PMID- 24658067
TI  - To the editor.

PMID- 24658068
TI  - J. Hutson replies.

PMID- 24658070
TI  - The alternative pathway of complement activation may be involved in the renal
      damage of human anti-glomerular basement membrane disease.
AB  - Linear deposition of IgG and complement 3 (C3) along glomerular basement membrane
      (GBM) is generally revealed in the kidneys of human anti-GBM disease. Our recent
      studies demonstrated the pathogenic role of complement activation in renal damage
      of this disease. However, the pathways of complement activation were still
      paradoxical. In this study, renal biopsy tissues from 10 patients with anti-GBM
      disease were used to investigate the pathways of complement activation by
      detecting the deposition of various complement components, including C1q, factor
      B, factor P (properdin), mannose-binding lectin (MBL), C3d, C4d and C5b-9, using
      immunohistochemistry and immunofluorescence. We found that C1q, factor B,
      properdin, C3d, C4d and C5b-9 were detected in all the glomeruli of our patients,
      along GBM with a linear and/or granular staining pattern. Furthermore, C1q,
      factor B and properdin co-localized well with C5b-9. The properdin also co
      localized well with C3d. However, the deposition of MBL was diffusive in
      mesangium, GBM, Bowman's capsule and within crescents and was not co-localized
      with C5b-9 but partially co-localized with C4d. The intensity of factor B
      deposition (3.3 vs. 1.2, P<0.001) and C5b-9 deposition (3.2 vs. 1.6, P<0.001) was
      significantly stronger in the glomeruli with crescent formation, compared with
      the glomeruli without crescents. The complement system is overall activated via
      both the alternative pathway and classical pathway in the kidneys of human anti
      GBM disease. The alternative pathway might play an important role in complement
      activation induced renal damage. 

PMID- 24658071
TI  - Efficient syntheses of pillar[6]arene-based hetero[4]rotaxanes using a
      cooperative capture strategy.
AB  - While a single pillar[6]arene ring, nestling between two cucurbit[6]uril rings in
      a series of three hetero[4]rotaxanes, is conformationally mobile in solution, it
      adopts the energetically most favourable conformation with local C3V symmetry in
      the solid state. 

PMID- 24658072
TI  - Light stimulates the mouse adrenal through a retinohypothalamic pathway
      independent of an effect on the clock in the suprachiasmatic nucleus.
AB  - The brain's master circadian pacemaker resides within the hypothalamic
      suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night
      cycle via the retinohypothalamic tract and the SCN provides temporal information
      to the central nervous system and to peripheral organs that function as secondary
      oscillators. The SCN clock-cell network is thought to be the hypothalamic link
      between the retina and descending autonomic circuits to peripheral organs such as
      the adrenal gland, thereby entraining those organs to the day/night cycle.
      However, there are at least three different routes or mechanisms by which retinal
      signals transmitted to the hypothalamus may be conveyed to peripheral organs: 1)
      via retinal input to SCN clock neurons; 2) via retinal input to non-clock neurons
      in the SCN; or 3) via retinal input to hypothalamic regions neighboring the SCN.
      It is very well documented that light-induced responses of the SCN clock (i.e.,
      clock gene expression, neural activity, and behavioral phase shifts) occur
      primarily during the subjective night. Thus to determine the role of the SCN
      clock in transmitting photic signals to descending autonomic circuits, we
      compared the phase dependency of light-evoked responses in the SCN and a
      peripheral oscillator, the adrenal gland. We observed light-evoked clock gene
      expression in the mouse adrenal throughout the subjective day and subjective
      night. Light also induced adrenal corticosterone secretion during both the
      subjective day and subjective night. The irradiance threshold for light-evoked
      adrenal responses was greater during the subjective day compared to the
      subjective night. These results suggest that retinohypothalamic signals may be
      relayed to the adrenal clock during the subjective day by a retinal pathway or
      cellular mechanism that is independent of an effect of light on the SCN neural
      clock network and thus may be important for the temporal integration of
      physiology and metabolism. 

PMID- 24658073
TI  - Recipient-related clinical risk factors for primary graft dysfunction after lung
      transplantation: a systematic review and meta-analysis.
AB  - BACKGROUND: Primary graft dysfunction (PGD) is the main cause of early morbidity
      and mortality after lung transplantation. Previous studies have yielded
      conflicting results for PGD risk factors. Herein, we carried out a systematic
      review and meta-analysis of published literature to identify recipient-related
      clinical risk factors associated with PGD development. METHOD: A systematic
      search of electronic databases (PubMed, Embase, Web of Science, Cochrane CENTRAL,
      and Scopus) for studies published from 1970 to 2013 was performed. Cohort, case
      control, or cross-sectional studies that examined recipient-related risk factors
      of PGD were included. The odds ratios (ORs) or mean differences (MDs) were
      calculated using random-effects models. RESULT: Thirteen studies involving 10042
      recipients met final inclusion criteria. From the pooled analyses, female gender
      (OR 1.38, 95% CI 1.09 to 1.75), African American (OR 1.82, 95%CI 1.36 to 2.45),
      idiopathic pulmonary fibrosis (IPF) (OR 1.78, 95% CI 1.49 to 2.13), sarcoidosis
      (OR 4.25, 95% CI 1.09 to 16.52), primary pulmonary hypertension (PPH) (OR 3.73,
      95%CI 2.16 to 6.46), elevated BMI (BMI>=25 kg/m2) (OR 1.83, 95% CI 1.26 to 2.64),
      and use of cardiopulmonary bypass (CPB) (OR 2.29, 95%CI 1.43 to 3.65) were
      significantly associated with increased risk of PGD. Age, cystic fibrosis,
      secondary pulmonary hypertension (SPH), intra-operative inhaled nitric oxide
      (NO), or lung transplant type (single or bilateral) were not significantly
      associated with PGD development (all P>0.05). Moreover, a nearly 4 fold increased
      risk of short-term mortality was observed in patients with PGD (OR 3.95, 95% CI
      2.80 to 5.57). CONCLUSIONS: Our analysis identified several recipient related
      risk factors for development of PGD. The identification of higher-risk recipients
      and further research into the underlying mechanisms may lead to selective
      therapies aimed at reducing this reperfusion injury.

PMID- 24658074
TI  - Clinical validation of the detection of KRAS and BRAF mutations from circulating
      tumor DNA.
AB  - Assessment of KRAS status is mandatory in patients with metastatic colorectal
      cancer (mCRC) before applying targeted therapy. We describe here a blinded
      prospective study to compare KRAS and BRAF mutation status data obtained from the
      analysis of tumor tissue by routine gold-standard methods and of plasma DNA using
      a quantitative PCR-based method specifically designed to analyze circulating cell
      free DNA (cfDNA). The mutation status was determined by both methods from 106
      patient samples. cfDNA analysis showed 100% specificity and sensitivity for the
      BRAF V600E mutation. For the seven tested KRAS point mutations, the method
      exhibited 98% specificity and 92% sensitivity with a concordance value of 96%.
      Mutation load, expressed as the proportion of mutant alleles in cfDNA, was highly
      variable (0.5-64.1%, median 10.5%) among mutated samples. CfDNA was detected in
      100% of patients with mCRC. This study shows that liquid biopsy through cfDNA
      analysis could advantageously replace tumor-section analysis and expand the scope
      of personalized medicine for patients with cancer. 

PMID- 24658075
TI  - Inverse agonist of estrogen-related receptor gamma controls Salmonella
      typhimurium infection by modulating host iron homeostasis.
AB  - In response to microbial infection, expression of the defensin-like peptide
      hepcidin (encoded by Hamp) is induced in hepatocytes to decrease iron release
      from macrophages. To elucidate the mechanism by which Salmonella enterica var.
      Typhimurium (S. typhimurium), an intramacrophage bacterium, alters host iron
      metabolism for its own survival, we examined the role of nuclear receptor family
      members belonging to the NR3B subfamily in mouse hepatocytes. Here, we report
      that estrogen-related receptor gamma (ERRgamma, encoded by Esrrg) modulates the
      intramacrophage proliferation of S. typhimurium by altering host iron
      homeostasis, and we demonstrate an antimicrobial effect of an ERRgamma inverse
      agonist. Hepatic ERRgamma expression was induced by S. typhimurium-stimulated
      interleukin-6 signaling, resulting in an induction of hepcidin and eventual
      hypoferremia in mice. Conversely, ablation of ERRgamma mRNA expression in liver
      attenuated the S. typhimurium-mediated induction of hepcidin and normalized the
      hypoferremia caused by S. typhimurium infection. An inverse agonist of ERRgamma
      ameliorated S. typhimurium-mediated hypoferremia through reduction of ERRgamma
      mediated hepcidin mRNA expression and exerted a potent antimicrobial effect on
      the S. typhimurium infection, thereby improving host survival. Taken together,
      these findings suggest an alternative approach to control multidrug-resistant
      intracellular bacteria by modulating host iron homeostasis. 

PMID- 24658076
TI  - New ex vivo approaches distinguish effective and ineffective single agents for
      reversing HIV-1 latency in vivo.
AB  - HIV-1 persists in a latent reservoir despite antiretroviral therapy (ART). This
      reservoir is the major barrier to HIV-1 eradication. Current approaches to
      purging the latent reservoir involve pharmacologic induction of HIV-1
      transcription and subsequent killing of infected cells by cytolytic T lymphocytes
      (CTLs) or viral cytopathic effects. Agents that reverse latency without
      activating T cells have been identified using in vitro models of latency.
      However, their effects on latently infected cells from infected individuals
      remain largely unknown. Using a new ex vivo assay, we demonstrate that none of
      the latency-reversing agents (LRAs) tested induced outgrowth of HIV-1 from the
      latent reservoir of patients on ART. Using a quantitative reverse transcription
      PCR assay specific for all HIV-1 mRNAs, we demonstrate that LRAs that do not
      cause T cell activation do not induce substantial increases in intracellular HIV
      1 mRNA in patient cells; only the protein kinase C agonist bryostatin-1 caused
      significant increases. These findings demonstrate that current in vitro models do
      not fully recapitulate mechanisms governing HIV-1 latency in vivo. Further, our
      data indicate that non-activating LRAs are unlikely to drive the elimination of
      the latent reservoir in vivo when administered individually. 

PMID- 24658077
TI  - An activin receptor IIA ligand trap corrects ineffective erythropoiesis in beta
      thalassemia.
AB  - The pathophysiology of ineffective erythropoiesis in beta-thalassemia is poorly
      understood. We report that RAP-011, an activin receptor IIA (ActRIIA) ligand
      trap, improved ineffective erythropoiesis, corrected anemia and limited iron
      overload in a mouse model of beta-thalassemia intermedia. Expression of growth
      differentiation factor 11 (GDF11), an ActRIIA ligand, was increased in splenic
      erythroblasts from thalassemic mice and in erythroblasts and sera from subjects
      with beta-thalassemia. Inactivation of GDF11 decreased oxidative stress and the
      amount of alpha-globin membrane precipitates, resulting in increased terminal
      erythroid differentiation. Abnormal GDF11 expression was dependent on reactive
      oxygen species, suggesting the existence of an autocrine amplification loop in
      beta-thalassemia. GDF11 inactivation also corrected the abnormal ratio of
      immature/mature erythroblasts by inducing apoptosis of immature erythroblasts
      through the Fas-Fas ligand pathway. Taken together, these observations suggest
      that ActRIIA ligand traps may have therapeutic relevance in beta-thalassemia by
      suppressing the deleterious effects of GDF11, a cytokine which blocks terminal
      erythroid maturation through an autocrine amplification loop involving oxidative
      stress and alpha-globin precipitation. 

PMID- 24658079
TI  - General synthesis of noble metal (Au, Ag, Pd, Pt) nanocrystal modified MoS2
      nanosheets and the enhanced catalytic activity of Pd-MoS2 for methanol oxidation.
AB  - A general and facile method for water-dispersed noble metal (Au, Ag, Pd, Pt)
      nanocrystal modified MoS2 nanosheets (NM-MoS2 NSs) has been developed. By using
      sodium carboxymethyl cellulose as a stabilizer, well-dispersed NM-MoS2 NSs with
      homogeneously deposited noble metal nanocrystals (NM NCs) can be synthesized in
      aqueous solutions. Due to the transition from the semiconducting 2H phase to the
      metallic 1T phase, the chemically exfoliated MoS2 (ce-MoS2) NSs have improved
      electrochemical activity. The partially metallic nature of the ce-MoS2 NSs and
      the catalytic activity of the NM NCs synergistically make NM-MoS2 NSs a potential
      electrochemical catalyst. For the first time, Pd-MoS2 NSs were used as an
      electrocatalyst for methanol oxidation in alkaline media. The results showed that
      Pd-MoS2 NSs have enhanced catalytic activity with 2.8-fold anodic peak current
      mass density compared to a commercial Pd/C catalyst, suggesting potential for
      application in direct methanol fuel cells (DMFCs). 

PMID- 24658078
TI  - Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia
      by promoting late-stage erythropoiesis.
AB  - Erythropoietin (EPO) stimulates proliferation of early-stage erythrocyte
      precursors and is widely used for the treatment of chronic anemia. However,
      several types of EPO-resistant anemia are characterized by defects in late-stage
      erythropoiesis, which is EPO independent. Here we investigated regulation of
      erythropoiesis using a ligand-trapping fusion protein (ACE-536) containing the
      extracellular domain of human activin receptor type IIB (ActRIIB) modified to
      reduce activin binding. ACE-536, or its mouse version RAP-536, produced rapid and
      robust increases in erythrocyte numbers in multiple species under basal
      conditions and reduced or prevented anemia in murine models. Unlike EPO, RAP-536
      promoted maturation of late-stage erythroid precursors in vivo. Cotreatment with
      ACE-536 and EPO produced a synergistic erythropoietic response. ACE-536 bound
      growth differentiation factor-11 (GDF11) and potently inhibited GDF11-mediated
      Smad2/3 signaling. GDF11 inhibited erythroid maturation in mice in vivo and ex
      vivo. Expression of GDF11 and ActRIIB in erythroid precursors decreased
      progressively with maturation, suggesting an inhibitory role for GDF11 in late
      stage erythroid differentiation. RAP-536 treatment also reduced Smad2/3
      activation, anemia, erythroid hyperplasia and ineffective erythropoiesis in a
      mouse model of myelodysplastic syndromes (MDS). These findings implicate
      transforming growth factor-beta (TGF-beta) superfamily signaling in erythroid
      maturation and identify ACE-536 as a new potential treatment for anemia,
      including that caused by ineffective erythropoiesis. 

PMID- 24658081
TI  - Posterior P1 and early frontal negativity reflect developmental changes in
      attentional distraction during adolescence.
AB  - Previous studies in adults have revealed that attentional distraction modulates
      the late positive potential (LPP) during emotion regulation. To determine whether
      early visual components reflect developmental changes in attentional distraction
      during adolescence, we collected event-related potentials from 20 young
      adolescents, 18 older adolescents, and 18 young adults as they performed a
      distraction task (counting) while viewing affective images. Consistent with
      previous findings obtained in distraction studies, the distraction task
      (counting) reduced emotional modulation of the LPP. At an early stage of
      processing, counting reduced emotional modulation of P1 and increased the
      negativity bias of early frontal negativity (eFN) for negatively valenced
      pictures compared to simple viewing with no distraction. sLORETA analyses further
      revealed eFN indexing of rostral prefrontal cortical activation, a cortical area
      that has been shown in recent fMRI studies to be activated by distraction.
      Moreover, P1 amplitudes in young and older adolescents did not differ but were
      both larger than the P1s in young adults. In addition, eFN amplitudes
      significantly decreased with age. The dissociable distraction patterns between
      the posterior P1 and eFN provide evidence not only for the timing hypothesis of
      emotion regulation but also for different developmental trajectories of visual
      processing areas and the prefrontal cortex during affective processing in
      adolescence. 

PMID- 24658080
TI  - Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which
      dynamically changes its oligomeric state.
AB  - Moyamoya disease is an idiopathic human cerebrovascular disorder that is
      characterized by progressive stenosis and abnormal collateral vessels. We
      recently identified mysterin/RNF213 as its first susceptibility gene, which
      encodes a 591-kDa protein containing enzymatically active P-loop ATPase and
      ubiquitin ligase domains and is involved in proper vascular development in
      zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+
      ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are
      known to generally mediate various biophysical and mechanical processes with the
      characteristic ring-shaped structure. Fluorescence correlation spectroscopy and
      biochemical evaluation suggested that mysterin dynamically changes its oligomeric
      forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease
      associated gene product is a unique protein that functions as ubiquitin ligase
      and AAA+ ATPase, which possibly contributes to vascular development through
      mechanical processes in the cell. 

PMID- 24658083
TI  - Morphology-, synthesis- and doping-independent tuning of ZnO work function using
      phenylphosphonates.
AB  - The work function (WF) of ZnO is modified by two types of dipole-bearing
      phenylphosphonate layers, yielding a maximum WF span of 1.2 eV. H3CO-phenyl
      phosphonate, with a positive dipole (positive pole pointing outwards from the
      surface), lowers the WF by ~350 meV. NC-phenyl phosphonate, with a negative
      dipole, increases the WF by ~750 meV. The WF shift is found to be independent of
      the type of ZnO surface. XPS data show strong molecular dipoles between the
      phenyl and the functionalizing (CN and OMe) tail groups, while an opposite dipole
      evolves in each molecular layer between the surface and the phenyl rings. The
      molecular modification is found to be invariant to supra-bandgap illumination,
      which indicates that the substrate's space charge-induced built-in potential is
      unlikely to be the reason for the WF difference. ZnO, grown by several different
      methods, with different degrees of crystalline perfection and various
      morphologies and crystallite dimensions, could all be modified to the same
      extent. Furthermore, a mixture of opposite dipoles allows gradual and continuous
      tuning of the WF, varying linearly with the partial concentration of the CN
      terminated phosphonate in the solution. Exposure to the phosphonic acids during
      the molecular layer deposition process erodes a few atomic layers of the ZnO. The
      general validity of the treatment and the fine-tuning of the WF of treated
      interfaces are of interest for solar cells and LED applications. 

PMID- 24658082
TI  - Contribution of p53 to metastasis.
AB  - The tumor suppressor p53 is lost or mutated in about half of all human cancers,
      and in those tumors in which it is wild-type, mechanisms exist to prevent its
      activation. p53 loss not only prevents incipient tumor cells from undergoing
      oncogene-induced senescence and apoptosis, but also perturbs cell-cycle
      checkpoints. This enables p53-deficient tumor cells with DNA damage to continue
      cycling, creating a permissive environment for the acquisition of additional
      mutations. Theoretically, this could contribute to the evolution of a cancer
      genome that is conducive to metastasis. Importantly, p53 loss also results in the
      disruption of pathways that inhibit metastasis, and transcriptionally defective
      TP53 mutants are known to gain additional functions that promote metastasis.
      Here, we review the evidence supporting a role for p53 loss or mutation in tumor
      metastasis, with an emphasis on breast cancer. SIGNIFICANCE: The metastatic
      potential of tumor cells can be positively infl uenced by loss of p53 or
      expression of p53 gain-of-function mutants. Understanding the mechanisms by which
      p53 loss and mutation promote tumor metastasis is crucial to understanding the
      biology of tumor progression and how to appropriately apply targeted therapies.

PMID- 24658084
TI  - Mismatch negativity of sad syllables is absent in patients with major depressive
      disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) is an important and highly prevalent
      mental disorder characterized by anhedonia and a lack of interest in everyday
      activities. Additionally, patients with MDD appear to have deficits in various
      cognitive abilities. Although a number of studies investigating the central
      auditory processing of low-level sound features in patients with MDD have
      demonstrated that this population exhibits impairments in automatic processing,
      the influence of emotional voice processing has yet to be addressed. To explore
      the automatic processing of emotional prosodies in patients with MDD, we analyzed
      the ability to detect automatic changes using event-related potentials (ERPs).
      METHOD: This study included 18 patients with MDD and 22 age- and sex-matched
      healthy controls. Subjects were instructed to watch a silent movie but to ignore
      the afferent acoustic emotional prosodies presented to both ears while continuous
      electroencephalographic activity was synchronously recorded. Prosodies included
      meaningless syllables, such as "dada" spoken with happy, angry, sad, or neutral
      tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak
      latency of the emotional differential waveforms were analyzed. RESULTS: The sad
      MMN was absent in patients with MDD, whereas the happy and angry MMN components
      were similar across groups. The abnormal sad emotional MMN component was not
      significantly correlated with the HRSD-17 and HAMA scores, respectively.
      CONCLUSION: The data indicate that patients with MDD are impaired in their
      ability to automatically process sad prosody, whereas their ability to process
      happy and angry prosodies remains normal. The dysfunctional sad emotion-related
      MMN in patients with MDD were not correlated with depression symptoms. The
      blunted MMN of sad prosodies could be considered a trait of MDD.

PMID- 24658086
TI  - Aspirin improves outcome in high risk prostate cancer patients treated with
      radiation therapy.
AB  - PURPOSE: High-risk prostate cancer (PC) has poor outcomes due to therapeutic
      resistance to conventional treatments, which include prostatectomy, radiation,
      and hormone therapy. Previous studies suggest that anticoagulant (AC) use may
      improve treatment outcomes in PC patients. We hypothesized that AC therapy
      confers a freedom from biochemical failure (FFBF) and overall survival (OS)
      benefit when administered with radiotherapy in patients with high-risk PC.
      MATERIALS AND METHODS: Analysis was performed on 74 high-risk PC patients who
      were treated with radiotherapy from 2005 to 2008 at UT Southwestern. Of these
      patients, 43 were on AC including aspirin (95.6%), clopidogrel (17.8%), warfarin
      (20%), and multiple ACs (31.1%). Associations between AC use and FFBF, OS,
      distant metastasis, and toxicity were analyzed. RESULTS: Median follow-up was
      56.6 mo for all patients. For patients taking any AC compared with no AC, there
      was improved FFBF at 5 years of 80% vs. 62% (P = 0.003), and for aspirin the FFBF
      was 84% vs. 65% (P = 0.008). Aspirin use was also associated with reduced rates
      of distant metastases at 5 years (12.2% vs. 26.7%, P = 0.039). On subset analysis
      of patients with Gleason score (GS) 9-10 histology, aspirin resulted in improved
      5-year OS (88% vs. 37%, P = 0.032), which remained significant on multivariable
      analysis (P<0.05). CONCLUSIONS: AC use was associated with a FFBF benefit in high
      risk PC which translated into an OS benefit in the highest risk PC patients with
      GS 9-10, who are most likely to experience mortality from PC. This hypothesis
      generating result suggests AC use may represent an opportunity to augment current
      therapy.

PMID- 24658085
TI  - Rapamycin downregulates thymidylate synthase and potentiates the activity of
      pemetrexed in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases, and
      almost half of newly diagnosed patients have metastatic disease. Pemetrexed is a
      widely used drug for NSCLC and inhibits several folate-dependent enzymes
      including thymidylate synthase (TS). Increased expression of TS confers
      resistance to pemetrexed in vitro and predicts poor response to pemetrexed.
      Rapamycin is an mTOR inhibitor and suppresses cap-dependent synthesis of specific
      mRNA species. Here, we show that the combination of rapamycin and pemetrexed
      synergistically inhibits proliferation of NSCLC cells. Although pemetrexed as a
      single agent induced TS, pretreatment with rapamycin suppressed pemetrexed
      induced TS expression. In vivo, the combination of rapamycin and pemetrexed
      inhibited growth of NSCLC xenografts, which correlated with decreased mTOR
      activity and suppression of pemetrexed-induced TS expression. The ability of
      rapamycin to enhance the efficacy of pemetrexed and prevent TS expression has
      implications for the design of Phase I and/or Phase II NSCLC clinical trials with
      mTOR inhibitors in combination with pemetrexed. 

PMID- 24658087
TI  - A mixture model for robust point matching under multi-layer motion.
AB  - This paper proposes an efficient mixture model for establishing robust point
      correspondences between two sets of points under multi-layer motion. Our
      algorithm starts by creating a set of putative correspondences which can contain
      a number of false correspondences, or outliers, in addition to the true
      correspondences (inliers). Next we solve for correspondence by interpolating a
      set of spatial transformations on the putative correspondence set based on a
      mixture model, which involves estimating a consensus of inlier points whose
      matching follows a non-parametric geometrical constraint. We formulate this as a
      maximum a posteriori (MAP) estimation of a Bayesian model with hidden/latent
      variables indicating whether matches in the putative set are outliers or inliers.
      We impose non-parametric geometrical constraints on the correspondence, as a
      prior distribution, in a reproducing kernel Hilbert space (RKHS). MAP estimation
      is performed by the EM algorithm which by also estimating the variance of the
      prior model (initialized to a large value) is able to obtain good estimates very
      quickly (e.g., avoiding many of the local minima inherent in this formulation).
      We further provide a fast implementation based on sparse approximation which can
      achieve a significant speed-up without much performance degradation. We
      illustrate the proposed method on 2D and 3D real images for sparse feature
      correspondence, as well as a public available dataset for shape matching. The
      quantitative results demonstrate that our method is robust to non-rigid
      deformation and multi-layer/large discontinuous motion. 

PMID- 24658088
TI  - Can a resident's publication record predict fellowship publications?
AB  - BACKGROUND: Internal medicine fellowship programs have an incentive to select
      fellows who will ultimately publish. Whether an applicant's publication record
      predicts long term publishing remains unknown. METHODS: Using records of
      fellowship bound internal medicine residents, we analyzed whether publications at
      time of fellowship application predict publications more than 3 years (2 years
      into fellowship) and up to 7 years after fellowship match. We calculate the
      sensitivity, specificity, positive and negative predictive values and likelihood
      ratios for every cutoff number of application publications, and plot a receiver
      operator characteristic curve of this test. RESULTS: Of 307 fellowship bound
      residents, 126 (41%) published at least one article 3 to 7 years after matching,
      and 181 (59%) of residents do not publish in this time period. The area under the
      receiver operator characteristic curve is 0.59. No cutoff value for application
      publications possessed adequate test characteristics. CONCLUSION: The number of
      publications an applicant has at time of fellowship application is a poor
      predictor of who publishes in the long term. These findings do not validate the
      practice of using application publications as a tool for selecting fellows.

PMID- 24658089
TI  - Effect of treatment of gestational diabetes mellitus: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To assess the efficacy and safety of treating pregnant women with
      gestational diabetes mellitus in comparison to usual antenatal care. METHODS: A
      systematic review and meta-analysis was conducted by including randomized
      controlled trials comparing any form of therapeutic intervention in comparison to
      usual antenatal care. A literature search was conducted using electronic
      databases together with a hand search of relevant journals and conference
      proceedings. RESULTS: Ten studies involving 3,881 patients contributed to meta
      analysis. Our results indicated that gestational diabetes mellitus treatment
      significantly reduced the risk for macrosomia (RR, 0.47; 95% CI, 0.38-0.57),
      large for gestational age births (RR, 0.55; 95% CI, 0.45-0.67), shoulder dystocia
      (RR, 0.42; 95% CI, 0.23-0.77) and gestational hypertension (RR, 0.68; 95% CI,
      0.53-0.87) without causing any significant increase in the risk for small for
      gestational age babies. However, no significant difference was observed between
      the two groups regarding perinatal/neonatal mortality, neonatal hypoglycemia,
      birth trauma, preterm births, pre-eclampsia, caesarean section and labor
      induction. CONCLUSION: Treating GDM reduces risk for many important adverse
      pregnancy outcomes and its association with any harm seems unlikely.

PMID- 24658092
TI  - DWI intensity values predict FLAIR lesions in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: In acute stroke, the DWI-FLAIR mismatch allows for the
      allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions,
      however, may be challenging to assess. In comparison, DWI may be a useful bio
      marker owing to high lesion contrast. We investigated the performance of a
      relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR
      lesions in acute stroke and analyzed its association with time-from-stroke-onset.
      METHODS: In a retrospective, dual-center MR-imaging study we included patients
      with acute stroke and time-from-stroke-onset <=12 hours (group A: n = 49, 1.5T;
      group B: n = 48, 3T). DW- and FLAIR-images were coregistered. The largest lesion
      extent in DWI defined the slice for further analysis. FLAIR-lesions were
      identified by 3 raters, delineated as regions-of-interest (ROIs) and copied on
      the DW-images. Circular ROIs were placed within the DWI-lesion and labeled
      according to the FLAIR-pattern (FLAIR+ or FLAIR-). ROI-values were normalized to
      the unaffected hemisphere. Adjusted and nonadjusted receiver-operating
      characteristics (ROC) curve analysis on patient level was performed to analyze
      the ability of a DWI- and ADC-rSI threshold to predict the presence of FLAIR
      lesions. Spearman correlation and adjusted linear regression analysis was
      performed to assess the relationship between DWI-intensity and time-from-stroke
      onset. RESULTS: DWI-rSI performed well in predicting lesions in FLAIR-imaging
      (mean area under the curve (AUC): group A: 0.84; group B: 0.85). An optimal mean
      DWI-rSI threshold was identified (A: 162%; B: 161%). ADC-maps performed worse
      (mean AUC: A: 0.58; B: 0.77). Adjusted regression models confirmed the superior
      performance of DWI-rSI. Correlation coefficents and linear regression showed a
      good association with time-from-stroke-onset for DWI-rSI, but not for ADC-rSI.
      CONCLUSION: An easily assessable DWI-rSI threshold identifies the presence of
      lesions in FLAIR-imaging with good accuracy and is associated with time-from
      stroke-onset in acute stroke. This finding underlines the potential of a DWI-rSI
      threshold as a marker of lesion age.

PMID- 24658090
TI  - Centrosome-kinase fusions promote oncogenic signaling and disrupt centrosome
      function in myeloproliferative neoplasms.
AB  - Chromosomal translocations observed in myeloproliferative neoplasms (MPNs)
      frequently fuse genes that encode centrosome proteins and tyrosine kinases. This
      causes constitutive activation of the kinase resulting in aberrant, proliferative
      signaling. The function of centrosome proteins in these fusions is not well
      understood. Among others, kinase centrosome localization and constitutive kinase
      dimerization are possible consequences of centrosome protein-kinase fusions. To
      test the relative contributions of localization and dimerization on kinase
      signaling, we targeted inducibly dimerizable FGFR1 to the centrosome and other
      subcellular locations and generated a mutant of the FOP-FGFR1 MPN fusion
      defective in centrosome localization. Expression in mammalian cells followed by
      western blot analysis revealed a significant decrease in kinase signaling upon
      loss of FOP-FGFR1 centrosome localization. Kinase dimerization alone resulted in
      phosphorylation of the FGFR1 signaling target PLCgamma, however levels comparable
      to FOP-FGFR1 required subcellular targeting in addition to kinase dimerization.
      Expression of MPN fusion proteins also resulted in centrosome disruption in
      epithelial cells and transformed patient cells. Primary human MPN cells showed
      masses of modified tubulin that colocalized with centrin, Smoothened (Smo),
      IFT88, and Arl13b. This is distinct from acute myeloid leukemia (AML) cells,
      which are not associated with centrosome-kinase fusions and had normal
      centrosomes. Our results suggest that effective proliferative MPN signaling
      requires both subcellular localization and dimerization of MPN kinases, both of
      which may be provided by centrosome protein fusion partners. Furthermore,
      centrosome disruption may contribute to the MPN transformation phenotype. 

PMID- 24658093
TI  - Pre-impact fall detection: optimal sensor positioning based on a machine learning
      paradigm.
AB  - The aim of this study was to identify the best subset of body segments that
      provides for a rapid and reliable detection of the transition from steady walking
      to a slipping event. Fifteen healthy young subjects managed unexpected
      perturbations during walking. Whole-body 3D kinematics was recorded and a machine
      learning algorithm was developed to detect perturbation events. In particular,
      the linear acceleration of all the body segments was parsed by Independent
      Component Analysis and a Neural Network was used to classify walking from
      unexpected perturbations. The Mean Detection Time (MDT) was 351+/-123 ms with an
      Accuracy of 95.4%. The procedure was repeated with data related to different
      subsets of all body segments whose variability appeared strongly influenced by
      the perturbation-induced dynamic modifications. Accordingly, feet and hands
      accounted for most data information and the performance of the algorithm were
      slightly reduced using their combination. Results support the hypothesis that, in
      the framework of the proposed approach, the information conveyed by all the body
      segments is redundant to achieve effective fall detection, and suitable
      performance can be obtained by simply observing the kinematics of upper and lower
      distal extremities. Future studies are required to assess the extent to which
      such results can be reproduced in older adults and in different experimental
      conditions. 

PMID- 24658094
TI  - Effective connectivity of hippocampal neural network and its alteration in Mg2+
      free epilepsy model.
AB  - Understanding the connectivity of the brain neural network and its evolution in
      epileptiform discharges is meaningful in the epilepsy researches and treatments.
      In the present study, epileptiform discharges were induced in rat hippocampal
      slices perfused with Mg2+-free artificial cerebrospinal fluid. The effective
      connectivity of the hippocampal neural network was studied by comparing the
      normal and epileptiform discharges recorded by a microelectrode array. The neural
      network connectivity was constructed by using partial directed coherence and
      analyzed by graph theory. The transition of the hippocampal network topology from
      control to epileptiform discharges was demonstrated. Firstly, differences existed
      in both the averaged in- and out-degree between nodes in the pyramidal cell layer
      and the granule cell layer, which indicated an information flow from the
      pyramidal cell layer to the granule cell layer during epileptiform discharges,
      whereas no consistent information flow was observed in control. Secondly, the
      neural network showed different small-worldness in the early, middle and late
      stages of the epileptiform discharges, whereas the control network did not show
      the small-world property. Thirdly, the network connectivity began to change
      earlier than the appearance of epileptiform discharges and lasted several seconds
      after the epileptiform discharges disappeared. These results revealed the
      important network bases underlying the transition from normal to epileptiform
      discharges in hippocampal slices. Additionally, this work indicated that the
      network analysis might provide a useful tool to evaluate the neural network and
      help to improve the prediction of seizures. 

PMID- 24658095
TI  - Cu binding by the Escherichia coli metal-efflux accessory protein RcnB.
AB  - Divalent cations play fundamental roles in biological systems where they act as
      structural and reactive determinants. Their high reactivity with biomolecules has
      forced living cells to evolve specific pathways for their in vivo handling. For
      instance the excess of metal can be expelled by dedicated efflux systems. The E.
      coli RcnA efflux pump expels both Ni and Co. This pump functions together with
      the periplasmic protein RcnB to maintain metal ion homeostasis. To gain insights
      into the efflux mechanism, metal binding properties of RcnB were investigated.
      Initial screening of metal ions by fluorescence quenching revealed Cu as a
      potential ligand for RcnB. Non-denaturing mass spectrometry and ITC experiments
      revealed the binding of one Cu ion per monomer with a micromolar affinity. This
      set of in vitro techniques was broadened by in vivo experiments that showed the
      accuracy of Cu binding by RcnB. RcnB implication in Cu detoxification was
      questioned and growth experiments as well as transcriptional analysis excluded a
      role for RcnB in Cu adaptation. Finally a mutant in a conserved methionine
      residue (Met86) displayed altered Cu binding. This mutant protein when tested for
      its Ni and Co resistance capacity was unable to complement an rcn mutant. Taken
      together these data show that RcnB is a new Cu-binding protein that is strikingly
      involved in a Ni/Co efflux system. 

PMID- 24658097
TI  - Beyond a climate-centric view of plant distribution: edaphic variables add value
      to distribution models.
AB  - Both climatic and edaphic conditions determine plant distribution, however many
      species distribution models do not include edaphic variables especially over
      large geographical extent. Using an exceptional database of vegetation plots (n =
      4839) covering an extent of ~55,000 km2, we tested whether the inclusion of fine
      scale edaphic variables would improve model predictions of plant distribution
      compared to models using only climate predictors. We also tested how well these
      edaphic variables could predict distribution on their own, to evaluate the
      assumption that at large extents, distribution is governed largely by climate. We
      also hypothesized that the relative contribution of edaphic and climatic data
      would vary among species depending on their growth forms and biogeographical
      attributes within the study area. We modelled 128 native plant species from
      diverse taxa using four statistical model types and three sets of abiotic
      predictors: climate, edaphic, and edaphic-climate. Model predictive accuracy and
      variable importance were compared among these models and for species'
      characteristics describing growth form, range boundaries within the study area,
      and prevalence. For many species both the climate-only and edaphic-only models
      performed well, however the edaphic-climate models generally performed best. The
      three sets of predictors differed in the spatial information provided about
      habitat suitability, with climate models able to distinguish range edges, but
      edaphic models able to better distinguish within-range variation. Model
      predictive accuracy was generally lower for species without a range boundary
      within the study area and for common species, but these effects were buffered by
      including both edaphic and climatic predictors. The relative importance of
      edaphic and climatic variables varied with growth forms, with trees being more
      related to climate whereas lower growth forms were more related to edaphic
      conditions. Our study identifies the potential for non-climate aspects of the
      environment to pose a constraint to range expansion under climate change.

PMID- 24658096
TI  - MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by
      activating the ERK/MAPK pathway.
AB  - Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non
      coding RNA (lncRNA), is associated with metastasis and is an independent
      prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1
      plays an important role in other malignancies. However, little is known about the
      role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of
      the biliary tract and has an extremely poor prognosis. In this study, we focused
      on the expression, biological functions and mechanism of MALAT1 in GBC and found
      that MALAT1 was significantly upregulated in GBC tissues compared with
      corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using
      lentivirus-mediated RNA interference significantly inhibited the proliferation
      and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK
      pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown.
      These results indicated that MALAT1 might serve as an oncogenic lncRNA that
      promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway. 

PMID- 24658100
TI  - An evaluation of comparability between NEISS and ICD-9-CM injury coding.
AB  - OBJECTIVE: To evaluate the National Electronic Injury Surveillance System's
      (NEISS) comparability with a data source that uses ICD-9-CM coding. METHODS: A
      sample of NEISS cases from a children's hospital in 2008 was selected, and cases
      were linked with their original medical record. Medical records were reviewed and
      an ICD-9-CM code was assigned to each case. Cases in the NEISS sample that were
      non-injuries by ICD-9-CM standards were identified. A bridging matrix between the
      NEISS and ICD-9-CM injury coding systems, by type of injury classification, was
      proposed and evaluated. RESULTS: Of the 2,890 cases reviewed, 13.32% (n = 385)
      were non-injuries according to the ICD-9-CM diagnosis. Using the proposed matrix,
      the comparability of the NEISS with ICD-9-CM coding was favorable among injury
      cases (kappa = 0.87, 95% CI: 0.85-0.88). The distribution of injury types among
      the entire sample was similar for the two systems, with percentage differences
      >=1% for only open wounds or amputation, poisoning, and other or unspecified
      injury types. CONCLUSIONS: There is potential for conducting comparable injury
      research using NEISS and ICD-9-CM data. Due to the inclusion of some non-injuries
      in the NEISS and some differences in type of injury definitions between NEISS and
      ICD-9-CM coding, best practice for studies using NEISS data obtained from the
      CPSC should include manual review of case narratives. Use of the standardized
      injury and injury type definitions presented in this study will facilitate more
      accurate comparisons in injury research.

PMID- 24658098
TI  - Wnt5a through noncanonical Wnt/JNK or Wnt/PKC signaling contributes to the
      differentiation of mesenchymal stem cells into type II alveolar epithelial cells
      in vitro.
AB  - The differentiation of mesenchymal stem cells (MSCs) into type II alveolar
      epithelial (AT II) cells is critical for reepithelization and recovery in acute
      respiratory distress syndrome (ARDS), and Wnt signaling was considered to be the
      underlying mechanisms. In our previous study, we found that canonical Wnt pathway
      promoted the differentiation of MSCs into AT II cells, however the role of the
      noncanonical Wnt pathway in this process is unclear. It was disclosed in this
      study that noncanonical Wnt signaling in mouse bone marrow-derived MSCs (mMSCs)
      was activated during the differentiation of mMSCs into AT II cells in a modified
      co-culture system with murine lung epithelial-12 cells and small airway growth
      media. The levels of surfactant protein (SP) C, SPB and SPD, the specific markers
      of AT II cells, increased in mMSCs when Wnt5a was added to activate noncanonical
      Wnt signaling, while pretreatment with JNK or PKC inhibitors reversed the
      promotion of Wnt5a. The differentiation rate of mMSCs also depends on their
      abilities to accumulate and survive in inflammatory tissue. We found that the
      Wnt5a supplement promoted the vertical and horizontal migration of mMSCs,
      ameliorated the cell death and the reduction of Bcl-2/Bax induced by H2O2. The
      effect of Wnt5a on the migration of mMSCs and their survival after H2O2 exposure
      were partially inhibited with PKC or JNK blockers. In conclusion, Wnt5a through
      Wnt/JNK signaling alone or both Wnt/JNK and Wnt/PKC signaling promoted the
      differentiation of mMSCs into AT II cells and the migration of mMSCs; through
      Wnt/PKC signaling, Wnt5a increased the survival of mMSCs after H2O2 exposure in
      vitro. 

PMID- 24658101
TI  - Nanomolar oxytocin synergizes with weak electrical afferent stimulation to
      activate the locomotor CpG of the rat spinal cord in vitro.
AB  - Synergizing the effect of afferent fibre stimulation with pharmacological
      interventions is a desirable goal to trigger spinal locomotor activity,
      especially after injury. Thus, to better understand the mechanisms to optimize
      this process, we studied the role of the neuropeptide oxytocin (previously shown
      to stimulate locomotor networks) on network and motoneuron properties using the
      isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 MUM) generated
      sporadic bursts with superimposed firing and dose-dependent depolarization. No
      desensitization was observed despite repeated applications. Tetrodotoxin
      completely blocked the effects of oxytocin, demonstrating the network origin of
      the responses. Recording motoneuron pool activity from lumbar ventral roots
      showed oxytocin mediated depolarization with synchronous bursts, and depression
      of reflex responses in a stimulus and peptide-concentration dependent fashion.
      Disinhibited bursting caused by strychnine and bicuculline was accelerated by
      oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive
      locomotion appeared when subthreshold concentrations of NMDA plus 5HT were
      coapplied with oxytocin, an effect prevented after 24 h incubation with the
      inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested,
      oxytocin did not change periodicity, although cycle amplitude became smaller. A
      novel protocol of electrical stimulation based on noisy waveforms and applied to
      one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus
      intensity was subthreshold, low doses of oxytocin triggered fictive locomotion
      although oxytocin per se did not affect primary afferent depolarization evoked by
      dorsal root pulses. Among the several functional targets for the action of
      oxytocin at lumbar spinal cord level, the present results highlight how small
      concentrations of this peptide could bring spinal networks to threshold for
      fictive locomotion in combination with other protocols, and delineate the use of
      oxytocin to strengthen the efficiency of electrical stimulation to activate
      locomotor circuits. 

PMID- 24658102
TI  - Ultrasound- versus palpation-guided injection of corticosteroid for plantar
      fasciitis: a meta-analysis.
AB  - BACKGROUND: It is controversial whether ultrasound-guided injection of
      corticosteroid is superior to palpation-guided injection for plantar fasciitis.
      This meta-analysis was performed to compare the effectiveness of ultrasound
      guided and palpation-guided injection of corticosteroid for the treatment of
      plantar fasciitis. METHODS: Databases (MEDLINE, Cochrane library and EMBASE) and
      reference lists were searched from their establishment to August 30, 2013 for
      randomized controlled trials (RCTs) comparing ultrasound-guided with palpation
      guided injection for plantar fasciitis. The Cochrane risk of bias (ROB) tool was
      used to assess the methodological quality. Outcome measurements were visual
      analogue scale (VAS), tenderness threshold (TT), heel tenderness index (HTI),
      response rate, plantar fascia thickness (PFT), hypoechogenicity and heel pad
      thickness (HPT). The statistical analysis was performed with software RevMan 5.2
      and Stata 12.0. When I2<50%, the fixed-effects model was adopted. Otherwise the
      randomized-effects model was adopted. The Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) system was used to assess the quality of
      evidence. RESULTS: Five RCTs with 149 patients were identified and analyzed.
      Compared with palpation-guided injection, ultrasound-guided injection was
      superior with regard to VAS, TT, response rate, PFT and hypoechogenicity.
      However, there was no statistical significance between the two groups for HPT and
      HTI. CONCLUSION: Ultrasound-guided injection of corticosteroid tends to be more
      effective than palpation-guided injection. However, it needs to be confirmed by
      further research.

PMID- 24658103
TI  - Pregnancy differentially impacts performance of latent tuberculosis diagnostics
      in a high-burden setting.
AB  - BACKGROUND: Targeted screening for latent TB infection (LTBI) in vulnerable
      populations is a recommended TB control strategy. Pregnant women are at high risk
      for developing TB and likely to access healthcare, making pregnancy an important
      screening opportunity in developing countries. The sensitivity of the widely-used
      tuberculin skin test (TST), however, may be reduced during pregnancy. METHODS: We
      performed a cross-sectional study comparing the TST with the QuantiFERON Gold In
      tube (QGIT) in 401 HIV-negative women presenting antepartum (n = 154), at
      delivery (n = 148), or postpartum (n = 99) to a government hospital in Pune,
      India. A subset of 60 women enrolled during pregnancy was followed longitudinally
      and received both tests at all three stages of pregnancy. RESULTS: The QGIT
      returned significantly more positive results than the TST. Of the 401 women in
      the cross-sectional study, 150 (37%) had a positive QGIT, compared to 59 (14%)
      for the TST (p<0.005). Forty-nine (12%) did not have their TST read. Of 356 who
      had both results available, 46 (13%) were concordant positive, 91 (25%) were
      discordant (12 (3%) TST+/QGIT-; 79 (22%) TST-/QGIT+), and 206 (57%) concordant
      negative. Comparison by stage of pregnancy revealed that QGIT percent positivity
      remained stable between antepartum and delivery, unlike TST results (QGIT 31-32%
      vs TST 11-17%). Median IFN-gamma concentration was lower at delivery than in
      antepartum or postpartum (1.66 vs 2.65 vs 8.99 IU/mL, p = 0.001). During
      postpartum, both tests had significantly increased positives (QGIT 31% vs 32% vs
      52%, p = 0.01; TST 17% vs 11% vs 25%, p<0.005). The same trends were observed in
      the longitudinal subset. CONCLUSIONS: Timing and choice of LTBI test during
      pregnancy impact results. QGIT was more stable and more closely approximated the
      LTBI prevalence in India. But pregnancy stage clearly affects both tests, raising
      important questions about how the complex immune changes brought on by pregnancy
      may impact LTBI screening.

PMID- 24658104
TI  - Removal and fate of micropollutants in a sponge-based moving bed bioreactor.
AB  - This study investigated the removal of micropollutants using polyurethane sponge
      as attached-growth carrier. Batch experiments demonstrated that micropollutants
      could adsorb to non-acclimatized sponge cubes to varying extents. Acclimatized
      sponge showed significantly enhanced removal of some less hydrophobic compounds
      (log D<2.5), such as ibuprofen, acetaminophen, naproxen, and estriol, as compared
      with non-acclimatized sponge. The results for bench-scale sponge-based moving bed
      bioreactor (MBBR) system elucidated compound-specific variation in removal,
      ranging from 25.9% (carbamazepine) to 96.8% (beta-Estradiol 17-acetate) on
      average. In the MBBR system, biodegradation served as a major removal pathway for
      most compounds. However, sorption to sludge phase was also a notable removal
      mechanism of some persistent micropollutants. Particularly, carbamazepine,
      ketoprofen and pentachlorophenol were found at high concentrations (7.87, 6.05
      and 5.55 MUg/g, respectively) on suspended biosolids. As a whole, the
      effectiveness of MBBR for micropollutant removal was comparable with those of
      activated sludge processes and MBRs.

PMID- 24658105
TI  - Models construction for acetone-butanol-ethanol fermentations with
      acetate/butyrate consecutively feeding by graph theory.
AB  - Several fermentations with consecutively feeding of acetate/butyrate were
      conducted in a 7 L fermentor and the results indicated that exogenous
      acetate/butyrate enhanced solvents productivities by 47.1% and 39.2%
      respectively, and changed butyrate/acetate ratios greatly. Then extracellular
      butyrate/acetate ratios were utilized for calculation of acids rates and the
      results revealed that acetate and butyrate formation pathways were almost blocked
      by corresponding acids feeding. In addition, models for acetate/butyrate feeding
      fermentations were constructed by graph theory based on calculation results and
      relevant reports. Solvents concentrations and butanol/acetone ratios of these
      fermentations were also calculated and the results of models calculation matched
      fermentation data accurately which demonstrated that models were constructed in a
      reasonable way.

PMID- 24658106
TI  - Improving Gluconobacter oxydans performance in the in situ removal of the
      inhibitor for asymmetric resolution of racemic 1-phenyl-1,2-ethanediol.
AB  - Gluconobacter oxydans DSM2003 was used to catalyze the oxidation of racemic 1
      phenyl-1,2-ethanediol (PED) for the production of (S)-enantiomer. The oxidative
      product mandelic acid produced strong inhibition to this reaction and largely
      reduced the activity of biocatalyst, which was the key problem in the reaction.
      In order to overcome this bottleneck, an anion exchange resin was selected and
      introduced as adsorbent for the in situ removal of the inhibitor from the
      reaction system. This method increased the substrate concentration from 12 to 60
      g/L and the yield of (S)-PED by approximately five times from 4.9 g/L, on the
      premise that the enantiomeric excess (ee) value of (S)-PED remained above 96% and
      the reaction time was no more than 20 h. Moreover, the final space-time yield was
      over 1.2g/L/h, which was higher than that reported from previous studies.

PMID- 24658107
TI  - A novel membrane distillation-thermophilic bioreactor system: biological
      stability and trace organic compound removal.
AB  - The removal of trace organic compounds (TrOCs) by a novel membrane distillation
      thermophilic bioreactor (MDBR) system was examined. Salinity build-up and the
      thermophilic conditions to some extent adversely impacted the performance of the
      bioreactor, particularly the removal of total nitrogen and recalcitrant TrOCs.
      While most TrOCs were well removed by the thermophilic bioreactor, compounds
      containing electron withdrawing functional groups in their molecular structure
      were recalcitrant to biological treatment and their removal efficiency by the
      thermophilic bioreactor was low (0-53%). However, the overall performance of the
      novel MDBR system with respect to the removal of total organic carbon, total
      nitrogen, and TrOCs was high and was not significantly affected by the conditions
      of the bioreactor. All TrOCs investigated here were highly removed (>95%) by the
      MDBR system. Biodegradation, sludge adsorption, and rejection by MD contribute to
      the removal of TrOCs by MDBR treatment. 

PMID- 24658108
TI  - Red light represses the photophysiology of the scleractinian coral Stylophora
      pistillata.
AB  - Light spectrum plays a key role in the biology of symbiotic corals, with blue
      light resulting in higher coral growth, zooxanthellae density, chlorophyll a
      content and photosynthesis rates as compared to red light. However, it is still
      unclear whether these physiological processes are blue-enhanced or red-repressed.
      This study investigated the individual and combined effects of blue and red light
      on the health, zooxanthellae density, photophysiology and colouration of the
      scleractinian coral Stylophora pistillata over 6 weeks. Coral fragments were
      exposed to blue, red, and combined 50/50% blue red light, at two irradiance
      levels (128 and 256 MUmol m(-2) s(-1)). Light spectrum affected the
      health/survival, zooxanthellae density, and NDVI (a proxy for chlorophyll a
      content) of S. pistillata. Blue light resulted in highest survival rates, whereas
      red light resulted in low survival at 256 MUmol m(-2) s(-1). Blue light also
      resulted in higher zooxanthellae densities compared to red light at 256 MUmol m(
      2) s(-1), and a higher NDVI compared to red and combined blue red light. Overall,
      our results suggest that red light negatively affects the health, survival,
      symbiont density and NDVI of S. pistillata, with a dominance of red over blue
      light for NDVI.

PMID- 24658110
TI  - Introduction: Orthopaedic Trauma Association Basic Science Focus Forum 2012.

PMID- 24658109
TI  - Multiple lesions in receptor tyrosine kinase pathway determine glioblastoma
      response to pan-ERBB inhibitor PF-00299804 and PI3K/mTOR dual inhibitor PF
      05212384.
AB  - A novel pan ERBB inhibitor PF-00299804 (dacomitinib) is currently in phase II
      clinical trials in glioblastoma multiforme (GBM) patients; however its pre
      clinical efficacy in GBMs has not been tested. In this study, we evaluated the
      efficacy of dacomitinib alone or in combination with PI3K/mTOR dual inhibitor PF
      05212384 in GBM and assessed the mechanisms of resistance and the molecular
      determinants of response. A panel of established and patient derived primary GBM
      lines that present different molecular profiles and also the GBM lines engineered
      to express EGFRvIII mutant or PTEN were treated with either dacomitinib, PF
      05212384, or combination and assessed for their viability and changes in
      EGFR/PI3K/mTOR signaling. We show that dacomitinib significantly reduced
      phosphorylated EGFR in all the GBM lines but did not show a dose-dependent
      response on cell viability in a majority of the lines tested. Multiple lesions in
      the receptor tyrosine kinases (RTKs) pathway including PTEN mutation, co
      activation of RTKs, and EGFRvIII mutation resulted in unaltered active status of
      PI3K/mTOR in the GBM lines even in the presence of EGFR inhibition. Blocking
      PI3K/mTOR dramatically inhibited cell proliferation in most GBM lines and
      enhanced dacomitinib induction of apoptosis in a GBM line that has both EGFR
      amplification and EGFR-independent PI3K activation. These data suggest molecular
      profiling of EGFR/PI3K/PTEN status to select GBM patients for EGFR or/and
      PI3K/mTOR targeted therapies. 

PMID- 24658111
TI  - Microfluidic-enabled liposomes elucidate size-dependent transdermal transport.
AB  - Microfluidic synthesis of small and nearly-monodisperse liposomes is used to
      investigate the size-dependent passive transdermal transport of nanoscale lipid
      vesicles. While large liposomes with diameters above 105 nm are found to be
      excluded from deeper skin layers past the stratum corneum, the primary barrier to
      nanoparticle transport, liposomes with mean diameters between 31-41 nm exhibit
      significantly enhanced penetration. Furthermore, multicolor fluorescence imaging
      reveals that the smaller liposomes pass rapidly through the stratum corneum
      without vesicle rupture. These findings reveal that nanoscale liposomes with well
      controlled size and minimal size variance are excellent vehicles for transdermal
      delivery of functional nanoparticle drugs. 

PMID- 24658112
TI  - The pleasantness of visual symmetry: always, never or sometimes.
AB  - There is evidence of a preference for visual symmetry. This is true from mate
      selection in the animal world to the aesthetic appreciation of works of art. It
      has been proposed that this preference is due to processing fluency, which
      engenders positive affect. But is visual symmetry pleasant? Evidence is mixed as
      explicit preferences show that this is the case. In contrast, implicit measures
      show that visual symmetry does not spontaneously engender positive affect but it
      depends on participants intentionally assessing visual regularities. In four
      experiments using variants of the affective priming paradigm, we investigated
      when visual symmetry engenders positive affect. Findings showed that, when no
      Stroop-like effects or post-lexical mechanisms enter into play, visual symmetry
      spontaneously elicits positive affect and results in affective congruence
      effects. 

PMID- 24658113
TI  - EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by
      amyloid-beta oligomers.
AB  - The early stages of Alzheimer's disease are characterised by impaired synaptic
      plasticity and synapse loss. Here, we show that amyloid-beta oligomers (AbetaOs)
      activate the c-Abl kinase in dendritic spines of cultured hippocampal neurons and
      that c-Abl kinase activity is required for AbetaOs-induced synaptic loss. We also
      show that the EphA4 receptor tyrosine kinase is upstream of c-Abl activation by
      AbetaOs. EphA4 tyrosine phosphorylation (activation) is increased in cultured
      neurons and synaptoneurosomes exposed to AbetaOs, and in Alzheimer-transgenic
      mice brain. We do not detect c-Abl activation in EphA4-knockout neurons exposed
      to AbetaOs. More interestingly, we demonstrate EphA4/c-Abl activation is a key
      signalling event that mediates the synaptic damage induced by AbetaOs. According
      to this results, the EphA4 antagonistic peptide KYL and c-Abl inhibitor STI
      prevented i) dendritic spine reduction, ii) the blocking of LTP induction and
      iii) neuronal apoptosis caused by AbetaOs. Moreover, EphA4-/- neurons or sh-EphA4
      transfected neurons showed reduced synaptotoxicity by AbetaOs. Our results are
      consistent with EphA4 being a novel receptor that mediates synaptic damage
      induced by AbetaOs. EphA4/c-Abl signalling could be a relevant pathway involved
      in the early cognitive decline observed in Alzheimer's disease patients. 

PMID- 24658115
TI  - Topological surface state in the Kondo insulator samarium hexaboride.
AB  - Topological invariants of electron wavefunctions in condensed matter reveal many
      intriguing phenomena. A notable example is provided by topological insulators,
      which are characterized by an insulating bulk coexisting with a metallic boundary
      state. Although there has been intense interest in Bi-based topological
      insulators, their behaviour is complicated by the presence of a considerable
      residual bulk conductivity. Theories predict that the Kondo insulator system
      SmB6, which is known to undergo a transition from a Kondo lattice metal to a
      small-gap insulator state with decreasing temperature, could be a topological
      insulator. Although the insulating bulk and metallic surface separation has been
      demonstrated in recent transport measurements, these have not demonstrated the
      topologically protected nature of the metallic surface state. Here we report
      thickness-dependent transport measurements on doped SmB6, and show that magnetic
      and non-magnetic doping results in contrasting behaviour that supports the
      conclusion that SmB6 shows virtually no residual bulk conductivity. 

PMID- 24658114
TI  - Synthesis and patterning of tunable multiscale materials with engineered cells.
AB  - Many natural biological systems--such as biofilms, shells and skeletal tissues-
      are able to assemble multifunctional and environmentally responsive multiscale
      assemblies of living and non-living components. Here, by using inducible genetic
      circuits and cellular communication circuits to regulate Escherichia coli curli
      amyloid production, we show that E. coli cells can organize self-assembling
      amyloid fibrils across multiple length scales, producing amyloid-based materials
      that are either externally controllable or undergo autonomous patterning. We also
      interfaced curli fibrils with inorganic materials, such as gold nanoparticles
      (AuNPs) and quantum dots (QDs), and used these capabilities to create an
      environmentally responsive biofilm-based electrical switch, produce gold
      nanowires and nanorods, co-localize AuNPs with CdTe/CdS QDs to modulate QD
      fluorescence lifetimes, and nucleate the formation of fluorescent ZnS QDs. This
      work lays a foundation for synthesizing, patterning, and controlling functional
      composite materials with engineered cells.

PMID- 24658116
TI  - Persistent optically induced magnetism in oxygen-deficient strontium titanate.
AB  - Strontium titanate (SrTiO3) is a foundational material in the emerging field of
      complex oxide electronics. Although its bulk electronic and optical properties
      are rich and have been studied for decades, SrTiO3 has recently become a renewed
      focus of materials research catalysed in part by the discovery of
      superconductivity and magnetism at interfaces between SrTiO3 and other non
      magnetic oxides. Here we illustrate a new aspect to the phenomenology of
      magnetism in SrTiO3 by reporting the observation of an optically induced and
      persistent magnetization in slightly oxygen-deficient bulk SrTiO3-delta crystals
      using magnetic circular dichroism (MCD) spectroscopy and SQUID magnetometry. This
      zero-field magnetization appears below ~18 K, persists for hours below 10 K, and
      is tunable by means of the polarization and wavelength of sub-bandgap (400-500
      nm) light. These effects occur only in crystals containing oxygen vacancies,
      revealing a detailed interplay between magnetism, lattice defects, and light in
      an archetypal complex oxide material. 

PMID- 24658117
TI  - Strong, tough and stiff bioinspired ceramics from brittle constituents.
AB  - High strength and high toughness are usually mutually exclusive in engineering
      materials. In ceramics, improving toughness usually relies on the introduction of
      a metallic or polymeric ductile phase, but this decreases the material's strength
      and stiffness as well as its high-temperature stability. Although natural
      materials that are both strong and tough rely on a combination of mechanisms
      operating at different length scales, the relevant structures have been extremely
      difficult to replicate. Here, we report a bioinspired approach based on
      widespread ceramic processing techniques for the fabrication of bulk ceramics
      without a ductile phase and with a unique combination of high strength (470 MPa),
      high toughness (22 MPa m(1/2)), and high stiffness (290 GPa). Because only
      mineral constituents are needed, these ceramics retain their mechanical
      properties at high temperatures (600  degrees C). Our bioinspired, material
      independent approach should find uses in the design and processing of materials
      for structural, transportation and energy-related applications. 

PMID- 24658118
TI  - Protection against dengue virus infection in mice by administration of antibodies
      against modified nonstructural protein 1.
AB  - BACKGROUND: Infection with dengue virus (DENV) may cause life-threatening disease
      with thrombocytopenia and vascular leakage which are related to dysfunction of
      platelets and endothelial cells. We previously showed that antibodies (Abs)
      against DENV nonstructural protein 1 (NS1) cross-react with human platelets and
      endothelial cells, leading to functional disturbances. Based on sequence homology
      analysis, the C-terminal region of DENV NS1 protein contains cross-reactive
      epitopes. For safety in vaccine development, the cross-reactive epitopes of DENV
      NS1 protein should be deleted or modified. METHODOLOGY/PRINCIPAL FINDINGS: We
      tested the protective effects of Abs against full-length DENV NS1, NS1 lacking
      the C-terminal amino acids (a.a.) 271-352 (designated DeltaC NS1), and chimeric
      DJ NS1 consisting of N-terminal DENV NS1 (a.a. 1-270) and C-terminal Japanese
      encephalitis virus NS1 (a.a. 271-352). The anti-DeltaC NS1 and anti-DJ NS1 Abs
      showed a lower binding activity to endothelial cells and platelets than that of
      anti-DENV NS1 Abs. Passive immunization with anti-DeltaC NS1 and anti-DJ NS1 Abs
      reduced DENV-induced prolonged mouse tail bleeding time. Treatment with anti-DENV
      NS1, anti-DeltaC NS1 and anti-DJ NS1 Abs reduced local skin hemorrhage,
      controlled the viral load of DENV infection in vivo, synergized with complement
      to inhibit viral replication in vitro, as well as abolished DENV-induced
      macrophage infiltration to the site of skin inoculation. Moreover, active
      immunization with modified NS1 protein, but not with unmodified DENV NS1 protein,
      reduced DENV-induced prolonged bleeding time, local skin hemorrhage, and viral
      load. CONCLUSIONS/SIGNIFICANCE: These results support the idea that modified NS1
      proteins may represent an improved strategy for safe and effective vaccine
      development against DENV infection.

PMID- 24658119
TI  - 3-Methylcholanthrene, an AhR agonist, caused cell-cycle arrest by histone
      deacetylation through a RhoA-dependent recruitment of HDAC1 and pRb2 to E2F1
      complex.
AB  - We previously showed that treating vascular endothelial cells with 3
      methylcholanthrene (3MC) caused cell-cycle arrest in the Go/G1 phase; this
      resulted from the induction of p21 and p27 and a decreased level and activity of
      the cyclin-dependent kinase, Cdk2. We further investigated the molecular
      mechanisms that modulate cell-cycle regulatory proteins through the aryl
      hydrocarbon receptor (AhR)/Ras homolog gene family, member A (RhoA) dependent
      epigenetic modification of histone. AhR/RhoA activation mediated by 3MC was
      essential for the upregulation of retinoblastoma 2 (pRb2) and histone deacetylase
      1 (HDAC1), whereas their nuclear translocation was primarily modulated by RhoA
      activation. The combination of increased phosphatase and tensin homolog (PTEN)
      activity and decreased phosphatidylinositide 3-kinase (PI3K) activation by 3MC
      led to the inactivation of the Ras-cRaf pathway, which contributed to pRb2
      hypophosphorylation. Increased HDAC1/pRb2 recruitment to the E2F1 complex
      decreased E2F1-transactivational activity and H3/H4 deacetylation, resulting in
      the downregulation of cell-cycle regulatory proteins (Cdk2/4 and Cyclin D3/E). Co
      immunoprecipitation and electrophoretic mobility shift assay (EMSA) results
      showed that simvastatin prevented the 3MC-increased binding activities of E2F1
      proteins in their promoter regions. Additionally, RhoA inhibitors (statins)
      reversed the effect of 3MC in inhibiting DNA synthesis by decreasing the nuclear
      translocation of pRb2/HDAC1, leading to a recovery of the levels of cell-cycle
      regulatory proteins. In summary, 3MC decreased cell proliferation by the
      epigenetic modification of histone through an AhR/RhoA-dependent mechanism that
      can be rescued by statins. 

PMID- 24658120
TI  - Selective hydrophilic modification of Parylene C films: a new approach to cell
      micro-patterning for synthetic biology applications.
AB  - We demonstrate a simple, accurate and versatile method to manipulate Parylene C,
      a material widely known for its high biocompatibility, and transform it to a
      substrate that can effectively control the cellular microenvironment and
      consequently affect the morphology and function of the cells in vitro. The
      Parylene C scaffolds are fabricated by selectively increasing the material's
      surface water affinity through lithography and oxygen plasma treatment, providing
      free bonds for attachment of hydrophilic biomolecules. The micro-engineered
      constructs were tested as culture scaffolds for rat ventricular fibroblasts and
      neonatal myocytes (NRVM), toward modeling the unique anisotropic architecture of
      native cardiac tissue. The scaffolds induced the patterning of extracellular
      matrix compounds and therefore of the cells, which demonstrated substantial
      alignment compared to typical unstructured cultures. Ca(2+) cycling properties of
      the NRVM measured at rates of stimulation 0.5-2 Hz were significantly modified
      with a shorter time to peak and time to 90% decay, and a larger fluorescence
      amplitude (p < 0.001). The proposed technique is compatible with standard cell
      culturing protocols and exhibits long-term pattern durability. Moreover, it
      allows the integration of monitoring modalities into the micro-engineered
      substrates for a comprehensive interrogation of physiological parameters. 

PMID- 24658121
TI  - Arabidopsis ATG4 cysteine proteases specificity toward ATG8 substrates.
AB  - Macroautophagy (hereafter autophagy) is a regulated intracellular process during
      which cytoplasmic cargo engulfed by double-membrane autophagosomes is delivered
      to the vacuole or lysosome for degradation and recycling. Atg8 that is conjugated
      to phosphatidylethanolamine (PE) during autophagy plays an important role not
      only in autophagosome biogenesis but also in cargo recruitment. Conjugation of PE
      to Atg8 requires processing of the C-terminal conserved glycine residue in Atg8
      by the Atg4 cysteine protease. The Arabidopsis plant genome contains 9 Atg8
      (AtATG8a to AtATG8i) and 2 Atg4 (AtATG4a and AtATG4b) family members. To
      understand AtATG4's specificity toward different AtATG8 substrates, we generated
      a unique synthetic substrate C-AtATG8-ShR (citrine-AtATG8-Renilla luciferase
      SuperhRLUC). In vitro analyses indicated that AtATG4a is catalytically more
      active and has broad AtATG8 substrate specificity compared with AtATG4b.
      Arabidopsis transgenic plants expressing the synthetic substrate C-AtAtg8a-ShR is
      efficiently processed by endogenous AtATG4s and targeted to the vacuole during
      nitrogen starvation. These results indicate that the synthetic substrate mimics
      endogenous AtATG8, and its processing can be monitored in vivo by a
      bioluminescence resonance energy transfer (BRET) assay. The synthetic Atg8
      substrates provide an easy and versatile method to study plant autophagy during
      different biological processes.

PMID- 24658122
TI  - Effects of flow-induced shear stress on limbal epithelial stem cell growth and
      enrichment.
AB  - The roles of limbal epithelial stem cells (LESCs) are widely recognized, but for
      these cells to be utilized in basic research and potential clinical applications,
      researchers must be able to efficiently isolate them and subsequently maintain
      their stemness in vitro. We aimed to develop a biomimetic environment for LESCs
      involving cells from their in vivo niche and the principle of flow-induced shear
      stress, and to subsequently demonstrate the potential of this novel paradigm.
      LESCs, together with neighboring cells, were isolated from the minced limbal
      tissues of rabbits. At days 8 and 9 of culture, the cells were exposed to a
      steady flow or intermittent flow for 2 h per day in a custom-designed bioreactor.
      The responses of LESCs and epithelial cells were assessed at days 12 and 14.
      LESCs and epithelial cells responded to both types of flow. Proliferation of
      LESCs, as assessed using a BrdU assay, was increased to a greater extent under
      steady flow conditions. Holoclones were found under intermittent flow, indicating
      that differentiation into transient amplifying cells had occurred.
      Immunofluorescent staining of Bmi-1 suggested that steady flow has a positive
      effect on the maintenance of stemness. This finding was confirmed by real-time
      PCR. Notch-1 and p63 were more sensitive to intermittent flow, but this effect
      was transient. K3 and K12 expression, indicative of differentiation of LESCs into
      epithelial cells, was induced by flow and lasted longer under intermittent flow
      conditions. In summary, culture of LESCs in a bioreactor under a steady flow
      paradigm, rather than one of intermittent flow, is beneficial for both increasing
      proliferation and maintaining stemness. Conversely, intermittent flow appears to
      induce differentiation of LESCs. This novel experimental method introduces micro
      mechanical stimuli to traditional culture techniques, and has potential for
      regulating the proliferation and differentiation of LESCs in vitro, thereby
      facilitating research in this field. 

PMID- 24658124
TI  - Patterns and predictors of self-medication in northern Uganda.
AB  - Self-medication with antimicrobial agents is a common form of self-care among
      patients globally with the prevalence and nature differing from country to
      country. Here we assessed the prevalence and predictors of antimicrobial self
      medication in post-conflict northern Uganda. A cross-sectional study was carried
      out using structured interviews on 892 adult (>=18 years) participants.
      Information on drug name, prescriber, source, cost, quantity of drug obtained,
      and drug use was collected. Households were randomly selected using multistage
      cluster sampling method. One respondent who reported having an illness within
      three months in each household was recruited. In each household, information was
      obtained from only one adult individual. Data was analyzed using STATA at 95%
      level of significance. The study found that a high proportion (75.7%) of the
      respondents practiced antimicrobial self-medication. Fever, headache, lack of
      appetite and body weakness were the disease symptoms most treated through self
      medication (30.3%). The commonly self-medicated antimicrobials were coartem
      (27.3%), amoxicillin (21.7%), metronidazole (12.3%), and cotrimoxazole (11.6%).
      Drug use among respondents was mainly initiated by self-prescription (46.5%) and
      drug shop attendants (57.6%). On average, participants obtained 13.9+/-8.8
      (95%CI: 12.6-13.8) tablets/capsules of antimicrobial drugs from drug shops and
      drugs were used for an average of 3.7+/-2.8 days (95%CI: 3.3-3.5). Over half
      (68.2%) of the respondents would recommend self-medication to another sick
      person. A high proportion (76%) of respondents reported that antimicrobial self
      medication had associated risks such as wastage of money (42.1%), drug resistance
      (33.2%), and masking symptoms of underlying disease (15.5%). Predictors of self
      medication with antimicrobial agents included gender, drug knowledge, drug
      leaflets, advice from friends, previous experience, long waiting time, and
      distance to the health facility. Despite knowledge of associated risks, use of
      self-medication with antimicrobial drugs in management of disease symptoms is a
      common practice in post-conflict northern Uganda. 

PMID- 24658123
TI  - NDK-1, the homolog of NM23-H1/H2 regulates cell migration and apoptotic
      engulfment in C. elegans.
AB  - Abnormal regulation of cell migration and altered rearrangement of cytoskeleton
      are characteristic of metastatic cells. The first described suppressor of
      metastatic processes is NM23-H1, which displays NDPK (nucleoside-diphosphate
      kinase) activity. To better understand the role of nm23 genes in cell migration,
      we investigated the function of NDK-1, the sole Caenorhabditis elegans homolog of
      group I NDPKs in distal tip cell (DTC) migration. Dorsal phase of DTC migration
      is regulated by integrin mediated signaling. We find that ndk-1 loss of function
      mutants show defects in this phase. Epistasis analysis using mutants of the alpha
      integrin ina-1 and the downstream functioning motility-promoting signaling module
      (referred to as CED-10 pathway) placed NDK-1 downstream of CED-10/Rac. As DTC
      migration and engulfment of apoptotic corpses are analogous processes, both
      partially regulated by the CED-10 pathway, we investigated defects of apoptosis
      in ndk-1 mutants. Embryos and germ cells defective for NDK-1 showed an
      accumulation of apoptotic cell corpses. Furthermore, NDK-1::GFP is expressed in
      gonadal sheath cells, specialized cells for engulfment and clearence of apoptotic
      corpses in germ line, which indicates a role for NDK-1 in apoptotic corpse
      removal. In addition to the CED-10 pathway, engulfment in the worm is also
      mediated by the CED-1 pathway. abl-1/Abl and abi-1/Abi, which function in
      parallel to both CED-10/CED-1 pathways, also regulate engulfment and DTC
      migration. ndk-1(-);abi-1(-) double mutant embryos display an additive phenotype
      (e. g. enhanced number of apoptotic corpses) which suggests that ndk-1 acts in
      parallel to abi-1. Corpse number in ndk-1(-);ced-10(-) double mutants, however,
      is similar to ced-10(-) single mutants, suggesting that ndk-1 acts downstream of
      ced-10 during engulfment. In addition, NDK-1 shows a genetic interaction with DYN
      1/dynamin, a downstream component of the CED-1 pathway. In summary, we propose
      that NDK-1/NDPK might represent a converging point of CED-10 and CED-1 pathways
      in the process of cytoskeleton rearrangement. 

PMID- 24658125
TI  - Investigation of de novo unique differentially expressed genes related to
      evolution in exercise response during domestication in Thoroughbred race horses.
AB  - Previous studies of horse RNA-seq were performed by mapping sequence reads to the
      reference genome during transcriptome analysis. However in this study, we focused
      on two main ideas. First, differentially expressed genes (DEGs) were identified
      by de novo-based analysis (DBA) in RNA-seq data from six Thoroughbreds before and
      after exercise, here-after referred to as "de novo unique differentially
      expressed genes" (DUDEG). Second, by integrating both conventional DEGs and genes
      identified as being selected for during domestication of Thoroughbred and Jeju
      pony from whole genome re-sequencing (WGS) data, we give a new concept to the
      definition of DEG. We identified 1,034 and 567 DUDEGs in skeletal muscle and
      blood, respectively. DUDEGs in skeletal muscle were significantly related to
      exercise-induced stress biological process gene ontology (BP-GO) terms: 'immune
      system process'; 'response to stimulus'; and, 'death' and a KEGG pathways: 'JAK
      STAT signaling pathway'; 'MAPK signaling pathway'; 'regulation of actin
      cytoskeleton'; and, 'p53 signaling pathway'. In addition, we found TIMELESS,
      EIF4A3 and ZNF592 in blood and CHMP4C and FOXO3 in skeletal muscle, to be in
      common between DUDEGs and selected genes identified by evolutionary statistics
      such as FST and Cross Population Extended Haplotype Homozygosity (XP-EHH).
      Moreover, in Thoroughbreds, three out of five genes (CHMP4C, EIF4A3 and FOXO3)
      related to exercise response showed relatively low nucleotide diversity compared
      to the Jeju pony. DUDEGs are not only conceptually new DEGs that cannot be
      attained from reference-based analysis (RBA) but also supports previous RBA
      results related to exercise in Thoroughbred. In summary, three exercise related
      genes which were selected for during domestication in the evolutionary history of
      Thoroughbred were identified as conceptually new DEGs in this study. 

PMID- 24658126
TI  - Piwi is required in multiple cell types to control germline stem cell lineage
      development in the Drosophila ovary.
AB  - The piRNA pathway plays an important role in maintaining genome stability in the
      germ line by silencing transposable elements (TEs) from fly to mammals. As a
      highly conserved piRNA pathway component, Piwi is widely expressed in both germ
      cells and somatic cells in the Drosophila ovary and is required for piRNA
      production in both cell types. In addition to its known role in somatic cap cells
      to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has
      novel functions in somatic cells and germ cells of the Drosophila ovary to
      promote germ cell differentiation. Piwi knockdown in escort cells causes a
      reduction in escort cell (EC) number and accumulation of undifferentiated germ
      cells, some of which show active BMP signaling, indicating that Piwi is required
      to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of
      dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation
      defect, indicating that Piwi is required in ECs to repress dpp. Consistent with
      its key role in piRNA production, TE transcripts increase significantly and DNA
      damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific
      knockdown of piwi surprisingly causes depletion of germ cells before adulthood,
      suggesting that Piwi might control primordial germ cell maintenance or GSC
      establishment. Finally, Piwi inactivation in the germ line of the adult ovary
      leads to gradual GSC loss and germ cell differentiation defects, indicating the
      intrinsic role of Piwi in adult GSC maintenance and differentiation. This study
      has revealed new germline requirement of Piwi in controlling GSC maintenance and
      lineage differentiation as well as its new somatic function in promoting germ
      cell differentiation. Therefore, Piwi is required in multiple cell types to
      control GSC lineage development in the Drosophila ovary. 

PMID- 24658127
TI  - High serum levels of HDV RNA are predictors of cirrhosis and liver cancer in
      patients with chronic hepatitis delta.
AB  - Chronic infection with the hepatitis delta virus (HDV) is a risk factor for
      cirrhosis and hepatocellular carcinoma (HCC), but little is known whether the
      outcome of hepatitis is predicted by serum markers of HDV and hepatitis B virus
      (HBV) infection. The aim of the study was to investigate these correlations in
      193 patients with chronic HDV infection who had been followed up for a median of
      9.5 years (4.8-19.3). HDV-RNA was first measured by qualitative in-house nested
      RT-PCR and quantified by in-house real-time PCR. HDV RNA levels only appeared
      significantly associated to HCC (univariate analysis: OR 1.32, 95% CI 1.02-1.71;
      p = 0.037; multivariate analysis: OR 1.42, 95% CI 1.04-1.95; p = 0.03). In non
      cirrhotics at first presentation (n = 105), HDV RNA levels were associated with
      progression to cirrhosis (univariate analysis: OR = 1.57, 95% CI 1.20-2.05,
      p<0.001; multivariate analysis: OR = 1.60, 95% CI 1.20-2.12, p = 0.007) and
      development of HCC (univariate analysis: OR = 1.66, 95% CI 1.04-2.65, p = 0.033;
      multivariate analysis: OR = 1.88, 95% CI 1.11-3.19, p = 0.019). ROC analysis
      showed that approximately 600,000 HDV RNA copies/mL was the optimal cut-off value
      in our cohort of patients for discriminating the development of cirrhosis. High
      levels of HDV viremia in non-cirrhotic patients are associated with a
      considerable likelihood of progression to cirrhosis and the development of HCC.
      Once cirrhosis has developed, the role of HDV replication as a predictor of a
      negative outcome lessens. 

PMID- 24658128
TI  - Quality assurance of lower limb venous duplex scans performed by vascular
      surgeons.
AB  - AIM: Duplex scanning is the gold standard for investigating venous reflux;
      increasingly surgeons perform these scans themselves. There has been no data
      published analysing the accuracy of Duplex scans performed by vascular surgeons.
      We aimed to evaluate an objective method of comparing the results of lower limb
      Duplex scans performed by one consultant vascular surgeon with those performed by
      a vascular technologist. METHODS: We assessed 100 legs with symptomatic varicose
      veins. Each patient underwent two lower limb venous Duplex scans; one performed
      by a consultant vascular surgeon and one by a vascular technologist. Scan results
      were randomised and sent to two consultant vascular surgeons blinded to the
      identity and experience of the sonographer. They were asked to recommend
      treatment. A k score was calculated in each case to assess the level of agreement
      between the scans performed by the consultant and the technologist. RESULTS:
      Eighty-one patients were studied (53 females). The kappa score for assessor 1 was
      0.60 (95%CI:0.44-0.75) and for assessor 2 was 0.62 (95%CI:0.48-0.75). k scores
      >0.60 represent a substantial strength of agreement. CONCLUSION: Duplex scans
      performed by this surgeon were comparable to those performed by a vascular
      technologist. It is possible to quality-assure duplex performed by vascular
      surgeons without directly observing the scanning process or reviewing digitally
      recorded images. We propose standardisation of training, assessment and quality
      assurance for vascular surgeons wishing to perform ultrasound scans.

PMID- 24658129
TI  - Automated and accurate carotid bulb detection, its verification and validation in
      low quality frozen frames and motion video.
AB  - AIM: Carotid intima-media thickness (cIMT) measurements during clinical trials
      need to have a fixed reference point (also called as bulb edge points) in the
      anatomy from which the cIMT can be measured. Identification of the bulb edge
      points in carotid ultrasound images faces the challenge to be detected
      automatically due to low image quality and variations in ultrasound images,
      motion artefacts, image acquisition protocols, position of the patient, and
      orientation of the linear probe with respect to bulb and ultrasound gain controls
      during acquisition. METHODS: This paper presents a patented comprehensive
      methodology for carotid bulb localization and bulb edge detection as a reference
      point. The method consists of estimating the lumen-intima borders accurately
      using classification paradigm. Transition points are located automatically based
      on curvature characteristics. Further we verify and validate the locations of
      bulb edge points using combination of several local image processing methods such
      as (i) lumen-intima shapes, (ii) bulb slopes, (iii) bulb curvature, (iv) mean
      lumen thickness and its variations, and (v) geometric shape fitting. RESULTS: Our
      database consists of 155 ultrasound bulb images taken from various ultrasound
      machines with varying resolutions and imaging conditions. Further we run our
      automated system blindly to spot out the bulbs in a mixture database of 336
      images consisting of bulbs and no-bulbs. We are able to detect the bulbs in the
      bulb database with 100% accuracy having 92% as close as to a neurologists's bulb
      location. Our mean lumen-intima error is 0.0133 mm with precision against the
      manual tracings to be 98.92%. Our bulb detection system is fast and takes on an
      average 9 seconds per image for detection for the bulb edge points and 4 seconds
      for verification/validation of the bulb edge points.

PMID- 24658130
TI  - Quantitative influenza follow-up testing (QIFT)--a novel biomarker for the
      monitoring of disease activity at the point-of-care.
AB  - BACKGROUND: Influenza infections induce considerable disease burden in young
      children. Biomarkers for the monitoring of disease activity at the point-of-care
      (POC) are currently lacking. Recent methodologies for fluorescence-based rapid
      testing have been developed to provide improved sensitivities with the initial
      diagnosis. The present study aims to explore the utility of second-generation
      rapid testing during longitudinal follow-up of influenza patients (Rapid
      Influenza Follow-up Testing = RIFT). Signal/control fluorescent readouts
      (Quantitative Influenza Follow-up Testing = QIFT) are evaluated as a potential
      biomarker for the monitoring of disease activity at the POC. METHODS AND
      FINDINGS: RIFT (SOFIA) and QIFT were performed at the POC and compared to blinded
      RT-PCR at the National Reference Centre for Influenza. From 10/2011-4/2013, a
      total of 2048 paediatric cases were studied prospectively; 273 cases were PCR
      confirmed for influenza. During follow-up, RIFT results turned negative either
      prior to PCR (68%), or simultaneously (30%). The first negative RIFT occurred
      after a median of 8 days with a median virus load (VL) of 5.6*10?3 copies/ml and
      cycle threshold of 37, with no evidence of viral rebound. Binning analysis
      revealed that QIFT differentiated accurately between patients with low, medium
      and high viral titres. QIFT increase/decrease showed 88% agreement (sensitivity =
      52%, specificity = 95%) with VL increase/decrease, respectively. QIFT-based viral
      clearance estimates showed similar values compared to PCR-based estimates.
      Variations in viral clearance rates were lower in treated compared to untreated
      patients. The study was limited by use of non-invasive, semi-quantitative
      nasopharyngeal samples. VL measurements below the limit of detection could not be
      quantified reliably. CONCLUSIONS: During follow-up, RIFT provides a first
      surrogate measure for influenza disease activity. A "switch" from positive to
      negative values may indicate a drop in viral load below a critical threshold,
      where rebound is no longer expected. QIFT may provide a useful tool for the
      monitoring of disease burden and viral clearance at the POC.

PMID- 24658131
TI  - Either non-homologous ends joining or homologous recombination is required to
      repair double-strand breaks in the genome of macrophage-internalized
      Mycobacterium tuberculosis.
AB  - The intracellular pathogen Mycobacterium tuberculosis (Mtb) is constantly exposed
      to a multitude of hostile conditions and is confronted by a variety of
      potentially DNA-damaging assaults in vivo, primarily from host-generated
      antimicrobial toxic radicals. Exposure to reactive nitrogen species and/or
      reactive oxygen species causes different types of DNA damage, including
      oxidation, depurination, methylation and deamination, that can result in single-
      or double-strand breaks (DSBs). These breaks affect the integrity of the whole
      genome and, when left unrepaired, can lead to cell death. Here, we investigated
      the role of the DSB repair pathways, homologous recombination (HR) and non
      homologous ends joining (NHEJ), in the survival of Mtb inside macrophages. To
      this end, we constructed Mtb strains defective for HR (DeltarecA), NHEJ
      [Delta(ku,ligD)], or both DSB repair systems [Delta(ku,ligD,recA)]. Experiments
      using these strains revealed that either HR or NHEJ is sufficient for the
      survival and propagation of tubercle bacilli inside macrophages. Inhibition of
      nitric oxide or superoxide anion production with L-NIL or apocynin, respectively,
      enabled the Delta(ku,ligD,recA) mutant strain lacking both systems to survive
      intracellularly. Complementation of the Delta(ku,ligD,recA) mutant with an intact
      recA or ku-ligD rescued the ability of Mtb to propagate inside macrophages. 

PMID- 24658132
TI  - An extended DeltaCT-method facilitating normalisation with multiple reference
      genes suited for quantitative RT-PCR analyses of human hepatocyte-like cells.
AB  - Reference genes (RG) as sample internal controls for gene transcript level
      analyses by quantitative RT-PCR (RT-qPCR) must be stably expressed within the
      experimental range. A variety of in vitro cell culture settings with primary
      human hepatocytes, and Huh-7 and HepG2 cell lines, were used to determine
      candidate RG expression stability in RT-qPCR analyses. Employing GeNorm,
      BestKeeper and Normfinder algorithms, this study identifies PSMB6, MDH1 and some
      more RG as sufficiently unregulated, thus expressed at stable levels, in
      hepatocyte-like cells in vitro. Inclusion of multiple RG, quenching occasional
      regulations of single RG, greatly stabilises gene expression level calculations
      from RT-qPCR data. To further enhance validity and reproducibility of relative RT
      qPCR quantifications, the DeltaCT calculation can be extended (e-DeltaCT) by
      replacing the CT of a single RG in DeltaCT with an averaged CT-value from
      multiple RG. The use of two or three RG--here identified suited for human
      hepatocyte-like cells--for normalisation with the straightforward e-DeltaCT
      calculation, should improve reproducibility and robustness of comparative RT-qPCR
      based gene expression analyses.

PMID- 24658133
TI  - p63 transcriptionally regulates the expression of matrix metallopeptidase 13.
AB  - p63 is a transcriptional factor belonging to p53 family of genes. Beside the role
      in cancer, partially shared with p53 and the other member p73, p63 also plays
      exclusive roles in development and homeostasis of ectodermal/epidermal-related
      organs. Here we show that p63 transcriptionally controls the expression of the
      matrix metallopeptidase 13 (MMP13). p63 binds a p53-like responsive element in
      the human promoter of MMP13, thus promoting the activation of its transcription.
      The catalytic activity of MMP13 is required in high invasion capacity of
      metastatic cancer cells, however, although p63 and MMP13 expression correlates in
      cancer patients, their co-expression does not predict cancer patient survival.
      Our results demonstrate that p63 directly controls MMP13 expression. 

PMID- 24658134
TI  - Structural transformation of confined iodine in the elliptical channels of
      AlPO(4)-11 crystals under high pressure.
AB  - Iodine molecules confined in the elliptical nanochannels of AlPO4-11 crystals can
      only rotate in the plane passing through the major axis of the elliptical cross
      section due to size confinement. This leads to different dynamic behaviors of
      iodine from those confined in round channels of AlPO4-5 crystals under ambient
      conditions. In this work, we use high pressure technology to manipulate the
      nanoscaled iodine species confined in the elliptical channels of AlPO4-11
      crystals. In situ polarized Raman measurements and theoretical simulations have
      been carried out to study the topological geometry of the confined iodine species
      upon compression. It was found that the population of iodine chains could
      significantly increase at the expense of standing iodine molecules under pressure
      up to 6 GPa, due to the pressure-induced rotation of standing iodine molecules.
      Besides, the contraction of the host framework along the channel axis favors the
      formation of iodine chains and strengthens the interaction of neighbouring
      molecules in a chain, consequently leading to a frequency redshift of the
      corresponding Raman mode. The different transformation dynamics of the confined
      iodine in AlPO4-11 crystals upon compression, compared to those in round channels
      of AlPO4-5 crystals, have been discussed in terms of the unique nanochannels that
      offer the quasi two-dimensional nanoscaled confinement environment. 

PMID- 24658135
TI  - Lymphocytes as liver damage mirror of HCV related adipogenesis deregulation.
AB  - Hepatitis C virus infection leads to a wide spectrum of liver diseases ranging
      from mild chronic hepatitis to end-stage cirrhosis and hepatocellular carcinoma.
      An intriguing aspect of the HCV infection is its close connection with lipid
      metabolism playing an important role in the HCV life cycle and in its
      pathogenesis. HCV is known to be a hepatotropic virus; however, it can also
      infect peripheral blood mononuclear cells (PBMCs). The goal of the current
      investigation is to compare the adipogenesis profile of liver tissues to
      lymphocytes of HCV infected patients, in order to understand if PBMCs may reflect
      the alterations of intracellular pathways occurring during HCV-related liver
      steatosis. Using the Human Adipogenesis PCR Array, gene expression was analyzed
      in liver samples and PBMCs of chronic HCV+, HBV+ and Healthy Donors (HDs)
      patients. We observed a similar modulation of lipid metabolism in HCV+ and
      HBV+liver tissues and lymphoid, cells suggesting that PBMCs reflect the liver
      adipogenesis deregulation related to infection, even if the two viruses have a
      different impact in the regulation of the adipogenesis mechanisms. In particular,
      some genes involved in lipid metabolism and inflammation, as well as in cell
      transformation, were up-regulated, in a similar way, in both HCV models analyzed.
      Interestingly, these genes were positively correlated to virological and hepatic
      functional parameters of HCV+ patients. On the contrary, HBV+ patients displayed
      a completely different profile. PBMCs of HCV+ patients seem to be useful model to
      study how HCV-related lipid metabolism deregulation occurs in liver. The obtained
      data suggest some molecules as new possible biomarkers of HCV-related liver
      damage progression. 

PMID- 24658136
TI  - Genome-wide analysis of the chromatin composition of histone H2A and H3 variants
      in mouse embryonic stem cells.
AB  - Genome-wide distribution of the majority of H2A and H3 variants (H2A, H2AX, H2AZ,
      macroH2A, H3.1, H3.2 and H3.3) was simultaneously investigated in mouse embryonic
      stem cells by chromatin immunoprecipitation sequencing. Around the transcription
      start site, histone variant distribution differed between genes possessing
      promoters of high and low CpG density, regardless of their expression levels. In
      the intergenic regions, regulatory elements were enriched in H2A.Z and H3.3,
      whereas repeat elements were abundant in H2A and macroH2A, and H3.1,
      respectively. Analysis of H2A and H3 variant combinations composing nucleosomes
      revealed that the H2A.Z and H3.3 combinations were present at a higher frequency
      throughout the genome than the other combinations, suggesting that H2A.Z and H3.3
      associate preferentially with each other to comprise the nucleosomes
      independently of genome region. Finally, we found that chromatin was unstable
      only in regions where it was enriched in both H2A.Z and H3.3, but strongly
      quantified stable in regions in which only H3.3 was abundant. Therefore, histone
      variant composition is an important determinant of chromatin structure, which is
      associated with specific genomic functions. 

PMID- 24658137
TI  - Early warning signals of ecological transitions: methods for spatial patterns.
AB  - A number of ecosystems can exhibit abrupt shifts between alternative stable
      states. Because of their important ecological and economic consequences, recent
      research has focused on devising early warning signals for anticipating such
      abrupt ecological transitions. In particular, theoretical studies show that
      changes in spatial characteristics of the system could provide early warnings of
      approaching transitions. However, the empirical validation of these indicators
      lag behind their theoretical developments. Here, we summarize a range of
      currently available spatial early warning signals, suggest potential null models
      to interpret their trends, and apply them to three simulated spatial data sets of
      systems undergoing an abrupt transition. In addition to providing a step-by-step
      methodology for applying these signals to spatial data sets, we propose a
      statistical toolbox that may be used to help detect approaching transitions in a
      wide range of spatial data. We hope that our methodology together with the
      computer codes will stimulate the application and testing of spatial early
      warning signals on real spatial data. 

PMID- 24658139
TI  - Preclinical anatomical, molecular, and functional imaging of the lung with
      multiple modalities.
AB  - In vivo imaging is an important tool for preclinical studies of lung function and
      disease. The widespread availability of multimodal animal imaging systems and the
      rapid rate of diagnostic contrast agent development have empowered researchers to
      noninvasively study lung function and pulmonary disorders. Investigators can
      identify, track, and quantify biological processes over time. In this review, we
      highlight the fundamental principles of bioluminescence, fluorescence, planar X
      ray, X-ray computed tomography, magnetic resonance imaging, and nuclear imaging
      modalities (such as positron emission tomography and single photon emission
      computed tomography) that have been successfully employed for the study of lung
      function and pulmonary disorders in a preclinical setting. The major principles,
      benefits, and applications of each imaging modality and technology are reviewed.
      Limitations and the future prospective of multimodal imaging in pulmonary
      physiology are also discussed. In vivo imaging bridges molecular biological
      studies, drug design and discovery, and the imaging field with modern medical
      practice, and, as such, will continue to be a mainstay in biomedical research. 

PMID- 24658138
TI  - Human airway epithelia express catalytically active NEU3 sialidase.
AB  - Sialic acids on glycoconjugates play a pivotal role in many biological processes.
      In the airways, sialylated glycoproteins and glycolipids are strategically
      positioned on the plasma membranes of epithelia to regulate receptor-ligand, cell
      cell, and host-pathogen interactions at the molecular level. We now demonstrate,
      for the first time, sialidase activity for ganglioside substrates in human airway
      epithelia. Of the four known mammalian sialidases, NEU3 has a substrate
      preference for gangliosides and is expressed at mRNA and protein levels at
      comparable abundance in epithelia derived from human trachea, bronchi, small
      airways, and alveoli. In small airway and alveolar epithelia, NEU3 protein was
      immunolocalized to the plasma membrane, cytosolic, and nuclear subcellular
      fractions. Small interfering RNA-induced silencing of NEU3 expression diminished
      sialidase activity for a ganglioside substrate by >70%. NEU3 immunostaining of
      intact human lung tissue could be localized to the superficial epithelia,
      including the ciliated brush border, as well as to nuclei. However, NEU3 was
      reduced in subepithelial tissues. These results indicate that human airway
      epithelia express catalytically active NEU3 sialidase. 

PMID- 24658140
TI  - The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein
      interactions in human cells.
AB  - Cell signaling, one of key processes in both normal cellular function and
      disease, is coordinated by numerous interactions between membrane proteins that
      change in response to stimuli. We present a split ubiquitin-based method for
      detection of integral membrane protein-protein interactions (PPIs) in human
      cells, termed mammalian-membrane two-hybrid assay (MaMTH). We show that this
      technology detects stimulus (hormone or agonist)-dependent and phosphorylation
      dependent PPIs. MaMTH can detect changes in PPIs conferred by mutations such as
      those in oncogenic ErbB receptor variants or by treatment with drugs such as the
      tyrosine kinase inhibitor erlotinib. Using MaMTH as a screening assay, we
      identified CRKII as an interactor of oncogenic EGFR(L858R) and showed that CRKII
      promotes persistent activation of aberrant signaling in non-small cell lung
      cancer cells. MaMTH is a powerful tool for investigating the dynamic interactomes
      of human integral membrane proteins. 

PMID- 24658141
TI  - Function-based identification of mammalian enhancers using site-specific
      integration.
AB  - The accurate and comprehensive identification of functional regulatory sequences
      in mammalian genomes remains a major challenge. Here we describe site-specific
      integration fluorescence-activated cell sorting followed by sequencing (SIF-seq),
      an unbiased, medium-throughput functional assay for the discovery of distant
      acting enhancers. Targeted single-copy genomic integration into pluripotent
      cells, reporter assays and flow cytometry are coupled with high-throughput DNA
      sequencing to enable parallel screening of large numbers of DNA sequences. By
      functionally interrogating >500 kilobases (kb) of mouse and human sequence in
      mouse embryonic stem cells for enhancer activity we identified enhancers at
      pluripotency loci including NANOG. In in vitro-differentiated cardiomyocytes and
      neural progenitor cells, we identified cardiac enhancers and neuronal enhancers,
      respectively. SIF-seq is a powerful and flexible method for de novo functional
      identification of mammalian enhancers in a potentially wide variety of cell
      types. 

PMID- 24658143
TI  - Influence of environmental factors on the germination of Urena lobata L. and its
      response to herbicides.
AB  - Urena lobata is becoming a noxious and invasive weed in rangelands, pastures, and
      undisturbed areas in the Philippines. This study determined the effects of seed
      scarification, light, salt and water stress, amount of rice residue, and seed
      burial depth on seed germination and emergence of U. lobata; and evaluated the
      weed's response to post-emergence herbicides. Germination was stimulated by both
      mechanical and chemical seed scarifications. The combination of the two
      scarification methods provided maximum (99%) seed germination. Germination was
      slightly stimulated when seeds were placed in light (65%) compared with when
      seeds were kept in the dark (46%). Sodium chloride concentrations ranging from 0
      to 200 mM and osmotic potential ranging from 0 to -1.6 MPa affected the
      germination of U. lobata seeds significantly. The osmotic potential required for
      50% inhibition of the maximum germination was -0.1 MPa; however, some seeds
      germinated at -0.8 MPa, but none germinated at -1.6 MPa. Seedling emergence and
      biomass increased with increase in rice residue amount up to 4 t ha(-1), but
      declined beyond this amount. Soil surface placement of weed seeds resulted in the
      highest seedling emergence (84%), which declined with increase in burial depth.
      The burial depth required for 50% inhibition of maximum emergence was 2 cm;
      emergence was greatly reduced (93%) at burial depth of 4 cm or more. Weed
      seedling biomass also decreased with increase in burial depth. Bispyribac-sodium,
      a commonly used herbicide in rice, sprayed at the 4-leaf stage of the weed,
      provided 100% control, which did not differ much with 2,4-D (98%), glyphosate
      (97%), and thiobencarb + 2,4-D (98%). These herbicides reduced shoot and root
      biomass by 99-100%.

PMID- 24658142
TI  - FIREWACh: high-throughput functional detection of transcriptional regulatory
      modules in mammalian cells.
AB  - Promoters and enhancers establish precise gene transcription patterns. The
      development of functional approaches for their identification in mammalian cells
      has been complicated by the size of these genomes. Here we report a high
      throughput functional assay for directly identifying active promoter and enhancer
      elements called FIREWACh (Functional Identification of Regulatory Elements Within
      Accessible Chromatin), which we used to simultaneously assess over 80,000 DNA
      fragments derived from nucleosome-free regions within the chromatin of embryonic
      stem cells (ESCs) and identify 6,364 active regulatory elements. Many of these
      represent newly discovered ESC-specific enhancers, showing enriched binding-site
      motifs for ESC-specific transcription factors including SOX2, POU5F1 (OCT4) and
      KLF4. The application of FIREWACh to additional cultured cell types will
      facilitate functional annotation of the genome and expand our view of
      transcriptional network dynamics. 

PMID- 24658144
TI  - Shear wave speed and dispersion measurements using crawling wave chirps.
AB  - This article demonstrates the measurement of shear wave speed and shear speed
      dispersion of biomaterials using a chirp signal that launches waves over a range
      of frequencies. A biomaterial is vibrated by two vibration sources that generate
      shear waves inside the medium, which is scanned by an ultrasound imaging system.
      Doppler processing of the acquired signal produces an image of the square of
      vibration amplitude that shows repetitive constructive and destructive
      interference patterns called "crawling waves." With a chirp vibration signal,
      successive Doppler frames are generated from different source frequencies.
      Collected frames generate a distinctive pattern which is used to calculate the
      shear speed and shear speed dispersion. A special reciprocal chirp is designed
      such that the equi-phase lines of a motion slice image are straight lines.
      Detailed analysis is provided to generate a closed-form solution for calculating
      the shear wave speed and the dispersion. Also several phantoms and an ex vivo
      human liver sample are scanned and the estimation results are presented. 

PMID- 24658145
TI  - Palladium-catalyzed R2(O)P directed C(sp2)-H acetoxylation.
AB  - A novel and efficient Pd-catalyzed C-H acetoxylation is described. The approach
      uses R2(O)P as a directing group to synthesize various substituted 2'
      phosphorylbiphenyl-2-OAc compounds. Notably, the reaction exhibits smooth
      operation under mild conditions and shows good functional group tolerance.
      Products are obtained with high selectivity and yields. 

PMID- 24658146
TI  - Subcellular fractionation and localization studies reveal a direct interaction of
      the fragile X mental retardation protein (FMRP) with nucleolin.
AB  - Fragile X mental Retardation Protein (FMRP) is a well-known regulator of local
      translation of its mRNA targets in neurons. However, despite its ubiquitous
      expression, the role of FMRP remains ill-defined in other cell types. In this
      study we investigated the subcellular distribution of FMRP and its protein
      complexes in HeLa cells using confocal imaging as well as detergent-free
      fractionation and size exclusion protocols. We found FMRP localized exclusively
      to solid compartments, including cytosolic heavy and light membranes,
      mitochondria, nuclear membrane and nucleoli. Interestingly, FMRP was associated
      with nucleolin in both a high molecular weight ribosomal and translation
      associated complex (>=6 MDa) in the cytosol, and a low molecular weight complex
      (~200 kDa) in the nucleoli. Consistently, we identified two functional nucleolar
      localization signals (NoLSs) in FMRP that are responsible for a strong nucleolar
      colocalization of the C-terminus of FMRP with nucleolin, and a direct interaction
      of the N-terminus of FMRP with the arginine-glycine-glycine (RGG) domain of
      nucleolin. Taken together, we propose a novel mechanism by which a transient
      nucleolar localization of FMRP underlies a strong nucleocytoplasmic
      translocation, most likely in a complex with nucleolin and possibly ribosomes, in
      order to regulate translation of its target mRNAs. 

PMID- 24658147
TI  - One-step growth of triangular silver nanoplates with predictable sizes on a large
      scale.
AB  - A one-step growth of triangular silver nanoplates on a large scale is developed
      by a coordination-based kinetically controlled seeded growth method, with their
      edge length precisely tuned from 150 nm to 1.5 MUm, and surface plasmon resonance
      extends to full near-infrared. 

PMID- 24658148
TI  - Prospective randomized comparison of knee stability and joint degeneration for
      double- and single-bundle ACL reconstruction.
AB  - PURPOSE: This study aims to determine the outcome of double-bundle anterior
      cruciate ligament (ACL) reconstruction using an allograft in comparison with ACL
      reconstruction using a double-bundle autograft or a single-bundle allograft.
      METHODS: A total of 424 patients who accepted primary ACL reconstructions were
      divided randomly into three groups: double-bundle technique with autograft (DB-AU
      group, n = 154), double-bundle technique with allograft (DB-AL group, n = 128),
      and single-bundle technique with allograft (SB group, n = 142). The KT-1000
      arthrometer and pivot-shift tests were performed at 3, 12, and 36 months after
      surgery, and clinical outcome measurements include the Lysholm score and the IKDC
      rating scales. Radiological assessments evaluated arthritic changes and tunnel
      expansion at 36 months postoperatively. RESULTS: The KT-1000 test scores in the
      DB-AU and DB-AL groups were significantly better than those in the SB group at 12
      and 36 months postoperatively (P < 0.05). The pivot-shift tests scores in the DB
      AU and DB-AL groups were significantly better than those in the SB group at the
      3, 12, and 36 month follow-ups (P < 0.05). Based on the IKDC score and Lysholm
      score, there were no significant difference between the three groups during
      follow-up (P > 0.05). At 36 months postoperatively, 42.3 % of patients in the SB
      group showed a progression in arthritic changes, which was greater than in the DB
      AU (29.2 %) and DB-AL (27.3 %) groups (P < 0.05). At 36 months, the rates of
      tunnel expansion in the DB-AU group and the DB-AL group were lower than in the SB
      group (P < 0.05). CONCLUSIONS: Double-bundle ACL reconstruction can be used to
      achieve better anterior and rotational stability and has a lower rate of
      arthritic progression and tunnel expansion than the single-bundle procedure.
      LEVEL OF EVIDENCE: I.

PMID- 24658149
TI  - Minimally invasive medial patellofemoral ligament reconstruction with fascia lata
      allograft: surgical technique.
AB  - The present paper describes a new minimally invasive anatomic medial
      patellofemoral ligament reconstruction, using a fascia lata allograft as graft
      source and arthroscopy to obtain balanced fixation throughout the range of
      motion. 

PMID- 24658150
TI  - Increased medial foot loading during drop jump in subjects with patellofemoral
      pain.
AB  - PURPOSE: To compare medial-to-lateral plantar forces during drop jump and single
      leg squat in individuals with and without patellofemoral pain. METHODS: This
      cross-sectional study compared 23 young adults with patellofemoral pain to 20 age
      and sex-matched controls without knee pain. The plantar pressure distribution
      was collected during drop jump and single leg squat using pressure-sensitive
      Pedar insoles, inserted into a standard flat shoe. The primary outcome was the
      medial-to-lateral force, quantified as the peak force under the medial forefoot
      as the percentage of force under the total forefoot during drop jump. Secondary
      outcomes included peak medial-to-lateral force during single leg squat and mean
      forces during drop jump and single leg squat. RESULTS: The primary outcome showed
      that individuals with patellofemoral pain had a 22% higher medial-to-lateral peak
      force during drop jump, (p=0.03). Secondary outcomes showed 32% higher medial-to
      lateral peak force during single leg squat (p=0.01) and 19-23% higher medial-to
      lateral mean force during drop jump and single leg squat (p=0.02-0.04).
      CONCLUSION: These findings indicate that individuals with patellofemoral pain
      display a more medially oriented loading pattern of the forefoot compared to
      individuals without knee pain. This loading pattern may be associated with the
      distribution of forces acting on the patellofemoral joint and suggest treatment
      of PFP should consider interventions that target normalisation of foot loading.
      LEVEL OF EVIDENCE: III.

PMID- 24658151
TI  - Multifactorial comparative proteomic study of cytochrome P450 2E1 function in
      chronic alcohol administration.
AB  - With the use of iTRAQ technique, a multifactorial comparative proteomic study can
      be performed. In this study, to obtain an overview of ethanol, CYP2E1 and gender
      effects on liver injury and gain more insight into the underlying molecular
      mechanism, mouse liver proteomes were quantitatively analyzed using iTRAQ under
      eight conditions including mice of different genders, wild type versus CYP2E1
      knockout, and normal versus alcohol diet. A series of statistical and
      bioinformatic analyses were explored to simplify and clarify multifactorial
      comparative proteomic data. First, with the Principle Component analysis, six
      proteins, CYP2E1, FAM25, CA3, BHMT, HIBADH and ECHS1, involved in oxidation
      reduction, energy and lipid metabolism and amino acid metabolism, were identified
      as the most differentially expressed gene products across all of the experimental
      conditions of our chronic alcoholism model. Second, hierarchical clustering
      analysis showed CYP2E1 knockout played a primary role in the overall differential
      protein expression compared with ethanol and gender factors. Furthermore, pair
      wise multiple comparisons have revealed that the only significant expression
      difference lied in wild-type and CYP2E1 knockout mice both treated with ethanol.
      Third, K-mean clustering analysis indicated that the CYP2E1 knockout had the
      reverse effect on ethanol induced oxidative stress and lipid oxidation. More
      importantly, IPA analysis of proteomic data inferred that the gene expressions of
      two upstream regulators, NRF2 and PPARalpha, regulated by chronic alcohol feeding
      and CYP2E1 knockout, are involved in ethanol induced oxidative stress and lipid
      oxidation. The present study provides an effectively comprehensive data analysis
      strategy to compare multiple biological factors, contributing to biochemical
      effects of alcohol on the liver. The mass spectrometry proteomics data have been
      deposited to the ProteomeXchange with data set identifier of PXD000635. 

PMID- 24658152
TI  - Pedicle screws adjacent to the great vessels or viscera: a study of 2132 pedicle
      screws in pediatric spine deformity.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To determine the incidence of
      pedicle screws close to vital structures and to identify patient or curve
      characteristics that increase the risk of screw misplacement. SUMMARY AND
      BACKGROUND: Most pedicle screw misplacements are asymptomatic, thus they are
      frequently undetected. This study identifies the rate of screw placement in
      proximity to vital structures using postoperative computed tomography scans.
      METHODS: A total of 2132 screws in 101 patients, who underwent posterior spinal
      fusion for spinal deformity, were reviewed. Screws adjacent to great vessels and
      viscera were identified and evaluated. Patients with screws at risk (group B)
      were compared with patients without screws at risk (group A). Patient and curve
      characteristics were analyzed to determine whether a correlation with screw
      misplacement exists. RESULTS: A total of 40 at risk screws (~2%) were identified
      in 25 patients (~25%). These 40 screws were in proximity to the aorta (31), left
      subclavian artery (1), esophagus (3), trachea (3), pleura (1), and diaphragm (1).
      Of the 31 screws close to the aorta, 10 screws in 6 patients were impinging or
      distorting the aortic wall. One hundred percent of misplaced screws were in the
      thoracic spine, 50% were misplaced laterally, 50% were 35 mm long, 57.5% were in
      pedicles with normal morphology, and 75% were in curves between 40 and 70
      degrees. Median screw misplacement rate was 10% in group A and 13% in group B.
      Adjusted for age and preoperative Cobb angle, patients with a higher misplacement
      rate were more likely to have screws adjacent to vital organs [adjusted odds
      ratio: 1.06 (95% confidence interval, 1.01-1.13), P=0.033]. CONCLUSIONS: Although
      only a small number of screws were at risk, they occurred in a large percentage
      of patients (25%). A single at-risk screw causes a significant complication for
      the patient. Postoperative imaging beyond routine x-rays may be needed to detect
      at-risk screws in asymptomatic patients.

PMID- 24658155
TI  - Minimal residual disease in breast cancer: in blood veritas.
AB  - A blood-based molecular test might direct recommendations for systemic therapies
      in patients with early-stage breast cancer undergoing surgery with curative
      intent. A new study suggests that droplet digital PCR (ddPCR) can be used to
      detect cancer-specific DNA alterations in plasma with sensitivity suitable for
      monitoring minimal residual disease.

PMID- 24658154
TI  - Recognition and killing of autologous, primary glioblastoma tumor cells by human
      cytomegalovirus pp65-specific cytotoxic T cells.
AB  - PURPOSE: Despite aggressive conventional therapy, glioblastoma (GBM) remains
      uniformly lethal. Immunotherapy, in which the immune system is harnessed to
      specifically attack malignant cells, offers a treatment option with less
      toxicity. The expression of cytomegalovirus (CMV) antigens in GBM presents a
      unique opportunity to target these viral proteins for tumor immunotherapy.
      Although the presence of CMV within malignant gliomas has been confirmed by
      several laboratories, its relevance as an immunologic target in GBM has yet to be
      established. The objective of this study was to explore whether T cells
      stimulated by CMV pp65 RNA-transfected dendritic cells (DC) target and eliminate
      autologous GBM tumor cells in an antigen-specific manner. EXPERIMENTAL DESIGN: T
      cells from patients with GBM were stimulated with autologous DCs pulsed with CMV
      pp65 RNA, and the function of the effector CMV pp65-specific T cells was
      measured. RESULTS: In this study, we demonstrate the ability to elicit CMV pp65
      specific immune responses in vitro using RNA-pulsed autologous DCs generated from
      patients with newly diagnosed GBM. Importantly, CMV pp65-specific T cells lyse
      autologous, primary GBM tumor cells in an antigen-specific manner. Moreover, T
      cells expanded in vitro using DCs pulsed with total tumor RNA demonstrated a 10-
      to 20-fold expansion of CMV pp65-specific T cells as assessed by tetramer
      analysis and recognition and killing of CMV pp65-expressing target cells.
      CONCLUSION: These data collectively demonstrate that CMV-specific T cells can
      effectively target glioblastoma tumor cells for immunologic killing and support
      the rationale for the development of CMV-directed immunotherapy in patients with
      GBM.

PMID- 24658156
TI  - A signature predicting poor prognosis in gastric and ovarian cancer represents a
      coordinated macrophage and stromal response.
AB  - PURPOSE: Gene-expression profiling has revolutionized the way we think about
      cancer and confers the ability to observe the synchronous expression of thousands
      of genes. The use of putative genome-level expression profiles has allowed
      biologists to observe the complex interactions of genes that constitute
      recognized biologic pathways. We used gastric and ovarian datasets to identify
      gene-expression signatures and determine any functional significance.
      EXPERIMENTAL DESIGN: Microarray data of 94-tumor and 45-benign samples derived
      from patients with gastric cancer were interrogated using Hierarchical Ordered
      Partitioning and Collapsing Hybrid analysis identifying clusters of coexpressed
      genes. Clusters were further characterized with respect to biologic significance,
      gene ontology, and ability to discriminate between normal and tumor tissue. Tumor
      tissues were separated into epithelial and stromal compartments and
      immunohistochemical analysis performed to further elucidate specific cell
      lineages expressing genes contained in the signature. RESULTS: We identified a
      "stromal-response" expression signature, highly enriched for inflammatory,
      extracellular matrix, cytokine, and growth factor proteins. The majority of genes
      in the signature are expressed in the tumor-associated stroma but were absent in
      associated premalignant conditions. In gastric cancer, this module almost
      perfectly differentiates tumor from nonmalignant gastric tissue and hence can be
      regarded as a highly tumor-specific gene-expression signature. CONCLUSIONS: We
      show that these genes are consistently coexpressed across a range of independent
      gastric datasets as well as other cancer types suggesting a conserved functional
      role in cancer. In addition, we show that this signature can be a surrogate
      marker for M2 macrophage activity and has significant prognostic implications in
      gastric and ovarian high-grade serous cancer.

PMID- 24658157
TI  - Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR
      200c-Sox2-negative feedback loop mechanism.
AB  - PURPOSE: To elucidate a novel mechanism of miR-200c in the regulation of
      stemness, growth, and metastasis in colorectal carcinoma (CRC). EXPERIMENTAL
      DESIGN: Quantitative reverse transcription PCR was used to quantify miR-200c
      expression in CRC cell lines and tissues. A luciferase assay was adopted for the
      target evaluation. The functional effects of miR-200c in CRC cells were assessed
      by its forced or inhibited expression using lentiviruses. RESULTS: MiR-200c was
      statistically lower in CRC clinical specimens and highly metastatic CRC cell
      lines compared with their counterparts. Sox2 was validated as a target for miR
      200c. The knockdown of miR-200c significantly enhanced proliferation, migration,
      and invasion in CRC cell lines, whereas the upregulation of miR-200c exhibited an
      inverse effect. Moreover, rescue of Sox2 expression could abolish the effect of
      the upregulation of miR-200c. In addition, the reduction of miR-200c increased
      the expression of CRC stem cell markers and the sphere-forming capacity of CRC
      cell lines. Further study has shown that miR-200c and Sox2 reciprocally control
      their expression through a feedback loop. MiR-200c suppresses the expression of
      Sox2 to block the activity of the phosphoinositide 3-kinase (PI3K)-AKT pathway.
      CONCLUSION: Our findings indicate that miR-200c regulates Sox2 expression through
      a feedback loop and is associated with CRC stemness, growth, and metastasis.

PMID- 24658158
TI  - MET is a potential target across all papillary renal cell carcinomas: result from
      a large molecular study of pRCC with CGH array and matching gene expression
      array.
AB  - PURPOSE: Papillary renal cell carcinomas (pRCC) are the most common nonclear cell
      RCC subtype. Germline mutations of the MET oncogene at 7q31 have been detected in
      patients with hereditary type I pRCC and in 13% of sporadic type I pRCC. Recent
      report of MET inhibition strengthened the role of c-Met inhibition across pRCC.
      EXPERIMENTAL DESIGN: We collected 220 frozen samples of sporadic pRCC through the
      French RCC Network and quality controlled for percentage of malignant cells >70%.
      Gene expression was assessed on 98 pRCC using human whole-genome Agilent 8 * 60K
      arrays. Copy number alterations were analyzed using Agilent Human 2 * 400K and 4*
      180K array for type II pRCC and comparative genomic microarray analysis method
      for type I pRCC. MET gene sequencing was performed on type I pRCC. RESULTS: MET
      expression level was high across all pRCC. We identified copy number alterations
      (gain) in 46% of type II pRCC and in 81% of type I pRCC. Correlation between DNA
      copy number alterations and mRNA expression level was highly significant. Eleven
      somatic mutations of MET gene were identified amongst 51 type I pRCC (21.6%),
      including 4 new mutations. We validated LRRK2 cokinase as highly correlated to
      MET expression. CONCLUSION: The present report expands the role of MET activation
      as a potential target across all pRCC subtypes. These data support investigating
      MET inhibitors in pRCC in correlation with MET activation status.

PMID- 24658159
TI  - Application of a 3D printed customized implant for canine cruciate ligament
      treatment by tibial tuberosity advancement.
AB  - Fabrication of customized implants based on patient bone defect characteristics
      is required for successful clinical application of bone tissue engineering.
      Recently a new surgical procedure, tibial tuberosity advancement (TTA), has been
      used to treat cranial cruciate ligament (CrCL) deficient stifle joints in dogs,
      which involves an osteotomy and the use of substitutes to restore the bone.
      However, limitations in the use of non-biodegradable implants have been reported.
      To overcome these limitations, this study presents the development of a
      bioceramic customized cage to treat a large domestic dog assigned for TTA
      treatment. A cage was designed using a suitable topology optimization methodology
      in order to maximize its permeability whilst maintaining the structural
      integrity, and was manufactured using low temperature 3D printing and implanted
      in a dog. The cage material and structure was adequately characterized prior to
      implantation and the in vivo response was carefully monitored regarding the
      biological response and patient limb function. The manufacturing process resulted
      in a cage composed of brushite, monetite and tricalcium phosphate, and a highly
      permeable porous morphology. An overall porosity of 59.2% was achieved by the
      combination of a microporosity of approximately 40% and a designed interconnected
      macropore network with pore sizes of 845 MUm. The mechanical properties were in
      the range of the trabecular bone although limitations in the cage's reliability
      and capacity to absorb energy were identified. The dog's limb function was
      completely restored without patient lameness or any adverse complications and
      also the local biocompatibility and osteoconductivity were improved. Based on
      these observations it was possible to conclude that the successful design,
      fabrication and application of a customized cage for a dog CrCL treatment using a
      modified TTA technique is a promising method for the future fabrication of
      patient-specific bone implants, although clinical trials are required.

PMID- 24658160
TI  - A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of
      artificial platelet nanoconstructs without interfering with VWF-adhesion of
      natural platelets.
AB  - There is substantial clinical interest in synthetic platelet analogs for
      potential application in transfusion medicine. To this end, our research is
      focused on self-assembled peptide-lipid nanoconstructs that can undergo injury
      site-selective adhesion and subsequently promote site-directed active platelet
      aggregation, thus mimicking platelet's primary hemostatic actions. For injury
      site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF
      binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet
      GPIbalpha binds to VWF's A1 domain. Therefore, we hypothesized that the VBP
      decorated nanoconstructs will adhere to VWF without mutual competition with
      natural platelets. We further hypothesized that the adherent VBP-decorated
      constructs can enhance platelet aggregation when co-decorated with a fibrinogen
      mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to
      selectively block VWF's A1 domain and, using fluorescence microscopy, studied the
      binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to
      ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP
      and FMP and incubated them with human platelets to study construct-mediated
      enhancement of platelet aggregation. Decoration with VBP resulted in substantial
      construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by
      glycocalicin. In comparison, such A1-blocking resulted in significant reduction
      of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and
      natural platelets could adhere to VWF concomitantly. Furthermore, the constructs
      co-decorated with VBP and FMP enhanced active platelet aggregation. The results
      indicate significant promise in utilizing the FVIII-derived VBP in developing
      synthetic platelet analogs that do not interfere with VWF-binding of natural
      platelets but allow site-directed enhancement of platelet aggregation when
      combined with FMP. 

PMID- 24658161
TI  - SENP5 mediates breast cancer invasion via a TGFbetaRI SUMOylation cascade.
AB  - Identifying novel mechanisms, which are at the core of breast cancer biology, is
      of critical importance. Such mechanisms may explain response to treatment, reveal
      novel targets or drive detection assays. To uncover such novel mechanisms, we
      used survival analysis on gene expression datasets encompassing 1363 patients. By
      iterating over the compendia of genes, we screened for their significance as
      prognosis biomarkers and identified SUMO-specific protease 5 (SENP5) to
      significantly stratify patients into two survival groups across five unrelated
      tested datasets. According to these findings, low expression of SENP5 is
      associated with good prognosis among breast cancer patients. Following these
      findings, we analyzed SENP5 silencing and show it is followed by inhibition of
      anchorage-independence growth, proliferation, migration and invasion in breast
      cancer cell lines. We further show that these changes are conducted via
      regulation of TGFbetaRI levels. These data relate to recent reports about the
      SUMOylation of TGFbetaRI. Following TGFbetaRI changes in expression, we show that
      one of its target genes, MMP9, which plays a key role in degrading the
      extracellular matrix and contributes to TGFbeta-induced invasion, is dramatically
      down regulated upon SENP5 silencing. This is the first report represents SENP5
      TGFbeta-MMP9 cascade and its mechanistic involvement in breast cancer. 

PMID- 24658163
TI  - Artificial photosynthesis--functional devices for light driven water splitting
      with photoactive anodes based on molecular catalysts.
AB  - Photoactive anodes consisting of Ru(bpy)3 type photosensitizer 1 and molecular
      catalysts 2 and 3 on nanostructured TiO2 have been assembled in functional
      devices for successful light driven water splitting. From their performance
      measurements we found that the photoanode TiO2(1 + 3) in which the molecular
      ruthenium catalyst and the phosphonate anchoring group are linked by a flexible 
      CH2CH2CH2- chain showed a significantly higher photocurrent density than the
      photoanode TiO2(1 + 2) with only -CH2- linkage. The possible reasons for the
      different water splitting performance of otherwise identical devices are
      discussed.

PMID- 24658162
TI  - Impaired mitochondrial dynamics and bioenergetics in diabetic skeletal muscle.
AB  - In most cells, mitochondria are highly dynamic organelles that constantly fuse,
      divide and move. These processes allow mitochondria to redistribute in a cell and
      exchange contents among the mitochondrial population, and subsequently repair
      damaged mitochondria. However, most studies on mitochondrial dynamics have been
      performed on cultured cell lines and neurons, and little is known about whether
      mitochondria are dynamic organelles in vivo, especially in the highly specialized
      and differentiated adult skeletal muscle cells. Using mitochondrial matrix
      targeted photoactivatable green fluorescent protein (mtPAGFP) and electroporation
      methods combined with confocal microscopy, we found that mitochondria are dynamic
      in skeletal muscle in vivo, which enables mitochondria exchange contents within
      the whole mitochondrial population through nanotunneling-mediated mitochondrial
      fusion. Mitochondrial network promotes rapid transfer of mtPAGFP within the cell.
      More importantly, the dynamic behavior was impaired in high-fat diet (HFD)
      induced obese mice, accompanying with disturbed mitochondrial respiratory
      function and decreased ATP content in skeletal muscle. We further found that
      proteins controlling mitochondrial fusion MFN1 and MFN2 but not Opa1 were
      decreased and proteins governing mitochondrial fission Fis1 and Drp1 were
      increased in skeletal muscle of HFD-induced mice when compared to normal diet-fed
      mice. Altogether, we conclude that mitochondria are dynamic organelles in vivo in
      skeletal muscle, and it is essential in maintaining mitochondrial respiration and
      bioenergetics. 

PMID- 24658164
TI  - Obesity and vitamin D deficiency: trends to promote a more proatherogenic
      cardiometabolic risk profile.
AB  - Vitamin D deficiency is associated with cardiometabolic risk factors (eg,
      hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and
      dyslipidemia). We studied 50 obese patients (body mass index [BMI]: 43.5 +/- 9.2
      kg/m(2)) and 36 normal weight participants (BMI: 22.6 +/- 1.9 kg/m(2)). The
      prevalence of vitamin D deficiency (25-hydroxyvitamin D, 25(OH)D < 50 nmol/L) was
      88% among obese patients and 31% among nonobese individuals; 25(OH)D levels were
      lower in the obese group (27.3 +/- 13.7 vs 64.6 +/- 21.3 nmol/L; P < .001). There
      was a negative correlation between vitamin D level and anthropometric indicators
      of obesity: BMI (r = -0.64; P < .001), waist circumference (r = -0.59; P < .001),
      and body fat percentage (r = -0.64; P < .001) as well as with fasting plasma
      insulin (r = -0.35; P < .001) and homeostasis model assessment of insulin
      resistance (r = -0.35; P < .001). In conclusion, we observed a higher prevalence
      of vitamin D deficiency among obese participants and this was associated with a
      proatherogenic cardiometabolic risk profile. 

PMID- 24658165
TI  - Olfactory dysfunction in diabetes: a further step in exploring central
      manifestations of neuropathy?

PMID- 24658166
TI  - Systemic vascular inflammation in abdominal aortic aneurysm patients: a contrast
      enhanced PET/CT study.
AB  - AIM: The aim of this paper was to investigate the presence of systemic vascular
      inflammation and its relationship with risk factors and biomarkers of systemic
      inflammation related to atherosclerosis in asymptomatic abdominal aortic aneurysm
      (AAA) patients. METHODS: Thirty AAA patients and 30 age-matched controls
      underwent contrast-enhanced 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET/CT. C
      reactive protein, erythrocyte sedimentation rate, white blood cell count and
      differential, serum fibrinogen, D-dimer and full lipid panel were also evaluated.
      Region of interest analyses were performed to obtain target-to-background (TBR)
      metabolism of aorta, subclavian, carotid, iliac arteries and AAA. CT-based
      arterial calcium load (CL) was evaluated. Arterial Metabolism and CL intergroup
      differences were tested (unpaired t-test). Linear regression analysis was
      performed only between blood biomarkers on one side and both TBR and ACL of the
      arterial districts that resulted significantly different between patients and
      controls on the other. In all the analyses P values <0.05 were considered
      significant. RESULT: FDG-uptake was higher with respect to controls in aorta,
      carotid and iliac arteries (P<0.01, P<0.007, P<0.04 respectively). AAA and aorta
      metabolism showed an inverse correlation with HDL-chol (P<0.02 and P<0.01,
      respectively) while only aorta showed a direct correlation with lymphocytes'
      count (P<0.02). Carotid metabolism was directly correlated with monocytes' count
      and C-reactive protein concentration (P<0.02 and P<0.004, respectively).
      CONCLUSION: The present findings support the relevance of systemic vascular
      inflammation in all phases of atherosclerosis-related disorders. Moreover they
      confirm the concept that acute ischemic syndromes might represent the local
      result of a systemic inflammation rather than the focal involvement of a single
      arterial lesion.

PMID- 24658167
TI  - Estimation of coronary flow reserve by sestamibi imaging in patients with mild
      hypertension and normal coronary arteries.
AB  - AIM: Patients with hypertension may exhibit abnormal vasodilator capacity during
      pharmacological vasodilatation. We assessed coronary flow reserve (CFR) by
      sestamibi imaging in hypertensive patients with normal coronary vessels. METHODS:
      Twenty-five patients with untreated mild essential hypertension and normal
      coronary vessels and 10 control subjects underwent dipyridamole-rest Tc-99m
      sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first
      transit counts in pulmonary artery and myocardial counts from tomograhic images.
      CFR was expressed as the ratio of stress to rest MBF. Coronary vascular
      resistances (CVR) were computed as the ratio between mean arterial pressure and
      MBF. RESULTS: Estimated MBF at rest was not different in patients and controls
      (1.11 +/- 0.59 vs. 1.14 +/- 0.28 counts/pixel/s; P=0.87). Conversely, stress MBF
      was lower in patients than in controls (1.55 +/- 0.47 vs. 2.68 +/- 0.53
      counts/pixel/s; P<0.001). Thus, CFR was reduced in patients compared to controls
      (1.61 +/- 0.58 vs. 2.43 +/- 0.62; P<0.001). Rest and stress CVR values were
      higher in patients (P<0.001), while stress-induced changes in CVR were not
      different (P=0.08) between patients (-51%) and controls (-62%). In the overall
      study population, a significant relation between CFR and stress-induced changes
      in CVR was observed (r=-0.86; P<0.001). CONCLUSION: Sestamibi imaging may detect
      impaired coronary vascular function in response to dipyridamole in patients with
      untreated mild essential hypertension and normal coronary arteries. A mild
      increase in arterial blood pressure does not affect baseline MBF, but impairs
      coronary reserve due to the amplified resting coronary resistances.

PMID- 24658168
TI  - Subnanometre resolution in three-dimensional magnetic resonance imaging of
      individual dark spins.
AB  - Magnetic resonance imaging (MRI) has revolutionized biomedical science by
      providing non-invasive, three-dimensional biological imaging. However, spatial
      resolution in conventional MRI systems is limited to tens of micrometres, which
      is insufficient for imaging on molecular scales. Here, we demonstrate an MRI
      technique that provides subnanometre spatial resolution in three dimensions, with
      single electron-spin sensitivity. Our imaging method works under ambient
      conditions and can measure ubiquitous 'dark' spins, which constitute nearly all
      spin targets of interest. In this technique, the magnetic quantum-projection
      noise of dark spins is measured using a single nitrogen-vacancy (NV) magnetometer
      located near the surface of a diamond chip. The distribution of spins surrounding
      the NV magnetometer is imaged with a scanning magnetic-field gradient. To
      evaluate the performance of the NV-MRI technique, we image the three-dimensional
      landscape of electronic spins at the diamond surface and achieve an unprecedented
      combination of resolution (0.8 nm laterally and 1.5 nm vertically) and single
      spin sensitivity. Our measurements uncover electronic spins on the diamond
      surface that can potentially be used as resources for improved magnetic imaging.
      This NV-MRI technique is immediately applicable to diverse systems including
      imaging spin chains, readout of spin-based quantum bits, and determining the
      location of spin labels in biological systems.

PMID- 24658169
TI  - Nanoscale MRI: dark spins in the spotlight.

PMID- 24658170
TI  - Random nanolasing in the Anderson localized regime.
AB  - The development of nanoscale optical devices for classical and quantum photonics
      is affected by unavoidable fabrication imperfections that often impose
      performance limitations. However, disorder may also enable new functionalities,
      for example in random lasers, where lasing relies on random multiple scattering.
      The applicability of random lasers has been limited due to multidirectional
      emission, lack of tunability, and strong mode competition with chaotic
      fluctuations due to a weak mode confinement. The regime of Anderson localization
      of light has been proposed for obtaining stable multimode random lasing, and
      initial work concerned macroscopic one-dimensional layered media. Here, we
      demonstrate on-chip random nanolasers where the cavity feedback is provided by
      the intrinsic disorder. The strong confinement achieved by Anderson localization
      reduces the spatial overlap between lasing modes, thus preventing mode
      competition and improving stability. This enables highly efficient, stable and
      broadband wavelength-controlled lasers with very small mode volumes. Furthermore,
      the complex interplay between gain, dispersion-controlled slow light, and
      disorder is demonstrated experimentally for a non-conservative random medium. The
      statistical analysis shows a way towards optimizing random-lasing performance by
      reducing the localization length, a universal parameter. 

PMID- 24658171
TI  - The effect of spin transport on spin lifetime in nanoscale systems.
AB  - Spintronics use the electron spin as a state variable for information processing
      and storage. This requires manipulation of spin ensembles for data encoding, and
      spin transport for information transfer. Because of the central importance of
      lifetime for understanding and controlling spins, mechanisms that determine this
      lifetime in bulk systems have been extensively studied. However, a clear
      understanding of few-spin systems remains challenging. Here, we report spatially
      resolved magnetic resonance studies of electron spin ensembles confined to a
      'spin nanowire' formed by nitrogen ion implantation in diamond. We measure the
      spin lifetime of the ensemble--that is, its spin autocorrelation time--by
      monitoring the statistical fluctuations of its net moment, which is in thermal
      equilibrium and has no imposed polarization gradient. We find that the lifetime
      of the ensemble is dominated by spin transport from the ensemble into the
      adjacent spin reservoir that is provided by the remainder of the nanowire. This
      is in striking contrast to conventional spin-lattice relaxation measurements of
      isolated spin ensembles. Electron spin resonance spectroscopy performed on
      nanoscale spin ensembles by means of a novel spin manipulation protocol
      corroborates spin transport in strong field gradients. Our experiments, supported
      by microscopic Monte Carlo modelling, provide a unique insight into the intrinsic
      dynamics of pure spin currents needed for nanoscale devices that seek to control
      spins.

PMID- 24658172
TI  - Electron-beam lithography: going green with silk.

PMID- 24658173
TI  - All-water-based electron-beam lithography using silk as a resist.
AB  - Traditional nanofabrication techniques often require complex lithographic steps
      and the use of toxic chemicals. To move from the laboratory scale to large
      scales, nanofabrication should be carried out using alternative procedures that
      are simple, inexpensive and use non-toxic solvents. Recent efforts have focused
      on nanoimprinting and the use of organic resists (such as quantum dot-polymer
      hybrids, DNA and poly(ethylene glycol)), which still require, for the most part,
      noxious chemicals for processing. Significant advances have been achieved using
      'green' resists that can be developed with water, but so far these approaches
      have suffered from low electron sensitivity, line edge roughness and scalability
      constraints. Here, we present the use of silk as a natural and biofunctional
      resist for electron-beam lithography. The process is entirely water-based,
      starting with the silk aqueous solution and ending with simple development of the
      exposed silk film in water. Because of its polymorphic crystalline structure,
      silk can be used either as a positive or negative resist through interactions
      with an electron beam. Moreover, silk can be easily modified, thereby enabling a
      variety of 'functional resists', including biologically active versions. As a
      proof of principle of the viability of all-water-based silk electron-beam
      lithography (EBL), we fabricate nanoscale photonic lattices using both neat silk
      and silk doped with quantum dots, green fluorescent proteins (GFPs) or
      horseradish peroxidase (HRP). 

PMID- 24658174
TI  - A novel chitosan-gammaPGA polyelectrolyte complex hydrogel promotes early new
      bone formation in the alveolar socket following tooth extraction.
AB  - A novel chitosan-gammaPGA polyelectrolyte complex hydrogel (C-PGA) has been
      developed and proven to be an effective dressing for wound healing. The purpose
      of this study was to evaluate if C-PGA could promote new bone formation in the
      alveolar socket following tooth extraction. An animal model was proposed using
      radiography and histomorphology simultaneously to analyze the symmetrical
      sections of Wistar rats. The upper incisors of Wistar rats were extracted and the
      extraction sockets were randomly treated with gelatin sponge, neat chitosan, C
      PGA, or received no treatment. The extraction sockets of selected rats from each
      group were evaluated at 1, 2, 4, or 6 wk post-extraction. The results of
      radiography and histopathology indicated that the extraction sockets treated with
      C-PGA exhibited lamellar bone formation (6.5%) as early as 2 wk after the
      extraction was performed. Moreover, the degree of new bone formation was
      significantly higher (P < 0.05) in the extraction sockets treated with C-PGA at 6
      wk post-extraction than that in the other study groups. In this study, we
      demonstrated that the proposed animal model involving symmetrical sections and
      simultaneous radiography and histomorphology evaluation is feasible. We also
      conclude that the novel C-PGA has great potential for new bone formation in the
      alveolar socket following tooth extraction. 

PMID- 24658175
TI  - A reductive ligation based fluorescent probe for S-nitrosothiols.
AB  - A reductive ligation based fluorescent probe () for the detection of S
      nitrosothiols (SNO) was developed. The probe showed good selectivity and
      sensitivity for SNO. 

PMID- 24658176
TI  - Sound management may sequester methane in grazed rangeland ecosystems.
AB  - Considering their contribution to global warming, the sources and sinks of
      methane (CH4) should be accounted when undertaking a greenhouse gas inventory for
      grazed rangeland ecosystems. The aim of this study was to evaluate the mitigation
      potential of current ecological management programs implemented in the main
      rangeland regions of China. The influences of rangeland improvement, utilization
      and livestock production on CH4 flux/emission were assessed to estimate CH4
      reduction potential. Results indicate that the grazed rangeland ecosystem is
      currently a net source of atmospheric CH4. However, there is potential to convert
      the ecosystem to a net sink by improving management practices. Previous
      assessments of capacity for CH4 uptake in grazed rangeland ecosystems have not
      considered improved livestock management practices and thus underestimated
      potential for CH4 uptake. Optimal fertilization, rest and light grazing, and
      intensification of livestock management contribute mitigation potential
      significantly. 

PMID- 24658177
TI  - Binder free three-dimensional sulphur/few-layer graphene foam cathode with
      enhanced high-rate capability for rechargeable lithium sulphur batteries.
AB  - A novel ultra-lightweight three-dimensional (3-D) cathode system for lithium
      sulphur (Li-S) batteries has been synthesised by loading sulphur on to an
      interconnected 3-D network of few-layered graphene (FLG) via a sulphur solution
      infiltration method. A free-standing FLG monolithic network foam was formed as a
      negative of a Ni metallic foam template by CVD followed by etching away of Ni.
      The FLG foam offers excellent electrical conductivity, an appropriate
      hierarchical pore structure for containing the electro-active sulphur and
      facilitates rapid electron/ion transport. This cathode system does not require
      any additional binding agents, conductive additives or a separate metallic
      current collector thus decreasing the weight of the cathode by typically ~20-30
      wt%. A Li-S battery with the sulphur-FLG foam cathode shows good electrochemical
      stability and high rate discharge capacity retention for up to 400
      discharge/charge cycles at a high current density of 3200 mA g(-1). Even after
      400 cycles the capacity decay is only ~0.064% per cycle relative to the early
      (e.g. the 5th cycle) discharge capacity, while yielding an average columbic
      efficiency of ~96.2%. Our results indicate the potential suitability of graphene
      foam for efficient, ultra-light and high-performance batteries. 

PMID- 24658178
TI  - Granulocyte/macrophage colony-stimulating factor influences angiogenesis by
      regulating the coordinated expression of VEGF and the Ang/Tie system.
AB  - Granulocyte/macrophage colony-stimulating factor (GM-CSF) can accelerate wound
      healing by promoting angiogenesis. The biological effects of GM-CSF in
      angiogenesis and the corresponding underlying molecular mechanisms, including in
      the early stages of primitive endothelial tubule formation and the later stages
      of new vessel maturation, have only been partially clarified. This study aimed to
      investigate the effects of GM-CSF on angiogenesis and its regulatory mechanisms.
      Employing a self-controlled model (Sprague-Dawley rats with deep partial
      thickness burn wounds), we determined that GM-CSF can increase VEGF expression
      and decrease the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2
      in the early stages of the wound healing process, which promotes the degradation
      of the basement membrane and the proliferation of endothelial cells. At later
      stages of wound healing, GM-CSF can increase the expression ratio of Ang-1/Ang-2
      and the phosphorylation of Tie-2 and maintain a high VEGF expression level.
      Consequently, pericyte coverages were higher, and the basement membrane became
      more integrated in new blood vessels, which enhanced the barrier function of
      blood vessels. In summary, we report here that increased angiogenesis is
      associated with GM-CSF treatment, and we indicate that VEGF and the Ang/Tie
      system may act as angiogenic mediators of the healing effect of GM-CSF on burn
      wounds. 

PMID- 24658179
TI  - Vestibular effects of a 7 Tesla MRI examination compared to 1.5 T and 0 T in
      healthy volunteers.
AB  - Ultra-high-field MRI (7 Tesla (T) and above) elicits more temporary side-effects
      compared to 1.5 T and 3 T, e.g. dizziness or "postural instability" even after
      exiting the scanner. The current study aims to assess quantitatively vestibular
      performance before and after exposure to different MRI scenarios at 7 T, 1.5 T
      and 0 T. Sway path and body axis rotation (Unterberger's stepping test) were
      quantitatively recorded in a total of 46 volunteers before, 2 minutes after, and
      15 minutes after different exposure scenarios: 7 T head MRI (n = 27), 7 T no RF
      (n = 22), 7 T only B0 (n = 20), 7 T in & out B0 (n = 20), 1.5 T no RF (n = 20), 0
      T (n = 15). All exposure scenarios lasted 30 minutes except for brief one minute
      exposure in 7 T in & out B0. Both measures were documented utilizing a 3D
      ultrasound system. During sway path evaluation, the experiment was repeated with
      eyes both open and closed. Sway paths for all long-lasting 7 T scenarios (normal,
      no RF, only B0) with eyes closed were significantly prolonged 2 minutes after
      exiting the scanner, normalizing after 15 minutes. Brief exposure to 7 T B0 or 30
      minutes exposure to 1.5 T or 0 T did not show significant changes. End positions
      after Unterberger's stepping test were significantly changed counter-clockwise
      after all 7 T scenarios, including the brief in & out B0 exposure. Shorter
      exposure resulted in a smaller alteration angle. In contrast to sway path,
      reversal of changes in body axis rotation was incomplete after 15 minutes. 1.5 T
      caused no rotational changes. The results show that exposure to the 7 Tesla
      static magnetic field causes only a temporary dysfunction or "over-compensation"
      of the vestibular system not measurable at 1.5 or 0 Tesla. Radiofrequency fields,
      gradient switching, and orthostatic dysregulation do not seem to play a role. 

PMID- 24658180
TI  - Estimating the risk of parvovirus B19 infection in blood donors and pregnant
      women in Japan.
AB  - BACKGROUND: Seroepidemiological study of parvovirus B19 has not taken place for
      some 20 years in Japan. To estimate the risk of parvovirus B19 infection in Japan
      among blood donors and pregnant women in this century, a seroepidemiological
      survey and statistical modeling of the force of infection were conducted.
      METHODOLOGY/PRINCIPAL FINDINGS: The time- and age-specific seroprevalence data
      were suggestive of strong age-dependency in the risk of infection. Employing a
      piecewise constant model, the highest forces of infection of 0.05 and 0.12 per
      year were observed among those aged 0-4 and 5-9 years, respectively, while
      estimates among older individuals were less than 0.01 per year. Analyzing the
      antigen detection data among blood donors, the age-specific proportion positive
      was highest among those aged 30-39 years, agreeing with the presence of dip in
      seroprevalence in this age-group. Among pregnant women, up to 107 fetal deaths
      and 21 hydrops fetalis were estimated to have occurred annually across Japan.
      CONCLUSIONS: Seroepidemiological profiles of PVB19 infection in Japan was
      characterized with particular emphasis on the risk of infection in blood donors
      and the burden of infection among pregnant women. When a vaccine becomes
      available in the future, a similar seroepidemiological study is expected to play
      a key role in planning the appropriate immunization policy.

PMID- 24658181
TI  - The paradigm of mutant p53-expressing cancer stem cells and drug resistance.
AB  - It is well accepted that expression of mutant p53 involves the gain of oncogenic
      specific activities accentuating the malignant phenotype. Depending on the
      specific cancer type, mutant p53 can contribute to either the early or the late
      events of the multiphase process underlying the transformation of a normal cell
      into a cancerous one. This multifactorial system is evident in ~50% of human
      cancers. Mutant p53 was shown to interfere with a variety of cellular functions
      that lead to augmented cell survival, cellular plasticity, aberration of DNA
      repair machinery and other effects. All these effects culminate in the
      acquisition of drug resistance often seen in cancer cells. Interestingly, drug
      resistance has also been suggested to be associated with cancer stem cells
      (CSCs), which reside within growing tumors. The notion that p53 plays a
      regulatory role in the life of stem cells, coupled with the observations that p53
      mutations may contribute to the evolvement of CSCs makes it challenging to
      speculate that drug resistance and cancer recurrence are mediated by CSCs
      expressing mutant p53.

PMID- 24658182
TI  - Genetic variants in DNA repair pathways and risk of upper aerodigestive tract
      cancers: combined analysis of data from two genome-wide association studies in
      European populations.
AB  - DNA repair pathways are good candidates for upper aerodigestive tract cancer
      susceptibility because of their critical role in maintaining genome integrity. We
      have selected 13 pathways involved in DNA repair representing 212 autosomal
      genes. To assess the role of these pathways and their associated genes, two
      European data sets from the International Head and Neck Cancer Epidemiology
      consortium were pooled, totaling 1954 cases and 3121 controls, with documented
      demographic, lifetime alcohol and tobacco consumption information. We applied an
      innovative approach that tests single nucleotide polymorphism (SNP)-sets within
      DNA repair pathways and then within genes belonging to the significant pathways.
      We showed an association between the polymerase pathway and oral cavity/pharynx
      cancers (P-corrected = 4.45 * 10(-) (2)), explained entirely by the association
      with one SNP, rs1494961 (P = 2.65 * 10(-) (4)), a missense mutation V306I in the
      second exon of HELQ gene. We also found an association between the cell cycle
      regulation pathway and esophagus cancer (P-corrected = 1.48 * 10(-) (2)),
      explained by three SNPs located within or near CSNK1E gene: rs1534891 (P = 1.27 *
      10(-) (4)), rs7289981 (P = 3.37 * 10(-) (3)) and rs13054361 (P = 4.09 * 10(-)
      (3)). As a first attempt to investigate pathway-level associations, our results
      suggest a role of specific DNA repair genes/pathways in specific upper
      aerodigestive tract cancer sites.

PMID- 24658184
TI  - A commentary on the role of molecular technology and automation in clinical
      diagnostics.
AB  - Historically, the identification of bacterial or yeast isolates has been based on
      phenotypic characteristics such as growth on defined media, colony morphology,
      Gram stain, and various biochemical reactions, with significant delay in
      diagnosis. Clinical microbiology as a medical specialty has embraced advances in
      molecular technology for rapid species identification with broad-range 16S rDNA
      polymerase chain reaction (PCR) and matrix-assisted laser desorption and/or
      ionization time of flight (MALDI-TOF) mass spectrometry demonstrated as accurate,
      rapid, and cost-effective methods for the identification of most, but not all,
      bacteria and yeasts. Protracted conventional incubation times previously
      necessary to identify certain species have been mitigated, affording patients
      quicker diagnosis with associated reduction in exposure to empiric broad-spectrum
      antimicrobial therapy and shortened hospital stay. This short commentary details
      such molecular advances and their implications in the clinical microbiology
      setting. 

PMID- 24658185
TI  - Gate tunable nonlinear rectification effects in three-terminal graphene
      nanojunctions.
AB  - We report on a study of the room-temperature nonlinear charge transport
      properties of three-terminal junction devices made from graphene. We demonstrate
      that the graphene three terminal junction devices show a rectification
      characteristic, namely, when voltages VL = V and VR = -V are applied to the left
      and the right terminal in a push-pull configuration, the voltage output from the
      central terminal VC is finite and is scaled approximately with V(2). The
      rectification coefficient can be effectively tuned by a gate voltage and shows a
      transport carrier polarity dependence. We further show that the nonlinear charge
      transport characteristics can be used to probe the electronic structure of
      graphene nanostructures and to study the thermoelectrical power of graphene.
      These results show that the graphene three-terminal junction devices could be
      used as novel building blocks for nanoelectronics and as novel devices for the
      study of the material properties of graphene on the nanoscale. 

PMID- 24658186
TI  - Fetal growth in pregnancies conceived after gastric bypass surgery in relation to
      surgery-to-conception interval: a Danish national cohort study.
AB  - OBJECTIVE: To describe early and late fetal growth in pregnancies conceived after
      gastric bypass surgery in relation to time from surgery to conception of
      pregnancy. METHODS: National cohort study on 387 Danish women, who had
      laparoscopic or open gastric bypass surgery prior to a singleton pregnancy in
      which first trimester screening was performed between January 2008 and June 2011.
      Data were derived from national registers (Danish National Registry of Patients
      and Danish National Birth Registry, Pregnancy Complications and Abortion-clinical
      quality database (PreCAb) and the Danish Fetal Medicine Database). Main outcome
      measures were early and late fetal growth in relation to time from bariatric
      surgery to conception of the pregnancy. Early fetal growth was expressed as
      "Fetal Growth Index": the ratio between the estimated number of days from first
      trimester ultrasound to second trimester ultrasound biometries and the actual
      calender time elapsed in days. Late fetal growth was expressed as the observed
      versus expected birthweight according to gestational age (GA). RESULTS: The
      surgery-to-conception interval ranged from 3 to 1851 days with a mean value of
      502 (SD, 351) days. The mean "fetal growth index" was 0.99 (SD, 0.02) days/day
      and thus significantly lower than in the background population (mean, 1.04 (SD,
      0.09) days/day, p<0.0001). The proportion of infants being small for gestational
      age was 18.8% and the proportion of large for gestational age infants was 6.7%.
      The correlation coefficients between surgery-to-conception time and "fetal growth
      index" and birthweight according to GA were 0.01 (p = 0.8) and 0.04 (p = 0.4),
      respectively. CONCLUSION: Fetal growth index was lower than reported in the
      background population. No correlation was found between the surgery-to-conception
      interval and early or late fetal growth in pregnancies conceived after gastric
      bypass surgery.

PMID- 24658187
TI  - Impaired fear extinction as displayed by serotonin transporter knockout rats
      housed in open cages is disrupted by IVC cage housing.
AB  - Anxiety disorders are influenced by both environmental and genetic factors. A
      well-known example for gene x environment interactions in psychiatry is the low
      activity (s) allelic variant of the serotonin transporter (5-HTT) promoter
      polymorphism (5-HTTLPR) that in the context of stress increases risk for
      depression and post-traumatic stress disorder (PTSD). Previously, we observed
      robust anxiety-related phenotypes, such as an impairment in fear extinction, in 5
      HTT knockout (5-HTT-/-) versus wild-type (5-HTT+/+) rats housed in open cages.
      Recently, housing conditions were changed from open cages to individually
      ventilated cages (IVC), which are associated with a high ventilation fold and
      noise. This switch in housing conditions prompted an unplanned 5-HTT gene x
      environment interaction study in our rats. The current study shows that lifetime
      stress by means of IVC cage housing abolished genotype differences in fear
      extinction between 5-HTT-/- and 5-HTT+/+ rats. Although this effect was not
      attributed specifically to either the 5-HTT+/+ or the 5-HTT-/- genotype, the
      findings are in agreement with the modulatory role of serotonin in the processing
      of environmental stimuli. Our findings also underline the possibility that
      housing conditions confound the interpretation of anxiety-related behaviours in
      rodents. 

PMID- 24658188
TI  - On-line haemodiafiltration after the ESHOL study.

PMID- 24658189
TI  - suPAR and focal segmental glomerulosclerosis.

PMID- 24658190
TI  - [Methodological approach to designing a telecare system for pre-dialysis and
      peritoneal dialysis patients].
AB  - BACKGROUND: A major obstacle that hinders the implementation of technological
      solutions in healthcare is the rejection of developed systems by users
      (healthcare professionals and patients), who consider that they do not adapt to
      their real needs. OBJECTIVES: (1) To design technological architecture for the
      telecare of nephrological patients by applying a methodology that prioritises the
      involvement of users (professionals and patients) throughout the design and
      development process; (2) to show how users' needs can be determined and addressed
      by means of technology, increasing the acceptance level of the final systems.
      METHODS: In order to determine the main current needs in Nephrology, a group of
      Spanish Nephrology Services was involved. Needs were recorded through semi
      structured interviews with the medical team and questionnaires for professionals
      and patients. RESULTS: A set of requirements were garnered from professionals and
      patients. In parallel, the group of biomedical engineers identified requirements
      for patient telecare from a technological perspective. All of these requirements
      drove the design of modular architecture for the telecare of peritoneal dialysis
      and pre-dialysis patients. CONCLUSIONS: This work shows how it is possible to
      involve users in the whole process of design and development of a system. The
      result of this work is the design of adaptable modular architecture for the
      telecare of nephrological patients and it addresses the preferences and needs of
      patient and professional users consulted.

PMID- 24658191
TI  - Designing a method to assess and improve the quality of healthcare in Nephrology
      by means of the Delphi technique.
AB  - BACKGROUND: Free choice is not easy when there is a lack of information. Methods
      for evaluating quality of care to provide patients with comprehensive and
      understandable information on hospital departments are therefore necessary.
      OBJECTIVES: To draft a methodological proposal for evaluating quality of care of
      hospital departments, the data of which can provide citizens with useful care
      quality information. The proposal should be based on consensus and on the
      experience of medical specialists, defining thus complementary paths to
      improvement. METHODS: A Delphi study on the quality of care in Nephrology,
      comprising three phases: assessment results, necessary means for quality, and
      importance of medical advice and surveys among specialists. The questionnaire was
      administered to a panel of 32 nephrologists. RESULTS: The nephrologists accepted
      the outcome criteria on quality of care 55/62 (89%), as well as the proposed
      means for quality of care 87/92 (95%). 81% of the nephrologists reported the
      validity and topicality of providing patients with specialist advice as to the
      most adequate department to better treat their kidney diseases. 86% of the
      panellists deemed appropriate to include surveys on medical advice as additional
      criteria for the evaluation of quality of care. CONCLUSIONS: It is possible to
      obtain a consensus-based methodological proposal for the evaluation and
      improvement of quality of care which includes results on quality of care, means
      for quality of care, and medical advice based on surveys carried out among
      specialists to identify the best Nephrology departments. This method could
      provide reliable and understandable guidance for citizens.

PMID- 24658192
TI  - Spanish nephrologists and the management of mineral and bone metabolism disorders
      in chronic kidney disease.
AB  - This study was designed to assess the current perception of Spanish nephrologists
      in the clinical management of mineral and bone metabolism disorders in chronic
      kidney disease (CKD-MBD). As such, we used a semi-structured distance
      professional consensus procedure via e-mail (modified Delphi method) on a
      representative nephrologist panel, under the direction of a coordinating
      committee. To analyse the group's opinion and the type of consensus reached on
      each issue raised, we used the median of the group's scores and the "level of
      agreement" reached by those surveyed. On a total of 86 issues, a consensus
      agreement and disagreement was achieved in 70 (81.4%), of which 60.5% (52 items)
      agreed with the statement and 20.9% (18 items) disagreed. In 16 items (18.6%),
      there was insufficient unanimity in the panel's opinion, either due to
      professional opinion disparity or due to the lack of opinion established in the
      majority of the expert committee. Accepting the study's limitations, we
      considered that the items for which there was a consensus reinforce some CKD-MBD
      concepts with their impact on daily clinical practice and allow the degree of
      homogeneity that we could expect in this area to be assessed. The items in which
      there was no consensus help us to know the areas of uncertainty and are very
      useful for clarifying which aspects have a greater need for further knowledge and
      which areas require prospective studies to be conducted to improve the management
      of these disorders.

PMID- 24658193
TI  - Prevalence of anaemia and its clinical management in patients with stages 3-5
      chronic kidney disease not on dialysis in Catalonia: MICENAS I study.
AB  - INTRODUCTION: Anaemia is a common complication of chronic kidney disease (CKD).
      The aim of this study was to determine the prevalence and clinical management of
      anaemia in patients with stages 3-5 CKD not on dialysis treated in outpatient
      Nephrology clinics (OC) in Catalonia. METHODS: Epidemiological, cross-sectional
      cohort, multicentre study under routine clinical practice conditions. Data
      collection by electronic data collection log-book (e-DCL) including personal
      information and data related to anaemia (haemoglobin, iron status, treatment with
      erythropoiesis-stimulating agents [ESA] and other anaemia treatments). Anaemia
      was defined as haemoglobin levels <13.5 g/dL in males or <12 g/dL in females or
      patients who receive treatment with ESA. RESULTS: We included 504 patients (56.4%
      male, mean age of 67.8 +/- 15.5 years): 61.5% had stage 3 CKD, 30.2% stage 4 and
      8.3% stage 5. The main causes of CKD were vascular and diabetic nephropathy. The
      prevalence of anaemia was 58.5% (n=295), however, only 14.9% of patients had
      haemoglobin levels <11 g/dL. Mean haemoglobin levels decreased and ESA treatment
      was more common as CKD progressed, but no significant differences were observed
      regarding the prescription of iron, according to CKD stages. ESA and intervals
      most frequently prescribed were darbepoetin alfa with a median dose of 40
      MUg/biweekly, followed by C.E.R.A. with a median dose of 75 MUg/month and epoetin
      beta with a median dose of 5,000 IU/week. Among the patients with anaemia
      (n=295), 36.3% (n=107) had iron deficiency and only 53.3% of these patients were
      treated with iron supplements. CONCLUSIONS: This study demonstrates the high
      prevalence of anaemia, which increases as the disease progresses and its good
      control in a CKD patient population treated in Nephrology outpatient clinics in
      Catalonia. This control is achieved with moderate doses of ESA and iron
      supplements prescribed in more than 50% of anaemic CKD patients.

PMID- 24658194
TI  - The effect of replacing aluminium hydroxide with calcium acetate/magnesium
      carbonate on serum phosphorus control in haemodialysis patients.
AB  - INTRODUCTION: Calcium acetate/magnesium carbonate (MgCO3) is a phosphorus binder
      with advantages in terms of cost, safety and tolerance and it has a similar
      efficacy to other drugs. The objective of the study is to assess the effects of
      replacing aluminium hydroxide [Al(OH3)] with MgCO3 on phosphorus and calcium
      metabolism in a cohort of haemodialysis patients. MATERIALS AND METHODS: We
      included 21 patients with phosphorus <5mg/dl, with Al(OH3) as the only binder.
      The conversion to MgCO3 was carried out without changing the number of pills. We
      recorded clinical-demographic characteristics, treatment for secondary
      hyperparathyroidism and laboratory parameters before conversion and every month
      for four months. RESULTS: Phosphataemia decreased from 4.52 +/- 0.99 to 4.02 +/-
      1.07 mg/dl (p=.027), and there was a decrease in the calcium-phosphorus product
      from 40.20 +/- 10.44 to 35.16 +/- 11.06 mg2/dl2 (p=.037). We did not observe
      significant changes in levels of calcium, parathyroid hormone or 25-OH-vitamin
      D3. The daily number of pills prescribed was reduced from 3.33 +/- 2.29 to 2.15
      +/- 2.21 (p=.020). Concomitant treatments were not altered. We observed an
      initial significant increase in magnesaemia from 2.21 +/- 0.24 to 2.43 +/- 0.39
      mg/dl (p=.001), which subsequently remained stable. We found a decrease in serum
      aluminium from 14.91 +/- 8.55 to 8.47 +/- 3.98 ug/l (p=.004), with levels within
      the recommended range in all patients. CONCLUSIONS: MgCO3 allowed good control of
      serum phosphorus in haemodialysis patients who were previously well controlled
      with Al(OH)3, using fewer daily pills. There was a slight increase in serum
      magnesium, without short-term clinical significance. We do not know the effects
      of this increase in the longer term.

PMID- 24658195
TI  - Cardiovascular risk in peritoneal dialysis - a Portuguese multicenter study.
AB  - BACKGROUND: Cardiovascular (CV) disease is the major cause of mortality in
      patients undergoing renal replacement therapy. The primary aim of the study was
      to evaluate the CV risk profile and prevalence of CV disease in patients on
      peritoneal dialysis (PD) in Portugal. The secondary goal was to establish
      parameters most associated with CV disease. METHODS: Retrospective, multicenter
      study of the prevalent adult population on PD. Six hundred patients were included
      (56.7% male; mean age 53.5 +/- 15.3 years), on PD for 25.6 +/- 21.9 months.
      Patients were divided into two groups: group 1 (n=166) with CV disease and group
      2 (n=434) without CV disease. Comparisons were made regarding traditional CV risk
      factors and those associated with uremia and PD itself, and a multivariate
      analysis was performed to determine variables independently associated with CV
      disease. RESULTS: At the end of the study, the prevalence of CV disease was 28%.
      At univariate analysis, group 1 presented a higher frequency of males (p<.01),
      older patients (p<.01), diabetics (p<.01), occurrence of left ventricular
      hypertrophy (LVH) (p<.01), mean C-reactive protein (CRP) (p=.04), lower mean
      parathormone level (p=.014), lower serum phosphorus (p=.02), lower daily urine
      output (p=.04), lower weekly Kt/V (p=.008), increased use of icodextrin and
      hypertonic glucose-based PD solutions (p<.001 and p=.006, respectively) and more
      were under continuous ambulatory PD (CAPD) (p=.014) and had a high peritoneal
      transport status (p=.02). Multivariate analysis provided a significant
      discriminatory influence pertaining to age >50 years, CRP>0.6 mg/dl, male gender,
      diabetes, LVH, CAPD and anuria, when comparing group 1 and group 2. CONCLUSIONS:
      Risk factors most related to the development of CV disease in PD in Portugal are
      age >50 years, CRP>0.6 mg/dL, male gender, diabetes, LVH, CAPD and anuria.

PMID- 24658196
TI  - Haptoglobin genotype and risk of diabetic nephropathy in patients with type 1
      diabetes mellitus: a study on a Spanish population.
AB  - BACKGROUND: Few reports have studied the possible association between the
      haptoglobin (Hp) genotype and the risk of diabetic nephropathy (DN) in type 1
      diabetes (T1D), with conflicting results to date. AIMS: To study whether the 2-2
      Hp genotype is associated with an increased risk of overt DN in a Spanish
      population with T1D. METHODS: We performed a case-control study in a Spanish
      population. CASES: T1D patients with end-stage renal disease (stage 5 of NKF
      KDOQI), awaiting reno-pancreatic transplantation or having already been
      transplanted (reno-pancreatic or renal alone). CONTROLS: T1D patients, matched
      for sex and time of diabetes evolution, with preserved renal function and normal
      urinary albumin excretion. Hp genotyping was done using polymerase chain reaction
      and electrophoresis. RESULTS: We included 57 cases and 57 controls in the study.
      There were no statistically significant differences in gender (70% vs. 61% males,
      p=1.0) or the duration of diabetes (23.0 +/- 6.7 vs. 20.8 +/- 9.3 years; p=0.1),
      although the age of onset of diabetes was lower in the cases (14.1 +/- 6.8 vs.
      17.7 +/- 10.1 years, p=0.03). The frequency of genotypes 1-1, 1-2 and 2-2 was
      19.3%, 42.1% and 38.6% in cases and 17.5%, 49.1% and 33.4% in controls,
      respectively, with no statistically significant differences between groups
      (p=0.8). Conditional logistic regression analysis showed no significant
      association between genotype 2-2 of Hp and the development of DN (OR 1.14, CI
      0.52-2.52). CONCLUSIONS: In our sample of a Spanish population with T1D, no
      association was found between the Hp genotype and risk of overt DN.

PMID- 24658197
TI  - Early steroid withdrawal in a renal transplant cohort treated with tacrolimus,
      mycophenolate mofetil and basiliximab.
AB  - BACKGROUND: Acute rejection and graft function have not been completely clarified
      in early-steroid-withdrawal (ESW) patients. The objective of this study was to
      compare the effect of early steroid withdrawal on GFR, graft survival/rejection
      in recipients in a cohort treated with tacrolimus/mycophenolate mofetil compared
      to a control cohort. MATERIAL AND METHOD: Retrospective cohort, in 60 low
      immunological risk recipients between December 2005 and July 2010. Study cohort
      (ESW-C N=32), steroid withdrawal was carried out after 5 days, while they were
      receiving tacrolimus/mycophenolate mofetil. The control cohort (C-C, N=28)
      received prednisone/tacrolimus/mycophenolate mofetil. Clinical, biochemical and
      histological variables were assessed at baseline and after 3, 6, and 12 months of
      follow-up. Kaplan-Meier and the Cox proportional hazards model were used to
      assess survival. Comparisons between cohorts were carried out by the Student's t
      and c2 tests. RESULTS: At follow-up, C-C displayed significantly higher systolic
      (125 +/- 10 vs. 114 +/- 8) and diastolic (81 +/- 8 vs. 72 +/- 7) blood pressure,
      serum glucose (96 +/- 13 vs. 86 +/- 10), triglycerides (177 +/- 61 vs. 129 +/-
      34), total (183 +/- 43 vs. 148 +/- 34) and LDL-cholesterol (100 +/- 22 vs. 87 +/-
      25). C-C had a higher proportion of antihypertensive (57 vs. 13%), and statins
      (27 vs. 9%) use. eGFR was better in ESW-C than in C-C (85.4 +/- 20.6 vs. 70.6 +/-
      17.0, p=.004). AR frequency was lower in ESW-C. CONCLUSIONS: Graft survival, GFR,
      AR rate and metabolic profile were better in the ESW-C than in C-C.

PMID- 24658198
TI  - Tables for estimating the glomerular filtration rate using the new CKD-EPI
      equation from serum creatinine concentration.
AB  - Chronic kidney disease (CKD) and its complications have become a major healthcare
      problem, both due to the resources that are required in the final stages of the
      disease and to secondary complications. As such, its early diagnosis is
      considered to be very important nowadays. The recently published 2013 KDIGO
      guidelines base the definition and classification of CKD on glomerular filtration
      values and albuminuria as staging criteria and prognostic markers of the disease.
      The MDRD and MDRD-IDMS equations (when creatinine values can be traced to the
      reference method) are those most used, but both the 2013 KDIGO international
      guidelines and the new 2013 CKD consensus document, in which ten scientific
      societies participated under the direction of the Spanish Society of Nephrology,
      recommend to be replaced by the CKD-EPI equation. Our objective has been, as with
      previous equations, to develop tables that display the estimated glomerular
      filtration rate value using the CKD-EPI equation from serum creatinine
      concentration, age and sex, and thereby provide an instrument that facilitates
      the dissemination of this new equation, particularly in settings where it is not
      calculated automatically. 

PMID- 24658199
TI  - Acute rejection of non-functional renal grafts in dialysis patients after
      starting treatment with interferon and ribavirin.

PMID- 24658200
TI  - Treatment of vascular access-related steal syndrome by means of juxta-anastomotic
      vein interposition of a prosthetic graft segment.
AB  - OBJECTIVE: Steal syndrome is a severe complication of vascular access. Our aim is
      to present the initial results of a simple and effective treatment: the
      interposition of a prosthetic segment in the juxta-anastomotic vein. METHOD:
      Between 2009 and 2012, 14 patients (57 % male, average age 71) with severe steal
      syndrome due to vascular access (stages II-IV), following a clinical and
      systematic echographic study and a selective angiographic study, were treated
      through the interposition of a 6 mm segment of PTFE in the juxta-anastomotic
      vein, in addition to selective patch repair of arterial stenosis (2 cases) or
      ligature of useless venous collaterals (8 cases). Local or regional anaesthesia
      was used and outpatient care was given in all cases. RESULTS: There was 100 %
      technical success. The pre- and post-operative echographical study showed a
      reduction of post-operative access flow by 39 % and an increase of radial artery
      flow by 477 %. Ischaemic symptoms were resolved in 12 patients (86 %); the other
      two patients required additional procedures due to persistent ischaemic symptoms.
      There was a post-operative venous rupture, which required a definitive ligation.
      No patient suffered amputations, nor were there losses or access thrombosis
      during the follow-up. The primary and primary-assisted patencies free of new
      ischemic symptoms were 78 % and 78 % at 12 months, and 62 % and 78 % at 24
      months. CONCLUSIONS: The interposition of a prosthetic segment in the juxta
      anastomotic vein is a simple, quick and effective technique in the treatment of
      vascular steal syndrome, with promising results at the 2 year follow-up.

PMID- 24658201
TI  - Consensus document for the detection and management of chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a major public health problem that, in its
      different stages, may affect up to 10% of the Spanish population and results in
      high morbidity and mortality, as well as high consumption of National Health
      System resources. Ten scientific societies involved in the management of kidney
      patients agreed to update the 2007 CKD consensus document. The current version is
      an abridged edition of the detailed general document, which can be consulted on
      the webpages of each signatory society. It includes the following aspects: CKD
      definition, epidemiology and risk factors and criteria on diagnosis, assessment
      and staging of CKD, albuminuria and glomerular filtration estimation. Progression
      factors and concept. Criteria for referral to Nephrology. Patient follow-up,
      attitudes and objectives by specialty. Prevention of nephrotoxicity. Detection of
      cardiovascular damage. Attitudes, lifestyle and treatment: management of high
      blood pressure, dyslipidaemia, hyperglycaemia, smoking, obesity, hyperuricaemia,
      anaemia and mineral and bone metabolism disorders. Coordinated follow-up by
      Primary Care &ndash; other specialties &ndash; Nephrology. Management of renal
      replacement therapy, haemodialysis, peritoneal dialysis and renal transplantation
      patients. Palliative treatment of terminal uraemia. We hope that this document
      will be very useful in the multidisciplinary management of CKD patients, in view
      of the updated recommendations. 

PMID- 24658202
TI  - Is there a difficulty in maintaining haemoglobin target levels in pre-dialysis
      patients treated with erythropoiesis-stimulating agents?

PMID- 24658203
TI  - Acute renal failure due to haemoglobinuria secondary to P antigen.

PMID- 24658204
TI  - Gitelman syndrome with hiponatremia, a rare presentation.

PMID- 24658205
TI  - Multigene involvement in congenital nephrotic syndrome.

PMID- 24658206
TI  - Multifactorial hypertension of nephro-urological aetiology. A case study.

PMID- 24658207
TI  - Rapid engineering of endothelial cell-lined vascular-like structures in in situ
      crosslinkable hydrogels.
AB  - Fabrication of perfusable vascular networks in vitro is one of the most critical
      challenges in the advancement of tissue engineering. Because cells consume oxygen
      and nutrients during the fabrication process, a rapid fabrication approach is
      necessary to construct cell-dense vital tissues and organs, such as the liver. In
      this study, we propose a rapid molding process using an in situ crosslinkable
      hydrogel and electrochemical cell transfer for the fabrication of perfusable
      vascular structures. The in situ crosslinkable hydrogel was composed of hydrazide
      modified gelatin (gelatin-ADH) and aldehyde-modified hyaluronic acid (HA-CHO). By
      simply mixing these two solutions, the gelation occurred in less than 20 s
      through the formation of a stable hydrazone bond. To rapidly transfer cells from
      a culture surface to the hydrogel, we utilized a zwitterionic oligopeptide, which
      forms a self-assembled molecular layer on a gold surface. Human umbilical vein
      endothelial cells adhering on a gold surface via the oligopeptide layer were
      transferred to the hydrogel within 5 min, along with electrochemical desorption
      of the oligopeptides. This approach was applicable to cylindrical needles 200-700
      um in diameter, resulting in the formation of perfusable microchannels where the
      internal surface was fully enveloped with the transferred endothelial cells. The
      entire fabrication process was completed within 10 min, including 20 s for the
      hydrogel crosslinking and 5 min for the electrochemical cell transfer. This rapid
      fabrication approach may provide a promising strategy to construct perfusable
      vasculatures in cell-dense tissue constructs and subsequently allow cells to
      organize complicated and fully vascularized tissues while preventing hypoxic cell
      injury.

PMID- 24658208
TI  - The fate of Rose Anna Shedlock (c1850-1878) and the early career of Emile Roux
      (1853-1933).
AB  - The 1878 marriage of Rose Anna Shedlock and Emile Roux was a closely guarded
      secret. Shedlock studied medicine at Edinburgh with Sophia Jex-Blake (1840-1912)
      and her fellow students but is not mentioned by name in the usual accounts of
      their battle for recognition by the University. Subsequently Shedlock attended
      the Paris medical school where she probably met Emile Roux who was attached to
      the military medical school of the Val-de-Grace before his dismissal in 1876.
      Documentation of this episode and of Roux's life over the next two years is
      fragmentary and inaccurate. Sadly, Shedlock died, probably of tuberculosis, in
      1879. In a romanticized and highly inaccurate biography Roux's niece suggested
      that Rose Anna contracted tuberculosis from Roux whose life was later blighted by
      the disease. However, Shedlock was unwell for some years before they married and
      it seems far more likely that she passed the disease on to him. 

PMID- 24658209
TI  - Edward Flatau (1868-1932), Samual Goldflam (1852-1932) and Jozef Babinski (1857
      1932): Polish pioneers in neurology.
AB  - Flatau, Goldflam and Babinski originated from the Russian area of partitioned
      Poland in the 19th century and knew each other. Each contributed significantly to
      neurology at a time of adversity in Polish academic life because of the political
      situation. This paper in the main is centred on Flatau and Goldflam; Babinski,
      the most recognised of the three, is included for comparison. They all died in
      1932, when Poland had been an independent sovereignty since the end of the First
      World War in 1918. 

PMID- 24658210
TI  - Queen Anne (1665-1714) and her health.
AB  - The contemporary records of Queen Anne's health and disease are reviewed,
      including the strange diagnoses made and the treatments prescribed. A correct
      diagnosis is suggested. 

PMID- 24658211
TI  - The letters of Alix Joffroy (1844-1908), a medical intern at Lariboisiere's
      Hospital at the time of the Commune of Paris.
AB  - Since opening in 1848, Lariboisiere's Hospital was strongly associated with the
      history of Paris and especially with the terrible days of the siege of Paris and
      the fights of the Commune. On the day after the surrender, Alix Joffroy wrote his
      first letter to his mother. He described the events as he experienced them,
      expressing his feelings about the causes of this political and military disaster
      and his experience there as an intern. Some weeks after the defeat of France by
      the Prussians, humbled Parisians attacked governmental troops. From March to May
      1871 an improvised insurrectionary movement, The Commune of Paris, had taken
      power in the capital During the Bloody Week from 21 to 28 May 1871; this movement
      was suppressed by the Versaillaise Army. In his second letter, Joffroy related
      with great realism the tooth and nail fighting at the barricades and then the
      savage repression by the Army of the Communards around Lariboisiere's Hospital.
      Two letters preciously preserved by Alix Joffroy's descendants give this man's
      unique direct account of a tragic period of the 19th century. 

PMID- 24658212
TI  - Elizabeth Gaskell (1810-1865) and the medical world.
AB  - Elizabeth Gaskell had several relatives who were doctors, two of whom became well
      known, and she met many practitioners and specialists. This led to interesting
      portraits of doctors in her novels and also leads to speculation as to why she
      includes some real individuals and certain diagnoses and why she gave herself a
      poor prognosis. 

PMID- 24658213
TI  - Akhawayni (?-983 AD): A Persian neuropsychiatrist in the early medieval era (9th
      12th Century AD).
AB  - The early medieval era is also called the Islamic Golden Age because of the
      significant rise in sciences, including medicine. Abu Bakr Rabi' ibn Ahmad
      Akhawayni Bukhari (better known as Akhawayni) was one of the notable medical
      practitioners in his lifetime. His fame was in neuroscience and he became known
      as Pezeshk-e-Divanegan (Physician to the Insane). His only surviving book,
      Hidayat al-Muta'allimin fi al-Tibb (The Students' Handbook of Medicine), is the
      first medical textbook in Persian, after Islam. Akhawayni gathered and
      categorized available knowledge on neuropsychiatry and added his own. He was the
      first to describe sleep paralysis and to suggest pragmatic rather than
      supernatural treatment. He was also the first to present fever cure and his
      descriptions of meningitis (Lisarghos in Hidayat), mania, psychosis (Malikhulia),
      dementia (Ghotrab), etc., are close to current concepts. 

PMID- 24658214
TI  - Virchow's triad: Kussmaul, Quincke and von Recklinghausen.
AB  - For most of the 19th century, Germany was the centre of the medical world. From
      there the most innovating research came and many of the physicians of that era
      are known to nearly every medical student and physician of today. Virchow,
      Kussmaul, Quincke, von Recklinghausen, Muller and Schonlein are familiar names in
      today's medicine but insofar as they are merely eponyms associated with signs,
      symptoms, disease and anatomy. The story of their lives, their research and their
      influence on each other has been little examined. This is an essay about
      Virchow's relationship with his mentors Muller and Schonlein and how these
      relationships shaped the development of Kussmaul, Quincke and von Recklinghausen
      as students of Virchow and their work in medicine and clinical observation after
      leaving Virchow's laboratory. 

PMID- 24658215
TI  - Inspirations in medical genetics.
AB  - There are abundant instances in the history of genetics and medical genetics to
      illustrate how curiosity, charisma of mentors, nature, art, the saving of lives
      and many other matters have inspired great discoveries. These achievements from
      deciphering genetic concepts to characterizing genetic disorders have been
      crucial for management of the patients. There remains, however, a long pathway
      ahead. 

PMID- 24658216
TI  - Humphry Fortescue Osmond (1917-2004), a radical and conventional psychiatrist:
      The transcendent years.
AB  - This article describes the life and work of the psychiatrist Humphry Osmond who
      pursued a radical path as a psychiatrist while he remained within the
      establishment. To the public mind however, he is best known as the man who
      introduced Aldous Huxley to mescaline and coined the iconic word psychedelic.
      From an early stage of his career, Henry Osmond embraced new ideas to break the
      nexus in psychiatry at a time when neither biological nor psychoanalytic
      treatments were shown to have much benefit. To do this, he joined the radical
      social experiment in health in the Canadian province of Saskatchewan where he
      initiated a range of innovations that attracted international attention, as well
      as controversy over his espousal of the use of hallucinogens better to understand
      the experiences of psychotic patients. 

PMID- 24658217
TI  - Edward Leicester Atkinson (1881-1929): Antarctic explorer, scientist and naval
      surgeon.
AB  - Edward Leicester Atkinson qualified at St Thomas's Hospital in 1906 and joined
      the Navy in 1908. He was a doctor and parasitologist on Captain Scott's Terra
      Nova expedition to the Antarctic and had to take charge of the expedition when
      Scott died on his return from the South Pole. After the expedition he went to
      China and discovered the cause of schistosomiasis, returning at the start of the
      First World War in which he served with distinction, winning a DSO and Albert
      Medal but also being severely injured. After the war he served in various naval
      posts and became the youngest Surgeon Captain in the Navy before being retired on
      health grounds in 1928. He died at sea the following year. 

PMID- 24658218
TI  - Vallejo-Nagera (1926-1990) and the concept of 'soteric neurosis': a forgotten
      sketch of hoarding disorder in the obsessive-compulsive spectrum literature.
AB  - Juan Antonio Vallejo-Nagera, psychiatrist, painter and writer, wrote a widely
      adopted textbook of psychiatry in Spanish- and Portuguese-speaking countries,
      particularly during the 1970s, the famous Introduccion a la psiquiatria. There,
      he advanced the concept of soteric neurosis, a condition regarded as a 'mirror
      image' of phobias and similar to the diagnostic entity described in DSM-5 under
      the heading of hoarding disorder. Indeed, much earlier than the recent
      nosological discussions on hoarding, Vallejo-Nagera already reported soteric
      neurosis to be distinct from obsessive-compulsive disorder and to be associated
      with excessive attachment to objects and positive affect (pleasure), leading to
      accumulation, decreased treatment seeking, increasing interference in daily
      activities and blurred boundaries with normality. Vallejo-Nagera also made
      several predictions, including the propensity soteric neurosis patients may have
      towards the development of separation anxiety, obesity and other 'masked'
      symptoms. In the light of his original and insightful contributions to the
      concept of hoarding disorder, it would be interesting to assess his hypotheses in
      future studies. 

PMID- 24658220
TI  - Normative data and predictors of leg muscle function and postural control in
      children.
AB  - INTRODUCTION: At the present there are limited tools available to measure muscle
      function in young children. Ground reaction force plates measure lower-body
      function and postural control in older children and adults. The purpose of this
      study was threefold: 1) develop normative data for evaluating global muscle
      development; 2) determine the reproducibility of ground reaction force plates for
      assessing muscle function in preschool-age children; and 3) identify predictors
      of skeletal muscle function. METHODS: Children's (n = 81, 1.8 to 6.0 yr; M = 52%)
      muscle function and postural control was measured for jump (JMP), sit-to-stand
      (STS), and both undistracted and distracted body sway tests using a ground
      reaction force plate (Kistler 9200A). Whole body composition used dual-energy x
      ray absorptiometry (Hologic 4500A Discovery Series). Plasma 25-hydroxyvitamin D
      [25(OH)D] and parathyroid hormone concentrations were measured by
      chemiluminescence (Liaison, Diasorin, Mississauga, ON, Canada) as well as ionized
      calcium (ABL80 FLEX, Radiometer Medical A/S). Demographics, and anthropometry
      were collected. ANOVA and linear regression were used to identify predictors.
      Reproducibility was assessed by intersubject coefficient of variation. RESULTS:
      Age was a consistent predictor in all models; body size or fat and lean mass were
      important predictors in 3 of the models - STS peak force, STS peak power, and JMP
      peak power. STS was the most reproducible maneuver (average coefficient of
      variation =15.7%). Distracted body sway testing was not appropriate in these
      youngsters. CONCLUSION: The novel data presented in this study demonstrate a
      clear age (developmental) effect without any effect of sex on muscle function and
      postural control in young children. Lean muscle mass was important in some models
      (STS peak force and JMP peak power). The STS test was the best of the 4
      maneuvers.

PMID- 24658219
TI  - Ribosomal proteins as unrevealed caretakers for cellular stress and genomic
      instability.
AB  - Ribosomal proteins (RPs) have gained much attention for their extraribosomal
      functions particularly with respect to p53 regulation. To date, about fourteen
      RPs have shown to bind to MDM2 and regulate p53. Upon binding to MDM2, the RPs
      suppress MDM2 E3 ubiquitin ligase activity resulting in the stabilization and
      activation of p53. Of the RPs that bind to MDM2, RPL5 and RPL11 are the most
      studied and RPL11 appears to have the most significant role in p53 regulation.
      Considering that more than 17% of RP species have been shown to interact with
      MDM2, one of the questions remains unresolved is why so many RPs bind MDM2 and
      modulate p53. Genes encoding RPs are widely dispersed on different chromosomes in
      both mice and humans. As components of ribosome, RP expression is tightly
      regulated to meet the appropriate stoichiometric ratio between RPs and rRNAs.
      Once genomic instability (e.g. aneuploidy) occurs, transcriptional and
      translational changes due to change of DNA copy number can result in an imbalance
      in the expression of RPs including those that bind to MDM2. Such an imbalance in
      RP expression could lead to failure to assemble functional ribosomes resulting in
      ribosomal stress. We propose that RPs have evolved ability to regulate MDM2 in
      response to genomic instability as an additional layer of p53 regulation. Full
      understanding of the biological roles of RPs could potentially establish RPs as a
      novel class of therapeutic targets in human diseases such as cancer. 

PMID- 24658221
TI  - Ethanol does not delay muscle recovery but decreases testosterone/cortisol ratio.
AB  - PURPOSE: This study investigated the effects of ethanol consumption on recovery
      from traditional resistance exercise in recreationally trained individuals.
      METHODS: Nine recreationally trained volunteers (eight males and one female, 26
      +/- 4 yr, 81 +/- 4 kg) conducted four resistance exercise sessions and consumed a
      low (0.6 (females) and 0.7 (males) g . kg(-1) body mass) or a high dose (1.2 or
      1.4 g . kg(-1) body mass) of ethanol 1-2.5 h after exercise on two occasions. The
      first session was for familiarization with the tests and exercises and was
      performed without ethanol consumption. As a control trial, alcohol-free drinks
      were consumed after the exercise session. The sequence of trials, with low and
      high ethanol doses and alcohol-free drinks (control), was randomized. Maximal
      voluntary contractions (MVC) (knee extension), electrically stimulated
      contractions (knee extension), squat jumps, and hand grip strength were assessed
      10-15 min and 12 and 24 h after the ethanol/placebo drinks. In addition to a
      baseline sample, blood was collected 1, 12, and 24 h after the ethanol/placebo
      drinks. The exercise session comprised 4 * 8 repetition maximum of squats, leg
      presses, and knee extensions. RESULTS: MVC were reduced by 13%-15% immediately
      after the exercise sessions (P < 0.01). MVC, electrically stimulated force, and
      squat jump performance were recovered 24 h after ethanol drinks. MVC was not
      fully recovered at 24 h in the control trial. Compared with those in the control,
      cortisol increased and the free testosterone/cortisol ratio were reduced after
      the high ethanol dose (P < 0.01). CONCLUSIONS: Neither a low nor a high dose of
      ethanol adversely affected recovery of muscle function after resistance exercise
      in recreationally strength-trained individuals. However, the increased cortisol
      levels and reduced testosterone/cortisol ratio after the high ethanol dose could
      translate into long-term negative effects.

PMID- 24658222
TI  - Exercise training augments regional bone and marrow blood flow during exercise.
AB  - INTRODUCTION: The principal nutrient artery to the femur demonstrates an increase
      in nitric oxide-mediated vasodilation in rats after treadmill exercise training.
      The present study sought to determine whether exercise training improves hindlimb
      bone and marrow blood flow distribution at rest and during exercise. METHODS: Six
      8-month old male Sprague-Dawley rats were exercise trained (ET) with treadmill
      walking at 15 m . min(-1) up a 15 degrees  incline for 60 min . d(-1) over a 10-
      to 12-wk period. Sedentary (SED) control animals were acclimated to treadmill
      exercise for 5 min . d(-1) during the week preceding the blood flow measurements.
      Blood flow to nine distinct regions of the femur, tibia, and fibula was
      determined at rest and during low-intensity exercise (15 m . min(-1) walking, 0
      degrees  incline) using the reference sample microsphere method. RESULTS: The
      results demonstrate an augmentation of exercise hyperemia above that observed in
      SED rats during exercise in only one region of the bone, the femoral diaphysis,
      of ET rats. However, whereas exercise hyperemia occurred in three of the nine
      hindlimb bone regions measured in SED rats, exercise hyperemia occurred in seven
      of nine regions in ET rats. CONCLUSIONS: These data indicate an increase in
      generalized hindlimb bone and marrow blood flow during physical activity after a
      period of exercise training. Elevations in regional bone and marrow blood flow
      after training may augment medullary pressure and bone interstitial fluid flow,
      thus benefiting bone integrity.

PMID- 24658223
TI  - IR spectroscopy of pyridine-water structures in helium nanodroplets.
AB  - We present the results of an IR spectroscopic study of pyridine-water heterodimer
      formation in helium nanodroplets. The experiments were carried out in the
      frequency range of the pyridine C-H stretch region (3055-3100 cm(-1)) and upon
      water deuteration in the D-O stretch region (2740-2800 cm(-1)). In order to come
      to an unambiguous assignment we have determined the angle between the permanent
      dipole and the vibrational transition moment of the aggregates. The experiments
      have been accompanied by theoretical simulations which yielded two minimum
      structures with a 16.28 kJ mol(-1) energy difference. The experimentally observed
      bands were assigned to two structures with different H-bonds: an N...H bond and a
      bifurcated O...H-C bond.

PMID- 24658224
TI  - Helical folding of alpha/beta-peptides containing beta-amino acids with an eight
      membered ring constraint.
AB  - alphabetaalpha-Tripeptide that contains a cyclic beta-amino acid with an eight
      membered ring, a cis-2-aminocyclooct-5-enecarboxylic acid (cis-ACOE) or a cis-2
      aminocyclooctanecarboxylic acid (cis-ACOC) displayed an 11/9-helical turn in the
      crystal state. The related alpha/beta-peptide oligomers were shown to adopt 11/9
      helical conformations in solution. 

PMID- 24658225
TI  - An alternative suite of universal primers for genotyping in multiplex PCR.
AB  - The universal primer three-primer approach can dramatically reduce the cost when
      genotyping the microsatellites. One former research reported four universal
      primers that can be used in singleplex and multiplex genotyping. In this study,
      we proposed an alternative suite of universal primers with four dyes for
      genotyping 8-12 loci in one single run. This multiplex method was tested on
      Tetranychus truncatus. Published microsatellite loci of T. kanzawai,
      Frankliniella occidentalis and Nilaparvata lugens were modified as needed and
      also tested. The robustness of the method was confirmed by comparing with
      singleplex using multiple fluorophores and genotyping two populations of T.
      truncatus. This method showed lower signal strength than the singleplex three
      primer system, but it was still sufficient to determine the fragment length. The
      cost of such a project can be reduced dramatically when many loci of different
      species are involved. In this way, laboratories performing population genetic
      analyses or studying several different species may benefit from the use of this
      cost-effective protocol. 

PMID- 24658226
TI  - Gradient-based reliability maps for ACM-based segmentation of hippocampus.
AB  - Automatic segmentation of deep brain structures, such as the hippocampus (HC), in
      MR images has attracted considerable scientific attention due to the widespread
      use of MRI and to the principal role of some structures in various mental
      disorders. In this literature, there exists a substantial amount of work relying
      on deformable models incorporating prior knowledge about structures' anatomy and
      shape information. However, shape priors capture global shape characteristics and
      thus fail to model boundaries of varying properties; HC boundaries present rich,
      poor, and missing gradient regions. On top of that, shape prior knowledge is
      blended with image information in the evolution process, through global weighting
      of the two terms, again neglecting the spatially varying boundary properties,
      causing segmentation faults. An innovative method is hereby presented that aims
      to achieve highly accurate HC segmentation in MR images, based on the modeling of
      boundary properties at each anatomical location and the inclusion of appropriate
      image information for each of those, within an active contour model framework.
      Hence, blending of image information and prior knowledge is based on a local
      weighting map, which mixes gradient information, regional and whole brain
      statistical information with a multi-atlas-based spatial distribution map of the
      structure's labels. Experimental results on three different datasets demonstrate
      the efficacy and accuracy of the proposed method. 

PMID- 24658227
TI  - Noninvasive diabetes mellitus detection using facial block color with a sparse
      representation classifier.
AB  - Diabetes mellitus (DM) is gradually becoming an epidemic, affecting almost every
      single country. This has placed a tremendous amount of burden on governments and
      healthcare officials. In this paper, we propose a new noninvasive method to
      detect DM based on facial block color features with a sparse representation
      classifier (SRC). A noninvasive capture device with image correction is initially
      used to capture a facial image consisting of four facial blocks strategically
      placed around the face. Six centroids from a facial color gamut are applied to
      calculate the facial color features of each block. This means that a given facial
      block can be represented by its facial color features. For SRC, two
      subdictionaries, a Healthy facial color features subdictionary and DM facial
      color features subdictionary, are employed in the SRC process. Experimental
      results are shown for a dataset consisting of 142 Healthy and 284 DM samples.
      Using a combination of the facial blocks, the SRC can distinguish Healthy and DM
      classes with an average accuracy of 97.54%. 

PMID- 24658228
TI  - Atrial electrical activity detection using linear combination of 12-lead ECG
      signals.
AB  - ECG analysis is the method for cardiac arrhythmia diagnosis. During the
      diagnostic process many features should be taken into consideration, such as
      regularity and atrial activity. Since in some arrhythmias, the atrial electrical
      activity (AEA) waves are hidden in other waves, and a precise classification from
      surface ECG is inapplicable, a confirmation diagnosis is usually performed during
      an invasive procedure. In this paper, we study a "semiautomatic" method for AEA
      waves detection using a linear combination of 12-lead ECG signals. This method's
      objective is to be applicable to a variety of arrhythmias with emphasis given to
      detect concealed AEA waves. It includes two variations--using maximum energy
      ratio and a synthetic AEA signal. In the former variation, an energy ratio-based
      cost function is created and maximized using the gradient ascent method. The
      latter variation adapted the linear combiner method, when applied on a synthetic
      signal, combined with surface ECG leads. A study was performed evaluating the AEA
      waves detection from 63 patients (nine training, 54 validation) presenting eight
      arrhythmia types. Averaged sensitivity of 92.21% and averaged precision of 92.08%
      were achieved compared to the definite diagnosis. In conclusion, the presented
      method may lead to early and accurate detection of arrhythmias, which will result
      in a better oriented treatment. 

PMID- 24658229
TI  - Improving accuracy and precision of glucose sensor profiles: retrospective
      fitting by constrained deconvolution.
AB  - Frequent and accurate reference measurements of blood-glucose (BG) concentration
      are key for modeling and for computing outcome metrics in clinical trials but
      difficult, invasive, and costly to collect. Continuous glucose monitoring (CGM)
      is a minimally-invasive technology that has the requested temporal resolution to
      substitute BG references for such a scope, but still lacks of precision and
      accuracy. In this paper, we propose an algorithm that retrospectively
      reconstructs a reliable continuous-time BG profile for the aforementioned
      purposes, by simultaneously exploiting the high accuracy of (possibly sparse) BG
      references and the high temporal resolution of CGM data. The algorithm performs a
      constrained semiblind deconvolution in two steps: first, it estimates the unknown
      parameters of a model accounting for plasma-interstitum diffusion and sensor
      inaccurate calibration; then, it estimates BG performing a regularized
      deconvolution of CGM data, subject to the additional constraint that the
      reconstructed BG profile has to lay within the confidence interval of the
      available BG references. The algorithm was tested on 24 datasets collected in a
      20 h clinical trial where CGM records and a median of 13 BG samples per day were
      available. Mean absolute relative deviation was reduced (from 15.71% to 8.84%)
      with respect to unprocessed CGM and so did the error in the evaluation of the
      outcomes metrics (e.g., halved the error in the time-in-hypo assessment). The
      reconstructed BG profile, in view of its improved accuracy and precision, is
      suitable for clinical trial assessment, modeling and other offline applications. 

PMID- 24658230
TI  - Reduced computational models of serotonin synthesis, release, and reuptake.
AB  - Multiscale computational models can provide systemic evaluation and prediction of
      neuropharmacological drug effects. To date, little computational modeling work
      has been done to bridge from intracellular to neuronal circuit level. A complex
      model that describes the intracellular dynamics of the presynaptic terminal of a
      serotonergic neuron has been previously proposed. By systematically perturbing
      the model's components, we identify the slow and fast dynamical components of the
      model, and the reduced slow or fast mode of the model is computationally
      significantly more efficient with accuracy not deviating much from the original
      model. The reduced fast-mode model is particularly suitable for incorporating
      into neurobiologically realistic spiking neuronal models, and hence for large
      scale realistic computational simulations. We also develop user-friendly software
      based on the reduced models to allow scientists to rapidly test and predict
      neuropharmacological drug effects at a systems level. 

PMID- 24658231
TI  - A novel reduced-order prioritized optimization method for radiation therapy
      treatment planning.
AB  - In this study, a novel reduced order prioritized algorithm is presented for
      optimization in radiation therapy treatment planning. The proposed method
      consists of three stages. In the first stage, the intensity space was sampled by
      solving a series of unconstrained optimization problems. The objective function
      of the first stage is expressed as a scalarized weighted sum of partial
      objectives for the target and organ at risk. Latin hypercube sampling was
      utilized to define the weights for each run of the unconstrained optimizations.
      In the second stage, principal component analysis is applied to the solutions
      determined in the first stage to identify the major eigen modes in the
      intensities space, significantly reducing the number of independent variables. In
      the third stage, treatment planning goals/objectives are prioritized, and the
      problem is solved in the reduced order space. After each objective is optimized,
      that objective function is converted into a constraint for the lower-priority
      objectives. In the current formulation, a slip factor is used to relax the hard
      constraints for planning target volume (PTV) coverage. The applicability of the
      proposed method is demonstrated for one prostate and one lung intensity-modulated
      radiation therapy treatment plan. Upon completion of the sequential prioritized
      optimization, the mean dose at the rectum and bladder was reduced by 21.3% and
      22.4%, respectively. Additionally, we investigated the effect of the slip factor
      's' on PTV coverage and we found minimal degradation of the tumor dose (~4%).
      Finally, the speed up factors upon the dimensionality reduction were as high as
      49.9 without compromising the quality of the results. 

PMID- 24658232
TI  - An effective procedure for MNP-enhanced breast cancer microwave imaging.
AB  - Magnetic nanoparticles-enhanced microwave imaging has been recently proposed to
      overcome the limitations of conventional microwave imaging methods for breast
      cancer monitoring. In this paper, we discuss how to tackle the linear inverse
      scattering problem underlying this novel technique in an effective way. In
      particular, our aim is to minimize the required a priori patient-specific
      information, avoid occurrence of false positives, and keep the computational
      burden low. By relying on an extensive numerical analysis in realistic
      conditions, we show that the method can provide accurate and reliable images
      without information on the inner structure of the inspected breast and with an
      only rough knowledge of its shape. Notably, this allows moving to an offline
      stage the computationally intensive part of the image formation procedure. In
      addition, we show how to appraise the total amount of magnetic contrast agent
      targeted in the tumor. 

PMID- 24658233
TI  - Compression in wearable sensor nodes: impacts of node topology.
AB  - Wearable sensor nodes monitoring the human body must operate autonomously for
      very long periods of time. Online and low-power data compression embedded within
      the sensor node is therefore essential to minimize data storage/transmission
      overheads. This paper presents a low-power MSP430 compressive sensing
      implementation for providing such compression, focusing particularly on the
      impact of the sensor node architecture on the compression performance.
      Compression power performance is compared for four different sensor nodes
      incorporating different strategies for wireless transmission/on-sensor-node local
      storage of data. The results demonstrate that the compressive sensing used must
      be designed differently depending on the underlying node topology, and that the
      compression strategy should not be guided only by signal processing
      considerations. We also provide a practical overview of state-of-the-art sensor
      node topologies. Wireless transmission of data is often preferred as it offers
      increased flexibility during use, but in general at the cost of increased power
      consumption. We demonstrate that wireless sensor nodes can highly benefit from
      the use of compressive sensing and now can achieve power consumptions comparable
      to, or better than, the use of local memory. 

PMID- 24658235
TI  - Scattering transform for intrapartum fetal heart rate variability fractal
      analysis: a case-control study.
AB  - Intrapartum fetal heart rate monitoring, aiming at early acidosis detection,
      constitutes an important public health stake. Scattering transform is proposed
      here as a new tool to analyze intrapartum fetal heart rate (FHR) variability. It
      consists of a nonlinear extension of the underlying wavelet transform, that thus
      preserves its multiscale nature. Applied to an FHR signal database constructed in
      a French academic hospital, the scattering transform is shown to permit to
      efficiently measure scaling exponents characterizing the fractal properties of
      intrapartum FHR temporal dynamics, that relate not only to the sole covariance
      (correlation scaling exponent), but also to the full dependence structure of data
      (intermittency scaling exponent). Such exponents are found to satisfactorily
      discriminate temporal dynamics of healthy subjects (from that of nonhealthy ones)
      and to emphasize the role of the highest frequencies (around and above 1 Hz) in
      intrapartum FHR variability. This permits us to achieve satisfactory
      classification performance that improves on those obtained from the analysis of
      International Federation of Gynecology and Obstetrics (FIGO) criteria, notably by
      classifying as healthy a number of subjects that were incorrectly classified as
      nonhealthy by classical clinically used FIGO criteria. Combined to obstetrician
      annotations, these scaling exponents enable us to sketch a typology of these FIGO
      false positive subjects. Also, they permit us to monitor the evolution along time
      of the intrapartum health status of the fetuses and to estimate an optimal
      detection time-frame. 

PMID- 24658234
TI  - Evaluation of statistical inference on empirical resting state fMRI.
AB  - Modern statistical inference techniques may be able to improve the sensitivity
      and specificity of resting state functional magnetic resonance imaging (rs-fMRI)
      connectivity analysis through more realistic assumptions. In simulation, the
      advantages of such methods are readily demonstrable. However, quantitative
      empirical validation remains elusive in vivo as the true connectivity patterns
      are unknown and noise distributions are challenging to characterize, especially
      in ultra-high field (e.g., 7T fMRI). Though the physiological characteristics of
      the fMRI signal are difficult to replicate in controlled phantom studies, it is
      critical that the performance of statistical techniques be evaluated. The
      SIMulation EXtrapolation (SIMEX) method has enabled estimation of bias with
      asymptotically consistent estimators on empirical finite sample data by adding
      simulated noise . To avoid the requirement of accurate estimation of noise
      structure, the proposed quantitative evaluation approach leverages the
      theoretical core of SIMEX to study the properties of inference methods in the
      face of diminishing data (in contrast to increasing noise). The performance of
      ordinary and robust inference methods in simulation and empirical rs-fMRI are
      compared using the proposed quantitative evaluation approach. This study provides
      a simple, but powerful method for comparing a proxy for inference accuracy using
      empirical data. 

PMID- 24658236
TI  - Compressed sensing dynamic cardiac cine MRI using learned spatiotemporal
      dictionary.
AB  - In dynamic cardiac cine magnetic resonance imaging, the spatiotemporal resolution
      is limited by the low imaging speed. Compressed sensing (CS) theory has been
      applied to improve the imaging speed and thus the spatiotemporal resolution. In
      this paper, we propose a novel technique that employs a patch-based 3-D
      spatiotemporal dictionary for sparse representations of dynamic image sequence in
      the CS framework. Specifically, the dynamic image sequence is divided into
      overlapping patches along both the spatial and temporal directions. The
      dictionary is used to provide flexible sparse expressions for these patches. The
      underlying optimization problem is solved by variable splitting and the
      alternating direction method with multiplier. Experimental results based on in
      vivo cardiac data demonstrate that the proposed method is able to accelerate
      cardiac cine imaging by a factor up to 8 and outperforms the existing state-of
      the-art CS methods at high accelerations. The method is expected to be useful in
      dynamic imaging with a higher spatiotemporal resolution. 

PMID- 24658237
TI  - Automatic segmentation of a fetal echocardiogram using modified active appearance
      models and sparse representation.
AB  - A novel approach is presented to automatically segment the left ventricle in
      fetal echocardiograms. The proposed approach strategically integrates sparse
      representation, global constraint, and local refinement algorithms into an active
      appearance model (AAM) framework. In the training stage, we construct an enhanced
      AAM texture model to deal with the speckle and texture ambiguities. In the
      segmentation stage, the initial pose is located by a sparse representation
      method. Globally constrained points and local features with high clinical
      relevance are effectively incorporated into the AAM framework to make the model
      converge toward a desired position. Our proposed approach has been compared with
      the traditional ASM, the traditional AAM, and the globally constrained AAM on the
      synthetic and clinical data. The results show that compared with experts drawn
      contours, the overall segmentation accuracy of overlapped area in the synthetic
      and clinical images are 84.12% and 84.39%, respectively, superior to those of the
      other three methods. The experiments demonstrate that sparse representative
      methods greatly facilitate the initializations and our approach is capable of
      detecting the fetal left ventricle effectively, offering a better segmentation
      results. 

PMID- 24658238
TI  - Movement stability analysis of surface electromyography-based elbow power
      assistance.
AB  - The use of power assistive devices that use surface electromyography (SEMG)
      signals may be limited by the noisy nature of SEMG signals. The aim of this study
      was to investigate the variation in human movement stability while the amount of
      SEMG-based assistive power was changed. A robotic device provided a torque that
      was proportional to the torque estimated by SEMG for assisting human movements,
      and 12 volunteers participated in the elbow flexion experiments. The maximum
      finite-time Lyapunov exponent (MFTLE), the average logarithmic rate of the
      divergence of neighboring trajectories, and the variability of the kinematic data
      were used to quantify the stability of the assisted elbow movements. The
      stability provided by the MFTLE decreased as the amount of assistive torque
      increased with respect to the amount of human torque. The kinematic variability
      increased with the increase in assistive torque. Therefore, by ensuring that the
      amount of SEMG-based assistive torque is less than the amount of human torque,
      the assistance may provide relatively natural movements. This study is the first
      to quantify movement stability as SEMG-based assistive power is applied. This
      study can provide a foundation for determining the appropriate amount of SEMG
      based assistive power. 

PMID- 24658239
TI  - Glaucoma progression detection using structural retinal nerve fiber layer
      measurements and functional visual field points.
AB  - Machine learning classifiers were employed to detect glaucomatous progression
      using longitudinal series of structural data extracted from retinal nerve fiber
      layer thickness measurements and visual functional data recorded from standard
      automated perimetry tests. Using the collected data, a longitudinal feature
      vector was created for each patient's eye by computing the norm 1 difference
      vector of the data at the baseline and at each follow-up visit. The longitudinal
      features from each patient's eye were then fed to the machine learning classifier
      to classify each eye as stable or progressed over time. This study was performed
      using several machine learning classifiers including Bayesian, Lazy, Meta, and
      Tree, composing different families. Combinations of structural and functional
      features were selected and ranked to determine the relative effectiveness of each
      feature. Finally, the outcomes of the classifiers were assessed by several
      performance metrics and the effectiveness of structural and functional features
      were analyzed. 

PMID- 24658240
TI  - Lung nodule classification with multilevel patch-based context analysis.
AB  - In this paper, we propose a novel classification method for the four types of
      lung nodules, i.e., well-circumscribed, vascularized, juxta-pleural, and pleural
      tail, in low dose computed tomography scans. The proposed method is based on
      contextual analysis by combining the lung nodule and surrounding anatomical
      structures, and has three main stages: an adaptive patch-based division is used
      to construct concentric multilevel partition; then, a new feature set is designed
      to incorporate intensity, texture, and gradient information for image patch
      feature description, and then a contextual latent semantic analysis-based
      classifier is designed to calculate the probabilistic estimations for the
      relevant images. Our proposed method was evaluated on a publicly available
      dataset and clearly demonstrated promising classification performance. 

PMID- 24658241
TI  - Self-correcting pattern recognition system of surface EMG signals for upper limb
      prosthesis control.
AB  - Pattern recognition methods for classifying user motion intent based on surface
      electromyography developed by research groups in well-controlled laboratory
      conditions are not yet clinically viable for upper limb prosthesis control, due
      to their limited robustness in users' real-life situations. To address this
      problem, a novel postprocessing algorithm, aiming to detect and remove
      misclassifications of a pattern recognition system of forearm and hand motions,
      is proposed. Using the maximum likelihood calculated by a classifier and the mean
      global muscle activity of the forearm, an artificial neural network was trained
      to detect potentially erroneous classification decisions. This system was
      compared to four previously proposed classification postprocessing methods, in
      both able-bodied and amputee subjects. Various nonstationarities were included in
      the experimental protocol to account for challenges posed in real-life settings,
      such as different contraction levels, static and dynamic motion phases, and
      effects induced by day-to-day transfers, such as electrode shifts, impedance
      changes, and psychometric user variability. The improvement in classification
      accuracy with respect to the unprocessed classifier ranged from 4.8% to 31.6%,
      depending on the scenarios investigated. The system significantly reduced
      misclassifications to wrong active classes and is thus a promising approach for
      improving the robustness of hand prosthesis controllability. 

PMID- 24658242
TI  - Measurement of forces at the tip of a cochlear implant during insertion.
AB  - An optical fiber-based sensor has been developed to measure the forces at the tip
      of an electrode array during insertion into the cochlea. The sensor, utilizing
      optical fiber Bragg grating technology, was incorporated into a custom-designed
      Pt-banded electrode array for guinea pigs. In vivo experiments were undertaken in
      which forces at the tip of the array were measured in real time during the
      insertion. Data were obtained for maximum insertion forces of up to 254 mN.
      Histology was performed on the excised cochleae with the sensors fixed in
      position to evaluate the level of insertion trauma. The insertion experiments
      demonstrated a clear correlation between the applied force and collateral tissue
      damage. 

PMID- 24658243
TI  - A new dimensionless index for evaluating cell stiffness-based deformability in
      microchannel.
AB  - This paper proposes a new index for evaluating the stiffness-based deformability
      of a cell using a microchannel. In conventional approaches, the transit time of a
      cell through a microchannel is often utilized for the evaluation of cell
      deformability. However, such time includes both the information of cell stiffness
      and viscosity. In this paper, we eliminate the effect from cell viscosity, and
      focus on the cell stiffness only. We find that the velocity of a cell varies when
      it enters a channel, and eventually reaches to equilibrium where the velocity
      becomes constant. The constant velocity is defined as the equilibrium velocity of
      the cell, and it is utilized to define the observability of stiffness-based
      deformability. The necessary and sufficient numbers of sensing points for
      evaluating stiffness-based deformability are discussed. Through the dimensional
      analysis on the microchannel system, three dimensionless parameters determining
      stiffness-based deformability are derived, and a new index is introduced based on
      these parameters. The experimental study is conducted on the red blood cells from
      a healthy subject and a diabetes patient. With the proposed index, we showed that
      the experimental data can be nicely arranged. 

PMID- 24658244
TI  - Noninvasive subject-specific monitoring of autonomic-cardiac regulation.
AB  - This paper presents a feasibility study of a model-based approach to noninvasive
      and subject-specific monitoring of autonomic-cardiac regulation. The proposed
      approach is built upon individualizing a physiologically-based model by applying
      a parameter estimation method to routine clinical observations, thereby assuring
      physical transparency, computational efficiency, and clinical adaptability. To
      develop an efficient parameter estimation procedure, a parametric sensitivity
      analysis was performed on the autonomic-cardiac regulation model to identify high
      sensitivity model parameters whose changes exert significant impacts on the
      system outputs. Then, a parameter estimation problem formulated as a nonlinear
      optimization was solved to estimate high-sensitivity model parameters associated
      with autonomic-cardiac regulation, whereas the remaining parameters were fixed at
      their nominal values. The proposed approach can potentially monitor temporal
      changes in autonomic-cardiac regulation by identifying time-varying changes in
      the autonomic-cardiac model parameters, including sympathetic and parasympathetic
      nerve activities on the heart (modulating heart rate), and sympathetic nerve
      activity on the arterial tree (modulating total peripheral resistance). The proof
      of-concept for the proposed approach was tested using a number of experimental
      data from the MIMIC database and the orthostatic hypotension tests. Our finding
      shows that the proposed approach is able to provide low-variance estimates of the
      autonomic-cardiac model parameters, which are consistent with their anticipated
      behaviors inferred from the physiologic knowledge. An extensive comparison study
      must be conducted in the future to establish the clinical validity of the
      proposed approach. 

PMID- 24658245
TI  - Sensitivity analysis and parameter estimation of a coronary circulation model for
      triple-vessel disease.
AB  - Mathematical models of the coronary circulation have been shown to provide useful
      information for the analysis of intracoronary blood flow and pressure
      measurements acquired during coronary artery bypass graft (CABG) surgery.
      Although some efforts towards the patient-specific estimation of model parameters
      have been presented in this context, they are based on simplifying hypotheses
      about the collateral circulation and do not take advantage of the whole set of
      data acquired during CABG. In order to overcome these limitations, this paper
      presents an exhaustive parameter sensitivity analysis and a multiobjective
      patient-specific parameter estimation method, applied to a model of the coronary
      circulation of patients with triple vessel disease. The results of the
      sensitivity analysis highlighted the importance of capillary and collateral
      development. On the other hand, the estimation method was applied to
      intraoperative clinical data from ten patients obtained during CABG, which
      permitted to assess patient-specific collateral vessel situations. These
      approaches provide new insights regarding the heterogeneous configuration of the
      collateral circulation. 

PMID- 24658246
TI  - Segmentation of skin lesions from digital images using joint statistical texture
      distinctiveness.
AB  - Melanoma is the deadliest form of skin cancer. Incidence rates of melanoma have
      been increasing, especially among non-Hispanic white males and females, but
      survival rates are high if detected early. Due to the costs for dermatologists to
      screen every patient, there is a need for an automated system to assess a
      patient's risk of melanoma using images of their skin lesions captured using a
      standard digital camera. One challenge in implementing such a system is locating
      the skin lesion in the digital image. A novel texture-based skin lesion
      segmentation algorithm is proposed. A set of representative texture distributions
      are learned from an illumination-corrected photograph and a texture
      distinctiveness metric is calculated for each distribution. Next, regions in the
      image are classified as normal skin or lesion based on the occurrence of
      representative texture distributions. The proposed segmentation framework is
      tested by comparing lesion segmentation results and melanoma classification
      results to results using other state-of-art algorithms. The proposed framework
      has higher segmentation accuracy compared to all other tested algorithms. 

PMID- 24658247
TI  - Modeling biology with HDL languages: a first step toward a genetic design
      automation tool inspired from microelectronics.
AB  - Nowadays, synthetic biology is a hot research topic. Each day, progresses are
      made to improve the complexity of artificial biological functions in order to
      tend to complex biodevices and biosystems. Up to now, these systems are handmade
      by bioengineers, which require strong technical skills and leads to nonreusable
      development. Besides, scientific fields that share the same design approach, such
      as microelectronics, have already overcome several issues and designers succeed
      in building extremely complex systems with many evolved functions. On the other
      hand, in systems engineering and more specifically in microelectronics, the
      development of the domain has been promoted by both the improvement of
      technological processes and electronic design automation tools. The work
      presented in this paper paves the way for the adaptation of microelectronics
      design tools to synthetic biology. Considering the similarities and differences
      between the synthetic biology and microelectronics, the milestones of this
      adaptation are described. The first one concerns the modeling of biological
      mechanisms. To do so, a new formalism is proposed, based on an extension of the
      generalized Kirchhoff laws to biology. This way, a description of all biological
      mechanisms can be made with languages widely used in microelectronics. Our
      approach is therefore successfully validated on specific examples drawn from the
      literature. 

PMID- 24658249
TI  - Direct estimation of cardiac biventricular volumes with an adapted Bayesian
      formulation.
AB  - Accurate estimation of the ventricular volumes is essential to the assessment of
      global cardiac functions. The existing estimation methods are mostly restricted
      to the left ventricle (LV), and often require segmentation which is challenging
      and computationally expensive. This paper proposes to estimate the volumes of
      both LV and right ventricle (RV) jointly with an efficient segmentation-free
      method. The proposed method employs an adapted Bayesian formulation. It
      introduces a novel likelihood function to exploit multiple appearance features,
      and a novel prior probability model to incorporate the area correlation between
      LV and RV cavities. The method is validated on a comprehensive dataset containing
      56 clinical subjects (3360 images in total). The experimental results demonstrate
      that the estimated biventricular volumes are highly correlated to their
      independent ground truth. As a result, the proposed method enables a direct,
      efficient, and accurate assessment of global cardiac functions. 

PMID- 24658248
TI  - Joint spatial-spectral feature space clustering for speech activity detection
      from ECoG signals.
AB  - Brain-machine interfaces for speech restoration have been extensively studied for
      more than two decades. The success of such a system will depend in part on
      selecting the best brain recording sites and signal features corresponding to
      speech production. The purpose of this study was to detect speech activity
      automatically from electrocorticographic signals based on joint spatial-frequency
      clustering of the ECoG feature space. For this study, the ECoG signals were
      recorded while a subject performed two different syllable repetition tasks. We
      found that the optimal frequency resolution to detect speech activity from ECoG
      signals was 8 Hz, achieving 98.8% accuracy by employing support vector machines
      as a classifier. We also defined the cortical areas that held the most
      information about the discrimination of speech and nonspeech time intervals.
      Additionally, the results shed light on the distinct cortical areas associated
      with the two syllables repetition tasks and may contribute to the development of
      portable ECoG-based communication. 

PMID- 24658250
TI  - Gait parameter estimation from a miniaturized ear-worn sensor using singular
      spectrum analysis and longest common subsequence.
AB  - This paper presents a new approach to gait analysis and parameter estimation from
      a single miniaturized ear-worn sensor embedded with a triaxial accelerometer.
      Singular spectrum analysis combined with the longest common subsequence algorithm
      has been used as a basis for gait parameter estimation. It incorporates
      information from all axes of the accelerometer to estimate parameters including
      swing, stance, and stride times. Rather than only using local features of the raw
      signals, the periodicity of the signals is also taken into account. The
      hypotheses tested by this study include: 1) how accurate is the ear-worn sensor
      in terms of gait parameter extraction compared to the use of an instrumented
      treadmill; 2) does the ear-worn sensor provide a feasible option for assessment
      and quantification of gait pattern changes. Key gait events for normal subjects
      such as heel contact and toe off are validated with a high-speed camera, as well
      as a force-plate instrumented treadmill. Ten healthy adults walked for 20 min on
      a treadmill with an increasing incline of 2% every 2 min. The upper and lower
      limits of the absolute errors using 95% confidence intervals for swing, stance,
      and stride times were obtained as 35.5 +/-3.99 ms, 36.9 +/-3.84 ms, and 17.9 +/
      2.29 ms, respectively. 

PMID- 24658251
TI  - Bimodal BCI using simultaneously NIRS and EEG.
AB  - Although noninvasive brain-computer interfaces (BCI) based on
      electroencephalographic (EEG) signals have been studied increasingly over the
      recent decades, their performance is still limited in two important aspects.
      First, the difficulty of performing a reliable detection of BCI commands
      increases when EEG epoch length decreases, which makes high information transfer
      rates difficult to achieve. Second, the BCI system often misclassifies the EEG
      signals as commands, although the subject is not performing any task. In order to
      circumvent these limitations, the hemodynamic fluctuations in the brain during
      stimulation with steady-state visual evoked potentials (SSVEP) were measured
      using near-infrared spectroscopy (NIRS) simultaneously with EEG. BCI commands
      were estimated based on responses to a flickering checkerboard (ON-period).
      Furthermore, an "idle" command was generated from the signal recorded by the NIRS
      system when the checkerboard was not flickering (OFF-period). The joint use of
      EEG and NIRS was shown to improve the SSVEP classification. For 13 subjects, the
      relative improvement in error rates obtained by using the NIRS signal, for nine
      classes including the "idle" mode, ranged from 85% to 53 %, when the epoch length
      increase from 3 to 12 s. These results were obtained from only one EEG and one
      NIRS channel. The proposed bimodal NIRS-EEG approach, including detection of the
      idle mode, may make current BCI systems faster and more reliable. 

PMID- 24658252
TI  - Three-dimensional transcranial ultrasound imaging of microbubble clouds using a
      sparse hemispherical array.
AB  - There is an increasing interest in bubble-mediated focused ultrasound (FUS)
      interventions in the brain. However, current technology lacks the ability to
      spatially monitor the interaction of the microbubbles with the applied acoustic
      field, something which is critical for safe clinical translation of these
      treatments. Passive acoustic mapping could offer a means for spatially monitoring
      microbubble emissions that relate to bubble activity and associated bioeffects.
      In this study, a hemispherical receiver array was integrated within an existing
      transcranial therapy array to create a device capable of both delivering therapy
      and monitoring the process via passive imaging of bubble clouds. A 128-element
      receiver array was constructed and characterized for varying bubble
      concentrations and source spacings. Initial in vivo feasibility testing was
      performed. The system was found to be capable of monitoring bubble emissions down
      to single bubble events through an ex vivo human skull. The lateral resolution of
      the system was found to be between 1.25 and 2 mm and the axial resolution between
      2 and 3.5 mm, comparable to the resolution of MRI-based temperature monitoring
      during thermal FUS treatments in the brain. The results of initial in vivo
      experiments show that bubble activity can be mapped starting at pressure levels
      below the threshold for blood-brain barrier disruption. This study presents a
      feasible solution for imaging bubble activity during cavitation-mediated FUS
      treatments in the brain. 

PMID- 24658253
TI  - Augmented reality navigation with automatic marker-free image registration using
      3-D image overlay for dental surgery.
AB  - Computer-assisted oral and maxillofacial surgery (OMS) has been rapidly evolving
      since the last decade. State-of-the-art surgical navigation in OMS still suffers
      from bulky tracking sensors, troublesome image registration procedures, patient
      movement, loss of depth perception in visual guidance, and low navigation
      accuracy. We present an augmented reality navigation system with automatic marker
      free image registration using 3-D image overlay and stereo tracking for dental
      surgery. A customized stereo camera is designed to track both the patient and
      instrument. Image registration is performed by patient tracking and real-time 3-D
      contour matching, without requiring any fiducial and reference markers. Real-time
      autostereoscopic 3-D imaging is implemented with the help of a consumer-level
      graphics processing unit. The resulting 3-D image of the patient's anatomy is
      overlaid on the surgical site by a half-silvered mirror using image registration
      and IP-camera registration to guide the surgeon by exposing hidden critical
      structures. The 3-D image of the surgical instrument is also overlaid over the
      real one for an augmented display. The 3-D images present both stereo and motion
      parallax from which depth perception can be obtained. Experiments were performed
      to evaluate various aspects of the system; the overall image overlay error of the
      proposed system was 0.71 mm. 

PMID- 24658254
TI  - Smart tissue anastomosis robot (STAR): a vision-guided robotics system for
      laparoscopic suturing.
AB  - This paper introduces the smart tissue anastomosis robot (STAR). Currently, the
      STAR is a proof-of-concept for a vision-guided robotic system featuring an
      actuated laparoscopic suturing tool capable of executing running sutures from
      image-based commands. The STAR tool is designed around a commercially available
      laparoscopic suturing tool that is attached to a custom-made motor stage and the
      STAR supervisory control architecture that enables a surgeon to select and track
      incisions and the placement of stitches. The STAR supervisory-control interface
      provides two modes: A manual mode that enables a surgeon to specify the placement
      of each stitch and an automatic mode that automatically computes equally-spaced
      stitches based on an incision contour. Our experiments on planar phantoms
      demonstrate that the STAR in either mode is more accurate, up to four times more
      consistent and five times faster than surgeons using state-of-the-art robotic
      surgical system, four times faster than surgeons using manual Endo360( degrees
      )(r), and nine times faster than surgeons using manual laparoscopic tools.

PMID- 24658255
TI  - Sensory subtraction in robot-assisted surgery: fingertip skin deformation
      feedback to ensure safety and improve transparency in bimanual haptic
      interaction.
AB  - This study presents a novel approach to force feedback in robot-assisted surgery.
      It consists of substituting haptic stimuli, composed of a kinesthetic component
      and a skin deformation, with cutaneous stimuli only. The force generated can then
      be thought as a subtraction between the complete haptic interaction, cutaneous,
      and kinesthetic, and the kinesthetic part of it. For this reason, we refer to
      this approach as sensory subtraction. Sensory subtraction aims at outperforming
      other nonkinesthetic feedback techniques in teleoperation (e.g., sensory
      substitution) while guaranteeing the stability and safety of the system. We
      tested the proposed approach in a challenging 7-DoF bimanual teleoperation task,
      similar to the Pegboard experiment of the da Vinci Skills Simulator. Sensory
      subtraction showed improved performance in terms of completion time, force
      exerted, and total displacement of the rings with respect to two popular sensory
      substitution techniques. Moreover, it guaranteed a stable interaction in the
      presence of a communication delay in the haptic loop. 

PMID- 24658256
TI  - Nonparametric signal processing validation in T-wave alternans detection and
      estimation.
AB  - Although a number of methods have been proposed for T-Wave Alternans (TWA)
      detection and estimation, their performance strongly depends on their signal
      processing stages and on their free parameters tuning. The dependence of the
      system quality with respect to the main signal processing stages in TWA
      algorithms has not yet been studied. This study seeks to optimize the final
      performance of the system by successive comparisons of pairs of TWA analysis
      systems, with one single processing difference between them. For this purpose, a
      set of decision statistics are proposed to evaluate the performance, and a
      nonparametric hypothesis test (from Bootstrap resampling) is used to make
      systematic decisions. Both the temporal method (TM) and the spectral method (SM)
      are analyzed in this study. The experiments were carried out in two datasets:
      first, in semisynthetic signals with artificial alternant waves and added noise;
      second, in two public Holter databases with different documented risk of sudden
      cardiac death. For semisynthetic signals (SNR = 15 dB), after the optimization
      procedure, a reduction of 34.0% (TM) and 5.2% (SM) of the power of TWA amplitude
      estimation errors was achieved, and the power of error probability was reduced by
      74.7% (SM). For Holter databases, appropriate tuning of several processing
      blocks, led to a larger intergroup separation between the two populations for TWA
      amplitude estimation. Our proposal can be used as a systematic procedure for
      signal processing block optimization in TWA algorithmic implementations. 

PMID- 24658257
TI  - Techniques to improve the accuracy of presampling MTF measurement in digital X
      ray imaging based on constrained spline regression.
AB  - To develop an effective curve-fitting algorithm with a regularization term for
      measuring the modulation transfer function (MTF) of digital radiographic imaging
      systems, in comparison with representative prior methods, a C-spline regression
      technique based upon the monotonicity and convex/concave shape restrictions of
      the edge spread function (ESF) was proposed for ESF estimation in this study. Two
      types of oversampling techniques and following four curve-fitting algorithms
      including the C-spline regression technique were considered for ESF estimation. A
      simulated edge image with a known MTF was used for accuracy determination of
      algorithms. Experimental edge images from two digital radiography systems were
      used for statistical evaluation of each curve-fitting algorithm on MTF
      measurements uncertainties. The simulation results show that the C-spline
      regression algorithm obtained a minimum MTF measurement error (an average error
      of 0.12% +/- 0.11% and 0.18% +/- 0.17% corresponding to two types of oversampling
      techniques, respectively, up to the cutoff frequency) among all curve-fitting
      algorithms. In the case of experimental edge images, the C-spline regression
      algorithm obtained the best uncertainty performance of MTF measurement among four
      curve-fitting algorithms for both the Pixarray-100 digital specimen radiography
      system and Hologic full-field digital mammography system. Comparisons among MTF
      estimates using four curve-fitting algorithms revealed that the proposed C-spline
      regression technique outperformed other algorithms on MTF measurements accuracy
      and uncertainty performance. 

PMID- 24658258
TI  - Design and experimental evaluation of a 256-channel dual-frequency ultrasound
      phased-array system for transcranial blood-brain barrier opening and brain drug
      delivery.
AB  - Focused ultrasound (FUS) in the presence of microbubbles can bring about
      transcranial and local opening of the blood-brain barrier (BBB) for potential
      noninvasive delivery of drugs to the brain. A phased-array ultrasound system is
      essential for FUS-BBB opening to enable electronic steering and correction of the
      focal beam which is distorted by cranial bone. Here, we demonstrate our prototype
      design of a 256-channel ultrasound phased-array system for large-region
      transcranial BBB opening in the brains of large animals. One of the unique
      features of this system is the capability of generating concurrent dual-frequency
      ultrasound signals from the driving system for potential enhancement of BBB
      opening. A wide range of signal frequencies can be generated (frequency = 0.2-1.2
      MHz) with controllable driving burst patterns. Precise output power can be
      controlled for individual channels via 8-bit duty-cycle control of transistor
      transistor logic signals and the 8-bit microcontroller-controlled buck converter
      power supply output voltage. The prototype system was found to be in compliance
      with the electromagnetic compatibility standard. Moreover, large animal
      experiments confirmed the phase switching effectiveness of this system, and
      induction of either a precise spot or large region of BBB opening through fast
      focal-beam switching. We also demonstrated the capability of dual-frequency
      exposure to potentially enhance the BBB-opening effect. This study contributes to
      the design of ultrasound phased arrays for future clinical applications, and
      provides a new direction toward optimizing FUS brain drug delivery. 

PMID- 24658259
TI  - Diel nitrogen fixation pattern of Trichodesmium: the interactive control of light
      and Ni.
AB  - Trichodesmium, a nonheterocystous cyanobacterium widely abundant in the surface
      water of the tropical and subtropical ocean, fixes dinitrogen under high light
      conditions while concurrently undergoing photosynthesis. The new production
      considerably influences the cycling of nitrogen and carbon in the ocean. Here, we
      investigated how light intensity and nickel (Ni) availability interplay to
      control daily rates and diel patterns of N2 fixation in Trichodesmium. We found
      that increasing Ni concentration increased N2 fixation rates by up to 30-fold in
      the high light treatment. Cultures subjected to high Ni and light levels fixed
      nitrogen throughout most of the 24 H light:dark regime with the highest rate
      coinciding with the end of the 12 H light period. Our study demonstrates the
      importance of Ni on nitrogen fixation rates for Trichodesmium under high light
      conditions. 

PMID- 24658260
TI  - A structurally-characterized NbCl5-NHC adduct.
AB  - The selective reactions of niobium pentachloride with two bulky NHC carbenes
      afforded NbCl5(NHC) complexes, bearing the highest oxidation state ever found for
      a metal centre in a transition metal halide-NHC adduct. The X-ray structure of 2a
      is the first one reported for a monodentate NHC-niobium species, and exhibits an
      abnormally long Nb-C bond. 

PMID- 24658261
TI  - Using natural selection to explore the adaptive potential of Chlamydomonas
      reinhardtii.
AB  - Improving feedstock is critical to facilitate the commercial utilization of
      algae, in particular in open pond systems where, due to the presence of
      competitors and pests, high algal growth rates and stress tolerance are
      beneficial. Here we raised laboratory cultures of the model alga Chlamydomonas
      reinhardtii under serial dilution to explore the potential of crop improvement
      using natural selection. The alga was evolved for 1,880 generations in liquid
      medium under continuous light (EL population). At the end of the experiment, EL
      cells had a growth rate that was 35% greater than the progenitor population (PL).
      The removal of acetate from the medium demonstrated that EL growth enhancement
      largely relied on efficient usage of this organic carbon source. Genome re
      sequencing uncovered 1,937 polymorphic DNA regions in the EL population with 149
      single nucleotide polymorphisms resulting in amino acid substitutions.
      Transcriptome analysis showed, in the EL population, significant up regulation of
      genes involved in protein synthesis, the cell cycle and cellular respiration,
      whereas the DNA repair pathway and photosynthesis were down regulated. Like other
      algae, EL cells accumulated neutral lipids under nitrogen depletion. Our work
      demonstrates transcriptome and genome-wide impacts of natural selection on algal
      cells and points to a useful strategy for strain improvement. 

PMID- 24658262
TI  - Behavioural effects of the commonly used fish anaesthetic tricaine
      methanesulfonate (MS-222) on zebrafish (Danio rerio) and its relevance for the
      acetic acid pain test.
AB  - The pros and cons of using anaesthesia when handling fish in connection with
      experiments are debated. A widely adopted practice is to wait thirty minutes
      after anaesthesia before behavioural observations are initiated, but information
      about immediate effects of a treatment is then lost. This is pertinent for
      responses to acute stressors, such as acid injection in the acetic acid pain
      test. However, omission of anaesthetics in order to obtain data on immediate
      responses will compromise the welfare of fish and contribute to experimental
      noise due to stress. We therefore tested the effect of tricaine methanesulfonate
      on the behaviour of zebrafish. We predicted that tricaine (MS 222) would decrease
      swimming velocity and that the control fish would show an increased level of
      anxiety- and stress-related behaviours compared to the tricaine group. Following
      acclimatization to the test tank, baseline behaviour was recorded before
      immersion in either tricaine (168 mg l(-1), treatment group, N = 8) or tank water
      (control group, N = 7). Latencies to lose equilibrium and to lose response to
      touch were registered. The fish was then returned to the test tank, and the
      latency to regain equilibrium was registered in anaesthetized fish. When
      equilibrium was regained, and at five, thirty and sixty minutes after the fish
      had been returned to the test tank, behaviour was recorded. The tricaine fish
      showed the following responses (mean +/- sd): latency to lose equilibrium 22.6
      s+/-3.9; latency to lose response to touch 101.9 s+/-26.8; latency to regain
      equilibrium 92.0 s+/-54.4. Contrary to our predictions, neither treatment caused
      a change in any of the behaviours registered. This indicates that tricaine has no
      effect on several commonly used behavioural parameters, and that it may be
      unnecessary to postpone behavioural observations to 30 min after anaesthesia.

PMID- 24658264
TI  - Synthesis of CVD-graphene on rapidly heated copper foils.
AB  - Most chemical vapor deposition (CVD) systems used for graphene growth mainly
      employ convection and radiation heat transfer between the heating source and the
      metal catalyst in order to reach the activation temperature of the reaction,
      which in general leads to a long synthesis time and poor energy efficiency. Here,
      we report a highly time- and energy-efficient CVD setup, in which the metal
      catalyst (Cu) is designed to be physically contacted with a heating source to
      give quick heat transfer by conduction. The induced conduction heating enabled
      the usual effects of the pretreatment and annealing of Cu (i.e., annihilation of
      surface defects, impurities and contaminants) to be achieved in a significantly
      shorter time compared to conventional CVD. Notably, the rapid heating was
      observed to lead to larger grains of Cu with high uniformity as compared to the
      Cu annealed by conventional CVD, which are believed to be beneficial for the
      growth of high quality graphene. Through this CVD setup, bundles of high quality
      (~252 Omega per square) and large area (over 16 inch) graphenes were able to be
      readily synthesized in 40 min in a significantly efficient way. When considering
      ease of scalability, high energy effectiveness and considerable productivity, our
      method is expected to be welcomed by industrialists. 

PMID- 24658263
TI  - Inhibiting spinal neuron-astrocytic activation correlates with synergistic
      analgesia of dexmedetomidine and ropivacaine.
AB  - BACKGROUND: This study aims to identify that intrathecal (i.t.) injection of
      dexmedetomidine (Dex) and ropivacaine (Ropi) induces synergistic analgesia on
      chronic inflammatory pain and is accompanied with corresponding "neuron
      astrocytic" alterations. METHODS: Male, adult Sprague-Dawley rats were randomly
      divided into sham, control and i.t. medication groups. The analgesia profiles of
      i.t. Dex, Ropi, and their combination detected by Hargreaves heat test were
      investigated on the subcutaneous (s.c.) injection of complete Freund adjuvant
      (CFA) induced chronic pain in rat and their synergistic analgesia was confirmed
      by using isobolographic analysis. During consecutive daily administration, pain
      behavior was daily recorded, and immunohistochemical staining was applied to
      investigate the number of Fos-immunoreactive (Fos-ir) neurons on hour 2 and day
      1, 3 and 7, and the expression of glial fibrillary acidic protein (GFAP) within
      the spinal dorsal horn (SDH) on day 1, 3, 5 and 7 after s.c. injection of CFA,
      respectively, and then Western blot to examine spinal GFAP and beta-actin levels
      on day 3 and 7. RESULTS: i.t. Dex or Ropi displayed a short-term analgesia in a
      dose-dependent manner, and consecutive daily administrations of their combination
      showed synergistic analgesia and remarkably down-regulated neuronal and
      astrocytic activations indicated by decreases in the number of Fos-ir neurons and
      the GFAP expression within the SDH, respectively. CONCLUSION: i.t. co-delivery of
      Dex and Ropi shows synergistic analgesia on the chronic inflammatory pain, in
      which spinal "neuron-astrocytic activation" mechanism may play an important role.

PMID- 24658265
TI  - Tumour microenvironment: more than just a mutagen.

PMID- 24658270
TI  - Pluripotency: partial reprogramming induces cancer.

PMID- 24658271
TI  - Tumour suppressors: Hippo promotes microRNA processing.

PMID- 24658277
TI  - The sizing of hamstring grafts for anterior cruciate reconstruction: intra- and
      inter-observer reliability.
AB  - PURPOSE: The objective of this study was to establish the intra- and inter
      observer reliability of hamstring graft measurement using cylindrical sizing
      tubes. METHODS: Hamstring tendons (gracilis and semitendinosus) were harvested
      from ten cadavers by a single surgeon and whip stitched together to create ten 4
      strand hamstring grafts. Ten sports medicine surgeons and fellows sized each
      graft independently using either hollow cylindrical sizers or block sizers in 0.5
      mm increments-the sizing technique used was applied consistently to each graft.
      Surgeons moved sequentially from graft to graft and measured each hamstring graft
      twice. Surgeons were asked to state the measured proximal (femoral) and distal
      (tibial) diameter of each graft, as well as the diameter of the tibial and
      femoral tunnels that they would drill if performing an anterior cruciate ligament
      (ACL) reconstruction using that graft. Reliability was established using intra
      class correlation coefficients. RESULTS: Overall, both the inter-observer and
      intra-observer agreement were >0.9, demonstrating excellent reliability. The
      inter-observer reliability for drill sizes was also excellent (>0.9). Excellent
      correlation was seen between cylindrical sizing, and drill sizes (>0.9).
      CONCLUSIONS: Sizing of hamstring grafts by multiple surgeons demonstrated
      excellent intra-observer and intra-observer reliability, potentially validating
      clinical studies exploring ACL reconstruction outcomes by hamstring graft
      diameter when standard techniques are used. LEVEL OF EVIDENCE: III.

PMID- 24658274
TI  - Roles of F-box proteins in cancer.
AB  - F-box proteins, which are the substrate-recognition subunits of SKP1-cullin 1-F
      box protein (SCF) E3 ligase complexes, have pivotal roles in multiple cellular
      processes through ubiquitylation and subsequent degradation of target proteins.
      Dysregulation of F-box protein-mediated proteolysis leads to human malignancies.
      Notably, inhibitors that target F-box proteins have shown promising therapeutic
      potential, urging us to review the current understanding of how F-box proteins
      contribute to tumorigenesis. As the physiological functions for many of the 69
      putative F-box proteins remain elusive, additional genetic and mechanistic
      studies will help to define the role of each F-box protein in tumorigenesis,
      thereby paving the road for the rational design of F-box protein-targeted
      anticancer therapies. 

PMID- 24658273
TI  - Targeting Bruton's tyrosine kinase in B cell malignancies.
AB  - Bruton's tyrosine kinase (BTK) is a key component of B cell receptor (BCR)
      signalling and functions as an important regulator of cell proliferation and cell
      survival in various B cell malignancies. Small-molecule inhibitors of BTK have
      shown antitumour activity in animal models and, recently, in clinical studies.
      High response rates were reported in patients with chronic lymphocytic leukaemia
      and mantle cell lymphoma. Remarkably, BTK inhibitors have molecular effects that
      cannot be explained by the classic role of BTK in BCR signalling. In this Review,
      we highlight the importance of BTK in various signalling pathways in the context
      of its therapeutic inhibition. 

PMID- 24658279
TI  - An induced-fit process through mechanical pivoting of aromatic walls in host
      guest chemistry of calix[6]arene aza-cryptands.
AB  - The per-ipso-nitration of a TMPA-capped calix[6]arene has been achieved. The
      substitution of the six bulky tBu substituents for nitro groups has a strong
      impact on the behavior of the ligand during guest recognition. The complexation
      of the aza cap (by H(+) or Cu(+)) associated with the encapsulation of a guest
      triggers an induced-fit process leading to the loss of the cone conformation of
      the host in favor of alternate conformations. Such a "pivoting" response of one
      or two walls of the calixarene core induces a large mechanical motion of the
      corresponding aromatic units. This stands in strong contrast with the "breathing"
      phenomena previously identified with other calix[6]arene-based complexes that
      expand or shrink the size of their cone as a function of the guest. Because of
      the covalently attached rigid TMPA cap, three arene units of this new calixarene
      host have a restricted mobility, which forces it to respond in a different manner
      to a supramolecular stress. 

PMID- 24658278
TI  - Allopatric diversification, multiple habitat shifts, and hybridization in the
      evolution of Pericallis (Asteraceae), a Macaronesian endemic genus.
AB  - PREMISE OF THE STUDY: Geographic isolation, habitat shifts, and hybridization
      have contributed to the diversification of oceanic island floras. We investigated
      the contribution of these processes to the diversification of Pericallis, a genus
      endemic to Macaronesia. METHODS: Data from the chloroplast psaI-accD and trnV
      ndhC regions and the nuclear ribosomal internal transcribed spacer region (ITS)
      were sampled for multiple accessions of all taxa and used to establish
      phylogenetic hypotheses. Habitat preferences were optimized to investigate
      habitat shifts, and divergence times were estimated. Species nonmonophyly was
      investigated using Bayes factors. KEY RESULTS: Much of the diversification in
      Pericallis has occurred recently, within the past 1.7 Ma. Three habitat shifts
      have occurred in the evolution of the genus. However, geographic isolation has
      played a greater role in its diversification. Novel allopatric patterns were
      revealed within some species, highlighting the significance of geographic
      isolation in the evolution of Pericallis. One species (P. appendiculata) that
      resolved as monophyletic in the ITS analysis was polyphyletic in the chloroplast
      analysis. Bayes factors provide strong support for the nonmonophyly of P.
      appendiculata haplotypes, and their phylogenetic placement suggests that ancient
      hybridization is responsible for the haplotype diversity observed. CONCLUSIONS:
      Multiple markers and extensive sampling provided new insights into the evolution
      of Pericallis. In contrast to previous studies, our results reveal a more
      significant role for allopatry than habitat shifts and new evidence for ancient
      hybridization in the evolution of Pericallis. Our study highlights the power of
      broad taxon sampling for unraveling diversity patterns and processes within
      oceanic island radiations.

PMID- 24658276
TI  - Searching for novel Cdk5 substrates in brain by comparative phosphoproteomics of
      wild type and Cdk5-/- mice.
AB  - Protein phosphorylation is the most common post-translational modification that
      regulates several pivotal functions in cells. Cyclin-dependent kinase 5 (Cdk5) is
      a proline-directed serine/threonine kinase which is mostly active in the nervous
      system. It regulates several biological processes such as neuronal migration,
      cytoskeletal dynamics, axonal guidance and synaptic plasticity among others. In
      search for novel substrates of Cdk5 in the brain we performed quantitative
      phosphoproteomics analysis, isolating phosphoproteins from whole brain derived
      from E18.5 Cdk5+/+ and Cdk5-/- embryos, using an Immobilized Metal-Ion Affinity
      Chromatography (IMAC), which specifically binds to phosphorylated proteins. The
      isolated phosphoproteins were eluted and isotopically labeled for relative and
      absolute quantitation (iTRAQ) and mass spectrometry identification. We found 40
      proteins that showed decreased phosphorylation at Cdk5-/- brains. In addition,
      out of these 40 hypophosphorylated proteins we characterized two proteins,
      :MARCKS (Myristoylated Alanine-Rich protein Kinase C substrate) and Grin1 (G
      protein regulated inducer of neurite outgrowth 1). MARCKS is known to be
      phosphorylated by Cdk5 in chick neural cells while Grin1 has not been reported to
      be phosphorylated by Cdk5. When these proteins were overexpressed in N2A
      neuroblastoma cell line along with p35, serine phosphorylation in their Cdk5
      motifs was found to be increased. In contrast, treatments with roscovitine, the
      Cdk5 inhibitor, resulted in an opposite effect on serine phosphorylation in N2A
      cells and primary hippocampal neurons transfected with MARCKS. In summary, the
      results presented here identify Grin 1 as novel Cdk5 substrate and confirm
      previously identified MARCKS as a a bona fide Cdk5 substrate. 

PMID- 24658275
TI  - Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic
      potential.
AB  - The glucose-regulated proteins (GRPs) are stress-inducible chaperones that mostly
      reside in the endoplasmic reticulum or the mitochondria. Recent advances show
      that the GRPs have functions that are distinct from those of the related heat
      shock proteins, and they can be actively translocated to other cellular locations
      and assume novel functions that control signalling, proliferation, invasion,
      apoptosis, inflammation and immunity. Mouse models further identified their
      specific roles in development, tumorigenesis, metastasis and angiogenesis. This
      Review describes their discovery and regulation, as well as their biological
      functions in cancer. Promising agents that use or target the GRPs are being
      developed, and their efficacy as anticancer therapeutics is also discussed. 

PMID- 24658281
TI  - Collecting meaningful early-time kinetic data in homogeneous catalytic water
      oxidation with a sacrificial oxidant.
AB  - As the field of water oxidation catalysis grows, so does the sophistication of
      the associated experimental apparatuses. However, problems persist in studying
      some of the most basic aspects of catalytic water oxidation including acquisition
      of satisfactory early-reaction-time kinetics and rapid quantification of O2
      concentration. We seek to remedy these problems and through better experimental
      design, elucidate mechanistic aspects of catalytic water oxidation with theory
      backed by experimental data. Two new methods for evaluating homogeneous water
      oxidation catalysts by reaction with a stoichiometric oxidant are presented which
      eliminate problems of incomplete fast mixing and O2 measurement response time.
      These methods generate early-reaction-time kinetics that have previously been
      unavailable. 

PMID- 24658280
TI  - HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and
      invasiveness via PDGFR-alpha activation.
AB  - Our laboratory first demonstrated that human cytomegalovirus (HCMV) is associated
      with the most deadly form of primary brain tumor, glioblastoma (GBM). We showed
      that HCMV glycoprotein B (gB) mediates viral cellular entry via the receptor
      tyrosine kinase PDGFR-alpha (PDGFRalpha), resulting in activation of the PI3K/Akt
      pathway, a critical signaling axis gliomagenesis. Here, we investigated the
      effects of gB overexpression on glioma progression. We demonstrate that gB is
      endogenously expressed in primary GBM samples and show that ectopic gB expression
      in glioma cells induced sustained phosphorylation of PDGFRalpha, Akt, and Src.
      Recombinant gB protein and the whole virus enhanced invasion of primary
      glioblastoma cells into Matrigel and rat brain slices, and this effect was
      specifically inhibited by neutralizing antibodies to either gB or PDGFRalpha.
      Importantly, neutralizing antibodies to gB significantly inhibited the
      invasiveness of patient-derived HCMV-positive glioblastoma cells, suggesting that
      functional inhibition of this viral protein could hinder glioblastoma
      progression. gB overexpression promoted in vivo glioma growth and enhanced
      phosphor-Akt levels and tumor cell dispersal relative to controls. Taken
      together, our results demonstrate that HCMV gB promotes key hallmarks of
      glioblastoma and suggest that targeting gB may have therapeutic benefits for
      patients with HCMV-positive gliomas.

PMID- 24658282
TI  - Motor excitability changes during action observation in stroke patients.
AB  - OBJECTIVE: To explore whether stroke patients exhibit increases in motor
      excitability during action observation, whether differences exist between the
      affected and non-affected sides, and between pure motor strokes and predominantly
      sensory strokes. METHODS: In 18 patients (10 pure motor strokes, 8 predominantly
      sensory strokes, < 6 months after the stroke) transcranial magnetic stimulation
      was used to test motor excitability while the patients viewed a video showing a
      hand performing pinch grips. Transcranial magnetic stimulation pulses were
      applied at 120% of the individual motor threshold at rest, as obtained from the
      affected hemisphere. Recordings were taken simultaneously from the first dorsal
      interosseous muscle of both hands. Motor performance was evaluated with the Box
      and Block Test. RESULTS: Transcranial magnetic stimulation-evoked muscle
      responses obtained from the affected and the unaffected sides were significantly
      higher during action observation than during rest (p = 0.024 and p = 0.004,
      respectively). This effect was significantly stronger when measuring the same
      hand as the one viewed in the video (p = 0.019). No difference was found between
      motor and sensory strokes. In 11 patients there was an action observation
      associated increase in the amplitudes of motor evoked potentials in the affected
      side. In 15 patients there was an action observation-associated increase in motor
      evoked potentials amplitudes in the unaffected side. CONCLUSION: The results are
      potentially relevant for the use of action observation as a treatment strategy.

PMID- 24658284
TI  - Use of the Internet and mobile-based "apps" for sex-seeking among men who have
      sex with men in New York City.
AB  - The Internet continues to be a popular venue for men who have sex with men (MSM)
      to seek sexual partners. Increased sexual risk behavior has been linked to MSM
      who use the Internet to seek partners. However, there has been little research on
      how new mobile-based social networking applications ("apps") may affect sex
      seeking and sexual risk behaviors of MSM. One hundred twenty-six MSM in New York
      City were recruited to complete an online survey on the use of the Internet and
      other technology for sex-seeking. The authors collected data on variables of
      interest including sexual sensation seeking, gay identity affirmation,
      internalized homophobia, Internet/app use, and sexual behavior with men met via
      the Internet and mobile apps. Results indicated that men who use both the
      Internet and mobile apps to seek partners were younger and reported higher
      incomes (p<.05) than men who used the Internet only. There were no significant
      differences between the groups with regard to race, sexual sensation seeking, gay
      identity affirmation, or internalized homophobia, indicating that the use of
      mobile-based apps for sex-seeking may be simply an example of evolving
      technologies. These findings may provide insight for the feasibility and planning
      of effective mobile app-based HIV/STI programs for MSM.

PMID- 24658283
TI  - A genome-wide gene-environment interaction analysis for tobacco smoke and lung
      cancer susceptibility.
AB  - Tobacco smoke is the major environmental risk factor underlying lung
      carcinogenesis. However, approximately one-tenth smokers develop lung cancer in
      their lifetime indicating there is significant individual variation in
      susceptibility to lung cancer. And, the reasons for this are largely unknown. In
      particular, the genetic variants discovered in genome-wide association studies
      (GWAS) account for only a small fraction of the phenotypic variations for lung
      cancer, and gene-environment interactions are thought to explain the missing
      fraction of disease heritability. The ability to identify smokers at high risk of
      developing cancer has substantial preventive implications. Thus, we undertook a
      gene-smoking interaction analysis in a GWAS of lung cancer in Han Chinese
      population using a two-phase designed case-control study. In the discovery phase,
      we evaluated all pair-wise (591 370) gene-smoking interactions in 5408 subjects
      (2331 cases and 3077 controls) using a logistic regression model with covariate
      adjustment. In the replication phase, promising interactions were validated in an
      independent population of 3023 subjects (1534 cases and 1489 controls). We
      identified interactions between two single nucleotide polymorphisms and smoking.
      The interaction P values are 6.73 * 10(-) (6) and 3.84 * 10(-) (6) for rs1316298
      and rs4589502, respectively, in the combined dataset from the two phases. An
      antagonistic interaction (rs1316298-smoking) and a synergetic interaction
      (rs4589502-smoking) were observed. The two interactions identified in our study
      may help explain some of the missing heritability in lung cancer susceptibility
      and present strong evidence for further study of these gene-smoking interactions,
      which are benefit to intensive screening and smoking cessation interventions.

PMID- 24658285
TI  - Investigation on the structure and upconversion fluorescence of Yb3+/Ho3+ co
      doped fluorapatite crystals for potential biomedical applications.
AB  - Rare-earth Yb(3+) and Ho(3+) co-doped fluorapatite (FA:Yb(3+)/Ho(3+)) crystals
      were prepared by hydrothermal synthesis, and their structure, upconversion
      properties, cell proliferation and imaging were investigated. The synthesized
      crystals, with a size of 16 by 286 nm, have a hexagonal crystal structure of
      classic FA and a Ca/Yb/Ho molar ratio of 100/16/2.1. Several reasonable
      Yb(3+)/Ho(3+) -embedding lattice models along the fluorine channel of the FA
      crystal cell are proposed for the first time, such as models for
      (Ca7YbHo(c))(PO4)6F2 and (Ca6YbHoNa2)(PO4)6F2. The activated FA:Yb(3+)/Ho(3+)
      crystals were found to exhibit distinct upconversion fluorescence. The 543- and
      654-nm signals in the emission spectra could be assigned, respectively, to the
      (5)F4 ((5)S2) - (5)I8 and (5)F5 - (5)I8 transitions of holmium via 980-nm near
      infrared excitation and the energy transfer of ytterbium. After the surfaces were
      grafted with hydrophilic dextran, the crystals displayed clear fluorescent cell
      imaging. Thus, the prepared novel FA:Yb(3+)/Ho(3+) upconversion fluorescent
      crystals have potential applications in the biomedical field.

PMID- 24658286
TI  - Noninvasive peroneal sensory and motor nerve conduction recordings in the rabbit
      distal hindlimb: feasibility, variability and neuropathy measure.
AB  - The peroneal nerve anatomy of the rabbit distal hindlimb is similar to humans,
      but reports of distal peroneal nerve conduction studies were not identified with
      a literature search. Distal sensorimotor recordings may be useful for studying
      rabbit models of length-dependent peripheral neuropathy. Surface electrodes were
      adhered to the dorsal rabbit foot overlying the extensor digitorum brevis muscle
      and the superficial peroneal nerve. The deep and superficial peroneal nerves were
      stimulated above the ankle and the common peroneal nerve was stimulated at the
      knee. The nerve conduction studies were repeated twice with a one-week intertest
      interval to determine measurement variability. Intravenous vincristine was used
      to produce a peripheral neuropathy. Repeat recordings measured the response to
      vincristine. A compound muscle action potential and a sensory nerve action
      potential were evoked in all rabbits. The compound muscle action potential mean
      amplitude was 0.29 mV (SD +/- 0.12) and the fibula head to ankle mean motor
      conduction velocity was 46.5 m/s (SD +/- 2.9). The sensory nerve action potential
      mean amplitude was 22.8 MUV (SD +/- 2.8) and the distal sensory conduction
      velocity was 38.8 m/s (SD +/- 2.2). Sensorimotor latencies and velocities were
      least variable between two test sessions (coefficient of variation  =  2.6-5.9%),
      sensory potential amplitudes were intermediate (coefficient of variation  = 
      11.1%) and compound potential amplitudes were the most variable (coefficient of
      variation  = 19.3%). Vincristine abolished compound muscle action potentials and
      reduced sensory nerve action potential amplitudes by 42-57% while having little
      effect on velocity. Rabbit distal hindlimb nerve conduction studies are feasible
      with surface recordings and stimulation. The evoked distal sensory potentials
      have amplitudes, configurations and recording techniques that are similar to
      humans and may be valuable for measuring large sensory fiber function in chronic
      models of peripheral neuropathies. 

PMID- 24658287
TI  - Racial and ethnic differences in factors related to workplace violence
      victimization.
AB  - Workplace violence (WPV) is a significant public health concern affecting all
      racial or ethnic groups. This study examined whether different racial/ethnic
      groups differed in vulnerability to WPV exposure and utilization of resources at
      the workplace. This cross-sectional research focused on White, Black, and Asian
      nursing employees (N = 2,033) employed in four health care institutions in a mid
      Atlantic U.S. metropolitan area. Whereas childhood physical abuse was
      significantly related to risk of WPV among workers from all racial/ethnic
      backgrounds, intimate partner abuse was a significant factor for Asians and
      Whites. Blacks and Asians were found to be less likely than Whites to be
      knowledgeable about WPV resources or use resources to address WPV. Services to
      address past trauma, and education and training opportunities for new workers may
      reduce risk of WPV and promote resource utilization among minority workers. 

PMID- 24658288
TI  - Nurses' comfort with touch and workplace well-being.
AB  - Touch is an essential part of caregiving and has been proved to be useful to
      reduce pain. Nevertheless, little attention has been paid to nurses' perceptions
      of touch. The aim of this article was to examine the relationship between nurses'
      feelings of comfort with touch and their well-being at work. A sample of 241
      nurses attending a pain management training course completed a questionnaire,
      including the following measures: Comfort with Touch (CT) scale (task-oriented
      contact, touch promoting physical comfort, touch providing emotional
      containment), Maslach Burnout Inventory (MBI; emotional exhaustion, cynicism),
      and Job Satisfaction. Results of structural equation models showed that touch
      providing emotional containment was the main predictor of emotional exhaustion.
      Emotional exhaustion, in turn, was positively related to cynicism and negatively
      related to job satisfaction. In addition, the direct path from touch providing
      emotional containment to cynicism was significant. Practical implications of the
      findings are discussed. 

PMID- 24658289
TI  - Measuring coping in pregnant minority women.
AB  - Coping strategies may help explain why some minority women experience more stress
      and poorer birth outcomes, so a psychometrically sound instrument to assess
      coping is needed. We examined the psychometric properties, readability, and
      correlates of coping in pregnant Black (n = 186) and Hispanic (n = 220) women
      using the Brief COPE. Exploratory and confirmatory factor analysis tested
      psychometric properties. The Flesch-Kincaid Reading Level test assessed
      readability. Linear regression models tested correlates of coping. Findings
      suggested two factors for the questionnaire: active and disengaged coping, as
      well as adequate reliability, validity, and readability level. For disengaged
      coping, Cronbach's alpha was .78 (English) and .70 (Spanish), and for active
      coping .86 (English) and .92 (Spanish). A two group confirmatory factor analysis
      revealed both minority groups had equivalent factor loadings. The reading level
      was at the sixth grade. Age, education, and gravidity were all found to be
      significant correlates with active coping. 

PMID- 24658290
TI  - Interdisciplinary Rounds and Structured Communication Reduce Re-Admissions and
      Improve Some Patient Outcomes.
AB  - Hospital communication is more than access to information. Among staff, it is
      about achieving situation awareness-an understanding of a patient's current
      condition and likely trajectory. In the multidisciplinary context of providing
      care, structure, consistency, and repeatability of communication will enable a
      shared understanding of the patient and plan, leading to improved patient
      satisfaction and outcomes. This was tested using the Situation-Background
      Assessment-Recommendation (SBAR) protocol, a re-admissions risk assessment and
      daily interdisciplinary rounds (IDR) in the medical/surgical units of a hospital.
      The impact of these interventions on patient satisfaction, Foley catheter removal
      compliance, and patient re-admission rates was assessed. Over the 3 year period,
      Foley compliance improved from 78% to 94%, and re-admissions decreased from 14.5%
      to 2.1%, both significant. Patient satisfaction trended positively, but was not
      significant. These results support the value of SBAR and IDR, and are advocated
      to improve situation awareness and maintain focus on key patient data.

PMID- 24658291
TI  - Functional connectivity among spikes in low dimensional space during working
      memory task in rat.
AB  - Working memory (WM) is critically important in cognitive tasks. The functional
      connectivity has been a powerful tool for understanding the mechanism underlying
      the information processing during WM tasks. The aim of this study is to
      investigate how to effectively characterize the dynamic variations of the
      functional connectivity in low dimensional space among the principal components
      (PCs) which were extracted from the instantaneous firing rate series. Spikes were
      obtained from medial prefrontal cortex (mPFC) of rats with implanted
      microelectrode array and then transformed into continuous series via
      instantaneous firing rate method. Granger causality method is proposed to study
      the functional connectivity. Then three scalar metrics were applied to identify
      the changes of the reduced dimensionality functional network during working
      memory tasks: functional connectivity (GC), global efficiency (E) and casual
      density (CD). As a comparison, GC, E and CD were also calculated to describe the
      functional connectivity in the original space. The results showed that these
      network characteristics dynamically changed during the correct WM tasks. The
      measure values increased to maximum, and then decreased both in the original and
      in the reduced dimensionality. Besides, the feature values of the reduced
      dimensionality were significantly higher during the WM tasks than they were in
      the original space. These findings suggested that functional connectivity among
      the spikes varied dynamically during the WM tasks and could be described
      effectively in the low dimensional space. 

PMID- 24658292
TI  - The effect of branched versus linear alkyl side chains on the bulk heterojunction
      photovoltaic performance of small molecules containing both benzodithiophene and
      thienopyrroledione.
AB  - To evaluate the effect of side chain characteristics on the photovoltaic
      performance of small molecules containing both benzodithiophene (BDT) and
      thienopyrroledione (TPD), we designed and synthesized two such molecules, one
      containing a branched 2-ethylhexyl (2EH) side chain on the BDT unit (BDTEH-TTPD)
      and the other containing a linear n-octyl (C8) side chain on the BDT unit (BDTO
      TTP). The optical and electrochemical properties and crystalline structures of
      these molecules were examined. Compared to BDTO-TTPD, BDTEH-TTPD, showed stronger
      light absorption, longer-range ordering and shorter pi-pi stacking distances
      between backbones. As a result, the power conversion efficiency of a bulk
      heterojunction solar cell based on BDTEH-TTPD (2.40%) was substantially higher
      than that of the BDTO-TTPD device (1.12%).

PMID- 24658293
TI  - Associations between beliefs about the causes of mental disorders and
      stigmatising attitudes: Results of a national survey of the Australian public.
AB  - OBJECTIVE: To examine the associations between beliefs about the causes of
      depression, schizophrenia, social phobia and post-traumatic stress disorder
      (PTSD) and stigmatising attitudes towards people with these disorders. METHODS:
      In 2011, telephone interviews were carried out with 6019 Australians aged 15 or
      over. Participants were presented with a case vignette describing either
      depression, depression with suicidal thoughts, early schizophrenia, chronic
      schizophrenia, social phobia or PTSD. Participants were asked about their beliefs
      about the causes of these disorders and about their personally held stigmatising
      attitudes, stigmatising attitudes perceived in others and the desire for social
      distance from the person described in the vignette. RESULTS: Belief in a weak or
      nervous personality as the cause of mental disorders was most consistently
      associated with personal stigma, perceived stigma and desire for social distance
      across vignettes. Belief in biogenetic causes was associated with a decreased
      belief in mental disorders as due to weakness rather than sickness, but was not
      linked to either a decreased or increased belief in dangerousness and
      unpredictability or desire for social distance. Belief in physical causes was
      associated with an increased belief in mental disorders as due to weakness rather
      than sickness. Belief in psychosocial causes had no consistent associations with
      stigma. CONCLUSIONS: Explaining mental disorders as due to personality
      characteristics is a more important factor in stigma than either biogenetic or
      psychosocial explanations.

PMID- 24658294
TI  - Depression and chronic kidney disease: A review for clinicians.
AB  - OBJECTIVE: To review the recent academic literature surrounding the prevalence,
      aetiopathology, associations and management of depression in chronic kidney
      disease (CKD), in order to provide a practical and up-to-date resource for
      clinicians. METHODS: We conducted electronic searches of the following databases:
      MEDLINE, EMBASE and PsycINFO. The main search terms were: depression, mood
      disorders, depressive disorder, mental illness, in combination with kidney
      disease, renal insufficiency, dialysis, kidney failure. Separate searches were
      conducted regarding antidepressant use in CKD. RESULTS: A number of recent, large
      and well-conducted studies have confirmed markedly raised rates of depression
      amongst those with CKD, with meta-analysis suggesting the prevalence of interview
      defined depression to be approximately 20%. The interactions between depression
      and CKD are complex, bidirectional and multifactorial. Depression in CKD has been
      shown to be associated with multiple poor outcomes, including increased mortality
      and hospitalisation rates, as well as poorer treatment compliance and quality of
      life. Clinical evaluation of depression in patients with CKD can be challenging;
      however, once a diagnosis is made, a range of treatment modalities can be
      considered. CONCLUSIONS: Depression is common in CKD and is associated with a
      significant risk of adverse outcomes. Given the importance of this issue, there
      is now an urgent need for well-conducted randomised trials of interventions for
      depression in CKD in order to provide information on the safety and efficacy of
      treatments.

PMID- 24658295
TI  - Agomelatine-associated manic switch in bipolar depression: a case report.

PMID- 24658296
TI  - RNA elements in open reading frames of the bluetongue virus genome are essential
      for virus replication.
AB  - Members of the Reoviridae family are non-enveloped multi-layered viruses with a
      double stranded RNA genome consisting of 9 to 12 genome segments. Bluetongue
      virus is the prototype orbivirus (family Reoviridae, genus Orbivirus), causing
      disease in ruminants, and is spread by Culicoides biting midges. Obviously,
      several steps in the Reoviridae family replication cycle require virus specific
      as well as segment specific recognition by viral proteins, but detailed processes
      in these interactions are still barely understood. Recently, we have shown that
      expression of NS3 and NS3a proteins encoded by genome segment 10 of bluetongue
      virus is not essential for virus replication. This gave us the unique opportunity
      to investigate the role of RNA sequences in the segment 10 open reading frame in
      virus replication, independent of its protein products. Reverse genetics was used
      to generate virus mutants with deletions in the open reading frame of segment 10.
      Although virus with a deletion between both start codons was not viable,
      deletions throughout the rest of the open reading frame led to the rescue of
      replicating virus. However, all bluetongue virus deletion mutants without
      functional protein expression of segment 10 contained inserts of RNA sequences
      originating from several viral genome segments. Subsequent studies showed that
      these RNA inserts act as RNA elements, needed for rescue and replication of
      virus. Functionality of the inserts is orientation-dependent but is independent
      from the position in segment 10. This study clearly shows that RNA in the open
      reading frame of Reoviridae members does not only encode proteins, but is also
      essential for virus replication. 

PMID- 24658297
TI  - Fall-related risk factors and heel quantitative ultrasound in the assessment of
      hip fracture risk: a 10-year follow-up of a nationally representative adult
      population sample.
AB  - Maximal walking speed and quantitative ultrasound index (QUI) were significant
      and independent predictors of hip fracture among subjects aged >= 55 years. A
      model including readily available variables along with simple fall-related
      factors may be clinically useful in the assessment of hip fracture risk even
      without a QUI measurement. INTRODUCTION: This study assessed fall-related risk
      factors along with heel bone quantitative ultrasound (QUS) measurements for the
      prediction of hip fracture during a mean follow-up of 9.8 years in a nationally
      representative population sample. METHODS: The study population consisted of
      2,300 subjects (1,331 women and 969 men) aged 55 years or over, who had
      participated in a comprehensive health survey in 2000-2001. Information on the
      subjects' health and fall-related risk factors was obtained with interviews,
      questionnaires and tests carried out by specially trained professionals. QUS
      measurements were made by means of the Hologic Sahara device. First emerging
      cases of hip fracture were identified from the National Hospital Discharge
      Register. RESULTS: During the follow-up, 96 subjects sustained a hip fracture.
      Slow maximal walking speed, low quantitative ultrasound index (QUI), high age,
      tallness, short waist circumference, Parkinson's disease and the number of
      central nervous system active medication were significant and independent
      predictors of hip fracture. The model including all of these risk factors
      explained 68 % of the variation in hip fracture risk. Excluding QUI from this
      model reduced the percentage to 66%. CONCLUSIONS: Maximal walking speed and QUI
      were significant and independent predictors of hip fracture. A model including
      readily available variables such as age, gender, height and waist circumference
      along with simple fall-related factors may be of clinical use in the assessment
      of hip fracture risk even without a QUS measurement.

PMID- 24658298
TI  - A pilot quantitative study of topographic correlation between reticular
      pseudodrusen and the choroidal vasculature using en face optical coherence
      tomography.
AB  - PURPOSE: To analyze the topographic correlation between reticular pseudodrusen
      (RPD) visualized on infrared reflectance (IR) and choroidal vasculature using en
      face volumetric spectral-domain optical coherence tomography (SD-OCT). METHODS: A
      masked observer marked individual RPD on IR images using ImageJ (NIH, Bethesda,
      MD). Using the macular volume scan (Cirrus, Carl Zeiss Meditec Inc, Dublin, CA),
      the RPE slab function was used to generate a C-scan of the most superficial
      choroidal vasculature. An independent masked grader created a topographic binary
      map of the choroidal vasculature by thresholding the en-face image, which was
      overlaid onto the IR map of RPD. For each IR image, ImageJ was used to generate a
      random set of dots as "control lesions". RESULTS: 17 eyes of 11 patients (78+/
      13.7 years) with RPD were analyzed. The average number of RPD lesions identified
      on IR images was 414+/-71.5, of which 49.6+/-4.3% were located overlying the
      choroidal vasculature, compared to 45.4+/-4.0% in controls (p = 0.014). 50.4+/
      4.3% of lesions overlay the choroidal stroma, of which 76.5+/-3.1% were <=3
      pixels from the choroidal vessels. The percentage of RPD lesions located within
      <=3 pixels from the choroidal vasculature was significantly greater than the
      percentage located >=7 pixels away. (p<0.0001). Compared to controls (71.6+/
      3.8%), RPD were more likely to be located <=3 pixels away from choroidal vessels
      (p = 0.014). In contrast, control lesions were more likely to be >=7 pixels away
      from choroidal vessels than RPD (9.1+/-1.9% vs. 4.8+/-1.2%, respectively, p =
      0.002). CONCLUSIONS: Our analysis shows that RPD lesions follow the underlying
      choroidal vasculature. Approximately half the RPD directly overlay the choroidal
      vessels and the majority of the remaining lesions were <=3 pixels (<=30 microns)
      from the vessel edge, supporting the hypothesis that RPD maybe related to
      pathologic changes at the choroidal level.

PMID- 24658299
TI  - Flexible membranes of Ag-nanosheet-grafted polyamide-nanofibers as effective 3D
      SERS substrates.
AB  - We report on a synthetic approach to produce self-supported flexible surface
      enhanced Raman scattering (SERS) active membranes consisting of polyamide (PA)
      nanofibers grafted with vertical Ag-nanosheets, via a combinatorial process of
      electrospinning PA-nanofiber membranes, assembling Au-nanoparticles on the PA
      nanofibers as seeds for subsequent growth of Ag-nanosheets, and electrodepositing
      Ag-nanosheets on the electrospun PA-nanofibers. As a high density of Ag
      nanosheets are vertically grown around each PA-nanofiber in the three-dimensional
      (3D) networked PA-nanofiber membranes, homogeneous nano-scaled gaps between the
      neighboring Ag-nanosheets are formed, leading to a high density of 3D SERS "hot
      spots" within the Ag-nanosheet-grafted PA-nanofiber membranes. The Ag-nanosheet
      grafted PA-nanofiber membranes demonstrate high SERS activity with excellent
      Raman signal reproducibility for rhodamine 6G over the whole membrane. For a SERS
      based trial analysis of polychlorinated biphenyls (PCBs, a kind of global
      environmental hazard), the 3D SERS substrate membranes are modified with mono-6
      beta-cychlodextrin to effectively capture PCB molecules. As a result, not only a
      low concentration down to 10(-6) M is reached, but also two congeners of PCBs in
      their mixed solution are identified, showing promising potential in SERS-based
      rapid detection of trace organic pollutants such as PCBs in the environment. 

PMID- 24658300
TI  - Cornea and ocular surface disease: application of cutting-edge optometric
      research.
AB  - : Clinician-scientists bridge the gap between basic research and patient care. At
      the 2012 Annual Meeting, a symposium highlighting the application of cutting-edge
      optometric research within the anterior segment was held to present and discuss
      some of the recent basic scientific advances that will both shape and guide the
      development of future clinical care practices. This article summarizes this work,
      bringing together four experts, all clinician-scientists in the field of cornea
      and ocular surface. Collectively, this work provides new insights to clinicians
      and researchers alike, as well as brings forth a greater appreciation of the
      impact of ongoing optometric bench research in advancing clinical care. 

PMID- 24658301
TI  - Recent weather extremes and impacts on agricultural production and vector-borne
      disease outbreak patterns.
AB  - We document significant worldwide weather anomalies that affected agriculture and
      vector-borne disease outbreaks during the 2010-2012 period. We utilized 2000-2012
      vegetation index and land surface temperature data from NASA's satellite-based
      Moderate Resolution Imaging Spectroradiometer (MODIS) to map the magnitude and
      extent of these anomalies for diverse regions including the continental United
      States, Russia, East Africa, Southern Africa, and Australia. We demonstrate that
      shifts in temperature and/or precipitation have significant impacts on vegetation
      patterns with attendant consequences for agriculture and public health. Weather
      extremes resulted in excessive rainfall and flooding as well as severe drought,
      which caused ~10 to 80% variation in major agricultural commodity production
      (including wheat, corn, cotton, sorghum) and created exceptional conditions for
      extensive mosquito-borne disease outbreaks of dengue, Rift Valley fever, Murray
      Valley encephalitis, and West Nile virus disease. Analysis of MODIS data provided
      a standardized method for quantifying the extreme weather anomalies observed
      during this period. Assessments of land surface conditions from satellite-based
      systems such as MODIS can be a valuable tool in national, regional, and global
      weather impact determinations. 

PMID- 24658302
TI  - Role of BH3-only molecules Bim and Puma in beta-cell death in Pdx1 deficiency.
AB  - Mutations in pancreatic duodenal homeobox-1 (PDX1) are associated with diabetes
      in humans. Pdx1-haploinsufficient mice develop diabetes due to an increase in
      beta-cell death leading to reduced beta-cell mass. For definition of the
      molecular link between Pdx1 deficiency and beta-cell death, Pdx1
      haploinsufficient mice in which the genes for the BH3-only molecules Bim and Puma
      had been ablated were studied on a high-fat diet. Compared with Pdx1(+/-) mice,
      animals haploinsufficient for both Pdx1 and Bim or Puma genes showed improved
      glucose tolerance, enhanced beta-cell mass, and reduction in the number of TUNEL
      positive cells in islets. These results suggest that Bim and Puma ablation
      improves beta-cell survival in Pdx1(+/-) mice. For exploration of the mechanisms
      responsible for these findings, Pdx1 gene expression was knocked down in mouse
      MIN6 insulinoma cells resulting in apoptotic cell death that was found to be
      associated with increased expression of BH3-only molecules Bim and Puma. If the
      upregulation of Bim and Puma that occurs during Pdx1 suppression was prevented,
      apoptotic beta-cell death was reduced in vitro. These results suggest that Bim
      and Puma play an important role in beta-cell apoptosis in Pdx1-deficient
      diabetes. 

PMID- 24658303
TI  - Glucagon-like peptide 1 recruits muscle microvasculature and improves insulin's
      metabolic action in the presence of insulin resistance.
AB  - Glucagon-like peptide 1 (GLP-1) acutely recruits muscle microvasculature,
      increases muscle delivery of insulin, and enhances muscle use of glucose,
      independent of its effect on insulin secretion. To examine whether GLP-1
      modulates muscle microvascular and metabolic insulin responses in the setting of
      insulin resistance, we assessed muscle microvascular blood volume (MBV), flow
      velocity, and blood flow in control insulin-sensitive rats and rats made insulin
      resistant acutely (systemic lipid infusion) or chronically (high-fat diet [HFD])
      before and after a euglycemic-hyperinsulinemic clamp (3 mU/kg/min) with or
      without superimposed systemic GLP-1 infusion. Insulin significantly recruited
      muscle microvasculature and addition of GLP-1 further expanded muscle MBV and
      increased insulin-mediated glucose disposal. GLP-1 infusion potently recruited
      muscle microvasculature in the presence of either acute or chronic insulin
      resistance by increasing muscle MBV. This was associated with an increased muscle
      delivery of insulin and muscle interstitial oxygen saturation. Muscle insulin
      sensitivity was completely restored in the presence of systemic lipid infusion
      and significantly improved in rats fed an HFD. We conclude that GLP-1 infusion
      potently expands muscle microvascular surface area and improves insulin's
      metabolic action in the insulin-resistant states. This may contribute to improved
      glycemic control seen in diabetic patients receiving incretin-based therapy. 

PMID- 24658304
TI  - Control of insulin secretion by cholinergic signaling in the human pancreatic
      islet.
AB  - Acetylcholine regulates hormone secretion from the pancreatic islet and is thus
      crucial for glucose homeostasis. Little is known, however, about acetylcholine
      (cholinergic) signaling in the human islet. We recently reported that in the
      human islet, acetylcholine is primarily a paracrine signal released from alpha
      cells rather than primarily a neural signal as in rodent islets. In this study,
      we demonstrate that the effects acetylcholine produces in the human islet are
      different and more complex than expected from studies conducted on cell lines and
      rodent islets. We found that endogenous acetylcholine not only stimulates the
      insulin-secreting beta-cell via the muscarinic acetylcholine receptors M3 and M5,
      but also the somatostatin-secreting delta-cell via M1 receptors. Because
      somatostatin is a strong inhibitor of insulin secretion, we hypothesized that
      cholinergic input to the delta-cell indirectly regulates beta-cell function.
      Indeed, when all muscarinic signaling was blocked, somatostatin secretion
      decreased and insulin secretion unexpectedly increased, suggesting a reduced
      inhibitory input to beta-cells. Endogenous cholinergic signaling therefore
      provides direct stimulatory and indirect inhibitory input to beta-cells to
      regulate insulin secretion from the human islet. 

PMID- 24658308
TI  - Antibacterial drugs: Redesigned antibiotic combats drug-resistant tuberculosis.

PMID- 24658305
TI  - P21 activated kinases: structure, regulation, and functions.
AB  - The p21 activated kinases (Paks) are well known effector proteins for the Rho
      GTPases Cdc42 and Rac. The Paks contain 6 members, which fall into 2 families of
      proteins. The first family consists of Paks 1, 2, and 3, and the second consists
      of Paks 4, 5, and 6. While some of the Paks are ubiquitously expressed, others
      have more restrictive tissue specificity. All of them are found in the nervous
      system. Studies using cell culture, transgenic mice, and knockout mice, have
      revealed important roles for the Paks in cytoskeletal organization and in many
      aspects of cell growth and development. This review discusses the basic
      structures of the Paks, and their roles in cell growth, development, and in
      cancer. 

PMID- 24658309
TI  - Cancer: Live screening of immunotherapy targets.

PMID- 24658307
TI  - Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence
      treatment.
AB  - Cigarette smoking remains the most preventable cause of death and excess health
      care costs in the United States, and is a leading cause of death among
      alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic
      options are limited. Repositioning medications approved by the U.S. Food and Drug
      Administration (FDA) may efficiently provide clinicians with new treatment
      options. We developed a drug-repositioning paradigm using larval zebrafish
      locomotion and established predictive clinical validity using FDA-approved
      smoking cessation therapeutics. We evaluated 39 physician-vetted medications for
      nicotine-induced locomotor activation blockade. We further evaluated candidate
      medications for altered ethanol response, as well as in combination with
      varenicline for nicotine-response attenuation. Six medications specifically
      inhibited the nicotine response. Among this set, apomorphine and topiramate
      blocked both nicotine and ethanol responses. Both positively interact with
      varenicline in the Bliss Independence test, indicating potential synergistic
      interactions suggesting these are candidates for translation into Phase II
      clinical trials for smoking cessation. 

PMID- 24658310
TI  - Market watch: Upcoming market catalysts in Q2 2014.

PMID- 24658311
TI  - Neurodegenerative disease: Searching for the weak spots.

PMID- 24658312
TI  - A minimal representation of the self-assembly of virus capsids.
AB  - Viruses are biological nanosystems with a capsid of protein-made capsomer units
      that encloses and protects the genetic material responsible for their
      replication. Here we show how the geometrical constraints of the capsomer
      capsomer interaction in icosahedral capsids and the requirement of low
      frustration fix the form of the shortest and universal truncated multipolar
      expansion of the two-body interaction between capsomers. The structures of many
      of the icosahedral and related virus capsids are located as single lowest energy
      states of a potential energy surface built from this interaction. Our minimalist
      representation is consistent with other models known to produce a controllable
      and efficient self-assembly, and unveils relevant features of the natural design
      of the capsids. It promises to be very useful in physical virology and may also
      be of interest in fields of nanoscience and nanotechnology where similar hollow
      convex structures are relevant. 

PMID- 24658313
TI  - Emergence of spin-filter states in Pt-Fe nanowires.
AB  - Our theoretical study predicts the emergence of a new spin-filter state in one
      dimensional Pt-Fe bimetallic nanowires. The results show the existence of two
      transmission states in contracted "zig-zag" Pt-Fe nanowires with low and high
      transmission 1G0 and 3G0, correspondingly, and one transmission state in linear
      stretched nanowires with conductance 2G0. Our first principle calculations
      revealed the dependence of quantum conductance of Pt-Fe nanowires on their
      geometry and atomic structure. Thus we found that nanowire stretching up to the
      interatomic distance of 2.3 A leads to the transition of the wire from a "zig
      zag" to the linear configuration, leading to changes in the conductance
      properties of the wire, i.e. formation of a new spin-filter state. Our study
      shows also the emergence of a magnetic transition from ferromagnetic to
      antiferromagnetic states under wire stretching. We found that the spin-filter
      state exists only in "zig-zag" Pt-Fe nanowires in the ferromagnetic state.
      Moreover, the spin-polarization of quantum electron transport through Pt-Fe
      nanowires vanishes totally in linear stretched nanowires in an antiferromagnetic
      state. Our electronic structure calculation reveals the emergence of new
      hybridized states in the band structure of the Pt-Fe nanowire, which causes the
      formation of a new spin-filter state. 

PMID- 24658314
TI  - Mobility and satisfaction with lower-limb prostheses and orthoses among users in
      Sierra Leone: a cross-sectional study.
AB  - OBJECTIVES: To investigate patients' mobility and satisfaction with their lower
      limb prosthetic or orthotic device and related service delivery in Sierra Leone;
      to compare groups of patients regarding type and level of assistive device,
      gender, area of residence, income; and to identify factors associated with
      satisfaction with the assistive device and service. METHODS: A total of 139
      patients answered questionnaires, including the Quebec User Evaluation of
      Satisfaction with Assistive Technology questionnaire (QUEST 2.0). RESULTS: Eighty
      six percent of assistive devices were in use, but half needed repair. Thirty
      three percent of patients reported pain when using their assistive device.
      Patients had difficulties or could not walk at all on: uneven ground (65%); hills
      (75%); and stairs (66%). Patients were quite satisfied with their assistive
      device and the service (mean 3.7 out of 5 in QUEST), but reported 886 problems.
      Approximately half of the patients could not access services. In relation to
      mobility and service delivery, women, orthotic patients and patients using above
      knee assistive devices had the poorest results. The general condition of the
      assistive device and patients' ability to walk on uneven ground were associated
      with satisfaction with the assistive devices and service. CONCLUSION: Patients
      reported high levels of mobility while using their device although they
      experienced pain and difficulties walking on challenging surfaces. Limitations in
      the effectiveness of assistive devices and limited access to follow-up services
      and repairs were issues desired to be addressed.

PMID- 24658315
TI  - Liposome-encapsulated ISMN: a novel nitric oxide-based therapeutic agent against
      Staphylococcus aureus biofilms.
AB  - BACKGROUND: Staphylococcus aureus in its biofilm form has been associated with
      recalcitrant chronic rhinosinusitis with significant resistance to conventional
      therapies. This study aims to determine if liposomal-encapsulation of a precursor
      of the naturally occurring antimicrobial nitric oxide (NO) enhances its desired
      anti-biofilm effects against S. aureus, in the hope that improving its efficacy
      can provide an effective topical agent for future clinical use. METHODOLOGY: S.
      aureus ATCC 25923 biofilms were grown in-vitro using the Minimum Biofilm
      Eradication Concentration (MBEC) device and exposed to 3 and 60 mg/mL of the NO
      donor isosorbide mononitrate (ISMN) encapsulated into different anionic liposomal
      formulations based on particle size (unilamellar ULV, multilamellar MLV) and
      lipid content (5 and 25 mM) at 24 h and 5 min exposure times. Biofilms were
      viewed using Live-Dead Baclight stain and confocal scanning laser microscopy and
      quantified using the software COMSTAT2. RESULTS: At 3 and 60 mg/mL, ISMN-ULV
      liposomes had comparable and significant anti-biofilm effects compared to
      untreated control at 24 h exposure (p = 0.012 and 0.02 respectively). ULV blanks
      also had significant anti-biofilm effects at both 24 h and 5 min exposure (p =
      0.02 and 0.047 respectively). At 5 min exposure, 60 mg/mL ISMN-MLV liposomes
      appeared to have greater anti-biofilm effects compared to pure ISMN or ULV
      particles. Increasing liposomal lipid content improved the anti-biofilm efficacy
      of both MLV and ULVs at 5 min exposure. CONCLUSION: Liposome-encapsulated "nitric
      oxide" is highly effective in eradicating S. aureus biofilms in-vitro, giving
      great promise for use in the clinical setting to treat this burdensome infection.
      Further studies however are needed to assess its safety and efficacy in-vivo
      before clinical translation is attempted.

PMID- 24658316
TI  - The impact of the rate prior on Bayesian estimation of divergence times with
      multiple Loci.
AB  - Bayesian methods provide a powerful way to estimate species divergence times by
      combining information from molecular sequences with information from the fossil
      record. With the explosive increase of genomic data, divergence time estimation
      increasingly uses data of multiple loci (genes or site partitions). Widely used
      computer programs to estimate divergence times use independent and identically
      distributed (i.i.d.) priors on the substitution rates for different loci. The
      i.i.d. prior is problematic. As the number of loci (L) increases, the prior
      variance of the average rate across all loci goes to zero at the rate 1/L. As a
      consequence, the rate prior dominates posterior time estimates when many loci are
      analyzed, and if the rate prior is misspecified, the estimated divergence times
      will converge to wrong values with very narrow credibility intervals. Here we
      develop a new prior on the locus rates based on the Dirichlet distribution that
      corrects the problematic behavior of the i.i.d. prior. We use computer simulation
      and real data analysis to highlight the differences between the old and new
      priors. For a dataset for six primate species, we show that with the old i.i.d.
      prior, if the prior rate is too high (or too low), the estimated divergence times
      are too young (or too old), outside the bounds imposed by the fossil
      calibrations. In contrast, with the new Dirichlet prior, posterior time estimates
      are insensitive to the rate prior and are compatible with the fossil
      calibrations. We re-analyzed a phylogenomic data set of 36 mammal species and
      show that using many fossil calibrations can alleviate the adverse impact of a
      misspecified rate prior to some extent. We recommend the use of the new Dirichlet
      prior in Bayesian divergence time estimation. [Bayesian inference, divergence
      time, relaxed clock, rate prior, partition analysis.]. 

PMID- 24658317
TI  - Clinicopathological characteristics and prognosis-related factors of resectable
      pancreatic neuroendocrine tumors: a retrospective study of 104 cases in a single
      Chinese center.
AB  - OBJECTIVE: The purpose was to describe the clinicopathological characteristics of
      pancreatic neuroendocrine tumors (pNETs) and evaluate prognosis-related factors
      in potentially resectable pNETs. METHODS: The clinical data of 104 patients with
      pNETs who underwent surgery were retrospectively analyzed. RESULTS: The mean (SD)
      age was 49.8 (14.6) years. The percentages of TNM stages I, II, III, and IV
      tumors were 25.0%, 44.2%, 22.1%, and 8.7%, respectively. Twenty-seven cases were
      functional. Nonfunctional pNETs were more common in patients with large tumors,
      advanced age, higher mitotic count, neural invasion, extrapancreatic organ
      invasion, liver metastases, and advanced staging (P < 0.05). The 5-year overall
      survival rate was 93%. The relapse rate was 28.6% (28/98), and the mean (SD)
      relapse time was 38.7 (31.7) months. Reduced survival rate was associated with
      older patients (>60 years) (P = 0.026), patients with a higher Ki-67 index (>2%)
      (P = 0.024), regional lymph node metastases (P = 0.033), liver metastases (P =
      0.015), neural invasion (P = 0.017), necrosis (P = 0.042), and major vascular
      invasion (P = 0.023). Age of more than 60 years (P = 0.047; hazard ratio [HR],
      5.2), major vascular invasion (P = 0.030; HR, 5.8), and a Ki-67 index greater
      than 2% (P = 0.008; HR, 10.3) were independent predictors. CONCLUSIONS:
      Nonfunctional pNETs were more common with aggressive clinical presentation. Age
      of more than 60 years, major vascular invasion, and a Ki-67 index greater than 2%
      were independent predictive factors. Patients who underwent a potentially
      curative resection seemed to achieve long-term survival.

PMID- 24658318
TI  - Characterization of functional transient receptor potential melastatin 8 channels
      in human pancreatic ductal adenocarcinoma cells.
AB  - OBJECTIVE: Recently, the transient receptor potential melastatin 8 (TRPM8)
      channel has emerged as a putative biomarker for pancreatic ductal adenocarcinoma
      (PDA). This study aimed to evaluate the expression of TRPM8 and its modulation by
      specific agonists and antagonists in PDA cells. METHODS: We examined the protein
      expression of TRPM8 in 3 different PDA cell lines and compared it with a
      nontumoral epithelial cell line of human pancreatic origin using Western blotting
      and immunocytochemical analysis. To assess the function of TRPM8 channels, we
      measured the TRPM8 currents in whole-cell mode of the patch clamp technique. To
      explore the putative involvement of TRPM8 in cell migration, we investigated the
      motility of PDA cells using the scratch-wound assay. RESULTS: Pancreatic ductal
      adenocarcinoma cells express functional plasma membrane TRPM8 channels, which are
      responsive after exposure to agonists (menthol and icilin) and antagonists N-(3
      aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide
      hydrochloride salt. The silencing of TRPM8 expression by small interfering RNA
      augments the migration of PDA cells. Conversely, the activated form of TRPM8
      inhibits PDA cell motility. CONCLUSIONS: An unglycosylated TRPM8 protein is
      expressed and is functional in the membrane of PDA cells. Transient receptor
      potential melastatin 8 inhibits the migration of PDA cells, suggesting a putative
      role as a biomarker or target for this channel for PDA therapy.

PMID- 24658319
TI  - A comparative study of diagnostic scoring systems for autoimmune pancreatitis.
AB  - OBJECTIVE: Several diagnostic scoring systems for autoimmune pancreatitis (AIP)
      have been proposed including the Asian, HISORt (Histology, Imaging, Serology,
      Other organ involvement and Response to therapy), and International Consensus
      Diagnostic Criteria (ICDC), which have been compared by a few studies. We
      evaluated the diagnostic performance of these criteria in patients diagnosed with
      AIP between May 1992 and August 2011. METHODS: Scoring systems were applied
      retrospectively using data obtained in the initial evaluation period, before
      pancreatic resection was performed. RESULTS: One hundred fourteen cases with AIP
      were included. Eighty-two percent met the diagnostic criteria for AIP according
      to either the Asian, HISORt, or ICDC criteria. Only 33% met the Asian criteria,
      probably mainly related to a low rate of diagnostic pancreatography. In 18%, all
      scoring systems failed to confirm the diagnosis, even though these patients were
      considered to have a firm diagnosis of AIP. CONCLUSIONS: In this cohort of AIP
      patients, the 3 major diagnostic scoring systems for AIP proved to be
      complementary rather than overlapping. Our data indicate that one-fifth of our
      AIP patients do not meet any of these scoring systems. The ICDC, Asian, and
      HISORt criteria should be considered as useful clinical tools but not as
      criterion standard for the diagnosis.

PMID- 24658320
TI  - Differential expression of STAT1 and p21 proteins predicts pancreatic cancer
      progression and prognosis.
AB  - OBJECTIVE: The transcription factor Stat1 is a member of the family of signal
      transducers and transcription activators and responds to interferon-gamma
      stimulation. p21 is a p53-responsive gene for cell cycle regulation and mediates
      Stat1 antitumor activity. The aim of this study was to analyze their expression
      for prediction of pancreatic cancer progression and prognosis. METHODS: A total
      of 100 pancreatic adenocarcinoma tissue specimens were used for construction of a
      pancreatic cancer tissue microarray for immunohistochemical staining of Stat1 and
      p21 expression. RESULTS: Stat1 and p21 proteins were expressed in 88% (88/100)
      and 82% (82/100) of pancreatic adenocarcinoma tissue specimens, and the
      expression was inversely associated with tumor differentiation, clinical stages,
      and lymph node metastasis of pancreatic cancer. There was no association with
      age, tumor size, or invasion. Moreover, the Kaplan-Meier curve analysis showed
      that patients with higher Stat1 and p21 expression had better overall survival
      rates than those with low expression of Stat1 and p21 proteins. CONCLUSIONS: The
      loss of expression of Stat1 and p21 proteins corresponded to lymph node
      metastasis, advanced stage, tumor dedifferentiation, and poor prognosis in
      patients with pancreatic cancer.

PMID- 24658321
TI  - In-depth exploration of the photophysics of a trinuclear palladium complex.
AB  - A detailed theoretical and spectroscopic study on the electronically excited
      states of a trinuclear palladium complex is presented both in the gas phase and
      solution. The application of DFT and TDDFT methods as well as a variety of
      spectroscopic methods to the chosen complex [Pd3{Si(mt(Me))3}2] (1, mt(Me) =
      methimazole) leads to the first detailed analysis of the photophysics of a
      symmetric trinuclear complex. In combination with the calculations, energies,
      structures and lifetimes of the excited electronic states (with an (3)A1 state as
      the lowest one) are characterized by applying the resonant-2-photon-ionization
      method in a molecular beam experiment as well as luminescence, time-correlated
      single photon counting and excited state femtosecond absorption spectroscopy in
      solution. These investigations are of fundamental interest to analyze
      photophysical properties of metal containing complexes on a molecular level.

PMID- 24658322
TI  - LIN7A depletion disrupts cerebral cortex development, contributing to
      intellectual disability in 12q21-deletion syndrome.
AB  - Interstitial deletion of 12q21 has been reported in four cases, which share
      several common clinical features, including intellectual disability (ID), low-set
      ears, and minor cardiac abnormalities. Comparative genomic hybridization (CGH)
      analysis using the Agilent Human Genome CGH 180K array was performed with the
      genomic DNA from a two-year-old Japanese boy with these symptoms, as well as
      hypoplasia of the corpus callosum. Consequently, a 14 Mb deletion at 12q21.2
      q21.33 (nt. 77 203 574-91 264 613 bp), which includes 72 genes, was detected. Of
      these, we focused on LIN7A, which encodes a scaffold protein that is important
      for synaptic function, as a possible responsible gene for ID, and we analyzed its
      role in cerebral cortex development. Western blotting analyses revealed that Lin
      7A is expressed on embryonic day (E) 13.5, and gradually increases in the mouse
      brain during the embryonic stage. Biochemical fractionation resulted in the
      enrichment of Lin-7A in the presynaptic fraction. Suppression of Lin-7A
      expression by RNAi, using in utero electroporation on E14.5, delayed neuronal
      migration on postnatal day (P) 2, and Lin-7A-deficient neurons remained in the
      lower zone of the cortical plate and the intermediate zone. In addition, when Lin
      7A was silenced in cortical neurons in one hemisphere, axonal growth in the
      contralateral hemisphere was delayed; development of these neurons was disrupted
      such that one half did not extend into the contralateral hemisphere after leaving
      the corpus callosum. Taken together, LIN7A is a candidate gene responsible for
      12q21-deletion syndrome, and abnormal neuronal migration and interhemispheric
      axon development may contribute to ID and corpus callosum hypoplasia,
      respectively. 

PMID- 24658323
TI  - Motor unit firing rate patterns during voluntary muscle force generation: a
      simulation study.
AB  - OBJECTIVE: Muscle force is generated by a combination of motor unit (MU)
      recruitment and changes in the discharge rate of active MUs. There have been two
      basic MU recruitment and firing rate paradigms reported in the literature, which
      describe the control of the MUs during force generation. The first (termed the
      reverse 'onion skin' profile), exhibits lower firing rates for lower threshold
      units, with higher firing rates occurring in higher threshold units. The second
      (termed the 'onion skin' profile), exhibits an inverse arrangement, with lower
      threshold units reaching higher firing rates. APPROACH: Using a simulation of the
      MU activity in a hand muscle, this study examined the force generation capacity
      and the variability of the muscle force magnitude at different excitation levels
      of the MU pool under these two different MU control paradigms. We sought to
      determine which rate/recruitment scheme was more efficient for force generation,
      and which scheme gave rise to the lowest force variability. MAIN RESULTS: We
      found that the force output of both firing patterns leads to graded force output
      at low excitation levels, and that the force generation capacity of the two
      different paradigms diverged around 50% excitation. In the reverse 'onion skin'
      pattern, at 100% excitation, the force output reached up to 88% of maximum force,
      whereas for the 'onion skin' pattern, the force output only reached up to 54% of
      maximum force at 100% excitation. The force variability was lower at the low to
      moderate force levels under the 'onion skin' paradigm than with the reverse
      'onion skin' firing patterns, but this effect was reversed at high force levels.
      SIGNIFICANCE: This study captures the influence of MU recruitment and firing rate
      organization on muscle force properties, and our results suggest that the
      different firing organizations can be beneficial at different levels of voluntary
      muscle force generation and perhaps for different tasks.

PMID- 24658324
TI  - Comparison of xenobiotic metabolizing enzyme activities in ex vivo human skin and
      reconstructed human skin models from SkinEthic.
AB  - Skin function is not limited to a physical barrier. According to its total
      surface area, it is also considered as an extra-hepatic metabolizing organ. In
      vitro engineered human skins have been developed to replace limited ex vivo
      normal human skin samples (NHS). Thus, assessing and comparing skin models from
      SkinEthic [EpiskinTM, RHETM and the full thickness model (FTM)] with NHS in terms
      of metabolic capability are essential. The apparent activities of main cutaneous
      isoforms of cytochrome P450-dependent monooxygenases (CYP1A1/1B1, 2B6/2C18/2E1,
      3A5/3A7), esterase, glutathione-S-[(GST), A, M, P, T], N-acetyl-(NAT1), uridinyl
      diphosphate glucuronyl-(UDPGT 1A family) and sulfo-(SULT1A1) transferases were
      determined using probe substrates. Mean activities indicative of CYP1A1/1B1
      (expressed as pmol/mg protein/6 h) in RHETM (2.8) and FTM (2.6) were very similar
      to NHS (3.0) while EpiskinTM showed a higher activity (9.1). Activities of
      CYP3A5/3A7 in FTM (3.3) and EpiskinTM (3.6) were similar to NHS (3.8) while
      activity in RHETM (13.3) was higher. CYP2B6/2C18/2E1 activity was below LOQ (0.5)
      in all skin models and NHS. Comparable intrinsic metabolic clearances were
      measured between NHS and skin models for esterase, UDPGT, GST and NAT1
      activities. SULT1A1 activity toward probe substrates was not detected in skin
      models and observed at the limit of detection in NHS. Weak cytochrome P450
      dependent monooxygenases, high esterase and transferase activities suggested that
      NHS and skin models exhibited limited functionalization and much greater
      detoxification (hydrolytic and conjugating) capacities. These results demonstrate
      that skin models are similar to NHS in terms of metabolic functionality toward
      xenobiotics investigated and useful tools to assess both the local efficiency and
      safety of cosmetics.

PMID- 24658325
TI  - TCDD-induced chick cardiotoxicity is abolished by a selective cyclooxygenase-2
      (COX-2) inhibitor NS398.
AB  - Halogenated aromatic hydrocarbons, including 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), are known to cause severe heart defects in avian species. However, the
      mechanism of TCDD-induced chick cardiovascular toxicity is unclear. In this
      study, we investigated cyclooxygenase-2 (COX-2) as a possible mechanism of TCDD
      induced cardiotoxicity. Fertile chicken eggs were injected with TCDD and a COX-2
      selective inhibitor, NS398, and we investigated chick heart failure on day 10. We
      found that the chick heart to body weight ratio and atrial natriuretic factor
      mRNA expression were increased, but this increase was abolished with treatment of
      NS398. In addition, the morphological abnormality of an enlarged ventricle
      resulting from TCDD exposure was also abolished with co-treatment of TCDD and
      NS398. Our results suggested that TCDD-induced chick heart defects are mediated
      via the nongenomic pathway and that they do not require the genomic pathway.

PMID- 24658326
TI  - MerTK inhibition is a novel therapeutic approach for glioblastoma multiforme.
AB  - Glioblastoma is an aggressive tumor that occurs in both adult and pediatric
      patients and is known for its invasive quality and high rate of recurrence.
      Current therapies for glioblastoma result in high morbidity and dismal outcomes.
      The TAM subfamily of receptor tyrosine kinases includes Tyro3, Axl, and MerTK.
      Axl and MerTK exhibit little to no expression in normal brain but are highly
      expressed in glioblastoma and contribute to the critical malignant phenotypes of
      survival, chemosensitivity and migration. We have found that Foretinib, a RTK
      inhibitor currently in clinical trial, inhibited phosphorylation of TAM
      receptors, with highest efficacy against MerTK, and blocked downstream activation
      of Akt and Erk in adult and pediatric glioblastoma cell lines, findings that are
      previously unreported. Survival, proliferation, migration, and collagen invasion
      were hindered in vitro. Foretinib treatment in vivo abolished MerTK
      phosphorylation and reduced tumor growth 3-4 fold in a subcutaneous mouse model.
      MerTK targeted shRNA completely prevented intracranial and subcutaneous glioma
      growth further delineating the impact of MerTK inhibition on glioblastoma. Our
      findings provide additional target validation for MerTK inhibition in
      glioblastoma and demonstrate that robust MerTK inhibition can be achieved with
      the multi-kinase inhibitor Foretinib as an innovative and translational
      therapeutic approach to glioblastoma. 

PMID- 24658327
TI  - Molecular structure-optical property relationships for a series of non
      centrosymmetric two-photon absorbing push-pull triarylamine molecules.
AB  - This article reports on a comprehensive study of the two-photon absorption (2PA)
      properties of six novel push-pull octupolar triarylamine compounds as a function
      of the nature of the electron-withdrawing groups. These compounds present an
      octupolar structure consisting of a triarylamine core bearing two 3,3'
      bis(trifluoromethyl)phenyl arms and a third group with varying electron
      withdrawing strength (H < CN < CHO < NO2 < Cyet < Vin). The 2PA cross-sections,
      measured by using the femtosecond open-aperture Z-scan technique, showed
      significant enhancement from 45 up to 125 GM for the lowest energy band and from
      95 up to 270 GM for the highest energy band. The results were elucidated based on
      the large changes in the transition and permanent dipole moments and in terms of
      (i) EWG strength, (ii) degree of donor-acceptor charge transfer and (iii)
      electronic coupling between the arms. The 2PA results were eventually supported
      and confronted with theoretical DFT calculations of the two-photon transition
      oscillator strengths.

PMID- 24658328
TI  - Nanopatterned antimicrobial enzymatic surfaces combining biocidal and fouling
      release properties.
AB  - Surfaces incorporating the antimicrobial enzyme, lysozyme, have been previously
      demonstrated to effectively disrupt bacterial cellular envelopes. As with any
      surface active antimicrobial, however, lysozyme-expressing surfaces become
      limited in their utility by the accumulation of dead bacteria and debris.
      Surfaces modified with environmentally responsive polymers, on the other hand,
      have been shown to reversibly attach and release both live and dead bacterial
      cells. In this work, we combine the antimicrobial activity of lysozyme with the
      fouling release capability of the thermally responsive polymer, poly(N
      isopropylacrylamide) (PNIPAAm), which has a lower critical solution temperature
      (LCST) in water at ~32  degrees C. Nanopatterned PNIPAAm brushes were fabricated
      using interferometric lithography followed by surface-initiated polymerization.
      Lysozyme was then adsorbed into the polymer-free regions of the substrate between
      the brushes to achieve a hybrid surface with switchable antimicrobial activity
      and fouling-release ability in response to the change of temperature. The
      temperature triggered hydration and conformational change of the nanopatterned
      PNIPAAm brushes provide the ability to temporally regulate the spatial
      concealment and exposure of adsorbed lysozyme. The biocidal efficacy and release
      properties of the hybrid surface were tested against Escherichia coli K12 and
      Staphylococcus epidermidis. The hybrid surfaces facilitated the attachment of
      bacteria at 37  degrees C for E. coli and 25  degrees C for S. epidermidis and
      when the temperature is above the LCST, collapsed and dehydrated PNIPAAm chains
      expose lysozyme to kill attached bacteria. Changing temperature across the LCST
      of PNIPAAm (e.g. from 37  degrees C to 25  degrees C for E. coli or from 25 
      degrees C to 37  degrees C for S. epidermidis) to induce a hydration transition
      of PNIPAAm promoted the release of dead bacteria and debris from the surfaces
      upon mild shearing. These results suggest that nano-engineered surfaces can
      provide an effective way for actively mitigating short term bacterial biofouling.

PMID- 24658332
TI  - Phenotypic, genomic and functional characterization reveals no differences
      between CD138++ and CD138low subpopulations in multiple myeloma cell lines.
AB  - Despite recent advances in the treatment of multiple myeloma (MM), it remains an
      incurable disease potentially due to the presence of resistant myeloma cancer
      stem cells (MM-CSC). Although the presence of clonogenic cells in MM was
      described three decades ago, the phenotype of MM-CSC is still controversial,
      especially with respect to the expression of syndecan-1 (CD138). Here, we
      demonstrate the presence of two subpopulations--CD138++ (95-99%) and CD138low (1
      5%)--in eight MM cell lines. To find out possible stem-cell-like features, we
      have phenotypically, genomic and functionally characterized the two
      subpopulations. Our results show that the minor CD138low subpopulation is
      morphologically identical to the CD138++ fraction and does not represent a more
      immature B-cell compartment (with lack of CD19, CD20 and CD27 expression).
      Moreover, both subpopulations have similar gene expression and genomic profiles.
      Importantly, both CD138++ and CD138low subpopulations have similar sensitivity to
      bortezomib, melphalan and doxorubicin. Finally, serial engraftment in CB17-SCID
      mice shows that CD138++ as well as CD138low cells have self-renewal potential and
      they are phenotypically interconvertible. Overall, our results differ from
      previously published data in MM cell lines which attribute a B-cell phenotype to
      MM-CSC. Future characterization of clonal plasma cell subpopulations in MM
      patients' samples will guarantee the discovery of more reliable markers able to
      discriminate true clonogenic myeloma cells.

PMID- 24658329
TI  - Coordination of microbial metabolism.
AB  - Beyond fuelling cellular activities with building blocks and energy, metabolism
      also integrates environmental conditions into intracellular signals. The
      underlying regulatory network is complex and multifaceted: it ranges from slow
      interactions, such as changing gene expression, to rapid ones, such as the
      modulation of protein activity via post-translational modification or the
      allosteric binding of small molecules. In this Review, we outline the
      coordination of common metabolic tasks, including nutrient uptake, central
      metabolism, the generation of energy, the supply of amino acids and protein
      synthesis. Increasingly, a set of key metabolites is recognized to control
      individual regulatory circuits, which carry out specific functions of information
      input and regulatory output. Such a modular view of microbial metabolism
      facilitates an intuitive understanding of the molecular mechanisms that underlie
      cellular decision making. 

PMID- 24658333
TI  - Pressure pain thresholds increase after preconditioning 1 Hz repetitive
      transcranial magnetic stimulation with transcranial direct current stimulation.
AB  - BACKGROUND: The primary motor cortex (M1) is an effective target of non-invasive
      cortical stimulation (NICS) for pain threshold modulation. It has been suggested
      that the initial level of cortical excitability of M1 plays a key role in the
      plastic effects of NICS. OBJECTIVE: Here we investigate whether transcranial
      direct current stimulation (tDCS) primed 1 Hz repetitive transcranial magnetic
      stimulation (rTMS) modulates experimental pressure pain thresholds and if this is
      related to observed alterations in cortical excitability. METHOD: 15 healthy,
      male participants received 10 min 1 mA anodal, cathodal and sham tDCS to the left
      M1 before 15 min 1 Hz rTMS in separate sessions over a period of 3 weeks. Motor
      cortical excitability was recorded at baseline, post-tDCS priming and post-rTMS
      through recording motor evoked potentials (MEPs) from right FDI muscle. Pressure
      pain thresholds were determined by quantitative sensory testing (QST) through a
      computerized algometer, on the palmar thenar of the right hand pre- and post
      stimulation. RESULTS: Cathodal tDCS-primed 1 Hz-rTMS was found to reverse the
      expected suppressive effect of 1 Hz rTMS on cortical excitability; leading to an
      overall increase in activity (p<0.001) with a parallel increase in pressure pain
      thresholds (p<0.01). In contrast, anodal tDCS-primed 1 Hz-rTMS resulted in a
      corresponding decrease in cortical excitability (p<0.05), with no significant
      effect on pressure pain. CONCLUSION: This study demonstrates that priming the M1
      before stimulation of 1 Hz-rTMS modulates experimental pressure pain thresholds
      in a safe and controlled manner, producing a form of analgesia.

PMID- 24658334
TI  - Mechanisms of psychological distress following war in the former Yugoslavia: the
      role of interpersonal sensitivity.
AB  - While high prevalence rates of psychological symptoms have been documented in
      civilian survivors of war, little is known about the mechanisms by which trauma
      exposure might lead to poor psychological outcomes in these populations. One
      potential mechanism that may underpin the association between war-related
      traumatic experiences and psychopathology is interpersonal sensitivity. In the
      current study, we applied structural equation modeling to investigate the impact
      of interpersonal sensitivity on posttraumatic stress disorder (PTSD) symptoms,
      depression symptoms, and anger responses following exposure to war trauma. 3313
      survivors of the war in the former Yugoslavia were identified and selected using
      a multistage, probabilistic sampling frame and random walk technique.
      Participants were interviewed regarding trauma exposure, interpersonal
      sensitivity, and PTSD symptoms, depression symptoms, and anger responses.
      Structural equation modeling analyses revealed that the relationship between
      trauma and PTSD symptoms and depression symptoms was partly statistically
      mediated by interpersonal sensitivity. Further, findings indicated that the
      relationship between trauma and anger responses was fully statistically mediated
      by interpersonal sensitivity. These results suggest that interpersonal
      sensitivity may function as a key mechanism that contributes to psychopathology
      following trauma. 

PMID- 24658337
TI  - Mn-modified Bi2Ti2O7 photocatalysts: bandgap engineered multifunctional
      photocatalysts for hydrogen generation.
AB  - In this study, a hydrogen generation photocatalyst based on bismuth titanate
      (Bi2Ti2O7 - BTO) modified with manganese (Mn) has been developed. Mn of varying
      weight percent was added to construct a modified BTO catalyst (Mn_BTO), in order
      to enhance the opto-electronic and photocatalytic hydrogen generation
      capabilities of the pristine BTO. The structural, morphological, and optical
      properties of the photocatalysts were evaluated by X-ray diffraction (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      UV-visible spectrophotometry. The XRD, SEM, and TEM analyses indicate the
      formation of the pyrochlore BTO phase with particles of dimensions 30 +/- 10 nm.
      The UV-visible study revealed a reduction in the bandgap of Mn_BTO and enhanced
      absorption in the visible range, compared to the pristine BTO. The catalyst was
      optimized for maximum hydrogen generation from a water-methanol (sacrificial
      electron donor) system in a slurry reactor. The photocatalytic hydrogen evolution
      studies indicate that the Mn_BTO with up to 1 wt% Mn facilitates an optimal 140%
      increase in the hydrogen yield. The role of formic acid and formaldehyde as
      additives in photocatalytic hydrogen evolution has also been examined. The effect
      of Mn content, mechanistic overview, and reusability of the catalyst are
      discussed. 

PMID- 24658335
TI  - Gallotannin imposes S phase arrest in breast cancer cells and suppresses the
      growth of triple-negative tumors in vivo.
AB  - Triple-negative breast cancers are associated with poor clinical outcomes and new
      therapeutic strategies are clearly needed. Gallotannin (Gltn) has been previously
      demonstrated to have potent anti-tumor properties against cholangiocarcinoma in
      mice, but little is known regarding its capacity to suppress tumor outgrowth in
      breast cancer models. We tested Gltn for potential growth inhibitory properties
      against a variety of breast cancer cell lines in vitro. In particular, triple
      negative breast cancer cells display higher levels of sensitivity to Gltn. The
      loss of proliferative capacity in Gltn exposed cells is associated with slowed
      cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and
      further characterized by changes to proliferation related genes, such as cyclin
      D1 (CcnD1) as determined by Nanostring technology. Importantly, Gltn administered
      orally or via intraperitoneal (IP) injections greatly reduced tumor outgrowth of
      triple-negative breast cells from mammary fat pads without signs of toxicity. In
      conclusion, these data strongly suggest that Gltn represents a novel approach to
      treat triple-negative breast carcinomas. 

PMID- 24658338
TI  - BRCA1 exon 11 a model of long exon splicing regulation.
AB  - BRCA1 exon 11 is one of the biggest human exons, spanning 3426 bases. This gene
      is potentially involved in DNA repair as well as cell growth and cell cycle
      control. Exon 11 is regulated at the splicing level producing three main
      different combinations of BRCA1 mature transcripts; one including the whole of
      exon 11 (full isoform), one skipping the entire exon (D11 isoform), and one
      including only 117 base pairs of exon 11 (D11q isoform). Using minigene and
      deletion analyses, we have previously described important splicing regulatory
      sequences located at the beginning of this exon (5' end). We have now found
      additional important sequences located at its 3' end. In particular, we describe
      the presence of a strong splicing enhancer adjacent to the downstream 5' splice
      site, which minimizes competition from an upstream 5' splice site and so ensures
      long exon inclusion. Analyses of the proteins binding these RNA sequences have
      revealed that Tra2beta and hnRNP L are involved in the regulation of BRCA1 exon
      11 by influencing the recognition of donor sites. Interestingly, BRCA1 exon 11
      carrying deletion of the regulatory sequences bound by these factors also showed
      unexpected responses to up- or downregulation of these regulatory proteins,
      suggesting that they can also bind elsewhere in this large exon and elicit
      different effects on its recognition.   The identification of sequences and
      proteins relevant for the regulation of BRCA1 exon 11 now provides better
      knowledge on how this exon is recognized and may represent an important step
      toward understanding how large exons are regulated. 

PMID- 24658339
TI  - Deswelling of ultrathin molecular layer-by-layer polyamide water desalination
      membranes.
AB  - The selective layer of pressure-induced water desalination membranes is an
      ultrathin and highly crosslinked aromatic polyamide (PA) film that separates salt
      from water based on differences in permeability, which is a product of
      diffusivity and solubility. Characterizing the transport properties of the
      selective layer is necessary in understanding its permselective performance.
      However, measuring transport of ultrathin films in general is nontrivial. Here,
      Poroelastic Relaxation Indentation (PRI) is employed as a simple deswelling
      technique for measuring the transport properties of these ultrathin selective
      layers. 

PMID- 24658340
TI  - A size dependent discontinuous decay rate for the exciton emission in ZnO quantum
      dots.
AB  - The time resolved UV-fluorescence in ZnO quantum dots has been investigated using
      femtosecond laser spectroscopy. The measurements were performed as a function of
      particle size for particles between 3 and 7 nm in diameter, which are in the
      quantum confined regime. A red shift in the fluorescence maximum is seen while
      increasing the particle size, which correlates with the shift in band gap due to
      quantum confinement. The energy difference between the UV-fluorescence and the
      band gap does, however, increase for the smaller particles. For 3.7 nm particles
      the fluorescence energy is 100 meV smaller than the band gap energy, whereas it
      is only 20 meV smaller for the largest particles. This indicates a stabilization
      of the excitons in the smallest particles. The lifetime of the UV fluorescence is
      in the picosecond time scale and interestingly, it is discontinuous with respect
      to particle size. For the smallest particles, the exciton emission life time
      reaches 30 ps, which is three times longer than that for the largest particles.
      This demonstrates a transition between two different mechanisms for the UV
      fluorescence. We suggest that this is an effect of surface trapping and
      stabilization of the excitons occurring in the smallest particles but not in the
      larger ones. We also discuss the time scale limit for slowed hot carrier dynamics
      in ensembles of quantum confined ZnO particles. 

PMID- 24658341
TI  - Stroke Self-efficacy Questionnaire: a Rasch-refined measure of confidence post
      stroke.
AB  - OBJECTIVE: Measuring self-efficacy during rehabilitation provides an important
      insight into understanding recovery post stroke. A Rasch analysis of the Stroke
      Self-efficacy Questionnaire (SSEQ) was undertaken to establish its use as a
      clinically meaningful and scientifically rigorous measure. METHODS: One hundred
      and eighteen stroke patients completed the SSEQ with the help of an interviewer.
      Participants were recruited from local acute stroke units and community stroke
      rehabilitation teams. Data were analysed with confirmatory factor analysis
      conducted using AMOS and Rasch analysis conducted using RUMM2030 software.
      RESULTS: Confirmatory factor analysis and Rasch analyses demonstrated the
      presence of two separate scales that measure stroke survivors' self-efficacy
      with: i) self-management and ii) functional activities. Guided by Rasch analyses,
      the response categories of these two scales were collapsed from an 11-point to a
      4-point scale. Modified scales met the expectations of the Rasch model. Items
      satisfied the Rasch requirements (overall and individual item fit, local response
      independence, differential item functioning, unidimensionality). Furthermore, the
      two subscales showed evidence of good construct validity. CONCLUSIONS: The new
      SSEQ has good psychometric properties and is a clinically useful assessment of
      self-efficacy after stroke. The scale measures stroke survivors' self-efficacy
      with self-management and activities as two unidimensional constructs. It is
      recommended for use in clinical and research interventions, and in evaluating
      stroke self-management interventions.

PMID- 24658342
TI  - Pleural procedures and patient safety: a national BTS audit of practice.
AB  - The BTS pleural procedures audit collected data over a 2-month period in June and
      July 2011. In contrast with the 2010 audit, which focussed simply on chest drain
      insertions, data on all pleural aspirations and local anaesthetic thoracoscopy
      (LAT) was also collected. Ninety hospitals submitted data, covering a patient
      population of 33 million. Twenty-one per cent of centres ran a specialist pleural
      disease clinic, 71% had a nominated chest drain safety lead, and 20% had thoracic
      surgery on site. Additionally, one-third of centres had a physician-led LAT
      service. 

PMID- 24658343
TI  - Cation diffusion facilitators transport initiation and regulation is mediated by
      cation induced conformational changes of the cytoplasmic domain.
AB  - Cation diffusion facilitators (CDF) are part of a highly conserved protein family
      that maintains cellular divalent cation homeostasis in all domains of life. CDF's
      were shown to be involved in several human diseases, such as Type-II diabetes and
      neurodegenerative diseases. In this work, we employed a multi-disciplinary
      approach to study the activation mechanism of the CDF protein family. For this we
      used MamM, one of the main ion transporters of magnetosomes--bacterial organelles
      that enable magnetotactic bacteria to orientate along geomagnetic fields. Our
      results reveal that the cytosolic domain of MamM forms a stable dimer that
      undergoes distinct conformational changes upon divalent cation binding. MamM
      conformational change is associated with three metal binding sites that were
      identified and characterized. Altogether, our results provide a novel auto
      regulation mode of action model in which the cytosolic domain's conformational
      changes upon ligand binding allows the priming of the CDF into its transport
      mode.

PMID- 24658344
TI  - Rehabilitation Exercises for Athletes With Biceps Disorders and SLAP Lesions: A
      Continuum of Exercises With Increasing Loads on the Biceps.
AB  - BACKGROUND: Although rehabilitation exercises are recommended in the nonoperative
      and postoperative treatment of biceps-related disorders and superior labrum
      anterior-posterior (SLAP) lesions in overhead athletes, a progressive exercise
      protocol with controlled low to moderate loads on the biceps has not yet been
      described. PURPOSE: To describe a continuum of exercises with progressive low to
      moderate loads on the biceps based on electromyographic (EMG) analysis. STUDY
      DESIGN: Descriptive laboratory study. METHODS: Using surface electromyography,
      the EMG activity of 8 muscles (upper [UT], middle [MT], and lower [LT] trapezius;
      serratus anterior [SA]; anterior [AD] and posterior [PD] portions of the deltoid;
      and biceps [BB] and triceps [TB] brachii) was measured in 32 healthy participants
      performing 16 commonly described shoulder rehabilitation exercises. RESULTS: Of
      the 16 exercises, 13 (side-lying shoulder forward flexion, prone extension,
      seated rowing, serratus punch, knee push-up plus, internal and external rotation
      both in 20 degrees  and 90 degrees  of abduction, forearm supination, uppercut,
      and internal and external rotation diagonal) showed low (<20% maximal voluntary
      isometric contraction [MVIC]) EMG activity in the BB, and 3 (forward flexion in
      supination, full can, and elbow flexion in forearm supination) showed moderate
      (20%-50% MVIC) activity. None of the exercises elicited high (>50% MVIC) EMG
      activity. Based on the results, a ranking was calculated of the exercises, with
      mean EMG levels between 2.2% +/- 1.24% (during internal rotation against
      resistance in 90 degrees  of shoulder abduction) and 35.9% +/- 18.82% (during
      forward flexion in external rotation and supination) of MVIC. CONCLUSION: This
      study describes a continuum of exercises with an increasing level of EMG activity
      in the BB. Exercises targeting the trapezius resulted in less loads on the biceps
      compared with exercises for the SA. In addition, exercises with an internal
      rotation component showed low activity in the BB. In general, the exercises meant
      to target the BB showed the highest levels of activity in the BB. CLINICAL
      RELEVANCE: These results may assist the clinician in the appropriate choice of
      exercises in a graded rehabilitation program of biceps-related injuries.

PMID- 24658345
TI  - Head Trauma in Mixed Martial Arts.
AB  - BACKGROUND: Mixed martial arts (MMA) is a full combative sport with a recent
      global increase in popularity despite significant scrutiny from medical
      associations. To date, the empirical research of the risk of head injuries
      associated with this sport is limited. Youth and amateur participation is
      growing, warranting investigation into the burden and mechanism of injuries
      associated with this sport. PURPOSE: (1) To determine the incidence, risk
      factors, and characteristics of knockouts (KOs) and technical knockouts (TKOs)
      from repetitive strikes in professional MMA; and (2) to identify the mechanisms
      of head trauma and the situational factors that lead to KOs and TKOs secondary to
      repetitive strikes through video analysis. STUDY DESIGN: Descriptive epidemiology
      study. METHODS: Competition data and video records for all KOs and TKOs from
      numbered Ultimate Fighting Championship MMA events (n = 844) between 2006 to
      2012. Analyses included (1) multivariate logistic regression to investigate
      factors associated with an increased risk of sustaining a KO or TKO secondary to
      repetitive strikes and (2) video analysis of all KOs and TKOs secondary to
      repetitive strikes with descriptive statistics. RESULTS: During the study period,
      the KO rate was 6.4 per 100 athlete-exposures (AEs) (12.7% of matches), and the
      rate of TKOs secondary to repetitive strikes was 9.5 per 100 AEs (19.1% of
      matches), for a combined incidence of match-ending head trauma of 15.9 per 100
      AEs (31.9% of matches). Logistic regression identified that weight class, earlier
      time in a round, earlier round in a match, and older age were risk factors for
      both KOs and TKOs secondary to repetitive strikes. Match significance and
      previously sustained KOs or TKOs were also risk factors for KOs. Video analysis
      identified that all KOs were the result of direct impact to the head, most
      frequently a strike to the mandibular region (53.9%). The average time between
      the KO-strike and match stoppage was 3.5 seconds (range, 0-20 seconds), with
      losers sustaining an average of 2.6 additional strikes (range, 0-20 strikes) to
      the head. For TKOs secondary to strikes, in the 30-second interval immediately
      preceding match stoppage, losers sustained, on average, 18.5 strikes (range, 5-46
      strikes), with 92.3% of these being strikes to the head. CONCLUSION: Rates of KOs
      and TKOs in MMA are higher than previously reported rates in other combative and
      contact sports. Public health authorities and physicians should be cognizant of
      the rates and mechanisms of head trauma. Preventive measures to lessen the risks
      of head trauma for those who elect to participate in MMA are described.

PMID- 24658346
TI  - Shoulder activity level is not associated with the severity of symptomatic,
      atraumatic rotator cuff tears in patients electing nonoperative treatment.
AB  - BACKGROUND: Patient activity level may be an important prognostic variable
      relating to outcomes in patients with shoulder disorders. Little is known about
      the predictors of activity level in patients with shoulder disorders. HYPOTHESIS:
      Tear size and patient variables would be predictive of shoulder activity level in
      a cohort of patients who have selected initial nonoperative treatment for a
      symptomatic, atraumatic rotator cuff tear on magnetic resonance imaging (MRI).
      STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Patients with
      an atraumatic rotator cuff tear on MRI were prospectively enrolled in the
      Multicenter Orthopaedic Outcomes Network (MOON) shoulder study of nonoperative
      treatment. As part of routine data collection, these patients were asked to
      complete a previously validated shoulder activity scale. A regression analysis
      was performed to assess the association of shoulder activity level to rotator
      cuff tear characteristics, including tendon involvement and retraction, and
      patient factors such as age, sex, smoking, and occupation. RESULTS: A total of
      434 patients (220 male, 214 female) with a mean age of 62.7 years (range, 31-90
      years) completed the activity scale. Shoulder activity was not associated with
      severity of the rotator cuff tear, but it was negatively associated with age (P =
      .0001) and female sex (P = .001). The only other factor associated with shoulder
      activity level in this cohort was occupation (P = .0006). CONCLUSION: Shoulder
      activity level in patients with an atraumatic rotator cuff tear confirmed on MRI
      is not associated with severity of the tear but is affected by age, sex, and
      occupation.

PMID- 24658347
TI  - Predictors of Clinical Outcome After Acute Achilles Tendon Ruptures.
AB  - BACKGROUND: In patients with an acute Achilles tendon rupture, it has not been
      possible to determine the superiority of a single specific treatment modality
      over other treatments with respect to symptoms and function. When several
      pertinent treatment protocols are available for an injury, it is of interest to
      understand how other variables, such as age, sex, or physical activity level,
      affect outcome to better individualize the treatment. PURPOSE: To investigate
      predictors of both symptomatic and functional outcomes after an acute Achilles
      tendon rupture. STUDY DESIGN: Cohort study (Prognosis); Level of evidence, 2.
      METHODS: Ninety-three patients (79 men and 14 women; mean age, 40 years) were
      evaluated prospectively at 3, 6, and 12 months. The main outcome measures in this
      study were the Achilles tendon Total Rupture Score (ATRS) for symptoms and
      maximum heel-rise height for function. The independent variables evaluated as
      possible predictors of outcome included treatment, sex, age, body mass index
      (BMI), physical activity level, symptoms, and quality of life. RESULTS:
      Treatment, age, BMI, physical activity level, heel-rise height at 6 months, and
      the ATRS at 3 months were eligible for further analysis. Only male sex was
      included for the prediction models. The 4 different multiple linear regression
      models (predicting the ATRS at 6 and 12 months and heel-rise height at 6 and 12
      months) were significant (P < .001-.002), and the R (2) values for the models
      were 0.222 to 0.409. Surgical or nonsurgical treatment is a moderate predictor of
      symptoms and a weak predictor of heel-rise height after an acute Achilles tendon
      rupture. At the 6-month follow-up, surgical treatment was associated with a
      larger heel-rise height, but the opposite was seen at 12 months. Surgical
      treatment resulted in a lower degree of symptoms. Increasing age was a strong
      predictor of reduced heel-rise height, and an increase in age of 10 years reduced
      the expected heel-rise height by approximately 8%. A higher BMI was also a strong
      predictor of a greater degree of symptoms, and a 5-unit higher BMI predicted a
      reduction of approximately 10 points in the ATRS. CONCLUSION: The present study
      identified important possible predictors of outcome. Despite having a wide range
      of clinically relevant variables, the models had a limited ability to predict the
      final individual outcome. In general, the models appear to be better at
      predicting function than symptoms.

PMID- 24658348
TI  - Vascular xanthine oxidoreductase contributes to the antihypertensive effects of
      sodium nitrite in L-NAME hypertension.
AB  - Nitrate and nitrite have emerged as an important novel source of nitric oxide
      (NO). We have previously demonstrated that sodium nitrite is an antihypertensive
      compound that exerts antioxidant effects in experimental hypertension. These
      unpredicted antioxidant effects of nitrite raised the question whether the
      beneficial effects found were caused by its conversion to NO or simply due to
      reversal of endothelial dysfunction as a consequence of its antioxidant effects.
      Here, we evaluated the antihypertensive effects of a daily dose of sodium nitrite
      for 4 weeks in L-NAME-induced hypertension in rats. We studied the effects of
      nitrite on markers of NO bioavailability, vascular oxidative stress, and
      expression of xanthine oxidoreductase. Moreover, we tested if xanthine
      oxidoreductase inhibition could attenuate the acute hypotensive effects of sodium
      nitrite in L-NAME hypertensive rats. We found that a single pharmacological dose
      of sodium nitrite exerts antihypertensive effects in L-NAME-induced hypertension.
      While the beneficial antihypertensive properties of nitrite were associated with
      increased levels of NO metabolites, hypertension increased vascular xanthine
      oxidoreductase expression by approximately 40%, with minor increases in vascular
      superoxide production. The inhibition of xanthine oxidoreductase by oxypurinol
      attenuated the acute hypotensive effects of nitrite. Taken together, our results
      show that nitrite exerts antihypertensive effects in L-NAME hypertensive rats and
      provide evidence that xanthine oxidoreductase plays an important role in this
      antihypertensive effect.

PMID- 24658349
TI  - A multimode electromechanical parametric resonator array.
AB  - Electromechanical resonators have emerged as a versatile platform in which
      detectors with unprecedented sensitivities and quantum mechanics in a macroscopic
      context can be developed. These schemes invariably utilise a single resonator but
      increasingly the concept of an array of electromechanical resonators is promising
      a wealth of new possibilities. In spite of this, experimental realisations of
      such arrays have remained scarce due to the formidable challenges involved in
      their fabrication. In a variation to this approach, we identify 75 harmonic
      vibration modes in a single electromechanical resonator of which 7 can also be
      parametrically excited. The parametrically resonating modes exhibit vibrations
      with only 2 oscillation phases which are used to build a binary information
      array. We exploit this array to execute a mechanical byte memory, a shift
      register and a controlled-NOT gate thus vividly illustrating the availability and
      functionality of an electromechanical resonator array by simply utilising higher
      order vibration modes. 

PMID- 24658350
TI  - Transcriptionally active chromatin recruits homologous recombination at DNA
      double-strand breaks.
AB  - Although both homologous recombination (HR) and nonhomologous end joining can
      repair DNA double-strand breaks (DSBs), the mechanisms by which one of these
      pathways is chosen over the other remain unclear. Here we show that
      transcriptionally active chromatin is preferentially repaired by HR. Using
      chromatin immunoprecipitation-sequencing (ChIP-seq) to analyze repair of multiple
      DSBs induced throughout the human genome, we identify an HR-prone subset of DSBs
      that recruit the HR protein RAD51, undergo resection and rely on RAD51 for
      efficient repair. These DSBs are located in actively transcribed genes and are
      targeted to HR repair via the transcription elongation-associated mark
      trimethylated histone H3 K36. Concordantly, depletion of SETD2, the main H3 K36
      trimethyltransferase, severely impedes HR at such DSBs. Our study thereby
      demonstrates a primary role in DSB repair of the chromatin context in which a
      break occurs. 

PMID- 24658351
TI  - Structural basis for pure antagonism of integrin alphaVbeta3 by a high-affinity
      form of fibronectin.
AB  - Integrins are important therapeutic targets. However, current RGD-based anti
      integrin drugs are also partial agonists, inducing conformational changes that
      trigger potentially fatal immune reactions and paradoxical cell adhesion. Here we
      describe the first crystal structure of alphaVbeta3 bound to a physiologic
      ligand, the tenth type III RGD domain of wild-type fibronectin (wtFN10), or to a
      high-affinity mutant (hFN10) shown here to act as a pure antagonist. Comparison
      of these structures revealed a central pi-pi interaction between Trp1496 in the
      RGD-containing loop of hFN10 and Tyr122 of the beta3 subunit that blocked
      conformational changes triggered by wtFN10 and trapped hFN10-bound alphaVbeta3 in
      an inactive conformation. Removing the Trp1496 or Tyr122 side chains or
      reorienting Trp1496 away from Tyr122 converted hFN10 into a partial agonist.
      These findings offer new insights into the mechanism of integrin activation and a
      basis for the design of RGD-based pure antagonists. 

PMID- 24658352
TI  - Chemerin C9 peptide induces receptor internalization through a clathrin
      independent pathway.
AB  - AIM: The chemerin receptor CMKLR1 is one type of G protein-coupled receptors
      abundant in monocyte-derived dendritic cells and macrophages, which plays a key
      role in the entry of a subset of immunodeficiency viruses including HIV/SIV into
      lymphocytes and macrophages. The aim of this work was to investigate how CMKLR1
      was internalized and whether its internalization affected cell signaling in
      vitro. METHODS: Rat basophilic leukemia RBL-2H3 cells, HEK 293 cells, and HeLa
      cells were used. CMKLR1 internalization was visualized by confocal microscopy
      imaging or using a FACScan flow cytometer. Six potential phosphorylation sites
      (Ser337, Ser343, Thr352, Ser344, Ser347, and Ser350) in CMKLR1 were substituted
      with alanine using site-directed mutagenesis. Heterologous expression of wild
      type and mutant CMKLR1 allowed for functional characterization of endocytosis,
      Ca(2+) flux and extracellular signal-regulated kinase (ERK) phosphorylation.
      RESULTS: Chemerin and the chemerin-derived nonapeptide (C9) induced dose
      dependent loss of cell surface CMKLR1-GFP fusion protein and increased its
      intracellular accumulation in HEK 293 cells and RBL-2H3 cells stably expressing
      CMKLR1. Up to 90% of CMKLR1 was internalized after treatment with C9 (1 MUmol/L).
      By using different agents, it was demonstrated that clathrin-independent
      mechanism was involved in CMKLR1 internalization. Mutations in Ser343 for G
      protein-coupled receptor kinase phosphorylation and in Ser347 for PKC
      phosphorylation abrogated CMKLR1 internalization. Loss of CMKLR1 internalization
      partially enhanced the receptor signaling, as shown by increased Ca(2+) flux and
      a shorter latency to peak level of ERK phosphorylation. CONCLUSION: CMKLR1
      internalization occurs in a clathrin-independent manner, which negatively
      regulated the receptor-mediated Ca(2+) flux and ERK phosphorylation.

PMID- 24658356
TI  - Quantifying phytogeographical regions of Australia using geospatial turnover in
      species composition.
AB  - The largest digitized dataset of land plant distributions in Australia assembled
      to date (750,741 georeferenced herbarium records; 6,043 species) was used to
      partition the Australian continent into phytogeographical regions. We used a set
      of six widely distributed vascular plant groups and three non-vascular plant
      groups which together occur in a variety of landscapes/habitats across Australia.
      Phytogeographical regions were identified using quantitative analyses of species
      turnover, the rate of change in species composition between sites, calculated as
      Simpson's beta. We propose six major phytogeographical regions for Australia:
      Northern, Northern Desert, Eremaean, Eastern Queensland, Euronotian and South
      Western. Our new phytogeographical regions show a spatial agreement of 65% with
      respect to previously defined phytogeographical regions of Australia. We also
      confirm that these new regions are in general agreement with the biomes of
      Australia and other contemporary biogeographical classifications. To assess the
      meaningfulness of the proposed phytogeographical regions, we evaluated how they
      relate to broad scale environmental gradients. Physiographic factors such as
      geology do not have a strong correspondence with our proposed regions. Instead,
      we identified climate as the main environmental driver. The use of an
      unprecedentedly large dataset of multiple plant groups, coupled with an explicit
      quantitative analysis, makes this study novel and allows an improved historical
      bioregionalization scheme for Australian plants. Our analyses show that: (1)
      there is considerable overlap between our results and older biogeographic
      classifications; (2) phytogeographical regions based on species turnover can be a
      powerful tool to further partition the landscape into meaningful units; (3)
      further studies using phylogenetic turnover metrics are needed to test the
      taxonomic areas. 

PMID- 24658357
TI  - Strongly coupled hybrid nanostructures for selective hydrogen detection-
      understanding the role of noble metals in reducing cross-sensitivity.
AB  - Noble metal-semiconductor hybrid nanostructures can offer outperformance to gas
      sensors in terms of sensitivity and selectivity. In this work, a catalytically
      activated (CA) hydrogen sensor is realized based on strongly coupled Pt/Pd-WO3
      hybrid nanostructures constructed by a galvanic replacement participated
      solvothermal procedure. The room-temperature operation and high selectivity
      distinguish this sensor from the traditional ones. It is capable of detecting
      dozens of parts per million (ppm) hydrogen in the presence of thousands of ppm
      methane gas. An insight into the role of noble metals in reducing cross
      sensitivity is provided by comparing the sensing properties of this sensor with a
      traditional thermally activated (TA) one made from the same pristine WO3. Based
      on both experimental and density functional theory (DFT) calculation results, the
      cross-sensitivity of the TA sensor is found to have a strong dependence on the
      highest occupied molecular orbital (HOMO) level of the hydrocarbon molecules. The
      high selectivity of the CA sensor comes from the reduced impact of gas frontier
      orbitals on the charge transfer process by the nano-scaled metal-semiconductor
      (MS) interface. The methodology demonstrated in this work indicates that rational
      design of MS hybrid nanostructures can be a promising strategy for highly
      selective gas sensing applications. 

PMID- 24658355
TI  - Functional analysis of MKP-1 and MKP-2 in breast cancer tamoxifen sensitivity.
AB  - Increased activation of ERK signaling has been reported in breast cancer models
      of acquired tamoxifen resistance. Here, we examined the expression of Mitogen
      Activated Protein Kinase Phosphatases (MKPs) 1 and 2 following tamoxifen
      treatment and the effects of MKP-1/MKP-2 overexpression on tamoxifen sensitivity.
      Treatment of MCF7 breast cancer cells with tamoxifen increased MKP-2, but not MKP
      1, protein levels. Overexpression of MKP-1 or MKP-2 inhibited estrogen-induced
      MCF7 cell proliferation compared to vector controls. MCF7-MKP-2 cells displayed
      significantly increased sensitivity to tamoxifen as compared to vector control or
      MCF7-MKP-1 cells. MKP-1 or MKP-2 overexpression eliminated ERK1/2
      phosphorylation, suggesting that decreases in estrogen-induced proliferation of
      MKP-1 and MKP-2 overexpressing cells are due to ERK1/2 dephosphorylation. JNK1/2
      activation was not detectable in any of these cells. These data suggest that
      tamoxifen-induced death of these cells is not dependent upon JNK signaling, but
      rather that ERK is the major MAPK driving their proliferation. MCF7-TAMR cells
      express higher levels of MKP-2 mRNA and protein than MCF7 cells. MKP-2 and
      phospho-ERK1/2 proteins are constitutively expressed in MCF7-TAMR cells, and
      activated JNK1/2 is not detectable. These data suggest that MKP-2 rather than MKP
      1 is tamoxifen-regulated and that the elevated expression of MKP-2 in MCF7-TAMR
      cells potentially functions to restore tamoxifen sensitivity. 

PMID- 24658358
TI  - Long-term reliability of Al2O3 and Parylene C bilayer encapsulated Utah electrode
      array based neural interfaces for chronic implantation.
AB  - OBJECTIVE: We focus on improving the long-term stability and functionality of
      neural interfaces for chronic implantation by using bilayer encapsulation.
      APPROACH: We evaluated the long-term reliability of Utah electrode array (UEA)
      based neural interfaces encapsulated by 52 nm of atomic layer deposited Al2O3 and
      6 um of Parylene C bilayer, and compared these to devices with the baseline
      Parylene-only encapsulation. Three variants of arrays including wired, wireless,
      and active UEAs were used to evaluate this bilayer encapsulation scheme, and were
      immersed in phosphate buffered saline (PBS) at 57  degrees C for accelerated
      lifetime testing. MAIN RESULTS: The median tip impedance of the bilayer
      encapsulated wired UEAs increased from 60 to 160 kOmega during the 960 days of
      equivalent soak testing at 37  degrees C, the opposite trend to that typically
      observed for Parylene encapsulated devices. The loss of the iridium oxide tip
      metallization and etching of the silicon tip in PBS solution contributed to the
      increase of impedance. The lifetime of fully integrated wireless UEAs was also
      tested using accelerated lifetime measurement techniques. The bilayer coated
      devices had stable power-up frequencies at ~910 MHz and constant radio-frequency
      signal strength of -50 dBm during up to 1044 days (still under testing) of
      equivalent soaking time at 37  degrees C. This is a significant improvement over
      the lifetime of ~100 days achieved with Parylene-only encapsulation at 37 
      degrees C. The preliminary samples of bilayer coated active UEAs with a flip-chip
      bonded ASIC chip had a steady current draw of ~3 mA during 228 days of soak
      testing at 37  degrees C. An increase in the current draw has been consistently
      correlated to device failures, so is a sensitive metric for their lifetime.
      SIGNIFICANCE: The trends of increasing electrode impedance of wired devices and
      performance stability of wireless and active devices support the significantly
      greater encapsulation performance of this bilayer encapsulation compared with
      Parylene-only encapsulation. The bilayer encapsulation should significantly
      improve the in vivo lifetime of neural interfaces for chronic implantation.

PMID- 24658359
TI  - Verapamil protects against cartilage degradation in osteoarthritis by inhibiting
      Wnt/beta-catenin signaling.
AB  - In past years, the canonical Wnt/beta-catenin signaling pathway has emerged as a
      critical regulator of cartilage development and homeostasis. FRZB, a soluble
      antagonist of Wnt signaling, has been studied in osteoarthritis (OA) animal
      models and OA patients as a modulator of Wnt signaling. We screened for FDA
      approved drugs that induce FRZB expression and suppress Wnt/beta-catenin
      signaling. We found that verapamil, a widely prescribed L-type calcium channel
      blocker, elevated FRZB expression and suppressed Wnt/beta-catenin signaling in
      human OA chondrocytes. Expression and nuclear translocation of beta-catenin was
      attenuated by verapamil in OA chondrocytes. Lack of the verapamil effects in LiCl
      treated and FRZB-downregulated OA chondrocytes also suggested that verpamil
      suppressed Wnt signaling by inducing FRZB. Verapamil enhanced gene expressions of
      chondrogenic markers of ACAN encoding aggrecan, COL2A1 encoding collagen type II
      alpha1, and SOX9, and suppressed Wnt-responsive AXIN2 and MMP3 in human OA
      chondrocytes. Verapamil ameliorated Wnt3A-induced proteoglycan loss in
      chondrogenically differentiated ATDC5 cells. Verapamil inhibited hypertrophic
      differentiation of chondrocytes in the explant culture of mouse tibiae.
      Intraarticular injection of verapamil inhibited OA progression as well as nuclear
      localizations of beta-catenin in a rat OA model. We propose that verapamil holds
      promise as a potent therapeutic agent for OA by upregulating FRZB and
      subsequently downregulating Wnt/beta-catenin signaling. 

PMID- 24658360
TI  - Community structure and activity of a highly dynamic and nutrient-limited
      hypersaline microbial mat in Um Alhool Sabkha, Qatar.
AB  - The Um Alhool area in Qatar is a dynamic evaporative ecosystem that receives
      seawater from below as it is surrounded by sand dunes. We investigated the
      chemical composition, the microbial activity and biodiversity of the four main
      layers (L1-L4) in the photosynthetic mats. Chlorophyll a (Chl a) concentration
      and distribution (measured by HPLC and hyperspectral imaging, respectively), the
      phycocyanin distribution (scanned with hyperspectral imaging), oxygenic
      photosynthesis (determined by microsensor), and the abundance of photosynthetic
      microorganisms (from 16S and 18S rRNA sequencing) decreased with depth in the
      euphotic layer (L1). Incident irradiance exponentially attenuated in the same
      zone reaching 1% at 1.7-mm depth. Proteobacteria dominated all layers of the mat
      (24%-42% of the identified bacteria). Anoxygenic photosynthetic bacteria
      (dominated by Chloroflexus) were most abundant in the third red layer of the mat
      (L3), evidenced by the spectral signature of Bacteriochlorophyll as well as by
      sequencing. The deep, black layer (L4) was dominated by sulfate reducing bacteria
      belonging to the Deltaproteobacteria, which were responsible for high sulfate
      reduction rates (measured using 35S tracer). Members of Halobacteria were the
      dominant Archaea in all layers of the mat (92%-97%), whereas Nematodes were the
      main Eukaryotes (up to 87%). Primary productivity rates of Um Alhool mat were
      similar to those of other hypersaline microbial mats. However, sulfate reduction
      rates were relatively low, indicating that oxygenic respiration contributes more
      to organic material degradation than sulfate reduction, because of bioturbation.
      Although Um Alhool hypersaline mat is a nutrient-limited ecosystem, it is
      interestingly dynamic and phylogenetically highly diverse. All its components
      work in a highly efficient and synchronized way to compensate for the lack of
      nutrient supply provided during regular inundation periods. 

PMID- 24658361
TI  - Protein catabolism and high lipid metabolism associated with long-distance
      exercise are revealed by plasma NMR metabolomics in endurance horses.
AB  - During long distance endurance races, horses undergo high physiological and
      metabolic stresses. The adaptation processes involve the modulation of the
      energetic pathways in order to meet the energy demand. The aims were to evaluate
      the effects of long endurance exercise on the plasma metabolomic profiles and to
      investigate the relationships with the individual horse performances. The
      metabolomic profiles of the horses were analyzed using the non-dedicated
      methodology, NMR spectroscopy and statistical multivariate analysis. The
      advantage of this method is to investigate several metabolomic pathways at the
      same time in a single sample. The plasmas were obtained before exercise (BE) and
      post exercise (PE) from 69 horses competing in three endurance races at national
      level (130-160 km). Biochemical assays were also performed on the samples taken
      at PE. The proton NMR spectra were compared using the supervised orthogonal
      projection on latent structure method according to several factors. Among these
      factors, the race location was not significant whereas the effect of the race
      exercise (sample BE vs PE of same horse) was highly discriminating. This result
      was confirmed by the projection of unpaired samples (only BE or PE sample of
      different horses). The metabolomic profiles proved that protein, energetic and
      lipid metabolisms as well as glycoproteins content are highly affected by the
      long endurance exercise. The BE samples from finisher horses could be
      discriminated according to the racing speed based on their metabolomic lipid
      content. The PE samples could be discriminated according to the horse ranking
      position at the end of the race with lactate as unique correlated metabolite. As
      a conclusion, the metabolomic profiles of plasmas taken before and after the race
      provided a better understanding of the high energy demand and protein catabolism
      pathway that could expose the horses to metabolic disorders. 

PMID- 24658362
TI  - Treatment of rotavirus-associated diarrhea using enteral immunoglobulins for
      pediatric stem cell transplant patients.
AB  - Diarrhea is a common complication associated with allogeneic and autologous stem
      cell transplant patients. One potential cause of viral diarrhea is rotavirus
      gastroenteritis. This study represents a single-center experience of using
      multiple daily doses of enteral immunoglobulins in four pediatric hematopoietic
      stem cell transplant patients with confirmed rotavirus infections. Four courses
      of enteral immunoglobulin administration were included for analysis. Clinical
      characteristics recorded included duration of diarrhea symptoms, frequency of
      bowel movements, and consistency of stool. Four single courses of enteral
      immunoglobulins in four patients were included for analysis. Patient age range
      was from 10 months to 14 years. Three out of four courses observed displayed an
      improvement in diarrhea frequency and/or stool consistency. Median time from
      therapy initiation to symptom improvement was three days. At a median 22-month
      follow-up, one patient was diagnosed with gastrointestinal graft-versus-host
      disease. The time to rotavirus symptom resolution was decreased, compared to
      historical controls, and improvement in stool frequency and consistency was
      observed in three of four courses. One case of gastrointestinal graft-versus-host
      disease was observed after nearly two years of follow-up. Enteral administration
      of immunoglobulins may represent a valid clinical option for hematopoietic stem
      cell transplant patients with rotavirus diarrhea. 

PMID- 24658364
TI  - Measuring HIV stigma at the family level: psychometric assessment of the Chinese
      Courtesy Stigma Scales (CCSSs).
AB  - Courtesy stigma is the stigmatization a person perceives or experiences due to
      their association with a stigmatized individual or group. Most HIV-related stigma
      scales have been developed for people living with HIV/AIDS (PLWHAs), but not for
      their HIV-uninfected family members. To date, few measurement scales have been
      designed to measure the degree of stigma among both PLWHAs and their HIV
      uninfected family members at the family level. We developed a set of courtesy
      stigma scales and estimated their reliability and validity from 256 PLWHAs and
      256 of their HIV-uninfected family members. Exploratory and confirmatory factor
      analyses were performed in two independent samples: a development sample (N =
      216) and a validation sample (N = 296), respectively. Two factors ("public
      stigma" and "self-perceived stigma") had high internal consistency reliability
      (Cronbach's alpha coefficient between 0.83-0.90) and good construct validity
      (standardized factor loading range: 0.37-0.95) in both samples. These findings
      document that the newly developed brief instrument is a psychometrically sound
      measure of HIV-related stigma among both PLWHAs and their HIV-uninfected family
      members. 

PMID- 24658363
TI  - Evidence of a novel mechanism for partial gamma-secretase inhibition induced
      paradoxical increase in secreted amyloid beta protein.
AB  - BACE1 (beta-secretase) and alpha-secretase cleave the Alzheimer's amyloid beta
      protein (Abeta) precursor (APP) to C-terminal fragments of 99 aa (CTFbeta) and 83
      aa (CTFalpha), respectively, which are further cleaved by gamma-secretase to
      eventually secrete Abeta and Aalpha (a.k.a. P3) that terminate predominantly at
      residues 40 and 42. A number of gamma-secretase inhibitors (GSIs), such as N-[N
      (3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), have
      been developed with the goal of reducing Abeta to treat Alzheimer's disease (AD).
      Although most studies show that DAPT inhibits Abeta in a dose-dependent manner
      several studies have also detected a biphasic effect with an unexpected increase
      at low doses of DAPT in cell cultures, animal models and clinical trials. In this
      article, we confirm the increase in Abeta40 and Abeta42 in SH-SY5Y human
      neuroblastoma cells treated with low doses of DAPT and identify one of the
      mechanisms for this paradox. We studied the pathway by first demonstrating that
      stimulation of Abeta, a product of gamma-secretase, was accompanied by a parallel
      increase of its substrate CTFbeta, thereby demonstrating that the inhibitor was
      not anomalously stimulating enzyme activity at low levels. Secondly, we have
      demonstrated that inhibition of an Abeta degrading activity, endothelin
      converting enzyme (ECE), yielded more Abeta, but abolished the DAPT-induced
      stimulation. Finally, we have demonstrated that Aalpha, which is generated in the
      secretory pathway before endocytosis, is not subject to the DAPT-mediated
      stimulation. We therefore conclude that impairment of gamma-secretase can
      paradoxically increase Abeta by transiently skirting Abeta degradation in the
      endosome. This study adds to the growing body of literature suggesting that
      preserving gamma-secretase activity, rather than inhibiting it, is important for
      prevention of neurodegeneration. 

PMID- 24658365
TI  - Novel metallo-therapeutics of the NSAID naproxen. Interaction with intracellular
      components that leads the cells to apoptosis.
AB  - Two new mixed ligand-silver(I) complexes of the anti-inflammatory drug naproxen
      (naprH) and triphenylphosphine (tpp) or tri(p-tolyl)phosphine (tptp) of formulae
      {[Ag(tpp)3(napr)](H2O)} (1) and [Ag(tptp)2(napr)] (2) have been synthesized and
      characterized by m.p., vibrational spectroscopy (mid-FT-IR), Raman, (1)H-NMR, UV
      Vis, ESI-MS spectroscopic techniques and X-ray crystallography. The complexes
      show high photo-sensitivity to UVC light. Photolysis of 1-2 was studied and the
      results showed monotonic degradation of the complexes with simultaneous
      triarylphosphine oxide formation. The complexes 1-2 were tested for their
      antiproliferative activity against human breast adenocarcinoma (MCF-7) cells.
      Complexes 1-2 were more active than cisplatin against cells. UVC light increases
      the effectiveness of complexes 1-2 on MCF-7 cells by 13% and 38% respectively.
      Due to the morphology of the MCF-7 cells, which were incubated with the complexes
      1-2, the cell death was ascribed to apoptosis. Electrophoresis to genomic DNA of
      MCF-7 cells confirmed the apoptosis through DNA fragmentation. The binding
      affinity of 1-2 towards the intracellular molecules CT-DNA and lipoxygenase (LOX)
      was studied for the evaluation of the mechanism of cell death. Thus, the binding
      constants (K(b)) of 1-2 towards CT-DNA calculated by UV-Vis spectra are 32.8 +/-
      8.5 * 10(4) (1) and 4.7 +/- 1.8 * 10(4) (2) M(-1), respectively. Changes in
      fluorescent emission light of ethidium bromide (EB) in the presence of DNA
      suggest intercalation or electrostatic interactions into DNA of both complexes 1
      2 in the minor groove. The corresponding apparent binding constants (K(app)) of 1
      2 towards CT-DNA calculated through fluorescence spectra are 2.9 +/- 0.3 * 10(4)
      (1) and 1.6 +/- 0.4 * 10(4) (2) M(-1) respectively. Docking studies on DNA
      complexes interactions show the binding of 1 in the major groove and the
      corresponding one of 2 in the minor one. Moreover, the influence of complexes 1-2
      on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the
      enzyme lipoxygenase (LOX) was kinetically and theoretically studied. Only 1
      inhibits lipoxygenase activity (IC50 = 5.1 (1), >30 (2) MUM).

PMID- 24658366
TI  - Supramolecular gel from folic acid with multiple responsiveness, rapid self
      recovery and orthogonal self-assemblies.
AB  - Through a good/poor solvent strategy, native folic acid (FA) which behaves as a
      super-gelator in DMSO-water system can be successfully employed to construct
      supramolecular gels. The system exhibited morphological evolution with the
      increase of FA concentration; various phases such as vesicles, fiber/vesicles,
      fiber/nanoparticles, nanoparticles were probed. In the self-assembly process, l
      glutamic acid moiety induced the formation of helical 1-dimensional (1-D) fibers
      which further self-assembled into a gel. Stimuli like heat, stress, pH and light
      which affect the molecular structure of FA or solubility in the mixed solvents
      had a pronounced influence on the properties of the gels, such as mechanical
      properties or bulk phases. A time-dependent oscillatory stress scan indicated
      that the supramolecular gel had a self-healing property. Without tedious
      modification routes and addition of alkali metal ions, native FA which served as
      an efficient building block and super-gelator to build up multi-responsive and
      self-recovery material was investigated for the first time. 

PMID- 24658367
TI  - Client-centred therapy in multiple sclerosis: more intensive diagnostic
      evaluation and less intensive treatment.
AB  - OBJECTIVE: Despite beneficial effects on communication and process measures,
      client-centred practice has been shown to result in poor functional outcomes. To
      examine a potential explanation for poor functional outcomes, this paper aims to
      assess whether in client-centred therapy more time is spent on diagnostic
      consultation and less time on actual treatment compared to usual care. METHOD: A
      multicentre cluster randomised controlled trial was performed. Thirteen hospitals
      and rehabilitation centres, 29 therapists and 269 outpatients with multiple
      sclerosis participated. Measurements included an inventory of diagnostic and
      treatment goals, the number of sessions, therapy duration and therapy intensity.
      RESULTS: In client-centred therapy, more sessions were used for diagnostic
      consultation (10.9% points difference, p = 0.030); the time needed to formulate
      the first treatment goal was longer (11.4 days difference, p = 0.041); there was
      a tendency towards more goals directed to diagnostic issues (0.69 goals
      difference, p = 0.056), spending more hours on indirect issues (1.16 h
      difference, p = 0.051) and towards a longer total therapy period (1.56 months
      difference, p = 0.058) than in usual care. CONCLUSION: Client-centred therapy
      resulted in more intensive diagnostic evaluation and less intensive treatment.
      This suggests that client-centred therapy should be adjusted towards a more
      proportional distribution of time devoted to diagnostic evaluation versus actual
      treatment.

PMID- 24658368
TI  - Impact of flexible body surface coil and patient table on PET quantification and
      image quality in integrated PET/MR.
AB  - AIM: The surface coils of the Biograph mMR integrated PET/MR system were
      optimised for PET, but are otherwise unaccounted for. The patient table is still
      more massive than those of PET/CT devices. The goal was to assess those hardware
      effects on quantification, count statistics, image quality and scan time both
      with phantoms and in patients and to investigate their clinical relevance.
      PATIENTS, MATERIAL, METHODS: PET phantom data were acquired with and without the
      patient table. Image noise was expressed as relative standard deviation and
      compared to a state-of-the-art PET/CT scanner. Protocols of the phantom/patient
      study regarding the surface coils were similar. Thoraces/abdomens of 11 patients
      were scanned with and without a coil (1 BP, 4 min). Mean uptake and standard
      deviation in a cubical VOI were derived and expressed as SUV. RESULTS: The
      patient table reduced the number of true coincidences (trues) by 19% (PET/MR) and
      by 11% (PET/CT). The scan duration for the mMR had to be increased by
      approximately 30% to achieve a noise level comparable to that of the PET/CT.
      Decreased SUVs with coil observed in the phantom were confirmed by the patient
      study. By removing the coil, the mean liver SUV increased by (6 +/- 2)%. With (+3
      +/- 14)%, the average change was similar in lesions, but exceeded 20% in almost
      one fifth of them. The number of trues grew by (6 +/- 1)% for the patients and by
      7% for the phantom. CONCLUSION: Due to the additional attenuation caused by MR
      hardware, PET scan durations would have to be increased compared to current
      PET/CTs to provide similar image noise levels. The effect of the coils is mostly
      in the order of statistical fluctuations. In tumour lesions, it is more
      pronounced and shows a larger variability. Therefore, coils should be included in
      the attenuation correction to ensure accurate quantification and thus
      comparability across PET/MR and PET/CT scanners and within patient populations.

PMID- 24658369
TI  - Basal level of FANCD2 monoubiquitination is required for the maintenance of a
      sufficient number of licensed-replication origins to fire at a normal rate.
AB  - Normal DNA replication starts following the stepwise recruitment of replication
      initiators to assemble Mini-chromosome Maintenance (MCM) 2-7 protein complexes at
      an adequate amount of DNA replication origins. Under normal conditions, the
      monoubiquitination of Fanconi Anemia (FA) group D2 protein (FANCD2) occurs in
      each S-phase of cell cycle, which is the basal level of FANCD2
      monoubiquitination. However, little is known regarding the roles of this basal
      level of monoubiquitinated FANCD2. Here we show that monoubiquitinated FANCD2 in
      each S-phase of normal cell cycle is essential for replication origins to fire at
      a normal rate. We found that the basal level of the monoubiquitinated FANCD2 can
      interact with replication origins as well as mini-chromosome maintenance protein
      3 (MCM3) in an S-phase specific manner to secure an enough number of the licensed
      origins to fire. Non-monoubiquitinated FANCD2 or mutant MCM3 lacking AA 477-480
      responsible for interacting with FANCD2 can lead to an insufficient amount of
      licensed origins to fire and, thereby, enlarged intervals between the fired
      origins. Our results demonstrate that the monoubiquitinated FANCD2 in each S
      phase of normal cell cycle is required to maintain an enough number of licensed
      origins to initiate the normal DNA replication. This finding is the first to
      provide insights into how FANCD2 functions under normal condition of cell cycle
      to maintain genome stability, as well as resulting implications in the strategic
      improvement for the fight against human cancer. 

PMID- 24658370
TI  - Methane formation and consumption processes in Xiangxi Bay of the Three Gorges
      Reservoir.
AB  - Indoor simulation experiment was carried out to evaluate the formation and
      consumption rates of methane (CH4) in Xiangxi Bay of the Three Gorges Reservoir
      (TGR), China. The results show that both the CH4 formation and consumption rates
      were significantly positively correlated with temperature. CH4 efflux decreased
      with rising temperature due to its potential increasing oxidation rate. CH4
      oxidation in surface sediments accounted for 51.8% of the total production and it
      even reached to 77.4% at 35 degrees C. The methane oxidation rate in water column
      ranged from 1.26 to 4.65 mg/(m(2)h), of which the average and greatest rate
      accounted for 46.7% and 73.9% of CH4 production respectively under the condition
      of 30 m water column and 35 degrees C. The methane oxidation may increase by
      41.04 mg/(m(2)h) under average water level of TGR (160 m), and most methane
      resulted from sediments can be oxidized in the water column.

PMID- 24658371
TI  - ProHNPs are specific markers of normal myelopoiesis.
AB  - Pro human neutrophil peptides (proHNP)s are proforms of alpha-defensins produced
      by precursors of human neutrophils. They are secreted to bone marrow plasma in
      large amounts by myelocytes. We hypothesized that the plasma concentration of
      proHNPs might serve as a specific marker of myelopoietic activity, heralding the
      onset of normal myelopoiesis before reappearance of neutrophils, in the setting
      of bone marrow regeneration. To investigate this, plasma levels of proHNPs were
      measured by enzyme-linked immunosorbent assay in blood samples collected from
      patients undergoing allogeneic (n=11) or autologous (n=16) stem cell
      transplantations (SCTs) and patients receiving chemotherapy for acute leukemia
      (n=14). To compare proHNPs with previously suggested myeloid markers,
      myeloperoxidase (MPO), lysozyme and neutrophil gelatinase-associated lipocalin
      (NGAL) were also assayed. In all but one patient, chemotherapy led to the
      complete disappearance of ProHNPs from plasma. It reappeared in plasma on average
      6.3 days before reappearance of neutrophils in the allogeneic setting, whereas
      this was reduced to an average of 2.8 days in the autologous SCT patients who
      received granulocyte colony-stimulating factor. Patients with acute myeloid
      leukemia (n=19) had significantly lower levels of plasma proHNPs than healthy
      controls, indicating that proHNPs are not produced by leukemic blasts. We
      conclude that plasma concentration of proHNPs is a clinically useful marker of
      normal myelopoiesis. 

PMID- 24658372
TI  - CD123 targeting oncolytic adenoviruses suppress acute myeloid leukemia cell
      proliferation in vitro and in vivo.
AB  - We report here a novel strategy to redirect oncolytic adenoviruses to CD123 by
      carry a soluble coxsackie-adenovirus receptor (sCAR)-IL3 expression cassette in
      the viral genome to form Ad.IL3, which sustainably infected acute myeloid
      leukemia (AML) cells through CD123. Ad.IL3 was further engineered to harbor gene
      encoding manganese superoxide dismutase (MnSOD) or mannose-binding plant lectin
      Pinellia pedatisecta agglutinin (PPA), forming Ad.IL3-MnSOD and Ad.IL3-PPA. As
      compared with Ad.IL3 or Ad.sp-E1A control, Ad.IL3-MnSOD and Ad.IL3-PPA
      significantly suppressed in vitro proliferation of HL60 and KG-1 cells. Elevated
      apoptosis was detected in HL60 and KG-1 cells treated with either Ad.IL3-MnSOD or
      Ad.IL3-PPA. The caspase-9-caspase-7 pathway was determined to be activated by
      Ad.IL3-MnSOD as well as by Ad.IL3-PPA in HL60 cells. In an HL60/Luc xenograft
      nonobese diabetic/severe-combined immunodeficiency mice model, Ad.IL3-MnSOD and
      Ad.IL3-PPA suppressed cancer cell growth as compared with Ad.IL3. A significant
      difference of cancer cell burden was detected between Ad.IL3 and Ad.IL3-PPA
      groups at day 9 after treatment. Furthermore, Ad.IL3-MnSOD significantly
      prolonged mouse survival as compared with Ad.sp-E1A. These findings demonstrated
      that Ad.IL3-gene could serve as a novel agent for AML therapy. Harboring sCAR
      ligand expression cassette in the viral genome may provide a universal method to
      redirect oncolytic adenoviruses to various membrane receptors on cancer cells
      resisting serotype 5 adenovirus infection. 

PMID- 24658373
TI  - Acute promyelocytic leukemias share cooperative mutations with other myeloid
      leukemia subgroups.

PMID- 24658374
TI  - Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling
      through ALK2 but is inhibited by endoglin.
AB  - Multiple myeloma is a malignancy of plasma cells predominantly located in the
      bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in
      myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has
      been found in human serum at concentrations that inhibit cancer cell growth in
      vitro. We here show that the level of BMP-9 in serum was elevated in myeloma
      patients (median 176 pg/ml, range 8-809) compared with healthy controls (median
      110 pg/ml, range 8-359). BMP-9 was also present in the bone marrow and was able
      to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling
      through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC
      downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105)
      or soluble endoglin present in the bone marrow microenvironment, suggesting a
      mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9
      in multiple myeloma. 

PMID- 24658375
TI  - All-trans retinoic acid-induced inflammatory myositis in a patient  with acute
      promyelocytic leukemia.
AB  - All-trans retinoic acid (ATRA), a component of standard therapy for acute
      promyelocytic leukemia (APL), is associated with potentially serious but
      treatable adverse effects involving numerous organ systems, including rare
      skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in
      children have been reported, and none in the radiology literature. We present
      such a case in a 15-year-old boy with APL, where recognition of imaging findings
      played a crucial role in making the diagnosis and facilitated prompt, effective
      treatment.

PMID- 24658377
TI  - Cutaneous lymphomas: an update. Part 2: B-cell lymphomas and related conditions.
AB  - : Primary cutaneous B-cell lymphomas (PCBCL) are the second most common form of
      primary cutaneous lymphomas and account for approximately 25%-30% of all primary
      cutaneous lymphomas. Both forms of low-grade malignant PCBCL, primary cutaneous
      follicle center lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma of
      mucosa-associated lymphoid tissue-type (MALT lymphoma) (PCMZL) represent the vast
      majority of PCBCL and show an indolent slowly progressive course and an excellent
      prognosis despite a high recurrence rate. Genetic analysis indicates that PCMZL
      differ from other forms of extranodal MALT lymphomas. The more common class
      switched and the non-class-switched form of PCMZL can be distinguished as two
      distinctive subsets that differ in the cellular composition, IgM expression, and
      biological behavior with extracutaneous involvement found in the non-class
      switched form. Recently, unusual clinical and histological forms of PCMZL and
      PCFCL manifesting with miliary or agminated lesions have been described that are
      diagnostically challenging. In contrast to PCMZL and PCFCL, primary cutaneous
      diffuse large B-cell lymphoma, leg type, and other rare forms of large B-cell
      lymphomas such as intravascular large B-cell lymphoma have an unfavorable
      prognosis. There is an emerging group of Epstein-Barr virus (EBV)-driven B-cell
      lymphoproliferations including posttransplant lymphoproliferative disorders and
      mucocutaneous ulcer occurring in immunocompromised patients and EBV-associated
      diffuse large B-cell lymphoma of the elderly arising in the setting of senescence
      linked immunodeficiency. This review reports on recent findings expanding the
      spectrum of clinicopathological features, differential diagnostic aspects, and
      the pathogenesis of PCBCL and discusses the group of EBV-associated B-cell
      lymphoproliferations involving the skin. 

PMID- 24658376
TI  - Predicting the severity and prognosis of trismus after intensity-modulated
      radiation therapy for oral cancer patients by magnetic resonance imaging.
AB  - To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome
      for post-operative oral cavity cancer patients who received adjuvant intensity
      modulated radiation therapy (IMRT), 22 patients with oral cancer treated with
      IMRT were studied over a two-year period. Signal abnormality scores (SA scores)
      were computed from Likert-type ratings of the abnormalities of nine masticator
      structures and compared with the Mann-Whitney U-test and Kruskal-Wallis one-way
      ANOVA test between groups. Seventeen patients (77.3%) experienced different
      degrees of trismus during the two-year follow-up period. The SA score correlated
      with the trismus grade (r = 0.52, p<0.005). Patients having progressive trismus
      had higher mean doses of radiation to multiple structures, including the
      masticator and lateral pterygoid muscles, and the parotid gland (p<0.05). In
      addition, this group also had higher SA-masticator muscle dose product at 6
      months and SA scores at 12 months (p<0.05). At the optimum cut-off points of 0.38
      for the propensity score, the sensitivity was 100% and the specificity was 93%
      for predicting the prognosis of the trismus patients. The SA score, as determined
      using MRI, can reflect the radiation injury and correlate to trismus severity.
      Together with the radiation dose, it could serve as a useful biomarker to predict
      the outcome and guide the management of trismus following radiation therapy. 

PMID- 24658378
TI  - Immunohistochemistry for histone h3 lysine 9 methyltransferase and demethylase
      proteins in human melanomas.
AB  - Methylation and demethylation of histone H3 lysine 9 (H3K9) play a role in the
      transcriptional regulation of several cancer-related genes and are closely
      associated with malignant tumor behavior. A novel study has recently demonstrated
      that SETDB1, a member of the H3K9 methyltransferases, accelerates tumor formation
      significantly in a zebrafish melanoma model. However, the expression of H3K9
      methyltransferases including SETDB1 and demethylases has not been systematically
      examined in samples of human melanoma. Here, we used immunohistochemistry to
      examine the expression of the H3K9 methyltransferases, EHMT2 and SETDB1, and a
      H3K9 demethylase, LSD1, in 67 patients with melanoma. Overexpression of EHMT2,
      SETDB1, and LSD1 was observed in 14 (21%), 38 (57%), and 53 (79%) of the 67
      patients, respectively. A significant relationship was observed between
      overexpression of EHMT2 or SETDB1 and aggressive tumor behavior such as lymph
      node metastasis and/or distant metastasis (P < 0.05), whereas no significant
      relationship was evident for LSD1 immunoreactivity. Univariate log-rank tests
      demonstrated that patients with melanoma overexpressing EHMT2 had a poorer
      outcome (P < 0.001), whereas overexpression of SETDB1 or LSD1 had no prognostic
      impact. These results suggest that overexpression of EHMT2 might be a prognostic
      marker in patients with melanoma.

PMID- 24658379
TI  - A verrucous and ulcerated lesion of the leg: challenge. Deep mycosis by
      Trichophyton species.

PMID- 24658381
TI  - Cutaneous Rosai-Dorfman disease following a classical Hodgkin lymphoma, nodular
      sclerosis subtype.

PMID- 24658382
TI  - The epidemic characteristics and changing trend of hemorrhagic fever with renal
      syndrome in Hubei Province, China.
AB  - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is caused by different
      hantaviruses within the Bunyaviridae family. HFRS is a fulminant, infectious
      disease that occurs worldwide and is endemic in all 31 provinces of China. Since
      the first HFRS case in Hubei Province was reported in 1957, the disease has
      spread across the province and Hubei has become one of the seriously affected
      areas in China with the greatest number of reported HFRS cases in the 1980's.
      However, the epidemic characteristics of HFRS in Hubei are still not entirely
      clear and long-term, systematic investigations of this epidemic area have been
      very limited. METHODS: The spatiotemporal distribution of HFRS was investigated
      using data spanning the years 1980 to 2009. The annual HFRS incidence, fatality
      rate and seasonal incidence between 1980 and 2009 were calculated and plotted.
      GIS-based spatial analyses were conducted to detect the spatial distribution and
      seasonal pattern of HFRS. A spatial statistical analysis, using Kulldorff's
      spatial scan statistic, was performed to identify clustering of HFRS. RESULTS: A
      total of 104,467 HFRS cases were reported in Hubei Province between 1980 and
      2009. Incidence of and mortality due to HFRS declined after the outbreak in 1980s
      and HFRS cases have been sporadic in recent years. The locations and scale of
      disease clusters have changed during the three decades. The seasonal epidemic
      pattern of HFRS was characterized by the shift from the unimodal type
      (autumn/winter peak) to the bimodal type. CONCLUSIONS: Socioeconomic development
      has great influence on the transmission of hantaviruses to humans and new
      epidemic characteristics have emerged in Hubei Province. It is necessary to
      reinforce preventative measures against HFRS according to the newly-presented
      seasonal variation and to intensify these efforts especially in the urban areas
      of Hubei Province.

PMID- 24658383
TI  - Quantification and kinetic analysis of Grb2-EGFR interaction on micro-patterned
      surfaces for the characterization of EGFR-modulating substances.
AB  - The identification of the epidermal growth factor receptor (EGFR) as an oncogene
      has led to the development of several anticancer therapeutics directed against
      this receptor tyrosine kinase. However, drug resistance and low efficacy remain a
      severe challenge, and have led to a demand for novel systems for an efficient
      identification and characterization of new substances. Here we report on a
      technique which combines micro-patterned surfaces and total internal reflection
      fluorescence (TIRF) microscopy (MU-patterning assay) for the quantitative
      analysis of EGFR activity. It does not simply measure the phosphorylation of the
      receptor, but instead quantifies the interaction of the key signal transmitting
      protein Grb2 (growth factor receptor-bound protein 2) with the EGFR in a live
      cell context. It was possible to demonstrate an EGF dependent recruitment of Grb2
      to the EGFR, which was significantly inhibited in the presence of clinically
      tested EGFR inhibitors, including small tyrosine kinase inhibitors and monoclonal
      antibodies targeting the EGF binding site. Importantly, in addition to its
      potential use as a screening tool, our experimental setup offers the possibility
      to provide insight into the molecular mechanisms of bait-prey interaction.
      Recruitment of the EGFR together with Grb2 to clathrin coated pits (CCPs) was
      found to be a key feature in our assay. Application of bleaching experiments
      enabled calculation of the Grb2 exchange rate, which significantly changed upon
      stimulation or the presence of EGFR activity inhibiting drugs. 

PMID- 24658384
TI  - SIFamide and SIFamide receptor defines a novel neuropeptide signaling to promote
      sleep in Drosophila.
AB  - SIFamide receptor (SIFR) is a Drosophila G protein-coupled receptor for the
      neuropeptide SIFamide (SIFa). Although the sequence and spatial expression of
      SIFa are evolutionarily conserved among insect species, the physiological
      function of SIFa/SIFR signaling remains elusive. Here, we provide genetic
      evidence that SIFa and SIFR promote sleep in Drosophila. Either genetic ablation
      of SIFa-expressing neurons in the pars intercerebralis (PI) or pan-neuronal
      depletion of SIFa expression shortened baseline sleep and reduced sleep-bout
      length, suggesting that it caused sleep fragmentation. Consistently, RNA
      interference- mediated knockdown of SIFR expression caused short sleep phenotypes
      as observed in SIFa-ablated or depleted flies. Using a panel of neuron-specific
      Gal4 drivers, we further mapped SIFR effects to subsets of PI neurons. Taken
      together, these results reveal a novel physiological role of the neuropeptide
      SIFa/SIFR pathway to regulate sleep through sleep-promoting neural circuits in
      the PI of adult fly brains. 

PMID- 24658386
TI  - Probing differential optical and coverage behavior in nanotube-nanocrystal
      heterostructures synthesized by covalent versus non-covalent approaches.
AB  - Double-walled carbon nanotube (DWNT)-CdSe heterostructures with the individual
      nanoscale building blocks linked together by 4-aminothiophenol (4-ATP) have been
      successfully synthesized using two different and complementary routes, i.e.
      covalent attachment and non-covalent pi-pi stacking. Specifically, using a number
      of characterization methods, we have probed the effects of these differential
      synthetic coupling approaches on the resulting CdSe quantum dot (QD) coverage on
      the underlying nanotube template as well as the degree of charge transfer between
      the CdSe QDs and the DWNTs. In general, based on microscopy and spectroscopy data
      collectively, we noted that heterostructures generated by non-covalent pi-pi
      stacking interactions evinced not only higher QD coverage density but also
      possibly more efficient charge transfer behavior as compared with their
      counterparts produced using covalent linker-mediated protocols. 

PMID- 24658385
TI  - Transient receptor potential cation channel V1 (TRPV1) is degraded by starvation-
      and glucocorticoid-mediated autophagy.
AB  - A mammalian cell renovates itself by autophagy, a process through which cellular
      components are recycled to produce energy and maintain homeostasis. Recently, the
      abundance of gap junction proteins was shown to be regulated by autophagy during
      starvation conditions, suggesting that transmembrane proteins are also regulated
      by autophagy. Transient receptor potential vanilloid type 1 (TRPV1), an ion
      channel localized to the plasma membrane and endoplasmic reticulum (ER), is a
      sensory transducer that is activated by a wide variety of exogenous and
      endogenous physical and chemical stimuli. Intriguingly, the abundance of cellular
      TRPV1 can change dynamically under pathological conditions. However, the
      mechanisms by which the protein levels of TRPV1 are regulated have not yet been
      explored. Therefore, we investigated the mechanisms of TRPV1 recycling using HeLa
      cells constitutively expressing TRPV1. Endogenous TRPV1 was degraded in
      starvation conditions; this degradation was blocked by chloroquine (CLQ), 3MA, or
      downregulation of Atg7. Interestingly, a glucocorticoid (cortisol) was capable of
      inducing autophagy in HeLa cells. Cortisol increased cellular conversion of LC3-I
      to LC-3II, leading autophagy and resulting in TRPV1 degradation, which was
      similarly inhibited by treatment with CLQ, 3MA, or downregulation of Atg7.
      Furthermore, cortisol treatment induced the colocalization of GFP-LC3 with
      endogenous TRPV1. Cumulatively, these observations provide evidence that
      degradation of TRPV1 is mediated by autophagy, and that this pathway can be
      enhanced by cortisol. 

PMID- 24658387
TI  - Progressive occlusion of enterprise stent-assisted coiling of ruptured wide
      necked intracranial aneurysms and related factors on angiographic follow-up: a
      single-center experience with 468 patients.
AB  - This study was designed to assess the effect of the Enterprise stent on
      progressive occlusion of wide-necked aneurysms and to evaluate the association
      between dubious factors and progressive occlusion, which is a consecutive,
      retrospective, single-center study. Data from 468 patients with 495 wide-necked
      aneurysms, who had undergone Enterprise stent-assisted coiling (SAC) were
      reviewed, and the clinical outcomes and the angiographic results were analyzed. A
      14-month clinical follow-up was achieved in 421 of the 468 patients (90.0%),
      showing modified Rankin Scale (mRS) 0-1 in 364 (86.4%), mRS 2 in 17 (4.1%), mRS 3
      in 17 (4.1%), mRS 4-5 in 9 (2.1%), and mRS 6 in 14 (3.3%) patients. Overall, the
      morbidity and mortality were 10.2% and 3.3%, respectively. Initial angiographic
      results showed Raymond scale (RS)1 in 273 (55.2%), RS2 in 194 (39.2%), and RS3 in
      28 (5.6%) patients. Eight-month angiographic follow-up was available in 394 of
      495 patients (79.6%), and RS1 was seen in 315 (79.9%), RS2 in 65 (16.5%) and RS3
      in 14 (3.6%) cases. At the end of the follow-up, 115 of the 165 (69.7%) patients
      with initial RS2 and RS3 showed progressive occlusion. Statistical analysis
      showed no significant difference between progressive occlusion and age (p =
      0.654), sex (p = 0.016), aneurysm diameter (p = 0.010), neck size (p = 0.124),
      dome-to neck ratio (DNR) (p = 0.018) and location (p = 0.001) at the time of
      follow-up. SAC using Enterprise stent is not only feasible for wide-necked
      aneurysms, but can achieve a high rate of progressive occlusion with good
      clinical outcomes at medium-term follow-up. Patient age and aneurysm neck size
      showed no associated with progressive occlusion at follow-up, while sex, aneurysm
      diameter, DNR and location were significantly associated with progressive
      occlusion. 

PMID- 24658388
TI  - A fast, robust algorithm for power line interference cancellation in neural
      recording.
AB  - OBJECTIVE: Power line interference may severely corrupt neural recordings at
      50/60 Hz and harmonic frequencies. The interference is usually non-stationary and
      can vary in frequency, amplitude and phase. To retrieve the gamma-band
      oscillations at the contaminated frequencies, it is desired to remove the
      interference without compromising the actual neural signals at the interference
      frequency bands. In this paper, we present a robust and computationally efficient
      algorithm for removing power line interference from neural recordings. APPROACH:
      The algorithm includes four steps. First, an adaptive notch filter is used to
      estimate the fundamental frequency of the interference. Subsequently, based on
      the estimated frequency, harmonics are generated by using discrete-time
      oscillators, and then the amplitude and phase of each harmonic are estimated by
      using a modified recursive least squares algorithm. Finally, the estimated
      interference is subtracted from the recorded data. MAIN RESULTS: The algorithm
      does not require any reference signal, and can track the frequency, phase and
      amplitude of each harmonic. When benchmarked with other popular approaches, our
      algorithm performs better in terms of noise immunity, convergence speed and
      output signal-to-noise ratio (SNR). While minimally affecting the signal bands of
      interest, the algorithm consistently yields fast convergence (<100 ms) and
      substantial interference rejection (output SNR >30 dB) in different conditions of
      interference strengths (input SNR from -30 to 30 dB), power line frequencies (45
      65 Hz) and phase and amplitude drifts. In addition, the algorithm features a
      straightforward parameter adjustment since the parameters are independent of the
      input SNR, input signal power and the sampling rate. A hardware prototype was
      fabricated in a 65 nm CMOS process and tested. Software implementation of the
      algorithm has been made available for open access at
      https://github.com/mrezak/removePLI. SIGNIFICANCE: The proposed algorithm
      features a highly robust operation, fast adaptation to interference variations,
      significant SNR improvement, low computational complexity and memory requirement
      and straightforward parameter adjustment. These features render the algorithm
      suitable for wearable and implantable sensor applications, where reliable and
      real-time cancellation of the interference is desired.

PMID- 24658389
TI  - Healthy behavior change and cardiovascular outcomes in newly diagnosed type 2
      diabetic patients: a cohort analysis of the ADDITION-Cambridge study.
AB  - OBJECTIVE: To examine whether improvements in health behaviors are associated
      with reduced risk of cardiovascular disease (CVD) in individuals with newly
      diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: Population-based
      prospective cohort study of 867 newly diagnosed diabetic patients aged between 40
      and 69 years from the treatment phase of the ADDITION-Cambridge study. Because
      the results for all analyses were similar by trial arm, data were pooled, and
      results were presented for the whole cohort. Participants were identified via
      population-based stepwise screening between 2002 and 2006, and underwent
      assessment of physical activity (European Prospective Investigation into Cancer
      Norfolk Physical Activity Questionnaire), diet (plasma vitamin C and self
      report), and alcohol consumption (self-report) at baseline and 1 year. A
      composite primary CVD outcome was examined, comprised of cardiovascular
      mortality, nonfatal myocardial infarction, nonfatal stroke, and
      revascularization. RESULTS: After a median (interquartile range) follow-up period
      of 5.0 years (1.3 years), 6% of the cohort experienced a CVD event (12.2 per
      1,000 person-years; 95% CI 9.3-15.9). CVD risk was inversely related to the
      number of positive health behaviors changed in the year after diabetes diagnosis.
      The relative risk for primary CVD event in individuals who did not change any
      health behavior compared with those who adopted three/four healthy behaviors was
      4.17 (95% CI 1.02-17.09), adjusting for age, sex, study group, social class,
      occupation, and prescription of cardioprotective medication (P for trend =
      0.005). CONCLUSIONS: CVD risk was inversely associated with the number of healthy
      behavior changes adopted in the year after the diagnosis of diabetes.
      Interventions that promote early achievement of these goals in patients with
      newly diagnosed diabetes could help reduce the burden of diabetes-related
      morbidity and mortality.

PMID- 24658390
TI  - Living well with diabetes: 24-month outcomes from a randomized trial of telephone
      delivered weight loss and physical activity intervention to improve glycemic
      control.
AB  - OBJECTIVE: To evaluate the effectiveness of a telephone-delivered behavioral
      weight loss and physical activity intervention targeting Australian primary care
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Pragmatic randomized
      controlled trial of telephone counseling (n = 151) versus usual care (n = 151).
      Reported here are 18-month (end-of-intervention) and 24-month (maintenance)
      primary outcomes of weight, moderate-to-vigorous-intensity physical activity
      (MVPA; via accelerometer), and HbA1c level. Secondary outcomes include dietary
      energy intake and diet quality, waist circumference, lipid levels, and blood
      pressure. Data were analyzed via adjusted linear mixed models with multiple
      imputation of missing data. RESULTS: Relative to usual-care participants,
      telephone counseling participants achieved modest, but significant, improvements
      in weight loss (relative rate [RR] -1.42% of baseline body weight [95% CI -2.54
      to -0.30% of baseline body weight]), MVPA (RR 1.42 [95% CI 1.06-1.90]), diet
      quality (2.72 [95% CI 0.55-4.89]), and waist circumference (-1.84 cm [95% CI 
      3.16 to -0.51 cm]), but not in HbA1c level (RR 0.99 [95% CI 0.96-1.02]), or other
      cardio-metabolic markers. None of the outcomes showed a significant
      change/deterioration over the maintenance period. However, only the intervention
      effect for MVPA remained statistically significant at 24 months. CONCLUSIONS: The
      modest improvements in weight loss and behavior change, but the lack of changes
      in cardio-metabolic markers, may limit the utility, scalability, and
      sustainability of such an approach.

PMID- 24658391
TI  - Magnetic resonance neuroimaging study of brain structural differences in diabetic
      peripheral neuropathy.
AB  - OBJECTIVE: Diabetic peripheral neuropathy (DPN) has hitherto been considered a
      disease of the peripheral nervous system only, with central nervous system (CNS)
      involvement largely overlooked. The aim of this study was to investigate any
      differences in brain structure in subjects with DPN. RESEARCH DESIGN AND METHODS:
      Thirty-six subjects with type 1 diabetes (No DPN [n = 18], Painful DPN [n = 9],
      Painless DPN [n = 9]) underwent neurophysiological assessment to quantify the
      severity of DPN. All subjects, including 18 healthy volunteers (HVs), underwent
      volumetric brain magnetic resonance imaging at 3 Tesla. RESULTS: Adjusted
      peripheral gray matter volume was statistically significantly lower in subjects
      with painless and painful DPN (mean 599.6 mL [SEM 9.8 mL] and 585.4 mL [10.0 mL],
      respectively) compared with those with No DPN (626.5 mL [5.7 mL]) and HVs (639.9
      mL [7.2 mL]; ANCOVA, P = 0.001). The difference in adjusted peripheral gray
      matter volume between subjects with No DPN and HVs and those with Painful DPN and
      Painless DPN was not statistically significant (P = 0.16 and 0.30, respectively).
      Voxel-based morphometry analyses revealed greater localized volume loss in the
      primary somatosensory cortex, supramarginal gyrus, and cingulate cortex
      (corrected P < 0.05) in DPN subjects. CONCLUSIONS: This is the first study to
      focus on structural changes in the brain associated with DPN. Our findings
      suggest increased peripheral gray matter volume loss, localized to regions
      involved with somatosensory perception in subjects with DPN. This may have
      important implications for the long-term prognosis of DPN.

PMID- 24658392
TI  - Aberrant brain functional connectivity related to insulin resistance in type 2
      diabetes: a resting-state fMRI study.
AB  - OBJECTIVE: Type 2 diabetes is characterized by insulin resistance, which is
      involved in the development of Alzheimer disease. This study aims to investigate
      the relationship between abnormal resting-state brain functional connectivity and
      insulin resistance in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 30
      patients with type 2 diabetes and 31 healthy well-matched volunteers were
      prospectively examined. Resting-state brain functional connectivity analysis was
      used to examine the correlation between the posterior cingulate cortex (PCC) and
      whole-brain regions. The possible relationships between functional connectivity
      measures and insulin resistance were evaluated using the homeostasis model
      assessment of insulin resistance (HOMA-IR). RESULTS: Compared with healthy
      controls, we observed significantly decreased functional connectivity of the PCC
      within some selected regions, including the right middle temporal gyrus (MTG),
      left lingual gyrus, left middle occipital gyrus, and left precentral gyrus;
      increased functional connectivity of the PCC was detected in the left cerebellum
      posterior lobe, right superior frontal gyrus, and right middle frontal gyrus. A
      significant negative correlation was found between the PCC-right MTG connectivity
      and HOMA-IR in type 2 diabetic patients (P = 0.014; r = -0.446). CONCLUSIONS:
      Type 2 diabetic patients develop aberrant functional connectivity of the PCC,
      which is associated with insulin resistance in selected brain regions. Resting
      state connectivity disturbance of PCC-MTG may be a central role for evaluating
      the cognitive dysfunction in type 2 diabetes.

PMID- 24658393
TI  - Core-shell-like Y2O3:[(Tb3+-Yb3+), Li+]/CdZnS heterostructure synthesized by
      super-close-space sublimation for broadband down-conversion.
AB  - Combination with semiconductors is a promising approach to the realization of
      broadband excitation of light conversion materials based on rare earth compounds,
      to boost the energy efficiency of silicon solar cells. Cd(1-x)Zn(x)S is a wide
      bandgap semiconductor with large exciton binding energy. By changing its
      composition, the bandgap of Cd(1-x)Zn(x)S can be tuned to match the absorption of
      trivalent lanthanide (Ln) ions, which makes it a competent energy donor for the
      Ln(3+)-Yb(3+) couple. In this work, we designed a clean route to a broadband down
      converter based on a core-shell-like Y2O3:[(Tb(3+)-Yb(3+)), Li(+)]/Cd0.81Zn0.19S
      (CdZnS) heterostructure. By hot-pressing and subsequent annealing of a
      Y2O3:[(Tb(3+)-Yb(3+)), Li(+)]/CdZnS mixture, highly pure CdZnS was sublimated and
      deposited on the Y2O3:[(Tb(3+)-Yb(3+)), Li(+)] grains while maintaining the
      original composition of the precursor. The CdZnS shell acted as a light absorber
      and energy donor for the Tb(3+)-Yb(3+) quantum cutting couple. Because the use of
      solvents was avoided during the formation of the heterostructures, few impurities
      were incorporated into the samples, and the non-radiative transition was
      therefore markedly suppressed. The Y2O3:[(Tb(3+)-Yb(3+)), Li(+)]/CdZnS
      heterostructures possess strong near-infrared (NIR) luminescence from Yb(3+).
      Broadband down-conversion to the Yb(3+) NIR emission was obtained in a wide range
      of 250-650 nm.

PMID- 24658395
TI  - Non-vitamin K antagonist oral anticoagulants (NOACs): No longer new or novel.

PMID- 24658394
TI  - Next generation MUT-MAP, a high-sensitivity high-throughput microfluidics chip
      based mutation analysis panel.
AB  - Molecular profiling of tumor tissue to detect alterations, such as oncogenic
      mutations, plays a vital role in determining treatment options in oncology.
      Hence, there is an increasing need for a robust and high-throughput technology to
      detect oncogenic hotspot mutations. Although commercial assays are available to
      detect genetic alterations in single genes, only a limited amount of tissue is
      often available from patients, requiring multiplexing to allow for simultaneous
      detection of mutations in many genes using low DNA input. Even though next
      generation sequencing (NGS) platforms provide powerful tools for this purpose,
      they face challenges such as high cost, large DNA input requirement, complex data
      analysis, and long turnaround times, limiting their use in clinical settings. We
      report the development of the next generation mutation multi-analyte panel (MUT
      MAP), a high-throughput microfluidic, panel for detecting 120 somatic mutations
      across eleven genes of therapeutic interest (AKT1, BRAF, EGFR, FGFR3, FLT3, HRAS,
      KIT, KRAS, MET, NRAS, and PIK3CA) using allele-specific PCR (AS-PCR) and Taqman
      technology. This mutation panel requires as little as 2 ng of high quality DNA
      from fresh frozen or 100 ng of DNA from formalin-fixed paraffin-embedded (FFPE)
      tissues. Mutation calls, including an automated data analysis process, have been
      implemented to run 88 samples per day. Validation of this platform using plasmids
      showed robust signal and low cross-reactivity in all of the newly added assays
      and mutation calls in cell line samples were found to be consistent with the
      Catalogue of Somatic Mutations in Cancer (COSMIC) database allowing for direct
      comparison of our platform to Sanger sequencing. High correlation with NGS when
      compared to the SuraSeq500 panel run on the Ion Torrent platform in a FFPE
      dilution experiment showed assay sensitivity down to 0.45%. This multiplexed
      mutation panel is a valuable tool for high-throughput biomarker discovery in
      personalized medicine and cancer drug development. 

PMID- 24658396
TI  - Effect of repetitive transcranial magnetic stimulation over the cerebellum on
      patients with ataxia after posterior circulation stroke: A pilot study.
AB  - OBJECTIVE: To investigate the safety, feasibility and preliminary efficacy of low
      frequency repetitive transcranial magnetic stimulation (rTMS) over the cerebellum
      in ataxic patients with acute posterior circulation stroke. DESIGN: Randomized,
      double-blind, sham-controlled pilot study. PATIENTS: Thirty-two ataxic patients
      with posterior circulation stroke were randomized to real (n = 22) and sham (n =
      10) rTMS groups. METHODS: Patients received 5 15-min sessions of 1 Hz cerebellar
      rTMS over 5 consecutive days. Compliance and adverse events for the rTMS sessions
      were checked. The 10-m walk test (10MWT) and Berg Balance Scale (BBS) were
      completed before rTMS, immediately and 1 month after the last rTMS session.
      RESULTS: Compliance with the rTMS was 100% and no adverse events were reported in
      either group. 10MWT and BBS of real rTMS group improved significantly (p < 0.01).
      Percentage changes immediately after the last rTMS session for time and steps in
      the 10MWT and BBS in the real vs sham group were: -16.7 +/- 35.1% vs -8.4 +/-
      72.5%, -8.5 +/- 23.0% vs -0.3 +/- 28.4% and 46.4 +/- 100.2% vs 36.6 +/- 71.6%,
      respectively. CONCLUSION: This study demonstrated that 1 Hz rTMS over the
      cerebellum is safe, feasible and may have a beneficial effect in ataxic patients
      with posterior circulation stroke.

PMID- 24658397
TI  - Catalytic activity of Pd-doped Cu nanoparticles for hydrogenation as a single
      atom-alloy catalyst.
AB  - The single atom alloy of extended surfaces is known to provide remarkably
      enhanced catalytic performance toward heterogeneous hydrogenation. Here we
      demonstrate from first principles calculations that this approach can be extended
      to nanostructures, such as bimetallic nanoparticles. The catalytic properties of
      the single-Pd-doped Cu55 nanoparticles have been systemically examined for H2
      dissociation as well as H atom adsorption and diffusion, following the concept of
      single atom alloy. It is found that doping a single Pd atom at the edge site of
      the Cu55 shell can considerably reduce the activation energy of H2 dissociation,
      while the single Pd atom doped at the top site or in the inner layers is much
      less effective. The H atom adsorption on Cu55 is slightly stronger than that on
      the Cu(111) surface; however, a larger nanoparticle that contains 147 atoms could
      effectively recover the weak binding of the H atoms. We have also investigated
      the H atom diffusion on the 55-atom nanoparticle and found that spillover of the
      produced H atoms could be a feasible process due to the low diffusion barriers.
      Our results have demonstrated that facile H2 dissociation and weak H atom
      adsorption could be combined at the nanoscale. Moreover, the effects of doping
      one more Pd atom on the H2 dissociation and H atom adsorption have also been
      investigated. We have found that both the doping Pd atoms in the most stable
      configuration could independently exhibit their catalytic activity, behaving as
      two single-atom-alloy catalysts. 

PMID- 24658398
TI  - Kif4 interacts with EB1 and stabilizes microtubules downstream of Rho-mDia in
      migrating fibroblasts.
AB  - Selectively stabilized microtubules (MTs) form in the lamella of fibroblasts and
      contribute to cell migration. A Rho-mDia-EB1 pathway regulates the formation of
      stable MTs, yet how selective stabilization of MTs is achieved is unknown.
      Kinesin activity has been implicated in selective MT stabilization and a number
      of kinesins regulate MT dynamics both in vitro and in cells. Here, we show that
      the mammalian homolog of Xenopus XKLP1, Kif4, is both necessary and sufficient
      for the induction of selective MT stabilization in fibroblasts. Kif4 localized to
      the ends of stable MTs and participated in the Rho-mDia-EB1 MT stabilization
      pathway since Kif4 depletion blocked mDia- and EB1-induced selective MT
      stabilization and EB1 was necessary for Kif4 induction of stable MTs. Kif4 and
      EB1 interacted in cell extracts, and binding studies revealed that the tail
      domain of Kif4 interacted directly with the N-terminal domain of EB1. Consistent
      with its role in regulating formation of stable MTs in interphase cells, Kif4
      knockdown inhibited migration of cells into wounded monolayers. These data
      identify Kif4 as a novel factor in the Rho-mDia-EB1 MT stabilization pathway and
      cell migration. 

PMID- 24658399
TI  - Tumor necrosis factor-alpha impairs oligodendroglial differentiation through a
      mitochondria-dependent process.
AB  - Mitochondrial defects, affecting parameters such as mitochondrial number and
      shape, levels of respiratory chain complex components and markers of oxidative
      stress, have been associated with the appearance and progression of multiple
      sclerosis. Nevertheless, mitochondrial physiology has never been monitored during
      oligodendrocyte progenitor cell (OPC) differentiation, especially in OPCs
      challenged with proinflammatory cytokines. Here, we show that tumor necrosis
      factor alpha (TNF-alpha) inhibits OPC differentiation, accompanied by altered
      mitochondrial calcium uptake, mitochondrial membrane potential, and respiratory
      complex I activity as well as increased reactive oxygen species production.
      Treatment with a mitochondrial uncoupler (FCCP) to mimic mitochondrial impairment
      also causes cells to accumulate at the progenitor stage. Interestingly, AMP
      activated protein kinase (AMPK) levels increase during TNF-alpha exposure and
      inhibit OPC differentiation. Overall, our data indicate that TNF-alpha induces
      metabolic changes, driven by mitochondrial impairment and AMPK activation,
      leading to the inhibition of OPC differentiation. 

PMID- 24658400
TI  - Genetic deletion of the mitochondrial phosphate carrier desensitizes the
      mitochondrial permeability transition pore and causes cardiomyopathy.
AB  - The mitochondrial phosphate carrier (PiC) is critical for ATP synthesis by
      serving as the primary means for mitochondrial phosphate import across the inner
      membrane. In addition to its role in energy production, PiC is hypothesized to
      have a role in cell death as either a component or a regulator of the
      mitochondrial permeability transition pore (MPTP) complex. Here, we have
      generated a mouse model with inducible and cardiac-specific deletion of the
      Slc25a3 gene (PiC protein). Loss of PiC protein did not prevent MPTP opening,
      suggesting it is not a direct pore-forming component of this complex. However,
      Slc25a3 deletion in the heart blunted MPTP opening in response to Ca(2+)
      challenge and led to a greater Ca(2+) uptake capacity. This desensitization of
      MPTP opening due to loss or reduction in PiC protein attenuated cardiac ischemic
      reperfusion injury, as well as partially protected cells in culture from Ca(2+)
      overload induced death. Intriguingly, deletion of the Slc25a3 gene from the heart
      long-term resulted in profound hypertrophy with ventricular dilation and
      depressed cardiac function, all features that reflect the cardiomyopathy observed
      in humans with mutations in SLC25A3. Together, these results demonstrate that
      although the PiC is not a direct component of the MPTP, it can regulate its
      activity, suggesting a novel therapeutic target for reducing necrotic cell death.
      In addition, mice lacking Slc25a3 in the heart serve as a novel model of
      metabolic, mitochondrial-driven cardiomyopathy. 

PMID- 24658401
TI  - The novel miR-9500 regulates the proliferation and migration of human lung cancer
      cells by targeting Akt1.
AB  - MicroRNAs have crucial roles in lung cancer cell development. They regulate cell
      growth, proliferation and migration by mediating the expression of tumor
      suppressor genes and oncogenes. We identified and characterized the novel miR
      9500 in human lung cancer cells. The miR-9500 forms a stem-loop structure and is
      conserved in other mammals. The expression levels of miR-9500 were reduced in
      lung cancer cells and lung cancer tissues compared with normal tissues, as
      verified by TaqMan miRNA assays. It was confirmed that the putative target gene,
      Akt1, was directly suppressed by miR-9500, as demonstrated by a luciferase
      reporter assay. The miR-9500 significantly repressed the protein expression
      levels of Akt1, as demonstrated via western blot, but did not affect the
      corresponding mRNA levels. Akt1 has an important role in lung carcinogenesis, and
      depletion of Akt1 has been shown to have antiproliferative and anti-migratory
      effects in previous studies. In the current study, the overexpression of miR-9500
      inhibited cell proliferation and the expression of cell cycle-related proteins.
      Likewise, the overexpression of miR-9500 impeded cell migration in human lung
      cancer cells. In an in vivo assay, miR-9500 significantly suppressed Fluc
      expression compared with NC and ASO-miR-9500, suggesting that cell proliferation
      was inhibited in nude mice. Likewise, miR-9500 repressed tumorigenesis and
      metastasis by targeting Akt1. These data indicate that miR-9500 might be
      applicable for lung cancer therapy. 

PMID- 24658402
TI  - Divergent chemosymbiosis-related characters in Thyasira cf. gouldi (Bivalvia:
      Thyasiridae).
AB  - Within the marine bivalve family Thyasiridae, some species have bacterial
      chemosymbionts associated with gill epithelial cells while other species are
      asymbiotic. Although the abundance of symbionts in a particular thyasirid species
      may vary, the structure of their gills (i.e., their frontal-abfrontal thickening)
      does not. We examined gill structure in a species tentatively identified as
      Thyasira gouldi from a Northwest Atlantic fjord (Bonne Bay, Newfoundland) and
      found remarkable differences among specimens. Some individuals had thickened gill
      filaments with abundant symbionts, while others had thin filaments and lacked
      symbionts. We could differentiate symbiotic and asymbiotic specimens based on the
      size and outline of their shell as well as 18S rRNA, 28S rRNA and CO1 sequences.
      The wide morphological, genetic and symbiosis-related disparity described herein
      suggests that chemosymbiosis may influence host divergence, and that Thyasira
      gouldi forms a cryptic species complex. 

PMID- 24658403
TI  - HIV-1 Nef induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt
      pathway and utilizes NF-kB, CEBP and AP-1 transcription factors.
AB  - The prevalence of HIV-associated neurocognitive disorders (HAND) remains high in
      patients infected with HIV-1. The production of pro-inflammatory cytokines by
      astrocytes/microglia exposed to viral proteins is thought to be one of the
      mechanisms leading to HIV-1- mediated neurotoxicity. In the present study we
      examined the effects of Nef on CCL5 induction in astrocytes. The results
      demonstrate that CCL5 is significantly induced in Nef-transfected SVGA
      astrocytes. To determine the mechanisms responsible for the increased CCL5 caused
      by Nef, we employed siRNA and chemical antagonists. Antagonists of NF-kappaB,
      PI3K, and p38 significantly reduced the expression levels of CCL5 induced by Nef
      transfection. Furthermore, specific siRNAs demonstrated that the Akt, p38MAPK, NF
      kappaB, CEBP, and AP-1 pathways play a role in Nef-mediated CCL5 expression. The
      results demonstrated that the PI3K/Akt and p38 MAPK pathways, along with the
      transcription factors NF-kappaB, CEBP, and AP-1, are involved in Nef-induced CCL5
      production in astrocytes. 

PMID- 24658404
TI  - Allopregnanolone modulation of HPA axis function in the adult rat.
AB  - RATIONALE: GABAergic neuronal circuits regulate neuroendocrine stress response,
      and the most potent positive endogenous modulator of GABAA receptor function is
      allopregnanolone. This neurosteroid acts in a nongenomic manner to selectively
      increase the inhibitory signal meditated by GABAA receptors; in addition, it also
      induces long-lasting changes in the expression of specific GABAA receptor
      subunits in various brain regions, with consequent changes in receptor function.
      OBJECTIVE: The objective of this review is to summarize our findings on emotional
      state and stress responsiveness in three animal models in which basal brain
      concentrations of allopregnanolone differ. It is postulated that individual
      differences in allopregnanolone levels can influence general resilience. RESULTS:
      The results showed that there is an apparent correlation between endogenous
      levels of brain allopregnanolone and basal and stress-stimulated HPA axis
      activity. CONCLUSION: The relationship between endogenous brain levels of
      allopregnanolone and HPA axis activity and function sustains the therapeutic
      potential of this neurosteroid for the treatment of stress-associated disorders.

PMID- 24658405
TI  - Induction of nuclear translocation of mutant cytoplasmic p53 by geranylgeranoic
      acid in a human hepatoma cell line.
AB  - Mutant p53 proteins in human hepatoma cell lines such as HuH-7 (Y220C) and
      PLC/PRF/5 (R249S) accumulate in the cytoplasm, and lose their transcriptional
      function. Geranylgeranoic acid (GGA) is a naturally occurring acyclic diterpenoid
      that induces cell death in both cell lines, but not in HepG2 cells harboring wild
      type p53. Here, we demonstrate that micromolar concentrations of GGA induce a
      rapid nuclear translocation of cytoplasmic p53 in both p53-mutant cell lines and
      p53 knockdown attenuates GGA-induced cell death in HuH-7 cells. Cell-free
      experiments demonstrate that GGA is able to release 670-kD p53-containing
      complexes from putative huge macromolecular aggregates in post-mitochondrial
      fractions as revealed on blue-native gradient PAGE. Among several p53-target
      genes tested, GGA upregulates PUMA gene expression, and ivermectin, an inhibitor
      for importin alpha/beta, blocks GGA-induced nuclear translocation of cytoplasmic
      p53 and suppresses GGA-induced upregulation of PUMA mRNA levels in HuH-7 cells.
      Taken together, these data suggest that GGA treatment stimulates a nuclear
      translocation of mutant p53 through its dissociation from cytoplasmic aggregates,
      which may be essential for GGA-induced cell death. 

PMID- 24658406
TI  - A general method for assessing brain-computer interface performance and its
      limitations.
AB  - OBJECTIVE: When researchers evaluate brain-computer interface (BCI) systems, we
      want quantitative answers to questions such as: How good is the system's
      performance? How good does it need to be? and: Is it capable of reaching the
      desired level in future? In response to the current lack of objective,
      quantitative, study-independent approaches, we introduce methods that help to
      address such questions. We identified three challenges: (I) the need for
      efficient measurement techniques that adapt rapidly and reliably to capture a
      wide range of performance levels; (II) the need to express results in a way that
      allows comparison between similar but non-identical tasks; (III) the need to
      measure the extent to which certain components of a BCI system (e.g. the signal
      processing pipeline) not only support BCI performance, but also potentially
      restrict the maximum level it can reach. APPROACH: For challenge (I), we
      developed an automatic staircase method that adjusted task difficulty adaptively
      along a single abstract axis. For challenge (II), we used the rate of information
      gain between two Bernoulli distributions: one reflecting the observed success
      rate, the other reflecting chance performance estimated by a matched random-walk
      method. This measure includes Wolpaw's information transfer rate as a special
      case, but addresses the latter's limitations including its restriction to item
      selection tasks. To validate our approach and address challenge (III), we
      compared four healthy subjects' performance using an EEG-based BCI, a 'Direct
      Controller' (a high-performance hardware input device), and a 'Pseudo-BCI
      Controller' (the same input device, but with control signals processed by the BCI
      signal processing pipeline). MAIN RESULTS: Our results confirm the repeatability
      and validity of our measures, and indicate that our BCI signal processing
      pipeline reduced attainable performance by about 33% (21 bits min(-1)).
      SIGNIFICANCE: Our approach provides a flexible basis for evaluating BCI
      performance and its limitations, across a wide range of tasks and task
      difficulties.

PMID- 24658409
TI  - Nurses' competencies in disaster nursing: implications for curriculum development
      and public health.
AB  - The purpose of this study was to explore Hong Kong nurses' perceptions of
      competencies required for disaster nursing. Focus group interviews and written
      inquiry were adopted to solicit nurses' perceived required competencies for
      disaster care. A total of 15 nurses were interviewed and 30 nurses completed the
      written inquiry on their perceived competencies related to disaster nursing. The
      International Council for Nurses' (ICN) framework of disaster nursing
      competencies, consisting of four themes and ten domains, was used to tabulate the
      perceived competencies for disaster nursing reported by nurses. The most
      mentioned required competencies were related to disaster response; with the
      ethical and legal competencies for disaster nursing were mostly neglected by
      nurses in Hong Kong. With the complexity nature of disasters, special
      competencies are required if nurses are to deal with adverse happenings in their
      serving community. Nurses' perceived disaster nursing competencies reported by
      nurses were grossly inadequate, demonstrating the needs to develop a
      comprehensive curriculum for public health. The establishment of a set of tailor
      made disaster nursing core competencies for the community they served is the
      first step in preparing nurses to deal with disastrous situations for the health
      of the public. 

PMID- 24658408
TI  - Feasibility of silver doped TiO2/glass fiber photocatalyst under visible
      irradiation as an indoor air germicide.
AB  - This study investigated the feasibility of using Ag-TiO2 photocatalyst supported
      on glass fiber (Ag-TiO2/GF) prepared by a sol-gel method as an indoor air
      germicide. An experimental model was designed to investigate the bacterial
      disinfection efficiency of Staphylococcus (Staph), the most popular bacterium in
      hospitals in Korea, by the Ag-TiO2/GF photocatalyst. The silver content in
      Ag/TiO2 was altered from 1 to 10% to investigate the optimal ratio of Ag doped on
      TiO2/glass fiber (TiO2/GF) for photocatalytic disinfection of Staph. This study
      confirmed that Ag in Ag-TiO2/GF could work as an electron sink or donor to
      increase photocatalytic activity and promote the charge separation of electron
      hole pairs generated from TiO2 after photon absorption. Ag also acts as an
      intermediate agent for the transfer of photo-generated electrons from the valence
      band of TiO2 to an acceptor (O2 gas) to promote photo-oxidation processes. The
      photocatalytic disinfection activity of Ag-TiO2/GF under visible light increased
      with the increase in silver content up to 7.5% and then slightly decreased with
      further increasing silver content. The highest disinfection efficiency and
      disinfection capacity of Staph using 7.5% Ag-TiO2/GF were 75.23% and 20 (CFU?s
      1?cm-2) respectively. The medium level of humidity of 60% +/- 5% showed better
      photocatalytic disinfection than the lower (40% +/- 5%) or higher (80% +/- 5%)
      levels. 

PMID- 24658407
TI  - AltitudeOmics: the integrative physiology of human acclimatization to hypobaric
      hypoxia and its retention upon reascent.
AB  - An understanding of human responses to hypoxia is important for the health of
      millions of people worldwide who visit, live, or work in the hypoxic environment
      encountered at high altitudes. In spite of dozens of studies over the last 100
      years, the basic mechanisms controlling acclimatization to hypoxia remain largely
      unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to
      describe a phenotype for successful acclimatization and assess its retention and
      2) use these findings as a foundation for companion mechanistic studies. Our
      approach was to characterize acclimatization by measuring changes in arterial
      oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS),
      cognitive function, and exercise performance in 21 subjects as they acclimatized
      to 5260 m over 16 days. We then focused on the retention of acclimatization by
      having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at
      1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation
      and [Hb] (compared to acute hypoxia: PaO2 rose 9+/-4 mmHg to 45+/-4 while PaCO2
      dropped a further 6+/-3 mmHg to 21+/-3, and [Hb] rose 1.8+/-0.7 g/dL to 16+/-2
      g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise
      performance by 8+/-8% (all changes p<0.01). Upon reascent, we observed retention
      of arterial oxygenation but not [Hb], protection from AMS, retention of exercise
      performance, less retention of cognitive function; and noted that some of these
      effects lasted for 21 days. Taken together, these findings reveal new information
      about retention of acclimatization, and can be used as a physiological foundation
      to explore the molecular mechanisms of acclimatization and its retention. 

PMID- 24658410
TI  - Heat-related deaths in hot cities: estimates of human tolerance to high
      temperature thresholds.
AB  - In this study we characterized the relationship between temperature and mortality
      in central Arizona desert cities that have an extremely hot climate.
      Relationships between daily maximum apparent temperature (ATmax) and mortality
      for eight condition-specific causes and all-cause deaths were modeled for all
      residents and separately for males and females ages <65 and >= 65 during the
      months May-October for years 2000-2008. The most robust relationship was between
      ATmax on day of death and mortality from direct exposure to high environmental
      heat. For this condition-specific cause of death, the heat thresholds in all
      gender and age groups (ATmax = 90-97  degrees F; 32.2-36.1  degrees C) were below
      local median seasonal temperatures in the study period (ATmax = 99.5  degrees F;
      37.5  degrees C). Heat threshold was defined as ATmax at which the mortality
      ratio begins an exponential upward trend. Thresholds were identified in younger
      and older females for cardiac disease/stroke mortality (ATmax = 106 and 108 
      degrees F; 41.1 and 42.2  degrees C) with a one-day lag. Thresholds were also
      identified for mortality from respiratory diseases in older people (ATmax = 109 
      degrees F; 42.8  degrees C) and for all-cause mortality in females (ATmax = 107 
      degrees F; 41.7  degrees C) and males <65 years (ATmax = 102  degrees F; 38.9 
      degrees C). Heat-related mortality in a region that has already made some
      adaptations to predictable periods of extremely high temperatures suggests that
      more extensive and targeted heat-adaptation plans for climate change are needed
      in cities worldwide.

PMID- 24658411
TI  - Temporal trends and correlates of physical activity, sedentary behaviour, and
      physical fitness among school-aged children in Sub-Saharan Africa: a systematic
      review.
AB  - Recent physical activity (PA) and fitness transitions, identified as behavioural
      shifts from traditionally active lifestyles to more industralised and sedentary
      lifestyles, have been observed among school-aged children. There is a wealth of
      supporting evidence of such behavioural transitions in high income countries;
      however, a paucity of data on lower income countries exists. These transitions
      pose a particular threat to the welfare of children by accelerating the onset of
      chronic diseases. This systematic review investigated the evidence for a PA and
      fitness transition among Sub-Saharan Africa's school-aged children. Temporal
      trends and correlates of PA, SB, and fitness were examined. Studies were
      identified by searching the Medline, Embase, Africa Index Medicus, Global Health,
      Geobase, and EPPI-Centre electronic databases, and were included if they measured
      outcomes of interest in apparently healthy samples of children (5-17 years). A
      total of 71 articles met the inclusion criteria (40 informed PA, 17 informed SB,
      and 37 informed fitness). Vast heterogeneity in study methodology complicated
      analysis of transitions over time and no temporal trends were immediately
      discernible. However, higher socioeconomic status, urban living, and female
      children were found to engage in lower levels of PA, higher SB, and performed
      worse on aerobic fitness measures compared to lower socioeconomic status, rural
      living, and male children. Data revealed that urbanization was associated with a
      trend towards decreased PA, increased SB, and decreased aerobic fitness over
      time. Representative, temporally sequenced data examining a PA and fitness
      transition are lacking in this region (PROSPERO Registration Number:
      CRD42013004399). 

PMID- 24658412
TI  - Implementing cargo movement into climate based risk assessment of vector-borne
      diseases.
AB  - During the last decades the disease vector Aedes albopictus (Asian tiger
      mosquito) has rapidly spread around the globe. Global shipment of goods
      contributes to its permanent introduction. Invaded regions are facing novel and
      serious public health concerns, especially regarding the transmission of formerly
      non-endemic arboviruses such as dengue and chikungunya. The further development
      and potential spread to other regions depends largely on their climatic
      suitability. Here, we have developed a tool for identifying and prioritizing
      European areas at risk for the establishment of Aedes albopictus by taking into
      account, for the first time, the freight imports from this mosquito's endemic
      countries and the climate suitability at harbors and their surrounding regions.
      In a second step we consider the further transport of containers by train and
      inland waterways because these types of transport can be well controlled. We
      identify European regions at risk, where a huge amount of transported goods meet
      climatically suitable conditions for the disease vector. The current and future
      suitability of the climate for Aedes albopictus was modeled by a correlative
      niche model approach and the Regional Climate Model COSMO-CLM. This risk
      assessment combines impacts of globalization and global warming to improve
      effective and proactive interventions in disease vector surveillance and control
      actions. 

PMID- 24658413
TI  - Remarkable recovery and colonization behaviour of methane oxidizing bacteria in
      soil after disturbance is controlled by methane source only.
AB  - Little is understood about the relationship between microbial assemblage history,
      the composition and function of specific functional guilds and the ecosystem
      functions they provide. To learn more about this relationship we used methane
      oxidizing bacteria (MOB) as model organisms and performed soil microcosm
      experiments comprised of identical soil substrates, hosting distinct overall
      microbial diversities(i.e., full, reduced and zero total microbial and MOB
      diversities). After inoculation with undisturbed soil, the recovery of MOB
      activity, MOB diversity and total bacterial diversity were followed over 3 months
      by methane oxidation potential measurements and analyses targeting pmoA and 16S
      rRNA genes. Measurement of methane oxidation potential demonstrated different
      recovery rates across the different treatments. Despite different starting
      microbial diversities, the recovery and succession of the MOB communities
      followed a similar pattern across the different treatment microcosms. In this
      study we found that edaphic parameters were the dominant factor shaping microbial
      communities over time and that the starting microbial community played only a
      minor role in shaping MOB microbial community.

PMID- 24658415
TI  - NADPH thioredoxin reductase C is involved in redox regulation of the Mg-chelatase
      I subunit in Arabidopsis thaliana chloroplasts.

PMID- 24658414
TI  - Spatial scaling effects on soil bacterial communities in Malaysian tropical
      forests.
AB  - Spatial scaling to some extent determines biodiversity patterns in larger
      organisms, but its role in microbial diversity patterns is much less understood.
      Some studies have shown that bacterial community similarity decreases with
      distance, whereas others do not support this. Here, we studied soil bacterial
      communities of tropical rainforest in Malaysia at two spatial scales: a local
      scale with samples spaced every 5 mover a 150-m transect, and a regional scale
      with samples 1 to 1,800 km apart. PCR-amplified soil DNA for the bacterial 16S
      rRNA gene targeting the V1-V3 region was pyrosequenced using Roche/454 GS FLX
      Titanium platform. A ranked partial Mantel test showed a weak correlation between
      spatial distance and whole bacterial community dissimilarity, but only at the
      local scale. In contrast, environmental distance was highly correlated with
      community dissimilarity at both spatial scales,stressing the greater role of
      environmental variables rather than spatial distance in determining bacterial
      community variation at different spatial scales. Soil pH was the only
      environmental parameter that significantly explained the variance in bacterial
      community at the local scale, whereas total nitrogen and elevation were
      additional important factors at the regional scale.We obtained similar results at
      both scales when only the most abundant OTUs were analyzed. A variance
      partitioning analysis showed that environmental variables contributed more to
      bacterial community variation than spatial distance at both scales. In total, our
      results support a strong influence of the environment in determining bacterial
      community composition in the rainforests of Malaysia. However, it is possible
      that the remaining spatial distance effect is due to some of the myriad of other
      environmental factors which were not considered here, rather than dispersal
      limitation.

PMID- 24658416
TI  - Transcriptional repression by histone deacetylases in plants.
AB  - Reversible histone acetylation and deacetylation at the N-terminus of histone
      tails play crucial roles in regulation of eukaryotic gene activity. Acetylation
      of core histones usually induces an 'open' chromatin structure and is associated
      with gene activation, whereas deacetylation of histone is often correlated with
      'closed' chromatin and gene repression. Histone deacetylation is catalyzed by
      histone deacetylases (HDACs). A growing number of studies have demonstrated the
      importance of histone deacetylation/acetylation on genome stability,
      transcriptional regulation, and development in plants. Furthermore, HDACs were
      shown to interact with various chromatin remolding factors and transcription
      factors involved in transcriptional repression in multiple developmental
      processes. In this review, we summarized recent findings on the transcriptional
      repression mediated by HDACs in plants. 

PMID- 24658417
TI  - Induced deactivation of genes encoding chlorophyll biosynthesis enzymes
      disentangles tetrapyrrole-mediated retrograde signaling.
AB  - In photosynthetic organisms, tetrapyrrole-mediated retrograde signals are
      proposed to contribute to a balanced nuclear gene expression (NGE) in response to
      metabolic activity in chloroplasts. We followed an experimental short-term
      approach that allowed the assessment of modified NGE during the first hours of
      specifically modified enzymatic steps of the Mg branch of tetrapyrrole
      biosynthesis, when pleiotropic effects of other signals can be avoided. In
      response to 24-h-induced silencing of CHLH, CHLM, and CHL27 encoding the CHLH
      subunit of Mg chelatase, the Mg protoporphyrin methyltransferase and Mg
      protoporphyrin monomethylester cyclase, respectively, deactivated gene expression
      rapidly led to reduced activity of the corresponding enzymes and altered Mg
      porphyrin levels. But NGE was not substantially altered. When these three genes
      were continuously inactivated for up to 4 d, changes of transcript levels of
      nuclear genes were determined. CHL27 silencing for more than 24h results in
      necrotic leaf lesions and modulated transcript levels of oxidative stress
      responsive and photosynthesis-associated nuclear genes (PhANGs). The prolonged
      deactivation of CHLH and CHLM results in slightly elevated transcript levels of
      PhANGs and tetrapyrrole-associated genes. These time-resolved studies indicate a
      complex scenario for the contribution of tetrapyrrole biosynthesis on NGE
      mediated by (1)O2-induced signaling and feedback-regulated ALA synthesis. 

PMID- 24658418
TI  - Synthesis, antiradical activity and in vitro cytotoxicity of novel organotin
      complexes based on 2,6-di-tert-butyl-4-mercaptophenol.
AB  - A series of organotin complexes with Sn-S bonds of formulae Me2Sn(SR)2 (1);
      Et2Sn(SR)2 (2); (n-Bu)2Sn(SR)2 (3); Ph2Sn(SR)2 (4); R2Sn(SR)2 (5); Me3SnSR (6);
      Ph3SnSR (7) (R = 3,5-di-tert-butyl-4-hydroxyphenyl) were synthesized and
      characterized by elemental analysis, (1)H, (13)C NMR, and IR. The crystal
      structures of compounds 1, 4, 5, and 7 were determined by X-ray diffraction
      analysis. The tetrahedral geometry around the Sn center in the monocrystals of 1,
      4, 5, and 7 was confirmed by X-ray crystallography. The high radical scavenging
      activity of the complexes was confirmed spectrophotometrically in a DPPH-test.
      The binding affinity of 1-7 and the starting R2SnCl2 (8) towards tubulin through
      their interaction with SH groups of proteins was studied. It was found that the
      hindered organotin complexes could interact with the colchicine site of tubulin,
      which makes them promising antimitotic drugs. Compounds 1-8 were tested for their
      in vitro cytotoxicity against human breast (MCF-7) and human cervix (HeLa)
      adenocarcinoma cells. Complexes 1-8 were also tested against normal human fetal
      lung fibroblast cells (MRC-5). Complexes 2-4 and 8 exhibit significantly lower
      cytostatic activity against the normal MRC-5 cell line compared to the tumor cell
      lines MCF-7 and HeLa used. A high activity against both cell lines 250 nM (MCF-7)
      and 160 nM (HeLa) was determined for the triphenyltin complex 7 while the
      introduction of hindered phenol groups decreases the cytotoxicity of the
      complexes against normal cells.

PMID- 24658419
TI  - Dissecting the p53-Mdm2 feedback loop in vivo: uncoupling the role in p53
      stability and activity.
AB  - The p53-Mdm2 feedback loop is thought to be the main mechanism by which p53
      autoregulates its levels and activity after DNA damage. We tested this paradigm
      in a genetically engineered mouse model in which the feedback loop was disrupted
      by point mutations in the p53 binding site of the Mdm2 promoter. We noted that
      while the p53-Mdm2 feedback loop is required to regulate p53 activity especially
      in the hematopoietic system in response to DNA damage, its role in development
      and in regulating the stability of p53 is dispensable. In the present study we
      have extended our characterization of this mouse model and show that the kinetics
      of p53 degradation is also unchanged in mouse embryonic fibroblasts (MEFs).
      Additionally, MG132 experiments indicate that other E3-ligases regulate p53
      stability. Also, Mdm4 cooperates in inhibition of p53 activity and levels in
      these mice. Finally, we show in this system that enhanced acute p53 response does
      not promote aging or protect against late term tumorigenesis. We also discuss
      future perspectives for this study. 

PMID- 24658421
TI  - Internal photoemission from plasmonic nanoparticles: comparison between surface
      and volume photoelectric effects.
AB  - We study the emission of photoelectrons from plasmonic nanoparticles into a
      surrounding matrix. We consider two mechanisms of electron emission from the
      nanoparticles--surface and volume ones--and use models for these two mechanisms
      which allow us to obtain analytical results for the photoelectron emission rate
      from a nanoparticle. Calculations have been carried out for a step potential at
      the surface of a spherical nanoparticle, and a simple model for the hot electron
      cooling has been used. We highlight the effect of the discontinuity of the
      dielectric permittivity at the nanoparticle boundary in the surface mechanism,
      which leads to a substantial (by ~5 times) increase of the internal photoelectron
      emission rate from a nanoparticle compared to the case when such a discontinuity
      is absent. For a plasmonic nanoparticle, a comparison of the two photoeffect
      mechanisms was undertaken for the first time which showed that the surface
      photoeffect can in the general case be larger than the volume one, which agrees
      with the results obtained for a flat metal surface first formulated by Tamm and
      Schubin in their pioneering development of a quantum-mechanical theory of
      photoeffect in 1931. In accordance with our calculations, this possible
      predominance of the surface effect is based on two factors: (i) effective cooling
      of hot carriers during their propagation from the volume of the nanoparticle to
      its surface in the scenario of the volume mechanism and (ii) strengthening of the
      surface mechanism through the effect of the discontinuity of the dielectric
      permittivity at the nanoparticle boundary. The latter is stronger at relatively
      lower photon energies and correspondingly is more substantial for internal
      photoemission than for an external one. We show that in the general case, it is
      essential to take both mechanisms into account in the development of devices
      based on the photoelectric effect and when considering hot electron emission from
      a plasmonic nanoantenna.

PMID- 24658420
TI  - Lactosylceramide promotes hypertrophy through ROS generation and activation of
      ERK1/2 in cardiomyocytes.
AB  - Hypertrophy is central to several heart diseases; however, not much is known
      about the role of glycosphingolipids (GSLs) in this phenotype. Since GSLs have
      been accorded several physiological functions, we sought to determine whether
      these compounds affect cardiac hypertrophy. By using a rat cardiomyoblast cell
      line, H9c2 cells and cultured primary neonatal rat cardiomyocytes, we have
      determined the effects of GSLs on hypertrophy. Our study comprises (a)
      measurement of [(3)H]-leucine incorporation into protein, (b) measurement of cell
      size and morphology by immunofluorescence microscopy and (c) real-time
      quantitative mRNA expression assay for atrial natriuretic peptide and brain
      natriuretic peptide. Phenylephrine (PE), a well-established agonist of cardiac
      hypertrophy, served as a positive control in these studies. Subsequently,
      mechanistic studies were performed to explore the involvement of various
      signaling transduction pathways that may contribute to hypertrophy in these
      cardiomyocytes. We observed that lactosylceramide specifically exerted a
      concentration- (50-100 uM) and time (48 h)-dependent increase in hypertrophy in
      cardiomyocytes but not a library of other structurally related GSLs. Further, in
      cardiomyocytes, LacCer generated reactive oxygen species, stimulated the
      phosphorylation of p44 mitogen activated protein kinase and protein kinase-C, and
      enhanced c-jun and c-fos expression, ultimately leading to hypertrophy. In
      summary, we report here that LacCer specifically induces hypertrophy in
      cardiomyocytes via an "oxygen-sensitive signal transduction pathway." 

PMID- 24658424
TI  - [Do we teach the smoking cessation intervention to future nurses? Result of a
      descriptive study].

PMID- 24658422
TI  - Brain-derived neurotrophic factor/FK506-binding protein 5 genotype by childhood
      trauma interactions do not impact on hippocampal volume and cognitive
      performance.
AB  - In the development of psychotic symptoms, environmental and genetic factors may
      both play a role. The reported association between childhood trauma and psychotic
      symptoms could therefore be moderated by single nucleotide polymorphisms (SNPs)
      associated with the stress response, such as FK506-binding protein 5 (FKBP5) and
      brain-derived neurotrophic factor (BDNF). Recent studies investigating childhood
      trauma by SNP interactions have inconsistently found the hippocampus to be a
      potential target underlying these interactions. Therefore, more detailed
      modelling of these effects, using appropriate covariates, is required. We
      examined whether BDNF/FKBP5 and childhood trauma interactions affected two
      proxies of hippocampal integrity: (i) hippocampal volume and (ii) cognitive
      performance on a block design (BD) and delayed auditory verbal task (AVLT). We
      also investigated whether the putative interaction was different for patients
      with a psychotic disorder (n = 89) compared to their non-psychotic siblings (n =
      95), in order to elicit possible group-specific protective/vulnerability effects.
      SNPs were rs9296158, rs4713916, rs992105, rs3800373 (FKBP5) and rs6265 (BDNF). In
      the combined sample, no BDNF/FKBP5 by childhood trauma interactions were apparent
      for either outcome, and BDNF/FKBP5 by childhood trauma interactions were not
      different for patients and siblings. The omission of drug use and alcohol
      consumption sometimes yielded false positives, greatly affected explained error
      and influenced p-values. The consistent absence of any significant BDNF/FKBP5 by
      childhood trauma interactions on assessments of hippocampal integrity suggests
      that the effect of these interactions on psychotic symptoms is not mediated by
      hippocampal integrity. The importance of appropriate statistical designs and
      inclusion of relevant covariates should be carefully considered. 

PMID- 24658423
TI  - Shear stress induced by an interstitial level of slow flow increases the
      osteogenic differentiation of mesenchymal stem cells through TAZ activation.
AB  - Shear stress activates cellular signaling involved in cellular proliferation,
      differentiation, and migration. However, the mechanisms of mesenchymal stem cell
      (MSC) differentiation under interstitial flow are not fully understood. Here, we
      show the increased osteogenic differentiation of MSCs under exposure to constant,
      extremely low shear stress created by osmotic pressure-induced flow in a
      microfluidic chip. The interstitial level of shear stress in the proposed
      microfluidic system stimulated nuclear localization of TAZ (transcriptional
      coactivator with PDZ-binding motif), a transcriptional modulator of MSCs,
      activated TAZ target genes such as CTGF and Cyr61, and induced osteogenic
      differentiation. TAZ-depleted cells showed defects in shear stress-induced
      osteogenic differentiation. In shear stress induced cellular signaling, Rho
      signaling pathway was important forthe nuclear localization of TAZ. Taken
      together, these results suggest that TAZ is an important mediator of interstitial
      flow-driven shear stress signaling in osteoblast differentiation of MSCs. 

PMID- 24658425
TI  - The critical role of interfacial dynamics in the stability of organic
      photovoltaic devices.
AB  - Understanding the stability and degradation mechanisms of organic solar materials
      is required to achieve long device lifetimes. Here we study photodegradation
      mechanisms of the (poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4
      b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)]):[6,6]-phenyl-C61-butyric acid
      methyl ester (PCPDTBT:PCBM) low band gap-based photovoltaic blend. We apply quasi
      steady state Photo-induced Absorption Optical Spectroscopy, time-resolved
      Electron Spin Resonance Spectroscopy and theoretical modeling to investigate the
      dynamics of long-lived photoexcited species. The role of the interfacial physics
      in the efficiency and robustness of the photovoltaic blend is clarified. We
      demonstrate that the polymer triplet state (T), populated through the interfacial
      charge transfer (CT) state recombination, coexists with charge carriers. However,
      in contrast to previous suggestions, it has no role in the degradation process
      caused by air exposure. Instead, the long-lived emissive interfacial CT state is
      responsible for the blend degradation in air. It mediates direct electron
      transfer to contaminants, leading to the formation of reactive and harmful
      species, such as the superoxide. 

PMID- 24658426
TI  - Ankle-foot orthoses management in children with spastic diplegia: re: day vs. day
      night use of ankle-foot orthoses in young children with spastic diplegia.

PMID- 24658427
TI  - New challenges for the graduate medical educator: implementing the milestones.
AB  - Physical medicine and rehabilitation residency programs will face new challenges
      as they implement the Milestones and establish a Clinical Competency Committee,
      new requirements in the Accreditation Council of Graduate Medical Education's
      Next Accreditation System. The milestones require programs to measure the
      capabilities of individual residents, and programs will be expected to show how
      residents progress to successively higher levels of behavior during the course of
      the residency. Program directors will be assisted by a committee of faculty whose
      role is to assess each individual resident's attainment of milestones and assist
      in the early identification of residents not making the expected progress.
      Programs will need to evaluate their assessment programs and will need to create
      a coherent mix of instruments to evaluate all of the milestones. Because the
      milestones are based on observable behaviors, a key component of this system will
      be direct observation by faculty of residents during patient care. However, many
      faculty are not trained in this skill. Faculty development in observational
      skills, workplace-based assessment skills, and providing formative feedback will
      be a very important aspect if the milestones are to be successfully used to help
      residents make developmental progress in their clinical competence. 

PMID- 24658428
TI  - Non-weight-bearing status compromises the functional level up to 1 yr after hip
      fracture surgery.
AB  - OBJECTIVE: The aim of this study was to examine the influence of weight-bearing
      (WB) status after hip fracture surgery on 1-yr functional outcome. DESIGN: This
      was a prospective cohort study, carried out in a public acute hospital trauma
      service. The 194 patients (36 men and 158 women), with a mean (SD) age of 81.4
      (6.1) yrs, were admitted with a hip fracture within 2009 and were followed for 1
      yr thereafter. The influence of postoperative WB status on the 1-yr functional
      outcome was assessed using the Functional Independence Measure (18-126 points),
      adjusting for other known factors by multiple linear regression. RESULTS: Seventy
      five patients (39%) were not allowed WB for a period of 2-4 wks after surgery.
      Improved functional outcomes were associated positively with prefracture
      functional level and having a trochanteric fracture during the first year after
      fracture (P <= 0.01). Non-WB status, age, health status, and cognitive impairment
      of the patient were associated negatively with the 1-yr functional outcome (P <=
      0.03). Prefracture functional level and non-WB status were the strongest
      determinants of functional level (beta = 0.599 and -0.204, respectively; P <
      0.001). CONCLUSIONS: WB status after surgery, in addition to prefracture
      function, cognitive status, health status, age and fracture type, was found to be
      an independent predictor of the 1-yr functional outcome in hip fracture patients.

PMID- 24658429
TI  - Motor recovery via transcallosal and transpontine fibers in a patient with
      intracerebral hemorrhage.
AB  - Little is known about the motor recovery mechanisms via transcallosal or
      tranpontine fibers in stroke patients. In the current study, an attempt was made
      to demonstrate motor recovery via transcallosal and transpontine fibers in a
      patient with intracerebral hemorrhage using diffusion tensor tractography and
      transcranial magnetic stimulation. A 39-yr-old male patient presented with
      complete weakness of the right extremities at the onset of a left midbrain
      hemorrhage. His motor weakness had shown slow recovery for 4 mos to the point
      that he was able to grasp and release using the right hand. Diffusion tensor
      tractography and transcranial magnetic stimulation were performed at 2 wks and 4
      mos after onset. Discontinuation of the left corticospinal tract below the left
      midbrain was observed on the 2-wk diffusion tensor tractography and no motor
      evoked potential was elicited in the right hand on the 2-wk transcranial magnetic
      stimulation study. Four-month diffusion tensor tractography showed that the
      discontinuation of the left corticospinal tract had not been restored; however, a
      new neural pathway was observed, which originated from the left primary motor
      cortex and descended to the left corticospinal tract at the pons through the
      transcallosal and transpontine fibers. In the 4-mo transcranial magnetic
      stimulation study, the latency of motor evoked potential obtained at the right
      hand by stimulation of the left motor cortex was delayed by 9 msecs, compared
      with the opposite motor evoked potential, which seems to be compatible with
      transcallosal and transpontine conduction time. The results suggest that the
      motor function of the affected extremities in this patient was recovered through
      the transcallosal and transpontine fibers from the left motor cortex. 

PMID- 24658430
TI  - Intraday reliability and sensitivity of four functional ability tests in older
      women.
AB  - Functional tests are commonly used to evaluate the functional ability of older
      individuals; however, intraday reliability and sensitivity are required to enable
      informed decisions on whether repeated trials are necessary and to ensure that
      the values obtained from a single session are a patient's true score. This study
      aimed to investigate the intraday reliability and sensitivity of four commonly
      used functional tests in older individuals. Seventy-one healthy older women (mean
      [SD]: age, 71.7 [7.3] yrs; body mass, 64.8 [10.2] kg; stature, 1.58 [0.07] m)
      performed the 6-m maximum walking speed, timed 8-foot up-and-go, chair sit-and
      reach, and back scratch tests three times in one single session, with 1 min
      between trials. Reliability between all trials was examined using intraclass
      correlation coefficient, and sensitivity was examined using typical error. All
      tests were highly reliable (intraclass correlation coefficient range, 0.89-0.99),
      indicating no need for a familiarization trial. Typical error between trials 2
      and 1 were 0.06 m.s-1, 0.42 s, 1.13 cm, 0.92 cm for the 6-m maximum walking
      speed, timed 8-foot up-and-go, chair sit-and-reach, and back scratch tests,
      respectively. Practitioners should perform two trials to examine whether the
      difference between them is less than the typical error reported here. These
      results should help practitioners ensure that scores obtained from an individual
      from these functional tests are a true reflection of their functional ability
      rather than measurement error.

PMID- 24658431
TI  - Mannan-binding lectin-associated serine protease-2 (MASP-2) deficiency in two
      patients with pulmonary tuberculosis and one healthy control.

PMID- 24658432
TI  - Impaired CTLA-4 responses in COPD are associated with systemic inflammation.

PMID- 24658433
TI  - Cellular and molecular immunopathogenesis of ulcerative colitis.

PMID- 24658434
TI  - Finding a fairy in the forest: ELF4, a novel and critical element of type I
      interferon responses.

PMID- 24658435
TI  - IL-15 trans-presentation regulates homeostasis of CD4(+) T lymphocytes.
AB  - Interleukin-15 (IL-15) is essential for the survival of memory CD8(+) and CD4(+)
      T cell subsets, and natural killer and natural killer T cells. Here, we describe
      a hitherto unreported role of IL-15 in regulating homoeostasis of naive CD4(+) T
      cells. Adoptive transfer of splenocytes from non-obese diabetic (NOD) mice
      results in increased homeostatic expansion of T cells in lymphopenic
      NOD.scid.Il15(-/-) mice when compared to NOD.scid recipients. The increased
      accumulation of CD4(+) T cells is also observed in NOD.Il15(-/-) mice, indicating
      that IL-15-dependent regulation also occurs in the absence of lymphopenia.
      NOD.scid mice lacking the IL-15Ralpha chain, but not those lacking the common
      gamma chain, also show increased accumulation of CD4(+) T cells. These findings
      indicate that the IL-15-mediated regulation occurs directly on CD4(+) T cells and
      requires trans-presentation of IL-15. CD4(+) T cells expanding in the absence of
      IL-15 signaling do not acquire the characteristics of classical regulatory T
      cells. Rather, CD4(+) T cells expanding in the absence of IL-15 show impaired
      antigen-induced activation and IFN-gamma production. Based on these findings, we
      propose that the IL-15-dependent regulation of the naive CD4(+) T-cell
      compartment may represent an additional layer of control to thwart potentially
      autoreactive cells that escape central tolerance, while permitting the expansion
      of memory T cells. 

PMID- 24658437
TI  - Individualism and the extended-self: cross-cultural differences in the valuation
      of authentic objects.
AB  - The current studies examine how valuation of authentic items varies as a function
      of culture. We find that U.S. respondents value authentic items associated with
      individual persons (a sweater or an artwork) more than Indian respondents, but
      that both cultures value authentic objects not associated with persons (a
      dinosaur bone or a moon rock) equally. These differences cannot be attributed to
      more general cultural differences in the value assigned to authenticity. Rather,
      the results support the hypothesis that individualistic cultures place a greater
      value on objects associated with unique persons and in so doing, offer the first
      evidence for how valuation of certain authentic items may vary cross-culturally. 

PMID- 24658436
TI  - Analysis of autofluorescence in polymorphonuclear neutrophils: a new tool for
      early infection diagnosis.
AB  - Diagnosing bacterial infection (BI) remains a challenge for the attending
      physician. An ex vivo infection model based on human fixed polymorphonuclear
      neutrophils (PMNs) gives an autofluorescence signal that differs significantly
      between stimulated and unstimulated cells. We took advantage of this property for
      use in an in vivo pneumonia mouse model and in patients hospitalized with
      bacterial pneumonia. A 2-fold decrease was observed in autofluorescence intensity
      for cytospined PMNs from broncho-alveolar lavage (BAL) in the pneumonia mouse
      model and a 2.7-fold decrease was observed in patients with pneumonia when
      compared with control mice or patients without pneumonia, respectively. This
      optical method provided an autofluorescence mean intensity cut-off, allowing for
      easy diagnosis of BI. Originally set up on a confocal microscope, the assay was
      also effective using a standard epifluorescence microscope. Assessing the
      autofluorescence of PMNs provides a fast, simple, cheap and reliable method
      optimizing the efficiency and the time needed for early diagnosis of severe
      infections. Rationalized therapeutic decisions supported by the results from this
      method can improve the outcome of patients suspected of having an infection. 

PMID- 24658438
TI  - Calcium and vitamin D in the regulation of energy balance: where do we stand?
AB  - There is a pandemic of obesity and associated chronic diseases. Dietary calcium
      and vitamin D have many extra-skeletal roles in human health. In this review we
      have summarized the current understanding of their influence on human energy
      balance by examining the epidemiological, clinical, animal, cellular and
      molecular evidence. We opine that while calcium and vitamin D are functional
      nutrients in the battle against obesity, there is a need for prospective human
      trials to tilt the balance of evidence in favour of these nutrients. 

PMID- 24658439
TI  - Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia
      reperfusion-induced gastric lesions: interaction with protective nitric oxide
      (NO) and calcitonin gene-related peptide (CGRP).
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis
      inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat
      gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of
      reperfusion (R). These I/R animals were pretreated with ADMA with or without the
      combination of L-arginine, calcitonin gene-related peptide (CGRP) or a small dose
      of capsaicin, all of which are known to afford protection against gastric
      lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the
      metabolism of ADMA. In the second series, ADMA was administered to capsaicin
      denervated rats. The area of gastric damage was measured with planimetry, gastric
      blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP
      levels were determined using ELISA and RIA. ADMA significantly increased I/R
      induced gastric injury while significantly decreasing GBF, the luminal NO
      content, and the plasma level of CGRP. This effect of ADMA was significantly
      attenuated by pretreatment with CGRP, L-arginine, capsaicin, or a PGE2 analogue.
      In GW4064 pretreated animals, the I/R injury was significantly reduced and this
      effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA
      was exacerbated in capsaicin-denervated animals with a further reduction of CGRP.
      Plasma levels of IL-10 were significantly decreased while malonylodialdehyde
      (MDA) and plasma TNF-alpha contents were significantly increased by ADMA. In
      conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF,
      which is mediated by a fall in NO and CGRP release, and the enhancement of lipid
      peroxidation and its pro-inflammatory properties.

PMID- 24658440
TI  - P-glycoprotein and drug resistance in systemic autoimmune diseases.
AB  - Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders
      of unknown etiology characterized by a wide range of abnormalities of the immune
      system that may compromise the function of several organs, such as kidney, heart,
      joints, brain and skin. Corticosteroids (CCS), synthetic and biologic
      immunosuppressive agents have demonstrated the capacity to improve the course of
      autoimmune diseases. However, a significant number of patients do not respond or
      develop resistance to these therapies over time. P-glycoprotein (P-gp) is a
      transmembrane protein that pumps several drugs out of the cell, including CCS and
      immunosuppressants; thus, its over-expression or hyper-function has been proposed
      as a possible mechanism of drug resistance in patients with autoimmune disorders.
      Recently, different authors have demonstrated that P-gp inhibitors, such as
      cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp
      expression and or function in SLE, RA and PsA patients. These observations
      suggest that P-gp antagonists could be adopted to revert drug resistance and
      improve disease outcome. The complex inter-relationship among drug resistance, P
      gp expression and autoimmunity still remains elusive. 

PMID- 24658441
TI  - The multiple mechanisms of cell death triggered by resveratrol in lymphoma and
      leukemia.
AB  - Lymphoma and leukemia represent a serious threat to human health and life
      expectancy. Resveratrol is, among the natural-derived chemopreventive molecules,
      one of the most effective and better studied. In this paper the main mechanisms
      of cell death triggered by- or linked to- resveratrol are reviewed and discussed.
      The main focus is on lymphoma and leukemia experimental models where resveratrol
      has been tested and investigated at the cellular, molecular or physiological
      levels. The most relevant in vivo challenges involving resveratrol are also
      reported and analyzed in order to define the key features of this polyphenol and
      the potential for the treatment of hematologic tumors. 

PMID- 24658442
TI  - Investigation into variation of endogenous metabolites in bone marrow cells and
      plasma in C3H/He mice exposed to benzene.
AB  - Benzene is identified as a carcinogen. Continued exposure of benzene may
      eventually lead to damage to the bone marrow, accompanied by pancytopenia,
      aplastic anemia or leukemia. This paper explores the variations of endogenous
      metabolites to provide possible clues for the molecular mechanism of benzene
      induced hematotoxicity. Liquid chromatography coupled with time of flight-mass
      spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to
      investigate the variation of endogenous metabolites in bone marrow cells and
      plasma of male C3H/He mice. The mice were injected subcutaneously with benzene
      (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ
      weights, blood parameters and bone marrow smears were also analyzed. The results
      indicated that benzene caused disturbances in the metabolism of oxidation of
      fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in
      bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma
      and thus might be a common disturbed metabolic pathway induced by benzene in
      multiple organs. This study aims to investigate the underlying molecular
      mechanisms involved in benzene hematotoxicity, especially in bone marrow cells. 

PMID- 24658444
TI  - Atmospheric oxidation mechanism and kinetic studies for OH and NO3 radical
      initiated reaction of methyl methacrylate.
AB  - The mechanism for OH and NO3 radical-initiated oxidation reactions of methyl
      methacrylate (MMA) was investigated by using density functional theory (DFT)
      molecular orbital theory. Geometrical parameters of the reactants, intermediates,
      transition states, and products were fully optimized at the B3LYP/6-31G(d,p)
      level. Detailed oxidation pathways were presented and discussed. The rate
      constants were deduced by the canonical variational transition-state (CVT) theory
      with the small-curvature tunneling (SCT) correction and the multichannel Rice
      Ramspergere-Kassele-Marcus (RRKM) theory, based on the potential energy surface
      profiles over the general atmospheric temperature range of 180-370 K. The
      calculated results were in reasonable agreement with experimental measurement. 

PMID- 24658443
TI  - Bovine induced pluripotent stem cells are more resistant to apoptosis than
      testicular cells in response to mono-(2-ethylhexyl) phthalate.
AB  - Although the androgen receptor (AR) has been implicated in the promotion of
      apoptosis in testicular cells (TSCs), the molecular pathway underlying AR
      mediated apoptosis and its sensitivity to environmental hormones in TSCs and
      induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs
      from bovine TSCs via the electroporation of OCT4. The established iPSCs were
      supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to
      maintain and stabilize the expression of stemness genes and their pluripotency.
      Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate
      (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report
      that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs.
      MEHP also repressed the expression of AR and inactivated WNT signaling, and then
      led to the commitment of cells to apoptosis via the cyclin dependent kinase
      inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were
      responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our
      results suggest that testicular iPSCs can be used to study the signaling pathways
      involved in the response to environmental disruptors, and to assess the toxicity
      of environmental endocrine disruptors in terms of the maintenance of stemness and
      pluripotency. 

PMID- 24658445
TI  - Necrotising enterocolitis in preterm infants: epidemiology and antibiotic
      consumption in the Polish neonatology network neonatal intensive care units in
      2009.
AB  - The aim of this study was to describe the epidemiology of necrotising
      enterocolitis (NEC), antibiotic consumption and the usefulness of microbiological
      tests in very low birth weight (VLBW) Polish newborns. METHODS: Prospective
      surveillance was performed in the year 2009 by local infection control teams. The
      study covered 910 infants hospitalized in six Polish neonatal intensive care
      units. Two kinds of indicators were used for the description of antibiotic usage:
      the duration of treatment (days of treatment, DOTs) and the defined daily dose
      (DDD). RESULTS: NEC incidence was 8.7% and fatality rate was 19%.
      Chorioamnionitis, late gestational age and low birth weight were identified as
      risk factors for NEC. Catheterization, mechanical ventilation and other selected
      procedures were used considerably longer in newborns with NEC than in the
      remaining neonates. Total usage of antibiotics reached 2.9 DDDs or 1.437 days;
      the average use of drugs per case of NEC amounted to 0.47 DDD or 23.2 DOTs. The
      level of antibiotic usage was analysed with correlation to microbiological tests
      performed and it was non-significantly greater in the group of children with NEC
      in whom the tests were performed. CONCLUSIONS: A high risk of developing NEC is
      closely associated with VLBW and with inflammation of the amnion during labour.
      We observed no relationship between the consumption of antibiotics in neonates
      with NEC and positive results of microbiological testing indicating sepsis
      accompanying NEC or gut colonization with pathogens.

PMID- 24658446
TI  - Reply to: Rapid antidepressant effects and abuse  liability of ketamine.

PMID- 24658447
TI  - [Mental health in Colombia].

PMID- 24658448
TI  - Beau's lines secondary to acute illness in an elderly woman.

PMID- 24658449
TI  - All-optical manipulation and probing of the d-f exchange interaction in EuTe.
AB  - We demonstrate that the ultrafast fast dynamics of the d-f exchange interaction,
      between conduction band electrons and lattice spins in EuTe, can be accessed
      using an all-optical technique. Our results reveal, in full detail, the time
      evolution of the d-f exchange interaction induced by a femtosecond laser pulse.
      Specifically, by monitoring the time resolved dynamics of the reflectivity
      changes and Kerr rotation of a weak light pulse reflected from the surface of the
      sample, it is shown that an intense femtosecond light pulse with photon energies
      higher than that of the bandgap, triggers spin waves in EuTe. The laser-induced
      spin waves modulate the d-f exchange interaction, and cause the bandgap to
      oscillate with an amplitude reaching 1 meV, at frequencies up to tens of GHz. The
      ability to control and monitor the dynamics of the exchange energy with our all
      optical technique opens up new opportunities for the manipulation of magnetism at
      ultrafast time-scales.

PMID- 24658450
TI  - In vitro correction of a novel splicing alteration in the BTK gene by using
      antisense morpholino oligonucleotides.
AB  - A novel sequence variant, c.240+109C>A, in the Bruton's tyrosine kinase (BTK)
      gene was identified in a patient with X-linked agammaglobulinemia. This
      alteration resulted in an incorporation of 106 nucleotides of BTK intron 3 into
      its mRNA. Administration of the 25-mer antisense morpholino oligonucleotide
      analog in the patient's cultured peripheral blood mononuclear cells was able to
      restore correctly spliced BTK mRNA, a potential treatment for X-linked
      agammaglobulinemia. 

PMID- 24658451
TI  - Concurrent measurement of dynamic changes in viral load, serum enzymes, T cell
      subsets, and cytokines in patients with severe fever with thrombocytopenia
      syndrome.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection
      caused by a novel Bunyavirus. Analysis on the dynamic changes of clinical,
      laboratory, and immunological abnormalities associated with SFTS in a concurrent
      study is lacking. Thirty-three SFTS patients were admitted to Jiangsu People's
      Hospital, Nanjing, China, and diagnosis was made based on the clinical symptoms
      and positive viral RNA detected by RT-PCR. Four patients deceased and twenty-nine
      survived. Blood samples were collected every other day between Day 5 and Day 15
      from the onset of fever. Samples from healthy volunteers were used as normal
      controls. Peak viral RNA load, serum enzymes, IL-6, and IL-10 were significantly
      higher in deceased patients compared to survivors. Viral load, serum enzymes, and
      cytokines declined in survivors within 2 weeks from onset of fever. CD69+ T cells
      were elevated early after infection while HLA-DR+ and CTLA4+ T cells were
      elevated during the recovery phase of those who survived. High level SFTSV viral
      load was concurrently observed with reduced PLT, elevated serum enzymes, elevated
      pro-inflammatory and anti-inflammatory cytokines, and activation of CD69+ T
      cells. The degree and pattern of changes in these parameters may indicate the
      clinical outcome in SFTSV-infected patients. 

PMID- 24658452
TI  - Effect of partner violence in adolescence and young adulthood on blood pressure
      and incident hypertension.
AB  - Intimate partner violence has adverse health consequences, but little is known
      about its association with hypertension. This study investigates sex differences
      in the relationship between intimate partner violence and blood pressure
      outcomes. Data included 9,699 participants from waves 3 (2001-02) and 4 (2008-09)
      of the National Longitudinal Study of Adolescent Health (51% female). Systolic
      (SBP) and diastolic (DBP) blood pressure and incident hypertension (SBP>=140
      mmHg, DBP>=90 mmHg, or taking antihypertensive medication) were ascertained at
      wave 4. Intimate partner violence was measured at wave 3 with 8 items from the
      revised Conflict Tactics Scales. Separate victimization and perpetration scores
      were calculated. Sex-specific indicators of severe victimization and perpetration
      were created using the 66th percentile among those exposed as a cut point. Sex
      specific, linear and logistic regression models were developed adjusting for age,
      race, financial stress, and education. Thirty-three percent of men and 47% of
      women reported any intimate partner violence exposure; participants were
      categorized as having: no exposure, moderate victimization and / or perpetration
      only, severe victimization, severe perpetration, and severe victimization and
      perpetration. Men experiencing severe perpetration and victimization had a 2.66
      mmHg (95% CI: 0.05, 5.28) higher SBP and a 59% increased odds (OR: 1.59, 95% CI:
      1.07, 2.37) of incident hypertension compared to men not exposed to intimate
      partner violence. No other category of violence was associated with blood
      pressure outcomes in men. Intimate partner violence was not associated with blood
      pressure outcomes in women. Intimate partner violence may have long-term
      consequences for men's hemodynamic health. Screening men for victimization and
      perpetration may assist clinicians to identify individuals at increased risk of
      hypertension. 

PMID- 24658453
TI  - Learning of embodied interaction dynamics with recurrent neural networks: some
      exploratory experiments.
AB  - The new tendency of artificial intelligence suggests that intelligence must be
      seen as a result of the interaction between brains, bodies and environments. This
      view implies that designing sophisticated behaviour requires a primary focus on
      how agents are functionally coupled to their environments. Under this
      perspective, we present early results with the application of reservoir computing
      as an efficient tool to understand how behaviour emerges from interaction.
      Specifically, we present reservoir computing models, that are inspired by
      imitation learning designs, to extract the essential components of behaviour that
      results from agent-environment interaction dynamics. Experimental results using a
      mobile robot are reported to validate the learning architectures. 

PMID- 24658454
TI  - Mice lacking three Loci encoding 14 glutathione transferase genes: a novel tool
      for assigning function to the GSTP, GSTM, and GSTT families.
AB  - Glutathione S-transferases (GSTs) form a superfamily defined by their ability to
      catalyze the conjugation of glutathione with electrophilic substrates. These
      enzymes are proposed to play a critical role in protection of cellular components
      from damage mediated by reactive metabolites. Twenty-two cytosolic GSTs, grouped
      into seven families, are recognized in mice. This complexity hinders the
      assignment of function to a subset or family of these genes. We report generation
      of a mouse line in which the locus encoding three GST gene families is deleted.
      This includes the four Gstt genes spanning 65 kb on chromosome 10 and the seven
      Gstm genes found on a 150 kb segment of DNA chromosome 3. In addition, we delete
      two Gstp genes on chromosome 19 as well as a third related gene located 15 kb
      telomeric to Gstp1 and Gstp2, which we identify as a potential new member of this
      gene family. We show that, despite the loss of up to 75% of total GST activity in
      some tissues from these animals, the mice are healthy and fertile, with normal
      life expectancy. The normal development and health of these animals make them an
      appropriate model for defining the role of these families in redox homeostasis
      and metabolism of drugs and environmental pollutants. 

PMID- 24658455
TI  - Investigational small-molecule drug selectively suppresses constitutive CYP2B6
      activity at the gene transcription level: physiologically based pharmacokinetic
      model assessment of clinical drug interaction risk.
AB  - The glycogen synthase kinase-3 inhibitor LY2090314 specifically impaired CYP2B6
      activity during in vitro evaluation of cytochrome P450 (P450) enzyme induction in
      human hepatocytes. CYP2B6 catalytic activity was significantly decreased
      following 3-day incubation with 0.1-10 MUM LY2090314, on average by 64.3% +/-
      5.0% at 10 MUM. These levels of LY2090314 exposure were not cytotoxic to
      hepatocytes and did not reduce CYP1A2 and CYP3A activities. LY2090314 was not a
      time-dependent CYP2B6 inhibitor, did not otherwise inhibit enzyme activity at
      concentrations <=10 MUM, and was not metabolized by CYP2B6. Thus, mechanism-based
      inactivation or other direct interaction with the enzyme could not explain the
      observed reduction in CYP2B6 activity. Instead, LY2090314 significantly reduced
      CYP2B6 mRNA levels (Imax = 61.9% +/- 1.4%; IC50 = 0.049 +/- 0.043 MUM), which
      were significantly correlated with catalytic activity (r(2) = 0.87, slope = 0.77;
      Imax = 57.0% +/- 10.8%, IC50 = 0.057 +/- 0.027 MUM). Direct inhibition of
      constitutive androstane receptor by LY2090314 is conceptually consistent with the
      observed CYP2B6 transcriptional suppression (Imax = 100.0% +/- 10.8% and 57.1% +/
      2.4%; IC50 = 2.5 +/- 1.2 and 2.1 +/- 0.4 MUM for isoforms 1 and 3, respectively)
      and may be sufficiently extensive to overcome the weak but potent activation of
      pregnane X receptor by <=10 MUM LY2090314 (19.3% +/- 2.2% of maximal rifampin
      response, apparent EC50 = 1.2 +/- 1.1 nM). The clinical relevance of these
      findings was evaluated through physiologically based pharmacokinetic model
      simulations. CYP2B6 suppression by LY2090314 is not expected clinically, with a
      projected <1% decrease in hepatic enzyme activity and <1% decrease in
      hydroxybupropion exposure following bupropion coadministration. However,
      simulations showed that observed CYP2B6 suppression could be clinically relevant
      for a drug with different pharmacokinetic properties from LY2090314. 

PMID- 24658456
TI  - Systemic exposure to the metabolites of lesogaberan in humans and animals: a case
      study of metabolites in safety testing.
AB  - During preclinical and early phase clinical studies of drug candidates, exposure
      to metabolites should be monitored to determine whether safety conclusions drawn
      from studies in animals can be extrapolated to humans. Metabolites accounting for
      more than 10% of total exposure to drug-related material (DRM) in humans are of
      regulatory concern, and for any such metabolites, adequate exposure should be
      demonstrated in animals before large-scale phase 3 clinical trials are conducted.
      We have previously identified six metabolites, M1-M6, of the gastroesophageal
      reflux inhibitor lesogaberan. In this study, we measured exposure in humans,
      rats, and beagle dogs to lesogaberan and these metabolites. Plasma samples were
      taken at various time points after lesogaberan dosing in two clinical and three
      preclinical studies. Concentrations of lesogaberan and its metabolites were
      measured, and exposures during a single dosing interval were calculated. The
      parent compound and metabolites M1, M2, M4, and M5 were together shown to
      constitute all significant exposure to DRM in humans. Only M4 and M5 were present
      at levels of regulatory concern (10.6% and 18.9% of total exposure to DRM,
      respectively, at steady state). Absolute exposure to M5 was greater in rats
      during toxicology studies than the highest absolute exposure observed in humans
      at steady state (117.0 umol * h/liter vs. 52.2 umol * h/liter). In contrast,
      exposure to M4 in rats was less than 50% of the highest absolute exposure
      observed in humans. Further safety testing of this metabolite may therefore be
      required. 

PMID- 24658458
TI  - Axially bonded pentads constructed on the Sn(IV) porphyrin scaffold.
AB  - Three covalently linked dyads such as porphyrin-ferrocene, porphyrin-BODIPY and
      porphyrin-sapphyrin containing one hydroxyphenyl group at the meso-position of
      porphyrin were synthesized by coupling the trans-functionalized porphyrin
      building block, 5-(4-hydroxyphenyl)-10-(4-iodophenyl)-15,20-diphenyl porphyrin,
      with the ethynyl functionalized redox/chromophore building block under mild Pd(0)
      coupling conditions. The dyads were then reacted with SnTTP(OH)2 in benzene in a
      2 : 1 ratio at reflux temperature for 12 hours followed by simple alumina column
      chromatographic purification which afforded three pentads containing three
      different types of redox/chromophore components in 62-80% yields. The pentads are
      very stable and freely soluble in all common organic solvents. The pentads
      formation were confirmed by MALDI-TOF mass spectrometry and 1D and 2D NMR
      studies. Absorption and electrochemical studies suggested that the three
      components in pentads retain their independent characteristic features without
      significant alterations in their properties thus acting like supramolecular
      assemblies. The steady state fluorescence studies indicated a possibility of
      energy/electron transfer among the three types of components in pentads. 

PMID- 24658457
TI  - Habitat specialization along a wetland moisture gradient differs between ammonia
      oxidizing and denitrifying microorganisms.
AB  - Gradients in abiotic parameters, such as soil moisture,can strongly influence
      microbial community structure and function. Denitrifying and ammonia-oxidizing
      microorganisms,in particular, have contrasting physiological responses to abiotic
      factors such as oxygen concentration and soil moisture. Identifying abiotic
      factors that govern the composition and activity of denitrifying and ammonia
      oxidizing communities is critical for understanding the nitrogen cycle.The
      objectives of this study were to (i) examine denitrifier andarchaeal ammonia
      oxidizer community composition and (ii) assess the taxa occurring within each
      functional group related to soil conditions along an environmental gradient. Soil
      was sampled across four transects at four locations along a dry to saturated
      environmental gradient at a restored wetland. Soil pH and soil organic matter
      content increased from dry to saturated plots. Composition of soil denitrifier
      and ammonia oxidizer functional groups was assessed by terminal restriction
      fragment length polymorphism (T-RFLP) community analysis, and local soil factors
      were also characterized. Microbial community composition of denitrifiers and
      ammonia oxidizers differed along the moisture gradient (denitrifier:ANOSIM R =
      0.739, P < 0.001; ammonia oxidizers: ANOSIMR = 0.760, P < 0.001). Individual
      denitrifier taxa were observed over a larger range of moisture levels than
      individual archaeal ammonia oxidizer taxa (Wilcoxon rank sum, W = 2413, P value =
      0.0002). Together, our data suggest that variation in environmental tolerance of
      microbial taxa have potential to influence nitrogen cycling in terrestrial
      ecosystems.

PMID- 24658459
TI  - Self-assembled calixarene aligned patterning of noble metal nanoparticles on
      graphene.
AB  - Patterns of noble metal nanoparticles (NMNPs) of ruthenium and platinum are
      formed on p-phosphonic acid calix[8]arene stabilised graphene in water. This
      involves hydrogen gas induced reduction of metal ions absorbed on the stabilised
      graphene, with TEM revealing the patterns being comprised of domains of parallel
      arrays of NMNPs ~7 nm apart. The domains are orientated in three directions on
      each graphene sheet at an angle of ~60 degrees  or ~120 degrees  with respect to
      each other. AFM of self-assembled p-phosphonic acid calix[8]arene on the surface
      of a highly ordered pyrolytic graphite (HOPG) revealed a similar pattern,
      implying that the orientation of the assembly of p-phosphonic acid calix[8]arene
      is governed by the hexagonal motif of graphite/graphene. 

PMID- 24658460
TI  - Ceria co-doping: synergistic or average effect?
AB  - Ceria (CeO2) co-doping has been suggested as a means to achieve ionic
      conductivities that are significantly higher than those in singly doped systems.
      Rekindled interest in this topic over the last decade has given rise to claims of
      much improved performance. The present study makes use of computer simulations to
      investigate the bulk ionic conductivity of rare earth (RE) doped ceria, where RE
      = Sc, Gd, Sm, Nd and La. The results from the singly doped systems are compared
      to those from ceria co-doped with Nd/Sm and Sc/La. The pattern that emerges from
      the conductivity data is consistent with the dominance of local lattice strains
      from individual defects, rather than the synergistic co-doping effect reported
      recently, and as a result, no enhancement in the conductivity of co-doped samples
      is observed. 

PMID- 24658461
TI  - FISSION1A, an Arabidopsis tail-anchored protein, is localized to three
      subcellular compartments.

PMID- 24658462
TI  - Validation of the V(max) metabolic cart in a simulated pediatric model.
AB  - BACKGROUND: The ability to accurately measure resting energy expenditure (REE)
      using indirect calorimetry, often referred to as the "gold standard" in nutrition
      needs assessment, is important given the well-established positive correlation
      between patient outcome and proportion of the nutrition goal met. While many
      studies have been done to compare various metabolic carts with one another, the
      literature lacks a large simulator-based validation of any metabolic cart system.
      MATERIALS AND METHODS: In the present study, 8 specifically trained staff members
      independently conducted 10 simulation trials each using the V(max) Encore
      metabolic analyzer in conjunction with a metabolic calibration system, which
      simulates patient metabolic activity, to validate the accuracy of the V(max)
      Encore across a wide range of simulated metabolic conditions. Testing conditions
      consisted of incremental adjustments in calibrated gas infusion with a
      consistently set tidal volume and respiratory rate. RESULTS: There was a strong,
      statistically significant correlation between the predicted and actual VO2 and
      VCO2 data (VO2, R (2) = 0.998; VCO2, R (2) = 0.997). In addition, we observed no
      significant difference between individuals performing these trials (VO2, P =
      1.000, F = 0.021, df = 79; VCO2, P = 1.000, F = 0.030, df = 79). CONCLUSIONS:
      This study is the first to report on such a wide spectrum of metabolic activity
      (50-2000 kcal REE) using a calibrated bench model and validates the accuracy,
      reproducibility, and use of the V(max) Encore metabolic cart.

PMID- 24658463
TI  - Underlying mechanism of antimicrobial activity of chitosan microparticles and
      implications for the treatment of infectious diseases.
AB  - The emergence of antibiotic resistant microorganisms is a great public health
      concern and has triggered an urgent need to develop alternative antibiotics.
      Chitosan microparticles (CM), derived from chitosan, have been shown to reduce E.
      coli O157:H7 shedding in a cattle model, indicating potential use as an
      alternative antimicrobial agent. However, the underlying mechanism of CM on
      reducing the shedding of this pathogen remains unclear. To understand the mode of
      action, we studied molecular mechanisms of antimicrobial activity of CM using in
      vitro and in vivo methods. We report that CM are an effective bactericidal agent
      with capability to disrupt cell membranes. Binding assays and genetic studies
      with an ompA mutant strain demonstrated that outer membrane protein OmpA of E.
      coli O157:H7 is critical for CM binding, and this binding activity is coupled
      with a bactericidal effect of CM. This activity was also demonstrated in an
      animal model using cows with uterine diseases. CM treatment effectively reduced
      shedding of intrauterine pathogenic E. coli (IUPEC) in the uterus compared to
      antibiotic treatment. Since Shiga-toxins encoded in the genome of bacteriophage
      is often overexpressed during antibiotic treatment, antibiotic therapy is
      generally not recommended because of high risk of hemolytic uremic syndrome.
      However, CM treatment did not induce bacteriophage or Shiga-toxins in E. coli
      O157:H7; suggesting that CM can be a potential candidate to treat infections
      caused by this pathogen. This work establishes an underlying mechanism whereby CM
      exert antimicrobial activity in vitro and in vivo, providing significant insight
      for the treatment of diseases caused by a broad spectrum of pathogens including
      antibiotic resistant microorganisms. 

PMID- 24658464
TI  - Genome-wide shRNA screen revealed integrated mitogenic signaling between dopamine
      receptor D2 (DRD2) and epidermal growth factor receptor (EGFR) in glioblastoma.
AB  - Glioblastoma remains one of the deadliest of human cancers, with most patients
      succumbing to the disease within two years of diagnosis. The available data
      suggest that simultaneous inactivation of critical nodes within the glioblastoma
      molecular circuitry will be required for meaningful clinical efficacy. We
      conducted parallel genome-wide shRNA screens to identify such nodes and uncovered
      a number of G-Protein Coupled Receptor (GPCR) neurotransmitter pathways,
      including the Dopamine Receptor D2 (DRD2) signaling pathway. Supporting the
      importance of DRD2 in glioblastoma, DRD2 mRNA and protein expression were
      elevated in clinical glioblastoma specimens relative to matched non-neoplastic
      cerebrum. Treatment with independent si-/shRNAs against DRD2 or with DRD2
      antagonists suppressed the growth of patient-derived glioblastoma lines both in
      vitro and in vivo. Importantly, glioblastoma lines derived from independent
      genetically engineered mouse models (GEMMs) were more sensitive to haloperidol,
      an FDA approved DRD2 antagonist, than the premalignant astrocyte lines by
      approximately an order of magnitude. The pro-proliferative effect of DRD2 was, in
      part, mediated through a GNAI2/Rap1/Ras/ERK signaling axis. Combined inhibition
      of DRD2 and Epidermal Growth Factor Receptor (EGFR) led to synergistic
      tumoricidal activity as well as ERK suppression in independent in vivo and in
      vitro glioblastoma models. Our results suggest combined EGFR and DRD2 inhibition
      as a promising strategy for glioblastoma treatment.

PMID- 24658465
TI  - Arterial dysfunction but maintained systemic blood pressure in cavin-1-deficient
      mice.
AB  - Caveolae are omega-shaped plasma membrane micro-domains that are abundant in
      cells of the vascular system. Formation of caveolae depends on caveolin-1 and
      cavin-1 and lack of either protein leads to loss of caveolae. Mice with caveolin
      1 deficiency have dysfunctional blood vessels, but whether absence of cavin-1
      similarly leads to vascular dysfunction is not known. Here we addressed this
      hypothesis using small mesenteric arteries from cavin-1-deficient mice. Cavin-1
      reporter staining was intense in mesenteric arteries, brain arterioles and
      elsewhere in the vascular system, with positive staining of both endothelial and
      smooth muscle cells. Arterial expression of cavin-1, -2 and -3 was reduced in
      knockout (KO) arteries as was expression of caveolin-1, -2 and -3. Caveolae were
      absent in the endothelial and smooth muscle layers of small mesenteric arteries
      as determined by electron microscopy. Arginase, a negative regulator of nitric
      oxide production, was elevated in cavin-1 deficient arteries as was contraction
      in response to the alpha1-adrenergic agonist cirazoline. Detailed assessment of
      vascular dimensions revealed increased media thickness and reduced
      distensibility, arguing that enhanced contraction was due to increased muscle
      mass. Contrasting with increased alpha1-adrenergic contraction, myogenic tone was
      essentially absent and this appeared to be due in part to increased nitric oxide
      production. Vasomotion was less frequent in the knock-out vessels. In keeping
      with the opposing influences on arterial resistance of increased agonist-induced
      contractility and reduced myogenic tone, arterial blood pressure was unchanged in
      vivo. We conclude that deficiency of cavin-1 affects the function of small
      arteries, but that opposing influences on arterial resistance balance each other
      such that systemic blood pressure in unstressed mice is well maintained. 

PMID- 24658467
TI  - Quantifying ant activity using vibration measurements.
AB  - Ant behaviour is of great interest due to their sociality. Ant behaviour is
      typically observed visually, however there are many circumstances where visual
      observation is not possible. It may be possible to assess ant behaviour using
      vibration signals produced by their physical movement. We demonstrate through a
      series of bioassays with different stimuli that the level of activity of meat
      ants (Iridomyrmex purpureus) can be quantified using vibrations, corresponding to
      observations with video. We found that ants exposed to physical shaking produced
      the highest average vibration amplitudes followed by ants with stones to drag,
      then ants with neighbours, illuminated ants and ants in darkness. In addition, we
      devised a novel method based on wavelet decomposition to separate the vibration
      signal owing to the initial ant behaviour from the substrate response, which will
      allow signals recorded from different substrates to be compared directly. Our
      results indicate the potential to use vibration signals to classify some ant
      behaviours in situations where visual observation could be difficult. 

PMID- 24658468
TI  - Prospects for the commercialization of chemiluminescence-based point-of-care and
      on-site testing devices.
AB  - Chemiluminescent reactions have found application in a number of commercial point
      of-care and on-site testing devices. Notable examples include allergy tests
      (e.g., MASTpette, OPTIGEN(r) systems), flu tests (e.g., ZstatFlu(r)-II),
      cartridge-based immunoassay systems (FastPack(r) IP System, PATHFAST(r)),
      forensic tests for bloodstains, portable analyzers for biochip array assays
      (Evidence MultiStat), water quality tests (Eclox), air pollutants (e.g., oxides
      of nitrogen), and handheld devices for detecting explosives (e.g., E3500
      Chemilux(r)). Many other point-of-care or on-site testing devices with a
      chemiluminescent end point have been devised on the basis of a variety of formats
      (e.g., cuvette, cassette, dipstick, test strip, microchip), but most have not
      progressed beyond a proof-of-principle or prototype stage.

PMID- 24658466
TI  - Cross-platform comparison of glycan microarray formats.
AB  - Carbohydrates participate in almost every aspect of biology from protein sorting
      to modulating cell differentiation and cell-cell interactions. To date, the
      majority of data gathered on glycan expression has been obtained via analysis
      with either anti-glycan antibodies or lectins. A detailed understanding of the
      specificities of these reagents is critical to the analysis of carbohydrates in
      biological systems. Glycan microarrays are increasingly used to determine the
      binding specificity of glycan-binding proteins (GBPs). In this study, six
      different glycan microarray platforms with different modes of glycan presentation
      were compared using five well-known lectins; concanavalin A, Helix pomatia
      agglutinin, Maackia amurensis lectin I, Sambucus nigra agglutinin and wheat germ
      agglutinin. A new method (universal threshold) was developed to facilitate
      systematic comparisons across distinct array platforms. The strongest binders of
      each lectin were identified using the universal threshold across all platforms
      while identification of weaker binders was influenced by platform-specific
      factors including presentation of determinants, array composition and self
      reported thresholding methods. This work compiles a rich dataset for comparative
      analysis of glycan array platforms and has important implications for the
      implementation of microarrays in the characterization of GBPs. 

PMID- 24658470
TI  - Computational study of hemodynamic effects of abnormal E/A ratio on left
      ventricular filling.
AB  - Three-dimensional numerical simulations are employed to investigate the
      hemodynamic effects of abnormal E/A ratios on left ventricular filling. The
      simulations are performed in a simplified geometric model of the left ventricle
      (LV) in conjunction with a specified endocardial motion. The model has been
      carefully designed to match the important geometric and flow parameters under the
      physiological conditions. A wide range of E/A ratios from 0 to infinity is
      employed with the aim to cover all the possible stages of left ventricle
      diastolic dysfunction (DD). The effects of abnormal E/A ratios on vortex
      dynamics, flow propagation velocity, energy consumption as well as flow transport
      and mixing are extensively discussed. Our results are able to confirm some common
      findings reported by the previous studies, and also uncover some interesting new
      features.

PMID- 24658469
TI  - Simultaneous determination of aflatoxin B(1), B(2), G(1), G(2), ochratoxin A, and
      sterigmatocystin in traditional Chinese medicines by LC-MS-MS.
AB  - In this paper we describe a rapid, simple, and costeffective liquid
      chromatography-tandem mass spectrometric (LC-MS-MS) method for simultaneous
      analysis of aflatoxin B1, B2, G1, and G2, ochratoxin A, and sterigmatocystin in
      25 traditional Chinese medicines (TCMs). The method is based on single extraction
      with 84:16 (v/v) acetonitrile-water then analysis of the diluted crude extract
      without further clean-up. Chromatographic separation was achieved on a C18
      column, with a mobile phase gradient prepared from aqueous 4 mmol L-1 ammonium
      acetate-0.1 % formic acid and methanol. Quantification of the analytes was by
      selective reaction monitoring (SRM) on a triple-quadrupole mass spectrometer in
      positive-ionization mode. Special focus was on investigating and reducing matrix
      effects to improve accuracy. The established method was validated by
      determination of linearity (r>0.995), sensitivity (limits of quantification 1.6
      25.0 ng L-1), apparent recovery (84.8-110.6 %), extraction recovery (83.6-106.1
      %), and precision (relative standard deviation <=9.9 %) for two representative
      TCMs, Semen Armeniacae Amarae and Radix Pseudostellariae. The applicability of
      the method to TCMs other than these was further investigated, and 23 other TCMs
      with acceptable matrix effects (80.2-118.6 %) were screened. The validated method
      was finally used to assess mycotoxin contamination of 244 samples of 25 TCMs
      collected from local hospitals and TCM pharmacies. Aflatoxin B1 and ochratoxin A
      were detected in 5.3 % of the samples. Sterigmatocystin, the most prevalent
      mycotoxin contaminant, was present in 26.2 % of the samples tested; this has not
      been reported previously. The results of this work imply greater attention should
      be devoted to evaluation of the potential hazard caused by sterigmatocystin in
      TCMs.

PMID- 24658471
TI  - Long-term neuropsychological effects of opioid use in children: a descriptive
      literature review.
AB  - BACKGROUND: Use of opioids in the management of pain and its consequences in
      children presents a substantial challenge. A significant concern in pediatric
      pain management is the long-term neuropsychological consequences of opioids.
      OBJECTIVES: The authors aim to provide a descriptive review of the current
      literature surrounding the neuropsychological impact of opioid use in children,
      along with possible extrapolations from their use in adults and animal models.
      STUDY DESIGN: Systematic review of published literature. SETTING: Various
      universities in the United States. METHODS: The electronic review for papers
      published between January 1992 and December 2012 was conducted using
      Medline/Pubmed, PsychInfo, CINAHL, the Cochrane Library database, and Google
      Scholar. RESULTS: Findings assessing pediatric pain patients treated with opioids
      demonstrated no significant differences in intelligence, behavior, vocabulary, or
      motor skills. One study reported a decrease in a visuo-constructional ability,
      which measured higher order executive function. Studies from prenatal illicit
      opioid exposure found poorer performance on measures of language, verbal ability,
      mathematics, reading, impulse control, and school readiness skills. The
      literature from adult prescribed opioid users has mixed results. Some showed
      impairment in the neuropsychological domains of memory, decision-making,
      attention, concentration, information processing, psychomotor speed, visual
      special skills, and hand-eye coordination, while others found no differences or
      revealed improved perceptual-cognitive status, possibly due to the removal of
      pain as a stressor. LIMITATIONS: Very few studies looked into the long term
      neuropsychological and cognitive effects of the opioids in pediatric population.
      In an attempt to extrapolate from other groups, this review also included
      literature from adult patients, prenatal opioid exposure, and animal studies.
      CONCLUSION: Opioid medications have the potential to produce long-lasting
      neuropsychological side effects. However, given the negative consequences of
      untreated pain, the potential benefit may offset their risk. More studies are
      needed to clarify this complex interaction.

PMID- 24658472
TI  - Timing of neuraxial pain interventions following blood patch for post dural
      puncture headache.
AB  - Post dural puncture headache (PDPH) is a common complication of interventional
      neuraxial procedures. Larger needle gauge, younger patients, low body mass index,
      women (especially pregnant women), and "traumatic" needle types are all
      associated with a higher incidence of PDPH. Currently, an epidural blood patch is
      the gold-standard treatment for this complication. However, despite the high PDPH
      cure rate through the use of this therapy, little is known about the physiology
      behind the success of the epidural blood patch, specifically, the time course of
      patch formation within the epidural space or how long it takes for the blood
      patch volume to be resorbed by the body. Of the many unanswered and debated
      topics related to PDPH and epidural blood patches, one additional specific
      question that may alter clinical management is when it is safe for patients who
      have experienced a disruption of the thecal space and have undergone this
      procedure to have a subsequent epidural or spinal procedure, such as a neuraxial
      anesthetic (i.e. a spinal anesthetic for an elective outpatient procedure) or an
      interventional pain procedure for chronic pain management. This question becomes
      more unclear if the new procedure includes a steroid medication. As an example,
      an older patient presents with a history of lumbar disc disease and during lumbar
      epidural steroid injection, an inadvertent wet tap occurs leading to PDPH.
      Following management with fluids, caffeine, medications, and a successful
      epidural blood patch, it remains unclear as to when would be the best time frame
      to consider a second lumbar epidural steroid injection. We identified the 3 main
      risk factors of subsequent interventional neuraxial procedures as (1) disruption
      of the epidural blood patch and ongoing reparative processes, (2) epidural
      procedure failure, and (3) infection. We looked at the literature, and summarized
      the existing literature in order to enable health care professionals to
      understand the time course of dural repair as well as the risks of subsequent
      neuraxial procedures after epidural blood patches. This review poses the question
      using an evidence based review to discuss the appropriate time course to proceed.

PMID- 24658473
TI  - Short-term treatment with parecoxib for complex regional pain syndrome: a
      randomized, placebo-controlled double-blind trial.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) is characterized by signs and
      symptoms of peripheral inflammation, which leads to peripheral neural
      sensitization associated most frequently (in about 70%) with blunt pressure
      hyperalgesia. Therefore, we hypothesized that treatment of CRPS patients with a
      selective COX-2-inhibitor would alleviate the abnormally low pressure pain
      threshold (PPT) and reduce pain intensity and edema. METHODS: Twenty patients
      with CRPS type I (n = 16) and II of the upper limb and abnormally low PPT were
      double-blind randomised into 2 groups of 10 patients each to receive a 2-day
      intravenous treatment of either 80 mg parecoxib per day (group I) or placebo
      (NaCl 0.9%, group II). Standardized quantitative sensory testing (QST) using the
      DFNS protocol was performed before and after treatment. Pain intensity (NRS 0 -
      10); circumferences of the fingers II, IV, and V (mm); PPT (kPa,
      thenar/hypothenar); and adverse events were recorded daily. STATISTICS: Wilcoxon
      test, Mann-Whitney-U-test, Friedman-test, Fisher-test, significance level: P <
      0.05. STUDY DESIGN: Proof of concept trial performed in randomized, placebo
      controlled, double blind style . SETTING: Pain Management Center in Germany.
      RESULTS: There were no group differences in PTT or other QST parameters. After
      treatment, PPT decreased insignificantly in group I (median [range]; before:
      224.0 [121.0 - 52937] kPa, afterwards: 186.4 [101.4 - 526.5] kPa) and increased
      insignificantly in group II (before: 207.6 [170.0 - 320.5] kPa; afterwards: 235.4
      [163.5 - 349.9] kPa). Pain scores and finger circumferences remained unchanged in
      both groups. LIMITATIONS: Due to difficulty in recruitment the trial was closed
      after inclusion of 20 patients. CONCLUSION: In the present proof-of-concept
      trial, short-term treatment with the selective COX-2-inhibitor parecoxib
      influenced neither PPT nor edema or pain. COX-2 might be less important than
      previously assumed. However, the results are limited due to the small number of
      patients, short-term treatment, and focus on the PPT, which could have led to
      false negative results of the present study and covered the expected therapeutic
      effect.

PMID- 24658474
TI  - Optimal needle entry angle for cervical transforaminal epidural injections.
AB  - BACKGROUND: Cervical epidural steroid injections can be performed through either
      interlaminar or transforaminal approaches, although the interlaminar approach is
      more frequently used, for cervical radicular pain as a result of cervical disc
      herniation or spinal stenosis. Cervical selective nerve root block (CSNRB) is an
      injection that uses a similar approach to that of cervical transforaminal
      epidural steroid injection (CTFESI) but CSNRB is mainly used for diagnostic
      injection, often with local anesthetic only. OBJECTIVE: The aim of this study was
      to investigate an optimal needle entry angle for cervical transforaminal epidural
      steroid injection (CTFESI) or cervical selective nerve root block (CSNRB) using
      the fluoroscopically guided anterior oblique approach. The angle for optimal
      entry into the neuroforamen was measured at various vertebral levels using cross
      sectional cervical spine computed tomography (CT) scans. STUDY DESIGN:
      Retrospective case series analysis. METHODS: From March 2009 to July 2012,
      consecutive patients with presumed discogenic neck pain underwent cervical post
      discography CT scans. The axial images of these CT scans were used to measure the
      optimal angle for needle entry into the neuroforamen. The angles were taken
      bilaterally at levels of C3-4, C4-5, C5-6, C6-7, and C7-T1. The average angle
      between the patient's left and right side was calculated. A total of 190 patients
      were analyzed, including 73 men and 117 women, with ages ranging from 21 to 78
      years old. RESULTS: In both men and women, the mean optimal angle (in degrees)
      with standard deviation measured in the 190 patients at C3-4, C4-5, C5-6, C6-7,
      and C7-T1 were 48 +/- 4, 49 +/- 4, 49 +/- 4, 49 +/- 5, 48 +/- 6, respectively.
      The 95% confidence interval for the true value of the parameter is within 39.84
      to 57.56 degrees. LIMITATIONS: The data for the optimal needle entry angle for
      CTFESI has yet to be tested or confirmed in clinical studies. CONCLUSION: This is
      the first study investigating the optimal needle entry angle for performing
      CTFESIs or CSNRB. Based on a patient population of 190, the optimal entry angle
      using the anterior oblique approach appears to be between the range of 33 to 68
      degrees with an average of slightly less than 50 degrees. Further research with
      angle of needle entry and/or initial fluoroscopic alignment of approximately 50
      degrees in CTFESI or CSNRB is warranted to confirm the usefulness of these
      findings.

PMID- 24658475
TI  - Effect of two contrasting interventions on upper limb chronic pain and
      disability: a randomized controlled trial.
AB  - BACKGROUND: Chronic pain and disability of the arm, shoulder, and hand severely
      affect labor market participation. Ergonomic training and education is the
      default strategy to reduce physical exposure and thereby prevent aggravation of
      pain. An alternative strategy could be to increase physical capacity of the
      worker by physical conditioning. OBJECTIVES: To investigate the effect of 2
      contrasting interventions, conventional ergonomic training (usual care) versus
      resistance training, on pain and disability in individuals with upper limb
      chronic pain exposed to highly repetitive and forceful manual work. STUDY DESIGN:
      Examiner-blinded, parallel-group randomized controlled trial with allocation
      concealment. SETTING: Slaughterhouses located in Denmark, Europe. METHODS: Sixty
      six adults with chronic pain in the shoulder, elbow/forearm, or hand/wrist and
      work disability were randomly allocated to 10 weeks of specific resistance
      training for the shoulder, arm, and hand muscles for 3 x 10 minutes per week, or
      ergonomic training and education (usual care control group). Pain intensity
      (average of shoulder, arm, and hand, scale 0 - 10) was the primary outcome, and
      disability (Work module of DASH questionnaire) as well as isometric shoulder and
      wrist muscle strength were secondary outcomes. RESULTS: Pain intensity,
      disability, and muscle strength improved more following resistance training than
      usual care (P < 0.001, P = 0.05, P <0.0001, respectively [corrected]). Pain
      intensity decreased by 1.5 points (95% confidence interval -2.0 to -0.9)
      following resistance training compared with usual care, corresponding to an
      effect size of 0.91 (Cohen's d). LIMITATIONS: Blinding of participants is not
      possible in behavioral interventions. However, at baseline outcome expectations
      of the 2 interventions were similar. CONCLUSION: Resistance training at the
      workplace results in clinical relevant improvements in pain, disability, and
      muscle strength in adults with upper limb chronic pain exposed to highly
      repetitive and forceful manual work. TRIAL REGISTRATION: NCT01671267.

PMID- 24658476
TI  - A pressure comparison between midline and paramedian approaches to the cervical
      epidural space.
AB  - BACKGROUND: In the cervical spine, the ligamentum flavum (LF) is often
      incompletely fused at the midline. Therefore, accessing the epidural space (ES)
      using the loss of resistance (LOR) technique via the midline approach could be
      less reliable than the paramedian approach. Since the tactile sensation of LOR is
      due to abrupt loss of pressure upon entering the ES, we have compared pressure
      changes between the 2 different cervical epidural techniques. OBJECTIVES: The aim
      of this study was to compare pressure changes during the pathway to the cervical
      ES between the 2 approaches. STUDY DESIGN: A prospective, open-labeled,
      randomized, comparative study. SETTING: An interventional pain management
      practice in a hospital, Republic of Korea. METHODS: The 74 patients were randomly
      assigned to either a midline or paramedian group. The pressure changes were
      monitored and classified into 4 grades according to the following criteria: Grade
      I. The pressure waveform sequence consisted of 3 components in chronological
      order: 1) a high positive pressure just prior to entering the ES; 2) an abrupt
      pressure decrease at the moment of entering the ES; and 3) a negative peak
      pressure before cervical epidural pressure equilibration. Grade II. A high
      positive pressure followed by a precipitous pressure drop, without negative peak
      pressure upon entering the ES. Grade III. High positive pressure before entering
      the ES, followed by continuous pressure decrease without negative pressure. Grade
      IV. No pressure changes before or after entering the cervical ES. RESULTS: An
      abrupt pressure decrease at the moment of exiting the LF or entering the ES was
      more frequently observed when using the paramedian approach (P < 0.05) with the
      odds ratio of 4.96 (95% CI, 1.63 - 15.12) as compared with the midline approach.
      LIMITATIONS: A correlation between the abrupt pressure decrease and LOR tactile
      sensation has been assumed. CONCLUSION: Under the assumption that the LOR
      sensation is due to an abrupt decrease in pressure the moment the needle enters
      the ES or exits the LF, this study claims that the accuracy of accessing the
      cervical ES can be improved significantly using the paramedian approach. CLINICAL
      TRIAL: NCT01009385. Institutional Review Board (IRB): H-1208-107-422.

PMID- 24658477
TI  - The distance from skin to cervical and high thoracic epidural space on chinese
      adults as read from MRI.
AB  - BACKGROUND: A few studies on the depth from the skin to the cervical epidural
      space (DSES) have been reported from the United States, South Korea, Japan, and
      Taiwan. There are no published reports from mainland China. OBJECTIVES: The goal
      of this study was to collect standard data on Chinese adults from mainland China
      in a large medical center with a wide geographical range of patients. STUDY
      DESIGN: A prospective study. SETTING: Department of Anesthesiology, Pain
      Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical
      University. METHODS: The survey included 410 patients. Measurements were made of
      DSES, the dural sac, and the spinal cord by automatic measuring ruler on
      transverse and sagittal images of the cervical spine at the C5-6, C6-7, C7-T1, T1
      2, and T2-3 intervertebral space obtained by magnetic resonance imaging (MRI). We
      also obtained the width of the epidural space by measuring the distance from the
      (LF) to the dural sac. RESULTS: DSES at C5-6, C6-7, C7-T1, T1-2, and T2-3,
      respectively, was 4.69 +/- 0.84 cm, 5.14 +/- 0.98 cm, 5.56 +/- 1.03 cm, 5.81 +/-
      0.94 cm, and 5.76 +/- 0.86 cm on T2W (weighted) MRIs obtained in the sagittal
      plane (mean +/- SD). The distance at C5-6, C6-7, and C7-T1 in transverse images
      was 4.67 +/- 0.86 cm, 5.18 +/- 1.02 cm, and 5.55 +/- 0.97 cm, respectively. All
      measured distances from the skin to the epidural space were significantly greater
      in men than in women. Multivariate regression analysis revealed significant
      partial correlation between DSES and (BMI). LIMITATION: Limitations include the
      absence of healthy individuals as well as the influence of the difference in neck
      positioning during the MRI examination vs. active epidural puncture. CONCLUSION:
      DSES varied with the cervical intervertebral level in those patients studied from
      the population of mainland China. The greatest DSES was noted at C7-T1 in men and
      T1-2 in women, and the least was at C5-6 in both men and women. DSES had a
      significant relationship with neck circumference and BMI in both genders. We
      suggest that the DSES be measured with MRI before performing epidural puncture.
      The lower cervical and upper thoracic intervertebral spaces appear to provide a
      greater margin of safety for epidural puncture.

PMID- 24658478
TI  - The effects of gastroretentive gabapentin (Gralise(r)) on spinal stenosis
      patients with radicular pain.
AB  - BACKGROUND: The health and efficacy profiles of Gralise(r) in the treatment of
      pain from spinal stenosis and radicular symptomatology have not been measured. A
      review of the current literature indicates that no studies exist that evaluate
      the safety and efficacy profiles of Gralise(r) in the treatment of pain from
      spinal stenosis and radicular symptomatology. OBJECTIVE: Our study is aimed at
      determining whether Gralise is a safe and effective pharmacotherapy for the pain
      from spinal stenosis and radicular symptomatology. STUDY DESIGN: A 4-week
      prospective open label single arm and single center study of patients with MRI
      diagnosis of spinal stenosis with radicular pain. METHODS: The primary measure of
      efficacy was a change in average daily pain (ADP) score from baseline to
      completion of Gralise therapy for 4 weeks. The secondary efficacy endpoints were
      the patients' Patients Global Impression of Change Scale (PGIC), the clinician's
      Clinical Global Impression of Change Scale (CGI) reports, and the Medical
      Outcomes Study (MOS) sleep scale of improvement from baseline to completing 4
      weeks of Gralise therapy. The safety and tolerability were evaluated by the
      incidence of adverse events reported while on Gralise therapy. SETTING: The study
      was performed at the Clinical Research Facilities at Tulane Medical Center, New
      Orleans, Louisiana, in the period from December 1, 2012, to August 30, 2013.
      RESULTS: Thirty-five patients achieved an efficacy point of one-week Gralise
      medication treatment. Twenty-seven of 35 (77.2%) patients completed all 5 visits.
      The PGIC noted a significant positive change in: (1) activity limitations; (2)
      symptoms; (3) emotions and overall quality of life when related to their
      condition from first visit as well as improved degree of change when related to
      their condition from first to last visit. The MOS sleep scale and sleep diaries
      noted a significant increase of hours slept on average (an increase in over one
      hour per night--5.8 hours versus 6.86 hours) from the beginning of the study to
      the end. The CGI noted a majority of 10 out of 27 with marked significant
      therapeutic effect with no side effects. The ADP rating from pain intensity scale
      and pain diaries noted significant improvement of lesser levels of pain
      experienced (P =.5907 and P =.8547 respectively). No significant adverse effects
      were noted in the study. LIMITATIONS: Variation in degree of spinal stenosis,
      small sample size. CONCLUSIONS: Gralise demonstrated moderate efficacy with
      reduced pain intensity and increased sleep and was well tolerated in spinal
      stenosis patients with radicular symptoms.

PMID- 24658479
TI  - Prednisolone in complex regional pain syndrome.
AB  - BACKGROUND: Although there are several studies of systemic corticosteroid
      therapies in various doses and various durations in complex regional pain
      syndrome (CRPS), the outcome measurement parameters are limited to the range of
      motion measurements, edema, and symptoms of CRPS. OBJECTIVE: To investigate the
      effects of prednisolone on clinical symptoms, pain, hand grip strength, range of
      motion, as well as on functional ability and quality of life in patients who
      developed CRPS after traumatic upper extremity injury. STUDY DESIGN:
      Retrospective evaluation. METHODS: Forty-five patients who used prednisolone for
      CRPS of the upper extremity were retrospectively studied. Prednisolone was
      started with a dose of 30 mg and tapered by 5 mg every 3 days until
      discontinuation after 3 weeks. Clinical symptoms (morning stiffness, cold
      intolerance, shoulder pain, numbness of fingers, hyperesthesia, abnormal
      sweating, and cyanosis that is exacerbated by exposure to cold temperature), pain
      (Visual Analogue Scale-Rest [VAS-R] and VAS-Activity [VAS-A]) were reviewed. The
      muscle strength with grip strength (GS) (kg), lateral pinch (LP) (pound), tip-to
      tip pinch (TP) (pound), and chuck pinch (CP) (pound) measurements; the joint
      range of motion with using third finger tip-distal crease distance (FT-DC) (cm);
      functional ability with Quick-Disabilities of the Arm, Shoulder and Hand (Q-DASH)
      score; and quality of life with Short Form-36 (SF-36) score were evaluated.
      RESULTS: Mean age was 43.53 +/- 11.43 years. After 3 weeks of therapy, patients
      showed significant improvements in clinical symptoms compared to the basal
      assessments (P < 0.05). The comparison of pre- and post-treatment results
      revealed that VAS-R, VAS-A, GS, LP, TP, CP, FT-DC, Q-DASH scores, and all SF-36
      subscores were significantly improved (P < 0.05). LIMITATIONS: The retrospective
      design and data collection procedure was limited to the medical records of
      patients. CONCLUSION: A short-term oral prednisolone therapy significantly
      reduced the symptoms and signs of CRPS, and improved the functional abilities and
      quality of life.

PMID- 24658480
TI  - The effects of dexmedetomidine alone and in combination with tramadol or
      amitriptyline in a neuropathic pain model.
AB  - BACKGROUND: Interactions between the sympathetic and somatic nervous system play
      an essential role in the pathophysiologic mechanisms of neuropathic pain. The
      alpha2-adrenoceptor agonists produce effective antinociception, but sedation is
      an important adverse effect. Multidrug therapy is potentially valuable to
      decrease side effects. OBJECTIVE: The aim of the present study was to investigate
      the possible antinociceptive effect of dexmedetomidine, an alpha2-adrenoceptor
      agonist, and its combination with front-line treatment of neuropathic pain, i.e.,
      amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the
      sciatic nerve in rats. STUDY DESIGN: Controlled animal study. METHODS: Following
      unilateral ligation of the left sciatic nerve, the effect of intraperitoneal
      (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30
      mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and
      hyperalgesia (measured by Randall and Selitto test) was studied. RESULTS: The
      sham-operated rats and un-operated hind paw (right paw) press normally on the
      floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests
      confirmed the development of neuropathic pain after CCI. All individual drugs and
      dexmedetomidine combination with either tramadol or amitriptyline were effective
      in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine,
      amitriptyline, tramadol, amitriptyline+dexmedetomidine, and
      tramadol+dexmedetomidine combination did not produce any sedation/motor
      impairment (P > 0.05). LIMITATIONS: Although the combination of these drugs
      improved the CCI model of neuropathic pain in this study, an additional
      interpretation of the underlying mechanism(s) will be needed to confirm these
      findings. CONCLUSION: The combination of these drugs appears to be more effective
      in increasing the pain threshold after peripheral nerve injury, when compared
      with the administration of either of amitriptyline or tramadol alone and should
      be considered as a possible alternative to decrease side effects of individual
      drug therapy.

PMID- 24658481
TI  - Acquiring the optimal time for hyperbaric therapy in the rat model of CFA induced
      arthritis.
AB  - BACKGROUND: We previously published an article about the pressure effect using a
      rheumatoid animal model. Hyperbaric therapy appears to be beneficial in treating
      rheumatoid arthritis (RA) by reducing the inflammatory process in an animal
      model. In this sense, acquiring the optimal pressure-treatment time parameter for
      RA is important and no optimal hyperbaric therapy time has been suggested up to
      now. OBJECTIVE: The purpose of our study was to acquire the optimal time for
      hyperbaric therapy in the RA rat model. STUDY DESIGN: Controlled animal study.
      METHODS: Following injection of complete Freund's adjuvant (CFA) into one side of
      the knee joint, 32 rats were randomly assigned to 3 different time groups (1, 3,
      5 hours a day) under 1.5 atmospheres absolute (ATA) hyperbaric chamber for 12
      days. The pain levels were assessed daily for 2 weeks by weight bearing force
      (WBF) of the affected limb. In addition, the levels of gelatinase, MMP-2, and MMP
      9 expression in the synovial fluids of the knees were analyzed. RESULTS: The
      reduction of WBF was high at 2 days after injection and then it was spontaneously
      increased up to 14 days in all 3 groups. There were significant differences of
      WBF between 5 hours and control during the third through twelfth days, between 3
      hours and control during the third through fifth and tenth through twelfth days,
      and between 3 hours and 5 hours during the third through seventh days (P < 0.05).
      The MMP-9/MMP-2 ratio increased at 14 days after the CFA injection in all groups
      compared to the initial findings, however, the 3 hour group showed a smaller MMP
      9/MMP-2 ratio than the control group. LIMITATION: Although enough samples were
      used for the study to support our hypothesis, more samples will be needed to
      raise the validity and reliability. CONCLUSION: The effect of hyperbaric
      treatment appears to be dependent upon the elevated therapy time under 1.5 ATA
      pressure for a short period of time; however, the long-term effects were similar
      in all pressure groups. Further study will be needed to acquire the optimal
      pressure-treatment parameter relationship in various conditions for clinical
      application.

PMID- 24658482
TI  - The disastrous but preventable consequences of ICD-10.

PMID- 24658483
TI  - Assessment of the trends in medical use and misuse of opioid analgesics from 2004
      to 2011.
AB  - BACKGROUND: The epidemic of medical use and abuse of opioid analgesics is linked
      to the economic burden of opioid-related abuse and fatalities in the United
      States. Multiple studies have estimated the extent to which prescription opioid
      analgesics contribute to the national drug abuse problem; studies also assessing
      the trends in medical use and abuse of opioid analgesics have confirmed the
      relationship between increasing medical use of opioids and increasing
      fatalities.The available data is limited until 2002. STUDY DESIGN: Retrospective
      analysis of data from 2004 to 2011 from 2 databases: Automation of Reports and
      Consolidated Orders System (ARCOS) for opioid use data and Drug Abuse Warning
      Network (DAWN) for drug misuse data. OBJECTIVE: To determine the proportion of
      drug abuse related to opioid analgesics and the various trends in the medical use
      and abuse of 8 opioid analgesics commonly used to treat pain: buprenorphine,
      codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and
      oxycodone. METHODS: The data obtained from DAWN is a nationally representative
      sample of hospital emergency department admissions resulting from drug abuse.
      Main outcome measure was the identification of trends in the medical use and
      misuse of opioid analgesics from 2004 to 2011. RESULTS: From 2004 to 2011, there
      was an increase in the medical use of all opioids except for a 20% decrease in
      codeine. The abuse of all opioids including codeine increased during this period.
      Increases in medical use ranged from 2,318% for buprenorphine to 35% for
      fentanyl, including 140% for hydromorphone, 117% for oxycodone, 73% for
      hydrocodone, 64% for morphine, and 37% for methadone. The misuse increased 384%
      for buprenorphine with available data from 2006 to 2011, whereas from 2004 to
      2011, it increased 438% for hydromorphone, 263% for oxycodone, 146% for morphine,
      107% for hydrocodone, 104% for fentanyl, 82% for methadone, and 39% for codeine.
      Comparison of opioid use showed an overall increase of 1,448% from 1996 to 2011,
      with increases of 690% from 1996 to 2004 and 100% from 2004 to 2011. In contrast,
      misuse increased more dramatically: 4,680% from 1996 to 2011, with increases of
      1,372% from 1996 through 2004 and 245% from 2004 to 2011. The number of patients
      seeking rehabilitation for substance abuse also increased 187% for opioids,
      whereas it increased 87% for heroin, 40% for marijuana, and decreased 7% for
      cocaine. LIMITATIONS: Limitations of this assessment include the lack of data
      from 2003, lack of data available on meperidine, and that the aggregate data
      systems used in the study did not identify specific formulations or commercial
      products. CONCLUSION: The present trend of continued increase in the medical use
      of opioid analgesics appears to contribute to increases in misuse, resulting in
      multiple health consequences.

PMID- 24658484
TI  - Percutaneous adhesiolysis procedures in the medicare population: analysis of
      utilization and growth patterns from 2000 to 2011.
AB  - BACKGROUND: Multiple reviews have shown that interventional techniques for
      chronic pain have increased dramatically over the years. Of these interventional
      techniques, both sacroiliac joint injections and facet joint interventions showed
      explosive growth, followed by epidural procedures. Percutaneous adhesiolysis
      procedures have not been assessed for their utilization patterns separately from
      epidural injections. STUDY DESIGN: An analysis of the utilization patterns of
      percutaneous adhesiolysis procedures in managing chronic low back pain in the
      Medicare population from 2000 to 2011. OBJECTIVE: To assess the utilization and
      growth patterns of percutaneous adhesiolysis in managing chronic low back pain.
      METHODS: The study was performed utilizing the Centers for Medicare and Medicaid
      Services (CMS) Physician Supplier Procedure Summary Master of Fee-For-Service
      (FFS) Data from 2000 to 2011. RESULTS: Percutaneous adhesiolysis procedures
      increased 47% with an annual growth rate of 3.6% in the FFS Medicare population
      from 2000 to 2011. These growth rates are significantly lower than the growth
      rates for sacroiliac joint injections (331%), facet joint interventions (308%),
      and epidural injections (130%), but substantially lower than lumbar
      transforaminal injections (665%) and lumbar facet joint neurolysis (544%).
      LIMITATIONS: Study limitations include lack of inclusion of Medicare Advantage
      patients. In addition, the statewide data is based on claims which may include
      the contiguous or other states. CONCLUSION: Percutaneous adhesiolysis utilization
      increased moderately in Medicare beneficiaries from 2000 to 2011. Overall, there
      was an increase of 47% in the utilization of adhesiolysis procedures per 100,000
      Medicare beneficiaries, with an annual geometric average increase of 3.6%.

PMID- 24658485
TI  - Prevalence of chronic pelvic pain among women: an updated review.
AB  - BACKGROUND: Chronic pelvic pain (CPP), defined as a noncyclical pain lasting for
      more than 6 months can lead to lower physical performance and quality of life in
      women. CPP is a worldwide problem affecting women of all ages. However, health
      care professionals and researchers, due to its complex nature and the lack of
      knowledge surrounding the condition, frequently neglect CPP. Subsequently, basic
      data and knowledge regarding CPP remain incomplete. OBJECTIVE: To update the
      review of the worldwide estimation of the CPP prevalence considering the World
      Health Organization systematic review by Latthe et al in 2006 as point of
      departure. STUDY DESIGN: A systematic review of CPP prevalence studies. METHOD:
      Electronic search was performed to find related articles through PubMed between
      2005 and 2012 based on the PRISMA statement (2009). RESULTS: From 140 studies,
      only 7 studies were about CPP prevalence. Their study design consisted of 3 cross
      sectional studies, one population based mailing questionnaire study, one survey
      study (computer assisted telephone interview), one data analysis by
      questionnaire, and one prospective community based study. LIMITATIONS: Paucity of
      population based studies in addition to probability of existence of studies at
      the local level with limited access to worldwide databases, lack of consensus
      about definition of CPP among researchers and therapists, and non-inclusion of
      CPP related key words in databases such as PubMed. CONCLUSION: Based on these
      articles, prevalence in general ranged between 5.7% and 26.6%. There were many
      countries and regions without basic data in the field of CPP. This review shows
      the paucity of studies, especially multidisciplinary researches with
      multifactorial views on CPP. Multidisciplinary studies would provide more
      reliable data for estimating the prevalence of CPP and its psycho-socioeconomic
      burden, as well as finding its etiologies and characteristics. This would be the
      first step towards better treatment and care for women with CPP.

PMID- 24658486
TI  - Nucleoplasty, a minimally invasive procedure for disc decompression: a systematic
      review and meta-analysis of published clinical studies.
AB  - BACKGROUND: Nucleoplasty, based on Coblation(r) technology, is a minimally
      invasive procedure used to decompress herniated discs. Reviews to date-
      exclusively systematic reviews--recommend nucleoplasty for treating chronic back
      pain, although with the restriction of limited to fair evidence. We therefore
      aimed to summarize and interpret our calculated results, where possible
      comprehensively and quantitatively, using statistical methods in the context of a
      meta-analysis supplementing a systematic review. In the process, the central
      question was to statistically determine whether, and to what extent, nucleoplasty
      can positively affect pain relief and functional mobility as well as lower the
      complication rate. OBJECTIVE: Newly published studies made it possible to conduct
      a meta-analysis of the visual analog scale (VAS), a measuring instrument used to
      determine pain intensity, and the Oswestry Disability Index (ODI), a scale that
      reflects the degree of impairment in percent. In addition to having clearly sound
      evidence for analyzing VAS/NPS data, the present, newly compiled meta-analysis
      was able to summarize VAS and ODI data quantitatively and to calculate a total
      complication rate for the first time. It was thereby possible to make a first
      comparison between nucleoplasty and conservative therapy (including epidural
      steroid injection). STUDY DESIGN: This meta-analysis examined all study data
      published in clinical trials involving the nucleoplasty procedure for plasma disc
      decompression. METHODS: A systematic search using the terms nucleoplasty and/or
      plasma disc decompression was conducted for literature listed in MEDLINE. Twenty
      seven eligible studies (22 prospective trials and 5 retrospective trials) were
      included, and pooled analyses as well as various subgroup analyses
      (differentiation between cervical and lumbar disc herniations, comparisons with
      alternative treatments such as epidural steroid injection) were performed based
      on their data. RESULTS: Pain decreased from a baseline VAS value of 7.27 to 2.12
      (postop/first day), 2.50 (one week), 2.70 (2 weeks), 3.23 (one month), 2.66 (6
      weeks), 2.84 (3 months), 3.06 (6 months), 3.03 (12 months), 1.54 (18 months), and
      3.69 (24 months) after nucleoplasty. The ODI value (baseline: 58.95) dropped to
      28.60 (one week), 29.00 (2 weeks), 23.21 (one month), 30.00 (6 weeks), 18.30 (3
      months), 22.54 (6 months), 24.43 (12 months), 12.82 (18 months), and 36.98 (24
      months). Compared to baseline, significant pain reduction and improvement in
      functional mobility after nucleoplasty were observed at every time point.
      Nucleoplasty showed a total complication rate of 1.5%, with the individual rates
      being 0.8% for cervical and 1.8% for lumbar nucleoplasty. Nucleoplasty was
      superior to conservative therapy at every time point and for all 3 included
      parameters, at some measurement time points even significantly. CONCLUSIONS:
      Nucleoplasty reduces pain in the long term and improves patients' functional
      mobility. It is an effective, low-complication, minimally invasive procedure used
      to treat disc herniations.

PMID- 24658487
TI  - The science of conventional and water-cooled monopolar lumbar radiofrequency
      rhizotomy: an electrical engineering point of view.
AB  - Radiofrequency ablation (RFA) is a safe and effective pain therapy used to create
      sensory dysfunction in appropriate nerves via thermal damage. While commonly
      viewed as a simple process, RF heating is actually quite complex from an
      electrical engineering standpoint, and it is difficult for the non-electrical
      engineer to achieve a thorough understanding of the events that occur. RFA is
      highly influenced by the configuration and properties of the peri-electrode
      tissues. To rationally discuss the science of RFA requires that examples be
      procedure-specific, and lumbar RFA is the procedure selected for this review.
      Adequate heating of the lumbar medial branch has many potential failure points,
      and the underlying science is discussed with recommendations to reduce the
      frequency of failure in heating target tissues. Important technical details of
      the procedure that are not generally appreciated are discussed, and the status
      quo is challenged on several aspects of accepted technique. The rationale
      underlying electrode placement and the limitations of RF heating are, for the
      most part, commonly misunderstood, and there may even need to be significant
      changes in how lumbar radiofrequency rhizotomy (RFR) is performed. A new paradigm
      for heating target tissue may be of value. Foremost in developing best practices
      for this procedure is avoiding pitfalls. Good RF heating and medial branch
      lesioning are the rewards for understanding how the process functions, attention
      to detail, and meticulous attention to electrode positioning. 

PMID- 24658488
TI  - Posttraumatic and postsurgical neuropathic pain responsive to treatment with
      capsaicin 8% topical patch.
AB  - Capsaicin 8% patch (Qutenza) is mainly used to treat postherpetic neuralgia and
      human immunodeficiency virus-associated neuropathy. However, evidence of the
      efficacy of Qutenza in other forms of neuropathic pain is lacking. A 24-year old
      Libyan man, with no previous medical history, sustained multiple wounds in the
      right side of the chest and back after a bomb explosion. The patient experienced
      pain, which persisted in a wide location around the surgical intervention for a
      long time, beyond the usual course of natural healing of an acute pain and was
      different from that suffered preoperatively. The characteristics of the pain
      included burning, electric shock-like sensation, tingling, and numbness, and it
      was paroxysmal. The pain was associated with hyperalgesia and intense allodynia
      in a wide area, approximately of 1,100 cm2. Our initial treatment strategy
      included pregabalin, tramadol, and duloxetine. However, our patient's pain
      responded to treatment with capsaicin 8% patch when the initial treatments showed
      only minimal effectiveness regarding the intensity of pain. Interestingly, the
      most important finding was that capsaicin 8% patch showed a more than 80%
      reduction of the area of allodynia associated with the pain, when other
      treatments failed. Moreover, although recent data showed that in patients who
      respond to Qutenza, analgesia starts within a few days of treatment and lasts on
      average 5 months, our patient showed an initial response within 7 days of
      treatment but a longer duration of more than 18 months. Although further
      controlled studies are needed to explore the efficacy of the capsaicin 8% patch
      in patients who experience posttraumatic neuropathic pain, we encourage
      clinicians to try the capsaicin 8% patch when alternative treatments fail. 

PMID- 24658489
TI  - Spinal cord injury from fluoroscopically guided intercostal blocks with phenol.
AB  - BACKGROUND: Image guided intercostal blocks are commonly performed and considered
      relatively safe. Chemical denervation is commonly used in clinical practice for
      treatment of chronic non-cancer associated pain. OBJECTIVE: To report a case of
      spinal cord injury resulting from fluoroscopically guided intercostal blocks with
      phenol. STUDY DESIGN: Case report. SETTING: Inpatient hospital service.
      RESULTS/CASE REPORTS: A 53 year-old women was transferred from her local facility
      for acute onset of lower extremity paresis beginning shortly after right
      intercostal nerve injections of 2 mL of preservative-free phenol at the T7, 8, 9
      levels. She had previous intercostal blocks for chronic right-sided mid
      thoracic/abdominal pain every 3 months for at least one year without sequelae.
      Within 20 minutes of the injection, she developed a sensation of right leg
      weakness and heaviness. Over several hours she developed worsening right leg
      weakness, and then left leg weakness, followed by urinary retention. Admission
      examination revealed severe right greater than left leg weakness, right lower
      extremity hyperesthesia to T10, absent lower extremity reflexes, and bilateral
      extensor plantar responses. Magnetic resonance imaging (MRI) of the entire spine
      demonstrated extensive T2/DWI hyperintensity in the central spinal cord from T1
      to L1 with mild cord enlargement and enhancement at T7-9 (sites of injection).
      Extensive serum and cerebrospinal fluid (CSF) evaluation did not show any
      evidence of an infectious, inflammatory, or metabolic cause to her myelopathy.
      Repeat MRI of the entire spine demonstrated near complete resolution of the T2
      signal abnormality. One month after presentation, despite radiographic
      improvement, the patient showed some clinical improvement, but remained walker
      dependent and with neurogenic bowel and bladder. LIMITATIONS: This report
      describes a single case report. CONCLUSION: This case offers several lessons for
      a pain specialist including 1) the potential for a neurologic catastrophe (spinal
      cord injury) from aqueous neurolytic intercostal blocks despite "safe" contrast
      spread; 2) potential mechanisms of neurogenic injury with intercostal blocks; 3)
      review of modifiable factors to decrease the risk of neurogenic injury; and 4)
      review of potential interventions (steroids, lumbar drain) to improve outcome in
      the setting of iatrogenic procedural related spinal cord injury.

PMID- 24658490
TI  - Opioid induced hyperalgesia altered with propofol infusion.
AB  - Propofol is a common induction agent that is utilized worldwide in the field of
      anesthesiology. In recent years, its potential therapeutic role in a variety of
      patient states has been demonstrated. Controversy exists regarding Propofol
      mediated analgesic and antihyperalgesic properties. Recent studies have suggested
      a variety of different mechanisms of action, including modulation of N-Methyl-D-
      Aspartate receptors and the endocannabinoid system. The N-Methyl-D- Aspartate
      receptor is part of a larger family of glutamate receptors and is an important
      mediator of excitatory neurotransmission. In the case presented, the pain
      experienced by the patient was not well-controlled, in spite of increasing doses
      of opioids, potentially due to superimposed opioid induced hyperalgesia. In the
      present case, we demonstrate a cycle of opioid induced hyperalgesia which was
      successfully affected with a Propofol infusion. Controversial reports exist in
      animal studies on the analgesic properties of Propofol. Randomized controlled
      studies in animal models studying the effect of Propofol on pain sensation have
      shown that Propofol possesses an analgesic effect. This clinical case
      demonstrates that Propofol could possibly have antihyperalgesic effects on opioid
      induced hyperalgesia caused by high-doses of chronic opioids and worsened by
      fentanyl. We postulate that a probable mechanism of complete pain relief after
      the procedure could be the inhibition of activity of the N-Methyl-D- Aspartate
      receptor by Propofol because it was the only agent the patient received during
      the procedure, causing a break of the cycle of opioid induced hyperalgesia.
      Additional research is required to clarify Propofol mediated or modulated
      analgesic properties in humans. 

PMID- 24658491
TI  - Coccyx fractures treated with intranasal calcitonin.
AB  - BACKGROUND: Treating pain associated with acute coccyx fractures can be
      challenging. Intranasal calcitonin has been used to treat acute pain after
      vertebral fracture, and may even accelerate fracture healing. However, intranasal
      calcitonin has never previously been published as part of the treatment of acute
      coccyx fractures. OBJECTIVE: To examine a series of cases in which intranasal
      calcitonin was used to treat coccydynia related to coccyx fractures. STUDY
      DESIGN: Case series and literature review. SETTING: Outpatient university-based
      coccyx pain center. RESULTS: After use of intranasal calcitonin, pain levels
      decreased, adverse events were minimal, and the medication was generally well
      tolerated. LIMITATIONS: As this is not a randomized control trial, the patients
      treated with intranasal calcitonin were not compared to a control group.
      Additionally, the sample size of 8 patients is relatively small. CONCLUSIONS: We
      propose that clinicians consider use of intranasal calcitonin for the treatment
      of pain due to acute coccyx fractures.

PMID- 24658492
TI  - The use of intravenous lidocaine in trigeminal neuralgia pain relief and
      palliative care unit.

PMID- 24658493
TI  - In response.

PMID- 24658494
TI  - Radiation oncologists' response to pundendal entrapment neuropathy.

PMID- 24658495
TI  - Transient brainstem anaesthesia following a diagnostic block for trigeminal
      neuralgia.

PMID- 24658496
TI  - A case of intractable hiccups successfully treated with pregabalin.

PMID- 24658499
TI  - Largazole pharmacokinetics in rats by LC-MS/MS.
AB  - A highly sensitive and specific LC-MS/MS method for the quantitation of largazole
      thiol, the active species of the marine-derived preclinical histone deacetylase
      inhibitor, largazole (prodrug), was developed and validated. Largazole thiol was
      extracted with ethyl acetate from human or rat plasma along with the internal
      standard, harmine. Samples were separated on an Onyx Monolithic C18 column by a
      stepwise gradient elution with 0.1% formic acid in methanol and 0.1% aqueous
      formic acid employing multiple reaction monitoring (MRM) detection. Linear
      calibration curves were obtained in the range of 12.5-400 ng/mL with 200 uL of
      human plasma. The overall intra-day precision was from 3.87% to 12.6%, and the
      inter-day precision was from 7.12% to 9.8%. The accuracy at low, medium and high
      concentrations ranged from 101.55% to 105.84%. Plasma protein bindings of
      largazole thiol in human and rat plasma as determined by an ultrafiltration
      method were 90.13% and 77.14%, respectively. Plasma drug concentrations were
      measured by this LC-MS/MS method. The pharmacokinetics of largazole thiol in rats
      was studied following i.v. administration at 10 mg/kg and found to follow a two
      compartment model. Largazole thiol was rapidly eliminated from systemic
      circulation within 2 h. The established LC-MS/MS method is suitable for the
      analysis of largazole thiol in human plasma, as well.

PMID- 24658500
TI  - Emotional intelligence and mismatching expressive and verbal messages: a
      contribution to detection of deception.
AB  - Processing facial emotion, especially mismatches between facial and verbal
      messages, is believed to be important in the detection of deception. For example,
      emotional leakage may accompany lying. Individuals with superior emotion
      perception abilities may then be more adept in detecting deception by identifying
      mismatch between facial and verbal messages. Two personal factors that may
      predict such abilities are female gender and high emotional intelligence (EI).
      However, evidence on the role of gender and EI in detection of deception is
      mixed. A key issue is that the facial processing skills required to detect
      deception may not be the same as those required to identify facial emotion. To
      test this possibility, we developed a novel facial processing task, the FDT (Face
      Decoding Test) that requires detection of inconsistencies between facial and
      verbal cues to emotion. We hypothesized that gender and ability EI would be
      related to performance when cues were inconsistent. We also hypothesized that
      gender effects would be mediated by EI, because women tend to score as more
      emotionally intelligent on ability tests. Data were collected from 210
      participants. Analyses of the FDT suggested that EI was correlated with superior
      face decoding in all conditions. We also confirmed the expected gender
      difference, the superiority of high EI individuals, and the mediation hypothesis.
      Also, EI was more strongly associated with facial decoding performance in women
      than in men, implying there may be gender differences in strategies for
      processing affective cues. It is concluded that integration of emotional and
      cognitive cues may be a core attribute of EI that contributes to the detection of
      deception. 

PMID- 24658501
TI  - Antidepressant-like effects of auraptenol in mice.
AB  - Depression is a major psychiatric disorder affecting nearly 21% of the world
      population and imposes a substantial health burden on society. Current available
      antidepressants are not adequate to meet the clinical needs. Here we report that
      auraptenol, an active component of the traditional Chinese medicine, angelicae
      dahuricae radix, had antidepressant-like effects in mice models of depression. In
      mouse forced swimming test and tail suspension test, two validated models of
      depression, auraptenol dose-dependently decreased the immobility duration within
      the dose range of 0.05-0.4 mg/kg. In addition, the antidepressant-like effects of
      auraptenol was significantly averted by a selective serotonin 5-HT1A receptor
      antagonist WAY100635 (1 mg/kg). These doses that affected the immobile response
      did not affect locomotor activity. In summary, this study for the first time
      identified an active component from the herbal medicine angelicae dahuricae radix
      that possesses robust antidepressant-like efficacy in mice. These data support
      further exploration for the possibility of developing auraptenol as a novel
      antidepressant agent in the treatment of major depression disorders.

PMID- 24658502
TI  - Zwitterionic borane adducts of N-heterocyclic carbenes from mesomeric betaines of
      uracil.
AB  - We prepared a series of imidazolium-substituted uracil-anions which are members
      of the class of cross-conjugated heterocyclic mesomeric betaines. They are in
      tautomeric equilibrium with their N-heterocyclic carbenes, uracil-6-yl-imidazol-2
      ylidenes. These carbenes can be trapped by reaction with sulfur, selenium, as
      well as by triethylborane and triphenylborane, respectively. The latter trapping
      reaction yielded the first representatives of a new heterocyclic zwitterionic
      ring system, imidazo[2',1':3,4][1,4,2]diazaborolo[1,5-c]pyrimidinium-10-ide.
      Results of two single crystal X-ray structure analyses are presented. 

PMID- 24658503
TI  - Diagnostic yield of the light blue crest sign in gastric intestinal metaplasia: a
      meta-analysis.
AB  - BACKGROUND: The diagnostic yield of light blue crest(LBC) sign, which was
      observed by narrow band imaging with magnification endoscopy(NBI-ME), in
      detecting gastric intestinal metaplasia(IM) has shown variable results.
      OBJECTIVE: We aimed to assess the diagnostic value of LBC under NBI-ME for
      detecting gastric IM. METHODS: We performed a literature search of the
      Medline/PubMed, Embase, Web of Science, Science Direct and the Cochrane Library
      Databases; and a meta-analysis of pooled sensitivity, specificity, positive
      likelihood ratio, negative likelihood ratio, and SROC area under the curve, using
      fixed- and random-effects models, for the accuracy of LBC-based IM diagnosis.
      RESULTS: We initially included 4 articles, but excluded 1 article to counter
      significant heterogeneity. When pooled, the remaining 3 articles, which included
      247 patients with 721 lesions, showed the following patterns in IM diagnosis:
      sensitivity: 0.90 (95% confidence interval [CI] 0.86-0.92); specificity: 0.90
      (95% CI 0.86-0.93), positive likelihood ratio: 8.98 (95% CI 6.42-12.58), negative
      likelihood ratio: 0.12 (95% CI 0.09-0.16), and SROC area under the curve: 0.9560.
      LIMITATIONS: As the studies varied by their definitions for positive LBC,
      endoscopy types, biopsy protocols, race of patient cohort, and physicians'
      proficiency, some sample sizes were limited so that subgroup analyses could not
      be performed. CONCLUSION: We concluded that observing LBC under NBI-ME is an
      accurate and precise means of diagnosing gastric IM.

PMID- 24658505
TI  - Effect of tetracyclines on the development of vascular disease in veterans with
      acne or rosacea: a retrospective cohort study.

PMID- 24658504
TI  - Composition of innate lymphoid cell subsets in the human skin: enrichment of
      NCR(+) ILC3 in lesional skin and blood of psoriasis patients.
AB  - Innate lymphoid cells (ILCs) are increasingly appreciated as important regulators
      of tissue homeostasis and inflammation. However, their role in human skin remains
      obscure. We found that healthy peripheral blood CD117(+) ILC3, lacking the
      natural cytotoxicity receptor (NCR) NKp44 (NCR(-) ILC3), CD117(-)NCR(-)CRTH2(
      )CD161(+) ILC1, and CRTH2(+) ILC2, express the skin-homing receptor cutaneous
      lymphocyte antigen (CLA). NCR(+) ILC3 were scarce in peripheral blood.
      Consistently, we identified in normal skin ILC2 and NCR(-) ILC3, a small
      proportion of CD161(+) ILC1, and hardly any NCR(+) ILC3, whereas NCR(+) ILC3 were
      present in cultured dermal explants. The skin ILC2 and NCR(+) ILC3 subsets
      produced IL-13 and IL-22, respectively, upon cytokine stimulation. Remarkably,
      dermal NCR(-) ILC3 converted to NCR(+) ILC3 upon culture in IL-1beta plus IL-23,
      cytokines known to be involved in psoriatic inflammation. In line with this
      observation, significantly increased proportions of NCR(+) ILC3 were present in
      lesional skin and peripheral blood of psoriasis patients as compared with skin
      and blood of healthy individuals, respectively, whereas the proportions of ILC2
      and CD161(+) ILC1 remained unchanged. NCR(+) ILC3 from skin and blood of
      psoriasis patients produced IL-22, which is regarded as a key driver of epidermal
      thickening, suggesting that NCR(+) ILC3 may participate in psoriasis pathology.

PMID- 24658506
TI  - Wnt5a/beta-catenin signaling drives calcium-induced differentiation of human
      primary keratinocytes.
AB  - It is well established that a gradient of extracellular calcium within the
      epidermis regulates the differentiation of keratinocytes. However, the molecular
      mechanisms implicated in this process are not fully understood. RNA interference
      of the calcium-sensing receptor (CaSR) showed that CaSR is essential in calcium
      induced differentiation of normal human epidermal keratinocytes (NHEKs) by
      increasing the levels of free intracellular calcium, which upregulates the
      expression of Wnt5a but not Wnt3a, Wnt4, and Dkk-1 in the cells. Subsequently,
      autocrine Wnt5a promotes the differentiation of NHEKs, determined by increased
      biosynthesis of keratin-1 and loricrin, whereas proliferation is suppressed.
      Addition of both Wnt5a and calcium to NHEKs activated the Wnt/beta-catenin
      signaling pathway as indicated by (i) increased stability of beta-catenin in the
      cells, (ii) enhanced beta-catenin transcriptional activity, demonstrated by a
      luciferase-based beta-catenin-activated reporter assay, and (iii) augmented
      Wnt/beta-catenin target gene expression. NHEKs depleted for beta-catenin had a
      significantly reduced susceptibility to calcium-induced differentiation.
      Knockdown of axin 2, an antagonist of beta-catenin stability, enhanced the
      biosynthesis of keratin-1 and loricrin in the cells. Our findings establish a
      directional crosstalk between CaSR and Wnt/beta-catenin signaling in keratinocyte
      differentiation via Wnt5a that acts as an autocrine stimulus in this process. 

PMID- 24658507
TI  - Immunological and statistical studies of anti-BP180 antibodies in paraneoplastic
      pemphigus.

PMID- 24658509
TI  - Proinflammatory cytokines and chemokines at the skin interface during Powassan
      virus transmission.

PMID- 24658508
TI  - Hyaluronan metabolism in human keratinocytes and atopic dermatitis skin is driven
      by a balance of hyaluronan synthases 1 and 3.
AB  - Hyaluronan (HA) is a glycosaminoglycan synthesized directly into the
      extracellular matrix by three hyaluronan synthases (HAS1, HAS2, and HAS3). HA is
      abundantly synthesized by keratinocytes but its epidermal functions remain
      unclear. We used culture models to grow human keratinocytes as autocrine
      monolayers or as reconstructed human epidermis (RHE) to assess HA synthesis and
      HAS expression levels during the course of keratinocyte differentiation. In both
      the models, epidermal differentiation downregulates HAS3 mRNA expression while
      increasing HAS1 without significant changes in hyaluronidase expression. HA
      production correlates with HAS1 mRNA expression level during normal
      differentiation. To investigate the regulation of HAS gene expression during
      inflammatory conditions linked to perturbed differentiation, lesional and non
      lesional skin biopsies of atopic dermatitis (AD) patients were analyzed. HAS3
      mRNA expression level increases in AD lesions compared with healthy and non
      lesional skin. Simultaneously, HAS1 expression decreases. Heparin-binding EGF
      like growth factor (HB-EGF) is upregulated in AD epidermis. An AD-like HAS
      expression pattern is observed in RHE incubated with HB-EGF. These results
      indicate that HAS1 is the main enzyme responsible for HA production by normal
      keratinocytes and thus, must be considered as an actor of normal keratinocyte
      differentiation. In contrast, HAS3 can be induced by HB-EGF and seems mainly
      involved in AD epidermis. 

PMID- 24658510
TI  - Skeletal anchorage in the mainstream.

PMID- 24658511
TI  - Retromolar miniscrew implants for Class III camouflage treatment.

PMID- 24658512
TI  - The Rat Trap lingual torquing auxiliary.

PMID- 24658513
TI  - Closure of relapsed spaces with lingual buttons.

PMID- 24658514
TI  - Palatal and mandibular miniscrew implant placement techniques.

PMID- 24658515
TI  - Improved indirect bonding of self-ligating brackets.

PMID- 24658516
TI  - Biocompatibility Assessment of the CentriMag-Novalung Adult ECMO Circuit in a
      Model of Acute Pulmonary Hypertension.
AB  - Extracorporeal membrane oxygenation (ECMO) is rarely used in patients with severe
      pulmonary hypertension (PH) as a bridge to lung transplantation. In this study,
      we assess the blood biocompatibility of the integrated CentriMag-Novalung ECMO
      system (venoarterial) in an acute model of PH. Severe PH (>=2/3 systemic) was
      induced in eight sheep through progressive ligation of the main pulmonary artery.
      System performance, platelet activation, thromboelastography (TEG) parameters,
      fibrinogen, plasma-free hemoglobin, and total plasma protein were measured at
      initiation, 3, and 6 hr of support in the ECMO (N = 4) and sham (N = 4) groups. A
      stable ECMO flow (2.2 +/- 0.1 L/min), low transmembrane pressure gradient, and
      steady blood O2 and CO2 levels were maintained. Platelet activation was low (<4%)
      in both the groups, whereas platelet responsiveness to agonist (platelet
      activating factor) was reduced in the sham group when compared with the ECMO
      group. There were no differences in the TEG parameters, fibrinogen concentration,
      plasma-free hemoglobin (<10 mg/dl), and plasma total protein between the two
      groups. The findings of low levels of platelet activation and plfHb suggest
      adequate blood biocompatibility of the integrated CentriMag-Novalung circuit use
      for short-term support in a model of PH. 

PMID- 24658517
TI  - Safety of parenteral nutrition in patients receiving a ventricular assist device.
AB  - Patients with advanced heart failure and poor nutritional status are predisposed
      to higher rates of infection, bleeding, and mortality. We have increasingly used
      perioperative parenteral nutrition (PN) in ventricular assist device (VAD)
      patients and now report our initial experience. We performed a retrospective
      review of 43 consecutive patients who received implantable VADs from 2006 to
      2009. We compared outcomes for patients receiving PN for >7 days perioperatively
      vs <=7 days. In addition, we compared patients who received preoperative enteral
      nutrition (EN) with those who did not. Fourteen patients received perioperative
      PN in addition to EN for >7 days compared with 29 patients who received either PN
      for <=7 days or EN alone. Univariate analysis showed no differences in infection,
      bleeding, thrombus, stroke, length of stay, or mortality. Multivariate stepwise
      regression including EN, preoperative PN, Interagency Registry for Mechanically
      Assisted Circulation score, age, gender, and VAD indication showed that only EN
      was associated with infection. Prolonged use of perioperative PN appears to be
      safe and well tolerated in patients undergoing VAD implantation. Preoperative EN,
      while increasing infection risk, seems to have no harmful effect on survival. 

PMID- 24658518
TI  - Safety of anticoagulation reversal in patients supported with continuous-flow
      left ventricular assist devices.
AB  - The purpose of this study was to characterize the potential thromboembolic risk
      associated with the reversal of warfarin-based anticoagulation in patients with
      continuous-flow left ventricular assist devices (CF-LVADs). All patients
      implanted with a CF-LVAD between January 1, 2008, and August 1, 2012, at our
      institution were screened, and those who received anticoagulation reversal during
      an inpatient admission were enrolled. The primary outcome is the incidence of
      thrombotic events, including stroke, device thrombosis, or venous thromboembolism
      within 30 days of anticoagulation reversal. Of the 122 patients screened, 25
      patients experienced 38 anticoagulation reversal events. All patients received
      vitamin K at a mean dose of 10 +/- 8 mg, while 60% of patients received fresh
      frozen plasma. Only two patients received prothombin complex concentration and
      three patients received activated factor VII. The rate of thromboembolism within
      30 days of attempted reversal was 2.6% (1/38). This patient developed an ischemic
      stroke after reversal with a high dose of activated factor VII for an acute
      intracranial bleed. The mortality rate within 30 days of reversal was 20% (5/25),
      with three of these deaths associated with acute intracranial hemorrhage.
      Anticoagulation reversal may be safely attempted in selected patients under CF
      LVAD support. 

PMID- 24658519
TI  - Bioabsorbable implant as a tracheal wall substitute in young developing canines.
AB  - This study evaluated a polylactic and polyglycolic acid (PLA/PGA) implant as a
      partial tracheal substitute in young developing canines. This experimental and
      longitudinal study included local stray pups that received substitution of a
      short cervical tracheal segment with a PLA 85%/PGA 15% plaque. We measured
      clinical, endoscopic, and tomographic variables for 1 year, at which time we
      performed histomorphological evaluations of the implant using light and electron
      microscopy. There were no adverse events throughout the clinical progression. On
      endoscopic evaluation, the implant was covered with mucosal tissue beginning in
      the first month, without granulation or stenosis, and the circular shape of the
      trachea was altered. Tomographic images of the tracheal area at the implant site
      were similar to adjacent healthy areas (p = 0.423). At the end of the follow-up
      period, the plaque had biodegraded, and the space was covered by pseudostratified
      epithelium and ciliated cells similar to the neighboring tissue. Implantation of
      a PLA/PGA plaque constituted an effective (functional) replacement of a short
      semicircular cervical tracheal segment without limiting the growth of the
      recipient. Additional studies are required to prove the efficacy of these
      implants for larger tracheal segment replacements and in subjects at different
      stages of development. 

PMID- 24658520
TI  - Absolute blood volume and hepatosplanchnic blood flow measured by indocyanine
      green kinetics during hemodialysis.
AB  - A technique to measure absolute blood volume and hepatosplanchnic blood flow
      (Q(h)) during hemodialysis (HD) is explored. The dispersion and elimination of
      indocyanine green (ICG) were measured using a noninvasive optical device attached
      to the extracorporeal system and compared with transcutaneous measurements.
      Distribution volume (V) and elimination rate constant (k) were determined from
      arterial indicator concentrations assuming standard single-pool behavior. Cardiac
      output (Q(c)) and access flow (Q(a)) were measured by saline dilution technique.
      Duplicate dilutions were available in seven subjects (two female subjects, 78.0
      +/- 9.66 kg dry weight). k was not different between measuring techniques (0.246
      +/- 0.07 vs. 0.249 +/- 0.064 min-1, p = n.s.). V was 4.71 +/- 0.75 L (60.86 +/-
      10.21 ml/kg dry body weight) as anticipated for anthropometric blood volume (p =
      n.s). Indocyanine green half-life was 3.05 +/- 0.89 min and in the range of
      normal liver function. Therefore, ICG clearance (K = kV, 1.14 +/- 0.32 L/min) was
      assumed to correspond to Q(h). Systemic blood flow (Q(s)) calculated as
      difference between Q(c) (7.11 +/- 1.47 L/min) and Q(a) (1.56 +/- 0.88 L/min) was
      5.55 +/- 1.33 L/min. Thus, during HD 21 +/- 5% of Q(s) were consumed by the
      hepatosplanchnic circulation. The analysis of ICG distribution and elimination
      using available online technology for routine HD provides plausible point-of-care
      information, which could be of clinical interests in extracorporeal applications.

PMID- 24658521
TI  - Extracorporeal membrane oxygenation transport after traumatic aortic valve
      injury.
AB  - Traumatic injury to the aortic valve is an uncommon clinical entity. Rarer still
      is the transport of such a patient using extracorporeal membrane oxygenation
      (ECMO) to a specialized ECMO center for definitive repair. We present a case of
      traumatic rupture of the aortic valve complicated by severe acute respiratory
      distress syndrome with interhospital transport using ECMO and subsequent aortic
      valve replacement. 

PMID- 24658522
TI  - Spontaneous retroperitoneal haemorrhage in a young adult.
AB  - We report a rare case of a primary adrenal cortical malignancy presenting with
      spontaneous retroperitoneal haemorrhage in a young adult. To the best of our
      knowledge, this is the thirteenth such case to be reported in the English
      literature. 

PMID- 24658523
TI  - Perforated jejunal diverticulum: a rare presentation of acute abdomen.
AB  - Jejunal diverticulosis is a rare entity with a reported clinical incidence of
      0.5%. However, symptoms relating to its presence are non-specific, which does not
      only delay diagnosis, but also increases the risk of serious complications
      approaching 15%. We report a case of perforated jejunal diverticulum presented
      with a 6-month history of significant weight loss and acute abdominal pain. We
      discuss clinical presentation in both simple and complex cases, diagnostic
      pitfalls and management strategies. 

PMID- 24658524
TI  - Paediatric benign cystic monodermal testicular teratoma.
AB  - We present a case of a painless progressively increasing mass in the left upper
      testis in a 5-year-old boy, which was detected by his father performing
      testicular examination after observing asymmetry of the scrotum. Clinical
      examination, tumour markers, ultrasound scan including colour Doppler studies,
      and finally inguinal exploration and histopathology were helpful in establishing
      the diagnosis of benign cystic monodermal testicular teratoma. Testicular
      teratoma should be considered in the differential diagnosis of any child
      presenting with non-traumatic painless progressive scrotal swelling. Inguinal
      radical orchiectomy is the traditional gold standard treatment for benign
      testicular teratoma in children. Testis-sparing surgery should be reserved for
      smaller testicular tumours known to be benign. 

PMID- 24658525
TI  - Spontaneous ectopic tubal pregnancy after laparoscopic tubal sterilisation by
      segmental isthmic partial salpingectomy.
AB  - A 33-year-old woman with a history of tubal sterilisation, presented to our
      gynaecological emergency unit with acute abdominal pain and signs of peritonism.
      The first day of her last menstruation occurred 4 weeks and 4 days before. Urine
      pregnancy test was positive and transvaginal ultrasound revealed an empty uterus
      with a heterogeneous mass below the right ovary. We performed a laparoscopy,
      which confirmed a previous isthmic partial salpingectomy and the presence of an
      ectopic pregnancy in the right distal remnant tube. Total salpingectomy of the
      remnant parts of the tube was performed and the postoperative course was
      uneventful. 

PMID- 24658526
TI  - Radioactive seed localisation to guide removal of impalpable lymph nodes
      (radioguided occult lesion localisation using iodine-125 seeds, "ROLLIS").
AB  - Two patients with cancer requiring removal of specific impalpable lymph nodes for
      full pathological analysis underwent ultrasound-guided lesion localisation and
      marking with a low-activity I-125 seed. A gamma probe was used in theatre to
      localise the signal from the seed and guide excision. Successful removal of the
      lesions was confirmed with the probe and by specimen radiography. Radioguided
      Occult Lesion Localisation using I-125 Seeds ("ROLLIS") provides a method of
      precisely marking impalpable lesions for surgical excision. 

PMID- 24658527
TI  - Infected total elbow arthroplasty treated by cemented arthrodesis.
AB  - A lady had suffered from deep infection of the GSB III prosthesis of her right
      elbow. The infection could not be controlled by repeated debridement. Finally,
      cemented arthrodesis was performed and the infection was eradicated. 

PMID- 24658528
TI  - Stercoral perforation in a child: a rare complication of NSAID use.
AB  - The adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the
      gastrointestinal (GI) tract are well known. However, NSAID use rarely leads to a
      stercoral perforation, an extremely rare but life-threatening cause of acute
      abdomen. We present a case of stercoral sigmoid colon perforation in a 2-year-old
      girl, secondary to unintentional NSAID overdose, developing as a result of
      miscommunication between the general practitioner (GP) and the mother. To the
      best of our knowledge, stercoral perforation has never before been reported in a
      child. 

PMID- 24658529
TI  - Large retroperitoneal low-grade extraskeletal osteosarcoma.
AB  - Low-grade extraskeletal osteosarcoma is an extremely rare neoplasm with only nine
      cases reported in the literature, in which only one case involved the
      retroperitoneum. Tendency to dedifferentiate as well as recur with high-grade
      variant is known and management principles are not well defined, necessitating a
      continuous review of literature. We report management of the largest such
      retroperitoneal tumour (18.0 cm * 18.3 cm * 17.8 cm) in a 38-year-old man, which
      was treated with surgery followed by six cycles of cisplatin (90 mg/m(2) days 1
      and 2) and doxorubicin (75 mg/m(2) day 3), cycled every 3 weeks (with granulocyte
      colony stimulating factor support as necessary). The patient is disease free
      after 3 years of follow-up.

PMID- 24658531
TI  - Methane storage in metal-organic frameworks.
AB  - Natural gas (NG), whose main component is methane, is an attractive fuel for
      vehicular applications. Realization of safe, cheap and convenient means and
      materials for high-capacity methane storage can significantly facilitate the
      implementation of natural gas fuelled vehicles. The physisorption based process
      involving porous materials offers an efficient storage methodology and the
      emerging porous metal-organic frameworks have been explored as potential
      candidates because of their extraordinarily high porosities, tunable pore/cage
      sizes and easily immobilized functional sites. In this view, we provide an
      overview of the current status of metal-organic frameworks for methane storage. 

PMID- 24658530
TI  - A heuristic model of alcohol dependence.
AB  - BACKGROUND: Substance dependence poses a critical health problem. Sadly, its
      neurobiological mechanisms are still unclear, and this lack of real understanding
      is reflected in insufficient treatment options. It has been hypothesized that
      alcohol effects are due to an imbalance between neuroexcitatory and
      neuroinhibitory amino acids. However, glutamate and GABA interact with other
      neurotransmitters, which form a complicated network whose functioning evades
      intuition and should be investigated systemically with methods of biomedical
      systems analysis. METHODS AND RESULTS: We present a heuristic model of
      neurotransmitters that combines a neurochemical interaction matrix at the
      biochemical level with a mobile describing the balances between pairs of
      neurotransmitters at the physiological and behavioral level. We investigate the
      effects of alcohol on the integrated neurotransmitter systems at both levels. The
      model simulation results are consistent with clinical and experimental
      observations. The model demonstrates that the drug diazepam for symptoms of
      alcohol withdrawal effectively reduces the imbalances between neurotransmitters.
      Moreover, the acetylcholine signal is suggested as a novel target for treatment
      of symptoms associated with alcohol withdrawal. CONCLUSIONS: Efficient means of
      integrating clinical symptoms across multiple levels are still scarce and
      difficult to establish. We present a heuristic model of systemic neurotransmitter
      functionality that permits the assessment of genetic, biochemical, and
      pharmacological perturbations. The model can serve as a tool to represent
      clinical and biological observations and explore various scenarios associated
      with alcohol dependence and its treatments. It also is very well suited for
      educational purposes.

PMID- 24658532
TI  - Acanthamoeba protease activity promotes allergic airway inflammation via protease
      activated receptor 2.
AB  - Acanthamoeba is a free-living amoeba commonly present in the environment and
      often found in human airway cavities. Acanthamoeba possesses strong proteases
      that can elicit allergic airway inflammation. To our knowledge, the
      aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated
      mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra
      nasally and evaluated symptoms and airway immune responses. Acanthamoeba
      trophozoites or ES proteins elicited immune responses in mice that resembled
      allergic airway inflammation. ES proteins had strong protease activity and
      activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP,
      and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl
      methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also
      stimulated dendritic cells and enhanced the differentiation of naive T cells into
      IL-4-secreting T cells. After repeated inoculation of the protease-activated
      receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune
      responses were markedly reduced, but not to basal levels. Furthermore, asthma
      patients had higher Acanthamoeba-specific IgE titers than healthy controls and we
      found Acanthamoeba specific antigen from house dust in typical living room. Our
      findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a
      protease allergen. In addition, it is possible that Acanthamoeba may be one of
      the triggers human airway allergic disease. 

PMID- 24658533
TI  - Prognosis in IgA nephropathy: 30-year analysis of 1,012 patients at a single
      center in Japan.
AB  - BACKGROUND: Little is known about the long-term prognosis of patients with IgA
      nephropathy (IgAN). METHODS: This retrospective cohort analysis evaluated
      clinical and histological findings at the time of renal biopsy, initial
      treatment, patient outcomes over 30 years, and risk factors associated with
      progression in 1,012 patients diagnosed with IgAN at our center since 1974.
      RESULTS: Of the 1,012 patients, 40.5% were male. Mean patient age was 33+/-12
      years and mean blood pressure was 122+/-17/75+/-13 mmHg. Mean serum creatinine
      concentration was 0.89+/-0.42 mg/dL, and mean estimated glomerular filtration
      rate (eGFR) was 78.5+/-26.2 ml/min/1.73 m2. Mean proteinuria was 1.19+/-1.61
      g/day, and mean urinary red blood cells were 36.6+/-35.3/high-powered field.
      Histologically, mesangial hypercellularity was present in 47.6% of patients,
      endothelial hypercellularity in 44.3%, segmental sclerosis in 74.6%, and tubular
      atrophy/interstitial fibrosis in 28.8% by Oxford classification. Initial
      treatment consisted of corticosteroids in 26.9% of patients, renin-angiotensin
      aldosterone system inhibitor in 28.9%, and tonsillectomy plus steroids in 11.7%.
      The 10-, 20-, and 30-year renal survival rates were 84.3, 66.6, and 50.3%,
      respectively. Tonsillectomy plus steroids dramatically improved renal outcome.
      Cox multivariate regression analysis showed that higher proteinuria, lower eGFR,
      and higher uric acid at the time of renal biopsy were independent risk factors
      for the development of end stage renal disease (ESRD). CONCLUSIONS: IgAN is not a
      benign disease, with about 50% of patients progressing to ESRD within 30 years
      despite treatment.

PMID- 24658534
TI  - Multi-locus typing of Histomonas meleagridis isolates demonstrates the existence
      of two different genotypes.
AB  - Histomonas meleagridis is the aetiological agent of histomonosis or "blackhead
      disease". Histomonosis is of special importance today, because there is no
      effective treatment to prevent its occurrence with considerable losses for the
      poultry industry. Despite its importance only a few molecular studies have yet
      been performed to investigate the degree of genetic diversity between different
      isolates of this parasite. In the present study a collection of well defined
      samples, previously shown positive for the DNA of H. meleagridis, was used to
      investigate genetic relatedness of the parasite. Samples originated from 25
      turkey flocks collected in France between 2007 and 2010. Additionally, diagnostic
      samples, collected at our Clinic in Vienna, from different European countries and
      Azerbaijan, during 2010 to 2013 were included in the analyses. For the analysis
      three different genetic loci were analyzed: 18S rRNA, alpha-actinin1 and rpb1
      genes. To amplify partial sequences of alpha-actinin1 and rpb1 genes, primers
      specifically targeting H. meleagridis were designed. Following PCR, the sequences
      of 18S rRNA, alpha-actinin1 and rpb1 loci were analyzed. Phylogenetic analyses
      demonstrated separation of H. meleagridis isolates in two different clusters. The
      majority of isolates grouped within the cluster 1 and originated from different
      European countries. The cluster 2 was rare and predominantly found in samples
      originating from France. Considering that the genetic variability of clusters can
      be seen as two distinct genetic types we propose the term genotype instead of
      cluster. 

PMID- 24658535
TI  - Transmission of chronic wasting disease in Wisconsin white-tailed deer:
      implications for disease spread and management.
AB  - Few studies have evaluated the rate of infection or mode of transmission for
      wildlife diseases, and the implications of alternative management strategies. We
      used hunter harvest data from 2002 to 2013 to investigate chronic wasting disease
      (CWD) infection rate and transmission modes, and address how alternative
      management approaches affect disease dynamics in a Wisconsin white-tailed deer
      population. Uncertainty regarding demographic impacts of CWD on cervid
      populations, human and domestic animal health concerns, and potential economic
      consequences underscore the need for strategies to control CWD distribution and
      prevalence. Using maximum-likelihood methods to evaluate alternative multi-state
      deterministic models of CWD transmission, harvest data strongly supports a
      frequency-dependent transmission structure with sex-specific infection rates that
      are two times higher in males than females. As transmissible spongiform
      encephalopathies are an important and difficult-to-study class of diseases with
      major economic and ecological implications, our work supports the hypothesis of
      frequency-dependent transmission in wild deer at a broad spatial scale and
      indicates that effective harvest management can be implemented to control CWD
      prevalence. Specifically, we show that harvest focused on the greater-affected
      sex (males) can result in stable population dynamics and control of CWD within
      the next 50 years, given the constraints of the model. We also provide a
      quantitative estimate of geographic disease spread in southern Wisconsin,
      validating qualitative assessments that CWD spreads relatively slowly. Given
      increased discovery and distribution of CWD throughout North America, insights
      from our study are valuable to management agencies and to the general public
      concerned about the impacts of CWD on white-tailed deer populations. 

PMID- 24658536
TI  - Label-free characterization of emerging human neuronal networks.
AB  - The emergent self-organization of a neuronal network in a developing nervous
      system is the result of a remarkably orchestrated process involving a multitude
      of chemical, mechanical and electrical signals. Little is known about the dynamic
      behavior of a developing network (especially in a human model) primarily due to a
      lack of practical and non-invasive methods to measure and quantify the process.
      Here we demonstrate that by using a novel optical interferometric technique, we
      can non-invasively measure several fundamental properties of neural networks from
      the sub-cellular to the cell population level. We applied this method to quantify
      network formation in human stem cell derived neurons and show for the first time,
      correlations between trends in the growth, transport, and spatial organization of
      such a system. Quantifying the fundamental behavior of such cell lines without
      compromising their viability may provide an important new tool in future
      longitudinal studies. 

PMID- 24658537
TI  - Nanopore fabrication by controlled dielectric breakdown.
AB  - Nanofabrication techniques for achieving dimensional control at the nanometer
      scale are generally equipment-intensive and time-consuming. The use of energetic
      beams of electrons or ions has placed the fabrication of nanopores in thin solid
      state membranes within reach of some academic laboratories, yet these tools are
      not accessible to many researchers and are poorly suited for mass-production.
      Here we describe a fast and simple approach for fabricating a single nanopore
      down to 2-nm in size with sub-nm precision, directly in solution, by controlling
      dielectric breakdown at the nanoscale. The method relies on applying a voltage
      across an insulating membrane to generate a high electric field, while monitoring
      the induced leakage current. We show that nanopores fabricated by this method
      produce clear electrical signals from translocating DNA molecules. Considering
      the tremendous reduction in complexity and cost, we envision this fabrication
      strategy would not only benefit researchers from the physical and life sciences
      interested in gaining reliable access to solid-state nanopores, but may provide a
      path towards manufacturing of nanopore-based biotechnologies. 

PMID- 24658538
TI  - Winged bean [Psophorcarpus tetragonolobus (L.) DC] seeds as an underutilised
      plant source of bifunctional proteolysate and biopeptides.
AB  - Hypertension is one of the major causes of cardiovascular-related diseases, which
      is highly associated with angiotensin-I-converting enzyme (ACE) activity and
      oxidative stress. In this study, winged bean seed (WBS), a potential source of
      protein, was utilised for the production of bifunctional proteolysate and
      biopeptides with ACE inhibitory and antioxidative properties. An enzymatic
      approach was applied, coupled with pretreatment of shaking and centrifuging
      techniques to remove endogenous ACE inhibitors prior to proteolysis. ACE
      inhibition reached its highest activity, 78.5%, after 12 h proteolysis while
      antioxidative activities, determined using assays involving DPPH radical
      scavenging activity and metal ion-chelating activity, reached peaks of 65.0% and
      65.7% at 8 h and 14 h, respectively. The said bioactivities were proposed to
      share some common structural requirements among peptides. A two-dimensional
      approach was employed for characterisation of effective peptides based on
      hydrophobicity, using RP-HPLC, and isoelectric property, using isoelectric
      focusing technique. Results revealed that acidic and basic peptides with
      partially higher hydrophobicity provided higher ACE inhibition activity than did
      neutral peptides. Finally, by using Q-TOF mass spectrometry, two peptide
      sequences (YPNQKV and FDIRA) with ACE inhibitory and antioxidative activities
      were successfully matched with a database. This study indicates that the WBS
      proteolysate can be a potential bifunctional food ingredient as the identified
      biopeptides demonstrated both ACE inhibitory and antioxidative activities in
      vitro. 

PMID- 24658539
TI  - Excessive nitrite affects zebrafish valvulogenesis through yielding too much NO
      signaling.
AB  - Sodium nitrite, a common food additive, exists widely not only in the environment
      but also in our body. Excessive nitrite causes toxicological effects on human
      health; however, whether it affects vertebrate heart valve development remains
      unknown. In vertebrates, developmental defects of cardiac valves usually lead to
      congenital heart disease. To understand the toxic effects of nitrite on
      valvulogenesis, we exposed zebrafish embryos with different concentrations of
      sodium nitrite. Our results showed that sodium nitrite caused developmental
      defects of zebrafish heart dose dependently. It affected zebrafish heart
      development starting from 36 hpf (hour post fertilization) when heart initiates
      looping process. Comprehensive analysis on the embryos at 24 hpf and 48 hpf
      showed that excessive nitrite did not affect blood circulation, vascular network,
      myocardium and endocardium development. But development of endocardial cells in
      atrioventricular canal (AVC) of the embryos at 48 hpf was disrupted by too much
      nitrite, leading to defective formation of primitive valve leaflets at 76 hpf.
      Consistently, excessive nitrite diminished expressions of valve progenitor
      markers including bmp4, has2, vcana and notch1b at 48 hpf. Furthermore, 3', 5'
      cyclic guanosine monophosphate (cGMP), downstream of nitric oxide (NO) signaling,
      was increased its level significantly in the embryos exposed with excessive
      nitrite and microinjection of soluble guanylate cyclase inhibitor ODQ (1H-[1],
      [2], [4]Oxadiazolo[4,3-a] quinoxalin-1-one), an antagonist of NO signaling, into
      nitrite-exposed embryos could partly rescue the cardiac valve malformation. Taken
      together, our results show that excessive nitrite affects early valve leaflet
      formation by producing too much NO signaling. 

PMID- 24658540
TI  - Selection of higher order regression models in the analysis of multi-factorial
      transcription data.
AB  - INTRODUCTION: Many studies examine gene expression data that has been obtained
      under the influence of multiple factors, such as genetic background,
      environmental conditions, or exposure to diseases. The interplay of multiple
      factors may lead to effect modification and confounding. Higher order linear
      regression models can account for these effects. We present a new methodology for
      linear model selection and apply it to microarray data of bone marrow-derived
      macrophages. This experiment investigates the influence of three variable
      factors: the genetic background of the mice from which the macrophages were
      obtained, Yersinia enterocolitica infection (two strains, and a mock control),
      and treatment/non-treatment with interferon-gamma. RESULTS: We set up four
      different linear regression models in a hierarchical order. We introduce the
      eruption plot as a new practical tool for model selection complementary to global
      testing. It visually compares the size and significance of effect estimates
      between two nested models. Using this methodology we were able to select the most
      appropriate model by keeping only relevant factors showing additional explanatory
      power. Application to experimental data allowed us to qualify the interaction of
      factors as either neutral (no interaction), alleviating (co-occurring effects are
      weaker than expected from the single effects), or aggravating (stronger than
      expected). We find a biologically meaningful gene cluster of putative C2TA target
      genes that appear to be co-regulated with MHC class II genes. CONCLUSIONS: We
      introduced the eruption plot as a tool for visual model comparison to identify
      relevant higher order interactions in the analysis of expression data obtained
      under the influence of multiple factors. We conclude that model selection in
      higher order linear regression models should generally be performed for the
      analysis of multi-factorial microarray data.

PMID- 24658542
TI  - Bipolar electrosurgical vessel-sealing device with compressive force monitoring.
AB  - Bipolar electrosurgical vessel sealing is commonly used in surgery to perform
      hemostasis. The electrode compressive force is demonstrably an important factor
      affecting the vessel seal burst pressure, an index of the seal quality. Using a
      piezoresistive force sensor attached to the handle of a laparoscopic surgical
      device, applied handle force was measured and used to predict the electrosurgical
      vessel compressive force and the pressure at the electrode. The sensor enables
      the monitoring of vessel compressive force during surgery. Four levels of
      compressive force were applied to seal three types of porcine vessels (carotid
      artery, femoral artery, and jugular vein). The burst pressure of the vessel seal
      was tested to evaluate the seal quality. Compressive pressure was found to be a
      statistically significant factor affecting burst pressure for femoral arteries
      and jugular veins. Vessels sealed with low compressive pressure (<300 kPa) have a
      higher failure rate (burst pressure<100 mm Hg) than vessels sealed with high
      compressive pressure. An adequate compressive force is required to generate the
      compressive pressure needed to form a seal with high burst pressure. A
      laparoscopic surgical device with compressive force monitoring capability can
      help ensure adequate compressive pressure, vessel burst pressure, and quality of
      seal.

PMID- 24658541
TI  - The novelty-seeking phenotype modulates the long-lasting effects of intermittent
      ethanol administration during adolescence.
AB  - The aim of the present study was to investigate if a novelty-seeking phenotype
      mediates the long-lasting consequences of intermittent EtOH intoxication during
      adolescence. The hole board test was employed to classify adolescent mice as High
      or Low-Novelty Seekers. Subsequently, animals were administered ethanol (1.25 or
      2.5 g/kg) on two consecutive days at 48-h intervals over a 14-day period. Anxiety
      levels--measured using the elevated plus maze- spontaneous motor activity and
      social interaction test were studied 3 weeks later. A different set of mice
      underwent the same procedure, but received only the 2.5 g/kg dose of ethanol.
      Three weeks later, in order to induce CPP, the same animals were administered 1
      or 6 mg/kg of cocaine or 1 or 2.5 mg/kg MDMA. The results revealed a decrease in
      aggressive behaviors and an anxiolytic profile in HNS mice and longer latency to
      explore the novel object by LNS mice. Ethanol exposure enhanced the reinforcing
      effects of cocaine and MDMA in both groups when CPP was induced with a sub
      threshold dose of the drugs. The extinguished cocaine-induced CPP (1 and 6 mg/kg)
      was reinstated after a priming dose in HNS animals only. Our results confirm that
      intermittent EtOH administration during adolescence induces long-lasting effects
      that are manifested in adult life, and that there is an association between these
      effects and the novelty-seeking phenotype.

PMID- 24658544
TI  - miR-17/20 sensitization of breast cancer cells to chemotherapy-induced apoptosis
      requires Akt1.
AB  - The serine threonine kinase Akt1 has been implicated in the control of cellular
      metabolism, survival and growth. Herein, disruption of the ubiquitously expressed
      member of the Akt family of genes, Akt1, in the mouse, demonstrates a requirement
      for Akt1 in miRNA-mediated cellular apoptosis. The miR-17/20 cluster is known to
      inhibit breast cancer cellular proliferation through G1/S cell cycle arrest via
      binding to the cyclin D1 3'UTR. Here we show that miR-17/20 overexpression
      sensitizes cells to apoptosis induced by either Doxorubicin or UV irradiation in
      MCF-7 cells via Akt1. miR-17/20 mediates apoptosis via increased p53 expression
      which promotes Akt degradation. Akt1-/- mammary epithelial cells which express
      Akt2 and Akt3 demonstrated increased apoptosis to DNA damaging agents. Akt1
      deficiency abolished the miR-17/20-mediated apoptosis. These results demonstrated
      a novel pathway through which miR17/20 regulate p53 and Akt controlling breast
      cancer cell apoptosis.

PMID- 24658543
TI  - TiO2 nanoparticles induced hippocampal neuroinflammation in mice.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) have been used in various medical and
      industrial areas. However, the impacts of these nanoparticles on
      neuroinflammation in the brain are poorly understood. In this study, mice were
      exposed to 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 90 consecutive days, and
      the TLRs/TNF-alpha/NF-kappaB signaling pathway associated with the hippocampal
      neuroinflammation was investigated. Our findings showed titanium accumulation in
      the hippocampus, neuroinflammation and impairment of spatial memory in mice
      following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly activated the
      expression of Toll-like receptors (TLR2, TLR4), tumor necrosis factor-alpha,
      nucleic IkappaB kinase, NF-kappaB-inducible kinase, nucleic factor-kappaB, NF
      kappaB2(p52), RelA(p65), and significantly suppressed the expression of IkappaB
      and interleukin-2. These findings suggest that neuroinflammation may be involved
      in TiO2 NP-induced alterations of cytokine expression in mouse hippocampus.
      Therefore, more attention should be focused on the application of TiO2 NPs in the
      food industry and their long-term exposure effects, especially in the human
      central nervous system. 

PMID- 24658545
TI  - The role of HuR in the post-transcriptional regulation of interleukin-3 in T
      cells.
AB  - Human Interleukin-3 (IL-3) is a lymphokine member of a class of transiently
      expressed mRNAs harboring Adenosine/Uridine-Rich Elements (ARE) in their 3'
      untranslated regions (3'-UTRs). The regulatory effects of AREs are often mediated
      by specific ARE-binding proteins (ARE-BPs). In this report, we show that the
      human IL-3 3'-UTR plays a post-transcriptional regulation role in two human
      transformed cell lines. More specifically, we demonstrate that the hIL-3 3'-UTR
      represses the translation of a luciferase reporter both in HeLa and Jurkat T
      cells. These results also revealed that the hIL-3 3'-UTR-mediated translational
      repression is exerted by an 83 nt region comprised mainly by AREs and some non
      ARE sequences. Moreover, electrophoretic mobility shift assays (EMSAs) and UV
      crosslinking analysis show that this hIL-3 ARE-rich region recruits five specific
      protein complexes, including the ARE-BPs HuR and TIA-1. HuR binding to this ARE
      rich region appears to be spatially modulated during T-cell activation. Together,
      these results suggest that HuR recognizes the ARE-rich region and plays a role in
      the IL-3 3'-UTR-mediated post-transcriptional control in T-cells. 

PMID- 24658546
TI  - High abundance of Escherichia during the establishment of fecal microbiota in
      Brazilian children.
AB  - The sequence of bacterial events that occurs during the colonization of the
      gastrointestinal tract may affect the future health of the host. A clear
      understanding of the colonization process of the human neonatal gut in developing
      countries is lacking because the few available studies were mostly performed
      using culture techniques. Using molecular approaches, this study analyzed the
      fecal microbiota of children of low socioeconomic status in Sao Paulo, Brazil,
      during their first year of life. We collected fecal samples of healthy children
      at 3, 6, and 12 months of life. Total DNA was extracted directly from feces, and
      the bacteria-specific primers 27F-1492R were used to construct 16S rRNA
      libraries. Clones were randomly selected and partially sequenced. The main
      phylogenetic groups identified at 3 months were Streptococcus, unidentified
      bacteria, and Escherichia. At 6 months, Escherichia remained predominant, while
      the unidentified bacterial population increased significantly. At 12 months, a
      more complex composition of fecal microbiota was observed, represented by
      unidentified bacteria and microorganisms found at low rates at earlier ages. The
      genus Escherichia remained the most abundant microorganism (34% relative
      abundance and 75% prevalence). Principal component analysis (PCA) revealed
      changes in the composition of the microbiota at 6 months and an increase of
      diversity at 12 months of life. Bifidobacterium was identified by quantitative
      PCR (qPCR) and showed a high incidence in the microbiota at 3 months. The present
      results corroborate the global observation of inter-individual variability with
      an early establishment of microbial complexity at the end of the first year of
      life and highlight the presence of the Escherichia as abundant in microbiota
      composition of this group of children.

PMID- 24658547
TI  - Surgical management of pancreatic neuroendocrine neoplasms.
AB  - Pancreatic neuroendocrine neoplasms are relatively rare entities, representing
      approximately 1% to 2% of all pancreatic tumors. Owing to their rarity as well as
      their relatively indolent natural history, treatment approaches are not yet
      standardized. A formal pancreatic resection is usually mandatory for large and
      localized sporadic pancreatic tumors or in the presence of symptoms. However, in
      small and asymptomatic lesions, a conservative approach consisting in a careful
      wait-and-see policy is going to appear as more appropriate, particularly when, to
      remove the lesion, an aggressive surgical procedure is required, such as
      pancreaticoduodenectomy or distal splenopancreatectomy, depending on the
      localization of the tumor. Surgery has also a significant role in locally
      advanced and metastatic forms. In the setting of MEN 1 syndrome or Von-Hippel
      Lindau disease, the tumor size and the possible symptoms should be considered in
      the evaluation of a proper treatment.

PMID- 24658548
TI  - Analysis of human herpes virus 6 infections with a quantitative, standardized,
      commercial kit in pediatric stem cell transplant recipients after
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: The aim of the study was to assess the incidence and
      clinical relevance of active Human Herpes Virus 6 (HHV6) infections in pediatric
      patients after allogeneic stem cell transplantation. DESIGN AND SETTINGS:
      Retrospective analysis of samples prospectively collected at Akdeniz University
      Medical Faculty Hospital, Antalya, Turkey, between May 2006 and July 2007 from 15
      pediatric patients with allogeneic hematopoietic stem cell transplantation
      (HSCT). SUBJECTS AND METHODS: A commercial quantitative real-time polymerase
      chain reaction kit was used to analyze plasma samples collected from 15 pediatric
      allogeneic HSCT recipients. RESULTS: HHV6 DNA was found positive in 8 (53%)
      patients. HHV6 DNA levels above 1000 copies/mL were found only in 2 patients and
      they were also consecutively positive for HHV6 DNA. Age at transplantation, use
      of ATG, and receiving grafts other than HLA identical siblings increased the
      risk, with a statistically significant difference, of having HHV6 reactivation
      with levels exceeding 1000 copies/mL (P values, respectively, P=.03, .001, .025).
      Active HHV6 infections with HHV6 viremia levels higher than 1000 copies/mL were
      associated with subsequent delayed platelet engraftment (P=.001), acute graft
      versus host disease (P=.001), skin rash, and fever of unknown origin. CONCLUSION:
      More than half of pediatric allogeneic HSCT patients develop active HHV6
      infection, and especially in patients with high viremic loads, the infection can
      result in serious clinical situations. A clinically significant cutoff value for
      viremia seems to be necessary to predict serious clinical complications.

PMID- 24658549
TI  - The relationship between monoamine oxidase B (MAOB) A644G polymorphism and
      Parkinson disease risk: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Many studies were conducted to assess the relationship
      between Monoamine oxidase B (MAOB) A644G polymorphism and susceptibility to
      Parkinson disease (PD). However, the results were inconsistent and inconclusive.
      DESIGN AND SETTINGS: A meta-analysis was conducted from all published studies on
      the associations between monoamine oxidase B (MAOB) A644G polymorphism and
      Parkinson disease. METHODS: In this present study, the possible relationship
      between MAOB A644G polymorphism and PD risk was assessed by a meta-analysis.
      Eligible articles were identified for the period up to March 2013. Pooled odds
      ratios (OR) with 95% confidence intervals (CI) were appropriately derived from
      fixed-effects models. RESULTS: Twenty case-control studies with a total of 2846
      cases and 3508 controls were eligible. In a recessive model, MAOB A644G
      polymorphism was associated with PD risk (OR=1.32, 95% CI 1.18-1.47, P < .001).
      Subgroup analyses by ethnicity and gender also found significant relationships
      between this polymorphism and PD risk. CONCLUSION: This meta-analysis suggested
      that MAOB A644G polymorphism may be associated with PD development.

PMID- 24658550
TI  - Venoarterial modified ultrafiltration versus conventional arteriovenous modified
      ultrafiltration during cardiopulmonary bypass surgery.
AB  - BACKGROUND AND OBJECTIVES: Different types of modified ultrafiltration (MUF)
      systems evaluated showed that none of the MUF techniques adhered to the normal
      venous to arterial blood flow dynamics. This study compared a conventional
      arteriovenous modified ultrafiltration (AVMUF) system to a custom- designed
      venoarterial modified ultrafiltration (VAMUF) system. DESIGN AND SETTINGS:
      Randomized, controlled clinical study conducted at the Northwest Armed Forces
      Military hospital in Tabuk, Saudi Arabia. PATIENTS AND METHODS: Sixty patients
      who underwent MUF during the years 2007 and 2009 were divided into 2 groups: the
      AVMUF (n=30) and the VAMUF (n=30) groups. MUF was performed for a mean time of 12
      minutes in both groups. In AVMUF, blood was removed from the aorta,
      hemoconcentrated, and infused into the right atrium (RA). In VAMUF, blood flow
      was from the RA through a hemoconcentrator and re-infused into the aorta.
      RESULTS: Results of the study showed that the VAMUF group required a shorter
      ventilation time (P < .001), in.tensive care unit (ICU) (P=.003), and hospital
      stay (P=.007) than the AVMUF group. Results also demonstrated a lower percentage
      of fluid balance (P=.008) in the VAMUF group. The systolic (P < .001) and mean
      blood pres.sures (P < .001) were significantly higher after VAMUF, with a
      decrease in heart rate (P < .001) and central venous pressure (P=.002). The VAMUF
      group showed a significantly greater decrease of creatinine (P < .001), serum
      lactacte (P < .001), and uric acid (P < .027) over time with no significant
      differences in oximetry. CONCLUSION: Results prove that VAMUF is a more
      physiological technique than AVMUF.

PMID- 24658551
TI  - Causes and patterns of spine trauma in children and adolescents in Saudi Arabia:
      implications for injury prevention.
AB  - BACKGROUND AND OBJECTIVES: Knowledge regarding traumatic spine injuries (TSIs) is
      essential for effective prevention strategies, particularly in the developing
      world, where majority of the population is younger and organized prevention
      programs are scarce. Therefore, our objective was to describe TSI mechanisms,
      demographics, patterns, and outcomes in children and adolescents. DESIGN AND
      SETTINGS: Retrospective chart review in a major trauma center from May 2001 to
      May 2009 in Riyadh, Saudi Arabia. PATIENTS AND METHODS: Detailed chart reviews
      were done for all consecutive TSI patients <=18 years old.Cases were identified
      through the trauma database registry that included admitted patients. RESULTS: Of
      the 3796 cases identified, 120 cases (3.2%) sustained 141 TSIs (mean age: 13.5
      years; males:83.8%). TSI was most common among children from 16 to 18 years old.
      Overall, motor vehicle collision (MVC)was the most common injury mechanism
      (60.8%). However, younger patients (<12 years) sustained more pedestrian injuries
      (40.6%). Among MVC cases with known seat belt statuses (43.8%), 90.6% were not
      wearing seat belts. The cervical spine level was the most commonly affected
      (55.8%) region, especially in children <12 years old (88%). More than 1 affected
      spinal level was found in 23.3% cases. Spinal cord injuries were found in 19.2%
      cases. Overall, mortality was 8.3%, and half of these mortalities were secondary
      to pedestrian injuries. A total of 22.7% of cases were discharged with
      neurological deficits. CONCLUSION: The high frequency and severity of MVC and
      pedestrian injuries observed in the present study raise significant concerns
      regarding the safety of children on the roads. Spine involvement was age
      specific;younger patients tended to have more cervical injuries, and older
      patients exhibited more thoracic spine involvement.

PMID- 24658552
TI  - Absence of obesity paradox in Saudi patients admitted with acute coronary
      syndromes: insights from SPACE registry.
AB  - BACKGROUND AND OBJECTIVES: To describe the distribution of body mass index (BMI)
      and its relationship with clinical features, management, and in-hospital outcomes
      of patients admitted with acute coronary syndromes (ACS). DESIGN AND SETTINGS:
      The Saudi Project for Assessment of Coronary Events is a prospective registry.
      ACS patients admitted to 17 hospitals from December 2005-2007 were included in
      this study. METHODS: BMI was available for 3469 patients (68.6%) admitted with
      ACS and categorized into 4 groups: normal weight, overweight, obese, and morbidly
      obese. RESULTS: Of patients admitted with ACS, 72% were either overweight or
      obese. A high prevalence of diabetes (57%), hypertension (56.6%), dyslipidemia
      (42%), and smoking (32.4%) was reported. Increasing BMI was significantly
      associated with diabetes, hypertension, and hyperlipidemia. Overweight and obese
      patients were significantly younger than the normal-weight group (P=.006).
      However, normal-weight patients were more likely to be smokers and had 3-vessel
      coronary artery disease, worse left ventricular dysfunction, and ST elevation
      myocardial infarction. Glycoprotein IIb-IIIa antagonists were used significantly
      more in overweight, obese, and morbidly obese ACS patients than in normal-weight
      patients (P<=.001). Coronary angiography and percutaneous intervention were
      reported more in overweight and obese patients than in normal-weight patients
      (P<=.001). In-hospital outcomes were not significantly different among the BMI
      categories. CONCLUSION: High BMI is prevalent among Saudi patients with ACS. BMI
      was not an independent factor for in-hospital outcomes. In contrast with previous
      reports, high BMI was not associated with improved outcomes, indicating the
      absence of obesity paradox observed in other studies.

PMID- 24658554
TI  - Evaluation of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS)
      for cerebral cavernous malformations: a 15-year single-center experience.
AB  - BACKGROUND AND OBJECTIVES: Surgery is the principal treatment for safely
      accessible hemorrhagic and symptomatic cavernous malformations. Nevertheless, the
      role of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in the
      management of high-risk, symptomatic cavernoma lesions warrants further
      refinement. In this study, we evaluate the use of LINAC-based SRS for cerebral
      cavernous malformations (CMs) and report our 15-year single-center experience.
      DESIGN AND SETTINGS: A retrospective study from the Department of Radiation
      Oncology and the Department of Neurosurgery at Gulhane Military Medical Academy
      and Medical Faculty, Ankara from April 1998 to June 2013. PATIENTS AND METHODS:
      Fifty-two patients (22 females and 30 males) with cerebral CM referred to our
      department underwent high-precision single-dose SRS using a LINAC with 6-MV
      photons. All patients had at least 1 bleeding episode prior to radiosurgery along
      with related symptoms. Median dose prescribed to the 85% to 95% isodose line
      encompassing the target volume was 15 Gy (range, 10-20). RESULTS: Out of the
      total 52 patients, follow-up data were available for 47 patients (90.4%). Median
      age was 35 years (range, 19-63). Median follow-up time was 5.17 years (range,
      0.08-9.5) after SRS. Three hemorrhages were identified in the post-SRS period.
      Statistically significant decrease was observed in the annual hemorrhage rate
      after radiosurgical treatment (pre-SRS 39% vs post-SRS 1.21, P < .0001). Overall,
      there were no radiosurgery-related complications resulting in mortality.
      CONCLUSION: LINAC-based SRS may be considered as a treatment option for high
      risk, symptomatic cerebral CM of selected patients with prior bleeding from
      lesions located at surgically inaccessible or eloquent brain areas.

PMID- 24658553
TI  - Cardiometabolic risk among Saudi children and adolescents: Saudi childrens
      overweight, obesity, and lifestyles (S.Ch.O.O.Ls) study.
AB  - BACKGROUND AND OBJECTIVES: Diabetes and atherosclerotic cardiovascular disease
      are major contributors to the global burden of disease, with a high reported
      prevalence of risk factors among different populations. Early and efficient
      assessment of cardiometabolic risk is important to identify target groups for
      preventive interventions. The aims of Saudi children's overweight, obesity, and
      lifestyles study were to estimate the prevalence of the metabolic syndrome and to
      compare the different paradigms of assessing such risk among children and
      adolescents. The study was funded by National Guard Health Affairs and approved
      by the ethics committee. DESIGN AND SETTINGS: A cross-sectional study of students
      from primary, middle, and secondary schools located in the residential areas for
      the Saudi National Guard employees in Riyadh. METHODS: A random sample of 2149
      students, clustered by school and stratified by grade, was selected from a
      sampling frame of 16 812 students from 10 schools in the residential areas for
      Saudi National Guard employees. Informed consent was taken from children and
      parents. Blood pressure, height, weight, waist circumference, and hip
      circumference were documented. Fasting blood samples were taken for blood glucose
      and lipid profile. RESULTS: The prevalence of metabolic syndrome ranged from 2%
      to 18%, according to the sensitivity of the 6 different definitions. Systolic
      blood pressure and triglycerides-to-HDL (high-density lipoprotein) ratio showed a
      dose-response increase with the quartiles of waist circumference and body mass
      index (BMI). Assessment of cardiometabolic risk by diagnosing the metabolic
      syndrome would lead to missed opportunity of intervention in 94% to 95% of
      children identified to be in need of intervention by waist circumference and BMI
      above 75th percentile. CONCLUSION: Relying on the diagnosis of the metabolic
      syndrome can harm primary preventive initiatives. BMI and waist circumference for
      age should be used for assessing cardiometabolic risk in children and
      adolescents.

PMID- 24658555
TI  - E-health: effect on health system efficiency of Pakistan.
AB  - BACKGROUND AND OBJECTIVES: The health system in Pakistan is spraining because of
      increasing cost and demand gravities. The shortage of skilled health care workers
      is one of the main factors of health issues. There is a need to move away from
      the dependency of tools such as pen, paper, and human memory to a milieu where
      patients and health care providers can reliably access and share health
      information in real time across geographic and health sector boundaries. DESIGN
      AND SETTINGS: The purpose of this research is to observe the effect of e-health
      on the physician-patient relationship and to analyze the capacity of health
      professionals by noting information and communication technologies usage as
      indicators. METHODS: Structured questionnaire was used to gather data from
      physicians to judge the success and effect of existing e-health policy. Both
      categorical and Likert scale variables were used. The analysis of data was
      per.formed using chi-square test and binary logistic regression. RESULTS:
      Specialist doctors comprised the major proportion of health care professionals in
      both male and female categories with good knowledge about Internet usage. E
      health-based communication does not seem to be gender specific. Logistic
      regression revealed that busy doctors whose patients are more than 100 per week
      believe that e-health would significantly strengthen their communication with
      patients (OR=3.06; 95% CI=1.05- 8.87). Among other significant impacts of e
      health include reduced consultation period and time of diagnosis. CONCLUSION: E
      health technology can play a crucial role in controlling many epidemic diseases
      through effective surveillance. E-health implementation will result in improving
      the efficiency, better access of general public to the health care system, and
      eradication of diseases in Pakistan.

PMID- 24658556
TI  - Nasal bone length in Saudi rhinoplasty: a clinical-radiological study.
AB  - BACKGROUND AND OBJECTIVES: Hump reduction in the presence of short nasal bones
      can result in significant esthetic and/or functional problems in patients seeking
      rhinoplasty in the Middle East. The aims of this study were to determine the mean
      length of nasal bones, amount of nasal dorsum it forms in relation to the whole
      nose, and incidence of short nasal bones in the Middle Eastern population. DESIGN
      AND SETTINGS: A prospective study that has been carried out in a tertiary care
      hospital. PATIENTS AND METHODS: A total of 154 patients (80 females and 74 males)
      who were scheduled for computed tomography scan for the paranasal sinuses were
      included in the study. The inclusion criteria were adults with no history of
      facial/nasal trauma, sinus space occupying lesions, or surgery. RESULTS: In
      males, the mean clinical nasal bone length was 19.59 mm and the mean radiological
      nasal bone length was 24.96 mm. In females, the mean clinical nasal bone length
      was 18.17 mm and the mean radiological bone length was 22.82 mm. CONCLUSION: The
      bony vault represents 44.2% of the female nose and 44.3% of the male nose. In the
      present study, no patients displayed a short nasal bone that was less than one
      third of the whole nasal length.

PMID- 24658557
TI  - Prevalence of endobronchial metastases in lung cancer in Scotland.
AB  - BACKGROUND AND OBJECTIVES: Endobronchial metastases are reported in patients
      suffering from lung cancer. The objective of this study was to determine the
      prevalence of this lesion in patients in Scotland. DESIGN AND SETTINGS: Lung
      cancer patients autopsied personally at the Western Infirmary, Glasgow, Scotland,
      were examined regarding the primary lesion and its secondaries with special
      reference to the submucosa of the bronchus. PATIENTS AND METHODS: A total of 100
      patients had full records of their illness and the autopsy findings. RESULTS:
      Four patients had lobectomy and were excluded from the series. Of the remaining
      96 patients, 53 showed no endobronchial metastases, 26 exhibited bronchial
      sheathing, 10 manifested submucosal metastases, and the remaining 7 had both
      sheathing and submucosal metastases. CONCLUSION: This study demonstrated that
      Scottish patients dying with lung cancer displayed endobronchial metastases at
      autopsy. This lesion and its benign counterparts are increasingly undergoing
      therapeutic management.

PMID- 24658558
TI  - Mimicking pancreatic malignancy: a systemic sarcoidosis.
AB  - Systemic sarcoidosis that initially presents as a pancreatic mass has rarely been
      reported. A 47-year-old man presented with idiopathic epigastric abdominal pain.
      Abdominal CT showed multiple enlarged lymph nodes in the retroperitoneal area and
      a suspected tumor mass in the pancreatic head region. The preliminary diagnosis
      was celiac metastasis of a pancreatic malignancy. The definitive diagnosis was
      systemic sarcoidosis, which was supported by granulomas on histology, clinical
      radiographic findings, and clinical response to steroids. A review of published
      reports on sarcoidosis presenting initially as a pancreatic or celiac mass from
      the Chinese biomedical database (1978-2010) is included.

PMID- 24658559
TI  - Pentalogy of Cantrell: first case reported in Saudi Arabia.
AB  - Pentalogy of Cantrell (PC) is a rare congenital anomaly involving defects in the
      anterior diaphragm, supraumbilical abdominal wall, diaphragmatic pericardium, and
      lower sternum, and other congenital intracardiac abnormalities. Here, we report
      the case of a newborn infant who was born at 32 weeks of gestation and had all 5
      features of PC, in addition to absent kidneys and a deformed left hand. Medical
      intervention would not be able to save the patient, so we allowed her to die in
      peace. We discuss here the etiology, prenatal diagnosis, and severity of and the
      mortality associated with this condition. To our knowledge, this was the first
      reported case of PC in Saudi Arabia.

PMID- 24658560
TI  - Cochlear implant and thiamine-responsive megaloblastic anemia syndrome.
AB  - Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive
      disorder defined by the occurrence of megaloblastic anemia, diabetes mellitus,
      and bilateral sensorineural deafness, responding in varying degrees to thiamine
      treatment. We report a precedence case for the treatment of deafness associated
      with the typical triad of thiamine-responsive megaloblastic anemia in a 4-year
      old boy who showed a poor use of preoperative hearing aids but demonstrated
      significant improvements in hearing ability 1 year after receiving a cochlear
      implant.

PMID- 24658561
TI  - Congenital hepatic fibrosis in a child with Prader-Willi syndrome: a novel
      association.
AB  - Prader-Willi syndrome (PWS) is a rare genetic disorder caused by deletion or
      unexpression of the chromosome 15 (q 11-13). Symptomatologies include hypotonia,
      hyperphagia, cognitive impairment, and characteristic dysmorphic profile. Here,
      we report a 4-year-old boy with PWS who presented with complications of
      congenital hepatic fibrosis. The uniparental heterodisomy makes it unlikely that
      the hepatic fibrosis was caused by unmasking of a recessive mutation on the
      maternal chromosome 15 although we cannot exclude the possibility of a
      recessively inherited mutation elsewhere given the parental consanguinity. This
      is the first report of congenital hepatic fibrosis in PWS.

PMID- 24658562
TI  - A rare cause of left atrial mass: endometrial stromal sarcoma metastasis.
AB  - Endometrial stromal sarcomas (ESS) are rare tumors of the uterus. The metastasis
      of ESS to the cardiac structures is extremely infrequent. Several cases of right
      sided heart metastasis have been previously reported. To our knowledge, only one
      similar case is available in the published studies that presented with recurrent
      embolic strokes due to left atrial metastasis of ESS. In this report, we describe
      a 53-year-old woman with endometrial stromal sarcoma; she was referred to our
      hospital with subacute onset of severe dyspnea and a left atrial mass causing
      severe mitral stenosis.

PMID- 24658563
TI  - Jejunal diverticulitis: imaging to management.

PMID- 24658565
TI  - An unusual 2,3-secotaraxerene and other cytotoxic triterpenoids from Pleiocarpa
      pycnantha (Apocynaceae) leaves collected from Nigeria.
AB  - Three known triterpenoids, namely ursolic acid (1), and the 27-E- and 27-Z-p
      coumaric esters of ursolic acid (compounds 2, 3), were isolated together with a
      new triterpene 2,3-seco-taraxer-14-en-2,3-lactone [pycanocarpine (4)] from an
      ethanolic extract of Pleiocarpa pycnantha leaves. The structure of 4 was
      unambiguously assigned using NMR, HREIMS and X-ray crystallography. The cytotoxic
      activities of the compounds were evaluated against HeLa, MCF-7, KMST-6 and HT-29
      cells using the WST-1 assay. Ursolic acid (1) displayed potent cytotoxic activity
      against HeLa, HT-29 and MCF-7 cells with IC50 values of 10, 10 and 20 uM
      respectively. The new compound 4 and its hydrolysed derivative 5 were selectively
      cytotoxic to the breast cancer cell line, MCF-7 with IC50 values 20 and 10 uM
      respectively. This is the first report on isolation of a 2,3-seco-taraxerene
      derivative from the Apocynaceae family and cytotoxic activity of P. pycnantha
      constituents.

PMID- 24658566
TI  - Regioselective electrophilic aromatic bromination: theoretical analysis and
      experimental verification.
AB  - Electrophilic aromatic bromination is the most common synthetic method used to
      prepare aryl bromides, which are very useful intermediates in organic synthesis.
      To understand the experimental results in electrophilic aromatic brominations, ab
      initio calculations are used here for a tentative analysis of the positional
      selectivity. The calculated results agree well with the corresponding
      experimental data, and the reliability of the resulting positional selectivity
      was verified by the corresponding experimental data. 

PMID- 24658567
TI  - Synthesis, docking study and beta-adrenoceptor activity of some new oxime ether
      derivatives.
AB  - A new series of oxime ethers 4a-z was designed and synthesized to test the
      blocking activity against beta1 and beta2-adrenergic receptors. Docking of these
      ether derivatives into the active site of the identified 3D structures of beta1
      and beta2-adrenergic receptors showed MolDock scores comparable to those of
      reference compounds. Biological results revealed that the inhibition effects on
      the heart rate and contractility are less than those of propranolol.
      Nevertheless, the two compounds 4p and 4q that displayed the highest negative
      MolDock score with beta2-adrenergic receptors showed beta2-antagonistic activity
      by decreasing salbutamol relaxation of precontracted tracheal strips, which
      indicates the importance of a chlorothiophene moiety in the hydrophobic region
      for best complementarity with beta2 receptors. On other hand, the presence of a
      homoveratryl moiety increases the MolDock score of the tested compounds with the
      beta1 receptor.

PMID- 24658568
TI  - Synthesis of new 2,5-di-substituted 1,3,4-oxadiazoles bearing 2,6-di-tert
      butylphenol moieties and evaluation of their antioxidant activity.
AB  - Eleven new 2,6-di-tert-butyl-4-(5-aryl-1,3,4-oxadiazol-2-yl)phenols 5a-k were
      synthesized by reacting aryl hydrazides with 3,5-di-tert butyl 4-hydroxybenzoic
      acid in the presence of phosphorus oxychloride. The resulting compounds were
      characterized based on their IR, 1H-NMR, 13C-NMR, and HRMS data. 2,2-Diphenyl-1
      picrylhydrazide (DPPH) and ferric reducing antioxidant power (FRAP) assays were
      used to test the antioxidant properties of the compounds. Compounds 5f and 5j
      exhibited significant free-radical scavenging ability in both assays.

PMID- 24658569
TI  - Authentication of Bulbus Fritillariae Cirrhosae by RAPD-derived DNA markers.
AB  - Bulbus Fritillariae is the most commonly used antitussive herb in China. Eleven
      species of Fritillaria are recorded as Bulbus Fritillariae in the Chinese
      Pharmacopoeia. Bulbus Fritillariae Cirrhosae is a group of six Fritillaria
      species with higher efficiency and lower toxicity derived mainly from wild
      sources. Because of their higher market price, five other Fritillaria species are
      often sold deceptively as Bulbus Fritillariae Cirrhosae in the herbal market. To
      ensure the efficacy and safety of medicinal herbs, the authentication of
      botanical resources is the first step in quality control. Here, a DNA based
      identification method was developed to authenticate the commercial sources of
      Bulbus Fritillariae Cirrhosae. A putative DNA marker (0.65 kb) specific for
      Bulbus Fritillariae Cirrhosae was identified using the Random Amplified
      Polymorphic DNA (RAPD) technique. A DNA marker representing a Sequence
      Characterized Amplified Region (SCAR) was developed from a RAPD amplicon. The
      SCAR marker was successfully applied to differentiate Bulbus Fritillariae
      Cirrhosae from different species of Fritillaria. Additionally, the SCAR marker
      was also useful in identifying the commercial samples of Bulbus Fritillariae
      Cirrhosae. Our results indicated that the RAPD-SCAR method was rapid, accurate
      and applicable in identifying Bulbus Fritillariae Cirrhosae at the DNA level. 

PMID- 24658570
TI  - Metabonomic analysis of water extracts from different angelica roots by 1H
      nuclear magnetic resonance spectroscopy.
AB  - Angelica Radix, the roots of the genus Angelica, has been used for more than
      2,000 years as a traditional medicine in Eastern Asia. The Chinese Pharmacopoeia
      records more than 100 herbal formulae containing Angelica roots. There are two
      common sources of Angelica roots, Angelica sinensis from China and A. gigas from
      Korea. The two species of Angelica roots differ in their chemical compositions,
      pharmacological properties and clinical efficacy. 1H-NMR metabolic profiling has
      recently emerged as a promising quality control method for food and herbal
      chemistry. We explored the use of 1H-NMR metabolic profiling for the quality
      control of Angelica Radix. Unlike previous work, we performed the metabolic
      profiling on hot water extracts, so as to mimic the clinically relevant
      preparation method. Unsupervised principle component analyses of both the full
      spectral profile and a selection of targeted molecules revealed a clear
      differentiation of three types of Angelica roots. In addition, the levels of 13
      common metabolites were measured. Statistically significant differences in the
      levels of glucose, fructose and threonine were found between different sources of
      Angelica. Ferulic acid, a marker commonly used to evaluate Angelica root, was
      detected in our samples, but the difference in ferulic acid levels between the
      samples was not statistically significant. Overall, we successfully applied 1H
      NMR metabolic profiling with water extraction to discriminate all three sources
      of Angelica roots, and obtained quantitative information of many common
      metabolites.

PMID- 24658571
TI  - Inhibition of GlcNAc-processing glycosidases by C-6-azido-NAG-thiazoline and its
      derivatives.
AB  - NAG-thiazoline is a strong competitive inhibitor of GH20 beta-N-acetyl-
      hexosaminidases and GH84 beta-N-acetylglucosaminidases. Here, we focused on the
      design, synthesis and inhibition potency of a series of new derivatives of NAG
      thiazoline modified at the C-6 position. Dimerization of NAG-thiazoline via C-6
      attached triazole linkers prepared by click chemistry was employed to make use of
      multivalency in the inhibition. Novel compounds were tested as potential
      inhibitors of beta-N-acetylhexosaminidases from Talaromyces flavus, Streptomyces
      plicatus (both GH20) and beta-N-acetylglucosaminidases from Bacteroides
      thetaiotaomicron and humans (both GH84). From the set of newly prepared NAG
      thiazoline derivatives, only C-6-azido-NAG-thiazoline displayed inhibition
      activity towards these enzymes; C-6 triazole-substituted NAG-thiazolines lacked
      inhibition activity against the enzymes used. Docking of C-6-azido-NAG-thiazoline
      into the active site of the tested enzymes was performed. Moreover, a stability
      study with GlcNAc-thiazoline confirmed its decomposition at pH < 6 yielding 2
      acetamido-2-deoxy-1-thio-alpha/beta-D-glucopyranoses, which presumably dimerize
      oxidatively into S-S linked dimers; decomposition products of NAG-thiazoline are
      void of inhibitory activity. 

PMID- 24658572
TI  - Structural diversity of lamellar zeolite Nu-6(1)--postsynthesis of delaminated
      analogues.
AB  - Nu-6(1) zeolite, the lamellar precursor of NSI topology, was firstly synthesized
      with 4'4-bipyridine as the structure-directing agent (SDA) and then subjected to
      HCl-EtOH treatment for the purpose of structural modification. Interlayer
      deconstruction and reconstruction took place alternately in this acid treatment.
      An intermediate named ECNU-4 was separated at the initial stage of this
      continuous treatment process, which exhibited a special X-ray diffraction pattern
      without obvious reflection peaks at low angles. The zeolitic structure in the
      intralayer sheets was supposed to be well preserved in ECNU-4, whereas the
      interlayer structure became extremely disordered. The ECNU-4 intermediate showed
      structural diversity. It was converted into the reconstructed and interlayer
      expanded zeolite IEZ-NSI without an external silicon source by prolonging the HCl
      EtOH treatment to 24 h. Moreover, with a partially delaminated structure, ECNU-4
      was easily interlayer swollen at room temperature with cetyltrimethyl ammonium
      bromide in the presence of tetrapropyl ammonium hydroxide. The swollen material
      was further sonicated to yield a more deeply delaminated zeolite, Del-Nu-6. ECNU
      4 and Del-Nu-6 differed in delamination degree, structural disordering and
      textural properties, especially surface area. 

PMID- 24658573
TI  - Rational design of catalysts for asymmetric diamination reaction using transition
      state modeling.
AB  - The stereoselective synthesis of 1,2-diamines has remained a formidable
      challenge. A recent palladium-catalyzed asymmetric diamination of conjugated
      double bonds using di-tert-butyldiaziridinone appears promising. The axially
      chiral binol phosphoramidite ligands are successful in offering high
      enantioselectivity. The density functional theory investigations revealed that
      the energies of the stereocontrolling transition states for the C-N bond
      formation depend on a number of weak non-covalent interactions such as C-H...pi,
      C-H...O and anagostic interactions. We envisaged that the modulation in these
      interactions in the transition states, through subtle changes in chiral
      phosphoramidite substituents, could be exploited toward steering the
      stereoselectivity. The effect of systematic modifications on both 3,3' positions
      of the binol as well as on the amido nitrogen on the stereochemical outcome is
      predicted. It is identified that high enantioselectivity requires a balance
      between the nature of the substituents on binol and amido groups. The reduced
      size of the amido substituents demands increased bulk on the binol whereas
      lowering the size on the binol demands increased bulk on the amido for higher
      stereoselectivity. The substituent at the alpha-position of the amido group is
      found to be vital and appears to be a hot spot for modifications. These insights
      derived from studies on the stereocontrolling transition states could help
      improve the catalytic efficacies in palladium-catalyzed asymmetric diamination
      reactions.

PMID- 24658575
TI  - Label-free optical biosensor for detection and quantification of the non
      steroidal anti-inflammatory drug diclofenac in milk without any sample
      pretreatment.
AB  - A label-free optical biosensor for detection and quantification of diclofenac in
      bovine milk has been developed. This was achieved by using reflectometric
      interference spectroscopy as detection method. In a first step, the immunosensor
      was developed and optimised in buffer concerning sensitivity, selectivity,
      stability and reproducibility. By comparing recovery rates-not only the good
      intra- but also the good inter-chip-reproducibility could be proven.
      Consequently, the assay was transferred in the more complex matrix milk. By
      utilising an optimised surface modification and evaluation method, matrix effects
      could successfully be prevented or circumvented. As a result, the developed
      immunosensor does not need sample pretreatment at all. By obtaining a limit of
      detection of 0.112 MUg L(-1) (0.108 MUg kg(-1)), the capability of the developed
      biosensor is comparable or better than those of standard detection methods.
      Moreover, the presented biosensor reaches the range of the maximum residue limit
      (0.1 MUg kg(-1)) set by the European Union. Thus, for the first time, diclofenac
      was successfully quantified at relevant levels in milk by using an optical
      biosensor.

PMID- 24658574
TI  - Identification of microRNAs in the coral Stylophora pistillata.
AB  - Coral reefs are major contributors to marine biodiversity. However, they are in
      rapid decline due to global environmental changes such as rising sea surface
      temperatures, ocean acidification, and pollution. Genomic and transcriptomic
      analyses have broadened our understanding of coral biology, but a study of the
      microRNA (miRNA) repertoire of corals is missing. miRNAs constitute a class of
      small non-coding RNAs of ~22 nt in size that play crucial roles in development,
      metabolism, and stress response in plants and animals alike. In this study, we
      examined the coral Stylophora pistillata for the presence of miRNAs and the
      corresponding core protein machinery required for their processing and function.
      Based on small RNA sequencing, we present evidence for 31 bona fide microRNAs, 5
      of which (miR-100, miR-2022, miR-2023, miR-2030, and miR-2036) are conserved in
      other metazoans. Homologues of Argonaute, Piwi, Dicer, Drosha, Pasha, and HEN1
      were identified in the transcriptome of S. pistillata based on strong sequence
      conservation with known RNAi proteins, with additional support derived from
      phylogenetic trees. Examination of putative miRNA gene targets indicates
      potential roles in development, metabolism, immunity, and biomineralisation for
      several of the microRNAs. Here, we present first evidence of a functional RNAi
      machinery and five conserved miRNAs in S. pistillata, implying that miRNAs play a
      role in organismal biology of scleractinian corals. Analysis of predicted miRNA
      target genes in S. pistillata suggests potential roles of miRNAs in symbiosis and
      coral calcification. Given the importance of miRNAs in regulating gene expression
      in other metazoans, further expression analyses of small non-coding RNAs in
      transcriptional studies of corals should be informative about miRNA-affected
      processes and pathways. 

PMID- 24658576
TI  - Receptor interacting protein-2 plays a critical role in human lung epithelial
      cells survival in response to Fas-induced cell-death.
AB  - Lung epithelial cell death is critical to the lung injury that occurs in the
      acute respiratory distress syndrome. It is known that FasL plays a prominent role
      in this lung cell death pathway and may work in part through activation of the
      receptor interacting protein-2 (RIP2). RIP2 is serine/threonine kinase with a C
      terminal caspase activation and recruitment domain (CARD). This CARD contains a
      highly conserved, predicted tyrosine phosphorylation site. Thus, involvement of
      tyrosine phosphorylation in the CARD domain of RIP2 may play a critical role in
      Fas-mediated apoptosis in the human lung immune system. To test this hypothesis,
      human lung epithelial cells (BEAS-2B) were induced to undergo cell death in
      response to the Fas agonist antibody CH11 with and without manipulation of
      endogenous RIP2 concentrations. We show that CH11 increases lung epithelial cell
      death in a dose-dependent manner as determined by LDH release and nuclear
      condensation. Fas-induced LDH release was inhibited by RIP2 knock-down. Reduced
      levels of RIP2 in BEAS-2B cells after treatment with RIP2 siRNA were confirmed by
      immunoblot. Overexpression of RIP2 in BEAS-2B cells synergized with Fas ligand
      induced LDH release in a dose-dependent manner. Finally, mutation of the tyrosine
      phosphorylation site in CARD of RIP2 protected BEAS-2B cells from Fas ligand
      induced cell death. Thus RIP2's CARD tyrosine phosphorylation may represent a new
      therapeutic target to promote the survival of human lung epithelial cells in
      disorders that lead to acute lung injury and ARDS. 

PMID- 24658577
TI  - Inhibition of calcineurin abrogates while inhibition of mTOR promotes regulatory
      T cell expansion and graft-versus-host disease protection by IL-2 in allogeneic
      bone marrow transplantation.
AB  - Regulatory T cells (Treg)s attenuate excessive immune responses, making their
      expansion beneficial in immune-mediated diseases including allogeneic bone marrow
      transplantation (BMT)-associated graft-versus-host disease (GVHD). We have
      recently reported that Treg expansion does not require phospholipase Cgamma
      activation when IL-2 is provided. As such, the combination of IL-2 and a
      calcineurin inhibitor (Cyclosporine A; CsA) expands Tregs while inhibiting Tconv
      proliferation and protects against a mouse model of multiple sclerosis. However,
      CsA inhibits Treg proliferation in the presence of a TCR stimulus, suggesting
      that CsA may negatively impact Treg proliferation when they receive strong
      allogeneic MHC-mediated TCR signals. In this study, we show that CsA inhibits
      Treg proliferation and inducible Treg generation in allogeneic but not in
      syngeneic BMT when IL-2 is provided. In contrast to CsA, the mTOR inhibitor
      (Rapamycin) almost completely suppressed IL-2-mediated Treg proliferation.
      However, CsA and Rapamycin inhibited Treg proliferation to a similar extent when
      TCR stimulation was provided. Furthermore, Rapamycin promoted Treg expansion and
      inducible Treg generation in allogeneic BMT recipients treated with IL-2.
      Consistent with these observations, CsA abrogated while Rapamycin promoted the
      protective effect of IL-2 on allogeneic BMT-induced GVHD. These results suggest
      that while CsA permits IL-2-induced Treg proliferation in the syngeneic setting
      (absence of strong TCR signals), CsA in combination with IL-2 may be detrimental
      for Treg proliferation in an allogeneic setting. Thus, in allogeneic settings, an
      mTOR inhibitor such as Rapamycin is a better choice for adjunct therapy with IL-2
      in expansion of Tregs and protection against allogeneic BMT-induced GVHD. 

PMID- 24658578
TI  - Semi-automatic classification of birdsong elements using a linear support vector
      machine.
AB  - Birdsong provides a unique model for understanding the behavioral and neural
      bases underlying complex sequential behaviors. However, birdsong analyses require
      laborious effort to make the data quantitatively analyzable. The previous
      attempts had succeeded to provide some reduction of human efforts involved in
      birdsong segment classification. The present study was aimed to further reduce
      human efforts while increasing classification performance. In the current
      proposal, a linear-kernel support vector machine was employed to minimize the
      amount of human-generated label samples for reliable element classification in
      birdsong, and to enable the classifier to handle highly-dimensional acoustic
      features while avoiding the over-fitting problem. Bengalese finch's songs in
      which distinct elements (i.e., syllables) were aligned in a complex sequential
      pattern were used as a representative test case in the neuroscientific research
      field. Three evaluations were performed to test (1) algorithm validity and
      accuracy with exploring appropriate classifier settings, (2) capability to
      provide accuracy with reducing amount of instruction dataset, and (3) capability
      in classifying large dataset with minimized manual labeling. The results from the
      evaluation (1) showed that the algorithm is 99.5% reliable in song syllables
      classification. This accuracy was indeed maintained in evaluation (2), even when
      the instruction data classified by human were reduced to one-minute excerpt
      (corresponding to 300-400 syllables) for classifying two-minute excerpt. The
      reliability remained comparable, 98.7% accuracy, when a large target dataset of
      whole day recordings (~30,000 syllables) was used. Use of a linear-kernel support
      vector machine showed sufficient accuracies with minimized manually generated
      instruction data in bird song element classification. The methodology proposed
      would help reducing laborious processes in birdsong analysis without sacrificing
      reliability, and therefore can help accelerating behavior and studies using
      songbirds. 

PMID- 24658579
TI  - Malaria protein kinase CK2 (PfCK2) shows novel mechanisms of regulation.
AB  - Casein kinase 2 (protein kinase CK2) is a conserved eukaryotic serine/theronine
      kinase with multiple substrates and roles in the regulation of cellular processes
      such as cellular stress, cell proliferation and apoptosis. Here we report a
      detailed analysis of the Plasmodium falciparum CK2, PfCK2, demonstrating that
      this kinase, like the mammalian orthologue, is a dual specificity kinase able to
      phosphorylate at both serine and tyrosine. However, unlike the human orthologue
      that is auto-phosphorylated on tyrosine within the activation loop, PfCK2 shows
      no activation loop auto-phosphorylation but rather is auto-phosphorylated at
      threonine 63 within subdomain I. Phosphorylation at this site in PfCK2 is shown
      here to regulate the intrinsic kinase activity of PfCK2. Furthermore, we generate
      an homology model of PfCK2 in complex with the known selective protein kinase CK2
      inhibitor, quinalizarin, and in so doing identify key co-ordinating residues in
      the ATP binding pocket that could aid in designing selective inhibitors to PfCK2.

PMID- 24658580
TI  - Biased imitation in coupled evolutionary games in interdependent networks.
AB  - We explore the evolutionary dynamics of two games-the Prisoner's Dilemma and the
      Snowdrift Game-played within distinct networks (layers) of interdependent
      networks. In these networks imitation and interaction between individuals of
      opposite layers is established through interlinks. We explore an update rule in
      which revision of strategies is a biased imitation process: individuals imitate
      neighbors from the same layer with probability p, and neighbors from the second
      layer with complementary probability 1 - p. We demonstrate that a small decrease
      of p from p = 1 (which corresponds to forbidding strategy transfer between
      layers) is sufficient to promote cooperation in the Prisoner's Dilemma
      subpopulation. This, on the other hand, is detrimental for cooperation in the
      Snowdrift Game subpopulation. We provide results of extensive computer
      simulations for the case in which layers are modelled as regular random networks,
      and support this study with analytical results for coupled well-mixed
      populations. 

PMID- 24658582
TI  - Prediction of conductivity by adaptive neuro-fuzzy model.
AB  - Electrochemical impedance spectroscopy (EIS) is a key method for the
      characterizing the ionic and electronic conductivity of materials. One of the
      requirements of this technique is a model to forecast conductivity in preliminary
      experiments. The aim of this paper is to examine the prediction of conductivity
      by neuro-fuzzy inference with basic experimental factors such as temperature,
      frequency, thickness of the film and weight percentage of salt. In order to
      provide the optimal sets of fuzzy logic rule bases, the grid partition fuzzy
      inference method was applied. The validation of the model was tested by four
      random data sets. To evaluate the validity of the model, eleven statistical
      features were examined. Statistical analysis of the results clearly shows that
      modeling with an adaptive neuro-fuzzy is powerful enough for the prediction of
      conductivity. 

PMID- 24658581
TI  - Human beta-defensin-1 suppresses tumor migration and invasion and is an
      independent predictor for survival of oral squamous cell carcinoma patients.
AB  - BACKGROUND: Human beta-defensin-1 (hBD-1) has recently been considered as a
      candidate tumor suppressor in renal and prostate cancer. The aim of this study
      was to investigate the role of hBD-1 in the progression of oral squamous cell
      carcinoma (OSCC) and its potential as diagnostic/prognostic biomarker and
      therapeutic target for OSCC. METHODS: HBD-1 expression in tissues at different
      stages of oral carcinogenesis, as well as OSCC cell lines was examined. HBD-1 was
      overexpressed in HSC-3, UM1, SCC-9 and SCC-25 cells and subjected to cell growth,
      apoptosis, migration and invasion assays. Tissue microarray constructed with
      tissues from 175 patients was used to examine clinicopathological significance of
      hBD-1 expression in OSCC. RESULTS: HBD-1 expression decreased from oral
      precancerous lesions to OSCC and was lower in OSCC with lymph node metastasis
      than those without metastasis. In vitro, the expression of hBD-1 was related to
      the invasive potential of OSCC cell lines. Induction of exogenous expression of
      hBD-1 inhibited migration and invasion of OSCC cells, probably by regulation of
      RhoA, RhoC and MMP-2; but had no significant effect on proliferation or
      apoptosis. In a cohort of patients with primary OSCC, cases with no expression of
      hBD-1 had more chance to be involved in lymph node metastasis. Eventually, the
      positive expression of hBD-1 was associated with longer survival of patients with
      OSCC, and multivariate analysis and ROC curve analysis confirmed hBD-1 positivity
      to be an independent prognostic factor of OSCC, especially OSCC at early stage.
      CONCLUSIONS: Overall, these data indicated that hBD-1 suppressed tumor migration
      and invasion of OSCC and was likely to be a prognostic biomarker and a potential
      target for treatment of OSCC.

PMID- 24658583
TI  - Overexpression of lymphoid enhancer-binding factor 1 (LEF1) in solid
      pseudopapillary neoplasms of the pancreas.
AB  - Solid-pseudopapillary neoplasms are rare, but are distinctive pancreatic tumors
      of low-malignant potential. While the histogenesis of these tumors is unclear,
      they are often associated with gain-of-function mutations in the catenin
      (cadherin-associated protein), beta 1 (88 kDa), or CTNNB1 gene, resulting in
      nuclear accumulation of CTNNB1. CTNNB1 is a central component of the Wnt
      signaling pathway and mediates gene expression through the lymphoid enhancer
      binding factor 1 (LEF1) /T-cell factor transcription complex. Although LEF1 has a
      pivotal role in the transactivation of Wnt/CTNNB1 responsive genes, the status of
      LEF1 in solid-pseudopapillary neoplasms and other pancreatic tumors has not been
      examined. We analyzed both LEF1 and CTNNB1 in a large cohort of pancreatic tumors
      (n=155). In all cases of solid-pseudopapillary neoplasms including surgical
      resections (n=27) and cytologic samples (n=8) had strong and diffuse nuclear
      labeling for both LEF1 and CTNNB1. The surrounding uninvolved pancreatic
      parenchyma was devoid of any LEF1 staining. All resection and cytologic specimens
      from well-differentiated pancreatic neuroendocrine tumors (n=44; n=29,
      respectively), high-grade pancreatic neuroendocrine carcinomas (n=2; n=1),
      pancreatic ductal adenocarcinomas (n=25; n=12), and acinar cell carcinomas (n=9;
      n=2) studied were negative for both nuclear LEF1 and CTNNB1. However, nuclear
      LEF1 and CTNNB1 were detected in all four resected pancreatoblastomas (no
      cytologic specimens were available for immunolabeling), but primarily centered
      around and within squamoid corpuscles. In summary, abnormal CTNNB1 accumulation
      was accompanied by nuclear LEF1 overexpression in both solid-pseudopapillary
      neoplasms and pancreatoblastomas. But, in contrast to pancreatoblastomas, a
      diffuse, nuclear labeling was observed in solid-pseudopapillary neoplasms and
      further implicates the CTNNB1/LEF1 transcriptional complex in the development of
      solid-pseudopapillary neoplasms. In addition, as part of an immunohistochemical
      panel, LEF1 can be a useful ancillary stain in the diagnosis of solid
      pseudopapillary neoplasms. 

PMID- 24658586
TI  - Generation of a large volume of clinically relevant nanometre-sized ultra-high
      molecular-weight polyethylene wear particles for cell culture studies.
AB  - It has recently been shown that the wear of ultra-high-molecular-weight
      polyethylene in hip and knee prostheses leads to the generation of nanometre
      sized particles, in addition to micron-sized particles. The biological activity
      of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has
      not, however, previously been studied due to difficulties in generating
      sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene
      wear particles suitable for cell culture studies. In this study, wear simulation
      methods were investigated to generate a large volume of endotoxin-free clinically
      relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles.
      Both single-station and six-station multidirectional pin-on-plate wear simulators
      were used to generate ultra-high-molecular-weight polyethylene wear particles
      under sterile and non-sterile conditions. Microbial contamination and endotoxin
      levels in the lubricants were determined. The results indicated that microbial
      contamination was absent and endotoxin levels were low and within acceptable
      limits for the pharmaceutical industry, when a six-station pin-on-plate wear
      simulator was used to generate ultra-high-molecular-weight polyethylene wear
      particles in a non-sterile environment. Different pore-sized polycarbonate
      filters were investigated to isolate nanometre-sized ultra-high-molecular-weight
      polyethylene wear particles from the wear test lubricants. The use of the filter
      sequence of 10, 1, 0.1, 0.1 and 0.015 um pore sizes allowed successful isolation
      of ultra-high-molecular-weight polyethylene wear particles with a size range of <
      100 nm, which was suitable for cell culture studies.

PMID- 24658585
TI  - COMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy
      and Working Memory in Mice and Humans.
AB  - Genetic variations in catechol-O-methyltransferase (COMT) that modulate cortical
      dopamine have been associated with pleiotropic behavioral effects in humans and
      mice. Recent data suggest that some of these effects may vary among sexes.
      However, the specific brain substrates underlying COMT sexual dimorphisms remain
      unknown. Here, we report that genetically driven reduction in COMT enzyme
      activity increased cortical thickness in the prefrontal cortex (PFC) and postero
      parieto-temporal cortex of male, but not female adult mice and humans.
      Dichotomous changes in PFC cytoarchitecture were also observed: reduced COMT
      increased a measure of neuronal density in males, while reducing it in female
      mice. Consistent with the neuroanatomical findings, COMT-dependent sex-specific
      morphological brain changes were paralleled by divergent effects on PFC-dependent
      working memory in both mice and humans. These findings emphasize a specific sex
      gene interaction that can modulate brain morphological substrates with influence
      on behavioral outcomes in healthy subjects and, potentially, in neuropsychiatric
      populations. 

PMID- 24658584
TI  - The CD1 size problem: lipid antigens, ligands, and scaffolds.
AB  - Whereas research on CD1d has emphasized a few glycosyl ceramides, the broader
      family of four human CD1 antigen-presenting molecules binds hundreds of distinct
      self-lipids. Individual lipid types bind within CD1 grooves in different ways,
      such that they partially fill the groove, match the groove volume, or protrude
      substantially from the groove. These differing modes of binding can now be
      connected to differing immunological functions, as individual lipids can act as
      stimulatory antigens, inhibitory ligands, or space-filling scaffolds. Because
      each type of CD1 protein folds to produce antigen-binding grooves with differing
      sizes and shapes, CD1a, CD1b, CD1c, CD1d, and CD1e have distinct mechanisms of
      capturing self-lipids and exchanging them for foreign lipids. The size
      discrepancy between endogeneous lipids and groove volume is most pronounced for
      CD1b. Recent studies show that the large CD1b cavity can simultaneously bind two
      self-lipids, the antigen, and its scaffold lipid, which can be exchanged for one
      large bacterial lipid. In this review, we will highlight recent studies showing
      how cells regulate lipid antigen loading and the roles CD1 groove structures have
      in control of the presentation of chemically diverse lipids to T cells.

PMID- 24658587
TI  - A new "functional" pasta containing tartary buckwheat sprouts as an ingredient
      improves the oxidative status and normalizes some blood pressure parameters in
      spontaneously hypertensive rats.
AB  - Epidemiological studies have reported that some foods, particularly those rich in
      (poly)phenols, may reduce cardiovascular risk and metabolic disorders such as
      hypertension. Buckwheat sprouts have been suggested as a new raw material for the
      production of functional foods due to their high content of healthy compounds
      such as rutin and quercetin. The aim of this paper is to evaluate the biological
      hypotensive and antioxidant responses of pasta containing tartary buckwheat
      sprouts (TBSP) on spontaneously hypertensive rats (SHR). In this study, dry
      tartary buckwheat sprouts were milled to obtain a powder that was used in the
      production of pasta containing 30% dry buckwheat sprouts and 70% durum wheat
      semolina. Afterwards, we analyzed the in vitro TBSP features compared with the
      control (durum wheat flour pasta, DWFP), and the in vivo effects of TBSP on SHR
      and their normotensive counterpart, Wistar Kyoto rats (WKY rats). The total
      phenolic content and antioxidant activity were higher in TBSP compared to DWFP.
      The results showed that SHR fed TBSP exhibited higher plasma levels of the
      endogenous vasodilators bradykinin (BK) and nitric oxide (NO), a lower level of
      the vasoconstrictor endothelin-1 (ET-1), and an improved antioxidant capacity.
      These data suggest that TBSP may help reduce hypertension and oxidative stress in
      vivo. 

PMID- 24658589
TI  - Quantitative evaluation of the thermal heterogeneity on the surface of
      cryotherapy cooling pads.
AB  - We have investigated thermal operating characteristics of 13 commercially
      available cryotherapy units (CTUs) and their associated cooling pads using IR
      imaging. Quantitative examination of the temperature profiles from pad IR images
      shows diverse, nonuniform temperature distribution patterns. The extent of
      heterogeneity of the temperature fields was quantified via standard image
      analysis methods, including thresholding, spatial gradient diagrams, and
      frequency histogram distributions. A primary conclusion of this study is that it
      is a misnomer to characterize the thermal performance of a CTU and cooling pad
      combination in terms of a single therapeutic temperature.

PMID- 24658588
TI  - Dietary zinc deficiency affects blood linoleic acid: dihomo-gamma-linolenic acid
      (LA:DGLA) ratio; a sensitive physiological marker of zinc status in vivo (Gallus
      gallus).
AB  - Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple
      biochemical and structural processes in the body. To date, sensitive and specific
      biological markers of zinc status are still needed. The aim of this study was to
      evaluate Gallus gallus as an in vivo model in the context of assessing the
      sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte
      linoleic acid: dihomo-gamma-linolenic acid (LA:DGLA) ratio. Diets identical in
      composition were formulated and two groups of birds (n = 12) were randomly
      separated upon hatching into two diets, Zn+ (zinc adequate control, 42.3 MUg/g
      zinc), and Zn- (zinc deficient, 2.5 MUg/g zinc). Dietary zinc intake, body
      weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly.
      At the conclusion of the study, tissues were collected for gene expression
      analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher
      in the Zn+ control versus Zn- group (p < 0.05). Hepatic TNF-alpha, IL-1beta, and
      IL-6 gene expression were higher in the Zn+ control group (p < 0.05), and hepatic
      Delta6 desaturase was significantly higher in the Zn+ group (p < 0.001). The
      LA:DGLA ratio was significantly elevated in the Zn- group compared to the Zn+
      group (22.6 +/- 0.5 and 18.5 +/- 0.5, % w/w, respectively, p < 0.001). This study
      suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc
      adequate and zinc deficient birds, and may be a sensitive biomarker to assess
      dietary zinc manipulation.

PMID- 24658590
TI  - Enhanced stability of alcohol dehydrogenase by non-covalent interaction with
      polysaccharides.
AB  - Non-covalent interaction of alcohol dehydrogenase with polysaccharides was
      studied using three neutral and three anionic polysaccharides. The process of
      interaction of alcohol dehydrogenase with gum Arabic was optimized with respect
      to the ratio of enzyme to gum Arabic, pH, and molarity of buffer. Alcohol
      dehydrogenase-gum Arabic complex formed under optimized conditions showed 93%
      retention of original activity with enhanced thermal and pH stability. Lower
      inactivation rate constant of alcohol dehydrogenase-gum Arabic complex within the
      temperature range of 45 to 60  degrees C implied its better stability. Half-life
      of alcohol dehydrogenase-gum Arabic complex was higher than that of free alcohol
      dehydrogenase. A slight increment was observed in kinetic constants (K(m) and
      V(max)) of gum Arabic-complexed alcohol dehydrogenase which may be due to
      interference by gum Arabic for the binding of substrate to the enzyme. Helix to
      turn conversion was observed in complexed alcohol dehydrogenase as compared to
      free alcohol dehydrogenase which may be responsible for observed stability
      enhancement.

PMID- 24658591
TI  - Efficient synthesis of (R)-3-hydroxypentanenitrile in high enantiomeric excess by
      enzymatic reduction of 3-oxopentanenitrile.
AB  - (R)-3-Hydroxypentanenitrile (HPN) is an important intermediate in the synthesis
      of an immunosuppressive inosine 5'-monophosphate dehydrogenase inhibitor. An
      efficient enzymatic procedure for the synthesis of (R)-HPN with over 99 %
      enantiomeric excess using a novel acetoacetyl-CoA reductase (AdKR) from
      Achromobacter denitrificans was successfully established. Many microorganisms are
      known to reduce 3-oxopentannitrile (KPN) to (R)-HPN. An enzyme from A.
      denitrificans partially purified using ion exchange chromatography reduced KPN to
      (R)-HPN with high enantioselectivity. The AdKR gene was cloned and sequenced and
      found to comprise 738 bp and encode a polypeptide of 26,399 Da. The deduced amino
      acid sequence showed a high degree of similarity to those of other putative
      acetoacetyl-CoA reductases and putative 3-ketoacyl-ACP reductases. The AdKR gene
      was singly expressed and coexpressed together with a glucose dehydrogenase (GDH)
      as a coenzyme regenerator in Escherichia coli under the control of the lac
      promoter. (R)-HPN was synthesized with over 99 % e.e. using a cell-free extract
      of recombinant E. coli cells coexpressing AdKR and GDH.

PMID- 24658592
TI  - Multiphase coexistence and destabilization of liquid crystalline binary nanosheet
      colloids of titanate and clay.
AB  - A plate-plate binary colloid system of photocatalytically active titanate and
      inert clay nanosheets shows macroscopically separated multiphase coexistence. Two
      liquid crystalline phases and one isotropic phase coexist at high titanate and
      low clay concentrations whereas the colloids are destabilized at high clay
      concentrations. 

PMID- 24658593
TI  - Prediction of RNA binding residues: an extensive analysis based on structure and
      function to select the best predictor.
AB  - Protein-RNA complexes play key roles in several cellular processes by the
      interactions of amino acids with RNA. To understand the recognition mechanism, it
      is important to identify the specific amino acids involved in RNA binding.
      Various computational methods have been developed for predicting RNA binding
      residues from protein sequence. However, their performances mainly depend on the
      training dataset, feature selection for developing a model and learning capacity
      of the model. Hence, it is important to reveal the correspondence between the
      performance of methods and properties of RNA-binding proteins (RBPs). In this
      work, we have collected all available RNA binding residues prediction methods and
      revealed their performances on unbiased, stringent and diverse datasets for RBPs
      with less than 25% sequence identity based on structural class, fold,
      superfamily, family, protein function, RNA type, RNA strand and RNA conformation.
      The best methods for each type of RBPs and the type of RBPs, which require
      further refinement in prediction, have been brought out. We also analyzed the
      performance of these methods for the disordered regions, structures which are not
      included in the training dataset and recently solved structures. The reliability
      of prediction is better than randomly choosing any method or combination of
      methods. This approach would be a valuable resource for biologists to choose the
      best method based on the type of RBPs for designing their experiments and the
      tool is freely accessible online at www.iitm.ac.in/bioinfo/RNA-protein/. 

PMID- 24658594
TI  - Protein intake and kidney function in the middle-age population: contrast between
      cross-sectional and longitudinal data.
AB  - BACKGROUND: Protein intake is considered a determinant of glomerular filtration
      rate (GFR). Urinary urea is an objective marker of protein intake. The population
      based study investigated, cross-sectionally and longitudinally, the association
      of protein intake with GFR, indexed by estimated GFR (eGFR). METHODS: Data were
      collected on overnight urinary urea, serum creatinine (S-cr), eGFR and other
      variables in 1522 men and women aged 45-64 years who participated in the Gubbio
      study (baseline). S-Cr, eGFR and other variables were re-assessed in 1144 of the
      1425 survivors after 12-year follow-up. RESULTS: At baseline, mean +/- SD was
      84.0 +/- 11.4 mL/min * 1.73 m(2) for eGFR calculated by CKD-Epi equation and 1.34
      +/- 0.57 g/day per kg of ideal weight for protein intake assessed by measurements
      of overnight urine excretion of urea nitrogen. Cross-sectional analyses of
      baseline data indicated a positive correlation of protein intake with eGFR (R =
      0.180, P < 0.001). In multi-variable regression, 1 g/day higher protein intake
      related to 4.7 mL/min * 1.73 m(2) higher eGFR [95% confidence interval (CI) =
      3.7/5.7]. At follow-up, mean +/- SD of 12-year eGFR change was -11.6 +/- 9.0
      mL/min * 1.73 m(2). Baseline protein intake correlated with more negative eGFR
      change (R = -0.251, P < 0.001). In multi-variable regression, 1 g/day higher
      protein intake related to -4.1 mL/min * 1.73 m(2) more negative eGFR change (95%
      CI = -5.1/-3.1) and to 1.78 risk for incidence of eGFR < 60 mL/min * 1.73 m(2)
      (95% CI = 1.15/2.78). CONCLUSIONS: In middle-aged adults, high protein intake is
      associated cross-sectionally with higher GFR but longitudinally with greater GFR
      decline over time.

PMID- 24658595
TI  - Role of aberrant PI3K pathway activation in gallbladder  tumorigenesis.
AB  - The PI3K/AKT pathway governs a plethora of cellular processes, including cell
      growth, proliferation, and metabolism, in response to growth factors and
      cytokines. By acting as a unique lipid phosphatase converting
      phosphatidylinositol-3,4,5,- trisphosphate (PIP3) to phosphatidylinositol-4,5,
      bisphosphate (PIP2), phosphatase and tensin homolog (PTEN) acts as the major
      cellular suppressor of PI3K signaling and AKT activation. Recently, PI3K
      mutations and loss/mutation of PTEN have been characterized in human gallbladder
      tumors; whether aberrant PTEN/PI3K pathway plays a causal role in gallbladder
      carcinogenesis, however, remains unknown. Herein we show that in mice,
      deregulation of PI3K/AKT signaling is sufficient to transform gallbladder
      epithelial cells and trigger fully penetrant, highly proliferative gallbladder
      tumors characterized by high levels of phospho-AKT. Histopathologically, these
      mouse tumors faithfully resemble human adenomatous gallbladder lesions. The
      identification of PI3K pathway deregulation as both an early event in the
      neoplastic transformation of the gallbladder epithelium and a main mechanism of
      tumor growth in Pten heterozygous and Pten mutant mouse models provides a new
      framework for studying in vivo the efficacy of target therapies directed against
      the PI3K pathway, as advanced metastatic tumors are often addicted to "trunkular"
      mutations.

PMID- 24658596
TI  - High acidity unilamellar zeolite MCM-56 and its pillared and delaminated
      derivatives.
AB  - The unilamellar form of zeolite MWW, MCM-56, which is obtained by direct
      hydrothermal synthesis has been studied with regard to acidity and porosity in
      its original and post-synthesis modified pillared and delaminated forms. The
      acidity measured by FTIR was found to be only slightly lower than the highly
      active 3-D MWW forms, MCM-22 and MCM-49. Pivalonitrile adsorption, which is a
      measure of spatial openness, showed 50% accessibility vs. <30% for MCM-22/49. It
      highlights the potential of MCM-56 as a layered material with increased access to
      acid sites because it does not entail laborious post-synthesis modification.
      Swelling, pillaring and delamination of MCM-56 are facile but result in a
      reduction in the number of Bronsted acid sites (BAS) while increasing
      accessibility to pivalonitrile. The delamination procedure involving sonication
      and acidification of the highly basic mother liquor produces the most visible
      increase in surface area and access to all BAS. The accompanying doubling of the
      solid yield and the decrease in absolute number of BAS suggest significant
      precipitation of dissolved silica generated during swelling and sonication in
      high pH medium. The viability of separating surfactant covered layers upon
      sonication with the consequence of exposing hydrophobic hydrocarbon tails to
      aqueous environment is addressed. 

PMID- 24658598
TI  - Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces
      recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled
      study.
AB  - BACKGROUND: Patients with high Rockall scores have increased risk of ulcer
      rebleeding after 3-day esomeprazole infusions. OBJECTIVE: To investigate whether
      double oral esomeprazole given after a 3-day esomeprazole infusion decreases
      ulcer rebleeding for patients with high Rockall scores. DESIGN: We prospectively
      enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic
      haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores
      >=6 were randomised into the oral double-dose group (n=93) or the oral standard
      dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or
      once daily, respectively. The patients with Rockall scores <6 served as controls
      (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter,
      all patients received oral esomeprazole 40 mg once daily for two more weeks until
      the end of the 28-day study period. The primary end point was peptic ulcer
      rebleeding. RESULTS: Among patients with Rockall scores >=6, the oral double-dose
      group had a higher cumulative rebleeding-free proportion than the oral standard
      dose group (p=0.02, log-rank test). The proportion of patients free from
      recurrent bleeding during the 4th-28th day in the oral double-dose group remained
      lower than that of the group with Rockall scores <6 (p=0.03, log-rank test).
      Among patients with Rockall scores >=6, the rebleeding rate was lower in the oral
      double-dose group than in the oral standard-dose group (4th-28th day: 10.8% vs
      28.7%, p=0.002). CONCLUSIONS: Double oral esomeprazole at 40 mg twice daily after
      esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk
      patients with Rockall scores >=6. TRIAL REGISTRATION NUMBER: NCT01591083.

PMID- 24658599
TI  - Bacterial genotoxin colibactin promotes colon tumour growth by inducing a
      senescence-associated secretory phenotype.
AB  - BACKGROUND: Escherichia coli strains harbouring the pks island (pks+ E. coli) are
      often seen in human colorectal tumours and have a carcinogenic effect independent
      of inflammation in an AOM/IL-10(-/-) (azoxymethane/interleukin) mouse model.
      OBJECTIVE: To investigate the mechanism sustaining pks+ E. coli-induced
      carcinogenesis. METHOD: Underlying cell processes were investigated in vitro and
      in vivo (xenograft model) using intestinal epithelial cells infected by pks+ E.
      coli or by an isogenic mutant defective for pks (pks- E. coli). The results were
      supported by data obtained from an AOM/DSS (azoxymethane/dextran sodium sulphate)
      colon cancer mouse model and from human colon cancer biopsy specimens colonised
      by pks+ E. coli or pks- E. coli. RESULTS: Colibactin-producing E. coli enhanced
      tumour growth in both xenograft and AOM/DSS models. Growth was sustained by
      cellular senescence (a direct consequence of small ubiquitin-like modifier (SUMO)
      conjugated p53 accumulation), which was accompanied by the production of
      hepatocyte growth factor (HGF). The underlying mechanisms involve microRNA-20a
      5p, which targets SENP1, a key protein regulating p53 deSUMOylation. These
      results are consistent with the expression of SENP1, microRNA-20a-5p, HGF and
      phosphorylation of HGF receptor found in human and mouse colon cancers colonised
      by pks+ E. coli. CONCLUSION: These data reveal a new paradigm for carcinogenesis,
      in which colibactin-induced senescence has an important role.

PMID- 24658600
TI  - Motion-induced blindness and Troxler fading: common and different mechanisms.
AB  - Extended stabilization of gaze leads to disappearance of dim visual targets
      presented peripherally. This phenomenon, known as Troxler fading, is thought to
      result from neuronal adaptation. Intense targets also disappear intermittently
      when surrounded by a moving pattern (the "mask"), a phenomenon known as motion
      induced blindness (MIB). The similar phenomenology and dynamics of these
      disappearances may suggest that also MIB is, likewise, solely due to adaptation,
      which may be amplified by the presence of the mask. Here we directly compared the
      dependence of both phenomena on target contrast. Observers reported the
      disappearance and reappearance of a target of varying intensity (contrast levels:
      8%-80%). MIB was induced by adding a mask that moved at one of various different
      speeds. The results revealed a lawful effect of contrast in both MIB and Troxler
      fading, but with opposite trends. Increasing target contrast increased (doubled)
      the rate of disappearance events for MIB, but decreased the disappearance rate to
      half in Troxler fading. The target mean invisible period decreased equally
      strongly with target contrast in MIB and in Troxler fading. The results suggest
      that both MIB and Troxler are equally affected by contrast adaptation, but that
      the rate of MIB is governed by an additional mechanism, possibly involving
      antagonistic processes between neuronal populations processing target and mask.
      Our results link MIB to other bi-stable visual phenomena that involve neuronal
      competition (such as binocular rivalry), which exhibit an analogous dependency on
      the strength of the competing stimulus components. 

PMID- 24658601
TI  - Development and validation of the pediatric AzBio sentence lists.
AB  - OBJECTIVES: The goal of this study was to create and validate a new set of
      sentence lists that could be used to evaluate the speech-perception abilities of
      listeners with hearing loss in cases where adult materials are inappropriate due
      to difficulty level or content. The authors aimed to generate a large number of
      sentence lists with an equivalent level of difficulty for the evaluation of
      performance over time and across conditions. DESIGN: The original Pediatric AzBio
      sentence corpus included 450 sentences recorded from one female talker. All
      sentences included in the corpus were successfully repeated by kindergarten and
      first-grade students with normal hearing. The mean intelligibility of each
      sentence was estimated by processing each sentence through a cochlear implant
      simulation and calculating the mean percent correct score achieved by 15 normal
      hearing listeners. After sorting sentences by mean percent correct scores, 320
      sentences were assigned to 16 lists of equivalent difficulty. List equivalency
      was then validated by presenting all sentence lists, in a novel random order, to
      adults and children with hearing loss. A final-validation stage examined single
      list comparisons from adult and pediatric listeners tested in research or
      clinical settings. RESULTS: The results of the simulation study allowed for the
      creation of 16 lists of 20 sentences. The average intelligibility of each list
      ranged from 78.4 to 78.7%. List equivalency was then validated, when the results
      of 16 adult cochlear implant users and 9 pediatric hearing aid and cochlear
      implant users revealed no significant differences across lists. The binomial
      distribution model was used to account for the inherent variability observed in
      the lists. This model was also used to generate 95% confidence intervals for one
      and two list comparisons. A retrospective analysis of 361 instances from 78 adult
      cochlear implant users and 48 instances from 36 pediatric cochlear implant users
      revealed that the 95% confidence intervals derived from the model captured 94% of
      all responses (385 of 409). CONCLUSIONS: The cochlear implant simulation was
      shown to be an effective method for estimating the intelligibility of individual
      sentences for use in the evaluation of cochlear implant users. Furthermore, the
      method used for constructing equivalent sentence lists and estimating the
      inherent variability of the materials has also been validated. Thus, the AzBio
      Pediatric Sentence Lists are equivalent and appropriate for the assessment of
      speech-understanding abilities of children with hearing loss as well as adults
      for whom performance on AzBio sentences is near the floor.

PMID- 24658602
TI  - Thyroid endocrine disruption in zebrafish larvae after exposure to mono-(2
      ethylhexyl) phthalate (MEHP).
AB  - Phthalates are extensively used as plasticizers in a variety of daily-life
      products, resulting in widespread distribution in aquatic environments. However,
      limited information is available on the endocrine disrupting effects of
      phthalates in aquatic organisms. The aim of the present study was to examine
      whether exposure to mono-(2-ethylhexyl) phthalate (MEHP), the hydrolytic
      metabolite of di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid endocrine
      system in fish. In this study, zebrafish (Danio rerio) embryos were exposed to
      different concentrations of MEHP (1.6, 8, 40, and 200 MUg/L) from 2 h post
      fertilization (hpf) to 168 hpf. The whole-body content of thyroid hormone and
      transcription of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis
      were examined. Treatment with MEHP significantly decreased whole-body T4 contents
      and increased whole-body T3 contents, indicating thyroid endocrine disruption.
      The upregulation of genes related to thyroid hormone metabolism (Dio2 and UGT1ab)
      might be responsible for decreased T4 contents. Elevated gene transcription of
      Dio1 was also observed in this study, which might assist to degrade increased T3
      contents. Exposure to MEHP also significantly induced transcription of genes
      involved in thyroid development (Nkx2.1 and Pax8) and thyroid hormone synthesis
      (TSHbeta, NIS and TG). However, the genes encoding proteins involved in TH
      transport (transthyretin, TTR) was transcriptionally significantly down-regulated
      after exposure to MEHP. Overall, these results demonstrate that acute exposure to
      MEHP alters whole-body contents of thyroid hormones in zebrafish embryos/larvae
      and changes the transcription of genes involved in the HPT axis, thus exerting
      thyroid endocrine toxicity. 

PMID- 24658603
TI  - Regulation of the demographic structure in isomorphic biphasic life cycles at the
      spatial fine scale.
AB  - Isomorphic biphasic algal life cycles often occur in the environment at ploidy
      abundance ratios (Haploid:Diploid) different from 1. Its spatial variability
      occurs within populations related to intertidal height and hydrodynamic stress,
      possibly reflecting the niche partitioning driven by their diverging adaptation
      to the environment argued necessary for their prevalence (evolutionary
      stability). Demographic models based in matrix algebra were developed to
      investigate which vital rates may efficiently generate an H:D variability at a
      fine spatial resolution. It was also taken into account time variation and type
      of life strategy. Ploidy dissimilarities in fecundity rates set an H:D spatial
      structure miss-fitting the ploidy fitness ratio. The same happened with ploidy
      dissimilarities in ramet growth whenever reproductive output dominated the
      population demography. Only through ploidy dissimilarities in looping rates
      (stasis, breakage and clonal growth) did the life cycle respond to a spatially
      heterogeneous environment efficiently creating a niche partition. Marginal
      locations were more sensitive than central locations. Related results have been
      obtained experimentally and numerically for widely different life cycles from the
      plant and animal kingdoms. Spore dispersal smoothed the effects of ploidy
      dissimilarities in fertility and enhanced the effects of ploidy dissimilarities
      looping rates. Ploidy dissimilarities in spore dispersal could also create the
      necessary niche partition, both over the space and time dimensions, even in
      spatial homogeneous environments and without the need for conditional
      differentiation of the ramets. Fine scale spatial variability may be the key for
      the prevalence of isomorphic biphasic life cycles, which has been neglected so
      far. 

PMID- 24658604
TI  - Protection of quality and innovation in radiation oncology: the prospective
      multicenter trial QUIRO of DEGRO: evaluation of time, attendance of medical
      staff, and resources during radiotherapy with tomotherapy.
AB  - PURPOSE: The technical progress in radiotherapy in recent years has been
      tremendous. This also implies a change of human and time resources. However,
      there is a lack of data on this topic. Therefore, the DEGRO initiated several
      studies in the QUIRO project on this subject. The present publication focuses on
      results for tomotherapy systems and compares them with other IMRT techniques.
      METHODS: Over a period of several months, time allocation was documented using a
      standard form at two university hospitals. The required time for individual steps
      in the treatment planning process was recorded for all involved professional
      groups (physicist, technician, and physician) by themselves. The time monitoring
      at the treatment machines was performed by auxiliary employees (student research
      assistants). Evaluation of the data was performed for all recorded data as well
      as by tumor site. A comparison was made between the two involved institutions.
      RESULTS: A total of 1,691 records were analyzed: 148 from head and neck (H&N)
      tumors, 460 from prostate cancer, 136 from breast cancer, and 947 from other
      tumor entities. The mean value of all data from both centers for the definition
      of the target volumes for H&N tumors took a radiation oncology specialist 75 min,
      while a physicist needed for the physical treatment planning 214 min. For
      prostate carcinomas, the times were 60 and 147 min, respectively, and for the
      group of other entities 63 and 192 min, respectively. For the first radiation
      treatment, the occupancy time of the linear accelerator room was 31, 26, and 30
      min for each entity (H&N, prostate, other entities, respectively). For routine
      treatments 22, 18, and 21 min were needed for the particular entities. Major
      differences in the time required for the individual steps were observed between
      the two centers. CONCLUSION: This study gives an overview of the time and
      personnel requirements in radiation therapy using a tomotherapy system. The most
      representative analysis could be done for the room occupancy times during
      treatment in both centers. Due to the partly small amount of data and differing
      planning workflows between the two centers, it is problematic to draw a firm
      conclusion with regard to planning times. Overall, the time required for the
      tomotherapy treatment and planning is slightly higher compared to other IMRT
      techniques.

PMID- 24658605
TI  - Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast
      cancer.
AB  - BACKGROUND AND PURPOSE: There are scarce data available on the
      prognostic/predictive value of p-Akt and p-mTOR protein expression in patients
      with high-risk early breast cancer. PATIENTS AND METHODS: Formalin-fixed paraffin
      embedded (FFPE) tumor tissue samples from 997 patients participating in two
      adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein
      expression, and PIK3CA mutational status. These markers were evaluated for
      associations with each other and with selected patient and tumor characteristics,
      immunohistochemical subtypes, disease-free survival (DFS), and overall survival
      (OS). RESULTS: p-mTOR protein expression was negatively associated with EGFR and
      positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA
      mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and
      PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p
      Akt473 expression. In univariate analysis, EGFR (p = 0.016) and the coexpression
      of EGFR and p-mTOR (p = 0.015) were associated with poor OS. Among patients with
      p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy
      were associated with decreased risk for both relapse and death (p = 0.013 and p <
      0.001, respectively). In the subgroup of patients with locoregional relapse,
      positive EGFR and mTOR protein expression was found to be associated with
      increased (p = 0.034) and decreased (p < 0.001) risk for earlier relapse,
      respectively. In multivariate analysis, low levels of p-Akt308 and the
      coexpression of EGFR and p-mTOR retained their prognostic value. CONCLUSION: Low
      protein expression of p-Akt308 was associated with improved DFS and OS among
      patients treated with hormonal therapy following adjuvant chemotherapy.
      Coexpression of EGFR and p-mTOR was associated with worse OS.

PMID- 24658606
TI  - Metastatic spinal cord compression: a validated survival score for elderly
      patients.
AB  - BACKGROUND AND PURPOSE: This study aimed to develop a validated survival score
      for elderly patients with metastatic spinal cord compression (MSCC). PATIENTS AND
      METHODS: In all, 1,128 patients were randomly assigned to the test (n = 564) or
      validation group (n = 564). In the test group, ten pretreatment factors (age,
      gender, performance status, primary tumor, number of involved vertebrae,
      ambulatory status, other bone metastases, visceral metastases, interval from
      cancer diagnosis to radiotherapy of MSCC, time to developing motor deficits) plus
      the radiation regimen were retrospectively evaluated. Factors significantly
      associated with survival on multivariate analysis were included in the survival
      score. The score for each factor was determined by dividing the 6-month survival
      rate (%) by 10. The prognostic score represented the sum of the scores for each
      factor. RESULTS: In the multivariate analysis of the test group, age, performance
      status, primary tumor type, ambulatory status, other bone metastases, visceral
      metastases, interval from cancer diagnosis to radiotherapy of MSCC, and time to
      developing motor deficits were significantly associated with survival. Total
      scores ranged from 25 to 57 points. In the test group, 6-month survival rates
      were 11 % for 25-39 points, 56 % for 40-48 points, and 97 % for 49-57 points (p <
      0.001). In the validation group, 6-month survival rates were 10, 53, and 94 %,
      respectively (p < 0.001). CONCLUSION: Based on the survival scores of the test
      group, three prognostic groups were identified. The survival rates of the
      validation group were similar to the test group. This score appears reproducible
      and can help select the appropriate treatment for elderly patients with MSCC.

PMID- 24658607
TI  - Is radiation an effective therapy   in echinococcus multilocularis?

PMID- 24658608
TI  - MYH9 and APOL1 gene polymorphisms and the risk of CKD in patients with lupus
      nephritis from an admixture population.
AB  - MYH9 polymorphisms have been described to be associated with the risk of CKD in
      non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black
      descendants, MHY9 genetic variants could partially explain the excess risk of CKD
      associated with African ancestry. However, recent data suggests that APOL1 gene
      co-segregate with MYH9, and could be the gene truly associated with CKD risk. In
      this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the
      risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective
      analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and
      rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3
      rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained
      both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was
      defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD).
      Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not
      in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9
      polymorphism showed a positive association (HR3.72, 95%CI 1.47-9.38, p = 0.005).
      When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present
      in 29.7% in the PO group vs. 18.5% in controls) showed a significant association
      to the risk of PO, even after adjustments for baseline estimated creatinine
      clearance and autossomal ancestry (HR 2.0, 95%CI 1.2-3.4, p = 0.01). Our results
      show that in our population MYH9, but not APOL1, gene polymorphisms confer an
      increased risk of CKD in LN patients, independently of race. 

PMID- 24658610
TI  - Acute stress rapidly increases the readily releasable pool of glutamate vesicles
      in prefrontal and frontal cortex through non-genomic action of corticosterone.

PMID- 24658609
TI  - Parity and pancreatic cancer risk: a dose-response meta-analysis of epidemiologic
      studies.
AB  - BACKGROUND: Previous epidemiologic studies have reported inconsistent results
      between parity and pancreatic cancer (PC) risk. To our knowledge, a comprehensive
      and quantitative assessment of this association has not been conducted. METHODS:
      Relevant published studies of parity and PC were identified using MEDLINE
      (PubMed) and Web of Science databases until November 2013. Two authors (H-BG and
      LW) independently assessed eligibility and extracted data. Eleven prospective and
      11 case-control studies reported relative risk (RR) estimates and 95% confidence
      intervals (CIs) of PC associated with parity. Fixed- and random-effects models
      were used to estimate the summary RR depending on the heterogeneity of effects.
      RESULTS: The summary RR for PC comparing the highest versus lowest parity was
      0.86 (95% CI: 0.73-1.02; Q = 50.49, P<0.001, I2 = 58.4%). Significant inverse
      associations were also observed in the studies that adjusted for cigarette
      smoking (RR = 0.81; 95% CI: 0.68-0.98), Type 2 diabetes mellitus (RR = 0.83; 95%
      CI: 0.75-0.93), and those that included all confounders or important risk factors
      (RR = 0.85; 95% CI: 0.76-0.96). Additionally, in the dose-response analysis, the
      summary RR for per one live birth was 0.97 (95% CI: 0.94-1.01; Q = 62.83,
      P<0.001, I2 = 69.8%), which also indicated a borderline statistically significant
      inverse effect of parity on PC risk. No evidence of publication bias and
      significant heterogeneity between subgroups were detected by meta-regression
      analyses. CONCLUSION: In summary, these findings suggest that higher parity is
      associated with a decreased risk of PC. Future large consortia or pooled studies
      are warranted to fully adjust for potential confounders to confirm this
      association.

PMID- 24658611
TI  - LcrQ blocks the role of LcrF in regulating the Ysc-Yop type III secretion genes
      in Yersinia pseudotuberculosis.
AB  - Pathogenic Yersinia species employ the Ysc-Yop type III secretion system (T3SS)
      encoded by a highly conserved pYV virulence plasmid to export the virulence
      effectors into host cells. The Ysc-Yop T3SS is tightly regulated by multiple
      contributing proteins that function at different levels. However, systematic
      transcriptional regulation analysis of Ysc-Yop T3SS is lacking and the detailed
      mechanism under this regulation process is still elusive. Aimed at systematically
      characterizing transcriptional regulations of all T3SS genes in Y.
      pseudotuberculosis, we amplified 97 non-coding fragments from the pYV plasmid and
      analyzed transcriptional responses of the T3SS genes under different growth
      conditions. Transcriptions of T3SS genes were induced at 37 degrees C and genes
      encoding T3SS effectors were highly induced by further depletion of Ca2+. The
      temperature induced gene transcription process is mediated by modules encoded on
      the chromosome, while the Ca2+ depletion-induced process is controlled by the
      positive regulatory protein LcrF as well as the negative regulatory protein LcrQ.
      In this process, LcrQ shares the same targets with LcrF and the effect of LcrQ is
      dependent on the presence of LcrF. Furthermore, over-expression of LcrF showed
      the same phenotype as that of the lcrQ mutant strain and intracellular amount
      balance of LcrQ and LcrF is important in T3SS regulation. When the expression
      level of LcrF exceeds LcrQ, expression of the Ysc-Yop T3SS genes is activated and
      vice versa. Together, these data support a model in which LcrQ blocks the
      activation role of LcrF in regulating the transcription of T3SS genes in
      Yersinia. 

PMID- 24658612
TI  - Long-term culture and functionality of pancreatic islets monitored using
      microelectrode arrays.
AB  - Extracellular recording of the glucose-induced electrical activity of mouse
      islets of Langerhans on microelectrode arrays (MEAs) is an innovative and
      powerful tool to address beta-cell (patho-)physiology. In a dual approach we
      tested whether this technique can detect concentration-dependent drug effects as
      well as characterize alterations in beta-cell activity during prolonged culture.
      First we established conditions that allow long-term investigation of beta-cell
      function by recording electrical activity. The results provide the first
      measurements of beta-cell membrane potential oscillations of individual murine
      islets during long-term culture. Oscillations were recorded for up to 34 days
      after islet isolation. Importantly, the glucose dependence of electrical activity
      did not change over a period of one month. Thus we can follow
      electrophysiological changes of individual islets induced by alterations in the
      beta-cell environment over weeks. Second, we used the MEA technique to assay beta
      cell damage induced by oxidative stress and to evaluate appropriate protection
      mechanisms. Oxidative stress plays a key role in the development of type 2
      diabetes mellitus (T2DM). Examination of the acute effects of H2O2 on electrical
      activity showed that the oxidant reduced the electrical activity in a
      concentration-dependent manner. The superoxide dismutase mimetic, tempol,
      protected against the detrimental effects of H2O2. In conclusion, we demonstrated
      that MEA recordings can be used to address disease-related mechanisms and
      protective interventions in beta-cells. In the future, this fundamental work
      should enable the monitoring of the electrical activity of islets of Langerhans
      under controlled ex vivo conditions including long-term exposure to oxidative
      stress, glucolipotoxicity, and other diabetes-inducing agents. 

PMID- 24658614
TI  - Carbon nanocages: a new support material for Pt catalyst with remarkably high
      durability.
AB  - Low durability is the major challenge hindering the large-scale implementation of
      proton exchange membrane fuel cell (PEMFC) technology, and corrosion of carbon
      support materials of current catalysts is the main cause. Here, we describe the
      finding of remarkably high durability with the use of a novel support material.
      This material is based on hollow carbon nanocages developed with a high degree of
      graphitization and concurrent nitrogen doping for oxidation resistance
      enhancement, uniform deposition of fine Pt particles, and strong Pt-support
      interaction. Accelerated degradation testing shows that such designed catalyst
      possesses a superior electrochemical activity and long-term stability for both
      hydrogen oxidation and oxygen reduction relative to industry benchmarks of
      current catalysts. Further testing under conditions of practical fuel cell
      operation reveals almost no degradation over long-term cycling. Such a catalyst
      of high activity, particularly, high durability, opens the door for the next
      generation PEMFC for "real world" application. 

PMID- 24658613
TI  - Betel chewing and arecoline affects eotaxin-1, asthma and lung function.
AB  - BACKGROUND: Betel nut is commonly used in many countries. Despite evidence
      suggesting an association with asthma, few studies have investigated the
      connection between betel nut use and asthma; thus, the underlying mechanism for
      the association with asthma is also unclear. The aim of this study was to
      investigate the association between betel chewing and asthma as well as the
      associations of plasma arecoline (a biomarker for exposure) and eotaxin-1 (a
      potential mediator) with asthma and lung function. METHODS: We recruited 600
      hospital-based asthmatic patients and 1200 age- and gender-matched community
      controls in southern Taiwan. To clarify the mechanism of action for eotaxin-1 in
      the association between betel chewing and asthma, we also designed an in vitro
      experiment to study the functional associations between arecoline exposure and
      eotaxin-1 levels. RESULTS: A significant association was found between asthma and
      current betel chewing (adjusted odds ratio 2.05, 95% CI = 1.12-3.76), which was
      independent of potential confounders but was attenuated following adjustment for
      eotaxin-1. Arecoline and eotaxin-1 levels were positively correlated (Spearman r
      = 0.303, p = 0.02), while arecoline and arecaidine were negatively correlated
      with lung function. Functionally, arecoline alone does not induce eotaxin-1
      release in vitro from dermal and gingival fibroblasts. However, in the presence
      of IL-4 and TNF-alpha, arecoline at 100 MUg/ml induced more eotaxin-1 release
      than arecoline at 0 MUg/ml (2700+/-98 pg/ml vs 1850+/-142 pg/ml, p = 0.01 in
      dermal fibroblast cells, and 1489+/-78 pg/ml vs 1044+/-95 pg/ml, p = 0.03 in
      gingival fibroblast cells, respectively). CONCLUSION: Betel chewing is associated
      with asthma in this population, with arecoline induction of eotaxin-1 supported
      as a plausible causal pathway.

PMID- 24658615
TI  - Flexor carpi radialis tendon ultrasound pictorial essay.
AB  - Disorders of the flexor carpi radialis tendon (FCRt) are often missed even though
      they are a relatively frequent cause of volar radial wrist pain. They can
      manifest as tenosynovitis, tendinopathy, synovial sheath cysts with or without
      scaphoid-trapezoid-trapezium (STT) joint pathology, and partial or complete
      rupture. Because FCRt disorders often present with non-specific symptoms and a
      non-diagnostic clinical examination, imaging is often necessary for accurate
      evaluation and therapeutic planning. Conventional radiography provides good
      visualization of the neighboring bones and joints, as well as rare intratendinous
      calcifications. MRI enables evaluation of the FCRt and adjacent anatomical
      structures with excellent tissue resolution. In comparison, ultrasound (US)
      evaluation of the FCRt is less commonly described in the radiology literature,
      despite its affordability, exquisite soft tissue resolution, and the advantages
      of quick, dynamic diagnostic imaging. This pictorial essay describes and
      demonstrates the normal anatomy of the FCRt, its US examination technique and
      normal US appearance, and US findings of clinically relevant FCRt disorders.

PMID- 24658616
TI  - The Roots of Alzheimer's Disease: Are High-Expanding Cortical Areas
      Preferentially Targeted??.
AB  - Alzheimer's disease (AD) is regarded a human-specific condition, and it has been
      suggested that brain regions highly expanded in humans compared with other
      primates are selectively targeted. We calculated shared and unique variance in
      the distribution of AD atrophy accounted for by cortical expansion between
      macaque and human, affiliation to the default mode network (DMN), ontogenetic
      development and normal aging. Cortical expansion was moderately related to
      atrophy, but a critical discrepancy was seen in the medial temporo-parietal
      episodic memory network. Identification of "hotspots" and "coldspots" of
      expansion across several primate species did not yield compelling evidence for
      the hypothesis that highly expanded regions are specifically targeted.
      Controlling for distribution of atrophy in aging substantially attenuated the
      expansion-AD relationship. A path model showed that all variables explained
      unique variance in AD atrophy but were generally mediated through aging. This
      supports a systems-vulnerability model, where critical networks are subject to
      various negative impacts, aging in particular, rather than being selectively
      targeted in AD. An alternative approach is suggested, focused on the interplay of
      the phylogenetically old and preserved medial temporal lobe areas with more
      highly expanded association cortices governed by different principles of
      plasticity and stability. 

PMID- 24658617
TI  - Analytical calculation of sensing parameters on carbon nanotube based gas
      sensors.
AB  - Carbon Nanotubes (CNTs) are generally nano-scale tubes comprising a network of
      carbon atoms in a cylindrical setting that compared with silicon counterparts
      present outstanding characteristics such as high mechanical strength, high
      sensing capability and large surface-to-volume ratio. These characteristics, in
      addition to the fact that CNTs experience changes in their electrical conductance
      when exposed to different gases, make them appropriate candidates for use in
      sensing/measuring applications such as gas detection devices. In this research, a
      model for a Field Effect Transistor (FET)-based structure has been developed as a
      platform for a gas detection sensor in which the CNT conductance change resulting
      from the chemical reaction between NH3 and CNT has been employed to model the
      sensing mechanism with proposed sensing parameters. The research implements the
      same FET-based structure as in the work of Peng et al. on nanotube-based NH3 gas
      detection. With respect to this conductance change, the I-V characteristic of the
      CNT is investigated. Finally, a comparative study shows satisfactory agreement
      between the proposed model and the experimental data from the mentioned research.

PMID- 24658618
TI  - Samba: a real-time motion capture system using wireless camera sensor networks.
AB  - There is a growing interest in 3D content following the recent developments in 3D
      movies, 3D TVs and 3D smartphones. However, 3D content creation is still
      dominated by professionals, due to the high cost of 3D motion capture
      instruments. The availability of a low-cost motion capture system will promote 3D
      content generation by general users and accelerate the growth of the 3D market.
      In this paper, we describe the design and implementation of a real-time motion
      capture system based on a portable low-cost wireless camera sensor network. The
      proposed system performs motion capture based on the data-driven 3D human pose
      reconstruction method to reduce the computation time and to improve the 3D
      reconstruction accuracy. The system can reconstruct accurate 3D full-body poses
      at 16 frames per second using only eight markers on the subject's body. The
      performance of the motion capture system is evaluated extensively in experiments.

PMID- 24658619
TI  - Adaptive preheating duration control for low-power ambient air quality sensor
      networks.
AB  - Ceramic gas sensors used for measuring ambient air quality have features suitable
      for practical applications such as healthcare and air quality management, but
      have a major drawback-large power consumption to preheat the sensor for accurate
      measurements. In this paper; the adaptive preheating duration control (APC)
      method is proposed to reduce the power consumption of ambient air quality sensor
      networks. APC reduces the duration of unnecessary preheating, thereby alleviating
      power consumption. Furthermore, the APC can allow systems to meet user
      requirements such as accuracy and periodicity factor when detecting the
      concentration of a target gas. A performance evaluation of the power consumption
      of gas sensors is conducted with various user requirements and factors that
      affect the preheating duration of the gas sensor. This shows that the power
      consumption of the APC is lower than that of continuous power supply methods and
      constant power supply/cutoff methods. 

PMID- 24658620
TI  - Estimates of minor ocean tide loading displacement and its impact on continuous
      GPS coordinate time series.
AB  - The site displacement due to ocean tidal loading is regarded as one of the
      largest uncertainties in precise geodetic positioning measurements, among which
      the effect of minor ocean tides (MOT), except for the 11 main tidal constituents,
      are sometimes neglected in routine precise global positioning system (GPS) data
      processing. We find that MOT can cause large vertical loading displacements with
      peak-to-peak variations reaching more than 8 mm at coastal/island stations. The
      impact of MOT on the 24-hour GPS solution is slightly larger than the magnitude
      of MOT loading itself, with peak-to-peak displacement variation at about 10 mm
      for the horizontal and 30 mm for the vertical components. We also find that the
      vertical velocity of all the selected stations in the Southwest Pacific was
      reduced by more than 10% after considering the MOT effect, while stations with
      weighted root mean square reduced data account for 62%, 59%, and 36% for the up,
      east, and north components respectively, in particular for most coastal/island
      stations. Furthermore, MOT correction could significantly reduce the annual
      signal of the global stacked east component, the near fortnightly and the long
      term periodic signals in the up component. The power of some anomalous harmonics
      of 1.04 cycle per year is also decreased to some extent. These results further
      proved the benefits of MOT correction in precise GPS data processing. 

PMID- 24658621
TI  - Improving data quality with an accumulated reputation model in participatory
      sensing systems.
AB  - The ubiquity of mobile devices brings forth a sensing paradigm, participatory
      sensing, to collect and interpret sensory information from the environment.
      Participants join in multifarious sensing tasks and share their data. The sensing
      result can be obtained in light of shared data. It is not uncommon that some
      corrupted data is provided by participants, which makes sensing result unreliable
      accordingly. To address this nontrivial issue, we proposed the accumulated
      reputation model (ARM) to improve the accuracy of the sensing result. In ARM,
      participants' reputation will be computed and accumulated based on their sensing
      data. The sensing data from reputable participants make higher contributions to
      the sensing result. ARM performs well on calculating accurate sensing results,
      even in extreme scenarios, where there are many inexperienced or malicious
      participants. 

PMID- 24658622
TI  - On the acoustic filtering of the pipe and sensor in a buried plastic water pipe
      and its effect on leak detection: an experimental investigation.
AB  - Acoustic techniques have been used for many years to find and locate leaks in
      buried water distribution systems. Hydrophones and accelerometers are typically
      used as sensors. Although geophones could be used as well, they are not generally
      used for leak detection. A simple acoustic model of the pipe and the sensors has
      been proposed previously by some of the authors of this paper, and their model
      was used to explain some of the features observed in measurements. However,
      simultaneous measurements of a leak using all three sensor-types in controlled
      conditions for plastic pipes has not been reported to-date and hence they have
      not yet been compared directly. This paper fills that gap in knowledge. A set of
      measurements was made on a bespoke buried plastic water distribution pipe test
      rig to validate the previously reported analytical model. There is qualitative
      agreement between the experimental results and the model predictions in terms of
      the differing filtering properties of the pipe-sensor systems. A quality measure
      for the data is also presented, which is the ratio of the bandwidth over which
      the analysis is carried out divided by the centre frequency of this bandwidth.
      Based on this metric, the accelerometer was found to be the best sensor to use
      for the test rig described in this paper. However, for a system in which the
      distance between the sensors is large or the attenuation factor of the system is
      high, then it would be advantageous to use hydrophones, even though they are
      invasive sensors. 

PMID- 24658623
TI  - Development of an electrochemical sensing technique for rapid genotyping of
      hepatitis B virus.
AB  - OBJECTIVE: To develop a convenient; sensitive; accurate; and economical technique
      for genotyping of hepatitis B viruses (HBVs). METHODS: The mercapto-modified B1;
      B2; C1; and C2-specific genotyping probes consisted of two probes for each HBV
      genotype that served as a double verification system. These probes were fixed on
      the surface of No. 1; 2; 3; and 4 gold electrodes; respectively; via Au-S bonds.
      Different charge generated by the binding of RuHex to phosphate groups of the DNA
      backbone before and after hybridization was used for distinguishing the different
      genotypes. RESULTS: During hybridization with genotype B; the charges detected at
      the No. 1 and 2 electrodes were significantly increased; while the charge at the
      No. 3 and 4 electrodes did not change significantly. During hybridization with
      genotype C; the charges detected at No. 3 and 4 electrodes were significantly
      increased; while the signals remained unchanged at the No. 1 and 2 electrodes.
      During hybridization with mixed genotypes (B and C); the charges detected at all
      four electrodes were significantly increased. The linear range of detection was
      10(-7) to 10(-10) mol/L and the sensitivity for detecting mixed B (10%) or C
      (10%). CONCLUSIONS: Rapid genotyping of HBVs based on electrochemical sensing is
      simple, has good specificity; and can greatly reduce the cost. This method can be
      used for sensitive detection of mixed B and C HBV genotypes.

PMID- 24658624
TI  - An analytical model for the performance analysis of concurrent transmission in
      IEEE 802.15.4.
AB  - Interference is a serious cause of performance degradation for IEEE802.15.4
      devices. The effect of concurrent transmissions in IEEE 802.15.4 has been
      generally investigated by means of simulation or experimental activities. In this
      paper, a mathematical framework for the derivation of chip, symbol and packet
      error probability of a typical IEEE 802.15.4 receiver in the presence of
      interference is proposed. Both non-coherent and coherent demodulation schemes are
      considered by our model under the assumption of the absence of thermal noise.
      Simulation results are also added to assess the validity of the mathematical
      framework when the effect of thermal noise cannot be neglected. Numerical results
      show that the proposed analysis is in agreement with the measurement results on
      the literature under realistic working conditions. 

PMID- 24658625
TI  - The dual carrier ABSK system based on a FIR bandpass filter.
AB  - The special impacting filter (SIF) with IIR structure has been used to demodulate
      ABSK signals. The key points of SIF, including the resonance circuit's high Q
      value and the "slope-phase discrimination" character of the filter sideband, are
      demonstrated in the paper. The FIR narrow-band bandpass filtering system, which
      can also provide the impact-filtering effect, is proposed. A dual carrier system
      of ABSK signals is designed with the proposed FIR filter as its receiver. The
      simulation results show that the FIR filter can work well. Moreover, compared to
      the traditional SIF, the proposed FIR filter can not only achieve higher spectral
      efficiency, but also give better demodulation performance. 

PMID- 24658626
TI  - A caregiver support platform within the scope of an ambient assisted living
      ecosystem.
AB  - The Ambient Assisted Living (AAL) area is in constant evolution, providing new
      technologies to users and enhancing the level of security and comfort that is
      ensured by house platforms. The Ambient Assisted Living for All (AAL4ALL) project
      aims to develop a new AAL concept, supported on a unified ecosystem and
      certification process that enables a heterogeneous environment. The concepts of
      Intelligent Environments, Ambient Intelligence, and the foundations of the
      Ambient Assisted Living are all presented in the framework of this project. In
      this work, we consider a specific platform developed in the scope of AAL4ALL,
      called UserAccess. The architecture of the platform and its role within the
      overall AAL4ALL concept, the implementation of the platform, and the available
      interfaces are presented. In addition, its feasibility is validated through a
      series of tests. 

PMID- 24658627
TI  - Effect of lenvatinib (E7080) on the QTc interval: results from a  thorough QT
      study in healthy volunteers.
AB  - PURPOSE: QT assessment of oncology drugs is generally challenging because they
      are genotoxic and, of necessity,they require multisite evaluation in cancer
      patients. Lenvatinib is not genotoxic, therefore, this thorough QT (TQT)study
      with lenvatinib, a multityrosine kinase inhibitor, was undertaken utilizing
      healthy volunteers and concentration effect modeling to project the TQT effect at
      high plasma levels. METHODS: Fifty-two healthy subjects randomly received single
      doses of lenvatinib 32 mg, placebo, or moxifloxacin 400 mg in a three-way
      crossover study. Serial electrocardiograms were recorded, and the effect on
      placebo corrected change-from-baseline QTcF (DeltaDeltaQTcF) was evaluated. The
      relationship between lenvatinib plasma concentrations and QTcF was analyzed with
      linear mixed effects modeling. RESULTS: L envatinib mildly lowered the heart rate
      by 5-8 bpm during the first 12 h after dosing. DeltaDeltaQTcF was shortened with
      a peak effect of -5.72 ms (90 % confidence interval (90 % CI) -7.76 to -3.69 ms)
      at 6 h postdosing.The upper bound of mean DeltaDeltaQTcF did not exceed 2 ms at
      any time point postdosing. A concentration-dependent effect of lenvatinib on
      DeltaDeltaQTcF was identified with an estimated population intercept of -2.96 ms
      (90 % CI -4.49 to-1.43 ms; P = 0.0016) and a negative slope of -0.0045(90 % CI 
      4.49 to -1.43) ms per ng/mL, respectively. The safety profile after a single dose
      of lenvatinib was acceptable,with adverse events (AEs) of mild-to-moderate
      severity and no serious AEs. CONCLUSIONS: L envatinib had no clinically relevant
      effect on the QTc interval. Concentration-effect modeling supports the lack of
      QTc prolongation at high plasma concentrations.

PMID- 24658628
TI  - Treatment results and prognostic factors for advanced squamous  cell carcinoma of
      the hypopharynx treated with concurrent  chemoradiotherapy.
AB  - PURPOSE: The purpose of the study is to review our experience with concurrent
      chemoradiotherapy (CCRT) for patients with advanced resectable squamous cell
      carcinoma(SCC) of the hypopharynx and to evaluate the factors affecting survival
      and larynx preservation. STUDY DESIGN: Retrospective study. METHODS AND
      MATERIALS: T he records of 102 patients with Stage III or IV resectable SCC of
      the hypopharynx treated with CCRT between January 1998 and August 2010 were
      reviewed. Of the 102 patients, 62 were treated with high dose regimens including
      cisplatin, 5-fluorouracil, methotrexate, leucovorin or docetaxel, cisplatin, and
      5-fluorouracil. The remaining 40 were treated with low-dose regimens including
      carboplatin and uracil-tegafur, weekly docetaxel, or S-1. Radiotherapy was
      delivered 5 days a week using a single daily fraction of 1.8-2.0 Gray (Gy), to a
      total dose of 64.8-70.2 Gy. Overall survival (OS), disease-specific survival
      (DSS), and DSS with larynx preservation were estimated using Kaplan-Meier
      methods. The log-rank test and Cox proportional hazards regression were used to
      identify significant prognostic factors for OS, DSS, and DSS with larynx
      preservation. RESULTS: The 5-year OS and DSS for all patients treated with CCRT
      were 51.3 and 64.3 %, respectively. The 5-year DSS with larynx preservation was
      55.5 %. On multivariate analysis, the content of chemotherapy was a significant
      predictor of OS and DSS for patients undergoing CCRT ; N stage was a significant
      prognostic factor for DSS and larynx preservation. CONCLUSION: T he treatment
      method including the indication for CCRT may be determined by the contents of the
      chemotherapy and the N stages of SCC of the hypopharynx.

PMID- 24658629
TI  - Phase I and pharmacokinetic study of polymeric  micelle-formulated paclitaxel in
      adult Chinese patients  with advanced solid tumors.
AB  - PURPOSE: Polymeric micelle-formulated paclitaxel (PM paclitaxel) is a nanoscale
      drug delivery compound. This study investigated the maximum tolerated dose (MTD),
      dose-limiting toxicities, and pharmacokinetic (PK) profile of PM paclitaxel in
      Chinese patients with treatment-refractory advanced or relapsed solid tumors.
      METHODS: Dose escalation of PM paclitaxel followed the standard '3 + 3' rule,
      starting at 175 mg/m(2). PM paclitaxel was administered over 3 h every 3 weeks.
      Patients were treated until disease progression, intolerance, death, or consent
      withdrawal. Blood samples were collected for PK testing. RESULTS: A ll 23
      patients were evaluable for toxicity. Neutropenia,neuropathy, and myalgia were
      the most common toxicities; acute hypersensitivity reaction was not observed. One
      of six patients at dose level 4 (350 mg/m(2)) and two of six patients at dose
      level 5 (390 mg/m(2)) developed grade 4 neutropenia. The MTD was 350 mg/m(2). No
      patients discontinued treatment because of neuropathy. Partial response was seen
      in five of 20 patients (25 %) who had response assessment, three of whom had
      prior exposure to taxanes (two were heavily pretreated). Ten patients (50 %)had
      stable disease at cycle 2 and only five patients (25 %) had disease progression.
      The area under the curve and the maximum concentration of paclitaxel increased
      with escalating doses, suggesting that PM paclitaxel has linear PKs. CONCLUSIONS:
      The main dose-limiting toxicity for PM paclitaxel was neutropenia, and the
      recommended dose for phase II study is 300 mg/m(2). PM paclitaxel is superior to
      conventional paclitaxel for its simplified premedication regimen and delivery of
      a higher paclitaxel dose without increased neuropathy.

PMID- 24658630
TI  - Design of protease-resistant pexiganan enhances  antileishmanial activity.
AB  - Antimicrobial peptides are increasingly being explored as alternative agents for
      therapy against the parasitic protozoan Leishmania. Previously, we reported that
      the synthetic magainin analog, pexiganan, induced apoptosis of surface protease
      deficient Leishmania. Here, we report the development of an arginine-rich variant
      of this peptide which has reduced protease susceptibility and enhanced activity
      against wild type Leishmania in vitro. This peptide induces calcium
      delocalization and caspase 3/7 activity indicative of apoptosis, demonstrating
      that structural modification of pexiganan leads to drastic changes in biologic
      activity against Leishmania.

PMID- 24658631
TI  - Imbalance in individual researcher's peer review activities quantified for four
      British Ecological Society journals, 2003-2010.
AB  - Researchers contribute to the scientific peer review system by providing reviews,
      and "withdraw" from it by submitting manuscripts that are subsequently reviewed.
      So far as we are aware, there has been no quantification of the balance of
      individual's contributions and withdrawals. We compared the number of reviews
      provided by individual researchers (i.e., their contribution) to the number
      required by their submissions (i.e. their withdrawals) in a large and anonymised
      database provided by the British Ecological Society. The database covered the
      Journal of Ecology, Journal of Animal Ecology, Journal of Applied Ecology, and
      Functional Ecology from 2003-2010. The majority of researchers (64%) did not have
      balanced contributions and withdrawals. Depending on assumptions, 12% to 44%
      contributed more than twice as much as required; 20% to 52% contributed less than
      half as much as required. Balance, or lack thereof, varied little in relation to
      the number of years a researcher had been active (reviewing or submitting).
      Researchers who contributed less than required did not lack the opportunity to
      review. Researchers who submitted more were more likely to accept invitations to
      review. These finding suggest overall that peer review of the four analysed
      journals is not in crisis, but only due to the favourable balance of over- and
      under-contributing researchers. These findings are limited to the four journals
      analysed, and therefore cannot include researcher's other peer review activities,
      which if included might change the proportions reported. Relatively low effort
      was required to assemble, check, and analyse the data. Broader analyses of
      individual researcher's peer review activities would contribute to greater
      quality, efficiency, and fairness in the peer review system. 

PMID- 24658632
TI  - Visual control of trunk translation and orientation during locomotion.
AB  - Previous studies have suggested distinct control of gait characteristics in the
      anterior-posterior (AP) and medial-lateral (ML) directions in response to visual
      input. Responses were larger to a ML visual stimulus, suggesting that vision
      plays a larger role in stabilizing gait in the ML direction. Here, we
      investigated responses of the trunk during locomotion to determine whether a
      similar direction dependence is observed. We hypothesized that translation of the
      trunk would show a similar ML dependence on vision, but that angular deviations
      of the trunk would show equivalent responses in all directions. Subjects stood or
      walked on a treadmill at 5 km/h while viewing a virtual wall of white triangles
      that moved in either the AP or ML direction according to a broadband input
      stimulus. Frequency response functions between the visual scene motion and trunk
      kinematics revealed that trunk translation gain was larger across all frequencies
      during walking compared with standing. Trunk orientation responses were not
      different from standing at very low frequencies; however, at high frequencies,
      trunk orientation gain was much higher during walking. Larger gains in response
      to ML visual scene motion were found for all trunk movements. Higher gains in the
      ML direction while walking suggest that visual feedback may contribute more to
      the stability of trunk movements in the ML direction. Vision modified trunk
      movement behavior on both a slow (translation) and fast (orientation) time scale
      suggesting a priority for minimizing angular deviations of the trunk. Overall,
      trunk responses to visual input were consistent with the theme that control of
      locomotion requires higher-level sensory input to maintain stability in the ML
      direction.

PMID- 24658633
TI  - Provocative motion causes fall in brain temperature and affects   sleep in rats.
AB  - Neural substrate of nausea is poorly understood, contrasting the wealth of
      knowledge about the emetic reflex. One of the reasons for this knowledge deficit
      is limited number and face validity of animal models of nausea. Our aim was to
      search for new physiological correlates of nausea in rats. Specifically, we
      addressed the question whether provocative motion (40-min rotation at 0.5 Hz)
      affects sleep architecture, brain temperature, heart rate (HR) and arterial
      pressure. Six adult male Sprague-Dawley rats were instrumented for recordings of
      EEG, nuchal electromyographic, hypothalamic temperature and arterial pressure.
      Provocative motion had the following effects: (1) total abolition of REM sleep
      during rotation and its substantial reduction during the first hour post-rotation
      (from 20 +/- 3 to 5 +/- 1.5%); (2) reduction in NREM sleep, both during rotation
      (from 57 +/- 6 to 19 +/- 5%) and during the first hour post-rotation (from 56 +/-
      3 to 41 +/- 9%); (3) fall in the brain temperature (from 37.1 +/- 0.1 to 36.0 +/-
      0.1  degrees C); and (4) reduction in HR (from 375 +/- 6 to 327 +/- 7 bpm);
      arterial pressure was not affected. Ondansetron, a 5-HT3 antagonist, had no major
      effect on all observed parameters during both baseline and provocative motion. We
      conclude that in rats, provocative motion causes prolonged arousing effects,
      however without evidence of sympathetic activation that usually accompanies
      heightened arousal. Motion induced fall in the brain temperature complements and
      extends our previous observations in rats and suggests that similar to humans,
      provocative motion triggers coordinated thermoregulatory response, leading to
      hypothermia in this species.

PMID- 24658634
TI  - Affective motivational direction drives asymmetric frontal hemisphere activation.
AB  - Decades of research have shown that the left- and right-frontal cortical regions
      are asymmetrically involved in affective processing. Specifically, this past work
      has demonstrated that greater left-frontal activation is related to positive
      approach, and greater right-frontal activation is related to negative-withdrawal.
      However, much of this past work confounded motivation and affective valence. The
      current experiment sought to illuminate whether frontal asymmetry is related to
      motivation or affective valence by examining frontal-lateralized late positive
      potentials (f-LPPs) and frontal cortical alpha power activation to approach
      positive, approach-negative, and withdrawal-negative affects in the same
      participants. Results revealed that f-LPPs to approach-positive and approach
      negative pictures were larger in left- (vs. right-) frontal regions, whereas f
      LPPs to withdrawal-negative pictures did not differ between frontal regions. In
      addition, midline LPPs to approach-positive and approach-negative pictures
      related to greater left-frontal cortical activation. Together, these results
      suggest that greater relative left-frontal activation is associated with positive
      and negative approach-motivated states in the same participants. More broadly,
      these results are consistent with conceptual models that asymmetric hemisphere
      activation is related to motivational direction, rather than affective valence.

PMID- 24658636
TI  - Efficacy of valganciclovir plus cytomegalovirus immune globulin for prevention of
      cytomegalovirus disease in high-risk renal transplant recipients.

PMID- 24658635
TI  - A simulation protocol for exercise physiology in Fontan patients using a closed
      loop lumped-parameter model.
AB  - BACKGROUND: Reduced exercise capacity is nearly universal among Fontan patients,
      though its etiology is not yet fully understood. While previous computational
      studies have attempted to model Fontan exercise, they did not fully account for
      global physiologic mechanisms nor directly compare results against clinical and
      physiologic data. METHODS: In this study, we developed a protocol to simulate
      Fontan lower-body exercise using a closed-loop lumped-parameter model describing
      the entire circulation. We analyzed clinical exercise data from a cohort of
      Fontan patients, incorporated previous clinical findings from literature,
      quantified a comprehensive list of physiological changes during exercise,
      translated them into a computational model of the Fontan circulation, and
      designed a general protocol to model Fontan exercise behavior. Using inputs of
      patient weight, height, and if available, patient-specific reference heart rate
      (HR) and oxygen consumption, this protocol enables the derivation of a full set
      of parameters necessary to model a typical Fontan patient of a given body-size
      over a range of physiologic exercise levels. RESULTS: In light of previous
      literature data and clinical knowledge, the model successfully produced realistic
      trends in physiological parameters with exercise level. Applying this method
      retrospectively to a set of clinical Fontan exercise data, direct comparison
      between simulation results and clinical data demonstrated that the model
      successfully reproduced the average exercise response of a cohort of typical
      Fontan patients. CONCLUSION: This work is intended to offer a foundation for
      future advances in modeling Fontan exercise, highlight the needs in clinical data
      collection, and provide clinicians with quantitative reference exercise
      physiologies for Fontan patients.

PMID- 24658638
TI  - Criterion for board certification needs revision.

PMID- 24658637
TI  - Etanercept for psoriasis and psoriatic arthritis in a patient with Charcot-Marie
      Tooth disease.

PMID- 24658639
TI  - The microfluidic puzzle: chip-oriented rapid prototyping.
AB  - We demonstrate a new concept for reconfigurable microfluidic devices from
      elementary functional units. Our approach suppresses the need for patterning,
      soft molding and bonding when details on a chip have to be modified. Our system
      has two parts, a base-platform used as a scaffold and functional modules which
      are combined by 'plug-and-play'. To demonstrate that our system sustains typical
      pressures in microfluidic experiments, we produce droplets of different sizes
      using T-junction modules with three different designs assembled successively on a
      3 * 3 modular scaffold. 

PMID- 24658640
TI  - Innovative magnetic rings for circumferential mucosectomy: preliminary research.
AB  - PURPOSE: To improve the procedures used to treat prolapse and hemorrhoids, novel
      magnetic rings were invented to use in circumferential mucosectomies to avoid the
      disadvantages of stapling techniques. METHODS: Thirty adult pigs were randomly
      divided into three groups: Group A (n = 10), which underwent circumferential
      mucosectomy with novel magnetic rings; Group B (n = 10), which underwent
      circumferential mucosectomy with conventional magnetic rings and Group C (n =
      10), which underwent circumferential mucosectomy with a stapling technique.
      RESULTS: All pigs underwent the operation successfully, and the mean length of
      the procedure was similar among the three groups (p > 0.05). There was no
      bleeding in Group A or Group B, while there was a mean blood loss of 78.32 +/-
      26.03 ml in Group C (p < 0.01). Three cases of anastomotic stenosis were found in
      Group C (3/10); two cases were found in Group B (2/10) and no anastomotic
      stenosis was found in Group A (0/10). The difference between groups A and C was
      statistically significant (p < 0.05). The cost for the magnetic rings in groups A
      and B was noticeably lower than that of the stapling techniques in Group C (20.12
      +/- 3.35 vs. 15.76 +/- 2.92 vs. 550.16 +/- 29.71 US dollars, p < 0.001). The
      magnetic rings in groups A and B were spontaneously discharged from the body with
      the necrotic tissues within 1-2 weeks (8.20 +/- 2.73 vs. 9.31 +/- 3.62 days, p >
      0.05), avoiding the permanent implantation of staples in Group C. The anastomosis
      site in Group A showed a smoother and more rapid healing process than that in
      Group B or C. CONCLUSIONS: The innovative magnetic rings we developed for
      circumferential mucosectomies provide a simple and novel surgical procedure for
      prolapse and hemorrhoids.

PMID- 24658641
TI  - DNA survival and physical and histological properties  of heat-induced
      alterations in burnt bones.
AB  - During forensic casework, it is vital to be able to obtain valuable information
      from burnt bone fragments to ascertain the identity of the victim. Here, we
      report the findings of an experimental study on burnt bovine compact bone
      segments. Compact bones were cut to size and heated in an electric furnace at a
      temperature range of 100-1,100  degrees C with 100  degrees C increments. Heat
      induced alterations to the bone color,weight, volume, and density were monitored
      using gross morphology and micro-focus X-ray computed tomography.We found that
      the increase in temperature caused the color of the compact bones to change in
      order of yellow, brown, gray,and white. In contrast to the weight reduction that
      occurred immediately after burning, we measured no significant reduction in
      volume even at 600  degrees C; however, volume reduced drastically once the
      temperature reached 700  degrees C. Light microscopic histological observations
      of burnt bone revealed heat induced alterations such as cracking and separation
      of the osteons at higher temperatures. In addition to these findings,we sought to
      examine the survival of DNA in the burnt bones using polymerase chain reaction of
      mitochondrial DNA. No amplification was found in the specimens burnt at 250 
      degrees C or higher, indicating the likely difficulty in testing the DNA of burnt
      bones from forensic casework. The results of this study will enable an estimation
      of the burning temperatures of burnt bones found in forensic cases and will
      provide an important framework with which to interpret data obtained during
      anthropological testing and DNA typing.

PMID- 24658642
TI  - Systemic inflammation promotes lung metastasis via E-selectin upregulation in
      mouse breast cancer model.
AB  - Systemic inflammation might modulate the microenvironment in the lungs and
      promotes metastasis. E-selectin, an inflammation inducible endothelial cell
      adhesion molecule, has been reported to play an important role in homing
      metastatic cancer cells. To study the effects of E-selectin expression induced by
      systemic inflammation on breast cancer metastasis, we first treated BALB/c mice
      with lipopolysaccharide (LPS) to induce systemic inflammation. Pulmonary tissues
      were analyzed by wet/dry ratio, hematoxylin and eosin (H&E) staining and
      immunohistochemistry. Then 4T1 cells were injected via tail vein. Lung surface
      metastasis was counted and detected by histological analysis. LPS-induced E
      selectin expression and tumor cells adhesion were assessed by western blotting
      and immunofluorescence. The circulating levels of proinflammatory cytokines in
      sera were evaluated by ELISA. Our results showed that a significant increase in
      breast cancer metastasis to lungs was observed in LPS-treated mice vs. the PBS
      treated mice, accompanying with an increased E-selectin expression in pulmonary
      tissue of LPS-treated mice. In vitro studies showed a significant elevation of E
      selectin production in MPVECs which enhanced the adhesion activity of 4T1 cells.
      Treatment with anti-E-selectin antibody significantly reduced the development of
      metastasis in vivo, and significantly reduced the adhesion of 4T1 cells to MPVECs
      in vitro. Our results suggest that systemic inflammation may increase the
      expression of E-selectin which mediated the lung metastasis of breast cancer in
      mouse model. 

PMID- 24658643
TI  - Ionic liquids from cationic palladium(II) chelate complexes: preparation, thermal
      properties, and crystal structures.
AB  - Metal-containing ionic liquids comprising cationic Pd(II) chelate complexes and
      the bis(trifluoromethanesulfonyl)amide (Tf2N) anion were prepared:
      [Pd(acac)(Me4en)]Tf2N (1), [Pd(acac)(BuMe3en)]Tf2N (2), and [Pd(C8
      acac)(Me4en)]Tf2N (3) (acac = 2,4-pentanedionate, C8-acac = 3-octyl-2,4
      pentanedionate, Me4en = N,N,N',N'-tetramethylethylenediamine, BuMe3en = N-butyl
      N,N',N'-trimethylethylenediamine). These salts were yellow solids with melting
      points of 85.2  degrees C, 71.1  degrees C, and 62.3  degrees C, respectively.
      During cooling from the liquid state, complex 1 exhibited crystallization,
      whereas 2 and 3 exhibited only glass transitions at approximately -40  degrees C.
      X-ray structure determination revealed that the cations in 1 and 3 form dimer
      like arrangements and that there were no direct contacts between the charged
      moieties of the cations and anions in the solid state.

PMID- 24658644
TI  - The dynamics and regulators of cell fate decisions are revealed by pseudotemporal
      ordering of single cells.
AB  - Defining the transcriptional dynamics of a temporal process such as cell
      differentiation is challenging owing to the high variability in gene expression
      between individual cells. Time-series gene expression analyses of bulk cells have
      difficulty distinguishing early and late phases of a transcriptional cascade or
      identifying rare subpopulations of cells, and single-cell proteomic methods rely
      on a priori knowledge of key distinguishing markers. Here we describe Monocle, an
      unsupervised algorithm that increases the temporal resolution of transcriptome
      dynamics using single-cell RNA-Seq data collected at multiple time points.
      Applied to the differentiation of primary human myoblasts, Monocle revealed
      switch-like changes in expression of key regulatory factors, sequential waves of
      gene regulation, and expression of regulators that were not known to act in
      differentiation. We validated some of these predicted regulators in a loss-of
      function screen. Monocle can in principle be used to recover single-cell gene
      expression kinetics from a wide array of cellular processes, including
      differentiation, proliferation and oncogenic transformation. 

PMID- 24658646
TI  - Patient-centered medical home model: do school-based health centers fit the
      model?
AB  - School-based health centers (SBHCs) are an important component of health care
      reform. The SBHC model of care offers accessible, continuous, comprehensive,
      family-centered, coordinated, and compassionate care to infants, children, and
      adolescents. These same elements comprise the patient-centered medical home
      (PCMH) model of care being promoted by the Affordable Care Act with the hope of
      lowering health care costs by rewarding clinicians for primary care services.
      PCMH survey tools have been developed to help payers determine whether a
      clinician/site serves as a PCMH. Our concern is that current survey tools will be
      unable to capture how a SBHC may provide a medical home and therefore be denied
      needed funding. This article describes how SBHCs might meet the requirements of
      one PCMH tool. SBHC stakeholders need to advocate for the creation or
      modification of existing survey tools that allow the unique characteristics of
      SBHCs to qualify as PCMHs. 

PMID- 24658645
TI  - Real-time imaging of oxidative and nitrosative stress in the liver of live
      animals for drug-toxicity testing.
AB  - Current drug-safety assays for hepatotoxicity rely on biomarkers with low
      predictive power. The production of radical species, specifically reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), has been proposed as an early
      unifying event linking the bioactivation of drugs to hepatotoxicity and as a more
      direct and mechanistic indicator of hepatotoxic potential. Here we present a
      nanosensor for rapid, real-time in vivo imaging of drug-induced ROS and RNS for
      direct evaluation of acute hepatotoxicity. By combining fluorescence resonance
      energy transfer (FRET) and chemiluminescence resonance energy transfer (CRET),
      our semiconducting polymer-based nanosensor simultaneously and differentially
      detects RNS and ROS using two optically independent channels. We imaged drug
      induced hepatotoxicity and its remediation longitudinally in mice after systemic
      challenge with acetaminophen or isoniazid. We detected dose-dependent ROS and RNS
      activity in the liver within minutes of drug challenge, which preceded
      histological changes, protein nitration and DNA double-strand-break induction. 

PMID- 24658647
TI  - Patient turnover and nursing employment in Massachusetts hospitals before and
      after health insurance reform: implications for the Patient Protection and
      Affordable Care Act.
AB  - The Affordable Care Act is modeled after Massachusetts insurance reforms enacted
      in 2006. A linear mixed effect model examined trends in patient turnover and
      nurse employment in Massachusetts, New York, and California nonfederal hospitals
      from 2000 to 2011. The linear mixed effect analysis found that the rate of
      increase in hospital admissions was significantly higher in Massachusetts
      hospitals (p<.001) than that in California and New York (p=.007). The rate of
      change in registered nurses full-time equivalent hours per patient day was
      significantly less (p=.02) in Massachusetts than that in California and was not
      different from zero. The rate of change in admissions to registered nurses full
      time equivalent hours per patient day was significantly greater in Massachusetts
      than California (p=.001) and New York (p<.01). Nurse staffing remained flat in
      Massachusetts, despite a significant increase in hospital admissions. The
      implications of the findings for nurse employment and hospital utilization
      following the implementation of national health insurance reform are discussed.

PMID- 24658648
TI  - Cooperative wrapping of nanoparticles by membrane tubes.
AB  - The bioactivity of nanoparticles crucially depends on their ability to cross
      biomembranes. Recent simulations indicate the cooperative wrapping and
      internalization of spherical nanoparticles in tubular membrane structures. In
      this article, we systematically investigate the energy gain of this cooperative
      wrapping by minimizing the energies of the rotationally symmetric shapes of the
      membrane tubes and of membrane segments wrapping single particles. We find that
      the energy gain for the cooperative wrapping of nanoparticles in membrane tubes
      relative to their individual wrapping as single particles strongly depends on the
      ratio rho/R of the particle radius R and the range rho of the particle-membrane
      adhesion potential. For a potential range of the order of one nanometer, the
      cooperative wrapping in tubes is highly favorable for particles with a radius of
      tens of nanometers and intermediate adhesion energies, but not for particles that
      are significantly larger. 

PMID- 24658649
TI  - Association between MTHFR C677T and A1298C polymorphisms and NSCL/P risk in
      Asians: a meta-analysis.
AB  - OBJECTIVE: Several studies have reported the association between
      methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and
      nonsyndromic cleft lip with or without palate (NSCL/P) in Asian populations.
      However, findings have been conflicting. In order to investigate the association,
      a meta-analysis was performed. METHODS: We searched Pubmed, MedLine and EmBase
      database to selected eligible studies. The pooled odds ratios (ORs) with 95%
      confidence intervals (95%CIs) were calculated using fixed effects model or random
      effects model to assess the association between MTHFR polymorphisms and NSCL/P in
      both Asian children and mothers. RESULTS: Finally, nine case-control studies were
      included. Overall, the MTHFR C677T polymorphism and NSCL/P showed pooled ORs
      (95%CI) of 1.41(1.23-1.61) in Asian children, and 1.70(1.19-2.42) in Asian
      mothers. Subgroup analyses by geographical locations further identified the
      association in Eastern Asian children, Western/Central Asian children and
      mothers, but not in Eastern Asian mothers. However, no significant relationship
      between MTHFR A1298C polymorphism and NSCL/P was found in this meta-analysis.
      CONCLUSIONS: The MTHFR 677T allele was associated with an increased risk of
      NSCL/P in Asian populations.

PMID- 24658650
TI  - A novel peptide that inhibits E2F transcription and regresses prostate tumor
      xenografts.
AB  - E2F-1, a key transcription factor necessary for cell growth, DNA repair and
      differentiation, is an attractive target for development of useful anticancer
      drugs in tumors that are E2F "oncogene addicted". A peptide, isolated from phage
      clones, based on its binding to an E2F-1 consensus sequence, was cytotoxic
      against a wide range of cancer cell lines. The peptide was coupled to penetratin
      (PEP) and tested against prostate cancer cell lines, and a fresh sample from a
      patient with metastatic cancer. As the PEP was found to be relatively unstable in
      serum, it was encapsulated in PEGylated liposomes for in vivo studies. The
      peptide was cytotoxic against prostate cell lines and a fresh sample from a
      patient with metastatic prostate cancer. Treatment of mice bearing the human Du
      145 human prostate tumor with the PEP encapsulated in PEGylated liposomes (PL
      PEP) caused tumor regression without significant toxicity. The liposome
      encapsulated PEP has promise as an antitumor agent, alone or in combination with
      inhibitors of DNA synthesis. 

PMID- 24658651
TI  - The optimal extent of lymph node dissection for adenocarcinoma of the
      esophagogastric junction differs between Siewert type II and Siewert type III
      patients.
AB  - BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG)
      has been increasing worldwide. We investigated the clinicopathological
      characteristics of patients with Siewert type II and III AEGs and clarified the
      optimal intra-abdominal lymph node dissection in these patients. METHODS: This
      study included 132 patients with AEG who underwent curative resection at Shizuoka
      Cancer Center from September 2002 to December 2012. We used the index of
      estimated benefit from lymph node dissection (IEBLD) to assess the efficacy of
      lymph node dissection of each station. The clinicopathological characteristics
      and IEBLDs of each station were compared between patients with Siewert type II
      and III AEGs. RESULTS: We analyzed 92 patients with Siewert type II AEG and 40
      patients with Siewert type III AEG. The incidence of lymph node metastasis was
      high in both groups (64.1 % in type II AEG and 75.0 % in type III AEG). The 5
      year survival rates were similar for the patients with Siewert type II and III
      AEGs, at 54.0 and 53.4 %, respectively. The IEBLDs of stations located near the
      esophagogastric junction were generally high in both groups, while the IEBLDs of
      lower perigastric lymph nodes were higher in Siewert type III than in Siewert
      type II AEG cases. CONCLUSIONS: The IEBLDs were similar between Siewert type II
      and III AEGs at all stations except for lower perigastric lymph nodes. Total
      gastrectomy should be selected as a standard treatment for Siewert type III AEG,
      whereas in Siewert type II AEG, preservation of the distal part of the stomach
      may be an acceptable procedure.

PMID- 24658652
TI  - Apoptosis and KI 67 index correlate with preoperative  chemotherapy efficacy and
      better predict the survival  of gastric cancer patients with combined therapy.
AB  - PURPOSE: T he correlation of apoptotic and proliferation index with preoperative
      chemotherapy efficacy was investigated. Their prognostic value was also explored.
      METHODS: 167 patients were enrolled, curative gastrectomy and D2 lymphadenectomy
      were performed, and a total of 12 cycles of perioperative mFOLFOX7 chemotherapy
      was recommended. Apoptosis index (AI) and Ki67 index (KI) in surgical specimens
      were detected. RESULTS: Apoptosis index, KI and AI/KI were significantly
      different between patients received perioperative chemotherapy and surgery (CS
      group, n = 84) and those who received only surgery and postoperative chemotherapy
      (S group, n = 83). In the CS group, number of patients who received 2, 4, 6
      cycles of preoperative chemotherapy were, respectively, 28, 53 and 3. AI, KI and
      AI/KI were closely related to pathological response. Cutoff value of AI and AI/KI
      for response separated CS group patients into two subgroups with significant
      different prognosis and picked up more potential responders than pathological
      evaluation, especially in pathological response evaluation grade 1a-b.
      CONCLUSIONS: Apoptosis index, KI and AI/KI are significantly related to
      chemotherapy efficacy and prognosis of gastric cancer patients who received
      perioperative chemotherapy and radical gastrectomy. They could be used in
      combination with pathological response evaluation to distinguish more potential
      responders.

PMID- 24658653
TI  - Thermally induced apoptosis, necrosis, and heat shock protein expression in 3D
      culture.
AB  - This study was conducted to compare the heat shock responses of cells grown in 2D
      and 3D culture environments as indicated by the level of heat shock protein 70
      expression and the incidence of apoptosis and necrosis of prostate cancer cell
      lines in response to graded hyperthermia. PC3 cells were stably transduced with a
      dual reporter system composed of two tandem expression cassettes-a conditional
      heat shock protein promoter driving the expression of green fluorescent protein
      (HSPp-GFP) and a cytomegalovirus (CMV) promoter controlling the constitutive
      expression of a "beacon" red fluorescent protein (CMVp-RFP). Two-dimensional and
      three-dimensional cultures of PC3 prostate cancer cells were grown in 96-well
      plates for evaluation of their time-dependent response to supraphysiological
      temperature. To induce controlled hyperthermia, culture plates were placed on a
      flat copper surface of a circulating water manifold that maintained the specimens
      within +/-0.1 degrees C of a target temperature. Hyperthermia protocols included
      various combinations of temperature, ranging from 37 degrees C to 57 degrees C,
      and exposure times of up to 2 h. The majority of protocols were focused on
      temperature and time permutations, where the response gradient was greatest. Post
      treatment analysis by flow cytometry analysis was used to measure the incidences
      of apoptosis (annexin V-FITC stain), necrosis (propidium iodide (PI) stain), and
      HSP70 transcription (GFP expression). Cells grown in 3D compared with 2D culture
      showed reduced incidence of apoptosis and necrosis and a higher level of HSP70
      expression in response to heat shock at the temperatures tested. Cells responded
      differently to hyperthermia when grown in 2D and 3D cultures. Three-dimensional
      culture appears to enhance survival plausibly by activating protective processes
      related to enhanced-HSP70 expression. These differences highlight the importance
      of selecting physiologically relevant 3D models in assessing cellular responses
      to hyperthermia in experimental settings.

PMID- 24658654
TI  - Clinical, angiographic and radiographic outcome differences among mechanical
      thrombectomy devices: initial experience of a large-volume center.
AB  - BACKGROUND AND PURPOSE: Higher reperfusion rates have been established with
      endovascular treatment of acute ischemic stroke (AIS). There are limited data on
      the comparative performance of mechanical thrombectomy devices. METHODS: A
      retrospective single-center analysis was undertaken of all consecutive patients
      who underwent thrombectomy using Merci, Penumbra or stent retrievers (SR) from
      September 2010 to November 2012. Baseline characteristics, rates of successful
      recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) score 2b-3),
      symptomatic intracerebral hemorrhage (sICH), final infarct volume, 90-day
      mortality and independent functional outcomes at 90 days were compared across the
      three devices. RESULTS: Our cohort included 287 patients. There were mild
      imbalances in baseline characteristics with trends towards higher National
      Institutes of Health Stroke Scale (NIHSS) score in patients in the Merci group
      (SR=18 vs Merci=21 vs Penumbra=19, p=0.06) and lower Alberta Stroke Program Early
      CT Score (ASPECTS) in patients in the SR group (>7: SR=51% vs Merci=61% vs
      Penumbra=62%, p=0.12). On univariate analysis there were no differences in the
      rate of sICH (SR=7% vs Merci=7% vs Penumbra=6%, p=0.921) and infarct volume
      (SR=61.5 mL vs Merci=69.5 mL vs Penumbra=59.2 mL, p=0.621). Trends towards better
      functional outcomes were found with Penumbra and SR vs Merci (41% vs 36% vs 25%,
      respectively, p=0.079). Complete or near complete reperfusion (mTICI 2b-3) was
      higher in the SR and Penumbra groups than in the Merci group (86% vs 78% vs 70%,
      respectively, p=0.027). Binary logistic regression showed that SR was an
      independent predictor of good functional outcome (OR 2.27, 95% CI 1.018 to 5.048;
      p=0.045). CONCLUSIONS: Although our initial data confirm the superiority of SR
      technology over the Merci device, there was no significant difference in near
      complete/complete reperfusion, final infarct volumes or clinical outcomes between
      SR and Penumbra thromboaspiration.

PMID- 24658655
TI  - Endovascular coiling versus parent artery occlusion for treatment of cavernous
      carotid aneurysms: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Endosaccular coil embolization and parent artery
      occlusion (PAO) are established endovascular techniques for treatment of
      cavernous carotid aneurysms. We performed a systematic review of published series
      on endovascular treatment of cavernous carotid aneurysms to determine outcomes
      and complications associated with endovascular coiling and PAO of cavernous
      carotid artery aneurysms. METHODS: In September 2013, we conducted a computerized
      search of MEDLINE and EMBASE for reports on endovascular treatment of
      intracranial cavernous carotid aneurysms from January 1990 to August 2013.
      Comparisons were made in periprocedural complications and outcomes between
      coiling and PAO patients who did not receive bypass. Event rates were pooled
      across studies using random effects meta-analysis. RESULTS: 20 studies with 509
      patients and 515 aneurysms were included in this systematic review. Aneurysm
      occlusion rates at >3 months after operation were significantly higher in the PAO
      without bypass group (93.0%, 95% CI 86.0 to 97.0) compared with the coiling group
      (67.0%, 95% CI 55.0 to 77.0) (p<0.01). Retreatment rates were significantly lower
      in the PAO without bypass group (6.0%, 95% CI 2.0 to 12.0) compared with the
      coiling group (18.0%, 95% CI 12.0 to 26.0) (p=0.01). Coiling patients had a
      similar morbidity rate (3.0%, 95% CI 2.0 to 6.0) compared with PAO without bypass
      patients (7.0%, 95% CI 3.0 to 12.0) (p=0.13). Coiling patients had a similar
      mortality rate (0.0%, 95% CI 0.0 to 6.0) compared with PAO without bypass
      patients (4.0%, 95% CI 1.0 to 9.0) (p=0.68). CONCLUSIONS: Evidence from non
      comparative studies suggests that traditional endovascular options are highly
      effective in treating cavernous sinus aneurysms. PAO is associated with a higher
      rate of complete occlusion. Periprocedural morbidity and mortality rates are not
      negligible, especially in patients receiving PAO.

PMID- 24658656
TI  - High concentrations of methyl fluoride affect the bacterial community in a
      thermophilic methanogenic sludge.
AB  - To precisely control the application of methyl fluoride (CH3F) for analysis of
      methanogenic pathways, the influence of 0-10% CH3F on bacterial and archaeal
      communities in a thermophilic methanogenic sludge was investigated. The results
      suggested that CH3F acts specifically on acetoclastic methanogenesis. The
      inhibitory effect stabilized at an initial concentration of 3-5%, with around 90%
      of the total methanogenic activity being suppressed, and a characteristic of
      hydrogenotrophic pathway in isotope fractionation was demonstrated under this
      condition. However, extended exposure (12 days) to high concentrations of CH3F
      (>3%) altered the bacterial community structure significantly, resulting in
      increased diversity and decreased evenness, which can be related to acetate
      oxidation and CH3F degradation. Bacterial clone library analysis showed that
      syntrophic acetate oxidizing bacteria Thermacetogenium phaeum were highly
      enriched under the suppression of 10% CH3F. However, the methanogenic community
      did not change obviously. Thus, excessive usage of CH3F over the long term can
      change the composition of the bacterial community. Therefore, data from studies
      involving the use of CH3F as an acetoclast inhibitor should be interpreted with
      care. Conversely, CH3F has been suggested as a factor to stimulate the enrichment
      of syntrophic acetate oxidizing bacteria. 

PMID- 24658657
TI  - Heme oxygenase-1 induction improves cardiac function following myocardial
      ischemia by reducing oxidative stress.
AB  - BACKGROUND: Oxidative stress plays a key role in exacerbating diabetes and
      cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is
      cytoprotective, but its role in post myocardial infarction (MI) and diabetes is
      not fully characterized. We aimed to investigate the protection and the
      mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in
      diabetic mice subjected to LAD ligation. METHODS: In vitro: cultured
      cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin
      protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated
      streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h.
      Cardiac function, histology, biochemical damage markers and signaling pathways
      were measured. RESULTS: HO-1 induction lowered release of lactate dehydrogenase
      (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining,
      improved cell morphology and preserved mitochondrial membrane potential in
      cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non
      diabetic mice (35+/-1%vs.41+/-2, respectively p<0.05). CoPP-treated diabetic
      animals improved cardiac function (43+/-2% p<0.01), reduced CK, Troponin T levels
      and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01
      respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in
      diabetic animals, as indicated by the decrease in superoxide levels in cardiac
      tissues and plasma TNFalpha levels (p<0.05). The increased levels of HO-1 by CoPP
      treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the
      antiapoptotic process (p<0.05). CoPP significantly increased the expression
      levels of pAKT and pGSK3beta (p<0.05) in cardiomyocytes and in diabetic mice with
      MI. SnPP abolished CoPP's cardioprotective effects. CONCLUSIONS: HO-1 induction
      plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in
      reducing post ischemic cardiac damage in the diabetic heart as proved by the
      increased levels of pAKT with a concomitant inhibition of pGSK3beta leading to
      preserved mitochondrial membrane potential.

PMID- 24658658
TI  - Influence of formulation ratio of the plant components  on the antimalarial
      properties of MAMA decoction.
AB  - Mangifera indica, Alstonia boonei, Morinda lucida and Azadirachta indica (MAMA)
      decoction, commonly prepared and used in Nigeria from 1:1:1:1 ratio of Mangifera
      indica L. (Anacardiaceae), Alstonia boonei De Wild (Apocynaceae), Morinda lucida
      Benth (Rubiaceae), and Azadirachta indica A. Juss (Meliaceae) leaves, plus four
      new variants of this combination were subjected to three in vivo antimalarial
      test models using chloroquine-sensitive Plasmodium berghei berghei to determine
      the most active under each of the test models. Using the original formulation,
      MAMA (1:1:1:1) which gave ED50 and ED90 of 101.54+/-2.95 and 227.18+/-2.95,
      respectively, as reference for comparison, MAMA-1 (1:2:2:2), with 79.58+/-1.30
      and 170.98+/-1.30, gave significantly (p<0.05) higher survival at 85 and 340
      mg/kg when 80 % of the mice survived for 15.6 and 17.8 days, respectively, while
      MAMA-2 (2:1:2:2), with 83.57+/-1.93 and 164.23+/-1.93, gave comparable survival
      except at 170 mg/kg with 60 % survivors for 12 days. MAMA-1 and MAMA-2 were the
      best curative formulations with MAMA-1 giving additional prophylactic activity.
      MAMA-3 (2:2:2:1) with 98.70+/-0.91 and 220.17+/-0.91, gave comparable (p>0.05)
      survival at 85 mg/kg with 60 % survival for 13.2 days and significantly higher
      survival at 42.5 mg/kg for 17 days with 40 % survival. Both MAMA and MAMA-3 were
      the best chemosuppressive formulations plus additional curative activities. MAMA
      4 (1:1:2:2), the best prophylactic formulation with 94.87+/-2.43 and 201.20+/
      2.43 gave significantly higher (p<0.05) survival at all doses except at 21.25
      mg/kg which gave 60 % survival up to 10 days. Thus, the antimalarial therapy
      desired, following appropriate diagnosis, whether prophylactic, chemosuppressive
      or curative would determine which of the MAMA decoction formulations to be
      prescribed. This phenomenon of formulary optimization may also be applied to
      other pharmacological activities.

PMID- 24658659
TI  - A breath of new life into human social cognition.
AB  - Sniffing has historically been considered an olfactory behavior because
      inhalation is a necessary step in odor perception. Growing evidence, however, has
      demonstrated that the display of sniffing surpasses the bounds of those contexts
      that are olfactory in nature. In this issue of Chemical Senses, Arzi, Shedlesky,
      Secundo, and Sobel demonstrate that humans mimic visually and auditory-observed
      sniffing, independent of experimentally applied olfactory sensory input. These
      findings raise important and exciting questions about the possible roles of
      sniffing in the social context and highlight the need for chemosensory
      researchers to reconsider the significance of sniffing. 

PMID- 24658660
TI  - Nocturnal manifestations of Parkinson's disease and atypical Parkinsonism.

PMID- 24658661
TI  - REM sleep behavior disorder in Parkinson's disease.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder
      characterized by loss of normal muscle atonia during REM sleep with recurrent
      dream enactment and excessive motor activity. It is a frequent feature in
      patients with Parkinson's disease (PD) and other alpha-synucleinopathies, and can
      occur at any stage of the disease. RBD could be considered a premotor clinical
      manifestation, and can antedate by many years the motor symptomatology. The
      prognostic value of RBD for the risk of developing PD still needs to be
      established. This review article focuses on the clinical aspects, screening and
      diagnostic criteria as well as therapeutic aspects of RBD in PD patients.
      Pathophysiological pathways are also briefly reviewed.

PMID- 24658662
TI  - Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and
      review of the literature.
AB  - Episodic ataxia type 2 (EA2) is an autosomal dominant inherited neurological
      disorder that is characterized by paroxysmal episodes of ataxia. The causative
      gene for EA2 is CACNA1A which codes for the alpha 1A subunit of the voltage-gated
      P/Q-type calcium channel (Cav2.1). We detected a novel point mutation in the
      CACNA1A gene in a large Austrian family. All ten affected family members harbored
      a heterozygous c.3089+2T>C nucleotide exchange in intron 19. In silico modeling
      demonstrated a loss of the splice site of exon 19 by the mutation, which most
      likely results in exon skipping without frameshifting or use of an alternative
      splice site.Clinically, the family exhibited frequent ataxic episodes accompanied
      by headache in some individuals, which showed a good treatment response to
      acetazolamide or aminopyridine. Interictal phenotype variability was high ranging
      from an unremarkable clinical examination to a progressive cerebellar syndrome.
      Detailed cognitive testing with standardized neuropsychological tests revealed
      specific deficits in various domains including memory,executive functions and
      visual abilities. Moreover, a striking coincidence of socio-phobic behavior and
      anxiety disorders was detected within this family, which interfered with
      activities of daily living and has to be taken in consideration in EA2 patient
      management. We here characterize the phenotype of this novel CACNA1A
      mutation,review the respective literature and discuss implications on diagnosis
      and patient management.

PMID- 24658663
TI  - Long-term follow-up of 62 patients with myositis.
AB  - The aim of this work is to evaluate disease-related mortality and the course of
      the disease including functional outcome and quality of life. We did a follow-up
      study on a large prospective cohort of 62 patients with subacute-onset idiopathic
      inflammatory myopathy (IIM) (dermatomyositis (n = 24), nonspecific myositis (n =
      34), necrotizing autoimmune myopathy (n = 4)) after treatment with
      corticosteroids only (randomized controlled trial comparing daily high-dosage
      prednisone with pulse therapy of dexamethasone). Development of connective tissue
      disease (CTD) or malignancy, disease course and mortality, functional outcome and
      quality of life were evaluated. After a mean follow-up of 3 years (SD 1.5), 22 %
      had developed a CTD and 17 % a malignancy. Disease-related mortality was 15 %. A
      monophasic disease course was found in 27 %. Most patients had a chronic (35 %)
      or polyphasic disease (35 %) course and experienced single or multiple relapses.
      Sixteen patients (33 %) were off medication after a mean of 1 year of treatment.
      Disability scores improved particularly in the first 18 months. At follow-up, 68
      % still perceived disabilities. Quality of life scores as measured by the short
      form (SF)-36 improved in the first 18 months. After 18 months, scores remained
      stable during the next years of follow-up and remained low compared to a normal
      population. (1) Two-thirds of the patients with an IIM have a polyphasic or
      chronic disease course and need maintenance treatment. (2) The impact on
      functional outcome and quality of life is considerable and does not improve
      further after 18 months.

PMID- 24658664
TI  - Acquired hemophilia A: an underdiagnosed, severe bleeding disorder.
AB  - Acquired hemophilia is a rare bleeding disorder caused by autoantibodies that
      inhibit coagulation factor VIII. In most cases, it manifests with severe, often
      life-threatening bleeds. Acquired hemophilia may be idiopathic or secondary to
      another condition, most commonly other autoimmune disease or cancer. Treatment is
      directed to stop bleeding and eradicate inhibitory autoantibodies. Like in most
      life-threatening conditions, early diagnosis and treatment are essential for good
      prognosis. Prompt diagnosis and treatment of acquired hemophilia are constantly
      improving owing to the increasing availability of laboratory diagnostic tests and
      growing awareness of physicians of various specialties. 

PMID- 24658665
TI  - New agents for prostate cancer.
AB  - The therapeutic landscape of metastatic castration-resistant prostate cancer
      (mCRPC) has been revolutionized by the arrival of multiple novel agents in the
      past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis
      inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic
      agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded
      incremental extensions of survival and have been recently approved. A number of
      other agents appear promising in early studies, suggesting that the armamentarium
      against castrate-resistant prostate cancer is likely to continue to expand.
      Emerging androgen pathway inhibitors include androgen synthesis inhibitors
      (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain
      inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents
      that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone).
      Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor
      (ipilimumab). Biologic agents targeting the molecular drivers of disease are also
      being investigated as single agents, including cabozantinib (Met and VEGFR2
      inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite
      the disappointing results seen from studies evaluating docetaxel in combination
      with other agents, including GVAX, anti-angiogentic agents (bevacizumab,
      aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin
      receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101),
      the results from the trial evaluating docetaxel in combination with the clusterin
      antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of
      discovering new targets, understanding resistance mechanisms, the optimal
      sequencing and combinations of available agents, as well as biomarkers predictive
      for benefit. Novel agents targeting bone metastases are being developed following
      the success of zoledronic acid and denosumab. Finally, all of these modalities do
      not appear curative, suggesting that clinical trial enrollment and a better
      understanding of biology remain of paramount importance. 

PMID- 24658666
TI  - Structural shimming for high-resolution nuclear magnetic resonance spectroscopy
      in lab-on-a-chip devices.
AB  - High-resolution proton NMR spectroscopy is well-established as a tool for
      metabolomic analysis of biological fluids at the macro scale. Its full potential
      has, however, not been realised yet in the context of microfluidic devices. While
      microfabricated NMR detectors offer substantial gains in sensitivity, limited
      spectral resolution resulting from mismatches in the magnetic susceptibility of
      the sample fluid and the chip material remains a major hurdle. In this
      contribution, we show that susceptibility broadening can be avoided even in the
      presence of substantial mismatch by including suitably shaped compensation
      structures into the chip design. An efficient algorithm for the calculation of
      field maps from arbitrary chip layouts based on Gaussian quadrature is used to
      optimise the shape of the compensation structure to ensure a flat field
      distribution inside the sample area. Previously, the complexity of microfluidic
      NMR systems has been restricted to simple capillaries to avoid susceptibility
      broadening. The structural shimming approach introduced here can be adapted to
      virtually any shape of sample chamber and surrounding fluidic network, thereby
      greatly expanding the design space and enabling true lab-on-a-chip systems
      suitable for high-resolution NMR detection. 

PMID- 24658667
TI  - Hydrogen sulfide improves left ventricular function in smoking rats via
      regulation of apoptosis and autophagy.
AB  - The present study was designed to investigate the protective effects of hydrogen
      sulfide (H2S) against cigarette smoking-induced left ventricular dysfunction in
      rats. Left ventricular structure and function were assessed using two-dimensional
      echocardiography. Cardiomyocyte apoptosis was determined by Annexin V/PI and
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining.
      Cardiac autophagy was evaluated by detection of autophagy-related protein
      expression and observation of autophagosomes. Our results indicated that
      administration of NaHS (a donor of H2S) could protect against smoking-induced
      left ventricular systolic dysfunction. H2S was found to exert anti-apoptotic
      effects in the myocardium of smoking rats by inhibiting JNK and P38 mitogen
      activated protein kinases pathways and activating PI3K/Akt signaling. Moreover,
      H2S could also reduce smoking-induced autophagic cell death via regulation of
      AMPK/mTOR signaling pathway. In conclusion, our study demonstrates that H2S can
      improve left ventricular systolic function in smoking rats via regulation of
      apoptosis and autophagy.

PMID- 24658668
TI  - [The Public Health Service, antibiotic resistance and hospital hygiene].

PMID- 24658669
TI  - [Surveillance of antibiotic consumption in hospitals: tasks of the Public Health
      Service].
AB  - According to the German Protection Against Infection Act (IfSG; section 23
      paragraph 4, July 2011), hospitals and clinics for ambulatory surgery are obliged
      to establish a continuous monitoring of antibiotic consumption in their
      institute. The introduction of the surveillance of antibiotic consumption aims to
      contribute to an optimization of antibiotic prescription practices in order to
      confine the development and spread of resistant pathogens. The local public
      health authority is entitled to supervise the implementation of legal
      requirements in the hospital setting. The main aim of this article is to support
      local public health authorities in coping with this task by providing background
      information on the surveillance of antibiotic consumption and its role as a key
      component of antibiotic stewardship programs. Furthermore, criteria suitable for
      assessing the implementation of a functioning surveillance system are proposed.
      The possibilities and limitations of the activities of public health authorities
      in this context are addressed. 

PMID- 24658670
TI  - [Prevalence of carbapenemase-producing bacteria in hospitals in Saxony, Germany].
AB  - The presence of pathogenic bacteria with acquired carbapenem resistance
      constitutes an increasing problem for infection control and infectious disease
      management. Prompted by an outbreak of infections with Klebsiella pneumoniae
      producing the carbapenemase KPC-2 at a hospital in Saxony, the Saxon State
      Ministry of Social Affairs and Consumer Protection (SMS) initiated a point
      prevalence survey for carbapenemase-producing gram-negative bacteria. Wards at 53
      hospitals in Saxony, mainly intensive care units, were investigated between
      October 2012 and February 2013. Stool samples and rectal swabs of 1,037 patients
      were analyzed for the presence of bacteria with resistance against four major
      groups of antibiotics (4MRGN). Carbapenemase producers were detected in 3
      patients [0.3% CI95 (0.0596; 0.843)] and carbapenem-resistant bacteria without
      carbapenemases were detected in 9 patients [0.9% CI95 (0.397; 1.64)].
      Furthermore, antimicrobial susceptibility testing revealed 166 patients [16.0%
      CI95 (13.82; 18.38)] with extended-spectrum beta-lactamase (ESBL)-producing
      bacteria. At the time of investigation, K. pneumoniae producing the carbapenemase
      KPC-2 was diagnosed in 2 patients at one hospital. Moreover, it is necessary to
      remain vigilant towards other types of carbapenemase producers, as demonstrated
      by the finding of a Pseudomonas aeruginosa strain harbouring the carbapenemase
      VIM-1 in another hospital.

PMID- 24658671
TI  - [Healthcare associated infections (HAI), antibiotic use and prevalence of
      multidrug-resistant bacteria (MDRO) in residents of long-term care facilities:
      the Frankfurt HALT plus MDRO project 2012].
AB  - BACKGROUND: Residents of long-term care facilities (LTCF) are at risk of
      healthcare associated infections (HAI) and are often treated with antibiotics. In
      Germany a current HAI prevalence of 1.6 % and antibiotic use in 1.15% have been
      reported. However, data published on the current prevalence of multidrug
      resistant organisms (MRDO) in LTCFs in Germany are scarce. Therefore, the
      prevalence of HAI, antibiotic use and presence of MDROs were investigated in LTCF
      residents in Frankfurt am Main, Germany. METHODS: A point prevalence study of HAI
      and antibiotic use according to the European HALT protocol (health care
      associated infections in long-term care facilities) was carried out; swabs from
      the nose, throat and perineum were analyzed for methicillin-resistant
      Staphylococcus aureus (MRSA), extended spectrum beta-lactamase producing
      enterobacteria (ESBL) and vancomycin-resistant enterococci (VRE). RESULTS: A
      total of 880 residents in 8 LTCFs were enrolled in the study in 2012. The study
      participants were 30% male, 46.7%  were more than 85 years old, 70% exhibitied
      urinary or fecal incontinence, 11.4% had an indwelling urinary catheter and 0.1%
      a vascular catheter. Prevalence rates of HAI and of antibiotic use were 2.5 % and
      1.5%, respectively. The prevalence of MDROs in 184 residents who agreed to being
      tested for MDROs was 9.2% MRSA, 26.7% ESBL and 2.7% VRE. CONCLUSION: The HAIs and
      antibiotic use were comparable to the German HALT data from 2010. Compared to
      other German studies there is a steadily increasing MRSA problem in German LTCFs.
      High and increasing ESBL rates have been detected in German LTCFs. Further
      studies are needed to confirm this trend, preferably encompassing molecular
      methods to study epidemiology.

PMID- 24658672
TI  - [Results of the introduction of the "mre Netzwerk Nordwest" quality certification
      for nursing homes in Bonn].
AB  - BACKGROUND AND OBJECTIVES: The Commission for Hospital Hygiene and Infection
      Prevention of the Robert Koch Institute (KRINKO) published a Recommendation for
      Prevention of Infection in Nursing Homes in 2005 [Kommission fur
      Krankenhaushygiene und Infektionspravention beim Robert Koch-Institut (KRINKO)].
      The recommended measures for infection control of multidrug-resistant pathogens
      (MRP) are well known in most institutions. The "mre-Netzwerk Nordwest" quality
      certification is new, and was implemented by the KRINKO recommendation on a
      standardized basis for the first time in 2012 in Bonn, Germany. This study
      describes the first results of this initiative. MATERIAL AND METHODS: The
      certification contains guidelines based on the above-mentioned KRINKO
      recommendation and a survey on the status of infections and antibiotic therapies.
      Nursing homes in Bonn were asked to fulfill a list of ten criteria. The process
      was supervised by the local health authority and evaluated. RESULTS: Of 38
      nursing homes in Bonn, 19 acquired the certification. The survey showed that 1.4%
      of the residents were treated with antibiotics. Four pathogens were identified as
      MRP, but did not belong to the classic spectrum. In all, 42% of infections were
      treated with beta-lactams and 8% with quinolones. The evaluation showed that at
      least ten urinary tract catheters were removed because of the certification and a
      related re-evaluation of the indication was made by the treating physician.
      CONCLUSIONS: Implementation of the certification was assessed as positive,
      although it involves additional investments. The application of the approach was
      considered feasible as compared with other regions. The portion of antibiotic
      therapy use and partly that of other drugs was comparable to the findings of
      Wischnewski et al., Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
      54(11):1147-1152, 2011. Re-assessing the indication for urinary tract catheters
      might have a positive influence on the prevention of infections. The
      certification can trigger the exchange of information on MRP and antibiotic
      stewardship between nursing home physicians.

PMID- 24658673
TI  - [Widening health inequalities? Time trends concerning self-rated health, smoking
      and obesity between 1984/1985 and 1999/2000 among adults in Augsburg].
AB  - The analyses focused on time trends in health inequalities in the 25 to 64-year
      old population of Augsburg. The analyses are based on four independent cross
      sectional surveys from the MONICA/KORA study covering 15 years: 1984/1985 (n =
      4,022), 1989/1990 (n = 3,966), 1994/1995 (n = 3,916) and 1999/2000 (n = 3,492).
      Socioeconomic status (SES) was assessed by educational level and per capita
      household income with separate analyses for each of these two variables. Both
      absolute and relative health inequalities were calculated. The results showed
      that inequalities in self-rated health did not change very much (with some
      indications for increasing inequalities). However, concerning smoking the results
      clearly pointed towards increasing health inequalities (for example concerning
      relative inequalities among women by educational level: significant increase from
      survey to survey of about 20 %). The prevalence of obesity was increased in all
      SES groups but the inequalities did not change very much. These time trends show
      that the efforts aimed at reducing health inequalities should be intensified.

PMID- 24658674
TI  - [Health-related quality of life of overweight and obese adolescents: what
      differences can be seen by socio-economic status and education?].
AB  - In the present study the relation between overweight/obesity and health-related
      quality of life (HRQoL) in adolescence is analysed. Of special interest is the
      question, to what extent this relation varies by socio-economic status (SES) and
      education. Data base is a subsample of the German Health Interview and
      Examination Survey for Children and Adolescents (KiGGS, n = 6,813, 11-17 years).
      For the assessment of overweight and obesity, body mass index (BMI) was
      calculated based on standardised body height and weight measurements. The HRQoL
      was collected using the KINDL-R-questionnaire, which allows statements concerning
      a total rating as well as 6 dimensions: physical well-being, emotional well
      being, self-worth, family well-being, well-being in relation to friends/peers and
      school well-being. SES and education are analysed as moderating factors. The
      results show that obese boys as well as overweight and obese girls have a
      diminished HRQoL compared to normal weight peers. The analyses according to SES
      and education suggest that in girls this finding applies for all considered
      subgroups. Thus, in girls neither SES nor education has a moderating impact on
      the relation between overweight/obesity and HRQoL. In boys, only SES has a
      moderating impact on the relation between overweight and HRQoL in favour of the
      low status group. In terms of the relation between obesity and HRQoL, in boys
      also only SES has a moderating impact on the analysed relation, but here in
      favour of the high status group. Altogether, the results show that overweight and
      especially obese adolescents are affected in their HRQoL, this being almost
      independent of SES and education. Interventions to improve the HRQoL of
      overweight and obese adolescents should be independent of SES and education. 

PMID- 24658675
TI  - [Differences in sociodemographic characteristics, health, and health service use
      of children and adolescents according to their health insurance funds].
AB  - Differences in the socioeconomic characteristics and morbidity between members of
      German private and statutory health insurance funds and also between several
      statutory health insurances have been shown for adults. We used data from the
      National Health Survey for Children and Adolescents (KiGGS) to study differences
      in sociodemographic characteristics, health risks, morbidity, and health service
      use in child and adolescent insurants of different types of health insurance
      funds (Ersatzkasse, Allgemeine Ortskrankenkasse, Betriebskrankenkasse ,
      Innungskrankenkasse, other statutory health insurance funds, private health
      insurance). Differences in the proportion of respondents with a migration
      background, somatic diseases, psychopathological problems, and contact with a
      dentist between the different health insurance fund types were found. These
      results should be considered in studies on health inequalities, which often focus
      solely on differences between statutory and private health insurance. Our results
      are also of relevance for health services research using the claims data of
      health insurance funds.

PMID- 24658676
TI  - [Use of routine data from statutory health insurances for federal health
      monitoring purposes].
AB  - Federal health monitoring deals with the state of health and the health-related
      behavior of populations and is used to inform politics. To date, the routine data
      from statutory health insurances (SHI) have rarely been used for federal health
      monitoring purposes. SHI routine data enable analyses of disease frequency, risk
      factors, the course of the disease, the utilization of medical services, and
      mortality rates. The advantages offered by SHI routine data regarding federal
      health monitoring are the intersectoral perspective and the nearly complete
      absence of recall and selection bias in the respective population. Further, the
      large sample sizes and the continuous collection of the data allow reliable
      descriptions of the state of health of the insurants, even in cases of multiple
      stratification. These advantages have to be weighed against disadvantages linked
      to the claims nature of the data and the high administrative hurdles when
      requesting the use of SHI routine data. Particularly in view of the improved
      availability of data from all SHI insurants for research institutions in the
      context of the "health-care structure law", SHI routine data are an interesting
      data source for federal health monitoring purposes.

PMID- 24658678
TI  - The emergence of resistance to fungicides.
AB  - Many studies exist about the selection phase of fungicide resistance evolution,
      where a resistant strain is present in a pathogen population and is
      differentially selected for by the application of fungicides. The emergence phase
      of the evolution of fungicide resistance--where the resistant strain is not
      present in the population and has to arise through mutation and subsequently
      invade the population--has not been studied to date. Here, we derive a model
      which describes the emergence of resistance in pathogen populations of crops.
      There are several important examples where a single mutation, affecting binding
      of a fungicide with the target protein, shifts the sensitivity phenotype of the
      resistant strain to such an extent that it cannot be controlled effectively
      ('qualitative' or 'single-step' resistance). The model was parameterized for this
      scenario for Mycosphaerella graminicola on winter wheat and used to evaluate the
      effect of fungicide dose rate on the time to emergence of resistance for a range
      of mutation probabilities, fitness costs of resistance and sensitivity levels of
      the resistant strain. We also evaluated the usefulness of mixing two fungicides
      of differing modes of action for delaying the emergence of resistance. The
      results suggest that it is unlikely that a resistant strain will already have
      emerged when a fungicide with a new mode of action is introduced. Hence, 'anti
      emergence' strategies should be identified and implemented. For all simulated
      scenarios, the median emergence time of a resistant strain was affected little by
      changing the dose rate applied, within the range of doses typically used on
      commercial crops. Mixing a single-site acting fungicide with a multi-site acting
      fungicide delayed the emergence of resistance to the single-site component.
      Combining the findings with previous work on the selection phase will enable us
      to develop more efficient anti-resistance strategies.

PMID- 24658679
TI  - The crystal structure of Giardia duodenalis 14-3-3 in the apo form: when protein
      post-translational modifications make the difference.
AB  - The 14-3-3s are a family of dimeric evolutionary conserved pSer/pThr binding
      proteins that play a key role in multiple biological processes by interacting
      with a plethora of client proteins. Giardia duodenalis is a flagellated protozoan
      that affects millions of people worldwide causing an acute and chronic diarrheal
      disease. The single giardial 14-3-3 isoform (g14-3-3), unique in the 14-3-3
      family, needs the constitutive phosphorylation of Thr214 and the polyglycylation
      of its C-terminus to be fully functional in vivo. Alteration of the
      phosphorylation and polyglycylation status affects the parasite differentiation
      into the cyst stage. To further investigate the role of these post-translational
      modifications, the crystal structure of the g14-3-3 was solved in the unmodified
      apo form. Oligomers of g14-3-3 were observed due to domain swapping events at the
      protein C-terminus. The formation of filaments was supported by TEM. Mutational
      analysis, in combination with native PAGE and chemical cross-linking, proved that
      polyglycylation prevents oligomerization. In silico phosphorylation and molecular
      dynamics simulations supported a structural role for the phosphorylation of
      Thr214 in promoting target binding. Our findings highlight unique structural
      features of g14-3-3 opening novel perspectives on the evolutionary history of
      this protein family and envisaging the possibility to develop anti-giardial drugs
      targeting g14-3-3. 

PMID- 24658680
TI  - Early stage fetal neocortex exhibits a complex ganglioside profile as revealed by
      high resolution tandem mass spectrometry.
AB  - In this study we report on the first mass spectrometric (MS) investigation of
      gangliosides and preliminary assessment of the expression and structure in normal
      fetal neocortex in early developmental stages: 14th (Neo14) and 16th (Neo16)
      gestational weeks. Ganglioside analysis was carried out using a hybrid quadrupole
      time-of-flight (QTOF) MS with direct sample infusion by nanoelectrospray
      ionization (nanoESI) in the negative ion mode. Under optimized conditions a large
      number of glycoforms i.e. 75 in Neo14 and 71 in Neo16 mixtures were identified.
      The ganglioside species were found characterized by a high diversity of the
      ceramide constitution, an elevated sialylation degree (up to pentasialylated
      gangliosides-GP1) and sugar cores modified by fucosylation (Fuc) and acetylation
      (O-Ac). Direct comparison between Neo14 and Neo16 revealed a prominent expression
      of monosialylated structures in the Neo16 as well as the presence of a larger
      number of polysialylated species in Neo14 which constitutes a clear marker of
      rapid development-dependant changes in the sialylation. Also the MS screening
      results highlighted that presumably O-acetylation process occurs faster than
      fucosylation. CID MS/MS under variable collision energy applied for the first
      time for structural analysis of a fucosylated pentasialylated species induced an
      efficient fragmentation with generation of ions supporting Fuc-GP1d isomer in
      early stage fetal brain neocortex.

PMID- 24658681
TI  - Identification of glycosylated regions in pneumococcal PspA conjugated to
      serotype 6B capsular polysaccharide.
AB  - Conjugate vaccines are being widely used since their introduction. Nowadays the
      interest in these vaccines is still growing and new antigens and conjugate
      chemistry are being studied and developed. Pneumococcal surface protein A (PspA)
      is one of the most studied pneumococcal antigens and is an important vaccine
      candidate. One approach to broaden the conjugate vaccine coverage could be the
      conjugation of the polysaccharide to a pneumococcal protein such as PspA.
      Previous results have shown that conjugated recombinant fragment of PspA (rPspA)
      not only maintained but also in some conjugates improved the induction of
      protective antibodies raised against the protein carrier. We describe here a
      characterization study to identify the domains of Streptococcus pneumoniae
      recombinant PspA (rPspA), from family 1 clade 1 and family 2 clade 3, involved in
      the conjugation with serotype 6B capsular polysaccharide.

PMID- 24658682
TI  - Cardiac hybrid imaging.
AB  - Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging
      allows combined assessment of anatomical and functional aspects of cardiac
      disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows
      detection of coronary artery stenosis and myocardial perfusion abnormalities. The
      clinical value of hybrid imaging has been documented in several subsets of
      patients. In selected groups of patients, hybrid imaging improves the diagnostic
      accuracy to detect CAD compared to the single imaging techniques. Additionally,
      this approach facilitates functional interrogation of coronary stenoses and
      guidance with regard to revascularization procedures. Moreover, the anatomical
      information obtained from CT coronary angiography or coronary artery calcium
      scores (CACS) adds prognostic information over perfusion data from SPECT. The use
      of cardiac hybrid imaging has been favoured by the dissemination of dedicated
      hybrid systems and the release of dedicated image fusion software, which allow
      simple patient throughput for hybrid SPECT/CT studies. Further technological
      improvements such as more efficient detector technology to allow for low
      radiation protocols, ultra-fast image acquisition and improved low-noise image
      reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT
      in research and clinical practice.

PMID- 24658683
TI  - Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in
      patients with acute decompensated heart failure on treatment containing
      intravenous atrial natriuretic peptide.
AB  - PURPOSE: Aldosterone prevents the uptake of norepinephrine in the myocardium.
      Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin,
      inhibits aldosterone synthase gene expression in cultured cardiocytes. We
      evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity
      (CSNA) and aldosterone suppression in patients with acute decompensated heart
      failure (ADHF). METHODS: We studied 182 patients with moderate nonischemic ADHF
      requiring hospitalization and treated with standard therapy containing
      intravenous ANP and 10 age-matched normal control subjects. ANP was continuously
      infused for >96 h. In all subjects, delayed total defect score (TDS), heart to
      mediastinum ratio, and washout rate were determined by 123I
      metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic
      volume, end-systolic volume, and ejection fraction were determined by
      echocardiography. All patients with acute heart failure (AHF) were examined once
      within 3 days and then 4 weeks after admission, while the control subjects were
      examined only once (when their hemodynamics were normal). Moreover, for 62 AHF
      patients, plasma aldosterone concentrations were measured at admission and 1 h
      before stopping ANP infusion. RESULTS: 123I-MIBG scintigraphic and
      echocardiographic parameters in normal subjects were more favorable than those in
      patients with AHF (all p < 0.001). After treatment, all these parameters improved
      significantly in AHF patients (all p < 0.001). We also found significant
      correlation between percent changes of TDS and aldosterone concentrations (r =
      0.539, p < 0.001) in 62 AHF patients. CONCLUSION: The CSNA and LV performance
      were all improved in AHF patients. Furthermore, norepinephrine uptake of
      myocardium may be ameliorated by suppressing aldosterone production after
      standard treatment containing intravenous ANP.

PMID- 24658684
TI  - Widespread FRA1-dependent control of mesenchymal transdifferentiation programs in
      colorectal cancer cells.
AB  - Tumor invasion and metastasis involves complex remodeling of gene expression
      programs governing epithelial homeostasis. Mutational activation of the RAS-ERK
      is a frequent occurrence in many cancers and has been shown to drive
      overexpression of the AP-1 family transcription factor FRA1, a potent regulator
      of migration and invasion in a variety of tumor cell types. However, the nature
      of FRA1 transcriptional targets and the molecular pathways through which they
      promote tumor progression remain poorly understood. We found that FRA1 was
      strongly expressed in tumor cells at the invasive front of human colorectal
      cancers (CRCs), and that its depletion suppressed mesenchymal-like features in
      CRC cells in vitro. Genome-wide analysis of FRA1 chromatin occupancy and
      transcriptional regulation identified epithelial-mesenchymal transition (EMT)
      related genes as a major class of direct FRA1 targets in CRC cells. Expression of
      the pro-mesenchymal subset of these genes predicted adverse outcomes in CRC
      patients, and involved FRA-1-dependent regulation and cooperation with TGFbeta
      signaling pathway. Our findings reveal an unexpectedly widespread and direct role
      for FRA1 in control of epithelial-mesenchymal plasticity in CRC cells, and
      suggest that FRA1 plays an important role in mediating cross talk between
      oncogenic RAS-ERK and TGFbeta signaling networks during tumor progression. 

PMID- 24658685
TI  - A time- and matrix-dependent TGFBR3-JUND-KRT5 regulatory circuit in single breast
      epithelial cells and basal-like premalignancies.
AB  - Basal-like breast carcinoma is characterized by poor prognosis and high
      intratumour heterogeneity. In an immortalized basal-like breast epithelial cell
      line, we identified two anticorrelated gene-expression programs that arise among
      single extracellular matrix (ECM)-attached cells during organotypic three
      dimensional culture. The first contains multiple TGF-beta-related genes including
      TGFBR3, whereas the second contains JUND and the basal-like marker KRT5. TGFBR3
      and JUND interconnect through four negative-feedback loops to form a circuit that
      exhibits spontaneous damped oscillations in three-dimensional culture. The TGFBR3
      JUND circuit is conserved in some premalignant lesions that heterogeneously
      express KRT5. The circuit depends on ECM engagement, as detachment causes a
      rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine
      tenascin C, which is critical for intraductal colonization of basal-like breast
      cancer cells in vivo. Intratumour heterogeneity need not stem from partial
      differentiation and could instead reflect dynamic toggling of cells between
      expression states that are not cell autonomous. 

PMID- 24658688
TI  - Star shaped ferrocenyl truxenes: synthesis, structure and properties.
AB  - This article reports the design and synthesis of star shaped, C3-symmetric
      ferrocenyl substituted truxenes by the Pd-catalyzed Sonogashira cross-coupling
      and cycloaddition reaction. The single photon absorption and electrochemical
      properties indicate significant electronic interaction between ferrocene and
      truxene core. The bathochromic shift in the absorption spectra of truxenes 4a-4c
      and 5a is a function of enhanced conjugation. The incorporation of
      tetracyanoethylene (TCNE) results in a strong charge transfer band in truxene 5a.
      The single crystal structure of truxene 4a is presented, which shows interesting
      supramolecular interactions.

PMID- 24658686
TI  - The role of differential VE-cadherin dynamics in cell rearrangement during
      angiogenesis.
AB  - Endothelial cells show surprising cell rearrangement behaviour during angiogenic
      sprouting; however, the underlying mechanisms and functional importance remain
      unclear. By combining computational modelling with experimentation, we identify
      that Notch/VEGFR-regulated differential dynamics of VE-cadherin junctions drive
      functional endothelial cell rearrangements during sprouting. We propose that
      continual flux in Notch signalling levels in individual cells results in
      differential VE-cadherin turnover and junctional-cortex protrusions, which powers
      differential cell movement. In cultured endothelial cells, Notch signalling
      quantitatively reduced junctional VE-cadherin mobility. In simulations, only
      differential adhesion dynamics generated long-range position changes, required
      for tip cell competition and stalk cell intercalation. Simulation and
      quantitative image analysis on VE-cadherin junctional patterning in vivo
      identified that differential VE-cadherin mobility is lost under pathological high
      VEGF conditions, in retinopathy and tumour vessels. Our results provide a
      mechanistic concept for how cells rearrange during normal sprouting and how
      rearrangement switches to generate abnormal vessels in pathologies. 

PMID- 24658687
TI  - Metabolic control of YAP and TAZ by the mevalonate pathway.
AB  - The YAP and TAZ mediators of the Hippo pathway (hereafter called YAP/TAZ) promote
      tissue proliferation and organ growth. However, how their biological properties
      intersect with cellular metabolism remains unexplained. Here, we show that
      YAP/TAZ activity is controlled by the SREBP/mevalonate pathway. Inhibition of the
      rate-limiting enzyme of this pathway (HMG-CoA reductase) by statins opposes
      YAP/TAZ nuclear localization and transcriptional responses. Mechanistically, the
      geranylgeranyl pyrophosphate produced by the mevalonate cascade is required for
      activation of Rho GTPases that, in turn, activate YAP/TAZ by inhibiting their
      phosphorylation and promoting their nuclear accumulation. The mevalonate-YAP/TAZ
      axis is required for proliferation and self-renewal of breast cancer cells. In
      Drosophila melanogaster, inhibition of mevalonate biosynthesis and
      geranylgeranylation blunts the eye overgrowth induced by Yorkie, the YAP/TAZ
      orthologue. In tumour cells, YAP/TAZ activation is promoted by increased levels
      of mevalonic acid produced by SREBP transcriptional activity, which is induced by
      its oncogenic cofactor mutant p53. These findings reveal an additional layer of
      YAP/TAZ regulation by metabolic cues. 

PMID- 24658689
TI  - The View of Religious Officials on Organ Donation and Transplantation in the
      Zeytinburnu District of Istanbul.
AB  - One of the obstacles to organ donation and transplantation in Turkey is that of
      religious beliefs and, at this point, religious officials constitute a key aspect
      of this problem. Positive or negative viewpoints held by religious officials
      regarding organ donation and transplantation are influential in guiding the
      public. This descriptive study was conducted for the purpose of describing
      religious officials' viewpoints on this subject. To determine the opinions of 40
      religious officials from among the imams and muezzins working in Zeytinburnu
      District Mufti (Religious Officials Superior) Station who participated in a
      normal meeting in April and who fully completed the survey. A 27-question survey
      form was used that consisted of open-ended and closed questions, 5 of which were
      on socio-demographic characteristics, 13 on viewpoints on organ donation and
      transplantation, and 9 on the Islamic viewpoint regarding organ donation and
      transplantation. For the analysis of the results, Student's t test and one-way
      ANOVA tests were used. It was found that all of the religious officials believed
      in the importance of organ donation, 80 % considered donating their organs, and 5
      % had made an organ donation. Of the religious officials who had not donated
      organs, 35 % gave an answer that there was no specific reason and 27.5 % stated
      that they had never considered the subject. While the number of those stating
      that they would donate the organs of a close associate who had died, 77.5 % of
      them who did not want to donate gave as their reason the idea that if it were
      him, he would perhaps not want to give his organs after death. Of the religious
      officials questioned, 92.5 % asserted that the religion of Islam looked
      positively on organ donation and transplantation, 55 % stated that the knowledge
      of religious officials in the country was inadequate regarding this subject, and
      65 % said that for interest in organ donation to increase, religious officials
      should make speeches and raise the issue with the public in conversations,
      meetings, and sermons. Fully 85 % asserted that for interest in organ donation in
      Turkey to increase, religious officials have to lead on the subject. Of those
      questioned, 52.5 % considered their knowledge on organ donation and
      transplantation to be adequate and that they had obtained 52.5 % of such
      information from seminars/conferences, 50 % from television/radio, and 45 % from
      Directorate of Religious Affairs publications. However, 40 % expressed that they
      did not know where organ donations were made. One reason for inadequate organ
      donation in Turkey is that of incorrect religious beliefs. Thus, it is necessary
      that informative efforts are made by the Directorate of Religious Affairs through
      in-house training programs, and that healthcare, religious, and legal officials
      work jointly to inform the public about organ donation, organ transplantation,
      and brain death. Additionally, religious officials should donate organs by the
      way of example and, to increase their sensitivity, healthcare professionals
      should go more frequently to mosques and Mufti Stations.

PMID- 24658690
TI  - Highlights from the scientific and educational abstracts presented at the ASER
      2013 Annual Scientific Meeting and Postgraduate Course.
AB  - The American Society of Emergency Radiology (ASER) 2013 Annual Scientific Meeting
      and Postgraduate Course offered dedicated learning sessions, oral presentations,
      and digital exhibits on a broad spectrum of topics in emergency radiology,
      including traumatic and nontraumatic emergencies, quality, communication,
      education, and technology. This article highlights the scientific and educational
      abstracts presented at the meeting.

PMID- 24658692
TI  - Repeated upper endoscopy in the Medicare population: a retrospective analysis.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) is done often for various
      indications. Little is known about the frequency of repeated EGD and the
      diagnoses that drive it. OBJECTIVE: To describe the frequency of repeated EGD in
      the Medicare population and determine diagnoses most often associated with it.
      DESIGN: Retrospective analysis. SETTING: Medicare database. PATIENTS: Among a 5%
      random sample of Medicare beneficiaries, Current Procedural Terminology (CPT)
      codes were used to identify patients who had an index EGD between 2004 and 2006.
      Diagnoses from the International Classification of Diseases, Ninth Revision,
      Clinical Modification, reported for the index endoscopy were divided into 3
      diagnostic groups on the basis of whether the index diagnosis suggested that
      repeated EGD was expected, uncertain, or not expected. MEASUREMENTS: Proportion
      of patients with repeated EGD within 3 years of an index EGD. RESULTS:
      Approximately 12% of Medicare beneficiaries had an EGD between 2004 and 2006 (n =
      108 785). Of these, 33% (n = 36 331) had at least 1 repeated EGD within 3 years.
      Of all patients with initial EGDs, 10% (n = 11 370) had an associated diagnosis
      suggesting a need for follow-up examination, whereas 61% (n = 66 307) did not. Of
      all patients with repeated examinations, 54% (n = 19 687) came from the group in
      which repeated EGD was not expected. When new clinical events were excluded, 43%
      of all patients with repeated EGDs (n = 15 706) did not have a diagnosis at index
      or repeated EGD that justified a repeated examination. LIMITATION: Whether
      individual procedures were clinically indicated cannot be verified. CONCLUSION:
      One in 3 Medicare beneficiaries who received an EGD had a repeated EGD within 3
      years. Nearly one half of repeated examinations were done in patients with
      diagnoses at index or repeated EGD that did not suggest the need for a repeated
      examination. PRIMARY FUNDING SOURCE: None.

PMID- 24658691
TI  - Aggregate cost of mammography screening in the United States: comparison of
      current practice and advocated guidelines.
AB  - BACKGROUND: Controversy exists over how often and at what age mammography
      screening should be implemented. Given that evidence supports less frequent
      screening, the cost differences among advocated screening policies should be
      better understood. OBJECTIVE: To estimate the aggregate cost of mammography
      screening in the United States in 2010 and compare the costs of policy
      recommendations by professional organizations. DESIGN: A model was developed to
      estimate the cost of mammography screening in 2010 and 3 screening strategies:
      annual (ages 40 to 84 years), biennial (ages 50 to 69 years), and U.S. Preventive
      Services Task Force (USPSTF) guidelines (biennial for those aged 50 to 74 years
      and personalized based on risk for those younger than 50 years and based on
      comorbid conditions for those 75 years and older). SETTING: United States.
      PATIENTS: Women aged 40 to 85 years. INTERVENTION: Mammography annually,
      biennially, or following USPSTF guidelines. MEASUREMENTS: Cost of screening per
      year, using Medicare reimbursements. RESULTS: The estimated cost of mammography
      screening in the United States in 2010 was $7.8 billion, with approximately 70%
      of women screened. The simulated cost of screening 85% of women was $10.1
      billion, $2.6 billion, and $3.5 billion for annual, biennial, and USPSTF
      guidelines, respectively. The largest drivers of cost (in order) were screening
      frequency, percentage of women screened, cost of mammography, percentage of women
      screened with digital mammography, and percentage of mammography recalls.
      LIMITATION: Cost estimates and assumptions used in the model were conservative.
      CONCLUSION: The cost of mammography varies by at least $8 billion per year on the
      basis of screening strategy. The USPSTF guidelines are based on the scientific
      evidence to date to maximize patient benefit and minimize harm but also result in
      far more effective use of resources. PRIMARY FUNDING SOURCE: University of
      California and the Safeway Foundation.

PMID- 24658693
TI  - U.S. physicians' perspective of adult vaccine delivery.
AB  - BACKGROUND: Adults are at substantial risk for vaccine-preventable disease, but
      their vaccination rates remain low. OBJECTIVE: To assess practices for assessing
      vaccination status and stocking recommended vaccines, barriers to vaccination,
      characteristics associated with reporting financial barriers to delivering
      vaccines, and practices regarding vaccination by alternate vaccinators. DESIGN:
      Mail and Internet-based survey. SETTING: Survey conducted from March to June
      2012. PARTICIPANTS: General internists and family physicians throughout the
      United States. MEASUREMENTS: A financial barriers scale was created.
      Multivariable linear modeling for each specialty was performed to assess
      associations between a financial barrier score and physician and practice
      characteristics. RESULTS: Response rates were 79% (352 of 443) for general
      internists and 62% (255 of 409) for family physicians. Twenty-nine percent of
      general internists and 32% of family physicians reported assessing vaccination
      status at every visit. A minority used immunization information systems (8% and
      36%, respectively). Almost all respondents reported assessing need for and
      stocking seasonal influenza; pneumococcal; tetanus and diphtheria; and tetanus,
      diphtheria, and acellular pertussis vaccines. However, fewer assessed and stocked
      other recommended vaccines. The most commonly reported barriers were financial.
      Characteristics significantly associated with reporting greater financial
      barriers included private practice setting, fewer than 5 providers in the
      practice, and, for general internists only, having more patients with Medicare
      Part D. The most commonly reported reasons for referring patients elsewhere
      included lack of insurance coverage for the vaccine (55% for general internists
      and 62% for family physicians) or inadequate reimbursement (36% and 41%,
      respectively). Patients were most often referred to pharmacies/retail stores and
      public health departments. LIMITATIONS: Surveyed physicians may not be
      representative of all physicians. CONCLUSION: Improving adult vaccination
      delivery will require increased use of evidence-based methods for vaccination
      delivery and concerted efforts to resolve financial barriers, especially for
      smaller practices and for general internists who see more patients with Medicare
      Part D. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

PMID- 24658695
TI  - Advisory committee on immunization practices recommended immunization schedule
      for adults aged 19 years or older: United States, 2014.

PMID- 24658694
TI  - Accuracy of fecal immunochemical tests for colorectal cancer: systematic review
      and meta-analysis.
AB  - BACKGROUND: Performance characteristics of fecal immunochemical tests (FITs) to
      screen for colorectal cancer (CRC) have been inconsistent. PURPOSE: To synthesize
      data about the diagnostic accuracy of FITs for CRC and identify factors affecting
      its performance characteristics. DATA SOURCES: Online databases, including
      MEDLINE and EMBASE, and bibliographies of included studies from 1996 to 2013.
      STUDY SELECTION: All studies evaluating the diagnostic accuracy of FITs for CRC
      in asymptomatic, average-risk adults. DATA EXTRACTION: Two reviewers
      independently extracted data and critiqued study quality. DATA SYNTHESIS:
      Nineteen eligible studies were included and meta-analyzed. The pooled
      sensitivity, specificity, positive likelihood ratio, and negative likelihood
      ratio of FITs for CRC were 0.79 (95% CI, 0.69 to 0.86), 0.94 (CI, 0.92 to 0.95),
      13.10 (CI, 10.49 to 16.35), 0.23 (CI, 0.15 to 0.33), respectively, with an
      overall diagnostic accuracy of 95% (CI, 93% to 97%). There was substantial
      heterogeneity between studies in both the pooled sensitivity and specificity
      estimates. Stratifying by cutoff value for a positive test result or removal of
      discontinued FIT brands resulted in homogeneous sensitivity estimates.
      Sensitivity for CRC improved with lower assay cutoff values for a positive test
      result (for example, 0.89 [CI, 0.80 to 0.95] at a cutoff value less than 20 ug/g
      vs. 0.70 [CI, 0.55 to 0.81] at cutoff values of 20 to 50 ug/g) but with a
      corresponding decrease in specificity. A single-sample FIT had similar
      sensitivity and specificity as several samples, independent of FIT brand.
      LIMITATIONS: Only English-language articles were included. Lack of data prevented
      complete subgroup analyses by FIT brand. CONCLUSION: Fecal immunochemical tests
      are moderately sensitive, are highly specific, and have high overall diagnostic
      accuracy for detecting CRC. Diagnostic performance of FITs depends on the cutoff
      value for a positive test result. PRIMARY FUNDING SOURCE: National Institute of
      Diabetes and Digestive and Kidney Diseases and National Cancer Institute.

PMID- 24658696
TI  - When frail elderly adults get sick: alternatives to hospitalization.

PMID- 24658697
TI  - The cost of breast cancer screening in the United States: a picture is worth ...
      a billion dollars?

PMID- 24658698
TI  - "Rightsizing" use of upper endoscopy.

PMID- 24658699
TI  - The seductress.

PMID- 24658700
TI  - Screening for lung cancer with low-dose computed tomography.

PMID- 24658701
TI  - In the Clinic. Concussion.

PMID- 24658702
TI  - Endogenously imprinted genes in Drosophila melanogaster.
AB  - Genomic imprinting is an epigenetic state that results from differential
      processing of chromosomes during gametogenesis and which can cause differential
      expression of genes depending on the sex of the parent transmitting that gene. In
      Drosophila, many examples of imprinted marker genes have been documented and
      imprinting of these genes involves highly conserved epigenetic regulators.
      However, no endogenously imprinted genes have yet been identified. Here we
      present a phenotypic and transcriptional analysis of parthenogenetic
      (gynogenetic) and genotypically identical but sexually produced adult female
      Drosophila. We find that while parthenogenetic females have a superficially
      normal phenotype and are viable and fertile, their lifespan is extended relative
      to their sexually-produced counterparts. Microarray/transcriptional analysis of
      parthenogenetic versus sexually-produced females reveals 76 genes with
      consistently altered patterns of expression, 36 upregulated and 40 downregulated,
      some with known effects on aging. Analysis of individuals with uniparental
      inheritance of only portions of their genome suggest that many of these genes may
      be indirectly imprinted, responding to either other imprinted genes or
      redistribution of chromatin components that are differentially allocated to sex
      and autosomal heterochromatin in a sex-dependent manner during gametogenesis. As
      gene expression dependent on the parental origin of the genome meets the
      definition of genomic imprinting, our study provides evidence that endogenous
      genes are imprinted in Drosophila.

PMID- 24658704
TI  - A computer simulation of the networked structure of a hydrogel prepared from a
      tetra-armed star pre-polymer.
AB  - We used a coarse-grained (CG) molecular dynamics model with potentials
      convertible to actual units to simulate the polymerization of a gel of a tetra
      armed poly(ethylene glycol) derivative (MW ~ 6000) under aqueous conditions and
      analysed its three-dimensional network structure. The radius of gyration of
      individual pre-polymers after gelation was slightly increased compared with that
      of the single pre-polymer before gelation, and its distribution was broad,
      attributable to inter- and intra-molecular bonds. The largest pores in the unit
      cell were about 3.5-3.9 nm. The existence of large pores seems to explain the
      protein encapsulation capability of and protein leakage from the gel indicating
      that the CG simulation, which maintains information about potentials in actual
      units, is an effective tool for investigating gel properties that are difficult
      to measure in real experiments. 

PMID- 24658703
TI  - Brown fat determination and development from muscle precursor cells by novel
      action of bone morphogenetic protein 6.
AB  - Brown adipose tissue (BAT) plays a pivotal role in promoting energy expenditure
      by the virtue of uncoupling protein-1 (UCP-1) that differentiates BAT from its
      energy storing white adipose tissue (WAT) counterpart. The clinical implication
      of "classical" BAT (originates from Myf5 positive myoblastic lineage) or the
      "beige" fat (originates through trans-differentiation of WAT) activation in
      improving metabolic parameters is now becoming apparent. However, the inducers
      and endogenous molecular determinants that govern the lineage commitment and
      differentiation of classical BAT remain obscure. We report here that in the
      absence of any forced gene expression, stimulation with bone morphogenetic
      protein 6 (BMP6) induces brown fat differentiation from skeletal muscle precursor
      cells of murine and human origins. Through a comprehensive transcriptional
      profiling approach, we have discovered that two days of BMP6 stimulation in C2C12
      myoblast cells is sufficient to induce genes characteristic of brown
      preadipocytes. This developmental switch is modulated in part by newly identified
      regulators, Optineurin (Optn) and Cyclooxygenase-2 (Cox2). Furthermore, pathway
      analyses using the Causal Reasoning Engine (CRE) identified additional potential
      causal drivers of this BMP6 induced commitment switch. Subsequent analyses to
      decipher key pathway that facilitates terminal differentiation of these BMP6
      primed cells identified a key role for Insulin Like Growth Factor-1 Receptor (IGF
      1R). Collectively these data highlight a therapeutically innovative role for BMP6
      by providing a means to enhance the amount of myogenic lineage derived brown fat.

PMID- 24658706
TI  - Work-related musculoskeletal disorders among sugarcane farmers in north-eastern
      Thailand.
AB  - This cross-sectional analytical study aimed to identify prevalence and factors
      associated with work-related musculoskeletal disorders (WMSDs) among sugarcane
      farmers. Cluster random sampling was used to select 540 sugarcane farmers from 3
      provinces in North-Eastern Thailand. Three related questionnaires, plus
      assessments by 2 expert physiotherapists, were used to check for factors
      associated with WMSDs and prevalence of WMSDs. Data were analyzed using
      descriptive statistics and multiple logistic regressions. The results indicated
      the prevalence of WMSDs among sugarcane farmers in the 7 days before the
      interview and looking back over the previous 12 months were 82.96% and 88.70%,
      respectively. Factors significantly associated with reporting WMSDs (P value <
      .05) during past 12 months were (a) repetitive motions (adjusted odds ratio [OR]
      = 1.90; 95% confidence interval [CI] = 1.05-3.43), (b) working in awkward
      postures (adjusted OR = 1.95; 95% CI = 1.01-3.77), (c) forceful exertions
      (adjusted OR = 2.78; 95% CI = 1.54-5.02), and (d) stress about future income
      (adjusted OR = 1.80; 95% CI = 1.02-3.16). Recommendations are made for risk
      prevention strategies. 

PMID- 24658705
TI  - Additional weight load increases freezing of gait episodes in Parkinson's
      disease; an experimental study.
AB  - Freezing of gait is an episodic gait disorder,characterized by the inability to
      generate effective forward stepping movements. The pathophysiology underlying
      freezing of gait remains insufficiently understood, and this hampers the
      development of better treatment strategies.Preliminary evidence suggests that
      impaired force control during walking may contribute to freezing episodes, with
      difficulty to unload the swing leg and initiate the swing phase. Here, we used
      external loading to manipulate force control and to investigate its influence on
      freezing of gait.Twelve Parkinson's disease patients with freezing of gait
      performed three contrasting tasks: (1) loaded gait while wearing a belt fortified
      with lead weights; (2) weight supported gait using a parachute harness connected
      to a rigid metal cable running above the gait trajectory; and (3)normal gait.
      Gait tasks were used to provoke freezing episodes, including rapid 360 degrees 
      turns. Freezing episodes were quantified using blinded, videotaped clinical
      assessment. Furthermore, ground reaction forces and body kinematics were
      recorded. Loading significantly increased the mean number of freezing episodes
      per trial compared to the normal gait condition (P<0.05), but the effect of
      weight support was not consistent. Loading particularly increased the number of
      freezing episodes during rapid short steps. Step length was significantly smaller
      during loaded gait compared to normal gait (P<0.05), but changes in anticipatory
      postural adjustments were not different.Our results may point to impaired force
      control playing a key role in freezing of gait. Future studies should further
      investigate the mechanism, i.e., the contribution of deficient load feedback, and
      evaluate which forms of weight support might offer treatment opportunities.

PMID- 24658707
TI  - Comparison of low molecular weight hydroxyethyl starch and human albumin as
      priming solutions in children undergoing cardiac surgery.
AB  - Human albumin is the conventional cardiopulmonary bypass circuit primer. However,
      it has high manufacturing costs. Crystalloid and colloid solutions have been
      developed as alternatives, including a new generation of non-ionic hydroxyethyl
      starch (HES). The efficacy of hydroxyethyl starch with a 130 molecular weight and
      substitution degree of 0.4 (hydroxyethyl starch 130/0.4) was compared with human
      albumin for use in cardiopulmonary bypass surgery in American Society of
      Anesthesiologists' grade I-II pediatric congenital heart disease patients.
      Efficacy was evaluated by comparing perioperative hemodynamic parameters,
      including plasma colloid osmotic pressure, renal function, blood loss, allogeneic
      blood volumes and plasma volume substitution. The hydroxyethyl starch group
      exhibited significantly higher preoperative colloid osmotic pressure (p<0.01) and
      significantly lower operative renal function and postoperative allogeneic blood
      volumes than the human albumin group. No significant differences were observed in
      serum creatinine, glucose, hematocrit or lactic acid levels (p>0.05). Our results
      indicate that hydroxyethyl starch may be a viable alternative to human albumin in
      pediatric patients undergoing relatively simple cardiopulmonary bypass surgeries.

PMID- 24658708
TI  - The influence on sarcopenia of muscle quality and quantity derived from magnetic
      resonance imaging and neuromuscular properties.
AB  - The relative contributions of intrinsic and extrinsic neuromuscular factors on
      sarcopenia are poorly understood. The associations among age-related declines of
      strength, muscle mass, and muscle quality in response to motor unit (MU) loss
      have not been systematically investigated in the same groups of subjects. The
      purpose was to assess MU loss, MRI-derived muscle cross-sectional area (CSA),
      muscle protein quantity (MPQ), and normalized strength of the dorsiflexors in one
      group of young (~25 years) adult males compared with two groups of healthy men
      aged 60-85 years. Muscle strength was assessed on a dynamometer and was ~25 %
      lower in both older groups, but CSA was less only in the older (>75 years) men,
      with no differences between the young and old (60-73 years). Normalized strength
      tended to be lower in both groups of aged men compared to young. For MPQ, only
      the older men showed ~8 % lower values than the young and old men. Older men had
      fewer functioning MUs than old, and both groups of aged men had fewer MUs than
      young men. Muscle quality appears to be maintained in the old likely due to
      compensatory MU remodeling, but in the older group (>75 years), MU loss was
      higher and MPQ was lower.

PMID- 24658710
TI  - Epidemiological survey of ossification of the posterior longitudinal ligament in
      an adult Korean population: three-dimensional computed tomographic observation of
      3,240 cases.
AB  - The prevalence rates of ossification of the posterior longitudinal ligament
      (OPLL) in the Korean population were reported as 3.4 and 0.6%. However, these
      studies were performed before the era of three-dimensional computed tomography
      (3D CT). We investigated the prevalence of cervical OPLL on the basis of 3D CT
      and features of OPLL distribution in an adult Korean population. During 2011 and
      2012, a total of 3,240 patients were enrolled who had undergone thyroid 3D CT. A
      total of 1,084 men and 2,156 women were included. Axial and sagittal
      reconstruction images were used for observations. More than 2 mm thickness in an
      axial image was the criterion for the presence of OPLL. The prevalence rate was
      adjusted according to a standardized population according to Statistics Korea.
      The OPLL prevalence rate was 5.7%. The standardized prevalence rate was 4.60%.
      The standardized prevalence rates in men and women were 6.43 and 3.61%,
      respectively. The over-70 age group had the highest OPLL prevalence. Age and
      prevalence rate were positively correlated in men and women (correlation
      coefficient 0.991 and 0.991, P<0.001 and P<0.0001, respectively). Among OPLL
      types, the multiple segmental type was most frequent (37.3%). The most commonly
      involved level was C5 (4.8% in men, 2.2% in women), C4 (4.6% in men, 1.2% in
      women), and C6 (3.7% in men, 2.4% in women) segments, in decreasing order. To our
      knowledge, this study is the first 3D CT-based epidemiologic study on cervical
      OPLL in a Korean population.

PMID- 24658711
TI  - A new realization of time-to-digital converters based on FPGA internal routing
      resources.
AB  - Time-to-digital converters (TDC) implemented in a single field-programmable gate
      array (FPGA) chip which overcome the difficulties found in other FPGA-based TDCs
      are proposed in this paper. Emphasis is placed on the construction of two delay
      lines with a good delay consistency, as well as a minimum delay difference by
      which the measurement resolution can be improved and measurement error can be
      reduced. A modified vernier delay line structure is introduced which abandoned
      special delay elements and directly used FPGA internal routing resources to
      generate the cell delay. To get a good consistency for the system, manual
      placement and manual routing are used to standardize the delays. The resolution
      of the system is 9 ps and the standard deviation is less than 1 least significant
      bit (LSB) within the whole measurement range. The corrected differential
      nonlinearity is as low as 0.11 LSB. Experiments showed that the proposed system
      features high accuracy, low cost, and high stability. 

PMID- 24658709
TI  - Synchronization during an internally directed cognitive state in healthy aging
      and mild cognitive impairment: a MEG study.
AB  - Mild cognitive impairment (MCI) is a stage between healthy aging and dementia. It
      is known that in this condition the connectivity patterns are altered in the
      resting state and during cognitive tasks, where an extra effort seems to be
      necessary to overcome cognitive decline. We aimed to determine the functional
      connectivity pattern required to deal with an internally directed cognitive state
      (IDICS) in healthy aging and MCI. This task differs from the most commonly
      employed ones in neurophysiology, since inhibition from external stimuli is
      needed, allowing the study of this control mechanism. To this end,
      magnetoencephalographic (MEG) signals were acquired from 32 healthy individuals
      and 38 MCI patients, both in resting state and while performing a subtraction
      task of two levels of difficulty. Functional connectivity was assessed with phase
      locking value (PLV) in five frequency bands. Compared to controls, MCIs showed
      higher PLV values in delta, theta, and gamma bands and an opposite pattern in
      alpha, beta, and gamma bands in resting state. These changes were associated with
      poorer neuropsychological performance. During the task, this group exhibited a
      hypersynchronization in delta, theta, beta, and gamma bands, which was also
      related to a lower cognitive performance, suggesting an abnormal functioning in
      this group. Contrary to controls, MCIs presented a lack of synchronization in the
      alpha band which may denote an inhibition deficit. Additionally, the magnitude of
      connectivity changes rose with the task difficulty in controls but not in MCIs,
      in line with the compensation-related utilization of neural circuits hypothesis
      (CRUNCH) model.

PMID- 24658712
TI  - State-of-the-art RF signal generation from optical frequency division.
AB  - We present the design of a novel, ultralow-phase-noise frequency synthesizer
      implemented with extremely-low-noise regenerative frequency dividers. This
      synthesizer generates eight outputs, viz. 1.6 GHz, 320 MHz, 160 MHz, 80 MHz, 40
      MHz, 20 MHz, 10 MHz and 5 MHz for an 8 GHz input frequency. The residual single
      sideband (SSB) phase noises of the synthesizer at 5 and 10 MHz outputs at 1 Hz
      offset from the carrier are -150 and -145 dBc/Hz, respectively, which are
      unprecedented phase noise levels. We also report the lowest values of phase noise
      to date for 5 and 10 MHz RF signals achieved with our synthesizer by dividing an
      8 GHz signal generated from an ultra-stable optical-comb-based frequency
      division. The absolute SSB phase noises achieved for 5 and 10 MHz signals at 1 Hz
      offset are -150 and -143 dBc/Hz, respectively; at 100 kHz offset, they are -177
      and -174 dBc/Hz, respectively. The phase noise of the 5 MHz signal corresponds to
      a frequency stability of approximately 7.6 * 10(-15) at 1 s averaging time for a
      measurement bandwidth (BW) of 500 Hz, and the integrated timing jitter over 100
      kHz BW is 20 fs.

PMID- 24658713
TI  - Multipoint dissemination of RF frequency in fiber optic link with stabilized
      propagation delay.
AB  - In this paper, we present the concept of accessing the signal at some midpoint of
      a frequency dissemination system with stabilized propagation delay, which allows
      building the point-to-multipoint frequency dissemination network. In the first
      experiments with a 160 km-long fiber link composed of a field-deployed optical
      cable and fibers spooled in the lab, exposed to both diurnal and seasonal
      temperature variations, in the access node, we obtained the Allan deviation of a
      10- MHz frequency signal of about 3 * 10(-17) and the time deviation not greater
      than 2 ps for 10(5) s averaging.

PMID- 24658714
TI  - Role of intracellular calcium and reactive oxygen species in microbubble-mediated
      alterations of endothelial layer permeability.
AB  - Drugs will be delivered to diseased tissue more efficiently if the vascular
      endothelial permeability is increased. Ultrasound in combination with an
      ultrasound contrast agent is known to increase the permeability of the
      endothelial layer, but the mechanism is not known. The goal of this study was to
      elucidate whether intracellular calcium ions, [Ca(2+)]i, and reactive oxygen
      species (ROS) are part of the mechanism that leads to an increased endothelial
      layer permeability following ultrasound and microbubble treatment. Human
      umbilical vein endothelial cells (HUVECs) treated for 2 min with ultrasound
      activated microbubbles (1 MHz, 210 kPa, 10 000 cycles, 20 Hz repetition rate) had
      an increased permeability that lasted up to 12 h. Recovery of permeability after
      2 h was only found when HUVECs were preincubated with the [Ca(2+)]i chelator
      BAPTA-AM or the antioxidant butylated hydroxytoluene (BHT). This suggests that
      both [Ca(2+)]i and ROS play an important role in the mechanism of increased
      permeability following ultrasound in combination with microbubble treatment.

PMID- 24658715
TI  - Synthetic aperture focusing for short-lag spatial coherence imaging.
AB  - It has been demonstrated that short-lag spatial coherence (SLSC) ultrasound
      imaging can provide improved speckle SNR and lesion CNR compared with
      conventional Bmode images, especially in the presence of noise and clutter.
      Application of the van Cittert-Zernike theorem predicts that coherence among the
      ultrasound echoes received across an array is reduced significantly away from the
      transmit focal depth, leading to a limited axial depth of field in SLSC images.
      Transmit focus throughout the field of view can be achieved using synthetic
      aperture methods to combine multiple transmit events into a single final image. A
      synthetic aperture can be formed with either focused or diverging transmit beams.
      We explore the application of these methods to form synthetically focused channel
      data to create SLSC images with an extended axial depth of field. An analytical
      expression of SLSC image brightness through depth is derived for the dynamic
      receive focus case. Experimental results in a phantom and in vivo are presented
      and compared with dynamic receive focused SLSC images, demonstrating improved SNR
      and CNR away from the transmit focus and an axial depth of field four to five
      times longer. 

PMID- 24658716
TI  - A study of the adult zebrafish ventricular function by retrospective Doppler
      gated ultrahigh-frame-rate echocardiography.
AB  - The zebrafish (Danio rerio) has become a preferred animal model for studying
      various human diseases, particularly those related to cardiovascular
      regeneration; therefore, a noninvasive imaging modality is needed for observing
      the cardiac function of zebrafish. Because of its high resolution, high-frequency
      ultrasound B-mode imaging has recently been used successfully to observe the
      heart of adult zebrafish. However, ultrahigh-frame-rate echocardiography
      combining Bmode imaging and color flow imaging is still needed to observe the
      detailed transient motions of the zebrafish ventricle. This study develops an 80
      MHz ultrahigh-frame-rate echocardiography system for this purpose, based on
      retrospective Doppler- gated technology. B-mode and color flow images of the
      cardiovascular system of the zebrafish were reconstructed by two-dimensional
      autocorrelation at maximum frame rates of up to 40,000 and 400 fps, respectively.
      The timings of end diastole (E(D)) and end systole (E(S)) of ventricle can be
      determined by using this high-resolution image system. Two ventricular function
      parameters-fractional shortening (FS) and fractional area change (FAC)-were
      measured for evaluating the ventricular function by using E(D) and E(S) with
      their corresponding ventricular dimensions. The experimental results indicated
      that the measured FS values were 42 +/- 4% (mean +/- standard deviation) and 60
      +/- 13% for the long axis and short axis of the ventricle, respectively, and that
      FAC was 77 +/- 9%. This is the first report of these ventricular function
      parameters for a normal adult zebrafish. The results showed that retrospective
      high-frequency echocardiography is a useful tool for studying the cardiac
      function of normal adult zebrafish.

PMID- 24658717
TI  - SARUS: A Synthetic Aperture Real-time Ultrasound System.
AB  - The Synthetic Aperture Real-time Ultrasound System (SARUS) for acquiring and
      processing synthetic aperture (SA) data for research purposes is described. The
      specifications and design of the system are detailed, along with its performance
      for SA, nonlinear, and 3-D flow estimation imaging. SARUS acquires individual
      channel data simultaneously for up to 1024 transducer elements for a couple of
      heart beats, and is capable of transmitting any kind of excitation. The 64 boards
      in the system house 16 transmit and 16 receive channels each, where sampled
      channel data can be stored in 2 GB of RAM and processed using five field
      programmable gate arrays (FPGAs). The fully parametric focusing unit calculates
      delays and apodization values in real time in 3-D space and can produce 350
      million complex samples per channel per second for full non-recursive synthetic
      aperture B-mode imaging at roughly 30 high-resolution images/s. Both RF element
      data and beamformed data can be stored in the system for later storage and
      processing. The stored data can be transferred in parallel using the system's
      sixty-four 1-Gbit Ethernet interfaces at a theoretical rate of 3.2 GB/s to a 144
      core Linux cluster.

PMID- 24658718
TI  - Design and evaluation of a transesophageal HIFU probe for ultrasound-guided
      cardiac ablation: simulation of a HIFU mini-maze procedure and preliminary ex
      vivo trials.
AB  - Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Left atrial
      catheter ablation is currently performed to treat this disease. Several energy
      sources are used, such as radio-frequency or cryotherapy. The main target of this
      procedure is to isolate the pulmonary veins. However, significant complications
      caused by the invasive procedure are described, such as stroke, tamponade, and
      atrioesophageal fistula, and a second intervention is often needed to avoid
      atrial fibrillation recurrence. For these reasons, a minimally-invasive device
      allowing performance of more complex treatments is still needed. High-intensity
      focused ultrasound (HIFU) can cause deep tissue lesions without damaging
      intervening tissues. Left atrial ultrasound-guided transesophageal HIFU ablation
      could have the potential to become a new ablation technique. The goal of this
      study was to design and test a minimally-invasive ultrasound-guided
      transesophageal HIFU probe under realistic treatment conditions. First, numerical
      simulations were conducted to determine the probe geometry, and to validate the
      feasibility of performing an AF treatment using a HIFU mini-maze (HIFUMM)
      procedure. Then, a prototype was manufactured and characterized. The 18-mm
      diameter probe head housing contained a 3-MHz spherical truncated HIFU transducer
      divided into 8 rings, with a 5-MHz commercial transesophageal echocardiography
      (TEE) transducer integrated in the center. Finally, ex vivo experiments were
      performed to test the impact of the esophagus layer between the probe and the
      tissue to treat, and also the influence of the lungs and the vascularization on
      lesion formation. First results show that this prototype successfully created ex
      vivo transmural myocardial lesions under ultrasound guidance, while preserving
      intervening tissues (such as the esophagus). Ultrasound-guided transesophageal
      HIFU can be a good candidate for treatment of AF in the future. 

PMID- 24658719
TI  - Estimation of multipath transmission parameters for quantitative ultrasound
      measurements of bone.
AB  - When applying quantitative ultrasound (QUS) measurements to bone for predicting
      osteoporotic fracture risk, the multipath transmission of sound waves frequently
      occurs. In the last 10 years, the interest in separating multipath QUS signals
      for their analysis awoke, and led to the introduction of several approaches.
      Here, we compare the performances of the two fastest algorithms proposed for QUS
      measurements of bone: the modified least-squares Prony method (MLSP), and the
      space alternating generalized expectation maximization algorithm (SAGE) applied
      in the frequency domain. In both approaches, the parameters of the transfer
      functions of the sound propagation paths are estimated. To provide an objective
      measure, we also analytically derive the Cramer-Rao lower bound of variances for
      any estimator and arbitrary transmit signals. In comparison with results of Monte
      Carlo simulations, this measure is used to evaluate both approaches regarding
      their accuracy and precision. Additionally, with simulations using typical QUS
      measurement settings, we illustrate the limitations of separating two
      superimposed waves for varying parameters with focus on their temporal
      separation. It is shown that for good SNRs around 100 dB, MLSP yields better
      results when two waves are very close. Additionally, the parameters of the
      smaller wave are more reliably estimated. If the SNR decreases, the parameter
      estimation with MLSP becomes biased and inefficient. Then, the robustness to
      noise of the SAGE clearly prevails. Because a clear influence of the
      interrelation between the wavelength of the ultrasound signals and their temporal
      separation is observable on the results, these findings can be transferred to QUS
      measurements at other sites. The choice of the suitable algorithm thus depends on
      the measurement conditions.

PMID- 24658720
TI  - 2-D tracking Doppler: a new method to limit spectral broadening in pulsed wave
      Doppler.
AB  - Transit time broadening is a major limitation in pulsed wave (PW) Doppler,
      especially when the angle between the flow direction and the ultrasound beam is
      large. The associated loss in frequency resolution may give severe overestimation
      of blood velocities, and finer details in the spectral display are lost. By using
      plane wave transmissions and parallel receive beamforming, multiple PW Doppler
      signals can be acquired simultaneously in a 2-D region. This enables tracking of
      the moving blood scatterers over a longer spatial distance to limit transit time
      broadening. In this work, the new method was tested using in vitro ultrasound
      recordings from a flow phantom, and in vivo recordings from a human carotid
      artery. The resulting 2-D tracking Doppler spectra showed significantly reduced
      spectral broadening compared with Doppler spectra generated by Welch's method.
      The reduction in spectral broadening was 4-fold when the velocity was 0.82 m/s
      and the beam-to-flow angle was 62 degrees . A signal model was derived and the
      expected Doppler power spectra were calculated, showing good agreement with
      experimental data. Improved spectral resolution was shown for beam-to-flow angles
      between 40 degrees  and 82 degrees . 

PMID- 24658721
TI  - Design considerations and performance of MEMS acoustoelectric ultrasound
      detectors.
AB  - Most single-element hydrophones depend on a piezoelectric material that converts
      pressure changes to electricity. These devices, however, can be expensive,
      susceptible to damage at high pressure, and/or have limited bandwidth and
      sensitivity. We have previously described the acoustoelectric (AE) hydrophone as
      an inexpensive alternative for mapping an ultrasound beam and monitoring acoustic
      exposure. The device exploits the AE effect, an interaction between electrical
      current flowing through a material and a propagating pressure wave. Previous
      designs required imprecise fabrication methods using common laboratory supplies,
      making it difficult to control basic features such as shape and size. This study
      describes a different approach based on microelectromechanical systems (MEMS)
      processing that allows for much finer control of several design features. In an
      effort to improve the performance of the AE hydrophone, we combine simulations
      with bench-top testing to evaluate key design features, such as thickness, shape,
      and conductivity of the active and passive elements. The devices were evaluated
      in terms of sensitivity, frequency response, and accuracy for reproducing the
      beam pattern. Our simulations and experimental results both indicated that
      designs using a combination of indium tin oxide (ITO) for the active element and
      gold for the passive electrodes (conductivity ratio = ~20) produced the best
      result for mapping the beam of a 2.25-MHz ultrasound transducer. Also, the AE
      hydrophone with a rectangular dumbbell configuration achieved a better beam
      pattern than other shape configurations. Lateral and axial resolutions were
      consistent with images generated from a commercial capsule hydrophone.
      Sensitivity of the best-performing device was 1.52 nV/Pa at 500 kPa using a bias
      voltage of 20 V. We expect a thicker AE hydrophone closer to half the acoustic
      wavelength to produce even better sensitivity, while maintaining high spectral
      bandwidth for characterizing medical ultrasound transducers. AE ultrasound
      detectors may also be useful for monitoring acoustic exposure during therapy or
      as receivers for photoacoustic imaging.

PMID- 24658722
TI  - Fuzzy similarity measures for detection and classification of defects in CFRP.
AB  - The systematic use of nondestructive testing assumes a remarkable importance
      where on-line manufacturing quality control is associated with the maintenance of
      complex equipment. For this reason, nondestructive testing and evaluation
      (NDT/NDE), together with accuracy and precision of measurements of the specimen,
      results as a strategic activity in many fields of industrial and civil interest.
      It is well known that nondestructive research methodologies are able to provide
      information on the state of a manufacturing process without compromising its
      integrity and functionality. Moreover, exploitation of algorithms with a low
      computational complexity for detecting the integrity of a specimen plays a
      crucial role in real-time work. In such a context, the production of carbon fiber
      resin epoxy (CFRP) is a complex process that is not free from defects and faults
      that could compromise the integrity of the manufactured specimen. Ultrasonic
      tests provide an effective contribution in identifying the presence of a defect.
      In this work, a fuzzy similarity approach is proposed with the goal of localizing
      and classifying defects in CFRP in terms of a sort of distance among signals
      (measure of ultrasonic echoes). A field-programmable gate array (FPGA)-based
      board will be also presented which implements the described algorithms on a
      hardware device. The good performance of the detection and classification
      achieved assures the comparability of the results with the results obtained using
      heuristic techniques with a higher computational load. 

PMID- 24658723
TI  - Omnidirectional Lamb waves by axisymmetrically-configured magnetostrictive patch
      transducer.
AB  - This work presents the generation of omnidirectional Lamb waves by a new
      magnetostrictive patch transducer (MPT) and investigates its generation
      mechanism. Although MPTs have been widely used for wave transduction in plates
      and pipes, no investigation reports the generation of omnidirectional Lamb waves
      in a plate by an MPT. For the generation, we propose an axisymmetrically
      configured MPT that installs multiple axisymmetric turns of coil outside of a
      permanent cylindrical magnet located above the center of a circular
      magnetostrictive patch. After confirming the omnidirectivity of the proposed MPT
      experimentally, the mechanism of the Lamb wave generation and its frequency
      characteristics are investigated. It is also shown that the Lamb wave is most
      efficiently generated in a test plate when its wavelength is equal to two-thirds
      of the magnetostrictive patch diameter. If this wavelength?patch diameter
      relation holds, the second radial extensional vibration mode of the patch of the
      proposed MPT is shown to be the mode responsible for generating the Lamb wave in
      a plate. 

PMID- 24658724
TI  - Simulation of ultrasonic array imaging of composite materials with defects.
AB  - Ultrasonic transducer arrays are extensively used for the nondestructive
      evaluation of materials for aerospace and other applications. However, their use
      with composites requires some technique development because of reflections at the
      layer boundaries and the effects of attenuation. When used in full matrix capture
      mode, algorithms such as the total focusing method (TFM) must be applied to
      obtain the image. In composite materials, improvement to the algorithm is
      required to include the effects of material anisotropy (affecting wave speed) and
      optimum aperture limits to optimize the signal-to-noise ratio and location
      detection for a defect in the material. This paper presents simulations of the
      ultrasonic array signals in multilayer anisotropic materials with and without a
      simulated defect. A kernel model for plane wave propagation in the material is
      combined with an angular spectrum decomposition (for finite transducer elements)
      and transducer frequency response, to model the full array signals. Inclusion of
      the defect is through its far-field scattering response. The model facilitates
      the study of imaging algorithm development by identification of the effects of
      anisotropy, signal-to-noise ratio, and aperture limit. An analytical method for
      the calculation of the effective group velocity in the composite at low frequency
      is demonstrated, permitting rapid calculation of time delay laws in practice.

PMID- 24658725
TI  - Design and manufacturing of a piezoelectric traveling-wave pumping device.
AB  - In this article, we present the design and construction of a micropump exhibiting
      a nontraditional pumping principle whose design is achievable at very low scales.
      The operation is based on the action of a mechanical traveling wave deforming the
      bottom wall of a flexible channel containing a fluid. The paper treats for the
      first time the influence of the traveling wave parameters on the performance of
      the pump with the help of finite element simulations. The results obtained from
      the simulation are subsequently used for the dimensioning of the linear
      ultrasonic traveling wave actuator that drives the device. Finally, a very simple
      channel-reservoirs structure was conceived to test the device. At this point,
      several measurements of flow rate and back pressure were carried out to estimate
      the performance of the prototype for different values of wave amplitude. The
      article finishes with a comparison between the numerical and experimental results
      and a brief section of discussion and conclusions. 

PMID- 24658726
TI  - Effects of interface bonding on acoustic wave generation in an elastic body by
      surface-mounted piezoelectric transducers.
AB  - We study the effects of interface bonding on acoustic wave generation in an
      elastic body using surface-mounted piezoelectric transducers driven electrically.
      A theoretical analysis is performed based on a physical model of a piezoelectric
      layer on an elastic substrate. The transducer-substrate interface is described by
      the shear-slip model, representing a viscoelastic interface. Different from the
      results in the literature on free vibrations of structures with weak interfaces,
      this paper presents an electrically forced vibration analysis. An analytical
      solution for the generated acoustic wave is obtained and used to calculate its
      energy flux and the efficiency of the transduction. The effects of the interface
      parameters are examined. It is found that the interface bonding affects the
      performance of the transducer in multiple ways, some of which may be exploitable
      in designs for better transducer performance. In particular, optimal transduction
      is not necessarily associated with a perfectly bonded interface.

PMID- 24658727
TI  - Ultrasonic manipulation of particles in an open fluid film.
AB  - Ultrasonic manipulation is a noncontact method of trapping and holding particles
      in suspension, and has found many applications in microfluidic systems.
      Typically, ultrasonic standing waves are used; this approach is well established
      in fully enclosed microfluidic systems consisting of channels or chambers with an
      attached piezoelectric actuator. In this work, we examine the use of ultrasonic
      manipulation in open fluid films, which offer a high degree of accessibility. A
      piezoelectric actuator is presented which can be lowered into a separate fluid
      tray. This two-part system offers a high degree of flexibility; indeed the
      actuator can be removed with little disturbance to the particle patterns, so
      manipulation could potentially be periodically applied as required. Particle
      manipulation is shown to be possible over a distance many times the size of the
      actuator. Furthermore, particle manipulation can also be achieved in a tilted
      fluid film, so alignment between the two parts of the system is not critical to
      its operation. 

PMID- 24658728
TI  - Volume dependence in Handel's model of quartz crystal resonator noise.
AB  - Although criticized by many, Handel's quantum model for 1/f noise remains the
      only model giving a quantitative estimation of the level of intrinsic 1/f noise
      in quartz crystal resonators that is compatible with the best experimental
      results. In this paper, we reconsider the volume dependence in this model. We
      first argue that an acoustic volume, representing the volume in which the
      vibration energy is trapped, should be used instead of the geometrical volume
      between the electrodes. Then, we show that because there is an implicit
      dependence of the quality factor of the resonator with its thickness, the net
      effect of Handel's formula is not an increase of noise proportionally to the
      thickness of the resonator, as could be naively expected, but a net decrease when
      thickness increases. Finally, we show that a plot of Q(4)Sy versus the acoustic
      volume, instead of the usual Sy plot, could be useful to compare the quality of
      acoustic resonators having very different resonance frequencies. 

PMID- 24658729
TI  - Low-loss lateral-extensional piezoelectric filters on ultrananocrystalline
      diamond.
AB  - In this work, lateral-extensional thin-film piezoelectric- on-diamond (TPoD)
      filters with very low insertion loss (IL) values (<4 dB) are reported. Two
      different lateral-extensional modes of a resonant structure are coupled together
      to realize a two-pole filter. The filters of this work exhibit low IL values,
      with fractional bandwidth between 0.08% and 0.2%, and have a very small
      footprint. This paper reports on the lowest IL in the literature for lateral
      extensional thin-film piezoelectric filters with 50 Omega terminations in the GSM
      frequency band (~900 MHz). The narrow-band filters of this work are fabricated on
      three ultrananocrystalline diamond substrates to achieve higher frequencies
      without excessive reduction in the feature size. The paper also thoroughly
      studies the parameters that affect the performance of such filters and then
      discussions are evaluated by the statistical data collected from the fabricated
      wafers.

PMID- 24658730
TI  - An equivalent network representation of a clamped bimorph piezoelectric
      micromachined ultrasonic transducer with circular and annular electrodes using
      matrix manipulation techniques.
AB  - An electric circuit model for a clamped circular bimorph piezoelectric
      micromachined ultrasonic transducer (pMUT) was developed for the first time. The
      pMUT consisted of two piezoelectric layers sandwiched between three thin
      electrodes. The top and bottom electrodes were separated into central and annular
      electrodes by a small gap. While the middle electrode was grounded, the central
      and annular electrodes were biased with two independent voltage sources. The
      strain mismatch between the piezoelectric layers caused the plate to vibrate and
      transmit a pressure wave, whereas the received echo generated electric charges
      resulting from plate deformation. The clamped pMUT plate was separated into a
      circular and an annular plate, and the respective electromechanical
      transformation matrices were derived. The force and velocity vectors were
      properly selected using Hamilton's principle and the necessary boundary
      conditions were invoked. The electromechanical transformation matrix for the
      clamped circular pMUT was deduced using simple matrix manipulation techniques.
      The pMUT performance under three biasing schemes was elaborated: 1) central
      electrode only, 2) central and annular electrodes with voltages of the same
      magnitude and polarity, and 3) central and annular electrodes with voltages of
      the same magnitude and opposite polarity. The circuit parameters of the pMUT were
      extracted for each biasing scheme, including the transformer ratio, the clamped
      electric impedance, and the open-circuit mechanical impedance. Each pMUT scheme
      was characterized under different acoustic loadings using the theoretically
      developed model, which was verified with finite element modeling (FEM)
      simulation. The electrode size was optimized to maximize the electromechanical
      transformer ratio. As such, the developed model could provide more insight into
      the design, optimization, and characterization of pMUTs and allow for performance
      comparison with their cMUT counterparts. 

PMID- 24658731
TI  - A hybrid transducer to magnetically and ultrasonically evaluate magnetic fluids.
AB  - Ultrasound, magnetic fields, and optical techniques have been explored for
      clinical diagnosis and therapy. However, these techniques have limitations. In
      this study, we constructed and characterized a transducer to magnetically and
      ultrasonically investigate samples labeled with magnetic particles. The
      transducer is a hybrid system consisting of an ac biosusceptometer (ACB) and an
      ultrasonic transducer. The basic operation principle consisted of measuring the
      magnetization and microvibrations of ferromagnetic particles (37 and 70 MUm)
      mixed in yogurt and excited by an external alternating magnetic field generated
      by the ACB's excitation coils. The vibration of the ferromagnetic particles was
      measured in phantoms using a Doppler ultrasonic transducer; we verified the
      sensitivity to detecting the vibrations at low concentrations of ferromagnetic
      material (~1%). The responses of the susceptometer and Doppler ultrasound
      linearly depended on the voltage level applied to the magnetizing coils at low
      ferromagnetic particle concentrations (? 5%). We also conducted a repeatability
      test on the prototype, which indicated a deviation of 0.94% and 0.25% in the
      Doppler and susceptometric measurements, respectively. We can conclude that the
      hybrid transducer technique has potential clinical applications. 

PMID- 24658732
TI  - Piezoelectric polymer multilayer on flexible substrate for energy harvesting.
AB  - A piezoelectric polymer multilayer structure formed on a flexible substrate is
      investigated for mechanical energy harvesting under bending mode. Analytical and
      numerical models are developed to clarify the effect of material parameters
      critical to the energy harvesting performance of the bending multilayer
      structure. It is shown that the maximum power is proportional to the square of
      the piezoelectric stress coefficient and the inverse of dielectric permittivity
      of the piezoelectric polymer. It is further found that a piezoelectric multilayer
      with thinner electrodes can generate more electric energy in bending mode. The
      effect of improved impedance matching in the multilayer polymer on energy output
      is remarkable. Comparisons between piezoelectric ceramic multilayers and polymer
      multilayers on flexible substrate are discussed. The fabrication of a P(VDF-TrFE)
      multilayer structure with a thin Al electrode layer is experimentally
      demonstrated by a scalable dip-coating process on a flexible aluminum substrate.
      The results indicate that it is feasible to produce a piezoelectric polymer
      multilayer structure on flexible substrate for harvesting mechanical energy
      applicable for many low-power electronics. 

PMID- 24658733
TI  - Optical micromachined ultrasound transducers (OMUT)--a new approach for high
      frequency transducers.
AB  - The sensitivity and reliability of piezoelectric ultrasound transducers severely
      degrade in applications requiring high frequency and small element size.
      Alternative technologies such as capacitive micromachined ultrasound transducers
      (CMUT) and optical sensing and generation of ultrasound have been proposed and
      studied for several decades. In this paper, we present a new type of device based
      on optical micromachined ultrasound transducer (OMUT) technology. OMUTs rely on
      microfabrication techniques to construct micrometerscale air cavities capped by
      an elastic membrane. A modified photoresist bonding process has been developed to
      facilitate the fabrication of these devices. We will describe the design,
      fabrication, and testing of prototype OMUT devices which implement a receive-only
      function. Future design modifications are proposed for incorporating complete
      transmit?receive functionality in a single element. 

PMID- 24658734
TI  - The modified design of ring electrode quartz crystal resonator for uniform mass
      sensitivity distribution.
AB  - The mass sensitivity distribution curve of quartz crystal resonators (QCRs) with
      common circular electrodes is bell-shaped; however, a uniform mass sensitivity
      distribution is expected for highly accurate and repeatable measuring results.
      Pioneers designed a ring electrode QCR with a bimodal distribution curve of mass
      sensitivity, and an obvious concavity is presented between two peak points for a
      fundamental operating frequency of 10 MHz. The concavity is an obstacle to
      uniform mass sensitivity distribution, so eliminating the concavity is the goal
      of this study; two methods-changing overtone order and designing electrode
      geometry-are proposed to do so. An analytical theory for sensitivity distribution
      is introduced in this paper first. Analysis results show that the fifth overtone
      of 10 MHz is desirable for eliminating the concavity but with a drawback of
      sacrificing absolute mass sensitivity. The method of designing the electrode
      geometry can overcome this drawback and dot-ring and double-ring electrode
      geometries are proposed. When electrode parameters were selected properly, the
      maximum difference of mass sensitivity between two peak points was reduced by
      about 42.21% for dot-ring electrode QCR and 77.63% for double-ring electrode QCR
      compared with that of ring electrode QCR. 

PMID- 24658735
TI  - Both GtfA and GtfB are required for SraP glycosylation in Staphylococcus aureus.
AB  - Staphylococcus aureus has been shown to bind to human platelets through a variety
      of surface molecules, including serine-rich adhesin for platelets (SraP). The
      SraP mutant strain of S. aureus is significantly impaired in its ability to
      initiate infection compared with the wild strain. SraP is a cell wall-anchored,
      glycosylated protein. A previous study revealed that SecY2, Asp1, Asp2, Asp3, and
      SecA2 in the SraP operon were required for the efficient transport of
      glycosylated SraP from the cytoplasm to the bacterial cell surface. However, no
      glycosyltransferase (Gtf) was found to be involved in the glycosylation of SraP.
      In this study, SraP was found in all of the 55 clinical isolates of S. aureus
      using a real-time polymerase chain reaction assay. Sequence and phylogenetic
      analysis showed that GtfA and GtfB in the SraP operon were highly conserved in
      most of these clinical isolates. Conserved domains analysis revealed that both
      GtfA and GtfB contained a GT1_GtfA-like domain. Structural homology analysis
      inferred that they are both Gtfs. We then constructed an in vivo glycosylation
      system in Escherichia coli using SraP1-743 as the substrate and GtfA and GtfB as
      the Gtfs. Using this system, we found that GtfA and GtfB were the Gtfs that
      transferred the N-acetylglucosamine-containing oligosaccharides to the
      recombinant SraP1-743. Deletion of either one or both of the Gtfs abolished the
      glycosylation of SraP. In summary, GtfA and GtfB in the SraP operon are highly
      conserved in most clinical isolates of S. aureus, and both GtfA and GtfB are
      required for SraP glycosylation.

PMID- 24658736
TI  - Choroidal thickness changes with photodynamic therapy  for a diffuse choroidal
      hemangioma in Sturge-Weber  syndrome.
AB  - The aim of this study was to evaluate the choroidal thickness (CT) changes
      associated with visual function following photodynamic therapy (PDT) for a
      diffuse choroidal hemangioma in Sturge-Weber syndrome. We report a case of Sturge
      Weber syndrome and symptomatic serous retinal detachment (SRD) with diffuse
      choroidal hemangioma treated with PDT. Visual acuity (VA), macular sensitivity
      measured by means of MP1 microperimeter (Nidek Technologies, Padova, Italy),
      retinal and CT, measured by means of enhanced depth optical coherence tomography
      (EDI-OCT, Spectralis, Heidelberg Engineering, Heidelberg, Germany) were analyzed
      at baseline, 3 and 12 months follow-up.After the PDT VA and macular sensitivity
      improved.The OCT examination showed the resolution of SRD. The choroid was
      measured after PDT using EDI-OCT. At baseline, the subfoveal CT showed a
      progressive thickness reduction from 251 to 83 lm during follow-up. To our
      knowledge, this is the first report of CT changes after PDT for a diffuse
      choroidal hemangioma in Sturge-Weber syndrome in a longterm follow-up. The CT
      measurement represents a potential parameter to better follow choroidal
      hemangiomas and their response to treatment. However,the long-term choroidal
      changes should be carefully taken into account.

PMID- 24658737
TI  - Identification of novel knockout and up-regulated targets  for improving
      isoprenoid production in E. coli.
AB  - Discovery of novel potential genetic targets to increase the supply of isoprenoid
      precursors, isopentyl/dimethylallyl diphosphate, is of importance for microbial
      production of isoprenoids. Here, to improve isoprenoid precursor supply, a flux
      distribution comparison analysis, based on the genome-scale model, was utilized
      to simultaneously predict the knockout, down- and up-regulated targets in
      Escherichia coli. 51 targets were in silico discovered. All knockout and up
      regulated targets were experimentally tested to enhance lycopene production. Five
      knockout targets (deoB, yhfw, yahI, pta and eutD) and four up-regulated targets
      (ompN, ompE, ndk and cmk) led to 10-45% increases of lycopene yield,
      respectively, which had not been uncovered in previous studies. When engineering
      of the five most significant targets gdhA, eutD, tpiA, ompE and ompN, were
      combined the lycopene titer improved by 174% in shake-flask and 81% in bioreactor
      fermentations with a maximum yield of 454 mg l(-1).

PMID- 24658738
TI  - Long-term stability in biomass and production of terpene   indole alkaloids by
      hairy root culture of Rauvolfia serpentina   and cost approximation to endorse
      commercial realism.
AB  - The effect of 6 years of cultivation and use of table-sugar (TS) on the
      biomass/terpene alkaloid productivities and rol gene expression were studied in a
      hairy root (HR) clone of Rauvolfia serpentina. The media cost could be reduced
      >94 % by replacing sucrose (SUC) with TS-an unexplored avenue for HR cultivation.
      The overall productivities increased over long-term cultivation with sugar
      proving superior to SUC for biomass (24.4 +/- 2.11 g/l DW after 40 days to 17.31
      % higher) and reserpine (0.094 +/- 0.008 % DW after 60 days to 193.8 % more)
      production. The latter however revealed comparatively better yields concerning
      ajmaline (0.507 +/- 0.048 % DW after 60 days to 61.98 % higher) and yohimbine
      (0.628 +/- 0.062 % DW after 60 days to 38.32 % higher), respectively. PCR
      amplification of rol genes confirmed long-term expression stability.

PMID- 24658739
TI  - The role of EaIkappaB-alpha, an IkappaB-alpha homologue in Epinephelus akaara,
      involved in innate immune response.
AB  - The inhibitor kappaB (IkappaB) protein is an important component of the nuclear
      factor kB (NF-kappaB) signaling pathway. We have cloned and characterized the
      IkappaB-alpha homologue gene (named EaIkappaB-alpha) from grouper (Epinephelus
      akaara), expressed it in Escherichia coli and generated a rabbit polyclonal
      antibody. EaIkappaB-alpha encodes a 308-amino acid protein with evolutionarily
      and functionally homology to mammalian IkappaB-alpha. Over-expression of wild
      type EaIkappaB-alpha or a mutated, nondegradable EaIkappaB-alpha (EaIkappaB
      alphaM) in Escherichia coli both inhibited the degradation of cellular EaIkappaB
      alpha, activation of NF-kappaB and expression of tumor necrosis factor alpha (TNF
      alpha). EaIkappaB-alpha protein is restricted to the cytoplasm in unstimulated
      cell. Activated by diverse stimuli, EaIkappaB-alpha is degraded, thereby
      releasing NF-kappaB into nucleus and activating NF-kappaB-mediated transcripts.
      EaIkappaB-alpha and other studied NF-kappaB target genes are induced by LPS in
      kidney and liver, which suggests that EaIkappaB-alpha may play an important role
      in immune response of grouper.

PMID- 24658740
TI  - Maintenance of human adipose derived stem cell (hASC)   differentiation
      capabilities using a 3D culture.
AB  - In this study, 3D culture system for human adipose-derived stem cell (hASC) using
      a BioLevitator as the bioreactor for microcarrier-based cultures was established.
      During the culturing period, hASCs preferred to grow in crevices between
      microcarriers and a high viability was maintained even when reaching confluency.
      Adipogenic or osteogenic differential medium was used to induce hASCs and
      differential potentials of these cells were compared between 2D and 3D
      environments via RT-PCR and staining quantifications. CEBP/alpha gene expression
      was significant higher in 3D condition at day 21 (P < 0.05). Staining
      quantification indicates that cells cultured in 3D condition have significant
      better differentiation potential from day 14 to 21 for both adipogenic and
      osteogenic lineages (P < 0.01).

PMID- 24658741
TI  - Metabolomics reveals stage-specific metabolic pathways   of microbial communities
      in two-stage anaerobic   fermentation of corn-stalk.
AB  - Analysis of intracellular metabolites is essential to delineate metabolic
      pathways of microbial communities for evaluation and optimization of anaerobic
      fermentation processes. The metabolomics are reported for a microbial community
      during two stages of anaerobic fermentation of corn stalk in a biogas digester
      using GC-MS. Acetonitrile/methanol/water (2:2:1, by vol) was the best extraction
      solvent for microbial community analysis because it yielded the largest number of
      peaks (>200), the highest mean summed value of identified metabolites (23) and
      the best reproducibility with a coefficient of variation of 30 % among four
      different extraction methods. Inter-stage comparison of metabolite profiles
      showed increased levels of sugars and sugar alcohols during methanogenesis and
      fatty acids during acidogenesis. Identification of stage-specific metabolic
      pathways using metabolomics can therefore assist in monitoring and optimization
      of the microbial community for increased biogas production during anaerobic
      fermentation.

PMID- 24658742
TI  - Challenges and recent advances in affinity purification   of tag-free proteins.
AB  - There is currently no generic, simple, lowcost method for affinity
      chromatographic purification of proteins in which the purified product is free of
      appended tags. Existing approaches for the purification of tagless proteins fall
      into two broad categories: (1) direct affinity-based capture of tag-free proteins
      that utilize affinity ligands specific to the target protein or class of target
      protein, and (2) removal of an appended affinity tag following tag-mediated
      protein capture. This paper reviews current state-of-the-art approaches for
      tagless protein purification in both categories, including specific examples of
      affinity ligands used for the capture of different classes of proteins and
      cleavage systems for affinity tag removal following chromatographic capture. A
      particular focus of this review is on recent developments in affinity tag removal
      systems utilizing split inteins.

PMID- 24658743
TI  - Disease resistance in rice and the role of molecular breeding   in protecting
      rice crops against diseases.
AB  - Rice diseases (bacterial, fungal, or viral) threaten food productivity. Host
      resistance is the most efficient, environmentally friendly method to cope with
      such diverse pathogens. Quantitative resistance conferred by quantitative trait
      loci (QTLs) is a valuable resource for rice disease resistance improvement.
      Although QTLs confer partial but durable resistance to many pathogen species in
      different crop plants, the molecular mechanisms of quantitative disease
      resistance remain mostly unknown. Quantitative resistance and non-host resistance
      are types of broad-spectrum resistance, which are mediated by resistance (R)
      genes. Because R genes activate different resistance pathways, investigating the
      genetic spectrum of resistance may lead to minimal losses from harmful diseases.
      Genome studies can reveal interactions between different genes and their pathways
      and provide insight into gene functions. Protein-protein interaction (proteomics)
      studies using molecular and bioinformatics tools may further enlighten our
      understanding of resistance phenomena.

PMID- 24658744
TI  - Understanding copper sensitivity in zebrafish (Danio rerio) through the
      intracellular localization of copper transporters in a hepatocyte cell-line ZFL
      and the tissue expression profiles of copper transporters.
AB  - Zebrafish (Danio rerio) is a freshwater fish species of Cyprinidae known for its
      copper (Cu) intolerance, yet the underlying mechanisms of the sensitivity remain
      unclear. In this study, we examined the highly conserved molecular machineries in
      the copper handling system, namely ATOX1, ATP7A, ATP7B, and CTR1, by profiling
      their gene expression patterns among tissues before and after acute waterborne Cu
      exposure, and investigating their intracellular localization patterns using a
      zebrafish hepatocyte cell line, ZFL. We found that ATP7B was weak in its response
      toward Cu exposure to elicit its copper efflux function. Tissue distribution of
      these Cu transporters, however, revealed a distinct expression profile compared
      with mammals and other fish, particularly ATP7A, which unlike ATP7B was highly
      expressed in the liver, while ATP7B, not ATP7A, was specifically expressed in the
      intestine. ATOX1 transcript expression was also found to be significantly up
      regulated with acute waterborne Cu, in contrast to the decreased expression found
      in other fish. A possible explanation for the Cu sensitivity in zebrafish is
      discussed. 

PMID- 24658745
TI  - Subthalamic nucleus involvement in executive functions with increased cognitive
      load: a subthalamic nucleus and anterior cingulate cortex depth recording study.
AB  - We studied the appearance of broadband oscillatory changes (ranging 2-45 Hz)
      induced by a cognitive task with two levels of complexity. The event-related
      de/synchronizations (ERD/S) in the subthalamic nucleus (STN) and in the anterior
      cingulate cortex (ACC) were evaluated in an executive function test. Four
      epilepsy surgery candidates with intracerebral electrodes implanted in the ACC
      and three Parkinson's disease patients with externalized deep brain stimulation
      electrodes implanted in the STN participated in the study. A Flanker test (FT)
      with visual stimuli (arrows) was performed. Subjects reacted to four types of
      stimuli presented on the monitor by pushing the right or left button: congruent
      arrows to the right or left side (simple task) and incongruent arrows to the
      right or left side (more difficult complex task). We explored the activation of
      STN and the activation of the ACC while processing the FT. Both conditions, i.e.
      congruent and incongruent, induced oscillatory changes in the ACC and also STN
      with significantly higher activation during incongruent trial. At variance with
      the ACC, in the STN not only the ERD beta but also the ERD alpha activity was
      significantly more activated by the incongruent condition. In line with our
      earlier studies, the STN appears to be involved in activities linked with
      increased cognitive load. The specificity and complexity of task-related
      activation of the STN might indicate the involvement of the STN in processes
      controlling human behaviour, e.g. in the selection and inhibition of competing
      alternatives.

PMID- 24658747
TI  - Reversible cerebral vasoconstriction syndrome: updates and new perspectives.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is an important cause of
      headaches that can lead to other neurological complications, including stroke, if
      not recognized early. Over the past few years, there has been great progress in
      the recognition of this entity. However, there is still much to be learned about
      its pathophysiology and optimal treatment strategies. RCVS occurs mostly in
      middle-aged adults, and there is a female preponderance with an increased
      incidence during the postpartum period. A consistent, predominating feature is a
      sudden-onset, severe headache that is frequently recurrent, usually over the span
      of a week. Less common presentations include seizures or focal neurological
      symptoms. Important causative factors include vasoactive medications, as well as
      illicit drugs like marijuana and cocaine. The current underlying pathophysiology
      is thought to be a disturbance in cerebrovascular tone leading to
      vasoconstriction. The diagnosis is based on history, physical examination, and
      cerebrovascular imaging findings that demonstrate multifocal, segmental areas of
      vasoconstriction in large- and medium-sized arteries. An important criterion for
      making the diagnosis is the eventual reversibility of symptoms and imaging
      findings. 

PMID- 24658746
TI  - Adenovirus-mediated gene transfer in mesenchymal stem cells can be significantly
      enhanced by the cationic polymer polybrene.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitors, which can undergo self
      renewal and give rise to multi-lineages. A great deal of attentions have been
      paid to their potential use in regenerative medicine as potential therapeutic
      genes can be introduced into MSCs. Genetic manipulations in MSCs requires
      effective gene deliveries. Recombinant adenoviruses are widely used gene transfer
      vectors. We have found that although MSCs can be infected in vitro by
      adenoviruses, high virus titers are needed to achieve high efficiency. Here, we
      investigate if the commonly-used cationic polymer Polybrene can potentiate
      adenovirus-mediated transgene delivery into MSCs, such as C2C12 cells and iMEFs.
      Using the AdRFP adenovirus, we find that AdRFP transduction efficiency is
      significantly increased by Polybrene in a dose-dependent fashion peaking at 8
      MUg/ml in C2C12 and iMEFs cells. Quantitative luciferase assay reveals that
      Polybrene significantly enhances AdFLuc-mediated luciferase activity in C2C12 and
      iMEFs at as low as 4 MUg/ml and 2 MUg/ml, respectively. FACS analysis indicates
      that Polybrene (at 4 MUg/ml) increases the percentage of RFP-positive cells by
      approximately 430 folds in AdRFP-transduced iMEFs, suggesting Polybrene may
      increase adenovirus infection efficiency. Furthermore, Polybrene can enhance
      AdBMP9-induced osteogenic differentiation of MSCs as early osteogenic marker
      alkaline phosphatase activity can be increased more than 73 folds by Polybrene (4
      MUg/ml) in AdBMP9-transduced iMEFs. No cytotoxicity was observed in C2C12 and
      iMEFs at Polybrene up to 40 MUg/ml, which is about 10-fold higher than the
      effective concentration required to enhance adenovirus transduction in MSCs.
      Taken together, our results demonstrate that Polybrene should be routinely used
      as a safe, effective and inexpensive augmenting agent for adenovirus-mediated
      gene transfer in MSCs, as well as other types of mammalian cells. 

PMID- 24658749
TI  - Rare-earth alkyl complexes supported by formamidinate ligands: synthesis,
      structure, and catalytic activity for isoprene polymerization.
AB  - A series of rare-earth metal monoalkyl complexes supported by N,N'-di(2,6
      dialkylphenyl)formamidinate ligand (L)2RECH2SiMe3.thf [L(1) = HC(N-2,6-Me2C6H3)2,
      RE = Y (1), L(2) = HC(N-2,6-(i)Pr2C6H3)2, RE = Y (2), Er (3), Dy (4), Sm (5), and
      Nd (6)] were synthesized by alkyl elimination reaction or by salt metathesis
      reaction in good yields. All complexes were characterized by elemental analyses,
      FT-IR spectroscopy and single crystal X-ray diffraction. In combination with
      [Ph3C][B(C6F5)4] and alkylaluminium, these complexes displayed a good activity
      towards isoprene polymerization to give polyisoprenes with high molecular weight
      (M(n) > 10(4)) and narrow molecular distribution (PDI < 2.0). The influence of
      alkylaluminium, central metal, temperature, sequence of addition of
      alkylaluminium and [Ph3C][B(C6F5)4] on the polymerization of isoprene was
      studied. It was interesting to find that addition of the cocatalysts sequence has
      a great influence on the regioselectivity of the polymerization. High 1,4
      regioselectivity polymerizations of isoprene (as high as 98%) were observed when
      the catalysts were added in the order [RE]/[alkylaluminum]/[borate].

PMID- 24658748
TI  - Additional molecular findings in 11p15-associated imprinting disorders: an urgent
      need for multi-locus testing.
AB  - The chromosomal region 11p15 contains two imprinting control regions (ICRs) and
      is a key player in molecular processes regulated by genomic imprinting. Genomic
      as well as epigenetic changes affecting 11p15 are associated either with Silver
      Russell syndrome (SRS) or Beckwith-Wiedemann syndrome (BWS). In the last years, a
      growing number of patients affected by imprinting disorders (IDs) have reported
      carrying the disease-specific 11p15 hypomethylation patterns as well as
      methylation changes at imprinted loci at other chromosomal sites (multi-locus
      methylation defects, MLMD). Furthermore, in several patients, molecular
      alterations (e.g., uniparental disomies, UPDs) additional to the primary
      epimutations have been reported. To determine the frequency and distribution of
      mutations and epimutations in patients referred as SRS or BWS for genetic
      testing, we retrospectively ascertained our routine patient cohort consisting of
      711 patients (SRS, n = 571; BWS, n = 140). As this cohort represents the typical
      cohort in a routine diagnostic lab without clinical preselection, the detection
      rates were much lower than those reported from clinically characterized cohorts
      in the literature (SRS, 19.9%; BWS, 28.6%). Among the molecular subgroups known
      to be predisposed to MLMD, the frequencies corresponded to that in the literature
      (SRS, 7.1% in ICR1 hypomethylation carriers; BWS, 20.8% in ICR2 hypomethylation
      patients). In several patients, more than one epigenetic or genetic disturbance
      could be identified. Our study illustrates that the complex molecular alterations
      as well as the overlapping and sometimes unusual clinical findings in patients
      with imprinting disorders (IDs) often make the decision for a specific imprinting
      disorder test difficult. We therefore suggest to implement molecular assays in
      routine ID diagnostics which allow the detection of a broad range of
      (epi)mutation types (epimutations, UPDs, chromosomal imbalances) and cover the
      clinically most relevant known ID loci because of the following: (a) Multi-locus
      tests increase the detection rates as they cover numerous loci. (b) Patients with
      unexpected molecular alterations are detected. (c) The testing of rare imprinting
      disorders becomes more efficient and quality of molecular diagnosis increases.
      (d) The tests identify MLMDs. In the future, the detailed characterization of
      clinical and molecular findings in ID patients will help us to decipher the
      complex regulation of imprinting and thereby providing the basis for more
      directed genetic counseling and therapeutic managements in IDs. KEY MESSAGE:
      Molecular disturbances in patients with imprinting disorders are often not
      restricted to the disease-specific locus but also affect other chromosomal
      regions. These additional disturbances include methylation defects, uniparental
      disomies as well as chromosomal imbalances. The identification of these
      additional alterations is mandatory for a well-directed genetic counseling.
      Furthermore, these findings help to decipher the complex regulation of
      imprinting.

PMID- 24658750
TI  - Characterisation and comparison of lactating mouse and bovine mammary gland
      miRNomes.
AB  - BACKGROUND: The mammary gland is a dynamic organ that undergoes important
      physiological changes during reproductive cycles. Until now, data regarding the
      characterisation of miRNA in the mammary gland have been scarce and mainly
      focused on their abnormal expression in breast cancer. Our goal was to
      characterise the microRNA (miRNA) involved in mechanisms regulating the mammary
      function, with particular focus on the lactation stage. METHODOLOGY/PRINCIPAL
      FINDINGS: Using high-throughput sequencing technology, the exhaustive repertoires
      of miRNA expressed (miRNome) in mouse and bovine mammary glands during
      established lactation were identified, characterized and compared. Furthermore,
      in order to obtain more information on miRNA loading in the RNA-induced silencing
      complex (RISC), the miRNome was compared with that obtained from RNA associated
      with the AGO2 protein (AGO2-miRNome) in mouse lactating mammary gland. This study
      enabled the identification of 164 and 167 miRNA in mouse and bovine,
      respectively. Among the 30 miRNA most highly expressed in each species, 24 were
      common to both species and six of them were preferentially highly expressed in
      lactating than non-lactating mammary gland. The potential functional roles of
      these 24 miRNA were deduced using DIANA-miRPath software, based on miRNA/mRNA
      interactions. Moreover, seven putative novel miRNA were identified. Using DAVID
      analysis, it was concluded that the predicted targets of two of these putative
      novel miRNA are involved in mammary gland morphogenesis. CONCLUSION/SIGNIFICANCE:
      Our study provides an overview of the characteristics of lactating mouse and
      bovine mammary gland miRNA expression profiles. Moreover, species-conserved miRNA
      involved in this fundamental biological function were identified. These miRNomes
      will now be used as references for further studies during which the impact of
      animal breeding on the miRNA expression will be analysed.

PMID- 24658763
TI  - Post-esophagectomy tube feeding: a retrospective comparison of jejunostomy and a
      novel gastrostomy feeding approach.
AB  - BACKGROUND: McKeown-type esophagectomy combined with retrosternal reconstruction
      is a common surgical treatment for esophageal cancer. Various enteral feeding
      options are available post-esophagectomy, but no definitive preference exists.
      METHOD: "Retrosternal Route Gastrostomy Feeding (RGF)" was developed as an
      alternative enteral feeding approach that requires few additional surgical
      interventions. RGF is based on McKeown-type esophagectomy. We retrospectively
      compared RGF (n = 121) to jejunostomy feeding (JF) (n = 153) in 274 patients at
      the Department of Cardiothoracic Surgery in Changzheng Hospital (Shanghai, China)
      between June 2008 and Sept. 2012. Data pertaining to efficacy and procedural
      complications were compared among patients. RESULTS: RGF had a significantly
      shorter postoperative hospital stay (11 vs. 15 days, p<0.001) and time to removal
      of the feeding tube (9 vs. 14 days, p<0.001) compared to JF. Bowel obstruction
      (0.0% vs. 7.2% p = 0.003), abdominal distension (9.1% vs. 19% p = 0.022), and the
      occurrence of pneumonia (11.6% vs. 26.1% p = 0.003) were significantly lower in
      the RGF group. Feeding tube related complications and the associated morbidity
      rate were reduced in the RGF group. The two groups had similar tolerance to
      surgery. CONCLUSION: Our data suggests that RGF is a safe post-esophagectomy
      enteral feeding alternative to JF.

PMID- 24658764
TI  - Habitat partitioning and morphological differentiation: the  Southeast Asian
      Draco lizards and Caribbean Anolis lizards  compared.
AB  - Sympatric species that initially overlap in resource use are expected to
      partition the environment in ways that will minimize interspecific competition.
      This shift in resource use can in turn prompt evolutionary changes in morphology.
      A classic example of habitat partitioning and morphological differentiation are
      the Caribbean Anolis lizards. Less well studied, but nevertheless striking
      analogues to the Anolis are the Southeast Asian Draco lizards. Draco and Anolis
      have evolved independently of each other for at least 80 million years. Their
      comparison subsequently offers a special opportunity to examine mechanisms of
      phenotypic differentiation between two ecologically diverse, but phylogenetically
      distinct groups. We tested whether Draco shared ecological axes of
      differentiation with Anolis (e.g., habitat use), whether this differentiation
      reflected interspecific competition, and to what extent adaptive change in
      morphology has occurred along these ecological axes. Using existing data on
      Anolis, we compared the habitat use and morphology of Draco in a field study of
      allopatric and sympatric species on the Malay Peninsula, Borneo and in the
      Philippines. Sympatric Draco lizards partitioned the environment along common
      resource axes to the Anolis lizards, especially in perch use. Furthermore, the
      morphology of Draco was correlated with perch use in the same way as it was in
      Anolis: species that used wider perches exhibited longer limb lengths. These
      results provide an important illustration of how interspecific competition can
      occur along common ecological axes in different animal groups, and how natural
      selection along these axes can generate the same type of adaptive change in
      morphology.

PMID- 24658765
TI  - On the 4-H Study of Positive Youth Development.
AB  - The research reported in this issue advances our understanding of the multiple
      interactive influences on young people's development. The study invokes
      Relational Developmental Systems Theory to show, among other findings, how the
      impact of out-of-school time depends on the number and range of different types
      of activities young people engage in. The study also demonstrates that
      developmental assets (the 5 Cs) can co-exist with problem behavior, an important
      contribution to the positive youth development perspective. Readers will also
      find in these articles diverse strategies of data analysis and exemplars of
      research that informs practice as well as theory.

PMID- 24658766
TI  - Balancing ischaemia and bleeding with dual antiplatelet therapy: a resolute
      endeavour.

PMID- 24658768
TI  - Non-cardiac surgery in patients with severe aortic stenosis: time to revise the
      guidelines?

PMID- 24658767
TI  - Carbamylated low-density lipoprotein induces endothelial dysfunction.
AB  - AIMS: Cardiovascular events remain the leading cause of death in Western world.
      Atherosclerosis is the most common underlying complication driven by low-density
      lipoproteins (LDL) disturbing vascular integrity. Carbamylation of lysine
      residues, occurring primarily in the presence of chronic kidney disease (CKD),
      may affect functional properties of lipoproteins; however, its effect on
      endothelial function is unknown. METHODS AND RESULTS: Low-density lipoprotein
      from healthy donors was isolated and carbamylated. Vascular reactivity after
      treatment with native LDL (nLDL) or carbamylated LDL (cLDL) was examined in organ
      chambers for isometric tension recording using aortic rings of wild-type or
      lectin-like-oxidized LDL receptor-1 (LOX-1) transgenic mice. Reactive oxygen
      species (ROS) and nitric oxide (NO) production were determined using electron
      spin resonance spectroscopy. The effect of LDL-carbamyl-lysine levels on
      cardiovascular outcomes was determined in patients with CKD during a median
      follow-up of 4.7 years. Carbamylated LDL impaired endothelium-dependent
      relaxation to acetylcholine or calcium-ionophore A23187, but not endothelium
      independent relaxation to sodium nitroprusside. In contrast, nLDL had no effect.
      Carbamylated LDL enhanced aortic ROS production by activating NADPH-oxidase.
      Carbamylated LDL stimulated endothelial NO synthase (eNOS) uncoupling at least
      partially by promoting S-glutathionylation of eNOS. Carbamylated LDL-induced
      endothelial dysfunction was enhanced in LOX-1 transgenic mice. In patients with
      CKD, LDL-carbamyl-lysine levels were significant predictors for cardiovascular
      events and all-cause mortality. CONCLUSIONS: Carbamylation of LDL induces
      endothelial dysfunction via LOX-1 activation and increased ROS production leading
      to eNOS uncoupling. This indicates a novel mechanism in the pathogenesis of
      atherosclerotic disease which may be pathogenic and prognostic in patients with
      CKD and high plasma levels of cLDL.

PMID- 24658770
TI  - High-sensitivity C-reactive protein: still need for next-generation biomarkers
      for remote future cardiovascular events.

PMID- 24658769
TI  - Management of major bleeding events in patients treated with rivaroxaban vs.
      warfarin: results from the ROCKET AF trial.
AB  - AIMS: There are no data regarding management and outcomes of major bleeding
      events in patients treated with oral factor Xa inhibitors. METHODS AND RESULTS:
      Using data from ROCKET AF, we analysed the management and outcomes of major
      bleeding overall and according to the randomized treatment. During a median
      follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate
      of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395
      rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red
      blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4)
      units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or
      cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was
      significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after
      adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001].
      Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban
      arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non
      central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95%
      CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69,
      95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin
      (interaction P = 0.51 and 0.11). CONCLUSION: Among high-risk patients with atrial
      fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC
      was less among those allocated rivaroxaban compared with warfarin. However, use
      of PRBCs and outcomes after bleeding were similar among patients randomized to
      rivaroxaban or to warfarin.

PMID- 24658771
TI  - Phage-based detection of bacterial pathogens.
AB  - Bacterial pathogens cause significant morbidity and mortality annually to both
      humans and animals. With the rampant spread of drug resistance and the
      diminishing effectiveness of current antibiotics, there is a pressing need for
      effective diagnostics for detection of bacterial pathogens and their drug
      resistances. Bacteriophages offer several unique opportunities for bacterial
      detection. This review highlights the means by which bacteriophages have been
      utilized to achieve and facilitate specific bacterial detection. 

PMID- 24658772
TI  - Glucocorticoid induced osteoblast apoptosis by increasing E4BP4 expression via up
      regulation of Bim.
AB  - It is well known that glucocorticoid (GC)-induced bone loss is caused primarily
      by hypofunction and apoptosis of osteoblasts. However, the precise molecular
      events underlying the effect of GC on osteoblast apoptosis are not fully
      understood. Recent studies implicated an important role of E4BP4 in the
      regulation of osteoblast apoptosis and differentiation. Furthermore, E4BP4 is a
      GC-regulated gene required for GC-induced apoptosis in many cells. Therefore, we
      hypothesize that E4BP4 may be implicated in the process of GC-induced osteoblast
      apoptosis. Western blot, reverse-transcription-PCR, flow cytometry, and Hoechst
      33258 staining were employed to investigate the role of E4BP4 in dexamethasone
      (DEX)-induced osteoblast apoptosis. We found that the expression of E4BP4 is
      significantly up-regulated in osteoblasts exposed to DEX. Furthermore, the
      depletion of E4BP4 significantly decreased DEX-induced osteoblast apoptosis. In
      addition, E4BP4 plays a crucial role in GC-evoked apoptosis of osteoblasts by
      enabling induction of Bim. On the basis of these results above, we can draw the
      conclusion that E4BP4 may contribute to the process of DEX-induced osteoblast
      apoptosis.

PMID- 24658773
TI  - Pulmonary sequestration: a (131)I whole body scintigraphy false-positive result.
AB  - A 35-year-old woman affected by a well-differentiated papillary thyroid carcinoma
      was referred to our hospital to perform a (131)Iodine ((131)I) whole body
      scintigraphy for restaging purpose. The patient had been previously treated with
      total thyroidectomy and three subsequent doses of (131)I for the ablation of a
      remnant jugular tissue and a suspected metastatic focus at the superior left hemi
      thorax. In spite of the previous treatments with (131)I, planar and tomographic
      images showed the persistence of an area of increased uptake at the superior left
      hemi-thorax. This finding prompted the surgical resection of the lesion.
      Histological examination of the surgical specimen showed the presence of a
      pulmonary tissue consistent with pulmonary sequestration. Even though rare,
      pulmonary sequestration should be included in the potential causes of false
      positive results of radioiodine scans.

PMID- 24658774
TI  - The 2010 Deepwater Horizon oil spill: the trauma signature of an ecological
      disaster.
AB  - The 2010 Deepwater Horizon "British Petroleum (BP)" oil spill was a mega-disaster
      characterized as the petroleum industry's largest-volume marine oil spill in
      history. Following a "wellhead blowout" that destroyed the drilling platform, 4.9
      million barrels of petroleum flowed into the Gulf of Mexico over 87 days and the
      spill expanded to cover 68,000 square miles of sea surface. However, despite the
      expansive scope of the event, systematic surveys of affected coastal populations
      found only modest effects on mental health and substance abuse. An established
      trauma signature (TSIG) methodology was used to examine the psychological
      consequences in relation to exposure to the unique constellation of hazards
      associated with the spill. A hazard profile, a matrix of psychological stressors,
      and a "trauma signature" summary for the affected Gulf Coast population--in terms
      of exposure to hazard, loss, and change--were created specifically for this human
      generated ecological disaster. Psychological risk characteristics of this event
      included: human causation featuring corporate culpability, large spill volume,
      protracted duration, coastal contamination from petroleum products, severe
      ecological damage, disruption of Gulf Coast industries and tourism, and extensive
      media coverage. The multiple impact effect was notable due to prior exposure of
      the region to Hurricane Katrina. These stressors were counterbalanced by the
      relative absence of other prominent risks for distress and psychopathology.
      Coastal residents did not experience significant onshore spill-related mortality
      or severe injury, shortages of survival needs, disruption of vital services
      (health care, schools, utilities, communications, and transportation), loss of
      homes, population displacement, destruction of the built environment, or loss of
      social supports. Initial acute economic losses were partially offset by large-sum
      BP payments for cleanup and recovery of the coastal economy. Not only did Gulf
      Coast populations display remarkable resilience in the face of daunting
      challenges, the behavioral health impact of the Deepwater Horizon spill appears
      to have been blunted by the absence of major evidence-based risks for
      psychological distress and disorder, the exemplary response, and the infusion of
      economic resources.

PMID- 24658775
TI  - Photobiological effect of low-level laser irradiation in bovine embryo production
      system.
AB  - The objectives of this study were to evaluate the effect of low-level laser
      irradiation (LLLI) on bovine oocyte and granulosa cells metabolism during in
      vitro maturation (IVM) and further embryo development. Cumulus-oocytes complexes
      (COCs) were subjected (experimental group) or not (control group) to irradiation
      with LLLI in a 633-nm wavelength and 1  J/cm2 fluency. The COCs were evaluated
      after 30 min, 8, 16, and 24 h of IVM. Cumulus cells were evaluated for cell cycle
      status, mitochondrial activity, and viability (flow cytometry). Oocytes were
      assessed for meiotic progression status (nuclear staining), cell cycle genes
      content [real-time polymerase chain reaction (PCR)], and signal transduction
      status (western blot). The COCs were also in vitro fertilized, and the cleavage
      and blastocyst rates were assessed. Comparisons among groups were statistically
      performed with 5% significance level. For cumulus cells, a significant increase
      in mitochondrial membrane potential and the number of cells progressing through
      the cycle could be observed. Significant increases on cyclin B and cyclin
      dependent kinase (CDK4) levels were also observed. Concerning the oocytes, a
      significantly higher amount of total mitogen-activated protein kinase was found
      after 8 h of irradiation, followed by a decrease in all cell cycle genes
      transcripts, exception made for the CDK4. However, no differences were observed
      in meiotic progression or embryo production. In conclusion, LLLI is an efficient
      tool to modulate the granulosa cells and oocyte metabolism.

PMID- 24658776
TI  - Porcine skin damage thresholds for 0.6 to 9.5 cm beam diameters from 1070-nm
      continuous-wave infrared laser radiation.
AB  - There is an increasing use of high-power fiber lasers in manufacturing and
      telecommunications industries operating in the infrared spectrum between 1000 and
      2000 nm, which are advertised to provide as much as 10 kW continuous output power
      at 1070 nm. Safety standards have traditionally been based on experimental and
      modeling investigations with scant data available for these wavelengths. A series
      of studies using 1070-nm infrared lasers to determine the minimum visible lesion
      damage thresholds in skin using the Yucatan miniature pig (Sus scrofa domestica)
      for a range of beam diameters (0.6, 1.1, 1.9, 2.4, 4.7, and 9.5 cm) and a range
      of exposure durations (10 ms to 10 s) is presented. Experimental peak
      temperatures associated with each damage threshold were measured using thermal
      imaging. Peak temperatures at damage threshold for the 10-s exposures were ~10
      degrees C lower than those at shorter exposures. The lowest and highest
      experimental minimum visible lesion damage thresholds were found to have peak
      radiant exposures of 19 and 432  J/cm2 for the beam diameter-exposure duration
      pairs of 2.4 cm, 25 ms and 0.6 cm, 10 s, respectively. Thresholds for beam
      diameters >2.5  cm had a weak to no effect on threshold radiant exposure levels
      for exposure times <=0.25  s, but may have a larger effect on thresholds for
      exposures >=10  s.

PMID- 24658778
TI  - Incoherence-based optimal selection of independent measurements in diffuse
      optical tomography.
AB  - An optimal measurement selection strategy based on incoherence among rows
      (corresponding to measurements) of the sensitivity (or weight) matrix for the
      near infrared diffuse optical tomography is proposed. As incoherence among the
      measurements can be seen as providing maximum independent information into the
      estimation of optical properties, this provides high level of optimization
      required for knowing the independency of a particular measurement on its
      counterparts. The proposed method was compared with the recently established data
      resolution matrix-based approach for optimal choice of independent measurements
      and shown, using simulated and experimental gelatin phantom data sets, to be
      superior as it does not require an optimal regularization parameter for providing
      the same information.

PMID- 24658777
TI  - High-speed multispectral confocal biomedical imaging.
AB  - A new approach for generating high-speed multispectral confocal images has been
      developed. The central concept is that spectra can be acquired for each pixel in
      a confocal spatial scan by using a fast spectrometer based on optical fiber delay
      lines. This approach merges fast spectroscopy with standard spatial scanning to
      create datacubes in real time. The spectrometer is based on a serial array of
      reflecting spectral elements, delay lines between these elements, and a single
      element detector. The spatial, spectral, and temporal resolution of the
      instrument is described and illustrated by multispectral images of laser-induced
      autofluorescence in biological tissues.

PMID- 24658779
TI  - Foveola nonpeeling internal limiting membrane surgery to prevent inner retinal
      damages in early stage 2 idiopathic macula hole.
AB  - PURPOSE: The purpose of this study was to investigate and present the results of
      a new vitrectomy technique to preserve the foveolar internal limiting membrane
      (ILM) during ILM peeling in early stage 2 macular holes (MH). METHODS: The
      medical records of 28 consecutive patients (28 eyes) with early stage 2 MH were
      retrospectively reviewed and randomly divided into two groups by the extent of
      ILM peeing. Group 1: foveolar ILM nonpeeling group (14 eyes), and group 2: total
      peeling of foveal ILM group (14 eyes). A donut-shaped ILM was peeled off, leaving
      a 400-MUm-diameter ILM over foveola in group 1. RESULTS: Smooth and symmetric
      umbo foveolar contour was restored without inner retinal dimpling in all eyes in
      group 1, but not in group 2. The final vision was better in group 1 (P = 0.011).
      All eyes in group 1 (100 %) and seven of 14 eyes in group 2 (50 %)regained the
      inner segment/outer segment (IS/OS) line. Restoration of the umbo light reflex
      was found in 12 of 14 eyes in group 1 (86 %) but none in group 2 (0 %).
      CONCLUSIONS: Nonpeeling of the foveolar ILM in early stage 2 idiopathic MH
      surgery prevented inner retinal damages, restored umbo light reflex, achieved
      better foveolar microstructures, and led to better final visual acuity.

PMID- 24658780
TI  - Genetic structure and molecular variability of potato virus M populations.
AB  - To investigate the genetic diversity of potato virus M (PVM; genus Carlavirus,
      family Betaflexiviridae), the complete nucleotide sequence of the coat protein
      gene of 30 PVM isolates from a major potato-growing region in Iran were
      determined. Phylogenetic analysis of these Iranian PVM isolates together with
      those available in the GenBank database suggested two divergent evolutionary
      lineages that did not reflect the origin of the isolates, and these were
      designated as PVM-o and PVM-d. Examination of the genetic variability of the coat
      protein of Iranian isolates and their counterparts whose sequences are available
      in the Genbank database revealed 16 genotype groups in the PVM population.
      Analysis of the synonymous-tononsynonymous ratio showed strong purifying
      selection in the CP gene in the genotype groups of divergent clades.

PMID- 24658781
TI  - Establishment of three new genera in the family Geminiviridae: Becurtovirus,
      Eragrovirus and Turncurtovirus.
AB  - The family Geminiviridae includes plant-infecting circular single-stranded DNA
      viruses that have geminate particle morphology. Members of this family infect
      both monocotyledonous and dicotyledonous plants and have a nearly global
      distribution. With the advent of new molecular tools and low-cost sequencing,
      there has been a significant increase in the discovery of new geminiviruses in
      various cultivated and non-cultivated plants. In this communication, we highlight
      the establishment of three new genera (Becurtovirus, Eragrovirus and
      Turncurtovirus) to accommodate various recently discovered geminiviruses that are
      highly divergent and, in some cases, have unique genome architectures. The genus
      Becurtovirus has two viral species, Beet curly top Iran virus (28 isolates;
      leafhopper vector Circulifer haematoceps) and Spinach curly top Arizona virus (1
      isolate; unknown vector), whereas the genera Eragrovirus and Turncurtovirus each
      have a single assigned species: Eragrostis curvula streak virus (6 isolates;
      unknown vector) and Turnip curly top virus (20 isolates; leafhopper vector
      Circulifer haematoceps), respectively. Based on analysis of all of the genome
      sequences available in public databases for each of the three new genera, we
      provide guidelines and protocols for species and strain classification within
      these three new genera. 

PMID- 24658782
TI  - White spot syndrome virus (WSSV) infection in shrimp (Litopenaeus vannamei)
      exposed to low and high salinity.
AB  - White spot syndrome virus (WSSV) has a worldwide distribution and is considered
      one of the most pathogenic and devastating viruses to the shrimp industry. A few
      studies have explored the effect of WSSV on shrimp acclimated to low (5 practical
      salinity units [psu]) or high ([40 psu) salinity conditions. In this work, we
      analysed the physiological response of WSSV-infected Litopenaeus vannamei
      juveniles that were acclimated to different salinities (5, 15, 28, 34 and 54
      psu). We evaluated the osmotic response and survival of the shrimp at different
      times after infection (0 to 48 hours), and we followed the expression levels of a
      viral gene (vp664) in shrimp haemolymph using real-time PCR. Our results indicate
      that the susceptibility of the shrimp to the virus increased at extreme
      salinities (5 and 54 psu), with higher survival rates at 15 and 28 psu, which
      were closer to the iso-osmotic point (24.7 psu, 727.5 mOsmol/kg). Acute exposure
      to the virus made the haemolymph less hyperosmotic at 5 and 15 psu and less hypo
      osmotic at higher salinities ([28 psu). The capacity of white shrimp to
      osmoregulate, and thus survive, significantly decreased following WSSV infection.
      According to our results, extreme salinities (5 or 54 psu) are more harmful than
      seawater.

PMID- 24658783
TI  - Anisotropic charge transport in large single crystals of pi-conjugated organic
      molecules.
AB  - The electronic properties of organic semiconductors depend strongly on the nature
      of the molecules, their conjugation and conformation, their mutual distance and
      the orientation between adjacent molecules. Variations of intramolecular
      distances and conformation disturb the conjugation and perturb the delocalization
      of charges. As a result, the mobility considerably decreases compared to that of
      a covalently well-organized crystal. Here, we present electrical characterization
      of large single crystals made of the regioregular octamer of 3-hexyl-thiophene
      (3HT)8 using a conductive-atomic force microscope (C-AFM) in air. We find a large
      anisotropy in the conduction with charge mobility values depending on the
      crystallographic orientation of the single crystal. The smaller conduction is in
      the direction of pi-pi stacking (along the long axis of the single crystal) with
      a mobility value in the order of 10(-3) cm(2) V(-1) s(-1), and the larger one is
      along the molecular axis (in the direction normal to the single crystal surface)
      with a mobility value in the order of 0.5 cm(2) V(-1) s(-1). The measured current
      voltage (I-V) curves showed that along the molecular axis, the current followed
      an exponential dependence corresponding to an injection mode. In the pi-pi
      stacking direction, the current exhibits a space charge limited current (SCLC)
      behavior, which allows us to estimate the charge carrier mobility. 

PMID- 24658784
TI  - A method of 'speed coefficients' for biochemical model  reduction applied to the
      NF-kappaB system.
AB  - The relationship between components of biochemical network and the resulting
      dynamics of the overall system is a key focus of computational biology. However,
      as these networks and resulting mathematical models are inherently complex and
      non-linear, the understanding of this relationship becomes challenging. Among
      many approaches, model reduction methods provide an avenue to extract components
      responsible for the key dynamical features of the system. Unfortunately, these
      approaches often require intuition to apply. In this manuscript we propose a
      practical algorithm for the reduction of biochemical reaction systems using fast
      slow asymptotics. This method allows the ranking of system variables according to
      how quickly they approach their momentary steady state, thus selecting the
      fastest for a steady state approximation. We applied this method to derive models
      of the Nuclear Factor kappa B network, a key regulator of the immune response
      that exhibits oscillatory dynamics. Analyses with respect to two specific
      solutions, which corresponded to different experimental conditions identified
      different components of the system that were responsible for the respective
      dynamics. This is an important demonstration of how reduction methods that
      provide approximations around a specific steady state, could be utilised in order
      to gain a better understanding of network topology in a broader context.

PMID- 24658788
TI  - [Multimorbidity: a central challenge for modern medicine].

PMID- 24658785
TI  - The IclR-family regulator BapR controls biofilm formation in B. cenocepacia H111.
AB  - In Burkholderia cenocepacia H111, the large surface protein BapA plays a crucial
      role in the formation of highly structured communities, known as biofilms. We
      have recently demonstrated that quorum sensing (QS) is necessary for the maximal
      expression of bapA. In this study we identify BapR, a protein from the IclR
      family of transcriptional regulators that, in conjunction with QS, controls
      biofilm formation by affecting the expression of bapA. We present evidence that,
      in addition to bapA, BapR influences the expression of extracellular proteases,
      swimming motility and has a profound impact in the incidence of persister cells,
      making this regulator an interesting target for persister cells and biofilm
      eradication. 

PMID- 24658789
TI  - [Fiber optic endoscopic evaluation of swallowing on the stroke unit].

PMID- 24658790
TI  - Serum 25 hydroxyvitamin D in employees of a Middle Eastern university hospital.
AB  - BACKGROUND: The Middle East registers the highest rate of vitamin D deficiency
      worldwide. In Lebanon, previous studies looked at this deficiency in
      schoolchildren, university students, young adults and postmenopausal women.
      However, no previous study was performed in hospital workers. The objective of
      our study was to evaluate vitamin D status in a Beirut hospital center and to
      look at the potential factors influencing these measurements. METHODS: This cross
      sectional study was performed on hospital employees who came for a regular
      checkup at the primary health-care department. 25(OH)D measurements were
      performed using the Dia-Sorin chemiluminescent assay. RESULTS: 392 subjects (318
      women and 74 men) were included in the study. The mean age of the participants
      was 41.02 +/- 11.3 years. The mean 25(OH)D level was 15.61 +/- 7.91 ng/ml, with
      no significant difference according to gender. There were no significant
      correlations between 25(OH)D and both BMI and age, but 25(OH)D was significantly
      associated with educational level (p = 0.03). There was a significant difference
      in 25(OH)D levels according to season (p < 0.001) and a significant association
      between 25(OH)D and the reported weekly hours of sun exposure (r = 0.1, p =
      0.032), but not with the reported sunscreen use. Fish consumption was positively
      associated with 25(OH)D levels (p = 0.018), while milk, dairy product or egg
      consumption did not achieve any significant relationship. In a stepwise linear
      regression analysis, fish consumption and season were the only independent
      predictors of 25(OH)D levels (p = 0.007 and p = 0.0001 respectively). CONCLUSION:
      Vitamin D deficiency is common among hospital workers. This finding reinforces
      the need for vitamin D supplementation in these high-risk populations.

PMID- 24658791
TI  - The "slower" the better.

PMID- 24658792
TI  - Rapid sealing and cutting of porcine blood vessels, ex vivo, using a high-power,
      1470-nm diode laser.
AB  - Suture ligation with subsequent cutting of blood vessels to maintain hemostasis
      during surgery is time consuming and skill intensive. Energy-based
      electrosurgical and ultrasonic devices are often used to replace sutures and
      mechanical clips to provide rapid hemostasis and decrease surgery time. Some of
      these devices may create undesirably large collateral zones of thermal damage and
      tissue necrosis, or require separate mechanical blades for cutting. Infrared
      lasers are currently being explored as alternative energy sources for vessel
      sealing applications. In a previous study, a 1470-nm laser was used to seal
      vessels 1 to 6 mm in diameter in 5 s, yielding burst pressures of ~500  mmHg. The
      purpose of this study was to provide vessel sealing times comparable with current
      energy-based devices, incorporate transection of sealed vessels, and demonstrate
      high vessel burst pressures to provide a safety margin for future clinical use. A
      110-W, 1470-nm laser beam was transmitted through a fiber and beam shaping
      optics, producing a 90-W linear beam 3.0 by 9.5 mm for sealing (400  W/cm2), and
      1.1 by 9.6 mm for cutting (1080  W/cm2). A two-step process sealed and then
      transected ex vivo porcine renal vessels (1.5 to 8.5 mm diameter) in a bench top
      setup. Seal and cut times were 1.0 s each. A burst pressure system measured seal
      strength, and histologic measurements of lateral thermal spread were also
      recorded. All blood vessels tested (n=55 seal samples) were sealed and cut, with
      total irradiation times of 2.0 s and mean burst pressures of 1305+/-783  mmHg.
      Additional unburst vessels were processed for histological analysis, showing a
      lateral thermal spread of 0.94+/-0.48  mm (n=14 seal samples). This study
      demonstrated that an optical-based system is capable of precisely sealing and
      cutting a wide range of porcine renal vessel sizes and, with further development,
      may provide an alternative to radiofrequency- and ultrasonic-based vessel sealing
      devices.

PMID- 24658793
TI  - Bionanocomposites based on layered silicates and cationic starch as eco-friendly
      adsorbents for hexavalent chromium removal.
AB  - Functional bionanocomposites based on two layered silicates, the commercial
      montmorillonite known as Cloisite(r)Na and a natural bentonite from Algeria, were
      prepared by intercalation of cationic starch, synthesized with two different
      degrees of substitution, 0.85 and 0.55. After characterization of the prepared
      bionanocomposites by XRD and zeta potential measurements, batch studies were
      conducted to evaluate the adsorption capacity of hexavalent chromium anions from
      aqueous solution. The adsorption isotherms, adsorption kinetics, and the effect
      of pH on the process were studied. The removal efficiency was evaluated in the
      presence of competing anions such as NO3(-), ClO4(-), SO4(2-) and Cl(-). In order
      to regenerate the adsorbent for its repeated use, the regeneration process was
      studied in two different extractant solutions, 0.1 M NaCl at pH 10 and 0.28 M
      Na2CO3 at pH 12. 

PMID- 24658794
TI  - Viability characterization of Taxus chinensis plant cell suspension  cultures by
      rapid colorimetric- and image analysis-based  techniques.
AB  - For the commercially established process of paclitaxel production with Taxus
      chinensis plant cell culture, the size of plant cell aggregates and phenotypic
      changes in coloration during cultivation have long been acknowledged as
      intangible parameters. So far, the variability of aggregates and coloration of
      cells are challenging parameters for any viability assay. The aim of this study
      was to investigate simple and non-toxic methods for viability determination of
      Taxus cultures in order to provide a practicable, rapid, robust and reproducible
      way to sample large amounts of material. A further goal was to examine whether
      Taxus aggregate cell coloration is related to general cell viability and might be
      exploited by microscopy and image analysis to gain easy access to general cell
      viability. The Alamar Blue assay was found to be exceptionally eligible for
      viability estimation. Moreover, aggregate coloration, as a morphologic attribute,
      was quantified by image analysis and found to be a good and traceable indicator
      of T. chinensis viability.

PMID- 24658795
TI  - Modeling of an aerobic bioprocess based on gas exchange  and dynamics: a novel
      approach.
AB  - Monitoring of the biological degradation of a substrate by microorganisms is a
      key issue, especially in the soil bioremediation area. Respiration measurement is
      the easiest way to obtain online information on the biological activity.
      Nevertheless, it is indirectly related to substrate consumption and microbial
      growth. To be able to link these phenomena, a robust and descriptive model has
      been developed. Both biological and gas/liquid transfer dynamics must be taken
      into account to link the online measurement with the actual biological
      respiration. For that, experimental evolution of the respiratory ouotient (RQ)
      during a biodegradation has been compared against general biodegradation
      knowledge. To obtain a reliable model, practical and structural sensitivity
      analyses have been conducted. The model can describe the evolution of both online
      measurable and non-measurable states. It also gives a new definition of the
      apparent RQ, measured in the gas phase, compared to the actual biological RQ.

PMID- 24658796
TI  - Modeling the microbial growth and temperature profile in a fixed-bed bioreactor.
AB  - Aiming to scale up and apply control and optimization strategies, currently is
      required the development of accurate plant models to forecast the process
      nonlinear dynamics. In this work, a mathematical model to predict the growth of
      the Kluyveromyces marxianus and temperature profile in a fixed-bed bioreactor for
      solid-state fermentation using sugarcane bagasse as substrate was built up. A
      parameter estimation technique was performed to fit the mathematical model to the
      experimental data. The estimated parameters and the model fitness were evaluated
      with statistical analyses. The results have shown the estimated parameters
      significance, with 95 % confidence intervals, and the good quality of process
      model to reproduce the experimental data. 

PMID- 24658797
TI  - Influence of the shear stress and salinity on Anammox biofilms formation:
      modelling results.
AB  - Anammox biomass has a long duplication time and low yield, thus the process must
      be operated in reactors with good sludge retention, such as biofilm systems.
      Therefore, it would be important to research the ability of Anammox biomass to
      form biofilms under different conditions. The effects of shear stress and
      salinity (NaCl and CaCl2) on Anammox biofilm formation were studied. Anammox
      bacteria showed good attachment capacity, with an initial adhesion phase lasting
      for 5-7 days at the different flow rates tested (Reynolds numbers 54, 63, 188 and
      400). A four-parameter model was developed and the experimental data fitted well
      into the model. The presence of 5 g/L of each of the two salts favoured the
      formation of Anammox biofilm. The effects of CaCl2 were stronger than those
      caused by NaCl. 15 g/L of NaCl was detrimental for the biofilm, probably due to
      an inhibitory effect. 

PMID- 24658798
TI  - Energetics of intermolecular hydrogen bonds in a hydrophobic protein cavity.
AB  - This work explores the energetics of intermolecular H-bonds inside a hydrophobic
      protein cavity. Kinetic measurements were performed on the gaseous deprotonated
      ions (at the -7 charge state) of complexes of bovine beta-lactoglobulin (Lg) and
      three monohydroxylated analogs of palmitic acid (PA): 3-hydroxypalmitic acid (3
      OHPA), 7-hydroxypalmitic acid (7-OHPA), and 16-hydroxypalmitic acid (16-OHPA).
      From the increase in the activation energy for the dissociation of the (Lg + X
      OHPA)7- ions, compared with that of the (Lg + PA)7- ion, it is concluded that the
      -OH groups of the X-OHPA ligands participate in strong (5-11 kcal mol-1)
      intermolecular H-bonds in the hydrophobic cavity of Lg. The results of molecular
      dynamics (MD) simulations suggest that the -OH groups of 3-OHPA and 16-OHPA act
      as H-bond donors and interact with backbone carbonyl oxygens, whereas the -OH
      group of 7-OHPA acts as both H-bond donor and acceptor with nearby side chains.
      The capacity for intermolecular H-bonds within the Lg cavity, as suggested by the
      gas-phase measurements, does not necessarily lead to enhanced binding in aqueous
      solution. The association constant (Ka) measured for 7-OHPA [(2.3 +/- 0.2) * 105
      M-1] is similar to the value for the PA [(3.8 +/- 0.1) * 105 M-1]; Ka for 3-OHPA
      [(1.1 +/- 0.3) * 106 M-1] is approximately three-times larger, whereas Ka for 16
      OHPA [(2.3 +/- 0.2) * 104 M-1] is an order of magnitude smaller. Taken together,
      the results of this study suggest that the energetic penalty to desolvating the
      ligand -OH groups, which is necessary for complex formation, is similar in
      magnitude to the energetic contribution of the intermolecular H-bonds.

PMID- 24658799
TI  - Solution dependence of the collisional activation of ubiquitin [M + 7H](7+) ions.
AB  - The solution dependence of gas-phase unfolding for ubiquitin [M + 7H](7+) ions
      has been studied by ion mobility spectrometry-mass spectrometry (IMS-MS).
      Different acidic water:methanol solutions are used to favor the native (N), more
      helical (A), or unfolded (U) solution states of ubiquitin. Unfolding of gas-phase
      ubiquitin ions is achieved by collisional heating and newly formed structures are
      examined by IMS. With an activation voltage of 100 V, a selected distribution of
      compact structures unfolds, forming three resolvable elongated states (E1-E3).
      The relative populations of these elongated structures depend strongly on the
      solution composition. Activation of compact ions from aqueous solutions known to
      favor N-state ubiquitin produces mostly the E1 type elongated state, whereas
      activation of compact ions from methanol containing solutions that populate A
      state ubiquitin favors the E3 elongated state. Presumably, this difference arises
      because of differences in precursor ion structures emerging from solution. Thus,
      it appears that information about solution populations can be retained after
      ionization, selection, and activation to produce the elongated states. These data
      as well as others are discussed.

PMID- 24658800
TI  - Mass spectrometry combinations for structural characterization of sulfated
      steroid metabolites.
AB  - Steroid conjugates, which often occur as metabolites, are challenging to
      characterize. One application is female-mouse urine, where steroid conjugates
      serve as important ligands for the pheromone-sensing neurons. Although the two
      with the highest abundance in mouse urine were previously characterized with mass
      spectrometry (MS) and NMR to be sulfated steroids, many more exist but remain
      structurally unresolved. Given that their physical and chemical properties are
      similar, they are likely to have a sulfated steroid ring structure. Because these
      compounds occur in trace amounts in mouse urine and elsewhere, their
      characterization by NMR will be difficult. Thus, MS methods become the primary
      approach for determining structure. Here, we show that a combination of MS tools
      is effective for determining the structures of sulfated steroids. Using 4
      pregnene analogs, we explored high-resolving power MS (HR-MS) to determine
      chemical formulae; HD exchange MS (HDX-MS) to determine number of active,
      exchangeable hydrogens (e.g., OH groups); methoxyamine hydrochloride (MOX)
      derivatization MS, or reactive desorption electrospray ionization with
      hydroxylamine to determine the number of carbonyl groups; and tandem MS (MS(n)),
      high-resolution tandem MS (HRMS/MS), and GC-MS to obtain structural details of
      the steroid ring. From the fragmentation studies, we deduced three major
      fragmentation rules for this class of sulfated steroids. We also show that a
      combined MS approach is effective for determining structure of steroid
      metabolites, with important implications for targeted metabolomics in general and
      for the study of mouse social communication in particular.

PMID- 24658801
TI  - Fluorine bonding enhances the energetics of protein-lipid binding in the gas
      phase.
AB  - This paper reports on the first experimental study of the energies of noncovalent
      fluorine bonding in a protein-ligand complex in the absence of solvent. Arrhenius
      parameters were measured for the dissociation of gaseous deprotonated ions of
      complexes of bovine beta-lactoglobulin (Lg), a model lipid-binding protein, and
      four fluorinated analogs of stearic acid (SA), which contained (X =) 13, 15, 17,
      or 21 fluorine atoms. In all cases, the activation energies (E(a)) measured for
      the loss of neutral XF-SA from the (Lg + XF-SA)7- ions are larger than for SA.
      From the kinetic data, the average contribution of each > CF2 group to E(a) was
      found to be ~1.1 kcal mol-1, which is larger than the ~0.8 kcal mol-1 value
      reported for > CH2 groups. Based on these results, it is proposed that
      fluorocarbon-protein interactions are inherently stronger (enthalpically) than
      the corresponding hydrocarbon interactions.

PMID- 24658802
TI  - Numerical modeling of ion transport in an ESI-MS system.
AB  - Gas and ion transport in the capillary-skimmer subatmospheric interface of a mass
      spectrometer, which is typically utilized to separate unevaporated micro-droplets
      from ions, was studied numerically using a two-step approach spanning multiple
      gas dynamic regimes. The gas flow in the heated capillary and in the interface
      was determined by solving numerically the Navier-Stokes equation. The capillary
      to-skimmer gas/ion flow was modeled through the solution of the full Boltzmann
      equation with a force term. The force term, together with calculated aerodynamic
      drag, determined the ion motion in the gap between the capillary and skimmer.
      Three-dimensional modeling of the impact of the voltage applied to the Einzel
      lens on the transmission of doubly charged peptide ions through the skimmer
      orifice was compared with experimental data obtained in the companion study. Good
      agreement between measured and computed signals was observed. The numerical
      results indicate that as many as 75% of the ions that exit from the capillary are
      lost on the conical surface of the skimmer or capillary outer surface because of
      the electrostatic force and plume divergence.

PMID- 24658803
TI  - Time-resolved imaging of the MALDI linear-TOF ion cloud: direct visualization and
      exploitation of ion optical phenomena using a position- and time-sensitive
      detector.
AB  - In this study, we describe the implementation of a position- and time-sensitive
      detection system (Timepix detector) to directly visualize the spatial
      distributions of the matrix-assisted laser desorption ionization ion cloud in a
      linear-time-of-flight (MALDI linear-ToF) as it is projected onto the detector
      surface. These time-resolved images allow direct visualization of m/z-dependent
      ion focusing effects that occur within the ion source of the instrument. The
      influence of key parameters, namely extraction voltage (E(V)), pulsed-ion
      extraction (PIE) delay, and even the matrix-dependent initial ion velocity was
      investigated and were found to alter the focusing properties of the ion-optical
      system. Under certain conditions where the spatial focal plane coincides with the
      detector plane, so-called x-y space focusing could be observed (i.e., the
      focusing of the ion cloud to a small, well-defined spot on the detector). Such
      conditions allow for the stigmatic ion imaging of intact proteins for the first
      time on a commercial linear ToF-MS system. In combination with the ion-optical
      magnification of the system (~100*), a spatial resolving power of 11-16 MUm with
      a pixel size of 550 nm was recorded within a laser spot diameter of ~125 MUm.
      This study demonstrates both the diagnostic and analytical advantages offered by
      the Timepix detector in ToF-MS.

PMID- 24658804
TI  - Measurement and visualization of mass transport for the flowing atmospheric
      pressure afterglow (FAPA) ambient mass-spectrometry source.
AB  - Ambient desorption/ionization mass spectrometry (ADI-MS) has developed into an
      important analytical field over the last 9 years. The ability to analyze samples
      under ambient conditions while retaining the sensitivity and specificity of mass
      spectrometry has led to numerous applications and a corresponding jump in the
      popularity of this field. Despite the great potential of ADI-MS, problems remain
      in the areas of ion identification and quantification. Difficulties with ion
      identification can be solved through modified instrumentation, including accurate
      mass or MS/MS capabilities for analyte identification. More difficult problems
      include quantification because of the ambient nature of the sampling process. To
      characterize and improve sample volatilization, ionization, and introduction into
      the mass spectrometer interface, a method of visualizing mass transport into the
      mass spectrometer is needed. Schlieren imaging is a well-established technique
      that renders small changes in refractive index visible. Here, schlieren imaging
      was used to visualize helium flow from a plasma-based ADI-MS source into a mass
      spectrometer while ion signals were recorded. Optimal sample positions for
      melting-point capillary and transmission-mode (stainless steel mesh) introduction
      were found to be near (within 1 mm of) the mass spectrometer inlet. Additionally,
      the orientation of the sampled surface plays a significant role. More efficient
      mass transport resulted for analyte deposits directly facing the MS inlet.
      Different surfaces (glass slide and rough surface) were also examined; for both
      it was found that the optimal position is immediately beneath the MS inlet.

PMID- 24658805
TI  - On-plate self-desalting and matrix-free LDI MS analysis of peptides with a
      surface patterned sample support.
AB  - A hydrophobic-hydrophilic-hydrophobic pattern has been produced on the surface of
      a silicon substrate for selective enrichment, self-desalting, and matrix-free
      analysis of peptides in a single step. Upon sample application, the sample
      solution is first confined in a small area by a hydrophobic F-SAM outer area,
      after which salt contaminants and peptides are selectively enriched in the
      hydrophilic and hydrophobic areas, respectively. Simultaneously, matrix
      background noise is significantly reduced or eliminated because of immobilization
      of matrix molecules. As a result, the detection sensitivity is enhanced 20-fold
      compared with that obtained using the usual MALDI plate, and interference-free
      detection is achieved in the low m/z range. In addition, peptide ions can be
      identified unambiguously in the presence of NH4HCO3 (100 mM), urea (1 M), and
      NaCl (1 M). When the device was applied to the analysis of BSA digests, the
      peptide recovery and protein identification confidence were greatly improved.

PMID- 24658806
TI  - Quantitative surface analysis of a binary drug mixture--suppression effects in
      the detection of sputtered ions and post-ionized neutrals.
AB  - A systematic mass spectrometric study of two of the most common analgesic drugs,
      paracetamol and ibuprofen, is reported. The drugs were studied by means of
      secondary ion mass spectrometry (SIMS) and secondary neutral mass spectrometry
      (SNMS) using laser post-ionization (LPI) both in pure samples and in a two
      component mixture. Ion suppression within the two-component system observed in
      SIMS mode is ameliorated using LPI under room temperature analysis. However,
      suppression effects are apparent in LPI mode on performing the analysis at
      cryogenic temperatures, which we attribute to changes in the desorption
      characteristics of sputtered molecules, which influences the subsequent post
      ionization efficiency. This suggests different mechanisms of ion suppression in
      SIMS and LPI modes.

PMID- 24658807
TI  - Evaluation of the potential of GC-APCI-MS for the analysis of pesticide residues
      in fatty matrices.
AB  - A method based on gas chromatography-atmospheric pressure chemical ionization
      mass spectrometry (GC-APCI-MS) has been developed for the analysis of pesticides
      in meat by using quadrupole-time of flight mass spectrometry (QTOF-MS).
      Ionization and MS conditions were studied for 71 compounds, although only 51
      showed acceptable performance. The protonated form of the analytes was mainly
      found ([M + H]+), although some compounds generated the molecular ion (M+(*)). A
      fast and generic extraction procedure was applied in sample pretreatment. The
      analytical method was suitable for qualitative analysis, and it was also
      evaluated for quantitative analysis, obtaining adequate recovery and precision
      values for most of the studied analytes at two concentration levels (50 and 150
      MUg/kg). Several operational drawbacks were found with this instrument, such as
      slow stabilization and moderate sensitivity, although the fast switching between
      LC and GC allows the increase of its applicability.

PMID- 24658808
TI  - Quantitative analysis of long chain fatty acids present in a Type I kerogen using
      electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry: compared with BF3/MeOH methylation/GC-FID.
AB  - Long chain fatty acids (LCFAs) are present in various natural samples and are
      easily detectable using electrospray ionization Fourier transform ion cyclotron
      resonance mass spectrometry (ESI-FT-ICR-MS) in negative ion mode. The capability
      of the ESI-FT-ICR-MS for quantifying LCFAs was evaluated by performing a standard
      addition followed by an internal standard methodology to several kerogen extracts
      using n-C20 fatty acid as standard. As the concentration of the standard
      increased, the magnitude of its peak (m/z 311.29525) increased linearly but with
      two separate slopes, leaving the entire mass spectra relatively unchanged, which
      shows evidence of reproducibility. Response factors of other LCFAs are obtained
      using a standard addition approach. We employed five LCFA standards (n-C15, n
      C19, n-C24, n-C26, and n-C30) with different carbon numbers. This allowed us to
      determine the response factor of all fatty acids (with carbon number between 15
      and 30) by plotting the slope of each standard versus its carbon number. With the
      observed response factors and use of the internal standard, the concentrations of
      LCFAs in four kerogen extracts were measured by ESI-FT-ICR-MS and compared with
      those from GC-FID. The carbon number distribution obtained by ESI-FT-ICR-MS
      matched well the GC-FID distribution (5%-50%) with the exception of C16 and C18,
      considering that ESI-FT-ICR-MS does not differentiate between normal and branched
      LCFAs, whereas GC-FID does. This allows one to quantitatively compare samples
      with a relatively similar matrix for specific compounds such as LCFAs with no
      need of time-consuming derivatization procedures. Moreover, the calibration can
      be extended to higher carbon numbers with ESI-FT-ICR-MS, beyond the capabilities
      of GC/MS.

PMID- 24658810
TI  - Frank H. Field (1922-2013).

PMID- 24658809
TI  - Novel galvanic nanostructures of Ag and Pd for efficient laser
      desorption/ionization of low molecular weight compounds.
AB  - A simple approach for synthesis of palladium and silver nanostructures with
      readily adjustable morphologies was developed using galvanic electrochemical
      deposition, for application to surface-assisted laser desorption/ionization
      (SALDI) of small biological molecules. A range of fatty acids, triglycerides,
      carbohydrates, and antibiotics were investigated to assess the performance of the
      new materials. Intense analyte cations were generated from the galvanic surfaces
      upon UV laser irradiation such as potassium adducts for a film thickness <100 nm
      (originating from impurities of the electrolyte solution) and Pd and Ag cluster
      ions for films with a thickness >120 nm. Possible laser desorption/ionization
      mechanisms of these galvanic structures are discussed. The films exhibited self
      organizing abilities and adjustable morphologies by changing electrochemical
      parameters. They did not require any stabilizing agents and were inexpensive and
      very easy to produce. SALDI analysis showed that the materials were stable under
      ambient conditions and analytical results with excellent measurement
      reproducibility and detection sensitivity similar to MALDI were obtained.
      Finally, we applied the galvanic surfaces to fast screening of natural oils with
      minimum sample preparation.

PMID- 24658811
TI  - Sarcoidosis and the occurrence of malignant diseases.
AB  - Whereas the association between sarcoidosis and malignant diseases has been well
      described, it remains controversial whether this association is merely a
      coincidence or the consequence of a common pathophysiologic mechanism. We
      investigated the incidence of malignancies in a large cohort of patients with
      sarcoidosis from a German University Hospital. Patients with a malignant disease
      were identified in a retrospective analysis of a cohort of 425 patients with
      sarcoidosis at the Medical Center of the University of Heidelberg. The type of
      malignancies and the onset before, concomitant or after sarcoidosis were
      analyzed. Sixty-one patients with a malignant disease were identified in our
      cohort of 425 patients with sarcoidosis. Among them, there were 18 patients with
      malignant lymphoma, 13 with breast cancer and 5 with cervical cancer. Malignant
      lymphoma was diagnosed up to 30 years after sarcoidosis with a median of 6.9
      years. Breast or cervical cancers were diagnosed up to 20 years before or after
      sarcoidosis, and the median was 0.0 years. A high prevalence of B-cell lymphoma,
      breast and cervical cancers was found in our sarcoidosis cohort. In most
      patients, B-cell lymphoma was diagnosed many years after chronic sarcoidosis. In
      contrast, the diagnosis of breast or cervical cancer was evenly distributed
      before, around and after the diagnosis of sarcoidosis. Our hypothesis is that the
      immune dysregulation which persists during or after chronic sarcoidosis might
      represent a contributing factor for the development of B-cell lymphoma. 

PMID- 24658812
TI  - Effectiveness of extracorporeal shock wave therapy in bone  marrow edema syndrome
      of the hip.
AB  - There is no gold standard for treatment of bone marrow edema syndrome of the hip
      (BMESH). Usually, treatment is conservative, owing to the favorable and self
      limiting prognosis. In musculoskeletal disorders, the effectiveness of
      extracorporeal shock wave therapy (ESWT) has been widely recognized and recent
      research supports its use in the treatment of the first stages of avascular
      osteonecrosis of the proximal femur and in other conditions where bone marrow
      edema is present. On this basis, we performed a prospective study to evaluate the
      effectiveness of ESWT in normalizing the symptoms and imaging features of BMESH.
      Twenty consecutive symptomatic patients underwent two treatments of high-energy
      ESWT and were followed-up at 2, 3 and 6 months, with a final clinical follow-up
      at mean 15.52 +/- 1.91 months. Patients underwent magnetic resonance imaging of
      the hip and were evaluated according to the Harris hip score. The mean
      improvement in HHS over the course of the study was of 58.5 +/- 14.9 points (p <
      0.0001), and the mean edema area reduced from 981.9 +/- 453.2 mm(2) pre-treatment
      to 107.8 +/- 248.1 mm(2) at 6 months. ESWT seems to be a powerful, non
      pharmacological tool that produces rapid pain relief and functional improvement
      and aids the normalization of the vascular and metabolic impairments which
      characterize BMESH.

PMID- 24658813
TI  - Effects of ginsenoside Re on rat jejunal contractility.
AB  - Ginsenoside Re (GRe) exerts diverse effects. Based on our observations, the
      present study was designed to investigate GRe-exerted bidirectional regulation
      (BR) on the contractility of isolated jejunal segment. Six pairs of different low
      and high contractile states of rat jejunal segment were established and used in
      the study. Stimulatory effects on the contractility of jejunal segment were
      exerted by GRe (10.0 MUM) in all 6 low contractile states, and inhibitory effects
      were exerted in all 6 high contractile states, indicating that GRe exerted BR on
      the contractility of jejunal segment. The effects of GRe on the phosphorylation
      of 20 kDa myosin light chain, protein contents of myosin light chain kinase
      (MLCK) and MLCK mRNA expression in jejunal segment in low and high contractile
      states were also bidirectional. GRe-exerted BR was abolished in the presence of
      neurotoxin tetrodotoxin or Ca2+ channel blocker verapamil or c-Kit receptor
      tyrosine kinase inhibitor imatinib. Atropine blocked the stimulatory effects of
      GRe on jejunal contractility in low-Ca2+-induced low contractile state;
      phentolamine, propranolol and l-NG-nitro-arginine blocked the inhibitory effects
      in high-Ca2+-induced high contractile state, respectively. In summary, GRe
      exerted BR depends on jejunal contractile state and requires the presence of
      enteric nervous system, Ca2+, and interstitial cells of Cajal; the stimulatory
      effects of GRe on jejunal contractility are related to cholinergic stimulation
      and inhibitory effects are related to adrenergic activation and nitric oxide
      relaxing mechanisms.

PMID- 24658814
TI  - Emerging technologies for biomedical analysis.
AB  - Options for biomedical analysis continue to evolve from many fields of study,
      employing diverse detection and quantification methods. New technologies in this
      arena focus on improving the sensitivity of analysis and the speed of testing, as
      well as producing systems at low cost which can be used on site as a point-of
      care device for telemedicine applications. In this article, the most important
      original experimental platforms as well as current commercial approaches to
      biomedical analysis are critically chosen and reviewed, covering January 2010 to
      January 2014. While literature is quite broad and numerous, there is clear
      emphasis on biological recognition and imaging for the most impactful works. The
      analytical approaches are discussed in terms of their utility in diagnostics and
      biomedical testing. 

PMID- 24658815
TI  - The clinical relevance and management of monoclonal gammopathy of undetermined
      significance and related disorders: recommendations from the European Myeloma
      Network.
AB  - Monoclonal gammopathy of undetermined significance is one of the most common pre
      malignant disorders. IgG and IgA monoclonal gammopathy of undetermined
      significance are precursor conditions of multiple myeloma; light-chain monoclonal
      gammopathy of undetermined significance of light-chain multiple myeloma; and IgM
      monoclonal gammopathy of undetermined significance of Waldenstrom's
      macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as
      determined by bone marrow plasma cell percentage or M-protein level, as well as
      biological characteristics, including heavy chain isotype and light chain
      production, are helpful in predicting risk of progression of monoclonal
      gammopathy of undetermined significance to symptomatic disease. Furthermore,
      alterations in the bone marrow microenvironment of monoclonal gammopathy of
      undetermined significance patients result in an increased risk of venous and
      arterial thrombosis, infections, osteoporosis, and bone fractures. In addition,
      the small clone may occasionally be responsible for severe organ damage through
      the production of a monoclonal protein that has autoantibody activity or deposits
      in tissues. These disorders are rare and often require therapy directed at
      eradication of the underlying plasma cell or lymphoplasmacytic clone. In this
      review, we provide an overview of the clinical relevance of monoclonal gammopathy
      of undetermined significance. We also give general recommendations of how to
      diagnose and manage patients with monoclonal gammopathy of undetermined
      significance. 

PMID- 24658816
TI  - The erythroid function of transferrin receptor 2 revealed by Tmprss6 inactivation
      in different models of transferrin receptor 2 knockout mice.
AB  - Transferrin receptor 2 (TFR2) is a transmembrane glycoprotein expressed in the
      liver and in the erythroid compartment, mutated in a form of hereditary
      hemochromatosis. Hepatic TFR2, together with HFE, activates the transcription of
      the iron-regulator hepcidin, while erythroid TFR2 is a member of the
      erythropoietin receptor complex. The TMPRSS6 gene, encoding the liver-expressed
      serine protease matriptase-2, is the main inhibitor of hepcidin and inactivation
      of TMPRSS6 leads to iron deficiency with high hepcidin levels. Here we evaluate
      the phenotype resulting from the genetic loss of Tmprss6 in Tfr2 total (Tfr2(-/
      )) and liver-specific (Tfr2(LCKO)) knockout mice. Tmprss6(-/-)Tfr2(-/-) and
      Tmprss6(-/-)Tfr2(LCKO) mice have increased hepcidin levels and show iron
      deficiency anemia like Tmprss6(-/-)mice. However, while Tmprss6(-/-)Tfr2(LCKO)
      are phenotypically identical to Tmprss6(-/-) mice, Tmprss6(-/-)Tfr2(-/-) mice
      have increased red blood cell count and more severe microcytosis than Tmprss6(-/
      ) mice. In addition hepcidin expression in Tmprss6(-/-)Tfr2(-/-) mice is higher
      than in the wild-type animals, but lower than in Tmprss6(-/-) mice, suggesting
      partial inhibition of the hepcidin activating pathway. Our results prove that
      hepatic TFR2 acts upstream of TMPRSS6. In addition Tfr2 deletion causes a
      relative erythrocytosis in iron-deficient mice, which likely attenuates the
      effect of over-expression of hepcidin in Tmprss6(-/-) mice. Since liver-specific
      deletion of Tfr2 in Tmprss6(-/-) mice does not modify the erythrocyte count, we
      speculate that loss of Tfr2 in the erythroid compartment accounts for the
      hematologic phenotype of Tmprss6(-/-)Tfr2(-/-) mice. We propose that TFR2 is a
      limiting factor for erythropoiesis, particularly in conditions of iron
      restriction. 

PMID- 24658817
TI  - Markedly elevated serum total N-terminal propeptide of type I collagen is a novel
      marker for the diagnosis and follow up of patients with POEMS syndrome.

PMID- 24658818
TI  - The clinical significance of patients' sex in chronic lymphocytic leukemia.
AB  - We examined the prognostic influence of gender in chronic lymphocytic leukemia.
      Data from four randomized trials (involving 1821 patients) and three registration
      studies of stage-A disease (involving 1299 patients) were analyzed. Overall
      survival at 10 years was better for women than men in all trials (27% versus 15%;
      P=0.0001) and in the registration series (55% versus 43%; P<0.0001). More women
      than men in the trials were Binet stage A-progressive (26% versus 15%), but
      gender was an independent predictor of survival in multivariate analysis of
      clinical variables (P<0.0001). Women responded better to treatment (overall
      response 83%) than men (71%; P<0.0001), within each stage and age group, although
      fewer women than men received the full treatment dose (79% versus 85%; P=0.01).
      Women were more likely than men to experience toxicity (85% versus 78%, P=0.01),
      particularly gastro-intestinal toxicity (57% versus 42%, P<0.0001). Laboratory
      markers in the LRF CLL4 trial showed a significantly lower incidence in women
      than men of unmutated IGHV genes, raised beta-2 microglobulin, CD38 and Zap-70
      positivity and TP53 deletions/mutations and/or 11q deletions. We also highlight
      the higher male:female ratios in randomized trials versus studies of early
      chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Chronic
      lymphocytic leukemia in women runs a more benign clinical course than in men.
      Gender was also an independent predictor of response, suggesting that
      pharmacokinetic differences between the sexes and a possible effect of estrogens
      may contribute to the better outcome. Understanding the reasons for the different
      outcome by gender may improve patients' management. (LRF CLL4 controlled
      trials.com identifier: ISRCTN58585610). 

PMID- 24658819
TI  - Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase
      inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia.
AB  - Despite a well-recognized clinical benefit of the 2(nd)-generation tyrosine
      kinase inhibitor nilotinib in patients with imatinib-resistant/-intolerant or
      newly diagnosed chronic myeloid leukemia, recent evidence suggests that nilotinib
      has a propensity to increase the risk of occlusive arterial events, especially in
      patients with pre-existing cardiovascular risk factors. Given the key role of
      lipids in cardiovascular diseases, we studied the plasma lipid profile and global
      cardiovascular risk prior to and during nilotinib therapy in a series of 27
      patients in the setting of a prospective single center study. Data from a minimum
      1-year follow up showed that nilotinib significantly increased total, low- and
      high-density lipoprotein cholesterol within three months. Consequently, the
      proportion of patients with non-optimal low-density lipoprotein cholesterol
      increased from 48.1% to 88.9% by 12 months, leading to cholesterol-lowering drug
      intervention in 22.2% of patients. The proportion of patients with low levels of
      high-density lipoprotein cholesterol decreased from 40.7% to 7.4% by 12 months.
      In contrast, a significant decrease in triglycerides was observed. Global
      cardiovascular risk worsened in 11.1% of patients due to diabetes or occlusive
      arterial events. Whether hypercholesterolemia was the main driver of occlusive
      arterial events was uncertain: a longer follow up is necessary to ask whether
      nilotinib-induced hypercholesterolemia increases long-term risk of
      atherosclerotic diseases. Nevertheless, given key atherogenic properties of low
      density lipoprotein cholesterol, we conclude that when prescribing nilotinib,
      commitment to detect lipid disorders at baseline and during follow up is
      mandatory given their frequency, requirement for changes in lifestyle or drug
      intervention, and potential for long-term cardiovascular complications. 

PMID- 24658820
TI  - The predictive role of interim positron emission tomography for Hodgkin lymphoma
      treatment outcome is confirmed using the interpretation criteria of the Deauville
      five-point scale.
AB  - A retrospective, international, multicenter study was undertaken to assess: (i)
      the prognostic role of 'interim' positron emission tomography performed during
      treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients
      with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point
      scale for the interpretation of interim positron emission tomography scan. Two
      hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled.
      Fifty-three patients with early unfavorable and 207 with advanced-stage disease
      were treated with doxorubicin, bleomycin, vinblastine and dacarbazine +/-
      involved-field or consolidation radiotherapy. Positron emission tomography scan
      was performed at baseline and after two cycles of chemotherapy. Treatment was not
      changed according to the results of the interim scan. An international panel of
      six expert reviewers independently reported the scans using the Deauville five
      point scale, blinded to treatment outcome. Forty-five scans were scored as
      positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2
      110) months, 252 patients are alive and eight have died. The 3-year progression
      free survival rate was 83% for the whole study population, 28% for patients with
      interim positive scans and 95% for patients with interim negative scans
      (P<0.0001). The sensitivity, specificity, and negative and positive predictive
      values of interim positron emission tomography scans for predicting treatment
      outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst
      reviewers was good (Cohen's kappa 0.69-0.84). In conclusion, the prognostic role
      and validity of the Deauville five-point scale for interpretation of interim
      positron emission tomography scans have been confirmed by the present study. 

PMID- 24658821
TI  - A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple
      myeloma.

PMID- 24658824
TI  - Homologous region 1 of Plutella xylostella granulovirus functions as an enhancer
      for early gene expression.
AB  - Homologous regions (hrs) contained in genomes of baculoviruses have been shown to
      function as origins of viral DNA replication in alphabaculoviruses and
      betabaculoviruses, and as enhancers for early gene expression in
      alphabaculoviruses. The hr sequences of betabaculoviruses differ substantially
      from the ones of alphabaculoviruses. The enhancing property of betabaculovirus
      hrs has not been reported. In this study, transient assays were performed to
      investigate the effects of Plutella xylostella granulovirus (PlxyGV) hr1 on early
      gene expression of the virus. It was shown that hr1 stimulated reporter gene
      expression from the promoters of four early genes--ie1, dnapol, lef1, and lef9-
      independent of additional viral gene expression. The PlxyGV ie1 was shown to
      repress reporter gene expression from all four early gene promoters in a
      Trichoplusia ni cell line, both in the presence and absence of hr.

PMID- 24658822
TI  - Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural
      killer cells.
AB  - In this study, we aimed to investigate the pathways of recognition of acute
      lymphoblastic leukemia blasts by natural killer cells and to verify whether
      differences in natural killer cell activating receptor ligand expression among
      groups defined by age of patients, or presence of cytogenetic/molecular
      aberrations correlate with the susceptibility to recognition and killing. We
      analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and
      57 children. Pediatric blasts showed a significantly higher expression of Nec-2
      (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The
      differential expression of these ligands between adults and children was confined
      to B-lineage acute lymphoblastic leukemia with no known molecular alterations.
      Within molecularly defined subgroups of patients, a high surface expression of
      NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient
      age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible
      to natural killer-dependent lysis than B-lineage blasts without molecular
      aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing
      antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition
      in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological
      explanation of the different roles played by alloreactive natural killer cells in
      pediatric versus adult acute lymphoblastic leukemia and suggest that new natural
      killer-based strategies targeting specific subgroups of patients, particularly
      those BCR-ABL(+), are worth pursuing further. 

PMID- 24658825
TI  - The effect of parents' literacy skills and children's preliteracy skills on the
      risk of dyslexia.
AB  - The combination of investigating child and family characteristics sheds light on
      the constellation of risk factors that can ultimately lead to dyslexia. This
      family-risk study examines plausible preschool risk factors and their
      specificity. Participants (N = 196, 42 % girls) included familial risk (FR)
      children with and without dyslexia in Grade 3 and controls. First, we found
      impairments in phonological awareness, rapid naming, and letter knowledge in FR
      kindergartners with later dyslexia, and mild phonological-awareness deficits in
      FR kindergartners without subsequent dyslexia. These skills were better
      predictors of reading than arithmetic, except for rapid naming. Second, the
      literacy environment at home was comparable among groups. Third, having a
      dyslexic parent and literacy abilities of the non-dyslexic parent related to
      offspring risk of dyslexia. Parental literacy abilities might be viewed as
      indicators of offspring's liability for literacy difficulties, since parents
      provide offspring with genetic and environmental endowment. We propose an
      intergenerational multiple deficit model in which both parents confer cognitive
      risks. 

PMID- 24658826
TI  - Trauma, adversity, and parent-child relationships among young children
      experiencing homelessness.

PMID- 24658827
TI  - The influence of CYP3A, PPARA, and POR genetic variants on the pharmacokinetics
      of tacrolimus and cyclosporine in renal transplant recipients.
AB  - PURPOSE: Tacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4
      and CYP3A5. Several studies have demonstrated an association between the CYP3A5
      genotype and Tac dose requirements. Recently, CYP3A4, PPARA, and POR gene
      variants have been shown to influence CYP3A metabolism. The present study
      investigated potential associations between CYP3A5*3, CYP3A4*22, PPARA c.209-
      1003G>A and c.208+3819A>G, and POR*28 alleles and dose-adjusted concentrations
      (C/D) of Tac and CsA in 177 renal transplant patients early post-transplant.
      METHODS: All patients (n=177) were genotyped for CYP3A4*22, CYP3A5*3, POR*28,
      PPARA c.209-1003G>A, and PPARA c.208+3819A>G using real-time polymerase chain
      reaction (PCR) and melting curve analysis with allelespecific hybridization
      probes or PCR restriction fragment length polymorphisms (RFLP) methods. Drug
      concentrations and administered doses were retrospectively collected from patient
      charts at Oslo University Hospital, Rikshospitalet, Norway. One steady-state
      concentration was collected for each patient. RESULTS: We confirmed a significant
      impact of the CYP3A5*3 allele on Tac exposure. Patients with POR*28 and PPARA
      variant alleles demonstrated 15 % lower (P=0.04) and 19 % higher (P=0.01) Tac
      C0/D respectively. CsA C2/D was 53 % higher among CYP3A4*22 carriers (P=0.03).
      CONCLUSION: The results support the use of pre-transplant CYP3A5 genotyping to
      improve initial dosing of Tac, and suggest that Tac dosing may be further
      individualized by additional POR and PPARA genotyping. Furthermore, initial CsA
      dosing may be improved by pre-transplant CYP3A4*22 determination.

PMID- 24658828
TI  - Kidney stone risk following modern bariatric surgery.
AB  - Over the past 10 years, a variety of reports have linked bariatric surgery to
      metabolic changes that alter kidney stone risk. Most of these studies were
      retrospective, lacked appropriate controls, or involved bariatric patients with a
      variety of inclusion criteria. Despite these limitations, recent clinical and
      experimental research has contributed to our understanding of the pathophysiology
      of stone disease in this high-risk population. This review summarizes the urinary
      chemistry profiles that may be responsible for the increased kidney stone
      incidence seen in contemporary epidemiological bariatric studies, outlines the
      mechanisms of hyperoxaluria and potential therapies through a newly described
      experimental bariatric animal model, and provides a focused appraisal of
      recommendations for reducing stone risk in bariatric stone formers. 

PMID- 24658829
TI  - Robotic surgery in pediatric urology.
AB  - Minimally invasive laparoscopic procedures for urological diseases in children
      have proven to be safe and effective, with outcomes comparable to open
      procedures. Technical advances, including improved instruments and high
      definition cameras, have contributed to the expanded role of minimal invasive
      surgery (MIS) in children. The major drawback to laparoscopy has been the
      relatively steep learning curve due to the technical difficulties of suturing and
      the limitations of instrument dexterity and range of motion. Recently, robotic
      assisted laparoscopic surgery (RAS) has gained popularity in both adult and
      pediatric urology. RAS has several advantages over conventional laparoscopic
      surgery, particularly in the improved exposure via magnified 3-dimensional view
      and simplification of suturing with the increased degree of freedom and movement
      of the robotic arm. This review discusses the role of RAS in pediatric urology
      and provides technical aspects of RAS in specific urologic procedures as well. 

PMID- 24658831
TI  - Alternative sexualities: implications for the urologist.
AB  - Urologists routinely deal with sensitive issues of urinary function as well as
      sexuality in daily practice. Even experienced urologists may encounter patients
      who engage in sexual practices that are novel, unknown, or perhaps disturbing to
      the provider. This primer will serve as an introduction to sexual practices and
      lifestyle choices that may be foreign to many practicing urologists. It is by no
      means an exhaustive description of alternative sexualities, but will hopefully
      serve as a useful introduction to the topic and will enhance the ability of
      providers to care for, or appropriately refer, patients whose sexual practices
      and lifestyles may differ from their own. 

PMID- 24658830
TI  - Pelvic ultrasound evaluation for benign prostatic hyperplasia: prediction of
      obstruction.
AB  - Global improvements in water quality, management of infectious diseases, and
      other medical therapeutics have resulted in a growing population of healthy aging
      men. One obligate anatomic consequence of aging for these men is the development
      of benign prostatic hyperplasia (BPH) with secondary bladder outlet obstruction.
      Although the voiding symptoms associated with the change in bladder health over
      time predominantly impact the quality of a man's daily experience, there are also
      significant medical consequences of BPH that require intervention. It is a
      challenge to distinguish men who are at risk for these medical consequences from
      the much larger population of older men with voiding symptoms (lower urinary
      tract symptoms, LUTS). A variety of national guidelines have been developed to
      establish a diagnostic paradigm for meeting this challenge, but all suffer from
      inadequate sensitivity for the early identification of men at risk for permanent
      bladder injury. It is likely that the application of a thorough pelvic ultrasound
      designed to identify the pertinent anatomic aspects of both the bladder and
      prostate will improve the sensitivity of these diagnostic paradigms, with
      subsequent improvement in the outcomes for men with BPH/LUTS. 

PMID- 24658832
TI  - Emerging endoscopic imaging technologies for bladder cancer detection.
AB  - Modern urologic endoscopy is the result of continuous innovations since the early
      nineteenth century. White-light cystoscopy is the primary strategy for
      identification, resection, and local staging of bladder cancer. While highly
      effective, white light cystoscopy has several well-recognized shortcomings.
      Recent advances in optical imaging technologies and device miniaturization hold
      the potential to improve bladder cancer diagnosis and resection. Photodynamic
      diagnosis and narrow band imaging are the first to enter the clinical arena.
      Confocal laser endomicroscopy, optical coherence tomography, Raman spectroscopy,
      UV autofluorescence, and others have shown promising clinical and pre-clinical
      feasibility. We review their mechanisms of action, highlight their respective
      advantages, and propose future directions. 

PMID- 24658833
TI  - Ureteroscopy for treatment of upper urinary tract stones in children: technical
      considerations.
AB  - The incidence of pediatric urolithiasis is increasing. While many smaller stones
      may pass spontaneously, surgical therapy is sometimes warranted. Surgical options
      include shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, and
      open surgery. Ureteroscopy represents a minimally invasive approach, and it is
      increasingly being used to treat pediatric upper tract calculi. Ureteroscopy is
      performed under anesthesia and fluoroscopic guidance, with basket extraction or
      lithotripsy of the calculi. Technical considerations include active or passive
      ureteral dilatation, the use of ureteral access sheaths for larger stone burdens,
      and post-operative stent placement. The current pediatric literature suggests
      high success rates (equal to or surpassing shock wave lithotripsy) and low
      complication rates. However, concerns remain regarding feasibility in patients
      with variant anatomies and risk due to intra-operative radiation exposure. 

PMID- 24658834
TI  - The epidemiology of extra-articular manifestations in ankylosing spondylitis: a
      population-based matched cohort study.
AB  - OBJECTIVE: To assess the incidence and risks of common extra-articular
      manifestations (EAMs), that is, acute anterior uveitis (AAU), psoriasis and
      inflammatory bowel disease (IBD), in patients with ankylosing spondylitis (AS)
      compared with population-based controls. METHODS: All incident patients with AS
      (n=4101) from the UK Clinical Practice Research Datalink (1987-2012) were matched
      with up to seven control subjects without AS by year of birth, sex and practice
      (n=28,591). Incidence rates, cumulative incidence rates and adjusted (adj) HRs
      for the development of EAMs were calculated, with time-dependent adjustments for
      age, sex, comorbidity and medication use. RESULTS: At diagnosis of AS, the
      proportion of patients with an EAM was 11.4% for AAU, 4.4% for psoriasis and 3.7%
      for IBD. Incidence rates of EAMs were 8.9/1000 person-years for AAU, 3.4/1000
      person-years for psoriasis and 2.4 /1000 person-years for IBD in AS. The 20-year
      cumulative incidence was 24.5%, 10.1% and 7.5%, respectively. Risks of EAMs were
      1.5-fold to 16-fold increased versus controls, with an adj HR of 15.5 (95% CI
      11.6 to 20.7) for AAU, adj HR of 1.5 (95% CI 1.1 to 1.9) for psoriasis and adj HR
      of 3.3 (95% CI 2.3 to 4.8) for IBD. For psoriasis and IBD, the highest risks were
      found in the 1st years after diagnosis, while developing AAU continued to be
      increased also 10 years after diagnosis of AS. CONCLUSIONS: The risk of, in
      particular AAU, but also of psoriasis and IBD, is significantly increased in
      patients with AS compared with controls. Hazard patterns are different for each
      of the EAMs.

PMID- 24658835
TI  - Atherosclerosis and cardiovascular disease in systemic lupus erythematosus:
      effects of in vivo statin treatment.
AB  - OBJECTIVE: Statins may have beneficial vascular effects in systemic lupus
      erythematosus (SLE) beyond their cholesterol-lowering action, although the
      mechanisms involved are not completely understood. We investigated potential
      mechanisms involved in the efficacy of fluvastatin in preventing atherothrombosis
      in SLE. METHODS: Eighty-five patients with SLE and 62 healthy donors were
      included in the study. Selected patients (n=27) received 20 mg/day fluvastatin
      for 1 month. Blood samples were obtained before the start and at the end of
      treatment. Monocytes from five patients were treated in vitro with fluvastatin.
      RESULTS: Increased prothrombotic and inflammatory variables were found in
      patients with SLE. SLE monocytes displayed altered mitochondrial membrane
      potential and increased oxidative stress. Correlation and association analyses
      demonstrated a complex interplay among autoimmunity, oxidative stress,
      inflammation and increased risk of atherothrombosis in SLE. Fluvastatin treatment
      of patients for 1 month reduced the SLE Disease Activity Index and lipid levels,
      oxidative status and vascular inflammation. Array studies on monocytes
      demonstrated differential expression in 799 genes after fluvastatin treatment.
      Novel target genes and pathways modulated by fluvastatin were uncovered,
      including gene networks involved in cholesterol and lipid metabolism,
      inflammation, oxidative stress and mitochondrial activity. Electron microscopy
      analysis showed increased density volume of mitochondria in monocytes from
      fluvastatin-treated patients, who also displayed higher expression of genes
      involved in mitochondrial biogenesis. In vitro treatment of SLE monocytes
      confirmed the results obtained in the in vivo study. CONCLUSIONS: Our overall
      data suggest that fluvastatin improves the impairment of a redox-sensitive
      pathway involved in processes that collectively orchestrate the pathophysiology
      of atherothrombosis in SLE.

PMID- 24658836
TI  - A shorter telomere is the key factor in preventing cultured human  mesenchymal
      stem cells from senescence escape.
AB  - Mesenchymal stem cells (MSCs) from various animals undergo spontaneous
      transformation in vitro,establishing some malignant characteristics. However,this
      phenomenon seems seldom appearing in human (h)MSCs. To address the question
      whether the hMSCs really do not undergo the spontaneous transformation and
      why,the present study compared MSCs from two species under the same conditions,
      the commercialized primary hMSCs whose in vitro life span is very uniform, and
      the rat (r)MSCs whose spontaneous transformation in vitro is well defined.It was
      demonstrated that in rMSCs, there were small numbers of re-proliferating cells
      appearing after a substantial senescent period. These "senescence-escaped"rMSCs
      were highly proliferative and did not show any sign of growth arrest during the
      following subcultures upto observed passage 32. Whereas after entering
      senescence, hMSCs no longer re-proliferated and finally died from apoptosis.
      Compared with rMSCs, the hMSCs possessed a much shorter telomere, and lacked both
      telomerase reverse transcriptase expression and telomerase activity. When
      proliferating from pre-senescent to senescent stages,the hMSCs had a greater loss
      of relative telomere length(51 % in hMSC vs. 15 % in rMSC), but both cells
      displayed a similar average telomere shortening per population doubling (0.50 +/-
      0.06 kb in rMSC vs. 0.49 +/- 0.06 kbin hMSC; p > 0.05), indicating that the
      greater relative shortening of the hMSC telomeres was due to their original
      shorter length, rather than lack of telomere maintenance mechanisms. In
      conclusion, the hMSCs do not spontaneously initiate transformation, because they
      cannot escape senescence. This is particularly due to their much shorter
      telomere.

PMID- 24658837
TI  - Development of immunomonitoring of antibody-dependent cellular cytotoxicity
      against neuroblastoma cells using whole blood.
AB  - Neuroblastoma, a childhood tumour of neuroectodermal origin, accounts for 15 % of
      paediatric cancer deaths, which is often metastatic at diagnosis and despite
      aggressive therapies, it has poor long-term prognosis with high risk of
      recurrence. Monoclonal antibody (mAb) therapy targeting GD2, a disialoganglioside
      expressed on neuroblastoma, has shown promise in recent trials with natural
      killer cell (NK)-mediated antibody-dependent cellular cytotoxicity (ADCC) thought
      to be central to efficacy, although other immune effectors may be important. To
      further enhance therapy, immunomonitoring of patients is essential to elucidate
      the in vivo mechanisms of action and provides surrogate end points of efficacy
      for future clinical trials. Our aim was to establish a 'real-time' ex vivo
      wholeblood (WB) immunomonitoring strategy to perform within the logistical
      constraints such as limited sample volumes, anticoagulant effects, sample
      stability and shipping time. A fluorescent dye release assay measuring target
      cell lysis was coupled with flow cytometry to monitor specific effector response.
      Significant target cell lysis with anti-GD2 antibody (p < 0.05) was abrogated
      following NK depletion. NK up-regulation of CD107a and CD69 positively correlated
      with target cell lysis (r > 0.6). The ADCC activity of WB correlated with
      peripheral blood mononuclear cells (r > 0.95), although WB showed overall greater
      target cell lysis attributed to the combination of NK-mediated ADCC, CD16+
      granulocyte degranulation and complement- dependent cytotoxicity. Response was
      maintained in heparinised samples stored for 24 h at room temperature, but not 4 
      degrees C. Critically, the assay showed good reproducibility (mean % CV < 6.4)
      and was successfully applied to primary neuroblastoma samples. As such, WB
      provides a resourceful analysis of multiple mechanisms for efficient end point
      monitoring to correlate immune modulation with clinical outcome.

PMID- 24658838
TI  - Influence of natural killer cells and perforin-mediated cytolysis on the
      development of chemically induced lung cancer in A/J mice.
AB  - One alternative approach for the treatment of lung cancer might be the activation
      of the immune system using vaccination strategies. However, most of clinical
      vaccination trials for lung cancer did not reach their primary end points,
      suggesting that lung cancer is of low immunogenicity. To provide additional
      experimental information about this important issue, we investigated which type
      of immune cells contributes to the protection from lung cancer development.
      Therefore, A/J mice induced for lung adenomas/ adenocarcinomas by the tobacco
      specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were
      depleted of CD4+ or CD8+ T cells, CD11b+ macrophages, Gr-1+ neutrophils and
      asialo GM1+ natural killer (NK) cells. Subsequent analysis of tumour growth
      showed an increase in tumour number only in mice depleted of NK cells. Further
      asking by which mechanism NK cells suppressed tumour development, we neutralized
      several death ligands of the tumour necrosis factor (TNF) family known to be
      involved in NK cell-mediated cytotoxicity. However neither depletion of TNF
      alpha, TNF-related apoptosis-inducing ligand, TNF-like weak inducer of apoptosis
      or FasL alone nor in combination induced an augmentation of tumour burden. To
      show whether an alternative cell death pathway is involved, we next generated A/J
      mice deficient for perforin. After challenging with NNK, mice deficient for
      perforin showed an increase in tumour number and volume compared to wild-type A/J
      mice. In summary, our data suggest that NK cells and perforin-mediated cytolysis
      are critically involved in the protection from lung cancer giving promise for
      further immunotherapeutic strategies for this disease.

PMID- 24658840
TI  - Tunable multiferroic and bistable/complementary resistive switching properties of
      dilutely Li-doped BiFeO3 nanoparticles: an effect of aliovalent substitution.
AB  - We report a potential way to enhance and tune the multiferroic and resistive
      switching properties of BiFeO3 nanoparticles through dilute aliovalent Li(1+)
      doping (0.046 atomic percent) at the Fe(3+) sites of BiFeO3. The high purity of
      the samples and the extent of doping were confirmed by different physical
      characterizations. Enhanced multiferroic properties with a magnetic moment per Fe
      atom ~ 0.12 MUB and electric polarization ~ 49 MUC cm(-2) were observed in one of
      the Li(1+) doped samples. A phenomenological model has been proposed to support
      the observed magnetic behavior of the doped samples. From a potential application
      point of view, we further report on the doping concentration and polarization
      coercivity dependent highly stable resistive switching behavior (endurance cycles
      >10(3) and stability >10(6) s) of Li-doped BiFeO3 nanoparticles. The stable
      complementary resistive switching behavior (1 bit operation) for >50 cycles and
      under voltage pulse for 10(3) cycles in the doped BiFeO3 at a low operating bias
      is reported. Thus, dilute aliovalent Li(1+) doping enables tunability of the
      ferroic and resistive switching properties of BiFeO3and shows it to be a
      promising multiferroic material. 

PMID- 24658841
TI  - Differential expression of microRNAs in dormant bud of tea [Camellia sinensis
      (L.) O. Kuntze].
AB  - KEY MESSAGE: Expression analysis of miRNAs and understanding their target genes
      function in dormant tea bud might be used to identify molecular network panel and
      novel approaches for modulating dormancy in tea. Tea [Camellia sinensis (L) O.
      Kuntze, Theaceae] is an important commercial beverage crop manufactured from the
      apical bud and two leaves immediately below the bud. The yield and quality of tea
      depend on the vegetative growth of shoots and bud dormancy. The dormancy of bud
      is being regulated by many factors, such as mechanical, environmental and
      molecular mechanisms. MicroRNAs (miRNAs) are a newly identified class of small
      non-protein coding regulatory RNAs in both plants and animals which regulates
      gene expression at post-transcriptional level either by cleavage or translational
      inhibition of targeted mRNA transcripts. With these importances, the expression
      pattern of tea miRNAs was analyzed in active and dormant bud using stem-loop
      pulse RT-qPCR method. The results demonstrated the following expression pattern
      for highly up-regulated miRNAs, cs-miR 414[csmiR 408[cs-miR782[cs-miR169, and
      down-regulated miRNAs, cs-miR828[cs-miR1864[cs-miR852[csmiR1425 in dormant bud of
      tea. Furthermore, the role of target transcripts regulated by these miRNAs in
      relation to bud dormancy was discussed in detail. Therefore, the present study on
      the miRNA expression in tea will provide basis and considerably broaden the scope
      of understanding the function of miRNAs within the bud tissues and can serve as
      an initial point for RNA interference-based controlling strategies of bud
      dormancy in tea.

PMID- 24658839
TI  - Mapping the immunosuppressive environment in uterine tumors: implications for
      immunotherapy.
AB  - The major hurdle for cancer vaccines to be effective is posed by tumor immune
      evasion. Several common immune mechanisms and mediators are exploited by tumors
      to avoid immune destruction. In an attempt to shed more light on the
      immunosuppressive environment in uterine tumors, we analyzed the presence of PD
      L1, PDL2, B7-H4, indoleamine 2,3-dioxygenase (IDO), galectin- 1, galectin-3,
      arginase-1 activity and myeloid-derived suppressor cell (MDSC) infiltration. IDO,
      PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemistry. PDL2 was mostly
      expressed at low levels in these tumors. We found high IDO expression in 21 % of
      endometrial carcinoma samples and in 14 % of uterine sarcoma samples. For PD-L1
      and B7-H4, we found high expression in 92 and 90 % of endometrial cancers,
      respectively, and in 100 and 92 % of the sarcomas. Galectin-1 and 3 were analyzed
      in tissue lysates by ELISA, but we did not find an increase in both molecules in
      tumor lysates compared with benign tissues. We detected expression of galectin-3
      by fibroblasts, immune cells and tumor cells in single-cell tumor suspensions. In
      addition, we noted a highly significant increase in arginase-1 activity in
      endometrial carcinomas compared with normal endometria, which was not the case
      for uterine sarcomas. Finally, we could demonstrate MDSC infiltration in fresh
      tumor suspensions from uterine tumors. These results indicate that the PD-1/PD-L1
      interaction and B7-H4 could be possible targets for immune intervention in
      uterine cancer patients as well as mediation of MDSC function. These observations
      are another step toward the implementation of inhibitors of immunosuppression in
      the treatment of uterine cancer patients.

PMID- 24658842
TI  - A colorimetric organic chemo-sensor for Co2+ in a fully aqueous environment.
AB  - A new highly selective and sensitive colorimetric chemosensor 1 for Co(2+) was
      developed. The receptor 1 sensed Co(2+) by changing its color from yellow to
      orange in aqueous solution. Moreover, 1 could be used as a practical, visible
      colorimetric test kit for Co(2+).

PMID- 24658843
TI  - Altered pattern of the incretin effect as assessed by modelling  in individuals
      with glucose tolerance ranging from normal  to diabetic.
AB  - AIMS/HYPOTHESIS: Oral glucose elicits a higher insulin secretory response than
      intravenous glucose at matched glucose concentrations. This potentiation, known
      as the incretin effect, is typically expressed as the difference between the
      total insulin response to oral vs intravenous glucose. This approach does not
      describe the dynamics of insulin secretion potentiation. We developed a model for
      the simultaneous analysis of oral and isoglycaemic intravenous glucose responses
      to dissect the impact of hyperglycaemia and incretin effect on insulin secretion
      and beta cell function. METHODS: Fifty individuals (23 with normal glucose
      tolerance [NGT], 17 with impaired glucose tolerance [IGT] and ten with type 2
      diabetes) received an OGTT and an isoglycaemic test with measurement of plasma
      glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP). Our model featured an incretin
      potentiation factor (PINCR) for the dose-response function relating insulin
      secretion to glucose concentration, and an effect on early secretion (rate
      sensitivity). RESULTS: In NGT, PINCR rapidly increased and remained sustained
      during the whole OGTT (mean PINCR>1, p<0.009). The increase was transient in IGT
      and virtually absent in diabetes. Mean PINCR was significantly but loosely
      correlated with GLP-1 AUC (r=0.49, p<0.006), while the relationship was not
      significant for GIP. An incretin effect on rate sensitivity was present in all
      groups (p<0.002). CONCLUSIONS/INTERPRETATION: The onset of the incretin effect is
      rapid and sustained in NGT, transient in IGT and virtually absent in diabetes.
      The profiles of the incretin effect are poorly related to those of the incretin
      hormones.

PMID- 24658844
TI  - A brief overview of galactosemia newborn screening  in the United States.

PMID- 24658846
TI  - Implications of changing the amount of thickener in thickened infant formula for
      infants with dysphagia.
AB  - When a dysphagic infant is prescribed thickened infant formula (TIF) as a
      treatment method, some clinicians determine their own addition rates of thickener
      to meet the specific needs of the infant rather than relying on the directions on
      the tin. In this study the rheological behaviour of a TIF at different addition
      levels of thickener was measured to determine whether there was a difference in
      full rheological response and in viscosity. In addition, the time taken for the
      TIF to reach a near-stable viscosity was also measured. One hundred grams of
      Karicare(r) infant formula was made up according to the manufacturer's
      instructions and Karicare(r) feed thickener was added at levels of 2, 3, 4, 5,
      and 6 g, respectively. A strain-controlled rheometer (ARES) with Couette geometry
      was used to rheologically characterise the TIF at the different levels of
      thickener addition. There was a significant difference in viscosity between the
      low levels and the higher levels of addition thickener (p < 0.05). Also, the low
      levels of thickener addition showed Newtonian-like behaviour, whereas the higher
      levels of addition were shear-thinning. The time taken for the thickener to reach
      a near-stable viscosity was found to be 10 min. Guidelines for thickened infant
      formula need to take into account the different levels of thickener addition
      rates.

PMID- 24658845
TI  - Liver disease in infancy caused by oxysterol 7 alpha-hydroxylase deficiency:
      successful treatment with chenodeoxycholic acid.
AB  - A child of consanguineous parents of Pakistani origin developed jaundice at 5
      weeks and then, at 3 months, irritability, a prolonged prothrombin time, a low
      albumin, and episodes of hypoglycaemia. Investigation showed an elevated alanine
      aminotransferase with a normal gamma-glutamyl-transpeptidase. Analysis of urine
      by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) showed that the
      major peaks were m/z 480 (taurine-conjugated 3beta-hydroxy-5-cholenoic acid) and
      m/z 453 (sulphated 3beta-hydroxy-5-cholenoic acid). Analysis of plasma by gas
      chromatography-mass spectrometry (GC-MS) showed increased concentrations of 3beta
      hydroxy-5-cholenoic acid, 3beta-hydroxy-5-cholestenoic acid and 27
      hydroxycholesterol, indicating oxysterol 7 alpha-hydroxylase deficiency. The
      patient was homozygous for a mutation (c.1249C>T) in CYP7B1 that alters a highly
      conserved residue in oxysterol 7 alpha-hydroxylase (p.R417C) - previously
      reported in a family with hereditary spastic paraplegia type 5. On treatment with
      ursodeoxycholic acid (UDCA), his condition was worsening, but on chenodeoxycholic
      acid (CDCA), 15 mg/kg/d, he improved rapidly. A biopsy (after 2 weeks on CDCA),
      showed a giant cell hepatitis, an evolving micronodular cirrhosis, and steatosis.
      The improvement in liver function on CDCA was associated with a drop in the
      plasma concentrations and urinary excretions of the 3beta-hydroxy-Delta5 bile
      acids which are considered hepatotoxic. At age 5 years (on CDCA, 6 mg/kg/d), he
      was thriving with normal liver function. Neurological development was normal
      apart from a tendency to trip. Examination revealed pes cavus but no upper motor
      neuron signs. The findings in this case suggest that CDCA can reduce the activity
      of cholesterol 27-hydroxylase - the first step in the acidic pathway for bile
      acid synthesis.

PMID- 24658847
TI  - Validation of the videofluoroscopic dysphagia scale in various etiologies.
AB  - The videofluoroscopic dysphagia scale (VDS) was developed as an objective
      predictor of the prognosis of dysphagia after stroke. We evaluated the clinical
      validity of the VDS for various diseases. We reviewed the medical records of
      1,995 dysphagic patients (1,222 men and 773 women) who underwent
      videofluoroscopic studies in Seoul National University Hospital from April 2002
      through December 2009. Their American Speech-Language-Hearing Association's
      National Outcome Measurement System (ASHA NOMS) swallowing scale, clinical
      dysphagia scale (CDS), and VDS scores were evaluated on the basis of the clinical
      and/or videofluoroscopic findings by the consensus of two physiatrists. The
      correlations between the VDS and the other scales were calculated. The VDS
      displayed significant correlations with the ASHA NOMS swallowing scale and the
      CDS in every disease group (p < 0.001 in all groups, including central and
      peripheral nervous system disorders), and these correlations were more apparent
      for spinal cord injury, peripheral nerve system disorders, and neurodegenerative
      diseases (correlation coefficients between the VDS and the ASHA NOMS swallowing
      scale: -0.603, -0.602, and -0.567, respectively). This study demonstrated that
      the VDS is applicable to dysphagic patients with numerous etiologies that cause
      dysphagia

PMID- 24658848
TI  - Hand reanimation.
AB  - Brachial plexus disruption, major traumatic amputations, and Volkmann's
      contracture are all devastating injuries that present difficult reconstructive
      challenges. Advances in our understanding of nerve injury, regeneration, and
      refinement of microsurgical techniques have given rise to a number of therapeutic
      avenues over the last 4 decades. Hand reanimation aims to provide strength,
      stability, and mobility to a sensate hand. How this is achieved depends on a
      thorough understanding of the underlying pathophysiology, which in turn dictates
      what surgical modalities are suitable. Common to all reanimation procedures is
      the need to ensure full passive range of motion of the target joints prior to
      definitive surgery. Hand therapy is essential to prevent deleterious sequelae of
      injury, and to maximize rehabilitation following surgical reconstruction. Options
      for reanimation include nerve repair, nerve grafting, nerve transfer, tendon
      transfer, and free functioning muscle transfer. 

PMID- 24658849
TI  - The herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a
      neuroblastoma cells.
AB  - The herbal medicine Tong Luo Jiu Nao (TLJN) contains geniposide (GP) and
      ginsenoside Rg1 at a molar ratio of 10:1. Rg1 is the major component of another
      herbal medicine, panax notoginseng saponin (PNS). TLJN has been shown to
      strengthen brain function in humans, and in animals it improves learning and
      memory. We have previously shown that TLJN reduces amyloidogenic processing in
      Alzheimer's disease (AD) mouse models. Together this suggests TLJN may be a
      potential treatment for patients with dementia. Because chronic damage of the
      central nervous system by formaldehyde (FA) has been presented as a risk factor
      for age-associated cognitive dysfunction, in the present study we investigated
      the protective effect of both TLJN and GP in neuron-like cells exposed to FA. FA
      exposed murine N2a neuroblastoma cells were incubated with TLJN, its main
      ingredient GP, as well as PNS, to measure cell viability and morphology, the rate
      of apoptosis and expression of genes encoding Akt, FOXO3, Bcl2 and p53. The CCK-8
      assay, cytoskeletal staining and flow cytometry were used to test cell viability,
      morphology and apoptosis, respectively. Fluorescent quantitative real-time PCR
      (qRT-PCR) was used to monitor changes in gene expression, and HPLC to determine
      the rate of FA clearance. Treatment of N2a cells with 0.09 mmol L(-1) FA for 24 h
      significantly reduced cell viability, changed cell morphology and promoted
      apoptosis. Both TLJN and GP conferred neuroprotection to FA-treated N2a cells,
      whereas PNS, which had to be used at lower concentrations because of its
      toxicity, did not. Our data demonstrate that TLJN can rescue neuronal damage
      caused by FA and that its main ingredient, GP, has a major role in this efficacy.
      This presents purified GP as a drug or lead compound for the treatment of AD.

PMID- 24658850
TI  - RNA-binding proteins in neurological diseases.
AB  - Emerging studies support that RNA-binding proteins (RBPs) play critical roles in
      human biology and pathogenesis. RBPs are essential players in RNA processing and
      metabolism, including pre-mRNA splicing, polyadenylation, transport,
      surveillance, mRNA localization, mRNA stability control, translational control
      and editing of various types of RNAs. Aberrant expression of and mutations in RBP
      genes affect various steps of RNA processing, altering target gene function. RBPs
      have been associated with various diseases, including neurological diseases.
      Here, we mainly focus on selected RNA-binding proteins including Nova-1/Nova-2,
      HuR/HuB/HuC/HuD, TDP-43, Fus, Rbfox1/Rbfox2, QKI and FMRP, discussing their
      function and roles in human diseases.

PMID- 24658851
TI  - Crystal-phase control of molybdenum carbide nanobelts for dehydrogenation of
      benzyl alcohol.
AB  - Belt-shaped molybdenum carbides in alpha- and beta-phases were synthesized by
      reducing and carburizing a nano-sized alpha-MoO3 precursor with hydrocarbon
      hydrogen mixtures at appropriate temperatures; the beta-Mo2C nanobelts with a
      higher fraction of coordinatively unsaturated Mo sites were more active than the
      alpha-MoC1-x nanobelts in dehydrogenation of benzyl alcohol to benzaldehyde. 

PMID- 24658852
TI  - Burnout among physiotherapists and length of service.
AB  - OBJECTIVES: The aim of this study was to identify factors that contribute to the
      development of burnout among physiotherapists with different length of service in
      physiotherapy. MATERIAL AND METHODS: The following research tools were used to
      study burnout: the Life Satisfaction Questionnaire (LSQ), based on FLZ
      (Fragebogen zur Lebenszufriedenheit) by Frahrenberg, Myrtek, Schumacher, and
      Brahler; the Burnout Scale Inventory (BSI) by Steuden and Okla; and an ad hoc
      questionnaire to collect socio-demographic data. The survey was anonymous and
      voluntary and involved a group of 200 active physiotherapists working in Poland.
      RESULTS: A statistical analysis revealed significant differences in overall life
      satisfaction between length-of-service groups (p = 0.03). Physiotherapists with
      more than 15 years of service reported greater satisfaction than those with less
      than 5 years and between 5 and 15 years of service. The results suggest that
      burnout in those with 5-15 years of service is higher in physiotherapists working
      in health care centers and increases with age and greater financial satisfaction,
      while it decreases with greater satisfaction with friend and family relations and
      greater satisfaction with one's work and profession. In those with more than 15
      years of service, burnout increases in the case of working in a setting other
      than a health care or educational center and decreases with greater satisfaction
      with one's work and profession. CONCLUSIONS: Job satisfaction and a satisfying
      family life prevent burnout among physiotherapists with 5-15 years of service in
      the profession. Financial satisfaction, age and being employed in health care may
      cause burnout among physiotherapists with 5-15 years of service. Physiotherapists
      with more than 15 years of service experience more burnout if they work in a
      setting other than a health care or educational center and less burnout if they
      are satisfied with their profession.

PMID- 24658853
TI  - The SDF-1/CXCR4 axis induces epithelial-mesenchymal transition in hepatocellular
      carcinoma.
AB  - Hepatic stellate cells play a role in the migration process of hepatocellular
      carcinoma cells. Here, we address the role of the stromal-derived factor-1/CXC
      chemokine receptor 4 (SDF-1/CXCR4) axis on hepatocellular carcinoma progression.
      The expression of the SDF-1 and the CXCR4 was determined through western blotting
      and real-time PCR analysis using hepatic stellate (LX02) and hepatocellular
      carcinoma (MHCC97, SMMC7721, Hep3B, and HepG2) cell lines depleted of CXCR4 using
      shRNA. The migration of hepatocellular carcinoma cells following exogenous
      treatment with SDF-1 or in co-culture cell systems was measured using the
      Transwell assay. In parallel, the expression of epithelial-mesenchymal transition
      (EMT) markers was also determined. We found that SDF-1 is highly expressed in the
      hepatic stellate cell line LX02 and that the hepatocellular carcinoma cells
      express high levels of CXCR4. Co-culturing hepatocellular carcinoma cells with
      LX02 or exogenous treatment with SDF-1 induced an EMT as shown by increased
      migration. In contrast, ablation of CXCR4 expression in HepG2 cells attenuated
      the migration of HepG2 cells and suppressed the EMT. Thus, hepatic stellate cells
      can promote hepatocellular carcinoma cell invasion through the SDF-1/CXCR4 axis.

PMID- 24658854
TI  - MicroRNA-124 inhibits proliferation and induces apoptosis by directly repressing
      EZH2 in gastric cancer.
AB  - MicroRNA-124 (miR-124), a pivotal member of the p53 network, was found to be down
      regulated in multiple types of tumors and further reported as tumor suppressor
      microRNA. In this study, we found that miR-124 was down-regulated in gastric
      cancer cell lines and specimens. Restoration of miR-124 expression inhibited the
      proliferation and colony formation of gastric cancer cells. EZH2 (enhancer of
      zeste homolog 2), which has been shown to be an important transcription factor
      involved in the proliferation and metastasis of tumor cells, was here confirmed
      to be a direct target gene of miR-124. On the other hand, silencing EZH2 also
      inhibits cell proliferation of gastric cancer cells. Furthermore, the treatment
      combining miR-124 with 5-fluorouracil (5-FU) significantly showed more efficient
      anti-tumor effects than single treatment of miR-124 or 5-FU, and over-expression
      of miR-124 suppresses the tumor growth in vivo. Our study indicate that miR-124
      can suppress gastric cancer cell growth by directly targeting the EZH2 gene and
      sensitize the treatment effect of 5-FU. Therefore, miR-124 shows tumor
      suppressive activity and may be a new and useful approach of gastric cancer
      therapy.

PMID- 24658856
TI  - Implications of within-fiber temporal coding for perceptual studies of F0
      discrimination and discrimination of harmonic and inharmonic tone complexes.
AB  - Recent psychophysical studies suggest that normal-hearing (NH) listeners can use
      acoustic temporal-fine-structure (TFS) cues for accurately discriminating shifts
      in the fundamental frequency (F0) of complex tones, or equal shifts in all
      component frequencies, even when the components are peripherally unresolved. The
      present study quantified both envelope (ENV) and TFS cues in single auditory
      nerve (AN) fiber responses (henceforth referred to as neural ENV and TFS cues)
      from NH chinchillas in response to harmonic and inharmonic complex tones similar
      to those used in recent psychophysical studies. The lowest component in the tone
      complex (i.e., harmonic rank N) was systematically varied from 2 to 20 to produce
      various resolvability conditions in chinchillas (partially resolved to completely
      unresolved). Neural responses to different pairs of TEST (F0 or frequency
      shifted) and standard or reference (REF) stimuli were used to compute shuffled
      cross-correlograms, from which cross-correlation coefficients representing the
      degree of similarity between responses were derived separately for TFS and ENV.
      For a given F0 shift, the dissimilarity (TEST vs. REF) was greater for neural TFS
      than ENV. However, this difference was stimulus-based; the sensitivities of the
      neural TFS and ENV metrics were equivalent for equal absolute shifts of their
      relevant frequencies (center component and F0, respectively). For the F0
      discrimination task, both ENV and TFS cues were available and could in principle
      be used for task performance. However, in contrast to human performance, neural
      TFS cues quantified with our cross-correlation coefficients were unaffected by
      phase randomization, suggesting that F0 discrimination for unresolved harmonics
      does not depend solely on TFS cues. For the frequency-shift (harmonic-versus
      inharmonic) discrimination task, neural ENV cues were not available. Neural TFS
      cues were available and could in principle support performance in this task;
      however, in contrast to human-listeners' performance, these TFS cues showed no
      dependence on N. We conclude that while AN-fiber responses contain TFS-related
      cues, which can in principle be used to discriminate changes in F0 or equal
      shifts in component frequencies of peripherally unresolved harmonics, performance
      in these two psychophysical tasks appears to be limited by other factors (e.g.,
      central processing noise).

PMID- 24658855
TI  - Auditory processing disorders with and without central auditory discrimination
      deficits.
AB  - Auditory processing disorder (APD) is defined as a processing deficit in the
      auditory modality and spans multiple processes. To date, APD diagnosis is mostly
      based on the utilization of speech material. Adequate nonspeech tests that allow
      differentiation between an actual central hearing disorder and related disorders
      such as specific language impairments are still not adequately available. In the
      present study, 84 children between 6 and 17 years of age (clinical group),
      referred to three audiological centers for APD diagnosis, were evaluated with
      standard audiological tests and additional auditory discrimination tests. Latter
      tests assessed the processing of basic acoustic features at two different stages
      of the ascending central auditory system: (1) auditory brainstem processing was
      evaluated by quantifying interaural frequency, level, and signal duration
      discrimination (interaural tests). (2) Diencephalic/telencephalic processing was
      assessed by varying the same acoustic parameters (plus signals with sinusoidal
      amplitude modulation), but presenting the test signals in conjunction with noise
      pulses to the contralateral ear (dichotic(signal/noise) tests). Data of children
      in the clinical group were referenced to normative data obtained from more than
      300 normally developing healthy school children. The results in the audiological
      and the discrimination tests diverged widely. Of the 39 children that were
      diagnosed with APD in the audiological clinic, 30 had deficits in auditory
      performance. Even more alarming was the fact that of the 45 children with a
      negative APD diagnosis, 32 showed clear signs of a central hearing deficit. Based
      on these results, we suggest revising current diagnostic procedure to evaluate
      APD in order to more clearly differentiate between central auditory processing
      deficits and higher-order (cognitive and/or language) processing deficits.

PMID- 24658857
TI  - [Molecular genetics: significance in hereditary eye diseases].

PMID- 24658858
TI  - [Leber's hereditary optic neuropathy - phenotype, genetics, therapeutic options].
AB  - Leber's hereditary optic neuropathy is a rare genetic disorder affecting the
      retinal ganglion cells leading to a persistent severe bilateral loss of visual
      acuity within weeks or months. Males are much more likely to be affected than
      females, disease onset in most cases takes place between age 15 and 35 years. The
      disease is caused by point mutations in the mitochondrial DNA. The penetrance of
      the disease is incomplete, i.e., not all mutation carriers develop clinical
      symptoms. The phenotype is relatively uniform, but age at onset, severity and
      prognosis may vary even within the same family. Environmental and endocrine
      factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors
      are discussed to influence penetrance as well as interindividual and
      intrafamilial variability. However, only cigarette smoking and excessive alcohol
      consumption have been shown to trigger disease onset. The disease is
      characterised by a central visual field defect, impaired colour vision and
      fundoscopically a peripapillary microangiopathy in the acute phase. Most patients
      end up after some months with a severe visual loss below 0.1 and in most cases
      there is no significant improvement of visual acuity in the course. In rare cases
      patients experience a mostly partial visual recovery which depends on the type of
      mutation. For confirmation of the diagnosis a detailed ophthalmological
      examination with fundoscopy, family history and genetic analysis of the
      mitochondrial DNA is needed. To date, there is no proven causal therapy, but at
      early disease stages treatment with idebenone can be tried. 

PMID- 24658859
TI  - [Current therapeutic approaches in inherited retinal degeneration: from genes to
      chip].
AB  - Different strategies for the treatment of inherited photoreceptor degeneration
      are currently being investigated, with each of these approaches facing specific
      challenges. Gene therapy, for instance, may be feasible only for genetically well
      defined pathologies. However, inherited retinal disorders are genetically highly
      heterogeneous and early onset disorders may restrict the therapeutic window. The
      majority of currently developed molecular approaches aim at the reconstitution of
      physiologically important functions in RPE and photoreceptor. Neuroprotection
      attempts to prolong cell survival and proper function via sustained delivery
      systems that fulfil a long-term dynamic reservoir function for therapeutic
      neuroprotective compounds. Cell-based approaches include replacement strategies
      such as cell transplantation, the implantation of prosthetic devices or
      optogenetics. They aim at replacing lost neurosensory functions of the retina.
      This short review aims at providing an insight into current therapeutic
      strategies and future treatment options for retinal disorders. Pharmacological
      and nutritional support strategies are only briefly discussed as we focus here on
      molecular and prosthetic therapeutic approaches. 

PMID- 24658860
TI  - [Gene replacement therapy in achromatopsia type 2].
AB  - Achromatopsia is an autosomal recessive inherited retinal disease caused by a
      complete loss of cone photoreceptor function. About 80 % of achromatopsia
      patients show mutations in the alpha or beta subunit (A3 and B3) of the cGMP
      controlled cation channel CNG (cyclic nucleotide-gated channel) of cone
      photoreceptors. Homologous to the human disease, CNGA3 deficient mice reveal a
      loss of cone specific functionality leading to degeneration of affected cone
      photoreceptors. The Institute for Ophthalmic Research in Tubingen has now
      succeeded in curing achromatopsia ACHM2 in an animal model. In this article, we
      explain the recombinant adeno-associated virus-based approach in detail.
      Furthermore, applied non-invasive diagnostic techniques for quality and success
      control, ERG, SLO and OCT, are described. The success of the therapy is indicated
      by a restored cone photoreceptor function as well as the neuronal processing of
      retinal signals resulting in a specific, cone-mediated behaviour. The outstanding
      results derived from the animal model are the starting point for the first human
      translation of a gene therapy for achromatopsia in Germany. 

PMID- 24658861
TI  - [Demodex folliculorum: diagnosis and therapy today].
AB  - Demodex folliculorum is an ectoparasite found in eye lashes. A Demodex-associated
      blepharoconjunctivitis is common. Demodex are diagnosed via microscopy in a drop
      of oil after epilation of a few eye lashes. You can often watch the mites in
      movement under the microscope. Treatment includes lid hygiene and metronidazole
      gel 1-2 %. The treatment often improves the symptoms of the patient. Demodex
      folliculorum is often found in patients with persistent blepharoconjunctivitis.
      Every ophthalmologist should have a microscope to find the mites. Then you will
      be able to treat the patients in an early stage. 

PMID- 24658862
TI  - [Reconstruction of isolated orbital floor fractures with a prefabricated titanium
      mesh].
AB  - PURPOSE: Concerning safety and efficiency in surgery of isolated orbital floor
      fractures, several treatment modalities are being discussed. It is a matter of
      recent interest that prefabricated titanium meshes provide significant
      advantages. The purpose of this study was to review the usability of the
      MatrixORBITAL(r) plate. MATERIAL AND METHODS: In a prospective study we evaluated
      10 patients (June 2011 to November 2013) with an isolated orbital floor fracture.
      All patients in the study group had undergone reconstruction with the
      MatrixORBITAL(r) plate. For purposes of analysis were recorded: age, gender,
      fracture category according to Jaquiery et al. (2007), duration of surgery,
      complications, globe motility (Harms wall), exophthalmometry, function of the
      infraorbital nerve, evaluation of facial symmetry and aesthetic as well as
      personal contentment of the patient. A reference group received a PDS(r) sheet,
      an antral balloon or other materials. RESULTS: In the study group (2 women and 8
      men aged between 26 and 83 years) all cases presented a large disruption of the
      orbital floor (> 2 cm2 bony defect; category II-III). Volume changes were
      universally associated with diplopia, but only in two cases with an entrapment of
      the inferior rectus muscle. The mean duration of the operation was 110 minutes
      (minimum 50, maximum 135 minutes). Postoperatively diplopia was decreasing in all
      cases. None of the patients had a significant impairment of visus and no
      reoperation was necessary. The analysis of functional outcomes between the groups
      mesh, PDS sheet and antral balloon revealed no significant differences.
      CONCLUSIONS: Based on this experience and due to good intraoperative handling,
      the authors recommend the prefabricated titanium plate in the treatment of
      isolated orbital wall fractures or in combination with the medial wall despite
      the material costs.

PMID- 24658864
TI  - [Activities of the tissue transplantation and biotechnology section of the German
      Ophthalmological Society: report 2011 and 2012].

PMID- 24658863
TI  - [Comparison of canaloplasty with trabeculectomy].
AB  - BACKGROUND: Trabeculectomy (TET) is still the gold standard in incisional
      glaucoma surgery. It achieves an efficient intraocular pressure (IOP) reduction.
      Unfortunately postsurgical complications of the procedure are frequent.
      Canaloplasty is a non-penetrating procedure, which aims at restoration of the
      natural aqueous outflow pathways, without subconjunctival drainage. AIM: This
      study has compared both surgical procedures concerning IOP, defined success
      criteria, postoperative medication, visual acuity and postoperative
      complications/interventions. PATIENTS AND METHODS: In a retrospective study 22
      eyes after trabeculectomy and 22 eyes after canaloplasty were included. IOP,
      complete and qualified success, postoperative medication, visual acuity and
      complications/interventions were recorded at 6 month, 12 month and at last follow
      up postoperatively. RESULTS: The mean IOP in the trabeculectomy and canaloplasty
      groups decreased from 23.91 +/- 10.68 mmHg to 10.82 +/- 3.67 mmHg and from 23.68
      +/- 7.57 mmHg to 14.50 +/- 3.80 mmHg, respectively. The postoperative
      complications and interventions between the two groups did not reveal a
      statistically significant difference. Complete success (IOP < 21 mmHg and 20 %
      IOP reduction from baseline without medication) was achieved in 18 eyes (81.8 %)
      after trabeculectomy and in 11 eyes (50.0 %) after canaloplasty (p = 0.026).
      CONCLUSION: Canaloplasty and trabeculectomy are safe and effective procedures in
      the treatment of open-angle glaucoma. Both surgical methods reduce the IOP and
      the postoperative medication to a statistically significant extent.
      Trabeculectomy attains higher long-term complete success rates accompanied by
      slightly increased early postoperative complication rates (n. s.), compared to
      canaloplasty.

PMID- 24658865
TI  - [Meeting report -- retinal research 2013 in Germany].

PMID- 24658866
TI  - Stage at breast cancer diagnosis and distance from diagnostic hospital in a
      periurban setting: a South African public hospital case series of over 1,000
      women.
AB  - Advanced stage at diagnosis contributes to low breast cancer survival rates in
      sub-Saharan Africa. Living far from health services is known to delay
      presentation, but the effect of residential distance to hospital, the radius at
      which this effect sets in and the women most affected have not been quantified.
      In a periurban South African setting, we examined the effect of a geographic
      information system (GIS)-measured straight-line distance, from a patient's
      residence to diagnostic hospital, on stage at diagnosis in 1,071 public-sector
      breast cancer patients diagnosed during 2006-2012. Generalized linear models were
      used to estimate risk ratios for late stage (stage III/IV vs. stage I/II)
      associated with distance, adjusting for year of diagnosis, age, race and
      socioeconomic indicators. Mean age of patients was 55 years, 90% were black
      African and diagnoses were at stages I (5%), II (41%), III (46%) and IV (8%).
      Sixty-two percent of patients with distances >20 km (n = 338) had a late stage at
      diagnosis compared to 50% with distances <20 km (n = 713, p = 0.02). Risk of late
      stage at diagnosis was 1.25-fold higher (95% CI: 1.09, 1.42) per 30 km. Effects
      were pronounced in an underrepresented group of patients over age 70. This
      positive stage-distance association held to 40 km, and plateaued or slightly
      reversed in patients (9%) living beyond this distance. Studies of woman and the
      societal and healthcare-level influences on these delays and on the late stage at
      diagnosis distribution are needed to inform interventions to improve diagnostic
      stage and breast cancer survival in this and similar settings. 

PMID- 24658867
TI  - The role of supported joint engagement and parent utterances in language and
      social communication development in children with autism spectrum disorder.
AB  - This study examined associations between three parent-child engagement states and
      social communication, expressive language, and receptive language at 8 month
      follow-up, in 63 preschool-age children with autism spectrum disorder. We extend
      the literature on supported joint engagement by dividing this state into higher
      order (HSJE) and lower order types, with HSJE involving greater reciprocity in
      toy play. We also examined parents' follow-in utterances that co-occurred with
      each state. We found that only HSJE predicts later social communication and
      expressive language, while object engagement predicts receptive language. HSJE
      combined with follow-in utterances (HSJE+FI) predicts all three outcomes when
      controlling for HSJE+FI in other engagement states. When controlling for total
      HSJE, HSJE+FI is predictive of receptive language.

PMID- 24658868
TI  - Spatial transformations of bodies and objects in adults with autism spectrum
      disorder.
AB  - Previous research into autism spectrum disorder (ASD) has shown people with
      autism to be impaired at visual perspective taking. However it is still unclear
      to what extent the spatial mechanisms underlying this ability contribute to these
      difficulties. In the current experiment we examine spatial transformations in
      adults with ASD and typical adults. Participants performed egocentric
      transformations and mental rotation of bodies and cars. Results indicated that
      participants with ASD had general perceptual differences impacting on response
      times across tasks. However, they also showed more specific differences in the
      egocentric task suggesting particular difficulty with using the self as a
      reference frame. These findings suggest that impaired perspective taking could be
      grounded in difficulty with the spatial transformation used to imagine the self
      in someone else's place.

PMID- 24658869
TI  - Optimal image reconstruction for detection and characterization of small
      pulmonary nodules during low-dose CT.
AB  - OBJECTIVES: To optimize the slice thickness/overlap parameters for image
      reconstruction and to study the effect of iterative reconstruction (IR) on
      detectability and characterization of small non-calcified pulmonary nodules
      during low-dose thoracic CT. MATERIALS AND METHODS: Data was obtained from
      computer simulations, phantom, and patient CTs. Simulations and phantom CTs were
      performed with 9 nodules (5, 8, and 10 mm with 100, -630, and -800 HU). Patient
      data were based on 11 ground glass opacities (GGO) and 9 solid nodules. For each
      analysis the nodules were reconstructed with filtered back projection and IR
      algorithms using 10 different combinations of slice thickness/overlap (0.5-5 mm).
      The attenuation (CT#) and the contrast to noise ratio (CNR) were measured.
      Spearman's coefficient was used to correlate the error in CT# measurements and
      slice thickness. Paired Student's t test was used to measure the significance of
      the errors. RESULTS: CNR measurements: CNR increases with increasing slice
      thickness/overlap for large nodules and peaks at 4.0/2.0 mm for smaller ones. Use
      of IR increases the CNR of GGOs by 60 %. CT# measurements: Increasing slice
      thickness/overlap above 3.0/1.5 mm results in decreased CT# measurement accuracy.
      CONCLUSION: Optimal detection of small pulmonary nodules requires slice
      thickness/overlap of 4.0/2.0 mm. Slice thickness/overlap of 2.0/2.0 mm is
      required for optimal nodule characterization. IR improves conspicuity of small
      ground glass nodules through a significant increase in nodule CNR. KEY POINTS: *
      Slice thickness/overlap affects the accuracy of pulmonary nodule detection and
      characterization. * Slice thickness >=3 mm increases the risk of misclassifying
      small nodules. * Optimal nodule detection during low-dose CT requires 4.0/2.0-mm
      reconstructions. * Optimal nodule characterization during low-dose CT requires
      2.0/2.0-mm reconstructions. * Iterative reconstruction improves the CNR of ground
      glass nodules by 60 %.

PMID- 24658870
TI  - Gadoxetic acid enhanced MRI for differentiation of FNH  and HCA: a single centre
      experience.
AB  - OBJECTIVES: Evaluation of enhancement characteristics of histopathologically
      confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs)
      with gadoxetic acid-enhanced MRI. METHODS: Sixty-eight patients with 115
      histopathologically proven lesions (FNHs, n=44; HCAs, n=71) examined with
      gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference:
      surgical resection, n=53 patients (lesions: FNHs, n=37; HCAs, n=53); biopsy, n=15
      (lesions: FNHs, n=7; HCAs, n=18)). Two radiologists evaluated all MR images
      regarding morphological features as well as the vascular and hepatocyte-specific
      enhancement in consensus. RESULTS: For the hepatobiliary phase, relative
      enhancement of the lesions and lesion to liver enhancement were significantly
      lower for HCAs (mean, 48.7 (+/-48.4)%and 49.4 (+/-33.9) %) compared to FNHs
      (159.3 (+/-92.5) %; and 151.7 (+/-79) %; accuracy of 89%and 90 %, respectively;
      P<0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the
      hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior
      to all other morphological and dynamic vascular criteria alone and in combination
      (accuracy, 54-85 %). CONCLUSIONS: For differentiation of FNHs and HCAs by means
      of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior
      to all other criteria alone and in combination. KEY POINTS: EOB-MRI is well
      suited to differentiate FNHs and hepatocellular adenomas. For this purpose
      hepatobiliary phase is superior to unenhanced and dynamic imaging. Hepatobiliary
      phase (peripheral) hyper- or isointensity is typical for FNH. Hepatobiliary phase
      hypointensity is typical for hepatocellular adenomas. EOB-MRI helps to avoid
      misinterpretations of benign hepatocellular lesions.

PMID- 24658871
TI  - Application of the diffusion kurtosis model for the study of breast lesions.
AB  - OBJECTIVES: To evaluate diffusion-weighted imaging (DWI) and diffusion kurtosis
      imaging (DKI) in the differentiation and characterisation of breast lesions.
      METHODS: Thirty-six women underwent breast magnetic resonance imaging (MRI)
      including a DWI sequence with multiple b-values (50-3,000 s/mm(2)). Mean values
      for apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis
      (MK) were calculated by lesion type and histological subtype. Differences and
      correlation between parameters were determined. RESULTS: Forty-four lesions were
      found. There were significant differences between benign and malignant lesions
      for all parameters (ADC, p = 0.017; MD, p = 0.028; MK, p = 0.017). ADC and MD
      were higher for benign (1.96 +/- 0.41 * 10(-3) and 2.17 +/- 0.42 * 10(-3)
      mm(2)/s, respectively) than for malignant lesions (1.33 +/- 0.18 * 10(-3) and
      1.52 +/- 0.50 * 10(-3) mm(2)/s). MK was higher for malignant (0.61 +/- 0.27) than
      benign lesions (0.37 +/- 0.18). We found differences between invasive ductal
      carcinoma (IDC) and fibroadenoma (FA) for all parameters (ADC, MD and MK): p =
      0.016, 0.022 and 0.016, respectively. FA and fibrocystic change (FC) showed
      differences only in MK (p = 0.016). CONCLUSIONS: Diffusion in breast lesions
      follows a non-Gaussian distribution. MK enables differentiation and
      characterisation of breast lesions, providing new insights into microstructural
      complexity. To confirm these results, further investigation in a broader sample
      should be performed.

PMID- 24658872
TI  - Sniff and run-the chemistry of attraction.

PMID- 24658873
TI  - Customised osteotomy guides and endoprosthetic reconstruction for periacetabular
      tumours.
AB  - PURPOSE: We sought to analyse clinical and oncological outcomes of patients after
      guided resection of periacetabular tumours and endoprosthetic reconstruction of
      the remaining defect. METHODS: From 1988 to 2008, we treated 56 consecutive
      patients (mean age 52.5 years, 41.1 % women). Patients were followed up either
      until death or February 2011 (mean follow up 5.5 years, range 0.1-22.5, standard
      deviation +/- 5.3). Kaplan-Meier analysis was used to estimate survival rates.
      RESULTS: Disease-specific survival was 59.9 % at five years and 49.7 % at ten and
      20 years, respectively. Wide resection margins were achieved in 38 patients,
      whereas 11 patients underwent marginal and seven intralesional resection.
      Survival was significantly better in patients with wide or marginal resection
      than in patients with intralesional resection (p = 0.022). Survival for patients
      with secondary tumours was significantly worse than for patients with primary
      tumours (p = 0.003). In 29 patients (51.8 %), at least one reoperation was
      necessary, resulting in a revision-free survival of 50.5 % at five years, 41.1 %
      at ten years and 30.6 % at 20 years. Implant survival was 77.0 % at five years,
      68.6 % at ten years and 51.8 % at 20 years. A total of 35 patients (62.5 %)
      experienced one or more complications after surgery. Ten of 56 patients (17.9 %)
      experienced local recurrence after a mean of 8.9 months. The mean postoperative
      Musculoskeletal Tumor Society (MSTS) score was 18.1 (60.1 %). CONCLUSION: The
      surgical approach assessed in this study simplifies the process of tumour
      resection and prosthesis implantation and leads to acceptable clinical and
      oncological outcomes.

PMID- 24658874
TI  - Morbidity of graft harvesting versus bone marrow aspiration in cell regenerative
      therapy.
AB  - PURPOSE: Using bone marrow mesenchymal stem cells (MSCs) with aspiration from the
      iliac crest is commonly used in reconstructive orthopaedic surgery. Because bone
      marrow aspiration is a percutaneous technique, the morbidity as compared with the
      classical bone graft should be decreased. METHOD: Therefore in a retrospective
      review of 523 consecutive cases of bone marrow aspiration performed at the Henri
      Mondor Hospital from 1990 to 2006 for the treatment of fractures, minor and major
      complications were identified and compared to the number of complications
      observed during the same period with 435 classical iliac crest bone graft
      procedures performed for the same indications of treatment of fractures. Minor
      complications included superficial infections, superficial seromas, and minor
      haematomas. Major complications included herniation of abdominal contents through
      massive bone graft donor sites, vascular injuries, deep infections at the donor
      site, neurologic injuries, deep haematoma formation requiring surgical
      intervention or transfusion, and iliac wing fractures. RESULT: Bone marrow
      aspiration decreased significantly the number of complications as compared with
      harvesting classical iliac crest bone graft that was associated with significant
      morbidity. Adverse events were significantly lower (p < 0.01) in the 523
      procedures with bone marrow aspiration as compared with the 435 bone iliac crest
      piece harvesting. This was true for anaemia (16 cases versus 87 cases), for early
      pain (six versus 152), persistent pain (two versus 21), neuralgia (three versus
      11), minor complications (ten versus 56), and major complications (three cases
      versus 22 cases). CONCLUSION: In our series the number of complications with bone
      marrow aspiration was ten times less than the complications observed with the
      classical technique of bone piece harvesting from the iliac crest, and the
      complications were clearly less severe.

PMID- 24658875
TI  - Pharmacokinetics and preventive effects of platinum nanoparticles as reactive
      oxygen species scavengers on hepatic ischemia/reperfusion injury in mice.
AB  - Reactive oxygen species (ROS) are involved in the pathophysiology of
      ischemia/reperfusion injury. To protect mouse hepatocytes from
      ischemia/reperfusion injury, we prepared two different sizes of citric acid
      protected platinum nanoparticles (Pt-NPs), which exhibited ROS-scavenging
      activities and selective delivery to a specific type of liver cell. Small Pt-NPs
      (30 nm) reduced the superoxide anion, hydrogen peroxide, and hydroxyl radical
      levels in solution to a greater extent than did large Pt-NPs (106 nm). Large and
      small Pt-NPs predominantly accumulated in hepatic nonparenchymal cells after
      intravenous injection into mice. In a mouse model of ischemia/reperfusion injury,
      in which hepatic injury was induced by occluding the portal vein for 15 min
      followed by 6 h reperfusion, the increase in plasma alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) activities was inhibited by a bolus
      intravenous injection of either large or small Pt-NPs. However, small Pt-NPs
      inhibited the increase in these markers of hepatic injury to a greater extent
      than did large Pt-NPs. These results indicate that Pt-NPs can be used to prevent
      hepatic ischemia/reperfusion injury. To our knowledge, this is the first report
      demonstrating the pharmacokinetics and efficacy of Pt-NPs to prevent hepatic
      ischemia/reperfusion injury. 

PMID- 24658876
TI  - On the suppression of vaccination dissent.
AB  - Dissenters from the dominant views about vaccination sometimes are subject to
      adverse actions, including abusive comment, threats, formal
      complaints,censorship, and de registration, a phenomenon that can be called
      suppression of dissent. Three types of cases are examined: scientists and
      physicians; a high-profile researcher; and a citizen campaigner. Comparing the
      methods used in these different types of cases provides a preliminary framework
      for understanding the dynamics of suppression in terms of vulnerabilities.

PMID- 24658877
TI  - Higher cardiorespiratory fitness attenuates the risk of atherosclerosis
      associated with ADRB3 Trp64Arg polymorphism.
AB  - PURPOSE: beta3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated
      with atherogenic risk factors that include weight gain, insulin resistance, and
      diabetes. Habitual exercise brings higher cardiorespiratory fitness and results
      in the amelioration of atherosclerotic risk factors. However, the effects of
      cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of
      cardiovascular disease remain unclear. A cross-sectional investigation of 877
      Japanese men and women (18-75 years old) was performed to clarify the effects of
      cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism
      and risk of cardiovascular disease. METHOD: Common carotid intima-media thickness
      (ccIMT) and blood lipid profiles were assessed as surrogate markers of
      atherosclerosis. We measured peak oxygen uptake (VO(2peak)) during incremental
      cycle ergometer exercise testing. Subjects were divided into groups with high
      (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the
      median value of VO(2peak) for sex and decade. RESULTS: Levels of body fat,
      triglycerides, and plasma glucose were lower and high-density lipoprotein
      cholesterol levels and VO(2peak) were higher in High-Fit subjects than Low-Fit
      subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood
      lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the
      Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001);
      however, ADRB3 polymorphism had no effect in High-Fit subjects. CONCLUSION:
      Higher levels of cardiorespiratory fitness may attenuate the risk of
      atherosclerosis associated with ADRB3 Trp64Arg polymorphism.

PMID- 24658878
TI  - Pacing strategies during repeated maximal voluntary contractions.
AB  - PURPOSE: Pacing strategies have been reported to occur during continuous cyclical
      exercises. However, currently no studies have examined if pacing takes place
      during repeated maximal voluntary muscle contractions (MVCs). Accordingly, the
      purpose of this study was to examine if informing subjects on the number of MVCs
      they would perform would affect force and root mean squared electromyography
      (EMG), during similar fatiguing protocols. METHODS: Thirty well-trained male
      subjects completed three fatiguing protocols in a randomized order. In the
      control condition participants were informed they would perform 12 MVCs, and then
      completed all 12. In the unknown condition they were not told how many MVCs they
      would perform, but were stopped after 12. Lastly, in the deception condition they
      were initially told they would perform only 6 MVCs, but after the 6 contractions
      they were asked to perform a few more repetitions and were stopped after 12.
      RESULTS: Compared to the unknown condition, subjects demonstrated greater forces
      (p < 0.05, ES = 0.35-1.14, 2-7.5%) and biceps EMG (p < 0.05, ES = 0.6, 6%) in the
      deception condition during the first six MVCs. Additionally, under all conditions
      subjects applied greater forces in the last repetition (#12) relative to the
      previous one (#11) (p < 0.06, ES = 0.36-0.5, 2.8-3.8%). CONCLUSIONS: The
      anticipation of performing a certain number of MVCs led the subjects to utilize
      different pacing strategies. The results also question the assumption that
      subjects followed the instruction to exert maximal effort during repeated MVCs.

PMID- 24658880
TI  - Barley genetic variation: implications for crop improvement.
AB  - Genetic variation is crucial for successful barley improvement. Genomic
      technologies are improving dramatically and are providing access to the genetic
      diversity within this important crop species. Diverse collections of barley
      germplasm are being assembled and mined via genome-wide association studies and
      the identified variation can be linked to the barley sequence assembly.
      Introgression of favorable alleles via marker-assisted selection is now faster
      and more efficient due to the availability of single nucleotide polymorphism
      platforms. High-throughput genotyping is also making genomic selection an
      essential tool in modern barley breeding. Contemporary plant breeders now benefit
      from publicly available user-friendly databases providing genotypic and
      phenotypic information on large numbers of barley accessions. These resources
      facilitate access to allelic variation. In this review we explore how the most
      recent genomics and molecular breeding advances are changing breeding practices.
      The Coordinated Agricultural Projects (CAPs), Barley CAP and Triticeae CAP
      coupled with international collaborations, are discussed in detail as examples of
      a collaborative approach to exploit diverse germplasm resources for barley
      improvement. 

PMID- 24658879
TI  - Heterogeneity of breast cancer subtypes and survival among Hispanic women with
      invasive breast cancer in California.
AB  - There are limited data regarding breast cancer subtypes among Hispanic women. The
      current study assessed the distribution and prognosis of molecular subtypes
      defined by joint expression of the hormone receptors (HR; estrogen and
      progesterone) and human epidermal growth factor receptor 2 (HER2). Using
      California Cancer Registry data, we identified Hispanic women diagnosed with
      invasive breast cancer from 2005 to 2010. Breast cancer subtypes were defined as
      HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2- (triple negative). We estimated
      breast cancer subtype frequencies and used polytomous logistic regression, Kaplan
      Meier survival plots and Cox regression to examine differences in relation to
      demographic and clinical characteristics. Among 16,380 Hispanic women with breast
      cancer, HR+/HER- subtype was the most common (63 %), followed by triple negative
      (16 %), HR+/HER2+ (14 %), and HR-/HER2+ (8 %). Women in lower SES neighborhoods
      had greater risk of triple negative and HR-/HER2+ subtypes relative to HR+/HER2-
      (p < 0.05). Hispanic women with triple negative and HR-/HER2+ tumors experienced
      poorer survival than those with HR+/HER- tumors. Breast cancer-specific mortality
      increased with decreasing SES, relative to the highest SES quintile, from HR =
      1.38 for quintile 4 to HR = 1.76 for quintile 1 (lowest SES level). Our findings
      indicate that Hispanic women residing in low SES neighborhoods had significantly
      increased risk of developing and dying from HR- than HR+ breast cancers. Similar
      patterns of subtype frequency and prognosis among California Hispanic women and
      studies of other racial/ethnic groups underscore the need to better understand
      the impact of SES on risk factor exposures that increase the risk of breast
      cancer subtypes with poor prognosis.

PMID- 24658881
TI  - UHPLC-ESI-QTOF-MS-based metabolic profiling of Vicia faba L. (Fabaceae) seeds as
      a key strategy for characterization in foodomics.
AB  - Vicia faba (Fabaceae) is a popular food in many countries and a good source of
      nutrients. However, little is known about its phytochemical composition,
      specially referring to phenolic compounds. In the present work, the dietary
      metabolites from a hydro-methanolic extract of V. faba seeds were thoroughly
      characterized by a nontargeted analytical approach based on reversed-phase ultra
      HPLC (UHPLC) coupled to QTOF-MS. A total of 155 primary and secondary metabolites
      of various structural types were characterized: carbohydrates, amino acids,
      organic acids, alkaloids, terpenoids, jasmonates, and, mainly, polyphenols. Among
      the latter group, 73 compounds were characterized for the first time in this
      legume. In addition, 24 new structures, belonging to jasmonates and glycosylated
      N-containing compounds, were also proposed. Thus, this methodology could be
      implemented in foodomics as a characterization strategy to complement the
      knowledge of the phytochemical composition of vegetables.

PMID- 24658882
TI  - High flexion knee arthroplasty: the relationship between rotational angles and
      flexion angle after total knee arthroplasty.
AB  - The current patients required high flexion total knee arthroplasty (TKA). We
      hypothesized the patients who would get the high rotational angle just after TKA
      could gain high flexion knee 1 year after TKA. Sixty-three patients (average age:
      70.6 years) were examined. In order to examine between the intraoperative
      rotational angles and the gained flexion angles after TKA, the patients were
      divided into two groups: the H group (more than 120 degrees ) and the L groups
      (less than 120 degrees ) by the gained flexion angles. The relationship between
      the flexion angles at 1 year after surgery and the intraoperative rotational
      angle had no significant correlation. But the rotational angles in the L group
      tended to be higher than the ones in the H group, and at only 30 degrees , the L
      group gained significantly more rotational angle than the H group. These results
      might show that a tighter rotational stability induces a gain of higher flexion
      knee after TKA. 

PMID- 24658883
TI  - [Esthetic and functional improvement in proximal femoral focal deficiency with
      lacking hip joint by rotation plasty Winkelmann type BIII].
AB  - BACKGROUND: Proximal femoral focal deficiency (PFFD) types II and III (Pappas)
      have no femoral or only abortive femoral head development. Winkelmann published a
      case of one patient treated with a modification of rotation plasty by creating a
      new articulation after 180 degrees  rotation of the lower leg and insertion of
      the lateral tibial plateau into the deficient acetabulum. This article reports on
      three consecutive patients treated with this technique to validate this procedure
      and to consider this operation in selected patients. PATIENTS AND METHODS: At the
      time of rotation plasty the patients (2 boys and 1 girl) were aged between 5 and
      10 years. The observation period is between 5 and 9 years after surgery. All
      patients used an orthoprosthesis with full contact in the foot region and a shaft
      connecting the thigh. A hip basket and any additional walking support were not
      necessary (e.g. canes). They were all highly satisfied and would choose the same
      treatment again. CONCLUSION: Rotation plasty is a technically highly demanding
      procedure, especially in situations such as PFFD where the anatomy is distorted
      and structures such as blood vessels and nerves are too short. However, it is an
      option to improve the orthoprosthetic fitting functionally and esthetically.

PMID- 24658884
TI  - Conjugation versus rotation: good conjugation weakens the aggregation-induced
      emission effect of siloles.
AB  - Incorporation of polycyclic aromatic hydrocarbons into siloles enhances their
      light emission in solutions but lowers emission efficiency in the aggregated
      state. The competitive interaction between conjugation and rotation is thus
      studied. 

PMID- 24658885
TI  - A prognostic index for risk stratification for acute heart failure   and death in
      subjects with ischemic cardiomyopathy and cardiac   defibrillator.
AB  - To propose a clinical prognostic index for death and heart failure in patients
      with ischemic cardiomyopathy implanted with an ICD. This prospective study
      included 192 consecutive patients (age 68 +/- 10) recruited from 2004 to 2009 and
      implanted with an ICD for MADIT II criteria. All patients performed 24-h
      ambulatory blood pressure monitoring after discharge and common haematological
      samples. The prognostic index (PI) was built according to the formula: 120 - age
      + mean 24 h systolic blood pressure--(creatinine 9 10). Other variables were
      assessed: EF, haemoglobin concentration, mean 24 h heart rate and diastolic blood
      pressure, sodium level, pacing mode and diabetes. Non-arrhythmic cardiac death
      and new hospitalizations for heart failure during 1-year follow-up were the
      combined end point. A total of 48 events (25%) occurred during the follow-up: 7
      cardiac deaths and 41 hospitalizations for acute heart failure. Cox proportional
      hazards model showed that PI was the only predictor of events (HR = 0.96; CI 95%
      0.944-0.976, p < 0.0001). ROC curve showed that PI best cut-off was 144, with AUC
      0.79, p < 0.0001; sensitivity 77%, specificity 74%, positive predictive value
      50%, negative predictive value 90%. PI was predictive of events in a clinical
      setting where EF had no predictive value. PI works according to the rule ''the
      lower the worse''. The high negative predictive value (90%) of PI allows to
      identify subjects at lower risk for death and heart failure. PI can be a
      practical tool to stratify risk in ischemic cardiomyopathy.

PMID- 24658886
TI  - Prediction of left atrial thrombi in patients with atrial   tachyarrhythmias
      during warfarin administration: retrospective   study in Hyogo College of
      Medicine.
AB  - Some patients experience a left atrial thrombus (LAT) in spite of taking
      warfarin. We aimed to clarify the characteristics of patients with LAT during
      warfarin administration and investigated whether the CHADS2 or CHA2DS2-VASc
      scores are useful predictors of LAT. We studied 230 patients (169 males, age 65
      +/- 10 years) who underwent transesophageal echocardiography (TEE) prior to
      cardioversion or catheter ablation of atrial tachyarrhythmias between 2008 and
      2012. All patients were taking oral warfarin. LAT was detected in 19 patients
      (8.3%) using TEE. LAT was significantly associated with the presence of
      hypertension (P = 0.0035), prior congestive heart failure (P < 0.0001),
      structural heart disease (P = 0.0012), persistent arrhythmias (P < 0.0001), the
      absence of SR during TEE (P = 0.0070), left ventricular ejection fraction (P <
      0.0001), left atrial diameter (P = 0.0015), left ventricular dimension during end
      diastole (P = 0.0215), left ventricular hypertrophy (LVH; P < 0.0001), and the
      E/e' ratio (P = 0.0074). A multivariate analysis showed that LVH (P = 0.0065, OR
      5.591, 95% CI 1.618-19.316) and persistent arrhythmia (P = 0.0364, OR 12.121, 95%
      CI 1.171-125.451) were independently associated with LAT. Moreover, the mean
      CHADS2 (2.3 +/- 0.9 vs. 1.4 +/- 1.2) and CHA2DS2-VASc scores (3.8 +/- 1.2 vs. 2.8
      +/- 1.7) were higher in the patients with than without LAT. However, a
      multivariate analysis showed that the CHADS2/CHA2DS2-VASc scores did not
      associate with LAT. LVH and persistent arrhythmia may be useful for predicting
      LAT in patients with atrial tachyarrhythmias.

PMID- 24658887
TI  - Occupational medicine and environmental health. Introduction to the first issue
      of 2014. Editorial.

PMID- 24658888
TI  - Interstitial pneumonitis after acetylene welding: a case report.
AB  - Acetylene is a colorless gas commonly used for welding. It acts mainly as a
      simple asphyxiant. In this paper, however, we present a patient who developed a
      severe interstitial pneumonitis after acetylene exposure during aluminum welding.
      A 44-year old man was welding with acetylene, argon and aluminum electrode sticks
      in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea
      appeared and 22 h later he was admitted at the Emergency Department due to severe
      respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse
      interstitial infiltration. Pulmonary function and gas diffusion tests revealed a
      severe restriction (55% of predictive volume) and impaired diffusion capacity
      (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and
      high-dose systemic corticosteroid methylprednisolone and inhalatory
      corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the
      lungs showed a diffuse patchy ground-glass opacity with no signs of small airway
      disease associated with interstitial pneumonitis. Corticosteroid therapy was
      continued for the next 8 weeks gradually reducing the doses. The patient's follow
      up did not show any deterioration of respiratory function. In conclusion,
      acetylene welding might result in severe toxic interstitial pneumonitis that
      improves after an early systemic and inhalatory corticosteroid therapy. 

PMID- 24658890
TI  - Supercritical CO2 induces marked changes in membrane phospholipids composition in
      Escherichia coli K12.
AB  - Supercritical carbon dioxide (SC-CO2) treatment is one of the most promising
      alternative techniques for pasteurization of both liquid and solid food products.
      The inhibitory effect of SC-CO2 on bacterial growth has been investigated in
      different species, but the precise mechanism of action remains unknown. Membrane
      permeabilization has been proposed to be the first event in SC-CO2-mediated
      inactivation. Flow cytometry, high performance liquid chromatography-electrospray
      ionization-mass spectrometry and NMR analyses were performed to investigate the
      effect of SC-CO2 treatment on membrane lipid profile and membrane permeability in
      Escherichia coli K12. After 15 min of SC-CO2 treatment at 120 bar and 35  degrees
      C, the majority of bacterial cells dissipated their membrane potential (95 %) and
      lost membrane integrity, as 81 % become partially permeabilized and 18 % fully
      permeabilized. Membrane permeabilization was associated with a 20 % decrease in
      bacterial biovolume and to a strong (>50 %) reduction in phosphatidylglycerol
      (PG) membrane lipids, without altering the fatty acid composition and the degree
      of unsaturation of acyl chains. PGs are thought to play an important role in
      membrane stability, by reducing motion of phosphatidylethanolamine (PE) along the
      membrane bilayer, therefore promoting the formation of inter-lipid hydrogen
      bonds. In addition, the decrease in intracellular pH induced by SC-CO2 likely
      alters the chemical properties of phospholipids and the PE/PG ratio. Biophysical
      effects of SC-CO2 thus cause a strong perturbation of membrane architecture in E.
      coli, and such alterations are likely associated with its strong inactivation
      effect.

PMID- 24658889
TI  - Tonoplast lipid composition and proton pump of pineapple fruit during low
      temperature storage and blackheart development.
AB  - Vacuole represents a major storage organelle playing vital roles in pH
      homoeostasis and cellular detoxification. The chemical and functional properties
      of tonoplast in response to chilling temperature and their roles in chilling
      injury are largely unknown. In the current study, lipid composition of tonoplast
      and the activities of two vacuolar proton pumps, H?-ATPase (V-ATPase) and H?
      pyrophosphatase (V-PPase), were investigated in accordance with the development
      of blackheart, a form of chilling injury in pineapple fruit (Ananas comosus).
      Chilling temperature at 10  degrees C for 1 week induced irreversible blackheart
      injury in concurrence with a substantial decrease in V-ATPase activity. By
      contrast, the activity was increased after 1 week at 25  degrees C. The activity
      of V-PPase was not changed under both temperatures. Level of total phospholipids
      of tonoplast decreased at 10  degrees C, but increased at 25  degrees C. There
      was no change at the level of total glycolipids under both temperatures. Thus,
      low temperature increased the ratio of total glycolipids vs. total phospholipids
      of tonoplast. Phosphatidylcholine and phosphatidylethanolamine were the
      predominant phospholipids of tonoplast. Low temperature increased the relative
      level of phosphatidic acid but decreased the percentage of both
      phosphatidylcholine and phosphatidylethanolamine. Unsaturated fatty acids
      accounted for over 60 % of the total tonoplast fatty acids, with C18:1 and C18:2
      being predominant. Low temperature significantly decreased the percentage of
      C18:3. Modification of membrane lipid composition and its effect on the
      functional property of tonoplast at low temperature were discussed in correlation
      with their roles in the development of chilling injury in pineapple fruit.

PMID- 24658892
TI  - Confronting ethical permissibility in animal research:  rejecting a common
      assumption and extending  a principle of justice.
AB  - A common assumption in the selection of nonhuman animal subjects for research and
      the approval of research is that, if the risks of a procedure are too great for
      humans, and if there is a so-called scientific necessity, then it is permissible
      to use nonhuman animal subjects. I reject the common assumption as neglecting the
      central ethical issue of the permissibility of using nonhuman animal subjects and
      as being inconsistent with the principle of justice used in human subjects
      research ethics. This principle requires that certain classes of individuals not
      be subjected to a disproportionate share of the burdens or risks of research. I
      argue for an extension of this principle to nonhuman animal research and show
      that a prima facie violation of the principle occurs because nonhuman animals
      bear an overwhelmingly disproportionate share of the risks of research without
      sufficient justification or reciprocal benefit.

PMID- 24658891
TI  - Correspondence between flowers and leaves in terpenoid indole alkaloid metabolism
      of the phytoplasma-infected Catharanthus roseus plants.
AB  - Several plants of Catharanthus roseus cv 'leafless inflorescence (lli)' showing
      phenotype of phytoplasma infection were observed for symptoms of early flowering,
      virescence, phyllody, and apical clustering of branches. Symptomatic plants were
      studied for the presence/absence and identity of phytoplasma in flowers.
      Transcription levels of several genes involved in plants' metabolism and
      development, accumulation of pharmaceutically important terpenoid indole
      alkaloids in flowers and leaves and variation in the root-associated microbial
      flora were examined. The expression profile of 12 genes studied was semi
      quantitatively similar in control leaves and phytoplasma-infected leaves and
      flowers, in agreement with the symptoms of virescence and phyllody in phytoplasma
      infected plants. The flowers of phytoplasma-infected plants possessed the TIA
      profile of leaves and accumulated catharanthine, vindoline, and vincristine and
      vinblastine in higher concentrations than leaves. The roots of the infected
      plants displayed lower microbial diversity than those of normal plants. In
      conclusion, phytoplasma affected the biology of C. roseus lli plants
      multifariously, it reduced the differences between the metabolite accumulates of
      the leaves and flowers and restrict the microbial diversity of rhizosphere.

PMID- 24658893
TI  - Differences in biological features of breast cancer between Caucasian (Italian)
      and African (Tanzanian) populations.
AB  - Information on hormone receptor and human epidermal growth factor receptor-2
      (HER2) expression in breast cancer is acknowledged as mandatory for prognostic
      stratification and treatment planning. Data on the biological features of African
      breast cancers are poor. We decided to compare histopathological and biomolecular
      characteristics (estrogen and progesterone receptor-ER, PgR, and HER2) of
      Tanzanian and Italian breast cancers. Differences in proliferating index and
      androgen receptor (AR) expression in triple-negative patients from the two case
      series were also assessed. Of the 103 consecutive patients seen at the Bugando
      Medical Center (Mwanza, Tanzania) from 2003 to 2010, who underwent biopsy or
      surgical resection of primary breast cancer, 69 patients had tissue samples that
      were evaluable for estrogen receptor (ER), progesterone receptor (PgR), and HER2.
      Histopathological assessment and biomolecular determinations were performed at
      the Cancer Institute of Romagna (IRST IRCCS, Meldola, Italy). Caucasian breast
      cancers were randomly extracted from an electronic database and matched (1:2
      ratio) for year of diagnosis and age at diagnosis. Median age of both populations
      was 51 years (range 27-84). With respect to Caucasian tumors, Tanzanian breast
      cancers at diagnosis more frequently showed high histological grade (mainly grade
      3) (P = 0.03), advanced clinical stage (III or IV) (P?0.001), ER negativity (52.2
      %, P?0.001) and high proliferation (P = 0.0002). Triple-negative tumors were over
      represented in Tanzanian women. AR was positive in 38.5 and 38 %of triple
      negative Tanzanian and Italian breast cancers, respectively. Our results show
      that histopathological and biomolecular characteristics in Tanzanian and Italian
      breast cancers differ substantially. The high frequency of poorly differentiated,
      ER-negative, highly proliferating tumors, together with advanced stage at
      presentation, could be considered as the main prognostic factors linked to the
      high mortality rates for breast cancer in the African population.

PMID- 24658894
TI  - Using the Autism Detection in Early Childhood (ADEC) and Childhood Autism Rating
      Scales (CARS) to predict long term outcomes in children with autism spectrum
      disorders.
AB  - This study evaluated the predictive validity of the Autism Detection in Early
      Childhood (ADEC; Young, Autism detection in early childhood: ADEC. Australian
      Council of Educational Research, Camberwell, VIC 2007) and a well-established
      screening tool, the Childhood Autism Rating Scale (CARS; Schopler et al. The
      childhood autism rating scale (CARS). Western Psychological Services, Los Angeles
      1988), for long term outcomes of children with ASD engaged in an early
      intervention program. Participants were 55 children (44 male, 11 female) aged 19
      42 months (M = 33.5, SD = 5.6) at initial assessment who were followed up 2 and 6
      years after their initial assessment. The ADEC and the CARS performed similarly
      when predicting long term outcomes such as clinical diagnostic outcome and
      overall adaptive functioning level. However, only the ADEC score was
      significantly correlated with ASD symptom severity at the 6-year follow up.
      Although these findings need to be replicated with additional and larger samples,
      this study extends our understanding of the psychometric properties of both the
      ADEC and the CARS.

PMID- 24658895
TI  - A comparison of percutaneous dilatational tracheostomy versus conventional
      surgical tracheostomy.
AB  - BACKGROUND: Percutaneous dilatational tracheostomy (PDT) and surgical
      tracheostomy (ST) are widely accepted techniques and frequently performed in
      clinical practice. We compared PDT with ST tracheostomies in view of the benefits
      and drawbacks, time of duration, indication and complication rate of the
      respective procedures. METHODS: The evaluation was based on data from 378
      tracheostomies. 209 of these tracheostomies were performed at bedside as PDT in
      the intensive care unit. These were compared to 169 ST tracheostomies performed
      in the operating room. All interventions were performed by the same team of
      surgeons or intensivists, however, at different training levels. RESULTS: The
      mean duration of the operation was shorter for PDT than for ST (18.2 +/- 10 min
      versus 38.2 +/- 14.2 min, p = < 0.001). The PDT was a simpler procedure and
      performed predominantly by physicians in postgraduate training. The rate of
      complications was low in both groups (8.6 % PDT, 8.3 % ST, p = 0.909).
      CONCLUSION: Although both interventions are safe and achieve comparable results,
      PDT can be applied in a shorter time. PDT is easier to perform and seems
      particularly suitable for physicians in postgraduate training.

PMID- 24658896
TI  - [Therapy adherence in bronchial asthma patients: Healthcare under everyday
      conditions in pulmonological practices].
AB  - In the present study, patients with asthma were interviewed with regard to their
      treatment adherence. It was shown that adherence is significantly influenced by
      age, occupation, quality of information about the disease and interest of the
      patient in disease, mode of action and use of the inhalation device. Younger,
      working patients who do not feel "completely adequately" informed are more likely
      to be not-adherent. Each aspect should be noted separately.The characterization
      enables forming target groups for appropriate counselling initiatives in
      pulmonology practice and allows the effectiveness of the measures to be examined.
      The results confirm the importance of doctor/patient communication for achieving
      a high level of adherence and thus therapeutic success.It is suggested that, in
      addition to questionnaires already in use, asthma patients should be given the
      following questions in writing during routine monitoring of therapy; based on the
      results of the survey, the extent of advice necessary can be determined -Do you
      feel sufficiently informed about your illness? -Do you feel sufficiently informed
      about the effect of the drug therapy? -Do you feel sufficiently informed about
      the handling of the inhalation drugs? -Are you satisfied with the handling of
      your inhalation medication? The following options to answer the questions should
      be available: completely - mainly - somewhat - not at all. There were significant
      differences in adherence between patients who were completely satisfied with the
      handling of their device and those that were not. However, there was no
      significant difference between the devices. Therefore, the same therapy adherence
      can be predicted for all devices when the device is suitable for the patient and
      also provides complete satisfaction in handling. Since it is the subjective
      perception of patients, the data show significant differences between study
      centres. These were mirrored in a blind benchmark to stimulate improvements.

PMID- 24658897
TI  - Efficacy and safety of daptomycin in patients with renal impairment: a
      multicenter retrospective analysis.
AB  - STUDY OBJECTIVE: Daptomycin is a therapeutic option for patients with underlying
      renal insufficiency who are vulnerable to nephrotoxicity from vancomycin. We
      evaluated the efficacy and safety of daptomycin in patients with renal
      impairment. DESIGN: Multicenter, retrospective, observational, case series
      analysis. SETTING: Two academic medical centers. PATIENTS: One hundred and sixty
      adults with creatinine clearance (Clcr ) of 50 ml/minute or less who received
      daptomycin for at least 72 hours for complicated Gram-positive infections from
      2008-2011. MEASUREMENTS AND MAIN METHODS: Clinical and microbiologic outcomes
      were assessed at the end of daptomycin therapy. Safety evaluations were
      documented for all patients, and when available, creatine phosphokinase (CPK)
      levels were recorded. Thirty-eight (23.8%) patients were on hemodialysis, and 122
      (76.3%) had a decreased baseline renal clearance not requiring hemodialysis with
      a median interquartile range (IQR) Clcr of 32.4 ml/minute (24.2-40.4 ml/min). The
      median (IQR) daptomycin dose was 6.0 mg/kg (5.8-7.8 mg/kg) administered every 24
      hours in 68 patients (42.5%) and every 48 hours in 92 patients (57.5%).
      Daptomycin success, including cure or improvement, (Cure: signs and symptoms
      resolved and no additional antibiotic therapy required, or infection cleared with
      negative cultures reported at the end of daptomycin therapy; Improvement: partial
      resolution of signs and symptoms and additional antibiotic therapy necessary at
      the end of daptomycin therapy) was achieved in 128 of 160 (80.0%) patients at the
      end of therapy. Methicillin-resistant Staphylococcus aureus (MRSA) was the most
      common pathogen (45%) isolated. The most frequent reason for using daptomycin was
      due to vancomycin-associated nephrotoxicity (20%). Daptomycin therapy was
      discontinued in six patients (3.8%) because of elevated CPK (median time to
      onset, 11.5 days). Loss of daptomycin susceptibility occurred in two patients
      with complex endovascular infections who were on hemodialysis. CONCLUSIONS:
      Daptomycin demonstrated clinical and microbiologic success rates comparable with
      prior studies. Discontinuation of therapy because of elevated CPK levels may have
      been avoided in some patients with adjustment to every 48-hour dosing for Clcr
      less than 30 ml/minute. The relatively early time to onset suggests the need for
      CPK monitoring more frequently than once/week in renally impaired patients
      receiving daptomycin. The treatment of bacteremia in patients with renal
      insufficiency warrants further study.

PMID- 24658898
TI  - Reply to letter to the editor: Tourniquet use during cementation only during
      total knee arthroplasty: a randomized trial.

PMID- 24658899
TI  - Letter to the editor: Labral injuries of the hip in rowers.

PMID- 24658900
TI  - Is circumferential minimally invasive surgery effective in the treatment of
      moderate adult idiopathic scoliosis?
AB  - BACKGROUND: Outcomes for minimally invasive scoliosis correction surgery have
      been reported for mild adult scoliosis. Larger curves historically have been
      treated with open surgical procedures including facet resections or posterior
      column osteotomies, which have been associated with high-volume blood loss.
      Further, minimally invasive techniques have been largely reported in the setting
      of degenerative scoliosis. QUESTIONS/PURPOSES: We describe the effects of
      circumferential minimally invasive surgery (cMIS) for moderate to severe
      scoliosis in terms of (1) operative time and blood loss, (2) overall health and
      disease-specific patient-reported outcomes, (3) deformity correction and fusion
      rate, and (4) frequency and types of complications. METHODS: Between January 2007
      and January 2012, we performed 50 cMIS adult idiopathic scoliosis corrections in
      patients with a Cobb angle of greater than 30 degrees  but less than 75 degrees 
      who did not have prior thoracolumbar fusion surgery; this series represented all
      patients we treated surgically during that time meeting those indications. Our
      general indications for this approach during that period were increasing back
      pain unresponsive to nonoperative therapy with cosmetic and radiographic
      worsening of curves. Surgical times and estimated blood loss were recorded.
      Functional clinical outcomes including VAS pain score, Oswestry Disability Index
      (ODI), and SF-36 were recorded preoperatively and postoperatively. Patients'
      deformity correction was assessed on pre- and postoperative 36-inch (91-cm)
      standing films and fusion was assessed on CT scan. Minimum followup was 24 months
      (mean, 48 months; range, 24-77 months). RESULTS: Mean blood loss was 613 mL for
      one-stage surgery and 763 mL for two-stage surgery. Mean operative time was 351
      minutes for one-stage surgery and 482 minutes for two-stage surgery. At last
      followup, mean VAS and ODI scores decreased from 5.7 and 44 preoperatively to 2.9
      and 22 (p < 0.001 and 0.03, respectively) and mean SF-36 score increased from 48
      preoperatively to 74 (p = 0.026). Mean Cobb angle and sagittal vertical axis
      decreased from 42 degrees  and 51 mm preoperatively to 16 degrees  and 27 mm
      postoperatively (both p < 0.001). An 88% fusion rate was confirmed on CT scan.
      Perioperative complications occurred in 11 of the 50 patients (22%), with delayed
      complications needing further surgery in 10 more patients at last followup.
      CONCLUSIONS: cMIS provides for good clinical and radiographic outcomes for
      moderate (30 degrees -75 degrees ) adult idiopathic scoliosis. Patients
      undergoing cMIS should be carefully selected to avoid fixed, rigid deformities
      and a preoperative sagittal vertical axis of greater than 10 cm; surgeons should
      consider alternative techniques in those patients. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24658901
TI  - What is the frequency of vascular injury after knee dislocation?
AB  - BACKGROUND: Vascular injury secondary to an acute knee dislocation is a known
      complication. However, there exist wide discrepancies in the reported rate of
      vascular injury in this setting. QUESTIONS/PURPOSES: Using a large private
      insurance database, we determined the frequency of vascular injury in knee
      dislocations across year of diagnosis, age, sex, and US geographic region and the
      proportion of these injuries requiring surgical repair. METHODS: The PearlDiver
      database, which contains records from 11 million orthopaedic patients, was
      searched using ICD-9 diagnostic codes for all knee dislocation events from 2004
      to 2009. Within this subset, we identified which knee dislocations had an
      associated vascular injury ICD-9 code. Patients were stratified by year of
      diagnosis, age, sex, and US geographic region, and Current Procedural Terminology
      codes were used to identify the subset of patients with vascular injury requiring
      surgical repair. Differences in frequency across demographic groups and over time
      were analyzed with Poisson regression analysis. RESULTS: Among the 8050 limbs
      with knee dislocation identified over the study period, 267 had a concomitant
      vascular injury for an overall frequency of 3.3%. Males were found to have an
      increased risk of vascular injury compared to females (odds ratio = 2.59, p <
      0.001). Additionally, patients aged 20 to 39 years had a higher risk of vascular
      injury when compared to those aged 0 to 19 years (odds ratio = 1.93, p = 0.001),
      40 to 59 years (odds ratio = 1.57, p = 0.014), and 60 years or older (odds ratio
      = 2.81, p = 0.036). There were no differences in vascular injury frequency across
      US geographic regions or diagnosis year. Thirty-four of the 267 cases of vascular
      injury (13%) underwent surgical treatment. CONCLUSIONS: This is the largest
      study, to our knowledge, that analyzes the proportion of knee dislocations that
      result in vascular injury. Our data suggest that there is a lower frequency of
      vascular injury associated with knee dislocation and a lower proportion of
      vascular injuries undergoing surgical treatment than previously reported. These
      findings may support a more selective angiography protocol to screen for vascular
      injury, rather than performing this invasive diagnostic test on all knee
      dislocations, as has been done historically. Future large-scale and prospective
      studies should analyze factors that may predispose to vascular injuries after
      knee dislocation and determine which patients should be screened for vascular
      injury after knee dislocation. LEVEL OF EVIDENCE: Level IV, prognostic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24658902
TI  - The effect of resident participation on short-term outcomes after orthopaedic
      surgery.
AB  - BACKGROUND: The influence of resident involvement on short-term outcomes after
      orthopaedic surgery is mostly unknown. QUESTIONS/PURPOSES: The purposes of our
      study were to examine the effects of resident involvement in surgical cases on
      short-term morbidity, mortality, operating time, hospital length of stay, and
      reoperation rate and to analyze these parameters by level of training. METHODS:
      The 2005-2011 American College of Surgeons National Surgical Quality Improvement
      Program data set was queried using Current Procedural Terminology codes for
      66,817 cases across six orthopaedic procedural domains: 28,686 primary total
      joint arthroplasties (TJAs), 2412 revision TJAs, 16,832 basic and 5916 advanced
      arthroscopies, 8221 lower extremity traumas, and 4750 spine arthrodeses
      (fusions). Bivariate and multivariate logistic regression and propensity scores
      were used to build models of risk adjustment. We compared the morbidity and
      mortality rates, length of operating time, hospital length of stay, and
      reoperation rate for cases with or without resident involvement. For cases with
      resident participation, we analyzed the same parameters by training level.
      RESULTS: Resident participation was associated with higher morbidity in TJAs
      (odds ratio [OR], 1.6; range, 1.4-1.9), lower extremity trauma (OR, 1.3; range,
      1.2-1.5), and fusion (OR, 1.4; range, 1.2-1.7) after adjustment. However,
      resident involvement was not associated with increased mortality. Operative time
      was greater (all p < 0.001) with resident involvement in all procedural domains.
      Longer hospital length of stay was associated with resident participation in
      lower extremity trauma (p < 0.001) and fusion cases (p = 0.003), but resident
      participation did not affect length of stay in other domains. Resident
      involvement was associated with greater 30-day reoperation rates for cases of
      lower extremity trauma (p = 0.041) and fusion (p < 0.001). Level of resident
      training did not consistently influence surgical outcomes. CONCLUSIONS: Results
      of our study suggest resident involvement in surgical procedures is not
      associated with increased short-term major morbidity and mortality after select
      cases in orthopaedic surgery. Findings of longer operating times and differences
      in minor morbidity should lead to future initiatives to provide resident surgical
      skills training and improve perioperative efficiency in the academic setting.
      LEVEL OF EVIDENCE: Level II, prognostic study. See the Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24658903
TI  - Sonication of antibiotic spacers predicts failure during two-stage revision for
      prosthetic knee and hip infections.
AB  - BACKGROUND: Periprosthetic joint infection is a leading cause of failure after
      two-stage reimplantation. One cause of relapse may be persistent subclinical
      infection. Difficulty exists in detecting biofilm-forming infections. Sonication
      disrupts biofilm and has led to higher rates of positive intraoperative cultures.
      QUESTIONS/PURPOSES: Our aims in this study were to determine (1) if sonication
      results were predictive of failure, including reinfection, at 2-year followup;
      and (2) whether sonication of antibiotic spacers at the time of reimplantation
      improves sensitivity of intraoperative cultures. METHODS: We prospectively
      followed 36 consecutive patients undergoing two-stage reimplantation for
      periprosthetic hip or knee infection. Minimum followup was 19 months (mean, 29.9
      months; range, 19-38 months). Results of intraoperative cultures and sonicated
      antibiotic spacers were analyzed. RESULTS: Positive sonication results were
      predictive of failure as defined by reinfection at 2-year followup. Among the 18
      patients who had positive sonication results, reinfection developed in nine
      patients (50%) compared with two of 18 patients (11%) with negative sonication
      results (odds ratio, 8.0; 95% CI, 1.2-69.0). Sonication of antibiotic spacers
      improved the sensitivity of intraoperative cultures from 45% to 82%. [corrected].
      CONCLUSIONS: Sonication of antibiotic spacers appears to be useful in predicting
      failure attributable to recurrent infection after two-stage reimplantation. For
      patients with positive sonication cultures during reimplantation, more aggressive
      antimicrobial treatment may be indicated after reimplantation. LEVEL OF EVIDENCE:
      Level III, diagnostic study. See the Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24658904
TI  - Peroral endoscopic myotomy (POEM): feasible as reoperation following Heller
      myotomy.
AB  - PURPOSE: The purpose of this study was to demonstrate the feasibility of
      performing peroral endoscopic myotomy (POEM) in the management of recurrent
      achalasia after failed myotomy. METHODS: Eight patients presented to our
      institution between October 2010 and June 2013 with recurrent/persistent symptoms
      after prior laparoscopic Heller myotomy. Three patients underwent redo
      laparoscopic Heller myotomy, and five patients consented to redo myotomy with
      POEM. RESULTS: Demographics were similar between the groups with exception of age
      (POEM 69.5 vs. laparoscopic Heller myotomy (LHM) 34.5, p = 0.003). Preoperative
      Eckardt scores, motility, and prior interventions were not significantly
      different. Three patients who underwent POEM and two who underwent laparoscopic
      Heller myotomy had prior fundoplication. There was one perforation identified
      after laparoscopic Heller myotomy and one patient with persistent subcutaneous
      emphysema after POEM. Both POEM and laparoscopic Heller myotomy demonstrated
      significant improvement in symptoms and Eckardt scores at average follow-up of
      approximately 5 months (p < 0.05). CONCLUSION: POEM is a feasible option for
      patients after failed myotomy even in the presence of prior fundoplication. The
      procedure can be performed safely using a similar technique as for primary
      myotomy with the exception of creating the myotomy laterally along the right side
      of the esophagus and lesser curvature avoiding the previous anterior myotomy.

PMID- 24658905
TI  - New insight into reactive ductular cells of biliary atresia provided  by
      pathological assessment of SOX9.
AB  - BACKGROUND: Biliary atresia (BA) patients may survive until adolescence after
      effective Kasai procedure (KP). If liver fibrosis progresses even after
      successful KP, liver transplantation (LTx) is inevitable. Elucidation of its
      cause and pathophysiology would open the possibility of treating these patients
      by non-invasive management. SOX9 is a transcription factor that regulates bile
      duct development and contributes to liver regeneration and fibrosis. To elucidate
      the role of SOX9 in BA liver, we investigated the SOX9 expression pattern.
      METHOD: Immunostaining with anti-SOX9 antibody was done on hepatic specimens
      obtained at the time of KP or LTx. We analyzed the association of SOX9 expression
      with clinical data. RESULTS: In BA livers, SOX9 was expressed in reactive
      ductular cells (RDCs), mostly with a nuclear-dominant pattern. SOX9 was also
      ectopically expressed in hepatocytes, which was more conspicuous at the timing of
      KP than LTx. SOX9 expression level was significantly correlated with age (days)
      at which KP was performed, AST and WBC count. CONCLUSIONS: SOX9 may contribute to
      RDC formation in BA patients, by affecting both RDCs and hepatocytes. SOX9 could
      be a key molecule to understand the mechanism of RDC formation, and this
      understanding would provide a therapeutic strategy for effective treatment of BA.

PMID- 24658906
TI  - Proper screening for sudden cardiac death in the young athlete.

PMID- 24658907
TI  - Feasibility of automated appointment reminders using email.

PMID- 24658908
TI  - Variability of the institutional review board process within a national research
      network.
AB  - OBJECTIVE: To determine the variability of the institutional review board (IRB)
      process for a minimal risk multicenter study. METHODS: Participants included 24
      Continuity Research Network (CORNET) sites of the Academic Pediatric Association
      that participated in a cross-sectional study. Each site obtained individual
      institutional IRB approval. An anonymous questionnaire went to site investigators
      about the IRB process at their institution. RESULTS: Twenty-two of 24 sites (92%)
      responded. Preparation time ranged from 1 to 20 hours, mean of 7.1 hours.
      Individuals submitting <=3 IRB applications/year required more time for
      completion than those submitting >3/year (P < .05). Thirteen of 22 (59%) study
      sites received approval with "exempt" status, and 6 (27%) approved as "expedited"
      studies. CONCLUSIONS: IRB experiences were highly variable across study sites.
      These findings indicate that multicenter research projects should anticipate
      barriers to timely study implementation. Improved IRB standardization or
      centralization for multicenter clinical studies would facilitate this type of
      practice-based clinical research.

PMID- 24658909
TI  - Leukocytosis in an infant with Down syndrome.

PMID- 24658910
TI  - Improving developmental screening among pediatricians in New Mexico: findings
      from the developmental screening initiative.
AB  - BACKGROUND: Seven pediatric primary care practices participated in New Mexico's
      Developmental Screening Initiative in a year-long quality improvement project
      with the goal of implementing standardized developmental screening tools.
      METHODS: The initiative utilized a learning collaborative approach and the Model
      for Improvement to promote best practice about developmental screening outlined
      by the American Academy of Pediatrics. Also, the project emphasized interagency
      collaboration to improve communication between medical providers and state and
      community agencies that provide services to children with developmental delays.
      RESULTS: A total of 1139 medical records were reviewed by the 7 practices, at 5
      intervals during the intervention. At baseline, there were dramatic differences
      among the practices, with some not engaged in screening at all. Overall, the use
      of standardized developmental screening increased from 27% at baseline to 92% at
      the end of the project.

PMID- 24658911
TI  - B7-H4 downregulation induces mitochondrial dysfunction and enhances doxorubicin
      sensitivity via the cAMP/CREB/PGC1-alpha signaling pathway in HeLa cells.
AB  - B7-H4 is a B7 family coregulatory protein that inhibits T cell-mediated immunity.
      B7-H4 is overexpressed in various cancers; however, the functional role of B7-H4
      in cancer metabolism is poorly understood. Because mitochondria play pivotal
      roles in development, proliferation, and death of cancer cells, we investigated
      molecular and functional alterations of mitochondria in B7-H4-depleted HeLa
      cells. In a human study, overexpression of B7-H4 was confirmed in the cervices of
      adenocarcinoma patients (n = 3) compared to noncancer patients (n = 3). In the
      cell line model, B7-H4 depletion was performed by transfection with small
      interfering RNA (siRNA). B7-H4 depletion suppressed oxygen consumption rate, ATP
      production, and mitochondrial membrane potential and mass and increased reactive
      oxygen species production. In particular, electron transport complex III activity
      was significantly impaired in siB7-H4-treated cells. Coincidently, depletion of
      B7-H4 suppressed major mitochondrial regulators (peroxisome proliferator
      activated receptor gamma coactivator 1-alpha [PGC1-alpha] and mitochondrial
      transcription factor A), a component of oxidative phosphorylation (ubiquinol
      cytochrome c reductase core protein 1), and an antiapoptosis protein (Bcl-XL).
      Mitochondrial dysfunction in siRNA-treated cells significantly augmented
      oxidative stress, which strongly activated the JNK/P38/caspase axis in the
      presence of doxorubicin, resulting in increased apoptotic cell death.
      Investigating the mechanism of B7-H4-mediated mitochondrial modulation, we found
      that B7-H4 depletion significantly downregulated the cAMP/cAMP response element
      binding protein/PGC1-alpha signaling pathway. Based on these findings, we
      conclude that B7-H4 has a role in the regulation of mitochondrial function, which
      is closely related to cancer cell physiology and drug sensitivity.

PMID- 24658913
TI  - Airway management in the critically ill.
AB  - Successful first attempt intubation of the critically ill patient is of extreme
      importance. While these patients are anatomically and physiologically
      complicated, making intubation particularly risky, several important steps have
      recently been shown to improve the chances of a safe first attempt success.
      Proper evaluation, planning, positioning, preoxygenation, and in select patients
      the use of a neuromuscular blocking agent have all been shown to be useful for
      minimizing the difficult intubation and intubation- related complications.
      Additionally, although there is significant controversy regarding video
      laryngoscopy, the use of a video laryngoscope as the primary method of intubation
      has been shown in all cases to be at least as good as, and often more successful
      than, direct laryngoscopy.

PMID- 24658912
TI  - Characteristics and prognosis of sudden cardiac death in Greater Paris:
      population-based approach from the Paris Sudden Death Expertise Center (Paris
      SDEC).
AB  - PURPOSE: Sudden cardiac death (SCD) is a major public health concern, but data
      regarding epidemiology of this disease in Western European countries are
      outdated. This study reports the first results from a large registry of SCD.
      METHODS: A population-based registry was established in May 2011 using multiple
      sources to collect every case of SCD in Paris and its suburbs, covering a
      population of 6.6 million. Utstein variables were recorded. Pre-hospital and in
      hospital data were considered, and the main outcome was survival at hospital
      discharge. Neurologic status at discharge was established as well. RESULTS: Of
      the 6,165 cases of SCD recorded over 2 years, 3,816 had a resuscitation attempt
      and represent the study population. Most patients were male (69%), the SCD
      occurred at home (72%) with bystanders in 80% of cases, and cardiopulmonary
      resuscitation (CPR) was performed in 45% of cases. Initial rhythm was shockable
      in 26% of cases. A total of 1,332 patients (35%) were admitted alive to hospital.
      Among hospitalized patients, 58% had a coronary angiogram, and the same
      proportion had therapeutic hypothermia. Finally, 279 patients (7.5%) were
      discharged alive, of whom 96% had a favorable neurological outcome. In
      multivariate analysis, bystander CPR (OR 2.1, 95% CI 1.5-3.1) and initial
      shockable rhythm (OR 11.5, 95% CI 7.6-17.3) were positively associated with
      survival at hospital discharge, whereas age (OR 0.97 per year, 95% CI 0.96-0.98),
      longer response time (OR 0.93 per minute, 95% CI 0.89-0.97), occurrence at home
      (OR 0.4, 95% CI 0.3-0.6), and epinephrine dose greater than 3 mg (OR 0.05, 95% CI
      0.03-0.08) were inversely associated with survival. CONCLUSION: Despite being
      conducted in the therapeutic hypothermia and early coronary angiogram era,
      hospital discharge survival rate of resuscitated SCD remains poor. The current
      registry suggests ways to improve pre-hospital and in-hospital care of these
      patients.

PMID- 24658914
TI  - The intensive care management of acute   ischemic stroke: an overview.
AB  - PURPOSE: Acute ischemic stroke (AIS) is a leading cause of morbidity and
      mortality worldwide. In part due to the availability of more aggressive
      treatments, increasing numbers of patients with AIS are being admitted to the
      intensive care unit (ICU). Despite the availability of consensus guidance for the
      general management of AIS, there is little evidence to support its ICU
      management. The purpose of this article is to provide a contemporary perspective,
      and our recommendations, on the ICU management of AIS. METHODS: We reviewed the
      current general AIS guidelines provided by the European Stroke Organisation, the
      American Stroke Association, and the U.K. National Institute for Health and Care
      Excellence, as well as the wider literature, for the data most relevant to the
      ICU management of AIS. RESULTS: There are four interventions in AIS supported by
      class I evidence: care on a stroke unit, intravenous tissue plasminogen activator
      within 4.5 h of stroke onset, aspirin within 48 h of stroke onset, and
      decompressive craniectomy for supratentorial malignant hemispheric cerebral
      infarction. However, robust evidence for specific AIS management principles in
      the ICU setting is weak. Management principles currently focus on airway and
      ventilation management, hemodynamic and fluid optimization, fever and glycemic
      control, management of anticoagulation, antiplatelet and thromboprophylaxis
      therapy, control of seizures and surgical interventions for malignant middle
      cerebral artery and cerebellar infarctions. CONCLUSIONS: We have provided our
      recommendations for the principles of ICU management of AIS, based on the best
      available current evidence. Encouragement of large-scale recruitment of patients
      with AIS into clinical trials should aid the development of robust evidence for
      the benefit of different interventions in the ICU on outcome.

PMID- 24658916
TI  - Long-term response to imatinib is not affected by the initial dose  in patients
      with Philadelphia chromosome-positive chronic  myeloid leukemia in chronic phase:
      final update from the Tyrosine  Kinase Inhibitor Optimization and Selectivity
      (TOPS) study.
AB  - The TOPS trial evaluated high- (800 mg/day; n = 319) versus standard-dose (400
      mg/day; n = 157) imatinib in patients newly diagnosed with Philadelphia
      chromosome-positive chronic myeloid leukemia in chronic phase. Patients had a
      minimum follow-up of 42 months or discontinued early. Major molecular response
      (MMR) rates were similar between arms at (51.6 vs 50.2 % for 400 and 800 mg/day,
      respectively; P = 0.77) and by (75.8 vs 79.0 %; P = 0.4807) 42 months. There were
      no differences in event-free survival (EFS), progression-free survival(PFS), or
      overall survival (OS) between arms. The estimated rates of PFS on treatment and
      OS at 42 months were significantly higher in patients with MMR at 6, 12, and 18
      months compared with those without MMR.Adverse events were more frequent with
      high-dose imatinib. Patients with B1 treatment interruption (vs [1) and those
      able to maintain imatinib C600 mg/day (vs?600 mg/day) in the first year of
      treatment had faster and higher response rates, but no improvement in EFS or PFS.
      Adherence to prescribed dose without interruption may be more important than
      initiation of therapy with higher doses of imatinib. Achievement of MMR
      correlated with longterm clinical outcomes.

PMID- 24658919
TI  - The effects of chronic exposure to environmentally relevant levels of waterborne
      cadmium on reproductive capacity and behaviour in fathead minnows.
AB  - Cadmium (Cd) is a priority pollutant in aquatic ecosystems because of its highly
      toxic effects at low concentrations. Recent work has highlighted that at
      sublethal concentrations, Cd can impair the ability of fish to respond to
      important sensory cues. In the present study, we examined whether chronic
      exposure to environmentally relevant concentrations of waterborne Cd (1, 2.5 and
      5 MUg/L) can result in reproductive impairment in fathead minnows (Pimephales
      promelas) as measured by the standard Organization for Economic Cooperation and
      Development (OECD) 21-day reproductive assay. In addition, we also evaluated the
      effects of chronic waterborne Cd exposure on Cd accumulation in target tissues
      (liver and ovary) and plasma estradiol level in females and on the reproductive
      behaviour of fathead minnows. We found that the standard endpoints used in the
      OECD reproductive assays (e.g., egg production, number of spawning attempts,
      brood size) are more sensitive to Cd exposure than behavioural endpoints;
      however, the traditional method of interpreting reproductive impairment may
      underestimate toxic effects. Cadmium accumulation in liver and ovary of fish
      increased with increasing Cd exposure concentrations; however, plasma estradiol
      level remained unaffected. Reproductive capacity in fathead minnows decreased at
      waterborne Cd concentrations as low as 1 MUg/L. The findings of our study have
      important implications for understanding the effects of chronic Cd exposure in
      metal-impacted feral fish populations.

PMID- 24658920
TI  - Toward ecologically realistic theories in visual short-term  memory research.
AB  - Recent evidence from neuroimaging and psychophysics suggests common neural and
      representational substrates for visual perception and visual short-term memory
      (VSTM).Visual perception is adapted to a rich set of statistical regularities
      present in the natural visual environment. Common neural and representational
      substrates for visual perception and VSTM suggest that VSTM is adapted to these
      same statistical regularities too. This article discusses how the study of VSTM
      can be extended to stimuli that are ecologically more realistic than those
      commonly used in standard VSTM experiments and what the implications of such an
      extension could be for our current view of VSTM. We advocate for the development
      of unified models of visual perception and VSTM-probabilistic and hierarchical in
      nature- incorporating prior knowledge of natural scene statistics.

PMID- 24658921
TI  - Multiple Gaussian network modes alignment reveals dynamically variable regions:
      the hemoglobin case.
AB  - Gaussian network model (GNM) modes of motion are calculated to a dataset of
      hemoglobin (Hb) structures and modes with dynamics similarity to the T state are
      multiply aligned. The sole criterion for the alignment is the mode shape itself
      and not sequence or structural similarity. Standard deviation (SD) of the GNM
      value score along the alignment is calculated, regions with high SD are defined
      as dynamically variable. The analysis shows that the alpha1beta1/alpha2beta2
      interface is a dynamically variable region but not the alpha1beta2/alpha2beta1
      and the alpha1alpha2/beta1beta2 interfaces. The results are in accordance with
      the T->R2 transition of Hb. We suggest that dynamically variable regions are
      regions that are likely to undergo structural change in the protein upon binding,
      conformational transition, or any other relevant chemical event. The represented
      technique of multiple dynamics-based alignment of modes is novel and may offer a
      new insight in proteins' dynamics to function relation.

PMID- 24658922
TI  - Characterization of secreted proteins of 2-cell mouse embryos  cultured in vitro
      to the blastocyst stage with and without protein  supplementation.
AB  - PURPOSE: To identify the secreted proteins of murine embryos grown in vitro.
      METHODS: Two-cell mouse embryos (n=432) were randomly allocated to culture to the
      blastocyst stage in protein-free and in protein-supplemented (3 % BSA) media.
      Proteins were separated by SDS-PAGE; bands were visualized by coomassie staining,
      followed by in-gel trypsin digestion and liquid chromatography-tandem mass
      spectrometry. RT-PCR and confocal microscopy were used to confirm gene/protein
      expression in blastocysts. RESULTS: Of all individually identified proteins, 34
      and 23 were found in embryos cultured without and with BSA, respectively, and 20
      were common. Identified proteins having an N-terminal secretory sequence or
      transmembrane domains located on the extracellular backbone were postulated as
      secreted proteins. Gene and protein expression for two selected molecules were
      confirmed. Functional analysis revealed over-represented processes related to
      lipid metabolism, cyclase activity, and cell adhesion/membrane functions.
      CONCLUSIONS: This study provided evidence to further characterize secreted
      proteins by mouse embryos grown from the 2-cell to the blastocyst stage in vitro.
      Because of homology between murine and human, these results may provide
      information to be translated to the clinical setting.

PMID- 24658923
TI  - Age-related increase in aneuploidy and alteration of gene expression in mouse
      first polar bodies.
AB  - PURPOSE: To confirm that aneuploidy candidate genes are detectable in the first
      polar body (PB(1)) of MII oocytes and to investigate the age-dependent molecular
      changes in PB(1). METHODS: Aged (12-to 15-mo-old) and young (2-mo-old) mice were
      administered pregnant mare's serum gonadotropin (PMSG) and human chorionic
      gonadotrophin (hCG). MII oocytes were obtained and the first PB was removed. mRNA
      from each PB and its sibling oocyte was reverse transcribed. Real-time PCR was
      performed to quantify the expression of six genes (BUB1, CDC20, Filia, MCAK,
      SGOL1, SMC1A) in single PB. RESULTS: We first demonstrated that detection and
      quantification of transcripts associated with aneuploidy in single mouse oocyte
      and sibling PB(1) is possible and the relative abundance of mRNA transcripts in a
      single PB faithfully reflects the relative abundance of that transcript in its
      sibling oocyte. We further found that transcript levels were significantly lower
      in aged PBs compared with young PBs (P<0.05). CONCLUSIONS: Our results suggest
      that the detection and analysis of polar body mRNA may provide insight in age
      related aneuploidy in oocyte. This analysis is a novel concept to investigate the
      genesis of chromosome abnormality and could potentially assist in the
      characterization of mechanisms underlying key molecular origin of female meiotic
      aneuploidy, which would be of great scientific and clinical value.

PMID- 24658924
TI  - Molecular and ultrastuctural changes of rat pre-implantation  embryos during two
      cell developmental arrest.
AB  - BACKGROUND: Rat pre-implantation embryos often suffer 2-cell stage developmental
      arrest and fail to progress further under in-vitro conditions. OBJECTIVE: In
      order to understand underlying mechanism leading to 2-cell arrest, we
      investigated the molecular changes, culture conditions and subcellular changes.
      METHODS: Gene expression in in-vivo developed 2-cell embryos (in-vivo), in- vitro
      developed 2-cell embryos (in-vitro), and in-vitro 2-cell arrested embryos
      (arrested) were investigated using microarrays and real-time PCR. Ultra
      structural changes were determined using electron microscopy. RESULTS: Gene
      expression was similar between in-vivo and in-vitro embryos. Over 2400 genes
      changed in arrested embryos compared to in-vivo and in-vitro embryos. The mRNAs
      encoding proteins involved in translation were elevated in arrested embryos. In
      vivo and in-vitro embryos highly expressed genes that were involved in cell
      cycle, and protein catabolic process compared to arrested embryos. Gene
      expression data suggested subcellular changes associated with 2-cell block.
      Transmission electron microscopy showed that in-vivo embryos had healthy
      subcellular structure, whereas arrested embryos did not have a nuclear membrane,
      contained small mitochondria and autophagic vacuoles. Furthermore, gene
      expression data was used for the optimization of culture media conditions to
      obtain better in-vitro embryonic development. Comparison of five and 20 % oxygen
      in culture resulted in two times more blastocyst formation with 5 % oxygen.
      CONCLUSIONS: These results showed that although all experimental groups appeared
      morphologically similar, arrested embryos had ultra-structural and molecular
      changes associated with oxidative stress and apoptosis. In-vitro culture under
      low oxygen and media additives reduced 2-cell block in rat embryos.

PMID- 24658925
TI  - Seminal superoxide dismutase activity and its relationship  with semen quality
      and SOD gene polymorphism.
AB  - PURPOSE: Superoxide dismutase (SOD) is an important component of antioxidative
      defense systems and plays an important role in protecting spermatozoa from
      oxidative damage. In this study, we assessed seminal SOD activity, its
      association with semen parameters, and also genetic and non-genetic factors
      contributing to the determination of SOD activity in infertile men. METHODS:
      Semen samples were obtained from 435 male infertility patients. Sperm DNA damage
      levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay.
      Four single nucleotide polymorphisms (SNPs) in SOD2 and SOD3 genes were genotyped
      using OpenArray platform. RESULTS: We found that seminal SOD activity was
      positively associated with sperm concentration and overall motility, whereas
      inversely with sperm DNA fragmentation. In addition, infertile men with SOD2
      rs4880 CC variants showed a low level of SOD activity when compared with TT
      carriers (Mean +/- SD: 268.3 +/- 102.3 and 342.8 +/- 98.2, respectively, P =
      0.005). Those who consumed vitamin C/E (>=3 times per week) had a significantly
      higher SOD activity level than those who did not (mean +/- SD: 379.8 +/- 93.3 and
      332.2 +/- 94.9, respectively, P = 0.001). CONCLUSIONS: Seminal SOD activity and
      other factors influencing SOD activity play a role in determining sperm
      fertilization potential and male infertility.

PMID- 24658926
TI  - The Asn680Ser polymorphism of the follicle stimulating hormone receptor gene and
      ovarian cancer risk: a meta-analysis.
AB  - PURPOSE: The purpose of this study was to conduct a meta-analysis to assess the
      association between FSHR Asn680Ser polymorphism and ovarian cancer
      susceptibility. METHODS: A literature search was conducted in PubMed, Embase and
      the China National Knowledge Infrastructure (CNKI) for all relevant studies
      published up to September 2013. The pooled odds ratios (ORs) with the
      corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate
      the association. RESULTS: Four case-control studies including 474 ovarian cancer
      cases and 659 controls met the inclusion criteria. The pooled analyses showed
      that FSHR Asn680Ser polymorphism was associated with the risk of ovarian cancer
      (Ser vs Asn: OR=1.295, 95 % CI 1.057-1.498, P=0.01; Ser/Ser + Asn/Ser vs Asn/Asn:
      OR=1.611, 95 % CI 1.027-2.528, P=0.038). Subgroup analyses by ethnicity
      (Caucasian and Asian) further revealed significant associations among Asians (Ser
      vs Asn: OR=1.386, 95 % CI 1.066-1.802, P=0.015; Ser/Ser + Asn/Ser vs Asn/Asn:
      OR=1.893, 95 % CI 1.329-2.689, P=0.000) but not Caucasians. There was no obvious
      risk of publication bias. CONCLUSIONS: The meta-analysis suggests that FSHR
      Asn680Ser polymorphism may be a risk factor for ovarian cancer in Asians. Due to
      the limited quantity of the included studies, further studies are needed to
      validate the above conclusions.

PMID- 24658927
TI  - Pyridoxine or pyridoxal-5'-phosphate for neonatal epilepsy: the distinction just
      got murkier.

PMID- 24658928
TI  - Placebo: from belief to movement.

PMID- 24658929
TI  - Stroke and nonstroke brain attacks in children.
AB  - OBJECTIVES: To determine symptoms, signs, and etiology of brain attacks in
      children presenting to the emergency department (ED) as a first step for
      developing a pediatric brain attack pathway. METHODS: Prospective observational
      study of children aged 1 month to 18 years with brain attacks (defined as
      apparently abrupt-onset focal brain dysfunction) and ongoing symptoms or signs on
      arrival to the ED. Exclusion criteria included epilepsy, hydrocephalus, head
      trauma, and isolated headache. Etiology was determined after review of clinical
      data, neuroimaging, and other investigations. A random-effects meta-analysis of
      similar adult studies was compared with the current study. RESULTS: There were
      287 children (46% male) with 301 presentations over 17 months. Thirty-five
      percent arrived by ambulance. Median symptom duration before arrival was 6 hours
      (interquartile range 2-28 hours). Median time from triage to medical assessment
      was 22 minutes (interquartile range 6-55 minutes). Common symptoms included
      headache (56%), vomiting (36%), focal weakness (35%), numbness (24%), visual
      disturbance (23%), seizures (21%), and altered consciousness (21%). Common signs
      included focal weakness (31%), numbness (13%), ataxia (10%), or speech
      disturbance (8%). Neuroimaging included CT imaging (30%), which was abnormal in
      27%, and MRI (31%), which was abnormal in 62%. The most common diagnoses included
      migraine (28%), seizures (15%), Bell palsy (10%), stroke (7%), and conversion
      disorders (6%). Relative proportions of conditions in children significantly
      differed from adults for stroke, migraine, seizures, and conversion disorders.
      CONCLUSIONS: Brain attack etiologies differ from adults, with stroke being the
      fourth most common diagnosis. These findings will inform development of ED
      clinical pathways for pediatric brain attacks.

PMID- 24658931
TI  - Increased optic nerve radiosensitivity following optic neuritis.

PMID- 24658930
TI  - Another face of placebo: the lessebo effect in Parkinson disease: meta-analyses.
AB  - OBJECTIVE: To study the impact of negative expectation related to receiving a
      placebo (the "lessebo effect") on efficacy outcome measures of symptomatic
      treatments in Parkinson disease (PD). METHODS: We conducted meta-analyses of
      double-blind randomized controlled trials (RCTs) of dopamine agonists in PD and
      compared the pooled mean score change of the motor section of the Unified
      Parkinson's Disease Rating Scale (mUPDRS) across active treatment arms according
      to the presence of a placebo arm or the probability of placebo assignment (0%,
      <50%, and 50%) of the original RCT. A mixed-effects model was used. Heterogeneity
      was assessed by subgroup analyses and meta-regression modeling. RESULTS: A total
      of 28 study arms were extracted from active-controlled trials (3,277 patients)
      and 42 from placebo-controlled trials (4,554 patients). The overall difference
      between groups in the pooled mean score change in the mUPDRS was 1.6 units (95%
      confidence interval [CI] 0.2, 3.0; p = 0.023), in favor of the active-controlled
      group. In subgroup analyses, this difference was of higher magnitude in the early
      PD group without motor fluctuations (3.3 mUPDRS units, 95% CI 1.1, 5.4; p =
      0.003) and for study duration <= 12 weeks (4.1 mUPDRS units, 95% CI 1.0, 7.2; p =
      0.009). There was no between-group difference using probability of placebo
      assignment as criterion. CONCLUSIONS: This study shows that the use of a placebo
      can be associated with a clinically significant reduction in the magnitude of
      change of the mUPDRS after an active treatment in RCTs for PD. These new findings
      have potential implications in the development of new treatments and appraisal of
      current treatment options for PD and possibly for other neurologic disorders.

PMID- 24658932
TI  - Migraine trait symptoms in migraine with and without aura.
AB  - OBJECTIVES: The aim of the study was to determine whether various transient
      sensory and neuropsychological symptoms (SNS) were associated with migraine using
      a custom questionnaire. METHODS: In this hypothesis-generating case-control
      study, the frequencies of transient SNS in 219 patients with migraine (149
      without aura and 70 with aura) were compared with 161 age- and sex-matched
      healthy controls using a custom questionnaire. Patients from a tertiary academic
      headache center in Hamburg were contacted by regular mail. Healthy controls
      without a history of migraine were recruited by means of a screening
      questionnaire and consecutively approached by e-mail. RESULTS: The presence of
      both migraine and aura was associated with significantly higher frequencies of
      autokinesis, metamorphopsia, dyschromatopsia, cinematographic vision, illusionary
      visual spread, and synesthesia (for all comparisons: corrected p < 0.05). Double
      vision, inverted 2- and 3-dimensional vision, and altered perception of body
      weight and size were found more often in patients with migraine without aura than
      in those with aura. In contrast, aura was associated with the occurrence of
      visual splitting and corona phenomenon (for all comparisons: corrected p < 0.05).
      No relevant association with migraine was found for micropsia and macropsia,
      teleopsia and pelopsia, inverted vision, out-of-body experience, Doppelganger
      phenomenon, complex visual hallucinations, and altered perception of body
      position in space. CONCLUSIONS: The observed SNS seem to belong to a physiologic
      spectrum of multisensory phenomena. Some of these phenomena were significantly
      accentuated in patients with migraine and may therefore be termed migraine trait
      symptoms. However, these results will have to be confirmed in a prospective study
      with face-to-face interviews.

PMID- 24658934
TI  - Adaptive functioning of childhood brain tumor survivors following conformal
      radiation therapy.
AB  - Adaptive functioning is not often examined in childhood brain tumor (BT)
      survivors, with the few existing investigations relying on examiner interviews.
      Parent questionnaires may provide similar information with decreased burden. The
      purpose of this study was: (1) to examine adaptive behaviors in BT survivors
      relative to healthy peer and cancer survivor groups, and (2) to explore the
      validity of a parent questionnaire in relation to an examiner administered
      interview. Participants (age 13.11 +/- 2.98 years) were BT survivors treated with
      conformal radiation therapy (n = 50), healthy siblings of BT survivors (n = 39)
      and solid tumor (ST) survivors who did not receive CNS-directed therapy (n = 40).
      Parents completed the Adaptive Behavior Assessment System-2nd Edition (ABAS-II).
      For a subset of the BT cohort (n = 32), examiners interviewed the parents using
      the Vineland Adaptive Behavior Scales (VABS) within 12 months. Groups differed
      significantly on each of the ABAS-II indices and the general adaptive composite,
      with the BT group scoring lower than the sibling and ST groups across indices.
      Executive functioning, but not IQ, was associated with adaptive skills; no clear
      pattern of clinical and demographic predictors was established. VABS scores were
      correlated with ABAS-II scores on nearly all indices. BT survivors showed
      significantly lower adaptive functioning when compared to healthy and cancer
      controls. The ABAS-II proved sensitive to these behavioral limitations and was
      consistent with scores on the VABS. The use of a parent questionnaire to assess
      adaptive functioning enhances survivorship investigations by increasing
      flexibility of assessment and decreasing examiner burden.

PMID- 24658935
TI  - Role of sonography and magnetic resonance imaging in detecting deltoideal
      acromial enthesopathy: an early finding in the diagnosis of spondyloarthritis and
      an under-recognized cause of posterior shoulder pain.
AB  - The acromial origin of the deltoid is a target structure of ankylosing
      spondylitis and related spondyloarthritis, which are often overlooked and
      underdiagnosed as causes of posterior shoulder pain. The objective of this
      article is to review the roles of sonography and magnetic resonance imaging in
      detecting deltoideal acromial enthesopathy and their importance for optimizing
      management in individuals with posterior shoulder pain. Adequate awareness of
      such enthesopathy as a potential manifestation of inflammatory rheumatic
      disorders is critical for early diagnosis of spondyloarthritis. 

PMID- 24658933
TI  - Pyridoxine responsiveness in novel mutations of the PNPO gene.
AB  - OBJECTIVE: To determine whether patients with pyridoxine-responsive seizures but
      normal biomarkers for antiquitin deficiency and normal sequencing of the ALDH7A1
      gene may have PNPO mutations. METHODS: We sequenced the PNPO gene in 31 patients
      who fulfilled the above-mentioned criteria. RESULTS: We were able to identify 11
      patients carrying 3 novel mutations of the PNPO gene. In 6 families, a homozygous
      missense mutation p.Arg225His in exon 7 was identified, while 1 family was
      compound heterozygous for a novel missense mutation p.Arg141Cys in exon 5 and a
      deletion c.279_290del in exon 3. Pathogenicity of the respective mutations was
      proven by absence in 100 control alleles and expression studies in CHO-K1 cell
      lines. The response to pyridoxine was prompt in 4, delayed in 2, on EEG only in
      2, and initially absent in another 2 patients. Two unrelated patients homozygous
      for the p.Arg225His mutation experienced status epilepticus when switched to
      pyridoxal 5'-phosphate (PLP). CONCLUSIONS: This study challenges the paradigm of
      exclusive PLP responsiveness in patients with pyridoxal 5'-phosphate oxidase
      deficiency and underlines the importance of consecutive testing of pyridoxine and
      PLP in neonates with antiepileptic drug-resistant seizures. Patients with
      pyridoxine response but normal biomarkers for antiquitin deficiency should
      undergo PNPO mutation analysis.

PMID- 24658936
TI  - Nodular fasciitis: characteristic imaging features on sonography and magnetic
      resonance imaging.
AB  - OBJECTIVES: The purpose of this study was to evaluate the imaging features of
      nodular fasciitis on sonography and magnetic resonance imaging (MRI). METHODS: A
      retrospective search of the radiologic and pathologic databases over the past 10
      years for the diagnosis of nodular fasciitis was performed. Sonographic and MRI
      features were described. Pathologic specimens were reviewed. RESULTS: Six
      pathologically confirmed cases of nodular fasciitis were found. The mean patient
      age was 19.5 years (range, 8-33 years); 3 patients were male and 3 were female.
      Four patients had sonography only; 1 patient had both sonography and MRI; and 1
      patient had MRI only. Three masses were located in the subcutaneous tissue
      adjacent to fascia; 2 were at the subcutaneous/muscular border; and 1 was
      intramuscular; however, all were in contact with fascia and showed a fascial tail
      on sonography and MRI. On sonography and MRI, masses were oval with poorly
      defined lobulated borders, averaging 2.6 cm (range, 1.8-3.5 cm). On sonography,
      all masses were hypoechoic. On MRI, the masses were isointense to muscle on T1
      weighted sequences, hyperintense to muscle on fluid-sensitive sequences, and
      enhanced avidly but heterogeneously. The masses were surrounded by fat.
      CONCLUSIONS: When a rapidly growing oval mass in contiguity with a fascial plane
      is recognized, the diagnosis of nodular fasciitis should be entertained. More
      importantly, the possibility of an inaccurate diagnosis by core biopsy exists,
      which may warrant gross resection.

PMID- 24658937
TI  - Double-contrast-enhanced sonography for diagnosis of rectal lesions with
      pathologic correlation.
AB  - OBJECTIVES: Transabdominal sonography with a gastrointestinal contrast agent has
      been widely used in China for investigation of digestive disorders. Double
      contrast-enhanced sonography combines a gastrointestinal luminal contrast agent
      with an intravenous contrast agent for imaging of lesions. The purpose of this
      pilot study was to assess the value of double-contrast-enhanced sonography for
      preoperative diagnosis of rectal lesions. METHODS: We conducted a prospective
      single-center study using double-contrast-enhanced sonography of rectal lesions.
      Patients were administered both rectal and intravenous contrast agents, and
      imaging was performed transabdominally, transanally, and transrectally.
      Morphologic characteristics and perfusion parameters were compared between
      histologically proven adenocarcinomas, adenomas, and inflammatory masses.
      Perfusion parameters were analyzed with time-intensity curves, measuring the
      contrast arrival time, time to peak, peak intensity, and area under the curve of
      the lesions and normal rectal tissue. RESULTS: From January 2009 to September
      2012, 420 patients were recruited, with 227 patients meeting inclusion/exclusion
      criteria and having 232 rectal lesions analyzed (172 rectal adenocarcinomas, 45
      adenomas, and 15 inflammatory masses). Adenocarcinomas had variable enhancement
      patterns. Adenomas were all hypoenhanced in a homogeneous pattern. Inflammatory
      masses had a hyperenhanced rim with no central enhancement. Time-intensity curve
      perfusion parameters (arrival time, time to peak, peak intensity, and area under
      the curve) of rectal adenocarcinomas, adenomas, and inflammatory masses were
      significantly different compared to normal rectal tissue (P < .05). The
      differences in the arrival time, peak intensity, and time to peak among the
      different lesions were also significant (P < .05). CONCLUSIONS: Double-contrast
      enhanced sonographic assessment of morphologic enhancement patterns combined with
      vascularity parameters may help differentiate benign and malignant rectal
      lesions.

PMID- 24658938
TI  - Virtual touch tissue imaging on acoustic radiation force impulse elastography: a
      new technique for differential diagnosis between benign and malignant thyroid
      nodules.
AB  - Objectives- Acoustic radiation force impulse elastography is a newly developed
      ultrasound elasticity imaging technique that included both Virtual Touch tissue
      quantification and Virtual Touch tissue imaging (VTI; Siemens Medical Solutions,
      Mountain View, CA). This study aimed to evaluate the usefulness of VTI in
      differentiating malignant from benign thyroid nodules. Methods- This study
      included 192 consecutive patients with thyroid nodules (n = 219) who underwent
      surgery for compressive symptoms or suspicion of malignancy. Tissue stiffness on
      VTI elastography was scored from 1 (soft) to 6 (hard). The VTI scores between
      malignant and benign thyroid nodules were compared. The intraobserver and
      interobserver agreement for VTI elastography was also assessed. Results- On VTI
      elastography: score 1 was found in 84 nodules (all benign); score 2 in 37 nodules
      (3 papillary carcinomas and 34 benign nodules); score 3 in 25 nodules (1
      medullary carcinoma, 6 papillary carcinomas, and 18 benign nodules); score 4 in
      53 nodules (50 papillary carcinomas and 3 benign nodules); score 5 in 17 nodules
      (14 papillary carcinomas and 3 benign nodules); and score 6 in 3 nodules (all
      papillary carcinomas). A VTI elasticity score of 4 or greater was highly
      predictive of malignancy (P< .01), and the sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy were 87.0% (67 of 77),
      95.8% (136 of 142), 91.8% (67 of 73), 93.1% (136 of 146), and 92.7% (203 of 219),
      respectively. The kappa values were 0.69 for intraobserver agreement and 0.85 for
      interobserver agreement. Conclusions- Virtual Touch tissue elasticity imaging has
      great potential as an adjunctive tool combined with conventional sonography for
      differential diagnosis between benign and malignant thyroid nodules. 

PMID- 24658939
TI  - A novel approach for quantification and analysis of the color Doppler twinkling
      artifact with application in noninvasive surface roughness characterization: an
      in vitro phantom study.
AB  - OBJECTIVES: The twinkling artifact is an undesired phenomenon within color
      Doppler sonograms that usually appears at the site of internal calcifications.
      Since the appearance of the twinkling artifact is correlated with the roughness
      of the calculi, noninvasive roughness estimation of the internal stones may be
      considered as a potential twinkling artifact application. This article proposes a
      novel quantitative approach for measurement and analysis of twinkling artifact
      data for roughness estimation. METHODS: A phantom was developed with 7 quantified
      levels of roughness. The Doppler system was initially calibrated by the proposed
      procedure to facilitate the analysis. A total of 1050 twinkling artifact images
      were acquired from the phantom, and 32 novel numerical measures were introduced
      and computed for each image. The measures were then ranked on the basis of
      roughness quantification ability using different methods. The performance of the
      proposed twinkling artifact-based surface roughness quantification method was
      finally investigated for different combinations of features and classifiers.
      RESULTS: Eleven features were shown to be the most efficient numerical twinkling
      artifact measures in roughness characterization. The linear classifier
      outperformed other methods for twinkling artifact classification. The pixel count
      measures produced better results among the other categories. The sequential
      selection method showed higher accuracy than other individual rankings. The best
      roughness recognition average accuracy of 98.33% was obtained by the first 5
      principle components and the linear classifier. CONCLUSIONS: The proposed
      twinkling artifact analysis method could recognize the phantom surface roughness
      with average accuracy of 98.33%. This method may also be applicable for
      noninvasive calculi characterization in treatment management.

PMID- 24658940
TI  - Contrast-enhanced sonographically guided percutaneous 915-MHz microwave ablation
      therapy compared to local hemostatic drug injection in a renal artery injury
      model.
AB  - OBJECTIVES: The purpose of this study was to show the contrast-enhanced
      sonographic features of various levels of renal artery rupture and to validate
      the therapeutic effects of percutaneous 915-MHz microwave ablation compared to
      hemostatic drug injection (batroxobin) using an in vivo canine renal artery
      injury model. METHODS: Three renal artery hemorrhage models (A, diameter <1 mm,
      subcapsular artery; B, diameter 1-2 mm, interlobar artery; and C, diameter 2-3
      mm, segmental artery) were created in 24 canines for this study. Contrast
      enhanced sonography was used to show the bleeding features and guide hemostatic
      therapies using 915-MHz microwave ablation and local batroxobin injection.
      Success rates were assessed according to amounts of bleeding, times required for
      hemostatic action, and volumes of fluid infusion required using pathologic
      examination as a reference standard. RESULTS: Contrast-enhanced sonography
      clearly showed renal artery ruptures with active bleeding at various levels and
      degrees and was very useful to make diagnoses and guide therapies. The success
      rate in the microwave treatment group was higher than that in the drug injection
      group (except group A; P< .05). The time required for hemostasis and the volume
      of fluid infusion required in the microwave group were notably less than those in
      the drug injection group (P < .05). CONCLUSIONS: Contrast-enhanced sonography is
      a useful imaging method for assessing renal vessel injury and guide
      interventional therapies. Contrast-enhanced sonographically guided percutaneous
      915-MHz microwave ablation is a preferred hemostatic technique for treatment of
      renal artery injury, with greater effectiveness and less tissue damage compared
      to local drug injection.

PMID- 24658941
TI  - Do echo-enhanced needles make a difference in sonographically guided vascular
      access?
AB  - OBJECTIVES: The purpose of this study was to compare sonographically guided
      vascular access using standard and echo-enhanced needles in a variety of tissue
      simulating vascular phantoms. METHODS: We conducted a prospective single-blinded
      observational study at an academic medical center. All participants performed
      real-time sonographically guided vascular access using both a standard 18-gauge
      needle and an echo-enhanced needle in both in-plane and out-of plane approaches
      on 3 different vascular access phantoms. The outcome measures included time to
      dye flash, first-pass success, visibility of the needle tip at the time of
      puncture, total number of attempts, number of redirections, and incidence of
      posterior wall penetration. RESULTS: A total of 408 sonographically guided
      cannulations were performed by 34 participants. The time from needle stick to dye
      flash, first-pass success, and the total number of attempts were not
      significantly different between the two needles (P> .05). The tip of the needle
      was seen at the time of puncture in 79% of attempts with the standard needle (95%
      confidence interval [CI], 68%-86%) and in 86% of attempts with the echo-enhanced
      needle (95% CI, 76%-92%), although this difference was not significant (P= .103).
      The posterior wall was penetrated with the standard needle in 14% of attempts
      (95% CI, 9.6%-20%) and in 6% of attempts with the echo-enhanced needle (95% CI,
      3.5%-11%), and the difference was significant (P < .02). CONCLUSIONS: Echo
      enhanced needles decreased the incidence of posterior wall punctures when
      compared to standard needles during sonographically guided vascular access.
      However, there were no significant differences in other sonographically guided
      vascular access metrics.

PMID- 24658942
TI  - Effect of carotid artery stenting on ophthalmic artery flow patterns.
AB  - OBJECTIVES: The purpose of this study was to assess the effect of carotid artery
      stenting on ophthalmic artery blood flow using transorbital color and spectral
      Doppler sonography and review the changes in relation to cerebral hemodynamics.
      METHODS: Twenty-eight consecutive patients with severe internal carotid artery
      stenosis (>= 70%) who were scheduled for carotid stenting were included.
      Ophthalmic artery Doppler sonography was performed bilaterally before and after
      stenting. The flow direction, peak systolic velocity (PSV), end-diastolic
      velocity (EDV), pulsatility index (PI), and resistive index in the ophthalmic
      artery were recorded. RESULTS: Twenty male and 8 female patients with 10 right
      sided and 18 left-sided stenoses were studied. The mean overall carotid stenosis
      ratio +/- SD was 87.3% +/- 9.9%. After stenting in the ophthalmic artery
      ipsilateral to the stenosis, significant increases in the PSV (-3.87 +/- 48.81 to
      46.70 +/- 25.33 cm/s; P < .001), and EDV (-3.02 +/- 16.31 to 11.24 +/- 7.37 cm/s;
      P < .001) were detected, and the increase in the PI approached significance (1.40
      +/- 0.59 to 1.62 +/- 0.52; P = .055). A change in the flow direction from
      retrograde to antegrade was noted in 11 patients (39%) after stenting, and in 1
      patient with no detectable flow, reconstitution of flow was observed. Increases
      in the PSV and EDV (P= .03 for DeltaEDV) were more pronounced in symptomatic
      patients than asymptomatic patients after stenting. CONCLUSIONS: Substantially
      decreased ophthalmic artery velocity and retrograde flow are suggestive of high
      grade carotid artery stenosis (?90%). Stenting improves ophthalmic artery
      perfusion and positively changes cerebral hemodynamics in high-grade carotid
      artery stenosis, especially in symptomatic patients, which can be monitored with
      ophthalmic artery Doppler sonography.

PMID- 24658943
TI  - Bayesian probability of malignancy with BI-RADS sonographic features.
AB  - OBJECTIVES: The purpose of this study was to develop a quantitative approach for
      combining individual American College of Radiology Breast Imaging Reporting and
      Data System (BI-RADS) sonographic features of breast masses for assessing the
      overall probability of malignancy. METHODS: Sonograms of solid breast masses were
      analyzed by 2 observers blinded to patient age, mammographic features, and lesion
      pathologic findings. BI-RADS sonographic features were determined by using
      American College of Radiology criteria. A naive Bayes model was used to determine
      the probability of malignancy of all the sonographic features together and with
      age and BI-RADS mammographic features. The diagnostic performance for various
      combinations was evaluated by using the area under the receiver operating curve
      (Az). RESULTS: Sonographic features had high positive and negative predictive
      values. The Az values for BI-RADS sonographic features for the 2 observers ranged
      from 0.772 to 0.884, which increased to 0.866 to 0.924 when used with patient age
      and BI-RADS mammographic features. The benefit of adding age and mammographic
      information was more marked for the observer with lower initial diagnostic
      performance. Age-specific analysis showed that diagnostic performance varied with
      age, with higher performance for patients aged 45 years and younger and patients
      older than 60 years compared to those aged 46 to 60 years. In 85% of cases, the
      diagnosis of the observers matched. When the consensus between the observers was
      used for diagnostic decisions, a high level of diagnostic performance (Az, 0.954)
      was achieved. CONCLUSIONS: A naive Bayes model provides a systematic approach for
      combining sonographic features and other patient characteristics for assessing
      the probability of malignancy to differentiate malignant and benign breast
      masses.

PMID- 24658944
TI  - Learning curves in 3-dimensional sonographic follicle monitoring during
      controlled ovarian stimulation.
AB  - OBJECTIVES: Three-dimensional (3D) sonographically based automated volume
      calculation (SonoAVC; GE Healthcare, Zipf, Austria) is being introduced in
      folliculometry during ovarian stimulation; however, clear training assessments in
      this technique are lacking. The learning curve-cumulative summation (LC-CUSUM)
      test provides a quantitative tool to determine when a trainee has learned a
      procedure. The aim of this prospective study was to assess 3D SonoAVC LC-CUSUM
      curves in folliculometry. METHODS: Analyses were performed on 98 oocyte donors by
      capturing the ovarian image in 3D and applying the 3D SonoAVC software during
      ovarian stimulation cycles. Each patient was scanned by an expert operator and by
      a trainee. Independent LC-CUSUM tests for 4 follicular diameters tracked the
      competency of 3 trainees in 3D SonoAVC. RESULTS: We found that the numbers of
      sonographic examinations required by the 3 trainees to identify the correct
      number of follicles of 10 mm or larger were 38, 32, and 28, respectively; for
      follicles of 14 mm or larger, they were 29, 28, and 28; for follicles of 18 mm or
      larger, they were 24, 19, and 27; and for follicles of 21 mm or larger, they were
      29, 19, and 24. CONCLUSIONS: A variable number of procedures are needed to reach
      proficiency in 3D SonoAVC, even for trained 2-dimensional sonographers.
      Assessment of learning curves should be implemented when incorporating 3D SonoAVC
      in reproduction units.

PMID- 24658945
TI  - A case-control study of high-intensity focused ultrasound combined with
      sonographically guided intratumoral ethanol injection in the treatment of uterine
      fibroids.
AB  - OBJECTIVES: The purpose of this study was to explore the feasibility of high
      intensity focused ultrasound combined with sonographically guided intratumoral
      ethanol injection in the treatment of uterine fibroids and to compare its
      therapeutic effects and potential side effects with those of simple high
      intensity focused ultrasound treatment. METHODS: Forty patients with uterine
      fibroids from the Department of Ultrasonography in our hospital were randomly
      divided into 2 groups of the same size: group H, which only underwent high
      intensity focused ultrasound treatment; and group H + A, which underwent
      sonographically guided intratumoral ethanol injection therapy first and then high
      intensity focused ultrasound treatment the following day. The treatment times,
      treatment doses, pain scores, side effects, and therapeutic effect rates of the
      groups were then recorded and compared. RESULTS: Both the treatment time and dose
      of group H + A were significantly less than those of group H, and the differences
      were statistically significant (P < .05). A lower pain score and fewer side
      effects were achieved in group H + A, also with statistically significant
      differences (P < .05). The therapeutic effect rate of group H + A was also higher
      than that of group H, and the difference was also statistically significant (P <
      .05). CONCLUSIONS: In the treatment of uterine fibroids, high-intensity focused
      ultrasound combined with sonographically guided intratumoral ethanol injection
      requires less treatment time and a lower dose than simple high-intensity focused
      ultrasound treatment and significantly reduces the pain and side effects commonly
      experienced by patients. High-intensity focused ultrasound combined with
      sonographically guided intratumoral ethanol injection is a feasible, safe, and
      more effective way to treat patients with uterine fibroids.

PMID- 24658946
TI  - Ultrasound elastography in the differential diagnosis of benign and malignant
      cervical lesions.
AB  - OBJECTIVES: This study aimed to evaluate the clinical value of ultrasound
      elastography in the differential diagnosis of benign and malignant cervical
      lesions and to compare the accuracy of the elasticity score and strain ratio in
      differentiating cervical lesions. METHODS: B-mode sonography and ultrasound
      elastography were performed on 84 cervical lesions (40 benign and 44 malignant)
      in 84 patients. All of the images were obtained transvaginally. The elasticity
      score was determined by a 5-point scoring method. Calculation of the strain ratio
      was based on a comparison of the average strain measured in the lesion with the
      adjacent tissue of the same depth, size, and shape. The findings were compared
      with histopathologic results. With the use of receiver operating characteristic
      curves, the diagnostic value of the elasticity score and strain ratio methods was
      determined. RESULTS: The sensitivity, specificity, accuracy, positive predictive
      value, and negative predictive value of the elasticity score in the differential
      diagnosis of cervical lesions were 81.8%, 85.0%, 83.3%, 85.7%, and 81.0%,
      respectively, whereas those of the strain ratio were 90.9%, 90.0%, 90.5%, 90.9%,
      and 90.0%. A strain ratio cutoff value of 4.525 was used as a standard to
      distinguish benign from malignant lesions. The strain ratio values of malignant
      lesions were much higher than those of benign lesions (range, 4.85-8.91 versus
      0.62-4.50). The differences were statistically significant (P < .01).
      CONCLUSIONS: Ultrasound elastography is a promising technique that is easy and
      rapid to perform and can help identify cervical lesions that are likely to be
      malignant. It is obvious that the strain ratio yielded better results than the
      elasticity score. Both methods are semiquantitative, but quantification of the
      strain ratio is finer than that of the elasticity score.

PMID- 24658947
TI  - Role of 3-dimensional power Doppler sonography in differentiating pregnant women
      with threatened preterm labor from those with an asymptomatic short cervix.
AB  - OBJECTIVES: To compare cervical volumes and vascularization indices using 3
      dimensional power Doppler sonography among singleton pregnancies with threatened
      preterm labor and an asymptomatic short cervix. METHODS: Three hundred
      asymptomatic healthy pregnant women between 24 and 34.6 gestational weeks were
      prospectively scanned for cervical length. If cervical length was short, defined
      as below the 10th percentile for gestational age, the cervical volume and
      vascularization indices (vascularization index [VI], vascularization-flow index
      [VFI], and flow index [FI]) were measured. Women receiving any treatment for
      preterm delivery prevention were excluded. During this period, the same
      sonographic parameters were measured among patients with threatened preterm labor
      admitted to our institution during the first 24 hours after admission. Multiple
      pregnancies and fetal or maternal pathologic conditions, were exclusion criteria.
      Data on body mass index, maternal age, smoking, parity, family history of preterm
      birth, mother who was born preterm, and previous preterm birth among the pregnant
      women were recorded. Sonographic and medical history parameters were compared
      between the two groups. RESULTS: Twenty-nine asymptomatic healthy women (9.6%)
      had a short cervix. Additionally, 71 pregnancies with threatened preterm labor
      were scanned. There were no statistically significant differences between the
      groups in medical history parameters or cervical length. The cervical volume was
      smaller in threatened preterm cases (12.90 versus 17.168 cm(3); P = .005). The VI
      and VFI were lower in women with an asymptomatic short cervix (VI, 4.369% versus
      15.939%; P < .001; VFI, 1.514 versus 4.878; P < .001). The FI was higher in the
      short cervix group (33.581 versus 30.311; P = .006). CONCLUSIONS: Three
      dimensional transvaginal sonography reveals differences in cervical volume and
      vascularization indices between pregnancies with an asymptomatic short cervix and
      cases with threatened preterm labor, although cervical length is similar in both
      groups.

PMID- 24658948
TI  - Feasibility of detection of the 3-vessel and trachea view using 3-dimensional
      sonographic volumes.
AB  - OBJECTIVES: The purpose of this study was to investigate the ability to depict
      the 4-chamber and 3-vessel and trachea views of the fetal heart using 3
      dimensional sonography. METHODS: Three-dimensional color Doppler volumes of the
      fetal heart were acquired prospectively in 31 fetuses between 19 and 25
      gestational weeks. The initial plane consisted of the 4-chamber view.
      Postprocessing included navigation within the volume solely in plane A in the
      caudal direction to visualize the stomach and in the cephalic direction to the
      plane of the 3-vessel and trachea view to visualize the pulmonary artery, the
      aorta, the V shape and color of the arches, the superior vena cava, and the
      trachea. The feasibility of showing these organs was evaluated. RESULTS: The
      estimated time for volume acquisition and manipulation was about 60 seconds. The
      detection rates for the 4-chamber view, stomach, 3-vessel view, trachea, and V
      sign were 100%, 93.5%, 92.0%, 77.4%, and 83.9%, respectively, with interobserver
      agreement of 0.76 to 1.0. CONCLUSIONS: We describe a simple technique in which a
      single sweep on 3-dimensional sonography starting at the level of the 4-chamber
      view can visualize the situs, stomach, 4-chamber view, and transverse view of the
      outflow tracts of the heart.

PMID- 24658949
TI  - Impact of gestational age on nuchal fold thickness in the second trimester.
AB  - OBJECTIVES: The purpose of this study was to establish gestational age (GA)
      specific nomograms for nuchal fold thickness between 16 and 24 weeks. METHODS:
      This retrospective cross sectional study included 32,207 women who underwent a
      second-trimester anomaly scan at the Fetal Care Center of National University
      Hospital from January 2005 to April 2011. Nomograms were plotted for nuchal fold
      thickness at each gestation to study its variation with GA. RESULTS: Nuchal fold
      thickness increased with GA in a linear manner from 3.13 +/- 0.68 mm (mean +/-
      SD) at 16 weeks to 5.08 +/- 0.76 mm at 24 weeks. The 95th percentile measurement
      at 24 weeks remained less than 6 mm. CONCLUSIONS: A threshold of 6 mm appears to
      be appropriate for the diagnosis of a thick nuchal fold even for gestations
      between 20 and 24 weeks.

PMID- 24658950
TI  - Outcomes of pregnancies with a low-lying placenta diagnosed on second-trimester
      sonography.
AB  - OBJECTIVES: The purpose of this study was to determine how often a low-lying
      placenta, defined as a placenta ending within 2 cm of the internal cervical os
      but not covering it, diagnosed sonographically in the second trimester resolves
      before delivery. METHODS: After Institutional Review Board approval was obtained,
      1416 pregnancies with a sonographically diagnosed low-lying placenta between 16
      and 24 weeks' gestation were identified from our ultrasound database over a 5
      year period. We reviewed medical records to determine the gestational age at
      which the low-lying placenta was first diagnosed, the gestational age at which
      the placenta was no longer sonographically low lying or covering the cervix, and,
      of those whose placentas that never cleared the internal cervical os
      sonographically, how many went on to cesarean delivery as a result of placental
      location. RESULTS: In total, 1220 of 1240 low-lying placentas (98.4%) that had
      sonographic follow up resolved to no previa before delivery; 89.9% of placentas
      cleared the cervix by 32 weeks, and 95.9% cleared by 36 weeks. Twenty patients
      (1.6%) had persistent sonographic placenta previa or a low-lying placenta at or
      near term, including 5 complete previas, 7 marginal previas, 5 low-lying
      placentas, and 3 vasa previas; all had cesarean deliveries. CONCLUSIONS: A low
      lying placenta sonographically diagnosed in the second trimester typically
      resolves by the mid third trimester. Only rarely (1.6% of the time) does it
      persist to term or near term. Follow-up sonography is warranted to diagnose
      persistent placenta previa or vasa previa, a complication of a low-lying
      placenta.

PMID- 24658951
TI  - Adnexal sonographic findings in ectopic pregnancy and their correlation with
      tubal rupture and human chorionic gonadotropin levels.
AB  - OBJECTIVES: To determine whether the distribution of transvaginal sonographic
      findings of ectopic pregnancy has changed since the studies done 20 years ago and
      to explore the correlation of tubal rupture with transvaginal sonographic
      findings and human chorionic gonadotropin (hCG) levels. METHODS: Patients with
      ectopic pregnancy who underwent transvaginal sonography before treatment were
      included. Sonograms and medical records were retrospectively reviewed. The
      presence of a tubal ring, the presence of a yolk sac, embryonic cardiac activity,
      the degree of vascularity on color Doppler imaging, hCG levels, and results of
      surgery were recorded. RESULTS: Our study included 231 ectopic pregnancies. A
      positive sonographic adnexal finding was present in 219 cases (94.8%): adnexal
      mass in 218 (94.4%) and a moderate-to-large amount of free fluid in 84 (36.4%).
      The adnexal masses were graded as follows: 1, nonspecific mass (125 cases [54.1%
      of total]); 2, tubal ring without a yolk sac or embryo (57 [24.7%]); 3, yolk sac
      but no embryonic heartbeat (19 [8.3%]); and 4, embryo with cardiac activity (17
      [7.4%]). The mean hCG level increased as the grade ascended from 1 to 4. Thirty
      six patients had tubal rupture at surgery within 24 hours of the sonogram. A
      moderate-to-large amount of free fluid was significantly associated with tubal
      rupture (P < .05) but had low sensitivity, specificity, and positive predictive
      value for rupture. Other sonographic findings and hCG levels were not
      significantly related to tubal rupture. CONCLUSIONS: Transvaginal sonography
      showed an adnexal abnormality in nearly 95% of our patients with ectopic
      pregnancy, most commonly a nonspecific adnexal mass. Embryonic cardiac activity
      was seen in fewer than 10%. Neither sonographic findings nor hCG levels were
      useful predictors of tubal rupture.

PMID- 24658952
TI  - Borderline amniotic fluid index and its relation to fetal intolerance of labor: a
      2-center retrospective cohort study.
AB  - OBJECTIVES: To determine whether a borderline amniotic fluid index (AFI) in the
      third trimester is associated with an increased rate of cesarean delivery for
      fetal intolerance of labor, meconium-stained amniotic fluid, and intrauterine
      growth restriction, among other adverse perinatal outcomes. METHODS: Patients
      with a diagnosis of a borderline AFI between January 2008 and August 2012 were
      identified. Antepartum, delivery, and neonatal data were collected and compared
      to a cohort with a normal AFI. RESULTS: We enrolled 739 patients, including 177
      with a borderline AFI (>5 and <10 cm) and 562 with a normal AFI (>= 10-24 cm);
      360 patients delivered at University of Arizona Medical Center, and 379 delivered
      at St Joseph's Hospital. Combined and individual analyses of each center revealed
      no significant difference in fetal intolerance of labor (P = .19) or cesarean
      delivery for fetal intolerance (P = .074) between cohorts. In both settings,
      patients with a borderline AFI were more likely than those with a normal AFI to
      undergo antepartum testing (P < .001). A statistically significant increase in
      intrauterine growth restriction in the borderline AFI group was noted, with a
      calculated risk ratio of 13.76 (P < .001). There was no difference between groups
      for meconium-stained amniotic fluid (P = .23), neonatal intensive care unit
      admission (P = .054), preterm delivery (P = .31), or operative vaginal delivery
      (P = .45). CONCLUSIONS: The findings of this study suggest that there is no
      difference in the rate of fetal intolerance of labor in pregnancies with a
      borderline AFI and those with a normal AFI. Pregnancies complicated by a
      borderline AFI are more likely to undergo antepartum testing, yet the benefit is
      unclear. Significantly more patients with a borderline AFI had underlying growth
      restriction, which may provide a useful tool for risk stratification in the
      management of a borderline AFI.

PMID- 24658953
TI  - Effect of low-intensity pulsed ultrasound on bone regeneration: biochemical and
      radiologic analyses.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effects of low
      intensity pulsed ultrasound at 1.0 MHz on the healing process of fractures with
      bone loss in the rat fibula by alkaline phosphate level measurement and
      radiologic analyses. METHODS: Thirty 70-day-old male Wistar rats underwent a bone
      resection of 2.5 to 3.0 mm between the proximal and middle third of the right
      fibular diaphysis. The animals were randomly divided into 3 experimental groups:
      reference (uninjured), control (injured only), and treated (injured and treated
      with 5 applications of ultrasound, interspersed by 2 days of rest, beginning 24
      hours after the osteotomy). Euthanasia was performed at experimental periods of 7
      and 14 days. The right hind limb was removed for radiologic analysis. The blood
      was collected via cardiac puncture to determine the serum alkaline phosphatase
      activity. RESULTS: The bone fractures had not been completely consolidated in the
      treated and control group when analysis of the bone took place. At day 7, the
      serum alkaline phosphatase activity was higher in the treated group (mean +/- SD,
      72.17 +/- 7.02 U/L) compared to the control (65.26 +/- 8.41 U/L) and reference
      (67.21 +/- 7.86 U/L) groups. At day 14, higher alkaline phosphatase activity was
      seen in the control group (68.96 +/- 8.12 U/L) compared to the treated (66.09 +/-
      8.46 U/L) and reference (67.14 +/- 7.96 U/L) groups. CONCLUSIONS: The biochemical
      and radiologic results suggest that low-intensity pulsed ultrasound can be used
      as an auxiliary method to consolidate fractures and probably reduces the bone
      healing time, offering clinical benefits.

PMID- 24658954
TI  - Posterior thoracic echocardiography for assessment of native and prosthetic
      aortic valves in the presence of pleural effusion.
AB  - Many patients with aortic stenosis have difficult imaging windows due to advanced
      age, kyphosis, prior chest surgeries, radiation-induced skin changes, or
      hyperinflated lungs from pulmonary disease. Here we describe 4 cases to
      illustrate that in a subset of patients with pleural effusion, a posterior
      imaging approach can be used to obtain diagnostic images for native and
      prosthetic aortic valves. In these cases, nondiagnostic transthoracic
      echocardiographic images were obtained from conventional imaging windows, leading
      to inaccurate or incomplete assessment of the aortic valve. In all cases, images
      obtained from a posterior thoracic approach provided important additional
      diagnostic information. 

PMID- 24658955
TI  - Thyroid hemangiomas diagnosed on sonography.
AB  - Primary thyroid hemangiomas are extremely rare, and only a few cases have been
      previously reported. Primary hemangiomas are developmental anomalies resulting
      from the inability of the angioblastic mesenchyme to form canals. Thyroid
      hemangiomas are generally considered difficult to diagnose preoperatively because
      of their low incidence and nonspecific imaging findings. Here we report 2 cases
      of thyroid hemangiomas that were diagnosed correctly on preoperative sonography.
      Our cases showed similar sonographic findings, such as well-circumscribed
      hypoechoic lesions with internal channel-like linear lines, and bloody content
      was aspirated during fine-needle aspirations. Our report shows that thyroid
      hemangiomas can be diagnosed correctly by sonography with or without confirmation
      of bloody content in the lesions by fine-needle aspiration. 

PMID- 24658956
TI  - Personalized medicine in a patient with the antenatal diagnosis of an umbilical
      cord knot and a previous adverse outcome for this reason.

PMID- 24658957
TI  - Hypoplasia of the posterior mitral leaflet concurrent with a supravalvular mitral
      ring: a rare cause of congenital mitral stenosis.

PMID- 24658958
TI  - Incidental detection of an aortic stent endoleak with contrast-enhanced
      sonography.

PMID- 24658959
TI  - Reliability and validity of a quantitative color scale to evaluate masticatory
      performance using color-changeable chewing gum.
AB  - In the present study, we developed a novel color scale for visual assessment,
      conforming to theoretical color changes of a gum, to evaluate
      masticatoryperformance; moreover, we investigated the reliability and validity of
      this evaluation method using the color scale. Ten participants (aged 26.30 years)
      with natural dentition chewed the gum at several chewing strokes. Changes in
      color were measured using a colorimeter, and then, linearregression expressions
      that represented changes in gum color were derived. The color scale was developed
      using these regression expressions. Thirty-two chewed gums were evaluated using
      colorimeter and were assessed three times using the color scale by six dentists
      aged 25.27 (mean, 25.8) years, six preclinical dental students aged 21.23 (mean,
      22.2) years, and six elderly individuals aged 68.84 (mean, 74.0) years. The
      intrarater and interrater reliability of evaluations was assessed using
      intraclass correlation coefficients. Validity of the method compared with a
      colorimeter was assessed using Spearman's rank correlation coefficient. All
      intraclass correlation coefficients were > 0.90, and Spearman's rank-correlation
      coefficients were > 0.95 in all groups. These results indicated that the
      evaluation method of the color-changeable chewing gum using the newly developed
      color scale is reliable and valid. 

PMID- 24658960
TI  - Differences and similarities between father-infant interaction and mother-infant
      interaction.
AB  - The aim of this study was to compare father-infant interaction with mother-infant
      interaction, and explore differences and similarities between parents. Related
      factors for quality of father-infant interaction were also examined. Sixteen
      pairs of parents with infants aged 0 to 36 months were observed for play
      interaction between parents and their children. Results suggested no significant
      differences between parents, but children's interactions were significantly more
      contingent with fathers than mothers (p =.045). Significant correlations between
      parents were found in socialemotional growth fostering encouragement for children
      during interaction (rho =.73, p =.001). Paternal depressive symptoms were
      significantly correlated to paternal sensitivity to child's cues (rho =-.59, p
      =.017). 

PMID- 24658961
TI  - Vocal cord assessment with transnasal endoscopy in intubated patients after
      esophagectomy.
AB  - BACKGROUND: Vocal cord paralysis (VCP) is one of the postoperative complications
      after radical esophagectomy. VCP may also lead to serious morbidities such as
      respiratory distress and aspiration pneumonia. Therefore, an early diagnosis of
      VCP is meaningful in the postoperative management of patients undergoing
      esophagectomy. We evaluated a new practical method for diagnosing postoperative
      VCP. METHODS: The laryngeal assessment of 30 patients was performed, and the
      presence of VCP was inferred while the following 15 patients by endoscopy before
      extubation after performing consecutive radical esophagectomy in 45 esophageal
      cancer patients. The vocal cord mobility, including adduction and abduction, were
      assessed by inserting the tip of a transnasal endoscope near the vocal cord in
      the awake patients with orotracheal intubation on the first postoperative day.
      The presence of VCP was reevaluated after extubation. RESULTS: Eleven of the 30
      patients assessed after radical esophagectomy had unilateral VCP and one patient
      had bilateral VCP. The abduction findings were useful for assessing VCP and the
      sensitivity, specificity, positive and negative predictive values and accuracy
      were 97.9%, 100%, 100%, 92.9% and 98.3%, respectively. The results of the
      following 15 patients were closely similar. CONCLUSIONS: The VCP during
      orotracheal intubation is assessable by transnasal endoscopy.

PMID- 24658962
TI  - Development of oral and extra-oral endosseous craniofacial implants by using a
      mesh structure for connective tissue attachment.
AB  - Connective tissue attachment to a mesh structure incorporated on the surface of
      oral implants and extra-oral endosseous craniofacial implants (EOECI) was
      investigated. Two types of implants were prepared: TI and TI-Mesh. TI was
      composed of an upper and a lower component, both comprised of a titanium
      cylinder, which could be connected using a titanium screw. The composition of the
      TIMesh was similar, but the lower cylinder had a lateral groove that was covered
      with a titanium mesh. In animal experiments performed using rat calvaria, the
      lower component was first implanted and was left submerged for 3 weeks, then the
      upper component was mounted percutaneously. After an additional 2 weeks, each
      implant and the surrounding tissues were harvested and evaluated. Histological
      observations revealed collagen fibers originating from surrounding hypodermal
      tissues anchored to the mesh structures of the TI-Mesh whereas no such collagen
      fibers were observed around TI. Significantly greater values of the attachment
      strength, the thickness of the dermal tissue, the thickness of hypodermal tissue,
      and the attachment lengths were observed in TI-Mesh than those of TI. Thus
      connective tissue attachment with collagen fibers anchored to the mesh was
      achieved by incorporating mesh structures into the percutaneously placed
      implants. 

PMID- 24658963
TI  - Reconstruction of small diameter arteries using decellularized vascular
      scaffolds.
AB  - Although artificial vessels are available for large diameter arteries, there are
      no artificial vessels for small diameter arteries of < 4 mm. We created a
      decellularized vascular scaffold (length, 10 mm; outer diameter, 1.5 mm; inner
      diameter, 1.3 mm) from rat abdominal arteries. We measured the biomechanical
      characteristics of the scaffolds, implanted them to defects made in rat carotid
      arteries, and evaluated their patency and the endothelial cell linings. Silastic
      grafts were implanted as controls. The decellularized scaffolds demonstrated
      similar mechanical characteristics to normal arteries. All of the control grafts
      were occluded. Fibroblast-like cells were discovered in the thrombus, and fibrous
      organization was apparent. In contrast, patency of the grafts in 10 of 12 animals
      was observed 4 weeks after implantation. The internal cavity of the patent
      scaffold was completely lined by endotheliallike cells. Thus, the possibility of
      small artery reconstruction using decellularized scaffolds was demonstrated. 

PMID- 24658965
TI  - Theoretical and experimental examination of particle-particle interaction effects
      on induced dipole moments and dielectrophoretic responses of multiple particle
      chains.
AB  - Dielectrophoresis (DEP), an electrokinetic phenomenon based on particle
      polarizations in nonuniform electric fields, is increasingly employed for
      particle and cell characterizations and manipulations in microdevices. However,
      particle number densities are rarely varied and particle-particle interactions
      are largely overlooked, but both affect particle's effective polarizations by
      changing the local electric field, which directly impacts particle assembly into
      chains. This work examines theoretical and experimental particle-particle
      interactions and dielectrophoretic responses in nonuniform electric fields, then
      presents individual and chain velocities of spherical polystyrene microparticles
      and red blood cells (RBCs) under DEP forces in a modified quadruple electrode
      microdevice. Velocities are independently compared between 1, 2, 3, and 4
      polystyrene beads and RBCs assembled into chains aligned with the electric field.
      Simulations compared induced dipole moments for particles experiencing the same
      (single point) and changing (multiple points) electric fields. Experiments and
      simulations are compared by plotting DEP velocities versus applied signal
      frequency from 1 kHz to 80 MHz. Simulations indicate differences in the DEP force
      exerted on each particle according to chain position. Simulations and experiments
      show excellent qualitative agreement; chains with more particles experienced a
      decrease in the DEP response for both polystyrene beads and RBCs. These results
      advance understanding of the extent that induced dipole polarizations with
      multiple particle chains affect observed behaviors in electrokinetic cellular
      diagnostic systems.

PMID- 24658966
TI  - A systematic profile of clinical inhibitors responsive to EGFR  somatic amino
      acid mutations in lung cancer: implication  for the molecular mechanism of drug
      resistance and sensitivity.
AB  - Human epidermal growth factor receptor (EGFR) has become a well-established
      target for the treatment of patients with non-small cell lung cancer (NSCLC).
      However, a large number of somatic mutations in such protein have been observed
      to cause drug resistance or sensitivity during pathological progression, limiting
      the application of reversible EGFR tyrosine kinase inhibitor therapy in NSCLC. In
      the current work, we describe an integration of in silico analysis and in vitro
      assay to profile six representative EGFR inhibitors against a panel of 71
      observed somatic mutations in EGFR tyrosine kinase domain. In the procedure, the
      changes in interaction free energy of inhibitors with EGFR upon various mutations
      were calculated one by one using a rigorous computational scheme, which was
      preoptimized based on a set of structure-solved, affinity-known samples to
      improve its performance in characterizing the EGFR-inhibitor system. This method
      was later demonstrated to be effective in inferring drug response to the
      classical L858R and G719S mutations that confer constitutive activation for the
      EGFR kinase. It is found that the Staurosporine, a natural product isolated from
      the bacterium Streptomyces staurosporeus, exhibits selective inhibitory activity
      on the T790M and T790M/L858R mutants. This finding was subsequently solidified by
      in vitro kinase assay experiment; the inhibitory IC50 values of Staurosporine
      against wild-type, T790M and T790M/L858R mutant EGFR were measured to be 937, 12
      and 3 nM, respectively.

PMID- 24658967
TI  - Combinatorial treatment of acute spinal cord injury with ghrelin, ibuprofen, C16,
      and ketogenic diet does not result in improved histologic or functional outcome.
AB  - Because of the complex, multifaceted nature of spinal cord injury (SCI), it is
      widely believed that a combination of approaches will be superior to individual
      treatments. Therefore, we employed a rat model of cervical SCI to evaluate the
      combination of four noninvasive treatments that individually have been reported
      to be effective for acute SCI during clinically relevant therapeutic time
      windows. These treatments included ghrelin, ibuprofen, C16, and ketogenic diet
      (KD). These were selected not only because of their previously reported efficacy
      in SCI models but also for their potentially different mechanisms of action. The
      administration of ghrelin, ibuprofen, C16, and KD several hours to days
      postinjury was based on previous observations by others that each treatment had
      profound effects on the pathophysiology and functional outcome following SCI.
      Here we showed that, with the exception of a modest improvement in performance on
      the Montoya staircase test at 8-10 weeks postinjury, the combinatorial treatment
      with ghrelin, ibuprofen, C16, and KD did not result in any significant
      improvements in the rearing test, grooming test, or horizontal ladder. Histologic
      analysis of the spinal cords did not reveal any significant differences in tissue
      sparing between treatment and control groups. Although single approaches of
      ghrelin, ibuprofen, C16, and KD have been reported to be beneficial after SCI,
      our results show that the combination of the four interventions did not confer
      significant functional or histological improvements in a cervical model of SCI.
      Possible interactions among the treatments may have negated their beneficial
      effects, emphasizing the challenges that have to be addressed when considering
      combinatorial drug therapies for SCI.

PMID- 24658968
TI  - Regional variations in German mesothelioma mortality rates: 2000-2010.
AB  - PURPOSE: Germany has one of the highest age-adjusted mesothelioma mortality rates
      worldwide. As mesothelioma occurs >= 30 years after asbestos exposure,
      contemporary rates likely reflect exposures in the 1960-1970s. During this
      period, political division between West and East Germany led to differences
      regarding the import and consumption of asbestos. It is unclear whether
      mesothelioma rates also differ between these formerly separate countries which
      are now served by similar health and mortality reporting systems, thereby
      facilitating regional comparisons. METHODS: We examined regional, temporal, and
      sex variations in mesothelioma mortality rates in Germany in 2000-2010,
      collapsing the federal states into West Germany, East Germany, and Berlin. We
      calculated truncated (>= 40 years) age-standardized mesothelioma mortality rates
      (ASRs(40+)) per 100,000 person-years, estimated sex-stratified mortality rate
      ratios (MRRs) (95 % confidence intervals (CIs)), adjusted for age and calendar
      year from Poisson models, and fitted age-period-cohort models. RESULTS: There
      were 12,854 mesothelioma deaths at ages >= 40 years in Germany during 2000-2010.
      ASRs(40+) were higher in West (males 4.4; females 0.8) than East (males 1.7;
      females 0.6) Germany. MRRs for West versus East Germany were 2.68 (95 % CI 2.48
      2.88) among males and 1.42 (95 % CI 1.27-1.59) among females. In both regions,
      mortality rates increased for birth cohorts until the mid 1940s and subsequently
      declined. The country's peak mesothelioma burden is predicted to occur by 2020.
      CONCLUSIONS: Geographical differences in mesothelioma mortality rates are
      consistent with heterogeneous historical asbestos exposures. Differences may
      exist for other asbestos-related cancers and should be investigated in analytic
      studies with individual asbestos exposure information.

PMID- 24658969
TI  - Energy non-equipartition in strongly convective granular systems.
AB  - Using positron emission particle tracking, the effects of convective motion and
      the resulting segregative behaviour on the partition of kinetic energy between
      the components of a bidisperse granular system are, for the first time,
      systematically investigated. It is found that the distribution of energy between
      the two system components, which are equal in size but differ in their material
      properties, is strongly dependent on the degree of segregation observed in the
      granular bed. The results obtained demonstrate that the difference in energy
      obtained by dissimilar particle species is not an innate property of the
      materials in question, but can in fact be altered through variation of the
      relevant system parameters. The existence of a relationship between the
      convective and segregative properties of a granular system and the degree of
      energy equipartition within the system implies the possibility of extending
      existing theory into the convective regime. Thus, our findings represent an
      incremental step towards the definition of a granular analogy to temperature that
      can be applied to more generalised systems and, through this, an improved
      understanding of inhomogeneous granular systems in general. 

PMID- 24658970
TI  - Novel technique of repair of large tracheo-esophageal fistula  following battery
      ingestion in children: review of two cases.
AB  - Surgical repair of acquired tracheo-esophageal fistula may result in tracheal
      stenosis or esophageal stricture. We used fistula with esophageal cuff as flap to
      repair the tracheal defect. Esophageal repair was performed by rotating ends
      through 90 degrees  in opposite direction. This technique offers excellent repair
      in a single stage.

PMID- 24658972
TI  - Applications of homochiral metal-organic frameworks in enantioselective
      adsorption and chromatography separation.
AB  - Chiral separation is of great importance for drug development, pharmacology, and
      biology. Chiral metal-organic frameworks (MOFs) is a new class of porous solid
      materials with high surface area, large pore size, high chemical stability,
      uniformly structured cavities, and the availability of modification. The
      excellent properties of MOFs have attracted intense interest to explore their
      performance and mechanism in chiral separation. This review summarizes three
      synthetic strategies of chiral MOFs and their applications in enantioselective
      adsorption and chromatographic separation. All the experimental and molecular
      simulation results demonstrated that high enantioselectivity was strongly
      correlated with a close match between the size of the pore and chiral molecules. 

PMID- 24658971
TI  - Differential DNA methylation analysis of breast cancer reveals the impact of
      immune signaling in radiation therapy.
AB  - Radiotherapy (RT) is a central treatment modality for breast cancer patients. The
      purpose of our study was to investigate the DNA methylation changes in tumors
      following RT, and to identify epigenetic markers predicting treatment outcome.
      Paired biopsies from patients with inoperable breast cancer were collected both
      before irradiation (n = 20) and after receiving 10-24 Gray (Gy) (n = 19). DNA
      methylation analysis was performed by using Illumina Infinium 27K arrays.
      Fourteen genes were selected for technical validation by pyrosequencing. Eighty
      two differentially methylated genes were identified in irradiated (n = 11) versus
      nonirradiated (n = 19) samples (false discovery rate, FDR = 1.1%). Methylation
      levels in pathways belonging to the immune system were most altered after RT.
      Based on methylation levels before irradiation, a panel of five genes (H2AFY,
      CTSA, LTC4S, IL5RA and RB1) were significantly associated with clinical response
      (p = 0.041). Furthermore, the degree of methylation changes for 2,516 probes
      correlated with the given radiation dose. Within the 2,516 probes, an enrichment
      for pathways involved in cellular immune response, proliferation and apoptosis
      was identified (FDR < 5%). Here, we observed clear differences in methylation
      levels induced by radiation, some associated with response to treatment. Our
      study adds knowledge on the molecular mechanisms behind radiation response. 

PMID- 24658975
TI  - High-resolution melt as a screening method in autosomal dominant polycystic
      kidney disease (ADPKD).
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited
      condition caused by PKD1 and PKD2 mutations. Complete analysis of both genes is
      typically required in each patient. In this study, we explored the utility of
      High-Resolution Melt (HRM) as a tool for mutation analysis of the PKD2 gene in
      ADPKD families. METHODS: HRM is a mismatch-detection method based on the
      difference of fluorescence absorbance behavior during the melting of the DNA
      double strand to denatured single strands in a mutant sample as compared to a
      reference control. Our families were previously screened by linkage analysis.
      Subsequently, HRM was used to characterize PKD2-linked families. Amplicons that
      produced an overlapping profile sample versus wild-type control were not further
      evaluated, while those amplicons with profile deviated from the control were
      consequently sequenced. RESULTS: We analyzed 16 PKD2-linked families by HRM
      analysis. We observed ten different variations: six single-nucleotide
      polymorphisms and four mutations. The mutations detected by HRM and confirmed by
      sequencing were as follows: 1158T>A, 2159delA, 2224C>T, and 2533C>T. In
      particular, the same haplotype block and nonsense mutation 2533C>T was found in 8
      of 16 families, so we suggested the presence of a founder effect in our province.
      CONCLUSIONS: We have developed a strategy for rapid mutation analysis of the PKD2
      gene in ADPKD families, which utilizes an HRM-based prescreening followed by
      direct sequencing of amplicons with abnormal profiles. This is a simple and good
      technique for PKD2 genotyping and may significantly reduce the time and cost for
      diagnosis in ADPKD.

PMID- 24658973
TI  - Dynamics of inhibitory co-transmission, membrane  potential and pacemaker
      activity determine neuromyogenic  function in the rat colon.
AB  - Interaction of different neuromyogenic mechanisms determines colonic motility. In
      rats, cyclic depolarizations and slow waves generate myogenic contractions of low
      frequency (LF) and high frequency (HF), respectively. Interstitial cells of Cajal
      (ICC) located near the submuscular plexus (SMP) generate slow waves. Inhibitory
      junction potential (IJP) consists on a purinergic fast (IJPf) followed by a
      nitrergic slow (IJPs) component leading to relaxation. In the present study, we
      characterized (1) the dynamics of purinergic-nitrergic inhibitory co-transmission
      and (2) its contribution on prolonged inhibition of myogenic activity. Different
      protocols of electrical field stimulation (EFS) under different pharmacological
      conditions were performed to characterize electrophysiological and mechanical
      responses. Smooth muscle cells (SMCs) in tissue devoid of ICC-SMP had a resting
      membrane potential (RMP) of -40.7 +/- 0.7 mV. Single pulse protocols increased
      purinergic and nitrergic IJP amplitude in a voltage-dependent manner (IJPfMAX = 
      26.4 +/- 0.6 mV, IJPsMAX = -6.7 +/- 0.3 mV). Trains at increasing frequencies
      enhanced nitrergic (k = 0.8 +/- 0.2 s, IJPsinfinity = -15 +/- 0.5 mV) whereas
      they attenuated purinergic responses (k = 3.4 +/- 0.6 s,IJPfinfinity = -8.9 +/-
      0.6 mV). In tissues with intact ICC-SMP, the RMP was -50.0 +/- 0.9 mV and
      nifedipine insensitive slow waves (10.1 +/- 2.0 mV, 10.3 +/- 0.5 cpm) were
      recorded. In these cells, (1) nitrergic and purinergic responses were reduced and
      (2) slow waves maintained their intrinsic frequency and increased their amplitude
      under nerve-mediated hyperpolarization. Based on the co-transmission process and
      consistent with the expected results on RMP, prolonged EFS caused a progressive
      reduction of LF contractions whereas HF contractions were partially insensitive.
      In conclusion, inhibitory neurons modulate colonic spontaneous motility and the
      principles determining post-junctional responses are (1) the frequency of firing
      that determines the neurotransmitter/receptor involved, (2) the transwall
      gradient and (3) the origin and nature of each myogenic activity

PMID- 24658976
TI  - The gender-related differences of nutrient intakes in a group of Italian obese
      patients display the ongoing transition from Mediterranean to western dietary
      patterns.
AB  - BACKGROUND: The purpose of this study was to compare nutrients and energy intakes
      between obese women and men and the variation rates over or below the recommended
      dietary allowances. METHODS: A retrospective survey was conducted on the records
      of obese patients, categorized into gender-related groups (36 women, 36 men).
      Total energy and nutrient intakes were determined. RESULTS: The highest variation
      rates were found for animal protein, averaging 225 % over the recommended dietary
      allowance, without significant differences between women and men. The simple
      carbohydrate intake was quite elevated in women with variations almost 80% over
      the RDA, significantly higher than in men (22%). CONCLUSION: The consumption of
      high-protein foods in both sexes, and even more the association with high-simple
      carbohydrate foods in women, display the Westernization of traditional eating
      habits.

PMID- 24658978
TI  - Cheating in publications--self or others?

PMID- 24658977
TI  - Comparison of the morbidity, weight loss, and relative costs between robotic and
      laparoscopic sleeve gastrectomy for the treatment of obesity in Brazil.
AB  - BACKGROUND: In recent years, there has been renewed interest in using robotics in
      bariatric surgery for the treatment of morbid obesity. However, the high cost of
      a robotic surgical system has hindered its widespread use in developing
      countries. This study aims to compare the rate of morbidity, weight loss, and
      relative costs between laparoscopic (LSG) and robotic-assisted sleeve gastrectomy
      (RSG) performed for the treatment of obesity in a single center in Brazil.
      METHODS: From January 2011 to March 2013, 48 severely obese patients underwent
      either LSG or RSG at our institution and were prospectively followed up for 12
      months. Patients were free to choose either approach and were informed of any
      extra costs that may be incurred. RESULTS: Thirty-two patients underwent LSG and
      16 patients, RSG. No significant differences were observed between LSG and RSG
      groups regarding age, sex, BMI, incidence of comorbidities, duration of surgery,
      and length of hospital stay. Also, there were no significant between-group
      differences in BMI values evaluated at 6 and 12 months after surgery. Surgical
      costs were almost twice as high and total hospital costs were approximately 50 %
      higher in the robotic approach compared to the laparoscopic approach. CONCLUSION:
      Both RSG and LSG had excellent and similar post-operative clinical outcomes.
      However, the much higher costs of purchasing and maintaining the robotic system
      are still precluding the use of RSG as a routine approach in the treatment of
      morbid obesity in Brazil.

PMID- 24658979
TI  - Acceleration of skin wound healing with tragacanth (Astragalus) preparation: an
      experimental pilot study in rats.
AB  - Gum tragacanth is a natural complex mixture of polysaccharides and alkaline
      minerals extracted from species of Astragalus plant, which is found widely in
      arid regions of the Middle East. In a pilot experimental study we examined the
      effects of its topical application on wound healing in ten albino adult male
      rats. Two similar parasagittal elliptical full-thickness wounds (control vs. test
      samples) were created on the dorsum of each animal. Test group samples were fully
      covered by a thin layer of gum tragacanth daily. The extent of wound healing was
      evaluated by planimetric analysis on multiple occasions during the 10-day study
      period. On the 7th day of the study, the percent of wound closure was
      significantly higher in gum tragacanth-treated specimens compared to the control
      samples (87%+/-2% vs. 70%+/-4%, P<0.001). The majority of wounds in the test
      group were completely closed by the 10th day of the study. The difference in
      wound healing index measured by histological examination on day 10 of the study
      was also statistically meaningful between the two groups (0.624+/-0.097 vs.
      0.255+/-0.063, P<0.05). The results of this study clearly showed the useful
      effects of topical application of gum tragacanth in acceleration of skin wound
      contraction and healing. More studies are encouraged to identify the implicating
      agents and precisely understand the mechanism by which they exert their wound
      healing effects. 

PMID- 24658980
TI  - The effect of EFG1 gene silencing on down-regulation of SAP5 gene, by use of RNAi
      technology.
AB  - Efg1 transcription factor is believed to be the main regulator of hyphal
      formation under many different conditions. In addition, it is responsible for
      positive regulation of the expression of several hyphal-specific genes. SAP5,
      which encodes secreted aspartic proteinase, is one of the mentioned genes and is
      crucial for pathogenicity properties. In the present work we have established the
      experimental conditions for the use of siRNA in the diploid yeast Candida
      albicans in order to knock-down the EFG1 gene expression as well as the Efg1
      dependent gene, SAP5. The 19-nucleotide siRNA was designed according to cDNA
      sequence of EFG1 gene in C. albicans and modified-PEG/LiAc method was applied for
      yeast transfection. To quantify the level of both EFG1 and SAP5 gene expression,
      the cognate mRNAs were measured in C. albicans by quantitative real-time RT-PCR
      and data was consequently analyzed by use of REST(r) software. Images taken by
      fluorescent microscopy method indicated the effectiveness of transfection.
      According to REST(r) software data analysis, expression of EFG1 gene decreased
      about 2.5-fold using 500 nM of siRNA. A 7-fold decrease in EFG1 gene expression
      was observed when applying 1 uM of siRNA (P<0.05). Consequently, the expression
      of SAP5 was significantly down-regulated both in yeast treated with 500 and 1000
      nM of siRNA (P<0.05). In conclusion, post-transcriptional gene silencing (PTGS)
      is likely to be considered as a promising approach to discover new gene targets
      so as to design fungal-specific antifungal agents, and it is strongly possible
      that we are taking the right way to battle with C. albicans-associated
      infections. 

PMID- 24658981
TI  - Evaluation of in-hospital NT-proBNP changes in heart failure patients to identify
      the six-month clinical response following cardiac resynchronization therapy.
AB  - N-terminal pro beta-type natriuretic peptide (NT-proBNP) is a valuable marker for
      monitoring the response to treatment in patients with heart failure. Based on the
      clinically observed improvement of heart failure symptoms early after cardiac
      resynchronization therapy (CRT), we sought to investigate whether CRT induce any
      significant reduction in the plasma level of NT-proBNP in three days after
      implantation and whether it is correlated with patients' response at six months.
      In this prospective study, 21 consecutive patients with severe heart failure (New
      York Heart Association class 3.19+/-0.40) who underwent CRT were enrolled. Being
      alive, no hospitalization due to decompensated heart failure, and improvement of
      at least one NYHA functional class at six months were classified as clinical
      responsiveness. The plasma level of NT-proBNP was measured before, three days,
      and six months after CRT. Clinical evaluation, echocardiographic study, and six
      minute walking test were performed before and six months after the procedure. At
      six months' follow-up, 16 (76.2%) patients were responders. The plasma level of
      NT-proBNP at three days after CRT increased almost equally in both responder and
      non-responder groups of patients (?NT-proBNP was 40.94+/-135.74 vs. 54.80+/
      88.98); however, at six months' follow-up, the NT-proBNP changes statistically
      differed across the two groups of patients (P=0.005). According to our findings,
      NT-proBNP percent deviation from baseline to three days after CRT appears to be
      not correlated with the patients' clinical response after six months, which was
      incongruent to the patients' clinical improvement after CRT. 

PMID- 24658982
TI  - Patient's rights charter in Iran.
AB  - Given the importance of patient's rights in healthcare, special attention has
      been given to the concept of patient's rights by the Ministry of Health and
      Medical Education in Iran. Iranian patient's rights charter has been compiled
      with a novel and comprehensive approach. This charter aims to elucidate rights of
      recipients of health services as well as observing ethical standards in medicine.
      This paper presents the Iranian patient's rights charter. Based on a study done
      from 2007 to 2009, the charter has been finalized through an extensive
      consultation involving all stakeholders, patients, physicians, nurses, lawyers,
      patient associations and health policy makers. The developed charter was adopted
      by the Ministry of Health in December 2009. Iranian patient's rights charter has
      been formulated in the framework of 5 chapters and 37 articles including vision
      and an explanatory note. The five chapters concern right to receiving appropriate
      services, right to access desired and enough information, right to choose and
      decide freely about receiving healthcare, right to privacy and confidentiality,
      and finally right to access an efficient system of dealing with complaints which
      have been explained in 14, 9, 7, 4 and 3 articles, respectively.  The paper
      concludes that, adopting the patient's rights charter is a valuable measure to
      meet patient's rights; however, a serious challenge is how to implement and
      acculturate observing patient's rights in practice in our healthcare system in
      Iran. 

PMID- 24658983
TI  - Possible role for growth hormone in suppressing acylated ghrelin and hunger
      ratings during and after intermittent exercise of different intensities in obese
      individuals.
AB  - Body weight is influenced by both food intake and energy expenditure. Acylated
      ghrelin enhances appetite, and its circulating level is suppressed by growth
      hormone. Data on the acylated ghrelin responses to exercise of different
      intensities in obese individuals are currently not available. This study examined
      the effects of an intermittent exercise protocol on acylated ghrelin levels and
      hunger ratings in obese people. Nine inactive male ran on the treadmill at 0900
      with progressive intensities of 50, 60, 70, and 80% of VO2max for 10, 10, 5, and
      2 min respectively. Blood samples were collected before the exercise at 0845 (-15
      min as the resting values), after each workload (10, 23, 31, and 36 min during
      exercise), and at 30, 60, and 120 min thereafter. The control trial was conducted
      under identical conditions with the exception of exercise. Compared to the
      baseline, both acylated ghrelin levels and hunger ratings were suppressed at 70%
      of VO2max during exercise (17.74 vs. 9.80 pmol/L and 4.84 vs. 2.96 unit
      respectively) and remained significantly lower than the control trial 2 h after
      the cessation of exercise (13.95 vs. 20.32 pmol/L and 3.33 vs. 6.04 unit,
      respectively). Growth Hormone increased during the exercise period and peaked at
      80% of VO2max. These findings indicate that acylated ghrelin concentrations and
      hunger ratings are suppressed during exercise and two hours thereafter in obese
      individuals, and it is possible that Growth Hormone caused the suppression of
      acylated ghrelin.

PMID- 24658984
TI  - Evaluation of febrile neutropenia in patients undergoing hematopoietic stem cell
      transplantation.
AB  - The aim of this study was to determine the incidence and causes of fever as a
      major problem contributing to transplantation related mortality among patients
      undergoing hematopoietic stem cell transplantation (HSCT) and evaluation of
      antibiotic use, according to reliable guidelines.We retrospectively reviewed
      hospital records of 195 adult patients who underwent HSCT between 2009-2011 at
      hematology-oncology and bone marrow transplantation research center. Baseline
      information and also data related to fever and neutropenia, patient's outcomes,
      duration of hospitalization and antibiotic use pattern were documented.A total of
      195 patients were analyzed and a total of 268 febrile episodes in 180 patients
      were recorded (mean 1.5 episodes per patient). About 222 episodes (82%) were
      associated with neutropenia which one-fourth of them were without any documented
      infection sources. Microbiologic documents showed that the relative frequencies
      of gram positive and gram negative bacteria were 62.5% and 37.5%, respectively.
      The hospital stay duration was directly related to the numbers of fever episodes
      (P<0.0001).The rate of febrile episodes in autologous stem cell transplantation
      was significantly higher compared to allogeneic type (P<0.05).It is necessary to
      determine not only the local profile of microbiologic pattern, but also
      antibiotic sensitivities in febrile neutropenic patients following hematopoietic
      stem cell transplantation, and reassess response to antibiotic treatment to
      establish any necessity for modifications to treatment guidelines in order to
      prevent any fatal complications from infection. 

PMID- 24658985
TI  - Evaluation of the effects of resting in appearance of post lumbar puncture
      headache.
AB  - Lumbar puncture (LP) is a procedure for obtaining spinal fluid from spinal
      meningeal spaces this can be done as a diagnostic or therapeutic procedure which
      can result in to a typical positional headache named as post lumbar puncture
      headache .This can cause a lot of discomforts for patients and makes fear from
      the procedure. This study designed to evaluate the effect of resting position
      after LP on post lumbar puncture headache (PLPH). Patients who had a diagnostic
      lumbar puncture were divided randomly in two groups .Group A patients had one
      hour rest in the supine position while group B patients had one hour rest in the
      prone position. Both groups followed for appearance of symptoms of PLPH for 5
      days. 119 patients completed the study, 57 (48%) male patients and 62 (52%)
      female .PLPH totally appeared in 38 (31.9%) patients .In the group A PLPH was
      present in 20 patients whereas in group B it was present in 18 patients.
      Statistical analysis showed no significant differences between two groups
      (P>0.07). Position of rest after LP has no significant effect on reducing post
      lumbar puncture headache and there is no need to emphasize on position of rest
      after LP. 

PMID- 24658986
TI  - Bipolar disorder in women with polycystic ovarian syndrome (PCO).
AB  - This study was designed to determine the prevalence of bipolar disorder in women
      with polycystic ovarian syndrome (PCO). One hundred and ten women with definite
      diagnosis of PCO and one hundred and ten age-matched infertile women due to other
      reasons except for PCO were enrolled in this case-control study. Ten ml fasting
      venous blood sample obtained to measure fasting glucose, LH and FSH. Height,
      weight and waist-to-hip ratio (WHR) were also recorded by an expert technician. A
      psychiatrist examined all 220 cases in order to determine the prevalence of
      depression and bipolarity. Mean age of each group participants were not
      significantly different while FBS, LH and LH/FSH levels were significantly higher
      in PCO patients. Eighty eight case were depressed in PCO group while 96 were
      depressed in control group (P=0.03). Bipolar disorder were higher in PCO group in
      comparison with controls (8 vs. 0, P=0.004). Psychiatric disorders should be
      considered in PCO women. 

PMID- 24658964
TI  - Older patients with chronic myeloid leukemia (>=65 years) profit more from higher
      imatinib doses than younger patients: a subanalysis of the randomized CML-Study
      IV.
AB  - The impact of imatinib dose on response rates and survival in older patients with
      chronic myeloid leukemia in chronic phase has not been studied well. We analyzed
      data from the German CML-Study IV, a randomized five-arm treatment optimization
      study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic
      phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day
      (IM800) and stratified according to age (>=65 years vs. <65 years) were compared
      regarding dose, response, adverse events, rates of progression, and survival. The
      full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day.
      The dose could then be reduced according to tolerability. A total of 828 patients
      were randomized to IM400 or IM800. Seven hundred eighty-four patients were
      evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and
      83 (21 %) on IM800 were >=65 years. The median dose per day was lower for
      patients >=65 years on IM800, with the highest median dose in the first year (466
      mg/day for patients >=65 years vs. 630 mg/day for patients <65 years). Older
      patients on IM800 achieved major molecular remission and deep molecular remission
      as fast as younger patients, in contrast to standard dose imatinib with which
      older patients achieved remissions much later than younger patients. Grades 3 and
      4 adverse events were similar in both age groups. Five-year relative survival for
      older patients was comparable to that of younger patients. We suggest that the
      optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov
      identifier: NCT00055874

PMID- 24658987
TI  - Association of ADHD symptoms severity with higher paternal and lower maternal age
      of a clinical sample of children.
AB  - This study examines the association of father's and mother's age with the
      severity of inattention and hyperactivity/impulsivity. Participants are 470
      children with attention deficit hyperactivity disorder (ADHD) diagnosed according
      to DSM-IV diagnostic criteria. Moreover, parents reported the severity of ADHD
      symptoms through completing ADHD checklist. Mother's and father's age was
      associated with the score of hyperactivity/impulsivity. Lower father's age and
      advanced maternal age are associated with higher severity of
      hyperactivity/impulsivity in children and adolescents with ADHD. None of mothers'
      and fathers' age is associated with ADHD inattentiveness severity in children.
      Maternal and paternal education levels are not associated with ADHD severity.
      Older mothers and younger fathers have ADHD children with higher
      hyperactivity/impulsivity severity. It should be investigated whether the
      father's and mother's age are risk factors for ADHD. 

PMID- 24658988
TI  - Gender difference in clinical presentation of Turkish patients with pulmonary
      tuberculosis.
AB  - The study was aimed to investigate the diagnostic differences between male and
      female patients in pulmonary tuberculosis in a tertiary 660 bedded Educational
      Respiratory Medicine Hospital, Istanbul, Turkey. A retrospective study was
      conducted with the new diagnosed, 50 men and 50 female pulmonary tuberculous
      patients. Age, symptoms, personal history, radiologic and sputum smear findings
      were collected from their files. 44 male and 42 female patients were enrolled to
      the study. Male patients tended to be older, smoke more, get alcohol more, lose
      weight more and have sputum smear positivity more than the female patients.
      Neither the time of diagnosis nor the radiologic appearance differed
      statistically. The radiologic appearance, not the clinic symptoms, help to
      diagnose tuberculosis in female patients; especially in those with no weight loss
      and sputum smear negativity.

PMID- 24658989
TI  - Lead concentration in breast milk of lactating women who were living in Tehran,
      Iran.
AB  - It is obvious that lead intake is of concern not for its beneficial/essential
      effects on metabolism, but rather for its toxic actions, which can be especially
      damaging to children. The objective of this study was to analyze the
      concentration of lead in milk of mothers during prolonged lactation. Milk samples
      from 43 mothers were collected at 2 months postpartum. Lead was analyzed using
      atomic absorption spectrophotometer. The value of lead in human milk was 23.66+/
      22.43 MUg/l. Lead concentration in human milk of mothers was higher than other
      countries and no significant relationship was found between levels of human milk
      lead and mother's education, age, parity, height and weight. The concentrations
      of lead in the milk samples were high, which makes a major public health hazard
      for the inhabitants, especially neonatal and children, of the industrial
      locations. 

PMID- 24658990
TI  - An Iranian scoring system for diagnosing Buerger's disease.
AB  - Buerger's disease or thromboangiitis obliterans (TAO) seems to be common in IR
      Iran, The present study aimed to evaluate an Iranian population with Buerger's
      disease in order to suggest a diagnostic criterion for Buerger's disease based on
      the most frequent findings and to compare it with Papa diagnostic criteria. In a
      cross-sectional study, all patients with resting limb pain, limb ischemic ulcers,
      intermittent claudication and limb ischemia who referred to the Vascular Clinic
      of Sina Hospital during 2009-2011 were evaluated. The patients were allocated to
      Buerger's and non-Buerger's groups; Evaluating 122 patients (61 in each group),
      according to the model each clinical manifestations and risk factors in the
      patients with Buerger's disease obtained a score. Absent pulsation, abnormal
      distal Doppler sonography and ischemic ulcer were respectively present in 58
      (95.1%), 58 (95.1%) and 49 (80.3%) individuals with Buerger's disease.
      Multivariate linear regression analysis and multivariate logistic regression
      analysis were used for modeling. Considering the model finding findings,
      diagnostic criteria including age, sex, smoking, Raynaud's phenomenon, abnormal
      proximal Doppler, diabetes mellitus and hyperlipidemia were suggested (R2=0.582);
      the sensitivity and specificity of the criteria was respectively 95.1% and 78.7%.
      Compared with Papa criteria, Kappa coefficient was measured at 0.66 with a P
      value<0.001. It seems that the recommended criteria have an acceptable accuracy
      in diagnosing Buerger's disease, especially in the Iranian population; however,
      it is necessary to conduct more studies with larger sample sizes to evaluate the
      criteria, especially in other populations. 

PMID- 24658991
TI  - Psychometric properties of the Persian language version of Obsessive Beliefs
      Questionnaire (OBQ-44) in Iranian general population.
AB  - The Obsessive Beliefs Questionnaire-44 (OBQ-44), a self-report measure, was
      developed by the Obsessive Compulsive Cognitions Working Group (OCCWG) to assess
      beliefs considered relevant in the etiology and maintenance of obsessions and
      compulsions. The purpose of this study was to evaluate the psychometric
      properties of the Persian language version of the Obsessive Beliefs Questionnaire
      (POBQ-44). A sample of 222 medical students from an Iranian university was used
      to assess the reliability and validity of the POBQ-44. The results indicated five
      factors: 1) general, 2) perfectionism, certainty, 3) responsibility and threat
      estimation, 4) importance and control of thoughts, 5) complete performance. Each
      of these factors was found to have adequate test-retest and internal consistency
      reliability. Each of the factors was associated with O-C symptoms. In addition,
      adequate convergent validity was found with a measure of obsessive compulsive
      symptoms, and discriminate validity was found with measures of depression and
      anxiety. 

PMID- 24658992
TI  - Bibliographic search of publication patterns in rational use of drugs in Iran: a
      systematic approach.
AB  - Inappropriate use of drugs is a widespread problem with serious consequences such
      as increased adverse drug reaction and antimicrobial resistance. Proper
      interventions would have important financial and public health benefits. Several
      studies have been performed about Rational Drug Use (RUD) in Iran. To provide a
      picture of researches were done about RUD and highlight the existing gaps in
      practice in Iran, a systematic search was conducted by reviewing all papers
      (English and Persian) found by searching keywords in Pubmed, Web of Science,
      Google Scholar, CINAHL, Proquest, International Pharmaceutical Abstract (IPA),
      SID, Iran Medex and MagIran. Retrieved articles were extracted in Access form and
      exported to Excel for further analysis. After excluding duplicate and irrelevant
      articles, 466 related articles were remained. Number of publications increased
      dramatically after 2001. About 73% of studies were cross-sectional. Evaluation of
      prescribing pattern (15%), self-medication (11.3%) and adverse drug reaction
      (9.1%) were among the top topics which were studied. Despite an increasing trend
      in RUD publications in Iran, still large gaps remain to be investigated. Knowing
      the existing gaps is crucial for policy makers to make investments to solve the
      problems. 

PMID- 24658993
TI  - Hypopituitarism in a neonate with hyperbilirubinemia and decreased level of
      consciousness: a case report study.
AB  - Decreased level of consciousness in neonates may result from different
      etiologies, including rare metabolic and hormonal disorder due to anterior
      pituitary insufficiency. In this case report, a five-day-old newborn boy was
      referred to the neonatal intensive care unit of Mustafa Khomeini hospital of
      Ilam, Iran. He had an open anterior fontanel with no history of prenatal and
      familial diseases. Clinical examination showed decreased level of consciousness
      so that this patient responded only to painful stimuli. Furthermore,
      unconsciousness, hyperbilirubinemia, and hypotonia were fully evident. Given the
      clinical findings and decreased level of consciousness, hormonal diagnostic tests
      and brain CT scan were performed for any evidence of hypopituitarism. Clinical
      and experimental findings were consistent with the generalized edema and
      pituitary insufficiency secondary to central hypothyroidism and cortisol
      deficiency. Based on the findings, the neonate was put on the hormonal
      replacement therapy and, as the result, all of the abnormal clinical symptoms
      disappeared. In conclusion, fatal neonatal diseases may be mistaken with
      unimportant clinical findings at the first examination. Therefore, comprehensive
      attention to all potential causes of such symptoms in the neonates should be
      given for early diagnosis and treatment, and to prevent any fatal and
      irreversible complications. 

PMID- 24658994
TI  - Yunis-Varon syndrome: the first report of two Iranian cases.
AB  - The Yunis-Varon syndrome represents a rare autosomal recessive syndrome of easy
      recognition characterized by defective growth of the cranial bone along with
      complete or partial absence of the clavicles (cleidocranial dysplasia), absence
      of thumbs and halluces, distal aphalangia, ectodermal anomalies, growth
      retardation and poor outcome. The molecular genetic basis is unknown. Here, we
      report an 8 months old girl with Yunis-Varon syndrome, born to a consanguineously
      married, with normal parents. She had micrognathia, wide fontanels, prominent
      eyes, poor sucking, congenital heart diseases, asymmetric face, ambiguous
      genitalia, reduction anomaly in right hand including thumb, and hypoplastic
      distal phalanges of 3th fingers, and hypo plastic clavicles. She has glaucoma and
      lenses opacity. There is another similar case in her family. Karyotype is normal.
      She is the first Iranian known case of Yunis-Varon syndrome.

PMID- 24658995
TI  - Ectopic decidual reaction mimicking irritable bowel syndrome: a case report.
AB  - Ectopic decidualization with gross involvement of the peritoneum is one of the
      rare findings in pregnant women particularly when ectopic decidualization
      disseminated as an asymptomatic intra-abdominal nodule. We present here a case of
      an ectopic decidualization in a 33-year-old pregnant woman with symptoms of
      irritable bowel syndrome during pregnancy. 

PMID- 24658996
TI  - Genetics of neoplasia: inherited monogenic defects associated with cancers.

PMID- 24658997
TI  - Scallop protein with endogenous high taurine and glycine content  prevents high
      fat, high-sucrose-induced obesity and improves  plasma lipid profile in male
      C57BL/6J mice.
AB  - High-protein diets induce alterations in metabolism that may prevent diet-induced
      obesity. However, little is known as to whether different protein sources
      consumed at normal levels may affect diet-induced obesity and associated co
      morbidities. We fed obesity-prone male C57BL/6J mice high-fat, high-sucrose diets
      with protein sources of increasing endogenous taurine content, i.e., chicken,
      cod, crab and scallop, for 6 weeks. The energy intake was lower in crab and
      scallop-fed mice than in chicken and cod-fed mice, but only scallop-fed mice
      gained less body and fat mass. Liver mass was reduced in scallop-fed mice, but
      otherwise no changes in lean body mass were observed between the groups. Feed
      efficiency and apparent nitrogen digestibility were reduced in scallop-fed mice
      suggesting alterations in energy utilization and metabolism. Overnight fasted
      plasma triacylglyceride, non-esterified fatty acids, glycerol and hydroxy
      butyrate levels were significantly reduced, indicating reduced lipid mobilization
      in scallop-fed mice. The plasma HDL-to-total-cholesterol ratio was higher,
      suggesting increased reverse cholesterol transport or cholesterol clearance in
      scallop-fed mice in both fasted and non-fasted states. Dietary intake of taurine
      and glycine correlated negatively with body mass gain and total fat mass, while
      intake of all other amino acids correlated positively. Furthermore taurine and
      glycine intake correlated positively with improved plasma lipid profile, i.e.,
      lower levels of plasma lipids and higher HDL-to-total-cholesterol ratio. In
      conclusion, dietary scallop protein completely prevents high-fat, high-sucrose
      induced obesity whilst maintaining lean body mass and improving the plasma lipid
      profile in male C57BL/6J mice.

PMID- 24658998
TI  - Immobilized papain on gold nanorods as heterogeneous biocatalysts.
AB  - Papain, a thiol protease present in the latex of Carica papaya, is an enzyme
      which exhibits broad proteolytic activity, and, for this reason, it is utilized
      in a variety of industrial applications. Immobilization of papain on gold
      nanoparticles highly preserves its activity and enhances the stability, allowing
      the reuse of the linked enzyme many times without any significant loss of its
      catalytic performance. In particular, kcat and KM values remain substantially
      unchanged, while immobilized form shows a higher activity on a wider pH range
      retains 80 % residual activity also at 90  degrees C and shows higher
      functionality than the free form when incubated for long time (1 h) at 90 
      degrees C and at extreme pH values (3 and 12). A higher activity of immobilized
      papain with respect to the free form in the presence of various bivalent metal
      ions, known as strong inhibitors of papain, was also found. The reasons of this
      enhanced stability of gold nanorods immobilized papain are discussed.

PMID- 24658999
TI  - Improving amino acid nutrition to prevent intrauterine growth  restriction in
      mammals.
AB  - Intrauterine growth restriction (IUGR) is one of the most common concerns in
      human obstetrics and domestic animal production. It is usually caused by
      placental insufficiency, which decreases fetal uptake of nutrients (especially
      amino acids) from the placenta. Amino acids are not only building blocks for
      protein but also key regulators of metabolic pathways in fetoplacental
      development. The enhanced demands of amino acids by the developing conceptus must
      be met via active transport systems across the placenta as normal pregnancy
      advances. Growing evidence indicates that IUGR is associated with a reduction in
      placental amino acid transport capacity and metabolic pathways within the
      embryonic/fetal development. The positive relationships between amino acid
      concentrations in circulating maternal blood and placental amino acid transport
      into fetus encourage designing new therapies to prevent or treat IUGR by
      enhancing amino acid availability in maternal diets or maternal circulation.
      Despite the positive effects of available dietary interventions, nutritional
      therapy for IUGR is still in its infancy. Based on understanding of the
      underlying mechanisms whereby amino acids promote fetal growth and of their
      dietary requirements by IUGR, supplementation with functional amino acids (e.g.,
      arginine and glutamine) hold great promise for preventing fetal growth
      restriction and improving health and growth of IUGR offspring.

PMID- 24659000
TI  - The differential influences of positive affect, random reward, and performance
      contingent reward on cognitive control.
AB  - Growing evidence suggests that positive affect and reward have differential
      effects on cognitive control. So far, however, these effects have never been
      studied together. Here, the authors present one behavioral study investigating
      the influences of positive affect and reward (contingent and noncontingent) on
      proactive control. A modified version of the AX-continuous performance task,
      which has repeatedly been shown to be sensitive to reward and affect
      manipulations, was used. In a first phase, two experimental groups received
      either neutral or positive affective pictures before every trial. In a second
      phase, the two halves of a given affect group additionally received,
      respectively, performance-contingent or random rewards. The results replicated
      the typical affect effect, in terms of reduced proactive control under positive
      as compared to neutral affect. Also, the typical reward effects associated with
      increased proactive control were replicated. Most interestingly, performance
      contingent reward counteracted the positive affect effect, whereas random reward
      mirrored that effect. In sum, this study provides first evidence that performance
      contingent reward, on the one hand, and positive affect and performance
      noncontingent reward, on the other hand, have oppositional effects on cognitive
      control: Only performance-contingent reward showed a motivational effect in terms
      of a strategy shift toward increased proactive control, whereas positive affect
      alone and performance-noncontingent reward reduced proactive control. Moreover,
      the integrative design of this study revealed the vulnerability of positive
      affect effects to motivational manipulations. The results are discussed with
      respect to current neuroscientific theories of the effects of dopamine on affect,
      reward, and cognitive control.

PMID- 24659001
TI  - An explanation for the difference in the percutaneous penetration behavior of
      tamsulosin induced by two different O-acylmenthol derivatives.
AB  - Using tamsulosin (TAL) as a model drug, the aim of this study was to investigate
      and compare the percutaneous permeation behavior of two menthol derivatives, 2
      isopropyl-5-methylcyclohexyl heptanoate (M-HEP) and 2-isopropyl-5
      methylcyclohexyl decanoate (M-DEC). In vitro transdermal permeation study was
      carried out using porcine skin. The residual amount of enhancers in the skin
      after permeation experiment was determined by gas chromatographic (GC) method.
      The penetration depths of fluorescein were visualized by two-photon confocal
      laser scanning microscopy (2P-LSM) after the skin being treated with different
      enhancers. Furthermore, changes in the stretching frequency of functional group
      of ceramide were investigated by using attenuated total reflectance Fourier
      transform infrared (ATR-FTIR) technique. After M-HEP addition, the cumulative
      amount of TAL permeated in 8 h (Q8) reached 20.57+/-0.54 MUg/cm2 and the depth of
      fluorescein was 40 MUm; the CH2 of ceramide symmetric stretching frequency was 4
      cm-1 blue shifted. However, M-DEC has an opposite effect on TAL permeation
      compared with that of M-HEP. TAL is a crucial factor affecting permeation
      procedure, and microenvironment of lipid region determines promotion capability
      of the enhancers.

PMID- 24659017
TI  - Interstitial amino acid concentrations in rodent brain tissue during chemical
      ischemia.
AB  - The significance of electrophysiological phenomena is well validated in brain
      ischemia research. A close link with interstitial amino acid levels has not been
      proved convincingly but is generally assumed. This has given widespread rise to
      the clinical method of amino acid, especially glutamate, microdialysis. We
      combined microdialytic and electrophysiological techniques in an in vitro
      ischemia model to test for such a correlation. Rodent hippocampal brain slices
      were subjected to various patterns of ischemic simulation by depletion of glucose
      and oxygen and to K+ superfusion, which is often used as an alternative stressor.
      Our data do not strengthen the significance of clinically standardized glutamate
      measurements, insofar as ischemia-induced damage was demonstrated by
      electrophysiology and histology before being clearly mirrored by interstitial
      glutamate levels. Taurine would be a more promising candidate. K+ is not an
      adequate substitute for ischemic simulation, because biochemical and
      electrophysiological reactions of the tissue are clearly different. In vitro
      microdialysis during ischemic simulation is feasible and might provide a tool to
      inquire into glial functions during ischemic stress. It is probably not able to
      elucidate processes within the synaptic cleft.

PMID- 24659018
TI  - Did the corporatization of Portuguese hospitals significantly change their
      productivity?
AB  - This paper aims to investigate if the market structure reforms in the Portuguese
      health system have improved hospital performance and productivity. A robust non
      parametric Malmquist index is applied to measure group performance. The
      significance of the results achieved is examined using a conditional and non
      conditional subsampling bootstrapped-based methodology, enhanced by the
      likelihood cross validation criterion based on the k-nearest neighbors method.
      The sample contains information about 216 non-corporatized and 176 corporatized
      Portuguese hospitals for the period 2002-2009. Five models were applied, based on
      three study dimensions (internment, emergencies and doctor visits). The results
      show that although corporatized hospitals presented the highest efficiency
      consistency, they had also the lowest levels of productivity, while the hospitals
      under the traditional administrative public management system were the ones with
      the best average performance. However, several best practices were also found in
      all groups, being the limited companies were often dominated by both
      noncorporatized and public enterprise entities. Consistent output ranges where
      all groups present dominance over the others were also identified. It was
      possible to conclude that the more autonomy the hospital had from the Ministry of
      Health, the lower was its productivity.

PMID- 24659019
TI  - Transforming EQ-5D utilities for use in cost-value analysis of health programs.
AB  - In a number of jurisdictions there is increasing interest in incorporating
      concerns for fairness in models for economic evaluation of health interventions.
      Cost-value analysis is a name for evaluations with such a broader aim. The most
      widely held concern for fairness is a concern for the worse off, i.e. the idea
      that severity of illness should count in determining priorities. In economic
      evaluations of improvements in health-related quality of life this concern may be
      taken into account by replacing conventional health state utilities with societal
      values for health states that are characterised by strong upper end compression
      and decreasing marginal value of utility gains. We review evidence on the
      strength of concerns for the worse off--measured at the cardinal level--in 15
      articles published in peer-reviewed journals in the time period 1978-2010, with
      reports from altogether 20 individual studies in nine different countries. We
      report 116 individual observations of paired comparisons of utility improvements
      with different start levels. Concerns for severity show up quite strongly across
      countries, sample types and question framings. By means of regression analyses we
      fit a societal value function to the data that has the property of decreasing
      marginal value of utility gains. Using the central tendency in the data we
      present two plausible transformations of EQ-5D utilities into societal values
      that reflect concerns for the worse off.

PMID- 24659020
TI  - A greater number of euploid blastocysts in a given cohort predicts  excellent
      outcomes in single embryo transfer cycles.
AB  - PURPOSE: This multicentered retrospective study analyzed whether the quantity of
      euploid blastocysts in a given cohort after comprehensive chromosomal screening
      can be used to identify candidates for single embryo transfer. METHODS:
      Blastocysts from 437 patients underwent trophectoderm biopsy followed by array
      comparative genomic hybridization. Embryos were then selected for single or
      double embryo transfer. The number of euploid blastocysts produced and
      transferred for each patient was recorded, as was clinical pregnancy rate and
      multiple gestation rate. RESULTS: In patients with <= 3 euploid blastocysts,
      clinical pregnancy rate was higher in double, compared to single embryo
      transfers. However, in patients with >= 4 euploid blastocysts, clinical pregnancy
      rate was not reduced with single embryo transfer was performed, whereas the
      multiple gestation rate was greatly reduced. CONCLUSIONS: Size of the euploid
      embryo cohort is a marker for success in single embryo transfer cycles. Patients
      who produce at least four euploid blastocysts are outstanding candidates for
      single embryo transer.

PMID- 24659021
TI  - No clinically significant drug interactions between lenalidomide  and P
      glycoprotein substrates and inhibitors: results  from controlled phase I studies
      in healthy volunteers.
AB  - PURPOSE: Lenalidomide, a weak substrate of P-glycoprotein (P-gp) in vitro, is an
      oral anticancer drug eliminated predominantly via renal excretion as unchanged
      compound. The role of P-gp in lenalidomide disposition and the associated
      clinical relevance were evaluated. METHODS: Two phase I, crossover studies were
      conducted in healthy volunteers. In Study 1, subjects received lenalidomide (10
      mg * 7 days) alone or with the P-gp substrate digoxin (0.5 mg on Day 5). In Study
      2, subjects received lenalidomide (a single 25 mg dose) alone, the P-gp inhibitor
      quinidine (300-600 mg twice-daily * 5 days) plus lenalidomide (on Day 4), the P
      gp inhibitor/substrate temsirolimus (a single 25 mg dose) alone, or lenalidomide
      plus temsirolimus. Pharmacokinetic and safety data were collected for
      lenalidomide and the co-administrated drugs. RESULTS: There were no significant
      changes in the maximum concentration (C max) and area under the plasma
      concentration-time curve (AUC) of lenalidomide when co-administered with
      quinidine, digoxin, or temsirolimus. Neither the rate nor the capacity of
      lenalidomide renal excretion was affected by quinidine or temsirolimus, in
      addition lenalidomide absorption rate and bioavailability remained unchanged.
      Furthermore, lenalidomide had no significant effect on blood C max and AUC of
      temsirolimus and its active metabolite sirolimus (also a P-gp
      inhibitor/substrate). The C max of digoxin was slightly higher (+14 %) when
      administered with lenalidomide versus placebo. There were no other changes in
      digoxin pharmacokinetics upon co-administration with lenalidomide. No remarkable
      safety findings were observed. CONCLUSIONS: There are no clinically significant
      pharmacokinetic interactions between lenalidomide and substrates or inhibitors of
      P-gp.

PMID- 24659022
TI  - Effects of nicotine deprivation and replacement on BOLD-fMRI response to smoking
      cues as a function of DRD4 VNTR genotype.
AB  - INTRODUCTION: Reactivity to smoking cues is an important factor in the motivation
      to smoke and has been associated with the dopamine receptor 4 variable number
      tandem repeat (DRD4 exon III VNTR) polymorphism. However, little is known about
      the associated neural mechanisms. METHODS: Non-treatment-seeking Caucasian
      smokers completed overnight abstinence and viewed smoking and neutral cues during
      2 separate functional magnetic resonance imaging scans while wearing either a
      nicotine or placebo patch (order randomized) and were genotyped for the DRD4
      VNTR. We conducted mixed-effects repeated-measures analyses of variance (within
      subject factor: nicotine or placebo patch; between-subject factor: DRD4 long [L:
      >= 1 copy of >= 7 repeats] or short [S: 2 copies <= 6 repeats] genotype) of 6 a
      priori regions of interest. RESULTS: Relative to neutral cues, smoking cues
      elicited greater activity in bilateral ventral striatum and left amygdala during
      nicotine replacement and deactivation in these regions during nicotine
      deprivation. A patch * DRD4 interaction was observed in the left amygdala, an
      area associated with appetitive reinforcement and relapse risk, such that S
      allele carriers demonstrated greater activation on active patch than on placebo
      patch. CONCLUSIONS: Brain systems associated with reward salience may become
      primed and overreactive at nicotine replacement doses intended for the first step
      of smoking cessation and may become inhibited during nicotine withdrawal in DRD4
      S but not in DRD4 L carriers. These findings are consistent with the role of
      these regions in drug reinforcement and suggest a differential influence of
      nicotine replacement on amygdala activation in the association of incentive
      salience with smoking stimuli across DRD4 genotypes.

PMID- 24659023
TI  - alpha-Synuclein is prone to interaction with the GC-box-like sequence in vitro.
AB  - alpha-Synuclein (alpha-syn) is a presynaptic protein that is widely implicated in
      the pathophysiology of Parkinson's disease, a neurodegenerative disorder
      characterized by a progressive loss of dopaminergic neurons and the formation of
      Lewy bodies. Evidence suggests that alpha-syn could be imported into the nucleus
      and subsequently disrupt normal neuronal function. The existence of alpha-syn in
      the nucleus provides the possibility of interaction with DNA leading to gene
      transcript regulation. Thus, CD spectra were used to determine the specific DNA
      sequence with which alpha-syn is most likely to interact. Our results indicated
      that alpha-syn was prone to preferentially interact with the GC-box-like sequence
      in vitro at a ratio of 2:1 or less (alpha-syn: the GC-box-like sequence).

PMID- 24659025
TI  - Reply to commentary on: confusion in reporting pulmonary diffusion capacity for
      nitric oxide and the alveolar-capillary membrane conductance for nitric oxide.

PMID- 24659024
TI  - [Feasibility of balance training on mats in healthy,  moderately sportive women
      in old age. A pilot study].
AB  - PURPOSE: The aim of this pilot study was to assess the feasibility and the effect
      size of weekly group exercise sessions on an Airex(r) pad with an additional home
      program on the participants' balance. MATERIALS AND METHODS: Two training
      sessions (once a week in-group and once a week as a home program) were
      administered for 4 weeks. The intervention group (IG) trained on Airex(r) pads
      and the control group (CG) without the pad. This study examined the feasibility
      in terms of recruitment and randomization process, and compliance. Moreover, the
      effects were evaluated for static, dynamic, and functional balance. RESULTS: A
      total of 11 healthy women were recruited, and 10 women completed the 4-week
      training program (one drop-out was recorded). Of a total of 88 training sessions,
      82 were completed. The IG showed a significant difference for one test of dynamic
      balance. CONCLUSION: This pilot study was feasible. However, changes regarding
      recruitment and compliance should be made for future studies. Sensitive measuring
      instruments must be used for the evaluation of balance changes.

PMID- 24659027
TI  - Investigation on the enantioseparation of duloxetine by capillary
      electrophoresis, NMR, and mass spectrometry.
AB  - The enantiomeric separation of the antidepressant drug duloxetine was
      investigated by CE using 15 neutral CDs as chiral selectors. Among them, (2
      hydroxypropyl)-beta-CD and methyl-gamma-CD gave rise to the highest
      enantioresolution. The enantiomer migration order for duloxetine was found to be
      reversed depending on the CD employed: R-duloxetine was the first-migrating
      enantiomer for (2-hydroxypropyl)-beta-CD while it was the second-migrating
      enantiomer for methyl-gamma-CD. NMR and MS experiments were performed in order to
      justify this behavior. Although the elucidation of the structure of the
      enantiomer-CD complexes was not possible, their averaged stoichiometry was
      studied and their apparent and averaged equilibrium constants were calculated.
      The results obtained showed that the chiral separation of duloxetine by CE
      depends not only on the thermodynamic stability of the enantiomer-chiral selector
      complexes but also on their electrophoretic mobility. 

PMID- 24659026
TI  - Elevated cholesteryl ester transfer protein (CETP) activity, a major determinant
      of the atherogenic dyslipidemia, and atherosclerotic cardiovascular disease in
      South Asians.
AB  - AIMS: Why South Asians are at increased risk of premature atherosclerotic
      cardiovascular diseases compared with other ethnic groups is not fully
      understood. Atherogenic dyslipoproteinemia - hypertriglyceridemia, elevated
      numbers of low-density lipoprotein (LDL) particles and low high-density
      lipoprotein cholesterol (HDL-C) - is more common in South Asians but the
      mechanisms responsible have not been explicated. Here we examined whether the
      circulating lipid transfer protein, cholesteryl ester transfer protein (CETP),
      plays a role in the pathogenesis of the atherogenic dyslipoproteinemia among
      South Asians. METHODS AND RESULTS: CETP activity was determined by exogenous
      substrate assay in the serum of healthy, metabolically well-characterized
      individuals of South Asian and European descent (N = 244 and 238, respectively).
      Serum and lipoprotein lipids and apolipoproteins were measured and lipoprotein
      particle number and size were quantified via nuclear magnetic resonance
      spectroscopy. All the elements of the atherogenic dyslipoproteinemia were more
      severe in South Asians and CETP activity was significantly greater by 30% in
      South Asians compared with Europeans, adjusted for age, sex, body mass index and
      waist circumference (p < 0.0001). CETP activity was directly associated with
      serum triglycerides and inversely with HDL-C in the whole population. CETP
      activity was also directly related to apoB and LDL particle number. Finally,
      increased CETP activity was associated with pro-atherogenic reductions in HDL and
      LDL particle size. CONCLUSIONS: We identified novel associations between elevated
      CETP activity and the triad of quantitative and qualitative lipoprotein
      abnormalities in the atherogenic dyslipidemia in South Asians, a major
      contributor of increased atherosclerotic cardiovascular diseases in South Asians.

PMID- 24659028
TI  - Changes in mutational status during third-line treatment for metastatic
      colorectal cancer--results of consecutive measurement of cell free DNA, KRAS and
      BRAF in the plasma.
AB  - KRAS and BRAF mutations are responsible for primary resistance to epidermal
      growth factor receptor (EGFR) MoAbs in metastatic colorectal cancer (mCRC), but
      it is unknown what causes wildtype (wt) patients to develop resistance during
      treatment. We measured circulating free DNA (cfDNA), KRAS and BRAF in plasma and
      report the changes during third line treatment with cetuximab and irinotecan. One
      hundred-and-eight patients received irinotecan 350 mg/m2 q3w and weekly cetuximab
      (250 mg/m2) until progression (RECIST) or unacceptable toxicity. cfDNA and number
      of mutated KRAS/BRAF alleles in plasma at baseline and before each cycle was
      analyzed by an in-house qPCR. cfDNA and pKRAS levels decreased from baseline to
      cycle three and increased at time of progression (p = 0.008). The decrease was
      larger in responding patients than in non-responding (p < 0.05). Two patients
      with primary mutant disease had different types of mutations detected in the
      plasma, including synchronous KRAS and BRAF. Twelve patients had a primary KRAS
      mutant tumor, but wild-type disease according to baseline plasma analysis, eight
      of these obtained stabilization of disease. In five patients with primary wt
      disease a mutation appeared in plasma before radiological evidence of
      progression. Loss of mutations may explain observed benefit of treatment in
      primary mutant disease, whereas appearance of mutations during therapy may be
      responsible for acquired resistance in primary wt disease. Benefit from EGFR
      MoAbs may be influenced by the quantitative level of mutational alleles rather
      than by mutational status alone, and plasma levels of cfDNA, KRAS and BRAF could
      be used to monitor patients during treatment.

PMID- 24659029
TI  - A new Eu(3+)-labeled method for anticardiolipin antibody IgM.
AB  - BACKGROUND: The anticardiolipin antibodies (aCL) test has become a laboratory
      standard for the clinical diagnosis of antiphospholipid syndrome (APS). To better
      the quantitative detection of aCL-IgM so as to classify patients correctly and
      timely as APS positive, we established herein a new immunoassay based on a time
      resolved fluoroimmunoassay (TRFIA). METHODS: The complex of cardiolipin plus
      bovine anti-beta2 glycoprotein-I was used as antigen fixed on microtiter plates
      to detect serum aCL-IgM, and Eu(3+) -labeled rabbit antihuman IgM was used as
      conjugate. The precision, sensitivity, specificity, coefficient of recovery, and
      stability of the assay were evaluated, and comparison with the traditional,
      classical enzyme-linked immunosorbent assay (ELISA) was also made. RESULTS: The
      detection limit of the aCL-IgM TRFIA kit we established was 0.1 MPL U/ml, with a
      wider detectable range than commercial ELISA ones when a strong-positive specimen
      was diluted from 2,630.9 to 0.08 MPL U/ml. There was a good liner range within
      0.16 to 2,630.9 MPL U/ml, whereas it was within 5.14 to 328.86 MPL U/ml when
      using three commercial ELISA ones. The average intra- and interassay variability
      was 3.19 and 3.70%, respectively. The mean recovery rate was 101.95%. The
      clinical diagnostic specificity was 98%. Additionally, the established assay kit
      presented good characteristics of stability and correlated well with the ELISA,
      and the correlation coefficient was 0.955. CONCLUSION: The aCL-IgM TRFIA provides
      an approach to a more sensitive and reliable diagnosis of APS. Further validation
      of its use is required.

PMID- 24659030
TI  - Highly pathogenic H7N7 avian influenza in Italy.

PMID- 24659031
TI  - Antimicrobial susceptibility of Brachyspira hyodysenteriae determined by a broth
      microdilution method.

PMID- 24659032
TI  - TroX: a new method to learn about the genesis of aneuploidy from trisomic
      products of conception.
AB  - MOTIVATION: An estimated 10-30% of clinically recognized conceptions are
      aneuploid, leading to spontaneous miscarriages, in vitro fertilization failures
      and, when viable, severe developmental disabilities. With the ongoing reduction
      in the cost of genotyping and DNA sequencing, the use of high-density single
      nucleotide polymorphism (SNP) markers for clinical diagnosis of aneuploidy and
      biomedical research into its causes is becoming common practice. A reliable,
      flexible and computationally feasible method for inferring the sources of
      aneuploidy is thus crucial. RESULTS: We propose a new method, TroX, for analyzing
      human trisomy data using high density SNP markers from a trisomic individual or
      product of conception and one parent. Using a hidden Markov model, we infer the
      stage of the meiotic error (I or II) and the individual in which non-disjunction
      event occurred, as well as the crossover locations on the trisomic chromosome. A
      novel and important feature of the method is its reliance on data from the
      proband and only one parent, reducing the experimental cost by a third and
      enabling a larger set of data to be used. We evaluate our method by applying it
      to simulated trio data as well as to genotype data for 282 trios that include a
      child trisomic for chromosome 21. The analyses show the method to be highly
      reliable even when data from only one parent are available. With the increasing
      availability of DNA samples from mother and fetus, application of approaches such
      as ours should yield unprecedented insights into the genetic risk factors for
      aneuploidy. AVAILABILITY AND IMPLEMENTATION: An R package implementing TroX is
      available for download at http://przeworski.uchicago.edu/.

PMID- 24659033
TI  - Atrial flutter demonstrated by M-mode echocardiography.
AB  - This report and images describe a case of atrial flutter with 2:1 conduction
      pattern in a 3 year-old male with d-TGA, ASD, and VSD status-post repair, which
      was demonstrated by M-mode echocardiography.

PMID- 24659040
TI  - Inappropriate prescribing in patients accessing specialist  palliative day care
      services.
AB  - BACKGROUND: For patients accessing specialist palliative care day services,
      medication is prescribed routinely to manage acute symptoms, treat long-term
      conditions or prevent adverse events associated with these conditions. As such,
      the pharmacotherapeutic burden for these patients is high and polypharmacy is
      common. Consequently, the risk of these patients developing drug-related
      toxicities through drug-drug interactions is exacerbated. Medication use in this
      group should, therefore, be evaluated regularly to align with achievable
      therapeutic outcomes considering remaining life expectancy. OBJECTIVE: To (1)
      assess the prevalence of inappropriate medication use; (2) identify potential
      drug-drug interactions; and, (3) determine how many potential drug- drug
      interactions could be prevented by discontinuing inappropriate medication.
      SETTING: A specialist tertiary care palliative care centre in Northern England
      serving a population of 330,000. MAIN OUTCOME MEASURE: Prescribing of
      inappropriate medication. METHOD: Medication histories for patients accessing a
      specialist palliative day care centre were established and a modified Delphi
      method was used to reach consensus of medication appropriateness. The Delphi
      method utilized a framework considering the following factors: remaining life
      expectancy of the patient, time until benefit of the treatment, goals of care and
      treatment targets. Potential drug interactions were established using drug
      interaction recognition software and categorised by their ability to cause harm.
      RESULTS: A total number of 132 patients were assessed during the study period who
      were prescribed 1,532 (mean = 12/patient) medications; 238 (16 %) were considered
      inappropriate in the context of limited life expectancy. The most common class of
      medications considered inappropriate were the statins, observed in 35 (27 %)
      patients. A total of 267 potential drug-drug interactions were identified; 112
      were clinically significant and 155 were not considered clinically significant.
      Discontinuation of inappropriate medication would reduce the total number of
      medications taken to 1,294 (mean = 10/patient) and prevent 31 clinically
      significant potential drug-drug interactions. CONCLUSION: Patients accessing
      specialist palliative day care services take many inappropriate medications.
      These medications not only increase the pharmacotherapeutic burden for the
      patient but they also contribute to potential drug-drug interactions. These
      patients should have their medication reviewed in the context of life limiting
      illness aligned with achievable therapeutic outcomes.

PMID- 24659041
TI  - Negative cognitions as a moderator in the relationship between PTSD and substance
      use in a psychiatrically hospitalized adolescent sample.
AB  - Adolescents exposed to trauma are more likely to engage in alcohol and marijuana
      use compared to their nontrauma-exposed counterparts; however, little is known
      about factors that may moderate these associations. This study examined the
      potential moderating effect of cognitions relevant to exposure to trauma (i.e.,
      negative view of self, world, and future) in the association between
      posttraumatic stress disorder (PTSD) diagnosis and substance use among a
      psychiatric inpatient sample of 188 adolescents. Findings were that PTSD
      diagnosis was not significantly associated with substance-use diagnoses, but was
      associated with substance-use symptoms, accounting for 2.9% and 9.6% of the
      variance in alcohol and marijuana symptoms, respectively. The association between
      PTSD diagnosis and substance use symptoms, however, was moderated by negative
      cognitions, with PTSD and high negative cognitions (but not low negative
      cognitions) being significantly positively associated with substance use
      symptoms. The relevant cognitions differed for alcohol symptoms and marijuana
      symptoms. Children and adolescents who experience trauma and PTSD may benefit
      from early interventions that focus on cognitive processes as one potential
      moderator in the development of posttrauma substance use. 

PMID- 24659042
TI  - Compressive fatigue properties of a commercially available acrylic bone cement
      for vertebroplasty.
AB  - Acrylic bone cements are widely used for fixation of joint prostheses as well as
      for vertebral body augmentation procedures of vertebroplasty and balloon
      kyphoplasty, with the cement zone(s) being subjected to repeated mechanical
      loading in each of these applications. Although, in vertebroplasty and balloon
      kyphoplasty, the cement zone is exposed to mainly cyclical compressive load, the
      compressive fatigue properties of acrylic bone cements used in these procedures
      are yet to be determined. The purposes of the present study were to determine the
      compressive fatigue properties of a commercially available cement brand used in
      vertebroplasty, including the effect of frequency on these properties; to
      identify the cement failure modes under compressive cyclical load; and to
      introduce a screening method that may be used to shorten the lengthy character of
      the standardized fatigue tests. Osteopal[Formula: see text] was used as the model
      cement in this study. The combinations of maximum stress and frequency used were
      50.0, 55.0, 60.0, 62.5 and 75.5 MPa at 2 Hz; and of 40.0, 55.0, 60.0, 62.5 or
      75.5 MPa at 10 Hz. Through analysis of nominal strain-number of loading cycles
      results, three cement failure modes were identified. The estimated mean fatigue
      limit at 2 Hz (55.4 MPa) was significantly higher than that at 10 Hz (41.1 MPa).
      The estimated fatigue limit at 2 Hz is much higher than stresses commonly found
      in the spine and also higher than that for other acrylic bone cements tested in a
      full tension-compression fatigue test, which indicates that tension-compression
      fatigue testing may substantially underestimate the performance of cements
      intended for vertebroplasty. A screening method was introduced which may be used
      to shorten the time spent in performing compressive fatigue tests on specimens of
      acrylic bone cement for use in vertebral body augmentation procedures. 

PMID- 24659043
TI  - Setting up a probe based, closed tube real-time PCR assay for focused detection
      of variable sequence alterations.
AB  - During diagnostic workflow when detecting sequence alterations, sometimes it is
      important to design an algorithm that includes screening and direct tests in
      combination. Normally the use of direct test, which is mainly sequencing, is
      limited. There is an increased need for effective screening tests, with "closed
      tube" during the whole process and therefore decreasing the risk of PCR product
      contamination. The aim of this study was to design such a closed tube, detection
      probe based screening assay to detect different kind of sequence alterations in
      the exon 11 of the human c-kit gene region. Inside this region there are variable
      possible deletions and single nucleotide changes. During assay setup, more probe
      chemistry formats were screened and tested. After some optimization steps the
      taqman probe format was selected.

PMID- 24659044
TI  - Utility of immunohistochemical markers in diagnosis of follicular cell derived
      thyroid lesions.
AB  - Differentiating the follicular derived lesions can be challenging. Although
      immunohistochemistry is generally accepted as a useful ancillary technique in the
      diagnosis, controversy exists regarding the best marker or combination of markers
      to distinguish each lesion from its mimics. In this study, we aimed at evaluating
      multiple markers to compare their sensitivity and usefulness, and to find out if
      a combination of the evaluated markers can be of additional value in
      discriminating thyroid lesions. The study included two groups of follicular
      derived thyroid lesions; benign group (Grave's disease, nodular goiter,
      Hashimoto's and adenoma) and malignant group (papillary, follicular carcinoma,
      well differentiated tumors of unknown malignant potential and follicular tumour
      of unknown malignant potential). Immunohistochemical evaluation of CD56, HBME-1,
      Gaectin-3 and CK19 were done. The sensitivity, specificity for each marker and
      their combination were calculated. Each marker was sensitive and specific for
      certain lesion but the sensitivity and specificity was increased when use
      combination of markers. Although no single marker is completely sensitive and
      specific for follicular thyroid lesions, the combination of CD56, HBME-1, Gaectin
      3 and CK19 attains high sensitivity and specificity in diagnosis.

PMID- 24659045
TI  - Zinc oxide nanoparticles modulates the production of beta-glucosidase and
      protects its functional state under alcoholic condition in Saccharomyces
      cerevisiae.
AB  - In the present investigation, we have investigated the effect of zinc oxide
      nanoparticles (ZnONP) on the production of beta-glucosidase (BGL) in
      Saccharomyces cerevisiae under various conditions. ZnONP was synthesized
      chemically and characterized using various standard techniques. The results
      revealed that yeast culture administered with 5 mM ZnONP enhanced the
      intracellular BGL activity up to 28 % compared to control with simultaneous
      growth of cells. However, at a higher dose of ZnONP (10 and 15 mM), both the
      activity of the enzyme and yeast growth was dropped. When yeast cells were grown
      in alcoholic medium (2, 5, and 10 % ethanol), the growth was found inhibited with
      substantial reduction of intracellular BGL activity. Interestingly, the
      administration of ZnONP further inhibited the cell growth, however, suppressed
      the alcoholic effect on enzyme activity. Moreover, under the same condition,
      ZnONP enhanced the biological activity of the enzyme in cells, indicated a higher
      yield of BGL production. When the mechanism of ZnONP-mediated cell growth
      inhibition was investigated, N-acetylcysteine (NAC)-based cell growth study
      proved that reactive oxygen species (ROS) was not the sole cell death mechanism
      induced by ZnONP, indicating a second mechanism of cell death. Our findings
      provide a new insight on the potential application of ZnONP as an external
      supplement to enhance the active production of BGL like important industrial
      enzyme in S. cerevisiae in both normal and alcohol stressed condition as well as
      to produce baker's yeast in higher amount.

PMID- 24659046
TI  - Vacuum stripping of ethanol during high solids fermentation of corn.
AB  - In corn-ethanol industry, yeast stress inducing glucose concentrations produced
      during liquefaction and subsequent high ethanol concentrations produced during
      fermentation restrict slurry solids to 32 % w/w. These limits were circumvented
      by combining two novel technologies: (1) granular starch hydrolyzing enzyme
      (GSHE) to break down starch simultaneously with fermentation and (2) vacuum
      stripping to remove ethanol. A vacuum stripping system was constructed and
      applied to fermentations at 30, 40, and 45 % solids. As solids increased from 30
      to 40 %, ethanol yield decreased from 0.35 to 0.29 L/kg. Ethanol yield from 45 %
      solids was only 0.18 L/kg. An improvement was conducted by increasing enzyme dose
      from 0.25 to 0.75 g/g corn and reducing yeast inoculum by half. After
      improvement, ethanol yield from 40 % solids vacuum treatment increased to 0.36
      L/kg, comparable to ethanol yield from 30 % solids (control).

PMID- 24659047
TI  - Direct conversion of pretreated straw cellulose into citric acid by co-cultures
      of Yarrowia lipolytica SWJ-1b and immobilized Trichoderma reesei mycelium.
AB  - The immobilized cellulase-producing mycelium of Trichoderma reesei was found to
      produce 2.9 U/ml of cellulase activity within 144 h while 2.1 U/ml of cellulase
      activity was produced within 120 h by the free mycelium of the same strain. When
      the immobilized mycelium of T. reesei was co-cultivated with the free cells of
      Yarrowia lipolytica SWJ-1b in flask, Y. lipolytica SWJ-1b could yield 10.7 g/l of
      citric acid and 3.9 g/l of isocitric acid from 40.0 g/l pretreated straw within
      240 h. Under the similar conditions, Y. lipolytica SWJ-1b could yield 32.8 g/l of
      citric acid and 4.7 g/l of isocitric acid from 40.0 g/l pretreated straw
      supplemented with 20.0 g/l glucose within 288 h. When the co-cultures were grown
      in 10-l fermentor, Y. lipolytica SWJ-1b could yield 83.4 g/l of citric acid and
      8.7 g/l of isocitric acid from 100.0 g/l of pretreated straw supplemented with
      50.0 g/l glucose within 312 h.

PMID- 24659048
TI  - Cloning of LicB from Clostridium thermocellum and its efficient secretive
      expression of thermostable beta-1,3-1,4-glucanase.
AB  - beta-1,3-1,4-glucanase is a widely used enzyme in brewing and in animal feed
      processing. To produce the bacterial enzyme at an industrial scale, the enzyme
      should be able to be secreted from microbial cells into fermentation broth and be
      stable in different conditions. In this study, the LicB gene encoding beta-1,3
      1,4-glucanase (lichenase) from Clostridium thermocellum was secretively expressed
      in a secretive strain, Bacillus subtilis WB800, with eight extracellular protease
      deletion which made LicB expressed obviously and reached 1.18 U/g cell mass. The
      secreted beta-1,3-1,4-glucanase was found to be active from 40  degrees C to 80 
      degrees C and achieved the optimal activity at 80  degrees C. The enzyme also has
      a wide pH range (pH 4-11). The most common metal ions and chemicals were found to
      be inert on its activity. The property of LicB-encoded beta-1,3-1,4-glucanase and
      its efficient secretive expression makes it a potential enzyme for industrial
      production and application.

PMID- 24659049
TI  - Optional stopping: no problem for Bayesians.
AB  - Optional stopping refers to the practice of peeking at data and then, based on
      the results, deciding whether or not to continue an experiment. In the context of
      ordinary significance-testing analysis, optional stopping is discouraged, because
      it necessarily leads to increased type I error rates over nominal values. This
      article addresses whether optional stopping is problematic for Bayesian inference
      with Bayes factors. Statisticians who developed Bayesian methods thought not, but
      this wisdom has been challenged by recent simulation results of Yu, Sprenger,
      Thomas, and Dougherty (2013) and Sanborn and Hills (2013). In this article, I
      show through simulation that the interpretation of Bayesian quantities does not
      depend on the stopping rule. Researchers using Bayesian methods may employ
      optional stopping in their own research and may provide Bayesian analysis of
      secondary data regardless of the employed stopping rule. I emphasize here the
      proper interpretation of Bayesian quantities as measures of subjective belief on
      theoretical positions, the difference between frequentist and Bayesian
      interpretations, and the difficulty of using frequentist intuition to
      conceptualize the Bayesian approach.

PMID- 24659050
TI  - Feeling of knowing and restudy choices.
AB  - Feeling-of-knowing judgments (FOK-Js) reflect people's confidence that they would
      be able to recognize a currently unrecallable item. Although much research has
      been devoted to the factors determining the magnitude and accuracy of FOK-Js,
      much less work has addressed the issue of whether FOK-Js are related to any form
      of metacognitive control over memory processes. In the present study, we tested
      the hypothesis that FOK-Js are related to participants' choices of which
      unrecallable items should be restudied. In three experiments, we showed that
      participants tend to choose for restudy items with high FOK-Js, both when they
      are explicitly asked to choose for restudy items that can be mastered in the
      restudy session (Exps. 1a and 2) and when such specific instructions are omitted
      (Exp. 1b). The study further demonstrated that increasing FOK-Js via priming cues
      affects restudy choices, even though it does not affect recall directly. Finally,
      Experiment 2 showed the strategy of restudying unrecalled items with high FOK-Js
      to be adaptive, because the efficacy of restudy is greater for these items than
      for items with low FOK-Js. Altogether, the present findings underscore an
      important role of FOK-Js for the metacognitive control of study operations.

PMID- 24659053
TI  - Capillary electrokinetic fractionation mass spectrometry (CEkF/MS): technology
      setup and application to metabolite fractionation from complex samples coupled at
      line with ultrahigh-resolution mass spectrometry.
AB  - Capillary electrokinetic fractionation (CEkF) is investigated as a new, simple,
      and robust approach for semipreparative and analytical sample analysis based on
      pKa -dependant pH-driven electrophoretic mobility. CEkF was optimized with
      contactless conductivity detection and conducted with 10 kV reverse voltage for
      10 min, then coupled on/at-line to ESI/MS. We propose a semi-empirical model with
      14 representative compounds based on the correlation between sample/medium pH
      regulating the partial charge, the electrokinetic loading of the capillary and
      intensity (I) of analytes. According to the model, an empirical function (I = f
      (pH)) could be derived to calculate the acid dissociation constant (pKa ) of
      various model compounds based on their pH-dependant MS intensity profiles with
      the RSD < 4.05. Using the ultrahigh-resolution of ion cyclotron resonance Fourier
      transform MS, the pKa model was further illustrated in real samples into the
      structure prediction of important compounds in wine over two vintages. The
      established CEkF was successfully used to selectively fractionate sulfur
      compounds from the complex wine samples at pH 1.66. The proposed CEkF approach
      should allow in the future the simultaneous pKa evaluation of multiple
      constituents without complicated separation out of a complex mixture in
      metabolomics or environmental chemistry.

PMID- 24659051
TI  - Unraveling the signal scenario of fruit set.
AB  - Long-term goals to impact or modify fruit quality and yield have been the target
      of researchers for many years. Different approaches such as traditional
      breeding,mutation breeding, and transgenic approaches have revealed a regulatory
      network where several hormones concur in a complex way to regulate fruit set and
      development,and these networks are shared in some way among species with
      different kinds of fruits. Understanding the molecular and biochemical networks
      of fruit set and development could be very useful for breeders to meet the
      current and future challenges of agricultural problems.

PMID- 24659052
TI  - Functional conservation and divergence of J-domain-containing ZUO1/ZRF orthologs
      throughout evolution.
AB  - Heat shock protein 40s (Hsp40s), also known as J-proteins, are conserved in
      prokaryotes and eukaryotes. The Zuotin/Zuotin-related factor (ZUO1/ZRF) family
      belongs to a novel Hsp40 clade exclusively found in eukaryotes. Zuotin/Zuotin
      related factor proteins are characterized by a large N terminal ZUO1 domain
      originally identified in the yeast ZUO1 protein. The ZUO1 domain is characterized
      by a highly conserved J-domain, together with an atypical UBD domain first
      identified in the human ZRF1 protein. Furthermore, ZUO1/ZRF protein families in
      animals and plants harbor a pair of C terminal SANT domains, suggesting the
      divergence of their functions with those in fungi. Zuotin/Zuotin-related factor
      proteins retain the ancestral function as an Hsp70co-chaperone implicated in
      protein folding and renaturation after stress; these proteins also perform
      diverse neofunctions in the cytoplasm and transcriptional and/or epigenetic
      regulatory functions in the nucleus. Therefore, these proteins are involved in
      translational fidelity control, ribosomal biogenesis, asymmetric cell division,
      cell cycle, apoptosis, differentiation, and tumorigenesis. The results of
      sequence and domain organization analysis of proteins from diverse organisms
      provided valuable insights into the evolutionary conservation and diversity of
      ZUO1/ZRF protein family. Further, phylogenetic analysis provides a platform for
      future functional investigation on the ZUO1/ZRF protein family, particularly in
      higher plants.

PMID- 24659054
TI  - Metabolomics biomarkers of frailty in elderly breast cancer patients.
AB  - Metabolome analysis has emerged as a powerful technique for detecting and define
      specific physio-pathological phenotypes. In this investigation the diagnostic
      potential of metabolomics has been applied to better characterize the multiple
      biochemical alterations that concur in the definition of the frailty phenotype
      observed in elderly breast cancer patients. The study included 89 women with
      breast cancer (range 70-97 years) classified as Fit (n = 49), Unfit (n = 23), or
      Frail (n = 17) according to comprehensive geriatric assessment. The serum
      metabolomic profile was performed by tandem mass spectrometry and included
      different classes of metabolites such as amino acids, acylcarnitines, sphingo-,
      and glycerol-phospolipids. ANOVA was applied to identify the metabolites
      differing significantly among Fit, Unfit, and Frail patients. In patients
      carrying the frail phenotype, the amino acid perturbations involve serine,
      tryptophan, hydroxyproline, histidine, its derivate 3-methyl-hystidine, cystine,
      and beta-aminoisobutyric acid. With regard to lipid metabolism, the frailty
      phenotype was characterized by a decrease of a wide number of glycerol- and
      sphingo-phospholipid metabolites. These metabolomics biomarkers may give a
      further insight into the biochemical processes involved in the development of
      frailty in breast cancer patients. Moreover, they might be useful to refine the
      comprehensive geriatric assessment model.

PMID- 24659059
TI  - Contained aortic annulus rupture with persisting false aneurysm after
      transfemoral transcatheter aortic valve implantation.
AB  - With older age and increasing comorbidities, conventional operative procedures
      for severe symptomatic aortic stenosis are associated with a high surgical risk.
      To date, transfemoral transcatheter aortic valve implantation (TF-TAVI)
      represents an accepted alternative method of intervention with a cardiovascular
      and all-cause mortality similar to operative replacement at early and long-term
      follow-up in this high risk population (Thomas et al., Circulation 124:425-433,
      2011). Despite growing experience of the operators and improvement of the devices
      procedural and perioperative complications still occur (Panchal et al., Am J
      Cardiol, 2013). Aortic annulus rupture as well as the rupture of the membranous
      ventricular septum has been reported (Aminian et al., Catheter Cardiovasc Interv
      81:E72-E75, 2013). We present the unusual case of an 80-year-old female who
      developed a false aneurysm following a contained aortic annulus rupture during a
      TF-TAVI procedure.

PMID- 24659063
TI  - Operative complications during pregnancy after gastric bypass--a register-based
      cohort study.
AB  - BACKGROUND: Late complications to bariatric surgery during pregnancy have become
      an area of concern. Expansion of the uterus and the following displacement of the
      small intestine may increase the risk of internal herniation. We wanted to
      estimate the risk and consequences of surgical complications during pregnancy in
      a national cohort of women with a history of gastric bypass surgery. METHODS: A
      national, register-based cohort study of all Danish women with a history of
      gastric bypass surgery who had given birth from 2004 to 2010 was conducted.
      Surgical codes registered during pregnancy and until 120 days postpartum were
      identified in national registers, and the individual charts were reviewed in
      relevant cases. RESULTS: Of 286 women giving birth, fourteen women underwent
      procedures that might be related to the earlier gastric bypass surgery. Three
      women were operated on suspicion of internal herniation. In all three cases,
      mesenteric defects were found, and herniation was still present in two women, one
      of which died postoperatively. Five women were investigated by gastroscopy or
      sigmoidoscopy either during or after the delivery, and in six women
      cholecystectomy was performed during the puerperium. CONCLUSIONS: The incidence
      of internal herniation during pregnancy was 1 % in our study. Internal herniation
      may be a serious complication in pregnant women, and both the diagnosis and
      treatment requires handling by experienced obstetrical, radiological, and
      surgical staff.

PMID- 24659060
TI  - Listening to the voices of native Hawaiian elders and 'ohana caregivers:
      discussions on aging, health, and care preferences.
AB  - Native Hawaiians, the indigenous people of Hawai'i, are affected by varying
      social and health disparities that result in high prevalence of chronic disease,
      early onset of disability, and shorter life expectancy compared to other ethnic
      groups in Hawai'i. Six listening meetings were conducted, involving 41 community
      dwelling kupuna (Native Hawaiian elders) and 'ohana (family) caregivers to
      investigate health and care preferences that offer the potential for improving
      well-being in later life for Native Hawaiian elders. As background, we provide
      three explanatory perspectives and theories-life course perspective, minority
      stress theory, and historical trauma-that guided the design of this study and
      provided the study's context. A number of overarching themes and subthemes were
      identified, some of which point to universal concerns with age and caregiving
      (such as challenges and costs associated with growing old and caregiving) and
      others that are culturally specific (such as influence of culture and social
      stressors, including discrimination, on health needs and care preferences).
      Results give further support to the urgency of affordable, accessible, and
      acceptable programs and policies that can respond to the growing health and care
      needs of native elders and family caregivers.

PMID- 24659064
TI  - The effect of vitamin A supplementation on disease progression, cytokine levels
      and gene expression in multiple sclerotic patients: study protocol for a
      randomized controlled trial.
AB  - Multiple Sclerosis (MS) is a chronic inflammatory disease that leads to
      degeneration of the brain and spinal tissue. Imbalances of CD4+ T cells including
      Thelper1 (Th1)/Thelper2 (Th2) and Thelper17 (Th17)/Tregulatory (Treg), their
      secreted cytokines and gene expressions, are important aspects of in
      immunopathogenesis of MS. Vitamin A and its metabolites can regulate the immune
      system and appears to be effective in preventing progression of the autoimmune
      disease such as MS. Disease progression was evaluated By Magnetic Resonance
      Imaging (MRI), Expanded Disability States Scale (EDSS) and Multiple Sclerosis
      Functional Composite (MSFC) tests. Cytokine levels were measured using ELISA kits
      and gene expression was quantified by Real time PCR (RT-PCR) system. According to
      the difference between the epidemiological and clinical data on the relationship
      between vitamin A and immune system regulation, this study of the first time
      assesses Immune function as well as gene expression and progression of the
      disease following administration of vitamin A supplement. 

PMID- 24659065
TI  - Protective effects of crocin against streptozotocin-induced oxidative damage in
      rat striatum.
AB  - The study aimed to investigate the protective effects of crocin (Cro) against
      streptozotocin (STZ)-induced oxidative damage in rat striatum. Animals were
      randomly divided into four groups (five each). Group 1 (sham) were treated with
      normal saline (2 ml/kg, p.o.). Group 2 (STZ-lesioned or lesion) were injected
      with ICV-STZ (3 mg/kg bilaterally, on day 1 and 3) and treated with normal saline
      (2 ml/kg, p.o.) respectively, for 21 days. Group 3 (sham+Cro) were injected ICV
      on day 1 and 3 with artificial CSF and treated with crocin (100 mg/kg, p.o.) for
      21 days. Group 4 (lesion+Cro) were injected with ICV STZ (3 mg/kg bilaterally, on
      day 1 and 3) and treated with crocin (100 mg/kg, p.o.) for 21 days. The
      homogenized striatum was used for measuring malondialdehyde (MDA), and total
      thiol contents besides glutathione peroxidase (GPx) activity. Crocin treatment
      resulted in a significant reduction in MDA concentration as compared to the STZ
      lesioned rats. Moreover, crocin produced a significant elevation in total thiol
      content and GPx activity, as compared with STZ-lesioned group. The present
      findings provide evidence that crocin may have a therapeutic significance for
      neurodegenerative diseases such as Alzheimer's disease (AD). 

PMID- 24659066
TI  - Evaluation of haptoglobin phenotypes in association with clinical features of
      patients suffered from preterm labor disease.
AB  - Preterm birth means the birth before thirty seven week of pregnancy that causes a
      lot of complications for the baby. Variety factors are suggested to be involved
      in disease. In this study, we decided to evaluate haptoglobin (Hp) phenotypes
      association with clinical features of patients suffered from premature delivery
      to understand better the possible correlation of genetic and clinical features in
      this disease. This cross-sectional analytic descriptive study has been carried
      out in two groups of 120 women, 60 with preterm and 60 with term labor. Patients
      were selected with previously diagnosed by gynecologist with preterm birth in the
      labor during the study period. After performing diagnostic tests, the frequency
      of each haptoglobin phenotype in the two groups was analyzed using the Chi-square
      test (X2) test and SPSS software. The maximum serum haptoglobin phenotype
      frequency in patients with Hp2-2, was 43 (71.7%) whereas in healthy individuals,
      35 (58.3%). No, statistically significant differences between the two groups were
      found (p=0.310). But based on some patients clinical features such as their
      history of preterm delivery, previous history of recurrent abortions and history
      of preterm delivery in their family, significant association was found with Hp2-2
      compared with healthy control (p<0.003). This study showed that Hp2-2 phenotypes
      levels in the case group was higher than in control but the factors influencing
      the presence or absence of preterm labor is clinically various. 

PMID- 24659067
TI  - Saccular function in otosclerosis patients: bone conducted-vestibular evoked
      myogenic potential analysis.
AB  - Vestibular involvements have long been observed in otosclerotic patients. Among
      vestibular structures saccule has the closest anatomical proximity to the
      sclerotic foci, so it is the most prone vestibular structure to be affected
      during the otosclerosis process. The aim of this study was to investigate the
      saccular function in patients suffering from otosclerosis, by means of Vestibular
      Evoked Myogenic Potential (VEMP). The material consisted of 30 otosclerosis
      patients and 20 control subjects. All participants underwent audiometric and VEMP
      testing. Analysis of tests results revealed that the mean values of Air-Conducted
      Pure Tone Average (AC-PTA) and Bone-Conducted Pure Tone Average (BC-PTA) in
      patients were 45.28 +/- 15.57 and 19.68 +/- 10.91, respectively and calculated 4
      frequencies Air Bone Gap (ABG) was 25.64 +/- 9.95. The VEMP response was absent
      in 14 (28.57%) otosclerotic ears. A statistically significant increase in latency
      of the p13 was found in the affected ears (P=0.004), differences in n23 latency
      did not reach a statistically significant level (P=0.112). Disparities in
      amplitude of p13-n23 in between two study groups was statistically meaningful
      (P=0.009), indicating that the patients with otosclerosis had lower amplitudes.
      This study tends to suggest that due to the direct biotoxic effect of the
      materials released from the otosclerosis foci on saccular receptors, there might
      be a possibility of vestibular dysfunction in otosclerotic patients. 

PMID- 24659068
TI  - Relationship between prooxidant-antioxidant balance and severity of coronary
      artery disease in patients of Imam Khomeini Hospital of Tehran, Iran.
AB  - The balance between reactive oxygen species production and antioxidant activity
      has an important role in oxidative stress associated diseases including coronary
      artery disease. In this study, the prooxidant-antioxidant balance (PAB) and its
      correlations with serum lipid levels, uric acid levels, and severity of coronary
      artery involvement were examined. The aim of this study was to determine the
      diagnostic value of PAB as a predictor in coronary artery disease (CAD). Seventy
      two patients and 68 healthy subjects were selected. PAB was determined using
      standard solutions and ELISA. Triglyceride, total cholesterol, LDL-cholesterol,
      HDL-cholesterol and uric acid levels were measured by enzymatic method. Mean PAB
      was 66.4 +/- 2.84 (HK units) in healthy people, 77.37 +/- 33.51 (HK units) in
      patients with one vessel CAD, 63.76 +/- 29.47 (HK units) in patients with two
      vessel CAD and 68.59 +/- 24.51 (HK units) in patients with three or more vessel
      CAD. There was no significant difference between PAB values in different severity
      groups (P=0.41). PAB significantly and indirectly correlated with uric acid level
      in two vessels CAD. The study shows that PAB can be a predictor of CAD associated
      with other risk factors, but not alone.

PMID- 24659069
TI  - Axillary nerve block in comparison with intravenous midazolam/fentanyl for
      painless reduction of upper extremity fractures.
AB  - The painful nature of fractures has made it inevitable to use various anesthetic
      techniques to reduce or immobilize fractured parts. In the present study,
      axillary nerve block was compared with intravenous midazolam/fentanyl to induce
      anesthesia for Painless Reduction of Upper Extremity Fractures. The subjects in
      the present clinical trial consisted of 60 patients with upper extremity
      fractures. They were randomly divided into two equal groups of intravenous
      sedation (IVS) with midazolam/fentanyl and axillary nerve block (ANB). Rate of
      anesthesia induction, recovery time, and pain intensities at baseline, during the
      procedure and at the end of the procedure were recorded in both groups. Data was
      analyzed and compared between the two groups with SPSS 18 statistical software
      using appropriate tests. Demographic data, vital signs and means of pain
      intensities at the beginning of the procedure were equal in the two groups. In
      the IVS group, the overall duration of the procedure was shorter with more rapid
      onset of anesthesia (P<0.05). In contrast, the recovery time was much shorter in
      the ANB group (P<0.001). No life or organ threatening complications were observed
      in the two groups. Axillary nerve block can be considered an appropriate
      substitute for intravenous sedation in painful procedures of the upper extremity.

PMID- 24659071
TI  - SWOT analysis in Sina Trauma and Surgery Research Center.
AB  - The present study was conducted with the aim of identifying and evaluating the
      internal and external factors, affecting the Sina Trauma and Surgery Research
      Center, affiliated to Tehran University of Medical Sciences and propose some of
      related strategies to senior managers. We used a combined quantitative and
      qualitative methodology. Our study population consisted of personnel (18
      individuals) at Sina Trauma and Surgery Research Center. Data-collection tools
      were the group discussions and the questionnaires. Data were analyzed with
      descriptive statistics and SWOT (Strength, Weakness, Opportunities and Threats)
      analysis. 18 individuals participated in sessions, consisting of 8 women (44.4%)
      and 10 men (55.6%). The final scores were 2.45 for internal factors (strength
      weakness) and 2.17 for external factors (opportunities-threats). In this study,
      we proposed 36 strategies (10 weakness-threat strategies, 10 weakness-opportunity
      strategies, 7 strength-threat strategies, and 9 strength-opportunity strategies).
      The current status of Sina Trauma and Surgery Research Center is threatened weak.
      We recommend the center to implement the proposed strategies.

PMID- 24659070
TI  - The Epworth Sleepiness Scale for screening of the drowsy driving: comparison with
      the maintenance of wakefulness test in an Iranian sample of commercial drivers.
AB  - Traffic fatalities are a major cause of morbidity and mortality in Iran.
      Occupational sleep medicine field needs more cost-effective and applicable tests
      for screening purposes. This study reports on a pilot screening study for drowsy
      drivers in an urban Iranian sample of commercial drivers. The Maintenance of
      Wakefulness Test (MWT) measures the ability to remain awake objectively. Sleep
      latency in MWT is a reasonable predictor of driving simulator performance in
      drivers. In this study, we evaluate whether the Epworth Sleepiness Scale (ESS)
      and MWT are equally useful in drivers with possible Excessive Daytime Sleepiness
      (EDS). 46 consecutive road truck drivers in a transportation terminal entered
      into this study. The ESS score of patients with normal and abnormal MWT was
      3.24+/-2.4 and 4.08+/-3 respectively which was not significantly differenced (P
      value = 0.34). No significant correlation was found between the ESS and sleep
      latency in MWT (r=-0.28, 95%CI= -0.58 to 0.02). By using the receiver operating
      characteristic analysis, the area under the curve was found to be 0.57 (95%
      confidence interval = 0.37- 0.77) which is not statistically acceptable (P
      value=0.46). Our finding showed that the MWT and ESS do not measure the same
      parameter. 

PMID- 24659072
TI  - Investigating the effect of clinical governess approach on patients' length of
      stay in emergency department: an action research study.
AB  - Over the past decade, clinical governance approach with aims to improve the
      quality of health services has been proposed in Iran. Considering the obvious
      problems especially patients' length of stay (LOS) in the emergency departments
      (EDs); the present study has been carried out with the purpose of Investigating
      the effect of clinical governess approach on patients' LOS in the one of the
      largest medical centers in the country. After the problem was specified by the 17
      interviews with employees and managers of the ED; the emergency clinical
      governance committee was formed by two academic researchers and seven ED staff
      (key participants) that had the most involvement with the subject of study. The
      activities of the committee, including planning, acting, observing and
      reflecting, was organized by using participatory action research approach and
      action research cycle (Kemmis 1995). During this time, three formal meetings with
      key participants were held in 6-month intervals. Monthly records of patients'
      average LOS and interview with ED staff were used to analyze the findings. The
      research was completed with two cycles in one year. Committee members took the
      following actions. As a result, the patients' LOS reduced from 2.68 days to 1.73
      days. Make regular patients visits by medical groups especially orthopedists and
      neurologists; Decision making about patients situation by emergency physicians
      and transferring patients to the relevant units by bed managers; Refusing to
      admit elective patients during overcrowding times; to regulate the list of
      patients requiring ICU by anesthesiologists. Prolonged LOS can be due to various
      causes and a team approach, which is one of the requirements of clinical
      governance approach, is needed to manage it. The results showed that the
      multidisciplinary team could make positive changes and reduce LOS in emergency
      setting.

PMID- 24659073
TI  - Cross-shift study of acute respiratory effects in cement production workers.
AB  - Cement dust exposure is associated with increased respiratory impairment. As the
      major occupational hazard in the cement production industry is cement particles,
      our aim was to more thoroughly examine the acute effects of occupational exposure
      to cement dust on the respiratory system. A cross-shift study was conducted in a
      cement factory in Iran. 100 high exposed workers from production and packing
      sections and 100 low exposed from office workers were included. Environmental
      total dust was measured in each section. Assessment of lung function was done by
      pre and post shift spirometry. At the end of the day shift, acute respiratory
      symptoms were recorded. The means of total dust among high and low exposed
      workers were 16.55 mg/m3 and 0.9 mg/m3, respectively. The most common acute
      respiratory symptoms in high exposed workers were stuffy nose (52%) and shortness
      of breath (49%). A statistically significant post shift reduction in PEF, FEV1,
      FEF 25-75, FVC and FEV1/ FVC was demonstrated in high exposed group. Multivariate
      linear regression showed a significant relationship between the percentage of the
      cross-shift decrease in spirometric indices and exposure to cement dust. We
      detected significant relationship between exposure to cement dust and acute
      respiratory symptoms and pulmonary function indices. Effective dust-control
      measures and preparing a suitable strategy for respiratory protection are highly
      recommended.

PMID- 24659075
TI  - The trend of indexed papers in PubMed covering different aspects of self
      immolation.
AB  - Self-immolation is a fatal and devastating method of committing suicide used
      around the world. The chief aim of the present article is to look at the trend of
      indexed papers in PubMed covering different aspects of self-immolation. PubMed
      search engine (http://www.ncbi.nlm.nih.gov) was searched by using six keywords
      i.e. "self-immolation", "self-inflicted burn", "self-burning", "self
      incineration", "suicidal burns" and "suicide by burning". These keywords should
      appear either in the title or the abstract of the articles. The time frame was
      set as to retrieve papers expanding from early indexing time up to end of the
      year 2011. Based on the search strategy 132 papers were retrieved from these
      total numbers; 12 (9%) were categorized as review papers; 24 (18%) as case
      reports and the rest 96 (73%) were original studies. It seems that the number of
      papers increased during the years of investigations and the highest indexed
      papers i.e. 14 (10.6%) belonged to the year 2011. While most journals, published
      only one article the highest indexed papers i.e. 35 (26.5%) belonged to Burns.
      There was an increasing trend in the number of self-immolation articles indexed
      in PubMed since 1965. Three journals i.e. Burns, Journal of Burn Care and
      Rehabilitation and Journal of Forensic Sciences hosted for more than 37% of all
      those indexed articles. However, given the increasing trend of self-immolation
      still more studies are needed to shed light on the diverse aspects of this
      appalling human behavior. 

PMID- 24659074
TI  - Perception and use of complementary and alternative medicine among children and
      adults with epilepsy: the importance of the decision makers.
AB  - The aim of the current study was to assess the extent to which complementary and
      alternative medicine (CAM) has been used in children and adults to treat seizures
      and to compare the perceptions and usage of CAM between adult patients who
      decides for themselves and adults who decide for their sick children.In this
      cross-sectional study, patients who have been treated for epilepsy for at least
      one year at the outpatient epilepsy clinic at the Shiraz University of Medical
      Sciences were interviewed from January 2012 through March 2012. The questionnaire
      collected specific information of CAM perceptions and usage among patients.
      Pearson Chi-Square and Student's t-test were used to compare variables among
      children group with adults group. Ninety-eight children (their caregivers) and
      158 adults (themselves) participated. Adult patients (53%) more frequently
      believed that CAM might be useful in treating seizures than adults with sick kids
      (35%) (P = 0.0004). Herbal drugs, traditional medicine and exercise were more
      often considered as being helpful in treating seizures among adult patients
      compared to adults with sick children. CAM usage was not different among adult
      patients compared to adults with sick kids (P = 0.3). CAM is an option considered
      by many people with epilepsy to treat seizures. The individual who makes the
      decision as to use any of these unconventional treatment options is probably not
      different when it comes to self (the patient himself) vs. non-self (the
      parents/care-givers), despite the observed difference that adult patients more
      frequently believed that CAM might be useful in treating seizures than adults
      with sick kids.

PMID- 24659076
TI  - Familial amyloidosis cutis dyschromica: a case report.
AB  - Amyloidosis cutis dyschromica (ACD) is a rare form of macular amyloidosis
      characterized by hypo and hyperpigmented macules. Here we described a 20 year old
      girl with diffuse hypo and hyperpigmentation since she was four years old. Five
      other members of her family are also involved. Biopsy of hyperpigmented lesions
      revealed increase of melanin in the basal layer, pigment incontinence and
      amorphous eosinophilic masses stained positive with Congo red in the papillary
      dermis. The histopathologic findings were consistent with amyloidosis cutis
      dyschromica. Other investigations were normal. Dermatologists should consider
      amyloidosis cutis dyschromica when visit a patient with diffuse hypo and
      hyperpigmentation. 

PMID- 24659077
TI  - Intracortical chondrosarcoma: a case report.
AB  - Chondrosarcoma is the second most common primary mesenchymal malignant tumor of
      the bone. The most common form is central chondrosarcoma and the rarest is
      intracortical chondrosarcoma. Here, we describe the clinical, pathological, and
      imaging features of a case of intracortical chondrosarcoma as well as the outcome
      of surgical treatment. This is the third case reported in the literature. 

PMID- 24659078
TI  - Rhabdomyosarcoma with skin metastasis: report of a case.
AB  - Rhabdomyosarcomas are the most common soft tissue sarcoma in adult and children
      that accompany with skeletal muscle differentiation. Skin metastasis of
      rhabdomyosarcomas is unusual and has only been sporadically reported in
      literature. In this paper we present a case of skin metastasis of
      rhabdomyosarcoma in an 8-year-old girl that has treated with chemotherapy. 

PMID- 24659079
TI  - Complication of hemodialysis access (pseudoaneurysm): a case report.
AB  - The number of patients with end-stage renal disease has steadily increased and
      improvements in hemodialysis techniques have lead to extended life expectancy.
      Pseudoaneurysm is a relatively rare complication of autogenous vascular access.
      We have reported a case in which an anastomotic pseudoaneurysm developed in a
      patient on hemodialysis treatment. 

PMID- 24659080
TI  - Suppression of CXCL2 upregulation underlies the therapeutic effect of the
      retinoid Am80 on intracerebral hemorrhage in mice.
AB  - We previously demonstrated that a synthetic retinoic acid receptor agonist, Am80,
      attenuated intracerebral hemorrhage (ICH)-induced neuropathological changes and
      neurological dysfunction. Because inflammatory events are among the prominent
      features of ICH pathology that are affected by Am80, this study investigated the
      potential involvement of proinflammatory cytokines/chemokines in the effect of
      Am80 on ICH. ICH induced by collagenase injection into mouse striatum caused
      prominent upregulation of mRNAs for interleukin (IL)-1beta, tumor necrosis factor
      (TNF)-alpha, IL-6, CXCL1, CXCL2, and CCL3. We found that dexamethasone (DEX) and
      Am80 differently modulated the increase in expression of these
      cytokines/chemokines; TNF-alpha expression was attenuated only by DEX, whereas
      CXCL2 expression was attenuated only by Am80. Expression of IL-1beta and IL-6 was
      inhibited both by DEX and Am80. Neurological assessments revealed that Am80, but
      not DEX, significantly alleviated motor dysfunction of mice after ICH. From these
      results, we suspected that CXCL2 might be critically involved in determining the
      extent of motor dysfunction. Indeed, magnetic resonance imaging-based
      classification of ICH in individual mice revealed that invasion of hematoma into
      the internal capsule, which has been shown to cause severe neurological
      disabilities, was associated with higher levels of CXCL2 expression than ICH
      without internal capsule invasion. Moreover, a CXCR1/2 antagonist reparixin
      ameliorated neurological deficits after ICH. Overall, suppression of CXCL2
      expression may contribute to the beneficial effect of Am80 as a therapeutic agent
      for ICH, and interruption of CXCL2 signaling may provide a promising target for
      ICH therapy.

PMID- 24659081
TI  - Investigation of deletion of 22pb in KIR2DS4 gene in a population of southern
      Brazil.
AB  - BACKGROUND: The aim of this study was to investigate the distribution of full
      length and deleted variants of KIR2DS4 in a population of southern Brazil and
      compare the results with other populations, as well as comparing two techniques,
      PCR-SSP and PCR-SSO, for typing of variants. METHODS: 258 individuals from
      southern Brazil were analysed by PCR-SSO ("polymerase chain reaction-sequence
      specific oligonucleotides", One Lambda, Inc., Canoga Park, CA), of which 161 were
      also analysed by PCR-SSP. RESULTS: The study population showed similarities with
      other Caucasian populations; 46.5% of individuals had only KIR2DS4 variants,
      21.3% had the full-length form and 25.1% had both forms. CONCLUSION: The
      frequencies found in both groups (genotyped by PCR-SSP and PCR-SSO) were 100%
      concordant.

PMID- 24659082
TI  - Low dose ZD7288 attenuates the ischemia/reperfusion-induced impairment of long
      term potentiation induction at hippocampal Schaffer collateral-CA1 synapses.
AB  - Focal cerebral ischemia can impair the induction of activity-dependent long-term
      potentiation (LTP) in the hippocampus. This impairment of hippocampal synaptic
      plasticity can be caused by excitotoxicity and subsequent perturbation of
      hippocampal LTP-relevant transmitter systems, which include NR2B and PSD-95. It
      has been suggested that hyperpolarization-activated cyclic-nucleotide-gated (HCN)
      channels may play an important role in the control of membrane excitability and
      rhythmic neuronal activity. Our previous study has indicated that the selective
      HCN channel blocker ZD7288 can produce a dose-dependent inhibition of the
      induction of LTP at the Schaffer collateral-CA1 synapse of hippocampus by
      reducing the amount of glutamate released. It has also been demonstrated that
      ZD7288 can protect against neuronal injury caused by oxygen glucose deprivation.
      In the present study, we investigated the effect of ZD7288 on the induction of
      activity-dependent LTP and the expression of NR2B and PSD-95 after focal cerebral
      ischemia/reperfusion injury. The results showed that the induction of LTP was
      significantly impaired and the levels of NR2B and PSD-95 mRNA and protein were
      markedly decreased in the CA1 region of hippocampus following focal cerebral
      ischemia/reperfusion injury. Administration of low dose ZD7288 (0.25 MUg) at 30
      min and 3 h after the onset of ischemia attenuated the impairment of LTP
      induction and alleviated the NR2B and PSD-95 mRNA and protein down-regulation
      commonly induced by cerebral ischemia/reperfusion injury. These results suggest
      that low dose ZD7288 can ameliorate the ischemia/reperfusion-induced impairment
      of synaptic plasticity in the hippocampal CA1 region.

PMID- 24659083
TI  - Is postdilatation useful after implantation of the Edwards valve?
AB  - BACKGROUND: Few data are available about postdilatation (PD) for the treatment of
      significant paravalvular aortic regurgitation (AR) after transcatheter aortic
      valve implantation of the Edwards valve. METHODS AND RESULTS: A total of 470
      patients, aged 83.4 +/- 6.4 yrs, with logistic European System for Cardiac
      Operative Risk Evaluation 21.9 +/- 12.3, undergoing transcatheter aortic valve
      implantation with the Edwards valve were evaluated. PD was performed using the
      balloon delivery system when significant paravalvular AR was identified. The
      diameter of the valve was measured from cine acquisition at three different
      levels. PD was performed in 49 (10.4%) patients with grade 2, 3, or 4 AR as
      42.1%, 55.3%, and 2.6%, respectively. After PD, a reduction of at least 1 degree
      of AR was achieved in 81.5% of cases. Residual AR grades 2, 3, and 4 were
      observed in 36.8%, 10.5%, and 0%, respectively. A significant increase in the
      prosthesis diameter was observed at the three valve levels (absolute Delta 3.5%
      5.4%, P.< 0.01). For the 23 mm valve, mid level of valve increased from 23.0 +/-
      0.4 to 24.1 +/- 0.5 mm (P < 0.01) and for the 26 mm, from 25.2 +/- 0.9 to 26.6 +/
      0.9 mm (P < 0.01). Occurrence of annulus rupture (4.1% vs. 1.7%, P = 0.24),
      cerebrovascular accidents (2.0% vs. 2.1%, P = 0.72), need for new pacemaker (8.2%
      vs. 5.5%, P = 0.31), and 30-day composite endpoint (24.5% vs. 20.2%, P = 0.48)
      were not significantly different between PD and non-PD groups. CONCLUSIONS: PD
      for the treatment of significant paravalvular leak proved to be a feasible
      treatment allowing a significant increase in valve size and decrease in PVL
      without increase in stroke rates. This promising approach needs further
      confirmation.

PMID- 24659084
TI  - The role of rivaroxaban in atrial fibrillation and acute coronary syndromes.
AB  - Rivaroxaban, a direct factor Xa inhibitor, is a novel oral anticoagulant approved
      for stroke prevention in patients with nonvalvular atrial fibrillation and also
      approved in Europe (but not in the United States) to prevent recurrent ischemic
      events in patients with recent acute coronary syndromes. Advantages of
      rivaroxaban over oral anticoagulants such as warfarin are the lack of need for
      ongoing monitoring, a fixed-dose regimen, and fewer drug and food interactions.
      Drawbacks include a lack of an antidote and the absence of a widely available
      method to reliably monitor the anticoagulant effect. In patients at risk of
      stroke due to atrial fibrillation, rivaroxaban was noninferior compared to
      warfarin in preventing stroke/systemic embolism in the Rivaroxaban Once Daily
      Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for
      Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial
      and was associated with a similar risk of major bleeding; the incidence of
      intracranial hemorrhage was 33% lower with rivaroxaban. Concerns raised about the
      trial were the adequacy of warfarin management and the increase in event rate at
      the end of the trial. The drug acquisition cost of rivaroxaban is higher than
      that of warfarin although decision-analytic models suggest that it is cost
      effective in atrial fibrillation. In patients with recent acute coronary
      syndrome, low-dose rivaroxaban reduced mortality and the composite end point of
      death from cardiovascular causes, myocardial infarction and stroke, but this was
      accompanied by an increased risk of intracranial hemorrhage and major bleeding in
      the Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a
      Thienopyridine in Patients With Acute Coronary Syndromes-Thrombolysis in
      Myocardial Infarction (ATLAS ACS 2-TIMI) 51 trial. Thus, rivaroxaban appears to
      be a valuable addition to the therapeutic armamentarium in atrial fibrillation
      although caution should be exercised, given the limited experience in combination
      with novel oral antiplatelet agents. The role of rivaroxaban as part of a modern
      regimen in acute coronary syndrome continues to be evaluated. 

PMID- 24659085
TI  - Response to "The neglected cranial nerve: nervus terminalis (cranial nerve N)".

PMID- 24659087
TI  - Periodontitis in older Swedish individuals fails  to predict mortality.
AB  - OBJECTIVES: This study aims to assess mortality risk and its association to
      health aspects in dentate individuals 60 years of age and older. MATERIALS AND
      METHODS: Medical and periodontal data from 870 dentate individuals (age range 60
      96) participating in the Swedish National Study on Aging and Care in Blekinge
      (SNACBlekinge)with survival statistics over 6 years were studied. RESULTS: During
      6 years of follow-up, 42/474 of the individuals(8.9 %), who at baseline were
      between age 60 and 75, and 134/396 individuals of the individuals (33.9 %), who
      at baseline were >=75 years, died. Surviving dentate individuals had more teeth
      (mean 19.3, S.D.+/-7.9) than those who died (mean 15.9,S.D.+/-7.3; mean diff 3,3;
      S.E. mean diff 0.7; 95 % CI 2.0, 4.6;p=0.001). A self-reported history of high
      blood pressure (F=15.0, p<0.001), heart failure (F=24.5, p<0.001, observed
      power=0.99), older age (F=34.7, p<0.001), male gender(F=6.3, p<0.01), serum HbA1c
      with 6.5 % as cutoff level(F=9.3, p=0.002) were factors associated with
      mortality. A medical diagnosis of heart disease, diabetes, any form of cancer,or
      periodontitis failed to predict mortality. CONCLUSIONS: A self-reported history
      of angina pectoris, chronic heart failure, elevated serum HbA1c, and few
      remaining teeth were associated with mortality risk. A professional diagnosis of
      cardiovascular disease, diabetes, cancer, or periodontitis was not predictive of
      mortality. CLINICAL RELEVANCE: Self-health reports are important to observe in
      the assessment of disease and survival in older individual.

PMID- 24659086
TI  - Photosynthetic biomanufacturing in green algae; production of recombinant
      proteins for industrial, nutritional, and medical uses.
AB  - Recombinant proteins are widely used for industrial, nutritional, and medical
      applications. Green microalgae have attracted considerable attention recently as
      a biomanufacturing platform for the production of recombinant proteins for a
      number of reasons. These photosynthetic eukaryotic microorganisms are safe,
      scalable, easy to genetically modify through transformation, mutagenesis, or
      breeding, and inexpensive to grow. Many microalgae species are genetically
      transformable, but the green alga Chlamydomonas reinhardtii is the most widely
      used host for recombinant protein expression. An extensive suite of molecular
      genetic tools has been developed for C. reinhardtii over the last 25 years,
      including a fully sequenced genome, well-established methods for transformation,
      mutagenesis and breeding, and transformation vectors for high levels of
      recombinant protein accumulation and secretion. Here, we review recent successes
      in the development of C. reinhardtii as a biomanufacturing host for recombinant
      proteins, including antibodies and immunotoxins, hormones, industrial enzymes, an
      orally-active colostral protein for gastrointestinal health, and subunit
      vaccines. In addition, we review the biomanufacturing potential of other green
      algae from the genera Dunaliella and Chlorella.

PMID- 24659088
TI  - Advances in induced pluripotent stem cells, genomics, biomarkers, and
      antiplatelet therapy highlights of the year in JCTR 2013.
AB  - The Journal provides the clinician and scientist with the latest advances in
      discovery research, emerging technologies, preclinical research design and
      testing, and clinical trials. We highlight advances in areas of induced
      pluripotent stem cells, genomics, biomarkers, multimodality imaging, and
      antiplatelet biology and therapy. The top publications are critically discussed
      and presented along with anatomical reviews and FDA insight to provide context.

PMID- 24659089
TI  - Intimate partner violence and women's economic and non-economic activities in
      Minya, Egypt.
AB  - Intimate partner violence (IPV) against women is widespread, but its implications
      for their economic and non-economic activities are understudied. Leveraging new
      data from 564 ever-married women aged 22-65 in rural Minya, Egypt, we estimated
      logistic regressions and zero-inflated negative binomial regressions to test
      spillover, compensation, and patriarchal bargaining theories about the influences
      of women's exposure to IPV on their engagement in and time spent on market,
      subsistence, domestic, and care work. Supporting compensation theory, exposures
      to lifetime, recent, and chronic physical or sexual IPV were associated with
      higher adjusted odds of performing market work in the prior month, and exposures
      to recent and chronic IPV were associated with higher adjusted odds of performing
      subsistence work in this period. Supporting compensation and patriarchal
      bargaining theories, exposures to recent and chronic IPV were associated with
      more time spent on domestic work in the prior day. Supporting spillover and
      patriarchal bargaining theories, exposures to lifetime IPV of all forms were
      associated with lower adjusted odds of performing mostly nonspousal care work in
      the prior day, and this association was partially mediated by women's generalized
      anxiety. Women in rural Minya who are exposed to IPV may escalate their housework
      to fulfill local norms of feminine domesticity while substituting economic
      activities for nonspousal care work to enhance their economic independence from
      violent partners.

PMID- 24659090
TI  - Does contraceptive use always reduce breast-feeding?
AB  - Previous studies suggest that access to modern contraceptives can reduce breast
      feeding rates because women who had been using breast-feeding to avoid pregnancy
      substitute away from it. This article shows that contraceptive use can also have
      a positive effect on breast-feeding. A mother often weans a child if she becomes
      pregnant again, which can occur sooner than desired if she lacks access to
      contraceptives. Thus, by enabling longer birth spacing and preventing unwanted
      pregnancies, contraceptive use allows for a longer duration of breast-feeding.
      This positive effect should primarily affect infants who are past the first few
      months of life because their mothers are more fecund then, and the negative
      effect should affect infants who are very young because the contraceptive
      property of breast-feeding is strongest then. I test for these dual effects using
      Demographic and Health Survey data for Indonesia. I find evidence of the positive
      birth-spacing effect: contraceptive use increases the likelihood that children
      continue to be breast-fed past age 1. There is also suggestive evidence of a
      negative substitution effect among infants age 3 months and younger.

PMID- 24659091
TI  - Short-term effect of unilateral pedicle screw fixed intervertebral fusion in
      treatment of degenerative disc disease via MAST QUADRANT minimally invasive
      system.
AB  - To assess the short-term outcome of unilateral pedicle screw fixed intervertebral
      fusion surgery for degenerative disc disease via MAST QUADRANT minimally invasive
      system. Thirty patients with degenerative lumbar disease from September 2009 to
      September 2011 were enrolled and divided into two groups: (1) unilateral pedicle
      screw fixed intervertebral fusion via MAST QUADRANT system; and (2) conventional
      bilateral pedicle fixed intervertebral fusion via open surgery. The perioperative
      parameters (operation time, intraoperative blood loss, and length of stay) and
      the follow-up clinical curative effect parameters (VAS and ODI) were compared
      between two groups. All patients successfully completed surgery and were followed
      up for more than 1 year. The perioperative parameters of MAST QUADRANT system
      group were significantly better than the control group (P < 0.05). And the
      clinical curative effects were similar to conventional surgery (P > 0.05).
      Unilateral pedicle screw fixed intervertebral fusion via MAST QUADRANT system is
      a less invasive and safer surgical techniques. It offers a quick recovery and
      effective surgical option in the treatment of lumbar degenerative diseases.

PMID- 24659092
TI  - Analysis of the relationship between ultrasound of breast cancer DOT-SDI and the
      expression of MVD, VEGF and HIF-1alpha.
AB  - Ultrasonic light scattering tomography system is a new imaging technique for
      breast function, which associates with diffused optical tomography (DOT) with
      ultrasonic examination. It locates breast neoplasm with ultrasonic examination
      and measures the total hemoglobin concentration inside the tumor with DOT photon
      emission to reflect the metabolic state of tumors and then comes to synthesis
      diagnostic index to judge benign and malignant tumors. This diagnosis method has
      significant affection on diagnosis of benign and malignant tumors at home and
      abroad. In the development of breast cancer, local tissue hypoxia leads to a
      large number of new blood vessels when the tumor grows faster than the rate of
      angiogenesis. A recent study found microvessel density (MVD), vascular
      endothelial growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF
      1alpha) play a major role in angiogenesis of breast cancer. This study analyses
      the relationship between breast cancer ultrasound synthesis diagnostic index
      (SDI) and the expression of MVD, VEGF and HIF-1alpha by testing the expression
      level of the breast cancer gene MVD, VEGF and HIF-1alpha.

PMID- 24659093
TI  - Expression and mechanism of BRP-39 in bleomycin-induced pulmonary fibrosis in
      rat.
AB  - The purpose of the study was to explore the effects of breast regression protein
      39 (BRP-39) in bleomycin-induced pulmonary fibrosis and its mechanism in
      pulmonary fibrosis by studying change in BRP-39 to provide a novel direction for
      the treatment of idiopathic pulmonary fibrosis. SPF grade male C57BL/6 rats were
      randomly divided into three groups, including bleomycin group, bleomycin+ BRP-39
      recombinant protein group and control group. HE and Masson staining were applied
      to test the change in lung tissue after being treated by BRP-39, ELISA was
      applied to test the expression of TGF-beta1 in different groups, and Western blot
      was used to test the expression of BRP-39 in rat lung tissue. Expression of BRP
      39 increased, the fibrosis was obvious, and lung tissue collagen increased in
      bleomycin-induced pulmonary fibrosis in rat lung tissue. Increasing BRP-39
      protein level and intratracheal bleomycin medication to establish pulmonary
      fibrosis model can aggravate pulmonary fibrosis. Along with the increase in BRP
      39 protein level, TGF-beta1 expression level also increased in lung tissue.
      Western blot results showed the expression of BRP-39, and TGF-beta1 had the same
      trend in different groups. BRP-39 has effects in bleomycin-induced rat pulmonary
      fibrosis. Change in BRP-39 can affect the process of bleomycin-induced pulmonary
      fibrosis. The mechanism of BRP-3 in pulmonary fibrosis may work by regulating TGF
      beta1.

PMID- 24659094
TI  - A new flow cytometric method for differential cell counting in ascitic fluid.
AB  - BACKGROUND: Cell counts in bodyfluids such as ascitic fluid can be difficult to
      perform and report rapidly. The current gold standard for cell counting in body
      fluids is a suitable automated cell counter or a manual counting chamber,
      combined with differential counting on a cytospin. This technique has several
      disadvantages, so we designed a new flow cytometric test for cell counting in
      ascites. We compared this with an automatic cell counter (LH750, Beckman Coulter)
      and manual counting of cytospins. METHODS: Ascitic samples (n = 53) from 38
      patients were studied. Polymorphonuclear neutrophils (PMN), lymphocytes,
      eosinophils, and macrophages were defined by flow cytometry. We compared this
      with our reference method: the absolute cell concentration calculated from the
      leukocyte concentration of the LH750 combined with a differential cell count
      performed manually on a cytospin. RESULTS: The outcomes of validation experiments
      (linearity, reproducibility, and detection limit) of the flow cytometric assay
      prove it is well suited for cell counting in ascitic fluid. CONCLUSIONS: Based on
      analytical performance, flow cytometry is suited for cell counting in ascitic
      fluid. An ascitic fluid cell count is frequently ordered to detect spontaneous
      bacterial peritonitis (SBP). If the PMN count is >=250 cells/mm3 , SBP is highly
      suspected. Using our reference method, we calculated the sensitivities and
      specificities to detect >=250 PMN cells/mm3 for the LH750 (100% and 65%,
      respectively) and flow cytometric assay (100%, 100%). As flow cytometry is easier
      and faster we recommend this method for rapid cell counting in ascitic fluid. (c)
      2014 International Clinical Cytometry Society.

PMID- 24659095
TI  - [Rituximab for treatment of Felty's syndrome].
AB  - Felty's syndrome is a rare variant of severe seropositive rheumatoid arthritis
      with neutropenia and splenomegaly. It is difficult to treat and associated with a
      poor prognosis due to the substantial risk of infections. This article presents
      the case of a patient with refractory disease who responded to rituximab with
      permanent normalization of neutrophil counts. Repeated infusions were necessary
      to induce and maintain remission.

PMID- 24659096
TI  - Neural organization of the second optic neuropil, the medulla, in the highly
      visual semiterrestrial crab Neohelice granulata.
AB  - Crustaceans are widely distributed and inhabit very different niches. Many of
      them are highly visual animals. Nevertheless, the neural composition of
      crustacean optic neuropils deeper than the lamina is mostly unknown. In
      particular, semiterrestrial crabs possess a highly developed visual system and
      display conspicuous visually guided behaviors. A previous study shows that the
      first optic neuropil, the lamina of the crab Neohelice granulata, possesses a
      surprisingly high number of elements in each cartridge. Here, we present a
      comprehensive description of individual elements composing the medulla of that
      same species. Using Golgi impregnation, we characterized a wide variety of cells.
      Only considering the class of transmedullary neurons, we describe over 50
      different morphologies including small- and large-field units. Among others, we
      describe a type of centrifugal neuron hitherto not identified in other
      crustaceans or insects that probably feeds back information to every cartridge in
      the medulla. The possible functional role of such centrifugal elements is
      discussed in connection with the physiological and behavioral information on
      visual processing available for this crab. Taken together, the results reveal a
      very dense and complex neuropil in which several channels of information
      processing would be acting in parallel. We further examine our results
      considering the similarities and differences found between the layered
      organization and components of this crustacean medulla and the medullae of
      insects.

PMID- 24659097
TI  - The fluxes of H2O2 and O2 can be used to evaluate seed germination and vigor of
      Caragana korshinskii.
AB  - Seed deterioration is detrimental to plant germplasm conservation, and predicting
      seed germination and vigor with reliability and sensitivity means is urgently
      needed for practical problems. We investigated the link between hydrogen peroxide
      (H2O2) flux, oxygen influx and seed vigor of Caragana korshinskii by the non
      invasive micro-test technique (NMT). Some related physiological and biochemical
      changes in seeds were also determined to further explain the changes in the
      molecular fluxes. The results showed that there was a good linear relationship
      between germination and H2O2 flux, and that O2 influx was more suitable for
      assessing seed vigor. H2O2 flux changed relatively little initially, mainly
      affected by antioxidants (APX, CAT and GSH) and H2O2 content; afterward, the
      efflux increased more and more rapidly due to high membrane permeability. With
      the damage of mitochondrial respiration and membrane integrity, O2 influx was
      gradually reduced. We propose that monitoring H2O2 and O2 fluxes by NMT may be a
      reliable and sensitive method to evaluate seed germination and vigor.

PMID- 24659099
TI  - Anomalous electrophoretic migration of short oligodeoxynucleotides labelled with
      5'-terminal Cy5 dyes.
AB  - By using a fluorescent exonuclease assay, we reported unusual electrophoretic
      mobility of 5'-indocarbo-cyanine 5 (5'-Cy5) labelled DNA fragments in denaturing
      polyacrylamide gels. Incubation time and enzyme concentration were two parameters
      involved in the formation of 5'-Cy5-labelled degradation products, while the
      structure of the substrate was slightly interfering. Replacement of positively
      charged 5'-Cy5-labelled DNA oligonucleotides (DNA oligos) by electrically neutral
      5'-carboxyfluorescein (5'-FAM) labelled DNA oligos abolished the anomalous
      migration pattern of degradation products. MS analysis demonstrated that
      anomalously migrating products were in fact 5'-labelled DNA fragments ranging
      from 1 to 8 nucleotides. Longer 5'-Cy5-labelled DNA fragments migrated at the
      expected position. Altogether, these data highlighted, for the first time, the
      influence of the mass/charge ratio of 5'-Cy5-labelled DNA oligos on their
      electrophoretic mobility. Although obtained by performing 3' to 5' exonuclease
      assays with the family B DNA polymerase from Pyrococcus abyssi, these
      observations represent a major concern in DNA technology involving most DNA
      degrading enzymes.

PMID- 24659100
TI  - Bioactivity of porous biphasic calcium phosphate enhanced by recombinant human
      bone morphogenetic protein 2/silk fibroin microsphere.
AB  - To prepare a bioactive bone substitute, which integrates biphasic calcium
      phosphate (BCP) and rhBMP-2/silk fibroin (SF) microsphere, and to evaluate its
      characteristics. Hydroxyapatite and beta-tricalcium phosphate were integrated
      with a ratio of 60-40%. RhBMP-2/SF (0.5 MUg/1 mg) microsphere was prepared, and
      its rhBMP-2-release kinetics was assed. After joining pore-forming agent (Sodium
      chloride, NaCl), porous BCP/rhBMP-2/SF were manufactured, and its characteristics
      and bioactivity in vitro were evaluated. Mean diameter of rhBMP-2/SF microsphere
      was 398.7 +/- 99.86 nm, with a loading rate of 4.53 +/- 0.08%. RhBMP-2 was
      released in a dual-phase pattern, of which fast-release (nearly half of protein
      released) focused on the initial 3 days, and slow-release sustained more than 28
      days. With the increase in concentration of NaCl, greater was porosity and pore
      size, but smaller mechanical strength of BCP/rhBMP-2/SF. Material with 150% (w/v)
      NaCl had an optimal performance, with a porosity of 78.83%, pore size of 293.25
      +/- 42.77MUm and mechanical strength of 31.03 MPa. Proliferation of human
      placenta-derived mesenchymal stem cells (hPMSCs) on leaching extract medium was
      similar to the normal medium (P = 0.89), which was better than that on control
      group (P = 0.03). Activity of alkaline phosphatase on BCP/rhBMP-2/SF surface was
      higher than on pure BCP at each time point except at 1 day (P < 0.05). RhBMP-2
      has a burst release on early times and a sustaining release on later times.
      BCP/rhBMP-2/SF with 150% (w/v) pore-forming agent has excellent porosity, pore
      size and mechanical strength. The biomaterial induces proliferation and
      differentiation hPMSCs effectively.

PMID- 24659101
TI  - Breast cancer-associated protein--a novel binding partner of Mason-Pfizer monkey
      virus protease.
AB  - We identified breast cancer-associated protein (BCA3) as a novel binding partner
      of Mason-Pfizer monkey virus (MPMV) protease (PR). The interaction was confirmed
      by co-immunoprecipitation and immunocolocalization of MPMV PR and BCA3. Full
      length but not C-terminally truncated BCA3 was incorporated into MPMV virions. We
      ruled out the potential role of the G-patch domain, a glycine-rich domain located
      at the C terminus of MPMV PR, in BCA3 interaction and virion incorporation.
      Expression of BCA3 did not affect MPMV particle release and proteolytic
      processing; however, it slightly increased MPMV infectivity.

PMID- 24659102
TI  - Genetic characterization of a novel duck-origin picornavirus with six 2A
      proteins.
AB  - A novel virus was detected from diseased ducks and completely determined. The
      virus was shown to have a picornavirus-like genome layout. Interestingly, the
      genome contained a total of up to six 2As, including four 2As (2A1-2A4) each
      having an NPGP motif, an AIG1-like 2A5, and a parechovirus-like 2A6. The 5'UTR
      was predicted to possess a hepacivirus/pestivirus-like internal ribosome entry
      site (IRES). However, the subdomain IIIe consisted of a 3 nt stem and five
      unpaired bases, distinct from those found in all other HP-like IRESs. The virus
      was most closely related to duck hepatitis A virus, with amino acid identities of
      37.7 %, 39 % and 43.7 % in the P1, P2 and P3 regions, respectively. Based on
      these investigations, together with phylogenetic analyses, the virus could be
      considered as the founding member of a novel picornavirus genus that we
      tentatively named 'Aalivirus', with 'Aalivirus A' as the type species.

PMID- 24659098
TI  - The roles of polyamines during the lifespan of plants:  from development to
      stress.
AB  - Compelling evidence indicates that free polyamines (PAs) (mainly putrescine,
      spermidine, spermine, and its isomer thermospermine), some PA conjugates to
      hydroxycinnamic acids, and the products of PA oxidation (hydrogen peroxide and
      gamma-aminobutyric acid) are required for different processes in plant
      development and participate in abiotic and biotic stress responses. A tight
      regulation of PA homeostasis is required, since depletion or overaccumulation of
      PAs can be detrimental for cell viability in many organisms. In plants,
      homeostasis is achieved by modulation of PA biosynthesis, conjugation,
      catabolism, and transport. However, recent data indicate that such mechanisms are
      not mere modulators of PA pools but actively participate in PA functions.
      Examples are found in the spermidine-dependent eiF5A hypusination required for
      cell division, PA hydroxycinnamic acid conjugates required for pollen
      development, and the involvement of thermospermine in cell specification. Recent
      advances also point to implications of PA transport in stress tolerance, PA
      dependent transcriptional and translational modulation of genes and transcripts,
      and posttranslational modifications of proteins. Overall, the molecular
      mechanisms identified suggest that PAs are intricately coordinated and/or mediate
      different stress and developmental pathways during the lifespan of plants.

PMID- 24659103
TI  - Guinea pig cytomegalovirus GP129/131/133, homologues of human cytomegalovirus
      UL128/130/131A, are necessary for infection of monocytes and macrophages.
AB  - The GP129, GP131 and GP133 genes of guinea pig cytomegalovirus (GPCMV) are
      homologues of human cytomegalovirus UL128, UL130 and UL131A, respectively, which
      are essential for infection of endothelial and epithelial cells, and for viral
      transmission to leukocytes. Our previous study demonstrated that a GPCMV strain
      lacking the 1.6 kb locus that contains the GP129, GP131 and GP133 genes had a
      growth defect in animals. Here, we demonstrated that the WT strain, but not the
      1.6 kb-deleted strain, formed capsids in macrophages prepared from the peritoneal
      fluid. To understand the mechanism, we prepared GPCMV strains defective in each
      of GP129, GP131 and GP133, and found that they were all essential for the
      infection of peritoneal, splenic and PBMC-derived macrophages/monocytes, and for
      expression of immediate-early antigens in the macrophages/monocytes, although
      they were dispensable for infection of fibroblasts. Monocyte/macrophage tropism
      could be one of the important determinants for viral dissemination in vivo.

PMID- 24659104
TI  - GOssTo: a stand-alone application and a web tool for calculating semantic
      similarities on the Gene Ontology.
AB  - SUMMARY: We present GOssTo, the Gene Ontology semantic similarity Tool, a user
      friendly software system for calculating semantic similarities between gene
      products according to the Gene Ontology. GOssTo is bundled with six semantic
      similarity measures, including both term- and graph-based measures, and has
      extension capabilities to allow the user to add new similarities. Importantly,
      for any measure, GOssTo can also calculate the Random Walk Contribution that has
      been shown to greatly improve the accuracy of similarity measures. GOssTo is very
      fast, easy to use, and it allows the calculation of similarities on a genomic
      scale in a few minutes on a regular desktop machine. CONTACT:
      alberto@cs.rhul.ac.uk AVAILABILITY: GOssTo is available both as a stand-alone
      application running on GNU/Linux, Windows and MacOS from
      www.paccanarolab.org/gossto and as a web application from
      www.paccanarolab.org/gosstoweb. The stand-alone application features a simple and
      concise command line interface for easy integration into high-throughput data
      processing pipelines.

PMID- 24659105
TI  - massiR: a method for predicting the sex of samples in gene expression microarray
      datasets.
AB  - High-throughput gene expression microarrays are currently the most efficient
      method for transcriptome-wide expression analyses. Consequently, gene expression
      data available through public repositories have largely been obtained from
      microarray experiments. However, the metadata associated with many publicly
      available expression microarray datasets often lacks sample sex information,
      therefore limiting the reuse of these data in new analyses or larger meta
      analyses where the effect of sex is to be considered. Here, we present the massiR
      package, which provides a method for researchers to predict the sex of samples in
      microarray datasets. Using information from microarray probes representing Y
      chromosome genes, this package implements unsupervised clustering methods to
      classify samples into male and female groups, providing an efficient way to
      identify or confirm the sex of samples in mammalian microarray datasets.
      AVAILABILITY AND IMPLEMENTATION: massiR is implemented as a Bioconductor package
      in R. The package and the vignette can be downloaded at bioconductor.org and are
      provided under a GPL-2 license.

PMID- 24659106
TI  - Improved transcript isoform discovery using ORF graphs.
AB  - MOTIVATION: High-throughput sequencing of RNA in vivo facilitates many
      applications, not the least of which is the cataloging of variant splice isoforms
      of protein-coding messenger RNAs. Although many solutions have been proposed for
      reconstructing putative isoforms from deep sequencing data, these generally take
      as their substrate the collective alignment structure of RNA-seq reads and ignore
      the biological signals present in the actual nucleotide sequence. The majority of
      these solutions are graph-theoretic, relying on a splice graph representing the
      splicing patterns and exon expression levels indicated by the spliced-alignment
      process. RESULTS: We show how to augment splice graphs with additional
      information reflecting the biology of transcription, splicing and translation, to
      produce what we call an ORF (open reading frame) graph. We then show how ORF
      graphs can be used to produce isoform predictions with higher accuracy than
      current state-of-the-art approaches. AVAILABILITY AND IMPLEMENTATION: RSVP is
      available as C++ source code under an open-source licence: http://ohlerlab.mdc
      berlin.de/software/RSVP/.

PMID- 24659107
TI  - The HSE Management Standards Indicator Tool: concurrent and construct validity.
AB  - BACKGROUND: The Health & Safety Executive Management Standards Indicator Tool
      (HSE-MS IT) is a questionnaire commonly used to assess work-related stress risks
      at an organizational level. A critical factor in determining whether this
      instrument is actually useful is that higher levels of stress risk in the work
      design domains should predict higher levels of stress and stress-related outcomes
      in workers. Only a few studies, however, have addressed this issue. AIMS: To test
      both the concurrent and construct validity of the HSE-MS IT, by relating it with
      another widely used instrument, the Job Content Questionnaire (JCQ), and by
      examining its relationships with a set of work-related stress outcomes. METHODS:
      An anonymous cross-sectional questionnaire was administered to a sample of
      employees in an Italian municipality. The questionnaire included the HSE-MS IT,
      self-reported measures of job satisfaction, job motivation and stress at work,
      the Satisfaction with Life Scale and the reduced form of the JCQ. RESULTS: A
      total of 760 out of 779 employees completed the questionnaire. Results showed
      moderate to strong correlation among the corresponding HSE-MS IT and JCQ scales.
      Hierarchical regression highlighted the specific contribution of each of the HSE
      MS IT scales in predicting three relevant work-related stress outcomes (self
      reported stress, job satisfaction and job motivation), after controlling for
      gender, age and life satisfaction. CONCLUSIONS: Our findings consolidated the HSE
      MS IT validity and showed the specific sensitivity of its scales to assess
      different aspects of work-related distress, including self-perception of stress
      at work. These results can have practical implications for the occupational well
      being of employees.

PMID- 24659108
TI  - On-call work and physicians' well-being: testing the potential mediators.
AB  - BACKGROUND: On-call duties have been rated to be among the most stressful aspects
      of physicians' work. On-call work has been associated, for example, with medical
      errors, injuries and lower well-being. Thus, because it is not possible to remove
      on-call duties, measures to decrease the negative ramifications of on-call work
      are needed. AIMS: To examine whether working on-call would predict psychological
      distress, job satisfaction and work ability in a 4-year follow-up and whether
      sleeping problems or work interference with family (WIF) would act as mechanisms
      in these associations. METHODS: Questionnaires in 2006 and 2010 among physicians
      in Finland. The mediation analyses were conducted using methods suggested by
      Preacher and Hayes to examine direct and indirect effects with multiple
      mediators. RESULTS: There were 1541 respondents (60% women) of whom 52% had on
      call duties. Sleeping problems and WIF acted as mechanisms in the association of
      existence of on-call duties with high distress, low job satisfaction and low work
      ability. On-call work was associated with higher levels of sleeping problems and
      WIF, and the number of active on-call hours was associated with higher levels of
      WIF, but not with sleeping problems. CONCLUSIONS: According to our results, one
      way to attenuate on-call work's negative ramifications is to make it easier for
      on-call physicians to connect work and family lives and develop work arrangements
      to promote better sleep and protected sleep time.

PMID- 24659109
TI  - The burden of influenza-like illness in the US workforce.
AB  - BACKGROUND: The disease burden of influenza-like illnesses (ILIs) on the working
      population has been documented in the literature, but statistical evidence of ILI
      related work absenteeism in the USA is limited due to data availability. AIMS: To
      assess work absenteeism due to ILIs among privately insured employees in the USA
      in 2007-8 and 2008-9. METHODS: We used the 2007-9 MarketScan(r) research
      databases. Full-time employees aged 18-64 years, with the ability to incur work
      absence and continuously enrolled in the same insurance plan during each season
      were included. We identified ILI episodes using ICD-9 codes for influenza and
      pneumonia (480-487). For each season, we calculated the mean work-loss hours per
      ILI episode and the proportion of employees who had at least one ILI episode.
      Work-loss hours and ILI rates were examined by subgroups. RESULTS: The mean
      number of work hours lost per ILI episode was 23.6 in 2007-8 and 23.9 in 2008-9.
      The proportion of employees with at least one ILI was 1.7% in 2007-8 and 1.2% in
      2008-9. In both seasons, the proportion with ILI was higher among older (2.1 and
      1.5%) and hourly workers (2.0 and 1.3%), workers in the southern region (1.9 and
      1.3%) and those in oil, gas or mining industries (1.9 and 1.4%). CONCLUSIONS: Our
      results indicate that the disease burden associated with ILIs in the working
      population is not trivial and deserves attention from policymakers and health
      care professionals to design effective strategies to reduce this burden.

PMID- 24659110
TI  - Cross-sectional associations of food consumption with plasma fatty acid
      composition and estimated desaturase activities in Finnish children.
AB  - Plasma fatty acid (FA) composition is known to be an indicator of dietary fat
      quality, but the associations of other dietary factors with plasma FA composition
      remain unknown in children. We investigated the cross-sectional associations of
      food consumption with the proportions of FA and estimated desaturase activities
      in plasma cholesteryl esters (CE) and phospholipids (PL) among children. The
      subjects were a population sample of 423 children aged 6-8 years examined at
      baseline of The Physical Activity and Nutrition in Children (PANIC) Study. We
      assessed food consumption by food records and plasma FA composition by gas
      chromatography. We used linear regression models adjusted for age, sex, physical
      activity and total energy intake to analyze the associations. A higher
      consumption of vegetable oil-based margarine (fat 60-80 %) was associated with a
      higher proportion of linoleic and alpha-linolenic acids in plasma CE and PL. A
      higher consumption of high-fiber grain products was related to a lower proportion
      of oleic acid in CE and PL. The consumption of candy was directly associated with
      the proportion of palmitoleic and oleic acid in plasma CE. The consumption of
      vegetable oil-based margarine was inversely associated with estimated stearoyl
      CoA-desaturase activity in plasma CE and PL and the consumption of candy was
      directly related to it in plasma CE. The results of our study suggest that plasma
      FA composition is not only a biomarker for dietary fat quality but also reflects
      the consumption of high-fiber grain products and foods high in sugar among
      children.

PMID- 24659111
TI  - PCSK9 is present in human cerebrospinal fluid and is maintained at remarkably
      constant concentrations throughout the course of the day.
AB  - Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of serum
      low density lipoprotein cholesterol levels. PCSK9 is secreted by the liver and
      binds the hepatic low density lipoprotein receptor, causing its subsequent
      degradation. PCSK9 has also been shown to regulate the levels of additional
      membrane-bound proteins in vitro, including very low-density lipoprotein
      receptor, apolipoprotein E receptor 2, and beta-site amyloid precursor protein
      cleaving enzyme 1, which are highly expressed in central nervous system (CNS) and
      have been implicated in Alzheimer's disease. Previous studies have demonstrated
      that human circulating PCSK9 displays a diurnal rhythm. Currently, little is
      known about PCSK9 levels in human cerebrospinal fluid (CSF). In the present
      study, we measured PCSK9 concentrations in both serum and CSF collected from
      healthy human subjects at multiple time points throughout the day. While PCSK9 in
      serum manifested a distinct diurnal pattern, CSF PCSK9 levels were remarkably
      constant throughout the course of the day and were also consistently lower than
      corresponding serum PCSK9 concentrations. Our results indicate that regulation of
      PCSK9 in human CSF may be different than for plasma PCSK9, suggesting that
      further study of the role of PCSK9 in the CNS is warranted.

PMID- 24659112
TI  - Metabolic conversion of C20 polymethylene-interrupted polyunsaturated fatty acids
      to essential fatty acids.
AB  - Polymethylene-interrupted (PMI)-polyunsaturated fatty acids (PUFA) are fatty
      acids present largely in gymnosperm. Sciadonic acid (SciA, 20:3 Delta-5,11,14)
      and juniperonic acid (JA, 20:4 Delta-5,11,14,17) are typical C20 PMI-PUFA with an
      isolated double bond at Delta5. Previously, we found that SciA and JA are
      converted to linoleic acid (LNA) and alpha-linolenic acid (AlphaLA),
      respectively. The conversion process includes chain-shortening step by
      peroxisomal beta-oxidation for elimination a double bond at Delta5, and
      subsequent chain-elongation step in microsomes. In this study, we examined the
      substrate specificity of this metabolism in rodent and human cells.
      Supplementation of SciA, eicosadienoic acid (EDA, 20:2 Delta-11,14) or JA to CHO
      K1 cells (wild type) induced an accumulation of LNA, LNA or ALA, respectively, in
      cellular lipids. These changes were not observed in the peroxisomes-deficient CHO
      cells, indicating involvement of peroxisomes in the metabolism. Two types of
      human cells (MKN74 and HepG2) also converted the C20 PMI-PUFA and EDA to the
      respective essential fatty acids. In contrast, no chain-shortened metabolite of
      pinolenic acid (18:3 Delta-5,9,12) was detected in any cell lines tested. From
      these results, C20 PMI-PUFA and EDA, but not C18 PMI-PUFA, are suggested as being
      effectively converted to essential fatty acids by the fatty acid remodeling
      system in rodent and human cells.

PMID- 24659114
TI  - Different growth sensitivity to climate of the conifer Juniperus thurifera on
      both sides of the Mediterranean Sea.
AB  - Mediterranean plants cope with cold wet winters and dry hot summers, with a
      drought gradient from northwest to southeast. Limiting climatic conditions have
      become more pronounced in the last decades due to the warming trend and rainfall
      decrease. Juniperus thurifera L., a long-lived conifer tree endemic to the
      western Mediterranean region, has a disjunct distribution in Europe and Africa,
      making it a suitable species to study sensitivity to climate in both sides of the
      Mediterranean Basin. Tree-ring width chronologies were built for three J.
      thurifera stands at Spain (Europe) and three in Morocco (Africa) and correlated
      with monthly temperature and precipitation. The temporal stability of climate
      growth relationships was assessed using moving correlations; the drought effect
      on growth was calculated using the monthly standardized precipitation
      evapotranspiration index (SPEI) at different temporal scales. In the wettest
      stands, increasing spring temperature and summer precipitation enhanced growth,
      while in the driest stands, growth was enhanced by higher spring precipitation
      and lower summer temperature. The climate-growth correlations shifted during the
      twentieth century, especially since the 1970s. Particularly noticeable is the
      recent negative correlation with previous autumn and winter precipitation in the
      wettest stands of J. thurifera, probably related with an effect of cloud cover or
      flooding on carbon storage depletion for next year growth. The driest stands were
      affected by drought at long time scales, while the wettest stands respond to
      drought at short time scales. This reveals a different strategy to cope with
      drought conditions, with populations from drier sites able to cope with short
      periods of water deficit.

PMID- 24659115
TI  - Climatic spatial variability in Extremadura (Spain) based on viticultural
      bioclimatic indices.
AB  - The evaluation of general suitability for viticulture in wine regions requires a
      knowledge of the spatial variation in temperature, which is also used to assess
      different grapevine cultivars and to delimit appropriate zones for winegrape
      production. However, usually temperature data and methods applied to properly
      delineate homogeneous areas are not adequate to generate accurate maps.With the
      aim of providing an analysis using four temperature-based indices, quantifying
      their spatial variability, and representing the spatial pattern of each index
      throughout Extremadura, one of the most important Spanish wine regions,
      temperature data from 117 meteorological stations, considering the 1980-2011
      period, were utilized. The statistical properties of each index were assessed
      and, later, they were mapped by means of an integrated geographic information
      system (GIS) and a multivariate geostatistics (regression-kriging) approach.
      Results show that heat-sum temperature indices were highly related to the more
      simple growing season temperature; however, temperature regime differences varied
      upon which index was employed. The spatial variability of climate within
      Extremaduran natural regions (NR) is significant; although the warmer conditions
      predominate, some NR have part of their territory by up to eight climate classes.
      This information enables a better understanding of the viticulture suitability
      within each NR and delineating homogeneous zones. The use of consistent
      bioclimatic indices and an advanced geostatistical algorithm have made it
      possible to delimit and compare within-region climates and also enabled
      comparisons of Extremaduran NR with others worlwide, which should be taken into
      account to select varieties and assess the possibilities of producing new wines.

PMID- 24659116
TI  - Special Issue, Phenology 2012 Conference, Milwaukee, WI, USA.

PMID- 24659117
TI  - Transjugular melody valve placement in a small child with protein losing
      enteropathy.
AB  - The authors present a patient with situs inversus totalis, dextrocardia, and
      tetralogy of Fallot with complete AV canal who underwent pulmonary valve-sparing
      complete repair during infancy but developed progressive pulmonary outflow
      obstruction on serial follow-up. His right ventricular outflow tract (RVOT) was
      prestented as a precursor for Melody valve placement. After this, he developed
      protein losing enteropathy (PLE) which was unresponsive to medical management.
      Finally, he received transcatheter Melody valve percutaneously in the pulmonic
      position that lead to clinical and biochemical resolution of his PLE symptoms.

PMID- 24659118
TI  - Anti-cyclic citrullinated peptide antibody and rheumatoid factor isotypes in
      Iranian patients with rheumatoid arthritis: evaluation of clinical value and
      association with disease activity.
AB  - In this study we determined the frequency, sensitivity and specificity of anti
      cyclic citrullinated peptides (anti-CCP) IgG antibody, total rheumatoid factor
      (RF-T), and RF isotypes in Iranian patients with rheumatoid arthritis (RA) and
      their association with age, clinical and serological parameters. Anti-CCP and RF
      T and RF isotypes level were measured in 418 patients and 399 healthy controls by
      enzyme-linked immunosurbant assay (ELISA). Additionally, serum C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) and
      disease activity score (DAS28) were evaluated in RA patients. The anti-CCP was
      positive in 53.1% of RA patients and 4.7% of controls. The frequency of RF-T was
      61.87% and 17.66% in RA patients and controls respectively. The prevalence of RF
      isotypes in RA patients was 46.52% for RF-IgM, 23.47% for RF-IgA and 21.74% for
      RF-IgG. 31.39% of RA patients were RF-IgM positive without RF-IgA and RF-IgG and
      21.9% were positive for all three RF classes. The anti-CCP positive patients
      showed increased number of swollen joints. On the other hand, RF-T positive
      patients exhibited a longer disease duration, lower age of onset and also higher
      ESR, CRP level and increased swollen joints. RF-T titer was significantly higher
      in RA patients with active disease compared to remission, low and moderate active
      groups. The sensitivity and specificity were 53.1, 95.3 for anti-CCP antibody and
      61.8, 82.3 for RF-T. Our results support that anti-CCP and RF titer maybe
      valuable in estimation of disease activity and other inflammatory parameters in
      RA patients.

PMID- 24659119
TI  - Altered pattern of Naive and memory B cells and B1 cells in patients with chronic
      granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder
      characterized by a greatly increased susceptibility to severe fungal and
      bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We
      aimed to investigate immunophenotype alterations of naive and memory B cells and
      B1a cells in peripheral whole blood from Iranian patients with CGD. Flow
      cytometric analysis was performed on peripheral blood samples from 31 CGD
      patients and 23 healthy controls (HC) to study naive (IgD+/CD27-), memory (CD27+)
      B and B1a (CD5+) cells. Soluble CD27 (sCD27) and immunoglobulins were also
      measured by ELISA and the nephelometric method, respectively. We found
      significantly higher levels of naive B cells and B1a cells but lower levels of
      memory B cells in CGD patients compared to HC.. There was no significant
      difference in soluble CD27 (sCD27) alteration between CGD patients and HC. Our
      findings suggested a role for NADPH oxidase in process of B cell differentiation
      and impairing conversion of naive B cells to memory B cells and altered B1a cells
      in CGD patients. Increased susceptibility of CGD patients to opportunistic
      infections and autoimmune disorders could be partly explained by the altered
      phenotype of B lymphocytes in these patients. 

PMID- 24659120
TI  - Otological findings in pediatric patients with hypogammaglobulinemia.
AB  - The main clinical presentation of patients with primary antibody deficiency (PAD)
      incorporates upper respiratory tract infections comprising otitis media,
      sinusitis and pneumonia. This study was designed to investigate clinical and
      paraclinical otological complications in major types of PAD. A cross sectional
      study was conducted on 55 PAD patients with diagnosis of selective IgA
      deficiency, common variable immunodeficiency (CVID), X-linked agammaglobulinemia
      (XLA), and hyper IgM syndrome. All patients underwent otological examinations,
      audiometry, and auditory brain stem response. Otological complications were
      detected in 54.5% of PAD patients. Conductive hearing loss was the main finding
      amongst PID patients (73.3%) followed by sensorineural hearing loss which was
      present in 8 cases. Otitis media with effusion (21.8%), chronic otitis media
      (27.2%), tympanosclerosis with intact tympanic membrane (5.4%) and auditory
      neuropathy (3.6%) were most important found complications. CVID and XLA patients
      with prophylactic usage of antibiotics had lower rate of audiological
      complications (p=0.04) and otitis media with effusion (p=0.027). As our results
      showed, asymptomatic otological findings were not rare in PAD patients;
      therefore, a systematic otological investigation is recommended as an integral
      part of the management and follow-up of these patients. 

PMID- 24659121
TI  - The effect of conventional immunosuppressive therapy on cytokine serum levels in
      pemphigus vulgaris patients.
AB  - Pemphigus vulgaris is an autoimmune disease, in which the role of Th17 cytokines
      needs to be further explored. This study was performed to assess serum levels of
      three interleukins (IL) required for Th17 differentiation (IL-1beta, IL-6 and IL
      23) and two specific Th17 cytokines (IL-17 and IL-22) in a group of patients with
      pemphigus vulgaris, at baseline, 3 weeks and 6 months after treatment.
      Correlations between anti-desmogleins and cytokines with disease severity as well
      as the influence of therapy on the above factors were assessed. Forty-three first
      admitted pemphigus vulgaris patients with the active disease entered the study,
      but only 31 completed the study. Forty-five healthy volunteers were recruited as
      a control group. The patients were treated with conventional immunosuppressive
      therapy (oral prednisolone and azathioprine). Cytokines and anti-desmogleins were
      measured, using enzyme-linked immunosorbent assay. General linear model was used
      to evaluate the changes over time. In patients at baseline, mean serum level of
      IL-6 was higher, while mean levels of IL-1beta and IL-22 were lower than the
      controls. After 3 weeks of therapy, IL-1beta and IL-6 levels showed a decreasing
      trend, whereas IL-22 showed an increasing trend. Mean anti-desmogleins 1 and 3
      values decreased significantly during the time. Anti-desmoglein values were
      significantly correlated with disease severity. In conclusion, IL-1beta and IL-6
      could be involved in the pathogenesis of pemphigus vulgaris. The positive trend
      of IL-22 is a new finding and should be confirmed by further studies. 

PMID- 24659122
TI  - Interferon-gamma gene polymorphism +874 (a/t) in Chinese children with Henoch
      Schonlein purpura.
AB  - The aim of this study was to investigate the possible influence of Interferon
      gamma (IFN-gamma) gene polymorphism +874 (A/T) (rs2430561) in the susceptibility
      and renal complications of patients with Henoch-Schonlein purpura (HSP). We also
      studied the effects of IFN-gamma allelic variation on serum levels of pro-and
      anti-inflammatory cytokines in HSP patients. The study population comprised 97
      patients suffering from HSP and 97 control participants. Patients and controls
      were genotyped for a single nucleotide polymorphism +874 (A/T) in the first
      intron of the IFN-gamma gene by the TaqMan PCR method. Frequencies of individuals
      with IFN-gamma +874 AA, AT and TT genotypes were 77.3%, 21.6% and 1% in HSP
      patients and 79.4%, 17.5% and 3.1% in controls, respectively. The frequency of
      the AA genotype in HSP patients with nephritis was slightly higher (83.3%) than
      in HSP patients without nephritis (73.8%). The allele A occurred more commonly in
      HSP patients with nephritis (92%) than in HSP patients without nephritis (86%),
      but these differences were not statistically significant (p= 0.469 and p= 0.244,
      respectively). In addition, significant difference in serum IL-10 levels between
      IFN-gamma +874 different genotype groups was found. Our results do not support a
      role for IFN-gamma gene polymorphism +874 (A/T) in the susceptibility to HSP and
      allelic variation at IFN-gamma +874 locus had no effect on serum levels of
      cytokines in patients with HSP except for IL-10. 

PMID- 24659123
TI  - Evaluation of the correlation and reproducibility between histamine, IL-4, and IL
      13 release from human basophils.
AB  - Human basophils play a key role in allergic diseases such as asthma and in a
      variety of immunological disorders. The generation of IL-4 and IL-13 can be
      induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and
      stimulus-dependent differences in the regulation of these cytokines could have
      relevance to their biological effects. The aim of the present study was
      activation of basophils in order to evaluate the extent of histamine, IL-4, and
      IL-13 generations. Basophil-enriched suspensions were prepared by Percoll
      gradients. The release of histamine and cytokines was assessed after activation
      with either anti-human IgE (1/1000 or 1/10000, 4 h or 24 h) or IL-3 (100 ng/ ml,
      24 h). Results were analysed statistically, using ANOVA test. Using anti-IgE,
      there was no significant correlation between the extent of either IL-4 (r=0.24,
      p=0.35) or IL-13 (r=0.47, p=0.098) and histamine release. Using IL-3 as
      stimulator, results showed that the extent of IL-13 correlated with histamine
      release(r=0.44, p=0.036). There was no correlation between the extent of IL-4 and
      the degree of either histamine (r=0.077, p=0.72) or IL-13 (r=0.162, p=0.5). The
      reproducibility of cytokines isolated from the same donor (on different
      occasions) indicated that the ability of anti-IgE to induce cytokines was
      consistently similar for a given donor. Our data showed that the pathways leading
      to IL-3-triggering histamine release and IL-13 generation show similarity. Donor
      dependent differences may be responsible for this wide range in the extent of
      releasibility. The ability of IL-3 to release cytokines from basophils showed a
      wider range. 

PMID- 24659124
TI  - Effects of imatinib mesylate in mouse models of multiple sclerosis and in vitro
      determinants.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple
      sclerosis (MS), This autoimmune disease is mainly mediated by adaptive and innate
      immune responses that lead to an inflammatory demyelination and axonal damage.
      Imatinib mesylate is a selective protein tyrosine kinase inhibitor with
      immunomodulatory properties that abrogates multiple signal transduction pathways
      in immune cells. In the present research, our aim was to test the therapeutic
      efficacy of imatinib in experimental model of MS. We performed EAE induction in
      23 female C57 mice by myelin oligodendrocyte glycoprotein-35-55 (MOG35-55) in
      Complete Freund's Adjuvant (CFA) emulsion and used imatinib for treatment of EAE.
      The clinical evaluation and histopathology were assessed. Also for in vitro
      analysis, we used U-87 MG, C6 and WEHI-164 cell lines to evaluate the inhibitory
      effects of imatinib in cell proliferation, as well as pro-inflammatory cytokines
      (TNF-alpha, IL-1beta, IL-6) and matrix metalloproteinase (MMP) secretion. Our
      findings demonstrated that this drug had beneficial effects on EAE by attenuation
      in the severity and a delay in the onset of disease. In vitro, imatinib inhibited
      cell proliferation, MMP-2 expression and activity and also attenuated the
      production of proinflammatory cytokines. Imatinib with its potential therapeutic
      effects and immunomodulatory properties may be considered, after additional
      necessary tests and trials, for treatment of MS. 

PMID- 24659125
TI  - HLA-G allele and haplotype frequencies in a healthy population of Iran.
AB  - The human leukocyte antigen (HLA)-G molecule is expressed in cytotrophoblast
      cells, adult thymic epithelial cells, erythroblasts, pancreatic islets and
      mesenchymal stem cells. Although, HLA-G expression in allotransplanted patients
      is correlated with a better allograft acceptance, it is associated with an
      advanced grade of the tumor in cancer. In addition to the role on the immune
      system, HLA-G is also involved in successful pregnancy through the embryo
      implantation, fetal survival and the initial steps of hematopoiesis and
      angiogenesis. The aim of this study was determination of HLA-G allele frequencies
      in a healthy population of Iran. In this research, we selected 100 samples from
      healthy Iranian individuals and henceforth, we used polymerase chain reaction
      (PCR) followed by sequencing technique for exon 2, 3, 4 and intron 2 of the gene
      for evaluating the HLA-G alleles frequencies. Investigation of intronic (intron
      2) variation is the novelty of our study. The obtained results indicated thirteen
      alleles of HLA-G in Iranian individuals including G*01:01:01:01, G*01:06,
      G*01:01:01:06, G*01:01:02, G*01:01:03, G*01:01:05, G*01:01:06, G*01:01:07,
      G*01:01:08, G*01:03, G*01:04:01, G*01:04:03, and G*01:04:04. According to this
      study, the most prevalent alleles in the Iranian population were G*01:01:01:01
      (52.5%), G*01:01:02 (16%) and G*01:04:03 (14.5%) and also the lowest alleles
      regarding the frequency were G*01:01:01:06 (0.5%) and G*01:03 (0.5%). The results
      of G*01:01:01:01 and G*01:04:01 frequencies showed some similarities with the
      polish population. Our results were similar to the north Indian population for
      the frequencies of G*01:06 and G*01:01:02. 

PMID- 24659126
TI  - A patch test confirmed phenobarbital-induced fixed drug eruption in a child.
AB  - A-10-year-old girl was referred to our department for multiple hyperpigmented
      plaques. One week previously, she had been given one suppository of
      acetylsalicylic acid - phenobarbital for fever. Twelve hours after the drug
      intake the child developed pruritic red plaques on the left thigh. Six weeks
      after resolution of the acute reaction, patch tests were performed separately,
      with phenobarbital and acetylsalicylic acid. On 48-hour reading, only the
      phenobarbital patch test on residual pigmented lesion was positive. Because of
      possible cross-reactions between aromatic anticonvulsants, subsequent patch tests
      using carbamazepine and phenytoin on residual pigmented lesions were performed.
      They were all negative at 48-hour reading. To our knowledge, only two isolated
      pediatric cases of Phenobarbital-induced FDE have been reported in the
      literature. In this case report, as it was difficult to determine whether
      phenobarbital or acetylsalicylic acid was responsible for this reaction,
      subsequent patch tests allowed the identification of the culprit component since
      it was positive to phenobarbital. 

PMID- 24659127
TI  - Significance of immunostaining data in IgA nephropathy patients; current
      knowledge and new concepts.

PMID- 24659130
TI  - Switching from high-dose clopidogrel to prasugrel in ACS patients undergoing PCI:
      a single-center experience.
AB  - Prasugrel has been shown to be superior to clopidogrel in the setting of ACS
      patients undergoing coronary angioplasty. However, few data have been reported so
      far on those patients who switch from clopidogrel to prasugrel after coronary
      angioplasty. Aim of the current study was to evaluate the safety of prasugrel
      loading dose administration in ACS patients undergoing PCI and pretreated with
      high-dose clopidogrel. From May 2010 to December 2011 150 ACS patients undergoing
      coronary angioplasty and pretreated with high-dose clopidogrel, were switched to
      prasugrel loading dose soon after the procedure. They were matched (ratio 1:2)
      according to sex and age with a group of 300 ACS patients undergoing angioplasty
      and treated with high-dose clopidogrel only from May 2010 to December 2011. All
      demographic clinical and angiographic were collected. Primary endpoint was the
      rate of major bleeding complications (according to ACUITY trial definition) at 30
      day follow-up. Secondary endpoints were: TIMI major and minor bleeding, definite
      stent thrombosis, major adverse cardiac events (MACE) and Net adverse cardiac
      events (NACE) at 30-day followup. The two groups of patients showed similar
      baseline demographic, and clinical characteristics. Most of the patients had
      unstable angina or non-ST segment elevation myocardial infarction. Almost (about
      95 %) all patients underwent radial approach. No difference was observed in major
      bleeding complications according to both ACUITY (2.0 vs 2.0 %) and TIMI Major
      (0.7 vs 1.3 %) definition. No difference between the two groups was observed in
      terms of in-stent thrombosis, MACE and NACE at 30-day follow-up. Our
      observational study showed that switching to prasugrel with loading dose soon
      after angioplasty among ACS patients who were pretreated with clopidogrel seems
      to be well tolerated without overt evidence of heightened major bleeding. Future
      large randomized trials are certainly needed to confirm these findings.

PMID- 24659129
TI  - Losartan prevents acquired epilepsy via TGF-beta signaling suppression.
AB  - OBJECTIVE: Acquired epilepsy is frequently associated with structural lesions
      after trauma, stroke, and infections. Although seizures are often difficult to
      treat, there is no clinically applicable strategy to prevent the development of
      epilepsy in patients at risk. We have recently shown that vascular injury is
      associated with activation of albumin-mediated transforming growth factor beta
      (TGF-beta) signaling, and followed by local inflammatory response and
      epileptiform activity ex vivo. Here we investigated albumin-mediated TGF-beta
      signaling and tested the efficacy of blocking the TGF-beta pathway in preventing
      epilepsy. METHODS: We addressed the role of TGF-beta signaling in epileptogenesis
      in 2 different rat models of vascular injury, combining in vitro and in vivo
      biochemical assays, gene expression, and magnetic resonance and direct optical
      imaging for blood-brain barrier permeability and vascular reactivity. Long-term
      electrocorticographic recordings were acquired in freely behaving animals.
      RESULTS: We demonstrate that serum-derived albumin preferentially induces
      activation of the activin receptor-like kinase 5 pathway of TGF-beta receptor I
      in astrocytes. We further show that the angiotensin II type 1 receptor
      antagonist, losartan, previously identified as a blocker of peripheral TGF-beta
      signaling, effectively blocks albumin-induced TGF-beta activation in the brain.
      Most importantly, losartan prevents the development of delayed recurrent
      spontaneous seizures, an effect that persists weeks after drug withdrawal.
      INTERPRETATION: TGF-beta signaling, activated in astrocytes by serum-derived
      albumin, is involved in epileptogenesis. We propose losartan, a drug approved by
      the US Food and Drug Administration, as an efficient antiepileptogenic therapy
      for epilepsy associated with vascular injury.

PMID- 24659131
TI  - Switching from clopidogrel to prasugrel in patients having coronary stent
      implantation.
AB  - There are very few clinical data concerning the safety of switching from
      clopidogrel to prasugrel in patients undergoing coronary stenting. However, in
      the daily activity, clinicians face the decision of switching patients at high
      risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to
      evaluate clinical events in patients undergoing coronary stent implantation and
      prasugrel therapy with (SWITCH group) or without (NAIVE group) prior clopidogrel
      therapy. A total of 454 patients with stable or unstable coronary artery disease,
      aged 70 +/- 10 years, underwent non-emergent stent implantation and received
      prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before
      switching to prasugrel therapy. In 239 patients with high residual platelet
      reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from
      72 +/- 11 to 43 +/- 16 % (p < 0.001). There was no difference in in-hospital
      major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and
      NAIVE groups as well as in mortality, acute stent thrombosis, reinfarction and
      stroke rates. At multivariable analysis, independent predictors of bleeding were
      female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27
      [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed
      after switching propensity score adjustment (c-statistic 0.81; Hosmer-Lemeshow
      test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non
      emergent coronary stent implantation seems to be tolerated with no overt signs of
      increased bleeding.

PMID- 24659132
TI  - A descriptive study of symptom change as a function of attachment and emotion
      regulation in a naturalistic adolescent inpatient setting.
AB  - This is the first study to describe the relation between attachment security,
      emotion regulation, and symptom change in a sample of adolescents completing
      inpatient treatment in a naturalistic setting. We examined whether attachment
      security predicted symptom change, and whether emotion regulation capacities
      mediated this relation. A sample of n = 194 inpatient adolescents was assessed
      (65.5 % female, Mage = 15.45 years, SD = 1.44) at admission and discharge and
      analyses were conducted in accordance with the aforementioned objectives
      including testing of moderation and mediation models. We found that securely
      attached adolescents experienced greater reduction in internalizing symptoms from
      admission to discharge, even when controlling for length of stay. Nonacceptance
      of emotional responses mediated the relation between maternal attachment security
      and internalizing symptom change. These findings did not hold for externalizing
      symptoms, nor when paternal attachment was explored. Attachment plays an
      important role in symptom change for internalizing problems, with nonacceptance
      of emotional responses partially mediating this link. Possible explanations for
      the absence of moderation for paternal attachment and externalizing problems are
      discussed, as are explanations for the mediating effect of emotion regulation.

PMID- 24659133
TI  - Anxiety disorders and behavioral inhibition in preschool children: a population
      based study.
AB  - This study assessed the prevalence of anxiety disorders in preschool children and
      their associations with behavioral inhibition as a temperamental precursor. A
      representative sample of 1,342 children aged 4-7 years (M = 6;1, SD = 4.80) was
      examined with a standardized parental questionnaire, including items referring to
      anxiety disorders at the current age and behavioral inhibition at the age of 2
      years. The total prevalence of anxiety disorders was 22.2 %. Separation anxiety
      (SAD) affected 7 %, social phobia (SOC) 10.7 %, specific phobia (PHOB) 9.8 % and
      depression/generalized anxiety (MDD/GAD) 3.4 % of children. The prevalence of
      most types of anxiety was higher in girls except for separation anxiety, which
      affected more boys. Behavioral inhibition in the second year of life was
      associated with all types of anxiety. Anxiety disorders are common but frequently
      overlooked in preschool children. Different subtypes can be differentiated and
      are often preceded by behavioral inhibition. Assessment, prevention and treatment
      of anxiety disorders are recommended in preschool children.

PMID- 24659135
TI  - A case of CD138-/CD19+/CD4+ IgD plasma cell leukemia.
AB  - Background: Plasma cell leukemia (PCL) is an uncommon and aggressive disease
      caused by the clonal proliferation of atypical plasma cells with phenotypical
      abnormalities similar to those seen in multiple myeloma (MM), although at
      different rates. Here we report a case of IgD PCL with a very unusual CD138
      /CD19+/CD4+ phenotype Methods: Peripheral blood and bone marrow samples from a 37
      year old patient afflicted by an aggressive plasma cell dyscrasia were examined
      and analyzed by conventional morphology, flow cytometry and immunohistochemistry.
      Results: Analysis of peripheral blood fulfilled criteria for PCL (more than 20%
      and more than 2x10e9 cells/L). However, flow cytometry and immunohistochemistry
      phenotyping revealed that the cells were CD138-/CD38+/CD19+/CD4+/CD56-/CD117-
      Conclusion: PCL is diagnosed on peripheral blood smear. Immunophenotyping is a
      tool that can be helpful in diagnosing difficult cases but its atypical findings
      should not prevent the appropriate PCL diagnosis in clinically and
      morphologically unquestionable cases. (c) 2014 Clinical Cytometry Society.

PMID- 24659136
TI  - Successful treatment of refractory chylothorax by pedicled omentoplasty.
AB  - A 52-year-old female with a history of past surgery for arteriovenous
      malformation of the thoracic spinal cord presented with left chylothorax.
      Lymphangiography identified diffuse lymphatic vessel (LV) growth with ectasia at
      the left supradiaphragmatic level. On the right side, the LVs were absent due to
      previous surgery. Given the ineffectiveness of conservative management, the
      patient required surgery. Thoracotomy showed extensive pleural fibrosis, lung
      atelectasis, and diffuse chyle defluxion on the parietal pleura. The diffuse
      chyle defluxion was not resolved by ligation. Therefore, we performed pedicled
      omentoplasty to fill the pleural space and to utilize its drainage and angiogenic
      capacity. Two years after the procedure, there was no sign of relapse. There are
      very few reports of refractory chylothorax successfully treated by pedicled
      omentoplasty. The procedure would be useful for the treatment of chylothorax when
      non-surgical or typical surgical management fails.

PMID- 24659134
TI  - A high-resolution study of hippocampal and medial temporal lobe correlates of
      spatial context and prospective overlapping route memory.
AB  - When navigating our world we often first plan or retrieve an ideal route to our
      goal, avoiding alternative paths that lead to other destinations. The medial
      temporal lobe (MTL) has been implicated in processing contextual information,
      sequence memory, and uniquely retrieving routes that overlap or "cross paths."
      However, the identity of subregions of the hippocampus and neighboring cortex
      that support these functions in humans remains unclear. The present study used
      high-resolution functional magnetic resonance imaging (hr-fMRI) in humans to test
      whether the CA3/DG hippocampal subfield and parahippocampal cortex are important
      for processing spatial context and route retrieval, and whether the CA1 subfield
      facilitates prospective planning of mazes that must be distinguished from
      alternative overlapping routes. During hr-fMRI scanning, participants navigated
      virtual mazes that were well-learned from prior training while also learning new
      mazes. Some routes learned during scanning shared hallways with those learned
      during pre-scan training, requiring participants to select between alternative
      paths. Critically, each maze began with a distinct spatial contextual Cue period.
      Our analysis targeted activity from the Cue period, during which participants
      identified the current navigational episode, facilitating retrieval of upcoming
      route components and distinguishing mazes that overlap. Results demonstrated that
      multiple MTL regions were predominantly active for the contextual Cue period of
      the task, with specific regions of CA3/DG, parahippocampal cortex, and perirhinal
      cortex being consistently recruited across trials for Cue periods of both novel
      and familiar mazes. During early trials of the task, both CA3/DG and CA1 were
      more active for overlapping than non-overlapping Cue periods. Trial-by-trial Cue
      period responses in CA1 tracked subsequent overlapping maze performance across
      runs. Together, our findings provide novel insight into the contributions of MTL
      subfields to processing spatial context and route retrieval, and support a
      prominent role for CA1 in distinguishing overlapping episodes during navigational
      "look-ahead" periods.

PMID- 24659137
TI  - Sliding external fixator "a product design and cadaveric experiment".
AB  - BACKGROUND: External fixation spanning a joint like the elbow, while maintaining
      joint mobility, is a well-established practice, and it could be done with a
      variety of external fixation systems. In current systems, correct identification
      of the elbow center of rotation under X-ray guidance with lateral views is
      mandatory. If the center of rotation of the fixator is not aligned with that of
      the elbow joint, the assembly will not work. This new design idea aims to
      propagate the principle of sliding external fixation applied on the extensor side
      of a joint, with the limbs of the fixator being able to slide in and out during
      joint extension and flexion, respectively, without hindering the joint movement,
      without the need to use X-ray guidance to identify the center of rotation.
      MATERIALS AND METHODS: A cadaveric experiment was carried on using a sliding
      fixator prototype applies on two cadaveric elbow specimens, which were tested
      though the arc of movement. RESULTS: Assembling the fixator over the intact
      elbows without identifying the center of rotation did not impede the joint
      movement. Furthermore, after surgical dislocation of the elbow, the external
      fixator was able to keep the joint congruent, throughout the movement arc.
      CONCLUSION: It was possible to apply a sliding external fixator on the extensor
      surface of a joint without identifying the center of rotation, and that does not
      seem to impede the joint movement, while can still keep the dislocated joint
      congruent despite attempted distraction.

PMID- 24659138
TI  - Genistein alleviates radiation-induced pneumonitis by depressing Ape1/Ref-1
      expression to down-regulate inflammatory cytokines.
AB  - The aim of the study was to investigate the role of genistein in alleviating
      radiation-induced pneumonitis(RIP) through down-regulating levels of the
      inflammatory cytokines by inhibiting the expression of apurinic/apyrimidinic
      endonuclease 1/redox factor-1 (Ape1/Ref-1). Fifty female C57BL/6J mice (8 weeks
      old) were randomly divided into a control group, a pure irradiation (IR) group
      and a genistein + IR group. At the four time points after IR, hematoxylin, and
      Masson's trichrome stainings were used to examine the pathological changes and
      collagen fiber deposition. Flow cytometry was used to detect reactive oxygen
      system (ROS) changes, EMSA was used to estimate the nuclear factor kappa B (NF
      kappaB) transcriptional activities and an ELISA assay was used to measure the
      levels of TGF-beta1, IL-1beta, TNF-alpha, and IL-6 in the serum and
      bronchoalveolar lavage fluid (BALF) 2 weeks after IR.The pathological detection
      results showed acute inflammatory/fibrinoid exudation of the thoracic tissue
      after IR,which was significantly alleviated with genistein. The IR inducedan APE1
      protein expression increase and NF-jB was effectively suppressed by genistein (P
      < 0.05). The induction of the inflammatory cytokines TGF-beta1, IL-1beta,TNF
      alpha, and IL-6 by IR were in turn inhibited in the serum and BALF of the
      genistein-pretreated mice (P < 0.05). In addition, the ROS production was
      significantly boosted in the A549 cells after IR, which could be down-regulated
      by the pretreatment of genistein. The results demonstrate that genistein
      alleviates RIP by attenuating the inflammatory response in the initiation of RIP.
      A possible target of genistein is the Ape1/ref-1, which regulates key
      inflammatory cytokines by activating the NF-kappaB.

PMID- 24659139
TI  - The effects of hispidulin on bupivacaine-induced neurotoxicity: role of AMPK
      signaling pathway.
AB  - Bupivacaine is a sodium channel blocker, which is widely used for local
      infiltration nerve block, epidural and intrathecal anesthesia. However,
      bupivacaine could cause nerve damage. Hispidulin was shown to be able to
      penetrate the blood-brain barrier and possess antiepileptic activity. In this
      study, we investigate whether hispidulin administration could attenuate
      bupivacaine-induced neurotoxicity. Bupivacaine-challenged mouse neuroblastoma N2a
      cells were treated with hispidulin. The neuron injury was assessed by examination
      of cell viability and apoptosis. The levels of activation of AMP-activated
      protein kinase (AMPK) signaling pathway were examined along with the effect of
      blocking AMPK signaling on cell viability in the presence of hispidulin and
      bupivacaine. Our results showed that Bupivacaine treatment significantly
      decreased cell viability and induced apoptosis. Treatment with hispidulin
      significantly attenuated bupivacaine-induced cell injury. In addition, hispidulin
      treatment increased the levels of phospho-AMPK and phospho-GSK3beta and
      attenuated bupivacaine-induced loss in mitochondrial membrane potential.
      Furthermore, we found that blocking AMPK signaling pathway significantly
      abolished the cytoprotective effect of hispidulin against bupivacaine-induced
      cell injury. Our findings suggest that treatment of neuroblastoma cells with
      hispidulin-protected neural cells from Bupivacaine-induced injury via the
      activation of the AMPK/GSK3beta signaling pathway.

PMID- 24659140
TI  - Treadmill gait training improves baroreflex sensitivity in Parkinson's disease.
AB  - BACKGROUND: Partial weight supported treadmill gait training (PWSTT) is widely
      used in rehabilitation of gait in patient with Parkinson's Diseases (PD).
      However, its effect on blood pressure variability (BPV) and baroreflex
      sensitivity (BRS) in PD has not been studied. AIM: To evaluate the effect of
      conventional and treadmill gait training on BPV components and BRS. METHODS:
      Sixty patients with idiopathic PD were randomized into three groups. Twenty
      patients in control group were on only stable medication, 20 patients in
      conventional gait training (CGT) group (Stable medication with CGT) and 20
      patients in PWSTT group (Stable medication with 20 % PWSTT). The CGT and PWSTT
      sessions were given for 30 min per day, 4 days per week, for 4 weeks (16
      sessions). Groups were evaluated in their best 'ON' states. The beat-to-beat
      finger blood pressure (BP) was recorded for 10 min using a Finometer instrument
      (Finapres Medical Systems, The Netherlands). BPV and BRS results were derived
      from artifact-free 5-min segments using Nevrocard software. RESULTS: BRS showed a
      significant group with time interaction (F = 6.930; p = 0.003). Post-hoc analysis
      revealed that PWSTT group showed significant improvement in BRS (p < 0.001) after
      4 weeks of training. No significant differences found in BPV parameters; systolic
      BP, diastolic BP, co-variance of systolic BP and low frequency component of
      systolic BP. CONCLUSIONS: Four weeks of PWSTT significantly improves BRS in
      patients with PD. It can be considered as a non-invasive method of influencing
      BRS for prevention of orthostatic BP fall in patients with PD.

PMID- 24659141
TI  - Evidence that the central canal lining of the spinal cord contributes to
      oligodendrogenesis during postnatal development and adulthood in intact rats.
AB  - Two waves of oligodendrogenesis in the ventricular zone of the spinal cord (SC
      VZ) during rat development, which take place between embryonic days 14 and 18
      (E14-E18) and E20-E21, have been described. In the VZ of the brain, unlike the SC
      VZ, a third wave of oligodendrogenesis occurs during the first weeks of postnatal
      development. Using immunofluorescence staining of intact rat SC tissue, we
      noticed the presence of small numbers of Olig2(+) /Sox-10(+) cells inside the
      lining of the central canal (CC) during postnatal development and adulthood.
      Olig2(+) /Sox-10(+) cells appeared inside the lining of the CC shortly after
      birth, and their number reached a maximum of approximately 0.65 +/- 0.14 cell/40
      MUm section during the second postnatal week. After the latter development, the
      number of Olig2(+) /Sox-10(+) cells decreased to 0.21 +/- 0.07 (P36) and 0.18 +/-
      0.1 cell/section (P120). At P21, Olig2(+) /Sox-10(+) cells inside the CC lining
      started to express other oligodendroglial markers such as CNPase, RIP, and APC.
      Olig2(+) /Sox-10(+) cells usually did not proliferate inside the CC lining and
      were only rarely found to be immunoreactive against oligodendrocyte progenitor
      markers such as NG2 or PDGFRalpha. Using 5-bromo-2-deoxyuridine administration at
      P2, P11, P22, or P120-P125, we revealed that these cells arose in the CC lining
      during postnatal development and adulthood. Our findings confirmed that the CC
      lining is the source of a small number of cells with an oligodendroglial
      phenotype during postnatal development and adulthood in the SC of intact rats.

PMID- 24659142
TI  - Clinical relevance of plasma miR-21 in new-onset systemic lupus erythematosus
      patients.
AB  - BACKGROUND: Plasma miR-21 is widely investigated as biomarker in many diseases.
      Recent studies show that miR-21 participates in the development of systemic lupus
      erythematosus (SLE). The aim of this study was to evaluate the expression profile
      of miR-21 in the plasma of SLE patients. METHODS: Relative quantities of plasma
      miR-21 both in SLE patients and healthy controls were determined by relative qRT
      PCR under endogenous and exogenous controls. The diagnostic value of plasma miR
      21 was evaluated in SLE patients. Data of some SLE-associated clinical parameters
      were collected. RESULTS: Eighty participants from Central China were recruited.
      Forty-four participants were new-onset SLE patients and the others were healthy
      controls. Plasma miR-21 level in SLE patients was higher than that of healthy
      controls (P = 0.031). Receiver operating characteristic analysis of plasma miR-21
      revealed an Area Under Curve (AUC) of 0.64 +/- 0.06 (95% CI: 0.51-0.76, P =
      0.03854) when differentiating SLE from healthy controls. The level of plasma miR
      21 was not associated with the level of white blood cells (P = 0.4284), red blood
      cells (P = 0.4079), and platelets (P = 0.4961), but significantly correlated with
      the level of plasma complement C3 (r = -0.5297, P = 0.0004), C4 (r = -0.4732, P =
      0.0020), and serum uric acid (r = 0.3932, P = 0.0121) in SLE patients.
      CONCLUSIONS: Plasma miR-21 in SLE patients from Central China is overexpressed.
      Since circulating miR-21 is aberrantly expressed in many diseases, the applying
      of it as a disease biomarker should be considered carefully.

PMID- 24659143
TI  - Extraction of site-site bridge functions and effective pair potentials from
      simulations of polar molecular liquids.
AB  - We develop an efficient method to extract site-site bridge functions from
      molecular simulations. The method is based on the inverse solution of the
      reference site interaction model. Using the exact long-range asymptotics of site
      site direct correlation functions defined by the site-site Ornstein-Zernike
      equations, we regularize the ill-posed inverse problem, and then calculate site
      site bridge functions and effective pair potentials for ambient water, methanol,
      and ethanol. We have tested the proposed algorithm and checked its performance.
      Our study has revealed various peculiarities of the site-site bridge functions,
      such as long-range behavior, strong dependence on the electrostatic interactions.
      Using the obtained data, we have calculated thermodynamic properties of the
      solvents, namely, isothermal compressibility, internal energy, and Kirkwood-Buff
      integrals. The obtained values are in excellent agreement not only with molecular
      simulations but also with available experimental data. Further extensions of the
      method are discussed.

PMID- 24659144
TI  - An atypical case of tularemia presented with pseudoptosis.
AB  - We report an unusual case of tularemia involving pseudoptosis associated with
      deterioration of the lymphatic drainage system extending from the upper eyelid to
      the preauricular lymph nodes. A 16-week pregnant patient was admitted with an
      absess on the neck, preauricular lymphadenopathy, and pseudoptosis on the left
      side. The micro-agglutination test was positive for Francisella tularensis
      antibody at a titer of 1/200. The absess was surgically drained and oral
      cefuroxime was given for 6 weeks. Two weeks after drainage, the pseudoptosis
      improved due to the recovery of lymphatic drainage system of the eyelid and
      remission of the absess on the neck. Our case report contributes to the medical
      literature on tularemia during pregnancy and informs healthcare professionals on
      the management of the infection in such cases.

PMID- 24659145
TI  - Predicting vascular complications during transfemoral transcatheter aortic valve
      replacement using computed tomography: a novel area-based index.
AB  - BACKGROUND: Computed tomography (CT) imaging has not been systematically studied
      for predicting vascular complications during transcatheter aortic valve
      replacement (TAVR). METHODS: Clinical data were obtained from the electronic
      medical record and analysis was performed for each individual patient's
      iliofemoral CT angiogram. Sheath : femoral artery diameter ratio (SFAR) and
      sheath : femoral artery area ratio (SFAAR) were defined as the ratio of the
      sheath outer diameter to the femoral minimal lumen diameter (MLD) and sheath area
      to the femoral minimal lumen area (MLA), respectively. RESULTS: A total of 255
      patients underwent TF-TAVR with a 30-day mortality of 0.4% and 30-day stroke rate
      of 1.6%. Twenty-eight (11%) patients suffered a vascular complication, the
      majority of whom (82%) were managed percutaneously. Receiver operating
      characteristic (ROC) curve analysis demonstrated an SFAAR of 1.35 to predict the
      occurrence of vascular complications with a sensitivity of 78.6%. By comparison,
      similar analysis using SFAR provided a value of 1.45 with sensitivity of 64.2%.
      Multivariable modeling confirmed SFAR [OR (95% CI): 8.3(1.8-39.1)] and log
      transformed SFAAR [OR (95% CI): 40.1 (2.4-650.0)] as significant predictors of
      vascular complication. CONCLUSIONS: Using CT analysis, an SFAR of 1.45 and an
      SFAAR of 1.35 are each significant predictors of vascular complications among
      patients undergoing TF-TAVR. Utilization of CT-based area may provide a more
      accurate screen for patients undergoing evaluation for TF-TAVR as it takes into
      consideration the elliptical nature of the vessel. (c) 2014 Wiley Periodicals,
      Inc.

PMID- 24659147
TI  - [Rheumatological healthcare research in an international context].

PMID- 24659146
TI  - Biosignatures in chimney structures and sediment from the Loki's Castle low
      temperature hydrothermal vent field at the Arctic Mid-Ocean Ridge.
AB  - We investigated microbial life preserved in a hydrothermally inactive silica
      barite chimney in comparison with an active barite chimney and sediment from the
      Loki's Castle low-temperature venting area at the Arctic Mid-Ocean Ridge (AMOR)
      using lipid biomarkers. Carbon and sulfur isotopes were used to constrain
      possible metabolic pathways. Multiple sulfur (ddelta34S, Delta33S) isotopes on
      barite over a cross section of the extinct chimney range between 21.1 and 22.5 %
      in delta34S, and between 0.020 and 0.034 % in Delta33S, indicating direct
      precipitation from seawater. Biomarker distributions within two discrete zones of
      this silica-barite chimney indicate a considerable difference in abundance and
      diversity of microorganisms from the chimney exterior to the interior. Lipids in
      the active and inactive chimney barite and sediment were dominated by a range of
      13C-depleted unsaturated and branched fatty acids with delta13C values between 
      39.7 and -26.7 %, indicating the presence of sulfur-oxidizing and sulfate
      reducing bacteria. The majority of lipids (99.5 %) in the extinct chimney
      interior that experienced high temperatures were of archaeal origin. Unusual
      glycerol monoalkyl glycerol tetraethers (GMGT) with 0-4 rings were the dominant
      compounds suggesting the presence of mainly (hyper-) thermophilic archaea.
      Isoprenoid hydrocarbons with delta13C values as low as -46 % also indicated the
      presence of methanogens and possibly methanotrophs.

PMID- 24659148
TI  - [Outpatient rheumatologic treatment in Germany].
AB  - Outpatient rheumatologic treatment in Germany is managed by rheumatologists in
      private practice (n = 557), by authorized rheumatism outpatient centers (n =
      116), by rheumatism centers according to S116b (n = 43) and by university
      outpatient departments. A total number of 975 rheumatologists were registered by
      the end of 2012 of whom approximately 830 were active in outpatient care. With
      this number of rheumatologists Germany is in the middle range in comparison to
      eight industrial nations including the USA. This number is not sufficient to
      provide adequate medical care and the consequences are too long waiting times for
      an appointment with a rheumatologist. Statistical data of the Kassenarztliche
      Bundesvereinigung (KBV, National Association of Statutory Health Insurance
      Physicians) showed 688,000 general insurance patients with rheumatoid arthritis
      (RA). As some 68.9 % of the population are in this insurance scheme there are
      some 770,000 RA patients in Germany (almost 1 % of the population). One way to
      improve rheumatology care in spite of the lack of rheumatologists could be
      special agreements with the general health insurance providers to improve
      cooperation and division of responsibilities between rheumatologists and general
      practitioners, to implement patient education, tighter control and treat to
      target in rheumatology care. Another way could be a new treatment level called
      "ambulant specialist care", with no budget for medical care and no budget for the
      number of patients treated and therefore the chance for rheumatologists to treat
      more patients and have a better income. To achieve that more young doctors
      receive approval as a specialist in rheumatology, more chairs of rheumatology at
      universities and a nationwide stipendium for training assistants are needed. 

PMID- 24659149
TI  - [Inpatient rheumatology treatment in Germany].
AB  - Acute inpatient treatment plays an important role in the care of patients with
      rheumatic diseases in Germany. Inpatient facilities are usually departments in
      general hospitals or highly specialized clinics. The introduction of the
      diagnosis-related groups (DRG) system has led to a change in form which is most
      obviously characterized by more homogeneous structures and shorter hospital
      stays. Many rheumatic patients are, however, treated in general hospitals due to
      a lack of specialized clinics. The presence of a department of rheumatology in
      medical schools is deficient which therefore leads to only a small number of
      specialists in rheumatology. The rheumatologists in inpatient facilities are also
      involved in the care of outpatients, whereby the number of licensed internal
      medical rheumatologists is declining. Further possibilities in outpatient
      treatment in hospitals were created with new governmental regulations (S116b).
      Changes are expected with the implementation of the new outpatient specialist
      medical care (ASV). 

PMID- 24659150
TI  - [Trends in rehabilitation of patients with rheumatic diseases in Germany].
AB  - Recent Deutsche Gesellschaft fur Rheumatologie (DGRh, German Society of
      Rheumatology) guidelines emphasized the significance of coordinated
      multidisciplinary care and rehabilitation of patients with inflammatory rheumatic
      diseases. Nationwide data from the German pension insurance funds showed that
      inpatient rehabilitation due to rheumatoid arthritis (RA) varied by a factor of
      2.6 between the different German states. From 2000 to 2012 rehabilitation
      measures were reduced by one third, most significantly in men with ankylosing
      spondylitis (AS). Rehabilitation measures because of RA or AS were provided up to
      14 times more frequently by the German statutory pension insurance scheme
      compared with a large compulsory health insurance which is responsible for
      rehabilitation measures after retirement. In rehabilitation centers with high
      numbers of patients with inflammatory rheumatic diseases, higher structural and
      process quality were demonstrated. In 2011 a total of 40 % of RA patients in the
      national database of the collaborative arthritis centers showed medium or severe
      functional limitations. Among these disabled RA patients inpatient rehabilitation
      was reduced by about 50 % between 1995 and 2011. Out of all RA patients from
      outpatient rheumatology care with severe functional limitations 38 % had no
      functional restoration therapy within the previous 12 months with a high
      variation between rheumatologists. Experiences from other European countries may
      inspire German rheumatologists and other involved health professionals to
      initiate a wider range of rehabilitative interventions in the future. 

PMID- 24659151
TI  - [Nailfold capillaroscopy].
AB  - Capillaroscopy is performed to evaluate the morphology, frequency and blood flow
      of nailfold capillaries as well as relevant extracapillary changes in rheumatic
      conditions. The main indication is the differentiation between primary and
      secondary Raynaud's phenomenon. Various rheumatic conditions show different and
      partially typical pathognomonic alterations of the microcirculation or capillary
      patterns. This simple, noninvasive, inexpensive and effective technique is well
      suited for early diagnosis, especially of connective tissue diseases. The
      specific significance is highest for systemic sclerosis which is the most
      frequently evaluated entity. The corresponding microscopic alterations allow
      stage-adapted conclusions concerning the acuity of inflammation to be formed.
      That is not the only reason why capillaroscopy represents an important tool in
      follow-up controls and together with other techniques, such as flow measurement
      by laser Doppler, further conclusions can be drawn. 

PMID- 24659152
TI  - [Interference immune system and bone repair].

PMID- 24659154
TI  - [Hospital financing in 2014. Relevant changes for rheumatology].
AB  - As with others medical disciplines hospitals specialized in rheumatology again
      face heavy economic burdens in 2014. To meet the challenges knowledge of the new
      German diagnosis-related groups (G-DRG) system, the legislative framework and
      current jurisprudence can be helpful. The following article presents the major
      changes and discusses the consequences for hospitals specialized in rheumatology.

PMID- 24659153
TI  - [Recommendations for use of rituximab in patients with rheumatoid arthritis].
AB  - Treatment with rituximab (RTX) has been approved since 2006 for patients with
      rheumatoid arthritis who previously failed to respond to tumor necrosis factor
      (TNF) inhibitor therapy or who experienced side effects. In these updated
      treatment recommendations new data relating to evaluation of the therapeutic
      response, retreatment, the role of predictive factors as well as safety data are
      incorporated and discussed. 

PMID- 24659155
TI  - Effects of a 12-week endurance training program on the physiological response to
      psychosocial stress in men: a randomized controlled trial.
AB  - The present study experimentally tested the cross-stressor adaptation hypothesis
      by examining whether endurance exercise training leads to reductions in the
      physiological stress response to a psychosocial stressor. We randomly assigned
      149 healthy men to a 12-week exercise training, relaxation training, or a wait
      list control group. Before and after intervention we assessed the groups'
      physical fitness (lactate testing) and compared their physiological stress
      responses to the Trier Social Stress Test for Groups in terms of salivary free
      cortisol, heart rate (HR) and heart rate variability (HRV); the final sample
      consisted of 96 subjects. As hypothesized, the exercise training significantly
      improved fitness and reduced stress reactivity in all three parameters; however,
      it only improved stress recovery in terms of HR. The relaxation program reduced
      only cortisol, but not HR or HRV reactivity; no changes emerged for the control
      group. The findings suggest that the cross-stressor adaptation hypothesis is
      valid for cardiovascular as well as endocrine stress reactivity.

PMID- 24659157
TI  - T cell immune responses in psoriasis.
AB  - A central role for T cells and their cytokines in the pathogenesis of psoriasis
      has been proposed; however, there are controversies over the details of this
      issue. The goal of this study is to summarise currently available data on the
      importance of T cells in psoriasis pathogenesis. A systematic review of the
      English medical literature was conducted by searching PubMed, Embase, ISI Web of
      Knowledge, and Iranian databases including Iranmedex, and SID for studies on
      associations between the involvement of T cell subsets and psoriasis. The results
      of the present study indicate that alterations in the number and function of
      different subsets of T-cells are associated with psoriasis. It appears that
      studies on T cell subsets contributed to understanding the immunopathogenesis of
      psoriasis. In addition, it may have provided novel therapeutic opportunities in
      ameliorating immunopathologies.

PMID- 24659156
TI  - Perceived discrimination as a stressor for close relationships: identifying
      psychological and physiological pathways.
AB  - Approaching the inverse association between perceived discrimination and close
      relationship functioning from a stress and coping framework, we propose and test
      a novel model incorporating psychological (emotion dysregulation) and
      physiological (chronic inflammation) pathways. Analyses of data from a sample of
      African American participants (N = 592) enrolled in the Midlife in the United
      States (MIDUS) study revealed support for the proposed model. Specifically,
      results from structural equation modeling analyses showed that perceived
      discrimination was indirectly associated with increased emotion dysregulation
      (venting and denial) through stressor appraisals and directly associated with
      increased inflammation (interluekin-6, e-selectin and c-reactive protein).
      Furthermore, relationship strain with family, friends and spouses was associated
      with greater levels of emotion dysregulation and chronic inflammation. Overall,
      the proposed model fit the data well and provides support for new avenues of
      research on the social, psychological and physiological correlates of perceived
      discrimination and close relationship functioning. To conclude, evidence for the
      proposed biopsychosocial model is summarized and directions for future research
      on these topics are discussed.

PMID- 24659158
TI  - Effects of enzymatic hydrolysis on the allergenicity of whey protein
      concentrates.
AB  - Cow's milk whey consists of many protein components and some of them are antigens
      to human and known to modulate immune responses. Enzymatic hydrolysis is a useful
      method to modify proteins with allergenicity. The objective of this study was to
      identify whether the in vitro enzymatic hydrolysis could reduce the allergenicity
      of whey protein concentrates (WPC). In this study, WPC were hydrolyzed by trypsin
      and twenty-four BALB/c mice were divided into three groups and fed with WPC
      formula and WPC hydrolysates formula, while the control mice received milk-free
      diet. The results revealed that there was no significant difference between the
      body weights among all groups. WPC-fed mice produced an elevated spleen
      lymphocyte proliferation level than WPC hydrolysates-fed mice and also produced
      higher levels of WPC-specific IgE in intestinal tract and serum in comparison to
      WPC hydrolysates-fed mice and control group. Significant up-regulation of plasma
      histamine levels were also observed and showed the same trend with IgE. The
      secretions of IL-4 and IL-5 were significantly enhanced by WPC. WPC significantly
      suppressed the secretion of IFN-gamma while hydrolysates of WPC significantly
      increased the secretion of IFN-gamma compared to control group. These results
      suggest that hydrolysis may play a role to reduce the allergenicity of WPC.

PMID- 24659159
TI  - Component-resolved diagnosis (CRD): Is it worth it? frequency and differentiation
      in rhinitis patients with mite reactivity.
AB  - Component-resolved diagnosis (CRD) using microarray technology has recently been
      introduced with the aim to improve diagnosis of allergy. The aim of this study
      was to compare performance of this allergen microarray to those of an established
      extract-based skin prick testing (SPT).45 patients with allergic rhinitis were
      studied (16 children and 29 adults). SPT to Dermatophagoides pteronyssinus,
      Dermatophagoides farinae and Blomia tropicalis extracts and allergen microarray
      ImmunoCAP ISAC were carried out for all patients. Forty out of 45 patients
      demonstrated positive SPT to all mite extracts tested. These 40 patients were
      considered to be mite-allergic based on the positive SPT results. The remaining 5
      patients with negative SPT to any mite extracts were classified as non-mite
      allergic. Comparatively, based on the microarray results, only 34 mite-allergic
      patients had detectable serum IgE to at least one of the mite allergen components
      tested whereas 6 patients with positive SPT to mite extracts showed no detectable
      IgE reactivity to any of the components tested. One non-mite allergic patient had
      a positive test- Blo t 5. Der p 10-positive patients also reacted to other cross
      reactive tropomyosin from anisakis (Ani s 3) (25%), cockroach (Bla g 7) (50%) and
      shrimp (Pen m 1) (75%). CRD is a reliable tool for the diagnosis of allergy to
      mites. Der p 10 might be a useful indicator to identify a subset of mite-allergic
      patient that have additional sensitization due to cross-reactivity and thus
      allows selection of patients for immunotherapy.

PMID- 24659160
TI  - The effects of high fat, low carbohydrate and low fat, high carbohydrate diets on
      tumor necrosis factor superfamily proteins and proinflammatory cytokines in
      C57BL/6 mice.
AB  - There has been considerable inconsistency regarding the potential relationship
      between dyslipidemia and bone metabolism. The inflammatory stimulation through
      the receptor activator of the nuclear factor kappa-B ligand (RANKL)/ receptor
      activator of the nuclear factor kappa-B (RANK)/ osteoprotegerin (OPG) pathway
      could be the infrastructural mechanism for hypercholesterolemia-induced bone
      loss.In this study, we investigated the effect of dyslipidemia on RANKL and OPG
      alongside with pro-inflammatory cytokines. Thirty male C57Bl/6 mice (4 weeks old)
      were randomized to two purified diet groups (15 animals in each group), high fat,
      low carbohydrate diet (HFLCD) and its matched low fat, high carbohydrate diet
      (LFHCD). After 12 weeks of feeding in standard situations, the plasma
      concentration of lipid profile, interleukin (IL) 1Beta, IL-6, tumor necrosis
      factor-alpha (TNF-alpha) and RANKL, OPG, and RANKL: OPG ratio were measured.In
      the present study, although the body weight significantly increased during 12
      weeks in HFLCD and LFHCD groups, there were no significant differences in food
      intake, food efficiency ratio and weight gain between the two groups. The LFHCD
      group had significantly higher median RANKL and RANKL/OPG ratio. There was no
      significant difference in plasma IL-1beta, IL-6 and TNF-alpha concentration
      between LFHCD and HFLCD groups.These unexpected findings from LFHCD, that seem to
      be as a result of its higher carbohydrate proportion in comparison to HFLCD,
      implicate dietary carbohydrate rather than dietary fat as a more significant
      nutritional factor contributing to change in RANKL level and RANKL: OPG ratio.

PMID- 24659161
TI  - Alleviation of experimental allergic encephalomyelitis in C57BL/6 mice by soy
      daidzein.
AB  - Experimental allergic encephalomyelitis (EAE) is considered as the murine model
      of multiple sclerosis. Daidzein a phytostrogenic compound of soy is known to
      impose immunomodulatory and antioxidative effects. We conducted this study to
      assess the potential protective and therapeutic effects of daidzein on allergic
      encephalomyelitis.C57BL/6 mice were induced with allergic encephalomyelitis using
      myelin oligodendrocyte glycoprotein (35-55) and received daidzein or dimethyl
      sulfoxide as the vehicle control. To assess the protective effect of daidzein,
      the mice were administered with 20 mg/kg of daidzein from 21 days prior to 21
      days post EAE induction on a daily basis. To evaluate the therapeutic effect of
      daidzein, mice were fed with 300 mg/kg daidzein after the appearance of the first
      clinical signs for 10 days. One day after the last gavage, the mice were
      sacrificed. Spleen and brain were removed for further histological and
      immunological analysis.Feeding mice with low dose of daidzein prior to disease
      induction did not affect disease severity. However, treating with high dose of
      daidzein after the onset of the disease reduced interferon-gamma and interleukin
      12 secretion, enhanced interleukin-10 production, suppressed lymphocyte
      proliferation, and decreased cytotoxicity as judged by lactate dehydrogenase
      release.In conclusion, daidzein reduced the extent of demyelination and disease
      severity. Chronic oral therapy with low dose of daidzein did not prevent
      experimental autoimmune encephalomyelitis. However, high doses of daidzein could
      prohibit disease exacerbation.  

PMID- 24659162
TI  - Expression of CD11b as an adhesion molecule on neutrophils in children with
      Kawasaki disease.
AB  - Inflammation of blood vessels is a characteristic feature of Kawasaki disease.
      Neutrophils play a key role in the inflammatory responses where movement of
      neutrophils toward the site of inflammation depends on CD11b/CD18 expression as
      adhesion molecules on these cells. The purpose of this study was to investigate
      CD11b/CD18 expression in patients with Kawasaki disease upon diagnosis and after
      treatment.The study included 20 children with Kawasaki disease aged from 3 months
      to 8 years. Mean fluorescence intensity of CD11b levels on diagnosis and at 1-2
      and 6 weeks after intravenous immunoglobulin (IVIG) therapy was measured in these
      patients. Level of CD11b was measured in age-matched healthy children and febrile
      children (each 21) as negative and positive controls, respectively.Mean
      fluorescence intensity of CD11b in Kawasaki patients was lower than that of the
      control groups before and after 1-2 weeks of IVIG therapy. There were no
      significant differences in CD11b in Kawasaki patients either with aneurysm or
      without aneurysm. The CD11b levels at the diagnosis time and after treatment with
      IVIG in our patients with Kawasaki were lower than the control groups.

PMID- 24659163
TI  - YKL-40 in Asthma and its correlation with different clinical parameters.
AB  - It has been suggested that elevated serum level of YKL-40 could be a marker for
      asthma and its severity. Along with few published studies, we investigated its
      correlation with asthma and its severity as well as spirometric indices.114
      patients with asthma and 114 healthy controls underwent the assessment of serum
      level of YKL-40 (by ELISA) and spirometric indices. Pearson's coefficient
      determined the correlation between the variables and multivariate linear
      regression analysis was used for adjusting the effect of different probable
      confounding factors.Serum levels of YKL-40 were significantly higher in the
      asthmatic patients compared to those in healthy people (p<0.001). We also found a
      significant correlation between YKL-40 serum level and spirometric indices even
      after adjusting the effects of other variables.We report for the first time in an
      Iranian population that YKL-40 may be a good diagnostic marker of asthma in
      serum. 

PMID- 24659164
TI  - The persian version of the chronic urticaria quality of life questionnaire:
      factor analysis, validation, and initial clinical findings.
AB  - Chronic urticaria (CU) also known as chronic idiopathic urticaria results in a
      lowered quality of life (QoL). Disease specific questionnaires are necessary to
      assess QoL in CU patients. Chronic Urticaria Quality of Life Questionnaire (CU
      Q2oL) is the only available and validated disease specific questionnaire in the
      assessment of QoL in CU patients originally developed in Italian language. The
      aim of the current study was to develop the Persian version of the CU-Q2oL with
      an acceptable reliability and validity.Using the standard methods provided by
      guidelines, CU-Q2oL was translated into Persian. A total number of 110 patients
      with confirmed diagnosis of CU were asked to fill the questionnaire.
      Determination of scales was performed in addition to checking the data for
      internal consistency and known group validity. Urticaria activity score 7 (UAS7)
      was used to assess the severity of the CU in the population study. The 6
      dimensional scale of Persian CU-Q2oL was determined using the Exploratory Factor
      Analysis. About 68% of the variance was explained by these 6 factor structure
      higher than 59.9% of the original Italian version.All 6 factors showed acceptable
      internal consistency as measured by Cronbach alpha coefficient. There was a
      significant correlation between UAS7 and total CU-Q2oL score. UAS7 and the
      presence of angioedema were predictors of CU-Q2oL score.The Persian version of CU
      Q2oL was shown to be a valid and reliable tool to be used in the future clinical
      studies. Cultural considerations must be kept in mind in adoption of CU-Q2oL to
      other languages.  

PMID- 24659165
TI  - Papillon Lefevre Syndrome and footsteps of mycobacterium tuberculosis.
AB  - Papillon Lefevre Syndrome ( PLS ) is a very rare genetic syndrome that only less
      than 500 cases have reported in the world. Patients have a typical cutaneous
      involvement with hyperkeratosis especially on the soles and palms and early
      shedding of primary teeth. Internal organs involvement such as liver abscess has
      been presented as case reports. This is for the first time that a genetically
      documented PLS with footsteps of mycobacterium tuberculosis in liver and kidney
      will report. 

PMID- 24659166
TI  - Oleaceae pollen allergy and its cross-reactivity in the mediterranean area in the
      context of globalization.
AB  - Opening frontiers has led in the last two decades to a massive migration of
      Romanians to Spain and Italy, two countries known to have large areas planted
      with olives. Romania owns large areas planted with ash forests. Because of cross
      reactivity between these two trees belonging to the Oleaceae family and the big
      allergenic potential of olive pollens, after a number of years of residence in
      these countries, many Romanians will present allergic respiratory symptoms of
      rhinitis and asthma, both in the season of olive pollination and ash pollination.

PMID- 24659167
TI  - Esomeprazole: a safe alternative to lansoprazole allergy?
AB  - Proton pump inhibitors (PPIs) are widely prescribed drugs in daily practice.
      Allergic reactions, even small number of anaphylactic reactions to PPIs have been
      reported. Omeprazole, lansoprazole, pantoprazole, rapeprazol and esomeprazole are
      classified in the same group. Despite the similarity of biochemical structures
      among these drugs, presence of cross-reactivity between PPIs is controversial.1,2
      In this letter, we present 3 lansoprazole allergy cases, who were prescribed and
      took esomeprazole safely after allergic reactions to lansoprazole. 

PMID- 24659168
TI  - IL-13 gene polymorphisms and their association with atopic asthma and rhinitis in
      Pakistani patients.

PMID- 24659169
TI  - Standardizing Leucocyte PNH clone detection: An international study.
AB  - Background: Consensus and Practical Guidelines for robust high-sensitivity
      detection of glycophosphatidylinostitol (GPI)-deficient structures on Red Blood
      Cells (RBCs) and White Blood Cells (WBCs) in Paroxysmal Nocturnal Hemoglobinuria
      (PNH) were recently published. Methods: UK NEQAS LI issued 3 stabilized samples
      manufactured to contain no PNH cells (normal), approximately 0.1% and 8% PNH
      leucocyte populations, together with instrument-specific SOPs and pre-titered
      antibody cocktails to 19 international laboratories experienced in PNH testing.
      Samples were tested using both standardized protocol/reagents and in-house
      protocols. Additionally, samples were issued to all participants in the full PNH
      EQA programmes. Results: Expert laboratory results showed no difference in PNH
      clone detection rates when using standardized and their 'in-house' methods though
      lower variation around the median was found for the standardized approach
      compared to in-house methods. Neutrophil analysis of the sample containing an 8%
      PNH population, for example, showed an interquartile range of 0.48% with the
      standardized approach compared with 1.29% for in-house methods. Results from the
      full EQA group showed the greatest variation with an inter-quartile range of 1.70
      and this was demonstrated to be significantly different (P<0.001) to the
      standardized cohort. Conclusions: The results not only demonstrate that
      stabilized whole PNH blood samples are suitable for use with currently
      recommended high-sensitivity reagent cocktails/protocols but also highlight the
      importance of using carefully selected conjugates alongside the standardized
      protocols. While much more variation was seen amongst the full UK NEQAS LI EQA
      group, the standardized approach lead to reduced variation around the median even
      for the experienced laboratories. (c) 2014 Clinical Cytometry Society.

PMID- 24659170
TI  - Task predictability influences the variable foreperiod effect:  evidence of task
      specific temporal preparation.
AB  - Temporal preparation usually results in enhanced performance in choice reaction
      time tasks. The present study investigated to what extent temporal preparation
      involves increased readiness for task-specific processing requirements as opposed
      to increased task-independent readiness. Participants performed either a pitch, a
      letter, or a color discrimination task within a variable foreperiod paradigm and
      tasks alternated regularly between auditory and visual discriminations. In
      separate blocks of trials, the upcoming visual discrimination task was either
      predictable or unpredictable. We observed the standard variable foreperiod effect
      for both visual discrimination tasks irrespective of task predictability.
      Importantly, however, the variable foreperiod effect was larger when the visual
      discrimination task was predictable than when it was unpredictable. These results
      suggest that temporal preparation in choice reaction time tasks involves
      increased readiness for both task-independent and task-specific processing
      requirements.

PMID- 24659171
TI  - Extreme weather event in spring 2013 delayed breeding time of Great Tit and Blue
      Tit.
AB  - The impact of climatic changes on life cycles by re-scheduling the timing of
      reproduction is an important topic in studies of biodiversity. Global warming
      causes and will probably cause in the future not only raising temperatures but
      also an increasing frequency of extreme weather events. In 2013, the winter in
      central and north Europe ended late, with low temperatures and long-retained snow
      cover--this extreme weather phenomenon acted in opposition to the increasing
      temperature trend. In 2013, thermal conditions measured by the warmth sum in the
      period 15 March-15 April, a critical time for early breeding passerines, went far
      beyond the range of the warmth sums for at least 40 preceding years. Regardless
      of what was the reason for the extreme early spring 2013 and assuming that there
      is a potential for more atypical years because of climate change, we should look
      closely at every extreme phenomenon and its consequences for the phenology of
      organisms. In this paper, we report that the prolonged occurrence of winter
      conditions during the time that is crucial for Blue Tit (Cyanistes caeruleus) and
      Great Tit (Parus major) reproduction caused a substantial delay in the onset of
      egg laying in comparison with typical springs.

PMID- 24659172
TI  - Sirolimus-eluting versus paclitaxel-eluting stent in primary angioplasty: a
      pooled patient-level meta-analysis of randomized trials.
AB  - Large interests have been focused on the role of drug-eluting stents in the
      setting of ST-segment elevation myocardial infarction (STEMI) and concerns have
      emerged regarding an higher risk of stent thrombosis. Aim of the current study
      was to perform a meta-analysis using individual patient data to evaluate the long
      term safety and effectiveness of sirolimus-eluting stent (SES) as compared to
      paclitaxel-eluting stent (PES) in patients undergoing primary percutaneous
      coronary intervention (PCI) for STEMI. The literature was scanned by formal
      searches of electronic databases (MEDLINE and CENTRAL). We examined all completed
      randomized trials of SES versus PES for STEMI. No language restriction was
      applied. Primary study endpoint was the occurrence of major adverse cardiac
      events (MACE). Secondary endpoints were the occurrence of death, reinfarction,
      stent thrombosis, target-vessel revascularization (TVR). Individual patient data
      were obtained from 4 out of 5 trials identified, including a total of 1,000
      patients, 504 (50.4 %) randomized to SES and 496 (49.6 %) randomized to PES. At
      long-term follow-up (1,021 [372-1,351] days), no difference was observed between
      SES and PES in terms of TVR (10 vs 11.6 %, HR [95 % CI 0.73 [0.45-1.16], p =
      0.18, p het = 0.92]) (primary endpoint) or death (9.4 vs 10.4 %, HR [95 % CI 0.95
      [0.58-1.54], p = 0.82, p het = 0.89]), reinfarction (8.2 vs 10.4 %, HR [95 % CI
      0.91 [0.53-1.57], p = 0.73, p het = 0.83]), stent thrombosis (7.4 vs 4.6 %, HR
      [95 % CI 1.04 [0.55-2.05], p = 0.92, p het = 0.65]), and MACE (10 vs 13.6 %,
      HR[95 % CI 0.86 [0.63-1.18], p = 0.36, p het = 0.84]) (secondary endpoints). The
      present pooled patient-level meta-analysis demonstrates that, among STEMI
      patients undergoing primary PCI, SES and PES are associated with a similar
      outcome at long-term follow-up, in terms of death, reinfarction, stent
      thrombosis, TVR and MACE.

PMID- 24659173
TI  - Impact of homocysteine-thiolactone on plasma fibrin networks.
AB  - Epidemiologic studies have shown that hyperhomocysteinemia is an independent risk
      factor for vascular disease. Homocysteine (Hcy) circulates as different species,
      mostly protein bound, and approximately 1% as its reduced form and the cyclic
      thioester homocysteine-thiolactone (HTL). Despite the level of plasma thiolactone
      being markedly low, detrimental effects are related to its high reactivity. HTL
      reacts with proteins by acylation of free basic amino groups; in particular, the
      epsilon-amino group of lysine residues forms adducts and induces structural and
      functional changes in plasma proteins. In order to assess the effects of HTL on
      plasma fibrin networks, a pool of normal plasma incubated with HTL (100, 500 and
      1,000 MUmol/L, respectively) was evaluated by global coagulation tests and fibrin
      formation kinetic assays, and the resulting fibrin was observed by scanning
      electron microscopy. HTL significantly prolonged global coagulation tests in a
      concentration-dependent manner with respect to control, and increases were up to
      14.5%. Fibrin formation kinetic parameters displayed statistically significant
      differences between HTL-treated plasma and control in a concentration-dependent
      way, showing higher lag phase and lower maximum reaction velocity and final
      network optical density. Electron microscopy analysis of HTL plasma networks
      revealed a compact architecture, with more branches and shorter fibers than
      control. We can conclude that HTL induced a slower coagulation process, rendering
      more tightly packed fibrin clots. Since these features of the networks have been
      related to impaired fibrinolysis, the N-homocysteinylation reactions would be
      involved in the prothrombotic effects associated to hyperhomocysteinemia.

PMID- 24659174
TI  - Olanzapine-induced hypoglycemia in anorexia nervosa.

PMID- 24659176
TI  - Genome tailoring powered production of isobutanol in continuous CO2/H2 blend
      fermentation using engineered acetogen biocatalyst.
AB  - The cell energy fraction that powered maintenance and expression of genes
      encoding pro-phage elements, pta-ack cluster, early sporulation, sugar ABC
      transporter periplasmic proteins, 6-phosphofructokinase, pyruvate kinase, and
      fructose-1,6-disphosphatase in acetogen Clostridium sp. MT871 was re-directed to
      power synthetic operon encoding isobutanol biosynthesis at the expense of these
      genes achieved via their elimination. Genome tailoring decreased cell duplication
      time by 7.0 +/- 0.1 min (p < 0.05) compared to the parental strain, with intact
      genome and cell duplication time of 68 +/- 1 min (p < 0.05). Clostridium sp.
      MT871 with tailored genome was UVC-mutated to withstand 6.1 % isobutanol in
      fermentation broth to prevent product inhibition in an engineered commercial
      biocatalyst producing 5 % (674.5 mM) isobutanol during two-step continuous
      fermentation of CO2/H2 gas blend. Biocatalyst Clostridium sp. MT871RG- 11IBR6 was
      engineered to express six copies of synthetic operon comprising optimized
      synthetic format dehydrogenase, pyruvate formate lyase, acetolactate synthase,
      acetohydroxyacid reductoisomerase, 2,3-dihydroxy-isovalerate dehydratase,
      branched-chain alpha-ketoacid decarboxylase gene, aldehyde dehydrogenase, and
      alcohol dehydrogenase, regaining cell duplication time of 68 +/- 1 min (p < 0.05)
      for the parental strain. This is the first report on isobutanol production by an
      engineered acetogen biocatalyst suitable for commercial manufacturing of this
      chemical/fuel using continuous fermentation of CO2/H2 blend thus contributing to
      the reversal of global warming.

PMID- 24659177
TI  - Identification and characterization of a novel alkaline alpha-amylase Amy703
      belonging to a new clade from Bacillus pseudofirmus.
AB  - Alkaline alpha-amylases are of great interest in desizing processes and detergent
      industries. Here, an alkaline alpha-amylase gene amy703 from an alkaliphilic
      Bacillus pseudofirmus strain was cloned and sequenced. Its encoding product,
      Amy703, might represent a new clade of alpha-amylase family, because it shared
      only 35 % highest identity with all amylases characterized up to date and was not
      clustered into any subfamilies with amylase activity in glycoside hydrolase
      family 13. Heterologous expression and characterization of Amy703 showed that it
      is a metalloenzyme with maximal activity at 40  degrees C and pH 9.0. Its
      activity was significantly enhanced by 2- and 2.48-fold at the presence of 10 mM
      Ca2+ and Mg2+, respectively, while Hg2+ was a strong inhibitor of Amy703. Amy703
      has a higher affinity (Km = 3.92 mg/ml) for soluble starch compared to many other
      alkaline amylases. The computer modeling of its structure indicated that Amy703
      contains typical amylase domains and a loop region appearing to bind the
      substrates. Site-directed mutagenesis suggested that a conserved residue Glu550
      was essential for the activity of Amy703, and proposed it working together with
      other two residues to constitute a catalytic triad (Asp521, Glu550, and Asp615).

PMID- 24659179
TI  - A novel regio-specific cyclosporin hydroxylase gene revealed through the genome
      mining of Pseudonocardia autotrophica.
AB  - The regio-specific hydroxylation at the 4th N-methyl leucine of the
      immunosuppressive agent cyclosporin A (CsA) was previously proposed to be
      mediated by a unique cytochrome P450 hydroxylase (CYP), CYP-sb21 from the rare
      actinomycetes Sebekia benihana. Interestingly, a different rare actinomycetes
      species, Pseudonocardia autotrophica, was found to possess a different regio
      selectivity, the preferential hydroxylation at the 9th N-methyl leucine of CsA.
      Through an in silico analysis of the whole genome of P. autotrophica, we describe
      here the classification of 31 total CYPs in P. autotrophica. Three putative CsA
      CYP genes, showing the highest sequence homologies with CYPsb21, were
      successfully inactivated using PCR-targeted gene disruption. Only one knock-out
      mutant, DeltaCYP-pa1, failed to convert CsA to its hydroxylated forms. The
      hydroxylation activity of CsA by CYP-pa1 was confirmed by CYP-pa1 gene
      complementation as well as heterologous expression in the CsA non-hydroxylating
      Streptomyces coelicolor. Moreover, the cyclosporine regio-selectivity of CYP-pa1
      expressed in the DeltaCYP-sb21 S. benihana mutant strain was also confirmed
      unchanged through cross complementation. These results show that preferential
      regio-specific hydroxylation at the 9th N-methyl leucine of CsA is carried out by
      a specific P450 hydroxylase gene in P. autotrophica, CYP-pa1, setting the stage
      for the biotechnological application of CsA regioselective hydroxylation.

PMID- 24659178
TI  - High-throughput sequencing of amplicons for monitoring yeast biodiversity in must
      and during alcoholic fermentation.
AB  - We compared pyrosequencing technology with the PCR-ITS-RFLP analysis of yeast
      isolates and denaturing gradient gel electrophoresis (DGGE). These methods gave
      divergent findings for the yeast population. DGGE was unsuitable for the
      quantification of biodiversity and its use for species detection was limited by
      the initial abundance of each species. The isolates identified by PCR-ITSRFLP
      were not fully representative of the true population. For population dynamics,
      high-throughput sequencing technology yielded results differing in some respects
      from those obtained with other approaches. This study demonstrates that 454
      pyrosequencing of amplicons is more relevant than other methods for studying the
      yeast community on grapes and during alcoholic fermentation. Indeed, this high
      throughput sequencing method detected larger numbers of species on grapes and
      identified species present during alcoholic fermentation that were undetectable
      with the other techniques.

PMID- 24659180
TI  - Preparation of catalytic materials using ionic liquids as the media and
      functional components.
AB  - Ionic liquids (ILs) have attracted much attention due to their unique properties
      and wide application potential in a variety of fields. The unusual properties of
      ILs provide numerous opportunities to design and prepare arious advanced
      materials, including highly efficient catalysts. In recent years, synthesis of
      different kinds of catalytic materials and their applications in chemical
      reactions have been studied extensively and have become a very interesting area.
      Herein, we present a review on the synthesis of catalytic materials using ILs as
      the media and/or functional components; the important and widely investigated
      topics are discussed, including mainly metal nanocatalysts/IL, functional
      IL/support, metals or metal oxides/IL/support, polymeric ILs (PILs) catalysts,
      and the performances of catalytic systems are highlighted. An outlook for this
      interesting area is also given at the end of the article. 

PMID- 24659182
TI  - Exposure to air pollution and respiratory symptoms during the first 7 years of
      life in an Italian birth cohort.
AB  - BACKGROUND: Ambient air pollution has been consistently associated with
      exacerbation of respiratory diseases in schoolchildren, but the role of early
      exposure to traffic-related air pollution in the first occurrence of respiratory
      symptoms and asthma is not yet clear. METHODS: We assessed the association
      between indexes of exposure to traffic-related air pollution during different
      periods of life and respiratory outcomes in a birth cohort of 672 newborns (Rome,
      Italy). Direct interviews of the mother were conducted at birth and at 6, 15
      months, 4 and 7 years. Exposure to traffic-related air pollution was assessed for
      each residential address during the follow-up period using a Land-Use Regression
      model (LUR) for nitrogen dioxide (NO2) and a Geographic Information System (GIS)
      variable of proximity to high-traffic roads (HTR) (>10 000vehicles/day). We used
      age-specific NO2 levels to develop indices of exposure at birth, current, and
      lifetime time-weighted average. The association of NO2 and traffic proximity with
      respiratory disorders were evaluated using logistic regression in a longitudinal
      approach (Generalised Estimating Equation). The exposure indexes were used as
      continuous and categorical variables (cut-off points based on the 75th percentile
      for NO2 and the 25th percentile for distance from HTRs). RESULTS: The average NO2
      exposure level at birth was 37.2 MUg/m(3) (SD 7.2, 10-90th range 29.2-46.1).
      There were no statistical significant associations between the exposure indices
      and the respiratory outcomes in the longitudinal model. The odds ratios for a 10
      ug/m(3) increase in time-weighted average NO2 exposure were: asthma incidence
      OR=1.09; 95 CI% 0.78 to 1.52, wheezing OR=1.07; 95 CI% 0.90 to 1.28, shortness of
      breath with wheezing OR=1.16; 95 CI% 0.94 to 1.43, cough or phlegm apart from
      cold OR=1.11; 95 CI% 0.92 to 1.33, and otitis OR=1.08; 95 CI% 0.89 to 1.32.
      Stronger but not significant associations were found considering the 75th
      percentile of the NO2 distribution as a cut-off, especially for incidence of
      asthma and prevalence of wheeze (OR=1.41; 95 CI% 0.88 to 2.28 and OR=1.27; 95 CI%
      0.95 to 1.70, respectively); the highest OR was found for wheezing (OR=2.29; 95
      CI% 1.15 to 4.56) at the 7-year follow-up. No association was found with distance
      from HTRs. CONCLUSIONS: Exposure to traffic-related air pollution is only weakly
      associated with respiratory symptoms in young children in the first 7 years of
      life.

PMID- 24659183
TI  - Mental health correlates of past homelessness in Latinos and Asians.
AB  - Mental illness and addiction are strongly associated with homelessness, yet few
      studies have shown how these relationships vary across ethnic categories that are
      underrepresented in the homeless population. This study draws from the National
      Latino and Asian American Survey to examine mental health and substance abuse
      correlates of homelessness amongst Latinos and Asians living in the United
      States. Clinical and institutional factors associated with homelessness varied by
      ethnicity. Among Latinos, alcohol abuse or dependence, conduct disorder and
      intermittent explosive disorder were risk factors for homelessness, while
      attending a religious service more than once a week was a protective factor.
      Among Asians, mood disorder was a risk factor as were health problems and
      receiving welfare in the past. Understanding ethnicity-specific correlates of
      homelessness may guide culturally nuanced mental health prevention and
      intervention efforts.

PMID- 24659184
TI  - Oncostatin M receptor is a novel therapeutic target in cervical squamous cell
      carcinoma.
AB  - Cervical carcinoma is the second most common cause of cancer deaths in women
      worldwide. Treatments have not changed for decades and survival rates for
      advanced disease remain low. An exciting new molecular target for the treatment
      of cervical squamous cell carcinoma (SCC), and possibly for SCCs at other
      anatomical sites, is the oncostatin M receptor (OSMR). This cell surface cytokine
      receptor is commonly copy number gained and overexpressed in advanced cervical
      SCC, changes that are associated with significantly worse clinical outcomes. OSMR
      overexpression in cervical SCC cells results in enhanced responsiveness to the
      major ligand oncostatin M (OSM), which induces several pro-malignant effects,
      including a pro-angiogenic phenotype and increased cell migration and
      invasiveness. OSMR is a strong candidate for antibody-mediated inhibition, a
      strategy that has had a major impact on haematological malignancies and various
      solid tumours such as HER2-positive breast cancers.

PMID- 24659185
TI  - Protrusion-guided extracellular vesicles mediate CD30 trans-signalling in the
      microenvironment of Hodgkin's lymphoma.
AB  - Classical Hodgkin's lymphoma (cHL)-affected lymphoid tissue contains only a few
      malignant Hodgkin and Reed-Sternberg (HRS) cells, which are disseminated within a
      massive infiltrate of reactive cells. In particular, the innate immune infiltrate
      is deemed to support tumour growth by direct cell-cell interaction. Since they
      are rarely found in close proximity to the malignant cells in situ, we
      investigated whether cHL-derived extracellular vesicles might substitute for a
      direct cell-cell contact. We studied the crosstalk of the transmembrane proteins
      CD30 and CD30 ligand (CD30L) because they are selectively expressed on HRS and
      innate immune cells, respectively. Here, we showed that HRS cells released both
      the ectodomain as a soluble molecule (sCD30) and the entire receptor on the
      surface of extracellular vesicles. The vesicle diameter was 40-800 nm, as
      determined by cryo- and immune electron microscopy. In addition to CD30, typical
      extracellular vesicle markers were detected by mass spectrometry and flow
      cytometry, including tetraspanins, flotillins, heat shock proteins and adhesion
      molecules. In contrast to sCD30, vesicles caused a CD30-dependent release of
      interleukin-8 in CD30L(+) eosinophil-like EoL-1 cells and primary granulocytes
      from healthy donors, underscoring the functionality of CD30 on vesicles. In
      extracellular matrix (ECM)-embedded culture of HRS cells, a network of actin and
      tubulin-based protrusions guided CD30(+) vesicles into the micro-environment.
      This network targeted CD30(+) vesicles towards distant immune cells and caused a
      robust polarization of CD30L. Confocal laser scanning microscopy of 30 um
      sections showed a CD30 vesicle-containing network also in cHL-affected lymphoid
      tissue of both mixed-cellularity and nodular sclerosing subtypes. This network
      might facilitate the communication between distant cell types in cHL tissue and
      allow a functional CD30-CD30L interaction in trans. The tubulin backbone of the
      network may provide a target for the therapy of cHL with antitubulin-based CD30
      antibody constructs.

PMID- 24659187
TI  - Clinical outcomes with on-label and off-label use of the transcatheter heart
      valve in the United States.
AB  - OBJECTIVE: We explored the efficacy, safety, and clinical consequences of on
      label and off-label transcatheter aortic valve replacement (TAVR) in the real
      world setting. BACKGROUND: The transcatheter heart valve (THV) was initially
      approved only for transfemoral (TF) delivery (on-label use) during TAVR in
      inoperable patients with severe aortic stenosis (AS). Because of lack of
      alternative options in TAVR-eligible patients with inadequate TF access, other
      routes have been utilized for THV implantation (off-label use), outcomes of which
      were previously unknown. METHODS: Consecutive patients with severe inoperable AS
      who underwent clinical TAVR at our site were enrolled in a prospective database.
      Fifty subjects underwent TF-TAVR (on-label group), while non-TF routes were
      utilized in 60 subjects (off-label group). Procedural events, 30-day clinical
      outcomes, and 1-year all-cause mortality data were analyzed. RESULTS: Technical
      device success was similar between on-label and off-label groups (88% vs. 87%,
      respectively; P = 0.92), as was the incidence of procedural complications and 30
      day clinical events. The on-label group had lower 1-year all-cause death rate
      (12%) compared to the off-label group (32%; P = 0.02). The 1-year all-cause
      mortality in the off-label group was comparable to published clinical trial and
      registry data on TAVR, and appeared lower than historical outcomes with
      conservative medical therapy. CONCLUSION: On-label use of the THV in the real
      world setting was associated with favorable survival outcomes compared to off
      label TAVR and historical data. Off-label use of the THV appeared to be safe and
      effective when used in select patients with inoperable AS who are not eligible
      for TAVR via TF approach.

PMID- 24659186
TI  - [Consequences of hospitalisations on smoking behaviour in psychiatric and somatic
      inpatients].
AB  - BACKGROUND: To examine the differences and potential changes that occur in
      smoking habits among psychiatric and somatic patients due to and during their
      hospital stay in a general hospital. METHODS: Inpatients of three departments
      (psychiatry,cardiology, pulmology) were given a questionnaire that asked for
      epidemiologic data and their smoking habits,including the Fagerstrom-Test. In
      order to achieve sufficient data, the questionnaire was administered twice on two
      different dates. Primary goal of this examination was to determine a potential
      change in smoking behaviour whereas the secondary goal was to check for
      differences between psychiatric and somatic inpatients and within the psychiatric
      diagnostic groups according to their smoking habits respectively. According to a
      lack of normal distribution of the data non parametric tests undvisual
      classifying were used for statistical analysis. RESULTS: A substantial proportion
      (26.4 %) of psychiatric inpatients reported an increase in cigarette consumption
      or have restarted or newly started smoking cigarettes are due to their admission.
      On the other hand, none of the somatic patients did so, actually they showed
      higher proportion of being non-smokers. There were statistically significant
      differences between psychiatric and somatic patients in two age-groups due to
      their change in smoking habits and severity of nicotine dependence as measured by
      the Fagerstrom-test. Among the psychiatric patients sampled, those with
      schizophrenia and affective disorders showed high prevalence of being highly
      addicted smokers in 85.7 and 44.4 % respectively. CONCLUSIONS: As a result of
      this small sample and hindered comparability of somatic and psychiatric groups of
      inpatients further investigations are needed to evaluate the influence of
      hospitalisations on smoking behaviour and to tailor suitable actions

PMID- 24659188
TI  - Construction of an immunochromatographic determination system for N1,N12
      diacetylspermine.
AB  - BACKGROUND: N(1),N(12)-diacetylspermine (DiAcSpm) is a recently identified tumor
      marker. Its concentration increases in the urine of cancer patients at early
      clinical stages. To utilize this characteristic feature and thus contribute to
      the early detection of cancer, we developed an immunochromatographic
      determination system for DiAcSpm. METHODS: We examined the factors that affect
      the performance and stability of our determination system, including antibody
      selection and the conditions for the formation of stably dispersed antibody
      coated gold nanoparticles. We then tested the performance of the system by
      determining the DiAcSpm concentration in human urine samples. RESULTS: We
      constructed an immunochromatographic strip using anti-DiAcSpm antibody-coated
      gold nanoparticles in the conjugate pad and an acetylspermine-protein conjugate
      (a DiAcSpm mimic) immobilized on the analyzing membrane. The use of the
      immunochromatographic strip and an immunochromato-reader allowed for the
      quantitative determination of DiAcSpm in the range of 20 to 700 nM. The
      analytical values obtained by this method were well correlated with those
      determined by a colloidal gold aggregation procedure using an automatic
      biochemical analyzer. The immunochromatographic strip was stable for at least 8
      weeks at 50 degrees C. CONCLUSIONS: A competitive immunochromatographic device
      for DiAcSpm determination was developed in this study. This simple device will
      contribute to increasing the opportunities for early cancer detection and timely
      care.

PMID- 24659189
TI  - The past, present, and future of bioresorbable vascular scaffolds.

PMID- 24659190
TI  - Some evidence for unconscious lie detection.
AB  - To maximize survival and reproductive success, primates evolved the tendency to
      tell lies and the ability to accurately detect them. Despite the obvious
      advantage of detecting lies accurately, conscious judgments of veracity are only
      slightly more accurate than chance. However, findings in forensic psychology,
      neuroscience, and primatology suggest that lies can be accurately detected when
      less-conscious mental processes (as opposed to more-conscious mental processes)
      are used. We predicted that observing someone tell a lie would automatically
      activate cognitive concepts associated with deception, and observing someone tell
      the truth would activate concepts associated with truth. In two experiments, we
      demonstrated that indirect measures of deception detection are significantly more
      accurate than direct measures. These findings provide a new lens through which to
      reconsider old questions and approach new investigations of human lie detection. 

PMID- 24659191
TI  - Facial movements strategically camouflage involuntary social signals of face
      morphology.
AB  - Animals use social camouflage as a tool of deceit to increase the likelihood of
      survival and reproduction. We tested whether humans can also strategically deploy
      transient facial movements to camouflage the default social traits conveyed by
      the phenotypic morphology of their faces. We used the responses of 12 observers
      to create models of the dynamic facial signals of dominance, trustworthiness, and
      attractiveness. We applied these dynamic models to facial morphologies differing
      on perceived dominance, trustworthiness, and attractiveness to create a set of
      dynamic faces; new observers rated each dynamic face according to the three
      social traits. We found that specific facial movements camouflage the social
      appearance of a face by modulating the features of phenotypic morphology. A
      comparison of these facial expressions with those similarly derived for facial
      emotions showed that social-trait expressions, rather than being simple one-to
      one overgeneralizations of emotional expressions, are a distinct set of signals
      composed of movements from different emotions. Our generative face models
      represent novel psychophysical laws for social sciences; these laws predict the
      perception of social traits on the basis of dynamic face identities. 

PMID- 24659192
TI  - Psychological strategies for winning a geopolitical forecasting tournament.
AB  - Five university-based research groups competed to recruit forecasters, elicit
      their predictions, and aggregate those predictions to assign the most accurate
      probabilities to events in a 2-year geopolitical forecasting tournament. Our
      group tested and found support for three psychological drivers of accuracy:
      training, teaming, and tracking. Probability training corrected cognitive biases,
      encouraged forecasters to use reference classes, and provided forecasters with
      heuristics, such as averaging when multiple estimates were available. Teaming
      allowed forecasters to share information and discuss the rationales behind their
      beliefs. Tracking placed the highest performers (top 2% from Year 1) in elite
      teams that worked together. Results showed that probability training, team
      collaboration, and tracking improved both calibration and resolution. Forecasting
      is often viewed as a statistical problem, but forecasts can be improved with
      behavioral interventions. Training, teaming, and tracking are psychological
      interventions that dramatically increased the accuracy of forecasts. Statistical
      algorithms (reported elsewhere) improved the accuracy of the aggregation. Putting
      both statistics and psychology to work produced the best forecasts 2 years in a
      row. 

PMID- 24659193
TI  - Scapulothoracic arthroscopy for symptomatic snapping scapula: a prospective
      cohort study with two-year mean follow-up.
AB  - BACKGROUND: Snapping scapula is characterized by crepitus between the scapula and
      the chest wall due to abnormal tissue at this site. Surgical treatment, when
      needed, may be either open or arthroscopic. The aim of this study was to evaluate
      prospectively the clinical outcomes of arthroscopic decompression in ten subjects
      with symptomatic snapping scapula. PATIENTS AND METHODS: Ten subjects, five men
      and five women, mean age 24 years, were treated by arthroscopy after unsuccessful
      conservative management for 6 months. Clinical outcomes were evaluated with the
      Western Ontario Rotator Cuff (WORC) index, Constant-Murley score (CS), and simple
      shoulder test (SST). Follow-up was at 3 and 6 months; the final evaluation was
      conducted at a mean interval of 24 months. The final and preoperative X-rays were
      compared. RESULTS: The WORC index increased significantly at 3 (p < 0.05), 6 (p <
      0.01), and 24 months (p < 0.01). Similar outcomes were found for the CS at all 3
      follow-up points (3 months, p < 0.05; 6 months, p < 0.01; 24 months, p < 0.01).
      Mean "yes" responses on the SST were 9.8 +/- 1.4 at 3 months (p < 0.05), 10.2 +/-
      1.2 at 6 months (p < 0.01), and 10.6 +/- 1.2 at 24 months (p < 0.01). X-ray
      examination depicted flattening of the anterior surface of the superior-medial
      angle of the scapula in the five patients who had had bone resection, whereas no
      significant difference with preoperative imaging was detected in the five
      patients who were managed by bursectomy and debridement alone. CONCLUSIONS:
      Arthroscopy is a feasible and minimally invasive treatment for painful snapping
      scapula syndrome. Comparative clinical trials are needed to collect conclusive
      data to state that it is the most suitable treatment for this condition.

PMID- 24659194
TI  - Destructive septic arthritis of shoulder in adults.
AB  - BACKGROUND: Late sequelae of septic arthritis of the glenohumeral joint are very
      rare and represent a potentially devastating condition that can result in
      irreversible changes at the level of joint and surrounding soft tissues.
      MATERIALS AND METHODS: Between January 2001 and December 2010, ten patients were
      treated at our institution for late sequelae of septic arthritis of the shoulder.
      There were eight men and two women with a mean age of 67.9 years (range 62-74
      years). Eight of ten patients had previously received three or more intra
      articular or subacromial injections. Surgical treatment consisted of open joint
      debridement, humeral head resection and implantation of an antibiotic spacer
      followed by a 6-8-week course of intravenous antibiotics. RESULTS: White blood
      cell count, C-reactive protein and erythrocyte sedimentation rate normalized
      between 6 and 8 weeks postoperatively in all patients. No recurrent infection was
      observed in any patient. Postoperatively, the mean Constant score was 37 (range
      28-46) and mean DASH score was 54 (range 40-69), demonstrating a very limited
      function in these patients. There was a trend toward improved outcome scores in
      patients who underwent early surgical debridement. Five patients underwent
      delayed reconstruction with a reverse shoulder prosthesis, and at minimum 1-year
      follow-up, the mean Constant score was 56 (range 47-69) and mean DASH score was
      33 (31-38). CONCLUSIONS: Antibiotic spacers are able to deliver antibiotics
      locally to the infected tissue while reducing the dead space and stabilizing the
      glenohumeral joint. An early, aggressive management of the infection is essential
      to maximize clinical outcomes and avoid either significant destruction or
      ankylosis of the shoulder joint.

PMID- 24659195
TI  - Anatomic reinsertion of the distal biceps tendon rupture through a single
      anterior approach: extensile or mini-invasive approach? A retrospective study at
      mean 45-month follow-up.
AB  - PURPOSE: To evaluate and compare clinical results and complication rate of a
      standard and mini-invasive reconstruction technique for distal biceps tendon
      rupture. METHODS: Twenty-eight cases of biceps tendon rupture were evaluated at
      mean 45-month follow-up. A standard anterior approach was used in 19 cases, and a
      less invasive anterior approach was used in nine cases. Suture anchors were used
      for tendon reconstruction in all cases. Elbow range of motion (ROM), subjective
      strength recovery, time to return to work and sports activities, and
      complications were recorded. Disability of the Arm, Shoulder and Hand Score
      (DASH) the Oxford Elbow Score (OES), and the Mayo Elbow Performance Score (MEPS)
      were obtained for all patients. RESULTS: Mean ROM recovery was almost complete.
      Mean subjective strength recovery allowed full return to sports and work in 93 %
      of cases, within mean 3-month postoperative. Mean DASH, OES, and MEPS scores were
      good. The clinically relevant complications rate was 17.8 %, all associated with
      the standard extensile approach group (Group A). Asymptomatic heterotopic
      ossifications were detected in four cases (14.3 %), not affecting functional
      recovery. CONCLUSIONS: Clinical results and complications rate of anatomical
      reconstruction of the distal biceps tendon rupture were comparable to the
      literature. Comparison between Group A and B showed no significant differences in
      terms of ROM, and OES and MEPS scores. Strength recovery, time to return to
      sports and work, and DASH score showed a positive trend in Group B. The
      clinically relevant complications rate was 0 % in Group B and 26 % in Group A.

PMID- 24659196
TI  - Shoulder hemiarthroplasty for complex humeral fractures: a 5 to 10-year follow-up
      retrospective study.
AB  - BACKGROUND: Shoulder hemiarthroplasty is considered a standard treatment in case
      of complex proximal humeral fractures. However, great variability affects the
      clinical outcomes. In this work, we examined the clinical and radiographic
      outcomes in a series of patients treated with hemiarthroplasty for 3- and 4-part
      humeral fractures and focused on factors affecting the final result. MATERIALS
      AND METHODS: In this study, we included 27 patients who had received a shoulder
      hemiarthroplasty between 2001 and 2005 at our institution. These patients were
      evaluated at an average of 7.2 years after surgery. All patients were managed
      within 10 days from trauma by the same surgeon and underwent the same time
      scheduled rehabilitation program. Average age at surgery was 71.9 years. RESULTS:
      Implant survival was 88.9 %. At the latest follow-up, mean DASH and SST-12 scores
      were 26.8 and 6.5, respectively. Mean Constant-Murley score was 52.4.
      Tuberosities complications and reduction in the acromion-humeral distance were
      negatively related to clinical outcome. Age at surgery displayed a negative
      correlation with clinical outcome, despite not reaching the statistical
      significance. This is mainly due to great variability in the elder group of
      patients. CONCLUSIONS: Shoulder hemiarthroplasty is a useful and effective
      solution for complex humeral fractures, with good results in the majority of
      patients. However, outcomes display a great variability in relation to X-ray
      alterations and age at surgery. A careful attention in patient selection is
      needed in order to standardize the clinical results associated with this kind of
      prosthetic implant.

PMID- 24659197
TI  - Irreparable rotator cuff tears: a novel classification system.
AB  - BACKGROUND: Irreparable rotator cuff tears can be managed by several approaches.
      However, current tear classifications fail to reflect the wide variety of their
      presentation, which has important clinical and prognostic implications. METHODS:
      We describe a novel classification system based on preoperative imaging findings
      and intraoperative observation where each cuff tendon (numbered sequentially: 1
      supraspinatus, 2-infraspinatus, 3-teres minor, and 4-subscapularis) is assessed
      intraoperatively for reducibility to the footprint; tendons with reparable
      lesions are assessed for fatty degeneration (which predicts healing potential)
      and given a plus if degeneration is <50 % (Fuchs stage I-II/Goutallier stage 0
      II) or a minus if it is >=50 % (Fuchs stage III/Goutallier stage III-IV).
      RESULTS: The proposed system (1) allows more consistent and reproducible
      classification of cuff tears where at least one tendon is irreparable; (2)
      results in more accurate diagnosis; (3) guides in treatment selection; and (4)
      ensures better outcomes and realistic patient expectations. CONCLUSIONS: The
      novel classification system can contribute to develop increasingly exhaustive and
      reproducible classification models.

PMID- 24659198
TI  - Reverse shoulder arthroplasty without subscapularis repair for the treatment of
      proximal humeral fractures in the elderly.
AB  - PURPOSE: The aim of this study was to evaluate the short-term results after
      reverse shoulder arthroplasty (RSA) for proximal humeral fractures in elderly
      patients. METHODS: The same surgical technique was adopted in all patients: the
      procedure was performed through a deltopectoral approach, the subscapularis was
      always resected, and a positioning jig was used to implant the cemented humeral
      component in the desired height and in 20 degrees  of retroversion. Nineteen
      consecutive patients, affected by complex fractures of the proximal humerus, were
      operated in a 3-year period by the same surgeon at a single institution. All the
      patients were female, with a mean age of 75 years (range 70-83). RESULTS: Fifteen
      patients were evaluated at an average follow-up of 22 months (range 12-46
      months). A postoperative infected hematoma was the only recorded complication.
      The absolute Constant score averaged 45.7 (range 19-69), while the relative and
      normalized scores averaged 65.1 (range 33-97) and 58.5 (range 24-91),
      respectively. The average Shoulder Pain and Disability Index (SPADI) score was 39
      (range 6-89). X-rays showed healing of the greater tuberosity to the humeral
      diaphysis in nine shoulders. CONCLUSIONS: RSA is an established treatment option
      for elderly patients with proximal humeral fractures, particularly when general
      and local conditions are predictive of failure with hemiarthroplasty. Even though
      clinical results were quite variable in this series of patients, the adoption of
      a standardized surgical technique allowed to minimize postoperative
      complications. Subscapularis repair does not seem a critical factor for
      preventing implant dislocation, but its influence on functional results needs
      further investigation.

PMID- 24659199
TI  - Hemiarthroplasty versus reverse shoulder arthroplasty: comparative study of
      functional and radiological outcomes in the treatment of acute proximal humerus
      fracture.
AB  - PURPOSE: To compare functional and radiographic results of reverse prosthesis
      versus hemiarthroplasty after complex displaced proximal humeral fractures in
      elderly patients when adequate ORIF cannot be achieved and prosthetic shoulder
      replacement is required. METHODS: From 2008 to 2012, 67 patients were treated
      with hemiarthroplasty or reverse arthroplasty. We evaluated 53 cases with an
      average follow-up of 27.5 months (range 12-64). Twenty-eight patients with an
      average age of 71.4 years were treated with a hemiarthroplasty and 25 patients
      with an average age of 77.3 years with a reverse prosthesis. All patients were
      assessed before and after surgery by Constant-ASES-DASH score, strength in
      abduction, ER1, ER2, and X-rays. RESULTS: In hemiarthroplasty group, we observed
      a mean Constant score of 42.3 pt, ASES score 51.3 pt, and DASH score 46.1, with
      an average strength of 1.3 lb in abduction and of 3.7 lb in ER1 and 1.8 lb in
      ER2. In reverse arthroplasty group, we measured a mean Constant of 56.2 pt, ASES
      69.3 pt, and DASH score 40.4, with an average strength of 4.3 lb in abduction and
      of 3.3 lb in ER1 and 3.2 lb in ER2. Radiographically, it is interesting to
      observe that greater tuberosity healing rate was 37 % in hemiarthroplasty group
      compared to 84 % in reverse arthroplasty group. About complications, the highest
      rate was recorded in the hemiarthroplasty group. CONCLUSION: Reverse shoulder
      arthroplasty indication is steadily increasing in acute displaced proximal
      humeral fracture. Pain and articular movement results appear better than those
      with hemiarthroplasty. Our data are similar to the international literature.

PMID- 24659200
TI  - Strength recovery after proximal humeral fractures treated with locking plate.
AB  - PURPOSE: The aim of this study is to understand whether the isokinetic strength
      could be a valid objective data of functional recovery evaluating a group of
      patients with proximal humeral fractures treated with open reduction and internal
      fixation with locking plate comparing the clinical and functional recovery
      (isokinetic strength) with the not involved side. METHODS: Seventy patients
      underwent surgery with locking plate placement for proximal humeral fractures.
      The strength of each patient's shoulders, both involved and not involved, was
      evaluated using isokinetic tests and Constant-Murley score. Finally, the study
      included 48 patients and the mean follow-up of 33 months. RESULTS: The functional
      outcome showed no significant differences between operated and not operated
      shoulder. CONCLUSIONS: This study shows that the assessment of the force can be
      supported by use of tools such as the evaluation with isokinetic machines with
      the advantage of having, in this way, an objective data on the functional
      recovery. LEVEL OF EVIDENCE: III.

PMID- 24659201
TI  - Optimal glenoid component inclination in reverse shoulder arthroplasty. How to
      improve implant stability.
AB  - PURPOSE: The purpose of this study is to demonstrate that inferior inclination of
      the glenosphere is a protecting factor from joint dislocation in reverse total
      shoulder replacement. The hypothesis is that an average of 10 degrees  of
      inferior inclination of the glenoid component would determine a significant
      inferior rate of dislocation as compared to neutral inclination. METHODS: A
      retrospective case (dislocation)-control (stability of the implant) study was
      performed. Inclusion criteria were the homogeneity of the prosthetic model and
      availability of pre- and postoperative imaging of the shoulder, including antero
      posterior and axillary X-ray views. Glenoid and glenosphere inclination were
      calculated according to standardized methods. Difference in between the angles
      determined the inferior tilt. RESULTS: Thirty-three cases fit the inclusion
      criteria. Glenoid and glenosphere inclination measured, respectively, 74.1
      degrees  and 83.5 degrees . The average tilt of the glenosphere measured 9.4
      degrees . The average tilt in stable patients was 10.2 degrees . Tilt in patients
      with atraumatic dislocation measured, respectively, -6.9 degrees  (superior tilt)
      and 2.4 degrees , while it was 8.3 degrees  for the patient with traumatic
      instability. The association between the tilt of glenosphere and atraumatic
      dislocation was significant. CONCLUSIONS: A 10 degrees  inferior tilt of the
      glenoid component in reverse shoulder arthroplasty is associated with a reduced
      risk of dislocation when compared to neutral tilt.

PMID- 24659202
TI  - Elbow ulnar collateral ligament reconstruction: clinical, radiographic, and
      ultrasound outcomes at a mean 3-year follow-up.
AB  - BACKGROUND: Ulnar collateral ligament (UCL) has the main function to be stress
      resistant to elbow valgus overload. Multilayer tears require a reconstruction
      with a tendon graft. In this study, we report the clinical, radiographic, and
      ultrasound outcomes after tendon graft reconstruction for symptomatic UCL
      insufficiency. MATERIALS AND METHODS: Among twenty-six subjects underwent elbow
      UCL reconstruction from 2006 to 2012, fifteen were available to be evaluated at a
      mean follow-up of 36 months. Preoperative assessment included clinical
      examination and MRI. The outcome measures were the Mayo Elbow Performance Score
      (MEPS); the Oxford Elbow Score (OES); the Disabilities of the Arm, Shoulder, and
      Hand (DASH); and the Conway-Jobe Scale. Overall population was postoperatively
      investigated with X-ray and ultrasound (US). Reconstruction was performed with
      autograft (palmaris longus) in five cases and allograft (semitendinosus) in ten
      cases using the figure-of-eight configuration (five cases), the docking technique
      (eight cases), or a fixation with screws (two cases). RESULTS: We found a
      significant improvement in postoperative MEPS, OES, and DASH scores (p < 0.01).
      One case was unsatisfied and required an additional procedure of ulnar nerve
      transposition 12 months after the reconstruction. X-ray showed calcifications
      along the graft in ten cases. At US examination, all the grafts assessed appeared
      anatomically intact without structural changes, and the dynamic examination
      showed a slight medial laxity with the valgus stress maneuver without pain or
      other sign of medial instability. CONCLUSIONS: This study confirms the efficacy
      of the graft reconstruction for chronic UCL insufficiency and introduces fresh
      insight on the role of musculoskeletal ultrasound to evaluate the reconstructed
      UCL.

PMID- 24659203
TI  - Factors affecting choice of open surgical techniques in elbow stiffness.
AB  - BACKGROUND: We analyzed the clinical outcomes of stiff elbow open treatment to
      assess factors affecting the choice of surgical procedures in a consecutive
      series of patients followed up prospectively. MATERIALS AND METHODS: Forty-one
      patients, mean aged 48 years, were evaluated. Elbow stiffness was caused by post
      traumatic osteoarthritis in 32 patients, primary osteoarthritis in seven and
      rheumatoid arthritis in two. Stiffness was classified as mixed and extrinsic in
      28 and 13 cases, respectively. Seventeen ulno-humeral arthroplasties (UHA), seven
      UHA with radiocapitellar replacement, six UHA with radial head replacement, ten
      total elbow replacement and one UHA with anconeus interposition were performed.
      Mayo Elbow Performance Score (MEPS), modified-American Shoulder and Elbow
      Surgeons (m-ASES) and Q-DASH scores were used for the pre- and post-operative
      evaluation. RESULTS: Mean follow-up was 25 months. The average increase in MEPS
      and m-ASES was 45 and 41, respectively. The average decrease in Q-DASH and the
      average increase in m-ASES pain were 43 and 21, respectively. The mean increase
      in flection, extension, pronation and supination was 29 degrees , 25 degrees , 18
      degrees  and 17 degrees , respectively. All the differences were statistically
      significant. CONCLUSIONS: Strictly customized open surgery of elbow stiffness, by
      taking into account the clinical value of each patient's pathoanatomical
      conditions, yields satisfactory functional results in majority of cases. In
      particular, the degree and site of elbow cartilage wear proved to be the factors
      affecting the choice of treatment most. Treatment should be aimed at removing the
      causes of pain and at recovering range of motion.

PMID- 24659204
TI  - Does immobilization position after arthroscopic rotator cuff repair impact work
      quality or comfort?
AB  - PURPOSE: The purpose of this study was to quantify subjective discomfort and
      decrease in working performance in patients submitted to arthroscopic rotator
      cuff repair. METHODS: We enrolled 101 asymptomatic administrative employees (mean
      age 55). Subjects were asked to write a text using Microsoft Word and to make a
      table using Microsoft Excel, with and without shoulder braces which kept the
      right shoulder in neutral (brace A) and internal rotation (brace B). Total time
      needed to complete the tests and number of mistakes committed were annotated.
      Furthermore, a questionnaire to assess the subjective and interpersonal
      discomfort caused by the braces was compiled. Data were submitted to statistical
      analysis. RESULTS: When any brace is worn, both times and mistakes are higher
      than those registered without brace (p < 0.02). Both times and mistakes are
      higher for brace B in comparison with brace A (p < 0.02). Subjects wearing brace
      B had a severe/very severe discomfort degree three times higher than that
      registered in subjects wearing brace A. Finally, 91 % of subjects preferred brace
      A to brace B. DISCUSSION: If the choice of the brace is not supported by
      biological or clinical advantages, we recommend to use the brace that keeps the
      arm at the side, since it ensures better working performance and lower
      discomfort. It also received the greatest satisfaction of the respondents. LEVEL
      OF EVIDENCE: IV.

PMID- 24659205
TI  - An overview about elbow instability.

PMID- 24659206
TI  - Differential microRNA profile and post-transcriptional regulation exist in
      systemic lupus erythematosus patients with distinct autoantibody specificities.
AB  - PURPOSE: Systemic lupus erythematosus (SLE) patients have anti-nuclear
      autoantibodies directed against dsDNA and RNA-associated antigens (extractable
      nuclear antigens; ENA). In this study, we investigated the differences in
      microRNA (miRNA) expression and its biological implications in SLE patients with
      distinct autoantibody specificities. METHODS: The SLE patients were grouped into
      three subsets based on the type of autoantibodies present in their sera (anti-
      ENA+ group with autoantibodies against ENA alone; antidsDNA+ group having
      autoantibodies against dsDNA only, and anti-ENA+dsDNA+ group having
      autoantibodies to both dsDNA and ENA). Global miRNA expression profiling was done
      for each of these three groups using TaqMan(r) low density miRNA arrays. RESULTS:
      We report that different sets of miRNAs are dysregulated in SLE patients with
      different autoantibody specificities. Further, Ingenuity pathway analysis (IPA)
      software revealed specific biological pathways that were targeted by miRNAs
      dysregulated in different SLE subsets. Molecules involved in cell cycle and
      cytoskeleton remodeling were the prime targets of miRNAs dysregulated in anti
      ENA+ patients whereas miRNAs dysregulated in anti-dsDNA+ patients were found to
      be implicated in multiple cytokine signaling pathways. IPA analysis of gene
      targets of miRNAs commonly dysregulated in all three SLE subsets identified
      several metabolic-, hormone-, and interferon-related pathways to be affected.
      CONCLUSION: The differential miRNA expression in patients with distinct
      autoantibodies is suggestive of different regulatory mechanisms operating among
      them. Based on these observations, we are hopeful that this 'sub-grouping'
      approach could be used to identify other defective processes associated with
      varying disease manifestations in SLE and may be considered when designing
      therapeutic interventions.

PMID- 24659207
TI  - The borderline between legality and illegality of providing health services in
      anaesthesiology and intensive care units.

PMID- 24659208
TI  - Can soy intake affect serum uric acid level? Pooled analysis  from two 6-month
      randomized controlled trials among Chinese  postmenopausal women with prediabetes
      or prehypertension.
AB  - PURPOSE: Hyperuricemia is a recognized risk factor for cardiovascular diseases.
      Soy foods contain a moderate amount of purine and may predispose to raised serum
      uric acid (UA). However, no study has examined the long-term effect of soy intake
      on UA levels. We examined whether consumption of soy foods and isoflavone
      extracts for 6 months altered serum UA. METHODS: The analysis included two
      randomized controlled trials (soy protein trial and whole soy trial) among total
      450 postmenopausal women with either prehypertension or prediabetes. We conducted
      a pooled analysis by combining participants from both the soy flour and soy
      protein groups (combined soy foods group), participants from both the isoflavone
      and daidzein groups (combined isoflavone group) and participants from both milk
      placebo groups. Fasting venous samples were obtained at baseline and the end of
      the trial for serum UA analysis. RESULTS: In the pooled data, 417 subjects
      completed the study according to protocol. The baseline serum UA levels were
      comparable among the three combined groups. There was a lower decrease in UA
      levels among women in the combined soy foods group compared with women in the
      other two groups (p = 0.028 and 0.026). The net decrease and % decrease in UA
      were 14.5 MUmol/L (95 % CI 1.93-25.6, p = 0.023) or 4.9 % (95 % CI 1.3-8.5 %, p =
      0.023) between the combined soy foods group and placebo group. CONCLUSIONS: Among
      Chinese postmenopausal women with either prehypertension or prediabetes, soy
      intake did not increase urate levels.

PMID- 24659209
TI  - Estimating endurance shuttle walk test speed using the six-minute walk test in
      people with chronic obstructive pulmonary disease.
AB  - The objective of this study was to derive and validate an equation to estimate
      the speed for the endurance shuttle walk test (ESWT) using results from the six
      minute walk test (6MWT) in patients with chronic obstructive pulmonary disease
      (COPD). Participants with diagnosed COPD (n = 84) performed two incremental
      shuttle walk tests (ISWTs) and two 6MWTs. ESWT speed was calculated from the ISWT
      results using the original published method. An equation was derived, which
      directly related six-minute walk distance (6MWD) to ESWT speed. The derived
      equation was validated in a different group of people with COPD (n = 52). There
      was a strong correlation between average 6MWD and the calculated ESWT speed (r =
      0.88, p < 0.001). The ESWT speed (kilometre per hour) was estimated using the
      following equation: 0.4889 + (0.0083 * 6MWD). The mean difference (+/-limits of
      agreement) between ESWT speeds was calculated using the original published method
      and found to be 0.03 (+/-0.77) km/hour. When the ISWT is not the test of choice
      for clinicians, the 6MWT can be used to accurately estimate the speed for the
      ESWT. 

PMID- 24659210
TI  - Attendance at pulmonary rehabilitation classes: an exploration of demographic,
      physiological and psychological factors that predict completion of treatment.
AB  - Pulmonary rehabilitation (PR) is an effective treatment for people with chronic
      obstructive pulmonary disease (COPD). However, uptake and adherence to
      rehabilitation is poor and non-adherence is associated with poorer clinical
      outcomes. This study investigated the factors that might predict an individual
      completing his/her PR programme. Demographic, physiological and psychological
      data were collected from routine assessment information. Non-completers (N = 213)
      who dropped out after initial assessment were compared with completers (N = 438)
      who attended all 6 weeks of PR programme. Regression analysis indicated that
      smoking status was the strongest predictor for completing PR programme, that is,
      ex-smokers were 2.6 times (95% confidence interval (CI) = 1.7-3.9) and those who
      had never smoked were 2.5 times (95% confidence interval (CI) = 1.1-5.7) more
      likely to complete in comparison with those who were current smokers. Scoring
      better on psychological well-being measures (odds ratio = 1.6; 95% CI = 1.2-1.9)
      was also a strong predictor. The findings suggest the areas that could be
      addressed to enhance adherence to rehabilitation, for example, targeted
      interventions for clients who continue to smoke and for those who require support
      for psychological distress. 

PMID- 24659211
TI  - Does gender affect asthma control in adult asthmatics?
AB  - Several studies have shown gender differences in prevalence of asthma but there
      is little information about asthma control. In this study, we aimed to evaluate
      the effect of gender on asthma control in adult asthmatics. Medical records of
      242 patients older than 18 years of age who regularly visited the allergy unit
      were evaluated. Standardized asthma questionnaires like the asthma control test
      (ACT) were performed. ACT scores, clinical characteristics, and demographic data
      such as smoking status, education, duration and severity of asthma, atopic
      status, family history of asthma, analgesic hypersensitivity, number of emergency
      visits, and hospitalization in the previous year were compared based on gender.
      In this study, 77.3% of the patients were female. Mean age, body mass index, and
      duration of asthma were 39.0 +/- 0.7, 27.3 +/- 0.3, and 6.6 +/- 0.4 years,
      respectively. Of the total, 14.9% of the patients were smokers. Also, 55.8% of
      them were graduated from middle school, 22.7% from high school, and 14% from
      university. Atopy rate was 57%. Analgesic hypersensitivity was found in 18.6% of
      them. There was 30.2% family history of asthma. The asthma severity was mild in
      45.5%, moderate in 40.9%, and severe in 13.6% of the patients. One-third of the
      patients were admitted to emergency room; 1/10th were hospitalized due to asthma
      in the previous year. ACT scores indicated complete control in 67.8%, partial
      control in 17.8%, and uncontrolled asthma in 14.5%. Comparing the results of
      males with females having asthma, there was no statistically significant
      difference between the two gender according to ACT scores and clinical
      characteristics. Finally, the results conclude that there was no effect of gender
      on asthma control assessed with standardized questionnaire in adult asthmatics. 

PMID- 24659212
TI  - YouTube as a source of chronic obstructive pulmonary disease patient education: a
      social media content analysis.
AB  - The aim of the present study is to conduct a social media content analysis of
      chronic obstructive pulmonary disease (COPD) patient education videos on YouTube.
      A systematic search protocol was used to locate 223 videos. Two independent
      coders evaluated each video to determine topics covered, media source(s) of
      posted videos, information quality as measured by HONcode guidelines for posting
      trustworthy health information on the Internet, and viewer exposure/engagement
      metrics. Over half the videos (n = 113, 50.7%) included information on medication
      management, with far fewer videos on smoking cessation (n = 40, 17.9%). Most
      videos were posted by a health agency or organization (n = 128, 57.4%), and the
      majority of videos were rated as high quality (n = 154, 69.1%). HONcode adherence
      differed by media source (Fisher's exact test = 20.52, p = 0.01), however with
      user-generated content receiving the lowest quality scores. Overall level of user
      engagement as measured by number of "likes," "favorites," "dislikes," and user
      comments was low (median range = 0-3, interquartile range = 0-16) across all
      sources of media. Study findings suggest that COPD education via YouTube has the
      potential to reach and inform patients; however, existing video content and
      quality varies significantly. Future interventions should help direct individuals
      with COPD to engage with high-quality patient education videos on YouTube that
      are posted by reputable health organizations and qualified medical professionals.
      Patients should be educated to avoid and/or critically view low-quality videos
      posted by individual YouTube users who are not health professionals. 

PMID- 24659213
TI  - A Stroop effect emerges in the processing of complex Chinese   characters that
      contain a color-related radical.
AB  - Three experiments examined whether a Stroop effect emerges in the processing of
      complex Chinese characters that contain a color-related radical. In Experiment 1,
      a Stroop effect occurred when participants responded to the black or white color
      of the simple characters [Chinese character: see text] (black) and [Chinese
      character: see text] (white) by making a left or right keypress. For Experiment
      2, in which the stimuli were complex characters whose meanings were unrelated to
      color but that contained [Chinese character: see text] or [Chinese character: see
      text] as a radical, a Stroop effect also occurred, although it was smaller than
      in Experiment 1. Furthermore, this Stroop effect as a function of radical meaning
      was shown again in Experiment 3 for low-frequency complex characters but not high
      frequency ones. These results suggest that the semantic representations of the
      complex characters' color-related radicals are accessed in the context of a
      Stroop color word task, especially for low-frequency characters. Reduction of the
      Stroop effect in complex characters composed of one radical with color meaning
      and one without is similar to dilution of the Stroop effect that occurs when a
      color word is accompanied by a neutral word. Possible implications of the results
      for accounts of Stroop dilution are discussed.

PMID- 24659214
TI  - Magnetic resonance imaging of the iliac crest: age estimation   in under-20
      soccer players.
AB  - Age assessment of living individuals represents a valuable tool in both forensic
      medicine and sports medicine. In soccer, age-related tournaments play an
      important role in guaranteeing equal chances to the competitors. However, age
      estimations in this field should not rely on imaging methods that include
      exposure to radiation. Therefore, the present study investigates the
      possibilities of magnetic resonance imaging (MRI) of the iliac crest apophysis
      for the purpose of evaluating skeletal maturation in under-20 (U-20) soccer
      players. To this end, gradient echo 3D sequences of the whole pelvis of 152 male
      tournament soccer players between 18 and 22 years of age were prospectively
      evaluated. A four stage classification system was applied for the assessment of
      the apophyseal ossification. Reliable stage determination was possible in all
      cases. Further sub-classification did not appear feasible due to the limitations
      of MRI. Analysis of the statistical parameters showed that age medians increased
      steadily from stage to stage. However, they did not allow for further
      differentiation of skeletal maturity in the cohort studied. Thus, MRI of the
      iliac crest appears to be generally suitable in age diagnostics of living
      individuals, but further investigations, especially in a cohort of individuals
      aged between 10 and 20 years, are needed in order to establish this method as
      novel criterion in sports or forensic medicine.

PMID- 24659215
TI  - Synthesis of a water-soluble conjugated polymer based on thiophene for an aqueous
      processed hybrid photovoltaic and photodetector device.

PMID- 24659216
TI  - Totally implantable vascular access devices 30 years after the first  procedure.
      What has changed and what is still unsolved?
AB  - The first placement of a totally implantable central venous access device (TIVAD)
      was performed in 1982 at the MD Anderson Cancer Center in Houston by John
      Niederhuber, using the cephalic vein-exposed by surgical cut-down-as route of
      access to central veins. After that, TIVADs proved to be safe and effective for
      repeated administration of drugs, blood, nutrients,and blood drawing for testing
      in many clinical settings, especially in the oncologic applications. They allow
      for administration of hyperosmolar solutions, extreme pH drugs, and vescicant
      chemotherapeutic agents,thus improving venous access reliability and overall
      patients' quality of life. Despite the availability of a variety of devices, each
      showing different features and performances, many issues are still unsolved. The
      aim of this review article is to point out what has changed since the first
      implant of a TIVAD, and what it is still matter of debate, thus needing more
      investigation. Topics analyzed here include materials, choice of the veins and
      techniques of implantation, role of ultrasound (US) guidance in central venous
      access, position of catheter tip assessment, TIVAD-related infection and
      thrombosis, and quality of life issues.

PMID- 24659217
TI  - Motor disability, clinical complications, quality of life, and survival in
      patients with cancer: a plausible scenario.

PMID- 24659218
TI  - Post-release monitoring: the Brazilian system, its aims and requirements for
      information.
AB  - The Brazilian National Biosafety Committee approved in 2011 a new post release
      monitoring system for environmental releases of genetically modified organisms.
      It has a number of novel features in comparison with other established or
      proposed systems. The new system also allows the proponent to ask for monitoring
      exemption. General surveillance forms the basis of the monitoring system, similar
      to the European model, but differs markedly in the way it operates. While the
      European proposal is based on monitoring measurable variables extracted from
      environmental observations, from baselines previously established for multiple
      protection targets, the Brazilian system uses direct alerts of damage, without
      the aid of baseline values. The strength of the Brazilian form of monitoring is
      the possibility of generating an information network with the effective
      participation of many actors from the monitored area. A network constituted by
      highly qualified members, as proposed elsewhere, is too complex and unrealistic
      in Brazil and in many other countries. In conclusion, the Brazilian monitoring
      system is flexible and can be adjusted to the Brazilian reality over the next
      years, as a response to the ever growing experience in monitoring. It also meets
      the demands of the Brazilian society for transparency, rational use of resources,
      opportunity for national companies, and food and environmental biosafety. 

PMID- 24659219
TI  - Factors associated with mental health service use among Latino and Asian
      Americans.
AB  - Literature concur that there is a disparity between epidemiological prevalence
      and mental health services (MHS) utilization rates for Latino and Asian
      Americans. This study adapted the behavioral model of health service use to
      examine factors associated with MHS use among Latino and Asian Americans. The
      model consists of predisposing, enabling, and need factors. This study used the
      National Latino and Asian American Study data, including six ethnic groups. The
      outcome measure for this study was the use of MHS in the past 12 months. Age,
      sex, and education predicted higher odds of MHS use among Latinos, none of which
      were significant among Asians. Needs factors were strongly associated with higher
      odds of MHS use among Latinos and Asians.

PMID- 24659220
TI  - Association of promoter genetic variants in interleukin-10 and Kawasaki disease
      with coronary artery aneurysms.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute, self-limited vasculitis in infants
      and young children. Interleukin-10 (IL-10) is a potent cytokine that exerts
      pleiotropic effects on immunoregulation and inflammation. Elevated IL-10 serum
      levels have been reported in the KD patients. METHODS: In this study, we
      investigated whether IL-10 genetic polymorphisms contribute to coronary artery
      aneurysm (CAA) development among KD patients in Taiwan. A total of 58 KD patients
      with CAA and 277 unrelated healthy children matched for sex and age were enrolled
      for this study. RESULTS: Higher G allele frequencies of IL-10 at -1082 position
      were observed in KD patients with CAA compared to the controls (P = 0.016, OR:
      2.86, 95% CI, 1.17-6.98). In addition, higher IL-10 GCC haplotype frequencies
      were also observed in KD patients with CAA (P = 0.016, OR: 2.85, 95% CI, 1.17
      6.98). CONCLUSION: Our data support the possibility that IL-10 gene polymorphisms
      may be related with CAA development of KD in Taiwanese population.

PMID- 24659221
TI  - Oxygen adsorption characteristics on hybrid carbon and boron-nitride nanotubes.
AB  - In this work, first-principles density functional theory (DFT) is used to predict
      oxygen adsorption on two types of hybrid carbon and boron-nitride nanotubes
      (CBNNTs), zigzag (8,0), and armchair (6,6). Although the chemisorption of O2 on
      CBNNT(6,6) is calculated to be a thermodynamically unfavorable process, the
      binding of O2 on CBNNT(8,0) is found to be an exothermic process and can form
      both chemisorbed and physisorbed complexes. The CBNNT(8,0) has very different O2
      adsorption properties compared with pristine carbon nanotubes (CNTs) and boron
      nitride nanotube (BNNTs). For example, O2 chemisorption is significantly enhanced
      on CBNNTs, and O2 physisorption complexes also show stronger binding, as compared
      to pristine CNTs or BNNTs. Furthermore, it is found that the O2 adsorption is
      able to increase the conductivity of CBNNTs. Overall, these properties suggest
      that the CBNNT hybrid nanotubes may be useful as a gas sensor or as a catalyst
      for the oxygen reduction reaction.

PMID- 24659222
TI  - Adiposopathy, "sick fat," Ockham's razor, and resolution of the obesity paradox.
AB  - Among lean populations, cardiovascular disease (CVD) is rare. Among those with
      increased adiposity, CVD is the commonest cause of worldwide death. The "obesity
      paradox" describes seemingly contrary relationships between body fat and
      health/ill-health. Multiple obesity paradoxes exist, and include the anatomic
      obesity paradox, physiologic obesity paradox, demographic obesity paradox,
      therapeutic obesity paradox, cardiovascular event/procedure obesity paradox, and
      obesity treatment paradox. Adiposopathy ("sick fat") is defined as
      adipocyte/adipose tissue dysfunction caused by positive caloric balance and
      sedentary lifestyle in genetically and environmentally susceptible individuals.
      Adiposopathy contributes to the commonest metabolic disorders encountered in
      clinical practice (high glucose levels, high blood pressure, dyslipidemia, etc.),
      all major CVD risk factors. Ockham's razor is a principle of parsimony which
      postulates that among competing theories, the hypothesis with the fewest
      assumptions is the one best selected. Ockham's razor supports adiposopathy as the
      primary cause of most cases of adiposity-related metabolic diseases, which in
      turn helps resolve the obesity paradox. 

PMID- 24659223
TI  - Elbow rehabilitation in traumatic pathology.
AB  - The elbow, intermediate joint of the upper limb, frequently undergoes to
      pathological events and is especially prone to stiffness. Rehabilitation plays an
      important role in recovering functional activities. For the rehabilitation team,
      this goal always represents a challenge, as the treatment has to be continuously
      modeled and calibrated on the needs of the individual patient, even many times
      during the same rehabilitation cycle. Containing the effects of immobilization,
      avoiding to excessively stress the healing tissues, satisfying specific clinical
      criteria before moving to the next rehabilitation stage, basing the
      rehabilitation plan on up-to-date clinical and scientific data that can be
      adapted to each patient and to his/her needs are the basic principles of the
      rehabilitation plan, which can be chronologically grouped into four
      rehabilitation stages. After summarizing the general principles of elbow
      treatment, the specific principles of rehabilitation after elbow fractures and
      elbow instability are presented, and then the rehabilitative approach to the most
      frequent and feared pathological conditions of the elbow, namely stiffness, is
      described. 

PMID- 24659224
TI  - Food dropping as a food transfer mechanism among western  lowland gorillas in
      Moukalaba-Doudou National Park, Gabon.
AB  - In this paper, I describe the food-dropping behavior of western lowland gorillas
      observed in Moukalaba- Doudou National Park, Gabon. I collected observational
      data of gorillas eating in trees, and recorded whether any individuals were
      positioned under the same tree. In 22 of the 24 cases of individuals being
      present under a tree, I observed the gorilla in a tree dropping food to the
      individual below. In most cases, the recipient was a silverback or an elder half
      sibling of the dropper. The dropper's elder full-sibling was never a recipient.
      The food-dropping behavior of Moukalaba western lowland gorillas is likely due to
      a combination of factors: their frugivory, arboreality, large body size, and the
      scarcity of terrestrial herbs. It is difficult for multiple gorillas to
      simultaneously feed in the same tree. Under such limitations, younger gorillas
      face difficulties in defending their feeding patches from older individuals.
      Nearly 90 % of the recipients were older than the food droppers. Furthermore,
      food droppers were significantly younger than non-food droppers who
      simultaneously fed on the same tree, and most-food recipients were significantly
      older than least-food recipients on the ground. Food dropping may, therefore, be
      a tactic employed by younger gorillas to defend a feeding site from older
      individuals. This study suggests that food dropping may reduce feeding contest
      competition in a gorilla group in Moukalaba. This is a preliminary study that
      indicates that food dropping may be intentionally used as a way to reduce feeding
      competition; nevertheless, further studies are needed.

PMID- 24659225
TI  - Outcomes following cardiac catheterization after congenital heart surgery.
AB  - OBJECTIVES: Describe outcomes following unplanned cardiac catheterization after
      congenital heart surgery. BACKGROUND: Utility of cardiac catheterization
      following congenital heart surgery is relatively understudied. METHODS:
      Retrospective study examining demographics, indications, and outcomes of
      unplanned cardiac catheterization after congenital heart surgery at a single
      institution. RESULTS: Between October 2004 and April 2011, 120 patients underwent
      150 unplanned postoperative cardiac catheterizations. Median day of
      catheterization was postoperative day 20 (range 1-269 days). Survival 30 days
      postcatheterization was 85%; overall survival to hospital discharge was 72%.
      Indications for catheterization: 63 for hemodynamic evaluation, 46 for likely
      intervention, and 41 for assessment of surgical repair. Of the 150
      hemodynamic/interventional catheterizations, 103 (69%) were associated with a
      change in clinical management: 59 trans-catheter interventions, 22 re-operations,
      11 changes in medication, six changes in surgical plan, and five withdrawals of
      support. Complications included hemorrhage in two patients, supraventricular
      tachycardia in two patients, and transient complete heart block requiring
      cardiopulmonary resuscitation in one patient. CONCLUSIONS: Cardiac
      catheterization following congenital heart surgery may enable important
      diagnostic and therapeutic changes in clinical and surgical management.
      Complications were rare.

PMID- 24659227
TI  - Central failures of lightweight monofilament polyester mesh   causing hernia
      recurrence: a cautionary note.
AB  - INTRODUCTION: Uncoated, lightweight, macroporous,monofilament mesh has been shown
      to demonstrate improved bacterial clearance, better tissue integration,reduced
      foreign body response, and less chronic pain with equivalent durability for
      hernia repair. These findings led us to use a new lightweight monofilament
      polyester mesh (Parietex TCM, Covidien). Here, we report our experience with this
      mesh in open incisional hernia repair. METHODS: Patients undergoing incisional
      hernia repair with Parietex TCM were retrospectively identified within our
      prospectively maintained database. Patient demographics,operative
      characteristics, and follow-up were reviewed. Outcome parameters included 90-day
      wound morbidity and hernia recurrence. RESULTS: In 2011, 36 patients (mean age
      56.8; mean BMI32.4 kg/m2) underwent open incisional hernia repair with
      retrorectus mesh placement by two surgeons (MJR, YWN) at Case Medical Center.
      Anterior and posterior fascial closure was achieved in all cases. Wound morbidity
      included seven surgical site occurrences: four superficial infections that
      resolved with antibiotics, one wound dehiscence requiring wet-to-dry packing, and
      two seromas that resolved without intervention. With a mean follow-up of 13
      months, 8 (22%) recurrences have occurred. On reoperation, 7 (19%) of these
      patients had mechanical failure or fracturing of the mesh. No confounding
      variables were identified by univariate analysis of patient
      demographics,operative characteristics, or wound morbidity. CONCLUSION:
      Lightweight monofilament polyester mesh (Parietex TCM) appears to have a high
      incidence of mechanical failure in the context of open incisional hernia repair.
      While this limitation may ultimately be revealed asa weakness of all lightweight
      mesh, surgeons should be aware that these failures have already been documented.

PMID- 24659226
TI  - Atypical spindle cell lipoma: a clinicopathologic, immunohistochemical, and
      molecular study emphasizing its relationship to classical spindle cell lipoma.
AB  - We studied a series of spindle cell lipomas arising in atypical sites and showing
      unusual morphologic features (which we called atypical spindle cell lipoma) to
      assess if these lesions have the same chromosomal alterations as classical
      spindle cell lipoma but different from those found in atypical lipomatous
      tumor/well-differentiated liposarcoma. We investigated alterations of different
      genes in the 13q14 region and the amplification status of the MDM2 and CDK4 genes
      at 12q14-15 by multiplex ligation-dependent probe amplification (MLPA) and
      fluorescence in situ hybridization (FISH) analysis. In the atypical spindle cell
      lipomas, MLPA revealed deletions in the two nearest flanking genes of RB1 (ITM2B
      and RCBTB2) and in multiple important exons of RB1. In contrast, in classical
      spindle cell lipomas, a less complex loss of RB1 exons was found but no deletion
      of ITM2B and RCBTB2. Moreover, MLPA identified a deletion of the DLEU1 gene, a
      finding which has not been reported earlier. We propose an immunohistochemical
      panel for lipomatous tumors which comprises of MDM2, CDK4, p16, Rb, which we have
      found useful in discriminating between atypical or classical spindle cell lipomas
      and other adipocytic neoplasms, especially atypical lipomatous tumor/well
      differentiated liposarcoma. Our findings strengthen the link between atypical
      spindle cell lipoma and classical spindle cell lipoma, and differentiate them
      from atypical lipomatous tumor/well-differentiated liposarcoma.

PMID- 24659228
TI  - Analysis of a support group for children of parents with mental illnesses:
      managing stressful situations.
AB  - We report an ethnographic analysis of a psycho-education and peer-support program
      for school-aged children of parents with mental illnesses. We conducted a
      critical discourse analysis of the program manual and observed group interactions
      to understand whether children shared program goals predetermined by adults, and
      how, or if, the intervention was responsive to their needs. Children were
      expected to learn mental illness information because "knowledge is power," and to
      express difficult feelings about being a child of a mentally ill parent that was
      risky. Participants used humor to manage group expectations, revealing how they
      made sense of their parents' problems, as well as their own. Suggestions are made
      for determining good mental health literacy based on children's preferences for
      explaining circumstances in ways they find relevant, and for supporting
      children's competencies to manage relationships that are important to them. 

PMID- 24659229
TI  - [Yoko Ono. Half-A-Wind Show. Retrospective: Yoko Ono in the Guggenheim Museum
      Bilbao (14 March 2014 - 31 August 2014)].

PMID- 24659231
TI  - New infrared transmitting material via inverse vulcanization of elemental sulfur
      to prepare high refractive index polymers.
AB  - Polymers for IR imaging: The preparation of high refractive index polymers (n =
      1.75 to 1.86) via the inverse vulcanization of elemental sulfur is reported. High
      quality imaging in the near (1.5 MUm) and mid-IR (3-5 MUm) regions using high
      refractive index polymeric lenses from these sulfur materials was demonstrated. 

PMID- 24659230
TI  - Primary immunodeficiency disorders in Iran: update and new insights from the
      third report of the national registry.
AB  - BACKGROUND: Primary immunodeficiency disorders (PID) are a group of heterogeneous
      disorders mainly characterized by severe and recurrent infections and increased
      susceptibility to malignancies, lymphoproliferative and autoimmune conditions.
      National registries of PID disorders provide epidemiological data and increase
      the awareness of medical personnel as well as health care providers. METHODS:
      This study presents the demographic data and clinical manifestations of Iranian
      PID patients who were diagnosed from March 2006 till the March of 2013 and were
      registered in Iranian PID Registry (IPIDR) after its second report of 2006.
      RESULTS: A total number of 731 new PID patients (455 male and 276 female) from 14
      medical centers were enrolled in the current study. Predominantly antibody
      deficiencies were the most common subcategory of PID (32.3 %) and were followed
      by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number,
      function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2
      %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %),
      defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe
      combined immunodeficiency was the most common disorder (21.1 %). Other prevalent
      disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7
      %), and selective IgA deficiency (7.5 %). CONCLUSIONS: Registration of Iranian
      PID patients increased the awareness of medical community of Iran and developed
      diagnostic and therapeutic techniques across more parts of the country. Further
      efforts must be taken by increasing the coverage of IPIDR via electronically
      registration and gradual referral system in order to provide better estimation of
      PID in Iran and reduce the number of undiagnosed cases.

PMID- 24659233
TI  - Resveratrol inhibits glucose-induced migration of vascular smooth muscle cells
      mediated by focal adhesion kinase.
AB  - SCOPE: Diabetes is a critical factor for atherosclerosis, as hyperglycemia
      induces vascular smooth muscle cell (VSMC) proliferation and migration and
      subsequently contributes to the formation of atherosclerotic lesions. This study
      investigates whether resveratrol plays a regulatory role in the proliferation and
      migration of VSMCs under high glucose induction to imitate a hyperglycemic
      condition. METHODS AND RESULTS: Resveratrol inhibited the migration of VSMCs in
      the wound-healing assay and the formation of lamellipodia and filopodia as
      assessed by atomic force microscopy scanning. Resveratrol suppressed the mRNA
      expression of c-Src, Rac1, cdc42, IRS-1, MEKK1, MEKK4, and mitogen-activated
      protein kinase along with the protein levels of c-Src, p-Src, and cdc42 in VSMCs.
      Resveratrol decreased the level of p-FAK protein under normal glucose conditions.
      Resveratrol could inhibit the activities of matrix metalloproteinase (MMP) 2 and
      MMP 9 as shown by zymography. Moreover, resveratrol also regulated the mitogen
      activated protein kinase pathway and MMP activities of VSMC migration under the
      high glucose condition. CONCLUSION: The antimigratory effects of resveratrol by
      reduced MMP expression through the inhibition of Rac1, p-FAK, and lamellipodia
      formation and the activation of p-AKT and p-ERK1/2 suggest that resveratrol is a
      potential compound for the treatment of vascular diseases via the regulation of
      VSMC migration.

PMID- 24659232
TI  - Murine Notch1 is required for lymphatic vascular morphogenesis during
      development.
AB  - BACKGROUND: The transmembrane receptor Notch1 is a critical regulator of arterial
      differentiation and blood vessel sprouting. Recent evidence shows that functional
      blockade of Notch1 and its ligand, Dll4, leads to postnatal lymphatic defects in
      mice. However, the precise role of the Notch signaling pathway in lymphatic
      vessel development has yet to be defined. Here we show the developmental role of
      Notch1 in lymphatic vascular morphogenesis by analyzing lymphatic endothelial
      cell (LEC)-specific conditional Notch1 knockout mice crossed with an inducible
      Prox1CreER(T2) driver. RESULTS: LEC-specific Notch1 mutant embryos exhibited
      enlarged lymphatic vessels. The phenotype of lymphatic overgrowth accords with
      increased LEC sprouting from the lymph sacs and increased filopodia formation.
      Furthermore, cell death was significantly reduced in Notch1-mutant LECs, whereas
      proliferation was increased. RNA-seq analysis revealed that expression of
      cytokine/chemokine signaling molecules was upregulated in Notch1-mutant LECs
      isolated from E15.5 dorsal skin, whereas VEGFR3, VEGFR2, VEGFC, and Gja4
      (Connexin 37) were downregulated. CONCLUSIONS: The lymphatic phenotype of LEC
      specific conditional Notch1 mouse mutants indicates that Notch activity in LECs
      controls lymphatic sprouting and growth during development. These results provide
      evidence that similar to postnatal and pathological lymphatic vessel formation,
      the Notch signaling pathway plays a role in inhibiting developmental
      lymphangiogenesis.

PMID- 24659234
TI  - Test-retest reliability of peripheral arterial tonometry in the metabolic
      syndrome.
AB  - Endothelial dysfunction is an important contributor to atherosclerosis and
      cardiovascular disease. However, routine assessment via angiography or flow
      mediated dilation is difficult due to technical limitations. Peripheral arterial
      tonometry (PAT) is a promising alternative method for non-invasive assessment of
      endothelial dysfunction. This study assessed the test-retest reliability of PAT
      in adults with the metabolic syndrome (n = 20) and provides sample size and power
      estimates for study design. Participants completed five PAT tests each separated
      by 1 week. The PAT-derived reactive hyperaemia index (RHI) showed robust
      repeatability (intra-class correlation = 0.74). A parallel-arm study powered at
      0.90 would require 22 participants to detect an absolute change in RHI of 0.40
      units (equal to ~25% change in this sample), whereas a crossover study would
      require 12 participants. In conclusion, we have demonstrated that PAT can be used
      to assess endothelial dysfunction in adults with the metabolic syndrome as
      reliably as in healthy samples. 

PMID- 24659235
TI  - Chemotactic responses of neural stem cells to SDF-1alpha correlate closely with
      their differentiation status.
AB  - Chemotaxis of neural stem/progenitor cells (NSCs) is regulated by a variety of
      factors, and much effort has been devoted to the delineation of factors that are
      involved in NSC migration. However, the relationship between NSC chemotactic
      migration and differentiation remains uncharacterized. In the present study, by
      comparing the transfilter migration rate, single-cell migration speed, and
      directional efficiency of NSCs in stromal cell-derived factor-1 alpha (SDF
      1alpha)-induced Boyden chamber and Dunn chamber chemotaxis assays, we demonstrate
      that NSCs in varying differentiation stages possess different migratory capacity.
      Furthermore, F-actin microfilament reorganization upon stimulation varies greatly
      among separate differentiation states. We show that signaling pathways involved
      in NSC migration, such as PI3K/Akt and mitogen-activated protein kinase (MAPK)
      (ERK1/2, JNK, and p38 MAPK) pathways, are differentially activated by SDF-1alpha
      among each NSC differentiation stages, and the extent to which these pathways
      participate in cell chemotaxis exhibits a differentiation stage-dependent manner.
      Taken together, these results suggest that the differentiation of NSCs influences
      their chemotactic responses to SDF-1alpha, providing new insight into the
      optimization of the therapeutic efficacy of NSCs for neural regeneration and
      nerve repair after injury.

PMID- 24659236
TI  - A randomized, double-blind, placebo-controlled study of rebamipide for gastric
      mucosal injury taking aspirin with or without clopidogrel.
AB  - INTRODUCTION: Antithrombotic drugs, such as low-dose aspirin (LDA) and
      clopidogrel, can cause upper gastrointestinal complications. AIM: The goal of the
      present study was to investigate whether a mucosal-protective agent, rebamipide,
      could prevent gastric mucosal injuries induced by LDA with or without clopidogrel
      in healthy subjects. MATERIALS AND METHODS: A randomized, double-blind, placebo
      controlled trial was performed with 32 healthy male volunteers. Subjects were
      randomly assigned to a 14-day course of one of the following regimens: group A,
      placebo (tid) + LDA; group B, rebamipide (100 mg tid) + LDA (100 mg once-daily);
      group C, placebo + LDA + clopidogrel (75 mg once-daily); or group D, rebamipide +
      LDA + clopidogrel. The grade of gastric mucosal injuries was evaluated by
      esophagogastroduodenoscopy before and after dosing (on day 0 and day 14), and the
      grade of gastric mucosal injury was assessed according to the modified Lanza
      score. Subjective symptoms were assessed using the Gastrointestinal Symptom
      Rating Scale (GSRS). A rapid urease test was performed on day 0, and blood tests
      were performed on day 0 and day 14. RESULTS: Rebamipide significantly inhibited
      gastric mucosal injury induced by LDA alone or by LDA plus clopidogrel when
      compared with placebo in healthy subjects. GSRS score and hemoglobin level were
      not significantly different among the four groups. CONCLUSIONS: Rebamipide is
      useful for the primary prevention of gastric mucosal injury induced by LDA alone
      or by LDA plus clopidogrel in healthy subjects.

PMID- 24659237
TI  - Recurrence of cancer after endoscopic ablation of Barrett's esophagus: is the
      elephant in the room...persistent ongoing reflux?

PMID- 24659238
TI  - An overview of magnetic resonance enterography for Crohn's disease.
AB  - Magnetic resonance enterography (MRE) is a relatively new imaging modality that
      has shown promise for diagnosing, staging, and monitoring Crohn's disease (CD)
      and its complications while avoiding exposure to ionizing radiation. In addition
      to clinical implications, MRE has the potential to be used as an objective
      measure of disease activity for clinical trials. We provide the rationale for
      MRE, indications for its use, and an overview of the typical procedure and common
      findings for institutions who want to begin or refine the use of MRE for CD.

PMID- 24659239
TI  - Influence of age at entry and level of concentrate feeding  on growth and carcass
      characteristics of feedlot-finished  Tanzanian long-fat-tailed sheep.
AB  - A 4*3 factorial experiment was carried out to evaluate the effects of age at
      entry to feedlot (AEF) and levels of concentrate feeding (LCF) on body weight
      gain, feed utilization and killing out characteristics of Tanzanian long-fat-
      tailed castrate sheep. The AEF points were 9, 12, 15 and 18 months, designated as
      AEF9, AEF12, AEF15 and AEF18, and the LCF were 50, 75 and 100 % of ad libitum
      concentrate intake designated as LCF50, LCF75 and LCF100, the last representing
      ad libitum concentrate intake with 10 % refusal rate. Grass hay as basal diet was
      offered ad libitum to each sheep. Daily feed intake and weekly live weight were
      recorded for a period of 84 days. Animals were slaughtered and carcass and non
      carcass parameters were recorded. Dry matter intake (DMI) of hay decreased while
      DMI of concentrate increased (p<0.01) with increasing LCF. Daily gain in high
      level (LCF100) was 93.1 g/day, almost twofold higher than that in low level
      (LCF50) of feeding (39 g/day). Overall dressing percentage ranged from 40.7 to
      46.5% and increased with increasing AEF. The proportion of carcass bone decreased
      (p<0.05) with increasing AEF while that of fat increased (p<0.05) with increasing
      LCF. Age at entry * level of concentrate feeding interaction was detected for
      DMI, feed conversion ratio (FCR), slaughter body weight (SBW), muscle/bone ratio
      and bone (as % cold carcass weight (CCW)), but the effect was not regular.
      Entering fattening at 18th month seems too late, hence to get in the shortest
      time the highest output slaughter and carcass weights, fattening should start
      latest at 15 month.

PMID- 24659240
TI  - Amyloidogenic alpha-synuclein seeds do not invariably induce rapid, widespread
      pathology in mice.
AB  - In order to further evaluate the parameters whereby intracerebral administration
      of recombinant alpha-synuclein (alphaS) induces pathological phenotypes in mice,
      we conducted a series of studies where alphaS fibrils were injected into the
      brains of M83 (A53T) and M47 (E46K) alphaS transgenic (Tg) mice, and non
      transgenic (nTg) mice. Using multiple markers to assess alphaS inclusion
      formation, we find that injected fibrillar human alphaS induced widespread
      cerebral alphaS inclusion formation in the M83 Tg mice, but in both nTg and M47
      Tg mice, induced alphaS inclusion pathology is largely restricted to the site of
      injection. Furthermore, mouse alphaS fibrils injected into nTg mice brains also
      resulted in inclusion pathology restricted to the site of injection with no
      evidence for spread. We find no compelling evidence for extensive spread of
      alphaS pathology within white matter tracts, and we attribute previous reports of
      white matter tract spreading to cross-reactivity of the alphaS pSer129/81A
      antibody with phosphorylated neurofilament subunit L. These studies suggest that,
      with the exception of the M83 Tg mice which appear to be uniquely susceptible to
      induction of inclusion pathology by exogenous forms of alphaS, there are
      significant barriers in mice to widespread induction of alphaS pathology
      following intracerebral administration of amyloidogenic alphaS.

PMID- 24659241
TI  - TDP-43 is a key player in the clinical features associated with Alzheimer's
      disease.
AB  - The aim of this study was to determine whether the TAR DNA-binding protein of 43
      kDa (TDP-43) has any independent effect on the clinical and neuroimaging features
      typically ascribed to Alzheimer's disease (AD) pathology, and whether TDP-43
      pathology could help shed light on the phenomenon of resilient cognition in AD.
      Three-hundred and forty-two subjects pathologically diagnosed with AD were
      screened for the presence, burden and distribution of TDP-43. All had been
      classified as cognitively impaired or normal, prior to death. Atlas-based
      parcellation and voxel-based morphometry were used to assess regional atrophy on
      MRI. Regression models controlling for age at death, apolipoprotein epsilon4 and
      other AD-related pathologies were utilized to explore associations between TDP-43
      and cognition or brain atrophy, stratified by Braak stage. In addition, we
      determined whether the effects of TDP-43 were mediated by hippocampal sclerosis.
      One-hundred and ninety-five (57%) cases were TDP-positive. After accounting for
      age, apolipoprotein epsilon4 and other pathologies, TDP-43 had a strong effect on
      cognition, memory loss and medial temporal atrophy in AD. These effects were not
      mediated by hippocampal sclerosis. TDP-positive subjects were 10* more likely to
      be cognitively impaired at death compared to TDP-negative subjects. Greater
      cognitive impairment and medial temporal atrophy were associated with greater TDP
      43 burden and more extensive TDP-43 distribution. TDP-43 is an important factor
      in the manifestation of the clinico-imaging features of AD. TDP-43 also appears
      to be able to overpower what has been termed resilient brain aging. TDP-43
      therefore should be considered a potential therapeutic target for the treatment
      of AD.

PMID- 24659242
TI  - Perceptions of risk among childhood and young adult cancer survivors who smoke.
AB  - PURPOSE: Despite the fact that childhood and young adult cancer survivors are at
      increased risk for chronic health problems as a result of their cancer treatment,
      many use tobacco, thereby increasing their risks. Perceptions of risk related to
      tobacco use can be targeted for interventions aimed at improving health behaviors
      for childhood, adolescent, and young adult cancer survivors. Understanding the
      covariates of perceptions of health risks among young adult survivors who smoke
      will help to determine targets for intervention. METHOD: Three hundred seventy
      four participants who were diagnosed with cancer prior to age 35, currently
      between 18 and 55 years of age, and current smokers were recruited as part of a
      larger smoking cessation study, Partnership for Health-2 (PFH-2). Data were
      collected by telephone survey. RESULTS: Overall, women had the highest perception
      of risk for serious health problems, a second cancer, and heart problems.
      Additionally, those participants who were dependent on nicotine endorsed that
      they were at higher risk of serious health problems and second cancers, but not
      heart problems. Finally, Hodgkin lymphoma survivors reported that they were at
      increased risk for second cancers and heart problems compared to their "healthy"
      peers. CONCLUSION: Young adult cancer survivors who smoke correctly perceived
      some of their increased health risks. Additional motivation and education is
      needed for those young adult cancer survivors who perceive their increased health
      risks yet continue to smoke. Further education is needed for young survivors so
      they have a fully appropriate sense of risk, especially as it relates to their
      tobacco use.

PMID- 24659243
TI  - Use of and spending on supportive care medications among Medicare beneficiaries
      with cancer.
AB  - PURPOSE: The study objective was to provide population-based estimates of
      supportive care medication (SCM) use among Medicare beneficiaries with cancer and
      determine factors related to SCM receipt. METHODS: This retrospective cohort
      study of community-based Medicare beneficiaries used the Medicare Current
      Beneficiary Survey (1997-2007). Dependent variables comprised use and spending on
      SCMs for three medication classes: opioids, antidepressants/sedative/hypnotics
      (ASH), and antiemetics. Independent variables of interest were supplemental
      insurance coverage, cancer site, and treatment. Multivariate models determined
      factors affecting receipt of, and spending on, SCMs. We also compared SCM use and
      spending among beneficiaries with and without cancer in order to understand what
      portion of SCM use and spending could be attributed to cancer as opposed to other
      comorbid conditions. RESULTS: A total of 1,836 Medicare beneficiaries with cancer
      and 9,898 beneficiaries without cancer were eligible for the study. Beneficiaries
      with cancer were more likely to receive opioids, ASH, and antiemetics compared to
      non-cancer beneficiaries. Adjusted annual payments for antiemetics were on
      average $637 higher in with cancer versus without cancer (p<0.01), while ASH
      payments were $184 lower (p<0.01). Opioid spending was similar among cancer and
      non-cancer users. Relative to colon cancer, beneficiaries with prostate cancer
      were least likely to receive any of the three SCM classes. Receipt of
      antineoplastic treatment increased the probability of use of all three classes of
      SCMs. Insurance coverage did not influence the use of or spending on opioids or
      antiemetics, but was associated with both outcomes for ASH. The use of all three
      SCM classes was significantly lower during years before Part D implementation of
      the new Medicare Part D prescription drug benefit and was higher after
      implementation of Part D. CONCLUSION: This study provides population-based
      information on SCM use among Medicare beneficiaries with cancer. Cancer site and
      treatment modality were important predictors of SCM use.

PMID- 24659244
TI  - A European patient record study on diagnosis and treatment of chemotherapy
      induced anaemia.
AB  - PURPOSE: Patients with cancer frequently experience chemotherapy-induced anaemia
      (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron
      supplementation and blood transfusions are available therapies. This study
      evaluated routine practice in CIA management. METHODS: Medical oncologists and/or
      haematologists from nine European countries (n=375) were surveyed on their last
      five cancer patients treated for CIA (n=1,730). Information was collected on
      tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum
      ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies.
      RESULTS: Diagnostic tests and therapies for CIA varied across Europe. Anaemia and
      iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements.
      TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb <= 10
      g/dL, including 15% with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin
      <= 100 ng/mL) were detected in 42% of evaluated patients. ESA was used in 63%of
      patients, blood transfusions in 52 % and iron supplementation in 31% (74% oral,
      26% intravenous iron). Only 30% of ESA-treated patients received a combination of
      ESA and iron supplementation. Blood transfusions formed part of a regular anaemia
      treatment regimen in 76% of transfused patients. Management practices were
      similar in 2009 and 2011. CONCLUSION: Management of anaemia and iron status in
      patients treated for CIA varies substantially across Europe. Iron status is only
      assessed in half of the patients. In contrast to clinical evidence, iron
      treatment is under utilised and mainly based on oral iron supplementation.
      Implementation of guidelines needs to be increased to minimize the use of blood
      transfusions.

PMID- 24659245
TI  - Coilin association with Box C/D scaRNA suggests a direct role for the Cajal body
      marker protein in scaRNP biogenesis.
AB  - Spliceosomal small nuclear ribonucleoproteins (snRNPs) are enriched in the Cajal
      body (CB). Guide RNAs, known as small Cajal body-specific RNAs (scaRNAs), direct
      modification of the small nuclear RNA (snRNA) component of the snRNP. The protein
      WRAP53 binds a sequence motif (the CAB box) found in many scaRNAs and the RNA
      component of telomerase (hTR) and targets these RNAs to the CB. We have
      previously reported that coilin, the CB marker protein, associates with certain
      non-coding RNAs. For a more comprehensive examination of the RNAs associated with
      coilin, we have sequenced the RNA isolated from coilin immunocomplexes. A
      striking preferential association of coilin with the box C/D scaRNAs 2 and 9,
      which lack a CAB box, was observed. This association varied by treatment
      condition and WRAP53 knockdown. In contrast, reduction of WRAP53 did not alter
      the level of coilin association with hTR. Additional studies showed that coilin
      degrades/processes scaRNA 2 and 9, associates with active telomerase and can
      influence telomerase activity. These findings suggest that coilin plays a novel
      role in the biogenesis of box C/D scaRNPs and telomerase. 

PMID- 24659246
TI  - Seasonal differences in jump performance in the Svalbard rock ptarmigan (Lagopus
      muta hyperborea).
AB  - Fat storage is essential to the survival of many bird species, providing energy
      reserves, but can have an effect on locomotor performance with an associated
      potential increase in predation risk. In particular, the ability to initiate
      flight through jumping is critical to predator avoidance and may be influenced by
      changes in body mass (Mb). Here we investigate seasonal differences in the jump
      take-off performance of high Arctic Svalbard rock ptarmigan (Lagopus muta
      hyperborea) resulting from around a 50% increase in Mb during winter as a result
      of fat deposition. Using force-plate data and videography, we reveal that, in the
      absence of alterations to take-off angle, winter Svalbard rock ptarmigan are
      unable to increase hind-limb power output during jumping to compensate for their
      increased Mb. As a result, peak take-off velocity is reduced by 42% and jump
      duration is also extended during winter. The consequences of reduced jumping
      performance upon Svalbard ptarmigan during winter may be relatively small given
      their low risk of predation during this season. It may be, however, that the
      observed reduction in jumping performance when fat may contribute to the sub
      maximal pattern of fat acquisition observed in other bird species. 

PMID- 24659247
TI  - Assisted protein folding at low temperature: evolutionary adaptation of the
      Antarctic fish chaperonin CCT and its client proteins.
AB  - Eukaryotic ectotherms of the Southern Ocean face energetic challenges to protein
      folding assisted by the cytosolic chaperonin CCT. We hypothesize that CCT and its
      client proteins (CPs) have co-evolved molecular adaptations that facilitate CCT
      CP interaction and the ATP-driven folding cycle at low temperature. To test this
      hypothesis, we compared the functional and structural properties of CCT-CP
      systems from testis tissues of an Antarctic fish, Gobionotothen gibberifrons
      (Lonnberg) (habitat/body T = -1.9 to +2 degrees C), and of the cow (body T = 37
      degrees C). We examined the temperature dependence of the binding of denatured
      CPs (beta-actin, beta-tubulin) by fish and bovine CCTs, both in homologous and
      heterologous combinations and at temperatures between -4 degrees C and 20 degrees
      C, in a buffer conducive to binding of the denatured CP to the open conformation
      of CCT. In homologous combination, the percentage of G. gibberifrons CCT bound to
      CP declined linearly with increasing temperature, whereas the converse was true
      for bovine CCT. Binding of CCT to heterologous CPs was low, irrespective of
      temperature. When reactions were supplemented with ATP, G. gibberifrons CCT
      catalyzed the folding and release of actin at 2 degrees C. The ATPase activity of
      apo-CCT from G. gibberifrons at 4 degrees C was ~2.5-fold greater than that of
      apo-bovine CCT, whereas equivalent activities were observed at 20 degrees C.
      Based on these results, we conclude that the catalytic folding cycle of CCT from
      Antarctic fishes is partially compensated at their habitat temperature, probably
      by means of enhanced CP-binding affinity and increased flexibility of the CCT
      subunits. 

PMID- 24659249
TI  - Various applications of TALEN- and CRISPR/Cas9-mediated homologous recombination
      to modify the Drosophila genome.
AB  - Modifying the genomes of many organisms is becoming as easy as manipulating DNA
      in test tubes, which is made possible by two recently developed techniques based
      on either the customizable DNA binding protein, TALEN, or the CRISPR/Cas9 system.
      Here, we describe a series of efficient applications derived from these two
      technologies, in combination with various homologous donor DNA plasmids, to
      manipulate the Drosophila genome: (1) to precisely generate genomic deletions;
      (2) to make genomic replacement of a DNA fragment at single nucleotide
      resolution; and (3) to generate precise insertions to tag target proteins for
      tracing their endogenous expressions. For more convenient genomic manipulations,
      we established an easy-to-screen platform by knocking in a white marker through
      homologous recombination. Further, we provided a strategy to remove the unwanted
      duplications generated during the "ends-in" recombination process. Our results
      also indicate that TALEN and CRISPR/Cas9 had comparable efficiency in mediating
      genomic modifications through HDR (homology-directed repair); either TALEN or the
      CRISPR/Cas9 system could efficiently mediate in vivo replacement of DNA fragments
      of up to 5&emsp14;kb in Drosophila, providing an ideal genetic tool for
      functional annotations of the Drosophila genome. 

PMID- 24659248
TI  - A Drosophila immune response against Ras-induced overgrowth.
AB  - Our goal is to characterize the innate immune response against the early stage of
      tumor development. For this, animal models where genetic changes in specific
      cells and tissues can be performed in a controlled way have become increasingly
      important, including the fruitfly Drosophila melanogaster. Many tumor mutants in
      Drosophila affect the germline and, as a consequence, also the immune system
      itself, making it difficult to ascribe their phenotype to a specific tissue. Only
      during the past decade, mutations have been induced systematically in somatic
      cells to study the control of tumorous growth by neighboring cells and by immune
      cells. Here we show that upon ectopic expression of a dominant-active form of the
      Ras oncogene (Ras(V12)), both imaginal discs and salivary glands are affected.
      Particularly, the glands increase in size, express metalloproteinases and display
      apoptotic markers. This leads to a strong cellular response, which has many
      hallmarks of the granuloma-like encapsulation reaction, usually mounted by the
      insect against larger foreign objects. RNA sequencing of the fat body reveals a
      characteristic humoral immune response. In addition we also identify genes that
      are specifically induced upon expression of Ras(V12). As a proof-of-principle, we
      show that one of the induced genes (santa-maria), which encodes a scavenger
      receptor, modulates damage to the salivary glands. The list of genes we have
      identified provides a rich source for further functional characterization. Our
      hope is that this will lead to a better understanding of the earliest stage of
      innate immune responses against tumors with implications for mammalian immunity. 

PMID- 24659250
TI  - Serum sialic acids levels according to the severity of liver cirrhosis.
AB  - BACKGROUND: The sialylation of serum proteins and lipids changes in liver
      diseases of different etiologies and could change the total sialic acid (TSA),
      lipid-bound SA (LSA), and free SA (FSA) levels in the sera. However, little is
      known of the relationship of serum SAs concentrations and the severity of liver
      disease. Therefore, the aim of this study was to investigate the SAs
      concentrations (TSA, LSA, and FSA) in liver cirrhosis in relation with the
      severity of liver disease. METHODS: Tested group consisted of 91 consecutive
      patients suffering from liver cirrhosis. For each patient, the Child-Pugh score
      was calculated. TSA and LSA were determined by the enzymatic method on microplate
      reader, and FSA using the thiobarbituric method. RESULTS: Among the SA forms,
      only the serum FSA level in liver cirrhosis appears to be different according to
      the severity of liver damage evaluated by the Child-Pugh score. It was the
      highest in score C, and was higher than that in scores B and A. The elevated
      levels of FSA significantly positively correlated with the Child-Pugh score.
      CONCLUSION: In conclusion, the sialylation of serum proteins and lipids changes
      in liver cirrhosis, but only the serum concentrations of FSA are stage-related
      and reflect the severity of liver disease.

PMID- 24659251
TI  - Management of hyponatremia in clinical hepatology practice.
AB  - The burden of liver disease continues to increase in the United States, with the
      epidemics of hepatitis C, alcoholic liver disease, and the coming wave of
      nonalcoholic fatty liver disease patients all contributing to a high burden of
      individuals with end-stage liver disease. The complications of cirrhosis have
      been related to portal hypertension or synthetic dysfunction with variceal
      bleeding, ascites, hepatic encephalopathy, jaundice, hepatorenal syndrome, and
      the pulmonary complications of cirrhosis being described classically. Over the
      past decade, a body of evidence has now been assembled demonstrating that
      hyponatremia is also an important complication in patients with decompensated
      cirrhosis, with recent data demonstrating that hyponatremia is an important
      prognostic indicator in those with cirrhosis [1**]. Seminal research has
      demonstrated the pathophysiologic role of the hyperdynamic circulation and
      vasodilation in those with decompensated cirrhosis that leads to many of the
      complications, including hyponatremia [2*]. Moreover, a new class of drugs, the
      vaptans, have provided important insights into the pathophysiology and potential
      therapy of those with hyponatremia and possibly in those with hyponatremia and
      cirrhotic ascites [3]. However, there are safety concerns with some drugs in this
      class. In this article, the pathophysiology of hyponatremia, clinical relevance
      to patients with decompensated cirrhosis, and management options will be
      addressed. 

PMID- 24659252
TI  - Endoscopic submucosal dissection for malignant esophageal lesions.
AB  - The incidence of esophageal cancer has been increasing while the prognosis
      remains very poor. Endoscopic submucosal dissection (ESD) was developed in Japan
      for en bloc resection of early gastric cancer with excellent results. The use of
      ESD in early squamous cell cancer (SCC) of the esophagus in Japan has been
      increasing with long-term results comparable to those in early gastric cancer.
      The use of ESD in Barrett's neoplasia in western countries has been challenged by
      the low complete resection rates and the risk of metachronous lesions from
      surrounding non-dysplastic Barrett's epithelium. Efforts to combine ESD with
      other treatment modalities such as radiofrequency ablation in Barrett's neoplasia
      and chemoradiation in SCC appear to be promising. The use of steroid therapy
      (local or systemic) has been demonstrated to prevent post-ESD stenosis, which is
      the most common complication after esophageal ESD. 

PMID- 24659254
TI  - Direct diffusion-based parcellation of the human thalamus.
AB  - To assess stable anatomical features of the human thalamus, an unbiased diffusion
      tensor parcellation approach was used to segment thalamic substructures with
      similar spatial orientation. We determined localization, size and individual
      variations of 21 thalamic clusters in a group of 63 healthy human subjects (32
      males/31 females). The laterality differences accounted for +/- 6% and gender
      differences for +/- 4% of the thalamic volume. Consecutively, five stable
      clusters in the anterior, medial, lateral and posterior thalamus were selected,
      which were common to 90% of all subjects and contained at least 10 voxels. These
      clusters could be assigned to the anteroventral nucleus (AN) group, the
      mediodorsal (MD) nucleus, the medial pulvinar (PuM), and the lateral nuclei
      group. The subcortical and cortical connectivity of these clusters revealed that:
      (1) the oblique cranio-caudal-oriented fibers of the AN cluster mainly connect to
      limbic structures, (2) the numerous dorso-frontal-oriented fibers of MD mainly
      project to the prefrontal cortex and the medial temporal lobe, (3) the fibers of
      the PuM running in parallel with the x-axis project to medio-occipital and medio
      temporal areas and connect visual areas with the hippocampus and amygdala and via
      intrathalamic pathways with medio-frontal areas, and (4) the oblique caudo
      cranial fibers of the two lateral clusters located anteriorly in the motor and
      posteriorly in the sensory thalamus are routing sensory-motor information from
      the brain stem via the internal capsule to pre- and peri-central regions of the
      cortex.

PMID- 24659253
TI  - Midpoint cell method for hybrid (MPI+OpenMP) parallelization of molecular
      dynamics simulations.
AB  - We have developed a new hybrid (MPI+OpenMP) parallelization scheme for molecular
      dynamics (MD) simulations by combining a cell-wise version of the midpoint method
      with pair-wise Verlet lists. In this scheme, which we call the midpoint cell
      method, simulation space is divided into subdomains, each of which is assigned to
      a MPI processor. Each subdomain is further divided into small cells. The
      interaction between two particles existing in different cells is computed in the
      subdomain containing the midpoint cell of the two cells where the particles
      reside. In each MPI processor, cell pairs are distributed over OpenMP threads for
      shared memory parallelization. The midpoint cell method keeps the advantages of
      the original midpoint method, while filtering out unnecessary calculations of
      midpoint checking for all the particle pairs by single midpoint cell
      determination prior to MD simulations. Distributing cell pairs over OpenMP
      threads allows for more efficient shared memory parallelization compared with
      distributing atom indices over threads. Furthermore, cell grouping of particle
      data makes better memory access, reducing the number of cache misses. The
      parallel performance of the midpoint cell method on the K computer showed
      scalability up to 512 and 32,768 cores for systems of 20,000 and 1 million atoms,
      respectively. One MD time step for long-range interactions could be calculated
      within 4.5 ms even for a 1 million atoms system with particle-mesh Ewald
      electrostatics.

PMID- 24659255
TI  - Neuronal mechanisms underlying transhemispheric diaschisis following focal
      cortical injuries.
AB  - Unilateral cortical lesions cause disturbances often spreading into the
      hemisphere contralateral to the injury. The functional alteration affecting the
      contralesional cortex is called transhemispheric diaschisis and is believed to
      contribute to neurological deficits and to processes of functional reorganization
      post-lesion. Despite the profound implications for recovery, little is known
      about the cellular mechanisms that underlie this phenomenon. In the present
      study, transhemispheric diaschisis was investigated with an in vivo-ex vivo model
      of unilateral lesions, induced by an infrared laser in rat visual cortex.
      Visually evoked cortical activity was evaluated by the expression level of the
      cellular activity marker zif268, which showed an elevation in the cortex
      contralateral to the lesion. In vitro patch-clamp recordings from layer 2/3
      pyramidal neurons revealed a shift in the excitatory-inhibitory balance in favor
      of excitability, particularly expressed in the undamaged hemisphere. Layer 5
      principal neurons displayed an increased spontaneous firing rate contralateral to
      the lesion, while cells of the injured cortex displayed a reduced firing upon
      somatic current injection. These data suggest that a cortical lesion triggers an
      enhanced neuronal activity in the hemisphere contralateral to the damage. Our
      findings constitute an important step toward the understanding of
      transhemispheric diaschisis on the cellular level.

PMID- 24659256
TI  - Altered glutamate/GABA equilibrium in aged mice cortex influences cortical
      plasticity.
AB  - Age-related molecular changes in the synapse can cause plasticity decline. We
      found an impairment of experience-dependent cortical plasticity is induced by
      short lasting sensory conditioning in aged mice. However, extending the training
      procedure from 3 to 7 days triggered plasticity in the aged cortex of the same
      range as in young mice. Additionally, GABAergic markers (GABA, GAD67, VGAT) in
      young and aged groups that showed the plastic changes were upregulated. This
      effect was absent in the aged group with impaired plasticity, while the
      expression of Vglut1 increased in all trained groups. This may reflect the
      inefficiency of inhibitory mechanisms in the aging brain used to control
      increased excitation after training and to shape proper signal to noise ratio,
      which is essential for appropriate stimuli processing. HPLC analysis showed that
      the glutamate/GABA ratio was significantly reduced in aged animals due to a
      significant decrease in glutamate level. We also observed a decreased expression
      of several presynaptic markers involved in excitatory (vesicular glutamate
      transporter-vglut2) and inhibitory (glutamic acid decarboxylase-GAD67, vesicular
      GABA transporter VGAT) transmission in the aged barrel cortex. These changes may
      weaken the plasticity potential of neurons and impede the experience-dependent
      reorganization of cortical connections. We suggest that the imbalance toward
      inhibition resulting from a decrease of glutamate content in the aging cerebral
      cortex, together with GABAergic system ineffectiveness in upregulating GABA level
      after sensory training, contributes to the impairment of learning-dependent
      cortical plasticity.

PMID- 24659257
TI  - Motion correction of multi-contrast images applied to T1and T2quantification in
      cardiac MRI.
AB  - OBJECT: The ability to manipulate image contrast and thus to obtain complementary
      information is one of the main advantages of MRI. Motion consistency within the
      whole data set is a key point in the context of multi contrast imaging. In
      cardiac and abdominal MRI, the acquisition strategy uses multiple breath-holds
      and often relies on acceleration methods that inherently suffer from a signal to
      noise ratio loss. The aim of this work is to propose a free-breathing multi
      contrast acquisition and reconstruction workflow to improve image quality and the
      subsequent data analysis. MATERIALS AND METHODS: We extended a previously
      proposed motion-compensated image reconstruction method for multi-contrast
      imaging. Shared information throughout the imaging protocol is now exploited by
      the image reconstruction in the form of an additional constraint based on image
      gradient sparsity. This constraint helps to minimize the amount of data needed
      for efficient non-rigid motion correction. T1and T2weighted images were
      reconstructed from free-breathing acquisitions in 4 healthy volunteers and in a
      phantom. The impact of multi-contrast motion correction was evaluated in a
      phantom in terms of precision and accuracy of T1and T2quantification. RESULTS: In
      the phantom, the proposed method achieved an accuracy of 97.5 % on the quantified
      parameters against 88.0 % before motion correction. In volunteers, motion
      inconsistency in T1and T2quantification were noticeably reduced within 5 min of
      free-breathing acquisition. CONCLUSION: An efficient, free-breathing, multi
      contrast imaging method has been demonstrated that does not require prior
      assumptions about contrast and that is applicable to a wide range of
      examinations.

PMID- 24659259
TI  - Impact of bifurcation stent technique on clinical outcomes in patients with a
      Medina 0,0,1 coronary bifurcation lesion: results from the COBIS (COronary
      BIfurcation Stenting) II registry.
AB  - OBJECTIVE: To compare the long-term clinical outcomes of patients treated with 1-
      versus 2-stent techniques for Medina 0,0,1 type bifurcation lesions. BACKGROUND:
      Little is known about clinical outcomes and optimal treatment strategies for
      Medina 0,0,1 type bifurcation lesions METHODS: A total of 2,897 consecutive
      patients who underwent percutaneous coronary intervention using a drug-eluting
      stent for a coronary bifurcation lesion with a side branch (SB) >=2.3 mm were
      enrolled from 18 centers in South Korea. We compared target lesion failure (TLF),
      defined as the composite of cardiac death, myocardial infarction, or target
      lesion revascularization (TLR) according to 1- or 2-stent techniques in the
      patients with a de novo Medina 0,0,1 type bifurcation lesion (n = 113, 3.9%)
      RESULTS: Fifty patients were treated with the 1-stent technique, and 63 patients
      with the 2-stent technique. During a median follow-up duration of 36.6 months,
      patients in the 1-stent technique group tended to have a higher incidence of TLR
      (3.2 versus 12.0%, P = 0.07) and TLF (4.8 versus 12.0%, P = 0.16) than those in
      the 2-stent technique group. Multivariate analysis revealed that the 1-stent
      technique was associated with a higher risk of TLR (hazard ratio [HR] 7.35; 95%
      confidence interval [CI] 1.27-42.5; P = 0.03) and TLF (HR 4.65; 95% CI 1.01-21.6;
      P = 0.05) than the 2-stent technique CONCLUSIONS: In patients with a Medina 0,0,1
      type bifurcation lesion, the 2-stent technique seems to be associated with a
      better clinical outcome compared with the 1-stent technique. These findings need
      to be confirmed in randomized controlled trials.

PMID- 24659260
TI  - Dyspnea and reversibility profile of P2Y12 antagonists: systematic review of new
      antiplatelet drugs.
AB  - BACKGROUND: Dyspnea has been consecutively reported in some trials evaluating new
      P2Y12 inhibitors. OBJECTIVE: We aimed to review and quantify the global risk of
      dyspnea of recent P2Y12 inhibitor drugs, and evaluate its association with the
      reversibility profile of P2Y12 inhibitors. METHODS: A database search (March
      2013) retrieved randomized controlled trials (RCTs) comparing new antiplatelet
      drugs (ticagrelor, prasugrel, cangrelor, elinogrel) with clopidogrel. The primary
      outcome was the incidence of dyspnea. Placebo-controlled trials were excluded.
      Meta-analysis was performed and estimates were expressed as risk ratio (RR) and
      95% confidence intervals (95% CIs). Dyspnea incidence was evaluated according to
      the reversibility profile of P2Y12 antagonists. RESULTS: We found eight RCTs
      including 41,289 patients. Prasugrel was not associated with an increased risk of
      dyspnea (RR 1.09, 95% CI 0.93-1.27), whereas ticagrelor (RR 1.95, 95% CI 1.37
      2.77), cangrelor (RR 2.42, 95% CI 1.36-4.33), and elinogrel (RR 3.25, 95% CI 1.57
      6.72) showed an increased risk of dyspnea. Reversible inhibitors significantly
      increased the risk of dyspnea compared with the irreversible inhibitor,
      prasugrel, through adjusted indirect comparison (RR 1.99, 95% CI 1.40-2.82).
      CONCLUSIONS: The reversible P2Y12 antagonists ticagrelor, cangrelor, and
      elinogrel have an increased incidence of dyspnea in increasing order when
      compared with irreversible P2Y12 inhibitors such as clopidogrel or prasugrel.

PMID- 24659261
TI  - Interventions for nausea and vomiting in early pregnancy.
AB  - BACKGROUND: Nausea, retching and vomiting are very commonly experienced by women
      in early pregnancy. There are considerable physical, social and psychological
      effects on women who experience these symptoms. This is an update of a review of
      interventions for nausea and vomiting in early pregnancy previously published in
      2010. OBJECTIVES: To assess the effectiveness and safety of all interventions for
      nausea, vomiting and retching in early pregnancy, up to 20 weeks' gestation.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register and the Cochrane Complementary Medicine Field's Trials Register (27
      April 2013). SELECTION CRITERIA: All randomised controlled trials of any
      intervention for nausea, vomiting and retching in early pregnancy. We excluded
      trials of interventions for hyperemesis gravidarum, which are covered by another
      Cochrane review. We also excluded quasi-randomised trials and trials using a
      cross-over design. DATA COLLECTION AND ANALYSIS: Four review authors, in pairs,
      reviewed the eligibility of trials and independently evaluated the risk of bias
      and extracted the data for included trials. MAIN RESULTS: Thirty-seven trials
      involving 5049 women, met the inclusion criteria. These trials covered many
      interventions, including acupressure, acustimulation, acupuncture, ginger,
      chamomile, lemon oil, mint oil, vitamin B6 and several antiemetic drugs. We
      identified no studies of dietary or other lifestyle interventions. Evidence
      regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and
      acustimulation of the P6 point was limited. Acupuncture (P6 or traditional)
      showed no significant benefit to women in pregnancy. The use of ginger products
      may be helpful to women, but the evidence of effectiveness was limited and not
      consistent, though two recent studies support ginger over placebo. There was only
      limited evidence from trials to support the use of pharmacological agents
      including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea
      and vomiting. There was little information on maternal and fetal adverse outcomes
      and on psychological, social or economic outcomes. We were unable to pool
      findings from studies for most outcomes due to heterogeneity in study
      participants, interventions, comparison groups, and outcomes measured or
      reported. The methodological quality of the included studies was mixed. AUTHORS'
      CONCLUSIONS: Given the high prevalence of nausea and vomiting in early pregnancy,
      women and health professionals need clear guidance about effective and safe
      interventions, based on systematically reviewed evidence. There is a lack of high
      quality evidence to support any particular intervention. This is not the same as
      saying that the interventions studied are ineffective, but that there is
      insufficient strong evidence for any one intervention. The difficulties in
      interpreting and pooling the results of the studies included in this review
      highlight the need for specific, consistent and clearly justified outcomes and
      approaches to measurement in research studies.

PMID- 24659262
TI  - CDKN2A unclassified variants in familial malignant melanoma: combining functional
      and computational approaches for their assessment.
AB  - CDKN2A codes for two oncosuppressors by alternative splicing of two first exons:
      p16INK4a and p14ARF. Germline mutations are found in about 40% of melanoma-prone
      families, and most of them are missense mutations mainly affecting p16INK4a. A
      growing number of p16INK4a variants of uncertain significance (VUS) are being
      identified but, unless their pathogenic role can be demonstrated, they cannot be
      used for identification of carriers at risk. Predicting the effect of these VUS
      by either a "standard" in silico approach, or functional tests alone, is rather
      difficult. Here, we report a protocol for the assessment of any p16INK4a VUS,
      which combines experimental and computational tools in an integrated approach. We
      analyzed p16INK4a VUS from melanoma patients as well as variants derived through
      permutation of conserved p16INK4a amino acids. Variants were expressed in a
      p16INK4a-null cell line (U2-OS) and tested for their ability to block
      proliferation. In parallel, these VUS underwent in silico prediction analysis and
      molecular dynamics simulations. Evaluation of in silico and functional data
      disclosed a high agreement for 15/16 missense mutations, suggesting that this
      approach could represent a pilot study for the definition of a protocol
      applicable to VUS in general, involved in other diseases, as well. 

PMID- 24659263
TI  - Association of the human astrocyte elevated gene-1 promoter variants with
      susceptibility to hepatocellular carcinoma.
AB  - Central role of astrocyte elevated gene-1 (AEG-1) in regulating diverse aspects
      of hepatocellular carcinoma (HCC) pathogenesis and association of its
      overexpression with HCC progression has been demonstrated. The positive
      regulatory regions of AEG-1 promoter contain several putative transcription
      factor binding sites critical for basal promoter activity. In this study, the aim
      was to explore the association of AEG-1 promoter variant with HCC. In this study,
      the human AEG-1 promoter including the region -538 to -42 was explored in 53 HCC
      patients and 108 healthy controls. The polymerase chain reaction-sequencing
      method was used for investigating AEG-1 promoter polymorphisms. A novel mutation
      in AEG-1 promoter in human HCC patients at a potential AP-2 binding site was
      explored. An A>C mutation was observed in -483 of AEG-1 promoter in 4 out of 53
      HCC patients but not in 108 control individuals. Sequencing data showed genetic
      variations in 11 HCC patients and 3 healthy controls. Among them, one novel SNP
      was found in activator protein-1 (AP2), a transcription factor binding site (-483
      A to C) that may be associated with the susceptibility to HCC (P = 0.012) but no
      associations were found for other observed variations. This mutation could be
      tumor-specific. AEG-1 promoter variant -483 A>C may be associated with the
      susceptibility to HCC in Iranian population. To our knowledge, this is the first
      study that has reported this association with the susceptibility to HCC.
      Therefore, further studies need to be conducted in larger sample sizes and other
      populations to validate these findings.

PMID- 24659264
TI  - MicroRNA-23a expression in paraffin-embedded specimen correlates with overall
      survival of diffuse large B-cell lymphoma.
AB  - It has been demonstrated that aberrant expression of microRNAs (miRNAs) is
      strongly associated with carcinogenesis. Recently, specific miRNAs may serve as
      potential biomarkers for the diagnosis and prognosis of various types of tumor.
      MiR-23a is known to play important role in the development of cancers and
      deregulated in various hematological malignancies. The aim of the present study
      is to explore miR-23a as potential diagnostic and/or prognostic marker of diffuse
      large B-cell lymphoma (DLBCL). We compared the expression level of miR-23a in
      DLBCL patients (n = 104) and reactive lymph nodes as controls (n = 28) from
      formalin-fixed, paraffin-embedded tissues using quantitative reverse
      transcription-polymerase chain reaction. The expression level of miR-23a was
      significantly higher in DLBCL patients than in controls (P = 0.001). No
      significant association was observed between the miR-23a expression level and
      clinical features such as age, gender, Ann Arbor stage, performance status,
      lactate dehydrogenase, extranodal sites and International Prognostic Index score
      (IPI). Kaplan-Meier analysis showed that higher expression level of miR-23a was
      significantly associated with a poor overall survival (OS) in DLBCL patients (log
      rank test, P = 0.029), and multivariable Cox regression revealed the expression
      of miR-23a (adjusted P = 0.034) and IPI (adjusted P = 0.021) was independently
      associated with OS. To our knowledge, we provide here the first evidence that miR
      23a may represent a diagnostic and prognostic marker for DLBCL. DLBCL patients
      with a high expression level of miR-23a had a shorter OS than patients with a
      lower expression level. Further investigation of the changes may be of prognostic
      significance in clinical practice.

PMID- 24659265
TI  - Stemness state regulators SALL4 and SOX2 are involved in progression and
      invasiveness of esophageal squamous cell carcinoma.
AB  - Cancer stem cells, as a subgroup of tumor cells, resemble critical properties of
      embryonic stem cells (ESCs) such as self-renewal and maintenance of stemness
      state. SALL4 and SOX2 are two main transcription factors involving in maintenance
      of pluripotency, self-renewal and cell fate decision in ESCs. In this study, we
      aimed to elucidate the expression levels of these important transcription factors
      in esophageal squamous cell carcinoma (ESCC) and to reveal their probable roles
      in maintenance and progression of the disease. The expression level of SALL4 and
      SOX2 was analyzed in fresh tumoral tissues in comparison with distant tumor-free
      tissues of 50 ESCC patients by relative comparative real-time PCR. SALL4 and SOX2
      were overexpressed in 64 and 32% of tumor samples, respectively, in significant
      correlation with each other (p = 0.028). There was a significantly inverse
      correlation between low level of SALL4 expression and metastasis of tumor cells
      into the lymph nodes (p = 0.035). Furthermore, co-overexpression of the genes was
      significantly correlated with the depth of tumor invasion (p = 0.045) and
      metastasis to the lymph nodes (p = 0.049). SALL4 and SOX2 are co-overexpressed in
      ESCC and have a significant correlation with invasion and metastasis of the
      disease. To the best of our knowledge, this is the first report of SALL4 clinical
      relevance in ESCC to date. The clinical consequences of SALL4-SOX2 association
      suggest a possible functional interaction between these factors in regulation of
      ESCC maintenance and aggressiveness and introduce these regulators of stemness
      state as potentially interesting therapeutic targets to bring new opportunities
      for onco-therapeutic modalities.

PMID- 24659266
TI  - Serum omentin level in patients with prostate cancer.
AB  - Prostate cancer (PCa) is the second leading cause of cancer-related death in
      males. Hypertriglyceridemia and obesity are known risk factors for disease
      development. Omentin is a plasma adipokine that is synthesized in visceral
      adipose tissue; its plasma concentration changes in colorectal cancer and
      conditions associated with insulin resistance. To our knowledge, the relationship
      between omentin and PCa has not been investigated previously. Therefore, we
      evaluated omentin levels in PCa patients in this matched case-control study.
      Fifty consecutive patients newly diagnosed with PCa and 30 consecutive patients
      newly diagnosed with benign prostatic hyperplasia (BPH) were assessed. Patients
      with PCa were divided into three subgroups according to the Gleason score. The
      omentin concentrations were determined using enzyme-linked immunosorbent assays.
      Blood urea nitrogen (p < 0.001), creatinine (Cr; p < 0.001), total cholesterol (p
      < 0.001), low-density lipoprotein (p < 0.001), and prostate-specific antigen
      (PSA; p = 0.03) levels were significantly higher in the PCa group than the BPH
      group. The median omentin level in BPH patients was 373 (207-792) versus 546.8
      (297.1-945.7) ng/mL in the PCa group (p < 0.001). There was a negative
      weak/moderate correlation between omentin and body mass index in the BPH group (r
      = -0.364, p = 0.048). Circulating omentin levels were elevated in patients with
      PCa. Further studies would be useful to establish the mechanism underlying this
      increase and to assess the interaction between PCa and adipose tissue.

PMID- 24659267
TI  - Assessment of tumor characteristics and factors affecting survival in patients
      with primary metastatic breast carcinoma: a Multicenter Study of the Anatolian
      Society of Medical Oncology.
AB  - Primary metastatic breast cancer (PMBC) comprises 3-10% of all BCs. PMBC is a
      heterogeneous disease. To date, little is known about the tumor characteristics,
      treatment results, and overall survival (OS) of patients with PMBC. Patients were
      considered to have PMBC if distant metastasis was evident within 3 months of the
      initial diagnosis of BC. Between September 2007 and April 2013, 466 PMBC patients
      were included in this study and analyzed retrospectively. The median age of the
      patients was 50 (18-90) years. Bone/soft tissue metastases were more frequent in
      the hormone receptor (HR)(+) human epidermal growth factor receptor (HER)2(-)
      group compared with the HR(-)HER2(-) and HR(-)HER2(+) groups (p < 0.001), whereas
      visceral organ metastasis was more frequent in the HR(-)HER2(-) and HR(-)HER2(+)
      groups (p < 0.001). The OS was affected by Eastern Cooperative Oncology Group
      performance status, tumor histology, receptor status, and the site of metastasis
      (p < 0.001, p < 0.001, p < 0.001, and p = 0.011, respectively). According to the
      first-line systemic treatment choices of the patients, the longest median OS was
      observed in the HR(+)HER2(+) group who received hormonotherapy combined with
      trastuzumab after chemotherapy (86 months, 95% CI 23.8-148.1) and the shortest
      median OS was observed in the HR(-)HER2(-) group who received chemotherapy only
      (24 months, 95% CI 17.9-30.0) (p < 0.001). Bisphosphonate therapy or radiotherapy
      had no significant effect on OS (p = 0.733, 0.603). In multivariate analysis,
      hormonotherapy, chemotherapy + trastuzumab, trastuzumab + hormonotherapy
      following chemotherapy, and surgery were the most important prognostic factors
      for OS, respectively (p < 0.001, p = 0.025, p = 0.027, p = 0.029). The general
      characteristics of the primary tumor are important for the prognosis and survival
      of patients with PMBC. Interestingly, patients who underwent primary breast tumor
      surgery, even those at the metastatic stage upon admission, had the longest
      survival.

PMID- 24659268
TI  - A pilot study of combination intraperitoneal recombinant human endostatin and
      chemotherapy for refractory malignant ascites secondary to ovarian cancer.
AB  - The management of refractory malignant ascites (MA) due to ovarian cancer (OC)
      remains a difficult clinical problem. A total of 23 eligible patients with
      refractory MA due to OC were treated with combined intraperitoneal therapy
      repeated 4 weeks, which consisted of paclitaxel 100 mg m(-2) (over 3 h) on day 1,
      5-FU 600 mg m(-2) on day 1-3 followed by recombinant human endostatin 60 mg on
      day 4. The objective response rate was 60.9 % (14/23). The median time to
      progression and overall survival was 5.8 and 12.9 months, respectively. Treatment
      related toxicities were uncommon and manageable without therapy-associated
      deaths. The mean Karnofsky performance status score was significantly improved
      from 60.0 +/- 1.89 at enrollment to 70.0 +/- 2.59 at 2 weeks after the first
      cycle of therapy (P = 0.000). Moreover, the mean score of overall ascites
      associated symptoms was also increased significantly from 5.1 +/- 0.32 to 4.0 +/-
      0.20 (P = 0.002). There were remarkable improvements in 7 out of 9 individual
      ascites-associated symptoms including well being, anxiety, abdominal distention,
      vomiting, anorexia, fatigue, and dyspnea as well (all P < 0.05). These results
      suggest that combination intraperitoneal recombinant human endostatin and
      chemotherapy is effective and safe in patients with refractory MA secondary to OC
      and significantly improves patients' quality of life with encouraging survival,
      which might highlight more effective treatment for this challenging disease and
      merits further investigation.

PMID- 24659271
TI  - Self-assembled silver nanoparticles in a bow-tie antenna configuration.
AB  - The self-assembly of silver nanoparticles into a bow-tie antenna configuration is
      achieved with the DNA origami method. Instead of complicated particle geometries,
      spherical silver nanoparticles are used. Formation of the structures in high
      yields is verified with transmission electron microscopy and agarose gel
      electrophoresis. According to finite-difference time-domain simulations, the
      antenna configuration could be used as a DNA sensor.

PMID- 24659273
TI  - The in vivo radiosensitizing effect of gold nanoparticles based MRI contrast
      agents.
AB  - Owing to the high atomic number (Z) of gold element, the gold nanoparticles
      appear as very promising radiosensitizing agents. This character can be exploited
      for improving the selectivity of radiotherapy. However, such an improvement is
      possible only if irradiation is performed when the gold content is high in the
      tumor and low in the surrounding healthy tissue. As a result, the beneficial
      action of irradiation (the eradication of the tumor) should occur while the
      deleterious side effects of radiotherapy should be limited by sparing the healthy
      tissue. The location of the radiosensitizers is therefore required to initiate
      the radiotherapy. Designing gold nanoparticles for monitoring their distribution
      by magnetic resonance imaging (MRI) is an asset due to the high resolution of MRI
      which permits the accurate location of particles and therefore the determination
      of the optimal time for the irradiation. We recently demonstrated that ultrasmall
      gold nanoparticles coated by gadolinium chelates (Au@DTDTPA-Gd) can be followed
      up by MRI after intravenous injection. Herein, Au@DTDTPA and Au@DTDTPA-Gd were
      prepared in order to evaluate their potential for radiosensitization. Comet
      assays and in vivo experiments suggest that these particles appear well suited
      for improving the selectivity of the radiotherapy. The dose which is used for
      inducing similar levels of DNA alteration is divided by two when cells are
      incubated with the gold nanoparticles prior to the irradiation. Moreover, the
      increase in the lifespan of tumor bearing rats is more important when the
      irradiation is performed after the injection of the gold nanoparticles. In the
      case of treatment of rats with a brain tumor (9L gliosarcoma, a radio-resistant
      tumor in a radiosensitive organ), the delay between the intravenous injection and
      the irradiation was determined by MRI.

PMID- 24659274
TI  - Identifying Male Sexual Offender Subtypes Using Cluster Analysis and the Static
      2002R.
AB  - This study examines whether clinically meaningful subgroups could be identified
      within a large, undifferentiated group of convicted adult male sex offenders. Of
      eight cluster analyses, a reliable three-cluster solution emerged based on the
      subscores of the Static-2002R with 345 sex offenders. To establish the validity
      of the emergent clusters, the three groups of offenders were compared on four
      domains: criminal history, psychosexual development, sexual attitudes and
      interests, and recidivism. The findings revealed meaningful differences among the
      group, and the implications of subgroup membership is discussed in terms of risk,
      treatment, and supervision. 

PMID- 24659275
TI  - The role of membrane cholesterol in effects of beta2 adrenoreceptors activation
      of the mouse atrium.

PMID- 24659276
TI  - The developing brain as an endocrine source of norepinephrine in the blood.

PMID- 24659277
TI  - Relationship between the changes in peripheral thresholds of nociception and
      activity of the adenylyl cyclase system in the skeletal muscles of rats with
      streptozotocin-induced diabetes.

PMID- 24659278
TI  - The chronic inhibition of dopamine synthesis in the brain of neonatal rats as an
      evidence of its endocrine function in ontogeny.

PMID- 24659279
TI  - The effect of the natural dipeptide carnosine on learning of rats under the
      conditions of negative reinforcement.

PMID- 24659280
TI  - Immunization with a non-replicating antigen leads to changes in song
      characteristics and the level of corticosterone in passerine birds.

PMID- 24659281
TI  - Variation of the epiphytic lichen diversity in a gradient of atmospheric
      pollution: do taxonomic, genetic, and functional distances between species add
      any information?

PMID- 24659283
TI  - Chromosomal polymorphism in the peripheral population of the root vole Mirotus
      oeconomus (Rodentia, Arvicolinae) of the Valdai National Park.

PMID- 24659282
TI  - Phytoplankton photoadaptation to photoinhibition in the tropical part of the
      atlantic ocean.

PMID- 24659284
TI  - "New" benthic community dominated by Oweniidae (Polychaeta, Oweniidae) at the
      Murman coast: structure and causes of appearance.

PMID- 24659285
TI  - Spreading of deterrency as a means of chemical defense among aquatic organisms
      inhabiting the coral reefs of Vietnam.

PMID- 24659286
TI  - Correlations in the rhythmic organization of singing in the great reed warbler
      (Acrocephalus andinaceus, Sylviidae, Aves).

PMID- 24659287
TI  - Role of tactile sense and other sensory systems in control of feeding behavior in
      gourami of the genus Trichopodus.

PMID- 24659288
TI  - Ciliary cells in the epidermis, gut, and gonads of sea spiders (Pycnogonida).

PMID- 24659289
TI  - Amicable and aggressive behavior as factors of formation of species-specific
      family-group relations in rodents.

PMID- 24659290
TI  - Differential sex-dependent postimplantation embryo mortality of the water vole
      (Arvicola amphibius).

PMID- 24659291
TI  - Symbiotic mutants of pea (Pisum sativum L.), an important genetic source for
      selection for increased nitrogen fixation.

PMID- 24659292
TI  - Audiogenic seizure proneness after methyl-enriched diet in ontogeny.

PMID- 24659294
TI  - Effect of rotation and immobilization stress on IL-1beta, IL-2, IL-4, and IFN
      gamma production by splenocytes under opiate receptor blockade in vivo.

PMID- 24659293
TI  - Hormonal regulation of thymic-stage differentiation of IL-17-producing and T
      regulatory lymphocytes.

PMID- 24659295
TI  - Human leukemia differentiation factor (HLDF) controls the cytokine-producing
      function of blood cells in gastric adenocarcinomas.

PMID- 24659296
TI  - In situ electron microscopic detection of proteasomes in apoptotic U937 cells.

PMID- 24659298
TI  - Reply to: The many faces of TUBB4A mutations.

PMID- 24659297
TI  - Dysregulated expression of lipid storage and membrane dynamics factors in Tia1
      knockout mouse nervous tissue.
AB  - During cell stress, the transcription and translation of immediate early genes
      are prioritized, while most other messenger RNAs (mRNAs) are stored away in
      stress granules or degraded in processing bodies (P-bodies). TIA-1 is an mRNA
      binding protein that needs to translocate from the nucleus to seed the formation
      of stress granules in the cytoplasm. Because other stress granule components such
      as TDP-43, FUS, ATXN2,SMN, MAPT, HNRNPA2B1, and HNRNPA1 are crucial for the motor
      neuron diseases amyotrophic lateral sclerosis (ALS)/spinal muscular atrophy (SMA)
      and for the frontotemporal dementia(FTD), here we studied mouse nervous tissue to
      identify mRNAs with selective dependence on Tia1 deletion. Transcriptome
      profiling with oligonucleotide microarrays in comparison of spinal cord and
      cerebellum, together with independent validation in quantitative reverse
      transcriptase PCR and immunoblots demonstrated several strong and consistent
      dysregulations. In agreement with previously reported TIA1 knock down effects,
      cell cycle and apoptosis regulators were affected markedly with expression
      changes up to +2-fold, exhibiting increased levels for Cdkn1a, Ccnf, and Tprkb
      vs.decreased levels for Bid and Inca1 transcripts. Novel and surprisingly strong
      expression alterations were detected for fat storage and membrane trafficking
      factors, with prominent +3-fold upregulations of Plin4, Wdfy1, Tbc1d24, and
      Pnpla2 vs. a -2.4-fold downregulation of Cntn4 transcript, encoding an axonal
      membrane adhesion factor with established haploinsufficiency.In comparison,
      subtle effects on the RNA processing machinery included up to 1.2-fold
      upregulations of Dcp1b and Tial1. The effect on lipid dynamics factors is
      noteworthy, since also the gene deletion of Tardbp (encoding TDP-43) and Atxn2
      led to fat metabolism phenotypes in mouse. In conclusion, genetic ablation of the
      stress granule nucleator TIA-1 has a novel major effect on mRNAs encoding lipid
      homeostasis factors in the brain, similar to the fasting effect.

PMID- 24659299
TI  - Relationship of youth involvement in diabetes-related decisions to treatment
      adherence.
AB  - The aim of this study was to examine the relationship of youth's involvement in
      diabetes-related decisions to adherence. Children and adolescents (8-19 years)
      and their parents (N = 89) completed the Decision Making Involvement Scale and
      the Self Care Inventory, a self-report measure of adherence. After controlling
      for youth age, the degree to which youth expressed an opinion and information to
      parents was associated with better parent- and youth-reported adherence. The
      degree to which parents expressed an opinion and information to youth was
      associated with worse parent-reported adherence. Joint decision-making behaviors
      (e.g., negotiation; provision of options) also were associated with better youth
      reported adherence. Encouraging youth to express opinions and share illness
      related information with parents during illness management discussions may
      improve adherence. Additional research is needed to identify mechanisms of effect
      and determine associations between decision making involvement and health
      behaviors and outcomes over time.

PMID- 24659300
TI  - Health-related hindrance of personal goals of adolescents with cancer: The role
      of the interaction of race/ethnicity and income.
AB  - This study examined the interaction of race/ethnicity and income to health
      related hindrance (HRH) of personal goals of adolescents with cancer. Adolescents
      (N = 94) receiving treatment for cancer completed a measure of HRH, (including
      identification of personal goals, rating the impact of health on goal pursuit,
      and ratings of goal appraisals). The interaction of race/ethnicity and income on
      HRH was examined. Goal content and appraisal were compared by race/ethnic groups.
      The interaction between race/ethnicity and income was significant in predicting
      HRH, with HRH increasing for minority adolescents as income increases and HRH
      decreasing for white adolescents as income increases. Higher income minority
      adolescents reported the most goals. Low income minorities reported the least
      difficult goals. Goal content did not differ between groups. Sociodemographic
      factors contribute to HRH in adolescents with cancer. Structural and psychosocial
      support during treatment to maintain goal pursuit may improve psychosocial
      outcomes.

PMID- 24659301
TI  - Spatial predictors of bovine tuberculosis infection and Brucella  spp. exposure
      in pastoralist and agropastoralist livestock herds  in the Ruaha ecosystem of
      Tanzania.
AB  - While many studies investigate animal-related risk factors for disease, few have
      considered environmental or spatial risk factors in the dynamics of bovine
      tuberculosis (bTB) and brucellosis. In the Ruaha ecosystem of Tanzania, we
      investigated the role of household location as a predictor for infection with
      Mycobacterium bovis and exposure to Brucella in pastoralist and agropastoralist
      cattle herds in a typical African wildlife-livestock-human interface. ArcGIS was
      utilized to calculate Euclidian distances between households and the nearest
      river, village center, protected area, and other infected households, followed by
      multivariate logistic regression to assess the association between risk factors
      and herd-level bTB and Brucella outcomes. Global and local spatial clustering of
      bTB-infected and Brucella-exposed herds was explored using the Cuzick-Edward's
      test and SaTScan spatial scan statistics. Households located farther from rivers
      and closer to village centers and herds belonging to agropastoralists were more
      likely to have bTB-positive cattle. Risk of Brucella exposure increased with
      proximity to protected areas. One spatial cluster of households with Brucella
      spp. seropositive cattle was identified. Spatial factors may be useful for
      assessing disease risk and for formulating intervention and control strategies
      for households that manage cattle in ecosystems characterized by seasonally
      limited resources and intense wildlife-livestock interfaces.

PMID- 24659302
TI  - Effect of different management systems on rutting behavior  and behavioral
      repertoire of housed Maghrebi male camels  (Camelus dromedarius).
AB  - Camel management has been changing in recent years from an extensive to a semi
      intensive or intensive system, particularly for breeding bulls and dairy
      dromedary camels. Captivity may affect animal welfare, and low libido is the
      major complaint for housed breeding bulls. Since welfare status could also affect
      reproductive performance, the aim of this study was to evaluate different
      management practices on behavior, particularly on sexual behavior, and to
      identify some behavioral needs of male dromedary camels reared for semen
      collection. The effects of the following management systems on their behavior
      were compared: (i) traditional: housing in a single stall for 24 h (H24), (ii)
      housing in a single stall for 23 h with 1 h free in the paddock (H23), and (iii)
      housing in a single stall for 22 h and 30 min with 1 h paddock time and 30 min
      exposure to a female camel herd (ExF). During the trial, blood cortisol
      concentrations were assessed and camels were filmed daily for 30 min in the
      mornings and during a female passage in the evenings. Videos were analyzed in
      order to fill out a focal sampling ethogram and to score sexual behavior. As a
      result, there were no differences between the H24 and H23 systems, whereas ExF
      had a significant positive impact on their sexual behavior score and behavioral
      repertoire, further reducing cortisol levels. Overall, it seems that male
      dromedary camel welfare status improves when their behavioral needs for social
      interaction and movement are satisfied.

PMID- 24659303
TI  - High-performance quantum-dot solids via elemental sulfur synthesis.
AB  - An elemental-sulfur-based synthesis is reported, which, combined with processing
      to improve the size dispersion and passivation, results in a low-cost high
      quality platform for small-bandgap PbS-CQD-based devices. Size-selective
      precipitation and cadmium chloride passivation are used to improve the power
      conversion efficiency of 1 eV bandgap CQD photovoltaic devices dramatically,
      which leads to record power conversion efficiency for a 1 eV PbS CQD solar cell
      of 5.4%. 

PMID- 24659304
TI  - Open Tibial Pilon Fracture With Wound Botulism Exacerbated by Aminoglycoside
      Antibiotic Beads: Case Report.

PMID- 24659305
TI  - Ulnocarpal impaction syndrome: treatment with a transverse ulnar shortening
      osteotomy from an ulnodorsal approach.
AB  - INTRODUCTION: Ulnocarpal impaction syndrome is a common cause of chronic ulnar
      sided wrist pain. The distal ulnar shortening osteotomy addresses the often
      present positive ulnar variance and therefore relieves the excessive load on the
      ulnocarpal joint. In the present study, the results of a technique that uses an
      ulnodorsal approach with a compression device and a transverse osteotomy are
      presented and compared to other techniques. MATERIALS AND METHODS: This
      retrospective study includes 92 wrists with an ulnocarpal impaction syndrome,
      which were treated with an ulnar shortening osteotomy. The mean duration of
      postoperative follow-up was 50 months. RESULTS: The mean ulnar variance was 2.17
      +/- 1.56 mm preoperatively and after the ulnar shortening osteotomy -1.36 +/-
      1.67 mm (p < 0.05). Radiological consolidation of the osteotomy could be shown in
      91 wrists 6 months postoperatively. Patients rated the preoperative pain level at
      a VAS 7.9 +/- 1.7 which decreased to a of VAS 2.4 +/- 2.5 (p < 0.05). 19 patients
      complained of mechanical irritation. There was no neurological irritation.
      CONCLUSION: It could be shown that the distal ulnar shortening osteotomy by a
      transverse osteotomy using a compression device and an ulnodorsal approach has a
      low complication rate. It is comparable to the oblique osteotomy in effectiveness
      and safety.

PMID- 24659306
TI  - Association mapping for five agronomic traits in the common bean (Phaseolus
      vulgaris L.).
AB  - BACKGROUND: The common bean is the most important grain legume and a major source
      of protein in many developing countries. We analysed the following traits: pod
      fibre (PF), seeds per pod (SPP), plant type (PT), growth habit (GH), and days to
      flowering (DF) for a set of diverse common bean accessions and determined whether
      such traits were associated with amplified fragment length polymorphism (AFLP),
      simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers.
      RESULTS: In this study, 66 common bean genotypes were used and genotyped with 233
      AFLP, 105 SNP and 80 SSR markers. The association analysis between markers and
      five traits was performed using a General Linear Model (GLM) in Trait Analysis by
      aSSociation, Evolution and Linkage (TASSEL). The population structure was
      determined using the STRUCTURE software, and seven groups (K = 7) were identified
      among genotypes. The associations for such traits were identified and quantified;
      62 markers were associated with the five traits. CONCLUSION: This study
      demonstrated that association mapping using a reasonable number of markers,
      distributed across the genome and with the appropriate number of individuals
      harboured to detect DNA markers linked to the traits of PF, SPP, PT, GH and DF in
      common bean.

PMID- 24659307
TI  - Are videolaryngoscopes useful for nasotracheal intubation?

PMID- 24659309
TI  - A cardiac diagnosis by contrast echocardiography.

PMID- 24659310
TI  - New proposed guidelines for early identification of successful myeloid and
      erythroid engraftment in hematopoietic stem cell transplantation.
AB  - BACKGROUND: After hematopoietic stem cell transplantation (HSCT), early detection
      of engraftment would be of critical value for clinicians. The aim of this study
      was to identify faster parameters for engraftment. METHODS: We evaluated blood
      cell parameters including complete blood count (CBC), differential counts, and
      various reticulocyte parameters in 115 patients who received HSCT (allogeneic, n
      = 93; autologous, n = 22) in the purpose of identifying possible improved
      laboratory guidelines for engraftment prediction. RESULTS AND CONCLUSION: Days to
      white blood cell (WBC) count over 100 cells/MUl with more than two-fold increase
      from nadir after transplantation (proposed new WBC guideline) preceded absolute
      neutrophil count (ANC) >500 cells/MUl by 1.7 days. Among erythroid parameters,
      the earliest marker for erythroid engraftment was high light scattering
      reticulocytes (HLR) >0.1 (proposed new red blood cell guideline), which preceded
      reticulocyte counts (RET) >1% and immature reticulocyte fraction >0.5 by 3.9 and
      1.6 days, respectively. Among the clinical parameters compared, those with
      statistically significant influence on myeloid engraftment were donor type (P =
      0.009) and conditioning intensity (P = 0.009). As for erythroid recovery, ABO
      incompatibility was the only significant factor. In conclusion, the new
      guidelines may ensure engraftment several days earlier than the conventional
      parameters, which may help clinicians for decision-making on rescue therapy
      earlier.

PMID- 24659312
TI  - Evaluation of echogenicity of the heart in Kawasaki disease.
AB  - Pathologic studies of the heart in patients with Kawasaki disease (KD) revealed
      vasculitis, valvulitis, myocarditis, and pericarditis. However, there have been
      no studies on the quantitative determination of multi-site echogenicity of the
      heart in KD patients. It is also undetermined whether the degree of echogenicity
      of each site of the heart in patients with KD might be related to the response to
      intravenous immunoglobulin (IVIG) treatment. In 81 KD patients and 30 control
      subjects, we prospectively analyzed echogenicity of the heart. Echogenicity was
      measured in four sites: coronary artery wall (CAW), mitral valve (MV), papillary
      muscle (PM), and ascending aortic wall (AAo wall) by the calibrated integrated
      backscatters (cIBs). The cIB values of all measurement sites at acute phase in KD
      patients were significantly higher than those in control subjects (KD patients vs
      control subjects; CAW, 19.8 +/- 6.2 dB vs 14.5 +/- 2.0 dB, p < 0.05; MV, 23.3 +/-
      5.3 dB vs 16.0 +/- 3.3 dB, p < 0.05; PM, 22.4 +/- 5.1 dB vs 12.7 +/- 1.9 dB, p <
      0.05; AAo wall, 25.3 +/- 5.6 dB vs 18.3 +/- 3.4 dB, p < 0.05). The cIB values of
      CAW at the acute phase in IVIG nonresponders were significantly higher than those
      in responders. Conclusion: Echogenicity of the heart in KD patients at the acute
      phase increased not only in the coronary artery wall but also in other parts of
      the heart. Echogenicity of CAW might be helpful in determining the
      unresponsiveness of IVIG treatment.

PMID- 24659311
TI  - An assessment of iron overload in children treated for cancer  and nonmalignant
      hematologic disorders.
AB  - Our goal was to assess the natural fate of iron overload (IO) following
      transfusions of packed red blood cells (PRBCs) in children treated for cancer and
      nonmalignant disorders according to the intensity level of their treatment. Sixty
      six children were followed up from February 2010 to March 2013. The transfusion
      burden was compared between three treatment intensity groups assigned according
      to the Intensity of Treatment Rating Scale 3.0 (ITR-3). IO was assessed by serial
      measurements of serum ferritin (SF) (n= 66) and quantification of tissue iron by
      magnetic resonance imaging (MRI) (n=12). Of the children studied, 36 % (24/66)
      received moderately intensive treatment (level 2), 21 % (14/ 66) received very
      intensive treatment (level 3), and 42 % (28/ 66) received the most intensive
      treatment (level 4). The number of PRBC (p=0.016), the total transfused volume
      (p= 0.026), and transfused volume adjusted to body weight (p= 0.004) were
      significantly higher in the level 4 group. By the median follow-up time of 35.5
      months (range 8-133), 21- 29 % of patients (including level 2 and level 3
      children) had SF >1,000 MUg/l 1 year after cessation of transfusions. The slowest
      decrease of SF was observed in the level 4 group. Initial MRI examination
      demonstrated either mild or moderate IO in the liver and spleen. Repetitive MRI
      showed significant improvement in relaxation time between the initial and follow
      up MRI performances in the liver (5.9 vs. 8.6 ms, p= 0.03) and the spleen (4.3
      vs. 8.8 ms, p=0.03). CONCLUSION: IO diminished over time, but in the level 4
      patients, it was detectable for years after cessation of transfusions.

PMID- 24659313
TI  - Voiding urosonography with second-generation ultrasound  contrast versus
      micturating cystourethrography  in the diagnosis of vesicoureteric reflux.
AB  - Vesicoureteric reflux has been associated with paediatric urinary tract
      infection. Fluoroscopic micturating cystourethrography (MCU) has been the gold
      standard of diagnostic test for decades; however, it has been criticized owing to
      its lower detection rate and radiation dose to children. Therefore, new radiation
      free reflux imaging modalities have been developed, in which ultrasound-based
      contrast-enhanced voiding urosonography (ceVUS) is a good example. However,
      ultrasonography has been considered as an operator-dependent examination.
      Therefore, our study aimed to examine the inter-observer agreement of this
      sonographic technique, which has not been evaluated before. Moreover, the second
      generation ultrasound contrast SonoVue has been recently marketed, and the data
      on its efficacy on intravesical use in ceVUS is relatively scarce. Thus, we also
      aimed to investigate the diagnostic performance and safety profile of SonoVue
      enhanced VUS in the diagnosis of vesicoureteric reflux. Our prospective
      comparative study compared the diagnostic performance of ceVUS with MCU in young
      children presenting with first episode of urinary tract infection. We performed
      sequential ceVUS and MCU examinations in 31 patients (62 pelvi-ureter units).
      Perfect inter-observer agreement (Cohen's kappa statistics = 1.0, p < 0.001) was
      achieved in ceVUS, suggesting its good reliability in reflux detection and
      grading. Using MCU as reference, ceVUS had 100 % sensitivity and 84 % specificity
      and carried higher reflux detection rate than MCU (p < 0.001). There was no
      complication encountered. Conclusion: Voiding urosonography is a reliable,
      sensitive, safe and radiation-free modality in the investigation of
      vesicoureteric reflux in children. It should be incorporated in the diagnostic
      algorithm in paediatric urinary tract infection.

PMID- 24659314
TI  - Single-port video-assisted thoracoscopic right upper lobectomy using a flexible
      videoscope.
AB  - Single-port video-assisted thoracoscopic surgery (VATS) has recently been
      proposed as an innovative minimally invasive alternative to the standard three
      port VATS for lobectomies, most of which are performed using a conventional rigid
      thoracoscope. Here, we report a single-port VATS approach for right upper
      lobectomy and systematic lymph node dissection using a flexible endoscope. A 61
      year-old male smoker presented with a pulmonary nodule. A single-port VATS
      procedure was performed through a 4-cm intercostal incision using a flexible
      laparo-thoraco videoscope. Right upper lobectomy and systematic lymph node
      dissection were performed. The total operating time was 106 in. The procedure was
      successful and the recovery uneventful. The patient's chest tube was removed on
      the third day, and he was discharged home on the fourth. The use of a flexible
      videoscope facilitated the single-port VATS procedure by avoiding interference
      between the videoscope and other operating instruments and providing ample space
      for the surgeon.

PMID- 24659315
TI  - Internal mammary artery pedicle: a solution for prophylactic flap coverage in
      high-risk trans-sternal thoracic surgery.
AB  - Prophylactic use of vascularized flaps to buttress and reinforce bronchial or
      oesophageal closure is nowadays the preferred approach in high-risk cases,
      especially for extended resections with tracheobronchial reconstructions or after
      neoadjuvant chemoradiotherapy. However, the majority of these options and
      techniques are described for an approach through a thoracotomy. Due to anatomical
      restrictions, these options are less suitable when a trans-sternal approach is
      used. We emphasize the use of an internal mammary artery pedicle as prophylactic
      flap coverage in 3 high-risk cases, all operated on through a median sternotomy. 

PMID- 24659316
TI  - Extracorporeal membrane oxygenation as a bridge to lung transplantation: a long
      term study.
AB  - OBJECTIVES: We investigated early outcomes in patients with end-stage pulmonary
      disease bridged with extracorporeal membrane oxygenation (ECMO) with the
      intention to perform lung transplantation (LTx). METHODS: ECMO was used as a
      bridge to LTx in 20 patients between 2005 and 2013. Most patients suffered from
      rapid progress of disease and most failed to stabilize on mechanical ventilation.
      Sixteen patients (10 males, median age 42 years, range 25-59) underwent LTx after
      ECMO support for a median of 9 (range 1-229) days. Most patients were not on the
      waiting list while receiving ECMO, but after being assessed were on the waiting
      list for a median of 6 (range 1-72) days before LTx or death occurred. Median
      follow-up at 535 (range 36-3074) days was 100% complete, 9 patients have been
      followed for >1 year and 4 patients have been bridged during 2013. RESULTS: Four
      patients died on ECMO waiting for a donor and as intention-to-treat, the success
      for bridging was 80% (16/20) and 1-year survival was 62% (10/16, not including 4
      with <1-year follow-up). For those who underwent LTx, 3 patients died in-hospital
      after LTx on Days 0, 16 and 82, respectively, and currently, 11/16 (69%) are
      alive and 1-year survival for transplanted patients was 9/12 (75%). Median ICU
      stay before and after LTx was 9 (range 2-229) days and 20 (range 0-53) days,
      respectively. At follow-up, lung function was evaluated, and mean forced
      expiratory volume at 1 s and forced vital capacity were 56+/-22% of predicted and
      74+/-24% of predicted, respectively. CONCLUSIONS: ECMO used as a bridge to LTx
      results in acceptable survival in selected patients with end-stage pulmonary
      disease.

PMID- 24659317
TI  - National review of use of extracorporeal membrane oxygenation as respiratory
      support in thoracic surgery excluding lung transplantation.
AB  - OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) for respiratory support is
      increasingly used in intensive care units (ICU), but rarely during thoracic
      surgical procedures outside the transplantation setting. ECMO can be an
      alternative to cardiopulmonary bypass for major trachea-bronchial surgery and
      single-lung procedures without in-field ventilation. Our aim was to evaluate the
      intraoperative use of ECMO as respiratory support in thoracic surgery: benefits,
      indications and complications. METHODS: This was a multicentre retrospective
      study (questionnaire) of use of ECMO as respiratory support during the thoracic
      surgical procedure. Lung transplantation and lung resection for tumour invading
      the great vessels and/or the left atrium were excluded, because they concern
      respiratory and circulatory support. RESULTS: From March 2009 to September 2012,
      17 of the 34 centres in France applied ECMO within veno-venous (VV) (n=20) or
      veno-arterial (VA) (n=16) indications in 36 patients. Ten VA ECMO were performed
      with peripheral cannulation and 6 with central cannulation; all VV ECMO were
      achieved through peripheral cannulation. Group 1 (total respiratory support) was
      composed of 28 patients without mechanical ventilation, involving 23 tracheo
      bronchial and 5 single-lung procedures. Group 2 (partial respiratory support) was
      made up of 5 patients with respiratory insufficiency. Group 3 was made up of 3
      patients who underwent thoracic surgery in a setting of acute respiratory
      distress syndrome (ARDS) with preoperative ECMO. Mortality at 30 days in Groups
      1, 2 and 3 was 7, 40 and 67%, respectively (P<0.05). In Group 1, ECMO was weaned
      intraoperatively or within 24 h in 75% of patients. In Group 2, ECMO was weaned
      in ICU over several days. In Group 1, 2 patients with VA support were converted
      to VV support for chronic respiratory indications. Bleeding was the major
      complication with 17% of patients requiring return to theatre for haemostasis.
      There were two cannulation-related complications (6%). CONCLUSIONS: VV or VA ECMO
      is a satisfactory alternative to in-field ventilation in complex tracheo
      bronchial surgery or in single-lung surgery. ECMO should be considered and used
      in precarious postoperative respiratory conditions. Full respiratory support can
      be achieved with VV ECMO. Indications for and results of ECMO during surgery in
      patients with ARDS warrant further careful investigation.

PMID- 24659318
TI  - A new perspective of shape recognition to discover the phase transition of finite
      size clusters.
AB  - An ultrafast shape-recognition technique was used to analyze the phase transition
      of finite-size clusters, which, according to our research, has not yet been
      accomplished. The shape of clusters is the unique property that distinguishes
      clusters from bulk systems and is comprehensive and natural for structural
      analysis. In this study, an isothermal molecular dynamics simulation was
      performed to generate a structural database for shape recognition of Ag-Cu
      metallic clusters using empirical many-body potential. The probability contour of
      the shape similarity exhibits the characteristics of both the specific heat and
      Lindemann index (bond-length fluctuation) of clusters. Moreover, our
      implementation of the substructure to the probability of shapes provides a
      detailed observation of the atom/shell-resolved analysis, and the behaviors of
      the clusters were reconstructed based on the statistical information. The method
      is efficient, flexible, and applicable in any type of finite-size system,
      including polymers and nanostructures.

PMID- 24659320
TI  - Pharmacotherapies for sleep disturbances in Alzheimer's disease.
AB  - BACKGROUND: Sleep disturbances, including reduced nocturnal sleep time, sleep
      fragmentation, nocturnal wandering and daytime sleepiness are common clinical
      problems in dementia due to Alzheimer's disease (AD), and are associated with
      significant caregiver distress, increased healthcare costs and
      institutionalisation. Drug treatment is often sought to alleviate these problems,
      but there is significant uncertainty about the efficacy and adverse effects of
      the various hypnotic drugs in this vulnerable population. OBJECTIVES: To assess
      the effects, including common adverse effects, of any drug treatment versus
      placebo for sleep disorders in people with Alzheimer's disease through
      identification and analysis of all relevant randomized controlled trials (RCTs).
      SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane
      Dementia and Cognitive Improvement Group's Specialized Register, on 31 March 2013
      using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence,
      "rest-activity", sundowning. SELECTION CRITERIA: We included RCTs that compared a
      drug with placebo and that had the primary aim of improving sleep in people with
      Alzheimer's disease who had an identified sleep disturbance at baseline. Trials
      could also include non-pharmacological interventions as long as both drug and
      placebo groups had the same exposure to them. DATA COLLECTION AND ANALYSIS: Two
      authors working independently extracted data on study design, risk of bias and
      results from the included study reports. Additional information was obtained from
      study authors where necessary. We used the mean difference as the measure of
      treatment effect and, where possible, synthesized results using a fixed-effect
      model. MAIN RESULTS: We found RCTs eligible for inclusion for three drugs:
      melatonin (209 participants, three studies, but only two yielded data suitable
      for meta-analysis), trazodone (30 participants, one study) and ramelteon (74
      participants, one study, no peer-reviewed publication, very limited information
      available).The melatonin and trazodone studies were of people with moderate-to
      severe AD; the ramelteon study was of people with mild-to-moderate AD. In all
      studies participants had a variety of common sleep problems. All primary sleep
      outcomes were measured using actigraphy. In one study of melatonin, drug
      treatment was combined with morning bright light therapy. Only two studies made a
      systematic assessment of adverse effects. Overall, the published studies were at
      low risk of bias, although there were areas of incomplete reporting and some
      problems with participant attrition, related largely to poor tolerance of
      actigraphy and technical difficulties. The risk of bias in the ramelteon study
      was unclear due to incomplete reporting.We found no evidence that melatonin,
      either immediate- or slow-release, improved any major sleep outcome in patients
      with AD. We were able to synthesize data for two sleep outcomes: total nocturnal
      sleep time (MD 10.68 minutes, 95% CI -16.22 to 37.59, two studies), and the ratio
      of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03, two
      studies). Other outcomes were reported in single studies. We found no difference
      between intervention and control groups for sleep efficiency, time awake after
      sleep onset or number of night-time awakenings, nor in cognition or performance
      of activities of daily living (ADLs). No serious adverse effects of melatonin
      were reported in the included studies.Trazodone 50 mg administered at night for
      two weeks significantly improved total nocturnal sleep time (MD 42.46 minutes,
      95% CI 0.9 to 84.0, one study) and sleep efficiency (MD 8.53, 95% CI 1.9 to 15.1,
      one study), but there was no clear evidence of any effect on the amount of time
      spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6, one study) or the
      number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8, one study). No
      effect was seen on daytime sleep, nor on cognition or ADLs. No serious adverse
      effects were reported.Results from a phase 2 trial investigating ramelteon 8 mg
      administered at night were available in summary form in a sponsor's synopsis.
      Ramelteon had no effect on total nocturnal sleep time at one week (primary
      outcome) or eight weeks (end of treatment). The synopsis reported few significant
      differences from placebo for any sleep, behavioural or cognitive outcomes; none
      were likely to be of clinical significance. There were no serious adverse effects
      of ramelteon. AUTHORS' CONCLUSIONS: We discovered a distinct lack of evidence to
      help guide drug treatment of sleep problems in AD. In particular, we found no
      RCTs of many drugs that are widely prescribed for sleep problems in AD, including
      the benzodiazepine and non-benzodiazepine hypnotics, although there is
      considerable uncertainty about the balance of benefits and risks associated with
      these common treatments. From the studies we identified for this review, we found
      no evidence that melatonin is beneficial to AD patients with moderate to severe
      dementia and sleep problems. There is some evidence to support the use of a low
      dose (50 mg) of trazodone, although a larger trial is needed to allow a more
      definitive conclusion to be reached on the balance of risks and benefits. There
      was no evidence of any effect of ramelteon on sleep in patients with mild to
      moderate dementia due to AD. This is an area with a high need for pragmatic
      trials, particularly of those drugs that are in common clinical use for sleep
      problems in AD. Systematic assessment of adverse effects is essential.

PMID- 24659319
TI  - The use of molecular genetics to refine prognosis in acute myeloid leukemia.
AB  - The discovery and application of advanced molecular techniques, such as gene and
      microRNA expression profiling, whole genome and exome sequencing, proteomic
      analysis and methylation assays, have allowed for the identification of recurrent
      molecular abnormalities in acute myeloid leukemia (AML) that have revolutionized
      our understanding of the genetic landscape of the disease. These modalities have
      emerged as valuable tools that permit a more comprehensive and detailed molecular
      characterization of AML. Many of these molecular abnormalities have been shown to
      predict prognosis, particularly within the context of cytogenetically normal AML.
      This review will discuss the major techniques and platforms that have been used
      to identify novel recurrent gene mutations in AML and briefly describe how these
      discoveries have impacted on outcome prediction.

PMID- 24659321
TI  - Cancer communications: from hyoid bones to nanochips.

PMID- 24659322
TI  - Contribution of retinal ganglion cells to the mouse electroretinogram.
AB  - PURPOSE: To quantify the direct contribution of retinal ganglion cells (RGCs) on
      individual components of the mouse electroretinogram (ERG). METHODS: Dark- and
      light-adapted ERGs from mice 8 to 12 weeks after optic nerve transection (ONTx,
      n=14) were analyzed through stimulus response curves for a- and b-waves,
      oscillatory potentials (OPs), positive and negative scotopic threshold response
      (p/n STR), and the photopic negative response (PhNR) and compared with unoperated
      and sham-operated controls, as well as to eyes treated with 6-cyano-7
      nitroquinoxaline-2,3-dion (CNQX). RESULTS: We confirmed in mice that CNQX
      intravitreal injection reduced the scotopic a-wave amplitude at high flash
      strength, confirming a post-receptoral contribution to the a-wave. We found that
      ONTx, which is more specific to RGCs, did not affect the a-wave amplitude and
      implicit time in either photopic or scotopic conditions while the b-wave was
      reduced. Both the pSTR and nSTR components were reduced in amplitude, with the
      balance between the two components resulting in a shortening of the nSTR peak
      implicit time. On the other hand, amplitude of the PhNR was increased while the
      OPs were minimally affected. CONCLUSION: With an intact a-wave demonstrated
      following ONTx, we find that the most robust indicators of RGC function in the
      mouse full-field ERG were the STR components.

PMID- 24659325
TI  - Morphological changes produced by acid dissolution in Er:YAG laser irradiated
      dental enamel.
AB  - Several scientific reports have shown the effects of Er:YAG laser irradiation on
      enamel morphology. However, there is lack of information regarding the
      morphological alterations produced by the acid attack on the irradiated surfaces.
      The aim of this study was to evaluate the morphological changes produced by acid
      dissolution in Er:YAG laser irradiated dental enamel. Forty-eight enamel samples
      were divided into four groups (n = 12). GI (control); Groups II, III, and IV were
      irradiated with Er:YAG at 100 mJ (12.7 J/cm(2) ), 200 mJ (25.5 J/cm(2) ), and 300
      mJ (38.2 J/cm(2) ), respectively, at 10 Hz without water irrigation. Enamel
      morphology was evaluated before-irradiation, after-irradiation, and after-acid
      dissolution, by scanning electron microscopy (SEM). Sample coating was avoided
      and SEM analysis was performed in a low-vacuum mode. To facilitate the location
      of the assessment area, a reference point was marked. Morphological changes
      produced by acid dissolution of irradiated enamel were observed, specifically on
      laser-induced undesired effects. These morphological changes were from mild to
      severe, depending on the presence of after-irradiation undesired effects.

PMID- 24659324
TI  - Percent free prostate-specific antigen does not improve the effectiveness of
      prostate cancer detection in Chinese men with a prostate-specific antigen of 2.5
      20.0 ng/ml: a multicenter study.
AB  - The prostate-specific antigen (PSA) "gray zone" in Chinese men is likely higher
      than the traditional value (2.5-10.0 ng/ml) since the incidence of prostate
      cancer in Chinese men is relative low. The utility of percent free PSA in
      predicting prostate cancer is based on Western populations and may introduce
      sizable bias when applied to a Chinese cohort. We assessed the efficacy of
      percent free PSA in predicting prostate cancer in Chinese men with a PSA of 2.5
      10.0 and 10.1-20.0 ng/ml. A total of 558 men with a PSA of 2.5-20.0 ng/ml who had
      undergone prostatic biopsy to detect prostate cancer from two Chinese centers
      were included. The rates of prostate cancer in different percent free PSA ranges
      were evaluated. Receiver operating characteristic curve (ROC) was used to
      evaluate and compare the efficiency of PSA and percent free PSA in the diagnosis
      of prostate cancer. The areas under ROC (AUCs) for percent free PSA for
      predicting prostate cancer were not higher than those for PSA, although prostate
      cancer detection rates increased with decreased percent free PSA in men with a
      PSA of 2.5-10.0, 10.1-20.0, and 2.5-20.0 ng/ml. Similarly, for men aged <70 and
      >= 70 years and with prostate volume <40 and >= 40 ml, AUCs showed percent free
      PSA was not better than PSA in predicting prostate cancer. By analyzing
      multicenter data, we first found that percent free PSA does not improve detection
      of prostate cancer in Chinese men with a PSA of 2.5-10.0 or 10.1-20.0 ng/ml.

PMID- 24659326
TI  - Synthesis, crystal structures and photo- and electro-luminescence of copper(I)
      complexes containing electron-transporting diaryl-1,3,4-oxadiazole.
AB  - Two mononuclear Cu(I) complexes based on 2-(2-pyridyl)benzimidazolyl derivative
      ligand containing electron-transporting 1,3,4-oxadiazole group (L),
      [Cu(L)(PPh(3))2](BF(4)) and [Cu(L)(DPEphos)](BF(4)), where L = 1-(4-(5-(4-tert
      butylphenyl)-1,3,4-oxadiazol-2-yl)benzyl)-2-(pyridin-2-yl)benzimidazole and
      DPEphos = bis[2-(diphenylphosphino)phenyl]ether, have been successfully
      synthesized and characterized. The X-ray crystal structure analyses of the ligand
      L and the complex [Cu(L)(PPh(3))2](BF(4)) were described. The photophysical
      properties of the complexes were examined by using UV-vis, photoluminescence
      spectroscopic analysis. The doped light-emitting devices using the Cu(I)
      complexes as dopants were fabricated. With no electron transporting layers
      employed in the devices, yellow electroluminescence from Cu(I) complexes were
      observed. The devices based on the complex [Cu(L)(DPEphos)](BF4) possess better
      performance as compared with the devices fabricated by the complex
      [Cu(L)(PPh(3))2](BF(4)). The devices with the structure of ITO/MoO(3) (2 nm)/NPB
      (40 nm)/CBP:[Cu(L)(DPEphos)](BF(4)) (8 wt%, 30 nm)/BCP (30 nm)/LiF (1 nm)/Al (150
      nm) exhibit a maximum efficiency of 3.04 cd/A and a maximum brightness of 4,758
      cd/m(2).

PMID- 24659327
TI  - Acquisition of spatial knowledge in different urban areas:  evidence from a
      survey analysis of adolescents.
AB  - We herein explore the perception of the geographic environment and analyse the
      mechanisms that constrain the cognitive processing of spatial information in
      general. Our guiding theoretical background assumption is that the structure of
      the spatial environment is a cognitively robust and mutually constrained
      threefold system relating (1) cognitive topology (comprised of a path and place
      structure of spatial information and constrained by reference frame-based
      factors), (2) experience-based functional knowledge (including the effects of
      socio-economic factors, frequency and familiarity) and (3) linguistic
      representations (primarily encoded in the prepositional system of a natural
      language). Here, we focus on (2), i.e. the effect of functional knowledge on the
      process of acquiring spatial knowledge. We empirically tested adolescents aged 12
      17 years to explore the interaction between frequency, familiarity and functional
      knowledge from a developmental point of view. The social factors we explore are
      precisely defined and parameterized in our results (exposure to a particular
      urban area, place of residence, gender, age and factors relating to the
      environmental and social quality of the local area). Our research shows that
      there are divergences between the so called objective topology and the cognitive
      typology of the urban environment that are significantly constrained by intensity
      of interactions with environment, number of functionally significant places
      within particular area and age from a developmental perspective in terms of
      spatial knowledge acquisition.

PMID- 24659330
TI  - Inhibition of the Arabidopsis salt overly sensitive pathway by 14-3-3 proteins.
AB  - The Salt Overly Sensitive (SOS) pathway regulates intracellular sodium ion
      (Na(+)) homeostasis and salt tolerance in plants. Until recently, little was
      known about the mechanisms that inhibit the SOS pathway when plants are grown in
      the absence of salt stress. In this study, we report that the Arabidopsis
      thaliana 14-3-3 proteins lambda and kappa interact with SOS2 and repress its
      kinase activity. Growth in the presence of salt decreases the interaction between
      SOS2 and the 14-3-3 proteins, leading to kinase activation in planta. 14-3-3
      lambda interacts with the SOS2 junction domain, which is important for its kinase
      activity. A phosphorylation site (Ser-294) is identified within this domain by
      mass spectrometry. Mutation of Ser-294 to Ala or Asp does not affect SOS2 kinase
      activity in the absence of the 14-3-3 proteins. However, in the presence of 14-3
      3 proteins, the inhibition of SOS2 activity is decreased by the Ser-to-Ala
      mutation and enhanced by the Ser-to-Asp exchange. These results identify 14-3-3
      lambda and kappa as important regulators of salt tolerance. The inhibition of
      SOS2 mediated by the binding of 14-3-3 proteins represents a novel mechanism that
      confers basal repression of the SOS pathway in the absence of salt stress. 

PMID- 24659329
TI  - Arabidopsis DELLA and JAZ proteins bind the WD-repeat/bHLH/MYB complex to
      modulate gibberellin and jasmonate signaling synergy.
AB  - Integration of diverse environmental and endogenous signals to coordinately
      regulate growth, development, and defense is essential for plants to survive in
      their natural habitat. The hormonal signals gibberellin (GA) and jasmonate (JA)
      antagonistically and synergistically regulate diverse aspects of plant growth,
      development, and defense. GA and JA synergistically induce initiation of
      trichomes, which assist seed dispersal and act as barriers to protect plants
      against insect attack, pathogen infection, excessive water loss, and UV
      irradiation. However, the molecular mechanism underlying such synergism between
      GA and JA signaling remains unclear. In this study, we revealed a mechanism for
      GA and JA signaling synergy and identified a signaling complex of the GA pathway
      in regulation of trichome initiation. Molecular, biochemical, and genetic
      evidence showed that the WD-repeat/bHLH/MYB complex acts as a direct target of
      DELLAs in the GA pathway and that both DELLAs and JAZs interacted with the WD
      repeat/bHLH/MYB complex to mediate synergism between GA and JA signaling in
      regulating trichome development. GA and JA induce degradation of DELLAs and
      JASMONATE ZIM-domain proteins to coordinately activate the WD-repeat/bHLH/MYB
      complex and synergistically and mutually dependently induce trichome initiation.
      This study provides deep insights into the molecular mechanisms for integration
      of different hormonal signals to synergistically regulate plant development. 

PMID- 24659331
TI  - Serum amyloid-A in Behcet's disease.
AB  - Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and
      previously investigated as a marker of disease activity in many rheumatologic
      disorders. Its significance in Behcet's disease (BD), a chronic inflammatory
      disorder at the crossroad between autoimmune and autoinflammatory syndromes, is
      still unraveled. Our aim was to assess the role of SAA levels as a potential
      marker of disease activity in patients with BD. According to our findings, the
      occurrence of oral aphthosis, neurological impairment, and ocular disease is
      significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L,
      respectively. We also suggest that increased SAA levels might identify a
      thrombotic risk in BD with previous or concurrent vascular involvement.

PMID- 24659332
TI  - Mean platelet volume as a surrogate marker of inflammation in systemic lupus
      erythematosus.

PMID- 24659333
TI  - Answer to: letter to the editor entitled "Uterus preservation as an alternative
      to an emergency hysterectomy for postpartum hemorrhage".

PMID- 24659334
TI  - Update on best available options in obstetrics anaesthesia: perinatal outcomes,
      side effects and maternal satisfaction. Fifteen years systematic literature
      review.
AB  - PURPOSE: In modern obstetrics, different pharmacological and non-pharmacological
      options allow to obtain pain relief during labour, one of the most important
      goals in women satisfaction about medical care. The aim of this review is to
      compare all the analgesia administration schemes in terms of effectiveness in
      pain relief, length of labour, mode of delivery, side effects and neonatal
      outcomes. METHODS: A systematic literature search was conducted in electronic
      databases in the interval time between January 1999 and March 2013. Key search
      terms included: "labour analgesia", "epidural anaesthesia during labour"
      (excluding anaesthesia for Caesarean section), "epidural analgesia and labour
      outcome" and "intra-thecal analgesia". RESULTS: 10,331 patients were analysed:
      5,578 patients underwent Epidural-Analgesia, 259 patients spinal analgesia, 2,724
      combined spinal epidural analgesia, 322 continuous epidural infusion (CEI), 168
      intermittent epidural bolus, 684 patient-controlled infusion epidural analgesia
      and 152 intra-venous patient-controlled epidural analgesia. We also considered
      341 women who underwent patient-controlled infusion epidural analgesia in
      association with CEI and 103 patients who underwent patient-controlled infusion
      epidural analgesia in association with automatic mandatory bolus. CONCLUSION: No
      significant differences occurred among all the available administration schemes
      of neuraxial analgesia. In absence of obstetrical contraindication, neuraxial
      analgesia has to be considered as the gold standard in obtaining maternal pain
      relief during labour. The options available in the administration of analgesia
      should be known and evaluated together by both gynaecologists and
      anaesthesiologists to choose the best personalized scheme and obtain the best
      women satisfaction. Since it is difficult to identify comparable circumstances
      during labour, it is complicate to standardize drugs schemes and their
      combinations.

PMID- 24659335
TI  - Aureobasidium pullulans as a source of liamocins (heavy oils) with anticancer
      activity.
AB  - Liamocins are structurally unique, heavier-than-water "oils" produced by certain
      strains of Aureobasidium pullulans. The aim of the current study is to identify
      new sources of liamocins and evaluate their potential as anticancer agents. Nine
      strains of A. pullulans from phylogenetic clades 8, 9, and 11 were examined for
      the first time for production of liamocins. Strains in these clades have only
      been isolated from tropical environments, and all strains tested here were from
      various locations in Thailand. Strains RSU 9, RSU 21, and RSU 29, all from clade
      11, produced from 7.0 to 8.6 g liamocins/l from medium containing 5 % sucrose.
      These are the highest yields of liamocins that we have found thus far. These
      strains also produced from 9.4 to 17 g pullulan/l. The structural identity of
      liamocins was confirmed by matrix-assisted laser desorption/ionization mass
      spectrometry; differential spectra were obtained in which the dominant ion was
      either at about m/z 805.5 or m/z 949.6, consistent with the structure of
      liamocins. Liamocins from A. pullulans strains RSU 9 and RSU 21 inhibited two
      human breast cancer cell lines and a human cervical cancer cell line (IC50 values
      of 32.2 +/- 1.4 to 63.1 +/- 2.4 MUg liamocins/ml) but were not toxic to a normal
      cell line. Liamocins weakly inhibited a strain of Enterococcus faecalis, but did
      not inhibit strains of Lactobacillus fermentum, Staphylococcus aureus,
      Escherichia coli, and Pseudomonas aeruginosa. Thus, A. pullulans phylogenetic
      clade 11 is a promising source of liamocins, and these compounds merit further
      examination as potential anticancer agents.

PMID- 24659336
TI  - Large-scale tag/PCR-based gene expression profiling.
AB  - An intriguing enigma in molecular biology is how genes within a single genome are
      differentially expressed in different cell types of a multicellular organism, or
      in response to different developmental or environmental queues in a single cell
      type. Quantification of transcript levels on a genome-wide scale, often termed
      transcript profiling, provides a powerful approach to identifying protein-coding
      and non-coding RNAs functionally relevant to a given biological process. Indeed,
      transcriptome analysis has been a key area of biological inquiry for decades and
      successfully produced discoveries in a multitude of processes and disease states,
      and in an increasingly large number of organisms. The evolution of technologies
      with increasing levels of informational content, ranging from hybridization-based
      technologies such as Northern blot analysis and microarrays to tag/polymerase
      chain reaction (PCR)- and sequence-based technologies including differential
      display and SAGE, along with the next-generation sequencing, has provided hope
      for revealing the molecular details of biological systems as they respond to
      change. This review is an overview of selected high throughput tag/PCR-based
      methods for genome-wide expression profiling amenable to high-throughput
      automated operation in any standard laboratory.

PMID- 24659337
TI  - Headspace stir bar sorptive extraction followed by thermal desorption and gas
      chromatography with mass spectrometry to determine musk fragrances in sludge
      samples without sample pretreatment.
AB  - A direct, simple and solvent-free method based on headspace stir bar sorptive
      extraction and thermal desorption gas chromatography with mass spectroscopy was
      developed to determine 13 musk fragrances (six polycyclic musks, three nitro
      musks and four macrocyclic musks) in sludge without sample treatment. The optimal
      headspace stir bar sorptive extraction conditions were achieved when a
      polydimethylsiloxane stir bar was exposed for 45 min in the headspace of a 10 mL
      vial filled with 100 mg of sludge mixed with 0.2 mL of water stirred at 750 rpm
      at 80 degrees C. The stir bar was then desorbed in the thermal desorption gas
      chromatography and mass spectrometry system, obtaining limits of detection
      between 5 and 30 ng/g. The method applicability was tested with sewage sludge
      from two urban wastewater treatment plants and from a potable water treatment
      plant. Results showed galaxolide and tonalide to be the most abundant musk
      fragrances found in wastewater treatment plants with maximal concentrations of
      9240 and 7500 ng/g, respectively. Maximum concentration levels between 35 and 635
      ng/g were found for musk ketone, musk moskene, traseolide, phantolide and
      celestolide in this kind of samples. Concentrations below the limits of
      quantitation of phantolide, galaxolide, tonalide and musk ketone were found in
      sludge from a potable water treatment plant. 

PMID- 24659338
TI  - Improvement and validation of d-xylose determination in urine and serum as a new
      tool for the noninvasive evaluation of lactase activity in humans.
AB  - BACKGROUND: The phloroglucinol assay is the current method for d-xylose
      determination in urine/plasma/serum. However, its sensitivity is limited when low
      amounts of d-xylose are to be measured, such as in the noninvasive evaluation of
      intestinal lactase with 4-galactosylxylose (gaxilose). An improved assay was
      therefore needed. METHODS: We developed and validated a modified version of the
      phloroglucinol-based assay for quantification of d-xylose in urine/serum samples.
      A method for gaxilose determination by gas chromatography (GC) was also
      optimized. RESULTS: Linearity ranged from 0.125 to 5.0 mg/l (5-200 mg/l in
      original sample). Accuracy at LOQ (0.125 mg/l) was 0.97/2.49% in spiked
      urine/serum; for other quality controls (QC), it was <1.27%. Intra- and
      interassay precision at LOQ were 6.02% and 6.45% for urine, and 8.86% and 10.00%,
      respectively, for serum; for other QC, precision was <2.15%. Linearity of
      gaxilose determination by GC was 3.90-195.17 for urine and 9.75-195.17 mg/l for
      serum with acceptable sensitivity and reproducibility. The method proved adequate
      for the d-xylose determination in healthy and hypolactasic subjects after oral
      administration of gaxilose. CONCLUSIONS: The modified method provides high
      sensitivity and robustness for d-xylose quantification in urine/serum for routine
      clinical use especially in the noninvasive diagnosis of intestinal lactase
      deficiency with the gaxilose test.

PMID- 24659341
TI  - Optically tunable magneto-capacitance phenomenon in organic semiconducting
      materials developed by electrical polarization of intermolecular charge-transfer
      states.

PMID- 24659339
TI  - Synergistic effects of eukaryotic coexpression plasmid carrying  LKB1 and FUS1
      genes on lung cancer in vitro and in vivo.
AB  - PURPOSE: LKB1 and FUS1 are two kinds of new tumor suppressor genes as well as
      early-stage genes in lung cancer. Recent studies showed that LKB1 and FUS1 play
      important roles in lung carcinogenesis process. We hypothesized that combined
      gene therapy with LKB1 and FUS1 could inhibit lung cancer growth and development
      synergistically. METHODS: In this study, two kinds of tumor suppressor genes,
      LKB1 and FUS1, were constructed in an eukaryotic coexpression plasmid pVITRO(2),
      and then, we evaluated the synergistic effects of the two genes on anticancer
      activity and explored the relevant molecular mechanisms. RESULTS: We defined
      coexpression of LKB1 and FUS1 could synergistically inhibited lung cancer cells
      growth,invasion and migration and induced the cell apoptosis and arrested cell
      cycle in vitro. Intratumoral administration of liposomes: pVITRO(2)-LKB1-FUS1
      complex (LPs-pVITRO(2)-LKB1-FUS1) into subcutaneous lung tumor xenograft resulted
      in more significant inhibition of tumor growth. Furthermore, intravenous
      injection of LPs-pVITRO(2)-LKB1-FUS1 into mice bearing experimental A549 lung
      metastasis demonstrated synergistic decrease in the number of metastatic tumor
      nodules. Finally, combined treatment with LKB1 and FUS1 prolonged overall
      survival in lung tumor-bearing mice. Further study showed tha tthe synergistic
      anti-lung cancer effects of coexpression ofLKB1 and FUS1 might be related to
      upregulation of p-p53, p-AMPK and downregulation of p-mTOR, p-FAK, MMPs, NEDD9,
      VEGF/R and PDGF/R. CONCLUSIONS: Our results suggest that combined therapy with
      eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes may be a novel and
      efficient treatment strategy for human lung cancer.

PMID- 24659340
TI  - Comparative study of autophagy inhibition by 3MA and CQ  on Cytarabine-induced
      death of leukaemia cells.
AB  - BACKGROUND: As the molecular mechanisms of Cytarabine,one of the most important
      drugs used in the leukaemia's treatment, are only partially understood and the
      role of autophagy on leukaemia development and treatment is only recently being
      investigated, in this study, by using Chloroquine (CQ) and 3-methyladenine (3MA)
      as autophagy inhibitors, we aim to evaluate the contribution of an autophagic
      mechanism to Cytarabine (AraC)-induced death of HL60 leukaemia cells. METHODS:
      Trypan blue exclusion and AnnexinV/PI assays were used to evaluate HL60 cell
      death under AraC treatment in the presence or absence of 3MA and CQ. Western
      blotting and immunofluorescence experiments were performed to show the
      involvement of apoptosis and autophagy protein expressions. Phenotypic
      characterization of HL60-treated cells was performed by using immunophenotyping.
      Clonogenic assays were applied to analyse clonal function of HL60-treated cells.
      RESULTS: We observed that although autophagy inhibition by 3MA, but not CQ,
      increased the death of HL60 AraC cells after 24 h of treatment, no significant
      differences between AraC and AraC + 3MA-treated groups were observed by using
      clonogenic assay. In addition, increased number of immature (CD34(+)/CD38(-)Lin(
      /low)) HL60 cells was found in AraC and AraC-3MA groups when compared with
      control untreated cells. CONCLUSIONS: Although AraC anti-leukaemia effects could
      be potentiated by 3MA autophagy inhibition after 24 h of exposure, leukaemia cell
      resistance, the main causes of treatment failure, is also promoted by autophagy
      initial stage impairment by 3MA, denoting the complex role of autophagy in
      leukaemia cells' response to chemotherapy.

PMID- 24659342
TI  - Cellular localization of CoPK12, a Ca(2+)/calmodulin-dependent protein kinase in
      mushroom Coprinopsis cinerea, is regulated by N-myristoylation.
AB  - Multifunctional Ca(2+)/calmodulin-dependent protein kinases (CaMKs) have been
      extensively studied in mammals, whereas fungus CaMKs still remain largely
      uncharacterized. We previously obtained CaMK homolog in Coprinopsis cinerea,
      designated CoPK12, and revealed its unique catalytic properties in comparison
      with the mammalian CaMKs. To further clarify the regulatory mechanisms of CoPK12,
      we investigated post-translational modification and subcellular localization of
      CoPK12 in this study. In C. cinerea, full-length CoPK12 (65 kDa) was fractionated
      in the membrane fraction, while the catalytically active fragment (46 kDa) of
      CoPK12 was solely detected in the soluble fraction by differential
      centrifugation. Expressed CoPK12-GFP was localized on the cytoplasmic and
      vacuolar membranes as visualized by green fluorescence in yeast cells. In vitro N
      myristoylation assay revealed that CoPK12 is N-myristoylated at Gly-2 in the N
      terminal position. Furthermore, calmodulin could bind not only to CaM-binding
      domain but also to the N-terminal myristoyl moiety of CoPK12. These results,
      taken together, suggest that the cellular localization and function of CoPK12 are
      regulated by protein N-myristoylation and limited proteolysis.

PMID- 24659343
TI  - Update on HIV in Western Europe.
AB  - HIV infection in Western Europe is mainly concentrated among men who have sex
      with men, heterosexuals who acquired HIV from sub-Saharan African countries, and
      in people who inject drugs. The rate of newly diagnosed cases of HIV has remained
      roughly stable since 2004 whereas the number of people living with HIV has slowly
      increased due to new infections and the success of antiretroviral therapy in
      prolonging life. An ageing population is gradually emerging that will require
      additional care. There are large differences across countries in HIV testing
      rates, proportions of people who present to care with low CD4+ cell counts,
      accessibility to treatment and care, and rates of retention once in care.
      Improved collection of HIV surveillance data will benefit countries and help to
      understand their epidemic better. However, social inequalities experienced by
      people with HIV still remain in some regions and urgently need to be addressed.

PMID- 24659345
TI  - Editorial-sea urchin special issue.

PMID- 24659344
TI  - A lifecycle approach to HIV prevention in African women and children.
AB  - Effective biomedical and structural HIV prevention approaches are being
      implemented throughout sub-Saharan Africa. A "lifecycle approach" to HIV
      prevention recognizes the interconnectedness of the health of women, children and
      adolescents, and prioritizes interventions that have benefits across these
      populations. We review new biomedical prevention strategies for women,
      adolescents and children, structural prevention approaches, and new modalities
      for eliminating infant HIV infection, and discuss the implications of a lifecycle
      approach for the success of these methods. Some examples of the lifecycle
      approach include evaluating education and HIV prevention strategies among
      adolescent girls not only for their role in reducing risk of HIV infection and
      early pregnancy, but also to promote healthy adolescents who will have healthier
      future children. Similarly, early childhood interventions such as exclusive
      breastfeeding not only prevent HIV, but also contribute to better child and
      adolescent health outcomes. The most ambitious biomedical infant HIV prevention
      effort, Option B+, also represents a lifecycle approach by leveraging the
      prevention benefits of optimal HIV treatment for mothers; maternal survival
      benefits from Option B+ may have ultimately more health impact on children than
      the prevention of infant HIV in isolation. The potential for synergistic and
      additive benefits of lifecycle interventions should be considered when scaling up
      HIV prevention efforts in sub-Saharan Africa.

PMID- 24659346
TI  - Assessment of ecosystem health and ecotoxicology through  chemical analysis and
      modeling.

PMID- 24659347
TI  - Toxicity of differently sized and coated silver nanoparticles  to the bacterium
      Pseudomonas putida: risks for the aquatic  environment?
AB  - Aim of this study was to describe the toxicity of a set of different commercially
      available silver nanoparticles (AgNPs) to the gram-negative bacterium Pseudomonas
      putida (growth inhibition assay, ISO 10712) in order to contribute to their
      environmental hazard and risk assessment. Different AgNP sizes and coatings were
      selected in order to analyze whether those characteristics are determinants of
      nanoparticle toxicity. Silver nitrate was tested for comparison. In general
      Pseudomonas putida reacted very sensitive towards the exposure to silver, with an
      EC05 value of 0.043 MUg L-1 for AgNO3 and between 0.13 and 3.41 MUg L-1 for the
      different AgNPs (EC50 values 0.16 MUg L-1 for AgNO3, resp. between 0.25 and 13.4
      MUg L-1 for AgNPs). As the ionic form of silver is clearly the most toxic, an
      environmental hazard assessment for microorganisms based on total silver
      concentration and the assumption that AgNPs dissolve is sufficiently protective.
      Neither specific coatings nor certain sizes could be linked to increasing or
      decreasing toxicity. The characterization of particle behavior as well as the
      total and dissolved silver content in the medium during the exposures was not
      possible due to the high sensitivity of Pseudomonas (test concentrations were
      below detection limits), indicating the need for further development in the
      analytical domain. Monitored silver concentrations in the aquatic environment
      span six orders of magnitude (0.1-120,000 ng L-1), which falls into the span of
      observed EC05 values and might hence indicate a risk to environmental bacteria.

PMID- 24659349
TI  - Consumer acceptance of quality protein maize (QPM) in East Africa.
AB  - BACKGROUND: Undernutrition in sub-Saharan Africa remains problematic, and quality
      protein maize (QPM) can benefit populations whose diets are heavily based on
      maize and who are consequently at risk for inadequate intakes of quality protein.
      However, changes in the chemical composition of QPM may affect its sensory
      characteristics and, hence, acceptance. Acceptance tests were therefore conducted
      to evaluate QPM varieties in three East African countries using central location
      tests with one or two varieties in each country, using the most popular
      preparations: ugali (Tanzania), githeri (Kenya) and injera (Ethiopia). In total,
      281 urban and rural consumers of both sexes and varying levels of education
      evaluated the products on standard sensory criteria: appearance, aroma, texture,
      taste and overall, using a Likert scale. RESULTS: The results show that African
      consumers can differentiate QPM products from their conventional counterparts,
      indicating that the QPM trait results in distinguishable sensory changes.
      Analysis by ordinal mixed regression models showed that consumers found QPM
      acceptable and even preferable to conventional maize. CONCLUSION: The sensory
      characteristics of QPM are therefore no impediment to its adoption; on the
      contrary, when coupled with good agronomic performance, they may help its
      utilization, leading to a positive impact in nutritionally vulnerable
      populations.

PMID- 24659348
TI  - Lipopolysaccharides upregulate hepcidin in neuron via microglia and the IL
      6/STAT3 signaling pathway.
AB  - Neuroinflammation is closely related to brain iron homeostasis. Our previous
      study demonstrated that lipopolysaccharides (LPS) can regulate expression of iron
      regulatory peptide hepcidin; however, the mechanism is undefined. Here, we
      demonstrated that intracerebroventricular injection of LPS in rat brain
      upregulated hepcidin and downregulated ferroportin 1 in the cortex and substantia
      nigra. LPS increased hepcidin expression in neurons only when they were co
      cultured with BV-2 microglia, and the upregulation was suppressed by IL-6
      neutralizing antibody in vitro. In addition, IL-6 but not IL-1alpha, IL-1beta, or
      tumor necrosis factor-alpha increased hepcidin expression and signal transducer
      and activator of transcription 3 (STAT3) phosphorylation in cortical neurons and
      MES23.5 dopaminergic neurons. These effects were blocked by the STAT3 inhibitor,
      stattic. Our results show that neurons are the major source of increased hepcidin
      expression in response to LPS challenge but microglia play a key mediator role by
      releasing IL-6 and recruiting the STAT3 pathway. We conclude that LPS upregulates
      hepcidin expression in neurons via microglia and the IL-6/STAT3 signaling
      pathway.

PMID- 24659350
TI  - Rise and fall of glycoprotein IIb-IIIa inhibitors in ST-segment elevation
      myocardial infarction.

PMID- 24659351
TI  - Small retinal haemorrhages accompanied by macular soft drusen: prevalence, and
      funduscopic and angiographic characteristics.
AB  - PURPOSE: To investigate the prevalence and clinical significance of small retinal
      haemorrhages accompanied by macular soft drusen in exudative age-related macular
      degeneration (AMD). METHODS: This observational case series included patients who
      had first been diagnosed with exudative AMD. Small retinal haemorrhages were
      defined as preretinal or intraretinal haemorrhages, no larger than half the disc
      diameter in size and located within 3000 MUm of the fovea centre. If there was
      more than one haemorrhage, the entire affected area was less than two-thirds of
      the disc diameter. Macular soft drusen was defined as the presence of soft drusen
      (>=125 MUm in diameter) within the macular area. The presence of retinal
      angiomatous proliferation (RAP) was estimated based on the results of indocyanine
      green angiography (ICGA). The prevalence of reticular pseudodrusen was also
      estimated. RESULTS: Among the 1921 eyes from 1604 patients who were newly
      diagnosed with exudative AMD during the 40 months prior to the study, 101 eyes
      (5.3%) from 79 patients presented with the fundus characteristics described
      above. ICGA images were available for 69 eyes. Among these eyes, 28 eyes (43.1%)
      and 25 eyes (38.5%) were found to have type 1 and 2 RAP, respectively. A
      chorioretinal anastomosis (type 3 RAP) was identified in 12 (18.5%) eyes.
      Reticular pseudodrusen were noted in 78 eyes (77.2%). CONCLUSIONS: The presence
      of small retinal haemorrhages accompanied by macular soft drusen was highly
      predictive of RAP. The high prevalence of both soft drusen and reticular
      pseudodrusen in these eyes may suggest a profound decrease in choroidal perfusion
      in these eyes.

PMID- 24659352
TI  - Pre-Descemet's endothelial keratoplasty (PDEK).
AB  - A new surgical technique for endothelial keratoplasty is described, in which the
      composite of pre-Descemet's layer (Dua's layer) with Descemet's membrane and
      endothelium is transplanted subsequent to the removal of the recipient's
      Descemet's membrane. The technique was performed in five eyes of five patients,
      with successful attachment of the graft and good postoperative visual recovery in
      all cases. Postoperative optical coherence tomography showed good graft
      attachment without interface abnormalities and a mean graft thickness was 28+/
      5.6 MUm. This study demonstrates the practicality of the technique, termed pre
      Descemet's endothelial keratoplasty (PDEK), which can be a viable option in
      endothelial keratoplasty with some potential advantages.

PMID- 24659353
TI  - Decreased subfoveal choroidal thickness and failure of emmetropisation in
      patients with oculocutaneous albinism.
AB  - PURPOSE: The purpose of this work was to describe the choroidal structure in
      patients with oculocutaneous albinism (OCA). METHODS: 20 eyes of 10 patients with
      OCA and 14 eyes of 7 healthy controls were recruited for the study. Enhanced
      depth imaging optical coherence tomography (OCT) images of the subjects were
      taken. The choroidal thickness (CT) was measured from the outer boarder of the
      retinal pigment epithelium to the inner boarder of sclera at 500 um intervals of
      a horizontal section from the optic disc. Statistical analysis was performed to
      evaluate variations in CT at subfoveal and peripapillary areas. RESULTS: In the
      fundoscopic examination and OCT imaging, the foveal light reflex was absent and
      the foveal pit could not be observed in all of the patients with OCA. The mean
      subfoveal CT of the patients with OCA was significantly thinner (242+/-56 um)
      compared with healthy controls (349+/-70 um) (p<0.001); while there was no
      statistically significant difference in the peripapillary CTs of the patients
      with OCA and controls (157+/-42 um vs 151+/-31 um respectively, p=0.77),
      indicating a localised abnormality of choroidal anatomy. CONCLUSIONS: This study
      for the first time demonstrated that CT is decreased in patients with OCA at the
      subfoveal region. These data combined with the underdevelopment of the foveal pit
      indicate that there is a generalised developmental or genetic abnormality in the
      posterior pole of patients with OCA. This choroidal structural abnormality might
      be related to the previously reported failure of emmetropisation in these
      children. Further research is needed to understand choroidal metabolism and its
      relationship with these anatomical changes in albinism.

PMID- 24659354
TI  - Swept-source optical coherence tomography imaging of the cortical vitreous and
      the vitreoretinal interface in proliferative diabetic retinopathy: assessment of
      vitreoschisis, neovascularisation and the internal limiting membrane.

PMID- 24659355
TI  - Post-operative neck ultrasound and risk stratification in differentiated thyroid
      cancer patients with initial lymph node involvement.
AB  - OBJECTIVE: Cervical ultrasound (US) scan is a key tool for detecting metastatic
      lymph nodes (N1) in patients with papillary thyroid cancer (PTC). N1-PTC patients
      are stratified as intermediate-risk and high-risk (HR) patients, according to the
      American Thyroid Association (ATA) and European Thyroid Association (ETA)
      respectively. The aim of this study was to assess the value of post-operative
      cervical US (POCUS) in local persistent disease (PD) diagnosis and in the
      reassessment of risk stratification in N1-PTC patients. DESIGN: Retrospective
      cohort study. METHODS: Between 1997 and 2010, 638 N1-PTC consecutive patients
      underwent a systematic POCUS. Sensitivity, specificity, negative predictive value
      (NPV), and positive predictive value (PPV) of POCUS for the detection of PD were
      evaluated and a risk reassessment using cumulative incidence functions was
      carried out. RESULTS: After a median follow-up of 41.6 months, local recurrence
      occurred in 138 patients (21.6%), of which 121 were considered to have PD.
      Sensitivity, specificity, NPV, and PPV of POCUS for the detection of the 121 PD
      were 82.6, 87.4 95.6, and 60.6% respectively. Cumulative incidence of recurrence
      at 5 years was estimated at 26% in ETA HR patients, 17% in ATA intermediate-risk
      patients, and 35% in ATA HR patients respectively. This risk fell to 9, 8, and
      11% in the above three groups when the POCUS result was normal and to <6% when it
      was combined with thyroglobulin results at ablation. CONCLUSION: POCUS is useful
      for detecting PD in N1-PTC patients and for stratifying individual recurrence
      risk. Its high NPV could allow clinicians to tailor follow-up recommendations to
      individual needs.

PMID- 24659356
TI  - Comparison of three chromatographic techniques for the detection of mitragynine
      and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants.
AB  - Leaves of the Southeast Asian plant Mitragyna speciosa are used to suppress pain
      and mitigate opioid withdrawal syndromes. The potential threat of abuse and ready
      availability of this uncontrolled psychoactive plant have led to the need for
      improved analytical techniques for the detection of the major active components,
      mitragynine and 7-hydroxymitragynine. Three independent chromatographic methods
      coupled to two detection systems, GC with MS, supercritical fluid chromatography
      with diode array detection, and HPLC with MS and diode array detection, were
      compared for the analysis of mitragynine and other indole and oxindole alkaloids
      in M. speciosa plants. The indole alkaloids included two sets of
      diastereoisomers: (i) paynantheine and 3-isopaynantheine and (ii) mitragynine,
      speciogynine, and speciociliatine. Two oxindole alkaloid diastereoisomers,
      corynoxine and corynoxine B, were also studied. The HPLC and supercritical fluid
      chromatography methods successfully resolved the major components with slightly
      different elution orders. The GC method was less satisfactory because it was
      unable to resolve mitragynine and speciociliatine. This separation was difficult
      by GC with a liquid stationary phase because these diastereoisomers differ only
      in the orientation of an interior hydrogen atom. The observed lack of resolution
      of the indole alkaloid diastereoisomers coupled with the likeness of the mass and
      tandem mass spectra, calls into question proposed GC methods for the analysis of
      mitragynine based on solely GC with MS separation and identification. 

PMID- 24659357
TI  - Terbutaline pump maintenance therapy after threatened preterm labour for reducing
      adverse neonatal outcomes.
AB  - BACKGROUND: After successful inhibition of threatened preterm labour women are at
      high risk of recurrent preterm labour. Terbutaline pump maintenance therapy has
      been used to reduce adverse neonatal outcomes. This review replaces an earlier
      Cochrane review, published in 2002, which is no longer being updated by the team.
      OBJECTIVES: To determine the effectiveness of terbutaline pump maintenance
      therapy after threatened preterm labour in reducing adverse neonatal outcomes.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 January 2014) and reference lists of retrieved studies. SELECTION
      CRITERIA: Randomised controlled trials comparing terbutaline pump therapy with
      alternative therapy, placebo, or no therapy after arrest of threatened preterm
      labour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      the studies for inclusion and then extracted data as eligible for inclusion in
      qualitative and quantitative synthesis (meta-analysis). MAIN RESULTS: Four
      studies were included with a total of 234 women randomised. The overall
      methodological quality of the included studies was mixed; two studies provided
      very little information on study methods, there was high sample attrition in one
      study and in three studies the risk of performance bias was high. We found no
      strong evidence that terbutaline maintenance therapy offered any advantages over
      saline placebo or oral terbutaline maintenance therapy in reducing adverse
      neonatal outcomes by prolonging pregnancy among women with arrested preterm
      labour. The mean difference (MD) for gestational age at birth was -0.14 weeks
      (95% confidence interval (CI) -1.66 to 1.38) for terbutaline pump therapy
      compared with saline placebo pump for two trials combined. One trial reported a
      risk ratio (RR) of 1.17 (95% CI 0.79 to 1.73) for preterm birth (less than 37
      completed weeks) and a RR of 0.97 (95% CI 0.51 to 1.84) of very preterm birth
      (less than 34 completed weeks) for terbutaline pump compared with saline placebo
      pump. We found no evidence that terbutaline pump therapy was associated with
      statistically significant reductions in infant respiratory distress syndrome, or
      neonatal intensive care unit admission compared with placebo. Compared with oral
      terbutaline, we found no evidence that pump therapy increased the rate of therapy
      continuation, or reduced the rate of infant complications or maternal hospital re
      admissions. One study suggested that pump therapy resulted in significantly
      increased weekly cost/woman, $580 versus $12.50 (P < 0.01). No data were reported
      on long-term infant outcomes. AUTHORS' CONCLUSIONS: We found no evidence that
      terbutaline pump maintenance therapy decreased adverse neonatal outcomes. Taken
      together with the lack of evidence of benefit, its substantial expense and the
      lack of information on the safety of the therapy do not support its use in the
      management of arrested preterm labour. Future use should only be in the context
      of well-conducted, adequately powered randomised controlled trials.

PMID- 24659358
TI  - Cross-cultural adaptation of the German version of the spinal  stenosis measure.
AB  - PURPOSE: To validate the German version of the spinal stenosis measure (SSM), a
      disease-specific questionnaire assessing symptom severity, physical function, and
      satisfaction with treatment in patients with lumbar spinal stenosis. METHODS:
      After translation, cross-cultural adaptation, and pilot testing, we assessed
      internal consistency, test-retest reliability, construct validity, and
      responsiveness of the SSM subscales. Data from a large Swiss multi-center
      prospective cohort study were used. Reference scales for the assessment of
      construct validity and responsiveness were the numeric rating scale, pain
      thermometer, and the Roland Morris Disability Questionnaire. RESULTS: One hundred
      and eight consecutive patients were included in this validation study, recruited
      from five different centers. Cronbach's alpha was above 0.8 for all three
      subscales of the SSM. The objectivity of the SSM was assessed using a partial
      credit approach. The model showed a good global fit to the data. Of the 108
      patients 78 participated in the test-retest procedure. The ICC values were above
      0.8 for all three subscales of the SSM. Correlations with reference scales were
      above 0.7 for the symptom and function subscales. For satisfaction subscale, it
      was 0.66 or above. Clinically meaningful changes of the reference scales over
      time were associated with significantly more improvement in all three SSM
      subscales (p < 0.001). Conclusion: The proposed version of the SSM showed very
      good measurement properties and can be considered validated for use in the German
      language.

PMID- 24659359
TI  - Using the National HIV Behavioral Surveillance System to inform HIV prevention
      efforts in the United States.
AB  - The National HIV Behavioral Surveillance system (NHBS) was designed to monitor
      HIV prevalence and risk factors for infection among higher-risk individuals,
      i.e., sexually active men who have sex with men who attend venues, injection drug
      users who injected in the past 12 months, and heterosexuals living in low
      socioeconomic urban areas. These groups were selected as priorities for
      behavioral surveillance since they represent the major HIV transmission routes
      and the populations with the highest HIV burden. NHBS contributes to the nation's
      program of HIV surveillance by being the only multi-site population-based system
      that provides estimates on key HIV prevention measures among high-risk HIV
      negative individuals, HIV-positive individuals unaware of their infection, and
      HIV-positive individuals aware of their infection who are in and out of care.
      Accurate and precise data on the behaviors in these populations are critical for
      tracking the epidemic, planning effective responses, and monitoring and
      evaluating those responses. Reports in this supplement illustrate the uses of
      NHBS data at the national and local level and reflect ongoing efforts to improve
      the system and remains essential for characterizing and monitoring the burden of
      HIV infection and sexual and behavioral risks.

PMID- 24659361
TI  - Sex workers and their clients among Australian gay and bisexual men.
AB  - The prevalence and factors associated with being paid and paying for sex were
      explored in an online sample of Australian gay men. Sexual risk behavior among
      male sex workers and their clients was mainly related to being more sexually
      adventurous in general rather than male-to-male sex work specifically.

PMID- 24659360
TI  - The impact of community mobilisation on HIV prevention in middle and low income
      countries: a systematic review and critique.
AB  - While community mobilisation (CM) is increasingly advocated for HIV prevention,
      its impact on measurable outcomes has not been established. We performed a
      systematic review of the impact of CM within HIV prevention interventions (N =
      20), on biomedical, behavioural and social outcomes. Among most at risk groups
      (particularly sex workers), the evidence is somewhat consistent, indicating a
      tendency for positive impact, with stronger results for behavioural and social
      outcomes than for biomedical ones. Among youth and general communities, the
      evidence remains inconclusive. Success appears to be enhanced by engaging groups
      with a strong collective identity and by simultaneously addressing the socio
      political context. We suggest that the inconclusiveness of the findings reflects
      problems with the evidence, rather than indicating that CM is ineffective. We
      discuss weaknesses in the operationalization of CM, neglect of social context,
      and incompatibility between context-specific CM processes and the aspiration of
      review methodologies to provide simple, context-transcending answers. 

PMID- 24659362
TI  - Micro-CT measurements of tumoral vessels supplied by portal circulation in
      hepatic colorectal metastasis mouse model.
AB  - The purpose of this study was to elucidate the micro CT findings of tumoral
      vessels supplied by portal circulation during establishment of hepatic metastasis
      of colorectal cancer in a mouse model. Hepatic metastases were induced in 15
      BALB/c mice through the injection of murine colonic adenocarcinoma tumor cells
      into the mesenteric vein. Micro-CT imaging of the tumoral vessels was obtained to
      clarify the microvascular architecture. We evaluated the sinusoidal structure,
      diameter of the tumoral vessels (DTV) and blood vessel density (BVD) according to
      tumor sizes ranging from 201 to 3,000 um in diameter. A total of 116 tumors were
      observed on day 15 after cell injection. The mean diameter of a normal hepatic
      sinusoid was 11.7 +/- 2.0 um on micro CT. The DTV supplied by the portal vein of
      tumors measuring 1,001-1,500 um in diameter was greater than that of tumors 200
      1,000 um in diameter. The mean BVD from the portal vein gradually decrease
      according to size of tumor from 201 to 3,000 um in diameter (r(2)  = -0.584, P <
      0.01). The characteristics of tumoral vessels supplied by portal circulation
      during establishment of hepatic colorectal metastases were well visualized with
      micro-CT imaging.

PMID- 24659363
TI  - The effect of memantine on functional recovery of the facial nerve after crush
      injury.
AB  - The objective of this study is to establish whether memantine is an alternative
      and effective treatment on facial nerve recovery after crush injury, and also to
      analyze the effective doses of this promising agent. This is a randomized
      controlled animal study. 40 rats underwent crush injury to left main trunk of the
      facial nerve, and divided into 4 groups; (1) control (saline treated), (2) 5
      mg/kg memantine, (3) 10-mg/kg memantine, and (4) 20-mg/kg memantine group. Facial
      nerve functions were evaluated by eye reflex, and whisker movement compared to
      the unaffected side. They were scored on a 3-point scale. On day 28, the rats
      were sacrificed, and the facial nerves were dissected. The paraffin sections were
      studied with caspase-3 immunostaining. According to statistical data, the
      recovery in Group 4 began significantly earlier than the other groups on the
      basis of restoring eye blink reflexes and whisker movement. Groups 2 and 3 showed
      faster recovery than Group 1 on the basis of whisker movement. The caspase-3
      positive staining was rarely detected in all groups. The Kruskal-Wallis test
      revealed that Group 4 showed fewer apoptotic cells than other groups; this was
      statistically significant. However, the Mann-Whitney U test with the Bonferroni
      correction did not reveal any significant difference between the groups. In
      conclusion, this study revealed that memantine acted to restore facial nerve
      functions, and accelerate recovery after facial nerve injury by inhibiting
      apoptosis.

PMID- 24659364
TI  - Evaluation of a minimally invasive surgical fixation technique for young children
      with the Concerto Pin cochlear implant system.
AB  - In 2011, Med-El (Innsbruck, Austria) introduced a new cochlear implant system,
      designed to require a minimally invasive surgical technique and allow greater
      positional flexibility for its fixation on the skull. The Concerto Pin implant
      system is a good option for patients with thinner bone, such as children and
      elderly. The aim of this study was to investigate the implant's stability in
      children using our minimally invasive surgical technique. This was a prospective,
      longitudinal study with a single-subject, repeated-examination design. Six
      children, implanted with a Concerto Pin using our minimally invasive surgical
      technique between October 2011 and September 2012, were assessed 1, 3 and 6
      months after surgery. In each case, the implant remained in a stable position and
      no adverse events or problems with healing were observed at any time during the
      investigation. The minimally invasive technique and the method of implant
      fixation that bypass drilling a deep implant bed constitute a good option for
      patients with thinner bone, such as children. This clinical study shows the
      safety and stability of the Concerto Pin implant system using a minimally
      invasive surgical technique.

PMID- 24659365
TI  - Factors influencing the incidence of sinusitis in nasopharyngeal carcinoma
      patients after intensity-modulated radiation therapy.
AB  - The aim of the study was to investigate the incidence of sinusitis in
      nasopharyngeal carcinoma (NPC) patients before and after intensity-modulated
      radiation therapy (IMRT) and to analyze factors associated with the incidence of
      sinusitis following IMRT. We retrospectively analyzed 283 NPC patients who
      received IMRT in our hospital from March 2009 to May 2011. The diagnostic
      criteria for sinusitis are based on computed tomography (CT) or magnetic
      resonance imaging (MRI) findings. CT or MRI scans were performed before and after
      IMRT to evaluate the incidence of sinusitis. Factors influencing the incidence of
      sinusitis were analyzed by log-rank univariate and logistic multivariate
      analyses. Among the 283 NPC patients, 128 (45.2 %) suffered from sinusitis before
      radiotherapy. The incidence rates of sinusitis in patients with T1, T2, T3, and
      T4 NPC before radiotherapy were 22.6, 37.5, 46.8, and 61.3 %, respectively (chi 2
      = 14.548, p = 0.002). Among the 155 NPC patients without sinusitis before
      radiotherapy, the incidence rates of sinusitis at the end of radiotherapy and at
      1, 3, 6, 9, 12, and 18 months after radiotherapy were 32.9, 43.2, 61.3, 68.4,
      73.5, 69.7, and 61.3 %, respectively (chi 2 = 86.461, p < 0.001). Univariate
      analysis showed that T stage, invasion of the nasal cavity, nasal irrigation, and
      radiation dose to the nasopharynx were associated with the incidence of sinusitis
      in NPC patients after IMRT (p = 0.003, 0.006, 0.002, and 0.020). Multivariate
      analysis showed that T stage, invasion of the nasal cavity, and nasal irrigation
      were influential factors for the incidence of sinusitis in NPC patients after
      IMRT (p = 0.002, 0.002, and 0.000). There was a higher incidence of sinusitis
      with higher T stage among NPC patients before radiotherapy, and the incidence of
      sinusitis in NPC patients after IMRT was high (45.2 %). The incidence of
      sinusitis increased rapidly within the first 3 months after IMRT, and the number
      of sinusitis cases peaked at 6-9 months after IMRT and showed a trend toward
      stabilization after 1 year. Advanced T stage, invasion of the nasal cavity, and
      nasal irrigation were positively associated with the incidence of sinusitis in
      NPC patients after IMRT.

PMID- 24659366
TI  - Digoxin immunoassays on the ARCHITECT i2000SR and ARCHITECT c8000 analyzers are
      free from interferences of Asian, Siberian, and American ginseng.
AB  - Asian, Siberian, and American ginseng are known to interfere with serum digoxin
      measurements using fluorescence polarization technology, Digoxin II and Digoxin
      III assays (Abbott Laboratories, Green oaks, IL) as well as other digoxin assays.
      Abbott Laboratories more recently launched two new digoxin assays: iDigoxin, a
      chemiluminescent microparticle immunoassay for application on the ARCHITECT
      i1000SR and i2000SR immunoassay analyzers, and cDigoxin, a particle-enhanced
      turbidimetric inhibition immunoassay for application on the ARCHITECT c4000,
      c8000, and c1600 clinical chemistry analyzers; and we studied potential
      interferences of ginsengs with these two assays in vitro. When aliquots of drug
      free serum pool treated with activated charcoal were supplemented with extracts
      of various ginsengs, no significant apparent digoxin values were observed. In
      addition, when aliquots of the digoxin pool prepared from patients taking digoxin
      were further supplemented with these ginseng extracts and the digoxin values were
      re-measured, we observed no statistically significant difference in observed
      digoxin values compared to the original digoxin value of the pool. These results
      further establish that relatively new digoxin assays for application on the
      ARCHITECT analyzers that employ specific monoclonal antibodies against digoxin
      are free from interferences from Asian, Siberian, and American ginseng. 

PMID- 24659367
TI  - The role of miR-148a in gastric cancer.
AB  - PURPOSE: Gastric cancer is one of the most common malignant diseases worldwide,
      although much progress has been achieved in recent years, the early diagnosis and
      treatment for gastric cancer are not yet satisfactory and, thus the prognosis is
      still poor. MicroRNAs (miRNAs) can regulate a variety of physiological and
      developmental processes, it has been revealed that many miRNAs contribute the
      initiation and progression of various cancers. MiR-148a is one of the most
      important miRNAs in gastric cancer, and the aim of this paper is to provide an
      overview of various roles of miR-148a in gastric cancer. METHODS AND RESULTS: We
      searched studies in electronic databases. MiR-148a was down-regulated in gastric
      cancer tissues and cell lines, which was resulted from the hypermethylation in
      its promoter region. Furthermore, miR-148a could regulate several different
      target genes and pathways involving tumor proliferation, invasion and metastasis.
      CONCLUSION: MiR-148a may serve as a novel biomarker for the diagnosis and as a
      new therapeutic target in gastric cancer.

PMID- 24659368
TI  - The impact of left ventricular hypertrophy on survival in candidates for liver
      transplantation.
AB  - Left ventricular hypertrophy (LVH) occurs in 12% to 30% of patients with
      cirrhosis; however, its prognostic significance is not well studied. We assessed
      the association of LVH with survival in patients undergoing a liver
      transplantation (LT) evaluation. We performed a multicenter cohort study of
      patients undergoing an evaluation for LT. LVH was defined with transthoracic
      echocardiography. The outcome of interest was all-cause mortality. LVH was
      present in 138 of 485 patients (28%). Patients with LVH were older, more likely
      to be male and African American, and were more likely to have hypertension. Three
      hundred forty-five patients did not undergo transplantation (212 declined, and
      133 were waiting): 36 of 110 patients with LVH (33%) died, whereas 57 of 235
      patients without LVH (24%) died (P = 0.23). After LT, 8 of 28 patients with LVH
      (29%) died over the course of 3 years, whereas 9 of 112 patients without LVH (8%)
      died (P = 0.007). This finding was independent of conventional risk factors for
      LVH, and all deaths for patients with LVH occurred within 9 months of LT. No
      clinical or demographic characteristics were associated with mortality among LVH
      patients. In conclusion, the presence of LVH is associated with an early increase
      in mortality after LT, and this is independent of conventional risk factors for
      LVH. Further studies are needed to confirm these findings and identify factors
      associated with mortality after transplantation to improve outcomes.

PMID- 24659369
TI  - Analyses of model fit and robustness. A new look at the PISA scaling model
      underlying ranking of countries according to reading literacy.
AB  - This paper addresses methodological issues that concern the scaling model used in
      the international comparison of student attainment in the Programme for
      International Student Attainment (PISA), specifically with reference to whether
      PISA's ranking of countries is confounded by model misfit and differential item
      functioning (DIF). To determine this, we reanalyzed the publicly accessible data
      on reading skills from the 2006 PISA survey. We also examined whether the ranking
      of countries is robust in relation to the errors of the scaling model. This was
      done by studying invariance across subscales, and by comparing ranks based on the
      scaling model and ranks based on models where some of the flaws of PISA's scaling
      model are taken into account. Our analyses provide strong evidence of misfit of
      the PISA scaling model and very strong evidence of DIF. These findings do not
      support the claims that the country rankings reported by PISA are robust. 

PMID- 24659370
TI  - Information matrices and standard errors for MLEs of item parameters in IRT.
AB  - The paper clarifies the relationship among several information matrices for the
      maximum likelihood estimates (MLEs) of item parameters. It shows that the process
      of calculating the observed information matrix also generates a related matrix
      that is the middle piece of a sandwich-type covariance matrix. Monte Carlo
      results indicate that standard errors (SEs) based on the observed information
      matrix are robust to many, but not all, conditions of model/distribution
      misspecifications. SEs based on the sandwich-type covariance matrix perform most
      consistently across conditions. Results also suggest that SEs based on other
      matrices are either not consistent or perform not as robust as those based on the
      sandwich-type covariance matrix or the observed information matrix. 

PMID- 24659371
TI  - A speeded item response model: leave the harder till later.
AB  - A speeded item response model is proposed. We consider the situation where
      examinees may retain the harder items to a later test period in a time limit
      test. With such a strategy, examinees may not finish answering some of the harder
      items within the allocated time. In the proposed model, we try to describe such a
      mechanism by incorporating a speeded-effect term into the two-parameter logistic
      item response model. A Bayesian estimation procedure of the current model using
      Markov chain Monte Carlo is presented, and its performance over the two-parameter
      logistic item response model in a speeded test is demonstrated through
      simulations. The methodology is applied to physics examination data of the
      Department Required Test for college entrance in Taiwan for illustration. 

PMID- 24659372
TI  - Bayesian hierarchical multivariate formulation with factor analysis for nested
      ordinal data.
AB  - This article devises a Bayesian multivariate formulation for analysis of ordinal
      data that records teacher classroom performance along multiple dimensions to
      assess aspects characterizing good instruction. Study designs for scoring
      teachers seek to measure instructional performance over multiple classroom
      measurement event sessions at varied occasions using disjoint intervals within
      each session and employment of multiple ratings on intervals scored by different
      raters; a design which instantiates a nesting structure with each level
      contributing a source of variation in recorded scores. We generally possess
      little a priori knowledge of the existence or form of a sparse generating
      structure for the multivariate dimensions at any level in the nesting that would
      permit collapsing over dimensions as is done under univariate modeling. Our
      approach composes a Bayesian data augmentation scheme that introduces a latent
      continuous multivariate response linked to the observed ordinal scores with the
      latent response mean constructed as an additive multivariate decomposition of
      nested level means that permits the extraction of de-noised continuous teacher
      level scores and the associated correlation matrix. A semi-parametric extension
      facilitates inference for teacher-level dependence among the dimensions of
      classroom performance under multi-modality induced by sub-groupings of rater
      perspectives. We next replace an inverse Wishart prior specified for the teacher
      covariance matrix over dimensions of instruction with a factor analytic structure
      to allow the simultaneous assessment of an underlying sparse generating
      structure. Our formulation for Bayesian factor analysis employs parameter
      expansion with an accompanying post-processing sign re-labeling step of factor
      loadings that together reduce posterior correlations among sampled parameters to
      improve parameter mixing in our Markov chain Monte Carlo (MCMC) scheme. We
      evaluate the performance of our formulation on simulated data and make an
      application for the assessment of the teacher covariance structure with a dataset
      derived from a study of middle and high school algebra teachers. 

PMID- 24659373
TI  - An inequality for correlations in unidimensional monotone latent variable models
      for binary variables.
AB  - It is shown that a unidimensional monotone latent variable model for binary items
      implies a restriction on the relative sizes of item correlations: The negative
      logarithm of the correlations satisfies the triangle inequality. This inequality
      is not implied by the condition that the correlations are nonnegative, the
      criterion that coefficient H exceeds 0.30, or manifest monotonicity. The
      inequality implies both a lower bound and an upper bound for each correlation
      between two items, based on the correlations of those two items with every
      possible third item. It is discussed how this can be used in Mokken's (A theory
      and procedure of scale-analysis, Mouton, The Hague, 1971) scale analysis. 

PMID- 24659374
TI  - Trastuzumab emtansine: a review of its use in patients with HER2-positive
      advanced breast cancer previously treated with trastuzumab-based therapy.
AB  - Trastuzumab emtansine (KadcylaTM) is an antibody-drug conjugate consisting of the
      humanized anti-human epidermal growth factor receptor (HER) 2 antibody
      trastuzumab covalently linked to the highly potent microtubule inhibitory drug
      DM1 (a cytotoxic derivative of maytansine) via a stable thioether linker.
      Intravenous trastuzumab emtansine was recently approved for use in patients with
      HER2-positive, unresectable, locally advanced (in the EU) or metastatic (in the
      USA and EU) breast cancer who had previously received trastuzumab and a taxane
      (separately or in combination), making it the first antibody-drug conjugate
      approved in this indication. This article reviews the efficacy and tolerability
      of trastuzumab emtansine in these patients and summarizes its pharmacology. In
      the well-designed EMILIA study, trastuzumab emtansine significantly prolonged
      progression-free survival and overall survival, relative to treatment with
      lapatinib plus capecitabine, in patients with HER2-positive, unresectable,
      locally advanced or metastatic breast cancer who were previously treated with
      trastuzumab and a taxane. Trastuzumab emtansine was generally well tolerated in
      this study, with <6% of patients discontinuing treatment because of adverse
      events. Based on its efficacy and favourable tolerability, the US National
      Comprehensive Cancer Network guidelines recommend trastuzumab emtansine as the
      preferred option in patients with HER2-positive metastatic breast cancer who have
      received previous trastuzumab-based therapy.

PMID- 24659375
TI  - Meta-review: adverse effects of inhaled corticosteroids relevant to older
      patients.
AB  - BACKGROUND: In recent years, clinical trials and observational studies have
      raised concerns about the potential adverse effects of inhaled corticosteroids
      (ICS) such as pneumonia, cataract, fractures and hyperglycaemia, which are of
      particular concern for older patients. METHODS: We conducted a meta-review by
      searching electronic databases (MEDLINE, EMBASE, PubMed) for systematic reviews
      and meta-analyses of ICS use and the adverse effects of interest. We also
      evaluated new primary studies that reported information beyond that available
      from previously published meta-analyses. Two reviewers independently extracted
      data on measures of associated harm with ICS use. RESULTS: We identified five
      relevant meta-analyses for inclusion in this meta-review, and also three new
      studies of ICS and pneumonia. We found consistent evidence of a dose-response
      relationship between ICS use and serious adverse effects such as fractures and
      pneumonia. The estimated number needed to treat for harm due to fracture with ICS
      was 83 with 3-years use, and 60 per year for pneumonia. Both asthma and chronic
      obstructive pulmonary disease (COPD) users of ICS were at risk of pneumonia, with
      fluticasone appearing to confer higher risk than budesonide. There is also some
      suggestion that ICS use is associated with cataracts in a dose-response manner
      but the evidence is less robust here. Equally, the influence of ICS on diabetes
      mellitus remains uncertain. CONCLUSIONS: In view of the dose-response
      relationship seen between ICS use and important adverse effects such as fractures
      and pneumonia, clinicians needs to carefully balance the benefits of ICS versus
      the harms in older patients receiving long-term high-dose ICS.

PMID- 24659376
TI  - Functional gels based on chemically modified graphenes.
AB  - Chemically modified graphene (CMG) materials have been extensively studied
      because of their unique structures, excellent properties, and potential
      applications in energy storage and conversion, catalysis, and environment
      remediation. However, the unique two-dimensional structure and amphiphilicity
      make CMG sheets easily restack into irregular aggregates, which greatly reduces
      their accessible surface area, and thereby deteriorates their performance in
      practical applications. To exploit their inherent properties fully, CMGs usually
      have to be fabricated or assembled into functional gels with desired three
      dimensional (3D) interconnected porous microstructures. In this review, we
      summarize the recent achievements in the synthesis of CMG-based functional gels,
      including hydrogels, organogels, aerogels, and their composites. The mechanisms
      of gel formation and the applications of these functional gels will also be
      discussed. 

PMID- 24659377
TI  - Enhanced expression of IMPDH2 promotes metastasis and advanced tumor progression
      in patients with prostate cancer.
AB  - PURPOSE: Our previous study showed the upregulation of inosine 5'-monophosphate
      dehydrogenase type II (IMPDH2) protein in human prostate cancer (PCa) tissues and
      sera compared to non-cancerous controls by proteomics and ELISA analyses.
      However, the clinical significance of IMPDH2 in PCa has not been fully
      elucidated. Thus, the aim of the current study was to investigate the
      associations of IMPDH2 upregulation with tumor progression in patients with PCa.
      METHODS: IMPDH2 expression at mRNA and protein levels in human PCa and non
      cancerous prostate tissues was respectively detected by qRT-PCR, Western blot and
      immunohistochemistry analyses, which was validated by microarray-based Taylor
      Data. Then, the association of IMPDH2 expression with clinicopathological
      features of PCa patients was statistically analyzed. RESULTS: Compared with non
      cancerous prostate tissues, IMPDH2 mRNA and protein expression levels were both
      significantly upregulated (at mRNA level: 9.22 +/- 2.49 vs 5.06 +/- 1.45, P <
      0.01; at protein level by Western blot: 0.674 +/- 0.029 vs 0.418 +/- 0.140, P <
      0.001; at protein level by immunohistochemistry: 4.97 +/- 0.760 vs 3.32 +/- 1.66,
      P < 0.001) in PCa tissues, which were consistent with our previous data. In
      addition, the enhanced expression of IMPDH2 in PCa tissues was significantly
      correlated with the advanced clinical stage (for our cohort: P < 0.001; for
      Taylor data: P = 0.002), the presence of metastasis (for our cohort: P < 0.001;
      for Taylor data: P = 0.012) and the higher Gleason score (for our cohort: P =
      0.002; for Taylor data: P = 0.028). CONCLUSIONS: These findings suggest for the
      first time that the enhanced expression of IMPDH2 may promote the tumor
      metastasis and the advanced tumor progression in patients with PCa.

PMID- 24659378
TI  - Cluster of influenza A cases in vaccinated population of adults in Virology
      Laboratory in Glasgow in December 2012.
AB  - BACKGROUND AND AIMS: The majority of influenza infections during the 2012/2013
      influenza season in Scotland have been due to influenza A H3N2. We report an
      outbreak of influenza A H3N2 in a vaccinated population of adults in the Regional
      Virology Laboratory in Glasgow. This investigation was carried out to confirm the
      epidemiological link between cases. METHODS AND RESULTS: Staff with clinical
      symptoms of influenza-like illness were included. Samples were tested by real
      time polymerase chain reaction and sequencing. Staff were interviewed to obtain
      information regarding symptom onset and vaccination status. Eight confirmed cases
      and six clinically diagnosed cases were reported, which all occurred within 4
      days of a lunchtime Christmas quiz. The eight samples subtyped as H3 virus. The
      haemagglutinin gene in the confirmed cases was sequenced and shown to be
      identical. Most of the attendees had been immunised against influenza with the
      same vaccine batch at least 6 weeks earlier. CONCLUSION: This outbreak appears to
      have been an isolated incident, which arose due to a social event that provided
      the ideal conditions for transmission of a respiratory disease. It may have been
      compounded by low-vaccine effectiveness this season. Sequence data supported the
      epidemiological link.

PMID- 24659379
TI  - Are internet sites providing evidence-based information for patients suffering
      with Trigeminal Neuralgia?
AB  - Trigeminal neuralgia has a variety of treatments with variable efficacy.
      Sufferers present to a spectrum of disciplines. While traditional delivery of
      medical information has been by oral/printed communication, up to 50-80% patients
      access the internet for information. Confusion, therefore, may arise when seeking
      treatment for trigeminal neuralgia. We evaluated the quality of information on
      the internet for trigeminal neuralgia using the DISCERN(c) instrument. Only 54%
      websites had clear objectives; 42% delivered on these. A total of 71% provided
      relevant information on trigeminal neuralgia, 54% being biased/unbalanced; 71%
      not providing clear sources of information. No website detailed the side-effect
      profile of treatments; 79% did not inform patients of the consequences/natural
      history if no treatment was undertaken; it was unclear if patients could
      anticipate symptoms settling or when treatment would be indicated. Internet
      information on trigeminal neuralgia is of variable quality; 83% of sites assessed
      were of low-to-moderate quality, 29% having 'serious shortcomings.' Only two
      sites scored highly, only one being in the top 10 search results. Websites on
      trigeminal neuralgia need to appreciate areas highlighted in the DISCERN(c)
      instrument, in order to provide balanced, reliable, evidence-based information.
      To advise patients who may be misguided from such sources, neurosurgeons should
      be aware of the quality of information on the internet. 

PMID- 24659380
TI  - The accuracy of colonoscopic localisation of colorectal tumours: a prospective,
      multi-centred observational study.
AB  - BACKGROUND AND AIMS: Colonoscopy is essential for accurate pre-operative
      colorectal tumour localisation, but its accuracy for localisation remains
      undetermined due to limitations of previous work. This study aimed to establish
      the accuracy of colonoscopic localisation and to determine how frequently
      inaccuracy results in altered surgical management. METHOD: A prospective, multi
      centred, powered observational study recruited 79 patients with colorectal
      tumours that underwent curative surgical resection. Patient and colonoscopic
      factors were recorded. Pre-operative colonoscopic and radiological lesion
      localisations were compared to intra-operative localisation using pre-defined
      anatomical bowel segments to determine accuracy, with changes in planned surgical
      management documented. RESULTS: Colonoscopy accurately located the colorectal
      tumour in 64/79 patients (81%). Five out of 15 inaccurately located patients
      required on-table alteration in planned surgical management. Pre-operative
      imaging was unable to visualise the primary tumour in 23.1% of cases, a finding
      that was more prevalent amongst bowel screener patients compared to symptomatic
      patients (45.8% vs. 13%; p = 0.003). CONCLUSION: Colonoscopic lesion localisation
      is inaccurate in 19.0% of cases and occurred throughout the colon with a change
      in on-table surgical management in 6.3%. With CT unable to visualise lesions in
      just under a quarter of cases, particularly in the screening population,
      preoperative localisation is heavily reliant on colonoscopy.

PMID- 24659381
TI  - Quantification of ultra-trace amounts of copper by using  off-line solid phase
      extraction-flame atomic absorption  spectrometric determination through the
      octadecyl  silica-bonded phase membrane (OSPM) C18 disks  impregnated with 2,2'
      [ethane-1,2-diylbis(thio)]dianiline.
AB  - This study reports a very selective, easy, and precise method for rapid
      separation of trace amounts of copper in aqueous samples using octadecyl silica
      bonded phase membrane disks modified by 2,2'-[ethane-1,2-diylbis(thio)]dianiline
      (EDTD) combined with flame atomic absorption spectrometric determination. In
      addition, the synthesis and spectral characterization of EDTD have been described
      in detail. All the affecting experimental variables such as pH, amount of
      modifier, eluent type, sample and eluent flow rate, interfering ions, and disk
      capacity were also investigated. The target analyte (trace copper) was
      quantitatively retained at pH = 4 and eluted with 6.0 mL of 0.5 M HNO3 at flow
      rates of 40 and 10 mL min-1 for analyte passage and elution steps, respectively,
      through the disks modified with 17.0 mg of EDTD. The proposed method also allows
      an enrichment factor of about 500 and has a detection limit of 0.005 ng mL-1. The
      method has been successfully applied for isolation and determination of copper in
      different water samples, peppers, and standard alloys.

PMID- 24659382
TI  - Biosurfactant-producing strains in enhancing solubilization and biodegradation of
      petroleum hydrocarbons in groundwater.
AB  - Three biosurfactant-producing strains designated as BS-1, BS-3, and BS-4 were
      screened out from crude oil-contaminated soil using a combination of surface
      tension measurement and oil spreading method. Thin layer chromatography and
      infrared analysis indicated that the biosurfactants produced by the three strains
      were lipopeptide, glycolipid, and phospholipid. The enhancement of solubilization
      and biodegradation of petroleum hydrocarbons in groundwater employing
      biosurfactant-producing strains was investigated. The three strain mixtures led
      to more solubilization of petroleum hydrocarbons in groundwater, and the
      solubilization rate was 10.5 mg l-1. The combination of biosurfactant-producing
      strains and petroleum-degrading strains exhibited a higher biodegradation
      efficiency of 85.4 % than the petroleum-degrading strains (71.2 %).
      Biodegradation was enhanced the greatest with biosurfactant-producing strains and
      petroleum-degrading strains in a ratio of 1:1. Fluorescence microscopy images
      illustrate that the oil dispersed into smaller droplets and emulsified in the
      presence of biosurfactant-producing strains, which attached to the oil. Thus, the
      biodegradation of petroleum hydrocarbons in groundwater was enhanced.

PMID- 24659383
TI  - Genomic counseling in the newborn period: experiences and views of genetic
      counselors.
AB  - As newborn screening (NBS) technology expands, genetic counselors will become
      more involved in counseling for NBS results, including those potentially
      generated from whole exome sequencing (WES) and eventually whole genome
      sequencing (WGS). Members of the National Society of Genetic Counselors (NSGC)
      responded to an online survey (n=208) regarding genomic counseling in the context
      of NBS. The majority of participants (82.1 %) did not feel prepared to counsel
      for WGS results from NBS. Counselors with previous WES/WGS counseling experience
      felt more prepared (p= 0.005) to counsel for WGS results from NBS than those
      without WES/WGS experience. Overall, counselors expressed ethical and practical
      concerns regarding WGS in NBS, as well as a need for additional training
      regarding this application of the technology before it is implemented. Based on
      the results of this study, genetic counselors voice caution to the larger
      genetics community regarding expansion of NBS to incorporate genomic sequencing
      and advocate for additional education prior to initiating WGS into NBS.

PMID- 24659384
TI  - Assault by battery: battery-related injury in the head and neck.
AB  - OBJECTIVES/HYPOTHESIS: To estimate nationwide incidence of emergency department
      (ED) visits for battery-related injury (BRI) occurring in the head and neck, and
      analyze demographic and anatomic-specific trends. METHODS: The National
      Electronic Injury Surveillance System (NEISS) was searched for BRI in the head
      and neck, with analysis for incidence, anatomic site, age and gender, and
      specific diagnoses. RESULTS: There were an estimated 18,803 head and neck BRI ED
      visits from 2003 to 2012. A total of 65.8% of patients were male. A total of
      92.8% of patients were treated/examined and then released, and 4.7% of patients
      were admitted. A plurality (34.2%) of patients had BRI related to nose injures,
      and this represented the youngest cohort (median: 3 years old). The vast majority
      of ear and nose diagnoses were "foreign bodies"; two-thirds of mouth injuries
      were related to burns, whereas lacerations predominated in the face and head.
      Nearly half of ED visits involved patients between 2 and 5 years of age. A total
      of 45.2% of cases involving patients >= 65 years of age were related to hearing
      aid batteries as foreign bodies. CONCLUSION: BRI in the head and neck results in
      a significant amount of ED visits. Mechanisms of injury vary by age and anatomic
      location, but a considerable male predilection exists. Whereas pediatric patients
      are primarily affected, particularly patients between 2 to 5 years of age,
      injuries do occur among adults. Importantly, the prevalence of dislodged hearing
      aid batteries in the elderly necessitates comprehensive patient education to
      increase awareness and counseling regarding this complication. Awareness of
      demographic and anatomic-specific trends reported in this analysis may be an
      invaluable adjunct for history-taking and clinical examination.

PMID- 24659385
TI  - Reversible symmetrical external capsule hyperintensity as an early finding of
      autoimmune encephalitis.

PMID- 24659386
TI  - Determination of plant growth regulators in pears by microwave-assisted
      extraction and liquid chromatography with electrospray ionization mass
      spectrometry.
AB  - A new method for the determination of six plant growth regulators, 3
      indolylacetic acid, 3-indolepropionic acid, 2-naphthoxyacetic acid, 2,4
      dicholrophenoxyacetic acid, 1-naphthlcetic acid, and methyl naphthalene-1
      acetate, in pears was established by liquid chromatography with electrospray
      ionization mass spectrometry. In this study, a microwave-assisted extraction
      technique was first applied for the determination of plant growth regulators in
      fruit and three cleanup techniques were, respectively, investigated for the
      purification of pear samples. The chromatographic separation was performed on a
      Diamonsil C18 column by using 0.01 mol/L formic acid/ammonium formate buffer
      solution (pH 3.5)/methanol (35:65, v/v) as the mobile phase with a flow rate of
      0.7 mL/min in 1:1 split mode. The LODs ranged from 0.3 to 1.9 MUg/kg. Under
      optimized conditions, the average recoveries (five replicates) for six plant
      growth regulators (spiked at 0.01, 0.05, and 0.5 mg/kg) ranged from 78.9 to
      118.0%, and the RSDs were 1.4-10.3%. 

PMID- 24659387
TI  - A new unconventional HLA-A2-restricted epitope from HBV core protein elicits
      antiviral cytotoxic T lymphocytes.
AB  - Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus
      (HBV) infection and viral clearance. However, most of identified CTL epitopes are
      derived from HBV of genotypes A and D, and few have been defined in virus of
      genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is
      the most conservative and immunogenic component, in this study we used an
      overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL
      epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered
      and structurally characterized by crystallization analysis. The immunogenicity
      and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice.
      Finally, we show that mutations in HBc141-149 epitope are associated with viral
      parameters and disease progression in HBV infected patients. Our data therefore
      provide insights into the structure characteristics of this unconventional
      epitope binding to MHC-I molecules, as well as epitope specific CTL activity that
      orchestrate T cell response and immune evasion in HBV infected patients.

PMID- 24659388
TI  - The outcome and survival of palliative surgery in thoraco-lumbar  spinal
      metastases: contemporary retrospective cohort study.
AB  - Purpose: To evaluate outcome and survival and to identify prognostic variables
      for patients surgically treated for spinal metastases. Methods: A retrospective
      study was performed on 86 patients, surgically treated for spinal metastases.
      Preoperative analyses of the ASIA and spinal instability neoplastic scores (SINS)
      were performed. Survival curves of different prognostic variables were made by
      Kaplan-Meier analysis and the variables entered in a Cox proportional hazards
      model to determine their significance on survival. The correlation between
      preoperative radiotherapy and postoperative wound infections was also evaluated.
      Results: Survival analysis was performed on 81 patients,37 women and 44 men. Five
      patients were excluded due to missing data. Median overall survival was 38 weeks
      [95 % confidence interval (CI) 27.5-48.5 weeks], with a 3-month survival rate of
      81.5 %. Breast tumor had the best median survival of 127 weeks and lung tumor the
      worst survival of 18 weeks. Univariate analysis showed tumor type, preoperative
      ASIA score (p = 0.01) and visceral metastases(p = 0.18) were significant
      prognostic variables for survival.Colon tumors had 5.53 times hazard ratio
      compared to patients with breast tumor. ASIA-C score had more than 13.03 times
      the hazard ratio compared to patients with an ASIA-E score. Retrospective
      analysis of the SINS scores showed 34 patients with a score of 13-18 points, 44
      patients with a score of 7-12 points, and 1 patient with a score of 6 points.
      Preoperative radiotherapy had no influence on the postoperative incidence of deep
      surgical wound infections (p = 0.37). CONCLUSIONS: Patients with spinal
      metastases had a median survival of 38 weeks postoperative. The primary tumor
      type and ASIA score were significant prognostic factors for survival.
      Preoperative radiotherapy neither had influence on survival nor did it constitute
      a risk for postoperative surgical wound infections.

PMID- 24659389
TI  - Serum titanium, niobium and aluminium levels two years  following instrumented
      spinal fusion in children: does implant  surface area predict serum metal ion
      levels?
AB  - PURPOSE: Measurement of serum metal ion levels is used to determine systemic
      exposure to implant-derived metal debris that may be generated by processes of
      wear and corrosion. The aim of this study is to investigate predictors of serum
      metal ion levels in children undergoing instrumented spinal arthrodesis using a
      titanium alloy, focusing on implant characteristics and instrumentation construct
      design variables. METHODS: This prospective longitudinal cohort study involved 33
      children. Serum samples were obtained preoperatively:and at five defined interval
      periods over the first:two post-operative years. Samples were analysed using high
      resolution:inductively coupled plasma mass spectrometry to measure titanium,
      niobium and aluminium concentrations. Instrumentation characteristics were
      catalogued and construct surface area (SA) measurements calculated using an
      implant-specific software algorithm tool. RESULTS: Significantly elevated levels
      of serum titanium and niobium were observed (p< 0.0001), with >95 % of post
      operative levels abnormally elevated. Significant predictors of serum titanium
      and niobium levels included time since surgery, surgical procedure (posterior or
      anterior fusion), number of levels fused, number of pedicle screws inserted,
      total rod length, total metal SA, total exposed metal SA and total metal-on-metal
      SA. All significant instrumentation variables were highly correlated.
      CONCLUSIONS: There is a strong relationship between implant SA and both serum
      titanium and niobium levels. The direct clinical implications of these findings
      for patients are uncertain, but remain of concern. Surgeons should be aware of
      the strong correlation between implant surface area of the chosen construct and
      the subsequent serum metal ion levels.

PMID- 24659391
TI  - Advancing community-based research with urban American Indian populations:
      multidisciplinary perspectives.
AB  - The US has witnessed significant growth among urban American Indian (AI)
      populations in recent decades, and concerns have been raised that these
      populations face equal or greater degrees of disadvantage than their reservation
      counterparts. Surprisingly little urban AI research or community work has been
      documented in the literature, and even less has been written about the influences
      of urban settings on community-based work with these populations. Given the deep
      commitments of community psychology to empowering disadvantaged groups and
      understanding the impact of contextual factors on the lives of individuals and
      groups, community psychologists are well suited to fill these gaps in the
      literature. Toward informing such efforts, this work offers multidisciplinary
      insights from distinct idiographic accounts of community-based behavioral health
      research with urban AI populations. Accounts are offered by three researchers and
      one urban AI community organization staff member, and particular attention is
      given to issues of community heterogeneity, geography, membership, and
      collaboration. Each first-person account provides "lessons learned" from the
      urban context in which the research occurred. Together, these accounts suggest
      several important areas of consideration in research with urban AIs, some of
      which also seem relevant to reservation-based work. Finally, the potential role
      of research as a tool of empowerment for urban AI populations is emphasized,
      suggesting future research attend to the intersections of identity, sense of
      community, and empowerment in urban AI populations.

PMID- 24659390
TI  - Does neighborhood social capital buffer the effects of maternal depression on
      adolescent behavior problems?
AB  - Neighborhood characteristics have been shown to impact child well-being. However,
      it remains unclear how these factors combine with family characteristics to
      influence child development. The current study helps develop that understanding
      by investigating how neighborhoods directly impact child and adolescent behavior
      problems as well as moderate the influence of family characteristics on behavior.
      Using multilevel linear models, we examined the relationship among neighborhood
      conditions (poverty and social capital) and maternal depression on child and
      adolescent behavior problems. The sample included 741 children, age 5-11, and 564
      adolescents, age 12-17. Outcomes were internalizing (e.g. anxious/depressed) and
      externalizing (e.g. aggressive/hyperactive) behavior problems. Neighborhood
      poverty and maternal depression were both positively associated with behavior
      problems for children and adolescents. However, while neighborhood social capital
      was not directly associated with behavior problems, the interaction of social
      capital and maternal depression was significantly related to behavior problems
      for adolescents. This interaction showed that living in neighborhoods with higher
      levels of social capital attenuated the relationship between maternal depression
      and adolescent behavior problems and confirmed the expectation that raising
      healthy well-adjusted children depends not only on the family, but also the
      context in which the family lives.

PMID- 24659394
TI  - Combination of Cl-IB-MECA with paclitaxel is a highly  effective cytotoxic
      therapy causing mTOR-dependent autophagy  and mitotic catastrophe on human
      melanoma cells.
AB  - PURPOSE: Metastatic melanoma is the deadliest form of skin cancer. It is highly
      resistant to conventional therapies,particularly to drugs that cause apoptosis as
      the main anticancer mechanism. Recently, induction of autophagic cell death is
      emerging as a novel therapeutic target for apoptotic-resistant cancers. We aimed
      to investigate the underlying mechanisms elicited by the cytotoxic combination of
      2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide(Cl-IB-MECA, a
      selective A(3) adenosine receptor agonist; 10 MUM) and paclitaxel (10 ng/mL) on
      human C32 and A375 melanoma cell lines. METHODS: Cytotoxicity was evaluated using
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction, neutral
      red uptake, and lactate dehydrogenase leakage assays, after 48-h incubation.
      Autophagosome and autolysosome formation was detected by fluorescence through
      monodansylcadaverine-staining and CellLight((r)) Lysosomes-RFP-labelling,
      respectively. Cell nuclei were visualized by Hoechst staining, while levels of
      p62 were determined by an ELISA kit. Levels of mammalian target of rapamycin
      (mTOR) and the alterations of microtubule networks were evaluated by
      immunofluorescence. RESULTS: We demonstrated, for the first time, that the
      combination of Cl-IB-MECA with paclitaxel significantly increases cytotoxicity,
      with apoptosis and autophagy the major mechanisms involved in cell death.
      Induction of autophagy, using clinically relevant doses,was confirmed by
      visualization of autophagosome and autolysosome formation, and downregulation of
      mTOR and p62 levels. Caspase-dependent and caspase-independent mitotic
      catastrophe evidencing micro- and multinucleation was also observed in cells
      exposed to our combination. CONCLUSIONS: The combination of Cl-IB-MECA and
      paclitaxel causes significant cytotoxicity on two melanoma cell lines through
      multiple mechanisms of cell death. This multifactorial hit makes this therapy
      very promising as it will help to avoid melanoma multiresistance to chemotherapy
      and therefore potentially improve its treatment.

PMID- 24659395
TI  - Developmental determinants and changing patterns of respiratory outcomes after
      preterm birth.

PMID- 24659397
TI  - Medication reconciliation: a prospective study in an internal medicine unit.
AB  - BACKGROUND: Medication reconciliation has proved its effectiveness at improving
      drug-prescription safety. This study was undertaken to assess the impact of an
      intervention aimed at decreasing the discrepancies between a patient's usual
      treatment(s) and medications prescribed at admission. METHODS: Our study was
      conducted from November 2010 to May 2011. Discrepancies between home medication(
      s) and drugs prescribed to every patient aged C65 years, transferred from the
      Emergency Department and hospitalized in the Internal Medicine Unit, were
      analyzed. RESULTS: During this 6-month period, 170 patients were prospectively
      included, with a total of 1,515 medicines reconciled. The unintentional
      discrepancy rate declined from 4.3 to 0.9 % after the intervention. The main
      sources of discrepancies concerned alimentary tract and metabolism (25.7 %),
      cardiovascular (24 %), and nervous system drugs (19.4 %). CONCLUSIONS: The
      results of this study demonstrated that acquisition of patients' medication
      history is often incomplete or incorrect. Pharmacists seem to be especially well
      suited to help medical teams rectify this situation. However, the cost
      effectiveness of this intervention needs further assessment.

PMID- 24659398
TI  - Pharmacologic options in the management of upper gastrointestinal bleeding: focus
      on the elderly.
AB  - Despite the major advances in the treatment of peptic ulcer disease, its
      complication in the elderly has increased. This is because of the increasing use
      of nonsteroidal anti-inflammatory drugs, and the high prevalence of Helicobacter
      pylori infection. The presentation of peptic ulcers in the elderly patients can
      be subtle, and late presentation with upper gastrointestinal bleeding of peptic
      ulcers is not uncommon in the elderly population. The aim of this article is to
      review the current treatment options for upper gastrointestinal bleeding, and to
      discuss the place of drug therapy in both the acute and ongoing management of
      individual patients. Its focus will be on the benefits and risks of each option
      in the elderly. There is significant evidence to suggest that anti-secretory
      medications are useful in the treatment of peptic ulcers and associated
      complications in the elderly. Although a large number of studies have reported
      potential adverse effects of proton pump inhibitors, this evidence comes from
      retrospective observational studies, and such reports should be regarded with
      caution, and randomized controlled studies are required to confirm or refute
      these results. Nonetheless, it will be important to practice the appropriate use
      of acid suppression therapy, and identify which patients will gain maximum
      benefit from proton pump inhibitor therapy.

PMID- 24659399
TI  - The relevance of pneumococcal serotypes.
AB  - Pneumococcal disease leads to considerable mortality, morbidity and healthcare
      cost worldwide, and disease rates are predicted to increase due to an aging
      population. There are over 90 different pneumococcal serotypes identified to
      date, each with unique capsular characteristics capable of eliciting serotype
      specific immunity in its host. Several recent studies have demonstrated important
      differences in invasiveness, disease severity, complications from disease and
      antibiotic resistance patterns that are specific to individual serotypes. This
      knowledge is particularly pertinent given the ongoing seroepidemiological changes
      worldwide, partly due to the introduction of pneumococcal conjugate vaccination
      to childhood immunization schedules. Further characterization of pneumococcal
      serotype-specific clinical features, and continued surveillance of serotypes in
      nasopharyngeal carriage and disease, will help guide treatment and prevention
      strategies in pneumococcal disease. 

PMID- 24659401
TI  - Cleaning painted surfaces: evaluation of leaching phenomenon induced by solvents
      applied for the removal of gel residues.
AB  - Cleaning is one of the most important, delicate, and at the same time
      controversial processes in the conservation treatment of paintings. Although a
      strict definition of cleaning would be the removal of dirt, grime, or other
      accretions (surface cleaning), in the conservation field, cleaning is used in the
      broader meaning to include thinning/removing altered or "unwanted layers" of
      materials without damaging or altering the physicochemical properties of the
      surfaces to be preserved. The cleaning of unvarnished paintings is one of the
      most critical issues that are currently discussed. Several studies exist
      regarding different cleaning tools, such as gels, soaps, enzymes, ionic liquids,
      and foams, as well as various dry methods and lasers, but only a few have been
      performed on the risk associated with the use of water and organic solvents for
      the cleaning treatments in relation to the original paint binder. The aim of the
      study is to verify analytically the behavior of water gelling agents during
      cleaning treatments and the interaction of the following elements: water or
      organic solvents applied for the removal of gel residues with the original lipid
      paint binder. For this purpose, the study was conducted on a fragment of canvas
      painting (sixteenth to seventeenth century) of Soprintendenza per i Beni Storici,
      Artistici ed Etnoantropologici del Friuli Venezia Giulia (Superintendence for the
      Historical, Artistic and Ethno-anthropological Heritage of Friuli Venezia
      Giulia), Udine by means of Fourier transform infrared spectroscopy, gas
      chromatography/mass spectrometry, and scanning electron microscopy.

PMID- 24659400
TI  - Long-term disruption of growth, reproduction, and behavior after embryonic
      exposure of zebrafish to PAH-spiked sediment.
AB  - A natural sediment spiked with three individual polycyclic aromatic hydrocarbons
      (PAHs; pyrene, phenanthrene and benzo[a]pyrene) was used to expose zebrafish
      embryos and larvae during 4 days. The total PAH concentration was 4.4 MUg g(-1)
      which is in the range found in sediment from contaminated areas. Quantification
      of metabolites in the larvae after exposure confirmed the actual contamination of
      the larvae and indicated an active metabolism especially for pyrene and
      benzo[a]pyrene. After a transfer in a clean medium, the larvae were reared to
      adulthood and evaluated for survival, growth, reproduction, and behavior.
      Measured endpoints revealed a late disruption of growth (appearing at 5 months)
      and a trend toward a lower reproductive ability. Adults of embryos exposed to
      sediment spiked with PAHs displayed lethargic and/or anxiety-like behaviors. This
      latter behavior was also identified in offspring at larval stage. All together,
      these effects could have detrimental consequences on fish performances and
      contribution to recruitment.

PMID- 24659402
TI  - Protective effect of Syzygium cumini against pesticide-induced cardiotoxicity.
AB  - Pesticide-induced toxicity is a serious issue which has resulted in plethora of
      diseases all over the world. The organophosphate pesticide malathion has caused
      many incidents of poisoning such as cardiac manifestations. The present study was
      designed to evaluate the effect of Syzygium cumini on malathion-induced
      cardiotoxicity. Dose optimization of malathion and polyphenols such as curcumin,
      (-)-epicatechin, gallic acid, butylated hydroxyl toluene, etc. was done by MTT
      cell proliferation assay. Nuclear deformities, ROS production, and integrity of
      extra cellular matrix components were analyzed by different techniques. S. cumini
      methanolic pulp extract (MPE), a naturally derived gallic acid-enriched
      antioxidant was taken to study its effect on malathion-induced toxicity. Nuclear
      deformities, ROS production, and integrity of extra cellular matrix components
      were also analyzed. Twenty micrograms per milliliter LD50 dose of malathion was
      found to cause stress-mediated responses in H9C2 cell line. Among all the
      polyphenols, gallic acid showed the most significant protection against stress.
      Gallic acid-enriched methanolic S. cumini pulp extract (MPE) showed 59.76 % +/-
      0.05, 81.61 % +/- 1.37, 73.33 % +/- 1.33, 77.19 % +/- 2.38 and 64.19 % +/- 1.43
      maximum inhibition for DPPH, ABTS, NO, H2O2 and superoxide ion, respectively, as
      compared to ethanolic pulp extract and aqueous pulp extract. Our study suggests
      that S. cumini MPE has the ability to protect against the malathion-mediated
      oxidative stress in cardiac myocytes.

PMID- 24659403
TI  - Chromium phytoextraction from tannery effluent-contaminated soil by Crotalaria
      juncea infested with Pseudomonas fluorescens.
AB  - The aim of present study was to remediate chromium (Cr)-contaminated soil by
      Crotalaria juncea in the presence of Pseudomonas fluorescens. Inoculation of P.
      fluorescens in pot soil grown with C. juncea significantly increased (~2-fold)
      the water-soluble (Ws) and exchangeable (Ex) Cr contents in contaminated soil
      under greenhouse condition. It also enhanced the chlorophyll content by 92 % and
      plant biomass by 99 % as compared to the uninoculated C. juncea plant. The
      analysis showed that root and shoot uptake of Cr in C. juncea inoculated by P.
      fluorescens was 3.08- and 2.82-fold, respectively. This research showed that the
      association of C. juncea and P. fluorescens could be a promising technology for
      increasing the soil Cr bioavailability and plant growth for successful
      phytoextraction of Cr from the contaminated soil.

PMID- 24659404
TI  - EROD activity and antioxidant defenses of sea bass (Dicentrarchus labrax) after
      an in vivo chronic hydrocarbon pollution followed by a post-exposure period.
AB  - Chronic concentrations of polycyclic aromatic hydrocarbons (PAHs) have been
      commonly detected in international estuaries ecosystems. Reliable indicators
      still need to be found in order to properly assess the impact of PAHs in fish.
      After an in vivo chronic exposure to hydrocarbons, the enzymatic activity of 7
      ethoxyresorufin O-deethylase (EROD) and the antioxidant defense system were
      assessed in sea bass, Dicentrarchus labrax. A total of 45 fish were exposed to
      the water-soluble fraction of Arabian crude oil, similar to a complex pollution
      by hydrocarbons chronically observed in situ, while 45 other control fish
      sustained the same experimental conditions in clean seawater. Fish samples were
      made after a 21-day exposure period and after a 15-day recovery period in clean
      fresh water. Throughout the experiment, liver EROD activity was significantly
      higher in contaminated fish than in control fish. In addition, nonenzymatic
      (total glutathione) and enzymatic (GPx, SOD, and CAT) antioxidant defense
      parameters measured in liver were not significantly different in fish.
      Furthermore, in gills, glutathione content had significantly increased while SOD
      activity had significantly decreased in contaminated fish compared to controls.
      On the other hand, CAT and GPx activities were not affected. Chronic exposure to
      PAHs disturbing the first step (SOD) and inhibiting the second step (GPx and CAT)
      could induce oxidative stress in tissues by the formation of oxygen radicals.
      After the postexposure period, there was no significant difference between
      control and contaminated fish in any of the antioxidant defense parameters
      measured in gills, attesting to the reversibility of the effects. 

PMID- 24659405
TI  - A semiparametric statistical approach for forecasting SO2 and NOx concentrations.
AB  - This study develops a new semiparametric statistical approach for urban air
      quality forecasting. Compared to conventional approaches, the semiparametric
      approach allows the model users to benefit from the positive aspects and
      alleviate the negative ones of parametric and nonparametric approaches. Two
      advantages of the approach lie in (1) the interpretation of the data set being
      easily decoded and used by the model and (2) its capability in dependence on
      prior assumption. To illustrate the performance of the proposed approach, three
      semiparametric regression models (i.e., linear-, quadratic-, and interactive
      based semiparametric regression) are applied to an air quality forecasting
      problem in the city of Xiamen, China, and satisfactory training and prediction
      performance are obtained. The three models are also compared to three parametric
      and two nonparametric regression models. The results indicate that the predictive
      accuracy of semiparametric regression models is higher than those obtained from
      the parametric and stepwise cluster analysis models. However, the proposed three
      semiparametric regression models could be much favored, since they can be
      achieved more easily and rapidly than the artificial neural network model.

PMID- 24659406
TI  - Characterizing the heavy metal-complexing potential of fluorescent water
      extractable organic matter from composted municipal solid wastes using
      fluorescence excitation-emission matrix spectra coupled with parallel factor
      analysis.
AB  - To investigate the effect of organic matter evolution on heavy metal sorption,
      fluorescence excitation-emission matrix (EEM) spectra combined with parallel
      factor (PARAFAC) analysis were employed to characterize the evolution and metal
      complexing potential of fluorescent water-extractable organic matter (WEOM) from
      composted municipal solid wastes (MSWs). The WEOMs examined comprised humic-,
      fulvic-, tryptophan-, and tyrosine-like substances. Composting treatment
      increased the content of humic- and fulvic-like matter, and changed the existence
      pattern of tryptophan- and tyrosine-like substances (i.e., the tryptophan- and
      tyrosine-like substances from uncomposted MSWs were mainly bound in protein-like
      matter, whereas those from composted MSWs were primarily bound in humic- and
      fulvic-like substances). Furthermore, composting treatment increased the polar
      functional group, aromaticity, and humification degree of the WEOMs, but
      decreased the aliphatic and hydroxyl group. These evolutions decreased the Cu(II)
      affinities of fulvic- and humic-like substances and the Pb(II) affinities and
      complexing capacities of fulvic-like substances, but increased the Cu(II)
      complexing capacities of fulvic- and humic-like substances. These results reveal
      that mature composts from the MSWs can be used for the remediation of Cu- and Pb
      contaminated soils in situ, whereas immature composts can enhance the metal
      transferability from soil to plant.

PMID- 24659407
TI  - Effect of Pseudomonas sp. HF-1 inoculum on construction of a bioaugmented system
      for tobacco wastewater treatment: analysis from quorum sensing.
AB  - To better construct a bioaugmented system for tobacco wastewater treatment,
      activated sludge was inoculated with different concentrations of the nicotine
      degrading bacterium Pseudomonas sp. HF-1. The results showed that inoculum
      concentrations of 0.55 +/- 0.01 and 1.10 +/- 0.03 mg/g (dry weight of strain HF
      1/dry weight of activated sludge) were best to ensure strain HF-1 survival and
      successful bioaugmentation. The release pattern of autoinducer (AI) for quorum
      sensing in the bioaugmented system was also investigated. During the period of HF
      1 inoculation, compared with failed bioaugmented systems, AI-2 was significantly
      increased in the successful systems, suggesting that AI-2-mediated bacterial
      communication played an important role in the colonization of HF-1. When
      inoculation of strain HF-1 was stopped, the amount of AI-2 decreased and leveled
      out in all systems. Notably, there was a greater than threefold increase of short
      chain AHLs in failed bioaugmented systems, but no increase in successful ones,
      implying that the fluctuation of short-chain AHLs could be an indicator of the
      failure of bioaugmentation. Thus, AI-2-mediated quorum sensing could be
      implemented to facilitate HF-1 colonization.

PMID- 24659408
TI  - Perinatal outcome after laser surgery for triplet gestations with feto-fetal
      transfusion syndrome.
AB  - OBJECTIVE: The objective of this study is to evaluate the outcomes of fetoscopic
      laser photocoagulation (FLP) for a triplet gestation with feto-fetal transfusion
      syndrome (FFTS). METHOD: On the basis of chorionicity, perinatal outcome at 28
      days in triplets with FFTS after FLP were evaluated. RESULTS: Fetoscopic laser
      photocoagulation was completed for all 16 cases including nine dichorionic
      triamniotic (DT) cases and seven monochorionic triamniotic (MT) cases. The
      placenta was located anteriorly in six cases. The median gestational age at
      surgery was 21 (16-25) weeks, and the median operation time was 51 (25-125)
      minutes. Several technical maneuvers to complete the procedure in MT, such as
      trocar assistance in two cases, intentional septostomy of the dividing membrane
      in one, and double uterine entry in one, were used. The median gestational age at
      delivery was 31 (23-34) weeks. Overall perinatal survival in DT was 74% and that
      of MT was 95%. All 16 cases resulted in at least one survival, whereas three
      neonates survived in 44% of DT cases and in 86% of MT cases. Two MT neonates
      suffered severe intraventricular hemorrhages. CONCLUSIONS: Fetoscopic laser
      photocoagulation for FFTS in MT as well as DT triplets seems a valuable
      treatment.

PMID- 24659409
TI  - Perioperative Management of DORV.
AB  - The diagnosis of double-outlet right ventricle (DORV) characterizes a complex
      heterogeneous group of congenital cardiac malformations for which multiple
      classification schemes have been used. A clear understanding of the anatomy is
      critical to understanding the physiologic consequences of the specific type of
      DORV. Perioperative considerations include the medical management of the patient
      during the preoperative period, anesthetic and surgical management, and
      postoperative care. Both anesthetic and surgical management strategies are very
      different depending on the type of DORV. Key principles for anesthetic management
      include balancing the systemic and pulmonary circulations, optimizing systemic
      cardiac output, and closely monitoring for impaired oxygen delivery to the
      tissues. Depending on the specific anatomy the patient is usually placed on a 1-
      or 2-ventricle pathway, and initial palliation may involve placement of a
      systemic arterial to pulmonary artery shunt or pulmonary artery banding. In some
      cases the child may undergo a complete repair during the first few months of
      life. Surgical outcomes, both short and long-term, are dependent on the type of
      DORV and surgical procedure done. These patients require long-term follow up and
      may present for surgical or catheter-based interventions as adults. 

PMID- 24659410
TI  - Is neutrophil lymphocyte ratio an indicator for proteinuria in chronic kidney
      disease?
AB  - BACKGROUND: Recent studies have shown that neutrophil lymphocyte ratio (NLR) is a
      strong indicator in determining inflammation in cardiac and non-cardiac diseases.
      We aimed to evaluate the relationship between proteinuria and NLR in chronic
      kidney disease (CKD) patients without diabetes mellitus (DM). METHODS: Between
      2011 and 2012 files of a total of 1000 CKD patients attending outpatient clinic
      were retrospectively scanned. Patients with DM, chronic disease, malignancy or
      stage 5 CKD were excluded. After these patients were excluded, a total of 69
      patients with stage 3 and 4 CKD were evaluated. RESULTS: The study comprised 27
      patients with CKD without proteinuria (Group 1), 42 patients with CKD and
      proteinuria (Group 2) and 30 healthy volunteers (Group 3). NLR was highest in
      Group 2 and this was statistically significant compared with the control group (p
      = 0.012). The platelet lymphocyte ratio (PLR) in Group 2 was higher than the
      control group at a significant level (p = 0.004). There was a moderate positive
      correlation found between proteinuria and NLR (p = 0.013, r = 0.3). There was a
      positive correlation found between proteinuria and PLR (p = 0.002, r = 0.306).
      CONCLUSION: In conclusion, NLR, a parameter easily found in routine blood counts
      of CKD patients, is a marker with prognostic value for the presence and degree of
      proteinuria.

PMID- 24659411
TI  - Vaccination Related Pain: Comparison of Two Injection Techniques.
AB  - OBJECTIVE: To compare the acute pain response during immunization in infants
      using a slow "standard" injection technique vs. "pragmatic" technique. METHODS:
      In this randomised controlled trial, source of data were 200 healthy infants of
      age group 6 wk to one and half years, receiving routine intramuscular
      vaccination. They were divided randomly using computer generated random numbers
      into 'Standard group' receiving immunization using standard slow technique with
      aspiration and 'Pragmatic group' receiving immunization using "pragmatic"
      technique without aspiration. The entire vaccination procedure was videotaped.
      Videos were scored for pain using modified behavioral pain scale (MBPS) by 2
      clinical psychologists and the mean score was considered for analysis. Pain was
      scored within 15 s of the immunization, were measured and described the child's
      maximal pain response to the injection. Cry time was measured by a different
      person from the start of cry till it ends. Entire data was entered in a preformed
      proforma. The Z test for two sample population means was used for statistical
      analysis. RESULTS: Standard technique of vaccination needs longer time to
      administer (5-10 s) when compared to pragmatic technique (1-2 s). Mean post
      vaccination MBPS in standard group was 8.4 (SD - 0.75) and in pragmatic group was
      7.8 (SD - 1.17) which was statistically significant (p - 0.00). Mean crying
      duration in pragmatic group was less (32.1 s) than standard group (37.37 s).
      CONCLUSIONS: The "standard" slow technique was significantly more painful and
      took longer to administer than the "pragmatic" rapid technique. Cry duration is
      lesser in pragmaticgroup than standard group, but it is statistically not
      significant.

PMID- 24659412
TI  - Low postprandial circulating inactive ghrelin: role of early satiety in
      undernourished children.
AB  - OBJECTIVE: To determine difference in the levels of circulating inactive ghrelin
      between undernourished and healthy children. METHODS: The present cross-sectional
      study was conducted in undernourished children from southwestern Iran, from July
      2011 through July 2012. Postprandial inactive ghrelin levels were measured in 40
      undernourished children and sex- and age-matched healthy controls by enzyme
      immunoassay. RESULTS: The levels of postprandial inactive ghrelin were
      considerably lower in undernourished compared to the healthy children (6.4 vs.
      12.9, P < 0.001). Among the undernourished children, the level of inactive
      ghrelin was significantly lower in girls than in boys (5.8 vs. 7.1, P = 0.032).
      CONCLUSIONS: Thus, the levels of inactive ghrelin was found to be low in
      undernourished children compared to healthy children. Early loss of appetite
      might be a result of low circulating inactive ghrelin levels in the postprandial
      state in undernourished children.

PMID- 24659413
TI  - The BIANCA model/code of radiation-induced cell death: application to human cells
      exposed to different radiation types.
AB  - This paper presents a biophysical model of radiation-induced cell death,
      implemented as a Monte Carlo code called BIophysical ANalysis of Cell death and
      chromosome Aberrations (BIANCA), based on the assumption that some chromosome
      aberrations (dicentrics, rings, and large deletions, called ''lethal
      aberrations'') lead to clonogenic inactivation. In turn, chromosome aberrations
      are assumed to derive from clustered, and thus severe, DNA lesions (called
      ''cluster lesions,'' or CL) interacting at the micrometer scale; the CL yield and
      the threshold distance governing CL interaction are the only model parameters.
      After a pilot study on V79 hamster cells exposed to protons and carbon ions, in
      the present work the model was extended and applied to AG1522 human cells exposed
      to photons, He ions, and heavier ions including carbon and neon. The agreement
      with experimental survival data taken from the literature supported the
      assumptions. In particular, the inactivation of AG1522 cells was explained by
      lethal aberrations not only for X-rays, as already reported by others, but also
      for the aforementioned radiation types. Furthermore, the results are consistent
      with the hypothesis that the critical initial lesions leading to cell death are
      DNA cluster lesions having yields in the order of *2 CL Gy-1 cell-1 at low LET
      and*20 CL Gy-1 cell-1 at high LET, and that the processing of these lesions is
      modulated by proximity effects at the micrometer scale related to interphase
      chromatin organization. The model was then applied to calculate the fraction of
      inactivated cells, as well as the yields of lethal aberrations and cluster
      lesions, as a function of LET; the results showed a maximum around 130 keV/lm,
      and such maximum was much higher for cluster lesions and lethal aberrations than
      for cell inactivation.

PMID- 24659414
TI  - Adaptable hetero Diels-Alder networks for fast self-healing under mild
      conditions.
AB  - A novel adaptable network based on the reversible hetero Diels-Alder reaction of
      a cyanodithioester and cyclopentadiene is presented. Reversible between 50-120 
      degrees C, the adjustable and self-healing features of the network are evidenced
      via temperature dependent rheology experiments and repetitive tensile tests
      whereas the network's chemical structure is explored by temperature dependent (1)
      H MAS-NMR spectroscopy. 

PMID- 24659415
TI  - Depression, stress, and intimate partner violence among Latino migrant and
      seasonal farmworkers in rural Southeastern North Carolina.
AB  - The purpose of the study is to identify the predictors of depression and intimate
      partner violence (IPV) among Latinos in rural Southeastern North Carolina. A
      sample of 291 migrant and seasonal farmworkers was interviewed to complete the
      demographic questionnaire, HITS (intimate violence tendency), Migrant Farmworker
      Stress Inventory, Center for Epidemiologic Studies Depression Scale (depression),
      and CAGE/4M (alcohol abuse). OLS regression and structural equation modeling were
      used to test the hypothesized relations between predictors of IPV and depression.
      The findings indicated that respondents reporting higher levels of stress also
      reported higher levels of IPV and depression. The goodness-of-fit statistics for
      the overall model again indicated a moderate fit of the model to the data (chi2 =
      5,612, p < .001; root mean square error for approximation = 0.09; adjusted
      goodness-of-fit index = 0.44; comparative fit index = 0.52). Although the
      findings were not robust to estimation in the structural equation models, the OLS
      regression models indicated direct associations between IPV and depression.

PMID- 24659416
TI  - Chlorophyll and suspended sediment mapping  to the Caribbean Sea from rivers in
      the capital city  of the Dominican Republic using ALOS AVNIR-2 data.
AB  - This study aims to study the distribution of contaminants in rivers that flow
      into the Caribbean Sea using chlorophyll-a (Chl-a) and suspended sediment (SS) as
      markers and ALOS AVNIR-2 satellite sensor data. The Haina River (HN) and Ozama
      and Isabela Rivers (OZ-IS) that flow through the city of Santo Domingo, the
      capital of the Dominican Republic, were chosen. First, in situ spectral
      reflectance/Chl-a and SS datasets obtained from these rivers were acquired in
      March 2011 (case A: with no rain influence) and June 2011 (case B: with rain
      influence), and the estimation algorithm of Chl-a and SS using AVNIR-2 data was
      developed from the datasets. Moreover, the developed algorithm was applied to
      AVNIR-2 data in November 2010 for case A and August 2010 for case B. Results
      revealed that for Chl-a and SS estimations under cases A and B conditions, the
      reflectance ratio of AVNIR-2 band 4 and band 3 (AV4/AV3) and the reflectance of
      AVNIR-2 band 4 (AV4) were effective. The Chl-a and SS mapping results obtained
      using AVNIR-2 data corresponded with the field survey results. Finally, an
      outline of the distribution of contaminants at the mouth of the river that flows
      into the Caribbean Sea was obtained for both rivers in cases A and B.

PMID- 24659417
TI  - Cdk5 inhibitor roscovitine alleviates neuropathic pain in the dorsal root ganglia
      by downregulating N-methyl-D-aspartate receptor subunit 2A.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a member of the small proline-directed
      serine/threonine kinase family. Cdk5 is not involved in cell cycle regulation,
      but is implicated in neurodegenerative disorders. However, the role of Cdk5 in
      neuropathic pain remains unclear. This study aimed to evaluate the possibility
      that Cdk5 is involved in neuropathic pain in the dorsal root ganglia (DRG). We
      injected intrathecally Cdk5 inhibitor roscovitine in rat model of chronic
      compression of dorsal root ganglion and examined pain behaviors and the
      expression of N-methyl-d-aspartate receptor subunit 2A (NR2A) but not NR2B or NR1
      in DRG. We found that roscovitine alleviated neuropathic pain, causing decline in
      paw withdrawal mechanical threshold and paw withdrawal thermal latency.
      Furthermore, roscovitine inhibited NR2A expression in DRG. These data suggest
      that Cdk5-NR2A pathway regulates neuropathic pain in DRG, and intrathecal
      injection of roscovitine could alleviate neuropathic pain. Our findings provide
      new insight into the analgesic effects of Roscovitine and identify Cdk5-NR2A
      pathway as a potential target for effective treatment of neuropathic pain.

PMID- 24659418
TI  - Subacute visual loss and bilateral fixed mydriasis: an atypical case of giant
      cell arteritis.

PMID- 24659419
TI  - Novel splice site mutation of SPG4 in a Chinese family with hereditary spastic
      paraplegia.

PMID- 24659420
TI  - Health improvement for men and hard-to-engage-men delivered in English Premier
      League football clubs.
AB  - Unhealthy behaviours represent modifiable causes of non-communicable disease. In
      men, concern focuses on those (i) demonstrating the poorest health, exacerbated
      by a lack of awareness of the risks that their lifestyles pose and (ii) who
      neither consult their doctor nor use health services. Classed as 'hard-to
      engage', distinctive strategies are needed to reach these men. Impact and process
      evaluations assessed the effect of a programme of men's health-delivered in/by
      English Premier League football clubs. Men attended match-day events and/or
      weekly classes involving physical activity and health education. Validated self
      report measures for demographics and lifestyle behaviours were completed pre- and
      post-intervention. Intention-to-treat analysis was performed on pre-versus-post
      intervention differences in lifestyle profiles, whereas interviews (n = 57)
      provided men's accounts of programme experience. Participants were predominantly
      white British (70.4%/n = 2669), 18-44 (80.2%/n = 3032) and employed (60.7%/n =
      1907). One-third (n = 860) 'never' visited their doctor. Over 85% (n = 1428)
      presented with combinations of lifestyle risk factors. Intention-to-treat
      analysis showed improvements (P < 0.001) in lifestyle profiles. Interviews
      confirmed recruitment of men who were hard-to-engage and unhealthy. Men were
      attracted through football and/or the clubs, whereas specific design factors
      impacted on participation. Limitations include use of self-reports, narrow
      demographics, small effect sizes, lack of follow-up and the absence of non
      completers in interviews. 

PMID- 24659421
TI  - The 3-year evolution of a preschool physical activity intervention through a
      collaborative partnership between research interventionists and preschool
      teachers.
AB  - Despite evidence that preschoolers spend the majority of their time in sedentary
      activities, few physical activity interventions have focused on preschool-age
      children. Health promotion interventions that can be integrated into the daily
      routines of a school or other setting are more likely to be implemented. The
      Study of Health and Activity in Preschool Environments employed a flexible
      approach to increasing physical activity opportunities in preschools' daily
      schedules through recess, indoor physical activity and physical activity
      integrated into academic lessons. Eight preschools were randomly assigned to
      receive the study's physical activity intervention. Teachers in these schools
      partnered with university-based interventionists across 3 years to design and
      implement a flexible and adaptive intervention. The intervention approach
      included trainings and workshops, site visits and feedback from intervention
      personnel, newsletters, and physical activity equipment and materials. Teachers
      reported a high acceptability of the intervention. The purpose of this article is
      to describe the evolution of a multi-component physical activity intervention in
      preschools, including (i) a description of the intervention components, (ii) an
      explanation of the intervention process and approach, and (iii) a report of
      teachers' perceptions of barriers to implementation. 

PMID- 24659422
TI  - Quantitative analysis and pharmacokinetics study of tigecycline in human serum
      using a validated sensitive liquid chromatography with tandem mass spectrometry
      method.
AB  - Tigecycline, a novel intravenously administered glycylcycline antibiotic,
      currently plays a key role in the management of complicated multiorganism
      infections. However, current liquid chromatography with tandem mass spectrometry
      methods briefly describe parameters and the only reported internal standard was
      sometimes difficult to obtain. In our study, an updated liquid chromatography
      with tandem mass spectrometry method for the quantitative analysis of tigecycline
      in human serum was developed. Sample preparation involved precipitation with 20%
      trichloroacetic acid. Chromatographic separation of tigecycline and tetracycline
      (internal standard) was achieved on a Hypersil GOLD C18 column using gradient
      elution. The selected reaction monitoring transitions were performed at m/z 586.1
      >513.2 for tigecycline and m/z 445.1->410.2 for tetracycline. The assay was
      linear over the concentration range of 5-2000 ng/mL. The intra- and interday
      precisions at three concentration levels (10, 100, and 1600 ng/mL) were <15% and
      their accuracies were within the range of 95.1-106.1%. The mean recovery ranged
      from 94.3 to 105.6% and the matrix effect from 92.1 to 97.6%. Tigecycline was
      stable under all tested conditions. This validated method was successfully
      applied to a pharmacokinetic study in critically ill patients. The data
      demonstrated that our method allows quantification of tigecycline in serum in a
      quick and reliable manner for widespread application. 

PMID- 24659423
TI  - Changes in T lymphocyte subsets in mice with CT26 colon tumors after treatment
      with donor lymphocyte infusion.
AB  - The objective of this study was to detect changes in T lymphocyte subpopulations
      in mice with CT26 subcutaneous colon cancer after treatment with donor lymphocyte
      infusion (DLI) and cyclophosphamide (CP) chemotherapy. A colon cancer model was
      established by subcutaneous injection of CT26 carcinoma cells into BALB/C mice.
      The mice were randomized into different treatment groups. We recorded survival
      times, tumor growth inhibition rates, histopathological changes, and T lymphocyte
      subsets in peripheral blood of the mice. Mice treated with DLI and CP survived
      33.5 +/- 5.02 days, which was significantly longer than the survival time of
      untreated control mice (16.7 +/- 2.98 days, P < 0.01). In addition, the tumor
      inhibitory rate was higher in mice treated with DLI and CP (89.3 %) than that in
      mice treated with CP or DLI alone (67.1 and 34.5 %, respectively). There were
      higher levels of T lymphocytes that were CD3(+) and CD4(+) in mice treated with
      DLI alone or the combination of CP and DLI (P < 0.05), and the ratio of
      CD4(+)/CD8(+) cells was significantly improved in these mice (P < 0.05). DLI
      combined with chemotherapy significantly prolonged survival and inhibited tumor
      growth in mice with CT26 colon cancer. This treatment might also improve immune
      function in these mice. Donor spleen cells that include high numbers of
      allogeneic lymphocytes and a few stem cells could induce a graft-versus-tumor
      effect, leading to elimination of residual cancer cells. This indicates that it
      is potentially a feasible adoptive cellular immunotherapy strategy for the
      management of solid tumors.

PMID- 24659424
TI  - Esophageal cancer-selective expression of TRAIL mediated  by MREs of miR-143 and
      miR-122.
AB  - Esophageal cancer is one of the most common digestive system neoplasms and has a
      quite poor prognosis. TNF-related apoptosis-inducing ligand (TRAIL) induces the
      apoptosis in a wide range of cancer cells including esophageal cancers. However,
      TRAIL also activates apoptotic pathway in normal cells. To improve the
      specificity of TRAIL action, we employed the microRNA (miRNA) response elements
      (MREs) of miR-143 and miR-122 to restrict TRAIL expression mediated by an
      adenoviral vector (Ad-TRAIL-143-122) in esophageal cancer cells. The experiments
      showed that Ad-TRAIL-143-122 was able to highly express TRAIL in esophageal
      cancer cells, but not normal cells. The selective TRAIL expression also led to
      selective apoptosis in esophageal cancer cells. Ad-TRAIL-143-122 greatly reduced
      the viability of esophageal cancer cells without cytotoxicity to normal cells. In
      mice, Ad-TRAIL-143-122 suppressed the growth of esophageal cancer xenografts and
      protected liver from TRAIL-induced toxicity. In this study, we constructed a
      biologic vector that can express exogenous genes in a tumor-specific manner. This
      strategy can simultaneously treat cancer and prevent hepatoxicity and thus may be
      a promising way for esophageal cancer treatment.

PMID- 24659425
TI  - Promoter methylation of DAPK gene may contribute  to the pathogenesis of nonsmall
      cell lung cancer: a meta-analysis.
AB  - We performed a meta-analysis of cohort studies to determine whether promoter
      methylation of the death-associated protein kinase (DAPK) gene contributes to the
      pathogenesis of nonsmall cell lung cancer (NSCLC). A range of electronic
      databases were searched: MEDLINE (1966 ~ 2013), the Cochrane Library Database
      (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science
      (1945 ~ 2013), and the Chinese Biomedical Database (CBM; 1982 ~ 2013) without any
      language restrictions. Meta-analysis was conducted using the STATA 12.0 software.
      Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Our
      meta-analysis integrated results from 12 clinical cohort studies that met all
      inclusion criteria with a total of 1,027 NSCLC patients. We observed that the
      frequency of DAPK gene methylation in cancer tissues were significantly higher
      than that in the adjacent normal and benign tissues (cancer tissues vs. benign
      tissues: OR=8.50, 95 % CI=5.88 ~ 12.28, P<0.001; cancer tissues vs. adjacent
      tissues: OR=5.95, 95 % CI=4.11 ~ 8.60, P<0.001; cancer tissues vs. normal
      tissues: OR=4.75, 95 % CI=3.28 ~ 6.87, P<0.001; respectively). Subgroup analysis
      by ethnicity demonstrated that DAPK gene methylation was closely associated with
      the development and progression of NSCLC among both Asians and Caucasians (all
      P<0.05). Furthermore, we conducted a subgroup analysis based on sample source and
      discovered that DAPK gene methylation was implicated in the pathogenesis of NSCLC
      in both blood and tissue subgroups (all P<0.05). Our results suggest that DAPK
      promoter methylation may be involved in NSCLC carcinogenesis. Thus, the detection
      of aberrant DAPK methylation may be helpful in the diagnosis and prognosis of
      NSCLC.

PMID- 24659426
TI  - Cephalomedullary fixation for intertrochanteric fractures: an operative technical
      tip.
AB  - Intertrochanteric fracture is the most common hip fractures in elderly
      population. Cephalomedullary fixation, including proximal femoral nail
      antirotation (PFNA) and gamma nail, is commonly used in the treatment of
      intertrochanteric fractures. One of difficulties encountered in operation is
      insertion of the guide wire to femoral head. The guide wire would always bend and
      flow superiorly away from femoral calcar, and the lag screw and helical blade
      will follow the track and get into superior part of femoral head, not into
      femoral calcar. Here, we are presenting a surgical technique to direct the guide
      wire to right track. When guide wire just passed the tack hole of the nail, the
      rod of nail was slightly tapped down further to allow the superior border of the
      tack hole to touch the guide wire. Therefore, the superior border of the tack
      hole can be used as presser to prevent the wire from deviating upward. Through
      this way, the lag screw and helical blade get a good purchase that docked at
      femoral calcar. After that, the rod of nail was pulled back a little to make the
      wire in the middle of the tack hole, which can facilitate the insertion of the
      PFNA blade or lag screw. Our experience demonstrated that this surgical technique
      reduced the intraoperative risk for patients. 

PMID- 24659427
TI  - Mismatch of AO anatomically shaped distal humeral plate with humeral shaft
      forward flexion angulation in adult Chinese population.
AB  - BACKGROUND: LCP extra-articular distal humerus plate (LCPEA) designed by AO has
      been introduced as an anatomically shaped plate that improves the results of
      surgical fixation in extra-articular distal humeral shaft fractures. However, no
      study analyzed whether LCPEA matches humeral shaft forward flexion angulation
      (FFA). OBJECTIVE: The aims of this study were to evaluate the morphological
      discrepancies between LCPEA and the humeral shaft FFA in Chinese cadaveric dried
      adult humeri and to propose a further design of pre-contoured plates to
      accommodate the FFA. MATERIALS AND METHODS: Forty-four Chinese cadaveric dried
      adult humeri were used for this study. An eight-hole LCPEA was applied to the
      posterior aspect of the distal humerus according to the contour. Mismatches
      between the bone and the plate were recorded. The distance between the inner
      surface of the plate and the underlying humeral dorsal cortex was measured at the
      sites of mismatch. The humeral shaft FFA was measured from the intersection angle
      between tangent lines placed on the dorsal aspect of the 1/3 distal humeral shaft
      and the dorsal ridge of the 2/3 proximal humeral shaft. The location of the apex
      of the FFA was determined by measuring the distance from the most distal point of
      trochlea of humerus to the point of intersection of the FFA tangent lines. The
      distance was defined as forward flexion distance (FFD). RESULTS: Mismatch was
      found at the level of proximal 3-6 holes of LCPEA with an average distance of 6.9
      +/- 3.1 mm (range 2.3-14.0 mm) at the tip of the plate. The FFA was present in
      all specimens. The average FFA was 8.2 degrees  +/- 2.2 degrees  (range 4 degrees
      -13 degrees ), the average FFD was 99.9 +/- 9.6 mm (range 79.2-117.9 mm), and the
      average ratio of FFD to humerus length was 0.33 +/- 0.03 (range 0.27-0.39).
      CONCLUSIONS: A rather consistent pattern of mismatch was found at the proximal
      part of LCPEA. An attempt to fit the plate to the bone at this level may cause a
      gap of the fracture at the opposite cortex. The main reason for the mismatch is
      the existence of the humeral shaft FFA. LCPEA is usually made a bend of about 8
      degrees  between the fourth and the fifth dynamic-compression portion of the
      combination hole in the distal-to-proximal direction.

PMID- 24659428
TI  - Pedobacter seoulensis sp. nov., isolated from soil of a bamboo field.
AB  - A Gram-stain negative, strictly aerobic, motile by gliding, rod-shaped and yellow
      pigmented strain THG-G12T was isolated from soil of a bamboo field in Seoul,
      Republic of Korea. Strain THG-G12T was observed to grow well at 20-28  degrees C
      and pH 7.0-7.5 in the absence of NaCl on nutrient agar. Based on 16S rRNA gene
      sequence comparisons, strain THG-G12T was found to be most closely related to
      Pedobacter ginsengisoli Gsoil 104T (97.5 % sequence similarity), Pedobacter
      steynii WB2.3-45T (97.4 %), Pedobacter metabolipauper WB2.3-71T (97.2 %),
      Pedobacter nyackensis NWG-II14T (97.2 %), Pedobacter caeni LMG 22862T (97.1 %)
      and Pedobacter duraquae WB2.1-25T (97.0 %), but DNA relatedness between strain
      THG-G12T and its phylogenetically closest neighbours was below 9.5 %. The G+C
      content of the genomic DNA was determined to be 39.9 mol%. The only isoprenoid
      quinone detected in strain THG-G12T was menaquinone-7 (MK-7). The major component
      in the polyamine pattern was sym-homospermidine. The major polar lipids were
      found to be phosphatidylethanolamine, unidentified phosphoglycolipids,
      unidentified aminophosphoglycolipids, unidentified aminolipids and unidentified
      lipids. Strain THG-G12T showed the presence of two ceramide
      phosphorylethanolamines (CerPE-2' and CerPE-2"), dihydrosphingosines and an
      unidentified ceramide as the major ceramide. The major fatty acids were
      identified as summed feature 3 (as defined by the MIDI system; C16:1 omega7c
      and/or C16:1 omega6c) and iso-C15:0. These data support the affiliation of strain
      THG-G12T to the genus Pedobacter. The results of physiological and biochemical
      tests enabled strain THG-G12T to be differentiated genotypically and
      phenotypically from the recognized species of the genus Pedobacter. Therefore,
      the novel isolate represents a novel species, for which the name Pedobacter
      seoulensis sp. nov. is proposed, with THG-G12T as the type strain (=KACC 17529T
      =JCM 19363T).

PMID- 24659429
TI  - Frequency and factors associated with use of videolaryngostroboscopy in voice
      disorder assessment.
AB  - OBJECTIVES/HYPOTHESIS: Videolaryngostroboscopy (VLS) is considered an important
      diagnostic tool in the evaluation of patients with laryngeal/voice disorders. We
      evaluated the frequency of, diagnoses associated with, and factors related to VLS
      use in the evaluation of outpatients with laryngeal/voice disorders. STUDY
      DESIGN: Retrospective analysis of a large, national administrative U.S. claims
      database. METHODS: Patients with a laryngeal disorder based on International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      codes from January 1, 2004, to December 31, 2008, seen by an otolaryngologist
      were included. Patient age, gender, geographic region, laryngeal diagnosis,
      comorbid conditions, and whether laryngoscopy or VLS was performed during the
      outpatient otolaryngology visit were collected. RESULTS: A total of 168,444
      unique patients saw an otolaryngologist for 272,112 outpatient visits. Of those,
      6.2% of outpatient otolaryngology visits had a VLS performed. Patient age was
      related to VLS use, with lower odds in the elderly (>= 65 years of age) and those
      0 to 17 years of age. Geographic variation was noted, with higher odds of VLS use
      in urban versus rural areas and greater odds in the Northeast versus the South.
      Laryngeal diagnosis was associated with VLS use with greatest odds for patients
      with multiple diagnoses, vocal fold paralysis, and paresis-followed by
      nonspecific dysphonia and benign vocal fold/laryngeal pathology and followed by
      acute and chronic laryngitis and laryngeal cancer. Patients with gastro
      esophageal reflux (GER) had greater odds of VLS use than patients without GER.
      CONCLUSIONS: VLS was used in 6.2% of outpatient otolaryngology outpatient visits;
      and its use was influenced by multiple factors.

PMID- 24659430
TI  - Oxytocin facilitates the sensation of social stress.
AB  - Essentially all social species experience social stress which can be a catalyst
      for detriments in mental and physical health. The neuropeptide oxytocin (OXT) has
      been shown to produce anxiolytic and antistress effects, thereby qualifying the
      OXT system as a promising drug target in the treatment of stress-related
      disorders. However, recently it has been shown that OXT can have anxiogenic
      effects as well. In the present study, we used functional magnetic resonance
      imaging to scan the brains of 60 healthy men while they were exposed to social
      stress after they received either intranasal OXT (24 IU) or placebo treatment.
      Although OXT administration did not alter salivary cortisol levels as a surrogate
      marker of stress axis activity, our participants initially reported an increment
      in perceived social stress. This behavioral effect was paralleled on the neural
      level by increased activity in the precuneus and cingulate cortex. Taken
      together, our results support the hypothesis that OXT can induce a self
      referential processing bias which facilitates the sensation of social stress in
      the absence of altered endocrine responses.

PMID- 24659431
TI  - Inability of monoclonal anti-light chain antibody to detect clonal B-cells in a
      patient with follicular lymphoma by multicolor flow cytometry.
AB  - BACKGROUND: Our recent publication "Inability of a monoclonal anti-light chain
      antibody to detect clonal plasma cells in a patient with multiple myeloma by
      multicolor flow cytometry," underlined the importance of choice of antibodies to
      detect cytoplasmic light chains. Our present study extends this finding for
      detection of surface immunoglobulin (SIg) light chains on clonal B-cells.
      METHODS: Multicolor flow cytometry was used for analyzing bone marrow (BM) from a
      patient with a CD10-positive follicular lymphoma for infiltrating clonal B-cells.
      RESULTS: In the BM aspirate, B cells could be identified expressing CD19, CD10,
      and high levels of CD20. No SIg light chain expression was found on this
      population of B cells employing monoclonal antibodies. Re-analysis using
      polyclonal antibodies against SIg light chains, revealed presence of lambda light
      chains on the CD10positive B-cells. CONCLUSIONS: These data illustrate when
      antibodies against SIg light chains are employed for B-cell clonality assessment,
      polyclonal antibodies are preferred over monoclonal antibodies.

PMID- 24659432
TI  - A star-shaped perylene diimide electron acceptor for high-performance organic
      solar cells.
AB  - A novel nonplanar star-shaped perylene diimide acceptor with a triphenylamine
      core (S(TPA-PDI)) is explored and applied in solution-processed organic solar
      cells. These solar cells exhibit an encouraging power conversion efficiency of up
      to 3.32%. 

PMID- 24659433
TI  - Survey of cyanobacterial toxins in Czech water reservoirs--the first observation
      of neurotoxic saxitoxins.
AB  - The environmental occurrence and concentrations of cyanobacterial toxins
      (cyanotoxins) were investigated in the Czech Republic. Concentrations of
      microcystins (MCs), cylindrospermopsin (CYN) or saxitoxins (STXs) were determined
      immunochemically by ELISA assays in 30 water samples collected from the surface
      layers of 19 reservoirs during the summer season of 2010. MCs were detected in 18
      reservoirs and 83 % of samples, with median and maximal concentration being 1.5
      and 18.6 MUg/L, respectively. The high frequency of MC occurrence coincided with
      prevalence of cyanobacterium Microcystis sp., which was detected in 87 % samples,
      followed by Dolichospermum (Anabaena) sp. observed in 33 % samples. CYN was
      detected by ELISA only in one sample at a concentration of 1.2 MUg/L. STXs
      presence was indicated for the first time in Czech water reservoirs when the
      toxins were found at low concentrations (0.03-0.04 MUg/L) in two samples (7 %)
      collected from two different reservoirs, where STXs co-occurred with MCs and
      eventually also with CYN. In both STX-positive samples, the phytoplankton
      community was dominated by Microcystis sp., but Dolichospermum sp. and/or
      Aphanizomenon sp. were also present as putative producers of STX and/or CYN.
      Cyanotoxins commonly occurred in Czech water reservoirs, and MCs frequently at
      concentrations possibly associated with human health risks. MCs were the most
      prevalent and abundant cyanotoxins, but also other cyanotoxins were detected,
      though sporadically. Further research and regulatory monitoring of cyanotoxins
      other than MCs is therefore required.

PMID- 24659434
TI  - Adsorption and photocatalytic decomposition of roxarsone by TiO2 and its
      mechanism.
AB  - Roxarsone (3-nitro-4-hydroxyphenylarsonic acid) has been widely used as organic
      arsenic additive in animal industry. In this study, the adsorption of roxarsone
      on TiO2 under dark conditions, the photocatalytic decomposition of roxarsone
      under UV/TiO2, and the possible photocatalytic pathway were investigated. At the
      initial concentration of 5-35 mg/L, the adsorption of roxarsone fitted well with
      the pseudo-second-order kinetics. The isotherms analysis showed that the Langmuir
      model was better than the Freundlich and Dubinin-Radushkevich models for
      describing the adsorption process. After 7 h of photocatalytic decomposition, a
      complete disappearance of roxarsone was achieved. The pH value has a significant
      effect on both adsorption and photocatalytic decomposition of roxarsone. The
      results of high-performance liquid chromatography-hydride generation-atomic
      fluorescence spectrometry (HPLC-HG-AFS) and gas chromatography-mass spectrometry
      (GC/MS) analyses proved the cleavage of the As-C bond during the photocatalytic
      decomposition process by TiO2 and the intermediates of the decomposition. Based
      on the results, a possible photocatalytic decomposition pathway was proposed.

PMID- 24659435
TI  - Column dynamic studies and breakthrough curve analysis for Cd(II) and Cu(II) ions
      adsorption onto palm oil boiler mill fly ash (POFA).
AB  - This paper investigates the adsorption characteristics of palm oil boiler mill
      fly ash (POFA) derived from an agricultural waste material in removing Cd(II) and
      Cu(II) from aqueous solution via column studies. The performance of the study is
      described through the breakthrough curves concept under relevant operating
      conditions such as column bed depths (1, 1.5, and 2 cm) and influent metal
      concentrations (5, 10, and 20 mg/L). The Cd(II) and Cu(II) uptake mechanism is
      particularly bed depth- and concentration-dependant, favoring higher bed depth
      and lower influent metal concentration. The highest bed capacity of 34.91 mg
      Cd(II)/g and 21.93 mg Cu(II)/g of POFA was achieved at 20 mg/L of influent metal
      concentrations, column bed depth of 2 cm, and flow rate of 5 mL/min. The whole
      breakthrough curve simulation for both metal ions were best described using the
      Thomas and Yoon-Nelson models, but it is apparent that the initial region of the
      breakthrough for Cd(II) was better described using the BDST model. The results
      illustrate that POFA could be utilized effectively for the removal of Cd(II) and
      Cu(II) ions from aqueous solution in a fixed-bed column system.

PMID- 24659436
TI  - Copolymerization of 2,4-dichlorophenol with humic substances by oxidative and
      photo-oxidative biomimetic catalysis.
AB  - We evaluated the catalytic activity of a water-soluble iron-porphyrin in an
      oxidative coupling reaction to form covalent bonds between 2,4-dichlorophenol
      (2,4-DCP) and humic molecules. The biomimetic catalysis in the presence of H2O2
      was tested in the dark and in daylight, and changes in reaction products were
      revealed by high-performance liquid chromatography (HPLC) and nuclear magnetic
      resonance (NMR) spectroscopy. In all conditions, iron-porphyrin was effective in
      promoting complete disappearance of 2,4-DCP, although catalyst activity was
      enhanced in daylight (with a maximum turnover number of 85.13). Further evidence
      of the occurred covalent coupling between 2,4-DCP and humic molecules was
      revealed by diffusion-ordered nuclear magnetic resonance (DOSY-NMR) spectroscopy
      that showed a reduced diffusivity of 2,4-DCP after the catalytic reaction. These
      findings indicate that iron-porphyrin is an efficient catalyst for the covalent
      binding of polyhalogenated phenols to humic molecules, thereby suggesting that
      the copolymerization reactions may become a useful technology to remediate soils
      and waters contaminated by halogenated phenols and their analogues.

PMID- 24659437
TI  - Factorial design analysis for COD removal from landfill leachate by photoassisted
      Fered-Fenton process.
AB  - The Fered-Fenton process has been shown to be an effective method for leachate
      treatment, but it still faces problems of inadequate regeneration of ferrous ion.
      However, the use of the photoassisted Fered-Fenton process could overcome this
      difficulty and improve the efficiency of chemical oxygen demand (COD) removal
      since photoassisted Fered-Fenton process induces the production of hydroxyl
      radicals from the regeneration of ferrous ions and the reaction of hydrogen
      peroxide with UV light. As there are so many operating parameters in
      photoassisted Fered-Fenton process, it is necessary to develop a mathematical
      model in order to produce the most economical process. In the present study, a
      factorial design was carried out to evaluate leachate treatment by photoassisted
      Fered-Fenton process. The influence of the following variables: H2O2
      concentration, Fe(2+) concentration, current density, and initial pH in the
      photoassisted Fered-Fenton process was investigated by measuring COD removal
      efficiencies after 60-min reaction. The relationship between COD removal and the
      most significant independent variables was established by means of an
      experimental design. The H2O2 concentration, Fe(2+) concentration, initial pH,
      and the interaction effect between current density and initial pH were all
      significant factors. The factorial design models were derived based on the COD
      removal efficiency results and the models fit the data well.

PMID- 24659438
TI  - Screening for birth weight deviations by second and third trimester ultrasound
      scan.
AB  - OBJECTIVE: The aim of this article was to predict small for gestational age (SGA,
      at or less than the fifth birth weight percentile) and large for gestational age
      (LGA, at or greater than the 95th birth weight percentile) fetuses by using
      maternal and fetal parameters from the second and third trimester ultrasound
      examinations. METHOD: This article is a retrospective cohort study on 1979
      singleton pregnancies that had a routine 20 to 24 weeks anomaly and a 30 to 34
      weeks growth ultrasound scans. SGA delivered before 30 gestational weeks were
      excluded. RESULTS: Second trimester estimated fetal weight (EFW2 ), uterine
      arteries pulsatility index (PI), and maternal pregnancy characteristics were
      predictive for SGA (SGA second trimester model: R(2)  = 0.225, area under the
      curve [AUC] = 0.815) and LGA (LGA second trimester model: R(2)  = 0.203, AUC =
      0.793). Third trimester EFW (EFW3 ), EFW2 , uterine arteries PI2 , umbilical PI,
      and maternal pregnancy characteristics improved the prediction of SGA (SGA
      combined model: R(2)  = 0.423, AUC = 0.896) and LGA (LGA combined model: R(2)  =
      0.383, AUC = 0.882). Contingent screening with risk stratification by the second
      trimester model performed equally well for SGA (AUC = 0.882) and LGA (AUC =
      0.861) as the combined models. CONCLUSION: Second trimester model performs well
      in the prediction of SGA and LGA. The addition of third trimester scan offers
      substantial improvement. Contingency screening is feasible with similar
      effectiveness.

PMID- 24659439
TI  - Use of multiple indicators to assess the environmental quality  of urbanized
      aquatic surroundings in San Luis, Argentina.
AB  - Urbanization can cause significant changes in the integrity of fluvial
      ecosystems, which makes it necessary to assess environmental conditions of areas
      where population growth rates are high. A study of the environmental quality of
      Chorrillos River (San Luis-Argentina) and its tributaries was carried out in
      order to evaluate the potential effect of an urbanization gradient. Six sites
      were sampled along the main course and tributaries of the river. Urbanization
      variables were measured and included to calculate an Urbanization Index. Physical
      chemical analyses were performed in water samples to evaluate water quality
      through the use of a simplified index of water quality (SIWQ). Plants,
      macroinvertebrates, and amphibians metrics were used to assess the biological
      state of the studied sites. The Urbanization Index varied significantly between
      sites and was significantly correlated to the SIWQ. However, no significant
      correlations were found between SIWQ and macroinvertebrates and amphibians
      variables. Water quality of Chorrillos River and its tributaries is good, but it
      is affected by anthropic influences as reflected by the declining of SIWQ values.
      Although biological sampling constitutes an important tool in the assessment of
      water quality of rivers, in this report biological results were not conclusive.

PMID- 24659440
TI  - Aggression in schools: psychosocial outcomes of bullying among Indian
      adolescents.
AB  - OBJECTIVES: To examine the prevalence of school bullying and to investigate the
      behavioral, emotional, socio-economic and demographic correlates of bullying
      behaviors among Indian school going adolescents. METHODS: Self-reports on
      bullying involvement were collected from 9th to 10th class students (N = 209;
      Mean = 14.82 y, SD = 0.96) from Government and Private schools of a north Indian
      city. Four groups of adolescents were identified: bullies, victims, bully
      victims, and non-involved students. The self concept of the child was measured by
      the Indian adaptation of the Piers Harris Children's Self Concept Scale (CSCS)
      and emotional and behavioral difficulties by the Youth self report measure of the
      Strengths and Difficulties Questionnaire. RESULTS: The overall prevalence of any
      kind of bullying behavior was 53 %. One-fifth (19.2 %) of the children were
      victims of bullying. Boys were more likely to be bully-victims (27.9 %) and girls
      were more likely to be victims (21.6 %). Bullying status was significantly
      related to the total self concept scores of the students (F = 5.12, P = 0.002).
      Victimized adolescents reported the lowest self concept scores. Bully-victims had
      a higher risk for conduct problems and hyperactivity and were the most likely to
      have academic difficulties. Bullies had relatively better school grades and high
      self esteem but had higher risk for hyperactivity and conduct problems as
      compared to controls. CONCLUSIONS: Bullying and victimization was widespread
      among the Indian school going youth. Given the concurrent psychosocial adjustment
      problems associated with bullying, there is an urgent need for developing
      intervention programs and sensitizing school personnel.

PMID- 24659441
TI  - Additional opportunities for Integrated Child Development Services (ICDS) in
      India.

PMID- 24659442
TI  - Hepatitis A in children- clinical course, complications and laboratory profile:
      correspondence.

PMID- 24659443
TI  - Hepatitis A in children- clinical course, complications and laboratory profile:
      authors' reply.

PMID- 24659444
TI  - Serum amyloid A3 exacerbates cancer by enhancing the suppressive capacity of
      myeloid-derived suppressor cells via TLR2-dependent STAT3 activation.
AB  - Myeloid-derived suppressor cells (MDSCs), which suppress diverse innate and
      adaptive immune responses and thereby provide an evasion mechanism for tumors,
      are emerging as a key population linking inflammation to cancer. Although many
      inflammatory factors that induce MDSCs in the tumor microenvironment are known,
      the crucial components and the underlying mechanisms remain elusive. In this
      study, we proposed a novel mechanism by which serum amyloid A3 (SAA3), a well
      known inflammatory factor, connects MDSCs with cancer progression. We found that
      SAA3 expression in BALB/c mice increased in monocytic MDSCs (Mo MDSCs) with tumor
      growth. The induction of SAA3 by apo-SAA treatment in Mo MDSCs enhanced their
      survival and suppressive activity, while it inhibited GM-CSF-induced
      differentiation. Endogenous SAA3 itself contributed to the increase in the
      survival and suppressive activity of Mo MDSCs. We demonstrated that SAA3 induced
      TLR2 signaling, in turn increasing the autocrine secretion of TNF-alpha, that led
      to STAT3 activation. In addition, activated STAT3 enhanced the suppressive
      activity of Mo MDSCs. Furthermore, SAA3 induction in Mo MDSCs contributed to
      accelerating tumor progression in vivo. Collectively, these data suggest a novel
      mechanism by which Mo MDSCs mediate inflammation through SAA3-TLR2 signaling and
      thus exacerbate cancer progression by a STAT3-dependent mechanism. 

PMID- 24659445
TI  - Detection of breast abnormality from thermograms using curvelet transform based
      feature extraction.
AB  - Breast cancer is one of the leading causes for high mortality rates among young
      women, in the developing countries. Currently mammography is used as the gold
      standard for screening breast cancer. Due to its inherent disadvantages,
      alternative techniques are being considered for this purpose. Breast thermography
      is one such imaging modality, which represents the temperature variations of
      breast in the form of intensity variations on an image. In the last decade,
      several studies have been made to evaluate the potential of breast thermograms in
      detecting abnormal breast conditions, from an image processing view point. This
      paper proposes a curvelet transform based feature extraction method for automatic
      detection of abnormality in breast thermograms. Statistical and texture features
      are extracted from thermograms in the curvelet domain, to feed a support vector
      machine for automatic classification. The classifier detects abnormal thermograms
      with an accuracy of 90.91 %. The results of the study indicate that texture
      features have better potential to detect abnormality in breast thermograms, when
      extracted in the multiresolution curvelet domain.

PMID- 24659446
TI  - Burnout and self-reported quality of care in community mental health.
AB  - Staff burnout is widely believed to be problematic in mental healthcare, but few
      studies have linked burnout directly with quality of care. The purpose of this
      study was to examine the relationship between burnout and a newly developed scale
      for quality of care in a sample of community mental health workers (N=113). The
      Self-Reported Quality of Care scale had three distinct factors (Client-Centered
      Care, General Work Conscientiousness, and Low Errors), with good internal
      consistency. Burnout, particularly personal accomplishment, and to a lesser
      extent depersonalization, were predictive of overall self-rated Quality of Care,
      over and above background variables.

PMID- 24659447
TI  - Outcome of fetoscopic laser ablation for twin-to-twin transfusion syndrome in
      dichorionic-triamniotic triplets compared with monochorionic-diamniotic twins.
AB  - OBJECTIVE: To compare outcome of dichorionic-triamniotic (DCTA) triplet
      gestations with that of a paired cohort of monochorionic-diamniotic (MCDA) twin
      gestations undergoing laser therapy for treatment of twin-to-twin transfusion
      syndrome (TTTS). METHODS: All DCTA triplets treated at four referral centers
      between specified dates were included. A matched cohort group of MCDA twin
      gestations affected by TTTS was used for comparison. RESULTS: Sixteen sets of
      DCTA triplets treated with laser photocoagulation of placental anastomoses were
      compared with 32 matched sets of MCDA twins. All of the 'singleton' fetuses in
      the triplet gestations survived to birth and to the end of the neonatal period.
      There were no differences in single or double survival or the rate of non
      survivors to birth and at age 28 days. A mean 3-week difference was found in the
      procedure-to-delivery interval in DCTA triplets vs MCDA twins (60 +/- 35.8 days
      vs 83.6 +/- 33.2 days; P = 0.029). A mean difference of 3 weeks was also found in
      the gestational age at delivery in DCTA triplets vs MCDA twins (28.5 +/- 3.5
      weeks vs 31.9 +/- 5 weeks; P = 0.024). A similar post-laser fetal growth pattern
      in donors and recipients of both groups was noted. CONCLUSIONS: DCTA triplet
      gestations with TTTS have a similar rate of post-laser survival but deliver
      earlier than can be expected for twins treated with laser. These findings have
      potential implications for the risk of prematurity and long-term outcomes.

PMID- 24659448
TI  - Reevaluation of survival and prognostic factors in pathologic  stage I lung
      adenocarcinoma by the new 2009 TNM classification.
AB  - The incidence of lung adenocarcinoma has been increased significantly year by
      year. In this histologic type, complete surgical resection is commonly chosen as
      treatment method at the initial stages. However, the postoperative survival rate
      remains unsatisfactory even within the stage I. The purpose of this study is to
      investigate the factors related with prognosis in stage I lung adenocarcinoma
      after surgical resection. In this manuscript, a retrospective study was
      performed. Survival rates were calculated by the Kaplan-Meier method, and for
      multivariate analyses, Cox proportional hazards regression model was used. The
      results indicated that a total of 531 patients were included. Overall 5-year
      survival was 81.2 %. Age, sex, pathologic stage, T category, tumor size,
      differentiation, necrosis, visceral pleural invasion (VPI), lymphatic vessel or
      vascular invasion, and serum carcinoembryonic antigen (CEA) were significantly
      associated with 5-year overall survival of the patients with Kaplan-Meier
      analysis. Moreover, on multivariate analyses, seven variables were shown to be
      independent prognostic factors, including differentiation (hazard ratios (HR),
      1.357), VPI (HR, 0.551), lymphatic vessel or vascular invasion (HR, 0.533),
      necrosis (HR, 1.671), age (HR, 1.519), pathological stage (HR, 4.477), and CEA
      (HR, 2.099). In conclusion, the most important prognostic factor is pathologic
      stage. Other adverse prognostic factors include differentiation, VPI, lymphatic
      vessel or vascular invasion, necrosis, age, and CEA.

PMID- 24659449
TI  - Glutathione S-transferase gene polymorphisms and susceptibility  to chronic
      myeloid leukemia.
AB  - Glutathione S-transferase (GST), a phase II metabolizing enzyme, plays an
      important role in the cellar defense system, and its activity may modulate
      leukemia risk. A large body of evidence has shown the possible relevance of
      functional polymorphisms of the genes that encode GSTs MU, pi, and theta (GSTM1,
      GSTP1, and GST1, respectively) to the genetic susceptibility of chronic myeloid
      leukemia (CML). Because of the lack of available conclusive data, we performed a
      meta-analysis of all relevant available studies to derive a more precise
      estimation of the relationship. A comprehensive literature search of PubMed and
      Web of Knowledge electronic databases was conducted to collect relevant studies
      until December 20, 2013, and the extracted data were statistically analyzed using
      Review Manager version 5.2. Finally, 16 eligible studies were identified in the
      literature. The GSTT1 null genotype was associated with an increased risk of CML,
      as were the double null GSTT1 and GSTM1 genotypes. These findings suggest that
      heritable GST status influences the risk of developing CML and that more
      attention should be paid to carriers of these susceptibility genes.

PMID- 24659450
TI  - Diagnostic accuracy of contrast-enhanced ultrasound for renal cell carcinoma: a
      meta-analysis.
AB  - This meta-analysis aimed to identify the accuracy of contrast-enhanced
      ultrasonography (CEUS) for the diagnosis of renal cell carcinoma (RCC). We
      searched PubMed, Web of Science, Google Scholar, Cochrane Library, CISCOM,
      CINAHL, EBSCO, and CBM databases from inception through August 1, 2013 without
      language restrictions. Meta-analysis was conducted using STATA version 12.0 and
      Meta-Disc version 1.4 softwares. We calculated the summary statistics for
      sensitivity (Sen), specificity (Spe), positive and negative likelihood ratio
      (LR+/LR-), diagnostic odds ratio (DOR), and receiver operating characteristic
      (SROC) curve. Eleven studies that met all inclusion criteria were included in
      this meta-analysis. A total of 567 RCC patients and 313 patients with benign
      renal tumors were assessed. All renal lesions were histologically confirmed after
      CEUS. The pooled Sen was 0.88 (95 %CI = 0.85 ~ 0.90); the pooled Spe was 0.80 (95
      %CI = 0.75 ~ 0.85). The pooled LR+ was 4.30 (95 %CI = 2.65 ~ 6.99); the pooled
      negative LR- was 0.11 (95 %CI = 0.05 ~ 0.22). The pooled DOR of CEUS in the
      diagnosis of RCC was 46.97 (95 % CI = 16.72 ~ 131.97). The area under the SROC
      curve was 0.922 (standard error [SE] = 0.039). We found no evidence for
      publication bias (t = -1.00, P = 0.342). Our meta-analysis indicates that CEUS
      may have high diagnostic accuracy in differential diagnosis between benign and
      malignant renal tumors. Thus, CEUS may be a good tool for the diagnosis of RCC.

PMID- 24659451
TI  - Depicting the inner and outer nose: the representation of the nose and the nasal
      mucosa on the human primary somatosensory cortex (SI).
AB  - The nose is important not only for breathing, filtering air, and perceiving
      olfactory stimuli. Although the face and hands have been mapped, the
      representation of the internal and external surface of the nose on the primary
      somatosensory cortex (SI) is still poorly understood. To fill this gap functional
      magnetic resonance imaging (fMRI) was used to localize the nose and the nasal
      mucosa in the Brodman areas (BAs) 3b, 1, and 2 of the human postcentral gyrus
      (PG). Tactile stimulation during fMRI was applied via a customized pneumatically
      driven device to six stimulation sites: the alar wing of the nose, the lateral
      nasal mucosa, and the hand (serving as a reference area) on the left and right
      side of the body. Individual representations could be discriminated for the left
      and right hand, for the left nasal mucosa and left alar wing of the nose in BA 3b
      and BA 1 by comparing mean activation maxima and Euclidean distances. Right-sided
      nasal conditions and conditions in BA 2 could further be separated by different
      Euclidean distances. Regarding the alar wing of the nose, the results concurred
      with the classic sensory homunculus proposed by Penfield and colleagues. The
      nasal mucosa was not only determined an individual and bilateral representation,
      its position on the somatosensory cortex is also situated closer to the caudal
      end of the PG compared to that of the alar wing of the nose and the hand. As SI
      is commonly activated during the perception of odors, these findings underscore
      the importance of the knowledge of the representation of the nasal mucosa on the
      primary somatosensory cortex, especially for interpretation of results of
      functional imaging studies about the sense of smell.

PMID- 24659452
TI  - Synthesis of nanoscale titania embedded in MIL-101 for the adsorption and
      degradation of volatile pollutants with thermal desorption gas chromatography and
      mass spectrometry detection.
AB  - Nanoscale anatase titania was embedded within the porous chromium terephthalate
      MIL-101 under low-temperature hydrothermal treatment. The metal-organic framework
      shell acting as host matrix can effectively prevent the titania nanoparticles
      from aggregating and enable a good dispersion of these nanoparticles. The X-ray
      diffraction spectra, transmission electron micrography and X-ray photoelectron
      spectra clearly showed successful impregnation of the nano-sized anatase titania
      within the body of MIL-101. The resulting TiO2/MIL-101 nanocomposite was
      considered as bifunctional material with abundant adsorptive domains and
      catalytic domains, and was packed in a quartz tube as a convenient trapping and
      photocatalytic reactor for hazardous volatile pollutants. The composite showed
      great potential for adsorptive and photocatalytic degradation of these volatile
      pollutants, such as formaldehyde and o-xylene, which were online monitored by
      thermal desorption gas chromatography with mass spectrometric detection.

PMID- 24659453
TI  - Correlation of synovial cytokine expression with quality of cells used for
      autologous chondrocyte implantation in human knees.
AB  - The cell quality plays a decisive role in autologous chondrocyte implantation
      (ACI). Aim of the study was the analysis of in vivo interactions between synovial
      concentrations of cytokines and cell quality used for ACI. Knee lavage fluids of
      patients undergoing an ACI were examined for total protein content (TPC) and by
      ELISA for levels of basic fibroblast growth factor (bFGF), insulin-like growth
      factor 1, bone morphogenetic proteins 2 and 7 (BMP-2 and BMP-7). Cell quality
      following amplification for ACI was determined by surface expression of CD44,
      aggrecan, collagen type II and evaluation of cell characteristics. Data of 17
      patients were supplemented by epidemiological parameters and clinical scores
      (IKDC, Lysholm, pain strength, subjective knee function). CD44 expression was
      positively associated with TPC and bFGF, and negatively linked to BMP-2 levels (p
      < 0.01). In contrast, expression of collagen type II did not show any
      statistically significant correlations with synovial protein concentrations. TPC
      was positively associated with intraarticular bFGF levels and pain strength (p <
      0.01), both indicators for osteoarthritis (OA). Correlating with the negative
      relation of TPC and BMP-2, subjective knee function after 1 year was positively
      linked to intraarticular BMP-2 concentrations (p < 0.001). Similarly, expression
      of collagen type II indicated a favorable clinical result reaching statistical
      significance in case of pain strength (p < 0.01). Initially increased bFGF levels
      and CD44 expression indicated a worse clinical outcome after 1 year (IKDC,
      Lysholm Scores, pain strength). Surface expression of CD44 on chondrocytes used
      for ACI was negatively associated with synovial BMP-2 and positively to TPC and
      bFGF indicating catabolic synovial conditions. These correlations were also
      reflected by clinical outcome parameters.

PMID- 24659454
TI  - An evaluation of the delayed effect of intra-articular injections of lidocaine
      (2%) on articular cartilage: an experimental study in rabbits.
AB  - Lidocaine is commonly injected into the joints as an analgesic. The aim of the
      present study was to evaluate the delayed effect of intra-articular injections of
      lidocaine (2%) on articular cartilage in rabbit knees. Ten rabbits were divided
      into two groups, each group containing five animals. Two milliliters of normal
      saline solution was injected into both knee joints of animals in group one
      (control group), and 2 ml of lidocaine was injected into both knee joints of
      animals in group two (case group). After 8 weeks, the articular cartilage of the
      distal femur was harvested and analyzed through confocal microscopy and real-time
      polymerase chain reaction to evaluate the viability and function of chondrocytes,
      respectively. Confocal microscopy showed a significant decrease in the number of
      live cells caused by lidocaine (P <= 0.001). The changes in gene expression of
      collagen types II (COL II) and aggrecan were significant in group two (P = 0.008
      and P = 0.002, respectively). According to the results, the delayed in vivo
      effect of lidocaine on chondrocyte is to reduce live chondrocytes and change in
      the gene expression of COL II and aggrecan.

PMID- 24659455
TI  - Definitive management of significant soft tissue loss associated with open
      diaphyseal fractures utilising circular external fixation without free tissue
      transfer, a comprehensive review of the literature and illustrative case.
AB  - Accepted management of diaphyseal fractures associated with significant tissue
      loss is rigid intramedullary stabilisation with free or rotational
      musculocutaneous flap coverage. Circular external fixation is a powerful tool in
      the management of limb trauma and with recent advances has been developed to
      provide multiple techniques for which even massive tissue loss can be addressed
      without the need for free tissue transfer. Gradual and acute shortening, acute
      fracture deformation and gradual lengthening with restoration of deformity
      combined with distraction tissue histiogenesis can provide the surgeon with an
      array of options which can be precisely tailored to the particular personality of
      a severe open diaphyseal fracture.

PMID- 24659456
TI  - Formation of chlorinated species through reaction of SO2 with NaClO2 powder and
      their role in the oxidation of NO and Hg0.
AB  - This study examines gaseous chlorinated species generated from the reaction of
      sulfur dioxide (SO2) with sodium chlorite powder (NaClO2(s)) to obtain insight
      into the propensity of this process to enhance NO and Hg0 oxidation. A packed bed
      reactor containing NaClO2(s) was used and the reaction temperature was set to 130
      degrees C. Initially, we determined that the presence of SO2 enhances the
      oxidation of NO and Hg0 by reaction with NaClO2(s). We then introduced NO2 into
      the gas mixture as a radical scavenger and determined that the chlorinated
      species generated by the reaction of SO2 with NaClO2(s) are OClO, Cl, ClO, and
      Cl2. Based on these results, we suggest that such gaseous chlorinated ones are
      responsible for the enhancement of NO and Hg0 oxidation.

PMID- 24659457
TI  - Evaluation of spatial-temporal variations and trends in surface water quality
      across a rural-suburban-urban interface.
AB  - Water quality degradation is often a severe consequence of rapid economic
      expansion in developing countries. Methods to assess spatial-temporal patterns
      and trends in water quality are essential for guiding adaptive management efforts
      aimed at water quality remediation. Temporal and spatial patterns of surface
      water quality were investigated for 54 monitoring sites in the Wen-Rui Tang River
      watershed of eastern China to identify such patterns in water quality occurring
      across a rural-suburban-urban interface. Twenty physical and chemical water
      quality parameters were analyzed in surface waters collected once every 4-8 weeks
      from 2000 to 2010. Temporal and spatial variations among water quality parameters
      were assessed between seasons (wet/dry) and among major land use zones
      (urban/suburban/rural). Factor analysis was used to identify parameters that were
      important in assessing seasonal and spatial variations in water quality. Results
      revealed that parameters related to organic pollutants (dissolved oxygen (DO),
      chemical oxygen demand (manganese) (COD(Mn)), and 5-day biochemical oxygen demand
      (BOD5)), nutrients (ammonia nitrogen (NH4 +-N), total nitrogen (TN), total
      phosphorus (TP)), and salt concentration (electrical conductivity (EC)) were the
      most important parameters contributing to water quality variation. Collectively,
      they explained 70.9 % of the total variance. A trend study using the seasonal
      Kendall test revealed reductions in COD(Mn), BOD5, NH4 +-N, petrol, V-phen, and
      EC concentrations over the 11-year study period. Cluster analysis was employed to
      evaluate variation among 14 sampling sites representative of dominant land use
      categories and indicated three, three, and four clusters based on organic,
      nutrient, and salt water quality characteristics, respectively. Factors that are
      typically responsible for water quality degradation (including population,
      topography, and land use) showed no strong correlation with water quality trends
      implying considerable point source inputs in the watershed. The results of this
      study help inform ongoing water quality remediation efforts by documenting trends
      in water quality across various land use zones.

PMID- 24659458
TI  - Treatment of dilute methylene blue-containing wastewater by coupling sawdust
      adsorption and electrochemical regeneration.
AB  - In the present work, the coupling of adsorption and electrochemical oxidation on
      a boron-doped diamond (BDD) electrode to treat solutions containing dyes is
      studied. This coupling may be convenient for the treatment of diluted pollutant
      that is limited by the low rate of electrooxidation due to mass-transfer
      limitation. A pre-concentration step by adsorption could minimize the design of
      the electrochemical reactor. The adsorbent chosen was mixed with softwood
      sawdust, and methylene blue was chosen as the model dye molecule. Isotherms of
      adsorption and kinetics were investigated as well as the effects of current
      density and regeneration time. The BDD electrochemical oxidation of methylene
      blue adsorbed onto sawdust led simultaneously to its degradation and sawdust
      regeneration for the next adsorption. It was observed that multiple adsorption
      and electrochemical regeneration cycles led to an enhancement of adsorption
      capacity of the sawdust. This study demonstrated that adsorption-electrochemical
      degradation coupling offers a promising approach for the efficient elimination of
      organic dyes from wastewater.

PMID- 24659459
TI  - Sequence-specific resonance assignments of human TAF15-RRM and TAF15-RRM-RanBP2.
AB  - Human TATA binding protein associated factor 2 N (TAF15) is a RNA/DNA binding
      protein involved in many aspects of RNA and DNA metabolism. TAF15 contains an N
      terminal transcriptional activation domain and C-terminal region comprising the
      RNA recognition motif (RRM) and RanBP2 type zinc finger domains with interspersed
      RGG motifs. In this study we report the complete backbone and side chain
      resonance assignments of human TAF15-RRM and backbone assignments of TAF15-RRM
      RanBP2.

PMID- 24659460
TI  - (1)H, (13)C and (15)N resonance assignments of the RodA hydrophobin from the
      opportunistic pathogen Aspergillus fumigatus.
AB  - Hydrophobins are fungal proteins characterised by their amphipathic properties
      and an idiosyncratic pattern of eight cysteine residues involved in four
      disulphide bridges. The soluble form of these proteins spontaneously self
      assembles at hydrophobic/hydrophilic interfaces to form an amphipathic monolayer.
      The RodA hydrophobin of the opportunistic pathogen Aspergillus fumigatus forms an
      amyloid layer with a rodlet morphology that covers the surface of fungal spores.
      This rodlet layer bestows hydrophobicity to the spores facilitating their
      dispersal in the air and rendering the conidia inert relative to the human immune
      system. As a first step in the analysis of the solution structure and self
      association of RodA, we report the (1)H, (13)C and (15)N resonance assignments of
      the soluble monomeric form of RodA.

PMID- 24659461
TI  - A liquid chromatography-tandem mass spectrometry-based targeted proteomics
      approach for the assessment of transferrin receptor levels in breast cancer.
AB  - PURPOSE: Overexpression of human transferrin receptor (TfR) has been described
      qualitatively in various cancers, including breast cancer. Since TfR is also
      expressed to some extent under normal physiological conditions, increase of
      specificity and reproducibility in TfR quantification could improve the early
      detection and prognostic evaluation of cancers. EXPERIMENTAL DESIGN: A LC-MS/MS
      based targeted proteomics assay was developed for the determination of TfR in
      human breast cells and tissue samples. RESULTS: We selected the tryptic peptide
      681VEYHFLSPYVSPK693 as the surrogate peptide for quantification and used a stable
      isotope-labeled synthetic peptide with this sequence as an internal standard.
      Quality control data indicated acceptable accuracy and precision. Finally, this
      assay was successfully applied to the quantitative analysis of TfR in three
      breast cell lines and 36 matched pairs of breast tissue samples. The experimental
      values were compared with those obtained from conventional analytical methods,
      including immunofluorescence microscopy, Western blotting, flow cytometry, and
      immunohistochemistry. CONCLUSIONS AND CLINICAL RELEVANCE: Not only is the LC
      MS/MS-based targeted proteomics assay a more accurate method for the
      determination of TfR levels, but may afford more reliable quantification of TfR
      at low concentrations in clinical practice.

PMID- 24659462
TI  - WhatSAP - 2B4 sends mixed messages in the absence of SAP.
AB  - 2B4 (CD244), a member of the SLAM-related receptor family, has important immuno
      regulatory functions including coactivating the cytotoxicity and cytokine
      secretion of NK cells. Immune modulation by 2B4 is dependent on the small
      intracellular signaling molecule SAP. In patients suffering from X-linked
      lymphoproliferative disease (XLP1), SAP is nonfunctional, not only abolishing the
      activating function of 2B4, but rendering this receptor inhibitory. In this issue
      of European Journal of Immunology, Meazza et al. [Eur. J. Immunol. 2014. 44: 1526
      1534.] demonstrate that 2B4-mediated inhibition in NK cells from XLP1 patients is
      selective. While the activation of NK cells via ITAM-based receptors is blocked
      by inhibitory 2B4, DNAM-1, and NKG2D-dependent NK-cell activation is not affected
      by SAP deficiency. These findings provide an important insight into the different
      defective NK-cell functions in XLP1 patients and demonstrate the differential
      integration of redundant receptor signaling pathways in NK cells. 

PMID- 24659464
TI  - Serum vascular endothelial growth factor, transforming growth factor beta1, and
      nitric oxide levels in patients with psoriasis vulgaris: their correlation to
      disease severity.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), transforming growth factor
      beta1 (TGF-beta1), and nitric oxide (NO) have been reported to be contributory
      factors to the pathogenesis of psoriasis vulgaris. In the current study, we aimed
      to investigate the association between the levels of VEGF, TGF-beta1, and NO and
      psoriasis severity (as expressed by psoriasis area severity index, PASI).
      METHODS: Fifty-eight patients with psoriasis vulgaris and twenty-two controls
      were included in the study. The serum levels of VEGF and TGF-beta1 were estimated
      by ELISA technique. The serum levels of NO were determined by colorimetric
      method. RESULTS: The serum levels of VEGF, TGF-beta1, and NO were significantly
      higher in patients than controls. Moreover, the serum levels of the studied
      biochemical variables in patients with severe disease activity were significantly
      higher than mild cases. The duration of disease showed significant positive
      correlations with each VEGF (r = 0.35, P < 0.01) and TGF-beta1 (r = 0.41, P <
      0.05). In addition, the PASI score was significantly positively correlated with
      VEGF (r = 0.65, P < 0.001), TGF-beta1 (r = 0.31, P < 0.05), and NO (r = 0.51, P <
      0.001). CONCLUSION: These findings suggest an association between psoriasis
      disease severity and serum levels of VEGF, TGF-beta1, and NO, which can be
      recognized as markers of the psoriasis severity. The modulation of their
      production may represent a therapeutic potential strategy for psoriasis.

PMID- 24659465
TI  - Intronic splicing mutations in PTCH1 cause Gorlin syndrome.
AB  - Gorlin syndrome is an autosomal dominant disorder characterized by multiple early
      onset basal cell carcinoma, odontogenic keratocysts and skeletal abnormalities.
      It is caused by heterozygous mutations in the tumour suppressor PTCH1. Routine
      clinical genetic testing, by Sanger sequencing and multiplex ligation-dependent
      probe amplification (MLPA) to confirm a clinical diagnosis of Gorlin syndrome,
      identifies a mutation in 60-90 % of cases. We undertook RNA analysis on
      lymphocytes from ten individuals diagnosed with Gorlin syndrome, but without
      known PTCH1 mutations by exonic sequencing or MLPA. Two altered PTCH1 transcripts
      were identified. Genomic DNA sequence analysis identified an intron 7 mutation
      c.1068-10T>A, which created a strong cryptic splice acceptor site, leading to an
      intronic insertion of eight bases; this is predicted to create a frameshift
      p.(His358Alafs*12). Secondly, a deep intronic mutation c.2561-2057A>G caused an
      inframe insertion of 78 intronic bases in the cDNA transcript, leading to a
      premature stop codon p.(Gly854fs*3). The mutations are predicted to cause loss of
      function of PTCH1, consistent with its tumour suppressor function. The findings
      indicate the importance of RNA analysis to detect intronic mutations in PTCH1 not
      identified by routine screening techniques. 

PMID- 24659466
TI  - Bone density testing: science, the media, and patient care.
AB  - Dual-energy X-ray absorptiometry (DXA) is an inexpensive, noninvasive, widely
      available method for diagnosing osteoporosis, assessing fracture risk, and
      monitoring the effects of therapy. By diagnosing high-risk patients before a
      fracture occurs, clinicians can intervene early to reduce fracture risk.
      Appropriate use of DXA results in money saving for healthcare systems that might
      otherwise be spent for fracture-related care. Recent reports of studies
      evaluating DXA screening criteria and intervals for retesting have received
      considerable media coverage, sometimes suggesting that DXA is expensive, over
      utilized, and unnecessary. This may lead to more patients who might benefit from
      early detection of osteoporosis remaining undiagnosed. We advocate for the use of
      current clinical practice guidelines with individualization of patient care
      factors to determine the optimal intervals for DXA testing.

PMID- 24659467
TI  - Prenatally detected de novo apparently balanced chromosomal rearrangements: the
      effect on maternal worry, family functioning and intent of disclosure.
AB  - OBJECTIVE: This study aims to assess the impact of prenatal diagnosis of de novo
      apparently balanced chromosome rearrangements (ABCRs) on maternal stress, family
      functioning and maternal plans of disclosure of genetic information to their
      child. METHODS: All liveborn children with prenatally detected de novo ABCRs in
      two Australian states over a 10-year period (1994-2003) were retrospectively
      ascertained. Of 39 eligible cases, 16 (41%) participated in the study. Mothers of
      these children completed a questionnaire using standardized measures to assess
      family functioning, parental distress, parent-child interaction and child
      characteristics, with open-ended questions regarding disclosure. RESULTS: The
      majority of mothers appeared to experience normal levels of parenting stress,
      quality of parent-child interaction and healthy family functioning. However, most
      mothers recalled experiencing a significant degree of worry at the time of
      receiving their prenatal test results, and some mothers (4/15) reported receiving
      uncertain or conflicting results. Most mothers (13/15) conveyed an understanding
      of the importance of disclosing this genetic information to their child, and
      12/15 conveyed their intention to make this disclosure. CONCLUSION: Most mothers
      reported normal parenting stress and family functioning, despite experiencing
      significant worry upon receiving results. Some children are at risk of
      nondisclosure of their carrier status.

PMID- 24659468
TI  - Human papillomavirus-16/18 AS04-adjuvanted vaccine (cervarix(r)): a guide to its
      two-dose schedule in girls aged 9-14 years in the EU.
AB  - A two-dose vaccination schedule for the human papillomavirus (HPV)-16/18 AS04
      adjuvanted vaccine is approved for the prevention of premalignant cervical
      lesions and cervical cancer causally related to certain oncogenic HPV types in
      girls aged 9-14 years in countries in the EU and elsewhere. In this patient
      population, the two-dose schedule elicited a high immunogenic response that
      matched that of the three-dose schedule in women aged 15-25 years and, therefore,
      was inferred to provide clinical protection against oncogenic HPV cervical
      infection and, consequently, against precancerous lesions and cervical cancer.

PMID- 24659469
TI  - Conservative treatment of giant uterine artery pseudoaneurysm.

PMID- 24659470
TI  - Experts opinion on the use of normative data for functional capacity evaluation
      in occupational and rehabilitation medicine and disability claims.
AB  - PURPOSE: Application of normative values for functional capacity evaluation (FCE)
      is controversial for the assessment of clients for work ability. The objective of
      this study was to study when clinicians and researchers consider normative values
      of FCE useful or of no use for their purposes. METHODS: A focus group meeting was
      organized among 43 FCE experts working in insurance, occupational and/or
      rehabilitation medicine from eight countries during the first international FCE
      research meeting on October 25th, 2012 in the Netherlands. Participants were
      asked to rate to which degree they agree or disagree with a statement concerning
      their position toward normative values for FCE on a 10 cm VAS ranging from 0
      (completely disagree) to 100 (completely agree) at T0 and T1. Arguments for
      aspects that are useful and of no use for normative values were systematically
      collected during the meeting and afterwards independently clustered by two
      researchers in higher order topics. RESULTS: Baseline opinion of participants on
      their position toward normative values was 49 +/- 29 points. After the meeting,
      mean VAS was 55 +/- 23 (p = 0.07), indicating that participants did not
      significantly change their opinion toward normative values. Based on arguments
      provided by the experts, seven higher order topics were constructed namely
      'Comparison with job demands or treatment goals'; 'Comparison with co-workers
      physical ability'; 'Sincerity of effort'; 'Validity for work ability and return
      to work'; 'Experience of referrer with assessment method'; 'Clinimetrics compared
      to alternative assessment methods or reference values'; and 'Ease of use for
      clinician and stakeholders'. CONCLUSIONS: Although experts state useful aspects
      for the use of normative values of FCE for these assessments, it may also lead to
      over-interpretation of results, leading to dualistic statements concerning work
      ability, with potential harmful consequences for work ability of patients.

PMID- 24659471
TI  - Fitting formula for the injection volume of a gas chromatograph for radio-xenon
      sampling in the lower troposphere.
AB  - GC is usually used for xenon concentration and radon removal in the International
      Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty. In a gas
      chromatograph, the injection volume is defined to calculate the column capacity.
      In this paper, the injection volume was investigated and a fitting formula for
      the injection volume was derived and discussed subsequently. As a consequence,
      the xenon injection volume exponentially decreased with the column temperature
      increased, but exponentially increased as the flow rate increased. 

PMID- 24659472
TI  - Combined antibacterial effects of tissue-tolerable plasma and a modern
      conventional liquid antiseptic on chronic wound treatment.
AB  - Potential antimicrobial effects of sequential applications of tissue-tolerable
      plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride
      (ODC) were investigated. 34 patients with chronic leg ulcers were treated with
      TTP, ODC or a combination of both. The bacterial colonization was measured semi
      quantitatively before and immediately after treatment and changes in the
      microbial strains' compositions before and after antiseptic treatments were
      analyzed. All antiseptic procedures reduced the bacterial counts significantly.
      The sequential application of TTP and ODC displayed the highest antimicrobial
      efficacy. Me combined use of TTP and conventional antiseptics might represent the
      most efficient strategy for antiseptic treatment of chronic wounds.

PMID- 24659473
TI  - Sea-level rise and coastal wetlands.
AB  - This paper seeks to quantify the impact of a1-m sea-level rise on coastal
      wetlands in 86 developing countries and territories. It is found that
      approximately 68 % of coastal wetlands in these countries are at risk. A large
      percentage of this estimated loss is found in Europe and Central Asia, East Asia,
      and the Pacific, as well as in the Middle East and North Africa. A small number
      of countries will be severely affected. China and Vietnam(in East Asia and the
      Pacific), Libya and Egypt (in the Middle East and North Africa), and Romania and
      Ukraine (in Europe and Central Asia) will bear most losses. In economic terms,
      the loss of coastal wetlands is likely to exceed $703 million per year in 2000 US
      dollars.

PMID- 24659474
TI  - Connecting diverse knowledge systems for enhanced ecosystem governance: the
      multiple evidence base approach.
AB  - Indigenous and local knowledge systems as well as practitioners' knowledge can
      provide valid and useful knowledge to enhance our understanding of governance of
      biodiversity and ecosystems for human well-being. There is, therefore, a great
      need within emerging global assessment programs, such as the IPBES and other
      international efforts, to develop functioning mechanisms for legitimate,
      transparent, and constructive ways of creating synergies across knowledge
      systems. We present the multiple evidence base (MEB) as an approach that proposes
      parallels whereby indigenous, local and scientific knowledge systems are viewed
      to generate different manifestations of knowledge, which can generate new
      insights and innovations through complementarities. MEB emphasizes that
      evaluation of knowledge occurs primarily within rather than across knowledge
      systems. MEB on a particular issue creates an enriched picture of understanding,
      for triangulation and joint assessment of knowledge, and a starting point for
      further knowledge generation.

PMID- 24659476
TI  - Inhibition of Akt/mTOR attenuates age-related changes in mesenchymal stem cells.
AB  - The decline in mesenchymal stem cell (MSC) self-renewal and function with aging
      contributes to diseases associated with impaired osteogenesis. MSC donor age in
      prolonged culture also limits the therapeutic potential of these cells for tissue
      engineering and regenerative medicine. Here, we demonstrate an intervention to
      preserve the immature state MSC and consequently maintain self-renewal and
      differentiation capacity during in vitro aging. We showed that blocking of
      phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) prevents
      the development of an age-related phenotype and maintains MSC morphology of early
      passage cells with high clonogenic frequency and enhanced proliferative capacity.
      MSC cultured in the presence of inhibitors of Akt or mTOR also robustly maintain
      their osteogenic potential, that is otherwise lost during in vitro aging. We
      further report that these effects may be mediated by induction of expression of
      pluripotency genes Nanog and Oct-4 and by the reduction in the production of
      cytoplasmic reactive oxygen species (ROS). Additionally, loss of Akt/mTOR and ROS
      was accompanied with lower levels of DNA damage. These results provide an insight
      into mechanisms involved in MSC aging and suggest possible interventions to
      maintain quiescence and function of MSC prior to in vivo transplantation or as
      pharmacological agents in diseases associated with loss of MSC function.

PMID- 24659477
TI  - ETS fusion genes in prostate cancer.
AB  - Prostate cancer is very common in elderly men in developed countries. Unravelling
      the molecular and biological processes that contribute to tumor development and
      progressive growth, including its heterogeneity, is a challenging task. The
      fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in
      prostate cancer. ERG is an oncogene that encodes a member of the family of ETS
      transcription factors. At lower frequency, other members of this gene family are
      also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen
      regulated gene that is preferentially expressed in the prostate. Most of the less
      frequent ETS fusion partners are also androgen-regulated and prostate-specific.
      During the last few years, novel concepts of the process of gene fusion have
      emerged, and initial experimental results explaining the function of the ETS
      genes ERG and ETV1 in prostate cancer have been published. In this review, we
      focus on the most relevant ETS gene fusions and summarize the current knowledge
      of the role of ETS transcription factors in prostate cancer. Finally, we discuss
      the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate
      cancer. 

PMID- 24659478
TI  - Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer.
AB  - Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless,
      the medicine has continued to surprise us, perform, and save lives for the past
      40 years. Unlike any other medicine in oncology, it is used to treat all stages
      of breast cancer, ductal carcinoma in situ, and male breast cancer and pioneered
      the use of chemoprevention by reducing the incidence of breast cancer in women at
      high risk and induces ovulation in subfertile women! The impact of tamoxifen is
      ubiquitous. However, the power to save lives from this unlikely success story
      came from the first laboratory studies which defined that 'longer was going to be
      better' when tamoxifen was being considered as an adjuvant therapy. This is that
      success story, with a focus on the interdependent components of: excellence in
      drug discovery, investment in self-selecting young investigators, a conversation
      with Nature, a conversation between the laboratory and the clinic, and the
      creation of the Oxford Overview Analysis. Each of these factors was essential to
      propel the progress of tamoxifen to evolve as an essential part of the fabric of
      society. 

PMID- 24659479
TI  - Upregulation of glucose metabolism by NF-kappaB2/p52 mediates enzalutamide
      resistance in castration-resistant prostate cancer cells.
AB  - Cancer cells reprogram their metabolic pathways to facilitate fast proliferation.
      Previous studies have shown that overexpression of NF-kappaB2/p52 (p52) in
      prostate cancer cells promotes cell growth and leads to castration resistance
      through aberrant activation of androgen receptor (AR). In addition, these cells
      become resistant to enzalutamide. In this study, we investigated the effects of
      p52 activation on glucose metabolism and on response to enzalutamide therapy.
      Data analysis of gene expression arrays showed that genes including GLUT1
      (SLC2A1), PKM2, G6PD, and ME1 involved in the regulation of glucose metabolism
      were altered in LNCaP cells overexpressing p52 compared with the parental LNCaP
      cells. We demonstrated an increased amount of glucose flux in the glycolysis
      pathway, as well as the pentose phosphate pathway (PPP) upon p52 activation. The
      p52-overexpressing cells increase glucose uptake and are capable of higher ATP
      and lactate production compared with the parental LNCaP cells. The growth of p52
      overexpressing cells depends on glucose in the culture media and is sensitive to
      glucose deprivation compared with the parental LNCaP cells. Targeting glucose
      metabolism by the glucose analog 2-deoxy-d-glucose synergistically inhibits cell
      growth when combined with enzalutamide, and resensitizes p52-overexpressing cells
      to enzalutamide treatment. These results suggest that p52 modulates glucose
      metabolism, enhances glucose flux to glycolysis and PPPs, thus facilitating fast
      proliferation of the cells. Co-targeting glucose metabolism together with AR axis
      synergistically inhibits cell growth and restores enzalutamide-resistant cells to
      enzalutamide treatment. 

PMID- 24659481
TI  - Clinicopathological study of SDHB mutation-related pheochromocytoma and
      sympathetic paraganglioma.

PMID- 24659483
TI  - Recent advances on plasmin inhibitors for the treatment of fibrinolysis-related
      disorders.
AB  - Growing evidence suggests that plasmin is involved in a number of physiological
      processes in addition to its key role in fibrin cleavage. Plasmin inhibition is
      critical in preventing adverse consequences arising from plasmin overactivity,
      e.g., blood loss that may follow cardiac surgery. Aprotinin was widely used as an
      antifibrinolytic drug before its discontinuation in 2008. Tranexamic acid and
      epsilon-aminocaproic acid, two small molecule plasmin inhibitors, are currently
      used in the clinic. Several molecules have been designed utilizing covalent, but
      reversible, chemistry relying on reactive cyclohexanones, nitrile warheads, and
      reactive aldehyde peptidomimetics. Other major classes of plasmin inhibitors
      include the cyclic peptidomimetics and polypeptides of the Kunitz and Kazal-type.
      Allosteric inhibitors of plasmin have also been designed including small molecule
      lysine analogs that bind to plasmin's kringle domain(s) and sulfated
      glycosaminoglycan mimetics that bind to plasmin's catalytic domain. Plasmin
      inhibitors have also been explored for resolving other disease states including
      cell metastasis, cell proliferation, angiogenesis, and embryo implantation. This
      review highlights functional and structural aspects of plasmin inhibitors with
      the goal of advancing their design. 

PMID- 24659480
TI  - The ubiquitin-proteasome system: opportunities for therapeutic intervention in
      solid tumors.
AB  - The destruction of proteins via the ubiquitin-proteasome system is a multi-step,
      complex process involving polyubiquitination of substrate proteins, followed by
      proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors
      of the proteasome promote the accumulation of proteins that are deleterious to
      cell survival, and represent promising anti-cancer agents. In multiple myeloma
      and mantle cell lymphoma, treatment with the first-generation proteasome
      inhibitor, bortezomib, or the second-generation inhibitor, carfilzomib, has
      demonstrated significant therapeutic benefit in humans. This has prompted United
      States Food and Drug Administration (US FDA) approval of these agents and
      development of additional second-generation compounds with improved properties.
      There is considerable interest in extending the benefits of proteasome inhibitors
      to the treatment of solid tumor malignancies. Herein, we review progress that has
      been made in the preclinical development and clinical evaluation of different
      proteasome inhibitors in solid tumors. In addition, we describe several novel
      approaches that are currently being pursued for the treatment of solid tumors,
      including drug combinatorial strategies incorporating proteasome inhibitors and
      the targeting of components of the ubiquitin-proteasome system that are distinct
      from the 26S proteasome complex. 

PMID- 24659484
TI  - Serum leptin is associated with metabolic syndrome in obese Mexican subjects.
AB  - BACKGROUND: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities
      including insulin resistance, dyslipidemia, high blood pressure, and abdominal
      adiposity. Obese patients develop leptin resistance, and an increased waist
      circumference (WC) due to deposition of abdominal fat. The aim of this study was
      to evaluate the association between circulating leptin levels and MetS among
      sample adult Mexican workers. METHOD: A total of 204 workers aged 20-56 were
      evaluated. Anthropometric index, blood pressure, fasting plasma glucose, and
      lipid profile were measured by spectrophotometric methods. Fasting insulin and
      leptin were measured by inmunoenzimatic methods. Furthermore, homeostasis model
      assessment for insulin resistance (HOMA-IR) was calculated. RESULTS: The
      prevalence of MetS according to the ATP-III criteria was 33.8% and leptin
      concentrations were 2.5 times higher in women than men. Subjects with MetS had
      higher levels of leptin (26.7 +/- 13.7) compared with those without MetS (20.1 +/
      13.9; P <0.001). Leptin increased significantly while BMI increased as well
      (normal 14.0 +/- 8.9, overweight 22.7 +/- 11.7 and obese 31.4 +/- 14.6) in
      addition to other variables such as WC, HDL-C, insulin levels, and HOMA index.
      Each component of MetS was stratified by sex and submitted by linear regression
      with a 95% of accuracy. The 50% and 53% of the BMI is explained by the
      concentration of leptin in men and women, respectively (P < 0.001). CONCLUSION:
      This study found that leptin was associated with the MetS, especially in obesity
      and insulin resistance, indicating a high risk for university workers to develop
      hypertension, DM2, and cardiovascular disease.

PMID- 24659482
TI  - Select aging biomarkers based on telomere length and chronological age to build a
      biological age equation.
AB  - The purpose of this study is to build a biological age (BA) equation combining
      telomere length with chronological age (CA) and associated aging biomarkers. In
      total, 139 healthy volunteers were recruited from a Chinese Han cohort in
      Beijing. A genetic index, renal function indices, cardiovascular function
      indices, brain function indices, and oxidative stress and inflammation indices (C
      reactive protein [CRP]) were measured and analyzed. A BA equation was proposed
      based on selected parameters, with terminal telomere restriction fragment (TRF)
      and CA as the two principal components. The selected aging markers included
      mitral annulus peak E anterior wall (MVEA), intima-media thickness (IMT),
      cystatin C (CYSC), D-dimer (DD), and digital symbol test (DST). The BA equation
      was: BA = -2.281TRF + 26.321CYSC + 0.025DD - 104.419MVEA + 34.863IMT - 0.265DST +
      0.305CA + 26.346. To conclude, telomere length and CA as double benchmarks may be
      a new method to build a BA.

PMID- 24659485
TI  - Bundle sheath suberization in grass leaves: multiple barriers to
      characterization.
AB  - High-yielding, stress-tolerant grass crops are essential to meet future food and
      energy demands. Efforts are underway to engineer improved varieties of the C3
      cereal crop rice by introducing NADP-malic enzyme C4 photosynthesis using maize
      as a model system. However, several modifications to the rice leaf vasculature
      are potentially necessary, including the introduction of suberin lamellae into
      the bundle sheath cell walls. Suberized cell walls are ubiquitous in the root
      endodermis of all grasses, and developmental similarities are apparent between
      endodermis and bundle sheath cell walls. Nonetheless, there is considerable
      heterogeneity in sheath cell development and suberin composition both within and
      between grass taxa. The effect of this variation on physiological function
      remains ambiguous over forty years after suberin lamellae were initially proposed
      to regulate solute and photoassimilate fluxes and C4 gas exchange. Interspecies
      variation has confounded efforts to ascribe physiological differences
      specifically to the presence or absence of suberin lamellae. Thus, specific
      perturbation of suberization within a uniform genetic background is needed, but,
      until recently, the genetic resources to manipulate suberin composition in the
      grasses were largely unavailable. The recent dissection of the suberin
      biosynthesis pathway in model dicots and the identification of several promising
      candidate genes in model grasses will facilitate the characterization of the
      first suberin biosynthesis genes in a monocot. Much remains to be learned about
      the role of bundle sheath suberization in leaf physiology, but the stage is set
      for significant advances in the near future. 

PMID- 24659486
TI  - Redox activity of thioredoxin z and fructokinase-like protein 1 is dispensable
      for autotrophic growth of Arabidopsis thaliana.
AB  - Redox modulation of protein activity by thioredoxins (TRXs) plays a key role in
      cellular regulation. Thioredoxin z (TRX z) and its interaction partner
      fructokinase-like protein 1 (FLN1) represent subunits of the plastid-encoded RNA
      polymerase (PEP), suggesting a role of both proteins in redox regulation of
      chloroplast gene expression. Loss of TRX z or FLN1 expression generates a PEP
      deficient phenotype and renders the plants incapable to grow autotrophically.
      This study shows that PEP function in trx z and fln1 plants can be restored by
      complementation with redox-inactive TRX z C106S and FLN1 C105/106A protein
      variants, respectively. The complemented plants showed wild-type levels of
      chloroplast gene expression and were restored in photosynthetic capacity,
      indicating that redox regulation of PEP through TRX z/FLN1 per se is not
      essential for autotrophic growth. Promoter-reporter gene studies indicate that
      TRX z and FLN1 are expressed during early phases of leaf development while
      expression ceases at maturation. Taken together, our data support a model in
      which TRX z and FLN1 are essential structural components of the PEP complex and
      their redox activity might only play a role in the fine tuning of PEP function. 

PMID- 24659487
TI  - Transcriptional and hormonal regulation of petal and stamen development by
      STAMENLESS, the tomato (Solanum lycopersicum L.) orthologue to the B-class
      APETALA3 gene.
AB  - Four B-class MADS box genes specify petal and stamen organ identities in tomato.
      Several homeotic mutants affected in petal and stamen development were described
      in this model species, although the causal mutations have not been identified for
      most of them. In this study we characterized a strong stamenless mutant in the
      tomato Primabel cultivar (sl-Pr), which exhibited homeotic conversion of petals
      into sepals and stamens into carpels and we compared it with the stamenless
      mutant in the LA0269 accession (sl-LA0269). Genetic complementation analysis
      proved that both sl mutants were allelic. Sequencing revealed point mutations in
      the coding sequence of the Tomato APETALA3 (TAP3) gene of the sl-Pr genome, which
      lead to a truncated protein, whereas a chromosomal rearrangement in the TAP3
      promoter was detected in the sl-LA0269 allele. Moreover, the floral phenotype of
      TAP3 antisense plants exhibited identical homeotic changes to sl mutants. These
      results demonstrate that SL is the tomato AP3 orthologue and that the mutant
      phenotype correlated to the SL silencing level. Expression analyses showed that
      the sl-Pr mutation does not affect the expression of other tomato B-class genes,
      although SL may repress the A-class gene MACROCALYX. A partial reversion of the
      sl phenotype by gibberellins, gene expression analysis, and hormone
      quantification in sl flowers revealed a role of phytohormones in flower
      development downstream of the SL gene. Together, our results indicated that petal
      and stamen identity in tomato depends on gene-hormone interactions, as mediated
      by the SL gene. 

PMID- 24659488
TI  - Gene regulatory cascade of senescence-associated NAC transcription factors
      activated by ETHYLENE-INSENSITIVE2-mediated leaf senescence signalling in
      Arabidopsis.
AB  - Leaf senescence is a finely tuned and genetically programmed degeneration
      process, which is critical to maximize plant fitness by remobilizing nutrients
      from senescing leaves to newly developing organs. Leaf senescence is a complex
      process that is driven by extensive reprogramming of global gene expression in a
      highly coordinated manner. Understanding how gene regulatory networks involved in
      controlling leaf senescence are organized and operated is essential to decipher
      the mechanisms of leaf senescence. It was previously reported that the trifurcate
      feed-forward pathway involving EIN2, ORE1, and miR164 in Arabidopsis regulates
      age-dependent leaf senescence and cell death. Here, new components of this
      pathway have been identified, which enhances knowledge of the gene regulatory
      networks governing leaf senescence. Comparative gene expression analysis revealed
      six senescence-associated NAC transcription factors (TFs) (ANAC019, AtNAP,
      ANAC047, ANAC055, ORS1, and ORE1) as candidate downstream components of ETHYLENE
      INSENSITIVE2 (EIN2). EIN3, a downstream signalling molecule of EIN2, directly
      bound the ORE1 and AtNAP promoters and induced their transcription. This suggests
      that EIN3 positively regulates leaf senescence by activating ORE1 and AtNAP,
      previously reported as key regulators of leaf senescence. Genetic and gene
      expression analyses in the ore1 atnap double mutant revealed that ORE1 and AtNAP
      act in distinct and overlapping signalling pathways. Transient transactivation
      assays further demonstrated that ORE1 and AtNAP could activate common as well as
      differential NAC TF targets. Collectively, the data provide insight into an EIN2
      mediated senescence signalling pathway that coordinates global gene expression
      during leaf senescence via a gene regulatory network involving EIN3 and
      senescence-associated NAC TFs. 

PMID- 24659490
TI  - Prospective analysis of infectious disease surveillance data using syndromic
      information.
AB  - In this paper, we describe a Bayesian hierarchical Poisson model for the
      prospective analysis of data for infectious diseases. The proposed model consists
      of two components. The first component describes the behavior of disease during
      nonepidemic periods and the second component represents the increase in disease
      counts due to the presence of an epidemic. A novelty of our model formulation is
      that the parameters describing the spread of epidemics are allowed to vary in
      both space and time. We also show how syndromic information can be incorporated
      into the model to provide a better description of the data and more accurate one
      step-ahead forecasts. These real-time forecasts can be used to identify high-risk
      areas for outbreaks and, consequently, to develop efficient targeted
      surveillance. We apply the methodology to weekly emergency room discharges for
      acute bronchitis in South Carolina.

PMID- 24659489
TI  - The transcription factor AREB1 regulates primary metabolic pathways in tomato
      fruits.
AB  - Tomato fruit development is regulated both by the action of plant hormones and by
      tight genetic control. Recent studies suggest that abscisic acid (ABA) signalling
      may affect different aspects of fruit maturation. Previously, it was shown that
      SlAREB1, an ABA-regulated transcription factor involved in stress-induced
      responses, is expressed in seeds and in fruit tissues in tomato. Here, the role
      of SlAREB1 in regulating the expression of genes relevant for primary metabolic
      pathways and affecting the metabolic profile of the fruit was investigated using
      transgenic tomato lines. Metabolite profiling using gas chromatography-time of
      flight mass spectrometry (GC-TOF-MS) and non-targeted liquid chromatography-mass
      spectrometry (LC-MS) was performed on pericarp tissue from fruits harvested at
      three stages of fruit development. Principal component analysis of the data could
      distinguish the metabolite profiles of non-transgenic fruits from those that
      overexpress and down-regulate SlAREB1. Overexpression of SlAREB1 resulted in
      increased content of organic acids, hexoses, hexose-phosphates, and amino acids
      in immature green, mature green, and red ripe fruits, and these modifications
      correlated with the up-regulation of enzyme-encoding genes involved in primary
      carbohydrate and amino acid metabolism. A non-targeted LC-MS analysis indicated
      that the composition of secondary metabolites is also affected in transgenic
      lines. In addition, gene expression data revealed that some genes associated with
      fruit ripening are also up-regulated in SlAREB1-overexpressing lines compared
      with wild-type and antisense lines. Taken together, the results suggest that
      SlAREB1 participates in the regulation of the metabolic programming that takes
      place during fruit ripening and that may explain part of the role of ABA in fruit
      development in tomato. 

PMID- 24659491
TI  - Evaluation of cluster recovery for small area relative risk models.
AB  - The analysis of disease risk is often considered via relative risk. The
      comparison of relative risk estimation methods with "true risk" scenarios has
      been considered on various occasions. However, there has been little examination
      of how well competing methods perform when the focus is clustering of risk. In
      this paper, a simulated evaluation of a range of potential spatial risk models
      and a range of measures that can be used for (a) cluster goodness of fit, (b)
      cluster diagnostics are considered. Results suggest that exceedence probability
      is a poor measure of hot spot clustering because of model dependence, whereas
      residual-based methods are less model dependent and perform better. Local
      deviance information criteria measures perform well, but conditional predictive
      ordinate measures yield a high false positive rate.

PMID- 24659492
TI  - Detecting the violation of variance homogeneity in mixed models.
AB  - Mixed-effects models are increasingly used in many areas of applied science.
      Despite their popularity, there is virtually no systematic approach for examining
      the homogeneity of the random-effects covariance structure commonly assumed for
      such models. We propose two tests for evaluating the homogeneity of the
      covariance structure assumption across subjects: one is based on the covariance
      matrices computed from the fitted model and the other is based on the empirical
      variation computed from the estimated random effects. We used simulation studies
      to compare performances of the two tests for detecting violations of the
      homogeneity assumption in the mixed-effects models and showed that they were able
      to identify abnormal clusters of subjects with dissimilar random-effects
      covariance structures; in particular, their removal from the fitted model might
      change the signs and the magnitudes of important predictors in the analysis. In a
      case study, we applied our proposed tests to a longitudinal cohort study of
      rheumatoid arthritis patients and compared their abilities to ascertain whether
      the assumption of covariance homogeneity for subject-specific random effects
      holds.

PMID- 24659493
TI  - Alleviation of podocyte injury: the possible pathway implicated in anti
      inflammation of alpha-lipoic acid in type 2 diabetics.
AB  - BACKGROUND AND AIMS: The objective of this study is to observe the effect of
      alpha-lipoic acid (ALA) on Pod injury by anti-inflammation and explore its
      possible renal protective mechanism. METHODS: A total of 36 cases with type 2
      diabetes with microalbuminuria and fasting plasma glucose (FPG) levels less than
      9 mmol/L and glycated hemoglobin A1c (HbA1c) <=9.0 % were recruited to be treated
      with ALA (600 mg, daily) for 6 months (group DA). Another 30 healthy individuals
      were chosen as normal controls (group NC). The levels of serum creatinine (Cr),
      FPG, and HbA1c were detected; blood pressure was recorded; and early morning
      urine samples (corrected for urinary Cr) were collected for the examination of
      urinary monocyte chemoattractant protein-1 (MCP-1), transforming growth factor
      beta1 (TGF-beta1), podocalyxin (PCX), nephrin, albumin and Cr in group NC and
      group DA at the baseline and the sixth month. RESULTS: The excretions of urinary
      MCP-1, TGF-beta1, PCX, nephrin and albumin to Cr ratio (abbreviated as UMCR,
      UTCR, UPCR, UNCR and UACR respectively) were significantly increased in group DA
      compared with group NC (all P < 0.01), and after 6-month treatment, all indexes
      mentioned above decreased markedly (P < 0.05), while FPG and HbA1c had no obvious
      changes. Additionally, there was a positive correlation between UMCR, UTCR with
      UPCR, UNCR and UACR, respectively (all P < 0.01). CONCLUSIONS: Anti-inflammation
      of ALA in vivo and local kidney is implicated in the protection of glomerular Pod
      injury in patients with type 2 diabetes.

PMID- 24659497
TI  - Allelic expression analysis in the brain suggests a role for heterogeneous
      insults affecting epigenetic processes in autism spectrum disorders.
AB  - Monoallelic expression, including genomic imprinting, X-chromosome inactivation
      and random monoallelic expression of autosomal genes are epigenetic phenomena.
      Genes that are expressed in a monoallelic way may be more vulnerable to genetic
      or epigenetic mutations. Thus, comprehensive exploration of monoallelic
      expression in human brains may shed light on complex brain disorders. Autism
      related disorders are known to be associated with imprinted genes on chromosome
      15. However, it is not clear whether other imprinted regions or other types of
      monoallelic expression are associated with autism spectrum disorder (ASD). Here,
      we performed a genome-wide survey of allele expression imbalance (AEI) in the
      human brain using single-nucleotide polymorphisms (SNPs), in 18 individuals with
      ASD and 15 controls. Individuals with ASD had the most extreme number of
      monoallelic expressed SNPs in both the autosomes and the X chromosome. In two
      cases that were studied in detail, the monoallelic expression was confined to
      specific brain region or cell type. Using these data, we were also able to define
      the allelic expression status of known imprinted genes in the human brain and to
      identify abnormal imprinting in an individual with ASD. Lastly, we developed an
      analysis of individual-level expression, focusing on the difference of each
      individual from the mean. We found that individuals with ASD had more genes that
      were up- or down-regulated in an individual-specific manner. We also identified
      pathways perturbed in specific individuals. These results underline the
      heterogeneity in gene regulation in ASD, at the level of both allelic and total
      expression. 

PMID- 24659496
TI  - Nuclear protein spreading: implication for pathophysiology of neuromuscular
      diseases.
AB  - While transfer of a protein encoded by a single nucleus to nearby nuclei in
      multinucleated cells has been known for almost 25 years, the biological
      consequences for gain-of-function diseases have not been considered. Here, we
      have investigated nuclear protein spreading and its potential consequences in two
      of the three most prevalent neuromuscular diseases. By performing co-cultures
      between diseased or control human myoblasts and murine C2C12 myoblasts, we
      demonstrate that in facioscapulohumeral dystrophy, although the transcription of
      the toxic protein DUX4 occurs in only a limited number of nuclei, the resulting
      protein diffuses into nearby nuclei within the myotubes, thus spreading aberrant
      gene expression. In myotonic dystrophy type 1, we observed that in human-mouse
      heterokaryons, the expression of a mutated DMPK from human nuclei titrates
      splicing factors produced by neighboring nuclei, inducing the mis-splicing of
      several pre-mRNAs in murine nuclei. In both cases, the spreading of the
      pathological phenotypes from one nucleus to another is observed, highlighting an
      additional mechanism that contributes to the dissemination and worsening of the
      muscle pathogenesis. These results indicate that nuclear protein spreading may be
      an important component of pathophysiology of gain of function muscular diseases
      which should be taken into consideration in the design of new therapeutic
      approaches. 

PMID- 24659498
TI  - Dystrophic mdx mice develop severe cardiac and respiratory dysfunction following
      genetic ablation of the anti-inflammatory cytokine IL-10.
AB  - Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease that
      causes respiratory and cardiac failure. Inflammation is a key pathological
      characteristic of dystrophic muscle lesion formation, but its role and regulation
      in the disease time course has not been sufficiently examined. In the present
      study, we used IL-10(-/-)/mdx mice lacking both dystrophin and the anti
      inflammatory cytokine, interleukin-10 (IL-10), to investigate whether a
      predisposition to inflammation affects the severity of DMD with advancing age.
      The IL-10 deficiency caused a profound DMD phenotype in the dystrophic heart such
      as muscle degeneration and extensive myofiber loss, but the limb muscle and
      diaphragm morphology of IL-10(-/) (-)/mdx mice was similar to that of mdx mice.
      Extensive infiltrates of pro-inflammatory M1 macrophages in regeneration of
      cardiotoxin-injured muscle, altered M1/M2 macrophage phenotype and increased pro
      inflammatory cytokines/chemokines production were observed in the diaphragm and
      heart of IL-10(-/-)/mdx mice. We characterized the IL-10(-/-)/mdx mice as a
      dystrophic model with chronic inflammation and severe cardiorespiratory
      dysfunction, as evidenced by decreased percent fractional shortening (%FS) and
      ejection fraction percent (EF%) on echocardiography, reduced lower tidal volume
      on whole-body plethysmography. This study suggests that a predisposition to
      inflammation is an important indicator of DMD disease progression. Therefore, the
      development of anti-inflammatory strategies may help in slowing down the
      cardiorespiratory dysfunction on DMD. 

PMID- 24659499
TI  - jmzTab: a java interface to the mzTab data standard.
AB  - mzTab is the most recent standard format developed by the Proteomics Standards
      Initiative. mzTab is a flexible tab-delimited file that can capture
      identification and quantification results coming from MS-based proteomics and
      metabolomics approaches. We here present an open-source Java application
      programming interface for mzTab called jmzTab. The software allows the efficient
      processing of mzTab files, providing read and write capabilities, and is designed
      to be embedded in other software packages. The second key feature of the jmzTab
      model is that it provides a flexible framework to maintain the logical integrity
      between the metadata and the table-based sections in the mzTab files. In this
      article, as two example implementations, we also describe two stand-alone tools
      that can be used to validate mzTab files and to convert PRIDE XML files to mzTab.
      The library is freely available at http://mztab.googlecode.com.

PMID- 24659500
TI  - In silico study of the structurally similar ORL1 receptor agonist and antagonist
      pairs reveal possible mechanism of receptor activation.
AB  - An opioid receptor like (ORL1) receptor is a member of a family of G-protein
      coupled receptors. It is anew pharmaceutical target with broad therapeutic
      potential in the regulation of important biological functions such as
      nociception, mood disorders, drug abuse, learning or cardiovascular control. The
      crystal structure of this receptor in complex with an antagonist was determined
      recently (PDBID: 4EA3). By removing the ligand and subjecting the empty receptor
      to molecular dynamics simulation in a solvated lipid membrane we obtained an
      optimized ORL1 receptor structure which could be used in a subsequent docking
      study of two structurally similar agonist-antagonist ligand pairs. Ligands were
      docked to the empty ORL1 receptor (with and without the third intracellular loop,
      IC3)in different orientations, and the resulting complexes were monitored during
      molecular dynamics simulation in order to see how the subtle differences in
      structure of agonists and antagonists might affect ligand-receptor interactions
      and trigger receptor activation. It was established that agonists and antagonists
      bound to the same, relatively large, binding site in the receptor, created by
      residues from transmembrane helices TM2, TM3, TM5, TM6 and TM7 and close to the
      extra cellular end of the receptor bundle.The key difference between these two
      types of ligands is interaction with residue Val283(6.55) and a flexibility of
      ligand molecules. Ligands that cannot easily avoid this interaction will initiate
      movement of the intracellular end of TM6 (by a mechanism which involves
      Met134(3.36) and several amino acids of TM5) and possibly activate the receptor
      when assisted by G-protein.

PMID- 24659501
TI  - Laparoscopic vs. open surgery for treating benign liver lesions: assessing
      quality of life in the first year after surgery.
AB  - Laparoscopic liver surgery has not yet gained widespread acceptance among liver
      surgeons. Some questions remain regarding indications to surgery and health
      related quality of life (HRQOL) after surgery, especially for the treatment of
      benign lesions, has so far not yet been investigated. The aim of this study is to
      evaluate HRQOL at 1 month, 6 months and 1 year after surgery in two groups of
      patients undergoing liver resections for benign liver lesions either by
      laparoscopic or open surgery. From January 2004 to September 2010 75 patients
      underwent surgery (29 laparoscopic, 46 open) for benign liver lesions.We
      retrospectively compared surgical results of the two groups and evaluated HRQOL
      with the SF-36 test. A personal or telephonic interview was administrated for the
      assessment of HRQOL before surgical treatment and at1 month, 6 months and 1 year
      after surgery. Sixty six patients (88%) were available for the study. The length
      of stay (4.7 vs. 8.2 days, p = 0.0002), the reprisal of oral intake (II post-op
      vs. III post-op, p = 0.02) the number of transfused patients (2 vs. 8, p = 0.1)
      and the overall rate of morbidity (p = 0.06) were lower in the laparoscopic
      group.HRQOL was significantly better in the laparoscopic group in the first year
      after surgery. Surgical treatment for benign liver lesions, when indicated,
      should be laparoscopic. This approach shows a lower rate of surgical
      complications with a better quality of life after surgery and a faster reprisal
      of social and job activities.

PMID- 24659502
TI  - Sonographic diagnosis of abscess following breast-conserving surgery with
      insertion of nonabsorbable mesh.
AB  - Immediate mesh insertion has been recently used for breast reconstruction after
      breast-conserving surgery. We report a case of abscess formation following
      immediate nonabsorbable mesh insertion with breast-conserving surgery. In this
      article, we demonstrate multimodal breast imaging features and pathologic
      correlations of the case. In addition, we illustrate characteristic sonographic
      findings of nonabsorbable mesh fibers to differentiate them from a gossypiboma
      caused by a retained surgical sponge or tumor recurrence.

PMID- 24659503
TI  - Built environment characteristics and parent active transportation are associated
      with active travel to school in youth age 12-15.
AB  - PURPOSE: To investigate the relation of factors from multiple levels of
      ecological models (ie, individual, interpersonal and environmental) to active
      travel to/from school in an observational study of young adolescents. METHODS:
      Participants were 294 12-15-year olds living within two miles of their school.
      Demographic, psychosocial and perceived built environment characteristics around
      the home were measured by survey, and objective built environment factors around
      home and school were assessed in Geographic Information Systems (GIS). Mixed
      effects multinomial regression models tested correlates of engaging in 1-4 (vs 0)
      and 5-10 (vs 0) active trips/week to/from school, adjusted for distance and other
      covariates. RESULTS: 64% of participants reported >=1 active trip/week to/from
      school. Significant correlates of occasional and/or habitual active travel
      to/from school included barriers (ORs=0.27 and 0.15), parent modelling of active
      travel (OR=3.27 for habitual), perceived street connectivity (OR=1.78 for
      occasional), perceived pedestrian safety around home (OR=2.04 for habitual),
      objective street connectivity around home (OR=0.97 for occasional), objective
      residential density around home (ORs=1.10 and 1.11) and objective residential
      density around school (OR=1.14 for habitual). Parent modelling interacted with
      pedestrian safety in explaining active travel to/from school. CONCLUSIONS:
      Results supported multilevel correlates of adolescents' active travel to school,
      consistent with ecological models. Correlates of occasional and habitual active
      travel to/from school were similar. Built environment attributes around schools,
      particularly residential density, should be considered when siting new schools
      and redeveloping neighbourhoods around existing schools.

PMID- 24659504
TI  - Epidemiology of concussion in men's elite Rugby-7s (Sevens World Series) and
      Rugby-15s (Rugby World Cup, Junior World Championship and Rugby Trophy, Pacific
      Nations Cup and English Premiership).
AB  - OBJECTIVE: To determine the incidence, nature and causes of concussions sustained
      during men's elite professional Rugby-7s and Rugby-15s. DESIGN: A prospective
      cohort study recording injuries classified as a time-loss concussion. POPULATION:
      Players competing in the following tournaments: Rugby 15s-English Premiership
      (2007/2008 to 2010/2011), Rugby World Cup (2007, 2011), Pacific Nations Cup
      (2012, 2013), Junior World Championship (2008, 2010-2013), Junior World Rugby
      Trophy (2008, 2010-2013); Rugby 7s-Sevens World Series (2008/2009, 2010/2011 to
      2012/2013). METHOD: The study was implemented according to the international
      consensus statement for epidemiological studies in rugby union; the main outcome
      measures included the number, incidence (number of concussions/1000 player-match
      hours), mean and median severity (days absence) and cause of concussion. RESULTS:
      The incidence of concussion in Rugby-7s was significantly higher than that in
      Rugby-15s (risk ratio=1.84; p<0.001). The severity of concussions were
      significantly higher in Rugby-7s than Rugby-15s (mean-Rugby-7s: 19.2, Rugby-15s:
      10.1; median-Rugby 7s: 20, Rugby-15s: 7; p<0.001). The main causes of concussion
      were tackling (44.1%) in Rugby-7s and collisions (43.6%) in Rugby-15s.
      Significantly more (risk ratio=1.49; p=0.004) concussed players were removed
      immediately from the game in Rugby-7s (69.7%) compared to Rugby-15s (46.7%).
      CONCLUSIONS: Six actions were identified to improve the management of concussion
      in rugby: implement a pitch-side concussion assessment protocol; improve
      compliance with return-to-play protocols; work with referees to review the nature
      and consequences of collisions; improve players' tackle technique; investigate
      the forces involved in tackles and collisions; and evaluate reasons for the
      higher incidence of concussions in Rugby-7s.

PMID- 24659505
TI  - Hip chondropathy at arthroscopy: prevalence and relationship to labral pathology,
      femoroacetabular impingement and patient-reported outcomes.
AB  - BACKGROUND: This study aimed to describe chondropathy prevalence in adults who
      had undergone hip arthroscopy for hip pain. The relationships between
      chondropathy severity and (1) participant characteristics; and (2) patient
      reported outcomes (PROs) at initial assessment (~18 months postsurgery) and over
      a further 12 months (~30 months postsurgery) were evaluated. Finally, the
      relationships between chondropathy and coexisting femoroacetabular impingement
      (FAI) and labral pathology at the time of surgery were evaluated. METHODS: 100
      consecutive patients (36+/-12 years) who underwent hip arthroscopy 18 months
      previously participated. Hip Osteoarthritis and Disability Outcome Score (HOOS)
      and International Hip Outcome Tool (iHOT-33) data were collected prospectively at
      18 months postsurgery and at 30 months postsurgery. Surgical data were collected
      retrospectively. Participants were grouped: Outerbridge grade 0, no chondropathy;
      Outerbridge grade I-II, mild chondropathy; Outerbridge III-IV, severe
      chondropathy. The presence of FAI or labral pathology was noted. RESULTS: The
      prevalence of chondropathy (>=grade I) at hip arthroscopy was 72%. Participants
      with severe chondropathy were significantly worse for all HOOS subscales and the
      iHOT-33 at 18 months postsurgery (HOOS-symptoms (p=0.017); HOOS-pain (p=0.024);
      HOOS-activity (p=0.009); HOOS-sport (p=0.004); HOOS-quality-of-life (p=0.006);
      iHOT-33 (p=0.013)) than those with no chondropathy. At 12-month follow-up, HOOS
      quality-of-life in those without chondropathy was the only PRO that improved.
      Relative risk of coexisting chondropathy with labral pathology or FAI was 40%.
      CONCLUSIONS: Chondropathy was prevalent, and associated with increasing age,
      coexisting labral pathology or FAI. Severe chondropathy was associated with worse
      pain and function at 18 months postsurgery. Little improvements were observed in
      participants over a further 12 months, regardless of chondropathy status.

PMID- 24659506
TI  - Monitoring of biological markers indicative of doping: the athlete biological
      passport.
AB  - The athlete biological passport (ABP) was recently implemented in anti-doping
      work and is based on the individual and longitudinal monitoring of haematological
      or urine markers. These may be influenced by illicit procedures performed by some
      athletes with the intent to improve exercise performance. Hence the ABP is a
      valuable tool in the fight against doping. Actually, the passport has been
      defined as an individual and longitudinal observation of markers. These markers
      need to belong to the biological cascade influenced by the application of
      forbidden hormones or more generally, affected by biological manipulations which
      can improve the performance of the athlete. So far, the haematological and
      steroid profile modules of the ABP have been implemented in major sport
      organisations, and a further module is under development. The individual and
      longitudinal monitoring of some blood and urine markers are of interest, because
      the intraindividual variability is lower than the corresponding interindividual
      variability. Among the key prerequisites for the implementation of the ABP is its
      prospect to resist to the legal and scientific challenges. The ABP should be
      implemented in the most transparent way and with the necessary independence
      between planning, interpretation and result management of the passport. To ensure
      this, the Athlete Passport Management Unit (APMU) was developed and the WADA
      implemented different technical documents associated to the passport. This was
      carried out to ensure the correct implementation of a profile which can also
      stand the challenge of any scientific or legal criticism. This goal can be
      reached only by following strictly important steps in the chain of production of
      the results and in the management of the interpretation of the passport. Various
      technical documents have been then associated to the guidelines which correspond
      to the requirements for passport operation. The ABP has been completed very
      recently by the steroid profile module. As for the haematological module,
      individual and longitudinal monitoring have been applied and the interpretation
      cascade is also managed by a specific APMU in a similar way as applied in the
      haematological module. Thus, after exclusion of any possible pathology, specific
      variation from the individual norms will be then considered as a potential misuse
      of hormones or other modulators to enhance performance. 

PMID- 24659507
TI  - Exercise is medicine, for the body and the brain.

PMID- 24659508
TI  - The Athlete Biological Passport: an integral element of innovative strategies in
      antidoping.
AB  - Concern for the health of athletes and integrity of sport resulted in the banning
      of specific substances although many years passed before analytical testing took
      place. Soon doping control programmes became synonymous with urine tests and
      adverse analytical findings. This system has its limits due to the detection
      window of prohibited substances, the timing of sample collections and the
      sophistication of some doping regimens. There have been a number of situations
      where these limits were demonstrated by athletes who proclaimed innocence based
      on passing their analytical tests only to later confess to doping. New strategies
      were called for to protect clean athletes. In the current World Anti-Doping Code,
      there are eight means to an Anti-Doping Rule Violation (ADRV). Article 2.2 states
      that the use of a prohibited substance may be established by any reliable means
      including witness statements, documentary evidence or evaluations of longitudinal
      profiling. In 2006, the World Anti-Doping Agency (WADA) with the support of some
      International Federations (IFs) gathered a group of experts to develop a
      harmonised programme on longitudinal profiling, or serial analysis of indirect
      biomarkers of doping, that was both scientifically and legally robust. This
      culminated in the WADA Athlete Biological Passport (ABP) Operating Guidelines and
      Technical Documents, published in 2009. The ABP is a paradigm that infers the use
      of prohibited substance (or method) by the monitoring of discriminant biomarkers
      over time. The haematological module detects blood manipulation by the use of
      erythropoietic stimulating agents or via blood transfusions. The steroidal module
      aims to identify endogenous anabolic androgenic steroids when administered
      exogenously and other indirect steroid doping substances or methods. Other ABP
      modules (endocrine, 'omics') are being developed. The term passport, first coined
      in 2000, is now defined in the ABP Guidelines as the longitudinal profile and all
      other relevant information including training, competitions and information
      derived from investigations. In the 2015 World Anti-Doping Code, investigations
      or enquiries gathered from other sources will play an even more prominent role. 

PMID- 24659509
TI  - The foot core system: a new paradigm for understanding intrinsic foot muscle
      function.
AB  - The foot is a complex structure with many articulations and multiple degrees of
      freedom that play an important role in static posture and dynamic activities. The
      evolutionary development of the arch of the foot was coincident with the greater
      demands placed on the foot as humans began to run. The movement and stability of
      the arch is controlled by intrinsic and extrinsic muscles. However, the intrinsic
      muscles are largely ignored by clinicians and researchers. As such, these muscles
      are seldom addressed in rehabilitation programmes. Interventions for foot-related
      problems are more often directed at externally supporting the foot rather than
      training these muscles to function as they are designed. In this paper, we
      propose a novel paradigm for understanding the function of the foot. We begin
      with an overview of the evolution of the human foot with a focus on the
      development of the arch. This is followed by a description of the foot intrinsic
      muscles and their relationship to the extrinsic muscles. We draw the parallels
      between the small muscles of the trunk region that make up the lumbopelvic core
      and the intrinsic foot muscles, introducing the concept of the foot core. We then
      integrate the concept of the foot core into the assessment and treatment of the
      foot. Finally, we call for an increased awareness of the importance of the foot
      core stability to normal foot and lower extremity function. 

PMID- 24659510
TI  - Standardised criteria improve accuracy of ECG interpretation in competitive
      athletes: a randomised controlled trial.
AB  - BACKGROUND: Screening to prevent sudden cardiac death remains a contentious topic
      in sport and exercise medicine. The aim of this study was to assess whether the
      use of a standardised criteria tool improves the accuracy of ECG interpretation
      by physicians screening athletes. METHODS: Design: Randomised control trial.
      Study Population: General practitioners with an interest in sports medicine,
      sports physicians, sports medicine registrars and cardiologists from Australia
      and New Zealand were eligible to participate. Outcome Measures: Accuracy,
      sensitivity, specificity and false-positive rates of screening ECG interpretation
      of athletes. Intervention: A two-page standardised ECG criteria tool was provided
      to intervention participants. Control participants undertook 'usual'
      interpretation. RESULTS: 62 physicians, with a mean duration of practice of 16
      years, were randomised to intervention and control. 10 baseline and 30
      postrandomisation athlete ECGs were interpreted by the participants. Intervention
      participants were more likely to be correct: OR 1.72 (95% CI 1.31 to 2.27,
      p<0.001). Correct ECG interpretation was higher in the intervention group, 88.4%
      (95% CI 85.7% to 91.2%), than in the control group, 82.2% (95% CI 78.8% to 85.5%;
      p=0.005). Sensitivity was 95% in the intervention group and 92% in the control
      group (p=0.4), with specificity of 86% and 78%, respectively (p=0.006). There
      were 36% fewer false positives in the intervention group (p=0.006). CONCLUSIONS:
      ECG interpretation in athletes can be improved by using a standardised ECG
      criteria tool. Use of the tool results in lower false-positive rates; this may
      have implications for screening recommendations. TRIAL REGISTRATION NUMBER:
      ACTRN12612000641897.

PMID- 24659512
TI  - The management of food cravings and thirst in hemodialysis patients: A
      qualitative study.
AB  - This study set out to explore the experience of food cravings and thirst, and
      their management strategies in patients on hemodialysis. Semi-structured
      interviews with N = 32 hemodialysis patients were analyzed thematically. Findings
      indicated that food cravings and thirst were common in everyday life of patients
      and resulted in different emotional responses. A combination of cognitive and
      behavioral strategies was employed, including avoidance, controlled consumption,
      and substitution. Self-monitoring and compensatory strategies were also used to
      prevent or compensate for lapses. These findings lay the groundwork for future
      work aimed to improve adherence in end-stage renal disease patients. 

PMID- 24659511
TI  - In vivo blood flow imaging of inflammatory human skin induced by tape stripping
      using optical microangiography.
AB  - Vasculature response is a hallmark for most inflammatory skin disorders. Tape
      stripping on human skin causes a minor inflammation which leads to changes in
      microvasculature. In this study, optical microangiography (OMAG), noninvasive
      volumetric microvasculature in vivo imaging method, has been used to track the
      vascular responses after tape stripping. Vessel density has been quantified and
      used to correlate with the degree of skin irritation. The proved capability of
      OMAG technique in visualizing the microvasculature network under inflamed skin
      condition can play an important role in clinical trials of treatment and
      diagnosis of inflammatory skin disorders.

PMID- 24659513
TI  - Management of low back pain in Ghana: a survey of self-reported practice.
AB  - BACKGROUND AND PURPOSE: Practice variation exists in the physiotherapy management
      of low back pain (LBP) across several countries. Previous studies indicate that
      treatment strategies used may not always be in line with evidence-based practice.
      Most of these studies however were conducted in developed countries. This study
      sought to investigate the management of LBP in Ghana in order to add to the
      emergent literature regarding practice in developing nations. METHODS: A web
      based self-report questionnaire was made available to all eligible members of the
      Ghana Physiotherapy Association. RESULTS: The survey achieved a response rate of
      67%. Over 60% of physiotherapists in Ghana had less than 5 years of practice
      experience, worked in large facility hospitals and had no post-graduate further
      training. Most LBP patients seen were chronic, and over 60% of treatment sessions
      used multiple therapies and included exercises, advice, massage, electrotherapy
      and manual therapy. CONCLUSION: This first mapping of physiotherapy management of
      LBP in Ghana shows an overt multimodal approach. There was potential good
      practice with the high use of exercise and advice, the equally high utilization
      of passive treatments however showed variance to recommendations of guidelines.
      The findings of this study have implications for clinical practice and
      physiotherapy education and research.

PMID- 24659514
TI  - Immunoassay-based serum hepcidin reference range measurements in healthy
      children: differences among age groups.
AB  - BACKGROUND: Hepcidin is a peptide hormone that plays a key role in regulating
      iron absorption from the small intestine and body iron distribution. Alterations
      in hepcidin concentrations have been associated with chronic inflammatory
      conditions or inherited diseases of iron metabolism. The aim of our study was to
      evaluate healthy children in order to define normal reference range of serum
      hepcidin concentrations. The universal use of a reliable commercial ELISA kit
      gives the ability to compare our results with those from previous studies.
      METHODS: We evaluated 180 healthy children (88 boys, mean age: 67.55 +/- 39.26
      months, median: 60, range: 24-156 months) aged 2-12 years, using an immunoassay
      kit. RESULTS: Hepcidin median values were 46.94 ng/ml for boys and 46.79 ng/ml
      for girls. No significant differences were observed between boys and girls. There
      seem to be significantly higher values of hepcidin in older children (10-12 years
      old). This trend was constant and statistically significant in boys after gender
      and age group stratification. Although this trend was more prominent in girls, it
      was not statistically significant. CONCLUSIONS: This study aims at setting up
      reference values for serum hepcidin concentrations in healthy pediatric
      population by using a well-established laboratory kit. The difference in hepcidin
      concentrations in older children could be attributed to different growth rates.
      Additionally, differences between values in adults and children could reflect
      alterations in iron metabolism between those two age groups.

PMID- 24659515
TI  - Consensus design of a NOD receptor leucine rich repeat domain with binding
      affinity for a muramyl dipeptide, a bacterial cell wall fragment.
AB  - Repeat proteins have recently emerged as especially well-suited alternative
      binding scaffolds due to their modular architecture and biophysical properties.
      Here we present the design of a scaffold based on the consensus sequence of the
      leucine rich repeat (LRR) domain of the NOD family of cytoplasmic innate immune
      system receptors. Consensus sequence design has emerged as a protein design tool
      to create de novo proteins that capture sequence-structure relationships and
      interactions present in nature. The multiple sequence alignment of 311 individual
      LRRs, which are the putative ligand-recognition domain in NOD proteins, resulted
      in a consensus sequence protein containing two internal and N- and C-capping
      repeats named CLRR2. CLRR2 protein is a stable, monomeric, and cysteine free
      scaffold that without any affinity maturation displays micromolar binding to
      muramyl dipeptide, a bacterial cell wall fragment. To our knowledge, this is the
      first report of direct interaction of a NOD LRR with a physiologically relevant
      ligand. 

PMID- 24659516
TI  - Population survey of phytoseiid mites and spider mites on peach leaves and wild
      plants in Japanese peach orchard.
AB  - A population survey of phytoseiid mites and spider mites was conducted on peach
      leaves and wild plants in Japanese peach orchards having different pesticide
      practices. The phytoseiid mite species composition on peach leaves and wild
      plants, as estimated using quantitative sequencing, changed during the survey
      period. Moreover, it varied among study sites. The phytoseiid mite species
      compositions were similar between peach leaves and some wild plants, such as
      Veronica persica, Paederia foetida, Persicaria longiseta, and Oxalis corniculata
      with larger quantities of phytoseiid mites, especially after mid-summer. A PCR
      based method to detect the ribosomal ITS sequences of Tetranychus kanzawai and
      Panonychus mori from phytoseiid mites was developed. Results showed that Euseius
      sojaensis (specialized pollen feeder/generalist predator) uses both spider mites
      as prey in the field.

PMID- 24659517
TI  - Determination of discriminating dose and evaluation of amitraz resistance status
      in different field isolates of Rhipicephalus (Boophilus) microplus in India.
AB  - Field tick isolates of Rhipicephalus (Boophilus) microplus were collected from
      eleven districts located in the northern and eastern states of India to access
      the resistance status to "Amitraz". Adult immersion test was optimized using
      laboratory reared acaricide susceptible IVRI-I line and minimum effective
      concentration was determined as 487.7 ppm with 95 % confidence interval of 455.8
      521.8. The discriminating concentration was determined as 975.4 ppm and was
      tested on female ticks collected by two stage stratified sampling from organized
      dairy farms and villages. Based on three variables, viz.,mortality, egg masses
      and reproductive index, the resistance level was categorized.Resistance to
      amitraz was detected at level I in 3 isolates (RF = 1.56-5.0), at level II in 6
      isolates (RF = 9.3-23.3) and at level III in 1 isolate (RF = 27.3) whereas one
      isolate was found susceptible. The highest resistance was found in the SKR
      isolate (RF = 27.3) and minimal resistance was detected in the N-24P isolate (RF
      = 1.56). These experimental data will help in designing tick control strategy
      which is suffering from acaricide failure and to overcome development of
      resistance in ticks.

PMID- 24659518
TI  - Detachment of hard ticks (Acari: Ixodidae) from hunted sika deer (Cervus nippon).
AB  - Ixodid ticks were collected from 13 sika deer, Cervus n.nippon, shot in the Boso
      Peninsula in central Japan from late February to early March 1999. Haemaphysalis
      megaspinosa was the most abundant species of the adults collected, although
      Haemaphysalis longicornis, H. flava, H. kitaokai, H. cornigera, Ixodes ovatus,
      and Amblyomma testudinarium were also collected. Males were more abundant than
      females for H. longicornis, H. megaspinosa, H. flava, and H. kitaokai. Ticks that
      had inserted their hypostome into its host skin (designated attached) were
      distinguished from those that were detached and on the host's surface. A greater
      fraction of males than females of all four species were detached. Females were
      classified in three feeding stages (engorged, partially engorged, and unfed).
      More H. longicornis and H. megaspinosa unfed female ticks than engorged and
      partially-engorged female ticks were collected detached. Our results indicated
      that H. megaspinosa, H. longicornis, H. flava, and H. kitaokai male ticks
      detached sooner than female ticks after their host died.

PMID- 24659519
TI  - Efficacy of chemical repellents against Otobius megnini (Acari: Argasidae) and
      three species of ixodid ticks.
AB  - Otobius megnini (Duges), often referred to as the ear tick or spinose ear tick,
      is a one-host tick native to the southwestern United States and Mexico.
      Infestations of this species can cause severe irritation and may affect breeding
      behavior in the host. Although chemical repellents are commonly used as an
      alternative approach to conventional arthropod vector control, information on
      repellency against O. megnini is lacking. This study compared repellency of
      ammonia, BioUD((r)), 98.25% DEET, garlic pepper tea, permanone, and pyrethrin
      with piperonyl butoxide, against larvae stages of O. megnini, Amblyomma
      americanum (L.), Dermacentor variabilis (Say), and Rhipicephalus sanguineus
      (Latreille). To test for repellency, tick movement was recorded at 30 s intervals
      for five min after introduction to a partially treated piece of filter paper.
      Results showed larvae of O. megnini exhibited less aversion to the chemicals
      tested when compared to the other tick species.

PMID- 24659520
TI  - Do aphids actively search for ant partners?
AB  - The aphid-ant mutualistic relationships are not necessarily obligate for neither
      partners but evidence is that such interactions provide them strong advantages in
      terms of global fitness. While it is largely assumed that ants actively search
      for their mutualistic partners namely using volatile cues; whether winged aphids
      (i.e., aphids' most mobile form) are able to select ant-frequented areas had not
      been investigated so far. Ant-frequented sites would indeed offer several
      advantages for these aphids including a lower predation pressure through ant
      presence and enhanced chances of establishing mutuaslistic interactions with
      neighbor ant colonies. In the field, aphid colonies are often observed in higher
      densities around ant nests, which is probably linked to a better survival ensured
      by ants' services. Nevertheless, this could also result from a preferential
      establishment of winged aphids in ant-frequented areas. We tested this last
      hypothesis through different ethological assays and show that the facultative
      myrmecophilous black bean aphid, Aphis fabae L., does not orientate its search
      for a host plant preferentially toward ant-frequented plants. However, our
      results suggest that ants reduce the number of winged aphids leaving the newly
      colonized plant. Thus, ants involved in facultative myrmecophilous interactions
      with aphids appear to contribute to structure aphid populations in the field by
      ensuring a better establishment and survival of newly established colonies rather
      than by inducing a deliberate plant selection by aphid partners based on the
      proximity of ant colonies. 

PMID- 24659521
TI  - Impact of UCP2 polymorphism on long-term exercise-mediated changes in
      adipocytokines and markers of metabolic syndrome.
AB  - BACKGROUND AND AIMS: Variations in genes involved in energy expenditure affect
      aerobic exercise efficiency, but it remains unclear whether the effect of aerobic
      exercise on adipocytokines is modified by the obesity-associated genotypes in the
      uncoupling protein 2 gene (UCP2). The purpose of this study was to assess whether
      genetic variation in UCP2 may affect exercise-mediated changes in adipocytokines
      and markers of metabolic syndrome in postmenopausal obese women. METHODS: Forty
      two sedentary postmenopausal obese women (age 52.74 +/- 6.39 years) participated
      in this study. Participants were encouraged to train for 3 days a week, for 6
      months, for 60 min per session of treadmill walking/running at 60 % [Formula: see
      text]. Subjects were genotyped for the 45-bp insertion/deletion (I/D)
      polymorphism in the 3'-untranslated region (UTR) of UCP2. RESULTS: Among the
      subjects, 23 (57.1 %) and 19 (42.9 %), were deletion homozygotes (DD) and ID
      heterozygotes, respectively. For DD homozygotes, body weight, body mass index
      (BMI), % body fat, and waist circumference, and body weight, BMI, and waist
      circumference of ID heterozygotes, were significantly decreased after the
      exercise program. There were no significant changes in metabolic markers in
      individuals with the ID genotype, whereas insulin and HOMA-IR in individuals with
      the DD genotype were significantly decreased after the exercise program. In DD
      homozygotes, but not in ID heterozygotes, adiponectin was significantly
      increased, and leptin, TNF-alpha, and IL-6 were significantly decreased after
      exercise training. CONCLUSIONS: Exercise-mediated changes in insulin resistance
      and adiponectin levels may be affected by genotypes in the 3'UTR I/D polymorphism
      in UCP2 in postmenopausal obese women.

PMID- 24659522
TI  - Magnetic resonance imaging phenotyping of Becker muscular dystrophy.
AB  - INTRODUCTION: There is little information on magnetic resonance imaging (MRI)
      phenotypes of Becker muscular dystrophy (BMD). This study presents the MRI
      phenotyping of the upper and lower extremities of a large cohort of BMD patients.
      METHODS: In this retrospective study, MRI images of 33 BMD subjects were
      evaluated for severity, distribution, and symmetry of involvement. RESULTS: Teres
      major, triceps long head, biceps brachii long head, gluteus maximus, gluteus
      medius, vasti, adductor longus, adductor magnus, semitendinosus, semimembranosus,
      and biceps femoris muscles showed the highest severity and frequency of
      involvement. All analyzed muscles had a high frequency of symmetric involvement.
      There was significant variability of involvement between muscles within some
      muscle groups, most notably the arm abductors, posterior arm muscles, medial
      thigh muscles, and lateral hip rotators. CONCLUSIONS: This study showed a
      distinctive pattern of involvement of extremity muscles in BMD subjects.

PMID- 24659523
TI  - Effects of calcium phosphate composition in sputter coatings on in vitro and in
      vivo performance.
AB  - Calcium phosphate (CaP) ceramic coatings have been used to enhance the
      biocompatibility and osteoconductive properties of metallic implants. The
      chemical composition of these ceramic coatings is an important parameter, which
      can influence the final bone performance of the implant. In this study, the
      effect of phase composition of CaP-sputtered coatings was investigated on in
      vitro dissolution behavior and in vivo bone response. Coatings were prepared by a
      radio frequency (RF) magnetron sputtering technique; three types of CaP target
      materials were used to obtain coatings with different stoichiometry and calcium
      to phosphate ratios (hydroxyapatite (HA), alpha-tricalciumphosphate (alpha-TCP),
      and tetracalciumphosphate (TTCP)) were compared with non-coated titanium
      controls. The applied ceramic coatings were characterized by X-ray diffraction,
      Fourier transform infrared spectroscopy, scanning electron microscopy, and
      inductively coupled plasma optical emission spectroscopy. The in vitro
      dissolution/precipitation of the CaP coatings was evaluated using immersion tests
      in simulated body fluid (SBF). To mimic the in vivo situation, identical CaP
      coatings were also evaluated in a femoral condyle rabbit model. TCPH and TTCPH
      showed morphological changes during 4-week immersion in SBF. The results of bone
      implant contact (BIC) and peri-implant bone volume (BV) showed a similar response
      for all experimental coatings. An apparent increase in tartrate resistant acid
      phosphatase (TRAP) positive staining was observed in the peri-implant region with
      decreasing coating stability. In conclusion, the experimental groups showed
      different coating properties when tested in vitro and an apparent increase in
      bone remodeling with increasing coating dissolution in vivo.

PMID- 24659524
TI  - Involvement of herb-herb interactions in the influences of Radix Scutellaria and
      Coptis Chinensis on the bioavailability of the anthraquinones form Rhei Rhizoma
      in rats.
AB  - Xiexin decoction (XXD) is composed of Rhei Rhizoma (DH), Radix Scutellaria (HQ),
      and Coptis Chinensis (HL). Free anthraquinones in DH are the basic effective
      constituents in XXD. Reportedly, HL decreases the bioavailability of the
      anthraquinones, while HQ antagonizes the effect of HL. In this study, we aimed to
      determine the underlying mechanisms. The metabolisms of anthraquinones by
      intestinal flora were studied using rat fecal suspension (RFS); the metabolisms
      of rhein (a typical anthraquinone in DH) by rat intestine and liver were studied
      using rat intestine microsomes (RIMs) and rat liver microsomes (RLMs),
      respectively; the intestinal transport of rhein was studied using everted gut
      sacs. The results showed that HL decreased the amount of the free anthraquinones
      after incubation in RFS and inhibited the intestinal transport of rhein, but HQ
      antagonized the effect of HL. On the other hand, HQ strongly inhibited the
      glucuronidation of rhein in both RIMs and RLMs. The results suggested that HL
      decreased the oral bioavailability of the anthraquinones due to inhibiting the
      conversion of conjugated anthraquinones to free anthraquinones by intestinal
      flora and decreasing the intestinal transport of the anthraquinones; HQ
      confronted the effect of HL by inhibiting the glucuronidation of the
      anthraquinones in intestine and weakening the inhibitory effects of HL.

PMID- 24659525
TI  - Reductive metabolism of nabumetone by human liver microsomal and cytosolic
      fractions: exploratory prediction using inhibitors and substrates as marker
      probes.
AB  - The metabolic reduction of nabumetone was examined by inhibition and correlation
      studies using human liver microsomes and cytosol. This reduction was observed in
      both fractions, with the V(max) values for reduction activity being approximately
      fourfold higher, and the V(max)/K(m) values approximately three-fold higher, in
      the microsomes than in the cytosol. The reduction of nabumetone was inhibited by
      18beta-glycyrrhetinic acid, an 11beta-hydroxysteroid dehydrogenase (11beta-HSD)
      inhibitor, in the microsomal fraction. The reduction activity was also inhibited
      by quercetin and menadione [carbonyl reductase (CBR) inhibitors], and by
      phenolphthalein and medroxyprogesterone acetate [potent inhibitors of aldo-keto
      reductase (AKR) 1C1, 1C2 and 1C4] in the cytosol. A good correlation (r2 = 0.93)
      was observed between the reduction of nabumetone and of cortisone, as a marker of
      11beta-HSD activity, in the microsomal fractions. There was also an excellent
      relationship between reduction of nabumetone and of the AKR1C substrates,
      acetohexamide, and ethacrynic acid (r 2 = 0.92 and 0.93, respectively), in the
      cytosol fractions. However, a poor correlation was observed between the formation
      of 4-(6-methoxy-2-naphthyl)-butan-2-ol (MNBO) from nabumetone and CBR activity
      (with 4-benzoyl pyridine reduction as a CBR substrate) in the cytosol fractions
      (r2 = 0.24). These findings indicate that nabumetone may be metabolized by 11beta
      HSD in human liver microsomes, and primarily by AKR1C4 in human liver cytosol,
      although multiple enzymes in the AKR1C subfamily may be involved. It cannot be
      completely denied that CBR is involved to some extent in the formation of MNBO
      from nabumetone in the cytosol fraction.

PMID- 24659526
TI  - To the editor.

PMID- 24659527
TI  - Validation of the only commercially available immunoassay for synthetic
      cathinones in urine: Randox Drugs of Abuse V Biochip Array Technology.
AB  - Deterrence of synthetic cathinone abuse is hampered by the lack of a high
      throughput immunoassay screen. The Randox Drugs of Abuse V (DOA-V) Biochip Array
      Technology contains two synthetic cathinone antibodies: Bath Salt I (BSI) targets
      mephedrone/methcathinone and Bath Salt II (BSII) targets 3',4'
      methylenedioxypyrovalerone (MDPV)/3',4'-methylenedioxy-alpha
      pyrrolidinobutiophenone (MDPBP). We evaluated DOA-V synthetic cathinones
      performance and conducted a full validation on the original assay with
      calibrators reconstituted in water, and the new assay with calibrators prepared
      in lyophilized urine; both utilized the same antibodies and were run on the fully
      automated Evidence(r) Analyzer. We screened 20 017 authentic military urine
      specimens and confirmed positives by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) for 28 synthetic cathinones. Limits of detection (LOD)
      for the original and new assays were 0.35 and 0.18 (BSI), and 8.5 and 9.2 ug/L
      (BSII), respectively. Linearity was acceptable (R(2)  >0.98); however, a large
      negative bias was observed with in-house prepared calibrators. Intra-assay
      imprecision was <20% BSI-II, while inter-assay imprecision was 18-42% BSI and
      <22% BSII. Precision was acceptable for Randox controls. Cross-reactivities of
      many additional synthetic cathinones were determined. Authentic drug-free
      negative urine pH <4 produced false positive results for BSI (6.3 ug/L) and BSII
      (473 ug/L). Oxidizing agents reduced BSI and increased BSII results. Sensitivity,
      specificity, and efficiency of 100%, 52.1%, and 53.0% were obtained at
      manufacturer's proposed cut-offs (BSI 5 ug/L, BSII 30 ug/L). Performance improved
      if cut-off concentrations increased (BSI 7.5 ug/L, BSII 40 ug/L); however, there
      were limited confirmed positive specimens. Currently, this is the first and only
      fully validated immunoassay for preliminary detection of synthetic cathinones in
      urine. Published 2014. This article is a U.S. Government work and is in the
      public domain in the USA.

PMID- 24659528
TI  - Evaluating the evidence for the relationship between passive smoking and lung
      cancer.

PMID- 24659529
TI  - Heterologous expression and characterization of human cellular glutathione
      peroxidase mutants.
AB  - Cellular glutathione peroxidase (GPx1; EC1.11.1.9) is a major intracellular
      antioxidant selenoenzyme in mammals. However, the complicated expression
      mechanism of selenocysteine (Sec)-containing protein increases the difficulty of
      expressing human GPx1 (hGPx1) in Escherichia coli (E. coli). In this study, hGPx1
      gene was cloned from a cDNA library of the human hepatoma cell line HepG2. The
      codon UGA encoding Sec49 of hGPx1 was first mutated to UGC encoding cysteine
      (Cys) and then biosynthetically converted to Sec during expression in an E. coli
      BL21(DE3)cys auxotrophic system. Seleno-GPx1Sec displayed a low GPx activity of
      522 U/MUmol. To improve the activity, the other five Cys residues (C2, C78, C115,
      C156, C202) were mutated to serine (Ser) in one hGPx1 molecule. The mutant seleno
      hGPx1Ser showed a high activity of 5278 U/MUmol, which was more than 10-fold
      enhanced as compared with seleno-GPx1Sec . The activity was the highest among all
      of those seleno-proteins obtained by this method so far. Kinetic analysis of
      seleno-hGPx1Ser showed a typical ping-pong mechanism, which was similar to those
      of natural GPxs. This research will be of value in overcoming the problem of
      limited sources of natural GPx and substantially promotes the research of the
      characterization of GPx. (c) 2014 IUBMB Life, 66(3):212-219, 2014.

PMID- 24659530
TI  - Serum copeptin and midregion proadrenomedullin (MR-proADM) after an
      ultramarathon.
AB  - BACKGROUND: Although it is widely acknowledged that physical activity confers
      several health benefits, it remains uncertain whether strenuous and physically
      demanding exercise might determine biological effects that might turn to be
      ultimately unfavorable for health. Copeptin and midregion proadrenomedullin (MR
      proADM) are emerging cardiovascular and stress biomarkers, but little is known
      about the influence of strenuous physical exercise on their concentrations.
      METHODS: The present study was performed to investigate the variation of copeptin
      and MRproADM, along with that of serum creatinine and estimated glomerular
      filtration rate before and after a 60 km ultramarathon in 16 healthy Caucasian
      males. RESULTS: The serum concentrations of both copeptin and MR-proADM
      remarkably increased after the 60 km run, by 6.4 times (interquartile range
      (IQR), 2.710.4) and 2.3 times (IQR, 1.8-2.6), respectively. A highly significant
      correlation was observed between the increase of creatinine and MR-proADM, but
      not between serum creatinine and copeptin. The percentage of subjects exhibiting
      values above the upper limit of the reference range in male was 0% for both
      copeptin and MR-proADM before the ultramarathon, but increased to respectively 81
      and 63% postexercise. CONCLUSION: The evidence that an ultramarathon causes a
      substantial increase of copeptin and MR-proADM raises doubts as to whether
      exhaustive exercise might be considered globally beneficial or even safe,
      especially in unfit or/and untrained population.

PMID- 24659531
TI  - 13C-MFA delineates the photomixotrophic metabolism of Synechocystis sp. PCC 6803
      under light- and carbon-sufficient conditions.
AB  - The central carbon metabolism of cyanobacteria is under debate. For over 50
      years, the lack of alpha-ketoglutarate dehydrogenase has led to the belief that
      cyanobacteria have an incomplete TCA cycle. Recent in vitro enzymatic experiments
      suggest that this cycle may in fact be closed. The current study employed (13) C
      isotopomers to delineate pathways in the cyanobacterium Synechocystis sp. PCC
      6803. By tracing the incorporation of supplemented glutamate into the downstream
      metabolites in the TCA cycle, we observed a direct in vivo transformation of
      alpha-ketoglutarate to succinate. Additionally, isotopic tracing of glyoxylate
      did not show a functional glyoxylate shunt and glyoxylate was used for glycine
      synthesis. The photomixotrophic carbon metabolism was then profiled with (13) C
      MFA under light and carbon-sufficient conditions. We observed that: (i) the in
      vivo flux through the TCA cycle reactions (alpha-ketoglutarate -> succinate) was
      minimal (<2%); (ii) the flux ratio of CO2 fixation was six times higher than that
      of glucose utilization; (iii) the relative flux through the oxidative pentose
      phosphate pathway was low (<2%); (iv) high flux through malic enzyme served as a
      main route for pyruvate synthesis. Our results improve the understanding of the
      versatile metabolism in cyanobacteria and shed light on their application for
      photo-biorefineries. 

PMID- 24659533
TI  - Quantitative muscle ultrasound versus quantitative magnetic resonance imaging in
      facioscapulohumeral dystrophy.
AB  - INTRODUCTION: Ultrasound and magnetic resonance imaging (MRI) are non-invasive
      methods that can be performed repeatedly and without discomfort. In the
      assessment of neuromuscular disorders it is unknown if they provide complementary
      information. In this study we tested this for patients with facioscapulohumeral
      muscular dystrophy (FSHD). METHODS: We performed quantitative muscle ultrasound
      (QMUS) and quantitative MRI (QMRI) of the legs in 5 men with FSHD. RESULTS: The
      correlation between QMUS-determined z-scores and QMRI-determined muscle fraction
      and T1 signal intensity (SI) was very high. QMUS had a wider dynamic range than
      QMRI, whereas QMRI could detect inhomogeneous distribution of pathology over the
      length of the muscles. CONCLUSIONS: Both QMUS and QMRI are well suited for
      imaging muscular dystrophy. The wider dynamic range of QMUS can be advantageous
      in the follow-up of advanced disease stages, whereas QMRI seems preferable in
      pathologies such as FSHD that affect deep muscle layers and show inhomogeneous
      abnormality distributions.

PMID- 24659532
TI  - Capping motifs stabilize the leucine-rich repeat protein PP32 and rigidify
      adjacent repeats.
AB  - Capping motifs are found to flank most beta-strand-containing repeat proteins. To
      better understand the roles of these capping motifs in organizing structure and
      stability, we carried out folding and solution NMR studies on the leucine-rich
      repeat (LRR) domain of PP32, which is composed of five tandem LRR, capped by
      alpha-helical and beta-hairpin motifs on the N- and C-termini. We were able to
      purify PP32 constructs lacking either cap and containing destabilizing
      substitutions. Removing the C-cap results in complete unfolding of PP32. Removing
      the N-cap has a much less severe effect, decreasing stability but retaining much
      of its secondary structure. In contrast, the dynamics and tertiary structure of
      the first two repeats are significantly perturbed, based on (1)H-(15)N relaxation
      studies, chemical shift perturbations, and residual dipolar couplings. However,
      more distal repeats (3 to C-cap) retain their native tertiary structure. In this
      regard, the N-cap drives the folding of adjacent repeats from what appears to be
      a molten-globule-like state. This interpretation is supported by extensive
      analysis using core packing substitutions in the full-length and N-cap-truncated
      PP32. This work highlights the importance of caps to the stability and structural
      integrity of beta-strand-containing LRR proteins, and emphasizes the different
      contributions of the N- and C-terminal caps.

PMID- 24659534
TI  - A longitudinal test of impulsivity and depression pathways to early binge eating
      onset.
AB  - OBJECTIVE: The very early engagement in bulimic behaviors, such as binge eating,
      may be influenced by factors that dispose individuals to impulsive action as well
      as by factors that dispose individuals to depressive symptomatology. Using a
      longitudinal design, we conducted the first test of the simultaneous operation of
      both risk factors as children transition from elementary to middle school.
      METHOD: In a sample of 1,906 children, we assessed risk for impulsive action
      (negative urgency, which is the tendency to act rashly when distressed, and
      eating expectancies, which are learned anticipations that eating will alleviate
      negative mood) and risk for depression (negative affect and depressive
      symptomatology) and binge eating behavior at three time points using a
      longitudinal design: the end of fifth grade (last year of elementary school: T0),
      the beginning of sixth grade (first year of middle school: T1), and the end of
      sixth grade (T2). RESULTS: Both the impulsive action and depression pathways
      predicted very early engagement in binge eating: each accounted for variance
      beyond the other. Mediation tests found that T1 eating expectancies mediated the
      predictive influence of T0 negative urgency on T2 binge eating (z = 2.45, p <
      .01) and that T1 depressive symptoms mediated the influence of T0 negative affect
      on T2 binge eating (z = 2.04, p < .05). DISCUSSION: In children, elevated levels
      of both negative urgency and negative affect predict early binge eating. This
      finding has important clinical implications because there are different
      interventions for the two different risk processes.

PMID- 24659535
TI  - Multiscale mathematical modeling and simulation of cellular dynamical process.
AB  - Epidermal homeostasis is maintained by dynamic interactions among molecules and
      cells at different spatiotemporal scales. Mathematical modeling and simulation is
      expected to provide clear understanding and precise description of multiscaleness
      in tissue homeostasis under systems perspective. We introduce a stochastic
      process-based description of multiscale dynamics. Agent-based modeling as a
      framework of multiscale modeling to achieve consistent integration of definitive
      subsystems is proposed. A newly developed algorithm that particularly aims to
      perform stochastic simulations of cellular dynamical process is introduced.
      Finally we review applications of multiscale modeling and quantitative study to
      important aspects of epidermal and epithelial homeostasis.

PMID- 24659536
TI  - Fluorescent protein-based reporters of the actin cytoskeleton in living plant
      cells: fluorophore variant, actin binding domain, and promoter considerations.
AB  - Genetically encoded filamentous actin (F-actin) reporters designed based on
      fluorescent protein fusions to F-actin binding domains of actin regulatory
      proteins have emerged as powerful tools to decipher the role of the actin
      cytoskeleton in plant growth and development. However, these probes could
      interfere with the function of endogenous actin binding proteins and in turn
      impact actin organization and plant growth. We therefore surveyed F-actin
      labeling and compared organ growth in Arabidopsis thaliana lines expressing a
      variety of F-actin markers. Here we show that the variant of fluorescent protein,
      type of actin binding domain, and the promoter that drives reporter expression
      can influence the quality of F-actin labeling particularly in stable plant lines.
      For example, older red fluorescent protein (RFP)-based probes such as DsRed2 and
      mOrange induced more aberrant labeling compared to the newer RFP-based, mCherry,
      GFP, and GFP-derived fluorophores such as YFP and CFP. Moreover, qualitative and
      quantitative analyses revealed differences in F-actin organization in seedlings
      expressing Talin- and Lifeact-based reporters in some cell types compared to the
      fimbrin actin binding domain 2 (ABD2)-based reporters. Finally, the use of the
      ubiquitin10 (UBQ10) promoter to drive expression of the GFP-ABD2-GFP probe
      minimized loss of fluorescence and growth defects observed in the 35S-driven
      version. Taken together, this study shows that care must be taken in the
      interpretation of data derived from stable expression of certain F-actin
      reporters and that using alternative promoters such as UBQ10 can overcome some of
      the pitfalls that accompany the use of in vivo F-actin probes in plants. (c) 2014
      Wiley Periodicals, Inc. 

PMID- 24659537
TI  - NAC transcription factor gene regulatory and protein-protein interaction networks
      in plant stress responses and senescence.
AB  - Plant-specific NAM/ATAF/CUC (NAC) transcription factors (TFs) have recently
      received considerable attention due to their significant roles in plant
      development and stress signaling. Here, we summarize progress in understanding
      NAC TFs in stress responses and senescence. We focus on interactions between the
      DNA-binding NAC domain and target genes, and between the large, mostly disordered
      transcription regulatory domain of NAC TFs and protein interaction partners.
      Recent studies have identified both up-stream regulators of NAC genes and down
      stream NAC target genes, outlining regulatory networks associated with NAC
      protein interactions. This connects molecular interactions and signal pathway
      intersections with biological functions with promising use in agriculture. (c)
      2014 IUBMB Life, 66(3):156-166, 2014.

PMID- 24659538
TI  - Feasibility of polyelectrolyte-driven Fab fragment separation.
AB  - The use of antigen-binding fragments (Fabs) as biotherapeutic agents is gaining
      interest and thus requires development of adequate purification strategies aimed
      at separating Fabs from other proteins. Thus, the feasibility of using a
      copolymer for separation of Fabs from monoclonal antibodies (mAbs) and fragment
      constant regions (Fcs) was evaluated, employing a blend of purified solutions of
      these proteins. The use of a copolymer exerting both hydrophobic as well as
      anionic properties resulted in high precipitation yields for both the mAb and Fc
      fragment, even at ionic strength of 150 mM NaCl. On the contrary, Fabs exhibited
      reduced precipitation yields upon copolymer addition. These observations are
      attributed to differences in protein physicochemical parameters, allowing mAbs
      and Fcs to be precipitated via conjoint electrostatic and hydrophobic
      interactions. In contrast, Fabs were mainly precipitated via electrostatic
      interactions, being reduced at higher ionic strength. This finding was
      corroborated by hydrophobicity analysis using 2-p-toluidinonaphthalene-6
      sulfonate, showing enhanced hydrophobicity of Fcs compared to mAbs alone, while
      Fabs exhibited the lowest hydrophobicity. Within the context of increasing demand
      for Fabs as therapeutic proteins, these results may open up a simpler
      purification strategy for this protein class, potentially also to be implemented
      within the context of polymer-driven protein purification during fermentation. 

PMID- 24659539
TI  - LPS and IL-1 differentially activate mouse and human astrocytes: role of CD14.
AB  - Treatment of cultures with toll-like receptor (TLR) ligands or cytokines has
      become a popular approach to investigate astrocyte neuroinflammatory responses
      and to simulate the neural environment in various CNS disorders. However, despite
      much effort, the mechanism of astrocyte activation such as their responses to the
      TLR ligands and IL-1 remain highly debated. We compared highly pure primary mouse
      and human astrocyte cultures in their ability to produce proinflammatory
      mediators (termed "A1") and immunoregulatory mediators (termed "A2") in response
      to LPS, poly IC, and IL-1 stimulation. In human astrocytes, IL-1 induced both A1
      and A2 responses, poly IC induced mostly A2, and LPS induced neither. In mouse
      astrocytes, LPS induced mostly an A1-predominant response, poly IC induced both
      A1 and A2, and IL-1 neither. In addition, mouse astrocytes produce abundant IL-1
      protein, whereas human astrocytes did not, despite robust IL-1 mRNA expression.
      Of the TLR4 receptor complex proteins, human astrocytes expressed TLR4 and MD2
      but not CD14, whereas mouse astrocytes expressed all three. Mouse astrocyte CD14
      (cell-associated and soluble) was potently upregulated by LPS. Silencing TLR4 or
      CD14 by siRNA suppressed LPS responses in mouse astrocytes. In vivo, astrocytes
      in LPS-injected mouse brains also expressed CD14. Our results show striking
      differences between human and mouse astrocytes in the use of TLR/IL-1R and
      subsequent downstream signaling and immune activation. IL-1 translational block
      in human astrocytes may be a built-in mechanism to prevent autocrine and
      paracrine cell activation and neuroinflammation. These results have important
      implications for translational research of human CNS diseases.

PMID- 24659540
TI  - Topologically ordered magnesium-biopolymer hybrid composite structures.
AB  - Magnesium and its alloys are intriguing as possible biodegradable biomaterials
      due to their unique combination of biodegradability and high specific mechanical
      properties. However, uncontrolled biodegradation of magnesium during implantation
      remains a major challenge in spite of the use of alloying and protective
      coatings. In this study, a hybrid composite structure of magnesium metal and a
      biopolymer was fabricated as an alternative approach to control the corrosion
      rate of magnesium. A multistep process that combines metal foam production and
      injection molding was developed to create a hybrid composite structure that is
      topologically ordered in all three dimensions. Preliminary investigations of the
      mechanical properties and corrosion behavior exhibited by the hybrid Mg-polymer
      composite structures suggest a new potential approach to the development of Mg
      based biomedical devices.

PMID- 24659541
TI  - Examination of the difficulties in emotion regulation scale and its relation to
      disordered eating in a young female sample.
AB  - OBJECTIVE: Difficulties with emotion regulation is considered an important
      maintaining factor of disordered eating. One of the most commonly used measures
      of this construct is the Difficulties in Emotion Regulation Scale (DERS). The aim
      of this study was to explore the factor structure of this measure in young
      females and to examine its reliability and validity with respect to disordered
      eating. METHOD: Females aged 17-25 years (M age = 19.6 years, N = 486) were
      examined in the analyses. Confirmatory factor analyses were conducted followed by
      regression analyses examining the DERS subscales as predictors of eating disorder
      severity and disordered eating behaviors. RESULTS: The original 6-factor 36-item
      model did not fit well and analyses indicated a 6-factor 30-item solution was a
      more suitable fit for our population. Validity and reliability of the 30-item
      solution were found to be acceptable. Regression analyses also indicated the 36-
      and 30-item models were able to adequately predict eating disorder severity and
      disordered eating behaviors with the "Awareness" and "Goals" subscales being
      predictors of the former, and the "Impulsivity" subscale being a significant
      predictor of the latter. DISCUSSION: The overall findings suggest that an
      abbreviated version of the DERS might be more appropriate than the original
      version with young females and that this measure exhibits stronger relationships
      with eating disorder severity and disordered eating behaviors than the longer
      version. Further examinations of the psychometric properties of the DERS with
      clinical populations are indicated.

PMID- 24659542
TI  - Oxidation contributes to low glutathione in the airways of children with cystic
      fibrosis.
AB  - Glutathione is an important antioxidant in the lungs but its concentration is low
      in the airways of patients with cystic fibrosis. Whether this deficit occurs from
      an early age or how oxidative stress contributes to lowering glutathione is
      unknown. We measured glutathione, its oxidation products, myeloperoxidase, and
      biomarkers of hypochlorous acid in bronchoalveolar lavage from children with
      cystic fibrosis and disease controls using mass spectrometry and immunological
      techniques. The concentration of glutathione was lower in bronchoalveolar lavage
      from children with cystic fibrosis, whereas glutathione sulfonamide, a specific
      oxidation product of hypochlorous acid, was higher. Oxidised glutathione and
      glutathione sulfonamide correlated with myeloperoxidase and a biomarker of
      hypochlorous acid. The percentage of glutathione attached to proteins was higher
      in children with cystic fibrosis than controls. Pulmonary infections in cystic
      fibrosis resulted in lower levels of glutathione but higher levels of oxidised
      glutathione and glutathione sulfonamide in bronchoalveolar lavage. The
      concentration of glutathione is low in the airways of patients with cystic
      fibrosis from an early age. Increased oxidation of glutathione by hypochlorous
      acid and its attachment to proteins contribute to this deficiency. Therapies
      targeted against myeloperoxidase may boost antioxidant defence and slow the onset
      and progression of lung disease in cystic fibrosis. 

PMID- 24659543
TI  - The role of mepolizumab in atopic and nonatopic severe asthma with persistent
      eosinophilia.

PMID- 24659545
TI  - Association between sleep disordered breathing and aggressiveness markers of
      malignant cutaneous melanoma.
AB  - Some recent studies have shown an association between sleep disordered breathing
      (SDB) and cancer mortality and incidence but no study has focused on a specific
      type of cancer. The objective of this study was to analyse the relationship
      between the severity of SDB and factors related to cutaneous malignant melanoma
      (CMM) aggressiveness. We performed a multicentre observational study in 82
      consecutive patients diagnosed with CMM. 56 patients in whom melanoma
      measurements were available were finally included in the study. Melanoma
      measurements of aggressiveness included: tumour mitotic rate, Breslow index,
      presence of ulceration, stage of disease and growth rate of melanoma. A sleep
      study was performed in all the included patients. Multivariate analyses were used
      to examine the independent relationship between SDB severity (apnoea-hypopnea
      index (AHI) and nocturnal oxygen desaturation indexes (ODI3% and ODI4%)) and
      measures of CMM aggressiveness. 60.7% of patients had SDB (AHI >= 5) and 14.3%
      severe obstructive sleep apnoea (AHI >= 30). In fully adjusted multivariate
      analyses, AHI (OR 1.08, 95% CI 1.02-1.14), ODI3% (OR 1.08, 95% CI 1.02-1.11) and
      ODI4% (OR 1.1, 95% CI 1.02-1.2) were independently associated with an increased
      melanoma growth rate. Furthermore, AHI, ODI4% and ODI3% were significantly
      correlated with other aggressiveness factors of CMM, such as Breslow index,
      presence of ulceration and mitotic index. SDB severity markers are associated
      with some aggressiveness markers of CMM.

PMID- 24659546
TI  - The European initiative for quality management in lung cancer care.
AB  - Lung cancer is the commonest cause of cancer-related death worldwide and poses a
      significant respiratory disease burden. Little is known about the provision of
      lung cancer care across Europe. The overall aim of the Task Force was to
      investigate current practice in lung cancer care across Europe. The Task Force
      undertook four projects: 1) a narrative literature search on quality management
      of lung cancer; 2) a survey of national and local infrastructure for lung cancer
      care in Europe; 3) a benchmarking project on the quality of (inter)national lung
      cancer guidelines in Europe; and 4) a feasibility study of prospective data
      collection in a pan-European setting. There is little peer-reviewed literature on
      quality management in lung cancer care. The survey revealed important differences
      in the infrastructure of lung cancer care in Europe. The European guidelines that
      were assessed displayed wide variation in content and scope, as well as
      methodological quality but at the same time there was relevant duplication. The
      feasibility study demonstrated that it is, in principle, feasible to collect
      prospective demographic and clinical data on patients with lung cancer. Legal
      obligations vary among countries. The European Initiative for Quality Management
      in Lung Cancer Care has provided the first comprehensive snapshot of lung cancer
      care in Europe. 

PMID- 24659547
TI  - Double lung procurement from a donor supported by a left ventricular assist
      device.
AB  - Over the past several years, the selection criteria for marginal donor lungs have
      been extended. However, brain-dead patients with implanted mechanical circulatory
      support systems have not yet been considered as potential organ donors for lung
      transplantation. Our report presents the first successful procurement and
      transplantation of donor lungs from a patient supported by a left ventricular
      assist device. The procurement of the lungs demanded an extensive and careful
      anatomical preparation of the device, the heart, the lung and the mediastinum.
      The donor lungs were of good quality. The subsequent sequential bilateral lung
      transplantation was performed without complications. Postoperative course and
      follow-up were uneventful. This case demonstrates the feasibility of lung
      transplantations from organ donors supported by a mechanical circulatory support
      system. 

PMID- 24659548
TI  - Aortic valve repair: a ten-year single-centre experience?.
AB  - OBJECTIVES: Aortic valvuloplasty could represent an alternative to valve
      replacement resulting in optimal haemodynamic conditions, avoiding
      anticoagulation and allowing, in young people, normal aortic annulus growth. We
      analysed our results of aortic valve repair for incompetence due to leaflets and
      root pathology. METHODS: From January 2003 to January 2013, 235 patients affected
      by aortic valve regurgitation, pure or associated with aortic dilatation, were
      treated with a combination of the principal leaflet repair techniques and, when
      necessary, sparing procedures. Of these patients, 218 were considered eligible in
      this study. All of them were submitted to pre- and postoperative transthoracic
      echocardiography and pre- and post-repair transoesophageal echocardiography.
      Follow-up was achieved with periodic echocardiograms and clinical evaluations.
      RESULTS: Eight patients (3.40%) died before discharge. Median clinical and
      echocardiographic follow-up for all patients was 2.94 (1.41-5.41) years. Mean
      cross-clamping time was 101.94 +/- 40.22 min and mean hospital stay was 10 +/-
      6.69 days. Kaplan-Meier freedom from aortic regurgitation >2 and freedom from
      aortic valve replacement were, respectively, 92.9 +/- 2.8 and 94.5 +/- 2.5% at
      9.24 years: 6 patients (2.75%) were reoperated on with aortic valve replacement
      for severe aortic regurgitation. We also observed a good effect of aortic surgery
      on the left ventricle: the end-diastolic volume decreased from 137.89 +/- 50.23
      ml in the preop to 105.17 +/- 31.19 ml at follow-up. CONCLUSIONS: Aortic valve
      leaflet repair seems to be a good and feasible option for selected patients, both
      alone or associated with an aortic sparing technique concerning long-term
      results.

PMID- 24659549
TI  - Once-daily oral administration of cyclosporine in a lung transplant patient with
      a history of renal toxicity of calcineurin inhibitors.
AB  - Cyclosporine is usually administered orally in two divided doses every 12 h in
      transplant patients. However, some patients have difficulty in achieving
      therapeutic levels after transplantation. In fact, cyclosporine is reportedly
      administered once daily in renal and liver transplantation cases, but not in lung
      transplantation cases. We report a patient with a history of calcineurin
      inhibitor-induced renal toxicity who successfully underwent living-donor lobar
      lung transplantation (LDLLT) with the novel immunosuppressive strategy of once
      daily administration of cyclosporine. An 18-year old man with progressive
      respiratory insufficiency after bone marrow transplantation was referred to our
      hospital for lung transplantation. He had a history of renal toxicity due to
      calcineurin inhibitors. Based on his history of tacrolimus- and cyclosporine
      induced renal toxicity, we decided to initiate basiliximab as induction therapy,
      followed by once-daily cyclosporine administration to obtain high enough blood
      cyclosporine concentrations at 2 h post-dose (C2) and lowered trough blood
      concentrations (C0) for protection of renal function as maintenance therapy.
      LDLLT was successfully performed, and the postoperative course was uneventful and
      free of rejection episodes. Cyclosporine dosing was adjusted with intensive
      therapeutic drug monitoring of blood cyclosporine levels. One year after LDLLT,
      the patient is alive and well with no problems with daily life activities. 

PMID- 24659550
TI  - Holes in the heart: an atlas of intracardiac injuries following penetrating
      trauma.
AB  - OBJECTIVES: The extraordinarily high rate of penetrating heart injuries in South
      Africa provides a substantial denominator from which we derive a subset of
      patients with intracardiac lesions as a result of these injuries. The surgical
      literature, which consists largely of case reports and case series, describing
      various patterns of injury is dated and a review of management in the era of
      modern imaging and surgical techniques is warranted. METHODS: A retrospective
      observational chart review of all patients with intracardiac injuries following
      penetrating trauma who were referred to the Department of Cardiothoracic Surgery
      at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, during the 10
      year period between July 2003 and July 2013 was performed. The spectrum of
      pathology encountered included ventricular septal defects, valve apparatus
      lacerations, intracardiac fistulae, ventricular aneurysms and retained
      intracardiac missiles. RESULTS: Of the 17 patients, 10 required operative repair
      of the intracardiac lesions using cardiopulmonary bypass, with no early mortality
      noted. Seven patients were treated non-operatively, for reasons that varied from
      insignificant haemodynamic shunts to advanced human immunodeficiency virus (HIV)
      infection. The in-hospital mortality in this group consisted of 1 patient, who
      was moribund at presentation. CONCLUSIONS: The referral of patients for the
      repair of intracardiac injuries following penetrating cardiac trauma is often
      delayed. Symptoms of cardiac failure should be optimized medically prior to
      undertaking definitive surgical repair, thereby also allowing for detailed
      preoperative imaging to guide appropriate intervention. Utilizing standard
      principles of intracardiac shunt repair, as well as contemporary valve repair
      techniques, favourable surgical outcomes may be reproduced. Percutaneous catheter
      device techniques may prove useful in patients deemed unsuitable for surgical
      repair, such as patients with sternal wound sepsis.

PMID- 24659544
TI  - Management of patients with multidrug-resistant/extensively drug-resistant
      tuberculosis in Europe: a TBNET consensus statement.
AB  - The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)
      tuberculosis (TB) substantially challenges TB control, especially in the European
      Region of the World Health Organization, where the highest prevalence of MDR/XDR
      cases is reported. The current management of patients with MDR/XDR-TB is
      extremely complex for medical, social and public health systems. The treatment
      with currently available anti-TB therapies to achieve relapse-free cure is long
      and undermined by a high frequency of adverse drug events, suboptimal treatment
      adherence, high costs and low treatment success rates. Availability of optimal
      management for patients with MDR/XDR-TB is limited even in the European Region.
      In the absence of a preventive vaccine, more effective diagnostic tools and novel
      therapeutic interventions the control of MDR/XDR-TB will be extremely difficult.
      Despite recent scientific advances in MDR/XDR-TB care, decisions for the
      management of patients with MDR/XDR-TB and their contacts often rely on expert
      opinions, rather than on clinical evidence. This document summarises the current
      knowledge on the prevention, diagnosis and treatment of adults and children with
      MDR/XDR-TB and their contacts, and provides expert consensus recommendations on
      questions where scientific evidence is still lacking. 

PMID- 24659552
TI  - Does off-pump coronary artery bypass graft surgery have a beneficial effect on
      long-term mortality and morbidity compared with on-pump coronary artery bypass
      graft surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether off-pump coronary artery bypass
      grafting (CABG) surgery offered superior long-term outcomes compared with on-pump
      CABG surgery. Best evidence papers were considered to be those that had a follow
      up period of >=5 years, had >50 patients in either cohort, did not utilize
      concomitant interventions nor comprised low-risk, high-risk or sub-population
      groups. Where potential duplicate data sets from the same institution were
      likely, the more credible and recently published study was included. Two hundred
      and fifty-six papers were found as a result of the reported search, of which 16
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. The 16 studies
      comprised 4 prospective randomized controlled trials (RCTs), with the remaining
      12 retrospective, of which 8 were propensity-score matched. All 4 RCTs contained
      fewer than 450 participants. Two studies concluded with a survival advantage
      towards on-pump CABG: one, a large registry-based study, the Veterans Affairs,
      with >25 000 patients, and another, a propensity-matched retrospective study
      involving almost 8000 patients. The remaining 14 studies all provided evidence to
      suggest comparable long-term survival. In addition, all other long-term outcomes
      mentioned within these studies including angina recurrence, myocardial infarction
      heart failure, need for revascularization, stroke, graft patency, cognitive and
      quality of life showed similar results between the two groups. We conclude that
      off-pump CABG surgery may have similar or slightly reduced long-term survival
      compared with on-pump CABG surgery. Other long-term indicators such as
      cardiovascular or cerebrovascular events or neuro-psychological outcomes were
      similar between the two groups. Despite these conclusions, the evidence is
      limited by substantial variability in patient selection and study methods. The
      CORONARY (coronary artery bypass surgery off- or on-pump revascularization study)
      trial recently presented results, which showed no significant differences in
      composite outcomes at 1 year; it will be interesting to observe whether these
      comparable outcomes are maintained for a much longer time frame. 

PMID- 24659551
TI  - Temporary right ventricular support following left ventricle assist device
      implantation: a comparison of two techniques.
AB  - OBJECTIVES: Right ventricular failure (RVF) after implantation of left
      ventricular assist device (LVAD) is a dramatic complication. We compared
      retrospectively two techniques of temporary right ventricular support after LVAD
      (HeartMate II, Thoratec Corp, Pleasonton, CA, USA) implantation. METHODS: From 1
      January 2006 to 31 December 2012, 78 patients [mean age 52 +/- 1.34 years; 15
      women (19%)] received a HeartMate II at our institution. Among these, 18 patients
      (23%) suffered postimplant RVF treated by peripheral temporary right ventricular
      support. Aetiology of heart failure was ischaemic in 12 (67%) and dilated
      cardiomyopathy in 6 (33%) patients. The preimplant RV risk score averaged 5.1 +/-
      0.59. Ten patients were treated using a femorofemoral venoarterial extracorporeal
      life support (ECLS) and 8 patients were treated using extracorporeal membrane
      oxygenation as a right ventricular assist device (RVAD) established between a
      femoral vein and the pulmonary artery via a Dacron prosthesis (RVAD). RESULTS:
      Duration of RV support was 7.12 +/- 5.4 days and 9.57 +/- 3.5 days in
      venoarterial ECLS and vein and the pulmonary artery RVAD groups, respectively (P
      = 0.32). Three patients (17%) died while under RV support (venoarterial ECLS, n =
      2; and vein and the pulmonary artery RVAD, n = 1, P = 0.58). In the venoarterial
      ECLS group, 6 (60%) patients suffered major thromboembolic complications
      including thrombosis of the ECLS arterial line (n = 2), ischaemic stroke (n = 2)
      and thrombosis of the ascending aorta (n = 2). No major complication was observed
      in the vein and the pulmonary artery RVAD group (P = 0.01). RV support was
      successfully weaned in 8 (80%) patients of the venoarterial ECLS group and in 7
      (87.5%) of the vein and the pulmonary artery RVAD group (P = 0.58). The duration
      of postimplant intensive care unit stay was not different (respectively, 27.5 +/-
      18.7 days and 20.0 +/- 12.0 days; P = 0.38) between both groups. CONCLUSIONS:
      Temporary support of the failing RV after LVAD implantation using temporary vein
      and the pulmonary artery RVAD is a promising therapeutic option. This approach
      provides adequate LVAD pre- and afterload and is associated with significantly
      less thromboembolic complications.

PMID- 24659553
TI  - Investigation of cortisol levels in patients with anxiety disorders: a structured
      review.
AB  - Anxiety disorders are common and distressing medical conditions, which typically
      arise in adolescence or early adult life. They can persist for many years,
      reducing quality of life, limiting academic and occupational achievement, and
      being responsible for considerable economic pressures. Although a range of
      psychological and pharmacological treatments are available, their success is
      often limited, and many patients remain troubled by significant symptom-related
      disability for long periods. The detailed pathophysiology of each anxiety
      disorder is not established, and novel treatments that are based solely on
      current understanding of conventional neurotransmitter function are unlikely to
      be substantially more effective or better tolerated than current treatments.
      Investigations of hypothalamo-pituitary axis function across panic disorder,
      generalized anxiety disorder, specific phobias and social anxiety disorder have
      produced intriguing findings but not revealed a consistent pattern of endocrine
      disturbance, perhaps reflecting differences in methodology and the nature and
      size of the clinical samples. There is a persistent need for large, prospective
      studies using standardized methods for investigation and data analysis (164
      words). 

PMID- 24659555
TI  - Free jejunal flap transfer for pharyngoesophageal reconstruction in patients with
      intestinal malrotation: two case reports.
AB  - Intestinal malrotation results from failure of intestinal rotation and fixation
      during fetal life. We report two cases of esophageal reconstruction with free
      jejunal flaps following total laryngopharyngectomy of hypopharyngeal and cervical
      esophageal carcinoma in which intestinal malrotation was detected during the
      jejunal flap harvesting. In both cases, the ligament of Treitz was absent, and
      the laparotomy incision was thus extended to identify the jejunum. In case 1,
      harvesting an adequate length of the vascular pedicle of the flap was impossible
      because of the abnormal position of the pancreas; thus, a jejunal flap of maximal
      length was harvested for optimal pedicle positioning in the recipient site. In
      case 2, Ladd's ligament prohibited the release of the jejunum from the ascending
      colon and required its dissection. Both patients underwent successful
      reconstruction. When the ligament of Treitz is absent during jejunal flap
      harvesting, investing the whole bowel by extended laparotomy incision is
      recommended. When anatomical abnormality caused by intestinal malrotation is
      detected, releasing an adhesion of the jejunum from circumferential organs and
      identifying the adequate vascular pedicle of a jejunal flap are necessary. If
      harvesting the long vascular pedicle is impossible, a jejunal flap of maximal
      length should be harvested for optimal positioning for vascular anastomosis at
      the shortest distance in the recipient site.

PMID- 24659556
TI  - Development of a multiplex PCR system of 59 mitochondrial SNPs and genetic
      analysis in Chinese population.
AB  - The analysis of SNPs located on the mitochondrial DNA can provide information on
      maternal genetics. In the present study, a set of 59 SNPs were detected
      simultaneously using three multiplex allele-specific PCR and subsequent CE.
      Allele-specific primers were designed with different sizes to allow for
      specifically amplified paired alleles in the same reaction. An allelic ladder
      based on reference alleles was also created to maintain high-quality analysis
      standard. Samples from 400 unrelated individuals (200 of Han population and 200
      of Uyghur population, China) were successfully analyzed and assigned into 106
      relevant haplotypes, resulting in a discrimination power of 98.5%. The haplotype
      diversity was 0.978 for Han and 0.972 for Uyghur, respectively. Pairwise
      comparison of haplotype frequency distributions showed significant difference
      across ethnicities. These results suggest that the 59-SNP PCR system is a
      reliable, rapid, and economical method for large-scale screening of mitochondrial
      DNA variation, adding a new aspect for forensic individual identification.

PMID- 24659554
TI  - Interaction of stress, corticotropin-releasing factor, arginine vasopressin and
      behaviour.
AB  - Stress mediates the activation of a variety of systems ranging from inflammatory
      to behavioral responses. In this review we focus on two neuropeptide systems,
      corticotropin-releasing factor (CRF) and arginine vasopressin (AVP), and their
      roles in regulating stress responses. Both peptides have been demonstrated to be
      involved in anxiogenic and depressive effects, actions mediated in part through
      their regulation of the hypothalamic-pituitary-adrenal axis and the release of
      adrenocorticotropic hormone. Because of the depressive effects of CRF and AVP,
      drugs modifying the stress-associated detrimental actions of CRF and AVP are
      under development, particularly drugs antagonizing CRF and AVP receptors for
      therapy in depression. 

PMID- 24659557
TI  - Posttraumatic stress disorder and substance use disorder comorbidity among
      individuals with physical disabilities: findings from the National Comorbidity
      Survey Replication.
AB  - Co-occurring posttraumatic stress disorder (PTSD) and substance use disorder
      (SUD) affects multiple domains of functioning and presents complex challenges to
      recovery. Using data from the National Comorbidity Study Replication, a national
      epidemiological study of mental disorders (weighted N = 4,883), the current study
      sought to determine the prevalence of PTSD and SUD, the symptom presentation of
      these disorders, and help-seeking behaviors in relation to PTSD and SUD among
      individuals with physical disabilities (weighted n = 491; nondisabled weighted n
      = 4,392). Results indicated that individuals with physical disabilities exhibited
      higher rates of PTSD, SUD, and comorbid PTSD/SUD than nondisabled individuals.
      For example, they were 2.6 times more likely to meet criteria for lifetime PTSD,
      1.5 times more likely for lifetime SUD, and 3.6 times more likely for lifetime
      PTSD/SUD compared to their nondisabled peers. Additionally, individuals with
      physical disabilities endorsed more recent/severe PTSD symptoms and more lifetime
      trauma events than nondisabled individuals with an average of 5 different trauma
      events compared to 3 in the nondisabled group. No significant pattern of
      differences was noted for SUD symptom presentation, or for receipt of lifetime or
      past-year PTSD or SUD treatment. Implications of these findings and
      recommendations for future research are discussed. 

PMID- 24659560
TI  - Cell-penetrating peptides: A tool for effective delivery in gene-targeted
      therapies.
AB  - The current landscapes of novel therapeutic approaches rely mostly on gene
      targeted technologies, enabling to fight rare genomic diseases, from infections
      to cancer and hereditary diseases. Although, reaching the action-site for this
      novel treatments requires to deliver nucleic acids, or other macromolecules into
      cells, which may pose difficult tasks to pharmaceutical companies. To overcome
      this technological limitation, a wide variety of vectors have been developed in
      the past decades and have proven to be successful in delivering various
      therapeutics. Cell-penetrating peptides (CPP) have been one of the technologies
      widely studied and have been increasingly used to transport small RNA/DNA,
      plasmids, antibodies, and nanoparticles into cells. Despite the already proved
      huge potential that these peptide-based approaches may suggest, few advances have
      been put to pharmacological or clinical use. This review will describe the
      origin, development, and usage of CPP to deliver therapeutic agents into cells,
      with special emphasis on their current application to gene-therapies.
      Specifically, we will describe the current trials being conducted to treat
      cancer, gene disorders, and autoimmune diseases using CPP-based therapies. (c)
      2014 IUBMB Life, 66(3):182-194, 2014.

PMID- 24659562
TI  - Posttraumatic stress symptoms in breast cancer patients: temporal evolution,
      predictors, and mediation.
AB  - This study (N = 102 women) evaluated the time course of posttraumatic stress
      symptomatology (PTSS) at different stages of nonmetastastic cancer diagnosis and
      treatment: during treatment, at the end of treatment, and at a 6-12 months follow
      up. We also assessed the contribution of demographic, trait, and state predictors
      to PTSS, and coping processes as proximal mediators of the relation between Type
      C personality and PTSS. Results indicated that PTSS remained constant across all
      phases. There were significant correlations (range = .28 to .81) between PTSS and
      psychosocial variables and age, but not with other sociodemographic or medical
      factors. A linear growth curve model showed that hopelessness/helplessness (B =
      1.45) and Type C personality (B = 1.40) were the best predictors of PTSD
      symptomatology, followed by trait dissociation (B = 0.55), and the coping
      strategies of anxious preoccupation (B = 1.20), cognitive avoidance (B = 0.91),
      and symptoms of acute stress disorder (B = 0.19). A mediation model showed that
      the coping strategies of anxious preoccupation, cognitive avoidance, and
      helplessness/hopelessness mediated the relationship between Type C personality
      and PTSS during treatment, posttreatment, and follow-up. These results clarify
      the contribution of different predictors of PTSS and can help develop prevention
      programs. 

PMID- 24659561
TI  - Are there common familial influences for major depressive disorder and an
      overeating-binge eating dimension in both European American and African American
      female twins?
AB  - OBJECTIVE: Although prior studies have demonstrated that depression is associated
      with an overeating-binge eating dimension (OE-BE) phenotypically, little research
      has investigated whether familial factors contribute to the co-occurrence of
      these phenotypes, especially in community samples with multiple racial/ethnic
      groups. We examined the extent to which familial (i.e., genetic and shared
      environmental) influences overlapped between Major Depressive Disorder (MDD) and
      OE-BE in a population-based sample and whether these influences were similar
      across racial/ethnic groups. METHOD: Participants included 3,226 European
      American (EA) and 550 African American (AA) young adult women from the Missouri
      Adolescent Female Twin Study. An adaptation of the Semi-Structured Assessment for
      the Genetics of Alcoholism (SSAGA) was administered to assess lifetime DSM-IV MDD
      and OE-BE. Quantitative genetic modeling was used to estimate familial influences
      between both phenotypes; all models controlled for age. RESULTS: The best-fitting
      model, which combined racial/ethnic groups, found that additive genetic
      influences accounted for 44% (95% CI: 34%, 53%) of the MDD variance and 40% (25%,
      54%) for OE-BE, with the remaining variances due to non-shared environmental
      influences. Genetic overlap was substantial (rg  = .61 [.39, .85]); non-shared
      environmental influences on MDD and OE-BE overlapped weakly (re  = .26 [.09,
      .42]). DISCUSSION: Results suggest that common familial influences underlie MDD
      and OE-BE, and the magnitude of familial influences contributing to the
      comorbidity between MDD and OE-BE is similar between EA and AA women. If
      racial/ethnic differences truly exist, then larger sample sizes may be needed to
      fully elucidate familial risk for comorbid MDD and OE-BE across these groups.

PMID- 24659563
TI  - Different influence of Ti, PMMA, UHMWPE, and Co-Cr particles on peripheral blood
      monocytes during periprosthetic inflammation.
AB  - This study investigated cellular trafficking and inflammatory markers in
      orthopedic biomaterial particle-challenged human peripheral blood monocytes
      (PBMCs) using a murine immunodeficiency (SCID) model. Periprosthetic tissues from
      aseptic loosening patients were transplanted into muscles of SCID mice. PBMCs
      from the same patients were stimulated in vitro with Ti-6Al-4V, PMMA, UHMWPE, or
      Co-Cr particles for 3 days before administered intraperitoneally to the
      periprosthetic tissue-implanted mice. The xenografts were harvested 2 weeks later
      for histological and molecular analyses. Significant cell infiltration was
      obvious in the transplanted tissues from mice transfused with Ti-alloy, PMMA and
      UHMWPE-provoked PBMCs compared to controls, and UHMWPE-provoked PBMCs group
      accumulated significantly more cells among all groups. There were ubiquitous
      TRAP+ stained cells in all xenografts from particle-stimulated PBMCs mice.
      Immunohistochemical staining indicated that significantly more IL-1beta and TNF
      positive cells occurred in Ti and PMMA groups; while the UHMWPE group resulted in
      stronger positive MCP-1 and IL-6 stains. Polymerase chain reaction (PCR)
      confirmed overexpression of both IL-1beta and TNF in Ti and PMMA-stimulated
      groups; and more MIP-1alpha gene expression developed in the UHMWPE group.
      Overall, different type of orthopedic materials influenced the trafficking
      ability of particle-activated PBMCs which may depend on upregulation of various
      proinflammatory cytokines and chemokines.

PMID- 24659564
TI  - Characterization and in vitro differentiation potency of early-passage canine
      amnion- and umbilical cord-derived mesenchymal stem cells as related to
      gestational age.
AB  - Fetal adnexa are a non-controversial source of mesenchymal stem cells (MSCs) that
      have high plasticity, a high proliferation rate, and the ability to differentiate
      towards multiple lineages. MSC populations have been characterized for their
      stemness and differentiation capabilities; more recent work has focused on MSC
      selection and on establishing predictable elements to discriminate the cells with
      the most potential for regenerative medicine. In this study, we cytogenetically
      and molecularly characterized and followed the in vitro proliferation and
      differentiation potential of early-passage canine amniotic membrane MSCs (AM
      MSCs) and umbilical cord matrix MSCs (UCM-MSCs) isolated from fetuses at early
      (35-40 days) and late (45-55 days) gestational ages. We found that cells from
      both fetal gestational ages showed similar features. In all examined cell lines,
      the morphology of proliferating cells typically appeared fibroblast-like.
      Population doublings, passaged up to 10 times, increased significantly with
      passage number. In both cell types, cell viability and chromosomal number and
      structure were not affected by gestational age at early passages. Passage-3 AM-
      and UCM-MSCs from both gestational phases also expressed embryonic (POU5F1) and
      mesenchymal (CD29, CD44) stemness markers, whereas hematopoietic and
      histocompatibility markers were never found in any sample. Passage-3 cell
      populations of each cell type were also multipotential as they could
      differentiate into neurocytes and osteocytes, based on cell morphology, specific
      stains, and molecular analysis. These results indicated that MSCs retrieved from
      the UCM and AM in the early and late fetal phases of gestation could be used for
      canine regenerative medicine.

PMID- 24659565
TI  - Suppression of MicroRNA-203 improves survival of rat bone marrow mesenchymal stem
      cells through enhancing PI3K-induced cellular activation.
AB  - As a group of heterogeneous multipotent cells, mesenchymal stem cells (MSCs) have
      potential in treatment of a variety of clinical diseases. However, the low
      survival of the transplanted MSCs reduced their therapeutic effects. In this
      study, we revealed that rno-miR-203 suppressed activity and colony formation and
      enhanced apoptosis of the rat bone marrow-derived MSCs (BM-MSCs). Using
      bioinformatics analysis, we found a potential miR-203 binding site within rat
      phosphatidylinositol 3-kinase (PI3K) 3'UTR, and fluorescent reporter experiments
      validated the direct and negative regulation of PI3K expression by miR-203
      through this site. Ectopic expression of PI3K rescued BM-MSCs from depressed
      activity induced by miR-203, and suppression of PI3K attenuated the increased BM
      MSCs activity by miR-203 inhibitor treatment. Moreover, miR-203 blocking partly
      protected BM-MSCs from impairment caused by low nutrition. We conclude that
      inhibition of endogenous miR-203 elevated PI3K expression, which may strengthen
      PI3K/Akt pathway and promote BM-MSCs activity and survival. (c) 2014 IUBMB Life,
      66(3):220-227, 2014.

PMID- 24659566
TI  - Efficacy of long-term low-dose macrolide therapy in preventing early recurrence
      of nasal polyps after endoscopic sinus surgery.
AB  - BACKGROUND: This study assessed efficacy of clarithromycin "long-term" macrolide
      therapy as an adjunct to maintenance therapy with nasal corticosteroids to
      prevent recurrence of nasal polyps (NP) after functional endoscopic sinus surgery
      (FESS). METHODS: A total of 66 patients with chronic rhinosinusitis and bilateral
      NP were randomized into 3 study arms, 22 patients in each arm. After FESS,
      patients in the first and second groups were treated with clarithromycin 250
      mg/day for 12 and 24 weeks, respectively, whereas patients in the third group did
      not receive any clarithromycin. Patients in all 3 groups received maintenance
      therapy with mometasone furoate 400 MUg/day. Patient assessment was conducted
      before the surgery and 6, 12, and 24 weeks after surgery, using a visual analogue
      scale (VAS), 20-item SinoNasal Outcome Test (SNOT-20), acoustic rhinometry,
      rhinomanometry, saccharin transit time, nasal endoscopy, computed tomography (CT)
      of paranasal sinuses, and measurement of the level of eosinophil cationic protein
      (ECP) in their nasal secretions. RESULTS: The study confirmed efficacy of "long
      term" macrolide therapy, resulting in significant improvement of all parameters
      except acoustic rhinometry and VAS in both clarithromycin groups as compared to
      the control. Concentration of ECP in the nasal secretions increased dramatically
      after surgery, then returned to baseline levels after 12 and 24 weeks of
      treatment with clarithromycin. In the control group, ECP level continued to
      increase and was significantly higher at the endpoint. Both groups with
      clarithromycin showed significantly better endoscopic and CT scores than the
      control group at the end point. CONCLUSION: "Long-term" low-dose clarithromycin
      250 mg/day is able to control eosinophilic inflammation and prevent early relapse
      of NP after FESS.

PMID- 24659567
TI  - Coenzyme Q10 treatments influence the lifespan and key biochemical resistance
      systems in the honeybee, Apis mellifera.
AB  - Natural bioactive preparations that will boost apian resistance, aid body
      detoxification, or fight crucial bee diseases are in demand. Therefore, we
      examined the influence of coenzyme Q10 (CoQ10, 2,3-dimethoxy, 5-methyl, 6
      decaprenyl benzoquinone) treatment on honeybee lifespan, Nosema resistance, the
      activity/concentration of antioxidants, proteases and protease inhibitors, and
      biomarkers. CoQ10 slows age-related metabolic processes. Workers that consumed
      CoQ10 lived longer than untreated controls and were less infested with Nosema
      spp. Relative to controls, the CoQ10-treated workers had higher protein
      concentrations that increased with age but then they decreased in older bees.
      CoQ10 treatments increased the activities of antioxidant enzymes (superoxide
      dismutase, GPx, catalase, glutathione S-transferase), protease inhibitors,
      biomarkers (aspartate aminotransferase, alkaline phosphatase, alanine
      aminotransferase), the total antioxidant potential level, and concentrations of
      uric acid and creatinine. The activities of acidic, neutral, and alkaline
      proteases, and concentrations of albumin and urea were lower in the bees that
      were administered CoQ10. CoQ10 could be taken into consideration as a natural
      diet supplement in early spring before pollen sources become available in the
      temperate Central European climate. A response to CoQ10 administration that is
      similar to mammals supports our view that Apis mellifera is a model organism for
      biochemical gerontology. 

PMID- 24659568
TI  - Surface modification on polycaprolactone electrospun mesh and human decalcified
      bone scaffold with synovium-derived mesenchymal stem cells-affinity peptide for
      tissue engineering.
AB  - Synovium-derived mesenchymal stem cells (SMSC) have been studied for over a
      decade since first being successfully isolated in 2001. These cells demonstrate
      the most promising therapeutic efficacy for musculoskeletal regeneration of the
      MSC family, particularly for cartilage regeneration. However, the mobilization
      and transfer of MSCs to defective or damaged tissues and organs in vivo with high
      accuracy and efficiency has been a major problem in tissue engineering (TE). In
      the present study, we identified a seven amino acid peptide sequence [SMSCs
      affinity peptide (LTHPRWP; L7)] through phage display technology that has a high
      specific affinity to SMSCs. Our analysis suggested that L7 efficiently and
      specifically interacted with SMSCs without any species specificity. Thereafter,
      L7 was covalently conjugated onto both polycaprolactone (PCL) electrospun meshes
      and human decalcified bone scaffolds (hDBSc) to investigate its TE applications.
      After 24 h coculture with human SMSCs (hSMSCs), L7-conjugated PCL electrospun
      meshes had significantly more adherent hSMSCs than the control group, and the
      cells expanded well. Similar results were obtained using hDBSs. These results
      suggest that the novel L7 peptide sequence has a high specific affinity to SMSCs.
      Covalently conjugating this peptide to either artificial polymer material (PCL
      mesh) or natural material (hDBS) significantly enhances the adhesion of SMSCs.
      This method is applicable to a wide range of potential SMSC-based TE
      applications, particularly to cartilage regeneration, via surface modification on
      various type of materials.

PMID- 24659569
TI  - Analysis of testicular-internal spermatic vein variation and the recreation of
      varicocoele in a Sprague-Dawley rat model.
AB  - Many laboratories tried to recreate the varicocoele model have met with varied
      success. To recreate a consistent varicocoele model by exploring the anatomic
      variability of the testicular-spermatic venous system in Sprague-Dawley (SD)
      rats. Seventy-two sexually mature SD male rats were randomly divided into three
      groups containing 24 rats per group. Partial ligation of the left renal vein and
      internal spermatic vein (ISV) communicating branches to common iliac vein and ISV
      communicating branches ligation (RVISVCBCIV) or partial ligation of the left
      renal vein and ISV communicating branches ligation (RVISVCB). The results showed
      that the mean diameter of the left ISV was significantly increased in the
      RVISVCBCIV group compared with the control and RVISVCB groups (p < 0.001). Using
      ISV as the reference, the sensitivity of varicocoele was 71.43%, and the
      specificity was 80%. In addition, the positive predictive value was 83.33%, and
      the negative predictive value was 66.67%. Sperm count, motility, Johnsen score
      and the spermatogenic cell density were lower in the RVISVCBCIV group compared
      with the control (p < 0.01). The apoptotic index was higher in the RVISVCBCIV
      group compared with control groups (p < 0.01). The RVISVCBCIV provides a more
      effective method for establishing a varicocoele-induced model.

PMID- 24659570
TI  - Predictors and variability of repeat measurements of urinary phenols and parabens
      in a cohort of Shanghai women and men.
AB  - BACKGROUND: Exposure to certain phenols is ubiquitous because of their use in
      many consumer and personal care products. However, predictors of exposure have
      not been well characterized in most populations. OBJECTIVES: We sought to
      identify predictors of exposure and to assess the reproducibility of phenol
      concentrations across serial spot urine samples among Chinese adults. METHODS: We
      measured 2,4-dichlorophenol, 2,5-dichlorophenol, butyl paraben, methyl paraben,
      propyl paraben, benzophenone-3, bisphenol A, and triclosan in urine collected
      during 1997-2006 from 50 participants of the Shanghai Women's Health Study cohort
      and during 2002-2006 from 50 participants of the Shanghai Men's Health Study
      cohort. We investigated predictors of concentrations using the Satterthwaite t
      test, and assessed reproducibility among serial samples using intraclass
      correlation coefficients (ICCs) and Spearman correlation coefficients (SCCs).
      RESULTS: Creatinine-corrected phenol concentrations were generally higher among
      women than men. Participants who had taken medicine within the previous 24 hr had
      higher concentrations of propyl paraben. Cigarette smoking was associated with
      lower concentrations of propyl and methyl parabens among men. Bottled water
      consumption was associated with higher bisphenol A, 2,4-dichlorophenol, and 2,5
      dichlorophenol concentrations among women. Among men, reproducibility across
      serial samples was moderate for 2,4-dichlorophenol and 2,5-dichlorophenol (ICC =
      0.54-0.60, SCC = 0.43-0.56), but lower for other analytes (ICC = 0.20-0.29).
      Reproducibility among women was low (ICC = 0.13-0.39), but increased when
      restricted to morning-only urine samples. CONCLUSIONS: Among these 100 Shanghai
      residents, urinary phenol concentrations varied by sex, smoking, and consumption
      of bottled water. Our results suggest that a single urine sample may be adequate
      for ranking exposure to the precursors of 2,4-dichlorophenol and 2,5
      dichlorophenol among men and, under certain circumstances, among women.

PMID- 24659571
TI  - Accelerated human cardiac diffusion tensor imaging using simultaneous multislice
      imaging.
AB  - PURPOSE: To demonstrate the feasibility of accelerating measurements of cardiac
      fiber structure using simultaneous multislice (SMS) imaging. METHODS: SMS
      excitation with a blipped controlled aliasing (CAIPI) readout was incorporated
      into a diffusion-encoded stimulated echo pulse sequence to obtain diffusion
      measurements in three separate slices of the heart (8-mm thickness, 12-mm gap). A
      novel image entropy-based method for removing image ghosts in blipped CAIPI
      acquisitions is also introduced that enables SMS imaging of closely spaced slices
      in the heart. RESULTS: The average retained signal-to-noise ratio (SNR) using
      this acquisition scheme is 70% +/- 5%, higher than the standard 1/3 = 57% SNR
      penalty with three-fold acceleration. No significant difference was observed in
      the apparent diffusion coefficient and helix angle diffusion parameters between a
      time-equivalent conventional single-slice scan and the three-fold accelerated SMS
      acquisition. A 10% mean bias was observed in fractional anisotropy between single
      slice and SMS acquisitions. CONCLUSION: The new sequence was used to obtain high
      quality diffusion measurements in three closely spaced cardiac slices in a
      clinically feasible nine breath-hold examination. The accelerated multiband
      sequence is anticipated to improve quantitative measurements of cardiac
      microstructure by reducing the number of breath-holds required for the scan,
      making it practical to incorporate diffusion tensor measurements within a
      comprehensive clinical examination.

PMID- 24659572
TI  - New insights into roles of intermediate filament phosphorylation and progeria
      pathogenesis.
AB  - Intermediate filaments (IFs) form one of the major cytoskeletal systems in the
      cytoplasm or beneath the nuclear membrane. Because of their insoluble nature,
      cellular IFs had been considered to be stable for a long time. The discovery that
      a purified protein kinase phosphorylated a purified IF protein and in turn
      induced the disassembly of IF structure in vitro led to the novel concept of
      dynamic IF regulation. Since then, a variety of protein kinases have been
      identified to phosphorylate IF proteins such as vimentin in a spatiotemporal
      regulated manner. A series of studies using cultured cells have demonstrated that
      preventing IF phosphorylation during mitosis inhibits cytokinesis by the
      retention of an IF bridge-like structure (IF-bridge) connecting the two daughter
      cells. Knock-in mice expressing phosphodeficient vimentin variants developed
      binucleation/aneuploidy in lens epithelial cells, which promoted microophthalmia
      and lens cataract. Therefore, mitotic phosphorylation of vimentin is of great
      importance in the completion of cytokinesis, the impairment of which promotes
      chromosomal instability and premature aging. (c) 2014 IUBMB Life, 66(3):195-200,
      2014.

PMID- 24659573
TI  - Regulation of the polyamine metabolic pathway in the endometrium of cows during
      early diestrus.
AB  - The timing and magnitude of exposure to preovulatory estradiol followed by post
      ovulatory progesterone (periovulatory endocrine milieu) in cattle modulate
      endometrial gene expression, histotroph composition, and conceptus development,
      but the mechanisms underlying this regulation remain unknown. Using an
      experimental model based on the modulation of follicle growth, this work aimed to
      evaluate if the polyamine metabolic pathway is regulated by the periovulatory
      endocrine milieu. Nelore cows were manipulated to ovulate small (n = 15) or large
      (n = 15) follicles, then the profiles of polyamines and their synthetic enzymes
      were compared between groups. Transcripts for the enzymes of this pathway,
      ornithine decarboxylase 1 (ODC1; the rate-limiting enzyme in polyamine
      biosynthesis) protein quantification, adenosylmethionine decarboxylase 1 (AMD1)
      protein immunolocalization, and concentrations of the different polyamines
      (putrescine, spermidine, and spermine) were respectively quantified by
      quantitative reverse-transcriptase PCR, immunoblotting, immunohistochemistry, and
      gas chromatography-mass spectrometry in both the endometrium and uterine
      flushing. No differences in gene and protein expression or concentration of
      polyamines were observed between groups. There were significant correlations
      between the relative abundance of ODC1 and spermidine/spermine N1
      acetyltransferase 1 (SAT1) transcripts as well as between antizyme inhibitor 1
      (AZIN1) and adenosylmethionine decarboxylase 1 (AMD1) transcripts. In conclusion,
      our results show that the polyamine metabolic pathway is present and functional,
      but not regulated by the periovulatory endocrine milieu in the bovine
      endometrium.

PMID- 24659574
TI  - Spray-assisted layer-by-layer assembly on hyaluronic acid scaffolds for skin
      tissue engineering.
AB  - Tissue engineering approaches for the development of a single epidermal-dermal
      scaffold to treat full-thickness skin defects have been limited by difficulties
      in the fabrication of a bilayer scaffold combining the specific properties of the
      epidermis and the dermis. Here we present an innovative approach to developing a
      scaffold that holds promise for skin tissue engineering. We utilize the spray
      assisted layer-by-layer assembly technique to deposit a polyelectrolyte
      multilayer film composed of hyaluronic acid and poly-L-lysine (the epidermal
      component) on a porous hyaluronic acid scaffold (the dermal component), in a
      rapid and controlled manner. The multilayer film promotes cell adhesion,
      contributing to regeneration of the epidermal barrier functions of skin. While
      human keratinocytes attached and proliferated on the coated porous scaffolds,
      they did not invade the porous dermal component, thus leaving room for seeding of
      relevant fibroblast cell types in this scaffold. This scaffold therefore holds
      promise for co-culture of different cells, which may be useful for treatment of
      full-thickness skin defects as well as other tissue engineering applications.

PMID- 24659575
TI  - Transcriptional regulators TRIM28, SETDB1, and TP53 are aberrantly expressed in
      porcine embryos produced by in vitro fertilization in comparison to in vivo- and
      somatic-cell nuclear transfer-derived embryos.
AB  - In vitro embryo production is important for research in animal reproduction,
      embryo transfer, transgenics, and cloning. Yet, in vitro-fertilized (IVF) embryos
      are generally developmentally delayed and are inferior to in vivo-derived (IVV)
      embryos; this discrepancy is likely a result of aberrant gene expression.
      Transcription of three genes implicated to be important in normal preimplantation
      embryo development, TRIM28, SETDB1, and TP53, was determined by quanitative PCR
      in IVF, somatic-cell nuclear transfer (SCNT), parthenogenetic, and IVV porcine
      oocytes and embryos. There was no difference in TRIM28 or SETDB1 abundance
      between oocytes matured in vitro versus in vivo (P > 0.05), whereas TP53 levels
      were higher in in vitro-matured oocytes. TRIM28 increased from metaphase-II
      oocytes to the 4-cell and blastocyst stages in IVF embryos, whereas IVV embryos
      showed a reduction in TRIM28 abundance from maturation throughout development.
      The relative abundance of TP53 increased by the blastocyst stage in all treatment
      groups, but was higher in IVF embryos compared to IVV and SCNT embryos. In
      contrast, SETDB1 transcript levels decreased from the 2-cell to blastocyst stage
      in all treatments. For each gene analyzed, SCNT embryos of both hard-to-clone and
      easy-to-clone cell lines were more comparable to IVV than IVF embryos. Knockdown
      of TRIM28 also had no effect on blastocyst development or expression of SETDB1 or
      TP53. Thus, TRIM28, SETDB1, and TP53 are dynamically expressed in porcine oocytes
      and embryos. Furthermore, TRIM28 and TP53 abundances in IVV and SCNT embryos are
      similar, but different from quantities in IVF embryos.

PMID- 24659576
TI  - Water distribution system deficiencies and gastrointestinal illness: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Water distribution systems are vulnerable to performance deficiencies
      that can cause (re)contamination of treated water and plausibly lead to increased
      risk of gastrointestinal illness (GII) in consumers. OBJECTIVES: It is well
      established that large system disruptions in piped water networks can cause GII
      outbreaks. We hypothesized that routine network problems can also contribute to
      background levels of waterborne illness and conducted a systematic review and
      meta-analysis to assess the impact of distribution system deficiencies on endemic
      GII. METHODS: We reviewed published studies that compared direct tap water
      consumption to consumption of tap water re-treated at the point of use (POU) and
      studies of specific system deficiencies such as breach of physical or hydraulic
      pipe integrity and lack of disinfectant residual. RESULTS: In settings with
      network malfunction, consumers of tap water versus POU-treated water had
      increased GII [incidence density ratio (IDR) = 1.34; 95% CI: 1.00, 1.79]. The
      subset of nonblinded studies showed a significant association between GII and tap
      water versus POU-treated water consumption (IDR = 1.52; 95% CI: 1.05, 2.20), but
      there was no association based on studies that blinded participants to their POU
      water treatment status (IDR = 0.98; 95% CI: 0.90, 1.08). Among studies focusing
      on specific network deficiencies, GII was associated with temporary water outages
      (relative risk = 3.26; 95% CI: 1.48, 7.19) as well as chronic outages in
      intermittently operated distribution systems (odds ratio = 1.61; 95% CI: 1.26,
      2.07). CONCLUSIONS: Tap water consumption is associated with GII in
      malfunctioning distribution networks. System deficiencies such as water outages
      also are associated with increased GII, suggesting a potential health risk for
      consumers served by piped water networks.

PMID- 24659577
TI  - Biochemical and kinetic characterization of xylulose 5-phosphate/fructose 6
      phosphate phosphoketolase 2 (Xfp2) from Cryptococcus neoformans.
AB  - Xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp), previously
      thought to be present only in bacteria but recently found in fungi, catalyzes the
      formation of acetyl phosphate from xylulose 5-phosphate or fructose 6-phosphate.
      Here, we describe the first biochemical and kinetic characterization of a
      eukaryotic Xfp, from the opportunistic fungal pathogen Cryptococcus neoformans,
      which has two XFP genes (designated XFP1 and XFP2). Our kinetic characterization
      of C. neoformans Xfp2 indicated the existence of both substrate cooperativity for
      all three substrates and allosteric regulation through the binding of effector
      molecules at sites separate from the active site. Prior to this study, Xfp
      enzymes from two bacterial genera had been characterized and were determined to
      follow Michaelis-Menten kinetics. C. neoformans Xfp2 is inhibited by ATP,
      phosphoenolpyruvate (PEP), and oxaloacetic acid (OAA) and activated by AMP. ATP
      is the strongest inhibitor, with a half-maximal inhibitory concentration (IC50)
      of 0.6 mM. PEP and OAA were found to share the same or have overlapping
      allosteric binding sites, while ATP binds at a separate site. AMP acts as a very
      potent activator; as little as 20 MUM AMP is capable of increasing Xfp2 activity
      by 24.8% +/- 1.0% (mean +/- standard error of the mean), while 50 MUM prevented
      inhibition caused by 0.6 mM ATP. AMP and PEP/OAA operated independently, with AMP
      activating Xfp2 and PEP/OAA inhibiting the activated enzyme. This study provides
      valuable insight into the metabolic role of Xfp within fungi, specifically the
      fungal pathogen Cryptococcus neoformans, and suggests that at least some Xfps
      display substrate cooperative binding and allosteric regulation. 

PMID- 24659578
TI  - UPC2 is universally essential for azole antifungal resistance in Candida
      albicans.
AB  - In Candida albicans, the transcription factor Upc2 is central to the regulation
      of ergosterol biosynthesis. UPC2-activating mutations contribute to azole
      resistance, whereas disruption increases azole susceptibility. In the present
      study, we investigated the relationship of UPC2 to fluconazole susceptibility,
      particularly in azole-resistant strains. In addition to the reduced fluconazole
      MIC previously observed with UPC2 disruption, we observed a lower minimum
      fungicidal concentration (MFC) for a upc2Delta/Delta mutant than for its azole
      susceptible parent, SC5314. Moreover, the upc2Delta/Delta mutant was unable to
      grow on a solid medium containing 10 MUg/ml fluconazole and exhibited increased
      susceptibility and a clear zone of inhibition by Etest. Time-kill analysis showed
      higher fungistatic activity against the upc2Delta/Delta mutant than against
      SC5314. UPC2 disruption in strains carrying specific resistance mutations also
      resulted in reduced MICs and MFCs. UPC2 disruption in a highly azole resistant
      clinical isolate containing multiple resistance mechanisms likewise resulted in a
      reduced MIC and MFC. This mutant was unable to grow on a solid medium containing
      10 MUg/ml fluconazole and exhibited increased susceptibility and a clear zone of
      inhibition by Etest. Time-kill analysis showed increased fungistatic activity
      against the upc2Delta/Delta mutant in the resistant background. Microarray
      analysis showed attenuated induction by fluconazole of genes involved in sterol
      biosynthesis, iron transport, or iron homeostasis in the absence of UPC2. Taken
      together, these data demonstrate that the UPC2 transcriptional network is
      universally essential for azole resistance in C. albicans and represents an
      attractive target for enhancing azole antifungal activity. 

PMID- 24659579
TI  - Low INSL3 in Klinefelter syndrome is related to osteocalcin, testosterone
      treatment and body composition, as well as measures of the hypothalamic-pituitary
      gonadal axis.
AB  - Klinefelter syndrome (KS) is characterized by infertility and hypogonadism
      associated with increased prevalence of osteoporosis, diabetes and metabolic
      syndrome. Insulin-like factor 3 (INSL3) is produced in the Leydig cells. INSL3
      has been suggested to play a role in bone health. Here, we studied INSL3 in
      relation to bone markers, body composition, the metabolic syndrome and diabetes.
      This was a case-control study. Sex hormones, anthropometric measures, vitamin D
      metabolites, parathyroid hormone, growth factors, muscle strength, maximal oxygen
      consumption and BMD were measured. We included 70 adult KS patients and 71 age
      matched controls. INSL3 was lower in testosterone-treated KS compared with
      untreated KS. Correlation analyses showed a positive correlation between INSL3
      and osteocalcin among KS, but not in controls; a significant positive correlation
      between INSL3 and testosterone in controls and in untreated KS, but not in
      treated KS men. Among controls a negative correlation was found between INSL3 and
      lipids, and glucose, but not in KS. HOMA2-B and impaired fasting glycaemia was
      positively correlated with INSL3 in controls. Among KS males we found a negative
      correlation between INSL3 and BMI, weight and waist/hip ratio, as well as
      positive correlations between INSL3 and FSH, LH, SHBG and testis volume.
      Multivariate analyses showed that age, testosterone and HDL cholesterol were the
      principal independent variables among healthy controls, whereas the determinants
      of INSL3 concentration among KS were age, LH, current testosterone treatment and
      testicular volume. INSL3 in KS is influenced by testosterone treatment and INSL3
      is correlated with measures of bone metabolism, body composition and the
      metabolic syndrome. This may suggest that low INSL3 concentration is related to
      the pathogenesis behind an unfavourable change in body composition and bone
      metabolism among KS patients.

PMID- 24659580
TI  - Monitoring the aquatic toxicity of mosquito vector control spray pesticides to
      freshwater receiving waters.
AB  - Pesticides are applied to state and local waterways in California to control
      insects such as mosquitoes, which are known to serve as a vector for West Nile
      Virus infection of humans. The California State Water Resources Control Board
      adopted a National Pollutant Discharge Elimination System General Permit to
      address the discharge to waters of the United States of pesticides resulting from
      adult and larval mosquito control. Because pesticides used in spray activities
      have the potential to cause toxicity to nontarget organisms in receiving waters,
      the current study was designed to determine whether toxicity testing provides
      additional, useful environmental risk information beyond chemical analysis in
      monitoring spray pesticide applications. Monitoring included a combination of
      aquatic toxicity tests and chemical analyses of receiving waters from
      agricultural, urban, and wetland habitats. The active ingredients monitored
      included the organophosphate pesticides malathion and naled, the pyrethroid
      pesticides etofenprox, permethrin, and sumithrin, pyrethrins, and piperonyl
      butoxide (PBO). Approximately 15% of the postapplication water samples were
      significantly toxic. Toxicity of half of these samples was attributed to the
      naled breakdown product dichlorvos. Toxicity of 2 other water samples likely
      occurred when PBO synergized the effects of pyrethroid pesticides that were
      likely present in the receiving system. Four of 43 postapplication sediment
      samples were significantly more toxic than their corresponding pre-application
      samples, but none of the observed toxicity was attributed to the application
      events. These results indicate that many of the spray pesticides used for adult
      mosquito control do not pose significant acute toxicity risk to invertebrates in
      receiving systems. In the case of naled in water, analysis of only the active
      ingredient underestimated potential impacts to the receiving system, because
      toxicity was attributed to the breakdown product, dichlorvos. Toxicity testing
      can provide useful risk information about unidentified, unmeasured toxicants or
      mixtures of toxicants. In this case, toxicity testing provided information that
      could lead to the inclusion of dichlorvos monitoring as a permit requirement.

PMID- 24659581
TI  - Performance of the resolute zotarolimus-eluting stent in small vessels.
AB  - BACKGROUND: Drug eluting stents for the treatment of small vessel coronary artery
      disease have traditionally yielded inferior clinical outcomes compared to the use
      of DES in large vessels. The benefit of the second-generation Resolute
      zotarolimus-eluting stent (R-ZES) in small vessels was examined. METHODS: Two
      year clinical outcomes from five combined R-ZES studies were compared between
      patients with small (reference vessel diameter [RVD] <=2.5 mm; n = 1,956) and
      large (RVD >2.5 mm; n = 3174) vessels. RESULTS: Despite a higher incidence of
      comorbidities in the small vessel group, there was no significant difference in
      target lesion failure (TLF) (10.1% vs. 8.7%; P = 0.54) at 2 years. When the
      subgroup of patients with diabetes was examined (n = 1,553) there was no
      significant difference in 2-year TLF in small compared to large vessels (11.2%
      vs. 11.1%; P = 0.17). Similarly, within the small vessel cohort, no significant
      difference was seen regarding TLF at 2 years between people with and without
      diabetes (11.2% vs 9.6%; P = 0.28). CONCLUSION: When used for the treatment of
      small vessels, the R-ZES appears to provide acceptable clinical results at 2
      years when compared to its performance in large vessels.

PMID- 24659582
TI  - Commentary: mental health and public health.

PMID- 24659583
TI  - Psychiatric epidemiology and global mental health: joining forces.

PMID- 24659584
TI  - Increased carriage of macrolide-resistant fecal E. coli following mass
      distribution of azithromycin for trachoma control.
AB  - BACKGROUND: Mass drug treatment with azithromycin (MDA) is part of the WHO
      endorsed 'SAFE' strategy for trachoma control in endemic communities. MDA has
      been associated with reduced trachoma prevalence and short-term reductions in
      other bacterial infections, but can also lead to increased circulation of
      macrolide-resistant bacteria. METHODS: We prospectively monitored macrolide
      resistance in fecal E. coli collected from young children participating in the
      PRET+ Study in rural Tanzania. MDA was administered in four villages with >10%
      trachoma prevalence. Four nearby communities with lower trachoma prevalence
      served as controls. Rectal swabs were collected during cross-sectional surveys
      performed at baseline, 1, 3 and 6 months after MDA. Fecal E. coli isolates were
      screened for macrolide susceptibility using disc diffusion and minimum inhibitory
      concentration methods. Cross-sectional and longitudinal differences in resistance
      prevalence by MDA exposure were compared using t-tests and logistic regression.
      RESULTS: There was no difference in the proportion of individuals carrying
      azithromycin-resistant E. coli at baseline (0.21 vs. 0.16, P > 0.05).
      Azithromycin resistance carriage prevalence remained stable over follow-up in non
      MDA villages but increased sharply in MDA villages (0.61 at 1 month, 0.42 at 3
      months and 0.31 at 6 months). MDA exposure was highly associated with
      azithromycin resistance carriage at 1 month post-MDA (OR 15.27, P < 0.001) and
      subsequent surveys. Younger age and recent diarrhoea were also associated with
      increased odds of resistance (P < 0.01). CONCLUSIONS: MDA resulted in
      significantly increased prevalence of macrolide resistance in E. coli. Although
      MDA is effective for trachoma elimination, it has costs; it is essential to
      monitor antimicrobial resistance following MDA.

PMID- 24659585
TI  - Tetrachloroethylene exposure and bladder cancer risk: a meta-analysis of dry
      cleaning-worker studies.
AB  - BACKGROUND: In 2012, the International Agency for Research on Cancer classified
      tetrachloroethylene, used in the production of chemicals and the primary solvent
      used in dry cleaning, as "probably carcinogenic to humans" based on limited
      evidence of an increased risk of bladder cancer in dry cleaners. OBJECTIVES: We
      assessed the epidemiological evidence for the association between
      tetrachloroethylene exposure and bladder cancer from published studies estimating
      occupational exposure to tetrachloroethylene or in workers in the dry-cleaning
      industry. METHODS: Random-effects meta-analyses were carried out separately for
      occupational exposure to tetrachloroethylene and employment as a dry cleaner. We
      qualitatively summarized exposure-response data because of the limited number of
      studies available. RESULTS: The meta-relative risk (mRR) among
      tetrachloroethylene-exposed workers was 1.08 (95% CI: 0.82, 1.42; three studies;
      463 exposed cases). For employment as a dry cleaner, the overall mRR was 1.47
      (95% CI: 1.16, 1.85; seven studies; 139 exposed cases), and for smoking-adjusted
      studies, the mRR was 1.50 (95% CI: 0.80, 2.84; 4 case-control studies).
      CONCLUSIONS: Our meta-analysis demonstrates an increased risk of bladder cancer
      in dry cleaners, reported in both cohort and case-control studies, and some
      evidence for an exposure-response relationship. Although dry cleaners incur mixed
      exposures, tetrachloroethylene could be responsible for the excess risk of
      bladder cancer because it is the primary solvent used and it is the only chemical
      commonly used by dry cleaners that is currently identified as a potential bladder
      carcinogen. Relatively crude approaches in exposure assessment in the studies of
      "tetrachloroethylene-exposed workers" may have attenuated the relative risks.

PMID- 24659587
TI  - Patients with cancer on the ICU: time for optimism.

PMID- 24659586
TI  - Melatonin in testes of infertile men: evidence for anti-proliferative and anti
      oxidant effects on local macrophage and mast cell populations.
AB  - Melatonin acting through the hypothalamus and pituitary regulates testicular
      function. In addition, direct actions of melatonin at the testicular level have
      been recently suggested. We have described that melatonin inhibits androgen
      production in hamster Leydig cells via melatonin subtype 1a (mel1a) receptors and
      the local corticotrophin-releasing hormone (CRH) system. The initial events of
      the melatonin/CRH signalling pathway have also been established. Melatonin and
      all components of the melatonergic/CRH system were also detected in Leydig cells
      of infertile men. This study attempted to search for additional targets of
      melatonin in the human testis, and to investigate the effects of melatonin on
      proliferation and the oxidative state in these novel target cells. To this aim,
      evaluation of human testicular biopsies of patients suffering from
      hypospermatogenesis or Sertoli cell only syndrome and cell culture studies were
      performed. Melatonergic receptors were found in macrophages (MACs) and mast cells
      (MCs) of the human testis. In biopsies of patients suffering idiopathic
      infertility, melatonin testicular concentrations were negatively correlated with
      MAC number per mm(2) and TNFalpha, IL1beta and COX2 expression, but positively
      correlated with the expression of the anti-oxidant enzymes SOD1, peroxiredoxin 1
      and catalase. Melatonin inhibited proliferation and the expression of pro
      inflammatory cytokines and cyclooxygenase 2 (COX2) in both the human non
      testicular THP-1 MAC cell line and primary cell cultures of hamster testicular
      MACs. In the human HMC-1 MC line, melatonin increased the expression of anti
      oxidant enzymes and decreased reactive oxygen species (ROS) generation. The
      results reveal new testicular targets of melatonin and describe anti
      proliferative and anti-inflammatory effects of this hormone on testicular MACs.
      Furthermore, melatonin might provide protective effects against oxidative stress
      in testicular MCs.

PMID- 24659588
TI  - Steroid diabetes: from mechanism to treatment?
AB  - Glucocorticoids (GCs) are frequently prescribed anti-inflammatory and
      immunosuppressive drugs. In addition to their beneficial effects on disease
      activity, GCs have an extensive side effect profile, including adverse effects on
      metabolism resulting in the development of glucose intolerance and overt
      diabetes. Recent developments have led to renewed interest in the mechanisms
      underlying these diabetogenic effects of GCs. First, dissociated glucocorticoid
      receptor (GR) agonists were developed which are designed to segregate the anti
      inflammatory and metabolic actions of GCs, potentially rendering compounds with a
      higher therapeutic index. Second, at present, 11-beta hydroxysteroid
      dehydrogenase type-1 inhibitors are under development. These compounds may lower
      tissue GC concentrations by inhibiting cortisone to cortisol conversion and are
      being evaluated in clinical trials as a novel treatment modality for the
      metabolic syndrome. Here, we provide an up-to-date overview of the current
      insights regarding the mechanisms responsible for the adverse metabolic effects
      of GCs that may lead to steroid diabetes. Particularly, we will focus on GC
      related induction of insulin resistance and pancreatic islet-cell dysfunction.
      Finally, we will discuss how increased knowledge concerning the pathophysiology
      of steroid diabetes may result in improved treatment strategies. 

PMID- 24659589
TI  - Ethylene glycol or methanol intoxication: which antidote should be used,
      fomepizole or ethanol?
AB  - Ethylene glycol (EG) and methanol poisoning can cause life-threatening
      complications. Toxicity of EG and methanol is related to the production of toxic
      metabolites by the enzyme alcohol dehydrogenase (ADH), which can lead to
      metabolic acidosis, renal failure (in EG poisoning), blindness (in methanol
      poisoning) and death. Therapy consists of general supportive care (e.g.
      intravenous fluids, correction of electrolytes and acidaemia), the use of
      antidotes and haemodialysis. Haemodialysis is considered a key element in the
      treatment of severe EG and methanol intoxication and is aimed at removing both
      the parent compound and its toxic metabolites, reducing the duration of antidotal
      treatment and shortening the hospital observation period. Currently, there are
      two antidotes used to block ADH-mediated metabolism of EG and methanol: ethanol
      and fomepizole. In this review, the advantages and disadvantages of both
      antidotes in terms of efficacy, safety and costs are discussed in order to help
      the physician to decide which antidote is appropriate in a specific clinical
      setting. 

PMID- 24659590
TI  - Compression therapy in patients with orthostatic hypotension: a systematic
      review.
AB  - AIM: Orthostatic hypotension is common, especially in the elderly, and it is
      strongly associated with discomfort and falls. Physicians may sometimes prescribe
      compression therapy, but the beneficial effect of this treatment in orthostatic
      hypotension is unclear. The aim of this review was to summarise all available
      evidence on the effect of four different levels of compression therapy in the
      treatment of orthostatic hypotension: knee-length, thigh-length, full-length and
      abdominal compression only. METHODS: A systematic search was performed in PubMed,
      Embase and Cochrane databases. RESULTS: A literature search identified 1232
      reports; 11 publications were selected for inclusion in this review. The quality
      of studies was heterogenous and generally poor. Full length compression (lower
      limbs and abdomen) and compression of solely the abdomen were found to be
      superior to knee-length and thigh-length compression. Both significantly reduced
      the fall in systolic blood pressure after postural change. Symptoms of
      orthostatic hypotension experienced by patients were improved the most by full
      length compression. CONCLUSIONS: When other interventions fail to ameliorate
      symptoms, compression therapy can be considered. This review demonstrates that
      compression treatment should include the abdomen as this has the greatest
      beneficial effect. However, this review also displays the paucity of evidence for
      compression therapy for patients with orthostatic hypotension, and further
      investigation is certainly warranted.

PMID- 24659591
TI  - Proton pump inhibitors do not increase the risk of acute rejection.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid
      (MPA). Proton pump inhibitors impair exposure to MPA due to incomplete conversion
      from MMF. Lower exposure to MPA could result in an increased risk of acute
      rejection. We investigated whether MMF-treated renal transplant patients who
      concomitantly used pantoprazole as ulcer prophylaxis had a higher risk of acute
      rejection within the first three months after transplantation than those who used
      ranitidine. METHODS: We performed a retrospective study in adult patients who
      underwent kidney transplantation between January 2007 and December 2011. Their
      immunosuppressive therapy consisted of steroids, tacrolimus and MMF and they used
      either pantoprazole or ranitidine as ulcer prophylaxis. RESULTS: 202 patients
      were included: 125 using pantoprazole and 77 using ranitidine. There was no
      difference in the number of patients with biopsy-proven acute rejection (BPAR):
      13 (10.4%) in the pantoprazole group versus 7 (9.1%) in the ranitidine group
      (NS). Also after correction for inequalities between the two groups, there was no
      significant relationship between the risk of BPAR and the type of anti-ulcer
      agent. CONCLUSION: There was no evidence for an increased incidence of BPAR in
      renal transplant patients who use pantoprazole in combination with MMF.

PMID- 24659592
TI  - Nephrocalcinosis as adult presentation of Bartter syndrome type II.
AB  - Bartter syndrome consists a group of rare autosomal-recessive renal tubulopathies
      characterised by renal salt wasting, hypokalaemic metabolic alkalosis,
      hypercalciuria and hyperreninaemic hyperaldosteronism. It is classified into five
      types. Mutations in the KCNJ1 gene (classified as type II) usually cause the
      neonatal form of Bartter syndrome. We describe an adult patient with a homozygous
      KCNJ1 mutation resulting in a remarkably mild phenotype of neonatal type Bartter
      syndrome.

PMID- 24659593
TI  - Swelling of the eyelids. Kaposi sarcoma.

PMID- 24659594
TI  - A 73-year-old male with jaundice and acute kidney injury. Bile cast nephropathy.

PMID- 24659595
TI  - A tropical flower? Hydatid cysts or hydatid disease.

PMID- 24659596
TI  - A solitary lung mass in a 46-year-old man. Rounded atelectasis.

PMID- 24659597
TI  - Estimated hospital health costs of chronic abdominal pain in the Netherlands.
AB  - aim: Calculation of the hospital costs of chronic abdominal pain in the
      Netherlands. DESIGN: Cross-sectional study. METHODS: We selected 'Diagnosis
      Related Groups' (DRG) of disorders that are associated with chronic abdominal
      pain from a large teaching hospital and a tertiary referral centre. For each DRG
      we determined the percentage of patients that can present with abdominal pain.
      The total costs for both hospitals were calculated using the registered quantity
      of the DRGs. Each DRG was categorised by somatic and functional origin. The
      results were subsequently extrapolated to the entire Dutch population demanding
      hospital care for chronic abdominal pain. Finally, the percentage and associated
      costs were calculated for patients who had two or more separate diagnoses for
      chronic abdominal pain in the field of gastroenterology, gynaecology, internal
      medicine and urology. RESULTS: The yearly outpatient and (day) clinical health
      costs for patients with chronic abdominal pain in the Netherlands were
      approximately ?623 million (gastroenterology ?226 million; gynaecology ?303
      million; internal medicine ?63 million; and urology ?31 million). Of these
      diagnoses, 53.6% were related to functional disorders, which accounts for
      approximately ?220 million per year. The yearly costs of patients who had at
      least two separate diagnoses within one year for chronic abdominal pain were
      estimated at ?23.5 million per year. CONCLUSION: Chronic abdominal pain is a
      common problem that entails significant healthcare costs in the Netherlands of
      which functional diagnoses compromise a significant amount.

PMID- 24659598
TI  - Trends in the outcomes of Dutch haematological patients receiving intensive care
      support.
AB  - BACKGROUND: Because of the assumed dismal prognosis there is still reluctance to
      admit haematological patients to the intensive care unit (ICU). This study was
      conducted to determine trends in outcome of allogeneic haematopoietic stem cell
      transplant (HSCT) recipients transferred to the intensive care unit in a Dutch
      tertiary care hospital. METHODS: All patients who received allogeneic HSCT
      between 2004-2010 were included in the analyses. Baseline and outcome
      characteristics were compared and risk factors for ICU admission and survival
      were identified. Changes in outcome over time of three cohorts of HSCT recipients
      were investigated. RESULTS: Of 319 consecutive HSCT recipients, 49 (15%) were
      transferred to the ICU for a median (IQR) of 10 (6-45) days following their
      transplantation, of whom 43% were severely neutropenic and 90% had received
      systemic immunosuppressive therapy for graft-versus-host disease prophylaxis.
      Univariate logistic regression showed that transplantation from an unrelated
      donor and myeloablative conditioning were significant risk factors for ICU
      admission. Prolonged use of vasopressors, invasive mechanical ventilation and
      male gender were significant predictors for ICU mortality, while neutropenia and
      graft-versus-host disease were not. Over the years, APACHE-II severity of illness
      scores remained unchanged (21.0+/-7.1, 20.1+/-5.6, 21.2+/-6.6), while 100-day
      post-transplant mortality of patients who had been transferred to the ICU
      decreased significantly from 78% (2004/2005) to 57% (2006/2007), and 35%
      (2008/2009). CONCLUSIONS: While for allogeneic HSCT patients the severity of
      illness on admission to the ICU did not change, the 100-day post-transplant
      survival improved. These data indicate that reluctance to submit haematological
      patients to the ICU is not warranted.

PMID- 24659599
TI  - Cerebrovascular events during nilotinib treatment.

PMID- 24659600
TI  - Red blood cell distribution width: an emerging predictor for mortality in
      critically ill patients?

PMID- 24659601
TI  - The blood exposome and its role in discovering causes of disease.
AB  - BACKGROUND: Since 2001, researchers have examined the human genome (G) mainly to
      discover causes of disease, despite evidence that G explains relatively little
      risk. We posit that unexplained disease risks are caused by the exposome (E;
      representing all exposures) and G * E interactions. Thus, etiologic research has
      been hampered by scientists' continuing reliance on low-tech methods to
      characterize E compared with high-tech omics for characterizing G. OBJECTIVES:
      Because exposures are inherently chemical in nature and arise from both
      endogenous and exogenous sources, blood specimens can be used to characterize
      exposomes. To explore the "blood exposome" and its connection to disease, we
      sought human blood concentrations of many chemicals, along with their sources,
      evidence of chronic-disease risks, and numbers of metabolic pathways. METHODS:
      From the literature we obtained human blood concentrations of 1,561 small
      molecules and metals derived from foods, drugs, pollutants, and endogenous
      processes. We mapped chemical similarities after weighting by blood
      concentrations, disease-risk citations, and numbers of human metabolic pathways.
      RESULTS: Blood concentrations spanned 11 orders of magnitude and were
      indistinguishable for endogenous and food chemicals and drugs, whereas those of
      pollutants were 1,000 times lower. Chemical similarities mapped by disease risks
      were equally distributed by source categories, but those mapped by metabolic
      pathways were dominated by endogenous molecules and essential nutrients.
      CONCLUSIONS: For studies of disease etiology, the complexity of human exposures
      motivates characterization of the blood exposome, which includes all biologically
      active chemicals. Because most small molecules in blood are not human
      metabolites, investigations of causal pathways should expand beyond the
      endogenous metabolome.

PMID- 24659602
TI  - The deletion of TonB-dependent receptor genes is part of the genome reduction
      process that occurs during adaptation of Pseudomonas aeruginosa to the cystic
      fibrosis lung.
AB  - Chronic Pseudomonas aeruginosa infections are the main cause of morbidity among
      patients with cystic fibrosis (CF) due to persistent lung inflammation caused by
      interaction between this bacterium and the immune system. Longitudinal studies of
      clonally related isolates of a dominant CF clone have indicated that genome
      reduction frequently occurs during adaptation of P. aeruginosa in the CF lung. In
      this study, we have evaluated the P. aeruginosa population structure of patients
      attending the Universitair Ziekenhuis Brussel (UZ Brussel) CF reference center
      using a combination of genotyping methods. Although the UZ Brussel P. aeruginosa
      CF population is characterized by the absence of a dominant CF clone, some
      potential interpatient transmissions could be detected. Interestingly, one of
      these clones showed deletion of the alternative type I ferripyoverdine receptor
      gene fpvB. Furthermore, we found that several other TonB-dependent receptors are
      deleted as well. The genome of one potentially transmissible CF clone was
      sequenced, revealing large deleted regions including all type III secretion
      system genes and several virulence genes. Remarkably, a large number of deleted
      genes are shared between the P. aeruginosa CF clone described in this study and
      isolates belonging to the dominant Copenhagen CF DK2 clone, suggesting parallel
      evolution.

PMID- 24659603
TI  - Spatial distribution of persistent organic pollutants in the surface water of
      River Brahmaputra and River Ganga in India.
AB  - Persistent organic pollutants (POPs) like organochlorine pesticides (OCPs),
      polychlorinated biphenyles (PCBs) and polyaromatic hydrocarbons (PAHs) are
      discharged in surface water by various point and nonpoint sources thereby
      degrading the functioning of the ecosystem and threatening human health.
      Chlorinated pesticides such as Hexachlorocyclohexane (HCHs) and
      Dichlorodiphenyltrichloroethane (DDTs) are effective pest control chemicals, used
      in agriculture and public health activities (malaria eradication, etc.) in India
      for the past several decades and are still in use. POPs can cause endocrine
      disruption and food chain biomagnification because of their lipophilicity and
      environmental persistence. This study aims to assess the environmental occurrence
      and spatial distribution of OCPs, PAHs and PCBs in the surface water of River
      Brahmaputra and Ganga ending at the of the Bay of Bengal.The order of
      organochlorine pesticides is as: heptachlor>HCHs>DDTs>dieldrin>aldrin>endosulfan.
      Diamond Harbour and Bakkhali were the two places with elevated level of all
      individual HCH isomers compared to all other sites. beta-Endosulfan and alpha
      Endosulfan were high at Dibrugarh than other sampling sites. This is due to the
      ongoing use of Endosulfan in the tea estates in Assam especially the estates
      close to the town of Dibrugarh. p,p'-DDT and o,p'-DDT levels indicate the fresh
      input of DDT in all the sampling sites. Heptachlor has been observed in 57% of
      the total samples reported in the present study.These reasons may attribute to
      high deposition of pesticides in the surface water of Ganga and Brahmaputra.In
      addition the catchments area of the Ganga River is surrounded by agricultural
      lands so a relatively higher residue of pesticides was prevalent. Sigma27 PCBs
      varied from BDL to 142 (Avg+/-SD, 3.96+/-6.71) ng L-1. PCB-18, PCB-52 & PCB-44
      showed the highest concentration levels for all the sampling sites. PCB-126 was
      observed in samples taken from sites close to the city limit of Kolkata and Assam
      which is an indication of higher toxic effect from this highly toxic congener.
      PCB-169 was prevalent in most of the sites. The total concentrations of PAHs
      varied from BDL to 31 (Avg+/-SD, 0.2+/-1.5) ug L-1. PAHs concentrations were very
      low as PAHs are particle bound compounds.

PMID- 24659604
TI  - Projected health impacts of heat events in Washington State associated with
      climate change.
AB  - Climate change is predicted to increase the frequency and duration of extreme
      heat events and associated health outcomes. This study used data from the
      historical heat-health outcome relationship, and a unique prediction model, to
      estimate mortality for 2025 and 2045. For each one degree change in humidex above
      threshold, we find a corresponding 1.83% increase in mortality for all ages, all
      non-traumatic causes of death in King County, Washington. Mortality is projected
      to increase significantly in 2025 and 2045 for the 85 and older age group (2.3
      8.0 and 4.0-22.3 times higher than baseline, respectively).

PMID- 24659605
TI  - Identification of key residues in the formate channel FocA that control import
      and export of formate.
AB  - The formate-nitrite transporter (FNT) family comprises pentameric channels that
      transport monovalent anions. The prototype of this family is the formate channel
      (FocA), which was originally identified as a formate channel in Escherichia coli.
      Each protomer in the channel has a pore with structural features that include
      periplasmic and cytoplasmic constriction sites, which are likely important for bi
      directional gating of substrate passage. Highly conserved amino acid residues
      within FocA previously identified in structural studies are predicted to be
      important in the control of formate translocation. Here we present a first
      detailed in vivo analysis of these residues using a combined targeted amino acid
      exchange and formate-responsive lacZ fusion-based reporter approach. Sixteen
      exchanges were made and each variant was shown to be largely unaffected in its
      secondary and quaternary structure. The invariant H209 and T91 residues, which
      form part of the lower constriction site linking the Omega-loop with the pore
      cavity, proved to be important in governing the directionality of formate passage
      through the pore. A predicted salt-bridge triad of E208-K156-N213 along with the
      cytoplasmically-oriented N-terminal helix are also involved in pH-dependent
      gating of the channel. Together, our data are consistent with passive export and
      import of formate or formic acid through the channel.

PMID- 24659606
TI  - Changing from glucose to HbA1c for diabetes diagnosis: predictive values of one
      test and importance of analytical bias and imprecision.
AB  - BACKGROUND: In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted
      from March 2012. We evaluated the change in the number of diabetes cases
      diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG),
      and estimated the influence of analytical variation and bias on the HbA1c-based
      prevalence of diabetes. METHODS: The study population constituted 4239
      individuals not known to have diabetes randomly selected from all inhabitants
      aged 25-75 years in the former County of Vejle, Denmark. The number of
      undiagnosed patients with diabetes in the study population using FPG or HbA1c as
      the diagnostic criterion was estimated. Furthermore, changes in the analytical
      bias and coefficient of variation (CV) for HbA1c analysis were simulated and the
      effect on the number of diabetes cases was observed. RESULTS: Changing the
      diagnostic test from FPG to HbA1c reduced the number of patients with diabetes by
      approximately 46% based on one measurement. The predictive value of one test of
      HbA1c was 91% versus only 66% for one test of FPG. Analytical variation had a
      much greater impact on the number of patients with diabetes than bias. At a bias
      of 0%, an increase of CVanalytical from 2.7% to 3.7% increased the number of
      diabetes cases by 90%. CONCLUSIONS: In the study population, the percentage of
      undiagnosed patients with diabetes aged 25-75 years was reduced from 3.6% (95% CI
      3.0%-4.2%) based on one FPG measurement (FPG >=7.0 mmol/L) to only 1.9% (95% CI
      1.5%-2.3%) if the diagnosis of diabetes was based on the criterion of HbA1c >=48
      mmol/mol (6.5% DCCT).

PMID- 24659607
TI  - Extreme startle and photomyoclonic response in severe hypocalcaemia.
AB  - We report the case of 62-year-old woman referred to our department because of a
      clinical suspicion of tonic-clonic seizures. Clinical examination revealed an
      exaggerated startle reflex, EEG showed a photomyoclonic response, and blood tests
      indicated severe hypocalcaemia. Additional clinical data, treatment strategies,
      and long-term follow-up visits were reported. The present report discusses the
      difficulties in distinguishing between epileptic and non-epileptic startles, and
      shows, for the first time, exaggerated startle reflex and extreme photomyoclonic
      response due to severe hypocalcaemia.

PMID- 24659608
TI  - Development of therapeutic polymeric nanoparticles for the resolution of
      inflammation.
AB  - Liver X receptors (LXRs) attenuate inflammation by modulating the expression of
      key inflammatory genes, making LXRs and their ligands particularly attractive
      candidates for therapeutic intervention in cardiovascular, metabolic, and/or
      inflammatory diseases. Herein, enhanced proresolving activity of polymeric
      nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (LXR-NPs) is
      demonstrated, developed from a combinatorial library of more than 70 formulations
      with variations in critical physicochemical parameters. In vitro studies on
      peritoneal macrophages confirm that LXR-NPs are significantly more effective than
      the free agonist at downregulating pro-inflammatory mediators (MCP-1 and
      TNFalpha), as well as inducing the expression of LXR target genes (ABCA1 and
      SREBP1c). Through a zymosan-induced acute peritonitis in vivo model, LXR-NPs are
      found to be more efficient than free GW3965 at limiting the recruitment of
      polymononuclear neutrophils (50% vs 17%), suppressing the gene expression and
      secretion of pro-inflammatory factors MCP-1 and TNFalpha in peritoneal
      macrophages, and decreasing the resolution interval up to 4 h. Furthermore, LXR
      NPs suppress the secretion of MCP-1 and TNFalpha by monocytes and macrophages
      more efficiently than the commercial drug dexamethasone. Overall, these findings
      demonstrate that LXR-NPs are capable of promoting resolution of inflammation and
      highlight the prospect of LXR-based nanotherapeutics for inflammatory diseases. 

PMID- 24659609
TI  - Protection of tobacco cells from oxidative copper toxicity by catalytically
      active metal-binding DNA oligomers.
AB  - The impact of copper ions on the oxidative and calcium signal transductions,
      leading to cell death in plant cells, have been documented. Copper induces a
      series of biological and chemical reactions in plant cells including the
      oxidative burst reflecting the production of reactive oxygen species and the
      stimulation of calcium channel opening allowing a transient increase in cytosolic
      calcium concentrations. These early events, completed within a few minutes after
      the contact with copper, are known to trigger the development of cell death. The
      effects of DNA fragments with copper-binding motifs as novel plant cell
      protecting agents were assessed using cell suspension cultures of transgenic
      tobacco (Nicotiana tabacum L., cell line BY-2) expressing the aequorin gene. The
      addition of GC-rich double-stranded DNA fragments, prior to the addition of
      copper ions, effectively blocked both the copper-induced calcium influx and cell
      death. In addition, the DNA-Cu complex examined was shown to possess superoxide
      scavenging catalytic activity, suggesting that DNA-mediated protection of the
      cells from copper toxicity is due to the removal of superoxide. Lastly, a
      possible mechanism of DNA-Cu interaction and future applications of these DNA
      fragments in the protection of plant roots from metal toxicity or in aid of phyto
      remediation processes are discussed. 

PMID- 24659610
TI  - Multiple dietary supplements do not affect metabolic and cardio-vascular health.
AB  - Dietary supplements are widely used for health purposes. However, little is known
      about the metabolic and cardiovascular effects of combinations of popular over
      the-counter supplements, each of which has been shown to have anti-oxidant, anti
      inflammatory and pro-longevity properties in cell culture or animal studies. This
      study was a 6-month randomized, single-blind controlled trial, in which 56 non
      obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a
      dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up.
      The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a
      complex of 800 mg each of green, black, and white tea extract, 250 mg of
      pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of
      lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract,
      and 1.0 g fish oil). Both the SUP and CON groups took a daily
      multivitamin/mineral supplement. The main outcome measures were arterial
      stiffness, endothelial function, biomarkers of inflammation and oxidative stress,
      and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with
      10 dietary supplements did not affect arterial stiffness or endothelial function
      in nonobese individuals. These compounds also did not alter body fat measured by
      DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of
      inflammation and oxidative stress. In summary, supplementation with a combination
      of popular dietary supplements has no cardiovascular or metabolic effects in non
      obese relatively healthy individuals.

PMID- 24659611
TI  - Republished research: Implementation research: what it is and how to do it:
      implementation research is a growing but not well understood field of health
      research that can contribute to more effective public health and clinical
      policies and programmes. This article provides a broad definition of
      implementation research and outlines key principles for how to do it.

PMID- 24659612
TI  - Sexual dimorphism in autonomic changes and in the renin-angiotensin system in the
      hearts of mice subjected to thyroid hormone-induced cardiac hypertrophy.
AB  - Based on the relevance of the renin-angiotensin system and the ongoing
      controversy regarding the role of the sympathetic nervous system in thyroid
      hormone-induced cardiac hypertrophy, the aim of the present study was to
      establish whether the putative difference in the degree of cardiac hypertrophy
      exhibited by males and females might be related to differences in the sympathetic
      vagal balance and/or in the cardiac renin-angiotensin system in mice of different
      genders. Male and female mice (n = 117) were given 0.1 mg kg(-1) of
      triiodothyronine or normal saline each day for 10 days consecutively. At the end
      of that period, study of the heart rate variability, spectral analysis and
      histopathological examination were performed to assess the sympathetic-vagal
      balance and the diameter of cardiomyocytes. The cardiac levels of angiotensin I
      and II were also measured. Treatment with triiodothyronine induced a greater
      degree of cardiac hypertrophy in male (~73%) than in female mice (~42%). This
      difference was attributed to greater modulation of the sympathetic nervous system
      and higher levels of angiotensin I and II in male than in female mice. Our data
      indicate that thyroid hormone-induced cardiac hypertrophy was more intense in
      male mice due to the synergic effect of the sympathetic nervous system and the
      cardiac renin-angiotensin system.

PMID- 24659614
TI  - A simple febrile seizure with focal onset.
AB  - Simple febrile seizures last for less than 10 minutes and resolve spontaneously,
      in the context of a febrile illness, without focal features or recurrence during
      the subsequent 24 hours. We report the case of fortuitous video-EEG recording of
      a FS, clinically classified as "simple", which demonstrated a focal, temporal
      onset. This clinical finding is in agreement with animal model studies
      demonstrating focal onset.

PMID- 24659613
TI  - Neural control of blood flow during exercise in human metabolic syndrome.
AB  - alpha-Adrenergic-mediated vasoconstriction is greater during simulated exercise
      in animal models of metabolic syndrome (MetSyn) when compared with control
      animals. In an attempt to translate such findings to humans, we hypothesized that
      adults with MetSyn (n = 14, 35 +/- 3 years old) would exhibit greater alpha
      adrenergic responsiveness during exercise when compared with age-matched healthy
      control subjects (n = 16, 31 +/- 3 years old). We measured muscle sympathetic
      nerve activity (MSNA; microneurography) and forearm blood flow (Doppler
      ultrasound) during dynamic forearm exercise (15% of maximal voluntary
      contraction). alpha-Adrenergic agonists (phenylephrine and clonidine) and an
      antagonist (phentolamine) were infused intra-arterially to assess alpha
      adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was
      ~35% higher in adults with MetSyn (P < 0.05), but did not change in either group
      with dynamic exercise. Clonidine-mediated vasoconstriction was greater in adults
      with MetSyn (P < 0.01). Group differences in vascular responses to phenylephrine
      and phentolamine were not detected (P > 0.05). Interestingly, exercise-mediated
      vasodilatation was greater in MetSyn (P < 0.05). Adults with MetSyn exhibit
      greater resting MSNA and clonidine-mediated vasoconstriction, yet preserved
      functional sympatholysis and higher exercise blood flow during low-intensity hand
      grip exercise when compared with age-matched healthy control subjects. These
      results suggest that adults with MetSyn exhibit compensatory vascular control
      mechanisms capable of preserving blood flow responses to exercise in the face of
      augmented sympathetic adrenergic activity. 

PMID- 24659619
TI  - A mild wet winter.

PMID- 24659615
TI  - Assessing cellular response to functionalized alpha-helical peptide hydrogels.
AB  - alpha-Helical peptide hydrogels are decorated with a cell-binding peptide motif
      (RGDS), which is shown to promote adhesion, proliferation, and differentiation of
      PC12 cells. Gel structure and integrity are maintained after functionalization.
      This opens possibilities for the bottom-up design and engineering of complex
      functional scaffolds for 2D and 3D cell cultures. 

PMID- 24659620
TI  - We must work together to provide a better solution.

PMID- 24659621
TI  - Translation and validation of the Chinese Cardiff Wound Impact Schedule.
AB  - The objectives of the study were to translate the Cardiff Wound Impact Schedule
      (CWIS), a disease-specific quality-of-life measure, into Chinese, and to evaluate
      its psychometric properties. The CWIS went through the full linguistic
      translation process and was evaluated in patients with current diabetic foot
      ulcers (DFU). Patients were categorized using the Wagner grade. Mean CWIS scores
      were compared between categories to evaluate the scale's ability to differentiate
      ulcer severity (Wagner grade). There were a total of 131 consecutive patients
      included in the study. Except item A22 (I am confident that the wound I have will
      heal), the results of item-domain correlation (r ranged from .391 to .827) and
      small-group analysis (critical ratio, P < .05) were satisfactory. Furthermore,
      the Chinese CWIS also demonstrated good criterion validity when correlated with
      the Short Form-36 (r = .79, P < .01). After deleting item 22, exploratory factor
      analysis of the items confirmed the existence of 3 hypothesized domains, physical
      symptoms and daily living (12 items), social life (7 items), and well-being (6
      items), and totally explained 57.194% of the variance. The internal consistency
      of all scales of the Chinese CWIS was consistently high (Cronbach's alpha ranged
      from .789 to .929). Split-half reliability was 0.748. Sensitivity was
      demonstrated between patients with different etiologies of diabetic foot ulcer
      and those with different ulcer severity (Wagner grade). From the authors' view,
      the lately validated Chinese CWIS has good psychometric performance and may be
      appropriately used to assess the health-related quality of life of Chinese
      patients with DFUs. 

PMID- 24659623
TI  - Clinical characteristics and medical costs in patients with diabetic amputation
      and nondiabetic patients with nonacute amputation in central urban hospitals in
      China.
AB  - The objective was to analyze the clinical characteristics, amputation level,
      final outcome of amputation, and medical cost between diabetic amputation and
      nonacute amputation in China central urban hospitals. For year 2010, amputation
      data from 19 central municipal general hospitals located in different big cities
      in China were retrospectively analyzed according to a standardized protocol. A
      total of 308 amputation patients were recruited. The patients were divided into
      diabetic amputation group (n = 174) and nonacute amputation group (n = 134). A
      total of 27.3% of the amputated patients or 56.5% of the nonacute patients were
      diabetic patients. Compared with nonacute amputation, patients with diabetic
      amputation were older (65.4 +/- 11.6 vs 55.4 +/- 19.6 years, P = .000), with
      higher systolic blood pressure (136.7 +/- 19.7 vs 132.0 +/- 20.3 mm Hg, P =
      .044), higher fasting blood glucose level (8.3 +/- 3.7 vs 5.9 +/- 2.3 mmol/L, P =
      .000), lower triglycerides (TG; 1.3 +/- 0.7 vs 1.6 +/- 1.0 mmol/L, P = .014), and
      lower high-density lipoprotein cholesterol (HDL-C; 1.0 +/- 0.4 vs 1.2 +/- 0.3
      mmol/L, P = .001). Minor amputation was more common in the patients with diabetic
      foot disease than those with nonacute foot disease (55.7% vs 20.1%; chi(2) =
      40.519, P = .000). There were significant differences in days of hospital stay
      (33.5 vs 22.0 days) and medical cost (US$5932 vs US$4101) between the 2 groups.
      The patients with diabetic amputation were older with higher blood glucose,
      higher blood pressure, lower TG level, and lower HDL-C level. Most of them
      required minor amputation. More diabetic patients underwent repeated amputation.
      Their hospital stay was longer with significantly higher medical costs. 

PMID- 24659622
TI  - Effect of daptomycin on local interleukin-6, matrix metalloproteinase-9, and
      metallopeptidase inhibitor 1 in patients with MRSA-infected diabetic foot.
AB  - Infection is a major cause of the diabetic foot syndrome that is promoted by the
      increased burden of multiresistant germs like methicillin-resistant
      Staphylococcus aureus (MRSA). Maximizing positive outcome for serious MRSA
      infections requires an aggressive treatment approach and careful monitoring of
      the healing process. Therefore, we examined 8 patients with MRSA-infected
      diabetic foot syndrome of Wagner classification grade 2 or 3 (corresponding to
      the Texas classification stage 2 or 3) during antibiotic treatment with
      daptomycin. We documented the wound size and obtained samples of wound secretion
      for analyses of proinflammatory interleukin-6 (IL-6), protease (matrix
      metalloproteinase-9 [MMP-9]), and antiprotease (metallopeptidase inhibitor 1
      [TIMP-1]) activity. During the course of anti-MRSA therapy, we observed a
      decrease in the concentration of local IL-6 within the first 3 days followed by a
      decrease of MMP-9 and an increase of TIMP-1. Finally, a reduction of wound size
      was documented. The present data show that efficient antimicrobial treatment with
      daptomycin has a number of beneficial effects on wound healing at the molecular
      level in MRSA-infected diabetic foot ulcers. 

PMID- 24659624
TI  - Reducing major lower extremity amputations after the introduction of a
      multidisciplinary team for the diabetic foot.
AB  - We analyzed the incidence of lower extremity amputations (LEAs) in the 3rd Health
      Care Area of Madrid before and after the March 2008 introduction of a
      multidisciplinary team for managing diabetic foot disease. We compared the
      amputation rates in people with and without diabetes during 2 periods: before
      (2001-2007) and after (2008-2011) the introduction of a Multidisciplinary
      Diabetic Foot Unit (MDFU). We also analyzed the trend of the amputation rates by
      joinpoint regression analysis and measured the annual percentage change (APC).
      During the study period, 514 nontraumatic LEAs were performed, 374 (73%) in
      people with diabetes and 140 (27%) in people without the disease. The incidence
      of LEAs showed a significant reduction in major amputations in people with
      diabetes, from 6.1 per 100 000 per year (95% confidence interval [CI] = 4.9 to
      7.2), in the 2001 to 2007 period, to 4.0 per 100 000 per year (95% CI = 2.6 to
      5.5) in the 2008 to 2011 period (P = .020). There were no changes in incidence of
      minor or total amputations in the diabetic population or in amputations in the
      nondiabetic population during the study period. Joinpoint regression analysis
      showed a significant reduction in the incidence of major LEAs in diabetic
      population with an APC of -6.6% (95% CI = -10.2 to -2.8; P = .003), but there
      were no other significant changes. This study demonstrates that the introduction
      of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist,
      for managing diabetic foot disease is associated with a reduction in the
      incidence of major amputations in patients with diabetes. 

PMID- 24659625
TI  - Pharmacological evaluation and chemical standardization of an ayurvedic
      formulation for wound healing activity.
AB  - Wound healing is a topic of substantial prominence in Ayurveda, the Indian
      traditional system of medicine. Test drug Kshatantak Malam (KM), otherwise named
      as Baharer Nani, is described in Ayurveda since a long time for wound healing
      activity but necessitates scientific base. The test drug was prepared in the form
      of natural ointment with the plants like Achyranthes aspera, Allium cepa, and
      Canabis sativa under the base of butter in a specialized form of preparation.
      Chemical standardization was made on the basis of the physical character,
      rancidity test, extractive value, thin-layer chromatography, and gas
      chromatography. An 8-mm-diameter full-thickness punch was produced in Wistar
      rats. The test drug was applied topically and compared with standard comparators
      like framycetin ointment and povidone iodine ointment. Effects were observed on
      the basis of physical parameters like wound contraction size (mm(2)), wound
      index, healing period (days), tensile strength (g) and biochemical parameters
      like tissue DNA (mg/g), RNA (mg/g), total protein (mg/g), hydroxyproline (mg/g),
      PAGE study, and histopathological observations. Significant results (P < .05)
      were observed with KM in the punch wound model on the basis of various physical,
      biochemical, and histopathological parameters. The drug was found to be safe in
      acute and chronic toxicity models in animals. Chemically it is enriched with
      fatty substances. 

PMID- 24659626
TI  - Promising role of ANGPTL4 gene in diabetic wound healing.
AB  - Diabetes mellitus (DM) is one of the severe metabolic disorders of carbohydrate
      metabolism worldwide. Developing countries are at higher risk of DM, and there is
      significant evidence that it is epidemic in many economically developing and
      newly industrialized countries. Among all other complications associated with DM,
      delayed wound healing is a major concern in diabetic patients. Wound healing is a
      natural healing process that starts immediately after injury. This involves
      interaction of a complex cascade of cellular events that generates resurfacing,
      reconstitution, and restoration of the tensile strength of injured skin. There
      are multiple factors responsible for delayed wound healing among which the
      contribution of DM has been well documented. The wound healing process is also
      delayed by the metabolic, vascular, neurological, and inflammatory alterations,
      which are well known in both type 1 and type 2 diabetes. Keratinocytes are
      crucial for wound re-epithelialization, and defects in directed migration of
      keratinocytes due to DM are associated with the delayed wound healing process.
      Many factors responsible for re-epithelialization have been identified,
      characterized, and well described; however, the genes responsible for the healing
      process have only partially been illustrated. This article will therefore focus
      on the efficacy of ANGPTL4 (angiopoietin-like 4) gene, which plays a novel role
      in keratinocyte migration during wound healing. 

PMID- 24659627
TI  - Confirming an expanded spectrum of SCN2A mutations: a case series.
AB  - Mutations in sodium channel genes are highly associated with epilepsy. Mutation
      of SCN1A, the gene encoding the voltage gated sodium channel (VGSC) alpha subunit
      type 1 (Nav1.1), causes Dravet syndrome spectrum disorders. Mutations in SCN2A
      have been identified in patients with benign familial neonatal-infantile epilepsy
      (BFNIE), generalised epilepsy with febrile seizures plus (GEFS+), and a small
      number of reported cases of other infantile-onset severe intractable epilepsy.
      Here, we report three patients with infantile-onset severe intractable epilepsy
      found to have de novo mutations in SCN2A. While a causal role for these mutations
      cannot be directly established, these findings contribute to growing evidence
      that mutation of SCN2A is associated with a range of epilepsy phenotypes
      including severe infantile-onset epilepsy. 

PMID- 24659629
TI  - Ezogabine treatment of childhood absence epilepsy.
AB  - Generalised-onset absence seizures can be resistant to treatment with currently
      available antiepileptic drugs. Ezogabine (retigabine), a potassium channel
      opener, is approved for the treatment of focal-onset seizures. This is a case
      report of an adult with childhood absence epilepsy whose daily absence seizures
      ceased with adjunctive ezogabine. A 59-year-old woman, with a history of typical
      absence seizures since the age of 6 years, had multiple seizures daily despite
      trials of over 11 antiepileptic drugs. While taking lamotrigine and zonisamide,
      ezogabine at 50 mg daily was added. The dose was slowly increased and once a
      total dose of only 200 mg/day was reached, she became seizure-free for three
      months. After subsequently discontinuing zonisamide, absence seizures returned.
      Further increasing the ezogabine to 400 mg/day, in addition to lamotrigine, did
      not restore seizure freedom, but adding back zonisamide at half dose again
      reduced their frequency. Ezogabine at low dose, added to lamotrigine and
      zonisamide, led to sustained absence seizure freedom. The return of seizures
      after zonisamide discontinuation suggests that the seizure freedom may have been
      the result of the different mechanisms of action of the antiepileptic drugs. 

PMID- 24659628
TI  - MicroRNA-29 induces cellular senescence in aging muscle through multiple
      signaling pathways.
AB  - The mechanisms underlying the development of aging-induced muscle atrophy are
      unclear. By microRNA array and individual qPCR analyses, we found significant up
      regulation of miR-29 in muscles of aged rodents vs. results in young. With aging,
      p85alpha, IGF-1 and B-myb muscle levels were lower while the expression of
      certain cell arrest proteins (p53, p16 and pRB) increased. When miR-29 was
      expressed in muscle progenitor cells (MPC), their proliferation was impaired
      while SA-betagal expression increased signifying the development of senescence.
      Impaired MPC proliferation resulted from interactions between miR-29 and the 3'
      UTR of p85a, IGF-1 and B-myb, suppressing the translation of these mediators of
      myoblast proliferation. In vivo, electroporation of miR-29 into muscles of young
      mice suppressed the proliferation and increased levels of cellular arrest
      proteins, recapitulating aging-induced responses in muscle. A potential stimulus
      of miR-29 expression is Wnt-3a since we found that exogenous Wnt-3a stimulated
      miR-29 expression 2.7-fold in primary cultures of MPCs. Thus, aging-induced
      muscle senescence results from activation of miR-29 by Wnt-3a leading to
      suppressed expression of several signaling proteins (p85alpha, IGF-1 and B-myb)
      that act coordinately to impair the proliferation of MPCs contributing to muscle
      atrophy. The increase in miR-29 provides a potential mechanism for aging-induced
      sarcopenia. 

PMID- 24659630
TI  - Engineered repressors are potent inhibitors of androgen receptor activity.
AB  - Prostate cancer growth is dependent upon the Androgen Receptor (AR) pathway,
      hence therapies for this disease often target this signalling axis. Such
      therapies are successful in the majority of patients but invariably fail after a
      median of 2 years and tumours progress to a castrate resistant stage (CRPC). Much
      evidence exists to suggest that the AR remains key to CRPC growth and hence
      remains a valid therapeutic target. Here we describe a novel method to inhibit AR
      activity, consisting of an interaction motif, that binds to the AR ligand-binding
      domain, fused to repression domains. These 'engineered repressors' are potent
      inhibitors of AR activity and prostate cancer cell growth and importantly inhibit
      the AR under circumstances in which conventional therapies would be predicted to
      fail, such as AR mutation and altered cofactor levels. 

PMID- 24659631
TI  - Ibrutinib inhibits BCR and NF-kappaB signaling and reduces tumor proliferation in
      tissue-resident cells of patients with CLL.
AB  - Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental factors for
      proliferation and survival. In particular, tissue-resident CLL cells show
      prominent activation of both B-cell receptor (BCR) and NF-kappaB pathways. We
      evaluated the in vivo effects of ibrutinib, a Bruton tyrosine kinase (BTK)
      inhibitor on tumor cell activation and proliferation in the blood, lymph node,
      and bone marrow of patients with CLL. Applying validated pathway-specific gene
      signatures, we detected a rapid and sustained downregulation of BCR and NF-kappaB
      signaling in CLL cells from both the peripheral blood and tissue compartments
      during ibrutinib treatment. Ibrutinib reduced phosphorylation of PLCgamma2 and
      ERK and decreased nuclear protein expression of NF-kappaB p50. Ibrutinib
      significantly decreased tumor proliferation and expression of surface activation
      markers CD69 and CD86, independent of prognostic factors such as IGHV mutational
      status, chromosome 17p deletion, or prior treatment history. Interestingly,
      stronger inhibition of BCR signaling in lymph node resident CLL cells after one
      dose of ibrutinib was associated with a higher rate of nodal response at the end
      of cycle 2. Together, these data validate on-target effects of BTK inhibition in
      the tissue compartments and demonstrate that ibrutinib effectively inhibits
      pathways that promote tumor cell activation and proliferation in vivo. This study
      is registered at www.clinicaltrials.gov as #NCT01500733. 

PMID- 24659633
TI  - MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic
      islands.
AB  - Definitive erythropoiesis takes place at erythroblastic islands, where
      erythroblasts proliferate and differentiate in association with central
      macrophages. At the final stage of erythropoiesis, pyrenocytes (nuclei surrounded
      by plasma membranes) are excluded from erythroblasts, expose phosphatidylserine
      (PtdSer), and are engulfed by the macrophages in a PtdSer-dependent manner.
      However, the molecular mechanism(s) involved in the engulfment of pyrenocytes are
      incompletely understood. Here, we constructed an in vitro assay system for the
      enucleation and engulfment of pyrenocytes using a methylcellulose-based culture.
      As reported previously, erythroblasts were bound to macrophages via interactions
      between integrin-alpha4beta1 on erythroblasts and Vcam1 on macrophages. After
      enucleation, the resulting pyrenocytes exhibited a reduced affinity for Vcam1
      that correlated with the presence of inactive integrin-alpha4beta1 complexes. The
      pyrenocytes were then engulfed by the macrophages via a MerTK-protein S-dependent
      mechanism. Protein S appeared to function as a bridge between the pyrenocytes and
      macrophages by binding to PtdSer on the pyrenocytes and MerTK on the macrophages.
      Normally, NIH3T3 cells do not engulf pyrenocytes, but when they were transformed
      with MerTK, they efficiently engulfed pyrenocytes in the presence of protein S.
      These results suggest that macrophages use similar mechanisms to engulf both
      pyrenocytes and apoptotic cells. 

PMID- 24659632
TI  - The glutaminase activity of L-asparaginase is not required for anticancer
      activity against ASNS-negative cells.
AB  - L-Asparaginase (L-ASP) is a key component of therapy for acute lymphoblastic
      leukemia. Its mechanism of action, however, is still poorly understood, in part
      because of its dual asparaginase and glutaminase activities. Here, we show that L
      ASP's glutaminase activity is not always required for the enzyme's anticancer
      effect. We first used molecular dynamics simulations of the clinically standard
      Escherichia coli L-ASP to predict what mutated forms could be engineered to
      retain activity against asparagine but not glutamine. Dynamic mapping of enzyme
      substrate contacts identified Q59 as a promising mutagenesis target for that
      purpose. Saturation mutagenesis followed by enzymatic screening identified Q59L
      as a variant that retains asparaginase activity but shows undetectable
      glutaminase activity. Unlike wild-type L-ASP, Q59L is inactive against cancer
      cells that express measurable asparagine synthetase (ASNS). Q59L is potently
      active, however, against ASNS-negative cells. Those observations indicate that
      the glutaminase activity of L-ASP is necessary for anticancer activity against
      ASNS-positive cell types but not ASNS-negative cell types. Because the clinical
      toxicity of L-ASP is thought to stem from its glutaminase activity, these
      findings suggest the hypothesis that glutaminase-negative variants of L-ASP would
      provide larger therapeutic indices than wild-type L-ASP for ASNS-negative
      cancers.

PMID- 24659635
TI  - Cobalamin deficiency triggering de novo status epilepticus.
AB  - Cobalamin deficiency is included in the spectrum of very uncommon underlying
      causes of status epilepticus (SE) and the literature contains very few such
      cases. We herein report a case of unusual presentation of cobalamin (vitamin B12)
      deficiency with de novo SE with the intention to bolster the argument that a de
      novo manifestation of SE due to cobalamin deficiency might not be that uncommon.
      We also support the importance of prompt identification and treatment of the
      underlying causes of SE, particularly those which are uncommon. 

PMID- 24659636
TI  - The role of depression and neuroimmune axis in the prognosis of cancer patients.
AB  - New exciting research in psycho-oncology has shed light on the mechanisms by
      which biobehavioral signaling in cancer interplays with the neuroimmune axis, as
      well as on the progression and mortality of cancer patients. Cancer and cancer
      therapy can collectively result in inflammation and cytokine production, which
      have been associated with occurrence of depression. Conversely, depression
      supports a chronic activated hypothalamopituitary-adrenal axis (HPA) and further
      determines cortisol and adrenal disturbances, as well as immune dysfunction and
      increased cytokine production. Through these processes, depression is associated
      with a worse cancer outcome. New treatment strategies which counter the aberrant
      pathways between depression and cancer, such as drugs that target cytokines, pro
      inflammatory signaling, neuroendocrine, metabolic pathways and sympathetic
      activation, might disrupt important vehicles for cancer progression. In this
      review, we emphasize the major pathways that link inflammation, depression and
      immunity, in order to highlight potential therapeutic strategies which may become
      of paramount importance to those depressed individuals with cancer that have a
      higher risk for developing a more aggressive disease. 

PMID- 24659638
TI  - Pathogenesis and regulation of cellular proliferation in acute lymphoblastic
      leukemia - the role of Ikaros.
AB  - Acute lymphoblastic leukemia (ALL) is the most common type of leukemia of
      childhood. Over the last 50 years there have been tremendous scientific advances
      in understanding the pathogenesis and the mechanisms that control cellular
      proliferation in ALL. These discoveries led to the development of efficient
      therapeutic regimens that greatly improved survival of children with ALL.
      Recently, several genes have been demonstrated to play a key role in tumor
      suppression and that their deregulation leads to malignant transformation and can
      affect overall survival. This review summarizes the role of Ikaros (IKZF1) in
      tumor suppression and regulation of gene expression in leukemia. Deletions and/or
      mutations of Ikaros have been detected in a large percentage of pediatric and
      adult ALL and reduced Ikaros function has been associated with poor outcome in
      ALL. Ikaros function in chromatin remodeling and epigenetic regulation of gene
      transcription emphasizes the important role of this protein in controlling
      cellular proliferation. In this review, we particularly focus on the role of
      signaling pathways in the regulation of Ikaros activity and its transcriptional
      control in leukemia. 

PMID- 24659637
TI  - Angiogenesis in cancer - general pathways and their therapeutic implications.
AB  - A vast amount of data shows that angiogenesis has a pivotal role in tumor growth,
      progression, invasiveness and metastasis. This is a complex process involving
      essential signaling pathways such as vascular endothelial growth factor (VEGF)
      and Notch in vasculature, as well as additional players such as bone marrow
      derived endothelial progenitor cells. Primary tumor cells, stromal cells and
      cancer stem cells strongly influence vessel growth in tumors. Better
      understanding of the role of the different pathways and the crosstalk between
      different cells during tumor angiogenesis are crucial factors for developing more
      effective anticancer therapies. Targeting angiogenic factors from the VEGF family
      has become an effective strategy to inhibit tumor growth and so far the most
      successful results are seen in metastatic colorectal cancer (CRC), renal cell
      carcinoma (RCC) and non-small cell lung cancer (NSCLL). Despite the initial
      enthusiasm, the angiogenesis inhibitors showed only moderate survival benefit as
      monotherapy, along with a high cost and many side effects. Obviously, other
      important pathways may affect the angiogenic switch, among them Notch signaling
      pathway attracted a large interest because its ubiquitous role in carcinogenesis
      and angiogenesis. Herein we present the basics for VEGF and Notch signaling
      pathways and current advances of targeting them in antiangiogenic, antitumor
      therapy. 

PMID- 24659639
TI  - Management of diaphragmatic peritoneal carcinomatosis: surgical anatomy
      guidelines and results.
AB  - Surgical resections, such as peritoneal stripping (peritonectomy) or full
      thickness resection of the diaphragm (FTDR), are performed for disseminated
      diaphragmatic lesions in patients with peritoneal carcinomatosis (PC). This
      article presents the anatomical steps of diaphragmatic surgery in order to avoid
      intraoperative and postoperative complications and to decrease the morbidity and
      mortality of cytoreductive surgery in patients with PC. 

PMID- 24659640
TI  - Dermatofibrosarcoma protuberans: a rare entity and review of the literature.
AB  - Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant mesenchymal
      tumor. The incidence of DFSP is 0.1% of all cancers and less than 2% of all soft
      tissue sarcomas (STS). It can appear at any age, most commonly in individuals
      aged between 20 and 50 years. The usual location of DFSP is the trunk and it is
      limited to the dermis. Wide radical excision is the preferred surgical method for
      therapy of DFSP without distant metastasis. The probability of regional or
      distant metastases is less than 5%. Patients with positive or close surgical
      margins have an elevated risk of local recurrence after resection. Adjuvant
      radiotherapy administered either before or after the surgical treatment reduces
      the risk of local recurrence. 

PMID- 24659641
TI  - A novel targeted therapy in breast cancer: cyclin dependent kinase inhibitors.
AB  - Breast cancer is the most common cancer in women worldwide. Understanding the
      biology of this tumor is a prerequisite for selecting an appropriate treatment.
      Cell cycle alterations are seen in many cancers such as breast cancer. Newly
      popular targeted agent in breast cancer are cyclin dependent kinase inhibitors
      (CDKIs) which are agents inhibiting the function of cyclin dependent kinases
      (CDKs). They are categorized as selective and non-selective inhibitors of CDK.
      CDKIs have been tried as monotherapy and combination therapy. Palbocyclib is now
      a promising CDKI used in breast cancer. Nowadays palbocyclib is designed for a
      phase III trial for estrogen receptor (ER) positive breast cancer after showing
      favorable results in progression free survival in a phase II trial. 

PMID- 24659642
TI  - Quality assurance in Health Services: the paradigm of radiotherapy.
AB  - INTRODUCTION: In radiotherapy, a team of highly specialised professionals co
      operate in planning and delivery of treatment and are responsible for the
      effectiveness and safety of the service. The aim of this article was to present
      the necessity and features of a quality assurance (QA) program in radiotherapy
      through literature review. METHODS: A search was carried out in Scirus, Medline/
      PubMed databases using the keywords "clinical oncology", "radiation oncology",
      "radiotherapy", "oncology practice", "quality assurance" and "quality of care".
      Twenty-nine articles were chosen covering the period 1995-2007. Further
      information was obtained from the Royal College of Radiologists' UK website.
      RESULTS: QA was relevant to three aspects of radiotherapy: 1) clinical, involving
      resources (staffing and equipment), procedures (treatment planning, follow up)
      and results (tumor control, toxicity); 2) medical physics, involving the
      measurements necessary for the safety and precision of equipment; and 3)
      technical, involving the accurate plan implementation and the smooth function of
      treatment machines. International guidelines defined best practice in diagnosis
      and treatment of cancer patients. Moreover, the principles of quality management
      provided the tools not only for a reasonable use of limited resources but also
      for continuous improvement of organisations towards patient- centred services.
      CONCLUSION: Quality in radiotherapy is a dynamic concept that needs to be
      measured and re-evaluated using scientific methods and feedback by the users.
      Successful implementation of a QA program in radiotherapy requires expertise,
      training and co-ordination in an environment of teamwork.

PMID- 24659643
TI  - Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside
      view of their role and clinical significance.
AB  - Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a
      family of 15 homologous serine proteases, participating in numerous processes of
      normal physiology. Considering the irreversible impact of proteases on
      substrates, the tissue-dependent regulation of KLKs activity becomes crucial for
      their beneficial role in normal homeostasis. Moreover, KLKs expression is
      strongly regulated at the transcriptional and post-transcriptional level by
      steroid hormones and miRNAs, respectively. Deregulation of KLKs expression,
      secretion and/or activation has been observed in most human malignancies and
      there is a trend to identify their role in the multi-complex process of cancer
      development. The identification of extracellular matrix (ECM) proteins, cell
      surface receptors, cell-surface adhesion molecules and growth factors among
      substrates, clearly support the driving role of KLK abnormal expression and
      function during tumorigenesis and cancer progression. KLKs have also clinical
      utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer.
      In this review, we tried to summarize the existing literature about the role of
      KLKs in gastrointestinal cancers as well as to emphasize their clinical
      significance for patients' prognosis. 

PMID- 24659644
TI  - The challenge of pulmonary endobronchial chondromatous hamartomas.
AB  - Pulmonary chondromatous (or chondroid) hamartomas are common benign tumours of
      the lung and may be either parenchymal or endobronchial. The latter are only
      rarely encountered and have a variation in their clinical presentation related to
      the endobronchial obstructive lesion, including atelectasis, pneumonia,
      hemoptysis. If not diagnosed early and treated properly, endobronchial hamartomas
      can cause irreversible lung damage. We present a review of the recent English
      literature over the diagnostic approach and management of pulmonary endobronchial
      chondromatous hamartomas. 

PMID- 24659645
TI  - Survival prognostic factors in patients with colorectal peritoneal carcinomatosis
      treated with cytoreductive surgery and intraoperative hyperthermic
      intraperitoneal chemotherapy: a single institution experience.
AB  - PURPOSE: The aim of this research was to examine overall (OS) and disease-free
      survival (DFS) in patients with colorectal peritoneal carcinomatosis (CRC-PC),
      treated with cytoreductive surgery (CRS) and intraoperative hyperthermic
      intraperitoneal chemotherapy (HIPEC), as well as to analyse factors of prognostic
      significance. METHODS: We included 61 patients with pathological/and computerized
      tomography (CT) confirmation of CRC-PC, treated with CRS+HIPEC from 2005 to 2012.
      Peritoneal Cancer Index (PCI) score was used for quantitative assessment of the
      CRC-PC extent. We performed CRS following the Sugarbaker's principles in all
      patients with PCI <=20 and only in 3/61 (4.92%) patients with PCI >20. HIPEC
      (oxaliplatin 410 mg/m(2) in 2000mL isotonic solution and 41?C) was performed
      using RanD Performer(r) HT perfusion system during 30-60 min. Cox proportional
      hazard regression was used to determine significant factors for OS and DFS.
      RESULTS: The follow-up ranged from 1 to 83 months (median 22). Median OS was 51
      months (95% confidence interval/ CI 22+). Median DFS for patients without
      residual disease (57/61, 93.44%) was 23 months (95% CI 16+). One-, 2- and 6-year
      OS (DFS) were 78.6% (68.3%), 58.7% (46.7%) and 50.5% (38.1%), respectively. By
      the end of the study, 55.74% of the patients were still alive. Cox multivariate
      analysis indicated PCI score as a parameter of highly prognostic significance for
      patients treated with CRS+HIPEC (p<0.001). Patients with PCI (13 (vs PCI >=13)
      had significantly longer OS and DFS (p<0.001), also confirmed for PCI
      subcategories (PCI <7 vs 7<= PCI <13 vs PCI >=13). All patients with PCI <7 are
      still alive. CONCLUSION: Our study indicates that CRS+HIPEC significantly
      improves the survival of CRC-PC patients. This treatment modality should be
      considered as the most suitable in well-selected patients with this disease.

PMID- 24659646
TI  - Capecitabine-related increased mean corpuscular volume of red blood cell may be a
      predictive marker of treatment response and survival in patients with metastatic
      colorectal cancer.
AB  - PURPOSE: Erythrocyte mean corpuscular volume (MCV) increase has been described in
      patients treated with capecitabine. In this study, we sought to evaluate the
      potential association of the erythrocyte MCV increase with tumor response and
      survival in patients with metastatic colorectal cancer (mCRC) treated with
      capecitabine. METHODS: A retrospective review of 131 patients with mCRC who were
      treated with capecitabine for at least 3 months at the Izmir Training and
      Research Hospital was undertaken. Complete blood count (CBC) including red blood
      cell indices were recorded at baseline and after 9 weeks from capecitabine
      treatment. RESULTS: The mean patient age was 57.9 years (range 28- 82). In
      patients treated with capecitabine, MCV increased significantly at 9 weeks
      compared with baseline (p=0.000). Median DeltaMCV [(post-treatment MCV values) -
      (baseline MCV values)] level was 9.3 fL. Patients were grouped according to
      DeltaMCV into two groups (> 9.3 or >= 9.3) in order to carry out survival
      analysis and correlation with tumor response. DeltaMCV was >9.3 in 65 patients
      and <=9.3 in 66 patients. Fifty-six of the 65 patients with DeltaMCV levels >9.3
      and 37 of the 66 patients with DeltaMCV levels <=9.3 had a clinical benefit
      (complete response + partial response + stable disease) from capecitabine
      treatment (p=0.000). The difference between progression-free survival (PFS) and
      overall survival (OS) of the patients who had DeltaMCV>9.3 and those who had
      <=9.3 was statistically significant (9.48 and 6.94 months, p=0.001 respectively;
      and 17.5 and 13.6 months respectively, p=0.018). Univariate analysis suggested
      that a favorable prognosis for OS and PFS was associated with MCV increase
      (p=0.000). In multivariate analysis, MCV increase was independently associated
      with favorable survival outcomes. CONCLUSIONS: Erythrocyte MCV increase may be
      used as a predictive marker for treatment response, PFS and OS in patients with
      mCRC treated with capecitabine.

PMID- 24659647
TI  - Clinical benefit of cetuximab and prognostic value of cetuximab-related skin
      toxicity in metastatic colorectal cancer: a single institution analysis.
AB  - PURPOSE: To evaluate the clinical benefits of cetuximab (CTX) and the prognostic
      value of CTX-related skin toxicity in metastatic colorectal cancer (mCRC)
      patients. METHODS: Sixty patients were tested for KRAS mutation at the Department
      of Oncology, Clinical Centre Nis. We assessed 34 wild-type KRAS mCRC patients
      treated with CTX. All of them were refractory to prior fluoropyrimidine,
      oxaliplatin and irinotecan-based regimens. The maximum grade skin toxicity
      according to treatment cycle was analyzed. Skin toxicity was grouped into
      clinically non-relevant skin toxicity (grade 0-1: Group 1) and clinically
      relevant skin toxicity (grade 2-4: Group 2). RESULTS: Ten out of 33 patients
      (30.30%) achieved partial response (PR). Eight additional patients (24.24%)
      showed stable disease (SD), whereas 15 (45.45%) had disease progression (PD). No
      patient achieved complete response (CR). Overall response rate (ORR) was 30.30%,
      whereas the disease control rate (DCR) was 54.54%.The median progression free
      survival (PFS) was 14 weeks. Some degree of skin toxicity was observed in 79.41%
      (27/34) of the patients. Clinically non-relevant skin toxicity was observed in
      50% (17/34), and clinically relevant in 50 % (17/34) of the patients. Grade 4
      skin toxicity was documented in 1 patient. The mean PFS in Group 1 was 12.65+/
      5.59 weeks and in Group 2 22.82+/-12.16 (p<0.05). The results showed that grade 2
      4 skin toxicity was associated with significantly better response to treatment
      than skin toxicity grade 0-1, with regard to ORR (80.00 vs 20.00%; p<0.05) and
      DCR ( 66.66 vs 33.33%; p<0.05). CONCLUSION: Cetuximab has clinical benefit when
      given alone or in combination with irinotecan in patients with irinotecan
      refractory CRC. Skin toxicity was one of the predictors of response and it was in
      line with what was expected.

PMID- 24659648
TI  - Impact of HPV detection in colorectal adenocarcinoma: HPV protein and chromogenic
      in situ hybridization analysis based on tissue microarrays.
AB  - PURPOSE: Human papillomaviruses (HPV)-mediated cervical carcinogenesis represents
      a well analyzed model of viral implication in epithelial malignant
      transformation. Concerning colorectal cancer, HPV infection seems to be a
      significant genetic event in squamous colon epithelia carcinogenesis, but with an
      unclear role in colon adenocarcinomas (CACs). In the current study, we analyzed
      60 CACs based on tissue microarray (TMA) blocks. METHODS: Cancerous tissues were
      cored, embedded on a tissue microarray block and analyzed by immunohistochemistry
      (HPV IHC) and also by chromogenic in situ hybridization (HPV 16/18 DNA CISH) in
      repetitive serial sections for protein and DNA specific typing detection,
      respectively. RESULTS: Based on HPV IHC and CISH simultaneous analysis, 16
      (26.6%) cases expressed HPV protein. In 7 (11.6%) cores HPV 16/18 DNA signals
      were detected. Overall HPV protein expression and stage of the examined cases
      were significantly correlated with HPV CISH results (p=0.0001, p=0.022,
      respectively). CONCLUSION: A subset of CACs demonstrated HPV infection associated
      with stage. In particular, detection of 16/18 HPV DNA types seemed to be a
      molecular parameter in analyzing genetically CACs, in contrast to HPV protein
      expression which did not offer significant and specific molecular information.

PMID- 24659649
TI  - What is the optimal treatment in clinical stage T3N0M0 rectal cancer?
AB  - PURPOSE: Some previous studies suggested that certain rectal cancer patients with
      stage T3N0 and favorable features may be adequately treated with surgery and
      adjuvant chemotherapy. However, the optimal management of clinical (c) T3N0
      rectal adenocarcinoma based on preoperative imaging is unclear. In this study, we
      aimed to determine the frequency of lymph node metastases in patients clinically
      staged as T3N0 rectal adenocarcinoma following preoperative chemoradiotherapy
      (CTR). METHODS: The medical records of 105 patients with clinico- imaging stage
      T3N0M0 rectal cancer who received preoperative CRT between 2004-2011 were
      retrospectively analyzed. Chemotherapy used concurrently with preoperative
      radiotherapy (RT) was protracted 5-fluorouracil (5FU) infusion. RESULTS: Twenty
      seven percent of the patients clinically staged as T3N0 before preoperative CRT
      had pathological (p) lymph node involvement on surgical material. The rate of
      pathological lymph node involvement was 0% in pT1, 20% in pT2 , 35% in pT3 and
      34% in pT4 patients. A significant association was demonstrated between pT stages
      and pN status (p=0.03). CONCLUSION: Our study demonstrated that the accuracy of
      preoperative imaging for staging rectal cancer is limited because at least 27% of
      the patients may have undetected lymph node involvement after preoperative CRT in
      surgical material.

PMID- 24659650
TI  - Malignancies of the anal canal: a multi-center retrospective analysis in South
      China population.
AB  - PURPOSE: Malignancies of the anal canal are rare diseases associated with limited
      reports and insufficient data. The purpose of this study was to evaluate the
      spectrum of pathological subtypes, therapeutic modalities and prognosis of
      patients in the Chinese population with anal canal malignancies. METHODS: A
      retrospective consecutive series of patients with malignancies of the anal canal
      at 4 institutions in China between January 1990 and December 2011 was studied.
      The patient demographic data, including age, gender, tumor stage, initial
      symptoms, pathological diagnosis, treatment and survival, were collected and
      analyzed from the hospitals' databases. RESULTS: A total of 180 patients (90
      males, 90 females) with anal canal malignancies was identified. Their median age
      was 58 years (range 17-88). The 3 most common pathological subtypes were
      adenocarcinoma (N-129, 71.7%), squamous cell carcinoma (SCC; N=21, 11.7%) and
      melanoma (N7equals;15, 8.3%). Ninety-five adenocarcinoma patients and 10 SCC
      patients were managed with abdominoperineal resection (APR). With a median follow
      up time of 28.9 months (range 1-173), the 5-year overall survival (OS) rates for
      all patients, adenocarcinoma patients, SCC patients and melanoma patients were
      41.9, 40.6, 44.5 and 14.8% respectively, and the median OS time were 46.8, 50.1,
      52.5 and 25.0 months, respectively (p=0.173). CONCLUSION: Adenocarcinoma was the
      major histological subtype in Chinese patients with anal canal malignancies. APR
      based combined modality treatment was the first choice for the past two decades,
      whereas multidisciplinary treatment was not performed adequately. The management
      of SCC must be standardized in South China population. In the future, randomized
      clinical trials are warranted for the optimal treatment options of anal canal
      adenocarcinoma patients.

PMID- 24659651
TI  - HER2/CHR 17 tissue microarray chromogenic in situ hybridization analysis in colon
      adenocarcinoma: multiple gene signals vs protein expression.
AB  - PURPOSE: HER2-dependent signalling pathway is deregulated in a subset of colon
      adenocarcinomas. Although HER2 protein expression patterns demonstrate a broad
      diversity in these tumors, the critical parameter for targeting the gene is the
      detection of gene amplification. Our aim was to investigate the correlation
      between HER2 protein levels and chromosome 17 (chr 17) copies. METHODS: Sixty
      paraffin-embedded samples of primary colon adenocarcinomas were cored at 1 mm
      diameter and transferred to the microarray block. Immunohistochemistry (IHC) was
      performed using anti-HER2 monoclonal antibody. Chromogenic in situ hybridization
      (CISH) was performed using HER2 gene/chromosome 17 centromeric probes. RESULTS:
      HER2 protein overexpression (score: 2+/3+) was observed in 20/60 (33.3%) samples.
      CISH analysis detected 11/60 (18.33%) amplified cases, whereas chromosome 17
      aneuploidy (polysomy) was identified in 13/60 (21.66%) cases. Significant
      associations were detected correlating HER2 expression with grade of the tumors
      (p=0.03), Chr 17 with stage (p=0.01), gene copies with protein expression
      (p=0.008), and also Chr 17 centromere signals with overall gene signals
      (p=0.001). CONCLUSION: Multiple HER2 gene copies lead to different protein
      expression patterns (score 1+ to 3+) but pure gene amplification is only a subset
      of them. Identification of chromosome polysomy is a critical parameter in
      detecting original gene amplification in conventional one-color CISH methods.

PMID- 24659652
TI  - Evaluation of erectile dysfunction risk factors in young male survivors of
      colorectal cancer.
AB  - PURPOSE: Improved long-term survival of colorectal cancer patients (CRC) treated
      with surgery and/or chemotherapy +/- radiotherapy (RT) has led to increased
      awareness of long-term side effects, including effecting sexual life, which can
      ultimately affect the quality of life in these patients. Because the absolute
      risk factors of erectile dysfunction (ED) have not been defined in CRC patients,
      the aim of this research was to identify the severity and the absolute risk
      factors of ED in male CRC survivors. METHODS: The medical records of 61 male
      survivors of CRC treated with surgery and/or chemotherapy +/- RT were retrieved
      from the medical oncology outpatient clinics during routine follow-up visits in
      2011-2012. Patients older than 55 years and those with ED history before
      diagnosis were excluded. International Index of Erectile Function (IIEF)
      questionnaire was filled in by the patients. RESULTS: The patient mean age was
      47.6+/-6.7 years (range 18-55) at the time of filling in the questionnaire.
      According to the International Index of Erectile Function (IIEF) score, 83.6% of
      the patients had some degree of ED. The risk factors of erectile dysfunction were
      advancing age (p=0.01), tumor location (p=0.01), type of surgery (p=0.02),
      presence of stoma (p=0.03)) and RT (p=0.005). Chemotherapy didn't impact ED
      (p=0.46). Also, there was no significant correlation between smoking status,
      hypertension, diabetes mellitus, cardiovascular disease, stage of the tumor and
      ED. Also hormonal disturbances such as serum FSH, LH and testesterone levels did
      not affect the presence of ED. CONCLUSION: Overall, 83.6% of the male CRC
      survivors had some degree of ED according to the IIEF. The risk factors of ED
      were advancing age, tumor location, type of operation, presence of stoma and RT.
      Clinicians should be aware of these risk factors to offer their patients adequate
      treatment options and also come up with new treatment strategies necessary to
      reduce further ED in CRC survivors.

PMID- 24659653
TI  - Does treatment interruption and baseline hemoglobin affect overall survival in
      early laryngeal cancer treated with radical radiotherapy? 10 years follow up.
AB  - PURPOSE: In this retrospective study we assessed different factors affecting the
      outcome of early laryngeal cancer, focusing on the impact of the pretreatment
      hemoglobin (Hb) level, time interval between diagnosis and start of radiotherapy,
      as well as treatment interruption during the course of radiotherapy. METHODS: We
      reviewed the hospital records, oncology database and radiotherapy treatment
      sheets of 88 patients with T1-T3 N0M0 squamous cell carcinoma of the larynx who
      had been treated with radical radiotherapy at Northamptonshire Centre for
      Oncology during the period from 1st January 1996 till 31st December 2002
      inclusive. Patients were followed up for 10 years. RESULTS: There were no
      significant overall survival differences with regard to sex , stage, radiotherapy
      dose received, treatment interruption for 1 to 2 days , as well as the delay to
      start radiotherapy (mean delay 57 days). However, there was statistically
      significant adverse overall survival outcome with increasing age (p<0.001). On
      the other hand, patients with pretreatment Hb level >12 g/dl had significant
      statistical overall survival benefit over those with <=12 g/dl (p=0.018).
      CONCLUSION: Pretreatment Hb level had a significant impact on overall survival in
      patients with early laryngeal carcinoma treated with radical radiotherapy. Time
      to start radiation treatment, treatment interruption for 1 or 2 days and
      different dose / fractionations did not affect the overall survival.

PMID- 24659654
TI  - The effect of nitidine chloride on the proliferation and apoptosis of
      nasopharyngeal carcinoma cells.
AB  - PURPOSE: This study was conducted to investigate the effect of nitidine chloride
      (NC) on the proliferation and apoptosis of nasopharyngeal carcinoma cell line
      CNE1, CNE2, TWO3, and C666-1, and to explore its antitumor mechanism. METHODS: NC
      was dissolved in IMDM medium and cultured with nasopharyngeal carcinoma cell line
      CNE1, CNE2, TWO3 and C666-1. Cell morphology, cell proliferation, cell apoptosis,
      p53 mRNA and p53 protein levels were assessed. RESULTS: After incubation with NC
      for 24 h, typical apoptotic morphology was observed. NC inhibited the
      proliferation and induced apoptosis of all 4 cell lines in a time-dose dependent
      manner. p53 mRNA and p53 protein levels were significantly increased.
      CONCLUSIONS: NC inhibited proliferation and induced apoptosis of nasopharyngeal
      carcinoma cells with upregulation of p53 gene.

PMID- 24659655
TI  - Ionizing radiation induces autophagy in human oral squamous cell carcinoma.
AB  - PURPOSE: Irradiation-induced autophagy has been reported in several types of
      cancers, however, the relationship between irradiation and autophagy in human
      oral squamous cell carcinoma (OSCC) has not yet been described. In this study we
      investigated the induction of autophagy in cell lines by exposing them to
      ionizing irradiation. METHODS: Human OSCC OC3 and SAS cell lines were used in
      this study. Cell viability and induction of autophagy were determined under
      irradiation treatment. The GFP-LC3 puncta formation and the levels of LC3-II as
      indicators of autophagy were detected by fluorescence microscopy and Western blot
      method. The signaling pathways involved in irradiation-mediated autophagy were
      also determined by Western blot method. RESULTS: Irradiation decreased cell
      viability only in OC3 cells, while autophagic machinery and related signaling
      pathways were found to be elevated after irradiation in OC3 and SAS cells.
      However, autophagic degradation determined by the reduction of p62 levels was
      only found in OC3 cells, suggesting autophagosome accumulation took place in SAS
      cells. In addition, irradiation accompanied with rapamycin treatment elevated
      autophagy formation and induced death of OC3 cells. CONCLUSIONS: These results
      suggested that induction of autophagy might provide an advantageous strategy to
      increase the anticancer effects of radiotherapy in patients with OSCCs.

PMID- 24659656
TI  - Suppression of STAT3 by chemically modified siRNAs increases the chemotherapeutic
      sensitivity of parental and cisplatin-resistant non-small cell lung cancer cells.
AB  - PURPOSE: Increased activation of the JAK-STAT signaling pathway is frequently
      observed in several primary cancers as well as cancer cell lines. Thus, targeting
      JAK-STAT pathway components by different molecular-biologic approaches in the
      search for new anticancer therapies has become widespread and resulted in
      encouraging outcomes. In this study, the effects of chemically modified anti
      STAT3 small interfering (si)RNAs on cell viability, proliferation and apoptosis
      of parental and cisplatin resistant non-small cell lung cancer (NSCLC) cells were
      investigated with the aim to provide a new therapeutic strategy for overcoming
      cisplatin resistance in lung cancer. METHODS: The parental NSCLC cell line Calu1
      and its cisplatin- resistant subline CR-Calu1 were used to study the effects of
      STAT3 suppression with chemically modified anti-STAT3 siRNAs. STAT3 gene and
      protein expressions were analyzed by real-time (RT) quantitative (q) PCR and
      Western blot, respectively. Apoptosis was evaluated by Caspase-3 activity and
      cell death assays. RESULTS: STAT3 messenger (m)RNA and protein expression were
      significantly increased in CR-Calu1 cells and suppressing its expression with
      specific siRNAs increased the rate of apoptosis through Caspase-3 activation.
      STAT3 suppression also significantly increased cisplatin sensitivity of Calu1 and
      CR-Calu1 cells after transfection with STAT3 siRNAs. CONCLUSIONS: NSCLC cells
      could be sensitized to cisplatin by targeting STAT3 with chemically modified
      siRNAs together, a fact which was accompanied with increased apoptosis.

PMID- 24659657
TI  - Neuron specific enolase and prognosis of non-small cell lung cancer: a systematic
      review and meta-analysis.
AB  - PURPOSE: The predictive and prognostic role of neuron-specific enolase (NSE) in
      non-small cell lung cancer (NSCLC) is still under debate. The present meta
      analysis aimed to evaluate the relation between serum NSE levels and the
      prognosis of NSCLC. METHODS: We performed a meta-analysis of published studies
      assessing the association of NSE with the prognosis of NSCLC. Literature
      retrieval, trials' selection and assessment, data collection, and statistical
      analysis were performed according to the Revman 5.0 guidelines. A fixed-effect
      model was used to pool the hazard ratio (HR) and 95% confidence intervals (95%
      CIs). RESULTS: A total of 8 eligible studies that included 2389 NSCLC patients
      were analyzed. We did not find prognostic value of NSE for NSCLC (HR=1.17, 95%
      CI: 0.95-1.44, p=0.14). CONCLUSION: The present study indicated that serum NSE
      level is of no prognostic significance in patients with NSCLC.

PMID- 24659658
TI  - Prognostic significance of protein kinase B/Akt pathway in patients with non
      small cell lung cancer.
AB  - PURPOSE: Akt, also known as protein kinase B (PKB), is an intracellular signal
      transduction protein activated by growth hormones. PKB/Akt is frequently
      activated in a variety of cancer types, but its role in the development and
      progression of lung cancer has not been completely elucidated yet. The aim of the
      present study was to determine the prognostic value of PKB/Akt in non-small cell
      lung cancer (NSCLC). METHODS: A total of 32 tumor samples from NSCLL patients
      were examined before treatment. The staining characteristics of the cases were
      evaluated in terms of age, stage (T and N), response to therapy, histological
      type, tumor size, and ECOG performance status (PS). RESULTS: No statistical
      correlation was found between PKB/ Akt expression and gender, ECOG PS and stage
      (T and N), while significant correlation between cytoplasmic PKB/akt expression
      and age was detected (p<0.05). In addition, squamous cell carcinoma histology was
      significantly associated with both nuclear and cytoplasmic staining (p=0.033),
      and tumor size ( <5 cm) was correlated with nuclear PKB/Akt expression (p=0.03).
      Both overall survival (OS) and progression- free survival (PFS) were similar in
      patients with and without both nuclear and cytoplasmic PKB/Akt expression.
      CONCLUSION: Our results showed that although PKB/Akt was not associated with
      survival in NSCLC patients, it may be a potential therapeutic target for NSCLC;
      more studies with higher numbers of patients are needed to verify this
      hypothesis.

PMID- 24659660
TI  - Primary cutaneous lymphomas: single center experience of dermatology and
      hematology clinics.
AB  - PURPOSE: To present the clinical characteristics, treatments performed, response
      to treatment, and follow up of 40 patients diagnosed with primary cutaneous
      lymphoma. METHODS: In this retrospective study included were 23 males and 17
      females from our center with confirmed diagnosis of primary cutaneous lymphoma
      over an 8-year period. Data were retrieved from the patient medical records.
      RESULTS: The median patient age at diagnosis was 59.5 years (range 33-86). Skin
      biopsies showed that 31 patients (77.5%) had mycosis fungoides (MF), 2 (5%) had
      anaplastic large cell lymphoma, 3 (7.5%) had diffuse large B cell lymphoma, 3
      (7.5%) had poikilodermic mycosis fungoides, and 1 (2.5%) had non-classified non
      Hodgkin lymphoma (NHL). In patients with T cell lymphoma clinical stage IA
      prevailed (42.5%). The 3 patients with B cell lymphoma had stage IE and 2 of them
      had B symptoms. Sezary cells were detectable in the peripheral blood of 3
      patients. Twenty-three patients (57.5%) used only topical corticosteroids, 2 (5%)
      were treated with PUVA (psoralen ultraviolet A), 1 (2.5%) was treated with PUVA
      and chemotherapy, 8 (20%) received combination chemotherapy, 1 patient (2.5%)
      received PUVA+ interferon+topical nitrogen mustard, and 1 (2.5%) received
      chemotherapy+topical nitrogen mustard+interferon. Among 16 patients with the
      valuable response to treatment 5 (33%) showed complete remission (CR) and 9 (60%)
      partial remission (PR). The median follow up time for all patients was 1.5 months
      (range 1-135). While mean overall survival (OS) time was 123 months (95% CI 100.6
      145.3), the estimated median OS was not reached. CONCLUSION: Early diagnosis of
      MF is rather favorable in terms of high and long-term response rates to topical
      treatments.

PMID- 24659659
TI  - Clinical characteristics, treatment and survival outcomes in malignant pleural
      mesothelioma: an institutional experience in Turkey.
AB  - PURPOSE: To compare treatment modalities and investigate potential prognostic
      factors for survival in patients with malignant pleural mesothelioma (MPM).
      METHODS: The present study has investigated the data of 150 patients with MPM who
      were examined and treated in our center from 2005 to 2012. RESULTS: The study
      included 87 male (58% and 63 female (42) patients. Surgical resection
      (pleurectomy/decortications (P/D), and extrapleural pneumonectomy (EPP)) was
      performed in 32 (36.7%) patients; 87 patients (58%) received chemotherapy alone
      and 16 (10.7%) had surgery, chemotherapy and radiotherapy (trimodal treatment).
      The median progression free and overall survival (PFS and OS) for all patients
      were 10.6 and 14.8 months, respectively. No statistically significant difference
      was observed between the patients who received pemetrexed/cisplatin (N=54) and
      gemcitabine/cisplatin (N=28) in terms of PFS and OS (p=0.145, p=0.244,
      respectively). Also, no statistically significant difference was registered
      between operated and non operated patients (PFS and OS, p=0.416, p=0.095,
      respectively). There was no difference in both PFS and OS rates between patients
      who had P/D or EPP (p=0.87, p=0.652, respectively). Log rank analysis: Eastern
      Cooperative Oncology Group performance status (ECOG PS) (p=0.018), histology
      (p<0.001), stage (p<0.001) and leukocytosis (p=0.005) were found to be
      significant prognostic factors of OS. At multivariate analysis, ECOG PS (p=0.016)
      and stage (p<0.001) were independent prognostic factors for OS. CONCLUSION:
      Median OS was approximately 1 year. ECOG PS, histological type, stage and
      presence of leukocytosis were prognostic factors that affected both PFS and OS.
      EPP or P/D surgical options did not provide difference in terms of survival.
      Survival rates in patients who received a combination of platinum analogues with
      pemetrexed or gemcitabine as front-line chemotherapy were similar.

PMID- 24659661
TI  - Pretreatment risk factors for overall survival in patients with gastrointestinal
      and non-gastrointestinal mucosa associated lymphoid tissue lymphomas.
AB  - PURPOSE: The aim of this 10-year retrospective study was to investigate
      prognostic clinical and laboratory factors significant for the outcome of
      patients with mucosa associated lymphoid tissue (MALT) lymphoma. METHODS: The
      study involved 87 patients diagnosed with MALT lymphoma: 37 (42.5%) with
      gastrointestinal (GI) and 50 (57.5%) with non-GI localization. The following
      pretreatment laboratory parameters were analyzed: hemoglobin, serum albumin and
      lactate dehydrogenase (LDH) level, beta2-microglobulin (bgr;2-M) and
      bacteriological (H.pylori) status. Estimated clinical features were: stage of
      disease, ECOG performance status (PS), tumor mass, number of extranodal
      localizations, presence of B symptomatology, splenomegaly and enlarged lymph
      nodes. Diagnosis of MALT lymphoma was based on histopathological analysis of
      tissue samples, obtained by endoscopy or surgery. RESULTS: The median disease
      free survival (DFS) was 36 months and the 5-year overall survival (OS) was 64%.
      OS rate of patients with non-GI localization was higher compared with patients
      with GI localization (p=0.001). Multivariate analysis showed hypoalbuminemia to
      be the most significant parameter associated with poor OS (p<0.001) for both
      patient groups. The most significant prognostic factor for poor OS in patients
      with GI localization was LDH level (p=0.031), while hypoalbuminemia was the most
      significant prognostic factor for poor OS in the group with non-GI disease
      localization (p=0.001). CONCLUSION: Proper therapeutic approach for MALT lymphoma
      patients could be planned taking into consideration poor prognostic parameters,
      i.e. hypoalbuminemia and elevated LDH for GI patients and hypoalbuminemia for non
      GI lymphoma patients.

PMID- 24659662
TI  - Capsaicin induced apoptosis and gene expression dysregulation of human acute
      lymphoblastic leukemia CCRF-CEM cells.
AB  - PURPOSE: Capsaicin, an ingredient of red chili pepper, has possible
      tumorigenicity/genotoxicity properties. We aimed to determine the effects of
      capsaicin on the proliferation and gene expression profiles of acute
      lymphoblastic leukemia (ALL) CCRF-CEM cell line. METHODS: Cell viability and IC50
      dose was determined by WST cytotoxicity assay. qRT-PCR, immunohistochemical
      staining and western blot methods were used to determine target genes' expression
      levels. Apoptosis was evaluated by measuring the caspase-3 activity. RESULTS:
      Capsaicin inhibited the proliferation of CCRFCEM cells in a dose-dependent
      manner. Increased mRNA expressions of caspase gene family members, activated
      caspase-3 and decreased mRNA and protein expression of BCL-2 gene indicated
      apoptotic response to capsaicin. Moreover capsaicin treatment suppressed
      significantly the expression of the key cell signaling pathways of KRAS, AKT,
      GAB2, PTPN11, BRAF, INPP5D, MAPK7. CONCLUSION: Capsaicin induces apoptosis in
      CCRF-CEM cells and this response is associated with downregulation of cell
      signaling pathways.

PMID- 24659663
TI  - Serum levels of cytokines and prevalence of autoantibodies in lymphoma patients
      and their prognostic value.
AB  - PURPOSE: Recent studies have shown that cytokines and autoantibodies that have an
      important role in pathogenesis of lymphoma can be used as prognostic markers. In
      this study, we aimed to determine the prognostic significance of a large panel of
      serum cytokines and compare them with a control group, and also to see for any
      relationship with known classical prognostic factors, the frequency of
      autoantibody positivity and autoimmune phenomena in patients with untreated non
      Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). METHODS: For cytokine
      studies blood samples were obtained in the morning after fasting for at least 8
      12 h. We used empty tubes for serum and EDTA-containing tubes for plasma samples.
      Blood samples were then transferred to laboratory in 5-10 min, plasma and sera
      were separated by centrifugation, and stored at -75 ?C until assayed. Then, all
      sera were warmed to room temperature. All the cytokine levels were studied with
      Panomics Company ProcartaTM Human Cytokine multiplex kits. RESULTS: In lymphoma
      patients INF-ggr; was related with thyroglobulin antibody positivity and IL-6
      with direct Coombs positivity. IL-6 was the most important cytokine connected
      with lymphopenia and B symptoms in lymphoma patients. IL-1beta, INF-gamma, IL-2
      and IL-4 were markers associated with poor prognosis in HL. At least one
      autoantibody was positive in 50% of NHL and HL patients. At least one
      antiphospholipid antibody (APA) was positive in 26% of NHL and 38% of HL
      patients. CONCLUSION: TNF-alpha and IL-6 are poor prognostic factors that may be
      included in the International Prognostic Index (IPI). To understand the effects
      of autoantibodies in the prognosis of HL and NHL, long-term patient follow-up
      studies are required.

PMID- 24659664
TI  - The prognostic role of preoperative serum CA 125 levels in patients with
      endometrial carcinoma.
AB  - PURPOSE: Previous studies have shown that elevated preoperative serum CA 125
      levels strongly correlate with various clinical and pathological variables and
      prognosis of patients with endometrial carcinoma (EC). The aim of the present
      study was to evaluate the clinical significance of preoperative serum CA 125
      levels in patients with EC. METHODS: A retrospective study of all EC patients
      treated at our institution between 1995 and 2010 with available follow-up was
      conducted. The preoperative serum level of CA 125 was measured in 99 patients and
      evaluated in relation to various clinical and pathological variables and outcome.
      We used the cut-off level of 20 U/ml for CA 125 on chi-square test for
      categorical variables. Survival analysis was performed with the use of Kaplan
      Meier method, the log rank test and Cox proportional hazards regression analysis.
      RESULTS: In the early stages of disease the mean values of CA 125 were 35 U/ml
      (SD+/-70) for stages IA-IB and 21 U/ml (SD+/-29) for stage IC (Mann-Whitney test
      for continuous variables). In advanced stages of disease (III-IV), the values of
      preoperative serum CA 125 levels were statistically increased, with mean value 54
      U/ml (SD+/-44), in comparison to stages IA-IB (p=0.02) and IC (p=0.007).
      According to the multivariate analysis, elevated preoperative serum CA 125 level
      (p=0.043) and histological tumor type (p=0.004) were independent prognostic
      factors for disease free survival (DFS) and overall survival (OS) of patients
      with EC. CONCLUSION: The current study suggests that measurement of preoperative
      serum CA 125 is a useful clinical tool in the prognosis of patients with EC.

PMID- 24659665
TI  - Expression of Sox2 in cervical squamous cell carcinoma.
AB  - PURPOSE: Sox2, one of the genes that maintains self-renewal of embryonic stem
      cells and relates to the differentiation potential of these cells, is abnormaly
      expressed in various human tumors. We investigated the expression Sox2 in normal
      cervix and cervical squamous cell carcinoma (SCC), and we also assessed the
      prognostic significance of Sox2 expression in FIGO stage I-II cervical SCC.
      METHODS: Immunohistochemistry was performed to define the expression of Sox2 in
      20 normal cervical tissue samples and 55 samples of cervical SCC. Correlations
      with clinicopathological characteristics were determined by chi-square test. The
      prognostic impact of Sox2 expression with regard to overall disease-free survival
      (DFS) was determined by the Kaplan-Meier method. RESULTS: The positive expression
      rate in cervical SCC was 74.5% (41/55), while in normal cervix it was 20.0%
      (4/20; p=0.000. In addition, the expression of Sox2 did not correlate with
      clinical factors (p>0.05). The overall DFS rates with negative and positive
      expressions of Sox2 were 35.7 and 29.3%, respectively (p=0.360). CONCLUSIONS: Our
      results show that Sox2 was overexpressed in FIGO stage I-II cervical SCC,
      indicating that overexpressed Sox2 may play an important role in the
      carcinogenesis of cervical SCC. Besides, we found that the expression of Sox2 had
      no relation to clinical factors and prognosis.

PMID- 24659666
TI  - WNT1 gene expression alters in heterogeneous population of prostate cancer cells;
      decreased expression pattern observed in CD133+/CD44+ prostate cancer stem cell
      spheroids.
AB  - PURPOSE: Established cancer cell lines contain cancer stem cells (CSCs) which can
      propagate to form three dimensional (3D) tumor spheroids in vitro. Aberrant
      activation of WNT signaling is strongly implicated in the progression of cancer
      and controls CSCs properties. In this study we hypothesized that when cells were
      maintained as spheroids, the structure of CSCs could show differentiation between
      CSCs and non- CSCs. METHODS: CD133+/CD44+ cancer-initiating cells were isolated
      from DU-145 human prostate cancer cell line monolayer cultures, propagated as
      tumor spheroids and compared with the remaining heterogeneous cancer cells bulk
      population. The expression levels of WNT1, FZD1, ADAR, APC, AXIN, BTRC, FRAT1 and
      PPARD genes were measured by polymerase chain reaction (PCR) array assay and the
      protein expression levels of WNT1, FZD and AXIN by immunohistochemistry. RESULTS:
      The expression levels of WNT pathway-related molecules were found to increase in
      both CSCs and non- CSCs when CSCs were maintained as spheroids. However,
      different expression profiles were observed when CSCs and non-CSCs were compared.
      In spheroids, the expression levels of FZD1, APC, ADAR, WNT1, PPARD genes in CSCs
      decreased when compared to non-CSCs. Interestingly, when CSCs from spheroids were
      compared with CSCs from monolayers the most significant decrease was observed in
      FZD1 and increase in APC genes. CONCLUSION: It is possible to assume that
      intracellular signaling of WNT-related molecules in the nucleus and/or cytoplasm
      might play an important role but it is independent from increased ligand
      expression and this expression strongly differentiate CSCs and non-CSCs
      population. This unexpected expression could be important for CSCs behavior and
      targeting this pathway could have therapeutic implications in cancer.

PMID- 24659667
TI  - Expression of hepatocyte growth factor activator inhibitor-1 (HAI-1) gene in
      prostate cancer: clinical and biological significance.
AB  - PURPOSE: Hepatocyte growth factor activator inhibitor type-1 (HAI-1) is an
      integral-membrane proteinase inhibitor. Some studies have shown that HAI-1 as a
      matriptase inhibitor that plays a significant role in regulating cancer
      progression and metastasis. In this study, we attempted to clarify whether the
      levels of HAI-1 could be a useful marker in patients with prostate cancer (Pca).
      METHODS: HAI-1 protein was evaluated by immunohistochemistry (IHC) and HAI-1 mRNA
      was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 48
      patients with Pca and 20 patients with benign prostate hyperplasia (BPH). The
      association between HAI-1 and clinicopathological features and survival were
      analyzed. RESULTS: A high level of HAI-1 protein and mRNA expression was detected
      in BPH compared to Pca specimens. The HAI-1 expression inversely correlated with
      Gleason score and pathological stage (p<0.05). It was significantly stronger in
      N0M0 tumors than in N+ or M+ tumors (p<0.05). Furthermore, low HAI-1 expression
      was a significant predictor for poor prognosis when compared with high HAI-1
      expression (disease-free survival/DFS rate, p=0.0487; overall survival/ OS rate;
      p=0.0492). CONCLUSION: The results of the present study identified HAI-1 as a
      favorable prognostic marker for Pca and may indicate that HAI-1 could be a
      therapeutic target for the treatment of this malignancy.

PMID- 24659668
TI  - A study of Smad4 and Smad7 expression in surgically resected samples of gastric
      adenocarcinoma and their correlation with clinicopathological parameters and
      patient survival.
AB  - PURPOSE: The canonical signaling pathway for the transforming growth factor-beta
      (TGF-beta) family is through the Smad proteins which are pivotal intracellular
      mediators of TGF-beta family members. Recently, disruption of the TGF-beta
      pathway in cancer has been demonstrated at the level of the Smad signal
      transducers. In this study, we examined Smad4 and Smad7 expression in gastric
      carcinomas to elucidate their role in tumor progression. METHODS: The
      immunohistochemical expression of Smad4 and Smad7 was evaluated in 151 surgically
      resected samples of gastric adenocarcinoma in order to examine their correlation
      with clinicopathologic findings and patients' survival. RESULTS: Smad4 and Smad7
      expression (low, moderate or strong) was observed in 86.7% (131/151) and 33.1%
      (50/151) of gastric adenocarcinoma tumor samples, respectively. Our results
      revealed that the loss of Smad4 expression correlated significantly with the
      intestinal type, male sex, depth of tumor and poor survival. Smad7 expression was
      significantly more frequent in intestinal type and well differentiated gastric
      adenocarcinomas and significantly correlated with the duration of disease-free
      survival. CONCLUSION: Smad signal transducers are considered as important
      molecules in tumor development and progression and the evaluation of their
      expression in human gastric cancer could be useful in selecting stage I patients
      who should be considered as candidates for adjuvant chemotherapy.

PMID- 24659669
TI  - MicroRNA-21 stimulates gastric cancer growth and invasion by inhibiting the tumor
      suppressor effects of programmed cell death protein 4 and phosphatase and tensin
      homolog.
AB  - PURPOSE: MicroRNA-21 (miR-21) is abnormally expressed in many solid cancers, such
      as gastric adenocarcinoma, and regulates some targets involved in cancer
      initiation and progression. In this study, we investigated the function of miR-21
      in two gastric cancer cell lines, as well as its potential targeting of the tumor
      suppressor genes phosphatase and tensin homolog (PTEN) and programmed cell death
      protein 4 (PDCD4). METHODS: The first step was to use quantitative (q) RTPCR in
      order to verify the overexpression of miR-21 in two different gastric cancer cell
      lines (SGC-7901 and MKN-45) transfected with mIR-21 mimic. Western blotting
      confirmed the qRT-PCR data in a set of rescue experiments in which miR-21 mimic,
      inhibitor, and non specific mimic (NSM) were used to transfect the two gastric
      cancer cell lines. The protein levels of miR-21 targets PTEN and PDCD4 were
      estimated. Then, we evaluated its effect on tumor growth and invasion potential
      on the two different gastric adenocarcinoma cell lines. RESULTS: qRT-PCR results
      proved that miR-21 was overexpressed in gastric cancer cells transfected with miR
      21 mimic. Western blot results further suggested that PTEN and PDCD4 were
      regulated by miR-21, as miR-21 inhibitor increased the expression of PTEN and
      PDCD4 proteins and significantly reduced cell proliferation, migration and
      invasion. In the control experiment miR-21 mimic significantly inhibited the
      expression of PTEN and PDCD4 proteins in the two gastric cell lines, leading to
      an increase in cell invasion and migration. Furthermore, miR-21 mimic inhibited
      the apoptosis of the two gastric cancer cell lines. CONCLUSIONS: miR-21 is
      overexpressed in gastric cancer and its aberrant expression may have important
      role in gastric cancer growth and dissemination by modulating the expression of
      the tumor suppressors PTEN and PDCD4, as well as by modulating the pathways
      involved in mediating cell growth, migration, invasion and apoptosis. Targeting
      miR-21 may help develop novel therapeutics for gastric cancer, once its
      pathophysiology is completely investigated.

PMID- 24659670
TI  - Does the computed tomography perfusion imaging improve the diagnostic accuracy in
      the response evaluation of esophageal carcinoma to the neoadjuvant
      chemoradiotherapy? Preliminary study.
AB  - PURPOSE: To estimate whether the computed tomography (CT) perfusion imaging could
      be useful to predict the pathological complete response (pCR) of esophageal
      cancer to the neoadjuvant chemoradiotherapy (NACRT). METHODS: Twenty-seven
      patients with the advanced squamous cell esophageal carcinoma, who were treated
      with concomitant CRT (CIS/5-FU/LV and 45-50 Gy total radiation dose), were re
      evaluated using CT examination, which included the low-dose CT perfusion study.
      CT perfusion series were analysed using the deconvolution-based CT perfusion
      software (Perfusion 3.0, GE), and color parametric maps of the blood flow (BF),
      blood volume (BV), mean transit time (MTT), and permeability surface area product
      (PS) were displayed. All patients were operated and histopathological analysis of
      the resected esophagus considered the gold standard for pathologic complete
      response (pCR). RESULTS: BFpost-NACRT, BVpost-NACRT, and PSpost-NACRT were
      significantly lower, and MTTpost-NACRT significantly higher in the pCR group.
      Mean (+/-SD), or median perfusion parameter values in the pCRs (11 patients) vs
      non-pCRs (16 patients) were: BFpost-NACRT- 21.4+/-5.0 vs 86.0+/-29 ml/min/100 g
      (p<0.001), BVpost-NACRT- 1.3 vs 3.9 ml/100 g (p<0.001), MTTpost-NACRT- 5.5 vs 3.7
      s (p=0.018), and PSpost-NACRT- 5.9 vs 9.8 ml/min/100 g (p=0.006). ROC analysis
      revealed that BFpost- NACRT (AUC=1.000), BVpost-NACRT (AUC=0.932), MTTpost-NACRT
      (AUC=0.801), and PSpost-NACRT (AUC=0.844) could predict the pCR (p<0.01), while
      maximal esophageal wall thickness could not (AUC=0.676, p=0.126). If we set a cut
      off value of BFpost-NACRT<30.0 ml/min/100 g, pCR was predicted with sensitivity
      and specificity of 100%. CONCLUSION: CT perfusion imaging enables accurate
      prediction of pCR of esophageal carcinoma to neoadjuvant chemoradiotherapy.

PMID- 24659671
TI  - p95-HER2 and trastuzumab resistance in metastatic breast cancer; is
      immunohistochemistry appropriate?
AB  - PURPOSE: Unraveling the mechanisms underlying the resistance to trastuzumab is
      important for amending the prognosis of patients with human epidermal growth
      factor receptor 2 (HER2) positive metastatic breast cancer. Experimentally, it
      has been shown that p95-HER2 positive breast tumors are resistant to trastuzumab.
      The aim of this study was to investigate the predictive and prognostic importance
      of p95-HER2 expression by immunohistochemistry in HER2-positive metastatic breast
      cancer patients treated with trastuzumab. METHODS: Only patients who had a
      histological diagnosis of HER2-positive metastatic breast cancer and who had
      received first line therapy containing trastuzumab were enrolled in the study.
      Immunohistochemistry was used to analyze p95-HER2 expression in the tissue blocks
      of the patients. RESULTS: The study was performed on 38 patients aged between 30
      and 84 years. In 14 patients (36.8%), p95-HER2 was positive, whereas it was
      negative in the remaining 24 patients (63.2%). There was no significant
      correlation between p95-HER2 expression and overall survival, response to
      trastuzumab, and progression-free survival (PFS). CONCLUSION: Unlike previous
      reports, there was no correlation between the p95-HER2 expression and resistance
      to trastuzumab. It may be argued that an analysis using immunohistochemistry is
      inadequate for determining p95- HER2. In order to ascertain whether
      immunohistochemistry is an appropriate method, studies with larger patient groups
      are needed.

PMID- 24659672
TI  - Stereotactic radiosurgery in patients with multiple intracranial meningiomas.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) delivers a potent, highly focused dose
      of radiation to the tumor while sparing the surrounding normal tissues. The
      purpose of this study was to assess the outcome of patients with intracranial
      meningiomas treated with SRS. METHODS: A total of 73 patients with 221 benign
      meningiomas treated between 1991 and 2005 with SRS and followed up for more than
      a year were reviewed. Fifty patients (68%) were treated with SRS to the primary
      meningioma while 23 (32%) received SRS to relapsing tumors adjacent or distant
      from the site of the initial meningioma that was previously treated with surgery
      alone. Mean tumor margin dose was 14 Gy (range 10-16). SRS was delivered after
      surgery in 117 meningiomas (55 patients). RESULTS: The median age at diagnosis
      was 47 years (range 16-74) and the median follow-up 5.8 years (range 1-13.6). The
      3- and 5-year overall survival (OS) rates for all patients were 95% and 90%,
      respectively. The mean gross tumor volume decreased from 4.17 cm3 to 3.23 cm(3)
      after SRS (p=0.057). Twenty-two (10%) meningiomas increased after SRS. In
      addition, clinical symptoms improved in 36% and remained stable in 45% of the
      patients. With regard to morbidity of SRS, only 7 patients (9.6%) had late
      complications, including edema (N=4), brain necrosis (N=4), gliosis (N=1), and
      paresis of the III pair nerve (N=1). There was no treatment-related mortality.
      CONCLUSION: SRS for patients with multiple intracranial meningiomas is effective
      yielding a high rate of local tumor control, whereas treatment-related morbidity
      remains low.

PMID- 24659673
TI  - Radiofrequency ablation assisted resection for hepatocellular carcinoma:
      morbidity, mortality and long term survival.
AB  - PURPOSE: Hepatic resection is the mainstay of the curative treatment of primary
      hepatic tumors, with constantly improving short and long term results.
      Radiofrequency ablation (RFA)-assisted liver resection is a relatively new method
      of transection of the liver parenchyma with favorable intra- and perioperative
      results. The aim of this study was to investigate the oncological efficacy (long
      term overall survival/OS and disease free survival/DFS) and to confirm the
      favorable short term morbidity and mortality. METHODS: Between May 2004 and
      January 2007, 28 patients underwent 32 resections with removal of 50
      hepatocellular carcinoma (HCC) lesions. The technique of parenchymal transection
      has been described previously as RFA-assisted liver resection. RESULTS: Thirty
      day morbidity and mortality were 42.8 and 0%, respectively. Blood transfusion was
      necessary for 28.5% of the patients. The median hospital stay was 16.5 days
      (range 5-34). The 1- and 3-year OS were 92.9 and 65.7%, respectively. The 1- and
      3-year DFS were 62.3 and 54.6- respectively. No patient developed metastatic
      disease or local recurrence at the margin site. Twelve patients (42.9%) developed
      in-the-liver recurrence away from the resection area. CONCLUSION: RFA-assisted
      liver resection is a safe and oncologically efficacious method for the surgical
      treatment of HCC with results comparable to other surgical techniques.

PMID- 24659674
TI  - Sentinel lymph node biopsy for cutaneous melanoma: a propos of 144 cases.
AB  - PURPOSE: The aim of this study was to identify the predictive factors of a
      positive sentinel lymph node (SLN) in patients with cutaneous malignant melanomas
      and tumor progression. METHODS: From October of 2000 to January of 2006, 144
      patients with cutaneous malignant melanoma underwent SLN biopsy. Patients were
      divided into two groups according to the SLN status (positive vs negative) which
      were compared with regards to patient demographics and primary tumor
      characteristics. RESULTS: In 37 (25.69%) patients SLN biopsy was positive .
      Nodular melanomas (p=0.047), blood (p=0.010) and lymph (p<0.001) vessel
      infiltration, mitotic rate (p=0.019) and Breslow thickness (p=0.012) were
      predictive of a positive SLN biopsy. The overall recurrence, mortality and the
      overall disease free survival (DFS) rates were 6.25, 1.4 and 93.75, respectively.
      CONCLUSION: SLN biopsy is the most important predictor of early disease
      recurrence and survival in patients with cutaneous malignant melanoma.
      Considering all the examined factors, a positive SLN biopsy is related with
      Breslow thickness and lymph vessel infiltration.

PMID- 24659675
TI  - Cancer mortality in central Serbia.
AB  - PURPOSE: Cancer is the one of the leading cause of death worldwide. The aim of
      this study was to examine cancer mortality trends in the population of central
      Serbia in the period from 2002 to 2011. METHODS: The descriptive epidemiological
      method was used. The mortality from all malignant tumors (code C00-C96 of the
      International Disease Classification) was registered. The source of mortality
      data was the published material of the Cancer Registry of Serbia. The source of
      population data was the census of 2002 and 2011 and the estimates for inter
      census years. Non-standardized, age-adjusted and age-specific mortality rates
      were calculated. Age adjustment of mortality rates was performed by the direct
      method of standardization. Trend lines were estimated using linear regression.
      RESULTS: During 2002-2011, cancer caused about 20% of all deaths each year in
      central Serbia. More men (56.9%) than women (43.1%) died of cancer. The average
      mortality rate for men was 1.3 times higher compared to women. A significant
      trend of increase of the age-adjusted mortality rates was recorded both for males
      (p<0.001) and for females (p=0.02). Except gastric cancer, the age-adjusted
      mortality rates in men were significantly increased for lung cancer (p=0.02),
      colorectal cancer (p<0.05), prostate cancer (p=0.01) and pancreatic cancer
      (p=0.01). Age-adjusted mortality rates for breast cancer in females were
      remarkably increased (p=0.01), especially after 2007. CONCLUSIONS: In central
      Serbia during the period from 2002 to 2011, there was an increasing trend in
      mortality rates due to cancers in both sexes. Cancer mortality in males was 1.3
      fold higher compared to females.

PMID- 24659676
TI  - Informing cancer patient based on his type of personality: the uninvolved - aloof
      patient.
AB  - Communicating bad news is often part of a doctor's task. By bad news we mean
      information which is received as unpleasant by the patient who feels that it can
      have an unwanted effect in his life. It appears that the way each patient
      assesses bad news is associated with his personality type, his individual
      character traits and the adoption of an empathic approach is vital within a
      therapeutic relationship. The aim of this article was to describe the uninvolved
      aloof character or type of personality thoroughly so that any therapist can make
      a diagnosis and tailor the information strategy to the patient's needs. As method
      of research was used the qualitative method through groups with doctors and
      nurses, while research within groups lasted for 5 years. Assessing the denial
      mechanism may present the hardest task since the patient does not give any hint
      to the doctor as to how he feels. The degree of informing should be not as much
      as for the controlling-orderly person but more than the dependent person's, about
      "average" to "small". Informing Family: He accepts the family's involvement.
      Relatives need to be alerted about the patient's fragility. 

PMID- 24659677
TI  - Antioxidative and antiproliferative evaluation of 2
      (phenylselenomethyl)tetrahydrofuran and 2-(phenylselenomethyl)tetrahydropyran.
AB  - PURPOSE: To determine the antioxidant and antiproliferative influence of 2
      (phenylselenomethyl)tetrahydrofuran (1a) and 2
      (phenylselenomethyl)tetrahydropyran (2a) on colon cancer cell line HCT-116 and
      breast cancer cell line MDA-MB-231. METHODS: Cell viability was monitored in a
      dose-dependent manner using MTT assay. The concentration of superoxide anion
      radical (O2 *(-)) was determined spectrophotometrically. Spectrophotometric
      determination of nitrites (NO2 -) was performed by using the Griess method.
      Determination of total glutathione (GSH) was also performed
      spectrophotometrically. RESULTS: HCT-116 cell line was more sensitive to the
      effects of the investigated substances than MDA-MB-231 cell line. Also, it was
      noticed that 1a produced greater effect compared to 2a. Moreover, both
      investigated compounds decreased to a certain degree the oxidative stress by
      decreasing the O2*(-) and thus the peroxynitrite concentration. At the same time,
      1a and 2a acted more efficiently in promoting the endogenous antioxidative
      capacities (increased GSH concentration) providing better self-defence
      capabilities for cells. CONCLUSION: Our findings showed that the investigated
      selenium compounds play an important role in reducing the levels of reactive
      oxygen species (ROS); therefore, we believe that, as antioxidants, they could
      prevent the processes arising as a consequence of oxidative stress, including
      cancer.

PMID- 24659678
TI  - Is (99m)Tc-MDP whole body bone scintigraphy adjuvant to (18)F-FDG-PET for the
      detection of skeletal metastases?
AB  - PURPOSE: Due to the fact that fluorine-18-fluorodeoxyglucose positron emission
      tomography/computed tomography ((18)F-FDG-PET/CT) and technetium-99m
      methylenediphosphonate ((99m)Tc-MDP) whole body scans identify bone metastases by
      different mechanisms, i.e. by using glucose metabolism and osteoblastic response
      in the bone, respectively, it can be expected that there may be some differences
      between these two methods in the number of lesions identified. The aim of this
      study was to compare the sensitivity, specificity, accuracy, positive predictive
      value (PPV) and negative predictive value (NPV) in detecting bone metastases
      between (18)F-FDG-PET/CT and conventional (99m)Tc-MDP whole body scans. METHODS:
      Between 2006-2009, 121 patients with malignancies (62 male and 59 female, mean
      age 59.3+/-10.8 years, range 37-84) were examined with (18)F-FDG-PET/CT and
      conventional (99)Tc-MDP whole-body scans for detection of bone metastases.
      RESULTS: For (18)F-FDG-PET/CT and for (99m)TC-MDP, sensitivity, specificity,
      accuracy, PPV and NPV for detecting all studied bone metastases were 88.3, 83.6,
      86.7, 91.7, 77.8% and 91.7, 71.0, 84.9, 86.6, 80.8%, respectively. For bone
      metastases of breast and lung cancers, the specificity and accuracy of PET/CT was
      higher than that of bone scintigraphy. On the other hand, the sensitivity of bone
      scintigraphy was higher than PET/CT in breast and lung cancers groups and all
      patients. In the detection of osteolytic and osteosclerotic metastases no
      difference was found between the two methods, while for osteolytic lesions the
      mean standardized uptake value (SUV) max was higher than for osteosclerotic
      lesions. CONCLUSION: For the detection of bone metastases the specificity and
      accuracy of (18)F-FDG-PET/CT were higher compared to bone scintigraphy, while the
      sensitivity was lower. It is the opinion of the authors that both studies are
      complementary to final diagnosis.

PMID- 24659679
TI  - Quantification of uncertainties in conventional plan evaluation methods in
      Intensity Modulated Radiation Therapy.
AB  - PURPOSE: In Intensity Modulated Radiation Therapy (IMRT) dose distributions tend
      to be more complex and heterogeneous because of the modulated fluences in each
      beamlet of every single beam. These dose-volume (DV) parameters derived from the
      dose volume histogram (DVH) are physical quantities, thought to correlate with
      the biological response of the tissues. The aim of this study was to quantify the
      uncertainty of physical dose metrics to predict clinical outcomes of
      radiotherapy. METHODS: The radiobiological estimates such as tumor control
      probability (TCP) and Normal Tissue Complication Probability (NTCP) were made for
      a cohort of 40 cancer patients (10 brain;19 head & neck;11 cervix) using the DV
      parameters. Statistical analysis was performed to determine the correlation of
      physical plan quality indicators with radiobiological estimates. RESULTS: The
      correlation between conformity index (CI) and TCP was found to be good and the
      dosimetric parameters for optic nerves, optic chiasm, brain stem, normal brain
      and parotids correlated well with the NTCP estimates. A follow up study (median
      duration 18 months) was also performed. There was no grade 3 or 4 normal tissue
      complications observed. Local tumor control was found to be higher in brain (90%)
      and pelvic cases (95%), whereas a decline of 70% was noted with head & neck
      cancer cases. CONCLUSIONS: The equivalent uniform dose (EUD) concept of
      radiobiological model used in the software determines TCP and NTCP values which
      can predict outcomes precisely using DV data in the voxel level. The uncertainty
      of using physical dose metrics for plan evaluation is quantified with the
      statistical analysis. Radiobiological evaluation is helpful in ranking the rival
      treatment plans also.

PMID- 24659680
TI  - Transcriptional profiling of erythroid progenitors from G-CSF mobilized and
      nonmobilized peripheral blood.
AB  - PURPOSE: The purpose of this study was to examine the gene expression profile of
      granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood (mPB)
      derived progenitors, used in transplantation. METHODS: We correlated gene
      expression patterns of highly enriched steady-state peripheral blood (PB)- and
      mPB-derived CD71+ cells by microarray and ingenuity pathway analyses, to identify
      the transcriptional program during in vitro erythroid differentiation. RESULTS:
      The gene expression was more than doubled in mPB-derived (4180 genes) compared to
      PB-derived erythroid progenitors (1667 genes) while PB-and mPB-derived erythroid
      progenitors shared 1534 common genes. Comparative analysis of transcript levels
      showed differential expression of 54 genes between cultured erythroid progenitors
      of PB and mPB origin, where we identified common 13 downregulated and 30
      upregulated genes. The most significant genes in mPB-derived erythroid
      progenitors were P4HB, DDIA3, ARPC2 and ATP5G3. Regarding G-CSF stimulation the G
      CSF receptor CSF2RB (1.1-fold) was linked via STAT3 to erythroid-specific ALAS2
      (2.9-fold) and GATA2 (1.3-fold) factors, all upregulated in mPB-derived erythroid
      progenitors, coupled to common upregulated NUDC gene involved in the
      proliferation of erythroid cells. CONCLUSION: This report provides an extensive
      transcriptional profile of cultured erythroid progenitors and leads to a better
      understanding of diversity among the progenitor sources.

PMID- 24659681
TI  - Bradycardia during induction therapy with all-trans retinoic acid (ATRA).

PMID- 24659682
TI  - Successful treatment of myeloid sarcoma with local treatment modalities: the
      longest overall survival in published literature.

PMID- 24659683
TI  - Squamous cell carcinoma developed on Kyrle's disease scar.

PMID- 24659684
TI  - Are there new possibilities for the use of positron emission tomography in
      oncology?

PMID- 24659685
TI  - The fascinating germ theories on cancer pathogenesis.
AB  - For more than 100 years, the germ theory of cancer, proposing that microorganisms
      were at the origin of the disease, dominated medicine. Several eminent scientists
      like Etienne Burnet, Mikhail Stepanovich Voronin, Charles-Louis Malassez, and
      Francis-Peyton Rous argued on the pathogenesis presenting their theories that
      implicated cocci, fungi and parasites. The impact of these theories was
      culminated by the Nobel Prize in 1926 that was attributed to the Danish scientist
      Johannes Fibiger for his work on the nematode Spiroptera as a causative agent in
      cancer. Even if those theories were the result of fantasy and misinterpretation,
      they paved the way for the scientific research in oncology. 

PMID- 24659686
TI  - COX-2 overexpression increases malignant potential of human glioma cells through
      Id1.
AB  - Increased COX-2 expression directly correlates with glioma grade and is
      associated with shorter survival in glioblastoma (GBM) patients. COX-2 is also
      regulated by epidermal growth factor receptor signaling which is important in the
      pathogenesis of GBMs. However, COX-2 expression has not been previously shown to
      directly alter malignancy of GBMs. Id1 is a member of the helix-loop-helix (HLH)
      family of transcriptional repressors that act as dominant-negative inhibitors of
      basic-HLH factors. This factor has been shown to be regulated by COX-2 in breast
      carcinoma cells and recent studies suggest that Id1 may also be involved in the
      genesis/progression of gliomas. We now show that COX-2 increases the
      aggressiveness of GBM cells. GBM cells with COX-2 overexpression show increased
      growth of colonies in soft agar. Tumorigenesis in vivo is also increased in both
      subcutaneous flank and orthotopic intracranial tumor models. COX-2 overexpression
      induces Id1 expression in two GBM cell lines suggesting a role for Id1 in glioma
      transformation/tumorigenesis. Furthermore, we find direct evidence of a role for
      Id1 with significant suppression of in vitro transformation and in vivo
      tumorigenesis in COX-2-overexpressing GBM cells where Id1 has been knocked down.
      In fact, Id1 is even more efficient at enhancing transformation/tumorigenesis of
      GBM cells than COX-2. Finally, GBM cells with COX-2 or Id1 overexpression show
      greater migration/invasive potential and tumors that arise from these cells also
      display increased microvessel density, results in line with the increased
      malignant potential seen in these cells. Thus, COX-2 enhances the malignancy of
      GBM cells through induction of Id1. 

PMID- 24659687
TI  - Integrin alpha4beta1 is necessary for CD4+ T cell-mediated protection against
      genital Chlamydia trachomatis infection.
AB  - Chlamydia trachomatis infection is the most common sexually transmitted bacterial
      infection in the United States and a significant health burden worldwide.
      Protection from Chlamydia infection in the genital mucosa is dependent on IFN
      gamma derived from CD4(+) Th1 cells. These CD4(+) T cells must home successfully
      to the genital tract to exert their effector function and decrease C. trachomatis
      burden. Although adhesion receptors expressed by CD4(+) T cells in the genital
      tract have been characterized, the integrin receptor required for Chlamydia
      specific CD4(+) T cell-mediated protection has not been explored. In this study,
      we demonstrate that C. trachomatis infection of the upper genital tract results
      in recruitment of Chlamydia-specific CD4(+) T cells robustly expressing the
      integrin alpha4beta1. Interfering with alpha4beta1, but not alpha4beta7, function
      resulted in defective CD4(+) T cell trafficking to the uterus and high bacterial
      load. We conclude that integrin alpha4beta1 is necessary for CD4(+) T cell
      mediated protection against C. trachomatis infection in the genital mucosa. By
      identifying homing molecules required for successful CD4(+) T cell trafficking to
      C. trachomatis-infected tissues, we will be better equipped to design vaccines
      that elicit sterilizing, long-lasting immunity without inducing immune
      pathologies in the upper genital tract. 

PMID- 24659688
TI  - TLR4 ligands lipopolysaccharide and monophosphoryl lipid a differentially
      regulate effector and memory CD8+ T Cell differentiation.
AB  - Vaccines formulated with nonreplicating pathogens require adjuvants to help
      bolster immunogenicity. The role of adjuvants in Ab production has been well
      studied, but how they influence memory CD8(+) T cell differentiation remains
      poorly defined. In this study we implemented dendritic cell-mediated immunization
      to study the effects of commonly used adjuvants, TLR ligands, on effector and
      memory CD8(+) T cell differentiation in mice. Intriguingly, we found that the
      TLR4 ligand LPS was far more superior to other TLR ligands in generating memory
      CD8(+) T cells upon immunization. LPS boosted clonal expansion similar to the
      other adjuvants, but fewer of the activated CD8(+) T cells died during
      contraction, generating a larger pool of memory cells. Surprisingly,
      monophosphoryl lipid A (MPLA), another TLR4 ligand, enhanced clonal expansion of
      effector CD8(+) T cells, but it also promoted their terminal differentiation and
      contraction; thus, fewer memory CD8(+) T cells formed, and MPLA-primed animals
      were less protected against secondary infection compared with those primed with
      LPS. Furthermore, gene expression profiling revealed that LPS-primed effector
      cells displayed a stronger pro-memory gene expression signature, whereas the gene
      expression profile of MPLA-primed effector cells aligned closer with terminal
      effector CD8(+) T cells. Lastly, we demonstrated that the LPS-TLR4-derived "pro
      memory" signals were MyD88, but not Toll/IL-1R domain-containing adapter inducing
      IFN-beta, dependent. This study reveals the influential power of adjuvants on the
      quantity and quality of CD8(+) T cell memory, and that attention to adjuvant
      selection is crucial because boosting effector cell expansion may not always
      equate with more memory T cells or greater protection. 

PMID- 24659689
TI  - Mycobacterium tuberculosis impairs dendritic cell functions through the serine
      hydrolase Hip1.
AB  - Mycobacterium tuberculosis is a highly successful human pathogen that primarily
      resides in host phagocytes, such as macrophages and dendritic cells (DCs), and
      interferes with their functions. Although multiple strategies used by M.
      tuberculosis to modulate macrophage responses have been discovered, interactions
      between M. tuberculosis and DCs are less well understood. DCs are the primary
      APCs of the immune system and play a central role in linking innate and adaptive
      immune responses to microbial pathogens. In this study, we show that M.
      tuberculosis impairs DC cytokine secretion, maturation, and Ag presentation
      through the cell envelope-associated serine hydrolase, Hip1. Compared to wild
      type, a hip1 mutant strain of M. tuberculosis induced enhanced levels of the key
      Th1-inducing cytokine IL-12, as well as other proinflammatory cytokines (IL-23,
      IL-6, TNF-alpha, IL-1beta, and IL-18) in DCs via MyD88- and TLR2/9-dependent
      pathways, indicating that Hip1 restricts optimal DC inflammatory responses.
      Infection with the hip1 mutant also induced higher levels of MHC class II and
      costimulatory molecules CD40 and CD86, indicating that M. tuberculosis impairs DC
      maturation through Hip1. Further, we show that M. tuberculosis promotes
      suboptimal Ag presentation, as DCs infected with the hip1 mutant showed increased
      capacity to present Ag to OT-II- and early secreted antigenic target 6-specific
      transgenic CD4 T cells and enhanced Th1 and Th17 polarization. Overall, these
      data show that M. tuberculosis impairs DC functions and modulates the nature of
      Ag-specific T cell responses, with important implications for vaccination
      strategies. 

PMID- 24659690
TI  - Multiple CD11c+ cells collaboratively express IL-1beta to modulate stromal
      vascular endothelial growth factor and lymph node vascular-stromal growth.
AB  - Lymphadenopathy in autoimmune and other lymphoproliferative diseases is in part
      characterized by immunoblasts and vascular proliferation. The lymph node
      vasculature, along with the nonvascular stromal compartment, supports lymphocyte
      function, and targeting vascular-stromal expansion in inflamed nodes may modulate
      lymphocyte function in disease. CD11c(+) cells are essential for vascular-stromal
      proliferation and the upregulation of vascular endothelial growth factor (VEGF)
      needed for vascular proliferation. However, targetable CD11c(+) cell-derived
      molecular mediators, the identity of relevant CD11c(+) cells, and whether
      CD11c(+) cells directly stimulate VEGF-expressing stromal cells are poorly
      understood. In this study we show that CD11c(+) CD11b(+) CCR2-dependent monocytes
      and CCR7-dependent dendritic cells express IL-1beta. IL-1beta blockade, IL-1beta
      deficiency in radiosensitive cells, and CCR2/CCR7 double deficiency but not
      single deficiency all attenuate immunization-induced vascular-stromal
      proliferation. gp38(+) stromal fibroblastic reticular cells (FRCs) that express
      VEGF are enriched for Thy1(+) cells and partially overlap with CCL21-expressing
      FRCs, and FRC VEGF is attenuated with IL-1beta deficiency or blockade. IL-1beta
      localizes to the outer borders of the T zone, where VEGF-expressing cells are
      also enriched. Ex vivo, CD11b(+) cells enriched for IL-1beta(+) cells can
      directly induce cultured gp38(+)Thy1(+) FRCs to upregulate VEGF. Taken together,
      these results suggest a mechanism whereby multiple recruited CD11c(+) populations
      express IL-1beta and directly modulate FRC function to help promote the
      initiation of vascular-stromal growth in stimulated lymph nodes. These data
      provide new insight into how CD11c(+) cells regulate the lymph node vascular
      stromal compartment, add to the evolving understanding of functional stromal
      subsets, and suggest a possible utility for IL-1beta blockade in preventing
      inflammatory lymph node growth. 

PMID- 24659692
TI  - [Seroprevalence of Toxoplasma gondii in sheep in Silopi district by using
      indirect fluorescent antibody test (IFAT)].
AB  - OBJECTIVE: In the present study, it was aimed to detect seropositivity of T.
      gondii in sheep raised in the Silopi district. METHODS: For this aim, blood
      samples were obtained from 100 female Hamdani sheep. The serum samples were
      examined using indirect fluorescent antibody (IFA) with respect of T. gondii
      specific antibody. RESULTS: Seropositivity was detected in 97 of sheep examined
      (97%). The seropositivity titers for the IFA test showed that 1:16 in 58 (59.7%),
      1:64 in 22 (22.6%), 1:128 in 16 (16.4%) and 1:256 in 1 (%1) of sheep were found
      as seropositive. Seropositivity was observed as 96% in aborted sheep.
      Seropositivity was detected as 96% and 100% in 2-4 and 5-10 year old sheep,
      respectively. The relationship between age and seropositivity rate was not found
      significant (p > 0.05). CONCLUSION: The seropositivity of T. gondii was higher in
      sheep grown in Silopi.

PMID- 24659691
TI  - Axl receptor blockade ameliorates pulmonary pathology resulting from primary
      viral infection and viral exacerbation of asthma.
AB  - Viruses use Tyro3, Axl, and Mertk (TAM) receptor tyrosine kinases to infect and
      modulate the immune properties of various cell types, which led us to investigate
      whether TAM receptor activation affected primary viral infection and viral
      exacerbation of asthma in experimental models. In these lung-specific models, we
      observed that Axl was the most abundantly induced TAM receptor protein. During
      primary respiratory syncytial virus (RSV) infection, anti-Axl mAb treatment
      significantly increased the number of IFN-gamma-producing T cells and NK cells
      and significantly suppressed RSV replication and whole lung levels of IL-4 and IL
      13. Intrapulmonary H1N1 infection induced lethal pulmonary inflammation, but anti
      Axl mAb treatment of infected mice significantly increased the number of IFN-beta
      producing macrophages and dendritic cells and significantly suppressed neutrophil
      infiltration. Consequently, the lethal effect of H1N1 infection in this model was
      significantly reduced in the mAb-treated group compared with the IgG control
      treated group. Targeting Axl also inhibited airway hyperresponsiveness, IL-4 and
      IL-13 production, and goblet cell metaplasia in an Aspergillus fumigatus-induced
      asthma model. Finally, infection of mice with RSV during fungal asthma
      significantly exacerbated airway inflammation, goblet cell metaplasia, and airway
      remodeling, but all of these features in this viral exacerbation model were
      ameliorated by anti-Axl mAb treatment. Taken together, these results demonstrate
      that Axl modulates the pulmonary immune response during viral and/or allergic
      pathology, and they also suggest that targeting this TAM receptor might provide a
      novel therapeutic approach in these infectious diseases. 

PMID- 24659693
TI  - The current status of cutaneous leishmaniasis in Morocco.
AB  - Cutaneous leishmaniasis (CL) is a public health problem on a global level because
      it affects the population of 88 countries. In Morocco, it is widely distributed,
      caused by Leishmania tropica, Leishmania major and Leishmania infantum rarely.
      The geographical distribution of different forms of leishmaniasis in Morocco is
      linked to well described bioclimatic zones. Over the past two decades, the
      epidemiological situation of CL has changed significantly. It acquire an
      increasingly epidemic status with geographic expansion to previously free areas
      and the emergence of overlapping foci of cutaneous leishmaniasis and visceral
      leishmaniasis in several provinces of Morocco. In this review the evolution of
      the epidemiological situation and epidemiological factors which influenced the
      course of it in the past two decades will be reported.

PMID- 24659694
TI  - [The prevalence of Demodex sp. in patients admitted to the parasitology
      laboratory of the Dursun Odabas Medical Center in Yuzuncu Yil University, Van].
AB  - OBJECTIVE: The aim of the study was to determine the prevalence of Demodex sp. in
      patients referred fom the Dermatology Outpatient Clinic to the Parasitology
      Laboratory, Dursun Odabas Medical Center of the Yuzuncu Yil University. METHODS:
      The study was conducted between May 2012-May 2013. The samples were taken from 67
      patients using the standard skin surface biopsy method. RESULTS: Demodex sp.
      mites were identified in 47.4% of 38 women, and in 48.3% of 29 male patients.
      These mites were detected in 15.8% of 19 patients who were 35 years old and
      younger, and in 60.4% of 48 patients who were 36 years old and older. Overall,
      47.8% (32 patients) of 67 patients were found positive for demodicosis. It was
      determined that 53.1% of Demodex sp. positive patients had eritemato
      telangiectatic rosacea, 21.9% had papulo-pustular type rosacea, 18.8% had
      papules, 3.1% had erythematous pustules, and 3.1% had erythematous squamous
      plaques. There was a statistically significant difference between the Demodex sp.
      positivity and age groups (p=0.001). CONCLUSION: It was concluded that
      dermatologists should also take into consideration the possible presence of
      Demodex sp. mites in patients with skin symptoms such as erythema,
      telangiectasia, papules and pustules, and apply the appropriate treatment for
      these parasites.

PMID- 24659695
TI  - Parasitic infections of the appendix as a cause of appendectomy in adult
      patients.
AB  - OBJECTIVE: Assessment of frequency and clinical findings of parasitic infections
      for etiology of acute appendicitis. METHODS: Data of 1452 patients who were
      carried out appendectomy between January 1999 and December 2012 were analyzed
      retrospectively. Appendectomy was performed in 1159 of the patients with a pre
      diagnosis of acute appendicitis. Demographics, physical findings, radiologic and
      laboratory studies, operative findings, pathological results, presence and type
      of parasitosis were investigated. RESULTS: Among the 1159 patients done
      appendectomy with a pre diagnosis of acute appendicitis, 719 (62%) were males and
      440 (38%) were females. Parasitic infection was demonstrated in 17 (1.4%) of
      them. Mean average age of these patients was 36.6 +/- 20.1 years. Enterobius
      vermicularis was present in 15 (88.2%) and Entamoeba histolytica in 2 (11.8%) of
      the patients. Of the pathology specimens of appendix consisting Enterobius
      vermicularis, 12 (80%) were normal appendix tissues, 1 (6.6%) was acute
      uncomplicated appendicitis and 2 (13.3%) were perforated appendicitis. One (50%)
      of the two specimens consisting Entamoeba histolytica was normal appendix and the
      other (50%) was acute appendicitis. CONCLUSION: Differential diagnosis of
      parasitic infections in etiology of acute appendicitis should be made properly.
      It must be remembered that this attention can save patients from a negative
      laparotomy and morbidity and mortality of it.

PMID- 24659696
TI  - [Helminths identified by coprological examination in cattle raised in Bartin
      region].
AB  - OBJECTIVE: This study was carried out to detect the presence and prevalence of
      helminths in cattle between March 2011-June 2012 in the Bartin and Amasra
      districts. METHODS: A total of 141 feacal samples of cattle younger than 1 year
      old (n=12), between 1 and 3 years old (n=48), more than 3 years old (n=81) were
      analyzed with sedimentation, flotation and Baermann Wetzel methods. Strongylid
      eggs in feaces were cultured and the larvae were then collected and identified.
      RESULTS: Of 141 cattle examined, 104 (73.75%) were obseved to be infected with
      various helminths. The ratio of infection was 66.67% in the under 1 year old,
      93.75% in 1-3 year old and 62.96% in over 3 year old cattle and 73.68% in female
      and 74.07% male. 68.4% of Holstein, 91.67% of Simental and 75% of domestic cattle
      were found to be infected with various helminths. CONCLUSION: The helminth
      infection of cattle in the Bartin province is a problem that should not be
      ignored. Breeders should informed about this subject and necessary measures
      should be taken.

PMID- 24659697
TI  - Prevalence of Cryptosporidium infection in sheep in Iran.
AB  - OBJECTIVE: Cryptosporidium is an important zoonotic parasite in humans and
      animals worldwide. This study was conducted to investigate the prevalence of
      Cryptosporidium infection in Iran. METHODS: Fecal samples (n=1.749) were
      collected randomly in asymptomatic sheep from different rural regions of Iran in
      2011 to 2012. All samples were examined by using the cold modified Ziehl-Neelsen
      staining technique. RESULTS: Oocysts of Cryptosporidium was found in 11.3%
      (198/1749) of samples (9.8 < CI 95% < 12.8). There was a statistical differences
      among Cryptosporidium infection, age groups (p < 0.0001), and gender (p=0.02).
      CONCLUSION: This study is the first report of Cryptosporidium infection in sheep
      in different regions of Iran. Therefore, further comprehensive molecular studies
      in sheep to identify the source of contaminations (animals or humans) and
      designing control strategies is highly recommended.

PMID- 24659698
TI  - Partial purification and properties of adenosine triphosphatase (ATPase) from
      liver fluke Fasciola hepatica.
AB  - OBJECTIVE: The adenosine triphosphatase (ATP phosphohydrolase, EC
      3.6.1.3.;ATPase) is a membrane -bound enzyme which transport protons across the
      plasma membrane using ATP as an energy source. METHODS: The adenosine
      triphosphatase (ATPase ; EC: 3.6.1.3) was extracted from membrane preparations of
      adult Fasciola hepatica by chloroform treatment and purified by means of ammonium
      sulphate fractionation, gel filtration on sephadex G-200 and DEAE- Cellulose
      chromatography. RESULTS: The molecular weight was calculated to be 305.000 dalton
      by gel filtration. Kinetic experiments demonstrated a biphasic linear lineweaver 
      burk relationship (km=0.142 and 1.66 mM) thus revealing the existence of two
      substrate binding enzyme sites. CONCLUSION: In our study revealed that partial
      inhibition of Mg2+ dependent purified enzyme by oligomycin suggest the absence of
      mitochondrial ATPase in F. hepatica.

PMID- 24659699
TI  - Prevalence of head lice in two socio-economically different schools in the center
      of Izmir City, Turkey.
AB  - OBJECTIVE: The well-known and common infestation caused by Pediculus humanus
      capitis is an important public health and a social issue in many communities in
      the world. The aim of this study was to compare the head louse infestation rate
      in two schools having pupils from different socio-economic levels in the city
      center of Izmir. METHODS: The pupils aged between 6 and 11 years, were screened
      for the presence of eggs and nymph/adult lice using a fine-tooth head louse comb.
      RESULTS: A total of 88 and 126 pupils from the schools with low and medium socio
      economic level were screened and 24 (27.2%) and 5 (3.96%) of them were found to
      be positive for head lice, respectively. Overall, the infestation rate among
      girls was 3.14 times higher than in boys. CONCLUSION: Head louse infestation is a
      significant public health problem among primary schools. Increasing the knowledge
      about pediculosis and self-hygiene would be helpful in successfully reducing head
      louse infestation in the school setting. School authorities must encourage the
      parents to look for head lice routinely and a "school nurse" system is needed for
      effective head louse control in the schools.

PMID- 24659700
TI  - [The prevalence of Dicrocoeliid (Trematoda: Digenea) larval stages in Helix
      lucorum Linneus 1758 (Mollusca: Pulmonata) in the vicinity of Kastamonu].
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of
      Dicrocoeliid larval stages in Helix lucorum Linnaeus, 1758 (Mollusca: Pulmonata)
      living in the vicinity of Kastamonu. METHODS: Snails were collected in the
      vicinity of Taskopru, Kastamonu in March, April, May 2013. They were dissected
      while alive and their hepatopankreas were removed and placed on clean glass slide
      with a drop of 0.6% NaCl solution. The hepatopankreas were incised with a mounted
      needle and a thin film of the hepatopankreas fluid was drown out on a slide for
      examination of live parasites. After examination, larval stages fixed in %70
      alcohol, formaldehyde-ethyl alcohol, 10% formalin and bouin. RESULTS: H. lucorum
      which is a land snail species has been reported for the first time being an
      intermediate host in the life cycle of Dicrocoeliid (Trematoda: Digenea) species
      with the prevalence of 27.6% from our country. Morphological and histological
      features of larval stages were determined. CONCLUSION: H. lucorum is an
      intermediate host in the life cycle of Dicrocoeliid species. The prevalence of
      infection was highest in April. This land snail species is important for the
      health of animal and human.

PMID- 24659701
TI  - [Cysticercus bovis in Turkey and its importance from the public health aspect].
AB  - This study was conducted in order to compare the different regions according to
      the literature on the prevalence of bovine cysticercosis and T. saginata in
      Turkey. Bovine cysticercosis and T. saginata status were evaluated
      retrospectively. The distribution of the data obtained according to provinces and
      regions were showed in the Table and the minumum / maximum values of this data in
      different regions in the Figure. The data obtained through the literature showed
      that the prevalence of C. bovis and T. saginata infections are parallel in the
      same region. The higher prevalence of both C. bovis and T. saginata infections
      was determined in the Southeastern Anatolia, Eastern Anatolia and Central
      Anatolia regions respectively.

PMID- 24659703
TI  - [Isolated gluteal hydatid cyst].
AB  - Hydatid cyst disease is a parasitic infection caused by Echinococcus granulosus
      and poses a serious health problem in endemic areas, including our country.
      Hydatid disease mostly affects the liver and lung, although involvements in many
      parts of the body have been reported in the literature. Isolated soft tissue
      involvement is very rare. We present an isolated hydatid disease case which
      affected the gluteal region of the body.

PMID- 24659702
TI  - [Amblyomma spp. case related to overseas travel].
AB  - Ticks are a threat to human health by blood sucking and vectoring many disease
      agents. Tick-borne diseases are seen all over the world and play an important
      role in the dissemination of diseases. Although many of the tick species are
      present in Turkey, Amblyomma genus is seen more in South America and Africa. In
      this case,a person returning to the country after travelling to Africa who
      presented to the hospital complaining of tick bites and brought ticks to the
      parasitology laboratory was identified as Ablyomma spp. nymph. This case is a
      report concerning care of tick bites when travelling abroad and shows that these
      ticks can transmit disease agents from abroad.

PMID- 24659704
TI  - [Left lumbar subcutenous hydatid cyst disease: a case report].
AB  - Hydatid cyst disease is endemic in our country. This disease is most commonly
      detected in the liver and lung, but it can be detected rarely in the soft tissue,
      muscles and subdermally. In this study, we mentioned a case with subcutaneous
      hydatid cyst disease without any primary lesion. In this case, a left lumbar
      subdermal cyst was totally excised and the germinative membrane of the cyst was
      detected and sent for pathological examination and study resultsreported hydatid
      cyst disease. The patient was followed up for one year with laboratory and
      radiological studies. No recurrent hydatid cyst was observed. Turkey is an
      endemic area for hydatid cyst disease and we should bear this disease in mind as
      a differential diagnosis in all cystic lesions.

PMID- 24659705
TI  - [Acute appendicitis and coinfection with enterobiasis and taeniasis: a case
      report].
AB  - Parasites are rarely associated with inflammation of the appendix. Generally,
      parasites cause acute abdominal pain via blocking the gut lumen. In this article,
      we presented a case of appendicitis where Enterobius vermicularis was detected in
      the surgical specimen and Taenia was detected in the stool. A 31 year old male
      patient was admitted to the emergency room with severe abdominal pain, which has
      begun two days ago. On physical examination, tenderness was positive on palpation
      of the right lower abdominal quadrant and the patient was operated on with the
      diagnosis of acute appendicitis. Histopathological examination of the patient's
      appendectomy material revealed numerous parts of parasites resembling Enterobius
      vermicularis and slight mucosal erosion. On parasitological examination of the
      patient's stool, Taenia eggs and adult forms were determined. Antiparasitic
      therapy was started with niclosamide for taeniasis and albendazole for
      enterobiasis. Parasitic infections can mimic acute appendicitis clinically.
      Radiological and laboratory findings do not help to distinguish the diagnosis of
      acute appendicitis. In the histopathological examination of the appendix, the
      findings of acute inflammation of the appendix wall may not be defined. For
      patients with normal histopathological examination, screening for parasites
      should be done, and anti-parasitic treatment should be started after
      appendectomy.

PMID- 24659706
TI  - [The management of therapeutic failure in a falciparum malaria patient under oral
      arthemether-lumefantrine therapy].
AB  - Malaria is a parasitic infection characterized by anemia, splenomegaly and
      periodic fever. This infection has a tendency to cause serious complications.
      Falciparum malaria could occur in our country as an imported case due to
      increasing intercontinental travel opportunities. The World Health Organisation
      (WHO) recommends arthemether combination treatment as a first line choice. Here
      we report a Turkish case admitted to the hospital with high fever, sweating and
      fatigue. He had been in Uganda for 6 months without prophylaxis. Plasmodium
      falciparum with an intense parasitic load was diagnosed. We started arthemether
      lumefantrine combination therapy immediately. 18 days after his discharge he was
      readmitted with the same complaints and parasitemia was detected once again. This
      time, we treated him with the quinine-tetracycline combination regime for 7 days.
      Within 48 hours the patient was afebrile and the blood smear was negative.
      Falciparum malaria must be considered in infection emergencies for febrile
      patients especially with any travel history. For an initial therapy,
      arthemetherlumefantrine combination is a successful choice of treatment. Even
      with adequate treatment of arthemether-lumefantrine combination, the problems of
      recurrence (recrudescence or reinfection) could occur due to treatment failure.
      For the possibility of recurrence, close monitoring of patients is very important
      in the critical course after adequate treatment.

PMID- 24659707
TI  - [Primary retroperitoneal hydatid cyst].
AB  - Hydatid cysts cause diseases most frequently by localizing in the liver and the
      lungs. Hydatid cysts with retroperitoneal localization are very rare. A 45-year
      old female patient presented to our hospital with complaints of back pain, weight
      loss, and fatigue. The computerized tomography (CT) revealed that the patient had
      a septated cystic lesion of about 8x7x6 cm localized in the posterior of the left
      kidney, in the paravertebral site causing destruction of the neighboring costa.
      During laparotomy, the wall of the cyst with retroperitoneal localization was
      partially excised and the remaining cavity was drained. The drain was removed on
      post-op day 5. The histopathological diagnosis was reported to be a hydatid cyst.
      No problems were seen during the follow-ups of the patient who was administered
      post-op albendazole. Hydatid cysts are an endemic disease in our country and it
      should be kept in mind that they also have atypical localizations.

PMID- 24659708
TI  - A case of auricular, anal and umbilical myiasis caused by the larvae of Phormia
      regina (Meigen) (Diptera: Calliphoridae) in neonatal kittens.
AB  - The occurrence of feline myiasis is rare. Massive infestations of dipteran larvae
      can lead to death if not treated at an early stage. Auricular, anal and umbilical
      myiasis was detected in three neonatal kittens. The dipteran larvae were
      collected, fixed in 70% alcohol and clarified with 10% KOH for a few days. Later,
      larvae were dissected under the stereomicroscope, mounted on slides and then
      identified as the third instar of the black blowfly, Phormia regina (Meigen)
      (Diptera: Calliphoridae), according to their stigmatic and cephaloskeleton
      structures. Original measurements and figures are presented. Treatment included
      mechanical removal of larvae and cleansing of the area by applying
      polyvinylpyrrolidone-iodine complex. The presence of P. regina in cats has been
      reported here for the first time in Turkey.

PMID- 24659710
TI  - Serological and shedding patterns after Coxiella burnetii vaccination in the
      third gestation trimester in dairy cows.
AB  - This study sought to assess the effects of an inactivated phase I vaccine against
      Coxiella burnetii at the start of the third trimester of gestation on serological
      profiles, bacterial shedding patterns and subsequent reproductive performance in
      dairy cows. Cows were randomly assigned to a control (n = 78) or a vaccinated (n
      = 78) group on days 171-177 of gestation. Samples of placenta and colostrums at
      parturition, vaginal fluid, faeces, milk (PCR identification) and blood (anti-C.
      burnetii antibody detection) were obtained on the day of treatment and on days 91
      97 post partum, and also on parturition day and weekly on days 1-7, 8-14, 15-21,
      22-28 and 29-35 post partum in a subset of 70 animals. By Kaplan-Meier survival
      analysis, no significant effect of vaccination was detected on any of the
      reproductive variables studied. According to the odds ratio, C. burnetii shedding
      on days 171-177 of gestation was highly correlated with seropositivity against C.
      burnetii (OR = 9.1), while vaccination was not linked to reduced shedding of the
      bacterium. In shedders compared to others, the likelihood of pregnancy to first
      AI decreased and increased by factors of 0.26 and 16.1 on days 1-35 and 91-97
      post partum, respectively. In conclusion, when administered at the start of the
      third trimester of pregnancy, the inactivated C. burnetii phase I vaccine failed
      to reduce bacterial shedding. 

PMID- 24659711
TI  - Occurrence and genetic diversity of pigeon circovirus strains in Poland.
AB  - Pigeon circovirus (PiCV) is an immunosuppressive agent widespread throughout the
      world, which causes a disease in pigeons called Young Pigeon Disease Syndrome.
      The aim of the study was to evaluate the prevalence of PiCV in Poland and
      investigate the genetic diversity relative to other known PiCV isolates. Samples
      from 152 pigeon flocks (88 flocks of racing pigeons and 64 flocks of fancy
      pigeons) from various regions of Poland were tested by polymerase chain reaction
      and an approximately 326-base fragment of the capsid protein gene (Cap gene) of
      the virus was amplified. The average viral prevalence was found to be 70.3%
      (76.13% in racing pigeons and 62.5% in fancy pigeons). Among the obtained
      positive samples, 21 were selected for sequencing and a phylogenetic analysis was
      performed. It was found that the majority of Polish PiCV isolates, to varying
      degrees, are related to isolates occurring in Europe. It was also observed that
      the Cap gene is variable and mutations often occur in it, which impacts the amino
      acid sequences in the capsid protein (nucleotide similarity averaged 86.57%,
      amino acid similarity averaged 89.02%). 

PMID- 24659709
TI  - Epigenetic silencing of microRNA-199b-5p is associated with acquired
      chemoresistance via activation of JAG1-Notch1 signaling in ovarian cancer.
AB  - Epithelial ovarian cancer is a highly lethal and aggressive gynecological
      malignancy. The high mortality rate is due in part to the fact that many advanced
      cancer patients become refractory to current chemotherapeutic agents, leading to
      tumor recurrence and death. However, the underlying mechanisms leading to
      chemoresistance remain obscure. Here, we report that the loss of miR-199b-5p due
      to progressive epigenetic silencing leads to the activation of the JAG1-mediated
      Notch1 signaling cascade, thereby leading to the development of acquired
      chemoresistance in ovarian cancer. Using miRCURY LNATM microRNA array and Q-PCR
      analyses of two pairs of cisplatin-sensitive and -resistant ovarian cancer cell
      lines, we identified miR-199b-5p as significantly down-regulated in cisplatin
      resistant ovarian cancer cells and confirmed that miR-199b-5p is clinically
      associated with advanced and poor survival ovarian cancers. Interestingly, the
      loss of miR-199b-5p could be restored by 5-Aza-dC-mediated demethylation, and
      methylated specific PCR (MS-PCR), bisulfite-sequencing and pyrosequencing
      revealed that the promoter region of miR-199b-5p was hypermethylated.
      Computational and mechanistic analyses identified JAG1 as a primary target of miR
      199b-5p. Notably, the reduced expression of miR-199b-5p was found to be inversely
      correlated with the increased expression of JAG1 using an ovarian cancer tissue
      array. Enforced expression of miR-199b-5p sensitized ovarian cancer cells to
      cisplatin-induced cytotoxicity both in vitro and in vivo. Conversely, re
      expression of miR-199b-5p and siRNA-mediated JAG1 knockdown or treatment with
      Notch specific inhibitor gamma-secretase (GSI) attenuated JAG1-Notch1 signaling
      activity, thereby enhancing cisplatin-mediated cell cytotoxicity. Taken together,
      our study suggests that the epigenetic silencing of miR-199b-5p during tumor
      progression is significantly associated with acquired chemoresistance in ovarian
      cancer through the activation of JAG1-Notch1 signaling.

PMID- 24659712
TI  - Simultaneous detection of vaccinal and field infectious bursal disease viruses in
      layer chickens challenged with a very virulent strain after vaccination.
AB  - Infectious bursal disease virus is an important poultry pathogen. It is
      distributed worldwide and causes significant economic losses. In this study, a
      system was adopted for the simultaneous monitoring of vaccine and virulent
      strains using reverse transcription polymerase chain reaction (RT-PCR). After the
      decay of maternal antibodies, chickens were vaccinated at the age of 37 days with
      a virus of intermediate virulence and challenged at 5, 10 and 14 days post
      vaccination (dpv). The challenge was done with IBDV strain CH/99. Sequencing of
      the hypervariable region of VP2 has shown that CH/99 belongs to the very virulent
      group of viruses. The vaccine virus could be found in the bursa of Fabricius,
      spleen, thymus and bone marrow until 24 dpv. The CH/99 challenge virus was found
      in the bursa and lymphoid organs when chickens were challenged at 5 and 10 dpv.
      When challenge was performed at 14 dpv, the pathogenic virus could not be found
      in the bursa and other lymphoid organs. 

PMID- 24659713
TI  - Elevated Vascular Endothelial Growth Factor (VEGF) levels in the blood serum of
      dogs with malignant neoplasms of the oral cavity.
AB  - Angiogenesis plays an essential role in the development of a neoplastic tumour by
      conditioning both its growth and the formation of metastases. The induction of
      blood vessel growth occurs under the influence of proangiogenic factors, among
      which Vascular Endothelial Growth Factor (VEGF) seems to be the most important.
      The aim of this research was to study the level of VEGF measured by ELISA in the
      serum of dogs with neoplasms of the oral cavity. The study material comprised
      samples of neoplastic tissue from 17 operated dogs and the serum of the examined
      animals as well as of dogs from the control group. The tissue samples were taken
      from dogs of different breeds, aged 6-14 years. The tumour type was determined in
      accordance with the applicable WHO classification. Blood samples taken from sick
      dogs and from animals of the control group were centrifuged, and immunoenzymatic
      labelling of VEGF was performed in the obtained serum using ELISA and R&D system
      reagents (Quantikine Canine VEGF). All stages of VEGF labelling were performed
      according to the recommendation of the test manufacturer. The median of VEGF in
      the serum of the dogs with neoplasms of the oral cavity was 40.64 pg/mL. The
      lowest value of 14.26 pg/mL was observed in the case of fibrosarcoma, and the
      highest value of 99.19 pg/mL in the case of squamous cell carcinoma. The VEGF
      median in the control group amounted to 11.14 pg/mL whereas the VEGF value in the
      groups of animals diagnosed with benign tumours ranged between 2.30 and 19.74
      pg/mL. Elevated VEGF in the blood serum, in comparison with the benign tumour
      group and the control group, was observed in all examined neoplasms of the oral
      cavity. It was suggested that overexpression of VEGF can have a prognostic value
      and is useful in the early detection of neoplasms. 

PMID- 24659714
TI  - Expression of multidrug resistance membrane transporter (Pgp) and p53 protein in
      canine mammary tumours.
AB  - The aim of this study was to determine the expression rate of P-glycoprotein
      (Pgp), a multidrug resistance marker and the p53 tumour-suppressor protein in
      canine mammary tumours. A total of 30 tumours were examined in parallel to
      patient history. The tumours were allotted to four groups: tubulopapillar
      carcinomas, complex carcinomas, benign tumours, and other malignant tumours. A
      monoclonal mouse antibody (C494) was used for the immunohistochemical evaluation
      of Pgp and a polyclonal rabbit antibody for p53. We found that the intact ductal
      epithelium and connective tissue showed pronounced Pgp expression. The most
      intensive staining was detected in tubulopapillar carcinomas for both Pgp and
      p53. The expression rate of Pgp and p53 differed significantly between
      tubulopapillar carcinoma and complex carcinoma, and between tubulopapillar
      carcinoma and benign mammary tumour, respectively. The expressions of Pgp and p53
      highly correlated statistically; therefore, both can determine malignancy in a
      similar manner. In the case of tubulopapillar carcinomas, more relapsed tumours
      occurred than in relation to complex carcinomas and other malignant tumours. Pgp
      expression rate was proportional to the probability of the tumour becoming
      recidivant postoperatively, as well. These results suggest that routine
      evaluation of Pgp expression in canine mammary tumours may be prognostically
      helpful. 

PMID- 24659715
TI  - The B subunits of cholera and Escherichia coli heat-labile toxins enhance the
      immune responses in mice orally immunised with a recombinant live P-fimbrial
      vaccine for avian pathogenic E. coli.
AB  - This study aimed to investigate the adjuvant effect of recombinant attenuated
      Salmonella expressing cholera toxin B subunit (CTB) and Escherichia coli heat
      labile enterotoxin B subunit (LTB) for the P-fimbriae subunit-based vaccine of
      avian pathogenic E. coli (APEC) in a murine model. The PapA-specific sIgA and IgG
      responses were significantly enhanced after immunisation with the Salmonella-PapA
      vaccine in the presence of CTB or LTB. The group immunised with the Salmonella
      LTB strain promoted Th1-type immunity, whereas that immunised with the Salmonella
      CTB strain produced Th2-type immunity. We concluded that both Salmonella-CTB and 
      LTB strains can enhance the immune response to PapA, and that the LTB strain may
      be a more effective adjuvant for APEC vaccination, which requires higher Th1-type
      immunity for protection. Thus, our findings provide evidence that immunisation
      with an adjuvant, LTB, is one of the strategies of developing effective vaccines
      against P-fimbriated APEC. 

PMID- 24659716
TI  - Expression of adiponectin receptors 1 and 2 in the ovary and concentration of
      plasma adiponectin during the oestrous cycle of the pig.
AB  - The aim of this study was to compare the expression levels of adiponectin
      receptor 1 and adiponectin receptor 2 mRNAs and proteins in porcine ovaries
      during four stages (days 2 to 3, 10 to 12, 14 to 16, 17 to 19) of the oestrous
      cycle and to measure adiponectin plasma concentrations during the same phases of
      the cycle. Higher mRNA expression of adiponectin receptor 1 was detected in
      porcine granulosa cells than in corpora lutea and theca cells (P < 0.01). In
      contrast, higher gene expression of adiponectin receptor 2 occurred in newly
      developed and mature corpora lutea (P < 0.01). The adiponectin receptor 1 protein
      content was the highest in corpora lutea isolated on days 2 to 3 of the cycle and
      was the lowest in theca interna cells (P < 0.01). The profile of adiponectin
      receptor 2 protein was similar to that of adiponectin receptor 1. Adiponectin
      plasma concentrations were significantly higher throughout the luteal phase than
      in the follicular phase (P < 0.01). In conclusion, the presence of adiponectin
      receptor 1 and adiponectin receptor 2 mRNAs and proteins in the porcine ovary
      suggests that adiponectin may directly affect ovarian functions through its own
      specific receptors. The expression of both receptors and adiponectin plasma
      concentration were dependent on hormonal status related to the stage of the
      cycle. 

PMID- 24659717
TI  - Impact of butyl benzyl phthalate on development of the reproductive system of
      European pikeperch, Sander lucioperca (L.).
AB  - The effect of butyl benzyl phthalate (BBP) on the sex differentiation process of
      fish is practically unknown. The experimental material of this study was juvenile
      European pikeperch [Sander lucioperca (L.)], which is gonochoristic, undergoes
      immediate sex differentiation, and has a fixed gonad differentiation period. The
      fish were fed a diet supplemented with BBP (during the sex differentiation phase:
      age 61-96 days post hatch) in the following quantities: 1.0; 2.0; 4.0; 8.0; 16.0
      g BBP kg-1 feed. The control feed was a xenobiotic-free base feed. In the present
      experiment lasting 10 weeks, the survival and growth of fish, the
      histopathological changes of the fish gonads and the sex ratio were evaluated.
      After administration of the two highest doses of BBP, growth inhibition of the
      fish was observed. BBP also seriously disturbed the gonadal differentiation
      process of pikeperch. All analysed concentrations of BBP delayed testicular
      development and, at concentrations of 4.0, 8.0 and 16.0 g BBP kg-1, induction of
      the feminisation process was observed. The sex ratio was distinctly disrupted in
      groups receiving 8.0 and 16.0 g BBP kg-1. 

PMID- 24659718
TI  - Effects of steroids on the morphology and proliferation of canine and equine
      mesenchymal stem cells of adipose origin - in vitro research.
AB  - Disorders of the locomotive system, especially those occurring due to
      degenerative changes of the joints, are serious problems in daily veterinary
      medical practice. Steroid injections are the main way of treating these
      disorders. However, this approach brings usually only temporary effects of pain
      relief, and may cause many side effects. Alternative therapies focus on
      regeneration of damaged tissue using adult mesenchymal stem cells (MSCs). Since
      2002, the great plasticity and immunomodulatory properties of MSCs isolated from
      adipose tissue (AdMSCs) have been used successfully in the treatment of
      degenerative joint diseases (DJD) of both dogs and horses. Possible simultaneous
      application of steroid therapy and stem cell transplantation could improve the
      commonly used clinical procedure. In this paper, the influence of the two steroid
      drugs (betamethasone and methylprednisolone) on AdMSCs was evaluated on the basis
      of morphology and proliferation rate. Both steroids positively influenced the
      viability and proliferation state of cells in a concentration of 0.01 mg/ml and
      0.1 mg/ml, respectively. However, the concentration of 1 mg/ml had a cytotoxic
      effect. Moreover, the lower dosage of steroid drugs used in the experiment did
      not affect the morphology of cells and significantly increased cellular activity.
      In conclusion, our data demonstrate the stimulating effect of steroid drugs on
      cell morphology, proliferation rate and cytophysiological activity. These
      findings may influence the use of stem cells and steroids in applied regenerative
      veterinary medical practice in the future. 

PMID- 24659719
TI  - A potential therapeutic strategy for chronic lymphocytic leukemia by combining
      Idelalisib and GS-9973, a novel spleen tyrosine kinase (Syk) inhibitor.
AB  - Agents that target B-cell receptor (BCR) signaling in lymphoid malignancies
      including idelalisib (GS-1101) and fostamatinib which inhibit the delta isoform
      of PI3 kinase (PI3Kd) and spleen tyrosine kinase (Syk) respectively have shown
      significant clinical activity. By disrupting B-cell signaling pathways,
      idelalisib treatment has been associated with a dramatic lymph node response, but
      eradication of disease and relapse in high risk disease remain challenges.
      Targeting the BCR signaling pathway with simultaneous inhibition of PI3Kd and Syk
      has not yet been reported. We evaluated the pre-clinical activity of idelalisib
      combined with the novel and selective Syk inhibitor GS-9973 in primary peripheral
      blood and bone marrow Chronic Lymphocytic Leukemia (CLL) samples. Both PI3Kd and
      Syk inhibition reduced CLL survival and in combination induced synergistic growth
      inhibition and further disrupted chemokine signaling at nanomolar concentrations
      including in bone marrow derived and poor risk samples. Simultaneous targeting of
      these kinases may significantly increase clinical activity. 

PMID- 24659720
TI  - Short- and long-term outcome of dogs following surgical correction of a
      persistent right aortic arch.
AB  - This study reports the survival to discharge, postdischarge survival, and long
      term outcome of dogs following surgical correction of a persistent right aortic
      arch (PRAA). Information for 52 dogs, 28 dogs, and 23 dogs was available for
      analysis of survival to discharge, postdischarge survival, and long-term outcome,
      respectively. Ninety-two percent of dogs survived to the time of discharge and
      18% of dogs surviving to discharge were euthanized within 2 mo of surgery. Breed,
      age at the time of presentation, and gender were not correlated with increased
      odds of death prior to discharge from the hospital. Long-term outcome for dogs
      was excellent in 30%, good in 57%, and poor in 13% of dogs. Although this study
      shows a relatively high mortality rate prior to discharge from the hospital and
      within 2 mo of surgical treatment, the long-term outcome is good or excellent in
      87% of survivors. Dogs frequently display either residual clinical signs or
      require dietary modification long-term, but owner satisfaction is high. 

PMID- 24659721
TI  - Distal renal tubular acidosis associated with concurrent leptospirosis in a dog.
AB  - A 9 yr old spayed female boxer was presented for evaluation of vomiting,
      lethargy, anorexia, and weight loss. Initial laboratory evaluation revealed a
      hyperchloremic normal anion gap metabolic acidosis with alkaline urine that was
      consistent with a diagnosis of distal renal tubular acidosis (RTA). Targeted
      therapy was initiated with Na bicarbonate (HCO3) and potassium (K) gluconate.
      Leptospirosis was subsequently diagnosed with paired microagglutination testing
      (MAT), and doxycycline was added to the other treatments. Clinical signs
      resolved, and 6 mo after diagnosis, although the dog remained on alkali therapy
      (i.e., NaHCO3 and K gluconate) and a mild metabolic acidosis persisted, the dog
      remained otherwise healthy with a good quality of life. To the authors'
      knowledge, this is the first report to describe the concomitant association of
      those two disorders. Leptospirosis should be considered for any case of RTA in
      dogs. 

PMID- 24659722
TI  - Spontaneous resolution of postoperative chylothorax following surgery for
      persistent right aortic arch in two dogs.
AB  - Two young dogs underwent surgical management of a persistent right aortic arch
      (PRAA) and developed chylothorax postoperatively. In both cases, the surgical
      procedure and anesthetic recovery were uncomplicated and routine. Following
      surgery, both patients appeared bright, alert, responsive, and previous signs of
      regurgitation had resolved. Dyspnea and tachypnea developed 1-2 days
      postoperatively in each patient, and chylous effusion was detected on
      thoracocentesis. For each case, a diagnosis of chylothorax was based on cytology
      and triglyceride concentrations of the aspirated pleural fluid. Similar protocols
      for monitoring were used in the treatment of each patient's chylothorax. The
      duration and volume of chylous effusion production were closely monitored via
      routine thoracostomy tube aspiration. Both dogs rapidly progressed to recovery
      with no additional complications. With diligent monitoring, chylothorax secondary
      to surgical trauma can resolve in a rapid, uncomplicated manner. 

PMID- 24659723
TI  - Surgical excision of the parotid salivary gland for treatment of a traumatic
      mucocele in a dog.
AB  - A 3 yr old spayed female mixed-breed German shepherd dog was presented with a
      right facial swelling that developed after fighting with another dog. A parotid
      salivary mucocele was diagnosed via physical examination, fine-needle aspirate,
      and sialography of the parotid and mandibular salivary glands. Surgical excision
      of the right parotid salivary gland and duct was performed along with drainage of
      the mucocele. Neither intraoperative nor postoperative complications occurred,
      and follow-up examination 4 mo later revealed no evidence of recurrence. Case
      outcome was considered excellent. Sialography was useful for confirming the
      parotid gland as the source of the mucocele. Surgical excision of the parotid
      salivary gland is technically challenging, but an effective treatment option for
      traumatic mucoceles in the dog. 

PMID- 24659724
TI  - Recurrent gastric dilatation and intestinal dysmotility possibly resulting from
      autonomic neuropathy in a Great Dane.
AB  - A 5 yr old female spayed Great Dane was presented for recurrent episodes of
      gastric dilatation, intestinal dysmotility, and one episode of gastric rupture.
      Numerous hematologic, radiographic, and endocrine diagnostic tests were performed
      with no identifiable underlying cause. Many risk factors have been identified for
      gastric dilatation and most were present in this Great Dane. A number of
      symptomatic treatments, aimed primarily at altering the gastrointestinal tract
      flora and motility were tried, but failed to influence the clinical course of the
      disease. The dog continued to worsen, experienced more frequent episodes of
      gastric dilatation, and developed generalized muscle atrophy. Biopsies were
      collected from the biceps femoris and triceps brachii muscles. A pattern of
      denervation atrophy was evident in both muscles, consistent with polyneuropathy.
      The owners elected humane euthanasia and a necropsy was performed. A striking
      finding at necropsy was severe loss of myelinated fibers with extensive
      endoneurial fibrosis in the vagus nerve, consistent with an autonomic neuropathy.
      Autonomic neuropathy is a previously unexplored cause of gastric dilatation and
      intestinal dysmotility in dogs. These findings should open new directions for
      exploring pathogenic mechanisms for gastric dilatation in this species. 

PMID- 24659725
TI  - Relationship of body weight to maintenance cyclosporine a dose in canine atopic
      dermatitis.
AB  - Cyclosporine A (CsA) is a commonly prescribed and effective therapy for canine
      atopic dermatitis. The purpose of this study was to investigate the potential
      relationship between patient body weight and CsA dosing. Seventy-seven cases of
      canine atopic dermatitis managed between 2000 and 2011 were evaluated
      retrospectively. Duration of CsA therapy was at least 16 wk. Groups analyzed
      included the study population as a whole, those treated with only CsA, and those
      treated with both CsA and metoclopramide. The division between small and large
      dogs was set at 15 kg. Descriptive analysis, two-way analysis of variance,
      Pearson correlations, and a Student t test were used to analyze data. There were
      no significant differences between CsA dose and body weight regardless of method
      of analysis. Concurrent corticosteroid use, other medication use, and pruritus
      score were also analyzed over the study period. There was a significant decrease
      in CsA dose, corticosteroid dose, medication score, and pruritus score between
      the time points for all patients, but no significant relationship between those
      changes and body weight. These study findings suggest that differential CsA
      dosing is not warranted based on body weight. 

PMID- 24659726
TI  - A pilot comparison of limited versus large fluid volume resuscitation in canine
      spontaneous hemoperitoneum.
AB  - Treatment for hemorrhagic shock secondary to a spontaneous hemoperitoneum
      includes restoration of IV volume and surgical control of hemorrhage. This study
      was designed to determine if limited fluid volume resuscitation (LFVR) with
      hypertonic saline (HS) and hyperoncotic fluids (hydroxyethylstarch [HES]) results
      in more rapid cardiovascular stabilization in dogs with spontaneous
      hemoperitoneum versus conventional resuscitation (CR) with large volume
      resuscitation. Eighteen client-owned dogs presenting in hemorrhagic shock with a
      spontaneous hemoperitoneum were enrolled. Dogs were randomized to be fluid
      resuscitated with up to 90 mL/kg of an isotonic crystalloid (CR group) or up to 8
      mL/kg of 7.2% Na chloride (i.e., HS) combined with up to 10 mL/kg of 6% HES.
      Measurements of vital signs, lactate, packed cell volume (PCV), total solids
      (TS), and blood pressure were made at standard time points. The primary end point
      was time to stabilization of hemodynamic parameters (measured in min). Dogs in
      the LFVR group achieved hemodynamic stabilization significantly faster (20 min;
      range, 10-25 min) than those in the CR group (35 min; range, 15-50 min; P =
      .027). Future studies are warranted to further investigate potential benefits
      associated with LFVR in dogs with spontaneous hemoperitoneum. 

PMID- 24659727
TI  - Tolerability of lomustine in combination with cyclophosphamide in dogs with
      lymphoma.
AB  - This retrospective study describes toxicity associated with a protocol of
      lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was
      administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on
      day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over
      days 0 through 4, and all dogs received prophylactic antibiotics. Ninety
      treatments were given to the 57 dogs included in the study. Neutropenia was the
      principal toxic effect, and the overall frequency of grade 4 neutropenia after
      the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The
      mean body weight of dogs with grade 4 neutropenia (19.7 kg +/- 13.4 kg) was
      significantly less than the mean body weight of dogs that did not develop grade 4
      neutropenia (31.7 kg +/- 12.4 kg; P = .005). One dog (3%) developed hematologic
      changes suggestive of hepatotoxicity. No dogs had evidence of either renal
      toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon.
      On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU
      combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in
      tumor-bearing dogs. 

PMID- 24659728
TI  - Complete surgical removal of a very enlarged pituitary corticotroph adenoma in a
      dog.
AB  - A 13 yr old castrated male vizsla was referred to the authors' institute because
      of polyuria, polydipsia, polyphagia, and weight loss. Pituitary-dependent
      hypercortisolism (PDH) was diagnosed by hormone testing and adrenal and pituitary
      imaging. Computed tomography (CT) revealed a pituitary mass measuring 21 mm in
      width. Medical therapy was initiated with trilostane. Despite adequate control of
      the hypercortisolemia, the polyuria and polydipsia persisted and the dog
      developed neurologic signs due to the pituitary mass effect. Pituitary
      transsphenoidal debulking surgery was performed and immunocytochemistry confirmed
      a corticotroph adenoma. The dog survived for 13 mo after surgery. Postmortem
      examination revealed an empty fossa without pituitary remnants and the presence
      of a malignant pheochromocytoma in the right adrenal gland. This case report
      demonstrates, for the first time, that a large pituitary adenoma in the dog may
      be treated successfully by pituitary surgery. 

PMID- 24659729
TI  - Inside the brachycephalic nose: intranasal mucosal contact points.
AB  - The purpose of this study was to evaluate the prevalence of intranasal mucosal
      contact points in brachycephalic and normocephalic dogs. In total, 82
      brachycephalic dogs (42 pugs and 40 French bulldogs) were evaluated by rhinoscopy
      for their intranasal mucosal contact and 25 normocephalic dogs were evaluated as
      a control group. Of those, 162 brachycephalic nasal cavities were evaluable and
      140 had contact between intranasal structures (87%). Intraconchal and
      septoconchal mucosal contact points were the most commonly detected sites of
      contact. French bulldogs had a significantly higher prevalence of mucosal contact
      and had 3 mean contact points compared with 1.7 mean contact points per nasal
      cavity in pugs. Septal deviations were present in 62% of brachycephalic dogs. In
      the control group, mucosal contact points were present in only 7 of 50 nasal
      cavities (14%), and septal deviations occurred in 16% of those cases. Contact
      point average was 0.1 in large and 0.3 in small normocephalic dogs. Intranasal
      mucosal contact was identified as a common and previously unreported problem in
      brachycephalic dogs. Numerous contact points reduce the lumen of the intranasal
      passageways and indicate potential intranasal obstruction. Affected dogs might
      benefit from removal of obstructing conchae, potentially using laser-assisted
      turbinectomy. 

PMID- 24659730
TI  - Synovial myxoma in the vertebral column of a dog: MRI description and surgical
      removal.
AB  - A 12 yr old castrated male mixed-breed dog presented with a 2 wk history of
      progressive tetraparesis. Neurologic deficits included a short-strided choppy
      gait in the thoracic limbs and a long-strided proprioceptive ataxia in the pelvic
      limbs. Withdrawal reflexes were decreased bilaterally in the thoracic limbs.
      Signs were consistent with a myelopathy of the caudal cervical/cranial thoracic
      spinal cord (i.e., the sixth cervical [C] vertebra to the second thoracic [T]
      vertebra). A mass associated with the C6-C7 articular facet on the left side was
      identified on MRI of the cervical spinal cord. The lesion was hyperintense to
      spinal cord parenchyma on T2-weighted images, hypointense on T1-weighted images,
      and there was strong homogenous contrast enhancement. Significant spinal cord
      compression was associated with the lesion. The mass was removed through a C6-C7
      dorsal laminectomy and facetectomy. Histopathology of the mass was consistent
      with a synovial myxoma of the articular facet. A postoperative MRI showed
      complete surgical resection. Albeit rare, synovial myxomas should be included in
      the list of differential diagnoses for neoplasms affecting the vertebral columns
      in dogs. 

PMID- 24659731
TI  - Clinical outcome for MCTs of canine pinnae treated with surgical excision (2004
      2008).
AB  - Canine mast cell tumors (MCTs) are the most common cutaneous neoplasm in the dog.
      It has been suggested that MCT in certain locations may behave in a more
      biologically aggressive fashion than MCTs located in others; however, no
      published data are available for MCTs of canine pinnae treated with surgical
      excision. A retrospective study of 28 animals with surgical excision of MCTs of
      pinnae was completed with a medical record review and follow-up questionnaire to
      the operating veterinarian. The effect of tumor grade, clean or dirty excision,
      cartilage penetration, and mitotic index (MI) on local recurrence and survival
      time (ST) was evaluated. There was local recurrence in one dog with a grade 2 MCT
      and in seven of eight dogs with grade 3 MCTs. The median ST of animals with grade
      1 and 2 MCTs was not reached, whereas the median ST of animals with grade 3 MCTs
      was 10 mo. There was no statistical association between histologically clean and
      dirty margins and either local recurrence or ST. A prolonged disease free
      interval without local recurrence may be achieved with local excision of grade 1
      and 2 MCTs. Animals with grade 3 MCTs had a uniformly poor outcome with short
      times to local recurrence and death. 

PMID- 24659732
TI  - Increased prevalence of ametropia in children with neurofibromatosis type 1
      disease.
AB  - Neurofibromatosis type 1 disease is an autosomal dominant disorder associated
      with numerous ophthalmic and systemic manifestations. Organic causes of visual
      loss include optic pathway gliomas, orbital plexiform neurofibroma, and glaucoma.
      In this study, the authors analyzed the prevalence of ametropia as a cause for
      visual loss in children with neurofibromatosis type 1 disease younger than age 12
      years compared to matched controls. Only children with normal neuroimaging were
      evaluated. Myopia, hyperopia, astigmatism, and anisometropia were all more common
      in children with neurofibromatosis type 1 disease; however, statistically
      significant differences were observed in mild myopia and astigmatism alone. A
      higher need for optical correction was found in children with neurofibromatosis
      type 1 disease (33.3% vs 17.1% of controls, P = .049). In conclusion, children
      with neurofibromatosis type 1 disease have a higher prevalence of ametropia,
      especially mild myopia and astigmatism, often requiring optical correction.
      Routine refraction screening is recommended for limiting preventable visual loss.

PMID- 24659733
TI  - Spinal primitive neuroectodermal tumor mimicking as chronic inflammatory
      demyelination polyneuropathy: a case report and review of literature.
AB  - We report a young boy who presented with progressive weakness of lower
      extremities associated with areflexia and abnormal electrophysiological findings
      initially suggestive of chronic inflammatory demyelinating polyneuropathy.
      Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened
      descending spinal nerve roots only. Immunomodulating therapy was given but with
      limited clinical response. Repeated spine magnetic resonance imaging showed cauda
      equina and also new spinal cord extramedullary contrast enhancement. The initial
      extensive investigations including open biopsy did not point to any specific
      diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal
      peripheral primitive neuroectodermal tumor was confirmed. This case highlights
      the diagnostic challenges of the spinal peripheral primitive neuroectodermal
      tumor that could have an initial chronic inflammatory demyelinating
      polyneuropathy-like presentation. The literature review confirms that this is a
      rare condition and cauda equina origin has only been reported in adults and
      teenagers, and this is the first reported case in a young child. 

PMID- 24659734
TI  - Reference range of fetal transverse cerebellar diameter between 18 and 24 weeks
      of pregnancy in a Brazilian population.
AB  - To determine a reference range of fetal transverse cerebellar diameter in
      Brazilian population. This was a retrospective cross-sectional study with 3772
      normal singleton pregnancies between 18 and 24 weeks of pregnancy. The transverse
      cerebellar diameter was measured on the axial plane of the fetal head at the
      level of the lateral ventricles, including the thalamus, cavum septum pellucidum,
      and third ventricle. To assess the correlation between transverse cerebellar
      diameter and gestational age, polynomial equations were calculated, with
      adjustments by the determination coefficient (R2). The mean of fetal transverse
      cerebellar diameter ranged from 18.49 +/- 1.24 mm at 18 weeks to 25.86 +/- 1.66
      mm at 24 weeks of pregnancy. We observed a good correlation between transverse
      cerebellar diameter and gestational age, which was best represented by a linear
      equation: transverse cerebellar diameter: -6.21 + 1.307*gestational age (R2 =
      0.707). We determined a reference range of fetal transverse cerebellar diameter
      for the second trimester of pregnancy in Brazilian population.

PMID- 24659735
TI  - Use of the modified Atkins diet in Lennox Gastaut syndrome.
AB  - There is scanty data regarding the efficacy and tolerability of the modified
      Atkins diet in children with Lennox-Gastaut syndrome. This study was a
      retrospective review of children with Lennox-Gastaut syndrome treated with the
      modified Atkins diet from May 2009 and March 2011. The diet was initiated in
      those children who persisted to have daily seizures despite the use of at least 3
      appropriate antiepileptic drugs. Twenty-five children were started on a modified
      Atkins diet, restricting carbohydrate intake to 10 g/d. After 3 months, 2
      patients were seizure-free, and 10/25 children had >50% reduction in seizure
      frequency. At 6 months, of 11 patients on the diet, 3 were seizure free and 8 had
      >50% reduction in seizure frequency. At 1 year, all 9 children on diet had >50%
      reduction in seizure frequency. The side effects of the diet were mild. The
      modified Atkins diet was found to be effective and well tolerated in children
      with Lennox-Gastaut syndrome. 

PMID- 24659736
TI  - Social communication features in children following moderate to severe acquired
      brain injury: a cross-sectional pilot study.
AB  - We compared the social communication deficits of children with moderate to severe
      acquired brain injury or autism spectrum disorder, while accounting for the role
      of attention-deficit hyperactivity disorder (ADHD) symptoms. Parents of 20
      children aged 6 to 10 years (10 acquired brain injury; 10 autism spectrum
      disorder) completed the Social Communication Questionnaire, and Conners 3 Parent
      Short. A multivariate analysis of covariance revealed significant differences
      between groups in Social Communication Questionnaire restricted repetitive
      behavior scores, but not reciprocal social interaction or social communication.
      Multiple linear regressions indicated diagnosis did not predict reciprocal social
      interaction or social communication scores and that Conners 3 Parent Short Form
      hyperactivity scores were the strongest predictor of Social Communication
      Questionnaire reciprocal social interaction scores after accounting for age and
      Intelligence Quotient. The lack of difference in social communication deficits
      between groups may help in understanding the pathophysiology underlying the
      behavioral consequences of acquired brain injury. The link between hyperactivity
      and reciprocal interaction suggests that targeting hyperactivity may improve
      social outcomes in children following acquired brain injury. 

PMID- 24659737
TI  - Progressive myelopathy mimicking subacute combined degeneration after intrathecal
      chemotherapy.
AB  - Intrathecal chemotherapy including methotrexate is well documented for
      neurotoxicity of diverse clinical manifestation. Acute or chronic
      leukoencephalopathy is the most common type of methotrexate-induced
      neurotoxicity, and subacute myelopathy is rare. Although its pathogenesis is not
      fully understood, it is postulated that direct damage of methotrexate to the
      central nervous system plays a major part and elevated levels of homocysteine and
      its excitatory amino acid neurotransmitter metabolites (homocysteic acid and
      cysteine sulfinic acid) could mediate, in part, MTX-associated neurotoxicity. On
      the while, subacute combined degeneration is a progressive degeneration of the
      dorsal and lateral columns of the spinal cord, mostly due to vitamin B12
      deficiency. The authors report a case of a 15-year-old boy with Burkitt leukemia
      who developed progressive myelopathy after intrathecal triple therapy
      (methotrexate, cytarabine, and hydrocortisone) whose clinical and radiologic
      features were compatible with subacute combined degeneration. The pathogenic
      mechanism could be explained by biochemical alteration by methotrexate and a
      possible treatment strategy was discussed. 

PMID- 24659738
TI  - A novel SUCLA2 mutation in a Portuguese child associated with "mild"
      methylmalonic aciduria.
AB  - Succinyl-coenzyme A synthase is a mitochondrial matrix enzyme that catalyzes the
      reversible synthesis of succinate and adenosine triphosphate (ATP) from succinyl
      coenzyme A and adenosine diphosphate (ADP) in the tricarboxylic acid cycle. This
      enzyme is made up of alpha and beta subunits encoded by SUCLG1 and SUCLA2,
      respectively. We present a child with severe muscular hypotonia, dystonia,
      failure to thrive, sensorineural deafness, and dysmorphism. Metabolic
      investigations disclosed hyperlactacidemia, moderate urinary excretion of
      methylmalonic acid, and elevated levels of C4-dicarboxylic carnitine in blood. We
      identified a novel homozygous p.M329V in SUCLA2. In cultured cells, the p.M329V
      resulted in a reduced amount of the SUCLA2 protein, impaired production of
      mitochondrial ATP, and enhanced production of reactive oxygen species, which was
      partially reduced by using 5-aminoimidazole-4-carboxamide ribonucleotide in the
      culture medium. Expanding the array of SUCLA2 mutations, we suggested that
      reactive oxygen species scavengers are likely to impact on disease prognosis. 

PMID- 24659739
TI  - Repeated exposure to anesthetic ketamine can negatively impact neurodevelopment
      in infants: a prospective preliminary clinical study.
AB  - Animal experiments indicate that repeated exposure to ketamine adversely affects
      the developing brain. Whether it has the same effect on infants remains unclear.
      We recruited infants who were scheduled for 1 to 3 outpatient laser surgery
      treatments of benign facial growths with ketamine anesthesia. Patients were
      assigned to the Ket(1), Ket(2), or Ket(3) group, according to the number of
      treatments. The Bayley Scales of Infant Development-Second Edition (BSID-II) was
      used to assess neurodevelopmental outcomes before the first and after the last
      therapy. Levels of S-100beta were also measured. Bayley Scales of Infant
      Development-Second Edition scores after the last procedure were lower than those
      before the first surgery in the Ket(3) group (P < .05). S-100beta levels after
      the last procedure were significantly higher than those before the first surgery
      in all groups (P < .05). Our results suggest that 3 or more exposures to
      anesthetic ketamine have the potential to adversely affect neurodevelopment in
      infants.

PMID- 24659741
TI  - [Potential relevance of microRNAs in the diagnostics of inflammatory bowel
      diseases].
AB  - Inflammatory bowel diseases are chronic inflammatory disorders characterized by
      relapses and remissions. Several factors have been suggested to participate in
      their development, although their detailed pathogenesis still remains largely
      unknown. MicroRNAs are single strained, non-coding RNAs, consisting of 18-25
      nucleotides that regulate gene expression at the posttranscriptional level.
      Aberrant expression of microRNAs has been found in several malignant tumors.
      Recently the role of microRNAs in the pathogenesis of inflammatory-autoimmune
      disorders (such as inflammatory bowel disease) is being intensively investigated.
      Beside their pathogenic roles, microRNAs can also be exploited as diagnostic
      markers, especially in cases where the interpretation of histological data is
      difficult. In this review the authors discuss recent findings in the field of
      microRNAs in the diagnosis and pathogenesis of inflammatory bowel diseases.

PMID- 24659740
TI  - Clinical impact of gene mutations and lesions detected by SNP-array karyotyping
      in acute myeloid leukemia patients in the context of gemtuzumab ozogamicin
      treatment: results of the ALFA-0701 trial.
AB  - We recently showed that the addition of fractionated doses of gemtuzumab
      ozogamicin (GO) to standard chemotherapy improves clinical outcome of acute
      myeloid leukemia (AML) patients. In the present study, we performed mutational
      analysis of 11 genes (FLT3, NPM1, CEBPA, MLL, WT1, IDH1/2, RUNX1, ASXL1, TET2,
      DNMT3A), EVI1 overexpression screening, and 6.0 single-nucleotide polymorphism
      array (SNP-A) analysis in diagnostic samples of the 278 AML patients enrolled in
      the ALFA-0701 trial. In cytogenetically normal (CN) AML (n=146), 38% of the
      patients had at least 1 SNP-A lesion and 89% of the patients had at least 1
      molecular alteration. In multivariate analysis, the independent predictors of
      higher cumulative incidence of relapse were unfavorable karyotype (P = 0.013) and
      randomization in the control arm (P = 0.007) in the whole cohort, and MLL partial
      tandem duplications (P = 0.014) and DNMT3A mutations (P = 0.010) in CN-AML. The
      independent predictors of shorter overall survival (OS) were unfavorable
      karyotype (P <0.001) and SNP-A lesion(s) (P = 0.001) in the whole cohort, and SNP
      A lesion(s) (P = 0.006), DNMT3A mutations (P = 0.042) and randomization in the
      control arm (P = 0.043) in CN-AML. Interestingly, CN-AML patients benefited
      preferentially more from GO treatment as compared to AML patients with abnormal
      cytogenetics (hazard ratio for death, 0.52 versus 1.14; test for interaction, P =
      0.04). Although the interaction test was not statistically significant, the OS
      benefit associated with GO treatment appeared also more pronounced in FLT3
      internal tandem duplication positive than in negative patients. 

PMID- 24659742
TI  - [Epigenetic background of the most common non-oncologic gynecological diseases].
AB  - Epigenetic effects influence the function of genes regulating the main
      physiological mechanisms. Some of these environmental factors may reduce or
      inhibit the function of these genes. The environmental effects on gene function
      may result in a change of the DNA structure leading to non-heritable phenotype
      changes. Epigenetic factors play an important etiological role in the development
      of numerous diseases in obstetrics and gynecology. Uterine fibroids probably have
      a complex etiological background including epigenetic mechanisms. The
      multifactorial aetiology of endometriosis suggests key roles for immunological
      and hormonal factors in the development of the diseases. These mechanisms are
      influenced by epigenetic factors, which may serve as therapeutic targets in the
      future. The possible in utero origin of polycystic ovary syndrome determines the
      main directions of research concerning epigenetic factors in the etiological
      background, with the hope of eventual prevention and/or treatment in the
      preconceptional period as well as during pregnancy care.

PMID- 24659743
TI  - [Birth marks and neonatal skin disorders. From angel kiss to epidermolysis
      bullosa].
AB  - INTRODUCTION: At present there are no exact epidemiologic data on the prevalence
      of neonatal skin disorders and birth marks in Hungary. AIM: The aim of the
      authors was to investigate the prevalence of skin disorders in mature healthy
      neonates after birth. METHOD: The survey was carried out in the Neonatal Care
      Unit at the Department of Obstetrics and Gynaecology at the University of Szeged
      between April, 2012 and May, 2013. RESULTS: A total of 2289 newborn infants
      underwent whole-body screening skin examinations. At least one skin manifestation
      was found in 63% of the neonates. The major groups of skin disorders were
      transient benign cutaneous lesions, vascular lesions, pigmented lesions,
      traumatic, iatrogenic, congenital or acquired disorders with skin injuries,
      developmental abnormalities and benign skin tumours. The most frequent transient
      cutaneous lesions were erythema toxicum neonatorum, sebaceous hyperplasia and
      desquamation. The most common vascular lesions were naevus simplex, haemangioma
      and haemangioma precursor lesion, while the most frequently observed pigmented
      lesions were congenital melanocytic naevi and Mongolian spot. CONCLUSIONS: In the
      vast majority of cases, special treatment was not necessary, but 5.27% of the
      neonates required local dermatologic therapy, and in 9.2% of neonates follow up
      was recommended.

PMID- 24659744
TI  - [The economic burden of prostate cancer. A systematic literature overview of
      registry-based studies].
AB  - INTRODUCTION: Prostate cancer, the most frequent malignant disease in males in
      Europe, accounts for a great proportion of health expenditures. AIM: A systematic
      review of registry-based studies about the cost-of-illness and related factors of
      prostate cancer, published in the last 10 years. METHOD: A MEDLINE-based
      literature review was carried out between January 1, 2003 and October 1, 2013.
      RESULTS: Fifteen peer-reviewed articles met the criteria of interest. In
      developed countries radiotherapy, surgical treatment and hormone therapy account
      for the greatest per capita costs. In Europe early stage tumours (4-7000 ?,
      2006), while in the USA metastatic prostate cancer (19 900-25 500 $, 2004) was
      associated with highest per capita expenses. In Europe the greatest costs
      incurred within the initial treatment (6400 ?/6 months, 2008), while in the USA
      within the end-of-life care (depending on age: 62 200-93 400 $, 2010).
      CONCLUSIONS: Despite public health importance of prostate cancer, the cost-of
      illness literature from Europe is relatively small.

PMID- 24659746
TI  - Severe respiratory failure due to embolization of cyanoacrylate sclerosant.

PMID- 24659747
TI  - Healing scars: targeting pericytes to treat fibrosis.
AB  - Fibrosis, with resultant loss of organ function, is the endpoint of many
      diseases. Despite this, no effective anti-fibrotic therapies exist. The
      myofibroblast is the key cell driving fibrosis but its origins remain
      controversial. A growing body of work provides strong evidence that the pericyte,
      a perivascular cell present throughout the microvasculature, is a major
      myofibroblast precursor in multiple tissues. This review summarizes the principle
      experimental and clinical evidence underpinning this conclusion and outlines
      strategies for targeting pericyte transdifferentiation during fibrogenesis.
      Successful targeting of pro-fibrogenic pericytes has the potential to halt or
      even reverse fibrosis and thus reduce the enormous worldwide healthcare burden
      that currently exists as a result of fibrotic disease. 

PMID- 24659748
TI  - Necrobiotic xanthogranuloma.

PMID- 24659749
TI  - High Mdm4 levels suppress p53 activity and enhance its half-life in acute myeloid
      leukaemia.
AB  - Although p53 is found mutated in almost 50% of all cancers, p53 mutations in
      leukaemia are relatively rare. Acute myeloid leukaemia (AML) cells employ other
      strategies to inactivate their wild type p53 (WTp53), like the overexpression of
      the p53 negative regulators Mdm2 and Mdm4. As such, AMLs are excellent candidates
      for therapeutics involving the reactivation of their WTp53 to restrict and
      destroy cancer cells, and the Mdm2 antagonist nutlin-3 is one such promising
      agent. Using AML cell lines with WTp53, we identified stable and high levels of
      p53 in the OCI/AML-2 cell lines. We demonstrate that this nutlin-3 sensitive cell
      line overexpressed Mdm4 to sequester, stabilise and inhibit p53 in the cytoplasm.
      We also show that elevated Mdm4 competed with Mdm2-p53 interaction and therefore
      extended p53 half-life while preventing p53 transcriptional activity. Our results
      provide biochemical evidence on the dynamics of the p53-Mdm2-Mdm4 interactions in
      affecting p53 levels and activity, and unlike previously reported findings
      derived from genetically manipulated systems, AML cells with naturally high
      levels of Mdm4 remain sensitive to nutlin treatment. KEY POINTS: Endogenously
      high levels of Mdm4 inhibit and sequester p53 in AML. High levels of Mdm4 do not
      block function of Mdm2 inhibitors in AML.

PMID- 24659750
TI  - Evaluation of antifungal use in a tertiary care institution: antifungal
      stewardship urgently needed.
AB  - OBJECTIVES: To assess the quality of antifungal use, to propose a point score for
      this evaluation and to estimate the potential economic savings of an antifungal
      stewardship programme. METHODS: From December 2010 to January 2011, we identified
      100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated
      by means of a predefined score that considered indication, drug selection,
      dosage, adjustments after microbiology results, switching to an oral agent and
      length of treatment. Total antifungal prescriptions [in defined daily doses
      (DDDs) and days of therapy (DOTs)] and potential cost savings were calculated.
      RESULTS: Overall, 43% of prescriptions came from medical departments, 25% from
      haematology/oncology and 17% from intensive care units. The main reasons for
      starting antifungals were empirical (42%), pre-emptive (20%) and targeted
      treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in
      other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%;
      no switch from intravenous to oral administration, 20%; no adjustment after
      microbiological results, 35%; and length of therapy, 27%. The number of
      antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was
      1556, which added a direct cost of ?219 364. Only 51.3% of DOTs were considered
      optimal. The potential estimated savings would be ?50 536. CONCLUSIONS: Major
      efforts should be made to improve the selection and duration of antifungal
      therapy. Our study demonstrated the potential cost savings that could be achieved
      by optimizing antifungal therapy. A stewardship programme should include an
      instrument to objectively evaluate the adequacy of antifungal use.

PMID- 24659751
TI  - Serratia marcescens harbouring SME-type class A carbapenemases in Canada and the
      presence of blaSME on a novel genomic island, SmarGI1-1.
AB  - OBJECTIVES: An increasing prevalence since 2010 of Serratia marcescens harbouring
      the Ambler class A carbapenemase SME prompted us to further characterize these
      isolates. METHODS: Isolates harbouring bla(SME) were identified by PCR and
      sequencing. Phenotypic analysis for carbapenemase activity was carried out by a
      modified Hodge test and a modified Carba NP test. Antimicrobial susceptibilities
      were determined by Etest and Vitek 2. Typing was by PFGE of macrorestriction
      digests. Whole-genome sequencing of three isolates was carried out to
      characterize the genomic region harbouring the bla(SME)-type genes. RESULTS: All
      S. marcescens harbouring SME-type enzymes could be detected using a modified
      Carba NP test. Isolates harbouring bla(SME) were resistant to penicillins and
      carbapenems, but remained susceptible to third-generation cephalosporins, as well
      as fluoroquinolones and trimethoprim/sulfamethoxazole. Isolates exhibited diverse
      genetic backgrounds, though 57% of isolates were found in three clusters.
      Analysis of whole-genome sequence data from three isolates revealed that the
      bla(SME) gene occurred in a novel cryptic prophage genomic island, SmarGI1-1.
      CONCLUSIONS: There has been an increasing occurrence of S. marcescens harbouring
      bla(SME) in Canada since 2010. The bla(SME) gene was found on a genomic island,
      SmarGI1-1, that can be excised and circularized, which probably contributes to
      its dissemination amongst S. marcescens.

PMID- 24659752
TI  - Clinical usefulness of measuring red blood cell distribution width in patients
      with systemic sclerosis.
AB  - OBJECTIVE: Red blood cell distribution width (RDW) is a biomarker quantifying the
      variability of red blood cell size in peripheral blood. Elevated RDW has been
      found to be an independent prognostic factor for cardiovascular events. SSc is
      characterized by generalized micro- and macroangiopathy. Our aim was to
      investigate RDW as a potential biomarker for the assessment of the severity of
      vascular involvement. METHODS: One hundred and sixty-eight consecutive SSc
      patients--62 with dcSSc and 106 with lcSSc--were investigated at baseline and
      after 1-year of follow-up. Measurements in 93 patients with primary RP and 40
      healthy subjects served as controls. RESULTS: The median RDW value of patients
      with SSc was higher [14.2% (25th-75th percentiles 13.5-14.8%) compared with the
      group of primary RP patients [13.9% (13.4-14.4%); P < 0.05) and healthy
      volunteers [13.6% (13.2-13.8%; P < 0.01]. dcSSc and anti-topoisomerase antibody
      positive cases showed elevated RDW values compared with lcSSc and anti
      topoisomerase antibody-negative cases (P < 0.05). RDW showed a positive
      correlation with inflammatory markers, including ESR (P < 0.05) and CRP (P <
      0.05), and a negative correlation with forced vital capacity (P < 0.05) and
      diffusing capacity of the lung for carbon monoxide (DLCO) (P < 0.05) during the
      follow-up. An increase in RDW of >5% during follow-up was associated with an
      average 8.9% decrease in left ventricular ejection fraction (LVEF) and 7% in DLCO
      and these associations were independent of each other. CONCLUSION: RDW in SSc may
      represent an integrative measure of multiple pathological processes including
      extensive vasculopathy, fibrosis or ongoing inflammation. An increase in RDW may
      indicate an impairment of cardiorespiratory function.

PMID- 24659753
TI  - Bone marrow oedema assessment by magnetic resonance imaging in rheumatoid
      arthritis wrist and metacarpophalangeal joints: the importance of field strength,
      coil type and image resolution.
AB  - OBJECTIVE: The aim of this study was to examine the influence of different MRI
      unit field strengths, coil types and image resolutions on the OMERACT RA MRI
      scoring system (RAMRIS) of bone marrow oedema (BME) and image quality. METHODS:
      Forty-one patients and 12 healthy controls participated in this cross-sectional
      study. Coronal short tau inversion recovery (STIR) and T1-weighted sequences were
      obtained at 0.23, 0.6, 1.5 and 3T using flex coils (Flex). Additional STIR
      sequences were obtained with phased array extremity coils (Extr) (at 0.6 and
      1.5T) and higher resolution (at 1.5T). In otal, 338 STIR image sets were
      anonymized and scored according to RAMRIS and parameters of image quality were
      measured. RESULTS: The BME sum scores were similar overall when comparing the
      different MRI units, coil types and voxel sizes, yet significantly higher at the
      higher resolution of 1.5T Extr compared with 0.23T Flex (P = 0.004), 0.6T Flex (P
      = 0.03), 1.5T Flex (P = 0.05) and 3T Flex (P = 0.001). Mean differences were
      relatively minor (0-3.5). Intrareader reliability of BME scores was high
      [intraclass correlation coefficient >= 0.90 for all except 0.23T (0.81) and
      percentage exact agreement 81-88%]. The smallest detectable difference was better
      at 0.6, 1.5 and 3T (9-29% of maximum value) than at 0.23T (40%). Image quality
      was lowest at 0.23T. CONCLUSION: No major, consistent differences were found
      between BME scores using STIR sequences obtained at different field strengths,
      coil types and image resolutions, suggesting that these are equally suited for
      assessment of BME in RA. However, parameters of image quality and intrareader
      reliability (favouring 0.6, 1.5 and 3T) should be considered when selecting the
      MRI acquisition strategy.

PMID- 24659754
TI  - Naltrexone metabolism and concomitant drug concentrations in chronic pain
      patients.
AB  - Naltrexone is effective in treating opioid dependence by blocking u, kappa and
      delta opiate receptors. Naltrexone is mainly metabolized to an active metabolite
      6beta-naltrexol by dihydrodiol dehydrogenase enzymes. Concomitant opioids will
      not be effective while patients are taking this antagonist. This was a
      retrospective analysis of urinary excretion data collected from patients being
      treated with pain between November 2011 and May 2012. Naltrexone, 6beta-naltrexol
      and concomitant opiate concentrations were measured by liquid chromatography
      tandem mass spectrometry. Interpatient variability was calculated from first
      visit specimens, and intrapatient variability was calculated from patients with
      two or more visits. Relationships of the metabolic ratio (MR; 6beta
      naltrexol/naltrexone) with age, gender and urinary pH were also explored. From 88
      first-visit patient specimens, the median MR was 3.28 (range 0.73-17.42). The MR
      was higher in women than men (5.00 vs. 3.14, P< 0.05). The MR showed no
      association based on age and urinary pH. Eighteen of 88 patients taking oral
      naltrexone tested positive for concomitant opiate use. Urinary MRs of 6beta
      naltrexol/naltrexone were highly variable, which may contribute to variability in
      efficacy, toxicity and patient willingness to take naltrexone as directed. Twenty
      percent of patients tested positive for opiates and naltrexone, thus showing the
      importance of monitoring patients taking naltrexone. 

PMID- 24659757
TI  - Society of correctional physicians calls for caution placing mentally ill in
      segregation: an important band-aid.

PMID- 24659755
TI  - Synovial inflammation assessed by ultrasonography correlates with MRI-proven
      osteitis in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to explore whether assessment of synovial
      inflammation by ultrasonography correlates with MRI-proven osteitis in patients
      with RA. METHODS: Thirty RA patients who fulfilled 2010 RA classification
      criteria and were naive to DMARDs, including biologics and glucocorticoids, were
      consecutively enrolled in this study. Grey scale (GS) and power Doppler (PD)
      images of articular synovitis and bone erosion in both wrist and MCP joints were
      evaluated by the method proposed by the European League Against Rheumatism. MRI
      proven osteitis of the identical sites was also evaluated within 3 days using the
      RA MRI scoring system (RAMRIS). The Cochran-Armitage test and Spearman's
      correlation coefficient were used to investigate the correlation of each US
      finding with MRI-proven osteitis. RESULTS: MRI-proven osteitis was found in 8.3%
      of MCP joints and 48.3% of wrist joints. Its prevalence was increased in the
      joints where the GS or PD grade of articular synovitis was 2 or 3. In addition,
      MRI-proven osteitis was found preferentially in the joints positive for bone
      erosion on US. A clear correlation was demonstrated between the GS or PD grade of
      articular synovitis or the presence of US bone erosion and RAMRIS osteitis score
      in both MCP joints and wrist joints. CONCLUSION: Our data indicate that joint
      injury assessed by US correlates with MRI-proven osteitis in patients with RA.

PMID- 24659758
TI  - Seroconversion risk perception among jail populations: a call for gender-specific
      HIV prevention programming.
AB  - The prevalence of HIV/AIDS infection among prisoners is 3 to 4 times higher than
      in the U.S. population. Given that one in seven HIV-positive Americans pass
      through a correctional facility every year, the criminal justice system is in an
      ideal position to aggressively implement effective HIV education, treatment, and
      prevention. This study examines barriers to the effective delivery of these
      services and evaluates differences in risk perception among nearly 600 female and
      male inmates. The results underscore gender differences in Perceived Risk of
      Seroconversion and Exposure to HIV Education, suggesting that jails should
      implement gender-specific HIV prevention programming. 

PMID- 24659759
TI  - Patient health satisfaction survey in connecticut correctional facilities.
AB  - Although routine in the community, patient satisfaction surveys are relatively
      rare in correctional settings. This article describes the development of an
      instrument specifically adapted to the correctional environment and population,
      the statewide implementation of the survey, the initial results, and the quality
      improvement initiatives evolving from this effort. 

PMID- 24659760
TI  - Comorbid mental illness and poor physical function among newly admitted inmates
      in Connecticut's jails.
AB  - The prevalence of co-occurring mental illness and poor physical functioning among
      inmates, and whether there are differences according to age or gender, is largely
      unknown. Of the 315 new inmate admissions into Connecticut's jails with a current
      psychiatric diagnosis, 97 (30.9%) had poor physical function. Compared with
      inmates aged 18 to 24, those aged 25 to 39 and those >= 40 had increasingly
      higher likelihoods of having poor physical function overall, and among men and
      women separately. Whereas women were more likely to report poor physical
      functioning than men overall and within age groups 18 to 24 and 25 to 39, the
      effect of gender was nonsignificant in the oldest age group. Future research
      should determine whether poor physical function is associated with worse health
      related outcomes among inmates with mental illness. 

PMID- 24659761
TI  - Benefits of a department of corrections partnership with a health sciences
      university: New Jersey's experience.
AB  - More than half of the state prisons in the United States outsource health care.
      While most states contract with private companies, a small number of states have
      reached out to their health science universities to meet their needs for health
      care of prisoners. New Jersey is the most recent state to form such an agreement.
      This article discusses the benefits of such a model for New Jersey's Department
      of Corrections and for New Jersey's health sciences university, the Rutgers
      University, formerly the University of Medicine and Dentistry of New Jersey. The
      benefits for both institutions should encourage other states to participate in
      such affiliations. 

PMID- 24659762
TI  - An outbreak of Candida albicans folliculitis masquerading as Malassezia
      folliculitis in a prison population.
AB  - Several inmates from a non-air-conditioned prison were sent to the University of
      Texas Medical Branch dermatology clinic for unexplained eruptions not responding
      to various treatments. They were initially diagnosed with Malassezia folliculitis
      based on clinical examination and histological findings. The patients' cultures
      from skin scrapings, however, revealed Candida albicans confirmed by growth on
      Mycosel agar and further by the germ tube production method. Five cases were
      brought to the clinic, but at least 30 other inmates were reported to have
      similar cutaneous eruptions. Given that these patients were generally
      immunocompetent, this is a rare finding. Factors favoring pseudohyphal growth for
      these patients included use of topical steroids and/or systemic antibiotics and
      hot and humid climate. All patients' folliculitis resolved with fluconazole
      and/or antifungal cream with no further complications. 

PMID- 24659763
TI  - Surveillance of suicidal and nonsuicidal self-injury in the New York City jail
      system.
AB  - Suicide and nonsuicidal self-injury represent significant causes of morbidity and
      mortality in jail settings. The New York City Department of Health and Mental
      Hygiene instituted a database of suicidal and nonsuicidal self-injuries in 2007.
      Between 2007 and 2011, there were eight deaths by suicide and 2,514 acts of self
      injury, with the annual rate of self-injury increasing significantly throughout
      this time period. The most frequent methods of self-injury were lacerations
      (816), ligature tied around the neck (569), attempted overdose (501), and
      swallowed foreign objects (372). This review led to improvements in surveillance
      as well as improvement of the newly implemented electronic health record. 

PMID- 24659765
TI  - Intracellular hydrogen peroxide and superoxide poison 3-deoxy-D
      arabinoheptulosonate 7-phosphate synthase, the first committed enzyme in the
      aromatic biosynthetic pathway of Escherichia coli.
AB  - In Escherichia coli, aromatic compound biosynthesis is the process that has shown
      the greatest sensitivity to hydrogen peroxide stress. This pathway has long been
      recognized to be sensitive to superoxide as well, but the molecular target was
      unknown. Feeding experiments indicated that the bottleneck lies early in the
      pathway, and the suppressive effects of fur mutations and manganese
      supplementation suggested the involvement of a metalloprotein. The 3-deoxy-D
      arabinoheptulosonate 7-phosphate synthase (DAHP synthase) activity catalyzes the
      first step in the pathway, and it is provided by three isozymes known to rely
      upon a divalent metal. This activity progressively declined when cells were
      stressed with either oxidant. The purified enzyme was activated more strongly by
      ferrous iron than by other metals, and only this metalloform could be inactivated
      by hydrogen peroxide or superoxide. We infer that iron is the prosthetic metal in
      vivo. Both oxidants displace the iron atom from the enzyme. In peroxide-stressed
      cells, the enzyme accumulated as an apoprotein, potentially with an oxidized
      cysteine residue. In superoxide-stressed cells, the enzyme acquired a
      nonactivating zinc ion in its active site, an apparent consequence of the
      repeated ejection of iron. Manganese supplementation protected the activity in
      both cases, which matches the ability of manganese to metallate the enzyme and to
      provide substantial oxidant-resistant activity. DAHP synthase thus belongs to a
      family of mononuclear iron-containing enzymes that are disabled by oxidative
      stress. To date, all the intracellular injuries caused by physiological doses of
      these reactive oxygen species have arisen from the oxidation of reduced iron
      centers.

PMID- 24659766
TI  - The Salmonella enterica serovar Typhi LeuO global regulator forms tetramers:
      residues involved in oligomerization, DNA binding, and transcriptional
      regulation.
AB  - LeuO is a LysR-type transcriptional regulator (LTTR) that has been described to
      be a global regulator in Escherichia coli and Salmonella enterica, since it
      positively and negatively regulates the expression of genes involved in multiple
      biological processes. LeuO is comprised of an N-terminal DNA-binding domain (DBD)
      with a winged helix-turn-helix (wHTH) motif and of a long linker helix (LH)
      involved in dimerization that connects the DBD with the C-terminal effector
      binding domain (EBD) or regulatory domain (RD; which comprises subdomains RD-I
      and RD-II). Here we show that the oligomeric structure of LeuO is a tetramer that
      binds with high affinity to DNA. A collection of single amino acid substitutions
      in the LeuO DBD indicated that this region is involved in oligomerization, in
      positive and negative regulation, as well as in DNA binding. Mutants with point
      mutations in the central and C-terminal regions of RD-I were affected in
      transcriptional activation. Deletion of the RD-II and RD-I C-terminal subdomains
      affected not only oligomerization but also DNA interaction, showing that they are
      involved in positive and negative regulation. Together, these data demonstrate
      that not only the C terminus but also the DBD of LeuO is involved in oligomer
      formation; therefore, each LeuO domain appears to act synergistically to maintain
      its regulatory functions in Salmonella enterica serovar Typhi. 

PMID- 24659767
TI  - Characterization of BCAM0224, a multifunctional trimeric autotransporter from the
      human pathogen Burkholderia cenocepacia.
AB  - Members of the trimeric autotransporter adhesin (TAA) family play a crucial role
      in adhesion of Gram-negative pathogens to host cells. Moreover, these proteins
      are multifunctional virulence factors involved in several other biological
      traits, including invasion into host cells and evasion of the host immune system.
      In cystic fibrosis epidemic Burkholderia cenocepacia strain J2315, we identified
      a unique TAA (BCAM0224)-encoding gene, previously described as being implicated
      in virulence. Here, we characterized this multifunctional protein, trying to
      establish its role in B. cenocepacia pathogenicity. We show that BCAM0224 occurs
      on the bacterial surface and adopts a trimeric conformation. Furthermore, we
      demonstrated that BCAM0224 is needed for earlier stages of biofilm formation and
      is required for swarming motility. In addition, BCAM0224 plays an important role
      in evasion of the human innate immune system, providing resistance against the
      bactericidal activity of serum via the complement classical pathway. Finally,
      BCAM0224 mediates bacterial adhesion to and invasion of cultured human bronchial
      epithelial cells. Together, these data reveal the high versatility of the
      BCAM0224 protein as a virulence factor in the pathogenic bacterium B.
      cenocepacia. 

PMID- 24659768
TI  - Global metabolic response of Enterococcus faecalis to oxygen.
AB  - Oxygen and oxidative stress have become relevant components in clarifying the
      mechanism that weakens bacterial cells in parallel to the mode of action of
      bactericidal antibiotics. Given the importance of oxidative stress in the overall
      defense mechanism of bacteria and their apparent role in the antimicrobial mode
      of action, it is important to understand how bacteria respond to this stress at a
      metabolic level. The aim of this study was to determine the impact of oxygen on
      the metabolism of the facultative anaerobe Enterococcus faecalis using continuous
      culture, metabolomics, and (13)C enrichment of metabolic intermediates. When E.
      faecalis was rapidly transitioned from anaerobic to aerobic growth, cellular
      metabolism was directed toward intracellular glutathione production and
      glycolysis was upregulated 2-fold, which increased the supply of critical
      metabolite precursors (e.g., glycine and glutamate) for sulfur metabolism and
      glutathione biosynthesis as well as reducing power for cellular respiration in
      the presence of hemin. The ultimate metabolic response of E. faecalis to an
      aerobic environment was the upregulation of fatty acid metabolism and benzoate
      degradation, which was linked to important changes in the bacterial membrane
      composition as evidenced by changes in membrane fatty acid composition and the
      reduction of membrane-associated demethylmenaquinone. These key metabolic
      pathways associated with the response of E. faecalis to oxygen may represent
      potential new targets to increase the susceptibility of this bacterium to
      bactericidal drugs. 

PMID- 24659769
TI  - Streptococcus pneumoniae phosphotyrosine phosphatase CpsB and alterations in
      capsule production resulting from changes in oxygen availability.
AB  - Streptococcus pneumoniae produces a protective capsular polysaccharide whose
      production must be modulated for bacterial survival within various host niches.
      Capsule production is affected in part by a phosphoregulatory system comprised of
      CpsB, CpsC, and CpsD. Here, we found that growth of serotype 2 strain D39 under
      conditions of increased oxygen availability resulted in decreased capsule levels
      concurrent with an ~5-fold increase in Cps2B-mediated phosphatase activity. The
      change in Cps2B phosphatase activity did not result from alterations in the
      levels of either the cps2B transcript or the Cps2B protein. Recombinant Cps2B
      expressed in Escherichia coli similarly exhibited increased phosphatase activity
      under conditions of high-oxygen growth. S. pneumoniae D39 derivatives with
      defined deletion or point mutations in cps2B demonstrated reduced phosphatase
      activity with corresponding increases in levels of Cps2D tyrosine
      phosphorylation. There was, however, no correlation between these phenotypes and
      the level of capsule production. During growth under reduced-oxygen conditions,
      the Cps2B protein was essential for parental levels of capsule, but phosphatase
      activity alone could be eliminated without an effect on capsule. Under increased
      oxygen conditions, deletion of cps2B did not affect capsule levels. These results
      indicate that neither Cps2B phosphatase activity nor Cps2D phosphorylation levels
      per se are determinants of capsule levels, whereas the Cps2B protein is important
      for capsule production during growth under conditions of reduced but not enhanced
      oxygen availability. Roles for factors outside the capsule locus, possible
      interactions between capsule regulatory proteins, and links to other cellular
      processes are also suggested by the results described in this study. 

PMID- 24659770
TI  - Identification of a novel nutrient-sensing histidine kinase/response regulator
      network in Escherichia coli.
AB  - When carbon sources become limiting for growth, bacteria must choose which of the
      remaining nutrients should be used first. We have identified a nutrient-sensing
      signaling network in Escherichia coli that is activated at the transition to
      stationary phase. The network is composed of the two histidine kinase/response
      regulator systems YehU/YehT and YpdA/YpdB and their target proteins, YjiY and
      YhjX (both of which are membrane-integrated transporters). The peptide/amino acid
      responsive YehU/YehT system was found to have a negative effect on expression of
      the target gene, yhjX, of the pyruvate-responsive YpdA/YpdB system, while the
      YpdA/YpdB system stimulated expression of yjiY, the target of the YehU/YehT
      system. These effects were confirmed in mutants lacking any of the genes for the
      three primary components of either system. Furthermore, an in vivo interaction
      assay based on bacterial adenylate cyclase detected heteromeric interactions
      between the membrane-bound components of the two systems, specifically, between
      the two histidine kinases and the two transporters, which is compatible with the
      formation of a larger signaling unit. Finally, the carbon storage regulator A
      (CsrA) was shown to be involved in posttranscriptional regulation of both yjiY
      and yhjX. 

PMID- 24659771
TI  - The highly conserved MraZ protein is a transcriptional regulator in Escherichia
      coli.
AB  - The mraZ and mraW genes are highly conserved in bacteria, both in sequence and in
      their position at the head of the division and cell wall (dcw) gene cluster.
      Located directly upstream of the mraZ gene, the Pmra promoter drives the
      transcription of mraZ and mraW, as well as many essential cell division and cell
      wall genes, but no regulator of Pmra has been found to date. Although MraZ has
      structural similarity to the AbrB transition state regulator and the MazE
      antitoxin and MraW is known to methylate the 16S rRNA, mraZ and mraW null mutants
      have no detectable phenotypes. Here we show that overproduction of Escherichia
      coli MraZ inhibited cell division and was lethal in rich medium at high induction
      levels and in minimal medium at low induction levels. Co-overproduction of MraW
      suppressed MraZ toxicity, and loss of MraW enhanced MraZ toxicity, suggesting
      that MraZ and MraW have antagonistic functions. MraZ-green fluorescent protein
      localized to the nucleoid, suggesting that it binds DNA. Consistent with this
      idea, purified MraZ directly bound a region of DNA containing three direct
      repeats between Pmra and the mraZ gene. Excess MraZ reduced the expression of an
      mraZ-lacZ reporter, suggesting that MraZ acts as a repressor of Pmra, whereas a
      DNA-binding mutant form of MraZ failed to repress expression. Transcriptome
      sequencing (RNA-seq) analysis suggested that MraZ also regulates the expression
      of genes outside the dcw cluster. In support of this, purified MraZ could
      directly bind to a putative operator site upstream of mioC, one of the repressed
      genes identified by RNA-seq. 

PMID- 24659772
TI  - A small heat shock protein enables Escherichia coli to grow at a lethal
      temperature of 50 degrees C conceivably by maintaining cell envelope integrity.
AB  - It is essential for organisms to adapt to fluctuating growth temperatures.
      Escherichia coli, a model bacterium commonly used in research and industry, has
      been reported to grow at a temperature lower than 46.5 degrees C. Here we report
      that the heterologous expression of the 17-kDa small heat shock protein from the
      nematode Caenorhabditis elegans, CeHSP17, enables E. coli cells to grow at 50
      degrees C, which is their highest growth temperature ever reported. Strikingly,
      CeHSP17 also rescues the thermal lethality of an E. coli mutant deficient in
      degP, which encodes a protein quality control factor localized in the periplasmic
      space. Mechanistically, we show that CeHSP17 is partially localized in the
      periplasmic space and associated with the inner membrane of E. coli, and it helps
      to maintain the cell envelope integrity of the E. coli cells at the lethal
      temperatures. Together, our data indicate that maintaining the cell envelope
      integrity is crucial for the E. coli cells to grow at high temperatures and also
      shed new light on the development of thermophilic bacteria for industrial
      application. 

PMID- 24659773
TI  - YlxM is a newly identified accessory protein that influences the function of
      signal recognition particle pathway components in Streptococcus mutans.
AB  - Streptococcus mutans is a cariogenic oral pathogen whose virulence is determined
      largely by its membrane composition. The signal recognition particle (SRP)
      protein-targeting pathway plays a pivotal role in membrane biogenesis. S. mutans
      SRP pathway mutants demonstrate growth defects, cannot contend with environmental
      stress, and exhibit multiple changes in membrane composition. This study sought
      to define a role for ylxM, which in S. mutans and numerous other bacteria resides
      directly upstream of the ffh gene, encoding a major functional element of the
      bacterial SRP. YlxM was observed as a produced protein in S. mutans. Its
      predicted helix-turn-helix motif suggested that it has a role as a
      transcriptional regulator of components within the SRP pathway; however, no
      evidence of transcriptional regulation was found. Instead, capture enzyme-linked
      immunosorbent assay (ELISA), affinity chromatography, and bio-layer
      interferometry (BLI) demonstrated that S. mutans YlxM interacts with the SRP
      components Ffh and small cytoplasmic RNA (scRNA) but not with the SRP receptor
      FtsY. In the absence of FtsY, YlxM increased the GTP hydrolysis activity of Ffh
      alone and in complex with scRNA. However, in the presence of FtsY, YlxM caused an
      overall diminution of net GTPase activity. Thus, YlxM appears to modulate GTP
      hydrolysis, a process necessary for proper recycling of SRP pathway components.
      The presence of YlxM conferred a significant competitive growth advantage under
      nonstress and acid stress conditions when wild-type and ylxM mutant strains were
      cultured together. Our results identify YlxM as a component of the S. mutans SRP
      and suggest a regulatory function affecting GTPase activity. 

PMID- 24659774
TI  - SearchDOGS bacteria, software that provides automated identification of
      potentially missed genes in annotated bacterial genomes.
AB  - We report the development of SearchDOGS Bacteria, software to automatically
      detect missing genes in annotated bacterial genomes by combining BLAST searches
      with comparative genomics. Having successfully applied the approach to yeast
      genomes, we redeveloped SearchDOGS to function as a standalone, downloadable
      package, requiring only a set of GenBank annotation files as input. The software
      automatically generates a homology structure using reciprocal BLAST and a synteny
      based method; this is followed by a scan of the entire genome of each species for
      unannotated genes. Results are provided in a HTML interface, providing
      coordinates, BLAST results, syntenic location, omega values (Ka/Ks, where Ks is
      the number of synonymous substitutions per synonymous site and Ka is the number
      of nonsynonymous substitutions per nonsynonymous site) for protein conservation
      estimates, and other information for each candidate gene. Using SearchDOGS
      Bacteria, we identified 155 gene candidates in the Shigella boydii sb227 genome,
      including 56 candidates of length < 60 codons. SearchDOGS Bacteria has two major
      advantages over currently available annotation software. First, it outperforms
      current methods in terms of sensitivity and is highly effective at identifying
      small or highly diverged genes. Second, as a freely downloadable package, it can
      be used with unpublished or confidential data. 

PMID- 24659775
TI  - TMJ Disc Displacement without Reduction Management: A Systematic Review.
AB  - Various interventions have been used for the management of patients with
      temporomandibular joint (TMJ) disc displacement without reduction (DDwoR), but
      their clinical effectiveness remains unclear. This systematic review investigated
      the effects of these interventions and is reported in accordance with Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      Electronic and manual searches up to November 1, 2013, were conducted for English
      language, peer-reviewed, publications of randomized clinical trials comparing any
      form of conservative or surgical interventions for patients with clinical and/or
      radiologic diagnosis of acute or chronic DDwoR. Two primary outcomes (TMJ pain
      intensity and maximum mouth opening) and a number of secondary outcomes were
      examined. Two reviewers performed data extraction and risk of bias assessment.
      Data collection and analysis were performed according to Cochrane
      recommendations. Twenty studies involving 1,305 patients were included. Data
      analysis involved 21 comparisons between a variety of interventions, either
      between interventions, or between intervention and placebo or no intervention.
      Meta-analysis on homogenous groups was conducted in 4 comparisons. In most
      comparisons made, there were no statistically significant differences between
      interventions relative to primary outcomes at short- or long-term follow-up (p >
      .05). In a separate analysis, however, the majority of reviewed interventions
      reported significantly improved primary outcome measures from their baseline
      levels over time (p < .05). Evidence levels, however, are currently insufficient
      for definitive conclusions, because the included studies were too heterogeneous
      and at an unclear to high risk of bias. In view of the comparable therapeutic
      effects, paucity of high-quality evidence, and the greater risks and costs
      associated with more complex interventions, patients with symptomatic DDwoR
      should be initially treated by the simplest and least invasive intervention. 

PMID- 24659777
TI  - Budapest Declaration: IADR-GOHIRA(r).

PMID- 24659776
TI  - Primary cilia integrate hedgehog and Wnt signaling during tooth development.
AB  - Many ciliopathies have clinical features that include tooth malformations but how
      these defects come about is not clear. Here we show that genetic deletion of the
      motor protein Kif3a in dental mesenchyme results in an arrest in odontogenesis.
      Incisors are completely missing, and molars are enlarged in
      Wnt1(Cre+)Kif3a(fl/fl) embryos. Although amelogenesis and dentinogenesis initiate
      in the molar tooth bud, both processes terminate prematurely. We demonstrate that
      loss of Kif3a in dental mesenchyme results in loss of Hedgehog signaling and gain
      of Wnt signaling in this same tissue. The defective dental mesenchyme then
      aberrantly signals to the dental epithelia, which prompts an up-regulation in the
      Hedgehog and Wnt responses in the epithelia and leads to multiple attempts at
      invagination and an expanded enamel organ. Thus, the primary cilium integrates
      Hedgehog and Wnt signaling between dental epithelia and mesenchyme, and this
      cilia-dependent integration is required for proper tooth development. 

PMID- 24659779
TI  - Development of a membrane-anchored chemerin receptor agonist as a novel modulator
      of allergic airway inflammation and neuropathic pain.
AB  - The chemerin receptor (CMKLR1) is a G protein-coupled receptor found on select
      immune, epithelial, and dorsal root ganglion/spinal cord neuronal cells. CMKLR1
      is primarily coupled to the inhibitory G protein, Galphai, and has been shown to
      modulate the resolution of inflammation and neuropathic pain. CMKLR1 is activated
      by both lipid and peptide agonists, resolvin E1 and chemerin, respectively.
      Notably, these ligands have short half-lives. To expedite the development of long
      acting, stable chemerin analogs as candidate therapeutics, we used membrane
      tethered ligand technology. Membrane-tethered ligands are recombinant proteins
      comprised of an extracellular peptide ligand, a linker sequence, and an anchoring
      transmembrane domain. Using this technology, we established that a 9-amino acid
      tethered chemerin fragment (amino acids 149-157) activates both mouse and human
      CMKLR1 with efficacy exceeding that of the full-length peptide (amino acids 21
      157). To enable in vivo delivery of a corresponding soluble membrane anchored
      ligand, we generated lipidated analogs of the 9-amino acid fragment.
      Pharmacological assessment revealed high potency and wash resistance (an index of
      membrane anchoring). When tested in vivo, a chemerin SMAL decreased allergic
      airway inflammation and attenuated neuropathic pain in mice. This compound
      provides a prototype membrane-anchored peptide for the treatment of inflammatory
      disease. A parallel approach may be applied to developing therapeutics targeting
      other peptide hormone G protein-coupled receptors. 

PMID- 24659780
TI  - An ancient relative of cyclooxygenase in cyanobacteria is a linoleate 10S
      dioxygenase that works in tandem with a catalase-related protein with specific
      10S-hydroperoxide lyase activity.
AB  - In the course of exploring the scope of catalase-related hemoprotein reactivity
      toward fatty acid hydroperoxides, we detected a novel candidate in the
      cyanobacterium Nostoc punctiforme PCC 73102. The immediate neighboring upstream
      gene, annotated as "cyclooxygenase-2," appeared to be a potential fatty acid heme
      dioxygenase. We cloned both genes and expressed the cDNAs in Escherichia coli,
      confirming their hemoprotein character. Oxygen electrode recordings demonstrated
      a rapid (>100 turnovers/s) reaction of the heme dioxygenase with oleic and
      linoleic acids. HPLC, including chiral column analysis, UV, and GC-MS of the
      oxygenated products, identified a novel 10S-dioxygenase activity. The catalase
      related hemoprotein reacted rapidly and specifically with linoleate 10S
      hydroperoxide (>2,500 turnovers/s) with a hydroperoxide lyase activity specific
      for the 10S-hydroperoxy enantiomer. The products were identified by NMR as (8E)10
      oxo-decenoic acid and the C8 fragments, 1-octen-3-ol and 2Z-octen-1-ol, in ~3:1
      ratio. Chiral HPLC analysis established strict enzymatic control in formation of
      the 3R alcohol configuration (99% enantiomeric excess) and contrasted with
      racemic 1-octen-3-ol formed in reaction of linoleate 10S-hydroperoxide with
      hematin or ferrous ions. The Nostoc linoleate 10S-dioxygenase, the sequence of
      which contains the signature catalytic sequence of cyclooxygenases and fungal
      linoleate dioxygenases (YRWH), appears to be a heme dioxygenase ancestor. The
      novel activity of the lyase expands the known reactions of catalase-related
      proteins and functions in Nostoc in specific transformation of the 10S
      hydroperoxylinoleate. 

PMID- 24659781
TI  - Tight junctional localization of claudin-16 is regulated by syntaxin 8 in renal
      tubular epithelial cells.
AB  - Claudin-16 (CLDN16) regulates the paracellular reabsorption of Mg(2+) in the
      thick ascending limb of Henle's loop. However, the mechanism regulating the tight
      junctional localization of CLDN16 remains unknown. In yeast two-hybrid systems,
      we found that CLDN16 bound to syntaxin 8 (STX8), a target soluble N
      ethylmaleimide-sensitive factor attachment protein receptor. We have examined the
      effect of STX8 on the localization and function of CLDN16 using Madin-Darby
      canine kidney cells expressing FLAG-tagged CLDN16. A pulldown assay showed that
      the carboxyl cytoplasmic region of human CLDN16 bound to STX8. CLDN16 was
      localized in the thick ascending limb, whereas STX8 was widely distributed
      throughout the rat kidney. An association between CLDN16 and STX8 was observed in
      rat renal homogenates and Madin-Darby canine kidney cells. STX8 siRNA decreased
      the cell surface localization of CLDN16 and transepithelial electrical resistance
      and permeability to Mg(2+) but increased the co-localization of CLDN16 with early
      endosome and lysosome markers. Dephosphorylation of CLDN16 by protein kinase A
      inhibitors and S217A mutant, a dephosphorylated form, decreased the association
      with STX8 and the cell surface localization of CLDN16. Recycling assays indicated
      that STX8 siRNA decreased the trafficking of CLDN16 to the plasma membrane
      without affecting endocytosis. Dominant negative Rab11 and recycling inhibitor
      primaquine decreased the cell surface localization of CLDN16, which was similar
      to that in STX8 siRNA-transfected cells. These results suggest that STX8 mediates
      the recycling of CLDN16 and constitutes an important component of the CLDN16
      trafficking machinery in the kidney. 

PMID- 24659782
TI  - Transcription of angiogenin and ribonuclease 4 is regulated by RNA polymerase III
      elements and a CCCTC binding factor (CTCF)-dependent intragenic chromatin loop.
AB  - Angiogenin (ANG) and ribonuclease 4 (RNASE4), two members of the secreted and
      vertebrate-specific ribonuclease superfamily, play important roles in cancers and
      neurodegenerative diseases. The ANG and RNASE4 genes share genetic regions with
      promoter activities, but the structure and regulation of these putative promotes
      are unknown. We have characterized the promoter regions, defined the
      transcription start site, and identified a mechanism of transcription regulation
      that involves both RNA polymerase III (Pol III) elements and CCCTC binding factor
      (CTCF) sites. We found that two Pol III elements within the promoter region
      influence ANG and RNASE4 expression in a position- and orientation-dependent
      manner. We also provide evidence for the presence of an intragenic chromatin loop
      between the two CTCF binding sites located in two introns flanking the ANG coding
      exon. We found that formation of this intragenic loop preferentially enhances ANG
      transcription. These results suggest a multilayer transcriptional regulation of
      ANG and RNASE4 gene locus. These data also add more direct evidence to the notion
      that Pol III elements are able to directly influence Pol II gene transcription.
      Furthermore, our data indicate that a CTCF-dependent chromatin loop is able to
      differentially regulate transcription of genes that share the same promoters. 

PMID- 24659783
TI  - Mycobacterium tuberculosis phosphoenolpyruvate carboxykinase is regulated by
      redox mechanisms and interaction with thioredoxin.
AB  - Tuberculosis remains a major health concern worldwide. Eradication of its
      causative agent, the bacterial pathogen Mycobacterium tuberculosis, is
      particularly challenging due to a vast reservoir of latent carriers of the
      disease. Despite the misleading terminology of a so-called dormant state
      associated with latent infections, the bacteria have to maintain basic metabolic
      activities. Hypoxic conditions have been widely used as an in vitro system to
      study this dormancy. Such studies identified a rearrangement of central carbon
      metabolism to exploit fermentative processes caused by the lack of oxygen.
      Phosphoenolpyruvate carboxykinase (Pck; EC 4.1.1.32) is the enzyme at the center
      of these metabolic rearrangements. Although Pck is associated with
      gluconeogenesis under standard growth conditions, the enzyme can catalyze the
      reverse reaction, supporting anaplerosis of the tricarboxylic acid cycle, under
      conditions leading to slowed or stopped bacterial replication. To study the
      mechanisms that regulate the switch between two Pck functions, we systematically
      investigated factors influencing the gluconeogenic and anaplerotic reaction
      kinetics. We demonstrate that a reducing environment, as found under hypoxia
      triggered non-replicating conditions, accelerates the reaction in the anaplerotic
      direction. Furthermore, we identified proteins that interact with Pck. The
      interaction between Pck and the reduced form of mycobacterial thioredoxin, gene
      expression of which is increased under hypoxic conditions, also increased the Pck
      anaplerotic activity. We thus propose that a reducing environment and the protein
      protein interaction with thioredoxin in particular enable the Pck anaplerotic
      function under fermentative growth conditions. 

PMID- 24659784
TI  - Essential roles of neutral ceramidase and sphingosine in mitochondrial
      dysfunction due to traumatic brain injury.
AB  - In addition to immediate brain damage, traumatic brain injury (TBI) initiates a
      cascade of pathophysiological events producing secondary injury. The biochemical
      and cellular mechanisms that comprise secondary injury are not entirely
      understood. Herein, we report a substantial deregulation of cerebral sphingolipid
      metabolism in a mouse model of TBI. Sphingolipid profile analysis demonstrated
      increases in sphingomyelin species and sphingosine concurrently with up
      regulation of intermediates of de novo sphingolipid biosynthesis in the brain.
      Investigation of intracellular sites of sphingosine accumulation revealed an
      elevation of sphingosine in mitochondria due to the activation of neutral
      ceramidase (NCDase) and the reduced activity of sphingosine kinase 2 (SphK2). The
      lack of change in gene expression suggested that post-translational mechanisms
      are responsible for the shift in the activities of both enzymes.
      Immunoprecipitation studies revealed that SphK2 is complexed with NCDase and
      cytochrome oxidase (COX) subunit 1 in mitochondria and that brain injury hindered
      SphK2 association with the complex. Functional studies showed that sphingosine
      accumulation resulted in a decreased activity of COX, a rate-limiting enzyme of
      the mitochondrial electron transport chain. Knocking down NCDase reduced
      sphingosine accumulation in mitochondria and preserved COX activity after the
      brain injury. Also, NCDase knockdown improved brain function recovery and
      lessened brain contusion volume after trauma. These studies highlight a novel
      mechanism of secondary TBI involving a disturbance of sphingolipid-metabolizing
      enzymes in mitochondria and suggest a critical role for mitochondrial sphingosine
      in promoting brain injury after trauma. 

PMID- 24659786
TI  - Close bonding: the first report of TGF-beta and T cells.

PMID- 24659785
TI  - Noncanonical Gbeta Gib2 is a scaffolding protein promoting cAMP signaling through
      functions of Ras1 and Cac1 proteins in Cryptococcus neoformans.
AB  - Gbeta-like/RACK1 functions as a key mediator of various pathways and contributes
      to numerous cellular functions in eukaryotic organisms. In the pathogenic fungus
      Cryptococcus neoformans, noncanonical Gbeta Gib2 promotes cAMP signaling in cells
      lacking normal Gpa1 function while displaying versatility in interactions with
      Galpha Gpa1, protein kinase Pkc1, and endocytic intersectin Cin1. To elucidate
      the Gib2 functional mechanism(s), we demonstrate that Gib2 is required for normal
      growth and virulence. We show that Gib2 directly binds to Gpa1 and Ggamma
      Gpg1/Gpg2 and that it interacts with phosphodiesterase Pde2 and monomeric GTPase
      Ras1. Pde2 remains functionally dispensable, but Ras1 is found to associate with
      adenylyl cyclase Cac1 through the conserved Ras association domain. In addition,
      the ras1 mutant exhibits normal capsule formation, whereas the ras1 gpa1 mutant
      displays enhanced capsule formation, and the ras1 gpa1 cac1 mutant is acapsular.
      Collectively, these findings suggest that Gib2 promotes cAMP levels by relieving
      an inhibitory function of Ras1 on Cac1 in the absence of Gpa1. In addition, using
      GST affinity purification combined with mass spectrometry, we identified 47
      additional proteins that interact with Gib2. These proteins have putative
      functions ranging from signal transduction, energy generation, metabolism, and
      stress response to ribosomal function. After establishing and validating a
      protein-protein interactive network, we believe Gib2 to be a key
      adaptor/scaffolding protein that drives the formation of various protein
      complexes required for growth and virulence. Our study reveals Gib2 as an
      essential component in deciphering the complexity of regulatory networks that
      control growth and virulence in C. neoformans. 

PMID- 24659787
TI  - Pillars Article: production of transforming growth factor beta by human T
      lymphocytes and its potential role in the regulation of T cell growth. J Exp Med.
      1986. 163: 1037-1050.

PMID- 24659788
TI  - Modulation of T cell and innate immune responses by retinoic Acid.
AB  - Retinoic acid (RA) is produced by a number of cell types, including macrophages
      and dendritic cells, which express retinal dehydrogenases that convert vitamin A
      to its main biologically active metabolite, all-trans RA. All-trans RA binds to
      its nuclear retinoic acid receptors that are expressed in lymphoid cells and act
      as transcription factors to regulate cell homing and differentiation. RA
      production by CD103(+) dendritic cells and alveolar macrophages functions with
      TGF-beta to promote conversion of naive T cells into Foxp3(+) regulatory T cells
      and, thereby, maintain mucosal tolerance. Furthermore, RA inhibits the
      differentiation of naive T cells into Th17 cells. However, Th1 and Th17 responses
      are constrained during vitamin A deficiency and in nuclear RA receptor alpha
      defective mice. Furthermore, RA promotes effector T cell responses during
      infection or autoimmune diseases. Thus, RA plays a role in immune homeostasis in
      the steady-state but activates pathogenic T cells in conditions of inflammation. 

PMID- 24659789
TI  - At the bench: adoptive cell therapy for melanoma.
AB  - The cellular and molecular principles that furnish the foundation for ACT of
      melanoma and their implications for further clinical research are reviewed. The
      parallel advances in basic immunology, preclinical animal studies, and clinical
      trials over the last two decades have been integrated successfully with
      improvements in technology to produce an effective ACT strategy for patients with
      melanoma. From the initial observation that tumors could be treated effectively
      by the transfer of immune cells to current strategies using preconditioning with
      myeloablative therapy before adoptive transfer of native or genetically altered T
      cells, the role of preclinical animal models is discussed. The importance of the
      pmel transgenic mouse model in the determination of the mechanisms of
      lymphodepletion, the ongoing work to identify the optimal T cells for adoptive
      immunotherapy, and the early impact of the emerging discipline of synthetic
      biology are highlighted. The clinical consequences of the research described
      herein are reviewed in the companion manuscript. 

PMID- 24659790
TI  - Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3
      regulates proinflammatory TNF-alpha responses.
AB  - TNF-alpha is a proinflammatory cytokine, dramatically elevated during pathogenic
      infection and often responsible for inflammation-induced disease pathology. SOCS
      proteins are inhibitors of cytokine signaling and regulators of inflammation. In
      this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF
      alpha and negatively regulate its NF-kappaB-mediated signal transduction. We
      discovered that PBMCs from HCV-infected patients have elevated endogenous SOCS3
      expression but less TNF-alpha-mediated IkappaB degradation and proinflammatory
      cytokine production than healthy controls. HCV protein expression in Huh7
      hepatocytes also induced SOCS3 and directly inhibited TNF-alpha-mediated IL-8
      production. Furthermore, we found that SOCS3 associates with TRAF2 and inhibits
      TRAF2-mediated NF-kappaB promoter activity, suggesting a mechanism by which SOCS3
      inhibits TNF-alpha-mediated signaling. These results demonstrate a role for SOCS3
      in regulating proinflammatory TNF-alpha signal transduction and reveal a novel
      immune-modulatory mechanism by which HCV suppresses inflammatory responses in
      primary immune cells and hepatocytes, perhaps explaining mild pathology often
      associated with acute HCV infection. 

PMID- 24659791
TI  - RE: A model too far.

PMID- 24659792
TI  - Response.

PMID- 24659793
TI  - Progression of cognitive impairment in stroke/TIA patients over 3 years.
AB  - OBJECTIVES: To examine how cognitive deficits progress in the years following a
      stroke or transient ischaemic attack (TIA). METHODS: A follow-up study, with
      neuropsychological and MRI assessments undertaken 3 years after baseline
      assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy
      controls participating in the Sydney Stroke Study. Additional measures included
      cardiovascular risk factors and apolipoprotein E (APOE) genotype. RESULTS:
      Stroke/TIA patients had poorer cognitive function and more vascular risk factors
      than controls at baseline, but did not show greater decline in cognitive function
      over 3 years except for verbal memory. Patients with a subsequent stroke/TIA
      showed greater decline in global cognitive function and a number of domains.
      Rates of incident dementia were 5.9% per year in patients and 0.4% in controls.
      Both groups showed increased atrophy of the hippocampus, amygdala and whole
      brain, and an increase in white matter hyperintensities over 3 years; whole brain
      atrophy was greater in patients. Cognitive decline was greater in women and in
      those with smaller hippocampi at baseline. For patients without a subsequent
      stroke/TIA, those with smaller hippocampi or the APOE epsilon4 allele had greater
      global cognitive and verbal memory decline. CONCLUSIONS: In poststroke patients,
      cognitive decline was not greater than in comparison subjects, except for verbal
      memory, unless they had another stroke/TIA. However, dementia incidence was
      higher in patients, as might be expected from their poorer baseline cognitive
      functioning. Smaller hippocampi were associated with an increased risk of decline
      in memory, and APOE epsilon4 was a risk factor in those without a subsequent
      stroke/TIA.

PMID- 24659794
TI  - Natalizumab in clinical practice: managing the risks, enjoying the benefits.

PMID- 24659795
TI  - Is overwork weakness relevant in Charcot-Marie-Tooth disease?
AB  - BACKGROUND: In overwork weakness (OW), muscles are increasingly weakened by
      exercise, work or daily activities. Although it is a well-established phenomenon
      in several neuromuscular disorders, it is debated whether it occurs in Charcot
      Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than
      non-dominant and therefore if OW occurs we would expect them to become weaker.
      Four previous studies, comparing dominant and non-dominant hand strength in CMT
      series employing manual testing or myometry, gave contradictory results.
      Moreover, none of them examined the behaviour of lower limb muscles. METHODS: We
      tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral
      intrinsic hand and leg muscle strength with manual testing as well as manual
      dexterity. RESULTS: We found no significant difference between sides for the
      strength of first dorsal interosseous, abductor pollicis brevis, anterior
      tibialis and triceps surae. Dominant side muscles did not become weaker than non
      dominant with increasing age and disease severity (assessed with the CMT
      Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than
      the non-dominant with increasing age and disease severity. DISCUSSION: Our data
      does not support the OW hypothesis and the consequent harmful effect of exercise
      in patients with CMT1A. Physical activity should be encouraged, and
      rehabilitation remains the most effective treatment for CMT patients.

PMID- 24659796
TI  - Isolated limb dystonia as presenting feature of Parkin disease.

PMID- 24659798
TI  - Are more sphingosine 1-phosphate receptor agonists a better therapeutic option
      against multiple sclerosis?

PMID- 24659797
TI  - Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II
      trial.
AB  - OBJECTIVE: This double-blind, placebo-controlled, dose-finding phase IIb study
      evaluated the efficacy and safety of ponesimod, an oral selective S1P1 receptor
      modulator, for the treatment of patients with relapsing-remitting multiple
      sclerosis (RRMS). METHODS: 464 patients were randomised to receive once-daily
      oral ponesimod 10, 20 or 40 mg, or placebo for 24 weeks. The primary endpoint was
      the cumulative number of new T1 gadolinium-enhanced (T1 Gd+) lesions per patient
      recorded every 4 weeks from weeks 12 to 24 after study drug initiation. Secondary
      endpoints were the annualised confirmed relapse rate (ARR) and time to first
      confirmed relapse. Safety and tolerability were also evaluated. RESULTS: The mean
      cumulative number of new T1 Gd+ lesions at weeks 12-24 was significantly lower in
      the ponesimod 10 mg (3.5; rate ratio (RR) 0.57; p=0.0318), 20 mg (1.1; RR 0.17;
      p<0.0001) and 40 mg (1.4; RR 0.23; p<0.0001) groups compared with placebo (6.2).
      The mean ARR was lower with 40 mg ponesimod versus placebo, with a maximum
      reduction of 52% (0.25 vs 0.53; p=0.0363). The time to first confirmed relapse
      was increased with ponesimod compared with placebo. The proportion of patients
      with >= 1 treatment-emergent adverse events (AEs) was similar across ponesimod
      groups and the placebo group. Frequently reported AEs with higher incidence in
      the three ponesimod groups compared with placebo were anxiety, dizziness,
      dyspnoea, increased alanine aminotransferase, influenza, insomnia and peripheral
      oedema. CONCLUSIONS: Once-daily treatment with ponesimod 10, 20 or 40 mg
      significantly reduced the number of new T1 Gd+ lesions and showed a beneficial
      effect on clinical endpoints. Ponesimod was generally well tolerated, and further
      investigation of ponesimod for the treatment of RRMS is under consideration.
      TRIAL REGISTRATION NUMBER: NCT01006265.

PMID- 24659799
TI  - Rab5 is required in metastatic cancer cells for Caveolin-1-enhanced Rac1
      activation, migration and invasion.
AB  - Rab5 is a small GTPase that regulates early endosome trafficking and other
      cellular processes, including cell adhesion and migration. Specifically, Rab5
      promotes Rac1 activation and cancer cell migration, but little is known about the
      upstream regulators of Rab5. We have previously shown that the scaffolding
      protein Caveolin-1 (CAV1) promotes Rac1 activation and migration of cancer cells.
      Here, we hypothesized that CAV1 stimulates Rab5 activation, leading to increased
      Rac1 activity and cell migration. Expression of CAV1 in B16-F10 mouse melanoma
      and HT-29(US) human colon adenocarcinoma cells increased the GTP loading of Rab5,
      whereas shRNA-mediated targeting of endogenous CAV1 in MDA-MB-231 breast cancer
      cells decreased Rab5-GTP levels. Accordingly, shRNA-mediated downregulation of
      Rab5 decreased CAV1-mediated Rac1 activation, cell migration and invasion in B16
      F10 and HT-29(US) cells. Expression of CAV1 was accompanied by increased
      recruitment of Tiam1, a Rac1 guanine nucleotide exchange factor (GEF), to Rab5
      positive early endosomes. Using the inhibitor NSC23766, Tiam1 was shown to be
      required for Rac1 activation and cell migration induced by CAV1 and Rab5.
      Mechanistically, we provide evidence implicating p85alpha (also known as PIK3R1),
      a Rab5 GTPase-activating protein (GAP), in CAV1-dependent effects, by showing
      that CAV1 recruits p85alpha, precluding p85alpha-mediated Rab5 inactivation and
      increasing cell migration. In summary, these studies identify a novel CAV1-Rab5
      Rac1 signaling axis, whereby CAV1 prevents Rab5 inactivation, leading to
      increased Rac1 activity and enhanced tumor cell migration and invasion. 

PMID- 24659800
TI  - IPS-1 plays an essential role in dsRNA-induced stress granule formation by
      interacting with PKR and promoting its activation.
AB  - The formation of cytoplasmic stress granules and the innate immune response are
      two distinct cellular stress responses. Our study investigated the involvement of
      four innate immune proteins - retinoic-acid-inducible gene I (RIG-I, also known
      as DDX58), melanoma differentiation-associated gene 5 (MDA5, also known as
      IFIH1), IFN-beta promoter stimulator (IPS-1, also known as MAVS) and protein
      kinase regulated by dsRNA (PKR, also known as EIF2AK2) in the formation of stress
      granules. Knockdown of IPS-1 or PKR significantly decreased the formation of
      stress granules induced by double-stranded (ds)RNA. IPS-1 depletion markedly
      attenuated the phosphorylation of PKR and eIF2alpha that was triggered by dsRNA,
      and IPS-1 facilitated the in vitro autophosphorylation of PKR. In IPS-1-depleted
      cells, the dsRNA-mediated dimerization of PKR through its dsRNA-binding domains
      was significantly abrogated, suggesting that IPS-1 might be involved in PKR
      dimerization. By co-immunoprecipitation and pulldown assays, our data demonstrate
      that IPS-1 directly binds to PKR through the IPS-1 caspase activation and
      recruitment domain (CARD), suggesting that the effect of IPS-1 on the formation
      of stress granules might be exerted through interacting with PKR and mediating
      its activation. PKR was recruited into stress granules upon activation, whereas
      the majority of IPS-1 protein formed clusters on mitochondrial membranes. Our
      work provides the first evidence that the innate signaling molecule IPS-1 plays
      an essential role in stress granule formation. 

PMID- 24659801
TI  - An RNAi screen identifies KIF15 as a novel regulator of the endocytic trafficking
      of integrin.
AB  - alpha2beta1 integrin is one of the most important collagen-binding receptors, and
      it has been implicated in numerous thrombotic and immune diseases. alpha2beta1
      integrin is a potent tumour suppressor, and its downregulation is associated with
      increased metastasis and poor prognosis in breast cancer. Currently, very little
      is known about the mechanism that regulates the cell-surface expression and
      trafficking of alpha2beta1 integrin. Here, using a quantitative fluorescence
      microscopy-based RNAi assay, we investigated the impact of 386 cytoskeleton
      associated or -regulatory genes on alpha2 integrin endocytosis and found that 122
      of these affected the intracellular accumulation of alpha2 integrin. Of these, 83
      were found to be putative regulators of alpha2 integrin trafficking and/or
      expression, with no observed effect on the internalization of epidermal growth
      factor (EGF) or transferrin. Further interrogation and validation of the siRNA
      screen revealed a role for KIF15, a microtubule-based molecular motor, as a
      significant inhibitor of the endocytic trafficking of alpha2 integrin. Our data
      suggest a novel role for KIF15 in mediating plasma membrane localization of the
      alternative clathrin adaptor Dab2, thus impinging on pathways that regulate
      alpha2 integrin internalization. 

PMID- 24659802
TI  - P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin
      polarity in neutrophils.
AB  - G-protein-coupled receptors (GPCRs) regulate the organisation of the actin
      cytoskeleton by activating the Rac subfamily of small GTPases. The guanine
      nucleotide-exchange factor (GEF) P-Rex1 is engaged downstream of GPCRs and
      phosphoinositide 3-kinase (PI3K) in many cell types, and promotes tumorigenic
      signalling and metastasis in breast cancer and melanoma, respectively. Although P
      Rex1-dependent functions have been attributed to its GEF activity towards Rac1,
      we show that P-Rex1 also acts as a GEF for the Rac-related GTPase RhoG, both in
      vitro and in GPCR-stimulated primary mouse neutrophils. Furthermore, loss of
      either P-Rex1 or RhoG caused equivalent reductions in GPCR-driven Rac activation
      and Rac-dependent NADPH oxidase activity, suggesting they both function upstream
      of Rac in this system. Loss of RhoG also impaired GPCR-driven recruitment of the
      Rac GEF DOCK2, and F-actin, to the leading edge of migrating neutrophils. Taken
      together, our results reveal a new signalling hierarchy in which P-Rex1, acting
      as a GEF for RhoG, regulates Rac-dependent functions indirectly through RhoG
      dependent recruitment of DOCK2. These findings thus have broad implications for
      our understanding of GPCR signalling to Rho GTPases and the actin cytoskeleton. 

PMID- 24659804
TI  - Formation of adherens junctions leads to the emergence of a tissue-level tension
      in epithelial monolayers.
AB  - Adherens junctions and desmosomes integrate the cytoskeletons of adjacent cells
      into a mechanical syncitium. In doing so, intercellular junctions endow tissues
      with the strength needed to withstand the mechanical stresses encountered in
      normal physiology and to coordinate tension during morphogenesis. Though much is
      known about the biological mechanisms underlying junction formation, little is
      known about how tissue-scale mechanical properties are established. Here, we use
      deep atomic force microscopy (AFM) indentation to measure the apparent stiffness
      of epithelial monolayers reforming from dissociated cells and examine which
      cellular processes give rise to tissue-scale mechanics. We show that the
      formation of intercellular junctions coincided with an increase in the apparent
      stiffness of reforming monolayers that reflected the generation of a tissue-level
      tension. Tension rapidly increased, reaching a maximum after 150 min, before
      settling to a lower level over the next 3 h as monolayers established
      homeostasis. The emergence of tissue tension correlated with the formation of
      adherens junctions but not desmosomes. As a consequence, inhibition of any of the
      molecular mechanisms participating in adherens junction initiation, remodelling
      and maturation significantly impeded the emergence of tissue-level tension in
      monolayers. 

PMID- 24659805
TI  - A real-time method for measuring cAMP production modulated by Galphai/o-coupled
      metabotropic glutamate receptors.
AB  - Group II and group III metabotropic glutamate (mGlu) receptors are G protein
      coupled receptors (GPCRs) that inhibit adenylyl cyclase via activation of
      Galphai/o. The purpose of this study was to design a universal method that
      overcomes previous challenges in consistently measuring group II and group III
      mGlu-receptor (mGluR) activation in stably transfected systems. In Chinese
      hamster ovary (CHO) cells stably transfected with the GloSensor cAMP biosensor,
      we optimized conditions for simple and highly reproducible (<5% S.E.M.)
      measurements of cAMP in real time. The GloSensor cAMP biosensor is a recombinant
      firefly luciferase conjugated to a cAMP-binding domain, where cAMP binding
      promotes a conformational shift within the GloSensor protein, inducing luciferase
      activity; cAMP levels are positively correlated with light output resulting from
      the luciferase-mediated breakdown of d-luciferin. Each group II and group III
      mGluR was then stably transfected into the CHO-GloSensor cell line, and
      experimental conditions were optimized for each receptor. During assay
      optimization, we observed ion sensitivity of several receptors and inverse
      agonist activity of the antagonist, LY341495 [2-[(1S,2S)-2-carboxycyclopropyl]-3
      (9H-xanthen-9-yl)-d-alanine]. Although these phenomena have been previously
      reported, they remain poorly understood, emphasizing the GloSensor assay as an
      important tool with which to study group II and group III mGlu receptors. Our
      results highlight many advantages of using the GloSensor method for measuring
      activation of group II and group III mGlu receptors, and they further suggest
      that corresponding methods designed to measure activation of any Galphai/o- or
      Galphas-coupled GPCR will be similarly advantageous. 

PMID- 24659803
TI  - Regulation of Cop9 signalosome activity by the EF-hand Ca2+-binding protein
      tescalcin.
AB  - The Ca(2+)-binding protein tescalcin is known to be involved in hematopoietic
      cell differentiation; however, this mechanism is poorly understood. Here, we
      identify CSN4 (subunit 4 of the COP9 signalosome) as a novel binding partner of
      tescalcin. The COP9 signalosome (CSN) is a multiprotein complex that is essential
      for development in all eukaryotes. This interaction is selective, Ca(2+)
      dependent and involves the PCI domain of CSN4 subunit. We then investigated
      tescalcin and CSN activity in human erythroleukemia HEL and promyelocytic
      leukemia K562 cells and find that phorbol 12-myristate 13-acetate (PMA)-induced
      differentiation, resulting in the upregulation of tescalcin, coincides with
      reduced deneddylation of cullin-1 (Cul1) and stabilization of p27(Kip1) -
      molecular events that are associated with CSN activity. The knockdown of
      tescalcin led to an increase in Cul1 deneddylation, expression of F-box protein
      Skp2 and the transcription factor c-Jun, whereas the levels of cell cycle
      regulators p27(Kip1) and p53 decreased. These effects are consistent with the
      hypothesis that tescalcin might play a role as a negative regulator of CSN
      activity towards Cul1 in the process of induced cell differentiation. 

PMID- 24659806
TI  - Bryostatin-1 restores hippocampal synapses and spatial learning and memory in
      adult fragile x mice.
AB  - Fragile X syndrome (FXS) is caused by transcriptional silencing in neurons of the
      FMR1 gene product, fragile X mental retardation protein (FMRP), a repressor of
      dendritic mRNA translation. The lack of FMRP leads to dysregulation of
      synaptically driven protein synthesis and impairments of intellect, cognition,
      and behavior, a disorder that currently has no effective therapeutics. Fragile X
      mice were treated with chronic bryostatin-1, a relatively selective protein
      kinase epsilon activator with pharmacological profiles of rapid mGluR
      desensitization, synaptogenesis, and synaptic maturation/repairing. Differences
      in the major FXS phenotypes, synapses, and cognitive functions were evaluated and
      compared among the age-matched groups. Long-term treatment with bryostatin-1
      rescues adult fragile X mice from the disorder phenotypes, including
      normalization of most FXS abnormalities in hippocampal brain-derived neurotrophic
      factor expression and secretion, postsynaptic density-95 levels, glycogen
      synthase kinase-3beta phosphorylation, transformation of immature dendritic
      spines to mature synapses, densities of the presynaptic and postsynaptic
      membranes, and spatial learning and memory. Our results show that synaptic and
      cognitive function of adult FXS mice can be normalized through pharmacologic
      treatment and that bryostatin-1-like agents may represent a novel class of drugs
      to treat fragile X mental retardation even after postpartum brain development has
      largely completed. 

PMID- 24659807
TI  - Increase in cell motility by carbon ion irradiation via the Rho signaling pathway
      and its inhibition by the ROCK inhibitor Y-27632 in lung adenocarcinoma A549
      cells.
AB  - This study aimed to investigate the effect of carbon ion (C-ion) irradiation on
      cell motility through the ras homolog gene family member (Rho) signaling pathway
      in the human lung adenocarcinoma cell line A549. Cell motility was assessed by a
      wound-healing assay, and the formation of cell protrusions was evaluated by F
      actin staining. Cell viability was examined by the WST-1 assay. The expression of
      myosin light chain 2 (MLC2) and the phosphorylation of MLC2 at Ser19 (P-MLC2-S19)
      were analyzed by Western blot. At 48 h after irradiation, the wound-healing assay
      demonstrated that migration was significantly greater in cells irradiated with C
      ion (2 or 8 Gy) than in unirradiated cells. Similarly, F-actin staining showed
      that the formation of protrusions was significantly increased in cells irradiated
      with C-ion (2 or 8 Gy) compared with unirradiated cells. The observed increase in
      cell motility due to C-ion irradiation was similar to that observed due to X-ray
      irradiation. Western-blot analysis showed that C-ion irradiation (8 Gy) increased
      P-MLC2-S19 expression compared with in unirradiated controls, while total MLC2
      expression was unchanged. Exposure to a non-toxic concentration of Y-27632, a
      specific inhibitor of Rho-associated coiled-coil-forming protein kinase (ROCK),
      reduced the expression of P-MLC2-S19 after C-ion irradiation (8 Gy), resulting in
      a significant reduction in migration. These data suggest that C-ion irradiation
      increases cell motility in A549 cells via the Rho signaling pathway and that ROCK
      inhibition reduces that effect.

PMID- 24659810
TI  - High frequency of cultivable human subgroup F adenoviruses in stool samples from
      a paediatric population admitted to hospital with acute gastroenteritis.
AB  - The family Adenoviridae consists of five genera of which the genus Mastadenovirus
      includes human viruses classified into 57 serotypes clustered into seven
      subgroups (A-G). Serotypes 40 and 41 (subgroup F) are specifically associated
      with childhood gastroenteritis and are the most common cause of acute
      gastroenteritis in young children after rotaviruses and noroviruses. Standard
      methods for laboratory diagnosis of adenovirus infection include electron
      microscopy (EM) and conventional cell culture (CCC), although it is widely
      considered that adenoviruses 40 and 41 are difficult to cultivate, such that
      their circulation is most likely underestimated. One hundred and ten faecal
      specimens from paediatric patients with gastroenteritis were confirmed positive
      for adenovirus by EM and/or CCC at the Virology Unit of the University Hospital
      of Parma, Italy, during the period January 2010-December 2012. They were analysed
      to determine the actual prevalence of adenovirus 40 and 41 in these patients
      using PCR and restriction endonuclease analysis, and to evaluate their ability to
      be cultivated in standard cell lines. The results showed a high prevalence of
      subgroup F (62.7 %), with serotype 41 (89.8 %) predominating over serotype 40
      (10.2 %). Surprisingly, among the 75 adenoviruses isolated by CCC, 37 (49 %)
      belonged to subgroup F, suggesting a higher capacity of adenovirus 40 and 41 to
      replicate in cell culture than previously thought. PCR and restriction enzyme
      techniques provide an efficient means of diagnosing enteric adenoviruses
      correctly, including subgroup F adenovirus strains in young children with
      gastroenteritis.

PMID- 24659814
TI  - Evidence for selection on gene expression in cultivated rice (Oryza sativa).
AB  - Artificial selection has been used throughout plant domestication and breeding to
      develop crops that are adapted to diverse environments. Here, we investigate
      whether gene regulatory changes have been widespread targets of lineage-specific
      selection in cultivated lines Minghui 63 and Zhenshan 97 of rice, Oryza sativa. A
      line experiencing positive selection for either an increase or a decrease in
      genes' transcript abundances is expected to have an overabundance of expression
      quantitative trait locus (eQTL) alleles that increase or decrease those genes'
      expression, respectively. Results indicate that several genes that share Gene
      Ontology terms or are members of the same coexpression module have eQTL alleles
      from one parent that consistently increase gene expression relative to the second
      parent. A second line of evidence for lineage-specific selection is an
      overabundance of cis-trans pairs of eQTL alleles that affect gene expression in
      the same direction (are reinforcing). Across all cis-trans pairs of eQTL,
      including pairs that both weakly and strongly affect gene expression, there is no
      evidence for selection. However, the frequency of genes with reinforcing eQTL
      increases with eQTL strength. Therefore, there is evidence that eQTL with strong
      effects were positively selected during rice cultivation. Among 41 cis-trans
      pairs with strong trans eQTL, 31 have reinforcing eQTL. Several of the candidate
      genes under positive selection accurately predict phenotypic differences between
      Minghui 63 and Zhenshan 97. Overall, our results suggest that positive selection
      for regulatory alleles may be a key factor in plant improvement. 

PMID- 24659815
TI  - High fitness costs and instability of gene duplications reduce rates of evolution
      of new genes by duplication-divergence mechanisms.
AB  - An important mechanism for generation of new genes is by duplication-divergence
      of existing genes. Duplication-divergence includes several different submodels,
      such as subfunctionalization where after accumulation of neutral mutations the
      original function is distributed between two partially functional and
      complementary genes, and neofunctionalization where a new function evolves in one
      of the duplicated copies while the old function is maintained in another copy.
      The likelihood of these mechanisms depends on the longevity of the duplicated
      state, which in turn depends on the fitness cost and genetic stability of the
      duplications. Here, we determined the fitness cost and stability of defined gene
      duplications/amplifications on a low copy number plasmid. Our experimental
      results show that the costs of carrying extra gene copies are substantial and
      that each additional kilo base pairs of DNA reduces fitness by approximately
      0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate
      to lower copy numbers in absence of selection. Mathematical modeling shows that
      the fitness costs and instability strongly reduces the likelihood of both sub-
      and neofunctionalization, but that these effects can be offset by positive
      selection for novel beneficial functions. 

PMID- 24659820
TI  - Epithelial-to-mesenchymal transition mediates docetaxel resistance and high risk
      of relapse in prostate cancer.
AB  - Molecular characterization of radical prostatectomy specimens after systemic
      therapy may identify a gene expression profile for resistance to therapy. This
      study assessed tumor cells from patients with prostate cancer participating in a
      phase II neoadjuvant docetaxel and androgen deprivation trial to identify
      mediators of resistance. Transcriptional level of 93 genes from a docetaxel
      resistant prostate cancer cell lines microarray study was analyzed by TaqMan low
      density arrays in tumors from patients with high-risk localized prostate cancer
      (36 surgically treated, 28 with neoadjuvant docetaxel + androgen deprivation).
      Gene expression was compared between groups and correlated with clinical outcome.
      VIM, AR and RELA were validated by immunohistochemistry. CD44 and ZEB1 expression
      was tested by immunofluorescence in cells and tumor samples. Parental and
      docetaxel-resistant castration-resistant prostate cancer cell lines were tested
      for epithelial-to-mesenchymal transition (EMT) markers before and after docetaxel
      exposure. Reversion of EMT phenotype was investigated as a docetaxel resistance
      reversion strategy. Expression of 63 (67.7%) genes differed between groups (P <
      0.05), including genes related to androgen receptor, NF-kappaB transcription
      factor, and EMT. Increased expression of EMT markers correlated with radiologic
      relapse. Docetaxel-resistant cells had increased EMT and stem-like cell markers
      expression. ZEB1 siRNA transfection reverted docetaxel resistance and reduced
      CD44 expression in DU-145R and PC-3R. Before docetaxel exposure, a selected
      CD44(+) subpopulation of PC-3 cells exhibited EMT phenotype and intrinsic
      docetaxel resistance; ZEB1/CD44(+) subpopulations were found in tumor cell lines
      and primary tumors; this correlated with aggressive clinical behavior. This study
      identifies genes potentially related to chemotherapy resistance and supports
      evidence of the EMT role in docetaxel resistance and adverse clinical behavior in
      early prostate cancer.

PMID- 24659821
TI  - PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3)
      and CXCR4-mediated microenvironmental interactions (PIM1).
AB  - Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic
      leukemia (CLL) and is important for CLL cell survival, migration, and interaction
      with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1
      was shown to regulate the surface expression of the CXCR4 receptor. Here, we show
      that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1
      3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339
      in CLL compared with normal lymphocytes. Furthermore, CXCR4 phosphorylation
      correlates with PIM1 protein expression and PIM1 transcript levels in CLL. PIM
      kinase inhibition with three different PIM kinase inhibitors induced apoptosis in
      CLL cells independent of the presence of protective stromal cells. In addition,
      PIM inhibition caused dephosphorylation of the CXCR4 receptor on Ser339,
      resulting in enhanced ligand-dependent CXCR4 internalization and reduced re
      externalization after withdrawal of CXCL12. Furthermore, PIM inhibition in CLL
      cells blocked CXCR4 functions, such as migration toward CXCL12- or CXCL12-induced
      extracellular signal-regulated kinase (ERK) phosphorylation. In concordance,
      pretreatment of CLL cells with PIM kinase inhibitors strongly reduced homing of
      CLL cells toward the bone marrow and the spleen of Rag2(-/-)gammac(-/-) mice in
      vivo. Interestingly, the knockdown of PIM kinases in CLL cells demonstrated
      diverging functions, with PIM1 regulating CXCR4 surface expression and PIM2 and
      PIM3 as important for the survival of CLL cells. Our results show that PIM kinase
      inhibitors are an effective therapeutic option for CLL, not only by impairing
      PIM2/3-mediated CLL cell survival, but also by blocking the PIM1/CXCR4-mediated
      interaction of CLL cells with their protective microenvironment.

PMID- 24659822
TI  - Creation and Evaluation of a Single-chain Antibody Tetramer that Targets Brain
      Endothelial Cells.
AB  - Antibodies that target and internalize into blood-brain barrier (BBB) endothelial
      cells offer promise as drug delivery agents. Previously, we identified a single
      chain antibody (scFvA) capable of binding to the BBB. In an attempt to improve
      the binding and internalization properties of the single chain antibody (scFvA),
      a biotinylation tag (Avitag) was fused to scFvA and the protein secreted by
      yeast. The scFvA-Avitag could be biotinylated by yeast-displayed BirA enzyme and
      biotinylated scFvA-Avitag could be used to create scFv tetramers. Tetramerization
      of scFvA improved the internalization of scFvA into BBB endothelial cells, and
      biotinylated scFvA-Avitag could also be used to target streptavidin-coated
      quantum dots for BBB endothelial cell internalization. Perfusing the rat brain
      with scFvA-tetramer confirmed that the antigen targeted by scFvA is distributed
      on blood side of the BBB, suggesting the potential for downstream application of
      scFvA in brain-targeted drug delivery.

PMID- 24659823
TI  - A cost-efficient frequency-domain photoacoustic imaging system.
AB  - Photoacoustic (PA) imaging techniques have recently attracted much attention and
      can be used for noninvasive imaging of biological tissues. Most PA imaging
      systems in research laboratories use the time domain method with expensive
      nanosecond pulsed lasers that are not affordable for most educational
      laboratories. Using an intensity modulated light source to excite PA signals is
      an alternative technique, known as the frequency domain method, with a much lower
      cost. In this paper, we describe a simple frequency domain PA system and
      demonstrate its imaging capability. The system provides opportunities not only to
      observe PA signals in tissue phantoms, but also to acquire hands-on skills in PA
      signal detection. It also provides opportunities to explore the underlying
      mechanisms of the PA effect.

PMID- 24659824
TI  - Role of Grooming in Reducing Tick Load in Wild Baboons (Papio cynocephalus).
AB  - Nonhuman primate species spend a conspicuous amount of time grooming during
      social interactions, a behavior that probably serves both social and health
      related functions. While the social implications of grooming have been relatively
      well studied, less attention has been paid to the health benefits, especially the
      removal of ectoparasites, which may act as vectors in disease transmission. In
      this study, we examined the relationship between grooming behavior, tick load
      (number of ticks), and haemoprotozoan infection status in a population of wild
      free-ranging baboons (Papio cynocephalus). We found that the amount of grooming
      received was influenced by an individual's age, sex and dominance rank. The
      amount of grooming received, in turn, affected the tick load of an individual.
      Baboons with higher tick loads had lower packed red cell volume (PCV or
      haematocrit), one general measure of health status. We detected a tick-borne
      haemoprotozoan, Babesia microti, but its low prevalence in the population
      precluded identifying sources of variance in infection.

PMID- 24659825
TI  - Spatio-temporal Genetic Structure of a Tropical Bee Species Suggests High
      Dispersal Over a Fragmented Landscape.
AB  - Habitat destruction threatens biodiversity by reducing the amount of available
      resources and connectivity among geographic areas. For organisms living in
      fragmented habitats, population persistence may depend on dispersal, which
      maintains gene flow among fragments and can prevent inbreeding within them. It is
      centrally important to understand patterns of dispersal for bees living in
      fragmented areas given the importance of pollination systems and recently
      documented declines in bee populations. We used population and landscape genetic
      techniques to characterize patterns of dispersal over a large fragmented area in
      southern Costa Rica for the orchid bee species Euglossa championi. First, we
      estimated levels of genetic differentiation among forest fragments as phipt, an
      analog to the traditional summary statistic Fst, as well as two statistics that
      may more adequately represent levels of differentiation, G'st and Dest . Second,
      we used a Bayesian approach to determine the number and composition of genetic
      groups in our sample. Third we investigated how genetic differentiation changes
      with distance. Fourth, we determined the extent to which deforested areas
      restrict dispersal. Finally, we estimated the extent to which there were temporal
      differences in allele frequencies within the same forest fragments. Within years
      we found low levels of differentiation even over 80 km, and no effect of land use
      type on level of genetic differentiation. However, we found significant genetic
      differentiation between years. Taken together our results suggest that there are
      high levels of gene flow over this geographic area, and that individuals show low
      site fidelity over time.

PMID- 24659826
TI  - Does Leisure Time as a Stress Coping Resource Increase Affective Complexity?
      Applying the Dynamic Model of Affect (DMA).
AB  - Affective complexity, a manifestation of psychological well-being, refers to the
      relative independence between positive and negative affect (PA, NA). According to
      the Dynamic Model of Affect (DMA), stressful situations lead to highly inverse PA
      NA relationship, reducing affective complexity. Meanwhile, positive events can
      sustain affective complexity by restoring PA-NA independence. Leisure, a type of
      positive events, has been identified as a coping resource. This study used the
      DMA to assess whether leisure time helps restore affective complexity on
      stressful days. We found that on days with more leisure time than usual, an
      individual experienced less negative PA-NA relationship after daily stressful
      events. The finding demonstrates the value of leisure time as a coping resource
      and the DMA's contribution to coping research.

PMID- 24659827
TI  - Estimating the Effects of Parental Divorce and Death With Fixed Effects Models.
AB  - The authors used child fixed effects models to estimate the effects of parental
      divorce and death on a variety of outcomes using 2 large national data sets: (a)
      the Early Childhood Longitudinal Study, Kindergarten Cohort (kindergarten through
      the 5th grade) and (b) the National Educational Longitudinal Study (8th grade to
      the senior year of high school). In both data sets, divorce and death were
      associated with multiple negative outcomes among children. Although evidence for
      a causal effect of divorce on children was reasonably strong, effect sizes were
      small in magnitude. A second analysis revealed a substantial degree of
      variability in children's outcomes following parental divorce, with some children
      declining, others improving, and most not changing at all. The estimated effects
      of divorce appeared to be strongest among children with the highest propensity to
      experience parental divorce.

PMID- 24659828
TI  - Single and Multiple Ability Estimation in the SEM Framework: A Non-Informative
      Bayesian Estimation Approach.
AB  - Latent variable models with many categorical items and multiple latent constructs
      result in many dimensions of numerical integration, and the traditional
      frequentist estimation approach, such as maximum likelihood (ML), tends to fail
      due to model complexity. In such cases, Bayesian estimation with diffuse priors
      can be used as a viable alternative to ML estimation. The present study compares
      the performance of Bayesian estimation to ML estimation in estimating single or
      multiple ability factors across two types of measurement models in the structural
      equation modeling framework: a multidimensional item response theory (MIRT) model
      and a multiple-indicator multiple-cause (MIMIC) model. A Monte Carlo simulation
      study demonstrates that Bayesian estimation with diffuse priors, under various
      conditions, produces quite comparable results to ML estimation in the single- and
      multi-level MIRT and MIMIC models. Additionally, an empirical example utilizing
      the Multistate Bar Examination is provided to compare the practical utility of
      the MIRT and MIMIC models. Structural relationships among the ability factors,
      covariates, and a binary outcome variable are investigated through the single-
      and multi-level measurement models. The paper concludes with a summary of the
      relative advantages of Bayesian estimation over ML estimation in MIRT and MIMIC
      models and suggests strategies for implementing these methods.

PMID- 24659829
TI  - UNIFORMLY MOST POWERFUL BAYESIAN TESTS.
AB  - Uniformly most powerful tests are statistical hypothesis tests that provide the
      greatest power against a fixed null hypothesis among all tests of a given size.
      In this article, the notion of uniformly most powerful tests is extended to the
      Bayesian setting by defining uniformly most powerful Bayesian tests to be tests
      that maximize the probability that the Bayes factor, in favor of the alternative
      hypothesis, exceeds a specified threshold. Like their classical counterpart,
      uniformly most powerful Bayesian tests are most easily defined in one-parameter
      exponential family models, although extensions outside of this class are
      possible. The connection between uniformly most powerful tests and uniformly most
      powerful Bayesian tests can be used to provide an approximate calibration between
      p-values and Bayes factors. Finally, issues regarding the strong dependence of
      resulting Bayes factors and p-values on sample size are discussed.

PMID- 24659830
TI  - Relations among Three Parametric Multiple Testing Methods for Correlated Tests.
AB  - Multiple endpoints in clinical trials are usually correlated. To control the
      family-wise type I error rate, both Huque and Alosh's flexible fixed-sequence
      (FFS) testing method and Li and Mehrotra's adaptive alpha allocation approach
      (4A) have taken into account correlations among endpoints. I suggested a weighted
      multiple testing correction (WMTC) for correlated tests and compared it with FFS.
      However, the relationship between the 4A method and the FFS method or the
      relationship between the 4A method and the WMTC method has not been studied. In
      this paper, simulations are conducted to investigate these relationships.
      Tentative guidelines to help choosing an appropriate method are provided.

PMID- 24659831
TI  - The Diagnosticity of Color for Emotional Objects.
AB  - Object classification can be facilitated if simple diagnostic features can be
      used to determine class membership. Previous studies have found that simple
      shapes may be diagnostic for emotional content and automatically alter the
      allocation of visual attention. In the present study, we analyzed whether color
      is diagnostic of emotional content and tested whether emotionally diagnostic hues
      alter the allocation of visual attention. Reddish-yellow hues are more common in
      (i.e., diagnostic of) emotional images, particularly images with positive
      emotional content. An exogenous cueing paradigm was employed to test whether
      these diagnostic hues orient attention differently from other hues due to the
      emotional diagnosticity. In two experiments, we found that participants allocated
      attention differently to diagnostic hues than to non-diagnostic hues, in a
      pattern indicating a broadening of spatial attention when cued with diagnostic
      hues. Moreover, the attentional broadening effect was predicted by self-reported
      measures of affective style, linking the behavioral effect to emotional
      processes. These results confirm the existence and use of diagnostic features for
      the rapid detection of emotional content.

PMID- 24659832
TI  - The Effects of Approach-Avoidance Modification on Social Anxiety Disorder: A
      Pilot Study.
AB  - Cognitive bias modification has recently been discussed as a possible
      intervention for mental disorders. A specific form of this novel treatment
      approach is approach-avoidance modification. In order to examine the efficacy of
      approach-avoidance modification for positive stimuli associated with social
      anxiety, we recruited 43 individuals with social anxiety disorder and randomly
      assigned them to a training (implicit training to approach smiling faces) or a
      control (equal approach and avoidance of smiling faces) condition in three
      sessions over the course of a one-week period. Dependent measures included
      clinician ratings, self-report measures of social anxiety, and overt behavior
      during behavioral approach tasks. No group differences in any of the outcome
      measures were observed after training. In addition, while individuals in the
      training group showed increased approach tendency in one of the sessions, this
      effect was inconsistent across the three sessions and did not result in long-term
      changes in implicit approach tendencies between the groups over the course of the
      entire study. These results suggest that approach-avoidance modification might
      result in short-lasting effects on implicit approach tendencies towards feared
      positive stimuli, but this modification may not result in meaningful behavioral
      change or symptom reduction in individuals with social anxiety disorder.

PMID- 24659833
TI  - Physiology and its importance for reference intervals.
AB  - Reference intervals are ideally defined on apparently healthy individuals and
      should be distinguished from clinical decision limits that are derived from known
      diseased patients. Knowledge of physiological changes is a prerequisite for
      understanding and developing reference intervals. Reference intervals may differ
      for various subpopulations because of differences in their physiology, most
      obviously between men and women, but also in childhood, pregnancy and the
      elderly. Changes in laboratory measurements may be due to various physiological
      factors starting at birth including weaning, the active toddler, immunological
      learning, puberty, pregnancy, menopause and ageing. The need to partition
      reference intervals is required when there are significant physiological changes
      that need to be recognised. It is important that laboratorians are aware of these
      changes otherwise reference intervals that attempt to cover a widened inter
      individual variability may lose their usefulness. It is virtually impossible for
      any laboratory to directly develop reference intervals for each of the
      physiological changes that are currently known, however indirect techniques can
      be used to develop or validate reference intervals in some difficult situations
      such as those for children. Physiology describes our life's journey, and it is
      only when we are familiar with that journey that we can appreciate a pathological
      departure. 

PMID- 24659835
TI  - Uncertainty in measurement: a review of monte carlo simulation using microsoft
      excel for the calculation of uncertainties through functional relationships,
      including uncertainties in empirically derived constants.
AB  - The Guide to the Expression of Uncertainty in Measurement (usually referred to as
      the GUM) provides the basic framework for evaluating uncertainty in measurement.
      The GUM however does not always provide clearly identifiable procedures suitable
      for medical laboratory applications, particularly when internal quality control
      (IQC) is used to derive most of the uncertainty estimates. The GUM modelling
      approach requires advanced mathematical skills for many of its procedures, but
      Monte Carlo simulation (MCS) can be used as an alternative for many medical
      laboratory applications. In particular, calculations for determining how
      uncertainties in the input quantities to a functional relationship propagate
      through to the output can be accomplished using a readily available spreadsheet
      such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo
      random numbers which are then forced to follow a prescribed probability
      distribution. When IQC data provide the uncertainty estimates the normal
      (Gaussian) distribution is generally considered appropriate, but MCS is by no
      means restricted to this particular case. With input variations simulated by
      random numbers, the functional relationship then provides the corresponding
      variations in the output in a manner which also provides its probability
      distribution. The MCS procedure thus provides output uncertainty estimates
      without the need for the differential equations associated with GUM modelling.
      The aim of this article is to demonstrate the ease with which Microsoft Excel (or
      a similar spreadsheet) can be used to provide an uncertainty estimate for
      measurands derived through a functional relationship. In addition, we also
      consider the relatively common situation where an empirically derived formula
      includes one or more 'constants', each of which has an empirically derived
      numerical value. Such empirically derived 'constants' must also have associated
      uncertainties which propagate through the functional relationship and contribute
      to the combined standard uncertainty of the measurand. 

PMID- 24659834
TI  - Genetic insights into cardiometabolic risk factors.
AB  - Many biochemical traits are recognised as risk factors, which contribute to or
      predict the development of disease. Only a few are in widespread use, usually to
      assist with treatment decisions and motivate behavioural change. The greatest
      effort has gone into evaluation of risk factors for cardiovascular disease and/or
      diabetes, with substantial overlap as 'cardiometabolic' risk. Over the past few
      years many genome-wide association studies (GWAS) have sought to account for
      variation in risk factors, with the expectation that identifying relevant
      polymorphisms would improve our understanding or prediction of disease; others
      have taken the direct approach of genomic case-control studies for the
      corresponding diseases. Large GWAS have been published for coronary heart disease
      and Type 2 diabetes, and also for associated biomarkers or risk factors including
      body mass index, lipids, C-reactive protein, urate, liver function tests, glucose
      and insulin. Results are not encouraging for personal risk prediction based on
      genotyping, mainly because known risk loci only account for a small proportion of
      risk. Overlap of allelic associations between disease and marker, as found for
      low density lipoprotein cholesterol and heart disease, supports a causal
      association, but in other cases genetic studies have cast doubt on accepted risk
      factors. Some loci show unexpected effects on multiple markers or diseases. An
      intriguing feature of risk factors is the blurring of categories shown by the
      correlation between them and the genetic overlap between diseases previously
      thought of as distinct. GWAS can provide insight into relationships between risk
      factors, biomarkers and diseases, with potential for new approaches to disease
      classification. 

PMID- 24659836
TI  - Large sample randomization inference of causal effects in the presence of
      interference.
AB  - Recently, increasing attention has focused on making causal inference when
      interference is possible. In the presence of interference, treatment may have
      several types of effects. In this paper, we consider inference about such effects
      when the population consists of groups of individuals where interference is
      possible within groups but not between groups. A two stage randomization design
      is assumed where in the first stage groups are randomized to different treatment
      allocation strategies and in the second stage individuals are randomized to
      treatment or control conditional on the strategy assigned to their group in the
      first stage. For this design, the asymptotic distributions of estimators of the
      causal effects are derived when either the number of individuals per group or the
      number of groups grows large. Under certain homogeneity assumptions, the
      asymptotic distributions provide justification for Wald-type confidence intervals
      (CIs) and tests. Empirical results demonstrate the Wald CIs have good coverage in
      finite samples and are narrower than CIs based on either the Chebyshev or
      Hoeffding inequalities provided the number of groups is not too small. The
      methods are illustrated by two examples which consider the effects of cholera
      vaccination and an intervention to encourage voting.

PMID- 24659837
TI  - Efficient Estimation of Semiparametric Transformation Models for Two-Phase Cohort
      Studies.
AB  - Under two-phase cohort designs, such as case-cohort and nested case-control
      sampling, information on observed event times, event indicators, and inexpensive
      covariates is collected in the first phase, and the first-phase information is
      used to select subjects for measurements of expensive covariates in the second
      phase; inexpensive covariates are also used in the data analysis to control for
      confounding and to evaluate interactions. This paper provides efficient
      estimation of semiparametric transformation models for such designs,
      accommodating both discrete and continuous covariates and allowing inexpensive
      and expensive covariates to be correlated. The estimation is based on the
      maximization of a modified nonparametric likelihood function through a
      generalization of the expectation-maximization algorithm. The resulting
      estimators are shown to be consistent, asymptotically normal and asymptotically
      efficient with easily estimated variances. Simulation studies demonstrate that
      the asymptotic approximations are accurate in practical situations. Empirical
      data from Wilms' tumor studies and the Atherosclerosis Risk in Communities (ARIC)
      study are presented.

PMID- 24659838
TI  - Landmark Estimation of Survival and Treatment Effect in a Randomized Clinical
      Trial.
AB  - In many studies with a survival outcome, it is often not feasible to fully
      observe the primary event of interest. This often leads to heavy censoring and
      thus, difficulty in efficiently estimating survival or comparing survival rates
      between two groups. In certain diseases, baseline covariates and the event time
      of non-fatal intermediate events may be associated with overall survival. In
      these settings, incorporating such additional information may lead to gains in
      efficiency in estimation of survival and testing for a difference in survival
      between two treatment groups. If gains in efficiency can be achieved, it may then
      be possible to decrease the sample size of patients required for a study to
      achieve a particular power level or decrease the duration of the study. Most
      existing methods for incorporating intermediate events and covariates to predict
      survival focus on estimation of relative risk parameters and/or the joint
      distribution of events under semiparametric models. However, in practice, these
      model assumptions may not hold and hence may lead to biased estimates of the
      marginal survival. In this paper, we propose a semi-nonparametric two-stage
      procedure to estimate and compare t-year survival rates by incorporating
      intermediate event information observed before some landmark time, which serves
      as a useful approach to overcome semi-competing risks issues. In a randomized
      clinical trial setting, we further improve efficiency through an additional
      calibration step. Simulation studies demonstrate substantial potential gains in
      efficiency in terms of estimation and power. We illustrate our proposed
      procedures using an AIDS Clinical Trial Protocol 175 dataset by estimating
      survival and examining the difference in survival between two treatment groups:
      zidovudine and zidovudine plus zalcitabine.

PMID- 24659839
TI  - Applying Quantitative Genetic Methods to Primate Social Behavior.
AB  - Increasingly, behavioral ecologists have applied quantitative genetic methods to
      investigate the evolution of behaviors in wild animal populations. The promise of
      quantitative genetics in unmanaged populations opens the door for simultaneous
      analysis of inheritance, phenotypic plasticity, and patterns of selection on
      behavioral phenotypes all within the same study. In this article, we describe how
      quantitative genetic techniques provide studies of the evolution of behavior with
      information that is unique and valuable. We outline technical obstacles for
      applying quantitative genetic techniques that are of particular relevance to
      studies of behavior in primates, especially those living in noncaptive
      populations, e.g., the need for pedigree information, non-Gaussian phenotypes,
      and demonstrate how many of these barriers are now surmountable. We illustrate
      this by applying recent quantitative genetic methods to spatial proximity data, a
      simple and widely collected primate social behavior, from adult rhesus macaques
      on Cayo Santiago. Our analysis shows that proximity measures are consistent
      across repeated measurements on individuals (repeatable) and that kin have
      similar mean measurements (heritable). Quantitative genetics may hold lessons of
      considerable importance for studies of primate behavior, even those without a
      specific genetic focus.

PMID- 24659841
TI  - Exploration and Adoption of Evidence-based Practice by US Child Welfare Agencies.
AB  - OBJECTIVE: To examine the extent to which child welfare agencies adopt new
      practices and to determine the barriers to and facilitators of adoption of new
      practices. METHODS: Data came from telephone interviews with the directors of the
      92 public child welfare agencies that constituted the probability sample for the
      first National Survey of Child and Adolescent Well-being (NSCAWI). In a semi
      structured 40 minute interview administered by a trained Research Associate,
      agency directors were asked about agency demographics, knowledge of evidence
      based practices, use of technical assistance and actual use of evidence-based
      practices.. Of the 92 agencies, 83 or 90% agreed to be interviewed. RESULTS:
      Agencies reported that the majority of staff had a BA degree (53.45%) and that
      they either paid for (52.6%) or provided (80.7%) continuing education. Although
      agencies routinely collect standardized child outcomes (90%) they much less
      frequently collect measures of child functioning (30.9%). Almost all agencies
      (94%) had started a new program or practice but only 24.8% were evidence-based
      and strategies used to explore new programs or practices usually involved local
      or state contracts. Factors that were associated with program success included
      internal support for the innovation (27.3%), and an existing evidence base
      (23.5%). CONCLUSIONS: Directors of child welfare agencies frequently institute
      new programs or practices but they are not often evidence-based. Because
      virtually all agencies provide some continuing education adding discussions of
      evidence-based programs/practices may spur adaption. Reliance on local and state
      colleagues to explore new programs and practices suggests that developing well
      informed social networks may be a way to increase the spread of evidence0based
      practices.

PMID- 24659840
TI  - Personality Traits in Rhesus Macaques (Macaca mulatta) Are Heritable but Do Not
      Predict Reproductive Output.
AB  - There is growing evidence that behavioral tendencies, or "personalities," in
      animals are an important aspect of their biology, yet their evolutionary basis is
      poorly understood. Specifically, how individual variation in personality arises
      and is subsequently maintained by selection remains unclear. To address this gap,
      studies of personality require explicit incorporation of genetic information.
      Here, we explored the genetic basis of personality in rhesus macaques by
      determining the heritability of personality components and by examining the
      fitness consequences of those components. We collected observational data for 108
      adult females living in three social groups in a free-ranging population via
      focal animal sampling. We applied principal component analysis to nine
      spontaneously occurring behaviors and identified six putative personality
      components, which we named Meek, Bold, Aggressive, Passive, Loner, and Nervous.
      All components were repeatable and heritable, with heritability estimates ranging
      from 0.14 to 0.35. We found no evidence of an association with reproductive
      output, measured either by infant survival or by interbirth interval, for any of
      the personality components. This finding suggests either that personality does
      not have fitness-related consequences in this population or that selection has
      acted to reduce fitness-associated variation in personality.

PMID- 24659842
TI  - Explaining variations in state foster care maintenance rates and the implications
      for implementing new evidence-based programs.
AB  - BACKGROUND: U.S. Child Welfare systems are involved in the lives of millions of
      children, and total spending exceeds $26 billion annually. Out-of-home foster
      care is a critical and expensive Child Welfare service, a major component of
      which is the maintenance rate paid to support housing and caring for a foster
      child. Maintenance rates vary widely across states and over time, but reasons for
      this variation are not well understood. As evidence-based programs are
      disseminated to state Child Welfare systems, it is important to understand what
      may be the important drivers in the uptake of these practices including state
      spending on core system areas. DATA AND METHODS: We assembled a unique,
      longitudinal, state-level panel dataset (1990-2008) for all 50 states with annual
      data on foster care maintenance rates and measures of child population in need,
      poverty, employment, urbanicity, proportion minority, political party control of
      the state legislature and governorship, federal funding, and lawsuits involving
      state foster care systems. All monetary values were expressed in per-capita terms
      and inflation adjusted to 2008 dollars. We used longitudinal panel regressions
      with robust standard errors and state and year fixed effects to estimate the
      relationship between state foster care maintenance rates and the other factors in
      our dataset, lagging all factors by one year to mitigate the possibility that
      maintenance rates influenced their predictors. Exploratory analyses related
      maintenance rates to Child Welfare outcomes. FINDINGS: State foster care
      maintenance rates have increased in nominal terms, but in many states, have not
      kept pace with inflation, leading to lower real rates in 2008 compared to those
      in 1991 for 54% of states for 2 year-olds, 58% for 9 year-olds, and 65% for 16
      year-olds. In multivariate analyses including socioeconomic, demographic, and
      political factors, monthly foster care maintenance rates declined $15 for each 1%
      increase in state unemployment and declined $40 if a state's governorship and
      legislature became Republican, though significance was marginal. In analyses also
      examining state revenue, federal funding, and legal challenges, maintenance rates
      increased as the federal share of maximum TANF payments increased. However, >50%
      of variation in foster care maintenance rates was explained by unobserved state
      level factors as measured by state fixed effects. These factors did not appear to
      be strongly related to 2008 Child Welfare outcomes like foster care placement
      stability and maltreatment which were also not correlated with foster care
      maintenance rates. CONCLUSIONS: Despite being part of a social safety net, foster
      care maintenance rates have declined in real terms since 1991 in many states, and
      there is no strong evidence that they increase in response to harsher economic
      climates or to federal programs or legal reviews. State variation in maintenance
      rates was not related to Child Welfare outcomes, though further analysis of this
      important relationship is needed. Variability in state foster care maintenance
      rates appears highly idiosyncratic, an important contextual factor to consider
      when designing and disseminating evidence-based services.

PMID- 24659843
TI  - Sibling Conversations about Dating and Sexuality: Sisters as Confidants, Sources
      of Support, and Mentors.
AB  - Using an observational methodology to examine sibling communication, sisters (N =
      28 dyads) were videotaped discussing their ideas about dating and sexuality.
      Social provision theory was used as a framework for the examination of roles
      enacted by sisters during these conversations. Inductive thematic analytic
      procedures were conducted and three roles were identified: sisters as confidants,
      sources of support, and mentors. Older and younger sisters both served as
      confidants and sources of support for one another, whereas, older sisters were
      more likely to be mentors for their younger sisters than vice versa. Findings
      indicate the potential importance of sisters in the formation of adolescent
      girls' ideas about romantic relationships and sexuality, sibling communication as
      a socialization mechanism of sisters' similarities in romantic experiences and
      sexual behaviors/attitudes, and the inclusion of older sisters in prevention
      intervention programs focused on reducing adolescent sexual risk behaviors and
      promoting healthy romantic relationships and sexuality development.

PMID- 24659844
TI  - Enhancing engagement between the population, environment, and climate research
      communities: the shared socio-economic pathway process.
AB  - Demographers have much to contribute to climate change science. This paper
      describes a new framework being developed by the climate research community that
      holds potential as an organizing tool for population-climate scholarship, as well
      as being useful for identifying demographic research gaps within the climate
      change field. The shared socio-economic pathways (SSPs) represent plausible
      alternative trends in the evolution of social and natural systems over the twenty
      first century at the scale of the world and large regions. The SSPs can help
      identify population-environment research gaps by illuminating areas of
      intersection that will shape climate futures but require deeper scientific
      understanding-the association between urbanization and energy consumption is an
      example. Also, to vastly enhance the policy relevance of local case studies, the
      parameters outlined within the SSPs can offer a basic level of harmonization to
      facilitate generalization. In this way, the SSP framework can increase the
      relevance and accessibility of population research and, therefore, offer a
      mechanism through which demographic science can truly offer policy impact.

PMID- 24659845
TI  - Internal consistency of demographic assumptions in the shared socioeconomic
      pathways.
AB  - A new set of alternative socioeconomic scenarios for climate change researches
      the shared socioeconomic pathways (SSPs)-includes for the first time a more
      comprehensive set of demographic conditions on population, urbanization, and
      education as the central scenario elements, along with other aspects of society,
      in order to facilitate better analyses of challenges to climate change mitigation
      and adaptation. However, it also raises a new question about the internal
      consistency of assumptions on different demographic and economic trends under
      each SSP. This paper examines whether the interactions between the demographic
      and economic factors implied by the assumptions in the SSP projections are
      consistent with the research literature, and whether they are consistently
      represented in the projection results. Our analysis shows that the interactions
      implied by the demographic assumptions in the SSPs are generally consistent with
      findings from the literature, and the majority of the assumed relationships are
      also evident in the projected trends. It also reveals some inconsistency issues,
      resulting mainly from the use of inconsistent definitions of regions and
      limitations in our understanding of future changes in the patterns of
      interactions at different stages of socioeconomic development. Finally, we offer
      recommendations on how to improve demographic assumptions in the extended SSPs,
      and how to use the projections of SSP central elements in climate change
      research.

PMID- 24659846
TI  - CENTER PROBLEM FOR A THIRD-ORDER ODES.
AB  - We obtain necessary and sufficient conditions for the existence of a center on a
      local center manifold for three 4-parameter families of quadratic systems on R3.
      We also give a positive answer to an open question posed in [Dias & Mello(2010)]
      related to similar systems.

PMID- 24659847
TI  - Serum omentin-1 as a disease activity marker for Crohn's disease.
AB  - BACKGROUND AND AIM: It remains challenging to determine the inflammatory activity
      in Crohn's disease (CD) for lack of specific laboratory markers. Recent studies
      suggest that serum omentin-1 is associated with inflammatory response. We aimed
      to assess the potential of serum omentin-1 as a marker of disease activity in CD
      patients. METHODS: Serum omentin-1 concentrations were determined by enzyme
      linked immunosorbent assay (ELISA) in patients with CD (n = 240), functional
      gastrointestinal disorders (FGDs, n = 120), and healthy controls (HC, n = 60) and
      evaluated for correlation with disease activity. Expression of omentin-1 in
      colonic tissues from patients with CD was also analyzed by real-time PCR and
      Western blotting. Serum omentin-1 levels as an activity index were evaluated
      using a receiver operating characteristic (ROC) curve. RESULTS: Serum omentin-1
      concentrations were significantly decreased in active CD patients compared with
      patients in remission, FGDs, and HC (all P < 0.001). Expression of omentin-1 was
      decreased at mRNA and protein levels in inflamed colonic tissues in active CD
      than that in noninflamed colonic tissues. Serum omentin-1 levels were negatively
      correlated with disease activity in CD, better than C-reactive protein (CRP).
      CONCLUSION: Our results indicate that serum and colonic omentin-1 expressions are
      decreased in active CD patients. The correlation of serum omentin-1 with disease
      activity in CD is superior to that of CRP. Serum omentin-1 is a potential marker
      for CD disease activity.

PMID- 24659848
TI  - Interleukin-6 and C-reactive protein are overexpressed in the liver of perinatal
      deaths diagnosed with fetal inflammatory response syndrome.
AB  - Anatomopathologic studies have failed to define the fetal inflammatory response
      syndrome (FIRS) as a cause of fetal death. Here, liver fragments of perinatal
      autopsies were collected at a university hospital from 1990 to 2009 and
      classified according to the cause of death, perinatal stress, and gestational age
      (GA) of the fetus. IL-6, TNF-alpha, and C-reactive protein (CRP) expression were
      immunostained, respectively, with primary antibody. Cases with congenital
      malformation, ascending infection, and perinatal anoxia showed increased IL-6,
      CRP, and TNF-alpha, respectively. Prematures presented higher expression of IL-6
      whereas term births showed higher expression of CRP. Cases classified as acute
      stress presented higher expression of IL-6 and TNF-alpha and cases with chronic
      stress presented higher expression of CRP. GA correlated negatively with IL-6 and
      positively with CRP and TNF-alpha. Body weight correlated negatively with IL-6
      and positively with CRP and TNF-alpha. Despite the diagnosis of FIRS being
      clinical and based on serum parameters, the findings in the current study allow
      the inference of FIRS diagnosis in the autopsied infants, based on an in situ
      liver analysis of these markers.

PMID- 24659850
TI  - Simplified and economical 2D IR spectrometer design using a dual acousto-optic
      modulator.
AB  - Over the last decade two-dimensional infrared (2D IR) spectroscopy has proven to
      be a very useful extension of infrared spectroscopy, yet the technique remains
      restricted to a small group of specialized researchers because of its
      experimental complexity and high equipment cost. We report on a spectrometer that
      is compact, mechanically robust, and is much less expensive than previous designs
      because it uses a single pixel MCT detector rather than an array detector.
      Moreover, each axis of the spectrum can be collected in either the time or
      frequency domain via computer programming. We discuss pulse sequences for
      scanning the probe axis, which were not previously possible. We present spectra
      on metal carbonyl compounds at 5 um and a model peptide at 6 um. Data collection
      with a single pixel MCT takes longer than using an array detector, but
      publishable quality data are still achieved with only a few minutes of averaging.

PMID- 24659849
TI  - Identification of differentially expressed serum proteins in infectious purpura
      fulminans.
AB  - Purpura fulminans (PF) is a life-threatening hemorrhagic condition. Because of
      the rarity and randomness of the disease, no improvement in treatment has been
      made for a long time. In this study, we assessed the serum proteome response to
      PF by comparing serum proteins between healthy controls and PF patient. Liquid
      chromatography with tandem mass spectrometry (LC-MS/MS) approach was used after
      depleting 6 abundant proteins of serum. In total, 262 proteins were confidently
      identified with 2 unique peptides, and 38 proteins were identified significantly
      up- (>= 2) or downregulated (<= 0.5) based on spectral counting ratios (SpCPF/N).
      In the 38 proteins with significant abundance changes, 11 proteins were
      previously known to be associated with burn or sepsis response, but 27
      potentially novel proteins may be specifically associated with PF process. Two
      differentially expressed proteins, alpha-1-antitrypsin (SERPINA1) and alpha-2
      antiplasmin (SERPINF2), were validated by Western blot. This is the first study
      where PF patient and healthy controls are compared in a proteomic study to
      elucidate proteins involved in the response to PF. This study provides an initial
      basis for future studies of PF, and the differentially expressed proteins might
      provide new therapeutic targets to decrease the mortality of PF.

PMID- 24659851
TI  - Mate-guarding constrains feeding activity but not energetic status of wild male
      long-tailed macaques (Macaca fascicularis).
AB  - Mate-guarding is an important determinant of male reproductive success in a
      number of species. Little is known however about the constraints of this
      behaviour, e.g. the associated energetic costs. We investigated these costs in
      long-tailed macaques where alpha males mate guard females to a lesser extent than
      predicted by the priority of access model. The study was carried out during two
      mating periods on three wild groups living in the Gunung Leuser National Park,
      Indonesia. We combined behavioural observations on males' locomotion and feeding
      activity, GPS records of distance travelled and non-invasive measurements of
      urinary C-peptide (UCP), a physiological indicator of male energetic status. Mate
      guarding led to a decrease in feeding time and fruit consumption suggesting a
      reduced intake of energy. At the same time, vertical locomotion was reduced,
      which potentially saved energy. These findings, together with the fact that we
      did not find an effect of mate-guarding on UCP levels, suggest that energy intake
      and expenditure was balanced during mate-guarding in our study males. Mate
      guarding thus seems to not be energetically costly under all circumstances. Given
      that in strictly seasonal rhesus macaques, high-ranking males lose physical
      condition over the mating period, we hypothesise that the energetic costs of mate
      guarding vary inter-specifically depending on the degree of seasonality and that
      males of non-strictly seasonal species might be better adapted to maintain
      balanced energetic condition year-round. Finally, our results illustrate the
      importance of combining behavioural assessments of both energy intake and
      expenditure with physiological measures when investigating energetic costs of
      behavioural strategies.

PMID- 24659852
TI  - Importation, SES-selective Acculturation, and the Weaker SES-health Gradients of
      Mexican Immigrants in the United States.
AB  - Previous studies find U.S. immigrants have weaker socioeconomic gradients in
      health relative to non-Hispanic whites and their U.S.-born co-ethnics. Several
      explanations have been advanced but few have been tested empirically. We use data
      from the Mexican Family Life Survey and the U.S. National Health Interview
      Survey, including longitudinal data in the former measuring SES and health
      previous to emigration, to test if 1) immigrants "import" their gradients from
      the sending country, or if 2) they may be changing as a result of SES-graded
      acculturation among Mexican migrant men in two health indicators: obesity and
      current smoking. We find evidence consistent with the first hypothesis: the
      gradients of migrants measured prior to coming to the U.S. are not statistically
      different from those of non-migrants, as the gradients of each are relatively
      weak. Although the gradients for obesity and smoking appear to weaken with time
      spent in the U.S., the differences are not significant, suggesting little support
      for the selective acculturation hypothesis.

PMID- 24659853
TI  - Rewards of reading: Toward the development of possible selves and identities.
AB  - Children's voluntary reading positively correlates with school grades, vocabulary
      growth, reading comprehension, verbal fluency, general information, and attitudes
      towards reading. Drawing on qualitative interviews collected alongside six waves
      of longitudinal survey data in an urban setting in eastern USA, We argue that
      voluntary reading by adolescents also provides learning opportunities that
      scaffold identity formation, afford 'spaces' where youth rehearse and
      relationally enact gender roles, ethnic/racial identification, and fashion
      educational aspirations. The interviews with African American and European
      American youth were conducted in five visits and spanned 3 years through senior
      high school and 1 year post-high school. Methods of inductive and narrative
      analysis identified patterns of benefits and potential drawbacks of voluntary
      reading. Amount of voluntary reading was affected by school, family, and social
      and work commitment pressures, and fulfilled a number of broad roles. What and
      how youth were reading was as important as the amount. Significantly, reading
      allowed adolescents to explore possible selves-an interest in historical figures
      helped one African American male to develop values resisting stereotypes of male
      or African American, just as an African American female came to resist conforming
      to gender and racial stereotypes in dress and occupational ambitions.
      Relationships between voluntary reading habits, family context and educational
      aspirations were identifiable for a number of the interviewees.

PMID- 24659855
TI  - Comparison of Student Self-Reported and Administrative Data Regarding
      Intercession into Alcohol Misuse among College Freshmen Dormitory Residents.
AB  - Intercession into collegiate alcohol misuse by the Department of Resident Live
      (DRL) in freshmen dormitories at one large, Mid-Atlantic, diverse, public
      university was examined. Freshmen dormitory resident drinkers (n=357), 71% of
      whom reported alcohol misuse, were surveyed. Student self-report and DRL
      documentation, respectively, revealed that 6.4% and 7.8% (Kappa=.77) of drinkers
      were documented with an alcohol violation, 4.2% and 3.4% (Kappa=.81) lost housing
      priority points, 1.4% and .6% (Kappa=.28) were referred for alcohol counseling,
      and 1.4% and .3% (Kappa = .33) were taken to the emergency room. DRL infrequently
      interceded into alcohol misuse, perhaps because most misuse occurred off-campus.

PMID- 24659854
TI  - Combined liver and multivisceral resections.
AB  - Background. Combined liver and multivisceral resections are infrequent
      procedures, which demand extensive experience and considerable surgical skills.
      Methods. An electronic search of literature related to this topic published
      before June 2013 was performed. Results. There is limited scientific evidence of
      the feasibility and clinical outcomes of these complex procedures. The majority
      of these cases are simultaneous resections of colorectal tumors with liver
      metastases. Combined liver and multivisceral resections can be performed with
      acceptable postoperative morbidity and mortality rates only in carefully selected
      patients. Conclusion. Lack of experience in these aggressive surgeries justifies
      a careful selection of patients, considering their comorbidities. 

PMID- 24659856
TI  - The Determinants of Federal and State Enforcement of Workplace Safety
      Regulations: OSHA Inspections 1990-2010.
AB  - We explore the determinants of inspection outcomes across 1.6 million
      Occupational Safety and Health Agency (OSHA) audits from 1990 through 2010. We
      find that discretion in enforcement differs in state and federally conducted
      inspections. State agencies are more sensitive to local economic conditions,
      finding fewer standard violations and fewer serious violations as unemployment
      increases. Larger companies receive greater lenience in multiple dimensions.
      Inspector issued fines and final fines, after negotiated reductions, are both
      smaller during Republican presidencies. Quantile regression analysis reveals that
      Presidential and Congressional party affiliations have their greatest impact on
      the largest negotiated reductions in fines.

PMID- 24659857
TI  - A Novel Real-time Carbon Dioxide Analyzer for Health and Environmental
      Applications.
AB  - To be able to detect carbon dioxide (CO2) with high accuracy and fast response
      time is critical for many health and environmental applications. We report on a
      pocket-sized CO2 sensor for real-time analysis of end-tidal CO2, and
      environmental CO2. The sensor shows fast and reversible response to CO2 over a
      wide concentration range, covering the needs of both environmental and health
      applications. It is also immune to the presence of various interfering gases in
      ambient or expired air. Furthermore, the sensor has been used for real-time
      breath analysis, and the results are in good agreement with those from a
      commercial CO2 detector.

PMID- 24659858
TI  - Surgical strategy, methods of reconstruction, surgical margins and postoperative
      complications in oncoplastic breast surgery.
AB  - BACKGROUND: Oncoplastic breast surgery is an evolving discipline in the surgical
      treatment of breast cancer aimed to improve the outcome. METHODS: Oncoplastic
      breast surgery was performed between January 2008 and December 2010 on 72 women
      with 74 breast cancers selected from a population of 1,018 primary breast cancer
      patients. Careful preoperative planning revealed the possibility of partial
      breast reconstruction with volume reduction, volume displacement or volume
      replacement depending on breast size as well as tumour size and location. Data
      were registered consecutively. RESULTS: The surgical plan was successful in all
      but one case, where a mastectomy had to be performed during the primary surgery.
      In 53 cases, a contralateral mammoplasty was performed during the operation to
      achieve symmetry. During the follow-up period until November 2011, only one
      patient needed corrective surgery. Final histopathological examination indicated
      that seven cases required extended resection and three cases required a
      mastectomy. Five patients experienced delayed wound healing, although
      complications requiring further surgery occurred for the reconstructed breast in
      four cases, the contralateral breast in three cases and the axilla after
      exaeresis in two cases because of haematoma. Such complications led to slight
      delay in adjuvant therapy for four patients. CONCLUSIONS: This study demonstrates
      that it is feasible to implement oncoplastic breast surgery into daily clinical
      practice as a supplement to conventional breast cancer surgery. As such,
      oncoplastic breast surgery may provide a markedly better outcome than breast
      conserving surgery in terms of shape and symmetry without compromising the
      surgical margins. Level of Evidence: Level IV, prognostic/risk study.

PMID- 24659859
TI  - Intravitreal inflammation: from benchside to bedside 2013.

PMID- 24659860
TI  - Five-month observation of persistent diabetic macular edema after intravitreal
      injection of Ozurdex implant.
AB  - AIMS: This retrospective analysis was aimed at evaluating the effectiveness of
      treatment of persistent diabetic macular edema with intravitreal injections of
      0.7 mg dexamethasone implant Ozurdex. The study comprised three male patients (6
      eyes). RESULTS: The average thickness of the retina at baseline was 632  MUm, the
      medial BCVA was 0.8 logMAR, and corrected intraocular pressure was 13.7 mmHg. The
      maximum decrease in mean retinal thickness was observed at four weeks following
      the treatment and was 365  MUm (-267  MUm) and visual acuity improved by an
      average of two lines and was 0.6 logMAR. The largest increase in mean retinal
      thickness to average of 528  MUm (+164  MUm) occurred at 16 weeks and the average
      BCVA was 0.614 lines BCVA logMAR. In one eye, there was a steroid cataract
      development after the third dose of dexamethasone implant of 0.7 mg. CONCLUSIONS:
      The intravitreal dexamethasone implant treatment of patients with persistent
      diabetic macular edema in whom laser photocoagulation proved to be ineffective
      and as a result they required a monthly injection of anti-VEGF factors
      (Ranibizumab, Bevacizumab) may be a good alternative to extending the interval of
      injections. However, reinjections involve a high risk of developing poststeroid
      cataracts, which is not without significance in middle-aged patients.

PMID- 24659861
TI  - Placental origin of prostaglandin F2alpha in the domestic cat.
AB  - In the present study, the question was addressed whether the feline placenta can
      synthesize prostaglandin F2alpha (PGF2alpha). The PGFS protein was elevated,
      particularly at 2.5-3 weeks of pregnancy compared to 7-8 (P < 0.05) and 8.5-9
      weeks (P < 0.001). Transcripts for PGFS were significantly upregulated at 2.5-3
      weeks of pregnancy and then gradually declined towards the end of gestation (P <
      0.001). Transcripts for PTGS2 were only upregulated in placentas from queens
      close to term (P < 0.001) compared with earlier phases. Staining of PTGS2 showed
      distinct positive signals in placentas obtained during the last week before
      labor, particularly in the strongly invading trophoblast surrounding blood
      vessels, and also in decidual cells. Shortly after implantation, signals for PGFS
      were localized in the trophoblast cells. Near term, PGFS staining was seen mainly
      in decidual cells. Both placental PGF2alpha and plasma PGFM were elevated towards
      the end of pregnancy (P < 0.001) compared with earlier weeks of pregnancy. The
      content of PGF2alpha in extracted placenta mirrored the PGFM level in plasma of
      pregnant females. During late gestation there is a significant increase in PGFM
      levels in maternal blood and of PGF2alpha levels in placental tissue concomitant
      with an upregulation of placental PTGS2.

PMID- 24659862
TI  - IL-27 activates human trophoblasts to express IP-10 and IL-6: implications in the
      immunopathophysiology of preeclampsia.
AB  - PURPOSE: To investigate the effects of IL-27 on human trophoblasts and the
      underlying regulatory signaling mechanisms in preeclampsia. METHODS: The
      expression of IL-27 and IL-27 receptor (WSX-1) was studied in the placenta or
      sera from patients with preeclampsia. In vitro, we investigated the effects of IL
      27 alone or in combination with inflammatory cytokine tumor necrosis factor (TNF
      alpha) on the proinflammatory activation of human trophoblast cells (HTR-8/SVneo)
      and the underlying intracellular signaling molecules. RESULTS: The expression of
      IL-27 and IL-27 receptor alpha (WSX-1) was significantly elevated in the
      trophoblastic cells from the placenta of patients with preeclampsia compared with
      control specimens. In vitro, IL-27 could induce the expression of inflammatory
      factors IFN-gamma-inducible protein 10 (CXCL10/IP-10) and IL-6 in trophoblasts,
      and a synergistic effect was observed in the combined treatment of IL-27 and TNF
      alpha on the release of IP-10 and IL-6. Furthermore, the production of IP-10 and
      IL-6 stimulated by IL-27 was differentially regulated by intracellular activation
      of phosphatidylinositol 3-OH kinase-AKT, p38MAPK, and JAK/STAT pathways.
      CONCLUSIONS: These results provide a new insight into the IL-27-activated
      immunopathological effects mediated by distinct intracellular signal transduction
      molecules in preeclampsia.

PMID- 24659863
TI  - Retrieval Expectations Affect False Recollection: Insights from a Criterial
      Recollection Task.
AB  - People use retrieval expectations to guide the accuracy of recollection attempts.
      This retrieval monitoring process minimizes illusory or false recollection,
      especially when the to-be-remembered events are distinctive. Our work with a
      criterial recollection task reveals that this monitoring process primarily
      depends on qualitative features of recollected information, an aspect of memory
      that can be dissociated from traditional measures of recollection frequency and
      familiarity. Neuroimaging and brain damage studies further indicate that this
      monitoring process relies on prefrontal regions that coordinate memory retrieval.
      This research helps explain why older adults are sometimes more susceptible to
      false recollection. More generally, this research highlights the importance of
      different kinds of recollected events and corresponding retrieval expectations in
      determining memory accuracy.

PMID- 24659864
TI  - Adjuncts to colonic cleansing before colonoscopy.
AB  - Pre-procedural cleansing of the bowel can maximize the effectiveness and
      efficiency of colonoscopy. Yet, efficacy of the current gold standard colonic
      preparation method - high-volume oral administration of purgative agents 12-24 h
      prior to the procedure - is limited by several factors, such as patient
      compliance (due to poor palatability and inconvenience of the dosing regimen) and
      risks of complications (due to drug interactions or intolerance). Attempts to
      resolve these limitations have included providing adjunctive agents and methods
      to promote the colonic cleansing ability of the principal purgative agent, with
      the aim of lessening unpleasant side effects (such as bloating) and reducing the
      large ingested volume requirement. Several promising adjunctive agents are
      bisacodyl, magnesium citrate, senna, simethicone, metoclopramide, and
      prokinetics, and each are being investigated for their potential. This review
      provides an up to date summary of the reported investigations into the potencies
      and weaknesses of the key adjuncts currently being applied in clinic as
      supplements to the traditional bowel preparation agents. While the comparative
      analysis of these adjuncts showed that no single agent or method has yet achieved
      the goal of completely overcoming the limitations of the current gold standard
      preparation method, they at least provide endoscopists with an array of
      alternatives to help improve the suboptimal efficacy of the main cleansing
      solutions when used alone. To aid in this clinical endeavor, a subjective grade
      was assigned to each adjunct to indicate its practical value. In addition, the
      systematic review of the currently available agents and methods provides insight
      into the features of each that may be overcome or exploited to create novel drugs
      and strategies that may become adopted as effective bowel cleansing adjuncts or
      alternatives. 

PMID- 24659865
TI  - What is the best strategy for successful bowel preparation under special
      conditions?
AB  - Adequate bowel preparation is important for successful colonoscopic examination.
      Several effective colonic cleansing agents are available and routinely
      prescribed, but each carries its own limitations and benefits from particular
      dosing regimens. The most frequently prescribed colonic cleansing agent, the
      polyethylene glycol (PEG) cathartic solution, suffers from low patient compliance
      in general, due to its unpalatable taste and smell coupled with the large
      ingested volumes required. However, PEG is preferred over other cathartics for
      use in individuals of advanced age, sufferers of chronic kidney disease, heart
      failure and inflammatory bowel disease, and women who are pregnant or lactating.
      The laxative agents sodium phosphate (NaP) and sodium picosulfate plus magnesium
      citrate have been applied and have improved patient compliance and tolerance.
      NaP, however, should be avoided in individuals with impaired renal function or
      plasma clearance, such as those with chronic kidney disease, who are taking drugs
      that affect renal function, or who suffer from heart failure. Other special
      conditions that may affect an individual's tolerance of the cathartic agent or
      ability to complete the administration routine include stroke, severe
      constipation, hematochezia, suspicious lower gastrointestinal bleeding, and
      mental disorders such as dementia. All ingestible bowel preparation solutions can
      be instilled into the stomach and duodenum through nasogastric tube or
      esophagogastroduodenoscope with the aid of a water irrigation pump for patients
      with difficulties swallowing or ingesting the large volumes of fluid required. In
      addition, dietary regimens based on clear liquids and low-residue foods for 1-4 d
      prior to the colonoscopy may be supplemental bowel preparation strategies.
      Achieving an effective and safe cleansing of the bowel is important for
      successful colonoscopy in all patients, so full knowledge of the individual's
      condition and capabilities is necessary to select the most appropriate colonic
      cleansing agent and delivery regimen. 

PMID- 24659866
TI  - Bowel preparations as quality indicators for colonoscopy.
AB  - Colonoscopy is the principal investigative procedure for colorectal neoplasms
      because it can detect and remove most precancerous lesions. The effectiveness of
      colonoscopy depends on the quality of the examination. Bowel preparation is an
      essential part of high-quality colonoscopies because only an optimal colonic
      cleansing allows the colonoscopist to clearly view the entire colonic mucosa and
      to identify any polyps or other lesions. Suboptimal bowel preparation not only
      prolongs the overall procedure time, decreases the cecal intubation rate, and
      increases the costs associated with colonoscopy but also increases the risk of
      missing polyps or adenomas during the colonoscopy. Therefore, a repeat
      examination or a shorter colonoscopy follow-up interval may be suitable
      strategies for a patient with suboptimal bowel preparation. 

PMID- 24659867
TI  - Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue
      lymphoma.
AB  - Gastrointestinal lymphoma is the most common type of extranodal lymphoma, and
      most commonly affects the stomach. Marginal zone B-cell lymphoma of the mucosa
      associated lymphoid tissue (MALT) and diffuse large B-cell lymphoma are the most
      common histologic types of gastric lymphoma. Despite its increasing incidence,
      diagnosis of gastric lymphoma is difficult at an earlier stage due to its
      nonspecific symptoms and endoscopic findings, and, thus, a high index of
      suspicion, and multiple, deep, repeated biopsies at abnormally and normally
      appearing sites in the stomach are needed. In addition, testing for Helicobacter
      pylori (H. pylori) infection and endoscopic ultrasonography to determine the
      depth of tumor invasion and involvement of regional lymph nodes is essential for
      predicting response to H. pylori eradication and for assessment of disease
      progression. In addition, H. pylori infection and MALT lymphoma development are
      associated, and complete regression of low-grade MALT lymphomas after H. pylori
      eradication has been demonstrated. Radiotherapy and/or chemotherapy can be used
      in cases that show poor response to H. pylori eradication, negativity for H.
      pylori infection, or high-grade lymphoma. 

PMID- 24659868
TI  - Efficacy of Helicobacter pylori eradication for the prevention of metachronous
      gastric cancer after endoscopic resection for early gastric cancer.
AB  - Helicobacter pylori (H. pylori) plays an important role in gastric
      carcinogenesis, as the majority of gastric cancers develop from H. pylori
      infected gastric mucosa. The rate of early gastric cancer diagnosis has increased
      in Japan and Korea, where H. pylori infection and gastric cancer are highly
      prevalent. Early intestinal-type gastric cancer without concomitant lymph node
      metastasis is usually treated by endoscopic resection. Secondary metachronous
      gastric cancers often develop because atrophic mucosa left untreated after
      endoscopic treatment confers a high risk of gastric cancer. The efficacy of H.
      pylori eradication for the prevention of metachronous gastric cancer remains
      controversial. However, in patients who undergo endoscopic resection of early
      gastric cancer, H. pylori eradication is recommended to suppress or delay
      metachronous gastric cancer. Careful and regularly scheduled endoscopy should be
      performed to detect minute metachronous gastric cancer after endoscopic
      resection. 

PMID- 24659869
TI  - Helicobacter pylori infection following partial gastrectomy for gastric cancer.
AB  - Gastric remnants are an inevitable consequence of partial gastrectomy following
      resection for gastric cancer. The presence of gastric stumps is itself a risk
      factor for redevelopment of gastric cancer. Helicobacter pylori (H. pylori)
      infection is also a well-known characteristic of gastric carcinogenesis. H.
      pylori colonization in the remnant stomach therefore draws special interest from
      clinicians in terms of stomach cancer development and pathogenesis; however, the
      H. pylori-infected gastric remnant is quite different from the intact organ in
      several aspects and researchers have expressed conflicting opinions with respect
      to its role in pathogenesis. For instance, H. pylori infection of the gastric
      stump produced controversial results in several recent studies. The prevalence of
      H. pylori infection in the gastric stump has varied among recent reports.
      Gastritis developing in the remnant stomach presents with a unique pattern of
      inflammation that is different from the pattern seen in ordinary gastritis of the
      intact organ. Bile refluxate also has a significant influence on the colonization
      of the stomach stump, with several studies reporting mixed results as well. In
      contrast, the elimination of H. pylori from the gastric stump has shown a
      dramatic impact on eradication rate. H. pylori elimination is recognized to be
      important for cancer prevention and considerable agreement of opinion is seen
      among researchers. To overcome the current discrepancies in the literature
      regarding the role of H. pylori in the gastric stump, further research is
      required. 

PMID- 24659870
TI  - Challenges in managing hepatitis C virus infection in cancer patients.
AB  - Cancer patients have unique problems associated with hepatitis C virus (HCV)
      infection and treatment not seen in the general population. HCV infection poses
      additional challenges and considerations for the management of cancer, and vice
      versa. HCV infection also can lead to the development of cancer, particularly
      hepatocellular carcinoma and non-Hodgkin lymphoma. In severely immunocompromised
      cancer patients, diagnosis of HCV infection requires increased reliance on RNA
      detection techniques. HCV infection can affect chemotherapy, and delay of HCV
      infection treatment until completion of chemotherapy and achievement of cancer
      remission may be required to decrease the potential for drug-drug interactions
      between antineoplastic agents and HCV therapeutics and potentiation of side
      effects of these agents. In addition, hematopoietic stem cell transplant (HSCT)
      recipients have an increased risk of early development of cirrhosis and fibrosis.
      Whether this increased risk applies to all patients regardless of cancer
      treatment is unknown. Furthermore, patients with cancer may have poorer sustained
      virological responses to HCV infection treatment than do those without cancer.
      Unfortunately, not all cancer patients are candidates for HCV infection therapy.
      In this article, we review the challenges in managing HCV infection in cancer
      patients and HSCT recipients. 

PMID- 24659871
TI  - Role of macrophages and monocytes in hepatitis C virus infections.
AB  - A number of studies conducted over many years have shown that hepatitis C virus
      (HCV) can infect a variety of cell types. In vivo infection of monocytes,
      macrophages, and dendritic cells by HCV has been frequently shown by a number of
      researchers. These studies have demonstrated replication of HCV by detecting the
      presence of both negative genomic strands and a variety of non-structural HCV
      proteins in infected cells. In addition, analyses of genome sequences have also
      shown that different cell types can harbor different HCV variants. Investigators
      have also done preliminary studies of which cellular genes are affected by HCV
      infection, but there have not yet been a sufficient number of these studies to
      understand the effects of infection on these cells. Analyses of in vitro HCV
      replication have shown that monocytes, macrophages and dendritic cells can be
      infected by HCV from patient sera or plasma. These studies suggest that entry and
      cellular locations may vary between different cell types. Some studies suggest
      that macrophages may preferentially allow HCV genotype 1 to replicate, but
      macrophages do not appear to select particular hypervariable regions. Overall,
      these studies agree with a model where monocytes and macrophages act as an
      amplification system, in which these cells are infected and show few cytopathic
      effects, but continuously produce HCV. This allows them to produce virus over an
      extended time and allows its spread to other cell types. 

PMID- 24659872
TI  - Establishment of chronic hepatitis C virus infection: translational evasion of
      oxidative defence.
AB  - Hepatitis C virus (HCV) causes a clinically important disease affecting 3% of the
      world population. HCV is a single-stranded, positive-sense RNA virus belonging to
      the genus Hepacivirus within the Flaviviridae family. The virus establishes a
      chronic infection in the face of an active host oxidative defence, thus
      adaptation to oxidative stress is key to virus survival. Being a small RNA virus
      with a limited genomic capacity, we speculate that HCV deploys a different
      strategy to evade host oxidative defence. Instead of counteracting oxidative
      stress, it utilizes oxidative stress to facilitate its own survival. Translation
      is the first step in the replication of a plus strand RNA virus so it would make
      sense if the virus can exploit the host oxidative defence in facilitating this
      very first step. This is particularly true when HCV utilizes an internal ribosome
      entry site element in translation, which is distinctive from that of cap
      dependent translation of the vast majority of cellular genes, thus allowing
      selective translation of genes under conditions when global protein synthesis is
      compromised. Indeed, we were the first to show that HCV translation was
      stimulated by an important pro-oxidant-hydrogen peroxide in hepatocytes,
      suggesting that HCV is able to adapt to and utilize the host anti-viral response
      to facilitate its own translation thus allowing the virus to thrive under
      oxidative stress condition to establish chronicity. Understanding how HCV
      translation is regulated under oxidative stress condition will advance our
      knowledge on how HCV establishes chronicity. As chronicity is the initiator step
      in disease progression this will eventually lead to a better understanding of
      pathogenicity, which is particularly relevant to the development of anti-virals
      and improved treatments of HCV patients using anti-oxidants. 

PMID- 24659873
TI  - Kidney transplantation from donors with hepatitis C infection.
AB  - The increasing demand for organ donors to supply the increasing number of
      patients on kidney waiting lists has led to most transplant centers developing
      protocols that allow safe utilization from donors with special clinical
      situations which previously were regarded as contraindications. Deceased donors
      with previous hepatitis C infection may represent a safe resource to expand the
      donor pool. When allocated to serology-matched recipients, kidney transplantation
      from donors with hepatitis C may result in an excellent short-term outcome and a
      significant reduction of time on the waiting list. Special care must be dedicated
      to the pre-transplant evaluation of potential candidates, particularly with
      regard to liver functionality and evidence of liver histological damage, such as
      cirrhosis, that could be a contraindication to transplantation. Pre-transplant
      antiviral therapy could be useful to reduce the viral load and to improve the
      long-term results, which may be affected by the progression of liver disease in
      the recipients. An accurate selection of both donor and recipient is mandatory to
      achieve a satisfactory long-term outcome. 

PMID- 24659874
TI  - Histopathological evaluation of recurrent hepatitis C after liver
      transplantation: a review.
AB  - Although the morphological features of hepatitis C virus (HCV) recurrence after
      orthotopic liver transplantation (OLT) have been well established in the last
      decades, the differential diagnosis still represents a challenge for the
      pathologist, especially early recurrent hepatitis C vs mild acute cellular
      rejection. The present review focuses on the role of the pathologist and the
      pathology laboratory in the management of recipients with recurrent hepatitis C,
      the usefulness of early and late post-OLT liver biopsies, and the potential role
      of ancillary techniques (immunohistochemistry and reverse transcription
      polymerase chain reaction, RT-PCR). The English literature on the topic is
      reviewed, focusing on the histopathology, the immunohistochemistry and the use of
      RT-PCR on HCV-positive post-OLT biopsies. The different histopathological
      illustrations of early and chronic recurrent hepatitis C are presented, with
      special focus on the main differential diagnoses and those features with
      prognostic relevance (cholestasis above all). The usefulness of ancillary
      techniques are discussed, especially HCV RNA quantitation by RT-PCR. Finally, the
      usefulness of long-term protocol biopsies is addressed: their usefulness for the
      study of allograft disease progression is clear, but their meaning in the long
      term is still debated. The significance of plasma cell infiltrate in HCV-positive
      allografts, the prognostic weight of graft steatosis, and the impact of donor age
      in recurrent hepatitis C also represent additional open issues. 

PMID- 24659875
TI  - Hepatitis C virus and metabolic disorder interactions towards liver damage and
      atherosclerosis.
AB  - Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and
      alterations of glucose metabolism have reached pandemic proportions in western
      countries. However, the frequent coexistence between these two conditions is more
      than simply coincidental, since HCV can induce insulin resistance through several
      mechanisms. Indeed, the virus interferes with insulin signaling both directly and
      indirectly, inducing the production of pro-inflammatory cytokines. Furthermore,
      the entire viral life cycle has strict interconnections with lipid metabolism,
      and HCV is responsible for a "viral" steatosis which is frequently superimposed
      to a "metabolic" one. Several evidences suggest that HCV-induced metabolic
      disorders contribute both to the evolution of liver fibrosis and, likely, to the
      progression of the other disorders which are typically associated with altered
      metabolism, in particular atherosclerosis. In the present review, we will examine
      in depth the links between HCV infection and insulin resistance, liver steatosis
      and diabetes, and analyze the impact of these interactions on the progression of
      liver fibrosis and atherosclerosis. Special attention will be focused on the
      highly debated topic of the relationship between HCV infection and cardiovascular
      disease. The available clinical literature on this item will be broadly reviewed
      and all the mechanisms possibly implied will be discussed. 

PMID- 24659876
TI  - Individualization of chronic hepatitis C treatment according to the host
      characteristics.
AB  - Hepatitis C virus (HCV) infection is a global health problem that affects more
      than 170 million people worldwide. It is a major cause of cirrhosis and
      hepatocellular carcinoma, making the virus the most common cause of liver failure
      and transplantation. The standard-of-care treatment for chronic hepatitis C (CHC)
      has been changed during the last decade and direct acting antiviral drugs have
      already been used. Besides, understanding of the pathogenesis of CHC has evolved
      rapidly during the last years and now several host factors are known to affect
      the natural history and response to treatment. Recent genome-wide association
      studies have shown the important role of interleukin-28B and inosine
      triphosphatase in HCV infection. The present review article attempts to summarize
      the current knowledge on the role of host factors towards individualization of
      HCV treatment. 

PMID- 24659877
TI  - Non-invasive diagnosis of liver fibrosis in chronic hepatitis C.
AB  - Assessment of liver fibrosis in chronic hepatitis C virus (HCV) infection is
      considered a relevant part of patient care and key for decision making. Although
      liver biopsy has been considered the gold standard for staging liver fibrosis, it
      is an invasive technique and subject to sampling errors and significant intra-
      and inter-observer variability. Over the last decade, several noninvasive markers
      were proposed for liver fibrosis diagnosis in chronic HCV infection, with
      variable performance. Besides the clear advantage of being noninvasive, a more
      objective interpretation of test results may overcome the mentioned intra- and
      inter-observer variability of liver biopsy. In addition, these tests can
      theoretically offer a more accurate view of fibrogenic events occurring in the
      entire liver with the advantage of providing frequent fibrosis evaluation without
      additional risk. However, in general, these tests show low accuracy in
      discriminating between intermediate stages of fibrosis and may be influenced by
      several hepatic and extra-hepatic conditions. These methods are either serum
      markers (usually combined in a mathematical model) or imaging modalities that can
      be used separately or combined in algorithms to improve accuracy. In this review
      we will discuss the different noninvasive methods that are currently available
      for the evaluation of liver fibrosis in chronic hepatitis C, their advantages,
      limitations and application in clinical practice. 

PMID- 24659878
TI  - Chronic hepatitis C genotype 1 virus: who should wait for treatment?
AB  - Elucidation of the natural history of chronic hepatitis C (CHC) and the
      identification of risk factors for its progression to advanced liver disease have
      allowed many physicians to recommend deferral treatment (triple therapy) in
      favour of waiting for new drug availability for patients who are at low risk of
      progression to significant liver disease. Newer generation drugs are currently
      under development, and are expected to feature improved efficacy and safety
      profiles, as well as less complex and shorter duration delivery regimens,
      compared to the current standards of care. In addition, patients with cirrhosis
      and prior null responders have a low rate (around 15%) of achieving sustained
      virological response (SVR) with triple therapy, and physicians must also consider
      the decision to wait for new treatments in the future for these patients as well.
      Naive patients are the most likely to achieve a close to 100% SVR rate;
      therefore, it may be advisable to recommend that patients with mild to moderate
      CHC should wait for the newer therapy options. In contrast, patients with
      advanced fibrosis and cirrhosis will be those with the greatest need for
      expedited therapeutic intervention. There remains a need, however, for
      establishing definitive clinical management guidelines to maximize the benefit of
      waiting for new drugs and minimize risk of side effects and non-response to the
      current triple therapy. 

PMID- 24659879
TI  - Hepatitis C-related liver cirrhosis - strategies for the prevention of hepatic
      decompensation, hepatocarcinogenesis, and mortality.
AB  - Liver cirrhosis (LC) is a critical stage of chronic liver disease, including that
      caused by hepatitis C virus (HCV). In the absence of antiviral therapy, 67%-91%
      of patients with HCV-related LC patients die of liver-related causes, including
      hepatocellular carcinoma (HCC) and liver failure. Among the therapeutic
      strategies used to prevent liver-related complications in these patients is
      standard therapy with pegylated interferon and ribavirin, which induces a
      sustained virological response (SVR) in 25% of HCV genotype 1-infected patients
      and in 69% of patients infected with genotypes 2 and 3. SVR in patients with HCV
      related LC has been associated with reduced rates of hepatic decompensation, HCC,
      and mortality. More recently developed direct-acting antiviral agents have shown
      excellent antiviral efficacy, with preliminary data demonstrating that an
      interferon-free regimen that includes these direct-acting antiviral agents
      achieved SVR in more than 50% of patients with HCV genotype 1 LC. Branched-chain
      amino acid supplementation, improvement of insulin resistance, and the use of
      beta-blockers for portal hypertension may also reduce liver-related
      complications. Here, we review advances in antiviral and adjunctive therapies for
      improved outcomes in patients with HCV-associated LC. 

PMID- 24659881
TI  - Hepatitis C virus NS5A inhibitors and drug resistance mutations.
AB  - Some direct-acting antiviral agents for hepatitis C virus (HCV), such as
      telaprevir and boceprevir have been available since 2011. It was reported that
      HCV NS5A is associated with interferon signaling related to HCV replication and
      hepatocarcinogenesis. HCV NS5A inhibitors efficiently inhibited HCV replication
      in vitro. Human studies showed that dual, triple and quad regimens with HCV NS5A
      inhibitors, such as daclatasvir and ledipasvir, in combination with other direct
      acting antiviral agents against other regions of HCV with or without
      peginterferon/ribavirin, could efficiently inhibit HCV replication according to
      HCV genotypes. These combinations might be a powerful tool for "difficult-to
      treat" HCV-infected patients. "First generation" HCV NS5A inhibitors such as
      daclatasvir, ledipasvir and ABT-267, which are now in phase III clinical trials,
      could result in resistance mutations. "Second generation" NS5A inhibitors such as
      GS-5816, ACH-3102, and MK-8742, have displayed improvements in the genetic
      barrier while maintaining potency. HCV NS5A inhibitors are safe at low
      concentrations, which make them attractive for use despite low genetic barriers,
      although, in fact, HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors,
      HCV NS5B inhibitors or peginterferon plus ribavirin. This review article
      describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A
      inhibitors be used in combination regimens potent enough to prevent the emergence
      of resistant variants. 

PMID- 24659880
TI  - Interaction between hepatitis C virus and metabolic factors.
AB  - Hepatitis C virus (HCV) infection disrupts the normal metabolism processes, but
      is also influenced by several of the host's metabolic factors. An obvious and
      significantly detrimental pathophysiological feature of HCV infection is insulin
      resistance in hepatic and peripheral tissues. Substantial research efforts have
      been put forth recently to elucidate the molecular mechanism of HCV-induced
      insulin resistance, and several cytokines, such as tumor necrosis factor-alpha,
      have been identified as important contributors to the development of insulin
      resistance in the distant peripheral tissues of HCV-infected patients and animal
      models. The demonstrated etiologies of HCV-induced whole-body insulin resistance
      include oxidative stress, lipid metabolism abnormalities, hepatic steatosis and
      iron overload. In addition, myriad effects of this condition have been
      characterized, including glucose intolerance, resistance to antiviral therapy,
      progression of hepatic fibrosis, development of hepatocellular carcinoma, and
      general decrease in quality of life. Metabolic-related conditions and disorders,
      such as visceral obesity and diabetes mellitus, have been shown to
      synergistically enhance HCV-induced metabolic disturbance, and are associated
      with worse prognosis. Yet, the molecular interactions between HCV-induced
      metabolic disturbance and host-associated metabolic factors remain largely
      unknown. The diet and lifestyle recommendations for chronic hepatitis C are
      basically the same as those for obesity, diabetes, and metabolic syndrome.
      Specifically, patients are suggested to restrict their dietary iron intake,
      abstain from alcohol and tobacco, and increase their intake of green tea and
      coffee (to attain the beneficial effects of caffeine and polyphenols). While
      successful clinical management of HCV-infected patients with metabolic disorders
      has also been achieved with some anti-diabetic (i.e., metformin) and anti-lipid
      (i.e., statins) medications, it is recommended that sulfonylurea and insulin be
      avoided. 

PMID- 24659882
TI  - Understanding the interaction of hepatitis C virus with host DEAD-box RNA
      helicases.
AB  - The current therapeutic regimen to combat chronic hepatitis C is not optimal due
      to substantial side effects and the failure of a significant proportion of
      patients to achieve a sustained virological response. Recently developed direct
      acting antivirals targeting hepatitis C virus (HCV) enzymes reportedly increase
      the virologic response to therapy but may lead to a selection of drug-resistant
      variants. Besides direct-acting antivirals, another promising class of HCV drugs
      in development include host targeting agents that are responsible for interfering
      with the host factors crucial for the viral life cycle. A family of host proteins
      known as DEAD-box RNA helicases, characterized by nine conserved motifs, is known
      to play an important role in RNA metabolism. Several members of this family such
      as DDX3, DDX5 and DDX6 have been shown to play a role in HCV replication and this
      review will summarize our current knowledge on their interaction with HCV. As
      chronic hepatitis C is one of the leading causes of hepatocellular carcinoma, the
      involvement of DEAD-box RNA helicases in the development of HCC will also be
      highlighted. Continuing research on the interaction of host DEAD-box proteins
      with HCV and the contribution to viral replication and pathogenesis could be the
      panacea for the development of novel therapeutics against HCV. 

PMID- 24659884
TI  - Medicinal plants against hepatitis C virus.
AB  - Hepatitis C virus (HCV) is a global health concern which is responsible for most
      of the liver diseases. Currently, there is no vaccine available for prevention of
      HCV infection due to the high degree of strain variation. The current standard of
      care is a combination of pegylated interferon alpha with ribavirin and
      boceprevir/telaprevir. This treatment was partially effective and had significant
      side effects. Hence, there is a need to develop new antiviral agents that
      interfere with different stages of the HCV life cycle. Recent advances in the
      understanding of both the cellular and molecular mechanisms of HCV replication
      have provided the basis for novel therapeutic strategies. Several hundred plant
      species and their phyto-constituents have been isolated for screening against
      HCV, and some have been shown to have great medicinal value in preventing and/or
      ameliorating viral diseases in pre-clinical and clinical trials. This review
      summarizes medicinal plants and their phytochemicals which inhibit different
      stages of HCV life cycle and discuss their potential use in HCV therapy. 

PMID- 24659883
TI  - Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and
      clinical implication.
AB  - Hepatitis C virus (HCV) is a serious public health problem affecting 170 million
      carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and
      liver cancer and is the primary cause for liver transplantation worldwide. HCV
      genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also
      occasionally found in migrant patients from endemic countries. HCV-6 has
      considerable genetic diversity with 23 subtypes (a to w). Although direct
      sequencing followed by phylogenetic analysis is the gold standard for HCV-6
      genotyping and subtyping, there are also now rapid genotyping tests available
      such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics,
      Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations
      as patients infected with other genotypes. Based on current evidence, the optimal
      treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk,
      although a shortened treatment duration of 24 wk could be sufficient in patients
      with low pretreatment viral load who achieve rapid virological response. In
      addition, the development of direct-acting antiviral agents is ongoing, and they
      give high response rate when combined with standard therapy. Herein, we review
      the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.

PMID- 24659885
TI  - Current testing strategies for hepatitis C virus infection in blood donors and
      the way forward.
AB  - Screening tests for blood donations are based upon sensitivity, cost
      effectiveness and their suitability for high-throughput testing. Enzyme
      immunoassay (EIAs) for hepatitis C virus (HCV) antibodies were the initial
      screening tests introduced. The "first generation" antibody EIAs detected
      seroconversion after unduly long infectious window period. Improved HCV antibody
      assays still had an infectious window period around 66 d. HCV core antigen EIAs
      shortened the window period considerably, but high costs did not lead to
      widespread acceptance. A fourth-generation HCV antigen and antibody assay
      (combination EIA) is more convenient as two infectious markers of HCV are
      detected in the same assay. Molecular testing for HCV-RNA utilizing nucleic acid
      amplification technology (NAT) is the most sensitive assay and shortens the
      window period to only 4 d. Implementation of NAT in many developed countries
      around the world has resulted in dramatic reductions in transfusion transmissible
      HCV and relative risk is now < 1 per million donations. However, HCV serology
      still continues to be retained as some donations are serology positive but NAT
      negative. In resource constrained countries HCV screening is highly variable,
      depending upon infrastructure, trained manpower and financial resource. Rapid
      tests which do not require instrumentation and are simple to perform are used in
      many small and remotely located blood centres. The sensitivity as compared to
      EIAs is less and wherever feasible HCV antibody EIAs are most frequently used
      screening assays. Efforts have been made to implement combined antigen-antibody
      assays and even NAT in some of these countries. 

PMID- 24659886
TI  - Updates on the treatment and outcomes of dual chronic hepatitis C and B virus
      infection.
AB  - Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is found in HBV or
      HCV endemic areas, and in specific populations exhibiting a high risk of
      parenteral viral transmission. Clinical observations have revealed that HCV/HBV
      dually infected patients demonstrate a higher risk of liver disease progression
      compared with HBV or HCV monoinfected patients. The viral activity responsible
      for liver disease progression can be determined by examining the viral loads of
      HCV and HBV and by conducting liver biopsy examinations. Recent trials have
      confirmed that the combination therapy of peginterferon alpha-2a or 2b and
      ribavirin for dual hepatitis patients with HCV dominance appears to be as
      effective and safe as it is in patients with HCV monoinfections. Strikingly,
      approximately 60% of dually infected patients with inactive hepatitis B before
      treatment develop HBV reactivation after the clearance of the HCV. The clinical
      significance of this HBV reactivation and the strategy to prevent and treat this
      event should be determined. Furthermore, approximately 30% of dually infected
      patients lost hepatitis B surface antigen (HBsAg) within 5 years after the start
      of peginterferon-based therapy, and 40% of them harbored occult HBV infection.
      The underlying mechanisms of their accelerating HBsAg seroclearance and the
      development of occult HBV await further investigations. Moreover, the optimal
      treatment strategies for dually infected patients who are seropositive for the
      hepatitis B e antigen must be explored. Finally, the advent of new direct-acting
      antiviral-based anti-HCV therapy may change the optimal therapies for patients
      with dual hepatitis in the near future, which warrants further clinical trials. 

PMID- 24659887
TI  - Useful biomarkers for assessment of hepatitis C virus infection-associated
      autoimmune disorders.
AB  - During the course of chronic hepatitis C virus (HCV) infection, various
      extrahepatic manifestations of autoimmune disorders may occur, including
      arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid
      dysfunction. In addition, the prevalence of circulating autoantibodies is high
      among patients with HCV infection. Commonly detected autoantibodies in HCV
      infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti
      SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth
      muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies
      may be associated with underlying autoimmune disorders or liver inflammation in
      HCV infection. A possible reason for antibody production is overactivation and
      proliferation of B lymphocytes, via the interaction with the surface protein of
      HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis
      of HCV-related autoimmune symptoms as primary autoimmune disorders should be
      avoided. This review describes biomarkers that are useful in clinically
      evaluating autoimmune manifestations and disorders associated with HCV infection.

PMID- 24659888
TI  - Host RNA circles and the origin of hepatitis delta virus.
AB  - Recent reports show that many cellular RNAs are processed to form circular
      species that are relatively abundant and resistant to host nucleases. In some
      cases, such circles actually bind host microRNAs. Such depletion of available
      microRNAs appears to have biological roles; for instance, in homeostasis and
      disease. These findings regarding host RNA circles support a speculative
      reappraisal of the origin and mode of replication of hepatitis delta virus,
      hepatitis delta virus (HDV), an agent with a small circular RNA genome;
      specifically, it is proposed that in hepatocytes infected with hepatitis B virus
      (HBV), some viral RNA species are processed to circular forms, which by a series
      of chance events lead to an RNA that can be both replicated by host enzymes and
      assembled, using HBV envelope proteins, to form particles some of which are
      infectious. Such a model also may provide some new insights into the potential
      pathogenic potential of HDV infections. In return, new insights into HDV might
      provide information leading to a better understanding of the roles of the host
      RNA circles. 

PMID- 24659889
TI  - Differential gene expression of chemokines in KRAS and BRAF mutated colorectal
      cell lines: role of cytokines.
AB  - AIM: To study KRAS/BRAF mutations in colorectal-cancer (CRC) that influences the
      efficacy of treatment. To develop strategies for overcoming combination of
      treatment. METHODS: Five colonic cell-lines were investigated: DLD-1 with KRAS
      (G13D) mutation, HT 29 and Colo 205 with BRAF (V600E) mutation as well as the
      wild type (Wt) cell-lines Caco2 and Colo-320. DLD-1 (KRAS), HT-29 (BRAF) and
      Caco2 (Wt) cell lines were treated with cytokines (TNFalpha 50 ng, IL-1beta 1 ng
      and IFNgamma 50 ng) and harvested at different time points (1-24 h). KRAS
      inhibition was performed by the siRNA-approach. Two colorectal cancer cells DLD-1
      and Caco2 were used for KRAS inhibition. About 70% confluency were confirmed
      before transfection with small interferring RNA (siRNA) oligonucleotides. All the
      synthetic siRNA sequences were designed in our laboratory. Total RNA and protein
      was isolated from the cells for RT-PCR and Western blotting. Densitometry of the
      Western blotting was analyzed with the Image J software (NIH). Results are shown
      as mean +/- SD. RESULTS: RT-PCR analysis in non-stimulated cells showed a low
      basal expression of TNFalpha and IL-1beta in the DLD-1 KRAS-mutated cell-line,
      compared to Caco2 wild type. No detection was found for IL-6 and IFNgamma in any
      of the studied cell lines. In contrast, pro-angiogenic chemokines (CXCL1, CXCL8)
      showed a high constitutive expression in the mutated cell-lines DLD-1 (KRAS), HT
      29 and Colo205 (BRAF), compared to wild type (Caco2). The anti-angiogenic
      chemokine (CXCL10) showed a high basal expression in wild-type, compared to
      mutated cell-lines. KRAS down-regulation by siRNA showed a significant decrease
      in CXCL1 and CXCL10 gene expression in the DLD-1 (KRAS) cell-line in comparison
      to wild type (Caco2) at 72 h after KRAS silencing. In contrast, the specific KRAS
      inhibition resulted in an up-regulation of CXCL1 and CXCL10. The results of our
      study show a higher expression of pro-angiogenic chemokines at basal level in
      mutated cell-lines, which was further increased by cytokine treatment.
      CONCLUSION: To summarize, basal chemokine gene expression for pro-angiogenic
      chemokines was high in mutated as compared to wild type cell-lines. This reflects
      the likely existence of a different microenvironment in tumours consistent of
      wild type or mutated cells. This may help to rationalize the choice of molecular
      targets for suitable therapeutic investigation in clinical studies.

PMID- 24659890
TI  - Frequency and prognostic role of mucosal healing in patients with Crohn's disease
      and ulcerative colitis after one-year of biological therapy.
AB  - AIM: To assess the endoscopic activity before and after a one-year period of
      biological therapy and to evaluate the frequency of relapses and need for
      retreatment after stopping the biologicals in patients with Crohn's disease (CD)
      and ulcerative colitis (UC). METHODS: The data from 41 patients with CD and 22
      patients with UC were assessed. Twenty-four CD patients received infliximab, and
      17 received adalimumab. The endoscopic severity of CD was quantified with the
      simplified endoscopic activity score for Crohn's disease in CD and with the Mayo
      endoscopic subscore in UC. RESULTS: Mucosal healing was achieved in 23 CD and 7
      UC patients. Biological therapy had to be restarted in 78% of patients achieving
      complete mucosal healing with CD and in 100% of patients with UC. Neither
      clinical remission nor mucosal healing was associated with the time to restarting
      the biological therapy in either CD or UC. CONCLUSION: Mucosal healing did not
      predict sustained clinical remission in patients in whom the biological therapies
      had been stopped.

PMID- 24659891
TI  - A randomized trial of iron depletion in patients with nonalcoholic fatty liver
      disease and hyperferritinemia.
AB  - AIM: To compare iron depletion to lifestyle changes alone in patients with severe
      nonalcoholic fatty liver disease (NAFLD) and hyperferritinemia, a frequent
      feature associated with more severe liver damage, despite at least 6 mo of
      lifestyle changes. METHODS: Eligible subjects had to be 18-75 years old who
      underwent liver biopsy for ultrasonographically detected liver steatosis and
      hyperferritinemia, ferritin levels >= 250 ng/mL, and NAFLD activity score > 1.
      Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d
      according to baseline hemoglobin values and venesection tolerance, until ferritin
      < 30 ng/mL and/or transferrin saturation (TS) < 25%. Thirty-eight patients were
      randomized 1:1 to phlebotomy (n = 21) or lifestyle changes alone (n = 17). The
      main outcome of the study was improvement in liver damage according to the NAFLD
      activity score at 2 years, secondary outcomes were improvements in liver enzymes
      [alanine aminotransferases (ALT), aspartate aminotransferase (AST), and gamma
      glutamyl-transferases (GGT)]. RESULTS: Phlebotomy was associated with
      normalization of iron parameters without adverse events. In the 21 patients
      compliant to the study protocol, the rate of histological improvement was higher
      in iron depleted vs control subjects (8/12, 67% vs 2/9, 22%, P = 0.039). There
      was a better improvement in steatosis grade in iron depleted vs control patients
      (P = 0.02). In patients followed-up at two years (n = 35), ALT, AST, and GGT
      levels were lower in iron-depleted than in control patients (P < 0.05). The
      prevalence of subjects with improvement in histological damage or, in the absence
      of liver biopsy, ALT decrease >= 20% (associated with histological improvement in
      biopsied patients) was higher in the phlebotomy than in the control arm (P =
      0.022). The effect of iron depletion on liver damage improvement as assessed by
      histology or ALT decrease >= 20% was independent of baseline AST/ALT ratio and
      insulin resistance (P = 0.0001). CONCLUSION: Iron depletion by phlebotomy is
      likely associated with a higher rate of improvement of histological liver damage
      than lifestyle changes alone in patients with NAFLD and hyperferritinemia, and
      with amelioration of liver enzymes.

PMID- 24659892
TI  - Hyperoxia accelerates progression of hepatic fibrosis by up-regulation of
      transforming growth factor-beta expression.
AB  - AIM: To investigate the effect of hypoxia or hyperoxia on the progression of
      hepatic fibrosis and to examine the role of transforming growth factor-beta (TGF
      beta) in the livers of rats exposed to hypoxic or hyperoxic conditions. METHODS:
      Male Sprague-Dawley rats were injected intraperitoneally with thioacetamide to
      induce hepatic fibrosis and were randomly divided into a hypoxia group, a
      hyperoxia group and an untreated control group. Ten rats in the hypoxia group
      were exposed to an altitude of 20000 ft for 1 h/d during 7 wk. Ten rats in the
      hyperoxia group were exposed to a water depth of 20 m with 100% oxygen supply for
      1 h/d during 7 wk. We evaluated the degree of hepatic fibrosis using Masson
      trichrome stain and examined the expression level of hepatic TGF-beta mRNA using
      quantitative real-time reverse transcriptase-polymerase chain reaction analysis.
      RESULTS: Eight of 10 rats exposed to hypoxia showed diffuse and confluent
      fibrosis with the formation of structurally abnormal parenchymal nodules
      involving the entire liver, consistent with hepatic cirrhosis. Nine of 10 rats
      exposed to hyperoxia also demonstrated obvious histological findings of hepatic
      cirrhosis identical to those in hypoxic rat livers. In contrast, 8 of 10
      untreated rats had periportal or septal fibrosis only. The frequency of hepatic
      cirrhosis in hypoxic rats (P = 0.009) and hyperoxic rats (P = 0.003) was
      significantly higher than that in untreated rats. In addition, hepatic TGF-beta
      mRNA levels in hyperoxic rats were significantly higher than those in untreated
      rats. The mean value of the normalized TGF-beta mRNA/beta-actin expression ratio
      in the hyperoxic rats was 1.9-fold higher than that in the untreated rats (P =
      0.027). CONCLUSION: We demonstrated that both hypoxia and hyperoxia accelerated
      the progression of hepatic fibrosis in rats. Significant up-regulation of hepatic
      TGF-beta in hyperoxic rats suggests that TGF-beta is involved in the acceleration
      of hepatic fibrosis under hyperoxic conditions.

PMID- 24659893
TI  - Midkine promotes perineural invasion in human pancreatic cancer.
AB  - AIM: To investigate midkine (MK) and syndecan-3 protein expression in pancreatic
      cancer by immunohistochemistry, and to analyze their correlation with
      clinicopathological features, perineural invasion, and prognosis. METHODS:
      Pancreatic cancer tissues (including adequately sized tumor tissue samples and
      tissue samples taken from areas less than 2.0 cm around the tumor) were taken
      from 42 patients who were undergoing a partial duodenopancreatectomy. MK and
      syndecan-3 proteins were detected by immunohistochemistry using a standardized
      streptavidin-peroxidase method, and analyzed for their correlation with
      clinicopathological features, perineural invasion, and prognosis. Associations of
      neural invasion with aggressive characteristics of pancreatic cancer and the
      presence of perineural invasion were assessed by two independent observers
      blinded to the patient status. RESULTS: MK and syndecan-3 were found in 26
      (61.9%) and 24 (57.1%) specimens, respectively. MK and syndecan-3 expression was
      associated with perineural invasion (P = 0.018 and 0.031, respectively). High MK
      expression was closely associated with advanced tumor, node and metastasis stage
      (P = 0.008), lymph node metastasis (P = 0.042), and decreased postoperative
      survival at 3 years (51.0% vs 21.8%, P = 0.001). Syndecan-3 levels were
      correlated with tumor size (P = 0.028). Patients who were syndecan-3 negative had
      a higher cumulative survival rate than those who were positive, but the
      difference was not significant (44.0% vs 23.0%, P > 0.05). CONCLUSION: MK and
      syndecan-3 are frequently expressed in pancreatic cancer and associated with
      perineural invasion. High expression of MK and syndecan-3 may contribute to the
      highly perineural invasion and poor prognosis of human pancreatic cancer.

PMID- 24659894
TI  - Mass spectrometry-based serum peptide profiling in hepatocellular carcinoma with
      bone metastasis.
AB  - AIM: To investigate the potential of serum peptides as a diagnostic tool for
      hepatocellular carcinoma (HCC) with bone metastasis. METHODS: Matrix-assisted
      laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) was
      used to characterize the serum peptide profile of HCC patients with bone
      metastasis. Serum samples from 138 HCC patients (66 cases with and 72 cases
      without bone metastasis) were randomly assigned into a training set (n = 76) and
      a test set (n = 62). Differential serum peptides were examined using ClinProt
      magnetic bead-based purification followed by MALDI-TOF-MS. The sequences of
      differentially expressed serum peptides were identified using liquid
      chromatography-mass spectrometry. A diagnostic model was established using a
      learning algorithm of radial basis function neural network verified by a single
      blind trial. Receiver operating characteristic (ROC) analysis was performed to
      evaluate the diagnostic power of the established model. RESULTS: Ten peptide
      peaks were significantly different between HCC patients with or without bone
      metastasis (P < 0.001). Sequences of seven peptides with mass to charge ratios
      (m/z) of 1780.7, 1866.5, 2131.6, 2880.4, 1532.4, 2489.8, and 2234.3 were
      successfully identified. These seven peptides were derived from alpha
      fetoprotein, prothrombin, serglycin, isoform 2 of inter-alpha-trypsin inhibitor
      heavy chain H4, isoform 1 of autophagy-related protein 16-2, and transthyretin
      and fibrinogen beta chains, respectively. The recognition rate and predictive
      power of a diagnostic model established on the basis of six significant peptides
      (m/z for these six peptides were 1535.4, 1780.7, 1866.5, 2131.6, 2880.4, and
      2901.9) were 89.47% and 82.89%, respectively. The sensitivity and specificity of
      this model based upon a single blind trial were 85.29% and 85.71%, respectively.
      ROC analysis found that the AUC (area under the ROC curve) value was 0.911.
      CONCLUSION: Our study suggested that serum peptides may serve as a diagnosis tool
      for HCC bone metastasis.

PMID- 24659895
TI  - Reappraisal of xenobiotic-induced, oxidative stress-mediated cellular injury in
      chronic pancreatitis: a systematic review.
AB  - AIM: To reappraise the hypothesis of xenobiotic induced, cytochrome P450
      mediated, micronutrient-deficient oxidative injury in chronic pancreatitis.
      METHODS: Individual searches of the Medline and Embase databases were conducted
      for each component of the theory of oxidative-stress mediated cellular injury for
      the period from 1(st) January 1990 to 31(st) December 2012 using appropriate
      medical subject headings. Boolean operators were used. The individual components
      were drawn from a recent update on theory of oxidative stress-mediated cellular
      injury in chronic pancreatitis. RESULTS: In relation to the association between
      exposure to volatile hydrocarbons and chronic pancreatitis the studies fail to
      adequately control for alcohol intake. Cytochrome P450 (CYP) induction occurs as
      a diffuse hepatic and extra-hepatic response to xenobiotic exposure rather than
      an acinar cell-specific process. GSH depletion is not consistently confirmed.
      There is good evidence of superoxide dismutase depletion in acute phases of
      injury but less to support a chronic intra-acinar depletion. Although the liver
      is the principal site of CYP induction there is no evidence to suggest that
      oxidative by-products are carried in bile and reflux into the pancreatic duct to
      cause injury. CONCLUSION: Pancreatic acinar cell injury due to short-lived oxygen
      free radicals (generated by injury mediated by prematurely activated intra-acinar
      trypsin) is an important mechanism of cell damage in chronic pancreatitis.
      However, in contemporary paradigms of chronic pancreatitis this should be seen as
      one of a series of cell-injury mechanisms rather than a sole mediator.

PMID- 24659896
TI  - Acute hepatitis B of genotype H resulting in persistent infection.
AB  - A 47-year-old man presented with general fatigue and dark urine. The laboratory
      data showed increased levels of hepatic transaminases. The patient was positive
      for hepatitis B virus (HBV) markers and negative for anti-human immunodeficiency
      virus. The HBV-DNA titer was set to 7.7 log copies/mL. The patient was diagnosed
      with acute hepatitis B. The HBV infection route was obscure. The serum levels of
      hepatic transaminases decreased to normal ranges without any treatment, but the
      HBV-DNA status was maintained for at least 26 mo, indicating the presence of
      persistent infection. We isolated HBV from the acute-phase serum and determined
      the genome sequence. A phylogenetic analysis revealed that the isolated HBV was
      genotype H. In this patient, the elevated peak level of HBV-DNA and the risk
      alleles at human genome single nucleotide polymorphisms s3077 and rs9277535 in
      the human leukocyte antigen-DP locus were considered to be risk factors for
      chronic infection. This case suggests that there is a risk of persistent
      infection by HBV genotype H following acute hepatitis; further cases of HBV
      genotype H infection must be identified and characterized. Thus, the complete
      determination of the HBV genotype may be essential during routine clinical care
      of acute hepatitis B outpatients. 

PMID- 24659897
TI  - Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia
      site.
AB  - Extrahepatic bile duct (EHBD) cancer may occur metachronously, and these cancers
      are resectable with a favorable prognosis. We aimed to identify the pattern of
      metachronous EHBD cancer. We classified the cases of metachronous EHBD cancer
      reported in the literature thus far and investigated two new cases of
      metachronous EHBD cancer. A 70-year-old female underwent R0 bile duct resection
      for a type 1 Klatskin tumor (pT1N0M0). A 70-year-old male patient underwent R0
      bile duct resection for a middle bile duct cancer (pT2N1M0). Imaging studies of
      both patients taken at 14 and 24 mo after first surgery respectively revealed a
      metachronous cholangiocarcinoma that required pancreaticoduodenectomy (PD).
      Histopathology of the both tumors after PD revealed cholangiocarcinoma invading
      the pancreas (pT3N0M0). Both patients have been free from recurrence for 6 years
      and 16 mo respectively after the second surgery. Through a review of the
      literature on these cases, we classified the pattern of metachronous EHBD cancer
      according to the site of de novo neoplasia. The proximal remnant bile duct was
      most commonly involved. Metachronous EHBD cancer should be distinguished from an
      unresectable recurrent tumor. Classifying metachronous EHBD cancer may be helpful
      in identifying rare metachronous tumors. 

PMID- 24659898
TI  - Valsalva retinopathy following esophagogastroduodenoscopy under propofol
      sedation: a case report.
AB  - We report a case of Valsalva retinopathy associated with
      esophagogastroduodenoscopy (EGD) under propofol sedation. A 43-year-old woman who
      had no previous history of systemic or ocular disease presented with a complaint
      of decreased vision in her left eye, which developed one day after EGD under
      propofol sedation. According to the referring physician, the patient had
      experienced multiple sustained Valsalva maneuvers during EGD. The fundus
      examination of the left eye showed a large preretinal hemorrhage surrounded by
      multiple small retinal hemorrhages in the posterior pole. One month later, fundus
      examination revealed a floating organized vitreous hemorrhage. The pars plana
      vitrectomy was performed to treat persistent vitreous hemorrhage. One month after
      vitrectomy, fundus examination showed normal retina and the patient's vision
      recovered to 20/20. Valsalva maneuver can occur during EGD under sedation, and
      Valsalva retinopathy should be considered as a possible cause. Valsalva
      retinopathy should be included in the differential diagnosis when a patient
      complains of blurred vision following EGD. 

PMID- 24659899
TI  - Predicting reading outcomes with progress monitoring slopes among middle grade
      students.
AB  - Effective implementation of response-to-intervention (RTI) frameworks depends on
      efficient tools for monitoring progress. Evaluations of growth (i.e., slope) may
      be less efficient than evaluations of status at a single time point, especially
      if slopes do not add to predictions of outcomes over status. We examined progress
      monitoring slope validity for predicting reading outcomes among middle school
      students by evaluating latent growth models for different progress monitoring
      measure-outcome combinations. We used multi-group modeling to evaluate the
      effects of reading ability, reading intervention, and progress monitoring
      administration condition on slope validity. Slope validity was greatest when
      progress monitoring was aligned with the outcome (i.e., word reading fluency
      slope was used to predict fluency outcomes in contrast to comprehension
      outcomes), but effects varied across administration conditions (viz., repeated
      reading of familiar vs. novel passages). Unless the progress monitoring measure
      is highly aligned with outcome, slope may be an inefficient method for evaluating
      progress in an RTI context.

PMID- 24659900
TI  - The Parental Concerns Questionnaire: A Brief Screening Instrument for Potentially
      Severe Behavior Problems in Infants and Toddlers At-Risk for Developmental
      Delays.
AB  - The Parental Concerns Questionnaire (PCQ) was designed as a parent-interview
      screening instrument for young children with developmental concerns at risk for
      potentially severe behavior problems (SBDs). Parents of 262 young children (4 to
      48 months) answered to the 15 dichotomous PCQ items interviewed by trained staff.
      Cluster analysis for items revealed three item clusters, which we labeled
      Developmental/Social (8 items), Biomedical (3 items), and Behavior Problems (3
      items). This paper discussed primarily the Behavior Problems cluster, with items
      referring to self-injurious, aggressive, and destructive behaviors. Parents'
      concerns about behavior problems were high, with item-endorsements of the
      Behavior Problems cluster ranging from 41.8 % to 68.8 %. The Behavior Problems
      cluster was significantly correlated with all three subscales of the Behavior
      Problems Inventory (BPI-01), with select subscales of the Aberrant Behavior
      Checklist (ABC), and with the Repetitive Behavior Scale-Revised (RBS-R) providing
      some evidence for concurrent validity. Sensitivity and specificity data were
      computed for the three PCQ items as well as for the cluster score in comparison
      with the BPI-01, ABC, and RBS-R showing strong sensitivity. The PCQ Behavior
      Problems cluster is a useful screening checklist with high sensitivity for
      potential SBDs in young children at-risk for developmental delays.

PMID- 24659901
TI  - A Liberal Account of Addiction.
AB  - Philosophers and psychologists have been attracted to two differing accounts of
      addictive motivation. In this paper, we investigate these two accounts and
      challenge their mutual claim that addictions compromise a person's self-control.
      First, we identify some incompatibilities between this claim of reduced self
      control and the available evidence from various disciplines. A critical
      assessment of the evidence weakens the empirical argument for reduced autonomy.
      Second, we identify sources of unwarranted normative bias in the popular theories
      of addiction that introduce systematic errors in interpreting the evidence. By
      eliminating these errors, we are able to generate a minimal, but correct account,
      of addiction that presumes addicts to be autonomous in their addictive behavior,
      absent further evidence to the contrary. Finally, we explore some of the
      implications of this minimal, correct view.

PMID- 24659902
TI  - Gender Disparities in the Mental Health of Urban Survivors of Trauma.
AB  - Women who experience traumatic events are at higher risk for mental health
      problems compared to men; however, gaps remain in our understanding of this
      disparity. A sample of 170 urban adults completed self-report measures. Women
      were significantly more likely to experience sexual assault and domestic violence
      compared to men, and they were significantly less likely to experience a robbery
      or mugging, being threatened with a weapon, or witnessing a death or assault
      compared to men. Also, women were more likely than men to meet criteria for
      probable post-traumatic stress disorder (PTSD) and depression after controlling
      for covariates and trauma level. Our findings suggest a possible differential
      vulnerability to the development of PTSD and depressive symptoms in women.

PMID- 24659903
TI  - How Children Report True and Fabricated Stressful and Non-Stressful Events.
AB  - As children can be victims or witnesses to crimes and may be required to testify
      about their experiences in court, the ability to differentiate between children's
      true and fabricated accounts of victimization is an important issue. This study
      used automated linguistic analysis software to detect linguistic patterns in
      order to differentiate between children's true and false stressful bullying
      reports and reports of non-stressful events. Results revealed that children
      displayed different linguistic patterns when reporting true and false stressful
      and non-stressful stories, with non-stressful stories being more accurately
      discriminated based on linguistic patterns. Results suggest that it is difficult
      to discriminate accurately and consistently between children's true and false
      stories of victimization.

PMID- 24659904
TI  - Genetic mapping, synteny, and physical location of two loci for Fusarium
      oxysporum f. sp. tracheiphilum race 4 resistance in cowpea [Vignaunguiculata (L.)
      Walp].
AB  - Fusarium wilt is a vascular disease caused by the fungus Fusariumoxysporum f.sp.
      tracheiphilum (Fot) in cowpea [Vignaunguiculata (L.) Walp]. In this study, we
      mapped loci conferring resistance to Fot race 4 in three cowpea RIL populations:
      IT93K-503-1 * CB46, CB27 * 24-125B-1, and CB27 * IT82E-18/Big Buff. Two
      independent loci which confer resistance to Fot race 4 were identified, Fot4-1
      and Fot4-2. Fot4-1 was identified in the IT93K-503-1 (resistant) * CB46
      (susceptible) population and was positioned on the cowpea consensus genetic map,
      spanning 21.57-29.40 cM on linkage group 5. The Fot4-2 locus was validated by
      identifying it in both the CB27 (resistant) * 24-125B-1 (susceptible) and CB27
      (resistant) * IT82E-18/Big Buff (susceptible) populations. Fot4-2 was positioned
      on the cowpea consensus genetic map on linkage group 3; the minimum distance
      spanned 71.52-71.75 cM whereas the maximum distance spanned 64.44-80.23 cM. These
      genomic locations of Fot4-1 and Fot4-2 on the cowpea consensus genetic map,
      relative to Fot3-1 which was previously identified as the locus conferring
      resistance to Fot race 3, established that all three loci were independent. The
      Fot4-1 and Fot4-2 syntenic loci were examined in Glycine max, where several
      disease-resistance candidate genes were identified for both loci. In addition,
      Fot4-1 and Fot4-2 were coarsely positioned on the cowpea physical map. Fot4-1 and
      Fot4-2 will contribute to molecular marker development for future use in marker
      assisted selection, thereby expediting introgression of Fot race 4 resistance
      into future cowpea cultivars.

PMID- 24659905
TI  - The effects of the photoperiod-insensitive alleles, se13, hd1 and ghd7, on yield
      components in rice.
AB  - Flowering time is closely associated with grain yield in rice (Oryza sativa L.).
      In temperate regions, seasonal changes in day length (known as the photoperiod)
      are an important environmental cue for floral initiation. The timing of flowering
      is important not only for successful reproduction, but also for determining the
      ideal balance between vegetative growth and reproductive growth duration. Recent
      molecular genetics studies have revealed key flowering time genes responsible for
      photoperiod sensitivity. In this study, we investigated the effect of three
      recessive photoperiod-insensitive alleles, se13, hd1 and ghd7, on yield
      components in rice under Ehd1-deficient genetic background conditions to ensure
      vegetative growth of each line. We found that se13-bearing plants had fewer
      panicles, hd1-bearing plants showed decreased grain-filling percentage, and ghd7
      bearing plants appeared to have fewer grains per panicle and fewer secondary
      branches. Our results indicate that the pleiotropic effects of photoperiod
      insensitive genes on yield components are independent of short vegetative growth.
      This will provide critical information which can be used to create photoperiod
      insensitive varieties that can be adapted to a wide range of latitudes.

PMID- 24659906
TI  - Genetics of pre-harvest sprouting resistance in a cross of Canadian adapted durum
      wheat genotypes.
AB  - Severe losses attributable to pre-harvest sprouting (PHS) have been reported in
      Canada in recent years. The genetics of PHS resistance have been more extensively
      studied in hexaploid wheat and generally not using combinations of elite
      agronomic parents. The objective of our research was to understand the genetic
      nature of PHS resistance in an elite durum cross. A doubled haploid (DH)
      population and checks were phenotyped in replicated trials for grain yield and
      PHS traits over 3 years in western Canada. The response of intact spikes to
      sprouting conditions, sampled over two development time points, was measured in a
      rain simulation chamber. The DH population was genotyped with simple sequence
      repeat and Diversity Arrays Technology markers. Genotypes were a significant
      source of variation for grain yield and PHS resistance traits in each tested
      environment. Transgressive segregant DH genotypes were identified for grain yield
      and PHS resistance measurements. Low or no correlation was detected between grain
      yield and PHS, while correlation between PHS resistance measurements was
      moderate. The heritability of PHS resistance was moderate and higher than grain
      yield. Significant quantitative trait loci with small effect were detected on
      chromosomes 1A, 1B, 5B, 7A and 7B. Both parents contributed to the PHS
      resistance. Promising DH genotypes with high and stable grain yield as well as
      PHS resistance were identified, suggesting that grain yield and PHS can be
      improved simultaneously in elite genetic materials, and that these DH genotypes
      will be useful parental material for durum breeding programs.

PMID- 24659907
TI  - Rapid Room-Temperature 11C-Methylation of Arylamines with [11C]Methyl Iodide
      Promoted by Solid Inorganic Bases in DMF.
AB  - 11[C]Methyl iodide is the most widely used reagent for labeling radiotracers with
      carbon-11 (t1/2 = 20.4 min) for molecular imaging with positron emission
      tomography. However, some substrates for labeling, especially primary arylamines
      and pyrroles, are sluggishly reactive towards [11C]methyl iodide. We found that
      insoluble inorganic bases, especially Li3N or Li2O, are effective in promoting
      rapid reactions (<= 10 min) of such substrates with no-carrier-added [11C]methyl
      iodide in DMF at room temperature to give 11C-methylated products in useful
      radiochemical yields. In particular, we discovered that some primary arylamines
      in Li3N-DMF were converted into their formanilides, and that these were readily N
      methylated with [11C]methyl iodide, preceding easy basic hydrolysis to the
      desired [11C]N-methyl secondary arylamines. Use of a solid base permitted
      selective reaction at an arylamino group and in some cases also avoided
      undesirable side reaction, such as ester group hydrolysis. An ultrasound device
      proved useful to provide remote and constant agitation of the radioactive
      heterogeneous reaction mixtures, but imparted no 'ultrasound-specific' chemical
      effect.

PMID- 24659908
TI  - Environmentally Benign Lewis Acid Promoted [2+3]-Dipolar Cycloaddition Reactions
      of Nitrile Imines with Alkenes in Water.
AB  - Mild and environmentally benign Lewis acid promoted 1,3-dipolar cycloaddition
      reactions of alpha-hydrazonyl chlorides with alkenes in water are reported. These
      alpha-hydrazonyl chlorides, in the presence of Lewis acids, generate nitrile
      imines in situ which react with dipolarophiles to furnish the corresponding
      cycloaddition products. In many cases, the required times for the completion of
      the Lewis acid promoted 1,3-dipolar cycloaddition reactions in water were
      comparable to the equivalent reactions performed in an organic solvent. Analogous
      tetrahexylammonium chloride promoted 1,3-dipolar cycloaddition reactions were
      also performed. The comparison of reaction times and cycloadduct yields for the
      aforementioned 1,3-dipolar reactions in aqueous and organic media as well as the
      proposed role of the Lewis acid in the 1,3-dipolar cycloaddition reaction are
      described.

PMID- 24659909
TI  - A Modest Proposal: Prostate Biopsies and In-house Pathology Laboratories.

PMID- 24659910
TI  - Utilization trends and positive biopsy rates for prostate biopsies in the United
      States: 2005 to 2011.
AB  - This article assesses the positive biopsy rate and core sampling pattern in
      patients undergoing needle biopsy of the prostate in the United States at a
      national reference laboratory (NRL) and anatomic pathology laboratories
      integrated into urology group practices, and analyzes the relationship between
      positive biopsy rates and the number of specimen vials per biopsy. For the years
      2005 to 2011 we collected pathology data from an NRL, including number of
      urologists and urology practices referring samples, total specimen vials
      submitted for prostate biopsies, and final pathologic diagnosis for each case.
      The diagnoses were categorized as benign, malignant, prostatic intraepithelial
      neoplasia, or atypical small acinar proliferation. Over the same period, similar
      data were gathered from urology practices with in-house laboratories performing
      global pathology services (urology practice laboratories; UPLs) as identified by
      a survey of members of the Large Urology Group Practice Association. For each
      year studied, positive biopsy rate and number of specimen vials per biopsy were
      calculated in aggregate and separately for each site of service. From 2005 to
      2011, 437,937 biopsies were submitted in > 4.23 million vials (9.4 specimen
      vials/biopsy); overall positive biopsy rate was 40.3%-this was identical at both
      the NRL and UPL (P = .97). Nationally, the number of specimen vials per biopsy
      increased sharply from a mean of 8.8 during 2005 to 2008 to a mean of 10.3 from
      2009 to 2011 (difference, 1.5 specimen vials/biopsy; P = .03). For the most
      recent 3-year period (2009-2011), the difference of 0.6 specimen vials per biopsy
      between the NRL (10.0) and UPL (10.6) was not significant (P = 0.08). Positive
      biopsy rate correlated strongly (P < .01) with number of specimen vials per
      biopsy. The positive prostate biopsy rate is 40.3% and is identical across sites
      of service. Although there was a national trend toward increased specimen vials
      per biopsy from 2005 to 2011, from 2009 to 2011 there was no significant
      difference in specimen vials per biopsy across sites of service. Increased cancer
      detection rate correlated significantly with increased number of specimens
      examined. Segregation of prostate biopsy cores into 10 to 12 unique specimen
      vials has been widely adopted by urologists across sites of service. 

PMID- 24659911
TI  - Intracavitary immunotherapy and chemotherapy for upper urinary tract cancer:
      current evidence.
AB  - A review of the literature was performed to summarize current evidence regarding
      the efficacy of topical immunotherapy and chemotherapy for upper urinary tract
      urothelial cell carcinoma (UUT-UCC) in terms of post-treatment recurrence rates.
      A Medline database literature search was performed in March 2012 using the terms
      upper urinary tract, urothelial cancer, bacillus Calmette-Guerin (BCG), and
      mitomycin C. A total of 22 full-text articles were assessed for eligibility, and
      19 studies reporting the outcomes of patients who underwent immunotherapy or
      chemotherapy with curative or adjuvant intent for UUT-UCC were chosen for
      quantitative analysis. Overall, the role of immunotherapy and chemotherapy for
      UUT-UCC is not firmly established. The most established practice is the treatment
      of carcinoma in situ (CIS) with BCG, even if a significant advantage has not yet
      been proven. The use of BCG as adjuvant therapy after complete resection of
      papillary UUT-UCC has been studied less extensively, even if recurrence rates are
      not significantly different than after the treatment of CIS. Only a few reports
      describe the use of mitomycin C, making it difficult to obtain significant
      evidence. 

PMID- 24659912
TI  - The use of in vitro fertilization in the management of male infertility: what the
      urologist needs to know.
AB  - Infertility affects approximately 10% to 20% of reproductive-age couples, many of
      whom may present initially to a urologist. Some couples may be treated medically
      to increase spontaneous conception rates; however, many will require more
      aggressive management with in vitro fertilization (IVF) and/or intracytoplasmic
      sperm injection (ICSI). IVF involves ovarian stimulation, oocyte retrieval, and
      fertilization outside of the body; ICSI involves injecting one sperm into the
      oocyte to promote fertilization. Here we provide a brief overview of IVF and ICSI
      along with a discussion of the risks involved to facilitate the counseling and
      care of the infertile couple. 

PMID- 24659915
TI  - Updates in the care and management of prostate cancer: highlights from the 2013
      prostate cancer world congress, august 6-10, 2013, melbourne, australia.

PMID- 24659914
TI  - Anesthetic Challenges in Robotic-assisted Urologic Surgery.
AB  - Robotic-assisted surgery has evolved over the past two decades with constantly
      improving technology, assisting surgeons in multiple subspecialty disciplines.
      The surgical requirements of lithotomy and steep Trendelenburg positions, along
      with the creation of a pneumoperitoneum and limited access to the patient, all
      present anesthetic management challenges in urologic surgery. Patient positioning
      requirements can cause significant physiologic effects and may result in many
      complications. Good communication among team members and knowledge of the nuances
      of robotic surgery have the potential to improve patient outcomes, increase
      efficiency, and reduce surgical and anesthetic complications. 

PMID- 24659913
TI  - Short-, Intermediate-, and Long-term Quality of Life Outcomes Following Radical
      Prostatectomy for Clinically Localized Prostate Cancer.
AB  - Many clinically localized prostate cancers that are diagnosed today are low risk,
      and prevention of disease-specific mortality may only be realized decades after
      treatment. Radical prostatectomy (RP) may adversely impact health-related quality
      of life (HRQOL) by causing both transient or permanent urinary incontinence and
      erectile dysfunction. In contrast, RP may also improve HRQOL via relief of lower
      urinary tract symptoms in men suffering from these symptoms prior to surgery.
      Because the average man treated for prostate cancer has a life expectancy of
      approximately 14 years, it is imperative to consider the long-term impact of RP
      on both survival and HRQOL in treatment decision making. This comprehensive
      literature review examines short-, intermediate-, and long-term HRQOL following
      RP. In addition, the long-term results of RP are compared with other treatment
      modalities for treating clinically localized prostate cancer. 

PMID- 24659916
TI  - 47,XYY Syndrome and Male Infertility.
AB  - Men with 47,XYY syndrome present with varying physical attributes and degrees of
      infertility. A retrospective chart review was performed on a male infertility and
      genetic anomaly database. Three patients with 47,XYY were found. Each presented
      with > 2 years of infertility. All were tall with elevated body mass indices.
      Scrotal findings ranged from normal to atrophic testicles. Semen analyses
      demonstrated oligospermia and varying endocrine profiles. Because of the diverse
      phenotype and potential lack of symptoms, identification and diagnosis of men
      with 47,XYY syndrome may be difficult. We recommend careful screening of 47,XYY
      patients and referral to primary physicians for long-term follow-up for increased
      incidence of health-related comorbidities. 

PMID- 24659917
TI  - Splenogonadal fusion: an unusual case of an acute scrotum.
AB  - We highlight a case on a normal left testicle with a fibrovascular cord with
      three nodules consistent with splenic tissue. The torsed splenule demonstrated
      hemorrhage with neutrophilic infiltrate and thrombus consistent with chronic
      infarction and torsion. Splenogonadal fusion (SGF) is a rather rare entity, with
      approximately 184 cases reported in the literature. The most comprehensive review
      was that of 123 cases completed by Carragher in 1990. Since then, an additional
      61 cases have been reported in the scientific literature. We have studied these
      61 cases in detail and have included a summary of that information here. 

PMID- 24659918
TI  - More aggressive prostate cancer in elderly men.

PMID- 24659919
TI  - PSA Velocity in Risk Stratification of Prostate Cancer.

PMID- 24659921
TI  - Genetic tests for prostate cancer.

PMID- 24659920
TI  - Patient Perceptions and Shared Decisions About PSA Screening.

PMID- 24659922
TI  - Caregiver Protective Behavior, Toddler Fear and Sadness, and Toddler Cortisol
      Reactivity in Novel Contexts.
AB  - Previous research has shown that caregiver protective behavior may exacerbate
      toddler distress in specific contexts. The current study sought to extend this
      work to examine associations between these variables and toddler cortisol
      reactivity. Ninety-three 24-month-old toddlers were observed across six novel
      contexts designed to elicit distress. Toddlers were asked to give saliva samples
      at the beginning and end of the laboratory procedure. Toddler sadness, toddler
      fear, and caregiver protective behavior were coded. Results indicate that
      caregiver protective behavior accounted for the association between toddler
      sadness and cortisol reactivity where higher levels of protective behavior were
      associated with higher cortisol reactivity. The current study showed that
      caregiver protective behavior, which functions to prevent a child from
      interacting with a novel stimulus, is an important mechanism to consider when
      understanding toddler stress responses during novel contexts.

PMID- 24659923
TI  - Investigations on the use of graphite electrodes using a Hull-type growth cell
      for the electrochemically-assisted protein crystallization.
AB  - This paper describes the use of an electrochemical Hull type cell adapted for
      protein crystallization evaluating three inclination angles (45 degrees , 60
      degrees  and 90 degrees ). For optimization experiments, classical platinum wire
      electrodes were used and once the best geometry was known, they were replaced
      with 0.5 mm diameter low-cost graphite automatic pencil leads. Using Pt and
      graphite, the cell with electrodes fitted at 90 degrees  showed the most
      favorable geometry for promoting the growth of lysozyme crystals with enough size
      for protein crystallography (between 200-250 MUm in solution, and between 500-650
      MUm in gel). The crystalline quality (mosaicity and I/sigma(I) ratio) of crystals
      obtained at different current values, was studied using these graphite electrodes
      and was compared with those protein crystals grown using platinum wire electrodes
      in solution as well as in gel experiments. These studies showed that it is
      possible to efficiently substitute the platinum electrodes by the low-cost
      graphite electrodes. This cell could be a first approach to a disposable cell for
      a large-scale use of electrochemically-assisted crystal growth method.

PMID- 24659924
TI  - Probabilistically-Cued Patterns Trump Perfect Cues in Statistical Language
      Learning.
AB  - Probabilistically-cued co-occurrence relationships between word categories are
      common in natural languages but difficult to acquire. For example, in English,
      determiner-noun and auxiliary-verb dependencies both involve co-occurrence
      relationships, but determiner-noun relationships are more reliably marked by
      correlated distributional and phonological cues, and appear to be learned more
      readily. We tested whether experience with co-occurrence relationships that are
      more reliable promotes learning those that are less reliable using an artificial
      language paradigm. Prior experience with deterministically-cued contingencies did
      not promote learning of less reliably-cued structure, nor did prior experience
      with relationships instantiated in the same vocabulary. In contrast, prior
      experience with probabilistically-cued co-occurrence relationships instantiated
      in different vocabulary did enhance learning. Thus, experience with co-occurrence
      relationships sharing underlying structure but not vocabulary may be an important
      factor in learning grammatical patterns. Furthermore, experience with
      probabilistically-cued co-occurrence relationships, despite their difficultly for
      naive learners, lays an important foundation for learning novel probabilistic
      structure.

PMID- 24659925
TI  - Examining Provider Perspectives within Housing First and Traditional Programs.
AB  - Pathways' Housing First represents a radical departure from traditional programs
      that serve individuals experiencing homelessness and co-occurring psychiatric and
      substance use disorders. This paper considered two federally funded comparison
      studies of Pathways' Housing First and traditional programs to examine whether
      differences were reflected in the perspectives of frontline providers. Both
      quantitative analysis of responses to structured questions with close-ended
      responses and qualitative analysis of open-ended responses to semistructured
      questions showed that Pathways providers had greater endorsement of consumer
      values, lesser endorsement of systems values, and greater tolerance for abnormal
      behavior that did not result in harm to others than their counterparts in
      traditional programs. Comparing provider perspectives also revealed an
      "implementation paradox"; traditional providers were inhibited from engaging
      consumers in treatment and services without housing, whereas HF providers could
      focus on issues other than securing housing. As programs increasingly adopt a
      Housing First approach, implementation challenges remain due to an existing
      workforce habituated to traditional services.

PMID- 24659926
TI  - Taking into Account the Ion-induced Dipole Interaction in the Nonbonded Model of
      Ions.
AB  - Metal ions exist in almost half of the proteins in the protein databank and they
      serve as structural, electron-transfer and catalytic elements in the metabolic
      processes of organisms. Molecular Dynamics (MD) simulation is a powerful tool
      that provides information about biomolecular systems at the atomic level. Coupled
      with the growth in computing power, algorithms like the Particle Mesh Ewald (PME)
      method have become the accepted standard when dealing with long-range
      interactions in MD simulations. The nonbonded model of metal ions consists of an
      electrostatic plus 12-6 Lennard Jones (LJ) potential and is used largely because
      of its speed relative to more accurate models. In previous work we found that
      ideal parameters do not exist that reproduce several experimental properties for
      M(II) ions simultaneously using the nonbonded model coupled with the PME method
      due to the underestimation of metal ion-ligand interactions. Via a consideration
      of the nature of the nonbonded model, we proposed that the observed error largely
      arises from overlooking charge-induced dipole interactions. The electrostatic
      plus 12-6 LJ potential model works reasonably well for neutral systems but does
      struggle with more highly charged systems. In the present work we designed and
      parameterized a new nonbonded model for metal ions by adding a 1/r4 term to the
      12-6 model. We call it the 12-6-4 LJ-type nonbonded model due to its mathematical
      construction. Parameters were determined for 16 +2 metal ions for the TIP3P,
      SPC/E and TIP4PEW water models. The final parameters reproduce the experimental
      hydration free energies (HFE), ion-oxygen distances (IOD) in the first solvation
      shell and coordination numbers (CN) accurately for the metal ions investigated.
      Preliminary tests on MgCl2 at different concentrations in aqueous solution and
      Mg2+--nucleic acid systems show reasonable results suggesting that the present
      parameters can work in mixed systems. The 12-6-4 LJ-type nonbonded model is
      readily adopted into standard force fields like AMBER, CHARMM and OPLS-AA with
      only a modest computational overhead. The new nonbonded model doesn't consider
      charge-transfer effects explicitly and, hence, may not suitable for the
      simulation of systems where charge-transfer effects play a decisive role.

PMID- 24659927
TI  - An Anisotropic Coarse-Grained Model for Proteins Based On Gay-Berne and Electric
      Multipole Potentials.
AB  - Gay-Berne anisotropic potential has been widely used to evaluate the non-bonded
      interactions between coarse-grained particles being described as elliptical rigid
      bodies. In this paper, we are presenting a coarse-grained model for twenty kinds
      of amino acids and proteins, based on the anisotropic Gay-Berne and point
      electric multipole (EMP) potentials. We demonstrate that the anisotropic coarse
      grained model, namely GBEMP model, is able to reproduce many key features
      observed from experimental protein structures (Dunbrack Library) as well as from
      atomistic force field simulations (using AMOEBA, AMBER and CHARMM force fields)
      while saving the computational cost by a factor of about 10~200 depending on
      specific cases and atomistic models. More importantly, unlike other coarse
      grained approaches, our framework is based on the fundamental intermolecular
      forces with explicit treatment of electrostatic and repulsion-dispersion forces.
      As a result, the coarse-grained protein model presented an accurate description
      of non-bonded interactions (particularly electrostatic component) between hetero
      /homo-dimers (such as peptide-peptide, peptide-water). In addition, the
      encouraging performance of the model was reflected by the excellent correlation
      between GBEMP and AMOEBA models in the calculations of the dipole moment of
      peptides. In brief, the GBEMP model given here is general and transferable,
      suitable for simulating complex biomolecular systems.

PMID- 24659928
TI  - Sexuality-related work discrimination and its association with the health of
      sexual minority emerging and young adult men in the Detroit Metro Area.
AB  - Discrimination has been linked to negative health outcomes among minority
      populations. The increasing evidence regarding health disparities among sexual
      minorities has underscored the importance of addressing sexuality discrimination
      as a public health issue. We conducted a web-based survey between May and
      September of 2012 in order to obtain a diverse sample of young men who have sex
      with men (ages 18-29; N = 397; 83% gay; 49% Black, 27% White, 15% Latino) living
      in the Detroit Metro Area (Michigan, USA). Using multivariate regression models,
      we examined the association between overall health (self-rated health, days in
      prior month when their physical or mental health was not good, limited
      functionality) and experiences of sexuality-based work discrimination. Fifteen
      percent reported at least one experience of sexuality-based work discrimination
      in the prior year. Recent workplace discrimination was associated with poorer
      self-rated health, a greater number of days when health was not good, and more
      functional limitation. We discuss the importance of addressing sexuality-related
      discrimination as a public health problem and propose multilevel intervention
      strategies to address these discriminatory practices.

PMID- 24659929
TI  - Men who have sex with men's attitudes toward using color-coded wristbands to
      facilitate sexual communication at sex parties.
AB  - Sex parties are environments where men who have sex with men (MSM) have the
      opportunity to have sex with multiple partners over a brief period of time. Dim
      lighting and non-verbal communication are characteristics of sex parties that
      make sexual communication more challenging. We report on qualitative data from 47
      MSM who attended sex parties in New York City. Participants responded to distinct
      hypothetical scenarios involving the use of color-coded wristbands to communicate
      (1) condom use preferences, (2) sexual position (e.g., top, bottom) and (3) HIV
      status at sex parties. The majority had positive-to-neutral attitudes toward
      color-coded wristbands to indicate (1) condom use preference and (2) sexual
      position (70.8%, 75.0% HIV-positive; 63.6%, 81.8%, HIV-negative respectively).
      These men cited that wristbands would facilitate the process of pursuing partners
      with similar interests while also avoiding the discomforts of verbal
      communication. In contrast, 41.7% of HIV-positive and 50.0% of HIV-negative men
      expressed unfavorable attitudes to using wristbands to communicate HIV status.
      These men cited the potential for HIV-status discrimination as well as suspicions
      around dishonest disclosure. Although participants were receptive to utilizing
      color-coded wristbands at sex parties to convey certain information, it may be
      unfeasible to use wristbands to communicate HIV status.

PMID- 24659930
TI  - Lifestyle Modifications and Colorectal Cancer.
AB  - Many studies suggest that Western lifestyle and dietary factors may be
      responsible for the high incidence of colorectal cancer in industrialized
      countries. Consumption of high amounts of red and processed meat and low intake
      of fiber and multiple protective phytochemicals found in fruits, vegetables, and
      whole grains might be responsible for the high incidence of this neoplasm in the
      Western world. Additionally, obesity, lack of physical activity, tobacco and
      alcohol use, sleep deprivation, and other factors have been proven to further
      increase the risk of colorectal cancer. Identifying and understanding the
      mechanisms through which they impact colon carcinogenesis is needed for the
      introduction of protective lifestyle recommendations.

PMID- 24659931
TI  - Dose calculations for [(131)i] meta-iodobenzylguanidine-induced bystander
      effects.
AB  - Targeted radiotherapy is a potentially useful treatment for some cancers and may
      be potentiated by bystander effects. However, without estimation of absorbed
      dose, it is difficult to compare the effects with conventional external radiation
      treatment. METHODS: Using the Vynckier - Wambersie dose point kernel, a model for
      dose rate evaluation was created allowing for calculation of absorbed dose values
      to two cell lines transfected with the noradrenaline transporter (NAT) gene and
      treated with [(131)I]MIBG. RESULTS: The mean doses required to decrease surviving
      fractions of UVW/NAT and EJ138/NAT cells, which received medium from [(131)I]MIBG
      treated cells, to 25 - 30% were 1.6 and 1.7 Gy respectively. The maximum mean
      dose rates achieved during [(131)I]MIBG treatment were 0.09 - 0.75 Gy/h for
      UVW/NAT and 0.07 - 0.78 Gy/h for EJ138/NAT. These were significantly lower than
      the external beam gamma radiation dose rate of 15 Gy/h. In the case of control
      lines which were incapable of [(131)I]MIBG uptake the mean absorbed doses
      following radiopharmaceutical were 0.03 - 0.23 Gy for UVW and 0.03 - 0.32 Gy for
      EJ138. CONCLUSION: [(131)I]MIBG treatment for ICCM production elicited a
      bystander dose-response profile similar to that generated by external beam gamma
      irradiation but with significantly greater cell death.

PMID- 24659933
TI  - Resveratrol attenuates exercise-induced adaptive responses in rats selectively
      bred for low running performance.
AB  - Low capacity runner (LCR) rats have been developed by divergent artificial
      selection for treadmill endurance capacity to explore an aerobic biology-disease
      connection. The beneficial effects of resveratrol supplementation have been
      demonstrated in endurance running. In this study it was examined whether 12 weeks
      of treadmill exercise training and/or resveratrol can retrieve the low running
      performance of the LCR and impact mitochondrial biogenesis and quality control.
      Resveratrol regressed running performance in trained LCR (p<0.05). Surprisingly,
      exercise and resveratrol treatments significantly decreased pAMPK/AMPK, SIRT1,
      SIRT4, forkhead transcription factor 1 (FOXO1) and mitochondrial transcription
      factor A (TFAM) levels in these animals (p<0.05). Mitochondrial fusion protein,
      HSP78 and polynucleotide phosphorylase were significantly induced in LCR-trained,
      LCR-resveratrol treated, LCR-trained and resveratol treated groups compared to
      LCR-controls. The data indicate that the AMPK-SIRT1-NAMPT-FOXO1 axis could be
      important to the limited aerobic endurance capacity of low running capacity rats.
      Resveratrol supplementation was not beneficial in terms of aerobic endurance
      performance, mitochondrial biogenesis, or quality control. 

PMID- 24659934
TI  - Transmission of signals from rats receiving high doses of microbeam radiation to
      cage mates: an inter-mammal bystander effect.
AB  - Inter-animal signaling from irradiated to non-irradiated organisms has been
      demonstrated for whole body irradiated mice and also for fish. The aim of the
      current study was to look at radiotherapy style limited exposure to part of the
      body using doses relevant in preclinical therapy. High dose homogenous field
      irradiation and the use of irradiation in the microbeam radiation therapy mode at
      the European Synchrotron Radiation Facility (ESRF) at Grenoble was tested by
      giving high doses to the right brain hemisphere of the rat. The right and left
      cerebral hemispheres and the urinary bladder were later removed to determine
      whether abscopal effects could be produced in the animals and also whether
      effects occurred in cage mates housed with them. The results show strong
      bystander signal production in the contra-lateral brain hemisphere and weaker
      effects in the distant bladder of the irradiated rats. Signal strength was
      similar or greater in each tissue in the cage mates housed for 48hrs with the
      irradiated rats. Our results support the hypothesis that proximity to an
      irradiated animal induces signalling changes in an unirradiated partner. If
      similar signaling occurs between humans, the results could have implications for
      caregivers and hospital staff treating radiotherapy patients. 

PMID- 24659935
TI  - Concentration-Dependent Effects of Rhodiola Rosea on Long-Term Survival and
      Stress Resistance of Yeast Saccharomyces Cerevisiae: The Involvement of YAP 1 and
      MSN2/4 Regulatory Proteins.
AB  - Concentration-dependent effects of aqueous extract from R. rosea root on long
      term survival and stress resistance of budding yeast Saccharomyces cerevisiae
      were studied. At low concentrations, R. rosea aqueous extract extended yeast
      chronological lifespan, enhanced oxidative stress resistance of stationary-phase
      cells and resistance to number stressors in exponentially growing cultures. At
      high concentrations, R. rosea extract sensitized yeast cells to stresses and
      shortened yeast lifespan. These biphasic concentration-responses describe a
      common hormetic phenomenon characterized by a low-dose stimulation and a high
      dose inhibition. Yeast pretreatment with low doses of R. rosea extract enhanced
      yeast survival and prevented protein oxidation under H2O2-induced oxidative
      stress. Positive effect of R. rosea extract on yeast survival under heat shock
      exposure was not accompanied with changes in antioxidant enzyme activities and
      levels of oxidized proteins. The deficiency in transcriptional regulators,
      Msn2/Msn4 and Yap1, abolished the positive effect of low doses of R. rosea
      extract on yeast viability under stress challenges. Potential involvement of
      Msn2/Msn4 and Yap1 regulatory proteins in realization of R. rosea beneficial
      effects is discussed. 

PMID- 24659932
TI  - Adaptation and sensitization to proteotoxic stress.
AB  - Although severe stress can elicit toxicity, mild stress often elicits
      adaptations. Here we review the literature on stress-induced adaptations versus
      stress sensitization in models of neurodegenerative diseases. We also describe
      our recent findings that chronic proteotoxic stress can elicit adaptations if the
      dose is low but that high-dose proteotoxic stress sensitizes cells to subsequent
      challenges. In these experiments, long-term, low-dose proteasome inhibition
      elicited protection in a superoxide dismutase-dependent manner. In contrast,
      acute, high-dose proteotoxic stress sensitized cells to subsequent proteotoxic
      challenges by eliciting catastrophic loss of glutathione. However, even in the
      latter model of synergistic toxicity, several defensive proteins were upregulated
      by severe proteotoxicity. This led us to wonder whether high-dose proteotoxic
      stress can elicit protection against subsequent challenges in astrocytes, a cell
      type well known for their resilience. In support of this new hypothesis, we found
      that the astrocytes that survived severe proteotoxicity became harder to kill.
      The adaptive mechanism was glutathione dependent. If these findings can be
      generalized to the human brain, similar endogenous adaptations may help explain
      why neurodegenerative diseases are so delayed in appearance and so slow to
      progress. In contrast, sensitization to severe stress may explain why defenses
      eventually collapse in vulnerable neurons. 

PMID- 24659936
TI  - Simultaneous analysis of p53 protein expression and cell proliferation in
      irradiated human lymphocytes by flow cytometry.
AB  - P53 protein has an intrinsic role in modulating the cellular response against DNA
      radioinduced damages and has been pointed out as an indirect indicator of
      individual radiosensitivity. The rate of cell proliferation is also a parameter
      that has been related to tissue sensitivity to radiation. However, this feature
      is yet understudied. In this context, the aim of this work was to employ Flow
      Cytometry (FC) for simultaneously assessing of p53 protein expression levels
      together with cellular proliferation rate of irradiated human lymphocytes. From
      in vitro irradiated human blood samples, mononuclear cells were isolated and
      labeled with Carboxylfluorescein Diacetate Succinimidyl Ester (CFSE) prior to
      phytohaemagglutinin (PHA) stimulation in culture for 96 hours. Cells were also
      labeled with anti-p53 monoclonal antibody PE-conjugated in order to analyze
      either proliferation rate or p53 expression levels by FC. It was verified a
      reduction in the proliferation rate of irradiated lymphocytes and, in parallel, a
      rise in the p53 expression levels, similar for quiescent and proliferating
      lymphocytes. The results emphasize the importance of the use of CFSE-stained
      lymphocytes in assays associated to proliferation rate and the use of this
      methodology in several studies, such as for evaluating individual
      radiosensitivity. 

PMID- 24659937
TI  - Hormesis and paradoxical effects of wheat seedling (triticum aestivum L.)
      parameters upon exposure to different pollutants in a wide range of doses.
AB  - Chlorophyll and carotenoid content (ChCar), lipid peroxidation (LP) and growth
      parameters (GP) in plants are often used for environmental pollution estimation.
      However, the nonmonotonic dose-response dependences (hormesis and paradoxical
      effects) of these indices are insufficiently explored following exposure to
      different pollutants. In this experiment, we studied nonmonotonic changes in
      ChCar, LP, GP in wheat seedlings (Triticum aestivum L.) upon exposure to lead,
      cadmium, copper, manganese, formaldehyde, the herbicide glyphosate, and sodium
      chloride in a wide range from sublethal concentration to 10(2)-10(5) times lower
      concentrations. 85.7% of dose-response dependences were nonmonotonic (of these,
      5.5% were hormesis and paradoxical effects comprised 94.5%). Multiphasic
      dependences were the most widespread type of paradoxical effect. Hormesis was a
      part of some multiphasic responses (i.e. paradoxical effects), which indicates a
      relationship between these phenomena. Sublethal pollutant concentrations
      significantly increased LP (to 2.0-2.4 times, except for manganese and
      glyphosate) and decreased GP (to 2.1-36.6 times, except for glyphosate), while
      ChCar was reduced insignificantly, normalized or even increased. Lower pollutant
      concentrations caused a moderate deviation in all parameters from the control
      (not more than 62%) for hormesis and paradoxical effects. The seedling parameters
      could have different types of nonmonotonic responses upon exposure to the same
      pollutant. 

PMID- 24659938
TI  - Synthetic triterpenoids can protect against toxicity without reducing the
      efficacy of treatment with Carboplatin and Paclitaxel in experimental lung
      cancer.
AB  - Synthetic oleanane triterpenoids are multifunctional drugs being developed for
      the prevention and treatment of a variety of chronic diseases driven by
      inflammation and oxidative stress. Low nanomolar concentrations of triterpenoids
      inhibit the induction of inflammatory cytokines, and these drugs are potent
      activators of the Nrf2 cytoprotective pathway. In contrast, low micromolar
      concentrations of triterpenoids increased the production of ROS and induced
      apoptosis in a dose-dependent manner in malignant MCF10 CA1a breast cancer cells.
      Because cancer cells respond differently to ROS than normal cells, it should be
      possible to exploit these differences therapeutically. In an experimental model
      of lung cancer, the triterpenoids activated the Nrf2 pathway, as seen by
      induction of the cytoprotective enzyme NQO1, and reduced the toxicity of
      carboplatin and paclitaxel. The induction of the Nrf2 pathway in the lung did not
      suppress the efficacy of treatment with carboplatin and paclitaxel, as the
      average tumor burden in the group treated with the combination of CDDO-Me and
      carboplatin/paclitaxel decreased by 90% (P < 0.05 vs. the controls and both
      single treatment groups). Understanding the dose response of triterpenoids and
      related drugs will help provide the proper context for optimizing their potential
      clinical utility. 

PMID- 24659939
TI  - Induction of MRSA Biofilm by Low-Dose beta-Lactam Antibiotics: Specificity,
      Prevalence and Dose-Response Effects.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital
      and community-associated infections. The formation of adherent clusters of cells
      known as biofilms is an important virulence factor in MRSA pathogenesis. Previous
      studies showed that subminimal inhibitory (sub-MIC) concentrations of methicillin
      induce biofilm formation in the community-associated MRSA strain LAC. In this
      study we measured the ability sub-MIC concentrations of eight other beta-lactam
      antibiotics and six non-beta-lactam antibiotics to induce LAC biofilm. All eight
      beta-lactam antibiotics, but none of the non-beta-lactam antibiotics, induced LAC
      biofilm. The dose-response effects of the eight beta-lactam antibiotics on LAC
      biofilm varied from biphasic and bimodal to near-linear. We also found that sub
      MIC methicillin induced biofilm in 33 out of 39 additional MRSA clinical
      isolates, which also exhibited biphasic, bimodal and linear dose-response curves.
      The amount of biofilm formation induced by sub-MIC methicillin was inversely
      proportional to the susceptibility of each strain to methicillin. Our results
      demonstrate that induction of biofilm by sub-MIC antibiotics is a common
      phenotype among MRSA clinical strains and is specific for beta-lactam
      antibiotics. These findings may have relevance to the use of beta-lactam
      antibiotics in clinical and agricultural settings. 

PMID- 24659940
TI  - On the radiation-leukemia dose-response relationship among recovery workers after
      the chernobyl accident.

PMID- 24659941
TI  - Rhodium-Catalyzed Asymmetric 1,4-Additions, in Water at Room Temperature, with In
      Flask Catalyst Recycling.
AB  - Using the newly introduced designer surfactant polyethyleneglycol ubiquinol
      sebacate (PQS), as the platform for micellar catalysis, nonracemic BINAP has been
      covalently attached and rhodium(I) inserted to form PQS-BINAP-Rh. This species,
      the first example of a nonracemically-ligated transition metal catalyst-tethered
      amphiphile, can be utilized for Rh-catalyzed asymmetric conjugate addition
      reactions of arylboronic acids to acyclic and cyclic enones. These are performed
      in water at room temperature, while the catalyst can be recycled without its
      removal from water in the reaction vessel.

PMID- 24659942
TI  - Hepatitis e: the 'new kid on the block' or an old friend?

PMID- 24659943
TI  - Emerging Pathogens - How Safe is Blood?
AB  - During the last few decades, blood safety efforts were mainly focused on
      preventing viral infections. However, humanity's increased mobility and improved
      migration pathways necessitate a global perspective regarding other transfusion
      transmitted pathogens. This review focuses on the general infection risk of blood
      components for malaria, dengue virus, Trypanosoma cruzi (Chagas disease) and
      Babesia spp. Approximately 250 million people become infected by Plasmodium spp.
      per year. Dengue virus affects more than 50 million people annually in more than
      100 countries; clinically, it can cause serious diseases, such as dengue
      haemorrhagic fever and dengue shock syndrome. Chagas disease, which is caused by
      Trypanosoma cruzi, mainly occurs in South America and infects approximately 10
      million people annually. Babesia spp. is a parasitic infection that infects red
      blood cells; although many infections are asymptomatic, severe clinical disease
      has been reported, especially in the elderly. Screening assays are available for
      all considered pathogens but make screening strategies more complex and more
      expensive. A general pathogen inactivation for all blood components (whole blood)
      promises to be a long-term, sustainable solution for both known and unknown
      pathogens. Transfusion medicine therefore eagerly awaits such a system. 

PMID- 24659944
TI  - Diagnostic methods for platelet bacteria screening: current status and
      developments.
AB  - Bacterial contamination of blood components and the prevention of transfusion
      associated bacterial infection still remains a major challenge in transfusion
      medicine. Over the past few decades, a significant reduction in the transmission
      of viral infections has been achieved due to the introduction of mandatory virus
      screening. Platelet concentrates (PCs) represent one of the highest risks for
      bacterial infection. This is due to the required storage conditions for PCs in
      gas-permeable containers at room temperature with constant agitation, which
      support bacterial proliferation from low contamination levels to high titers. In
      contrast to virus screening, since 1997 in Germany bacterial testing of PCs is
      only performed as a routine quality control or, since 2008, to prolong the shelf
      life to 5 days. In general, bacterial screening of PCs by cultivation methods is
      implemented by the various blood services. Although these culturing systems will
      remain the gold standard, the significance of rapid methods for screening for
      bacterial contamination has increased over the last few years. These new methods
      provide powerful tools for increasing the bacterial safety of blood components.
      This article summarizes the course of policies and provisions introduced to
      increase bacterial safety of blood components in Germany. Furthermore, we give an
      overview of the different diagnostic methods for bacterial screening of PCs and
      their current applicability in routine screening processes. 

PMID- 24659945
TI  - Autochthonous hepatitis e virus infections: a new transfusion-associated risk?
AB  - Hepatitis E virus (HEV) has been recognized since 2004 as a transfusion
      transmissible infectious agent, and recent epidemiological data suggest that it
      may pose a safety threat to the blood supply. It has recently become obvious that
      hepatitis E is endemic in industrialized countries, and that more infections are
      autochthonous than travel-associated. Epidemiological and phylogenetic analysis
      suggests that HEV infection has to be considered as a zoonosis and that viral
      transmission from animals (pigs, wild animals) occurs through food or direct
      contact. The seroprevalence and incidence of HEV in the general population and
      blood donors in European countries indicate an underestimated risk for
      transfusion transmissions. Recently reported cases of transfusion transmission of
      HEV infection, and detection of viremic, asymptomatic blood donors in nucleic
      acid amplification technique screening programs give an indication of the
      importance of this virus. Diagnostic assays for detection of anti-HEV antibodies,
      HEV antigens and RNA are discussed. Recent studies support the idea that active
      immunization can prevent hepatitis E, highlighting the need for vaccination
      programs. Here we review current knowledge of HEV and its epidemiology, blood
      transmission and prevention of this disease with emphasis on blood supply. 

PMID- 24659946
TI  - Prevention of Transfusion-Transmitted Cytomegalovirus Infections: Which is the
      Optimal Strategy?
AB  - Traditionally, leukoreduction and selection of blood products from seronegative
      donors have been used as alternative strategies to reduce the risk of transfusion
      transmitted cytomegalovirus infections (TT-CMV) in atrisk patients. After the
      introduction of universal leukoreduction for red blood cell and platelet
      concentrates in Germany, a controversy evolved as to whether the additional
      selection of blood products from seronegative donors would reduce or even
      increase the risk of TT-CMV. This review summarizes the current knowledge about
      CMV infections in blood donors and the implications of this information on the
      effect of potential transfusion strategies. Even though there are conflicting
      data about the incidence of TT-CMV remaining after the introduction of
      leukodepletion, it has been clearly shown that both prevalence and concentration
      of CMV DNA in peripheral blood are highest in newly seropositive donors.
      Therefore, avoidance of blood products from these donors is the most important
      goal of any transfusion strategy. This goal can be reached by: i) selection of
      blood products from seronegative donors, ii) provision of CMV DNA-negative blood
      products, or iii) provision of blood from long-term seropositive donors. In cases
      of suspected TT-CMV, all implicated donors should be investigated carefully to
      gather further knowledge on which donors confer the lowest risk for TT-CMV. 

PMID- 24659947
TI  - Risk Minimization Measures for Blood Screening HIV-1 Nucleic Acid Amplification
      Technique Assays in Germany.
AB  - BACKGROUND: Several publications describe HIV-1 RNA false-negative results or
      viral load underquantitation associated with Communaute Europeenne(CE)-marked
      qualitative or quantitative nucleic acid amplification technique (NAT) assays. 6
      cases occurred during blood screening in Germany, with 2 of them causing HIV-1
      transmissions to recipients of blood components. The implicated NAT assays were
      mono-target assays amplifying in different viral genome regions (gag or long
      terminal repeat). METHODS: Specimens characterized by HIV-1 NAT underquantitation
      or false-negative NAT results were comparatively investigated in CE-marked HIV-1
      NAT systems of different design to identify potential reasons. The target regions
      of the viral nucleic acids were sequenced and these sequences compared to primers
      and probes of the assays. Potential risk minimization measures were considered
      for quantitative and blood-screening HIV-1 NAT systems. RESULTS: Nucleotide
      sequencing of the viral target region in cases of HIV-1 RNA underquantitation or
      false-negative test results revealed new HIV-1 variants that were mismatched with
      primers and probes used in some mono-target assays. So far, dualtarget NAT assays
      have not been associated with mismatch-based false-negative test results. From
      2015, the Paul Ehrlich Institute will request HIV-1 NAT assays of dual-target
      design or an analogous solution for further reducing the risk in blood screening.
      CONCLUSION: HIV differs from other blood-borne viruses with regard to its fast
      evolution of new viral variants. The evolution of new sequences is hardly
      predictable; therefore, NAT assays with only 1 target region appear to be more
      vulnerable to sequence variations than dual-target assays. The associated risk
      may be higher for HIV-1 NAT assays used for blood screening compared to
      quantitative assays used for monitoring HIV-1-infected patients. In HIV-1
      screening NAT assays of dual-target design may adequately address the risk
      imposed by new HIV-1 variants.

PMID- 24659948
TI  - Parvovirus b19 infections and blood counts in blood donors.
AB  - OBJECTIVES: Parvovirus B19 (B19V) is a transfusion-transmissible virus. To obtain
      data about the prevalence, incidence, the course of B19V infection in blood
      donors and whether B19V might impair their blood counts, samples from blood
      donors with B19V infection were investigated. METHODS: Blood donations were
      screened for B19V DNA using the Cobas TaqScreen DPX Test(r) in mini-pools. B19V
      DNA concentration, anti-B19V IgG antibody titer and blood counts were determined
      in positive donors. RESULTS: 157/23,889 (0.66%) donors provided 347 B19V DNA
      positive samples. Prevalence of B19V infection was 0.45%, incidence 0.20%. B19V
      DNA concentrations were predominantly low; only in 8 samples were viral loads of
      >=10(5) IU B19V DNA/ml plasma detectable. Besides a slight decrease in
      hemoglobin, hematocrit, mean corpuscular volume, mean cellular hemoglobin and
      mean hemoglobin concentration, no major differences in blood counts occurred in
      B19V DNA-positive samples. In samples with a low B19V DNA concentration, anti
      B19V IgG titers were rather high. 98 donors provided at least 1 B19V DNA-positive
      follow-up sample, indicating a prolonged viremia. CONCLUSIONS: B19V infection
      induced no major impairment in the blood counts. In donors with low-level
      viremia, infectivity through their donations is probably reduced by high antibody
      titers. Low-level viremia is prolonged, probably exceeding 1 year in many cases.

PMID- 24659951
TI  - A single-tube real-time PCR assay for Mycoplasma detection as a routine quality
      control of cell therapeutics.
AB  - BACKGROUND: Contamination of cell culture and biological material by mollicute
      species is an important safety issue and requires testing. We have developed a
      singletube real-time polymerase chain reaction (PCR) assay for rapid detection of
      Mollicutes species stipulated by the European Pharmacopeia. METHODS: Primers and
      TaqMan probes (FAM-labeled) were deduced from 16S rDNA sequence alignment of 18
      mollicutes species. A synthetic internal control (IC) DNA and an IC-specific
      TaqMan probe (VIC-labeled) were included. The analytical sensitivity of the assay
      was determined on DNA dilutions from 12 mollicute strains. Specificity was proven
      by the use of DNA from other bacteria. RESULTS: Analytical sensitivities of the
      PCR assay were in the range of 405-2,431 genomes/ml for 11 of the 12 tested
      mollicute DNA samples. The lowest sensitivity was found for Ureaplasma
      urealyticum (19,239 genomes/ml). Negative results for DNA samples from 3
      different ubiquitous bacteria demonstrated the specificity of the PCR assay for
      Mollicutes. Direct testing of cell culture supernatants spiked with Mycoplasma
      orale revealed similar sensitivity compared to isolated DNA. CONCLUSIONS: Our
      single-tube real-time PCR assay with internal reaction control enables rapid and
      specific detection of mollicute contaminants. The test protocol is suitable for
      routine quality control of cell therapeutics.

PMID- 24659950
TI  - Usutu virus.

PMID- 24659949
TI  - Coxiella burnetii - Pathogenic Agent of Q (Query) Fever.

PMID- 24659952
TI  - BOLD fMRI signal characteristics of S1- and S2-SSFP at 7 Tesla.
AB  - OBJECT: To compare the BOLD fMRI signal characteristics at in the cortex and on
      the pial surface for a non-balanced steady-state free precession sequence (nb
      SSFP) at 7 T. MATERIALS AND METHODS: A multi-echo nb-SSFP sequence was used for
      high resolution fMRI at 7 T. Two S1 (S(+)) echoes at different echo times were
      acquired together with an S2 (S(-)) echo. The primary visual cortex (V1) was
      examined using a reversing checkerboard paradigm at an isotropic resolution of
      0.75 mm, with 35 volumes acquired and a total scan time of 27 min. RESULTS:
      Significant activation was observed in all subjects for all three acquired
      echoes. For the S1 signal at the longer TE, the activation induced signal change
      was about 4% in the cortex and 10% at the cortical surface, while for S2 the
      corresponding values were 3 and 5%. CONCLUSION: For both S1 and S2 data, the BOLD
      signal peaks at the pial surface. The large pial surface signal change in S2 may
      be caused by dynamic averaging around post-capillary vessels embedded within CSF.
      This is made possible by the long diffusion times of the pathways contributing to
      the S2 signal and the relatively high diffusion coefficient of CSF. The results
      indicate that S2-SSFP might not be a suited alternative to spin-echo for high
      resolution fMRI at 7 T.

PMID- 24659954
TI  - Imaging and monitoring astrocytes in health and disease.

PMID- 24659955
TI  - Persistent barrage firing in cortical interneurons can be induced in vivo and may
      be important for the suppression of epileptiform activity.
AB  - Neural circuits are typically maintained in a state of dynamic equilibrium by
      balanced synaptic excitation and inhibition. However, brain regions that are
      particularly susceptible to epilepsy may have evolved additional specialized
      mechanisms for inhibiting over-excitation. Here we identify one such possible
      mechanism in the cerebral cortex and hippocampus of mice. Recently it was
      reported that some types of GABAergic interneurons can slowly integrate
      excitatory inputs until eventually they fire persistently in the absence of the
      original stimulus. This property, called persistent firing or retroaxonal barrage
      firing (BF), is of unknown physiological importance. We show that two common
      types of interneurons in cortical regions, neurogliaform (NG) cells and fast
      spiking (FS) cells, are unique in exhibiting BF in acute slices (~85 and ~23%
      success rate for induction, respectively). BF can also be induced in vivo,
      although the success rate for induction is lower (~60% in NG cells). In slices,
      BF could reliably be triggered by trains of excitatory synaptic input, as well as
      by exposure to proconvulsant bath solutions (elevated extracellular K(+),
      blockade of GABAA receptors). Using pair recordings in slices, we confirmed that
      barrage-firing NG cells can produce synaptic inhibition of nearby pyramidal
      neurons, and that this inhibition outlasts the original excitation. The ubiquity
      of NG and FS cells, together with their ability to fire persistently following
      excessive excitation, suggests that these interneurons may function as cortical
      sentinels, imposing an activity-dependent brake on undesirable neuronal
      hyperexcitability. 

PMID- 24659956
TI  - Color opponent receptive fields self-organize in a biophysical model of visual
      cortex via spike-timing dependent plasticity.
AB  - Although many computational models have been proposed to explain orientation maps
      in primary visual cortex (V1), it is not yet known how similar clusters of color
      selective neurons in macaque V1/V2 are connected and develop. In this work, we
      address the problem of understanding the cortical processing of color information
      with a possible mechanism of the development of the patchy distribution of color
      selectivity via computational modeling. Each color input is decomposed into a
      red, green, and blue representation and transmitted to the visual cortex via a
      simulated optic nerve in a luminance channel and red-green and blue-yellow
      opponent color channels. Our model of the early visual system consists of
      multiple topographically-arranged layers of excitatory and inhibitory neurons,
      with sparse intra-layer connectivity and feed-forward connectivity between
      layers. Layers are arranged based on anatomy of early visual pathways, and
      include a retina, lateral geniculate nucleus, and layered neocortex. Each neuron
      in the V1 output layer makes synaptic connections to neighboring neurons and
      receives the three types of signals in the different channels from the
      corresponding photoreceptor position. Synaptic weights are randomized and learned
      using spike-timing-dependent plasticity (STDP). After training with natural
      images, the neurons display heightened sensitivity to specific colors.
      Information-theoretic analysis reveals mutual information between particular
      stimuli and responses, and that the information reaches a maximum with fewer
      neurons in the higher layers, indicating that estimations of the input colors can
      be done using the output of fewer cells in the later stages of cortical
      processing. In addition, cells with similar color receptive fields form clusters.
      Analysis of spiking activity reveals increased firing synchrony between neurons
      when particular color inputs are presented or removed (ON-cell/OFF-cell). 

PMID- 24659957
TI  - Increased intelligence is a myth (so far).

PMID- 24659953
TI  - Glial response during cuprizone-induced de- and remyelination in the CNS: lessons
      learned.
AB  - Although astrogliosis and microglia activation are characteristic features of
      multiple sclerosis (MS) and other central nervous system (CNS) lesions the exact
      functions of these events are not fully understood. Animal models help to
      understand the complex interplay between the different cell types of the CNS and
      uncover general mechanisms of damage and repair of myelin sheaths. The so called
      cuprizone model is a toxic model of demyelination in the CNS white and gray
      matter, which lacks an autoimmune component. Cuprizone induces apoptosis of
      mature oligodendrocytes that leads to a robust demyelination and profound
      activation of both astrocytes and microglia with regional heterogeneity between
      different white and gray matter regions. Although not suitable to study
      autoimmune mediated demyelination, this model is extremely helpful to elucidate
      basic cellular and molecular mechanisms during de- and particularly remyelination
      independently of interactions with peripheral immune cells. Phagocytosis and
      removal of damaged myelin seems to be one of the major roles of microglia in this
      model and it is well known that removal of myelin debris is a prerequisite of
      successful remyelination. Furthermore, microglia provide several signals that
      support remyelination. The role of astrocytes during de- and remyelination is not
      well defined. Both supportive and destructive functions have been suggested.
      Using the cuprizone model we could demonstrate that there is an important
      crosstalk between astrocytes and microglia. In this review we focus on the role
      of glial reactions and interaction in the cuprizone model. Advantages and
      limitations of as well as its potential therapeutic relevance for the human
      disease MS are critically discussed in comparison to other animal models. 

PMID- 24659958
TI  - Beyond the borders: the gates and fences of neuroimmune interaction.

PMID- 24659961
TI  - Object location and object recognition memory impairments, motivation deficits
      and depression in a model of Gulf War illness.
AB  - Memory and mood deficits are the enduring brain-related symptoms in Gulf War
      illness (GWI). Both animal model and epidemiological investigations have
      indicated that these impairments in a majority of GW veterans are linked to
      exposures to chemicals such as pyridostigmine bromide (PB, an antinerve gas
      drug), permethrin (PM, an insecticide) and DEET (a mosquito repellant)
      encountered during the Persian Gulf War-1. Our previous study in a rat model has
      shown that combined exposures to low doses of GWI-related (GWIR) chemicals PB,
      PM, and DEET with or without 5-min of restraint stress (a mild stress paradigm)
      causes hippocampus-dependent spatial memory dysfunction in a water maze test
      (WMT) and increased depressive-like behavior in a forced swim test (FST). In this
      study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we
      investigated whether the memory deficiency identified earlier in a WMT is
      reproducible with an alternative and stress free hippocampus-dependent memory
      test such as the object location test (OLT). We also ascertained the possible co
      existence of hippocampus-independent memory dysfunction using a novel object
      recognition test (NORT), and alterations in mood function with additional tests
      for motivation and depression. Our results provide new evidence that exposure to
      low doses of GWIR-chemicals and mild stress for 4 weeks causes deficits in
      hippocampus-dependent object location memory and perirhinal cortex-dependent
      novel object recognition memory. An open field test performed prior to other
      behavioral analyses revealed that memory impairments were not associated with
      increased anxiety or deficits in general motor ability. However, behavioral tests
      for mood function such as a voluntary physical exercise paradigm and a novelty
      suppressed feeding test (NSFT) demonstrated decreased motivation levels and
      depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus
      dependent and hippocampus-independent memory impairments as well as mood
      dysfunction in a rat model. 

PMID- 24659959
TI  - MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and
      Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat
      Model of Psychosis.
AB  - Flexible behavior in dynamic, real-world environments requires more than static
      spatial learning and memory. Discordant and unstable cues must be organized in
      coherent subsets to give rise to meaningful spatial representations. We model
      this form of cognitive coordination on a rotating arena - Carousel where arena-
      and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble
      activity can repeatedly switch between multiple representations of such an
      environment. Injection of tetrodotoxin into one hippocampus prevents cognitive
      coordination during avoidance of a stationary room-defined place on the Carousel
      and increases coactivity of previously unrelated neurons in the uninjected
      hippocampus. Place avoidance on the Carousel is impaired after systemic
      administration of non-competitive NMDAr blockers (MK-801) used to model
      schizophrenia in animals and people. We tested if this effect is due to cognitive
      disorganization or other effect of NMDAr antagonism such as hyperlocomotion,
      spatial memory impairment, or general learning deficit. We also examined if the
      same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in
      the hippocampus. IEG expression is triggered in neuronal nuclei in a context
      specific manner after behavioral exploration and it is used to map activity in
      neuronal populations. IEG expression is critical for maintenance of synaptic
      plasticity and memory consolidation. We show that the same dose of MK-801 that
      impairs spatial coordination of rats on the Carousel also eliminates contextual
      specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to
      increased similarity between ensembles activated in different environments,
      consistent with the idea that it is caused by increased coactivity between
      neurons, which did not previously fire together. Our data support the proposition
      of the Hypersynchrony theory that cognitive disorganization in psychosis is due
      to increased coactivity between unrelated neurons. 

PMID- 24659960
TI  - Does temporal discounting explain unhealthy behavior? A systematic review and
      reinforcement learning perspective.
AB  - The tendency to make unhealthy choices is hypothesized to be related to an
      individual's temporal discount rate, the theoretical rate at which they devalue
      delayed rewards. Furthermore, a particular form of temporal discounting,
      hyperbolic discounting, has been proposed to explain why unhealthy behavior can
      occur despite healthy intentions. We examine these two hypotheses in turn. We
      first systematically review studies which investigate whether discount rates can
      predict unhealthy behavior. These studies reveal that high discount rates for
      money (and in some instances food or drug rewards) are associated with several
      unhealthy behaviors and markers of health status, establishing discounting as a
      promising predictive measure. We secondly examine whether intention-incongruent
      unhealthy actions are consistent with hyperbolic discounting. We conclude that
      intention-incongruent actions are often triggered by environmental cues or
      changes in motivational state, whose effects are not parameterized by hyperbolic
      discounting. We propose a framework for understanding these state-based effects
      in terms of the interplay of two distinct reinforcement learning mechanisms: a
      "model-based" (or goal-directed) system and a "model-free" (or habitual) system.
      Under this framework, while discounting of delayed health may contribute to the
      initiation of unhealthy behavior, with repetition, many unhealthy behaviors
      become habitual; if health goals then change, habitual behavior can still arise
      in response to environmental cues. We propose that the burgeoning development of
      computational models of these processes will permit further identification of
      health decision-making phenotypes. 

PMID- 24659962
TI  - Who is going to walk? A review of the factors influencing walking recovery after
      spinal cord injury.
AB  - The recovery of walking function is considered of extreme relevance both by
      patients and physicians. Consequently, in the recent years, recovery of
      locomotion become a major objective of new pharmacological and rehabilitative
      interventions. In the last decade, several pharmacological treatment and
      rehabilitative approaches have been initiated to enhance locomotion capacity of
      SCI patients. Basic science advances in regeneration of the central nervous
      system hold promise of further neurological and functional recovery to be studied
      in clinical trials. Therefore, a precise knowledge of the natural course of
      walking recovery after SCI and of the factors affecting the prognosis for
      recovery has become mandatory. In the present work we reviewed the prognostic
      factors for walking recovery, with particular attention paid to the clinical ones
      (neurological examination at admission, age, etiology gender, time course of
      recovery). The prognostic value of some instrumental examinations has also been
      reviewed. Based on these factors we suggest that a reliable prognosis for walking
      recovery is possible. Instrumental examinations, in particular evoked potentials
      could be useful to improve the prognosis. 

PMID- 24659963
TI  - Potential Use of MEG to Understand Abnormalities in Auditory Function in Clinical
      Populations.
AB  - Magnetoencephalography (MEG) provides a direct, non-invasive view of neural
      activity with millisecond temporal precision. Recent developments in MEG analysis
      allow for improved source localization and mapping of connectivity between brain
      regions, expanding the possibilities for using MEG as a diagnostic tool. In this
      paper, we first describe inverse imaging methods (e.g., minimum-norm estimation)
      and functional connectivity measures, and how they can provide insights into
      cortical processing. We then offer a perspective on how these techniques could be
      used to understand and evaluate auditory pathologies that often manifest during
      development. Here we focus specifically on how MEG inverse imaging, by providing
      anatomically based interpretation of neural activity, may allow us to test which
      aspects of cortical processing play a role in (central) auditory processing
      disorder [(C)APD]. Appropriately combining auditory paradigms with MEG analysis
      could eventually prove useful for a hypothesis-driven understanding and diagnosis
      of (C)APD or other disorders, as well as the evaluation of the effectiveness of
      intervention strategies. 

PMID- 24659964
TI  - Decoding repetitive finger movements with brain activity acquired via non
      invasive electroencephalography.
AB  - We investigated how well repetitive finger tapping movements can be decoded from
      scalp electroencephalography (EEG) signals. A linear decoder with memory was used
      to infer continuous index finger angular velocities from the low-pass filtered
      fluctuations of the amplitude of a plurality of EEG signals distributed across
      the scalp. To evaluate the accuracy of the decoder, the Pearson's correlation
      coefficient (r) between the observed and predicted trajectories was calculated in
      a 10-fold cross-validation scheme. We also assessed attempts to decode finger
      kinematics from EEG data that was cleaned with independent component analysis
      (ICA), EEG data from peripheral sensors, and EEG data from rest periods. A
      genetic algorithm (GA) was used to select combinations of EEG channels that
      maximized decoding accuracies. Our results (lower quartile r = 0.18, median r =
      0.36, upper quartile r = 0.50) show that delta-band EEG signals contain useful
      information that can be used to infer finger kinematics. Further, the highest
      decoding accuracies were characterized by highly correlated delta band EEG
      activity mostly localized to the contralateral central areas of the scalp.
      Spectral analysis of EEG also showed bilateral alpha band (8-13 Hz) event related
      desynchronizations (ERDs) and contralateral beta band (20-30 Hz) event related
      synchronizations (ERSs) localized over central scalp areas. Overall, this study
      demonstrates the feasibility of decoding finger kinematics from scalp EEG
      signals. 

PMID- 24659965
TI  - Endoscopic surgery for traumatic acute subdural hematoma.
AB  - Traumatic acute subdural hematoma (ASDH) is generally addressed by craniotomy
      under general anesthesia. We report a patient whose traumatic ASDH was treated
      under local anesthesia by one-burr-hole endoscopic surgery. This 87-year-old
      woman had undergone coil embolization for a ruptured right middle-cerebral artery
      aneurysm and placement of a ventriculoperitoneal shunt for normal pressure
      hydrocephalus 5 years earlier. Upon admission, she manifested consciousness
      disturbance after suffering head trauma and right hemiplegia. Her Glasgow Coma
      Scale score was 8 (E2V2M4). Computed tomography (CT) demonstrated a thick, left
      frontotemporal ASDH. Due to her advanced age and poor condition, we performed
      endoscopic surgery rather than craniotomy to evacuate the ASDH. Under local
      anesthesia, we made a burr hole in her left forehead and increased its size to 15
      mm in diameter. After introducing a transparent sheath into the hematoma cavity
      with a rigid endoscope, the clot was evacuated with a suction tube. The arterial
      bleeding point was electrically coagulated. A postoperative CT scan confirmed the
      reduction of the hematoma. There was neither brain compression nor brain
      swelling. Her consciousness disturbance and right hemiplegia improved
      immediately. Endoscopic surgery may represent a viable method to address
      traumatic intracranial hematomas in some patients. 

PMID- 24659967
TI  - Integrated mechanisms of CaMKII-dependent ventricular remodeling.
AB  - CaMKII has been shown to be activated during different cardiac pathological
      processes, and CaMKII-dependent mechanisms contribute to pathological cardiac
      remodeling, cardiac arrhythmias, and contractile dysfunction during heart
      failure. Activation of CaMKII during cardiac stress results in a broad number of
      biological effects such as, on the one hand, acute effects due to phosphorylation
      of distinct cellular proteins as ion channels and calcium handling proteins and,
      on the other hand, integrative mechanisms by changing gene expression. This
      review focuses on transcriptional and epigenetic effects of CaMKII activation
      during chronic cardiac remodeling. Multiple mechanisms have been described how
      CaMKII mediates changes in cardiac gene expression. CaMKII has been shown to
      directly phosphorylate components of the cardiac gene regulation machinery.
      CaMKII phosphorylates several transcription factors such as CREB that induces the
      activation of specific gene programs. CaMKII activates transcriptional regulators
      also indirectly by phosphorylating histone deacetylases, especially HDAC4, which
      in turn inhibits transcription factors that drive cardiac hypertrophy, fibrosis,
      and dysfunction. Recent studies demonstrate that CaMKII also phosphorylate
      directly histones, which may contribute to changes in gene expression. These
      findings of CaMKII-dependent gene regulation during cardiac remodeling processes
      suggest novel strategies for CaMKII-dependent "transcriptional or epigenetic
      therapies" to control cardiac gene expression and function. Manipulation of
      CaMKII-dependent signaling pathways in the settings of pathological cardiac
      growth, remodeling, and heart failure represents an auspicious therapeutic
      approach. 

PMID- 24659968
TI  - Protein comparability assessments and potential applicability of high throughput
      biophysical methods and data visualization tools to compare physical stability
      profiles.
AB  - In this review, some of the challenges and opportunities encountered during
      protein comparability assessments are summarized with an emphasis on developing
      new analytical approaches to better monitor higher-order protein structures.
      Several case studies are presented using high throughput biophysical methods to
      collect protein physical stability data as function of temperature, agitation,
      ionic strength and/or solution pH. These large data sets were then used to
      construct empirical phase diagrams (EPDs), radar charts, and comparative
      signature diagrams (CSDs) for data visualization and structural comparisons
      between the different proteins. Protein samples with different sizes, post
      translational modifications, and inherent stability are presented: acidic
      fibroblast growth factor (FGF-1) mutants, different glycoforms of an IgG1 mAb
      prepared by deglycosylation, as well as comparisons of different formulations of
      an IgG1 mAb and granulocyte colony stimulating factor (GCSF). Using this
      approach, differences in structural integrity and conformational stability
      profiles were detected under stress conditions that could not be resolved by
      using the same techniques under ambient conditions (i.e., no stress). Thus, an
      evaluation of conformational stability differences may serve as an effective
      surrogate to monitor differences in higher-order structure between protein
      samples. These case studies are discussed in the context of potential utility in
      protein comparability studies. 

PMID- 24659966
TI  - Imaging of cerebrovascular pathology in animal models of Alzheimer's disease.
AB  - In Alzheimer's disease (AD), vascular pathology may interact with
      neurodegeneration and thus aggravate cognitive decline. As the relationship
      between these two processes is poorly understood, research has been increasingly
      focused on understanding the link between cerebrovascular alterations and AD.
      This has at last been spurred by the engineering of transgenic animals, which
      display pathological features of AD and develop cerebral amyloid angiopathy to
      various degrees. Transgenic models are versatile for investigating the role of
      amyloid deposition and vascular dysfunction, and for evaluating novel therapeutic
      concepts. In addition, research has benefited from the development of novel
      imaging techniques, which are capable of characterizing vascular pathology in
      vivo. They provide vascular structural read-outs and have the ability to assess
      the functional consequences of vascular dysfunction as well as to visualize and
      monitor the molecular processes underlying these pathological alterations. This
      article focusses on recent in vivo small animal imaging studies addressing
      vascular aspects related to AD. With the technical advances of imaging modalities
      such as magnetic resonance, nuclear and microscopic imaging, molecular,
      functional and structural information related to vascular pathology can now be
      visualized in vivo in small rodents. Imaging vascular and parenchymal amyloid
      beta (Abeta) deposition as well as Abeta transport pathways have been shown to be
      useful to characterize their dynamics and to elucidate their role in the
      development of cerebral amyloid angiopathy and AD. Structural and functional
      imaging read-outs have been employed to describe the deleterious affects of Abeta
      on vessel morphology, hemodynamics and vascular integrity. More recent imaging
      studies have also addressed how inflammatory processes partake in the
      pathogenesis of the disease. Moreover, imaging can be pivotal in the search for
      novel therapies targeting the vasculature. 

PMID- 24659969
TI  - Labile iron in cells and body fluids: physiology, pathology, and pharmacology.
AB  - In living systems iron appears predominantly associated with proteins, but can
      also be detected in forms referred as labile iron, which denotes the combined
      redox properties of iron and its amenability to exchange between ligands,
      including chelators. The labile cell iron (LCI) composition varies with metal
      concentration and substances with chelating groups but also with pH and the
      medium redox potential. Although physiologically in the lower MUM range, LCI
      plays a key role in cell iron economy as cross-roads of metabolic pathways. LCI
      levels are continually regulated by an iron-responsive machinery that balances
      iron uptake versus deposition into ferritin. However, LCI rises aberrantly in
      some cell types due to faulty cell utilization pathways or infiltration by
      pathological iron forms that are found in hemosiderotic plasma. As LCI attains
      pathological levels, it can catalyze reactive O species (ROS) formation that, at
      particular threshold, can surpass cellular anti-oxidant capacities and seriously
      damage its constituents. While in normal plasma and interstitial fluids,
      virtually all iron is securely carried by circulating transferrin (Tf; that
      renders iron essentially non-labile), in systemic iron overload (IO), the total
      plasma iron binding capacity is often surpassed by a massive iron influx from
      hyperabsorptive gut or from erythrocyte overburdened spleen and/or liver. As
      plasma Tf approaches iron saturation, labile plasma iron (LPI) emerges in forms
      that can infiltrate cells by unregulated routes and raise LCI to toxic levels.
      Despite the limited knowledge available on LPI speciation in different types and
      degrees of IO, LPI measurements can be and are in fact used for identifying
      systemic IO and for initiating/adjusting chelation regimens to attain full-day
      LPI protection. A recent application of labile iron assay is the detection of
      labile components in intravenous iron formulations per se as well as in plasma
      (LPI) following parenteral iron administration. 

PMID- 24659970
TI  - Mating changes the female dietary preference in the two-spotted cricket, Gryllus
      bimaculatus.
AB  - Most insect species exhibit characteristic behavioral changes after mating.
      Typical post-mating behaviors in female insects include noticeable increases in
      food intake, elevated oviposition rates, lowered receptivity to courting males,
      and enhanced immune response. Although it has been reported that mated females of
      several insect species including the fruit fly, Drosophila melanogaster increase
      the amount of food intake and change their dietary preferences, the limited
      number of comparative studies prevent the formulation of generalities regarding
      post-mating behaviors in other insects in particular amongst orthopteran species.
      Here, we investigated whether females of the two-spotted cricket, Gryllus
      bimaculatus, alter their feeding behavior after mating. Although significant
      differences in the amount of food intake after mating were not observed, all
      experimental data indicated a clear trend among crickets toward the ingestion of
      larger quantities of food. Geometric framework analyses revealed that the mated
      female crickets preferred food with higher protein content compared to virgin
      female crickets. This implies that this species required different nutritional
      demands after mating. These findings further expand our understanding of the
      behavioral and biological changes that are triggered in female insects post
      mating, and highlight the potential for this species in investigating the
      molecular-based nutritional dependent activities that are linked to post-mating
      behaviors. 

PMID- 24659971
TI  - Targeting diseased tissues by pHLIP insertion at low cell surface pH.
AB  - The discovery of the pH Low Insertion Peptides (pHLIPs(r)) provides an
      opportunity to develop imaging and drug delivery agents targeting extracellular
      acidity. Extracellular acidity is associated with many pathological states, such
      as those in cancer, ischemic stroke, neurotrauma, infection, lacerations, and
      others. The metabolism of cells in injured or diseased tissues often results in
      the acidification of the extracellular environment, so acidosis might be useful
      as a general marker for the imaging and treatment of diseased states if an
      effective targeting method can be developed. The molecular mechanism of a pHLIP
      peptide is based on pH-dependent membrane-associated folding. pHLIPs, being
      moderately hydrophobic peptides, have high affinities for cellular membranes at
      normal pH, but fold and insert across membranes at low pH, allowing them to sense
      pH at the surfaces of cells in diseased tissues, where it is the lowest. Here we
      discuss the main principles of pHLIP interactions with membrane lipid bilayers at
      neutral and low pHs, the possibility of tuning the folding and insertion pH by
      peptide sequence variation, and potential applications of pHLIPs for imaging,
      therapy and image-guided interventions. 

PMID- 24659972
TI  - The representation of material categories in the brain.
AB  - Using textures mapped onto virtual nonsense objects, it has recently been shown
      that early visual cortex plays an important role in processing material
      properties. Here, we examined brain activation to photographs of materials,
      consisting of wood, stone, metal and fabric surfaces. These photographs were
      close-ups in the sense that the materials filled the image. In the first
      experiment, observers categorized the material in each image (i.e., wood, stone,
      metal, or fabric), while in an fMRI-scanner. We predicted the assigned material
      category using the obtained voxel patterns using a linear classifier. Region-of
      interest and whole-brain analyses demonstrated material coding in the early
      visual regions, with lower accuracies for more anterior regions. There was little
      evidence for material coding in other brain regions. In the second experiment, we
      used an adaptation paradigm to reveal additional brain areas involved in the
      perception of material categories. Participants viewed images of wood, stone,
      metal, and fabric, presented in blocks with images of either different material
      categories (no adaptation) or images of different samples from the same material
      category (material adaptation). To measure baseline activation, blocks with the
      same material sample were presented (baseline adaptation). Material adaptation
      effects were found mainly in the parahippocampal gyrus, in agreement with fMRI
      studies of texture perception. Our findings suggest that the parahippocampal
      gyrus, early visual cortex, and possibly the supramarginal gyrus are involved in
      the perception of material categories, but in different ways. The different
      outcomes from the two studies are likely due to inherent differences between the
      two paradigms. A third experiment suggested, based on anatomical overlap between
      activations, that spatial frequency information is important for within-category
      material discrimination. 

PMID- 24659973
TI  - When all children comprehend: increasing the external validity of narrative
      comprehension development research.
AB  - Narratives, also called stories, can be found in conversations, children's play
      interactions, reading material, and television programs. From infancy to
      adulthood, narrative comprehension processes interpret events and inform our
      understanding of physical and social environments. These processes have been
      extensively studied to ascertain the multifaceted nature of narrative
      comprehension. From this research we know that three overlapping processes (i.e.,
      knowledge integration, goal structure understanding, and causal inference
      generation) proposed by the constructionist paradigm are necessary for narrative
      comprehension, narrative comprehension has a predictive relationship with
      children's later reading performance, and comprehension processes are
      generalizable to other contexts. Much of the previous research has emphasized
      internal and predictive validity; thus, limiting the generalizability of previous
      findings. We are concerned these limitations may be excluding underrepresented
      populations from benefits and implications identified by early comprehension
      processes research. This review identifies gaps in extant literature regarding
      external validity and argues for increased emphasis on externally valid research.
      We highlight limited research on narrative comprehension processes in children
      from low-income and minority populations, and argue for changes in comprehension
      assessments. Specifically, we argue both on- and off-line assessments should be
      used across various narrative types (e.g., picture books, televised narratives)
      with traditionally underserved and underrepresented populations. We propose
      increasing the generalizability of narrative comprehension processes research can
      inform persistent reading achievement gaps, and have practical implications for
      how children learn from narratives. 

PMID- 24659974
TI  - Obsessive-compulsive disorder patients have a reduced sense of control on the
      illusion of control task.
AB  - There is disagreement regarding the role of perceived control in obsessive
      compulsive disorder (OCD). The present study used a traditional illusion of
      control paradigm (Alloy and Abramson, 1979) to empirically test control
      estimation in OCD. Twenty-six OCD patients and 26 matched comparison subjects
      completed an illusion of control task wherein their goal was to attempt to exert
      control over a light bulb. The density of reinforcement (high, low) and the
      valence of trials (gain, loss) were experimentally manipulated within subjects.
      Unbeknownst to participants, the illumination of the light bulb was predetermined
      and irrespective of their behavior. OCD patients exhibited lower estimates of
      control compared with healthy comparison subjects. There were no interactions
      between group and outcome density or group and valence. We found that OCD
      patients endorse lower estimates of control than comparison subjects. This
      finding highlights a potential role for contingency learning in the disorder. 

PMID- 24659975
TI  - Predictors of cognitive enhancement after training in preschoolers from diverse
      socioeconomic backgrounds.
AB  - The association between socioeconomic status and child cognitive development, and
      the positive impact of interventions aimed at optimizing cognitive performance,
      are well-documented. However, few studies have examined how specific socio
      environmental factors may moderate the impact of cognitive interventions among
      poor children. In the present study, we examined how such factors predicted
      cognitive trajectories during the preschool years, in two samples of children
      from Argentina, who participated in two cognitive training programs (CTPs)
      between the years 2002 and 2005: the School Intervention Program (SIP; N = 745)
      and the Cognitive Training Program (CTP; N = 333). In both programs children were
      trained weekly for 16 weeks and tested before and after the intervention using a
      battery of tasks assessing several cognitive control processes (attention,
      inhibitory control, working memory, flexibility and planning). After applying
      mixed model analyses, we identified sets of socio-environmental predictors that
      were associated with higher levels of pre-intervention cognitive control
      performance and with increased improvement in cognitive control from pre- to post
      intervention. Child age, housing conditions, social resources, parental
      occupation and family composition were associated with performance in specific
      cognitive domains at baseline. Housing conditions, social resources, parental
      occupation, family composition, maternal physical health, age, group
      (intervention/control) and the number of training sessions were related to
      improvements in specific cognitive skills from pre- to post-training. 

PMID- 24659976
TI  - The interplay between the anticipation and subsequent online processing of
      emotional stimuli as measured by pupillary dilatation: the role of cognitive
      reappraisal.
AB  - Emotions can occur during an emotion-eliciting event, but they can also arise
      when anticipating the event. We used pupillary responses, as a measure of
      effortful cognitive processing, to test whether the anticipation of an emotional
      stimulus (positive and negative) influences the subsequent online processing of
      that emotional stimulus. Moreover, we tested whether individual differences in
      the habitual use of emotion regulation strategies are associated with pupillary
      responses during the anticipation and/or online processing of this emotional
      stimulus. Our results show that, both for positive and negative stimuli,
      pupillary diameter during the anticipation of emotion-eliciting events is
      inversely and strongly correlated to pupillary responses during the emotional
      image presentation. The variance in this temporal interplay between anticipation
      and online processing was related to individual differences in emotion
      regulation. Specifically, the results show that high reappraisal scores are
      related to larger pupil diameter during the anticipation which is related to
      smaller pupillary responses during the online processing of emotion-eliciting
      events. The habitual use of expressive suppression was not associated to
      pupillary responses in the anticipation and subsequent online processing of
      emotional stimuli. Taken together, the current data suggest (most strongly for
      individuals scoring high on the habitual use of reappraisal) that larger
      pupillary responses during the anticipation of an emotional stimulus are
      indicative of a sustained attentional set activation to prepare for an upcoming
      emotional stimulus, which subsequently directs a reduced need to cognitively
      process that emotional event. Hence, because the habitual use of reappraisal is
      known to have a positive influence on emotional well-being, the interplay between
      anticipation and online processing of emotional stimuli might be a significant
      marker of this well-being. 

PMID- 24659977
TI  - Slow time perception can be learned.

PMID- 24659979
TI  - Modeling causal conditional reasoning data using SDT: caveats and new insights.

PMID- 24659978
TI  - Food-cue affected motor response inhibition and self-reported dieting success: a
      pictorial affective shifting task.
AB  - Behavioral inhibition is one of the basic facets of executive functioning and is
      closely related to self-regulation. Impulsive reactions, that is, low inhibitory
      control, have been associated with higher body mass index (BMI), binge eating,
      and other problem behaviors (e.g., substance abuse, pathological gambling, etc.).
      Nevertheless, studies which investigated the direct influence of food-cues on
      behavioral inhibition have been fairly inconsistent. In the current studies, we
      investigated food-cue affected behavioral inhibition in young women. For this
      purpose, we used a go/no-go task with pictorial food and neutral stimuli in which
      stimulus-response mapping is reversed after every other block (affective shifting
      task). In study 1, hungry participants showed faster reaction times to and
      omitted fewer food than neutral targets. Low dieting success and higher BMI were
      associated with behavioral disinhibition in food relative to neutral blocks. In
      study 2, both hungry and satiated individuals were investigated. Satiation did
      not influence overall task performance, but modulated associations of task
      performance with dieting success and self-reported impulsivity. When satiated,
      increased food craving during the task was associated with low dieting success,
      possibly indicating a preload-disinhibition effect following food intake. Food
      cues elicited automatic action and approach tendencies regardless of dieting
      success, self-reported impulsivity, or current hunger levels. Yet, associations
      between dieting success, impulsivity, and behavioral food-cue responses were
      modulated by hunger and satiation. Future research investigating clinical samples
      and including other salient non-food stimuli as control category is warranted. 

PMID- 24659980
TI  - Task-evoked pupillometry provides a window into the development of short-term
      memory capacity.
AB  - The capacity to keep multiple items in short-term memory (STM) improves over
      childhood and provides the foundation for the development of multiple cognitive
      abilities. The goal of this study was to measure the extent to which age
      differences in STM capacity are related to differences in task engagement during
      encoding. Children (n = 69, mean age = 10.6 years) and adults (n = 54, mean age =
      27.5 years) performed two STM tasks: the forward digit span test from the
      Wechsler Intelligence Scale for Children (WISC) and a novel eyetracking digit
      span task designed to overload STM capacity. Building on prior research showing
      that task-evoked pupil dilation can be used as a real-time index of task
      engagement, we measured changes in pupil dilation while participants encoded long
      sequences of digits for subsequent recall. As expected, adults outperformed
      children on both STM tasks. We found similar patterns of pupil dilation while
      children and adults listened to the first six digits on our STM overload task,
      after which the adults' pupils continued to dilate and the children's began to
      constrict, suggesting that the children had reached their cognitive limits and
      that they had begun to disengage from the task. Indeed, the point at which pupil
      dilation peaked at encoding was a significant predictor of WISC forward span, and
      this relationship held even after partialing out recall performance on the STM
      overload task. These findings indicate that sustained task engagement at encoding
      is an important component of the development of STM. 

PMID- 24659981
TI  - From is to ought, and back: how normative concerns foster progress in reasoning
      research.

PMID- 24659982
TI  - Is it inevitable that societies exploit useful technologies?

PMID- 24659983
TI  - Magnetic vestibular stimulation in subjects with unilateral labyrinthine
      disorders.
AB  - We recently discovered that static magnetic fields from high-strength MRI
      machines induce nystagmus in all normal humans, and that a magneto-hydrodynamic
      Lorentz force, derived from ionic currents in the endolymph and pushing on the
      cupula, best explains this effect. Individuals with no labyrinthine function have
      no nystagmus. The influence of magnetic vestibular stimulation (MVS) in
      individuals with unilateral deficits in labyrinthine function is unknown and may
      provide insight into the mechanism of MVS. These individuals should experience
      MVS, but with a different pattern of nystagmus consistent with their unilateral
      deficit in labyrinthine function. We recorded eye movements in the static
      magnetic field of a 7 T MRI machine in nine individuals with unilateral
      labyrinthine hypofunction, as determined by head impulse testing and vestibular
      evoked myogenic potentials (VEMP). Eye movements were recorded using infrared
      video-oculography. Static head positions were varied in pitch with the body
      supine, and slow-phase eye velocity (SPV) was assessed. All subjects exhibited
      predominantly horizontal nystagmus after entering the magnet head-first, lying
      supine. The SPV direction reversed when entering feet-first. Pitching chin-to
      chest caused subjects to reach a null point for horizontal SPV. Right unilateral
      vestibular hypofunction (UVH) subjects developed slow-phase-up nystagmus and left
      UVH subjects, slow-phase-down nystagmus. Vertical and torsional components were
      consistent with superior semicircular canal excitation or inhibition,
      respectively, of the intact ear. These findings provide compelling support for
      the hypothesis that MVS is a result of a Lorentz force and suggest that the
      function of individual structures within the labyrinth can be assessed with MVS.
      As a novel method of comfortable and sustained labyrinthine stimulation, MVS can
      provide new insights into vestibular physiology and pathophysiology. 

PMID- 24659984
TI  - Reduced Glycemic Variability in Diazoxide-Responsive Children with Congenital
      Hyperinsulinism Using Supplemental Omega-3-Polyunsaturated Fatty Acids; A Pilot
      Trial with MaxEPA(R.).
AB  - OBJECTIVE: Congenital hyperinsulinism (CHI) is a rare condition of hypoglycemia
      where therapeutic options are limited and often complicated by side-effects.
      Omega-3-polyunsaturated fatty acids (PUFA), which can suppress cardiac myocyte
      electrical activity, may also reduce ion channel activity in insulin-secreting
      cells. PUFA supplements in combination with standard medical treatment may
      improve glucose profile and may reduce glycemic variability in diazoxide
      responsive CHI. DESIGN: Open label pilot trial with MaxEPA(R) liquid
      (eicosapentaenoic and docosahexaenoic acid) PUFA (3 ml/day for 21 days) in
      diazoxide-responsive CHI patients (https://eudract.ema.europa.eu/, EudraCT number
      201100363333). METHODS: Glucose levels were monitored pre-treatment, end of
      treatment, and at follow-up by subcutaneous continuous glucose monitoring systems
      (CGMS) in 13 patients (7 girls) who received PUFA. Outcome measures were an
      improved glucose profile, reduced glycemic variability quantified by a reduction
      in the frequency of glucose levels <4 and >10 mmol/l, and safety of PUFA. All
      children were analyzed either as intention to treat (n = 13) or as per protocol
      (n = 7). RESULTS: Mean (%) CGMS glucose levels increased by 0.1 mmol/l (2%) in
      intention to treat and by 0.4 mmol/l (8%) in per protocol analysis (n = 7). The
      frequency of CGMS <4 mmol/l was significantly less at the end of treatment than
      in the pre-treatment period [556 (7%) vs. 749 (10%)]. Similarly, the frequency of
      CGMS >10 mmol/l, was also less at the end of treatment [27 (0.3%) vs. 49 (0.7%)].
      Except for one child with increased LDL cholesterol, all safety parameters were
      normal. CONCLUSION: MaxEPA(R) was safe and reduced glycemic variability, but did
      not increase glucose profiles significantly in diazoxide-responsive CHI. The
      supplemental value of PUFA should be evaluated in a comprehensive clinical trial.

PMID- 24659985
TI  - Hormonal Fluctuations during the Estrous Cycle Modulate Heme Oxygenase-1
      Expression in the Uterus.
AB  - Deletion of the heme oxygenase-1 (HO-1) (Hmox1) locus in mice results in
      intrauterine lethality. The expression of the heme catabolizing enzyme encoded by
      this gene, namely HO-1, is required to successfully support reproductive events.
      We have previously observed that HO-1 acts at several key events in reproduction
      ensuring pregnancy. HO-1 defines ovulation, positively influences implantation
      and placentation, and ensures fetal growth and survival. Here, we embarked on a
      study aimed to determine whether hormonal changes during the estrous cycle in the
      mouse define HO-1 expression that may influence receptivity. We analyzed the
      serum levels of progesterone and estrogen by ELISA and HO-1 mRNA expression in
      uterus by real time RT-PCR at the metestrus, proestrus, estrus, and diestrus
      phases of the estrous cycle. Further, we studied the HO-1 protein expression by
      western blot upon hormone addition to cultured uterine AN3 cells. We observed
      that HO-1 variations in uterine tissue correlated to changes in hormonal levels
      at different phases of the estrus cycle. In vitro, HO-1 protein levels in AN3
      cells augmented after the addition of physiological concentrations of
      progesterone and estradiol, which confirmed our in vivo observations. Our data
      suggest an important role for hormones in HO-1 regulation in uterus during
      receptivity, a process known to have a significant impact in receptivity and
      later on blastocyst implantation. 

PMID- 24659986
TI  - A Glimpse of the genomic diversity of haloarchaeal tailed viruses.
AB  - Tailed viruses are the most common isolates infecting prokaryotic hosts residing
      in hypersaline environments. Archaeal tailed viruses represent only a small
      portion of all characterized tailed viruses of prokaryotes. But even this small
      dataset revealed that archaeal tailed viruses have many similarities to their
      counterparts infecting bacteria, the bacteriophages. Shared functional homologs
      and similar genome organizations suggested that all microbial tailed viruses have
      common virion architectural and assembly principles. Recent structural studies
      have provided evidence justifying this thereby grouping archaeal and bacterial
      tailed viruses into a single lineage. Currently there are 17 haloarchaeal tailed
      viruses with entirely sequenced genomes. Nine viruses have at least one close
      relative among the 17 viruses and, according to the similarities, can be divided
      into three groups. Two other viruses share some homologs and therefore are
      distantly related, whereas the rest of the viruses are rather divergent (or
      singletons). Comparative genomics analysis of these viruses offers a glimpse into
      the genetic diversity and structure of haloarchaeal tailed virus communities. 

PMID- 24659987
TI  - Effects of different compost amendments on the abundance and composition of alkB
      harboring bacterial communities in a soil under industrial use contaminated with
      hydrocarbons.
AB  - Alkane degrading microorganisms play an important role for the bioremediation of
      petrogenic contaminated environments. In this study, we investigated the effects
      of compost addition on the abundance and diversity of bacteria harboring the
      alkane monooxygenase gene (alkB) in an oil-contaminated soil originated from an
      industrial zone in Celje, Slovenia (Technosol). Soil without any amendments
      (control soil) and soil amended with two composts differing in their maturation
      stage and nutrient availability, were incubated under controlled conditions in a
      microcosm experiment and sampled after 0, 6, 12, and 36 weeks of incubation. As
      expected the addition of compost stimulated the degradation of alkanes in the
      investigated soil shortly after the addition. By using quantitative real-time PCR
      higher number of alkB genes were detected in soil samples amended with compost
      compared to the control soils. To get an insight into the composition of alkB
      harboring microbial communities, we performed next generation sequencing of
      amplicons of alkB gene fragment. Richness and diversity of alkB gene harboring
      prokaryotes was higher in soil mixed with compost compared to control soils with
      stronger effects of the less maturated, nutrient poor compost. The phylogenetic
      analysis of communities suggested that the addition of compost stimulated the
      abundance of alkB harboring Actinobacteria during the experiment independent from
      the maturation stage of the compost. AlkB harboring gamma-proteobacteria like
      Shewanella or Hydrocarboniphaga as well as alpha-proteobacteria of the genus
      Agrobacterium responded also positively to the addition of compost to soil. The
      amendment of the less maturated, nutrient poor compost resulted in addition in a
      large increase of alkB harboring bacteria of the Cytophaga group (Microscilla)
      mainly at the early sampling time points. Our data indicates that compost
      amendments significantly change abundance and diversity pattern of alkB harboring
      microbes in Technosol and might be a useful agent to stimulate bioremediation of
      hydrocarbons in contaminated soils. 

PMID- 24659988
TI  - Temperate Streptococcus thermophilus phages expressing superinfection exclusion
      proteins of the Ltp type.
AB  - Lipoprotein Ltp encoded by temperate Streptococcus thermophilus phage TP-J34 is
      the prototype of the wide-spread family of host cell surface-exposed lipoproteins
      involved in superinfection exclusion (sie). When screening for other S.
      thermophilus phages expressing this type of lipoprotein, three temperate phages
      TP-EW, TP-DSM20617, and TP-778-were isolated. In this communication we present
      the total nucleotide sequences of TP-J34 and TP-778L. For TP-EW, a phage almost
      identical to TP-J34, besides the ltp gene only the two regions of deviation from
      TP-J34 DNA were analyzed: the gene encoding the tail protein causing an assembly
      defect in TP-J34 and the gene encoding the lysin, which in TP-EW contains an
      intron. For TP-DSM20617 only the sequence of the lysogeny module containing the
      ltp gene was determined. The region showed high homology to the same region of TP
      778. For TP-778 we could show that absence of the attR region resulted in
      aberrant excision of phage DNA. The amino acid sequence of mature LtpTP-EW was
      shown to be identical to that of mature LtpTP-J34, whereas the amino acid
      sequence of mature LtpTP-778 was shown to differ from mature LtpTP-J34 in eight
      amino acid positions. LtpTP-DSM20617 was shown to differ from LtpTP-778 in just
      one amino acid position. In contrast to LtpTP-J34, LtpTP-778 did not affect
      infection of lactococcal phage P008 instead increased activity against phage P001
      was noticed. 

PMID- 24659989
TI  - Autophagy in plasma cell pathophysiology.
AB  - Plasma cells (PCs) are the effectors responsible for antibody (Ab)-mediated
      immunity. They differentiate from B lymphocytes through a complete remodeling of
      their original structure and function. Stress is a constitutive element of PC
      differentiation. Macroautophagy, conventionally referred to as autophagy, is a
      conserved lysosomal recycling strategy that integrates cellular metabolism and
      enables adaptation to stress. In metazoa, autophagy plays diverse roles in cell
      differentiation. Recently, a number of autophagic functions have been recognized
      in innate and adaptive immunity, including clearance of intracellular pathogens,
      inflammasome regulation, lymphocyte ontogenesis, and antigen presentation. We
      identified a previously unrecognized role played by autophagy in PC
      differentiation and activity. Following B cell activation, autophagy moderates
      the expression of the transcriptional repressor Blimp-1 and immunoglobulins
      through a selective negative control exerted on the size of the endoplasmic
      reticulum and its stress signaling response, including the essential PC
      transcription factor, XBP-1. This containment of PC differentiation and function,
      i.e., Ab production, is essential to optimize energy metabolism and viability. As
      a result, autophagy sustains Ab responses in vivo. Moreover, autophagy is an
      essential intrinsic determinant of long-lived PCs in their as yet poorly
      understood bone marrow niche. In this essay, we discuss these findings in the
      context of the established biological functions of autophagy, and their manifold
      implications for adaptive immunity and PC diseases, in primis multiple myeloma. 

PMID- 24659990
TI  - Expression of paralogous SEP-, FUL-, AG- and STK-like MADS-box genes in wild-type
      and peloric Phalaenopsis flowers.
AB  - The diverse flowers of Orchidaceae are the result of several major morphological
      transitions, among them the most studied is the differentiation of the inner
      median tepal into the labellum, a perianth organ key in pollinator attraction.
      Type A peloria lacking stamens and with ectopic labella in place of inner lateral
      tepals are useful for testing models on the genes specifying these organs by
      comparing their patterns of expression between wild-type and peloric flowers.
      Previous studies focused on DEFICIENS- and GLOBOSA-like MADS-box genes because of
      their conserved role in perianth and stamen development. The "orchid code" model
      summarizes this work and shows in Orchidaceae there are four paralogous lineages
      of DEFICIENS/AP3-like genes differentially expressed in each floral whorl.
      Experimental tests of this model showed the conserved, higher expression of genes
      from two specific DEF-like gene lineages is associated with labellum development.
      The present study tests whether eight MADS-box candidate SEP-, FUL-, AG-, and STK
      like genes have been specifically duplicated in the Orchidaceae and are also
      differentially expressed in association with the distinct flower organs of
      Phalaenopsis hyb. "Athens." The gene trees indicate orchid-specific duplications.
      In a way analogous to what is observed in labellum-specific DEF-like genes, a two
      fold increase in the expression of SEP3-like gene PhaMADS7 was measured in the
      labellum-like inner lateral tepals of peloric flowers. The overlap between SEP3
      like and DEF-like genes suggests both are associated with labellum specification
      and similar positional cues determine their domains of expression. In contrast,
      the uniform messenger levels of FUL-like genes suggest they are involved in the
      development of all organs and their expression in the ovary suggests cell
      differentiation starts before pollination. As previously reported AG-like and STK
      like genes are exclusively expressed in gynostemium and ovary, however no
      evidence for transcriptional divergence was found in the stage investigated. Gene
      expression suggests a developmental regulatory system based on the combined
      activity of duplicate MADS-box genes. We discuss its feasibility based on
      documented protein interactions and patterns of expression. 

PMID- 24659991
TI  - Dynamic regulation and function of histone monoubiquitination in plants.
AB  - Polyubiquitin chain deposition on a target protein frequently leads to proteasome
      mediated degradation whereas monoubiquitination modifies target protein property
      and function independent of proteolysis. Histone monoubiquitination occurs in
      chromatin and is in nowadays recognized as one critical type of epigenetic marks
      in eukaryotes. While H2A monoubiquitination (H2Aub1) is generally associated with
      transcription repression mediated by the Polycomb pathway, H2Bub1 is involved in
      transcription activation. H2Aub1 and H2Bub1 levels are dynamically regulated via
      deposition and removal by specific enzymes. We review knows and unknowns of
      dynamic regulation of H2Aub1 and H2Bub1 deposition and removal in plants and
      highlight the underlying crucial functions in gene transcription, cell
      proliferation/differentiation, and plant growth and development. We also discuss
      crosstalks existing between H2Aub1 or H2Bub1 and different histone methylations
      for an ample mechanistic understanding. 

PMID- 24659992
TI  - Distinct phylogenetic relationships and biochemical properties of Arabidopsis
      ovarian tumor-related deubiquitinases support their functional differentiation.
AB  - The reverse reaction of ubiquitylation is catalyzed by different classes of
      deubiquitylation enzymes (DUBs), including ovarian tumor domain (OTU)-containing
      DUBs; experiments using Homo sapiens proteins have demonstrated that OTU DUBs
      modulate various cellular processes. With the exception of OTLD1, plant OTU DUBs
      have not been characterized. We identified 12 Arabidopsis thaliana OTU loci and
      analyzed 11 of the encoded proteins in vitro to determine their preferences for
      the ubiquitin (UB) chains of M1, K48, and K63 linkages as well as the UB-/RUB
      /SUMO-GST fusions. The A. thaliana OTU DUBs were shown to be cysteine proteases
      and classified into four groups with distinct linkage preferences: OTU1 (M1 = K48
      > K63), OTU3/4/7/10 (K63 > K48 > M1), OTU2/9 (K48 = K63), and OTU5/11/12/OTLD1
      (inactive). Five active OTU DUBs (OTU3/4/7/9/10) also cleaved RUB fusion.
      OTU1/3/4 cleaved M1 UB chains, suggesting a possible role for M1 chains in plant
      cellular signaling. The different substrate specificities of the various A.
      thaliana OTU DUBs indicate the involvement of distinct structural elements; for
      example, the OTU1 oxyanion residue D89 is essential for cleaving isopeptide bond
      linked chains but dispensable for M1 chains. UB-binding activities were detected
      only for OTU2 and OTLD1, with distinct linkage preferences. These differences in
      biochemical properties support the involvement of A. thaliana OTU DUBs in
      different functions. Moreover, based on the established phylogenetic tree, plant-
      and H. sapiens-specific clades exist, which suggests that the proteins within
      these clades have taxa-specific functions. We also detected five OTU clades that
      are conserved across species, which suggests that the orthologs in different
      species within each clade are involved in conserved cellular processes, such as
      ERAD and DNA damage responses. However, different linkage preferences have been
      detected among potential cross-species OTU orthologs, indicating functional and
      mechanistic differentiation. 

PMID- 24659993
TI  - Response of plants to water stress.
AB  - Water stress adversely impacts many aspects of the physiology of plants,
      especially photosynthetic capacity. If the stress is prolonged, plant growth, and
      productivity are severely diminished. Plants have evolved complex physiological
      and biochemical adaptations to adjust and adapt to a variety of environmental
      stresses. The molecular and physiological mechanisms associated with water-stress
      tolerance and water-use efficiency have been extensively studied. The systems
      that regulate plant adaptation to water stress through a sophisticated regulatory
      network are the subject of the current review. Molecular mechanisms that plants
      use to increase stress tolerance, maintain appropriate hormone homeostasis and
      responses and prevent excess light damage, are also discussed. An understanding
      of how these systems are regulated and ameliorate the impact of water stress on
      plant productivity will provide the information needed to improve plant stress
      tolerance using biotechnology, while maintaining the yield and quality of crops. 

PMID- 24659994
TI  - Dissecting the molecular mechanism underlying the intimate relationship between
      cellulose microfibrils and cortical microtubules.
AB  - A central question in plant cell development is how the cell wall determines
      directional cell expansion and therefore the final shape of the cell. As the
      major load-bearing component of the cell wall, cellulose microfibrils are laid
      down transversely to the axis of elongation, thus forming a spring-like structure
      that reinforces the cell laterally and while favoring longitudinal expansion in
      most growing cells. Mounting evidence suggests that cortical microtubules
      organize the deposition of cellulose microfibrils, but the precise molecular
      mechanisms linking microtubules to cellulose organization have remained unclear
      until the recent discovery of cellulose synthase interactive protein 1 , a linker
      protein between the cortical microtubules and the cellulose biosynthesizing
      machinery. In this review, we will focus on the intimate relationship between
      cellulose microfibrils and cortical microtubules, in particular, we will discuss
      microtubule arrangement and cell wall architecture, the linkage between cellulose
      synthase complexes and microtubules, and the feedback mechanisms between cell
      wall and microtubules. 

PMID- 24659995
TI  - Regulation of root hair cell differentiation by R3 MYB transcription factors in
      tomato and Arabidopsis.
AB  - CAPRICE (CPC) encodes a small protein with an R3 MYB motif and regulates root
      hair and trichome cell differentiation in Arabidopsis thaliana. Six additional
      CPC-like MYB proteins including TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC1
      (ETC1), ENHANCER OF TRY AND CPC2 (ETC2), ENHANCER OF TRY AND CPC3/CPC-LIKE MYB3
      (ETC3/CPL3), TRICHOMELESS1 (TCL1), and TRICHOMELESS2/CPC-LIKE MYB4 (TCL2/CPL4)
      also have the ability to regulate root hair and/or trichome cell differentiation
      in Arabidopsis. In this review, we describe our latest findings on how CPC-like
      MYB transcription factors regulate root hair cell differentiation. Recently, we
      identified the tomato SlTRY gene as an ortholog of the Arabidopsis TRY gene.
      Transgenic Arabidopsis plants harboring SlTRY produced more root hairs, a
      phenotype similar to that of 35S::CPC transgenic plants. CPC is also known to be
      involved in anthocyanin biosynthesis. Anthocyanin accumulation was repressed in
      the SlTRY transgenic plants, suggesting that SlTRY can also influence anthocyanin
      biosynthesis. We concluded that tomato and Arabidopsis partially use similar
      transcription factors for root hair cell differentiation, and that a CPC-like R3
      MYB may be a key common regulator of plant root-hair development. 

PMID- 24659996
TI  - Biological noise to get a sense of direction: an analogy between chemotaxis and
      stress response.

PMID- 24659997
TI  - A framework for the objective assessment of registration accuracy.
AB  - Validation and accuracy assessment are the main bottlenecks preventing the
      adoption of image processing algorithms in the clinical practice. In the
      classical approach, a posteriori analysis is performed through objective metrics.
      In this work, a different approach based on Petri nets is proposed. The basic
      idea consists in predicting the accuracy of a given pipeline based on the
      identification and characterization of the sources of inaccuracy. The concept is
      demonstrated on a case study: intrasubject rigid and affine registration of
      magnetic resonance images. Both synthetic and real data are considered. While
      synthetic data allow the benchmarking of the performance with respect to the
      ground truth, real data enable to assess the robustness of the methodology in
      real contexts as well as to determine the suitability of the use of synthetic
      data in the training phase. Results revealed a higher correlation and a lower
      dispersion among the metrics for simulated data, while the opposite trend was
      observed for pathologic ones. Results show that the proposed model not only
      provides a good prediction performance but also leads to the optimization of the
      end-to-end chain in terms of accuracy and robustness, setting the ground for its
      generalization to different and more complex scenarios. 

PMID- 24659998
TI  - Concentration of cd, pb, hg, and se in different parts of human breast cancer
      tissues.
AB  - Breast cancer is the major cause of cancer morbidity and mortality between women
      in the world. Metals involved in environmental toxicology are closely related to
      tumor growth and cancer. On the other hand, some metals such as selenium have
      anticarcinogenic properties. The aim of this study is to determine the
      concentration of cadmium, lead, mercury, and selenium in separated parts of
      tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues
      which have been analyzed by graphite furnace atomic absorption (AA-670) and ICP
      OES (ULTIMA 2CE). Our results show that Se and Hg have maximum and minimum
      concentration, respectively. Statistical analysis reveals no significant
      differences between metal accumulations in different parts of cancer tissues (P >
      0.05) and this observation might be due to the close relation of separated parts
      of fatty breast organ. Thus, we could conclude that a high level of these heavy
      metals is accumulated in Iranian cancerous breasts and their presence can be one
      of the reasons of cancer appearance. 

PMID- 24659999
TI  - Nuclear pattern of CXCR4 expression is associated with a better overall survival
      in patients with gastric cancer.
AB  - Introduction. Previous studies have shown that stromal-derived factor-1 (CXCL12)
      and its receptor, CXCR4, play a crucial role in metastasis of various tumors.
      Similarly, it has been cleared that CXCR4 is expressed on the cell surface of
      gastric cancers. However, nuclear expression of CXCR4 and its clinical importance
      have not been yet studied. Materials and Methods. Herein, we studied the
      expression of CXCR4 in gastric samples from patients with gastric adenocarcinoma
      as well as human gastric carcinoma cell line, AGS, by employing RT-PCR,
      immunohistochemistry, and flow cytometry techniques. Results. RT-PCR data showed
      that CXCR4 is highly expressed on AGS cells. This was confirmed by IHC and FACS
      as CXCR4 was detected on cell membrane, in cytoplasm, and in nucleus of AGS
      cells. Moreover, we found that both cytoplasmic and nuclear CXCR4 are strongly
      expressed in primary gastric cancer and the cytoplasmic pattern of CXCR4 tends to
      be associated with a shorter overall survival than nuclear staining. In
      conclusion, we present evidence for the first time that both cytoplasmic and
      nuclear expression of CXCR4 are detectable in gastric cancer tissues. However,
      the role of both cytoplasmic and nuclear CXCR4 needs to be further elucidated. 

PMID- 24660000
TI  - In vitro whole blood clot lysis for fibrinolytic activity study using d-dimer and
      confocal microscopy.
AB  - This study aimed to evaluate in vitro whole blood (WB) clot lysis method for the
      assessment of fibrinolytic activity. Standardized unresected (uncut) retracted WB
      clot was incubated in pool platelet poor plasma (PPP) for varying incubation
      times and in streptokinase (SK) at different concentrations. The fibrinolytic
      activity was assessed by D-dimer (DD), confocal microscopy, and clot weight. DD
      was measured photometrically by immunoturbidimetric method. There was a
      significant difference in mean DD levels according to SK concentrations (P =
      0.007). The mean DD +/- SD according to the SK concentrations of 5, 30, 50, and
      100 IU/mL was: 0.69 +/- 0.12, 0.78 +/- 0.14, 1.04 +/- 0.14 and 2.40 +/- 1.09  MU
      g/mL. There were no significant changes of clot weight at different SK
      concentrations. Gradual loss and increased branching of fibrin in both PPP and SK
      were observed. Quantitation of DD and morphology of fibrin loss as observed by
      the imaging features are in keeping with fibrinolytic activity. Combination of DD
      levels and confocal microscopic features was successfully applied to evaluate the
      in vitro WB clot lysis method described here. 

PMID- 24660001
TI  - Primary chest wall abscess mimicking a breast tumor that occurred after blunt
      chest trauma: a case report.
AB  - Primary chest wall abscess occurring after blunt chest trauma is rare. We present
      the case of a 50-year-old woman who presented with a swelling in her left breast.
      The patient had experienced blunt chest trauma 2 months back. Needle aspiration
      revealed pus formation in the patient's chest. Computed tomography revealed a
      mass in the lower region of the left mammary gland, with thickening of the
      parietal pleura and skin and fracture of the fifth rib under the abscess.
      Following antibiotic administration and irrigation of the affected region,
      surgical debridement was performed. During surgery, we found that the pectoralis
      major muscle at the level of the fifth rib was markedly damaged, although the
      necrotic tissue did not contact the mammary gland. We diagnosed the lesion as a
      chest wall abscess that occurred in response to blunt chest trauma. Her
      postoperative course was uneventful. There has been no recurrence for six months
      after surgery. 

PMID- 24660002
TI  - Malignant lymphoma in the parasellar region.
AB  - The entity of pituitary (sellar or parasellar) lymphoma includes primary
      pituitary lymphoma (PPL) and secondary pituitary lymphoma (SPL). The latter has
      an involvement of systemic lymphoma. Both of these lymphomas are extremely rare.
      We describe a patient with SPL showing a good prognosis. A 78-year-old woman
      presented with diplopia, left ptosis, and back pain. Magnetic resonance (MR)
      imaging revealed a parasellar mass lesion extending to the upper clivus and
      another mass lesion with compression fracture of the Th3 vertebral body.
      Transsphenoidal exploration was performed, and it showed diffuse large B-cell
      lymphoma. Based on the positive tumor cells in the following bone marrow
      aspiration and hepatosplenomegaly in computed tomography (CT) findings, this
      patient was diagnosed as having a pituitary involvement of systemic lymphoma.
      After chemotherapy, she achieved complete remission for 4 years. The entity of
      pituitary lymphoma is extremely rare. Nineteen cases of PPL and 16 cases of SPL
      have been reported. Generally, clinical and radiological diagnosis was difficult
      because there are no specific findings. Therefore, biopsy was necessary in all of
      the cases. T2 hypointensity of a lesion in MR imaging in addition to an elevated
      serum level of soluble interleukin-2 receptor (sIL-2R) in a patient with a sellar
      lesion can be useful clues for the differential diagnosis of this rare disease. 

PMID- 24660003
TI  - Scalp-ear-nipple syndrome: a case report.
AB  - The scalp-ear-nipple (SEN) syndrome is an infrequent congenital disease. Its main
      features are scalp defects, malformed ears, and absence of nipples. Most of the
      reported cases are autosomal dominant. We report on a patient suffering SEN
      syndrome with possible autosomal recessive inheritance. It is concluded that SEN
      syndrome should be recognized as an entity with genetic heterogeneity once there
      is evidence of different genetic manner of inheritance described in this disease.

PMID- 24660004
TI  - The elderly and the future of pharmacy / Les personnes agees et l'avenir de la
      pharmacie.

PMID- 24660005
TI  - Domperidone as an unintended antipsychotic.

PMID- 24660006
TI  - The Oz craze: The effect of pop culture media on health care.

PMID- 24660007
TI  - New year, new challenges.

PMID- 24660008
TI  - A case study in mobilizing all pharmacy team members in the community setting: A
      clinical facilitation role for pharmacy technicians.

PMID- 24660009
TI  - Managing chronic diseases in the frail elderly: More than just adhering to
      clinical guidelines.

PMID- 24660010
TI  - Practice guidelines for pharmacists: The pharmacological management of rheumatoid
      arthritis with traditional and biologic disease-modifying antirheumatic drugs.

PMID- 24660011
TI  - Educational needs, practice patterns and quality indicators to improve geriatric
      pharmacy care.
AB  - BACKGROUND: As the population ages and pressure increases to reduce adverse drug
      reactions and drug-related hospitalizations in the elderly, there will be a
      growing demand for pharmacists to competently take on shared responsibility for
      effective and safe prescribing in older adults. METHODS: A cross-sectional postal
      survey was distributed to 3927 hospital and community pharmacists across Quebec
      about their educational needs and practice patterns in geriatric care.
      Perceptions of different quality performance indicators were sought. Modifiable
      factors associated with higher performance were determined using univariate
      logistic regression. RESULTS: Seven hundred six pharmacists (18%) completed the
      survey. Less than 50% were aware of the prevalence of polypharmacy, inappropriate
      prescribing, drug-related hospitalizations or falls in the geriatric population.
      Forty-one percent of community pharmacists and 74% of hospital pharmacists
      acknowledged familiarity with the Beers criteria of drugs to avoid in the
      elderly. The likelihood of screening for inappropriate prescriptions was 2.96
      (95% confidence interval = 1.97-4.47) among pharmacists familiar with the Beers
      criteria and 2.24 (95% confidence interval = 1.50-3.34) among those who received
      continuing geriatric education in the workplace. On average, pharmacists reported
      having time to conduct detailed medication reviews in 30% of their older
      patients. The 2 quality indicators of geriatric care that were ranked most
      pertinent were being able to track the number of patients requiring
      hospitalization for drug-related problems and monitoring rates of inappropriate
      prescriptions. Ninety-six percent of respondents desired continuing education
      about geriatric care. CONCLUSION: Exposure to continuing education in geriatric
      pharmacotherapy in the workplace is the most consistent determinant of
      professional performance to improve drug outcomes in the elderly.

PMID- 24660012
TI  - Mixed messages: The Blueprint for Pharmacy and a communication gap.
AB  - BACKGROUND: More than 5 years ago, the Blueprint for Pharmacy developed a plan
      for transitioning pharmacy practice toward more patient-centred care. Much of the
      strategy for change involves communicating the new vision. OBJECTIVE: To evaluate
      the communication of the Vision for Pharmacy by the organizations and
      corporations that signed the Blueprint for Pharmacy's Commitment to Act. METHODS:
      The list of 88 signatories of the Commitment to Act was obtained from the
      Blueprint for Pharmacy document. The website of each of these signatories was
      searched for all references to the Blueprint for Pharmacy or Vision for Pharmacy.
      Each of the identified references was then analyzed using summative content
      analysis. RESULTS: A total of 934 references were identified from the webpages of
      the 88 signatories. Of these references, 549 were merely links to the Blueprint
      for Pharmacy's website, 350 of the references provided some detailed information
      about the Blueprint for Pharmacy and only 35 references provided any specific
      plans to transition pharmacy practice. CONCLUSION: Widespread proliferation of
      the Vision for Pharmacy has not been achieved. One possible explanation for this
      is that communication of the vision by the signatories has been incomplete. To
      ensure the success of future communications, change leaders must develop
      strategies that consider how individual pharmacists and pharmacies understand the
      message.

PMID- 24660014
TI  - Canadian pharmacists conference 2014.

PMID- 24660013
TI  - Increasing the safe and effective use of medications: The new federal priority.

PMID- 24660015
TI  - Effects of Selenium-Enriched Protein from Ganoderma lucidum on the Levels of IL-1
      beta and TNF- alpha , Oxidative Stress, and NF- kappa B Activation in Ovalbumin
      Induced Asthmatic Mice.
AB  - The purpose of this study was to compare the effect and toxicity of organic
      selenium (Pro-Se) with inorganic selenium (IOSe) in preventing asthma in
      ovalbumin-induced asthmatic mice. After the mice were treated orally with Pro-Se
      and IOSe, respectively, the plasma Se levels, Se accumulation in liver and
      kidney, tumor necrosis factor alpha (TNF- alpha ), interleukin 1 beta (IL-1 beta
      ), oxidative stress, and NF- kappa B activation in lung were examined. The
      results showed that the serumal Se levels in the mice fed the Pro-Se were
      significant (P < 0.01) elevations. It results in restoration of the level of
      endogenous antioxidant enzyme, lower levels of TNF- alpha and IL-1 beta , and
      activated NF- kappa B in the asthmatic mice. Our experiments have demonstrated
      profound differences between the activities of organic selenium and inorganic
      selenium in experimental conditions. These data provide an important proof of the
      concept that organic selenium might be a new potential therapy for the management
      of childhood asthma in humans. 

PMID- 24660016
TI  - Traditional chinese medicine syndromes for essential hypertension: a literature
      analysis of 13,272 patients.
AB  - Background. To simplify traditional Chinese medicine syndrome differentiation and
      allow researchers to master syndrome differentiation for hypertension, this paper
      retrospectively studied the literature and analyzed syndrome elements
      corresponding to hypertension syndromes. Methods. Six databases including PubMed,
      EMBASE, Chinese Bio-Medical Literature Database, Chinese National Knowledge
      Infrastructure, Chinese Scientific Journal Database, and Wan-fang Data were
      searched from 1/January/2003 to 30/October/2013. We included all clinical
      literature testing hypertension syndromes and retrospectively studied the
      hypertension literature published from 2003 to 2013. Descriptive statistics
      calculated frequencies and percentages. Results. 13,272 patients with essential
      hypertension were included. Clinical features of hypertension could be attributed
      to 11 kinds of syndrome factors. Among them, seven syndrome factors were excess,
      while four syndrome factors were deficient. Syndrome targets were mainly in the
      liver and related to the kidney and spleen. There were 33 combination syndromes.
      Frequency of single-factor syndromes was 31.77% and frequency of two-factor
      syndromes was 62.26%. Conclusions. Excess syndrome factors of hypertension
      patients include yang hyperactivity, blood stasis, phlegm turbidity, internal
      dampness, and internal fire. Deficient syndrome factors of hypertension patients
      are yin deficiency and yang deficiency. Yin deficiency with yang hyperactivity,
      phlegm-dampness retention, and deficiency of both yin and yang were the three
      most common syndromes in clinical combination. 

PMID- 24660017
TI  - Topical Antinociceptive Effect of Vanillosmopsis arborea Baker on Acute Corneal
      Pain in Mice.
AB  - This study aimed to assess the possible topical antinociceptive activity of
      Vanillosmopsis arborea Baker essential oil (EOVA) and to clarify the underlying
      mechanism, using the acute model of chemical (eye wiping) nociception in mice.
      EOVA (25 to 200 mg/kg; p.o. and topical) evidenced significant antinociception
      against chemogenic pain in the test model of formalin-induced neuroinflammatory
      pain. Local application of 5 M NaCl solution on the corneal surface of the eye
      produced a significant nociceptive behavior, characterized by eye wiping. The
      number of eye wipes was counted during the first 30 s. EOVA (25, 50, 100, and 200
      mg/kg; p.o. and topical) significantly decreased the number of eye wipes.
      Naloxone, yohimbine, L-NAME, theophylline, glibenclamide, and ruthenium red had
      no effect on the antinociceptive effect of EOVA. However, ondansetron, p
      chlorophenylalanine methyl ester (PCPA), capsazepine, prazosin, and atropine
      prevented the antinociception induced by EOVA. These results indicate the topical
      antinociceptive effect of EOVA and showed that 5-HT, alpha 1, TRPV1, and central
      muscarinic receptors might be involved in the antinociceptive effect of EOVA in
      the acute corneal model of pain in mice. 

PMID- 24660018
TI  - Influence of forest therapy on cardiovascular relaxation in young adults.
AB  - Background. Despite increasing attention toward forest therapy as an alternative
      medicine, very little evidence continues to be available on its therapeutic
      effects. Therefore, this study was focused on elucidating the health benefits of
      forest walking on cardiovascular reactivity. Methods. Within-group comparisons
      were used to examine the cardiovascular responses to walking in forest and urban
      environments. Forty-eight young adult males participated in the two-day field
      research. Changes in heart rate variability, heart rate, and blood pressure were
      measured to understand cardiovascular reactivity. Four different questionnaires
      were used to investigate the changes in psychological states after walking
      activities. Results. Forest walking significantly increased the values of ln(HF)
      and significantly decreased the values of ln(LF/HF) compared with the urban
      walking. Heart rate during forest walking was significantly lower than that in
      the control. Questionnaire results showed that negative mood states and anxiety
      levels decreased significantly by forest walking compared with urban walking.
      Conclusion. Walking in the forest environment may promote cardiovascular
      relaxation by facilitating the parasympathetic nervous system and by suppressing
      the sympathetic nervous system. In addition, forest therapy may be effective for
      reducing negative psychological symptoms. 

PMID- 24660019
TI  - Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses.
AB  - Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent
      infection, which in the absence of treatment leads to AIDS and death in almost
      all infected individuals. HIV infection elicits a vigorous immune response
      starting about 2-3 weeks post infection that can lower the amount of virus in the
      body, but which cannot eradicate the virus. How HIV establishes a chronic
      infection in the face of a strong immune response remains poorly understood. It
      has been shown that HIV is able to rapidly change its proteins via mutation to
      evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an
      HIV-infected patient will generate 4-12 CTL responses specific for parts of viral
      proteins called epitopes. Such CTL responses lead to strong selective pressure to
      change the viral sequences encoding these epitopes so as to avoid CTL
      recognition. Indeed, the viral population "escapes" from about half of the CTL
      responses by mutation in the first year. Here we review experimental data on HIV
      evolution in response to CTL pressure, mathematical models developed to explain
      this evolution, and highlight problems associated with the data and previous
      modeling efforts. We show that estimates of the strength of the epitope-specific
      CTL response depend on the method used to fit models to experimental data and on
      the assumptions made regarding how mutants are generated during infection. We
      illustrate that allowing CTL responses to decay over time may improve the fit to
      experimental data and provides higher estimates of the killing efficacy of HIV
      specific CTLs. We also propose a novel method for simultaneously estimating the
      killing efficacy of multiple CTL populations specific for different epitopes of
      HIV using stochastic simulations. Lastly, we show that current estimates of the
      efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by
      more frequent sampling of viral sequences and by combining data on sequence
      evolution with experimentally measured CTL dynamics.

PMID- 24660020
TI  - Fetal ECG extraction from abdominal signals: a review on suppression of
      fundamental power line interference component and its harmonics.
AB  - Interference of power line (PLI) (fundamental frequency and its harmonics) is
      usually present in biopotential measurements. Despite all countermeasures, the
      PLI still corrupts physiological signals, for example, electromyograms (EMG),
      electroencephalograms (EEG), and electrocardiograms (ECG). When analyzing the
      fetal ECG (fECG) recorded on the maternal abdomen, the PLI represents a
      particular strong noise component, being sometimes 10 times greater than the fECG
      signal, and thus impairing the extraction of any useful information regarding the
      fetal health state. Many signal processing methods for cancelling the PLI from
      biopotentials are available in the literature. In this review study, six
      different principles are analyzed and discussed, and their performance is
      evaluated on simulated data (three different scenarios), based on five
      quantitative performance indices. 

PMID- 24660021
TI  - The relationship between the 24 h blood pressure variability and carotid intima
      media thickness: a compared study.
AB  - Large blood pressure variability (BPV) will not only harm the target organ but
      also increase the possibility of the cardiovascular events. Since the damage of
      vascular system always leads to the alteration of the carotid wall, the structure
      and function of the carotid artery have been extensively examined in previous
      studies. In this work we conduct a study (60 subjects, aged 33-79) to evaluate
      the relationship between BPV and carotid intima-media thickness (IMT) in
      Shenzhen, which is one large city in the southern area of China. In our study,
      the blood pressure (BP) was collected using the 24 h ambulatory BP monitoring,
      and the BPV was evaluated using standard deviation (SD), coefficient of variation
      (CV), and average real variability (ARV) during 24 h, daytime and nighttime. All
      the IMT measurements are collected by ultrasound. The results show that both the
      daytime, and 24 h systolic BPV evaluated by three indices are positively
      associated with IMT. Among them, daytime systolic BPV evaluated with ARV is the
      best variable to represent the increasing of carotid IMT. In addition, after
      adjusting by age, sex, smoking, hypertension, and mean BP and PP values, 24 h
      diastolic BPV evaluated with SD also presents the favorable performance. 

PMID- 24660022
TI  - Pulse waveform classification using support vector machine with Gaussian time
      warp edit distance kernel.
AB  - Advances in signal processing techniques have provided effective tools for
      quantitative research in traditional Chinese pulse diagnosis. However, because of
      the inevitable intraclass variations of pulse patterns, the automatic
      classification of pulse waveforms has remained a difficult problem. Utilizing the
      new elastic metric, that is, time wrap edit distance (TWED), this paper proposes
      to address the problem under the support vector machines (SVM) framework by using
      the Gaussian TWED kernel function. The proposed method, SVM with GTWED kernel
      (GTWED-SVM), is evaluated on a dataset including 2470 pulse waveforms of five
      distinct patterns. The experimental results show that the proposed method
      achieves a lower average error rate than current pulse waveform classification
      methods. 

PMID- 24660023
TI  - Is Insecure Parent-Child Attachment a Risk Factor for the Development of Anxiety
      in Childhood or Adolescence?
AB  - In this article, we address how and why parent-child attachment is related to
      anxiety in children. Children who do not form secure attachments to caregivers
      risk developing anxiety or other internalizing problems. While meta-analyses
      yield different findings regarding which insecurely attached children are at
      greatest risk, our recent studies suggest that disorganized children may be most
      at risk. Insecure attachment itself may contribute to anxiety, but insecurely
      attached children also are more likely to have difficulties regulating emotions
      and interacting competently with peers, which may further contribute to anxiety.
      Clinical disorders occur primarily when insecure attachment combines with other
      risk factors. In this article, we present a model of factors related to
      developing anxiety.

PMID- 24660024
TI  - Effect of disease and recovery on functional anatomy in brain tumor patients:
      insights from functional MRI and diffusion tensor imaging.
AB  - Patients with brain tumors provide a unique opportunity to understand functional
      brain plasticity. Using advanced imaging techniques, such as functional MRI and
      diffusion tensor imaging, we have gained tremendous knowledge of brain tumor
      behavior, transformation, infiltration and destruction of nearby structures.
      Using these advanced techniques as an adjunct with more proven techniques, such
      as direct cortical stimulation, intraoperative navigation and advanced
      microsurgical techniques, we now are able to better formulate safer resection
      trajectories, perform larger resections at reduced risk and better counsel
      patients and their families about possible complications. Brain mapping in
      patients with brain tumors and other lesions has shown us that the old idea of
      fixed function of the adult cerebral cortex is not entirely true. Improving care
      for patients with brain lesions in the future will depend on better understanding
      of the functional organization and plasticity of the adult brain. Advanced
      noninvasive brain imaging will undoubtedly play a role in advancing this
      understanding.

PMID- 24660025
TI  - Tracking and treating activated T cells.
AB  - Upon activation, T cells of various subsets are the most important mediators in
      cell-mediated immune responses. Activated T cells play an important role in
      immune system related diseases such as chronic inflammatory diseases, viral
      infections, autoimmune disease, transplant rejection, Crohn disease, diabetes,
      and many more. Therefore, efforts have been made to both visualize and treat
      activated T cells specifically. This review summarizes imaging approaches and
      selective therapeutics for activated T cells and gives an outlook on how tracking
      and treating can be combined into theragnositc agents for activated T cells.

PMID- 24660026
TI  - Clinical application of expectorant therapy in chronic inflammatory airway
      diseases (Review).
AB  - Airway mucus hypersecretion is a significant clinical and pathological feature of
      chronic inflammatory airway diseases. Its clinical presentations include
      recurrent coughing and phlegm. Airway mucus is closely associated with the
      occurrence, development and prognosis of chronic inflammatory airway diseases and
      critically affects the lung function, quality of life, hospitalization rate and
      mortality of patients with chronic inflammatory airway diseases. Therefore,
      expectorant therapies targeting the potential mechanisms of mucus hypersecretion
      have been the focus of numerous studies. Conventional expectorants are mainly
      mucoactive medicines, including nausea-stimulating expectorants, mucolytics,
      mucokinetics, and proteases and nucleases. In addition, certain traditional
      Chinese herbal medicines and non-mucoactive agents, including muscarinic
      acetylcholine receptor antagonists, corticosteroids, leukotriene receptor
      antagonists and macrolide antibiotics, have also shown expectorant effects.
      Several novel medicines for expectorant therapy have emerged, including
      cholesterol-lowering statins, epidermal growth factor receptor tyrosine kinase
      inhibitors, phosphodiesterase-4 inhibitors, stanozolol, surfactants, flavonoids,
      tachykinin receptor antagonists, protease inhibitors, cytokine antagonists and
      purinergic agonists. With the increasing number of multidisciplinary studies, the
      effectiveness of expectorant therapy for the treatment of chronic inflammatory
      airway diseases has been confirmed. Therefore, the development of novel
      expectorants and the standardization of expectorant therapy are the direction and
      focus of future studies, thus benefiting patients who have a chronic inflammatory
      airway disease.

PMID- 24660027
TI  - Mechanism of blood-retinal barrier breakdown induced by HIV-1 (Review).
AB  - Human immunodeficiency virus (HIV)-1 has been detected in ocular tissues;
      however, the mechanism of entry has not been established. It has been
      hypothesized that the blood-retinal barrier (BRB), a critical guardian against
      microbial invasion of the eye, may be compromised in the presence of HIV-1 in the
      eye. In vivo and in vitro model systems have shown that the breach of tight
      junctions induced by HIV-1-associated factors contributes to the breakdown of the
      BRB. The present study reviews the mechanism of tight junction disruption,
      focusing on signaling pathways, the expression of enzymes, including
      metalloproteinases, and cytokines that affect inflammation. The studied pathways
      may be potential targets for the prevention of ocular HIV complications.

PMID- 24660028
TI  - Downregulation of L1CAM inhibits proliferation, invasion and arrests cell cycle
      progression in pancreatic cancer cells in vitro.
AB  - The aim of the present study was to establish the effect of silencing L1 cell
      adhesion molecule (L1CAM) on the proliferation, invasion, cell cycle progression
      and apoptosis of pancreatic cancer cells, and to determine the potential
      molecular mechanisms that are involved. The human Capan-2 pancreatic cancer cell
      line was infected with lentivirus-mediated short hairpin RNA (shRNA) to target
      L1CAM. Cell proliferation and invasion were analyzed using cell counting kit-8
      and Transwell assays, respectively, and cell cycle progression and apoptosis were
      analyzed using flow cytometry. L1CAM protein expression in Capan-2 cells
      decreased following shRNA-L1CAM infection. Furthermore, knockdown of L1CAM
      significantly inhibited cell proliferation and reduced the number of invasive
      cells, while increasing the percentage of cells in the G0/G1 phase (P<0.05).
      However, the effect on apoptosis was not identified to be statistically
      significant. In addition, L1CAM silencing may induce activation of
      p38/extracellular signal regulated kinase 1/2. Downregulation of L1CAM may
      inhibit proliferation, invasion and arrests cell cycle progression in pancreatic
      cancer via p38/ERK1/2 signal pathway, and therefore, L1CAM may serve as a
      potential target for gene therapy in pancreatic cancer.

PMID- 24660029
TI  - Instilled air promotes lipopolysaccharide-induced acute lung injury.
AB  - Optimization of intratracheal instillation is necessary to establish an ideal
      animal model of acute lung injury (ALI) in order to further reveal the cellular
      and molecular pathogenesis of ALI. It is possible that instilling air from a
      prefilled syringe may promote the delivery of reagents into the alveolar spaces,
      resulting in different pulmonary responses. In the present study, the influence
      of instilling air by trans-tracheal intratracheal instillation in a
      lipopolysaccharide (LPS)-induced mouse model of ALI was investigated. The
      bronchoalveolar lavage (BAL) fluid biochemical index, BAL fluid differential cell
      counts, lung wet/dry weight ratio, lung histology and BAL fluid interleukin-8 (IL
      8) levels were assessed 24 h subsequent to intratracheal instillation. Instilled
      air promoted LPS-induced ALI, as indicated by the severity of acute pulmonary
      inflammation and increased IL-8 release. In conclusion, this study indicates that
      instilled air may be used to improve the intratracheal instillation procedure and
      to establish a more reliable animal model of ALI.

PMID- 24660030
TI  - Protective effect of senegenin on splenectomy-induced postoperative cognitive
      dysfunction in elderly rats.
AB  - Postoperative cognitive dysfunction (POCD) is common in elderly patients.
      Senegenin, an active component of extracts from Polygala tenuifolia root, a
      traditional Chinese medicine, has neuroprotective and neuroregenerative effects.
      However, the mechanism underlying the effects of senegenin against postoperative
      cognitive impairment in elderly individuals has yet to be elucidated. The aim of
      this study was to investigate the protective effects of senegenin on the
      cognitive functions of elderly rats with splenectomy-induced POCD. Results from a
      Morris water maze test suggested that splenectomy induced a transient cognitive
      deficiency in the elderly rats; however, when the rats were treated with
      senegenin, the cognitive impairment was notably attenuated. Further experiments
      showed that senegenin significantly inhibited the mRNA and protein expression of
      several key pro-inflammatory cytokines, specifically, tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and IL-8, in the hippocampal
      tissues of elderly rats following splenectomy. In order to investigate the
      molecular mechanism involved, the expression and activity of the Toll-like
      receptor 4 (TLR4) signaling pathway was assessed. On day 1 postoperatively, it
      was observed that senegenin markedly suppressed the mRNA and protein expression
      of TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing
      adaptor-inducing interferon-beta (TRIF). Furthermore, the phosphorylation levels
      of nuclear factor-kappaB (NF-kappaB) p65 and inhibitor of NF-kappaB
      (IkappaBalpha) were also decreased following senegenin treatment on the first day
      subsequent to surgery. These results suggest that senegenin suppressed
      splenectomy-induced transient cognitive impairment in elderly rats, possibly by
      downregulating two signaling pathways involved in inflammation, TLR4/MyD88/NF
      kappaB and TLR4/TRIF/NF-kappaB, to further inhibit the expression of key pro
      inflammatory cytokines, specifically, TNF-alpha, IL-1beta, IL-6 and IL-8, and
      ultimately the neuroinflammation in the hippocampal tissues. In conclusion, the
      present study revealed that senegenin exhibited neuroprotective effects against
      splenectomy-induced transient cognitive impairment in elderly rats, which
      indicated that senegenin may be a promising agent for the treatment of POCD.

PMID- 24660031
TI  - CD154 blockade modulates the ratio of Treg to Th1 cells and prolongs the survival
      of allogeneic corneal grafts in mice.
AB  - Administration of anti-CD154 monoclonal antibody (mAb) may prolong the survival
      of an allograft; however, the associated therapeutic mechanisms remain poorly
      understood. This study aimed to evaluate the effects of anti-CD154 mAb on T-cell
      responses in a mouse model of corneal allograft transplantation. BALB/c mice were
      transplanted with corneal grafts from C57BL/6 mice and treated intraperitoneally
      with 250 MUg anti-CD154 mAb or isotype IgG on days 0, 3 and 6 post surgery. The
      transparency of the corneal grafts was evaluated for potential rejection signs by
      slit-lamp biomicroscopy and histopathology. The percentages of CD4+ T, Tim-3+CD4+
      T helper (Th) 1 and CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the spleen,
      ipsilateral draining lymph nodes and corneal grafts, and the frequency of splenic
      IFN-gamma+ and IL-10+ expression in CD4+ T cells were determined by flow
      cytometry. Moreover, the ratio of Tregs to Th1 cells was calculated and the
      suppressive activity of splenic Tregs was measured. Anti-CD154 neutralization
      significantly prolonged the survival of the corneal allograft (P=0.0012) and
      reduced the numbers of inflammatory infiltrates in the corneal graft. In the
      spleen and lymph nodes, anti-CD154 treatment reduced the frequency of CD4+ T
      cells, Tregs and particularly Th1 cells. In the corneal allografts, anti-CD154
      treatment downregulated graft-infiltrated CD4+ T cells and Th1 cells, but
      increased graft-infiltrated Tregs. Furthermore, anti-CD154 treatment increased
      the frequency of splenic IL-10+CD4+ T cells and decreased the concentration of
      splenic IFN-gamma+CD4+ T cells. As a result, the ratio of Tregs to Th1 cells in
      the anti-CD154-treated recipients increased. Anti-CD154 treatment did not enhance
      the suppressive activity of Tregs in the recipients. The results indicate that
      the therapeutic effects of anti-CD154 mAb on prolonging the survival of the
      corneal allograft may be associated with an increased ratio of Tregs to Th1 cells
      in mice.

PMID- 24660032
TI  - Effects of resveratrol on apoptosis in a rat model of vascular dementia.
AB  - Resveratrol is a natural polyphenol widely present in plants, particularly in the
      skin of red grapes and in wine. It possesses a wide range of biological effects
      and exhibits neuroprotective effects in numerous diseases. However, data
      evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In
      the present study, the permanent, bilateral common carotid artery occlusion rat
      model was used to study the effects of resveratrol on VaD. The Morris water maze
      was used to test the spatial learning and memory performance of the rats. The
      expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose)
      polymerase (PARP) in the hippocampus were measured. The results showed that
      resveratrol inhibited memory impairment in the VaD rat model, and attenuated the
      increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and
      the reductions in the expression levels of Bcl-2 that were induced by VaD. These
      results provide a novel insight into the neuroprotective effects of resveratrol
      and its possible therapeutic role in VaD.

PMID- 24660033
TI  - Type-I interferon secretion in the acute phase promotes Cryptococcus neoformans
      infection-induced Th17 cell polarization in vitro.
AB  - Cryptococcosis is a potentially fatal fungal disease commonly identified in
      patients with acquired immunodeficiency syndrome. Cryptococcus infection induces
      strong pro-inflammatory cytokine secretion, i.e. type-I interferon (IFN-I) via
      the Toll-like receptor signaling pathway. However, innate immune responses are
      insufficient in host defense against fungi infection and the clearance of
      Cryptococcus is dependent on the T helper (Th)17 cell-mediated mucosal immune
      response. In this study, IFN-I was identified as the early response cytokine to
      Cryptococcus neoformans infection via quantitative PCR (qPCR) and IFN-I was
      demonstrated to be crucial for interleukin (IL)-17A secretion in T cells, but not
      in innate immune cells. In addition, blockade of IFN-I reduced the protein
      expression levels of IL-22 and IL-23 in Th17 cells in vitro. These results
      suggest additional functions of IFN-I in immune regulation, which may be pivotal
      for the development of clinical immune therapy.

PMID- 24660034
TI  - Single-stage combined anterior retropharyngeal and posterior approach for the
      resection and reconstruction of C2 metastatic tumors: A case report.
AB  - This study reports the case of a 44-year-old male who had experienced severe neck
      pain for one month and was diagnosed with a metastatic tumor of the left C2
      vertebral body and the left transverse process. The tumor was distributed to
      layers A-D and sectors 3-7 according to the Weinstein-Boriani-Biagini
      classification, and was in Category IV according to the Harrington classification
      system. A conventional posterior cervical approach was used to resect the left
      transverse process and part of the tumor in a piecemeal fashion, and spinal
      instrumentation was also performed. Gelfoam and absorbable hemostatic gauze were
      placed ventrally to the left vertebral artery and the left C3 nerve root over the
      tumor bed to prevent their accidental injury in the subsequent anterior approach.
      A high anterior retropharyngeal approach was then used to resect the tumorous C2
      vertebral body by corpectomy and to perform anterior reconstruction. Six months
      after the surgery, the patient remained pain free. Therefore, C2 metastatic tumor
      resection and spinal reconstruction can be fulfilled by a single-stage combined
      high anterior retropharyngeal and posterior approach.

PMID- 24660035
TI  - Ectopic pancreas in the anterior mediastinum: A report of two cases and review of
      the literature.
AB  - Ectopia of the pancreatic tissue is a developmental anomaly found in ~2% of all
      autopsies, and 70~90% of these anomalies are located in the gastrointestinal
      tract. Mediastinal localization of an ectopic pancreas is extremely rare. Herein,
      we report two cases with mediastinal ectopic pancreas clarified by pathology and
      shown by thoracic contrast-enhanced computed tomography (CT) and magnetic
      resonance imaging (MRI). In addition, a brief review of the relevant literatures
      is presented. Although CT and MRI manifestations of this lesion are nonspecific,
      certain notable findings need to be focused on. When there is a mass in the
      anterior mediastinum with marked and heterogeneous enhancement, along with
      necrotic and liquefied non-enhanced areas in the center, ectopic pancreas should
      be considered and differentiated from other neoplasms in this region.

PMID- 24660036
TI  - Role of FDG-PET/CT for monitoring soft tissue tumors.
AB  - The aim of the current study was to evaluate the limitations of 2-deoxy-2-F18
      fluoro-D-glucose positron emission tomography combined with computed tomography
      (FDG-PET/CT) when monitoring soft tissue tumors. The diagnostic criteria of
      malignancy was defined as the tumor having a maximum standardized uptake value
      (SUVmax) >=2.0 and a maximum diameter >=5 cm as measured using FDG-PET/CT. One
      hundred-and-thirteen patients, that were either included in the criteria or not,
      were compared. In addition, the values of SUVmax of the primary tumor and relapse
      in 12 patients were evaluated. The Kaplan-Meier analysis demonstrated that
      patients with tumors measuring >=5 cm size and >=2.0 SUVmax were associated with
      a worse survival rate. Among the 12 patients with relapse, statistical
      significances were detected in the tumor diameters, however, not in the SUVmax
      values. Thus, the criteria identified patients that were associated with a poor
      prognosis, and the SUVmax of distant metastases and local recurrences were
      identified to be significantly affected by tumor size.

PMID- 24660037
TI  - Antitumor and immunomodulatory effects of low-dose 5-FU on hepatoma 22 tumor
      bearing mice.
AB  - Low-dose 5-fluorouracil (5-FU), a widely used chemotherapeutic, has been reported
      to have immunomodulatory effects. This study aimed to evaluate the optimal dose
      of 5-FU that produces antitumor and immunomodulatory effects. In a hepatoma 22
      tumor-bearing mouse model, 0, 10, 20 and 40 mg/kg 5-FU (i.p.) was administered
      for 10 days. Tumor weight and volume were measured, thymus index (TI) and spleen
      index (SI) were calculated, and the number of white blood cells (WBCs) and
      lymphocytes (LYs) were counted following treatment. The percentages of CD3+,
      CD4+, CD8+ and natural killer (NK) cells were measured by flow cytometry. In
      addition, the body weights of the mice were measured and the average diet
      consumption was calculated. Administration of 5-FU produced a potent antitumor
      effect in a dose-dependent manner (P<0.01). At 20 and 40 mg/kg, a significant
      reduction of body weight and food consumption was observed. TI and SI decreased
      in the 20- and 40-mg/kg groups (P<0.01) for 10 days. The number of WBCs
      significantly decreased in each group (P<0.01); however, the number of LYs only
      decreased in the 40-mg/kg group (P<0.01). Percentages of CD3+ and CD4+ cells were
      increased in the 10- and 20-mg/kg groups (P<0.01). Thus, 5-FU at 10 mg/kg
      inhibits tumor growth while maintaining the immune function of the mice. 5-FU may
      exert its antitumor effect at a low dose with low toxicity and stimulate the host
      immune system. Future clinical trials taking into account the immunostimulatory
      capacity of chemotherapeutic agents are desirable for certain patients.

PMID- 24660038
TI  - ABCB1 haplotypes are associated with P-gp activity and affect a major molecular
      response in chronic myeloid leukemia patients treated with a standard dose of
      imatinib.
AB  - Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid
      leukemia (CML) patients, some individuals develop resistance due to impaired
      bioavailability. It has been previously demonstrated that the haplotypes for ATP
      binding cassette subfamily B member 1 (ABCB1)with c.1236C>T, c.3435C>T and
      c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA
      and its activity. These modifications may affect efflux transporter activity and
      response to treatment with IM. The aim of the present study was to investigate
      the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma
      levels and IM response. In total, 28 chronic-phase CML patients treated with a
      standard dose of IM (400 mg/day) were studied. The patients were selected
      according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T
      polymorphisms, and were classified into two groups based on the presence of the
      mutated allele in each genotype for the three ABCB1 polymorphisms. In addition,
      expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and
      solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. The P-gp
      activity in the wild-type group was found to be higher than that in the mutated
      group (59.1 vs. 38.3%; P=0.001). Furthermore, the patients who did not achieve
      major molecular response (MMR) showed a higher rate of efflux mediated by P-gp
      when compared with individuals who achieved MMR (64.7 vs. 45.7%; P=0.001). All
      patients without MMR demonstrated effluxes of >60%. In addition, patients without
      MMR exhibited lower plasma concentrations of IM compared with those with MMR
      (0.51 vs. 1.42 MUg/ml; P=0.001). Higher levels of SLC22A1 mRNA were observed in
      patients who achieved MMR and complete molecular response (P<0.05). In
      conclusion, the ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes
      are associated with reduced P-gp activity and MMR in chronic-phase CML patients
      treated with a standard dose of IM.

PMID- 24660039
TI  - In Vitro Microvessel Growth and Remodeling within a Three-dimensional
      Microfluidic Environment.
AB  - This paper presents in vitro microvascular network formation within 3D gel
      scaffolds made from different concentrations of type-I collagen, fibrin, or a
      mixture of collagen and fibrin, using a simple microfluidic platform. Initially,
      microvascular network formation of human umbilical vein endothelial cells was
      examined using live time-lapse confocal microscopy every 90 min from 3 h to 12 h
      after seeding within three different concentrations of collagen gel scaffolds.
      Among the three conditions of collagen gel scaffolds (2.0 mg/ml, 2.5 mg/ml, and
      3.0 mg/ml), the number of skeleton within collagen gel scaffolds was consistently
      the highest (3.0 mg/ml), followed by those of collagen gel scaffolds (2.5 mg/ml
      and 2.0 mg/ml). Results demonstrated that concentration of collagen gel
      scaffolds, which influences matrix stiffness and ligand density, may affect
      microvascular network formation during the early stages of vasculogenesis. In
      addition, the maturation of microvascular networks in monoculture under different
      gel compositions within gel scaffolds (2.5 mg/ml) was examined for 7 d using live
      confocal microscopy. It was confirmed that pure fibrin gel scaffolds are
      preferable to collagen gel or collagen/fibrin combinations, significantly
      reducing matrix retractions during maturation of microvascular networks for 7 d.
      Finally, early steps in the maturation process of microvascular networks for 14 d
      were characterized by demonstrating sequential steps of branching, expanding,
      remodeling, pruning, and clear delineation of lumens within fibrin gel scaffolds.
      Our findings demonstrate an in vitro model for generating mature microvascular
      networks within 3D microfluidic fibrin gel scaffolds (2.5 mg/ml), and furthermore
      suggest the importance of gel concentration and composition in promoting the
      maturation of microvascular networks.

PMID- 24660040
TI  - The Recovery Process of Postpartum Psychosis from Both the Woman's and Next of
      Kin's Perspective - An Interview Study in Sweden.
AB  - OBJECTIVES: The most serious type of psychiatric disorder in connection with
      childbirth is postpartum psychosis. With this disorder occasionally follows
      emotional rejection of the infant which has serious long term effect on mother
      and child. The aim of this study was to explore the experiences of the recovery
      process of postpartum psychosis from the women, from the partners of the women,
      and their next of kin. METHODS: Interviews were conducted with seven women, who
      had previously suffered postpartum psychosis, and six of their next of kin. The
      interviews were transcribed verbatim and analysed using content analysis.
      RESULTS: TWO CATEGORIES EMERGED: the recovery process and the circumstances of
      the support provided. The women and their next of kin spoke about the turning
      point in the illness, their own personal as well as their social recovery, the
      importance of support not only from relatives and friends, but also from
      professionals, and the use of medication. However, the key to recovery was an
      internal decision by the women themselves. CONCLUSION: Conclusion is that the
      recovery from this severe mental disorder requires hard work and the key to their
      recovery was the decision made by the women. This disorder causes a mental
      darkness to descend, but at the start of the recovery a dim light shines in the
      dark tunnel. The nursing staff must be made aware that good sleep is important
      for the psychiatric treatment and that recovery may take a long time. The nurse
      needs to provide hope and encouragement, as well as help the woman to recognise
      the strength that exists within her. To reduce the risk of a recurrence of the
      disorder, the staff needs to offer follow up visits.

PMID- 24660041
TI  - Health Problems and APN Interventions in Pregnant Women with Diabetes.
AB  - The purpose of this study was to compare health problems and advanced practice
      nursing (APN) interventions in two types of APN care provided to 41 childbearing
      women with diabetes. The study's design involved content analysis of interaction
      logs containing the process of APN care during two clinical trials: 1) APN care
      was added to physician care (n = 22); and, 2) half of physician care was
      substituted with APN care (n = 19). Women's' health problems and APN
      interventions were classified using the Omaha System's Problem Scheme and
      Intervention Scheme. The women, in the study, had a mean age of 30, and were
      predominantly Black, high school graduates, with a low income. The findings
      identified 61,004 health problems and 60,980 APN interventions from the
      interaction logs. APNs provided significantly more interventions antenatally to
      the women in the substitution group than to those in the additive group. However,
      the overall categories of problems were the same in both groups. Surveillance and
      health teaching/counseling were the top APN interventions antenatally and
      postpartum. Case management interventions were third most common for both groups,
      while treatments and procedures constituted the least number of APN interventions
      in each group before and after birth. When APNs shared care more equally with
      physicians, they intervened differently in type and number of interventions.
      Their broad range of skills and depth of understanding in clinical practice,
      health systems, family and personal issues allowed them to intervene early and
      effectively.

PMID- 24660042
TI  - Predictors of HIV Sexual Risk Behavior among Men Who Have Sex with Men, Men Who
      Have Sex with Men and Women, and Transgender Women.
AB  - Men who have sex with men, men who have sex with men and women, and transgender
      women are at high risk for HIV infection. This study seeks to clarify which known
      HIV risk factors (partner type, sex location, serodiscordance, multiple sex
      partners, substance use during sex) contribute to engagement in high-risk
      (unprotected receptive anal) sex in each population. Data collected from June
      2005 through June 2008 indicate all three populations display different HIV
      sexual risk profiles. The data suggest that HIV-prevention interventions should
      be individually tailored to address the specific needs of these three highly
      vulnerable and impacted populations.

PMID- 24660043
TI  - Using microfluidic chip to form brain-derived neurotrophic factor concentration
      gradient for studying neuron axon guidance.
AB  - Molecular gradients play a significant role in regulating biological and
      pathological processes. Although conventional gradient-generators have been used
      for studying chemotaxis and axon guidance, there are still many limitations,
      including the inability to maintain stable tempo-spatial gradients and the lack
      of the cell monitoring in a real-time manner. To overcome these shortcomings,
      microfluidic devices have been developed. In this study, we developed a
      microfluidic gradient device for regulating neuron axon guidance. A microfluidic
      device enables the generation of Brain-derived neurotrophic factor (BDNF)
      gradient profiles in a temporal and spatial manner. We test the effect of the
      gradient profiles on axon guidance, in the BDNF concentration gradient axon
      towards the high concentration gradient. This microfluidic gradient device could
      be used as a powerful tool for cell biology research. 

PMID- 24660044
TI  - Does Muller Cell Differentiation Occur Prior to the Emergence of Synapses in
      Embryonic Turtle Retina?
AB  - Muller cells are the main glial cells in the retina, and are related to plexiform
      layer activity. Recent studies have demonstrated that Muller cells are involved
      in the synaptic conservation, plasticity, development and metabolism of
      glutamate. During turtle retinal development, layers, cells and synapses appear
      at different times. The aim of this research is to study the emergence of Muller
      cells during embryonic development and their relationship with the
      synaptogenesis. The authors used retinas from Trachemys scripta elegans embryos
      at stages S14, 18, 20, 23, and 26. Some retinas were processed with
      immunocytochemistry in order to detect the presence of glutamine synthetase in
      Muller cells, which was used as a marker of these cells. Other retinas from the
      same stages were processed for ultrastructural studies. Samples were observed in
      confocal and transmission electron microscopes, respectively. The present results
      show that glutamine synthetase expression in Muller cells occurs at S18, before
      the emergence of the retinal layers and the early synapses.

PMID- 24660045
TI  - Macrophage Cryptococcus interactions: an update.
AB  - Cryptococcus species are fungal pathogens that are a leading cause of mortality.
      Initial inoculation is through the pulmonary route and, if disseminated, results
      in severe invasive infection including meningoencephalitis. Macrophages are the
      dominant phagocytic cell that interacts with Cryptococcus. Emerging theories
      suggest that Cryptococcus microevolution in macrophages is linked to survival and
      virulence within the host. In addition, Cryptococcus elaborates virulence factors
      as well as usurps host machinery to establish macrophage activation states that
      are permissive to intracellular survival and replication. In this review, we
      provide an update of the recent findings pertaining to macrophage interaction
      with Cryptococcus and focus on new avenues for biomedical research.

PMID- 24660046
TI  - Statistical Inference of Biometrical Genetic Model With Cultural Transmission.
AB  - Twin and family studies establish the foundation for studying the genetic,
      environmental and cultural transmission effects for phenotypes. In this work, we
      make use of the well established statistical methods and theory for mixed models
      to assess cultural transmission in twin and family studies. Specifically, we
      address two critical yet poorly understood issues: the model identifiability in
      assessing cultural transmission for twin and family data and the biases in the
      estimates when sub-models are used. We apply our models and theory to two real
      data sets. A simulation is conducted to verify the bias in the estimates of
      genetic effects when the working model is a sub-model.

PMID- 24660047
TI  - Pragmatic Language in autism and fragile X syndrome: Genetic and clinical
      applications.
AB  - Evidence suggests a strong genetic basis to autism. Our research program focuses
      on identifying genetically meaningful phenotypes in autism, through family
      genetic and cross-population methods, with a particular focus on language and
      social phenotypes that have been shown to aggregate in families of individuals
      with autism. In this article, we discuss recent findings from family study
      research implicating particular language and personality features as markers for
      genetic liability to autism and fragile X syndrome and FMR1-related variation in
      relatives. We conclude with consideration of the clinical implications of such
      findings.

PMID- 24660048
TI  - Trauma Exposure and Posttraumatic Symptoms in Hawaii: Gender, Ethnicity, and
      Social Context.
AB  - Eight-hundred thirty-three members of an ethnically diverse longitudinal cohort
      study in Hawaii were surveyed about their personal exposure to several types of
      traumatic events, socioeconomic resources, and mental health symptoms. Results
      replicated findings from prior research that while men and women are exposed to
      similar rates of trauma overall, women report more exposure to traumas high in
      betrayal (HB), while men report exposure to more traumas lower in betrayal (LB).
      Trauma exposure was predictive of mental health symptoms, with neglect, household
      dysfunction, and HB traumas predicting symptoms of depression, anxiety, PTSD,
      dissociation, and sleep disturbance, and LB traumas predicting PTSD and
      dissociation symptoms. Native Hawaiian ethnicity and poorer socioeconomic status
      were predictive of greater trauma exposure and symptoms. Results suggest that
      more inclusive definitions of trauma are important for gender equity, and that
      ethnic group variation in symptoms is better explained by factors such as
      differential trauma exposure and economic and social status differences, rather
      than minority status per se.

PMID- 24660049
TI  - Statistical approaches to analyzing HIV-1 neutralizing antibody assay data.
AB  - Neutralizing antibody assays are widely used in research toward development of a
      preventive HIV-1 vaccine. Currently, the neutralization potency of an antibody is
      typically quantified by the inhibitory concentration (IC) values (e.g., IC50),
      and the neutralization breadth is estimated by the empirical method. In this
      paper, we propose the AUC and pAUC measures for summarizing the titration curve,
      which complement the commonly used IC measure. We present multiple advantages of
      AUC over IC50, which include no complications due to censoring, the capability to
      explore low-level neutralization, and improved coverage probabilities and
      efficiency of estimators. We also propose statistical methods for determining
      positive neutralization and for estimating the neutralization breadth. The
      simulation results suggest that the AUC measure is preferable in particular as
      IC50s get closer to the highest concentration of antibodies tested. For the
      majority of the assay data, the AUC method is more powerful than the IC50 method.
      However, since these methods test different hypotheses, it is not unexpected that
      some virus-antibody combinations are AUC positive but IC50 negative or vice
      versa.

PMID- 24660050
TI  - Empirical Likelihood Approaches to Two-Group Comparisons of Upper Quantiles
      Applied to Biomedical Data.
AB  - In many biomedical studies, a difference in upper quantiles is of specific
      interest since the upper quantile represents the upper range of biomarkers and/or
      is used as the cut-off value for a disease classification. In this article, we
      investigate two-group comparisons of an upper quantile based on the empirical
      likelihood methodology. Two approaches, the classical empirical likelihood and
      'plug-in' empirical likelihood are used to construct the test statistics and
      their properties are theoretically investigated. Although the plug-in method is
      developed by the frame work of the empirical likelihood, the test statistic is
      not based on the maximization of the empirical likelihood, and is simplified by
      using indicator function in its construction, making it a unique test to
      investigate. Extensive simulation results demonstrate that the 'plug-in'
      empirical likelihood approach performs better to compare upper quantiles across
      various underlying distributions and sample sizes. For the actual application, we
      employ the developed methods to test the differences in upper quantiles in two
      different studies, the oral colonization of pneumonia pathogens for intensive
      care unit patients treated by two different oral treatments, and the biomarker
      expressions of normal and abnormal bronchial epithelial cells.

PMID- 24660052
TI  - Scaling and Exponent Equalities in Island Nucleation: Novel Results and
      Application to Organic Films.
AB  - It is known in thin-film deposition that the density of nucleated clusters N
      varies with the deposition rate F as a power law, N ~ Falpha. The exponent alpha
      is a function of the critical nucleus size i in a way that changes with the
      aggregation limiting process. We extend here the derivation of the analytical
      capture-zone distribution function Pbeta(s) = abeta .sbeta .exp(-bbetas2) of
      Pimpinelli and Einstein to generic aggregation-limiting processes. We show that
      the parameter beta is generally related to the critical nucleus size i and to the
      exponent alpha by the equality alpha.beta = i, in the case of compact islands.
      This remarkable result allows one to measure i with no a priori knowledge of the
      actual aggregation mechanism. We apply this equality to measuring the critical
      nucleus size for pentacene deposition on mica. This system shows a crossover from
      diffusion-limited to attachment-limited aggregation with increasing deposition
      rates.

PMID- 24660051
TI  - An Accessible Chiral Linker to Enhance Potency and Selectivity of Neuronal Nitric
      Oxide Synthase Inhibitors.
AB  - The three important mammalian isozymes of nitric oxide synthase (NOS) are
      neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Inhibitors
      of nNOS show promise as treatments for neurodegenerative diseases. Eight easily
      synthesized compounds containing either one (20a,b) or two (9a-d; 15a,b) 2-amino
      4-methylpyridine groups with a chiral pyrrolidine linker were designed as
      selective nNOS inhibitors. Inhibitor 9c is the best of these compounds, having a
      potency of 9.7 nM and dual selectivity of 693 and 295 against eNOS and iNOS,
      respectively. Crystal structures of nNOS complexed with either 9a or 9c show a
      double-headed binding mode, where each 2-aminopyridine head group interacts with
      either a nNOS active site Glu residue or a heme propionate. In addition, the
      pyrrolidine nitrogen of 9c contributes additional hydrogen bonds to the heme
      propionate, resulting in a unique binding orientation. In contrast, the lack of
      hydrogen bonds from the pyrrolidine of 9a to the heme propionate allows the
      inhibitor to adopt two different binding orientations. Both 9a and 9c bind to
      eNOS in a single-headed mode, which is the structural basis for the isozyme
      selectivity.

PMID- 24660053
TI  - "Vulnerability, Resiliency, and Adaptation: The Health of Latin Americans during
      the Migration Process to the United States"
AB  - In this paper, we offer a general outlook of the health of Latin Americans (with
      a special emphasis on Mexicans) during the different stages of the migration
      process to the U.S. given the usefulness of the social vulnerability concept and
      given that said vulnerability varies conspicuously across the different stages of
      the migration process. Severe migrant vulnerability during the transit and
      crossing has serious negative health consequences. Yet, upon their arrival to the
      U.S., migrant health is favorable in outcomes such as mortality by many causes of
      death and in several chronic conditions and risk factors, though these apparent
      advantages seem to disappear during the process of adaptation to the host
      society. We discuss potential explanations for the initial health advantage and
      the sources of vulnerability that explain its erosion, with special emphasis in
      systematic timely access to health care. Given that migration can affect social
      vulnerability processes in sending areas, we discuss the potential health
      consequences for these places and conclude by considering the immigration and
      health policy implications of these issues for the United States and sending
      countries, with emphasis on Mexico.

PMID- 24660054
TI  - Acute kidney injury is independently associated with death in patients with
      cirrhosis.
AB  - BACKGROUND AND AIMS: Current creatine-based criteria for defining acute kidney
      injury (AKI) are validated in general hospitalised patients but their application
      to cirrhotics (who are younger and have reduced muscle mass) is less certain. We
      aimed to evaluate current definitions of AKI (acute kidney injury network (AKIN)
      criteria) in a population of cirrhotic patients and correlate this with outcomes.
      METHODS: We prospectively identified patients with AKI and clinical, radiological
      or histological evidence of cirrhosis. We compared them with a control group with
      evidence of cirrhosis and no AKI. RESULTS: 162 cirrhotic patients were studied
      with a mean age of 56.8+/-14 years. They were predominantly male (65.4%) with
      alcoholic liver disease (78.4%). 110 patients had AKI: 44 stage 1, 32 stage 2 and
      34 stage 3. They were well matched in age, sex and liver disease severity with 52
      cirrhotics without AKI. AKI was associated with increased mortality (31.8% vs
      3.8%, p<0.001). Mortality increased with each AKI stage; 3.8% in cirrhotics
      without AKI, 13.5% stage 1, 37.8% stage 2 and 43.2% stage 3 (p<0.001 for trend).
      Worsening liver disease (Child-Pugh class) correlated with increased mortality:
      3.1% class A, 23.6% class B and 32.8% class C (p=0.006 for trend). AKI was
      associated with increased length of stay: median 6.0 days (IQR 4.0-8.75) versus
      16.0 days (IQR 6.0-27.5), p<0.001. Multivariate analysis identified AKI and Child
      Pugh classes B and C as independent factors associated with mortality.
      CONCLUSIONS: The utility of AKIN criteria is maintained in cirrhotic patients.
      Decompensated liver disease and AKI appear to be independent variables predicting
      death in cirrhotics.

PMID- 24660055
TI  - An Ultra-Stable Oxoiron(IV) Complex and Its Blue Conjugate Base.
AB  - Treatment of [FeII(L)](OTf)2 (4), (where L = 1,4,8-Me3cyclam-11-CH2C(O)NMe2) with
      iodosylbenzene yielded the corresponding S = 1 oxoiron(IV) complex
      [FeIV(O(L)](OTf)2 (5) in nearly quantitative yield. The remarkably high stability
      of 5 (t1/2 ~ 5 days at 25  degrees C) facilitated its characterization by X-ray
      crystallography and a raft of spectroscopic techniques. Treatment of 5 with
      strong base was found to generate a distinct, significantly less stable S = 1
      oxoiron(IV) complex, 6 (t1/2 ~ 1.5 hrs. at 0  degrees C), which could be
      converted back to 5 by addition of a strong acid; these observations indicate
      that 5 and 6 represent a conjugate acid-base pair. That 6 can be formulated as
      [FeIV(O)(L-H)](OTf) was further supported by ESI mass spectrometry, spectroscopic
      and electrochemical studies, and DFT calculations. The close structural
      similarity of 5 and 6 provided a unique opportunity to probe the influence of the
      donor trans to the FeIV=O unit upon its reactivity in H-atom transfer (HAT) and O
      atom transfer (OAT), and 5 was found to display greater reactivity than 6 in both
      OAT and HAT. While the greater OAT reactivity of 5 is expected on the basis of
      its higher redox potential, its higher HAT reactivity does not follow the anti
      electrophilic trend reported for a series of [FeIV(O)(TMC)(X)] complexes (TMC =
      tetramethylcyclam) and thus appears to be inconsistent with the Two-State
      Reactivity rationale that is the prevailing explanation for the relative facility
      of oxoiron(IV) complexes to undergo HAT.

PMID- 24660056
TI  - Transformations of X (C, O, N)-CN Bonds: Cases of Selective X (C, O, N)-C
      Activation.
AB  - Activation of C-C, C-N, and C-O bonds has in recent decades been recognized as a
      valuable strategic objective. While considerable progress has been achieved, many
      of the more challenging issues, e.g., regioselective activation of specific C-X
      (C, O, N) bonds, chemoselective cleavage of C(sp3)-X bonds, enantioselective
      activation and even the successful application of solid catalysts in such
      transformations remain elusive. The research disclosed herein summarize recent
      advances in C-X bond cleavages, including regioselective processes, although the
      carbon is activated in the form of a cyano group.

PMID- 24660057
TI  - Osteogenic differentiation of human mesenchymal stem cells on alpha5 integrin
      binding peptide hydrogels is dependent on substrate elasticity.
AB  - The extracellular matrix plays a crucial role in controlling human mesenchymal
      stem cell (hMSC) biology including differentiation, and alpha5beta1 integrin
      signaling plays an important role during osteogenic differentiation of hMSCs.
      Here, peptide-functionalized hydrogels were used to examine the role of
      alpha5beta1 integrin signaling in inducing osteogenic differentiation in hMSCs.
      Further, the role of substrate elasticity was also studied. A thiolene chemistry
      was used to functionalize poly(ethylene glycol) hydrogels with a pendant peptide
      moieity, c(RRETAWA), as previous studies have shown that RRETAWA containing
      peptides bind to the alpha5beta1 integrin with very high specificity. Notably,
      hMSC attachment to c(RRETAWA)-functionalized hydrogels was found to occur
      primarily through alpha5 integrins, as the number of attached cells was
      significantly reduced to ~20% upon blocking the alpha5 integrin during culture.
      To investigate the interplay between stiffness and c(RRETAWA) concentration,
      hydrogels were formulated with Young's moduli of ~2 kPa (soft) and ~25 kPa
      (stiff) and c(RRETAWA) concentrations of 0.1 mM and 1 mM. Stiff substrates led to
      ~3.5 fold higher hMSC attachment and ~3 fold higher cell area in comparison to
      soft substrates. hMSCs formed robust and larger focal adhesions on stiff
      substrates at 1 mM c(RRETAWA) compared to soft substrates. Alkaline phosphatase
      (ALP) activity in hMSCs cultured on stiff gels at 0.1 mM and 1 mM c(RRETAWA) was
      increased 2.5 and 3.5 fold, respectively after 14 days in growth media. hMSCs did
      not show an increase in ALP activity when cultured on soft gels. Further, gene
      expression of osteogenic related genes, core binding factor-1, osteopontin and
      Collagen-1a at day 14 in hMSCs cultured on stiff gels at 1 mM c(RRETAWA) were
      increased 10, 7 and 4 fold, respectively, while on soft gels, gene expression was
      at basal levels. Collectively, these results demonstrate that the combination of
      high substrate stiffness and alpha5beta1 integrin signaling stimulated by
      c(RRETAWA) is sufficient to induce osteogenic differentiation of hMSCs without
      requiring the addition of soluble factors.

PMID- 24660058
TI  - Lauryl-poly-L-lysine: A New Antimicrobial Agent?
AB  - The development of multiple antibiotic resistance is a global problem. It is
      necessary to find new tools whose mechanisms of action differ from those of
      currently used antibiotics. It is known that fatty acids and cationic
      polypeptides are able to fight bacteria. Here, we describe the synthesis of fatty
      acids linked to a polypeptide with antibacterial activity. The linkage of fatty
      acids to a polypeptide is reported to increase the antibacterial effect of the
      linked fatty acid in comparison with free fatty acids (FA) or free poly-L-lysine
      (PLL) or a mixture of both (FA free + PLL free). A number of C6-C18 fatty acids
      were linked to PLL to obtain new synthetic products. These compounds were
      assessed in vitro to evaluate their antibacterial activity. Some fatty acid-PLLs
      showed a good ability to fight bacteria. Their bactericidal activity was
      evaluated, and, lauryl linked to PLL was found to be the most active product
      against both Gram-positive and Gram-negative bacteria. This new active component
      showed a good degree of specificity and reproducibility and its minimum
      inhibitory concentration (MIC) was comparatively good. The antibacterial activity
      of the lauryl-PLL compound suggests that it is a new and promising antimicrobial
      agent. 

PMID- 24660059
TI  - Immune activation and inflammation in patients with cardiovascular disease are
      associated with higher phenylalanine to tyrosine ratios: the ludwigshafen risk
      and cardiovascular health study.
AB  - Higher serum neopterin is associated with increased mortality in patients with
      coronary artery disease (CAD). Preferentially Th1-type cytokine interferon- gamma
      stimulates neopterin production by GTP cychlohydrolase I (GCH-I) in parallel in
      monocyte-derived macrophages and dendritic cells. In other cells, activation of
      GCH-I leads to the formation of 5,6,7,8-tetrahydrobiopterin (BH4), the necessary
      cofactor of amino acid hydroxylases like phenylalanine 4-hydroxylase (PAH). Serum
      concentrations of phenylalanine, tyrosine, neopterin, and high sensitivity C
      reactive protein (hsCRP) were measured in 1196 patients derived from the
      LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among
      patients referred for coronary angiography. The phenylalanine to tyrosine ratio
      (Phe/Tyr) served as an estimate of phenylalanine hydroxylase (PAH) enzyme
      activity. Serum concentrations of phenylalanine and tyrosine and of Phe/Tyr did
      not differ between individuals with or without CAD (Welch's t-test: P = n.s.).
      Higher neopterin and hsCRP concentrations were observed in CAD patients compared
      to controls (P < 0.0001) and they correlated with Phe/Tyr (Spearman's rank
      correlation for neopterin: r s = 0.216 and hsCRP: r s = 0.122; both of P <
      0.0001) concentrations. In conclusion, immune activation is associated with
      higher Phe/Tyr in CAD patients. Data indicates subnormal PAH activity which might
      be involved in the precipitation of neuropsychiatric symptoms in patients. 

PMID- 24660060
TI  - Etiology and Outcomes of ARDS in a Rural-Urban Fringe Hospital of South India.
AB  - Objectives. Etiology and outcomes of acute lung injury in tropical countries may
      be different from those of western nations. We describe the etiology and outcomes
      of illnesses causing acute lung injury in a rural populace. Study Design. A
      prospective observational study. Setting. Medical ICU of a teaching hospital in a
      rural-urban fringe location. Patients. Patients >=13 years, admitted between
      December 2011 and May 2013, satisfying AECC criteria for ALI/ARDS. Results. Study
      had 61 patients; 46 had acute lung injury at admission. Scrub typhus was the
      commonest cause (7/61) and tropical infections contributed to 26% of total cases.
      Increasing ARDS severity was associated with older age, higher FiO2 and
      APACHE/SOFA scores, and longer duration of ventilation. Nonsurvivors were
      generally older, had shorter duration of illness, a nontropical infection, and
      higher total WBC counts, required longer duration of ventilation, and had other
      organ dysfunction and higher mean APACHE scores. The mortality rate of ARDS was
      36.6% (22/61) in our study. Conclusion. Tropical infections form a major
      etiological component of acute lung injury in a developing country like India.
      Etiology and outcomes of ARDS may vary depending upon the geographic location and
      seasonal illnesses. 

PMID- 24660061
TI  - The syndrome of absence status epilepsy: review of the literature.
AB  - The authors review the literature for cases fulfilling the criteria for the
      proposed idiopathic generalized epilepsy syndrome (IGE) of absence status
      epilepsy described by Genton et al. (2008). Difficulties arising in diagnosing
      such cases are remarked, and possible overlapping with other proposed IGE
      syndromes is discussed. 

PMID- 24660062
TI  - Performance of Tuberculin Skin Test Measured against Interferon Gamma Release
      Assay as Reference Standard in Children.
AB  - Objectives. International guidelines differ in the threshold of tuberculin skin
      test (TST) induration regarded as indicating Mycobacterium (M.) tuberculosis
      infection. Interferon gamma release assay (IGRA) results were used as reference
      to assess performance of TST induration thresholds for detection of M.
      tuberculosis infection in children. Design. Systematic review which included
      studies containing data on TST, IGRA, and Bacillus Calmette-Guerin (BCG) status
      in children. Data bases searched were PubMed, EMBASE, and the Cochrane library.
      Specificities and sensitivities were calculated for TST thresholds 5, 10, and 15
      mm and correlated with age and geographical latitude. Results. Eleven studies
      with 2796 children were included. For BCG immunised children diameters of 5, 10,
      and 15 mm had median sensitivities of 87, 70, and 75% and specificities of 67,
      93, and 90%, respectively. In non-BCG immunised children median sensitivities
      were 94, 95, and 83% and specificities 91, 95, and 97%. At the 10 mm threshold
      age correlated negatively with sensitivity of TST (r = -0.65, P = 0.04) and
      latitude correlated positively (r = 0.71, P = 0.02). Conclusions. For the 10 mm
      threshold the sensitivity of the TST is lower in BCG immunised children. Younger
      age and higher geographical latitude were associated with higher sensitivity of
      the TST. 

PMID- 24660063
TI  - Boarding injuries: the long and the short of it.
AB  - As the popularity of longboarding increases, trauma centers are treating an
      increased number of high severity injuries. Current literature lacks descriptions
      of the types of injuries experienced by longboarders, a distinct subset of the
      skateboarding culture. A retrospective review of longboarding and skateboarding
      injury cases was conducted at a level II trauma center from January 1, 2006,
      through December 31, 2011. Specific injuries in addition to high injury severity
      factors (hospital and intensive care unit (ICU) length of stay (LOS), Injury
      Severity Score (ISS), patient treatment options, disposition, and outcome) were
      calculated to compare longboarder to skateboarder injuries. A total of 824
      patients met the inclusion criteria. Skull fractures, traumatic brain injuries
      (TBI), and intracranial hemorrhage (ICH) were significantly more common among
      longboard patients than skateboarders (P < 0.0001). All patients with an ISS
      above 15 were longboarders. Hospital and ICU LOS in days was also significantly
      greater for longboarders compared with skateboarders (P < 0.0001). Of the three
      patients that died, each was a longboarder and each experienced a head injury.
      Longboard injuries account for a higher incidence rate of severe head injuries
      compared to skateboard injuries. Our data show that further, prospective
      investigation into the longboarding population demographics and injury patterns
      is necessary to contribute to effective injury prevention in this population. 

PMID- 24660064
TI  - Sun-tanning perceptions of a new zealand urban population (1994-2005/6).
AB  - Background. Sun-tanning perceptions are monitored to identify changes and help
      refine targeting of skin cancer prevention messages. Aim. To investigate
      associations between perceptions of sun-tanning and demographic factors among a
      New Zealand urban population, 1994-2006. Methods. A telephone survey series was
      conducted during summer in 1994, 1997, 1999/2000, 2002/2003, and 2005/2006.
      Demographic and personal information (sex, age group, skin sun-sensitivity, and
      self-defined ethnicity) obtained from 6,195 respondents, 50.2% female, 15-69
      years, was investigated in relation to six sun-tanning related statements. A
      total "positive perceptions of tanning" (ProTan) score was also calculated.
      Regression analyses modelled each component and the ProTan score against survey
      year and respondent characteristics. Results. Statistically significantly higher
      ProTan scores were found for age group (strong reverse dose-response effect),
      male sex, residence (highest in Auckland), ethnicity (highest among Europeans),
      and sun sensitivity (an n-shaped association). There was no statistically
      significant change in total ProTan scores from baseline. Conclusions. The
      development, pretesting, and evaluation of messages for those groups most likely
      to endorse ProTan statements should be considered for the New Zealand skin cancer
      prevention program. To achieve and embed significant change, mass media campaigns
      may require greater intensity and reinforcement with sustained contextual support
      for settings-based behavioural change. 

PMID- 24660065
TI  - Polypeptide multilayer self-assembly studied by ellipsometry.
AB  - A polypeptide nanofilm made by layer-by-layer (LbL) self-assembly was built on a
      surface that mimics nonwoven, a material commonly used in wound dressings. Poly-L
      lysine (PLL) and poly-L-glutamic acid (PLGA) are the building blocks of the
      nanofilm, which is intended as an enzymatically degradable lid for release of
      bactericides to chronic wounds. Chronic wounds often carry infection originating
      from bacteria such as Staphylococcus aureus and a release system triggered by the
      degree of infection is of interest. The dry nanofilm was studied with
      ellipsometry. The thickness of the nanofilm was 60% less in its dry state than in
      its wet state. The measurements showed that a primer was not necessary to build a
      stable nanofilm, which is practically important in our case because a
      nondegradable primer is highly unwanted in a wound care dressing. Added V8
      (glutamyl endopeptidase) enzymes only showed adsorption on the nanofilm at room
      temperature, indicating that the PLL/PLGA "lid" may remain intact until the
      dressing has been filled with wound exudate at the elevated temperature typical
      of that of the wound. 

PMID- 24660066
TI  - Preparation and the biopharmaceutical evaluation for the metered dose transdermal
      spray of dexketoprofen.
AB  - The objective of the present work was to develop a metered dose transdermal spray
      (MDTS) formulation for transdermal delivery of dexketoprofen (DE). DE release
      from a series of formulations was assessed in vitro. Various qualitative and
      quantitative parameters like spray pattern, pump seal efficiency test, average
      weight per metered dose, and dose uniformity were evaluated. The optimized
      formulation with good skin permeation and an appropriate drug concentration and
      permeation enhancer (PE) content was developed incorporating 7% (w/w, %) DE, 7%
      (v/v, %) isopropyl myristate (IPM), and 93% (v/v, %) ethanol. In vivo
      pharmacokinetic study indicated that the optimized formulation showed a more
      sustainable plasma-concentration profile compared with the Fenli group. The
      antiinflammatory effect of DE MDTS was evaluated by experiments involving egg
      albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic
      acid-induced abdominal constriction was used to evaluate the anti-nociceptive
      actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good
      anti-inflammatory and anti-nociceptive activities. Besides, skin irritation
      studies were performed using rat as an animal model. The results obtained show
      that the MDTS can be a promising and innovative therapeutic system used in
      transdermal drug delivery for DE. 

PMID- 24660067
TI  - Increasing the Efficacy of SLNB in Cases of Malignant Melanoma Located in Close
      Proximity to the Lymphatic Basin.
AB  - Background. Being predictive of the entire nodal bed, sentinel lymph node biopsy
      (SLNB) is invaluable in the surgical management of melanoma. Although the concept
      is simple, sentinel lymph node (SLN) identification and removal can be
      technically challenging. Methods. A total of 102 consecutive patients have
      undergone SLNB in the Division of Plastic and Reconstructive Surgery of Soroka
      University Medical Center from 2009 to 2012. Patients have undergone SLNB using a
      radioactive tracer and blue stain in order to identify the SLN. Although SLNB
      usually precedes the wide excision of melanoma, primary lesions in close
      proximity (<10 cm) to the lymph basin require wide excision before beginning the
      SLN quest. Results. All pathology reports confirmed the excision of lymph nodes.
      Conclusions. When treating MM in close proximity to the lymph basin, changing the
      sequence of the SLNB procedure seems to increase the efficacy of the method. 

PMID- 24660068
TI  - Relation between Red Cell Distribution Width and Left Ventricular Function in
      Children with Heart Failure.
AB  - Background. Most of the studies done on adults showed that red cell distribution
      width (RDW) can be used as a prognostic marker in patients with chronic heart
      failure. However, RDW has not been tested in children with heart failure. Methods
      and Results. 31 children with heart failure admitted to Cardiology Unit, Tanta
      University Hospital, during the period of January 2012 to December 2012 were
      included in this study, RDW as a component of routine blood count was evaluated
      and correlated to the echocardiographic parameters of left ventricle. The mean
      age of our cohort was 16.16 +/- 14.97 months, congenital heart disease with left
      to-right shunt represented 58.1% of the underlying causes of heart failure while
      dilated cardiomyopathy made 41.9%. The mean hemoglobin level was 9.14 +/- 1.18
      gm/dL; RDW level ranged from 10.7% to 27.7% with a mean of 16.01 +/- 3.34.
      Hemoglobin was significantly correlated with RDW at any level. For the echo
      parameters, at cutoff point of 16.4%, RDW was significantly correlated with
      fraction shortening (FS), and A, E/A ratio, but it was not correlated with LVEDD,
      LVESD, and E/E at the same cutoff level. Conclusion. RDW, a simple, available
      test, can be used as a marker for the left ventricular function in children with
      heart failure until an echocardiography assessment for the patients is done. 

PMID- 24660069
TI  - Myocardial injury in critically ill children: a case control study.
AB  - Objectives. The aim of this study was to investigate the occurrence of myocardial
      injury in critically ill children through assessment of cardiac troponin T levels
      and whether levels are associated with disease severity and myocardial
      dysfunction measured by echocardiography. Methods. Over a 6-month period, this
      case control study included 50 patients admitted to Pediatric Intensive Care Unit
      of Zagazig University Children's Hospital. Twenty-five healthy children were
      included as a control group. Demographic and clinical data including the
      pediatric index of mortality II score were recorded. Echocardiographic
      examination was done and level of cardiac troponin T was measured using Elecsys
      Troponin T STAT Immunoassay. Results. Cardiac troponin T levels were
      significantly higher in critically ill in comparison to healthy children (median
      22 (18-28) pg/mL versus 10 (10-10) pg/mL, P < 0.05). Cardiac troponin T levels
      correlated positively with duration of ventilation as well as with disease
      severity and correlated negatively with left ventricular fractional shortening.
      Moreover, cardiac troponin T levels were significantly higher in nonsurvivors
      when compared to survivors (median 34.5 (27.5-41.5) pg/mL versus 20 (18-24)
      pg/mL, P < 0.05). Conclusion. In critically ill children, cardiac troponin T
      levels were elevated and were associated with duration of ventilation and disease
      severity. 

PMID- 24660070
TI  - Arteriovenous malformation of the oral cavity.
AB  - Vascular anomalies are a heterogeneous group of congenital blood vessel disorders
      more typically referred to as birthmarks. Subcategorized into vascular tumors and
      malformations, each anomaly is characterized by specific morphology,
      pathophysiology, clinical behavior, and management approach. Hemangiomas are the
      most common vascular tumors. Lymphatic, capillary, venous, and arteriovenous
      malformations make up the majority of vascular malformations. Arteriovenous
      malformation of the head and neck is a rare vascular anomaly but when present is
      persistent and progressive in nature and can represent a lethal benign disease.
      Here we present a case report of a 25-year-old male patient with arteriovenous
      malformation involving the base of tongue. 

PMID- 24660071
TI  - An Immature Type II Dens Invaginatus in a Mandibular Lateral Incisor with Talon's
      Cusp: A Clinical Dilemma to Confront.
AB  - Dens invaginatus (DI) is a malformation of teeth probably resulting from an
      infolding of the dental papilla during tooth development. DI is classified as
      type I, II, and III by Oehlers depending on the severity of malformation. The
      maxillary lateral incisor is the most commonly affected tooth. Structural defects
      do exist in the depth of the invagination pits, and as a consequence, the early
      development of caries and the subsequent necrosis of the dental pulp, as well as
      abscess and cyst formation are clinical implications associated with DI.
      Occasionally, we can see more than one developmental anomaly occurring in a
      single tooth. In such cases it becomes important to identify the anomalies and
      initiate a proper treatment plan for good prognosis. In this paper, an unusual
      case of DI which clinically presented as a huge talons cusp affecting a
      mandibular lateral incisor tooth is described. This case report illustrates
      grinding of the talons cusp followed by nonsurgical endodontic management of dens
      invaginatus type II with an immature apex and periapical lesions, in which
      Mineral Trioxide Aggregate (MTA) shows a complete periapical healing with bone
      formation at the site of the lesions. 

PMID- 24660072
TI  - Three-year successful cinacalcet treatment of secondary hyperparathyroidism in a
      patient with x-linked dominant hypophosphatemic rickets: a case report.
AB  - Hypophosphatemic rickets (HR) is a rare inherited disorder characterized by a
      classic rickets phenotype with low plasma phosphate levels and resistance to
      treatment with vitamin D. Development of secondary hyperparathyroidism (SHPT) as
      a direct consequence of treatment is a frequent complication and a major clinical
      challenge, as this may increase risk of further comorbidity. Cinacalcet, a
      calcimimetic agent that reduces the secretion of PTH from the parathyroid glands,
      has been suggested as adjuvant treatment to SHPT in patients with HR. However,
      only two papers have previously been published and no data are available on
      effects of treatment for more than six months. We now report a case of 3-year
      treatment with cinacalcet in a patient with HR complicated by SHPT. A 53-year-old
      woman with genetically confirmed X-linked dominant hypophosphatemic rickets
      developed SHPT after 25 years of conventional treatment with alfacalcidol and
      phosphate supplements. Cinacalcet was added to her treatment, causing a sustained
      normalization of PTH. Ionized calcium decreased, requiring reduction of
      cinacalcet, though asymptomatical. Level of phosphate was unchanged, but alkaline
      phosphatase increased in response to treatment. Cinacalcet appeared to be
      efficient, safe, and well tolerated. We recommend close control of plasma calcium
      to avoid hypocalcemia. 

PMID- 24660073
TI  - Life-threatening hypokalemic paralysis in a young bodybuilder.
AB  - We report a case of life-threatening hypokalemia in a 28-year-old bodybuilder who
      presented with sudden onset bilateral lower limbs paralysis few days after his
      bodybuilding competition. His electrocardiogram (ECG) showed typical u-waves due
      to severe hypokalemia (serum potassium 1.6 mmol/L, reference range (RR) 3.5-5.0
      mmol/L). He was admitted to the intensive care unit (ICU) and was treated with
      potassium replacement. The patient later admitted that he had exposed himself to
      weight loss agents of unknown nature, purchased online, and large carbohydrate
      loads in preparation for the competition. He made a full recovery after a few
      days and discharged himself from the hospital against medical advice. The severe
      hypokalemia was thought to be caused by several mechanisms to be discussed in
      this report. With the ever rising number of new fitness centers recently, the
      ease of online purchasing of almost any drug, and the increasing numbers of
      youngsters getting into the bodybuilding arena, clinicians should be able to
      recognize the possible causes of sudden severe hypokalemia in these patients in
      order to revert the pathophysiology. 

PMID- 24660074
TI  - Germinoma with involvement of midline and off-midline intracranial structures.
AB  - Germinomas are malignant intracranial germ tumors, usually found in suprasellar
      regions. Less than 10% are localized in off-middle structures, and synchronous
      involvement of both structures has only exceptionally been published. A case of
      an 18-year-old male patient with progressive right-sided hemiparesis and
      panhypopituitarism was reviewed. Brain MRI showed a solid mass involving
      pituitary and hypothalamus with thickening of pituitary stalk, high intensity
      lesions on T2-weighted imaging in left internal capsule, caudate nucleus, globus
      pallidus, and mild atrophy of the left internal capsule and cerebral peduncle.
      Nonadenomatous lesions were considered in the differential diagnosis. Alfa
      fetoprotein (AFP) levels were negative in both serum and cerebrospinal fluid
      (CSF), while beta -human chorionic gonadotrophin ( beta -HCG) levels were
      slightly increased in CSF. A transsphenoidal biopsy identified a germinoma. Four
      cycles of chemotherapy with bleomicine, etoposide, and cysplatin were given,
      followed by radiotherapy, but patients died due to a recidiva. Conclusion.
      Germinoma must be considered in patients with insipidus diabetes with a sellar
      mass with thickening of pituitary stalk; and ectopic germinoma must be suspected
      in patients with slowly progressive hemiparesis with cerebral hemiatrophy. Even
      with a rare condition, colocalization of midline and off-midline germinoma must
      be suspected in the presence of these typical signs of both localizations. 

PMID- 24660075
TI  - A Paternally Inherited BRCA1 Mutation Associated with an Unusual Aggressive
      Clinical Phenotype.
AB  - This report highlights the necessity of genetic testing, at least for BRCA1
      mutations, of young females diagnosed with triple negative breast cancer, even in
      the absence of or limited family history. A 34-year-old female with a locally
      advanced, triple negative tumour, which perforated the skin, is described. At the
      time of diagnosis, the patient had already multiple lung metastases and although
      chemotherapy was started immediately, she died with rapid systemic disease
      progression. The patient was found to carry the BRCA1 p.E1060X mutation, which is
      located on exon 11 of the gene. The high penetrance of BRCA1 gene is not
      represented in the patient's family, since the mutation was paternally inherited.
      It is evident that females belonging to small families, along with paternal
      inheritance of pathogenic BRCA mutations that predispose for breast cancer, in
      most cases will probably be genetically tested only after being diagnosed with
      cancer. 

PMID- 24660076
TI  - Successful Outcome of Chronic Intrahepatic Cholestasis in an Adult Patient with
      Sickle Cell/ beta (+) Thalassemia.
AB  - Sickle cell/beta (+) thalassemia (Hb S/beta (+)thal) is considered as a variant
      form of sickle cell disease. Acute episodes of vasoocclusive pain crisis are
      characteristic for sickle cell disorders and may be complicated by an acute or
      chronic life-threatening organ dysfunction. Chronic intrahepatic cholestasis is a
      rare and severe complication in sickle cell disease, characterized by marked
      hyperbilirubinemia and acute hepatic failure with an often fatal course. Despite
      the fact that patients with Hb S/beta (+)thal usually have a mild type of
      disease, herein we describe an interesting case of chronic intrahepatic
      cholestasis with successful outcome in an adult patient with Hb S/beta (+)thal. 

PMID- 24660077
TI  - Epstein-barr virus infection in an elderly nonimmunocompromised adult
      successfully treated with rituximab.
AB  - Epstein-Barr virus (EBV) is a ubiquitous virus that commonly affects children and
      adolescents. In addition to causing a viral illness, it is also associated with
      various malignancies in particular B cell lymphomas and lymphoproliferative
      disorders. Differentiating between the two processes can be a diagnostic
      challenge. Here, we present a case of an atypical EBV infection in an elderly
      patient with severe systemic symptoms, multiorgan involvement, lymphadenopathy,
      and negative EBV serology. Excisional lymph node biopsy demonstrated features of
      a lymphoproliferative process involving EBV. Despite supportive care, she
      experienced continued clinical deterioration and was successfully treated with
      rituximab. This case illustrates the diagnostic challenges of these cases
      particularly in the elderly who may have age related immunosenescence, the
      utility of EBV PCR testing, and the clinical efficacy of rituximab in clearing
      the infected cells. 

PMID- 24660078
TI  - Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third
      Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a
      Second Relapse.
AB  - Although hematopoietic stem cell transplantation (HSCT) has been considered to be
      the only way for potential cure of relapsed acute myeloid leukemia (AML), there
      has been no report on a third HSCT in patients with multiple relapsed AML. Here,
      we report a case of 53-year-old female who received a successful third allogeneic
      HSCT after relapse of AML following a second allogeneic HSCT. She was treated
      with a toxicity reduced conditioning regimen and received direct intrabone cord
      blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as
      a graft source. Graft-versus-host disease prophylaxis was performed with a single
      agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission
      for 8 months since the direct intrabone CBT. This report highlights not only the
      importance of individually adjusted approach but also the need for further
      investigation on the role of HSCT as a treatment modality in patients with
      refractory or multiple relapsed AML. 

PMID- 24660079
TI  - Leiomyoma in vulva: a diagnostic dilemma.
AB  - With the help of this case we summarize some crucial features to be picked up
      from history and examination before labeling a case as Bartholin's abscess or
      cyst. A 20-year old unmarried girl, deaf and mute since birth, was initially
      diagnosed to have Bartholin's abscess. On careful reexamination after
      inflammation subsided, a decision of excision of this tumor was taken.
      Intraoperatively it was found to be well encapsulated. Histopathology ascertained
      the diagnosis of vulval leiomyoma. 

PMID- 24660080
TI  - Concomitant imperforate hymen and transverse vaginal septum complicated with
      pyocolpos and abdominovaginal fistula.
AB  - A 13-year-old patient with a complaint of worsening lower abdominal pain during
      the past 4 months was admitted to the emergency department. An abdominopelvic
      ultrasound scan revealed a distended uterocervical cavity suggestive of
      hematometrocolpos. Imperforate hymen was observed on examination of the external
      genitalia. MRI scan revealed an air-fluid level representing pyometrocolpos
      within a distended vagina. Posterior vaginal extraperitoneal leakage as the sign
      of a fistula between the vagina and the rectovaginal space was detected. Although
      laparoscopic approach was planned, malodorous pus expelled after the insertion of
      the Veress needle, it was decided to proceed to laparotomy. Pus with peritoneal
      microabscess formations was observed at laparotomy. The imperforate hymen and TVS
      were excised vaginally. A more complex anomaly should be suspected in cases with
      hematometra and concomitant imperforated hymen without any bulging and thorough
      evaluation using radiological imaging techniques should be performed before
      surgical approach. 

PMID- 24660082
TI  - Partial laryngectomy with cricoid reconstruction: thyroid carcinoma invading the
      larynx.
AB  - Laryngotracheal invasion worsens the prognosis of thyroid cancer and the surgical
      approach for laryngotracheal invasion is controversial. In this paper, partial
      full-thickness excision of the cricoid cartilage with supracricoid laryngectomy
      and reconstruction of existing defect with thyroid cartilage are explained in a
      patient with papillary thyroid carcinoma invading the thyroid cartilage and
      cricoid cartilage without intraluminal invasion. Surgical indication should not
      be established by the site of involvement in thyroid carcinomas invading the
      larynx, as in primary cancers of the larynx. We think that partial laryngectomy
      according to the involvement site and the appropriate reconstruction techniques
      should be used for thyroid cancer invading the larynx. 

PMID- 24660081
TI  - A case of endometrioid adenocarcinoma arising from adenomyosis.
AB  - Malignant changes in endometriosis are often reported, but those in adenomyosis
      are rare. We report a case of endometrioid adenocarcinoma arising from
      adenomyosis. Case Presentation. A 57-year-old woman presenting with vaginal
      bleeding was referred to our hospital. Cytological tests of endometrium revealed
      atypical glandular cells. Fractional endometrial curettage revealed normal
      endometrium without atypia. Magnetic resonance imaging (MRI) revealed multiple
      myomas. The endometrium was slightly enhanced on T1-weighted imaging and
      endometrial cancer was suspected. Myometrial invasion was not evident. The
      patient was admitted and semiradical hysterectomy with bilateral salpingo
      oophorectomy and pelvic lymphadenectomy was performed. Histopathological study
      revealed grade 1 endometrioid adenocarcinoma. Although the lesion was located in
      the muscle layer of the corpus and invaded more than half of it, the endometrium
      was intact. Pelvic lymph node metastasis was noticed. No cervical invasion or
      metastasis to the adnexa was seen. We diagnosed the case with a stage 1B
      endometrioid adenocarcinoma originating from adenomyosis. Adjuvant chemotherapy
      was then performed in the form of 5 cycles of paclitaxel (180 mg/m(2)) and
      carboplatin (AUC = 5). Five years later, right lung metastasis and right para
      aortic and pelvic lymph nodes metastasis were noticed. Paclitaxel and carboplatin
      are now being administered. 

PMID- 24660083
TI  - Idiopathic infantile arterial calcification: a possible cause of refractory
      cardiopulmonary failure in infancy.
AB  - Idiopathic Infantile Arterial Calcification is a rare autosome recessive disease
      characterized by extensive calcification of medium and large arteries. Loss-of
      function mutations in ectonucleotide pyrophosphatase/phosphodiesterase 1 gene
      have been described in more than 80% of the cases. Although the diagnosis is
      usually made at autopsy, it is possible to identify cases based on clinical
      presentation, radiology findings, and molecular studies. Appropriate treatment
      can be initiated and has been shown to successfully induce permanent remission.
      We report a 4-week-old neonate who initially presented with respiratory distress,
      heart failure, and Coxsackie B viremia suggestive of viral induced
      cardiomyopathy. His symptoms progressed to multiple organ failure and he
      eventually expired at four weeks of age. On autopsy, diffuse calcium deposition
      within the internal elastic lamina of medium and large arteries was identified,
      as well as narrowing of lumen due to myointimal proliferation. This case report
      will emphasize the importance of taking this rare curable disease into
      consideration in all cases of infants with cardiopulmonary failure. 

PMID- 24660084
TI  - Metastatic squamous cell carcinoma of the anus to the lung confirmed with
      allelotyping.
AB  - Histopathologic techniques are insufficient for distinguishing primary squamous
      cell carcinoma (SCC) from metastatic SCC, which is clinically important. A
      patient with SCC of the anus was found to also have SCC of the lung, and the
      question of metastatic versus synchronous primary diseases was raised.
      Immunohistochemical and hematoxylin and eosin (H&E) staining on sections of
      tissue could not discriminate between the two entities. Immunostain for p16 and
      chromogenic in situ hybridization for human papillomavirus (HPV) type 16 were
      positive in both tumors. Additionally, allelotyping for loss of heterozygosity
      displayed similar findings and confirmed the histopathological impression of anal
      SCC metastasis to the lung. The patient was treated with palliative chemotherapy
      instead of additional surgical treatment. When multiple tumors are present,
      determining metastatic versus synchronous primary tumors is necessary for
      appropriate treatment. Identification can be achieved using allelotyping for loss
      of heterozygosity. 

PMID- 24660085
TI  - Ramsay hunt syndrome in a patient with rheumatoid arthritis after treatment with
      infliximab.
AB  - A 39-year-old female patient with rheumatoid arthritis developed Ramsay Hunt
      syndrome after infliximab treatment. This condition is caused by the reactivation
      of varicella zoster virus infection in the geniculate ganglion of facial nerve in
      the host's immunosuppression. She was treated immediately with valaciclovir and
      hydrocortisone, and the complete recovery was achieved at 6 months after the
      onset. This is the first report of Ramsay Hunt syndrome as an adverse effect of
      infliximab in rheumatoid arthritis. 

PMID- 24660086
TI  - Atrioventricular left ventricular apical pacing improves haemodynamic,
      rotational, and deformation variables in comparison to pacing at the lateral wall
      in intact myocardium: experimental study.
AB  - Aim. To assess the effect on left ventricular (LV) function of atrioventricular
      (AV) and ventricular pacing at the LV apical or lateral wall and to compare the
      normal torsional and deformation pattern of the intact LV myocardium with those
      created by the aforementioned LV pacing modes and sites. Methods. Experiments
      were conducted in pigs (n = 21) with normal LV function to investigate the acute
      hemodynamic effects of epicardial AV and ventricular LV pacing at the LV apical
      or lateral wall. Torsional and deformation indices of LV function were assessed
      using speckle tracking echocardiography. Results. AV pacing at the apex revealed
      a significant reduction in the radial strain of the base (P < 0.03), without
      affecting significantly the ejection fraction and the LV torsion or twist. In
      contrast, AV pacing at the lateral wall produced, in addition to the reduction of
      the radial strain of the base (P < 0.01), significant reduction of the
      circumferential and the radial strain of the apex (both P < 0.01) as well as of
      the ejection fraction (P < 0.002) and twist (P < 0.05). Conclusions. In pig
      hearts with intact myocardium, LV function is maintained at sinus rhythm level
      when AV pacing is performed at the LV apex. 

PMID- 24660087
TI  - The Relationship between Selenium and T3 in Selenium Supplemented and
      Nonsupplemented Ewes and Their Lambs.
AB  - Twenty pregnant ewes were selected and classified into two groups. The first
      group received subcutaneous selenium supplementation (0.1 mg of sodium
      selenite/kg BW) at the 8th and 5th weeks before birth and 1st week after birth
      while the other was control group without selenium injection. Maternal plasma and
      serum samples were collected weekly from the 8th week before birth until the 8th
      week after birth and milk samples were taken from ewes weekly, while plasma and
      serum samples were collected at 48 hours, 1st, 2nd, 3rd, 5th, and 8th weeks after
      birth from the newborn lambs. Results demonstrated significant positive
      relationship between maternal plasma selenium and serum T3 in supplemented and
      control ewes (r = 0.69 to 0.72, P < 0.05). There was significant (P < 0.001)
      increase in T3 in supplemented ewes and their lambs until the 8th week after
      birth. There was positive relationship between milk, selenium concentration, and
      serum T3 in the newborn lambs of the supplemented group (r = 0.84, P < 0.01),
      while the relationship was negative in the control one (r = -0.89, P < 0.01).
      Muscular and thyroid pathological changes were independent of selenium
      supplementation. Selenium supplementation was important for maintaining T3 in
      ewes and newborn lambs until the 8th week after birth. 

PMID- 24660088
TI  - Prevalence of dermatological presentations of canine leishmaniasis in a
      nonendemic area: a retrospective study of 100 dogs.
AB  - This retrospective study determined the prevalence of dermatological lesions
      associated with canine leishmaniasis (CanL) in a nonendemic area in Italy. The
      medical records of 131 dogs with CanL were reviewed and, of these, 115/131 dogs
      (88%) had dermatological manifestations of which 100/131 dogs (76%) met the
      inclusion criteria. Sixty-two percent of dogs were male and 38% were female and
      the mean age was 6.4 years. Thirty-two percent of dogs were mixed breeds; the
      remainder represented a variety of pure breeds. In 79% of dogs dermatological
      signs occurred in association with systemic signs of CanL, whilst 21% of dogs had
      only dermatological manifestations. The most common dermatological manifestation
      was exfoliative dermatitis (74%), followed by ulcerative (18%) and nodular (11%)
      lesions. In 51% of dogs the lesions were localized mainly on the pinnae, head,
      and pressure points; in the remaining 49% lesions were generalized. The only
      statistically significant association was between Retriever breed and animals
      with only dermatological signs (P = 0.0034, OD 5.97, CI 0.996-37.933). In this
      study dermatological manifestations of CanL were very commonly reported, and
      their prevalence is similar to previous studies in endemic areas despite the fact
      that dogs living in nonendemic areas are not exposed to repeated infectious bites
      and continuous stimulation of the dermal immune system. 

PMID- 24660089
TI  - Preliminary study of the influence of red blood cells size on the determinism of
      the breed in cattle.
AB  - This study was carried out on five cattle groups, local, cross, Prim'Holstein,
      Montbeliard, and Brown of the Alps, in order to study the influence of breed on
      erythrocytes diameter. For each breed, blood samples were taken from 15 adult
      females by jugular venipuncture; blood smears were made on slides immediately
      after the blood collection and stained according to the method of May-Grundwald
      Giemsa. Morphometric study was realized using the OPTIKA Pro Vision software. The
      statistical analysis was assessed by using the descriptive boxplots test and
      ANOVA. The size of red blood cells is greater in the imported Brown of the Alps
      breed (5,32 +/- 0,19) and also in our local breed (5,23 +/- 0,10), whereas they
      were smaller in the Montbeliard breed (4,79 +/- 0,21). This investigation allowed
      us to show that from a drop of blood we can have an idea of the bovine breeds,
      taking into account the size of the erythrocytes. 

PMID- 24660090
TI  - Simultaneous determination and pharmacokinetic comparisons of multi-ingredients
      after oral administration of radix salviae miltiorrhizae extract, hawthorn
      extract, and a combination of both extracts to rats.
AB  - A simple and sensitive HPLC method was developed for simultaneous determination
      of danshensu (DSS), rosmarinic acid (RA), lithospermic acid (LA), salvianolic
      acid B (SAB), and hyperoside (HP) in rat plasma. This method validated was
      successfully applied to the pharmacokinetic study of the main active ingredients
      after oral administration of Radix Salviae Miltiorrhizae extract (SME), hawthorn
      extract (HTE), and a combination of both extracts (2.5 : 1) to rats. The results
      indicated that there have been great differences in pharmacokinetics between a
      single extract and a combination of both extracts. A combination of both extracts
      can enhance their bioavailabilities and delay the elimination of SAB and DSS in
      rats. 

PMID- 24660091
TI  - Smoking and Pancreatic Disease.
AB  - Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer.
      However, the mechanisms through which it causes the diseases remain unknown. In
      the present manuscript we reviewed the latest knowledge gained on the effect of
      cigarette smoke and smoking compounds on cell signaling pathways mediating both
      diseases. We also reviewed the effect of smoking on the pancreatic cell
      microenvironment including inflammatory cells and stellate cells.

PMID- 24660092
TI  - Total hip arthroplasty for hip fractures: 5-year follow-up of functional outcomes
      in the oldest independent old and very old patients.
AB  - INTRODUCTION: This study aimed to determine the dislocation and reoperation rate,
      functional outcomes, and the survival rate of the unique subset of very old but
      lucid and independent patients with hip fractures following a total hip
      arthroplasty (THA) and geriatric team-coordinated perioperative care. METHOD:
      Between 2000 and 2006, previously independent ambulatory patients >=80 years old
      presenting with an intracapsular hip fracture were given THAs under the care of
      an integrated orthopedic surgery-geriatric service. Their fracture-related
      complications, ambulation, mental status, and survival were followed for 5 to 11
      years postinjury. RESULTS: Five years postinjury, 57 (61.3%) patients of the
      original study group were living. In all, 3 (3.2%) patients had postoperative hip
      dislocations (and 2 patients had dislocation twice) and 2 reoperations were
      needed within the first postoperative month. There were no hip dislocations or
      reoperations after the first year. Radiographs obtained on 88% of the surviving
      patients at 5 years postoperatively showed that all remained unchanged from their
      immediate postoperative images. Nearly half of the patients were still able to
      ambulate as they did preoperatively and their mixed-model equation was
      statistically unchanged. CONCLUSION: This study of patients >80 years old with
      previously good functional status demonstrates that with appropriate surgical
      (best prosthesis, good operating technique, and regional anesthesia) and
      geriatric (pre- and postoperative assessments, close follow-up, medication
      adjustments, and fall-prevention instruction) care, they have few hip
      dislocations and reoperations, survive postfracture at least as long as their
      noninjured contemporaries, and continue to function and ambulate as they did
      prior to their injury.

PMID- 24660093
TI  - Open reconstruction of complex proximal metadiaphyseal fragility fractures of the
      humerus.
AB  - PURPOSE: A proactive surgical and rehabilitation protocol was implemented to
      manage humeral fractures involving both the proximal end and shaft in an older
      patient population. Primary treatment goals were early return to function and
      reliable fracture union with minimal complications. METHODS: From 2008 to 2012,
      21 such operations were performed; 18 were considered "fragility" fractures based
      on mechanism, patient age, and evidence of osteopenia or osteoporosis. Open
      reduction and internal fixation (ORIF) was employed using direct reduction and
      fixation with a long periarticular locking plate. Physiotherapy was commenced 2
      weeks postoperatively. The Disabilities of the Arm, Shoulder, and Hand (DASH)
      questionnaire was used to assess functional outcome at a time point greater than
      1 year postoperative. RESULTS: The study group consisted primarily of elderly
      females (83% with a median age of 69 years) whom sustained complex metadiaphyseal
      proximal humeral fractures after simple mechanical fall (78%). Uneventful union
      occurred in all cases. Local complications included 1 case of partial radial
      nerve palsy, which had resolved completely by 1 year. No cases of infection were
      identified. Long-term return to functionality was evident with a median DASH
      score of 12 (mean = 21, standard deviation = 20, n = 13). Seventy five percent of
      patients reported minimal or no pain (question [Q] 24), and 75% achieved return
      of overhead function (Q6, 12, and 15). CONCLUSION: Treatment of complex
      metadiaphyseal fragility fractures with anatomic reduction, fixed angle plating,
      and early physiotherapy returns the older patient to optimized functionality with
      minimal risk of complication. The DASH outcomes are equivalent to ORIF of
      isolated proximal humerus fractures and clinically indistinguishable from the
      general population.

PMID- 24660094
TI  - Propagation of bisphosphonate-related femoral stress fractures despite femoral
      nailing: a cautionary tale from 2 cases.
AB  - We report 2 cases of atypical femoral fracture displacement despite treatment
      with intramedullary (IM) nailing. Both patients had received more than 3 years of
      bisphosphonates. One patient had prophylactic fixation of an atypical femur
      fracture due to intractable pain. The other had undergone nailing previously for
      a traumatic shaft fracture. The patient then received bisphosphonate later and
      sustained an atypical fracture with the nail in place. Both femoral nails were
      slotted, cannulated stainless steel piriformis entry designs. These 2 cases are
      among the first reported failures of IM fixation in preventing displacement of a
      bisphosphonate stress fracture. We advice caution when using slotted nails in
      prophylaxis of atypical femur fractures because of its significantly reduced
      torsional stiffness compared to modern nonopen sectioned nails. 

PMID- 24660095
TI  - A painful finger as first sign of a malignancy.
AB  - INTRODUCTION: Bone metastases are frequently seen in patients with malignancies,
      but only 0.007% to 0.3% of these metastases are located in the hand or foot. In
      16%, the metastasis is the first manifestation of a malignancy. These
      acrometastases have a poor prognoses with a median survival of 6 months.
      Treatment is usually palliative and consists of radiation or amputation. CASE
      DESCRIPTION: An 83-year-old woman was seen with pain and swelling of the right
      middle finger since 3 months. A radiograph of this finger showed a lytic lesion
      of the proximal phalanx. A metastasis, primary bone tumor, or osteomyelitis was
      considered. Because of a radically resected colon carcinoma in patient's medical
      history, the carcinoembryonic antigen level was analyzed and proved to be
      elevated. Computed tomography scan of thorax and abdomen showed 2 (primary)
      pulmonary tumors with mesenteric metastases. Patient refrained from further
      analysis and treatment of these lung tumors. However, because of persistent pain
      the right middle finger was amputated. Pathological examination of the finger
      confirmed the diagnosis of an adenocarcinoma most likely to be a metastasis of
      lung cancer. Lung cancer is in most cases responsible for metastases in the hand.
      CONCLUSION: Acrometastasis may be the first manifestation of malignancy. Given
      the poor prognosis, early diagnosis is important to offer adequate treatment.
      Delay of appropriate treatment can adversely affect the quality of life in these
      often preterminal patients. This case report could contribute to a (more) rapid
      recognition of acrometastases as patients with acrometastases are often presented
      to specialists who do not frequently deal with cancer.

PMID- 24660096
TI  - The prevalence of radiographic criteria of femoral acetabular impingement in
      patients undergoing hip arthroplasty surgery.
AB  - BACKGROUND: Pistol grip deformity of the proximal femur has been reported as a
      potential cause of hip pain and early-onset arthritis. The exact incidence of
      patients with osteoarthritis resulting from femoral acetabular impingement (FAI)
      is unknown. The purpose of this study was to explore the relationship between
      radiographic markers of FAI in patients undergoing hip arthroplasty. METHODS: We
      retrospectively reviewed the radiographs of patients undergoing hip arthroplasty
      by a single surgeon over a 2-year period. The patients were divided by age, those
      younger than 65 years and (group A) and those 65 years and older (group B). The
      radiographs were evaluated for morphology consistent with FAI including an alpha
      angle >55 degrees , crossover sign, coxa profunda, acetabular protrusio, and
      ischial spine sign. Three independent reviewers evaluated all the radiographs.
      The incidence of CAM, Pincer, and mixed deformities were compared between the 2
      groups. RESULTS: A total of 255 patients with 258 hip arthroplasties were
      included in this analysis. Group A was found to have a greater number of patients
      with CAM morphology. Linear regression analysis revealed that the alpha angle was
      greater in younger patients. CONCLUSION: Patients undergoing hip arthroplasty
      exhibit a high incidence of radiographic abnormalities consistent with FAI. The
      CAM-type morphology occurs more frequently in younger patients with advanced
      arthritis requiring hip arthroplasty. This morphology is thought to cause a
      delaminating injury to the cartilage of the acetabulum. This study supports the
      notion that CAM-type morphology is a risk factor for early development of
      degenerative arthritis of the hip.

PMID- 24660097
TI  - Do elderly patients fare worse following operative treatment of distal femur
      fractures using modern techniques?
AB  - BACKGROUND: The purpose of this study was to compare the functional outcomes and
      quality of life of older and younger patients with similarly treated distal femur
      fractures. METHODS: We conducted an assessment of 57 patients who sustained
      distal femur fractures (Orthopaedic Trauma Association Type 33B, C) and underwent
      surgical treatment at our academic medical center. Patients were divided into 2
      groups for analysis: an elderly cohort of patients aged 65 or older and a
      comparison cohort of patients younger than age of 65. A retrospective review of
      demographics, preoperative ambulatory status, radiographic data, and physical
      examination data was collected from the medical records. Follow-up functional
      data were collected via telephone at a mean of 2.5 years (range 6 months-8 years)
      using a Short Musculoskeletal Functional Assessment (SMFA). All patients
      underwent standard operative treatment of either nail or plate fixation. RESULTS:
      There was no statistical difference in gender, fracture type, surgical technique,
      surgeon, or institution where the surgery was performed. The percentage of
      patients with healed fractures at 6-months follow-up was not significantly
      different between the cohorts. The elderly cohort had slightly worse knee range
      of motion at 3, 6, and 12 months postoperatively but there was not a
      statistically significant difference between the groups. The SMFA Daily Activity,
      Functional, and Bother indices were significantly worse in the older cohort (P <
      .01, P = .01, P = .02, respectively). However, there was no significant
      difference in the SMFA Emotional or Mobility indices. CONCLUSION: Despite lower
      quality of life and functional scores, this study suggests that relatively good
      clinical outcomes can be achieved with surgical fixation of distal femoral
      fractures in the elderly patients. Age should not be used as a determinate in
      deciding against operative treatment of distal femur fractures in the elderly
      patients.

PMID- 24660098
TI  - Cooling Strategies Targeting Trauma.

PMID- 24660099
TI  - Therapeutic Hypothermia in Children and Adults with Severe Traumatic Brain
      Injury.
AB  - Great expectations have been raised about neuroprotection of therapeutic
      hypothermia in patients with traumatic brain injury (TBI) by analogy with its
      effects after heart arrest, neonatal asphyxia, and drowning in cold water. The
      aim of this study is to review our present knowledge of the effect of therapeutic
      hypothermia on outcome in children and adults with severe TBI. A literature
      search for relevant articles in English published from year 2000 up to December
      2013 found 19 studies. No signs of improvement in outcome from hypothermia were
      seen in the five pediatric studies. Varied results were reported in 14 studies on
      adult patients, 2 of which reported a tendency of higher mortality and worse
      neurological outcome, 4 reported lower mortality, and 9 reported favorable
      neurological outcome with hypothermia. The quality of several trials was low. The
      best-performed randomized studies showed no improvement in outcome by hypothermia
      some even indicated worse outcome. TBI patients may suffer from hypothermia
      induced pulmonary and coagulation side effects, from side effects of vasopressors
      when re-establishing the hypothermia-induced lowered blood pressure, and from a
      rebound increase in intracranial pressure (ICP) during and after rewarming. The
      difference between body temperature and temperature set by the biological
      thermostat may cause stress-induced worsening of the circulation and oxygenation
      in injured areas of the brain. These mechanisms may counteract neuroprotective
      effects of therapeutic hypothermia. We conclude that we still lack scientific
      support as a first-tier therapy for the use of therapeutic hypothermia in TBI
      patients for both adults and children, but it may still be an option as a second
      tier therapy for refractory intracranial hypertension.

PMID- 24660100
TI  - Comparative Effectiveness of Therapeutic Hypothermia After Out-of-Hospital
      Cardiac Arrest: Insight from a Large Data Registry.
AB  - This study was done to determine the effectiveness of therapeutic hypothermia
      (TH) after out-of-hospital cardiac arrest (OHCA) among a large cohort of adults
      in the Cardiac Arrest Registry to Enhance Survival (CARES), with an emphasis on
      subgroups with a nonshockable first documented rhythm. This was an IRB approved
      retrospective cohort study. All adult index events at participating sites from
      November 2010 to December 2013 were study eligible. All patient data elements
      were provided. Summary statistics were calculated for all patients with and
      without TH. For multivariate adjustment, a multilevel (i.e., hierarchical), mixed
      effects logistic regression (MLR) model was used with hospitals treated as random
      effects. Propensity score matching (PSM) on both shockable and nonshockable
      patients was done as a sensitivity analysis. After predefined exclusions, our
      final sample size was 6369 records for analysis: shockable=2992 (47.0%);
      asystole=1657 (26.0%); pulseless electrical activity=1249 (19.6%); other
      unspecified nonshockable=471 (7.4%). Unadjusted differences in neurological
      status at hospital discharge with and without TH were similar (p=0.295). After
      multivariate adjustment, TH had either no association with good neurological
      status at hospital discharge or that TH was actually associated with worse
      neurological outcome, particularly in patients with a nonshockable first
      documented rhythm (i.e., for NS patients, MLR odds ratio for TH=1.444; 95% CI
      [1.039, 2.006] p=0.029, and OR=1.017, p=0.927 via PSM). Highlighting our
      limitations, we conclude that when TH is indiscriminately provided to a large
      population of OHCA survivors with a nonshockable first documented rhythm,
      evidence for its effectiveness is diminished. We suggest more uniform and rigid
      guidelines for application.

PMID- 24660102
TI  - Polyisoprenylated methylated protein methyl esterase overexpression and
      hyperactivity promotes lung cancer progression.
AB  - The involvement of hyperactive polyisoprenylated proteins in cancers has
      stimulated the search for drugs to target and suppress their excessive
      activities. Polyisoprenylated methylated protein methyl esterase (PMPMEase)
      inhibition has been shown to modulate polyisoprenylated protein function. For
      PMPMEase inhibition to be effective against cancers, polyisoprenylated proteins,
      the signaling pathways they mediate and/or PMPMEase must be overexpressed,
      hyperactive and be involved in at least some cases of cancer. PMPMEase activity
      in lung cancer cells and its expression in lung cancer cells and cancer tissues
      were investigated. PMPMEase was found to be overexpressed and significantly more
      active in lung cancer A549 and H460 cells than in normal lung fibroblasts. In a
      tissue microarray study, PMPMEase immunoreactivity was found to be significantly
      higher in lung cancer tissues compared to the normal controls (p < 0.0001). The
      mean scores +/- SEM were 118.8 +/- 7.7 (normal), 232.1 +/- 25.1 (small-cell lung
      carcinomas), 352.1 +/- 9.4 (squamous cell carcinomas), 311.7 +/- 9.8
      (adenocarcinomas), 350.0 +/- 24.2 (papillary adenocarcinomas), 334.7 +/- 30.1
      (adenosquamous carcinomas), 321.9 +/- 39.7 (bronchioloalveolar carcinomas), and
      331.3 +/- 85.0 (large-cell carcinomas). Treatment of lung cancer cells with L-28,
      a specific PMPMEase inhibitor, resulted in concentration-dependent cell death
      (EC50 of 8.5 MUM for A549 and 2.8 MUM for H460 cells). PMPMEase inhibition
      disrupted actin filament assembly, significantly inhibited cell migration and
      altered the transcription of cancer-related genes. These results indicate that
      elevated PMPMEase activity spur cell growth and migration, implying the possible
      use of PMPMEase as a protein biomarker and drug target for lung cancer. 

PMID- 24660103
TI  - Sepantronium is a DNA damaging agent that synergizes with PLK1 inhibitor
      volasertib.
AB  - In a search for novel agents that boost the anti-neoplastic effects of polo-like
      kinase 1 (PLK1) inhibitor volasertib, we found that a sepantronium and volasertib
      combination at the nano mole concentration potently inhibited growth of various
      non-small cell lung cancer (NSCLC) cell lines than either drug alone in vitro.
      Combination use of volasertib with sepantronium inhibited adaptation of cells to
      polo arrest. Addition of sepantronium to volasertib prevented accumulation of
      survivin and cyclin B protein at a concentration causing no appreciable survivin
      down regulation. Sepantronium induced cell cycle arrest from G1 or G2/M phase.
      Further studies demonstrated DNA damage of cancer cells when they are treated
      with sepantronium, which is evidenced by induction of phospho-gammaH2AX. In line
      with induction of a DNA damage response in cancer cells, known DNA damage
      response sensors and transducers ATM, ATR, CHK1, CHK2, p53 are phosphorylated
      following drug treatment. Meanwhile, expression of CDKN1A, BAX and XRCC5 are
      induced at the mRNA level as determined by quantitative real time PCR. A single
      cell electrophoresis assay (Comet assay) of cells treated with sepantronium
      revealed severe DNA strand breaks. M-phase arrest does not increase the lethality
      of DNA damage by sepantronium as compared to G1 phase arrest. Knock down of
      survivin did not cause DNA damage. Hence, sepantronium is a DNA damaging agent
      that synergizes with volasertib and down-regulation of survivin is likely the
      consequence of DNA damage induced by sepantronium. 

PMID- 24660104
TI  - UMMS-4 enhanced sensitivity of chemotherapeutic agents to ABCB1-overexpressing
      cells via inhibiting function of ABCB1 transporter.
AB  - Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters
      through efflux of antineoplastic agents from cancer cells is a major obstacle to
      successful cancer chemotherapy. The inhibition of these ABC transporters is thus
      a logical approach to circumvent MDR. There has been intensive research effort to
      design and develop novel inhibitors for the ABC transporters to achieve this
      goal. In the present study, we evaluated the ability of UMMS-4 to modulate P
      glycoprotein (P-gp/ABCB1)-, breast cancer resistance protein (BCRP/ABCG2)- and
      multidrug resistance protein (MRP1/ABCC1)-mediated MDR in cancer cells. Our
      findings showed that UMMS-4, at non-cytotoxic concentrations, apparently
      circumvents resistance to ABCB1 substrate anticancer drugs in ABCB1
      overexpressing cells. When used at a concentration of 20 MUmol/L, UMMS-4 produced
      a 17.53-fold reversal of MDR, but showed no effect on the sensitivity of drug
      sensitive parental cells. UMMS-4, however, did not significantly alter the
      sensitivity of non-ABCB1 substrates in all cells and was unable to reverse ABCG2-
      and ABCC1-mediated MDR. Additionally, UMMS-4 profoundly inhibited the transport
      of rhodamine 123 (Rho 123) and doxorubicin (Dox) by the ABCB1 transporter.
      Furthermore, UMMS-4 did not alter the expression of ABCB1 at the mRNA and protein
      levels. In addition, the results of ATPase assays showed that UMMS-4 stimulated
      the ATPase activity of ABCB1. Taken together, we conclude that UMMS-4 antagonizes
      ABCB1-mediated MDR in cancer cells through direct inhibition of the drug efflux
      function of ABCB1. These findings may be useful for the development of safer and
      more effective MDR modulator. 

PMID- 24660105
TI  - Assessment of M867, a selective caspase-3 inhibitor, in an orthotopic mouse model
      for non-small cell lung carcinoma.
AB  - Radiation-induced lung injury (RILI) is a significant dose limiting complication
      of thoracic radiation for lung, breast, and esophageal cancer. Strategies for
      increasing the therapeutic index of radiation involve the use of radiosensitizing
      agents. We investigated the potential of M867 to sensitize non-small cell lung
      cancer (NSCLC) to radiation in vivo, while assessing its protective effects in
      normal lung parenchyma. H460-Luc2 cells were implanted into the mediastinum of
      athymic nude mice, which were separated into four treatment groups: control,
      M867, radiation therapy (RT) or combination. H460-Luc2 cell cultures were treated
      in parallel. Tumor growth was followed using bioluminescence imaging.
      Immunohistochemistry staining was used to detect phospho-Smad2/3 and cleaved
      caspase-3 expression. Western blot was done for the detection of cleaved caspase
      3 and phospho-Smad2/3. TUNEL assays were used to measure apoptosis. M867+RT group
      had significantly increased tumor growth inhibition relative to either treatment
      alone (p=0.02). M867+RT was associated with increased levels of apoptosis
      (p<0.01), but combination treatment was associated with a decrease in caspase
      dependent apoptosis relative to RT alone (p<0.01). We found that this increase in
      apoptosis in the M867+RT group was due to caspase-independent cell death. Based
      on early biomarker analyses of phospho-Smad 2/3 and cleaved caspase-3, M867+RT
      had a radio-protective effect on normal lung parenchyma. M867 may increase the
      therapeutic ratio of RT by enhancing the radiosensitivity of NSCLC while
      mitigating RILI. Further research is warranted to examine the late effects of
      lung injury and to study differences in the mechanism of action of M867 on lung
      cancer and normal tissue. 

PMID- 24660101
TI  - S100 protein family in human cancer.
AB  - S100 protein family has been implicated in multiple stages of tumorigenesis and
      progression. Among the S100 genes, 22 are clustered at chromosome locus 1q21, a
      region frequently rearranged in cancers. S100 protein possesses a wide range of
      intracellular and extracellular functions such as regulation of calcium
      homeostasis, cell proliferation, apoptosis, cell invasion and motility,
      cytoskeleton interactions, protein phosphorylation, regulation of transcriptional
      factors, autoimmunity, chemotaxis, inflammation and pluripotency. Many lines of
      evidence suggest that altered expression of S100 proteins was associated with
      tumor progression and prognosis. Therefore, S100 proteins might also represent
      potential tumor biomarkers and therapeutic targets. In this review, we summarize
      the evidence connecting S100 protein family and cancer and discuss the mechanisms
      by which S100 exerts its diverse functions. 

PMID- 24660106
TI  - Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse
      melanoma model.
AB  - Combination therapies for melanoma that target immune-regulatory networks are
      entering clinical practice, and more are under investigation in preclinical or
      clinical studies. Adenosine plays a key role in regulating melanoma progression.
      We investigated the effectiveness of cytotoxic T lymphocyte-associated antigen 4
      (CTLA-4) antibody (mAb) in combination with either modulators of adenosine
      receptors (AR) activation or an inhibitor of adenosine production in a murine
      model of melanoma. We found that treatment with APCP, selective inhibitor of the
      adenosine-generating nucleotidase CD73, enhanced the activity of anti-CTLA4 mAb,
      by improving tumor immune response. Blockade of the adenosine A2a receptor
      (A2aR), which plays a critical role in the regulation of T-cell functions,
      significantly reduced melanoma growth. Most importantly, combination therapy
      including an A2aR antagonist with anti-CTLA4 mAb markedly inhibited tumor growth
      and enhanced anti-tumor immune responses. Targeting A3R and CTLA4 was not as
      effective in limiting melanoma growth as targeting A2aR. These data suggest that
      the efficacy of anti-CTLA4 melanoma therapy may be improved by targeting multiple
      mechanisms of immune suppression within tumor tissue, including CD73 or A2a
      receptor. 

PMID- 24660107
TI  - GNG2 inhibits invasion of human malignant melanoma cells with decreased FAK
      activity.
AB  - It is well known that heterotrimeric G protein is composed of a Galpha-subunit
      and a Gbetagamma-dimer and promotes cancer characteristics. Our recent study
      showed reduced G protein gamma2 subunit (Gng2/GNG2) expression levels in
      malignant melanoma cells compared with those in benign melanocytic cells in both
      mice and humans. Our recent study also showed that reduced GNG2 alone augmented
      proliferation of malignant melanoma cells. To our knowledge, however, there is no
      evidence showing an effect of Gng2/GNG2 alone on metastasis of any cancers
      including malignant melanoma. In his study, we first prepared GNG2-overexpressed
      SK-Mel28 human malignant melanoma cells, in which GNG2 protein expression level
      was undetectably low. Migration and invasion activities of the GNG2-overexpressed
      malignant melanoma cells were suppressed up to 1/10th, with decreased activity of
      focal adhesion kinase (FAK). We then found that the expression level of GNG2 in
      A375M, a highly metastatic cell line, was significantly lower than that in A375P,
      the parental cell line of A375M. We finally showed that knockdown of GNG2 alone
      in A375P cells enhanced migration and invasion with increased FAK activity. Taken
      together, our results suggest that overexpression of GNG2 alone inhibits
      metastasis in human malignant melanoma cells with decreased FAK activity. Thus,
      GNG2 might be a candidate of molecular targets of prevention and therapy for
      metastasis of malignant melanoma. 

PMID- 24660108
TI  - Significance of peripheral neutrophil-lymphocyte ratio among gastric cancer
      patients and construction of a treatment-predictive model: a study based on 1131
      cases.
AB  - Gastric cancer (GC) is one of the most common and deadly malignancies nowadays,
      and inflammatory cells are closely related to tumor progression. This prospective
      study aims to uncover clinical significance of peripheral immune cells and build
      a treatment-predictive model. From July 2006 to July 2011, a total of 1131 GC
      patients were selected, with their general characteristics, peripheral blood and
      pathological parameters, and operational information obtained. The relevancies
      between preoperational neutrophil-lymphocyte ratio (NLR) and postsurgical
      pathological indexes were analyzed. SPSS 17.0 was applied in data analysis,
      comparing the differences of NLR between different groups using Mann-Whitney U
      test, contrasting the pathological differences between NLR elevated and reduced
      groups using Fisher test, and quantifying the correlation between post-surgical
      pathology and pre-operational NLR using univariate analysis. Patients were then
      classified into radical (applied in the training dataset) and non-radical
      gastrectomy (applied in the test dataset) groups, based on which we further tried
      to build a predictive model indicating appropriateness for radical resection
      using support vector machine (SVM). We found that: patients with tumor invading
      out of the myometrium (pT3-4) had significantly larger NLR than those with lesion
      limited within the myometrium (pT1-2) (P<0.05); poorly differentiated and
      undifferentiated malignancies were associated with higher NLR than well and
      moderately differentiated ones (P<0.05); there was larger NLR among patients with
      tumor length >=4 cm than those <4 cm (P<0.01); preoperative NLR was significantly
      positively correlated with tumor TNM classification, number of metastatic lymph
      nodes, invasive depth and tumor size (P<0.05); larger proportion of elevated NLR
      was significantly associated with larger tumor size, later tumor and nodal
      stages, and higher TNM classification (P<0.01). We finally built a SVM model
      based on peripheral carcinoembryonic antigen, carbohydrate antigen 19-9,
      lymphocyte percentage and platelet count, effectively predicting the
      inappropriateness of patients undergoing curative gastrectomy when all the 4
      parameters elevated with high accuracy (74.61% for the training dataset and
      75.28% for the test dataset). We concluded that peripheral blood NLR indicated
      tumor progression, and that an efficient treatment-predictive SVM model was
      constructed. 

PMID- 24660109
TI  - Vitamin C activation of the biosynthesis of epoxyeicosatrienoic acids.
AB  - The cardiovascular effects of vitamin C (VitC) could be mediated by
      epoxyeicosatrienoic acids (EETs). We aimed to study the mechanism of VitC
      dependent microsomal formation of cis- and trans-EETs and the regulation of EET
      levels in rat isolated perfused kidneys and in vivo. VitC biphasically stimulated
      rat kidney microsomal cis- and trans-EET formation in a ratio of 1:2, involving
      the participation of lipid hydroperoxides (LOOHs), Fe2+, and cytochrome P450
      (CYP). Levels of LOOHs correlated with microsomal EET production. LOOH
      stimulation of CYP isoforms resulted in preferred trans-over cis-EET formation
      from arachidonic acid and was associated with the cleavage of LOOHs, which
      indicated a CYP peroxygenase activity. EETs contributed to VitC-induced
      vasodilator responses in rat isolated perfused kidneys. VitC (1 mg/ml) given in
      the drinking water for 9 days doubled rat urinary EET excretion, increased plasma
      levels of EETs, mostly trans-EETs, by 40%, and reduced plasma levels of 20
      hydroxyeicosatetraenoic acid. Depletion of VitC in brain cortex and kidney
      tissues by more than 20- and 50-fold, respectively, in gulonolactone oxidase
      knockout mice was associated with mild increases in tissue EETs. These data
      suggest that LOOHs are a determinant factor for EET formation in vivo in which
      VitC exerts a key regulatory effect. VitC-activated CYP peroxygenase activity may
      represent a CYP interaction with lipoxygenases and cyclooxygenases to mediate the
      cardiovascular effects of VitC via formation of EETs.

PMID- 24660111
TI  - Effect of transplantation of human embryonic stem cell-derived neural progenitor
      cells on adult neurogenesis in aged hippocampus.
AB  - Adult neurogenesis occurs within the special microenvironment in the subgranular
      zone of the hippocampus and the subventricular zone of the lateral ventricle of
      the mammalian brain. The special microenvironment is known as neurogenic niches.
      Multiple cell types, including endothelial cells, astroglia, ependymal cells,
      immature progeny of neural stem cells, and mature neurons, comprise the
      neurogenic niche. Differentiation of embryonic stem cells towards the neural
      lineage results in the generation of different neuronal subtypes and non-neuronal
      cells (mainly astrocytes). Therefore, it is reasonable to hypothesize that
      transplantation of human embryonic stem cell-derived neural progenitor cells can
      be used to modify neurogenic niches for facilitating adult neurogenesis.
      Furthermore, if generated new neurons are functionally integrated into the
      existing circuits of the aged hippocampus, synaptic plasticity in the hippocampus
      and learning/memory functions in aged mice should be enhanced. In this article,
      we provide a comprehensive review of the concepts in the regulation of adult
      neurogenesis by neurogenic niches and discuss the molecular mechanisms underlying
      the effect of stem cell transplantation on adult neurogenesis in aged
      hippocampus. 

PMID- 24660112
TI  - Rapid isolation of integrin rich multipotent stem cell pool and reconstruction of
      mouse epidermis equivalent.
AB  - We describe here epidermis reconstruction using multipotent mouse epidermal stem
      cells (EpSCs) enriched from keratinocyte isolates exploting exclusively the stem
      cell-adhesive property. This method excluded flowcytometry and was swift. Percent
      enrichment was measured by the uptake of Propidium iodide and Hoechst-33342 dye
      using flowcytometry to determine EpSCs yield. The sorted cells were characterized
      by analysis of stem cell markers using immunocytochemistry and immunoblotting
      techniques. Epidermis was reconstructed using the identified seeding density of
      EpSCs and the airlift tissue culture. Histology of natural vs reconstructed
      mammalian epidermis was also compared. Results showed a radical improvement of
      near 99% in the yield of integrin overexpressing EpSCs. The enriched EpSCs tested
      positive for biomarkers namely cytokeratin K-15 and, K-14, p63, beta-1-integrin,
      CD34 and could be passaged for longer durations. Adhesion sorted cells
      reconstructed the epidermis. The process of tissue reconstruction was faster
      using the adhesion sorted cells than the FACS sorted EpSCs. The product
      bioengineered using multipotent EpSCs was histologically similar to normal
      epidermis. Features like strata basalae, spinosum, granulosum, and corneum were
      alike real epidermis. The reconstructed epidermis displayed normal homeostasis,
      which can be considered an approximating actual product for investigative
      dermatology, toxicology, therapeutic research, regenerative medicine, and tissue
      engineering. 

PMID- 24660110
TI  - Decellularized matrices for cardiovascular tissue engineering.
AB  - Cardiovascular disease (CVD) is one of the leading causes of death in the Western
      world. The replacement of damaged vessels and valves has been practiced since the
      1950's. Synthetic grafts, usually made of bio-inert materials, are long-lasting
      and mechanically relevant, but fail when it comes to "biointegration".
      Decellularized matrices, instead, can be considered biological grafts capable of
      stimulating in vivo migration and proliferation of endothelial cells (ECs),
      recruitment and differentiation of mural cells, finally, culminating in the
      formation of a biointegrated tissue. Decellularization protocols employ osmotic
      shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase
      treatments; most of them effectively eliminate the cellular component, but show
      limitations in preserving the native structure of the extracellular matrix (ECM).
      In this review, we examine the current state of the art relative to
      decellularization techniques and biological performance of decellularized heart,
      valves and big vessels. Furthermore, we focus on the relevance of ECM components,
      native and resulting from decellularization, in mediating in vivo host response
      and determining repair and regeneration, as opposed to graft corruption. 

PMID- 24660113
TI  - Phenotype-dependent role of the L-type calcium current in embryonic stem cell
      derived cardiomyocytes.
AB  - Although the L-type Ca(2+) current (ICa,L) plays an important role in cardiac
      contractility and pacemaking, its role in embryonic stem-cell derived
      cardiomyocytes (ESC-CMs) has not yet been explored in detail. We used patch-clamp
      techniques to characterize ICa,L, action potential properties, and nifedipine (an
      ICa,L blocker) sensitivity on spontaneously contracting embryoid bodies (EBs) or
      isolated ESC-CMs. Cellular preparations exhibited differential sensitivity to
      nifedipine, with substantial variation in the dose required to abolish
      automaticity. Isolated ESC-CMs expressing nodal-like action potentials were
      highly sensitive to nifedipine; 1 nM significantly decreased firing rate,
      diastolic depolarization rate (DDR), and upstroke velocity, and 10 nM completely
      abolished spontaneous activity. In contrast, ESC-CMs expressing atrial-like
      action potentials were relatively nifedipine-resistant, requiring 10 MUM to
      arrest automaticity; 1 MUM significantly decreased upstroke velocity while the
      firing rate and DDR were unaffected. Nodal-like cells exhibited a more negative
      voltage for half-maximal ICa activation (-30 +/- 1 mV vs. -20 +/- 3 mV; p<0.05)
      and slower inactivation (71 +/- 10 ms vs. 43 +/- 3 ms; p<0.05) than atrial-like
      cells. Our data indicate that ICa,L differentially regulates automaticity and
      chronotropy in nodal-like ESC-CMs, and primarily links excitation to contraction
      in atrial-like ESC-CMs by contributing to the upstroke phase of the action
      potential. 

PMID- 24660114
TI  - Non-Alcoholic Fatty Liver Disease: Current Perspectives and Future Direction in
      Disease pathogenesis, Treatment and Diagnosis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver
      diseases in the world. An important implication of this disease is the
      progression of the disease to a more complicated condition called non-alcoholic
      steatohepatitis (NASH) and the wide variety of clinical presentations. Over the
      past 5 years, remarkable progresses have been made in understanding the genetic
      basis for the disease. Recent clinical trials in pharmacotherapy for the disease
      have been encouraging as well. It is anticipated that the integration of the wide
      spectrum information retrieved from genomics, transcriptomics and proteomics
      studies conducted in NAFLD and NASH will mediate a better understanding of the
      disease pathogenesis and facilitate the postulation of disease pathobiology
      pathways. Genetic and biological markers identified from the omics studies may
      hold promise for diagnosis, personalized treatment, early prevention and new drug
      development.

PMID- 24660115
TI  - Monosodium Urate and Tumor Necrosis Factor-alpha Increase Apoptosis in Human
      Chondrocyte Cultures.
AB  - Monosodium urate and tumor necrosis factor-alpha, are two potent mediators of
      separate inflammatory response pathways in arthritic joints where inflammation
      may be accompanied by the loss of chondrocyte vitality via apoptosis. To address
      this possibility in vitro, chondrocyte cultures were employed to determine the
      extent to which monosodium urate and recombinant TNF-alpha altered the frequency
      of apoptotic chondrocytes. Apoptosis as a function of the activation of p38
      kinase, C-Jun-terminal kinase, signal transducer and activator of transcription-3
      and/or the activity of xanthine oxidase was also studied. Using normal human
      chondrocytes, monosodium urate or recombinant tumor necrosis factor-alpha
      increased the frequency of apoptosis and activity of xanthine oxidase. However,
      the xanthine oxidase-specific inhibitor, febuxostat, failed to blunt this
      response. Monosodium urate, tumor necrosis factor-alpha or the Janus kinase
      inhibitor, AG-490, increased the frequency of apoptotic nuclei in macroaggregate
      pellet cultures initiated from juvenile human chondrocytes, but not in pellet
      cultures derived from mesenchymal stem cells. In OA chondrocytes, activation of
      p38, C-Jun-NH2-kinase and signal transducer and activator of transcription-3
      preceded apoptosis. Activation of signal transducer and activator of
      transcription-3 also was seen in pellet cultures initiated from juvenile
      chondrocytes and MSCs incubated with MSU, recombinant tumor necrosis factor-alpha
      or febuxostat, but apoptosis was increased only in the pellet cultures derived
      from juvenile chondrocytes. Although AG-490 or the combination of AG-490 and
      febuxostat inhibited signal transducer and activator of transcription-3
      activation, apoptosis was unaffected. These results showed that recombinant tumor
      necrosis factor-alpha, monosodium urate and AG-490 increased apoptosis in normal
      human chondrocytes, OA chondrocytes and human juvenile chondrocyte pellet
      cultures, but not in chondrocyte pellet cultures initiated from MSCs. The
      increased frequency of apoptotic chondrocytes in response to recombinant tumor
      necrosis factor-alpha or monosodium urate was not dependent on either activation
      of STAT3 or the activity of XO.

PMID- 24660116
TI  - Predictors of Post-Infectious Chronic Fatigue Syndrome in Adolescents.
AB  - This study focused on identifying risk factors for adolescent post-infectious
      chronic fatigue syndrome (CFS), utilizing a prospective, nested case-control
      longitudinal design in which over 300 teenagers with Infectious Mononucleosis
      (IM) were identified through primary care sites and followed. Baseline variables
      that were gathered several months following IM, included autonomic symptoms, days
      in bed since IM, perceived stress, stressful life events, family stress,
      difficulty functioning and attending school, family stress and psychiatric
      disorders. A number of variables were predictors of post-infectious CFS at 6
      months; however, when autonomic symptoms were used as a control variable, only
      days spent in bed since mono was a significant predictor. Step-wise logistic
      regression findings indicated that baseline autonomic symptoms as well as days
      spent in bed since mono, which reflect the severity of illness, were the only
      significant predictors of those who met CFS criteria at 6 months.

PMID- 24660117
TI  - Chemerin regulation and role in host defense.
AB  - Chemerin is a widely distributed multifunctional secreted protein implicated in
      immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis,
      myogenesis, and glucose homeostasis. Chemerin message is regulated by nuclear
      receptor agonists, metabolic signaling proteins and intermediates, and
      proinflammatory cytokines. Following translation chemerin is secreted as an
      inactive pro-protein, and its secretion can be regulated depending on cell type.
      Chemerin bioactivity is largely dependent on carboxyl-terminal proteolytic
      processing and removal of inhibitory residues. Chemerin is abundant in human
      epidermis where it is well-placed to provide barrier protection. In host defense,
      chemerin plays dual roles as a broad spectrum antimicrobial protein and as a
      leukocyte attractant for macrophages, dendritic cells, and NK cells. Here we
      review the mechanisms underlying chemerin regulation and its function in host
      defense. 

PMID- 24660119
TI  - Tissue plasminogen activator and inflammation: from phenotype to signaling
      mechanisms.
AB  - In disease conditions, inflammatory cells, such as neutrophils, T cells, and
      monocytes/macrophages, are recruited in response to injury cues and express
      panoply of proinflammatory genes through a combination of transcription factors.
      Tissue plasminogen activator (tPA), a member of the serine protease family, has
      been shown to act as cytokine to activate profound receptor-mediated signaling
      events. In this review, we will discuss the role of tPA in inflammation in
      various models, and illuminate its signaling mechanisms underlying its modulation
      of inflammation. 

PMID- 24660118
TI  - Dust events, pulmonary diseases and immune system.
AB  - Incidences of sand storms have increased in recent years and there is evidence
      that these dusts can move across long distances. Sand dusts have different
      adverse effects on health, but one of the most important of them is pulmonary
      disease. After inhalation of dust, many dust particles are moved to the airways.
      Dust particles can be sensed by airways epithelial cells, activate macrophages,
      dendritic cells and innate immune cells and then initiate responses in various
      populations of specific immune cells such as T helper cells subsets (Th1, Th2,
      Th17), T cytotoxic cells and B cells. Initiation of inflammatory immune
      responses, activation of immune cells and releases of many cytokines, chemokines
      and other inflammatory molecules, have variable pathologic affects on lung in
      different respiratory diseases. Unfortunately control of desert dusts is more
      difficult than control of air pollution. For prevention and treatment of
      respiratory diseases that are caused by desert dusts, researchers need well
      designed epidemiological studies, combined with analysis of the precise
      composition of sand dusts, and the precise mechanisms of the immune responses.
      Recognizing the exact cellular and molecular immune mechanisms would be very
      useful to find new approaches for treatment of desert dust associated pulmonary
      diseases. 

PMID- 24660120
TI  - Kindlin-3 in the immune system.
AB  - Kindlin-3 is a member of the kindlin family of focal adhesion proteins which bind
      to integrin beta-chain cytoplasmic domains to regulate integrin function. In
      contrast to kindlin-1 and kindlin-2 proteins, kindlin-3 is expressed mainly in
      the hematopoietic system. Mutations in kindlin-3 result in the rare genetic
      disorder, leukocyte adhesion deficiency type III (LAD-III), which is
      characterized by bleeding and recurrent infections due to deficient beta1, beta2
      and beta3 integrin activation in platelets and leukocytes. Here, we review the
      role of kindlin-3 in integrin activation and in different immune cell functions. 

PMID- 24660121
TI  - Aberrant apoptotic machinery confers melanoma dual resistance to BRAF(V600E)
      inhibitor and immune effector cells: immunosensitization by a histone deacetylase
      inhibitor.
AB  - BRAF(V600E)-inhibitors (BRAFi; e.g., vemurafenib) and modern immune-based
      therapies such as PD-1/PD-L1 and CTLA-4 checkpoints blockade and adoptive cell
      transfer (ACT) have significantly improved the care of melanoma patients. Having
      these two effective (BRAFi and immunotherapy) therapies raises the question
      whether there is a rational biological basis for using them in combination. We
      developed an in vitro model to determine whether tumor resistance mechanisms to a
      small molecule inhibitor of a driver oncogene, and to cytotoxic T lymphocyte
      (CTL)- and natural killer (NK) cell-delivered apoptotic death signals were
      exclusive or intersecting. We generated melanoma sublines resistant to BRAFi
      vemurafenib and to CTL recognizing the MART-1 melanoma antigen. Vemurafenib
      resistant (VemR) sublines were cross-resistant to MART CTL and NK cells
      indicating that a common apoptotic pathway governing tumor response to both
      modalities was disrupted. Pretreatment of VemR melanomas with a histone
      deacetylase inhibitor (HDACi) restored sensitivity to MART CTL and NK apoptosis
      by skewing the apoptotic gene programs towards a proapoptotic phenotype. Our in
      vitro findings suggest that during the course of acquisition of BRAFi resistance,
      melanomas develop cross-resistance to CTL- and NK-killing. Further, aberrant
      apoptotic pathways, amenable by an FDA-approved chromatin remodeling drug,
      regulate tumor resistance mechanisms to immune effector cells. These results may
      provide rational molecular basis for further investigations to combine these
      therapies clinically. 

PMID- 24660122
TI  - Urinary tract infections in multiple sclerosis: under-diagnosed and under
      treated? A clinical audit at a large University Hospital.
AB  - Multiple sclerosis (MS) is a chronic demyelinating immune-mediated disease of the
      central nervous system. Infections have been implicated in different aspects of
      the disease such as induction of relapses and possibly, progression. Bladder
      dysfunction and associated urinary tract colonization (UTC) and infections (UTIs)
      are common in MS patients. UTIs can exacerbate neurological symptoms in MS,
      whilst high-dose steroid treatment of acute neurological worsening with
      concurrent untreated UTC may lead to unmasking of infection. This clinical audit
      was designed to investigate whether our institution is adhering to the National
      Institute for Health Care and Excellence (NICE) Clinical Guideline 148 for the
      management of patients with lower urinary tract symptoms due to neurogenic
      bladder dysfunction. We identified 21 patients with abnormal urine dipsticks out
      of 118 patients presenting at Nottingham University Hospitals for clinical review
      or for assessment of a relapse. Patients were asked about catheter status and the
      presence of any lower urinary tract symptoms. In all cases of relapse assessment,
      current practice at our institution had been to delay treatment with
      methylprednisolone (MP), pending the results of microbiology culture and
      sensitivity testing. If the patient was confirmed to have an infection, treatment
      with MP was delayed further awaiting completion of a course of antibiotics. We
      suggest that corticosteroid treatment need not be delayed but rather administered
      simultaneously with antibiotic treatment for the UTI, provided that the patient
      has no systemic symptoms of infection (e.g. fever, rigors, raised CRP). Patients
      must be educated and cautioned to contact their doctor in the event that systemic
      symptoms do develop during treatment. 

PMID- 24660123
TI  - Does ethnicity play a role in the dosing of warfarin in Hawai'i?
AB  - Warfarin is the most common anticoagulant prescribed and its metabolism has been
      linked to two specific genes, CYP2C9 and VKORC1. This study analyzed 113 patients
      from 4 different ethnic backgrounds (Asian, Native Hawaiian, Portuguese, and
      Caucasian) and investigated the association between the mean daily dose of
      warfarin and ethnicity. Caucasian patients required the highest mean daily dose
      of warfarin 4.4 mg/day while Asian patients required the lowest mean daily dose
      of warfarin 2.5 mg/day. Portuguese patients and Native Hawaiian patients required
      mean of 3.8 mg/day. All three groups required a significantly lower dose than
      Caucasians. When adjusted for weight in kilograms, Native Hawaiian patients
      required a dose of 4.3 * 10(-2) mg/kg, Portuguese 4.4 * 10(-2) mg/kg and Asians
      4.0 * 10(-2) mg/kg. These three populations had similar mean milligrams/kilogram
      dose requirements while Caucasians required a significantly higher dose of 5.3 *
      10(-2) mg/kg. This data suggests that ethnicity should be taken into
      consideration when dosing warfarin. 

PMID- 24660124
TI  - Third and fourth degree perineal injury after vaginal delivery: does race make a
      difference?
AB  - Severe perineal injury (third and fourth degree laceration) at the time of
      vaginal delivery increases the risk of fecal incontinence, chronic perineal pain,
      and dyspareunia.1-5 Studies suggest the prevalence of severe perineal injury may
      vary by racial group.6 The purpose of the current study was to examine rates of
      severe perineal injury in different Asian and Pacific Islander subgroups. A
      retrospective cohort study was performed among all patients who had a vaginal
      delivery at Queens Medical Center in Honolulu, Hawai'i between January 1, 2002
      and December 31, 2003. Demographic and health related variables were obtained for
      each participant. Maternal race/ethnicity (Japanese, Filipino, Chinese, other
      Asian, Part-Hawaiian/Hawaiian, Micronesian, other Pacific Islander, Caucasian,
      multiracial [non-Hawaiian], and other) was self-reported by the patient at the
      time admission. The significance of associations between racial/ethnic groups and
      demographic and health related variables was determined using chi-square tests
      for categorical variables and analysis of variance for continuous factors.
      Multiple logistic regression was performed to adjust for potential confounders
      when examining severe laceration rates. A total of 1842 subjects met inclusion
      criteria. The proportion of severe perineal lacerations did not differ
      significantly between racial groups. In the multiple logistic regression
      analysis, operative vaginal delivery was related to both race and severe perineal
      laceration. However, despite adjusting for this variable, race was not associated
      with an increased risk of having a severe laceration (P = .70). The results of
      this study indicate the risk of severe perineal laceration does not differ based
      on maternal race/ethnicity. 

PMID- 24660126
TI  - A case study of unusual etiology of anterior uveitis with ocular hypertension
      iris metastasis of primary lung adenocarcinoma.
AB  - This is a case of anterior uveitis in a 50 year-old man caused by lung
      adenocarcinoma metastasis to the iris. The patient was initially worked up for
      pneumonia and was discovered to have multiple lung lesions on computed tomography
      scan. Prior to discharge, the patient began complaining of ocular redness, pain,
      photophobia and decreased visual acuity. The patient was given an initial
      diagnosis of anterior uveitis with uveitic glaucoma, which was later confirmed to
      be secondary to lung adenocarcinoma metastasis to the iris. Metastasis to the
      iris is a particularly rare cause of anterior uveitis and may inadvertently be
      left out of a physician's differential diagnosis. This case illustrates a rare,
      but clinically important cause of anterior uveitis with intraocular hypertension,
      which should be considered in all cases of ocular redness and pain. 

PMID- 24660125
TI  - Increasing primary care physician support for and promotion of cancer clinical
      trials.
AB  - Only 2.5%-3% of adult cancer patients participate in cancer clinical trials, yet
      about 20% of cancer patients are medically eligible to participate. Research
      suggests that the primary care provider (PCP) can influence a patient's awareness
      of, and potentially, his or her decision to consider a clinical trial. To address
      low cancer clinical trial accrual rates, 'Imi Hale Native Hawaiian Cancer Network
      partnered with The Queen's Cancer Center to provide and evaluate education on
      clinical trials to Hawai'i PCPs. The educational materials were developed from a
      national curriculum and tailored to local audiences. Objectives of the curriculum
      were to educate PCPs about common myths (attitudinal barriers) around clinical
      trials and suggest ways that PCPs can introduce the concept of clinical trials to
      their patients with cancer or suspicion of cancer. The curriculum was tested on
      128 PCPs in 2012. Knowledge of the PCP's role and their willingness to mention
      clinical trials were measured through a post-test immediately following the
      presentation, which 74 (58%) PCPs completed. The post-test results suggested an
      increase in awareness among PCPs of their potential role in cancer clinical trial
      accrual, and an increase in PCP willingness to mention clinical trials to their
      patients with suspicion of cancer or diagnosed with cancer. Although findings
      suggest that this intervention is useful in increasing PCP receptivity to
      promoting cancer clinical trials, more research is needed to test if increased
      willingness results in increased accrual of cancer patients into clinical trials
      in Hawai'i. 

PMID- 24660127
TI  - Medical school hotline: the role of MD1 in the John A. Burns School of Medicine
      MD curriculum.

PMID- 24660128
TI  - Insights in public health: Strengthening the epidemiology workforce through
      mentorship: practicum and fellowship experiences in the Family Health Services
      Division at the Hawai'i Department of Health.
AB  - There are significant shortages in the public health workforce and it's expected
      to worsen. Efforts to reduce this shortage are varied and include building the
      workforce by increasing exposure of students and young professionals in applied
      public health experiences. Providing these experiences increases productivity,
      and may help alleviate some of the workforce shortages in public health. This
      article seeks to highlight the work done at the Family Health Services Division
      (FHSD) in the Hawai'i Department of Health over the past 6 and half years in
      working with students in epidemiology practicum and fellowship experiences. 

PMID- 24660131
TI  - The Frequency and Impact of Exposure to Potentially Traumatic Events Over the
      Life Course.
AB  - We examined the frequency and impact of exposure to potentially traumatic events
      among a nonclinical sample of older adults (n = 3,575), a population typically
      underrepresented in epidemiological research concerning the prevalence of
      traumatic events. Current PTSD symptom severity and the centrality of events to
      identity were assessed for events nominated as currently most distressing.
      Approximately 90% of participants experienced one or more potentially traumatic
      events. Events that occurred with greater frequency early in the life course were
      associated with more severe PTSD symptoms compared to events that occurred with
      greater frequency during later decades. Early life traumas, however, were not
      more central to identity. Results underscore the differential impact of traumatic
      events experienced throughout the life course. We conclude with suggestions for
      further research concerning mechanisms that promote the persistence of post
      traumatic stress related to early life traumas and empirical evaluation of
      psychotherapeutic treatments for older adults with PTSD.

PMID- 24660133
TI  - Seven New Drimane-Type Sesquiterpenoids from Cultures of Fungus Phellinus
      tuberculosus.
AB  - ABSTRACT: Seven new drimane-type sesquiterpennoids, phellinuins A-G (1-7),
      together with one known compound 3beta,11,12-trihydroxydrimene (8) were isolated
      from the cultures of mushroom Phellinus tuberculosus. Their structures were
      elucidated on the basis of NMR and MS spectroscopic data and by comparison with
      data reported in the literature.

PMID- 24660130
TI  - Dynamic Interactions Between Cancer Stem Cells And Their Stromal Partners.
AB  - The cancer stem cell (CSC) paradigm presumes the existence of self-renewing
      cancer cells capable of regenerating all tumor compartments and exhibiting stem
      cell-associated phenotypes. Recent interpretations of the CSC hypothesis envision
      stemness as a dynamic trait of tumor-initiating cells rather than a defined and
      unique cell type. Bidirectional crosstalk between the tumor microenvironment and
      the cancer bulk is well described in the literature and the tumor-associated
      stroma, vasculature and immune infiltrate have all been implicated as direct
      contributors to tumor development. These non-neoplastic cell types have also been
      shown to organize specific niches within the tumor bulk where they can control
      the intra-tumor CSC content and alter the fate of CSCs and tumor progenitors
      during tumorigenesis to acquire phenotypic features for invasion, metastasis and
      dormancy. Despite the complexity of the tumor-stroma interactome, novel
      therapeutic approaches envision combining tumor-ablative treatment with
      manipulation of the tumor microenvironment. We will review the currently
      available literature that provides clues about the complex cellular network that
      regulate the CSC phenotype and its niches during tumor progression.

PMID- 24660134
TI  - Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured
      by Imaging Flow Cytometry.
AB  - ABSTRACT: Gaining a full understanding of the mechanisms of action of natural
      products as therapeutic agents includes observing the effects of natural products
      on cellular morphology, because abnormal cellular morphology is an important
      aspect of cellular transformations that occur as part of disease states. In this
      study a set of natural products was examined in search of small molecules that
      influence the cylindrical morphology of fission yeast Schizosaccharomyces pombe.
      Imaging flow cytometry of large populations of S. pombe exposed to natural
      products captured cell images and revealed changes in mean length and aspect
      ratio of cells. Several natural products were found to alter S. pombe's
      morphology relative to control, in terms of elongating cells, shrinking them, or
      making them more round. These results may facilitate future investigations into
      methods by which cells establish and maintain specific shapes. GRAPHICAL
      ABSTRACT: Gaining a full understanding of the mechanisms of action of natural
      products as therapeutic agents includes observing the effects of natural products
      on cellular morphology, because abnormal cellular morphology is an important
      aspect of cellular transformations that occur as part of disease states. In this
      study a set of natural products was examined in search of small molecules that
      influence the cylindrical morphology of fission yeast Schizosaccharomyces pombe.
      Imaging flow cytometry of large populations of S. pombe exposed to natural
      products captured cell images and revealed changes in mean length and aspect
      ratio of cells. Several natural products were found to alter S. pombe's
      morphology relative to control, in terms of elongating cells, shrinking them, or
      making them more round. These results may facilitate future investigations into
      methods by which cells establish and maintain specific shapes.

PMID- 24660132
TI  - A bioactivity versus ethnobotanical survey of medicinal plants from Nigeria, west
      Africa.
AB  - Traditional medicinal practices play a key role in health care systems in
      countries with developing economies. The aim of this survey was to validate the
      use of traditional medicine within local Nigerian communities. In this review, we
      examine the ethnobotanical uses of selected plant species from the Nigerian flora
      and attempt to correlate the activities of the isolated bioactive principles with
      known uses of the plant species in African traditional medicine. Thirty-three
      (33) plant species were identified and about 100 out of the 120 compounds
      identified with these plants matched with the ethnobotanical uses of the plants. 

PMID- 24660135
TI  - Isolation of Microcystins from the Cyanobacterium Planktothrix rubescens Strain
      No80.
AB  - ABSTRACT: Three minor microcystins have been isolated from a Planktothrix
      rubescens strain. Their structures have been elucidated by one- and two
      dimensional NMR spectroscopy and high-resolution tandem mass spectrometry as the
      compounds [Asp(3),(E)-Dhb(7)]MC-LY (1), [Asp(3),(E)-Dhb(7)]MC-HtyW (2), and
      [Asp(3),(E)-Dhb(7)]MC-LW (3). The amino acids found at the variable positions 2
      and 4 of the microcystin core structure are in accordance with the predicted
      amino acid substrate activation selectivities of the non-ribosomal peptide
      synthetases McyA and McyB described earlier for this strain. All structural
      microcystin variants produced by this strain were shown to inhibit protein
      phosphatase 1 in the nanomolar range.

PMID- 24660136
TI  - New Taxane Diterpenoids from Taxus yunnanensis.
AB  - Three hitherto unknown taxane diterpenoids, namely baccatin VIII (1), baccatin IX
      (2), and baccatin X (3), along with 10 known analogues were isolated from an
      ethanolic extract of the twigs and leaves of Taxus yunnanensis. The new
      structures were characterized based on extensive spectroscopic analysis.
      Compounds 1 and 2 were tested for their in vitro cytotoxicity against five human
      tumor cell lines, and 1 exhibited inhibitory effects on HL-60 and MCF-7, with
      IC50 values of 3.44 and 9.67 MUM, respectively. 

PMID- 24660137
TI  - Diterpenoids and Limonoids from the Leaves and Twigs of Swietenia mahagoni.
AB  - Three new compounds, including two diterpenoids, nemoralisins H and I (1 and 2),
      and a limonoid, 2-methoxy khayseneganin E (3), along with four known constituents
      (4-7), were isolated from the leaves and twigs of Swietenia mahagoni. Their
      chemical structures were elucidated by means of spectroscopic analysis. The
      cytotoxities of these isolated constituents were assayed. 

PMID- 24660138
TI  - Crystal structures of the A2A adenosine receptor and their use in medicinal
      chemistry.
AB  - New insights into drug design are derived from the X-ray crystallographic
      structures of G protein-coupled receptors (GPCRs), and the adenosine receptors
      (ARs) are at the forefront of this effort. The 3D knowledge of receptor binding
      and activation promises to enable drug discovery for GPCRs in general, and
      specifically for the ARs. The predictability of modeling based on the X-ray
      structures of the A2AAR has been well demonstrated in the identification, design
      and modification of both known and novel AR agonists and antagonists. It is
      expected that structure-based design of drugs acting through ARs will provide new
      avenues to clinically useful agents.

PMID- 24660139
TI  - Nutrition, Exercise, and Wellness Treatment in bipolar disorder: proof of concept
      for a consolidated intervention.
AB  - BACKGROUND: This pilot study examines the proof of concept of a consolidated
      Nutrition, Exercise, and Wellness Treatment (NEW Tx) for overweight individuals
      with bipolar disorder. FINDINGS: Five participants completed NEW Tx, a 20-week
      individual cognitive behavioral therapy-based treatment comprising three modules:
      Nutrition teaches appropriate serving sizes and balanced diet; Exercise
      emphasizes increasing weekly physical activity; Wellness focuses on skills for
      healthy decision-making. Participants attended most sessions and reported high
      satisfaction with the treatment. Participants' weight, cholesterol and
      trigyclerides decreased over the study duration as well as number of daily
      calories and sugar intake. We found that weekly exercise duration more than
      tripled over the study duration and depressive symptoms and functioning have
      improved. CONCLUSIONS: These results offer proof of concept that consolidated NEW
      Tx is feasible and acceptable and has the potential to improve nutrition,
      exercise, wellness, and mood symptoms in bipolar disorder. Future iterations of
      NEW Tx will reflect the strengths and lessons learned from this study.

PMID- 24660141
TI  - Assimilation approach to measuring organizational change from pre- to post
      intervention.
AB  - AIM: To present a conceptual and measurement strategy that allows to objectively,
      sensitively evaluate intervention progress based on data of participants'
      perceptions of presenting problems. METHODS: We used as an example an
      organization development intervention at a United States Veterans Affairs medical
      center. Within a year, the intervention addressed the hospital's initially
      serious problems and multiple stakeholders (employees, management, union
      representatives) reported satisfaction with progress made. Traditional
      quantitative outcome measures, however, failed to capture the strong positive
      impact consistently reported by several types of stakeholders in qualitative
      interviews. To address the paradox, full interview data describing the medical
      center pre- and post- intervention were examined applying a validated theoretical
      framework from another discipline: Psychotherapy research. The Assimilation model
      is a clinical-developmental theory that describes empirically grounded change
      levels in problematic experiences, e.g., problems reported by participants. The
      model, measure Assimilation of Problematic Experiences Scale (APES), and rating
      procedure have been previously applied across various populations and problem
      types, mainly in clinical but also in non-clinical settings. We applied the APES
      to the transcribed qualitative data of intervention participants' interviews,
      using the method closely replicating prior assimilation research (the process
      whereby trained clinicians familiar with the Assimilation model work with full,
      transcribed interview data to assign the APES ratings). The APES ratings
      summarized levels of progress which was defined as participants' assimilation
      level of problematic experiences, and compared from pre- to post-intervention.
      RESULTS: The results were consistent with participants' own reported perceptions
      of the intervention impact. Increase in APES levels from pre- to post
      intervention suggested improvement, missed in the previous quantitative measures
      (the Maslach Burnout Inventory and the Work Environment Scale). The progress
      specifically consisted of participants' moving from the APES stages where the
      problematic experience was avoided, to the APES stages where awareness and
      attention to the problems were steadily sustained, although the problems were not
      yet fully processed or resolved. These results explain why the conventional
      outcome measures failed to reflect the intervention progress; they narrowly
      defined progress as resolution of the presenting problems and alleviation of
      symptomatic distress. In the Assimilation model, this definition only applies to
      a sub-segment of the change continuum, specifically the latest APES stages. The
      model defines progress as change in psychological processes used in response to
      the problem, i.e., a growing ability to deal with problematic issues non
      defensively, manifested differently depending on APES stages. At early stages,
      progress is an increased ability to face the problem rather than turning away. At
      later APES stages, progress involves naming, understanding and successfully
      addressing the problem. The assimilation approach provides a broader
      developmental context compared to exclusively symptom, problem-, or behavior-
      focused approaches that typically inform outcome measurement in interpersonally
      based interventions. In our data, this made the difference between reflecting
      (APES) vs missing (Maslach Burnout Inventory, Work Environment Scale) the pre
      post change that was strongly perceived by the intervention recipients.
      CONCLUSION: The results illustrated a working solution to the challenge of
      objectively evaluating progress in subjectively experienced problems. This
      approach informs measuring change in psychologically based interventions.

PMID- 24660140
TI  - Impact of living with bipolar patients: Making sense of caregivers' burden.
AB  - The aim of the present review was to examine objective and subjective burdens in
      primary caregivers (usually family members) of patients with bipolar disorder
      (BD) and to list which symptoms of the patients are considered more burdensome by
      the caregivers. In order to provide a critical review about caregiver's burden in
      patients with bipolar disorder, we performed a detailed PubMed, BioMedCentral,
      ISI Web of Science, PsycINFO, Elsevier Science Direct and Cochrane Library search
      to identify all papers and book chapters in English published during the period
      between 1963 and November 2011. The highest levels of distress were caused by the
      patient's behavior and the patient's role dysfunction (work, education and social
      relationships). Furthermore, the caregiving role compromises other social roles
      occupied by the caregiver, becoming part of the heavy social cost of bipolar
      affective disorder. There is a need to better understand caregivers' views and
      personal perceptions of the stresses and demands arising from caring for someone
      with BD in order to develop practical appropriate interventions and to improve
      the training of caregivers. 

PMID- 24660142
TI  - Pain location and intensity during the first week following coronary artery
      bypass graft surgery.
AB  - BACKGROUND: Despite the advances in pain control following surgery, data on the
      location and distribution of pain following coronary artery bypass grafting
      (CABG) are lacking. OBJECTIVES: This study was intended to investigate the
      location, distribution, and intensity of pain in patients undergoing CABG during
      their postoperative hospital stay from the operation to the end of the first
      postoperative week. Factors that could affect pain intensity and distribution
      were analyzed as well. PATIENTS AND METHODS: The present study was conducted on
      138 patients who underwent CABG surgery at Rajaei cardiovascular, Medical and
      Research Center during May and July 2011. Location and intensity of pain were
      assessed using numeric rating scale (NRS) over time: every six hours after the
      operation on the first day (T1-T4, respectively), and on two (POD2), three
      (POD3), and seven days after the operation (POD7). RESULTS: Among 138 patients
      assessed in the study, the greatest severity of pain was reported on T2, with the
      mean severity of 3.4, followed by POD2 with the mean severity of 2.9 (P < 0.01).
      The location of the surgical incision had the most severity of pain in all
      patients (P < 0.01). On the site of surgical incision, a negative correlation was
      seen between the age and the severity of pain on T1 (P = 0.03, r = -0.180). Women
      experienced more severe pain compared to men at POD7. A significant correlation
      was seen between the severity of pain on POD7 and body mass index (BMI) (P <
      0.01, r = 0.23). In patients who had the longer duration of cardiopulmonary
      bypass (CBD), the most pain intensity was reported on T1 (P < 0.01, r = 0.18). A
      significant correlation was seen on the pain intensity on T4 and chest tube
      drainage (P < 0.01, r = 0.24). The correlation between the pain severity pain and
      duration of admission in intensive care unit (ICU), was significant on T1 (P <
      0.05, r = 0.18), T4 (P < 0.01, r = 0.29), POD2 (P < 0.01, r = 0.35) and POD7 (P <
      0.05, r = 0.18). CONCLUSIONS: Following CABG, the most severity of pain was
      reported at surgical incision on time T2. Pain began to decrease from the third
      day following the operation. Age, sex and BMI along with operation-related
      factors such as duration of CBP or chest tube drainage may affect the pain
      pattern following CABG surgery.

PMID- 24660143
TI  - Effects of preoperative use of oral dextromethorphan on postoperative need for
      analgesics in patients with knee arthroscopy.
AB  - BACKGROUND: Studies have shown that N-methyl-D-aspartate receptor (NMIDA) plays
      an essential role in postoperative pain. It seems that use of NMDA receptor
      antagonists such as Dextromethorphan intensifies the analgesic effects of
      opioids. OBJECTIVES: In this study, we evaluated the effect of preoperative
      administration of Dextromethorphan on postoperative pain reduction. PATIENTS AND
      METHODS: This double blind randomized clinical trial was conducted on
      arthroscopic surgery candidates. Participants were randomly allocated to
      interventions and assigned to two groups of Dextromethorphan and placebo. In
      Dextromethorphan group, the patients received 1 mg/kg Dextromethorphan orally the
      night before the operation. Pain severity based on the visual analog scale (VAS)
      up to 16 hours postoperation, use of opioids, and the first request for
      analgesics were recorded postoperatively. RESULTS: A total of 112 patients in the
      Dextromethorphan (n = 54) and placebo groups (n = 58) were evaluated. No
      significant difference was detected between the two groups for age, sex or ASA.
      The mean amount of opioid consumption was significantly lower in patients who
      received Dextromethorphan (10.7 +/- 5.6 mg) compared to the placebo group (13.1
      +/- 5.6 mg), (P = 0.03). The mean time until the first opioid request in patients
      who received Dextromethorphan was longer than that in the placebo group (P =
      0.01). CONCLUSIONS: The study results demonstrated that preemptive use of
      Dextromethorphan reduced postoperative pain and opioid consumption.

PMID- 24660144
TI  - Perioperative management of acquired hemophilia a: a case report and review of
      literature.
AB  - INTRODUCTION: Acquired hemophilia A is a rare bleeding disorder with a high
      mortality rate. Diagnosis and treatment of this disorder can be very challenging
      to anesthesiologists because of lack of a personal or familial abnormal bleeding
      history. CASE PRESENTATION: We report a 60-year-old woman who presented to the
      operating room for an urgent fasciotomy. She was initially diagnosed to have
      compartment syndrome of her left upper extremity secondary to an expanding
      hematoma after multiple unsuccessful venipuncture attempts. After surgical
      intervention, she developed recurrent intramuscular hematomas, became severely
      anemic, and required surgical re-exploration and multiple blood product
      transfusions. Ultimately, she was found to have an elevated activated partial
      thromboplastin time (aPTT), very low FVIII activity, and high FVIII inhibitor
      titers consistent with the diagnosis of acquired hemophilia A. CONCLUSIONS:
      Treatment strategies in acquired hemophilia are based on two major objectives.
      During the acute stage, effective control of bleeding is critical. The ultimate
      therapeutic goal during the subacute phase is the elimination of the inhibitors
      targeting factor VIII. Here, we present this case and will review current
      literature regarding therapeutic approaches to this rare condition in the
      operating room setting and postoperative course.

PMID- 24660145
TI  - Effects of adding ketamine to fentanyl plus acetaminophen on postoperative pain
      by patient controlled analgesia in abdominal surgery.
AB  - BACKGROUND: Postoperative pain is one of the most important complications
      encountered after surgery. A number of options are available for treating pain
      following surgery. One of those options is the use of intravenous patient
      controlled analgesia (PCA). Ketamine is an anesthetic drug relieving pain with
      its NMDA receptor antagonistic effect. OBJECTIVES: This study is aiming at better
      pain management after abdominal surgery; the effects of adding ketamine to
      intravenous fentanyl plus acetaminophen PCA were evaluated. PATIENTS AND METHODS:
      In a double-blind randomized clinical trial 100 patients, ASA I or II, 20 - 60
      years old were divided into two groups. These patients were abdominal surgery
      candidates. In order to control postoperative pain in the control group an IV
      patient-control analgesia (PCA) containing fentanyl 10 MUg/mL plus acetaminophen
      10 mg/mL was instructed to be used for the patients, but the patients in ketamine
      group received ketamine 0.5 mg/mL plus control group PCA content. During the
      first 48 hours after surgery, ketamine patients were evaluated every 8 hours (at
      rest, while moving and coughing) to determine their pain scores using VAS scale,
      sedation score, additional analgesics, nausea and vomiting. RESULTS: There were
      no significant demographic differences between two groups. Pain scores (at rest,
      while moving and coughing) during the first 48 hours were not significantly
      different between two groups (P values = 0.361, 0.367 and 0.204, respectively).
      Nausea scores were significantly lower in the ketamine group (P = 0.026).
      CONCLUSIONS: The addition of ketamine to intravenous fentanyl plus acetaminophen
      PCA had not extra effects in relieving post abdominal surgery pain.

PMID- 24660146
TI  - Magnesium Can Decrease Postoperative Physiological Ileus and Postoperative Pain
      in Major non Laparoscopic Gastrointestinal Surgeries: A Randomized Controlled
      Trial.
AB  - BACKGROUND: Magnesium is an antagonist of (N-methyl D-Aspartate) NMDA receptor
      and its related canals, and may affect perceived pain. OBJECTIVES: The aim of
      this study was to evaluate the impact of intravenous magnesium on the hemodynamic
      parameters, analgesic consumption and ileus. PATIENTS AND METHODS: A randomized,
      double blind, placebo controlled study was performed. Thirty two patients of ASA
      I or II, scheduled for major gastrointestinal (GI) surgery, were divided into
      magnesium and control groups. Magnesium group received a bolus of 40 mg/kg of
      magnesium sulphate, followed by a continuous perfusion of 10 mg/kg/h for the
      intraoperative hours. Postoperative analgesia was ensured by Morphine patient
      controlled analgesia (PCA). The patients were evaluated by Intraoperative
      hemodynamic parameters, the postoperative pain by numeral rating scale (NRS), and
      the total dose of intraoperative and postoperative analgesic consumption.
      Postoperative hemodynamic, respiratory parameters, physiological gastrointestinal
      obstruction (ileus), and side effects were also recorded. RESULTS: The study
      included 14 males and 18 females. Age range of patients was 17 to 55 years old.
      The average age in the magnesium group was 41.33 +/- 10.06 years and45.13 +/-
      11.74 years in control group. Mean arterial pressure (MAP) of magnesium group
      decreased during the operation but increased in control group (P < 0.001), and
      systemic vascular resistance (SVR) of magnesium group decreased during the
      operation also (P < 0.02) but increased in control group. Postoperative
      cumulative Morphine consumption in magnesium group, was significantly in lower
      level (P = 0.026). For NRS, severe pain was significantly lower, in magnesium
      group, at all intervals of postoperative evaluations, but moderate and mild pain
      were not lower significantly. Duration of postoperative ileus was 2.3 +/- 0.5
      days in magnesium group, and 4.2 +/- 0.6 days in control group (P = 0.01).
      CONCLUSIONS: Intravenous magnesium reduces postoperative ileus, postoperative
      severe pain and intra/post operative analgesic requirements in patients after
      major GI surgery. No side effects of magnesium in these doses were seen, so it
      seems to be beneficial along with routine general anesthesia in major GI
      surgeries.

PMID- 24660147
TI  - Comparison between spinal and general anesthesia in percutaneous nephrolithotomy.
AB  - BACKGROUND: Hemodynamic stability and blood loss reduction are subjects to
      further consideration in patients undergoing percutaneous nephrolithotomy (PNCL).
      OBJECTIVES: This study compared the preference of spinal anaesthesia (SA) or
      general anaesthesia (GA) in respect to mentioned concerns. PATIENTS AND METHODS:
      In this randomized clinical trial, 59 patients who underwent PCNL divided into SA
      and GA groups. 15-20 mg from intra-thecal bupivacaine 0.5%, and premedication of
      0.01-0.02 mg from midazolam, were given to patients in SA group (n = 29).
      Patients in GA group (n = 30) received premedication of 1-2 ug/kg from fentanyl
      and 0.01-0.02 mg/kg from midazolam, and intravenously anaesthetized with 100
      ug/kg/min of propofol and 0.5 mg/kg of atracurium, given by continuous infusion
      and N2O/O2 50%. Mean arterial pressure (MAP) and heart rate were recorded intra
      operatively and during recovery. RESULTS: MAP and heart rate show no significant
      differences at designated time points between two groups (P > 0.05). Surgery
      time, anesthesia time, bleeding volume, and analgesic intake were significantly
      reduced in SA group (P < 0.05). CONCLUSIONS: It seems that, in patients
      undergoing PNCL, SA is as effective and safe as GA. Patients who undergo PNCL
      under SA require smaller amounts of analgesic dose and show hemodynamic stability
      during surgery and recovery time. Also, SA technique provides decreased blood
      loss and shortened surgery as well as anesthesia times compared to GA.

PMID- 24660148
TI  - Cardiac tamponade by hydatid pericardial cyst: a rare case report.
AB  - INTRODUCTION: Hydatid cysts are most commonly found in the liver and lungs but
      they are rarely found in pericardium. CASE PRESENTATION: We present a rare case
      of isolated hydatid cyst in pericardium of heart of a 70 year old female
      presented in casualty with unusual features like, dyspnea, palpitation and chest
      pain mimicking acute coronary syndrome. DISCUSSION: Hydatid cyst in Pericardium
      represents only 0.5-2% of cases of systemic echinoccocal infection. Isolated
      pericardial cyst is very rare in endemic region and may present mimicking acute
      coronary syndrome. Cardiac hydatid cysts should always be considered in presence
      of eosinophilia as present like acute coronary syndrome in endemic area.

PMID- 24660149
TI  - Treatment of advanced stage gonarthrosis with prolotherapy: case report.
AB  - INTRODUCTION: This case report aims to discuss the clinical and radiological
      outcomes of prolotherapy at a patient whom to total knee prosthesis had been
      planned but surgery couldn't be performed due to co-morbidities. CASE
      PRESENTATION: A 72 year old woman presented with severe pain at her knees for
      over 5 years. Treatment methods include weight loss, decreasing the weight
      bearing on the joint, stretching exercises, nonsteroid anti-inflammatory and
      steroid drugs, and physiotherapy. The Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) scale was applied to measure the osteoarthritis
      level of the patient: Pain level; 25 points, stiffness level; 10 points, Physical
      function loss; 80 points, and total WOMAC 115 points. At radiological evaluation,
      the patient was diagnosed as grade IV osteoarthritis due to significant
      osteophyte presence and complete joint space narrowing. Six sessions of knee
      prolotherapy protocol was applied to the patient, one session monthly.
      CONCLUSIONS: Significant improvement was noted at WOMAC scale (Pain level; 5
      points, stiffness level; 2 points, Physical function loss; 15 points, and total
      WOMAC 22 points). Osteoarthritis level of the patient was improved to grade I at
      radiological evaluation after a year. Our case is the report that presents
      radiological evidence in addition to clinical findings of improvement of
      osteoarthritis level. As a result of this case report, further studies aiming to
      offer a different minimally invasive treatment option to the patients before
      surgery may be performed. We are in the opinion that prolotherapy may be
      preferred more commonly as an efficient method once the importance of ligamentous
      structures at pathogenesis of osteoarthritis is established.

PMID- 24660150
TI  - Analgesic Efficacy of Diclofenac and Paracetamol vs. Meperidine in Cesarean
      Section.
AB  - BACKGROUND: One of the most important complications in cesarean surgery is
      postoperative pain, and different ways have been proposed to control it.
      OBJECTIVES: The purpose of this study was to determine the efficacy of Diclofenac
      and Paracetamol combination in comparison with Meperidine on postoperative pain
      after cesarean surgery. PATIENTS AND METHODS: One hundred and twenty women
      candidates for elective cesarean section under spinal anesthesia categorized as
      ASA class I were selected and randomly assigned to receive either Diclofenac
      suppository at the end of the operation and thereafter 1 gram infused bolus of
      Paracetamol (group A), or 20 mg bolus of Meperidine after transition to recovery
      room (group B) to control postoperative pain. RESULTS: Postoperative pain was
      present in recovery in 38.3% and 23.3% in groups B and A, respectively (P =
      0.009). Postoperative pain was seen after six hours of operation in 38.7% and
      16.7% in groups B and A, respectively (P = 0.010). Postoperative pain was present
      after 12 hours of operation in 38.3% and 15% in groups B and A, respectively (P =
      0.002). The additive Meperidine use was the same between the two groups in
      recovery (P > 0.05). The additive Meperidine use was seen after six hours of
      operation in 26.7% and 6.7% in groups B and A, respectively (P = 0.013). The
      additive Meperidine use was seen after 12 hours of operation in 16.7% and none of
      the patients in groups B and A, respectively (P = 0.004). The frequency of drug
      adverse effects was the same between the two groups (P > 0.05). CONCLUSIONS:
      Totally, according to the obtained results it may be concluded that Paracetamol
      and Diclofenac combination would have a better efficacy in postoperative pain
      control and need reduction to additive analgesia compared to Meperidine.

PMID- 24660151
TI  - Is fasting duration important in post adenotonsillectomy feeding time?
AB  - BACKGROUND: Adenotonsillectomy is a common otolaryngology surgery. Nausea and
      vomiting are the most common complications of this procedure with a prevalence
      ranging from 49% to 73 %. OBJECTIVES: Our aim was to evaluate the effects of
      short time fasting protocol on decreasing postoperative pain, nausea and
      vomiting, and initiation of oral feeding after adenotonsillectomy. PATIENTS AND
      METHODS: 120 children aged 4 to 14 years candidates for adenotonsillectomy were
      randomly divided into intervention and control groups (n = 120, 60 in each
      group). Each patient of the intervention group was given oral dextrose 10% as
      much volume as he could consume at 3 and 6 hours prior to the operation. All the
      data including pain severity, nausea and vomiting of the patients, the time of
      oral feeding initiation etc. were gathered in checklists after the operation.
      Statistical analyses were then performed using Statistical Package for the Social
      Sciences (SPSS) software version 16. Descriptive statistical methods and mean
      difference test for independent groups and chi square test or Fisher exact test,
      and if regression needed model test were applied. A P value of 0.05 or less was
      considered statistically significant. RESULTS: The amount of Acetaminophen
      administered for the intervention group was significantly lower than the control
      group, and also the time of oral feeding initiation was significantly shorter in
      the intervention group than the control group (P < 0.005). Pain severity at all
      occasions following surgery was significantly lower in the intervention group
      than the control group (P < 0.001). Although frequency of nausea at recovery time
      was significantly lower in the intervention group than the control group (P <
      0.002), there were no significant differences in frequency of nausea between the
      two groups at other postoperative occasions. Postoperative vomiting frequency was
      not significant between the two groups at any occasions. CONCLUSIONS: The
      findings of this survey showed that shortening the duration of pre
      adenotonsillectomy fasting period and hydration of patients several hours prior
      to the operation might be effective in decreasing postoperative pain and
      facilitating postoperative oral feeding initiation. Nevertheless this method does
      not seem to prevent postoperative nausea and vomiting.

PMID- 24660152
TI  - Magnesium sulfate and sufentanil for patient-controlled analgesia in orthopedic
      surgery.
AB  - BACKGROUND: Postoperative analgesia is one of the concerns of anesthesiologists
      and patients. Systemic opioid administration is the gold standard in reducing the
      severe pain after the surgery but some side effects prevent the use of adequate
      dosage of opioids. OBJECTIVES: The aim of this study was to evaluate the result
      of adding magnesium sulphate to sufentanil in patient-controlled intravenous
      analgesia (PCIA) system. PATIENTS AND METHODS: In this randomized clinical trial,
      60 patients candidate for lower limb orthopedic surgery were recruited in
      Poursina Medical Center for six months. They were randomly classified in two
      group of patient-controlled intravenous analgesia for postoperative pain control,
      one was group S [(sufentanil) (n = 30)] and the other was group S + M [(magnesium
      sulphate/sufentanil) (n = 30)]. The drug infusion rate was 5 mL/h. Each mL of
      solution in group S contained 1 mcg of sufentanil and in group M + S, 1 mcg of
      sufentanil and 200 mcg magnesium sulphate, respectively. Pain score, sedation
      score, satisfaction score, nausea and vomiting score were evaluated 6, 12, 24, 36
      and 48 hours after surgery. RESULTS: The demographic data between two groups were
      not significantly different. The pain scores after 6, 12 and 24 hours in S and S
      + M groups were significantly different. But the comparison of Visual Analogue
      Scale (VAS) scores after 36 and 48 hours didn't show significant differences (P <
      0.001). Comparison of the sedation, nausea and vomiting scores between two groups
      did not show any difference. But the number of patient's satisfaction in S + M
      group was more than S group which suggests significant differences (P < 0.05).
      CONCLUSIONS: This study showed that magnesium sulphate added to sufentanil
      through PCIA is an effective method to alleviate pain in patients undergoing
      lower limb orthopedic surgery. Moreover, we found fewer side effects on magnesium
      sufentanil regimen in terms of in nausea, vomiting, and sedation; and patients'
      satisfaction in this regimen was more rather than that in the regiment of
      sufentanil alone.

PMID- 24660153
TI  - A case of death caused by tracheal tube aspiration.
AB  - INTRODUCTION: Airway management, especially outside the operating room, needs
      meticulous observation in order to avoid certain risks, such as; endotracheal
      tube (ETT) disloca-tion, esophageal intubation, and unwanted extubation. ETT or
      tracheostomy dislocation is responsible for one-half of death or brain damage
      cases in the ICU. Despite appropri-ate fixation of an ETT, the previously
      mentioned compli-cations can still occur . A broken ETT and consequent airway
      obstruction may lead to lethal complications. CASE PRESENTATION: We report a case
      of death caused by tracheal tube aspiration, where it was located distal to the
      vocal cords, with a part of it entering the right bronchus and the mediastinum,
      after tearing the right bronchus. DISCUSSION: The vigilance and experience of
      medical personnel in the ICU, appropriate IV sedation, and using a bite block are
      the best ways to prevent mortality caused by aspiration of an ETT in all
      intubated patients.

PMID- 24660154
TI  - Comparing the duration of the analgesic effects of intravenous and rectal
      acetaminophen following tonsillectomy in children.
AB  - BACKGROUND: Postoperative pain control (especially, after adenotonsillectomy) has
      a very important effect on recovery time, hospitalization duration, hemodynamic
      disorders, bleeding, nausea, vomiting and medical costs. OBJECTIVES: The aim of
      this study was to investigate and compare the effects of intravenous and rectal
      acetaminophen on controlling post-adenotonsillectomy pain in children, and
      duration of their analgesic effects. PATIENTS AND METHODS: In this randomized
      double-blinded clinical trial, 96 children aged 4 - 10 years old with ASA
      physical status I or II who were candidates for adenotonsillectomy surgery in
      Amir-al-Momenin Hospital, Rasht, Iran were entered into the study and randomly
      divided into two equal groups. Anesthesia in both groups was induced injecting
      fentanyl-thiopental and at racurium; afterwards is of lurane was used to maintain
      anesthesia. After anesthesia induction, one group received intravenous and the
      other one, rectal acetaminophen, and were later compared based on CHIPPS
      criteria. RESULTS: Data analysis indicated a significant relationship between
      reduction of postoperative pain and the use of intravenous or rectal
      acetaminophen (P = 0.0001); in group receiving IV acetaminophen, only 10.4% of
      patients had no pain whereas in group receiving rectal acetaminophen, this number
      reached 43.8%. Also, on 4 and 6 hour time intervals, pain in rectal acetaminophen
      receiving group was less than that in IV acetaminophen receiving group (P <
      0.05). Demand for additional analgesic medication in rectal acetaminophen
      receiving group was less than that in IV group (P = 0.0001). CONCLUSIONS: Post
      operative pain in rectal acetaminophen group was less than that in intravenous
      acetaminophen group, and rectal acetaminophen group demanded their first
      additional analgesic medication later.

PMID- 24660155
TI  - Comparison between the effects of alfentanil, fentanyl and sufentanil on
      hemodynamic indices during rapid sequence intubation in the emergency department.
AB  - BACKGROUND: Laryngoscopy and tracheal intubation lead to the alteration of
      hemodynamic parameters, including blood pressure and heart rate, in traumatic
      patients who sustain rapid sequence intubation (RSI). Various drugs such as
      fentanyl, alfentanil and sufentanil have been used to modify these hemodynamic
      responses. OBJECTIVES: The aim of the present study is to compare the effects of
      fentanyl, sufentanil and alfentanil in trauma patients who require RSI in the
      emergency department (ED). PATIENTS AND METHODS: This was a randomized double
      blinded study conducted on 90 patients (18-65 years old, ASA I, II), who needed
      intubation following trauma. The patients were randomly divided into three
      groups, Group I, Group II and Group III, who have received alfentanil, fentanyl
      and sufentanil, respectively. Heart rate, blood pressure, saturation of
      peripheral oxygen and end-tidal carbon dioxide were measured 5 minutes before and
      3, 5 and 10 minutes after intubation, respectively. The changes of the
      hemodynamic parameters were compared in between groups. Data were analyzed by One
      way ANOVA, General Linear Model Repeated Measure and Mauchly's Sphericity Test. A
      P < 0.05 was considered statistically significant. RESULTS: There was no
      significant statistical difference among groups with respect to hemodynamic
      parameters. CONCLUSIONS: Alfentanil, fentanyl and sufentanil can be used safely
      as premedication drugs for trauma patients who need intubation.

PMID- 24660156
TI  - The analgesic efficacy of preoperative oral Ibuprofen and acetaminophen in
      children undergoing adenotonsillectomy: a randomized clinical trial.
AB  - BACKGROUND: Adenotonsillectomy is one of the most common surgical procedures in
      children. Several complications and morbidities are common after nasal surgeries
      and the most common is pain. Several techniques have been employed to reduce the
      severity of postoperative pain. One of the preoperative techniques is pre-emptive
      analgesia through preventive central hypersensitization. This technique is
      performed by applying analgesic methods before the onset of nociceptive stimuli,
      consequently decreasing postoperative analgesics requirements. OBJECTIVES:
      Preoperative oral drug administration for pain analgesia is performed in several
      methods. The aim of this study was to compare the analgesic effects of
      preoperatively administration of oral acetaminophen and ibuprofen. PATIENTS AND
      METHODS: In a double-blinded, randomized placebo-controlled study, sixty 4-12
      years old ASA I or II children scheduled for elective adenotonsillectomy, were
      assigned to receive either acetaminophen 15 mg/kg, ibuprofen 10 mg/kg or placebo
      30 minutes before the operation. Postoperative pain was assessed using the
      Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), upon arrival to the
      post anesthetic care unit (PACU) and ward. Findings were analyzed by SPSS version
      17 using variance analysis and Tukey's test. RESULTS: The average pain
      intensities were significantly lower in acetaminophen group based on the CHEOPS
      in both PACU and ward compared to ibuprofen or placebo groups; but there was no
      difference in pain intensity between the ibuprofen and placebo groups. Pain
      intensity in PACU in Acetaminophen group was 7.05 +/- 0.64 vs. 8.38 +/- 1.20 in
      placebo group and 8.14 +/- 0.85 in ibuprofen group, pain intensity in ward in the
      acetaminophen group was 6.0.87 +/- 0.85in the acetaminophen group, vs. 8.04 +/-
      1.02 in placebo group, and 7.78 +/- 0.78 in ibuprofen group. CONCLUSIONS: This
      study showed that administration of oral acetaminophen 30 minutes preoperatively,
      resulted in significantly lower pain intensity in children undergoing
      adenotonsillectomy in PACU and ward, compared to ibuprofen and placebo.

PMID- 24660157
TI  - Postoperative sore throat after laryngoscopy with macintosh or glide scope video
      laryngoscope blade in normal airway patients.
AB  - BACKGROUND: The Glide Scope videolaryngoscope provides a suitable view for
      intubation, with less force required. OBJECTIVES: The present study was
      conducted, to compare postoperative sore throat and hoarseness after laryngoscopy
      and intubation, by Macintosh blade or Glide Scope video laryngoscope in normal
      airway patients. PATIENTS AND METHODS: Three hundred patients were randomly
      allocated into two groups of 150: Macintosh blade laryngoscope or Glide Scope
      video laryngoscope. The patients were evaluated for 48 hours for sore throat and
      hoarseness by an interview. RESULTS: The incidence and severity of sore throat in
      the Glide Scope group, at 6, 24 and 48 hours after the operation, were
      significantly lower than in the Macintosh laryngoscope group. In addition, the
      incidence of hoarseness in the Glide Scope group, at 6 and 24 hours after the
      operation, were significantly lower than in the Macintosh laryngoscope group. The
      incidence and severity of sore throat in men, at 6 and 24 hours after the
      operation, were significantly lower than in the women. CONCLUSIONS: The incidence
      and severity of sore throat and hoarseness after tracheal intubation by Glide
      Scope were lower than in the Macintosh laryngoscope. The incidence and severity
      of sore throat were increased by intubation and longer operation times.

PMID- 24660158
TI  - Lidocaine and pain management in the emergency department: a review article.
AB  - CONTEXT: In the present review, the analgesic effects of lidocaine in acute or
      chronic painful conditions in the emergency department are discussed. Lidocaine,
      as a medium-acting local anesthetic with short onset time, is well-recognized,
      not only as a valuable medication for numerous neuropathic pain conditions, but
      also for the management of both acute and chronic pain. EVIDENCE ACQUISITION:
      Research studies related to the different applications of lidocaine in the
      emergency department were collected from different databases including Cochrane
      library, Medline (Ovid) and PubMed. The pooled data were categorized, summarized
      and finally compared. RESULTS: Our study revealed that lidocaine is broadly used
      in various therapeutic approaches for different types of pain, such as
      visceral/central pain, renal colic etc., in the emergency department.
      CONCLUSIONS: The antinociceptive properties of lidocaine are derived from
      multifaceted mechanisms, turning it into a medication that is safe to administer
      via different routes which makes it available for use in a variety of medical
      conditions.

PMID- 24660159
TI  - The effect of intravenous magnesium sulfate on laryngospasm after elective
      adenotonsillectomy surgery in children.
AB  - BACKGROUND: Laryngospasm is the protective reflex of tracheobronchial tree
      against secretions and hemorrhage. This reflex is more prevalent in
      adenotonsillectomy in the presence of light anesthesia, which can lead to
      obstruction of airway, complications, and mortality. Different methods have been
      studied for preventing this complication; however, none of them could reliably
      prevent it. OBJECTIVES: The objective was to assess the effect of magnesium
      sulfate on laryngospasm and coughing after adenotonsillectomy. PATIENTS AND
      METHODS: Seventy children with three to 12 years of age and ASA classes I and II,
      who were candidates for adenotonsillectomy, were recruited in this randomized
      clinical trial. The study group received 15 mg/kg intravenous magnesium sulfate
      and the control group received 0.9% normal saline with the same volume, 2 minutes
      after tracheal intubation via intravenous infusion for 20 minutes. After removing
      the endotracheal tube in the recovery room, the patients were assessed at minutes
      zero, 15, and 30in terms of laryngospasm and coughing. The assessment was based
      on four-point scale of severity of these complications and saturation percentage
      of arterial oxygen in operating and recovery room. After collecting the data,
      results were analyzed with the SPSS 16 software anda P value < 0.05 was
      considered statistically significant. RESULTS: Laryngospasm was not found in the
      magnesium sulfate group; however, its incidencewas5.7% in the control group. The
      incidence rates of coughs were 17.1% and 40% in the magnesium sulfate group and
      in the control group, respectively, which had no statistically significant
      differences. CONCLUSIONS: Intravenous magnesium sulfate with dose of 15 mg/kg
      could not prevent laryngospasm and coughing after removal of the endotracheal
      tube in patients undergoing adenotonsillectomy; however, it reduced coughing and
      laryngospasm in the magnesium sulfate group compared with the control group.

PMID- 24660160
TI  - A rare central venous catheter malposition: a case report.
AB  - INTRODUCTION: Central venous catheter placement is a routine procedure for the
      management of critically ill patients; however, it is important to ensure its
      proper placement. A central venous catheter malposition may cause various
      complications, some of which can be fatal. CASE PRESENTATION: We report an
      unexpected malposition of a catheter in the left internal jugular vein, where it
      entered into the left internal mammary vein. CONCLUSIONS: We think one of the
      influential factors for leading a guidewire and catheter into a nominated vein
      may be the left sided bevel of the needle at the time of internal jugular vein
      needle and catheter insertion. We were required to continue going towards the
      subclavian vein and accidentally turned into the left internal mammary vein.

PMID- 24660161
TI  - Robotic Anesthesia: How is it Going to Change Our Practice?

PMID- 24660162
TI  - Sedative efficacy of propofol in patients intubated/ventilated after coronary
      artery bypass graft surgery.
AB  - BACKGROUND: Sedation after open heart surgery is important in preventing stress
      on the heart. The unique sedative features of propofol prompted us to evaluate
      its potential clinical role in the sedation of post-CABG patients. OBJECTIVES: To
      compare propofol-based sedation to midazolam-based sedation after coronary artery
      bypass graft (CABG) surgery in the intensive care unit (ICU). PATIENTS AND
      METHODS: Fifty patients who were admitted to the ICU after CABG surgery was
      randomized into two groups to receive sedation with either midazolam or propofol
      infusions; and additional analgesia was administered if required. Inclusion
      criteria were as follows: patients 40-60 years old, hemodynamic stability,
      ejection fraction (EF) more than 40%; exclusion criteria included patients who
      required intra-aortic balloon pump or inotropic drugs post-bypass. The same
      protocol of anesthetic medications was used in both groups. Depth of sedation was
      monitored using the Ramsay sedation score (RSS). Invasive mean arterial pressure
      (MAP) and heart rate (HR), arterial blood gas (ABG) and ventilatory parameters
      were monitored continuously after the start of study drug and until the patients
      were extubated. RESULTS: The depth of sedation was almost the same in the two
      groups (RSS=4.5 in midazolam group vs 4.7 in propofol group; P = 0.259) but the
      total dose of fentanyl in the midazolam group was significantly more than the
      propofol group (12.5 mg/hr vs 4 mg/hr) (P = 0.0039). No significant differences
      were found in MAP (P = 0.51) and HR (P = 0.41) between the groups. The mean
      extubation time in patients sedated with propofol was shorter than those sedated
      with midazolam (102 +/- 27 min vs 245 +/- 42 min, respectively; P < 0.05) but the
      ICU discharge time was not shorter (47.5 hr vs 36.3 hr, respectively; P = 0.24).
      CONCLUSIONS: Propofol provided a safe and acceptable sedation for post-CABG
      surgical patients, significantly reduced the requirement for analgesics, and
      allowed for more rapid tracheal extubation than midazolam but did not result in
      earlier ICU discharge.

PMID- 24660163
TI  - Porcine epidemic diarrhea virus (PEDV) co-infection induced chlamydial
      persistence/stress does not require viral replication.
AB  - Chlamydiae may exist at the site of infection in an alternative replicative form,
      called the aberrant body (AB). ABs are produced during a viable but non
      infectious developmental state termed "persistence" or "chlamydial stress." As
      persistent/stressed chlamydiae: (i) may contribute to chronic inflammation
      observed in diseases like trachoma; and (ii) are more resistant to current anti
      chlamydial drugs of choice, it is critical to better understand this
      developmental stage. We previously demonstrated that porcine epidemic diarrhea
      virus (PEDV) co-infection induced Chlamydia pecorum persistence/stress in
      culture. One critical characteristic of persistence/stress is that the chlamydiae
      remain viable and can reenter the normal developmental cycle when the stressor is
      removed. Thus, we hypothesized that PEDV-induced persistence would be reversible
      if viral replication was inhibited. Therefore, we performed time course
      experiments in which Vero cells were C. pecorum/PEDV infected in the presence of
      cycloheximide (CHX), which inhibits viral but not chlamydial protein synthesis.
      CHX-exposure inhibited PEDV replication, but did not inhibit induction of C.
      pecorum persistence at 24 h post-PEDV infection, as indicated by AB formation and
      reduced production of infectious EBs. Interestingly, production of infectious EBs
      resumed when CHX-exposed, co-infected cells were incubated 48-72 h post-PEDV co
      infection. These data demonstrate that PEDV co-infection-induced chlamydial
      persistence/stress is reversible and suggest that this induction (i) does not
      require viral replication in host cells; and (ii) does not require de novo host
      or viral protein synthesis. These data also suggest that viral binding and/or
      entry may be required for this effect. Because the PEDV host cell receptor (CD13
      or aminopeptidase N) stimulates cellular signaling pathways in the absence of
      PEDV infection, we suspect that PEDV co-infection might alter CD13 function and
      induce the chlamydiae to enter the persistent state. 

PMID- 24660165
TI  - HIV-Related Knowledge and Perceptions by Academic Major: Implications for
      University Interventions.
AB  - Most universities offer human sexuality courses, although they are not required
      for graduation. While students in health-related majors may receive sexuality
      education in formal settings, majority of college students never receive formal
      sexual health or HIV/AIDS-related education, which may lead to elevated
      engagement in high-risk sexual behaviors. This study examines perceived knowledge
      about HIV/AIDS, perceived risk, and perceived consequences among college students
      by two distinct classifications of academic majors. Data were collected from 510
      college students. Binary and multinomial logistic regressions were performed to
      compare HIV-related covariates by academic major category. Limited differences
      were observed by science, technology, engineering, and mathematics
      categorization. Relative to health and kinesiology majors, those who self
      reported being "completely knowledgeable" about HIV were less likely to be
      physical sciences, mathematics, engineering, and business (PMEB) (OR = 0.41, P =
      0.047) or education, humanities, and social sciences majors (OR = 0.25, P =
      0.004). PMEB majors were less likely to report behavioral factors as a risk for
      contracting HIV (OR = 0.86, P = 0.004) and perceived acquiring HIV would be more
      detrimental to their quality of life (OR = 2.14, P = 0.012), but less detrimental
      to their mental well-being (OR = 0.58, P = 0.042). Findings can inform college
      wide campaigns and interventions to raise HIV/AIDS awareness and improve college
      health. 

PMID- 24660166
TI  - Cognitive Impairment and Medication Complexity in Community-Living Older Adults:
      The Health, Aging and Body Composition Study.
AB  - BACKGROUND: Medication complexity is a large determinant of adherence. Few
      studies have explored the relationship between cognitive impairment and
      medication complexity. OBJECTIVE: To evaluate whether cognitive impairment is
      associated with medication complexity for prescription and over-the-counter (OTC)
      medications. METHODS: In this cross-sectional analysis, we studied the
      association between cognitive impairment and the complexity of prescription and
      OTC drug regimens. Baseline participants were from the Health, Aging and Body
      Composition study, consisting of 3075 well-functioning 70- to 79-year-old black
      and white men and women. Cognitive impairment was defined by having a Modified
      Mini-Mental State Examination score <80. The complexity of prescription and OTC
      (including supplements/herbals) medications was assessed using a modified version
      of the Medication Regimen Complexity Index (mMRCI). The mMRCI score increases
      with complexity of dosage forms, number of medications, pill burden, and nondaily
      dosing. RESULTS: The mean (SD) age was 74 (2.9) years (n = 3055; 52% female, 41%
      black). The median prescription mMRCI score was 6 (range 0-66). The median OTC
      mMRCI score was 4 (range 0-71). Adjusting for health status, demographics, and
      access to care, medication complexity was lower in participants with cognitive
      impairment for prescription (adjusted RR 0.89; 95% CI 0.80 to 0.99) and OTC
      medications (adjusted RR 0.76; 95% CI 0.64 to 0.93) compared to those without
      cognitive impairment. The number of prescription medications was not different,
      but the number of OTC drugs was lower for those with cognitive impairment.
      CONCLUSIONS: In this cohort of well-functioning older adults, those with
      cognitive impairment had lower prescription complexity due to less-complex dosage
      forms, pill burden, or daily dosing. OTC complexity was also lower, primarily due
      to a lower number of OTC drugs. The results of this study show that further
      research on medication complexity and adherence and health outcomes in
      cognitively impaired individuals is warranted.

PMID- 24660167
TI  - Towards Effcient Label Fusion by Pre-Alignment of Training Data.
AB  - Label fusion is a multi-atlas segmentation approach that explicitly maintains and
      exploits the entire training dataset, rather than a parametric summary of it.
      Recent empirical evidence suggests that label fusion can achieve significantly
      better segmentation accuracy over classical parametric atlas methods that utilize
      a single coordinate frame. However, this performance gain typically comes at an
      increased computational cost due to the many pairwise registrations between the
      novel image and training images. In this work, we present a modified label fusion
      method that approximates these pairwise warps by first pre-registering the
      training images via a diffeomorphic groupwise registration algorithm. The novel
      image is then only registered once, to the template image that represents the
      average training subject. The pairwise spatial correspondences between the novel
      image and training images are then computed via concatenation of appropriate
      transformations. Our experiments on cardiac MR data suggest that this strategy
      for nonparametric segmentation dramatically improves computational efficiency,
      while producing segmentation results that are statistically indistinguishable
      from those obtained with regular label fusion. These results suggest that the key
      benefit of label fusion approaches is the underlying nonparametric inference
      algorithm, and not the multiple pairwise registrations.

PMID- 24660168
TI  - Molecular characterization of Capra hircus lysosomal alpha-mannosidase and
      potential mutant site for the therapy of locoweed poisoning.
AB  - Lysosomal alpha-Mannosidase (LAM) belongs to the glycoside hydrolyzing enzymes
      family 38 and is involved in the biosynthesis and turnover of N-linked
      glycoproteins process. Locoweeds, which contain swainsonine (SW) that inhibits
      LAM, are the main poisoning plants in many regions of the world, and thereby
      resulting in animal poisoning or even death. Based on regions of protein sequence
      conservation between LAM from Bos taurus and Homo sapiens, we cloned cDNA
      encoding Capra hircus LAM (chLAM). Expression of cDNA in Pichia pastoris resulted
      in the secretion of aLAM activity into the culture medium. The recombinant chLAM
      was activated 1.6 and 1.2-fold with Zn(2+) and Ca(2+), respectively. By homology
      modeling, molecular docking and mutant analysis, we obtained the probable binding
      modes of SW at the allosteric sites of chLAM, and the potential mutant sites for
      the resistance to SW. Prediction of SW sensitivity to A28 W/G, D58 Y/G mutant
      chLAM is lower than wild type chLAM. The obtained results lead to a better
      understanding of not only interactions between substrate/SW and chLAM, but also
      of a potential strategy for a novel therapy for locoweed poisoning. 

PMID- 24660164
TI  - Comparative review of Francisella tularensis and Francisella novicida.
AB  - Francisella tularensis is the causative agent of the acute disease tularemia. Due
      to its extreme infectivity and ability to cause disease upon inhalation, F.
      tularensis has been classified as a biothreat agent. Two subspecies of F.
      tularensis, tularensis and holarctica, are responsible for tularemia in humans.
      In comparison, the closely related species F. novicida very rarely causes human
      illness and cases that do occur are associated with patients who are immune
      compromised or have other underlying health problems. Virulence between F.
      tularensis and F. novicida also differs in laboratory animals. Despite this
      varying capacity to cause disease, the two species share ~97% nucleotide
      identity, with F. novicida commonly used as a laboratory surrogate for F.
      tularensis. As the F. novicida U112 strain is exempt from U.S. select agent
      regulations, research studies can be carried out in non-registered laboratories
      lacking specialized containment facilities required for work with virulent F.
      tularensis strains. This review is designed to highlight phenotypic (clinical,
      ecological, virulence, and pathogenic) and genomic differences between F.
      tularensis and F. novicida that warrant maintaining F. novicida and F. tularensis
      as separate species. Standardized nomenclature for F. novicida is critical for
      accurate interpretation of experimental results, limiting clinical confusion
      between F. novicida and F. tularensis and ensuring treatment efficacy studies
      utilize virulent F. tularensis strains. 

PMID- 24660169
TI  - A protocol for sonication-assisted Agrobacterium rhizogenes-mediated
      transformation of haploid and diploid sugar beet (Beta vulgaris L.) explants.
AB  - Hairy root cultures obtained after Agrobacterium rhizogenes-mediated genetic
      transformation can serve as a model system for studying plant metabolism and
      physiology, or can be utilized for the production of secondary metabolites. So
      far no efficient protocol of hairy root development in sugar beet has been
      publically released. In this work, two A. rhizogenes strains (A4T and LBA1334)
      carrying a binary vector pBIN-m-gfp5-ER or pCAMBIA1301 possessing gfp and uidA
      reporter genes were used to transform petiole explants of haploid and diploid
      sugar beet genotypes. Five treatment combinations of sonicated-assisted
      Agrobacterium-mediated transformation were compared. Hairy roots appeared on 0%
      to 54% of explants depending on the treatment combination used. The highest
      frequency was achieved when explants of a diploid genotype were sonicated for 15
      s in the inoculum containing A. rhizogenes of OD600=0.5 and then co-cultured for
      three days. Using the same treatment combinations the explants of haploid
      genotypes developed hairy roots with the frequency ranging from 10% to 36%.
      Transformation efficiency was independent on the bacterial strain used. The
      results indicate that haploid sugar beet explants are amenable to transformation
      using A. rhizogenes, and that the efficiency of that process can be increased by
      applying short ultrasound treatment. 

PMID- 24660171
TI  - Type II thioesterase ScoT is required for coelimycin production by the modular
      polyketide synthase Cpk of Streptomyces coelicolor A3(2).
AB  - Type II thioesterases were shown to maintain efficiency of modular type I
      polyketide synthases and nonribosomal peptide synthetases by removing acyl
      residues blocking extension modules. We found that thioesterase ScoT from
      Streptomyces coelicolor A3(2) is required for the production of the yellow
      pigmented coelimycin by the modular polyketide synthase Cpk. No production of
      coelimycin was observed in cultures of scoT disruption mutant. Polyketide
      production was restored upon complementation with an intact copy of the scoT
      gene. An enzymatic assay showed that ScoT thioesterase can hydrolyse a 12-carbon
      acyl chain but the activity is too low to play a role in product release from the
      polyketide synthase. We conclude that ScoT is an editing enzyme necessary to
      maintain the activity of polyketide synthase Cpk. We provide a HPLC based method
      to measure the amount of coelimycin P2 in a culture medium. 

PMID- 24660170
TI  - Response of the pea roots defense systems to the two-element combinations of
      metals (Cu, Zn, Cd, Pb).
AB  - The presence of the single metals (Cd, Pb, Cu, Zn) induces ROS (reactive oxygen
      species) production and causes oxidative stress in plants. While applied in two
      element combinations, trace metals impact organisms in a more complex way. To
      assess the resultant effect we treated the pea grown hydroponically with the
      trace metals in variants: CuPb, CuCd, CuZn, PbCd, ZnPb, ZnCd in concentrations of
      25 uM for each metal ion. Abiotic stress inhibited root elongation growth,
      decreased biomass production, induced changes in root colour and morphology. It
      changed rate of ROS production, malondialdehyde content, increased activity and
      altered gene expression of defence enzymes (superoxide dysmutase, catalase,
      ascorbate peroxidase, glutathione reductase, gamma-glutamylcysteine synthetase). 

PMID- 24660172
TI  - Frequencies of HLA-DQ2 and HLA-DQ8 haplotypes in Czech and Slovak coeliac
      patients and the healthy population.
AB  - Coeliac disease is an autoimmune disorder with genetic predisposition. The aim
      was to determine the frequency of HLA-DQ2 and HLA-DQ8 in Czech and Slovak
      patients and the healthy population. The study included 127 patients and 66
      healthy volunteers. HLA-DQ2 was identified in 85.03% patients, and 24.24% healthy
      individuals (P=0.0001; OR17.7632; CI=8.4347-37.4088). HLA-DQ8 was identified in
      11.81% patients and 15.5% healthy individuals. HLA-DQ8 occurred more often in HLA
      DQ2-negative patients compared to HLA-DQ2-positive patients (P=0.0494; OR3.5; CI
      1.0428-11.7468). At least one of the studied HLA-variants was found more often in
      patients than in healthy individuals (P=0.0001; OR58.8; CI 7.6856-449.8602). 

PMID- 24660173
TI  - Changes in the mitochondrial network during ectromelia virus infection of
      permissive L929 cells.
AB  - Mitochondria are extremely important organelles in the life of a cell. Recent
      studies indicate that mitochondria also play a fundamental role in the cellular
      innate immune mechanisms against viral infections. Moreover, mitochondria are
      able to alter their shape continuously through fusion and fission. These tightly
      regulated processes are activated or inhibited under physiological or
      pathological (e.g. viral infection) conditions to help restore homeostasis.
      However, many types of viruses, such as orthopoxviruses, have developed various
      strategies to evade the mitochondrial-mediated antiviral innate immune responses.
      Moreover, orthopoxviruses exploit the mitochondria for their survival. Such viral
      activity has been reported during vaccinia virus (VACV) infection. Our study
      shows that the Moscow strain of ectromelia virus (ECTV-MOS), an orthopoxvirus,
      alters the mitochondrial network in permissive L929 cells. Upon infection, the
      branching structure of the mitochondrial network collapses and becomes
      disorganized followed by destruction of mitochondrial tubules during the late
      stage of infection. Small, discrete mitochondria co-localize with progeny
      virions, close to the cell membrane. Furthermore, clustering of mitochondria is
      observed around viral factories, particularly between the nucleus and viroplasm.
      Our findings suggest that ECTV-MOS modulates mitochondrial cellular distribution
      during later stages of the replication cycle, probably enabling viral replication
      and/or assembly as well as transport of progeny virions inside the cell. However,
      this requires further investigation. 

PMID- 24660174
TI  - Surgical treatment of symptomatic accessory navicular in children and
      adolescents.
AB  - Although an accessory navicular (AN) is present in approximately 10% of the
      population, it rarely is symptomatic, and few cases necessitate operative
      intervention. When symptoms require surgical treatment, excision of the AN, with
      or without advancement of the posterior tibial tendon, usually is successful. We
      reviewed our records to evaluate the outcomes and complications of surgical
      treatment of AN. Retrospective chart review identified patients younger than 18
      who were treated surgically for a painful AN between 1991 and 2012. Medical
      records and digital images were reviewed to determine demographic information,
      duration of symptoms before surgery, type of AN, presence of flatfoot deformity,
      type of surgery, length of follow-up, outcomes, and complications. Twenty-seven
      patients (32 feet) had either isolated excision (14 feet) or excision plus tendon
      advancement (18 feet). Overall, 28 (87.5%) of feet had excellent or good
      functional outcomes. There was no significant difference in outcomes between the
      2 procedures, though there was a trend toward more complications and more
      reoperations after tendon advancement. 

PMID- 24660175
TI  - Use online coding discussion tools with caution.

PMID- 24660176
TI  - Is it safe to place a tibial intramedullary nail through a traumatic knee
      arthrotomy?
AB  - We conducted a study to compare postoperative infection and nonunion rates in
      tibial intramedullary nails (IMNs) placed through either uninjured knees or
      traumatic knee arthrotomies (KAs). We reviewed all adult tibial diaphyseal
      fractures (n = 1378) treated with an IMN between 1998 and 2010. Fourteen of these
      nails were placed through a traumatic KA. Each patient in the study group was
      assigned 4 separate matched controls for comparison. Controls were matched on
      age, sex, diabetes, smoking, and fracture classification (closed or open with
      Gustilo-Anderson). There were no postoperative infections (knee or fracture site)
      in the traumatic KA group and 2 (3.5%) in the control group (P = .473). One
      nonunion (7.1%) was noted in the traumatic KA group, and 9 (16%) were noted in
      the control group (P = .6694). To our knowledge, this is the first study to
      report outcomes of placing tibial IMNs through traumatic KAs. In our sample, the
      practice presented no increased risk either for infection (at the knee or the
      fracture site) or for nonunion with appropriate surgical debridement. 

PMID- 24660177
TI  - Endoprosthetic reconstruction after resection of musculoskeletal tumors.
AB  - In the literature, long-term survival of endoprosthetic reconstruction varies
      widely. Few long-term reports analyze both anatomical and disease-specific
      implant and patient survival. We retrospectively reviewed the results of 489
      patients who underwent resection of musculoskeletal tumor and reconstruction
      using an endoprosthetic device between December 1980 and August 2009. Implants
      were considered to have failed if the cemented components were revised for any
      reason, or the major body segment was removed for any reason. Implant survival,
      limb survival, and patient survival were determined using the Kaplan-Meier
      method. Sixty-one (12.5%) of the 489 cases were revised at a mean follow-up of
      6.6 years (range, 1 month to 27.3 years). Kaplan-Meier analysis revealed overall
      implant survival of 23.1% at 27 years (95% CI, 5.0% to 100.0%). At 15 years,
      modular implants outperformed older custom designs (90.8% and 59.6% survival,
      respectively; P < .05). Complications that led to failure of the limb-salvage
      effort included local recurrence (21 cases), infection (11), positive surgical
      margins (3), and intractable pain (1). Thirty-six amputations (7.4%) were
      performed. There were no cases of amputation performed as a direct outcome of
      mechanical failure. Endoprosthetic implants provide a reliable, durable method of
      reconstruction after resection of musculoskeletal tumors.

PMID- 24660178
TI  - Compared with magnetic resonance imaging, radiographs underestimate the magnitude
      of negative ulnar variance.
AB  - It is unclear how to interpret ulnar variance (UV) as determined by magnetic
      resonance imaging (MRI). Using a radiology database, we retrospectively assessed
      UV on MRI and compared it with UV on radiographs. MR images of 163 wrists (158
      patients) were reviewed. Mean (SD) UV was -0.16 (2.43) mm on radiographs, -0.62
      (2.41) mm on T1-weighted (bone-to-bone) MRI, and -0.50 (2.38) mm on gradient-
      echo or short tau inversion recovery (cartilage-to-cartilage) MRI. Compared with
      MRI, radiographs significantly underestimated the magnitude of negative UV. There
      was no difference in UV between different hand positions in MRI. Further research
      is needed to validate the measurement of UV on MRI and to determine its clinical
      utility.

PMID- 24660179
TI  - Allograft anterior cruciate ligament reconstruction in patients younger than 30
      years: a matched-pair comparison of bone-patellar tendon-bone and tibialis
      anterior.
AB  - We conducted a study to compare patient-reported outcomes and graft-rupture rates
      of bone-patellar tendon-bone (BPTB) and tibialis anterior (TA) allograft primary
      anterior cruciate ligament (ACL) reconstruction in patients younger than 30
      years. Patients were retrospectively identified as having undergone ACL
      reconstruction with either a BPTB (n = 20) or a TA (n = 20) allograft. Each
      patient in the BPTB group was matched to a patient in the TA group based on sex,
      age at time of surgery, height, weight, and preoperative activity level. The
      Lysholm Knee Scoring Scale and the International Knee Documentation Committee
      (IKDC) Subjective Knee Evaluation Form were administered at a minimum of 1 year
      after surgery. Mean Lysholm scores were 92.9 (BPTB) and 93.0 (TA), and mean IKDC
      scores were 92.6 (BPTB) and 90.3 (TA). The differences were not statistically
      significant. Overall graft-rupture rates for the study period were 4.7% (BPTB)
      and 1.9% (TA) (P = .18). There was no statistically significant difference in
      patient-rated outcomes and graft-rupture rates between BPTB and TA allografts for
      ACL reconstruction at a minimum of 1 year after surgery. Future research efforts
      should focus on mid- and long-term follow-up and objective outcomes. 

PMID- 24660180
TI  - The Metaizeau technique for pediatric radial neck fracture with elbow
      dislocation: intraoperative pitfalls and associated forearm compartment syndrome.
AB  - Displaced radial neck fractures in the pediatric population can be treated with
      retrograde intramedullary nailing of the radius (the Metaizeau technique). This
      method allows early movement, which may improve functional outcome.
      Unfortunately, repeated intraoperative attempts with this treatment in
      challenging fractures can result in compartment syndrome. In this article, we
      report the cases of 2 patients who underwent the Metaizeau technique for
      displaced radial neck fractures. In each case, optimal fixation of the radius was
      impossible because of concurrent elbow instability. Multiple attempts to reduce
      and stabilize these fractures may cause development or exacerbation of forearm
      compartment syndrome. The Metaizeau technique has been shown to be an effective
      method of minimally invasive surgical management of pediatric radial neck
      fractures. Its success may hinge on the ability of the elbow joint to hold the
      radial head in position while the implant is driven into the proximal radius in a
      retrograde fashion. Care should be used when dealing with radial neck fractures
      associated with elbow dislocation, as they may be difficult to reduce and
      stabilize. The increased operative time and soft-tissue injury associated with
      repeated attempts with this method may lead to or worsen compartment syndrome. 

PMID- 24660181
TI  - Occlusion of brachial pseudoaneurysm after periprosthetic humerus fracture.
AB  - Pseudoaneurysms of the brachial artery are rare and most often occur after a
      penetrating injury. The incidence of periprosthetic humerus fractures is low, and
      surgical treatment can be demanding. The treatment of choice for an occluded
      pseudoaneurysm of the brachial artery is saphenous vein bypass. In this article,
      we report the case of a 73-year-old woman who presented with an occluded
      pseudoaneurysm of the brachial artery sustained after a neglected periprosthetic
      humerus fracture. A saphenous vein bypass was performed after removal of the
      distal tip of the prosthesis. Patency was observed 3 months after surgery. This
      case shows malunion of a neglected periprosthetic humerus fracture and a good
      result after saphenous vein bypass. 

PMID- 24660182
TI  - Are academic orthopedic surgeons interested in global health?
AB  - Two thirds of the world's population lack orthopedic services. Natural disasters
      such as the 2010 Haiti earthquake temporarily increased volunteering, but the
      decision to volunteer regularly is likely multifactorial. In the study reported
      here, we investigated whether academic orthopedic surgeons are interested in
      volunteering abroad and identified factors that influence participation. Academic
      orthopedic surgeons were identified through the faculty listings of all 154
      orthopedic residency programs listed by the Association of American Medical
      Colleges (AAMC) Electronic Residency Application Service and were sent surveys by
      e-mail. Of the 3,697 eligible academic orthopedic surgeons, 600 were randomly
      selected, and 109 completed the survey. Of the 109 respondents, 52% had
      volunteered abroad previously, and 62% said they were highly likely to volunteer
      abroad in the future. The most common barriers were scheduling, and family and
      social commitments (65% and 66%, respectively), followed by lack of specialty
      specific opportunities (40%). In a multivariate model, the only barrier
      significantly decreasing likelihood to volunteer abroad was concern for medical
      safety (P = .015). Altruistic motivations (P = .005), religious sentiments (P =
      .006), international networking (P = .004), and fulfilling the true medical creed
      (P = .015) significantly increased likelihood. Academic orthopedic surgeons are
      interested in volunteering abroad. Addressing common motivations and barriers may
      help improve care in the developing world. 

PMID- 24660183
TI  - Using computed tomography to assess proximal humerus fractures.
AB  - Computed tomography (CT) scans are often used to evaluate proximal humerus
      fractures. We conducted a study to determine if use of preoperative CT scans
      affects surgical decision-making with respect to proximal humerus fractures.
      Three board-certified orthopedic surgeons interpreted plain radiographs of 40
      proximal humerus fractures and then CT scans with reformatted images. Results
      were assessed for interrater reliability. Use of CT significantly improved
      interobserver reliability in fracture characterization and assessment. Surgeons
      were more likely to identify a displaced fracture (P < .01), an impaction (P <
      .001), and involvement of the anatomical neck (P < .03). However, CT did not
      improve agreement with use of AO (Arbeitsgemeinschaft fur Osteosynthesefragen)
      fracture classification and did not significantly alter treatment
      recommendations. CT scans provide more detail about the character of proximal
      humerus fractures (displacement, involved segments) but do not significantly
      influence surgical treatment recommendations when compared with plain radiographs
      alone.

PMID- 24660184
TI  - Tip of the iceberg: subtle findings on traumatic knee radiographs portend
      significant injury.
AB  - Despite their low clinical yield, knee radiographs are among the most commonly
      acquired radiographic trauma studies in the emergency department. Although
      obvious fractures may be present, several subtler radiographic findings suggest
      internal derangement and significant injury. In this review, we provide an
      overview of traumatic knee radiography, including anatomy, acquisition
      techniques, and pitfalls with associated magnetic resonance imaging correlation
      when available. 

PMID- 24660185
TI  - Fracture of a dual-modular femoral component at the stem-sleeve junction in a
      metal-on-metal total hip arthroplasty.
AB  - Innovations in the design of dual-modular femoral components have afforded
      surgeons several intraoperative advantages during both primary and revision total
      hip arthroplasty (THA). Although use of these implants has become more popular,
      the long-term outcomes and potential complications of introducing a second
      modular junction are still to be determined. In addition, concerns about
      corrosion potentiation at modular junctions in metal-on-metal (MOM) THA have
      arisen in recent studies. In this article, we present a unique case of fracture
      at the modular junction of the stem and modular sleeve of a dual-modular femoral
      component implanted with a MOM articulation. The proposed mechanisms of failure,
      including crevice and fretting corrosion as well as the potential effect of metal
      debris generated by MOM articulations, are reviewed. This case report is the
      first to describe component fracture at the stem-sleeve junction of this modern
      generation dual-modular femoral component. Surgeons who encounter a painful dual
      modular femoral stem must entertain this mode of failure and consider junctional
      failure as a potential diagnosis for such a patient, particularly in the setting
      of a MOM articulation.

PMID- 24660186
TI  - Delayed spontaneous reduction of traumatic pediatric atlantoaxial rotatory
      subluxation.
AB  - Pediatric atlantoaxial rotatory subluxation (AARS) is a rare finding with various
      etiologies and treatment recommendations. Etiologies include both traumatic and
      nontraumatic causes. The diagnosis is suggested by clinical presentation and
      confirmed with imaging. Various forms of management have been discussed in the
      literature. However, no overall consensus has been established. We present 2
      pediatric cases showing delayed spontaneous reduction of traumatic AARS. Images
      from computed tomography (CT) were used for initial diagnosis and to track
      management progression. Although the subluxation persisted on the 1-month follow
      up CT in Case 1, the final CT images in both cases showed spontaneous reduction
      with anatomic positioning of C1 and C2. These cases demonstrate that delayed
      spontaneous reduction of traumatic pediatric AARS is possible with conservative
      treatment. Active reduction via traction may not be necessary. In the absence of
      compelling surgical indications to the contrary, a conservative approach to
      management of traumatic pediatric AARS is warranted.

PMID- 24660187
TI  - Horizontal ridge augmentation in conjunction with or prior to implant placement
      in the anterior maxilla: a systematic review.
AB  - PURPOSE: To systematically review clinical studies examining the survival and
      success rates of implants in horizontal ridge augmentation, either prior to or in
      conjunction with implant placement in the anterior maxilla. MATERIALS AND
      METHODS: A literature search was undertaken up to September 2012 including
      clinical studies in English with >= 10 consecutively treated patients and a mean
      follow-up of at least 12 months. Two reviewers screened the pertinent articles
      and extracted the data. Key words focused on the outcome parameters (implant
      success, implant survival, horizontal bone gain, and intra- and postoperative
      complications) in studies utilizing either a simultaneous approach (ridge
      augmentation performed at the time of implant placement) or a staged approach
      (ridge augmentation performed prior to implant placement) were analyzed. RESULTS:
      A total of 13 studies met the inclusion criteria, with 2 studies in the
      simultaneous group and 11 studies in the staged group. In the simultaneous group,
      survival rates of implants were 100% in both studies, with one study also
      reporting a 100% implant success rate. No data on horizontal bone gain were
      available. In the staged group, success rates of implants placed in horizontally
      augmented ridges ranged from 96.8% to 100% (two studies), and survival rates
      ranged from 93.5% to 100% (five studies). However, follow-up periods differed
      widely (up to 4.1 years). Mean horizontal bone gain determined at reentry
      (implant placement) ranged from 3.4 to 5.0 mm with large overall variations (0 to
      9.8 mm, five studies). Intraoperative complications were not reported.
      Postsurgical complications included mainly mucosal dehiscences (five studies),
      and, occasionally, complete failures of block grafts were described in one study.
      CONCLUSIONS: Staged and simultaneous augmentation procedures in the anterior
      maxilla are both associated with high implant success and survival rates. The
      level of evidence, however, is better for the staged approach than for the
      simultaneous one.

PMID- 24660188
TI  - Computer technology applications in surgical implant dentistry: a systematic
      review.
AB  - PURPOSE: To assess the literature on the accuracy and clinical performance of
      static computer-assisted implant surgery in implant dentistry. MATERIALS AND
      METHODS: Electronic and manual literature searches were applied to collect
      information about (1) the accuracy and (2) clinical performance of static
      computer-assisted implant systems. Meta-regression analysis was performed to
      summarize the accuracy studies. Failure/complication rates were investigated
      using a generalized linear mixed model for binary outcomes and a logit link to
      model implant failure rate. RESULTS: From 2,359 articles, 14 survival and 24
      accuracy studies were included in this systematic review. Nine different static
      image guidance systems were involved. The meta-analysis of the accuracy (24
      clinical and preclinical studies) revealed a total mean error of 1.12 mm (maximum
      of 4.5 mm) at the entry point measured in 1,530 implants and 1.39 mm at the apex
      (maximum of 7.1 mm) measured in 1,465 implants. For the 14 included survival
      studies (total of 1,941 implants) using static computer-assisted implant
      dentistry, the mean failure rate was 2.7% (0% to 10%) after an observation period
      of at least 12 months. In 36.4% of the treated cases, intraoperative or
      prosthetic complications were reported, which included: template fractures during
      the surgery, change of plan because of factors such as limited primary implant
      stability, need for additional grafting procedures, prosthetic screw loosening,
      prosthetic misfit, and prosthesis fracture. CONCLUSION: Different levels of
      quantity and quality of evidence were available for static computer-assisted
      implant placement, with tight-fitting high implant survival rates after only 12
      months of observation in different indications achieving a variable level of
      accuracy. Future long-term clinical data are necessary to identify clinical
      indications; detect accuracy; assess risk; and justify additional radiation
      doses, effort, and costs associated with computer-assisted implant surgery.

PMID- 24660189
TI  - Systematic review on success of narrow-diameter dental implants.
AB  - PURPOSE: The aim of this systematic review was to determine the survival and
      success rates of narrow-diameter implants (NDI) in different clinical indications
      compared to standard diameter implants. MATERIALS AND METHODS: Implant diameters
      were categorized into categories 1 (< 3.0 mm), 2 (3.00 to 3.25 mm), and 3 (3.30
      to 3.50 mm). Retro- and prospective studies with more than 10 patients and a
      follow-up time of 1 year or more were included. RESULTS: A literature search from
      1995 to 2012 revealed 10 articles reporting on implant diameters < 3 mm (Category
      1), 12 articles reporting on implant diameters 3 to 3.25 mm (Category 2), and 16
      articles reporting on implant diameters 3.3 to 3.5 mm (Category 3). The quality
      of the studies was mostly low with a high risk of bias. Dental implants < 3.0 mm
      (mini-implants) were one-piece in the edentulous arch and non-loaded frontal
      region with survival rates between 90.9% and 100%. For dental implants with a
      diameter between 3.0 and 3.25 mm, most were two-piece implants inserted into
      narrow tooth gaps without loading and in the frontal region. Survival rates for
      these implants ranged between 93.8% and 100%. Implants of 3.3 to 3.5 mm were two
      piece and were also used in the load-bearing posterior region. Survival rates
      were between 88.9% and 100%, and success rates ranged between 91.4% and 97.6%. A
      meta-analysis was conducted for NDI (3.3 to 3.5 mm), which showed no
      statistically significant difference in implant survival compared to conventional
      implants with an odds ratio of 1.16 (0.7 to 1.69). CONCLUSIONS: Narrow-diameter
      implants of 3.3 to 3.5 mm are well documented in all indications including load
      bearing posterior regions. Smaller implants of 3.0 to 3.25 mm in diameter are
      well documented only for single-tooth non-load-bearing regions. Mini-implants <
      3.0 mm in diameter are only documented for the edentulous arch and single-tooth
      non-load-bearing regions, and success rates are not available. Long-term follow
      up times > 1 year and information on patient specific risk factors (bruxism,
      restoration type) are also missing.

PMID- 24660190
TI  - Cone beam computed tomography in implant dentistry: a systematic review focusing
      on guidelines, indications, and radiation dose risks.
AB  - PURPOSE: The aim of the paper is to identify, review, analyze, and summarize
      available evidence in three areas on the use of cross-sectional imaging,
      specifically maxillofacial cone beam computed tomography (CBCT) in pre- and
      postoperative dental implant therapy: (1) Available clinical use guidelines, (2)
      indications and contraindications for use, and (3) assessment of associated
      radiation dose risk. MATERIALS AND METHODS: Three focused questions were
      developed to address the aims. A systematic literature review was performed using
      a PICO-based search strategy based on MeSH key words specific to each focused
      question of English-language publications indexed in the MEDLINE database
      retrospectively from October 31, 2012. These results were supplemented by a hand
      search and gray literature search. RESULTS: Twelve publications were identified
      providing guidelines for the use of cross-sectional radiography, particularly
      CBCT imaging, for the pre- and/or postoperative assessment of potential dental
      implant sites. The publications discovered by the PICO strategy (43 articles),
      hand (12), and gray literature searches (1) for the second focus question
      regarding indications and contraindications for CBCT use in implant dentistry
      were either cohort or case-controlled studies. For the third question on the
      assessment of associated radiation dose risk, a total of 22 articles were
      included. Publication characteristics and themes were summarized in tabular
      format. CONCLUSIONS: The reported indications for CBCT use in implant dentistry
      vary from preoperative analysis regarding specific anatomic considerations, site
      development using grafts, and computer-assisted treatment planning to
      postoperative evaluation focusing on complications due to damage of neurovascular
      structures. Effective doses for different CBCT devices exhibit a wide range with
      the lowest dose being almost 100 times less than the highest dose. Significant
      dose reduction can be achieved by adjusting operating parameters, including
      exposure factors and reducing the field of view (FOV) to the actual region of
      interest.

PMID- 24660191
TI  - Consensus statements and recommended clinical procedures regarding contemporary
      surgical and radiographic techniques in implant dentistry.

PMID- 24660192
TI  - Clinical performance of screw- versus cement-retained fixed implant-supported
      reconstructions--a systematic review.
AB  - PURPOSE: To assess the survival outcomes and reported complications of screw- and
      cement-retained fixed reconstructions supported on dental implants. MATERIALS AND
      METHODS: A Medline (PubMed), Embase, and Cochrane electronic database search from
      2000 to September 2012 using MeSH and free-text terms was conducted. Selected
      inclusion and exclusion criteria guided the search. All studies were first
      reviewed by abstract and subsequently by full-text reading by two examiners
      independently. Data were extracted by two examiners and statistically analyzed
      using a random effects Poisson regression. RESULTS: From 4,324 abstracts, 321
      full-text articles were reviewed. Seventy-three articles were found to qualify
      for inclusion. Five-year survival rates of 96.03% (95% confidence interval [CI]:
      93.85% to 97.43%) and 95.55% (95% CI: 92.96% to 97.19%) were calculated for
      cemented and screw-retained reconstructions, respectively (P = .69). Comparison
      of cement and screw retention showed no difference when grouped as single crowns
      (I-SC) (P = .10) or fixed partial dentures (I-FDP) (P = .49). The 5-year survival
      rate for screw-retained full-arch reconstructions was 96.71% (95% CI: 93.66% to
      98.31). All-ceramic reconstruction material exhibited a significantly higher
      failure rate than porcelain-fused-to-metal (PFM) in cemented reconstructions (P =
      .01) but not when comparing screw-retained reconstructions (P = .66). Technical
      and biologic complications demonstrating a statistically significant difference
      included loss of retention (P <= .01), abutment loosening (P <= .01), porcelain
      fracture and/or chipping (P = .02), presence of fistula/suppuration (P <= .001),
      total technical events (P = .03), and total biologic events (P = .02).
      CONCLUSIONS: Although no statistical difference was found between cement- and
      screw-retained reconstructions for survival or failure rates, screw-retained
      reconstructions exhibited fewer technical and biologic complications overall.
      There were no statistically significant differences between the failure rates of
      the different reconstruction types (I-SCs, I-FDPs, full-arch I-FDPs) or abutment
      materials (titanium, gold, ceramic). The failure rate of cemented reconstructions
      was not influenced by the choice of a specific cement, though cement type did
      influence loss of retention.

PMID- 24660193
TI  - Systematic review of the survival rate and incidence of biologic, technical, and
      esthetic complications of single implant abutments supporting fixed prostheses.
AB  - PURPOSE: To assess the 5-year survival rate and number of technical, biologic,
      and esthetic complications involving implant abutments. MATERIALS AND METHODS:
      Electronic (Medline) and hand searches were performed to assess studies on metal
      and ceramic implant abutments. Relevant data from a previous review were
      included. Two reviewers independently extracted the data. Failure and
      complication rates were analyzed, and estimates of 5-year survival proportions
      were calculated from the relationship between event rate and survival function.
      Multivariable robust Poisson regression was used to compare abutment
      characteristics. RESULTS: The search yielded 1,558 titles and 274 abstracts.
      Twenty-four studies were selected for data analysis. The survival rate for
      ceramic abutments was 97.5% (95% confidence interval [CI]): 89.6% to 99.4%) and
      97.6% (95% CI: 96.2% to 98.5%) for metal abutments. The overall 5-year rate for
      technical complications was 11.8% (95% CI: 8.5% to 16.3%), 8.9% (95% CI: 4.3% to
      17.7%) for ceramic and 12.0% (95% CI: 8.5% to 16.8%) for metal abutments.
      Biologic complications occurred with an overall rate of 6.4% (95% CI: 3.3% to
      12.0%), 10.4% (95% CI: 1.9% to 46.7%) for ceramic, and 6.1% (95% CI: 3.1% to
      12.0%) for metal abutments. CONCLUSIONS: The present meta-analysis on single
      implant prostheses presents high survival rates of single implants, abutments,
      and prostheses after 5 years of function. No differences were found for the
      survival and failure rates of ceramic and metal abutments. No significant
      differences were found for technical, biologic, and esthetic complications of
      internally and externally connected abutments.

PMID- 24660194
TI  - CAD/CAM technology for implant abutments, crowns, and superstructures.
AB  - PURPOSE: The aim of this systematic review was to compare implant prostheses
      fabricated by computer-assisted design and computer-assisted manufacturing
      (CAD/CAM) with conventionally fabricated implant prostheses when assessing
      esthetics, complications (biologic and mechanical), patient satisfaction, and
      economic factors. MATERIALS AND METHODS: Electronic searches for clinical studies
      focusing on long-term follow-up were performed using the PubMed and Ovid search
      engines. Concentrating on the restorative aspect of the CAD/CAM technology
      applicable to implant dentistry, pertinent literature was divided into articles
      related to implant abutments, crowns, and frameworks. RESULTS: A total of 18
      articles satisfied the inclusion criteria. Two articles reported on CAD/CAM
      crowns, six on abutments, and 10 on implant-supported CAD/CAM frameworks. The
      mean survival rate for CAD/CAM crowns was 98.85% and for CAD/CAM abutments 100%.
      The mean survival rate for CAD/CAM frameworks was 95.98%. CONCLUSION: Based on
      the current literature, CAD/CAM fabricated crowns, abutments, and frameworks
      demonstrate survival rates comparable to conventionally fabricated prostheses.
      Implant survival appears unaffected by fabrication technique. Since this
      technology encompasses several manufacturing variations, a new definition might
      be necessary to accurately define the processes under which the CAD/CAM
      restorations are fabricated. "Complete CAD/CAM product" where no or minimal
      manual intervention is employed could be a possible term.

PMID- 24660195
TI  - Consensus statements and recommended clinical procedures regarding restorative
      materials and techniques for implant dentistry.

PMID- 24660196
TI  - The influence of restorative procedures on esthetic outcomes in implant
      dentistry: a systematic review.
AB  - PURPOSE: The objectives of this review were to (1) identify if prosthodontic
      parameters influence the esthetic outcome of implant-supported restorations and
      (2) make clinically relevant recommendations based upon the findings. MATERIALS
      AND METHODS: Electronic and manual searches of dental literature were performed
      to collect information on esthetic outcomes based on objective criteria. The
      prosthodontic parameters included optimal three-dimensional implant position, the
      utilization of provisional restorations, the timing of provisional restoration
      with regard to implant placement, the choice of prosthodontic platform size and
      form, the abutment and definitive restoration material, and the mode of
      prosthesis retention. Regions including maxillary and mandibular anterior teeth
      and premolars were considered. All levels of evidence, including case studies,
      were accepted. RESULTS: From 472 titles, 152 full-text articles were evaluated
      and 58 records included for data extraction (15 randomized controlled trials, 6
      cohort studies, and 37 case series studies). Considerable heterogeneity in study
      design was found. A meta-analysis of controlled studies was not possible. It was
      consistently reported that facial malpositioning of implants increases the
      likelihood of mucosal recession. No studies directly compared esthetic outcomes
      associated with the use or non-use of provisional restorations. The literature
      contains a greater number of case series studies evaluating esthetic outcomes for
      protocols including, rather than excluding, provisional restorations. It is not
      possible to identify any significant variation in esthetic outcomes based on the
      character of the abutment platform from the current literature. Based on the
      findings, no significant difference can be established between all-ceramic and
      metal-ceramic prostheses with regard to esthetic indices over short observation
      periods. No firm conclusions relating esthetic benefits for cement in comparison
      to screw retention can be identified. CONCLUSIONS: There is a need for RCTs
      comparing accepted procedures in routine practice. The utilization of provisional
      restorations remains strongly recommended in order to trial the planned
      definitive restoration, to facilitate maturation of healing tissues and for
      patient convenience. Implant positioning according to the planned prosthesis
      remains a requirement to achieve a long-lasting esthetic outcome. The majority of
      studies reported on single-tooth replacement, and many of the outcomes may not be
      relevant or applicable to the large number of esthetic indications involving more
      than one tooth.

PMID- 24660198
TI  - Esthetic outcomes following immediate and early implant placement in the anterior
      maxilla--a systematic review.
AB  - PURPOSE: The objectives of this systematic review are (1) to quantitatively
      estimate the esthetic outcomes of implants placed in postextraction sites, and
      (2) to evaluate the influence of simultaneous bone augmentation procedures on
      these outcomes. MATERIALS AND METHODS: Electronic and manual searches of the
      dental literature were performed to collect information on esthetic outcomes
      based on objective criteria with implants placed after extraction of maxillary
      anterior and premolar teeth. All levels of evidence were accepted (case series
      studies required a minimum of 5 cases). RESULTS: From 1,686 titles, 114 full-text
      articles were evaluated and 50 records included for data extraction. The included
      studies reported on single-tooth implants adjacent to natural teeth, with no
      studies on multiple missing teeth identified (6 randomized controlled trials, 6
      cohort studies, 5 cross-sectional studies, and 33 case series studies).
      Considerable heterogeneity in study design was found. A meta-analysis of
      controlled studies was not possible. The available evidence suggests that
      esthetic outcomes, determined by esthetic indices (predominantly the pink
      esthetic score) and positional changes of the peri-implant mucosa, may be
      achieved for single-tooth implants placed after tooth extraction. Immediate (type
      1) implant placement, however, is associated with a greater variability in
      outcomes and a higher frequency of recession of > 1 mm of the midfacial mucosa
      (eight studies; range 9% to 41% and median 26% of sites, 1 to 3 years after
      placement) compared to early (type 2 and type 3) implant placement (2 studies; no
      sites with recession > 1 mm). In two retrospective studies of immediate (type 1)
      implant placement with bone graft, the facial bone wall was not detectable on
      cone beam CT in 36% and 57% of sites. These sites had more recession of the
      midfacial mucosa compared to sites with detectable facial bone. Two studies of
      early implant placement (types 2 and 3) combined with simultaneous bone
      augmentation with GBR (contour augmentation) demonstrated a high frequency (above
      90%) of facial bone wall visible on CBCT. Recent studies of immediate (type 1)
      placement imposed specific selection criteria, including thick tissue biotype and
      an intact facial socket wall, to reduce esthetic risk. There were no specific
      selection criteria for early (type 2 and type 3) implant placement. CONCLUSIONS:
      Acceptable esthetic outcomes may be achieved with implants placed after
      extraction of teeth in the maxillary anterior and premolar areas of the
      dentition. Recession of the midfacial mucosa is a risk with immediate (type 1)
      placement. Further research is needed to investigate the most suitable
      biomaterials to reconstruct the facial bone and the relationship between long
      term mucosal stability and presence/absence of the facial bone, the thickness of
      the facial bone, and the position of the facial bone crest.

PMID- 24660197
TI  - Soft tissue augmentation procedures for mucogingival defects in esthetic sites.
AB  - PURPOSE: This systematic review was performed to address the focus question: "In
      adult patients with soft tissue deficiencies around maxillary anterior implants,
      what is the effect on esthetic outcomes when a soft tissue procedure is
      performed?" In addition, this paper reviews the importance of presurgical
      esthetic risk assessment (ERA) starting with comprehensive team case planning
      prior to surgical intervention and a restorative-driven approach. MATERIALS AND
      METHODS: A thorough Medline database search performed on related MeSH terms
      yielded 1,532 titles and selected abstracts that were independently screened. Out
      of the 351 abstracts selected, 123 full-text articles were obtained for further
      evaluation. At each level, any disagreements were discussed until a consensus was
      reached. RESULTS: A total of 18 studies were included in this systematic review
      of esthetic outcomes following soft tissue procedures around implants with soft
      tissue deficiencies. A preliminary analysis of the included studies showed that
      the vast majority were case series studies with most not providing objective
      outcomes of their results. Moreover, only one randomized controlled trial was
      identified. Therefore, quantitative data analysis and subsequent meta-analysis
      could not be performed. The included studies were grouped according to the
      intervention on the peri-implant soft tissue performed and six groups were
      identified. The periodontal procedures performed around dental implants gave
      initial good results from the inflammation involved in wound healing, but in
      virtually all cases significant recession occurred as healing resolved and the
      tissues matured. CONCLUSIONS: Although success of implant therapy is similar in
      the anterior maxilla and other areas of the mouth, the majority of studies
      evaluating this therapy in the esthetic zone are lacking literature support, few
      in number, devoid of long-term follow-up and number of patients, and are subject
      to inclusion bias. The use of the ERA tool for all esthetic zone cases can
      benefit both the clinician and the patient to avoid any miscommunication and
      problems of expectation upon completion. All the available knowledge on this
      topic, including the approaches described in this paper, is based on a very
      limited literature support and thus should be addressed with caution. These
      concerns should encourage long-term good clinical trials for better assessment of
      those issues.

PMID- 24660199
TI  - Consensus statements and recommended clinical procedures regarding optimizing
      esthetic outcomes in implant dentistry.

PMID- 24660200
TI  - Loading protocols for single-implant crowns: a systematic review and meta
      analysis.
AB  - PURPOSE: To test whether or not immediate loading of single-implant crowns
      renders different results from early and conventional loading with respect to
      implant survival, marginal bone loss, stability of peri-implant soft tissue,
      esthetics, and patient satisfaction. MATERIALS AND METHODS: An electronic search
      of Medline and Embase databases including studies published prior to August 1,
      2012, was performed and complemented by a manual search. Randomized controlled
      trials (RCTs) comparing different loading protocols of single-implant crowns with
      a follow-up after restoration of at least 1 year were included. A meta-analysis
      yielded odds ratios (OR) and standardized mean differences (SMD) together with
      the corresponding 95% confidence intervals (95% CI). RESULTS: The search provided
      10 RCTs comparing immediate and conventional loading and 1 RCT comparing
      immediate and early loading. When assessing the implant survival at 1 year of
      loading, the meta-analysis of 10 studies found no significant differences between
      immediate and conventional loading (OR = 0.75; 95% CI: 0.32 to 1.76). The total
      difference of marginal bone loss during the first year of function between
      immediate and conventional loading protocols in 7 RCTs did not reach statistical
      significance (SMD = -0.05 mm; 95% CI: -0.41 to 0.31 mm). There were no
      significant differences between immediate and conventional loading regarding
      implant survival and marginal bone loss at 2, 3, and 5 years of loading. Three
      RCTs comparing the change of papilla level between immediate and conventional
      loading identified no significant differences. One study investigated the
      recession of the buccal mucosa after implant placement and found significantly
      inferior soft tissue loss for immediate loading as compared to conventional
      loading. Two RCTs investigated the recession of the buccal mucosa after insertion
      of the definitive crown and found no differences between immediate and
      conventional loading. The esthetics and the patient satisfaction were assessed in
      one and two RCTs, respectively. There were no significant differences between
      immediate and conventional loading. CONCLUSIONS: Immediately and conventionally
      loaded single-implant crowns are equally successful regarding implant survival
      and marginal bone loss. This conclusion is primarily derived from studies
      evaluating implants inserted with a torque >= 20 to 45 Ncm or an implant
      stability quotient (ISQ) >= 60 to 65 and with no need for simultaneous bone
      augmentation. Immediately and conventionally loaded implants do not appear to
      differently affect the papilla height during the first year of loading. Due to
      the heterogeneity of the time point of baseline measurements and contradictory
      findings in the studies, it is difficult to draw clear conclusions regarding the
      recession of the buccal mucosa. With respect to the assessment of esthetic
      outcomes and patient satisfaction, the data available remain inconclusive.

PMID- 24660201
TI  - Implant loading protocols for partially edentulous patients with extended
      edentulous sites--a systematic review and meta-analysis.
AB  - PURPOSE: The aim of this study was to systematically review the evidence for
      immediate implant loading in partially edentulous patients with extended
      edentulous sites and evaluate potential treatment modifiers. MATERIALS AND
      METHODS: An electronic search was performed in Medline, Embase, and Central to
      identify studies investigating the outcome of implants subjected to immediate
      loading (IL) (less than 1 week), early loading (EL) (1 week to 2 months), or
      conventional loading (CL) (more than 2 months) with implant-supported fixed
      dental prostheses (IFDPs) in partially edentulous patients with extended
      edentulous sites, ie, at least two adjacent teeth are missing. Only human studies
      with at least 10 cases and a minimum follow-up time of 12 months, reporting on
      solid-screw-type implants with rough surfaces and a diameter of at least 3 mm,
      were included. Weighted means of implant survival rates and risk ratios for
      implant survival at 1 year using meta-analytic tools were calculated to perform
      the following comparisons: IL vs EL, IL vs CL, and IL in the maxilla vs mandible.
      Noncomparative studies reporting on IL and EL protocols were summarized through
      descriptive methods. RESULTS: The search provided 3,872 titles, 837 abstracts,
      and 444 full-text articles. A total of 24 publications that comprised six
      comparative studies (five randomized controlled trials, one nonrandomized
      controlled trial) and 18 noncomparative studies were included for analysis. The
      comparison of weighted mean survival rates revealed no statistically significant
      difference between IL (97.9%) and EL (97.8%, P = .9405), and between IL (100%)
      and CL (99.3%, P = .3280). Meta-analysis showed no statistically significant
      difference in implant survival at 1 year between IL and EL (RR 0.90; 95% CI 0.30,
      2.70; P = .502). A meta-analysis comparing IL and CL could not be performed due
      to the low number of failures. No statistically significant difference was found
      for IL implants placed in the maxilla vs the mandible (RR 1.55; 95% CI 0.49,
      4.84; P > .05). Due to the small number of IL implants placed in the anterior, a
      comparison between implant survival in anterior vs posterior zones was not
      performed. Treatment modifiers were bone quality, primary stability, insertion
      torque, ISQ values, implant length, the need for substantial bone augmentation,
      the timing of implant placement, and the presence of parafunctional and smoking
      habits. CONCLUSIONS: IL presents similar implant survival rates as EL or CL for
      partially edentulous patients with extended edentulous sites in the posterior
      zone, as long as strict inclusion/exclusion criteria are followed. There is a
      lack of evidence for IL of multiple implants in the anterior zone of partially
      edentulous patients. Preliminary evidence suggests that IL may be equally
      successful in either the maxilla or mandible. Further research is needed before
      IL in partially edentulous patients with extended edentulous sites can be
      recommended in everyday practice.

PMID- 24660202
TI  - Implant loading protocols for edentulous patients with fixed prostheses: a
      systematic review and meta-analysis.
AB  - PURPOSE: To report on the effect of immediate implant loading with fixed
      prostheses compared to early and conventional loading on implant and prosthesis
      survival, failure, and complications. MATERIALS AND METHODS: An electronic and
      manual search was conducted to identify randomized controlled clinical trials
      (RCTs) as well as prospective and retrospective studies involving rough surface
      implants and implant fixed complete dental prostheses for edentulous patients.
      RESULTS: The 62 studies that fulfilled the inclusion criteria featured 4 RCTs, 2
      prospective case-control studies, 34 prospective cohort studies, and 22
      retrospective cohort studies. These studies yielded data from 2,695 patients
      (2,757 edentulous arches) with 13,653 implants. Studies were grouped according to
      the loading protocol applied; 45 studies reported on immediate loading, 8 on
      early loading, and 11 on conventional loading. For the immediate loading protocol
      with flap surgery, the implant and prosthesis survival rates ranged from 90.1% to
      100% and 93.75% to 100%, respectively (range of follow-up, 1 to 10 years). When
      immediate loading was combined with guided flapless implant placement, the
      implant survival rates ranged from 90% to 99.4%. For the early loading protocol,
      the implant and prosthesis survival rates ranged from 94.74% to 100% and 93.75%
      to 100%, respectively (range of follow-up, 1 to 10 years). For the conventional
      loading protocol, the implant and prosthesis survival rates ranged from 94.95% to
      100% and 87.5% to 100%, respectively (range of follow-up, 2 to 15 years). No
      difference was identified between maxilla and mandible. CONCLUSIONS: When
      selecting cases carefully and using dental implants with a rough surface,
      immediate loading with fixed prostheses in edentulous patients results in similar
      implant and prosthesis survival and failure rates as early and conventional
      loading. For immediate loading, most of the studies recommended a minimal
      insertion torque of 30 Ncm. The estimated 1-year implant survival was above 99%
      with all three loading protocols. Caution is necessary when interpreting these
      results, as there are many confounding factors that affect treatment outcomes
      with each of the loading protocols.

PMID- 24660203
TI  - Loading protocols for implant-supported overdentures in the edentulous jaw: a
      systematic review and meta-analysis.
AB  - PURPOSE: High survival rates have frequently been reported for immediately loaded
      implants. The aim of this systematic review was to compare immediately loaded
      with early and conventional loaded implants for overdenture treatment with regard
      to their 1-year survival rates. MATERIALS AND METHODS: Systematic database
      (Medline, Embase, CENTRAL) and hand searches were performed to identify
      prospective studies reporting on loading protocols for two-piece implants with
      micro-rough surfaces and diameters > 3 mm. Studies were grouped according to
      loading protocol, jaw, number of implants per jaw, and splinting. Meta-analyses
      of comparative reports were performed based on the calculated risk difference
      (RD). Descriptive analyses included the remainder prospective studies. Two
      investigators extracted the data independently. Kappa statistics served to
      evaluate the inter-investigator agreement. RESULTS: Of the 3,142 identified
      articles, 58 were included for data extraction. They comprised 11 studies
      comparing loading protocols as well as a further 47 prospective reports.
      Comparative studies were only available for mandibular overdentures. The meta
      analysis revealed a statistical tendency to support conventional over immediate
      loading (RD: -0.03, 95% confidence interval: -0.06, 0.00). The descriptive
      analysis of studies with lower evidence demonstrated partially contradictory
      findings. There, reported survival rates for immediately loaded implants lay
      between 81.6% and 100%, but depended on the number of implants placed. Most
      investigators preferred verifying an initial high insertion torque (>= 35 Ncm) or
      ISQ value (>= 60) before considering an implant for an immediate or early loading
      protocol. CONCLUSIONS: Although all three loading protocols provide high survival
      rates, early and conventional loading protocols are still better documented than
      immediate loading and seem to result in fewer implant failures during the first
      year. Only a few prospective case series are available to document immediate
      loading of implants supporting an overdenture in the edentulous maxilla.

PMID- 24660204
TI  - Consensus statements and clinical recommendations for implant loading protocols.

PMID- 24660205
TI  - The effects of anti-infective preventive measures on the occurrence of biologic
      implant complications and implant loss: a systematic review.
AB  - PURPOSE: To systematically appraise whether anti-infective protocols are
      effective in preventing biologic implant complications and implant loss after a
      mean observation period >= 10 years after loading. MATERIALS AND METHODS: An
      electronic search of Medline via PubMed and Embase via Ovid databases
      complemented by manual search was conducted up to October 31, 2012. Studies were
      included provided that they were published in English, German, French, or
      Italian, and conducted on >= 20 partially and fully edentulous patients with
      dental implants and regular (>= 1*/year) supportive periodontal therapy (SPT)
      over a mean observation period >= 10 years. Assessment of the identified studies
      and data extraction were performed independently by two reviewers. Authors were
      contacted if required. Collected data were reported by descriptive methods.
      RESULTS: The initial electronic search resulted in the identification of 994
      titles from Medline via PubMed and 531 titles from Embase via Ovid databases,
      respectively. After elimination of duplicate titles and exclusion of 60 full-text
      articles, 143 articles were analyzed, resulting in 15 studies eligible for
      qualitative analysis. The implant survival rate ranged from 85.7% to 99.2% after
      a mean observation period >= 10 years. One comparative study assessed the effects
      of regular SPT on the occurrence of biologic complications and implant loss.
      Overall, regular diagnosis and implementation of anti-infective therapeutic
      protocols were effective in the management of biological complications and
      prevention of implant loss. Residual probing depths at the end of active
      periodontal therapy and development of reinfection during supportive periodontal
      therapy (SPT) represented a significant risk for the onset of peri-implantitis
      and implant loss. Comparative studies indicated that implant survival and success
      rates were lower in periodontally compromised vs noncompromised patients.
      CONCLUSIONS: In order to achieve high long-term survival and success rates of
      dental implants and their restorations, enrollment in regular SPT including anti
      infective preventive measures should be implemented. Therapy of peri-implant
      mucositis should be considered as a preventive measure for the onset of peri
      implantitis. Completion of active periodontal therapy should precede implant
      placement in periodontally compromised patients.

PMID- 24660206
TI  - Improvements in implant dentistry over the last decade: comparison of survival
      and complication rates in older and newer publications.
AB  - PURPOSE: The objective of this systematic review was to assess and compare the
      survival and complication rates of implant-supported prostheses reported in
      studies published in the year 2000 and before, to those reported in studies
      published after the year 2000. MATERIALS AND METHODS: Three electronic searches
      complemented by manual searching were conducted to identify 139 prospective and
      retrospective studies on implant-supported prostheses. The included studies were
      divided in two groups: a group of 31 older studies published in the year 2000 or
      before, and a group of 108 newer studies published after the year 2000. Survival
      and complication rates were calculated using Poisson regression models, and
      multivariable robust Poisson regression was used to formally compare the outcomes
      of older and newer studies. RESULTS: The 5-year survival rate of implant
      supported prostheses was significantly increased in newer studies compared with
      older studies. The overall survival rate increased from 93.5% to 97.1%. The
      survival rate for cemented prostheses increased from 95.2% to 97.9%; for screw
      retained reconstruction, from 77.6% to 96.8%; for implant-supported single
      crowns, from 92.6% to 97.2%; and for implant-supported fixed dental prostheses
      (FDPs), from 93.5% to 96.4%. The incidence of esthetic complications decreased in
      more recent studies compared with older ones, but the incidence of biologic
      complications was similar. The results for technical complications were
      inconsistent. There was a significant reduction in abutment or screw loosening by
      implant-supported FDPs. On the other hand, the total number of technical
      complications and the incidence of fracture of the veneering material was
      significantly increased in the newer studies. To explain the increased rate of
      complications, minor complications are probably reported in more detail in the
      newer publications. CONCLUSIONS: The results of the present systematic review
      demonstrated a positive learning curve in implant dentistry, represented in
      higher survival rates and lower complication rates reported in more recent
      clinical studies. The incidence of esthetic, biologic, and technical
      complications, however, is still high. Hence, it is important to identify these
      complications and their etiology to make implant treatment even more predictable
      in the future.

PMID- 24660207
TI  - The therapy of peri-implantitis: a systematic review.
AB  - PURPOSE: To evaluate the success of treatments aimed at the resolution of peri
      implantitis in patients with osseointegrated implants. MATERIALS AND METHODS: The
      potentially relevant literature was assessed independently by two reviewers to
      identify case series and comparative studies describing the treatment of peri
      implantitis with a follow-up of at least 3 months. Medline, Embase, and The
      Cochrane Library were searched. For the purposes of this review, a composite
      criterion for successful treatment outcome was used which comprised implant
      survival with mean probing depth < 5 mm and no further bone loss. RESULTS: A
      total of 43 publications were included: 4 papers describing 3 nonsurgical case
      series, 13 papers describing 10 comparative studies of nonsurgical interventions,
      15 papers describing 14 surgical case series, and 11 papers describing 6
      comparative studies of surgical interventions. No trials comparing nonsurgical
      with surgical interventions were found. The length of follow-up varied from 3
      months to 7.5 years. Due to the heterogeneity of study designs, peri-implantitis
      case definitions, outcome variables, and reporting, no meta-analysis was
      performed. Eleven studies could be evaluated according to a composite success
      criterion. Successful treatment outcomes at 12 months were reported in 0% to 100%
      of patients treated in 9 studies and in 75% to 93% of implants treated in 2
      studies. Commonalities in treatment approaches between studies included (1) a
      pretreatment phase, (2) cause-related therapy, and (3) a maintenance care phase.
      CONCLUSIONS: While the available evidence does not allow any specific
      recommendations for the therapy of peri-implantitis, successful treatment
      outcomes at 12 months were reported in a majority of patients in 7 studies.
      Although favorable short-term outcomes were reported in many studies, lack of
      disease resolution as well as progression or recurrence of disease and implant
      loss despite treatment were also reported. The reported outcomes must be viewed
      in the context of the varied peri-implantitis case definitions and severity of
      disease included as well as the heterogeneity in study design, length of follow
      up, and exclusion/inclusion criteria.

PMID- 24660209
TI  - By the sweat of your brow.

PMID- 24660208
TI  - Consensus statements and clinical recommendations for prevention and management
      of biologic and technical implant complications.

PMID- 24660210
TI  - The Kent hospital Wound Recovery and Hyperbaric Medicine Center: a brief
      overview, 1998-2013.
AB  - A brief description of the Wound Recovery and Hyperbaric Medicine Center, now in
      its second decade of service, will inform the general medical community of this
      valuable asset. Demand for wound care services is predicted to grow steadily over
      the next several decades. Kent Hospital's vision for wound care is embodied in
      its thriving Wound Recovery and Hyperbaric Medicine Center. New cost- effective
      wound healing therapies must be developed and evidence-based practices
      established. New physicians and support staff must be trained. Only through a
      blending of high quality clinical care with research and education will these
      objectives be achieved and future successes in the management of patients and
      their wounds be made possible. 

PMID- 24660211
TI  - Successes and challenges to implementing an early childhood supplemental feeding
      program in rural Honduras: a qualitative study.
AB  - BACKGROUND: Malnutrition is a major cause of childhood illness, stunted growth
      and death worldwide. A supplemental nutrition program for young children was
      implemented in Guachipilincito, Honduras. This study explores early successes and
      challenges to implementing this program. METHODS: We conducted a qualitative,
      semi-structured, key informant interview study in 2012. Two researchers analyzed
      interview transcripts using the immersion/crystallization method of qualitative
      analysis. RESULTS: The program evolved from addressing macronutrient deficiency
      in 2010, to targeting micronutrient deficiency. Successes include: consistent
      food distribution, positive community feedback and establishment of a Honduran
      community oversight committee. Challenges include: tracking growth data, sharing
      of food among family members, and long-term sustainability. Next steps include:
      obtaining stable funding, utilizing local food suppliers, and increasing crop
      diversity. Participants identified cultural and economic factors contributing to
      challenges with these steps. CONCLUSION: While the feeding program is having
      successes, it still faces many challenges. Additional interviews with Honduran
      based staff, community leaders and program recipients may identify the best ways
      to address these challenges.

PMID- 24660212
TI  - Post-traumatic Raynaud's phenomenon following volar plate injury.
AB  - Post-traumatic Raynaud's phenomenon following non-penetrating or non-repetitive
      injury is rare. We report a case of Raynaud's phenomenon occurring in a single
      digit 3 months following volar plate avulsion injury. Daily episodes of painless
      pallor of the digit occurred for 1 month upon any exposure to cold, resolving
      with warm water therapy. Symptoms resolved after the initiation of hand therapy,
      splinting, and range-of- motion exercises. 

PMID- 24660213
TI  - Parents' vaccine beliefs: a study of experiences and attitudes among parents of
      children in private pre-schools.
AB  - Even among highly vaccinated populations such as Rhode Island (RI), there exists
      a vulnerability to disease outbreaks. This is the basis for requiring proof of
      immunization for enrollment into school. Although RI grants medical, temporary,
      and religious vaccination exemptions, little is known about the beliefs of RI
      parents who seek exemptions for their children. The purpose of this small-scale,
      cross-sectional, Web-based survey is to describe the vaccine behaviors and
      beliefs of parents of children attending private pre-school in Providence, RI. In
      spite of limitations, the results provided the intended baseline assessment of
      the target population. While such findings should be interpreted with caution,
      they can be used as the foundation for future research and interventions. 

PMID- 24660214
TI  - Quality of internet health information on thumb carpometacarpal joint arthritis.
AB  - INTRODUCTION: The Internet has become a heavily used source of health
      information. No data currently exists on the quality and characteristics of
      Internet information regarding carpometacarpal (CMC) arthritis. METHODS: The
      search terms "cmc arthritis," "basal joint arthritis," and "thumb arthritis" were
      searched using Google and Bing. Search results were evaluated independently by
      four reviewers. Classification and content specific review was performed
      utilizing a weighted 100-point information quality scale. RESULTS: Of the 60
      websites reviewed, 27 were unique pages with 6 categorized as academic and 21 as
      non- academic. Average score on content specific review of academic websites was
      56.8 and for non-academic was 42.7 (p=0.054). Average Flesch-Kincaid Grade Level
      for academic websites was 12.4, and for non-academic was 9.9 (p=0.015).
      CONCLUSION: Internet health information regarding thumb CMC arthritis is
      primarily non-academic in nature, of generally poor quality, and at a reading
      level far above the U.S. average reading level of 6th grade. Higher-quality
      websites with more complete content and appropriate readability are needed.
      CLINICAL RELEVANCE: The quality of Internet health information regarding thumb
      CMC arthritis is suboptimal.

PMID- 24660215
TI  - Health risk profile of Rhode Island's working poor.

PMID- 24660216
TI  - An up-front guide to getting promoted: slow and steady.
AB  - For many years there has been a debate about the explanation for the common
      observation that faculty who sit nearer the front of the conference room at
      departmental grand rounds are more likely to have higher academic rank. There is
      an obvious correlation between rank and age, so that the natural tendency of
      older faculty to be closer to the front in order to hear and see better poses one
      confounding variable. But the underlying questions - whether faculty who sit
      closer to the front get promoted because they sit closer or choose to sit closer
      in order to get promoted or sit closer because they feel more engaged and want to
      participate rather than be more passive, or nap - has never been addressed. It is
      akin to a nature/nurture question, but the truth of the observation has never
      been supported by data. The following study, financed by the Academy, was
      intended to answer this contentious question and provide a path forward. Fifteen
      years ago the Academy funded a large study to investigate this question via a
      long-term, multi-center trial. The following is an analysis of the results.

PMID- 24660217
TI  - Electrochemical sensing of hepatocyte viability.
AB  - We investigated the use of amperometric and chronoamperometric methods with a
      double mediator system and screen-printed electrodes (SPEs) for the
      electrochemical sensing of hepatocyte viability. Cell counts were determined
      based on measuring cellular respiration via interaction of electroactive redox
      mediators. The oxidation currents of chronoamperometric measurement were
      proportional to the concentrations of ferrocyanide which was produced via
      interaction of cellular respiration, succinate and ferricyanide. The integrated
      oxidation charges increased linearly with the density of the cultured primary rat
      hepatocytes over a range of 1 * 10(5) to 5 * 10(5) cells per well (slope = 1.98
      (+/-0.08) MUC per 10(5) cells; R(2) = 0.9969), and the detection limit was 7600
      (+/-300) cells per well based on S/N = 3. Each density of cells was cultured in
      triple replicates and individual cell samples were evaluated. The results of the
      cytotoxic effect of the chronoamperometric method are comparable to those of the
      tetrazolium-based colorimetric assay. The chronoamperometric method with
      ferricyanide and succinate mediators is an efficient, alternative method for
      assessing the viability of primary hepatocytes which can be completed in 20 min.
      Succinate did not provide an efficient electron shuttle between cytosolic
      respiratory redox activity of cancer cells and extracellular ferricyanide, an
      effect that may be useful for distinguishing hepatocarcinoma cells from healthy
      hepatocytes. 

PMID- 24660218
TI  - 3D-printed fluidic devices enable quantitative evaluation of blood components in
      modified storage solutions for use in transfusion medicine.
AB  - A fluidic device constructed with a 3D-printer can be used to investigate stored
      blood components with subsequent high-throughput calibration and readout with a
      standard plate reader. 

PMID- 24660219
TI  - Peptoid helicity modulation: precise control of peptoid secondary structures via
      position-specific placement of chiral monomers.
AB  - The degree of peptoid helicity can be effectively modulated by position-specific
      incorporation of alpha-chiral aromatic monomers. In this study, we report the
      structural role of each monomer position collected from 30 comprehensive model
      peptoid oligomers demonstrating a meticulous manner to fine-tune peptoid
      secondary structures. 

PMID- 24660220
TI  - High-turnover visible-light photoreduction of CO2 by a Re(I) complex stabilized
      on dye-sensitized TiO2.
AB  - Hybrid systems prepared by fixing a Re(i) complex and a dye on three types of
      TiO2 nanoparticles in two different ways commonly revealed persistent
      photocatalysis of the CO2 reduction to CO with no levelling-off tendency under
      visible-light irradiation in DMF, giving a turnover number of >=435. 

PMID- 24660221
TI  - Recent advances in synthesis and applications of clay-based photocatalysts: a
      review.
AB  - Clay materials including clay minerals and layered double hydroxides (LDHs) have
      attracted great attention because of their special layer structures, large
      specific surface areas, and remarkable adsorption capacities. In the past few
      decades, they have been regarded as important components or precursors for making
      various functional materials. This paper aims to review and summarize the recent
      advances in the synthesis and photocatalytic applications of clay-based
      photocatalysts. Moreover, the effects of surface and structural characteristics
      of clay-based photocatalysts on photocatalytic properties are also discussed. The
      clay-based photocatalysts show good application prospects for environmental
      remediation and energy conversion. Especially, H2 generation and reduction of CO2
      into carbon sources can be easily achieved using the LDH-based photocatalysts.
      Meanwhile, the role of clay materials in the photocatalysis is discussed in
      detail. 

PMID- 24660222
TI  - Photoluminescence quenching in compressed MgO nanoparticle systems.
AB  - Efficient use of highly dispersed metal oxides for lighting, energy conversion
      and catalysis requires knowledge about the impact of density and microstructure
      of the powders on the optical nanoparticle properties. For MgO nanocube powders
      we present a combined photoluminescence (PL) and electron paramagnetic resonance
      (EPR) approach which enables for samples of different aggregation states the
      quantification of the fractional powder volume that becomes illuminated with UV
      and visible light during the PL measurements. Using O2 as a PL emission quencher
      and - after light induced exciton separation and oxygen adsorption - as an EPR
      active adsorbate we observed clear aggregation dependent trends in PL emission
      quenching that originate from particle-particle contacts. Upon interaction of low
      coordinated surface elements with the surfaces of adjacent MgO nanocubes, which
      occurs even at powder consolidation levels that escape sorption analysis, the
      radiative decay of excited surface states becomes quenched down to 15% of the
      original intensity. Our results underline the critical role of microstructure and
      the aggregation state of a nanoparticle ensemble with respect to spectroscopic
      properties and related adsorption induced changes. 

PMID- 24660223
TI  - External coronary artery compression due to prosthetic valve bacterial
      endocarditis.
AB  - Acute coronary syndromes in the setting of infective endocarditis may be the
      result of coronary compression secondary to periannular aortic valve
      complications, coronary embolism, obstruction of the coronary ostium due to a
      large vegetation, coronary atherosclerosis, and severe aortic insufficiency.
      External coronary artery compression as a result of infective endocarditis is a
      rare and lethal finding with few reported cases available in the medical
      literature. We present a rare occurrence of an acute coronary syndrome occurring
      in the setting of a bioprosthetic aortic valve abscess in which there was no
      complete coronary occlusion visualized and given the patient's recent
      unremarkable catheterization and findings of diffuse tapering of the proximal
      left coronary system, the most likely etiology was external compression secondary
      to the known aortic root abscess, which caused myocardial ischemia, and was
      confirmed during surgery. Although uncommon, external compression should be
      considered in the differential diagnosis of acute coronary syndrome in this
      setting and coronary angiography can be diagnostic of this entity.

PMID- 24660224
TI  - Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in
      patients with generalized anxiety disorder and a history of inadequate treatment
      response: a randomized, double-blind study.
AB  - BACKGROUND: For many patients with generalized anxiety disorder (GAD), first-line
      treatment does not lead to remission. This study investigated the efficacy and
      tolerability of adjunctive extended-release quetiapine fumarate (quetiapine XR)
      in patients with GAD and an inadequate response to selective serotonin reuptake
      inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
      METHODS: Patients were randomized to quetiapine XR or placebo adjunctive to
      SSRI/SNRIs in an 11-week study. The primary endpoint was change from
      randomization to week 8 in Hamilton Anxiety Rating Scale (HAM-A) total score.
      Secondary variables were HAM-A psychic/somatic clusters, response, and remission,
      and Clinical Global Impression-Severity of Illness (CGI-S) score. RESULTS: A
      total of 409 patients received quetiapine XR (n=209) or placebo (n=200). The week
      8 mean change in HAM-A total score was not statistically significant for
      quetiapine XR (-10.74; P=.079) vs placebo (-9.61). Secondary variables were
      generally consistent with the primary analysis, except for a significant
      reduction in HAM-A total score (week 1) and significant improvements in HAM-A
      psychic cluster and CGI-S total scores (week 8). Adverse events included dry
      mouth, somnolence, sedation, headache, and dizziness. CONCLUSIONS: In patients
      with GAD and an inadequate response to SSRI/SNRIs, adjunctive quetiapine XR did
      not show a statistically significant effect for the primary endpoint at week 8,
      although some secondary endpoints were statistically significant vs placebo.
      Quetiapine XR was generally well tolerated.

PMID- 24660225
TI  - Barriers to utilizing long-acting injectable antipsychotic medications.
AB  - BACKGROUND: Long-acting injectable (LAI) antipsychotic medications are superior
      to their oral equivalents in reducing relapse, yet schizophrenia treatment
      guidelines favor oral formulations. A minority of eligible patients receive LAI
      preparations in the United States. The purpose of the present study is to examine
      barriers faced by psychiatrists in implementing the use of LAI antipsychotics.
      METHODS: An internet survey sent to Michigan State University-affiliated
      psychiatrists examined psychiatrists' practice locations and characteristics,
      access, opinions, and barriers to utilizing LAI antipsychotic medications in
      patients with schizophrenia. Thirty-six psychiatrists completed the survey.
      RESULTS: Thirty-three psychiatrists (83%) acknowledged having patients in their
      practices who would benefit from LAI antipsychotics; however, only 22 (61%) had
      the capacity to utilize these formulations. Barriers to utilizing LAI
      antipsychotic medications included: 1) lack of ancillary support at the practice
      location; 2) personal preference for oral compounds; and 3) limited insurance
      coverage. Psychiatrists who had the capability of administering LAI antipsychotic
      compounds were 10 times more likely to utilize them when compared with others who
      lacked the capacity to do so (9.67% [SD=10] vs 1.43% [SD=3]; df=1; F=8.59;
      P<.005). CONCLUSIONS: Psychiatrists practicing in Michigan face formidable
      barriers to utilizing LAI agents. Strategies to mitigate these barriers are
      reviewed.

PMID- 24660226
TI  - Troubleshooting forum. Molecular biology techniques Q&A.

PMID- 24660227
TI  - Predictors of wait-time for antibiotic initiation and association of wait-time
      with hospital length of stay and ICU admission among children with cancer at the
      Southern Philippines Medical Center.
AB  - BACKGROUND: Expedited antibiotic administration improves the survival of children
      with cancer and infection. A 1-hour antibiotic wait-time (AWT) post-hospital
      arrival is a quality-of-care bench mark in healthcare. However, multiple factors
      preclude achieving this goal in developing countries. Predictors of AWT and its
      association with hospital length of stay (LOS) and intensive care unit (ICU)
      admission at the Southern Philippines Medical Center (SPMC) were identified.
      PROCEDURES: Health and socioeconomic characteristics of 55 children in 92
      admissions who required antibiotics were reviewed;and SPMC care providers about
      institutional capacity and response to suspected infection were surveyed.
      RESULTS: The mean total AWT was 3 days and 15 hours. For admissions of
      established patients, mean total AWT and mean LOS were approximately half that
      for new patients. Admissions from high-income households waited an average 44%
      less for antibiotics and were discharged 43% sooner than those from medium-income
      households. Admissions from residence owner families waited 31% less to receive
      antibiotics, and total AWT for admissions of patients with no insurance was 32%
      less than for those with insurance. The likelihood of ICU admission increased 20%
      with every 1-day increase in total AWT (95% CI: 1.021.42). Only 59% of nurses
      recognized fever as an emergency. CONCLUSIONS: AWT is complex and multifactorial;
      it may be reduced by educating parents and care providers about infection and
      infection control and improving the availability of antibiotics and associated
      supplies. These interventions will most likely reduce ICU admissions and possibly
      LOS and increase the survival of pediatric oncology patients at SPMC.

PMID- 24660228
TI  - The impact of involved node, involved field and mantle field radiotherapy on
      estimated radiation doses and risk of late effects for pediatric patients with
      Hodgkin lymphoma.
AB  - BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with
      Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to
      the thyroid, heart, lungs, and breasts are compared with the extensive mantle
      field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT
      (INRT) and the risk of radiation-induced cardiovascular disease, secondary
      cancers, and the corresponding Life Years Lost (LYL) is estimated with each
      technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were
      simulated for 10 supradiaphragmatic, clinical stage I-II classical HL patients
      <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks
      of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with
      each technique were estimated. The estimated excess risks attributable to RT were
      based on HL series with long-term follow-up, treating death from other causes as
      competing risks. The corresponding LYL were derived from the estimated excess
      risks. Statistical analyses were performed with repeated measures ANOVA. RESULTS:
      Both a reduction in field size and in prescribed radiation dose significantly
      lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to
      past,extended fields, even for patients with mediastinal disease. This translated
      into a significantly reduced estimated risk of cardiovascular disease, secondary
      cancers, and LYL. CONCLUSIONS: Involved Node Radiotherapy should be considered
      for pediatric patients with Hodgkin lymphoma since it is estimated to
      substantially lower the risk of severe long-term complications.

PMID- 24660229
TI  - Erratum to "Toxicity and SOS response to ELF magnetic field and nalidixic acid in
      E. coli cells" [Mutat. Res.: Genet. Toxicol. Environ. Mutagen. 722 (1) (2011) 84
      88].

PMID- 24660231
TI  - Extracellular and intracellular crystal deposition in plasma cell myeloma.

PMID- 24660230
TI  - Fluorinated alternatives to long-chain perfluoroalkyl carboxylic acids (PFCAs),
      perfluoroalkane sulfonic acids (PFSAs) and their potential precursors.
AB  - Since 2000 there has been an on-going industrial transition to replace long-chain
      perfluoroalkyl carboxylic acids(PFCAs), perfluoroalkane sulfonic acids (PFSAs)
      and their precursors. To date, information on these replacements including their
      chemical identities, however, has not been published or made easily accessible to
      the public, hampering risk assessment and management of these chemicals. Here we
      review information on fluorinated alternatives in the public domain. We identify
      over 20 fluorinated substances that are applied in [i] fluoropolymer manufacture,
      [ii] surface treatment of textile, leather and carpets, [iii] surface treatment
      of food contact materials,[iv] metal plating, [v] fire-fighting foams, and [vi]
      other commercial and consumer products.We summarize current knowledge on their
      environmental releases, persistence, and exposure of biota and humans. Based on
      the limited information available, it is unclear whether fluorinated alternatives
      are safe for humans and the environment.We identify three major data gaps that
      must be filled to perform meaningful risk assessments and recommend generation of
      the missing data through cooperation among all stakeholders (industry,
      regulators, academic scientists and the public).

PMID- 24660232
TI  - A double red cells population in a woman with a microcytic anemia.

PMID- 24660234
TI  - AACN data confirm that baccalaureate-prepared nurses are more likely to secure
      jobs soon after graduation.

PMID- 24660233
TI  - Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor
      clinical trial data.
AB  - BACKGROUND: We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a
      CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to
      evaluate standardized approaches to sweat chloride measurement and to explore the
      use of sweat chloride and nasal potential difference (NPD) to estimate CFTR
      activity. METHODS: Sweat chloride and NPD were secondary endpoints in this
      placebo-controlled, multicenter trial. Standardization of sweat collection,
      processing,and analysis was employed for the first time. Sweat chloride and
      chloride ion transport (NPD) were integrated into a model of CFTR activity.
      RESULTS: Within-patient sweat chloride determinations showed sufficient precision
      to detect differences between dose-groups and assess ivacaftor treatment effects.
      Analysis of changes in sweat chloride and NPD demonstrated that patients treated
      with ivacaftor achieved CFTR activity equivalent to approximately 35%-40% of
      normal. CONCLUSIONS: Sweat chloride is useful in multicenter trials as a
      biomarker of CFTR activity and to test the effect of CFTR potentiators.

PMID- 24660235
TI  - ACA will bring more patients to ASCs--but will profits follow?

PMID- 24660236
TI  - [Overall logarithmic index for the characterization of adaptation and regulatory
      systems straining under chronic action of extreme environmental factors].
AB  - The article advertizes some optional capabilities of the overall logarithmic
      index as an integral parameter for quantifying adaptation processes triggered by
      chronic exposure to stress factors of varying intensity. Consideration is given
      to the principles of damage formation in different systems of organism with time
      and subsequent compensatory processes depending on the level of regulation system
      straining, rate of functional potential depletion, probability of remote
      consequences such as early aging, increased risk of lethality and reduction of
      the mean remaining life expectancy. The overall logarithmic index will be used to
      analyze the transition from normal to active insufficient adaptation, and
      possible adaptation failure because of a drastic decline of organism resistance.
      In fact, an attempt was made to use the index to quantify adaptation cost, loss
      of resistance, and possible increase of the risk of remote consequences.

PMID- 24660237
TI  - [Medical monitoring and maintaining safety of cosmonauts on long-duration
      missions].
AB  - The paper considers key methodical, logistics and tactical aspects of enhancing
      cosmonaut's medical monitoring to ensure crew safety in long-duration space
      mission. Activities toward extension of the diagnostic capabilities included
      hardware development, choice of examination procedures and defining the content
      of physiological information that would be necessary and sufficient for
      evaluation, including in real-time, of the cardiovascular system function and
      capacity, planning functional tests procedures as close as possible to the
      generally accepted clinical protocols used in selection of candidates for
      cosmonauts, and pre- and post-flight examination; refining the objective criteria
      of test tolerance and termination, and end-of-mission LBNP training tolerance and
      effectiveness; constructing a fundamentally new structure for medical telemetry
      data acquisition and processing at the Moscow Mission Control Center (MCC-M).

PMID- 24660238
TI  - [Population characteristics of mucous tissue basocytes in the Mongolian gerbil's
      jejunum following the 12-day orbital flight onboard space platform "Foton-M3"].
AB  - Optical (light) microscopy and histochemical techniques were used for the first
      ever studies of the population characteristics of tissue basocytes in the jejunum
      mucous membrane in three groups of gerbils Meriones unguiculatus: flown over 12
      days aboard space platform Foton-M3, subjected to spaceflight factors simulation
      (SFS) in dedicated system Kontur-L (2) and maintained in standard vivarium
      conditions (control). Space flight was shown to induce quantitative and
      qualitative changes in the population of jejunum mucus labrocytes. Reduction of
      the basocytes population, alterations in age composition and ratio of the
      morphofunctional cell types in microgravity were indicative of cytoplasmic
      aggregation intensity, paths of biosynthesis products release into the
      intersticium, and their tinctorial properties. Also, heparin maturation and
      liberalization into the extracellular space in support of the jejunum mucus
      adaptive functions progressed with greater intensity. SFS did not affect size of
      the basocytes population significantly although it did cause qualitative
      rearrangements in the population structure.

PMID- 24660239
TI  - [Histogenesis of Japanese quail bone and cartilage tissues at the final stages of
      embryonic development in microgravity].
AB  - The article reports the results of comparative histological studies of skeleton
      development in 14- and 16-day Japanese quail embryos grown in space flight and in
      the 1-g gravity. The investigation revealed retardation of cartilage replacement
      by bone in the femur and tibia in space embryos as compared with their controls.
      Perichondral ossification metaphysis was reached by day 14 both in the space and
      control embryos. Destruction of cartilaginous diaphysis advanced onto the
      proximal and distal parts including the periphery. Tibia and femur cartilaginous
      cores in space embryos were destructed worse than in the controls in consequence
      of insufficient minerals supply. Perichondral ossification in the 16-day space
      and control embryos was alike close to completion spreading as far as the
      epiphysis. Long bones metaphysis was abundant in monomorphic cells as a growth
      bank existing during and 7 days post hatching. However, absence, in contrast to
      the controls, of osteogensis sites in long bones epiphysis, suggested retardation
      of chondrocytes calcification in these areas, as well as of ossification in space
      embryos.

PMID- 24660240
TI  - [Seasonal dynamics of external respiration and gas exchange in the population of
      northeast Russia].
AB  - In conjunction with the MARS-500, a monthly monitoring of several
      morphofunctional parameters was performed in 19 Caucasoid volunteers born in the
      Magadan region over the period of 18 months. The standard procedures were used
      for somatometric examination and evaluation of the respiratory and cardiovascular
      functions. The greatest straining of these body systems was stated in wintertime.
      However, during summer both systolic and diastolic pressure was also high when
      compared with people living in the center and north of European Russia, which may
      infer a significant effect of seasonal variations in the Magadan environment and
      climate on human organism throughout the year.

PMID- 24660241
TI  - [Cardiovascular function dynamics in healthy Kazakhstan participants of an
      ecomedical investigation working in extreme conditions (emergency management
      personnel)].
AB  - Purpose of the investigation was to study group dynamics of seasonal changes in
      the autonomous nervous and cardiovascular functions in essentially healthy males
      occupationally dealing with stressful situations (field personnel and
      firefighters of the Alma Ata Emergency Management Department (Kazakhstan). The
      investigation was based at the Kazakh National Medical University (Alma Ata) and
      conducted in conjunction and parallel with the MARS-500 project. Methodology
      embodied the pre-nosology approach pointed at identification of states in-between
      the norm and pathology. Results of the year-long investigation demonstrated
      seasonal variations in the functioning of normal organism that could be
      associated with occupational factors and "arduous duty", as it follows from the
      EMD operations summary (autonomous balance shifting toward prevalence of the
      sympathetic control due to the spring and summer "arduous duties" and the
      parasympathetic control in the peaceful situation during wintertime). These
      observations testify to the importance of dynamic health monitoring of normal
      people occupationally exposed to chronic psycho-emotional strain for pre-nosology
      diagnosis and timely preventive intervention.

PMID- 24660242
TI  - [Long-run eco-medical monitoring in North America using the Heart Wizard MARS-500
      system].
AB  - From 2009 through to 2011, a long-run eco-medical monitoring was undertaken as a
      part of satellite project MARS-500. One of the objectives was field testing of
      innovative technologies of human functional state estimation. The monitoring
      protocol was a replica of that in the experiment with 520-day isolation. Heart
      Wizard Mars-500, a telemedical health estimation system based on heart rate
      variability analysis and pre-nosology diagnosis was trialed in the US and Canada.
      First and foremost the pre-nosology monitoring is aimed to estimate potential
      risks of maladaptation. Our results confirm diagnostic comprehensiveness of HRV
      analysis, particularly in long-run systematic health monitoring and when compared
      and contrasted with entries in the health and lifestyle questionnaire and
      functional test data. Heart Wizard Mars-500 is a simple and easy system for home
      use. Individual pre-nosology monitoring, initiation into own functional state and
      potential risk factors may inspire to change way of life and thus to improve
      health and life quality.

PMID- 24660243
TI  - [Effects of small ionizing radiation doses on hemato-encephalic barrier
      permeability].
AB  - Goal and objectives of the study was comparative description and establishment of
      dose-time dependence of changes in permeability of the hemato-encephalic barrier
      (HEB) in phylogenetically different parts of the brain cortex, i.e. new (Fr2 and
      Cg3), old (hippocampal fields CA1-CA4 and dentate fascia) and paleocortex
      (piriform cortex) following exposure to 0.1; 0.2; 0.5 and 1 Gy of ionizing
      radiation (dose rate = 50 cGy). Dependence of microvessels permeability on dose,
      post-exposure time and cortex phylogenetic age was established. Changes in brain
      microvessels, in the phylogenetically young cortex in particular, produced by 0.5
      Gy and 1 Gy remained uncompensated till the end of investigation. Pronounced
      changes persisted over the period of one year after radiation exposure; complete
      recovery was not observed even in the phylogenetically old cortex.

PMID- 24660244
TI  - [Radiobiological effects of total mice irradiation with Bragg's peak protons].
AB  - Outbred CD-1 female mice were irradiated in a proton beam (171 MeV, 5 Gy) on the
      phasotron at the Joint Institute of Nuclear Research (Dubna, Russia). Radiation
      was delivered in two points of the depth dose distribution: at the beam entry and
      on Bragg's peak. Technical requirements for studying the effects of Bragg's peak
      protons on organism of experimental animals were specified. It was recognized
      that protons with high linear energy transfer (mean LET = 1.6 keV/microm) cause a
      more severe damaging effect to the hemopoietic system and cytogenetic apparatus
      in bone marrow cells as compared with entry protons and 60Co gamma-quanta. It was
      shown that recovery of the main hemopoietic organs and immunity as well as
      elimination of chromosomal aberrations take more time following irradiation with
      Bragg's peak protons but not protons with the energy of 171 MeV.

PMID- 24660245
TI  - [Effects of exposure to high-energy protons on rat's behavior and underlying
      neurochemical mechanisms].
AB  - Effects of 1.5 and 3 Gy from high-energy protons (165 MeV) on rat's motor and
      oriented trying activities, rate of the Y-labyrinth learning with electric pain
      stimulation, and levels of monoamines and their metabolites in different brain
      structures were studied. The experimental results showed that irradiation with
      these proton doses caused considerable inhibition of the motor and oriented
      trying activities, and strengthening of passive defense reactions in the open
      field test; however, no significant change was induced in the learning rate or
      monoamines turnover. Apparently, emotional and motivational systems were affected
      to a greater degree than cognitive functions.

PMID- 24660246
TI  - [Calculation of radiation loads in a space station compartment with a secondary
      shielding].
AB  - Doses from space ionizing radiation were estimated using a model of ISS
      cosmonaut's quarters (CQ) outfitted with secondary shielding ("Protective
      shutter" (PS) as part of experiment MATRYOSHKA-R). Protective shutter is a
      "blanket" of water-containing material with mass thickness of - 6 g/cm2 covering
      the CQ exterior wall. Calculation was performed specifically for locations of
      experimental dosimetry assemblies. Agreement of calculations and experimental
      data reaching accuracy - 15% proves model applicability to estimating protective
      effectiveness of secondary shielding in the present-day and future space
      vehicles. This shielding may reduce radiation loading onto crewmembers as an
      equivalent dose by more than 40% within a broad range of orbit altitudes equally
      during the solar minimum and maximum.

PMID- 24660247
TI  - Improving HPV vaccination rates.
AB  - Despite national guidelines and proven health benefits, vaccination rates for the
      human papillomavirus (HPV) remain far below those of other vaccines recommended
      for adolescents. HPV is the most common sexually transmitted infection in the
      U.S; it is responsible for about 25,000 new cancers each year. A series of three
      shots is recommended for all girls and boys at age 11-12, but significant
      barriers exist to starting and finishing this series. This Issue Brief examines
      some of the barriers and summarizes a successful, multipronged clinical
      intervention to improve vaccination rates.

PMID- 24660248
TI  - Brain matters: research into how the brain develops is shaping early childhood
      policies and programs.

PMID- 24660249
TI  - Doctor's orders followed: TMA scores victories despite tough legislative session.

PMID- 24660250
TI  - Saving lives through education.

PMID- 24660251
TI  - Anaesthesia for thoracic surgery 3.

PMID- 24660252
TI  - Extracorporeal respiratory support: breaking conventions?

PMID- 24660254
TI  - [Not Available].

PMID- 24660253
TI  - Continuous transversus abdominis plane catheter technique for postoperative
      analgesia after abdominal surgery.

PMID- 24660255
TI  - [A case of the patient with HBeAg-negative chronic hepatitis B recurrence after
      retreatment with adefovir occurred HBsAg seroconversion].

PMID- 24660256
TI  - [A case report of idiopathic adulthood ductopenia].

PMID- 24660257
TI  - [Role of focal adhesion kinase in alcoholic liver disease].

PMID- 24660258
TI  - Thank you, Dr. Whitaker.

PMID- 24660259
TI  - Workforce. Why it's time to help the helpers.

PMID- 24660260
TI  - Workforce: case studies. Spelling it out loud and clear.

PMID- 24660261
TI  - Safeguarding. Staying safe in an age of austerity.

PMID- 24660262
TI  - Safeguarding: case studies. making it fast and to the point.

PMID- 24660263
TI  - Improving outcomes. Taking the drama out of a crisis.

PMID- 24660264
TI  - Big brother is on your side. CQC TV will help stop care home scandals.

PMID- 24660265
TI  - Get the money for specialised services right.

PMID- 24660266
TI  - Leadership. What the books don't tell you.

PMID- 24660267
TI  - The abortion decline.

PMID- 24660268
TI  - In vitro comparison of stannous fluoride, sodium fluoride, and sodium
      monofluorophosphate dentifrices in the prevention of enamel erosion.
AB  - OBJECTIVE: To compare the relative performance of commercially available
      dentifrices containing different types of fluoride to reduce enamel erosion from
      citric acid. METHODS: Two randomized parallel-group experiments were conducted,
      each with 48 bovine enamel samples randomly divided into six treatment legs. Each
      treatment leg went through 24 toothpaste treatment cycles, acid challenge (0.05M
      citric acid), and remineralization in artificial saliva. Total acid immersion
      after all cycles was 300 minutes for each test product; two test products in
      Experiment 1 were also evaluated for 180 minutes for comparison. Samples were
      analyzed blinded to treatment group for enamel loss by contact profilometry. One
      stabilized stannous fluoride (SnF2) dentifrice was compared to three sodium
      fluoride (NaF) dentifrices, two sodium monofluorophosphate (MFP) dentifrices, and
      one MFP plus calcium sodium phosphosilicate (CSP) dentifrice. All fluoride levels
      were 1450 ppm. A water control was also included. RESULTS: The dentifrice
      containing stabilized SnF2 was significantly (p < 0.0001) better at preventing
      enamel erosion compared to the NaF and MFP dentifrices. The SnF, dentifrice
      provided a 61.7% (p < 0.0001) reduction in enamel loss versus the water control.
      The comparable figures for NaF and MFP dentifrices were 36-39% (p < 0.0001) and
      33% (p < 0.0001) reductions, respectively, compared to the water control. The
      MFP+CSP dentifrice was significantly (p < 0.05) less effective, providing a 23.2%
      (p = 0.0007) reduction versus the water control. CONCLUSION: Of the dentifrices
      included in this research, the stabilized SnF, dentifrice was the most effective
      at reducing enamel erosion from citric acid.

PMID- 24660269
TI  - Fluoride toothpaste containing 1.5% arginine and insoluble calcium as a new
      standard of care in caries prevention.
AB  - In spite of obvious achievements in prevention, caries remains a prevalent
      disease. Fluorides are effective by inhibiting enamel and dentin demineralization
      and enhancing remineralization, but have little or no influence on bacterial
      processes in dental plaque. Dental caries is a continuum of stages from
      reversible, early lesions to irreversible, pre-cavitated lesions and, ultimately,
      to cavities. Prevention should focus on strengthening protective and reducing
      pathological factors, and careful monitoring of the disease state. While fluoride
      and the mineral aspects of caries have been in focus for decades, new insights
      into the etiology of caries have generated novel concepts and approaches to its
      prevention and treatment. The observation that some plaque bacteria can produce
      alkali metabolites and, thus, raise pH or neutralize acid formed in plaque has
      long been known. Such pH rise factors are related to caries susceptibility.
      Nourishing the plaque with substrates that encourage alkali-producing reactions
      is a protective factor in the caries continuum. This article reviews the results
      of clinical studies with a novel toothpaste containing 1.5% arginine, an
      insoluble calcium compound, and fluoride which have demonstrated superior
      remineralization of white spot enamel lesions and rehardening of root surface
      lesions, favorable effects on the de-/remineralization balance, as well as
      superior cavity prevention efficacy compared to toothpaste with fluoride alone.
      Studies have also confirmed formation of ammonia and elevated pH levels in
      subjects using the arginine-containing toothpaste. This novel toothpaste
      effectively combines the established effects of fluoride on de- and
      remineralization with reduction of caries-inducing pathological factors resulting
      from plaque metabolism.

PMID- 24660270
TI  - Cleaning, abrasion, and polishing effect of novel perlite toothpaste abrasive.
AB  - OBJECTIVE: This study was intended to optimize perlite particle size and
      morphology for better tooth cleaning and lower tooth abrasion, and to evaluate
      the performance of a whitening toothpaste containing the optimized perlite
      abrasive for tooth cleaning, abrasion, and polishing. METHODS: Perlite toothpaste
      abrasive samples were prepared by air classifying a commercial expanded perlite
      product. The tooth cleaning and abrasion properties for these classified perlite
      samples were reported via the pellicle cleaning ratio (PCR) and relative dentin
      abrasion (RDA). Performance of the whitening toothpaste containing the optimized
      perlite abrasive in tooth cleaning, polishing, and abrasion was evaluated against
      a widely used synthetic high-cleaning silica. RESULTS: Air classification removes
      large perlite particles and also physically changes perlite particle morphology
      from mostly three dimensional and angular particles to mainly two dimensional and
      platy particles. All the classified samples show good tooth cleaning effect, but
      tooth abrasion decreases significantly with decreasing particle size. Compared to
      high-cleaning silica whitening toothpaste, the whitening toothpaste containing
      the optimized perlite abrasive (PerlClean) is slightly better at tooth cleaning,
      lower in tooth abrasion, and significantly better at tooth polishing.
      CONCLUSIONS: Fine platy perlite particles are effective in tooth cleaning with
      low tooth abrasion. The enhanced performance of optimized perlite toothpaste
      abrasive compared to high-cleaning silica in a whitening toothpaste is attributed
      to the optimized particle size distribution and the unique platy particle
      geometry.

PMID- 24660271
TI  - Superiority of essential oils versus 0.075% CPC-containing mouthrinse: a two-week
      randomized clinical trial.
AB  - OBJECTIVE: The objective of this randomized, examiner-blind, parallel, controlled
      clinical study was to compare the antiplaque/antigingivitis efficacy of an
      essential oil-containing mouthrinse (EO) to a new 0.075% cetylpyridinium chloride
      mouthrinse (CPC) using a two-week experimental gingivitis model with a 5%
      hydroalcohol rinse serving as the negative control. METHODS: After signing
      informed consents and completing baseline examinations, 185 subjects were
      randomized into three groups. Subjects began supervised/recorded rinsing with 20
      ml of their assigned rinse for 30 seconds twice daily for two weeks, with no
      mechanical oral hygiene permitted. Baseline and two-week assessments were
      conducted as follows: Turesky Modification of the Quigley-Hein Plaque Index (PI),
      Modified Gingival Index (MGI), and the Gingival Bleeding Index (BI). Analysis of
      efficacy variables (i.e., mean PI, mean MGI, mean BI, and proportion of bleeding
      sites derived from the BI) was performed using a one-way analysis of covariance
      (ANCOVA). RESULTS: Among the 182 subjects who completed the study, the EO rinse
      showed statistically significant reductions compared to the negative control
      within the range previously reported in this model; PI = 36.5% (p < 0.001) and
      MGI = 17.5% (p < 0.001). A 43.2% reduction in proportion of bleeding sites (p <
      0.001) was demonstrated. Mean PI, MGI, and proportion of bleeding sites at two
      weeks were statistically significantly lower for the EO rinse compared to the CPC
      rinse (p < 0.001), showing 27.7%, 11.9%, and 30.0% reductions, respectively.
      CONCLUSION: An EO rinse provided superior antigingivitis/antiplaque efficacy
      compared to a 0.075% CPC rinse in this short-term clinical trial, and
      demonstrated efficacy within the range shown in previous studies using this
      model.

PMID- 24660273
TI  - Late erosion of an atrial septal occluder device presenting as cardiac tamponade.

PMID- 24660272
TI  - Custom tray application of peroxide gel as an adjunct to scaling and root planing
      in the treatment of periodontitis: results of a randomized controlled trial after
      six months.
AB  - OBJECTIVE: Scaling and root planing (SRP) is the primary non-surgical treatment
      for periodontitis, but its effectiveness is limited. Consequently, various
      adjunctive therapies have been investigated to improve clinical outcome. This
      study evaluated the clinical effects of one SRP procedure alone or combined with
      local administration of hydrogen peroxide gel using customized trays for the
      treatment of subjects with chronic periodontitis over a period of six months.
      METHODS: An examiner-blind clinical trial was conducted among 30 subjects with
      moderate to advanced periodontitis who were randomized to SRP alone or SRP
      combined with prescription custom-tray application (Perio Tray) of 1.7% hydrogen
      peroxide gel (Perio Gel) for a period of three months, then extended to six
      months. Following impressions for the test group, all subjects brushed twice
      daily with a regular dentifrice and toothbrush for a four-week acclimation phase
      to standardize oral conditions (while trays were fabricated) prior to initiating
      the treatment phase. SRP was performed three weeks after baseline, and clinical
      assessments, i.e., pocket probing depth (PPD) and bleeding index (BI), were
      conducted at baseline and after two, five, 13, and 26 weeks of peroxide gel
      applications. Clinical variables were compared by ANCOVA and paired t-tests after
      each treatment interval. RESULTS: A total of 13 test and 15 control subjects
      completed the original three-month trial, of whom 10 test and 13 control subjects
      finished the three-month extension. After two weeks of peroxide gel use prior to
      SRP, mean PPD for the test group significantly decreased from baseline by 0.21 mm
      and mean BI significantly dropped by 0.14; clinical parameters for the control
      group were unchanged. Two weeks following SRP, mean PPD significantly decreased
      from baseline by 0.65 mm for the test group and 0.17 mm for the control; mean BI
      significantly dropped by 0.17 for the test group and 0.05 for the control. Ten
      weeks following SRP, mean PPD decreases were 0.77 mm for the test group and 0.13
      mm for the control, and mean BI reductions were 0.14 for the test group and 0.00
      for the control. For subjects who completed the three-month extension (i.e., 23
      weeks post-SRP), mean PPD decreases were 0.72 mm for the test group and 0.13 mm
      for the control, and mean BI reductions were 0.05 for the test group and 0.01 for
      the control. Analysis of deeper pockets (i.e., > 5 mm at baseline) showed the
      same relationship for PPD, but with larger differences between groups. For
      example, after two weeks of peroxide gel use prior to SRP, mean PPD decreased by
      0.48 mm for the test group compared to 0.04 mm for the control. Two weeks after
      SRP, mean PPD decreased from baseline by 1.40 mm for the test group and 0.60 mm
      for the control, and 10 weeks after SRP by 1.57 mm for the test group and 0.58 mm
      for the control. After the extension (i.e., 23 weeks post-SRP), mean PPD changed
      from baseline by 1.50 mm for the test group and 0.55 mm for the control. With the
      exception of BI at 23 weeks post-SRP, all reductions cited above for the test
      group were statistically significantly different from the control group for both
      PPD and BI for all comparisons. CONCLUSION: When compared with SRP alone,
      clinical improvements in PPD (e.g., -1.0 mm for pockets > 5 mm at baseline) were
      maintained for up to six months after SRP with adjunctive use of 1.7% hydrogen
      peroxide gel, locally administered using prescription customized trays in the
      treatment of subjects with moderate to advanced periodontitis.

PMID- 24660274
TI  - The primary prevention of cardiovascular disease: nurse practitioners using
      behaviour modification strategies.
AB  - Cardiovascular disease (CVD) places great financial strain on the health care
      system and dramatically affects individual quality of life. As primary health
      care providers, nurse practitioners (NPs) are ideally positioned to advise
      clients on risk factor and lifestyle modifications that ameliorate the impact of
      CVD. While the lifestyle targets for CVD prevention are established, the most
      effective means of achieving these goals remain uncertain. Behaviour modification
      strategies, including motivational interviewing (MI) and the transtheoretical
      model (TTM), have been suggested, but neither approach is established as being
      more efficacious than the other. In this paper, evidence on the effectiveness of
      the two approaches for modifying smoking, diet, and exercise behaviour are
      presented, and a recommendation for NP practice is made.

PMID- 24660275
TI  - Focus group research: what is it and how can it be used?
AB  - The focus group research method has been used in a variety of settings over the
      years. The method of using group interviews was described as long ago as 1926.
      Focus groups have been used by large corporations to gather the public's opinions
      regarding their products. In the past 20 years the focus group method has been
      increasingly used in health care research in a variety of settings. Researchers
      use the focus group method in order to obtain in-depth knowledge concerning
      attitudes, perceptions, beliefs and opinions of individuals regarding a specific
      health issue. The purpose of this article is to provide a review of the focus
      group research method. The authors discuss the process, analysis, advantages and
      disadvantages of this qualitative method.

PMID- 24660276
TI  - Continuing to choose a nursing career.

PMID- 24660277
TI  - Staffing shortages compromise care--time for action.

PMID- 24660278
TI  - Who missed the bus?

PMID- 24660280
TI  - Enjoying the differences.

PMID- 24660281
TI  - Apology for text omission.

PMID- 24660282
TI  - Few jobs for graduates.

PMID- 24660283
TI  - The president comments.

PMID- 24660284
TI  - More jobs for new grads.

PMID- 24660286
TI  - Simulation 'very realistic'.

PMID- 24660285
TI  - The role of simulation in nursing education.

PMID- 24660287
TI  - Simulation and 'millenials'--a great fit.

PMID- 24660288
TI  - Caring for a patient with Still's disease.

PMID- 24660289
TI  - Confessions of an (American) hospital administrator.

PMID- 24660290
TI  - Supporting young nurses and students.

PMID- 24660291
TI  - Looking at the culture of nursing through fresh eyes.

PMID- 24660292
TI  - Nursing in a bicultural society.

PMID- 24660293
TI  - Clarifying student delegates' roles.

PMID- 24660294
TI  - Students--a force for change.

PMID- 24660295
TI  - Alternative report presented to MPs.

PMID- 24660296
TI  - NZNO rejects minister's H&S claims.

PMID- 24660297
TI  - Primary health: updating cardiovascular risk assessment tools.

PMID- 24660298
TI  - Nurse gave patient medications not prescribed for him.

PMID- 24660299
TI  - Accessing patient information leads to suspension.

PMID- 24660300
TI  - Nurse censured for misappropriating Tramadol.

PMID- 24660301
TI  - Screening cancer.

PMID- 24660302
TI  - Label lift.

PMID- 24660303
TI  - A troubled Marine's final fight.

PMID- 24660304
TI  - AVDS President's message.

PMID- 24660306
TI  - Crown preparation design: an evidence-based review.
AB  - Evidence-based clinical guidelines for full metal crown preparation design are
      seldom encountered in the veterinary literature. The veterinary literature
      regarding prosthodontic treatment in companion animals is sparse and consists
      primarily of case reports and expert opinion based primarily on clinical
      experience. The goal of this manuscript is to present concepts of evidence-based
      practice, review common recommendations on crown preparation design from the
      veterinary literature, and to provide an assessment of the evidence for or
      against those recommendations.

PMID- 24660305
TI  - Isolation and identification of Porphyromonas spp. and other putative pathogens
      from cats with periodontal disease.
AB  - The purpose of this study was to evaluate the subgingival microbiota and
      determine the most prevalent periodontal pathogens implicated in feline
      periodontal disease and to correlate these findings with the clinical periodontal
      status. Subgingival microbiological samples were taken under sedation from 50
      cats with clinical signs of periodontal disease. Pooled paper point samples from
      4 selected subgingival sites were cultured on blood agar and on Dentaid-1 medium.
      Suspected pathogens were identified, subcultured, and preserved. The association
      between the microbiological findings and the clinical status was studied using
      correlation coefficients (CC). In addition, cats were stratified in subgroups
      according to presence of putative pathogens, and comparisons were carried out
      using unpaired t-test. Three bacterial species were frequently detected including
      Porphyromonas gulae (86%), Porphyromonas circumdentaria (70%) and Fusobacterium
      nucleatum (90%). The mean proportion of total flora was high for P. gulae
      (32.54%), moderate for P. circundentaria (8.82%), and low for F. nucleatum
      (3.96%). Among the clinical variables, tooth mobility was correlated (CC > 0.50,
      p < 0.001) with recession, pocket depth, attachment level, gingival index, and
      calculus index (CC = 0.29, p = 0.04) as well as with total bacterial counts (CC =
      0.38, p = 0.006). Cats with more than 10% of P. gulae showed significantly more
      mobility (p = 0.014) and recession (p = 0.038), and a tendency for deeper probing
      pocket depths (p = 0.084) and attachment loss (p = 0.087). The results from this
      cross-sectional study confirmed that P. gulae is the most relevant pathogen in
      periodontal disease in cats.

PMID- 24660307
TI  - Complications associated with cheek tooth extraction in the horse.
AB  - Common indications for cheek tooth extraction in the horse include dental
      fracture, periodontal disease, severe decay/ caries, mandibular fracture with
      alveolar/tooth involvement, and periapical abscess. Complications secondary to
      extraction of cheek teeth are prevalent. Typical complications may include
      retained root tip(s), collateral damage of neighboring teeth and alveolar bone,
      mandibular fracture non-union or delayed union, cemental ankylosis, dilacerated
      root(s), oroantral/oronasal fistula, palatal deviation of cheek teeth, bone
      sequestration, sinus involvement, alveolar plug failure, and palatine artery
      laceration. This paper presents a series of cases that had complications
      following cheek tooth extraction. Anticipation of problematic extractions,
      recognition of complications, and appropriate treatment will aid the clinician in
      managing the inevitable cheek tooth extraction complication.

PMID- 24660308
TI  - Thermoplastic inclined plane aligner for correction of bilateral mandibular
      canine tooth distoclusion in a cat.
AB  - Mandibular brachygnathia was the etiology for moderate mandibular distoclusion
      and bilateral palatal canine cusp penetrations in a kitten. The course of
      treatment included deciduous canine tooth exodontia, tooth extensions, and
      ultimately, aligners that incorporated inclined planes fabricated from a
      thermoplastic sheet that was "indirectly" vacuum thermoformed over a dental
      model. The thin, flexible aligners fit over the rostral maxillary teeth and
      palate, and were retained by a snug fit on the slightly divergent maxillary
      canine teeth. Advantages over "directly" applied composite inclined planes
      include: serial gradations of angulations for more gradual tooth movement,
      elimination of dental trauma from composite adhesions and removals, owner
      removable and cleanable appliances, and a single anesthetic event required for
      dental impressions. Five progressively angled aligners were used sequentially
      over a 3-month period to achieve atraumatic "clinical" neutroclusion of the
      rostral dentition.

PMID- 24660309
TI  - Odontoameloblastoma in a calf.

PMID- 24660310
TI  - Consequences of untreated periodontal disease in dogs and cats.

PMID- 24660311
TI  - Biopsy of the temporal and masseter muscles in the dog.

PMID- 24660312
TI  - Academic scholarship redefined.

PMID- 24660313
TI  - What is personal health responsibility?
AB  - PURPOSE: This case study examined the meaning of personal health responsibility
      from the perspective of the individual. METHOD: A single Black female, 20 years
      of age, was interviewed for the study. Content analysis was used for data
      evaluation. FINDINGS: The meaning of personal health responsibility grouped into
      four categories: listing of tasks, obligating to tasks, following through with
      tasks, and maintaining resources. Tasks are behaviors performed to care for
      oneself. Obligating to tasks is the attitude towards carrying out behaviors.
      Following through is the actual completion of a task. Maintaining resources is
      the support needed to care for oneself. IMPLICATIONS: The individual's definition
      of personal health responsibility should be considered when making healthcare
      decisions and designing treatment plans. Future research should examine the
      meaning of personal health responsibility among diverse populations and explore
      factors that serve as facilitators and barriers to personal health
      responsibility.

PMID- 24660314
TI  - Weight changes in African American college students: a review of literature.
AB  - Over one-third of all adults in the United States are obese and African Americans
      represent over 49.5% of these cases. Young adults with some college education
      show the most rapid increase in the prevalence of overweight and obesity, with
      African Americans leading among all groups. The purpose of this paper is to
      consider why students gain weight in college and if racial and ethnic differences
      exist in the context of weight gain. Both physical environment and psychological
      factors affect the college students' weight-related behaviors. College students
      experience significant increases in their weight and African Americans are
      disproportionately affected. However, the role of race and ethnicity is under
      examined. Future research should explore racial and ethnic differences in weight
      gain in college students.

PMID- 24660315
TI  - Effects of patients and hospital characteristics on myocardial infarction
      mortality: health disparity outcomes.
AB  - OBJECTIVE: To evaluate if patient characteristics would have significant effects
      on outcomes for inpatients' Myocardial Infarction (MI) with Type 2 diabetes (T2D)
      admitted to Non-Federal Hospitals. METHODS: We used data from the Healthcare Cost
      and Utilization Project under the Agency for Healthcare Research and Quality
      (HCUP_AHRQ, 2006) and data were retrospectively analyzed. This database was the
      latest HCUP data available in 2008, when the study was initiated. RESULTS: There
      were significant results noted in healthcare outcomes between age, gender,
      insurance and patient mortality with gender and patient insurance (p < .001).
      Male inpatients had more major procedures than their female counterparts (p <
      .001). Treatment procedure effect on patient mortality was highly significant for
      age (p < .001) and gender (p < .0001), and more females died than expected (p <
      .001). CONCLUSIONS: The implication of this study to practice is that healthcare
      could be more cost effective if healthcare providers are to screen and treat all
      patients that present with diabetic mellitus for heart and other related
      diseases. This venture would help detect and prevent myocardial infarction before
      it occurs. Discharged patients need to be followed as well to prevent frequent
      admissions. Prevention is better than cure.

PMID- 24660316
TI  - An examination of postpartum African American adolescents' sociocultural beliefs,
      perceptions of body weight, and weight control behaviors.
AB  - Obesity presents a public health challenge and is a serious chronic medical
      condition that is associated with multiple co-morbidities and reduced
      survivability/longevity. African American adolescents who retain weight after
      pregnancy are at the highest risk of becoming obese adults. Obesity is associated
      with 300,000 deaths per year and expected to cost the US. health care system over
      237 million dollars within the next decade. The prevalence of obesity is cause
      for concern because of its economic costs and its toll in human suffering due to
      related morbidity and mortality. This study seeks to understand the meaning or
      essence of the lived experience of obesity among postpartum African American
      adolescents based on a literature review indicating the need for such a
      qualitative research. Understanding the influence of their developmental stage,
      sociocultural perceptions, and perceptions of postpartum weight retention could
      help develop population-specific interventions that could reduce the health risk
      of obesity.

PMID- 24660317
TI  - A personal experience in the presence of a man who transformed a nation and
      changed the world: Nelson Mandela.
AB  - At this time in history, I consider myself very privileged to have spent some
      three hours in the presence of President Nelson Mandela as a Howard University
      faculty member in the late 1990s. Then, President of Howard University, H.
      Patrick Swygert bestowed upon President Nelson Mandela, Esquire an Honorary
      Doctorate of Human Letters. I can only equate this experience to my four mile
      walk up the Bedaling Wall (Great Wall) in China (a magnificent ancient wonder of
      the world), and trying to relate this event to something only fortunate souls
      have had the chance to enjoy. I also treasure the once in a lifetime visit to the
      Republic of South Africa in 1998 when the Association of Black Nursing Faculty,
      Inc., Chi Eta Phi Nursing Sorority, Inc., and the Department of Nursing
      (University of Botswana) sponsored the trip as an attempt to establish
      partnerships, share common interests and discussion in how to meet health needs
      of emerging majority and disadvantaged populations in the world, including
      mainly, the continent of Africa, in the 21st century. This short memoir can only
      piggy-back the massive coverage in the media that began almost instantly as a
      long anticipated event (death of Nelson Mandela), but startled upon its
      occurrence.

PMID- 24660318
TI  - Free Willy--and all his pals. Orcas and elephants are smart, social and way too
      large for captivity.

PMID- 24660319
TI  - The case for banning trans fats. The FDA's new policy on these deadly artificial
      fatty acids is long overdue.

PMID- 24660320
TI  - The brain's fix-it brigade. Naturally occurring "exosomes" show promise for
      repairing nerve damage.

PMID- 24660321
TI  - Sun chaser. A hybrid concept car would use solar power for short trips.

PMID- 24660323
TI  - The storm next time. The energy secretary talks about buffering infrastructure
      against the next Hurricane Sandy.

PMID- 24660322
TI  - Thought control. Imagination triggers some of the same physical mechanisms
      involved in actual sight.

PMID- 24660324
TI  - Space: the final medical frontier. Are overeager space tourists endangering their
      health?

PMID- 24660325
TI  - Future imperfect. Asimov's forecast from 1964 shows how far we still have to go.

PMID- 24660327
TI  - Dwarf galaxies and the dark web.

PMID- 24660326
TI  - The new century of the brain.

PMID- 24660328
TI  - Gene therapy's second act.

PMID- 24660329
TI  - The oldest rocks on earth.

PMID- 24660330
TI  - The case of the stolen words.

PMID- 24660331
TI  - The American chestnut's genetic rebirth.

PMID- 24660332
TI  - Why good thoughts block better ones.

PMID- 24660333
TI  - The awe delusion. What does the magnificence of the universe have to do with God?

PMID- 24660334
TI  - Filth in the spice rack. Imported seasonings are rife with all sorts of extras.

PMID- 24660335
TI  - Ego state therapy and hypnosis.

PMID- 24660336
TI  - Healing the wounded self: combining hypnotherapy with ego state therapy.
AB  - The purpose of this article is to formulate a theoretical conceptualization for
      utilizing ego state therapy (EST) as an adjunct with cognitive hypnotherapy (CH)
      for depression. As the relationship between life events and onset of depression
      is very complex, it is not clear from current literature how stressors cause
      depressive symptoms. The notion of "wounded self," derived from the work of Wolfe
      (2005, 2006), is examined as a potential unifying concept for binding the role of
      risk factors in the precipitation of depression. By incorporating wounded self,
      the circular feedback model of depression, on which CH for depression is based,
      is expanded. This revised version provides conceptual and empirical underpinnings
      for integrating EST with CH in the management of depression.

PMID- 24660337
TI  - Mending fences: repairing boundaries through ego state therapy.
AB  - Ego state therapy has often been cited as an effective treatment to help repair
      fragmentation related to posttraumatic stress and dissociative disorders. This
      article explores how specialized work with ego states can help to clarify and
      strengthen internal and external boundaries, create greater boundary flexibility,
      and contribute to containment and self-regulation. Applications of direct and
      indirect hypnosis to repair boundary issues through ego state therapy are
      emphasized, and clinical case examples are used to illustrate results.

PMID- 24660338
TI  - The center core in ego state therapy and other hypnotically facilitated
      psychotherapies.
AB  - Center core phenomena have been utilized in the practice of ego state therapy and
      other forms of hypnotically facilitated psychotherapy for nearly 40 years.
      Despite the frequency with which they are employed, many confusions,
      contradictions, and questions remain concerning them. In this article relevant
      center core phenomena literature is reviewed and an essential differentiation
      between two different kinds of center core phenomena is clarified. Psychodynamic
      explanations are offered for the therapeutic benefits of archetypal center core
      experiences such as inner strength and inner wisdom. The information provided
      offers clinicians a sturdier platform from which to decide whether to incorporate
      center core experiences into clinical practice. The persistent question of
      whether center core phenomena are ego states is revisited and addressed.

PMID- 24660339
TI  - Evidence based abreactive ego state therapy for PTSD.
AB  - A single 5-6 hours manualized abreactive ego state therapy session has recently
      been subjected to two placebo-controlled investigations meeting evidence-based
      criteria. Ego state therapy was found to be a highly effective and durable
      treatment for posttraumatic stress disorder. Apparently, ego state therapy works
      because it is emotion focused, activates sub-cortical structures, and because the
      supportive, interpretive therapist reconstructs the patient's personality to be
      resilient and adaptive. In this article the author reviews the treatment
      procedures and presents the findings of both studies.

PMID- 24660340
TI  - Phenomenological and evidence based research in ego state therapy: recognized and
      unrecognized successes and future directions.
AB  - The status of research in ego state therapy is examined against the backdrop of
      20th and 21st century developments in the philosophy of science and the emerging
      recognition of the subjective as a vital element in all science. Attention is
      paid to the phenomenological method because until recently phenomenological
      studies have been the basis for the standards of care and training in ego state
      therapy as well as in many aspects of hypnotically facilitated psychotherapy. The
      importance of bringing an end to the "science wars" through the integration of
      the subjective and the objective, of phenomenological studies and evidence-based
      studies in ego state therapy and hypnosis research, is proposed.

PMID- 24660341
TI  - Ignore the myths about NHS competition. The debate about the OFT's role is a
      sideshow.

PMID- 24660342
TI  - How we bridged the gap between community and acute care.

PMID- 24660343
TI  - The problem with accountability.

PMID- 24660344
TI  - The case for equipment investment.

PMID- 24660345
TI  - Testing times for pathology.

PMID- 24660346
TI  - 'End of life care is a litmus test for the whole of the NHS'.

PMID- 24660347
TI  - Innovation. Franchising is a recipe for success.

PMID- 24660348
TI  - Patient safety. Weekend surgery just got safer.

PMID- 24660350
TI  - The right tools.

PMID- 24660349
TI  - Workforce. Improve on equality in the NHS.

PMID- 24660351
TI  - New spinal immobilization techniques.

PMID- 24660352
TI  - Author reply: To PMID 24475615.

PMID- 24660353
TI  - A fine line.

PMID- 24660354
TI  - Twist & shout.

PMID- 24660355
TI  - Precious minutes.

PMID- 24660356
TI  - A commonsense review.

PMID- 24660357
TI  - Care without boundaries.

PMID- 24660358
TI  - Saving more lives?

PMID- 24660359
TI  - The 'Patient experience' revolution.
AB  - We're arguably at the most pivotal time in our young profession. The ACA has
      provided EMS an unprecedented opportunity to become a part of the healthcare
      system, a move that many of us have dreamed about for decades. We need to pay
      attention to the changing dynamics of the environment in which we operate. The
      factors that currently impact hospitals, doctors and other healthcare providers
      will also impact us sooner than we think. Take the time to help shape our future
      and how we participate in this new healthcare system. It's time to focus on the
      patient and the patient's experience with our service. Wayne Gretzky said two
      important things during an interview when he was asked what makes him such a
      great hockey player. One was, "You miss 100% of the shots you don't take." The
      other was, "A good hockey player plays where the puck is. A great hockey player
      plays where the puck is going to be. I skate to where the puck is going to be,
      not where it has been." Our advice to you is to go ahead, take the shot, get
      ahead of the other team and focus on improved customer satisfaction sooner rather
      than later.

PMID- 24660360
TI  - Rightsizing.

PMID- 24660361
TI  - Genetic disorders.

PMID- 24660362
TI  - Old friends.

PMID- 24660363
TI  - Learned helplessness.

PMID- 24660364
TI  - Sleepwalking the walk.

PMID- 24660365
TI  - Taking an active role.

PMID- 24660366
TI  - Time for concierge medicine?

PMID- 24660367
TI  - Never relax--and always do what's best.

PMID- 24660368
TI  - Concierge medicine: on the verge of something big?

PMID- 24660369
TI  - Where we practice: Savannah.

PMID- 24660370
TI  - A review of value-based purchasing.

PMID- 24660371
TI  - A year of evolution at the American Medical Association.

PMID- 24660372
TI  - Do you want to be my friend?

PMID- 24660373
TI  - All in the family? A case of heart failure after pregnancy.

PMID- 24660374
TI  - Don't let your practice's Medicare enrollment "perish".

PMID- 24660375
TI  - Prescription drug monitoring in Georgia.

PMID- 24660376
TI  - Critically important proposed Stark changes to physicians.

PMID- 24660377
TI  - HIPAA update: changes to notice of privacy practices and new requirements for
      analyzing breaches.
AB  - Timely compliance with the 2013 Omnibus Rule requires health care providers to
      review their NPPs and use the new breach risk assessment standard beginning on or
      after September 23, 2013.

PMID- 24660378
TI  - Failure to follow office policy results in problems for defense.

PMID- 24660379
TI  - On being a Coca-Cola baby, ODD, and having CRH.

PMID- 24660380
TI  - [IgG4-related disease--a common denominator of many conditions previously
      regarded as being confined to a single organ].
AB  - IgG4-related disease is a newly recognized systemic condition characterized by
      high serum IgG4 levels and an inflammatory reaction rich in IgG4-positive plasma
      cells associated with fibrosis and obliterative phlebitis. It predominantly
      affects middle-aged or elderly males and was first described as autoimmune
      pancreatitis. The disease may also involve the hepatobiliary tract, salivary
      glands, orbit, lymph nodes, and the lungs, aorta, retroperitoneum, skin, nervous
      system, kidneys and thyroid gland. It may mimic infections, malignancies, and
      other immune-mediated conditions. Histopathology and immunohistochemistry form
      the basis of the diagnosis. Glucocorticoids are usually effective but relapses
      occur commonly.

PMID- 24660381
TI  - [Current treatment of acute leukemias in adults].
AB  - In addition to conventional microscopic morphology, immunophenotyping by flow
      cytometry as well as chromosome and molecular genetic studies are important
      methods in the diagnosis of acute leukemias. They are utilized for reaching a
      specific diagnosis, estimating the prognosis and looking for markers applicable
      to the examination of minimal residual disease. By means of combination
      chemotherapy and allogeneic stem cell transplantation more than 50% of patients
      under the age of 66 survive five years or more. The picture of the pathogenesis
      and behavior of leukemias is becoming clearer and new targets for drug therapy
      are being revealed.

PMID- 24660382
TI  - [Cognitive functions in severe psychotic disorders].
AB  - Cognitive functions in schizophrenia exhibit a widely mixed nature. A specific
      neuropsychological core disturbance typical of schizophrenia still remains to be
      defined. Disturbances of cognitive function that do not qualitatively differ from
      those associated with schizophrenia are observed also in other severe psychotic
      disorders. Cognitive disturbances may even be more significant than other
      symptoms of disease for the patient's overall condition and coping with daily
      life. Neuropsychological examination is an essential part of assessment of the
      total care and rehabilitation of a patient with psychosis.

PMID- 24660383
TI  - [Acetylsalicylic acid and prevention of preeclampsia].
AB  - Two to six percent of all pregnant women develop preeclampsia. In the worst case
      its complications threaten the life of both the fetus and the mother. It seems
      that especially an early and severe preeclampsia diagnosed before 34 weeks of
      pregnancy can be prevented by using low-dose acetylsalicylic acid medication,
      which shall be started sufficiently early, not later than pregnancy week 16.
      Acetylsalicylic acid is safe during pregnancy at a daily dose of 100 mg. For the
      prevention of preeclampsia, it is worth considering for women who are at high
      risk of developing the disease.

PMID- 24660384
TI  - [Acute mastoiditis in children].
AB  - Acute mastoiditis in children develops when acute otitis media (AOM) spreads into
      the mastoid air cells inside the temporal bone. The diagnosis is based on
      clinical findings of AOM with simultaneous signs of infection in the mastoid
      area. The most common pathogen causing acute mastoiditis in children is
      Streptococcus pneumoniae. Intravenous antimicrobial medication, tympanostomy and
      microbial sample are the cornerstones of the treatment. If a complication of
      mastoiditis is suspected, imaging studies are needed, preferably with magnetic
      resonance imaging. The most common complication of acute mastoiditis is a
      subperiosteal abscess.

PMID- 24660385
TI  - [Rehabilitation outcomes and return to work after psychiatric examination of work
      ability].
AB  - The aim of the study was to find out the rehabilitation outcomes and predictors
      of return to work after psychiatric examination of work ability. Methods. The
      examination and one-year follow-up were performed at Helsinki University Central
      Hospital Psychiatric outpatient unit for the assessment of function and capacity.
      Results. The occupational activity, self-reported functional capacity and quality
      of life were enhanced. Half of the vocational rehabilitation plans were
      successful. Conclusions. An absence of less than 6 months and active return to
      work strategies at occupational health care in co-operation with psychiatrists
      lead to better outcomes.

PMID- 24660386
TI  - [An urinary catheter slipped into the renal pelvis].
AB  - An elderly woman was referred to hospital because of fever and deterioration of
      her general condition. Due to urinary retention, the woman had undergone long
      term catheterization and had a urinary infection for years. In addition, the
      partial right hip prosthesis was found to be dislocated. While changing the
      catheter it slipped into the renal pelvis, and the balloon of the catheter was
      filled at the level of the ureteropelvic junction. The condition, observed in
      computed tomography scanning, was quickly restored, and the patient managed to
      avoid complications. Drifting of an urethral catheter into the upper urinary
      tract is a rare condition, but may lead to significant complications.

PMID- 24660387
TI  - [Febrile episodes of unknown origin, elevated level of plasma ferritin and
      rapidly developed multiorgan dysfunction].
AB  - A previously healthy 40-year-old man developed febrile episodes of unknown
      origin, articular symptoms, venous occlusion of the lower limb and transient
      elevation of hepatic enzymes, and cutaneous symptoms. Computed tomography
      scanning revealed enlarged lymph nodes, but no sample was collected. In addition
      to microcytic anemia, a high serum ferritin level and an increased IL-2 receptor
      value in serum were found. Drug therapy against tuberculosis and borreliosis was
      started, but febrile episodes continued and in a few days the patient developed
      multiorgan dysfunction. Hemophagocytic lymphohistiocytosis associated with T-cell
      lymphoma was revealed as the underlying condition.

PMID- 24660388
TI  - Signup surge raises hopes, questions.

PMID- 24660389
TI  - AMAs ICD-10 report finds higher costs for implementation; software upgrade cited.

PMID- 24660390
TI  - Fragmented care.

PMID- 24660391
TI  - Honoring trustees who made a difference. Helping Dallas' public hospital survive
      a near-death experience.

PMID- 24660392
TI  - Honoring trustees who made a difference. Connecting with the community.

PMID- 24660394
TI  - When an ounce of prevention is worth an ounce of cure.

PMID- 24660393
TI  - Honoring trustees who made a difference. Rebuilding a hospital's reputation.

PMID- 24660395
TI  - Protect the 340B drug program.

PMID- 24660396
TI  - Making virtual care a widespread reality.

PMID- 24660397
TI  - UPMC uses patient 'flight plans' to streamline operating room flow.

PMID- 24660398
TI  - CEO brings luxury hotel lessons to cancer care.

PMID- 24660399
TI  - Largest behavioral health providers.

PMID- 24660400
TI  - Could I choose ... and yet do otherwise?

PMID- 24660401
TI  - SADA communique.

PMID- 24660402
TI  - Evaluation of surface characteristics of titanium and cobalt chromium implant
      abutment materials.
AB  - INTRODUCTION: Micro-organism adhesion and plaque formation is affected by surface
      free energy (SFE), surface roughness, hydrophilicity, surface chemistry, surface
      charge and the presence of proteins. AIMS: The aim of this study was to assess
      and compare surface characteristics of surgical grade cobalt chromium alloy (CCM)
      and of commercially pure titanium (cpTi). METHOD: Nine metallic cylinders were
      machined to precise standards from each material. Surface roughness was measured
      at four different points on each sample and the average Ra value was calculated
      for each material. Contact angles were obtained using the sessile-drop method and
      applied in calculating the SFE. Surface hardness was evaluated by means of a
      Vickers hardness micro-indentation. RESULTS: Surface roughness was similar for
      both metals, but total SFE values and Vickers surface hardness scores showed
      significant differences (p < 0.0001). CONCLUSION: SFE analysis showed CCM to be
      more hydrophobic and that oral bacteria might therefore be less adherent than to
      cpTi. The mean Vickers Hardness scores of the cpTi were significantly lower (p <
      0.0001), suggesting that CCM may be more resistant to surface modifications and
      surface roughening, thus remaining smoother with less plaque accumulation than
      cpTi. This study demonstrated that CCM might be a suitable alternative implant
      abutment material.

PMID- 24660403
TI  - Practice-based, clinical trial of a silorane-based composite resin system in
      posterior teeth.
AB  - INTRODUCTION: Newer monomer systems have been introduced in an attempt to improve
      the success rate of direct composite restorations by minimising shrinkage. AIMS
      AND OBJECTIVES: To evaluate the in vivo performance of a silorane-based resin
      composite system (Filtek Silorane, also known as P90), used together with a two
      step self-etch bonding system (P90 System Adhesive, Self-Etch Primer and Bond),
      for the restoration of Class I and Class II cavities in human permanent posterior
      teeth. MATERIALS AND METHODS: A total of 53 restorations were completed and
      patients were recalled one year later. The restorations were assessed by two
      ndependent clinicians, using the Modified U.S. Public Health Service evaluation
      criteria for the following parameters: retention, colour match, marginal
      discolouration, secondary caries, anatomic form, marginal adaptation, surface
      texture, occlusal and interproximal contacts. RESULTS: Of the 41 restorations
      assessed at the one year follow-up, 92.7% showed clinically acceptable scores for
      all the parameters evaluated. Cronbach's alpha values ranged from 0.72-1.00
      showing a good inter-examiner agreement and reliability. CONCLUSION: Silorane
      based composite, Filtek Silorane, when used in conjunction with the recommended
      adhesive system showed a clinically acceptable performance in posterior teeth
      restorations over a one year clinical service.

PMID- 24660404
TI  - The prevalence of HIV associated oral lesions among adults in the era of HAART.
AB  - INTRODUCTION: The overall prevalence of HIV associated oral lesions among adults
      has decreased since the advent of highly active anti-retroviral therapy (HAART).
      AIMS AND OBJECTIVES: This study describes the prevalence and types of oral
      mucosal lesions in adults, who accepted a dedicated oral and dental programme for
      HIV-infected patients. The incidence of oral lesions and the CD4 cell counts on
      those patients, were related to cases receiving HAART and to those who were not.
      DESIGN: This was a retrospective, descriptive cross-sectional study. METHODS:
      Patients were interviewed, using a structured questionnaire to obtain information
      regarding medical history, current medications and demographic details. Data
      relating to CD4 cell counts were extracted from clinical medical records of the
      patent. In each case, the oral cavity of the sitting patient was examined under
      artificial light, by a clinician using a mouth mirror. Oral lesions were
      categorised in accordance with EC-Clearinghouse diagnostic criteria. RESULTS: The
      prevalence of HIV-associated oral lesions was significantly reduced (p < 0.001)
      in patients receiving HAART. There was, however, no significant difference (p =
      0.29) in mean CD4 counts between patients receiving HAART and those not receiving
      HAART. The presence of oral lesions was statistically significantly, associated
      with both CD4 counts of < 200 cells/mm3 (p < 0.001) and the absence of HAART (p =
      0.033). CONCLUSIONS: The study confirmed that the incidence of oral lesions and
      of pseudo-membranous candidiasis in particular, were statistically significantly
      reduced in patients receiving HAART.

PMID- 24660405
TI  - Maxillo-facial radiology case 114. Idiopathic hypoparathyroidism.

PMID- 24660407
TI  - Dental radiography--importance of selection criteria.

PMID- 24660406
TI  - Oral medicine case book 53: radiation-induced xerostomia.

PMID- 24660408
TI  - Reclaiming, restoring and celebrating our living heritage.

PMID- 24660409
TI  - It is all about communication!!

PMID- 24660410
TI  - A 'clinical' comparison: dental care in the maintenance of potholes Tooth decay
      vs road decay!: at a 'wits end'.

PMID- 24660411
TI  - Amelogenesis imperfecta: a diagnostic and pathological review with case
      illustration.
AB  - Amelogenesis mperfecta is an inherited disorder of enamel development, which
      results n morphological defects of both the primary and secondary dentition,
      usually in the absence of systemic involvement. Mutational defects involving the
      genes that encode for enamel matrix proteins and proteinases are mplicated in
      this disorder. The phenotypic expression is variable, spanning a spectrum from
      barely discernible changes to severe aesthetic and functional enamel defects. The
      specific type and location of the genetic mutation, as well as the mode of
      inheritance, determine the clinical presentation Clinical recognition and early
      therapeutic intervention are required for the most successful outcome. An
      essentia component of the treatment process includes patient counselling and
      education. Patient management requires a dedicated multi-disciplinary approach.
      The disorder is reviewed here with emphasis on the clinical significance for the
      oral healthcare worker. In addition, a case is presented in order to provide an
      example of treatment panning and dental management.

PMID- 24660412
TI  - Alveolar ridge preservation immediately after tooth extraction.
AB  - Ridge preservation procedures immediately after tooth extraction, are commonly
      used with a view to minimising remodelling and shrinkage of the alveolar ridge,
      associated with socket healing. These procedures may sometimes be effective, but
      they cannot completely prevent reduction in dimension of the ridge. Certain
      biomater als used may actually hamper normal deposition of bone within the
      healing socket, reducing bone trabeculae that can integrate with the implant
      surface. However, in extraction sockets in alveolar ridges of low bone density,
      particles of implanted bone substitute incorporated in the healing bone, may
      enhance the mechanical support for the implant, provided by normal healed bone of
      low trabecular density alone. This paper reviews biological rationales and
      procedures for ridge preservation immediately after extraction and comments on
      their clinical use.

PMID- 24660413
TI  - Visual and digital comparative tooth colour assessment methods and atomic force
      microscopy surface roughness.
AB  - This study compared digital and visual colour tooth colour assessment methods in
      a sample of 99 teeth consisting of incisors, canines and pre-molars. The teeth
      were equally divided between Control, Ozicure Oxygen Activator bleach and
      Opalescence Quick bleach and subjected to three treatments. Colour readings were
      recorded at nine intervals by two assessment methods, VITA Easyshade and VITAPAN
      3D MASTER TOOTH GUIDE, giving a total of 1782 colour readings. Descriptive and
      statistical analysis was undertaken using a GLM test for Analysis of Variance for
      a Fractional Design set at a significance of P < 0.05. Atomic force micros copy
      was used to examine treated ename surfaces and establish surface roughness.
      Visual tooth colour assessment showed significance for the independent variables
      of treatment, number of treatments, tooth type and the combination tooth type and
      treatment. Digital colour assessment indicated treatment and tooth type to be of
      significance in tooth colour change. Poor agreement was found between visual and
      digital colour assessment methods for Control and Ozicure Oxygen Activator
      treatments. Surface roughness values increased two-fold for Opalescence Quick
      specimens over the two other treatments, implying that increased light scattering
      improved digital colour reading. Both digital and visual colour matching methods
      should be used in tooth bleaching studies to complement each other and to
      compensate for deficiencies.

PMID- 24660414
TI  - Maxillo-facial radiology case 115. Hyperparathyroidism.

PMID- 24660415
TI  - Oral medicine case book 54: bisphosphonate-related osteonecrosis of the jaw.

PMID- 24660416
TI  - Endodontic treatment--reamers do break.

PMID- 24660417
TI  - Periondontitis and systemic health.

PMID- 24660418
TI  - It is all about communication!

PMID- 24660419
TI  - Endodontic and restorative management of a lower molar with a calcified pulp
      chamber.

PMID- 24660420
TI  - Dental caries among disabled individuals attending special schools in Vhembe
      district, South Africa.
AB  - OBJECTIVES: To determine the prevalence of dental caries among disabled
      individuals attending special schools in Vhembe districts. MATERIAL AND METHODS:
      A cross-sectional descriptive study was conducted from January to June 2012 among
      disabled individuals receiving special care in four specialised schools of Vhembe
      District. The research protocol had been approved by the Ethics Committee of the
      University of Limpopo, Polokwane Campus. Informed consent was obtained from the
      parents of the participants and from the respective school principals. Oral
      health examinations took place at the school under natural light, with
      participants seated on an ordinary chair/wheelchair. Dental caries examinations
      were carried out, using a mirror and wooden spatula in accordance with World
      Health Organisation (WHO) criteria and methods. Decayed, missing and filled
      primary and permanent teeth (dmft, DMFT) were recorded. All disabled individuals
      who were available during a screening period, were included. Those who were not
      available, as well as those whose health conditions could be compromised by
      dental examinations, were excluded. RESULTS: The number of decayed teeth ranged
      from 0-7 in children below 6 years, 0-12 in children below 11 years; and 0-17
      among young adults. The mean decay scores and the numbers of missing teeth
      increased with age. Only 3 (0.04%) individuals had dental fillings. The mean dmft
      score of children under 6 years was 5.51 (+/- 2.1), ranging from zero to 8. The
      mean DMFT's of the 11-18 and 19 years and older groups were 7.38 (+/- 3.22) and
      10.24 (+/- 2.97) respectively. CONCLUSIONS: Disabled individuals exhibited higher
      caries prevalence and unmet dental needs than the same age general population in
      Limpopo. Preventive measures and dental treatment should be considered urgent
      requirements at special needs schools in the Vhembe District.

PMID- 24660421
TI  - Periodontal disease: Mechanisms of infection and inflammation and possible impact
      on miscellaneous systemic diseases and conditions.
AB  - Periodontitis is a chronic inflammatory disease, resulting from a predominantly
      gram-negative microbial infection within the sub-gingival dental plaque biofilm.
      The resulting inflammatory response in the periodontal tissues may facilitate
      intravascular dissemination of micro-organisms and their products, throughout the
      body. The total surface area of this inflammatory field is estimated to be the
      size of the palm of the hand. A skin lesion of this size would prompt immediate
      medical intervention. However, the intra-oral (and similar-sized) infection is
      frequently ignored by health professionals, despite the fact that it may be
      associated with a range of systemic diseases/conditions.

PMID- 24660422
TI  - Glass-ionomer cements are not suitable for placing permanent posterior
      restorations--or are they?

PMID- 24660423
TI  - Oral medicine case book 55: odontogenic myxoma.

PMID- 24660424
TI  - Maxillo-facial radiology case 116. Hemangiopericytoma.

PMID- 24660425
TI  - The importance of communication between members of the dental team.

PMID- 24660426
TI  - Better data is essential to better care. Help the NHS obtain a complete care
      picture.

PMID- 24660427
TI  - We need to know more about A&E 'frequent flyers'.

PMID- 24660428
TI  - Monitor's plan to improve merger regime.

PMID- 24660429
TI  - Service design. Brand A&E: a solution to the crisis.

PMID- 24660430
TI  - Urgent care. Test drive the new care model.

PMID- 24660431
TI  - Integrated care. Everyone focused on the patient.

PMID- 24660432
TI  - 24/7 care. The seven day forecast.

PMID- 24660433
TI  - Workforce. 'I know my place'.

PMID- 24660434
TI  - Legal. Don't get caught by the latest act.

PMID- 24660436
TI  - Implants versus endodontics: "as the pendulum swings".

PMID- 24660435
TI  - Awaken the optimist!

PMID- 24660437
TI  - Focus on: interdisciplinary dentistry.

PMID- 24660438
TI  - Immediate dental implant placement: technique, part I.

PMID- 24660439
TI  - Implant-assisted unilateral removable partial dentures.

PMID- 24660440
TI  - Platelet-rich fibrin in mesh exposure repair.

PMID- 24660441
TI  - The failure rate: it's higher than you think!

PMID- 24660442
TI  - Nearly universal materials: materials and techniques designed to simplify
      clinical choices.

PMID- 24660443
TI  - Cosmetic gingivectomy using radiosurgery.

PMID- 24660444
TI  - The stress axis/DNA protocols in denture fabrication, part I.

PMID- 24660445
TI  - Treating a failing dentition: stable implant-supported removable restorations.

PMID- 24660446
TI  - New guaian-type sesquiterpene from Wikstroemia indica.
AB  - From a MeOH extract of powdered roots of Wikstroemia indica, we isolated a new
      guaian-type sesquiterpene (1) and two known guaian-type sesquiterpenes
      [oleodaphnal (2), 1alpha,7alpha,10alphaH-guaia-4,11-dien-3-one (3)], together
      with twelve known compounds: (+)-arctigenin, (+)-matairesinol, (+)-trachelogenin,
      (+)-nortrachelogenin, (+)-hinokinin, (+)-kusunokinin, 7-methoxycoumarin, 7
      hydroxycoumarin (umbelliferone), daphnogitin, daphnoretin, salicifoliol, and (-)
      pinoresinol. The structure of compound 1 was determined to be 4,10,11-guaiatrien
      3-one-14-oic acid, by the analyses of spectral data.

PMID- 24660447
TI  - Differences in the chemical composition of Arnica montana flowers from wild
      populations of north Italy.
AB  - The flower heads of fourteen wild Arnica montana L. populations were collected in
      the summer of 2010 in the provinces of Trento, Brescia and Bergamo (Italy). The
      dried flowers were analyzed to assess their chemical diversity. HLPC-MS analysis
      led to the identification of phenolic derivatives and sesquiterpene lactones in
      the samples, confirming literature data. Quali-quantitative analysis of the
      flower heads showed similar qualitative patterns both for the phenolic as well as
      sesquiterpene lactone derivatives, while significant variability was obtained in
      the amounts (HPLC-DAD) of sesquiterpene lactones (0.45-2.31%), phenolic acids
      (1.44-2.88%) and flavonoids (0.96-2.44%). The highest quantities of sesquiterpene
      lactones, flavonoids and phenolic acids were found in Malga Fregasoga (1703 m
      above sea level), Rifugio Camini (1608 m a.s.l.) and Malga Sass (1817 m a.s.l.)
      samples, respectively.

PMID- 24660448
TI  - A new dolabellane diterpenoid and a sesquilignan from Aglaia odorata var.
      microphyllina.
AB  - One new diterpenoid, 11alpha,12betaH-dolabella-4,8(17)-dien-3alpha,7beta,18-triol
      (1) and one new sesquilignan, 9-methoxy-7',8'-cis-7",8"-cis-buddlenol B (2),
      together with three known compounds, (+)-diasyringaresinol (3), N-methyl-5-
      hydroxy-delta3-pyrrolin-2-one (4) and marmin (5), have been isolated from Aglaia
      odorata var. microphyllina. Their structures were determined using 1D and 2D NMR
      spectroscopy. Compound 1 exhibited cytotoxic activity against the K562 cell line
      with an IC50 value of 12.5 microg/mL.

PMID- 24660449
TI  - New diterpenes from Azorella spinosa.
AB  - Two new diterpenes,2-acetoxy-13-hydroxy-mulin-11-ene and 2-acetoxy-mulin-11, 13
      diene,have been isolated from the aerial parts of Azorella spinosa and their
      structures determined by spectroscopic and conventional chemical methods.
      Furthermore, 2, 13-dihydroxy-mulin-11-ene was obtained using a basic hydrolysis
      of the first compound. Two diterpenes reported for other Azorella species have
      also been found, namely mulinolic acid and 13beta-hydroxyazorellane, as well as
      the triterpene lactone of ursolic acid,quercetin, and 7-hydroxycoumarin. The
      compounds were evaluated using antibacterial, antioxidant and enzymatic assays;
      no significant activity was detected.

PMID- 24660450
TI  - A new diterpenoid from the aerial parts of Andrographis paniculata.
AB  - One new and seven known diterpenoids were isolated from the aerial parts of
      Andrographis paniculata, and their structures elucidated on the basis of
      spectroscopic and spectrometric analysis, as well as chemical methods. The in
      vitro antiviral activities of these compounds against respiratory syncytial virus
      (RSV) were assayed.

PMID- 24660451
TI  - Isolation of a new anti-inflammatory 20, 21, 22, 23, 24, 25, 26, 27
      octanorcucurbitacin-type triterpene from Ibervillea sonorae.
AB  - A new cucurbitane-type triterpene, 20, 21, 22, 23, 24, 25, 26, 27
      octanorcucurbita-5-ene-3, 11, 16-trione (1), named kinoin D, was isolated from
      the roots of the medicinal plant Ibervillea sonorae, (wereque). The structure of
      1 was established on the basis of extensive NMR and MS studies. In addition, the
      known kinoins B (3) and C (5) were isolated, as were 16alpha-20,25-trihydroxy
      3alpha-(2-O-alpha-L-rhamnopyranosiyl-D-glucopyranosyloxy)-(10alpha)-cucurbit-5-en
      11,22-dione (6), (22S)-16alpha,22-diacetoxy-20,25-dihydroxy-3alpha-[3,4,6-tri-O
      acetyl-2-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-beta-glucopyranosyl]
      (10alpha)-cucurbita-5,23t-dien-11-one (7) and 16alpha-acetoxy-20,25-dihydroxy
      3alpha-[3,4,6-tri-O-acetyl-2-O-(2,3,4,-tri-O-acetyl-alpha-L-rhamnopyranosyl)-beta
      D-glucopyranosyl]-(10alpha)-cucurbita-5-ene-11,22-dione (8). Compound 1 exhibited
      anti-inflammatory activity in TPA-induced edema in mice.

PMID- 24660452
TI  - Determination of triterpenic acids and screening for valuable secondary
      metabolites in Salvia sp. suspension cultures.
AB  - Plant in vitro cultures are a prospective alternative for biochemicals
      production, for example the triterpenes oleanolic and ursolic acid present in
      plants and cell cultures of Salvia sp. Our objective was to develop a suitable
      analysis protocol for evaluation of triterpenic acid yield in plant raw material
      and in vitro cultures supporting selection processes. Moreover, valuable
      bioactive compounds had to be revealed. Thus, different strategies enhancing the
      separation for a sensitive and effective HPLC-UV method were investigated and the
      developed method was validated for linearity, precision, accuracy, limits of
      detection and quantification. A baseline separation of these isomers enabled
      detection limits of below 0.4 microg/mL and quantification limits of about 1.2
      microg/mL. Over the tested concentration range a good linearity was observed (R2
      > 0.9999). The variations in the method were below 6% for intra- and inter-day
      assays of concentration. Recoveries were between 85-98% for both compounds using
      ethanol as extraction solvent. Additionally, metabolite profiling of cell
      suspension culture extracts by GC-MS has shown the production variability of
      different plant metabolites and especially the presence of plant phenols and
      sterols. These studies provide a method suitable for screening plant and cell
      culture productivity of triterpenic acids and highlighted interesting co-products
      of plant cell cultures.

PMID- 24660453
TI  - Inhibitory effect of the plant Clusia fluminensis against biological activities
      of Bothrops jararaca snake venom.
AB  - The ability of extracts of the plant Clusia fluminensis Planch & Triana
      (Clusiaceae Lindl.) to neutralize proteolysis, clotting, hemolysis, hemorrhagic
      and lethality activities of Bothrops jararaca snake venom was studied. Clusianone
      and lanosterol from the flower and fruit extracts, respectively, were also
      tested. The extracts of different organs of C. fluminensis inhibited proteolysis
      and hemolysis induced by B. jararaca venom, but with different potencies. Only
      the stems prevented blood clotting. Only the acetone extract of the fruit
      protected mice from hemorrhage while the acetone or methanol extracts prevented
      mice from death. Clusianone and lanosterol did not inhibit clotting or
      hemorrhage, but the former inhibited proteolysis and the latter hemolysis.

PMID- 24660454
TI  - Chiral resolution and absolute configuration of 3alpha,6beta
      dicinnamoyloxytropane and 3alpha,6beta-di(1-ethyl-1H-pyrrol-2
      ylcarbonyloxy)tropane, constituents of Erythroxylum species.
AB  - Chiral resolution of (+/-)-3alpha,6beta-dicinnamoyloxytropane (1) and (+/-)
      3alpha,6beta-di(1-methyl-1H-pyrrol-2-ylcarbonyloxy)tropane (2), prepared by
      esterification of (+/-)-3alpha,6beta-tropanediol (3), was achieved using an
      amylose-derived HPLC stationary phase and normal phase conditions. The
      corresponding vibrational circular dichroism (VCD) spectra provided the absolute
      configuration of the enantiomers as (-)-(3R,6R)-1, (+)-(3S,6S)-1, (-)-(3R,6R)-2
      and (+)-(3S,6S)-2. In each case, characteristic VCD bands for the absolute
      configuration determination of the 3alpha,6beta-tropandiol esters were observed.
      While the absolute configuration of natural 1, previously isolated from
      Erythroxylum hypericifolium, could not be established due to the lack of
      literature optical rotation values, that of catuabine E, previously isolated from
      E. vacciniifolium, is now assigned as (-)-(3R,6R)-2 by comparison with the
      optical rotation values of the prepared samples and the reported rotation of the
      natural product.

PMID- 24660455
TI  - Aporphine alkaloids of Cinnamomum mollissimum and their bioactivities.
AB  - A chemical investigation of the crude extracts of Cinnamomum mollissimum bark
      resulted in the isolation of five aporphine alkaloids, namely N-methyl-1,2,10
      trimethoxyaporphine, N-methylhernagine, N-methylhemovine, hernagine and
      hernovine. Their structures were elucidated by spectral analysis. The alkaloid
      crude extract demonstrated significant antibacterial and antioxidant activities.

PMID- 24660456
TI  - Antifungal activity of metabolites from the marine sponges Amphimedon sp. and
      Monanchora arbuscula against Aspergillus flavus strains isolated from peanuts
      (Arachis hypogaea).
AB  - Contamination of preharvest and stored peanuts (Arachis hypogaea L.) by
      aflatoxigenic strains of Aspergillus flavus is an important economical and food
      safety problem in many tropical and subtropical areas of the world. The present
      investigation reports the antifungal activity of a halitoxins/amphitoxins
      enriched extract obtained from the sponge Amphimedon sp. (HAEEAsp), and of
      batzelladine L isolated from the sponge Monanchora arbuscula on Aspergillus
      flavus isolated from stored peanuts. A PCR system directed against the ITS region
      and aflatoxin biosynthetic pathway genes of A. flavus was applied for
      identification of aflatoxin producing strains. The HAEEAsp extract and
      batzelladine L showed minimal inhibitory concentration (MIC) in the range between
      1.9 to 15.6 microg/mL and between 1.9 to 7.8 microg/mL, respectively. The minimal
      fungicide concentration (MFC) of HAEEAsp extract and batzelladine L was in the
      range between 3.9 to 31.3 microg/mL and 3.9 to 15.6 microg/mL, respectively.
      These results indicate that these marine alkaloids may be further explored for
      the development of potential lead compounds active against aflatoxigenic fungi.

PMID- 24660457
TI  - Synthesis of sepiapterin-C via hydrolysis of 6-ethynylpteridine.
AB  - Acid hydrolysis of 6-ethynylpteridine catalyzed by mercury oxide gives 6-acetyl-2
      amino-3,4-dihydropteridin-4-one in good yield. Partial reduction of the product
      with dissolved Al in NH3 solution afforded sepiapterin-C.

PMID- 24660458
TI  - Flavonoids produced by tissue culture of Dracaena cambodiana.
AB  - Dragon's blood is a traditional medicine used in many countries of many cultures
      because of its various therapeutic uses, and its main bioactive compounds are
      flavonoids, which mainly exhibit antitumor and antimicrobial activities. In the
      process of tissue culture of Dracaena cambodiana, one of its resource plants, red
      secretion was discovered in the culture when 6-benzylaminopurine was added.
      Analysis of its constituents by HPLC in comparison with dragon's blood and the
      standards proved that 17 compounds, including 10 flavonoids, are the same as
      those in dragon's blood. It is promising that flavonoids from dragon's blood
      could be produced by tissue culture of its resource plants for the development of
      new drugs.

PMID- 24660459
TI  - Determination of catechins from Elephantorrhiza elephantina and Pentanisia
      prunelloides using voltammetry and UV spectroscopy.
AB  - In this work, we report the identification and quantification of catechins by
      electrochemistry and UV-Vis spectroscopy in Elephantorrhiza elephantina
      (Fabaceae) and Pentanisia prunelloides (Rubiaceae), both of which are medicinal
      plants that are widely used in Southern Africa to remedy various ailments. A
      comparative study of the catechin content as (-)-epicatechin equivalent is
      reported for the first time, with E. elephantina exhibiting a higher
      concentration relative to P. prunelloides in both aqueous and methanol extracts.

PMID- 24660460
TI  - In vitro antioxidant activity, phenolic compounds and protective effect against
      DNA damage provided by leaves, stems and flowers of Portulaca oleracea
      (Purslane).
AB  - This study analyzed the antioxidant properties of Portulaca oleracea L., known as
      purslane. The samples (leaves, flowers and stems) were collected at two different
      locations in Portugal: Tavira (L1) and Vendas Novas (L2). Assays for total
      antioxidant activity, total phenolic content and ferric-reducing antioxidant
      power were conducted and, for both locations, significantly higher values (P <
      0.05) were observed for stems (508.8 and 982.3 mg AAE/100 g DW, 1008.6 and 2285.5
      mg GAE/100 g DW, 121.0 and 166.3 mg TE/100 g DW, respectively for each location),
      than in leaves or flowers. In the DPPH assay, the three-plant parts from L2
      reached the 50% inhibition rate in lower concentrations than plants from L1. On
      the other hand, higher concentrations of total monomeric anthocyanins were found
      in samples from L1 (95.5, 88.8 and 86.0 mg/L) than in samples from L2 (81.7, 70.5
      and 59.8 mg/L). The same was true for phenolic acids, estimated by liquid
      chromatography, where methanol extracts were used. Phenolic extracts from all
      three-plant parts from both locations showed protective effects on DNA against
      hydroxyl radicals. This work suggests the possibility of benefit to human health
      from its consumption, related to the high antioxidant activity of purslane, even
      the stems, usually discarded in daily consumption.

PMID- 24660461
TI  - In vitro antiviral activity of a series of wild berry fruit extracts against
      representatives of Picorna-, Orthomyxo- and Paramyxoviridae.
AB  - Wild berry species are known to exhibit a wide range of pharmacological
      activities. They have long been traditionally applied for their antiseptic,
      antimicrobial, cardioprotective and antioxidant properties. The aim of the
      present study is to reveal the potential for selective antiviral activity of
      total methanol extracts, as well as that of the anthocyanins and the non
      anthocyanins from the following wild berries picked in Bulgaria: strawberry
      (Fragaria vesca L.) and raspberry (Rubus idaeus L.) of the Rosaceae plant family,
      and bilberry (Vaccinium myrtillis L.) and lingonberry (Vaccinium vitis-idaea L)
      of the Ericaceae. The antiviral effect has been tested against viruses that are
      important human pathogens and for which chemotherapy and/or chemoprophylaxis is
      indicated, namely poliovirus type 1 (PV-1) and coxsackievirus B1 (CV-B1) from the
      Picornaviridae virus family, human respiratory syncytial virus A2 (HRSV-A2) from
      the Paramyxoviridae and influenza virus A/H3N2 of Orthomyxoviridae. Wild berry
      fruits are freeze-dried and ground, then total methanol extracts are prepared.
      Further the extracts are fractioned by solid phase extraction and the non
      anthocyanin and anthocyanin fractions are eluted. The in vitro antiviral effect
      is examined by the virus cytopathic effect (CPE) inhibition test. The results
      reveal that the total extracts of all tested berry fruits inhibit the replication
      of CV-B1 and influenza A virus. CV-B1 is inhibited to the highest degree by both
      bilberry and strawberry, as well as by lingonberry total extracts, and influenza
      A by bilberry and strawberry extracts. Anthocyanin fractions of all wild berries
      strongly inhibit the replication of influenza virus A/H3N2. Given the obtained
      results it is concluded that wild berry species are a valuable resource of
      antiviral substances and the present study should serve as a basis for further
      detailed research on the matter.

PMID- 24660462
TI  - Induction of apoptosis and cell cycle arrest in human colon carcinoma cells by
      Corema album leaves.
AB  - The leaves of Corema album (Ericaceae), an endemic shrub which grows in Atlantic
      coastal areas of the Iberian Peninsula, are rich in flavonoids and other
      secondary metabolites. Silica gel column chromatography of the ethyl acetate
      extract from dried leaves was performed and a flavonic active fraction was
      obtained. The cytotoxic activity of this fraction was assessed using the colon
      cancer cell lines HCT116 and HT29. After 48 hours of treatment, cell viability
      was determined with luminescence-based ATPLite assay, showing IC50 values of 7.2
      +/- 0.7 and 6.8 +/- 1.2 microg/mL, respectively. The study by flow cytometry
      revealed that the cytotoxicity of this fraction was mediated, at least in part,
      by induction of apoptosis and G2/M cell cycle arrest. The active fraction was
      then subjected to Sephadex LH-20 chromatography and two flavonoids were separated
      and identified as the flavanone pinocembrin and 2',4'-dihydroxychalcone after UV,
      MS and NMR analysis.

PMID- 24660463
TI  - How to deal with nomenclatoral ambiguities of trivial names for natural products?
      -a clarifying case study exemplified for "corymbosin".
AB  - Many names of plant secondary compounds that have been isolated and identified in
      the course of phytochemical investigations are based either on the vernacular or
      Latin names of the source plants, are constructed according to rules of chemical
      nomenclature, or consist of in-between forms. Trivial names, based on the
      specific epithets of biological organisms, occasionally create confusion because
      such epithets are used in numerous combinations and, therefore, could potentially
      be used when naming chemical entities from radically different sources. Such an
      example of ambiguous naming is represented with the case of corymbosin, a name
      that was assigned to two chemically distinct compounds that were isolated and
      reported simultaneously in 1967 from two different spermatophyte taxa: a terpene
      glucoside from Turbina corymbosa and a flavone from Webera corymbosa. The flavone
      is more widespread and has been reported so far from 15 taxa, whereas the
      glucoside has thus far only been isolated from the original source species.
      Furthermore, glycosides named corymbosins K1-K4 were isolated in 2006 from Knoxia
      corymbosa. This article emphasizes the need to adhere to strict principles when
      naming secondary constituents and suggests that a practice should be applied that
      is similar to the application of the priority rules used in botanical
      nomenclature for homonyms. The use of the trivial name, corymbosin, should be
      applied only to the more widespread tricetin-7,3',4',5'-tetramethyl ether by
      rules of conservation.

PMID- 24660464
TI  - Chromatographic analysis and antioxidant capacity of Tabernaemontana
      catharinensis.
AB  - In this study we evaluated the composition of the crude extract and fractions of
      Tabernaemontana catharinensis (Apocynaceae) by HPLC/DAD and GC/MS. We also tested
      the antioxidant capacity and investigated the contents of polyphenols,
      flavonoids, tannins and alkaloids of T. catharinensis stem bark. The extract and
      fractions showed inhibition against thiobarbituric acid reactive species (TBARS),
      in the following order: ethyl acetate (IC50 = 4.7 +/- 0.2 microg/mL) >
      dichloromethane (23.9 +/- 1.1 microg/mL) > n-butanolic (25.2 +/- 0.4 microg/mL) >
      crude extract (38.0 +/- 0.07 microg/mL). Moreover, the DPPH assay, presented IC50
      values ranged from 5.6 +/- 0.6 to 30.3 +/- 1.3 microg/mL. Contents of total
      phenols, flavonoids, tannins and alkaloids of T. catharinensis followed the
      order: ethyl acetate > n-butanolic > dichloromethane fractions > crude extract.
      HPLC/DAD analyses indicated that gallic, chlorogenic and caffeic acids, and
      rutin, quercetin and kaempferol are components of the species. Taken together,
      the results suggest that T. catharinensis could be considered an effective agent
      in the prevention of diseases associated with oxidative stress.

PMID- 24660465
TI  - Simultaneous determination of 13 chemical marker compounds in Gwakhyangjeonggi
      san, a herbal formula, with validated analytical methods.
AB  - This study was designed for simultaneous determination of 13 chemical marker
      compounds, namely, protocatechuic acid, chlorogenic acid, caffeic acid,
      liquiritin, hesperidin, apigetrin, rosmarinic acid, oxypeucedanin hydrate,
      byakangelicin, apigenin, glycyrrhizin, nobiletin, and 6-gingerol in
      Gwakhyangjeonggi-san (GJS: Huoxiang-zhengqi-san in Chinese). A quantitative
      analytical method was developed based on HPLC-PDA with validation in terms of
      precision, accuracy, and repeatability, and successfully employed for quality
      evaluation of GJS samples with the help of chemometric techniques such as
      principal component analysis (PCA) and hierarchical clustering analysis (HCA).
      The correlation coefficient for the linear regression was > 0.9994. The intra-day
      and inter-day precision was < 3.0% of the relative standard deviation (RSD)
      value, and the recovery was in the range 92.5-107.0%, with RSD values < 4.0%, and
      the repeatability was < 3.0% of RSD. Variations in the quantity were observed in
      GJS products from different origins, which were classified by PCA and HCA. The
      quantitative and chemometric analyses indicate the necessity for consistency in
      GJS production for the purpose of quality control.

PMID- 24660466
TI  - Single crystal X-ray diffraction, spectroscopic and mass spectrometric studies of
      furanocoumarin peucedanin.
AB  - The structure of peucedanin, isolated from Peucedanum tauricum Bieb. (Apiaceae),
      has been established using single crystal X-ray diffraction. This furanocoumarin
      isolated from the light petroleum extract of P. tauricum fruits was characterized
      by high resolution EI-MS, sATR-FTIR and 2D NMR spectroscopic techniques. The EI
      MS showed the typical fragmentation pattern of methoxyfuranocoumarins. Extensive
      1D (1H and 13C) as well as 2D NMR data enabled complete assignment of the carbon
      atoms in the peucedanin molecule. The FTIR data confirms intermolecular hydrogen
      bonding between peucedanin molecules in polar solvents. Peucedanin crystallises
      in the R-3 space group from the trigonal system with one molecule in the
      asymmetric part of the unit cell. The crystal lattice of peucedanin consists of
      the molecules arranged in separate columns. They are related by two fold screw
      axes and centres of symmetry. Interestingly, peucedanin columns form two channels
      per unit cell with a diameter of 7.5angstrom going through the crystal lattice in
      the Z-direction. These channels are filled with disordered water molecules, which
      are surrounded by hydrophobic methyl groups and are located exactly at the
      centres of the channels. The peucedanin molecules are stacked in a single column
      with the opposite orientation of the neighbouring molecules. These results could
      be interesting in further application of this molecule, for example in biological
      tests of its activity.

PMID- 24660467
TI  - 8-hydroxycudraxanthone G suppresses IL-8 production in SP-C1 tongue cancer cells.
AB  - Production of IL-8 primarily promotes angiogenic responses in cancer cells, which
      lead to favorable disease progression. Suppressing this production may,
      therefore, be a significant therapeutic intervention in targeting tumor
      angiogenesis. This study aimed to evaluate the reduction effects of xanthones in
      cancer cell lines. Nine known prenylated xanthones (1-9), isolated from the
      pericarp of Garcinia mangostana Linn (GML), were tested for their ability to
      suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell
      line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48
      hours. This is the first report of 8-hydroxycudraxanthone G suppressing the
      production of IL-8 (45% at 15.7 microg/mL in 48 hours). These results suggest
      that the prolonged suppression of IL-8 production by cancer cell lines is
      concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

PMID- 24660468
TI  - Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute
      configuration.
AB  - From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma
      butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin
      (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)
      hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl
      gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)
      arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated
      from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of
      the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in
      nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)
      absolute configuration showed preferential cytotoxicity. On the other hand, three
      lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential
      cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82,
      and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin
      was evaluated against the activation of Akt, which is a key process in the
      tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*)
      strongly suppressed the activation of Akt. These results indicate that the
      (2R,3R)-absolute configuration of (-)-enantiomers should be required for the
      preferential cytotoxicity through the inhibition of Akt activation.

PMID- 24660469
TI  - Antiplatelet aggregation effects of phenanthrenes from Calanthe arisanensis.
AB  - Three phenanthrenes (1-3), four indole alkaloids (4-7) and one steroid (8) were
      isolated from the leaves of Calanthe arisanensis for the first time. In the
      antiplatelet aggregation assay, phenanthrenes 1 and 2 showed potential
      antiplatelet activity. We have reported and discussed here the antiplatelet
      aggregation properties of the eleven naturally-occurring phenanthrenes (1-2 and 9
      17) isolated from the underground part of the plant and eighteen chemically
      synthesized phenanthrenes (18-35). Overall, our data demonstrated that 1,4
      phenanthrenequinones 20, 21 and 22 (collagen, IC50 0.2, 0.2, 0.1 microg/mL;
      thrombin, IC50 0.8, 1.0, 1.1 microg/mL, respectively) could be promising lead
      candidates for further cardiovascular disease studies.

PMID- 24660470
TI  - In vivo anti-inflammatory activity of some naturally occurring O- and N-prenyl
      secondary metabolites.
AB  - A series of O- and N-prenyl secondary metabolites of insect, fungal, and plant
      origin have been evaluated for their topical anti-inflammatory activity using the
      Croton oil ear test in mice as a model of acute inflammation. Some of the tested
      compounds revealed an effect (ID50 = 0.31 divided by 0.56 micromol/cm2)
      comparable with that of the reference non-steroidal anti-inflammatory drug
      indomethacin (ID50 = 0.23 micromol/cm2).

PMID- 24660471
TI  - Phomopsolides and related compounds from the alga-associated fungus, Penicillium
      clavigerum.
AB  - For the past fifteen years we have studied the secondary metabolites of
      extremophilic fungi from the Berkeley Pit, an abandoned acid mine waste lake.
      Fungi associated with an acid-tolerant alga have also been harvested from the
      Pit. Penicillium clavigerum Demelius was isolated from the green alga Chlorella
      vulgaris Beyerinck [Beijerinck]. In culture it produced the known compounds
      phomfuranone (1), patulin (2), dimethylphthalides (3) and (4), phomopsolide A
      (5), phomopsolide C (6), phomopsolide B (7), phomopsolide E (8), phomopsolide F
      (9), and phompyrone (10) and the new compound berkbenzofuran thioester (11).
      Compounds 5 and 6 were potent inhibitors (IC50 < 10 microM) of specific and
      established human cancer cell lines.

PMID- 24660472
TI  - Qualitative identification of dibenzoylmethane in licorice root (Glycyrrhiza
      glabra) using gas chromatography-triple quadrupole mass spectrometry.
AB  - Licorice root (Glycyrrhiza glabra), an herbal Chinese medicine, has shown
      medicinal uses in therapeutics and cancer prevention. Dibenzoylmethane (DBM; 1, 3
      diphenyl-1, 3-propadinedione), a small beta-diketone, has been reported to be a
      minor constituent of licorice and a known deregulator of the human prostate
      cancer cell cycle. Characterization of the phytochemical profiles of licorice
      root forms including commercially available DBM will advance our search in
      identifying novel reagents for prostate cancer therapeutics. Gas chromatography-
      triple quadrupole-mass spectrometric analysis was used for detecting DBM in
      licorice root extracts. DBM and all licorice forms exhibited a component with a
      retention time of 14.5 minutes. The major fragment ions detected were at m/z 77,
      105, 147, 223 and 224 at the identified retention time by selected reaction
      monitoring/SRM. These data confirm the presence of DBM from its natural source
      (G. glabra), and the GC-MS/SRM method helps in the identification of this minor
      component in a complex biological matrix.

PMID- 24660473
TI  - Anti-L. donovani activity in macrophage/amastigote model of palmarumycin CP18 and
      its large scale production.
AB  - Palmarumycin CP18, isolated from an extract of the fermentation broth and
      mycelium of the Panamanian endophytic fungus Edenia sp., was previously reported
      with strong and specific activity against Leishmania donovani. Here we report
      that when the same strain was cultured on different solid media--Harrold Agar,
      Leonian Agar, Potato dextrose Agar (PDA), Corn Meal Agar, Honey Peptone Agar, and
      eight vegetables (V8) Agar--in order to determine the optimal conditions for
      isolation of palmarumycin CP18, no signal for this compound was observed in any
      of the 1H NMR spectra of fractions obtained from these extracts. However, one
      extract, prepared from the fungal culture in PDA contained significant amounts of
      CJ-12,372, a possible biosynthetic precursor of palmarumycin CP18. Edenia sp. was
      cultivated on a large scale on PDA and CJ-12,372 was converted to palmarumycin
      CP18 by oxidation of its p-hydroquinone moiety with DDQ in dioxane. Palmarumycin
      CP18 showed anti-leishmanial activity against L. donovani in a
      macrophage/amastigote model, with IC50 values of 23.5 microM.

PMID- 24660474
TI  - Medelamine C, a new omega-hydroxy alkylamine derivative from endophytic
      Streptomyces sp. YIM 66142.
AB  - A new alkylamine derivative and a common fatty acid were isolated from
      Streptomyces sp. YIM 66142. On the basis of spectral data, including HRMS, NMR
      and 2D NMR, their structures were determined as medelamine C (1) and isomyristic
      acid (2). The omega-hydroxyl group in structure 1 is rare in a natural
      alkylamine. The possible biosynthetic pathway in the genus Streptomyces from
      isomyristic acid (2) to medelamines is proposed. Compound 1 showed no obvious
      cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, SW480 cell lines. The omega
      hydroxyl and the acetyl at NH in compound 1 decreased its cytotoxicity in
      comparison with that of medelamine.

PMID- 24660475
TI  - Enzyme-treated Asparagus officinalis extract shows neuroprotective effects and
      attenuates cognitive impairment in senescence-accelerated mice.
AB  - Increases in the number of patients with dementia involving Alzheimer's disease
      (AD) are seen as a grave public health problem. In neurodegenerative disorders
      involving AD, biological stresses, such as oxidative and inflammatory stress,
      induce neural cell damage. Asparagus (Asparagus officinalis) is a popular
      vegetable, and an extract prepared from this reportedly possesses various
      beneficial biological activities. In the present study, we investigated the
      effects of enzyme-treated asparagus extract (ETAS) on neuronal cells and early
      cognitive impairment of senescence-accelerated mouse prone 8 (SAMP8) mice. The
      expression of mRNAs for factors that exert cytoprotective and anti-apoptotic
      functions, such as heat-shock protein 70 and heme oxygenase-1, was upregulated in
      NG108-15 neuronal cells by treatment with ETAS. Moreover, when release of lactate
      dehydrogenase from damaged NG108-15 cells was increased for cells cultured in
      medium containing either the nitric oxide donor sodium nitroprusside or the
      hypoxia mimic reagent cobalt chloride, ETAS significantly attenuated this cell
      damage. Also, when contextual fear memory, which is considered to be a
      hippocampus-dependent memory, was significantly impaired in SAMP8 mice, ETAS
      attenuated the cognitive impairment. These results suggest that ETAS produces
      cytoprotective effects in neuronal cells and attenuates the effects on the
      cognitive impairment of SAMP8 mice.

PMID- 24660476
TI  - Anticancer activity of binary toxins from Lysinibacillus sphaericus IAB872
      against human lung cancer cell line A549.
AB  - The inhibitory effect of binary toxic (Bin) protein produced by Lysinibacillus
      sphaericus IAB872 on cell proliferation of human lung, liver, stomach and
      cervical tumor cell lines was assessed using MTT assay. The effect of Bin protein
      on A549 cell proliferation, apoptosis, cell cycle, migration and invasion were
      examined by MTT assay, Western blotting, Immunocytochemical staining, flow
      cytometry assay and wound-healing assay. Results showed that Bin protein inhibits
      proliferation of a range of human cancer cells in vitro. The anti-proliferative
      effect of Bin is associated with cell apoptosis as a result of an increased ratio
      of cellular Bax/bcl-2, up-regulated CyclinB1 and down-regulated Cdc25c
      expression, and its anti-proliferative action was associated with cell cycle
      arrest in the G2/M-phase. Bin protein could promote apoptosis and inhibit
      motility and invasion of A549 cancer cells. The anti-proliferative effect of Bin
      protein was associated with the induction of apoptotic cell death and cell cycle
      disruption. These results show that Bin protein has the potential to be developed
      as a chemotherapeutic agent by induction of human tumor cell apoptosis.

PMID- 24660477
TI  - The use of cycleave PCR for the differentiation of the rejuvenating herb species
      Pueraria candollei (White Kwao Khruea), Butea superba (Red Kwao Khruea), and
      Mucuna macrocarpa (Black Kwao Khruea), and the simultaneous detection of multiple
      DNA targets in a DNA admixture.
AB  - Kwao Khruea, the tuberous roots of Pueraria candollei Graham ex Benth. (White
      Kwao Khruea), Butea superba Roxb. (Red Kwao Khruea), and Mucuna macrocarpa Wall.
      (Black Kwao Khruea), are used as rejuvenating herbs in traditional medicine in
      many tropical countries. Although Kwao Khruea has attracted strong interest
      because of its rejuvenation properties, each species is used for specific
      purposes and effects. P. candollei shows estrogenic effects in females. In
      contrast, B. superba and M. macrocarpa show androgenic effects in males. The
      potential misidentification of dried tuberous roots of various Kwao Khruea
      species might cause problems in the drug market, especially when they are reduced
      into powders. A cycleave PCR, which is based on the sequence of chloroplast matK
      gene, was developed to differentiate P. candollei, B. superba, and M. macrocarpa.
      The results showed that cycleave PCR is able to identify specific Kwao Khruea
      species. A multiplex cycleave PCR was optimized for the simultaneous detection of
      two different DNA targets in a DNA admixture. The specificity of this technique
      was confirmed by its ability to distinguish M. macrocarpa from five related
      Mucuna species. Cycleave PCR can be a specific, sensitive, and rapid method for
      the identification of medicinal plants and crude plant samples.

PMID- 24660478
TI  - Chemical compositions and antimicrobial activity of the essential oils of
      Hornstedtia havilandii (Zingiberaceae).
AB  - The chemical compositions and antimicrobial activity of the fresh rhizome and
      flower oils of Hornstedtia havilandii were studied. The components present were
      analyzed using GC and GC-MS. A total of forty-eight constituents were
      successfully identified from the flower and rhizome oils, representing 93.4% and
      89.6%, respectively. The most abundant components of the flower oil were beta
      pinene, (19.5%), beta-elemene, (10.0%), beta-cubebene, (6.2%), alpha-pinene,
      (5.6%), gamma-cadinene, (4.3%) and germacrene D, (3.3%), while alpha-copaene,
      (10.2%), beta-selinene, (8.4%), beta-elemene, (7.0%), gamma-cadinene, (6.9%),
      beta-cubebene, (5.3%) and germacrene D, (5.3%) were found as the main components
      of the rhizome oil. The essential oils were tested for antimicrobial activity
      against Gram-positive bacteria, Gram-negative bacteria and yeasts. Both oils
      showed activity against the Gram-positive bacterium, Staphylococcus aureus, with
      moderate MIC values of 112.5 micro/mL, however, for Gram-negative bacteria, the
      flower oil showed weak antimicrobial activity with a MIC value of 225 microg/mL.
      Only very weak activity was shown against the yeasts Candida albicans and C.
      glabrata, with MIC values of 900-1800 microg/mL.

PMID- 24660479
TI  - Chemical composition, antioxidant and antimicrobial activity of essential oil and
      extracts of Tragopogon graminifolius, a medicinal herb from Iran.
AB  - Tragopogon graminifolius DC., family Compositae, is widely consumed as a green
      vegetable in the west of Iran and for the treatment of gastrointestinal and
      hepatic ailments. In this study, the chemical composition of the essential oil
      from T. graminifolius aerial parts was evaluated by gas chromatography and gas
      chromatography mass spectrometry. Moreover, antioxidant and antimicrobial
      activity of the essential oil and various extracts of T. graminifolius were
      determined. Fifty-eight compounds representing 87.2% of the essential oil were
      identified. The main components were n-hexadecanoic acid (22.0%), beta
      caryophyllene (7.5%), heneicosane (6.6%), and nonanal (5.2%). The essential oil
      demonstrated the highest DPPH radical scavenging activity (56.6 +/- 8.8 ug/mL)
      and the 80% ethanolic extract the highest ferric reducing antioxidant activity
      (908.2 +/- 79.5 mmol Fe2+ ion/g extract). The total phenolic content of the 80%
      ethanolic extract from the aerial parts was the highest (560.7 +/- 18.8 mg/g
      gallic acid equivalent). In the antimicrobial test, Shigella dysenteriae was the
      most vulnerable microorganism, followed by Proteus vulgaris, and the essential
      oil exhibited the highest antibacterial activity among the samples. The results
      indicated that the essential oil and extracts of T. graminifolius could be
      consumed as a natural herbal preservative or complementary supplement in the food
      and pharmaceutical industries.

PMID- 24660480
TI  - Antinociceptive and anti-edematous activities of the essential oils of two Balkan
      endemic Laserpitium species.
AB  - In this paper antinociceptive and anti-edematous effects are examined of the
      essential oils of the underground parts of two Balkan endemic Laserpitium species
      (Apiaceae), L. zernyi and L. ochridanum. Furthermore, the essential oil of the
      underground parts of L. ochridanum is chemically characterised by GC and GC-MS.
      Antinociceptive and anti-edematous effects were measured in a rat model of
      localized inflammation, induced by carrageenan, using apparatus for the modified
      paw-pressure test, and plethysmometer, respectively. The effects of both
      Laserpitium essential oils were measured after oral gavage administration to male
      Wistar rats in doses of 25, 50 and 100 mg/kg. The main constituents of L.
      ochridanum essential oil were: alpha-pinene (33.2%), alpha-bisabolol (10.3%) and
      chamazulene (14.9%). The essential oil of L. zernyi was previously shown to be
      rich in alpha-pinene (31.6%) and alpha-bisabolol (30.9%). Both examined essential
      oils produced a significant dose-dependent antinociceptive effect. The
      corresponding ED50 +/- SEM in producing antinociception were 45.9 +/- 4.9 mg/kg
      and 42.4 +/- 2.1 mg/kg for L. zernyi and L. ochridanum oil, respectively. Both
      essential oils also significantly reduced paw edema in a dose-dependent manner.
      The estimated ED50 +/- SEM values for the anti-edematous effect were 36.3 +/- 4.5
      mg/kg for L. zernyi oil and 45.1 +/- 11.3 mg/kg for L. ochridanum oil. These
      results suggest that the essential oils of both investigated Laserpitium species
      may be effective against pain and edema present in various inflammatory
      conditions.

PMID- 24660481
TI  - Chemical composition of the essential oil from Croton kimosorum, an endemic
      species to Madagascar.
AB  - Croton kimosorum Leandri is an endemic species to Madagascar. The chemical
      composition of aerial parts, leaf and stem oils is reported for the first time.
      Analysis was carried out by combination of chromatographic (CC, GC),
      spectroscopic and spectrometric (MS, 13C NMR) techniques. In total, 76 compounds
      have been identified. Essential oil isolated from aerial parts contained mainly
      linalool (21.6%), sabinene (10.4%), 1,8-cineole (6.3%), beta-pinene (6.2%), (E)
      beta-caryophyllene (5.9%), terpinen-4-ol (4.8%), geraniol (4,5%) and germacrene D
      (2.3%). In comparison with the first sample, the composition of leaf and stem
      oils varied slightly, while essential oil isolated by vapor distillation from a
      semi-industrial still exhibited similar composition.

PMID- 24660483
TI  - Volatile organic compounds of six French Dryopteris species: natural odorous and
      bioactive resources.
AB  - Aerial parts of six Dryopteris species collected in France were investigated for
      volatile organic compounds (VOC) for the first time. Fifty-three biosynthesized
      VOC from the shikimic, lipidic and terpenic pathways were identified using gas
      chromatography/mass spectrometry. Many bioactive polyketide compounds as
      filicinic derivatives (from 8.5 to 23.5%) and phloroglucinol derivatives (from
      8.2 to 53.8%) with various pharmacological activities were detected in high
      amount from five analysed Dryopteris species, in particular D. oreades and D.
      borreri, i.e., propionylfilicinic acid (> 10% in D. affinis and D. ardechensis)
      and 2,6-dihydroxy-4-methoxy-3-methylbutyrophenone (aspidinol) (19.1% and 14.6% in
      D. oreades and D. borreri, respectively). Several terpenic derivatives with a low
      odor threshold were identified, i.e., carota-5,8-diene (from 2.5 to 18.4%:
      floral, woody or fresh bark note), (E)-nerolidol (> 10% for D. borreri and D.
      cambrensis; floral or woody odor), alpha-selinene (> 7% for D. ardechensis; woody
      spicy odor), and aristolene (12.8% in D. affinis; flower, sweet odor). The main
      isoprenoid derivatives were 4-hydroxy-5,6-epoxyionol, 3-oxo-alpha-ionol and 4-oxo
      7,8-dihydro-beta-ionone (essentially in D. remota), whereas the main aromatic
      compound was 4-hydroxy-3-methoxyacetophenone (20.6% and 12.6% in D. cambrensis
      and D. borreri, respectively) and the main lipid derivative was 1-octen-3-ol with
      a mushroom-like odor (from 0.4 to 8.3%). Dryopteris species resources are of
      great interest as a reservoir of odorous and bioactive compounds.

PMID- 24660482
TI  - Intraspecific variability of the essential oil of Cladanthus mixtus from Morocco.
AB  - Air-dried aerial parts of wild Cladanthus mixtus were collected from two
      different regions of Morocco, Bouznika and Oujda, during 2011 and 2012. Forty
      individual plant samples were hydrodistilled using a Clevenger apparatus and the
      obtained essential oils were analyzed by GC and GC/MS. The yield obtained varies
      greatly with a range of 0.3 to 0.8%. The chemical composition of C. mixtus oils
      changes from one region to another. A total of 53 constituents were identified.
      To the best of our knowledge, two chemotypes were defined for the first time for
      this species in the regions studied. 2-Methyl-2-trans-butenyl methacrylate (32.8
      35.2%) / ar-curcumene (13-14%) characterize the chemotypeof the C. mixtus plants
      from Bouznika, and trans-beta-farnesene (35.5-50.3%) the chemotype from Oujda.

PMID- 24660484
TI  - Essential oil compositions of two populations of Salvia samuelssonii growing in
      different biogeographical regions of Jordan.
AB  - The composition of the essential oils of flowering aerial parts of Salvia
      samuelssonii Rech. fil. (Lamiaceae Section Aethiopis), collected in two different
      biogeographical regions, has been analyzed. Samplel, collected in a Mediterranean
      like region, "As-Subayhi", contains mainly monoterpenes (54.2%), sesquiterpenes
      (27.6%) and phenylpropanoids (10.5%), while sample 2, collected in the Irano
      Turanian region, "Al-Adasiyyah", contains mainly phenylpropanoids (30.6%),
      monoterpenes (24.9%) and sesquiterpenes (21.2%). In Samplel, the most
      representative constituents were sabinene (21.5%), cis-chrysanthenyl acetate
      (20.8%), germacrene D (9.3%) and myristicin (5.9%), while in sample 2, myristicin
      (24.1%), sclareoloxide (6.3%), and germacrene D (5.7%) were main constituents.
      The rate of oxygenated derivatives in the Irano-Turanian sample was higher than
      the Mediterranean sample. Myristicin is an unusual constituent of Salvia species.

PMID- 24660485
TI  - GOP's health plan takes shape.

PMID- 24660486
TI  - Incubators boost IT startups.

PMID- 24660487
TI  - Getting to the root of the problem.

PMID- 24660489
TI  - Texas Medicaid tiptoes toward care coordination.

PMID- 24660488
TI  - Early bundled payment projects test positive.

PMID- 24660490
TI  - Congress' food stamp cuts undermine efforts to reduce healthcare costs.

PMID- 24660491
TI  - Physicians need to set stage for talk about long-term care.

PMID- 24660492
TI  - Hospital's simple interventions help reduce alarm fatigue.

PMID- 24660493
TI  - Cleveland clinic CEO talks strategy, expansion and standardization.

PMID- 24660494
TI  - Largest U.S. teaching hospitals.

PMID- 24660495
TI  - Inspections matter.

PMID- 24660496
TI  - Applying ergonomics to industrial glove design.

PMID- 24660497
TI  - Keys to preventing ladder falls.

PMID- 24660498
TI  - Update your fall protection program now: apply new ANSI Z359 equipment standards.

PMID- 24660499
TI  - Ending with a bang.

PMID- 24660500
TI  - Silica, spills, lawsuits, and rules.

PMID- 24660501
TI  - Safely aloft.

PMID- 24660503
TI  - Preparing for the worst.

PMID- 24660502
TI  - GHS: perception vs. reality.

PMID- 24660504
TI  - Cross-generation motivation & safety.

PMID- 24660505
TI  - From the president.

PMID- 24660506
TI  - Look where we are now!

PMID- 24660507
TI  - With a huff and a puff, your profession is blown away...building a solid
      foundation.

PMID- 24660508
TI  - What's the difference? OBN, ONA, ORC, OAC.

PMID- 24660509
TI  - No law is perfect: a case study of Obama Care.

PMID- 24660510
TI  - 2014 resolutions for a healthy, happy you!

PMID- 24660511
TI  - Oh my G...

PMID- 24660512
TI  - Improving service efficiency and effectiveness: the resource implications.

PMID- 24660513
TI  - Developing a Persian inpatient satisfaction questionnaire.
AB  - PURPOSE: Valid and reliable measures are required for assessing patient
      satisfaction meaningfully. The purpose of this paper was to develop and validate
      a Persian-language in-patient satisfaction questionnaire for patients discharged
      from Iranian medical and surgical services. DESIGN/METHODOLOGY/APPROACH: The
      cross-sectional survey included 400 patients randomly selected from six Tehran
      hospitals. A total of 405 patients responded to the questionnaire (76.3 percent
      response). To assess inter-item reliability and construct validity, factor
      analysis was carried out. Items belonging to each factor and their Cronbach's
      alpha coefficient were calculated. FINDINGS: A total of seven dimensions were
      identified: doctor-patient communication; nursing care; convenience; visitors;
      cleanliness; costs; and general satisfaction. Together, these dimensions
      explained 60 percent of the variance. All items, except three, revealed loadings
      above 0.4, while Cronbach's alpha exceeded 0.8 for all dimensions, except
      visitors (0.66). Patient satisfaction levels were relatively high. PRACTICAL
      IMPLICATIONS: Results must be interpreted cautiously owing to high satisfaction,
      which should not be considered as comprehensive evidence of high performance
      without important additional service-performance information. Qualitative studies
      are recommended to complement the authors' quantitative satisfaction study.
      ORIGINALITY/VALUE: The patient satisfaction questionnaire strives to be a valid
      and reliable instrument for assessing in-patient satisfaction with hospital
      services in Iran.

PMID- 24660514
TI  - Developing a hospital quality improvement initiative in Lesotho.
AB  - PURPOSE: Hospital-based quality improvement (QI) programs are becoming
      increasingly common in developing countries as a sustainable method of
      strengthening health systems. The aim of this paper is to present the results and
      lessons learned from a QI program in a large, rural, district hospital in
      Lesotho, Southern Africa. DESIGN/METHODOLOGY/APPROACH: Over a 15-month period, a
      locally-relevant, hospital-wide QI program was developed and implemented. The QI
      program consisted of: planning meetings with district and hospitals staff;
      creation of multi-disciplinary QI teams; establishment of a QI steering
      committee; design and implementation of a locally appropriate QI curriculum; and
      monthly consultation from technical advisers. Initial QI programming was
      developed in three distinct areas: maternity care, out-patient care, and referral
      systems. FINDINGS: Partogram documentation in the maternity department increased
      by 78 percent, waiting time for critically ill patients in the out-patient
      department was reduced by 84 percent, and emergency referral times were reduced
      by 58 percent. ORIGINALITY/VALUE: The design and early implementation of QI
      programs should focus on easily achievable, locally-relevant improvement
      projects. It was found that early successes helped to fuel further QI gains and
      the authors believe that the work building sustainable QI skill sets within
      hospital staff could be useful in the future when attempting to tackle larger
      national-level quality of care indicators. The findings add to the existing
      evidence suggesting that an increased use of locally-relevant quality improvement
      programming could help strengthen health care systems in low resource settings.

PMID- 24660515
TI  - Quality of coroner's post-mortems in a UK hospital.
AB  - PURPOSE: The aim of this paper was, principally, to look at the coroner's post
      mortem report quality regarding adult medical patients admitted to an English
      hospital; and to compare results with Royal College of Pathologists guidelines.
      DESIGN/METHODOLOGY/APPROACH: Hospital clinical notes of adult medical patients
      dying in 2011 and who were referred to the coroner's office to determine the
      cause of death were scrutinised. Their clinical care was also reviewed. FINDINGS:
      There needs to be a comprehensive approach to coroner's post-mortems such as
      routinely taking histological and microbiological specimens. Acute adult medical
      patient care needs to improve. RESEARCH LIMITATIONS/IMPLICATIONS: Steps should be
      taken to ensure that comprehensive coroner's post-mortems are performed
      throughout the UK, including with routine histological and microbiological
      specimens examination. Additionally, closer collaboration between clinicians and
      pathologists needs to occur to improve emergency adult medical patient clinical
      care. ORIGINALITY/VALUE: The study highlights inadequacies in coroner's pathology
      services.

PMID- 24660516
TI  - The new neck of femur fracture target: experience in a district general hospital.
AB  - PURPOSE: The hip fracture "best practice tariff" (BPT) came into effect in April
      2010. It advocated two key improvements: surgery within 36 hrs of arrival in the
      emergency department; and multi-disciplinary care directed by ortho-geriatrician
      from admission to discharge. The aim of this paper is to look at the 36 hours to
      operation target and its implications for orthopaedic department trauma service
      staff in a busy district general hospital, and to evaluate the measures
      implemented to meet the target. DESIGN/METHODOLOGY/APPROACH: Trauma-list data,
      collected from a theatre management system, was compared with trauma patients
      placed on elective and emergency lists, before and after designated daily trauma
      lists were implemented. FINDINGS: After a designated daily trauma list was
      introduced, a significant rise (from 56 per cent to 85 per cent) became evident
      in the proportion of patients operated on within 36 hrs, between November 2010 to
      February 2011, while hip fracture cases managed on the elective list fell from 24
      per cent to 17 per cent. PRACTICAL IMPLICATIONS: Despite adding a half-day trauma
      list, the trauma service has insufficient capacity to achieve the new BPT for all
      hip fracture patients in the hospital. Therefore, there is a significant knock-on
      effect for managing patient overspill on elective services. Will the significant
      changes in service provision designed to achieve this BPT be cost effective?
      ORIGINALITY/VALUE: This paper aims to answer how busy department staff address an
      issue that professionals in every English hospital are facing.

PMID- 24660517
TI  - Listening to patients: improving the outpatient service.
AB  - PURPOSE: This paper assesses the patients' healthcare information needs and
      expectations when they attend a rheumatology outpatient clinic. It proposes that
      obtaining the patients' perspectives about the services they use is an essential
      service-development tool. The aim of this paper is to expand the current domains
      used to evaluate these perspectives. DESIGN/METHODOLOGY/APPROACH: This paper is
      an exploratory study, looking at quality assessment and improvement based on
      Donabedian's quality model in a rheumatology outpatient setting. A structured
      interview schedule addressing care pathways was used and 70 consecutive patients
      were recruited. FINDINGS: The article provides insights about how relevant change
      can be brought about when service development is contemplated. It suggests that
      patients are important stakeholders in the ongoing service development process.
      RESEARCH LIMITATIONS/IMPLICATIONS: Because rheumatological conditions tend to be
      chronic and require long-term follow-up, the results may lack generalisability.
      Therefore, researchers are encouraged to test propositions in different clinical
      settings. PRACTICAL IMPLICATIONS: The article highlights healthcare delivery
      areas that are not meeting patient expectations. Some recommendations (such as
      informing waiting patients regularly about any delays) require minimal additional
      resources for successful implementation. Service providers need to obtain the
      patients' healthcare perspectives to ensure that services are built around their
      needs. ORIGINALITY/VALUE: This article fulfils an identified need to study how
      patients perceive service quality.

PMID- 24660518
TI  - ACE inhibitors and potassium foods--nurses' knowledge.
AB  - PURPOSE: According to Joint Commission standards, patients should be educated
      about drug-nutrient interactions. Because nurses are well-suited to educating
      patients, this paper aims to assess their knowledge of ACE inhibitor drugs,
      nutrient interactions and high- and low-potassium foods.
      DESIGN/METHODOLOGY/APPROACH: Licensed nurses from a teaching hospital in the US
      south eastern Atlantic region completed a self-administered questionnaire (n =
      83). Means, standard deviations and 95 percent confidence intervals were
      calculated for continuous data and frequency and percentage distribution for
      discrete data. Student's t-test was used to evaluate responses by ACE inhibitor
      patient load and nursing education. FINDINGS: Mean nurse knowledge of ACE
      inhibitors and potassium was 62 +/- 16 percent and identifying high- and low
      potassium foods was 32 +/- 23 percent. Most identified five from 12 high
      potassium foods and did not know the designation of six, one from 14 low
      potassium foods and did not know the designation of 11. Knowledge scores and
      identifying high- and low-potassium foods were similar regardless of ACE
      inhibitor patient load and nursing education. PRACTICAL IMPLICATIONS: ACE
      inhibitors are the fourth most commonly used drug class in the USA. Nurses are
      well positioned to recognize potential drug-nutrient interactions owing to
      changing or adding a drug, dose delivery method, dietary change or a patient's
      physical or clinical status that may indicate nutrient deficiency. The findings
      suggest that the nurses surveyed were proficient in identifying ACE inhibitors
      pharmacology, but that most were unable to identify foods that increase drug
      nutrient interaction risk, and thus this is an area in which additional training
      might be beneficial. ORIGINALITY/VALUE: Case menus were used to portray real-life
      scenarios in which healthcare practitioners can provide patient education about
      ACE inhibitor drug and dietary potassium interactions.

PMID- 24660519
TI  - Patient results and laboratory test accuracy.
AB  - PURPOSE: Traditional quality control materials used for monitoring the clinical
      laboratory test accuracy might be non-commutable with patient samples and may not
      detect systematic errors. The aim of this paper is to describe a method to
      monitor inter-instrument bias using result distributions that are independent of
      the control's commutability. DESIGN/METHODOLOGY/APPROACH: Serum calcium data
      collected within a laboratory network were assessed. A reference interval was
      calculated using a computerized, indirect Hoffmann's algorithm using all data
      across a laboratory network without excluding any results. Results outside the
      reference interval were considered as the zero-bias distribution. Three allowable
      bias levels were then calculated to determine the corresponding shift in abnormal
      results for each bias level in both directions from the zero-bias distribution.
      The observed result distributions in three laboratories within the network were
      compared for bias performance after one year of the reference interval study.
      FINDINGS: Performance levels for bias were: minimum allowable < 1.27 percent;
      desirable < 0.85 percent; and optimal < 0.42 percent. Zero bias result
      distribution above and below the reference interval for calcium was 3.92 percent
      and 2.53 percent respectively. All three laboratories performed within the
      desirable allowable bias level. ORIGINALITY/VALUE: Bias-monitoring process using
      patient result distributions allows managers to: assess systematic error between
      laboratory instruments; improve laboratory quality control; and strengthen
      patient risk management.

PMID- 24660520
TI  - Perspectives of significant others in dialysis modality decision-making: a
      qualitative study.
AB  - OBJECTIVE: To explore the experience of the dialysis modality decision-making
      process from the perspective of the significant other. METHODS: A qualitative
      interpretive description study was conducted using the Interprofessional Shared
      Decision Making Model (Legare et al., 2011). Data collection included one-on-one,
      semi-structured interviews, the Decisional Regret Scale, and the SURE tool.
      RESULTS: Ten significant others were interviewed. They included wives, husbands,
      and daughters of dialysis patients. Their roles involved providing a positive
      outlook, "being with", advocating, caregiving, learning together, sharing
      opinions, and communicating values, preferences and treatment feasibility.
      Broader factors influencing significant others included choosing life,
      unanticipated life change, and personal health problems. Implementation of the
      chosen modality resulted in unanticipated events, relationship changes and
      challenges to travelling. CONCLUSION: Significant others play supportive roles
      for dialysis patients and are involved in the decision-making process associated
      with treatment decisions. Significant others may have concurrent emotional,
      informational, and physical needs that affect their role in making and/or
      implementing the decision.

PMID- 24660522
TI  - The challenges presented by the non-compliant patient.

PMID- 24660521
TI  - An update on vancomycin dosing and monitoring practices in hemodialysis patients.

PMID- 24660523
TI  - Healthy skin.

PMID- 24660524
TI  - Parkinson's disease: a brain tune-up.

PMID- 24660525
TI  - Study reveals varying characteristics of assisted living residents.

PMID- 24660526
TI  - Rep. Renacci: a centrist with LTC experience.

PMID- 24660527
TI  - Demystifying QA record disclosure rules.

PMID- 24660528
TI  - Roles of Rho guanine nucleotide triphosphatases in hippocampal mossy fiber
      sprouting in the pentylenetetrazole kindling model.
AB  - BACKGROUND: One unique feature of chronic human and experimental epilepsy is
      hippocampal dentate granule cell axon (mossy fiber) sprouting which creates an
      aberrant positive-feedback circuit that may be epileptogenic. However, the
      mechanism underlying this process remains unclear. Rho guanine nucleotide
      triphosphatases (RhoGTP ases) Rac1 and RhoA are important regulators of axon
      growth and synaptic plasticity and can be blocked by treatment with fasudil. We
      hypothesized that Rac1 and RhoA are involved in aberrant mossy fiber sprouting
      (MFS). METHODS: A temporal lobe epilepsy model was established by intraperitoneal
      pentylenetetrazole (PTZ) injection for animals in PTZ group, and fasudil was
      injected 30 minutes prior to PTZ injection for animals in PTZ + Fas group. The
      expression of Rac1 and RhoA in the rat hippocampus was tested at different time
      points by immunohistochemistry, Western blot and quantitative real-time PCR.
      Mossy fiber sprouting in the hippocampus was evaluated by Timm staining. RESULTS:
      Rac1 and RhoA were significantly up-regulated in the PTZ group, and as predicted,
      the degree of aberrant MFS was correspondingly increased. However, the expression
      of Rac1 and RhoA was not inhibited in the PTZ + Fas group, and the epileptiform
      activity, EEG and aberrant MFS were not suppressed following PTZ + Fas treatment.
      CONCLUSIONS: RhoGTPases play a role in MFS but fasudil is not sufficient to
      inhibit RhoGTPases and MFS in the PTZ kindling model.

PMID- 24660529
TI  - Current information concerning association of IL-12 and hepatitis B infection.
AB  - BACKGROUND: Hepatitis B is one of the most prevalent infectious diseases and is
      induced by hepatitis B virus (HBV). The chronic, asymptomatic, and occult forms
      of hepatitis B are long-term infections that can lead to various hepatic cancers
      and cirrhosis in the carrier. IL-12 is one of the main cytokines involved in
      inducing appropriate immune responses against viral infections, especially HBV.
      Therefore, the aim of the present review was to address the most recent
      information within the database regarding the status and association between IL
      12 and hepatitis B infection and its complications including cirrhosis and
      hepatocellular carcinoma. METHODS: The data presented was collected by searching
      the following keywords in the Pubmed and Scopous databases: Hepatitis B, occult
      HBV infection, chronic HBV infection, asymptomathic HBV infection, acute HBV
      infection, fulminant HBV infection, IL-12, and all the papers regarding the
      relation between IL-12 and hepatitis B were used. These data were presented in
      the current review article. RESULTS: Results showed that IL-12 plays important
      roles in Hepatitis B infection and patients infected with the long-term form of
      hepatitis B are unable to produce sufficient amount of this cytokine.
      CONCLUSIONS: Our research provided mechanistic insights into the immunoprotective
      roles of IL-12 and proposed that it can be considered as an important molecule
      for immunotherapy of HBV infected infection.

PMID- 24660530
TI  - Establishment and validation of serum free light chain reference intervals in an
      ethnic Chinese population.
AB  - BACKGROUND: Quantification of serum free light chains (FLC) and calculation of a
      kappa/lambda ratio using polyclonal antisera based immunoassays provide
      laboratories with a sensitive alternative to urine protein electrophoresis (UPE).
      However, the published 0.26 - 1.65 serum FLC kappa/lambda ratio reference
      intervals may not be suitable for different ethnic populations (such as the Han
      Chinese population presented) and require validation. This is particularly
      important where there are significant differences in ethnicity, and hence HLA
      prevalence, in the population studied. METHODS: Serum FLC reference intervals
      were determined using 326 Han Chinese blood donor volunteers. Sensitivities and
      specificities for the (i) serum FLC kappa/lambda ratio reference interval and
      (ii) UPE analyses were determined using 68 pre-treatment, serum immunofixation
      (sIFE) positive multiple myeloma (MM) patient samples, 54 sera from MM patients
      undergoing treatment, and 56 sIFE-negative samples from patients with no plasma
      cell dyscrasia (PCD). RESULTS: The 100% range for the serum FLC kappa/lambda
      ratio in this Han Chinese population was 0.32 - 1.52. Both Han Chinese blood
      donors and published kappa/lambda ratio reference ranges demonstrated higher
      diagnostic sensitivity and specificity for PCD than was seen with UPE. Highly
      abnormal serum FLC kappa/lambda ratios were observed in 68% of MM patients who
      had a negative UPE. Furthermore, a MM screening panel of SPE plus serum FLC
      assays achieved 100% diagnostic sensitivity compared to 97% for a UPE plus SPE
      algorithm. For MM patients undergoing therapy, 70% of UPE negative samples
      displayed an abnormal FLC ratio. CONCLUSIONS: This study confirms the requirement
      to verify normal FLC reference ranges in local populations. This Han Chinese
      reference range is narrower than the published range. FLC testing provides a
      robust, sensitive, and specific alternative to classic UPE assessment.

PMID- 24660531
TI  - Association of red cell distribution width with the presence of coronary artery
      ectasia.
AB  - BACKGROUND: Red cell distribution width (RDW) has recently been considered as a
      strong predictor of a variety of acute and chronic cardiovascular diseases, while
      the association between RDW and coronary artery ectasia (CAE) has not been
      elucidated yet. The aim of the present study was to evaluate the association of
      RDW levels in the presence of the CAE. METHODS: One hundred and sixty-four
      consecutive patients including 84 patients (69 male, mean age: 55 +/- 11 years)
      with isolated CAE and 60 angiographically normal controls (48 male, mean age: 52
      +/- 13 years) were enrolled. Blood samples were drawn to measure RDW and C
      reactive protein (CRP). Baseline clinical characteristics and laboratory findings
      were compared between the two groups. RESULTS: The levels of RDW were
      significantly higher in patients with isolated CAE than that in normal controls
      (12.94 +/- 2.1 vs. 12.48 +/- 1.4, p = 0.021). In addition, the levels of CRP were
      also higher in patients with CAE compared with normal controls (0.28 +/- 0.14
      mg/L vs. 0.21 +/- 0.11 mg/L, p = 0.047). The multivariate analysis indicated that
      RDW and CRP were the independent variables most strongly associated with the
      presence of isolated CAE. Finally, correlation analysis suggested that there was
      positive correlation between plasma levels of CRP and RDW levels in patients with
      CAE (n = 84, gamma = 0.358, p = 0.001). CONCLUSIONS: The data demonstrated that
      RDW levels were significantly higher in patients with isolated CAE, suggesting
      that RDW may be a valuable marker for the patients with CAE.

PMID- 24660532
TI  - Prooxidant-antioxidant balance and hs-CRP in patients with beta-thalassemia
      major.
AB  - BACKGROUND: Beta-thalassemia major is one of the most frequent hemoglobinopathies
      in the world. This is a study on the levels of prooxidant-antioxidant balance
      (PAB) that can measure the pro-oxidant burden and the anti-oxidant capacity
      simultaneously in one assay, giving a redox index, as well as an assessment of
      high-sensitivity C-reactive protein (hs-CRP) in patients with beta-thalassemia
      major. It also determines the impact both on kidney function tests. METHODS:
      Ninety subjects with beta-thalassemia major (betaTM) and 90 more healthy subjects
      as the control group were enrolled in the study. Laboratory parameters, serum hs
      CRP, and the novel assay of prooxidant-antioxidant balance were measured.
      RESULTS: Biochemical and hematological variables, except MCHC, were significantly
      decreased in patients. Ferritin (p < 0.001) and PAB (p < 0.001) values were
      statistically increased in patients, whereas hs-CRP (p > 0.05) did not
      significantly increase in patients. Spearman's correlation univariate analysis
      showed no significant correlation between PAB with hs-CRP or ferritin. However,
      there was a significant statistical correlation between hs-CRP with creatinine
      and triglycerides. Also we found a slight and negative correlation between high
      density lipoprotein cholesterol, hemoglobin, and hemotocrit with inflammatory
      factor. CONCLUSIONS: Briefly, we found higher levels of PAB values and a slight
      increase in hs-CRP concentration in patients, which may be involved in the
      pathological consequences of beta-thalassemia major and contribute to the gradual
      development of injury to the organs.

PMID- 24660533
TI  - Evaluation and comparison of different approaches for the detection of PNH clones
      by flow cytometry following the ICCS guidelines.
AB  - BACKGROUND: Comparison between consensual approaches for the detection of
      paroxysmal nocturnal hemoglobinuria (PNH) clones by flow cytometry (FCM)
      following the international clinical cytometry society (ICCS) guidelines has not
      been widely reported. METHODS: We determined the performance characteristics of
      4, 5, and 6-color protocols for white blood cell (WBC) and one and two-color
      protocols for red blood cell (RBC) evaluation for different PNH target clones and
      compared results from PNH patient analysis. RESULTS: Coefficient of variation
      (CV) for precision/reproducibility analysis ranged from 0.01%/0.12% to 2.56%/
      3.59% for granulocytes, from 0.07%/0.08% to 3.87%/11.61% for monocytes and from
      0.4%/1.02% to 6.53%/ 5.1% for RBCs within different approaches and target PNH
      clones. Comparison of individual protocols revealed excellent correlation (r =
      0.99), Wilcoxon rank tests found no statistically significant differences (p >
      0.05), Bland-Altman analysis proved agreement for all PNH clones (mean bias
      ranging from 0.02 to 2.2). CONCLUSIONS: Our results confirm good intralaboratory
      characteristics for precision and reproducibility analysis, excellent correlation
      and agreement between approaches underlining the primary role of optimally
      selected glycophosphatidylinositol (GPI)-specific reagents and secondary role of
      number, type of gating reagents and gating strategy.

PMID- 24660534
TI  - An observational study of Venlafaxine and CYP2D6 in clinical practice.
AB  - BACKGROUND: Venlafaxine (V) is a serotonin-norepinephrine selective reuptake
      inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6
      polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs),
      extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor
      tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim
      of this study was to evaluate the impact of CYP2D6 genotype on V dosage,
      therapeutic response, and side effects in a clinical outpatient setting. METHODS:
      47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day,
      underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of
      treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness
      index) were assessed. RESULTS: CGI assessment was performed after 6 weeks, 6
      months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6
      genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V
      dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 -
      300 mg) without adverse effects; EMs displayed high response variability.
      CONCLUSIONS: PM/IM patients responded to V differently than expected according to
      genotype. However, the UM patient responded to a dosage higher than the usual
      therapeutic range and without developing side effects, suggesting an association
      between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The
      CYP2D6 genotyping may thus provide clinicians with a potential explanation for
      those patients requiring greater doses of CYP2D6 substrates in order to obtain
      the same therapeutic efficacy.

PMID- 24660535
TI  - Expression of SOCSs and TLRs in the hippocampus of pentylenetetrazole kindling
      model.
AB  - BACKGROUND: Epilepsy is one of the most common neurological disorders, and
      approximately one-third of patients with epilepsy are resistant to anti-epileptic
      drugs (AEDs). Recent emerging evidence has demonstrated the roles of innate
      immunity and the associated inflammatory processes in epilepsy. Toll-like
      receptors (TLRs) are a type of pattern-recognition receptor that promote innate
      immune defense. The SOCS proteins as negative-feedback regulators in cytokine
      signaling are involved in the regulation of TLR-mediated immune responses.
      However, few studies investigating the role of TLRs and SOCSs in epilepsy have
      been reported. METHODS: To explore the role of innate immunity in the mechanism
      of epilepsy, the pentylenetetrazole (PTZ) kindling rat model was established
      using intraperitoneal injection of PTZ. The expression levels of TLR2, TLR4, and
      STAT molecules in rat hippocampi were analyzed using qRT-PCR and western blotting
      techniques. The expression levels of SOCS-1 and SOCS-3 in rat hippocampi were
      analyzed using qRT-PCR. RESULTS: Our data demonstrated that both the mRNA and
      protein expression of TLR2 and TLR4 were significantly upregulated in the rat
      hippocampus with PTZ injection, which was accompanied by an inhibition of SOCS-1
      and SOCS-3 and an upregulation of STAT3. CONCLUSIONS: Our study suggested that
      SOCSs and TLRs contribute to the development of epilepsy which may lead to
      therapeutic interventions that limit epileptogenesis.

PMID- 24660536
TI  - Evaluation of an automated microplate technique in the Galileo system for ABO and
      Rh(D) blood grouping.
AB  - BACKGROUND: A number of automated devices for pretransfusion testing have
      recently become available. This study evaluated the Immucor Galileo System, a
      fully automated device based on the microplate hemagglutination technique for
      ABO/Rh (D) determinations. METHODS: Routine ABO/Rh typing tests were performed on
      13,045 samples using the Immucor automated instruments. Manual tube method was
      used to resolve ABO forward and reverse grouping discrepancies. D-negative test
      results were investigated and confirmed manually by the indirect antiglobulin
      test (IAT). RESULTS: The system rejected 70 tests for sample inadequacy. 87
      samples were read as "No-type-determined" due to forward and reverse grouping
      discrepancies. 25 tests gave these results because of sample hemolysis. After
      further tests, we found 34 tests were caused by weakened RBC antibodies, 5 tests
      were attributable to weak A and/or B antigens, 4 tests were due to mixed-field
      reactions, and 8 tests had high titer cold agglutinin with blood qualifications
      which react only at temperatures below 34 degrees C. In the remaining 11 cases,
      irregular RBC antibodies were identified in 9 samples (seven anti-M and two anti
      P) and two subgroups were identified in 2 samples (one A1 and one A2) by a
      reference laboratory. As for D typing, 2 weak D+ samples missed by automated
      systems gave negative results, but weak-positive reactions were observed in the
      IAT. CONCLUSIONS: The Immucor Galileo System is reliable and suited for ABO and D
      blood groups, some reasons may cause a discrepancy in ABO/D typing using a fully
      automated system. It is suggested that standardization of sample collection may
      improve the performance of the fully automated system.

PMID- 24660537
TI  - Transplantation of cryopreserved human ovarian tissue: restoration of
      reproductive function after two cycles of radio- and chemo-therapeutic
      treatments.
AB  - BACKGROUND: Patient S. was born in 1983, developed a Ewing-Sarcoma and obtained
      low dose chemotherapy in 1996. In 2007, Patient S. received high-dose
      chemotherapy because lung-metastases were diagnosed. The aim of the study was to
      investigate the health of cryopreserved ovarian tissue and also to examine
      whether this ovarian tissue can restore the reproductive function of patient
      after two cycles of radio-and chemo-therapeutic treatments. METHODS: Twenty
      pieces of ovarian tissue (total of approximately 200 mm2) were conventionally
      frozen with 6% (v/v) dimethyl sulfoxide, 6% (v/v) ethylene glycol and 0.15 M
      sucrose and kept for five years before 8 pieces were thawed and transplanted back
      into the patient. Two small (1 x 2 x 1 mm) pieces of this thawed tissue were
      cultured in a chicken embryonic chorioallantoic membrane (CAM)-system for 5 days
      to assess the tissue viability. RESULTS: The ovarian tissue that was grafted re
      established spontaneous menstrual bleeding within five months and serum 17-beta
      estradiol increased from 19 to 330 pg/mL. Ultrasound revealed a dominant follicle
      at the site of the transplanted tissue in the follicular phase after the
      menstrual bleed. Analysis of the CAM cultured tissue established that 88% of the
      primordial follicles had degenerated and there was limited growth of blood
      vessels. CONCLUSIONS: In spite of the damage caused by the cryopreservation the
      surviving follicles could restore ovarian function after re-transplantation.

PMID- 24660538
TI  - The activity of 8-iso-prostaglandin F2alpha as an oxidative stress marker in vivo
      in paediatric patients with type 1 diabetes mellitus and associated
      autoimmunities.
AB  - BACKGROUND: Oxidative stress and inflammatory reactions are known to hold an
      important role in the etiopathogeny and persistence of acute or chronic clinical
      entities. Isoprostanes--a group of prostaglandin-like compounds, active products
      of arachidonic acid--have proved to be representative biomarkers of lipid
      peroxidation. The aim of this study was to determine the activity of serum 8-iso
      prostaglandin F2alpha, (8iPGF2alpha), as an in vivo oxidative stress marker, in
      paediatric patients with diabetes mellitus type 1 (DM1) and in a control group.
      The main goals of this study were the following: establishing a possible
      correlation between the activity of 8iPGF2alpha and the presence of an autoimmune
      disease associated with DM1 and identifying a possible correlation between
      8iPGF2alpha, the value of glycosylated hemoglobin (HbA1c) and the pancreatic
      autoimmune markers GAD65, IA2, IA in the group of patients with DM1 and other
      associated autoimmune diseases. METHODS: Fifty-one children and adolescents (31
      males) aged 11.65 +/- 4.1 years with DM1 were enrolled in the study. Twenty-seven
      healthy children, age- and gender-matched, were enrolled as controls. Patients
      and controls underwent the 8iPGFzalpha assessment through an ELISA serum method.
      RESULTS: The mean 8iPGF2alpha value was 2090.6 +/- 3536.5 in the DM1 patient
      group and 509.9 +/- 493.5 in controls (p = 0.03). The mean 8iPGF2alpha value was
      2178.19 +/- 4017.05 in patients with DM1 who did not suffer from other associated
      autoimmune diseases (n = 38) vs. 1834.95 +/- 1504.73 in patients with DM1 and
      other associated autoimmune diseases (n = 13) (p = 0.76). The correlation between
      the 8iPGF2alpha and the HbA1c values was determined by obtaining a correlation
      coefficient r = 0.38 and p = 0.0057. No correlation was observed between GAD65
      and 8iPGF2alpha (r = 0.3; p = 0.29), IA2 and 8iPGF2alpha (r = -0.02; p = 0.92),
      IAA and 8iPGF2alpha (r = 0.4; p = 0.12). CONCLUSIONS: Oxidative stress reactions
      are more intense in patients with diabetes mellitus type 1 than in healthy
      patients. Similar results were obtained in patients associating other autoimmune
      diseases. 8iPGF2alpha can be an ideal marker for determining oxidative reactions
      in vivo.

PMID- 24660539
TI  - Decreased activated protein C levels are inversely associated with the urinary
      albumin excretion rate in patients with type 2 diabetes.
AB  - BACKGROUND: Activated protein C (APC) plays a vital renoprotective role against
      diabetic nephropathy in STZ-induced diabetic mice by inhibiting endothelial cell
      and podocyte apoptosis. This study aimed to examine the relationship between the
      degree of albuminuria and APC levels in patients with type 2 diabetes. METHODS:
      Ninety-four patients with type 2 diabetes and 38 healthy subjects were recruited
      into this study. The urinary albumin concentrations of urine collected over 24
      hours were measured by ELISA to evaluate the mean urinary albumin excretion rate
      (UAER). The HbA1c levels were determined using an HPLC assay. RESULTS: There was
      no significant difference in the APC levels between diabetic patients with
      normoalbuminuria and controls, although APC levels were significantly lower in
      diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 54.58 +/- 53.63
      pg/mL, p < 0.05) or macroalbuminuria (8.06 +/- 10.09 vs. 54.58 +/- 53.63 pg/mL, p
      < 0.05) as compared to control subjects. In addition, in comparison to diabetic
      patients with normoalbuminuria, APC levels were lower in diabetic patients with
      microalbuminuria (23.06 +/- 19.82 vs. 55.69 +/- 31.98 pg/mL, p < 0.05) and they
      were the lowest in diabetic patients with macroalbuminuria (8.06 +/- 10.09 vs.
      55.69 +/- 31.98 pg/mL, p < 0.05). Multivariate regression and ROC analysis found
      that the levels of APC and HbA1c were independent risk factors for UAER levels
      (R2(ad) = 0.61, f = 25.69, p < 0.01) and the value of APC < or = 41.588 pg/mL
      indicated elevated albuminuria in patients with type 2 diabetes. CONCLUSIONS:
      Decreased APC levels in patients with type 2 diabetes may serve as a biomarker to
      indicate the early development of diabetic nephropathy.

PMID- 24660540
TI  - Human papillomavirus (HPV) prevalence and types among women attending regular
      gynecological visit in Tehran, Iran.
AB  - BACKGROUND: Persistent infection by HPV is now recognized as the main cause of
      cervical cancer. HPV prevalence data is not yet available in Iran. This study is
      organized to evaluate type-specific HPV prevalence and to compare it with Pap
      smear results among Iranian women attending regular gynecological visits.
      METHODS: A total of 851 women aged 18 - 65 years, attending regular gynecological
      visits, were retrospectively evaluated. HPV detection and genotyping was
      performed by use of Polymerase Chain Reaction (PCR) and Restriction Fragment
      Length Polymorphism (RFLP). Cytological evaluation was done by Papanicolaou
      method and the association between cytological results and HPV status was
      analyzed. RESULTS: 19 different HPV types were detected in 265 of the 851
      specimens (31.1%). Overall HPV infection as well as infection with High Risk (HR)
      HPV types was highest in women aged 18 - 25 years and decreased with age. Type
      specific prevalence of HPV-16 and 18 was 7.3% and 2.8%, respectively, and a large
      number of women (20.2%) were infected by HR HPV types other than HPV-16 and/or
      HPV-18. There was also an upward trend in the prevalence of HR HPV infections as
      the abnormality in cytology increased. The prevalence of HPV co-infection was
      29.1% of HPV positive patients and declined from LSIL (18.2%) to HSIL (3.9%).
      CONCLUSIONS: Our study indicated that the burden of HPV infection among Iranian
      females was higher in comparison with previous estimates reported from Iran.
      Furthermore, higher prevalence of premalignant changes in Iranian women infected
      with HR HPV types, other than vaccine types, should be considered in immunization
      programs and development of population-specific HPV vaccines. This remarkable
      difference in prevalence of HPV types among previous studies, confirms our need
      to further investigations on epidemiology of HPV infection in Iran.

PMID- 24660541
TI  - Evaluation of the automated urine particle analyzer UF-1000i screening for
      urinary tract infection in nonpregnant women.
AB  - BACKGROUND: Urinary tract infection (UTI) is a widespread disease in women. Urine
      culture is still the "gold standard" diagnostic test for UTI, but most of them
      are negative. To reduce unnecessary culture, we evaluated the automated urine
      particle analyzer UF-1000i screening for UTI in nonpregnant women. METHODS: The
      urine specimens submitted to our laboratory were submitted for culture and tested
      by the Sysmex UF-1000i. Bacteria and white blood cell (WBC) counts were compared
      to standard urine culture results to assess the best cutoff values. RESULTS: In
      this study, 272 urine samples were included, of which 98 (36.0%) were culture
      positive with a bacterial cutoff value of 10 x 10(5) CFU/mL. A combination of
      bacterial (> 95/microL) and/or WBC count (> 24/microL) provided the best
      screening for UTI, with a sensitivity of 0.99 and a specificity of 0.82 compared
      with the urine culture. CONCLUSIONS: Sysmex UF-1000i could be used as a screening
      test for UTI in nonpregnant women. According to the distribution and range of the
      bacterial scattergram, we could primarily identify and differentiate between Gram
      negative and Gram-positive bacteria.

PMID- 24660542
TI  - Cardiac troponin I in patients with chronic kidney disease stage 3 to 5 in
      conditions other than acute coronary syndrome.
AB  - BACKGROUND: Elevations of cardiac troponin I (cTnI) not associated with acute
      coronary syndrome (ACS) have been reported in patients with chronic kidney
      disease (CKD) stage 5 or end-stage renal disease (ESRD). The aim of this study
      was to determine the prevalence of elevated cTnI in patients with CKD stage 3 to
      5 in conditions other than ACS. METHODS: The study population consisted of 426
      patients with CKD stage 3 to 5 (estimated glomerular filtration rate < 60
      mL/minute/1.73m2 calculated with the MDRD-4 equation) admitted with symptoms of
      ACS but finally this diagnosis was ruled out with determinations of cTnI and
      medical history, physical examination, and electrocardiography. Levels of cTnI in
      serum were measured at admission, at 6 - 12 hours and at 6 months with two
      different analytical methods (Access and Vidas analyzers). Patients were assigned
      into the following two groups according to the clinical diagnosis: 1) patients
      with Other Cardiac Diseases (OCD) and 2) patients with Other Noncardiac Diseases
      (ONCD). RESULTS: The OCD group included 140 patients (33%) and the ONCD group
      included 286 patients (67%). We found elevated cTnI (higher than 99th percentile)
      with the Access and Vidas analyzers in 32% of patients. The prevalence of
      elevated cTnI was higher in patients with CKD stage 5 or ESRD. In the OCD group,
      the most common diagnoses were congestive heart failure (52.1%) and atrial
      fibrillation (20%), whereas in the ONCD group they were arterial hypertension
      (8.4%) and cerebrovascular accident (8.1%). The rate of mortality in patients
      with CKD stage 3 to 5 was 17% but was higher in patients with CKD stage 5 (40%).
      CONCLUSIONS: Elevations of cTnI not associated with ACS were common in patients
      with CKD stage 3 to 5, and there was an increase in mortality with higher
      concentrations of cTnI.

PMID- 24660543
TI  - Research on the roles of transcription factors T-bet and GATA-3 in aplastic
      anemia.
AB  - BACKGROUND: Aplastic anemia (AA) is a type of bone marrow hematopoietic system
      disease. The immune mediated hematopoietic inhibition is recognized as the most
      common pathogenesis of AA. However, the roles of the T-bet/GATA-3-mediated cell
      immune disorder in aplastic anemia (AA) is still unknown. METHODS: Experimental
      samples were obtained from 27 patients with AA, including 15 cases of severe AA
      (SAA) and 12 cases of immune mediated AA (MAA), and 25 healthy volunteers
      (control group). The secretory levels of IFN-gamma and IL-4 cytokines were
      determined by ELISA. The mRNA expression levels of transcription factors T-bet,
      GATA-3, and FoxP3 were measured in PBMCs by RT-PCR. Th1, Th2, and T lymphocyte
      subsets were detected in peripheral blood by flow cytometry. RESULTS: Compared to
      the healthy control group, the expression of T-bet mRNA and the percentage of Th1
      type cells in the AA group significantly increased (p < 0.01), while the
      expression of GATA-3 and FoxP3 mRNA and the percentage of Th2-type cells
      decreased sharply (p < 0.05, p < 0.01). Compared with MAA, the expression of T
      bet mRNA and the percentage of Th1-type cells increased significantly in SAA (p <
      0.01); meanwhile, the expression of GATA-3 mRNA and the proportion of Th2-type
      cells decreased noticeably (p < 0.05, p < 0.01). Particularly, the percentage of
      CD3+ and CD3+CD8+ T cells in the AA group increased (p < 0.05), while the
      percentage of CD3+CD4+, CD4+CD25+, and CD4+CD8+ cells decreased (p < 0.05, p <
      0.01). CONCLUSIONS: Abnormal expression of the transcription factors T-bet and
      GATA-3 contributes to the imbalance of Thl/Th2 lymphocytes associated with immune
      dysfunction, leading to the development and progression of AA.

PMID- 24660544
TI  - Evaluation of the FluA-Ag rapid assay for detection of influenza A viruses of
      human, avian, and swine origin.
AB  - BACKGROUND: Influenza viruses which cause human disease may include viruses that
      originate from humans, animals, or animal/human reassortants. This study
      evaluated the diagnostic sensitivity and specificity of a commercial FluA-Ag
      rapid assay in detecting influenza A viruses, either common or reassortant
      strains, to meet the need of influenza A virus early screening. METHODS: The
      laboratory accuracy of the rapid assay was evaluated using influenza A virus
      isolated strains and other related respiratory virus strains. The diagnostic
      sensitivity and specificity were assessed using clinical specimens from
      hospitals, poultry and pig farms. Nucleic acid testing (real-time RT-PCR) was
      used as the reference method, and all samples with different results detected by
      the rapid assay and real-time RT-PCR were confirmed by sequencing for full
      identification. RESULTS: Compared with the detection results of real-time RT-PCR,
      the rapid assay showed high laboratory accuracy with influenza A virus strains
      and other respiratory virus strains, and it also showed a higher relative
      diagnostic sensitivity and specificity of the rapid assay with clinical samples.
      CONCLUSIONS: The high accuracy and the higher diagnostic sensitivity and
      specificity for influenza A virus detection proved that this rapid assay will be
      a valuable tool for the quick detection of influenza A virus in the laboratory or
      on-site locations.

PMID- 24660545
TI  - Internal quality control practice of thyroid disease related tests and
      imprecision analysis in China.
AB  - BACKGROUND: Internal quality control (IQC) has a long and well-established role
      in clinical laboratories and the quality of laboratories has achieved great
      improvement in China. However, the practice of IQC varies significantly between
      institutions and many problems still exists. Consequently, the Chinese National
      Center for Clinical Laboratories has been undertaking monthly nation-wide surveys
      of current IQC practice of tests since 2010 to monitor laboratory quality.
      Thyroid disease related tests were chosen for this research. METHODS: Different
      numbers of laboratories in China participating national external quality
      assessment (EQA) schemes of Total Thyroxine (TT4), Total Triiodothyronine (TT3),
      Free Thyroxine (FT4) and Free Triiodothyronine (FT3) tests, and Thyroid
      Stimulating Hormone (TSH) measurements, were required to report the IQC
      information though the national external quality assessment (EQA) network
      platform. RESULTS: Survey data showed significant variability in all aspects of
      IQC practice. More than half of the laboratories are using a single concentration
      level of IQC material and up to 28.6% of the laboratories only use 1(2s) or 1(3s)
      to monitor IQC results for FT3, TT3, FT4, TT4, and TSH. The medians of the
      average time intervals of two control tests for FT3, TT3, FT4, TT4, and TSH are
      33.6, 35.4, 33.6, 35.4, and 33.6 hours, respectively, more or less 1.4 days. When
      quality specifications based on biological variation are applied to imprecision
      evaluation, only 46.3%, 52.1%, 31.3%, 12.8%, and 5.86% laboratories meet the
      minimum performance for FT3, TT3, FT4, and TT4, 24.5%, 23.6%, 12.8%, and 5.86% of
      the all meet the desirable performance, and 4.4%, 3.9%, 2.5% and 3.0% of the all
      meet the optimal performance. While it shows a higher percentage of acceptable
      laboratories (98.1%, 87.9% and 39.0% meeting the minimum, desirable and optimal
      performance, respectively) for TSH. CONCLUSIONS: Not-well-designed IQC practices
      may affect the effectiveness of laboratory IQC and, thus, the adequacy of a
      laboratory to monitor system performance. Consequently, IQC practice should be
      designed according to performance of measure method and instrument. Both clinical
      laboratories and the government should make efforts to improve quality of
      clinical testing to ensure the patients' safety.

PMID- 24660546
TI  - Association between uric acid and severity of pre-eclampsia.
AB  - BACKGROUND: The objective of this study was to evaluate the use of uric acid as a
      marker of severity of pre-eclampsia. METHODS: Uric acid was measured in 36 pre
      eclamptic pregnant women and 26 healthy pregnant women in the control group. Data
      regarding age, history of pre-eclampsia in previous pregnancies, family history
      of pre-eclampsia, pregnancy, and abortion were obtained through a questionnaire
      given to each pregnant woman, after signing the consent form. The route of
      delivery and weight of the newborns were obtained from medical records of
      patients. Statistical analyses used were the t-test and Fisher's exact test.
      RESULTS: Uric acid was significantly higher and weight of neonates was
      significantly lower in pre-eclamptic women. Significant correlations between uric
      acid and systolic blood pressure, and uric acid and 24-hour proteinuria were
      observed. Inverse correlations between uric acid levels and weight of newborns
      and between systolic blood pressure and the weight of newborns were also
      observed. CONCLUSIONS: The results agree with other previous research, and
      reinforce the idea that the concentration of serum uric acid in pregnant women
      with pre-eclampsia is associated with disease severity and contributes to better
      monitoring of the mother and newborn.

PMID- 24660547
TI  - A syndrome of insulin resistance resembling Donohue syndrome with patent ductus
      arteriosus.
AB  - Donohue syndrome, a rare autosomal recessive disorder, is associated with the
      mutation of the insulin receptor gene in the short arm of the 19th chromosome. It
      is very rare that a syndrome of insulin resistance resembles Donohue syndrome
      with patent ductus arteriosus. A 14-year-old girl, whose parents were
      consanguineous, was often admitted for abdominal pain over the past 8 years. She
      presented not only polydipsia, polyphagia, and weight loss but also small elfin
      face, distended abdomen, enlarged clitoris, hypertrichosis, acanthosis nigricans
      of the neck, decreased subcutaneous fat and 3/6 continuous murmur radiating to
      the right shoulder with thrill on 2nd to 3rd left sternal border. In addition,
      she had hyperglycemia, hyperinsulinism, and patent ductus arteriosus by
      laboratory examination and echocardiography, respectively. This child shows
      insulin resistance resembling Donohue syndrome with patent ductus arteriosus.
      Most of patients with Donohue syndrome die prematurely. The child surviving for a
      long time may have a milder form of Donohue syndrome and may be due to a less
      severe form of the defective gene. Chromosomal abnormalities may be also
      associated with this disease.

PMID- 24660548
TI  - High-density lipoprotein size distribution can differ between subjects with
      alcoholic and non-alcoholic fatty liver disease.
AB  - BACKGROUND: While alcohol consumption is associated with levels of high-density
      lipoprotein (HDL)-cholesterol (HDL-C), a cardiovascular risk marker, HDL size
      distribution has yet to be characterized in subjects with alcoholic fatty liver
      disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). METHODS: The
      present study compared HDL subfractional characteristics between subjects with
      AFLD (36 men, age 61 +/- 14) and NAFLD (35 men, age 65 +/- 13), recruited during
      general health check-ups. Serum HDL subfractions were measured with the
      electrophoretic separation of lipoproteins employing the Lipoprint system.
      RESULTS: The subjects with AFLD had a significantly greater proportion of small
      sized HDL part (6.6 +/- 5.7%) than those with NAFLD (3.8 +/- 4.9%, p = 0.029).
      CONCLUSIONS: More percentages of small-sized HDL part were observed in the
      subjects with AFLD than in those with NAFLD in Japanese general population.
      Whether the difference of HDL size is associated with cardiovascular
      manifestations should be studied further.

PMID- 24660549
TI  - Transient hypoxia leads to increased serum levels of heat shock protein-27, -70
      and caspase-cleaved cytokeratin 18.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a worldwide burden.
      We have previously shown that elevated levels of heat shock protein-27 (HSP27), 
      70 (HSP70), and caspase-cleaved cytokeratin 18 (ccCK-18) were found in serum of
      COPD patients correlating with disease severity. We hypothesized that transient
      hypoxia triggers the release of HSPs and ccCK-18. METHODS: Fourteen healthy
      volunteers were subjected to transient normobaric hypoxia in an air-conditioned
      hypoxia chamber simulating an oxygen concentration at an altitude of up to 5500
      meters. Serum samples were evaluated for HSP27, -70, and ccCK-18. RESULTS:
      Baseline concentrations were 2760 pg/mL +/- 517 SEM for HSP-27, 49 pg/mL +/- 22
      SEM for HSP-70, and 226 U/L +/- 20 SEM for ccCK-18. After eight hours and an
      altitude equivalent of 5500 meters a significant increase was recorded, depicted
      by serum levels of 3737 pg/mL +/- 571 SEM for HSP-27, 202 pg/mL +/- 81 SEM for
      HSP-70, and 244 U/L +/- 20 SEM for ccCK-18 (p < 0.05). CONCLUSIONS: These results
      provide an explanation for the elevated serum levels of HSP-27, HSP-70, and ccCK
      18 found in COPD patients, indicating that hypoxic conditions can trigger the
      release of the aforementioned factors.

PMID- 24660550
TI  - Quality assurance of gelcards centrifuged multiple times before use for testing.
AB  - BACKGROUND: Further use of reagents, that have not been consumed in total by
      tests in the laboratory, is of financial and ecological interest. If there are no
      instructions by the manufacturer, such a procedure must be validated thoroughly.
      As gelcards of the DiaMed-ID Micro Typing System contain 6 microtubes for
      immunohematological reactions, sometimes not all of these microtubes are needed
      at the same time. METHODS: Gelcards "NaCl, enzyme test and cold agglutinins" and
      "Liss/Coombs" were not recentrifuged or 1 to 5 times recentrifuged. Gelcards
      "DiaClon ABD confirmation for patients" were not recentrifuged or recentrifuged
      once before being used for testing. RESULTS: The use of gelcards, recentrifuged
      up to 5 times or recentrifuged 1 time, respectively, before use, provided no
      false positive or false negative results. CONCLUSIONS: Quality assurance of
      gelcards, that had been centrifuged several times before being used for testing,
      is an example for economical and safe use of resources in the laboratory.

PMID- 24660551
TI  - Participation and performance in INSTAND multi-analyte molecular genetics
      external quality assessment schemes from 2006 to 2012.
AB  - BACKGROUND: INSTAND e.V. has provided Molecular Genetics Multi-Analyte EQA
      schemes since 2006. METHODS: EQA participation and performance were assessed from
      2006 - 2012. RESULTS: From 2006 to 2012, the number of analytes in the Multi
      Analyte EQA schemes rose from 17 to 53. Total number of results returned rose
      from 168 in January 2006 to 824 in August 2012. The overall error rate was 1.40
      +/- 0.84% (mean +/- SD, N = 24 EQA dates). From 2006 to 2012, no analyte was
      reported 100% correctly. Individual participant performance was analysed for one
      common analyte, Lactase (LCT) T-13910C. From 2006 to 2012, 114 laboratories
      participated in this EQA. Of these, 10 laboratories (8.8%) reported at least one
      wrong result during the whole observation period. All laboratories reported
      correct results after their failure incident. CONCLUSIONS: In spite of the low
      overall error rate, EQA will continue to be important for Molecular Genetics.

PMID- 24660552
TI  - Blood eosinophil and platelet levels, proteomics patterns of trail and CXCL8
      correlated with survival in bevacizumab treated metastatic colon cancers.
AB  - STrail (soluble TNF-related apoptosis-inducing-ligand) has also been observed
      where the cytotoxic effects of antiangiogenic agents are increased in clinical
      phase II and III studies when these agents are combined with TRAIL related
      therapies. Recent studies have shown that CXCL8 and its receptors are
      significantly up-regulated in CRC and act as regulators of proliferation,
      angiogenesis, and metastasis. sTRAIL, CXCL8, CEA, together with complete blood
      count parameters (hemoglobine, platelet, eosinophil, basophil, neutrophil,
      lymphocyte) were recorded in the beginning and every three months afterwards for
      a period of 4 years. The study population comprised 21 of the 42 patients with
      metastatic colorectal cancer (MCRC), undergoing 18 FDG-PET/CT scanning prior to
      treatment. Progression free survival was 262 days and overall survival was 1148
      days. Overall survival was higher in patients whose Karnofsky Performance scores
      were above 86% (p = 0.003). Progression free survival was higher in patients
      whose blood eosinophil counts at 0, 6, and 9 months were higher than the mean
      levels of corresponding values (p-values are 0.016, 0.032, and 0.001,
      respectively). Another significant positive correlation was found between the
      platelet levels at 9 months and progression free survival (p = 0.019). There were
      significant changes (p < 0.05) prior to treatment and three months later for
      sTRAIL (p = 0.0060) and CXCL8 (p = 0.00001), based on the Wilcoxon matched pairs
      signed rank test. Generally, sTRAIL values increased during therapy, while a
      decrease was observed for CXCL8 without any significant differences for other
      variables.

PMID- 24660553
TI  - [Guidelines for conflict of interest in clinical research].

PMID- 24660554
TI  - [Creation of a scale for evaluating attitudes of partners toward alcohol
      dependency].
AB  - The aim of this study was to develop a scale to evaluate characteristics of how
      alcohol-dependent people perceive the attitudes of their partners toward alcohol
      dependency. Based on previous research, we created the "Attitudes of partners
      toward alcohol dependency" scale, from the perspective of the alcohol dependent
      individual. Using the new scale, 71 alcohol-dependent people (52 men, 19 women)
      were surveyed after obtaining their consent, and the reliability and validity of
      the scale were tested. The results identified 3 factors, "indifference",
      "acceptance" and "hypersensitivity", and factorial validity was verified.
      Relatively high reliability was obtained on each sub-scale (alpha = .60-.82).
      Furthermore, correlations were obtained with the alcohol-dependency "Denial and
      Awareness Scale (for alcohol-dependent people)" and with the 13-item "Usefulness
      of heterosexual love relations for recovery from alcohol dependency"
      questionnaire, which includes content on "beneficial" or "obstructive" to
      recovery, and with the satisfaction and the importance of relations. This
      demonstrates that the "Attitudes of partners toward alcohol dependency" scale has
      reliability and criterion-related validity. The scale facilitates evaluation of
      types of attitudes of partners toward alcohol dependency, and may thus be useful
      as one tool for investigating the influence of partners in heterosexual love
      relationships for recovery, and for providing advice.

PMID- 24660555
TI  - [Survey of institutional staff's views concerning heterosexuality and recovery by
      alcoholics].
AB  - The objective of this study was to identify how staff working in institutions for
      the treatment of and recovery from alcoholism view the relationship between
      heterosexuality and recovery on the part of alcoholics, how they deal with this
      relationship, and issues the staff face. Data were collected from 89 staff
      members (36 men, 52 women, 1 unknown gender) residing in the Kanto region and
      working at hospitals or local institutions. Over half the staff reported dealing
      with the issue of heterosexuality respectfully, but in terms of their views, a
      large majority of the staff was highly concerned about relapse due to
      heterosexuality. Half of the staff believed that heterosexuality might prevent
      continued abstinence. They also believed that the risk of relapse was increased
      further if the period of abstinence was short, the person was unemployed, both
      partners were alcoholics, the person had yet to admit their alcoholism, or if the
      relationship was an extramarital affair or with someone in the early stages of
      recovery. Medical staffs were more likely than other staff to respect the
      heterosexuality of alcoholics while being highly concerned about the risk of
      relapse. The results also showed that as alcoholics were unlikely to refrain from
      heterosexuality even if advised to do so, staff would probably use an appropriate
      method of guidance if one were available. These findings indicate the need to
      develop more practical and firmly held specialist therapies for heterosexuality
      among alcoholics, which has been regarded negatively as frequently leading to
      relapse, based on studies from the perspectives of both alcoholics and staff.

PMID- 24660556
TI  - [The relationship between BDNF gene polymorphisms and alcoholics in Japan].
AB  - As a help of the mechanism elucidation of alcoholism, we studied the relationship
      between brain-derived neurotrophic factor (BDNF) rs6265, 270 C/T (ID number has
      not yet been determined), and rs10835210 gene polymorphisms, which are reported
      to be related to bipolar disorder, and alcoholics. We genotyped the three
      polymorphisms in the BDNF gene using polymerase chain reaction (PCR)-restriction
      fragment length polymorphism (RFLP) in 65 alcoholics and 71 healthy controls. In
      this study, there was no significant difference in the frequency of rs6265 and
      270 C/T polymorphisms between alcoholics and controls (P > 0.05). However, there
      was a significant difference in the genotype frequency of rs10835210 polymorphism
      between alcoholics and controls (P < 0.05), in which the CA heterozygote genotype
      and A allele frequency was higher in alcoholics than in the controls. It suggests
      the possibility that the BDNF rs10835210 gene polymorphism affects the etiology
      of alcoholism.

PMID- 24660557
TI  - [Factors associated with dropout from a group cognitive behavioral therapy for
      substance use disorder].
AB  - BACKGROUND: Dropout represents one of important issues in psychosocial treatments
      for substance use disorders. In Japan, group therapies based on cognitive
      behavioral therapies such as Serigaya Methamphetamine Relapse Prevention Program
      (SMARPP) have been conducted. Little is known, however, about factors associated
      with dropout from group cognitive behavioral therapies for substance use
      disorders. AIMS: The purpose of the present study is to clarify factors which are
      associated with dropout in group cognitive behavioral therapies for substance use
      disorders. In this study, dropout is defined as being absent of the final session
      and attending to less than 9 of 28 sessions. METHODS: Fifty-three patients with
      substance use disorder participated in this study. The group program conducted in
      this study is a group cognitive behavioral therapy. Variables related to
      demographic (age, gender, education level, marital status, and criminal record),
      drug use (age at which s/he used drug and the length during which s/he is
      abstinent from using drugs), and the initial session (mood states before and
      after the session, and satisfaction with the session) were compared between 20
      patients who dropped out (dropout group) and 33 completers (complete group).
      RESULTS: Compared to the participants in the complete group, those in the dropout
      group were more likely to be female and showed a shorter period during which s/he
      had been abstinent from using drugs. CONCLUSION: These results suggest that
      additional attention need to be paid to participant with these characteristics
      for preventing dropout.

PMID- 24660558
TI  - [The association between extracurricular activities and exercise and substance
      abuse among high school students in Japan: results for an aggregate sample from
      the Japanese School Survey Project on Alcohol and Other Drugs in 2004, 2006, and
      2009].
AB  - The purpose of this study was to clarify the subgroup differences in the
      association between participation in school-based extracurricular activities and
      exercise and levels of cigarette, alcohol, or marijuana use during one's lifetime
      and in the past year. This study also sought to determine the optimal
      classification of subgroups based on four variables (participation in school
      based extracurricular activities, exercise, gender, and school year). Data
      consisted of a combined sample (aggregate sample) from the Japanese School Survey
      Project on Alcohol and Other Drugs (JSPAD) conducted in 2004, 2006, and 2009. The
      aggregate sample consisted of 75,726 1st-, 2nd-, and 3rd-year students (37,697
      males and 38,029 females) at full-time high schools nationwide that were selected
      by stratified, single-stage cluster sampling during each survey. The aggregate
      sample combined randomly selected samples of the same size from each year the
      survey was conducted. Results indicated that 63.4% of the entire sample
      participated in school-based extracurricular activities, 64.8% of males did so,
      and 61.9% of females did so. Results also indicated that 66.4% of the entire
      sample exercised outside of PE class, 79.2% of males did so, and 53.8% of females
      did so. In addition, the prevalence of cigarette, alcohol, or marijuana use was
      predicted from the four variables by multiple logistic regression analysis.
      Results yielded optimal subgroups for the prevalence of each drug's use. Results
      revealed (1) that participation in school-based extracurricular activities and
      gender were more predictive, whereas exercise was least predictive, (2) that the
      association between exercise and substance use measures varies subtly for each
      subgroup, suggesting the existence of a great variety of opportunities for high
      school students to exercise, and (3) that school year had a substantial and
      positive effect on drinking among students who actively participated in school
      based extracurricular activities.

PMID- 24660559
TI  - [Relationship between recidivism and self-efficacy among inmates of drug-related
      offences].
AB  - Aims. Treatment programme for drug-related offenders in Japanese prisons is aimed
      at acquiring coping skills for preventing recidivism and improving self-efficacy
      for preventing recidivism. In this study, we examined if improvement of self
      efficacy actually contributes to the prevention of recidivism. Methods. In order
      to measure the relationship between recidivism and self-efficacy, we examined the
      degree of self-efficacy at the beginning and end of the programme, and we
      monitored 144 females upon their release from prison. The women were all
      incarcerated for drug-related offences and had been participated in the self
      efficacy programme. Results. In this study, we obtained the following results: 1)
      Change in self-efficacy through the programme was not statistically significant;
      2) The recidivism rate of inmates with high self-efficacy at the end of the
      program was low; 3) The amount of change in self-efficacy through the programme
      did not affect the recidivism rate. CONCLUSION: Enhancing self-efficacy through
      the programme is effective in preventing recidivism. It is necessary to improve
      the programme.

PMID- 24660560
TI  - The ILD India Registry: a novel tool for epidemiological surveillance of
      interstitial lung disease in India.

PMID- 24660561
TI  - Association of pulmonary tuberculosis and dermatological conditions among
      patients of a rural medical college hospital.
AB  - INTRODUCTION: Pulmonary tuberculosis (PTB) affects a significant proportion of
      the population. There are many contributory aetiological factors common to
      tuberculosis (TB) and dermatological conditions. AIM: To study the spectrum of
      concurrent skin conditions in patients with PTB and to compare with patients
      having other diseases. METHODS: All patients with PTB admitted to our Institute
      during the period of the study were included in the study. A comparable number of
      patients admitted in other departments constituted the control group. All
      patients were screened for skin diseases. RESULTS: There were 498 patients in
      each group, matched for age and gender. There were 126 patients with skin
      conditions in the study group as against 60 patients in the control group.
      Pityriasis versicolor was the commonest skin condition in both the groups.
      Whereas acniform eruptions and pruritis were more common in the control group.
      Pityriasis versicolor, herpes zoster, erythema nodosum and leprosy were
      significantly more frequent among patients. CONCLUSION: There is a high frequency
      of concurrent skin diseases in patient with PTB that should be managed along with
      it.

PMID- 24660562
TI  - Incidence of chronic thrombo-embolic pulmonary hypertension following acute
      pulmonary thrombo-embolism: an Indian perspective.
AB  - Chronic thrombo-embolic pulmonary hypertension (CTEPH) remains a severe disabling
      disease causing a significant amount of mortality and morbidity worldwide. The
      incidence and severity of this condition is quite obscure. The initial inciting
      event, the reason of progression, the natural history of the disease and the
      predictors of adverse outcomes are not yet adequately clarified. From the Indian
      subcontinent, data regarding this disease is limited. But with the advent of the
      multi-detector computed tomography, the understanding of this disease is
      gradually improving. As most of the available data suggests, acute pulmonary
      embolism (PE) as the main initial trigger leading to CTEPH, we prospectively
      analysed all patients being admitted in our hospital with acute PE and followed
      them over a period of one-and-a-half years to determine the incidence of CTEPH in
      this group. This is just an attempt to increase the awareness about the disease
      pattern and determine the rate of progression, risk factors of poor outcome, so
      that early detection and prompt treatment can benefit the patient care.

PMID- 24660563
TI  - A cross-sectional prospective study of pleural effusion among cases of chronic
      kidney disease.
AB  - BACKGROUND: Pleural effusions of diverse aetiologies are encountered in patients
      with chronic kidney disease (CKD). The objectives of the present study were to
      examine the frequency of occurrence, causes, clinical features and management
      strategies of pleural effusion in patients with CKD including renal transplant
      recipients. METHODS: A prospective cross-sectional observational analysis of
      pleural effusion in adult patients with CKD (stages 3 to 5) attending the
      Departments of Nephrology and Respiratory Medicine of a tertiary care institution
      in Eastern India was performed over a period of one year (February 2010 to
      January 2011). RESULTS: Pleural effusion was found in 29 out of 430 patients with
      CKD (6.7%) and in two out of 34 post-renal transplant recipients (5.9%) evaluated
      during the study period. The mean age was 37.35 +/- 1.8 (mean +/- SEM [standard
      error of mean]) with a male to female ratio of 2:1. Exudates and transudates were
      found in equal frequencies. Heart failure was the single most common cause
      (41.9%, 13 of 31). Tuberculosis (TB) (n = 8, 25.8%) and uraemic effusions (n = 6,
      19.4%) were responsible for the majority of exudates. Unilateral effusion with a
      normal heart size had a positive predictive value of 83.3% for non-heart failure
      aetiology. CONCLUSIONS: Symptomatic pleural effusion was present in a small
      proportion of 6.7%; (n = 29) patients with CKD including post-renal transplant
      recipients. Heart failure, TB and uraemic effusions accounted for most of the
      cases. Differentiating TB from uraemic effusion requires a combined clinico
      pathological approach and this differentiation is absolutely necessary for proper
      management.

PMID- 24660564
TI  - Pulmonary hamartoma.

PMID- 24660565
TI  - Tuberculosis lymphadenitis in a well managed case of sarcoidosis.
AB  - Differentiation between tuberculosis (TB) and sarcoidoisis is sometimes extremely
      difficult. Sequential occurrence of sarcoidosis and TB in the same patient is
      uncommon. We present the case of a young man, with a proven diagnosis of
      sarcoidosis who later developed TB after completion of treatment for sarcoidosis.
      A 32-year-old male patient presented with low-grade fever since two months.
      Physical examination revealed cervical lymphadenopathy. Initial fine needle
      aspiration cytology (FNAC) of the cervical lymph node was suggestive of
      granulomatous inflammation; the chest radiograph was normal. Repeat FNAC from the
      same lymph node was suggestive of reactive lymphoid hyperplasia. The patient was
      treated with antibiotics and followed-up. He again presented with persistence of
      fever and lymphadenopathy and blurring of vision. Ophthalmological examination
      revealed uveitis, possibly due to a granulomatous cause. His repeat Mantoux test
      again was non-reactive; serum angiotensin converting enzyme (ACE) levels were
      raised. This time an excision biopsy of the lymph node was done which revealed
      discrete, non-caseating, reticulin rich granulomatous inflammation suggestive of
      sarcoidosis. The patient was treated with oral prednisolone and imporved
      symptomatically. Subsequently, nearly nine months after completion of
      corticosteroid treatment, he presented with low-grade, intermittent fever and a
      lymph node enlargement in the right parotid region. FNAC from this lymph node
      showed caseating granulomatous inflammation and the stain for acid-fast bacilli
      was positive. He was treated with Category I DOTS under the Revised National
      Tuberculosis Control Programme and improved significantly. The present case
      highlights the need for further research into the aetiology of TB and
      sarcoidosis.

PMID- 24660567
TI  - Primary pulmonary diffuse large B-cell non-Hodgkin's lymphoma in a child.
AB  - A 3-year-old girl presented with a history of intermittent fever of six months
      duration associated with respiratory symptoms consisting of recurrent cough,
      fever, wheeze and a suspected history of contact with tuberculosis (TB). Chest
      radiograph revealed pulmonary infiltrates mimicking miliary TB. She was started
      on anti-tuberculous treatment, but in view of clinical deterioration, a further
      work-up including a lung biopsy revealed non-Hodgkin's lymphoma (NHL). This case
      documents the extremely rare occurrence of pulmonary involvement and miliary
      infiltrates on the chest radiograph in NHL.

PMID- 24660566
TI  - An unusual case of invasive Aspergillus ulcerative tracheobronchitis without
      involvement of lung parenchyma in a post-renal transplant patient.
AB  - We present the case of a 54-year-old male, who presented with respiratory
      complaints four months after he underwent renal transplantation. Bronchoscopy
      showed ulcerated mucosa of the left main bronchus and computed tomography (CT) of
      the thorax showed foci of air within the bronchial wall. A biopsy from the lesion
      showed septate fungal hyphae, dichotomously branching at acute angles. A locally
      invasive Aspergillus ulcerative tracheobronchitis with no parenchymal involvement
      is an important cause of tracheobronchitis in post-renal transplant patients. An
      early diagnosis and institution of appropriate treatment can improve the outcome.
      A combination treatment of caspofungin and voriconazole can be considered if
      patient is not responding to voriconazole alone.

PMID- 24660568
TI  - Giant chondrosarcoma of chest wall.
AB  - Primary chest wall tumours are very rare. Chondrosarcoma is the most common
      tumour arising from the chest wall. We describe the occurrence of a slow-growing
      chondrosarcoma arising from the anterior chest wall in a 35-year-old male
      patient. The tumour was resected successfully and chest wall was reconstucted
      with prolene mesh and muscle flap. The patient was discharged uneventfully
      without any respiratory compromise. There was no recurrence after a three-year
      follow-up. Wide surgical resection with chest wall reconstruction appears to be
      the preferred treatment option for this rare tumour of the chest wall.

PMID- 24660570
TI  - Management issues in haemoptysis: more questions than answers.

PMID- 24660569
TI  - Askin tumour: a rare thoracopulmonary tumour in adults.
AB  - Askin tumour, a primitive neuroectodermal tumour of the thoracopulmonary region,
      is a rare tumour presenting in childhood. Its presentation in adults is rare. We
      report a case of an Askin tumour in an adult patient who presented to us with
      worsening breathlessness and vague chest pain. Investigations including
      immunohistochemistry confirmed the diagnosis of Askin tumour.

PMID- 24660571
TI  - [Dental treatment and anti-thrombotic therapy. Part 1: clinical guideline].
AB  - The modern dental treatment plan opens a variety of new surgical rehabilitating
      treatments. Dental implants, socket preservation peri-apical endodontic surgery
      and alveolar bone augmentation were introduced to dentistry within the last three
      decades. The common characteristics of all these treatments are the surgical
      technique involving soft as well as heard tissue. Within the last decade various
      new anti-thrombotic indications for treatments of patients at risk for thrombotic
      events and a new armamentarium of anti-thrombotics techniques were introduced.
      Both medical improvements confront the dental health providers with the problem
      of surgical treatment with the threat of bleeding. The treatment approach is
      based on a tradeoff between major bleeding versus a catastrophic thrombotic
      event. The magnitude of bleeding risk is a summation of the antithrombotic
      treatment and the extant of surgical treatment. In this article we will summarize
      the clinical guidelines of dental treatment for patients under anti-thrombotic
      treatment.

PMID- 24660572
TI  - [Animal experimentation, animal welfare and scientific research].
AB  - Hundreds of thousands of laboratory animals are being used every year for
      scientific experiments held in Israel, mostly mice, rats, rabbits, guinea pigs,
      and a few sheep, cattle, pigs, cats, dogs, and even a few dozen monkeys. In
      addition to the animals sacrificed to promote scientific research, millions of
      animals slain every year for other purposes such as meat and fine leather fashion
      industries. While opening a front against all is an impossible and perhaps an
      unjustified task, the state of Israel enacted the Animal Welfare (Animal
      Experimentation) Law (1994). The law aims to regulate scientific animal
      experiments and to find the appropriate balance between the need to continue to
      perform animal experiments for the advancement of research and medicine, and at
      the same time to avoid unnecessary trials and minimize animal suffering. Among
      other issues the law deals with the phylogenetic scale according to which
      experimental animals should be selected, experiments for teaching and practicing,
      and experiments for the cosmetic industry. This article discusses bioethics
      considerations in animal experiments as well as the criticism on the scientific
      validity of such experiments. It further deals with the vitality of animal
      studies and the moral and legal obligation to prevent suffering from laboratory
      animals.

PMID- 24660573
TI  - [Decoronation: treatment protocol for ankylotic root resorption as a consequence
      of dental trauma].
AB  - Severe dental traumatic injuries, such as the complete displacement of a tooth
      from its socket (Avulsion) or the displacement of a tooth within its socket
      (Intrusive Luxation), may result in extensive injury to the root surface. As a
      result, the root surface injury heals without cementum and there is fusion
      between the alveolar bone and the exposed dentin or anorganic exposed cementum,
      without any attachment apparatus between them. This phenomenon is known as "dento
      alveolar ankylosis" and is accompanied by ankylotic resorption of the root. In a
      process that results subsequent to the ankylosis, the root surface resorbs, and
      this is part of the remodeling of the alveolar bone (ankylotic resorption). When
      the traumatic injury occurs at a young age, lateral and apical growth of the
      alveolar bone continues without continued physiological eruption of the tooth. As
      a result, the position of the ankylotic tooth does not change, and with time
      thetooth appears infra-occluded resulting in severe esthetic and functional
      consequences. Extraction of the ankylotic tooth is difficult and sometimes even
      impossible due to the rigid fusion between the bone and the tooth. In addition,
      attempted extraction of the ankylotic tooth may lead to fracture of the buccal
      plate and resorption of the alveolar bone. Retention of the ankylotic tooth may
      lead to damage in bone deposition in the verticaldimension, leading to
      difficulties in future prosthodonticrehabilitation, research-based information
      has been incorporated

PMID- 24660574
TI  - [Oral health education--are we succeeding with it?].

PMID- 24660575
TI  - Safflower yellow injection combined with conventional therapy in treating
      unstable angina pectoris: a meta-analysis.
AB  - OBJECTIVE: To evaluate the clinical efficacy of safflower yellow injection
      combined with conventional therapy in treating unstable angina pectoris. METHODS:
      We searched online databases: Chinese journal full-text database, China National
      Knowledge Infrastructure, Wanfang database, Chinese journal full-text database,
      Pubmed, ScienceDirect, Embase, and the Cochrane Library with manual-screening of
      relevant literature. Eligible randomized controlled trials (RCT) on angina
      pectoris were included. We conducted meta-analysis using the RevMan 5.1 software
      from The Cochrane Collaboration. We treated the relief rate of angina symptoms
      and electrocardiograph (ECG) as evaluation. RESULTS: Seven articles, including in
      1134 patients, were enrolled after the evaluation. There was no significant
      heterogeneity among the studies (chi2 = 1.08, df = 6, P = 0.98, I2 = 0%). The
      safflower yellow injection with conventional therapy has a higher effective rate
      than the control group in relieving the symptoms of angina pectoris [odds ratio
      (OR)= 2.95, 95% (CI) (1.81, 4.81)] and improving ischemic ECG [OR = 2.85, 95% CI
      (1.67, 4.86)]. The difference was statistically significant in the "80 mg dosage"
      and "100 mg dosage" subgroups (P < 0.05) for improving clinical symptoms and ECG.
      The funnel graphic was nearly symmetrical. Sensitivity analysis suggested that
      the results were stable. CONCLUSION: Safflower yellow injection as an adjunct
      therapy with conventional drugs shows advantages in easing the clinical symptoms
      of unstable angina and improving ECG over basic therapy alone. However, the
      conclusions should be interpreted with care until more high-quality RCTs are
      reported.

PMID- 24660576
TI  - Treatment of constipation-predominant irritable bowel syndrome by focusing on the
      liver in terms of Traditional Chinese Medicine: a meta-analysis.
AB  - OBJECTIVE: To assess the efficacy of Traditional Chinese Medicine (TCM) on
      constipation-predominant irritable bowel syndrome by focusing on the liver.
      METHODS: Databases (domestic and foreign) were searched with the key words
      "irritable bowel syndrome'", "constipation", and "Chinese medicine"; the relevant
      articles were retrieved and evaluated. Cure rate, "remarkable efficacy",
      recurrence rate and the incidence of adverse reactions were the outcome
      indicators. Review Manager ver 5.1 was used for this meta-analysis, and funnel
      plots used to deted publication bias. RESULTS: Nineteen randomized controlled
      trials were included and 1510 patients involved. The treatment guided byTCM based
      on the liver was superior to Western Medicine [odds ratio (OR) = 2.46, 95%
      confidence interval (CI) 1.80, 3.35)], cure rate [OR = 2.61, 95% Cl (1.93,
      3.52)], remarkable efficacy [OR = 2.68, 95% Cl (1.82, 3.95)], recurrence rate [OR
      = 0.19, 95% CI (0.12, 0.29)] and the incidence of adverse reactions [OR = 0.24,
      95% CI (0.09, 0.65)]. However, funnel plots showed publication bias. CONCLUSION:
      Compared with Western Medicine, the treatment of IBS-C based on the liver is
      significantly better but the results must be treated with caution because
      publication bias was recorded.

PMID- 24660577
TI  - Association among lifestyle, clinical examination, polymorphisms in CDH1 gene and
      Traditional Chinese Medicine syndrome differentiation of gastric cancer.
AB  - OBJECTIVE: To explore the association among life-style, clinical examination,
      polymorphisms in CDH1 gene and Traditional Chinese Medicine (TCM) syndrome
      differentiation of gastric cancer (GC). METHODS: A hospital-based population of
      387 GC patients was investigated in Jiangsu province. Relevant information
      regarding lifestyle and clinical examination were collected by a standard
      questionnaire. Four known single nucleotide polymorphisms (SNPs) in CDH1 were
      investigated by polymerase chain reaction-ligation detection reaction methods.
      Statistical analysis was conducted by SPSS 16.0 software. RESULTS: The results
      showed that meal duration and the status of glutamic pyruvic transaminase were
      significantly associated with TCM syndrome differentiation of GC (both P < 0.05).
      None of the four SNPs in the E-cadherin (CDH1) gene achieved significant
      differences in their distributions among the nine syndrome types of GC (both P >
      0.05). However, significant differences were observed in rs13689 genotype
      distributions between several pairs of syndrome types of GC, suggesting that
      rs13689 is correlated with the syndrome differentiation of GC. CONCLUSION:
      Integrated analysis of lifestyle, clinical examination and CDH1 gene
      polymorphisms can contribute to a better understanding of the GC syndrome types
      and may improve the efficacy of interventions by stratifying disease according to
      TCM criteria.

PMID- 24660578
TI  - Reliability and validity of dermatology life quality index: assessment of quality
      of life in human immunodeficiency virus/acquired immunodeficiency syndrome
      patients with pruritic papular eruption.
AB  - OBJECTIVE: To test the reliability and validity of dermatology life quality index
      (DLQI) in simplified Chinese language by assessing the quality of life (QoL) in
      HIV (human immunodeficiency virus)/AIDS (Acquired immunodeficiency syndrome)
      patients with pruritic papular eruption (PPE). METHODS: A study of simplified
      Chinese-version DLQI was carried out in Henan province, China. The reliability
      and validity were tested by means of statistical method. Data were processed with
      SPSS 19.0. RESULTS: One hundred and seven subjects participated in the study and
      106 (99.07%) finished the questionnaire. Eighteen patients were mildly affected;
      62 were moderately affected, 24 were highly affected, and 2 were extremely
      affected. Reliability analysis showed that the split-half reliability coefficient
      of questionnaire was 0.556 and the reliability of the full test estimated with
      Spearman-Brown. correction was 0.7146. The Cronbach alpha was 0.673. According to
      validity analysis, the correlation between the scores of items and the total
      scores ranged from 0.208 to 0.529 (P < 0.05). Three factors were abstracted
      froml0 questions with the principal component analysis and the contribution rate
      of the 3 common factors was 59.95%. CONCLUSION: The simplified-Chinese-version
      DIQL is an acceptable and valid scale for HIV/AIDS patients with PPE. It can be
      used to evaluate the QoL of HIV/AIDS patients with PPE in China.

PMID- 24660579
TI  - Curative effect of heat-sensitive moxibustion on chronic persistent asthma: a
      multicenter randomized controlled trial.
AB  - OBJECTIVE: To compare the curative effects of heat-sensitive moxibustion with
      conventional drugs on chronic persistent asthma and seek a valuable therapy to
      replace Western Medicine. METHODS: The participants in this multi-center,
      randomized, and controlled study were randomly divided into two groups: group A
      (n=144), treated with heat-sensitive moxibustion (50 sessions) and group B
      (n=144), treated with Seretide (salmeterol 50 plg/fluticasone 250 pg, twice a
      day). The scores of asthma control test (ACT), forced expiratory volume in 1
      second (FEV1), peak expiratory flow (PEF), and attack frequency were measured
      after 15, 30, 60, and 90 days of treatment. Patients followed up 3 and 6 months
      after treatment. RESULTS: There was a significant difference (P= 0.0002) in the
      ACT score and lung function between the two groups after 3 months of treatment
      and (P=0.000 03) during the follow-up visits. In addition, heat-sensitive
      moxibustion reduced attack frequency in the period from inclusion to the 6-month
      follow-up visit. CONCLUSION: This study shows that heat-sensitive moxibustion may
      have a comparable curative effect to Seretide (salmetero/fluticasone) on asthma.

PMID- 24660580
TI  - Influence of moxibustion temperatures on blood lipids, endothelin-1, and nitric
      oxide in hyperlipidemia patients.
AB  - OBJECTIVE: To observe the influence of moxibustion temperature on blood lipids,
      endothelin-1 (ET-1), nitric oxide (NO), and ET-1/NO in hyperlipidemia patients.
      METHODS: Forty-two primary hyperlipidemia patients were randomly divided into two
      groups of 21 and treated with moxibustion at different temperatures. Moxibustion
      was performed with the moxa roll 2.5-3.0 cm from the skin in the treatment group
      and 4 cm in the control group, 10 min per point, once every other day. Skin
      temperature was precisely measured with a thermometer during moxibustion. After a
      12-week treatment, seven measurements of blood lipids, ET-1, and NO were
      recorded. RESULTS: Total cholesterol and triglyceride, were lower in the
      treatment group than in the control group (P < 0.05). Serum ET-1 and ET-1/NO was
      obviously lowered in the treatment group (P < 0.001). Moxibustion regulated NO
      and ET-1/NO in the treatment group much better than in the control group.
      CONCLUSION: Moxibustion can regulate blood lipids and clear blood vessels.
      Moxibustion at 45 degrees C has a better effect than moxibustion at 38 degrees C
      on regulating blood lipids and protecting vascular endothelial function,
      indicating that suitable temperature influences the curative effect of
      moxibustion.

PMID- 24660581
TI  - Effect of soothing liver therapy on oocyte quality and growth differentiation
      factor-9 in patients undergoing in vitro fertilization and embryo transfer.
AB  - OBJECTIVE: To investigate the effect of Soothing liver therapy on infertile women
      undergoing in vitro fertilization and embryo transfer (IVF-ET) and to explore its
      mechanism. METHODS: Fifty-eight women with tubal infertility were randomized into
      two groups: 30 in an experimental group treated with Xiaoyao powder (Shugan) plus
      gonadotropin-releasing hormone analog (GnRHa)/follicle-stimulating hormone (FSH)/
      human chorionic gonadotropin (hCG) and 28 in the control group who were treated
      with GnRHa/FSH/ hCG only. The total gonadotropin (Gn) doses required, endometrial
      thickness, oocyte numbers, high quality embryo production rate and pregnancy rate
      of the two groups were compared. The concentration of growth differentiation
      factor-9 (GDF-9) in follicular fluid was detected by western blotting and the
      expression of GDF-9 mRNA in granulosa cells was measured using reverse
      transcription-polymerase chain reaction amplification. RESULTS: In the
      experimental group, the Gn dose was significantly lower than that in the control
      group; the endometrial thickness, high quality embryo production and pregnancy
      rates were significantly higher and the expression of GDF-9 mRNA was also
      significantly higher than in the control group (all P < 0.05). CONCLUSION: Shugan
      treatment can improve the pregnancy rate of women with tubal infertility; its
      mechanism is possibly related to the increased expression of GDF-9 in granulosa
      cells.

PMID- 24660582
TI  - Effectiveness of external Sanjierupi Gao on mastalgia caused by mammary gland
      hyperplasia: a placebo controlled trial.
AB  - OBJECTIVE: To evaluate the curative effect of external application of the Chinese
      drug, Sanjierupi Gao, on mastalgia caused by mammary gland hyperplasia. METHODS:
      This randomized, double-blinded, and placebo controlled study enrolled 260
      patients with mammary gland hyperplasia from five hospitals. Patients were
      randomly and equally divided into a Sanjierupi Gao treatment group and a placebo
      control group. An adhesive plaster was applied to the most painful area on either
      breast for 7 h a day. Treatment lasted for two menstrual cycles without
      application during menstruation. Mastalgia was used as the main index of curative
      effect. The change before and after treatment in days of mastalgia, the time to
      alleviate pain, pain extent, and severe pain scores were observed. RESULTS:
      Compared to the control group, the treatment group had significantly fewer days
      of mastalgia (P < 0.01), a significantly lower severe pain score (P < 0.01), and
      significantly less subjective pain and tenderness (P < 0.05 and P < 0.01,
      respectively). Three days before the follow-up visit, the pain score in the
      treatment group was significantly lower than that in the control group (P <
      0.05). A non-parametric test was used to compare the time to alleviate mastalgia
      between the two groups and found no statistical difference (Z = -0.313, P =
      0.754). CONCLUSION: Application of Sanjierupi Gao can decrease mastalgia duration
      in patients with mammary gland hyperplasia during menstruation and alleviate the
      extent of mastalgia. The time to alleviate pain is psychologically influenced.

PMID- 24660583
TI  - Correlation between lower gastrointestinal tract symptoms and quality of life in
      patients with stable chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To explore correlations between the symptoms of constipation and
      abdominal distention and severity of chronic obstructive pulmonary disease (COPD)
      in patients with stable disease. METHODS: We studied 191 patients with stable
      COPD (according to defined criteria) in this cross-sectional study from four
      three-level class A Chinese medicine hospitals in China. We built an Epidata 3.0
      database and performed statistical analysis with SPSS, version 17.0. We analyzed
      correlations between the frequency of lower gastrointestinal tract symptoms
      (constipation and abdominal distention) and scores for major pulmonary symptoms
      (cough, sputum and wheezing) based on the St. George's Respiratory Questionnaire
      (SGRQ), 6-minute walking distance (6MWD) and frequency of acute exacerbations of
      COPD (AECOPD). RESULTS: In addition to their pulmonary symptoms, 39.79% and
      40.31% of study patients with stable COPD reported constipation and abdominal
      distention, respectively. Scores for major pulmonary symptoms (cough, sputum and
      wheezing), AECOPD and SGRQ values in patients with constipation and abdominal
      distention were significantly greater, and the 6MWD markedly shorter, than in
      those without them. According to Pearson's correlation analysis, there were
      strong correlations between these lower gastrointestinal tract symptoms and
      scores for pulmonary symptoms, SGRQ, 6MWD and AECOPD. CONCLUSION: Lower
      gastrointestinal tract symptoms such as constipation and abdominal distention can
      adversely affect pulmonary symptoms, frequency of acute exacerbations and quality
      of life in patients with stable COPD.

PMID- 24660584
TI  - Curative effect of warming kidney and fortifying spleen recipe on diarrhea
      predominant irritable bowel syndrome.
AB  - OBJECTIVE: To observe the curative effect of a recipe for warming the kidney and
      fortifying the spleen on diarrhea-predominant irritable bowel syndrome (IBS-D).
      METHODS: This multi-center, double-blind, randomized, and controlled trial
      included 240 patients that met the inclusion criterion and were then divided into
      two groups of 120. Patients in the treatment group (group A) took modified Sishen
      Wan orally for warming the kidney and fortifying the spleen and patients in the
      control group (group B) took a placebo, Chao Maiya, for 4 weeks. 28 days after
      withdrawal, there was a 6-month follow-up to observe patient recurrence
      condition. The total effective rate, curative effect, and recurrence rate were
      evaluated after treatment. RESULTS: There was statistical difference (P < 0.01)
      between the two groups in total effective rate (92.24% in the treatment group and
      49.07% in the control group), in curative effect of TCM syndrome (90.52% and
      47.22%, respectively), and in the recurrence rate (15.79% and 56.86%,
      respectively) within 6 months after treatment. CONCLUSION: Modified Sishen Wan,
      for warming the kidney and fortifying the spleen, can effectively treat IBS-D and
      better control its recurrence.

PMID- 24660585
TI  - Effects of Yishenjiangzhuo granules on immunity and bone metabolism in patients
      with stage 3-4 chronic kidney disease.
AB  - OBJECTIVE: To determine the effects of Yishenjiangzhuo granules (YJG) on bone
      metabolism and to explore the changes in levels of bone Gla protein (BGP),
      tartrate-resistant acid phosphatase (TRAP), as well as their relationships with
      levels of B cells, regulatory T cells (Treg) and interleukin (IL)-17 in patients
      with stage 3-4 chronic kidney disease (CKD) before and after treatment. METHODS:
      Fifty-three stage 3-4 CKD patients were divided randomly into two groups: YJG
      treatment and control. Peripheral blood was taken from two groups of CKD patients
      and 21 healthy subjects in the normal group. The parameters determined were the
      levels of CD4+, CD19+, CD19+ CD69+, CD19+ av, Treg (CD4 + CD25 + CD127lo), BGP,
      TRAP, IL-17, calcium, phosphate, blood urea nitrogen, serum creatinine (SCr),
      hemoglobin (Hb) in peripheral blood, and urinary creatinine. Calcium-phosphate
      products and endogenous creatinine clearance rate (CCr) were calculated according
      to standard protocols. RESULTS: In YJG and control groups, SCr levels were
      lowered (P < 0.01) after treatment, whereas CCr (P < 0.05) as well as Hb and
      albumin levels (P < 0.01) were increased. The changes in levels of CCr and SCr in
      the YJG group were more significant. After treatment, CD19+CD69+ and Treg levels
      in the two groups varied (P < 0.01) compared with those of the normal group; the
      level of CD19+ increased but the levels of CD4+ and CD19 + AV decreased (P <
      0.01) in both groups. Compared with the control group, the changes of CD19+ and
      CD19 + AV in the YJG group were more apparent (P < 0.05). Compared with the
      normal group, levels of IL-17 in both groups increased significantly (P < 0.01),
      and the difference in the control group was more significant (P < 0.05). After
      treatment, the TRAP level increased (P < 0.05), but the difference in BGP level
      (P > 0.05) was not significant. CONCLUSION: In stage 3-4 CKD patients, B cells
      and IL-17 participated in the induction of osteoclast activation. YJG could also
      elevate the level of B cells and decrease their apoptosis, but showed no
      significant effects on active B cells, IL-17 or osteoclast activity.

PMID- 24660586
TI  - Distributions of Sasang constitutions and six syndromes in patients with
      functional dyspepsia and healthy subjects.
AB  - OBJECTIVE: To investigated the characteristics of patients with functional
      dyspepsia (FD) in terms of Sasang constitutional medicine. METHODS: A total of
      116 patients with FD were recruited based on diagnosis by gastroscopy and
      symptomatic measurements. The distributions of Sasang constitutions and six
      syndromes in terms of TKM theory in the patients was compared with those from
      1423 healthy subjects. RESULTS: The distribution of Sasang constitutions for the
      patients with FD significantly differed from that for healthy subjects,
      especially among women; 36.7% vs 45.6% for Taeumin, 28.9% vs 33.9% for Soumin,
      and 34.4% vs 20.4% for Soyangin. Our results assumed a high prevalence of
      Soyangin women (around 1.7 folds), and Soumin (45.2%), in particular, had a high
      prevalence of "deficiency and coldness of spleen and stomach" compared with
      Taeumin (14.9%) and Soyangin types (15.7%). CONCLUSION: This study identified a
      trend for the frequency of FD and the Sasang constitutions. The findings may
      provide new ideas for the study of prevention and management of FD,

PMID- 24660587
TI  - A quantification model of Traditional Chinese Medicine syndromes in children with
      idiopathic precocious puberty and early puberty.
AB  - OBJECTIVE: To establish a quantification model of Traditional Chinese Medicine
      (TCM) syndromes by sampling patients undergoing idiopathic precocious puberty
      (IPP) and early puberty. METHODS: A questionnaire for classifying and quantifying
      TCM syndromes was designed and administered. All the results were analyzed; the
      relationship between 3 types of syndrome and 47 symptoms were summated.
      Meanwhile, the frequency distribution of each symptom or sign was aggregated.
      Fuzzy mathematics was used to develop a quantification model ofTCM syndromes.
      RESULTS: We found that precocious puberty had 3 types of syndrome, including
      hyperactivity of fire due to Yin deficiency (Syndrome I), depressed liver Qi
      transforming into fire (Syndrome II), and end retention of damp heat (Syndrome
      III). In the IPP group, Syndrome I was the most common principal syndrome (100%).
      Forty-six patients (43.81%) were diagnosed with Syndrome I accompanied by
      Syndrome II and 11 (10.48%) were diagnosed with Syndrome I accompanied by
      Syndrome III. In the early puberty group, Syndrome I was also the main syndrome
      (98.39%). The degrees of most symptoms were mild to moderate. Reddened tongue was
      the most common tongue manifestation (62.86% prevalence) in the IPP group. The
      most common pulse manifestations were slippery pulse, thread pulse, and taut
      pulse. The Asymptotic Normalization Coefficient (ANC) method was used to quantify
      the TCM syndromes in 167 cases. Diagnostic accuracy rate reached 91%, comparable
      to expert diagnosis. CONCLUSION: We find that there are 3 types of syndrome in
      the IPP group and in the early puberty group. Syndrome I (hyperactivity of fire
      due to Yin deficiency) is the main syndrome in the two groups. ANC may be an
      appropriate for quantification model of TCM syndromes.

PMID- 24660588
TI  - Features analysis on Traditional Chinese Medicine syndromes in patients with
      diabetic peripheral neuropathy.
AB  - OBJECTIVE: To study the features of the distribution and differentiation of
      Traditional Chinese Medicine (TCM) syndromes in patients with diabetic peripheral
      neuropathy (DPN). METHODS: We collected clinical data on illness course, age,
      fasting blood glucose, saccharogenic hemoglobin, TCM syndromes, tongue, and pulse
      of 238 DPN patients. Differentiated main syndromes (Yin deficiency and exuberant
      heat, invasion of spleen by damp-heat, deficiency of both Qi and Yin, and
      deficiency of both Yin and Yang) and accompanying syndromes (blood stasis and
      phlegm-dampness) of diabetes were also recorded. The features of DPN syndromes
      were then analyzed. RESULTS: Among the fourmain syndromes of diabetes, deficiency
      of both Yin and Yang was the most common in the 238DPN patients, of which 89%-96
      had blood stasis. CONCLUSION: The method of differentiating syndromes of diabetes
      can be applied to DPN patients. Deficiency of both Yin and Yang, often
      accompanied by blood stasis, is commonly seen.

PMID- 24660589
TI  - Correlation between tobacco and alcohol use and Traditional Chinese Medicine
      constitutions: an analysis based on a sample from general population of China.
AB  - OBJECTIVE: To investigate the relationship between smoking and drinking and
      constitution types from Traditional Chinese Medicine (TCM) theory. METHODS: The
      Constitution in Chinese Medicine Questionnaire (CCMQ) was used. A sample of 8448
      subjects from nine provinces and municipalities was chosen from the database of
      the TCM constitution and health status survey. Constituent ratio and
      correspondence analysis were used to find the relationship between smoking and
      drinking and TCM constitution. RESULTS: There was an association between smoking
      and drinking and the Gentleness, phlegm-dampness, and dampness-heat type
      constitutions. People that did not smoke tobacco or drink alcohol tended to have
      Yang-deficiency, Yin-deficiency, Qi-depression, Qi-deficiency, special diathesis,
      or blood-stasis type constitutions. CONCLUSION: There was a significant
      correlation between tobacco and alcohol use and TCM constitutions. To improve
      patient health, more attention should be paid to tobacco and alcohol control.

PMID- 24660590
TI  - Biological indicators of sub-optimal health status.
AB  - OBJECTIVE: To investigate biological indicators of sub-optimal health status and
      provide means of objective assessment of sub-optimal health status. METHODS: We
      set the unified standards for diagnosing a SHS. We tested various laboratory
      indicators in 407 cases that we selected randomly from 2807 subjects and
      collected 15 mL of fasting venous blood from each case. We measured serum
      immunoglobulin A (IgA) and immunoglobulin G (IgG) concentrations, serum beta
      endorphins (beta-EP), cortisol (C), testosterone (T), plasma adrenocorticotropic
      hormone (ACTH) and serum T lymphocyte subsets CD3+ and CD4+. RESULTS: Mean serum
      testosterone concentrations and their ratio to cortisol (C) concentrations were
      significantly higher in the healthy group than in those with sub-optimal health
      status (P < 0.01). Mean serum CD3+ concentrations were significantly higher in
      those with sub-optimal health status than in the healthy group (P < 0.05).
      CONCLUSION: Decreased serum testosterone/cortisol ratio may be an objective
      indication of sub-optimal health status. Changes in neuroendocrine and
      immunological indicators may explain some of the symptoms, including malaise and
      poor work performance, attributable to persistent or relapsing fatigue in
      subjects with sub-optimal health status.

PMID- 24660592
TI  - Effect of artemisia species on cellular proliferation and apoptosis in human
      breast cancer cells via estrogen receptor-related pathway.
AB  - OBJECTIVE: To investigate the mechanism underlying the anticancer effect of
      Artemisia species through the inhibition of cell growth and induction of
      apoptosis in breast carcinoma cells. METHODS: To evaluate the anticancer activity
      of methanol extracts of eight Artemisia species (Artemisia stolonifera, Artemisia
      selengensis, Artemisia japonica, Artemisia Montana, Artemisia capillaris,
      Artemisia sylvatica, Artemisia keiskeana, and Artemisia scoparia), we first
      investigated the proliferation of estrogen receptor (ER)-positive MCF-7 breast
      carcinoma cells exposed to 5 or 200 g/mL for 72 h. Apoptosis induction was
      assessed by an Annexin V binding assay in cells exposed to extracts at a high
      concentration (200 g/mL). To verify the mechanism of apoptosis, ER expression and
      its related signaling was investigated using an immunoblot assay under the same
      conditions. RESULTS: MCF-7 cells showed the strongest antiproliferative response
      to the tested extracts. However, a biphasic effect was observed: the extracts
      inhibited proliferation at high concentrations whereas they stimulated it at low
      ones. ER expression was similarly modulated by the extracts. However, all of the
      extracts induced apoptosis at a high concentration (200 g/mL). Compared to the
      control level, exposure to the extracts resulted in a remarkable increase in the
      shift of cell populations. CONCLUSION: The present study suggests that the tested
      Artemisia species exerted their anticancer effects through the induction of
      apoptosis via an ER-related pathway.

PMID- 24660591
TI  - Effect of hypoglycemic anti-deafness capsules in diabetic patients with deafness
      and toxicological assessment in rats.
AB  - OBJECTIVE: Through experiment on animals and clinical trials to explore the
      safety and efficacy of hypoglycemic anti-deafness capsules on diabetic patients
      with deafness. METHODS: Total 296 patients with non-insulin dependent diabetes
      mellitus (NIDDM) were randomly divided into two groups. A treatment group of 164
      patients (208 ears) was treated with hypoglycemic anti-deafness capsules based on
      TCM syndrome differentiation. A control group of 132 patients (184 ears) was
      treated with glibenclamide and conventional drug treatment for deafness. The
      following were observed: hearing, fasting plasma glucose (FPG), 2 h postprandial
      plasma glucose (2hPG), 24 h urine glucose (24hUG), improvement of main symptoms,
      platelet function, and changes in superoxide dismutase (SOD) and lipid peroxide
      (LPO) levels. In animal studies, Kunming mice, weighing 18-22 g were used. Half
      of the mice were males and half were females. Wistar rats, weighing 80-120 g were
      used. Half of the rats were males and half were females. Male Wistar rats,
      weighing 200-220 g, were also used. Their acute and chronic toxicity was studied.
      RESULTS: The hearing improvement was 56.7% in the treatment group and 26.6% in
      the control group. FPG, 2hPG, and 24hUG were improved significantly (P < 0.05, P
      < 0.01, P < 0.01, respectively) in the treatment group and 2hPG and 24hUG
      improved significantly in the control group (P < 0.05, P < 0.05). The improvement
      in 2hPG and 24hUG in the treatment group was significantly greater than that in
      the control group P < 0.01).There was no significant difference in FPG between
      the two groups (P < 0.05). Main symptoms in the treatment group were
      significantly more improved than those in the control group (P < 0.05, P < 0.01).
      In the treatment group, platelet adhesion and aggregation, SOD, and LPO were all
      significantly improved from before treatment (P < 0.05, P < 0.01). However, in
      the control group, except LOP (P < 0.05), there were no significant differences
      from before treatment to after (P < 0.05). In animal studies, no obvious acute or
      long-term toxicity was observed from capsule administration. CONCLUSION: Through
      experiment on animals and clinical trials, we can found that hypoglycemic anti
      deafness capsules could decrease blood glucose and serum triglycerides of alloxan
      induced diabetic rats. This herbal capsule is effective for safely treating
      diabetic patients with deafness.

PMID- 24660593
TI  - Effect of puerarin on matrix metalloproteinase-2 in human fetal scleral
      fibroblasts treated with low frequency electromagnetic fields.
AB  - OBJECTIVE: To study the effect of puerarin on matrix metalloproteinase-2 (MMP-2)
      gene and protein expression in human fetal scleral fibroblasts (HFSFs) exposed to
      extremely low frequency electromagnetic fields (ELF-EMF). METHODS: Cultured HFSFs
      were exposed to 0.2 mT ELF-EMF for 24 h. The experimental groups were divided
      into subgroups treated with 0, 0.1, 1 and 10 microM puerarin respectively. The
      expression of MMP-2 mRNA and protein were detected with real-time polymerase
      chain reaction and western-blot analysis respectively. RESULTS: MMP-2 mRNA and
      protein expression increased by 0.793 and 1.130 folds respectively under the
      exposure of ELF-EMFs at 0.2 mT flux density for 24 h. Puerarin at the
      concentration of 0.1 microM reversed this effect by 8.53% in mRNA and by 17.97%
      in protein expression (P < 0.05). The effect was more prominent at higher
      concentrations (1 and 10 microM, P < 0.01). CONCLUSION: Exposure to ELF-EMFs
      increased the expression of MMP-2 mRNA and protein in HFSF cells. Puerarin
      reversed the action to some extent in a specific concentration range. Our results
      implied that the puerarin might protect scleral tissue from increased expression
      induced by exposure to ELF-EMFs.

PMID- 24660594
TI  - Protective effect of Sijunzi decoction on neuromuscular junction ultrastructure
      in autoimmune myasthenia gravis rats.
AB  - OBJECTIVE: To investigate the protective role of Sijunzi decoction in
      neuromuscular junction (NMJ) and muscle cell mitochondria ultrastructure; as well
      as its effects on the amount of adenosine triphosphate (ATP) and the activities
      of mitochondrial respiratory chain complexes I, II, III, and IV in autoimmune
      myasthenia gravis rats. METHODS: An experimental autoimmune myasthenia gravis
      (EAMG) rat model was established by inoculating rats with acetylcholine receptors
      extracted from Torpedo. Rats were divided into three groups: model, prednisone,
      and Sijunzi decoction, and were fed physiological saline, prednisone, or Sijunzi
      decoction, respectively. NMJ and muscle cell mitochondria ultrastructure were
      observed by transmission electron microscope. The amount of ATP was assessed by
      high performance liquid chromatography. The activities of mitochondrial
      respiratory chain complexes I, II, III, and IV was determined using the Clark
      oxygen electrode method. RESULTS: In the model group, there were sparse muscle
      fibers, with decreased mitochondria, and sparse, diffluent, or absent NMJ folds.
      After intervention with Sijunzi decoction, the above pathology changes were
      improved: muscle fiber structure was clear and complete; the mitochondria count
      was higher; and the NMJ structure was close to normal. Gastrocnemius muscle
      mitochondria in the model group produced significantly less ATP than those in the
      prednisone group (P < 0.01). Conversely, the ATP of Sijunzi decoction group was
      significantly higher than prednisone group (P < 0.01). The activities of
      gastrocnemius muscle mitochondrial respiratory chain complexes I, II, III, and IV
      in both the prednisone and Sijunzi decoction groups was dramatically higher
      compared with the model group (P < 0.05). The activities of complexes I and III
      in the Sijunzi decoction group were significantly higher than those in the
      prednisone group (P < 0.05), but there was no obvious difference in complex II or
      IV activities between the two groups (P > 0.05). CONCLUSION: Sijunzi decoction
      improved pathological changes in muscle mitochondria and NMJ, enhanced the amount
      of ATP in gastrocnemius muscle mitochondria, and improved the activities of
      respiratory chain complexes I, II, III, and IV (especially I and III) of the EAMG
      rats.

PMID- 24660595
TI  - Effects of Sini San used alone and in combination with fluoxetine on central and
      peripheral 5-HT levels in a rat model of depression.
AB  - OBJECTIVE: To investigate the effects of Sini San and fluoxetine on the levels of
      central and peripheral 5-HT in a rat model of depression, and provide new insight
      into the treatment of depression with integrated Chinese-Western Medicine.
      METHODS: A rat model of depression was established by chronic mild stress (CMS).
      Model rats received either Sini San, fluoxetine, a combination of the two drugs,
      or no drug treatment. Healthy naive rats were used as controls. Open field and
      sucrose preference tests were used to assess depression-like behavior. ELISA and
      immunohistochemistry were used to determine central and peripheral levels of 5
      HT. RESULTS: In the group with no drug treatment, central 5-HT expression
      decreased while peripheral 5-HT concentrations increased as CMS continued. Four
      weeks after CMS, Sini San alone was less effective in reducing depression-like
      behavior than fluoxetine alone or in combination with Sini San, but combined use
      was more effective than fluoxetine alone. Eight weeks after CMS, Sini San alone
      or in combination with fluoxetine was more effective in reducing depression-like
      behavior than fluoxetine alone. Furthermore Sini San and fluoxetine used alone or
      in combination notably increased central 5-HT expression and decreased peripheral
      5-HT levels in the rat model. CONCLUSION: The results of the present study
      indicate that there is a synergistic action between the two medicines in the
      treatment of depression. Sini San exhibited a relatively long lag before its
      effects were observed; however, by eight weeks the Traditional Chinese Medicine
      appeared at least as effective as fluoxetine. We suggest that Sini San can
      replace fluoxetine in the later stages of depression treatment to minimize side
      effects observed with long-term fluoxetine administration.

PMID- 24660596
TI  - Optimization of vinegar-steaming process for Wuweizi (Fructus Schisandrae
      Chinensis) with response surface method.
AB  - OBJECTIVE: To optimize the vinegar-steaming process of Wuweizi (Fructus
      Schisandrae Chinensis) using the response surface method (RSM) based on the Box
      Behnken design. METHODS: A regression model was constructed with the response
      variables, the content of Deoxyschizandrin, and the three explanatory factors:
      length of steaming time, the quantity of vinegar and length of moistening time to
      evaluate the effects on the processing of Wuweizi (Fructus Schisandrae
      Chinensis). RESULTS: There was a linear relationship between the content of
      Deoxyschizandrin and the three explanatory factors. When the steaming time was
      5.49 h, with 2.365 g of vinegar added and a moistening time of 4.13 h, the
      content of Deoxyschizandrin reached the maximum predicted value of 0.1076%, and
      under the conditions the average content of Deoxyschizandrin was 0.1058%.
      CONCLUSION: The correlation coefficient of the nonlinear mathematical model was
      relatively high and the model matched the data well, potentially providing a
      method for the study of the steaming process.

PMID- 24660597
TI  - Component analysis of Chinese medicine and advances in fuming-washing therapy for
      knee osteoarthritis via unsupervised data mining methods.
AB  - OBJECTIVE: To analyze the component law of Chinese medicines in fuming-washing
      therapy for knee osteoarthritis (KOA), and develop new fuming-washing
      prescriptions for KOA through unsupervised data mining methods. METHODS: Chinese
      medicine recipes for fuming-washing therapy for KOA were collected and recorded
      in a database. The correlation coefficient among herbs, core combinations of
      herbs, and new prescriptions were analyzed using modified mutual information,
      complex system entropy cluster, and unsupervised hierarchical clustering,
      respectively. RESULTS: Based on analysis of 345 Chinese medicine recipes for
      fuming-washing therapy, 68 herbs occurred frequently, 33 herb pairs occurred
      frequently, and 12 core combinations were found. Five new fuming-washing recipes
      for KOA were developed. CONCLUSION: Chinese medicines for fuming-washing therapy
      of KOA mainly consist of wind-dampness-dispelling and cold-dispersing herbs,
      blood-activating and stasis-resolving herbs, and wind-dampness-dispelling and
      heat-clearing herbs. The treatment of fuming-washing therapy for KOA also
      includes dispelling wind-dampness and dispersing cold, activating blood and
      resolving stasis, and dispelling wind-dampness and clearing heat. Zhenzhutougucao
      (Herba Speranskiae Tuberculatae), Honghua (Flos Carthami), Niuxi (Radix
      Achyranthis Bidentatae), Shenjincao (Herba Lycopodii Japonici), Weilingxian
      (Radix et Rhizoma Clematidis Chinensis), Chuanwu (Radix Aconiti), Haitongpi
      (Cortex Erythrinae Variegatae), Ruxiang (Olibanum), Danggui (Radix Angelicae
      Sinensis), Caowu (Radix Aconiti Kusnezoffii), Moyao (Myrrha), and Aiye (Folium
      Artemisiae Argyi) are the main herbs used in the fuming-washing treatment for
      KOA.

PMID- 24660598
TI  - Case-based learning in education of Traditional Chinese Medicine: a systematic
      review.
AB  - OBJECTIVE: To assess the effect of case-based learning (CBL) in the education of
      Traditional Chinese Medicine (TCM). METHODS: The studies concerning TCM courses
      designed with CBL were included by searching the databases of EBSCO, Pubmed,
      Science Citation Index, China National Knowledge Infrastructure, Chongqing VIP
      database. The valid data was extracted in accordance with the included criteria.
      The quality of the studies was assessed with Gemma Flores-Masteo. RESULTS: A
      total of 22 articles were retrieved that met the selection criteria: one was of
      high quality; two were of low quality; the rest were categorized as moderate
      quality. The majority of the studies demonstrated the better effect produced by
      CBL, while a few studies showed no difference, compared with the didactic format.
      All included studies confirmed the favorable effect on learners' attitude, skills
      and ability. CONCLUSION: CBL showed the desirable results in achieving the goal
      of learning. Compared to didactic approach, it played a more active role in
      promoting students' competency. Since the quality of the articles on which the
      study was based was not so high, the findings still need further research to
      become substantiated.

PMID- 24660599
TI  - Expert knowledge maps for knowledge management: a case study in Traditional
      Chinese Medicine research.
AB  - OBJECTIVE: To design a model to capture information on the state and trends of
      knowledge creation, at both an individual and an organizational level, in order
      to enhance knowledge management. METHODS: We designed a graph-theoretic knowledge
      model, the expert knowledge map (EKM), based on literature-based annotation. A
      case study in the domain of Traditional Chinese Medicine research was used to
      illustrate the usefulness of the model. RESULTS: The EKM successfully captured
      various aspects of knowledge and enhanced knowledge management within the case
      study organization through the provision of knowledge graphs, expert graphs, and
      expert-knowledge biography. CONCLUSION: Our model could help to reveal the hot
      topics, trends, and products of the research done by an organization. It can
      potentially be used to facilitate knowledge learning, sharing and decision-making
      among researchers, academicians, students, and administrators of organizations.

PMID- 24660600
TI  - Safety and efficacy of Danqipiantan capsule for treatment of stroke: a systematic
      review.
AB  - OBJECTIVE: To evaluate the efficacy and safety of Danqipiantan capsule (DPC) for
      the treatment of stroke. METHODS: PubMed, China Science And Technology Journal
      Database, Wanfang Database, Chinese periodicals in the China National Knowledge
      Infrastructure, and the General Hospital of Tianjin Medical University's Library
      were searched until July 2012. Randomized controlled trials (RCTs) and
      observational studies that reported the use of DPC for treatment of stroke were
      selected. RESULTS: Eleven articles that included 12 RCTs, and 2 articles that
      included 3 observational studies were identified. A total of 2590 patients
      participated inthe studies. We found that there was a signficant statistical
      difference between DPC treatment groups and the control groups in terms of the
      effective rate [risk ratio (RR), 1.14; 95% confidence intervals (CI), 1.04, 1.25;
      P = 0.01], Fugl-Meyer Assessment Scale [weighted mean difference (WMD), 9.77; 95%
      C (4.84, 14.70); P = 0.00], Barthel Index [WMD = 6.40; 95% Cl (3.15, 9.65)], and
      mean flow velocity [WMD = 5,79; 95% CI (1.64, 9.94)]. There were no significant
      differences for The National Institutes of Health Stroke Scale [WMD = 0.60; 95%
      CI (-1.09, 2.29)], visual field defects [left visual field: WMD = -203.10; 95% CI
      (-424.41, 18.21); right visual field: WMD = -172.60; 95% CI (-409.29, 64.09)] or
      the functional independence measure [WMD = -7.90; 95% Cl (-16.64, 0.84)]. Seven
      articles that included eight RCTs reported the safety of DPC treatment. Two
      articles that included three observational studies also reported beneficial
      effects for DPC. Because the Chinese studies were of poor methodological quality,
      and most of the sample sizes were small, our analysis was likely affected by
      bias. CONCLUSION: DPC has a beneficial effect and is relatively safe when used
      for the treatment of stroke.

PMID- 24660601
TI  - Medium- and long-term efficacy of ligustrazine plus conventional medication on
      ischemic stroke: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the medium- to long-term efficacy of ligustrazine plus
      conventional medicine treating ischemic stroke. METHODS: Randomized controlled
      trials (RCTs) testing ligustrazine in the treatment of acute ischemic stroke were
      retrieved from Cochrane Library, PubMed, Excerpta Medica Database, Chinese
      Medical Journal Database, Chinese Biomedical Database, China National Knowledge
      Infrastructure Database, and Chinese Clinical Trial Register, and then identified
      by the inclusive and exclusive criteria. The quality of trials was assessed with
      the Cochrane Handbook 5.1, a risk of bias assessment tool. RevMan 5.1 was used
      for meta-analysis. RESULTS: Three RCTs involving 643 patients were included.
      Compared to conventional medicine treatment alone, ligustrazine plus conventional
      medicine treatment showed significant difference in reduction of stroke
      recurrence either at the end of 1-year follow-up [RR = 0.42, 95% CI (0.18, 0.94),
      P < 0.05] or 3-years observation [RR = 0.48, 95% CI (0.27, 0.83), P < 0.05]. The
      ligustrazine group also showed higher survival rate [RR =1.67, 95% II (1.02,
      0.2.71), P <0.05] and significantly better effective rate [R R= 1.28, 95% II
      (1.10, 1.50), P <0.05] than that of the control group at the end of 1 year visit.
      Only one trial conducted safety assessment and no adverse events were reported.
      The methodological quality of all the trials included was generally poor.
      CONCLUSION: The findings provided evidence that the combination of ligustrazine
      and conventional medication was medium- and long-term beneficial to the patients
      suffering ischemic stroke. But more RCTs of high quality are needed to further
      prove the efficacy and safety of using ligustrazine for ischemic stroke.

PMID- 24660602
TI  - Efficacy of Chinese herbal medicine for lumbar disc herniation: a systematic
      review of randomized controlled trials.
AB  - OBJECTIVE: This is a review of the effects of Chinese herbal medicine (CHM) used
      alone to treat lumbar disc herniation (LDH). METHODS: A literature search of the
      following electronic databases from their inception to February 2013 was
      conducted: Chinese Biomedical databases, Chinese National Knowledge
      Infrastructure, Wanfang Database, China Science and Technology Journal Database,
      Cochrane Library, Web of Science, MEDLINE, and EMBASE. Randomized controlled
      trials where CHM had been used to treat LDH were selected. Data extraction,
      quality assessment, and data analysis were carried out by two independent
      reviewers. RESULTS: Of the 2415 studies identified, eight with complete data on
      1146 patients were selected. The methodological quality was poor in all trials.
      Five studies reported that CHM was better than Western Medicine [OR = 2.81, 95%
      CI (1.27, 6.18); OR = 3.34, 95% CI (1.92, 5.79); OR = 2.22, 95% CI (1.08, 4.57);
      OR = 6.67, 95% CI (1.34, 33.28); and OR = 1.94, 95% CI (1.23, 3.06)]. Two studies
      reported that the clinical outcome was better in CHM groups than in physiotherapy
      and placebo groups, [OR = 3.02, 95% CI (1.08, 8.46); and OR = 2.67, 95% CI (1.26,
      5.64), respectively], whereas one study reported no difference between CHM and
      physiotherapy groups. One study reported that CHM resulted in higher Japanese
      Orthopedic Association scores [MD = 7.78, 95% CI (6.67, 8.89)] than in a control
      group and another that participants treated with CHM had lower Visual Analogue
      Scale scores [MD = -0.72, 95% CI (- 0.86, -0.58)] than those in a control group.
      Three studies reported that the adverse effects of CHM and Western Medicine did
      not differ significantly [OR = 0.10, 95% Cl (0.01, 1.85); OR = 0.19, 95% CI
      (0.01, 4.07); and OR = 0.07, 95% CI (0.00, 1.32)]. CONCLUSION: CHM may be more
      effective than other interventions for LDH; however, methodological weaknesses in
      the studies assessed in this review prevent a definitive conclusion. More high
      quality large-scale studies are required to clarify this matter.

PMID- 24660603
TI  - Regulatory effects of stage-treatment with established Chinese herbal formulas on
      inflammatory mediators in pediatric asthma.
AB  - OBJECTIVE: To explore the regulatory effects of established Chinese herbal
      formulas on inflammatory mediators released during asthma attacks, and to
      elucidate the molecular mechanism of Traditional Chinese Medicine in the
      treatment of asthma. METHODS: Seventy-five asthmatic children were randomly
      divided into a Chinese medication group (45 cases) and a Western medication
      control group (30 cases). Patients in the Chinese medication group were treated
      with a series of established Chinese herbal formulas, whereas the Western
      medication control group received a leukotriene receptor antagonist and a
      bronchial relaxant. Real-time PCR was used to determine the mRNA expression
      levels of interleukin (IL)-4, cysteinyl leukotriene receptor 1 (CysLTR1), and
      interferon (IFN)-gamma in peripheral blood mononuclear cells before and after
      treatment. Enzyme-linked immunosorbent assay was used to measure the peripheral
      blood levels of IL-4, leukotriene (LTE)-4, and INF-gamma before and after
      treatment. RESULTS: After treatment, the mRNA expression levels of IL-4 and
      CysLTR1 were down-regulated (P< 0.01) and the mRNA expression levels of IFN-gamma
      were up-regulated (P < 0.05) in the Chinese medication and Western medication
      groups; no significant difference was found between the two groups. In the
      Chinese medication group, IL-4 blood level was decreased and it was significantly
      different from that in the Western medication group (P < 0.05); there was also a
      significant increase in IFN-gamma blood levels after treatment with Chinese
      medication (P < 0.05). There were no significant differences in LTE-4 blood
      levels between the two groups before and after treatment (P > 0.05). CONCLUSION:
      Chinese medication has a regulatory effect on leukotriene receptor gene
      expression and the imbalance of Th1/Th2 immune cells during asthma attacks in
      pediatric patients.

PMID- 24660604
TI  - Reduning injection for fever, rash, and ulcers in children with mild hand, foot,
      and mouth disease: a randomized controlled clinical study.
AB  - OBJECTIVE: To assess the efficacy and safety of Reduning injection for fever,
      rash, and ulcers in children with mild hand, foot, and mouth disease (HFMD).
      METHODS: A stratified-block randomized, double-blind, parallel-controlled, and
      multicenter clinical trial was conducted with 360 patients in five hospitals
      across China: Quanzhou Children's Hospital, Shijiazhuang No. 5 Hospital, Shanghai
      Public Health Centre, Hunan Provincial Children's Hospital, and Kaifeng
      Children's Hospital. Patients were randomized into three groups with 120 in each.
      Group A was treated with Western Medicine, group B with Reduning injection, a
      Chinese herbal medicine, and group C with both Reduning injection and Western
      Medicine. Results were compared for treatment efficacy and safety on HFMD. The
      clinical outcomes were observed as follows: fever and onset time of antifebrile
      effect (time to bring the body temperature down > or = 0.5 degrees C after
      medication); cumulative time for fever recovery (body temperature recovering to
      normal and lasting more than 24 h without medication); cumulative time for rash
      disappearance (without new rashes or ulcers appearing and the original ones
      fading away); and cumulative time for mouth ulcer disappearance. RESULTS: For the
      onset time of the antifebrile effect, there was no statistical difference between
      groups A and B (P > 0.05) and groups B and C (P > 0.05). However, there was a
      statistical difference between groups A and C (P < 0.05), and the effect in group
      C was the best. For the cumulative time for rash disappearance, there was no
      statistical difference between groups A and B (P > 0.05). There were statistical
      differences between groups A and C, and groups B and C (P < 0.05), and the effect
      in group C was the best. For the cumulative time for mouth ulcers disappearance,
      there were no statistical differences among the three groups (P > 0.05).
      CONCLUSION: Reduning injection with Western Medicine for symptomatic treatment is
      most effective for mild HFMD. No adverse reactions were observed.

PMID- 24660605
TI  - Curative effect of Xuebijing injection on severe pulmonary contusion.
AB  - OBJECTIVE: To investigate the curative effects of Xuebijing (XBJ) injection, a
      Chinese patent medicine, on severe pulmonary contusion (PC). METHODS: Sixty-three
      patients with PC were randomized to conventional therapy plus XBJ injection (n =
      33) or conventional therapy alone (n = 30). Between groups differences in
      corticosteroid treatment, immune regulation therapy, hemofiltration, infusion
      volume, transfusion volume and antibiotic period were measured, as were intensive
      care unit (ICU)-free time, ventilation time, 28-day mortality rate and incidence
      of ventilation-associated pneumonia (VAP). Serum concentrations of procalcitonin
      (PCT), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10,
      white blood cell (WBC) counts and percentages of human leukocyte antigen DR/
      CD14+ (HLA-DR/CD14+) peripheral blood mononuclear cells were compared. Markers of
      ventilation were determined by blood gas analysis and ventilator parameters.
      RESULTS: WBC counts and serum concentrations of PCT, TNF-alpha, IL-6 and IL-10
      were reduced significantly more quickly, and CD14+ percentage was increased
      significantly earlier, in the XBJ group than in the control group (P < 0.05
      each).The level of ventilation and oxygenation index were ameliorated earlier in
      the XBJ than in the control group (P < 0.05). XBJ treatment significantly reduced
      ICU-free time, ventilation time and incidence of VAP (P < 0.05 each), but had no
      effect on 28-day mortality rate CONCLUSION: XBJ treatment can shorten ICU-free
      and ventilation times and reduce the incidence of VAP, improving outcomes in
      patients with severe PC. XBJ may act by regulating inflammation and immunity,
      alleviating systemic inflammatory response syndrome induced by trauma.

PMID- 24660606
TI  - Effect of acupuncture anesthesia on acne vulgaris of pricking-bloodletting
      cupping: a single-blind randomized clinical trail.
AB  - OBJECTIVE: To evaluate the effect on acne vulgaris of pricking-bloodletting
      cupping at Dazhui (GV 14) under acupuncture anesthesia, and establish whether
      providing anesthesia to the treatment area by manipulating Hegu (LI 4) and Quchi
      (LI 11) might have an additional therapeutic benefit. METHODS: Thirty-eight
      patients were recruited and randomized into a control group and an intervention
      group with a single-blind (observer-blind) method. The control group was treated
      by pricking-bloodletting cupping at Dazhui (GV 14)-and the studied group by
      pricking-bloodletting cupping at Dazhui (GV 14) under acupuncture anesthesia at
      Hegu (LI 4) and Quchi (LI 11). Both groups were treated twice weekly for 6 weeks.
      The analgesic and therapeutic effects of acupuncture were evaluated on a visual
      analog scale (VAS) and global acne grading system (GAGS), respectively. RESULTS:
      There were differences in the VAS scores of pain on pricking and in the pricked
      area, and the duration of pain between the groups. After 12 treatments, there was
      a significant reduction in GAGS scores from baseline in both groups, but there
      was no significant difference between the groups. CONCLUSION: Acupuncture
      anesthesia at Hegu (LI 4) and Quchi (LI 11) is an effective means of alleviating
      the pain of pricking-bloodletting cupping and reducing the duration of pain in
      the treatment area. Pricking-bloodletting cupping at Dazhui (GV 14) improves the
      skin lesions of patients with moderate acne vulgaris, but acupuncture anesthesia
      does not appear to have an additional therapeutic effect.

PMID- 24660607
TI  - Capillary blood flow in patients with dysmenorrhea treated with acupuncture.
AB  - OBJECTIVE: To observe capillary blood flow at acupoints during acupuncture
      treatment of primary dysmenorrhea and gain new insights into its analgesic
      mechanism. METHODS: Patients with primary dysmenorrhea were enrolled and randomly
      assigned to a treatment or control group. Subjects' symptoms were differentiated
      into various Traditional Chinese Medicine (TCM) syndromes and treated for 10
      sessions with puncturing acupuncture or self-pressing right-hand Hegu (LI 4),
      adding other acupoints based on syndrome. Laser speckle was used to compare the
      change in the vasomotor amplitude and perfusion of the capillaries in Hegu (LI 4)
      before and during the treatment. Each subject was required to finish the period
      pain symptoms observation form, verbal rating scales, numerical rating scale,
      pain rating index, face rating scale, Zung self-rating depression scale, Zung
      self-rating anxiety scale, and numerical rating scale before and after
      treatments. RESULTS: After 10 sessions, the symptom scores, pain index (PI), and
      visual analog scale (VAS) decreased significantly in treatment group. The volume
      of blood flow in Hegu (LI 4) declined slightly. No significant evidence supported
      that needling caused capillary contraction, but the capillary vasomotor amplitude
      at Hegu (LI 4) increased remarkably. CONCLUSION: Acupuncture can increase the
      capillary blood flow, thus promoting the flow of Qi and blood in terms ofTCM
      theory, which facilitates pain relief.

PMID- 24660608
TI  - Correlation between acne and northwest dryness syndrome in Xinjiang autonomous
      region of China.
AB  - OBJECTIVE: To analyze the correlation between acne and Northwest dryness syndrome
      in the Xinjiang region to provide an epidemiological foundation for the
      prevention and treatment of acne in the region. METHODS: The correlations among
      acne, clinical syndromes of Northwest dryness syndrome, and Northwest dryness
      syndrome were evaluated using the syndrome fitness index and canonical
      correlation analysis. syndrome rate of 24.13%, and the control group 10.34% (chi2
      = 7.733, P < 0.01). There was no significant difference in the fitness index for
      acne and for the sub-syndromes of Northwest dryness syndrome (P > 0.05). The
      first canonical correlation coefficient was 0.5656 (P < 0.01). The acne-dependent
      variable group had the largest damp-heat syndrome load (0.8709), and the
      independent variable had the largest lung-heart-spleen pyretic dryness load
      (0.6766). CONCLUSION: Northwest dryness syndrome is a risk factor for acne in the
      Xinjiang region. Exogenous dryness and endogenous damp are frequently seen as
      subsyndromes in Northwest dryness syndrome in acne patients in the region. Acne
      was correlated with the damp-heat and lung-heart-spleen pyretic dryness sub
      syndromes of Northwest dryness syndrome.

PMID- 24660609
TI  - Successful treatment of latent autoimmune diabetes in adults with traditional
      Chinese medicine: a case report.
AB  - INTRODUCTION: Latent autoimmune diabetes in adults (LADA) is regarded as one of
      the Insulin-dependent diabetes mellitus that progress slowly. It gradually became
      understood since 1970s. The onset usually appears in adulthood, the islet
      autoantibodies are positive and the function of beta cell is declined rapidly.The
      treatment is insulin injection. CASE PRESENTATION: The case reported followed is
      a 37-year-old male patient who was newly diagnosed with type 2 diabetes. He
      abandoned oral hypoglycemic agents since they caused stomach indisposed. Before
      visiting, his islet autoantibodies were detected positive and he had never
      injected insulin before. We treated him with traditional Chinese herbals under
      the guidance of Traditional Chinese Medicine and differentiation, and achieved
      fine efficacy. CONCLUSION: Because the initial presentation of LADA is similar to
      Type 2 Diabetes Mellitus and examination is not in common use, misdiagnosis is
      not rare. Once LADA is diagnosed, the therapy must be adjusted. This case report
      indicated that Traditional Chinese Medicine might be an alternative treatment for
      LADA.

PMID- 24660610
TI  - Anti-breast cancer effects and mechanisms of Xihuang pill on human breast cancer
      cell lines.
AB  - OBJECTIVE: To investigate the anti-breast cancer (BC) effects and mechanisms of
      action of Xihuang pill (XHP) by conducting in vitro experiments on human BC cell
      lines. METHODS: Two human BC cell lines (MCF-7 and MDA- MB231) were cultured and
      treated with XHP. Cell viability was detected using the 3-(4, 5-Dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was used to
      measure the cell cycle and apoptosis. The cell cycle was analyzed with propidium
      iodide staining. Apoptosis was evaluated using the Annexin V-fluorescein
      isothiocyanate/propidium iodide method. Western blotting was used to analyze the
      expression of estrogen receptor (ER)-alpha and ER-beta. RESULTS: XHP had growth
      inhibitory effects on MCF-7 and MDA-MB231 cells with a half-maximal inhibitory
      concentration (IC50) of 10.14 mg/mL (MCF-7) and 8.98 mg/mL (MDA-MB231). Apoptosis
      was induced to some extent. Certain changes in the ER were caused. Upregulation
      of ER-a protein was found in MCF-7 cells. ER-beta expression in MDA-MB231 cells
      was increased. Cell-cycle arrest was not observed in the two BC cell lines. ER-1
      expression in MCF-7 cells was unchanged. No ER-a expression was shown in MDA
      MB231 cells. CONCLUSION: These data suggest that XHP can affect cell viability
      and cause apoptosis, but that the cell cycle is not blocked. XHP has a certain
      impact on ER expression, but its mechanisms of action of anti-BC effects may not
      be due to regulation of ER expression.

PMID- 24660611
TI  - Combinatorial effects of conception and governor vessel electroacupuncture and
      human umbilical cord blood-derived mesenchymal stem cells on pathomorphologic
      lesion and cellular apoptosis in rats with cerebral ischemia/reperfusion.
AB  - OBJECTIVE: To investigate the combinatorial effects of conception and governor
      vessel electroacupuncture (EA) and human umbilical cord blood-derived mesenchymal
      stem cells (HUCB-MSCs) on pathomorphologic lesion and cellular apoptosis in rats
      with cerebral ischemia/reperfusion. METHODS: With the HUCB-MSCs isolated,
      cultured and identified and the models of cerebral ischemia-reperfusion
      established, the HUCB-MSCs of passage three were intracranially transplanted and
      the EA at conception and governor vessels was applied. The pathomorphologic
      lesion by hematoxylin-eosin staining and the cellular apoptosis by terminal
      deoxynucleotidyl transferase-mediated nick-end labeling method around the
      ischemic focus were observed. RESULTS: The cultured adherent HUCB-MSCs exhibited
      a spindle shape and expressed MSC-specific markers, with the cell purity and
      proliferation rate significantly increasing after the primary passage. HE
      staining showed that there were no pathological changes observed in the sham
      surgery group. However, in the PBS transplantation group, degeneration and
      necrosis of a great number of nerve cells were seen. In both the HUCB-MSCs
      transplantation group and the HUCB-MSCs transplantation + EA group, reparative
      changes of the pathomorphism of the tissue were found. Both combination treatment
      and simple MSCs treatment were able to improve the pathomorphorlogic lesion
      following cerebral ischemia and reduce the abnormal TUNEL-positive numbers, with
      former better than latter. CONCLUSION: HUCB-MSCs improve pathological lesions and
      inhibit the cellular apoptosis around the cerebral ischemic area. EA at
      conception and governor vessels also improve pathological lesion and inhibit the
      cellular apoptosis in rats treated with HUCB-MSCs transplantation, which effects
      were superior to that of simple HUCB-MSCs transplantation.

PMID- 24660612
TI  - Effect of Xixin decoction on phosphorylation toxicity at specific sites of tau
      protein in brains of rats with sporadic Alzheimer disease.
AB  - OBJECTIVE: To explore the mechanism of action of Xixin decoction (XXD) for the
      prevention and treatment of sporadic Alzheimer disease (SAD) by investigating the
      effects of XXD on the phosphorylation of Thr231 and Ser422 sites of tau protein.
      METHODS: Specific pathogen-free (SPF) male Sprague-Dawley (SD) rats with SAD were
      randomly divided into six groups: sham-operated, model (intracerebroventricular
      injection of Streptozotocin, ICV-STZ), donepezil (0.92 mg/kg), XXD low-dose (7.61
      g/kg(-1) x d(-1)), moderate-dose (15.21 g/kg(-1) x d(-1)), and high-dose (30.42
      g/kg(-1) x d(-1)). Immunohistochemistry and western immunoblotting were used to
      detect the phosphorylation at Thr231 and Ser422 sites of tau protein. RESULTS:
      XXD different dose groups decreased to varying degrees the expression of
      phosphorylated tau at P-Thr231 and P-Ser422 sites in the hippocampus of SAD rats.
      No significant difference was found between the donepezil and model group.
      CONCLUSION: XXD may prevent SAD pathological progress by inhibiting
      hyperphosphorylation at the key sites of tau proteins.

PMID- 24660613
TI  - Pretreatment with Jieduxiezhuo decoction impedes elevations in serum uric acid
      levels in mice.
AB  - OBJECTIVE: To investigate whether Jieduxiezhuo decoction (JDXZD) can prevent
      serum uric acid elevations in mice. METHODS: Hyperuricemia in mice was induced by
      intraperitoneally administering uric acid (250 mg/ kg). Concentrations of uric
      acid in serum were determined using the uric acid enzyme method. Mice were
      treated with JDXZD for 4 days before uric acid was administered. RESULTS: After
      intraperitoneal injection of uric acid, serum uric acid concentrations in mice
      significantly increased. However, the levels of uric acid in groups pretreated
      with 16.25 or 4.06 g/kg of JDXZD were significantly lower than those in the model
      and normal groups. CONCLUSION: Pretreatment with JDXZD slowed increases in serum
      uric acid levels in mice intraperitoneally administered uric acid.

PMID- 24660614
TI  - Antimicrobial effect of sodium houttuyfonate on Staphylococcus epidermidis and
      Candida albicans biofilms.
AB  - OBJECTIVE: To study antimicrobial effect of Sodium houttuyfonate (SH) on
      Staphylococcus epidermidis (SE) and Candida albicans (CA). METHODS: The prepared
      strain broths (OD,o=0.05) containing SE and CA were firstly used to test the
      minimal inhibitory concentrations (MICs) of SH, azithromycin (AZM) and
      fluconazole (FLU) by micro-dilution method. Then the biofilms of SE and CA were
      matured in 96-well plates, and co-cultured with SH, AZM and FLU for 1, 2 and 3
      days to assess the antibiofilm efficacies of the agents with different
      concentrations by crystal violet staining method. At last, the treated biofilms
      of SE and CA by 2x MIC agents were observed by scanning electronic microscope.
      RESULTS: The MICs of SE and CA were 256 and 1024 microg/ml, respectively. After
      the 1st, 2nd and 3rd day of medications, the suppressions of biofilm were about
      60% (P < 0.01), 76% (P = 0.000) and 75% (P = 0.000) by 2 x MIC SH, the
      suppressions of biofilm were about 90% (P = 0.000), 88% (P = 0.000) and 90% (P =
      0.000) by 2 x MIC SH, which could be testified by scanning electron microscope
      results. However, the inhibitions of biofilm attachment had no significant
      difference for SE by SH and azithromycin and CA by SH and fluconazole.
      CONCLUSION: SH had widely anti-pathogenic effect on pathogenic biofilm formation
      of either bacteria or fungus, had more influence on enclosed cells of SE and CA
      than the traditional antibiotics, revealing its target might be the extracellular
      polymeric substances, and was more active to inhibit the growth of CA than SE.

PMID- 24660615
TI  - Inhibitive effect on phagocytosis of Candida albicans induced by pretreatment
      with quercetin via actin cytoskeleton interference.
AB  - OBJECTIVE: To investigate the anti-inflammatory effect of pretreatment with
      quercetin on macrophages after Candida albicans infection. METHODS: RAW 264.7
      macrophages were used as a target cell line. Cell viability after treatment with
      quercetin at different time points was detected by Carboxyfluorescein diacetate,
      succinimidyl ester. Phagocytic function of macrophages was determined by a
      fluorometric assay. Cytokine tumor necrosis factor alpha (TNF-alpha) production
      was measured by enzyme-linked immunosorbent assay. F-actin cytoskeleton of L929
      cells was stained by Alexa Fluor 488-phalloidin. RESULTS: Pretreatment with
      quercetin decreased cell viability only at the highest concentration of 37
      microg/mL 2, 24, and 48 h after the treatment. The phagocytic efficiency of
      macrophages pretreated with quercetin was significantly decreased in a time- and
      dose-dependent manner. F-actin labeling showed that the actin cytoskeleton of the
      cells started to break down 2 h after treatment. Moreover, it notably inhibited
      cytokine TNF-alpha production after Candida albicans infection. CONCLUSION:
      Pretreatment with quercetin induced an anti-inflammatory effect against Candida
      albicans infection in macrophages.

PMID- 24660616
TI  - Synergistic antibacterial effect of honey and Herba Ocimi Basilici against some
      bacterial pathogens.
AB  - OBJECTIVE: To evaluate the antibacterial activity of the combination of different
      honey brands and methanolic fraction of Herba Ocimi Basilici using agar well
      diffusion assay. METHODS: The antibacterial activity was determined against
      thirteen pathogenic bacterial clinical isolates including six gram negative
      (Klebsiella pneumonia, Pseudomonas aeroginosa, Escherichia coli, Salmonella
      typhi, Salmonella typhimirium, Xanthomonas campestris) and six gram positive
      strains (Enterococcus faecalis faecalis, Bacillus subtilis, Staphylococcus
      aureus, Clostridium perfringens type C, Clostridium perfringens type D,
      Clostridium chauvoei). Agar well diffusion method was used while zones of
      inhibition were measured with vernier scale. RESULTS: At higher concentration,
      all the honey brands showed good to significant activity. The highest activity
      was observed for Hamdard brand honey (27.60 +/- 0.40) against Enterococcus
      faecalis. CONCLUSION: These results revealed that combinations of plant extracts
      of Herba Ocimi Basilici with honey can be used for the development of potent and
      novel antibacterial agents.

PMID- 24660617
TI  - Parsley: a review of ethnopharmacology, phytochemistry and biological activities.
AB  - OBJECTIVE: To summarize comprehensive information concerning ethnomedicinal uses,
      phytochemistry, and pharmacological activities of parsley. METHODS: Databases
      including PubMed, Scopus, Google Scholar, and Web of Science were searched for
      studies focusing on the ethnomedicinal use, phytochemical compounds and
      biological and pharmacological activities of parsley. Data were collected from
      1966 to 2013. The search terms were: "Parsley" or "Petroselinum crispum" or
      "Petroselinum hortence". RESULTS: Parsley has been used as carminative, gastro
      tonic, diuretic, antiseptic of urinary tract, anti-urolithiasis, anti-dote and
      anti-inflammatory and for the treatment of amenorrhea, dysmenorrhea,
      gastrointestinal disorder, hypertension, cardiac disease, urinary disease,
      otitis, sniffle, diabetes and also various dermal disease in traditional and
      folklore medicines. Phenolic compounds and flavonoids particularly apigenin,
      apiin and 6"-Acetylapiin; essential oil mainly myristicin and apiol; and also
      coumarins are the active compounds identified in Petroselinum crispum. Wide range
      of pharmacological activity including antioxidant, hepatoprotective, brain
      protective, anti-diabetic, analgesic, spasmolytic, immunosuppressant, anti
      platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic,
      hypotensive, antibacterial and antifungal activities have been exhibited for this
      plant in modern medicine. CONCLUSION: It is expectant that this study resulted in
      improvement the tendencies toward Petroselinum crispum as a useful and important
      medicinal plant with wide range of proven medicinal activity.

PMID- 24660618
TI  - Postmarketing studies on safety of Dengfeng shenmai injection.
AB  - OBJECTIVE: To systematically research the postmarketing safety of Dengfeng
      shenmai injection, identify potential risk factors, and ensure its clinical
      safety. METHODS: We investigated a comprehensive series of studies on the
      production process, quality standards, pharmacology, postmarketing clinical
      studies, and safety evaluation of Shenmai injection, including literature
      analysis of adverse drug reaction (ADR) case analysis and systematic review. Data
      from the hospital information system (HIS) and spontaneous reporting system (SRS)
      were also analyzed. RESULTS: The approximate dosage leading to death in dogs is
      45.0-67.5 g raw drug/kg and the toxic reactions are restlessness, skin
      irritation, salivation, and vomiting. The results of chronic toxicity tests in
      mice and dogs, and the other tests such as 6-month toxicity, drug safety, genetic
      toxicity, and reproductive toxicity of rats and dogs, were positive or qualified.
      Patient ADR history and ADR family history were closely associated with itching
      based on the data analysis from SRS. There was no damage to renal function from
      Shenmai injection use at a dosage and a treatment course outside the recommended
      dosage and treatment course as specified based on data analysis from HIS. The
      most common ADR from Shenmai injection are difficulty breathing, facial flushing,
      nausea, vomiting, chest tightness, skin itching, rash, and back pain. CONCLUSION:
      This study includes complete information on Shenmai injection ADR incidence rate.
      We found that Shenmai injection is safe and this study can provide clinical,
      research, and production institutions with an objective, reliable, and scientific
      basis for use of Shenmai injection.

PMID- 24660619
TI  - Papers published from 1995 to 2012 by six Traditional Chinese Medicine
      universities in China: a bibliometric analysis based on science citation index.
AB  - OBJECTIVE: The quality and quantity of published research papers are important in
      both scientific and technology fields. Although there are several bibliometric
      studies based on citation analysis, very few have focused on research related to
      Traditional Chinese Medicine in China. METHODS: The bibliometric method used in
      this study included the following focuses: publication outputs for each year,
      paper type, language of publication, distribution of internationally
      collaborative countries, sources of funding, authorization number, distribution
      of institutes regarding collaborative publications, research fields, distribution
      of outputs in journals, citation, data, and h-index. RESULTS: A total of 3809
      papers published from 1995 to 2012 were extracted from the science citation index
      (SCI). The cumulative number of papers from all six universities is constantly
      increasing. The United States attained the dominant position regarding
      complementary and alternative medicine research. The Chinese Academy of Sciences
      was the greatest participator in collaborative efforts. Research field analysis
      showed that the research mainly focused on pharmacology pharmacy, chemistry,
      integrative complementary medicine, plant sciences, and biochemistry molecular
      biology. The Shanghai University of Chinese Medicine had the most citations.
      CONCLUSION: In recent years, in terms of SCI papers, the six Traditional Chinese
      Medicine universities studied here have made great advances in scientific
      research.

PMID- 24660620
TI  - [Metagenomics in studying gastrointestinal tract microorganism].
AB  - Animal gastrointestinal tract contains a complex community of microbes, whose
      composition ultimately reflects the co-evolution of microorganisms with their
      animal host. The gut microbial community of humans and animals has received
      significant attention from researchers because of its association with health and
      disease. The application of metagenomics technology enables researchers to study
      not only the microbial composition but also the function of microbes in the
      gastrointestinal tract. In this paper, combined with our own findings, we
      summarized advances in studying gastrointestinal tract microorganism with
      metagenomics and the bioinformatics technology.

PMID- 24660621
TI  - [Biosafety issues and public concerns on recombinant influenza viruses generated
      in the laboratories].
AB  - Understanding inter-species transmission of influenza viruses is an important
      research topic. Scientists try to identify and evaluate the functional factors
      determining the host range of influenza viruses by generating the recombinant
      viruses through reverse genetics in laboratories, which reveals the viruses'
      molecular mechanisms of infection and transmission in different species.
      Therefore, the reverse genetic method is a very important tool for further
      understanding the biology of influenza viruses and will provide the insight for
      the prevention and treatment of infections and transmission. However, these
      recombinant influenza viruses generated in laboratories will become the potential
      threat to the public health and the environment. In this paper, we discussed the
      biological safety issues of recombinant influenza viruses and suggested we should
      set up protocols for risk management on research activities related to
      recombinant highly pathogenic influenza viruses.

PMID- 24660622
TI  - [Cloning and expression pattern of erk2 gene in Inner Mongolia Cashmere goat].
AB  - The study aims at cloning the CDS fragment of erk2 gene cDNA in Inner Mongolia
      Cashmere Goat and analyzing its tissue-specific expression, erk2 gene cDNA was
      cloned by RT-PCR. The nucleotide sequence was analyzed by Blast and amino acid
      sequence was analyzed by online softwares SMART and Psite. The tissue-specific
      expression pattern of erk2 was analyzed by quantitative RT-PCR. The expression of
      erk2 in testis of goat was detected by Immunohistochemistry. The cloned erk2 gene
      cDNA (GenBank Accession No. JX569765) was 1 083 bp in length, including a
      complete ORF encoding 360 amino acids residues. The amino acid sequence shares
      100% identity with the Bos Taurus ERK2 (Bos Taurus BC133588.1). Analysis by SMART
      suggests that the encoded protein contained a "TEY" structure and an S-TKc domain
      possessing serine/threonine kinase catalytic activity. Analysis with Psite
      indicates one cAMP-/cGMP-dependent protein kinase phosphorylation site, 3 protein
      kinase C phosphorylation sites, 5 casein kinase II phosphorylation sites, 2
      protein kinases ATP-binding region signatures and one serine/threonine protein
      kinases active-site signature in this protein. Analysis by Psort (k-NN
      prediction) suggestes that this protein most probably is localized in cytoplasm.
      The results of quantitative RT-PCR show that the expression of erk2 mRNA was
      higher in heart, skin and breast, whereas lower in spleen and kidney. ERK2
      protein was detected in testis by immunohistochemistry.

PMID- 24660623
TI  - [Enhanced thermostability of Rhizopus chinensis lipase by error-prone PCR].
AB  - Directed evolution was conducted to improve the thermostability of lipase from
      Rhizopus chinensis CCTCC M201021. Mutations were introduced by two rounds of
      error-prone PCR and mutant lipase was selected by fast-blue RR top agar
      screening. Two positive variants were selected in the first-round and four in the
      second-round screening process. Ep2-4 was proved as the most thermostable lipase
      and its DNA sequencing revealed three amino acid substitutions: A129S, P168L and
      V329A. Compared with the parent, its half-life at 60 degrees C was 5.4- times
      longer and T50 was 7.8 degrees higher. Purified lipase of Ep2-4 was characterized
      and the result shows that its thermostability improved without compromising
      enzyme activity. According to the mimicked protein structure, mutation A129S
      formed a hydrogen bond with Gln133 and improved the thermostability by increasing
      the hydrophilicity and polarity of protein; mutation P168L by forming a
      hydrophobic bond with the nearby Leu164.

PMID- 24660624
TI  - Activation of anti-HBV immune activity by DNA vaccine via electroporation using
      heat shock proteins as adjuvant.
AB  - Although DNA vaccination is now a promising strategy against hepatitis B virus
      (HBV) infection, this approach has relatively modest antiviral effect, indicating
      that immunosuppressive mechanisms may occur in the long-term established
      infection. In this study, we studied the immunogenicity and anti-HBV efficiency
      of a combination of HBV surface (HBsAg) and core (HBcAg) DNA vaccine, enhanced by
      heat shock protein (HSP) gp96 or HSP70 and mediated by in vivo electroporation.
      Immunization with gp96 adjuvanted HBsAg/HBcAg DNA formulation induced potent T
      cell and antibody immunity against HBsAg and HBcAg. Notably, treatment with gp96
      or HSP70 as adjuvant resulted in reduction of Treg populations by around 20%.
      Moreover, compared with nonimmunized control mice, immunization with gp96 or
      HSP70 adjuvanted DNA vaccine dramatically decreased serum HBsAg and viral DNA
      levels, and HBcAg expression in liver. These results may therefore provide an
      effective strategy for designing gp96-based DNA vaccine for immunotherapy of
      chronic HBV infection.

PMID- 24660625
TI  - [Expression of herpes simplex virus type 2 latency associated transcript ORF1 and
      its anti-apoptotic function].
AB  - To study the expression of herpes simplex virus type 2 latency-associated
      transcript (LAT) open reading frame 1 (ORF1) and its anti-apoptosis function
      induced by actinomycin D in Vero cells. The recombinant plasmid pEGFP-ORF1 was
      constructed and transfected into Vero cells, and the expression of ORF1 was
      identified by RT-PCR. The changes of Vero cells morphology induced by actinomycin
      D were observed by fluorescence microscopy, Hochest33258 fluorescence staining.
      Cells viability was evaluated by MTT assay and cells apoptosis rate was detected
      by flow cytometry. Double digestion and sequencing confirmed the pEGFP-ORF1 was
      constructed successfully, RT-PCR showed that the target gene was highly expressed
      in Vero cells. Hochest33258 staining reaveals that Vero cells transfected with
      pEGFP-ORF1 and induced apoptosis by actinomycin D had no changes in morphology.
      MTT assay showed that the viabilities of Vero cells transfected with recombinant
      plasmid pEGFP-ORF1 and induced apoptosis by actinomycin D has no statistically
      significant difference compared with the untreated normal control group (P >
      0.05), but remarkable higher than Vero cells transfected with empty plasmid pEGFP
      C2 and induced apoptosis by actinomycin D, the difference was statistically
      significant (P < 0.05). Flow cytometry assay shows that the cells apoptosis rate
      had no significant difference between pEGFP-ORF1 group and the normal group, but
      the cells apoptosis rate ofpEGFP-ORF1 was lower than the pEGFP-C2 group. HSV-2
      LAT ORF1 gene can be expressed in Vero cells and can protect Vero cells from
      apoptosis induced by actinomycin D.

PMID- 24660626
TI  - [Construction of an engineered M1GS-HCV/C141 ribozyme and determination of its
      antiviral activity in vitro].
AB  - Hepatitis C virus (HCV), one of the major pathogens of viral hepatitis, causes
      significant hazards in humans. Interferon treatment in combination with ribavirin
      is used as the first line clinical treatment for HCV infection. However, good
      response to this treatment has only been observed in few patients and repeated
      recurrence has also been reported frequently. Therefore, new antiviral agents and
      therapies are in urgent demand. Here, we report a newly constructed Escherichia
      coli RNase P based M1GS ribozyme that can specifically and efficiently target the
      core gene of HCV. The guide sequence (GS) of this M1IGS was designed according to
      the sequence of the core coding region of HCV genome. The GS was then covalently
      linked to the 3' terminus of M1 RNA, the catalytic subunit of RNase P from
      Escherichia coli. The specification of this sequence-specific ribozyme, M1GS, was
      then examined using an in vitro cleavage assay. The cytotoxicity and its activity
      in inhibition of HCV gene expression and viral proliferation were further studied
      in vivo. Our results show that the reconstructed M1GS ribozyme displayed obvious
      catalytic activity in cleaving target mRNAs fragment in vitro. Notable reduction
      in the expression of HCV core protein and a 1 000-fold reduction in viral growth
      were also observed in cultured HCV infected Huh7.5.1 cells expressing the
      functional M1GS ribozyme. This study demonstrated a direct evidence for the
      antiviral activity of the customized M1GS-HCV/C141 ribozyme, and thus provided a
      promising new strategy for clinical treatment of HCV infection.

PMID- 24660627
TI  - [Epithelium constitution for esophageal tissue engineering using electrospinning
      technology].
AB  - The basement membrane (BM) is crucial in regulating the physical and biological
      activities of esophageal epithelial cells which attach to the underlying BM. In
      order to simulate the natural construction of BM, we prepared the fibrous
      scaffolds using biodegradable polylactide (PLA) and silk fibroin (SF) as the
      materials via electrospinning technology. BM's proteins containing collagen (IV),
      laminin, entactin and proteoglycan were extracted from porcine esophagus and
      coated on the eletrospun fibers. Morphology, mechanical strength,
      biodegradability and cytocompatibility of the coated and uncoated scaffolds were
      tested and evaluated using scanning electron micrography, mechanical test system,
      immunofluorescence assay and western blotting with CK14 as the primary antibody.
      The fibrous scaffold PLA or PLA/SF, generated from the present protocol had good
      formation and mechanical and biodegradable properties. After coating with BM's
      proteins, the scaffold could enhance the growth and differentiation of esophageal
      epithelial cells, which would contribute to remodel and regenerate the tissue
      engineered epithelium and further contribute to engineer the whole esophagus in
      future.

PMID- 24660628
TI  - [Stable and efficient expression of hepatitis B virus S antigen and preS1 epitope
      fusion protein (S/preS1) in CHO cells].
AB  - Hepatitis B surface antigen (HBsAg) carrying preS sequences could be an ideal
      candidate for a new hepatitis B virus (HBV) vaccine with higher efficacy. Here we
      report the success in achieving efficient and stable expression of hepatitis B
      virus S antigen and preS1 epitope fusion protein (S/preS1) in CHO cells. The
      HMRCHEF53u/Neo-S/preS1 expression vector carrying S/preS1 gene was constructed
      and transfected into CHO-S cells. A stable and high-expression CHO cell line,
      named 10G6, was selected by ELISA and limiting dilution analysis. Western
      blotting analysis showed S/preS1 expressed from 10G6 cells possessed both S and
      preS1 antigenicity. 10G6 cells displayed characters of favorable growth and
      stable S/preS1 expression in repeated batch cultures as evaluated by viable cell
      density, viability and S/preS1 concentration. And cultivation of 10G6 cells in
      fed-batch mode resulted in S/preS1 production at 17-20 mg/L with viable cell
      density at 7 x 10(6)-10 x 10(6) cells/mL.

PMID- 24660629
TI  - [Angiogenic activity of alginate-graft-PEI/pVEGF complexes in vivo].
AB  - To study the angiogenic activity of amphoteric brush-type copolymer complex of
      alginate-graft-PEI/pVEGF (Alg-g-PEI/pVEGF) in vivo, we evaluated the toxicity of
      Alg-g-PEI/pVEGF complexes to rMSCs and zebra fish first. Then, we used gel
      retardation assay to investigate the protection of complex to pDNA against DNase
      I, serum and heparin. For in vivo study, we evaluated the angiogenic activity of
      Alg-g-PEI/pVEGF complexes by using CAM and zebra fish as animal models, PEI
      25K/pVEGF and saline as positive and negative controls. Our results show that Alg
      g-PEI protected pVEGF from enzymolysis and displacement of heparin in some
      degree, and its complexes with pVEGF were less toxic to rMSCs and zebra fish. Alg
      g-PEI/pVEGF complexes induced significant angiogenesis, which was dosage
      dependent. In CAM, when the dosage of pVEGF was 2.4 microg/CAM, Alg-g-PEI group
      achieved the maximum of angiogenesis, and the area ratio of vessel to the total
      surface was 44.04%, which is higher than PEI 25K group (35.90%) and saline group
      (24.03%) (**P < 0.01). In zebra fish, the angiogenesis increased with the
      increase of N/P ratios of Alg-g-PEI/pVEGF complexes in our studied range; when
      N/P ratio was 110, the optimal angiogenesis was obtained with vessel length of
      1.11 mm and area of 1.70 x 10(3) pixels, which is higher than saline group (0.69
      mm and 0.94 x 10(3) pixels) (**P < 0.01) and PEI 25k group (0.82 mm and 1.11 x
      10(3) pixels) (**P < 0.01). Our results demonstratethat Alg-g-PEI/pVEGF
      significantly induces angiogenesis in CAM and zebra fish, and has a great
      potential in therapeutic angiogenesis.

PMID- 24660630
TI  - [A method to determine the structure of the complex of enzyme and its substrate
      using 6-phosphate-beta-glucosidase at low temperature].
AB  - To capture a state of the enzyme in complex with an intact substrate, we
      developed and adopted a novel freezing method in crystal preparation procedure.
      Neither the elimination of the catalytically indispensable ligands, nor mutation
      or modification of the active site is required. At -20 degrees C, we soaked the
      crystal of 6-phosphate-beta-glucosidase (Bg1A) in the liquor containing p
      nitrophenyl-beta-D-glucopyranoside-6-phosphate (pNPbetaG6P). The diffraction data
      at 2 A resolution was collected and an intact and unambiguous electron density
      map of pNPbetaG6P was obtained. These results provide an effective method for the
      research of cryoenzymology and the intermediate state of enzyme-substrate complex
      in the future.

PMID- 24660631
TI  - [Effects of Ca2+ on salicylic-acid induced biosynthesis of salvianolic acid B in
      young seedlings of Salvia miltiorrhiza Bunge].
AB  - In order to study the effects of Ca2+ in the biosynthesis of salvianolic acid B
      (Sal B) induced by salicylic acid (SA) in the young seedlings of Salvia
      miltiorrhiza, we used confocal laser scanning microscopy and high performance
      liquid chromatography to measure the change of relative fluorescence intensity of
      Ca2+ and the contents of Sal B induced by SA before and after the application of
      extracellular calcium channel inhibitors (VP and LaCl3), intracellular calcium
      channel inhibitor (LiCl), as well as intracellular calmodulin antagonist (TFP).
      SA could induce the calcium burst, and the Ca2+ peak could last to 2-3 min in the
      guard cells of S. miltiorrhiza, which prompted the biosynthesis of Sal B after
      the Ca2+ burst. Both Vp or LaCl3, and LiCl or TFP could inhibit the burst of Ca2+
      and the biosynthesis of Sal B. The above results demonstrated that Ca2+ from the
      extracellular and the intracellular calcium store regulate the biosynthesis of
      Sal B elicited by salicylic acid in S. miltiorrhiz young seedlings.

PMID- 24660632
TI  - [Deletion of marker gene in transgenic goat by Cre/LoxP system].
AB  - In producing transgenic livestock, selectable marker genes (SMGs) are usually
      used to screen transgenic cells from numerous normal cells. That results in SMGs
      integrating into the genome and transmitting to offspring. In fact, SMGs could
      dramatically affect gene regulation at integration sites and also make the safety
      evaluation of transgenic animals complicated. In order to determine the deletion
      time and methods in the process of producing transgenic goats, the feasibility of
      deleting SMGs was explored by Cre/LoxP before or after somatic cell cloning. In
      addition, we compared the efficiency of protein transduction with plasmids co
      transduction. We could delete 43.9% SMGs after screening out the transgenic cell
      clones, but these cells could not be applied to somatic cells cloning because of
      serious aging after two gene modifications. The SMG-free cells suitable for
      nuclear transfer were accessible by using the cells of transgenic goats, but this
      approach was more time consuming. Finally, we found that the Cre plasmid could
      delete SMGs with an efficiency of 7.81%, but about 30% in SMG-free cells had
      sequences of Cre plasmid. Compared with Cre plasmid, the integration of new
      exogenous gene could be avoided by TAT-CRE protein transduction, and the deletion
      rate of TAT-CRE transduction was between 43.9 and 72.8%. Therefore, TAT-Cre
      transduction could be an effective method for deleting selectable marker genes.

PMID- 24660633
TI  - [Effect of co-expression of nicotinic acid phosphoribosyl transferase and
      pyruvate carboxylase on succinic acid production in Escherichia coli BA002].
AB  - Escherichia coli BA002, in which the ldhA and pflB genes are deleted, cannot
      utilize glucose anaerobically due to the inability to regenerate NAD+. To restore
      glucose utilization, overexpression of nicotinic acid phosphoribosyltransferase
      (NAPRTase) encoded by the pncB gene, a rate-limiting enzyme of NAD(H) synthesis
      pathway, resulted in a significant increase in cell mass and succinate production
      under anaerobic conditions. However, a high concentration of pyruvate was
      accumulated. Thus, co-expression of NAPRTase and the heterologous pyruvate
      carboxylase (PYC) of Lactococcus lactis subsp. cremoris NZ9000 in recombinant E.
      coli BA016 was investigated. Results in 3 L fermentor showed that OD600 is 4.64
      and BA016 consumed 35.00 g/L glucose and produced 25.09 g/L succinate after 112 h
      under anaerobic conditions. Overexpression of pncB and pyc in BA016, the
      accumulation of pyruvic acid was further decreased, and the formation of succinic
      acid was further increased.

PMID- 24660634
TI  - [Effects of pH and oxygen supply on production of 2,3-butanediol from biodiesel
      derived glycerol by Bacillus amyloliquefaciens].
AB  - Bacillus amyloliquefaciens B10-127 was used to produce 2,3-butanediol (2,3-BD)
      from residual glycerol obtained from biodiesel synthesis. Important variables for
      2,3-BD fermentation, pH and dissolved oxygen, were studied. When pH was
      maintained constant, the yield of 2,3-BD was inhibited. The highest 2,3-BD yields
      were achieved by fermentation without any pH control with an optimized initial pH
      6.5. Batch fermentative production of 2,3-BD by B. amyloliquefaciens was
      investigated using various oxygen supply methods by changing agitation speed.
      Based on the analysis of three kinetic parameters including specific cell growth
      rate (micro), specific glucose consumption rate (q(s)) and specific 2,3-BD
      formation rate (q(p)), a three-stage agitation speed control strategy was
      proposed, aimed at achieving high concentration, high yield and high productivity
      of 2,3-BD. Maximum concentration of 2,3-BD reached 38.1 g/L, with the
      productivity of 1.06 g/(L x h), which were 14.8% and 63.1% over the best results
      from constant agitation speeds. In a pulse fed-batch fermentation, 2,3-BD
      concentration and productivity were significantly improved to 71.2 g/L and 0.99
      g/(L x h), respectively. To our knowledge, these results were the highest for 2,3
      BD production from biodiesel-derived glycerol.

PMID- 24660635
TI  - [Effects of nitrogen sources on growth density, lipid yield and eicosapentaenoic
      acid of Nannochloropsis oculata].
AB  - Nitrogen source is one of the important factors that affect the microalgae growth
      and lipid accumulation. We studied the effects of various nitrogen sources (i.e.
      NaNO3, CO(NH2)2, NH4Cl and CH3COONH4) and amount on the growth density, lipid
      yield, and eicosapentaenoic acid (EPA) content of Nannochloropsis oculata by
      single factor experimental method. The results show that N. oculata preferred
      NH4+ as nitrogen source rather than NO3- and CO(NH2)2. NH4+ could promote the
      growth and lipid accumulation of N. oculata. With the increase of nitrogen
      concentration, the biomass and the content of polyunsaturated fatty acid (PUFA)
      increased, but the content of lipid decreased. CH3COONH4 was the most suitable
      for growth, accumulation of lipid and EPA of N. oculata among the four
      investigated nitrogen sources. The optimal concentration was 5.29 mmol/L.

PMID- 24660636
TI  - [Identification of Bacillus subtilis THY-7 and high titer optimization for the
      blend-biosurfactant of lipopeptide and glycolipid].
AB  - Biosurfactants (BSs) are highlighted owing to their multiple advantages in
      diverse applications. To screen a superior strain that producing a blend
      biosurfactant of lipopeptide and glycolipid, the hemolytic activity assay on
      blood agar plates, the modified oil-red spreading test and MALDI-TOF Mass
      Spectrometry identification of the purified products was carried out. Bacillus
      subtilis THY-7 was selected and its principal products were surfactin and
      dirhamnolipid. The medium component and culture conditions of THY-7 were
      optimized by both single factor and orthogonal experiments. After 48 h optimal
      batch culture in flask, the cell density (OD600) was 37.0 and the product titer
      was 2.4 g/L, which was 3.4 folds and 3.1 folds of that under original condition,
      respectively. A fed-batch culture in a 5 L fermentor was further performed
      coupling with in situ recovery of foam, in which the titer of blend-BS increased
      to 4.5 g/L at 25 h. Quantification by HPLC and anthrone colorimetry revealed that
      surfactin and dirhamnolipid accounted for 74% and 22% of the blend-BS,
      respectively.

PMID- 24660637
TI  - [Succinic acid production with Escherichia coli AFP111 recovered from
      fermentation].
AB  - During the anaerobic fermentation by Escherichia coli AFP111 for succinic acid
      production, the viable cell concentration and productivity were decreased with
      the raising of succinic acid concentration. In order to restore cellular succinic
      acid productivity and prolong fermentation time, we collected strains and
      refreshed medium for repetitive succinic acid production. However, productivity
      is lower than that in the anaerobic fermentation before reusing strains. To
      enhance the productivity, strains were aerobically cultivated for 3 h in pure
      water before anaerobic fermentation. The activities of key enzymes were enhanced
      for better performance in producing succinic acid at anaerobic stage. After three
      rounds of repetitive fermentations, succinic acid concentration and yield reached
      to 56.50 g/L and 90% respectively. The succinic acid productivity was 0.81 g/(L x
      h), which was 13% higher than the repetitive fermentations without aerobic
      activation of the strains.

PMID- 24660638
TI  - [Effect of cell culture conditions on antibody heterogeneity].
AB  - With the advantage of clear target and little side effect, antibody drug has
      attracted widely attention of worldwide pharmaceutical companies. However, large
      scale mammalian cell culture and antibody quality analysis are the bottlenecks of
      antibody drug industrialization in China. Especially due to the significant
      effect of cell culture conditions on antibody heterogeneity. Therefore, it is
      extremely urgent to optimize cell culture conditions to favor the demands of
      antibody drug development. This review summarized the most recent advances in the
      effect of cell culture conditions on antibody quality, followed by addressing the
      key issues that might be strategically important for domestic antibody drug
      development.

PMID- 24660639
TI  - New CRANIO cover information.

PMID- 24660640
TI  - The role of dentistry in the field of sleep medicine...are we respecting the
      physiology?

PMID- 24660641
TI  - Who is in control--the teeth or the temporomandibular joints?

PMID- 24660642
TI  - Clinician accuracy when subjectively interpreting articulating paper markings.
AB  - AIMS: The aim of this study was to determine whether Subjective Interpretation of
      paper markings is a reliable method for identifying the relative occlusal force
      content of tooth contacts. METHODOLOGY: 295 clinicians selected the "Most
      Forceful" and "Least Forceful" occlusal contacts in six occlusal-view photographs
      of articulating paper marks that were later compared against computerized
      occlusal analysis relative occlusal force measurements of the same tooth
      contacts. Means and standard deviations were calculated by years in clinical
      practice and by number of occlusion courses taken. A Chi-square analysis was also
      performed. RESULTS: The mean correct for 295 participant dentists was 1.53 (+/-
      1.234). There were no significant differences found for years in practice
      (P>0.16) or number of occlusion courses taken (P>0.75). The Chi-square analysis
      showed a sensitivity of 12.6%, a specificity of 12.4%, a positive predictive
      value of 12.58%, and a negative predictive value of 12.42%. Chance was calculated
      at 12.5% correct. CONCLUSIONS: Subjective Interpretation is an ineffective
      clinical method for determining the relative occlusal force content of tooth
      contacts. The reported low scores obtained from a large group of participant
      dentists suggest clinicians are unable to reliably differentiate high and low
      occlusal force from looking at articulating paper marks. This longstanding method
      of visually observing articulating paper marks for occlusal contact force content
      should be replaced with a measurement-based, objective method.

PMID- 24660643
TI  - Comprehensive treatment of temporomandibular joint disorders.
AB  - AIMS: Changing lifestyles, decreasing physical activity, which is increasing the
      number of degenerative joint diseases of various etiology, and certain dental
      procedures are increasing the number of patients complaining of pain in their
      temporomandibular joints. The aim of the study was to assess the benefits of
      comprehensive physiotherapy sessions in order to decrease the number of
      temporomandibular joint problems, thereby improving the patient's quality of
      life. METHODOLOGY: An examination by a dentist determined each patient's
      treatment plan, which consisted of a medical exam, physical therapy and
      education. Each form of treatment was applied 10 times at intervals of 7-14 days.
      The main goal of the therapeutic physical education was to redress the muscle
      imbalance in the mandibular joint. This was achieved by restoring balance between
      the masticatory muscles, along with releasing the spastic shrouds found in the
      masticatory muscles. The aim of education was to teach the patient exercises
      focused on the temporomandibular joint and masticatory muscles. The intensity of
      the exercises and their composition were individually adjusted and adapted to
      their current state. Physical therapy consisted of the application of pulsed
      magnetic therapy, laser therapy, and non-invasive positive thermotherapy.
      RESULTS: The above procedure was conducted on a therapeutic group of 24 patients
      (3 men and 20 women). In the course of therapy, there were no complications, and
      all patients adhered to the prescribed regime. None reported any side effects.
      The mean treatment duration was 123 +/- 66 days. The outcome of the therapy was
      evaluated as described in the methodology, the degree of pain affecting the
      joint, and the opening ability of the mouth. In both parameters, there was a
      significant decline in patient pain. CONCLUSIONS: In a study devoted to tactics
      of rehabilitation treatment for temporomandibular joint disorders, the need for
      comprehensive long-term therapy, involving education, and learning proper chewing
      habits was made apparent for recovery and pain reduction. A priority in physical
      therapy, and combinations of pulsed magnetic therapy and hyperthermia-positive
      peloids, are also beneficial.

PMID- 24660644
TI  - Stomatognathic system involvement in rheumatoid arthritis patients.
AB  - AIMS: Temporomandibular joint (TMJ) and stomatognathic system involvement are
      usually observed during the course of rheumatoid arthritis. METHODOLOGY: This
      article presents the findings during examination of 190 TMJs from rheumatoid
      arthritis (RA) patients, and 44 TMJs from controls without RA, including a
      description of signs and symptoms related to the stomatognathic system,
      radiological findings in hands-, and TMJ, erythrocyte sedimentation rate (ESR)
      values, and scores obtained in the Disease Activity Score (Das 28) and the Health
      Assessment Questionnaire (HAQ). RESULTS: The sample included 57.89% TMJs
      associated with spontaneous pain, 87.89% with signs of destruction in
      radiological images, and 58.94% with 20 teeth or less. Restricted mouth opening
      was detected in 42.1% of RA patients, from which 71% had blocked opening;
      headache was present in 58%, and pain in the masticatory muscles was found in
      57%. TMJ erosions had a significant association with Larsen scores (r=0.62), but
      not with the Das 28, HAQ, and ESR values. CONCLUSIONS: The early evaluation of
      this joint and the collaborative work of odontologists and rheumatologists are
      both necessary for a better management of TMJ pathologies.

PMID- 24660645
TI  - Low-level laser therapy for management of TMJ osteoarthritis.
AB  - AIMS: This study investigated the efficacy of low-level laser therapy (LLLT) for
      the management of temporomandibular joint (TMJ) osteoarthritis. METHODOLOGY: In a
      double-blind clinical trial, 20 patients with TMJ osteoarthritis were randomly
      divided into laser and placebo groups. The patients in the laser group received
      irradiation from an 810 nm low-level laser (Peak power 80 W, average power 50 mW,
      1500 Hz, 1 micro s pulse width, 120 seconds, 6 J, 3.4 J/cm(2) per point), which
      was applied on four points around the TMJs and on painful muscles three times a
      week for 4 weeks. In the placebo group, the treatment was the same as that in the
      laser group, but with laser simulation. The patients were evaluated before laser
      therapy (T1), after 6 (T2) and 12 (T3) laser applications and 1 month after the
      last application (T4), and the amount of mouth opening and the pain intensity
      were recorded. RESULTS: No significant differences were found in mouth opening
      either between the study groups or between the different evaluation times in each
      group (P>0.05). There was no significant difference in pain symptoms of the
      masticatory muscles and TMJ between the laser and the placebo groups (P>0.05),
      but some significant within-group improvements were present for Visual Analogue
      Scale (VAS) scores of the body of the masseter and TMJ in both groups.
      CONCLUSIONS: LLLT using the present laser parameters was no more effective than
      the placebo treatment for reducing pain and improving mouth opening in patients
      with TMJ osteoarthritis.

PMID- 24660646
TI  - Jaw clenching effects in relation to two extreme occlusal features: patterns of
      diagnoses in a TMD patient population.
AB  - OBJECTIVE: The aim of this investigation was to compare the pattern of
      temporomandibular disorder (TMD) diagnoses in clenching patients with different
      occlusal features, the null hypothesis being that no between-group differences
      exist. MATERIALS AND METHODS: Two groups of subjects receiving a jaw clenching
      diagnosis and having large overjet or anterior open bite (Group A; N=45, 75.5%
      females, mean age: 38.1 +/- 15.9 years) or normal occlusion (Group B; N=69, 71%
      females, mean age: 34.6 +/- 13.8 years) were recruited among a TMD patient
      population and were given Research Diagnostic Criteria for TMD (RDC/TMD) axis I
      diagnoses, namely, group I muscle disorders, group II disc displacements, and
      group III arthralgia/osteoarthritis/osteoarthrosis. MAJOR FINDINGS: The
      distribution of RDC/TMD single and combined group diagnoses was significantly
      different between the two groups (P<0.05), with Group A subjects showing a higher
      prevalence of multiple diagnoses (60% versus 43.3%), as well as a higher
      prevalence of combined RDC/TMD axis I group II and III diagnoses (37.8% versus
      20.2%). All TMD signs and symptoms were more frequent in the patients with large
      overjet or anterior open bite with respect to the patients with normal occlusion.
      CONCLUSION: In a TMD patient population, jaw clenching may have different
      consequences in subjects with large overjet or anterior open bite with respect to
      subjects featuring normal occlusion.

PMID- 24660647
TI  - Efficacy of red and infrared lasers in treatment of temporomandibular disorders-
      a double-blind, randomized, parallel clinical trial.
AB  - AIM: Low-level laser therapy has still not been well established, and it is
      important to define a standardized protocol for the treatment of
      temporomandibular disorders (TMDs) using low level laser. There is no consensus
      on controlled clinical trials concerning the best option for laser therapy with
      regard to wavelength. The aim of this study was to evaluate the efficacy of red
      and infrared laser therapy in patients with TMD, using a randomized parallel
      group double-blind trial. METHODOLOGY: Each hemiface of 19 subjects was
      randomized to receive intervention, in a total of 116 sensitive points. Pain was
      measured at baseline and time intervals of 24 hours, 30 days, 90 days, and 180
      days after treatment. Irradiation of 4 J/cm2 in the temporomandibular joints and
      8 J/cm(2) in the muscles was used in three sessions. RESULTS: Both treatments had
      statistically significant results (P<0.001); there was statistical difference
      between them at 180 days in favor of the infrared laser (P=0.039). There was
      improvement in 24 hours, which extended up to 180 days in both groups.
      CONCLUSION: Both lasers are effective in the treatment and remission of TMD
      symptoms.

PMID- 24660648
TI  - Comparison of masticatory muscle myofascial pain in patients with and without a
      chief complaint of headache.
AB  - OBJECTIVES: Headaches are a common complaint in temporomandibular disorder (TMD)
      patients. However, few studies have compared the symptom characteristics between
      TMD patients with and without a complaint of headache. The aim of this study was
      to compare subjective symptoms and treatment outcomes between myofascial TMD
      patients who had a chief complaint of headache and those who did not. METHODS:
      One hundred sixty one patients underwent comprehensive examinations and scored
      their pre- and post-treatment symptoms on a form (4 items assessing pain
      intensity and 1 assessing sleeping difficulty). On the basis of the primary
      diagnosis, patients were divided into two groups: myofascial pain with and
      without a chief complaint of headache (MPH and MP). RESULTS: Before treatment,
      patients in the MPH group scored significantly higher with respect to pain
      intensity and level of sleeping difficulty than did patients in the MP group
      (jaw/face pain, P = 0.015; headache, P < 0.001; neck pain, P < 0.001, and
      difficulty in sleeping, P = 0.005; Mann-Whitney U-test). Patients in the two
      groups demonstrated similar treatment outcomes, except for neck pain. CONCLUSION:
      Significant differences in symptom characteristics and outcomes were observed
      between primarily myofascial TMD patients with and without a chief complaint of
      headache.

PMID- 24660649
TI  - Features and management of intracranial mandibular condyle dislocation after
      trauma.
AB  - BACKGROUND: Dislocation of the mandibular condyle into the middle cranial fossa
      is rare in clinics. It often occurs when the mouth is open wide during the
      injury. It causes restriction of mandibular motion, lower facial asymmetry, pain
      in the temporomandibular joint (TMJ), etc. OBJECTIVE: To introduce the features
      of intracranial mandibular condyle dislocation and discuss the management to this
      kind of trauma. MAJOR FINDINGS: In this paper, the authors present two cases,
      describing the diagnosis, surgical management, and 1-year follow-up evaluation.
      The results of the authors' treatment to intracranial mandibular condyle
      dislocation were satisfactory and stable, and no surgical complications were
      detected. CONCLUSION: Advanced imaging studies are mandatory for exact diagnosis
      and successful treatment of intracranial mandibular condyle dislocation, and
      individualized management is recommended.

PMID- 24660650
TI  - The efficacy of a specific stabilization splint.
AB  - BACKGROUND: The use of a Tanner type stabilization splint, fabricated on a leaf
      gauge articulation for the treatment of patients with disc displacement without
      reduction, is lacking in the literature. OBJECTIVES: The purpose of the study is
      to collect non-controlled, therapy-related observations; in other words, to
      demonstrate the efficacy of this appliance for the treatment of patients with
      disc displacement without reduction. METHODS: The study enrolled 55 patients, 5
      men, and 50 women, with the clinical diagnosis disc displacement without
      reduction, 42 with and 13 without limited mouth opening. All patients received a
      splint in the musculoskeletally stable centric relation (CR) position. Mouth
      opening, clinical performance, and the timeframe of splint treatment were
      assessed. RESULTS: For 37 patients with a disc displacement without reduction
      with limited opening, the largest increase in mouth opening (9.5 +/- 5.6 mm)
      occurred in the first week (7.9 +/- 2.5 days). No occlusal adjustment of the
      splint was needed during the treatment sequence. For three patients, treatment
      took up to 3 months (8.1%), for 13 patients, between 3 and 6 months (35.1%), and
      for 17 patients, within a year (45.9%), making a total of 89.1% successfully
      treated patients. Out of 50 patients, 29 had a total resolution of signs and
      symptoms, whereas 21 patients still suffered from solitary temporomandibular
      disorder (TMD) signs. CONCLUSION: A Tanner type stabilization splint, fabricated
      in the musculoskeletally stable CR position, appears to be an effective and
      efficient means for the treatment of patients with disc displacement without
      reduction. Its efficacy makes it eligible to be tested in a randomized controlled
      trial. CLINICAL IMPLICATIONS: The efficacy of this specific splint, fabricated in
      the musculoskeletally stable CR position, makes it a promising tool to treat TMD
      patients with disc displacement without reduction.

PMID- 24660651
TI  - Novel oral detoxification of mercury, cadmium, and lead with thiol-modified
      nanoporous silica.
AB  - We have developed a thiol-modified nanoporous silica material (SH-SAMMS) as an
      oral therapy for the prevention and treatment of heavy metal poisoning. SH-SAMMS
      has been reported to be highly efficient at capturing heavy metals in biological
      fluids and water. Herein, SH-SAMMS was examined for efficacy and safety in both
      in vitro and in vivo animal models for the oral detoxification of heavy metals.
      In simulated gastrointestinal fluids, SH-SAMMS had a very high affinity (Kd) for
      methyl mercury (MeHg(I)), inorganic mercury (Hg(II)), lead (Pb(II)), and cadmium
      (Cd(II)) and was superior to other SAMMS with carboxylic acid or phosphonic acid
      ligands or commercially available metal chelating sorbents. SH-SAMMS also
      effectively removed Hg from biologically digested fish tissue with no effect on
      most nutritional minerals found in fish. SH-SAMMS could hold Hg(II) and MeHg(I)
      tightly inside the nanosize pores, thus preventing bacteria from converting them
      to more absorbable forms. Rats fed a diet containing MeHg(I), Cd(II), and Pb(II)
      and SH-SAMMS for 2 weeks had blood Hg levels significantly lower than rats fed
      the metal-rich diet only. Upon cessation of the metal-rich diet, continued
      administration of SH-SAMMS for 2 weeks facilitated faster and more extensive
      clearance of Hg than in animals not continued on oral SH-SAMMS. Rats receiving SH
      SAMMS also suffered less weight loss as a result of the metal exposure. Retention
      of Hg and Cd in major organs was lowest in rats fed with SH-SAMMS throughout the
      entire four weeks. The reduction of blood Pb by SH-SAMMS was significant. SH
      SAMMS was safe to intestinal epithelium model (Caco-2) and common intestinal
      bacteria (Escherichia coli). Altogether, it has great potential as a new oral
      drug for the treatment of heavy metal poisoning. This new application is enabled
      by the installation of tailored interfacial chemistry upon nontoxic nanoporous
      materials. 

PMID- 24660653
TI  - New York City's efforts to address childhood obesity: what works, lessons
      learned, and plans for the future.

PMID- 24660652
TI  - Towards an animal model of ovarian cancer: cataloging chicken blood proteins
      using combinatorial peptide ligand libraries coupled with shotgun proteomic
      analysis for translational research.
AB  - Epithelial ovarian cancer is the most deadly gynecological cancer around the
      world, with high morbidity in industrialized countries. Early diagnosis is key in
      reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal
      models are still limited for ovarian cancer. This calls for broader omics and
      systems science oriented diagnostics strategies. In this vein, the domestic
      chicken has been used as an ovarian cancer animal model, owing to its high rate
      of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been
      considered a surrogate reservoir from which cancer biomarkers can be identified.
      However, the presence of highly abundant proteins in chicken blood has
      compromised the applicability of proteomics tools to study chicken blood owing to
      a lack of immunodepletion methods. Here, we demonstrate that a combinatorial
      peptide ligand library (CPLL) can efficiently remove highly abundant proteins
      from chicken blood samples, consequently doubling the number of identified
      proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog
      of 264 unique proteins. Functional analyses further suggested that most proteins
      were coagulation and complement factors, blood transport and binding proteins,
      immune- and defense-related proteins, proteases, protease inhibitors, cellular
      enzymes, or cell structure and adhesion proteins. Semiquantitative spectral
      counting analysis identified 10 potential biomarkers from the present chicken
      ovarian cancer model. Additionally, many human homologs of chicken blood proteins
      we have identified have been independently suggested as diagnostic biomarkers for
      ovarian cancer, further triangulating our novel observations reported here. In
      conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer
      model provides a feasible platform for translational research to identify ovarian
      cancer biomarkers and understand ovarian cancer biology. To the best of our
      knowledge, we report here the most comprehensive survey of the chicken blood
      proteome to date.

PMID- 24660654
TI  - Where's the silver? Imaging trace silver coverage on the surface of gold
      nanorods.
AB  - The development of the seeded growth synthesis for gold nanorods provided the
      first simple, convenient wet chemistry route to these nanomaterials. Over the
      past decade, the original silver-assisted seeded growth procedure has been the
      subject of further modifications that have continuously expanded access to
      anisotropic gold nanoparticles; however, the role of silver in formation of gold
      nanorods remains poorly understood. We report the first experimental evidence on
      the position of silver present on gold nanorods using advanced energy dispersive
      X-ray spectroscopy. Our results indicate the deposition of silver ions on the
      surface shows no preference for a specific face or axis. Furthermore, we show
      that the "dog bone" structures developed from gold nanorod solutions show
      preferential deposition of silver atoms on the ends and in the crevices. 

PMID- 24660655
TI  - Independent risk factors for ventilator-associated pneumonia after cardiac
      surgery.
AB  - OBJECTIVE: To investigate the related factors and pathogens of ventilator
      associated pneumonia (VAP) after heart surgery so as to provide evidences for
      clinical prevention and therapy. METHODS: In total 1,688 cases were collected
      from January 2004 to January 2011. Overall 105 patients developed VAP.
      Retrospectively analyzed these patients after heart surgery to determine the
      clinical data, pathogens and treatment measures. RESULTS: The frequency of
      ventilator-associated pneumonia was 6.2% (105/1 688), and mortality was 25.7%
      (27/105), 198 pathogen strains were isolated by bacterial culture, in which Gram
      negative bacteria accounted for 69.2% (137/198), Gram positive bacteria 27.8%
      (55/198), and fungi 3.0% (6/198). The independent risk factors for VAP after
      cardiac surgery were: age >70 (p < .01), emergent surgery (p < .01),
      perioperative blood transfusions (p < 0.01), reintubation (p < .01) and days of
      mechanical ventilation (MV) (p < .01). Median length of stay in the ICU for
      patients who developed VAP or not was, respectively, (24.7 +/- 4.5) days versus
      (3.2 +/- 1.5) days (p < .05), and mortality was, respectively, 25.7% versus 2.9%
      in both populations (p < .05). CONCLUSION: Age >70, emergent surgery,
      perioperative blood transfusions, reintubation and days of MV are the risk
      factors for VAP in patients following cardiac surgery. P. aeruginosa, P.
      klebsiella, S. aureus, and Acinetobacter baumannii were the main pathogens of
      VAP. According to the cause of VAP, active prevention and treatment measures
      should be developed and applied to shorten the time of MV and improve chances of
      survival.

PMID- 24660657
TI  - The role of the circadian clock in animal models of mood disorders.
AB  - An association between circadian clock function and mood regulation is well
      established and has been proposed as a factor in the development of mood
      disorders. Patients with depression or mania suffer disturbed sleep-wake cycles
      and altered rhythms in daily activities. Environmentally disrupted circadian
      rhythms increase the risk of mood disorders in the general population. However,
      proof that a disturbance of circadian rhythms is causally involved in the
      development of psychiatric disorders remains elusive. Using clock gene mutants,
      manipulations of sleep-wake and light-dark cycles, and brain lesions affecting
      clock function, animal models have been developed to investigate whether
      circadian rhythm disruptions alter mood. In this review, selected animal models
      are examined to address the issue of causality between circadian rhythms and
      affective behavior.

PMID- 24660656
TI  - Modern scientific evidence pertaining to criminal investigations in the Chosun
      dynasty era (1392-1897 A.C.E.) in Korea.
AB  - A guidebook detailing the process of forensic investigation was written in 1440
      A.C.E. It outlines the fundamentals and details of each element of criminal
      investigation during the era of the Chosun dynasty in Korea. Because this old
      guidebook was written in terms of personal experience rather than on scientific
      basis, it includes many fallacies from the perspective of modern forensic
      science. However, the book describes methods to form a scientific basis for the
      experiments performed. We demonstrate the modern scientific basis for ancient
      methods to monitor trace amounts of blood and detect lethal arsenic poisoning
      from a postmortem examination as described in this old forensic guidebook. Traces
      of blood and arsenic poisoning were detected according to the respective color
      changes of brownish red, due to the reaction of ferric ions in blood with acetic
      ions of vinegar, and dark blue, due to the reaction of silver with arsenic
      sulfide. 

PMID- 24660658
TI  - Rhythm and mood: relationships between the circadian clock and mood-related
      behavior.
AB  - Mood disorders are multifactorial and heterogeneous diseases caused by the
      interplay of several genetic and environmental factors. In humans, mood disorders
      are often accompanied by abnormalities in the organization of the circadian
      system, which normally synchronizes activities and functions of cells and
      tissues. Studies on animal models suggest that the basic circadian clock
      mechanism, which runs in essentially all cells, is implicated in the modulation
      of biological phenomena regulating affective behaviors. In particular, recent
      findings highlight the importance of the circadian clock mechanisms in
      neurological pathways involved in mood, such as monoaminergic neurotransmission,
      hypothalamus-pituitary-adrenal axis regulation, suprachiasmatic nucleus and
      olfactory bulb activities, and neurogenesis. Defects at the level of both, the
      circadian clock mechanism and system, may contribute to the etiology of mood
      disorders. Modification of the circadian system using chronotherapy appears to be
      an effective treatment for mood disorders. Additionally, understanding the role
      of circadian clock mechanisms, which affect the regulation of different mood
      pathways, will open up the possibility for targeted pharmacological treatments.

PMID- 24660659
TI  - Assignment of primary site in high-grade serous tubal, ovarian and peritoneal
      carcinoma: a proposal.
AB  - The revised FIGO 2013 staging for carcinomas of the ovary, fallopian tube and
      peritoneum has introduced a single system for tumours originating at these sites.
      The system requires pathologists to assign a primary site (ovary, tube or
      peritoneum), but does not provide guidance to aid this assignment. This is
      particularly problematic in cases of advanced-stage (stage II or greater) high
      grade serous carcinoma (HGSC), where there is commonly involvement of two or more
      sites by tumour, and practice among pathologists in determining where a tumour
      has arisen varies widely. This has significant implications for recording of
      tumour incidence and mortality, data collection by cancer registries, and entry
      into clinical trials. We propose guidelines for assigning the primary site of
      HGSC based on careful macroscopic and histological assessment. The use of these
      guidelines, in conjunction with the new FIGO staging system, is intended to act
      as an impetus to promote debate and provide a uniform and consistent approach in
      assigning primary tumour site which will facilitate comparison of data between
      centres. 

PMID- 24660660
TI  - A patent review on the development of human cytochrome P450 inhibitors.
AB  - INTRODUCTION: CYP, a ubiquitous superfamily of enzymes expressed in major organs
      in humans, plays a key role in biosynthesis of steroids and metabolism of
      xenobiotics. Inhibitors of these vital enzymes provide, as tools, the opportunity
      to gain an insight to their role in a myriad of bioactivity and to intervene as
      therapeutics in disease. AREAS COVERED: This article reviews granted patents for
      human CYP inhibitors from the US and European territories within the past decade.
      EXPERT OPINION: Granted patents, albeit mostly embodying evidence from in vitro
      and limited preclinical trials, demonstrate good potential for use in industry
      and the clinic following future human trials. Indeed, only a handful is on the
      market or under clinical evaluation. Diagnostic monoclonal antibodies (mAbs) show
      high specificity for CYP families 1, 2, and 3, while potent inhibitors of CYPs
      17, 19, 24, 26, 3A4 activities, in use with or without other drugs, display
      potential in treating prostate and breast cancers, dermatology, and improved
      retroviral therapy, although some may have challenges in delivery to target
      tissues. The involvement of this superfamily of enzymes in cellular functions, a
      multitude of disease states, and pharmacogenetics make them ideal candidates to
      better understand contemporary human health issues and identification of
      targeted, specific, and potent inhibitors is a useful strategy to employ, toward
      achieving that wider goal.

PMID- 24660662
TI  - The impact of DNA methylation technologies on drug toxicology.
AB  - INTRODUCTION: Drug toxicology is central to drug development. Despite
      improvements in our understanding of molecular and cell biology, high attrition
      rates in drug development continue, speaking to the difficulties of developing
      unequivocal methods to predict the efficacy and safety of drugs. AREAS COVERED:
      In this review, the authors provide a short overview of the 'omics' technologies
      that have been applied to drug toxicology, with an emphasis on a whole-genome DNA
      methylation analysis. Preliminary results from DNA methylation analysis
      technologies that may help in predicting response and efficacy of a drug are
      discussed. EXPERT OPINION: Currently, we cannot fully contextualize the
      application of epigenetics to the field of drug toxicology, as there are still
      many challenges to overcome before DNA methylation-based biomarkers can be
      effectively used in drug development. Comprehensive whole-genome DNA methylation
      methods for a unbiased analysis based on either microarray or next-generation
      sequencing need to be evaluated in drug toxicology in an intensive and systematic
      manner. Additionally, robust analysis systems need to be developed to decode the
      large amounts of data generated by whole-genome DNA methylation analyses as well
      as protocol standardization for reproducibility to develop meaningful databases
      that can be applied to drug toxicology.

PMID- 24660663
TI  - Analysis of regional scale risk of whirling disease in populations of Colorado
      and Rio Grande cutthroat trout using a Bayesian belief network model.
AB  - Introduction and spread of the parasite Myxobolus cerebralis, the causative agent
      of whirling disease, has contributed to the collapse of wild trout populations
      throughout the intermountain west. Of concern is the risk the disease may have on
      conservation and recovery of native cutthroat trout. We employed a Bayesian
      belief network to assess probability of whirling disease in Colorado River and
      Rio Grande cutthroat trout (Oncorhynchus clarkii pleuriticus and Oncorhynchus
      clarkii virginalis, respectively) within their current ranges in the southwest
      United States. Available habitat (as defined by gradient and elevation) for
      intermediate oligochaete worm host, Tubifex tubifex, exerted the greatest
      influence on the likelihood of infection, yet prevalence of stream barriers also
      affected the risk outcome. Management areas that had the highest likelihood of
      infected Colorado River cutthroat trout were in the eastern portion of their
      range, although the probability of infection was highest for populations in the
      southern, San Juan subbasin. Rio Grande cutthroat trout had a relatively low
      likelihood of infection, with populations in the southernmost Pecos management
      area predicted to be at greatest risk. The Bayesian risk assessment model
      predicted the likelihood of whirling disease infection from its principal
      transmission vector, fish movement, and suggested that barriers may be effective
      in reducing risk of exposure to native trout populations. Data gaps, especially
      with regard to location of spawning, highlighted the importance in developing
      monitoring plans that support future risk assessments and adaptive management for
      subspecies of cutthroat trout. 

PMID- 24660664
TI  - Anatomic features associated with femoroacetabular impingement are equally common
      in hips of old and young asymptomatic individuals without CT signs of
      osteoarthritis.
AB  - OBJECTIVE: The purpose of this article is to evaluate and compare the prevalence
      and measurement values of CT signs of femoroacetabular impingement (FAI) in
      asymptomatic hips without CT signs of osteoarthritis between two age groups:
      younger than 40 years and older than 60 years. SUBJECTS AND METHODS: We
      prospectively included patients undergoing thoracoabdominopelvic MDCT for
      nonorthopedic indications with asymptomatic hips and excluded hips with signs of
      osteoarthritis seen on CT. Two age groups including 75 hips each were enrolled (<
      40 years old: mean age, 31 years; 15 women; > 60 years old: mean age, 66 years;
      21 women). Two observers independently performed the image analysis. Prevalences
      and quantitative values of the cam (alpha angle and femoral head-neck offset) and
      pincer (acetabular version angle, acetabular index, lateral center-edge angle,
      crossover sign, and posterior wall sign) FAI morphotypes were compared using both
      difference and equivalence tests. Intraobserver agreement was assessed. RESULTS:
      The prevalence of CT signs of FAI were high and showed great variation depending
      on the signs and cutoff values, in both groups (9-63% for cam; 3-50% for pincer).
      The prevalence and measurement values of CT signs of the cam morphotype were
      equivalent between the two age groups. The prevalence and measurement values of
      CT signs of the pincer morphotype were statistically equivalent between the age
      groups except for the acetabular version angle, lateral center-edge angle, and
      crossover sign for which no statistical difference was found, but statistical
      equivalence was not reached. Interobserver and intraobserver agreement were
      moderate to almost perfect (kappa = 0.72-0.89; intraclass correlation
      coefficient, 0.42-0.94). CONCLUSION: The prevalence and measurement values of
      most CT signs of FAI morphotypes were high and equivalent between the two age
      groups of patients with asymptomatic nonosteoarthritic hips.

PMID- 24660665
TI  - Hydatid of Morgagni: sonographic resemblance with ectopic pregnancy.

PMID- 24660667
TI  - Electromembrane Surrounded Solid Phase Microextraction Followed by Injection Port
      Derivatization and Gas Chromatography-Flame Ionization Detector Analysis for
      Determination of Acidic Herbicides in Plant Tissue.
AB  - Electromembrane surrounded solid phase microextraction (EM-SPME) of acidic
      herbicides was studied for the first time. In order to investigate the capability
      of this new microextraction technique to analyze acidic targets, chlorophenoxy
      acid (CPA) herbicides were quantified in plant tissue. 1-Octanol, was sustained
      in the pores of the wall of a hollow fiber and served as supported liquid
      membrane (SLM). Other EM-SPME related parameters, including extraction time,
      applied voltage, and pHs of the sample solution and the acceptor phase, were
      optimized using experimental design. A 20 min time frame was needed to reach the
      highest extraction efficiency of the analytes from a 24 mL alkaline sample
      solution across the organic liquid membrane and into the aqueous acceptor phase
      through a 50 V electrical field, and to their final adsorption on a carbonaceous
      anode. In addition to high sample cleanup, which made the proposed method
      appropriate for analysis of acidic compounds in a complicated media (plant
      tissue), 4.8% of 2-methyl-4-chlorophenoxyacetic acid (MCPA) and 0.6% of 2,4
      dichlorophenoxyacetic acid (2,4-D) were adsorbed on the anode, resulting in
      suitable detection limits (less than 5 ng mL-1), and admissible repeatability and
      reproducibility (intra- and interassay precision were in the ranges of 5.2-8.5%
      and 8.8-12.0%, respectively). Linearity of the method was scrutinized within the
      ranges of 1.0-500.0 and 10.0-500.0 ng mL-1 for MCPA and 2,4-D, respectively, and
      coefficients of determination greater than 0.9958 were obtained. Optimal
      conditions of EM-SPME of the herbicides were employed for analysis of CPAs in
      whole wheat tissue.

PMID- 24660668
TI  - The myth of the team captain as principal leader: extending the athlete
      leadership classification within sport teams.
AB  - Although coaches and players recognise the importance of leaders within the team,
      research on athlete leadership is sparse. The present study expands knowledge of
      athlete leadership by extending the current leadership classification and
      exploring the importance of the team captain as formal leader of the team. An
      online survey was completed by 4,451 participants (31% females and 69% males)
      within nine different team sports in Flanders (Belgium). Players (N = 3,193) and
      coaches (N = 1,258) participated on all different levels in their sports. Results
      revealed that the proposed additional role of motivational leader was perceived
      as clearly distinct from the already established roles (task, social and external
      leader). Furthermore, almost half of the participants (44%) did not perceive
      their captain as the principal leader on any of the four roles. These findings
      underline the fact that the leadership qualities attributed to the captain as the
      team's formal leader are overrated. It can be concluded that leadership is spread
      throughout the team; informal leaders rather than the captain take the lead, both
      on and off the field.

PMID- 24660666
TI  - Peer victimization during middle childhood as a lead indicator of internalizing
      problems and diagnostic outcomes in late adolescence.
AB  - We examined evidence that peer victimization in middle childhood is a lead
      indicator of internalizing behavior problems and diagnostic outcomes during
      adolescence. This research was conducted as part of an ongoing multisite
      longitudinal investigation. The participants were 388 children (198 boys, 190
      girls). Peer victimization was assessed with a peer nomination inventory that was
      administered when the average age of the participants was approximately 8.5
      years. Internalizing problems were assessed using a behavior problem checklist
      completed by mothers in 9 consecutive years, and a structured clinical interview
      was administered to the participants in the summer following high school
      graduation (10-11 years after the victimization assessment). Peer victimization
      in middle childhood was correlated with internalizing problems on a bivariate
      basis through the late years of adolescence. Multilevel analyses also revealed
      associations between peer victimization and increases in internalizing problems
      over time. In addition, peer victimization had a modest link to unipolar
      depressive disorders in late adolescence. Victimization in the peer group during
      middle childhood appears to be a marker of long-term risk for internalizing
      behavior problems and unipolar depression. 

PMID- 24660669
TI  - Population-based estimates for double diabetes amongst people with glucokinase
      monogenic diabetes, GCK-MODY.

PMID- 24660671
TI  - Double-outlet right atrium associated with hypoplastic right heart structures and
      aortic stenosis: echocardiographic features.

PMID- 24660670
TI  - Transcriptional data mining of Salvia miltiorrhiza in response to methyl
      jasmonate to examine the mechanism of bioactive compound biosynthesis and
      regulation.
AB  - Salvia miltiorrhiza is a Chinese herb with significant pharmacologic effects
      because of the bioactive compounds of tanshinones and phenolic acids. Methyl
      jasmonate (MeJA) has been used as an effective elicitor to enhance the production
      of these compounds. However, the molecular mechanism of MeJA-mediated tanshinone
      and salvianolic acid biosynthesis remains unclear. The transcriptional profiles
      of S. miltiorrhiza leaves at 12 h (T12) after MeJA elicitation and mock-treated
      leaves (T0) were generated using the Illumina deep RNA sequencing (RNA-seq)
      strategy to detect the changes in gene expression in response to MeJA. In total,
      37 647 unique sequences were obtained from about 21 million reads, and 25 641
      (71.53%) of these sequences were annotated based on the blast searches against
      the public databases. A total of 5287 unique sequences were expressed
      differentially between the samples of T0 and T12, which covered almost all the
      known genes involved in tanshinone and phenolic acid biosynthesis in S.
      miltiorrhiza. Many of the transcription factors (e.g. MYB, bHLH and WRKY) and
      genes involved in plant hormone biosynthesis and signal transduction were
      expressed differentially in response to the MeJA induction. Importantly, three
      and four candidate cytochrome P450s (P450s) that could be involved in the
      tanshinone and phenolic acid biosynthesis, respectively, were selected from the
      RNA-seq data based on co-expressed pattern analysis with SmCPS1/SmKSL1 and SmRAS,
      which are the key genes responsible for biosynthesis. This comprehensive
      investigation of MeJA-induced gene expression profiles can shed light on the
      molecular mechanisms of the MeJA-mediated bioactive compound biosynthesis and
      regulation in S. miltiorrhiza. 

PMID- 24660673
TI  - Enhancement of couples' communication and dyadic coping by a self-directed
      approach: a randomized controlled trial.
AB  - Although prevention of relationship distress and dissolution has potential to
      strengthen the well-being of partners and any children they are raising,
      dissemination of prevention programs can be limited because couples face many
      barriers to in-person participation. An alternative strategy, providing couples
      with an instructional DVD, is tested in the present study, in which 330 Caucasian
      couples (N = 660 participants; mean age: men 41.4 years, women 40.0 years) were
      randomly assigned to a DVD group without any further support, a DVD group with
      technical telephone coaching, or a wait-list control group. Couples completed
      questionnaires at pretest, posttest, and 3 and 6 months after completion of the
      intervention. Self-report measures of dyadic coping, communication quality,
      ineffective arguing, and relationship satisfaction were used to test whether the
      intervention groups improved in comparison with the control group. Women in both
      intervention groups increased in dyadic coping, reduced conflict behavior, and
      were more satisfied with their relationship 6 months after the intervention.
      Effects for men were mixed. Participants with poorer skills reported stronger
      improvement. Intimate relationships can, within limits, be positively influenced
      by a self-directed approach. Effective dissemination of principles underlying
      successful relationships can be facilitated through the use of emerging low-cost
      tools and technologies.

PMID- 24660672
TI  - A behavioral economic analysis of changes in food-related and food-free
      reinforcement during weight loss treatment.
AB  - OBJECTIVE: Behavioral economic theory predicts that reductions in consumption of
      highly valued commodities, such as drugs or palatable food items, are facilitated
      by increasing engagement in reinforcing substitutes. The current study
      prospectively examines changes in engagement in and enjoyment of food versus food
      free activities during an 18-month behavioral weight loss intervention. METHOD:
      Participants were 202 overweight/obese individuals who took part in an 18-month
      behavioral weight loss treatment and were randomly assigned to a traditional
      hypocaloric, low-fat diet condition or a traditional hypocaloric, low-fat diet
      plus a goal to limit variety in snack food consumption condition. At baseline and
      6, 12, and 18 months, participants were weighed and completed a measure that
      assessed recent frequency of engagement in and enjoyment of a variety of both
      food and food-free activities. RESULTS: Growth models revealed a statistically
      significant decrease in the relative percentage of food-related reinforcement
      (vs. food-free) over time (reinforcement ratio, or RR), with the greatest
      reduction during the first 6 months of treatment. Food-related reinforcement
      decreased over time, and food-free reinforcement increased. Additionally, the RR
      change predicted change in body mass index (BMI) from 0 to 6 months and 0 to 18
      months, such that greater changes in RR were associated with greater changes in
      BMI. CONCLUSIONS: Findings suggest that behavioral weight loss treatment may
      promote a shift away from food-related reinforcement toward food-free
      reinforcement and that this change may predict BMI change. Future interventions
      may consider targeting increasing engagement in enjoyable food-free activities to
      help with long-term maintenance.

PMID- 24660675
TI  - Long-term effects of analysis of the patient-therapist relationship in the
      context of patients' personality pathology and therapists' parental feelings.
AB  - OBJECTIVE: Analysis of the patient-therapist relationship (relationship work) is
      considered a core active ingredient in dynamic psychotherapy. However, there are
      contradictory findings as for whom and under what circumstances these
      interventions are beneficial. This study investigates long-term effects of
      relationship work in the context of patients' level of personality pathology and
      therapists' self-reported parental feelings. METHOD: One hundred outpatients
      seeking psychotherapy for depression, anxiety, and personality disorders were
      randomly assigned to weekly dynamic psychotherapy, either with or without
      relationship work, for 1 year. Personality pathology was evaluated before
      treatment as the sum of fulfilled personality disorder criteria items on the
      Structured Clinical Interview for DSM-III-R Personality Disorders. Therapist
      feelings were assessed using the Feeling Word Checklist-58. The outcome variables
      were the Psychodynamic Functioning Scales and Inventory of Interpersonal
      Problems, measured at pretreatment, midtreatment, posttreatment, 1 year, and 3
      years after treatment termination. RESULTS: A significant interaction of
      treatment group (relationship work vs. no relationship work) by personality
      pathology by parental therapist feelings was present, indicating that parental
      feelings were differentially associated with long-term effects of relationship
      work, depending on the level of personality pathology. In the context of low
      parental feelings, relationship work was positive for all patients. However, when
      parental feelings were stronger, the specific effects of such interventions were
      even more positive for patients with high levels of personality pathology, but
      negative for patients with low levels of personality pathology. CONCLUSION: The
      interaction of parental therapist feelings and patients' personality pathology
      was strongly associated with the long-term specific effects of analysis of the
      patient-therapist relationship.

PMID- 24660678
TI  - Insights on the isolation, biological activity and synthetic protocols of enyne
      derivatives.
AB  - Enyne derivatives isolated from terrestrial plants and fungi have recently
      attracted attention due to their interesting biological activities. It was found
      that these derivatives possess in general potent antiinflammatory activity which
      was attributed to the structural similarity of enynes with the natural
      antiinflammatory agents secreted in the human body. The biosynthesis of some of
      the isolated enynes has been proposed based on detailed isotope labeling studies.
      Computational calculations have been utilized to analyze the conformational
      preferences and forces affecting interaction of some enynes with the target
      binding sites. Synthesis of enynes has been achieved using several coupling
      techniques. In the current review we shed some light on the isolation, biological
      activity, and biosynthetic routes of enynes. We also recount different synthetic
      methodologies developed for the synthesis of compounds containing enyne
      functional group. 

PMID- 24660674
TI  - Treatment engagement and response to CBT among Latinos with anxiety disorders in
      primary care.
AB  - OBJECTIVE: In the current study, we compared measures of treatment outcome and
      engagement for Latino and non-Latino White patients receiving a cognitive
      behavioral therapy (CBT) program delivered in primary care. METHOD: Participants
      were 18-65 years old and recruited from 17 clinics at 4 different sites to
      participate in a randomized controlled trial for anxiety disorders, which
      compared the Coordinated Anxiety Learning and Management (CALM) intervention
      (consisting of CBT, medication, or both) with usual care. Of those participants
      who were randomized to the intervention arm and selected CBT (either alone or in
      combination with medication), 85 were Latino and 251 were non-Latino White; the
      majority of the Latino participants received the CBT intervention in English (n =
      77). Blinded assessments of clinical improvement and functioning were
      administered at baseline and at 6, 12, and 18 months after baseline. Measures of
      engagement, including attendance, homework adherence, understanding of CBT
      principles, and commitment to treatment, were assessed weekly during the CBT
      intervention. RESULTS: Findings from propensity-weighted linear and logistic
      regression models revealed no statistically significant differences between
      Latinos and non-Latino Whites on symptom measures of clinical improvement and
      functioning at almost all time points. There were significant differences on 2 of
      7 engagement outcomes, namely, number of sessions attended and patients'
      understanding of CBT principles. CONCLUSIONS: These findings suggest that CBT can
      be an effective treatment approach for Latinos who are primarily English speaking
      and likely more acculturated, although continued attention should be directed
      toward engaging Latinos in such interventions.

PMID- 24660679
TI  - Indole alkaloids and semisynthetic indole derivatives as multifunctional
      scaffolds aiming the inhibition of enzymes related to neurodegenerative diseases-
      a focus on Psychotria L. Genus.
AB  - Indole alkaloids and synthetic indole derivatives are well known for their
      therapeutic importance. In fact, preclinical and clinical studies had already
      demonstrated several pharmacological activities for these compounds. Here, we
      overview the multifunctional potential of these molecules for the inhibition of
      enzymes related to neurodegenerative disease: acetylcholinesterase (AChE),
      butyrylcholinesterase (BChE), monoamine oxidases A and B (MAO-A and MAO-B). A
      focus will be given on Psychotria L. genus, considering its reported central
      effects. Finally, three Psychotria alkaloids, namely desoxycordiofoline (61),
      bahienoside A (64) and bufotenine (65), along with the synthetic indole
      derivatives (5S)- 5-(1H-indol-3-ylmethyl)imidazolidine-2,4-dione (66), 5-(1H
      indol-3-ylmethyl)-2-thioxoimidazolin-4-one (67), 5-(1Hindol- 3-ylmethyl)-3-methyl
      2-thioxoimidazolidin-4-one (68), and methyl 2-(aminoN-(2-(4-methylcyclohex-3
      enyl)propan- 2-yl)methanethioamino)-3-(1H-indol-3-yl)propanoate (69), were
      evaluated in vitro regarding their interactions with AChE, BChE, MAO-A and MAO-B.
      It was observed that 66 and 68 were able to inhibit MAO-A activity with IC50
      value of 8.23 and 0.07 MUM. Molecular docking calculations were performed in
      order to understand the interactions between both ligands (66 and 68) and MAO-A.
      It was observed that the indole scaffold of both compounds bind into the MAO-A
      active site in the same orientation, establishing van der Waals contacts with
      lipophilic amino acids. Additionally, the hydantoin ring of 66 is able to
      interact by hydrogen bonds with two conserved water molecules in the MAO-A active
      site, while the methyl-thiohydantoin ring of 68 is within hydrogen bond distance
      from the hydrogen atom attached to the (N-5) of FAD cofactor. Taking together,
      our findings demonstrate that the indolyl-hydantoin and indolylmethyl
      thiohydantoin rings might consists of good scaffolds for the development of new
      MAO-A inhibitors possessing neuroprotective properties. 

PMID- 24660680
TI  - Protective mechanism of lignans from Phyllanthus amarus against galactosamine/
      lipopolysaccharide-induced hepatitis: an in-vivo and in-silico studies.
AB  - Phyllanthus amarus is a medicinal herb used in traditional Indian medicine for
      liver disorders. Several researches also show that it acts primarily in the
      liver, but the molecules were unidentified for liver protective activity. This
      study was to determine whether the lignans isolated from P. amarus attenuates the
      D-galactosamine (GalN) / Lipopolysaccharide (LPS)- induced acute hepatitis in
      mice. Standardize mixture of lignans (slPA) isolated from leaves of P. amarus
      using automated chromatographic technique was used for experiments. Experimental
      mice were orally pre-treated with slPA (10, 30 and 100 mg/kg) for 7 days before
      intra-peritoneal injection of GalN/LPS. Acute hepatitis in mice was confirmed by
      significant increase of pro-inflammatory cytokines, and hepatotoxic markers. Pre
      treatment of slPA exhibit significant liver protection in dose dependant mannaer.
      In-silico molecular docking studies also suggests that lignans are preferentially
      more active due to strong binding affinity against pro-inflammatory cytokines; IL
      1beta, IL-6, and TNF-alpha. The electronic parameters of lignans for
      bioavailability, drug likeness and toxicity were within the acceptable limit. In
      vivo and in-silico results suggest that pretreatment of slPA exhibit potent
      hepatoprotection against GalN/LPS-induced hepatitis in mice and the liver
      protective effects may be due to the inhibition of inflammatory mediators.

PMID- 24660681
TI  - Structure based design, synthesis, and evaluation of potential inhibitors of
      steroid sulfatase.
AB  - The activity of the enzyme steroid sulfatase (STS) is high in breast tumors and
      elevated levels of STS mRNA expression have been associated with a poor
      prognosis. Potent STS irreversible inhibitors have been developed, paving the way
      to use this new type of therapy for the treatment of breast cancer. Several small
      molecules belonging to a natural products-inspired library of previously obtained
      inhibitors of tumor cell growth and new molecules planned to be reversible
      inhibitors of this enzyme were docked into STS. Some of the synthesized xanthone
      derivatives, which revealed high scores against STS, namely oxo-9H-xanthene-3,6
      diyl bis(3-chlorobenzoate) (5), 9-oxo-9H-xanthene-3,6-diyl bis(4
      tertbutylbenzoate) (6) and 9-oxo-9H-xanthene-3,6-diyl bis(4-methoxybenzoate) (7)
      showed poor water solubility. Therefore, formulations of these derivatives with
      cyclodextrins were prepared and characterized. The compounds were evaluated
      regarding their effect on the in vitro growth of various human tumor cell lines,
      as well as the effect in STS inhibition, for the compounds with the most
      favorable DeltaG values. Additionally, the capacity of these derivatives and of
      some prenyl and acetoxy-benzophenone and xanthones to inhibit the in vitro growth
      of MCF-7 ER(+) and/or to inhibit STS in a micromolar range was also assessed.
      Some compounds developed in the present work were shown to be potential STS
      inhibitors. 

PMID- 24660682
TI  - Modes of action of arjunolic acid and derivatives on Trypanosoma cruzi cells.
AB  - Chagas disease causes considerable morbimortality in the Americas, with circa 7
      to 8 million infected people, causing at least 12,000 annual deaths and 100
      million people at risk. Its chemotherapy is poorly selective and effective,
      associated to severe side effects and unresponsive cases. Thus, R&D on
      therapeutic alternatives is undoubtedly required. The Brazilian poorly studied
      biodiversity offers uncountable bioagents, which may be exploited for
      chemotherapy. The triterpene arjunolic acid (AA), reduced the Trypanosoma cruzi
      epimastigote in vitro proliferation with an apparent IC50 of 171 uM. Electron
      microscopy analysis revealed remarkable effects on the parasite surface and
      architecture. AA-treated parasites displayed minutely corrugated plasma membranes
      devoid of subpellicular microtubules as well as biogenesis of multiple basal
      bodies. As the AA effects appeared mainly restricted or originated at the
      parasite peripheral cytoplasm, including the cytoskeleton membrane linkage, we
      inferred that the compound targeted primarily the lipid bilayer; therefore, we
      performed synthetic modification to increase the molecule lipophilicity and thus
      membrane permeability. The methyl ester (MeAA) and tri-acetylated derivatives
      (3AcAA) had potentiated trypanocidal activity, producing IC50 values of 21.9 and
      15.8 uM, respectively. Both derivatives were able to produce remarkable
      ultrastructural alterations in the parasites, including inner compartments such
      as Golgi apparatus and the endocytic/autophagic pathway. Parasites cultured with
      both derivatives displayed numerous and large autophagic vacuoles, altered
      flagellar length and cell body connection. These data indicate that synthetically
      modified natural products comprise valuable tools in antiparasitic chemotherapy
      and that electron microscopy may be useful not only in determining the mechanisms
      of action but also in directing such modifications for rational drug design.

PMID- 24660683
TI  - Antitrypanosomal activity & docking studies of isolated constituents from the
      lichen Cetraria islandica: possibly multifunctional scaffolds.
AB  - Chemical investigation of the lichen Cetraria islandica has led to the isolation
      of four compounds identified as protolichesterinic acid, lichesterinic acid,
      protocetraric acid and fumarprotocetraric acid. Their structures were
      characterized using their physical and spectroscopic data. Using an AlamarblueTM
      96 well microplate assay, these compounds were tested to evaluate their
      trypanocidal activity against Trypanosoma brucei brucei. Protolichesterinic acid
      (MIC = 6.30 uM) and lichesterinic acid (MIC = 12.5 uM) showed very significant
      activity against the test organism. Docking studies (GRIP technique) of these
      molecules revealed their strong affinity towards possible targets of Trypanosoma
      brucei such as riboflavin kinase, sterol-14alpha-demethylase (CYP51), rohedsain
      and glutathione synthetase. Hydrophobicity played a significant role in their
      antitrypanosomal activity.

PMID- 24660684
TI  - QSAR guided semi-synthesis and in-vitro validation of anticancer activity in
      ursolic acid derivatives.
AB  - As a part of our anticancer drug discovery programme, QSAR models were developed
      for the prediction of anticancer activities of ursolic acid derivatives against
      the human hepatocellular carcinoma HepG2, breast carcinoma MDA-MB-231 and the
      human ductal breast epithelial T47D cancer cell lines followed by wet lab semi
      synthesis of virtually active derivatives, their in-vitro biological evaluation
      and apoptosis. The development of QSAR models was carried out by forward stepwise
      multiple linear regression method using a leave-one-out approach. Virtually
      active derivatives were semi synthesized, spectroscopically characterized and
      then in-vitro tested against human cancer cell lines. Active derivatives were
      checked via DNA fragmentation assay. The results exhibited regression
      coefficients (r(2)) and the cross-validation regression coefficients (rCV(2)) for
      the human HepG2, MDA-MB-231 and T47D cancer cell lines as .95 and .90; .92 and
      .87; .89 and .83 respectively showing the prediction accuracy of the models
      against biological activities. Computational molecular modeling is a valid modern
      approach, widely used in the identification of potential drug leads. The most
      active virtual derivatives of UA were semi- synthesized and their in-vitro and ex
      vivo evaluation showed similar results with the predicted one, validating our
      QSAR models. Out of several active derivatives, the three UA2, UA7 and UA10 were
      potentially active against the above human cancer cell lines. These findings may
      be of immense importance in the anticancer drug development of an inexpensive and
      widely available natural product, ursolic acid. 

PMID- 24660685
TI  - Novel dual inhibitors of nuclear factor-kappa B (NF-kappaB) and cyclooxygenase- 2
      (COX-2): synthesis, in vitro anticancer activity and stability studies of
      lantadene-non steroidal anti-inflammatory drug (NSAID) conjugates.
AB  - The activation of transcription factors nuclear factor-kappa B (NF-kappa B) and
      cyclooxygenase-2 (COX-2) is critical in cancer; they act synergistically in
      promoting tumor growth, survival, and resistance to chemotherapy. Thus, combined
      targeting of NF-kappa B and COX-2 present an opportunity for synergistic
      anticancer efficacy. The ester prodrugs of pentacyclic triterpenoids reduced
      lantadene A (3), B (4), and its congener 22beta-hydroxyoleanonic acid (5) with
      various non steroidal anti-inflammatory drugs (NSAIDs) present a novel approach.
      The ester prodrugs of 3 and 4 with diclofenac showed promising dual inhibition of
      NF-kappa B and COX-2. The lead prodrugs 14 and 15 exhibited inhibition of
      inhibitor of nuclear factor-kappa B kinasebeta (IKKbeta) in the single-digit
      micromolar range and at the same time, prodrugs 14 and 15 showed marked
      cytotoxicity against A549 lung cancer cell line with IC(50s) 0.15 and 0.42 uM,
      respectively. The prodrugs 14 and 15 exhibited stability in the acidic pH and
      were hydrolyzed readily in the human blood plasma to release the active parent
      moieties. Thus, we have synthesized novel hybrid compounds to target both NF
      kappa B and COX-2 via a prodrug approach, leading to promising anticancer
      candidates.

PMID- 24660686
TI  - Antitrypanosomal activity & docking studies of components of Crateva adansonii DC
      leaves: novel multifunctional scaffolds.
AB  - Chemical investigation of Crateva adansonii DC has led to the isolation of
      aurantiamide acetate, a novel ethyl pyropheophorbide A, purpurin-18 ethyl ester
      and pyropheophorbide A. Their structures were elucidated using extensive spectral
      data. These metabolites were then evaluated for their in vitro bioactivity
      against the African trypanosome Trypanosoma brucei brucei (S427) blood stream
      forms. Anti-trypanosomal activity decreased with aurantiamide acetate (MIC 25uM),
      while it increased with the pheopytins (MIC 6.25uM), when compared to the
      standard drug Suramin. Using the Vlife MDS 4.3 - GRIP docking, these
      phytoconstituents were then tested to identify the proteins targeted and the mode
      of activity employed. Their affinity towards the receptor sites of trypanothione
      reductase, riboflavin kinase, rohedsain, glutathione synthetase & sterol-14alpha
      demethylase (CYP51) of Trypanosoma brucei were evaluated according to the
      resulting docking energies.

PMID- 24660687
TI  - Parent-child conflict and drug use in college women: a moderated mediation model
      of self-control and mindfulness.
AB  - This cross-sectional study examined the association between parent-child conflict
      and illicit drug use in a sample of female college students (N = 928). The
      mediating roles of self-control and mindfulness, as well as an interaction
      between self-control and mindfulness, were examined in a moderated mediation
      model for the purposes of expanding etiological theory and introducing targets
      for the prevention and treatment of drug abuse. Whereas deficits in self-control
      were found to facilitate the positive relation observed between parent-child
      conflict and the likelihood of experiencing drug-related problems, an interaction
      between mindfulness and self-control helped explain the association between
      parent-child conflict and intensity of drug-related problems. Parent-child
      conflict was related to low mindfulness when self-control was low, and low
      mindfulness in turn was related to a higher intensity of drug-related problems.
      This association did not exist for women with high self-control. Findings are
      consistent with developmental research on the etiology of drug use and the
      protective properties of mindfulness and self-control. Mindfulness as a potential
      target of intervention for drug users with low self-control to prevent drug
      related problems is explored.

PMID- 24660688
TI  - The therapist, the client, and the real relationship: an actor-partner
      interdependence analysis of treatment outcome.
AB  - The relationship between treatment progress (as rated by both clients and
      therapists) and real relationship (also rated by both clients and therapists) was
      decomposed into between-therapist and within-therapist (between-client) effects
      and analyzed using the actor-partner interdependence model. We reanalyzed a
      subset of the data, 12 therapists and 32 clients, from Gelso et al.'s (2012)
      study of brief, theoretically diverse outpatient treatment. Consistent with and
      extending previous research, clients whose therapists provided higher average
      levels of client-perceived real relationship across the clients treated by a
      given therapist had better progress ratings from both themselves and their
      therapists. Within each therapist's caseload, differences between clients in
      client- or therapist-rated real relationship were unrelated to either client- or
      therapist-rated outcome. Clients whose therapists provided higher average levels
      of therapist-perceived real relationship, across the clients treated by the
      therapist, had worse progress ratings from the therapists. The results provide
      additional evidence for the importance of between-therapist differences in
      therapeutic relationship qualities, both client and therapist rated.

PMID- 24660689
TI  - Naturalistic interpersonal behavior patterns differentiate depression and anxiety
      symptoms in the community.
AB  - Symptoms of depression and anxiety are associated with interpersonal problems
      that, in turn, exacerbate and maintain these symptoms. The purpose of the present
      study was to identify patterns of interpersonal behavior characteristic of each
      syndrome, particularly whether intraindividual variability in interpersonal
      behavior differentiates between anxiety and depression symptoms. After reporting
      on depression and anxiety symptoms, community participants recorded their
      behavior following interpersonal interactions over 21 days. Participants'
      interpersonal behavior at each event was measured using behavior dimensions from
      the interpersonal circumplex: dominant, submissive, agreeable, and quarrelsome.
      Mean levels of behavior and intraindividual variability were computed over events
      and then regressed on depression and anxiety symptoms using structural equation
      modeling. Elevations in reported depression and anxiety symptoms were both
      associated with elevated mean-level quarrelsome and submissive behavior.
      Independent of mean-level behavior and concurrent depression symptoms, elevated
      anxiety symptoms were associated with elevated variability in agreeable,
      dominant, and submissive behavior and with elevated variability in type of
      interpersonal behavior (i.e., spin). Depression symptoms were unrelated to
      variability in interpersonal behavior. Results demonstrate that variability in
      behavior distinguishes anxiety from depression symptoms.

PMID- 24660690
TI  - Teasing apart the relations between age, birth cohort, and vocational interests.
AB  - Empirical evidence supports that aging is related to differences in work
      attitudes and motivation (Inceoglu, Segers, & Bartram, 2012; Kooij, de Lange,
      Jansen, Kanfer, & Kikkers, 2011; Ng & Feldman, 2008, 2010), but little research
      has explored the relations between age and vocational interests. Furthermore,
      recent studies of age and work attitudes suggest that generational experiences
      (i.e., birth year) may account for age differences in the workplace (Inceoglu et
      al., 2012; Ng & Feldman, 2008, 2010), which in turn suggests that researchers
      need to incorporate both age and birth cohort effects in their designs. Thus,
      this study was designed to explore the relations of age at the time of testing
      and birth year to vocational interests using a sample of adults (N = 1,792)
      collected over a period of 3 decades. As expected, age was not a significant
      predictor of most interests, but birth year also was not found to predict most
      interests, with the significant prediction of Realistic interests by both age and
      birth year being the exception. Gender, however, significantly predicted most
      areas of interests. Neither age nor gender moderated any relationships between
      birth year and interests. Results suggest that birth year and age were minimally
      related to interests as all effect sizes were small. Discussion of the results
      illustrates the need for further research on this issue and also offers
      considerations for attracting and retaining different generations of workers in
      light of the findings.

PMID- 24660691
TI  - Preliminary development and validation of the Supervisee Attachment Strategies
      Scale (SASS).
AB  - The influence of counselor trainees' adult attachment orientations in the context
      of supervision has the potential to inform both training and supervision
      practice. However, the pursuit of such research requires the availability of
      appropriate assessment tools. The present study describes the development and
      validation of the Supervisee Attachment Strategies Scale (SASS), a theory-based
      measure of counseling trainees' attachment orientations toward their clinical
      supervisors. Participants were recruited online through their training directors
      at Association of Psychology Postdoctoral and Internship Centers member programs.
      Data were nationally collected from 352 trainees representing programs in the
      United States and Canada. Exploratory factor analysis yielded 2 interpretable
      factors along the adult attachment dimensions of avoidance vs. engagement and
      rejection concern vs. security. These 2 factors accounted for 55.85% of the
      interitem variance in the rotated solution of the 22-item SASS scale. SASS
      subscale scores were negatively correlated with the supervisory working alliance
      and predicted greater endorsement of role conflict and role ambiguity in the
      current supervisory relationship. Higher avoidance (but not rejection concern)
      predicted diminished perceptions of satisfaction with the overall training
      experience. Findings from this study suggest that trainees who engaged in
      adaptive attachment strategies may be more likely to address conflict, negotiate
      additional explorative opportunities in training, and seek out their supervisors
      in times of uncertainty.

PMID- 24660692
TI  - Influence of a support group for young women with disabilities on sense of
      belonging.
AB  - Women and girls with disabilities face obstacles to community participation and
      social acceptance. Consequently, as adolescent women with disabilities mature
      into adulthood, they may have difficulty feeling that they belong both in the
      general community and in the community of all women. The positive impact of peer
      support groups for young women with disabilities on their sense of belonging has
      been underinvestigated. We conducted in-depth, semistructured interviews with 9
      members of a well-established empowerment support group for young women with
      disabilities to explore how the group might foster a sense of belonging to the
      general community as well as a sense of shared womanhood. Results revealed that
      self-confidence and disability pride stemming from participation in the group
      were essential in helping the women counteract exclusionary messages from the
      outside world. The group provided an opportunity to develop a positive disability
      identity and to gain new information regarding the ability and right to identify
      as women. Reciprocal bonds with other group members helped cultivate feelings of
      belonging. In turn, the women communicated their empowered identities and the
      disability rights information they learned in the group to their friends, family,
      and community members. The group offered the women various platforms to assert
      their right to belong and, therefore, to participate in the world as women and as
      independent members of their broader communities. These results show how peer
      support groups for young women with disabilities can positively influence their
      sense of belonging both within the group and in the world outside the group.

PMID- 24660693
TI  - Investigating the structure and measurement invariance of the Multigroup Ethnic
      Identity Measure in a multiethnic sample of college students.
AB  - In this article, we evaluate the factor structure of the Multigroup Ethnic
      Identity Measure (MEIM; Phinney, 1992) and test whether the MEIM exhibits
      measurement invariance across ethnic groups taken from a diverse sample of
      students from 30 different colleges and universities across the United States (N
      = 9,625). Initial analyses suggested that a bifactor model was an adequate
      representation of the structure of the MEIM. This model was then used in
      subsequent invariance tests. Results suggested that the MEIM displayed configural
      and metric invariance across 5 diverse ethnic groups (i.e., White, Black,
      Hispanic, East Asian, and South Asian). There were indications that the MEIM
      displayed a similar factor structure with roughly equivalent factor loadings
      across diverse ethnic groups. However, there was little evidence of scalar
      invariance across these groups, suggesting that mean-level comparisons of MEIM
      scores across ethnic groups should be interpreted with caution. The implications
      of these findings for the interpretation and use of this popular measure of
      ethnic identity are discussed.

PMID- 24660695
TI  - In vivo CT dosimetry during CT colonography.
AB  - OBJECTIVE: The purpose of this study was to develop a method of measuring rectal
      radiation dose in vivo during CT colonography (CTC) and assess the accuracy of
      size-specific dose estimates (SSDEs) relative to that of in vivo dose
      measurements. MATERIALS AND METHODS: Thermoluminescent dosimeter capsules were
      attached to a CTC rectal catheter to obtain four measurements of the CT radiation
      dose in 10 volunteers (five men and five women; age range, 23-87 years; mean age,
      70.4 years). A fixed CT technique (supine and prone, 50 mAs and 120 kVp each) was
      used for CTC. SSDEs and percentile body habitus measurements were based on CT
      images and directly compared with in vivo dose measurements. RESULTS: The mean
      absorbed doses delivered to the rectum ranged from 8.8 to 23.6 mGy in the 10
      patients, whose mean body habitus was in the 27th percentile among American
      adults 18-64 years old (range, 0.5-67th percentile). The mean SSDE error was 7.2%
      (range, 0.6-31.4%). CONCLUSION: This in vivo radiation dose measurement technique
      can be applied to patients undergoing CTC. Our measurements indicate that SSDEs
      are reasonable estimates of the rectal absorbed dose. The data obtained in this
      pilot study can be used as benchmarks for assessing dose estimates using other
      indirect methods (e.g., Monte Carlo simulations).

PMID- 24660696
TI  - Correlation of pulmonary function indexes determined by low-dose MDCT with
      spirometric pulmonary function tests in patients with chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: The objective of our study was to evaluate the correlation between
      pulmonary function indexes determined by low-dose MDCT and those obtained from
      routine spirometric pulmonary function tests (PFTs) in patients with chronic
      obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Lung function of
      patients with COPD stages 0-III was evaluated by both MDCT and spirometric PFTs.
      Scanning was performed at maximum end-inspiration and maximum end-expiration.
      RESULTS: A very strong correlation was found between extrapolated expiratory lung
      volume (LVex) and COPD stage (r = 0.802, p < 0.001) and between extrapolated LVex
      and the ratio of forced expiratory volume in 1 second and percentage forced vital
      capacity (FEV1/FVC%) (r = -0.831, p < 0.001). Moreover, strong positive
      correlations were found between inspiratory lung volume (LVin) and total lung
      capacity (TLC) (r = 0.658, p < 0.001), LVex and residual volume (RV) (r = 0.683,
      p < 0.001), extrapolated LVex and RV (r = 0.640, p < 0.001), LVex and RV/TLC (r =
      0.602, p < 0.001), LVex/LVin and RV/TLC (r = 0.622, p < 0.001), extrapolated LVex
      and RV/TLC (r = 0.663, p < 0.001), and LVex and COPD stage (r = 0.697, p <
      0.001). CONCLUSION: Low-dose MDCT lung function indexes correlate well with
      spirometric PFT results, and the highest correlation is at end-expiration. Low
      dose MDCT may be useful for evaluating lung function in patients with COPD.

PMID- 24660697
TI  - Relationship between quantitative CT of pulmonary small vessels and pulmonary
      perfusion.
AB  - OBJECTIVE: The relationship between morphologic alterations of pulmonary small
      vessels and pulmonary perfusion has not been clarified. The purpose of this study
      was to evaluate the relationship between the cross-sectional area (CSA) of
      pulmonary small vessels alterations measured on CT images and pulmonary perfusion
      on lung perfusion scintigraphy. MATERIALS AND METHODS: This study comprised 46
      subjects who underwent both CT and lung perfusion scintigraphy. We measured CSA
      of pulmonary small vessels less than 5 mm(2) and 5-10 mm(2) using CT images and
      obtained the percentage of the right lung to whole lung in each CSA group
      (CSA<5,R/W and CSA5-10,R/W, respectively). Using (99m)Tc-macroaggregated albumin
      (MAA) lung perfusion scintigraphy, we obtained right and total lung counts and
      calculated the percentage of the right to whole-lung counts (MAAR/W). Those CT
      and scintigraphy measurements were also calculated separately each in right
      upper, right lower, left upper, and left lower zones. The correlations of
      CSA<5,R/W and CSA5-10,R/W with MAAR/W, the correlation between the percentage of
      each lung zone to whole-lung CSA<5 and the percentage of each corresponding lung
      zone to whole-lung MAA were evaluated. RESULTS: The mean CSA<5,R/W was 58.1% +/-
      11.2%, and the mean MAAR/W was 59.3% +/- 17.9%. CSA<5,R/W had a significant
      correlation with MAAR/W (rho = 0.865, p < 0.0001), whereas significant
      correlation was found but was relatively weak between CSA5-10,R/W and MAAR/W (rho
      = 0.512, p = 0.0003). The percentage of each lung zone to whole-lung CSA<5 had
      significant correlations with the percentage of each corresponding lung zone to
      whole-lung MAA. CONCLUSION: Pulmonary small vessels alteration, as measured by
      CSA on CT images, significantly correlated with pulmonary perfusion.

PMID- 24660698
TI  - Coronary artery calcification is often not reported in pulmonary CT angiography
      in patients with suspected pulmonary embolism: an opportunity to improve
      diagnosis of acute coronary syndrome.
AB  - OBJECTIVE: In patients with suspected pulmonary thromboembolism (PTE), coronary
      artery calcification (CAC) can be an incidental finding on pulmonary CT
      angiography. We evaluated the frequency of CAC not being reported and its
      association with a diagnosis of acute coronary syndrome (ACS). MATERIALS AND
      METHODS: Data of 469 consecutive patients who were referred to the emergency
      radiology department for pulmonary CT angiography of suspected PTE were reviewed.
      Radiology reports were rechecked and positive CAC findings were recorded. All
      pulmonary CT angiograms were reevaluated by one radiologist and CAC findings were
      recorded. The rates of ACS and PTE as final diagnoses for that hospital admission
      were calculated. The association between CAC and ACS diagnosis was assessed in
      different subgroups of patients. RESULTS: Approximately 11.1% of patients had PTE
      and 43.8% had CAC. The incidence of CAC was significantly higher in patients with
      an ACS diagnosis than in those without ACS (56.2% vs 40.4%, respectively; odds
      ratio [OR] = 1.9). There was a strong positive association (OR = 3.5) between CAC
      and ACS in younger patients (men <= 45 years and women <= 55 years), patients
      without PTE (OR = 2.2), and those without cardiometabolic risk factors (OR =
      3.8). CAC was not reported in 45% of patients (n = 98) with positive CAC findings
      on imaging. ACS was the final diagnosis in 31.6% of patients with unreported CAC.
      There was a significant association between CAC and ACS in patients with
      unreported CAC (OR = 2.2). This association was more prominent in the subgroups
      described. CONCLUSION: CAC is often not reported in pulmonary CT angiography
      studies. CAC is a significant predictor of ACS particularly in younger patients,
      patients without PTE, and those without cardiometabolic risk factors. Especially
      in these subgroups, radiologists should assess CAC findings.

PMID- 24660699
TI  - Diagnostic performance of algorithm for computer-assisted detection of
      significant coronary artery disease in patients with acute chest pain: comparison
      with invasive coronary angiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance of an
      automated computer-assisted detection (CAD) algorithm to detect coronary artery
      stenosis on coronary CT angiography (CTA). MATERIALS AND METHODS: We investigated
      128 consecutive patients (76 men, 52 women; mean [SD] age, 64 +/- 11 years) who
      had acute chest pain and underwent 128-slice dual-source coronary CTA and
      invasive coronary angiography at an emergency department. All coronary CTA data
      were analyzed using customized software for the detection of coronary artery
      stenosis without human interaction. The diagnostic performance of a CAD algorithm
      for evaluation of stenosis of at least 50% of vessel diameter was compared with
      that of human interpretation of coronary CTA, with invasive coronary angiography
      as a reference standard. RESULTS: Of the 128 patients, 25 patients were excluded
      because of failure of data processing (n = 9) or history of stent insertion or
      coronary artery bypass graft (n = 16). Invasive coronary angiography revealed
      significant stenosis in 62% (64/103) of the remaining patients. In detecting
      significant stenosis, the CAD algorithm yielded 100% sensitivity, 23.1%
      specificity, 68.1% positive predictive value (PPV), and 100% negative predictive
      value (NPV) in per-patient analysis. On per-vessel analysis, the CAD algorithm
      yielded 90.0% sensitivity, 62.4% specificity, 40.1% PPV, and 95.7% NPV. Human
      interpretation of coronary CTA yielded 98.4% and 96.7% sensitivities, 79.5% and
      95.0% specificities, 88.7% and 84.5% PPVs, and 96.9% and 99.0% NPVs for
      diagnosing significant stenosis on per-patient and per-vessel analyses,
      respectively. CONCLUSION: The CAD algorithm yields a high NPV in detecting
      stenosis of at least 50% on coronary CTA. As a second "reader," the CAD algorithm
      may help to exclude significant coronary stenosis in patients with acute chest
      pain at an emergency department.

PMID- 24660700
TI  - Missed pulmonary embolism on abdominal CT.
AB  - OBJECTIVE: The purpose of this study is to evaluate a series of missed pulmonary
      emboli (PE) identified on abdominal CT and to describe their characteristics and
      the clinical scenario. MATERIALS AND METHODS: All reports of chest CT scans
      performed during a 12-month period were searched for keywords indicative of PE.
      Among patients with PE, patients who also underwent an enhanced abdominal CT
      within 3 months were assessed for missed PE. Three radiologists reviewed the
      abdominal CT to confirm the presence of a missed PE. Missed PEs were classified
      as unknown or known. Each study was assessed for characteristics of the missed PE
      and the image quality of the PE study. The electronic medical record was used to
      document the clinical context in which the PE occurred. RESULTS: Eighteen
      patients (12 men and six women; average age, 58.8 years) were identified as
      having missed PE on abdominal CT. In seven patients (38.9%), the PE had not been
      previously diagnosed. Most of the missed PEs were segmental, but three missed PEs
      occurred in lobar vessels. In a slight majority of the cases, the reviewing
      radiologists judged the contrast bolus as good. The abdominal CT on which PE was
      overlooked was obtained for a variety of reasons, most commonly because of
      abdominal pain or to follow up a preexisting condition. CONCLUSION: This study
      shows that missed PE can occur on abdominal CT. It is recommended that
      interpretation include a careful search of the lower pulmonary arterial
      vasculature on contrast-enhanced abdominal CT scans.

PMID- 24660701
TI  - Local recurrence after chemoembolization of hepatocellular carcinoma: uptake of
      gadoxetic acid as a new prognostic factor.
AB  - OBJECTIVE: The purpose of this article is to investigate whether there is a
      difference in susceptibility to transcatheter arterial chemoembolization between
      hepatocellular carcinomas (HCCs) showing high uptake and those showing low uptake
      of gadoxetic acid in the hepatobiliary phase of MRI. MATERIALS AND METHODS: One
      hundred HCCs that achieved optimal chemoembolization, as assessed by immediate CT
      in 60 patients, were classified as having high (n = 19) or low (n = 81) uptake of
      gadoxetic acid on MRI performed before chemoembolization. The local recurrence
      rates were estimated using the Kaplan-Meier method, and differences between the
      groups were compared using the log-rank test. The following factors were also
      correlated with the local recurrence rate using the Cox proportional hazards
      model for a univariate analysis: high uptake of gadoxetic acid, number of feeding
      arteries, extrahepatic arterial supply, Child-Pugh class, clinical tumor stage,
      size, location, and iodized oil accumulation in the noncancerous tissue
      surrounding the lesion. Parameters that were significant at p < 0.05 were entered
      into a multivariate model. RESULTS: The 1- and 3-year local recurrence-free rates
      were 95% in high-uptake HCCs and 66% and 54%, respectively, in low-uptake HCCs
      (log-rank test, p < 0.01). The low uptake of gadoxetic acid was the only
      significant predictor of early local recurrence (hazard ratio = 9.24; p = 0.03)
      by multivariate analysis. CONCLUSION: HCCs showing high uptake of gadoxetic acid
      appear to be susceptible to chemoembolization.

PMID- 24660702
TI  - Natural history of hepatic steatosis: observed outcomes for subsequent liver and
      cardiovascular complications.
AB  - OBJECTIVE: Hepatic steatosis is a common incidental finding at radiologic
      imaging. The natural history of nonalcoholic fatty liver disease (NAFLD) and its
      associated risks for cardiovascular complications are not well established in
      this context. Our purpose was to investigate the clinical outcome of moderate-to
      severe hepatic steatosis detected incidentally at CT. MATERIALS AND METHODS:
      Liver attenuation was measured at unenhanced CT in 4412 consecutive adults
      scanned over a 12-month period. Moderate-to-severe steatosis was diagnosed by
      liver attenuation less than or equal to 45 HU, which is essentially 100% specific
      for histologic grading of 30% or more fat content. The control group was defined
      by a high-normal liver attenuation of 60-65 HU. The main exclusion criteria were
      preexisting liver disease (beyond asymptomatic NAFLD), alcoholism, or less than 1
      year of clinical follow-up. A medical record review assessed for the development
      of symptomatic liver disease (including nonalcoholic steatohepatitis and
      cirrhosis) and seminal cardiovascular events (myocardial infarction,
      cerebrovascular accident, transient ischemic attacks, or coronary bypass or
      stent). Data for body mass index, diabetes, and liver enzyme levels were also
      recorded. RESULTS: Five hundred three adults (11.4%) had unenhanced CT liver
      attenuation of 45 HU or less, yielding a final steatosis cohort of 282 patients
      after exclusions; the control group consisted of 768 patients after exclusions.
      The mean (+/- SD) patient age (51.4 +/- 14.7 vs 50.8 +/- 17.4 years), sex (53.9%
      vs 54.7% female), and mean follow-up intervals (7.3 +/- 3.2 vs 7.7 +/- 3.2 years)
      were similar between groups. No patient in either group had progression of liver
      disease beyond incidental steatosis. Subsequent cardiovascular events were more
      common in the steatosis cohort (9.9% vs 5.9%; p = 0.028), but steatosis was not
      an independent risk factor after controlling for diabetes and body mass index in
      multiple logistic regression analysis. CONCLUSION: This longitudinal study failed
      to show progression of moderate-to-severe hepatic steatosis to symptomatic forms
      of fatty liver disease over a 5- to 10-year time horizon. Aggressive workup of
      hepatic steatosis found incidentally on imaging does not appear to be warranted.
      Steatosis was a biomarker for subsequent cardiovascular events but not an
      independent risk factor.

PMID- 24660703
TI  - Cystic fibrosis: unenhanced CT description of the appendix in asymptomatic
      adults.
AB  - OBJECTIVE: The purpose of this study was to describe the unenhanced CT appearance
      of the appendix in adults with cystic fibrosis. SUBJECTS AND METHODS: Among
      adults with cystic fibrosis undergoing follow-up at our hospital, 71 patients (35
      women, 36 men; mean age, 33 years; range, 18-59 years) without a history of
      appendectomy or current abdominal pain were prospectively included in this study
      and underwent unenhanced abdominopelvic MDCT. Two readers coded visualization of
      the appendix, measured the diameter of the appendix, and described the
      attenuation of its contents in relation to the intestinal wall. They also coded
      the presence of colonic wall redundancy, pancreatic fatty replacement, and
      cirrhosis. Lung transplant status and CFTR gene mutations were recorded. Analysis
      of variance, linear regression analysis, Student t test, and Pearson test were
      used. RESULTS: The appendix was detected in all patients. The mean diameter was
      recorded as 10.6 +/- 3.5 mm. The mean diameter was larger when the appendix
      contained hyperattenuating material (p = 0.001). There was no association between
      diameter and the other coded CT findings (p = 0.076-0.466), transplant status (p
      = 0.788), or CFTR mutation (p = 0.078). In 75% of the patients, the appendix
      contained hyperattenuating material with a higher proportion in homozygous
      DeltaF508 mutation (p = 0.029) without any significant effect of the other CT
      features (p = 0.056-0.392), or transplant status (p = 1.000). CONCLUSION: The
      appendix is larger in adults with cystic fibrosis than in those without it and
      appears hyperattenuating at unenhanced CT in 75% of patients, more commonly in
      those with DeltaF508 homozygous mutation.

PMID- 24660704
TI  - Comparison of T2-weighted MRI with and without fat suppression for
      differentiating renal angiomyolipomas without visible fat from other renal
      tumors.
AB  - OBJECTIVE: The purpose of this study was to retrospectively compare the
      usefulness of T2-weighted imaging with and without fat suppression for
      differentiating angiomyolipomas (AMLs) without visible fat from other renal
      tumors. MATERIALS AND METHODS: MRI was performed in 111 patients (66 men and 46
      women; age range, 17-78 years) who had pathologically diagnosed (14 AMLs, 86
      renal cell carcinomas [RCCs], and three other tumors) and clinically diagnosed
      (eight AMLs) renal masses without visible fat or a cystic portion on unenhanced
      CT. The signal intensity (SI), tumor-to-kidney SI ratio, tumor-to-spleen SI ratio
      on T2-weighted imaging and fat-suppressed T2-weighted imaging, and tumor-fat
      subtraction index were measured for each tumor. Receiver operating characteristic
      (ROC) analysis was used to evaluate diagnostic accuracy of SI ratios. RESULTS:
      The highest area under the ROC curve was 0.886 for tumor-to-kidney SI ratio on
      fat-suppressed T2-weighted imaging. With a tumor-to-kidney SI ratio of 0.9 on fat
      suppressed T2-weighted imaging, the sensitivity, specificity, positive predictive
      value, and negative predictive value were 90.9%, 71.1%, 43.5%, and 97%,
      respectively. The highest tumor-to-kidney SI ratio of AMLs without visible fat
      was 1.09. Ninety-eight percent of renal tumors with a tumor-to-kidney SI ratio
      greater than 1.09 were RCCs (51/52), especially clear cell RCCs (82.7%, 43/52).
      CONCLUSION: Fat-suppressed T2-weighted imaging is more useful than T2-weighted
      imaging for differentiating AMLs without visible fat from non-AMLs. The high SI
      of solid renal masses on fat-suppressed T2-weighted imaging can be indicative of
      non-AMLs, especially RCCs.

PMID- 24660705
TI  - Value of diffusion-weighted imaging at 3 T for prediction of extracapsular
      extension in patients with prostate cancer: a preliminary study.
AB  - OBJECTIVE: The purpose of this study was to retrospectively investigate the value
      of adding diffusion-weighted imaging (DWI) to T2-weighted imaging for the
      prediction of extracapsular extension (ECE) in patients with prostate cancer, as
      well as to compare apparent diffusion coefficients (ADCs) between patients with
      and without ECE. MATERIALS AND METHODS: Seventy-six patients with suspected
      prostate cancer underwent T2-weighted imaging and DWI at 3 T using a phased-array
      coil, followed by radical prostatectomy. For prediction of ECE, the prostate was
      divided into six sectors. Two experienced radiologists analyzed T2-weighted
      images alone and in combination with DWI in consensus and rated the likelihood of
      ECE on a five-point scale. Tumor ADC values were measured, and the results were
      compared between patients with and without ECE. RESULTS: Of the 456 sectors
      studied, 74 (16%) were positive for ECE in 31 patients. For prediction of ECE,
      the specificity and accuracy of combined T2-weighted imaging and DWI were 94.5%
      and 91.7%, respectively, superior to those of T2-weighted imaging alone (87.2%
      and 81.2%, respectively) (p < 0.001). On receiver operating characteristic
      analysis, the area under the curve (Az) of combined T2-weighted imaging and DWI
      (Az = 0.900) was significantly greater than that of T2-weighted imaging alone (Az
      = 0.828) (p < 0.001). The mean tumor ADC values were significantly lower in
      patients with ECE than patients without ECE (p < 0.001). CONCLUSION: DWI at 3 T
      in addition to T2-weighted imaging improves the ability to predict ECE in
      patients with prostate cancer. Furthermore, tumor ADC values in patients with and
      without ECE are significantly different.

PMID- 24660706
TI  - Dynamic contrast-enhanced MR renography for renal function evaluation in
      ureteropelvic junction obstruction: feasibility study.
AB  - OBJECTIVE: The purpose of this study was to evaluate split renal function,
      estimate single-kidney renal function, and identify cause of obstruction in
      patients with ureteropelvic junction (UPJ) obstruction by using contrast-enhanced
      dynamic MR renography (MRR). MATERIALS AND METHODS: Seventeen patients with UPJ
      obstruction underwent MRR and diuresis nuclear renography. Nuclear renography
      assessment of split renal function and mechanical versus functional obstruction
      served as the reference standard. The Baumann-Rudin model for determining
      glomerular filtration rate (GFR) was applied to generate single-kidney renal
      function (SK-GFRMRR) from MRR cortical and medullary enhancement curves. MRR
      split renal function of the right kidney (SK-GFRMRR of the right kidney
      normalized to the sum of SK-GFRMRR of both kidneys) was compared with nuclear
      renography. The MRR estimate of total GFR (eGFRMRR) was compared with that
      derived from Modification of Diet in Renal Disease (MDRD) formula (eGFRMDRD).
      Renal pelvic rate of signal intensity change (PUR) was compared between
      functionally and mechanically obstructed kidneys. RESULTS: There was excellent
      correlation between MRR and nuclear renography measure of split renal function
      ratio (r = 0.87, p < 0.01), with mean difference of less than 10%. There was
      moderate correlation (r = 0.60, p = 0.01) between eGFRMRR and eGFRMDRD. eGFRMRR
      underestimated eGFRMDRD, with mean difference of 13.3 mL/min/1.73 m(2). PUR in
      mechanically obstructed units was significantly lower (0.39 +/- 0.26 vs 2.0 +/-
      1.38 min(-1); p < 0.01) compared with functionally obstructed units. PUR
      discriminated mechanical from functional obstruction with accuracy of 89%.
      CONCLUSION: In patients with UPJ obstruction, MRR can measure split renal
      function, estimate eGFRMDRD with moderate correlation, and accurately
      discriminate mechanical from functional obstruction, thus potentially providing a
      "one-stop shop" examination.

PMID- 24660707
TI  - The challenges in assessing contrast-induced nephropathy: where are we now?
AB  - OBJECTIVE: The objective of our study was to exposit the shifting perspectives on
      contrast-induced nephropathy (CIN) for IV low-osmolar iodinated contrast media.
      CONCLUSION: The historically inflated risk of CIN reflects logistic and
      intellectual pitfalls that continue to confound the study of this disease. Recent
      advances have clarified that the incidence of CIN is much lower than previously
      thought, but there are lingering questions. We suggest that CIN is likely real
      but is rare and offer directions for future study.

PMID- 24660708
TI  - Improving the availability of clinical history accompanying radiographic
      examinations in a large pediatric radiology department.
AB  - OBJECTIVE: The purpose of this quality improvement initiative was to improve the
      consistency with which radiologists are provided a complete clinical history when
      interpreting radiography examinations performed in the outpatient and emergency
      department settings. MATERIALS AND METHODS: The clinical history was considered
      complete if it contained three elements: nature of the symptoms, description of
      injury, or cause for clinical concern; duration of symptoms or time of injury;
      and focal site of pain or abnormality, if applicable. This was reduced to three
      elements: "what-when-where." A goal was established that 95% of the clinical
      histories should contain all three elements. To achieve this goal, technologists
      supplemented referring clinicians' history. The project was divided into four
      phases: launch, support, transition to sustainability, and maintenance. During
      the support phase, results of automated weekly audits automatically populated
      group-level performance reports. During the transition to the sustainability
      phase, audit results populated individual-level performance reports. During the
      maintenance phase, quarterly audit results were incorporated into technologists'
      employee performance goals. RESULTS: Before initiation of the project, 38%
      (76/200) of radiography examinations were accompanied by a complete clinical
      history. This increased to 92% (928/1006) by the end of the 15-week improvement
      phase. Performance was sustained at 96% (1168/1213) 7 months later [corrected].
      CONCLUSION: By clearly defining expectations for an appropriate clinical history
      and establishing system and organizational mechanisms to facilitate verifiable
      compliance, we were able to successfully and sustainably improve the consistency
      with which radiography examinations were accompanied by a complete clinical
      history.

PMID- 24660709
TI  - Improving imaging utilization through practice quality improvement (maintenance
      of certification part IV): a review of requirements and approach to
      implementation.
AB  - OBJECTIVE: The purposes of this article are to review the American Board of
      Radiology requirements for practice quality improvement and to describe our
      approach to improving imaging utilization while offering a guide to implementing
      similar projects at other institutions, emphasizing the plan-do-study-act
      approach. CONCLUSION: There is increased emphasis on improving quality in health
      care. Our institution has undertaken a multiphase practice quality improvement
      project addressing the appropriate utilization of screening cervical spinal CT in
      an emergency department.

PMID- 24660710
TI  - MRI features of extramedullary myeloma.
AB  - OBJECTIVE: The purpose of this study was to describe the MRI features of
      extramedullary myeloma and to evaluate the role of MRI in extramedullary myeloma.
      MATERIALS AND METHODS: The cases of 28 patients (15 men, 13 women; mean age,
      57.53 years; range, 34-83 years) with extramedullary myeloma who underwent MRI at
      one institution from January 2004 through December 2012 were retrospectively
      identified through an electronic search of an institutional radiology database.
      Two radiologists reviewed images from 44 MRI examinations in consensus to
      document the morphologic, signal-intensity, and enhancement characteristics of
      extramedullary myeloma. Electronic medical records were reviewed to document the
      indication for MRI and subsequent management of extramedullary myeloma. RESULTS:
      A total of 72 sites of extramedullary myeloma were noted, most commonly the
      paraspinal-epidural location (28/72, 39%). Two radiologic patterns were
      identified: lesions contiguous with bone (n = 44) and lesions noncontiguous with
      bone (n = 28). Lesions contiguous with bone were larger (p = 0.001; Student t
      test). Of 28 paraspinal-epidural lesions, 13 compressed the cord. Compared with
      skeletal muscle, most of the lesions were hypointense to isointense on T1
      weighted images (67/72, 93.1%) and isointense to hyperintense on T2-weighted
      images (62/72, 86.1%). Lesions noncontiguous with bone were more often
      hypointense on T2-weighted images (8/28 vs 2/44; p = 0.006; Fisher exact test).
      Neurologic symptoms prompted MRI in most cases (n = 32/44). MRI was helpful in
      management by radiotherapy and surgery (19/28). CONCLUSION: Extramedullary
      myeloma can be contiguous or noncontiguous with bone. Lesions contiguous with
      bone are larger, often occur in a paraspinal or epidural location, and can cause
      cord compression. Lesions noncontiguous with bone can be T2 hypointense. MRI
      helps in treatment planning.

PMID- 24660711
TI  - The imaging prevalence of osteolytic metastasis or multiple myeloma presenting as
      a periprosthetic lucency in the hip.
AB  - OBJECTIVE: The purpose of this article is to determine how often a malignant
      process presents as a lucency near a hip prosthesis, and to classify the
      frequency and distribution of differential diagnoses of these lytic lesions, and
      to determine their disposition. MATERIALS AND METHODS: Hip and pelvis imaging
      examinations obtained from January 1998 to June 2008 were text searched
      (1,164,560 reports) to identify patients with hip prostheses (3508 patients); the
      records were then searched and individually reviewed to identify periprosthetic
      lucency (2036 reports; 176 patients). The most likely cause for the lucency, as
      determined by the interpreting radiologist, was recorded. Malignancy was
      confirmed in all cases. Malignancy was excluded by biopsy for some patients but
      by clinical follow-up or at the time of revision, if performed, for most
      patients. Prevalence rates and 95% CIs were calculated. RESULTS: The overall
      prevalence of periprosthetic lucency was 5.02%. The prospective diagnoses
      suggested included loosening or infection (37.5%), degenerative cysts (19.3%),
      metastases (23.3%), multiple myeloma (14.8%), and metastasis of previously
      unknown malignancy (3.4%). The prevalence of metastases or multiple myeloma near
      a hip prosthesis was 1.54%; however, each of these patients had a known prior
      diagnosis of bone metastases, multiple myeloma, or primary bone malignancy.
      CONCLUSION: Among the 2036 examinations with periprosthetic lucency, there were
      no instances of new malignancy, metastasis, or myeloma. These results suggest
      that it is statistically unlikely that a lucency near a hip prosthesis represents
      the first presentation of malignancy or metastases, regardless of how large or
      aggressive it may appear on imaging.

PMID- 24660712
TI  - MRI of the thumb: anatomy and spectrum of findings in asymptomatic volunteers.
AB  - OBJECTIVE.:The purpose of this article is to analyze the MR anatomy and variable
      imaging characteristics of the thumb in asymptomatic volunteers. SUBJECTS AND
      METHODS: MRI of the thumb was obtained in 34 asymptomatic volunteers (mean age,
      33.9 +/- 9.2 years). Two radiologists independently assessed visibility and
      signal intensity (SI) and thickness of the following structures of the
      metacarpophalangeal and interphalangeal joints: proper and accessory radial and
      ulnar collateral ligaments, volar and dorsal plates, adductor pollicis
      aponeurosis, and annular pulleys. The presence and size of a synovial recess at
      the base of all plates was assessed. RESULTS: On intermediate-weighted fat
      saturated images, the ulnar collateral ligament of the metacarpophalangeal joint
      (reader 1, 79%; reader 2, 62%) and the adductor pollicis aponeurosis (reader 1,
      50%; reader 2, 82%) commonly had a striated appearance. The radial collateral
      ligament of both joints was mainly of low SI (metacarpophalangeal joint, 53% for
      reader 1 and 85% for reader 2; interphalangeal joint, 59% for reader 1 and 82%
      for reader 2). All four pulleys were visible in each volunteer. An intermediate
      SI was observed in almost all pulleys, whereas the variable annular pulley had
      predominantly a low SI (reader 1, 50%; reader 2, 74%). The ulnar collateral
      ligament of the metacarpophalangeal joint is typically less than 3 mm thick, and
      the radial collateral ligament is less than 2 mm thick. A full-thickness synovial
      recess at the base of the dorsal plate of the metacarpophalangeal joint was seen
      in almost all volunteers (reader 1, 97%; reader 2, 100%). CONCLUSION: The
      ligaments and pulleys of the thumb show considerable variability on MRI in
      healthy volunteers. The ulnar collateral ligament of the metacarpophalangeal
      joint is typically striated and less than 3 mm thick. A full-thickness synovial
      recess at the base of the dorsal plate of the metacarpophalangeal joint is a
      normal finding and should not be misdiagnosed as a tear.

PMID- 24660713
TI  - Imaging of musculoskeletal disorders related to pregnancy.
AB  - OBJECTIVE: This article provides an overview of the typical appearance of
      biomechanical and physiologic changes in pregnancy and an update on related
      pathophysiology. Conditions occurring during the childbearing, delivery and
      postpartum periods will be reported separately. CONCLUSION: Pregnancy causes
      biomechanical and physiologic changes that may be responsible for a wide spectrum
      of musculoskeletal disorders in the mother.

PMID- 24660714
TI  - MRI and MR angiography findings to differentiate jugular venous reflux from
      cavernous dural arteriovenous fistula.
AB  - OBJECTIVE: Both jugular venous reflux (JVR) and cavernous dural arteriovenous
      fistula (DAVF) manifest as abnormal venous signal intensities on time-of-flight
      (TOF) MR angiography (MRA). We investigated brain MRI and MRA findings that might
      differentiate JVR from cavernous DAVF. MATERIALS AND METHODS: Forty-one patients
      with abnormal venous signal intensities on TOF MRA in the cavernous sinus and its
      vicinity were selected from 1508 patients who had undergone TOF MRA over the
      previous 6 months. For comparison, the examinations of 26 patients with cavernous
      DAVF who had undergone imaging over the previous 8 years were collected. The
      following findings were assessed: the side and location of abnormal venous signal
      intensities on intracranial TOF MRA; the signal intensity of the proximal jugular
      vein on T2-weighted imaging; whether there was early opacification of the
      cavernous sinus in the arterial phase of contrast-enhanced MRA (CE-MRA); the side
      of jugular venous drainage in the arteriovenous phase of CE-MRA; and whether
      retrograde jugular venous flow was seen on neck TOF MRA. RESULTS: Abnormal venous
      signal intensities were seen on the left side in 73% of patients with JVR and 58%
      of patients with cavernous DAVF; involvement of the cavernous sinus was found in
      12% of patients with JVR and 100% of patients with cavernous DAVF. Increased
      signal intensity in the ipsilateral jugular vein on T2-weighted imaging was found
      in 73% of JVR patients and 4% of cavernous DAVF patients. Early opacification of
      the cavernous sinus in the arterial phase of CE-MRA, ipsilateral jugular venous
      drainage in the arteriovenous phase of CE-MRA, and ipsilateral retrograde jugular
      venous flow on neck TOF MRA were found in 0%, 0%, and 63%, respectively, of JVR
      patients and in 100%, 100%, and 0%, respectively, of cavernous DAVF patients.
      CONCLUSION: JVR and cavernous DAVF can be differentiated from one another using
      MRI and MRA.

PMID- 24660715
TI  - Differentiation between calcification and hemorrhage in brain tumors using
      susceptibility-weighted imaging: a pilot study.
AB  - OBJECTIVE: Our aim was to develop a robust method to differentiate calcification
      from hemorrhage in gliomas. Histopathologic examination was performed to validate
      hemorrhage and calcification. CONCLUSION: Phase images from eleven patients with
      glioma yielded statistically significant phase-shift values for calcification and
      hemorrhage compared with normal brain, whereas CT showed substantial overlap of
      Hounsfield units. Phase image analysis correctly differentiated between
      intratumoral calcification and hemorrhage in 86% of cases.

PMID- 24660716
TI  - Prognostic value of pretreatment 18F-FDG PET/CT parameters including visual
      evaluation in patients with head and neck squamous cell carcinoma.
AB  - OBJECTIVE: The purpose of this study was to determine whether pretreatment
      quantitative and visual parameters seen on PET/CT using (18)F-FDG add prognostic
      information for clinical staging in patients with head and neck cancer. MATERIALS
      AND METHODS: We enrolled 108 patients with histologically proven oral,
      oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who
      underwent FDG PET/CT before treatment and, later, definitive therapy in our
      study. PET/CT parameters-maximum standardized uptake value (SUVmax), metabolic
      tumor volume (MTV), total lesion glycolysis (TLG), and uptake pattern (sphere
      shaped or ring-shaped)-were recorded. The prognostic value of these parameters
      was evaluated using univariate and multivariate Cox regression analyses. RESULTS:
      In the univariate analysis, all of the FDG PET/CT parameters--SUVmax (> 10 g/mL)
      of the primary tumor, MTV (> 20 cm(3)), TLG (> 70 g), and uptake pattern (ring
      shaped)--were significantly associated with negative effects on disease-specific
      survival (DSS) and disease-free survival (DFS). In the multivariate analysis, the
      MTV and uptake pattern remained associated with DSS after corrections for the
      Union for International Cancer Control (UICC) stage and definitive therapy (p =
      0.023 and < 0.001, respectively). Another multivariate model that included MTV as
      a continuous variable, uptake pattern, and UICC stage showed that the uptake
      pattern remained significantly associated with DSS, whereas the association
      between DSS and MTV was not significant (p < 0.001 and = 0.332, respectively).
      CONCLUSION: Our data indicate that the pretreatment PET/CT parameters had
      prognostic value. In particular, a qualitative factor, uptake pattern, provided
      better prognostic information to the clinical staging of head and neck squamous
      cell carcinomas than the other PET/CT parameters.

PMID- 24660717
TI  - Is methylene diphosphonate bone scan necessary for initial staging of Ewing
      sarcoma if 18F-FDG PET/CT is performed?
AB  - OBJECTIVE: The purpose of this study was to determine whether methylene
      diphosphonate (MDP) bone scans are necessary during initial staging in patients
      with Ewing sarcoma (ES) in whom (18)F-FDG PET/CT is performed. MATERIALS AND
      METHODS: A retrospective review was performed of patients who underwent FDG
      PET/CT and MDP bone scan before treatment of newly diagnosed ES from January 2004
      to November 2012. Studies were reviewed to document suspected primary and
      metastatic malignancy. Pathology and imaging follow-up were used to determine the
      presence or absence of disease at suspected sites. RESULTS: Sixty patients were
      identified in whom FDG PET/CT and MDP bone scans were performed before treatment
      of newly diagnosed ES. Forty-four primary malignancies had a lytic CT appearance,
      three were sclerotic, and 13 involved only soft tissue. In 11 of 12 patients with
      osseous metastases, these were detected on PET/CT, with the one false-negative
      occurring in a sclerotic primary tumor; in nine of 12 patients with osseous
      metastases, these were detected on MDP bone scan, with the three false-negatives
      occurring in patients with lytic primary tumors. Only one of 13 patients with a
      soft-tissue primary malignancy had bone metastases on both bone scan and PET/CT.
      PET/CT also showed that eight patients had lung metastases and three patients had
      lymph node metastases, which were not evident on MDP bone scan. CONCLUSION: When
      ES is lytic, MDP bone scan does not add to staging performed by FDG PET/CT; thus,
      MDP bone scanning may be omitted. However, when ES is sclerotic, MDP bone scan
      may detect osseous metastases not detected by FDG PET/CT.

PMID- 24660718
TI  - Is the new ACR-SPR practice guideline for addition of oblique views of the ribs
      to the skeletal survey for child abuse justified?
AB  - OBJECTIVE: The purpose of our study was to determine whether adding oblique
      bilateral rib radiography to the skeletal survey for child abuse significantly
      increases detection of the number of rib fractures. MATERIALS AND METHODS: We
      identified all patients under 2 years old who underwent a skeletal survey for
      suspected child abuse from January 2003 through July 2011 and who had at least
      one rib fracture. These patients were age-matched with control subjects without
      fractures. Two randomized radiographic series of the ribs were performed, one
      containing two views (anteroposterior and lateral) and another with four views
      (added right and left oblique). Three fellowship-trained radiologists (two in
      pediatrics and one in trauma) blinded to original reports independently evaluated
      the series using a Likert scale of 1 (no fracture) to 5 (definite fracture). We
      analyzed the following: sensitivity and specificity of the two-view series for
      detection of any rib fracture and for location (using the four-view series as the
      reference standard), interobserver variability, and confidence level. RESULTS: We
      identified 212 patients (106 with one or more fractures and 106 without). The
      sensitivity and specificity of the two-view series were 81% and 91%,
      respectively. Sensitivity and specificity for detection of posterior rib
      fractures were 74% and 92%, respectively. There was good agreement between
      observers for detection of rib fractures in both series (average kappa values of
      0.70 and 0.78 for two-views and four-views, respectively). Confidence
      significantly increased for four-views. CONCLUSION: Adding bilateral oblique rib
      radiographs to the skeletal survey results in increased rib fracture detection
      and increased confidence of readers.

PMID- 24660719
TI  - Practice patterns for the use of iodinated i.v. contrast media for pediatric CT
      studies: a survey of the Society for Pediatric Radiology.
AB  - OBJECTIVE: There are limited data available on the use of i.v. contrast media for
      CT studies in the pediatric population. The purpose of this study is to determine
      the practice patterns of i.v. contrast media usage for pediatric CT by members of
      the Society for Pediatric Radiology (SPR). MATERIALS AND METHODS: SPR members
      were surveyed regarding the use of i.v. contrast media for pediatric CT studies.
      Questions pertained to information required before administering i.v. contrast
      media, types of central catheters for injecting i.v. contrast media, injection
      rates based on angiocatheter size and study type, and management of i.v. contrast
      media extravasation. RESULTS: The response rate of 6% (88/1545) represented
      practice patterns of 26% (401/1545) of the SPR membership. Most respondents
      thought the following clinical information was mandatory before i.v. contrast
      media administration: allergy to i.v. contrast media (97%), renal insufficiency
      (97%), current metformin use (72%), significant allergies (61%), diabetes (54%),
      and asthma (52%). Most administered i.v. contrast media through nonimplanted
      central venous catheters (78%), implanted venous ports (78%), and peripherally
      inserted central catheters (72%). The most common maximum i.v. contrast media
      injection rates were 5.0 mL/s or greater for a 16-gauge angiocatheter, 4.0 mL/s
      for an 18-gauge angiocatheter, 3.0 mL/s for a 20-gauge angiocatheter, and 2.0
      mL/s for a 22-gauge angiocatheter. For soft-tissue extravasation of i.v. contrast
      media, 95% elevate the affected extremity, 76% use ice, and 45% use heat.
      CONCLUSION: The results of this survey illustrate the collective opinion of a
      subset of SPR members relating to the use of i.v. contrast media in pediatric CT,
      providing guidelines for clinical histories needed before i.v. contrast media,
      maximum i.v. contrast injection rates for standard angiocatheters, contrast media
      injection rates for specific CT studies, and management of i.v. contrast media
      soft-tissue extravasation.

PMID- 24660720
TI  - Metallic stent placement for the management of tracheal carina strictures and
      fistulas: technical and clinical outcomes.
AB  - OBJECTIVE: The purpose of this article is to assess the technical and clinical
      outcomes of metallic stent placement in strictures and fistulas involving the
      carina. MATERIAL AND METHODS: We performed a retrospective analysis of patients
      who had undergone stenting for disease involving the carina. We initially
      reviewed the symptoms, underlying causes, and the types of stent configuration
      used. We also assessed the technical success rate of stenting, its effectiveness
      in achieving symptomatic relief, the incidence of stent-related complications,
      and stent patency. RESULTS: Thirty-two stenting procedures were performed in 23
      patients (mean age, 56.3 years) for the treatment of strictures (n = 21), an
      esophagorespiratory fistula (n = 1), or both (n = 1) present in the carina. Three
      cases were associated with benign causes, whereas 20 were related to
      malignancies. Dyspnea was the most common symptom (n = 22). We placed metallic
      stents in four different configurations, among which placement in juxtacarinal
      segments was the most common configuration (n = 23). Technical success was
      achieved in 96.9% of cases, and symptomatic improvement was observed in 90.6% of
      cases. Stent-related complications were observed after 10 procedures (31.3%).
      Stent obstruction occurred in seven patients (21.9% of procedures), most commonly
      because of tumor progression. The mean follow-up period was 83.1 days, during
      which time 15 patients died as a result of disease progression, five were
      discharged without hope for improvement, two were discharged without symptomatic
      recurrence, and one was lost to follow-up. CONCLUSION: Airway stenting can be
      performed in the carina with high technical success using variable stent
      configurations. Although the rate of immediate symptomatic improvement is high,
      stent-related complications frequently occur.

PMID- 24660721
TI  - Evaluating peripheral arterial disease with unenhanced quiescent-interval single
      shot MR angiography at 3 T.
AB  - OBJECTIVE: The objective of our study was to assess the diagnostic performance of
      quiescent-interval single-shot (QISS) MR angiography (MRA) at 3 T for the
      evaluation of chronic lower limb ischemia. SUBJECTS AND METHODS: For this
      prospective study, 25 patients referred for lower extremity angiography for
      suspected or known chronic peripheral arterial disease were imaged on a 3-T
      system using QISS MRA. Contrast-enhanced MRA of the lower extremities was
      acquired at 3 T for each patient at the time of the initial visit and served as
      the noninvasive reference standard. Two blinded reviewers separately graded the
      degree of arterial stenosis. The sensitivity and specificity of QISS MRA for the
      determination of significant (>= 50%) stenosis were calculated against contrast
      enhanced MRA. Subsequent selective digital subtraction angiography (DSA) was
      performed and reviewed in nine patients. RESULTS: QISS MRA exhibited diagnostic
      performance nearly equivalent to that of contrast-enhanced MRA and also showed
      strong correlation with findings on DSA. Segment-based analysis revealed that,
      for the two reviewers, QISS MRA had sensitivities of 95.9% (142 of 148 segments)
      and 93.5% (145 of 155 segments) and specificities of 98.5% (595 of 604 segments)
      and 97.0% (578 of 596 segments) on comparison with contrast-enhanced MRA.
      CONCLUSION: QISS MRA maintains high diagnostic performance at 3 T despite the
      challenges inherent to image acquisition at higher field strengths.

PMID- 24660722
TI  - ABLATE: a renal ablation planning algorithm.
AB  - OBJECTIVE: The purpose of this article is to present the ABLATE renal ablation
      planning algorithm (Table 1), which is based on anatomic renal tumor
      characteristics critical to ablation. [Table: see text]. CONCLUSION: ABLATE
      provides a systematic method for reviewing cross-sectional imaging of renal
      masses for ablation planning purposes. The goal of this system is to help
      proceduralists anticipate and manage potential technical challenges of renal
      ablations to maximize oncologic outcomes and minimize complications.

PMID- 24660723
TI  - Beyond ultrasound: CT and MRI of ectopic pregnancy.
AB  - OBJECTIVE: Although ultrasound is the primary modality used in the diagnosis of
      ectopic pregnancy, various forms of this condition and their complications may
      occasionally be further evaluated with MRI or may be incidentally detected on CT
      or MRI when an alternative diagnosis is suspected. CONCLUSION: Various types of
      ectopic pregnancy have characteristic imaging features. Radiologists should be
      familiar with these features and should always consider the possibility of
      ectopic pregnancy in the setting of hemoperitoneum or a pelvic mass in a woman of
      child-bearing age. Familiarity with the typical CT and MRI appearances of various
      forms of ectopic pregnancy facilitates prompt and accurate diagnosis and
      treatment.

PMID- 24660724
TI  - Smaller reduction in 3D breast density associated with subsequent cancer
      recurrence in patients with breast cancer receiving adjuvant tamoxifen therapy.
AB  - OBJECTIVE: The purpose of this study was to retrospectively investigate whether
      3D breast density changes measured using MRI were associated with recurrent
      cancer in patients with breast cancer who received adjuvant tamoxifen. MATERIALS
      AND METHODS: A search of the breast MRI database (2007-2008) revealed a dataset
      that included 80 women (mean age, 44 years; range, 27-68 years) with breast
      cancer who underwent breast-conserving surgery, adjuvant tamoxifen treatment, and
      breast MRI before and after tamoxifen. The following clinicopathologic variables
      were collected: age, body mass index, menopausal status, family history, tumor
      stage, tumor grade, hormonal receptor status, and adjuvant chemotherapy status.
      MRI variables (total breast volume, fibro-glandular volume, and breast density)
      were measured for the contralateral untreated breast before and after tamoxifen
      treatment, and the percentage changes were recorded. A multivariate logistic
      regression analysis was performed to identify independent factors that were
      associated with cancer recurrence. RESULTS: Overall, 12 (15%) of the 80 women
      developed recurrence. No recurrent cancers were found in the remaining 68
      patients (85%) at a median follow-up of 48 months (range, 37-60 months).
      Percentage reduction of breast density after tamoxifen was the only independent
      factor associated with recurrence (adjusted odds ratio [OR] = 0.848, 95% CI =
      0.769-0.935, and p = 0.001 for observer 1; adjusted OR = 0.957, 95% CI = 0.919
      0.996, and p = 0.032 for observer 2) in the multivariate analysis. CONCLUSION:
      Three-dimensional breast density changes measured using MRI during tamoxifen
      treatment were an independent factor associated with cancer recurrence in
      patients with breast cancer who received adjuvant tamoxifen.

PMID- 24660725
TI  - Patient compliance and diagnostic yield of 18-month unilateral follow-up in
      surveillance of probably benign mammographic lesions.
AB  - OBJECTIVE: The purpose of this study is to determine the patient compliance with
      and diagnostic yield of 18-month unilateral mammography in surveillance of
      probably benign (BI-RADS category 3) lesions. MATERIALS AND METHODS: This
      retrospective study identified lesions prospectively classified BI-RADS 3 in
      asymptomatic women from January 1, 2004, to December 31, 2008. Surveillance
      protocol for BI-RADS 3 lesions included 6-month (unilateral), 12-month
      (bilateral), 18-month (unilateral), and 24-month (bilateral) imaging, with
      subsequent annual screening. Demographics, surveillance data, BI-RADS upgrades
      and downgrades, and biopsy results were abstracted from the longitudinal medical
      record. RESULTS: One thousand one hundred eighty-eight lesions in 1077 patients
      (mean age, 51.5 years; age range, 26-89 years) had BI-RADS 3 assessment,
      representing 1.07% of all screening examinations. The compliance rates for follow
      up at 6, 12, 18, and 24 months were 83.3%, 75.9%, 54.8%, and 53.9%, respectively.
      Sixty lesions were upgraded to BI-RADS 4 or 5 during surveillance. Biopsy
      revealed 15 cancers (cancer yield of 1.47%) from 1017 lesions with either 24
      month imaging stability or tissue diagnosis available. Five, six, one, and three
      cancers were detected at 6, 12, 18, and 24 months, respectively. Cancers were all
      stage 0 or 1 except for one stage 2A cancer. Seven hundred forty-four of 1188
      (62.6%) BI-RADS 3 lesions were downgraded before completing 2-year surveillance.
      CONCLUSION: Most (11/15 [73%]) breast cancers initially assessed as BI-RADS 3 are
      diagnosed at up to 12 months' surveillance. Eighteen-month unilateral mammography
      performed as BI-RADS 3 surveillance contributes minimally to cancer detection and
      has poor patient compliance.

PMID- 24660726
TI  - Comparison of breast cancers diagnosed in screening patients in their 40s with
      and without family history of breast cancer in a community outpatient facility.
AB  - OBJECTIVE: The purpose of this study was to compare invasive breast cancer in
      patients in their 40s with and without a family history of breast cancer as well
      as the lymph node meta-static rate and mastectomy rate. MATERIALS AND METHODS:
      From 2000 to 2011, a total of 793,827 examinations were performed; 221,541 (28%)
      were women between 40 and 49 years old. A total of 6965 cancers were found in
      6511 patients. Specifically, 1207 cancers (17.3%) were detected in 1162 patients
      in their 40s. Patients presenting for diagnostic evaluation and those with a
      personal history of breast cancer were excluded, leaving 388 cancers available
      for study; 238 (61%) cancers were in patients with no family history of breast
      cancer, and 150 (39%) were in patients with a family history of breast cancer.
      Pearson chi-square, Fisher exact, and Student t tests were used for between-group
      comparisons for qualitative data. A two-sided p value was reported for all tests.
      RESULTS: The difference in lesions detected by imaging was not statistically
      significant (p = 0.17); 65% (154/238) had invasive and 35% (84/238) noninvasive
      disease in the no family history of breast cancer group and 65% (98/150) and 35%
      (52/150), respectively, in the family history of breast cancer group (p = 0.90).
      The mastectomy rate was not statistically significantly different (p = 0.14).
      Fifteen percent (35/238) of the no family history of breast cancer patients and
      12% (18/150) of the family history of breast cancer patients had positive lymph
      nodes (p = 0.45). CONCLUSION: In patients in their 40s with or without a family
      history of breast cancer, no differences were detected in the proportion of
      invasive versus noninvasive cancers diagnosed, lymph node metastases, or
      mastectomy rates. Screening mammography should be performed in this age group
      regardless of family history.

PMID- 24660728
TI  - Congenital abnormalities of the pulmonary arteries in adults.

PMID- 24660729
TI  - Applications of dual-energy CT in emergency radiology.
AB  - OBJECTIVE: Recent technologic advances in MDCT have led to the introduction of
      dual-energy CT (DECT). The basic principle of DECT is to acquire images at two
      different energy levels simultaneously and to use the attenuation differences at
      these different energy levels for deriving additional information, such as
      virtual monochromatic images, artifact suppression, and material composition of
      various tissues. CONCLUSION: A variety of image reconstruction and postprocessing
      techniques are available for better demonstration and characterization of
      pathologic abnormalities. DECT can provide both anatomic and functional
      information of different organ systems. This article focuses on the main
      applications of DECT in emergency radiology.

PMID- 24660730
TI  - Times have changed! Forensic radiology--a new challenge for radiology and
      forensic pathology.
AB  - OBJECTIVE: The ongoing development of imaging and the recent integration of cross
      sectional imaging methods into the medicolegal workflow have resulted in an
      increasing number of forensic institutes acquiring dedicated CT and MRI scanners.
      The purpose of this article is to evaluate the different aspects of postmortem
      imaging and to detail the necessary cooperation between radiologists and forensic
      pathologists for mutual learning and accurate science to form a new subspecialty:
      forensic radiology. CONCLUSION; Forensic radiology must integrate the expertise
      of forensic pathologists and radiologists. The challenge is to unite these two
      disciplines first by direct and intense communications and second by a basic
      understanding of forensic pathology by radiologists as well as a foundational
      knowledge of postmortem imaging by forensic pathologists, in combination with the
      establishment of educational and reporting guidelines.

PMID- 24660731
TI  - Patient skin reactions from interventional fluoroscopy procedures.
AB  - OBJECTIVE: This article presents relevant physics, technology, and radiobiology
      along with a summary of operational guidelines for radiation management in
      interventional fluoroscopy procedures. CONCLUSION: Fluoroscopically guided
      interventional procedures offer patients clinical and economic benefits as
      compared with the alternatives. Radiation-induced skin injuries are uncommon but
      continue to occur.

PMID- 24660732
TI  - Radiographic features of potential donor livers that precluded donation.
AB  - OBJECTIVE: The objective of our study was to catalog the anatomic features shown
      on preoperative CT that precluded living-donor liver donation. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 159 consecutive candidates
      who were evaluated for potential right or left lobe liver donation from November
      2007 to January 2012 using MDCT angiography and cholangiography. For the
      potential donors who were excluded secondary to findings depicted on preoperative
      imaging, we determined which findings precluded donation. RESULTS: In two (1%)
      patients who had no prohibitive preoperative imaging findings, anatomic
      abnormalities were detected intraoperatively that precluded transplantation.
      Sixty-one (38%) candidates were excluded from liver donation on the basis of
      imaging findings. Of these patients, 40 (66%) had inadequate liver volume, 14
      (23%) had vascular or biliary variants, five (8%) had steatosis, and two (3%)
      were found to have renal cell carcinoma. Arterial and biliary variants were the
      most common reason for exclusion based on anatomic findings. CONCLUSION:
      Inadequate liver volume was the most common reason for exclusion based on
      preoperative imaging. Arterial and biliary anatomic variants precluded both right
      and left lobe transplantation in a number of cases.

PMID- 24660733
TI  - Subtraction color map of contrast-enhanced and unenhanced CT for the prediction
      of pancreatic necrosis in early stage of acute pancreatitis.
AB  - OBJECTIVE: The objective of our study was to evaluate the accuracy of subtraction
      color-map images created from contrast-enhanced CT (CECT) and unenhanced CT for
      the diagnosis of pancreatic necrosis in the early stage of acute pancreatitis.
      MATERIALS AND METHODS: Forty-eight patients underwent unenhanced CT and CECT
      within 72 hours from the onset of acute pancreatitis. Subtraction color-map
      images were created from unenhanced CT and CECT using a 3D nonrigid registration
      method. Three radiologists reviewed two image sets: CECT alone and subtraction
      color-map images in conjunction with CECT. Readers evaluated each image set for
      the presence of pancreatic necrosis. The reference standard for pancreatic
      necrosis was CT or MRI 1 week or more after the onset of acute pancreatitis. The
      performance of each image set for the prediction of pancreatic necrosis was
      calculated and compared using the McNemar test. RESULTS: Eleven of the 48
      patients developed pancreatic necrosis. There were no technical failures creating
      the subtraction images. The sensitivity, specificity, and accuracy for predicting
      pancreatic necrosis with CECT were 64%, 97%, and 90%, respectively, for reader 1;
      73%, 87%, and 83% for reader 2; and 73%, 87%, and 83% for reader 3. The
      sensitivity, specificity, and accuracy for predicting pancreatic necrosis with
      the subtraction color maps were 100%, 100%, and 100%, respectively, for reader 1;
      100%, 95%, and 96% for reader 2; and 82%, 92%, and 90% for reader 3. Accuracy
      significantly improved with the addition of subtraction color maps compared with
      CECT alone for reader 1 (p = 0.03) and reader 2 (p = 0.02) but not for reader 3
      (p = 0.37). CONCLUSION: A subtraction color map is accurate in the diagnosis of
      pancreatic necrosis in the early stage of acute pancreatitis.

PMID- 24660734
TI  - Diagnosis of urothelial tumors with a dedicated dual-source dual-energy MDCT
      protocol: preliminary results.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance
      of a dedicated dual-source dual-energy MDCT (DECT) protocol for the detection of
      urothelial tumors. MATERIALS AND METHODS: A DECT protocol including furosemide
      and split-bolus contrast injection was used in 69 consecutive patients with
      suspected abnormalities of the urinary system. Thirteen patients were excluded
      because there was no follow-up available. In 56 patients, the final diagnosis was
      proven with endoscopy, biopsy, or follow-up and included urothelial tumors (n =
      37) in 16 patients, other urinary tract pathologies (n = 9) in eight patients,
      and absence of lesions of the collecting system in 32 patients. The image series
      consisted of a dual-energy true unenhanced series, 35-second arterial phase, and
      8-minute nephrographic-excretory phase and were analyzed retrospectively. True
      enhancement of all detected lesions was measured. On the basis of the DECT data
      of the contrast-enhanced images, virtual unenhanced series were created and
      iodine concentration was calculated using commercially available software. The
      attenuation difference between virtual unenhanced and contrast-enhanced images
      (virtual enhancement) was measured. CT findings were compared with the final
      diagnosis. RESULTS: Urothelial tumors were identified on 35-second series, 8
      minute series, and both series combined, with sensitivity of 91.9% (95% CI, 78.1
      98.2%), 83.4% (68.0-93.8%), and 97.3% (85.8-100%), respectively. Urothelial
      tumors showed stronger virtual enhancement (p = 0.02) and higher iodine
      concentration (p = 0.03) than lesions of other origin. Distinction between
      urothelial tumors and nontumoral lesions was possible with sensitivity of 91.9%
      (78.1-98.2%) when using a threshold concentration of at least 1.0 mg I/mL.
      CONCLUSION: Dual phase DECT with virtual unenhanced imaging and iodine
      concentration measurement appears to be a useful diagnostic test for urothelial
      tumors.

PMID- 24660735
TI  - Biostatistics primer for the radiologist.
AB  - OBJECTIVE: The purpose of this article is to review the most common data analysis
      methods encountered in radiology-based studies. Initially, description of
      variable types and their corresponding summary measures are provided; subsequent
      discussion focuses on comparison of these summary measures between groups, with a
      particular emphasis on regression analysis. CONCLUSION: Knowledge of statistical
      applications is critical for radiologists to accurately evaluate the current
      literature and to conduct scientifically rigorous studies. Misapplication of
      statistical methods can lead to inappropriate conclusions and clinical
      recommendations.

PMID- 24660736
TI  - Rotator cuff tendon ultrastructure assessment with reduced-orientation dipolar
      anisotropy fiber imaging.
AB  - OBJECTIVE: The anisotropic fibrous structure of collagen can significantly affect
      MRI signal intensity. Use of this magic angle effect as a contrast mechanism has
      been previously termed "dipolar anisotropy fiber imaging." The goal of this pilot
      study was to use a reduced-orientation version of dipolar anisotropy fiber
      imaging to study rotator cuff tendon internal fiber structure. CONCLUSION: The
      reduced-orientation dipolar anisotropy fiber imaging technique can be used to
      delineate the complex contributions and ultrastructure of the rotator cuff.

PMID- 24660737
TI  - Diagnostic accuracy of sonoelastography in detecting malignant thyroid nodules: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this systematic review was to determine the diagnostic
      accuracy of sonoelastography in detecting malignant thyroid nodules. MATERIALS
      AND METHODS: A systematic search in MEDLINE and bibliographic databases was
      performed for the terms "thyroid nodule" and "sonoelastography." The inclusion
      criteria were the report of a 4- or 5-point scoring scale for elasticity score by
      qualitative sonoelastography as the index test and fine-needle aspiration (FNA)
      cytology or histopathology for thyroid nodules as the reference standard. Studies
      in which only the strain ratio was reported and studies of patients with
      underlying medical conditions were excluded. The methodologic quality of the
      studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies
      (QUADAS) tool. A meta-analysis of diagnostic accuracy measures for
      sonoelastography was performed using Meta-DiSc freeware software (version 1.4).
      RESULTS: A total of 12 studies assessing 1180 thyroid nodules (817 benign and 363
      malignant) were included. The most commonly used threshold for characterizing
      malignancy--that is, elasticity scores between 2 and 3--showed a sensitivity of
      86.0% (95% CI, 81.9-89.4%) and specificity of 66.7% (95% CI, 63.4-69.9%) with
      positive and negative likelihood ratios and a diagnostic odds ratio of 3.82 (95%
      CI, 2.38-6.13), 0.16 (95% CI, 0.08-0.32), and 27.51 (95% CI, 9.21-82.18),
      respectively. The highest sensitivity of the test was achieved by a threshold
      elasticity score of between 1 and 2 with a sensitivity of 98.3% (95% CI, 96.2
      99.5%). CONCLUSION: Sonoelastography can be considered as a reliable screening
      tool for characterizing thyroid nodules. An elasticity score of 1 is indicative
      of benign pathology in almost all cases and can be used to exclude many patients
      from further invasive assessments.

PMID- 24660738
TI  - Breast emergencies: types, imaging features, and management.
AB  - OBJECTIVE: The objective of this article is to describe the types of breast
      emergencies that can be encountered in a breast imaging practice, discuss the
      characteristic imaging features of these emergencies, and explain the most common
      methods and interventions used for the treatment of breast emergencies and
      complications. CONCLUSION: Breast emergencies are uncommon but require prompt
      identification and management when they do occur. Patients with mastitis or a
      breast abscess may be seen for either diagnosis or treatment. Most complications
      are the result of interventional procedures. Pseudoaneurysms, postbiopsy
      hematoma, and localization wire migration are the most common situations
      encountered. A milk fistula resulting from a core biopsy is uncommon.
      Fortunately, seat-belt injuries to the breast are rare. Knowledge of these
      entities--of the usual presentation, management, and appropriate follow-up
      protocols--is essential for breast imagers.

PMID- 24660739
TI  - Efficacy of sonazoid (perflubutane) for contrast-enhanced ultrasound in the
      differentiation of focal breast lesions: phase 3 multicenter clinical trial.
AB  - OBJECTIVE: The objective of our study was to compare the efficacy of contrast
      enhanced ultrasound (CEUS) using the ultrasound contrast agent Sonazoid
      (perflubutane) with unenhanced ultrasound and supplementary contrast-enhanced MRI
      in the differential diagnosis (benign vs malignant) of focal breast lesions. The
      safety of Sonazoid was also assessed in this study. SUBJECTS AND METHODS: A total
      of 127 patients with focal breast lesions were enrolled in this study at five
      centers in Japan. Three reviewers who were blinded to the patient characteristics
      independently assessed the ultrasound images and MR images in a randomized
      sequence. The accuracy, sensitivity, and specificity of CEUS, unenhanced
      ultrasound, and supplementary contrast-enhanced MRI for the differential
      diagnosis were compared using generalized estimating equation analyses.
      Diagnostic confidence was also assessed. RESULTS: The accuracy of CEUS was
      significantly higher than that of unenhanced ultrasound (87.2% vs 65.5%,
      respectively; p < 0.001). In addition, CEUS showed significantly higher
      specificity, although the improvement in sensitivity was not statistically
      significant. The accuracy and specificity were significantly higher with CEUS
      than with contrast-enhanced MRI, but the improvement in sensitivity was not
      statistically significant. The area under the curve in a receiver operating
      characteristic analysis was significantly greater with CEUS than with unenhanced
      ultrasound. The incidence of adverse events was 11.4% and the incidence of
      adverse drug reactions was 3.3%. All adverse drug reactions were mild.
      CONCLUSION: CEUS using Sonazoid was confirmed to be superior to unenhanced
      ultrasound for the differential diagnosis (benign vs malignant) of focal breast
      lesions in terms of diagnostic accuracy with no serious adverse reactions.

PMID- 24660740
TI  - Neuroimaging evaluation of sports-related concussion.

PMID- 24660741
TI  - Combined CT examinations: should they be interpreted by the same radiologist or
      split?

PMID- 24660742
TI  - No increased risk of cancer from CT.

PMID- 24660743
TI  - Extracardiac findings in cardiac CT.

PMID- 24660744
TI  - Reply: To PMID 23971446.

PMID- 24660745
TI  - Conclusion of increased risk of cataracts associated with CT studies of the head
      may not be justified.

PMID- 24660746
TI  - Reply: To PMID 23971456.

PMID- 24660747
TI  - Single molecule visualization and characterization of Sox2-Pax6 complex formation
      on a regulatory DNA element using a DNA origami frame.
AB  - We report the use of atomic force microscopy (AFM) to study Sox2-Pax6 complex
      formation on the regulatory DNA element at a single molecule level. Using an
      origami DNA scaffold containing two DNA strands with different levels of tensile
      force, we confirmed that DNA bending is necessary for Sox2 binding. We also
      demonstrated that two transcription factors bind cooperatively by observing the
      increased occupancy of Sox2-Pax6 on the DNA element compared to that of Sox2
      alone. 

PMID- 24660748
TI  - Unravelling a vicious circle: animal feed marketed in Costa Rica contains
      irregular concentrations of tetracyclines and abundant oxytetracycline-resistant
      Gram-positive bacteria.
AB  - Diverse tetracyclines are used to prevent and control bacterial infections in
      livestock and farmed fish. These drugs are administered through the diet, but
      farmers seldom check whether feed contains antibiotic-resistant bacteria that may
      colonise their crops or transfer their resistance traits to species of veterinary
      relevance. To examine whether antibiotic dosage defines the abundance of
      antibiotic-resistant bacteria in animal feed, we determined the concentration of
      parental compounds and epimers of oxytetracycline (OTC), doxycycline,
      tetracycline and chlortetracycline, as well as the abundance and resistance level
      of OTC-resistant bacteria in samples of fish (n = 21), poultry (n = 21), swine (n
      = 21), and shrimp feed (n = 21) marketed in Costa Rica. Fish feed contained the
      highest amounts of tetracyclines (119-8365 mg kg(-1)) and the largest proportion
      of bacteria resistant to 10 MUg ml(-1) (1.8-92.4%) or 100 MUg ml(-1) of OTC (12.5
      63.8%). Poultry (78-438 mg kg(-1)) and swine (41-1076 mg kg(-1)) feed had
      intermediate concentrations of tetracyclines and OTC-resistant bacteria (0.2-66%
      and 0.3-49%, respectively), whereas shrimp feed showed the lowest amounts of
      tetracyclines (21.5-50.3 mg kg(-1)), no OTC and no culturable OTC-resistant
      bacteria. In line with these results, the MIC50 of OTC for 150 isolates from fish
      and poultry feed was > 256 ug ml(-1), while that of 150 bacteria isolated from
      swine feed was 192 ug ml(-1). Phenotypic tests, fatty acid profiles and
      proteotypic analyses by matrix-assisted laser desorption/ionisation-time of
      flight mass-spectroscopy revealed that most OTC-resistant isolates were Gram
      positive bacteria of low G+C% content from the genera Staphylococcus and
      Bacillus. Clear correlations between OTC dosage and feed colonisation with OTC
      resistant bacteria were seen in medicated feed for fish (r = 0.179-0.651).
      Nonetheless, some unmedicated feed for fish, swine and poultry contained large
      populations of OTC-resistant bacteria, suggesting that raw materials and
      manufacturing processes may also influence carriage of OTC-resistant bacteria in
      animal feed.

PMID- 24660749
TI  - Cerebrospinal fluid gusher in cochlear implantation.
AB  - OBJECTIVES: To share our experience of cerebrospinal fluid (CSF) gusher in
      cochlear implantation. METHODS: Demographic, radiological, and surgical results
      of patients with CSF gusher in 523 consecutive cochlear implant recipients
      including children and adults as well as our management technique were evaluated
      and a review of the literature has been included. RESULTS: Fifteen (2.87%) cases
      had CSF gusher. Two patients (13.3%) were adults with post-lingual hearing loss
      and the rest 12 (86.7%) were children with congenital hearing loss. Twelve
      patients (80%) had various types of inner ear malformation. Three patients (20%)
      had no predictable risk of CSF gusher from history or pre-operative imaging. In
      all patients, CSF gushers were controlled with our technique of packing the
      electrode entrance site with no additional measures. CONCLUSION: CSF gusher may
      occur with post-lingual hearing loss and in children with apparently unremarkable
      imaging and history. Thus, surgeons should always be ready to manage it.
      Management of CSF gusher can be mainly performed during the initial surgery by
      precise tight packing of the electrode entrance site. Furthermore, non-surgical
      or surgical measures are rarely required to stop a persistent leak. Our results
      show that our management technique may be recommended as well.

PMID- 24660750
TI  - Ophthalmic artery microcatheterization for research purposes in pigs. A technical
      note.
AB  - PURPOSE: To describe a technique for micro catheterization of the external
      ophthalmic artery (EO) in pigs for investigational and training purposes.
      METHODS: Carotid angiography was performed in seven male domestic pigs. The
      external ophthalmic artery was reached with a microcatheter in order to
      administer a neoplastic drug in the eye. RESULTS: The external ophthalmic artery
      could be found arising from the infraorbital (IO) artery in the bend of the
      internal maxillary (IM) artery. It could be reached in every animal. CONCLUSION:
      Following anatomic landmarks of the external carotid (EC) artery the ophthalmic
      artery can be easily reached and catheterized for training and investigational
      purposes.

PMID- 24660751
TI  - In utero lung gene transfer using adeno-associated viral and lentiviral vectors
      in mice.
AB  - Virus-mediated gene transfer to the fetal lung epithelium holds considerable
      promise for the therapeutic management of prenatally diagnosed, potentially life
      threatening inherited lung diseases. In this study we hypothesized that efficient
      and life-long lung transduction can be achieved by in utero gene therapy, using
      viral vectors. To facilitate diffuse entry into the lung, viral vector was
      injected into the amniotic sac of C57BL/6 mice on embryonic day 16 (term, ~ 20
      days) in a volume of 10 MUl. Vectors investigated included those based on adeno
      associated virus (AAV) (serotypes 5, 6.2, 9, rh.64R1) and vesicular stomatitis
      virus G glycoprotein (VSV-G)-pseudotyped HIV-1-based lentivirus (LV). All vectors
      expressed green fluorescent protein (GFP) under the transcriptional control of
      various promoters including chicken beta-actin (CB) or cytomegalovirus (CMV) for
      AAV and CMV or MND (myeloproliferative sarcoma virus enhancer, negative control
      region deleted) for LV. Pulmonary GFP gene expression was detected by
      fluorescence stereoscopic microscopy and immunohistochemistry for up to 9 months
      after birth. At equivalent vector doses (mean, 12 * 10(10) genome copies per
      fetus) three AAV vectors resulted in long-term (up to 9 months) pulmonary
      epithelium transduction. AAV2/6.2 transduced predominantly cells of the
      conducting airway epithelium, although transduction decreased 2 months after
      vector delivery. AAV2/9-transduced cells of the alveolar epithelium with a type 1
      pneumocyte phenotype for up to 6 months. Although minimal levels of GFP
      expression were observed with AAV2/5 up to 9 months, the transduced cells
      immunostained positive for F480 and were retrievable by bronchoalveolar lavage,
      confirming an alveolar macrophage phenotype. No GFP expression was observed in
      lung epithelial cells after AAV2/rh.64R1 and VSV-G-LV vector-mediated gene
      transfer. We conclude that these experiments demonstrate that prenatal lung gene
      transfer with AAV vectors engineered to target pulmonary epithelial cells may
      provide sustained long-term levels of transgene expression, supporting the
      therapeutic potential of prenatal gene transfer for the treatment of congenital
      lung diseases.

PMID- 24660752
TI  - Non-canonical 3'-5' extension of RNA with prebiotically plausible ribonucleoside
      2',3'-cyclic phosphates.
AB  - Ribonucleoside 2',3'-cyclic phosphates (N>p's) are generated by multiple
      prebiotically plausible processes and are credible building blocks for the
      assembly of early RNA oligomers. While N>p's can be polymerized into short RNAs
      by non-enzymatic processes with variable efficiency and regioselectivity, no
      enzymatic route for RNA synthesis had been described. Here we report such a non
      canonical 3'-5' nucleotidyl transferase activity. We engineered a variant of the
      hairpin ribozyme to catalyze addition of all four N>p's (2',3'-cyclic A-, G-, U-,
      and CMP) to the 5'-hydroxyl termini of RNA strands with 5' nucleotide addition
      enhanced in all cases by eutectic ice phase formation at -7  degrees C. We also
      observed 5' addition of 2',3'-cyclic phosphate-activated beta-nicotinamide
      adenine dinucleotide (NAD>p) and ACA>p RNA trinucleotide, and multiple additions
      of GUCCA>p RNA pentamers. Our results establish a new mode of RNA 3'-5' extension
      with implications for RNA oligomer synthesis from prebiotic nucleotide pools. 

PMID- 24660753
TI  - Antimicrobial activities of novel mannosyl lipids isolated from the biocontrol
      fungus Simplicillium lamellicola BCP against phytopathogenic bacteria.
AB  - The antagonistic fungus Simplicillium lamellicola BCP has been developed as a
      microbial biopesticide that effectively controls the development of various plant
      diseases caused by both pathogenic bacteria and pathogenic fungi. Antibacterial
      bioassay-directed fractionation was used to isolate mannosyl lipids from S.
      lamellicola BCP, and the structures of these compounds were elucidated using
      spectral analysis and chemical degradation. Three novel mannosyl lipids were
      characterized and identified as halymecins F and G and (3R,5R)-3-O-beta-D
      mannosyl-3,5-dihydrodecanoic acid. Massoia lactone and (3R, 5R)-3-hydroxydecan-5
      olide were also isolated from S. lamellicola BCP. The three novel compounds
      inhibited the growth of the majority of phytopathogenic bacteria that were
      tested, and halymecin F displayed the strongest antibacterial activity.
      Agrobacterium tumefaciens was the most sensitive to the three novel compounds,
      with IC50 values ranging from 1.58 to 24.8 MUg/mL. The ethyl acetate extract of
      the fermentation broth from the antagonistic fungus effectively reduced the
      bacterial wilt caused by Ralstonia solanacearum on tomato seedlings. These
      results indicate that S. lamellicola BCP suppresses the development of plant
      bacterial diseases through the production of antibacterial metabolites.

PMID- 24660754
TI  - Polypyrrole-coated chainlike gold nanoparticle architectures with the 808 nm
      photothermal transduction efficiency up to 70%.
AB  - Aqueous Au nanoparticles (NPs) are employed as the building blocks to construct
      chainlike self-assembly architectures, which greatly enhance the photothermal
      performance at 808 nm. Biocompatible polypyrrole (PPy) is further adopted as the
      package material to coat Au NP chains, producing stable photothermal agents. As a
      result of contributions from chainlike Au, the PPy shell, as well as the Au-PPy
      composite structures, the capability of photothermal transduction at 808 nm is
      greatly enhanced, represented by the high photothermal transduction efficiency up
      to 70%. Primary animal experiment proves that the current composite photothermal
      agents are efficient in inhibiting tumor growth under an 808 nm irradiation,
      showing the potentials for in vivo photothermal therapy. 

PMID- 24660755
TI  - Apoptosis signal-regulating kinase 1 as a therapeutic target.
AB  - INTRODUCTION: All organisms are ordinarily exposed to various stresses. It is
      important for organisms to possess appropriate stress response mechanisms and to
      maintain homeostasis because the disruption of a stress response system can cause
      various diseases. Apoptosis signal-regulating kinase 1 (ASK1) is one of the
      stress-responsive MAP3Ks. ASK1 plays an important role in the response to
      reactive oxygen species (ROS), endoplasmic reticulum stress and pro-inflammatory
      cytokines, and it is involved in the pathogenesis of various diseases. AREAS
      COVERED: In this review, the authors describe recent literature concerning the
      intricate and elaborate regulation system of ASK1, the function of ASK1 during a
      cellular stress response and the involvement of ASK1 in many diseases, including
      cancer, neurodegenerative diseases, infections, diabetes and cardiovascular
      diseases. EXPERT OPINION: In certain disease conditions, ASK1 plays a protective
      role, whereas ASK1 can exacerbate the pathology of other diseases. Although ASK1
      is involved in various diseases, there is no therapy or drug that targets ASK1
      for use in a clinical setting. Recently, ASK1 inhibitors (K811 and MSC2032964A)
      have emerged, and their therapeutic potentials have been tested in vivo. ASK1 is
      currently receiving considerable attention as a new therapeutic target.

PMID- 24660756
TI  - Few-layer MoS2: a promising layered semiconductor.
AB  - Due to the recent expanding interest in two-dimensional layered materials,
      molybdenum disulfide (MoS2) has been receiving much research attention. Having an
      ultrathin layered structure and an appreciable direct band gap of 1.9 eV in the
      monolayer regime, few-layer MoS2 has good potential applications in
      nanoelectronics, optoelectronics, and flexible devices. In addition, the
      capability of controlling spin and valley degrees of freedom makes it a promising
      material for spintronic and valleytronic devices. In this review, we attempt to
      provide an overview of the research relevant to the structural and physical
      properties, fabrication methods, and electronic devices of few-layer MoS2. Recent
      developments and advances in studying the material are highlighted. 

PMID- 24660758
TI  - Heads you win, tails you lose: measuring head circumference.

PMID- 24660757
TI  - Compensation in intergroup relations: an investigation of its structural and
      strategic foundations.
AB  - Recent work in intergroup relations stresses the role of two fundamental
      dimensions, competence and warmth, which organize the perception of social
      groups. A pattern often encountered in people's ratings is one of compensation in
      that a group that is evaluated higher than another group on one of the two
      fundamental dimensions is also judged lower on the other fundamental dimension.
      Based on Social Identity Theory, the present work extends previous research on
      compensation by examining boundary conditions as well as underlying psychological
      processes. Two studies involving experimental and correlational evidence, minimal
      and real groups, and different kinds of conflict, reveal that compensation is
      more likely when the groups are in asymmetrical relation and share a cooperative
      view of the intergroup setting. Our data also suggest that, among members of low
      status groups, compensation is associated with social creativity. In contrast,
      and in line with the 'noblesse oblige' effect, members of the high status group
      would seem to rely on compensation as a means to appear non-discriminatory. 

PMID- 24660759
TI  - Efficacy of enamel matrix derivative with freeze-dried bone allograft or
      demineralized freeze-dried bone allograft in intrabony defects: a randomized
      trial.
AB  - BACKGROUND: Promising clinical outcomes have been reported with the combination
      of enamel matrix derivative (EMD) and allograft materials. Direct comparison
      between EMD with a freeze-dried bone allograft (FDBA) and a demineralized FDBA
      (DFDBA) was evaluated in one case series study. To date, no randomized controlled
      trial has been reported. Therefore, a well-controlled randomized clinical trial
      was conducted to determine the relative efficacy of EMD/FDBA versus EMD/DFDBA
      when managing intrabony defects. METHODS: A randomized parallel trial was
      conducted in a private practice from April 2004 to October 2011. Sixty-nine
      patients were randomly assigned to one of three groups: EMD/FDBA (EF)
      intervention group (n = 23), EMD/DFDBA (ED) intervention group (n = 23), and EMD
      alone without graft material (E) as a negative control group (n = 23). All of the
      grafting material had minocycline added. Each patient had an intrabony defect.
      The primary outcomes were the absolute change in probing depth (PD) reduction and
      clinical attachment level (CAL) gain from baseline to 1- and 3-year follow-up.
      Intrabony defects were surgically treated with EMD/FDBA, EMD/DFDBA, or EMD alone.
      RESULTS: Sixty-seven patients (EF, n = 21: ED, n = 23; E, n = 23) were analyzed.
      All groups demonstrated significant improvement in PD reduction and CAL gain from
      baseline. The changes for PD were as follows (mm, 95% confidence interval [CI]):
      at 1 year: EF (4.4 mm, 4.0 to 4.7), ED (3.7 mm, 3.4 to 4.0), and E (control) (3.3
      mm, 3.0 to 3.6); at 3 years: EF (4.4 mm, 4.1 to 4.8), ED (3.7 mm, 3.4 to 4.0),
      and E (3.1 mm, 2.8 to 3.4). The changes for CAL were as follows (mm, 95% CI): at
      1 year: EF (4.1 mm, 3.8 to 4.5), ED (3.5 mm, 3.0 to 4.0), and E (3.0 mm, 2.5 to
      3.6); at 3 years: EF (4.2 mm, 3.7 to 4.7), ED (3.6 mm, 3.1 to 4.1), and E (3.0
      mm, 2.5 to 3.5). The intervention groups (EF and ED) showed better treatment
      outcomes than the control group at 1 and 3 years. Statistically, the two bone
      graft groups were not significantly different from each other at 1 and 3 years.
      CONCLUSIONS: Both EMD/FDBA and EMD/DFDBA interventions resulted in greater soft
      tissue improvement at 1 and 3 years of follow-up compared to EMD alone. Both
      graft materials worked well in managing deep intrabony defects when combined with
      EMD.

PMID- 24660760
TI  - Evaluating the potential for a Helicobacter pylori drinking water guideline.
AB  - Helicobacter pylori is a microaerophilic, gram-negative bacterium that is linked
      to adverse health effects including ulcers and gastrointestinal cancers. The goal
      of this analysis is to develop the necessary inputs for a quantitative microbial
      risk assessment (QMRA) needed to develop a potential guideline for drinking water
      at the point of ingestion (e.g., a maximum contaminant level, or MCL) that would
      be protective of human health to an acceptable level of risk while considering
      sources of uncertainty. Using infection and gastric cancer as two discrete
      endpoints, and calculating dose-response relationships from experimental data on
      humans and monkeys, we perform both a forward and reverse risk assessment to
      determine the risk from current reported surface water concentrations of H.
      pylori and an acceptable concentration of H. pylori at the point of ingestion.
      This approach represents a synthesis of available information on human exposure
      to H. pylori via drinking water. A lifetime risk of cancer model suggests that a
      MCL be set at <1 organism/L given a 5-log removal treatment because we cannot
      exclude the possibility that current levels of H. pylori in environmental source
      waters pose a potential public health risk. Research gaps include pathogen
      occurrence in source and finished water, treatment removal rates, and
      determination of H. pylori risks from other water sources such as groundwater and
      recreational water. 

PMID- 24660761
TI  - Immature platelet fraction measured on the Sysmex XN hemocytometer predicts
      thrombopoietic recovery after autologous stem cell transplantation.
AB  - OBJECTIVES: A period of thrombocytopenia is common after stem cell
      transplantation (SCT). To prevent serious bleeding complications, prophylactic
      platelet transfusions are administered. Previous studies have shown that a rise
      in immature platelets precedes recovery of platelet count. Our aim was to define
      a cutoff value for immature platelets predicting thrombopoietic recovery within 2
      d. METHODS: Hematological parameters were measured on the Sysmex XN
      hemocytometer. We calculated reference change values (RCV) for platelets in eight
      healthy individuals as marker for platelet recovery. To define a cutoff value, we
      performed ROC analysis using data from 16 autologous SCT patients. RESULTS: RCV
      for platelet concentration was 14.1%. Platelet recovery was observed 13 (median;
      range 9-31) days after SCT. Increase in immature platelet fraction (IPF) before
      platelet recovery was seen in all autologous SCT patients. Optimal cutoff IPF was
      found to be 5.3% for platelet recovery within 2 d (specificity 0.98, sensitivity
      0.47, positive predictive value 0.93). CONCLUSIONS: We identified an optimal
      cutoff value for IPF 5.3% to predict platelet recovery after autologous SCT
      within 2 d. Implementing this cutoff value in transfusion strategy may reduce the
      number of prophylactic platelet transfusions.

PMID- 24660762
TI  - Evaluation of human immunodeficiency virus infection-related left ventricular
      systolic dysfunction by tissue Doppler strain echocardiography.
AB  - OBJECTIVE: Cardiovascular involvement causes significant morbidity and mortality
      among patients with human immunodeficiency virus (HIV) infection. Since the
      introduction of highly active antiretroviral treatment (HAART), subtle changes in
      left ventricular (LV) function, which may be clinically silent, have become more
      pronounced in HIV patients. Echocardiographic strain imaging (SI) may detect
      subclinical myocardial dysfunction at an earlier stage compared with conventional
      echocardiography. The aim of this study was to evaluate tissue Doppler-derived LV
      strain and strain rate (SR) along with conventional measures of LV function in
      asymptomatic, stable adult HIV patients on HAART. METHODS: Twenty-one patients
      with HIV infection (mean age: 37.8 +/- 11.9 years, 11 males) who had no
      cardiovascular complaints and 27 healthy volunteers (mean age: 40.9 +/- 5.8
      years, 14 males) were enrolled. Traditional parameters including LV ejection
      fraction (EF) were measured along with tissue velocity imaging (TVI) and tissue
      Doppler SI parameters using transthoracic echocardiography. RESULTS: The mean
      duration of HIV infection was 30.8 +/- 25.1 (3-120) months. The mean LVEF in HIV
      group was within normal limits but lower than controls (64.5% +/- 10.2% vs. 72.2%
      +/- 6.4%, P = 0.003). There were no differences in other major traditional
      measures, as well as TVI parameters between groups. LV systolic strain and SR
      parameters were impaired indicating subtle LV systolic dysfunction in HIV group.
      No difference in diastolic function was observed between groups. CONCLUSION: Left
      ventricular systolic strain parameters may be utilized to demonstrate subtle LV
      systolic dysfunction in asymptomatic HIV patients.

PMID- 24660763
TI  - An 8-week course of 45 mg of carbonyl iron daily reduces iron deficiency in
      female whole blood donors aged 18 to 45 years: results of a prospective
      randomized controlled trial.
AB  - BACKGROUND: Blood donation is known to contribute to iron deficiency in regular
      blood donors. This study investigated the safety and efficacy of postdonation
      iron replacement to mitigate iron deficiency in blood donors. STUDY DESIGN AND
      METHODS: A total of 282 female whole blood donors aged 18 to 45 were
      prospectively randomized in a double-blinded placebo controlled trial to receive
      an 8-week postdonation course of carbonyl iron (45 mg daily) or placebo. The
      primary endpoint was prevalence of iron deficiency (ferritin < 15 ng/mL) at 12
      weeks postdonation. Secondary endpoints were eligibility to donate based on
      capillary hemoglobin (Hb) and incidence of gastrointestinal (GI) complaints.
      RESULTS: Ferritin levels at Week 12 were significantly higher in donors receiving
      carbonyl iron (17.0 +/- 10.9 ng/mL) compared with those receiving placebo (10.6
      +/- 8.4 ng/mL; p < 0.001). The proportion of iron-deficient donors was
      significantly lower in the carbonyl iron group (51.9%) compared to the placebo
      (80.5%; p < 0.001). The mean Hb level in the carbonyl iron group (134.6 +/- 8.7
      g/L) was significantly higher than in the placebo arm (130.0 +/- 9.9 g/L; p <
      0.001), significantly improving eligibility to donate at Week 12. Significantly
      more donors receiving carbonyl iron had at least one GI side effect (p < 0.001).
      Importantly, 86.7% of donors receiving carbonyl iron indicated that they would
      take iron on an ongoing basis. CONCLUSION: An 8-week postdonation course of 45 mg
      of carbonyl iron significantly reduced iron deficiency and was well tolerated in
      female whole blood donors. Postdonation iron replacement may have a role in a
      broader strategy to optimize donor iron status.

PMID- 24660764
TI  - Development of common metrics for donation attitude, subjective norm, perceived
      behavioral control, and intention for the blood donation context.
AB  - BACKGROUND: The Theory of Planned Behavior has been widely used in blood donation
      research, but the lack of uniform, psychometrically sound measures makes it
      difficult to draw firm conclusions or compare results across studies.
      Accordingly, the goal of this study was to develop such measures of donation
      attitude, subjective norm, perceived behavioral control, and intention. STUDY
      DESIGN AND METHODS: Exploratory and confirmatory factor analyses (CFAs) were
      conducted on survey responses collected from college students (n = 1080). The
      resulting scales were then administered to an independent sample of experienced
      donors (n = 433) for additional CFAs and to test whether the Theory of Planned
      Behavior model provided a good fit to the data. RESULTS: CFAs conducted on both
      samples support the use of six-item scales, with two factors each, to measure
      donation attitude, subjective norm, and perceived behavioral control and a single
      factor three-item scale to measure donation intention. Further, structural
      equation modeling of these measures revealed that the Theory of Planned Behavior
      provided a strong fit to the data (comparative fit index, 0.976; root mean square
      error of approximation, 0.041; standardized root mean square residual, 0.055) and
      accounted for 73.7% of the variance in donation intention. CONCLUSION: The
      present findings confirm the applicability of the Theory of Planned Behavior to
      the blood donation context and more importantly provide psychometric support for
      the future use of four brief measures of donation attitude, subjective norm,
      perceived behavioral control, and intention.

PMID- 24660765
TI  - Similar donors-similar blood?
AB  - BACKGROUND: Red blood cell (RBC) storage lesions have been suggested as
      contributing factors to suboptimal clinical outcomes. While undesirable effects
      of storage are well documented, their clinical relevance is still debated. Focus
      on storage time as the sole determinant of RBC quality ignores the variability in
      cell properties that may depend on factors other than age. Mechanical fragility
      (MF) aggregately reflects many storage-related functional and structural changes.
      This study evaluates interdonor versus intradonor variability, throughout
      storage, of both MF and autohemolysis (AH). STUDY DESIGN AND METHODS: Thirteen
      uniformly manufactured RBC units were collected initially as whole blood from
      nonsmoking, group A+, male Caucasian research donors. Mechanical stress was
      applied using a bead mill with oscillation at 50 Hz over durations varying from
      0.5 to 60 minutes. MF profiles were described in terms of percent hemolysis after
      stresses of specified durations. Two months later, 11 of the 13 donors returned
      and assays were performed using the same protocol to allow comparison of
      intradonor versus interdonor variation. RESULTS: At 5 days postcollection, RBC MF
      profiles exhibited marked interdonor variability (up to twofold) overall. Both
      autolysis and MF across all units increased during storage-with rates of these
      increases varying by up to 10-fold for certain MF variables. Especially high AH
      and MF were observed for an outlier donor (with p < 0.05), for whom follow-up
      revealed previously undisclosed hereditary hypertriglyceridemia (levels exceeding
      approx. 1000 mg/dL). CONCLUSIONS: RBCs, even from similar donors, vary
      significantly in levels and changes of both AH and MF, the clinical significance
      of which must still be ascertained. While further study is needed, donors with
      severe hypertriglyceridemia may not be appropriate as blood donors due to the
      unacceptable level of hemolysis observed during storage of our affected study
      subject.

PMID- 24660766
TI  - Injury pattern as an indication of seat belt failure in ejected vehicle
      occupants.
AB  - Prior authors have suggested that when occupant ejection occurs in association
      with a seat belt failure, entanglement of the outboard upper extremity (OUE) with
      the retracting shoulder belt will invariably occur, leaving injury pattern
      evidence of belt use. In the present investigation, the authors assessed this
      theory using data accessed from the NASS-CDS for ejected front seat occupants of
      passenger vehicles. Logistic regression models were used to assess the
      associations between seat belt failure status and injuries. Injury types
      associated with seat belt failure were significant OUE and head injuries (OR =
      3.87, [95% CI 1.2, 13.0] and 3.1, [95% CI 1.0, 9.7], respectively). The two
      injury types were found to be a predictor of seat belt use and subsequent failure
      only if combined with a high (>=0.8) precrash probability of belt use. The injury
      pattern associated with a seat belt failure-related ejection has limited use in
      the forensic investigation of crash-related ejections. 

PMID- 24660768
TI  - Interventions to improve cervical cancer screening uptake amongst young women: a
      systematic review.
AB  - OBJECTIVES: In view of declining screening uptake in young women, this review
      aims to summarise the available evidence relating to interventions designed to
      increase cervical screening uptake amongst women aged <= 35 years. METHODS:
      Electronic databases were searched and further articles located by manual
      searches. Study designs employing a valid comparison group and including women
      aged <= 35 years published through 2012 were considered. Data was extracted on
      the uptake from either screening programme statistics or as reported by the study
      subjects. A narrative synthesis was undertaken for each category of interventions
      identified. RESULTS: Ninety-two records were screened with 36 articles retrieved
      for further assessment. Four studies met the inclusion criteria, two of which
      evaluated more than one intervention. One of the studies evaluated the use of a
      modified invitation letter and reported no significant increase in uptake
      compared to a standard invitation. Three studies investigated the use of a
      reminder letter, with two reporting a positive effect on screening uptake in
      women aged 24-34. Three studies were included which supported the use of
      physician and telephone reminders. One study on HPV self-sampling reported a
      positive effect when compared with a reminder letter. CONCLUSIONS: There is a
      lack of randomised controlled trials designed to specifically address falling
      cervical screening uptake in amongst young women. Cervical screening programmes
      need to look beyond the use of invitation/reminders letters in this group of
      women to develop interventions which attempt to overcome as many barriers to
      uptake as possible.

PMID- 24660767
TI  - Late HIV diagnosis: Differences by rural/urban residence, Florida, 2007-2011.
AB  - The purpose of this retrospective cohort study was to identify individual-level
      demographic and community-level socioeconomic and health care resource factors
      associated with late diagnosis of HIV in rural and urban areas of Florida.
      Multilevel modeling was conducted with linked 2007-2011 Florida HIV surveillance,
      American Community Survey, Area Health Resource File, and state counseling and
      testing data. Late diagnosis (defined as AIDS diagnosis within 3 months of HIV
      diagnosis) was more common in rural than urban areas (35.8% vs. 27.4%)
      (p<0.0001). This difference persisted after controlling for age, sex,
      race/ethnicity, HIV transmission mode, country of birth, and diagnosis year
      (adjusted OR 1.39; 95% CI 1.17-1.66). In rural areas, older age and male sex were
      associated with late HIV diagnosis; zip code-level socioeconomic and county level
      health care resource variables were not associated with late diagnosis in rural
      areas. In urban areas only, Hispanic and non-Hispanic black race/ethnicity,
      foreign birth, and heterosexual mode of transmission were additionally associated
      with late HIV diagnosis. These findings suggest that, in rural areas, enhanced
      efforts are needed to target older individuals and men in screening programs and
      that studies of psychosocial and structural barriers to HIV testing in rural and
      urban areas be pursued.

PMID- 24660769
TI  - Expanding the spectrum of pulmonary histopathological manifestations of anti
      synthetase syndrome: anti-EJ-associated acute fibrinous and organizing pneumonia.

PMID- 24660770
TI  - Why can organic liquids move easily on smooth alkyl-terminated surfaces?
AB  - The dynamic dewettability of a smooth alkyl-terminated sol-gel hybrid film
      surface against 17 probe liquids (polar and nonpolar, with high and low surface
      tensions) was systematically investigated using contact angle (CA) hysteresis and
      substrate tilt angle (TA) measurements, in terms of their physicochemical
      properties such as surface tension, molecular weight/volume, dielectric constant,
      density, and viscosity. We found that the dynamic dewettability of the hybrid
      film markedly depended not on the surface tensions but on the dielectric
      constants of the probe liquids, displaying lower resistance to liquid drop
      movement with decreasing dielectric constant (epsilon < 30). Interfacial analysis
      using the sum-frequency generation (SFG) technique confirmed that the
      conformation of surface-tethered alkyl chains was markedly altered before and
      after contact with the different types of probe liquids. When probe liquids with
      low dielectric constants were in contact with our surface, CH3 groups were
      preferentially exposed at the solid/liquid interface, leading to a reduction in
      surface energy. Because of such local changes in surface energy at the three
      phase contact line of the probe liquid, the contact line can move continuously
      from low-surface-energy (solid/liquid) areas to surrounding high-surface-energy
      (solid/air) areas without pinning. Consequently, the organic probe liquids with
      low dielectric constants can move easily and roll off when tilted only slightly,
      independent of the magnitude of CAs, without relying on conventional surface
      roughening and perfluorination. 

PMID- 24660773
TI  - Substance P at the neuro-immune crosstalk in the modulation of inflammation,
      asthma and antimicrobial host defense.
AB  - Substance P, a neuropeptide belonging to the tachykinin family is a pleiotropic
      peptide with specific neural activities and involved in immunomodulation and
      antimicrobial host defense. It has been found to modulate a variety of
      inflammatory processes, including acute pancreatitis, sepsis, systemic
      inflammatory response syndrome and asthma. Also notably, substance P shares
      common bio-physical and -chemical properties such as low molecular mass,
      cathionicity and amphipathicity with antimicrobial peptides. It is therefore
      suggested to take part in host defense at specialized locations. The review aims
      to highlight undated understanding on substance P in inflammation, allergy and
      its antimicrobial activities with potential implications in infection and host
      defense. Therapeutic implications of the peptide, modulators of peptide
      expression and receptor signalling will be highlighted in each topic. Taken
      together, these topics will be of significant values for future pharmaceutical
      investigation and application of the field. 

PMID- 24660772
TI  - Apoptosis of NOD.H2 h4 thyrocytes by low concentrations of iodide is associated
      with impaired control of oxidative stress.
AB  - BACKGROUND: Enhanced iodide intake in NOD.H2(h4) mice accelerates the incidence
      and severity of spontaneous autoimmune thyroiditis (SAT) via an unknown
      mechanism. A plausible hypothesis is that iodide-induced apoptosis of thyrocytes
      can create imbalances in antigenic load and/or disruption of immunoregulatory
      mechanisms that facilitate activation of autoreactive T cells in cervical lymph
      nodes draining the thyroid. METHODS: We examined whether NOD.H2(h4) thyrocytes,
      exposed to low NaI concentrations in vitro, are more susceptible to apoptosis
      compared to thyrocytes from CBA/J mice, which are resistant to iodide-accelerated
      SAT (ISAT). We also looked, at the transcriptional level, for differential
      activation of genes involved in apoptosis or oxidative stress pathways that may
      account for potential differences in iodide-mediated apoptosis between NOD.H2(h4)
      and CBA/J thyrocytes. RESULTS: We report that NOD.H2(h4) thyrocytes, cultured for
      24 h at very low (4-8 MUM) concentrations of NaI, exhibit high levels (40-55%) of
      apoptosis, as assessed microscopically following staining with fluorescent
      caspase inhibitors. Similar treatment of thyrocytes from CBA/J mice, which are
      resistant to ISAT, yielded significantly lower (10-20%) apoptotic rates.
      Expression analysis by real-time polymerase chain reaction using arrays of
      apoptosis- and oxidative stress-related genes showed that NaI intake upregulates
      the expression of 22 genes involved in ROS metabolism and/or antioxidant function
      in CBA/J thyrocytes, whereas only two of these genes were upregulated in
      NOD.H2(h4) thyrocytes. Among the set of overexpressed genes were those encoding
      thyroid peroxidase (Tpo; 5.77-fold), glutathione peroxidases (Gpx2, Gpx4, Gpx7;
      2.03-3.14-fold), peroxiredoxins (Prdx1, Prdx2, Prdx5; 2.27-2.97-fold), superoxide
      dismutase 1 (Sod1; 3.57-fold), thioredoxin 1 (Txn1; 2.13-fold), and the
      uncoupling proteins 2 and 3 (Ucp2, Ucp3; 2.01-2.15-fold). CONCLUSIONS: The
      results demonstrate that an impaired control of oxidative stress mechanisms is
      associated with the observed high susceptibility of NOD.H2(h4) thyrocytes to NaI
      mediated apoptosis, and suggest a contributing factor for the development of ISAT
      in this strain.

PMID- 24660771
TI  - Oxytocin and vasopressin receptor polymorphisms interact with circulating
      neuropeptides to predict human emotional reactions to stress.
AB  - Oxytocin (OT) and a polymorphism (rs53576) in the oxytocin receptor gene (OXTR)
      have been independently associated with stress reactivity, whereas oxytocin's
      sister peptide, arginine vasopressin (AVP) and polymorphisms in the vasopressin
      receptor gene (AVPR1A) have been independently associated with aggressive
      behavior. In this study, 68 men and 98 women were genotyped for the OXTR rs53576
      polymorphism and the AVPR1A RS1 polymorphism. Baseline and poststressor levels of
      plasma OT, plasma AVP, positive affect, and anger were assessed. Women, but not
      men, with high levels of poststressor OT and the GG genotype of rs53576 felt the
      most positive affect after the stressor. Men, but not women, with high levels of
      poststressor AVP and the 320 allele of the RS1 polymorphism reported more
      poststressor anger than noncarriers. These data constitute the first evidence
      that oxytocin and vasopressin receptor genes interact with levels of OT and AVP
      to predict sex-specific emotional stress responses.

PMID- 24660774
TI  - How to optimize patient selection for robot-assisted radical prostatectomy:
      functional outcome analyses from a tertiary referral center.
AB  - INTRODUCTION: The role of surgical approach on functional outcomes recovery in
      prostate cancer (PCa) patients treated with bilateral nerve-sparing radical
      prostatectomy (BNSRP) is still debated. In this study, we examine the association
      between the surgical approach and functional outcomes after BNSRP. PATIENTS AND
      METHODS: The study included 609 patients treated with robot-assisted radical
      prostatectomy (RARP) or open radical prostatectomy (ORP) between June 2008 and
      January 2011. Erectile function recovery was defined as an International Index of
      Erectile Function-Erectile Function domain (IIEF-EF) score >=22. Urinary
      continence recovery was defined as being completely pad-free over a 24-hour
      period. Patients were stratified according to their probability of postoperative
      erectile dysfunction and urinary incontinence, according to previously published
      predictive models. Multivariable logistic regression tested the association
      between the surgical approach and functional outcomes recovery in the overall
      population after stratifying patients according to their risk of erectile
      dysfunction and urinary incontinence. RESULTS: Patients treated with RARP had
      higher 2-year erectile function (52.1% vs 67.8%; P<0.001) and urinary continence
      (72.0% vs 87.4%; P<0.001) recovery rates as compared to their ORP counterparts.
      After stratification according to the erectile dysfunction risk, RARP led to
      higher erectile function recovery rates in the low- and intermediate-risk
      erectile dysfunction groups (all P<0.001).This did not hold true, however, in
      patients at high risk of erectile dysfunction (P=0.5). Similarly, when patients
      were stratified according to their urinary incontinence risk, RARP was associated
      with a higher probability of urinary continence recovery in the very low, low,
      and intermediate risk groups only (all P<0.001). This did not hold true, however,
      in the group of men at high risk of postoperative urinary incontinence (P=0.8).
      CONCLUSIONS: RARP leads to higher urinary continence and erectile function
      recovery rates compared with ORP. Not all patients benefit from this approach to
      the same extent, however. Accurate preoperative patient selection would result in
      substantial savings for the health care system.

PMID- 24660775
TI  - Detection of protein-protein interactions by proximity-driven S(N)Ar reactions of
      lysine-linked fluorophores.
AB  - Critical protein-protein interactions are ubiquitous in biology. To provide a new
      method to detect these interactions, we designed and synthesized fluorinated
      bromopyronins as molecular probes. These electrophilic compounds rapidly react
      with amines via a S(N)Ar mechanism to form modestly electrophilic aminopyronin
      fluorophores. To investigate whether proteins modified with aminopyronins might
      selectively transfer these fluorophores between proximal lysine residues at
      protein-protein interfaces, immunoglobulin-G (IgG) was conjugated to fluorinated
      pyronins and added to unlabeled Protein A (SpA) from S. aureus. Analysis by gel
      electrophoresis and mass spectrometry revealed transfer of this fluorophore from
      IgG to specific lysines of its binding partner SpA but not to bovine serum
      albumin (BSA) as a nonbinding control. Examination of an X-ray structure of IgG
      bound to SpA revealed that the fluorophore was selectively transferred between
      amino groups of lysines that reside within ~10 A at the protein-protein
      interface. To evaluate whether this approach could be used to identify
      interactions with endogenous cellular proteins, pyronin-modified Rnase A was
      added to crude extracts of human HeLa cells. Analysis of interacting proteins by
      gel electrophoresis revealed the endogenous ribonuclease inhibitor as the primary
      cellular target. Given that proximal lysine residues frequently reside at protein
      protein interfaces, this method may facilitate identification of diverse protein
      protein interactions present in complex biological matrices.

PMID- 24660776
TI  - Two orders of magnitude fluorescence enhancement of aluminum phthalocyanines by
      gold nanocubes: a remarkable improvement for cancer cell imaging and detection.
AB  - The metal-enhanced fluorescence (MEF) by metal nanoparticles is a useful
      technique for fluorescence detections in biological systems. The MEF effects with
      gold nanorods (AuNRs) and nanocubes (AuNCs) for fluorescence enhancements of
      sulfonated aluminum phthalocyanine (AlPcS), a commonly used and clinical approved
      photosensitizer for photodynamic therapy of cancers, were studied in this work.
      For the AuNRs which have the low aspect ratios with the corresponding
      longitudinal surface plasma resonance (LSPR) band in the region of 600-750 nm,
      the fluorescence quenching of conjugated AlPcS was found. Whereas for the AuNRs
      that have the LSPR bands of 800-900 nm, the MEF of AlPcS was obtained with the
      enhancing factor of 2-6 times, respectively. Using AuNCs, a great enhancement of
      AlPcS fluorescence was achieved with an enhancing factor of 150 times. Using two
      cancer cell lines as in vitro models, an outstanding fluorescence enhancement of
      AlPcS-AuNCs conjugates in cells, relative to AlPcS alone, was obtained under one
      photon excitation (OPE) of 405 nm. Moreover, the bright fluorescence image of
      AlPcS-AuNCs in cells was also achieved under the two-photon excitation (TPE) of
      an 800 nm femtosecond laser. The high-quality cell imaging with either OPE or TPE
      demonstrated the potential of AlPcS-AuNCs in cancer cell detections. 

PMID- 24660778
TI  - The role of transcription factors in prostate cancer and potential for future RNA
      interference therapy.
AB  - INTRODUCTION: Prostate cancer is a leading cause of cancer-related death in men
      and current treatments offer only a modest survival benefit in advanced stages of
      the disease. RNA interference (RNAi) is a therapeutic option that has received
      great attention in recent years with the potential to treat a variety of
      disorders, including prostate cancer. Transcription factors are cellular proteins
      that can up-regulate or down-regulate the transcription of genes and offer
      promising therapeutic targets. AREAS COVERED: This review will focus on
      transcription factors that have been identified as key molecules in drug
      resistance, disease progression and metastases in prostate cancer, which may
      offer potential as therapeutic targets for RNAi in the future. EXPERT OPINION: By
      identifying therapeutically viable transcription factor targets in prostate
      cancer, it is hoped that treatment strategies using RNAi will augment the effect
      of current chemotherapy regimens, slow disease progression and reduce metastases
      in prostate cancer, resulting in disease regression.

PMID- 24660780
TI  - Crater lake habitat predicts morphological diversity in adaptive radiations of
      cichlid fishes.
AB  - Adaptive radiations provide an excellent opportunity for studying the correlates
      and causes for the origin of biodiversity. In these radiations, species diversity
      may be influenced by either the ecological and physical environment, intrinsic
      lineage effects, or both. Disentangling the relative contributions of these
      factors in generating biodiversity remains a major challenge in understanding why
      a lineage does or does not radiate. Here, we examined morphological variation in
      body shape for replicate flocks of Nicaraguan Midas cichlid fishes and tested its
      association with biological and physical characteristics of their crater lakes.
      We found that variability of body elongation, an adaptive trait in freshwater
      fishes, is mainly predicted by average lake depth (N = 6, P < 0.001, R(2) =
      0.96). Other factors considered, including lake age, surface area, littoral zone
      area, number of co-occurring fish species, and genetic diversity of the Midas
      flock, did not significantly predict morphological variability. We also showed
      that lakes with a larger littoral zone have on average higher bodied Midas
      cichlids, indicating that Midas cichlid flocks are locally adapted to their
      crater lake habitats. In conclusion, we found that a lake's habitat predicts the
      magnitude and the diversity of body elongation in repeated cichlid adaptive
      radiations.

PMID- 24660779
TI  - Elucidating a key component of cancer metastasis: CXCL12 (SDF-1alpha) binding to
      CXCR4.
AB  - The chemotactic signaling induced by the binding of chemokine CXCL12 (SDF-1alpha)
      to chemokine receptor CXCR4 is of significant biological importance and is a
      potential therapeutic axis against HIV-1. However, as CXCR4 is overexpressed in
      certain cancer cells, the CXCL12:CXCR4 signaling is involved in tumor metastasis,
      progression, angiogenesis, and survival. Motivated by the pivotal role of the
      CXCL12:CXCR4 axis in cancer, we employed a comprehensive set of computational
      tools, predominantly based on free energy calculations and molecular dynamics
      simulations, to obtain insights into the molecular recognition of CXCR4 by
      CXCL12. We report, what is to our knowledge, the first computationally derived
      CXCL12:CXCR4 complex structure which is in remarkable agreement with experimental
      findings and sheds light into the functional role of CXCL12 and CXCR4 residues
      which are associated with binding and signaling. Our results reveal that the
      CXCL12 N-terminal domain is firmly bound within the CXCR4 transmembrane domain,
      and the central 24-50 residue domain of CXCL12 interacts with the upper N
      terminal domain of CXCR4. The stability of the CXCL12:CXCR4 complex structure is
      attributed to an abundance of nonpolar and polar intermolecular interactions,
      including salt bridges formed between positively charged CXCL12 residues and
      negatively charged CXCR4 residues. The success of the computational protocol can
      mainly be attributed to the nearly exhaustive docking conformational search, as
      well as the heterogeneous dielectric implicit water-membrane-water model used to
      simulate and select the optimum conformations. We also recently utilized this
      protocol to elucidate the binding of an HIV-1 gp120 V3 loop in complex with
      CXCR4, and a comparison between the molecular recognition of CXCR4 by CXCL12 and
      the HIV-1 gp120 V3 loop shows that both CXCL12 and the HIV-1 gp120 V3 loop share
      the same CXCR4 binding pocket, as they mostly interact with the same CXCR4
      residues. 

PMID- 24660781
TI  - Soluble polymer-based, blown bubble assembly of single- and double-layer
      nanowires with shape control.
AB  - We present here an efficient blown bubble method for large-scale assembly of
      semiconducting nanowires, with simultaneous control on the material shape. As
      synthesized Te nanowires in powder form are dispersed in a polymethylmethacrylate
      (PMMA) solution, assembled in a large size bubble blown from the solution, and
      then transferred (repeatedly) to arbitrary substrates. By this way, we have
      obtained single-layer (aligned) and double-layer (crossed) Te nanowires as well
      as buckled Te nanosprings which are converted from initially straight nanowires
      in situ during bubble blowing. The PMMA bubble film can be removed by direct
      dissolution in acetone to expose nanostructures with clean surface while
      maintaining original configuration. After matrix removal, these clean nanowire
      and nanospring arrays can be fabricated into functional nanoelectronic devices
      such as photodetectors and gas sensors with high performance. 

PMID- 24660782
TI  - The unusual mechanism of partial Fermi level pinning at metal-MoS2 interfaces.
AB  - Density functional theory calculations are performed to unravel the nature of the
      contact between metal electrodes and monolayer MoS2. Schottky barriers are shown
      to be present for a variety of metals with the work functions spanning over 4.2
      6.1 eV. Except for the p-type Schottky contact with platinum, the Fermi levels in
      all of the studied metal-MoS2 complexes are situated above the midgap of MoS2.
      The mechanism of the Fermi level pinning at metal-MoS2 contact is shown to be
      unique for metal-2D-semiconductor interfaces, remarkably different from the well
      known Bardeen pinning effect, metal-induced gap states, and defect/disorder
      induced gap states, which are applicable to traditional metal-semiconductor
      junctions. At metal-MoS2 interfaces, the Fermi level is partially pinned as a
      result of two interface behaviors: first by a metal work function modification by
      interface dipole formation due to the charge redistribution, and second by the
      production of gap states mainly of Mo d-orbitals character by the weakened
      intralayer S-Mo bonding due to the interface metal-S interaction. This finding
      would provide guidance to develop approaches to form Ohmic contact to MoS2. 

PMID- 24660784
TI  - Analysis of the effects of communication and surveillance facility service
      outages on traffic separations.
AB  - This study examines air traffic separations in the service volumes of
      communication and surveillance facilities that experienced service outages. The
      data sample consists of 338 unscheduled service outages that happened in 2010 and
      2011 at facilities located in the vicinity of 15 major traffic hubs. For each
      outage, radar track data were collected and used to calculate traffic separations
      during the period of 30 minutes before to 30 minutes after an outage. Then, the
      separation index, which indicates the percentage of horizontal separation
      retained between two aircraft at the same altitude, was estimated. The separation
      index and loss of separation events were analyzed using lognormal and negative
      binomial regression models. The results suggest that the count of separation
      events peaks during the 15 minutes after an outage. In addition, traffic
      collision avoidance system resolution advisory (TCAS RA) encounters and Category
      A separation events are 1.31 times more likely during the 30 minutes following
      the beginning of a service outage, as compared to the 30 minutes before the
      outage, for both types of facilities. Also, the separation index values are 19%
      lower following a surveillance facility outage and 4% lower following a
      communication facility service loss. This study provides evidence that
      unscheduled service outages of air traffic management facilities are associated
      with lost or reduced traffic separations and thus can be considered precursors to
      hazardous loss of separation events. 

PMID- 24660783
TI  - In vitro and in vivo characterization of three different modes of pump operation
      when using a left ventricular assist device as a right ventricular assist device.
AB  - Dual rotary left ventricular assist devices (LVADs) have been used clinically to
      support patients with biventricular failure. However, due to the lower vascular
      resistance in the pulmonary circulation compared with its systemic counterpart,
      excessively high pulmonary flow rates are expected if the right ventricular
      assist device (RVAD) is operated at its design LVAD speed. Three possible
      approaches are available to match the LVAD to the pulmonary circulation:
      operating the RVAD at a lower speed than the LVAD (mode 1), operating both pumps
      at their design speeds (mode 2) while relying on the cardiovascular system to
      adapt, and operating both pumps at their design speeds while restricting the
      diameter of the RVAD outflow graft (mode 3). In this study, each mode was
      characterized using in vitro and in vivo models of biventricular heart failure
      supported with two VentrAssist LVADs. The effect of each mode on arterial and
      atrial pressures and flow rates for low, medium, and high vascular resistances
      and three different contractility levels were evaluated. The amount of
      speed/diameter adjustment required to accommodate elevated pulmonary vascular
      resistance (PVR) during support with mode 3 was then investigated. Mode 1
      required relatively low systemic vascular resistance to achieve arterial
      pressures less than 100 mm Hg in vitro, resulting in flow rates greater than 6
      L/min. Mode 2 resulted in left atrial pressures above 25 mm Hg, unless left heart
      contractility was near-normal. In vitro, mode 3 resulted in expected arterial
      pressures and flow rates with an RVAD outflow diameter of 6.5 mm. In contrast,
      all modes were achievable in vivo, primarily due to higher RVAD outflow graft
      resistance (more than 500 dyn.s/cm(5)), caused by longer cannula. Flow rates
      could be maintained during instances of elevated PVR by increasing the RVAD speed
      or expanding the outflow graft diameter using an externally applied variable
      graft occlusion device. In conclusion, suitable hemodynamics could be produced by
      either restricting or not restricting the right outflow graft diameter; however,
      the latter required an operation of the RVAD at lower than design speed.
      Adjustments in outflow restriction and/or RVAD speed are recommended to
      accommodate varying PVR.

PMID- 24660785
TI  - Degeneration and dysfunction of retinal neurons in acute ocular hypertensive
      rats: involvement of calpains.
AB  - PURPOSE: Retinal ischemic diseases primarily lead to damage of the inner retinal
      neurons. Electrophysiological studies also suggest impairment of the inner
      retinal neurons. Our recent studies with acute ocular hypertensive rats confirmed
      damage predominantly in the inner retinal layer along with the ganglion cell
      layer, changes that are ameliorated by the calpain inhibitor SNJ-1945. However,
      we do not know which specific neuronal cells in the inner retinal layer are
      damaged by calpains. Thus, the purpose of the present study was to identify
      specific calpain-damaged neuronal cells in the inner retina from acute ocular
      hypertensive rats. METHODS: Intraocular pressure was elevated to 110 mm Hg for 40
      min. One hour after ocular hypertension (OH), SNJ-1945 was administrated as a
      single oral dose of 50 mg/kg. Retinal function was assessed by scotopic
      electroretinography (ERG). Histological degeneration was evaluated by hematoxylin
      and eosin, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end
      labeling (TUNEL), and immunostaining in thin sections and flat mounts of the
      retina. Calpain activation was determined by proteolysis of the calpain substrate
      alpha-spectrin. RESULTS: OH caused calpain activation, increased TUNEL-positive
      staining, decreased thickness of the inner nuclear layer (INL), and decreased
      amplitudes of the ERG a- and b-waves and oscillatory potentials (OPs). SNJ-1945
      significantly inhibited calpain activation and the decrease in ERG values.
      Interestingly, the changes in the b-wave and OPs amplitudes were significantly
      correlated to changes in the thickness of the INL. In the inner retinal layer,
      the numbers of rod bipolar, cone-ON bipolar, and amacrine cells were decreased
      after OH. SNJ-1945 suppressed the loss of cone-ON bipolar and amacrine cells, but
      did not inhibit the loss of rod bipolar cells. We also observed increased glial
      fibrillary acid protein-positive staining in the Muller cells after OH and the
      treatment with SNJ-1945. CONCLUSIONS: Calpains may contribute to ischemic retinal
      dysfunction by causing the loss of cone-ON bipolar and amacrine cells and causing
      the activation of Muller cells. Calpain inhibitor SNJ-1945 may be a candidate
      compound for treatment of retinal ischemic disease.

PMID- 24660786
TI  - Efficacy of just-in-time plerixafor rescue for Hodgkin's lymphoma patients with
      poor peripheral blood stem cell mobilization.
AB  - BACKGROUND: Plerixafor is a Food and Drug Administration-approved agent for
      improving peripheral blood stem cell (PBSC) mobilization in filgrastim
      (granulocyte-colony-stimulating factor [G-CSF])-stimulated patients with multiple
      myeloma and non-Hodgkin's lymphoma. Limited information is available on its use
      in Hodgkin's lymphoma (HL) patients. We describe our experience with plerixafor
      as an immediate rescue agent in HL patients with poor PBSC mobilization. STUDY
      DESIGN AND METHODS: We retrospectively reviewed the collection data of 27
      consecutive HL patients at our center in whom plerixafor was added to rescue a
      failing PBSC collection after G-CSF and chemotherapy (26) or G-CSF alone (1).
      Plerixafor was added in 11 patients due to peripheral blood (PB) CD34+ counts
      that persisted below the threshold (>10 * 10(6) /L) to initiate collection
      (median, 1.47 * 10(6) ; range 0 * 10(6) -6.28 * 10(6) /L) and in 16 patients due
      to low collection yields, who had a median yield of 0.33 * 10(6) (0.14 * 10(6) 
      0.65 * 10(6) ) CD34+ cells/kg on the last collection before plerixafor
      administration. RESULTS: After a median of 2 (range, 2-4) collections with
      plerixafor, the patients collected a median of 1.82 * 10(6) (0.52 * 10(6) -11.14
      * 10(6) ) CD34+ cells/kg. The addition of plerixafor enabled 20 patients (74.1%)
      to reach the 2.0 * 10(6) CD34+ cells/kg minimum required for autologous stem cell
      transplantation (ASCT) during the same collection cycle. Subsequent
      remobilization in three patients with plerixafor enabled all three to reach this
      goal. CONCLUSION: Plerixafor can be used in HL patients with poor mobilization as
      a rescue agent and boosts mobilization sufficiently in most patients in the same
      collection attempt, thus not only permitting ASCT, but also avoiding
      remobilization and the associated costs, treatment delays, and patient
      inconvenience.

PMID- 24660787
TI  - Simultaneous homicide-suicide: a case report of double drowning.
AB  - Homicide-suicide is a tragic phenomenon which typically does not result in a
      criminal charge or trial. However, correct diagnosis and classification of
      homicide-suicide cases are important to determine the perpetrators and dynamics
      of each category properly. The deaths in the homicide-suicide acts can be divided
      into two categories with respect to the number of involved individuals: dyadic
      deaths and triple or multiple deaths. These two categories can also be divided
      into two subgroups according to the chronology of the incidents: simultaneous
      deaths and consecutive deaths. Herein, a simultaneous homicide-suicide case of a
      father and daughter where both deaths occurred through drowning which was not
      found in the selected literature review and where the victim was a child is
      presented. The article aims to clarify the term discrepancies about multiple
      death cases in the literature and to discuss the pathological and psychosocial
      characteristics of the simultaneous dyadic death cases. 

PMID- 24660788
TI  - Anal cancer trends in Puerto Rico from 1985 to 2005: the potential impact of the
      AIDS epidemic.

PMID- 24660789
TI  - The Val/Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene
      predicts decline in perceptual speed in older adults.
AB  - The brain-derived neurotrophic factor (BDNF) promotes activity-dependent synaptic
      plasticity, and contributes to learning and memory. We investigated whether a
      common Val66Met missense polymorphism (rs6265) of the BDNF gene is associated
      with individual differences in cognitive decline (marked by perceptual speed) in
      old age. A total of 376 participants of the Berlin Aging Study, with a mean age
      of 83.9 years at first occasion, were assessed longitudinally up to 11 times
      across more than 13 years on the Digit-Letter task. Met carriers (n = 123, 34%)
      showed steeper linear decline than Val homozygotes (n = 239, 66%); the
      corresponding contrast explained 2.20% of the variance in change in the entire
      sample, and 3.41% after excluding individuals at risk for dementia. These effects
      were not moderated by sex or socioeconomic status. Results are consistent with
      the hypothesis that normal aging magnifies the effects of common genetic
      variation on cognitive functioning.

PMID- 24660790
TI  - IDE (rs6583817) polymorphism and pulse pressure are independently and
      interactively associated with level and change in executive function in older
      adults.
AB  - OBJECTIVE: We report a gene * environment (health) study focusing on concurrent
      performance and longitudinal change in a latent-variable executive function (EF)
      phenotype. Specifically, we tested the independent and interactive effects of a
      recently identified insulin degrading enzyme genetic polymorphism (IDE rs6583817)
      and pulse pressure (PP; one prominent aging-related vascular health indicator)
      across up to 9 years of EF data in a sample of older adults from the Victoria
      Longitudinal Study. Both factors vary across a continuum of risk-elevating to
      risk-reducing and have been recently linked to normal and impaired cognitive
      aging. METHOD: We assembled a genotyped and typically aging group of older adults
      (n = 599, M age = 66 years at baseline), following them for up to 3 longitudinal
      waves (M interval = 4.4 years). We used confirmatory factor analyses, latent
      growth modeling, and path analyses to pursue 3 main research goals. RESULTS:
      First, the EF single factor model was confirmed comprising 4 executive function
      tasks and it demonstrated measurement invariance across the waves. Second, older
      adults with the major IDE G allele exhibited better EF outcomes than homozygotes
      for the minor A allele at the centering age of 75 years. Adults with higher PP
      performed more poorly on EF tasks at age 75 years and exhibited greater EF
      longitudinal decline. Third, gene * health interaction analyses showed that
      worsening vascular health (higher PP) differentially affected EF performance in
      older adults with the IDE G allele. CONCLUSION: Genetic interaction analyses can
      reveal differential and magnifying effects on cognitive phenotypes in aging. In
      the present case, pulse pressure is confirmed as a risk factor for concurrent and
      changing cognitive health in aging, but the effects operate differently across
      the risk and protective allelic distribution of this IDE gene.

PMID- 24660791
TI  - The benefits of staying active in old age: physical activity counteracts the
      negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory
      functioning.
AB  - PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and
      they influence episodic memory performance in old age. Physical activity,
      however, has been shown to protect against age-related decline and counteract
      genetic influences on cognition. The aims of this study were to assess whether
      (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms
      influences cognitive performance in old age; and (b) if physical activity
      moderates this effect. Data from the SNAC-K population-based study were used,
      including 2,480 individuals (age range = 60 to 100 years) free of dementia at
      baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory,
      perceptual speed, knowledge, and verbal fluency were administered. Physical
      activity was measured using self-reports. Individuals who had engaged in frequent
      health- or fitness-enhancing activities within the past year were compared with
      those who were inactive. Genetic risk scores were computed based on an
      integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele),
      BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was
      associated with reduced episodic memory performance, controlling for age,
      education, vascular risk factors, chronic diseases, activities of daily living,
      and APOE gene status. Critically, physical activity attenuated the effects of
      genetic risk on episodic memory. Our findings suggest that participants with high
      genetic risk who maintain a physically active lifestyle show selective benefits
      in episodic memory performance.

PMID- 24660792
TI  - Meta-analysis of the age-related positivity effect: age differences in
      preferences for positive over negative information.
AB  - In contrast to long-held axioms of old age as a time of "doom and gloom,"
      mounting evidence indicates an age-related positivity effect in attention and
      memory. However, several studies report inconsistent findings that raise critical
      questions about the effect's reliability, robustness, and potential moderators.
      To address these questions, we conducted a systematic meta-analysis of 100
      empirical studies of the positivity effect (N = 7,129). Results indicate that the
      positivity effect is reliable and moderated by theoretically implicated
      methodological and sample characteristics. The positivity effect is larger in
      studies that do not constrain (vs. constrain) cognitive processing-reflecting
      older adults' natural information processing preferences-and in studies
      incorporating wider (vs. narrower) age comparisons. Analyses indicated that older
      adults show a significant information processing bias toward positive versus
      negative information, whereas younger adults show the opposite pattern. We
      discuss implications of these findings for theoretical perspectives on emotion
      cognition interactions across the adult life span and suggest future research
      directions.

PMID- 24660793
TI  - Multidirectional age differences in anger and sadness.
AB  - Age differences in anger and sadness were explored, focusing on the intensity and
      frequency of these experiences in everyday life and their implicit associations
      with the self. Ninety-six young and older adults participated in the Day
      Reconstruction Method, in which emotional experiences on a typical day were
      recorded, and in 2 implicit association tests assessing implicit self-concepts
      for anger and sadness. Older adults experienced anger less frequently and less
      intensively than young adults, but there were no age differences in sadness. In
      comparison with their younger counterparts, older adults showed a greater IAT
      effect in the implicit anger test, suggesting a weaker association between the
      self and anger, but there were no age differences in the implicit sadness test,
      suggesting age-invariant associations between the self and sadness. Together
      these findings suggest multidirectional age differences in negative affect and
      the usefulness of a discrete emotions approach for research interested in
      emotional aging.

PMID- 24660794
TI  - Positive and negative social exchanges and cognitive aging in young-old adults:
      differential associations across family, friend, and spouse domains.
AB  - We examined how positive and negative social exchanges with friends, family, and
      spouses were related to cognitive aging in episodic and working memory, and
      perceptual speed. To do so, we used a large sample of cognitively intact young
      old participants from the PATH Through Life Study (PATH; aged 60 to 64 years at
      baseline, n = 1,618) who were assessed on 3 occasions over 8 years. Additional
      replication analyses were conducted using the Health and Retirement Study (HRS),
      which provided data on episodic memory. The main analysis of PATH Through Life
      showed that positive exchanges with friends and family were associated with less
      decline in perceptual speed, with these associations attenuated by adjustment for
      physical functioning and depressive symptoms. Negative exchanges with spouses
      were associated with poorer working memory performance. Positive exchanges with
      friends were associated with better initial episodic memory in both PATH and HRS.
      More frequent negative exchanges with friends and family were associated with
      better episodic memory in the PATH sample. However, these findings were not
      replicated in HRS. Our findings provide indirect support for the role of social
      exchange quality in contributing to cognitive enrichment. However, the
      inconsistent pattern of results across cognitive and social exchange domains
      points to possibilities of reverse causality, and may also indicate that social
      exchange quality plays a less important role for cognitive enrichment than other
      psychosocial characteristics.

PMID- 24660795
TI  - Trajectories of terminal decline in the well-being of older women: the DYNOPTA
      project.
AB  - Terminal decline in well-being is well established. However, the examination of
      covarying physical health and functioning on mortality-related well-being decline
      is limited. This study tested the effect of physical health changes on mortality
      related well-being decline and examined the extent to which mortality-related
      trajectories of different well-being dimensions are similar. Participants
      comprised 1,862 decedent Australian females (aged M = 69.59 years; SD = 8.08
      years at baseline) from the Dynamic Analyses to Optimize Ageing (DYNOPTA) Study
      who were observed on up to 4 occasions for up to 16 years (M = 6.04 years; SD =
      2.14 years) prior to death, and who provided data on 2 well-being indices,
      vitality and mental health. Although between and within-person change in physical
      health fully accounted for mortality-related well-being decline, further analysis
      indicated that prior level of physical health reported only small effects on
      subsequent level of well-being and was wholly unrelated to well-being change.
      Conversely, only prior vitality reported significant effects on the level of, and
      change in, physical health. In conclusion, terminal decline in vitality and
      mental health appears to be an artifact of within-person physical health change
      and not prior level of physical health. Future areas of research should focus on
      identifying other significant predictors of physical health change which
      subsequently impact on well-being decline. There is also a need to discriminate
      between different indices of well-being as mortality-related changes and
      associations with physical function are not consistent.

PMID- 24660796
TI  - Do hassles and uplifts change with age? Longitudinal findings from the VA
      normative aging study.
AB  - To examine emotion regulation in later life, we contrasted the modified hedonic
      treadmill theory with developmental theories, using hassles and uplifts to assess
      emotion regulation in context. The sample was 1,315 men from the VA Normative
      Aging Study aged 53 to 85 years, who completed 3,894 observations between 1989
      and 2004. We computed 3 scores for both hassles and uplifts: intensity (ratings
      reflecting appraisal processes), exposure (count), and summary (total) scores.
      Growth curves over age showed marked differences in trajectory patterns for
      intensity and exposure scores. Although exposure to hassles and uplifts decreased
      in later life, intensity scores increased. Group-based modeling showed individual
      differences in patterns of hassles and uplifts intensity and exposure, with
      relative stability in uplifts intensity, normative nonlinear changes in hassles
      intensity, and complex patterns of individual differences in exposure for both
      hassles and uplifts. Analyses with the summary scores showed that emotion
      regulation in later life is a function of both developmental change and
      contextual exposure, with different patterns emerging for hassles and uplifts.
      Thus, support was found for both hedonic treadmill and developmental change
      theories, reflecting different aspects of emotion regulation in late life.

PMID- 24660797
TI  - Reactivity to stressor pile-up in adulthood: effects on daily negative and
      positive affect.
AB  - This study used data from a 30-day diary study with 289 adults (age range 18-89
      years) to model the effects of stressor pile-up on individuals' daily negative
      affect (NA) and positive affect (PA) and to test for age differences in these
      effects. Specifically, we developed a new approach to operationalize and model
      stressor pile-up and evaluated this approach using generalized mixed models,
      taking into account the gamma response distribution of the highly skewed daily NA
      data. Findings showed that pile-up of stressors over a 1-week period was
      significantly coupled with increases in individuals' daily NA above and beyond
      the effect of concurrent stressors. Findings also showed that the effects of
      stressor accumulation and concurrent stress were additive rather than
      multiplicative. Age interacted significantly with stressor accumulation so that a
      higher age was associated with less NA reactivity to stressor pile-up. Yet, we
      did not find such an age-related association for NA reactivity to concurrent
      daily stressors. Daily PA was not associated with daily stress or with stressor
      pile-up. The operational definition of stressor pile-up presented in this study
      contributes to the literature by providing a new approach to model the dynamic
      effects of stress, and by providing new ways of separating the effects of acute
      stressors from the effects of stressor pile-up. The age differences found in the
      present study suggest that older adults develop effective emotion regulation
      skills for handling stressor pile-up, but that they react to acute daily
      stressors in a similar way than younger adults.

PMID- 24660799
TI  - Leisure sports and postural control: can a black belt protect your balance from
      aging?
AB  - To determine potential benefits of intensive leisure sports for age-related
      changes in postural control, we tested 3 activity groups comprising 70 young (M =
      21.67 years, SD = 2.80) and 73 older (M = 62.60 years, SD = 5.19) men. Activity
      groups were martial artists, who held at least 1st Dan (black belt), sportive
      individuals exercising sports without explicit balance components, and
      nonsportive controls. Martial artists had an advantage over sportive individuals
      in dynamic posture tasks (upright stance on a sway-referenced platform), and
      these 2 active groups showed better postural control than nonsportive
      participants. Age-related differences in postural control were larger in
      nonsportive men compared with the 2 active groups, who were similar in this
      respect. In contrast, negative age differences in other sensorimotor and
      cognitive functions did not differ between activity groups. We concluded that
      individuals engaging in intensive recreational sports have long-term advantages
      in postural control. However, even in older martial artists with years of
      practice in their sports, we observed considerable differences favoring the
      young.

PMID- 24660798
TI  - The cost of social punishment and high-lethality suicide attempts in the second
      half of life.
AB  - Age-related cognitive changes may contribute to impairments in making complex
      social decisions. Interpersonal conflict is a key factor behind suicidal behavior
      in old age, with suicidal motivations ranging from escape to revenge. Such
      conflicts may prove catastrophic for people prone to suicide, in part because of
      their tendency to make disadvantageous decisions. Yet, little is known about
      social decision making in older suicidal individuals. We assessed economic
      bargaining behavior using the Ultimatum Game, where players decide whether to
      accept or punish (reject) unfair monetary offers from another player. Our sample
      included depressed older adults with a history of high-medical-lethality suicide
      attempts, low-medical-lethality suicide attempts, nonsuicidal depressed older
      adults, and those with no psychiatric history who served as control groups.
      Participants in all groups punished their counterparts in response to unfair
      offers. However, low-lethality attempters, nonsuicidal depressed, and
      nonpsychiatric controls punished less as the cost of punishment increased,
      accepting more unfair offers as the stakes grew large. High-lethality attempters
      did not adjust their choices based on stake magnitude, punishing unfair offers
      without regard to the cost. Two thirds of the difference between the high
      lethality attempters and nonpsychiatric controls was explained by individual
      differences in fairness judgments: the comparison group judged offer fairness as
      a joint function of inequality and magnitude, whereas the high-lethality
      attempter participants judged offer fairness on the basis of inequality. In real
      life, high-lethality attempters' relative insensitivity to the cost of
      retaliation may lead to uncompromising, catastrophic responses to conflict.

PMID- 24660800
TI  - Outside of the laboratory: Associations of working-memory performance with
      psychological and physiological arousal vary with age.
AB  - We investigated age differences in associations among self-reported experiences
      of tense and energetic arousal, physiological activation indicated by heart rate,
      and working-memory performance in everyday life. The sample comprised 92
      participants aged 14-83 years. Data were collected for 24 hr while participants
      pursued their normal daily routines. Participants wore an ambulatory
      biomonitoring system that recorded their cardiac and physical activity. Using
      mobile phones as assessment devices, they also provided an average of 7
      assessments of their momentary experiences of tense arousal (feeling nervous) and
      energetic arousal (feeling wide-awake) and completed 2 trials of a well-practiced
      working-memory task. Experiences of higher energetic arousal were associated with
      higher heart rate in participants younger than 50 years of age but not in
      participants older than that, and energetic arousal was unrelated to within
      person fluctuations in working-memory performance. Experiences of tense arousal
      were associated with higher heart rate independent of participants' age. Tense
      arousal and physiological activation were accompanied by momentary impairments in
      working-memory performance in middle-aged and older adults but not in younger
      individuals. Results suggest that psychological arousal experiences are
      associated with lower working-memory performance in middle-aged and older adults
      when they are accompanied by increased physiological activation and that the same
      is true for physiological activation deriving from other influences. Hence, age
      differences in cognitive performance may be exaggerated when the assessment
      situation itself elicits tense arousal or occurs in situations with higher
      physiological arousal arising from affective experiences, physical activity, or
      circadian rhythms.

PMID- 24660801
TI  - Selective voluntary forgetting in young and older adults.
AB  - Aging is thought to involve a decline in executive-control capacities, although
      evidence regarding this claim is not always clear. Thus, although studies exist
      that suggest impoverished inhibitory memory control in older adults relative to
      younger adults, experiments with the list-method direct forgetting procedure have
      mostly failed to show adult-age differences in voluntary forgetting. In the
      present study we aimed to further study this issue by comparing young-old and
      young adults' performance with the selective directed forgetting (SDF) procedure,
      which we assumed to involve higher demands of executive control than the standard
      nonselective procedure. Thus, on the basis of previous studies showing that a
      critical factor in finding adult-age differences in executive-control tasks is
      the overall challenge posed by the tasks, we predicted less SDF in older adults
      than in younger adults. Supporting our hypothesis, across three experiments we
      show evidence of older adults' impoverished capacity to voluntarily forget
      episodic memories, although only when the task requires selective forgetting.
      Ours join other findings to suggest that sensitiveness to detect adult-age
      differences in cognitive control may strongly depend on the executive-control
      demands imposed by tasks.

PMID- 24660802
TI  - Age differences in short-term memory binding are related to working memory
      performance across the lifespan.
AB  - Memory performance increases during childhood and adolescence, and decreases in
      old age. Among younger adults, better ability to bind items to the context in
      which they were experienced is associated with higher working memory performance
      (Oberauer, 2005). Here, we examined the extent to which age differences in
      binding contribute to life span age differences in short-term memory (STM).
      Younger children (N = 85; 10 to 12 years), teenagers (N = 41; 13 to 15 years),
      younger adults (N = 84; 20 to 25 years), and older adults (N = 86; 70 to 75
      years) worked on global and local short-term recognition tasks that are assumed
      to measure item and item-context memory, respectively. Structural equation models
      showed that item-context bindings are functioning less well in children and older
      adults compared with younger adults and teenagers. This result suggests
      protracted development of the ability to form and recollect detailed short-term
      memories, and decline of this ability in aging. Across all age groups, better
      item-context binding was associated with higher working memory performance,
      indicating that developmental differences in binding mechanisms are closely
      related to working memory development in childhood and old age.

PMID- 24660803
TI  - Phoneme categorization and discrimination in younger and older adults: a
      comparative analysis of perceptual, lexical, and attentional factors.
AB  - This study investigates the extent to which age-related language processing
      difficulties are due to a decline in sensory processes or to a deterioration of
      cognitive factors, specifically, attentional control. Two facets of attentional
      control were examined: inhibition of irrelevant information and divided
      attention. Younger and older adults were asked to categorize the initial phoneme
      of spoken syllables ("Was it m or n?"), trying to ignore the lexical status of
      the syllables. The phonemes were manipulated to range in eight steps from m to n.
      Participants also did a discrimination task on syllable pairs ("Were the initial
      sounds the same or different?"). Categorization and discrimination were performed
      under either divided attention (concurrent visual-search task) or focused
      attention (no visual task). The results showed that even when the younger and
      older adults were matched on their discrimination scores: (1) the older adults
      had more difficulty inhibiting lexical knowledge than did younger adults, (2)
      divided attention weakened lexical inhibition in both younger and older adults,
      and (3) divided attention impaired sound discrimination more in older than
      younger listeners. The results confirm the independent and combined contribution
      of sensory decline and deficit in attentional control to language processing
      difficulties associated with aging. The relative weight of these variables and
      their mechanisms of action are discussed in the context of theories of aging and
      language.

PMID- 24660805
TI  - Erectile dysfunction, vascular risk, and cognitive performance in late middle
      age.
AB  - Vascular disease is the most common etiology of erectile dysfunction (ED). Men
      with ED are at a 65% increased relative risk of developing coronary heart disease
      and a 43% increased risk of stroke within 10 years. Vascular disease is
      associated with cognitive impairment; ED-an overt manifestation of vascular
      dysfunction-could also signal early compromised cognition. We sought to determine
      whether cognitive differences existed between men with ED and healthy peers. Our
      sample consisted of 651 men (ages 51-60 years) from the Vietnam Era Twin Study of
      Aging. ED was associated with poorer cognitive performance, particularly on
      attention-executive-psychomotor speed tasks. ED remained significantly associated
      with cognition after inclusion of other cardiovascular risk factors (including
      hypertension, high cholesterol, body mass index, and smoking). These findings
      underscore the importance of further study of ED as a predictor of cognitive and
      cardiovascular health. (PsycINFO Database Record (c) 2014 APA, all rights
      reserved). 

PMID- 24660807
TI  - Strain analysis during exercise in patients with asymptomatic atrial septal
      defect.
AB  - BACKGROUND: Right ventricular (RV) deformational mechanics have been demonstrated
      in patients with atrial septal defect (ASD) at rest, but there is lack of
      information on their adaptation to exercise. The aim of this study was to assess
      the adaptability of RV strains and strain rates (SRs) during exercise in patients
      with clinically asymptomatic ASD. METHODS: Twenty patients with asymptomatic ASD
      and 11 age-matched controls were included. All the subjects performed incremental
      ergometry and underwent standard echocardiography and two-dimensional strain (S)
      and SR imaging by speckle tracking at rest and during submaximal exercise.
      RESULTS: There was no significant difference in RV strains and SRs at rest
      between the controls and the ASD patients. There was a significant elevation in
      the strains and SRs of both groups with exercise. However, the lateral and septal
      strains increased significantly higher than the controls in patients with ASD.
      But there was no significant difference in SRs during exercise in both of the
      groups. CONCLUSIONS: Asymptomatic ASD patients without RV overload, have same
      strain and SR results at rest with the controls, however, these findings worsen
      during submaximal exercise, when compared to the controls.

PMID- 24660808
TI  - Aggressiveness in familial nonmedullary thyroid carcinoma--the controversy
      continues.

PMID- 24660809
TI  - Bioactive surface design based on functional composite electrospun nanofibers for
      biomolecule immobilization and biosensor applications.
AB  - The combination of nanomaterials and conducting polymers attracted remarkable
      attention for development of new immobilization matrices for enzymes. Hereby, an
      efficient surface design was investigated by modifying the graphite rod electrode
      surfaces with one-step electrospun nylon 6,6 nanofibers or 4% (w/w) multiwalled
      carbon nanotubes (MWCNTs) incorporating nylon 6,6 nanofibers (nylon 6,6/4MWCNT).
      High-resolution transmission electron microscopy study confirmed the successful
      incorporation of the MWCNTs into the nanofiber matrix for nylon 6,6/4MWCNT
      sample. Then, these nanofibrous surfaces were coated with a conducting polymer,
      (poly-4-(4,7-di(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)benzaldehyde) (PBIBA) to
      obtain a high electroactive surface area as new functional immobilization
      matrices. Due to the free aldehyde groups of the polymeric structures, a model
      enzyme, glucose oxidase was efficiently immobilized to the modified surfaces via
      covalent binding. Scanning electron microscope images confirmed that the
      nanofibrous structures were protected after the electrodeposition step of PBIBA
      and a high amount of protein attachment was successfully achieved by the help of
      high surface to volume ratio of electroactive nanofiber matrices. The biosensors
      were characterized in terms of their operational and storage stabilities and
      kinetic parameters (K(m)(app) and Imax). The resulting novel glucose biosensors
      revealed good stability and promising Imax values (10.03 and 16.67 MUA for nylon
      6,6/PBIBA and nylon 6,6/4MWCNT/PBIBA modified biosensors, respectively) and long
      shelf life (32 and 44 days for nylon 6,6/PBIBA and nylon 6,6/4MWCNT/PBIBA
      modified biosensors, respectively). Finally, the biosensor was tested on
      beverages for glucose detection.

PMID- 24660806
TI  - Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65.
AB  - We have previously reported that the Parkinson's disease-associated kinase PINK1
      (PTEN-induced putative kinase 1) is activated by mitochondrial depolarization and
      stimulates the Parkin E3 ligase by phosphorylating Ser65 within its Ubl
      (ubiquitin-like) domain. Using phosphoproteomic analysis, we identified a novel
      ubiquitin phosphopeptide phosphorylated at Ser65 that was enriched 14-fold in HEK
      (human embryonic kidney)-293 cells overexpressing wild-type PINK1 stimulated with
      the mitochondrial uncoupling agent CCCP (carbonyl cyanide m
      chlorophenylhydrazone), to activate PINK1, compared with cells expressing kinase
      inactive PINK1. Ser65 in ubiquitin lies in a similar motif to Ser65 in the Ubl
      domain of Parkin. Remarkably, PINK1 directly phosphorylates Ser65 of ubiquitin in
      vitro. We undertook a series of experiments that provide striking evidence that
      Ser65-phosphorylated ubiquitin (ubiquitinPhospho-Ser65) functions as a critical
      activator of Parkin. First, we demonstrate that a fragment of Parkin lacking the
      Ubl domain encompassing Ser65 (DeltaUbl-Parkin) is robustly activated by
      ubiquitinPhospho-Ser65, but not by non-phosphorylated ubiquitin. Secondly, we
      find that the isolated Parkin Ubl domain phosphorylated at Ser65 (UblPhospho
      Ser65) can also activate DeltaUbl-Parkin similarly to ubiquitinPhospho-Ser65.
      Thirdly, we establish that ubiquitinPhospho-Ser65, but not non-phosphorylated
      ubiquitin or UblPhospho-Ser65, activates full-length wild-type Parkin as well as
      the non-phosphorylatable S65A Parkin mutant. Fourthly, we provide evidence that
      optimal activation of full-length Parkin E3 ligase is dependent on PINK1-mediated
      phosphorylation of both Parkin at Ser65 and ubiquitin at Ser65, since only
      mutation of both proteins at Ser65 completely abolishes Parkin activation. In
      conclusion, the findings of the present study reveal that PINK1 controls Parkin
      E3 ligase activity not only by phosphorylating Parkin at Ser65, but also by
      phosphorylating ubiquitin at Ser65. We propose that phosphorylation of Parkin at
      Ser65 serves to prime the E3 ligase enzyme for activation by ubiquitinPhospho
      Ser65, suggesting that small molecules that mimic ubiquitinPhospho-Ser65 could
      hold promise as novel therapies for Parkinson's disease. 

PMID- 24660810
TI  - Combining mass spectrometry diagnostic and density functional theory calculations
      for a better understanding of the plasma polymerization of ethyl lactate.
AB  - The focus of this work is on the growth mechanism of ethyl lactate-based plasma
      polymer film (ELPPF) that could be used as barrier coatings. In such an
      application, the ester density of the plasma polymer has to be controlled to tune
      the degradation rate of the material. Our strategy consists of correlating the
      plasma chemistry evaluated by RGA mass spectrometry and understanding, via DFT
      calculations, the chemistry of the synthesized thin films. The theoretical
      calculations helped us to understand the plasma chemistry in plasma ON and OFF
      conditions. From these data it is unambiguously shown that the signal m/z 75 can
      directly be correlated with the precursor density in the plasma phase. The
      combination of XPS and chemical derivatization experiments reveal that the ester
      content in the ELPFF can be tailored from 2 to 18 at. % by decreasing the RF
      power, which is perfectly correlated with the evolution of the plasma chemistry.
      Our results also highlight that the ELPPF chemistry, especially the ester
      content, is affected by the plasma mode of operation (continuous or pulsed
      discharge, at similar injected mean power) for similar ester content in the
      plasma. This could be related to different energy conditions at the interface of
      the growing films that could affect the sticking coefficient of the ester-bearing
      fragments. 

PMID- 24660811
TI  - Characterization of scale-dependent dispersivity in fractured formations through
      a divergent flow tracer test.
AB  - Scale-dependency of dispersivity has been reported from field tracer tests. We
      present a simple methodology for characterization of dispersivity as a linear
      function of scale around an injection well using divergent flow tracer test data
      conducted in fractured formations. Results show that the slope of this linear
      dispersivity function can be estimated using tracer concentration measurements in
      a monitoring well. The characterized dispersivity function has applications in
      modeling of field-scale transport processes in fractured formations. 

PMID- 24660813
TI  - Early frontalis flap surgery as first option to correct congenital ptosis with
      poor levator function.
AB  - In congenital blepharoptosis the upper eyelid cannot be lifted normally because
      of congenital impairment in the levator function. The descended eyelid margin
      partially or completely obstructs of the visual axis with the consequent risk of
      amblyopia. Frontalis suspension is the surgery of choice for ptosis with poor
      levator function creating a linkage between the frontalis muscle and the tarsus;
      the frontalis muscle is used to elevate the eyelid. Direct transplantation of
      frontalis muscle to the upper eyelid has been widely described. We report our
      experience using frontalis flap in congenital ptosis with poor levator function
      in children. METHODS: Retrospective study of 30 eyes with severe congenital
      ptosis and poor levator function treated by means of direct frontalis flap. Mean
      age 2 years. Eyelid measurements were taken at baseline, 1, 3, 12 months
      postoperatively and last visit. Mean ptosis degree was 5 mm (3-8 mm) and levator
      function 2 mm (1-5 mm). The presence of complications, flap function and
      palpebral contour were evaluated. Mean follow up time was 27 months. At last
      visit, ptosis degree ranged from 0 to 3 mm. DISCUSSION: Direct advancement of the
      frontalis muscle to treat severe eyelid ptosis is effective and stable in the
      long term avoiding the use of a linking structure, therefore the risk of foreign
      body reaction, absorption, granuloma and late exposure, as well as the need for a
      second visible incision in the forehead. Patients learn how to control the lid
      height by means of the frontalis muscle achieving more symmetry.

PMID- 24660812
TI  - Improved total synthesis and biological evaluation of potent apratoxin S4 based
      anticancer agents with differential stability and further enhanced activity.
AB  - Apratoxins are cytotoxic natural products originally isolated from marine
      cyanobacteria that act by preventing cotranslational translocation early in the
      secretory pathway to downregulate receptor levels and inhibit growth factor
      secretion, leading to potent antiproliferative activity. Through rational design
      and total synthesis of an apratoxin A/E hybrid, apratoxin S4 (1a), we have
      previously improved the antitumor activity and tolerability in vivo. Compound 1a
      and newly designed analogues apratoxins S7-S9 (1b-d), with various degrees of
      methylation at C34 (1b,c) or epimeric configuration at C30 (1d), were efficiently
      synthesized utilizing improved procedures. Optimizations have been applied to the
      synthesis of key intermediate aldehyde 7 and further include the application of
      Leighton's silanes and modifications of Kelly's methods to induce thiazoline ring
      formation in other crucial steps of the apratoxin synthesis. Apratoxin S9 (1d)
      exhibited increased activity with subnanomolar potency. Apratoxin S8 (1c) lacks
      the propensity to be deactivated by dehydration and showed efficacy in a human
      HCT116 xenograft mouse model. 

PMID- 24660814
TI  - How we handle appeals and why.

PMID- 24660816
TI  - Of molecules, medicine, and Google Glass.
AB  - A compelling area of use for Google Glass, a new computing and communication
      platform in the form of a network-connected head-worn system, is in laboratory
      experimentation and medicine. In the current issue of ACS Nano, Ozcan and
      colleagues describe how Google Glass can be used to automatically identify the
      results of immuno-assays. This and other recent pioneering works point toward the
      utility of the platform in aiding and augmenting the experience of laboratory
      scientists and physicians by enabling on-the-go access to information, seamless
      recording and documentation, live sharing of points of view, and eventually
      augmented reality. 

PMID- 24660817
TI  - Precision nanomedicine in neurodegenerative diseases.
AB  - The treatment of neurodegenerative diseases remains a tremendous challenge due to
      the limited access of molecules across the blood-brain barrier, especially large
      molecules such as peptides and proteins. As a result, at most, a small percentage
      of a drug that is administered systemically will reach the central nervous system
      in its active form. Currently, research in the field focuses on developing safer
      and more effective approaches to deliver peptides and proteins into the central
      nervous system. Multiple strategies have been developed for this purpose.
      However, noninvasive approaches, such as nanostructured protein delivery carriers
      and intranasal administration, seem to be the most promising strategies for the
      treatment of chronic diseases, which require long-term interventions. These
      approaches are both target-specific and able to rapidly bypass the blood-brain
      barrier. In this Perspective, we detail some of these strategies and discuss some
      of the potential pitfalls and opportunities in this field. The next generation
      strategies will most likely be more cell-type-specific. Devising these strategies
      to target the brain may ultimately become a novel therapeutic modality to treat
      neurodegenerative diseases. 

PMID- 24660818
TI  - Comment on "amine-modified graphene: thrombo-protective safer alternative to
      graphene oxide for biomedical applications".

PMID- 24660819
TI  - Comment on "insight into organometallic intermediate and its evolution to
      covalent bonding in surface-confined Ullmann polymerization".

PMID- 24660820
TI  - Reply to "comment on 'insight into organometallic intermediate and its evolution
      to covalent bonding in surface-confined Ullmann polymerization'".

PMID- 24660822
TI  - Stereocontrolled total synthesis of hedyotol A.
AB  - The total synthesis of hedyotol A (1), a natural product isolated from Hedyotis
      lawsoniae (DC.) Wight et Arn. (Rubiaceae), was accomplished in a highly
      stereocontrolled manner. Key steps include an L-proline-catalyzed cross-aldol
      reaction and the biomimetic construction of a furofuran lignan skeleton through a
      quinomethide intermediate.

PMID- 24660823
TI  - IL28B rs 12979860 predicts response to treatment in Egyptian hepatitis C virus
      genotype 4 patients and alpha fetoprotein increases its predictive strength.
AB  - To assess the role of IL28B rs 12979860 polymorphism in predicting response to
      treatment in genotype 4 (G4) Egyptian patients, and to evaluate the role of alpha
      fetoprotein (AFP) in increasing the predictive strength of IL28B rs 12979860
      polymorphism to predict response to treatment. One hundred thirty 7 HCV patients
      were genotyped for IL28B rs 12979860 by polymerase chain reaction--restriction
      fragment length polymorphism technique. The presence of the C allele of IL28B rs
      12979860 was associated with response to treatment, while the T allele was
      associated with failure of response to treatment. AFP is associated with IL28B rs
      12979860 SNP genotypes at cut off 2.68 and 4.5 ng/mL individually. Response rate
      was 1.3 and 1.6, 3 times higher in CC, CT, and TT respectively in patients below
      AFP 4.5 ng/mL than in patients above it. IL28B rs 12979860 polymorphism is
      strongly associated with treatment induced response to treatment. AFP (cut off
      4.5 mg/mL) increases the predictive power of IL28B in response to treatment.

PMID- 24660825
TI  - Bone marrow examination in patients with immune thrombocytopenia: is there
      anything different in older patients?
AB  - Immune thrombocytopenia (ITP) is a disorder characterised by immune-mediated
      accelerated platelet destruction and suppressed platelet production. In the bone
      marrow examinations of patients with ITP, some investigators found megakaryocyte
      numbers to be increased while others have found them to be normal. Although
      recent guidelines recommend against bone marrow examinations in typical ITP
      patients, the recent introduction of thrombopoietin receptor agonists as an
      effective treatment for ITP has refocused attention on abnormalities of bone
      marrow megakaryocytes. In this study, we retrospectively analysed the bone marrow
      aspiration, flow cytometry-CD45 side scatter (SSC) and biopsy results of our
      patients with ITP by dividing them into two groups according to age (<60 yr and
      >=60 yr). Ninety eight newly diagnosed ITP patients were included in the study.
      CD45 SSC results were recorded as percentages of normoblasts, granulocytes,
      lymphocytes, monocytes and myeloid/erythroid ratio. Length of the biopsy
      specimen, cellularity, presence of dysplasia or fibrosis with number, morphology
      and distribution of megakaryocytes were recorded. In group 1, there were 49
      patients. Mean age was 41.31 +/- 12.77 yr. In group 2, there were 49 patients.
      Mean age was 70.78 +/- 7.88 yr. Megakaryocyte numbers on bone marrow aspirates
      were not recorded in most patients, so we could not comment on this point. Flow
      cytometry results and bone marrow findings were similar between two groups. In
      conclusion, there is no difference between bone marrow examinations of young and
      older patients with ITP, and biopsy should not be recommended in typical ITP
      patients as already mentioned in guidelines.

PMID- 24660826
TI  - Differences in methodological quality between positive and negative published
      clinical trials.
AB  - AIM: Comparison of methodological quality differences in nursing clinical trials
      with positive and negative findings. BACKGROUND: The growth of nursing
      publications and increased reliance on data to guide clinical care make
      publication quality assessment imperative. One major concern is the tendency for
      more studies with positive findings to be published, potentially resulting in the
      publication of lower quality trials. DESIGN: Secondary analysis of published
      trials to compare studies with positive and negative findings in terms of
      clinical trial quality and sample size calculation methodology. DATA SOURCES:
      Twenty articles each from three major nursing journals (Journal of Clinical
      Nursing, Journal of Advanced Nursing and International Journal of Nursing
      Studies) for the years 2010-2012. We assessed article quality in terms of Jadad
      scores, methods and total sample size. IMPLICATIONS FOR NURSING: This article
      underscores the importance of nurses and nursing students having the ability to
      assess the quality of published trials, so that they can make appropriate
      judgments on the implementation of care for patients as the use of evidence-based
      practice increases. CONCLUSION: Potential differences in methodological quality
      between positive and negative trials may lead to positive trials with biased
      results, or discrimination against negative trials. The CONSORT is recommended,
      but use is still limited. Therefore, it is important to reinforce the use of
      these guidelines to supply readers with information on the quality of the
      published trials. The combination of authors publishing higher quality trials and
      deeper reader knowledge of quality assessment can have important clinical
      consequences.

PMID- 24660827
TI  - Effects of benzalkonium chloride on the blood-aqueous and blood-retinal barriers
      of pseudophakic eyes.
AB  - PURPOSE: To evaluate the effects of benzalkonium chloride (BAK) on the blood
      aqueous (BAB) and blood-retinal barriers (BRB) of pseudophakic eyes. METHODS:
      Prospective, randomized, investigator-masked, comparative study. Patients were
      randomly assigned to preservative-free artificial tears or BAK-preserved
      artificial tears. One drop of artificial tears was instilled 4 times a day in the
      study eye, starting the day after randomization for 30 days. Anterior chamber
      flare was assessed by a laser flare meter (LFM) and macular thickness
      measurements were obtained with optical coherence tomography, before, 15, and 30
      days after randomization. RESULTS: A total of 44 healthy eyes of 44 pseudophakic
      volunteers were recruited. There were no significant differences regarding
      demographics (age, gender, and race distributions) and clinical characteristics
      (eye, mean intraocular pressure, and mean best-corrected visual acuity) between
      the 2 groups (P>0.05). No significant differences in baseline mean LFM values
      were observed (P=0.262). However, we detected a statistically significant
      increase in mean LFM measurements in the BAK-preserved group (11.4 +/- 5.1 ph/ms)
      (P=0.017) after 15 days. After 30 days, the BAK-preserved group maintained
      significantly higher flare values (11.9 +/- 5.9 ph/ms) compared with baseline
      (P=0.043). On the other hand, the preservative-free group showed mean flare
      values of 8.4 +/- 2.5 ph/ms, not significantly different from those obtained at
      baseline (P=1.00). We observed no statistically significant change in macular
      thickness measurements at days 15 and 30 in either group (P>0.05). Cystoid
      macular edema was not detected in this series. CONCLUSIONS: Our results suggest
      that a short-term exposure to BAK can cause disruption of the BAB, without
      altering the BRB in pseudophakic eyes.

PMID- 24660828
TI  - Photoresponsive block copolymer: synthesis, characterization, and surface
      activity control.
AB  - Amphiphilic block copolymers bearing chromophores are used to achieve
      photoresponses upon exposure to suitable light, which alter molecular properties,
      but the photostimulus surface activity control of amphiphilic block copolymers
      remains to be elucidated. In this work, a series of novel amphiphilic block
      copolymers consisting of a carboxymethyl betaine monomer (called GLBT) and 4
      ethoxy-4'-methacrylamide (EMAAB) with different block ratios have been
      synthesized using a reversible addition-fragmentation chain-transfer (RAFT)
      polymerization process. Copolymers were observed to be self-assembled in the
      aqueous solution above a critical micelle concentration, which was determined by
      static light scattering measurements and formed vesicles of 120-170 nm in
      diameter, at different pH values. Copolymers were found to be surface-active at
      pH 7 but exhibited non-surface activity at acidic and alkaline pH values. After
      being irradiated with 360 nm UV light, copolymers showed a significant
      photoresponse both at the surface and in bulk solution as a result of the
      photoinduced isomerization of azochromophores. The surface property of copolymers
      was significantly affected by UV irradiation at pH 7, and block copolymers became
      non-surface-active. The bulk properties changed considerably upon UV exposure
      where polymer vesicles transformed to micelles as a result of the polarity
      difference between two azo isomers (cis and trans isomers). All of these
      transitions were found to be reversible. A new method to control the surface
      active/nonactive and vesicle/micelle transitions by light and pH has been
      established by introducing an azobenzene chromophore and GLBT into amphiphlic
      diblock copolymers. 

PMID- 24660830
TI  - Site-specific chemical labeling of mitochondrial respiratory complex I through
      ligand-directed tosylate chemistry.
AB  - The site-specific chemical modification of NADH-quinone oxidoreductase (complex
      I) by various functional probes such as fluorophores and microbeads, without
      affecting the enzyme activity, may allow single-molecule analyses of putative
      dynamic conformational changes in the enzyme. In an attempt to address this
      challenge, we performed site-specific alkynylation of complex I in bovine heart
      submitochondrial particles by means of a ligand-directed tosylate (LDT) chemistry
      strategy with synthetic acetogenin ligand 1, which has an alkynylated tosylate in
      the tail moiety, as a high-affinity ligand against the enzyme. The terminal
      alkyne was chosen as the tag to be incorporated into the enzyme because this
      functional group can serve as a "footing" for subsequent diverse chemical
      modifications via so-called click chemistry (i.e., azide-alkyne [3+2]
      cycloaddition in water). To identify the position alkynylated by ligand 1,
      fluorescent tetramethylrhodamine was covalently attached to the incorporated
      alkyne by click chemistry after the solubilization of complex I. Detailed
      proteomic analyses revealed that alkynylation occurred at Asp160 in the 49 kDa
      subunit, which may be located in the inner part of the putative quinone-binding
      cavity. The alkynylation was completely suppressed in the presence of an excess
      of other inhibitors such as bullatacin and quinazoline. While the reaction yield
      of the alkynylation step via LDT chemistry was estimated to be ~50%, the
      alkynylation unfortunately resulted in the almost complete inhibition of enzyme
      activity. Nevertheless, the results of this study demonstrate that complex I can
      be site-specifically alkynylated through LDT chemistry, providing a clue about
      the diverse chemical modifications of the enzyme in combination with click
      chemistry.

PMID- 24660829
TI  - Revealing CD38 cellular localization using a cell permeable, mechanism-based
      fluorescent small-molecule probe.
AB  - Nicotinamide adenine dinucleotide (NAD) is increasingly recognized as an
      important signaling molecule that affects numerous biological pathways. Thus,
      enzymes that metabolize NAD can have important biological functions. One NAD
      metabolizing enzyme in mammals is CD38, a type II transmembrane protein that
      converts NAD primarily to adenosine diphosphate ribose (ADPR) and a small amount
      of cyclic adenosine diphosphate ribose (cADPR). Localization of CD38 was
      originally thought to be only on the plasma membrane, but later reports showed
      either significant or solely, intracellular CD38. With the efficient NAD
      hydrolysis activity, the intracellular CD38 may lead to depletion of cellular
      NAD, thus producing harmful effects. Therefore, the intracellular localization of
      CD38 needs to be carefully validated. Here, we report the synthesis and
      application of a cell permeable, fluorescent small molecule (SR101-F-araNMN) that
      can covalently label enzymatically active CD38 with minimal perturbation of live
      cells. Using this fluorescent probe, we revealed that CD38 is predominately on
      the plasma membrane of Raji and retinoic acid (RA)-treated HL-60 cells.
      Additionally, the probe revealed no CD38 expression in K562 cells, which was
      previously reported to have solely intracellular CD38. The finding that very
      little intracellular CD38 exists in these cell lines suggests that the major
      enzymatic function of CD38 is to hydrolyze extracellular rather than
      intracellular NAD. The fluorescent activity-based probes that we developed allow
      the localization of CD38 in different cells to be determined, thus enabling a
      better understanding of the physiological function. 

PMID- 24660831
TI  - The FACIT-Sp spiritual well-being scale: an investigation of the dimensionality,
      reliability and construct validity in a cognitively intact nursing home
      population.
AB  - BACKGROUND: Spiritual well-being has been found to be a strong individual
      predictor of overall nursing home satisfaction and a fundamental dimension of
      global as well as health-related quality-in-life among nursing home patients.
      Therefore, access to a valid and reliable measure of spiritual well-being among
      nursing home patients is highly warranted. OBJECTIVES: The aim of this study was
      to investigate the dimensionality, reliability and construct validity of the
      Functional Assessment of Chronic Illness Therapy Spiritual Wellbeing scale in a
      cognitively intact nursing home population. DESIGN AND METHOD: A cross-sectional
      design was applied, selecting two counties in central Norway from which 20
      municipalities representing 44 different nursing homes took part in this study.
      Long-term care was defined as 24-hour care with duration of 6 months or longer.
      Participants were 202 cognitively intact long-term nursing home patients
      fulfilling the inclusion criteria. Approval by all regulatory institutions
      dealing with research issues in Norway and the Management Unit at the 44 nursing
      homes was obtained. Explorative and confirmative factor analyses as well as
      correlation with selected construct were used. RESULTS: Though three items loaded
      very low (lambda = 0.22, 0.26, 0.32) indicating low reliability, the three-factor
      model for the FACIT-Sp spiritual well-being scale provided an acceptable fit
      (chi(2) = 101.15 (df = 50), p-value <0.001, RMSEA = 0.075 p = 0.030, NFI = 0.90,
      GFI = 0.91, AGFI = 0.85) for older nursing home patients, demonstrating
      acceptable measurement reliability. Construct validity was supported by
      significant correlations in the hypothesised direction with the selected
      constructs. CONCLUSION: The three-factor model is an improvement over the
      original two-factor construct, based on these nursing home data. The measure
      yielded significantly factor loadings, good composite reliability and construct
      validity.

PMID- 24660832
TI  - Evaluation of conventional nonpulsatile and novel pulsatile extracorporeal life
      support systems in a simulated pediatric extracorporeal life support model.
AB  - The objective of this study is to evaluate two extracorporeal life support (ECLS)
      circuits and determine the effect of pulsatile flow on pressure drop,
      flow/pressure waveforms, and hemodynamic energy levels in a pediatric
      pseudopatient. One ECLS circuit consisted of a Medos Deltastream DP3 diagonal
      pump and Hilite 2400 LT oxygenator with arterial/venous tubing. The second
      circuit consisted of a Maquet RotaFlow centrifugal pump and Quadrox-iD Pediatric
      oxygenator with arterial/venous tubing. A 14Fr Medtronic Bio-Medicus one-piece
      pediatric arterial cannula was used for both circuits. All trials were conducted
      at flow rates ranging from 500 to 2800 mL/min using pulsatile or nonpulsatile
      flow. The post-cannula pressure was maintained at 50 mm Hg. Blood temperature was
      maintained at 36 degrees C. Real-time pressure and flow data were recorded using
      a custom-based data acquisition system. The results showed that the Deltastream
      DP3 circuit produced surplus hemodynamic energy (SHE) in pulsatile mode at all
      flow rates, with greater SHE delivery at lower flow rates. Neither circuit
      produced SHE in nonpulsatile mode. The Deltastream DP3 pump also demonstrated
      consistently higher total hemodynamic energy at the pre-oxygenator site in
      pulsatile mode and a lesser pressure drop across the oxygenator. The Deltastream
      DP3 pump generated physiological pulsatility without backflow and provided
      increased hemodynamic energy. This novel ECLS circuit demonstrates suitable in
      vitro performance and adaptability to a wide range of pediatric patients. 

PMID- 24660833
TI  - Perioperative allogeneic nonleukoreduced blood transfusion and prostate cancer
      outcomes after radical prostatectomy.
AB  - BACKGROUND: Allogeneic blood transfusion induces immunosuppression, and concern
      has been raised that it may increase propensity for cancer recurrence; however,
      these effects have not been confirmed. We examined the association of
      perioperative transfusion of allogeneic blood long-term oncologic outcomes in
      patients with prostate cancer who underwent prostatectomy. STUDY DESIGN AND
      METHODS: We reviewed medical records of patients who underwent radical
      prostatectomy between 1991 and 2005 and received allogeneic nonleukoreduced
      blood. Each transfused patient was matched to two controls who did not receive
      blood: matching included age, surgical year, prostate-specific antigen level,
      pathologic tumor stages, pathologic Gleason scores, and anesthetic type. Primary
      outcome was systemic tumor progression, with secondary outcomes of prostate
      cancer death and all-cause mortality. Stratified proportional hazards regression
      analysis was used to assess differences in outcomes between the transfused and
      nontransfused group. RESULTS: A total of 379 prostatectomy patients who were
      transfused and 758 nontransfused controls were followed for 9.4 and 10.2 years
      (median), respectively. In a multivariable analysis that took into account the
      matched study design and adjusted for positive surgical margins and adjuvant
      therapies, the use of allogeneic blood was not associated with systemic tumor
      progression (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.39-1.99; p
      = 0.76), prostate cancer-specific death (HR, 1.69; 95% CI, 0.44 to 6.48; p =
      0.44), or all-cause death (HR, 1.20; 95% CI, 0.87 to 1.67; p = 0.27).
      CONCLUSIONS: When adjusted for clinicopathologic and procedural variables
      transfusion of allogeneic blood was not associated with systemic tumor
      progression and survival outcomes.

PMID- 24660834
TI  - Echocardiography-based hemodynamic management of left ventricular diastolic
      dysfunction: a feasibility and safety study.
AB  - BACKGROUND: Patients with left ventricular diastolic dysfunction (LVDD) are at
      increased risk of postoperative adverse events. The primary aim of this study was
      to evaluate the safety and feasibility of using echocardiography-guided
      hemodynamic management (EGHEM) during surgery in subjects with LVDD compared to
      conventional management. The feasibility of using echocardiography to direct a
      treatment algorithm and clinical outcomes were compared for safety between
      groups. METHODS: Subjects were screened for LVDD by preoperative transthoracic
      echocardiography (TTE) and randomized to the conventional or EGHEM group.
      Subjects in EGHEM received hemodynamic management based on left ventricular
      filling patterns on transesophageal echocardiography (TEE). Primary outcomes
      measured were the feasibility to obtain TEE images and follow a TEE-based
      treatment algorithm. Safety outcomes also compared the following clinical
      differences between groups: length of hospitalization, incidence of atrial
      fibrillation, congestive heart failure (CHF), myocardial infarction,
      cerebrovascular accident, transient ischemic attack and renal failure measured 30
      days postoperatively. RESULTS: Population consisted of 28 surgical subjects (14
      in conventional group and 14 in EGHEM group). Mean subject age was 73.4 +/- 6.7
      years (36% male) in conventional group and 65.9 +/- 14.4 years (36% male) in
      EGHEM group. Procedures included orthopedic (conventional = 29%, EGHEM 36%),
      general (conventional = 50%, EGHEM = 36%), vascular (conventional = 7%, EGHEM =
      21%), and thoracic (conventional = 14%, EGHEM = 7%). There was no statistically
      significant difference in adverse clinical events between the 2 groups. The EGHEM
      group had less CHF, atrial fibrillation, and shorter length of stay. CONCLUSIONS:
      Echocardiography-guided hemodynamic management of patients with LVDD during
      surgery is feasible and may be a safe alternative to conventional management.

PMID- 24660835
TI  - Terahertz vibrational modes of the rigid crystal phase of succinonitrile.
AB  - Succinonitrile (N = C-CH2-CH2-C = N), an orientationally disordered molecular
      plastic crystal at room temperature, exhibits rich phase behavior including a
      solid-solid phase transition at 238 K. In cooling through this phase transition,
      the high-temperature rotational disorder of the plastic crystal phase is frozen
      out, forming a rigid crystal that is both spatially and orientationally ordered.
      Using temperature-dependent terahertz time-domain spectroscopy, we characterize
      the vibrational modes of this low-temperature crystalline phase for frequencies
      from 0.3 to 2.7 THz and temperatures ranging from 20 to 220 K. Vibrational modes
      are observed at 1.122 and 2.33 THz at 90 K. These modes are assigned by solid
      state density functional theory simulations, corresponding respectively to the
      translation and rotation of the molecules along and about their crystallographic
      c-axis. In addition, we observe a suppression of the phonon modes as the
      concentration of dopants, in this case a lithium salt (LiTFSI), increases,
      indicating the importance of doping-induced disorder in these ionic conductors.

PMID- 24660836
TI  - Specimen-thickness effects on transmission Kikuchi patterns in the scanning
      electron microscope.
AB  - We report the effects of varying specimen thickness on the generation of
      transmission Kikuchi patterns in the scanning electron microscope. Diffraction
      patterns sufficient for automated indexing were observed from films spanning
      nearly three orders of magnitude in thickness in several materials, from 5 nm of
      hafnium dioxide to 3 MUm of aluminum, corresponding to a mass-thickness range of
      ~5 to 810 MUg cm(-2) . The scattering events that are most likely to be detected
      in transmission are shown to be very near the exit surface of the films. The
      energies, spatial distribution and trajectories of the electrons that are
      transmitted through the film and are collected by the detector are predicted
      using Monte Carlo simulations.

PMID- 24660837
TI  - Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis
      associated delirium in septic patients.
AB  - BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids
      in sepsis are conflicting. In this study, the effect of administration of
      parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis
      associated delirium, and inflammatory mediators in septic patients was
      investigated. METHODS: Fifty patients with sepsis were randomized to receive
      either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil
      (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to
      the intensive care unit or standard treatment. Markers of brain injury and
      inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis
      associated delirium was performed daily. The primary outcome was the difference
      in S-100beta from baseline to peak level between both the intervention and the
      control group, compared by t-test. Changes of all markers over time were explored
      in both groups, fitting a generalized estimating equations model. RESULTS: Mean
      difference in change of S-100beta from baseline to peak level was 0.34 (95% CI: 
      0.18-0.85) between the intervention and control group, respectively (P = 0.19).
      We found no difference in plasma levels of S-100beta, neuron-specific enolase,
      interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time.
      Incidence of sepsis-associated delirium was 75% in the intervention and 71% in
      the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION:
      Administration of n-3 fatty acids did not affect markers of brain injury,
      incidence of sepsis-associated delirium, and inflammatory mediators in septic
      patients.

PMID- 24660838
TI  - Diffusion Monte Carlo calculations of zero-point structures of partially
      deuterated isotopologues of H7(+).
AB  - Diffusion Monte Carlo calculations for all the deuterated H7(+) isotopologues and
      isotopomers were performed to determine their zero-point energies, and thus the
      stability of them. Based on these calculations, we conclude that the deuterium
      atom prefers the unbonded position in the central H3(+), and then the bonded
      position in H3(+). When two deuterium atoms are in the outer H2 units, forming a
      D2 is more stable than one deuterium in each H2 unit. We also discovered that
      some unstable isotopomers can rearrange to a more stable isotopomer through two
      types of isomerization: one is that a new H3(+) core is formed with more
      deuterium atoms in it; the other is that the deuterium in the central H3(+) goes
      from the interior (the bonded position) to the exterior (the unbonded position)
      while the number of deuterium atoms in the H3(+) does not change. Three
      transition states related to the isomerization were identified, two of which have
      not been reported previously. The corresponding reaction paths were also
      determined.

PMID- 24660839
TI  - Developments in interprofessional education and collaborative practice: new
      opportunities and challenges for FDI and the dental profession.

PMID- 24660840
TI  - Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in
      treatment-naive HIV-1-infected patients with HIV-1 RNA <=100,000 copies/mL: week
      96 pooled ECHO/THRIVE subanalysis.
AB  - The once daily, single-tablet regimen (STR) combining rilpivirine (RPV),
      emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) provides a
      simplified treatment option for antiretroviral therapy (ART)-naive patients with
      baseline HIV-1 RNA (BLVL) of <=100,000 copies/mL. The aim of this analysis is to
      compare long-term efficacy, safety, and tolerability of RPV+FTC/TDF vs. efavirenz
      (EFV)+FTC/TDF as individual components in subjects with BLVL <=100,000 copies/mL.
      Week 96 efficacy and safety data from subjects with BLVL <=100,000 copies/mL, who
      received daily RPV 25 mg or EFV 600 mg with FTC/TDF in the phase 3, randomized,
      double-blind, double-dummy, active-controlled, registrational trials ECHO and
      THRIVE, were analyzed. Virologic response was evaluated by intent-to-treat, time
      to loss of virological response (ITT-TLOVR), and Snapshot algorithms. Through
      Week 96, RPV+FTC/TDF demonstrated non-inferior efficacy to EFV+FTC/TDF (84% vs.
      81%, respectively; ITT-TLOVR) in 543 subjects with BLVL <=100,000 copies/mL, and
      overall rates of virologic failure (VF) were 5.9% vs. 2.4%, respectively.
      Resistance development was lower in Year 2 than Year 1. Subjects in both arms
      with suboptimal adherence (<=95%) had lower virologic responses (63% vs. 62%,
      respectively). Treatment with RPV+FTC/TDF was associated with significantly fewer
      treatment-related adverse events (AEs), grade 2-4 AEs, neurological and
      psychiatric AEs (including dizziness and abnormal dreams/nightmares), and rash.
      Additionally, grade 2-4 treatment-emergent laboratory abnormalities and grade 1-3
      lipid abnormalities were significantly less common with RPV+FTC/TDF than
      EFV+FTC/TDF. RPV+FTC/TDF demonstrated non-inferior efficacy to EFV+FTC/TDF in ART
      naive subjects with BLVL <=100,000 copies/mL and was associated with a higher
      rate of VF but a more favorable safety and tolerability profile through Week 96.

PMID- 24660841
TI  - Evaluation of beta-D-glucan biopolymer as a novel mycotoxin binder for fumonisin
      and deoxynivalenol in soybean feed.
AB  - The walls of yeast cells, which contain beta-D-glucan biopolymers, have an active
      role in reducing mycotoxins in animal feed. This study aimed to evaluate the beta
      D-glucan biopolymers as a mycotoxin binder for fumonisin (FUM) and deoxynivalenol
      (DON) toxins as well as their effect on the nutritional value of soybean, which
      is considered one of the important feed row materials. The evaluation was carried
      out using some toxigenic Fusarium isolates (Fusarium solani, F. oxysporum, and F.
      verticillioides) in vitro and in vivo. The FUM and DON levels were determined by
      immune affinity column. The F. verticillioides was the most toxigenic, followed
      by F. oxysporum and lastly F. solani, while secretion of DON toxin was determined
      to be greater than FUM with all the tested fungi. The effectiveness of beta-D
      glucan biopolymers on FUM and DON absorption was greater than clay and calcium
      propionate. In vivo, treating soybean seeds with beta-D-glucan biopolymers led to
      reduction in the level of FUM and DON toxins in seeds artificially inoculated by
      F. verticillioides. beta-D-glucan treatment also has a low effect on nutritional
      components of the seeds compared to untreated ones. In conclusion, this study
      found a new approach to reduce Fusarium mycotoxins in feed to an allowable safe
      limit and at the same time maintaining the nutritional value of these materials.

PMID- 24660842
TI  - The fate of atmospherically derived Pb in Central European catchments: insights
      from spatial and temporal pollution gradients and Pb isotope ratios.
AB  - Soils in polluted regions are generally regarded as a delayed, long-lasting
      source for Pb contamination of aquatic systems. Lead deposited on topsoil is
      slowly transported downward with particulate and colloidal organic matter, driven
      by infiltrating precipitation. Then, Pb is tightly retained in mineral soil. Lead
      export from catchments is extremely low and decoupled from the atmospheric input.
      We tested this hypothesis in 11 small catchments, differing in pollution levels.
      Input/ouput Pb fluxes were monitored for 14-15 years in an era of decreasing
      industrial Pb emission rates. Between 1996/1997 and 2010, Pb deposition fluxes
      decreased significantly, on average by 80%. At the beginning of the monitoring,
      Pb export constituted 2 to 58% of Pb input. At the end of the monitoring, Pb
      export constituted 2 to 95% of Pb input. Highly polluted sites in the northeast
      exported significantly more Pb than less polluted sites further south. The
      (206)Pb/(207)Pb isotope ratios of runoff (1.16) were identical to those of
      topsoil and present-day deposition, and different from mineral soil and bedrock.
      Lead isotope systematics and between-site flux comparisons indicated that a
      portion of the incoming Pb had a relatively short residence time in the
      catchments, on the order of decades. 

PMID- 24660843
TI  - The use of erythropoietin-stimulating agents versus supportive care in newborns
      with hereditary spherocytosis: a single centre's experience.
AB  - Hereditary Spherocytosis (HS) is a common haemolytic anaemia in which 75% of
      cases are autosomal dominant. As most newborns with HS have a family history of
      disease, haematologists often see these infants before their physiologic
      haemoglobin nadir, which is exaggerated in comparison with healthy infants. The
      objective of this study was to evaluate the frequency of implementation and cost
      of erythropoietin-stimulating agents (EPO) versus transfusion in infants with HS
      at a single paediatric programme. In the last decade, only 15% of infants with HS
      at our centre have been treated with EPO, which costs twice that of a single
      transfusion and EPO treated infants did not always avoid transfusion. Infrequent
      prescription of EPO therapy to infants with HS at our centre may be related to
      the incomplete data supporting its use.

PMID- 24660844
TI  - New hospital telemedicine services: potential market for a nighttime
      telehospitalist service.
AB  - BACKGROUND: A critical shortage in the supply of physicians in the United States
      has necessitated innovative approaches to physician service delivery.
      Telemedicine is a viable service delivery model for a variety of physician and
      health services. Telemedicine is most effective when applied where physician
      resources are scarce, patient care is time sensitive, and service volume may be
      distributed across a network. Shortages in critical care and neurology
      specialists have led to the use of tele-intensive care unit and telestroke
      services in hospital settings. These hospital-based telemedicine services have
      gained acceptance and recommendation. Hospitalist staffing shortages may provide
      an opportunity to apply similar telemedicine models to hospitalist medicine. This
      study assesses the potential market for a nighttime telehospitalist service.
      MATERIALS AND METHODS: An analysis of the Florida state hospital discharge
      dataset investigated the potential market for a new nighttime telehospitalist
      service. Admissions were filtered and stratified for common hospitalist metrics,
      time of day, and age of patients. Admissions were further expressed by hour of
      day and location. RESULTS: Nineteen percent of common hospitalist admissions
      occurred between 7:00 p.m. and 7:00 a.m., with a range of 17%-27% or 0.23-10.09
      admissions per night per facility. Eighty percent of admissions occurred prior to
      midnight. Nonrural facilities averaged 6.69 hospitalist admissions per night,
      whereas rural facilities averaged 1.35 admissions per night. CONCLUSIONS: The low
      volume of nighttime admissions indicates an opportunity to leverage a
      telehospitalist physician service to deliver inpatient medical admission services
      across a network. Lower volumes of nighttime admissions in rural facilities may
      indicate a market for telehospitalist solutions to address the dilemma of
      hospitalist staffing shortages.

PMID- 24660845
TI  - Stable closure of the cytoplasmic half-channel is required for efficient proton
      transport at physiological membrane potentials in the bacteriorhodopsin catalytic
      cycle.
AB  - The bacteriorhodopsin (BR) Asp96Gly/Phe171Cys/Phe219Leu triple mutant has been
      shown to translocate protons 66% as efficiently as the wild-type protein. Light
      dependent ATP synthesis in haloarchaeal cells expressing the triple mutant is 85%
      that of the wild-type BR expressing cells. Therefore, the functional activity of
      BR seems to be largely preserved in the triple mutant despite the observations
      that its ground-state structure resembles that of the wild-type M state (i.e.,
      the so-called cytoplasmically open state) and that the mutant shows no
      significant structural changes during its photocycle, in sharp contrast to what
      occurs in the wild-type protein in which a large structural opening and closing
      occurs on the cytoplasmic side. To resolve the contradiction between the apparent
      functional robustness of the triple mutant and the presumed importance of the
      opening and closing that occurs in the wild-type protein, we conducted additional
      experiments to compare the behavior of wild-type and mutant proteins under
      different operational loads. Specifically, we characterized the ability of the
      two proteins to generate light-driven proton currents against a range of membrane
      potentials. The wild-type protein showed maximal conductance between -150 and -50
      mV, whereas the mutant showed maximal conductance at membrane potentials >+50 mV.
      Molecular dynamics (MD) simulations of the triple mutant were also conducted to
      characterize structural changes in the protein and in solvent accessibility that
      might help to functionally contextualize the current-voltage data. These
      simulations revealed that the cytoplasmic half-channel of the triple mutant is
      constitutively open and dynamically exchanges water with the bulk. Collectively,
      the data and simulations help to explain why this mutant BR does not mediate
      photosynthetic growth of haloarchaeal cells, and they suggest that the structural
      closing observed in the wild-type protein likely plays a key role in minimizing
      substrate back flow in the face of electrochemical driving forces present at
      physiological membrane potentials. 

PMID- 24660846
TI  - On the origin of C60 fullerene solubility in aqueous solution.
AB  - In this work, we report that the surface hydroxylation of C60 molecules is the
      most likely mechanism for pristine C60 fullerenes/C60 fullerene aggregate
      stabilization in water, being independent of the method of C60 fullerene aqueous
      solution preparation. 

PMID- 24660847
TI  - Prevalence and effects of caregiving on children.
AB  - AIM: This paper reports the prevalence and its related sociodemographic factors
      of informal caregiving by underage children in Austria. The quantity and
      intensity of caregiving activities, the motivation for and effects of caregiving
      and how this differs from non-caregiving children were investigated. BACKGROUND:
      Young carers are a worldwide phenomenon. Due to methodological and sampling
      problems, little quantitative data are available. DESIGN: Cross-sectional,
      descriptive study. METHODS: Based on a random selection of 85 schools and 474
      classes, a total of 7403 children aged 10-14 years completed a self-reporting
      questionnaire that asked for children's help in their families. Descriptive and
      inferential statistics were used to analyse the data. RESULTS: In the sample,
      4.5% caregiving children were identified. The average age of young carers was
      12.5 years. Most young carers were female (69.8% vs. 52.7% in the non-young
      carers group). Young carers assumed more responsibilities (household tasks,
      general care and sibling care) than their peers. They showed a higher level of
      physical (e.g. headache 38.2% vs. 24.4%) and mental (e.g. to worry about 68.1%
      vs. 41.8%) adverse effects than non-young carers. Extrapolation suggests a rate
      of 3.5% young carers in underage children of 5-18 years in Austria. CONCLUSION:
      Data on national level are essential preconditions to initiate support for young
      carers. Nurses can promote children's health and well-being through prevention of
      an inappropriate caregiving role.

PMID- 24660848
TI  - Changes in intestinal permeability and nutritional status after cytotoxic therapy
      in patients with cancer.
AB  - Damage to intestinal mucosa may impair nutritional status and increase the demand
      for nutrients involved in intestinal cell proliferation (retinol and folate). It
      is still unclear if cytotoxic therapy affects serum concentrations of these
      nutrients in patients with cancer and if this would be associated with
      disturbances of intestinal mucosa. Intestinal permeability, serum folate, and
      retinol and nutritional status of 22 patients with hematologic malignancies and
      17 healthy volunteers [control group (CG)] were assessed before (T0) and after
      cytotoxic therapy (T1). Ingestion of lactulose and mannitol was used to assess
      intestinal permeability. Anthropometric, body composition, phase angle (PA), and
      biochemical analysis (albumin, retinol, and folate) were also performed.
      Lactulose/mannitol ratio (0.026 +/- 0.014 vs. 0.052 +/- 0.037) and lactulose
      excretion (0.27 +/- 0.18% vs. 0.53 +/- 0.6%) increased at T1. PA decreased (7.2
      +/- 1.9 degrees  vs. 6.2 +/- 0.9 degrees ). Serum folate and albumin (20.7 +/-
      9.5 nmol/L, 37.7 +/- 5.5 g/L) were lower than CG (39.2 +/- 16.4 nmol/L, 42.9 +/-
      5.2 g/L) but did not change at T1 (17.5 +/- 7.0 nmol/L, 35.9 +/- 4.5 g/L). Serum
      retinol did not differ from CG and did not change at T1 (1.83 +/- 0.30 MUmol/L
      vs. 1.69 +/- 0.3 MUmol/L; CG: 1.86 +/- 0.20 MUmol/L). Abnormal intestinal
      permeability, low serum folate levels, and its possible relationship with
      intestinal alterations, and reduced PA, may be associated with poor nutritional
      status in cancer patients. 

PMID- 24660849
TI  - Epstein-Barr virus reactivation and hemophagocytic lymphohistiocytosis in a
      patient with chronic lymphocytic leukemia.

PMID- 24660850
TI  - The impact of long-term lenalidomide exposure on the cellular composition of bone
      marrow.

PMID- 24660851
TI  - Disruption of chromosomal locus 1p36 differentially modulates TAp73 and DeltaNp73
      expression in follicular lymphoma.
AB  - The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted
      or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we
      analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic DeltaNp73
      isoforms in cases of FL with normal or abnormal 1p36. We observed a significant
      increase in DeltaNp73 expression and DeltaNp73:TAp73 ratio, lower expression of
      cleaved caspase-3 and a higher frequency of Ki-67 and proliferating cell nuclear
      antigen (PCNA) positive cells in cases of FL with abnormal 1p36. A negative
      correlation between the DeltaNp73:TAp73 ratio and cleaved caspase-3 expression,
      and a positive correlation between DeltaNp73 expression and Ki-67 or PCNA, were
      observed. The expression of TAp73 and its pro-apoptotic transcriptional targets
      BIM. PUMA and NOXA were significantly lower in FL compared to reactive follicular
      hyperplasia. Together, our data demonstrate that 1p36 disruption is associated
      with increased DeltaNp73 expression, decreased apoptosis and increased
      proliferation in FL.

PMID- 24660853
TI  - A two-coordinate manganese(0) complex with an unsupported Mn-Mg bond: allowing
      access to low coordinate homo- and heterobimetallic compounds.
AB  - This study details the synthesis and characterization of an unprecedented two
      coordinate, high-spin manganese(0) complex that incorporates an unsupported Mn-Mg
      bond, viz. L(?)MnMg((Mes)Nacnac) (L(?) = -N(Ar(?))(SiPr(i)3), Ar(?) =
      C6H2{C(H)Ph2}2Pr(i)-2,6,4; (Mes)Nacnac = [(MesNCMe)2CH](-); Mes = mesityl). This
      compound has been utilized as an "inorganic Grignard reagent" in the preparation
      of the first two-coordinate manganese(I) dimer, L(?)MnMnL* (L* = -N(Ar*)(SiMe3),
      Ar* = C6H2{C(H)Ph2}2Me-2,6,4), and the related mixed valence, bis(amido)
      hetereobimetallic complex, Mn(II)(MU-L(?))(MU-L*)Cr(0). It is also shown to act
      as a two-electron reducing agent in reactions with unsaturated substrates. 

PMID- 24660852
TI  - Characterization of gammadeltaT cells in naive and HIV-infected chimpanzees and
      their responses to T-cell activators in vitro.
AB  - BACKGROUND: gammadeltaT cells are effector cells that eliminate cancer and virus
      infected cells. Chimpanzees are an endangered species that can naturally and
      experimentally be infected with SIV and HIV, respectively, but no information
      about the functionality of gammadeltaT cells during chronic lentiviral infection
      is currently available. METHODS: Healthy and HIV-infected chimpanzee gammadeltaT
      cells were characterized by flow cytometry. gammadeltaT subsets were studied
      after stimulation with T-cell activators, and the release of cytokines was
      analyzed by Luminex assay. RESULTS: gammadeltaT-cell subsets, Vdelta1 and
      Vdelta2Vgamma9, showed different patterns in the expression of CD4, CD195,
      CD159a, and CD159c. Stimulation of gammadeltaT cells resulted in increased levels
      of CD4 and HLA-DR, which is more pronounced in Vdelta1 T cells. Distinct cytokine
      patterns were found between healthy and HIV-infected chimpanzees. CONCLUSIONS:
      Analyses of major chimpanzee gammadeltaT subsets show similarities to human
      gammadeltaT cells and suggest different functionality and roles in their immune
      response against HIV infection.

PMID- 24660854
TI  - Korean versions of the Perceived Stress Scale (PSS-14, 10 and 4): psychometric
      evaluation in patients with chronic disease.
AB  - BACKGROUND: The Perceived Stress Scale (PSS) is a representative instrument used
      to measure stress. The original PSS comprises 14 items (PSS-14) in two subscales,
      but 10- and 4-item versions are also available (PSS-10 and 4, respectively). The
      target populations of psychometric studies using the PSS have far mainly
      comprised college students, and the underlying constructs of the PSS versions are
      controversial: one factor vs. two factors and first order vs. second order.
      OBJECTIVE: The aim of this study was to evaluate the psychometric properties of
      the Korean versions of the PSS-14, 10 and 4 (designated KPSS-14, 10 and -4,
      respectively) in patients with chronic disease. METHODS: The PSS-14, 10 and 4
      were translated into Korean using forward and backward translation. Factorial
      construct validity was tested using both exploratory and confirmatory factor
      analyses. Item convergent validity and item discriminant validity were tested.
      Concurrent validity was examined using the Center for Epidemiologic Studies
      Depression scale. Known-groups validity was analysed using t-test and effect
      size. Reliability was tested using Cronbach's alpha and the intraclass
      correlation coefficient. RESULTS: Exploratory factor analysis supported a two
      factor model for all Korean versions of the PSS, and confirmatory factor analysis
      indicated that the model fit the KPSS-10 well and the KPSS-4 only marginally. The
      testing of item convergent and discriminant validity revealed a 100% scaling
      success. As expected, all scores in the KPSS-14, 10 and 4 were moderately
      correlated with depression scores and differed significantly according to gender.
      The Cronbach's alpha for the KPSS-14 and 10 exceeded the criterion of 0.70. The
      intraclass correlation coefficient values of all three Korean versions were
      satisfied. CONCLUSIONS: The KPSS-10 exhibited a first-order, two-factor
      construct, and excellent reliability and validity were established for Korean
      patients with chronic disease. The psychometric properties of the shortest
      version, KPSS-4, were only marginally acceptable.

PMID- 24660855
TI  - From waste to functional additive: toughening epoxy resin with lignin.
AB  - A novel approach to toughen epoxy resin with lignin, a common waste material from
      the pulp and paper industry, is presented in this article. First, carboxylic acid
      functionalized alkali lignin (AL-COOH) was prepared and subsequently incorporated
      into anhydride-cured epoxy networks via a one-pot method. The results of
      mechanical tests show that covalent incorporation of rigid AL-COOH into epoxy
      networks can significantly toughen the epoxy matrix without deteriorating its
      tensile strength and modulus. The addition of 1.0 wt % AL-COOH gives increases of
      68 and 164% in the critical stress intensity factor (K(IC)) and critical strain
      energy release rate (G(IC)), respectively, relative to that of neat epoxy. This
      article opens up the possibility of utilizing low-cost and renewable lignin
      feedstocks as effective toughening agents for thermoset polymers.

PMID- 24660857
TI  - Practical total syntheses of acromelic acids A and B.
AB  - Practical total syntheses of acromelic acids A (1) and B (2), which have potent
      neuro-excitatory activity, were accomplished in 13 (36% total yield) and 17 steps
      (6.9% total yield), respectively, from 2,6-dichloropyridine (8). Regioselective
      transformation of symmetric 8 provided nitroalkenes 15 and 16. The pyrrolidine
      ring was efficiently constructed by Ni-catalyzed asymmetric conjugate addition
      followed by intramolecular reductive amination. 

PMID- 24660858
TI  - A case of right atrial appendage aneurysm in a 62-year-old man.

PMID- 24660859
TI  - Repeatability of cerebrospinal fluid constant rate infusion study.
AB  - OBJECTIVE: Infusion tests are important tools to assess cerebrospinal fluid
      (CSF)dynamics used in the preoperative selection of patients for shunt surgery,
      or to predict the scope of improvement from shunt revision. The aim of this study
      was to assess the repeatability of the key quantitative parameters describing CSF
      dynamics that are determined with infusion testing. MATERIALS AND METHODS:
      Eighteen patients in whom a constant infusion test was repeated within 102 days,
      without any intermediate surgical intervention, were studied. From each test
      baseline ICP, baseline pulse amplitude, outflow resistance, elastance coefficient
      and slope of the amplitude-pressure line were calculated and investigated with a
      regression and Bland-Altman analysis. RESULTS: Significant correlations (P <
      0.01) were found for the outflow resistance (R = 0.96), the elastance coefficient
      (R = 0.778) and the slope of the amplitude-pressure line (R = 0.876). The
      estimated 95% confidence level for outflow resistance was 3 mmHg/ml min.
      Likewise, the elastance coefficient lay within a range of 0.16/ml and the slope
      of the amplitude-pressure line within 0.25. The most inconsistent parameter found
      were baseline ICP (R = 0.272) and baseline pulse amplitude (R = 0.171).
      CONCLUSION: The results of this study imply that the parameters resulting from an
      infusion study have to be considered within a range rather than as an absolute
      value.

PMID- 24660860
TI  - Outcome after repair of concurrent upper and lower canalicular lacerations.
AB  - PURPOSE: To investigate the functional and cosmetic results after primary
      surgical repair of bicanalicular lacerations. METHODS: We identified patients
      diagnosed with bicanalicular lacerations at the Eye Clinic of Rigshospitalet,
      Copenhagen from 2000 through 2009. Patient charts were reviewed and a telephone
      interview was conducted according to a standard questionnaire, regarding tearing
      and cosmesis. Symptoms (no epiphora, epiphora only when outdoors, epiphora when
      indoors, or epiphora with discharge) were compared to the healthy eye and
      scarring was graded from 0 to 10 by the patient (none to very disturbing).
      RESULTS: Fifteen patients had bicanalicular lacerations. Canalicular silicone
      stents were used in six different ways: two monostents to the lacrimal sac (n =
      1), one monostent to the nose in the upper canaliculus (n = 2), two monostents to
      the nose (n = 2), bicanalicular stent to the nose (n = 7), bicanalicular anular
      stent (n = 2), bicanalicular stent and dacryocystorhinostomy (n = 1). The surgery
      was carried out by 6 different surgeons. Eleven patients could be followed up. In
      these, epiphora was reported after primary surgery by 7 patients, and scarring
      was graded to more than 1 in 4 patients. However, it is noteworthy that 3 of 4
      patients operated with monostents had no symptoms; the fourth patient reported
      having epiphora indoors. Furthermore, the four patients operated with monostents
      graded their scaring to be 0 (n = 3) or 1 (n = 1) only. CONCLUSION: Sequelae are
      common after bicanalicular lacerations. The use of one or two monostents to the
      nose appears to be a reasonable alternative to the traditional use of one
      bicanalicular stent.

PMID- 24660861
TI  - Quantum nuclear extension of electron nuclear dynamics on folded effective
      potential surfaces.
AB  - A perennial problem in quantum scattering calculations is accurate theoretical
      treatment of low energy collisions. We propose a method of extracting a folded,
      nonadiabatic, effective potential energy surface from electron nuclear dynamics
      (END) trajectories; we then perform nuclear wave packet dynamics on that surface
      and calculate differential cross sections for two-center, one (active) electron
      systems. 

PMID- 24660862
TI  - Isolation and molecular typing of Cronobacter spp. in commercial powdered infant
      formula and follow-up formula.
AB  - Cronobacter spp. (Enterobacter sakazakii) are important foodborne pathogens.
      Infections with this pathogen can lead to neonatal meningitis, necrotizing
      enterocolitis, and bacteremia. This study examined Cronobacter spp. contamination
      in commercial powdered infant formulas (PIFs) and follow-up formulas (FUFs) in
      China. Forty-nine of 399 samples were contaminated with Cronobacter spp. and
      10.2% of the isolates were resistant to cefotaxime; in contrast, all of the
      tested isolates were susceptible to amikacin, amoxicillin/clavulanic acid,
      cefepime, ciprofloxacin, imipenem, and meropenem. Pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST) analyses produced a
      total of 16 PFGE banding patterns and 11 sequence types (STs), including 7 novel
      STs. In summary, the rates at which Cronobacter spp. were isolated from
      commercial PIF and FUF samples in China were relatively high, and the isolated
      strains exhibited high susceptibility in vitro to most antibiotics. The PFGE
      method exhibited higher typing capability than the MLST method, and molecular
      typing results revealed that the contamination of PIF and FUF with Cronobacter
      spp. in China may be mainly due to the addition of contaminated materials. Thus,
      the development of more effective control strategies during the manufacturing
      process is needed.

PMID- 24660863
TI  - A new method to increase the adsorption of protein-bound toxins in artificial
      liver support systems.
AB  - In this work, a new method, called the preconcentration method (PCM), is proposed
      to increase the adsorption of protein-bound toxins onto adsorbents in artificial
      liver support systems. In the PCM, a concentrator is installed before the inlet
      of the adsorbent cartridge. This method is validated in an experiment using
      activated carbon to remove albumin-bound bilirubin, and the mechanism of the
      increase in adsorption is theoretically explained with breakthrough curve and
      equilibrium adsorption analyses. Our results show that when this PCM is used, the
      mass transfer rate of bilirubin from solution to activated carbon is enhanced,
      the adsorbed bilirubin amount per unit mass of activated carbon is greatly
      increased, and more albumin-bound bilirubin molecules are quickly removed from
      the albumin solution. When the concentration ratio (the ratio of the inlet flow
      rate to the outflow rate of the concentrator) is 2.59, the adsorption efficiency
      of activated carbon at 120 min is increased by approximately 36%. Only
      approximately 60 min is required for the bilirubin concentration to decrease from
      19.3 to 13.0 mg/dL; however, without the PCM, nearly 180 min is needed. In
      addition, by adjusting the concentration ratio, the adsorption of albumin-bound
      bilirubin onto activated carbon can be further increased.

PMID- 24660864
TI  - Eliciting nicotine craving with virtual smoking cues.
AB  - Craving is a strong desire to consume that emerges in every case of substance
      addiction. Previous studies have shown that eliciting craving with an exposure
      cues protocol can be a useful option for the treatment of nicotine dependence.
      Thus, the main goal of this study was to develop a virtual platform in order to
      induce craving in smokers. Fifty-five undergraduate students were randomly
      assigned to two different virtual environments: high arousal contextual cues and
      low arousal contextual cues scenarios (17 smokers with low nicotine dependency
      were excluded). An eye-tracker system was used to evaluate attention toward these
      cues. Eye fixation on smoking-related cues differed between smokers and
      nonsmokers, indicating that smokers focused more often on smoking-related cues
      than nonsmokers. Self-reports of craving are in agreement with these results and
      suggest a significant increase in craving after exposure to smoking cues. In sum,
      these data support the use of virtual environments for eliciting craving.

PMID- 24660865
TI  - Observation of water separated ion-pairs between cations and phospholipid
      headgroups.
AB  - In this work, we present evidence for ion pair formation of cations with a high
      surface charge density (Na(+) and Ca(2+)) and phosphate groups of phospholipids.
      We used femto-second infrared pump-probe and dielectric spectroscopy to probe the
      dynamics of water molecules in solutions of phosphorylethanolamine and different
      types of cations. We find that sodium and calcium cooperatively retard the
      dynamics of water in solutions of phosphorylethanolamine, implying the formation
      of solvent separated ion pairs. This ion-specific interaction is absent for
      potassium, cesium and ammonium. We compare our results to dielectric spectroscopy
      experiments, which probes the rotation of all dipolar molecules and ions in
      solution. The rotation of the dipolar phosphorylethanolamine ion shows that long
      lived ion-pairs are only formed with calcium and not with ammonium, cesium,
      potassium, and sodium. This finding implies that the association between calcium
      and the phosphate is strong with lifetimes exceeding 200 ps, while the
      interaction with sodium is relatively short-lived (~20-100 ps). 

PMID- 24660866
TI  - Silibinin attenuates MPP+-induced neurotoxicity in the substantia nigra in vivo.
AB  - Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal
      dopaminergic (DA) pathway. The cause of neuronal death in PD is largely unknown,
      but it is becoming clear that inflammation plays a significant role in the
      pathophysiology of PD. Silibinin is a major flavonoid in milk thistle which has
      an anti-inflammatory activity. We investigated whether silibinin could have
      neuroprotective effects on DA neurons in the 1-methyl-4-phenylpyridinium ion
      (MPP(+))-treated animal model of PD in vivo. To address this question, animals
      received intraperitoneal (i.p.) injections 10, 50, or 100 mg/kg of silibinin,
      starting 1 day before MPP(+) injection and continued daily until 6 days post
      lesion for tyrosine hydroxylase (TH) staining, or until 1 hour prior to the
      MPP(+) injection to examine the expression levels of inflammatory proteins.
      Finally, their brains were harvested at the indicated time points for the
      analyses. Silibinin treatment with 10 mg/kg had no significantly neuroprotective
      effects in the substantia nigra (SN). However, 50 and 100 mg/kg of silibinin
      ameliorated the MPP(+)-induced neurotoxicity in the SN in a dose-dependent
      manner, and the increased levels of inflammatory molecules such as tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and inducible nitric
      oxide synthase (iNOS) by MPP(+) treatment were attenuated by treatment with 100
      mg/kg of silibinin. These results indicate that silibinin could be a useful and
      beneficial natural product offering promise for the prevention of DA neuronal
      degeneration involved in PD.

PMID- 24660867
TI  - Catalysis of CO2 absorption in aqueous solution by inorganic oxoanions and their
      application to post combustion capture.
AB  - To reduce CO2 emission into the atmosphere, particularly from coal-fired power
      stations, post combustion capture (PCC) using amine-based solvents to chemically
      absorb CO2 has been extensively developed. From an infrastructure viewpoint, the
      faster the absorption of CO2, the smaller the absorber required. The use of
      catalysts for this process has been broadly studied. In this manuscript, a study
      of the catalytic efficiencies of inorganic oxoanions such as arsenite, arsenate,
      phosphite, phosphate, and borate is described. The kinetics of the accelerated
      CO2 absorption at 25  degrees C was investigated using stopped-flow
      spectrophotometry. The catalytic rate constants of these anions for the reaction
      of CO2 with H2O were determined to be 137.7(3), 30.3(7), 69(2), 32.7(9), and
      13.66(7) M(-1)s(-1), respectively. A new mechanism for the catalytic reaction of
      oxoanions with CO2 has also been proposed. The applicability of these catalysts
      to PCC was further studied by simulation of the absorption process under PCC
      conditions using their experimental catalytic rate constants. Arsenite and
      phosphite were confirmed to be the best catalysts for CO2 capture. However,
      considering the toxicological effect of arsenic and the oxidative instability of
      phosphite, phosphate would be the most promising inorganic catalyst for PCC
      process from the series of inorganic oxoanions studied. 

PMID- 24660868
TI  - Experts' considerations on HLA-haploidentical stem cell transplantation.
AB  - Recently, novel strategies to control graft-versus-host disease and facilitate
      engraftment have allowed an increasing number of human leukocyte antigen (HLA)
      haploidentical hematopoietic stem cell transplantation (haploHSCT) to be
      performed. A meeting was convened to review the biological rationale and the
      clinical results of various T-cell-depleted (TCD) and T-cell-replete (TCR) HLA
      haploidentical 'transplant platforms'. The objective of the meeting was to
      promote discussion and consent among leading researchers in the field on three
      main crucial issues for haploHSCT: (i) eligibility criteria, (ii) choice of the
      most suitable donor, and (iii) choice of the most appropriate transplant
      platform. The experts in attendance agreed that a patient who is eligible for an
      allogeneic transplant and lacks an HLA-identical sibling or an HLA-matched
      unrelated donor should be considered for an alternative donor transplant.
      Together with the experience of the individual center, the most important
      decision criteria in choosing an alternative donor source should be the rapidity
      of transplantation so as to avoid disease relapse/progression. The choice of the
      mismatched donor should be driven by younger age, ABO blood group compatibility,
      and Cytomegalovirus status. If a TCD transplant is planned, NK-alloreactive
      donors and/or the mother should be preferred. Prospective comparative studies are
      needed to establish the relative efficacy of different transplant platforms.
      However, expertise in stem cell manipulation and in adoptive immunotherapy is
      essential if a TCD transplant platform is chosen. 

PMID- 24660869
TI  - Selecting a patient or initiating a psychoanalytic process?
AB  - The defences provoked in the analyst by the anxieties associated with the
      difficult tasks of 'assessment' and 'selection' for psychoanalysis can result in
      a tendency to think in terms of 'hurdles to be cleared' by potential
      psychoanalytic patients, rather than 'opening the gates'. This can result in a
      diminution of the analyst's capacity to enlist and sustain a psychoanalytic
      stance. Only within a psychoanalytic frame can a meaningful psychoanalytic
      process unfold, at all stages of a potential patient's movement from their first
      contact through to, possibly, entering into an analysis. The author illustrates
      the value of this thinking by describing the work of the London Clinic of
      Psychoanalysis where there has been a shift of emphasis in psychoanalytic
      consultation towards working with individuals on their potential to initiate a
      psychoanalytic process, and away from the sole aim of 'selection of a suitable
      patient'. In this paper, the author notes that when institutional culture and
      practice supports psychoanalytic identity, this makes it more possible to
      recognize and articulate the anxieties provoked by the 'emotional storm'
      inevitable in psychoanalytic consultation, and the draw towards unhelpful
      enactment that may otherwise obscure the initiation of a psychoanalytic process
      that may or may not result in analytic treatment. Illustrative case material from
      the Clinic is presented. 

PMID- 24660870
TI  - Molecular dynamics simulations of binding modes between methylene blue and DNA
      with alternating GC and AT sequences.
AB  - The understanding of interactions between small molecules and DNA is crucial to
      design new anticancer drugs targeted to DNA. Methylene blue (MB) is a
      phenothiazinium dye that has shown promising results in photodynamic therapy
      treatment. The noncovalent binding of methylene blue to DNA was experimentally
      and theoretically analyzed in the past, but certain features of the binding mode
      are still not clear. In this work, force field molecular dynamics simulations
      were performed to simulate the binding of methylene blue to alternating GC and AT
      sequences at two different ionic strengths. External, intercalative, minor
      groove, and major groove binding modes are discussed based on energetic and
      structural analyses. External and major groove complexes were found to be
      unstable structures, although for poly(dA-dT) the major groove binding mode
      cannot be discarded, especially at high ionic strengths. Minor groove and
      intercalative binding leads to stable adducts. The most energetically favorable
      orientation of the dye inside the minor groove is different for the two DNA
      sequences because of the different balances between the DNA deformation energy
      and the dye/DNA interaction energy. The intercalative binding is the most
      important interaction mode. The dye undergoes rotational transitions inside the
      intercalative pocket for both DNA sequences giving rise to three dye/DNA adducts
      that have different energetic and structural features. This rotational motion
      explains the different behavior found in experiments for the GC and AT nucleic
      acids at different ionic strengths. 

PMID- 24660871
TI  - The upper tract-transitional-cell carcinoma global study: a prospective
      observational study exploring indications, treatment modalities, and outcomes
      worldwide.

PMID- 24660872
TI  - Electrostatically controlled swelling and adsorption of polyelectrolyte brush
      grafted nanoparticles to the solid/liquid interface.
AB  - Adsorption of 20 nm diameter silica nanoparticles grafted with a high density
      brush of the weak polymeric base poly(2-(dimethylamino)ethyl methacrylate) (SiO2
      g-PDMAEMA) to the silica/aqueous interface was investigated using ellipsometry
      and streaming potential measurements. We measured SiO2-g-PDMAEMA adsorption to
      negatively charged silica surfaces in 1-100 mM sodium chloride solutions in the
      pH range 5-10 to investigate the role of electrostatics in the adsorption
      mechanism. In this system pH and ionic strength determine not only the charge
      density of the silica adsorption substrate but also the degree of ionization and
      swelling of the PDMAEMA brushes on the nanoparticles, resulting in nonmonotonic
      dependences of the extent of adsorption on pH and ionic strength. SiO2-g-PDMAEMA
      displays significantly different adsorption behavior from the linear PDMAEMA
      analogue, most notably in terms of a strongly hysteretic adsorption response to
      altered pH and a greater tendency to adsorb under weak surface attraction
      conditions that prevail at high pH. 

PMID- 24660873
TI  - Right for knowledge - the perspective of significant others of Persons with
      Memory Disorders.
AB  - RATIONALE: People have a fundamental right to know about care and services within
      health care. This right is also important for persons with memory disorders
      (PwMD) and their significant others (SO) for empowering them to manage with
      difficult situations at home and in institution. AIM: This study explores the
      self-assessed level of received knowledge about care and services of the SOs of
      PwMDs and the understandability of that knowledge. METHODS: This study employed
      an exploratory and correlational survey design in multisite settings for older
      people. Data were collected in Finland in 2010-2011 from the SOs of PwMDs (N =
      304, n = 264, response rate 87%) using questionnaires, including the Knowledge of
      Care and Services for Persons with Memory Disorders; the level of knowledge and
      the understandability of the knowledge were assessed using visual analogue scale
      (VAS 0-100). Data were analysed statistically using descriptive statistics,
      independent samples t-test, one-way analysis of variance and Pearson's
      correlations coefficients. RESULTS: The self-assessed level of received knowledge
      of SOs about care and services was low (mean 47.7 +/- 25.3 out of 100), with the
      highest level seen in medication (54.5 +/- 31.1) and memory disorder as a disease
      (54.3 +/- 30.3) and the lowest level in the services provided at home for PwMDs
      (45 +/- 30.6) and generally for SOs (38.5 +/- 31.7). SOs assessed the received
      knowledge as being understandable to a moderate degree (53.7 +/- 25.5).
      CONCLUSION: More knowledge could be delivered to PwMDs to manage in their homes
      and especially to SOs to take care of PwMDs. New educational solutions could be
      created aimed at improving the understandability of the knowledge.

PMID- 24660874
TI  - Assessing the quality and effectiveness of an updated preventive home visit
      programme for ambulatory frail older Japanese people: research protocol for a
      randomized controlled trial.
AB  - AIM: To describe the programme and research protocol of our updated preventive
      home visit programme for ambulatory frail older adults in the Japanese Long-Term
      Care Insurance system. BACKGROUND: Our previous trials have shown that the nature
      of recommendations during preventive home visits is a key issue. The present
      programme has updated our previous one by including a unique structured
      assessment with treatment recommendations tied to an ongoing programme for
      quality assurance. DESIGN: A randomized, controlled trial. METHODS: Eligible
      participants (n = 360) will be randomly assigned to home visit (n = 179) and
      control (n = 181) groups in three suburban municipalities. Nurses provide
      recommendations based on structured assessments to participants in visit group
      every 3 months from September 2011-October 2013. The primary outcomes are
      parameters related to quality of life, including activities of daily living,
      instrumental activities of daily living, depression, cognitive capacity, daily
      life satisfaction and self-efficacy for health promotion; these are collected by
      mail at baseline, 12 and 24 months. The secondary outcome is long-term care use
      over the study period. To evaluate the visit process, we are qualitatively
      analysing documentation data from the assessment sheet and chart. CONCLUSION:
      This study is collecting and analysing evidence regarding the process and
      outcomes of preventive home visits based on structured care-need assessments.
      TRIAL REGISTRATION: The study protocol was registered for the UMIN clinical
      registry approved by ICMJE (No. UMIN000006463, October 04, 2011).

PMID- 24660875
TI  - Synthesis of pyrroles from terminal alkynes, N-sulfonyl azides, and alkenyl alkyl
      ethers through 1-sulfonyl-1,2,3-triazoles.
AB  - A method for synthesis of substituted pyrroles has been developed. 1-Sulfonyl
      1,2,3-triazoles generated from terminal alkynes gave alpha-imino rhodium carbene
      complexes, which when reacted with alkenyl alkyl ethers afforded substituted
      pyrroles. The method can be efficiently applied to a one-pot sequential reaction
      starting from terminal alkynes. 

PMID- 24660876
TI  - Oxidative stress: a link between cardiovascular disease and psychiatric illness?

PMID- 24660877
TI  - In situ synthesis of NiS nanowall networks on Ni foam as a TCO-free counter
      electrode for dye-sensitized solar cells.
AB  - Nickel sulfide (NiS) nanowall networks have been prepared by a novel one-step
      hydrothermal method on a nickel (Ni) foam substrate. The Ni foam has a high
      conductivity and porous structure. To our knowledge, the Ni foam is used as a
      conductive substrate for the dye-sensitized solar cell (DSSC) for the first time.
      The Ni foam is used as not only the conductive substrate but also the Ni sources
      of the reaction. The Ni foam supported NiS prepared by this simple hydrothermal
      method shows high catalytic activity for reduction of triiodide ions. The DSSC
      with a transparent conductive oxide (TCO)-free NiS counter electrode (CE) was
      herein developed and showed a higher power conversion efficiency of 8.55% than
      that with a TCO supported NiS CE (7.47%) and a TCO supported platinum CE (7.99%).

PMID- 24660878
TI  - The relationship between online video game involvement and gaming-related
      friendships among emotionally sensitive individuals.
AB  - Some researchers believe that online gaming spaces can be socially accommodating
      environments for socially inhibited individuals, such as the socially inept,
      socially anxious, or shy. While previous research has examined, and found,
      significant links between these populations and online video game play, it
      remains unknown to what extent these spaces are contributing to tangible social
      benefits for the socially inhibited. The current study addresses this question by
      evaluating the link between gaming-related friendships and shyness, as quantified
      by emotional sensitivity. Drawing from a representative sample of German game
      players, the results indicate that emotionally sensitive players are using online
      gaming spaces differently from their less emotionally sensitive counterparts and
      reporting tangible differences in their in-game friendship networks. This
      suggests that online games hold the potential to be socially advantageous for shy
      individuals by allowing them to overcome their traditional social difficulties
      and generate new friendships as well as strengthen old ones.

PMID- 24660879
TI  - International telemedicine consultations for neurodevelopmental disabilities.
AB  - BACKGROUND: A telemedicine program was developed between the Children's National
      Medical Center (CNMC) in Washington, DC, and the Sheikh Khalifa Bin Zayed
      Foundation in the United Arab Emirates (UAE). A needs assessment and a curriculum
      of on-site training conferences were devised preparatory to an ongoing
      telemedicine consultation program for children with neurodevelopmental
      disabilities in the underserved eastern region of the UAE. MATERIALS AND METHODS:
      Weekly telemedicine consultations are provided by a multidisciplinary faculty.
      Patients are presented in the UAE with their therapists and families. Real-time
      (video over Internet protocol; average connection, 768 kilobits/s) telemedicine
      conferences are held weekly following previews of medical records. A full
      consultation report follows each telemedicine session. RESULTS: Between February
      29, 2012 and June 26, 2013, 48 weekly 1-h live interactive telemedicine
      consultations were conducted on 48 patients (28 males, 20 females; age range, 8
      months-22 years; median age, 5.4 years). The primary diagnoses were cerebral
      palsy, neurogenetic disorders, autism, neuromuscular disorders, congenital
      anomalies, global developmental delay, systemic disease, and epilepsy. Common
      comorbidities were cognitive impairment, communication disorders, and behavioral
      disorders. Specific recommendations included imaging and DNA studies, antiseizure
      management, spasticity management including botulinum toxin protocols, and
      specific therapy modalities including taping techniques, customized body vests,
      and speech/language and behavioral therapy. Improved outcomes reported were in
      clinician satisfaction, achievement of therapy goals for patients, and requests
      for ongoing sessions. CONCLUSIONS: Weekly telemedicine sessions coupled with
      triannual training conferences were successfully implemented in a clinical
      program dedicated to patients with neurodevelopmental disabilities by the Center
      for Neuroscience at CNMC and the UAE government. International consultations in
      neurodevelopmental disabilities utilizing telemedicine services offer a reliable
      and productive method for joint clinical programs.

PMID- 24660880
TI  - Synthesis of novel peptidyl adenosine antibiotic analogs.
AB  - A small library of peptidyl adenosine antibiotic analogs was synthesized, under
      the Pilot Scale Library Program of the NIH Roadmap initiative, from 2',3'-O
      isoproylideneadenosine-5'-carboxylic acid 2 in excellent yield. The coupling of
      the amino terminus of L-2-aminophenylbutyric methyl ester to a free 5'-carboxylic
      acid moiety of 2 followed by sodium hydroxide treatment led to carboxylic acid
      analog 4. Hydrolysis of this latter gave unprotected nucleoside analog 5.
      Intermediate 4 served as the precursor for the preparation of novel peptidyl
      adenosine analogs 6-18 in good yields and high purity through peptide coupling
      reactions to diverse amine derivatives. No marked anticancer and antimalaria
      activity was noted on preliminary cellular testing; however these analogs should
      be useful candidates for other types of biological activity. 

PMID- 24660881
TI  - New dinucleoside phosphonate derivatives as prodrugs of 3'-azido-3'
      deoxythymidine and beta-L-2',3'-dideoxy-3'-thiacytidine: synthesis and anti-HIV
      properties.
AB  - [Formula: see text]New phosphonate homodimers of 3'-azido-3'-deoxythymidine (AZT)
      and a phosphonate heterodimer of beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) and
      AZT were synthesized. The compounds demonstrated moderate anti-HIV activity.
      Stability of the compounds in human blood serum was studied. A correlation
      between anti-HIV activity and stability was defined. 

PMID- 24660882
TI  - Chromone-fused cytosine analogues: synthesis, biological activity, and structure
      activity relationship.
AB  - The preparation of a series of novel chromone-fused cytosine analogues, i.e.,
      chromeno[2,3-d]pyrimidines has been carried out from substituted 2-amino-4-oxo-4H
      chromene-3-carbonitriles with urea, thiourea, and guanidine under different
      reaction conditions. These chromone-fused cytosine analogues were evaluated for
      their in vitro activity against Mycobacterium tuberculosis H37Rv strain and
      different microbial pathogenic strains in cell culture for their structure
      activity relationships, respectively. Among the synthesized compounds, 2d, 3a,
      and 4e showed better results against Mycobacterium tuberculosis H37Rv. The
      compounds 2a, 2b, and 3a showed potential antibacterial activity against E. coli
      and P. aeruginosa, while the majority of compounds were found to be active
      against S. aureus as compared to ampicillin. The synthesized cytosine analogues
      having an imine (-C&dbnd;NH) have been less sensitive to the bacterial and fungal
      strains but have a more beneficial effect on Mycobacterium tuberculosis H37Rv. 

PMID- 24660883
TI  - Synthesis of novel 2'-fluoro-3'-hydroxymethyl-5'-deoxythreosyl phosphonic acid
      nucleoside analogues as antiviral agents.
AB  - A series of purine 5'-deoxyphosphonate analogues were designed and synthesized to
      mimic naturally occurring purine monophosphate from 1,3-dihydroxyacetone as
      starting material. The discovery of threosyl phosphonate nucleoside (PMDTA, EC50
      = 2.53 MUM) as a potent anti-HIV agent has led to the synthesis and biological
      evaluation of 2',3'-modified 5'-deoxyversions of the threosyl phosphonate
      nucleosides. The synthesized 2'-fluoro-3'-hydroxymethyl 5'-deoxythreosyl
      phosphonic acid nucleoside analogues 14, 18, 23, and 27 were tested for anti-HIV
      activity as well as cytotoxicity. The adenine analogue 18 exhibits weak in vitro
      anti-HIV-1 activity (EC50 = 19.2 MUM). 

PMID- 24660884
TI  - Is dry eye associated with acquired aponeurogenic blepharoptosis?
AB  - PURPOSE: To study the relation between signs of dry eye and acquired
      aponeurogenic blepharoptosis. METHODS: Prospective case-control study in which
      100 patients with uni-or bilateral acquired aponeurogenic blepharoptosis were
      matched for age and gender to 100 controls. The margin-reflex distance (MRD), the
      Schirmer-1 score, the duration of the tear film break up time (BUT), and the
      presence of any corneal staining with fluorescein were evaluated in both groups
      and compared. Data were analysed using either Fisher's exact test or linear
      regression. RESULTS: The Schirmer-1 score was <10 mm in 36 patients versus 14
      controls (p = 0.0005). It was <5 mm in 15 patients versus 5 controls (p = 0.03).
      Hard contact lenses were worn by 29 patients versus 4 controls (p = 0.000002),
      and soft contact lenses by 11 patients and 4 controls (p = 0.1). After exclusion
      of contact lens wearers from analysis, the Schirmer-1 score was <10 mm in 30 of
      the remaining 60 patients and in 17 of the remaining 92 controls (p = 0.00006).
      The tear BUT was <10 sec in 75 patients versus 71 controls (p = 0.6). Corneal
      staining was present in 25 patients versus 15 controls (p = 0.1). The score of
      the Schirmer-1 test and the MRD decreased with age in both groups. CONCLUSION:
      (1) Compared to matched controls, patients with acquired aponeurogenic
      blepharoptosis more often have a decreased aqueous tear production (as measured
      by a Schirmer-1 test). Although a low tear production may have a causative role
      in the etiology of acquired blepharoptosis, it may also be explained by a
      dampened reflex in blepharoptosis patients (2) With age, the MRD as well as the
      Schirmer-1 score decrease in both groups.

PMID- 24660886
TI  - An ERP study on initial second language vocabulary learning.
AB  - This study examined the very initial phases of orthographic and semantic
      acquisition in monolingual native English speakers learning Chinese words under
      controlled laboratory conditions. Participants engaged in 10 sessions of
      vocabulary learning, four of which were used to obtain ERPs. Performance in
      behavioral tests improved over sessions, and these data were used to define fast
      and slow learners. Most important is that ERPs in the two groups of learners
      revealed qualitatively distinct learning patterns. Only fast learners showed a
      left-lateralized increase in N170 amplitude with training. Furthermore, only fast
      learners showed an increased N400 amplitude with training, with a distinct
      anterior distribution. Slow learners, on the other hand, showed a posterior
      positive effect, with increasingly positive-going waveforms in occipital sites as
      training progressed. Possible mechanisms underlying these qualitative differences
      are discussed. 

PMID- 24660887
TI  - Neuroticism relates to daytime wakefulness and sleep devaluation via high
      neurophysiological efficiency in the bilateral prefrontal cortex: a preliminary
      study.
AB  - Higher wake promotion against sleep drive boosts cognitive processing, but it
      also seems to increase the risk of insomnia by reinforcing an obsession with
      sleep in neurotic patients. To explore whether a personality trait of neuroticism
      simultaneously facilitates wake-promoting ability and sleep devaluation via a
      common regional prefrontal function under a sleep-restricted condition, working
      memory tasks were administered to 49 healthy humans after a 2-h sleep
      restriction. Higher wake-promoting ability demonstrated in a high-load task was
      correlated with lower bilateral prefrontal activation, as measured by near
      infrared spectroscopy. Structural equation modeling revealed that neuroticism
      predicts sleep devaluation and wake-promoting ability via left and right regional
      prefrontal efficiency, respectively. Our results indicate that neuroticism
      related neural efficiency increases resilience to sleepiness, but decreases sleep
      satisfaction. 

PMID- 24660885
TI  - Diagnostic specificity and familiality of early versus late evoked potentials to
      auditory paired stimuli across the schizophrenia-bipolar psychosis spectrum.
AB  - Disrupted sensory processing is a core feature of psychotic disorders. Auditory
      paired stimuli (PS) evoke a complex neural response, but it is uncertain which
      aspects reflect shared and/or distinct liability for the most common severe
      psychoses, schizophrenia (SZ) and psychotic bipolar disorder (BDP). Evoked time
      voltage/time-frequency domain responses quantified with EEG during a typical PS
      paradigm (S1-S2) were compared among proband groups (SZ [n = 232], BDP [181]),
      their relatives (SZrel [259], BDPrel [220]), and healthy participants (H [228]).
      Early S1-evoked responses were reduced in SZ and BDP, while later/S2
      abnormalities showed SZ/SZrel and BDP/BDPrel specificity. Relatives' effects were
      absent/small despite significant familiality of the entire auditorineural
      response. This pattern suggests general and divergent biological pathways
      associated with psychosis, yet may reflect complications with conditioning solely
      on clinical phenomenology. 

PMID- 24660888
TI  - Systolic mitral valve opening and absent isovolumic relaxation: unusual
      hemodynamics of severe mitral regurgitation.

PMID- 24660889
TI  - Derivation of indices of left ventricular contractility in the setting of
      continuous-flow left ventricular assist device support.
AB  - It is important to accurately monitor residual cardiac function in patients under
      long-term continuous-flow left ventricular assist device (cfLVAD) support. Two
      new measures of left ventricular (LV) chamber contractility in the cfLVAD
      unloaded ventricle include IQ, a regression coefficient between maximum flow
      acceleration and flow pulsatility at different pump speeds; and K, a logarithmic
      relationship between volumes moved in systole and diastole. We sought to optimize
      these indices. We also propose RIQ, a ratio between maximum flow acceleration and
      flow pulsatility at baseline pump speed, as an alternative to IQ. Eleven patients
      (mean age 49 +/- 11 years) were studied. The K index was derived at baseline pump
      speed by defining systolic and diastolic onset as time points at which maximum
      and minimum volumes move through the pump. IQ across the full range of pump
      speeds was markedly different between patients. It was unreliable in three
      patients with underlying atrial fibrillation (coefficient of determination R(2)
      range: 0.38-0.74) and also when calculated without pump speed manipulation (R(2)
      range: 0.01-0.74). The K index was within physiological ranges, but poorly
      correlated to both IQ (P = 0.42) and RIQ (P = 0.92). In four patients there was
      excellent correspondence between RIQ and IQ, while four other patients showed a
      poor relationship between these indices. As RIQ does not require pump speed
      changes, it may be a more clinically appropriate measure. Further studies are
      required to determine the validity of these indices.

PMID- 24660891
TI  - Thermochemical properties and bond dissociation enthalpies of 3- to 5-member ring
      cyclic ether hydroperoxides, alcohols, and peroxy radicals: cyclic ether radical
      + (3)O(2) reaction thermochemistry.
AB  - The formation of cyclic ethers is a major product in the oxidation of
      hydrocarbons, and the oxidation of biomass derived alcohols. Cyclic ethers are
      formed in the initial reactions of alkyl radicals with dioxygen in combustion and
      precombustion processes that occur at moderate temperatures. They represent a
      significant part of the oxygenated pollutants found in the exhaust gases of
      engines. Cyclic ethers can also be formed from atmospheric reactions of olefins.
      Additionally, cyclic ethers have been linked to the formation of the secondary
      organic aerosol (SOA) in the atmosphere. In combustion and thermal oxidation
      processes these cyclic ethers will form radicals that react with (3)O2 to form
      peroxy radicals. Density functional theory and higher level ab initio
      calculations are used to calculate thermochemical properties and bond
      dissociation enthalpies of 3 to 5 member ring cyclic ethers (oxirane, yC2O,
      oxetane, yC3O, and oxolane, yC4O), corresponding hydroperoxides, alcohols,
      hydroperoxy alkyl, and alkyl radicals which are formed in these oxidation
      reaction systems. Trends in carbon-hydrogen bond dissociation energies for the
      ring and hydroperoxide group relative to ring size and to distance from the ether
      group are determined. Bond dissociation energies are calculated for use in
      understanding effects of the ether oxygen in the cyclic ethers, their stability,
      and kinetic properties. Geometries, vibration frequencies, and enthalpies of
      formation, DeltaH degrees f,298, are calculated at the B3LYP/6-31G(d,p), B3LYP/6
      31G(2d,2p), the composite CBS-QB3, and G3MP2B3 methods. Entropy and heat
      capacities, S degrees (T) and Cp degrees (T) (5 K <= T <= 5000), are determined
      using geometric parameters and frequencies from the B3LYP/6-31G(d,p)
      calculations. The strong effects of ring strain on the bond dissociation energies
      in these peroxy systems are also of fundamental interest. Oxetane and oxolane
      exhibit a significant stabilization, 10 kcal mol(-1), lower DeltafH degrees 298
      when an oxygen group is on the ether carbon relative to the isomer with the
      oxygen group on a secondary carbon. Relative to alkane systems the ether oxygen
      decreases bond dissociation energies (BDEs) on carbon sites adjacent to the ether
      by ~5 kcal mol(-1), and increases BDEs on nonether carbons ~1 kcal mol(-1). The
      cyclic structures have significant effects on the C-H, CO-OH, COO-H, and CO-H
      bond dissociation enthalpies. These values can be used to help calibrate
      calculations of larger more complex bicyclic and tricyclic hydrocarbon and ether
      species. 

PMID- 24660890
TI  - Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly
      treatment of type 2 diabetes.
AB  - In our effort to discover DPP-4 inhibitors with added benefits over currently
      commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified
      as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an
      excellent pharmacokinetic profile amenable for once-weekly human dosing and
      selected as a clinical development candidate. This manuscript summarizes the
      mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic
      properties, and human efficacy data for omarigliptin, which is currently in phase
      3 clinical development. 

PMID- 24660892
TI  - Elongated Gilman cuprates: the key to different reactivities of cyano- and
      iodocuprates.
AB  - In the past the long-standing and very controversial discussion about a special
      reactivity of cyano- versus iodocuprates concentrated on the existence of higher
      order cuprate structures. Later on numerous structural investigations proved the
      structural equivalence of iodo and cyano Gilman cuprates and their subsequential
      intermediates. For dimethylcuprates similar reactivities were also shown.
      However, the reports about higher reactivities of cyanocuprates survived
      obstinately in many synthetic working groups. In this study we present an
      alternative structural difference between cyano- and iodocuprates, which is in
      agreement with the results of both sides. The key is the potential incorporation
      of alkyl copper in iodo but not in cyano Gilman cuprates during the reaction. In
      the example of cuprates with a highly soluble substituent (R = Me3SiCH2) we show
      that in the case of iodocuprates during the reaction several copper-rich
      complexes are formed, which consume additional iodocuprate and provide lower
      reactivities. To confirm this, a variety of highly soluble copper-rich complexes
      were synthesized, and their molecular formulas, the position of the equilibriums,
      their monomers and their aggregation trends were investigated by NMR
      spectroscopic methods revealing extended iodo Gilman cuprates. In addition, the
      effect of these copper-rich complexes on the yields of cross-coupling reactions
      with an alkyl halide was tested, resulting in reduced yields for iodocuprates.
      Thus, this study gives an explanation for the thus far confusing results of both
      similar and different reactivities of cyano- and iodocuprates. In the case of
      small substituents the produced alkyl copper precipitates and similar
      reactivities are observed. However, iodocuprates with large substituents are able
      to incorporate alkyl copper units. The resulting copper-rich species have less
      polarized alkyl groups, i.e. gradually reduced reactivities. 

PMID- 24660893
TI  - Water accounting and vulnerability evaluation (WAVE): considering atmospheric
      evaporation recycling and the risk of freshwater depletion in water footprinting.
AB  - Aiming to enhance the analysis of water consumption and resulting consequences
      along the supply chain of products, the water accounting and vulnerability
      evaluation (WAVE) model is introduced. On the accounting level, atmospheric
      evaporation recycling within drainage basins is considered for the first time,
      which can reduce water consumption volumes by up to 32%. Rather than predicting
      impacts, WAVE analyzes the vulnerability of basins to freshwater depletion. Based
      on local blue water scarcity, the water depletion index (WDI) denotes the risk
      that water consumption can lead to depletion of freshwater resources. Water
      scarcity is determined by relating annual water consumption to availability in
      more than 11,000 basins. Additionally, WDI accounts for the presence of lakes and
      aquifers which have been neglected in water scarcity assessments so far. By
      setting WDI to the highest value in (semi)arid basins, absolute freshwater
      shortage is taken into account in addition to relative scarcity. This avoids
      mathematical artifacts of previous indicators which turn zero in deserts if
      consumption is zero. As illustrated in a case study of biofuels, WAVE can help to
      interpret volumetric water footprint figures and, thus, promotes a sustainable
      use of global freshwater resources.

PMID- 24660894
TI  - Stomach position versus liver-to-thoracic volume ratio in left-sided congenital
      diaphragmatic hernia.
AB  - OBJECTIVE: To describe a new grading method for stomach position (SP) in fetuses
      with left-sided congenital diaphragmatic hernia (L-CDH) using ultrasound and to
      correlate SP to liver position and to liver-to-thoracic cavity volume ratio
      (LiTR) using magnetic resonance imaging. METHODS: SP were graded at the level of
      the 4-chamber view as following: grade 1-to-4 for stomach not visualised,
      visualised anteriorly at the apex of the heart, stomach showing abdominal
      structures anteriorly and stomach with its larger part posterior to the level of
      the atrial-ventricular heart valves, respectively. The LiTR was calculated and
      correlated to SP using the Mann-Whitney U test. RESULTS: Seventy-four fetuses
      were included. Median LiTR for grade 1 SP was 0% and was not different from
      median LiTR for grade 2 SP (0%, p=NS). Median LiTR for grade 3 SP was 14.9% and
      was significantly higher than for grade 2 SP (p<0.001). Similarly, median LiTR
      for grade 4 SP was 20.7% and was significantly higher than for grade 3 SP
      (p<0.05). When SP was grade 1 or 2, liver was intra-abdominal in 21 (84%) out of
      25 fetuses while it was always intrathoracic for SP 3 or 4. CONCLUSION: In L-CDH,
      SP as described represents a simple indirect measurement of intrathoracic
      position and quantification of liver.

PMID- 24660895
TI  - Primary maternal cytomegalovirus infections during pregnancy: association of CMV
      hyperimmune globulin with gestational age at birth and birth weight.
AB  - BACKGROUND: Cytomegalovirus (CMV) hyperimmune globulin (HIG) may be helpful after
      a primary maternal CMV infection during pregnancy as a therapy for infected
      fetuses or to prevent maternal-to-fetus transmission of CMV. Although
      immunoglobulins administered during pregnancy appear safe, previous studies have
      not monitored HIG for a possible effect on duration of gestation and birth
      weight. METHODS: We used clinical data on 358 women with a primary CMV infection
      during pregnancy, 164 of whom received one or more infusions of HIG. RESULTS: The
      average birth weight of the 358 infants was 3076 g and the average gestational
      age at delivery for 351 women was 38.2 weeks. After adjusting for potential
      confounding variables, the only factor associated with low birth weight and the
      duration of gestation was the presence of symptoms at birth. The receipt of HIG
      was not associated with either a diminished birth weight or a reduced duration of
      pregnancy. The receipt of multiple doses of HIG (range 1-8) was significantly
      correlated with an increase in birth weight (p=0.006) and gestational age at
      delivery (p=0.014). This correlation was also significant for all asymptomatic
      infants and for infants whose mothers received multiple doses of HIG to prevent
      fetal infection. CONCLUSION: HIG administration during pregnancy is not
      associated with either diminished gestation or decreased birth weight and may
      enhance these parameters among women who receive multiple doses starting in early
      gestation.

PMID- 24660896
TI  - A random protein-creatinine ratio accurately predicts baseline proteinuria in
      early pregnancy.
AB  - OBJECTIVE: Data surrounding the use of a random urine protein:creatinine ratio
      (PCR) in the diagnosis of preeclampsia is conflicting. We sought to determine
      whether PCR in early pregnancy can replace the 24-hour urine collection as the
      primary screening test in patients at risk for baseline proteinuria. METHODS:
      Women requiring a baseline evaluation for proteinuria supplied a urine sample the
      morning after their 24-hour collection. The PCR was analyzed as a predictor of
      significant proteinuria (>=150 mg). A regression equation to estimate the 24-hour
      protein value from the PCR was then developed. RESULTS: Sixty of 135 subjects
      enrolled completed the study. The median 24-hour urine protein and PCR were 90 mg
      (IQR: 50-145) and 0.063 (IQR: 0.039-0.083), respectively. Fifteen patients (25%)
      had significant proteinuria. PCR was strongly correlated with the 24-hour protein
      value (r = 0.99, p < 0.001) and highly predictive of significant proteinuria (AUC
      = 0.86). A PCR cut-point of 0.079 yielded a sensitivity of 93.3% and a
      specificity of 57.8%. The resulting regression equation [total protein = 46.5 +
      904.2*PCR] accurately estimates the actual 24-hour protein (95% CI: +/-88 mg).
      CONCLUSION: A random urine PCR accurately estimates the 24-hour protein excretion
      in the first half of pregnancy and can be used as the primary screening test for
      baseline proteinuria in at-risk patients.

PMID- 24660897
TI  - Can modern biology interpret the mystery of the birth of Christ?

PMID- 24660898
TI  - Unconscious dynamics in twin pregnancy emerging from the Luscher color test.
AB  - OBJECTIVE: To investigate unconscious dynamics in women pregnant with twins,
      using Luscher's color test to objectively measure subjective color preferences,
      and compare them with women with singleton pregnancies. METHODS: The color test
      was administered to 50 Italian women with twin pregnancies and 100 women with
      singleton pregnancies. RESULTS: Both the twin and singleton pregnancy groups said
      that violet was their favorite color (50 versus 49%) and brown was their least
      favorite color (52 versus 44%), indicating that they idealized being pregnant,
      but also found it physically stressful. The twin pregnancy group chose yellow as
      their second favorite (28 versus 17%) and were most likely to combine it with
      their first choice of violet (44 versus 19%, p=0.0006), indicating that they were
      worried about their relationships with their new babies and wanted to give birth
      soon. In addition, both groups preferred form 6, the sine curve on a dark
      background, but rejected the associated brown color 6, revealing that the women
      felt the need to look after themselves. CONCLUSIONS: Both groups idealized being
      pregnant, but also found it physically stressful. However, the twin pregnancy
      group was afraid of building relationships with their babies and wanted to give
      birth soon.

PMID- 24660899
TI  - Decreased risk of prematurity after elective repeat cesarean delivery in
      Hispanics.
AB  - BACKGROUND: The current recommendation is to delay elective repeat cesarean
      deliveries (ERCD) until 39 weeks to decrease prematurity risks. Prior reports
      suggest accelerated maturity of fetuses according to race (African-Americans and
      Asians). OBJECTIVE: To analyze the effect of the Hispanic ethnicity on the
      prematurity risk after ERCD. METHODS: The US Natality Database from 2004 to 2008
      was reviewed. Inclusion criteria were singleton delivery, no trial of labor,
      repeat cesarean. Exclusion criteria were fetal anomalies, history of
      diabetes/hypertension related disorders. Outcomes analyzed were Apgar score,
      assisted ventilation, intensive care admission, surfactant/antibiotic use and
      seizures. Two groups were identified: non-Hispanic Whites (NHW) and Hispanic
      Whites (HW). Regression analysis was performed to calculate adjusted odds ratios.
      Deliveries at 36-40 weeks were studied with 40 weeks as the reference group.
      RESULTS: A total of 930421 ERCDs were identified, 396823 NHW and 236733 HW. For
      NHW, the risk of prematurity was lower at 39 weeks. For HW, there was no
      difference in the risks of prematurity at/beyond 38 weeks. CONCLUSION: There
      appears to be accelerated maturity with no increase in prematurity risk at 38
      weeks in HW delivered by ERCD. Ethnicity can be considered for patient counseling
      and decision making regarding optimal timing of elective interventions.

PMID- 24660900
TI  - Nematode Sgt1-homologue D1054.3 binds open and closed conformations of Hsp90 via
      distinct binding sites.
AB  - Heat shock protein 90 (Hsp90) is a highly conserved ATP-driven machine involved
      in client protein maturation, folding, and activation. The chaperone is supported
      by a set of cochaperones that confer client specificities. One of those proteins
      is the suppressor of G2 allele of skp1 (Sgt1), which participates together with
      Hsp90 in the immune responses of plants. Sgt1 consists of three domains: a TPR-,
      CS-, and SGS-domain, conserved in plants, yeast, and humans. The TPR-domain
      though is lacking in nematodes and insects. We observe that the Caenorhabditis
      elegans Sgt1 homologue D1054.3 binds to Hsp90 in the absence of nucleotides but
      much stronger in the presence of ATP and ATPgammaS. The latter binding mode is
      similar to p23, another CS-domain containing Hsp90 cofactor, even though binding
      is not observable for p23 in the absence of nucleotides. We use point mutations
      in Hsp90, which accumulate different conformations in the ATPase cycle, to
      differentiate between binding to open and closed Hsp90 conformations. These data
      support a strong contribution of the Hsp90 conformation to Sgt1 binding and
      highlight the ability of this cofactor to interact with all known Hsp90
      conformations albeit with different affinities. 

PMID- 24660902
TI  - A new compound from an endophytic fungus Alternaria tenuissima.
AB  - A new secondary metabolite, named altertoxin IV (1), together with altertoxin II
      (2), was isolated from the fermentation broth of Alternaria tenuissima, an
      endophytic fungal strain residing in the stem of Tribulus terrestris L. The
      structure of new compound 1 was established by HR-ESI-MS, multinuclear NMR
      spectroscopy, and single crystal X-ray diffraction method. In their in vitro
      bioassay, compound 2 exhibited moderate cytotoxic activity against PC-3 cell
      lines with an IC50 value of 14.28 MUM.

PMID- 24660903
TI  - Homogeneous perdehydrogenation and perhydrogenation of fused bicyclic N
      heterocycles catalyzed by iridium complexes bearing a functional bipyridonate
      ligand.
AB  - Homogeneous perdehydrogenation of saturated bicyclic 2,6-dimethyldecahydro-1,5
      naphthyridine and perhydrogenation of aromatic 2,6-dimethyl-1,5-naphthyridine
      with release and uptake of five molecules of H2 are efficiently achieved by
      iridium complexes bearing a functional bipyridonate ligand. Successive
      perhydrogenation and perdehydrogenation of 2,6-dimethyl-1,5-naphthryridine using
      a single iridium complex also proceed with the reversible interconversion of the
      catalytic species, depending on the presence or absence of H2. 

PMID- 24660901
TI  - Orally administered lycopene attenuates diethylnitrosamine-induced
      hepatocarcinogenesis in rats by modulating Nrf-2/HO-1 and Akt/mTOR pathways.
AB  - Hepatocarcinogenesis is one of the most prevalent and lethal cancers. We studied
      the mechanisms underlying the inhibition of diethylnitrosamine (DEN)-induced
      hepatocarcinogenesis by lycopene in rats. Hepatocarcinogenesis was induced by an
      intraperitoneal injection of DEN followed by promotion with phenobarbital for 24
      successive wk. The rats were given lycopene (20 mg/kg body weight) 3 times a week
      orally for 4 wk prior to initiation, and the treatment was continued for 24
      consecutive wk. Lycopene reduced incidence, number, size, and volume of hepatic
      nodules. Serum alanine transaminase, aspartate aminotransferase, total bilirubin,
      and malondialdehyde (MDA) considerably increased and hepatic antioxidant enzymes
      (catalase, superoxide dismutase, glutathione peroxidase) and glutathione
      decreased in DEN-treated rats when compared with the control group. Lycopene
      significantly reversed these biochemical changes and increased the expression of
      NF-E-2-related factor-2)/heme oxygenase-1, and it decreased NF
      kappaB/cyclooxygenase-2, inhibiting the inflammatory cascade and activating
      antioxidant signaling (P < 0.05). Lycopene also decreased DEN-induced increases
      in phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated p70
      ribosomal protein S6 kinase 1, phosphorylated 4E-binding protein 1, and protein
      kinase B (P < 0.05). Lycopene is an active chemopreventive agent that offers
      protection against DEN-induced hepatocarcinogenesis by inhibiting NF-kappaB and
      mTOR pathways. 

PMID- 24660904
TI  - Macromolecular crowding effect upon in vitro enzyme kinetics: mixed activation
      diffusion control of the oxidation of NADH by pyruvate catalyzed by lactate
      dehydrogenase.
AB  - Enzyme kinetics studies have been usually designed as dilute solution
      experiments, which differ substantially from in vivo conditions. However, cell
      cytosol is crowded with a high concentration of molecules having different shapes
      and sizes. The consequences of such crowding in enzymatic reactions remain
      unclear. The aim of the present study is to understand the effect of
      macromolecular crowding produced by dextran of different sizes and at diverse
      concentrations in the well-known reaction of oxidation of NADH by pyruvate
      catalyzed by L-lactate dehydrogenase (LDH). Our results indicate that the
      reaction rate is determined by both the occupied volume and the relative size of
      dextran obstacles with respect to the enzyme present in the reaction. Moreover,
      we analyzed the influence of macromolecular crowding on the Michaelis-Menten
      constants, vmax and Km. The obtained results show that only high concentrations
      and large sizes of dextran reduce both constants suggesting a mixed activation
      diffusion control of this enzymatic reaction due to the dextran crowding action.
      From our knowledge, this is the first experimental study that depicts mixed
      activation-diffusion control in an enzymatic reaction due to the effect of
      crowding.

PMID- 24660905
TI  - [6,6]-phenyl-C61-butyric acid 2-((2-(dimethylamino)ethyl)(methyl)amino)-ethyl
      ester as an acceptor and cathode interfacial material in polymer solar cells.
AB  - An amine-based, alcohol-soluble fullerene [6,6]-phenyl-C61-butyric acid 2-((2
      (dimethylamino)ethyl)(methyl)amino)-ethyl ester (PCBDAN) with 4-fold electron
      mobility of 6,6-phenyl-C61-butyric acid methyl ester (PCBM) is applied
      successfully as an acceptor and cathode interfacial material in polymer solar
      cells ITO/P3HT:PCBDAN/MoO3/Ag, where indium tin oxide (ITO) alone is used as the
      cathode and poly(3-hexylthiophene) (P3HT) is used as a donor. The X-ray
      photoelectron spectroscopy (XPS) depth profile confirming a favorable vertical
      phase separation is formed where P3HT is rich at the air/active blend interface
      and PCBDAN is rich at the buried interface with ITO and, thus, reduces the work
      function of ITO for use as the cathode. A moderate power conversion efficiency
      (PCE) of 3.1% is achieved. The slightly low PCE could be due to unoptimized
      morphology and low structure ordering of P3HT in the blends. However, this result
      demonstrates that the amine-based fullerene could be used as the acceptor and
      cathode interfacial material, which eliminated the multilayer device fabrication
      process. Because PCBDAN has high electron mobility, it would have potential
      applications in nano-structured organic solar cells. In the near future, alcohol
      processable, high-efficient organic/polymer solar cells can be anticipated. 

PMID- 24660906
TI  - Y vos, sabes quien sos? [And you, do you know who you are?].

PMID- 24660907
TI  - Complete mitochondrial genome of a wild Siberian tiger.
AB  - In this study, the complete mitochondrial genome of Siberian tiger (Panthera
      tigris altaica) was sequenced, using muscle tissue obtained from a male wild
      tiger. The total length of the mitochondrial genome is 16,996 bp. The genome
      structure of this tiger is in accordance with other Siberian tigers and it
      contains 12S rRNA gene, 16S rRNA gene, 22 tRNA genes, 13 protein-coding genes,
      and 1 control region.

PMID- 24660908
TI  - Genetic diversity of the Ethiopian Grevy's zebra (Equus grevyi) populations that
      includes a unique population of the Alledeghi Plain.
AB  - The endangered Grevy's Zebra (Equus grevyi) is confined to the Horn of Africa,
      specifically Ethiopia and Kenya. It is threatened by habitat loss and
      fragmentation due to human encroachment of historic range. Knowledge of
      population genetics is essential for the development of appropriate conservation
      actions and management. The focus of this study was to assess the heterogeneity
      and genetic distinctiveness of the two Grevy's zebra populations in Ethiopia. Non
      invasive fecal samples (N = 120) were collected during 2009-2010 from Grevy's
      zebra populations in the Alledeghi Wildlife Reserve and the Sarite area,
      Ethiopia. Analyses of a 329 bp of the mtDNA control region of 47 sequences,
      revealed the existence of two unreported haplotypes in the northern population of
      Alledeghi, that were not shared with the southern population of Sarite. The
      Sarite population is contiguous with the Grevy's zebra population in Kenya. The
      nucleotide diversity levels found in both the populations are extremely low.

PMID- 24660909
TI  - The complete mitochondrial genome of Chinese sturgeon (Acipenser sinensis).
AB  - The complete mitochondrial genome of Chinese sturgeon (Acipenser sinensis) was
      determined by direct sequencing of PCR products. The Chinese sturgeon
      mitochondrial DNA is a circular molecule (16,688 bp in length) with the typical
      gene arrangement of vertebrate mtDNA, containing 13 protein-coding genes, two
      ribosomal RNA and 22 transfer RNA genes, and a non-coding control region. Its
      control region contains 4.5 copies of unit with 82 bp long at 5' end, which has
      been reported before for this species. Phylogenetic tree based on 13 protein
      coding genes confirmed that the complete mtDNA sequence of Chinese sturgeon was
      reported here for the first time.

PMID- 24660910
TI  - The complete mitochondrial genome of Haliotis laevigata (Gastropoda: Haliotidae)
      using MiSeq and HiSeq sequencing.
AB  - The mitochondrial genome of greenlip abalone, Haliotis laevigata, is reported.
      MiSeq and HiSeq sequencing of one individual was assembled to yield a single
      16,545 bp contig. The sequence shares 92% identity to the H. rubra mitochondrial
      genome (a closely related species that hybridize with H. laevigata in the wild).
      The sequence will be useful for determining the maternal contribution to hybrid
      populations, for investigating population structure and stock-enhancement
      effectiveness.

PMID- 24660911
TI  - In silico analysis of SSRs in mitochondrial genomes of fishes.
AB  - The availability of fish mitochondrial (mt) genomes provides an opportunity to
      explore the simple sequence repeats. In the present study, mt genomes of 85 fish
      species reported from Indian subcontinent were downloaded from NCBI and
      computationally analysed for finding SSRs types, frequency of occurrence,
      mutation and evolutionary adaptation across species. A total of 92
      microsatellites in different nucleotide combinations were detected in 59 species.
      26 interspersed SSRs, mostly poly (AT)n were found in the D-loop regions in the
      species of Cyprinidae. Fifty-six SSRs of 12 bp fixed length were observed in
      eight genes only. Further, identical repeat motifs were found on the same
      location in ATP6 and ND4 genes, which were biased towards particular habitat. The
      comparison of ATP6 and ND4 gene sets to other homologous sequences showed point
      mutations. This study explores the SSRs discovery and their utility as marker for
      species and population identification.

PMID- 24660912
TI  - Complete mitochondrial genome of catfish Bagarius bagarius (Hamilton, Sisoridae;
      Siluriformes) from Indus River Sindh, Pakistan.
AB  - Complete mitochondrial genome of fresh water catfish Bagarius bagarius, was
      isolated by LA PCR (TakaRa LAtaq, Dalian, China); and sequenced by Sanger's
      method to obtain the complete mitochondrial genome, which is listed Critically
      Endangered and Red Listed species. The complete mitogenome was 16,457 bp in
      length and contains 13 typical vertebrate protein-coding genes, 2 rRNA and 22
      tRNA genes. The whole genome base composition was estimated to be 31.14% A,
      27.72% C, 15.62% G and 25.50% T. The complete mitochondrial genome of fresh water
      catfish, B. bagarius provides the basic genetic tools for breeding and
      conservation program to enhance aquaculture production.

PMID- 24660913
TI  - DNA sequence information resolves taxonomic ambiguity of the common mud crab
      species (Genus Scylla) in Indian waters.
AB  - For several years, mud crabs of genus Scylla have been misidentified owing to
      their high morphological plasticity and the absence of distinct morphological
      diagnostic characters. The taxonomic confusion of genus Scylla de Haan is
      considered to be a primary constraint to the development of aquaculture. Although
      genus Scylla was revised using morphological and genetic characteristics,
      taxonomy of Scylla species occurring in India is still not clear. In this study,
      partial sequences of two mitochondrial genes, 16S rRNA and CO1 (Cytochrome C
      oxidase subunit I) in populations of Scylla spp. obtained from eleven locations
      along the Indian coast were used to differentiate and resolve taxonomical
      ambiguity of the mud crab species in India. The sequences were compared with
      previously published sequences of Scylla spp. Both trees generated based on 16S
      rRNA and CO1 indicated that all S. tranquebarica morphotypes obtained during this
      study and S. tranquebarica sequences submitted previously from Indian waters
      reciprocally monophyletic with reference sequence of S. serrata. Both sequence
      data and morphological characters revealed that the species S. serrata (Forskal)
      is the most abundant followed by S. olivacea. Further, the 16S rRNA and COI
      haplotypes of Indian S. tranquebarica obtained in the study significantly
      differed with the known S. tranquebarica by 6.7% and 10.6% respectively whereas
      it differed with known S. serrata by 0.0-0.7% only, a difference that was not
      statistically significant. From these studies it is clear that "S. tranquebarica"
      commonly reported from India should be S. serrata (Forskal). 

PMID- 24660914
TI  - The F-type complete mitochondrial genome of Arconaia lanceolata.
AB  - In this study, complete nucleotide sequence of the F-type mitochondrial genome of
      Arconaia lanceolata (Bivalvia: Unioninae), the endemic species of freshwater
      pearl mussel in China, was first determined. The complete mitochondrial genome of
      Arconaia lanceolata is 15,782 bp in size, and encodes 35 genes, including 13
      protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs. Those genes are similar
      to most species of Unioninae in order, structure and composition. In the 13
      protein-coding genes, ND2, Cytb, ND1 and ND6 are located in the light chain while
      the rest on the heavy chain. Also, COXI, Cytb, ND1, ND6 and ND4L with ATA as
      start codon, the remaining protein-coding genes initiated with the orthodox ATG
      as start codon. There are 28 non-coding regions in the mitochondrial genome of A.
      lanceolata, the largest is of 345 bp in length, located between ND5 and tRNA(Gln)
      gene.

PMID- 24660915
TI  - The mitochondrial genome of Nobia grandis Sowerby, 1839 (Cirripedia: Sessilia):
      the first report from the coral-inhabiting barnacles family Pyrgomatidae.
AB  - This work presents the coral-inhabiting barnacle Nobia grandis Sowerby, 1839
      complete mitochondrial genome, which is the first report from the family
      Pyrgomatidae (Cirripedia: Sessilia). The N. grandis mitochondrial genome is
      15,032 bp in length, containing a total of 469 bp of non-coding nucleotides
      spreading in 11 intergenic regions (with the largest region of 376 bp). Compared
      with the pancrustacean ground pattern, there are not less than seven tRNAs
      rearranged in the N. grandis mitochondrial genome. Gene overlaps are founded in
      eight places. Nine PCGs (COX1-3, ATP6, ATP8, CYTB, ND2, ND3 and ND6) are encoded
      on the heavy strand while the remaining 4 PCGs and the two rRNAs are located on
      the light strand. As the first representative from the family Pyrgomatidae, the
      N. grandis mitochondrial genome will help us to explore the evolutionary history
      and molecular evolution of coral barnacles and Sessilia in future studies.

PMID- 24660916
TI  - The complete mitochondrial genome of the salmon shark, Lamna ditropis
      (Chondrichthyes, Lamnidae).
AB  - The complete mitochondrial genome of the salmon shark consists of 16,699 bp and
      includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, 1
      replication origin region and 1 control region. The mitochondrial gene
      arrangement of the salmon shark is the same as that of most vertebrates. Base
      composition of the genome is A (29.6%), T (28.6%), C (27.1%), and G (14.8%).

PMID- 24660917
TI  - Single nucleotide polymorphisms in the mitochondrial displacement loop region
      modifies malignant melanoma: a study in Chinese Han population.
AB  - Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop
      (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer
      risk. We investigated the malignant melanoma (MM) risk profile of D-loop SNPs in
      a case-controlled study in Chinese Han population. A statistically significant
      increase in SNP frequency for the T16362C, A16399G and T195C alleles was observed
      in MM patients (p < 0.05) comparing the MM patients to controls, which indicted
      that the patients who carry these alleles were susceptible to MM. The study
      identified SNPs in the mitochondrial D-loop could increase MM risk in Chinese Han
      people. The analysis of genetic polymorphisms in the mitochondrial D-loop can
      help identify subgroups of patients who are at a higher risk of developing MM in
      Chinese Han population, thereby helping to make therapeutic decisions for these
      patients.

PMID- 24660918
TI  - The complete mitogenome of Asiatic Short-tailed Shrew Blarinella quadraticauda
      (Soricidae).
AB  - The Asiatic Short-tailed Shrew, Blarinella quadraticauda, is an endemic shrew to
      China, and is only distributed in Sichuan. In this study, the complete
      mitochondrial genome sequence of B. quadraticauda was determined. The mitogenome
      is 17,014 base pairs in length and contains 13 protein-coding genes, 2 ribosomal
      RNA genes, 22 transfer RNA genes and 1 control region, with a base composition of
      33.3 % A, 31.8% T, 22.3% C and 12.6% G. This study contributes to illuminating
      taxonomic status of the Asiatic Short-tailed Shrew, B. quadraticauda. 

PMID- 24660919
TI  - The complete mitochondrial genome sequence of Belligobio nummifer (Cypriniformes,
      Cyprinidae).
AB  - We determined the complete mitochondrial genome (mitogenome) sequence of
      Belligobio nummifer, which is known as a cyprinid fish in mainland China, with a
      long polymerase chain reaction (PCR) method. The total length of B. nummifer
      mitogenome is 16,610 bp, consisting of 13 protein-coding genes, 22 transfer RNAs,
      2 ribosomal RNAs genes and a noncoding control region. The overall base
      composition of B. nummifer is 29.74% for A, 26.12% for T, 17.18% for G, and
      26.97% for C, with a slight AT bias of 55.86%. The complete mitogenomic data may
      provide more informative for phylogenetic approach for gudgeons phylogeny.

PMID- 24660920
TI  - Characterization of polymorphisms in the mitochondrial DNA of twelve ethnic
      groups in the Guizhou province of China.
AB  - To characterize the genetic profiles and relationships between ancient ethnic
      populations, we analyzed polymorphisms in mitochondrial DNA (mtDNA) isolated from
      the blood of 753 members of 12 ethnic groups (Buyi, Dong, Gelao, Hui, Man, Miao,
      Menggu, Mulao, Maonan, Qiang, She and Zhuang) living in the Guizhou Province of
      China. The 9-bp deletion of mtDNA was detected by the polymerase chain reaction
      (PCR) and PCR-PAGE, and 11 SNPs by restriction fragment length polymorphism and
      mini-sequencing. Thereafter, these genotyping results were verified by PCR-DNA
      sequencing. The mtDNA of these populations exhibited considerable diversity, both
      with respect to the haplogroups M and N, and subgroups thereof. The differences
      between the major ethnic groups reflected the maternal inheritance. These ethnic
      groups in Guizhou demonstrated a genetic profile that differed considerably from
      that of other Asian populations. Our findings indicate that the matrilineal
      genetic profiles of Guizhou groups are relatively complex and distinct, showing
      relationships that reflect national history and geography. 

PMID- 24660921
TI  - The complete mitochondrial genome of Phlaeoba tenebrosa (Orthoptera: Acridoidea:
      Acrididae).
AB  - The complete mitochondrial genome of Phlaeoba tenebrosa was sequenced. Its 15,648
      bp nucleotides encode 37 typical mitochondrial genes and contain 73.8% AT. All 13
      mitochondrial protein coding genes (PCGs) share the start codon ATN, except for
      cox1 (CCG start codon). The usual termination codons (TAA or TAG) and incomplete
      stop codons (T or TA) are found from 13 protein-coding genes. The most frequent
      amino acids in the PCGs are Leucine (14.02%), Serine (9.64%), Phenylalanine
      (9.13%), Isoleucine (10.44%), and the total content of these amino acids was
      43.23%. All tRNA genes could be folded into the typical cloverleaf secondary
      structure, except trnS(AGN) lacking of the dihydrouridine arm. The sizes of the
      large and small rRNA genes are 1319 bp and 841 bp, respectively. The AT content
      of the A + T-rich region is 82.6%.

PMID- 24660922
TI  - The complete mitochondrial genome sequence of the Datong yak (Bos grunniens).
AB  - Datong yak is a famous artificially cultivated breed in China. In the present
      work, we report the complete mitochondrial genome sequence of Datong yak for the
      first time. The total length of the mitogenome is 16,323 bp long, containing 13
      protein-coding genes, 22 tRNA genes, two rRNA genes and one non-coding region (D
      loop region). The gene order of Datong yak mitogenome is identical to that
      observed in most other vertebrates. The overall base composition is 33.71% A,
      25.8.0% C, 13.21% G and 27.27% T, with an A + T content of 60.98%. The complete
      mitogenome sequence information of Datong yak can provide useful data for further
      studies on molecular breeding and taxonomic status.

PMID- 24660923
TI  - The complete mitochondrial genome of the wavyband sole Pseudaesopia japonica
      (Pleuronectiformes: Soleidae).
AB  - The wavyband sole Pseudaesopia japonica is the only known member of the genus
      Pseudaesopia. In this study, we firstly determined the complete mitochondrial
      genome of P. japonica. It is 16,789 bp in length and contains two rRNA genes, 22
      tRNA genes, 13 protein-coding genes and one putative control region with the
      typical gene order and transcriptional direction in vertebrates. The overall base
      composition of mitogenome in P. japonica is 28.4% A, 30.3% C, 15.6% G and 25.7%
      T. Two start codons (ATG and GTG) and four stop codons (AGA, AGG, TAG and TAA)
      were found in 13 protein-coding genes. The 22 tRNAs range from 67 bp (tRNA-Cys
      and tRNA-Tyr) to 75 bp (tRNA-Lys) in length. The control region is 1120 bp in
      length, representing a higher proportion of A + T (65.3%) while lower of G
      (12.0%).

PMID- 24660924
TI  - The complete mitochondrial genome of the southern purple-spotted gudgeon Mogurnda
      adspersa (Perciformes: Eleotridae) through pyrosequencing.
AB  - The complete mitochondrial genome of the Critically Endangered southern purple
      spotted gudgeon, Mogurnda adspersa, was determined for the first time using 1/8
      of a 454 pyrosequencing plate. The mitogenome was assembled using the
      bioinformatic software MIRA. The M. adspersa genome organization was very similar
      to most vertebrates, being 16,523 bp in length. It contained 13 protein-coding
      genes, 22 transfer RNA, 2 ribosomal RNA genes, and 1 non-coding control region.
      The current methodology was effective to assemble the whole mitogenome using 2008
      mitochondrial reads representing 0.23% of total genomic reads produced and
      providing average mitogenome coverage of 17.4 reads per site. The whole
      mitogenome sequence provided here is deposited in NCBI with the accession number
      KJ130031 and may benefit systematics studies and conservation programs of M.
      adspersa.

PMID- 24660925
TI  - Complete mitochondrial genome of the bigeye scad Selar crumenophthalmus
      (Perciformes: Carangidae).
AB  - The bigeye scad (Selar crumenophthalmus) is a widely distributed pelagic fish
      species with highly commercial values. Little information was available about its
      genetic characteristics. In the present study, we determined the complete
      mitochondrial genome of S. crumenophthalmus by combining sequences of overlapped
      fragments amplified by PCR using primers designed for Carangidae species. The
      entire sequence was 16,610 bp in length, which included a standard set of 13
      protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 2 non-coding regions (the
      control region and the origin of light strand replication). The genome was
      composed of 27.2% A, 29.5% C, 26.5% T and 16.8% G, showing an obvious anti G bias
      commonly observed in teleosts. The complete mitogenome sequence of S.
      crumenophthalmus could contribute for the studies on phylogenetics, population
      structure and for developing fisheries management strategies.

PMID- 24660926
TI  - The complete validated mitochondrial genome of the black marlin Istiompax indica
      (Cuvier, 1832).
AB  - Two complete mitochondrial genomes of the black marlin Istiompax indica were
      assembled from approximately 3.5 and 2.5 million reads produced by Ion Torrent
      next generation sequencing. The complete genomes were 16,531 bp and 16,532 bp in
      length consisting of 2 rRNA, 13 protein-coding genes, 22tRNA and 2 coding
      regions. They demonstrated a similar A + T base (52.6%) to other teleosts.
      Intraspecific sequence variation was 99.5% for three I. indica mitogenomes and
      99.7% for X. gladius. A lower value (85%) was found for the I. platypterus
      mitogenomes from genbank and accredited to inadvertent inclusion of gene regions
      from a con-familial species in one record, highlighting the need for cautious
      downstream use of genbank data. 

PMID- 24660927
TI  - The complete mitochondrial genome of the spotted longbarbel catfish, Hemibagrus
      guttatus (Siluriformes, Bagridae).
AB  - Spotted longbarbel catfish, Hemibagrus guttatus (Siluriformes, Bagridae), is
      regarded as one of the "four famous fish" in the Pearl River system in China. So
      far, very few genomic resources from this species were available. In the present
      study, the complete mitochondrial genome of H. guttatus was determined to be
      16,528 bp long circular molecule with a typical gene arrangement of vertebrate
      mitochondrial DNA. It includes 22 transfer RNA genes, 2 ribosomal RNA genes, 13
      protein-coding genes, and a non-coding control region (D-loop). The complete
      mtDNA genome sequence obtained in this study would be useful for studying genetic
      diversity and phylogenetics in H. guttatus and related taxa in future.

PMID- 24660928
TI  - Complete mitochondrial genome sequence of northeastern sika deer (Cervus nippon
      hortulorum).
AB  - The complete mitochondrial genome of the northeastern sika deer, Cervus nippon
      hortulorum, was determined by accurate polymerase chain reaction. The entire
      genome is 16,434 bp in length and contains 13 protein-coding genes, 2 rRNA genes,
      22 tRNA genes and 1 control region, all of which are arranged in a typical
      vertebrate manner. The overall base composition of the northeastern sika deer's
      mitochondrial genome is 33.3% of A, 24.5% of C, 28.7% of T and 13.5% of G. A
      termination associated sequence and several conserved central sequence block
      domains were discovered within the control region.

PMID- 24660929
TI  - The complete mitochondrial genome of the Japanese threadfin bream, Nemipterus
      japonicus (Teleostei, Nemipteridae).
AB  - The complete mitochondrial sequence of the Japanese threadfin bream, Nemipterus
      japonicus has been determined. The circle genome is 16,995 bp in size, and
      consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control
      region. The gene order and composition of N. japonicus was similar to that of
      most other teleosts. The base composition of H-strand is 28.11% (A), 28.02% (T),
      16.64 % (G) and 27.24 % (C), with an AT content of 56.12%. All genes are encoded
      on the heavy strand with the exception of ND6 and eight tRNA genes. The
      mitochondrial genome of N. japonicus presented will be in favor of resolving
      phylogenetic relationships within the family Nemipteridae and the Perciformes.

PMID- 24660930
TI  - The first complete mitochondrial genome of Pyrrhura sp.--question about
      conspecificity in the light of hybridization between Pyrrhura molinae and
      Pyrrhura rupicola species.
AB  - The genus Pyrrhura contains at least 24 species widespread mainly through South
      America. Pyrrhura molinae (Green-cheeked Conure) and Pyrrhura rupicola (Black
      capped Conure) are treated as separate species based on morphological
      differences. Geographical ranges of these two species overlap in southern Peru.
      However, it is not clear if they occur there sympatrically or it is a
      hybridization zone. Some taxonomists conjecture their conspecific character, as
      possible hybrid individuals have been found in Puno region. We sequenced
      mitochondrial genome of specimen with phenotype typical for P. molinae. To
      confirm its species belonging, we aligned CYTB and control region (CR) sequences
      with adequate sequences of 21 Pyrrhura species. Surprisingly, analyzed P. molinae
      individual grouped together with two different individuals of P. rupicola
      species. Such incompatibility of genetic data with morphology may be only the
      result of these two species hybridization. 

PMID- 24660931
TI  - The complete mitochondrial genome of L. albella (Mantodea: Iridopterygidae).
AB  - The complete mitochondrial genome of Leptomantella albella Burmeister (Mantodea:
      Iridopterygidae) is sequenced to analyze the gene arrangement. It is a circular
      molecule of 15,534 bp in length including 37 genes typically found in other
      insects. Gene arrangement is similar to Tamolanica tamolana (Insecta: Mantodea)
      and comprises 13 protein coding genes, two rRNA genes (12S and 16S rRNA) and 22
      tRNA genes. The AT content of the overall base composition is 73.7%. The length
      of control region is 684 bp with 81.9% AT content. Protein-coding genes begin
      with ATG as start codon except ND3, ND5, ND6, ATP8 and ATP6 with ATA. COI, COII,
      ND5, ND4L and ND1 end with TAG as stop codon, while COIII, ND2, ND3, ND4, ND6,
      ATP8, ATP6 and Cyt b end with TAA.

PMID- 24660932
TI  - Complete mitogenome of the peacock sole Pardachirus pavoninus (Pleuronectiformes:
      Soleidae).
AB  - The complete mitochondrial genome of the peacock sole Pardachirus pavoninus was
      firstly determined in this study. It is 16,537 bp in length, consisting of 13
      protein-coding genes, two rRNA genes, 22 tRNA genes and one control region with
      the typical gene order in vertebrates. There are 26 bp overlaps and 28 bp short
      intergenic spaces located in 7 and 11 gene junctions, respectively. The overall
      nucleotide composition of the L-strand is 29.1% A, 29.5% C, 16.4% G and 25.0% T.
      The 22 tRNAs range from 65 bp (tRNA-Cys) to 74 bp (tRNA-Val, tRNA-Leu1, tRNA-Lys
      and tRNA-Thr) in length. Two start codons (ATG and GTG) and two stop codons (AGG
      and TAA/T) were found in 13 protein-coding genes.

PMID- 24660933
TI  - The complete mitochondrial genome sequence of the corsac fox (Vulpes corsac).
AB  - In this study, we sequenced and reported the complete mitochondrial genome of the
      corsac fox (Vulpes corsac) for the first time using blood samples obtained from a
      wild female corsac fox captured from Inner Mongolia, China. Sequence analysis
      showed it contains 12S rRNA gene, 16S rRNA gene, 22 tRNA genes, 13 protein-coding
      genes and 1 control region. 

PMID- 24660934
TI  - The complete mitochondrial genome sequence of the budgerigar, Melopsittacus
      undulatus.
AB  - Here, we describe the budgie's mitochondrial genome sequence, a resource that can
      facilitate this parrot's use as a model organism as well as for determining its
      phylogenetic relatedness to other parrots/Psittaciformes. The estimated total
      length of the sequence was 18,193 bp. In addition to the to the 13 protein and
      tRNA and rRNA coding regions, the sequence also includes a duplicated
      hypervariable region, a feature unique to only a few birds. The two hypervariable
      regions shared a sequence identity of about 86%.

PMID- 24660935
TI  - Complete mitochondrial genome of the largest living fish: whale shark Rhincodon
      typus (Orectolobiformes: Rhincodontidae).
AB  - The whale shark Rhincodon typus (Pisces: Chondrichthyes, Orectolobiformes,
      Rhincodontidae) is the largest living fish on Earth. In this study, we presented
      its complete mitogenome. It is 16,928 bp in length, contains 13 protein-coding
      genes, 2 rRNA genes, 22 tRNA genes and one control region with the typical gene
      order and transcriptional direction in the vertebrates. Overall base composition
      of the R. typus mitogenome is 33.5% A, 24.3% C, 12.8% G and 29.5% T. Two start
      codon (GTG and ATG) and two stop codon patterns (TAG and TAA/T) were found in
      protein-coding genes. The tRNA-Ser2 could not be folded into the typical
      cloverleaf secondary structure because of the replacement of its dihydrouridine
      arm by a simple loop. A termination associated sequences (TAS) and three
      conserved sequence blocks (CSB1-3) were identified in the control region.

PMID- 24660936
TI  - The complete mitochondrial genome of Saurida microlepis (Aulopiformes:
      Synodontidae).
AB  - In this study, the complete mitochondrial genome (mitogenome) sequence of Saurida
      microlepis has been determined by long PCR and primer walking methods. The
      complete mitochondrial genome is a circular molecule of 16,510 bp in length and
      contains the same set of 37 mitochondrial genes (13 protein-coding genes, 2
      ribosomal RNA (rRNA), 22 transfer RNA (tRNA)), and a control region as other bony
      fishes. Within the control region, we identified the termination-associated
      sequence domain (TAS), the central conserved sequence block domains (CSB-F, CSB
      E, CSB-D, CSB-C, CSB-B and CSB-A), and the conserved sequence block domains (CSB
      1, CSB-2 and CSB-3).

PMID- 24660937
TI  - The complete mitochondrial genome of the Asian particolored bat Vespertilio
      sinensis (Chiroptera: Vespertilionidae) in Korea.
AB  - The complete nucleotide sequence of the mitochondrial genome of the Asian
      particolored bat, Vespertilio sinensis, was determined. The genome organization,
      gene contents, and codon usage conformed to those of other bat mitochondrial
      genomes. The total length of the mitogenome of Vespertilio sinensis is 16,971 bp
      with a total base composition of 32.6% A, 29.6% T, 23.7% C and 14.0% G. The
      mitogenome consists of 13 protein-coding genes, 2 rRNA (12S and 16S RNA) genes,
      22 tRNA genes and 1 control region.

PMID- 24660938
TI  - What determines human body odour?
AB  - Human body odour and earwax type are genetically dependent on a single-nucleotide
      polymorphism (SNP) located in the ABCC11 gene. So far, it still remains to be
      clear how SNP in the ABCC11 gene is associated with human malodour. In a recent
      issue of Experimental Dermatology, Baumann et al. propose one of the underlying
      molecular pathways. Although one of the amino acid conjugated of the odorants,
      Cys-Gly-3-methyl-3-sulfanylhexanol (3M3SH), was not taken up by the transporter
      ABCC11, glutathione conjugate of 3MSH (SG-3MSH) was transported by ABCC11.
      Moreover, SG-3MSH was processed to 3M3SH by gamma-glutamyl-transferase 1 (GGT1),
      which was abundantly expressed in apocrine sweat glands. These findings may pave
      a way for the pharmacogenetics of human body odour and the development of
      innovative deodorant products. 

PMID- 24660939
TI  - Lanthanum(III) triflate catalyzed direct amidation of esters.
AB  - Lanthanum trifluoromethanesulfonate is an effective single-component catalyst for
      synthesizing a variety of amides directly from esters and amines under mild
      conditions. Highly selective amidation of esters and amines, as well as catalyst
      controlled amidation of esters, demonstrated the effectiveness of the catalyst
      system. 

PMID- 24660940
TI  - Dispersion of SWCNTs with imidazolium-rich surfactants.
AB  - Starting from previous evidence on the crucial role of imidazolium ions, long
      alkyl chains, and aromatic rings in favoring the adsorption of surfactants onto
      carbon nanotube (CNT) walls, we have synthesized novel gemini surfactants with
      the aim to optimize and identify a reference structure for CNT dispersants. The
      efficiency of the novel surfactants has been evaluated, discussed, and compared
      with already well-investigated dispersants. The good affinity of the surfactants
      for the CNT sidewalls is highlighted by the presence of resonant van Hove
      absorption and highly resolved Raman and fluorescence spectra, while the strong
      hydrophobic interactions and favorable packing between the two alkyl chains of
      the investigated gemini surfactants and the CNT sidewalls ensure good CNT
      dispersion. Our results show no selectivity toward specific
      diameters/chiralities, confirming the twin heads of imidazolium surfactants are
      pointed toward the bulk water, while the alkyl chains are arranged on the CNT
      walls, improving water solubility at the expense of potential selectivity. 

PMID- 24660941
TI  - Risk for family rejection and associated mental health outcomes among conflict
      affected adult women living in rural eastern Democratic Republic of the Congo.
AB  - Stigma due to sexual violence includes family rejection, a complex outcome
      including economic, behavioral, and physical components. We explored the
      relationship among conflict-related trauma, family rejection, and mental health
      in adult women living in rural eastern Democratic Republic of the Congo, who
      participate in a livestock-based microfinance program, Pigs for Peace. Exposure
      to multiple and different types of conflict-related trauma, including sexual
      assault, was associated with increased likelihood of family rejection, which in
      turn was associated with poorer mental health outcomes. Design of appropriate and
      effective interventions will require understanding family relationships and
      exposure to different types of trauma in postconflict environments. 

PMID- 24660942
TI  - Effective variant detection by targeted deep sequencing of DNA pools: an example
      from Parkinson's disease.
AB  - Next-generation sequencing technologies will dominate the next phase of
      discoveries in human genetics, but considerable costs may still represent a
      limitation for studies involving large sample sets. Targeted capture of genomic
      regions may be combined with deep sequencing of DNA pools to efficiently screen
      sample cohorts for disease-relevant mutations. We designed a 200 kb HaloPlex kit
      for PCR-based capture of all coding exons in 71 genes relevant to Parkinson's
      disease and other neurodegenerative disorders. DNA from 387 patients with
      Parkinson's disease was combined into 39 pools, each representing 10 individuals,
      before library preparation with barcoding and Illumina sequencing. In this study,
      we focused the analysis on six genes implicated in Mendelian Parkinson's disease,
      emphasizing quality metrics and evaluation of the method, including validation of
      variants against individual genotyping and Sanger sequencing. Our data showed 97%
      sensitivity to detect a single nonreference allele in pools, rising to 100% where
      pools achieved sequence depth above 80x for the relevant position. Pooled
      sequencing detected 18 rare nonsynonymous variants, of which 17 were validated by
      independent methods, corresponding to a specificity of 94%. We argue that this
      design represents an effective and reliable approach with possible applications
      for both complex and Mendelian genetics.

PMID- 24660944
TI  - Family advocacy for the IPS supported employment project: accomplishments and
      challenges.
AB  - TOPIC: A majority of people with serious mental illnesses want to return to work
      as part of their recovery, but access to effective employment services is
      limited. This report highlights the role that families can take to advocate for
      access to high-quality services for their relatives with mental illnesses.
      PURPOSE: This report summarizes major accomplishments of the family advocacy for
      the Individual Placement and Support (IPS) supported employment project, which is
      part of the Johnson & Johnson-Dartmouth Community Mental Health Program. SOURCES
      USED: This description draws on published literature related to the role of
      families on behalf of individuals living with serious mental health conditions
      and supported employment services. The experiences of family members as advocates
      for change are also included. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Family
      teams can play a key role in changing public policy to increase access to
      evidence-based employment services and in promoting high-quality services at the
      local level in partnership with state mental health and vocational rehabilitation
      agency leaders responsible for employment services. In addition, family teams can
      educate their peers to better understand the role of work in recovery.

PMID- 24660943
TI  - Gross, histological and ultrastructural features of the bulbourethral gland in
      the greater cane rat (Thryonomys swinderianus).
AB  - The present study examines the structure and ultrastructure of the bulbourethral
      glands in 10 sexually matured male greater cane rats raised in captivity.
      Following anaesthesia, the rats were perfusion-fixed transcardially and the
      bulbourethral glands dissected out. Upon morphologic and morphometric analysis,
      the Cowper's glands were observed to have an average volume of 0.24+/-0.08 ml, a
      diameter of 6.3+/-0.6 mm and weighs 0.199+/-0.06 g. The paired, gourd-shaped
      tubuloalveolar glands were surrounded by dense connective tissues and separated
      into lobules by capsular septae. Each lobule consists of endpiece/secretory units
      and excretory ducts lined by simple glandular epithelium and pseudo-stratified
      epithelium, respectively. The round end pieces consisted of 8-10 pyramidal to
      columnar epithelial cells with flattened, basally located nuclei and granule
      filled cytoplasm that bounded a narrow glandular lumen. The striking
      ultrastructural features of these secretory cells were the presence of some
      granules with uniform electron density and those with regions of lesser density
      as well as the absence of secretory vacuoles. Another unique characteristic of
      these secretory granules is the presence of electron dense strands radiating from
      their surfaces. The apical surfaces of the cells were also studded with abundant
      microvilli. From the findings, the structure of bulbourethral glands in the
      greater cane rat shows more resemblances to that of humans than to its rodent
      phylogeny. These findings serve as additional knowledge in the structural
      interpretation of the bulbourethral gland and its secretory products.

PMID- 24660945
TI  - Improving services for parents with psychiatric disabilities: three new
      opportunities in the field of psychiatric rehabilitation.
AB  - Despite many challenges, recent developments in the field of psychiatric
      rehabilitation offer opportunities for an increased focus on serving parents with
      psychiatric disabilities and their children. One such trend is the growth of
      psychosocial rehabilitation (PSR) programs that serve children and youth. The new
      Certificate in Children's Psychiatric Rehabilitation program offers practitioners
      education and training to meet the needs of children and families. Another
      opportunity can be found in the recent growth of family services in PSR programs
      for veterans with serious mental health problems. The Veterans Administration's
      new Psychosocial Rehabilitation and Recovery Services model explicitly includes
      family members in supporting veterans and acknowledges the need to deliver direct
      services to their spouses, children, and parents. A third relevant trend is the
      emergence of a new generation of recovery-oriented PSR services for mothers and
      fathers. Opportunities for enhanced services are provided in particular by self
      help, peer support programs for parents with lived experience.

PMID- 24660946
TI  - Brief version of the Internalized Stigma of Mental Illness (ISMI) scale:
      psychometric properties and relationship to depression, self esteem, recovery
      orientation, empowerment, and perceived devaluation and discrimination.
AB  - OBJECTIVE: The internalized stigma of mental illness impedes recovery and is
      associated with increased depression, reduced self-esteem, reduced recovery
      orientation, reduced empowerment, and increased perceived devaluation and
      discrimination. The Internalized Stigma of Mental Illness (ISMI) scale is a 29
      item self-report questionnaire developed with consumer input that includes the
      following subscales: Alienation, Discrimination Experience, Social Withdrawal,
      Stereotype Endorsement, and Stigma Resistance. Here we present a 10-item version
      of the ISMI containing the two strongest items from each subscale. METHOD:
      Participants were all outpatient veterans with serious mental illness. Following
      the rigorous scale-reduction methods set forth by Stanton and colleagues (2002),
      we selected the 10 items, tested the psychometrics of the shortened scale in the
      original validation sample (N = 127), and cross-checked the results in a second
      dataset (N = 760). RESULTS: As expected, the ISMI-10 retained the essential
      properties of the ISMI-29, including adequate internal consistency reliability
      and external validity in relation to depression, self-esteem, recovery
      orientation, perceived devaluation and discrimination, and empowerment. The ISMI
      10 scores are normally distributed and have similar descriptive statistics to the
      ISMI-29. The reliability and depression findings were replicated in a cross
      validation sample. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: We conclude that
      the ISMI-10 has strong psychometric properties and is a practical, reliable, and
      valid alternative to the original ISMI-29. Future work should test the ISMI-10 in
      more diverse samples. This shorter version should reduce respondent burden in
      program evaluation projects that seek to determine whether participation in
      psychosocial rehabilitation programming reduces internalized stigma.

PMID- 24660947
TI  - Psychiatric rehabilitation practitioner perceptions of frequency and importance
      of performance domain scales.
AB  - OBJECTIVE: The primary purpose of this article is to test if reliable performance
      domain scales can be developed for psychiatric rehabilitation practitioners
      (PRPs). METHODS: An online survey was filled out by 1,639 PRPs who provided
      demographic and frequency-based and importance-based performance domain data.
      There were 70 items each for the frequency and importance performance domains.
      Complete data for testing the research questions was available for 965 PRPs using
      frequency and 985 PRPs using importance ratings. Descriptive and correlation
      analyses tested the research question. RESULTS: The descriptive and correlation
      results supported the research question. Nine reliable performance domain scales
      were created for both frequency and importance ratings: interpersonal
      competencies, professional role, community integration, assessment/planning,
      facilitating recovery, systems competencies, diversity, supporting health and
      wellness, and transition-age youth services. CONCLUSION AND IMPLICATIONS FOR
      PRACTICE: The nine performance domain scales should be useful for future PRP job
      analyses. In addition, individual performance domain scales can be applied to
      other PRP research issues. Study limitations are acknowledged. Future research
      validating this 70-item measure is encouraged using other sources (e.g.,
      supervisor) as well as other data collection methods (e.g., interview), from
      various psychiatric rehabilitative agency settings.

PMID- 24660949
TI  - Targeting consumers in the early stages of substance use treatment: a pilot
      study.
AB  - OBJECTIVE: Engaging persons with co-occurring disorders in substance use
      treatment presents a significant challenge for public mental health service
      providers. Standardized, user-friendly guidelines may have great benefit for
      community mental health outreach staff working with individuals with co-occurring
      disorders. The purpose of this study is to describe the impact of a brief,
      structured goal development curriculum ("Fresh Start") on clinicians'
      motivational interviewing skills and to assess clinician and consumer
      satisfaction with the curriculum. METHOD: Four clinicians, each working with 3-4
      consumer participants, were assessed with the Yale Adherence and Competency Scale
      prior to and during use of Fresh Start to determine improvements in motivational
      interviewing and goal setting. Consumer participants were assessed in brief
      qualitative interviews to assess satisfaction. Chart-review of routinely
      collected substance use data was used to assess reductions in use. RESULTS:
      Clinicians demonstrated high ratings in relational motivational interviewing
      skills at baseline which were maintained at study conclusion. Clinicians had
      lower technical motivational interviewing skills at baseline and made modest
      improvements in motivational interviewing techniques targeting increasing change
      talk. Fresh Start participants completed an average of 10 sessions (SD = 2.35).
      Among the 16 consumers who volunteered to participate in using the Fresh Start
      curriculum, 12 finished the program and 9 decided to reduce use and composed a
      sobriety plan. CONCLUSIONS AND IMPLICATION FOR PRACTICE: High rates of completion
      indicate acceptability of the curriculum and feasibility for implementing the
      program in a community setting. Short, goal-setting interventions are needed and
      under proper conditions may be teachable in vivo.

PMID- 24660950
TI  - Participant experiences in peer- and clinician-facilitated mental health recovery
      groups for veterans.
AB  - OBJECTIVE: The purpose of the study was to characterize and compare participants'
      experiences of peer-facilitated versus clinician-facilitated recovery groups for
      veterans with mental illness. METHOD: We analyzed qualitative data from 24
      interviews with veterans who participated in mental health recovery groups led by
      peer or clinician facilitators. RESULTS: Subtle differences in group structure,
      participation/communication and utility/relevance between peer- and clinician
      facilitated groups were identified. Participants experienced both peer and
      clinician facilitators as helpful in promoting recovery, though they appeared to
      do this in different ways. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Peer and
      clinician facilitators offer different strengths in the promotion of mental
      health recovery.

PMID- 24660951
TI  - Predictors of loneliness of clubhouse members.
AB  - OBJECTIVE: Loneliness can impede subjective experiences of recovery. This study
      examines the relationship between clubhouse participation and loneliness using
      standardized instruments while controlling for age, gender, living status, and
      social network characteristics. METHOD: A random sample of 126 members from one
      clubhouse was recruited for this cross-sectional investigation. A hierarchical
      multiple regression analysis was performed to examine the association between
      participation and loneliness. RESULTS: A greater number of clubhouse visits,
      greater perceived availability of social support and higher levels of overall
      satisfaction with social network relationships were significantly related to a
      lower level of loneliness after controlling for covariates. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Service providers may want to pay more attention to
      those members experiencing loneliness and help them connect with others. Future
      studies using longitudinal analyses are needed to further assess the causal
      relationship between clubhouse participation and loneliness. Multiple aspects of
      participation should be examined.

PMID- 24660952
TI  - Life, liberty, and the pursuit of happiness: reframing inequities experienced by
      people with severe mental illness.
AB  - TOPIC: In the Declaration of Independence, Thomas Jefferson stated that citizens
      of the new republic had fundamental and inalienable rights to "life, liberty and
      the pursuit of happiness." PURPOSE: The purpose of this article is to reframe
      inequities experienced by people living with severe mental illnesses in terms of
      violations of Jeffersonian rights to "life, liberty and the pursuit of
      happiness." We simultaneously consider governmental and clinical efforts to
      address identified inequities and uphold these rights. SOURCES USED: The broad
      research literature on severe mental illnesses was examined. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: People with severe mental illnesses experience
      numerous inequities regarding "life, liberty and the pursuit of happiness." These
      inequities include diminished life expectancy, excessive involuntary commitment
      and elevated rates of unemployment and homelessness. Governmental and clinical
      responses to such inequities include the Affordable Care Act and the Olmstead
      Decision, as well as recovery-oriented interventions such as Supported Employment
      and Supported Housing.

PMID- 24660953
TI  - Creating a learning culture.
AB  - TOPIC: This column describes the efforts of an agency to build a learning culture
      as part of changing their approach to service delivery, when adopting a focus on
      psychiatric rehabilitation and recovery. PURPOSE: This example of one
      organization's challenges and successes in workforce development provides an
      alternative approach to the common single-session staff training that typically
      fails to change practice. SOURCES USED: This description draws from published
      material on communities of practice, technical consultation, and agency
      experience. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Training alone is not
      enough to create change. An organizational commitment to ongoing quality
      improvement, along with available and accessible technical assistance for staff,
      creates an environment where change is anticipated, managed, and celebrated.

PMID- 24660954
TI  - Radiographic observers' ability to recognize patient movement during cone beam
      CT.
AB  - OBJECTIVES: To assess radiographic observers' ability to recognize patient
      movement during cone beam CT and to decide early termination of the examination.
      METHODS: 100 patients were video-recorded during cone beam CT examination.
      Patients' videos were cropped twice: fitting the active 20-s examination time or
      the initial non-radiation 3 s of the examination. x- and y-coordinates of pre
      defined points marked on the patient's face were used to define the reference
      standard for movement in the 20-s videos. A sample of 40 non-moving and 20 moving
      patients was selected. Eight observers scored the videos. The 3-s videos were
      scored: 0, the patient did not move; 1, the patient moved and the examination
      should be terminated. The 20-s videos were scored: 0, the patient did not move;
      1, the patient moved. Re-assessment of 15% of the videos provided intra-observer
      reproducibility. The 20-s videos were compared with the reference standard
      providing sensitivity and specificity values (movement/non-movement recognition).
      The scores of the 3-s videos were compared with the scores of the 20-s videos.
      RESULTS: Intra- and interobserver reproducibility ranged from substantial to
      almost perfect for both videos. The 20-s videos allowed patient movement
      recognition with a high specificity and a medium to high sensitivity. The 3-s
      videos allowed early termination of the examination with a small number of
      incorrect positive scores. The majority of the patients scored as moving in the
      20-s videos were detected in the 3-s videos. CONCLUSIONS: By observing video
      recordings, trained observers are able to recognize patient movement during cone
      beam CT examination with high specificity and to decide an early termination of
      the examination.

PMID- 24660955
TI  - Potential energy curves and lifetimes of low-lying excited electronic states of
      CSe studied by configuration interaction method.
AB  - In this work, we performed a high level ab initio study on the low-lying
      electronic states of CSe, utilizing MRCI+Q (the internally contracted
      multireference configuration interaction, and Davidson's correction) method with
      scalar relativistic and spin-orbit coupling effects taken into account. The
      potential energy curves of 18 Lambda-S states associated with the lowest
      dissociation limit of CSe molecule, as well as those of 50 Omega states generated
      from the Lambda-S states were computed. The spectroscopic parameters of bound
      states were evaluated, which agree well with existing theoretical and
      experimental results. With the aid of calculated spin-orbit matrix elements and
      the Lambda-S compositional variation of the Omega states, the spin-orbit
      perturbations of low-lying states to the A(1)Pi and a(3)Pi states are analyzed.
      Finally, the transition dipole moments of A(1)Pi, A'(1)Sigma(+), a(3)Pi0+, and
      a(3)Pi1 to the ground X(1)Sigma(+) state as well as the lifetimes of the four
      excited states were evaluated. 

PMID- 24660956
TI  - Synergistic activity of biocides and antibiotics on resistant bacteria from
      organically produced foods.
AB  - Synergism between biocides and antibiotics was investigated in 20 biocide and
      antibiotic-resistant bacterial strains that were previously isolated from
      organically produced foods, according to their antimicrobial resistance profiles.
      Most of the antibiotic/biocide combinations yielded synergistic interactions,
      reducing the inhibitory concentrations of biocides and antibiotics by 4- to 16
      fold. Among enterococci, synergism with biocides was detected for amoxicillin
      (AM), cefuroxime (CX), erythromycin (EM), ciprofloxacin (CP), and
      trimethoprim/sulphametoxazol (T/S). Among staphylococci, interactions were
      synergistic (AM) and either synergistic or indifferent (CX and EM, depending on
      biocide). Among the three methicillin-resistant Staphylococcus aureus clinical
      strains included in the study, the combinations of methicillin and triclosan or
      hexachlorophene acted synergistically in all strains, but interactions were
      either synergistic or indifferent for the other biocides, depending on the
      strain. All combinations tested were synergistic for Lactobacillus (AM, CX, EM,
      and CP) and Micrococcus (AM, EM). In Salmonella, interactions were indifferent
      (AM, CX, EM, and CP) or synergistic (T/S). Synergism with biocides was also
      detected in Klebsiella isolates (AM, CX, and T/S), Enterobacter sp. (AM, CX, EM,
      and T/S), Pantoea (AM, CX, EM, CP, and T/S), and Chryseobacterium sp. (EM). These
      results suggest that combinations of biocides and antibiotics may open new
      possibilities to combat antimicrobial resistance. 

PMID- 24660958
TI  - Water tetrahedrons, hydrogen-bond dynamics, and the orientational mobility of
      water around hydrophobic solutes.
AB  - Despite being intensively studied, the magnitude of specific structural and
      dynamic perturbations of water next to hydrophobic surfaces remains a matter of
      debate. Here we show, from molecular dynamics, that the structure of a subset of
      water molecules in the first hydration layer, those preserving four nearest water
      neighbors, resembles that of water at ~10  degrees C, and that the origin of the
      orientational slowdown is mainly a decrease of the hydrogen-bond (HB) acceptor
      switch frequency, while water structuring plays a minor role, slightly
      accelerating HB acceptor switches. By portraying the mean HB dynamics of water as
      a doubly periodic event, we demonstrate that the orientational retardation factor
      is effectively defined by the ratio of the HB acceptor switch period in the
      hydration layer and bulk. Excluded volume delays HB acceptor switches,
      accelerating the orientational relaxation of ~1/3 of the water molecules on the
      hydration layer in this time scale, but this is largely exceeded by the decrease
      of the HB switch frequency, consistent with 2D IR spectroscopy experiments, and
      at the origin of longer HB lifetimes. The orientational mobility of water
      populations with long HB lifetimes is also probed, and although a relaxation
      plateau is observed at ~10 ps consistent with fs IR spectroscopy experiments, no
      water molecule is rotationally frozen at any time scale. The proposed molecular
      picture is consistent with fs IR, 2D IR, and NMR experimental results on the
      orientational retardation of water and reveals the magnitude of "hidden" enhanced
      ordered water pentamers formed near hydrophobic solutes. 

PMID- 24660957
TI  - Prolonged marital stress is associated with short-lived responses to positive
      stimuli.
AB  - Marital stress is associated with a higher incidence of psychiatric disorders, in
      particular major depression. One pathway through which marital stress may impact
      emotional health is by compromising emotion-responding processes. We examined a
      longitudinal sample of adults (N = 116; 59 males; 39-84 years) to verify how
      marital stress predicts reactivity to, and recovery from, emotional provocation.
      Individuals watched positive, neutral, and negative pictures while an objective
      measure of affective state, corrugator supercilii muscle activity, was recorded
      continuously. Our results indicate that marital stress is associated with short
      lived responses to positive pictures, indexed by a less persistent decrease in
      corrugator activity after picture offset. Extending beyond the prior focus on
      negative emotional processes, these results suggest that social stress may impact
      health by influencing the time course of responding to positive events. 

PMID- 24660959
TI  - Osteoradionecrosis of the exenterated orbit.
AB  - Osteoradionecrosis (ORN) occurs in an estimated 2% of head and neck-irradiated
      patients. It is seen most commonly in the mandible with other reported sites
      including the maxilla, temporal bone, clavicle, and vertebrae. It is defined as
      an area of exposed devitalised irradiated bone, with failure to heal during a
      period of at least 3 months, in the absence of local neoplastic disease. We
      report 2 cases of ORN following postoperative radiotherapy given to patients who
      had undergone an orbital exenteration. ORN can develop spontaneously in one-third
      of cases, although in the majority of patients, it is induced by secondary
      trauma. Radiotherapy induces an endarteritis in the small blood vessels of bone,
      thus favouring the generation of small thrombi that obliterate the vascular lumen
      and interrupt tissue perfusion. Likewise, irradiation impairs the function of
      osteoblasts, manifesting as osteopenia, with impairment of the repair and
      remodelling capacity of bone. Prior radiation exposure can thus decrease bone
      vascularity and injure its reserve reparative capacity. It is important to
      differentiate ORN from local recurrence of malignancy, bone metastasis, radiation
      induced sarcoma, and infection. CT and MRI are effective diagnostic tools.
      Clinical management of ORN is complex and unsatisfactory. Treatment remains
      difficult, and prevention is paramount. A history of radiotherapy should alert
      clinicians to detect bone exposure or excessively prolonged socket healing. Early
      diagnosis with a high index of suspicion can achieve higher control rates with
      conservative management. Our case series reports a rare, previously unreported,
      but important complication of radiation therapy of the exenterated orbit.

PMID- 24660960
TI  - Copper-mediated trifluoromethylthiolation of alpha-diazoesters.
AB  - A novel Cu-mediated trifluoromethylthiolation of diazo compounds has been
      developed that provides a convenient synthetic route for the efficient alpha
      trifluoromethylthiolation of simple esters under mild reaction conditions. The
      reaction is typically carried out at room temperature, and water could be used to
      promote the reaction. 

PMID- 24660961
TI  - Size dependence of shape and stiffness of single sessile oil nanodroplets as
      measured by atomic force microscopy.
AB  - This article presents results and guidelines on the quantitative analysis of
      size, shape, and stiffness of single sessile oil droplets in air and in water.
      Atomic force microscopy (AFM) facilitates the analysis of micro- and nanoscale
      droplets which are of growing importance for agrochemicals, cosmetics, or
      foodstuffs containing emulsions with nanoscale compartments or droplets.
      Measurement of droplet shape and stiffness provides information on the contact
      angle with the support surface as well as the interfacial tension of the liquid
      liquid interface. In this study, micro- and nanoscale droplets were imaged both
      in amplitude modulation (AM) and force mapping modes. The effects of the AM mode
      set point ratio on the measured droplet shape are discussed, and a modified
      spherical cap model is suggested to extract the droplet-substrate contact angle.
      This model was applied to a population of different sized oil droplets imaged in
      water and led to the finding that the contact angle with the solid support varies
      with the droplet size. Force mapping was undertaken to measure the droplet
      stiffness as a function of the droplet size. Smaller droplets were found to be
      stiffer, in reasonable agreement with the Attard-Miklavcic model [Langmuir 2001,
      17, 8217-8223] which describes the deformation of a sessile droplet in the
      nonwetting regime, i.e., by partial wrapping of the droplet around the probe
      surface. The model limitations are discussed in terms of the diverging droplet
      stiffness predicted for droplet radii similar to the probe radius as well as the
      error propagation associated with the droplet shape function. 

PMID- 24660962
TI  - Self-assembling peptide of D-amino acids boosts selectivity and antitumor
      efficacy of 10-hydroxycamptothecin.
AB  - D-peptides, which consist of D-amino acids and can resist the hydrolysis
      catalyzed by endogenous peptidases, are one of the promising candidates for
      construction of peptide materials with enhanced biostability in vivo. In this
      paper, we report on a self-assembling supramolecular nanostructure of D-amino
      acid-based peptide Nap-G(D)F(D)F(D)YGRGD (D-fiber, (D)F meant D-phenylalanine,
      (D)Y meant D-tyrosine), which were used as carriers for 10-hydroxycamptothecin
      (HCPT). Transmission electron microscopy observations demonstrated the
      filamentous morphology of the HCPT-loaded peptides (d-fiber-HCPT). The better
      selectivity and antitumor activity of D-fiber-HCPT than L-fiber-HCPT were found
      in the in vitro and in vivo antitumor studies. These results highlight that this
      model D-fiber system holds great promise as vehicles of hydrophobic drugs for
      cancer therapy.

PMID- 24660963
TI  - Cardiovascular biomarkers in patients with psoriasis.
AB  - Psoriasis is a systemic inflammatory disease of the skin with associated
      comorbidity. Severe forms of psoriasis are associated with increased mortality,
      which might be due to cardiovascular (CV) comorbidity. In this study, we
      investigated in 79 patients with psoriasis compared to 80 healthy volunteers
      different biomarkers that play a role in vascular disease and inflammation, such
      as C-reactive protein (CRP), human soluble CD40 ligand (sCD40L), oxidized low
      density lipoprotein (ox-LDL), human matrix Gla protein (MGP) and fetuin-A. Our
      results showed that CRP (P < 0.0001), sCD40L (P < 0.0001) and MGP (P < 0.0001)
      were increased in the patient cohort. Fetuin-A showed decreased serum levels in
      patients with psoriasis (P < 0.0001), whereas ox-LDL did not show any significant
      difference. In multivariate analyses controlling for sex, age and BMI, these
      findings were confirmed. Thus, CV biomarkers are altered in patients with
      psoriasis. If the decrease in fetuin-A as well as the increase in sCD40L can be
      proven in further studies, these biomarkers may help to characterize a subgroup
      of patients who are at risk to develop CVD and/or monitor the effect of
      therapeutic antipsoriatic strategies on concomitant diseases. This knowledge may
      be useful in the management of high-need patients with psoriasis. 

PMID- 24660964
TI  - An approach to the histomorphological and histochemical variations of the humerus
      cortical bone through human ontogeny.
AB  - For many years, clinical and non-clinical investigations have investigated
      cortical bone structure in an attempt to address questions related to normal bone
      development, mineralisation, pathologies and even evolutionary trends in our
      lineage (adaptations). Research in the fields of medicine, materials science,
      physical anthropology, palaeontology, and even archaeobiology has contributed
      interesting data. However, many questions remain regarding the histomorphological
      and histochemical variations in human cortical bone during different stages of
      life. In the present work, we describe a study of long bone cortex
      transformations during ontogeny. We analysed cross-sections of 15 human humeri
      histomorphologically and histochemically from perinatal to adult age, marking and
      quantifying the spatial distribution of bone tissue types using GIS software and
      analysing the mineral composition and crystallinity of the mineralised cortex
      using Raman spectroscopy and X-ray diffraction. Our results allowed us to propose
      that human cortical bone undergoes three main 'events' through ontogeny that
      critically change the proportions and structure of the cortex. In early
      development, bone is not well mineralised and proportionally presents a wide
      cortex that narrows through the end of childhood. Before reaching complete
      maturity, the bone mineral area increases, allowing the bone to nearly reach the
      adult size. The medullary cavity is reduced, and the mineral areas have a highly
      ordered crystalline structure. The last event occurs in adulthood, when the
      'oldest' individuals present a reduced mineralised area, with increasing non
      mineralised cavities (including the medullary cavity) and reduced crystalline
      organisation. 

PMID- 24660966
TI  - Anti-inflammatory diterpenoids from the roots of Euphorbia ebracteolata.
AB  - Thirteen diterpenoids (1-13), including two new norditerpene lactones (1-2) and
      eight new rosane diterpenoids (3-10), were isolated from the roots of Euphorbia
      ebracteolata. The structures were determined by 1D and 2D NMR, HRESIMS, and
      electronic circular dichroism (ECD). The ECD-based empirical rule for alpha,beta
      unsaturated-gamma-lactones was applied to determine the absolute configurations
      of 1 and 2. Compounds 7, 10, and 13 exhibited significant inhibition of nitric
      oxide production in RAW 264.7 lipopolysaccharide-induced macrophages, with IC50
      values of 2.44, 2.76, and 1.02 MUM, respectively. 

PMID- 24660965
TI  - Non-native soluble oligomers of Cu/Zn superoxide dismutase (SOD1) contain a
      conformational epitope linked to cytotoxicity in amyotrophic lateral sclerosis
      (ALS).
AB  - Soluble misfolded Cu/Zn superoxide dismutase (SOD1) is implicated in motor neuron
      death in amyotrophic lateral sclerosis (ALS); however, the relative toxicities of
      the various non-native species formed by SOD1 as it misfolds and aggregates are
      unknown. Here, we demonstrate that early stages of SOD1 aggregation involve the
      formation of soluble oligomers that contain an epitope specific to disease
      relevant misfolded SOD1; this epitope, recognized by the C4F6 antibody, has been
      proposed as a marker of toxic species. Formation of potentially toxic oligomers
      is likely to be exacerbated by an oxidizing cellular environment, as evidenced by
      increased oligomerization propensity and C4F6 reactivity when oxidative
      modification by glutathione is present at Cys-111. These findings suggest that
      soluble non-native SOD1 oligomers, rather than native-like dimers or monomers,
      share structural similarity to pathogenic misfolded species found in ALS patients
      and therefore represent potential cytotoxic agents and therapeutic targets in
      ALS. 

PMID- 24660967
TI  - Kinetics of PCDD/Fs formation from non-wood pulp bleaching with chlorine.
AB  - Chlorine bleaching is still practiced by most of nonwood pulp and paper mills,
      resulting in a considerable amount of polychlorinated dibenzo-p-dioxins and
      polychlorinated dibenzofurans (PCDD/Fs) formation and emission. In this study,
      the effects of primary chlorination conditions on the formation of PCDD/Fs from
      nonwood pulp bleaching with elemental chlorine were investigated. It was found
      that low-chlorinated PCDD/Fs were usually formed and then underwent further
      chlorination to form highly chlorinated PCDD/Fs with increasing chlorination
      time. Higher available chlorine dosages and lower system pH values greatly
      accelerated dioxin formation, and pH 3 was the threshold for the formation of
      tetra- to octa-CDD/Fs. Higher temperatures promoted the formation of lower
      chlorinated PCDD/Fs, while caused significant reduction of tetra- to hepta-CDDs
      and penta- to octa-OCDFs. PCDFs were formed much faster than PCDDs. A first-order
      kinetic model showed a good fit to the data for tetra- to oct-CDFs formation
      under different chlorination conditions, indicating that chlorine substitution
      was the rate determining step for their formation. Finally, the optimum
      chlorination conditions for minimizing and eliminating the formation of 2,3,7,8
      TCDD/TCDF in nonwood pulp bleaching with elemental chlorine were established. 

PMID- 24660968
TI  - Lithocarpus polystachyus REHD leaf aqueous extract inhibits human breast cancer
      growth in vitro and in vivo.
AB  - Lithocarpus polystachyus leaves have been used as tea beverage and folk medicine
      for healthy care in the Southwest of China. The purpose of this study is to
      investigate the anticancer activity of Lithocarpus polystachyus Rehd leaf aqueous
      extract (LPAE) and to explore the possible mechanism of its activity. Growth
      inhibition effects of LPAE breast cancer were tested in vitro and in vivo. The
      possible mechanism of its activity was analyzed with cell biological and
      molecular biological assays. After LPAE treatment, the proliferation and colony
      formation of cancer cells decreased; apoptotic cells increased; DNA
      fragmentations were evident; mRNA and protein expressions of PPARgamma, Bax, and
      caspase-3 genes increased and expressions of cyclin D1 and Bcl-2 genes decreased;
      in vivo experiment, LPAE inhibited human beast cancer growth. The findings in
      this experimental study suggested that LPAE has potential cytotoxic and apoptotic
      effects on human breast cancer cells in vitro and inhibits the cancer growth in
      vivo, and its mechanism of activity might be associated with apoptosis induction
      of cancer cells through upregulation of the mRNA and protein expressions of
      PPARgamma, Bax, and capase-3 genes and downregulation of the expressions of
      cyclin D1 and Bcl-2 genes. 

PMID- 24660969
TI  - Right ventricular isovolumic acceleration in acute pulmonary embolism.
AB  - OBJECTIVE: In this study, we examined the role of isovolumic acceleration (IVA)
      measured with right ventricle (RV) tissue Doppler imaging (TDI) to predict the
      presence of acute pulmonary embolism (APE) in hemodynamically stable patients
      with clinical suspicion of APE. MATERIALS AND METHOD: This study included 25
      hemodynamically stable (systolic blood pressure >90 mmHg) patients diagnosed with
      APE for the first time. Twenty-five subjects with similar demographic
      characteristics in whom APE was excluded due to preexisting clinical suspicion
      were also enrolled as the control group. All control group subjects were enrolled
      after proved to have no evidence of APE on imaging. Both groups were compared
      with respect to RV-IVA measured with TDI in addition to conventional
      echocardiographic parameters. RESULTS: Among the echocardiography parameters,
      only RV-IVA was impaired in patients with hemodynamically stable APE compared to
      controls (2.85 [1.37-6.42] m/sec(2) vs. 3.32 [2.24-6.52] m/sec(2) , respectively;
      P = 0.02). A receiver operating characteristic (ROC) analysis was performed to
      determine the RV-IVA value to predict clinically suspected APE. A cutoff level of
      3.22 m/sec(2) had a sensitivity of 64% and a specificity of 60%; a cutoff level
      of 3.17 m/sec(2) had a sensitivity of 64% and a specificity of 64%; and a cutoff
      level of 3.10 m/sec(2) had a sensitivity of 60% and specificity of 64% (ROC area
      under curve: 0.691, 95% CI: 0.543-0.839, P = 0.02). CONCLUSION: Results of our
      study suggest that RV-IVA may be a useful parameter to detect subtle alterations
      in RV and may predict the presence of APE in hemodynamically stable patients.

PMID- 24660970
TI  - "Risky business": a critical analysis of the role of crisis resolution and home
      treatment teams.
AB  - BACKGROUND: In 2000, the Department of Health for England recommended the
      creation of crisis resolution and home treatment teams (CRHTs) in order to reduce
      the number and length of psychiatric hospital admissions. Central to this was the
      role of gate-keeping all potential admissions. AIM: To examine the interface
      between crisis resolution and home treatment and other mental health services.
      METHODS: Semi-structured interviews with mental health professionals (n = 25) at
      eight sites within one Strategic Health Authority region. RESULTS: Despite wide
      variation in approach and provision, all teams were confronting common issues
      related to tensions at both ends of the service user trajectory - on initial
      assessment and on discharge. CONCLUSION: The CRHT model is likely to be most
      effective when there is low staff turnover, flexibility in inter-team working
      arrangements and senior practitioners have both acute and community experience.
      Rather than being seen primarily as gatekeeper to the acute service, it would be
      better to take a system approach and view the CRHT as a resource for clients
      awaiting discharge or seeking to avoid hospital admission that is equally
      available to both acute and community services.

PMID- 24660971
TI  - Activity groups for people with schizophrenia: a randomized controlled trial.
AB  - BACKGROUND: UK guidelines recommend that patients with schizophrenia are offered
      access to social activities, however, the impact of such interventions have not
      been examined in a large randomized trial. AIMS: To investigate the effect of an
      activity group intervention on mental health and global functioning 12 months
      after randomization compared to standard care alone. METHODS: Secondary analysis
      of data from the MATISSE study. Primary outcomes were global functioning,
      assessed using the Global Assessment of Functioning (GAF), and mental health
      symptoms measured using the Positive and Negative Syndrome Scale (PANSS).
      RESULTS: About 140 participants were randomized to activity groups and 137 to
      standard care alone. Follow-up data were collected from 242 (87%) participants.
      Mental health improved significantly among those offered activity groups (change
      in PANSS score = -6.0, 95% CI -2.3 to -9.8) but global functioning did not
      (change in GAF score = 0.8, 95% CI -1.7 to 3.3). No significant differences were
      found between treatment arms. CONCLUSIONS: Offering activity groups to patients
      with schizophrenia was not associated with any additional clinical benefits.
      There was poor uptake and attendance at activity groups. Interventions that aim
      to improve negative symptoms may be useful in enabling engagement in psychosocial
      interventions.

PMID- 24660972
TI  - Discrimination against people with a mental health diagnosis: qualitative
      analysis of reported experiences.
AB  - BACKGROUND: Discrimination towards people with a mental health diagnosis has
      public health implications. Recently, efforts have been made to tackle
      discrimination through campaigns and education. Understanding experiences of
      discrimination is vital in targeting efforts effectively. AIMS: The study aimed
      to explore experiences of reported discrimination described by service users in a
      national survey in England. METHOD: Structured telephone interviews were
      conducted with 537 mental health service users, randomly selected from five
      National Health Service Trusts in England. Interviews asked about experiences of
      discrimination in different life areas. Twenty-three interviews were audio
      recorded and qualitatively analysed to develop a typology of discrimination
      experiences. RESULTS: We identified seven types: organisational decisions;
      mistreatment; social distancing; stereotyping; lack of understanding;
      dismissiveness; and over-protectiveness. CONCLUSIONS: Discrimination should be
      understood as occurring within social relationships and influenced by
      expectations of contact within these relationships. A better understanding of
      these processes can help target more effective messages in anti-discrimination
      campaigns.

PMID- 24660976
TI  - Complete mitochondrial genome analysis and clinical documentation of a five
      generational Indian family with mitochondrial 1555A>G mutation and postlingual
      hearing loss.
AB  - Hearing loss is the most common sensory disorder and is genetically
      heterogeneous. Apart from nuclear gene mutations, a number of inherited
      mitochondrial mutations have also been implicated. The m.1555A>G mutation in the
      mitochondrial MT-RNR1 gene is reported as the most common mutation causing
      nonsyndromic hearing loss in various ethnic populations. We report here for the
      first time the clinical, genetic and molecular characterisation of a single large
      five-generational Tamil-speaking South Indian family with maternally inherited
      nonsyndromic postlingual hearing loss. Molecular analysis led to identification
      of m.1555A>G in 28 maternal relatives with variable degree of phenotypic
      expression. The penetrance of hearing loss among the maternal relatives in this
      family was 55%. Sequence analysis of the complete mitochondrial genome in 36
      members of this pedigree identified 25 known variants and one novel variant co
      transmitted along with m.1555A>G mutation. The mtDNA haplotype analysis revealed
      that the maternal relatives carry the R*T2 haplotype similar to Europeans and
      South Asians. Sequencing of the coding exon of GJB2 nuclear gene did not show any
      pathogenic mutations. The results suggest that other nuclear or environmental
      modifying factors could have played a role in the differential expression of
      mutation m.1555A>G in postlingual hearing loss in this family.

PMID- 24660977
TI  - Absent left main coronary artery with variation in the origin of its branches in
      a South African population.
AB  - Coronary artery anomalies are traditionally classified into anomalies of origin,
      course and termination. One of the anomalies of origin is absence of the left
      main coronary artery (LMCA), where the left anterior descending (LAD), the
      circumflex (Cx) and the ramus medianus (RM) (when present) arteries originate
      directly from the left aortic sinus. The study aimed to document the prevalence
      of absent LMCA, discuss its possible embryogenesis and clinical relevance. A
      review of 407 coronary angiograms performed by cardiologists of three private
      hospitals in the eThekwini Municipality area of KwaZulu-Natal, South Africa, was
      performed. The LMCA was absent in 9.6% (39/407) of the coronary angiograms. The
      LAD and Cx arteries originated directly from the left aortic sinus with a single
      ostium in 8.6% (35/407) and separate ostia in 1% (4/407) of the angiograms. In
      four of the angiograms with absent LMCA, a RM artery was recorded originating
      directly from the left aortic sinus in addition to the LAD and the Cx arteries.
      Angiographic detection of the anomalies of the coronary arteries is essential in
      the determination of the significance of such findings and their management. 

PMID- 24660978
TI  - The known-unknowns in spinal cord injury, with emphasis on cell-based therapies -
      a review with suggestive arenas for research.
AB  - INTRODUCTION: In spite of extensive research, the progress toward a cure in
      spinal cord injury (SCI) is still elusive, which holds good for the cell- and
      stem cell-based therapies. We have critically analyzed seven known gray areas in
      SCI, indicating the specific arenas for research to improvise the outcome of cell
      based therapies in SCI. AREAS COVERED: The seven, specific known gray areas in
      SCI analyzed are: i) the gap between animal models and human victims; ii)
      uncertainty about the time, route and dosage of cells applied; iii) source of the
      most efficacious cells for therapy; iv) inability to address the vascular
      compromise during SCI; v) lack of non-invasive methodologies to track the
      transplanted cells; vi) need for scaffolds to retain the cells at the site of
      injury; and vii) physical and chemical stimuli that might be required for
      synapses formation yielding functional neurons. EXPERT OPINION: Further research
      on scaffolds for retaining the transplanted cells at the lesion, chemical and
      physical stimuli that may help neurons become functional, a meta-analysis of
      timing of the cell therapy, mode of application and larger clinical studies are
      essential to improve the outcome.

PMID- 24660979
TI  - Tetrapositive plutonium, neptunium, uranium, and thorium coordination complexes:
      chemistry revealed by electron transfer and collision induced dissociation.
AB  - The Pu(4+), Np(4+), and U(4+) ions, which have large electron affinities of
      ~34.6, ~33.6, and ~32.6 eV, respectively, were stabilized from solution to the
      gas phase upon coordination by three neutral tetramethyl-3-oxa-glutaramide
      ligands (TMOGA). Both collision induced dissociation (CID) and electron transfer
      dissociation (ETD) of Pu(TMOGA)3(4+) reveal the propensity for reduction of
      Pu(IV) to Pu(III), by loss of TMOGA(+) in CID and by simple electron transfer in
      ETD. The reduction of Pu(IV) is in distinct contrast to retention of Th(IV) in
      both CID and ETD of Th(TMOGA)3(4+), where only the C-Oether bond cleavage product
      was observed. U(TMOGA)3(4+) behaves similarly to Th(TMOGA)3(4+) upon CID and ETD,
      while the fragmentation patterns of Np(TMOGA)3(4+) lie between those of
      Pu(TMOGA)3(4+) and U(TMOGA)3(4+). It is notable that the gas-phase fragmentation
      behaviors of these exceptional tetrapositive complexes parallel fundamental
      differences in condensed phase chemistry within the actinide series, specifically
      the tendency for reduction from the IV to III oxidation states. 

PMID- 24660981
TI  - Emesis-induced sub-periosteal haematoma: a case report.
AB  - BACKGROUND: Orbital sub-periosteal haematoma (OSH) is usually caused by orbital
      trauma. We present a case of spontaneous OSH and review the literature on this
      condition. METHODS: We present a case of sub-periosteal haematoma secondary to
      migraine and vigorous emesis. DISCUSSION: OSH is very rare; this case highlights
      the clinical features of the condition and that rapid spontaneous resolution can
      occur. We review the literature on emesis- or valsava-induced OSH and discuss
      possible mechanisms for its formation in conjunction with migraine.

PMID- 24660980
TI  - Investigating the age-related "anterior shift" in the scalp distribution of the
      P3b component using principal component analysis.
AB  - An age-related "anterior shift" in the distribution of the P3b is often reported.
      Temporospatial principal component analysis (PCA) was used to investigate the
      basis of this observation. ERPs were measured in young and old adults during a
      visual oddball task. PCA revealed two spatially distinct factors in both age
      groups, identified as the posterior P3b and anterior P3a. Young subjects
      generated a smaller P3a than P3b, while old subjects generated a P3a that did not
      differ in amplitude from their P3b. Rather than having a more anteriorly
      distributed P3b, old subjects produced a large, temporally overlapping P3a. The
      pattern of the age-related "anterior shift" in the P3 was similar for target and
      standard stimuli. The increase in the P3a in elderly adults may not represent a
      failure to habituate the novelty response, but may reflect greater reliance on
      executive control operations (P3a) to carry out the categorization/updating
      process (P3b). 

PMID- 24660982
TI  - Distribution of caveolin in the muscle spindles of human skeletal muscle.
AB  - The aim of the present study was to demonstrate the location of the different
      members of the caveolin (cav) family in human muscle spindles. Twenty spindles of
      three human muscles (vastus medialis, ischiocavernosus, bulbospongiosus) from 12
      cadavers were immunohistochemically stained for cav-1, cav-2, and cav-3, and the
      equatorial and polar regions evaluated. All layers of the outer and inner spindle
      capsule and all blood vessels within the spindle stained for cav-1 and cav-2. In
      the muscle spindle, intrafusal muscle fibres stained selectively for cav-3, but
      with a patchy appearance. Caveolinopathies may therefore also include changes in
      muscle spindle function. 

PMID- 24660983
TI  - Novel silver nanoparticle-manganese oxyhydroxide-graphene oxide nanocomposite
      prepared by modified silver mirror reaction and its application for
      electrochemical sensing.
AB  - A gas/liquid interface will be formed when the free volatilized methyl aldehyde
      gas begins to dissolve in to solution. On the basis of the traditional silver
      mirror reaction, silver nanoparticle-manganese oxyhydroxide-graphene oxide (Ag
      MnOOH-GO) nanocomposite was synthesized at the gas/liquid interface without any
      protection of inert gas at room temprature. The morphology of the nanocomposites
      could be controlled by adjusting the reaction temperature and time. The
      morphology and composition of the nanocomposites were characterized by scanning
      electron microscopy, transmission electron microscopy, X-ray diffraction, and
      Fourier transform infrared spectroscopy. The composites were then applied for
      electrochemical sensing. The electrochemical investigation for the sensor
      indicates that it has excellent property to catalyze H2O2, and could detect H2O2
      with a low detection limit of 0.2MUM and wide linear range of 0.5 MUM to 17.8 mM.
      The present study provides a general platform for the controlled synthesis of
      nanomaterials and can be extended to other optical, electronic, and magnetic
      nanocompounds. 

PMID- 24660984
TI  - Nonlinear machine learning of patchy colloid self-assembly pathways and
      mechanisms.
AB  - Bottom-up self-assembly offers a means to synthesize materials with desirable
      structural and functional properties that cannot easily be fabricated by other
      techniques. An improved understanding of the structural pathways and mechanisms
      by which self-assembling materials spontaneously form from their constituent
      building blocks is of value in understanding the fundamental principles of
      assembly and in guiding inverse building block design. We present an approach to
      infer systematically assembly pathways and mechanisms by nonlinear data mining of
      molecular simulation trajectories using diffusion maps. We have validated our
      methodology in applications to Brownian dynamics simulations of the assembly of
      anisotropic "patchy colloids" into polyhedral aggregates. For particles designed
      to form tetrahedral aggregates, we identify two divergent assembly pathways
      leading to chains of interlocking dimers and tetramers and chains of interlocking
      trigonal planar trimers. For particles designed to assemble icosahedral
      aggregates, our approach recovers two distinct assembly pathways corresponding to
      monomeric addition and budding from a disordered liquid phase. These assembly
      routes were previously reported by inspection of simulation trajectories by
      Wilber et al. ( J. Chem. Phys. 2007, 127, 085106 ; J. Chem. Phys. 2009, 131,
      175102 ), validating the capacity of our approach to systematically recover
      assembly mechanisms previously discernible only by trajectory visualization. 

PMID- 24660985
TI  - Genotype analysis in Hungarian patients with multiple primary melanoma.
AB  - Multiple primary melanoma patients (MPMps) have better prognosis and are more
      prone to genetic predisposition than single melanoma patients. We aimed to
      compare genetic background (CDKN2A, CDK4, MITF, MC1R) of 43 Hungarian MPMps with
      their clinicopathological data. We observed a higher rate of synchronous first
      and second melanoma (MM) (49%) and a higher frequency of non-melanoma tumor co
      occurrence (42%) than reported previously. CDKN2A mutation frequency was 4.7%
      (E69G, R99P). We identified a new human MC1R variant (D117G) and reported MC1R
      variant distributions in Hungarian MMs for the first time. The rare R163Q was
      exceptionally common among Hungarian MPMps, a variant otherwise frequent in Asia,
      but not in Europe. MC1R 'R' carriers showed histopathological signs of a more
      progressive disease than 'r' carriers did; however, tumor-infiltrating
      lymphocytes (TILs) in their second melanomas occurred significantly more
      frequently. Calculating 5-year overall survival, 'R' carriers showed more
      unfavourable prognosis (87%) than 'r' carriers did (95%). 

PMID- 24660986
TI  - Synthesis and characterization of aluminum-alpha-diimine complexes over multiple
      redox states.
AB  - The aluminum complexes (LMes(2-))AlCl(THF) (3) and (LDipp(-))AlCl2 (4) (LMes =
      N,N'-bis[2,4,6-trimethylphenyl]-2,3-dimethyl-1,4-diazabutadiene, LDipp = N,N'
      bis[2,6-diisopropylphenyl]-2,3-dimethyl-1,4-diazabutadiene) were prepared by
      direct reduction of the ligands with sodium metal followed by salt metathesis
      with AlCl3. The (LMes(-))AlCl2 (5) complex was prepared through one-electron
      oxidative functionalization of 3 with either AgCl or CuCl. Complex 3 was
      characterized using (1)H and (13)C NMR spectoscopies. Single-crystal X-ray
      diffraction analysis of the complexes revealed that 3-5 are all four-coordinate,
      with 3 exhibiting a trigonal pyramidal geometry, while 4 and 5 exist between
      trigonal pyramidal and tetrahedral. Notable in the LMes complexes 3 and 5 is a
      systematic lengthening of the C-Nimido bonds and shortening of the C-C bond in
      the N-C-C-N backbone with increased electron density on the ligand. The
      geometries of the complexes 3 and 5 were optimized using DFT, which showed
      primarily ligand-based frontier orbitals, supporting the analysis of the solid
      state structural data. The complexes 3-5 were also characterized by
      electrochemistry. The cyclic voltamogram of complex 3 showed an oxidation
      processes at -0.94 and -0.03 V versus ferrocene, while complexes 4 and 5 exhibit
      both reduction (-1.37 and -1.34 V, respectively) and oxidation (-0.62 and -0.73
      V, respectively) features. 

PMID- 24660987
TI  - Call for papers! A special thematic compilation/special issue crossover with ACS
      Chemical Biology, ACS Medicinal Chemistry Letters, and the Journal of Medicinal
      Chemistry focused on new frontiers in kinases.

PMID- 24660988
TI  - Organic synthesis "on water" vs "on liquids": a comparative analysis.
AB  - Several organic reactions that are accelerated under the "on water" conditions
      proceed equally well or better on other "nonsolvents" or in neat conditions.
      Alternatively, only 1 equiv of water was necessary to obtain the same
      acceleration effect testifying to the fact that the water-organic compounds
      boundary might be unnecessary to achieve the "on water"-like reactivity. 

PMID- 24660989
TI  - Free to punish: a motivated account of free will belief.
AB  - Belief in free will is a pervasive phenomenon that has important consequences for
      prosocial actions and punitive judgments, but little research has investigated
      why free will beliefs are so widespread. Across 5 studies using experimental,
      survey, and archival data and multiple measures of free will belief, we tested
      the hypothesis that a key factor promoting belief in free will is a fundamental
      desire to hold others morally responsible for their wrongful behaviors. In Study
      1, participants reported greater belief in free will after considering an immoral
      action than a morally neutral one. Study 2 provided evidence that this effect was
      due to heightened punitive motivations. In a field experiment (Study 3), an
      ostensibly real classroom cheating incident led to increased free will beliefs,
      again due to heightened punitive motivations. In Study 4, reading about others'
      immoral behaviors reduced the perceived merit of anti-free-will research, thus
      demonstrating the effect with an indirect measure of free will belief. Finally,
      Study 5 examined this relationship outside the laboratory and found that the real
      world prevalence of immoral behavior (as measured by crime and homicide rates)
      predicted free will belief on a country level. Taken together, these results
      provide a potential explanation for the strength and prevalence of belief in free
      will: It is functional for holding others morally responsible and facilitates
      justifiably punishing harmful members of society.

PMID- 24660990
TI  - Future events are far away: exploring the distance-on-distance effect.
AB  - Four dimensions of psychological distance (temporal, social, spatial, and
      probabilistic) have been widely studied. This research examines the distance-on
      distance effect where an event that is close or distal along one dimension of
      psychological distance will be judged to be close or distal along other
      dimensions. For example, individuals will perceive greater likelihood to win a
      lottery (probabilistic distance) if they sit closer to the prize (spatial
      distance). Drawing on 2 streams of findings in the construal level literature, I
      propose that this distance-on-distance effect is mediated by construal level
      induced by the known distance and only occurs when the psychological distance is
      egocentric. Five studies provide evidence supporting the basic effect, its
      underlying mechanism, and the boundary condition. These findings have important
      implications for the construal level literature, together with the research on
      distance perceptions.

PMID- 24660992
TI  - A quiet ego quiets death anxiety: humility as an existential anxiety buffer.
AB  - Five studies tested the hypothesis that a quiet ego, as exemplified by humility,
      would buffer death anxiety. Humility is characterized by a willingness to accept
      the self and life without comforting illusions, and by low levels of self-focus.
      As a consequence, it was expected to render mortality thoughts less threatening
      and less likely to evoke potentially destructive behavior patterns. In line with
      this reasoning, Study 1 found that people high in humility do not engage in self
      serving moral disengagement following mortality reminders, whereas people low in
      humility do. Study 2 showed that only people low in humility respond to death
      reminders with increased fear of death, and established that this effect was
      driven uniquely by humility and not by some other related personality trait. In
      Study 3, a low sense of psychological entitlement decreased cultural worldview
      defense in response to death thoughts, whereas a high sense of entitlement tended
      to increase it. Study 4 demonstrated that priming humility reduces self-reported
      death anxiety relative to both a baseline and a pride priming condition. Finally,
      in Study 5, experimentally induced feelings of humility prevented mortality
      reminders from leading to depleted self-control. As a whole, these findings
      obtained from relatively diverse Internet samples illustrate that the dark side
      of death anxiety is brought about by a noisy ego only and not by a quiet ego,
      revealing self-transcendence as a sturdier, healthier anxiety buffer than self
      enhancement.

PMID- 24660991
TI  - The Manhattan effect: when relationship commitment fails to promote support for
      partners' interests.
AB  - Research on close relationships has frequently contrasted one's own interests
      with the interests of the partner or the relationship and has tended to view the
      partner's and the relationship's interests as inherently aligned. The present
      article demonstrated that relationship commitment typically causes people to
      support their partner's personal interests but that this effect gets weaker to
      the extent that those interests misalign or even threaten the relationship.
      Studies 1a and 1b showed that (a) despite their strong correlation, partner
      oriented and relationship-oriented concerns in goal-directed behaviors are
      separable and (b) relationship commitment strengthens only the link between
      relationship-oriented motivation and the goal pursuit (not the link between
      partner-oriented motivation and the goal pursuit). The remaining 7 studies zero
      in on circumstances in which the partner's and the relationship's interests are
      in conflict, demonstrating that (c) relationship commitment reliably increases
      the tendency to support the partner's personal interests when those interests do
      not pose a strong threat to the relationship but that (d) this effect becomes
      weaker-and even reverses direction-as the relationship threat posed by the
      partner's interests becomes stronger. The reduction or reversal of the positive
      link between relationship commitment and propartner behaviors in such situations
      is termed the Manhattan effect. These findings suggest that the partner-versus
      relationship conflicts provide fertile ground for novel theorizing and empirical
      investigations and that relationship commitment appears to be less of a partner
      promoting construct than relationship science has suggested; instead, its role
      appears to be focused on promoting the interests of the relationship.

PMID- 24660993
TI  - Linear and nonlinear associations between general intelligence and personality in
      Project TALENT.
AB  - Research on the relations of personality traits to intelligence has primarily
      been concerned with linear associations. Yet, there are no a priori reasons why
      linear relations should be expected over nonlinear ones, which represent a much
      larger set of all possible associations. Using 2 techniques, quadratic and
      generalized additive models, we tested for linear and nonlinear associations of
      general intelligence (g) with 10 personality scales from Project TALENT (PT), a
      nationally representative sample of approximately 400,000 American high school
      students from 1960, divided into 4 grade samples (Flanagan et al., 1962). We
      departed from previous studies, including one with PT (Reeve, Meyer, & Bonaccio,
      2006), by modeling latent quadratic effects directly, controlling the influence
      of the common factor in the personality scales, and assuming a direction of
      effect from g to personality. On the basis of the literature, we made 17
      directional hypotheses for the linear and quadratic associations. Of these, 53%
      were supported in all 4 male grades and 58% in all 4 female grades. Quadratic
      associations explained substantive variance above and beyond linear effects (mean
      R2 between 1.8% and 3.6%) for Sociability, Maturity, Vigor, and Leadership in
      males and Sociability, Maturity, and Tidiness in females; linear associations
      were predominant for other traits. We discuss how suited current theories of the
      personality-intelligence interface are to explain these associations, and how
      research on intellectually gifted samples may provide a unique way of
      understanding them. We conclude that nonlinear models can provide incremental
      detail regarding personality and intelligence associations.

PMID- 24660994
TI  - Herpes simplex virus reactivation as a trigger of mucous lesions in pemphigus
      vulgaris.
AB  - BACKGROUND: Although infectious agents have long been implicated in the induction
      or exacerbation of pemphigus vulgaris (PV), a convincing role for the agent in
      the aetiology of PV has not been established. OBJECTIVES: To establish the
      association with PV and herpes simplex virus (HSV). PATIENTS AND METHODS: We
      examined saliva for the presence of HSV DNA after the onset of PV initially
      localized to the oral lesions in addition to conventional serological tests and
      immunohistochemistry. RESULTS: We successfully detected high levels of HSV DNA in
      the saliva samples from six of 16 patients with PV at the earliest stage, who had
      no episodes of herpes simplex. The prevalence (37.5%) of detecting HSV DNA in the
      patients with PV was lower than that of eczema herpeticum (56.5%), but comparable
      to that in patients with herpes labialis (30.0%). Copy numbers of the HSV DNA
      were rather higher than those with herpes labialis and with eczema herpeticum. In
      general, detection of HSV DNA in saliva was transient and restricted to the
      earliest phase of the disease. In addition, anti-HSV immunoglobulin (Ig) G titres
      in patients with PV were significantly higher than those in patients with
      virologically confirmed HSV-induced disorders. All salivary HSV DNA-positive
      patients with PV had run a more complex, intractable course refractory to
      conventional therapy. CONCLUSIONS: Detection of HSV DNA in saliva is a useful and
      noninvasive, quantitative method for establishing the role of HSV in the
      pathogenesis of PV and for identifying individuals at greater risk for
      subsequently developing refractory PV.

PMID- 24660995
TI  - Combined therapeutic effects of vinblastine and Astragalus saponins in human
      colon cancer cells and tumor xenograft via inhibition of tumor growth and
      proangiogenic factors.
AB  - Our previous study had demonstrated that Astragalus saponins (AST) could reduce
      the side effects of orthodox chemotherapeutic drugs, while concurrently promote
      antitumor activity. In the present study, we attempted to investigate the
      potential synergistic anticarcinogenic effects of AST and a vinca alkaloid
      vinblastine (VBL). Reduced expression of key proangiogenic and metastatic factors
      including VEGF, bFGF, metalloproteinase (MMP)-2, and MMP-9 was detected in VBL
      treated colon cancer cells, with further downregulation by combined VBL/AST
      treatment. Subsequently, VBL or AST decreased LoVo cell invasiveness, with
      further reduction when the drugs were cotreated. Significant growth inhibition
      and cell cycle arrest at G2/M phase were achieved by either drug treatment with
      apparent synergistic effects. VBL-induced apoptosis was confirmed but found to be
      unrelated to induction of the novel apoptotic protein NSAID-activated gene 1. In
      vivo study in tumor xenograft indicates that combined VBL/AST treatment resulted
      in sustained regression of tumor growth, with attenuation of the neutropenic and
      anemic effects of VBL. In addition, downregulation of proangiogenic and
      proliferative factors was also visualized, with boosting effect by combined drug
      treatment. These findings have provided evidence that AST combined with adjuvant
      chemotherapeutics like VBL could alleviate cancer development through diversified
      modes of action, including the regulation of angiogenesis. 

PMID- 24660997
TI  - Corrigendum to 'An orthotropic viscoelastic material model for passive
      myocardium: theory and algorithmic treatment'.

PMID- 24660996
TI  - Effect of increased severity of mitral regurgitation and preprocedural right
      ventricular systolic dysfunction on biventricular and left atrial mechanical
      functions following percutaneous mitral balloon valvuloplasty.
AB  - BACKGROUND: Severe mitral stenosis (MS) may impair left atrial (LA) pump
      function, and increase LA and pulmonary venous pressure resulting in right
      ventricular (RV) systolic dysfunction. The aim of this study was to evaluate
      biventricular and LA function after percutaneous mitral balloon valvuloplasty
      (PMBV) by tissue Doppler (TDI) and speckle tracking echocardiography (STE).
      METHODS: Twenty-eight consecutive patients with severe symptomatic rheumatic MS
      (11 men, mean age: 39 +/- 7 years) who were referred for PMBV were included in
      the study. In addition to conventional echocardiography, all patients underwent
      TDI and two-dimensional (2D) (STE) to assess left ventricular (LV), LA, and RV
      function before and 3 months after PMBV. Severity of mitral regurgitation (MR)
      was graded by the ratio of MR jet area to LA area (JA/LAA) method and any
      postprocedural progression of the JA/LAA ratio was defined as worsening of MR.
      Peak systolic velocity of tricuspid lateral annulus (RVs) <11.5 cm/sec was
      accepted as RV dysfunction. RESULTS: Left atrial diameter and area were
      decreased, while LV dimensions were unchanged following the valvuloplasty. PMBV
      improved STE-based LV mechanical indices, LA reservoir and conduit function, and
      RV free wall basal longitudinal strain (LS) and displacement. Increased severity
      of MR was detected in 6 patients, and PMBV did not improve the STE-based RV or LV
      function in these patients, while LA reservoir and conduit function were both
      improved independent of MR worsening. There was significant improvement in RVs
      and RV basal LS in the 15 patients with preprocedural RV systolic dysfunction,
      while the improvement in patients with normal preprocedural RV function was not
      significant. CONCLUSION: Percutaneous mitral balloon valvuloplasty may improve
      both LA and biventricular function in patients with severe symptomatic MS. Both
      TDI and STE are useful to determine biventricular and LA function after PMBV.
      Although the number of patients was insufficient, worsening of MR after PMBV may
      limit the improvement in RV and LV function, while preprocedural RV dysfunction
      does not seem to limit the improvement in RV function and pulmonary artery
      systolic pressure. Large scale follow-up studies are required to see whether the
      changes observed in cardiac mechanics are persistent.

PMID- 24660998
TI  - Lower eyelid involutional entropion repair with lateral tarsal strip and
      infraciliary rotation sutures: surgical technique and outcomes.
AB  - PURPOSE: To describe a novel technique for the surgical repair of involution
      entropion of the lower eyelid and to evaluate its effectiveness in a series of
      patients. METHODS: This retrospective interventional case series includes
      patients who underwent entropion repair via lateral tarsal strip with
      infraciliary rotation sutures during a 5-year period by one surgeon. Demographic
      data was collected and incidence of recurrence was determined. RESULTS: Forty
      four eyelids of 36 patients with involutional entropion underwent surgical repair
      via lateral tarsal strip plus infraciliary rotation sutures. All patients had
      successful repair of entropion with no recurrences recorded on follow-up, which
      ranged from 1 to 67 months. CONCLUSIONS: Lateral tarsal strip combined with
      infraciliary rotation sutures is a successful method for the repair of involution
      entropion of the lower eyelid.

PMID- 24660999
TI  - Intradetrusor onabotulinumtoxinA for overactive bladder.
AB  - INTRODUCTION: Overactive bladder is a life-compromising disease that affects
      approximately 11.8% of all men and women, with increasing rates in the elderly.
      The mainstay of pharmacotherapy for this disease, anticholinergics, has up to a
      71% discontinuation rate at 6 months. The emerging data of intradetrusor
      onabotulinumtoxinA (onabotA) use for treatment of idiopathic overactive bladder
      is showing to be an efficacious and well-tolerated alternative to the mainstay of
      therapy. AREAS COVERED: This study covers the use of onabotA and its use for
      idiopathic overactive bladder, stemming from its use in neurogenic detrusor
      overactivity, by evaluating the conclusions of current studies. A literature
      search and review was carried out for onabotA in treatment of overactive bladder
      using PubMed. EXPERT OPINION: Multiple randomized clinical trials have shown that
      intradetrusor injection with onabotA is effective in treating non-neurogenic
      bladder with promising efficacy in patients who have failed traditional
      pharmacotherapy. This treatment may be superior in certain patients due to its
      higher rate of compliance and higher rates of complete symptom resolution. Long
      term studies are needed.

PMID- 24661000
TI  - The effects of motivating interventions on rehabilitation outcomes in children
      and youth with acquired brain injuries: a systematic review.
AB  - PRIMARY OBJECTIVE: To systematically review the evidence of the effects of
      motivating rehabilitation interventions on outcomes in children with acquired
      brain injury (ABI). METHODS: A literature search of six databases was conducted
      to identify intervention studies published until July 2013. The American Academy
      for Cerebral Palsy and Developmental Medicine (AACPDM) systematic review
      methodology was used as a framework. Two reviewers independently extracted data
      and assessed level of evidence and quality of studies. RESULTS: Of 891 records
      initially retrieved, 166 were screened by abstract and 31 by full text; 10
      studies comprised of five randomized controlled trials, two case series and three
      single subject research design studies met the inclusion criteria. Studies fell
      into three intervention categories: (1) token economy based interventions; (2)
      virtual reality (VR); and (3) memory and attention interventions. CONCLUSIONS: A
      paucity of evidence has examined the effects of rehabilitation interventions with
      a motivational component. Token economies can significantly enhance memory and
      response inhibition performance in children with ABI. VR systems are motivating,
      yet findings are limited by the lack of use and availability of psychometrically
      evaluated measures of motivation. Findings point to the need for further research
      to evaluate the effects of motivation-based interventions.

PMID- 24661002
TI  - Combined ab initio molecular dynamics and experimental studies of carbon atom
      addition to benzene.
AB  - Car-Parrinello molecular dynamics was used to explore the reactions between
      triplet and singlet carbon atoms with benzene. The computations reveal that, in
      the singlet C atom reaction, products are very exothermic where nearly every
      collision yields a product that is determined by the initial encounter geometry.
      The singlet C atom reaction does not follow the minimum energy path because the
      bimolecular reaction is controlled by dynamics (i.e., initial orientation of
      encounter). On the other hand, in a 10 K solid Ar matrix, ground state C((3)P)
      atoms do tend to follow RRKM kinetics. Thus, ab initio molecular dynamics (AIMD)
      results indicate that a significant fraction of C-H insertion occurs to form
      phenylcarbene whereas, in marked contrast to previous theoretical and
      experimental conclusions, the Ar matrix isolation studies indicate a large
      fraction of direct cycloheptatetraene formation, without the intermediacy of
      phenylcarbene. The AIMD calculations are more consistent with vaporized carbon
      atom experiments where labeling studies indicate the initial formation of
      phenylcarbene. This underlines that the availability of thermodynamic sinks can
      completely alter the observed reaction dynamics. 

PMID- 24661001
TI  - A common atopy-associated variant in the Th2 cytokine locus control region
      impacts transcriptional regulation and alters SMAD3 and SP1 binding.
AB  - BACKGROUND: Type 2 immune responses directed by Th2 cells and characterized by
      the signature cytokines IL4, IL5, and IL13 play major pathogenic roles in atopic
      diseases. Single nucleotide polymorphisms in the human Th2 cytokine locus in
      particular in a locus control region within the DNA repair gene RAD50, containing
      several RAD50 DNase1-hypersensitive sites (RHS), have been robustly associated
      with atopic traits in genome-wide association studies (GWAS). Functional variants
      in IL13 have been intensely studied, whereas no causative variants for the IL13
      independent RAD50 signal have been identified yet. This study aimed to
      characterize the functional impact of the atopy-associated polymorphism rs2240032
      located in the human RHS7 on cis-regulatory activity and differential binding of
      transcription factors. METHODS: Differential transcription factor binding was
      analyzed by electrophoretic mobility shift assays (EMSAs) with Jurkat T-cell
      nuclear extracts. Identification of differentially binding factors was performed
      using mass spectrometry (LC-MS/MS). Reporter vector constructs carrying either
      the major or minor allele of rs2240032 were tested for regulating transcriptional
      activity in Jurkat and HeLa cells. RESULTS: The variant rs2240032 impacts
      transcriptional activity and allele-specific binding of SMAD3, SP1, and
      additional putative protein complex partners. We further demonstrate that
      rs2240032 is located in an RHS7 subunit which itself encompasses repressor
      activity and might be important for the fine-tuning of transcription regulation
      within this region. CONCLUSION: The human RHS7 critically contributes to the
      regulation of gene transcription, and the common atopy-associated polymorphism
      rs2240032 impacts transcriptional activity and transcription factor binding.

PMID- 24661003
TI  - Presence and distribution of urocortin and its receptors in the epididymis of
      alpaca (Vicugna pacos).
AB  - Urocortin 1 (UCN) is a 40-amino acid peptide belonging to the corticotrophin
      releasing hormone (CRH) family. The biological effects of this peptide are
      modulated by binding two G-coupled receptors named CRH receptor 1 (CRHR1) and CRH
      receptor 2 (CRHR2). CRHR2 has high affinity for UCN. The aim of the present study
      was to investigate the presence and distribution of UCN, CRHR1 and CRHR2 in the
      epididymis of the South America camelid Alpaca (Vicugna pacos) by Western
      blotting analysis and immunohistochemistry. Tissue extracts of the organ reacted
      with the anti-UCN, anti-CRHR1 and anti-CRHR2 antibodies, recognizing in all the
      cases a single specific protein band. UCN- and CRHR2-immunoreactivities (IRs)
      were found in the cytoplasm of the principal cells (PCs) of the caput epididymis.
      A prevalent supranuclear localization of granular-shaped positive material was
      observed. CRHR1-IR was observed in the fibromuscular stromal cells encircling the
      tubules and in the smooth musculature of the blood vessels throughout the three
      epididymal segments. In addition, in the cauda, CRHR1-IR was observed in some
      apical epithelial cells (ACs) which were morphologically similar to apical
      mitochondria-rich cells (AMRCs). These results suggest that UCN, CRHR1 and CRHR2
      are expressed in the alpaca epididymis and that CRH-related peptides might play
      multiple roles in maturation and storage of spermatozoa. 

PMID- 24661004
TI  - LRRK2: dropping (kinase) inhibitions and seeking an (immune) response.

PMID- 24661005
TI  - TLR2 and TLR4 expression in atopic dermatitis, contact dermatitis and psoriasis.
AB  - The aim of the study was to investigate the expression of Toll-like receptors
      (TLRs) 2 and 4 on keratinocytes in atopic dermatitis, contact dermatitis, and
      psoriasis by PCR and by immunohistochemistry including confocal microscopy.
      Confocal microscopy revealed a granular intra-cellular expression pattern for TLR
      2 and a homogenous intra-cellular expression pattern for TLR 4 in normal and
      diseased skin. TLR 2 was constitutively expressed in the suprabasal layers in
      normal skin, but limited to the basal epidermis in diseased skin. TLR 4
      expression was concentrated to the basal layers in normal skin, whereas it was
      pronounced in upper layers in diseased skin. The shift in the TLR expression may
      be related to the disturbed skin barrier and a need for enhanced immune
      surveillance because of invading microbes. Also, there must be a balance between
      sufficient immune response and overstimulation. 

PMID- 24661006
TI  - Concentration dependence of the dielectric permittivity, structure, and dynamics
      of aqueous NaCl solutions: comparison between the Drude oscillator and electronic
      continuum models.
AB  - We report molecular dynamics simulations of aqueous sodium chloride solutions at
      T = 298 K and p = 1 bar in order to investigate the salt concentration dependence
      of the dielectric permittivity, the structure, and the dynamical properties.
      Different models were applied up to 7 m salt concentration: the Drude oscillator
      model with a negative Drude particle (SWM4-NDP), the TIP4P/2005-Reif
      nonpolarizable model, and an electronic continuum polarizable model (MDEC). Both
      SWM4-NDP and MDEC polarizable models were able to quantitatively reproduce the
      concentration dependence of the dielectric permittivity of NaCl aqueous
      solutions. On the contrary, the nonpolarizable TIP4P/2005 water model failed to
      quantitatively predict this concentration dependence. In contrast with the SWM4
      NDP model, the MDEC model was unable to capture the concentration dependence of
      the structure and the dynamics of NaCl solutions. The SWM4-NDP model proved to be
      the most efficient polarizable model to reproduce quantitatively the
      concentration dependence of the dielectric permittivity, the dynamics, and the
      structure of NaCl solutions. 

PMID- 24661008
TI  - Family of defect-dicubane Ni4Ln2 (Ln = Gd, Tb, Dy, Ho) and Ni4Y2 complexes: rare
      Tb(III) and Ho(III) examples showing SMM behavior.
AB  - Reactions of Ln(III) perchlorate (Ln = Gd, Tb, Dy, and Ho), NiCl2.6H2O, and a
      polydentate Schiff base resulted in the assembly of novel isostructural
      hexanuclear Ni4Ln2 complexes [Ln = Gd (1), Tb (2), Dy (3), Ho (4)] with an
      unprecedented 3d-4f metal topology consisting of two defect-dicubane units. The
      corresponding Ni4Y2 (5) complex containing diamagnetic Y(III) atoms was also
      isolated to assist the magnetic studies. Interestingly, complexes 2 and 3 exhibit
      SMM characteristics and 4 shows slow relaxation of the magnetization. The absence
      of frequency-dependent in-phase and out-of-phase signals for the Ni-Y species
      suggests that the Ln ions' contribution to the slow relaxation must be effectual
      as previously observed in other Ni-Dy samples. However, the observation of chi"
      signals with zero dc field for the Ni-Tb and Ni-Ho derivatives is notable.
      Indeed, this is the first time that such a behavior is observed in the Ni-Tb and
      Ni-Ho complexes. 

PMID- 24661007
TI  - A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell
      proliferation, migration, and invasion.
AB  - Signal transducer and activator of transcription 3 (STAT3) plays important roles
      in multiple aspects of cancer aggressiveness including migration, invasion,
      survival, self-renewal, angiogenesis, and tumor cell immune evasion by regulating
      the expression of multiple downstream target genes. STAT3 is constitutively
      activated in many malignant tumors and its activation is associated with high
      histological grade and advanced cancer stages. Thus, inhibiting STAT3 promises an
      attracting strategy for treatment of advanced and metastatic cancers. Herein, we
      identified a STAT3 inhibitor, inS3-54, by targeting the DNA-binding domain of
      STAT3 using an improved virtual screening strategy. InS3-54 preferentially
      suppresses proliferation of cancer over non-cancer cells and inhibits migration
      and invasion of malignant cells. Biochemical analyses show that inS3-54
      selectively inhibits STAT3 binding to DNA without affecting the activation and
      dimerization of STAT3. Furthermore, inS3-54 inhibits expression of STAT3
      downstream target genes and STAT3 binding to chromatin in situ. Thus, inS3-54
      represents a novel probe for development of specific inhibitors targeting the DNA
      binding domain of STAT3 and a potential therapeutic for cancer treatments. 

PMID- 24661009
TI  - Rheology and electrospinning of regenerated bombyx mori silk fibroin aqueous
      solutions.
AB  - Bombyx mori silk fibroin (BMSF) has received considerable research interest as a
      potential biomaterial owing to its excellent mechanical properties and benign,
      versatile material fabrication options, including electrospinning. Despite this,
      characterizations of regenerated BMSF aqueous solutions and electrospun materials
      resulting from them are still very limited in the literature. This report details
      the rheological characterization of regenerated aqueous BMSF solutions under
      shear and elongational deformation. Well-characterized regenerated BMSF solutions
      were then systematically electrospun over a range of concentrations and process
      parameters to determine their effects on electrospinning processing windows and
      fiber morphology. BMSF solutions could not be electrospun successfully if BMSF
      concentration was below 20 wt % or the relaxation time measured using the CaBER
      rheometer was below 0.001 s. Electrospun BMSF fiber diameter was found to
      increase with solution concentration when stable electrospinning was achieved. An
      upper threshold of 30 wt % BMSF solution was identified for the formation of
      fibers with a circular cross section. Adding small amount of high molecular
      weight poly(ethylene oxide) was an effective rheological modifier that greatly
      improved the electrospinnability of BMSF solutions. Electrospinning BMSF-PEO
      solutions over a range of parameters significantly altered the fiber products.
      Increasing voltage from 0.5 to 1 kV/cm was found to decrease fiber diameter by
      approximately 50% (p < 0.001). Flow rate was found to have a significant effect
      on fiber diameter, which decreased with spinneret height. The results presented
      here provide valuable guidance in the production of BMSF electrospun materials
      with specific properties for tissue engineering and regenerative medicine. 

PMID- 24661010
TI  - Highly versatile Pd-thioether-phosphite catalytic systems for asymmetric allylic
      alkylation, amination, and etherification reactions.
AB  - A Pd-furanoside thioether-phosphite catalytic system that can create new C-C, C
      N, and C-O bonds in several substrate types using a wide range of nucleophiles in
      high yields and enantioselectivities has been identified. Of particular note are
      the excellent enantioselectivities obtained in the etherification of linear and
      cyclic substrates. The potential application of the new Pd-thioether-phosphite
      catalytic systems was also demonstrated by the synthesis of the chiral carbo- and
      heterocycles. 

PMID- 24661011
TI  - Impaired right and left ventricular function in asymptomatic children with
      repaired tetralogy of Fallot by two-dimensional speckle tracking echocardiography
      study.
AB  - BACKGROUND: Early detection of right ventricular (RV) and left ventricular (LV)
      dysfunction in patients with repaired tetralogy of Fallot (TOF) is essential
      because dysfunction is correlated with a poor clinical outcome. The aim of this
      study was to assess RV and LV function in asymptomatic children with repaired TOF
      by two-dimensional ultrasound speckle tracking echocardiography (STE). METHODS:
      Fifty-six asymptomatic children with a preserved biventricular ejection fraction
      (EF) after repair of TOF and 35 healthy control subjects were studied. RV and LV
      strain and strain rate were measured by STE. RVEF and pulmonary regurgitation
      (PR) were assessed using cardiac magnetic resonance imaging. RESULTS: Compared
      with the control subjects, RV regional longitudinal strain and strain rate and
      global longitudinal strain (GLS) and strain rate (GLSR) were impaired in children
      with repaired TOF. Likewise, LV circumferential and radial strain and strain rate
      were reduced in patients with TOF. In contrast, longitudinal strain and strain
      rate did not differ between the groups. RV and LV GLSR were correlated with
      postoperative follow-up period (r1 = -0.44; r2 = -0.48). RV GLS and GLSR were
      associated with RVEF (r1 = 0.64; r2 = 0.60) and PR (r1 = -0.48; r2 = -0.49). LV
      circumferential strain rate was related to PR (r = -0.45). CONCLUSIONS: STE can
      identify abnormalities that may represent early impairment of RV and LV systolic
      function in postoperative TOF patients with a preserved EF. PR is associated with
      decreased biventricular performance in repaired patients. STE-derived strain and
      strain rate may be useful indices for detecting the early deterioration of
      biventricular performance in patients with TOF.

PMID- 24661012
TI  - Occurrence of enteropathogenic bacteria in urban pigeons (Columba livia) in
      Italy.
AB  - This study was aimed at evaluating the prevalence of Campylobacter spp.,
      Escherichia coli O157, Salmonella spp., and related virulence factors (the cdt,
      stx, and eae genes) in urban pigeons of the coastal area of the Campania region
      (southern Italy). To achieve this goal, cloacal swab samples from a total of 1800
      urban pigeons were collected and subjected to culture methods, PCR, and
      serotyping. The results of the present study showed a prevalence of 48.3%
      (870/1800), 7.8% (141/1800), and 0.9% (16/1800), for C. jejuni, E. coli O157, and
      S. Typhimurium, respectively. All C. jejuni isolates (870/870) carried cdt genes,
      whereas all E. coli O157 isolates carried stx genes, and 14.9% (21/141) carried
      the eae gene. These findings clearly show that urban pigeons in the coastal area
      of the Campania region may constitute an environmental reservoir of these
      pathogens, thus representing a source of infection for other birds, livestock,
      and humans.

PMID- 24661013
TI  - Peripheral blood 8 colour flow cytometry monitoring of hairy cell leukaemia
      allows detection of high-risk patients.
AB  - Although purine analogues have significantly improved the outcome of hairy cell
      leukaemia (HCL) patients, 30-40% relapse, illustrating the need for minimal
      residual disease (MRD) markers that can aid personalized therapeutic management.
      Diagnostic samples from 34 HCL patients were used to design an 8-colour flow
      cytometry (8-FC) tube for blood MRD (B/RD) analysis (188 samples) which was
      compared to quantitative IGH polymerase chain reaction (Q-PCR) on 83 samples and
      to qualitative consensus IGH PCR clonality analysis on 165 samples. Despite
      heterogeneous HCL phenotypes at diagnosis, discrimination from normal B
      lymphocytes was possible in all cases using a single 8-FC tube, with a robust
      sensitivity of detection of 10(-4) , comparable to Q-PCR at this level, but
      preferable in terms of informativeness, simplicity and cost. B/RD assessment of
      15 patients achieving haematological complete remission after purine analogues
      was predictive of a clinically significant relapse risk: with a median follow-up
      of 95 months; only one of the nine patients with reproducible 8-FC B/RD levels
      below 10(-4) (B/RD(neg) ) relapsed, compared to 5/6 in the B/RD(pos) group (P =
      0.003). These data demonstrate the clinical interest of a robust 8-FC HCL B/RD
      strategy that could become a surrogate biomarker for therapeutic stratification
      and new drug assessment, which should be evaluated prospectively.

PMID- 24661015
TI  - pH oscillations and mechanistic analysis in the hydrogen peroxide-sulfite
      thiourea reaction system.
AB  - A new pH oscillator has been constructed by combining the pH clock reaction H2O2
      SO3(2-)-H(+) with thiourea (Tu, (NH2)2CS) as a proton-consuming species. The
      system exhibited oligo-oscillatory behavior in a closed system, and large
      amplitude oscillations in a continuous-flow stirred tank reactor (CSTR) were
      observed in a narrow range of input concentrations, flow rate, and temperature.
      For the purpose of constructing the kinetic model, a reversed-phase ion-pair high
      performance liquid chromatography (HPLC) and mass spectrometer (MS) were used to
      track and determine intermediate species during the oxidation of thiourea by
      hydrogen peroxide. Experimental results illustrated that the four species:
      thiourea monoxide (TuO), formamidine disulfide (Tu2(2+)), thiourea dioxide
      (TuO2), and thiourea trioxide (TuO3) were formed during the oxidation process. A
      ten-step mechanistic model was proposed, where TuO was another key species
      participating in two proton feedback loops in addition to bisulfite. Numerical
      simulations based on this model agreed well with the experimental results. 

PMID- 24661014
TI  - Developing questionnaires for educational research: AMEE Guide No. 87.
AB  - In this AMEE Guide, we consider the design and development of self-administered
      surveys, commonly called questionnaires. Questionnaires are widely employed in
      medical education research. Unfortunately, the processes used to develop such
      questionnaires vary in quality and lack consistent, rigorous standards.
      Consequently, the quality of the questionnaires used in medical education
      research is highly variable. To address this problem, this AMEE Guide presents a
      systematic, seven-step process for designing high-quality questionnaires, with
      particular emphasis on developing survey scales. These seven steps do not address
      all aspects of survey design, nor do they represent the only way to develop a
      high-quality questionnaire. Instead, these steps synthesize multiple survey
      design techniques and organize them into a cohesive process for questionnaire
      developers of all levels. Addressing each of these steps systematically will
      improve the probabilities that survey designers will accurately measure what they
      intend to measure.

PMID- 24661016
TI  - Characterization of Weissella ceti infections in Brazilian rainbow trout,
      Oncorhynchus mykiss (Walbaum), farms and development of an oil-adjuvanted
      vaccine.
AB  - Weissella ceti is an emerging bacterial pathogen that affects rainbow trout,
      Oncorhynchus mykiss (Walbaum), farms. The aims of this study were to genotype W.
      ceti strains isolated from distinct geographical origins and to determine the
      efficacy of an oil-adjuvanted vaccine against the disease. Between 2010 and 2012,
      outbreaks were recorded in five Brazilian farms, and 34 W. ceti isolates were
      genetically characterized by repetitive extragenic palindromic PCR,
      enterobacterial repetitive intergenic consensus sequences PCR and pulsed-field
      gel electrophoresis. Two different W. ceti vaccines were tested: an aqueous-based
      whole-cell inactivated vaccine (bacterin) and oil-adjuvanted vaccine. Their
      efficacy was evaluated in rainbow trout at 30 and 60 days post-vaccination
      (d.p.v.). W. ceti was found to be a highly homogeneous population in Brazil, with
      clonally related genotypes. Oil-adjuvanted vaccine exhibited the best (P < 0.05)
      protection against disease, reaching relative percentage survival (RPS)values of
      92% at 30 and 60 d.p.v. Bacterin resulted in RPS values of 67% and 58% at day 30
      and 60, respectively. The oil-adjuvanted vaccine provided effective protection
      against W. ceti infection in rainbow trout. 

PMID- 24661017
TI  - Motor dysfunction and behavioural problems frequently coexist with congenital
      heart disease in school-age children.
AB  - AIM: Patients with congenital heart disease are at risk of neurodevelopmental
      deficits. Impairments in motor and behavioural function occur frequently, but no
      information is available concerning the coexistence of deficits in these two
      developmental domains. This study explored the occurrence of motor and
      behavioural deficits and their coexistence in children with surgically corrected
      congenital heart disease. METHODS: Outcome was assessed in 95 children with
      congenital heart disease who had undergone cardiopulmonary bypass surgery. Their
      mean age was 9.6 years (SD 2.5). Motor function was assessed with the Zurich
      Neuromotor Assessment and behaviour with the Strength and Difficulties
      Questionnaire. RESULTS: Children with congenital heart disease performed poorer
      in all motor domains compared with the reference population (all p <= 0.001).
      Behaviour was affected in the domains 'emotional symptoms' and
      'hyperactivity/inattention' (both p < 0.01), and 54% of the children with motor
      abnormalities showed behavioural deficits. Children with coexistent abnormalities
      in behaviour and motor function had higher rates of remedial school services and
      therapeutic support. CONCLUSION: Children with congenital heart disease are at
      risk of long-term motor and behavioural problems, and there is a high rate of
      coexistence of problems in both domains. Early and longitudinal assessment of all
      developmental domains is necessary to provide adequate early support.

PMID- 24661018
TI  - Enantiomerically pure lanthanide-organic polytungstates exhibiting two-photon
      absorption properties.
AB  - Two enantiomerically pure polytungstates,
      Na2[(CH3)2NH2]3{Na?[Ce(III)(H2O)(CH3CH2OH)(L-tartH3)(H2Si2W19O66)]}.3.5H2O (L-1)
      and [(CH3)2NH2]7{Na?[Ce(III)(H2O)(CH3CH2OH)(D-tartH3)(Si2W19O66)]}.2.5H2O (D-1),
      were successfully synthesized. Structural analysis indicates that chiral tartrate
      ligands directly connect with novel lacunary [Si2W19O66](10-) polytungstate
      units. Strong induced optical activity in the polyoxometalate (POM) units is
      manifested by circular dichroism spectroscopy. Z-scan analysis revealed that L-1
      and D-1 are the first chiral POM-based complexes that exhibit two-photon
      absorption properties typical of the third-order nonlinear optical response.

PMID- 24661019
TI  - The beneficial effect of acromegaly control on blood pressure values in
      normotensive patients.
AB  - OBJECTIVE: Control of acromegaly may ameliorate blood pressure (BP) in
      hypertensive (HT) patients. We evaluated the impact of acromegaly control on BP
      values of normotensive (NT) acromegalics. DESIGN: Retrospective cohort study.
      PATIENTS: Fifty-eight naive patients with acromegaly (39 F; age range, 30-69
      years), including 28 NT and 30 HT subjects, participated in the study.
      MEASUREMENTS: Blood pressure was measured by clinical measurement and 24-h
      ambulatory monitoring at diagnosis and after 24 months of medical therapy for
      acromegaly. RESULTS: Acromegaly was controlled by medical therapy in 15 NT and 17
      HT patients at 24 months. In the NT group, systolic (SBP) or diastolic (DBP) BP
      significantly increased (all P < 0.005) when acromegaly was uncontrolled, but did
      not change when the disease was controlled. Changes in SBP and DBP were also
      significantly different between uncontrolled and controlled NT patients. At 24
      months, clinical hypertension was detected only in uncontrolled NT patients (46%
      vs 0%, P < 0.001), whereas ambulatory hypertension was found in 38% of
      uncontrolled and in 7% of controlled NT subjects (P = 0.035). In the HT group,
      ambulatory SBP increased in patients with uncontrolled acromegaly (24-h SBP P =
      0.046, day SBP P = 0.005, night SBP P = 0.005), whereas ambulatory DBP decreased
      in subjects with controlled disease (24-h DBP P = 0.008, day DBP P = 0.026).
      CONCLUSIONS: Control of acromegaly has a beneficial effect on BP regulation
      either in HT or NT subjects; in the latter, it may prevent progression towards
      hypertension.

PMID- 24661020
TI  - Phenotypic alterations, clinical impact and therapeutic potential of regulatory T
      cells in cancer.
AB  - INTRODUCTION: Regulatory T cells (Tregs) have been characterised in different
      cancers. They accumulate in peripheral blood and tumour microenvironments where
      they suppress tumour-specific immune responses, enabling tumours to develop
      without challenge. This tumour immune evasion represents a major obstacle to
      successful cancer therapies. Whilst Tregs are generally divided into thymic
      derived and peripherally induced, Tregs exhibit a wide spectrum of phenotypes and
      functional capacity dependent on microenvironment. This phenotypic diversity is
      also reflected in tumour-infiltrating Treg (TI Treg) populations, which may
      explain the variable impact of Treg accumulation on prognosis in different
      cancers. Identifying TI Treg subsets is critical to understand TI Treg biology
      and for developing effective immunotherapies. AREAS COVERED: This review
      discusses current and potential markers, and the modulation of these markers in
      cancer. In addition, we systematically review the clinical impact of Tregs in
      cancer and their potential as a therapeutic target, with a focus on TI Tregs.
      EXPERT OPINION: TI Tregs represent dynamic and diverse subsets that are key in
      promoting tumour progression through their suppressive activities. Targeting
      specific TI Treg subpopulations and functional TI Treg markers represents a
      feasible therapeutic strategy that might allow reestablishment of antitumour
      immune responses without affecting physiological immune regulation.

PMID- 24661021
TI  - Multistage unfolding of an SH3 domain: an initial urea-filled dry molten globule
      precedes a wet molten globule with non-native structure.
AB  - The unfolding of the SH3 domain of the PI3 kinase in aqueous urea has been
      studied using a synergistic experiment-simulation approach. The experimental
      observation of a transient wet molten globule intermediate, IU, with an unusual
      non-native burial of the sole Trp residue, W53, provides the benchmark for the
      unfolding simulations performed (eight in total, each at least 0.5 MUs long). The
      simulations reveal that the partially unfolded IU ensemble is preceded by an
      early native-like molten globule intermediate ensemble I*. In the very initial
      stage of unfolding, dry globule conformations with the protein core filled with
      urea instead of water are transiently observed within the I* ensemble. Water
      penetration into the urea-filled core of dry globule conformations is frequently
      accompanied by very transient burial of W53. Later during gradual unfolding, W53
      is seen to again become transiently buried in the IU ensemble for a much longer
      time. In the structurally heterogeneous IU ensemble, conformational flexibility
      of the C-terminal beta-strands enables W53 burial by the formation of non-native,
      tertiary contacts with hydrophobic residues, which could serve to protect the
      protein from aggregation during unfolding. 

PMID- 24661022
TI  - Comparison between mechanical stress and bone mineral density in the femur after
      total hip arthroplasty by using subject-specific finite element analyses.
AB  - The mechanism underling bone mineral density (BMD) loss that occurs in the femur
      after total hip arthroplasty (THA) remains unknown. We compared the equivalent
      stress and strain energy density (SED) to BMD in the femur after THA using
      subject-specific finite element analyses. Twenty-four patients who had undergone
      primary cementless THA were analysed. BMD was measured using dual-energy X-ray
      absorptiometry (DEXA) at 1 week and 3, 6 and 12 months after THA. Seven regions
      of interest (ROIs) were defined in accordance with Gruen's system (ROIs 1-7).
      Computed tomography images of the femurs were acquired pre- and postoperatively,
      and the images were converted into three-dimensional finite element (FE) models.
      Equivalent stress and SED were analysed and compared with DEXA data. BMD was
      maintained 1 year after THA in ROIs 3, 4, 5 and 6, whereas BMD decreased in ROIs
      1, 2 and 7. FE analysis revealed that equivalent stress in ROIs 3, 4, 5 and 6 was
      much higher than that in ROIs 1, 2 and 7. A significant correlation was observed
      between the rate of changes in BMD and equivalent stress. Reduction of equivalent
      stress may contribute to decrease in BMD in the femur after THA.

PMID- 24661023
TI  - Microscopic evidence of the opportunistic reproductive strategy and early sexual
      maturation of the small-sized characin Knodus moenkhausii (Characidae, Pisces).
AB  - We investigated the reproductive biology of Knodus moenkhausii, an abundant small
      sized characin fish with broad occurrence in the Parana River basin, Brazil.
      Specimens were collected monthly to determine fecundity, length at first
      maturity, reproductive period and spawning type. Gonads were macroscopically
      classified according to their form, size and texture in three different stages
      (immature, maturing or mature). Histological procedures were conducted to confirm
      gonadal developmental stages, and it was possible to notice that maturing females
      actually presented atretic oocytes, and all males that were macroscopically
      classified as immature, maturing and mature actually presented abundant
      spermatozoa in their gonads. Because of these discrepancies, a reclassification
      of gonadal maturations stages was needed after histological analysis, reinforcing
      its importance to studies on the reproduction of small characins. Reproduction
      occurred throughout the year though with two peaks. The length of the smallest
      mature individuals was 13 mm SL for males and 24 mm SL for females. Despite
      presenting relatively small batch fecundity, some life history traits such as
      early reproduction, multiple spawning throughout the year, in association with
      known opportunistic feeding habits, explain the high abundance of this species in
      locations where it occurs. 

PMID- 24661025
TI  - Drug carriers for the delivery of therapeutic peptides.
AB  - Peptides take on an increasingly important role as therapeutics in areas
      including diabetes, oncology, and metabolic, cardiovascular, and infectious
      diseases. In addition, many peptides such as insulin have been employed for many
      years. A challenge in the administration of peptide drugs is their often low
      hydrolytic stability, as well as other problems that are common to any drug
      treatment such as systemic distribution. There is a significant attention in the
      literature of protein drugs and their delivery strategies, but not many overviews
      are specifically dedicated to peptides. In this review, the different approaches
      to deliver peptides have been summarized where the focus is only on drug carriers
      based on organic materials. Initial discussion is on different methods of polymer
      peptide conjugation before being followed by physical encapsulation techniques,
      which is divided into surfactant-based techniques and polymer carriers.
      Surfactant-based techniques are dominated by liposome, microemulsions and solid
      lipid nanoparticles. The field widens further in the polymer field. The delivery
      of peptides has been enhanced using polymer-decorated liposomes, solid
      microspheres, polyelectrolyte complex, emulsions, hydrogels, and injectable
      polymers. The aim of this article is to give the reader an overview over the
      different types of carriers. 

PMID- 24661026
TI  - Domino asymmetric conjugate addition-conjugate addition.
AB  - Enantioenriched Al-, Mg-, and Zn-enolates undergo electrophilic trapping by
      nitroolefins and vinylsulfones to afford 1,4-diketones and 2
      (bis(phenylsulfonyl)ethyl)ketones in good yield and excellent
      diastereoselectivity. A one-pot preparation of indenes and enantiopure syntheses
      of tetrahydrobenzofurans, tetrahydrobenzopyrroles, and azulenes are disclosed. A
      site-selective two-step sequence of three conjugate additions is also
      demonstrated. 

PMID- 24661024
TI  - Cationic membrane-active peptides - anticancer and antifungal activity as well as
      penetration into human skin.
AB  - Cationic antimicrobial peptides are ancient natural broad-spectrum antibiotics,
      and several compounds also exhibit anticancer activity. However, most
      applications pertain to bacterial infections, and treatment for skin cancer is
      less frequently considered. The cytotoxicity of melittin, cecropin A, protegrin-1
      and histatin 5 against squamous skin cancer cell lines and normal human
      keratinocytes was evaluated and compared to established drugs. The results show
      that melittin clearly outperforms 5-fluorouracil regarding antitumor activity.
      Importantly, combined melittin and 5-fluorouracil enhanced cytotoxic effects on
      cancer cells and reduced toxicity on normal keratinocytes. Additionally, minimum
      inhibitory concentrations indicate that melittin also shows superior activity
      against clinical and laboratory strains of Candida albicans compared to
      amphotericin B. To evaluate its potential for topical applications, human skin
      penetration of melittin was investigated ex vivo and compared to two non-toxic
      cell-penetrating peptides (CPPs), low molecular weight protamine (LMWP) and
      penetratin. The stratum corneum prevents penetration into viable epidermis over 6
      h; however, the peptides gain access to the viable skin after 24 h. Inhibition of
      digestive enzymes during skin penetration significantly enhances the availability
      of intact peptide. In conclusion, melittin may represent an innovative agent for
      non-melanoma skin cancer and infectious skin diseases. In order to develop a drug
      candidate, skin absorption and proteolytic digestion by skin enzymes need to be
      addressed. 

PMID- 24661027
TI  - Fear, excitement, and financial risk-taking.
AB  - Can fear trigger risk-taking? In this paper, we assess whether fear can be
      reinterpreted as a state of excitement as a result of contextual cues and
      promote, rather than discourage, risk-taking. In a laboratory experiment, the
      participants' emotional states were induced (fear vs. control), followed by a
      purportedly unrelated financial task. The task was framed as either a stock
      market investment or an exciting casino game. Our results showed that incidental
      fear (vs. control) induced risk-averse behaviour when the task was framed as a
      stock investment decision. However, fear encouraged risk-taking when the very
      same task was framed as an exciting casino game. The impact of fear on risk
      taking was partially mediated by the excitement felt during the financial task. 

PMID- 24661028
TI  - An exploratory universal LC-MS/MS assay for bioanalysis of hinge region
      stabilized human IgG4 mAbs in clinical studies.
AB  - BACKGROUND: Due to the increasing number of monoclonal antibody (mAb) drug
      candidates entering clinical development, bioanalytical laboratories can benefit
      from generic liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays
      capable of quantifying a variety of human mAb-based therapeutic drug candidates
      in plasma/serum samples from clinical studies. RESULTS: We have developed and
      evaluated an exploratory LC-MS/MS assay capable of quantifying hinge region
      stabilized IgG4 therapeutic mAb drugs and drug candidates in clinical samples.
      The exploratory assay is based upon a single 'universal IgG4' surrogate peptide.
      CONCLUSION: The novel exploratory LC-MS/MS assay reported herein, upon further
      refinement and full validation, is predicted to enable bioanalytical scientists
      to quantify all hinge region-stabilized human IgG4 therapeutic mAbs in human
      studies without having to develop a new assay for every new stabilized IgG4 mAb
      entering clinical development.

PMID- 24661029
TI  - Injury perceptions, hope for recovery, and psychological status after spinal cord
      injury.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship of
      injury perceptions and hope for recovery with life satisfaction, purpose in life,
      and depressive symptoms measured during inpatient rehabilitation after spinal
      cord injury (SCI). METHOD: Participants included adults hospitalized for SCI
      inpatient rehabilitation (N = 208), each of whom completed a modified version of
      the Illness Perception Questionnaire and three outcome measures: the Purpose in
      Life Scale, the Satisfaction with Life Scale, and the abbreviated version of the
      Patient Health Questionnaire. RESULTS: Principal components analysis indicated an
      SCI perceptions factor regarding severity, permanence, and cure control of SCI,
      and a second factor related to hope for recovery. Whereas hope for recovery was
      nearly universal, injury perceptions were more varied. Favorable injury
      perceptions of SCI were predictive of purpose in life, whereas hope for recovery
      was predictive of life satisfaction. CONCLUSIONS: Hope for recovery and favorable
      SCI perceptions were related to positive psychological outcomes during inpatient
      rehabilitation, although the strength of the relationship was limited.

PMID- 24661031
TI  - A novel tri-allelic mutation of TMPRSS6 in iron-refractory iron deficiency
      anaemia with response to glucocorticoid.

PMID- 24661032
TI  - Posterior mitral leaflet left atrial anomalous chord in the absence of surgical
      mitral regurgitation.

PMID- 24661030
TI  - Comparing CESD-10, PHQ-9, and PROMIS depression instruments in individuals with
      multiple sclerosis.
AB  - PURPOSE: This study evaluated psychometric properties of the Patient Health
      Questionnaire-9 (PHQ-9), the Center for Epidemiological Studies Depression Scale
      10 (CESD-10), and the 8-item PROMIS Depression Short Form (PROMIS-D-8; 8b short
      form) in a sample of individuals living with multiple sclerosis (MS). RESEARCH
      METHOD: Data were collected by a self-reported mailed survey of a community
      sample of people living with MS (n = 455). Factor structure, interitem
      reliability, convergent/discriminant validity and assignment to categories of
      depression severity were examined. RESULTS: A 1-factor, confirmatory factor
      analytic model had adequate fit for all instruments. Scores on the depression
      scales were more highly correlated with one another than with scores on measures
      of pain, sleep disturbance, and fatigue. The CESD-10 categorized about 37% of
      participants as having significant depressive symptoms. At least moderate
      depression was indicated for 24% of participants by PHQ-9. PROMIS-D-8 identified
      19% of participants as having at least moderate depressive symptoms and about 7%
      having at least moderately severe depression. None of the examined scales had
      ceiling effects, but the PROMIS-D-8 had a floor effect. CONCLUSIONS: Overall,
      scores on all 3 scales demonstrated essential unidimensionality and had
      acceptable interitem reliability and convergent/discriminant validity.
      Researchers and clinicians can choose any of these scales to measure depressive
      symptoms in individuals living with MS. The PHQ-9 offers validated cutoff scores
      for diagnosing clinical depression. The PROMIS-D-8 measure minimizes the impact
      of somatic features on the assessment of depression and allows for flexible
      administration, including Computerize Adaptive Testing (CAT). The CESD-10
      measures 2 aspects of depression, depressed mood and lack of positive affect,
      while still providing an interpretable total score.

PMID- 24661037
TI  - A mortality event in wrasse species (Labridae) associated with the presence of
      viral haemorrhagic septicaemia virus.
AB  - Viral haemorrhagic septicaemia (VHS) is an infectious disease of farmed and wild
      fish and has an extensive host range in both freshwater and marine environments.
      In December 2012, a wrasse population consisting of ballan, Labrus bergylta
      (Ascanius), corkwing, Symphodus melops (L.), cuckoo, Labrus mixtus L., goldsinny,
      Ctenolabrus rupestris (L.), and rock cook, Centrolabrus exoletus (L.), held at a
      marine hatchery in the Shetland Isles, Scotland, experienced a mortality event.
      Approximately 10 000 wrasse were being held at the facility on behalf of an
      Atlantic salmon, Salmo salar L., aquaculture company prior to being deployed for
      the biological control of parasites on marine pen Atlantic salmon, aquaculture
      sites. Fish Health Inspectors from Marine Scotland Science initiated a diagnostic
      investigation, and subsequent diagnostic testing confirmed the site to be VHSV
      positive by qRT-PCR and virus isolation followed by ELISA. A VHSV genotype
      specific qRT-PCR assay revealed that the isolates belonged to genotype III, the
      European marine strain of the virus. The virus genotype was further confirmed by
      nucleic acid sequencing of the partial nucleoprotein (N) and glycoprotein (G)
      genes followed by BLAST nucleotide searches. This study reports for the first
      time the detection of VHSV within multiple wrasse species and highlights the need
      for a comprehensive risk-based approach to the use of wrasse and other finfish
      species as biological controls within the aquaculture industry. 

PMID- 24661038
TI  - Spectroscopic study on appearances of make-up skins using a visible RGB-LED OCT.
AB  - BACKGROUND/PURPOSE: Facial foundation is very effective to correct color
      irregularities of the skin surface and to protect the skin from harmful light.
      This depends strongly on both the optical properties and the coating condition of
      foundation on the skin surface. METHODS: We constructed the full-field optical
      coherence tomography (OCT) (FF-OCT) microscope with visible light sources of RGB
      LEDs. The commercially available skin replicas were used as the model of skin in
      the experiment, which were composed of two layers, a thin polyurethane film
      transcribed from cheek surface of a female and a beige-colored silicone
      substrate. The foundations were applied to the skin replicas under the constant
      pressure. RESULTS: A topographic image provides spectroscopic information of
      reflected light and effectiveness of correction of surface irregularities by
      applying the foundation. A tomographic image demonstrates the spectroscopic
      degree of light penetration into the skin tissue. It is shown that the
      reflectivity increases consistently with thickness of the applied foundation
      because light reflected from the surface and diffusively reflected from the
      inside of the tissue increases as the surface becomes flat applying the
      foundation. CONCLUSION: We confirmed experimentally the potential of the
      spectroscopic FF-OCT microscopy in investigating both qualitatively and
      quantitatively the effectiveness of facial foundation.

PMID- 24661039
TI  - Ectoparasitism and stress hormones: strategy of host exploitation, common host
      parasite history and energetics matter.
AB  - Parasites are thought to have numerous negative effects on their hosts. These
      negative effects may be associated with stress in a host. We evaluated the
      effects of four species of flea ectoparasites (Parapulex chephrenis, Synosternus
      cleopatrae, Xenopsylla conformis and Xenopsylla ramesis) on non-specific
      responses of eight species of rodents (Meriones crassus, Gerbillus dasyurus,
      Gerbillus andersoni, Gerbillus pyramidum, Gerbillus nanus, Acomys cahirinus,
      Acomys russatus and Mesocricetus auratus) and measured faecal glucocorticoid
      metabolites concentrations (FGMC) produced by the hosts. We found no effect of
      body mass of an individual rodent on FGMCs. Parasitism by fleas with a 'stay on
      the host body' exploitation strategy was associated with higher host FGMCs than
      parasitism by fleas that spent most of their life 'off-host'. FGMCs among rodents
      infested by the same flea species were correlated positively with the
      phylogenetic distance of a given rodent from the principal host of this flea;
      changes in FGMCs were lower in the host species more closely related to the
      flea's principal host. Changes in FMGCs of a host while parasitized were
      correlated with a host's change in body mass, where hosts that lost more body
      mass had higher FGMCs. Our results suggest that ectoparasitism can be stressful
      to their hosts. However, the occurrence of parasite-induced stress seems to
      depend on the identity of both host and parasite species and the evolutionary
      history of a host-parasite association. To our knowledge, this is the first
      multispecies study to evaluate the effect of ectoparasites on glucocorticoid
      hormones in small mammals. 

PMID- 24661040
TI  - The effect of weight reduction on treatment outcomes in obese patients with
      psoriasis on biologic therapy: a randomized controlled prospective trial.
AB  - BACKGROUND: Obesity has long been associated with psoriasis and it is considered
      to be an independent risk factor for chronic heart diseases in these patients.
      Recently, some of the biologic drugs used for psoriasis have been reported to
      cause increase in body weight. It is currently not clear if this increased body
      weight seen in psoriasis patients on biologics leads to decrease in there
      efficacy or vice versa. We carried out this study to see if reduction in body
      weight leads to increased efficacy of biologics in obese psoriasis patients.
      OBJECTIVE: To evaluate the effect of weight reduction by dietary control on
      treatment efficacy of biologics in obese patients as indicated by the Psoriasis
      Area and Severity Index (PASI) score. METHODS: Obese patients with psoriasis
      receiving biologic therapy, satisfying the inclusion criterion, were randomized
      in a 1:1 ratio to receive low-calorie diet versus normal diet (control group). We
      included 262 patients with moderate to severe, stable plaque psoriasis with a
      PASI score 20:50 on anti TNF-alpha biologic therapy (infliximab, etanercept,
      ustekinumab and adalimumab). The patients in the dietary intervention group were
      given a low calorie diet (<= 1000 kcal per day) for 8 weeks to induce weight
      loss. The treatment outcome was assessed using PASI. The PASI scores were
      assessed at baseline and every 4 weeks up to week 24. RESULTS: There were no
      significant differences in age, sex distribution, body weight, body mass index,
      waist circumference, psoriasis duration, or PASI score between the two studied
      groups at base line. At week 24, the mean (+/-SD) weight loss was 12.9 +/- 1.2 kg
      in the diet intervention group, and -1.5 +/- 0.5 kg in the control group. The
      average improvement in mean PASI score was 84% for the diet group, and 69% for
      the control group. PASI 75 was achieved by 85.9% in the diet group, and 59.3% in
      the control group (p < 0.001). The mean (+/-SD) body surface area values at week
      24 were 3.3 +/- 4.4% and 8.1 +/- 6.9% in the diet group and control group.
      CONCLUSIONS: Body weight reduction in obese patients on biologics may increase
      the efficacy of the drug.

PMID- 24661041
TI  - Nanodelivery systems for nucleic acid therapeutics in drug resistant tumors.
AB  - Development of intrinsic and acquired drug resistance in cancer is a significant
      clinical challenge for effective therapeutic outcomes. Multidrug resistance (MDR)
      in solid tumors is especially difficult to overcome due to the many different
      factors that influence clinically manifested refractory disease. Genetic
      profiling of MDR tumors can provide for more specific control through RNA
      interference (RNAi) therapy. However, there are multiple barriers to effective in
      vivo delivery of functional nucleic acid constructs, such as small interfering
      RNAs (siRNAs) and micro RNAs (miRNAs or miRs). In this review, we have briefly
      described the principles and mechanisms based on the RNA interference phenomenon
      and the barriers to its successful clinical translation. The principles of active
      and passive tumor targeting using nanoparticles systems are also discussed.
      Furthermore, illustrative examples of miRNA, siRNA, and gene-drug combination
      delivery using nanoparticle systems that have shown promising potentials for the
      treatment of diseases such as MDR cancers are covered. 

PMID- 24661042
TI  - Anderson-hynes pyeloplasty in patients less than 12 months old. Is the
      laparoscopic approach safe and feasible?
AB  - PURPOSE: The aim of our study is to compare the outcomes of open and laparoscopic
      pyeloplasty in children less than 12 months of age. PATIENTS AND METHODS: We
      reviewed all medical charts of patients less than 12 months old who underwent
      pyeloplasty from January 2007 to February 2013. We divided them in two groups:
      Open pyeloplasty (OP) and laparoscopic pyeloplasty (LP). The following data were
      analyzed: age, sex, weight, US measurements, operative time, hospital stay,
      complications, and success rate. Quantitative data were analyzed with the Student
      t test or Mann-Whitney U test, and chi-square test or Fisher test for qualitative
      data. RESULTS: Fifty-eight patients (46 boys and 12 girls) with a mean age of
      4.66 months (+/-3.05) were included. Mean age was 4.25 months and 5.15 months in
      OP and LP group respectively. Mean weight was 6.78 kg and 7.02 kg in OP and LP
      groups. There were no statistical differences in age, weight, and sex between OP
      and LP groups. There were no statistical differences in preoperative
      ultrasonography measurements. Mean posterior-anterior (PA) pelvis diameter was
      28.57 mm and 23.94 mm in OP and LP groups, respectively. Mean calices diameter
      were 10.86 mm and 10.96 mm in OP and LP groups, respectively. Mean operative time
      was 129.53 minutes in the OP group and 151.92 minutes in the LP group with
      statistical differences (P=0.018). Mean hospital stay was 6.34 days in the OP
      group and 3.46 in the LP group with statistical differences (P<0.05). No
      intraoperative and postoperative complications were found in either group.
      Hydronephrosis improved in all patients, and no patient needed a repeated
      pyeloplasty. CONCLUSION: The laparoscopic approach of Anderson-Hynes pyeloplasty
      in patients less than 12 months old is a safe procedure with the same outcomes as
      the open approach.

PMID- 24661043
TI  - Tandem oxidative processes catalyzed by polymer-incarcerated multimetallic
      nanoclusters with molecular oxygen.
AB  - Heterogeneous catalysis and one-pot tandem reactions are key for efficient and
      practical organic syntheses and for green and sustainable chemistry.
      Heterogeneous catalysts can be recovered and reused. These catalysts can be
      applied to efficient systems, such as continuous-flow systems. Tandem reactions
      often proceed via highly reactive but unstable intermediates. Tandem reactions do
      not require workup or much purification of the intermediate. This Account
      summarizes recent developments that we have made in the field of multifunctional
      heterogeneous metal nanocluster catalysts for use in tandem reactions based on
      aerobic oxidation reactions as key processes. We constructed our heterogeneous
      metal nanoclusters via two important procedures--microencapsulation and cross
      linking--using polystyrene-based copolymers with cross-linking moieties. These
      frameworks can efficiently stabilize small metal nanoclusters to maintain high
      catalytic activity without aggregation and leaching of nanoclusters. Aggregation
      and leaching are prevented by weak but multiple interactions between metal
      nanocluster surfaces and benzene rings in the copolymer as well as by the
      physical envelopment of cross-linked polymer backbones. Small nanoclusters,
      including multimetallic alloy clusters (nanoalloys), can be "imprisoned" into
      these cross-linked polymer composites. The term we use for these processes is
      polymer incarceration. Direct oxidative esterifications were achieved with
      polymer-incarcerated (PI) Au nanocluster catalysts. Amides were synthesized from
      alcohols and amines under aerobic oxidative conditions with PI bimetallic
      nanocluster catalysts composed of Au and Fe-group metals that formed separated
      nanoclusters rather than alloys. Oxidative lactam formation from amino alcohols
      was also achieved. On the other hand, imines could be prepared selectively from
      alcohols and amines with PI Au-Pd bimetallic nanoclusters. We also achieved the
      integration of the aerobic oxidation of allylic alcohols and the following
      Michael reaction catalyzed by trimetallic PI catalysts containing Au-Pd alloy
      nanoclusters and tetraalkoxyborates as cross-linkers. All of these heterogeneous
      catalysts could be recovered by simple operations and reused without significant
      loss of activity or any leaching of metals. We have demonstrated that the polymer
      incarceration method enables the simultaneous immobilization of several metals,
      with which we can achieve one-pot tandem oxidative processes using molecular
      oxygen as an oxidant within the multifunctional heterogeneous catalysts. Suitable
      choices of metals and bimetallic structures are crucial for the reactivity and
      the selection of reaction pathways.

PMID- 24661044
TI  - Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER)
      in first-relapse/primary refractory diffuse large B-cell lymphoma.
AB  - Relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is associated with a
      poor prognosis. Outcomes are particularly poor following immunochemotherapy
      failure or relapse within 12 months of induction. We conducted a Phase I/II trial
      of lenalidomide plus RICE (rituximab, ifosfamide, carboplatin, and etoposide)
      (RICER) as a salvage regimen for first-relapse or primary refractory DLBCL. Dose
      escalated lenalidomide was combined with RICE every 14 d. After three cycles of
      RICER, patients with chemosensitive disease underwent stem cell collection and
      consolidation with BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan]
      followed by autologous stem cell transplantation (autoSCT). Patients who
      recovered from autoSCT toxicities within 90 d initiated maintenance treatment
      with lenalidomide 25 mg daily for 21 d every 28 d for 12 months. No dose-limiting
      or unexpected toxicities occurred with lenalidomide 25 mg plus RICE. Grade 3/4
      haematological toxicities resolved appropriately, and planned dose density and
      dose intensity of RICER were preserved. No lenalidomide or RICE dose reductions
      were required in any of the three cycles. After two cycles of RICER, nine of 15
      patients (60%) achieved a complete response, and two achieved a partial response
      (13%). Combining lenalidomide with RICE is feasible, and results in promising
      response rates (particularly complete response rates) in high-risk DLBCL
      patients. 

PMID- 24661046
TI  - Experimental study of the competitive adsorption of HNO3 and H2O on surfaces by
      using Brewster angle cavity ring-down spectroscopy in the 295-345 nm region.
AB  - The competitive adsorption of HNO3 and H2O from the gas phase onto fused silica
      surfaces is investigated. Brewster angle cavity ring-down spectroscopy is used to
      measure absorption of a laser probe beam by the HNO3/H2O coadsorbed on fused
      silica surfaces as a function of the mixture pressure. The laser absorption
      measurements were made in the 295-345 nm region. Langmuir adsorption constants
      for nitric acid and water were found to be 107 +/- 17 and 562 +/- 21 Torr(-1),
      respectively. A method has been developed for calculating absorption by HNO3 and
      H2O codeposited on the surface as a function of the HNO3/H2O mixture pressure
      using multicomponent Langmuir adsorption isotherms and absorption cross-sections
      at a given wavelength for surface-adsorbed HNO3 and H2O. The validity of this
      treatment has been evaluated both as a function of wavelength and as a function
      of mixing ratio. 

PMID- 24661045
TI  - Metabolism of propyrisulfuron: 14C excretion, 14C concentration in plasma and
      tissues, and amount of metabolites in rats.
AB  - 1. Metabolism of a novel sulfonylurea herbicide, propyrisulfuron [1-(2-chloro-6
      propylimidazo[1,2-b]pyridazin-3-ylsulfonyl)-3-(4,6-dimethoxypyrimidin-2-yl)urea]
      labeled at the C-1 position of the propyl group and C-5 position of the
      pyrimidine ring with (14)C was investigated after a single oral administration in
      male and female rats. 2. Administered (14)C was excreted into the urine (5.7
      29.8%) and feces (64.6-97.4%), respectively. (14)C concentration in plasma
      reached a maximum level at 4 to 12 h post-administration and then decreased
      rapidly with a biological half-life of approximately 23 to 32 h. Total (14)C
      residues in the whole body were <0.1-1.4%, suggesting that the residues were not
      accumulated in the tissues. 3. The amount of metabolites in urine, feces, and
      bile were quantified using high-performance liquid chromatography (HPLC). There
      were no differences in metabolites found between male and female rats. 4. The
      absorption for the low dose (5 mg/kg) and the high dose (1000 mg/kg) was
      estimated to be approximately 90% and 20%, respectively, suggesting a saturable
      absorption. 5. The plasma protein binding in male and female rats was >= 98.8%,
      suggesting that propyrisulfuron had a strong affinity to plasma proteins.

PMID- 24661047
TI  - Prediction of globe rupture caused by primary blast: a finite element analysis.
AB  - Although a human eye comprises less than 0.1% of the frontal body surface area,
      injuries to the eye are found to be disproportionally common in survivors of
      explosions. This study aimed to introduce a Lagrangian-Eulerian coupling model to
      predict globe rupture resulting from primary blast effect. A finite element model
      of a human eye was created using Lagrangian mesh. An explosive and its
      surrounding air domain were modelled using Eulerian mesh. Coupling the two models
      allowed simulating the blast wave generation, propagation and interaction with
      the eye. The results showed that the peak overpressures caused by blast wave on
      the corneal apex are 2080, 932.1 and 487.3 kPa for the victim distances of 0.75,
      1.0 and 1.25 m, respectively. Higher stress occurred at the limbus, where the
      peaks for the three victim distances are 25.5, 14.1 and 6.4 MPa. The overpressure
      threshold of globe rupture was determined as 2000 kPa in a small-scale explosion.
      The findings would provide insights into the mechanism of primary blast-induced
      ocular injuries.

PMID- 24661048
TI  - Newly developed stepwise electroless deposition enables a remarkably facile
      synthesis of highly active and stable amorphous Pd nanoparticle electrocatalysts
      for oxygen reduction reaction.
AB  - This paper reports on highly active and stable amorphous Pd nanoparticle
      electrocatalysts for the oxygen reduction reaction. The amorphous catalysts were
      synthesized by a remarkably facile and quick electroless deposition process newly
      developed in this study (process time <5 min). An electrode substrate (glassy
      carbon, carbon cloth) was sequentially dipped for 10 s into two separate
      solutions of a reducing agent (sodium hypophosphite (NaH2PO2)) and Pd ions to
      deposit amorphous Pd nanoparticles containing phosphorus (Pd-P). By repeating the
      deposition cycles, the specific and mass activities of the Pd nanoparticles can
      be actively tuned. Owing to the nanoscale amorphous nature, the obtained Pd-P
      nanoparticle electrocatalysts exhibited superior specific and mass activities
      compared with crystalline Pd nanoparticles synthesized by another reducing agent
      (N2H4) and commercial Pt-loaded carbon (Pt/C) and Pd-loaded carbon (Pd/C). The
      specific and mass activities of the amorphous Pd-P nanoparticles were over 4.5
      times and 2.6 times higher than previously reported values of Pd and Pt
      catalysts. 

PMID- 24661049
TI  - Specialist hospital study shows that septic shock and drowsiness predict
      mortality in children under five with diarrhoea.
AB  - AIM: To evaluate the clinical characteristics and outcome in children
      hospitalised with diarrhoea, comparing those developed septic shock with those
      who did not. METHODS: We carried out a retrospective chart review on children
      aged 0-59 months admitted to the Dhaka Hospital, International Centre for
      Diarrhoeal Diseases Research, Bangladesh, with diarrhoea between October 2010 and
      September 2011. They were included if they had severe sepsis defined as
      tachycardia plus hyperthermia or hypothermia or an abnormal white blood cell
      count plus poor peripheral perfusion in absence of dehydration. Patients
      unresponsive to fluid and boluses, who required inotropes, were categorised as
      having septic shock (n = 88). The controls were those without septic shock (n =
      116). RESULTS: Death was significantly higher among the children with septic
      shock (67%) than the controls (14%) (p < 0.001). A logistic regression analysis,
      adjusted for potential confounders, found that children with septic shock were
      more likely to be drowsy on admission and received blood transfusions and
      mechanical ventilation (all p < 0.05). CONCLUSION: Children hospitalised for
      diarrhoea with septic shock were more likely to die, be drowsy on admission and
      receive blood transfusions and mechanical ventilation. A randomised clinical
      trial on inotropes in children with diarrhoea, severe sepsis and drowsiness may
      expedite their use and prevent mechanical ventilation and deaths.

PMID- 24661050
TI  - Left ventricular vortices as observed by vector flow mapping: main determinants
      and their relation to left ventricular filling.
AB  - BACKGROUND: Swirling flow, organized in vortices, contributes to adequate left
      ventricular function. In this study, we apply a novel echocardiographic flow
      mapping technique, vector flow mapping (VFM), to evaluate the main
      characteristics of left ventricular vortices and its relation to filling
      parameters. METHODS: Forty-eight subjects underwent conventional transthoracic
      echocardiographic examination with additional intracardiac flow assessment with
      VFM using a Aloka Alpha-10 system and experimental VFM analysis software. To
      analyze vortex behavior, its rotation direction, duration, location inside the
      left ventricle, size, and intensity were assessed in apical long-axis view. Its
      relation to conventional left ventricular filling parameters was then analyzed.
      RESULTS: Two vortex components were consistently identified following each
      transmitral filling wave. The anterior component of these visualized vortices was
      analyzed, due to its higher significance in the cardiac cycle, following early
      filling (V1) and atrial contraction (V2). Differences were observed in several
      aspects of vortex behavior between V1 and V2, particularly in patients with
      normal left ventricular filling parameters. These differences may be related to
      varying roles of vortices in different periods of the cardiac cycle. CONCLUSIONS:
      Vector flow mapping allowed visualization and measurement of several parameters
      defining vortex behavior inside the cardiac cycle. The differences observed in
      these parameters between vortices in different phases of the cardiac cycle may be
      related to their role in optimizing cardiac function.

PMID- 24661051
TI  - Scientific rigor and strategic vision are the key points for going forward in
      photomedicine.

PMID- 24661052
TI  - Guest molecule release triggers changes in the catalytic and magnetic properties
      of a Fe(II)-based 3D metal-organic framework.
AB  - A Fe(II)-based metal-organic framework (MOF), {[Fe2(pbt)2(H2O)2].2H2O}n,
      undergoes an irreversible dehydration, which triggers changes in the catalytic
      and magnetic properties of the MOF. These property changes are attributed to the
      high-spin to low-spin transition of 7.1% center Fe(II), which is demonstrated by
      (57)Fe Mossbauer, X-ray photoelectron spectroscopy, and UV/vis absorption
      spectra. 

PMID- 24661053
TI  - Palladium-catalyzed trifluoromethylthiolation of aryl C-H bonds.
AB  - A method for monotrifluoromethylthiolation of arenes via palladium-catalyzed
      directed C-H bond activation was described. The reaction was compatible with a
      variety of functional groups. Initial mechanistic studies disclosed that the
      turnover limiting step of the catalytic cycle did not involve C-H activation. 

PMID- 24661054
TI  - The role of object categories in hybrid visual and memory search.
AB  - In hybrid search, observers search for any of several possible targets in a
      visual display containing distracting items and, perhaps, a target. Wolfe (2012)
      found that response times (RTs) in such tasks increased linearly with increases
      in the number of items in the display. However, RT increased linearly with the
      log of the number of items in the memory set. In earlier work, all items in the
      memory set were unique instances (e.g., this apple in this pose). Typical real
      world tasks involve more broadly defined sets of stimuli (e.g., any "apple" or,
      perhaps, "fruit"). The present experiments show how sets or categories of targets
      are handled in joint visual and memory search. In Experiment 1, searching for a
      digit among letters was not like searching for targets from a 10-item memory set,
      though searching for targets from an N-item memory set of arbitrary alphanumeric
      characters was like searching for targets from an N-item memory set of arbitrary
      objects. In Experiment 2, observers searched for any instance of N sets or
      categories held in memory. This hybrid search was harder than search for specific
      objects. However, memory search remained logarithmic. Experiment 3 illustrates
      the interaction of visual guidance and memory search when a subset of visual
      stimuli are drawn from a target category. Furthermore, we outline a conceptual
      model, supported by our results, defining the core components that would be
      necessary to support such categorical hybrid searches.

PMID- 24661055
TI  - Reducing implicit racial preferences: I. A comparative investigation of 17
      interventions.
AB  - Many methods for reducing implicit prejudice have been identified, but little is
      known about their relative effectiveness. We held a research contest to
      experimentally compare interventions for reducing the expression of implicit
      racial prejudice. Teams submitted 17 interventions that were tested an average of
      3.70 times each in 4 studies (total N = 17,021), with rules for revising
      interventions between studies. Eight of 17 interventions were effective at
      reducing implicit preferences for Whites compared with Blacks, particularly ones
      that provided experience with counterstereotypical exemplars, used evaluative
      conditioning methods, and provided strategies to override biases. The other 9
      interventions were ineffective, particularly ones that engaged participants with
      others' perspectives, asked participants to consider egalitarian values, or
      induced a positive emotion. The most potent interventions were ones that invoked
      high self-involvement or linked Black people with positivity and White people
      with negativity. No intervention consistently reduced explicit racial
      preferences. Furthermore, intervention effectiveness only weakly extended to
      implicit preferences for Asians and Hispanics.

PMID- 24661056
TI  - Real-time image-processing algorithm for markerless tumour tracking using X-ray
      fluoroscopic imaging.
AB  - OBJECTIVE: To ensure accuracy in respiratory-gating treatment, X-ray fluoroscopic
      imaging is used to detect tumour position in real time. Detection accuracy is
      strongly dependent on image quality, particularly positional differences between
      the patient and treatment couch. We developed a new algorithm to improve the
      quality of images obtained in X-ray fluoroscopic imaging and report the
      preliminary results. METHODS: Two oblique X-ray fluoroscopic images were acquired
      using a dynamic flat panel detector (DFPD) for two patients with lung cancer. The
      weighting factor was applied to the DFPD image in respective columns, because
      most anatomical structures, as well as the treatment couch and port cover edge,
      were aligned in the superior-inferior direction when the patient lay on the
      treatment couch. The weighting factors for the respective columns were varied
      until the standard deviation of the pixel values within the image region was
      minimized. Once the weighting factors were calculated, the quality of the DFPD
      image was improved by applying the factors to multiframe images. RESULTS:
      Applying the image-processing algorithm produced substantial improvement in the
      quality of images, and the image contrast was increased. The treatment couch and
      irradiation port edge, which were not related to a patient's position, were
      removed. The average image-processing time was 1.1 ms, showing that this fast
      image processing can be applied to real-time tumour-tracking systems. CONCLUSION:
      These findings indicate that this image-processing algorithm improves the image
      quality in patients with lung cancer and successfully removes objects not related
      to the patient. ADVANCES IN KNOWLEDGE: Our image-processing algorithm might be
      useful in improving gated-treatment accuracy.

PMID- 24661057
TI  - Clinical manifestations of pancreas disease outbreaks in Norwegian marine salmon
      farming - variations due to salmonid alphavirus subtype.
AB  - Pancreas disease (PD) in Norwegian salmonid aquaculture has traditionally been
      caused by salmonid alphavirus (SAV) subtype 3. Following the isolation of a novel
      SAV subtype in 2010, marine SAV2, two separate endemic areas have developed. It
      has been debated whether disease outbreaks due to marine SAV2 result in milder
      clinical manifestations compared to outbreaks caused by SAV3. The aim of this
      study was to descriptively investigate site-level differences in the clinical
      manifestations of marine SAV2 and SAV3 at Norwegian seawater sites diagnosed with
      PD in 2012. The findings suggest that Norwegian PD outbreaks caused by marine
      SAV2 result in lower mortality and milder clinical signs compared to outbreaks
      caused by SAV3. For sites without reported PD-related mortality, there was no
      difference in the mortality levels between sites infected by marine SAV2 and
      SAV3. The results also indicate that there are no differences in grading quality
      at slaughter between the SAV subtypes. 

PMID- 24661059
TI  - Brain proteomics identifies potential simvastatin targets in acute phase of
      stroke in a rat embolic model.
AB  - Finding an efficient neuroprotectant is of urgent need in the field of stroke
      research. The goal of this study was to test the effect of acute simvastatin
      administration after stroke in a rat embolic model and to explore its mechanism
      of action through brain proteomics. To that end, male Wistar rats were subjected
      to a Middle Cerebral Arteria Occlusion and simvastatin (20 mg/kg s.c) (n = 11) or
      vehicle (n = 9) were administered 15 min after. To evaluate the neuroprotective
      mechanisms of simvastatin, brain homogenates after 48 h were analyzed by two
      dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology. We
      confirmed that simvastatin reduced the infarct volume and improved neurological
      impairment at 48 h after the stroke in this model. Considering our proteomics
      analysis, 66 spots, which revealed significant differences between groups, were
      analyzed by matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry allowing the identification of 27 proteins. From these results, we
      suggest that simvastatin protective effect can be partly explained by the
      attenuation of the oxidative and stress response at blood-brain barrier level
      after cerebral ischemia. Interestingly, analyzing one of the proteins (HSP75) in
      plasma from stroke patients who had received simvastatin during the acute phase,
      we confirmed the results found in the pre-clinical model. Our aim was to study
      statins benefits when administered during the acute phase of stroke and to
      explore its mechanisms of action through brain proteomics assay. Using an embolic
      model, simvastatin-treated rats showed significant infarct volume reduction and
      neurological improvement compared to vehicle-treated group. Analyzing their
      homogenated brains by two-dimensional fluorescence Difference in Gel
      Electrophoresis (DIGE) technology, we concluded that the protective effect of
      simvastatin can be attributable to oxidative stress response attenuation and
      blood-brain barrier protection after cerebral ischemia. 

PMID- 24661060
TI  - Induced cell death pathway post photodynamic therapy using a
      metallophthalocyanine photosensitizer in breast cancer cells.
AB  - OBJECTIVE: Zinc phthalocyanine (ZnPcSmix) was used as the photosensitizer (PS) in
      this study to investigate the cell death patterns as a result of photodynamic
      therapy (PDT) in a breast cancer cell line (MCF-7) in vitro using a 680 nm diode
      laser at a fluence of 5 J/cm(2). BACKGROUND: PDT is a noninvasive form of cancer
      therapy, successfully applied for the treatment of various cancer types. METHODS:
      Flow cytometry using Annexin V-fluorescein isothiocyanate (FITC), a cell death
      immunosorbent assay (ELISA), and gene expression analysis following ZnPcSmix
      mediated PDT were performed to determine the induced cell death pathways.
      RESULTS: The apoptotic cells abounded after the treatment, nuclear fragmentation
      was seen as oligonucleosomal degradation and increased expression of the B-cell
      lymphoma 2 (Bcl-2), DNA fragmentation factor alpha (DFFA1), and caspase 2 (CASP2)
      genes, indicated that apoptosis is the main induced mode of cell death.
      CONCLUSIONS: ZnPcSmix mediated PDT led to an apoptotic cell death pathway and the
      PS used showed its ability to stimulate and initiate programmed cell death.

PMID- 24661061
TI  - Mercury oxidation via chlorine, bromine, and iodine under atmospheric conditions:
      thermochemistry and kinetics.
AB  - Emissions of gaseous mercury from combustion sources are the major source of Hg
      in the atmosphere and in environmental waters and soils. Reactions of Hg(o)(g)
      with halogens are of interest because they relate to mercury and ozone depletion
      events in the Antarctic and Arctic early spring ozone hole events, and the
      formation of Hg-halides (HgX2) is a method for removal of mercury from power
      generation systems. Thermochemistry and kinetics from published theoretical and
      experimental studies in the literature and from computational chemistry are
      utilized to compile a mechanism of the reactions considered as contributors to
      the formation of HgX2 (X = Cl, Br, I) to understand the reaction paths and
      mechanisms under atmospheric conditions. Elementary reaction mechanisms are
      assembled and evaluated using thermochemistry for all species and microscopic
      reversibility for all reactions. Temperature and pressure dependence is
      determined with quantum Rice Ramsperger Kassel (RRK) analysis for k(E) and master
      equation analysis for fall-off. We find that reactions of mercury with a small
      fraction of the reactor surface or initiation by low concentrations of halogen
      atoms is needed to explain the experimental conversion of Hg to HgX2 in the gas
      phase. The models do not replicate data from experiments that do not explicitly
      provide an atom source. The Hg insertion reaction into X2 (Hg + X2 -> HgX2) that
      has been reported is further studied, and we find agreement with studies that
      report high barriers. The high barriers prevent this insertion path from
      explaining the experimental data on HgX2 formation and Hg conversion under
      atmospheric conditions. Mechanism studies with low initial concentrations of
      halogen radicals show significant conversion of Hg under the experimental
      conditions. 

PMID- 24661062
TI  - Editorial: building global science capacity in child psychology and psychiatry -
      between the etic and emic of cross-cultural enquiry.

PMID- 24661063
TI  - Commentary: self-harm: a global health priority - reflections on Brunner et al.
      (2014).

PMID- 24661064
TI  - Optimized parametric skin modelling for diagnosis of skin abnormalities by
      combining light back-scatter and laser speckle imaging.
AB  - BACKGROUND/PURPOSE: Optical and parametric skin imaging methods which can
      efficiently identify invisible sub-skin features or subtle changes in skin layers
      are very important for accurate optical skin modelling. In this study, a hybrid
      method is introduced that helps develop a parametric optical skin model by
      utilizing interdisciplinary techniques including light back-scatter analysis,
      laser speckle imaging, image-texture analysis and Bayesian inference methods. The
      model aims to detect subtle skin changes and hence very early signs of skin
      abnormalities/diseases. METHODS: Light back-scatter and laser speckle image
      textural analysis are applied onto the normal and abnormal skin regions (lesions)
      to generate set of attributes/parameters. These are then optimized by Bayesian
      inference method in order to build an optimized parametric model. RESULTS: The
      attributes selected by Bayesian inference method in the optimization stage were
      used to build an optimized model and then successfully verified. It was clearly
      proven that Bayesian inference based optimization process yields good results to
      build an optimized skin model. CONCLUSION: The outcome of this study clearly
      shows the applicability of this hybrid method in the analysis of skin features
      and is therefore expected to lead development of non-invasive and low-cost
      instrument for early detection of skin changes.

PMID- 24661065
TI  - High methane storage capacity in aluminum metal-organic frameworks.
AB  - The use of porous materials to store natural gas in vehicles requires large
      amounts of methane per unit of volume. Here we report the synthesis, crystal
      structure and methane adsorption properties of two new aluminum metal-organic
      frameworks, MOF-519 and MOF-520. Both materials exhibit permanent porosity and
      high methane volumetric storage capacity: MOF-519 has a volumetric capacity of
      200 and 279 cm(3) cm(-3) at 298 K and 35 and 80 bar, respectively, and MOF-520
      has a volumetric capacity of 162 and 231 cm(3) cm(-3) under the same conditions.
      Furthermore, MOF-519 exhibits an exceptional working capacity, being able to
      deliver a large amount of methane at pressures between 5 and 35 bar, 151 cm(3)
      cm(-3), and between 5 and 80 bar, 230 cm(3) cm(-3). 

PMID- 24661066
TI  - Location-specific effects of attention during visual short-term memory
      maintenance.
AB  - Recent neuroimaging studies suggest that early sensory areas such as area V1 are
      recruited to actively maintain a selected feature of the item held in visual
      short-term memory (VSTM). These findings raise the possibility that visual
      attention operates in similar manners across perceptual and memory
      representations to a certain extent, despite memory-level and perception-level
      selections are functionally dissociable. If VSTM operates by retaining
      "reasonable copies" of scenes constructed during sensory processing (Serences et
      al., 2009, p. 207, the sensory recruitment hypothesis), then it is possible that
      selective attention can be guided by both exogenous (peripheral) and endogenous
      (central) cues during VSTM maintenance. Yet, the results from the previous
      studies that examined this issue are inconsistent. In the present study, we
      investigated whether attention can be directed to a specific item's location
      represented in VSTM with the exogenous cue in a well-controlled setting. The
      results from the four experiments suggest that, as observed with the endogenous
      cue, the exogenous cue can efficiently guide selective attention during VSTM
      maintenance. The finding is not only consistent with the sensory recruitment
      hypothesis but also validates the legitimacy of the exogenous cue use in past and
      future studies.

PMID- 24661067
TI  - Anchoring in action: manual estimates of slant are powerfully biased toward
      initial hand orientation and are correlated with verbal report.
AB  - People verbally overestimate hill slant by approximately 15 degrees  to 25
      degrees , whereas manual estimates (e.g., palm board measures) are thought to be
      more accurate. The relative accuracy of palm boards has contributed to the widely
      cited theoretical claim that they tap into an accurate, but unconscious, motor
      representation of locomotor space. In the current work, 4 replications (total N =
      204) carried out by 2 different laboratories tested an alternative anchoring
      hypothesis that manual action measures give low estimates because they are always
      initiated from horizontal. The results of all 4 replications indicate that the
      bias from response anchoring can entirely account for the difference between
      manual and verbal estimates. Moreover, consistent correlations between manual and
      verbal estimates given by the same observers support the conclusion that both
      measures are based on the same visual representation. Concepts from the study of
      judgment under uncertainty apply even to action measures in information rich
      environments.

PMID- 24661068
TI  - Efficacy and safety profile of evolocumab (AMG145), an injectable inhibitor of
      the proprotein convertase subtilisin/kexin type 9: the available clinical
      evidence.
AB  - INTRODUCTION: Despite the proven efficacy of statins, they are often reported to
      be inadequate to achieve low-density lipoprotein cholesterol (LDL-C) goals
      (especially in high-risk patients). Moreover, a large number of subjects cannot
      tolerate statins or full doses of these drugs. Thus, there is a need for
      additional effective LDL-C reducing agents. AREAS COVERED: Evolocumab (AMG145) is
      a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type
      9 that binds to the liver LDL receptor and prevents it from normal recycling by
      targeting it for degradation. Phase I and II trials revealed that its
      subcutaneous injection, either alone or in combination with statins, is able to
      reduce LDL-C from 40 to 80%, apolipoprotein B100 from 30 to 59% and
      lipoprotein(a) from 18 to 36% in a dose-dependent manner. The incidence of side
      effects seems to be low and mainly limited to nasopharyngitis, injection site
      pain, arthralgia and back pain. EXPERT OPINION: Evolocumab is an innovative
      powerful lipid-lowering drug, additive to statins and with an apparently large
      therapeutic range associated to a low rate of mild adverse events. If available
      data will be confirmed in long-term trials with strong outcomes, Evolocumab will
      provide an essential tool to treat high-risk patients who need to reach ambitious
      LDL-C target.

PMID- 24661069
TI  - Characterization of two groups of Pasteurella skyensis isolates from Atlantic
      salmon, Salmo salar L., based on serotype and 16S rRNA and rpoB gene partial
      sequences.

PMID- 24661070
TI  - High internal phase emulsion templating with self-emulsifying and
      thermoresponsive chitosan-graft-PNIPAM-graft-oligoproline.
AB  - High internal phase emulsion (HIPE)-templating is an attractive method of
      producing high porosity polymer foams with tailored pore structure, pore size and
      porosity. However, this method typically requires the use of large amounts of
      surfactants to stabilize the immiscible liquid phases, and polymerizable
      monomers/cross-linker in the continuous minority phase to solidify the HIPE,
      which may not be desirable in many applications. We show that polyHIPEs with a
      porosity of 73% can be formed solely using a copolymer of chitosan-graft-PNIPAM
      graft-oligoproline (CSN-PRO), which acts simultaneously as emulsifier and
      thermoresponsive gelator, and forms upon removal of the liquid templating phases,
      the bulk structure of the resulting polyHIPE. With only a small amount of
      surfactant (1%v/v in the aqueous phase), and varying the polymer concentration
      and internal phase volume ratio, different polyHIPEs with porosities of up to
      99%, surface areas in excess of 300 m(2)/g and controlled pore interconnectivity
      can be formed. The poly(CSN-PRO)HIPEs are also shown to be thermoresponsive and
      remained intact when immersed into water above 34  degrees C but dissolve below
      their LCST, which is useful for applications such as drug delivery and tissue
      engineering scaffolds. 

PMID- 24661071
TI  - Poor outcome prediction by burst suppression ratio in adults with post-anoxic
      coma without hypothermia.
AB  - PURPOSE: Burst suppression ratio (BSR) is a quantitative electroencephalography
      (qEEG) parameter. The purpose of our study was to compare the accuracy of BSR
      when compared to other EEG parameters in predicting poor outcomes in adults who
      sustained post-anoxic coma while not being subjected to therapeutic hypothermia.
      METHODS: EEG was registered and recorded at least once within 7 days of post
      anoxic coma onset. Electrodes were placed according to the international 10-20
      system, using a 16-channel layout. Each EEG expert scored raw EEG using a grading
      scale adapted from Young and scored amplitude-integrated electroencephalography
      tracings, in addition to obtaining qEEG parameters defined as BSR with a defined
      threshold. Glasgow outcome scales of 1 and 2 at 3 months, determined by two
      blinded neurologists, were defined as poor outcome. RESULTS: Sixty patients with
      Glasgow coma scale score of 8 or less after anoxic accident were included. The
      sensitivity (97.1%), specificity (73.3%), positive predictive value (82.5%), and
      negative prediction value (95.0%) of BSR in predicting poor outcome were higher
      than other EEG variables. BSR1 and BSR2 were reliable in predicting death (area
      under the curve > 0.8, P < 0.05), with the respective cutoff points being 39.8%
      and 61.6%. BSR1 was reliable in predicting poor outcome (area under the curve  = 
      0.820, P < 0.05) with a cutoff point of 23.9%. BSR1 was also an independent
      predictor of increased risk of death (odds ratio  =  1.042, 95% confidence
      intervals: 1.012-1.073, P  =  0.006). DISCUSSION: BSR may be a better predictor
      in prognosticating poor outcomes in patients with post-anoxic coma who do not
      undergo therapeutic hypothermia when compared to other qEEG parameters.

PMID- 24661072
TI  - Thrombolysis and reperfusion: advanced understanding of early management
      strategies in acute ischemic stroke.
AB  - Currently, intravenous (IV) thrombolysis within 3 hours from stroke onset is the
      only approved treatment in acute ischemic stroke (AIS). Although effective, the
      definition of therapeutic time window and appropriate patient selection still
      remains controversial. Notably, early endovascular treatment strategies may serve
      as an adjunct therapy for time window extension in AIS. In this article, we
      review the safety and efficacy of IV thrombolysis in AIS as it pertains to the
      optimal time window, the selection of eligible patients, and in combination with
      endovascular treatment. Combined clinical application of IV thrombolysis and
      endovascular therapy may improve the therapeutic outcomes for AIS patients. 

PMID- 24661073
TI  - Testicular lesions and epididymal sperm parameters in the Iranian river buffalo
      (Bubalus bubalis).
AB  - The aim of this study was to evaluate the testicular lesions and their effects on
      the epididymal sperm parameters in the Iranian river buffalo (Bubalus bubalis).
      Total numbers of 117 scrota from the pubertal buffalo were provided from the
      local slaughterhouse. The samples were evaluated for morphological parameters and
      any macro- or microscopic lesions. The sterile swabs from the testis parenchyma
      were subjected to microbiology culture. The epididymal spermatozoon was analysed
      for concentration, progressive motility and abnormalities. The results showed
      34.2% fibrotic adhesions between parietal and visceral layers of tunica vaginalis
      that was significantly different among seasons (P < 0.05). The cases of
      unilateral cryptorchidism and bilateral Sertoli cell tumour were detected, with
      no spermatozoa in the respected epididymides. Microscopic examination showed
      13.25% (31/234) lesions including general (51.61%; 16/31) and multifocal (29.03%;
      9/31) degenerations as well as interstitial orchitis (9.68%; 3/31) and the
      Sertoli cell tumour (6.45%; 2/31). No relationship between the lesions and the
      bacterial isolation (n = 6) was detected. The sperm parameters and morphological
      parameters of the testis were under influence of microscopic lesions (P < 0.05).
      In conclusion, the testicular macro- and microscopic lesions may have a
      noticeable contribution in the Iranian buffalo fertility. 

PMID- 24661074
TI  - Role of three-dimensional echocardiography in structural complications after
      acute myocardial infarction.
AB  - Three-dimensional echocardiography (3DE) is a unique cardiovascular imaging
      modality in terms of: ability to provide realistic anatomical views of cardiac
      structures in the beating heart and possibility to visualize cardiac structures
      from any desired perspective. Therefore, 3DE is emerging as an accurate imaging
      modality for a prompt diagnosis and detailed anatomical description of structural
      complications (SC) of acute myocardial infarction (AMI). We report 3 emblematic
      cases which show how both the transthoracic (TTE) and transesophageal (TEE) 3D
      imaging can provide precise anatomic information useful to address management of
      SC in AMI patients: (1) detailed assessment of size, location, and morphology of
      an apical ventricular septal defect (VSD) obtained with 3DTTE was pivotal in
      referring the patient to percutaneous closure of it; (2) size and location of a
      complex inferior VSD with irregular margins advised against percutaneous closure;
      and (3) 3DTEE assisted surgeons to choose between reparative or replacement
      surgery for an acute mitral regurgitation due to complete papillary muscle
      rupture. 

PMID- 24661075
TI  - Donor-derived myelodysplastic syndrome and acute leukaemia after allogeneic
      haematopoietic stem cell transplantation: incidence, natural history and
      treatment response.
AB  - Donor-derived myelodysplastic syndrome/acute leukaemia (DD-MDS/AL) is a rare life
      threatening complication of allogeneic haematopoietic stem cell (HSC)
      transplantation. However, it is unknown whether the risk differs by HSC source.
      Therefore, we evaluated the incidence of DD-MDS/AL in 2390 engrafted patients.
      With a median follow-up of 7.1 years (1-20.8), the incidence of DD-MDS/AL was
      0.53% (95% confidence interval (CI), 0.01-1.41%], 0.56% (95%CI, 0.01-1.36%) and
      0.56% (95%CI, 0.01-1.10%) in recipients of bone marrow (n = 1117), peripheral
      blood (n = 489) and umbilical cord blood (UCB, n = 784), respectively. While
      follow-up is shorter in recipients of UCB and peripheral blood, incidence of DD
      MDS/AL is, thus far, similar between HSC sources. 

PMID- 24661076
TI  - The unfortunate fetus: discourses of reproductive misfortune.

PMID- 24661077
TI  - Luminescent heteroleptic tris(dipyrrinato)indium(III) complexes.
AB  - To provide an improvement over the low fluorescence efficiencies often shown by
      homoleptic tris(dipyrrinato)indium(III) complexes, luminescent heteroleptic
      tris(dipyrrinato)indium(III) complexes bearing two types of dipyrrinato ligands
      are designed here by theoretical calculation and then synthesized. They possess
      frontier orbitals linked to suppression of the nonemissive charge-separated
      states; one shows a high fluorescence quantum yield (0.41) in toluene, which
      exceeds that of the corresponding BF2 complex. 

PMID- 24661078
TI  - Prokaryotic taxonomic and metabolic diversity of an intermediate salinity
      hypersaline habitat assessed by metagenomics.
AB  - A metagenome was obtained by pyrosequencing the total prokaryotic DNA from the
      water of a pond with intermediate salinity (13% salts) from a saltern located in
      Santa Pola, Spain. We analyzed and compared the phylogenomic and metabolic
      diversity of this saltern pond with respect to other two metagenomes obtained
      previously from the same saltern (ponds with 19% and 37% salts, respectively) and
      two reference metagenomes from marine and coastal lagoon habitats. A large
      microbial diversity, representing seven major higher taxa (Euryarchaeota,
      Gammaproteobacteria, Alphaproteobacteria, Actinobacteria, Bacteroidetes,
      Verrucomicrobia and Betaproteobacteria), was found. However, most sequences (57%)
      were not assigned to any previously described genus. Principal component analysis
      of tetranucleotide frequencies of assembled contigs showed the presence of new
      groups of Euryarchaeota, different from those previously described but related to
      Haloquadratum walsbyi and other members of the Halobacteriaceae. Besides, some
      new Gammaproteobacteria, several closely related to the recently isolated
      bacterium 'Spiribacter salinus' were observed. Metabolically, the nitrogen and
      carbon cycles appear to be very simplified in this extreme habitat. Light is
      extensively used as energy source by bacteriorhodopsins and other rhodopsins.
      Microorganisms known to use the 'salt-in' strategy are probably able to combine
      the accumulation of potassium ions and of compatible solutes. 

PMID- 24661080
TI  - Kinetic resolution of 2-substituted 2,3-dihydro-4-pyridones by palladium
      catalyzed asymmetric allylic alkylation: catalytic asymmetric total synthesis of
      indolizidine (-)-209I.
AB  - The kinetic resolution of 2-substituted-2,3-dihydro-4-pyridones was realized via
      a Pd-catalyzed allylic substitution reaction using a commercially available (S)-P
      Phos as a ligand, affording optically active dihydropyridones and C-allylated
      dihydropyridones in high yields and good enantioselectivities with the S-factor
      up to 43. With this protocol, a catalytic asymmetric total synthesis of
      indolizidine (-)-209I was realized for the first time. 

PMID- 24661079
TI  - Evidence for an angiotensin-(1-7) neuropeptidase expressed in the brain medulla
      and CSF of sheep.
AB  - Angiotensin-(1-7) [Ang-(1-7)] is an alternative product of the brain renin
      angiotensin system that exhibits central actions to lower blood pressure and
      improve baroreflex sensitivity. We previously identified a peptidase that
      metabolizes Ang-(1-7) to the inactive metabolite product Ang-(1-4) in CSF of
      adult sheep. This study purified the peptidase 1445-fold from sheep brain medulla
      and characterized this activity. The peptidase was sensitive to the chelating
      agents o-phenanthroline and EDTA, as well as the mercury compound p
      chloromercuribenzoic acid (PCMB). Selective inhibitors to angiotensin-converting
      enzyme, neprilysin, neurolysin, and thimet oligopeptidase did not attenuate
      activity; however, the metallopeptidase agent JMV-390 was a potent inhibitor of
      Ang-(1-7) hydrolysis (Ki = 0.8 nM). Kinetic studies using (125) I-labeled Ang-(1
      7), Ang II, and Ang I revealed comparable apparent Km values (2.6, 2.8, and 4.3
      MUM, respectively), but a higher apparent Vmax for Ang-(1-7) (72 vs. 30 and 6
      nmol/min/mg, respectively; p < 0.01). HPLC analysis of the activity confirmed the
      processing of unlabeled Ang-(1-7) to Ang-(1-4) by the peptidase, but revealed <
      5% hydrolysis of Ang II or Ang I, and no hydrolysis of neurotensin, bradykinin or
      apelin-13. The unique characteristics of the purified neuropeptidase may portend
      a novel pathway to influence actions of Ang-(1-7) within the brain. Angiotensin
      (1-7) actions are mediated by the AT7 /Mas receptor and include reduced blood
      pressure, decreased oxidative stress, enhanced baroreflex sensitivity, and
      increased nitric oxide (NO). Ang-(1-7) is directly formed from Ang I by
      neprilysin (NEP). We identify a new pathway for Ang-(1-7) metabolism in the brain
      distinct from angiotensin-converting enzyme-dependent hydrolysis. The Ang-(1-7)
      endopeptidase (A7-EP) degrades the peptide to Ang-(1-4) and may influence central
      Ang-(1-7) tone. 

PMID- 24661081
TI  - Treatment of diabetic macular edema with sustained-release glucocorticoids:
      intravitreal triamcinolone acetonide, dexamethasone implant, and fluocinolone
      acetonide implant.
AB  - INTRODUCTION: Diabetic macular edema (DME) can be treated with intravitreal
      glucocorticoids, particularly triamcinolone acetonide, dexamethasone (DEX), and
      fluocinolone acetonide (FA). AREAS COVERED: The pathophysiology of DME includes
      multiple growth factors such as VEGF and also inflammatory mediators.
      Glucocorticoids act on DME through multiple pathways, and current research into
      their efficacy, safety, and therapeutic potential when administered
      intravitreally is discussed. CONCLUSION: The intravitreal route of administration
      minimizes systemic side effects of glucocorticoids. Furthermore, sustained
      release low-dose delivery via the DEX implant or the FA implant will limit
      frequent intravitreal injection and possibly some cost associated with
      intravitreal anti-VEGF therapy. In addition, the durable action of these
      treatments facilitates combination therapy. Patients can receive these implants
      as foundational therapy, and then receive additional treatment with laser or
      intravitreal anti-VEGF agents as combination therapy, which may conceivably
      provide some synergistic benefit. While the FA implant lasts much longer than the
      DEX implant, potentially decreasing the visit and treatment burden on patients
      and their families, the FA implant appears to have a greater risk of inducing
      ocular hypertension and cataract. However, these modalities have not been
      directly compared in a clinical trial and there is insufficient evidence to draw
      more elaborate conclusions.

PMID- 24661082
TI  - Acidities of closo-1-COOH-1,7-C2B10H11 and amino acids based on icosahedral
      carbaboranes.
AB  - Carborane clusters are not found in Nature and are exclusively man-made. In this
      work we study, both experimentally and computationally, the gas-phase acidity
      (measured GA = 1325 kJ.mol(-1), computed GA = 1321 kJ.mol(-1)) and liquid-phase
      acidity (measured pKa = 2.00, computed pKa = 1.88) of the carborane acid closo-1
      COOH-1,7-C2B10H11. The experimental gas-phase acidity was determined with
      electrospray tandem mass spectrometry (ESI/MS), by using the extended Cooks
      kinetic method (EKM). Given the similar spatial requirements of the title
      icosahedral cage and benzene and the known importance of aminoacids as a whole,
      such a study is extended, within an acid-base context, to corresponding ortho,
      meta, and para amino acids derived from icosahedral carborane cages, 1-COOH-n-NH2
      1, n-R with {R = C2B10H10, n = 2, 7, 12}, and from benzene {R = C6H4, n = 2, 3,
      4}. A remarkable difference is found between the proportion of neutral versus
      zwitterion structures in water for glycine and the carborane derived amino acids.

PMID- 24661083
TI  - How to make choice of the carious removal methods, Carisolv or traditional
      drilling? A meta-analysis.
AB  - Despite Carisolv has been used to remove carious dentine for 14 years, it still
      has not reached consensus regarding its effectiveness and efficacy. We undertook
      a systematic review and meta-analysis of published randomised controlled trials
      (RCTs) to assess the effectiveness and efficacy of the chemomechanical caries
      removal (CMCR) system - Carisolv. A systematic electronic literature search was
      conducted to identify RCTs comparing the use of Carisolv with a control (rotary
      instruments) in patients with dental caries. Results were expressed as risk
      ratios (RRs) or mean differences with accompanying 95% confidence intervals
      (CIs). The outcome measurement included the complete caries removal rate (CCR:
      the number of cases with complete caries removal in study and control groups
      after different treatment), the treatment time (min) and the use of local
      anaesthesia. The meta-analysis was performed with the fixed-effect or random
      effect model according to the heterogeneity. Six studies involving 578 teeth met
      our inclusion criteria. There was no statistically significant difference in CCR
      between Carisolv group and rotary instruments group; in Carisolv group, the
      treatment time (min) was significantly longer no matter whether the caries was
      located in coronal or root area, while the use of local anaesthesia was less.
      Compared with rotary instruments, Carisolv did not show increased CCR. Carisolv
      reduced the use of local anaesthesia although it took longer treatment time.
      However, the results should be interpreted cautiously due to the heterogeneity
      among study designs. Further large-scale, well-designed RCTs are needed.

PMID- 24661084
TI  - Low-level laser therapy with 810 nm wavelength improves skin wound healing in
      rats with streptozotocin-induced diabetes.
AB  - OBJECTIVE: The aim of present study was to evaluate whether low-level laser
      therapy (LLLT) can reverse the impaired wound healing process in diabetic rats.
      BACKGROUND DATA: Impaired wound healing in diabetic patients represents a major
      health problem. Recent studies have indicated that LLLT may improve wound healing
      in diabetic rats, but the optimal treatment parameters are still unknown.
      MATERIALS AND METHODS: Male Sprague-Dawley rats (n=21) were randomly divided into
      three groups: a healthy control group, a diabetic sham-treated group, and a
      diabetic LLLT-treated group. Diabetes mellitus was then induced by streptozotocin
      administration to the two diabetic groups. One 4 cm long full thickness skin
      incision and one full thickness circular excision (diameter=4 mm) were performed
      on the back of each rat. An infrared 810 nm laser with an output of 30 mW, a
      power density of 30 mW/cm(2), and a spot size of 1 cm(2) was used to irradiate
      each wound for 30 sec (daily dose of 0.9 J/cm(2)/wound/day). RESULTS: In diabetic
      rats, the histology of LLLT-treated excisions revealed a similar healing response
      to that in nondiabetic controls, with significantly more mature granulation
      tissue than in the sham-treated diabetic control group. LLLT reduced the loss of
      tensile strength, and increased the incision wound stiffness significantly
      compared with sham-irradiated rats, but this did not achieve the same level as in
      the nondiabetic controls. CONCLUSIONS: Our study demonstrates that infrared LLLT
      can improve wound healing in diabetic rats. Nevertheless, further research needs
      to be performed to evaluate the exact underlying mechanism and to further
      optimize LLLT parameters for clinical use.

PMID- 24661085
TI  - Which measures of adiposity are related to Australian adolescent's perception of
      their weight?
AB  - AIM: To determine which measurement of adiposity - standardised body mass index
      (BMI-z), waist circumference or body fat percentage - is most closely correlated
      with adolescents' weight perception and whether this differs by gender. METHODS:
      Weight and height (used to calculate BMI-z), waist circumference and body fat
      percentage were measured in 2278 adolescents aged between 12 and 16 and compared
      with self-reported weight status. RESULTS: The distribution of subjects across
      the three weight categories (underweight, healthy weight and overweight) differed
      significantly between BMI-z, waist circumference and body fat percentage (p <
      0.001). BMI-z was most closely aligned with perceived weight status in boys and
      girls, and waist circumference was also a good correlate of weight perception in
      boys. Boys were more likely than girls to underestimate their weight when it was
      defined by BMI-z; however, girls were equally likely to underestimate their
      weight when it was defined by waist circumference. The majority of adolescents
      underestimated their weight status when it was defined by BF%. CONCLUSION: BMI-z
      is the closest correlate of self-perceived weight status. In the absence of
      internationally accepted reference values for waist circumference, BMI-z is the
      most appropriate measure to verify weight perception.

PMID- 24661086
TI  - Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of
      cancer.
AB  - INTRODUCTION: Chimeric antigen (or antibody) receptors (CAR) are fusion proteins
      typically combining an antibody-derived targeting fragment with signaling domains
      capable of activating immune cells. Recent clinical trials have shown the
      tremendous potential of adoptive cell transfer (ACT) of autologous T cells
      engineered to express a CD19-specific CAR targeting B-cell malignancies. Building
      on this approach, ACT therapies employing allogeneic CAR-expressing cytotoxic
      cells are now being explored. AREAS COVERED: The basic principles of CAR-ACT are
      introduced. The potential benefits as well as problems of using allogeneic CAR
      modified cells against tumor antigens are discussed. Various approaches to
      allogeneic CAR therapy are presented, including donor leukocyte infusion, CAR
      redirected gammadelta T cells and natural killer cells, strategies to avoid graft
      versus-host disease, modulation of lymphocyte migration, and exploitation of
      graft-versus-host reactivity. EXPERT OPINION: CAR-modified allogeneic cells have
      the potential to act as universal effector cells, which can be administered to
      any patient regardless of MHC type. Such universal effector cells could be used
      as an 'off-the-shelf' cell-mediated treatment for cancer.

PMID- 24661087
TI  - Dual fucci: a new transgenic line for studying the cell cycle from embryos to
      adults.

PMID- 24661088
TI  - Phenotypic abnormalities of peripheral blood mononuclear cells in patients with
      Behcet's disease and association with HLA-B51 expression.
AB  - The aim of this study was to investigate the subclasses and the immunophenotypic
      profile of peripheral mononuclear cells in patients with Behcet's disease (BD)
      and to assess associations between the expression of HLA-B51 antigen and that of
      other cell markers. Thirty healthy volunteer blood donors and forty patients with
      BD were enrolled into this study. Phenotyping was performed using two color flow
      cytometry. HLA-B51 typing was performed using the complement dependent
      microlymphocytotoxicity assay. Unlike controls, patients with BD presented a
      modified immunophenotypic profile of lymphocytes. Compared to those in the
      remission phase, patients with active BD showed an increased mean of MFI ratio of
      CD56 on CD16+CD56+ cells (32.47 +/- 14.26 versus 23.87 +/- 10.3; p = 0.032),
      increased absolute numbers of CD4(-)CD8(bright) and CD4(+)CD8(+) cells (657.1 +/-
      463.6 cells/uL versus 319.24 +/- 116.4 cells/uL; p = 0.017 and 40.77 +/- 36.41
      cells/uL versus 10.77 +/- 9.78 cells/uL; p < 0.0001, respectively) and an
      elevated mean of MFI ratio of CD19 on B cells (252.3 +/- 56.7 versus 205.67 +/-
      32.3; p = 0.021). However, expression of HLA-B51 was not associated with any
      specific immunophenotypic profile. In conclusion, abnormal immunophenotypic
      profile of peripheral lymphocytes was found in patients with BD, especially in
      active phase, reflecting an immune dysregulation. Moreover, HLA-B51 expression
      was not found to be related to the expression of other cell markers.

PMID- 24661090
TI  - New nanostructured zinc phosphite templated by cetyltrimethylammonium cations:
      synthesis, crystal structure, adsorption, and photoluminescence properties.
AB  - Nanostructured zinc phosphite templated by cetyltrimethylammonium (CTA(+))
      cations was synthesized using a hydro(solvo)thermal method. This is the first
      example of a crystalline metal phosphite containing long carbon tails of the
      CTA(+) ions as templates in its structure, as is structurally characterized by
      single-crystal X-ray diffraction. The 2D inorganic structures with 4.8(2)
      topologies are constructed from the interconnection of tetrahedral ZnO3Br and
      HPO3 units, which are sandwiched between CTA(+) ion surfactants in a packing
      behavior of a largely lamellar liquid-crystalline structure to extend the
      interlayer d spacing to 28.05 A. Adsorption experiment shows selective adsorption
      properties of 1-naphthol and a adsorption capacity of 0.17 mmol/mmol
      (CTA)ZnBr(HPO3). This compound has potential as an adsorbent for the removal of 1
      naphthol pollutant from wastewater. In addition, the naphthol-adsorbed sample
      shows interesting luminescent properties that are different from that of an as
      synthesized sample. The crystal structure, thermal stability, IR spectrum,
      adsorption, and photoluminescence properties have been studied. 

PMID- 24661089
TI  - Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is associated with poor
      outcome in childhood AML regardless of FLT3-ITD status: a report from the
      Children's Oncology Group.
AB  - Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a rare subtype associated
      with FLT3-internal tandem duplication (ITD) and poor outcomes. The clinical
      outcomes of paediatric patients with t(6;9) with and without FLT3-ITD treated on
      six consecutive cooperative trails were evaluated. In contrast to patients
      without t(6;9), those with t(6;9) had a significantly lower complete remission
      rate, higher relapse rate (RR), and poor overall survival (OS). Within t(6;9)
      patients, those with and without FLT3-ITD had an OS of 40% and 27% respectively
      (P > 0.9), demonstrating that t(6;9) is a high-risk cytogenetic feature in
      paediatric AML and its clinical impact is independent of the presence of FLT3
      ITD. 

PMID- 24661091
TI  - Pd(0)-catalyzed tandem deprotection/cyclization of tetrahydro-beta-carbolines on
      allenes: application to the synthesis of indolo[2,3-a]quinolizidines.
AB  - The pallado-catalyzed tandem deprotection/cyclization reaction of enantioenriched
      N-allyl tetrahydro-beta-carbolines on allenes is described. The first step
      generates in situ a deprotected tetrahydro-beta-carboline, which then undergoes a
      cyclization on the allene function via an intermediate pi-allyl Pd(II)
      derivative. This reaction results in the synthesis of various chiral indolic
      tetracycles (mainly indolo[2,3a]quinolizidine derivatives) presenting a vinyl
      function. 

PMID- 24661092
TI  - Is it okay to tell? Children's judgements about information disclosure.
AB  - The present research investigates how young children evaluate and reason about
      the disclosure of private information. Using story vignettes, children aged 4-5
      and 7-8 years were asked to evaluate an individual who passed on information from
      a peer revealing that he or she had broken a rule (e.g., stolen a cookie; rule
      type) or lacked a skill (e.g., could not ride a bicycle; competence type). These
      negative valence stories were compared with positive valence stories in which the
      peer had followed a rule or possessed a skill. Younger children approved the
      sharing of positive, but not negative, information, irrespective of type (rule
      vs. competence). Older children disapproved the disclosure of someone's
      incompetence, whereas they approved the disclosure of a rule violation. Children
      justified their evaluations by reference to social rules in the rule-type
      vignettes and to an individual's feelings in the competence-type vignettes. The
      findings suggest that young children are concerned about the disclosure of
      negative information about other people, but with age they become increasingly
      concerned about protecting the social order even at the cost of individual
      privacy.

PMID- 24661093
TI  - alpha6beta2*-subtype nicotinic acetylcholine receptors are more sensitive than
      alpha4beta2*-subtype receptors to regulation by chronic nicotine administration.
AB  - Nicotinic acetylcholine receptors (nAChR) of the alpha6beta2* subtype (where
      *indicates the possible presence of additional subunits) are prominently
      expressed on dopaminergic neurons. Because of this, their role in tobacco use and
      nicotine dependence has received much attention. Previous studies have
      demonstrated that alpha6beta2*-nAChR are down-regulated following chronic
      nicotine exposure (unlike other subtypes that have been investigated - most
      prominently alpha4beta2* nAChR). This study examines, for the first time, effects
      across a comprehensive chronic nicotine dose range. Chronic nicotine dose
      responses and quantitative ligand-binding autoradiography were used to define
      nicotine sensitivity of changes in alpha4beta2*-nAChR and alpha6beta2*-nAChR
      expression. alpha6beta2*-nAChR down-regulation by chronic nicotine exposure in
      dopaminergic and optic-tract nuclei was ~three-fold more sensitive than up
      regulation of alpha4beta2*-nAChR. In contrast, nAChR-mediated [(3) H]-dopamine
      release from dopamine-terminal region synaptosomal preparations changed only in
      response to chronic treatment with high nicotine doses, whereas dopaminergic
      parameters (transporter expression and activity, dopamine receptor expression)
      were largely unchanged. Functional measures in olfactory tubercle preparations
      were made for the first time; both nAChR expression levels and nAChR-mediated
      functional measures changed differently between striatum and olfactory tubercles.
      These results show that functional changes measured using synaptosomal [(3) H]-DA
      release are primarily owing to changes in nAChR, rather than in dopaminergic,
      function. This study examined dose-response relationships for murine alpha6beta2*
      nicotinic acetylcholine receptor (nAChR) down-regulation by chronic nicotine
      treatment. The ID50 value for alpha6beta2* down-regulation (35 nM) is ~ 3x lower
      than the ED50 value for alpha4beta2* nAChR up-regulation (95 nM), both well
      within the range reached by human smokers. Chronic nicotine treatment altered
      alpha6beta2*- and alpha4beta2*-nAChR-mediated [(3) H]-dopamine release from
      striatal and olfactory tubercle synaptosomes, but dopaminergic parameters were
      largely unaffected. We conclude that functional changes are primarily driven by
      altered nAChR activity. 

PMID- 24661094
TI  - CCL17 production by dendritic cells is required for NOD1-mediated exacerbation of
      allergic asthma.
AB  - RATIONALE: Pattern recognition receptors are attractive targets for vaccine
      adjuvants, and polymorphisms of the innate receptor NOD1 have been associated
      with allergic asthma. OBJECTIVES: To elucidate whether NOD1 agonist may favor
      allergic asthma in humans through activation of dendritic cells, and to evaluate
      the mechanisms involved using an in vivo model. METHODS: NOD1-primed dendritic
      cells from allergic and nonallergic donors were characterized in vitro on their
      phenotype, cytokine secretion, and Th2 polarizing ability. The in vivo relevance
      was examined in experimental allergic asthma, and the mechanisms were assessed
      using transfer of NOD1-conditioned dendritic cells from wild-type or CCL17
      deficient mice. MEASUREMENTS AND MAIN RESULTS: NOD1 priming of human dendritic
      cells promoted a Th2 polarization profile that involved the production of CCL17
      and CCL22 in nonallergic subjects but only CCL17 in allergic patients, without
      requiring allergen costimulation. Moreover, NOD1-primed dendritic cells from
      allergic donors exhibited enhanced maturation that led to abnormal CCL22 and IL
      10 secretion compared with nonallergic donors. In mice, systemic NOD1 ligation
      exacerbated allergen-induced experimental asthma by amplifying CCL17-mediated Th2
      responses in the lung. NOD1-mediated sensitization of purified murine dendritic
      cells enhanced production of CCL17 and CCL22, but not of thymic stromal
      lymphopoietin and IL-33, in vitro. Consistently, adoptive transfer of NOD1
      conditioned dendritic cells exacerbated the Th2 pulmonary response in a CCL17
      dependent manner in vivo. CONCLUSIONS: Data from this study unveil a deleterious
      role of NOD1 in allergic asthma through direct induction of CCL17 by dendritic
      cells, arguing for a need to address vaccine formulation safety issues related to
      allergy.

PMID- 24661095
TI  - Left ventricular restrictive filling pattern and the presence of contractile
      reserve in patients with low-flow/low-gradient severe aortic stenosis.
AB  - OBJECTIVE: We sought to study diastolic function in patients with low-flow/low
      gradient aortic stenosis (LF/LGAS) and to clarify the relationship between
      contractile reserve on dobutamine stress echocardiography (DSE) and the
      restrictive filling pattern on echocardiography in patients with LF/LGAS.
      PATIENTS AND METHODS: Thirty patients with LF/LG severe AS were divided into 2
      groups. Group I included 14 patients with contractile reserve on DSE. Group II
      included 16 patients with no contractile reserve on DSE. Diastolic function was
      studied in all patients using baseline echo Doppler study. RESULTS: No
      significant difference was found between both groups regarding baseline left
      ventriculae end-diastolic dimension (LVEDD), ejection fraction (EF), stroke
      volume, aortic valve area (AVA), mean transaortic pressure gradient, septal
      thickness or posterior wall thickness, P > 0.05. Transmitral E/A ratio was 1.3 +/
      0.5 compared to 2.6 +/- 0.7, respectively, deceleration time (DT) was 160 +/- 31
      compared to 120 +/- 15 ms, isovolumic relaxation time (IVRT) was 81 +/- 22
      compared to 53 +/- 18 ms, S/D ratio was 1.2 +/- 0.3 compared to 0.8 +/- 0.2,
      respectively, (P < 0.001 for all).Three patients in group I had restrictive
      pattern of diastolic dysfunction compared to 12 in group II (P < 0.003). DSE data
      in both groups showed a peak SV of 64 +/- 11 mL compared to 50 +/- 7 mL (P <
      0.005), peak EF was 42 +/- 9 compared to 34 +/- 11% (P < 0.03). Peak stress mean
      transaortic pressure gradient was 39 +/- 9 compared to 22 +/- 10 mmHg,
      respectively, P < 001. CONCLUSION: Restrictive filling pattern of diastolic
      dysfunction on baseline echo Doppler study may predict lack of contractile
      reserve in patients with LF/LG severe AS.

PMID- 24661097
TI  - Understanding boron through size-selected clusters: structure, chemical bonding,
      and fluxionality.
AB  - Boron is an interesting element with unusual polymorphism. While three
      dimensional (3D) structural motifs are prevalent in bulk boron, atomic boron
      clusters are found to have planar or quasi-planar structures, stabilized by
      localized two-center-two-electron (2c-2e) sigma bonds on the periphery and
      delocalized multicenter-two-electron (nc-2e) bonds in both sigma and pi
      frameworks. Electron delocalization is a result of boron's electron deficiency
      and leads to fluxional behavior, which has been observed in B13(+) and B19(-). A
      unique capability of the in-plane rotation of the inner atoms against the
      periphery of the cluster in a chosen direction by employing circularly polarized
      infrared radiation has been suggested. Such fluxional behaviors in boron clusters
      are interesting and have been proposed as molecular Wankel motors. The concepts
      of aromaticity and antiaromaticity have been extended beyond organic chemistry to
      planar boron clusters. The validity of these concepts in understanding the
      electronic structures of boron clusters is evident in the striking similarities
      of the pi-systems of planar boron clusters to those of polycyclic aromatic
      hydrocarbons, such as benzene, naphthalene, coronene, anthracene, or
      phenanthrene. Chemical bonding models developed for boron clusters not only
      allowed the rationalization of the stability of boron clusters but also lead to
      the design of novel metal-centered boron wheels with a record-setting planar
      coordination number of 10. The unprecedented highly coordinated borometallic
      molecular wheels provide insights into the interactions between transition metals
      and boron and expand the frontier of boron chemistry. Another interesting feature
      discovered through cluster studies is boron transmutation. Even though it is well
      known that B(-), formed by adding one electron to boron, is isoelectronic to
      carbon, cluster studies have considerably expanded the possibilities of new
      structures and new materials using the B(-)/C analogy. It is believed that the
      electronic transmutation concept will be effective and valuable in aiding the
      design of new boride materials with predictable properties. The study of boron
      clusters with intermediate properties between those of individual atoms and bulk
      solids has given rise to a unique opportunity to broaden the frontier of boron
      chemistry. Understanding boron clusters has spurred experimentalists and
      theoreticians to find new boron-based nanomaterials, such as boron fullerenes,
      nanotubes, two-dimensional boron, and new compounds containing boron clusters as
      building blocks. Here, a brief and timely overview is presented addressing the
      recent progress made on boron clusters and the approaches used in the authors'
      laboratories to determine the structure, stability, and chemical bonding of size
      selected boron clusters by joint photoelectron spectroscopy and theoretical
      studies. Specifically, key findings on all-boron hydrocarbon analogues, metal
      centered boron wheels, and electronic transmutation in boron clusters are
      summarized.

PMID- 24661098
TI  - A fully integrated isoprenoid emissions model coupling emissions to
      photosynthetic characteristics.
AB  - The lack of a mechanistic basis has hampered modelling isoprene emission
      responses to environmental drivers, in particular the simulation of isoprene
      emissions under different CO2 concentrations. Here, we advance previous semi
      mechanistic model formulations by introducing a model that explicitly links
      electron availability for other purpose than carbon assimilation (or available
      energy for secondary metabolism processes; supply-constraint) and enzyme activity
      (capacity-constraint) to emissions. We furthermore investigate the sensitivity of
      the model to variations in photosynthetic and emission-specific parameters. By
      comparing species-specific simulations with experimental data, we demonstrate
      that differences in photosynthetic characteristics can explain inter-species
      differences in emissions. Interestingly, the seasonal development of emissions
      could also be explained to some degree by the change in energy supply from
      photosynthesis throughout the season. In addition, we show that the principal
      responses are not limited to isoprene but can be formulated to describe the
      emission of other light-dependent volatile species. The proposed model is
      suitable for implementation into regional and global models, particularly those
      that already provide species-specific photosynthesis estimates.

PMID- 24661099
TI  - Mannitol infusion immediately after reperfusion suppresses the development of
      focal cortical infarction after temporary cerebral ischemia in gerbils.
AB  - Previously we found that, after temporary cerebral ischemia, microvasculogenic
      secondary focal cerebral cortical ischemia occurred, caused by microvascular
      obstruction due to compression by swollen astrocytic end-feet, resulting in focal
      infarction. Herein, we examined whether mannitol infusion immediately after
      restoration of blood flow could protect the cerebral cortex against the
      development of such an infarction. If so, the infusion of mannitol might improve
      the results of vascular reperfusion therapy. We selected stroke-positive animals
      during the first 10 min after left carotid occlusion performed twice with a 5-h
      interval, and allocated them into four groups: sham-operated control, no
      treatment, mannitol-infusion, and saline-infusion groups. Light- and electron
      microscopic studies were performed on cerebral cortices of coronal sections
      prepared at the chiasmatic level, where the focal infarction develops abruptly in
      the area where disseminated selective neuronal necrosis is maturing. Measurements
      were performed to determine the following: (A) infarct size in HE-stained
      specimens from all groups at 72 and 120 h after return of blood flow; (B) number
      of carbon-black-suspension-perfused microvessels in the control and at 0.5, 3, 5,
      8, 12 and 24 h in the no-treatment and mannitol-infusion groups; (C) area of
      astrocytic end-feet; and (D) number of mitochondria in the astrocytic end-feet in
      electron microscopic pictures taken at 5 h. The average decimal fraction area
      ratio of infarct size in the mannitol group was significantly reduced at 72 and
      120 h, associated with an increased decimal fraction number ratio of carbon-black
      suspension-perfused microvessels at 3, 5 and 8 h, and a marked reduction in the
      size of the end-feet at 5 h. Mannitol infusion performed immediately after
      restitution of blood flow following temporary cerebral ischemia remarkably
      reduced the size of the cerebral cortical focal infarction by decreasing the
      swelling of the end-feet, thus preventing the microvascular compression and
      stasis and thereby microvasculogenic secondary focal cerebral ischemia.

PMID- 24661101
TI  - Evaluation of oro-facial function in young subjects with temporomandibular
      disorders.
AB  - The aim of this study was to evaluate bite force (BF) and oro-facial functions at
      different dentition phases (initial-mixed, intermediate-mixed, final-mixed and
      permanent dentition) in children and adolescents diagnosed with temporomandibular
      disorders (TMDs). The sample was selected from four public schools in Piracicaba,
      Sao Paulo, Brazil. Of the 289 participants recruited, aged 8-14 years old, 46
      were placed into the TMD group. TMD was diagnosed using Axis I of the Research
      Diagnostic Criteria for Temporomandibular Disorders (2011). Oro-facial functions
      were evaluated using the Nordic Orofacial Test-Screening (NOT-S), which involves
      both an interview and a clinical examination. BF was measured using a digital
      gnathodynamometer. Age and body mass index (BMI) were also considered. The data
      were analysed by the following tests: Kolmogorov-Smirnov test, Student's t-test,
      Spearman and Pearson coefficients, Qui-square test, Fisher's exact or binomial
      test, as indicated. Moreover, univariate and multivariable logistic regression
      were applied. For the TMD group, scores associated with NOT-S interview and NOT-S
      total were higher than for the control group (P = 0.033 and P = 0.0062,
      respectively). No differences in BF between genders or groups (P > 0.05) were
      detected. Variables included in the multivariate logistic regression were BMI and
      NOT-S total. Based on this analysis, NOT-S total was associated with TMDs.
      Reported sensory function was the specific domain within NOT-S interview that
      established the significant difference between the groups (P = 0.021). The TMD
      group also had a greater number of alterations in the face-at-rest domain of the
      NOT-S exam (P = 0.007). Concluding, it did not detect an association between TMDs
      and either dentition phase or BF. Instead, BF correlated with age and BMI. Oro
      facial dysfunction was associated with TMD in the studied sample, but this
      association may be bidirectional, requiring further researches.

PMID- 24661100
TI  - Challenging the paradigm: anthropological perspectives on HIV as a chronic
      disease.
AB  - Recently HIV has been framed as a 'manageable' chronic disease in contexts in
      which access to effective care is reliable. The chronic disease paradigm
      emphasizes self-care, biomedical disease management, social normalization, and
      uncertainty. Data from a longitudinal study of patients (N = 949) in HIV care at
      two sites in Uganda, collected through semistructured interviews and ethnographic
      data, permit examination of the salience of this model in a high burden, low
      resource context struggling to achieve the promise of a manageable HIV epidemic.
      Our data highlight the complexity of the emerging social reality of long-term
      survival with HIV. Participants struggle to manage stigma as well as to meet the
      costs involved in care seeking. In these settings, economic vulnerability leads
      to daily struggles for food and basic services. Reconceptualizing the chronic
      disease model to accommodate a 'social space,' recognizing this new social
      reality will better capture the experience of long-term survival with HIV. 

PMID- 24661103
TI  - RH and H2 production in reactions between ROH and small molybdenum oxide cluster
      anions.
AB  - To test recent computational studies on the mechanism of metal oxide cluster
      anion reactions with water [Ramabhadran, R. O.; et al. J. Phys. Chem. Lett. 2010,
      1, 3066; Ramabhadran, R. O.; et al. J. Am. Chem. Soc. 2013, 135, 17039], the
      reactivity of molybdenum oxo-cluster anions, Mo(x)O(y)(-) (x = 1 - 4; y <= 3x)
      toward both methanol (MeOH) and ethanol (EtOH) has been studied using mass
      spectrometric analysis of products formed in a high-pressure, fast-flow reactor.
      The size-dependent product distributions are compared to previous Mo(x)O(y)(-) +
      H2O/D2O reactivity studies, with particular emphasis on the Mo2O(y)(-) and
      Mo3O(y)(-) series. In general, sequential oxidation, Mo(x)O(y)(-) + ROH ->
      Mo(x)O(y+1)(-) + RH, and addition reactions, Mo(x)O(y)(-) + ROH -> Mo(x)O(y+1)RH(
      ), largely corresponded with previously studied Mo(x)O(y)(-) + H2O/D2O reactions
      [Rothgeb, D. W., Mann, J. E., and Jarrold, C. C. J. Chem. Phys. 2010, 133,
      054305], though with much lower rate constants than those determined for
      Mo(x)O(y)(-) + H2O/D2O reactions. This finding is consistent with the
      computational studies that suggested that -H mobility on the cluster-water
      complex was an important feature in the overall reactivity. There were several
      notable differences between cluster-ROH and cluster-water reactions associated
      with lower R-OH bond dissociation energies relative to the HO-H dissociation
      energy.

PMID- 24661102
TI  - Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy
      children.
AB  - AIM: The aim of this study was to establish reference intervals in healthy
      children for two novel urinary biomarkers of acute kidney injury, kidney injury
      molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL).
      MATERIALS & METHODS: Urinary biomarkers were determined in samples from children
      in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD)
      and Luminex-based analytical approaches. RESULTS: 95% reference intervals for
      each biomarker in each cohort are presented and stratified by sex or ethnicity
      where necessary, and age-related variability is explored using quantile
      regression. We identified consistently higher NGAL concentrations in females than
      males (p < 0.0001), and lower KIM-1 concentrations in African-Americans than
      Caucasians (p = 0.02). KIM-1 demonstrated diurnal variation, with higher
      concentrations in the morning (p < 0.001). CONCLUSION: This is the first report
      of reference intervals for KIM-1 and NGAL using two analytical methods in a
      healthy pediatric population in both UK and US-based populations.

PMID- 24661104
TI  - MMP-9 inhibitor SB-3CT attenuates behavioral impairments and hippocampal loss
      after traumatic brain injury in rat.
AB  - The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix
      metallopeptidase 9 inhibitor, on behavioral and histological outcomes after
      traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were
      randomly divided into three groups (n=15/group): TBI with SB-3CT treatment, TBI
      with saline, and sham injury. The TBI model was induced by a fluid percussion TBI
      device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered
      intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam
      balance/beam-walk tests) and spatial learning/memory (Morris water maze) were
      assessed on post-operative Days 1-5 and 11-15, respectively. Fluoro-Jade
      staining, immunofluorescence, and cresyl violet-staining were carried out for
      histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively.
      It was shown that TBI can result in significant behavioral deficit induced by
      acute neurodegeneration, increased expression of cleaved caspase-3, and long-term
      neuronal loss. SB-3CT intervention via the current regime provides robust
      behavioral protection and hippocampal neurons preservation from the deleterious
      effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be
      ascertained. It is believed that the current study adds to the growing literature
      in identifying SB-3CT as a potential therapy for human brain injury.

PMID- 24661105
TI  - The clinical value of human leukocyte antigen HLA-DRB1 subtypes associated to
      Graves' disease in Romanian population.
AB  - The aim of this study was to identify the primary susceptibility HLA-DRB1 alleles
      associated with GD in Romanian population and to seek whether specific HLA-DRB1
      haplotypes are associated with differences in the clinical presentation of GD at
      diagnosis. Molecular typing of HLA-DRB1 alleles was performed in 77 Romanian
      Caucasian GD patients and 445 racially matched controls. In GD patients, age,
      presence of eye disease, goiter grade, autoantibody status and titer, TSH, FT4,
      FT3, TT3 levels were recorded at diagnosis. The allelic frequencies of HLA
      DRB1*03 (41.55% vs. 17.75%, p < 0.0001, chi(2) = 20.81) and DRB1*11 (42.85% vs.
      30.56%, p = 0.045, chi(2) = 3.98)were higher, whereas those of HLA-DRB1*01(3.89%
      vs. 16.40%, p = 0.007, chi(2) = 7.281) and DRB1*15 (10.38% vs. 21.34%, p = 0.038,
      chi(2) = 4.309)were lower in GD patients than in controls. FT4/TT3 ratio (p =
      0.015) and anti-thyroglobulin antibodies (p = 0.024) were higher in *03/11
      patients compared to *X/X, *11/Z, *03/Y patients (where X is any other allele
      than *03 and *11, Y is any other allele than *11, Z is any other allele than
      *03). In conclusion, HLA-DRB1*03 and DRB1*11 may be the primary susceptibility
      HLA-DRB1 alleles associated with GD in Romanian population, whereas HLA-DRB1*01
      and DRB1*15 seem to be protective. At diagnosis, HLA-DRB1*03/11 GD patients had
      higher FT4/TT3 ratio and anti-thyroglobulin antibody levels.

PMID- 24661106
TI  - New pharmacological treatment options for chronic constipation.
AB  - INTRODUCTION: A number of new medications were recently demonstrated to be more
      effective than placebo in treating chronic constipation, including the intestinal
      chloride channel activator lubiprostone, the prokinetic selective 5-HT4 receptor
      agonist prucalopride and the guanylate cyclase-C agonist linaclotide. Recent
      publications have also revisited traditional laxatives like PEG. Moreover, a
      number of pharmacological treatments are in development and these include another
      guanylate cyclase-C agonist, plecanatide and an ileal bile acid transporter
      inhibitor, elobixibat. AREAS COVERED: This review focuses on the pharmacology,
      efficacy and safety profile of prucalopride, linaclotide, plecanatide and
      elobixibat. EXPERT OPINION: The possible present or future clinical application
      of prucalopride, linaclotide, plecanatide and elobixibat in both chronic
      constipation and irritable bowel syndrome with constipation is reported, and some
      considerations on the possible role of PEG taking into account recent literature
      are advanced.

PMID- 24661108
TI  - Exploring five common assumptions on Attention Deficit Hyperactivity Disorder.
AB  - The number of children diagnosed with attention deficit hyperactivity disorder
      (ADHD) and treated with medication is steadily increasing. The aim of this paper
      was to critically discuss five debatable assumptions on ADHD that may explain
      these trends to some extent. These are that ADHD (i) causes deviant behaviour,
      (ii) is a disease, (iii) is chronic and (iv) is best treated by medication and
      (v) that classification should precede treatment. CONCLUSION: We argue that ADHD
      is not a disease, not the cause of deviant behaviour and in most cases not
      chronic. Treatment for attention and hyperactivity problems could start with
      psychosocial interventions and without a diagnostic label. A stepped diagnosis
      approach may reduce overdiagnosis without risking undertreatment.

PMID- 24661107
TI  - Effect of low-level laser on guided tissue regeneration performed with equine
      bone and membrane in the treatment of intrabony defects: a clinical study.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the clinical results
      of guided tissue regeneration (GTR) after the application of equine bone and
      membrane alone or combined with low-level laser therapy (LLLT) for the treatment
      of periodontal defects. MATERIALS AND METHODS: This study was an intra-individual
      longitudinal study of 6 months' duration conducted using a split-mouth and
      randomized design. In 13 periodontitis patients with bilateral intrabony
      periodontal defects, while one defect site was treated with GTR plus LLLT (1064
      nm, 100 mW, with energy density of 4 J/cm(2)), the contralateral defect site was
      treated with guided GTR alone. GTR was performed with a combination of equine
      bone and membrane. LLLT was used both intra- and postoperatively. Clinical
      probing depth (PPD), clinical attachment level (CAL), clinical gingival recession
      level (REC), plaque index (PI) score, and sulcus blooding index (SBI) score were
      recorded at the time of surgery, and at the 3rd and 6th months after operation.
      RESULTS: The treatment of periodontal intrabony defects with equine bone and
      membrane in the operation of GTR alone or GTR plus LLLT in combination led to
      statistically significant PPD reduction, CAL gain, and lower SBI score at the end
      of the study (p<0.05). In addition, between the two groups, GTR plus LLLT
      resulted in statistically significant lower REC (p=0.025), lower SBI (p=0.008)
      score, more reduction of PPD (p=0.009) and CAL gain (p=0.002) compared with GTR
      alone at 6th month control. CONCLUSIONS: This study showed that GTR is an
      effective treatment for periodontal regeneration, and that LLLT may improve the
      effects of GTR in the treatment of periodontal defects.

PMID- 24661109
TI  - Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with
      enhanced bioavailability potential.
AB  - BACKGROUND: Trans-resveratrol (t-RVT) is a potent antioxidant. The drug suffers
      enterohepatic recirculation and extensive first-pass metabolism by CYP3A4 in
      liver, resulting in very low bioavailability (almost zero). OBJECTIVE: The
      current studies entail a novel formulation approach to develop systematically
      optimized (OPT) nanoparticles (NPs) to enhance the oral bioavailability potential
      using poly (dl-lactide-co-glycolide) (PLGA) of t-RVT and overcome enterohepatic
      recirculation. METHODS: T-RVT-loaded PLGA NPs were prepared by nanoprecipitation
      method. Delineating the NP regions, the amounts of polymer and emulsifier were
      selected as the critical factors for systematically formulating the OPT NPs
      employing 3(2) central composite design. The pharmacokinetics, in vivo
      biodistribution and in situ single-pass intestinal perfusion (SPIP) studies of
      OPT formulation were investigated in male Wistar rats. RESULTS: Augmentation in
      the values of Ka (7.17-fold) and AUC0 - infinity (10.6-fold) indicated
      significant enhancement in the rate and extent of bioavailability by the OPT
      formulation compared to pure drug and marketed product. OPT formulation showed a
      2.78-fold rise in the values of t-RVT concentrations in liver. In situ SPIP
      studies ascribed the significant enhancement in absorptivity and permeability
      parameters of OPT NPs to transport through the Peyer's patches. Successful
      establishment of in vitro/in vivo correlation substantiated the judicious choice
      of the in vitro dissolution milieu for simulating the in vivo conditions.
      CONCLUSION: The studies, therefore, could provide another useful tool for
      successful development of t-RVT NPs and an in vivo approach to designate
      nanoparticulate system of t-RVT with distinctly improved bioavailability and to
      overcome enterohepatic recirculation.

PMID- 24661111
TI  - EGFRIndb: epidermal growth factor receptor inhibitor database.
AB  - BACKGROUND: Aberrant activity of epidermal growth factor receptor (EGFR) family
      proteins has been found to be associated with a number of human cancers including
      that of lung and breast. Consequently, the search for EGFR family inhibitors, a
      well established target of pharmacological and therapeutic value has been
      ongoing. Therefore, over the years several small molecules, which compete for ATP
      in the kinase domain have been synthesised and some of them have proved to be
      effective in attenuating EGFR mediated proliferation. Thus, there exists in
      literature a vast amount of experimental data on EGFR tyrosine kinase inhibitors.
      In this paper, we describe a comprehensive database EGFRIndb that contains
      details of the small molecular inhibitors of EGFR family. DESCRIPTION: EGFRIndb
      is a literature curated database of small synthetic molecular inhibitors of EGFR.
      It consists of 4581 compounds showing in vitro inhibitory activities (IC50, IC80,
      GI50, GI90, EC50, Ki, Kd and percentage inhibition) either against EGFR or its
      different isoforms i.e. Erbb2 (v-erb-b2 avian erythroblastic leukaemia viral
      oncogene homolog 2) and Erbb4 (v-erb-b2 avian erythroblastic leukaemia viral
      oncogene homolog 4) or various mutants. For each compound, database provides
      information on structure, experimentally determined inhibitory activity of
      compound against kinase as well as various cell lines, properties (physical,
      elemental and topological) and drug likeness. Additionally, it provides
      information on irreversible as well as dual inhibitors that have gained
      importance in recent years due to the emergence of clinical resistance to known
      drugs. As compound activity against similar kinases is a measure of its
      selectivity and specificity, the database also provides this information. It also
      provides simple search, advanced search, browse facility as well as a tool for
      structure based searching. CONCLUSION: EGFRIndb gathers biological and chemical
      information on EGFR inhibitors from the literature. It is hoped that it will
      serve as a useful resource in drug discovery and provide data for docking,
      virtual screening and Quantitative structure-activity relationship (QSAR) model
      development to the cancer researchers.

PMID- 24661110
TI  - Utilizing stomach content and faecal DNA analysis techniques to assess the
      feeding behaviour of largemouth bass Micropterus salmoides and bluegill Lepomis
      macrochirus.
AB  - In this study, the feeding behaviour of the non-native invasive predatory fishes
      largemouth bass Micropterus salmoides and bluegill Lepomis macrochirus was
      studied in the Ezura River, a northern tributary of Lake Biwa, Japan. Prey
      composition was estimated based on visual examination of stomach contents and
      faecal DNA analysis to determine feeding habits of these predatory fishes.
      Stomach content analysis showed that native fishes (e.g. ayu Plecoglossus
      altivelis and gobies Rhinogobius spp.) and shrimps (e.g. Palaemon paucidens) were
      the major prey items for M. salmoides, while snails, larval Chironomidae and
      submerged macrophytes were the dominant prey items of L. macrochirus. Micropterus
      salmoides tended to select larger fish in the case of crucian carp Carassius
      spp., but smaller fishes in the case of P. altivelis and Rhinogobius spp. Faecal
      DNA analyses revealed prey compositions similar to those identified in predator
      stomach contents, and identified additional prey species not detected in stomach
      content inspection. This study demonstrated that both stomach content inspection
      and DNA-based analysis bear several inherent shortcomings and advantages. The
      former method is straightforward, although identification of species can be
      inaccurate or impossible, whereas the latter method allows for accurate species
      identification, but cannot distinguish prey size or stage. Hence, integration of
      morphology-based and DNA-based methods can provide more reliable estimates of
      foraging habits of predatory fishes. 

PMID- 24661112
TI  - Regulatory T-cell depletion in donor lymphocyte infusions for haematological
      malignancies: long-term outcomes from a prospective study.

PMID- 24661113
TI  - Recyclable polystyrene-supported siloxane-transfer agent for palladium-catalyzed
      cross-coupling reactions.
AB  - The rational design, synthesis, and validation of a significantly improved
      insoluble polymer-supported siloxane-transfer agent has been achieved that
      permits efficient palladium-catalyzed cross-coupling reactions. The cross-linked
      polystyrene support facilitates product purification with excellent siloxane
      recycling. Drawbacks of a previous polymer-supported siloxane-transfer agent,
      relating to reaction efficiency and polymer stability after repeated cycles, have
      been addressed. 

PMID- 24661114
TI  - Fluorescence and colorimetric chemosensors for fluoride-ion detection.

PMID- 24661115
TI  - Hunting for unexpected post-translational modifications by spectral library
      searching with tier-wise scoring.
AB  - Discovering novel post-translational modifications (PTMs) to proteins and
      detecting specific modification sites on proteins is one of the last frontiers of
      proteomics. At present, hunting for post-translational modifications remains
      challenging in widely practiced shotgun proteomics workflows due to the typically
      low abundance of modified peptides and the greatly inflated search space as more
      potential mass shifts are considered by the search engines. Moreover, most
      popular search methods require that the user specifies the modification(s) for
      which to search; therefore, unexpected and novel PTMs will not be detected. Here
      a new algorithm is proposed to apply spectral library searching to the problem of
      open modification searches, namely, hunting for PTMs without prior knowledge of
      what PTMs are in the sample. The proposed tier-wise scoring method intelligently
      looks for unexpected PTMs by allowing mass-shifted peak matches but only when the
      number of matches found is deemed statistically significant. This allows the
      search engine to search for unexpected modifications while maintaining its
      ability to identify unmodified peptides effectively at the same time. The utility
      of the method is demonstrated using three different data sets, in which the
      numbers of spectrum identifications to both unmodified and modified peptides were
      substantially increased relative to a regular spectral library search as well as
      to another open modification spectral search method, pMatch. 

PMID- 24661116
TI  - Dynamics of leaf water relations components in co-occurring iso- and anisohydric
      conifer species.
AB  - Because iso- and anisohydric species differ in stomatal regulation of the rate
      and magnitude of fluctuations in shoot water potential, they may be expected to
      show differences in the plasticity of their shoot water relations components, but
      explicit comparisons of this nature have rarely been made. We subjected excised
      shoots of co-occurring anisohydric Juniperus monosperma and isohydric Pinus
      edulis to pressure-volume analysis with and without prior artificial rehydration.
      In J. monosperma, the shoot water potential at turgor loss (Psi(TLP)) ranged from
      -3.4 MPa in artificially rehydrated shoots to -6.6 MPa in shoots with an initial
      Psi of -5.5 MPa, whereas in P. edulis mean Psi(TLP) remained at ~ -3.0 MPa over a
      range of initial Psi from -0.1 to -2.3 MPa. The shoot osmotic potential at full
      turgor and the bulk modulus of elasticity also declined sharply with shoot Psi in
      J. monosperma, but not in P. edulis. The contrasting behaviour of J. monosperma
      and P. edulis reflects differences in their capacity for homeostatic regulation
      of turgor that may be representative of aniso- and isohydric species in general,
      and may also be associated with the greater capacity of J. monosperma to
      withstand severe drought.

PMID- 24661117
TI  - Tiara-like octanuclear palladium(II) and platinum(II) thiolates and their
      inclusion complexes with dihalo- or iodoalkanes.
AB  - A tiara-like octanuclear palladium thiolate complex, [Pd(MU-SCH2CO2Me)2]8, that
      has a toroidal structure was synthesized via reactions of either PdCl2 with
      methyl thioglycolate/N,N-diisopropylethylamine (DIEA) (conventional method) or
      [PdCl2(MeCN)2] with m-C6H4(CMe2SCH2CO2Me)2 (alternative method). In the latter
      method, the tiara-like complex formed via the corresponding SCS-pincer complex
      and/or 1:1 PdCl2 and ligand complexes. With respect to the platinum analogues,
      the alternative method efficiently produced the tiara-like octanuclear complex
      [Pt(MU-SCH2CO2Me)2]8 in high purity. Small molecules, such as CH2Cl2, ClCH2CH2Cl,
      CH2Br2, and CH3I, were accommodated in the inner voids of the tiara rings to form
      1:1 inclusion complexes. These complexes are stabilized not only by weak CH...X
      hydrogen bonds (X = Cl or Br) between the methylene protons of four or eight
      axially positioned methoxycarbonylmethyl groups on the tiara rings and the
      halogen atoms of the guest molecules but also by weak coordination of the halogen
      atoms to the transition-metal atoms. 

PMID- 24661118
TI  - Label-free dopamine imaging in live rat brain slices.
AB  - Dopaminergic neurotransmission has been investigated extensively, yet direct
      optical probing of dopamine has not been possible in live cells. Here we image
      intracellular dopamine with sub-micrometer three-dimensional resolution by
      harnessing its intrinsic mid-ultraviolet (UV) autofluorescence. Two-photon
      excitation with visible light (540 nm) in conjunction with a non-epifluorescent
      detection scheme is used to circumvent the UV toxicity and the UV transmission
      problems. The method is established by imaging dopamine in a dopaminergic cell
      line and in control cells (glia), and is validated by mass spectrometry. We
      further show that individual dopamine vesicles/vesicular clusters can be imaged
      in cultured rat brain slices, thereby providing a direct visualization of the
      intracellular events preceding dopamine release induced by depolarization or
      amphetamine exposure. Our technique opens up a previously inaccessible mid
      ultraviolet spectral regime (excitation ~270 nm, emission < 320 nm) for label
      free imaging of native molecules in live tissue.

PMID- 24661119
TI  - Reserve autophagic capacity in alveolar epithelia provides a replicative niche
      for influenza A virus.
AB  - Autophagy contributes to cellular homeostasis through metabolite recycling and
      degradation of cytotoxic protein aggregates and damaged organelles. Although
      recent studies have established that the requirement for basal autophagy is
      largely tissue specific, the importance of autophagy for alveolar epithelial cell
      homeostasis remains an important knowledge gap. In the present study we generated
      two mouse models, with > 90% or > 50% recombination at the Atg5 locus in the
      distal respiratory epithelium, to assess the effect of dose-dependent decreases
      in autophagy on alveolar homeostasis. A 90% decrease in autophagy was well
      tolerated in young adult mice but resulted in alveolar septal thickening and
      altered lung mechanics in aged animals, consistent with accumulation of damage
      over time. By comparison, a 50% decrease in autophagy had no effect on alveolar
      structure or function throughout the murine life span, indicating that basal
      autophagy in this compartment exceeds that required for homeostasis. A 50%
      decrease in autophagy in the bronchoalveolar epithelium significantly attenuated
      influenza A/H3N2 viral replication, leading to improved lung structure and
      function and reduced morbidity and mortality after infection. The reserve of
      autophagic capacity in the alveolar epithelium may provide a niche for
      replication of influenza A virus. 

PMID- 24661121
TI  - Myelopathy mimicking subacute combined degeneration in a Down syndrome patient
      with methotrexate treatment for B lymphoblastic leukemia: report of an autopsy
      case.
AB  - We report clinicopathological features of a 23-year-old woman with Down syndrome
      (DS) presenting with subacute myelopathy treated with chemotherapy, including
      intravenous and intrathecal administration of methotrexate (MTX), and with
      allogenic bone-marrow transplantation for B lymphoblastic leukemia. Autopsy
      revealed severe demyelinating vacuolar myelopathy in the posterior and lateral
      columns of the spinal cord, associated with macrophage infiltration, marked
      axonal loss and some swollen axons. Pathological changes of posterior and lateral
      columns were observed from the medulla oblongata to lumbar cord. Proximal
      anterior and posterior roots were preserved. Cerebral white matter was relatively
      well preserved. There were no vascular lesions or meningeal dissemination of
      leukemia. Longitudinal extension of cord lesions was extensive, unlike typical
      cases of subacute combined degeneration (SACD), but distribution of lesions and
      histological findings were similar to that of SACD. DS patients show heightened
      sensitivity to MTX because of their genetic background. Risk factors for toxic
      myelopathy of DS are discussed, including delayed clearance of MTX despite normal
      renal function, alterations in MTX polyglutamation and enhanced folic acid
      depletion due to gene dosage effects of chromosome 21. Alteration of folate
      metabolism and/or vitamin B12 levels through intravenous or intrathecal
      administration of MTX might exist, although vitamin B12 and other essential
      nutrients were managed using intravenous hyperalimentation. To the best of our
      knowledge, this is the first report of an autopsy case that shows myelopathy
      mimicking SACD in a DS patient accompanied by B lymphoblastic leukemia. The case
      suggests a pathophysiological mechanism of MTX-related myelopathy in DS patients
      with B lymphoblastic leukemia mimicking SACD.

PMID- 24661120
TI  - Two different presentations of sinus of valsalva aneurysm.
AB  - Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can be congenital
      or acquired. We report 2 cases of SVA. The first case involves a 59-year-old male
      presenting with frequent syncope. Echocardiogram revealed a large right SVA
      obstructing the right ventricular outflow tract (RVOT). The second case involves
      a 21-year-old female presenting with sudden onset chest pain and a continuous
      machinery murmur. Echocardiogram revealed a ruptured right SVA into the right
      atrium. Although advanced percutaneous techniques have been implemented in the
      correction of this anomaly, open-heart surgery with or without aortic valve
      replacement remains the treatment of choice. 

PMID- 24661122
TI  - A disease unlike any other? Why HIV remains exceptional in the age of treatment.

PMID- 24661096
TI  - Protein design: toward functional metalloenzymes.

PMID- 24661123
TI  - Electromyographic analysis of masseter and temporal muscles, bite force,
      masticatory efficiency in medicated individuals with schizophrenia and mood
      disorders compared with healthy controls.
AB  - This study aimed to comparatively analyse the electromyographic activity of the
      masseter and temporal muscles at rest and during mandible postural clinical
      conditions (right and left laterality, protrusion and maximum voluntary
      contraction), right and left maximum molar bite forces and the masticatory
      efficiency of individuals with schizophrenia or mood disorders - all medicated
      (medicated groups) compared with control group (healthy volunteers) via
      electromyography. Individuals were distributed into three groups: Group I
      (Schizophrenia - 20 individuals), Group II (mood disorders - 20 individuals) and
      Group III (Control - 40 individuals). Basically, the results were only
      statistically significant for the clinical mandible conditions and bite force.
      The most unsatisfactory results were observed in the medicated groups in relation
      to the control group. The group with mood disorders obtained the most
      unsatisfactory results compared with the group with schizophrenia. It was
      suggested by these observations that the association of mood disorders and
      schizophrenia with medication has negatively affected the stomatognathic system
      in relation to controls when the electromyography and bite force were used for
      the analysis. 

PMID- 24661124
TI  - Optimization and simulation of tandem column supercritical fluid chromatography
      separations using column back pressure as a unique parameter.
AB  - Tandem column supercritical fluid chromatography (SFC) has demonstrated to be a
      useful technique to resolve complex mixtures by serially coupling two columns of
      different selectivity. The overall selectivity of a tandem column separation is
      the retention time weighted average of selectivity from each coupled column.
      Currently, the method development merely relies on extensive screenings and is
      often a hit-or-miss process. No attention is paid to independently adjust
      retention and selectivity contributions from individual columns. In this study,
      we show how tandem column SFC selectivity can be optimized by changing relative
      dimensions (length or inner diameter) of the coupled columns. Moreover, we apply
      column back pressure as a unique parameter for SFC optimization. Continuous
      tuning of tandem column SFC selectivity is illustrated through column back
      pressure adjustments of the upstream column, for the first time. In addition, we
      show how and why changing coupling order of the columns can produce dramatically
      different separations. Using the empirical mathematical equation derived in our
      previous study, we also demonstrate a simulation of tandem column separations
      based on a single retention time measurement on each column. The simulation
      compares well with experimental results and correctly predicts column order and
      back pressure effects on the separations. Finally, considerations on instrument
      and column hardware requirements are discussed. 

PMID- 24661125
TI  - Helmet use and cervical spine injury: a review of motorcycle, moped, and bicycle
      accidents at a level 1 trauma center.
AB  - Helmet use in two-wheeled vehicle accidents is widely reported to decrease the
      rates of death and traumatic brain injury. Previous reports suggest that there
      exists a trade off with helmet use consisting of an increased risk of cervical
      spine injuries. Recently, a review of a national trauma database demonstrated the
      opposite, with reduction in cervical spinal cord injuries in motorcycle crashes
      (MCC). In 2000, the State of Florida repealed its mandatory helmet law to make
      helmet use optional for individuals older than 21 with $10,000 of health
      insurance coverage. To better ascertain the risks of cervical spine injury with
      non-helmet use in all two-wheeled vehicles, we analyzed the University of Florida
      level one trauma center experience. We reviewed the Traumatic injury database
      over a five-year period (January 1, 2005, to July 1, 2010) for all patients
      involved in two-wheeled vehicle accidents. Patients were stratified according to
      vehicle type (motorcycle, scooter, and bicycle), helmet use, and the presence or
      absence of a cervical spine injury. Outcomes were compared for injury severity,
      cervical spine injury, cervical spinal cord injury, and presence of cervical
      spine injuries requiring surgery. Population means were compared using paired t
      test. A total of 1331 patients were identified: 995 involved in motorcycle
      accidents, 87 involved in low-powered scooter accidents, and 249 involved in
      bicycle accidents. Helmet use was variable between each group. One hundred thirty
      five total cervical spine injuries were identified. No evidence was found to
      suggest an increased risk of cervical spine injury or increased severity of
      cervical spine injury with helmet use. This fact, in combination with our
      previous findings, suggest that the law's age and insurance exemption should be
      revoked and a universal helmet law be reinstated in the state of Florida.

PMID- 24661126
TI  - A nanovesicle topical formulation of Bhut Jolokia (hottest capsicum): a potential
      anti-arthritic medicine.
AB  - OBJECTIVES: Bhut Jolokia is a capsicum variety indigenous to Northeast India and
      is recognized as the hottest capsicum variety of the world. The ethnobotanical
      survey revealed that it has potential anti-arthritic activity but its topical
      adverse events restrict its usability. In the present study, the semipurified
      capsaicinoids extract of Bhut Jolokia was formulated as a topical formulation via
      ethosomal nanovesicle approach, which enhanced the acceptability. METHODS:
      Prepared formulation was optimized by surface response methodology and
      characterized for morphology, zeta potential, differential scanning calorimetry
      study and permeation and penetration studies. The experimental formulations were
      characterized on Freunds complete adjuvant-induced chronic arthritis model.
      RESULTS: Ethosomal nanovesicles prepared with the semipurified capsaicinoids
      extract demonstrated good anti-arthritic activity in rat model, superior to
      Thermagel (a marketed formulation of capsaicin) in the reduction of joint
      swelling and pain throughout the observation period. Nanovesicle formulation
      showed better tolerability and acceptance on both animal and human models.
      Results obtained from the study strengthen the potential application of Bhut
      Jolokia semipurified extract in an ethosomal nanovesicle carrier as a topical
      analgesic as well as an anti-arthritic. CONCLUSION: The significant positive
      results, with reduced irritant effect of the semipurified capsaicinoids extract
      of Bhut Jolokia-loaded ethosomal nanovesicle carrier, suggest that it could be
      one of the choices for formulation development in anti-arthritic medicine.

PMID- 24661127
TI  - Helium-neon laser irradiation promotes the proliferation and migration of human
      epidermal stem cells in vitro: proposed mechanism for enhanced wound re
      epithelialization.
AB  - OBJECTIVE: The present study was conducted to investigate the effects of helium
      neon (He-Ne) laser irradiation on the proliferation, migration, and
      differentiation of cultured human epidermal stem cells (ESCs). BACKGROUND DATA: A
      He-Ne laser with a wavelength of 632.8 nm is known to have photobiological
      effects, and is widely used for accelerating wound healing; however, the cellular
      mechanisms involved have not been completely understood. METHODS: The ESCs were
      prepared from human foreskin, and irradiated by using He-Ne laser at 632.8 nm
      with 2 J/cm(2). The ESC proliferation, migration, and differentiation were
      examined by using XTT assay, scratch assay, and flow cytometry technology,
      respectively. The phosphorylation of extracellular signal-regulated kinases (ERK)
      was analyzed by using Western blotting. RESULTS: He-Ne laser irradiation markedly
      promoted cell proliferation and migration accompanied by an increase in the
      phosphorylation of ERK, but did not significantly influence cell differentiation.
      CONCLUSION: Our data indicated that photostimulation with a He-Ne laser resulted
      in a significant increase in human ESC proliferation and migration in vitro,
      which might contribute, at least partially, to accelerated wound re
      epithelialization by low-level laser therapy.

PMID- 24661128
TI  - The effects of oats on the function of gut microflora in children with coeliac
      disease.
AB  - BACKGROUND: Faecal short chain fatty acids (SCFAs) are produced by the gut
      microflora. We have previously reported high faecal SCFA levels in children with
      coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data
      accumulated over recent decades by us and others suggest that wheat-free oats can
      safely be included in a gluten-free diet (GFD). However, concerns have been
      raised with respect to the safety of oats in a subset of coeliacs. AIM: To
      describe faecal SCFA patterns in children with newly diagnosed CD treated for 1
      year with a GFD with or without oats. METHODS: This report is part of a
      randomised, double-blind study on the effect of a GFD containing oats (GFD-oats)
      vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in
      the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after
      1 year on a GFD. Faecal SCFAs were analysed. RESULTS: The GFD-std group had a
      significantly lower total faecal SCFA concentration at 12 months compared with 0
      months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high
      after 1 year on the GFD. The children in the GFD-oats group had significantly
      higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA
      concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std
      group. CONCLUSIONS: Our results indicate that oats do affect the gut microflora
      function, and that some coeliac children receiving oats may develop gut mucosal
      inflammation, that may present a risk for future complications.

PMID- 24661129
TI  - Titanium dioxide nanomaterials for photovoltaic applications.

PMID- 24661130
TI  - Do stocked hatchery-reared juveniles ecologically suppress wild juveniles in
      Salvelinus leucomaenis?
AB  - The dominancy of semi-wild and hatchery-reared white-spotted charr Salvelinus
      leucomaenis juveniles was evaluated using pair-wise enclosure tests and field
      stocking tests. The semi-wild S. leucomaenis originated in a hatchery, being
      stocked into the test stream as eyed-eggs. In the pair-wise enclosure test, the
      semi-wild S. leucomaenis dominated the hatchery S. leucomaenis that were of a
      similar standard length (L(S) ). The semi-wild S. leucomaenis were subordinate to
      hatchery S. leucomaenis that were > 11% larger in LS . In the field stocking
      test, the abundance and growth of semi-wild S. leucomaenis was decreased in the
      presence of larger hatchery S. leucomaenis (14% larger LS ). Taken together,
      these results suggest that larger hatchery S. leucomaenis ecologically suppress
      the smaller semi-wild S. leucomaenis. Salvelinus leucomaenis juveniles that are
      stocked with the intention of supplementing natural populations should be < 10%
      larger than their wild counterparts at the time of stocking to minimize their
      competitive advantage. The semi-wild and hatchery S. leucomaenis used in both
      tests were genetically similar individuals, suggesting that the differences are
      due to the early rearing environment of either a natural stream or hatchery. The
      hatchery S. leucomaenis have lower levels of aggression as a result of selection
      in the hatchery rearing environment. Rearing in a natural stream from the eyed
      egg stage is likely to increase their lowered aggression.

PMID- 24661132
TI  - A latent class distance association model for cross-classified data with a
      categorical response variable.
AB  - In this paper we propose a latent class distance association model for clustering
      in the predictor space of large contingency tables with a categorical response
      variable. The rows of such a table are characterized as profiles of a set of
      explanatory variables, while the columns represent a single outcome variable. In
      many cases such tables are sparse, with many zero entries, which makes
      traditional models problematic. By clustering the row profiles into a few
      specific classes and representing these together with the categories of the
      response variable in a low-dimensional Euclidean space using a distance
      association model, a parsimonious prediction model can be obtained. A generalized
      EM algorithm is proposed to estimate the model parameters and the adjusted
      Bayesian information criterion statistic is employed to test the number of
      mixture components and the dimensionality of the representation. An empirical
      example highlighting the advantages of the new approach and comparing it with
      traditional approaches is presented. 

PMID- 24661133
TI  - Abnormalities of quantities and functions of natural killer cells in severe
      aplastic anemia.
AB  - Severe aplastic anemia (SAA) is a rare disease characterized by severe
      pancytopenia and bone marrow failure. Natural killer (NK) cells are large
      granular lymphocytes derived from hematopoietic stem cells (HSCs) or common
      lymphoid progenitors (CLP). They play a key role in n the innate immunity and
      adaptive immune. In this study, the quantitative and functional changes of
      natural killer (NK) cell subsets in peripheral blood of severe aplastic anemia
      (SAA) patients before and after immunosuppressive therapy (IST) were
      investigated. Results showed that the percentage of NK cells and its subsets in
      peripheral blood lymphocytes was decreased in SAA patients. After IST, the
      percentage of NK cells and their subsets increased dramatically. The median
      expressions of CD158a, NKG2D and NKp46 on NK cells were higher in SAA patients
      compared to that in normal controls, and the expressions of perforin in newly
      diagnosed and recovery SAA patients were higher than that in controls. Therefore,
      we concluded that the decrease of total NK cells, and CD56(bright), CD56(dim) NK
      cell subsets and the higher expressions of NKp46 and perforin on NK cells may
      cause the over-function of T lymphocytes and thus lead to hematopoiesis failure
      in SAA.

PMID- 24661135
TI  - Endoscopic mucosal resection and endoscopic submucosal dissection of epithelial
      neoplasia of the colon.
AB  - Endoscopic mucosal resection (EMR) with curative intent has evolved into a safe
      and effective technique and is currently the gold standard for management of
      large colonic epithelial neoplasms. Piecemeal EMR is associated with a high risk
      of local recurrence requiring vigilant surveillance and repeat interventions.
      Endoscopic submucosal dissection (ESD) was introduced in Japan for the management
      of early gastric cancer, and has recently been described for en bloc resection of
      colonic lesions greater than 20 mm. En bloc resection allows accurate
      histological assessment of the depth of invasion, minimizes the risk of local
      recurrence and helps determine additional therapy. Morphologic classification of
      lesions prior to resection allows prediction of depth of invasion and risk of
      nodal metastasis, allowing selection of the appropriate intervention. This review
      provides an overview of the assessment of epithelial neoplasms of the colon and
      the application of EMR and ESD techniques in their management. 

PMID- 24661134
TI  - Toward the total synthesis of hygrocin B and divergolide C: construction of the
      naphthoquinone-azepinone core.
AB  - A highly regioselective Diels-Alder approach toward the bioactive natural
      products hygrocin B and divergolide C is presented. The route uses an unusual
      benzoquinone-azepinone dienophile prepared in 8 steps from ethyl 8-methoxy-1
      naphthoate, by a route which includes, as key steps, a Birch alkylation and a
      Beckmann rearrangement of a tetralone oxime, both of which are demonstrated on
      multigram scale. The naphthoquinone-azepinone core is suitably functionalized for
      addition of the ansa-chain, found in the natural products. 

PMID- 24661136
TI  - Cold shock protein A plays an important role in the stress adaptation and
      virulence of Brucella melitensis.
AB  - Brucella melitensis is a facultative intracellular pathogen that mainly resides
      within macrophages. The mechanisms employed by Brucella to adapt to harsh
      intracellular environments and survive within host macrophages are not clearly
      understood. Here, we constructed a cspA gene deletion mutant, NIDeltacspA, that
      did not exhibit any discernible growth defect at a normal culture temperature (37
      degrees C) or at a low temperature (15  degrees C). However, expression of the
      cspA gene in Brucella was induced by cold, acidic, and oxidative conditions, as
      determined via quantitative reverse transcription PCR. Unlike its parental
      strain, B. melitensis NI, the NIDeltacspA mutant showed an increased sensitivity
      to acidic and H2 O2 stresses, especially during the mid-log-phase, and these
      stress conditions would presumably be encountered by bacteria during
      intracellular infections. Moreover, macrophage and mouse infection assays
      indicated that the NIDeltacspA mutant fails to replicate in cultured J774.A1
      murine macrophages and is rapidly cleared from the spleens of experimentally
      infected BALB/c mice. These findings suggest that the Brucella cspA gene makes an
      essential contribution to virulence in vitro and in vivo, most likely by allowing
      brucellae to adapt appropriately to the harsh environmental conditions
      encountered within host macrophages. 

PMID- 24661138
TI  - Quantitative proteomic profiling of pleomorphic human sarcoma identifies CLIC1 as
      a dominant pro-oncogenic receptor expressed in diverse sarcoma types.
AB  - Sarcomas are rare forms of cancer with a high unmet clinical need that develop in
      connective tissue, such as muscle, bone, nerves, cartilage, and fat. The outcome
      for patients is poor, with surgery and postoperative radiotherapy the standard
      treatment for patients. A better understanding of the molecular pathology of
      sarcoma may allow for the development of novel therapeutics. There are dozens of
      sarcoma subtypes where there is a need for targetted therapeutics, with the most
      commonly studied including Ewing's sarcoma and osteosarcoma. Here we initiate a
      proteomics-based target-discovery program to define "dominant" pro-oncogenic
      signaling targets in the most common sarcoma in adults: high-grade pleiomorphic
      soft tissue sarcoma. We have carried out a proteome screen using tandem mass tag
      isobaric labeling on three high-grade undifferentiated pleomorphic sarcoma
      biopsies from different tissue sites. We identified the commonly dysregulated
      proteins within the three sarcomas and further validated the most penetrant
      receptor as CLIC1, using immunohistochemistry arising from two different
      population cohorts representing over 300 patients. The dominant expression of
      CLIC1 in a broad range of human sarcomas suggests that studying this relatively
      unexplored signaling pathway might provide new insights into disease mechanism
      and facilitate the development of new CLIC1 targeted therapeutics. 

PMID- 24661139
TI  - Gastrodin alleviates memory deficits and reduces neuropathology in a mouse model
      of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disease,
      characterized by excessive accumulation of amyloid-beta (Abeta) and activation of
      microglia cells and astrocytes. In this research, we evaluated whether gastrodin,
      an active component isolated from the rhizome of Gastrodia elata, has
      neuroprotective effects in a mouse model of AD, Tg2576 mice. Treatment of
      gastrodin (60 mg/kg for 15 days) significantly improved memory impairments in the
      Morris water maze test and probe test. Moreover, immunohistochemical and ELISA
      results indicated that gastrodin significantly attenuated Abeta deposition and
      glial activation in brains of these transgenic mice. These findings suggested
      that gastrodin exerted neuroprotective activity via anti-inflammatory and anti
      amyloidogenic effects and that gastrodin may be a potential option for AD
      therapy.

PMID- 24661140
TI  - Limitations and strengths of doppler/echo pulmonary artery systolic pressure
      right heart catheterization correlations: a systematic literature review.
AB  - AIMS: Because many recent studies have questioned the accuracy of Doppler
      echocardiography (D) in determining pulmonary artery systolic pressure (PASP), we
      performed a detailed literature analysis attempting add clarity. METHODS AND
      RESULTS: Studies through 2011 comparing D and right heart catheterization (RHC)
      PASP, with at least 25 studied patients and reporting correlation coefficients
      (r) were identified. Patient demographics, study characteristics, the percent of
      patients studied for left or right heart pathologies, and study biases were
      determined. After adjusting for differing study sizes, each study's r value was
      used as a single datapoint and dichotomized above or below the entire cohort's
      mean values. From 32 studies 2604 D-RHC parings were reported. Their overall
      weighted r was 0.68 +/- 0.19. Poorer correlations were found for right heart
      pathologies compared to left heart pathologies (r = 0.58 vs. 0.84, P < 0.001) and
      for normal PASP patients in a study compared to abnormal PASP patients (r = 0.55
      vs. 0.82, P < 0.001). Studies with predominately right heart pathology had a
      significantly greater D-RHC time difference, fewer successful D determinations, a
      greater percentage of normal PASPs on RHC, and more between-method differences
      >10 mmHg. Metaregression analyses indicated that both right heart pathology
      predominance and a greater percent of normal PASPs on RHC remained associated
      with poorer correlations. CONCLUSIONS: D PASP-RHC correlations were high and
      between-method differences less in patients with left heart pathology but were
      poorer for right heart diseases and studies with proportionately more normal
      PASPs on RHC for which further study is needed.

PMID- 24661137
TI  - Global reprogramming of transcription and metabolism in Medicago truncatula
      during progressive drought and after rewatering.
AB  - Medicago truncatula is a model legume forage crop native to the arid and semi
      arid environments of the Mediterranean. Given its drought-adapted nature, it is
      an ideal candidate to study the molecular and biochemical mechanisms conferring
      drought resistance in plants. Medicago plants were subjected to a progressive
      drought stress over 14 d of water withholding followed by rewatering under
      controlled environmental conditions. Based on physiological measurements of plant
      water status and changes in morphology, plants experienced mild, moderate and
      severe water stress before rehydration. Transcriptome analysis of roots and
      shoots from control, mildly, moderately and severely stressed, and rewatered
      plants, identified many thousands of genes that were altered in expression in
      response to drought. Many genes with expression tightly coupled to the plant
      water potential (i.e. drought intensity) were identified suggesting an
      involvement in Medicago drought adaptation responses. Metabolite profiling of
      drought-stressed plants revealed the presence of 135 polar and 165 non-polar
      compounds in roots and shoots. Combining Medicago metabolomic data with
      transcriptomic data yielded insight into the regulation of metabolic pathways
      operating under drought stress. Among the metabolites detected in drought
      stressed Medicago plants, myo-inositol and proline had striking regulatory
      profiles indicating involvement in Medicago drought tolerance. 

PMID- 24661141
TI  - Automatic registration of mass spectrometry imaging data sets to the Allen brain
      atlas.
AB  - Mass spectrometry imaging holds great potential for understanding the molecular
      basis of neurological disease. Several key studies have demonstrated its ability
      to uncover disease-related biomolecular changes in rodent models of disease, even
      if highly localized or invisible to established histological methods. The high
      analytical reproducibility necessary for the biomedical application of mass
      spectrometry imaging means it is widely developed in mass spectrometry
      laboratories. However, many lack the expertise to correctly annotate the complex
      anatomy of brain tissue, or have the capacity to analyze the number of animals
      required in preclinical studies, especially considering the significant
      variability in sizes of brain regions. To address this issue, we have developed a
      pipeline to automatically map mass spectrometry imaging data sets of mouse brains
      to the Allen Brain Reference Atlas, which contains publically available data
      combining gene expression with brain anatomical locations. Our pipeline enables
      facile and rapid interanimal comparisons by first testing if each animal's tissue
      section was sampled at a similar location and enabling the extraction of the
      biomolecular signatures from specific brain regions. 

PMID- 24661142
TI  - Transport in asymmetrically coupled donor-based silicon triple quantum dots.
AB  - We demonstrate serial electron transport through a donor-based triple quantum dot
      in silicon fabricated with nanoscale precision by scanning tunnelling microscopy
      lithography. From an equivalent circuit model, we calculate the electrochemical
      potentials of the dots allowing us to identify ground and excited states in
      finite bias transport. Significantly, we show that using a scanning tunnelling
      microscope, we can directly demonstrate that a ~1 nm difference in interdot
      distance dramatically affects transport pathways between the three dots. 

PMID- 24661143
TI  - A model of plant isoprene emission based on available reducing power captures
      responses to atmospheric CO2.
AB  - We present a unifying model for isoprene emission by photosynthesizing leaves
      based on the hypothesis that isoprene biosynthesis depends on a balance between
      the supply of photosynthetic reducing power and the demands of carbon fixation.
      We compared the predictions from our model, as well as from two other widely used
      models, with measurements of isoprene emission from leaves of Populus nigra and
      hybrid aspen (Populus tremula * P. tremuloides) in response to changes in leaf
      internal CO2 concentration (C(i)) and photosynthetic photon flux density (PPFD)
      under diverse ambient CO2 concentrations (C(a)). Our model reproduces the
      observed changes in isoprene emissions with C(i) and PPFD, and also reproduces
      the tendency for the fraction of fixed carbon allocated to isoprene to increase
      with increasing PPFD. It also provides a simple mechanism for the previously
      unexplained decrease in the quantum efficiency of isoprene emission with
      increasing C(a). Experimental and modelled results support our hypothesis. Our
      model can reproduce the key features of the observations and has the potential to
      improve process-based modelling of isoprene emissions by land vegetation at the
      ecosystem and global scales.

PMID- 24661145
TI  - Erysipelothrix rhusiopathiae contamination in the poultry house environment
      during erysipelas outbreaks in organic laying hen flocks.
AB  - This study investigated organic laying hen farms for the presence of
      Erysipelothrix rhusiopathiae in the house environment and from potential carriers
      (i.e. insects and mice) during ongoing erysipelas outbreaks, and compared the
      obtained isolates with those from laying hens. The samples were investigated by
      selective culture followed by species-specific polymerase chain reaction on
      cultures. E. rhusiopathiae was isolated from the spleen, jejunal contents,
      manure, dust and swabs from water nipples. Three more samples from the house
      environment tested positive by polymerase chain reaction compared with selective
      culture alone. Selected isolates were investigated by pulsed-field gel
      electrophoresis (PFGE) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS). One farm was represented by isolates
      from laying hens only, and one of these isolates differed in one PFGE band from
      the others. Different banding patterns were observed for isolates from laying
      hens and manure on one farm. On the remaining two farms, the isolates from the
      house environment and laying hens were identical but differed between farms.
      Outbreaks reoccurred in the next flock on two of the farms, and different PFGE
      types were isolated from consecutive flocks. Our results suggest an external
      source of infection, which would explain the previously reported increased risk
      of outbreaks in free-range flocks. Contaminated manure and dust may represent
      sources of transmission. For the isolates, MALDI-TOF MS and biochemical typing
      results were in agreement but, since the type strain of Erysipelothrix
      tonsillarum was typed as E. rhusiopathiae using MALDI-TOF MS, further studies
      into this method are needed. 

PMID- 24661146
TI  - Advances in understanding Alzheimer's disease, and the contributions of current
      Alzheimer research: ten years on and beyond.

PMID- 24661147
TI  - EEG upper/low alpha frequency power ratio and the impulsive disorders network in
      subjects with mild cognitive impairment.
AB  - The ventral striatum-nucleus accumbens network has been associated with impulsive
      behavior in subjects with early cognitive impairment; in Alzheimer's disease (AD)
      modifications of basal ganglia have been also demonstrated. Moreover, the
      increase of EEG alpha3/alpha2 frequency power ratio has been investigated as EEG
      marker in subjects with mild cognitive impairment (MCI) who will develop AD. In
      the present study we have detected the relationship between upper alpha/low alpha
      ferquency power ratio and specific gray matter (GM) changes in the basal ganglia
      in subjects with MCI. Electroencefalographic (EEG) recording and high resolution
      3D magnetic resonance imaging (MRI) were taken in 74 MCI subjects. In each
      subject the alpha3/alpha2 EEG frequency power ratio was estimated as EEG
      biomarker. Three groups were obtained according to increasing tertiles values of
      the biomarker. Through the Voxel Based Morphometry (VBM) technique, GM density
      differences between groups were evaluated. Results show that subjects with lower
      a3/a2 and middle a3/a2 ratio ratio showed greater gray matter reduction in the
      Nucleus Accumbens and the head of Caudate Nucleus as compared to subjects with
      higher a3/a2 ratio. Our study indicates that the a3/a2 frequency power ratio was
      associated with increase of grey matter density inside the impulsivity network of
      MCI patients more likely develop AD. 

PMID- 24661148
TI  - Assessing severity of illness and outcomes of treatment in children with Chronic
      Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): a systematic review of
      patient-reported outcome measures (PROMs).
AB  - Chronic Fatigue Syndrome or Myalgic Encephalomyelitis (CFS/ME) in children is
      characterized by persistent or recurrent debilitating fatigue which results in a
      substantial reduction in activity. There is a growing interest in the use of
      questionnaires, or patient-reported outcome measures (PROMs), to assess how
      patients function and feel in relation to their health and associated healthcare.
      However, guidance for PROM selection for children with CFS/ME does not exist. We
      reviewed the quality and acceptability of PROMs used with children with CFS/ME to
      inform recommendations for practice. We conducted a systematic review of PROMs
      completed by children with CFS/ME. The quality of the evaluative studies and the
      reviewed measures were assessed against recommended criteria using an appraisal
      framework and the COnsensus-based Standards for the selection of health
      Measurement INstruments (COSMIN) checklist. We sought evidence of measurement
      (reliability, validity, responsiveness, interpretability, data quality) and
      practical properties (acceptability, relevance, feasibility). Sixteen articles
      were included in the review, providing evidence of reliability and/or validity
      for 13 PROMs. Of these, five were child-specific (one health-related quality-of
      life; four emotional well-being) and eight were not (four emotional well-being,
      three fatigue-specific; and one generic). All measures had limited evidence of
      measurement properties and no evidence of practical properties. Recommendations
      for patient-reported assessment are difficult to make because of limited evidence
      of the quality and acceptability of PROMs for children with CFS/ME. The appraisal
      method highlighted significant methodological and quality issues which must be
      addressed in future research. There is a lack of qualitative evidence describing
      the outcomes of healthcare that are important to children with CFS/ME, and the
      relevance or appropriateness of available measures. Future PROM development and
      evaluation in this group must seek to involve children collaboratively to ensure
      that the outcomes that children care about are assessed in an acceptable way. 

PMID- 24661149
TI  - Synthesis of the pentacylic core of (+)-salvileucalin B.
AB  - A concise preparation of the prochiral pentacyclic core of (+)-salvileucalin B is
      presented. The key feature in the synthesis is the Cu-catalyzed intramolecular
      cyclopropanation of a symmetrical indane-derived alpha-diazo beta-keto ester.
      This symmetry is carried through the remainder of the synthesis. This practical
      approach could allow the ready preparation of derivatives for further chemical
      and biological studies of this class of natural products. 

PMID- 24661150
TI  - The importance of patient compliance with insulin pens: how can a new user
      friendly pen help?
AB  - FlexTouch(r) (FT) is a new prefilled insulin pen with the unique characteristic
      of no extendable push button at any dose setting and consequently a low
      activation force. Its technical features along with health care professionals'
      and patients' preferences in comparison to other traditionally used devices for
      insulin delivery have already been investigated. Recently, a study of injection
      force and accuracy using FT in the delivery of new basal insulin has compared FT
      with the insulin pens KwikPen(r) and SoloStar(r) and has shown that FT exhibits
      preciseness in insulin delivery of all insulin formulations and a significantly
      lower activation force than the other two insulin injectors. Despite the very
      promising characteristics of this new device, important questions remain to be
      answered, mainly the possible promotion of treatment adherence and the notion of
      confidence in self-administration of insulin. Moreover, an analysis of patients'
      perception on injecting higher doses with FT in comparison to other insulin
      injectors would be useful.

PMID- 24661151
TI  - Alendronate-induced atypical bone fracture: evidence that the drug inhibits
      osteogenesis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Alendronate (ALN) is used for the treatment of post
      menopausal osteoporosis. By reducing bone turnover, it increases bone mineral
      density. However, recent reports suggest an increased risk of atypical bone
      fractures after long-term ALN administration. Despite its well-known anti
      osteoclastic activity, it is unclear whether ALN also suppresses human
      mesenchymal stem cell (hMSC)-mediated osteogenesis, thus possibly resulting in
      atypical bone fragility. We hypothesized that ALN does this and we look at its in
      vitro effects on osteogenesis. METHODS: Morphological analysis, reverse
      transcriptase polymerase chain reaction, cell viability, alkaline phosphatase
      (ALP) activity and mineralization assays were investigated in hMSCs treated with
      a wide range of ALN. RESULTS AND DISCUSSION: After treatment with high
      concentrations of ALN for 3 and 7 days, cell viability was significantly reduced
      and cell morphology was altered. Osteogenic differentiation of hMSCs was also
      substantially suppressed as demonstrated by decreased ALP activity although ALN
      did not affect osteogenic-related genes tested. Furthermore, ALN at all
      concentrations tested drastically inhibited alizarin red S-positive mineralized
      matrix. WHAT IS NEW AND CONCLUSION: ALN has a strong inhibitory effect on hMSC
      mediated osteogenesis by suppressing cell proliferation, osteoblast
      differentiation and function. The insight gained may help in the development of
      safer alternatives.

PMID- 24661152
TI  - Alteration in synaptic junction proteins following traumatic brain injury.
AB  - Extensive research and scientific efforts have been focused on the elucidation of
      the pathobiology of cellular and axonal damage following traumatic brain injury
      (TBI). Conversely, few studies have specifically addressed the issue of synaptic
      dysfunction. Synaptic junction proteins may be involved in post-TBI alterations,
      leading to synaptic loss or disrupted plasticity. A Synapse Protein Database on
      synapse ontology identified 109 domains implicated in synaptic activities and
      over 5000 proteins, but few of these demonstrated to play a role in the synaptic
      dysfunction after TBI. These proteins are involved in neuroplasticity and
      neuromodulation and, most importantly, may be used as novel neuronal markers of
      TBI for specific intervention.

PMID- 24661153
TI  - The real mental illnesses: Susan Nolen-Hoeksema (1959-2013) in memoriam.
AB  - Susan Nolen-Hoeksema's life work concerned rumination, gender differences in
      depression, and the "transdiagnostic" processes in mental illness. The articles
      in this special section expand on these themes. Her work on transdiagnostic
      processes leads us to consider that the real mental illnesses are not the
      congeries of symptoms in the Diagnostic and Statistical Manual of Mental
      Disorders, but these processes themselves.

PMID- 24661154
TI  - Positive activities as protective factors against mental health conditions.
AB  - Applying Nolen-Hoeksema and Watkins's (2011) transdiagnostic risk factor
      heuristic to our work on positive activities (i.e., practices that characterize
      naturally happy people, like expressing gratitude and practicing generosity), we
      propose that such activities may serve as protective factors that mitigate
      proximal risk factors both directly and by intervening with the mechanisms that
      give rise to them. First, we discuss theoretical and empirical support for the
      importance of well-being and the mechanisms that explain how positive activities
      promote well-being (by boosting positive emotions, positive thoughts, positive
      behaviors, and need satisfaction; Lyubomirsky & Layous, 2013). Second, we outline
      examples of how positive activities can mitigate two particular proximal risk
      factors (rumination and loneliness) and counteract environmental triggers (i.e.,
      moderators) that might amplify them (e.g., through adaptive coping). Third, we
      argue that positive activities can be taught to youth to instill positive
      patterns of emotions, thoughts, and behaviors that may serve as protective
      factors over the course of their lifetimes. Lastly, we propose that certain
      positive activities might be particularly well-suited to certain individuals and
      to specific risk factors.

PMID- 24661156
TI  - A habit-goal framework of depressive rumination.
AB  - Rumination has been robustly implicated in the onset and maintenance of
      depression. However, despite empirically well-supported theories of the
      consequences of trait rumination (response styles theory; Nolen-Hoeksema, 1991),
      and of the processes underlying state episodes of goal-oriented repetitive
      thought (control theory; Martin & Tesser, 1989, 1996), the relationship between
      these theories remains unresolved. Further, less theoretical and clinical
      attention has been paid to the maintenance and treatment of trait depressive
      rumination. We propose that conceptualizing rumination as a mental habit (Hertel,
      2004) helps to address these issues. Elaborating on this account, we propose a
      framework linking the response styles and control theories via a theoretical
      approach to the relationship between habits and goals (Wood & Neal, 2007). In
      this model, with repetition in the same context, episodes of self-focused
      repetitive thought triggered by goal discrepancies can become habitual, through a
      process of automatic association between the behavioral response (i.e.,
      repetitive thinking) and any context that occurs repeatedly with performance of
      the behavior (e.g., physical location, mood), and in which the repetitive thought
      is contingent on the stimulus context. When the contingent response involves a
      passive focus on negative content and abstract construal, the habit of depressive
      rumination is acquired. Such habitual rumination is cued by context independent
      of goals and is resistant to change. This habit framework has clear treatment
      implications and generates novel testable predictions.

PMID- 24661155
TI  - Rumination as a transdiagnostic factor underlying transitions between
      internalizing symptoms and aggressive behavior in early adolescents.
AB  - The high degree of comorbidity among mental disorders has generated interest in
      identifying transdiagnostic processes associated with multiple types of
      psychopathology. Susan Nolen-Hoeksema conceptualized rumination as one such
      transdiagnostic process associated with depression, anxiety, substance abuse,
      binge eating, and self-injurious behavior. The degree to which rumination
      accounts for the co-occurrence of internalizing and externalizing
      psychopathology, however, has never been tested. We used a sample of early
      adolescents (N = 1,065) assessed at 3 time points spanning 7 months to examine
      (a) the reciprocal prospective associations between rumination and aggressive
      behavior in adolescents, (b) whether rumination explained the longitudinal
      associations of aggressive behavior with depression and anxiety symptoms, and (c)
      gender differences in these associations. Rumination predicted increases over
      time in aggressive behavior, and aggression was associated with increases in
      rumination over time only for boys. Rumination fully mediated the longitudinal
      association of aggression with subsequent anxiety symptoms and of both depression
      and anxiety symptoms with subsequent aggression in boys but not girls. Rumination
      did not explain the association between aggression and subsequent depressive
      symptoms for either boys or girls. These findings provide novel evidence for the
      role of rumination as a transdiagnostic factor underlying transitions between
      internalizing and externalizing symptoms among males during early adolescence.
      Interventions aimed at reducing rumination may have beneficial influences on
      multiple forms of psychopathology and on the development of comorbidity.
      (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24661158
TI  - Transdiagnostic processes in psychopathology: in memory of Susan Nolen-Hoeksema.
AB  - This special section honors Dr. Susan Nolen-Hoeksema's influential work dedicated
      to improving our understanding of psychopathology. Dr. Nolen-Hoeksema adopted a
      transdiagnostic perspective to identify mechanisms that underlie many emotional
      disorders such as cognitive processes and emotion regulation. Her work on the
      role of rumination and the role of gender differences in psychopathology not only
      advanced our understanding of important risk factors that cut across disorders
      but also inspired the development of improved prevention and intervention
      efforts.

PMID- 24661157
TI  - Neural substrates of trait ruminations in depression.
AB  - Rumination in depression is a risk factor for longer, more intense, and harder-to
      treat depressions. But there appear to be multiple types of depressive rumination
      whether they all share these vulnerability mechanisms, and thus would benefit
      from the same types of clinical attention is unclear. In the current study, we
      examined neural correlates of empirically derived dimensions of trait rumination
      in 35 depressed participants. These individuals and 29 never-depressed controls
      completed 17 self-report measures of rumination and an alternating emotion
      processing/executive-control task during functional MRI (fMRI) assessment. We
      examined associations of regions of interest--the amygdala and other cortical
      regions subserving a potential role in deficient cognitive control and
      elaborative emotion-processing--with trait rumination. Rumination of all types
      was generally associated with increased sustained amygdala reactivity. When
      controlling for amygdala reactivity, distinct activity patterns in hippocampus
      were also associated with specific dimensions of rumination. We discuss the
      possibly utility of targeting more basic biological substrates of emotional
      reactivity in depressed patients who frequently ruminate.

PMID- 24661159
TI  - Autobiographical episodic memory in major depressive disorder.
AB  - Autobiographical memory in major depression has been characterized as
      overgeneralized, with patients recalling few episodic details, prioritizing
      general schematic events. However, whether this effect reflects impaired episodic
      or semantic memory, or domain-general cognitive processes, is unknown. We used
      the Autobiographical Interview (Levine, Svoboda, Hay, Winocur, & Moscovitch,
      2002) to derive episodic and semantic contributions to autobiographical memory in
      patients with severe major depression. We also assessed memory for public events
      and famous people. Depressed patients were impaired on episodic, but not
      semantic, autobiographical memory from 2 weeks to 10 years before testing. They
      were also impaired on memory for public events, possibly because they followed
      the news less than controls. Patients' memory for famous names was not impaired,
      although this was strongly associated with non-episodic memories to a greater
      degree than in controls. The findings suggest a specific impairment of episodic
      autobiographical memory in depression that is not fully accounted for by domain
      general processes involved in strategic retrieval.

PMID- 24661160
TI  - Brooding rumination and heart rate variability in women at high and low risk for
      depression: group differences and moderation by COMT genotype.
AB  - There is growing evidence that rumination, perhaps specifically brooding
      rumination, is a core feature of depression and that it contributes to the
      development and maintenance of the disorder. A separate line of research has
      highlighted the role played by heart rate variability (HRV). Both brooding
      rumination and HRV appear to be driven by disruption in the same neural circuit,
      heightened amygdala reactivity combined with decreased prefrontal control, and
      both are highlighted in different units of analysis as reflecting the Research
      Domain Criteria (RDoC) construct of Loss. However, little is known about the
      relation among these variables. In the current study, we predicted that higher
      levels of brooding rumination would be associated with lower levels of HRV and
      that women at high risk for future depression (i.e., those with a history of past
      major depressive disorder [MDD]) would exhibit higher levels of brooding and
      lower levels of HRV. We also examined genetic influences on the variables in this
      model. We predicted that COMT Val158Met genotype, which has been linked to
      heightened amygdala reactivity and deficits in prefrontal functioning, would be
      associated with brooding rumination and HRV, particularly among women with a
      history of past MDD. The results largely supported our hypotheses, providing
      additional support for relations among the different units of analysis for the
      Loss construct.

PMID- 24661161
TI  - Abnormal proactive and reactive cognitive control during conflict processing in
      major depression.
AB  - According to the Dual Mechanisms of Control framework, cognitive control consists
      of two complementary components: proactive control refers to anticipatory
      maintenance of goal-relevant information, whereas reactive control acts as a
      correction mechanism that is activated when a conflict occurs. Possibly, the well
      known diminished inhibitory control in response to negative stimuli in Major
      Depressive Disorder (MDD) patients stems from a breakdown in proactive control,
      and/or anomalies in reactive cognitive control. In our study, MDD patients
      specifically showed increased response latencies when actively inhibiting a
      dominant response to a sad compared with a happy face. This condition was
      associated with a longer duration of a dominant ERP topography (800-900 ms
      poststimulus onset) and a stronger activity in the bilateral dorsal anterior
      cingulate cortex, reflecting abnormal reactive control when inhibiting attention
      to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive
      cognitive control when preparing for the upcoming imperative stimulus (abnormal
      modulation of the contingent negative variation component), accompanied by more
      activity in brain regions belonging to the default mode network. All together,
      deficits to inhibit attention to negative information in MDD might originate from
      an abnormal use of both proactive resources and reactive control processes.

PMID- 24661162
TI  - Neural markers of positive reappraisal and their associations with trait
      reappraisal and worry.
AB  - Positively reinterpreting negative experiences is important for psychological
      well-being and represents a key mechanism of cognitive-behavioral therapies for
      emotional problems. Yet, little is known about the neural mechanisms that
      underlie this process and how they relate to clinically relevant individual
      differences. Here we demonstrate using event-related potentials (ERPs) that
      positively reappraising distress-inducing images is associated with early
      increases in frontal control activity and later decreases in parietal arousal
      related activity. Moreover, we show that people's chronic tendencies to
      reappraise versus worry modulate neural activity in opposing directions--trait
      reappraisal predicts decreases in parietal arousal-related activity during
      positive reappraisal implementation whereas worry predicts increases in the same
      waveform. These findings provide novel insights into the neural time course of
      positive reappraisal. They also speak to the potential clinical utility of
      neurophysiological measures as relatively inexpensive, noninvasive biomarkers
      that could serve as risk indicators and treatment mediators.

PMID- 24661163
TI  - Child temperament and parental depression predict cortisol reactivity to stress
      in middle childhood.
AB  - Children's cortisol reactivity to stress is an important mediator of depression
      risk, making the search for predictors of such reactivity an important goal for
      psychopathologists. Multiple studies have linked maternal depression and
      childhood behavioral inhibition (BI) independently to child cortisol reactivity,
      yet few have tested multivariate models of these risks. Further, paternal
      depression and other child temperament traits, such as positive emotionality
      (PE), have been largely ignored despite their potential relevance. We therefore
      examined longitudinal associations between child fear/BI and PE and parental
      depression, and children's cortisol stress reactivity, in 205 7-year-olds.
      Paternal depression and child fear/BI predicted greater cortisol stress
      reactivity at a follow-up of 164 9-year-olds, and maternal depression and child
      PE interacted to predict children's cortisol reactivity, such that higher child
      PE predicted lower cortisol reactivity in the context of maternal depression.
      Results highlight the importance of both parents' depression, as well as multiple
      facets of child temperament, in developing more comprehensive models of childhood
      cortisol reactivity to stress.

PMID- 24661164
TI  - Characterizing subjective responses to alcohol among adolescent problem drinkers.
AB  - Theoretical models of alcoholism emphasize the acute reinforcing properties of
      alcohol as chief determinants of drinking, and animal research suggests
      adolescents are uniquely sensitive to these effects. Human studies of these
      phenomena, however, are virtually nonexistent. We used ecological momentary
      assessment methods to capture adolescents' subjective responses to alcohol in
      real time in their natural environments. Adolescent participants were 22 problem
      drinkers, ages 15 to 19 years (M = 18.3, SD = 0.09; 55% female; 55% alcohol
      dependent). Participants consumed alcohol on 38% of days during a 1-week
      monitoring period, with an average of 5 drinks per occasion. Momentary data
      revealed that adolescents experience decreased stimulation and increased sedation
      and "high" across the ascending limb of the blood alcohol curve. Notably, greater
      craving predicted higher volumes of subsequent alcohol consumption during the
      episode, whereas greater "high" attenuated use. To test for developmental
      differences in these effects, we pooled these data with data from a similarly
      ascertained sample of 36 adult heavy drinkers, ages 24 to 64 years (M = 38.1, SD
      = 11.8; 50% female; 61% alcohol dependent). Adolescents were more sensitive to
      the stimulant effects of alcohol than adults. This study provides novel data on
      how adolescent problem drinkers experience alcohol in their natural contexts and
      illustrates how these effects, which appear to differ from adult problem
      drinkers, confer liability for future drinking.

PMID- 24661165
TI  - Effects of ALDH2*2 on alcohol problem trajectories of Asian American college
      students.
AB  - The variant aldehyde dehydrogenase allele, ALDH2*2, consistently has been
      associated with protection against alcohol dependence, but the mechanism
      underlying this process is not known. This study examined growth trajectories of
      alcohol consumption (frequency, average quantity, binge drinking, maximum drinks)
      and problems over the college years and then tested whether the ALDH2 genotype
      mediated or moderated the relationship between alcohol consumption and problems.
      Asian American college students (N = 433) reported on their drinking behavior in
      their first year of college and then annually for 3 consecutive years. Alcohol
      consumption and problems increased over the college years for both those with and
      without ALDH2*2, but having an ALDH2*2 allele was associated with less of an
      increase in problems over time. A mediation model was supported, with ALDH2*2
      group differences in problems fully accounted for by differences in frequency of
      binge drinking. Findings also supported a moderation hypothesis: All four alcohol
      consumption variables were significant predictors of subsequent alcohol problems,
      but these relationships were not as strong in those with ALDH2*2 as in those
      without ALDH2*2. Our findings suggest that the interplay between ALDH2*2 and
      drinking-related problems is complex, involving both mediation and moderation
      processes that reduce the likelihood of developing problems via reduction of
      heavy drinking as well as by altering the relationship between alcohol
      consumption and problems. Results of this longitudinal study provide evidence
      that what seems like a relatively straightforward effect of a diminished ability
      to metabolize alcohol on drinking behavior is actually dependent on behavior and
      developmental stage.

PMID- 24661166
TI  - Longitudinal test of a developmental model of the transition to early drinking.
AB  - This article reports on a longitudinal test of a developmental model of early
      drinking that specifies transactions among personality, learning, and behavior in
      the risk process. The model was tested on 1,906 children making the transition
      from elementary school to middle school across 3 time points: the spring of 5th
      grade, the fall of 6th grade, and the spring of 6th grade. In a transaction that
      has been referred to as acquired preparedness, individual differences in the
      trait positive urgency at the end of 5th grade were associated with increases in
      expectancies for social facilitation from alcohol at the start of 6th grade,
      which then predicted drinker status at the end of 6th grade. In addition, the
      alcohol expectancy and drinker status predicted each other reciprocally across
      time. Multiple factors appear to transact to predict early drinking behavior.

PMID- 24661168
TI  - An intact threat superiority effect for nonsocial but not social stimuli in
      schizophrenia.
AB  - Studies examining the processing of threat-related information in schizophrenia
      suggest that patients may show intact abilities to detect nonsocial threats
      despite impaired processing of social threat. The present study examined
      potential differences between social and nonsocial threat detection abilities in
      schizophrenia via two analogous threat perception tasks: one that used nonsocial
      threat (i.e., snakes) and one that used social threat (i.e., angry faces). Both
      tasks have reliably demonstrated a threat superiority effect (TSE) among healthy
      individuals in which threat-related stimuli are detected more accurately and
      efficiently than non-threat-related stimuli. Results from 30 healthy controls and
      35 individuals with schizophrenia indicated that control participants showed a
      normative TSE on both the nonsocial and social tasks. In contrast, patients
      showed a TSE on only the nonsocial task, demonstrating intact detection abilities
      for nonsocial threat but impaired detection of social threats. The discrepant
      performance across nonsocial and social threat detection tasks within the patient
      group is consistent with evidence indicating that social and nonsocial
      information processing can be differentially affected in schizophrenia.

PMID- 24661167
TI  - Give me just a little more time: effects of alcohol on the failure and recovery
      of cognitive control.
AB  - Numerous externalizing behaviors, from aggression to risk taking to drug abuse,
      stem from impaired cognitive control, including that brought about by the acute
      effects of alcohol. Although research generally indicates that alcohol impairs
      cognitive abilities, a close examination of the literature suggests that
      alcohol's effects are quite variable and likely depend on a number of contextual
      factors. The purpose of the current study was to characterize the effects of
      alcohol on cognitive control in terms of neural and behavioral responses to
      successful and unsuccessful control attempts. Participants were randomly assigned
      to consume an alcohol (0.80 g/kg ETOH), placebo, or nonalcoholic control beverage
      prior to completing a cognitive control (flanker) task while event-related brain
      potentials were recorded. Alcohol reduced the amplitude of the error-related
      negativity on error trials and increased the posterror compatibility effect in
      response time. Of particular interest, neural indices of conflict monitoring and
      performance adjustment (frontal slow wave) were attenuated by alcohol, but only
      on trials following errors. These functions had recovered, however, by 2 trials
      after an error. These findings suggest that alcohol's effects on cognitive
      control are best characterized as impaired (or delayed) recovery following
      control failures. Implications of these findings for understanding alcohol's
      effects on behavioral undercontrol are discussed.

PMID- 24661169
TI  - Event-related theta synchronization predicts deficit in facial affect recognition
      in schizophrenia.
AB  - Growing evidence suggests that abnormalities in the synchronized oscillatory
      activity of neurons in schizophrenia may lead to impaired neural activation and
      temporal coding and thus lead to neurocognitive dysfunctions, such as deficits in
      facial affect recognition. To gain an insight into the neurobiological processes
      linked to facial affect recognition, we investigated both induced and evoked
      oscillatory activity by calculating the Event Related Spectral Perturbation
      (ERSP) and the Inter Trial Coherence (ITC) during facial affect recognition.
      Fearful and neutral faces as well as nonface patches were presented to 24
      patients with schizophrenia and 24 matched healthy controls while EEG was
      recorded. The participants' task was to recognize facial expressions. Because
      previous findings with healthy controls showed that facial feature decoding was
      associated primarily with oscillatory activity in the theta band, we analyzed
      ERSP and ITC in this frequency band in the time interval of 140-200 ms, which
      corresponds to the N170 component. Event-related theta activity and phase-locking
      to facial expressions, but not to nonface patches, predicted emotion recognition
      performance in both controls and patients. Event-related changes in theta
      amplitude and phase-locking were found to be significantly weaker in patients
      compared with healthy controls, which is in line with previous investigations
      showing decreased neural synchronization in the low frequency bands in patients
      with schizophrenia. Neural synchrony is thought to underlie distributed
      information processing. Our results indicate a less effective functioning in the
      recognition process of facial features, which may contribute to a less effective
      social cognition in schizophrenia.

PMID- 24661170
TI  - Neural activity to positive expressions predicts daily experience of
      schizophrenia-spectrum symptoms in adults with high social anhedonia.
AB  - Social anhedonia (SA), the diminished pleasure from social relationships, is a
      prominent characteristic of the vulnerability and manifestation of schizophrenia
      disorder. However, SA can develop for multiple reasons and little is known about
      its neural basis; these 2 issues hinder the utility and sensitivity of SA as a
      marker of schizophrenia pathology. This study investigated whether lateral
      prefrontal cortex (LPFC) deficits in social reward processing are associated with
      both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI),
      a community sample of healthy adults (N = 30) with high and low SA viewed
      positive, negative, and neutral facial expressions. Afterward, participants
      completed an online daily diary in which they rated schizophrenia-spectrum
      symptoms and occurrence of interpersonal conflict each day for 21 days. Compared
      with low SA, high SA participants had less ventral (V)LPFC activity to positive
      versus neutral expressions. In addition, participants with a combination of high
      SA and low VLPFC activity to positive versus neutral expressions had worse daily
      diary ratings of schizophrenia-spectrum symptoms, including worse cognition,
      paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor
      activation). Finally, among high SA participants, VLPFC activity predicted the
      daily relationship between distress from interpersonal conflict and symptom
      severity; specifically, high SA participants with low VLPFC activity had worse
      paranoia on days of high conflict distress. These findings indicate that VLPFC
      deficits in positive emotion are associated with both SA and other schizophrenia
      spectrum symptoms and that understanding the interaction of SA, VLPFC function,
      and social stress could facilitate the use of SA in the prevention and treatment
      of schizophrenia.

PMID- 24661171
TI  - Amygdala reactivity and negative emotionality: divergent correlates of antisocial
      personality and psychopathy traits in a community sample.
AB  - Previous studies have emphasized that antisocial personality disorder (APD) and
      psychopathy overlap highly but differ critically in several features, notably
      negative emotionality (NEM) and possibly amygdala reactivity to social signals of
      threat and distress. Here we examined whether dimensions of psychopathy and APD
      correlate differentially with NEM and amygdala reactivity to emotional faces.
      Testing these relationships among healthy individuals, dimensions of psychopathy
      and APD were generated by the profile matching technique of Lynam and Widiger
      (2001), using facet scales of the NEO Personality Inventory-Revised, and amygdala
      reactivity was measured using a well-established emotional faces task, in a
      community sample of 103 men and women. Higher psychopathy scores were associated
      with lower NEM and lower amygdala reactivity, whereas higher APD scores were
      related to greater NEM and greater amygdala reactivity, but only after
      overlapping variance in APD and psychopathy was adjusted for in the statistical
      model. Amygdala reactivity did not mediate the relationship of APD and
      psychopathy scores to NEM. Supplemental analyses also compared other measures of
      factors within psychopathy in predicting NEM and amygdala reactivity and found
      that Factor 2 psychopathy was positively related to NEM and amygdala reactivity
      across measures of psychopathy. The overall findings replicate seminal
      observations on NEM in psychopathy by Hicks and Patrick (2006) and extend this
      work to neuroimaging in a normative population. They also suggest that one
      critical way in which APD and psychopathy dimensions may differ in their etiology
      is through their opposing levels of NEM and amygdala reactivity to threat.

PMID- 24661172
TI  - The relative impact of socioeconomic status and childhood trauma on Black-White
      differences in paranoid personality disorder symptoms.
AB  - The current study examines mechanisms of racial differences in symptoms of
      paranoid personality disorder (PPD) in a sample of adults ages 55-64 from the St.
      Louis, MO area. Socioeconomic status (SES) and childhood trauma were tested as
      intervening variables in the association between race and PPD symptoms using
      structural equation modeling. PPD symptoms were modeled as a latent variable
      composed of items from the PPD scales of the Multi-Source Assessment of
      Personality Pathology self and informant reports and the Structured Interview for
      the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM
      IV) Personality. Childhood trauma was measured using the Traumatic Life Events
      Questionnaire, and SES was a composite of parent education, participant
      education, and annual household income. Blacks exhibited higher levels of PPD
      symptoms across the 3 personality measures, reported significantly lower SES, and
      reported greater childhood trauma. The proposed model was a good fit to the data,
      and the effect of race on PPD symptoms operated mainly through SES. The indirect
      effect through SES was stronger for males. Findings suggest that racial
      differences in PPD symptoms are partly explained by problems more commonly
      experienced by Black individuals.

PMID- 24661173
TI  - An investigation of differential item functioning across gender of BPD criteria.
AB  - Gender differences in prevalence rates of Borderline Personality Disorder (BPD)
      may reflect true differences between groups or may reflect some form of gender
      bias in diagnostic criteria. The detection of differential item functioning (DIF)
      using item response theory methods provides a powerful method of evaluating
      whether gender differences in prevalence rates of BPD reflect true mean
      differences or criterion bias. The aim of the current study was to evaluate
      gender-based DIF in DSM BPD criteria. The Structured Clinical Interview for
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)
      Axis II Personality Disorders (SCID-II: First, Spitzer, Gibbon, Williams, &
      Benjamin, 1994) was administered to 747 adult inpatients. Results indicated DIF
      for 2 BPD criteria (impulsivity and uncontrolled anger), such that it was easier
      for these items to be endorsed for men compared with women at the same level of
      latent trait. At the level of the test, men were expected to be rated slightly
      higher than women on the SCID-II at the same level of latent BPD liability.
      Implications of these results for research and clinical assessment are discussed.

PMID- 24661174
TI  - Drinking motives moderate daily relationships between PTSD symptoms and alcohol
      use.
AB  - Posttraumatic stress disorder (PTSD) and alcohol dependence (AD) frequently co
      occur, although results of both cross-sectional and longitudinal studies
      evaluating the nature of their relationship have been mixed. There has been
      varied support for competing models explaining how these conditions influence one
      another. To assess both the self-medication and mutual maintenance models, as
      well as examine the potential moderating role of drinking motives, the current
      study used Generalized Estimating Equations to evaluate daily associations for an
      average of 7.3 days between PTSD symptoms and alcohol use in a mixed-gender
      sample of individuals who met criteria for both PTSD and AD. Results generally
      supported a self-medication model with elevated PTSD symptoms predictive of
      greater alcohol use on that same day and on the following day. Contrary to a
      mutual maintenance model prediction, drinking did not predict next-day PTSD
      symptoms. Results also indicated that both coping and enhancement drinking
      motives were significant moderators of the PTSD and drinking relationships,
      suggesting that these relationships may be more or less salient depending on an
      individual's particular drinking motivations. For example, among those higher on
      coping drinking motives, a 1-unit increase in PTSD symptom severity was
      associated with a 35% increase in amount of alcohol consumed the same day, while
      among those low on coping drinking motives, a 1-unit PTSD increase was associated
      with only a 10% increase in alcohol consumption. We discuss implications of these
      findings for the larger literature on the associations between PTSD and alcohol
      use as well as for clinical interventions. (PsycINFO Database Record (c) 2014
      APA, all rights reserved). 

PMID- 24661175
TI  - Spatial working memory in children with high-functioning autism: intact
      configural processing but impaired capacity.
AB  - Visual attention and visual working memory exert severe capacity limitations on
      cognitive processing. Impairments in both functions may exacerbate the social and
      communication deficits seen in children with an autism spectrum disorder (ASD).
      This study characterizes spatial working memory and visual attention in school
      age children with high-functioning autism. Children with ASD, and age, gender,
      and IQ-matched typically developing (TD) children performed 2 tasks: a spatial
      working memory task and an attentive tracking task. Compared with TD children,
      children with ASD showed a more pronounced deficit in the spatial working memory
      task than the attentive tracking task, even though the latter placed significant
      demands on sustained attention, location updating, and distractor inhibition.
      Because both groups of children were sensitive to configuration mismatches
      between the sample and test arrays, the spatial working memory deficit was not
      because of atypical organization of spatial working memory. These findings show
      that attention and working memory are dissociable, and that children with ASD
      show a specific deficit in buffering visual information across temporal
      discontinuity.

PMID- 24661177
TI  - Understanding processing speed weaknesses among pedophilic child molesters:
      response style vs. neuropathology.
AB  - Research shows that pedophilic (PED) child molesters exhibit slower performance
      speed and greater performance accuracy when compared to nonpedophilic (N-PED)
      child molesters or other criminal and noncriminal controls. The purpose of the
      present study was to examine whether these differences reflect a slow/deliberate
      response style among PEDS (as we have previously hypothesized; Eastvold, Suchy, &
      Strassberg, 2011; Suchy, Whittaker, Strassberg, & Eastvold, 2009a, 2009b), or a
      fundamental neuropathological weakness in processing speed. Data came from a
      larger study examining neurocognition among sex offenders. Processing speed in
      three different domains (motor speed, visual-perceptual speed, and visual-motor
      integration) was examined in 20 phallometrically identified PEDs, 20 N-PEDs, and
      20 nonsexual offenders, using both clinical (Finger Tapping, Symbol Search, Digit
      Symbol Coding) and experimental measures (Inspection Time Task [ITT]). The ITT
      assessed speed of visual-perceptual processing independent of response speed. On
      clinical measures, PEDs exhibited slower visual perception [F(2, 57) = 5.24, p =
      .008] and visual-motor integration [F(2, 57) = 5.02, p = .010] than the other
      groups, with no differences for simple motor speed. On the ITT, PEDs performed
      less accurately than the other groups [F(2, 57) = 3.95, p = .025], clearly
      indicating that slow processing speed cannot be explained by a deliberate
      response style. Group differences persisted after controlling for other potential
      confounds (age, estimate IQ, working memory, ethnicity, and substance use). PEDs'
      slower performance is due to a fundamental neurocognitive weakness, rather than a
      slow/deliberate response style. These results are consistent with Cantor et al.'s
      (2008) work identifying white matter abnormalities among PEDs and provide further
      support for a neurodevelopmental etiology of pedophilia.

PMID- 24661176
TI  - Specificity of affective instability in patients with borderline personality
      disorder compared to posttraumatic stress disorder, bulimia nervosa, and healthy
      controls.
AB  - Affective instability is a core feature of borderline personality disorder (BPD).
      The use of advanced assessment methodologies and appropriate statistical analyses
      has led to consistent findings that indicate a heightened instability in patients
      with BPD compared with healthy controls. However, few studies have investigated
      the specificity of affective instability among patients with BPD with regard to
      relevant clinical control groups. In this study, 43 patients with BPD, 28
      patients with posttraumatic stress disorder (PTSD), 20 patients with bulimia
      nervosa (BN), and 28 healthy controls carried e-diaries for 24 hours and were
      prompted to rate their momentary affective states approximately every 15 minutes
      while awake. To quantify instability, we used 3 state-of-the-art indices:
      multilevel models for squared successive differences (SSDs), multilevel models
      for probability of acute changes (PACs), and aggregated point-by-point changes
      (APPCs). Patients with BPD displayed heightened affective instability for
      emotional valence and distress compared with healthy controls, regardless of the
      specific instability indices. These results directly replicate earlier studies.
      However, affective instability did not seem to be specific to patients with BPD.
      With regard to SSDs, PACs, and APPCs, patients with PTSD or BN showed a similar
      heightened instability of affect (emotional valence and distress) to that of
      patients with BPD. Our results give raise to the discussion if affective
      instability is a transdiagnostic or a disorder-specific mechanism. Current
      evidence cannot answer this question, but investigating psychopathological
      mechanisms in everyday life across disorders is a promising approach to enhance
      validity and specificity of mental health diagnoses.

PMID- 24661178
TI  - Antibacterial enzymes from the functional screening of metagenomic libraries
      hosted in Ralstonia metallidurans.
AB  - Phenotype-based screening of bacterial metagenomic libraries provides an avenue
      for the discovery of novel genes, enzymes, and metabolites that have a variety of
      potential clinical and industrial uses. Here, we report the identification of a
      functionally diverse collection of antibacterially active enzymes from the
      phenotypic screening of 700 000 cosmid clones prepared from Arizona soil DNA and
      hosted in Ralstonia metallidurans. Environmental DNA clones surrounded by zones
      of growth inhibition in a bacterial overlay assay were found, through
      bioinformatics and functional analyses, to encode enzymes with predicted
      peptidase, lipase, and glycolytic activities conferring antibiosis. The
      antibacterial activities observed in our R. metallidurans-based assay could not
      be replicated with the same clones in screens using Escherichia coli as a
      heterologous host, suggesting that the large-scale screening of metagenomic
      libraries for antibiosis using phylogenetically diverse hosts should be a
      productive strategy for identifying enzymes with functionally diverse
      antibacterial activities. 

PMID- 24661179
TI  - Mother-embryo isotope (delta15N, delta13C) fractionation and mercury (Hg)
      transfer in aplacental deep-sea sharks.
AB  - Stable carbon (delta13C) and nitrogen (delta15N) isotopic values and total
      mercury (Hg) concentrations were analysed in muscle and liver of mothers and
      embryos of two aplacental shark species, Squalus megalops and Centrophorus
      moluccensis. Embryos of the two species had similar or lower isotopic values than
      their respective mothers, the only exception being for delta13C, which was higher
      in the liver of C. moluccensis embryos than in their mothers. Hg concentrations
      were systematically lower in embryos compared with their mothers suggesting a low
      transfer of this element in muscle and liver.

PMID- 24661180
TI  - Reversal of aggregation using beta-breaker dipeptide containing peptides:
      Application to Abeta(1-40) self-assembly and its inhibition.
AB  - Reversion of protein or peptide aggregation is a formidable task, important in
      various domains of research at the interface of chemistry, medicine, and
      nanoscience. A novel class of dipeptides, termed as beta-breaker dipeptides
      (BBDPs), is identified, which can be incorporated into the self-recognizing
      sequences to generate a novel class of conformational switch which forms beta
      sheet at an initial stage and then converts in a controlled manner to random coil
      at specific conditions. Incorporation of BBDPs in a well designed amyloidogenic
      peptides generates a special class of beta-sheet breaker peptides those undergo a
      chemical change at physiological condition generating a breaker element in situ.
      These beta-breaker peptides are shown to first incorporate into the amyloid and
      then disrupt it. Such conformational switches may be used to study
      agrregation/disaggregation process and may find many biomedical applications
      relevant to aggregation related disorders. Such strategy for reversion of peptide
      aggregation using chemical tricks may find application in material chemistry as
      well.

PMID- 24661181
TI  - Stakeholder engagement in patient-centered outcomes research: high-touch or high
      tech?
AB  - Patient and stakeholder engagement enhances the meaningfulness of patient
      centered outcomes research. Continuous engagement of diverse patients helps to
      achieve representativeness and to avoid tokenism, but is perceived as challenging
      due to resource and time constraints. The widespread availability of the
      internet, mobile phones, and electronic devices makes 'high-tech' solutions
      appealing, but such approaches may trade-off larger sample sizes for shallower
      engagement and/or skewed perspectives if most participants reflect users of
      technology. More traditional 'high-touch' solutions such as in-person interviews,
      focus groups, and town hall meetings can provide qualitative and sociological
      context and potentially more in-depth insights from small numbers of patients,
      but such approaches are also prone to selection bias as well. We compare and
      contrast high-tech and high-touch approaches to engaging stakeholders and suggest
      hybrid processes. 

PMID- 24661182
TI  - Ruthenium tris(2-pyridylmethyl)amine as an effective photocaging group for
      nitriles.
AB  - Ruthenium(II) tris(2-pyridylmethyl)amine (TPA) is an effective caging group for
      nitriles that provides high levels of control over the enzyme activity with
      light. Two caged nitriles were prepared, [Ru(TPA)(MeCN)2](PF6)2 (1) and
      [Ru(TPA)(3)2](PF6)2 (2), where 3 is the cathepsin K inhibitor Cbz-Leu-NHCH2CN,
      and characterized by various spectroscopic techniques and mass spectrometry. Both
      1 and 2 show the release of a single nitrile within 20 min of irradiation with
      365 nm light. Complex 2 acts as a potent, photoactivated inhibitor of human
      cathepsin K. IC50 values were determined for 2 and 3. Enzyme inhibition for 2 was
      enhanced by a factor of 89 upon exposure to light, with IC50 values of 63 nM
      (light) and 5.6 MUM (dark). 

PMID- 24661183
TI  - Inhibition of the purinergic pathway prolongs mouse lung allograft survival.
AB  - Lung transplantation has limited survival with current immunosuppression. ATP is
      released from activated T cells, which act as costimulatory molecules through
      binding to the purinergic receptor P2XR7. We investigated the role of blocking
      the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP
      (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants
      were performed using mice with major histocompatibility complex mismatch, BALB/c
      to C57BL6. Recipients received suramin or oATP, and lung allografts were
      evaluated 15 to >= 60 days after transplantation. Recipients were also treated
      with oATP after the onset of moderate to severe rejection to determine its
      ability to rescue lung allografts. Outcomes measures included lung function,
      histology, thoracic imaging, and allo-immune responses. Blocking purinergic
      receptors with the nonselective inhibitor suramin or with the P2XR7-selective
      inhibitor oATP reduced acute rejection and prolonged lung allograft survival for
      >= 60 days with no progression in severity. There were fewer inflammatory cells
      within lung allografts, less rejection, and improved lung function, which was
      maintained over time. CD4 and CD8 T cells were reduced within lung allografts
      with impaired activation with prolonged impairment of CD8 responses. In vitro,
      oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-gamma and TNF-alpha
      and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents,
      cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP
      alone resulted in better outcomes than cyclosporine alone. This study illustrates
      a potential new pathway to target in hopes of prolonging survival of lung
      transplant recipients. 

PMID- 24661184
TI  - An investigation of DIF mechanisms in the context of differential testlet
      effects.
AB  - This study investigated differential item functioning (DIF) mechanisms in the
      context of differential testlet effects across subgroups. Specifically, we
      investigated DIF manifestations when the stochastic ordering assumption on the
      nuisance dimension in a testlet does not hold. DIF hypotheses were formulated
      analytically using a parametric marginal item response function approach and
      compared with empirical DIF results from a unidimensional item response theory
      approach. The comparisons were made in terms of type of DIF (uniform or non
      uniform) and direction (whether the focal or reference group was advantaged). In
      general, the DIF hypotheses were supported by the empirical results, showing the
      usefulness of the parametric approach in explaining DIF mechanisms. Both
      analytical predictions of DIF and the empirical results provide insights into
      conditions where a particular type of DIF becomes dominant in a specific DIF
      direction, which is useful for the study of DIF causes. 

PMID- 24661185
TI  - Enhancing gas chromatography-time of flight mass spectrometry data analysis using
      two-dimensional mass channel cluster plots.
AB  - A novel data reduction and representation method for gas chromatography time-of
      flight mass spectrometry (GC-TOFMS) is presented that significantly facilitates
      separation visualization and analyte peak deconvolution. The method utilizes the
      rapid mass spectral data collection rate (100 scans/s or greater) of current
      generation TOFMS detectors. Chromatographic peak maxima (serving as the retention
      time, tR) above a user specified signal threshold are located, and the
      chromatographic peak width, W, are determined on a per mass channel (m/z) basis
      for each analyte peak. The peak W (per m/z) is then plotted against its
      respective tR (with 10 ms precision) in a two-dimensional (2D) format, producing
      a cluster of points (i.e., one point per peak W versus tR in the 2D plot).
      Analysis of GC-TOFMS data by this method produces what is referred to as a two
      dimensional mass channel cluster plot (2D m/z cluster plot). We observed that
      adjacent eluting (even coeluting) peaks in a temperature programmed separation
      can have their peak W vary as much as ~10-15%. Hence, the peak W provides useful
      chemical selectivity when viewed in the 2D m/z cluster plot format. Pairs of
      overlapped analyte peaks with one-dimensional GC resolution as low as Rs ~ 0.03
      can be visually identified as fully resolved in a 2D m/z cluster plot and readily
      deconvoluted using chemometrics (i.e., demonstrated using classical least-squares
      analysis). Using the 2D m/z cluster plot method, the effective peak capacity of
      one-dimensional GC separations is magnified nearly 40-fold in one-dimensional GC,
      and potentially ~100-fold in the context of comparing it to a two-dimensional
      separation. The method was studied using a 73 component test mixture separated on
      a 30 m * 250 MUm i.d. RTX-5 column with a LECO Pegasus III TOFMS. 

PMID- 24661186
TI  - Gynogenetic activation of porcine oocytes.
AB  - The possibility of fertilization without male contribution to the embryonic
      genome was investigated in pig oocytes. Mature oocytes were co-incubated with
      sperm, and in an attempt to prevent the incorporation of the sperm head into the
      ooplasm, the actin polymerization inhibitor cytochalasin B was added to the
      fertilization medium. We found that perturbing actin filament integrity did not
      affect the pattern of the sperm-induced Ca(2+) signal or the process of cortical
      granule exocytosis, and it did not alter the percentage of activated oocytes
      compared to the control (oocytes fertilized in the absence of the inhibitor).
      However, over 20% of the cytochalasin B-treated oocytes formed only a single
      pronucleus after fertilization, indicating that the inhibitor blocked sperm head
      incorporation at least in some oocytes. In most cases, cytochalasin B also
      prevented the integration of the male chromosomes into the embryonic genome as
      determined by the absence of the SRY gene in the embryonic blastomeres or by the
      frequency of embryos showing green fluorescence after sperm from a GFP-transgenic
      boar was used for fertilization. Finally, the percentage of embryos that
      developed beyond the four-cell stage and the total number of nuclei in the
      resultant blastocysts were higher when oocytes reconstructed by nuclear transfer
      were activated by fertilization in the presence of cytochalasin B compared to the
      control group, where activation was induced by electroporation. These results
      suggest that fertilization in the presence of cytochalasin B can induce oocyte
      activation while it also prevents integration of the male genome into the embryo.
      This method has the potential to be used as an alternative to inducing embryonic
      development after nuclear transfer.

PMID- 24661187
TI  - Therapeutic potential of adipose stem cells in tissue repair of irradiated
      skeletal muscle in a rabbit model.
AB  - The repairing function and differentiation potency of adipose stem cells (ASCs)
      transplantation following skeletal muscle injury induced by radiotherapy are
      still not well defined. In this study, one side of the buttocks of 64 New Zealand
      white rabbits underwent irradiation and were randomly divided into an ASCs group
      [5*10(7) ASCs labeled with CM-Dil and suspended in 1 mL of phosphate-buffered
      saline (PBS), via intramuscular injection] and a PBS group (1 mL of PBS, via
      intramuascular injection). ASCs were isolated in New Zealand white rabbits in
      vitro, and migration of ASCs labeled with CM-Dil was observed after
      transplantation in vivo. A significant decrease of histological severity scoring
      was found in irradiated tissue obtained in the ASCs group compared with that in
      PBS group. Additionally, compensatory hyperplasia was noted after ASCs
      transplantation in the injured tissues. Moreover, ASCs could upregulate the
      expression of vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF) and promote the angiogenesis of the injured tissues.
      Interestingly, myofilament-like structures were identified in irradiated muscle
      cells after ASCs transplantation. We concluded that ASCs transplantation could
      repair the radiation-induced skeletal muscle injury. Its mechanism may be, at
      least partly, associated with the upregulation of VEGF and bFGF, angiogenesis,
      promoting the compensatory hyperplasia of muscle satellite cells, as well as the
      myogenic differentiation.

PMID- 24661188
TI  - Al-Akhawayni and the early descriptions of meningitis.
AB  - Abubakr Rabi-ibn Ahmad Akhawayni Bukhari, also known as Al-Akhawayni, was a
      Persian physician who lived in the Near East during an age in which medical
      knowledge blossomed in the Islamic world. This era, the "Islamic Golden Age,"
      extended from the tenth to the twelfth centuries AD. During his lifetime as a
      physician, Al-Akhawayni was famous for his expertise in medicine, including
      disorders that would be considered neurological today. In his extant book Hidayat
      al-Muta'allemin fi al-Tibb [A Scholar's Guide to Medicine], he provided an early
      description of what is probably meningitis. He illustrated the membranes
      surrounding the brain tissue in detail and described manifestations resulting
      from their inflammation. 

PMID- 24661190
TI  - Cs2CO3-promoted one-pot synthesis of alkynylphosphonates, -phosphinates, and 
      phosphine oxides.
AB  - A novel and efficient Cs2CO3-promoted phosphorylation or phosphinylation of
      various 1,1-dibromo-1-alkenes with readily available trialkyl phosphites, ethyl
      diphenylphosphinite, or diethyl phenylphosphonite has been developed under metal
      free conditions, providing a practical and powerful tool for one-pot synthesis of
      valuable alkynylphosphonates, -phosphinates, and -phosphine oxides in good to
      excellent yields.

PMID- 24661189
TI  - Immunoreactivity to food antigens in patients with chronic urticaria.
AB  - The goal of study was better understanding of complex immune mechanisms that can
      help to evaluate patients with chronic urticaria (CU), especially those with
      unknown etiology. The study involved 55 patients with CU. Control group consisted
      of up to 90 healthy persons. The presence and intensity of serum IgG, IgA, IgM
      and IgE antibodies to common food antigens: cow's milk proteins (CMP), gliadin
      and phytohemagglutinin were determined by ELISA. Determination of subpopulations
      of immunocompetent cells was performed by flow cytometry. Significantly enhanced
      IgE, but also IgA immunity to CMP was found in patients with CU in comparison to
      healthy controls: (p < 0.000004) and (p < 0.002), respectively. Notably, in 40
      out of 55 CU patients, the increased levels of some type of immunoglobulin
      reactivity to CMP were found. Regarding gliadin, only the levels of serum IgE
      anti-gliadin antibodies were significantly enhanced in patients with CU (p <
      0.04). Significantly enhanced percentage of CD89+ cells accompanied with
      significantly lower percentage of lymphocytes and significantly higher mean
      fluorescence intensity of CD26 expression on lymphocytes were found in patients
      with CU in comparison to healthy controls (p < 0.04), (p < 0.02) and (p < 0.003),
      respectively. Results of this study may help in better understanding the complex
      immune disturbances in patients with CU.

PMID- 24661191
TI  - Liver injury possibly related to drug interaction after liver transplant: a case
      report.
AB  - WHAT IS KNOWN AND OBJECTIVE: Drug-induced hepatotoxicity is potentially lethal.
      Liver transplant patients receive a large number of medications and adverse drug
      reactions, and drug-drug interactions must be closely monitored. CASE SUMMARY: We
      report a case of a 29-year-old liver transplant patient who suffered liver injury
      most likely induced by drug interaction between capecitabine and warfarin.
      Vitamin K1 caused skin rash possibly because of the distribution and metabolism
      characteristic of the drug in this patient. WHAT IS NEW AND CONCLUSION: Close
      monitoring and prompt discontinuation of the drugs with high volume of
      distribution and metabolized through the liver are necessary to avoid drug-drug
      interaction in liver transplant patients.

PMID- 24661192
TI  - Review of deprescribing processes and development of an evidence-based, patient
      centred deprescribing process.
AB  - Inappropriate use of medication is widespread, especially in older people, and is
      associated with risks, including adverse drug reactions, hospitalization and
      increased mortality. Optimization of appropriate medication use to minimize these
      harms is an ongoing challenge in healthcare. The term 'deprescribing' has been
      used to describe the complex process that is required for safe and effective
      cessation of medication. Patients play an important role in their own health and,
      while they may complain about the number of medications they have to take, they
      may also be reluctant to cease a medication when given the opportunity to do so.
      A review of previously proposed deprescribing processes and relevant literature
      was used to develop the patient-centred deprescribing process, which is a five
      step cycle that encompasses gaining a comprehensive medication history,
      identifying potentially inappropriate medications, determining whether the
      potentially inappropriate medication can be ceased, planning the withdrawal
      regimen (e.g. tapering where necessary) and provision of monitoring, support and
      documentation. This is the first deprescribing process developed using knowledge
      of the patients' views of medication cessation; it focuses on engaging patients
      throughout the process, with the aim of improving long-term health outcomes.
      Despite a comprehensive review of the literature, there is still a lack in the
      evidence base on which to conduct deprescribing. The next step in broadening the
      evidence to support deprescribing will be to test the developed process to
      determine feasibility in the clinical setting. 

PMID- 24661193
TI  - Role of male pelvic floor muscles and anterior fibromuscular stroma in males on
      alpha(1)-blocker treatment: a magnetic resonance imaging study.
AB  - Dynamic motion of the pelvic floor muscles during voiding was analyzed using real
      time magnetic resonance imaging. To evaluate the contraction of the pelvic floor
      muscles, striated urethral sphincter distance, levator ani muscle thickness and
      anterior fibromuscular stroma distance were measured. The percent contraction of
      the striated urethral sphincter from before voiding to just before initiation of
      voiding was 14% in the normal group and 5% in the voiding dysfunction group. The
      percent contraction of the anterior fibromuscular stroma from before voiding to
      just before initiation of voiding was 11% in the normal group and 1% in the
      voiding dysfunction group; the percent contraction of the muscles was
      significantly greater in the normal group (P < 0.05). Striated urethral sphincter
      and anterior fibromuscular stroma contraction at initiation of voiding open the
      bladder neck and urethra. This plays an important role in the smooth initiation
      of voiding. 

PMID- 24661194
TI  - Shape-selective deposition and assembly of anisotropic nanoparticles.
AB  - We report the large-area assembly of anisotropic gold nanoparticles into
      lithographically defined templates with control over their angular position using
      a capillary force-based approach. We elucidate the role of the geometry of the
      templates in the assembly of anisotropic nanoparticles consisting of different
      shapes and sizes. These insights allow us to design templates that immobilize
      individual triangular nanoprisms and concave nanocubes in a shape-selective
      manner and filter undesired impurity particles from a mixture of triangular
      prisms and other polyhedra. Furthermore, by studying the assembly of two
      particles in the same template, we elucidate the importance of interparticle
      forces in this method. These advances allow for the construction of face-to-face
      and edge-to-edge nanocube dimers as well as triangular nanoprism bowtie antennas.
      As an example of the fundamental studies enabled by this assembly method, we
      investigate the surface-enhanced Raman scattering (SERS) of face-to-face concave
      cube dimers both experimentally and computationally and reveal a strong
      polarization dependence of the local field enhancement. 

PMID- 24661195
TI  - Engineering a new generation of hemostatic agents: highlights of the Scientific
      Session on Hemostasis at the 2013 meeting of the American Society of Hematology.

PMID- 24661196
TI  - Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a
      high altitude trek to everest base cAMP.
AB  - Exposure to high altitude is associated with sustained, but reversible, changes
      in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst
      the underlying mechanisms remain elusive, tissue hypoxia increases generation of
      reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF)
      transcription factors, bringing about transcriptional changes that suppress
      oxidative phosphorylation and activate autophagy. We therefore investigated
      whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the
      cardiac perturbations associated with altitude exposure. Twenty-three volunteers
      (10 male, 13 female, 46+/-3 years) were recruited from the 2009 Caudwell Xtreme
      Everest Research Treks and studied before, and within 48 h of return from, a 17
      day trek to Everest Base Camp, with subjects receiving either no intervention
      (controls) or 300 mg Coenzyme Q10 per day throughout altitude exposure. Cardiac
      magnetic resonance imaging and echocardiography were used to assess cardiac
      morphology and function. Following altitude exposure, body mass fell by 3 kg in
      all subjects (p<0.001), associated with a loss of body fat and a fall in BMI.
      Post-trek, left ventricular mass had decreased by 11% in controls (p<0.05) and by
      16% in Coenzyme Q10-treated subjects (p<0.001), whereas mitral inflow E/A had
      decreased by 18% in controls (p<0.05) and by 21% in Coenzyme Q10-treated subjects
      (p<0.05). Coenzyme Q10 supplementation did not, therefore, prevent the loss of
      left ventricular mass or change in diastolic function that occurred following a
      trek to Everest Base Camp.

PMID- 24661197
TI  - Silica and double-stranded RNA synergistically induce bronchial epithelial
      apoptosis and airway inflammation.
AB  - Silica crystals (silica), which are the main mineral component of volcanic ash
      and desert dust, can activate the caspase-1-activating inflammasome in phagocytic
      cells to secrete IL-1beta. Although inhalation of silica-containing dust is known
      to exacerbate chronic respiratory diseases, probably through inflammasome
      activation, its direct effects on bronchial epithelial cells remain unclear.
      Here, we show that silica and double-stranded RNA (dsRNA) synergistically induces
      caspase-9-dependent apoptosis, but not inflammasome activation, of bronchial
      epithelial cells. Intranasal administration of silica and dsRNA to mice
      synergistically enhanced neutrophil infiltration in the airway without IL-1beta
      release in the bronchoalveolar lavage fluid. Histopathological analysis revealed
      that silica or dsRNA alone induced slight airway inflammation, whereas combined
      administration significantly enhanced airway inflammation and epithelial damage.
      These novel findings suggest that inhalation of silica-containing dust may cause
      inflammasome-independent airway inflammation, possibly by damaging the epithelial
      barrier, especially at the time of viral infection. These responses may also be
      involved in acute lung injury caused by inhaled silica-containing dust. 

PMID- 24661198
TI  - Genome size and genomic GC content evolution in the miniature genome-sized family
      Lentibulariaceae.

PMID- 24661199
TI  - Incidence of Legionella and heterotrophic bacteria in household rainwater tanks
      in Azumino, Nagano prefecture, Japan.
AB  - Many administrative agencies in Japan are encouraging installation of household
      rainwater-storage tanks for more effective use of natural rainwater. Water
      samples were collected periodically from 43 rainwater tanks from 40 households
      and tested for the presence of Legionella species and the extent of heterotrophic
      bacteria in Azumino city, Nagano prefecture, Japan. PCR assays indicated the
      presence of Legionella spp. in 12 (30%) of the 43 tank water samples. Attempts
      were made to identify correlations between PCR positive samples, topography, pH,
      chemical oxygen demand (COD), atmospheric temperature and the numbers of
      heterotrophic bacteria. Between June and October, 2012, the numbers of
      heterotrophic bacteria in rainwater tanks and the values of COD positively
      correlated with the presence of Legionella species. In most of the Legionella
      positive cases, heterotrophic bacterial cell counts were >10(4) CFU/mL. Moreover,
      Legionella species were less frequently detected when the COD value was >5 mg
      KMnO(4)/L. Therefore, at least in Azumino, Japan between June and October 2012,
      both heterotrophic bacterial counts and COD values may be considered index
      parameters for the presence of Legionella cells in rainwater tanks. Much more
      accumulation of such data is needed to verify the accuracy of these findings.

PMID- 24661200
TI  - Activation of Toll-like receptor 9 inhibits lipopolysaccharide-induced receptor
      activator of nuclear factor kappa- B ligand expression in rat B lymphocytes.
AB  - B lymphocytes express multiple TLRs that regulate their cytokine production.We
      investigated the effect of TLR4 and TLR9 activation on receptor activator of NF
      kB ligand (RANKL) expression by rat spleen B cells. Splenocytes or purified
      spleen B cells from Rowett rats were cultured with TLR4 ligand Escherichia coli
      LPS and/or TLR9 ligand CpG-oligodeoxynucleotide (CpG-ODN) for 2 days. RANKL mRNA
      expression and the percentage of RANKL-positive B cells were increased in rat
      splenocytes challenged by E. coli LPS alone. The increases were less pronounced
      when cells were treated with both CpG-ODN and E. coli LPS. Microarray analysis
      showed that expressions of multiple cyclin-dependent kinase (CDK) pathway-related
      genes were up-regulated only in cells treated with both E. coli LPS and CpG-ODN.
      This study suggests that CpG-ODN inhibits LPS-induced RANKL expression in rat B
      cells via regulation of the CDK pathway.

PMID- 24661202
TI  - Global perspectives on poisonous plants: the 9th international symposium on
      poisonous plants.
AB  - The 9th International Symposium on Poisonous Plants (ISOPP9) was held July 15-21,
      2013, at the Inner Mongolia Agricultural University in Hohhot, Inner Mongolia
      Autonomous Region of China. The symposium consisted of three days of oral and
      poster presentations, followed by a tour of the Xilinhot Region of the Mongolian
      Grasslands, encompassing grazing conditions consisting of desert, grassland, and
      steppes. This was the first time that an ISOPP meeting has been held in Asia and
      provided an opportunity for visitors from outside China to become aware of
      livestock poisonings caused by plant species with which they were previously not
      familiar while at the same time demonstrating that many of the problems
      experienced around the world have a common etiology. Presentations focused on
      botany, veterinary science, toxicology, mechanism of action, and chemistry. As is
      appropriate for the Journal of Agricultural and Food Chemistry, this cluster of
      papers consists of selected oral and poster presentations in which the chemistry
      of the toxins played a significant role. The symposium revealed that there is
      considerable scope for isolation, structural elucidation, and analysis of the
      toxins from the numerous poisonous plant species that have been identified in
      China. It became apparent that there are abundant opportunities for chemists both
      within China and abroad to collaborate with Chinese scientists working on
      biological aspects of livestock poisonings. 

PMID- 24661204
TI  - Cytokines and insulin resistance after zoledronic acid-induced acute phase
      response.
AB  - Zoledronic acid is known to induce a transient acute phase response (APR). The
      aim of the study was to investigate whether an APR caused by zoledronic acid
      administration can induce insulin resistance in post-menopausal osteoporotic
      women and the potential involvement of different inflammatory markers, cytokines
      and adipokines to this response. Insulin resistance was calculated by the
      homeostasis model assessment (HOMA-IR). APR symptoms appeared in 30 post
      menopausal osteoporotic women within 24 h and attenuated on day 3 after
      zoledronic acid infusion. Twenty-eight age- and body mass index-matched, patients
      without an APR following zoledronic acid administration, served as a control
      group. In patients with APR, concurrently with a significant increase in serum
      high sensitive C-reactive protein (hsCRP), interleukin-6 (hsIL-6), tumour
      necrosis factor-alpha (hsTNF-alpha) and cortisol levels on days one and two,
      serum insulin was also significantly elevated, resulting in an increased HOMA-IR.
      Leptin and resistin significantly increased on day two in contrast to adiponectin
      which declined, though not statistically significant. The alterations in HOMA-IR
      were mainly associated to the increase of hsCRP and leptin. In conclusion,
      zoledronic acid induces an acute, short term insulin resistance, due to an APR,
      by altering the levels of various adipokines and cytokines.

PMID- 24661205
TI  - Effect of the consonant-vowel structure of written words in Italian.
AB  - Surprisingly little is known about the nature of intermediary sublexical units in
      visual word recognition in Italian, a language with a highly consistent print-to
      sound mapping, which should enhance reliance on grapheme-to-phoneme
      correspondences. In the present study, we examined whether Italian readers are
      sensitive to large orthographic units defined by the consonant-vowel (CV) pattern
      of words and that do not directly map onto linguistic constituents. Participants
      had to judge the number of syllables in written words matched for the number of
      spoken syllables but comprising either one orthographic vowel cluster less than
      the number of syllables (hiatus words, e.g., teatro) or as many vowel clusters as
      syllables (e.g., agosto). Relative to control words, readers were slower and less
      accurate for hiatus words, for which they underestimated the number of syllables.
      This underestimation bias demonstrates that Italian readers are sensitive to
      large orthographic units stemming from a parsing process based on the CV pattern
      that is, the arrangement of consonant and vowel letters. 

PMID- 24661206
TI  - Relationship of epicardial fat thickness with endothelial and cardiac functions
      in children with family history of type 2 diabetes mellitus.
AB  - OBJECTIVE: We hypothesized that many of the pathophysiological mechanisms that
      cause atherosclerotic disease may be present in early childhood in children with
      family history of type 2 diabetes. We aimed to investigate the relation of
      epicardial fat thickness (EFT) with flow-mediated dilatation (FMD) and diastolic
      function in children with family history of type 2 diabetes mellitus. METHODS: We
      measured EFT, FMD, in 209 children (mean age 8.6 + 3.2 years). Children were
      classified into 2 groups: 109 children with a family history of type 2 diabetes
      (group at risk) and 100 healthy children with age and body mass index matched and
      without parental history of diabetes constituted the control group. RESULTS:
      Epicardial fat thickness was significantly increased in group at risk compared
      with control children (P < 0.001), while FMD was significantly lower in group at
      risk versus controls (P < 0.001). EFT was inversely correlated with FMD (r = 
      0.46; P < 0.001), while it was positively correlated with E/E' (r = 0.48; P <
      0.001) and hsCRP (r = 0.39; P < 0.001). Receiver-operating characteristic curve
      analysis revealed a cutoff value of 5 mm for EFT can predict endothelial
      dysfunction in children with family history of DM area under the curve (AUC =
      0.852) with a specificity of 92.2% and a sensitivity of 77.4%. CONCLUSION: Our
      results suggest that children with family history of type 2 diabetes bear
      considerably impaired FMD% and diastolic dysfunction associated with increased
      EFT, that reflecting process that promote the development of cardiovascular
      disease (CVD).

PMID- 24661207
TI  - High throughput screening operations at the University of Kansas.
AB  - The High Throughput Screening Laboratory at University of Kansas plays a critical
      role in advancing academic interest in the identification of chemical probes as
      tools to better understand the biological and biochemical basis of new
      therapeutic targets. The HTS laboratory has an open service policy and
      collaborates with internal and external academia as well as for-profit
      organizations to execute projects requiring HTS-compatible assay development and
      screening of chemical libraries for target validation, probe selection, hit
      identification and lead optimization. 

PMID- 24661203
TI  - Gas what: NO is not the only answer to sexual function.
AB  - The ability to get and keep an erection is important to men for several reasons
      and the inability is known as erectile dysfunction (ED). ED has started to be
      accepted as an early indicator of systemic endothelial dysfunction and
      subsequently of cardiovascular diseases. The role of NO in endothelial relaxation
      and erectile function is well accepted. The discovery of NO as a small signalling
      gasotransmitter led to the investigation of the role of other endogenously
      derived gases, carbon monoxide (CO) and hydrogen sulphide (H2 S) in physiological
      and pathophysiological conditions. The role of NO and CO in sexual function and
      dysfunction has been investigated more extensively and, recently, the involvement
      of H2 S in erectile function has also been confirmed. In this review, we focus on
      the role of these three sister gasotransmitters in the physiology, pharmacology
      and pathophysiology of sexual function in man, specifically erectile function. We
      have also reviewed the role of soluble guanylyl cyclase/cGMP pathway as a common
      target of these gasotransmitters. Several studies have proposed alternative
      therapies targeting different mechanisms in addition to PDE-5 inhibition for ED
      treatment, since some patients do not respond to these drugs. This review
      highlights complementary and possible coordinated roles for these mediators and
      treatments targeting these gasotransmitters in erectile function/ED.

PMID- 24661208
TI  - The high throughput biomedicine unit at the institute for molecular medicine
      Finland: high throughput screening meets precision medicine.
AB  - The High Throughput Biomedicine (HTB) unit at the Institute for Molecular
      Medicine Finland FIMM was established in 2010 to serve as a national and
      international academic screening unit providing access to state of the art
      instrumentation for chemical and RNAi-based high throughput screening. The
      initial focus of the unit was multiwell plate based chemical screening and high
      content microarray-based siRNA screening. However, over the first four years of
      operation, the unit has moved to a more flexible service platform where both
      chemical and siRNA screening is performed at different scales primarily in
      multiwell plate-based assays with a wide range of readout possibilities with a
      focus on ultraminiaturization to allow for affordable screening for the academic
      users. In addition to high throughput screening, the equipment of the unit is
      also used to support miniaturized, multiplexed and high throughput applications
      for other types of research such as genomics, sequencing and biobanking
      operations. Importantly, with the translational research goals at FIMM, an
      increasing part of the operations at the HTB unit is being focused on high
      throughput systems biological platforms for functional profiling of patient cells
      in personalized and precision medicine projects. 

PMID- 24661209
TI  - Developing the Biomolecular Screening Facility at the EPFL into the Chemical
      Biology Screening Platform for Switzerland.
AB  - The Biomolecular Screening Facility (BSF) is a multidisciplinary laboratory
      created in 2006 at the Ecole Polytechnique Federale de Lausanne (EPFL) to perform
      medium and high throughput screening in life sciences-related projects. The BSF
      was conceived and developed to meet the needs of a wide range of researchers,
      without privileging a particular biological discipline or therapeutic area. The
      facility has the necessary infrastructure, multidisciplinary expertise and
      flexibility to perform large screening programs using small interfering RNAs
      (siRNAs) and chemical collections in the areas of chemical biology, systems
      biology and drug discovery. In the framework of the National Centres of
      Competence in Research (NCCR) Chemical Biology, the BSF is hosting 'ACCESS', the
      Academic Chemical Screening Platform of Switzerland that provides the scientific
      community with chemical diversity, screening facilities and know-how in chemical
      genetics. In addition, the BSF started its own applied research axes that are
      driven by innovation in thematic areas related to preclinical drug discovery and
      discovery of bioactive probes. 

PMID- 24661210
TI  - UCLA's Molecular Screening Shared Resource: enhancing small molecule discovery
      with functional genomics and new technology.
AB  - The Molecular Screening Shared Resource (MSSR) offers a comprehensive range of
      leading-edge high throughput screening (HTS) services including drug discovery,
      chemical and functional genomics, and novel methods for nano and environmental
      toxicology. The MSSR is an open access environment with investigators from UCLA
      as well as from the entire globe. Industrial clients are equally welcome as are
      non-profit entities. The MSSR is a fee-for-service entity and does not retain
      intellectual property. In conjunction with the Center for Environmental
      Implications of Nanotechnology, the MSSR is unique in its dedicated and ongoing
      efforts towards high throughput toxicity testing of nanomaterials. In addition,
      the MSSR engages in technology development eliminating bottlenecks from the HTS
      workflow and enabling novel assays and readouts currently not available. 

PMID- 24661211
TI  - Functional genomics down under: RNAi screening in the Victorian Centre for
      Functional Genomics.
AB  - The Victorian Centre for Functional Genomics (VCFG) is an RNAi screening facility
      housed at the Peter MacCallum Cancer Centre in Melbourne, Australia. The Peter
      Mac is Australia's largest dedicated Cancer Research Institute, home to a team of
      over 520 scientists that focus on understanding the genetic risk of cancer, the
      molecular events regulating cancer growth and dissemination and improving
      detection through new diagnostic tools (www.petermac.org). Peter Mac is a well
      recognised technology leader and established the VCFG with a view to enabling
      researchers Australia and New Zealand-wide access to cutting edge functional
      genomics technology, infrastructure and expertise. This review documents the
      technology platforms operated within the VCFG and provides insight into the
      workflows and analysis pipelines currently in operation. 

PMID- 24661212
TI  - UCSF Small Molecule Discovery Center: innovation, collaboration and chemical
      biology in the Bay Area.
AB  - The Small Molecule Discovery Center (SMDC) at the University of California, San
      Francisco, works collaboratively with the scientific community to solve
      challenging problems in chemical biology and drug discovery. The SMDC includes a
      high throughput screening facility, medicinal chemistry, and research labs
      focused on fundamental problems in biochemistry and targeted drug delivery. Here,
      we outline our HTS program and provide examples of chemical tools developed
      through SMDC collaborations. We have an active research program in developing
      quantitative cell-based screens for primary cells and whole organisms; here, we
      describe whole-organism screens to find drugs against parasites that cause
      neglected tropical diseases. We are also very interested in target-based
      approaches for so-called "undruggable", protein classes and fragment-based lead
      discovery. This expertise has led to several pharmaceutical collaborations;
      additionally, the SMDC works with start-up companies to enable their early-stage
      research. The SMDC, located in the biotech-focused Mission Bay neighborhood in
      San Francisco, is a hub for innovative small-molecule discovery research at UCSF.

PMID- 24661213
TI  - Strategic siRNA screening approaches to target cancer at the Cancer Research UK
      Beatson Institute.
AB  - The RNAi Screening Facility at the Cancer Research UK Beatson Institute combines
      siRNA genome-wide screening with drug screening coupled with High Content Imaging
      and fluorescence-based phenotypic assays to target multiple types of cancer.
      Here, we describe the infrastructure of the Facility and the approaches we
      utilise. We also share our experiences in running such a facility and developing
      and executing screening campaigns, with particular regard to high content
      multiparametric analysis, data management and statistical analysis. 

PMID- 24661201
TI  - Chaperoning G protein-coupled receptors: from cell biology to therapeutics.
AB  - G protein-coupled receptors (GPCRs) are membrane proteins that traverse the
      plasma membrane seven times (hence, are also called 7TM receptors). The polytopic
      structure of GPCRs makes the folding of GPCRs difficult and complex. Indeed, many
      wild-type GPCRs are not folded optimally, and defects in folding are the most
      common cause of genetic diseases due to GPCR mutations. Both general and receptor
      specific molecular chaperones aid the folding of GPCRs. Chemical chaperones have
      been shown to be able to correct the misfolding in mutant GPCRs, proving to be
      important tools for studying the structure-function relationship of GPCRs.
      However, their potential therapeutic value is very limited. Pharmacological
      chaperones (pharmacoperones) are potentially important novel therapeutics for
      treating genetic diseases caused by mutations in GPCR genes that resulted in
      misfolded mutant proteins. Pharmacoperones also increase cell surface expression
      of wild-type GPCRs; therefore, they could be used to treat diseases that do not
      harbor mutations in GPCRs. Recent studies have shown that indeed pharmacoperones
      work in both experimental animals and patients. High-throughput assays have been
      developed to identify new pharmacoperones that could be used as therapeutics for
      a number of endocrine and other genetic diseases. 

PMID- 24661214
TI  - The technology development studio of the MPI-CBG: an open access cell-based
      screening facility.
AB  - In the past decade, academic screening centers have been created in many
      universities worldwide. Most of these screening centers are organized as core
      facilities that accept projects from both within their organization and from
      external users in order to maximize staff and instrument usage. The Max Planck
      Institute of Molecular Cell Biology and Genetics in Dresden, Germany, also
      created such a screening facility named the Technology Development Studio (TDS).
      The mission of the facility is to provide cell based screening services focused
      on high resolution confocal imaging. The acquisition of high resolution images
      allows the mathematical description of cells with image analysis to a high degree
      of precision. This precision in turn allows classifying phenotypes accurately and
      compare different cellular treatments to discover underlying mechanisms. 

PMID- 24661215
TI  - Chemical & RNAi screening at MSKCC: a collaborative platform to discover &
      repurpose drugs to fight disease.
AB  - Memorial Sloan Kettering Cancer Center (MSKCC) has implemented the creation of a
      full service state-of-the-art High-throughput Screening Core Facility (HTSCF)
      equipped with modern robotics and custom-built screening data management
      resources to rapidly store and query chemical and RNAi screening data outputs.
      The mission of the facility is to provide oncology clinicians and researchers
      alike with access to cost-effective HTS solutions for both chemical and RNAi
      screening, with an ultimate goal of novel target identification and drug
      discovery. HTSCF was established in 2003 to support the institution's commitment
      to growth in molecular pharmacology and in the realm of therapeutic agents to
      fight chronic diseases such as cancer. This endeavor required broad range of
      expertise in technology development to establish robust and innovative assays,
      large collections of diverse chemical and RNAi duplexes to probe specific
      cellular events, sophisticated compound and data handling capabilities, and a
      profound knowledge in assay development, hit validation, and characterization.
      Our goal has been to strive for constant innovation, and we strongly believe in
      shifting the paradigm from traditional drug discovery towards translational
      research now, making allowance for unmet clinical needs in patients. Our efforts
      towards repurposing FDA-approved drugs fructified when digoxin, identified
      through primary HTS, was administered in the clinic for treatment of stage Vb
      retinoblastoma. In summary, the overall aim of our facility is to identify novel
      chemical probes, to study cellular processes relevant to investigator's research
      interest in chemical biology and functional genomics, and to be instrumental in
      accelerating the process of drug discovery in academia. 

PMID- 24661216
TI  - The parasitic copepod Lernaeocera branchialis negatively affects
      cardiorespiratory function in Gadus morhua.
AB  - The parasitic copepod Lernaeocera branchialis had a negative effect on
      cardiorespiratory function in Atlantic cod Gadus morhua such that it caused
      pronounced cardiac dysfunction with irregular rhythm and reduced stroke amplitude
      compared with uninfected fish. In addition, parasite infection depressed the
      postprandial cardiac output and oxygen consumption. 

PMID- 24661217
TI  - Aspartic protease nepenthesin-1 as a tool for digestion in hydrogen/deuterium
      exchange mass spectrometry.
AB  - Hydrogen/deuterium exchange coupled to mass spectrometry (HXMS) utilizes
      enzymatic digestion of proteins to localize the information about altered
      exchange patterns in protein structure. The ability of the protease to produce
      small peptides and overlapping fragments and provide sufficient coverage of the
      protein sequence is essential for localizing regions of interest. Recently, it
      was shown that there is an interesting group of proteolytic enzymes from
      carnivorous pitcher plants of the genus Nepenthes. In this report, we describe
      successful immobilization and the use of one of these enzymes, nepenthesin-1, in
      HXMS workflow. In contrast to pepsin, it has different cleavage specificities,
      and despite its high inherent susceptibility to reducing and denaturing agents,
      it is very stable upon immobilization and withstands even high concentration of
      guanidine hydrochloride and reducing agents. We show that denaturing agents can
      alter digestion by reducing protease activity and/or substrate solubility, and
      additionally, they influence the trapping of proteolytic peptides onto the
      reversed phase resin. 

PMID- 24661220
TI  - Catalyst-free synthesis of skipped dienes from phosphorus ylides, allylic
      carbonates, and aldehydes via a one-pot SN2' allylation-Wittig strategy.
AB  - A catalyst-free allylic alkylation of stabilized phosphorus ylides with allylic
      carbonates via a regioselective SN2' process is presented. Subsequent one-pot
      Wittig reaction with both aliphatic and aromatic aldehydes as well as ketenes
      provides structurally diverse skipped dienes (1,4-dienes) in generally high
      yields and moderate to excellent stereoselectivity with flexible substituent
      patterns. This one-pot SN2' allylation-Wittig strategy constitutes a convenient
      and efficient synthetic method for highly functionalized skipped dienes from
      readily available starting materials.

PMID- 24661221
TI  - Dose-dependent retinal changes following sodium iodate administration:
      application of spectral-domain optical coherence tomography for monitoring of
      retinal injury and endogenous regeneration.
AB  - BACKGROUND: The purpose of this study was to demonstrate the progression of acute
      retinal injury by correlating histological sections with in vivo spectral-domain
      optical coherence tomography (SD-OCT) images. METHODS: Male C57BL/6 mice were
      treated intravenously with two different sodium iodate (NaIO3) doses (35 mg/kg or
      15 mg/kg). In vivo SD-OCT was performed up to 3 months post-injury. Ex vivo
      retinal histology, TUNEL and IsolectinB4 immunostaining were also conducted.
      Quantitative comparison of histopathological images and SD-OCT images was
      performed. RESULTS: SD-OCT examination revealed that administration of 35 mg/kg
      NaIO3 was associated with progressive and irreversible retinal degeneration. On
      day 3 post-injury, we found numerous apoptotic cells in the outer nuclear layer
      (ONL) that strongly corresponded to hyper-reflective areas in the SD-OCT images.
      At 7 d post-injury, SD-OCT images showed irregular-shaped patterns of hyper
      reflectivity in the retinal pigment epithelium (RPE) that corresponded with the
      accumulation of macrophages phagocytosing melanin granules and cell debris.
      Additionally, we documented hyper-reflective opacities in the vitreous that were
      most numerous at 7 d. At 3 months post-injury, the neurosensory retina was
      significantly thinner, predominantly due to progressive photoreceptor (PR) loss.
      In contrast, administration of 15 mg/kg NaIO3 did not induce hyper-reflectivity
      of ONL in SD-OCT images, which indicates a lack of massive PR cell death. At 3
      months post-injury, SD-OCT images showed the complete restoration of outer retina
      lamination and restoration of hyper-reflective structural bands. Histological
      assessment of retinas acquired after the last SD-OCT imaging session revealed
      complete regeneration of the RPE and considerable improvement of PR architecture.
      CONCLUSIONS: Our findings showed the high level of effectiveness of SD-OCT
      imaging for monitoring dynamic changes in retinal morphology following acute
      retinal injury. Moreover, we demonstrated for the first time that SD-OCT can be
      used to non-invasively detect regeneration in the damaged retina.

PMID- 24661219
TI  - Acetaminophen reactive intermediates target hepatic thioredoxin reductase.
AB  - Acetaminophen (APAP) is metabolized in the liver to N-acetyl-p-benzoquinone imine
      (NAPQI), an electrophilic metabolite known to bind liver proteins resulting in
      hepatotoxicity. Mammalian thioredoxin reductase (TrxR) is a cellular antioxidant
      containing selenocysteine (Sec) in its C-terminal redox center, a highly
      accessible target for electrophilic modification. In the present study, we
      determined if NAPQI targets TrxR. Hepatotoxicity induced by APAP treatment of
      mice (300 mg/kg, i.p.) was associated with a marked inhibition of both cytosolic
      TrxR1 and mitochondrial TrxR2 activity. Maximal inhibition was detected at 1 and
      6 h post-APAP for TrxR1 and TrxR2, respectively. In purified rat liver TrxR1,
      enzyme inactivation was correlated with the metabolic activation of APAP by
      cytochrome P450, indicating that enzyme inhibition was due to APAP-reactive
      metabolites. NAPQI was also found to inhibit TrxR1. NADPH-reduced TrxR1 was
      significantly more sensitive to NAPQI (IC50 = 0.023 MUM) than the oxidized enzyme
      (IC50 = 1.0 MUM) or a human TrxR1 Sec498Cys mutant enzyme (IC50 = 17 MUM),
      indicating that cysteine and selenocysteine residues in the redox motifs of TrxR
      are critical for enzyme inactivation. This is supported by our findings that
      alkylation of reduced TrxR with biotin-conjugated iodoacetamide, which
      selectively reacts with selenol or thiol groups on proteins, was inhibited by
      NAPQI. LC-MS/MS analysis confirmed that NAPQI modified cysteine 59, cysteine 497,
      and selenocysteine 498 residues in the redox centers of TrxR, resulting in enzyme
      inhibition. In addition to disulfide reduction, TrxR is also known to mediate
      chemical redox cycling. We found that menadione redox cycling by TrxR was
      markedly less sensitive to NAPQI than disulfide reduction, suggesting that TrxR
      mediates these reactions via distinct mechanisms. These data demonstrate that
      APAP-reactive metabolites target TrxR, suggesting an additional mechanism by
      which APAP induces oxidative stress and hepatotoxicity. 

PMID- 24661222
TI  - Parallel solution-phase synthesis and general biological activity of a uridine
      antibiotic analog library.
AB  - A small library of ninety four uridine antibiotic analogs was synthesized, under
      the Pilot Scale Library (PSL) Program of the NIH Roadmap initiative, from amine 2
      and carboxylic acids 33 and 77 in solution-phase fashion. Diverse aldehyde,
      sulfonyl chloride, and carboxylic acid reactant sets were condensed to 2, leading
      after acid-mediated hydrolysis, to the targeted compounds 3-32 in good yields and
      high purity. Similarly, treatment of 33 with diverse amines and sulfonamides gave
      34-75. The coupling of the amino terminus of d-phenylalanine methyl ester to the
      free 5'-carboxylic acid moiety of 33 followed by sodium hydroxide treatment led
      to carboxylic acid analog 77. Hydrolysis of this material gave analog 78. The
      intermediate 77 served as the precursor for the preparation of novel dipeptidyl
      uridine analogs 79-99 through peptide coupling reactions to diverse amine
      reactants. None of the described compounds show significant anticancer or
      antimalarial acivity. A number of samples exhibited a variety of promising
      inhibitory, agonist, antagonist, or activator properties with enzymes and
      receptors in primary screens supplied and reported through the NIH MLPCN program.

PMID- 24661223
TI  - Novel effect of the inhibitor of mitochondrial cyclophilin D activation, N-methyl
      4-isoleucine cyclosporin, on renal calcium crystallization.
AB  - OBJECTIVES: To experimentally evaluate the clinical application of N-methyl-4
      isoleucine cyclosporin, a novel selective inhibitor of cyclophilin D activation.
      METHODS: In vitro, cultured renal tubular cells were exposed to calcium oxalate
      monohydrate crystals and treated with N-methyl-4-isoleucine cyclosporin. The
      mitochondrial membrane was stained with tetramethylrhodamine ethyl ester
      perchlorate and observed. In vivo, Sprague-Dawley rats were divided into four
      groups: a control group, an ethylene glycol group (administration of ethylene
      glycol to induce renal calcium crystallization), a N-methyl-4-isoleucine
      cyclosporin group (administration of N-methyl-4-isoleucine cyclosporin) and an
      ethylene glycol + N-methyl-4-isoleucine cyclosporin group (administration of
      ethylene glycol and N-methyl-4-isoleucine cyclosporin). Renal calcium
      crystallization was evaluated using Pizzolato staining. Oxidative stress was
      evaluated using superoxide dismutase and 8-hydroxy-deoxyguanosine. Mitochondria
      within renal tubular cells were observed by transmission electron microscopy.
      Cell apoptosis was evaluated using cleaved caspase-3. RESULTS: In vitro, calcium
      oxalate monohydrate crystals induced depolarization of the mitochondrial membrane
      potential, which was remarkably prevented by N-methyl-4-isoleucine cyclosporin.
      In vivo, ethylene glycol administration induced renal calcium crystallization,
      oxidative stress, mitochondrial collapse and cell apoptosis in rats, which were
      significantly prevented by N-methyl-4-isoleucine cyclosporin. CONCLUSIONS: Herein
      we first report a new treatment agent determining renal calcium crystallization
      through cyclophilin D activation.

PMID- 24661225
TI  - Effects of dutasteride on storage and voiding symptoms in male patients with
      lower urinary tract symptoms as a result of benign prostatic obstruction: the 1
      year outcomes from a prospective urodynamic study.
AB  - OBJECTIVES: To investigate the effects of dutasteride 0.5 mg once daily for 12
      months on lower urinary tract symptoms in treatment-naive patients with benign
      prostatic hyperplasia. METHODS: The present open-label, single-center,
      prospective study recruited 105 outpatients. International Prostate Symptom
      Score, Overactive Bladder Symptom Score, quality of life score testing and Benign
      Prostatic Hyperplasia Impact Index were used for assessing subjective symptoms.
      Urodynamic study including uroflowmetry, cystometry and pressure flow study were
      carried out to evaluate objective symptoms. As parameters of storage function,
      first desire to void, maximum cystometric capacity and occurrence of involuntary
      detrusor contraction were measured, whereas maximum flow rate, detrusor pressure
      at maximum flow rate, post-void residual urine and bladder outlet obstruction
      index were assessed as parameters of voiding function. Wilcoxon's rank-sum test,
      Student's t-test and the chi(2)-test were carried out to evaluate changes in
      subjective and objective symptoms. RESULTS: A total of 97 patients with a mean
      age of 68.8 years and mean prostate volume of 57.6 mL were included in the
      analysis. Subjective symptom parameters improved significantly after 2 months,
      and progressively improved until after 12 months. Significant improvements in
      storage function objective parameters and voiding function objective parameters
      were observed after 6 months, and further improvements were obtained after 12
      months. CONCLUSIONS: Dutasteride is effective in relieving lower urinary tract
      symptoms by improving storage and voiding function, as well as subjective
      symptoms in patients with benign prostatic hyperplasia.

PMID- 24661224
TI  - Congestive heart failure risk in cancer patients treated with vascular
      endothelial growth factor tyrosine kinase inhibitors: a systematic review and
      meta-analysis of 36 clinical trials.
AB  - AIMS: Congestive heart failure (CHF) associated with vascular endothelial growth
      factor tyrosine-kinase inhibitors (VEGFR-TKIs) has emerged as a relevant problem
      in clinical and scientific communities. We performed an up-to-date, comprehensive
      meta-analysis to determine the overall incidence and risk of CHF in cancer
      patients receiving VEGFR-TKIs. METHODS: The databases of PubMed, Web of Science
      and abstracts presented at the American Society of Clinical Oncology up to August
      31 2013 were searched for relevant articles. Statistical analyses were conducted
      to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals
      (CIs) by using either random effects or fixed effect models according to the
      heterogeneity of included studies. RESULTS: A total of 10 553 patients from 36
      clinical trials were included. The overall incidence of all grade and high grade
      CHF associated with VEGFR-TKIs was 3.2% (95% CI 1.8%, 5.8%) and 1.4% (95% CI
      0.9%, 2.3%), respectively. The use of VEGFR-TKIs significantly increased the risk
      of developing all grade (OR 2.37, 95% CI 1.76, 3.20, P < 0.001) and high grade
      (OR 3.51, 95% CI 1.74, 7.05, P < 0.001) CHF. In subgroup analyses, the risk of
      CHF did not significantly vary with tumour types (P = 0.071 for all grade; P =
      0.72 for high grade) and VEGFR-TKIs (P = 0.55 for all grade; P = 0.99 for high
      grade). Meta-regression indicated that CHF might possibly occur early in the
      treatment of VEGFR-TKIs. No evidence of publication bias was observed.
      CONCLUSION: The use of VEGFR-TKIs is associated with a significantly increased
      risk of developing congestive heart failure in cancer patients. Clinicians should
      be aware of this risk and provide close monitoring in patients receiving these
      therapies.

PMID- 24661227
TI  - Mass spectrometry-based plasma proteomics: state of the art and future outlook.
AB  - Mass spectrometry-based plasma proteomics is a field where intense research has
      been performed during the last decade. Being closely linked to biomarker
      discovery, the field has received a fair amount of criticism, mostly due to the
      low number of novel biomarkers reaching the clinic. However, plasma proteomics is
      under gradual development with improvements on fractionation methods, mass
      spectrometry instrumentation and analytical approaches. These recent developments
      have contributed to the revival of plasma proteomics. The goal of this review is
      to summarize these advances, focusing in particular on fractionation methods,
      both for targeted and global mass spectrometry-based plasma analysis. 

PMID- 24661226
TI  - Dose effect of thiazolidinedione on cancer risk in type 2 diabetes mellitus
      patients: a six-year population-based cohort study.
AB  - WHAT IS KNOWN AND OBJECTIVE: Prior studies found that thiazolidinediones (TZDs)
      might have tumour-suppressor activity mediated through cell-cycle arrest,
      induction of apoptosis and inhibition of cell invasion. The main objective of
      this study was to investigate the effects of TZDs on the risk of cancer among
      patients with type 2 diabetes mellitus (DM). METHODS: Patients diagnosed with DM
      between 1 January 1998 and 31 December 2002 were identified from the Longitudinal
      Health Insurance Database (LHID) within the Taiwan National Health Insurance
      (NHI) programme. Using Cox regression models, we assessed the association between
      prescribed TZDs and cancer risk, TZDs' dose effect and the association between
      TZDs and specific cancer types. Hazard ratios (HR) were adjusted for potential
      confounders (age, gender, income, Charlson score index, metformin and insulin
      use). RESULTS AND DISCUSSION: The adjusted HRs for those prescribed TZD were 0.74
      (95% CI 0.43-1.26, P = 0.27), 0.39 (95% CI 0.33-0.45, P < 0.001) and 0.49 (95% CI
      0.27-0.89, P = 0.02), respectively, relative to non-DM patients, DM patients
      prescribed other anti-DM drugs besides TZDs and DM patients not prescribed any
      anti-DM drugs. In addition, the effects of TZDs were shown to be significantly
      dose dependent (P for trend < 0.001). The risk of breast, brain, colorectal, ear
      nose-throat, kidney, liver, lung, lymphatic, prostate, stomach, and uterus cancer
      was significantly lower in those prescribed TZDs. WHAT IS NEW AND CONCLUSIONS:
      The results showed a decrease in cancer risk in diabetic patients using TZD, and
      the association was dose dependent.

PMID- 24661229
TI  - Recent advances in tree hydraulics highlight the ecological significance of the
      hydraulic safety margin.

PMID- 24661228
TI  - The potential of pralatrexate as a treatment of peripheral T-cell lymphoma.
AB  - INTRODUCTION: Peripheral T-cell lymphomas (PTCLs) are a group of rare
      malignancies originating from clonal proliferation of mature, post-thymic T cells
      that represent 10 - 15% of all non-Hodgkin's lymphomas with poor prognosis and
      median survival of 1 - 3 years. The standard treatment for PTCL has not yet been
      identified. Many patients with PTCL are refractory to first-line therapy. The
      complete response rate ranges from 36 to 66% according to different PTCL
      subtypes. Furthermore, those who reached a complete or partial response often
      have a shorter progression-free survival. AREAS COVERED: This paper discusses the
      potential of pralatrexate , a methotrexate analogue, as a treatment of PTCL. The
      authors report on the efficacy and safety data of controlled studies and describe
      the end points of ongoing trials. Pralatrexate was the first drug to obtain FDA
      approval for the treatment of patients with relapsed or refractory PTCL. However,
      the European Medicines Agency has refused marketing authorization. EXPERT
      OPINION: None of the treatments commonly used today have given satisfactory
      results. Pralatrexate seems to be one of the most promising agents in the
      treatment of patients with PTCL. Future efforts should be focused on better
      understanding the molecular pathogenesis of PTCL and on specific trials for
      different PTCL subtypes using rational drug combinations that include
      pralatrexate.

PMID- 24661230
TI  - CD4(+)CD25(high) FOXP3(+) regulatory T cells correlate with FEV1 in North Indian
      children with cystic fibrosis.
AB  - Cystic fibrosis (CF) lung disease is characterized by dysregulated inflammatory
      response in the airways. CD4(+)CD25(+) regulatory T cells play a crucial role in
      maintaining the immune homeostasis. However their role in the disease
      pathogenesis of CF remains unexplored. AIM: To determine the percentage of
      circulating CD4(+)CD25(high), FoxP3(+) T cell expression in children with CF and
      controls. Furthermore to evaluate the relationship between CD4(+)CD25(high),
      FOXP3 T cell % and the clinical status of the disease (lung function). METHODS:
      CD4(+)CD25(+), intracellular FoxP3 expression in peripheral blood were estimated
      using flowcytometry in 20 children with CF and 10 healthy controls. Spirometry
      was carried out according to the standard guidelines. RESULTS: We observed a
      significant difference in CD4(+)CD25(+)T cell% in children with CF (5.2 +/- 1.2)
      versus controls (6.8 +/- 1.4, p < 0.05), CD4(+)CD25(high)T cell% in CF (1.72 +/-
      0.36) versus controls (2.59 + 0.42, p < 0.003). Similarly a significant
      difference was observed in FoxP3 T cell% CF: (60.7 +/- 6.19) versus controls
      (76.8 +/- 5.16), p < 0.001. A significant positive correlation between FoxP3 T
      cell% and FEV1 in children with CF(r = 0.822, p < 0.01) was
      observed.CD4(+)CD25(high) T cell% correlated positively with FEV1 (r = 0.742, p <
      0.01). CONCLUSION: Our findings report the first evidence of a decreased
      expression of circulating CD4(+)CD25(high) FoxP3(+) T cells in children with CF.
      Furthermore circulating CD4+ CD25(high), FOXP3(+) T cell percentage correlated
      with FEV1.

PMID- 24661231
TI  - Dynamic characteristics of the novel strobilurin fungicide SYP-3343 in aerobic
      soils.
AB  - SYP-3343, (E)-2-(2-((3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5
      yloxy)methyl)phenyl)-3-methoxyacrylate, is a newly developed strobilurin
      fungicide. However, the environmental behavior and fate of SYP-3343 in soil have
      not been well-documented. In this study, 14C-labeled SYP-3343 was employed to
      investigate the dynamic characteristics in three typical soils under aerobic
      conditions. Radioactivity analysis after high-performance liquid chromatography
      (HPLC) showed that SYP-3343 degraded rapidly in the coastal soil with a half-life
      of 43.8 days. After incubation of 100 days, its extractable residues were greater
      than 76.0% and bound residues were less than 12.4%, indicating that SYP-3343 was
      not easy to accumulate in soils. The mineralization to 14CO2 reached 5.4% for
      acidic soil, 2.8% for neutral soil, and 1.7% for alkaline soil, suggesting that
      it was difficult to cleave the pyrazole ring completely. In addition, dynamic
      characteristics of SYP-3343 in sterile and non-sterile loamy soil showed that
      soil microbes affected SYP-3343 residue in soil and could accelerate the process
      of degradation and mineralization.

PMID- 24661232
TI  - Pennies from heaven? Conceptions and earmarking of lottery prize money.
AB  - The source of money has been shown to be important for how money is spent. In
      addition, sudden wealth is often associated with social and psychological risks.
      This article investigates if conceptions of lottery prize money--as a special
      kind of money--imply restrictions on how it can be spent. Analysis of interviews
      with lottery winners shows that interviewees use earmarking of the prize money as
      a strategy for avoiding the pitfalls associated with a lottery win. Conceptions
      of lottery prize money as 'a lot' or as 'a little', as shared or personal, and as
      an opportunity or a risk, influences the ends for which it is earmarked: for self
      serving spending, a 'normal' living standard, paying off loans, saving for
      designated purposes, or for economic security and independence. Clearly defining
      and earmarking lottery prize money thus helps lottery winners construe their
      sudden wealth, not as a risk, but as 'pennies from heaven.'

PMID- 24661233
TI  - Effect of photodynamic therapy with hypocrellin B on apoptosis, adhesion, and
      migration of cancer cells.
AB  - PURPOSE: In the present study, we investigated effects of photodynamic therapy
      with hypocrellin B on apoptosis, adhesion, and migration of cancer cells in
      vitro. MATERIALS AND METHODS: Human ovarian cancer HO-8910 cell as a cancer model
      cell was incubated with hypocrellin B at a concentration of 2.5 MUM for 5 h and
      irradiated by light from a light-emitting diodes (LED) source. Cell apoptosis was
      analyzed by flow cytometry with annexin V/propidium iodide (PI) staining and
      nuclear staining 6 h after hypocrellin B photoirradiation. Cell adhesion was
      assessed using the 3-(4, 5-dimthylthiazol-2-yl)-2, 5 diphenyl-tetrazolium bromide
      (MTT) assay 4 h after photodynamic treatment. Cell migration was measured 48 h
      after photodynamic treatment. RESULTS: Flow cytometry with annexin V/PI staining
      showed that early apoptotic and late apoptotic (necrotic) rates following
      photodynamic therapy with hypocrellin B markedly increased to 16.40% and 24.67%,
      respectively. Nuclear staining found nuclear condensation and typical apoptotic
      body in the treated cells. The number of cell migration was significantly
      decreased to 183 +/- 28 after photodynamic therapy with hypocrellin B (p < 0.01).
      Light irradiation alone and hypocrellin B alone had no significant effect on cell
      migration. The cell adhesion inhibitory rate due to photodynamic action of
      hypocrellin B was 53.2 +/- 1.8%, significantly higher than 2.7 +/- 2.1% of light
      treatment alone and 1.0 +/- 0.4% of hypocrellin B treatment alone (p < 0.01).
      CONCLUSION: The findings demonstrated that photodynamic therapy with hypocrellin
      B remarkably induced apoptosis and inhibited adhesion and migration of cancer
      cells in vitro.

PMID- 24661234
TI  - The Swedish implementation of multisystemic therapy for adolescents: does
      treatment experience predict treatment adherence?
AB  - Treatment effects may not be observed if an empirically supported intervention is
      not administered with treatment adherence. This retrospective study investigated
      how therapists' adherence to Multisystemic therapy (MST) varied during a 6-year
      period in Sweden. Adherence was measured using the Therapist Adherence Measure,
      which was provided by caregivers. The associations between treatment adherence
      and therapist-reported posttreatment youth outcomes were also assessed.
      Retrospective adherence data were obtained for 973 families with youths between
      12 and 17 years old who received MST from 68 therapists divided into 10 teams.
      Implementation of MST occurred in 2 waves between March 2003 and August 2009.
      Multilevel structural equation modelling was used to evaluate family- and cohort
      level predictors and outcomes of treatment adherence. The results confirm
      previous research: Treatment adherence predicts MST treatment outcomes. With
      respect to the relationship between MST treatment experience and MST treatment
      adherence, the analysis showed mixed results. An increase in years that a team
      had been active predicted an increase in therapist adherence to MST. Therapists
      from the 2nd implementation wave had higher therapist adherence rates than
      therapists from the 1st implementation wave. Nevertheless, a therapists'
      experience with MST did not predict MST treatment adherence. The results suggest
      that the found links among treatment experience, treatment adherence, and
      treatment outcomes provide support for the hypothesis that the collective
      experience of the team members promotes treatment adherence. However, results are
      mixed and further research is needed. 

PMID- 24661235
TI  - Comparison of the anaesthetic efficacy of different volumes of 4% articaine (1.8
      and 3.6 mL) as supplemental buccal infiltration after failed inferior alveolar
      nerve block.
AB  - AIM: To compare the anaesthetic efficacy of different volumes (1.8 mL vs. 3.6 mL)
      of 4% articaine with 1 : 100 000 epinephrine injected as buccal infiltrations
      after a failed inferior alveolar nerve block (IANB) in patients with symptomatic
      irreversible pulpitis. METHODOLOGY: Two hundred and thirty-four adult patients,
      diagnosed with irreversible pulpitis in a mandibular tooth, participated in this
      multicentre, randomized double-blinded trial. Patients received IANB with 1.8 mL
      of 4% articaine with 1 : 100 000 epinephrine. Pain during treatment was recorded
      using the Heft-Parker visual analogue scale (HP VAS). The primary outcome
      measure, and the definition of 'success', was the ability to undertake pulp
      chamber access and canal instrumentation with no or mild pain (HP VAS score <55
      mm). Patients who experienced 'moderate-to-severe' pain (HP VAS score >= 55 mm)
      were randomly allocated into two groups and received buccal infiltrations with
      either 1.8 mL or 3.6 mL of 4% articaine with 1 : 100 000 epinephrine. Root canal
      treatment was re-initiated after 10 min. Success was again defined as no pain or
      weak/mild pain during endodontic access preparation and instrumentation.
      Statistical analysis was performed using Mann-Whitney U and chi-square tests.
      RESULTS: The initial IANB of 4% articaine gave an overall success rate of 37%.
      The success rate of supplementary buccal infiltration with 1.8 and 3.6 mL volumes
      was 62% and 64%, respectively. The difference between the success rates of the
      two volumes was not statistically significant. CONCLUSIONS: Increasing the volume
      of 4% articaine with 1 : 100 000 epinephrine from 1.8 to 3.6 mL, given as
      supplementary buccal infiltrations after a failed primary IANB with 1.8 mL of 4%
      articaine with 1 : 100 000, did not improve the anaesthetic success rates in
      patients with symptomatic irreversible pulpitis.

PMID- 24661236
TI  - Application of micro-attenuated total reflectance Fourier transform infrared
      spectroscopy to ink examination in signatures written with ballpoint pen on
      questioned documents.
AB  - Questioned documents examined in a forensic laboratory sometimes contain
      signatures written with ballpoint pen inks; these signatures were examined to
      assess the feasibility of micro-attenuated total reflectance (ATR) Fourier
      transform infrared (FTIR) spectroscopy as a forensic tool. Micro-ATR FTIR spectra
      for signatures written with 63 ballpoint pens available commercially in Korea
      were obtained and used to construct an FTIR spectral database. A library
      searching program was utilized to identify the manufacturer, blend, and model of
      each black ballpoint pen ink based upon their FTIR peak intensities, positions,
      and patterns in the spectral database. This FTIR technique was also successfully
      used in determining the sequence of homogeneous line intersections from the
      crossing lines of two ballpoint pen signatures. We have demonstrated with a set
      of sample documents that micro-ATR FTIR is a viable nondestructive analytical
      method that can be used to identify the origin of the ballpoint pen ink used to
      mark signatures. 

PMID- 24661237
TI  - Biopsy-proven spontaneous regression of a rhabdomyomatous mesenchymal hamartoma.
AB  - Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare, benign, congenital tumor
      of the dermis and subcutaneous tissue comprised of skeletal muscle and adipose
      and adnexal elements. Although the majority of cases are an incidental finding in
      otherwise healthy patients, some have been reported in association with other
      anomalies. We present a full-term boy evaluated on day 2 of life for two lesions
      located on the midline of the lower back and right buttock that each appeared
      clinically as an atrophic, pink plaque. Ultrasound of the midline lesion revealed
      an underlying lipomyelomeningocele with a tethered cord in the spinal canal.
      Histopathology of the right buttock cutaneous lesion was consistent with a
      diagnosis of RMH. Surgical excision was performed on the midline intradural
      lipoma and the lesion on the buttock was monitored clinically. Repeat biopsy of
      this site at 1 year of age revealed complete spontaneous regression. This case
      highlights three interesting features: the association with an occult spinal
      dysraphism lipomyelomeningocele and tethered cord, the clinical presentation of
      an atrophic plaque as opposed to the more commonly reported raised lesions, and
      the phenomenon of spontaneous regression of the lesion. Most importantly, this
      final feature of regression in our patient suggests that, in the absence of
      symptoms, clinical observation of RMH lesions is warranted for spontaneous
      regression for 1 to 2 years provided that no functional deficit is noted and that
      the cutaneous or deeper lesions are not causing a medical problem.

PMID- 24661238
TI  - New reactions of terminal hydrides on a diiron dithiolate.
AB  - Mechanisms for biological and bioinspired dihydrogen activation and production
      often invoke the intermediacy of diiron dithiolato dihydrides. The first example
      of such a Fe2(SR)2H2 species is provided by the complex [(term-H)(MU
      H)Fe2(pdt)(CO)(dppv)2] ([H1H](0)). Spectroscopic and computational studies
      indicate that [H1H](0) contains both a bridging hydride and a terminal hydride,
      which, notably, occupies a basal site. The synthesis begins with [(MU
      H)Fe2(pdt)(CO)2(dppv)2](+) ([H1(CO)](+)), which undergoes substitution to afford
      [(MU-H)Fe2(pdt)(CO)(NCMe)(dppv)2](+) ([H1(NCMe)](+)). Upon treatment of
      [H1(NCMe)](+) with borohydride salts, the MeCN ligand is displaced to afford
      [H1H](0). DNMR (EXSY, SST) experiments on this complex show that the terminal and
      bridging hydride ligands interchange intramolecularly at a rate of 1 s(-1) at -40
      degrees C. The compound reacts with D2 to afford [D1D](0), but not mixed
      isotopomers such as [H1D](0). The dihydride undergoes oxidation with Fc(+) under
      CO to give [1(CO)](+) and H2. Protonation in MeCN solution gives [H1(NCMe)](+)
      and H2. Carbonylation converts [H1H](0) into [1(CO)](0). 

PMID- 24661240
TI  - GnRH-Gemcitabine conjugates for the treatment of androgen-independent prostate
      cancer: pharmacokinetic enhancements combined with targeted drug delivery.
AB  - Gemcitabine, a drug with established efficacy against a number of solid tumors,
      has therapeutic limitations due to its rapid metabolic inactivation. The aim of
      this study was the development of an innovative strategy to produce a
      metabolically stable analogue of gemcitabine that could also be selectively
      delivered to prostate cancer (CaP) cells based on cell surface expression of the
      Gonadotropin Releasing Hormone-Receptor (GnRH-R). The synthesis and evaluation of
      conjugated molecules, consisting of gemcitabine linked to a GnRH agonist, is
      presented along with results in androgen-independent prostate cancer models. NMR
      and ligand binding assays were employed to verify conservation of
      microenvironments responsible for binding of novel GnRH-gemcitabine conjugates to
      the GnRH-R. In vitro cytotoxicity, cellular uptake, and metabolite formation of
      the conjugates were examined in CaP cell lines. Selected conjugates were
      efficacious in the in vitro assays with one of them, namely, GSG, displaying high
      antiproliferative activity in CaP cell lines along with significant metabolic and
      pharmacokinetic advantages in comparison to gemcitabine. Finally, treatment of
      GnRH-R positive xenografted mice with GSG showed a significant advantage in tumor
      growth inhibition when compared to gemcitabine. 

PMID- 24661241
TI  - Robot-assisted radical prostatectomy in the Korean population: a 5-year
      propensity-score matched comparative analysis versus open radical prostatectomy.
AB  - OBJECTIVES: To compare the oncological outcomes of robot-assisted laparoscopic
      radical prostatectomy with those of open radical prostatectomy in contemporary
      Korean prostate cancer patients. METHODS: From a group of 1172 patients
      consisting of 592 (50.5%) robot-assisted laparoscopic radical prostatectomy and
      580 (49.5%) open radical prostatectomy cases carried out between 1992 and 2008,
      175 robot-assisted laparoscopic radical prostatectomy cases were matched with an
      equal number of open radical prostatectomy cases by propensity scoring based on
      patient age, preoperative prostate-specific antigen, biopsy Gleason score and
      clinical tumor stage. Competing-risks survival analyses were used to evaluate
      oncological outcomes, including rates of positive surgical margin, biochemical
      recurrence, adjuvant therapy, cancer-specific survival, overall survival and
      metastasis-free survival during the mean follow up of 58.4 months. RESULTS:
      Positive surgical margin rates were comparable between robot-assisted
      laparoscopic radical prostatectomy and open radical prostatectomy cohorts (19.4%
      vs 21.8%), with comparable rates for all pathological stages and risk subgroups.
      Positive surgical margin rates according to location were comparable, with the
      apical margin being the most common location. Robot-assisted laparoscopic radical
      prostatectomy recovered higher lymph node yields compared with open radical
      prostatectomy (12.5 vs 3.8; P < 0.001). The robot-assisted laparoscopic radical
      prostatectomy and the open radical prostatectomy groups showed equal oncological
      outcomes regarding 5-year biochemical recurrence-free survival (log-rank P =
      0.651), metastasis-free survival (log-rank P = 0.876), cancer-specific survival
      (log-rank P = 0.076) and overall survival (log-rank P = 0.648), respectively.
      Between groups, there was no difference in the rate of adjuvant therapy, time to
      first adjuvant therapy failure or in the rate of subsequent secondary treatment.
      CONCLUSIONS: Robot-assisted laparoscopic radical prostatectomy represents an
      effective surgical approach for the treatment of prostate cancer in the Korean
      population, as it provides equivalent oncological outcomes to open radical
      prostatectomy.

PMID- 24661242
TI  - Knitted fabrics made from highly conductive stretchable fibers.
AB  - We report knitted fabrics made from highly conductive stretchable fibers. The
      maximum initial conductivity of fibers synthesized by wet spinning was 17460 S
      cm(-1) with a rupture tensile strain of 50%. The maximum strain could be
      increased to 490% by decreasing the conductivity to 236 S cm(-1). The knitted
      fabric was mechanically and electrically reversible up to 100% tensile strain
      when coated by poly(dimethylsiloxane). The normalized resistance of the
      poly(dimethylsiloxane)-coated fabric decreased to 0.65 at 100% strain. 

PMID- 24661243
TI  - An integrated perspective and functional impact of the mitochondrial acetylome.
AB  - Growing evidence suggests that a range of reversible protein post-translational
      modifications such as acetylation regulates mitochondria signalling, impacting
      cellular homeostasis. However, the extent of this type of regulation in the
      control of mitochondria functionality is just beginning to be discovered, aided
      by the availability of high-resolution mass spectrometers and bioinformatic
      tools. Data mining from literature on protein acetylation profiling focused on
      mitochondria isolated from tissues retrieved more than 1395 distinct proteins,
      corresponding to more than 4858 acetylation sites. ClueGo analysis of identified
      proteins highlighted oxidative phosphorylation, tricarboxylic acid cycle, fatty
      acid oxidation and amino acid metabolism as the biological processes more prone
      to regulation through acetylation. This review also examines the physiological
      relevance of protein acetylation on the molecular pathways harbored in
      mitochondria under distinct pathophysiological conditions as caloric restriction
      and alcohol-induced liver damage. This integrative perspective will certainly
      help to envisage future studies targeting the regulation of mitochondrial
      functionality.

PMID- 24661244
TI  - With malice toward none and charity for some: ingroup favoritism enables
      discrimination.
AB  - Dramatic forms of discrimination, such as lynching, property destruction, and
      hate crimes, are widely understood to be consequences of prejudicial hostility.
      This article focuses on what has heretofore been only an infrequent countertheme
      in scientific work on discrimination-that favoritism toward ingroups can be
      responsible for much discrimination. We extend this counterthesis to the strong
      conclusion that ingroup favoritism is plausibly more significant as a basis for
      discrimination in contemporary American society than is outgroup-directed
      hostility. This conclusion has implications for theory, research methods, and
      practical remedies.

PMID- 24661245
TI  - Breast lesions: evaluation with shear wave elastography, with special emphasis on
      the "stiff rim" sign.
AB  - PURPOSE: To analyze the diagnostic performance of shear wave elastography (SWE)
      in differentiating between benign and malignant breast lesions, with special
      emphasis on the value of the "stiff rim" sign, as compared with conventional
      ultrasonography (US). MATERIALS AND METHODS: For this ethics committee-approved
      retrospective study, all patients provided verbal informed consent for the
      analysis of their imaging data. A total of 193 consecutive women (age range, 18
      82 years; mean age, 46 years) with 193 breast lesions (56 malignant, 137 benign)
      were included. The stiff rim sign, a qualitative SWE feature, was evaluated at
      the display setting of less than 180 kPa and at 180 kPa. The quantitative SWE
      features were assessed. Sensitivity, specificity, the area under the receiver
      operating characteristic curve (Az), and positive and negative likelihood ratios
      were calculated for conventional US features, for SWE features, and for combined
      conventional US and SWE features. RESULTS: Among all qualitative and quantitative
      SWE features, the stiff rim sign at the display setting (<180 kPa) showed the
      highest Az (0.918; 95% confidence interval [CI]: 0.870, 0.953), which was
      comparable to that for conventional US (0.891; 95% CI: 0.838, 0.931) (P = .40).
      The combination of the stiff rim sign at less than 180 kPa and conventional US
      features, with a positive likelihood ratio of 12.23 (95% CI: 11.5, 13.0) and a
      negative likelihood ratio of 0.02 (95% CI: 0.003, 0.1), yielded the highest Az
      (0.982; 95% CI: 0.951, 0.995)-higher than those for conventional US only and for
      any single SWE feature alone (P < .001 for all)-and yielded higher sensitivity
      (98.2% [55 of 56]; 95% CI: 90.4%, 100.0%) and similar specificity (92.0% [126 of
      137]; 95% CI: 86.1%, 95.9%) compared with conventional US (P < .001 and P = .58,
      respectively). With use of this combination, the rate of recommendation of benign
      lesions for interventional procedures would decrease from 56.9% (78 of 137) (on
      the basis of conventional US features) to 15.3% (21 of 137), and 100.0% (56 of
      56) (95% CI: 93.6%, 100.0%) malignant lesions would be correctly selected for
      biopsy. CONCLUSION: Adding SWE features, especially the stiff rim sign at the
      display setting (<180 kPa), to conventional US has the potential to improve the
      differentiation of breast lesions.

PMID- 24661246
TI  - Pathologically proved nonspecific interstitial pneumonia: CT pattern analysis as
      compared with usual interstitial pneumonia CT pattern.
AB  - PURPOSE: To assess the variability of computed tomography (CT) patterns in
      patients with pathologic nonspecific interstitial pneumonia (NSIP) and to
      evaluate correlation of CT patterns with new idiopathic pulmonary fibrosis (IPF)
      classification guidelines, including pathologic diagnosis and predicted
      mortality. MATERIALS AND METHODS: The ethical review boards of the five
      institutions that contributed cases waived the need for informed consent for
      retrospective review of patient records and images. The study included 114
      patients with (a) a pathologic diagnosis of idiopathic NSIP (n = 39) or (b) a
      pathologic diagnosis of usual interstitial pneumonia (UIP) and a clinical
      diagnosis of IPF (n = 75). Two groups of independent observers evaluated the
      extent and distribution of various CT findings and identified the following five
      patterns: UIP, possible UIP, indeterminate (either UIP or NSIP), NSIP, and
      suggestive of an alternative diagnosis. CT findings were compared with pathologic
      diagnoses and outcome from clinical findings by using the log-rank test and
      Kaplan-Meier curves. RESULTS: Radiologists classified 17 cases as UIP, 24 as
      possible UIP, 13 as indeterminate (either UIP or NSIP), and 56 as NSIP. In 35 of
      39 patients with pathologic NSIP, a diagnosis of NSIP was made with CT. On the
      basis of CT interpretations, the mean overall survival time of patients with UIP,
      possible UIP, indeterminate findings, or NSIP was 33.5, 73.0, 101.0, and 140.2
      months, respectively. Outcome of patients with a CT diagnosis of UIP was
      significantly worse than that of patients with a pattern of possible UIP,
      indeterminate findings, or NSIP (log-rank test: P = .013, P = .018, and P < .001,
      respectively). CONCLUSION: CT pattern in patients with pathologic NSIP is more
      uniform than that in patients with pathologic UIP, and CT NSIP pattern is
      associated with better patient outcome than is CT UIP pattern.

PMID- 24661247
TI  - Data-driven grading of brain gliomas: a multiparametric MR imaging study.
AB  - PURPOSE: To grade brain gliomas by using a data-driven analysis of
      multiparametric magnetic resonance (MR) imaging, taking into account the
      heterogeneity of the lesions at MR imaging, and to compare these results with the
      most widespread current radiologic reporting methods. MATERIALS AND METHODS: One
      hundred eighteen patients with histologically confirmed brain gliomas were
      evaluated retrospectively. Conventional and advanced MR sequences (perfusion
      weighted imaging, MR spectroscopy, and diffusion-tensor imaging) were performed.
      Three evaluations were conducted: semiquantitative (based on conventional and
      advanced sequences with reported cutoffs), qualitative (exclusively based on
      conventional MR imaging), and quantitative. For quantitative analysis, four
      volumes of interest were placed: regions with contrast material enhancement,
      regions with highest and lowest signal intensity on T2-weighted images, and
      regions of most restricted diffusivity. Statistical analysis included t test,
      receiver operating characteristic (ROC) analysis, discriminant function analysis
      (DFA), leave-one-out cross-validation, and Kendall coefficient of concordance.
      RESULTS: Significant differences were noted in age, relative cerebral blood
      volume (rCBV) in contrast-enhanced regions (cutoff > 2.59; sensitivity, 80%;
      specificity, 91%; area under the ROC curve [AUC] = 0.937; P = .0001), areas of
      lowest signal intensity on T2-weighted images (>2.45, 57%, 97%, 0.852, and P =
      .0001, respectively), restricted diffusivity regions (>2.61, 54%, 97%, 0.808, and
      P = .0001, respectively), and choline/creatine ratio in regions with the lowest
      signal intensity on T2-weighted images (>2.07, 49%, 88%, 0.685, and P = .0007,
      respectively). DFA that included age; rCBV in contrast-enhanced regions, areas of
      lowest signal intensity on T2-weighted images, and areas of restricted
      diffusivity; and choline/creatine ratio in areas with lowest signal intensity on
      T2-weighted images was used to classify 95% of patients correctly. Quantitative
      analysis showed a higher concordance with histologic findings than qualitative
      and semiquantitative methods (P < .0001). CONCLUSION: A quantitative
      multiparametric MR imaging evaluation that incorporated heterogeneity at MR
      imaging significantly improved discrimination between low- and high-grade brain
      gliomas with a very high AUC (ie, 0.95), thus reducing the risk of inappropriate
      or delayed surgery, respectively.

PMID- 24661249
TI  - Slow and fast singlet energy transfers in BODIPY-gallium(III)corrole dyads linked
      by flexible chains.
AB  - Red (no styryl), green (monostyryl), and blue (distyryl) BODIPY-gallium(III)
      (BODIPY = boron-dipyrromethene) corrole dyads have been prepared in high yields
      using click chemistry, and their photophysical properties are reported. An
      original and efficient control of the direction of the singlet energy transfers
      is reported, going either from BODIPY to the gallium-corrole units or from
      gallium-corroles to BODIPY, depending upon the nature of the substitution on
      BODIPY. In one case (green), both directions are possible. The mechanism for the
      energy transfers is interpreted by means of through-space Forster resonance
      energy transfer (FRET). 

PMID- 24661248
TI  - MR arthrography: impact of steroids, local anesthetics, and iodinated contrast
      material on gadolinium signal intensity in phantoms at 1.5 and 3.0 T.
AB  - PURPOSE: To determine if gadolinium signal intensity at direct magnetic resonance
      (MR) arthrography is affected by the addition of steroids, anesthetics, or
      iodinated contrast material. MATERIALS AND METHODS: This study did not require
      approval by the institutional review board because no patients or patient data
      were involved. An in vitro study was performed to evaluate various concentrations
      of three gadolinium contrast agents (gadopentetate dimeglumine, gadobenate
      dimeglumine, and gadofosveset trisodium) diluted in either saline or iodinated
      contrast material (50% and full-strength iohexol 300). Three steroids
      (betamethasone, triamcinolone, and methylprednisolone) and three local
      anesthetics (lidocaine, ropivacaine, and bupivacaine) were added to solutions in
      clinical doses. T1-weighted fat-suppressed MR imaging sequences were performed in
      phantoms at 1.5 and 3.0 T. Signal intensities were measured. All experiments were
      repeated in full for a total of three replications each. The data were analyzed
      by using two-way factorial analysis of variance. RESULTS: Dilution of gadolinium
      into iohexol reduced the signal intensity in all samples compared with dilution
      in saline alone. Peak signal intensities were at 0.625 and 1.25 mmol/L of
      gadolinium in iohexol at both magnet strengths. At 1.5 T, the addition of
      steroids and anesthetics to the saline solutions had no impact on the signal
      intensity curves, with the peak signal intensity at gadolinium concentrations of
      2.5 and 1.25 mmol/L. At 3.0 T, the addition of steroids and anesthetics had
      minimal effect on signal intensity curves, with the peak signal intensity at 1.25
      mmol/L of gadolinium. CONCLUSION: The addition of steroids and/or anesthetics to
      gadolinium solutions for MR arthrography does not substantially impact signal
      intensity. When gadolinium is diluted into a 50% or greater strength of iohexol,
      the signal intensity curve shifts so that the maximum signal intensity is
      obtained with lower gadolinium concentrations (0.625-1.25 mmol/L).

PMID- 24661250
TI  - Prediction of spontaneous preterm delivery in singleton pregnancies: where are we
      and where are we going? A review of literature.
AB  - Prematurity is the chief cause of neonatal morbidity and mortality. The objective
      of this study is to review the different methods for predicting preterm delivery
      in asymptomatic pregnant women and in situations of threatened preterm delivery.
      A search of the PubMed/Medline database was carried out for the years 1980-2012.
      We included studies for predicting preterm birth in asymptomatic and symptomatic
      patients. Models for predicting preterm delivery based on maternal factors,
      cervical length and obstetric history in first trimester of pregnancy is a
      valuable avenue of research. Nevertheless, prediction accuracy still needs to be
      improved. In the second and third trimesters, routine digital vaginal examination
      is of no value in asymptomatic women. Echography of the cervix is not useful
      except in patients with a history of late miscarriage or preterm delivery in
      order to offer them a preventive treatment. In symptomatic women, the combination
      of digital vaginal examination, cervical echography and fibronectin gives the
      best predictive results. Electromyography of the uterus and elastography of the
      cervix are interesting avenues for future research. Identifying patients at risk
      of preterm delivery should be considered differently at each stage of pregnancy.

PMID- 24661251
TI  - Evaluation of two Japanese regulatory actions using medical information
      databases: a 'Dear Doctor' letter to restrict oseltamivir use in teenagers, and
      label change caution against co-administration of omeprazole with clopidogrel.
AB  - WHAT IS KNOWN AND OBJECTIVE: The implementation of appropriate epidemiological
      methodology using medical information databases (MIDs) to evaluate the effects of
      regulatory actions has been highly anticipated. To assess scientific methods for
      active pharmacovigilance using MIDs, we conducted a quantitative assessment of
      the impact of two regulatory actions by the Japanese government: (i) restriction
      of use of oseltamivir in teenagers in March 2007 and (ii) caution against the co
      administration of omeprazole (OPZ) with clopidogrel (CPG) in April 2010. METHODS:
      Data were obtained from four hub hospitals in Japan. We measured the seasonal
      proportion of patients prescribed oseltamivir to those prescribed neuraminidase
      inhibitors for the 2002/2003 to 2010/2011 seasons. The monthly proportion of
      patients co-administered OPZ and CPG (OPZ+CPG) to those prescribed CPG was
      measured from May 2009 to April 2011. We evaluated the changes observed with
      implementation of the regulatory actions. To estimate the impact of the actions,
      we conducted segmented regression analysis using interrupted time series data.
      The impact was assessed by two parameter estimates of the regression model: the
      change in level for short-term effects and change in trend for long-term effects.
      RESULTS AND DISCUSSION: The use of oseltamivir in the target 10-19 years age
      group showed a significant and large decline (63.16%) immediately after the
      intervention (P = 0.0008). No change was observed in OPZ+CPG, although there was
      a relative inhibitory trend for OPZ+CPG compared with co-administration of
      lansoprazole or rabeprazole with CPG as the control group. When restricted to new
      users of CPG, the stratified results were consistent with the overall results.
      WHAT IS NEW AND CONCLUSION: The current analysis demonstrates the effectiveness
      of two regulatory actions. The results of the current study indicate that MID
      research can contribute to assessing and improving pharmacovigilance activities.

PMID- 24661253
TI  - Production of Monoclonal Antibody and Development of a New Immunoassay for
      Apramycin in Food.
AB  - Apramycin (APR) residue in food of animal origin can cause harmful effects on
      human health. In this study, a monoclonal antibody (mAb) was successfully
      produced using APR-BSA as immunogen, which was prepared by using the
      glutaraldehyde method. mAb 2A2 showed low cross-reactivity (<0.1%) with other
      aminoglycoside antibiotics, and its IC50 value was 0.35 ng/mL. On the basis of
      this mAb, a novel immunoassay in the format of an immunoaffinity test column
      (IATC) was developed. An immunoaffinity column filled with anti-APR antibody
      Sepharose 4B gel was used as solid phase. APR in sample and HRP-APR conjugate
      compete with each other for the limited antibody on the column. The approach was
      able to give a naked-eye color signal for the detection of analyte. A blue color
      appears for negative results and no color for positive. The method was then
      successfully applied to the detection of APR in animal-origin food. To further
      evaluate the assay, direct competitive ELISA (dcELISA) based on the same antibody
      was developed for comparison in different aspects. Compared to the dcELISA, the
      detection time of IATC is shortened to 20 min, whereas a similar sensitivity for
      various samples was observed. The limits of detection (LOD) for raw milk,
      muscles, and livers are 3 ng/mL, 3 MUg/kg, and 10 MUg/kg, respectively.

PMID- 24661252
TI  - Changes of urinary bladder contractility in high-fat diet-fed mice: the role of
      tumor necrosis factor-alpha.
AB  - OBJECTIVES: To study the role of tumor necrosis factor-alpha in bladder
      dysfunction associated with obesity. METHODS: Male 8-week-old C57BL/6J mice were
      divided into three groups: (i) control mice; (ii) vehicle-treated high-fat diet
      fed mice; and (iii) etanercept-treated high-fat diet-fed mice. High-fat diet
      feeding lasted for 12 weeks, vehicle or etanercept (0.8 mg/kg/day, a tumor
      necrosis factor-alpha antagonist) treatment was given during the last 4 weeks. At
      the end of the treatment period, serum tumor necrosis factor-alpha, total
      cholesterol, triglyceride and blood glucose were measured. Bladder strip
      contractile responses to 1 MUmol/L acetylcholine or 50 mmol/L KCl were studied in
      an organ bath. Bladder protein kinase Czeta, nuclear factor-kappaB and
      intercellular adhesion molecule-1 expressions were analyzed using western blots.
      RESULTS: Serum levels of tumor necrosis factor-alpha total cholesterol,
      triglyceride and glucose were significantly elevated in high-fat diet-fed mice;
      and the levels were not ameliorated by etanercept treatment. High-fat diet-fed
      mouse bladder showed reduced contractile responses to acetylcholine and KCl
      stimulation accompanied by high expression levels of phospho-protein kinase
      Czeta, nuclear nuclear factor-kappaB and intercellular adhesion molecule-1.
      Etanercept restored normal bladder contractile responses, as well as protein
      kinase Czeta nuclear factor-kappaB and intercellular adhesion molecule-1
      expressions. CONCLUSIONS: A high-fat diet induces bodyweight gain, hyperlipidemia
      and hyperglycemia in mice. Elevated serum tumor necrosis factor-alpha level
      associated with increased protein kinase Czeta phosphorylation, nuclear factor
      kappaB nuclear migration, intercellular adhesion molecule-1 expression and
      impaired muscle contractility are shown in the high-fat diet-fed mouse bladder.
      Tumor necrosis factor-alpha antagonist treatment restores normal bladder
      contractility, and protein kinase Czeta nuclear factor-kappaB and intercellular
      adhesion molecule-1 levels.

PMID- 24661254
TI  - Launching a wellness revolution at Spelman College.

PMID- 24661256
TI  - Incarcerated left diaphragmatic hernia following left hepatectomy for living
      donor liver transplantation.

PMID- 24661255
TI  - Hypoxic condition promotes differentiation and mineralization of dental pulp
      cells in vivo.
AB  - AIM: To investigate the behaviour of dental pulp cells under hypoxic conditions
      in vivo using an experimental animal model. METHODOLOGY: A mini-screw was
      inserted into the inferior dental nerve canal of rats to arrest the blood supply,
      which resulted in a reduced oxygen level in the dental pulps of molar teeth used
      for the experimental group. The decrease in blood supply was evaluated by
      injected India ink in transparent specimens. The hypoxia marker hypoxyprobe-1 was
      investigated by immunohistochemical staining. The mRNA expressions of ATP-binding
      cassette transporter (ABC) G2 (ABCG2) which is a marker for the capacity to
      excrete metabolites and for stem-like cells as well as dentine
      sialophosphoprotein (DSPP) and osteocalcin (OCN) which are markers for
      mineralization were evaluated by RT-PCR. Protein was evaluated by
      immunohistochemical staining using ABCG2, dentine sialoprotein (DSP) and OCN.
      RESULTS: The evaluation of India ink indicated a decreased blood supply in the
      transparent specimens, and hypoxyprobe-1 immunohistochemical staining showed
      positive expression. ABCG2, DSPP and OCN mRNA expressions increased at 7 and 14
      days. Immunohistochemically, ABCG2, DSP and OCN-positive cells were localized in
      the odontoblastic layer. CONCLUSIONS: Hypoxic conditions promoted mineralization
      and differentiation of dental pulp cells of the odontoblastic layer.

PMID- 24661257
TI  - In vitro generation of motor neuron precursors from mouse embryonic stem cells
      using mesoporous nanoparticles.
AB  - AIM: Stem cell-derived motor neurons (MNs) are utilized to develop replacement
      strategies for spinal cord disorders. Differentiation of embryonic stem cells
      into MN precursors involves factors and their repeated administration. We
      investigated if delivery of factors loaded into mesoporous nanoparticles could be
      effective for stem cell differentiation in vitro. MATERIALS & METHODS: We used a
      mouse embryonic stem cell line expressing green fluorescent protein under the
      promoter for the MN-specific gene Hb9 to visualize the level of MN
      differentiation. The differentiation of stem cells was evaluated by expression of
      MN-specific transcription factors monitored by quantitative real-time PCR
      reactions and immunocytochemistry. RESULTS: Mesoporous nanoparticles have strong
      affiliation to the embryoid bodies, penetrate inside the embryoid bodies and come
      in contact with differentiating cells. CONCLUSION: Repeated administration of
      soluble factors into a culture medium can be avoided due to a sustained release
      effect using mesoporous silica.

PMID- 24661258
TI  - Variations of the corona HDL:albumin ratio determine distinct effects of
      amorphous SiO2 nanoparticles on monocytes and macrophages in serum.
AB  - AIM: We investigated monocyte and macrophage death and cytokine production
      induced by amorphous silica nanoparticles (SiO2-NPs) to clarify the role of
      defined serum corona proteins. MATERIALS & METHODS: The cytotoxic proinflammatory
      effects of SiO2-NPs on human monocytes and macrophages were characterized in no
      serum, in fetal calf serum and in the presence of purified corona proteins.
      RESULTS: In no serum and in fetal calf serum above approximately 75 ug/ml, SiO2
      NPs lysed monocytes and macrophages by plasma membrane damage (necrosis). In
      fetal calf serum below approximately 75 ug/ml, SiO2-NPs triggered an
      endolysosomal acidification and caspase-1-dependent monocyte death (pyroptosis).
      The corona high-density lipoproteins:albumin ratio accounted for the features of
      the SiO2-NPs in serum. DISCUSSION: Corona high-density lipoproteins are a major
      determinant of the differential cytotoxic action of SiO2-NPs on monocytes and
      macrophages.

PMID- 24661259
TI  - Detection of denatonium benzoate (bitrex) remnants in noncommercial alcoholic
      beverages by Raman spectroscopy.
AB  - Illegal alcoholic beverages are often introduced into market using cheap
      technical alcohol, which is contaminated by denatonium benzoate (Bitrex) of very
      small concentration. Bitrex is the most bitter chemical compound and has to be
      removed before alcohol consumption. The home-made methods utilize sodium
      hypochlorite to disintegrate particles of denatonium benzoate in alcohol and to
      remove bitter taste before trading. In this experimental studies, we propose a
      novel method that detects in a fast way the remnants of denatonium benzoate in
      dubious alcohol samples by Raman spectroscopy. This method applies a portable
      Raman spectrometer of excitation wavelength 785 nm and utilizes the effect of
      surface-enhanced Raman spectroscopy (SERS) to recognize the suspected alcoholic
      beverages. High effectiveness (over 98%) of YES/NO classification of the
      investigated samples was observed when the nonlinear algorithm support vector
      machine (SVM) was exploited at carefully adjusted detection parameters. The
      method can identify illicit alcohol within minutes. 

PMID- 24661260
TI  - Global trade in exotic pets 2006-2012.
AB  - International trade in exotic pets is an important and increasing driver of
      biodiversity loss and often compromises the standards required for good animal
      welfare. We systematically reviewed the scientific and gray literature and used
      the United Nations Environment Programme - World Conservation Monitoring Centre
      (UNEP-WCMC) Convention on International Trade in Endangered Species of Wild Fauna
      and Flora (CITES) trade database to establish temporal and geographical trade
      patterns of live exotic birds, mammals, and reptiles and to describe trends in
      research, taxonomic representation, and level of threat and legal protection of
      species traded. Birds were the most species-rich and abundant class reported in
      trade; reptiles were second most abundant but unusually the most studied in this
      context; and mammals were least abundant in trade. Mammalian and reptilian
      species traded as pets were more likely to be threatened than expected by random.
      There have been a substantial number of Appendix I listed captive-bred mammals
      and birds and wild-caught birds and reptiles reported in trade to CITES. We
      identified the Middle East's emerging role as a driver of demand for exotic pets
      of all taxa alongside the well-established and increasing role of South America
      and Southeast Asia in the market. Europe, North America, and the Middle East
      featured most heavily in trade reports to CITES, whereas trade involving South
      America and Southeast Asia were given most emphasis in the literature. For
      effective monitoring of and appropriate response to the international exotic pet
      trade, it is imperative that the reliability and detail of CITES trade reports
      improve and that scientific research be directed toward those taxa and locations
      that are most vulnerable.

PMID- 24661261
TI  - Emerging drugs for allergic conjunctivitis.
AB  - INTRODUCTION: Allergic conjunctivitis (AC) is a very common disease, especially
      in association with allergic rhinitis but may also occur in isolated
      presentation. The treatment of AC has long been based on antihistamines, cromones
      and topical corticosteroids, but none of these drugs completely abolishes the
      clinical expression of AC. AREAS COVERED: The development of new drugs for AC is
      analyzed highlighting the recent insights into the pathophysiological mechanisms
      of the disease. The major aim of development of drugs for AC is to have agents
      able to prevent the inflammatory effects of the interaction between the allergen
      and the specific IgE antibodies on mast cell surface. This may be obtained by
      blocking the effects of histamine (the main mediator of early allergic response)
      by H1-receptor antagonists, inhibiting the release of soluble factors able to
      recruit inflammatory cells (that sustain prolonged inflammation) by mast-cell
      stabilizers, inhibiting the effects of single mediators, inducing tolerance to
      the allergen by specific immunotherapy or even acting on factors related to
      activation and differentiation of T lymphocytes such as the toll-like receptors.
      EXPERT OPINION: AC is an underestimated disease for which there is a search of
      more effective treatments. The availability of the drugs under current evaluation
      will allow more refined therapeutic strategies to apply according to the
      characteristics and the clinical severity of AC.

PMID- 24661262
TI  - Left atrial phasic function and mechanics in women with subclinical
      hypothyroidism: the effects of levothyroxine therapy.
AB  - BACKGROUND: Left atrial (LA) mechanics has been poorly investigated in women with
      subclinical hypothyroidism (SHT), and the effect of levothyroxine therapy on LA
      deformation and function is unknown. AIM: To investigate LA phasic function and
      mechanics assessed by two-dimensional echocardiography (2DE) and speckle tracking
      in women with SHT, and to estimate the influence of levothyroxine therapy on LA
      remodeling. METHODS: We included 48 untreated women with SHT and 38 healthy
      control women of the same age. All the SHT patients received levothyroxine
      therapy and were followed for 1 year after euthyroid status was achieved. All the
      participants underwent laboratory analyses and complete 2DE examination. RESULTS:
      Left atrial total emptying fraction was significantly lower in the SHT patients
      at the baseline in comparison with the controls. LA passive emptying fraction
      gradually decreased from the controls, throughout the treated SHT patients, to
      the untreated SHT patients. LA active emptying fraction was lower in the controls
      than in the untreated and the treated SHT participants. 2DE LA longitudinal
      strain and systolic strain rate gradually decreased from the controls to the
      untreated SHT patients, whereas LA early diastolic strain rate significantly
      increased in the same direction. Late diastolic LA strain was lower in the
      controls than in the untreated and the treated SHT patients. CONCLUSION:
      Subclinical hypothyroidism significantly affects LA mechanics. Reservoir,
      conduit, and booster pump LA functions are all impacted by SHT. A 1-year
      levothyroxine therapy significantly improves, but does not completely restore LA
      phasic function and mechanics in the SHT patients.

PMID- 24661263
TI  - Mental health service use among adolescents following participation in a
      randomized clinical trial for depression.
AB  - Major depressive disorder (MDD) is a common disorder among adolescents. The
      Treatment for Adolescents with Depression Study (TADS) was a randomized
      controlled trial to examine the efficacy of fluoxetine and cognitive-behavioral
      therapy (CBT), separately and together, compared with placebo, in adolescents 12
      to 17 years of age. The Survey of Outcomes Following Treatment for Adolescent
      Depression (SOFTAD) was designed as a naturalistic follow-up of participants in
      TADS. The aims of the current analyses are to describe mental health service use
      during the SOFTAD period. There were 196 adolescents recruited from 12 TADS
      sites. The Schedule for Affective Disorders and Schizophrenia for School-Age
      Children-Present and Lifetime Version was used for clinical diagnoses.
      Participants completed a psychiatric treatment log and the Child and Adolescent
      Services Assessment to assess service use. 58% received psychotherapy or
      nonstimulant psychotropic medication during SOFTAD. Youth with recurrent MDD had
      higher rates of treatment compared to youth without recurrent MDD (71% vs. 45%).
      However, nearly one third of the adolescents in the study did not receive
      treatment for a recurrent episode of depression. Service use differed by gender
      for those with recurrent MDD, with female participants (79%) receiving treatment
      at higher rates than male participants (55%), although there was no significant
      difference in depression severity between genders. Younger participants with
      recurrent MDD had higher odds of receiving psychotherapy. Use of psychotherapy
      and psychotropics following recurrence of depression appears to be influenced by
      age and gender. Even when youth respond well to treatment, a sizeable percentage
      are likely to experience a subsequent episode that may go untreated. 

PMID- 24661264
TI  - Urine and plasma metabolites predict the development of diabetic nephropathy in
      individuals with Type 2 diabetes mellitus.
AB  - AIMS: Early detection of individuals with Type 2 diabetes mellitus or
      hypertension at risk for micro- or macroalbuminuria may facilitate prevention and
      treatment of renal disease. We aimed to discover plasma and urine metabolites
      that predict the development of micro- or macroalbuminuria. METHODS: Patients
      with Type 2 diabetes (n = 90) and hypertension (n = 150) were selected from the
      community-cohort 'Prevention of REnal and Vascular End-stage Disease' (PREVEND)
      and the Steno Diabetes Center for this case-control study. Cases transitioned in
      albuminuria stage (from normo- to microalbuminuria or micro- to
      macroalbuminuria). Controls, matched for age, gender, and baseline albuminuria
      stage, remained in normo- or microalbuminuria stage during follow-up. Median
      follow-up was 2.9 years. Metabolomics were performed on plasma and urine. The
      predictive performance of a metabolite for albuminuria transition was assessed by
      the integrated discrimination index. RESULTS: In patients with Type 2 diabetes
      with normoalbuminuria, no metabolites discriminated cases from controls. In
      patients with Type 2 diabetes with microalbuminuria, plasma histidine was lower
      (fold change = 0.87, P = 0.02) and butenoylcarnitine was higher (fold change =
      1.17, P = 0.007) in cases vs. controls. In urine, hexose, glutamine and tyrosine
      were lower in cases vs. controls (fold change = 0.20, P < 0.001; 0.32, P < 0.001;
      0.51, P = 0.006, respectively). Adding the metabolites to a model of baseline
      albuminuria and estimated glomerular filtration rate metabolites improved risk
      prediction for macroalbuminuria transition (plasma integrated discrimination
      index = 0.28, P < 0.001; urine integrated discrimination index = 0.43, P <
      0.001). These metabolites did not differ between hypertensive cases and controls
      without Type 2 diabetes. CONCLUSIONS: Type 2 diabetes-specific plasma and urine
      metabolites were discovered that predict the development of macroalbuminuria
      beyond established renal risk markers. These results should be confirmed in a
      large, prospective cohort.

PMID- 24661265
TI  - The use of polypropylene suture as a frontalis suspension material in all age
      groups of ptosis patients.
AB  - PURPOSE/AIM: To evaluate the use of 2-0 polypropylene suture for frontal
      suspension in ptosis patients with poor levator function. MATERIALS AND METHODS:
      This retrospective study included 20 eyelids of 16 patients (5 female, 11 male)
      with 4 mm or less levator function. The operation was considered successful when
      the difference between the two upper lids was <= 1 mm, and the upper lid covered
      the upper limbus by <3 mm. RESULTS: Median patient age was 22.94 years (2 to 59).
      Mean follow-up time was 18.06 months (12-29). A successful result was obtained in
      14 patients (87.5%). Ptosis recurrence was observed in two patients (12.5%).
      Lagophthalmos with punctate epithelial keratitis and subsequent spontaneous
      recovery occurred during the first postoperative week in six patients (37.5%).
      Two patients with hypocorrection underwent revision surgery in the first
      postoperative week. Granuloma and material exposition at the forehead incision
      site observed in one patient at the postoperative fifth month were repaired by
      excision of the granuloma and suture reposition. CONCLUSIONS: Polypropylene
      suture as a frontalis suspension material in ptosis patients with poor levator
      function maintained satisfactory results at follow-up. This material allows easy
      and repeatable eyelid height adjustment and does not obviate future eyelid
      procedures.

PMID- 24661267
TI  - Sexual life of Japanese patients with erectile dysfunction taking
      phosphodiesterase type 5 inhibitors: an Internet survey using the Psychological
      and Interpersonal Relationship Scales-Short Form questionnaire.
AB  - OBJECTIVES: To investigate details of sexual function of erectile dysfunction in
      Japanese patients taking phosphodiesterase type 5 inhibitors. METHODS: A Japanese
      version of the Psychological and Interpersonal Relationship Scales-Short Form was
      used to carry out a nationwide survey using the Internet. A total of 556 erectile
      dysfunction patients (age 30-70 years) who had been prescribed a
      phosphodiesterase type 5 inhibitor and had attempted sexual intercourse within
      the past 6 months were included in this survey. Scores were compared in relation
      to the phosphodiesterase type 5 inhibitors most frequently taken within the past
      6 months. RESULTS: In the subdomains of self-confidence and spontaneity of the
      Psychological and Interpersonal Relationship Scales-Short Form, scores for
      vardenafil and tadalafil were significantly higher than those for sildenafil. In
      the subdomain of time concern of the Psychological and Interpersonal Relationship
      Scales-Short Form, the score for tadalafil was significantly lower than that for
      others. CONCLUSIONS: Our findings support the hypothesis that Japanese patients
      with erectile dysfunction have high sexual self-confidence, spontaneity and low
      time concerns when taking tadalafil. These characteristics of tadalafil could be
      associated with high patient satisfaction and high preference.

PMID- 24661266
TI  - Triazine-based tool box for developing peptidic PET imaging probes: syntheses,
      microfluidic radiolabeling, and structure-activity evaluation.
AB  - This study was aimed at developing a triazine-based modular platform for targeted
      PET imaging. We synthesized mono- or bis-cyclo(RGDfK) linked triazine-based
      conjugates specifically targeting integrin alphavbeta3 receptors. The core
      molecules could be easily linked to targeting peptide and radiolabeled
      bifunctional chelator. The spacer core molecule was synthesized in 2 or 3 steps
      in 64-80% yield, and the following conjugation reactions with cyclo(RGDfK)
      peptide or bifunctional chelator were accomplished using "click" chemistry or
      amidation reactions. The DOTA-TZ-Bis-cyclo(RGDfK) 13 conjugate was radiolabeled
      successfully with (64)Cu(OAc)2 using a microfluidic method, resulting in higher
      specific activity with above 95% labeling yields compared to conventional
      radiolabeling (SA ca. 850 vs 600 Ci/mmol). The dimeric cyclo(RGDfK) peptide was
      found to display significant bivalency effect using I(125)-Echistatin binding
      assay with IC50 value as 178.5 +/- 57.1 nM, which displayed a 3.6-fold
      enhancement of binding affinity compared to DOTA-TZ-cyclo(RGDfK) 14 conjugate on
      U87MG human glioblastoma cell. Biodistribution of all four conjugates in female
      athymic nude mice were evaluated. DOTA-"Click"-cyclo(RGDfK) 15 had the highest
      tumor uptake among these four at 4 h p.i. with 1.90 +/- 0.65%ID/g, while there
      was no clear bivalency effect for DOTA-TZ-BisRGD in vivo, which needs further
      experiments to address the unexpected questions. 

PMID- 24661268
TI  - Multivalent macromolecules redirect nucleation-dependent fibrillar assembly into
      discrete nanostructures.
AB  - Manipulating the size and shape of noncovalent multivalent assemblies is an
      ongoing challenge in the field of supramolecular polymers. Following a
      mechanistic approach, we reasoned that nucleation-elongation kinetics presents
      unique opportunities for controlled growth since the final outcome is likely to
      depend on the structure and dynamics of critical-nucleus formation. Taking
      fibrillar assembly of amyloid beta (Abeta) peptide as the model system of
      nucleation-dependent supramolecular polymerization, here we report multivalent
      polymer-peptide conjugates (mPPCs) that redirect fibrillar assembly of Abeta to
      form discrete nanostructures. The mPPCs were rationally designed to target Abeta
      intermediates formed prior to critical nucleation. Atomic force microscopy and
      transmission electron microscopy studies show that in the presence of mPPCs,
      Abeta self-assembles into zero-dimensional discrete nanostructures with lateral
      dimensions approximately in 5-35 nm, while Abeta alone self-assembles into one
      dimensional fibrils in micrometer. Thioflavin T kinetics fluorescence assays
      demonstrate that mPPCs suppress Abeta fibrillogenesis. The mPPCs may thus
      represent a prototypical molecular design of multivalent macromolecules able to
      control the final shape of supramolecular polymers assembled via a nucleation
      dependent mechanism. 

PMID- 24661269
TI  - Understanding interactions between manganese oxide and gold that lead to enhanced
      activity for electrocatalytic water oxidation.
AB  - To develop active nonprecious metal-based electrocatalysts for the oxygen
      evolution reaction (OER), a limiting reaction in several emerging renewable
      energy technologies, a deeper understanding of the activity of the first row
      transition metal oxides is needed. Previous studies of these catalysts have
      reported conflicting results on the influence of noble metal supports on the OER
      activity of the transition metal oxides. Our study aims to clarify the
      interactions between a transition metal oxide catalyst and its metal support in
      turning over this reaction. To achieve this goal, we examine a catalytic system
      comprising nanoparticulate Au, a common electrocatalytic support, and
      nanoparticulate MnO(x), a promising OER catalyst. We conclusively demonstrate
      that adding Au to MnO(x) significantly enhances OER activity relative to MnO(x)
      in the absence of Au, producing an order of magnitude higher turnover frequency
      (TOF) than the TOF of the best pure MnO(x) catalysts reported to date. We also
      provide evidence that it is a local rather than bulk interaction between Au and
      MnO(x) that leads to the observed enhancement in the OER activity. Engineering
      improvements in nonprecious metal-based catalysts by the addition of Au or other
      noble metals could still represent a scalable catalyst as even trace amounts of
      Au are shown to lead a significant enhancement in the OER activity of MnO(x).

PMID- 24661270
TI  - Meta-analysis of attitudes toward damage-causing mammalian wildlife.
AB  - Many populations of threatened mammals persist outside formally protected areas,
      and their survival depends on the willingness of communities to coexist with
      them. An understanding of the attitudes, and specifically the tolerance, of
      individuals and communities and the factors that determine these is therefore
      fundamental to designing strategies to alleviate human-wildlife conflict. We
      conducted a meta-analysis to identify factors that affected attitudes toward 4
      groups of terrestrial mammals. Elephants (65%) elicited the most positive
      attitudes, followed by primates (55%), ungulates (53%), and carnivores (44%).
      Urban residents presented the most positive attitudes (80%), followed by
      commercial farmers (51%) and communal farmers (26%). A tolerance to damage index
      showed that human tolerance of ungulates and primates was proportional to the
      probability of experiencing damage while elephants elicited tolerance levels
      higher than anticipated and carnivores elicited tolerance levels lower than
      anticipated. Contrary to conventional wisdom, experiencing damage was not always
      the dominant factor determining attitudes. Communal farmers had a lower
      probability of being positive toward carnivores irrespective of probability of
      experiencing damage, while commercial farmers and urban residents were more
      likely to be positive toward carnivores irrespective of damage. Urban residents
      were more likely to be positive toward ungulates, elephants, and primates when
      probability of damage was low, but not when it was high. Commercial and communal
      farmers had a higher probability of being positive toward ungulates, primates,
      and elephants irrespective of probability of experiencing damage. Taxonomic bias
      may therefore be important. Identifying the distinct factors explaining these
      attitudes and the specific contexts in which they operate, inclusive of the
      species causing damage, will be essential for prioritizing conservation
      investments.

PMID- 24661271
TI  - Osmotic stress affects the stability of freeze-dried Lactobacillus buchneri R1102
      as a result of intracellular betaine accumulation and membrane characteristics.
AB  - AIMS: To help cells to better resist the stressful conditions associated with the
      freeze-drying process during starter production, we investigated the effect of
      various osmotic conditions on growth, survival and acidification activity of
      Lactobacillus buchneri R1102, after freeze-drying and during storage for 3 months
      at 25 degrees C. METHODS AND RESULTS: High survival rates during freeze-drying,
      but not during storage, were obtained when 0.1 mol l(-1) KCl was added at the
      beginning of fermentation, without any change in membrane properties and betaine
      accumulation. This condition made it possible to maintain a high acidification
      rate throughout the process. In contrast, the addition of 0.6 mol l(-1) KCl
      concentrations at the beginning of fermentation led to a high survival rate
      during storage that was related to high intracellular betaine levels, low
      membrane fluidity and high cycC19:0 concentrations. However, these modifications
      induced the degradation of acidification activity during storage. When a moderate
      stress was applied by combining 0.1 mol l(-1) KCl at the beginning and 0.6 mol l(
      1) KCl at the end of fermentation, betaine accumulated in the cells without any
      membrane alteration, allowing them to maintain high acidification activity and
      survival rate during storage. CONCLUSION: Specific osmotic conditions during
      fermentation induced intracellular betaine accumulation and modifications of
      membrane character-istics, thus affecting stress resistance of Lact. buchneri
      R1102. A slight osmotic stress made it possible to maintain a high acidification
      activity, whereas a high osmotic stress at the end of fermentation led to the
      preservation of cell survival during freeze-dried storage. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study revealed that the survival and preservation of
      acidification activity of freeze-dried Lact. buchneri R1102 during starter
      production can be improved by using appropriate osmotic conditions.

PMID- 24661272
TI  - The global epidemiology and burden of opioid dependence: results from the global
      burden of disease 2010 study.
AB  - AIMS: To estimate the prevalence and burden of disease attributable to opioid
      dependence globally, regionally and at country level. METHODS: Multiple search
      strategies: (i) peer-reviewed literature searches; (ii) systematic searches of
      online databases; (iii) internet searches; (iv) consultation and feedback from
      experts. Culling and data extraction followed protocols. DisMod-MR, the latest
      version of the generic disease modelling system, a Bayesian meta-regression tool,
      imputed prevalence by age, year and sex for 187 countries and 21 regions.
      Disability weight for opioid dependence was estimated through population surveys
      and multiplied by prevalence data to calculate the years of life lived with
      disability (YLDs). Opioid dependence premature mortality was computed as years of
      life lost (YLLs) and summed with YLDs to calculate disability-adjusted life years
      (DALYs). RESULTS: There were 15.5 million opioid-dependent people globally in
      2010 [0.22%, 95% uncertainty interval (UI) = 0.20-0.25%]. Age-standardized
      prevalence was higher in males (0.30%, 95% UI = 0.27-0.35%) than females (0.14%,
      95% UI = 0.12-0.16%), and peaked at 25-29 years. Prevalence was higher than the
      global pooled prevalence in Australasia (0.46%, 95% UI = 0.41-0.53%), western
      Europe (0.35%, 95% UI = 0.32-0.39) and North America (0.30%, 95% UI = 0.25-0.36).
      Opioid dependence was estimated to account for 9.2 million DALYs globally (0.37%
      of global DALYs) in 2010, a 73% increase on DALYs estimated in 1990. Regions with
      the highest opioid dependence DALY rates were North America (292.1 per 100,000),
      eastern Europe (288.4 per 100,000), Australasia (278.6 per 100,000) and southern
      sub-Saharan Africa (263.5 per 100,000). The contribution of YLLs to opioid
      dependence burden was particularly high in North America, eastern Europe and
      southern sub-Saharan Africa. CONCLUSION: Opioid dependence is a substantial
      contributor to the global disease burden; its contribution to premature mortality
      (relative to prevalence) varies geographically, with North America, eastern
      Europe and southern sub-Saharan Africa most strongly affected.

PMID- 24661273
TI  - Editorial comment from Dr Miyata to Functional polymorphisms in the matrix
      metalloproteinase genes and their association with bladder cancer risk and
      recurrence: a mini-review.

PMID- 24661274
TI  - [When do bad apples not spoil the barrel? Negative relationships in teams, team
      performance, and buffering mechanisms].
AB  - The study of negative relationships in teams has primarily focused on the impact
      of negative relationships on individual team member attitudes and performance in
      teams. The mechanisms and contingencies that can buffer against the damaging
      effects of negative relationships on team performance have received limited
      attention. Building on social interdependence theory and the multilevel model of
      team motivation, we examine in a sample of 73 work teams the team-level
      attributes that foster the promotive social interaction that can neutralize the
      adverse effect of negative relationships on team cohesion and, consequently, on
      team performance. The results indicate that high levels of team-member exchange
      as well as high task-interdependence attenuate how team cohesion and team
      performance suffer from negative relationships. Implications for research and
      practice are discussed.

PMID- 24661275
TI  - Members' needs, intragroup conflict, and group performance.
AB  - Focusing on "what people want in their group" as a critical antecedent of
      intragroup conflict, the present study theorizes and empirically investigates the
      relationships among the psychological needs of group members, intragroup
      conflict, and group performance. It attends to the within-group average and
      dispersion of members' psychological needs and examines the effects stemming from
      group composition of needs on multiple types of conflict. The analyses based on
      multisource data from 145 organizational teams revealed significant relationships
      between the groups' composition with respect to the members' need for achievement
      and task conflict, need for affiliation and relationship conflict, and need for
      power and status conflict. Some of these relationships were moderated by open
      communication among members. The analyses also demonstrated that when the 3 types
      of conflict were considered together, task conflict was a positive predictor of
      group performance, whereas relationship conflict was a negative predictor. The
      findings highlight the motivational aspects of intragroup conflict, revealing the
      multilevel dynamics of the psychological needs in social settings.

PMID- 24661276
TI  - Testing the generalizability of indirect range restriction corrections.
AB  - Range restriction is a common problem in personnel selection and other contexts
      in applied psychology. For many years researchers have used corrections that
      assume range restriction was direct, even when it was known that range
      restriction was indirect. Hunter, Schmidt, and Le (2006) proposed a new
      correction for cases of indirect range restriction that greatly increases its
      potential usefulness due to its reduced information requirements compared to
      alternatives. The current study examines the applicability of Hunter et al.'s
      correction to settings where its assumed structural model is violated by
      including the measures that are to be involved in corrections in the original
      selection composite. We conclude that Hunter et al.'s correction should generally
      be preferred when compared to its common alternative, Thorndike's Case II
      correction for direct range restriction. However, this is due to the likely
      violation of one of the other assumptions of the Hunter et al. correction in most
      applied settings. Correction mechanisms and practical implications are discussed.

PMID- 24661277
TI  - The burden of white matter hyperintensities is a predictor of progressive mild
      cognitive impairment in patients with Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: To evaluate whether white matter hyperintensities (WMHs)
      may act as an independent predictor for progression of cognitive status, the
      authors analyzed the longitudinal effects of WMHs on cognitive dysfunction in non
      demented patients with Parkinson's disease (PD). METHODS: A total of 111 patients
      with PD were enrolled, including subjects with mild cognitive impairment (MCI, n
      = 65) and cognitively normal subjects (CN, n = 46). These individuals were
      classified as MCI converters (n = 22) or MCI non-converters (n = 43) and CN
      converters (n = 18) or CN non-converters (n = 28) based on whether they were
      subsequently diagnosed with PD dementia or PD-MCI during a minimum 24-month
      follow-up. The WMH burden and the Cholinergic Pathway Hyperintensities Scale
      (CHIPS) and their relationships to longitudinal changes in cognitive performance
      were examined. RESULTS: PD-MCI converters had larger WMH volume (14421.0 vs.
      5180.4, P < 0.001) and higher CHIPS score (22.6 vs. 11.2, P = 0.001) compared
      with PD-MCI non-converters. Logistic regression analysis revealed in patients
      with PD-MCI that WMH volume (odds ratio 1.616, P = 0.009) and CHIPS score (odds
      ratio 1.084, P = 0.007) were independently associated with PD dementia
      conversion. However, WMH volume and CHIPS score did not differ between PD-CN
      converters and PD-CN non-converters. In patients with PD-MCI, both WMH volume and
      CHIPS score were closely associated with longitudinal decline in general
      cognition, semantic fluency and Stroop test scores. CONCLUSIONS: The present
      study demonstrates that WMH burden is a significant predictor of conversion from
      PD-MCI to PD dementia and is related to ongoing decline in frontal-lobe-based
      cognitive performance.

PMID- 24661278
TI  - How to create a 'writing tool box' for scholars writing in English as a second
      language.

PMID- 24661279
TI  - Older Japanese primiparas' experiences at the time of their post-delivery
      hospital stay.
AB  - The purpose of this study was to gain a deeper understanding of the postpartum
      experiences of older primiparas at the time of their postpartum hospital stay.
      Participants were Japanese primiparas aged 35-44 years who gave birth, without
      abnormalities for either the mother or child. Data were obtained using a semi
      structured interview with 22 participants. Thirteen themes emerged through
      content analysis. We found that there were distinctive experiences, which
      included 'the health and growth of the baby: relief and continued anxiety',
      'awareness of strengths and of concerns of primiparas', 'meaning of the pregnancy
      and childbirth experience' and 'developing one's own child-care approach'.
      Findings suggest that nursing care during the post-delivery hospital stay should
      use the unique strengths of older primiparas to enable their smooth transition to
      maternal role attainment. 

PMID- 24661280
TI  - Postpartum experiences of older Japanese primiparas during the first month after
      childbirth.
AB  - This study aimed to describe the postpartum experiences of older Japanese
      primiparas during the first month after childbirth. The participants were 21
      primiparous women over 35 years of age who gave birth to a healthy child at three
      urban hospitals. Data were collected from July 2011 to April 2012 through a semi
      structured interview about postpartum experiences after discharge. Data were
      analysed using content analysis. We obtained Institutional Review Boards'
      approval and written informed consent from all participants prior to study
      initiation. Thirteen themes of postpartum experiences were extracted. The
      findings revealed that the mothers' experiences varied greatly and were highly
      personal. Also, participants described common experiences, unique child-care
      support needs and the strengths of older primiparas. Understanding the postpartum
      experiences of older primiparas assists health-care professionals to identify
      better ways to provide appropriate support. 

PMID- 24661281
TI  - Life-space mobility and social support in elderly adults with orthopaedic
      disorders.
AB  - The purpose of this cross-sectional survey was to explore relationships between
      life-space mobility and the related factors in elderly Japanese people who attend
      orthopaedic clinics. The study measures included surveys of life-space mobility
      (Life-space Assessment (LSA) score), social support (social network diversity and
      social ties), physical ability (instrumental self-maintenance, intellectual
      activity, social role), orthopaedic factors (diseases and symptoms) and
      demographic information. The questionnaire was distributed to 156 subjects; 152
      persons responded, yielding 140 valid responses. Mean age of the sample was 76.0
      +/- 6.4 (range, 65-96 years), with 57.9% women (n = 81). In a multiple regression
      analysis, the six factors were significantly associated with LSA. Standardized
      partial regression coefficients (beta) were gender (0.342), instrumental self
      maintenance (0.297), social network diversity (0.217), age (-0.170), difficulty
      of motion (-0.156) and intellectual activity (0.150), with an adjusted R(2) =
      0.488. These results suggest that outpatient health-care providers need to
      intervene in not only addressing orthopaedic factors but also promoting social
      support among elderly Japanese.

PMID- 24661282
TI  - Who provides nursing services in Cambodian hospitals?
AB  - In Cambodia, the number of nurses is insufficient and details of nursing services
      are unknown and undocumented. This research explored who provides nursing service
      activities in Cambodia. The study was conducted at nine hospitals in Cambodia.
      Findings indicate that non-invasive medical care such as vital signs taking was
      designated to nurses. In performing more complex medical interventions, nurses
      shared the tasks with medical doctors. Conversely, simpler nursing tasks,
      including maintaining bedside environment/hygiene and supporting patient
      activities, tasks were shared by nurses with patients' family. This study
      elucidated an optimal personnel mix and task shared between nurses, doctors and
      patients' families. There are important implications for nursing legislation
      related to streamlining the production of nurses to provide an adequate and
      qualified nursing service in Cambodia. 

PMID- 24661284
TI  - A unique Ni2+ -dependent and methylglyoxal-inducible rice glyoxalase I possesses
      a single active site and functions in abiotic stress response.
AB  - The glyoxalase system constitutes the major pathway for the detoxification of
      metabolically produced cytotoxin methylglyoxal (MG) into a non-toxic metabolite D
      lactate. Glyoxalase I (GLY I) is an evolutionarily conserved metalloenzyme
      requiring divalent metal ions for its activity: Zn(2+) in the case of eukaryotes
      or Ni(2+) for enzymes of prokaryotic origin. Plant GLY I proteins are part of a
      multimember family; however, not much is known about their physiological
      function, structure and metal dependency. In this study, we report a unique GLY I
      (OsGLYI-11.2) from Oryza sativa (rice) that requires Ni(2+) for its activity. Its
      biochemical, structural and functional characterization revealed it to be a
      monomeric enzyme, possessing a single Ni(2+) coordination site despite containing
      two GLY I domains. The requirement of Ni(2+) as a cofactor by an enzyme involved
      in cellular detoxification suggests an essential role for this otherwise toxic
      heavy metal in the stress response. Intriguingly, the expression of OsGLYI-11.2
      was found to be highly substrate inducible, suggesting an important mode of
      regulation for its cellular levels. Heterologous expression of OsGLYI-11.2 in
      Escherichia coli and model plant Nicotiana tabacum (tobacco) resulted in improved
      adaptation to various abiotic stresses caused by increased scavenging of MG,
      lower Na(+) /K(+) ratio and maintenance of reduced glutathione levels. Together,
      our results suggest interesting links between MG cellular levels, its
      detoxification by GLY I, and Ni(2+) - the heavy metal cofactor of OsGLYI-11.2, in
      relation to stress response and adaptation in plants.

PMID- 24661285
TI  - Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, alpha
      phellandrene, and essential oil from Schinus terebinthifolius fruits in a
      neuropathic pain model.
AB  - OBJECTIVES: Previous studies have shown that essential oil containing (R)-(+)
      limonene and alpha-phellandrene, extracted from fruits of Schinus
      terebinthifolius Raddi, exhibit anti-inflammatory activity. This work aimed to
      verify the antihyperalgesic and antidepressive actions of (R)-(+)-limonene, alpha
      phellandrene, and essential oil from S. terebinthifolius fruits in spared nerve
      injury (SNI) model of neuropathic pain in rats. METHODS: In the present work,
      essential oil from fruits of S. terebinthifolius, as well as the pure (R)-(+)
      limonene and alpha-phellandrene compounds, were assayed for their effects on SNI
      induced mechanical and cold hyperalgesia, and depressive-like behavior
      (immobility in forced swim test) in rats. The locomotor activity was evaluated in
      open-field test. RESULTS: Oral administration for up to 15 days of essential oil
      of S. terebinthifolius (100 mg/kg), (R)-(+)-limonene (10 mg/kg), alpha
      phellandrene (10 mg/kg), and also subcutaneous 10 mg/kg dose of ketamine
      (positive control) significantly inhibited SNI-induced mechanical hyperalgesia
      and increased immobility in the forced swim test. On the 15th day of oral
      treatment, alpha-phellandrene, but neither the essential oil from S.
      terebinthifolius nor (R)-(+)-limonene, prevented the SNI-induced increase in
      sensitivity to a cold stimulus. The oral treatment with essential oil (100 mg/kg)
      or with compounds (10 mg/kg) did not interfere on locomotor activity. DISCUSSION:
      Together, the results of the present work show that essential oil of S.
      terebinthifolius and compounds present in this oil, including (R)-(+)-limonene
      and alpha-phellandrene, exhibit antihyperalgesic effects against mechanical
      hyperalgesia, and are antidepressive, while only alpha-phellandrene inhibited
      cold hyperalgesia in SNI rats.

PMID- 24661287
TI  - Analysis of nitrites and nitrates in hams and sausages by open-tubular capillary
      electrochromatography with a nanolatex-coated capillary column.
AB  - In this work, a new open-tubular capillary electrochromatography (OT-CEC) method
      with the nanolatex-coated column was proposed for the determination of nitrites
      and nitrates in foodstuffs. The method was simple and repeatable as a result of
      avoiding the introduction of an electroosmotic flow reverse additive (such as
      cetyltrimethylammonium chloride) in electrophoretic buffer. The limits of
      quantitation were 0.89 and 1.05 mg kg-1 for nitrate and nitrite, respectively,
      whereas the overall recoveries ranged from 94 to 103%. The developed OT-CEC
      method was successfully applied for 12 samples, and the residue profiles of
      nitrites and nitrates in hams and sausages were obtained and evaluated.

PMID- 24661286
TI  - Emerging therapeutic targets for synovial sarcoma.
AB  - Synovial sarcoma is part of soft tissue sarcomas, an uncommon group of malignant
      tumors of mesenchymal origin. Unfortunately, a very limited number of useful
      drugs are active for most advanced synovial sarcoma. These tumors showed VEGF
      expression, and elevated serum VEGF levels correlate with higher histologic tumor
      grade. Inhibition of VEGFR was associated with tumor activity in preclinical
      models of synovial sarcoma and drugs such as sorafenib, pazopanib and bevacizumab
      have been employed in synovial sarcoma in monotherapy and in combination with
      chemotherapy. Other targets such as EGFR, HER2, IGFR-1R and mTOR have been
      exploited, but their inhibition by drugs such as gefitinib, trastuzumab,
      figitumumab, and temsirolimus, has not resulted in meaningful activity. Newer
      approaches include CXCR4 inhibition, immune-based therapies (NY-ESO-1), targeting
      epigenetic misregulation with HDAC inhibitors and targeting developmental
      pathways such Notch and Hedgehog. This review will summarize achievements and
      pitfalls of drugs against emerging therapeutic targets for synovial sarcoma. 

PMID- 24661288
TI  - Callous-unemotional behavior and early-childhood onset of behavior problems: the
      role of parental harshness and warmth.
AB  - Youth with callous-unemotional (CU) behavior are at risk of developing more
      severe forms of aggressive and antisocial behavior. Previous cross-sectional
      studies suggest that associations between parenting and conduct problems are less
      strong when children or adolescents have high levels of CU behavior, implying
      lower malleability of behavior compared to low-CU children. The current study
      extends previous findings by examining the moderating role of CU behavior on
      associations between parenting and behavior problems in a very young sample, both
      concurrently and longitudinally, and using a variety of measurement methods. Data
      were collected from a multi-ethnic, high-risk sample at ages 2 to 4 (N = 364; 49%
      female). Parent-reported CU behavior was assessed at age 3 using a previously
      validated measure (Hyde et al., 2013 ). Parental harshness was coded from
      observations of parent-child interactions and parental warmth was coded from 5
      min speech samples. In this large and young sample, CU behavior moderated cross
      sectional correlations between parent-reported and observed warmth and child
      behavior problems. However, in cross-sectional and longitudinal models testing
      parental harshness, and longitudinal models testing warmth, there was no
      moderation by CU behavior. The findings are in line with recent literature
      suggesting parental warmth may be important to child behavior problems at high
      levels of CU behavior. In general, however, the results of this study contrast
      with much of the extant literature and suggest that in young children, affective
      aspects of parenting appear to be related to emerging behavior problems,
      regardless of the presence of early CU behavior.

PMID- 24661289
TI  - Isolated tricuspid valve repair for Libman-Sacks endocarditis.
AB  - Cardiac involvement is a well-known complication of systemic lupus erythematosus
      (SLE), which can involve most cardiac components, including pericardium,
      conduction system, myocardium, heart valves, and coronary arteries. Libman-Sacks
      (verrucous) endocarditis is the characteristic cardiac valvular manifestation.
      Although isolated tricuspid valve involvement is quite rare, we report a patient
      with SLE who had tricuspid stenosis caused by Libman-Sacks endocarditis. The
      patient underwent successful commisurotomy and Kay annuloplasty on the tricuspid
      valve under cardiopulmonary bypass. 

PMID- 24661290
TI  - Pharmacokinetic modelling of serum and bronchial concentrations for
      clarithromycin and telithromycin, and site-specific pharmacodynamic simulation
      for their dosages.
AB  - WHAT IS KNOWN AND OBJECTIVE: Clinical pharmacokinetic profiles of clarithromycin
      and telithromycin in bronchopulmonary sites have not been fully characterized.
      This study aimed to describe in more detail the pharmacokinetics of the two
      macrolides in epithelial lining fluid (ELF) of human bronchi and to evaluate
      their pharmacodynamic target attainment at this site. METHODS: Previously
      reported drug concentration data for serum and ELF were simultaneously fitted to
      a three-compartment pharmacokinetic model using nonmem program. The model
      parameter estimates were used for site-specific pharmacodynamic simulation.
      RESULTS AND DISCUSSION: Population mean parameters for clarithromycin were as
      follows: distribution volumes of central, peripheral and ELF compartments (V1 /F,
      V2 /F and V3 /F) = 204.7, 168.9 and 67.1 L; clearance (CL/F) = 34.4 L/h;
      absorption rate constant (Ka ) = 0.680 1/h; transfer rate constants connecting
      compartments (K12 , K21 , K13 and K31  = 0.0193, 0.434, 0.667 and 0.260 1/h,
      respectively). Mean parameters for telithromycin were as follows: V1 /F, V2 /F
      and V3 /F = 370.3, 290.3 and 213.8 L; CL/F = 89.5 L/h; Ka  = 0.740 1/h; K12 , K21
      , K13 and K31  = 0.0026, 1.044, 0.758 and 0.158 1/h, respectively. Using these
      parameters, the mean ELF/serum ratio in the area under drug concentration-time
      curve (AUC) was 7.80 for clarithromycin and 8.05 for telithromycin.
      Clarithromycin achieved a >= 90% probability of attaining a pharmacodynamic
      target [AUC/minimum inhibitory concentration (MIC) = 100] in ELF against
      bacterial isolates for which MICs were <=0.5 and <=1 mg/L for twice-daily doses
      of 250 and 500 mg, respectively. For telithromycin, once-daily doses of 600 and
      800 mg achieved a >=90% probability in ELF against Streptococcus pneumoniae,
      Staphylococcus aureus and Moraxella catarrhalis isolates but not Haemophilus
      influenzae isolates. WHAT IS NEW AND CONCLUSION: These results should provide a
      better understanding of the bronchial pharmacokinetics of clarithromycin and
      telithromycin, while also providing useful information about their dosages for
      respiratory tract infections based on site-specific pharmacodynamic evaluation.
      Further studies in a large number of patients are needed to confirm our findings
      and clarify their therapeutic implications.

PMID- 24661291
TI  - The National Council on Radiation Protection and Measurements: a growing
      structure.

PMID- 24661296
TI  - Case 204: Nonketotic hyperglycemia-induced hemiballism-hemichorea.
AB  - HISTORY: An 87-year-old white woman presented to our emergency department with a
      2-day history of involuntary movements of the right upper and lower extremities.
      The movements increased with action, decreased with relaxation, and disappeared
      during sleep. The patient's medical history included diabetes mellitus type 2,
      congestive heart failure, and hypertension. No history of parkinsonism or other
      neurologic disorders was reported. Furthermore, the patient had no prior history
      of dopamine antagonist or estrogen medication use. At admission, she was fully
      alert and oriented. A physical examination revealed her muscle tone and strength
      were normal on both sides; however, she reported transient weakness in the right
      limbs. There was no evidence of sensory impairment, and cranial nerves were
      normal. The deep tendon reflexes were symmetrically hypoactive. Her skin was
      pink, warm, and dry. Laboratory tests revealed poorly controlled diabetes
      mellitus, with a fasting blood glucose level of 410 mg/dL (22.8 mmol/L) and a
      hemoglobin A1C level of 18.0%. The urine examination was negative for ketones.
      Shortly after admission, the patient's blood sugar was controlled with insulin;
      this led to a steady correction of glycemia in the subsequent days. At admission,
      the patient underwent unenhanced brain computed tomography (CT) (Fig 1). Magnetic
      resonance (MR) imaging of the brain was performed 2 days later (Fig 2). After she
      was discharged from the hospital, the involuntary movements progressively
      decreased over the next few weeks until they disappeared. Two months later,
      follow-up unenhanced brain CT (not shown) showed the absence of abnormal
      findings.

PMID- 24661292
TI  - State of the art: Response assessment in lung cancer in the era of genomic
      medicine.
AB  - Tumor response assessment has been a foundation for advances in cancer therapy.
      Recent discoveries of effective targeted therapy for specific genomic
      abnormalities in lung cancer and their clinical application have brought
      revolutionary advances in lung cancer therapy and transformed the oncologist's
      approach to patients with lung cancer. Because imaging is a major method of
      response assessment in lung cancer both in clinical trials and practice,
      radiologists must understand the genomic alterations in lung cancer and the
      rapidly evolving therapeutic approaches to effectively communicate with oncology
      colleagues and maintain the key role in lung cancer care. This article describes
      the origin and importance of tumor response assessment, presents the recent
      genomic discoveries in lung cancer and therapies directed against these genomic
      changes, and describes how these discoveries affect the radiology community. The
      authors then summarize the conventional Response Evaluation Criteria in Solid
      Tumors and World Health Organization guidelines, which continue to be the major
      determinants of trial endpoints, and describe their limitations particularly in
      an era of genomic-based therapy. More advanced imaging techniques for lung cancer
      response assessment are presented, including computed tomography tumor volume and
      perfusion, dynamic contrast material-enhanced and diffusion-weighted magnetic
      resonance imaging, and positron emission tomography with fluorine 18
      fluorodeoxyglucose and novel tracers. State-of-art knowledge of lung cancer
      biology, treatment, and imaging will help the radiology community to remain
      effective contributors to the personalized care of lung cancer patients.

PMID- 24661297
TI  - Scanning protocol for CT angiography in the diagnosis of cardiac allograft
      vasculopathy in heart transplant recipients.

PMID- 24661298
TI  - Features of resolving and nonresolving indeterminate pulmonary nodules at follow
      up CT.

PMID- 24661299
TI  - In memoriam. Maurice M. Reeder, MD.

PMID- 24661300
TI  - In memoriam. Sidney Wallace, MD.

PMID- 24661302
TI  - Editorial comment to role of male pelvic floor muscles and anterior fibromuscular
      stroma in males on alpha1 -blocker treatment: a magnetic resonance imaging study.

PMID- 24661303
TI  - Polyoxometalate-based cobalt-phosphate molecular catalysts for visible light
      driven water oxidation.
AB  - A series of all-inorganic, abundant-metal-based, high-nuclearity cobalt-phosphate
      (Co-Pi) molecular catalysts [{Co4(OH)3(PO4)}4(SiW9O34)4](32-) (1),
      [{Co4(OH)3(PO4)}4(GeW9O34)4](32-) (2), [{Co4(OH)3(PO4)}4(PW9O34)4](28-) (3), and
      [{Co4(OH)3(PO4)}4(AsW9O34)4](28-) (4) were synthesized and shown to be highly
      effective at photocatalytic water oxidation. The {Co16(PO4)4} cluster contains a
      Co4O4 cubane which is structurally analogous to the [Mn3CaO4] core of the oxygen
      evolving complex (OEC) in photosystem II (PSII). Compounds 1-4 were shown to be
      the first POM-based Co-Pi-cluster molecular catalysts for visible light-driven
      water oxidation, thus serving as a functional model of the OEC in PSII. The
      systematic synthesis of four isostructural analogues allowed for investigating
      the influence of different heteroatoms in the POM ligands on the photocatalytic
      activities of these Co-Pi cluster WOCs. Further, the POM-based photocatalysts
      readily recrystallized from the photocatalytic reaction systems with the
      polyoxoanion structures unchanged, which together with the laser flash
      photolysis, dynamic light-scattering, (31)P NMR, UV-vis absorption, POM
      extraction, and ICP-MS analysis results collectively confirmed that compounds 1-4
      maintain their structural integrity under the photocatalytic conditions. This
      study provides not only a valuable molecular model of the "Co-Pi" catalysts with
      a well-defined structure but also an unprecedented opportunity to fine-tune high
      nuclearity POM clusters for visible light-driven water splitting. 

PMID- 24661304
TI  - Editorial comment to Complete response to interferon-alpha in a patient with
      metastatic renal cell carcinoma after unsuccessful molecular-targeted therapies.

PMID- 24661305
TI  - Incidence and precipitants of hospitalization for pancreatitis in people with
      diabetes: the Fremantle Diabetes Study.
AB  - AIMS: To determine the relative risk of pancreatitis in diabetes, and to
      establish whether diabetes-related as well as recognized risk factors contribute.
      METHODS: We studied 1426 participants [mean (SD) age 62.1 (13.3) years, 49.6%
      male, 90.9% type 2 diabetes, median (interquartile range) diabetes duration 4.0
      (1.0-10.0) years] from the community-based Fremantle Diabetes Study Phase I and
      5663 matched residents without diabetes from the same geographical area.
      Pancreatitis hospitalizations between 1982 and 2010 were ascertained using
      validated data linkage. For Fremantle Diabetes Study Phase I participants, chart
      review provided data on the likely causes of pancreatitis. RESULTS: A total of 21
      Fremantle Diabetes Study Phase I participants (1.5%) were hospitalized for
      pancreatitis before study entry vs 29 (0.5%) of contemporaneous residents without
      diabetes. During a mean (SD) of 12.1 (5.4) years of follow-up from entry, 22
      (1.6%) Fremantle Diabetes Study Phase I participants were hospitalized for a
      first-ever episode of pancreatitis on 37 occasions (1.31/1000 person-years)
      compared with 58 (1.0%) residents without diabetes on 81 occasions during a mean
      (SD) 13.6 (4.8) years (0.75/1000 person-years). The age- and sex-adjusted hazard
      ratio (95% CI) for first-ever pancreatitis hospitalization in Fremantle Diabetes
      Study Phase I participants was 1.73 (1.06-2.83; P=0.029). Chart review of 17 of
      the 22 Fremantle Diabetes Study Phase I participants (77%) with incident
      pancreatitis and available case notes revealed that four (24%) presented without
      objective evidence of pancreatitis, seven (41%) presented with cholelithiasis,
      three (18%) with excessive alcohol consumption, two (12%) as a complication of
      elective endoscopic retrograde cholangiopancreatography, and one (6%) with
      hypertriglyceridaemia. CONCLUSION: Consistent with previously published data, the
      risk of pancreatitis was higher in community-dwelling Fremantle Diabetes Study
      Phase I participants but conventional precipitants accounted for confirmed cases.
      These data question whether diabetes-specific risk factors cause or contribute to
      pancreatitis.

PMID- 24661306
TI  - Enhanced recovery following liver surgery: a systematic review and meta-analysis.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) programmes aim to improve
      postoperative outcomes. They are being utilized increasingly in hepatic surgery.
      This review aims to evaluate the impact of ERAS programmes on outcomes following
      liver surgery. METHODS: EMBASE, MEDLINE, PubMed and the Cochrane Database were
      searched for trials comparing outcomes in patients undergoing liver surgery
      utilizing ERAS principles with those in patients receiving conventional care. The
      primary outcome was occurrence of postoperative complications within 30 days.
      Secondary outcomes included length of stay (LoS), functional recovery and
      adherence to ERAS protocols. RESULTS: Nine articles were included in the review,
      of which two were randomized controlled trials (RCTs). Overall complication rates
      were 25.0% (range: 11.5-46.4%) in ERAS patients, and 31.0% (range: 11.8-46.2%) in
      conventional care patients. Significantly reduced overall complication rates
      following ERAS care were demonstrated by a meta-analysis of the data reported in
      the two RCTs (odds ratio: 0.49, 95% confidence interval 0.28-0.84; P = 0.01) The
      median LoS reported by the studies was 5.0 days (range: 2.5-7.0 days) in ERAS
      patients, and 7.5 days (range: 3.0-11.0 days) in non-ERAS patients. Recovery
      milestones, when reported, were improved following ERAS care. CONCLUSIONS: The
      adoption of ERAS protocols improves morbidity and LoS following liver surgery.
      Future ERAS programmes should accommodate the unique requirements of liver
      surgery in order to optimize postoperative outcomes.

PMID- 24661307
TI  - The biogeography of globally threatened seabirds and island conservation
      opportunities.
AB  - Seabirds are the most threatened group of marine animals; 29% of species are at
      some risk of extinction. Significant threats to seabirds occur on islands where
      they breed, but in many cases, effective island conservation can mitigate these
      threats. To guide island-based seabird conservation actions, we identified all
      islands with extant or extirpated populations of the 98 globally threatened
      seabird species, as recognized on the International Union for Conservation of
      Nature Red List, and quantified the presence of threatening invasive species,
      protected areas, and human populations. We matched these results with island
      attributes to highlight feasible island conservation opportunities. We identified
      1362 threatened breeding seabird populations on 968 islands. On 803 (83%) of
      these islands, we identified threatening invasive species (20%), incomplete
      protected area coverage (23%), or both (40%). Most islands with threatened
      seabirds are amenable to island-wide conservation action because they are small
      (57% were <1 km(2) ), uninhabited (74%), and occur in high- or middle-income
      countries (96%). Collectively these attributes make islands with threatened
      seabirds a rare opportunity for effective conservation at scale.

PMID- 24661308
TI  - Quantification of transthyretin kinetic stability in human plasma using subunit
      exchange.
AB  - The transthyretin (TTR) amyloidoses are a group of degenerative diseases caused
      by TTR aggregation, requiring rate-limiting tetramer dissociation. Kinetic
      stabilization of TTR, by preferential binding of a drug to the native tetramer
      over the dissociative transition state, dramatically slows the progression of
      familial amyloid polyneuropathy. An established method for quantifying the
      kinetic stability of recombinant TTR tetramers in buffer is subunit exchange, in
      which tagged TTR homotetramers are added to untagged homotetramers at equal
      concentrations to measure the rate at which the subunits exchange. Herein, we
      report a subunit exchange method for quantifying the kinetic stability of
      endogenous TTR in human plasma. The subunit exchange reaction is initiated by the
      addition of a substoichiometric quantity of FLAG-tagged TTR homotetramers to
      endogenous TTR in plasma. Aliquots of the subunit exchange reaction, taken as a
      function of time, are then added to an excess of a fluorogenic small molecule,
      which immediately arrests further subunit exchange. After binding, the small
      molecule reacts with the TTR tetramers, rendering them fluorescent and detectable
      in human plasma after subsequent ion exchange chromatography. The ability to
      report on the extent of TTR kinetic stabilization resulting from treatment with
      oral tafamidis is important, especially for selection of the appropriate dose for
      patients carrying rare mutations. This method could also serve as a surrogate
      biomarker for the prediction of the clinical outcome. Subunit exchange was used
      to quantify the stabilization of WT TTR from senile systemic amyloidosis patients
      currently being treated with tafamidis (20 mg orally, once daily). TTR kinetic
      stability correlated with the tafamidis plasma concentration. 

PMID- 24661309
TI  - Melanin: the biophysiology of oral melanocytes and physiological oral
      pigmentation.
AB  - The presence of melanocytes in the oral epithelium is a well-established fact,
      but their physiological functions are not well defined. Melanin provides
      protection from environmental stressors such as ultraviolet radiation and
      reactive oxygen species; and melanocytes function as stress-sensors having the
      capacity both to react to and to produce a variety of microenvironmental
      cytokines and growth factors, modulating immune, inflammatory and antibacterial
      responses. Melanocytes also act as neuroendocrine cells producing local
      neurotransmitters including acetylcholine, catecholamines and opioids, and
      hormones of the melanocortin system such as proopiomelanocortin,
      adrenocorticotropic hormone and alpha-melanocyte stimulating hormone, that
      participate in intracellular and in intercellular signalling pathways, thus
      contributing to tissue homeostasis.There is a wide range of normal variation in
      melanin pigmentation of the oral mucosa. In general, darker skinned persons more
      frequently have oral melanin pigmentation than light-skinned persons. Variations
      in oral physiological pigmentation are genetically determined unless associated
      with some underlying disease.In this article, we discuss some aspects of the
      biophysiology of oral melanocytes, of the functions of melanin, and of
      physiological oral pigmentation. 

PMID- 24661310
TI  - Unravelling the multifaceted roles of Atg proteins to improve cancer therapy.
AB  - Autophagy follows a lysosomal degradation pathway in which a cell digests its own
      components. It is highly regulated by a limited number of autophagy-related genes
      (Atg) and the proteins they encode, that are crucial for cells to undergo the
      process via modulating autophagsome formation. Recently, accumulating evidence
      has revealed the core molecular machinery of autophagy; however, intricate
      relationships between autophagy and cancer remain an enigma. Several studies have
      shown that Atgs can play an important role in carcinogenesis, by which Atgs may
      modulate a series of oncogenic and tumour suppressive pathways, implicating
      microRNA (miRNA) involvement. In this review, we will present the key role of
      Atgs in deciding the fate of cancer cells, discuss some representative Atgs and
      their proteins such as ULK, Beclin-1, and Atg8/LC3-Atg4, which can also be
      regulated by miRNAs. Thus, Atgs can be considered to be targets for cancer
      treatment, which may illuminate the future of cancer therapy. 

PMID- 24661311
TI  - Rickettsiaceae and Anaplasmataceae infections in Ixodes ricinus ticks from urban
      and natural forested areas of Poland.
AB  - BACKGROUND: Ixodes ricinus is a major vector for a range of microbial pathogens
      and the most prevalent and widely distributed tick species on the European
      continent, occurring in both natural and urban habitats. Nevertheless, little is
      known about the relative density of ticks in these two ecologically distinct
      habitats and the diversity of tick-borne pathogens that they carry. METHODS: We
      compared densities of questing I. ricinus nymphs and adults in urban and natural
      habitats in Central and Northeastern Poland, assessed the prevalence and rate of
      co-infection with A. phagocytophilum, Rickettsia, Ehrlichia and 'Ca. Neoehrlichia
      spp.' in ticks, and compared the diversity of tick-borne pathogens using
      molecular assays (PCR). RESULTS: Of the 1325 adults and nymphs, 6.2% were
      infected with at least one pathogen, with 4.4%, 1.7% and less than 0.5% being
      positive for the DNA of Rickettsia spp., A. phagocytophilum, Ehrlichia spp. and
      Ca. N. mikurensis, respectively. Although tick abundance was higher in natural
      habitats, the prevalence of the majority of pathogens was higher in urban
      forested areas. CONCLUSION: We conclude that: (i) zoonotic genetic variants of A.
      phagocytophilum are widely distributed in the Polish tick population, (ii)
      although the diversity of tick borne pathogens was higher in natural habitats,
      zoonotic species/strains were detected only in urban forests, (iii) and we
      provide the first description of Ca. N. mikurensis infections in ticks in Poland.

PMID- 24661312
TI  - Randomized controlled trial to assess the short-term effectiveness of tailored
      web- and text-based facilitation of smoking cessation in primary care (iQuit in
      practice).
AB  - AIMS: To estimate the short-term effectiveness, feasibility and acceptability of
      a smoking cessation intervention (the iQuit system) that consists of tailored
      printed and Short Message Service (SMS) text message self-help delivered as an
      adjunct to cessation support in primary care to inform the design of a definitive
      trial. DESIGN: A stratified two parallel-group randomized controlled trial
      comparing usual care (control) with usual care plus the iQuit system
      (intervention), delivered by primary care nurses/healthcare assistants who were
      blinded to the allocation sequence. SETTING: Thirty-two general practice (GP)
      surgeries in England, UK. PARTICIPANTS: A total of 602 smokers initiating smoking
      cessation support from their local GP surgery were randomized (control n = 303,
      intervention n = 299). MEASUREMENTS: Primary outcome was self-reported 2-week
      point prevalence abstinence at 8 weeks follow-up. Secondary smoking outcomes and
      feasibility and acceptability measures were collected at 4 weeks after quit date,
      8 weeks and 6 months follow-up. FINDINGS: There were no significant between-group
      differences in the primary outcome [control 40.3%, iQuit 45.2%; odds ratio (OR) =
      1.22, 95% confidence interval (CI) = 0.88-1.69] or in secondary short-term
      smoking outcomes. Six-month prolonged abstinence was significantly higher in the
      iQuit arm (control 8.9%, iQuit 15.1%; OR = 1.81, 95% CI = 1.09-3.01). iQuit
      support took on average 7.7 minutes (standard deviation = 4.0) to deliver and
      18.9% (95% CI = 14.8-23.7%) of intervention participants discontinued the text
      message support during the programme. CONCLUSIONS: Tailored printed and text
      message self-help delivered alongside routine smoking cessation support in
      primary care does not significantly increase short-term abstinence, but may
      increase long-term abstinence and demonstrated feasibility and acceptability
      compared with routine cessation support alone.

PMID- 24661313
TI  - Association of LOX-1 gene polymorphisms with cerebral infarction in northern
      Chinese Han population.
AB  - BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays
      an important role in the pathophysiology of atherosclerosis and thrombosis. This
      study is aimed at evaluating the potential association of 3'-UTR-C188T and G501C
      in LOX-1 gene with cerebral infarction. METHODS: A total of 386 patients with
      cerebral infarction and 386 healthy controls were included in the study, which
      were unrelated Chinese Han population in the Liaoning Province of northern China.
      The single nucleotide polymorphisms, 3'-UTR-C188T and G501C, were analyzed by
      polymerase chain reaction-ligation detection reaction method. RESULTS: The
      frequencies of CC + GC genotype, GC genotype and C allele of G501C in the
      patients with cerebral infarction were significantly higher than those in the
      controls (P < 0.01, P < 0.01, P = 0.04, respectively). The correlation still
      remained after adjusting for confounding risk factors of cerebral infarction. In
      addition, no significant association was observed between 3'-UTR-C188T and
      cerebral infarction. CONCLUSIONS: The study indicated that the G501C variant in
      LOX-1 gene may be associated with susceptibility to cerebral infarction,
      independent of other common risk factors, in northern Chinese Han population.

PMID- 24661314
TI  - Management of acute infectious diarrhea for children living in resource-limited
      settings.
AB  - Acute infectious gastroenteritis continues to be a leading cause of morbidity and
      mortality in children below 5 years of age, with the majority of deaths
      concentrated in 35 'low income' countries. In these countries the under five
      years of age mortality rates reach 100 per 1000 live births, of which a
      significant proportion are associated with acute diarrhea. Rotavirus,
      cryptosporidium, Shigella spp and enterotoxigenic Escherichia coli are the main
      pathogens causing disease in these settings, although other bacteria and
      parasites can cause moderate to severe disease in different regions and
      situations. Treatment of children in these setting should be focused on
      appropriate rehydration, early hospitalization of severely malnourished children,
      zinc supplementation, and in specific situations, antimicrobials should be
      considered. The rationale for antimicrobial use should be based on the potential
      benefits based on published literature and the opportunity for use. This review
      provides a pathogen-specific update on the potential benefits of antimicrobials
      and suggests an empirical management approach for children suffering an acute
      watery or bloody diarrhea in a resource-limited region. 

PMID- 24661316
TI  - Abstracts of the Thoracic Society of Australia & New Zealand and the Australian &
      New Zealand Society of Respiratory Science 2014 Annual Scientific Meetings, 4-9
      April 2014, Adelaide, SA.

PMID- 24661317
TI  - Cutaneous adverse effects of BRAF inhibitors in metastatic malignant melanoma, a
      prospective study in 20 patients.
AB  - BACKGROUND: BRAF inhibitors frequently cause significant cutaneous adverse
      reactions. OBJECTIVE: To study the timing, prevalence and response to treatment
      of skin lesions in patients receiving V-raf murine sarcoma viral oncogene homolog
      B1 (BRAF) inhibitors. METHODS: We prospectively studied the cutaneous side
      effects of patients with a BRAF mutant (V600E, V600K, V600R) metastatic malignant
      melanoma treated with a BRAF inhibitor. We systematically registered prevalence,
      timing of onset and response to treatment. RESULTS: Twenty patients were treated
      for 2-52 weeks with a BRAF inhibitor. Eleven patients on vemurafenib (58%)
      developed cutaneous side-effects and 10 patients (42%) had more than one
      cutaneous adverse event. Verrucous papillomas were observed in eight patients
      (42%), after 1-12 weeks. We diagnosed four keratoacanthomas in two patients (11%)
      after 6-10 weeks and two squamous cell carcinomas in two patients (11%) after 10
      16 weeks. Seven patients (37%) developed a hyperkeratotic, folliculocentric
      eruption after 2-8 weeks, resolving quickly under topical steroids. Four patients
      (21%) presented a facial erythema, two patients (11%) a seborrhoeic dermatitis
      like eczema on the scalp. Three patients (16%) developed cystic lesions after 2
      11 weeks. Three patients (16%) presented a hand-foot skin reaction after 4-6
      weeks, which was successfully treated with topical steroids and keratolytics.
      Hyperkeratosis of the nipples was seen in one patient (5%). We observed
      phototoxic reactions after UV exposure in five patients (26%) and alopecia in two
      patients (11%) after 8-10 weeks. One patient on dabrafenib developed curly hairs
      (24 weeks), keratotic papules (1 and 36 weeks), a keratoacanthoma (4 weeks) and a
      hand-foot skin reaction (31 weeks). CONCLUSION: Multiple cutaneous toxicities
      were observed in patients under BRAF inhibitors, mostly well controlled with
      adequate treatment. We recommend a multidisciplinary approach with regular
      assessments of the skin by a dermatologist. This allows early identification and
      adequate treatment to avoid premature discontinuation of a life-prolonging
      therapy.

PMID- 24661318
TI  - Bacteremic skin and soft tissue infection caused by Prevotella loescheii.
AB  - BACKGROUND: Anaerobes are a major component of gut flora. They play an important
      role in the pathogenesis of infections resulting from breaches in mucus
      membranes. Because of the difficulties in cultivating and identifying it, their
      role continues to be undermined. The purpose of this paper is to report a case of
      Prevotella loescheii bacteremic skin and soft tissue infection and review the
      literature. CASE PRESENTATION: A 42-year-old Caucasian man was admitted for an
      elective bariatric surgery. A lengthy intensive care unit stay and buttocks
      decubitus ulcers complicated his post-operative course. After being transferred
      to a long-term care facility, the decubitus ulcer became secondarily infected
      with multiple bacteria including P. loescheii; an anaerobe that grew in blood and
      wound cultures. The patient was treated successfully with aggressive surgical
      debridement, antibiotics and subsequent wound care. CONCLUSION: P. loescheii
      colonizes the gut and plays an important role in periodontal infections. In rare
      occasions and under suitable circumstances, it can infect skin and soft tissues
      as well as joints. Given the difficulties in isolating anaerobes in the
      microbiology lab, considering this bacterium alongside other anaerobes in
      infections of devitalized tissue is indicated even if cultures were reported
      negative.

PMID- 24661319
TI  - Acute pain services and postsurgical pain management in the Netherlands: a
      survey.
AB  - BACKGROUND: Acute postoperative pain is still inadequately managed, despite the
      presence of acute pain services (APSs). This study aimed to investigate the
      existence, structure, and responsibilities of Dutch APSs and to review the
      implementation of the Dutch Hospital Patient Safety Program (DHPSP). METHODS:
      Information was gathered by a digital questionnaire, sent to all 96 Dutch
      hospitals performing surgical procedures. RESULTS: Completed questionnaires were
      received from 80 hospitals (83%), of which 90% have an APS. Important duties of
      the APS are regular patient rounds, checking complex pain techniques (100%),
      supporting quality improvement of pain management (87%), pain education (100%),
      and pain research (21%). IMPLEMENTATION OF THE DHPSP: Regular in-hospital pain
      training is not provided in 46% of the hospitals. Thirteen percent of the
      hospitals offer no patient information about pain management. CONCLUSIONS: Almost
      all hospitals have an APS. They differ in both the way they are locally
      organized, along with the activities they employ. Future research needs to
      compare the effect of patient and nonpatient-related activities of APSs on
      outcomes related to pain management.

PMID- 24661320
TI  - Allergenicity of potato proteins and of their conjugates with galactose,
      galactooligosaccharides, and galactan in native, heated, and digested forms.
AB  - The effect of glycation of potato proteins on their immunoreactivity was studied
      by using a pool of human sera with specific IgE to potato proteins. Patatin
      conjugates were more immunoreactive than protease inhibitors ones. To better
      understand this behavior, the changes in patatin structure upon glycation and
      heat treatment were investigated. Patatin demonstrated an increase in total
      immunoreactivity when glycated with galactose and galactooligosaccharides.
      However, galactan conjugation to patatin resulted in a decrease in
      immunoreactivity by restricting IgE's access to the epitopes. Although the heat
      treatment resulted in a decrease in patatin's immunoreactivity through
      aggregation, it was less effective when patatin conjugates were used due to the
      decrease in aggregation and the secondary structural changes. Upon digestion,
      native patatin exhibited the largest decrease in immunoreactivity resulting from
      the disruption of both conformational and sequential epitopes. Patatin conjugates
      were less digested and had higher IgE-immunoreactivity as compared to the
      digested patatin. 

PMID- 24661321
TI  - Comparative analysis of anthocyanin biosynthesis during fruit development in two
      Lycium species.
AB  - Dietary consumption of functional foods enriched in anthocyanins benefit for
      human health by protection against far-ranging human diseases. Delphinidin
      derived anthocyanins (valuable as blue pigments and antioxidants) are accumulated
      specifically in the fruits of Lycium ruthenicum but not in the fruits of Lycium
      barbarum, suggesting the differences of anthocyanin biosynthesis between the two
      species. In this study, anthocyanin profiling confirmed that anthocyanins were
      increasingly accumulated during fruit ripening in L. ruthenicum, and sharply
      increased at full expanded mature fruit, while no anthocyanin were detected at
      any stage of L. barbarum fruit development. Several genes involved in anthocyanin
      biosynthesis were characterized in L. ruthenicum and L. barbarum fruits.
      Expression profiling of these genes during fruit development showed a significant
      positive correlation between transcript abundance and anthocyanin accumulation in
      L. ruthenicum fruit. Meanwhile, transcripts in L. barbarum fruit were either
      undetectable or were downregulated during fruit ripening, before increasing
      slightly in the final stages of maturation. In addition, the ratio of
      LrF3'5H/LrF3'H transcription showed a gradual increase before 6 days after
      breaker (DAB) and a sharp enhancement at 10 DAB. Our results suggest that the
      expression patterns of both regulatory and structural genes and the
      transcriptional ratio of branch-node structural genes F3'5'H/F3'H may determine
      the phenotypic difference in anthocyanin biosynthesis between L. ruthenicum and
      L. barbarum fruits.

PMID- 24661322
TI  - Patients' preferences for post-treatment breast cancer follow-up in primary care
      vs. secondary care: a qualitative study.
AB  - OBJECTIVE: To explore patients' preferences for follow-up in primary care vs.
      secondary care. METHODS: A cross-sectional design was employed, involving semi
      structured interviews with 70 female patients with a history of early-stage
      breast cancer. Using descriptive content analysis, interview transcripts were
      analysed independently and thematically by two researchers. FINDINGS: Patients
      expressed the strongest preference for annual visits (31/68), a schedule with a
      decreasing frequency over time (27/68), and follow-up > 10 years, including
      lifelong follow-up (20/64). The majority (56/61) preferred to receive follow-up
      care from the same care provider over time, for reasons related to a personal
      doctor-patient relationship and the physician's knowledge of the patient's
      history. About 75% (43/56) preferred specialist follow-up to other follow-up
      models. However, primary care-based follow-up would be accepted by 57% (39/68)
      provided that there is good communication between GPs and specialists, and
      sufficient knowledge among GPs about follow-up. Perceived benefits of primary
      care-based follow-up referred to the personal nature of the GP-patient
      relationship and the easy access to primary care. Perceived barriers included
      limited oncology knowledge and skills, time available, motivation among GPs to
      provide follow-up care and patients' confidence with the present specialist
      follow-up. CONCLUSIONS: More than half of the patients were open to primary care
      based follow-up. Patients' confidence with this follow-up model may increase by
      using survivorship care plans to facilitate communication across the
      primary/secondary interface and with patients. Training GPs to improve their
      oncology knowledge and skills might also increase patients' confidence.

PMID- 24661323
TI  - IMRT with 18FDG-PET?CT based simultaneous integrated boost for treatment of nodal
      positive cervical cancer.
AB  - BACKGROUND: To evaluate toxicity and outcome of intensity modulated radiotherapy
      (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in
      patients with loco-regional advanced cervical cancer (LRACC). METHODS: The study
      population comprised ten patients with 18FDG-PET?CT positive lymph nodes (LNs),
      who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily
      fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary
      tumor received an additional external beam boost to a total dose of 55.8 Gy. A
      SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET?CT
      positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 - 18 Gy)
      was administered to the primary tumor. The primary goal of this study was to
      evaluate acute and early late toxicity and loco-regional control. RESULTS: The
      median number of irradiated LNs per patient was 3 (range: 1-6) with a median
      middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up
      was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was
      observed in 1 patient. Three of the patients developed a recurrence, one in the
      form of a local tumor relapse, one had a paraaortic LN metastasis outside the
      treated volume and the last one developed a distant metastasis. CONCLUSION: IMRT
      with SIB in the region of 18FDG-PET positive lymph nodes appears to be an
      effective therapy with acceptable toxicity and might be useful in the treatment
      of patients with locally advanced cervical cancer.

PMID- 24661324
TI  - Clinical and biological moderators of response to naltrexone in alcohol
      dependence: a systematic review of the evidence.
AB  - AIM: The goal of this systematic review was to identify moderators of naltrexone
      efficacy in the treatment of alcohol dependence. METHODS: We searched Pubmed,
      CINHAL, Embase, PsycINFO and the Cochrane Library from 1990 to April 2012 and
      reference lists of pertinent review articles, which yielded 622 trial, pooled
      analysis and review articles. Using pre-established eligibility criteria, two
      reviewers independently determined whether abstracts contained evidence of
      demographic or biological characteristics, i.e. moderators, influencing
      naltrexone response in alcohol dependence. We assessed each publication for risk
      of bias and evaluated the strength of the body of evidence for each moderator.
      RESULTS: Twenty-eight publications (on 20 studies) met criteria for data
      synthesis. These included 26 publications from 12 randomized, placebo-controlled
      trials, three non-randomized, non-placebo studies and one randomized, non-placebo
      study. In addition, there were two publications from pooled analyses of four
      randomized, placebo-controlled trials. Family history of alcohol problems and the
      Asn40Asp polymorphism of the MU-opioid receptor gene showed a positive
      association with efficacy in four of five and three of five studies,
      respectively. Other moderators reported to be associated with efficacy included
      male sex (two of five studies), pre-treatment drinking (two of two studies) and
      high craving (two of five studies). However, the overall risk of bias in the
      published literature is high. CONCLUSIONS: The identification of naltrexone
      responsive alcohol-dependent patients is still in development. Studies to date
      point to two potential moderators-family history and presence of the OPRM1
      Asn40Asp polymorphism-as having the strongest evidence. However, the data to date
      is still insufficient to recommend that any moderator be used in determining
      clinical treatment.

PMID- 24661325
TI  - Feature combination networks for the interpretation of statistical machine
      learning models: application to Ames mutagenicity.
AB  - BACKGROUND: A new algorithm has been developed to enable the interpretation of
      black box models. The developed algorithm is agnostic to learning algorithm and
      open to all structural based descriptors such as fragments, keys and hashed
      fingerprints. The algorithm has provided meaningful interpretation of Ames
      mutagenicity predictions from both random forest and support vector machine
      models built on a variety of structural fingerprints.A fragmentation algorithm is
      utilised to investigate the model's behaviour on specific substructures present
      in the query. An output is formulated summarising causes of activation and
      deactivation. The algorithm is able to identify multiple causes of activation or
      deactivation in addition to identifying localised deactivations where the
      prediction for the query is active overall. No loss in performance is seen as
      there is no change in the prediction; the interpretation is produced directly on
      the model's behaviour for the specific query. RESULTS: Models have been built
      using multiple learning algorithms including support vector machine and random
      forest. The models were built on public Ames mutagenicity data and a variety of
      fingerprint descriptors were used. These models produced a good performance in
      both internal and external validation with accuracies around 82%. The models were
      used to evaluate the interpretation algorithm. Interpretation was revealed that
      links closely with understood mechanisms for Ames mutagenicity. CONCLUSION: This
      methodology allows for a greater utilisation of the predictions made by black box
      models and can expedite further study based on the output for a (quantitative)
      structure activity model. Additionally the algorithm could be utilised for
      chemical dataset investigation and knowledge extraction/human SAR development.

PMID- 24661326
TI  - Expression of cathepsin K in periodontitis and in gingival fibroblasts.
AB  - OBJECTIVE: To study non-osteoclastic sources of cathepsin K in periodontitis.
      MATERIALS AND METHODS: Tissue samples were obtained from 10 otherwise healthy
      periodontitis pati-ents during routine periodontal flap operations and 10
      systemically and periodontally healthy individuals who underwent extraction
      operations for retained third molars. Methods used were immunohistochemistry,
      image analysis, immunofluorescence double-staining, gingival fibroblast culture,
      tumour necrosis factor-alpha (TNF-alpha) stimulation and Western blotting.
      RESULTS: Macrophage-like cells, fibroblast-like cells, vascular endothelial cells
      and gingival epithelial cells were more intensively stained for cathepsin K and
      also more frequent in periodontitis than in controls (665 +/- 104 vs 258 +/- 40
      cells mm(-2) , P < 0.01). Some cathepsin K(+) cells in periodontal tissues were
      CD68(+) , but some were CD68(-) and probably fibroblasts. Indeed, in gingival
      fibroblast culture, resting fibroblasts released cathepsin K, more 43 kD
      procathepsin K than 29 kD active cathepsin K. TNF-alpha increased the release of
      the activated cathepsin K 4- to 5-fold. CONCLUSIONS: Results suggest that GCF
      cathepsin K is not only osteoclast-derived, but in periodontitis, also other
      cells contribute to it. GCF-cathepsin K, perhaps together with intracellular,
      lysosomal collagenolytically active cathepsin K in fibroblasts, macrophages and
      gingival epithelial cells, can contribute to the loss of attachment and
      destruction of the periodontal ligament.

PMID- 24661327
TI  - Porphyromonas gingivalis gingipain is involved in the detachment and aggregation
      of Aggregatibacter actinomycetemcomitans biofilm.
AB  - Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are major
      periodontal pathogens that cause several types of periodontal disease. Our
      previous study suggested that P. gingivalis gingipains secreted in the
      subgingival environment are related to the detachment of A.actinomycetemcomitans
      biofilms. However, it remains unclear whether arginine-specific cysteine
      proteinase (Rgp) and lysine-specific proteinase (Kgp) play different roles in the
      detachment of A. actinomycetemcomitans biofilm. The aim of this study was to
      investigate possible disruptive roles of Kgp and Rgp in the aggregation and
      attachment of A. actinomycetemcomitans. While P. gingivalis ATCC33277 culture
      supernatant has an ability to decrease autoaggregation and coaggregation of A.
      actinomycetemcomitans cells, neither the boiled culture supernatant of ATCC33277
      nor the culture supernatant of KDP136 showed this ability. The addition of KYT-1
      and KYT-36, specific inhibitors of Rgp and Kgp, respectively, showed no influence
      on the ability of P. gingivalis culture supernatant. The result of gelatin
      zymography suggested that other proteases processed by gingipains mediated the
      decrease of A. actinomycetemcomitans aggregations. We also examined the biofilm
      destructive effect of gingipains by assessing the detachment of A.
      actinomycetemcomitans from polystyrene surfaces. Scanning electron microscope
      analysis indicated that A. actinomycetemcomitans cells were detached by P.
      gingivalis Kgp. The quantity of A. actinomycetemcomitans in biofilm was decreased
      in co-culture with P. gingivalis. However, this was not found after the addition
      of KYT-36. These findings suggest that Kgp is a critical component for the
      detachment and decrease of A. actinomycetemcomitans biofilms. 

PMID- 24661328
TI  - Thymosin beta4 coated nanofiber scaffolds for the repair of damaged cardiac
      tissue.
AB  - After a cardiac event, proper treatment and care of the damaged tissue is crucial
      in restoring optimal cardiac function and preventing future cardiac events.
      Recently, thymosin beta4 has been found to play a vital role in cardiac cell
      health and development by regulating angiogenesis, inflammatory responses, and
      wound healing. We proposed that defined poly(epsilon-caprolactone) (PCL)
      nanoscaffolds coated with thymosin beta4 could efficiently differentiate murine
      derived cardiomyocytes into functioning cardiac tissue. PCL nanoscaffolds were
      developed through electrospinning technology, and subsequently coated with a
      thymosin beta4 solution. Cardiomyocytes were seeded on coated and uncoated
      nanoscaffolds and observed for six days via fluorescent and electron microscopy.
      Our results demonstrated a robust growth and differentiation of cardiomyocytes on
      coated nanoscaffolds compared with uncoated, showing potential for nanoscaffold
      mediated cardiac cell replacement in vivo after an MI or other cardiac event. 

PMID- 24661329
TI  - Adenine auxotrophy--be aware: some effects of adenine auxotrophy in Saccharomyces
      cerevisiae strain W303-1A.
AB  - Adenine auxotrophy is a commonly used genetic marker in haploid yeast strains.
      Strain W303-1A, which carries the ade2-1 mutation, is widely used in
      physiological and genetic research. Yeast extract-based rich medium contains a
      low level of adenine, so that adenine is often depleted before glucose. This
      could affect the cell physiology of adenine auxotrophs grown in rich medium. The
      aim of our study was to assess the effects of adenine auxotrophy on cell
      morphology and stress physiology. Our results show that adenine depletion halts
      cell division, but that culture optical density continues to increase due to cell
      swelling. Accumulation of trehalose and a coincident 10-fold increase in
      desiccation stress tolerance is observed in adenine auxotrophs after adenine
      depletion, when compared to prototrophs. Under adenine starvation, long-term
      survival of W303-1A is lower than during carbon starvation, but higher than
      during leucine starvation. We observed drastic adenine-dependent changes in cell
      stress physiology, suggesting that results may be biased when adenine auxotrophs
      are grown in rich media without adenine supplementation. 

PMID- 24661330
TI  - Editorial comment.

PMID- 24661331
TI  - Advances in renal neoplasia: recommendations from the 2012 International Society
      of Urological Pathology Consensus Conference.
AB  - The International Society of Urological Pathology (ISUP) 2012 Consensus
      Conference made recommendations regarding the classification, prognostic factors,
      staging, and immunohistochemical and molecular assessment of adult renal tumors.
      There was consensus that 5 entities should be recognized as novel tumors:
      tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC,
      clear cell papillary RCC, microphthalmia transcription factor-family
      translocation RCC [in particular t(6; 11) RCC], and hereditary leiomyomatosis RCC
      syndrome-associated RCC. In addition, 3 rare epithelial carcinomas were
      considered emerging or provisional entities: thyroid-like follicular RCC,
      succinate dehydrogenase B deficiency-associated RCC, and anaplastic lymphoma
      kinase translocation RCC. There were also a number of suggested modifications to
      existing World Health Organization 2004 categories, with the new classification
      to be known as the ISUP Vancouver Classification. Tumor morphotype,
      sarcomatoid/rhabdoid differentiation, and tumor necrosis were identified as
      significant prognostic parameters for RCC. The ISUP Grading System was accepted
      with grades 1-3 of clear cell and papillary RCC being based on nucleolar
      prominence, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid
      differentiation defined grade 4 tumors. It was agreed that chromophobe RCC should
      not be graded. Consensus guidelines were formulated for specimen handling, and it
      was agreed that renal sinus invasion is present when tumor is in direct contact
      with fat or loose connective tissue of the sinus or if there is involvement of
      endothelial-lined spaces within the renal sinus, regardless of the size. The role
      of biomarkers in the diagnosis and assessment of prognosis of renal tumors was
      considered, and panels of immunohistochemical markers were identified for use in
      specific differential diagnostic scenarios. 

PMID- 24661332
TI  - Drug and device development for localized prostate cancer: report of a Food and
      Drug Administration/American Urological Association public workshop.
AB  - Summary of the discussion at a public workshop cosponsored by the U.S. Food and
      Drug Administration (FDA) and the American Urological Association reviewing
      potential trial designs for product and device development for the treatment of
      localized prostate cancer. Product development for treatment of localized
      prostate cancer has been stymied by the impracticality of using overall survival
      as an endpoint in patients with localized disease and the lack of acceptable
      surrogate endpoints. A workshop evaluating potential trial designs for the
      development of therapies for localized prostate cancer was held in San Diego, CA,
      in May 2013. Invited experts represented multiple stakeholders, including
      urology, medical oncology, radiation oncology, industry, and patient advocates.
      The expert panel discussed development of products for all risk strata of
      clinically localized prostate cancer. The panel responded to specific questions
      from FDA, discussing trial design for patients with low-, intermediate-, and high
      risk prostate cancer, focal therapy for prostate cancer, patients who have
      undergone definitive radiation therapy, and adjuvant therapy for patients
      undergoing radiation therapy or surgery. Expert commentary provided by the panel
      will inform a planned FDA guidance on pathways for product and device development
      for treatment of localized prostate cancer and will be discussed at meetings of
      the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of
      principles that can be used to promote the development of new products or devices
      for the treatment of this disease. 

PMID- 24661333
TI  - Long-term tolerability and efficacy of degarelix: 5-year results from a phase III
      extension trial with a 1-arm crossover from leuprolide to degarelix.
AB  - OBJECTIVE: To demonstrate the safety and efficacy of up to 5 years of degarelix
      treatment and the effects of crossing over from leuprolide to degarelix in the
      extension phase of a phase III pivotal 1-year trial. METHODS: Patients receiving
      degarelix who completed the 1-year trial continued on 80 mg (n = 125) or 160 mg
      (n = 126) maintenance doses. Patients who received leuprolide were rerandomized
      to degarelix 240/80 mg (n = 69) or 240/160 mg (n = 65). Safety and tolerability
      were assessed (primary end point), as well as testosterone and prostate-specific
      antigen levels and prostate-specific antigen progression-free survival (secondary
      end points). RESULTS: Adverse event frequency was similar between both the
      groups. Adverse events included initial injection site reactions, hot flushes,
      and increased weight. Testosterone and prostate-specific antigen values during
      the extension study were similar to those seen during the 1-year trial in
      patients who continued on degarelix or crossed over from leuprolide. The prostate
      specific antigen progression-free survival hazard rate was decreased
      significantly after the crossover in the leuprolide to degarelix group (from 0.20
      to 0.09; P = .002), whereas in patients who continued on degarelix, the rate did
      not change significantly. In patients with baseline prostate-specific antigen >20
      ng/mL, the same hazard rate change pattern was observed on crossover (from 0.38
      to 0.19; P = .019). CONCLUSION: Degarelix was well tolerated; no safety concerns
      were identified. The significant prostate-specific antigen progression-free
      survival benefit established for degarelix over leuprolide during year 1 remained
      consistent at 5 years.

PMID- 24661335
TI  - Increased incidence of invasive bacterial disease in chronic obstructive
      pulmonary disease compared to the general population--a population based cohort
      study.
AB  - BACKGROUND: Innate defence mechanisms of the airways are impaired in chronic
      obstructive pulmonary disease (COPD), predisposing patients to lower respiratory
      tract infections, but less is known about the association with other infections.
      In this population-based cohort study, we investigated the associations between
      COPD and invasive bacterial disease by comparing incidence rates of bacteraemia
      in COPD patients and randomly selected reference individuals from the general
      population. METHODS: In this population based cohort study all patients with
      COPD, >=40 years of age, who were discharged from hospitals in southern Sweden
      between 1990 and 2003 were identified in the Swedish Inpatient Register (n =
      15,403). Age and gender matched reference individuals were randomly selected from
      the general population. Records were cross-referenced to the microbiological
      databases covering the region, 1990-2010. The hazard ratios (HR) of bloodstream
      infections and hospitalisations for infections were estimated by Cox proportional
      hazards regression. RESULTS: We found that individuals with COPD had a 2.5-fold
      increased incidence of bacteraemia compared to the reference individuals from the
      general population adjusted for other co-morbidity and socio-economic status
      (hazard ratio: 2.5, 95% confidence interval: 2.2-2.7). The increased incidence of
      bacteraemia was paralleled by an increased incidence of hospitalisation for non
      respiratory infections, i.e., skin infections, pyelonephritis, or septic
      arthritis. Despite higher absolute rates of bloodstream infections among COPD
      patients than among the general population, the distribution of different
      pathogens was similar. CONCLUSIONS: In summary this population-based study shows
      COPD is associated with an increased incidence of invasive bacterial infections
      compared to the general population, indicating a general frailty of acquiring
      severe infections in addition to the specific susceptibility to infections of
      respiratory origin. The underlying contributory factors (e.g. smoking,
      corticosteroid use, co-morbid diseases or a frailty inherent to COPD itself) need
      to be disentangled in further studies.

PMID- 24661336
TI  - Dermatosis in children with oedematous malnutrition (Kwashiorkor): a review of
      the literature.
AB  - Children with oedematous malnutrition, known as kwashiorkor, may develop a
      characteristic skin lesion, named 'Dermatosis of Kwashiorkor' (DoK). Only a few
      studies have been concerned with this condition, and the reason for the
      development of DoK remains unexplained. This study review the existing studies
      concerning DoK, including its clinical manifestations, histopathology, suggested
      pathophysiology, current treatment and prognosis for children of the age of 6
      months to 5 years. Standardized clinical studies are needed to further understand
      the implications of DoK. Such studies would suffer from the lack of consistency
      concerning the terminology and scoring of the lesions in DoK. We therefore stress
      the need for a standardized scoring of the degree of DoK. This would facilitate
      valid and comparable studies and the development of better treatment for this
      vulnerable group of patients. 

PMID- 24661334
TI  - Nucleotide excision repair in Trypanosoma brucei: specialization of transcription
      coupled repair due to multigenic transcription.
AB  - Nucleotide excision repair (NER) is a highly conserved genome repair pathway
      acting on helix distorting DNA lesions. NER is divided into two subpathways:
      global genome NER (GG-NER), which is responsible for repair throughout genomes,
      and transcription-coupled NER (TC-NER), which acts on lesions that impede
      transcription. The extent of the Trypanosoma brucei genome that is transcribed is
      highly unusual, since most genes are organized in multigene transcription units,
      each transcribed from a single promoter. Given this transcription organization,
      we have addressed the importance of NER to T. brucei genome maintenance by
      performing RNAi against all predicted contributing factors. Our results indicate
      that TC-NER is the main pathway of NER repair, but only CSB, XPBz and XPG
      contribute. Moreover, we show that UV lesions are inefficiently repaired in T.
      brucei, perhaps due to preferential use of RNA polymerase translesion synthesis.
      RNAi of XPC and DDB was found to be lethal, and we show that these factors act in
      inter-strand cross-link repair. XPD and XPB appear only to act in transcription,
      not repair. This work indicates that the predominance of multigenic transcription
      in T. brucei has resulted in pronounced adaptation of NER relative to the host
      and may be an attractive drug target. 

PMID- 24661337
TI  - The health and service needs of older veterans: a qualitative analysis.
AB  - BACKGROUND: With substantial numbers of older people within the Australian
      veteran population continuing to age well within the community, appropriate
      planning of community support and health services is important for this ageing
      population. OBJECTIVE: The purpose of this research study was to investigate the
      health and service usage of a group of older Australian war veterans who receive
      Australian Government support for their health-care needs and conditions. DESIGN:
      This paper reports on qualitative data gathered from the longitudinal MELSHA
      study. Utilizing thematic analysis and the theoretical framework of locus of
      control, this article reports on 25 qualitative interviews of veterans and their
      widows about their DVA-related health and service usage. RESULTS: Participants
      within this study were determined to maintain a sense of control and independence
      in relation to their living circumstances and service usage. In doing so, they
      attempted to maintain their current community living circumstances and
      independence while minimizing their utilization of services and perceived
      'burden' on family members and friends. Participants accepted that a decline in
      health status was inevitable, but engaged in a number of different strategies to
      maintain their current way of life for as long as possible. DISCUSSION &
      CONCLUSION: Participants, while valuing an internal locus of control, generally
      engaged in an integrative locus of control to maintain a sense of control and
      independence in their daily lives. In addition, participants were very grateful
      of the services provided by the DVA and acknowledged their role in maintaining
      their independence within the community.

PMID- 24661338
TI  - Quantitative assessment of the diagnostic role of APC promoter methylation in non
      small cell lung cancer.
AB  - BACKGROUND: Adenomatous polyposis coli (APC) has been reported to be a candidate
      tumor suppressor in many cancers. However, the diagnostic role of APC promoter
      methylation in non-small cell lung cancer (NSCLC) remains unclear. We
      systematically integrated published articles and DNA methylation microarray data
      to investigate the diagnostic performance of the APC methylation test for NSCLC.
      Two thousand two hundred and fifty-nine NSCLC tumor samples and 1,039 controls
      were collected from 17 published studies and TCGA NSCLC data. The association
      between APC promoter methylation and NSCLC was evaluated in a meta-analysis. An
      independent DNA methylation microarray dataset from TCGA project, in which five
      CpG sites located in the promoter region of APC were involved, was used to
      validate the results of the meta-analysis. RESULTS: A significant association was
      observed between APC promoter hypermethylation and NSCLC, with an aggregated odds
      ratio (OR) of 3.79 (95% CI: 2.22 to 6.45) in a random effects model. Pooled
      sensitivity and specificity were 0.548 (95% CI: 0.42 to 0.67, P < 0.0001) and
      0.776 (95% CI: 0.62 to 0.88, P < 0.0001), respectively. Each of the five CpG
      sites was much better in prediction (area under the curve, AUC: 0.71 to 0.73) in
      lung adenocarcinoma (Ad) than in lung squamous cell carcinoma (Sc) (AUC: 0.45 to
      0.61). The AUCs of the logistic prediction model based on these five CpGs were
      0.73 and 0.60 for Ad and Sc, respectively. Integrated analysis indicated that CpG
      site location, heterogeneous or autogenous controls, and the proportion of
      adenocarcinoma in samples were the most significant heterogeneity sources.
      CONCLUSIONS: The methylation status of APC promoter was strongly associated with
      NSCLC, especially adenocarcinoma. The APC methylation test could be applied in
      the clinical diagnosis of lung adenocarcinoma.

PMID- 24661339
TI  - Concordance with recommended postdischarge care guidelines among children with
      food-induced anaphylaxis.
AB  - OBJECTIVE: To describe patient characteristics, concordance with recommended
      postdischarge care, and risk of repeat events within a cohort of children
      discharged from an emergency department (ED) or hospital for food-induced
      anaphylaxis in the US. STUDY DESIGN: Children (aged <18 years) with an ED
      visit/hospitalization for food-induced anaphylaxis were identified from the 2002
      2008 Truven Health MarketScan databases using an expanded International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code
      algorithm. The initial identified ED visit/hospitalization was the index event.
      Claims data for the children with continuous medical and prescription coverage
      for >=1 year before and after the index event were evaluated. Analyses included
      the rates of 1-year postdischarge epinephrine autoinjector (EAI) prescription
      fills, allergist/immunologist visits, and repeat events. RESULTS: The study
      cohort comprised 1009 patients with an average age of 7 years, including 58%
      males, 27% with a history of asthma, and 90% discharged from an ED. Within 1 year
      postdischarge, 83% had an EAI prescription fill (69% within 1 week
      postdischarge), 43% had a specialist visit (51% within 4 weeks postdischarge),
      and 6.4% had evidence of another anaphylaxis-related ED visit/hospitalization.
      CONCLUSION: Among children with food-induced anaphylaxis, within 1 year
      postdischarge from the ED or hospital, concordance was higher for EAI
      prescription fills than for allergist/immunologist visits. Subsequent ED
      visits/hospital stays for anaphylactic events were low. More research is needed
      to identify barriers between recommendations and physician/patient behaviors, as
      well as the impact of not following the recommendations on patient outcomes and
      healthcare costs.

PMID- 24661341
TI  - A risk of sensory deprivation in the neonatal intensive care unit.

PMID- 24661340
TI  - Risk factors for first cerebrospinal fluid shunt infection: findings from a multi
      center prospective cohort study.
AB  - OBJECTIVE: To quantify the extent to which cerebrospinal fluid (CSF) shunt
      revisions are associated with increased risk of CSF shunt infection, after
      adjusting for patient factors that may contribute to infection risk. STUDY
      DESIGN: We used the Hydrocephalus Clinical Research Network registry to assemble
      a large prospective 6-center cohort of 1036 children undergoing initial CSF shunt
      placement between April 2008 and January 2012. The primary outcome of interest
      was first CSF shunt infection. Data for initial CSF shunt placement and all
      subsequent CSF shunt revisions prior to first CSF shunt infection, where
      applicable, were obtained. The risk of first infection was estimated using a
      multivariable Cox proportional hazard model accounting for patient
      characteristics and CSF shunt revisions, and is reported using hazard ratios
      (HRs) with 95% CI. RESULTS: Of the 102 children who developed first infection
      within 12 months of placement, 33 (32%) followed one or more CSF shunt revisions.
      Baseline factors independently associated with risk of first infection included:
      gastrostomy tube (HR 2.0, 95% CI, 1.1, 3.3), age 6-12 months (HR 0.3, 95% CI,
      0.1, 0.8), and prior neurosurgery (HR 0.4, 95% CI, 0.2, 0.9). After controlling
      for baseline factors, infection risk was most significantly associated with the
      need for revision (1 revision vs none, HR 3.9, 95% CI, 2.2, 6.5; >=2 revisions,
      HR 13.0, 95% CI, 6.5, 24.9). CONCLUSIONS: This study quantifies the elevated risk
      of infection associated with shunt revisions observed in clinical practice. To
      reduce risk of infection risk, further work should optimize revision procedures.

PMID- 24661342
TI  - Factors influencing response enthusiasm to telephone follow-up in patients with
      oesophageal carcinoma after oesophagectomy.
AB  - Response enthusiasm to telephone follow-up is a precondition for obtaining
      exhaustive information; however, no study has yet examined this specific issue.
      This study aimed to investigate possible factors influencing response enthusiasm
      to telephone follow-up in patients with oesophageal carcinoma after
      oesophagectomy and to propose corresponding countermeasures. A telephone follow
      up was conducted on patients who underwent oesophagectomy. The possible factors
      influencing response enthusiasm grades were investigated by univariate and
      logistic regression analyses. The study enrolled 346 eligible patients.
      Univariate analysis showed that the tumour, nodes, metastasis (TNM) staging (P =
      0.004); survival status (P < 0.001); survival time (P < 0.001); complications/co
      morbidities (P = 0.001); and the relationship between the patient and his/her
      contact person (P < 0.001) were significantly different among the three groups.
      The first group of patients had high response enthusiasm, the second group had
      moderate response enthusiasm, and the third group had low response enthusiasm.
      Logistic regression analysis demonstrated that only the complications/co
      morbidities [confidence interval (CI) = -2.310 to -0.665, P < 0.001] and
      dysphagia status (CI = 0.039-1.509, P = 0.039) were independent factors affecting
      the response enthusiasm grades. The primary therapeutic results and the current
      complications and co-morbidities, especially the dysphagia status, were important
      factors influencing response enthusiasm grades. Planning a follow-up schedule
      with proper health instructions could be crucial to the quality of follow-up. 

PMID- 24661343
TI  - Predicting weaning and extubation outcomes in long-term mechanically ventilated
      patients using the modified Burns Wean Assessment Program scores.
AB  - BACKGROUND AND OBJECTIVE: A number of clinical factors play pivotal roles in
      weaning and successful extubation of patients requiring long-term mechanical
      ventilator (LTMV) support. Many patients fail extubation even after passing
      weaning protocols and spontaneous breathing trials. This study aimed to assess
      the effectiveness of using a modified Burns Wean Assessment Program (m-BWAP)
      scoring instrument to predict extubation outcome in patients requiring LTMV.
      METHODS: All patients with a diagnostic coding for respiratory failure requiring
      LTMV for longer than 21 days over a 5-year period in a single centre (total 527
      patients) were included. Advanced practice nurses trained in the use of the m
      BWAP scored the items according to standard definitions. All patients were weaned
      by pressure support weaning and spontaneous breathing trails. Patients were
      divided into successful and unsuccessful groups according to the weaning and
      extubation outcomes. Baseline data, traditional weaning parameters and m-BWAP of
      the groups were analysed. The sensitivity and specificity of m-BWAP for
      predicting successful extubation were calculated. RESULTS: Of the 527 patients
      included, 145 (27.5%) had successful weaning trials. Of the 130 patients
      extubated, 102 (78.5%) had successful extubation. The m-BWAP score was higher in
      the patients with successful weaning trials and successful extubation outcome.
      Using a cut-off value of 60, the sensitivity and specificity of the m-BWAP to
      predict successful extubation were 81.4% and 82.1%, respectively. This was better
      than traditional weaning parameters. CONCLUSIONS: The m-BWAP is a good predictor
      for weaning and extubation outcome in patients requiring LTMV for longer than 21
      days.

PMID- 24661344
TI  - Surgical treatment of infective endocarditis in active intravenous drug users: a
      justified procedure?
AB  - BACKGROUND: Infective endocarditis is a life threatening complication of
      intravenous drug abuse, which continues to be a major burden with inadequately
      characterised long-term outcomes. We reviewed our institutional experience of
      surgical treatment of infective endocarditis in active intravenous drug abusers
      with the aim of identifying the determinants long-term outcome of this distinct
      subgroup of infective endocarditis patients. METHODS: A total of 451 patients
      underwent surgery for infective endocarditis between January 1993 and July 2013
      at the University Hospital of Heidelberg. Of these patients, 20 (7 female, mean
      age 35 +/- 7.7 years) underwent surgery for infective endocarditis with a history
      of active intravenous drug abuse. Mean follow-up was 2504 +/- 1842 days. RESULTS:
      Staphylococcus aureus was the most common pathogen detected in preoperative blood
      cultures. Two patients (10%) died before postoperative day 30. Survival at 1, 5
      and 10 years was 90%, 85% and 85%, respectively. Freedom from reoperation was
      100%. Higher NYHA functional class, higher EuroSCORE II, HIV infection, longer
      operating time, postoperative fever and higher requirement for red blood cell
      transfusion were associated with 90-day mortality. CONCLUSIONS: In active
      intravenous drug abusers, surgical treatment for infective endocarditis should be
      performed as extensively as possible and be followed by an aggressive
      postoperative antibiotic therapy to avoid high mortality. Early surgical
      intervention is advisable in patients with precipitous cardiac deterioration and
      under conditions of staphylococcal endocarditis. However, larger studies are
      necessary to confirm our preliminary results.

PMID- 24661345
TI  - Sustaining motivational interviewing: a meta-analysis of training studies.
AB  - BACKGROUND AND AIMS: Previous research indicates that motivational interviewing
      (MI) skills decline over time among participants in training workshops when post
      workshop feedback and coaching are not provided. This study explored moderators
      of skill retention among trainees learning MI mainly for substance use disorder
      treatment in real-world treatment settings, including workshop enhancements and
      type and dose of post-workshop feedback and coaching. METHODS: A meta-analysis of
      training studies was conducted with studies that reported MI skills using
      observational measures and that included trainees from real-world agency
      settings. Standardized change scores were calculated to indicate the magnitude of
      pre-post training change in MI skills; standardized change scores from post
      training to 3 and 6+ months follow-up were calculated to indicate the
      sustainability of training gains over time. Effect sizes were aggregated using
      random effects models. RESULTS: Twenty-one papers that reported the effects of MI
      training on agency staff were included in this review. Across studies, training
      yielded gains in MI skills (d = 0.76). Studies that did not include feedback
      and/or coaching reported eroding skills over a 6-month follow-up (d = -0.30),
      whereas post-workshop feedback/coaching sustained skills (d = 0.03). Effects of
      post-workshop feedback/coaching were moderated by frequency, duration and length
      of training. Moreover, studies reporting low levels of attrition from training
      protocols showed small increases in skills over the 6-month follow-up period (d =
      0.12), whereas studies with high attrition showed skill erosion (d = -0.29).
      CONCLUSIONS: On average, three to four feedback/coaching sessions over a 6-month
      period sustain skills among trainees for motivational interviewing, mainly for
      substance use disorder treatment. However, high rates of attrition from
      feedback/coaching contributes to post-workshop skill erosion.

PMID- 24661346
TI  - [Economic crisis and mental health. SESPAS report 2014].
AB  - Studies published before the financial crisis of 2008 suggest that economic
      difficulties contribute to poorer mental health. The IMPACT study conducted in
      primary health care centers in Spain found a significant increase in common
      mental disorders. Between 2006 and 2010, mood disorders increased by 19%, anxiety
      disorders by 8% and alcohol abuse disorders by 5%. There were also gender
      differences, with increased alcohol dependence in women during the crisis period.
      The most important risk factor for this increase was unemployment. In parallel,
      antidepressant consumption has increased in recent years, although there has not
      been a significant inrease in the number of suicides. Finally, the study offers
      some proposals to reduce the impact of the crisis on mental health: increased
      community services, employment activation measures, and active policies to reduce
      alcohol consumption and prevent suicidal behavior, particularly among young
      people. 

PMID- 24661347
TI  - Revisiting a non-significant findings study: a parent mentor intervention trial
      as exemplar.
AB  - The purpose of this paper is to describe an interactive process for revising a
      parent social support intervention study with non-significant quantitative
      findings but strong clinical significance. We will present the methodological
      challenges that were problematic in the original intervention that potentially
      contributed to the non-significant findings, and a revised plan of action for
      conducting a future parent social support intervention. Of note, we have
      reconsidered the theory used to frame the original study, the randomization
      process, the intervention clarity and fidelity plan, what measures would better
      capture the effect, and the development of a more robust analysis plan that
      considers intra-family correlation, mediation and moderation (mixed model
      analysis). We will present the revision for each of these methods supported by
      recent empirical literature. Although this process may not be appropriate for all
      non-significant interventions, it should be considered with any study that has
      clinical significance. 

PMID- 24661348
TI  - Assessment of spontaneous platelet aggregation using laser light scattering in
      healthy subjects: an attempt to standardize.
AB  - INTRODUCTION: When measuring platelet aggregation using laser light scattering,
      small aggregates forming without the addition of agonists may be observed. This
      event is called 'spontaneous platelet aggregation (SPA)'. The platelet
      hyperactivity observed in arterial thrombotic diseases can be detected with
      relative ease by measuring SPA. Standardization is urgently needed because of
      differences between measurement conditions among various laboratories. METHODS:
      We conducted a systematic study of factors that affect SPA measurement, compared
      SPA results to flow cytometry detection of surface antigens expressed on
      activated platelet membranes (P-selectin, activated glycoprotein IIb/IIIa), and
      determined conditions that yield stable measurements. RESULTS AND CONCLUSIONS: We
      evaluated results from 125 healthy volunteers and established conditions for a
      stable measurement of SPA. As the occurrence of SPA tended to increase with age,
      we determined conditions valid for subjects aged 20-60 years. Blood should be
      collected using a syringe, and the sample should be prepared after allowing the
      whole blood to rest for 30 min after collection. To isolate platelet-rich plasma,
      a 2-mL tube should be used and centrifuged at 150 g. The sample should be stored
      at room temperature, the platelet count of the sample should be (250 +/- 10) *
      10(9) /L, and the measurement should be completed within 90 min of blood
      collection.

PMID- 24661349
TI  - Cuneus and fusiform cortices thickness is reduced in trigeminal neuralgia.
AB  - BACKGROUND: Chronic pain disorders are presumed to induce changes in brain grey
      and white matters. Few studies have focused CNS alterations in trigeminal
      neuralgia (TN). METHODS: The aim of this study was to explore changes in white
      matter microstructure in TN subjects using diffusion tensor images (DTI) with
      tract-based spatial statistics (TBSS); and cortical thickness changes with
      surface based morphometry. Twenty-four patients with classical TN (37-67 y-o) and
      24 healthy controls, matched for age and sex, were included in the study.
      RESULTS: Comparing patients with controls, no diffusivity abnormalities of brain
      white matter were detected. However, a significant reduction in cortical
      thickness was observed at the left cuneus and left fusiform cortex in the
      patients group. The thickness of the fusiform cortex correlated negatively with
      the carbamazepine dose (p = 0.023). CONCLUSIONS: Since the cuneus and the
      fusiform gyrus have been related to the multisensory integration area and
      cognitive processing, as well as the retrieval of shock perception conveyed by
      Adelta fibers, our results support the role of these areas in TN pathogenesis.
      Whether such changes occurs as an epiphenomenon secondary to daily stimulation or
      represent a structural predisposition to TN in the light of peripheral vascular
      compression is a matter of future studies.

PMID- 24661350
TI  - The construct validity and responsiveness of the EQ-5D, SF-6D and Diabetes Health
      Profile-18 in type 2 diabetes.
AB  - BACKGROUND: Interest in the measurement of health related quality of life and
      psychosocial functioning from the patient's perspective in diabetes mellitus has
      grown in recent years. The aim of this study is to investigate the psychometric
      performance of and agreement between the generic EQ-5D and SF-6D and diabetes
      specific DHP-18 in Type 2 diabetes. This will support the future use of the
      measures by providing further evidence regarding their psychometric properties
      and the conceptual overlap between the instruments. The results will inform
      whether the measures can be used with confidence alongside each other to provide
      a more holistic profile of people with Type 2 diabetes. METHODS: A large
      longitudinal dataset (n = 1,184) of people with Type 2 diabetes was used for the
      analysis. Convergent validity was tested by examining correlations between the
      measures. Known group validity was tested across a range of clinical and diabetes
      severity indicators using ANOVA and effect size statistics. Agreement was
      examined using Bland-Altman plots. Responsiveness was tested by examining floor
      and ceiling effects and standardised response means. RESULTS: Correlations
      between the measures indicates that there is overlap in the constructs assessed
      (with correlations between 0.1 and 0.7 reported), but there is some level of
      divergence between the generic and condition specific instruments. Known group
      validity was generally good but was not consistent across all indicators included
      (with effect sizes from 0 to 0.74 reported). The EQ-5D and SF-6D displayed a high
      level of agreement, but there was some disagreement between the generic measures
      and the DHP-18 dimensions across the severity range. Responsiveness was higher in
      those who self-reported change in health (SRMs between 0.06 and 0.25).
      CONCLUSIONS: The psychometric assessment of the relationship between the EQ-5D,
      SF-6D and DHP-18 shows that all have a level of validity for use in Type 2
      diabetes. This suggests that the measures can be used alongside each other to
      provide a more holistic assessment of with the quality of life impacts of Type 2
      diabetes.

PMID- 24661351
TI  - Radioiodinated and astatinated NHC rhodium complexes: synthesis.
AB  - INTRODUCTION: The clinical development of radioimmunotherapy with astatine-211 is
      limited by the lack of a stable radiolabeling method for antibody fragments. An
      astatinated N-heterocyclic carbene (NHC) Rhodium complex was assessed for the
      improvement of radiolabeling methodologies with astatine. METHODS: Wet harvested
      astatine-211 in diisopropyl ether was used. Astatine was first reduced with
      cysteine then was reacted with a chlorinated Rh-NHC precursor to allow the
      formation of the astatinated analogue. Reaction conditions have been optimized.
      Astatine and iodine reactivity were also compared. Serum stability of the
      astatinated complex has been evaluated. RESULTS: Quantitative formation of
      astatide was observed when cysteine amounts higher than 46.2 nmol/MUl of astatine
      solution were added. Nucleophilic substitution kinetics showed that high
      radiolabeling yields were obtained within 15 min at 60 degrees C (88%) or within
      5 min at 100 degrees C (95%). Chromatographic characteristics of this new
      astatinated compound have been correlated with the cold iodinated analog ones.
      The radioiodinated complex was also synthesized from the same precursor (5 min.
      at 100 degrees C, up to 85%) using [(125)I]NaI as a radiotracer. In vitro
      stability of the astatinated complex was controlled after 15 h incubation in
      human serum at 4 degrees C and 37 degrees C. No degradation was observed,
      indicating the good chemical and enzymatic stability. CONCLUSION: The astatinated
      complex was obtained in good yield and exhibited good chemical and enzymatic
      stability. These preliminary results demonstrate the interest of this new
      radiolabeling methodology, and further functionalizations should open new
      possibilities in astatine chemistry. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR
      PATIENT CARE: Although there are many steps and pitfalls before clinical use for
      a new prosthetic group from the family of NHC complexes, this work may open a new
      path for astatine-211 targeting.

PMID- 24661352
TI  - 2013 European guideline on the management of lymphogranuloma venereum.
AB  - WHAT IS NEW IN THIS UPDATED GUIDELINE?: This is the update version of the 2010
      European guideline on the management of lymphogranuloma venereum (LGV). New
      issues are: EPIDEMIOLOGY: Based on clonal relatedness of prevalent LGV strains
      there is evidence that the LGV epidemic among men who have sex with men (MSM) in
      the Western world prevailed already in the United States in the 1980s and was
      introduced into Europe by the end of the last century. AETIOLOGY AND
      TRANSMISSION: A new LGV variant causing severe proctitis was unveiled and
      designated L2c. The L2b LGV variant causing the vast majority of infections among
      MSM is now also found among a few heterosexual women. MANAGEMENT: Apart from HIV
      and STI screening, Hepatitis C Virus (HCV) testing should be offered to all LGV
      patients. To exclude reinfections, STI screening during a follow-up visit 3
      months after an LGV diagnosis should be offered.

PMID- 24661353
TI  - Effect of weight maintenance or gain in a 10 years period over telomere length,
      sirtuin 1 and 6 expression and carotid intima media thickness.
AB  - BACKGROUND: Lack of weight gain throughout adult life could mimic the beneficial
      effects of energy restriction in humans. The present study aimed to assess the
      effects of weight stability or gain, over a period of 10 years, on telomere
      length, sirtuin 1 and 6 expression, and carotid intima media thickness. METHODS:
      We studied 148 healthy adults (age range 20-59 years; 101 females) who had an
      objective record of their weight 10 years before. They were classified as weight
      losers, weight maintainers, weight gainers and extreme weight gainers. A fasting
      blood sample was obtained for routine laboratory and isolation of peripheral
      blood mononuclear cells, to extract DNA and RNA, and to measure telomere length
      and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was
      measured by ultrasound. Body composition was measured by Dual-energy X-ray
      absorptiometry. RESULTS: In the 10-year period, 24 participants lost weight (17
      females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34
      were extreme weight gainers (28 females). Female weight gainers had a higher body
      mass index, waist circumference, total body fat and homeostatic model assessment
      insulin resistance. Male weight gainers had a higher hip circumference and total
      body fat. No differences in telomere length, sirtuin 1 expression and carotid
      intima media thickness were observed between weight gainers and maintainers.
      CONCLUSIONS: No effect of weight maintenance or gain was observed on metabolic
      and vascular markers of ageing.

PMID- 24661354
TI  - Factors influencing polymerase chain reaction outcomes in patients with
      clinically suspected ocular tuberculosis.
AB  - BACKGROUND: Polymerase chain reaction (PCR) assay can be a useful method for
      definitive diagnosis in paucibacillary infections such as ocular tuberculosis
      (TB). In this study, we have evaluated factors affecting PCR outcomes in patients
      with clinically suspected ocular TB. Patients with clinically suspected ocular TB
      were investigated by PCR of aqueous or vitreous samples. Three control groups
      were also tested: group 1 included culture-proven non-tuberculous
      endophthalmitis, group 2 culture-negative non-tuberculous endophthalmitis, and
      group 3 patients undergoing surgery for uncomplicated cataract. PCR targeted one
      or more of following targets: IS6110, MPB64, and protein b genes of Mycobacterium
      tuberculosis complex. Multiple regression analysis (5% level of significance) was
      done to evaluate the associations between positive PCR outcome and laterality of
      disease, tuberculin skin test (TST)/interferon-gamma release assay (IGRA), chest
      radiography, and type of sample (aqueous or vitreous). The main outcome measures
      were positive PCR by one or more gene targets, and factors influencing positive
      PCR outcomes. RESULTS: All 114 samples were tested for MPB64, 110 for protein b,
      and 88 for IS6110. MPB64 was positive in 70.2% (n = 80) of tested samples,
      protein b in 40.0% (n = 44), and IS6110 in only 9.1% (n = 8). DNA sequencing of
      amplicons from four randomly chosen PCR reactions showed homology for M.
      tuberculosis complex. Of the 80 PCR-positive patients, 71 completed a full course
      of antitubercular therapy, of which 65 patients (91.5%) had complete resolution
      of inflammation at final follow-up. Among controls, 12.5% (3 out of 24) in group
      1 and 18.7% (6 out of 32) in group 2 also tested positive by PCR. No PCR-positive
      outcome was observed in control group 3 (n = 25). Multiple regression analysis
      revealed significant association of positive PCR outcome with bilateral
      presentation, but not with a positive TST/IGRA, chest radiography, or type of
      sample (aqueous/vitreous) used. CONCLUSIONS: Careful selection of gene targets
      can yield high PCR positivity in clinically suspected ocular TB. Bilateral
      disease presentation but not any evidence of latent systemic TB influences PCR
      outcomes. False-positive results may be seen in ocular inflammation unrelated to
      ocular TB.

PMID- 24661356
TI  - Clinical phenotypes of MAGEL2 mutations and deletions.

PMID- 24661357
TI  - Development and validation of a clinical risk score for predicting drug-resistant
      bacterial pneumonia in older Chinese patients.
AB  - BACKGROUND AND OBJECTIVE: Health care-associated pneumonia (HCAP) and drug
      resistant bacterial pneumonia may not share identical risk factors. We have shown
      that bronchiectasis, recent hospitalization and severe pneumonia (confusion,
      blood urea level, respiratory rate, low blood pressure and 65 year old (CURB-65)
      score >= 3) were independent predictors of pneumonia caused by potentially drug
      resistant (PDR) pathogens. This study aimed to develop and validate a clinical
      risk score for predicting drug-resistant bacterial pneumonia in older patients.
      METHODS: We derived a risk score by assigning a weighting to each of these risk
      factors as follows: 14, bronchiectasis; 5, recent hospitalization; 2, severe
      pneumonia. A 0.5 point was defined for the presence of other risk factors for
      HCAP. We compared the areas under the receiver-operating characteristics curve
      (AUROC) of our risk score and the HCAP definition in predicting PDR pathogens in
      two cohorts of older patients hospitalized with non-nosocomial pneumonia.
      RESULTS: The derivation and validation cohorts consisted of 354 and 96 patients
      with bacterial pneumonia, respectively. PDR pathogens were isolated in 48 and 21
      patients in the derivation and validation cohorts, respectively. The AUROCs of
      our risk score and the HCAP definition were 0.751 and 0.650, respectively, in the
      derivation cohort, and were 0.782 and 0.671, respectively, in the validation
      cohort. The differences between our risk score and the HCAP definition reached
      statistical significance. A score >= 2.5 had the best balance between sensitivity
      and specificity. CONCLUSIONS: Our risk score outperformed the HCAP definition to
      predict pneumonia caused by PDR pathogens. A history of bronchiectasis or recent
      hospitalization is the major indication of starting empirical broad-spectrum
      antibiotics.

PMID- 24661355
TI  - Cardiovascular effects of cholecalciferol treatment in dialysis patients--a
      randomized controlled trial.
AB  - BACKGROUND: Patients on chronic dialysis are at increased risk of vitamin D
      deficiency. In observational studies plasma 25-hydroxyvitamin D (p-25(OH) D)
      levels are inversely correlated with plasma BNP and adverse cardiovascular
      outcomes. Whether a causal relation exists has yet to be established. The aim of
      this study was to test the hypothesis that cholecalciferol supplementation
      improves cardiac function and reduces blood pressure (BP) and pulse wave velocity
      (PWV) in patients on chronic dialysis. METHODS: In a randomized, placebo
      controlled, double-blind study, we investigated the effect of 75 MUg (3000 IU)
      cholecalciferol daily for 6 months, in patients on chronic dialysis. We performed
      two-dimensional echocardiography, with doppler and tissue-doppler imaging, 24-h
      ambulatory BP (24-h BP), PWV, augmentation index (AIx), central BP (cBP) and
      brain natriuretic peptide (BNP) measurements at baseline and after 6 months.
      RESULTS: Sixty-four patients were allocated to the study. Fifty dialysis patients
      with a mean age of 68 years (range: 46-88) and baseline p-25(OH) D of 28 (20;53)
      nmol/l completed the trial. Cholecalciferol increased left ventricular (LV)
      volume, but had no impact on other parameters regarding LV structure or left
      atrial structure. LV systolic function, LV diastolic function, PWV, cBP, AIx and
      BNP were not changed in placebo or cholecalciferol group at follow-up. 24-h BP
      decreased significantly in placebo group and tended to decrease in
      cholecalciferol group without any difference between treatments. CONCLUSION: Six
      months of cholecalciferol treatment in patients on chronic dialysis did not
      improve 24-h BP, arterial stiffness or cardiac function. TRIAL REGISTRATION:
      NCT01312714, Registration Date: March 9, 2011.

PMID- 24661358
TI  - Translation and psychometric assessment of the Persian version of the Rhodes
      Index of Nausea, Vomiting and Retching (INVR) scale for the assessment of
      chemotherapy-induced nausea and vomiting.
AB  - No tools are available to assess or measure the experience of chemotherapy
      induced nausea and vomiting (CINV) for Persian/Farsi speakers. The purpose of
      this study is to translate the Rhodes Index of Nausea, Vomiting and Retching
      (INVR) scale for use with Persian-speaking cancer patients. A sample of 94 cancer
      patients were recruited from a cancer research centre in Mashhad-Iran. A standard
      two phase process of scale translation and validation was conducted. In phase I,
      standard 'forward-backward' translation procedure was used to translate the
      original version of the INVR questionnaire into Persian. The translated
      questionnaire was reviewed and revised and a Persian version of the scale was
      produced. In the second phase, a multiphase instrumentation study describing the
      internal consistency and test-retest reliability of the translated version was
      conducted. The inter-item correlation measured by Cronbach's alpha was 0.88.
      Test/re-test reliability was measured by the weighted kappa and was between 0.63
      and 0.79, indicating 'substantial agreement' and stability between the initial
      and subsequent administrations for each item. These results demonstrate that the
      Persian version of the INVR is acceptable for use among Iranian cancer patients.
      Researchers could use this study as a model for future translation and
      application of psychometric instrumentation. 

PMID- 24661359
TI  - Immunolocalization of AQP5 in resting and stimulated normal labial glands and in
      Sjogren's syndrome.
AB  - OBJECTIVE: In our current work, in vivo examination of AQP5 distribution in
      labial salivary glands following stimulation of secretion has been carried out in
      normal individuals and in patients with Sjogren's syndrome. SUBJECTS AND METHODS:
      For this study, we selected five patients with primary Sjogren's syndrome (mean
      age 62.4 +/- 10.6 s.d. years) diagnosed in accordance with the European
      Cooperative Community classification criteria. There were five patients (mean age
      27 +/- 2.5 s.d. years) in the control group. The subcellular distribution of AQP5
      in human labial gland biopsies was determined with light and immunoelectron
      microscopy before and 30 min after administration of oral pilocarpine. RESULTS:
      In unstimulated control and Sjogren's labial glands, AQP5 is about 90% localized
      in the apical plasma membrane, with only rarely associated gold particles with
      intracellular membrane structures. We have found no evidence of pilocarpine
      induced changes in localization of AQP5 in either healthy individuals or patients
      with Sjogren's syndrome. CONCLUSIONS: Our studies indicate that neither Sjogren's
      syndrome itself, nor muscarinic cholinergic stimulation in vivo caused any
      significant changes in the distribution of AQP5 in the labial salivary gland
      cells.

PMID- 24661360
TI  - An im-perfect storm.

PMID- 24661361
TI  - The utility of and risks associated with the use of spontaneous volunteers in
      disaster response: a survey.
AB  - OBJECTIVE: The use of spontaneous volunteers (SV) is common after a disaster, but
      their limited training and experience can create a danger for the SVs and
      nongovernmental voluntary organizations (NVOs). We assessed the experience of
      NVOs with SVs during disasters, how they were integrated into the agency's
      infrastructure, their perceived value to previous responses, and liability issues
      associated with their use. METHODS: Of the 51 National Voluntary Organizations
      Active in Disasters organizations that were contacted for surveys, 24 (47%)
      agreed to participate. RESULTS: Of the 24 participating organizations, 19 (72%)
      had encountered SVs during a response, most (79%) used them regularly, and 68%
      believed that SVs were usually useful. SVs were always credentialed by 2
      organizations, and sometimes by 6 (31%). One organization always performed
      background checks; 53% provided just-in-time training for SVs; 26% conducted
      evaluations of SV performance; and 21% provided health or workers compensation
      benefits. Two organizations reported an SV death; 42% reported injuries; 32%
      accepted legal liability for the actions of SVs; and 16% were sued because of
      actions by SVs. CONCLUSIONS: The use of SVs is widespread, but NVOs are not
      necessarily structured to incorporate them effectively. More structured efforts
      to integrate SVs are critical to safe and effective disaster response.

PMID- 24661362
TI  - Enhancing the translation of disaster health competencies into practice.
AB  - OBJECTIVES: Disaster health workers currently have no common standard based on a
      shared set of competencies, learning objectives, and performance metrics with
      which to develop courses or training materials relevant to their learning
      audience. We examined how existing competency sets correlate within the 2012
      pyramidal learning framework of competency sets in disaster medicine and public
      health criteria and describe how this exercise can guide curriculum developers.
      METHODS: We independently categorized 35 disaster health-related competency sets
      according to the 4 levels and criteria of the pyramidal learning framework of
      competency sets in disaster medicine and public health. RESULTS: Using the
      hierarchical learning framework of competency sets in disaster medicine and
      public health criteria as guidance, we classified with consistency only 10 of the
      35 competency sets. CONCLUSIONS: The proposed series of minor modifications to
      the framework should allow for consistent classification of competency sets.
      Improved education and training of all health professionals is a necessary step
      to ensuring that health system responders are appropriately and adequately primed
      for their role in disasters. Revising the organizing framework should assist
      disaster health educators in selecting competencies appropriate to their learning
      audience and identify gaps in current education and training.

PMID- 24661363
TI  - Val/Leu247 polymorphism of beta2-glycoprotein I and thrombosis in Chinese
      patients with SLE.
AB  - INTRODUCTION: To determine the polymorphism at position 247 of the beta2
      glycoprotein I (beta2GPI) gene in patients with systemic lupus erythematosus
      (SLE) and healthy controls in the Chinese Han Population and elucidate the
      relationship between beta2GPI polymorphisms and anti-beta2GPI levels, and
      furthermore investigate the correlation between beta2GPI polymorphisms and
      thrombosis in patients with SLE. METHODS: The beta2GPI polymorphisms of 300
      patients with SLE and 300 healthy controls were examined by single-specific
      primer polymerase chain reaction (SSP-PCR), the efficacy of which was confirmed
      by sequencing technology. Anti-beta2GPI antibodies were tested by enzyme-linked
      immunosorbent assay. beta2GPI polymorphisms associated with thrombosis and the
      presence of anti-beta2GPI antibodies were also statistically evaluated with SPSS
      software. RESULTS: The genotype expressions and the allele frequencies were
      obtained in both patients with SLE and healthy controls. The SLE patients with
      thrombosis had significantly higher frequencies of the VV genotype and V allele
      than those without thrombosis and the controls, and there were no differences in
      VV genotype and V allele expression between the SLE patients without thrombosis
      and the controls. In contrast, the presence of anti-beta2GPI antibody was related
      to the VV genotype of beta2GPI, and the anti-beta2GPI-positive patients had
      obviously higher frequencies of the VV genotype than the negative ones and the
      controls. CONCLUSION: The study results suggested that the V/V genotype and the V
      encoding allele at position 247 of the beta2GPI gene had strong correlation with
      the occurrence of thrombosis and the production of the anti-beta2GPI antibodies,
      showing that the Val(247) beta2GPI allele may be one of the genetic risk factors
      for the development of thrombosis in patients with SLE.

PMID- 24661364
TI  - Influence of different toothpaste abrasives on the bristle end-rounding quality
      of toothbrushes.
AB  - OBJECTIVES: To evaluate the influence of different toothpaste abrasives on the
      bristle wear and bristle tip morphology of toothbrushes with different degrees of
      hardness. MATERIAL AND METHODS: Ninety samples of bovine incisor teeth were used
      in this study. The samples were randomly divided into three groups according to
      the bristle hardness of the toothbrush used: soft bristles (S); extra-soft
      bristles (ES); hard bristles (H). The toothbrushes of each group were randomly
      divided into six subgroups with five toothbrushes each, according to the abrasive
      of the toothpaste used in the simulation: Negative control (distilled water);
      toothpaste 1 (silica); toothpaste 2 (hydrated silica); toothpaste 3 (calcium
      carbonate, calcium bicarbonate and silica); toothpaste 4 (tetrapotassium
      pyrophosphate, silica and titanium dioxide); toothpaste 5 (calcium carbonate).
      The samples were placed in a toothbrushing simulating machine that simulating
      three months of brushing. The toothbrush bristles were evaluated by the bristle
      wear index, and the bristle tips morphology was evaluated by the bristle tip
      morphology index. RESULTS: The ES brush presented the highest bristle wear among
      the toothbrushes. Additionally, the S brushes showed better morphology of the
      bristles followed by ES and H brushes. The type of abrasive only influenced the
      bristle tip morphology of the ES brushes. The toothpaste 3 induced the worse
      bristle tip morphology than all the other toothpastes. CONCLUSIONS: Different
      abrasives have influence only on the bristle tip morphology of the ES brushes.

PMID- 24661365
TI  - An intervention to improve inpatient medication management: a before and after
      study.
AB  - AIM: To optimise medication administration, prevent medication errors and improve
      inpatient safety. BACKGROUND: Interventions are needed to reduce medication
      related errors and to improve patient safety. METHOD: A five-point management
      intervention strategy was developed and implemented. A quasi-experimental design
      was used to examine its effects. RESULTS: Comparing pre-intervention data with
      post-intervention data, the rate of accurate compliance with medication policies
      and procedures increased from 86.7% (645/744 doses observed) to 97.5% (725/744).
      The success rate of medication administration procedures increased from 94.0%
      (466/496 doses observed) to 96.8% (480/496). Nurse-initiated medication error
      reports/total medication error reports increased from 77.1% (101/131) to 95.1%
      (58/61). Rate of inpatient satisfaction with medication increased from 92.1%
      (3427/3720) to 98.3% (3656/3720). Complaints related to nursing medication
      administration decreased from 23 to 6 (73.9% reduction). CONCLUSION: The five
      point management intervention strategy improved inpatient medication safety:
      medication errors were reduced, nurses' awareness and skills of medication safety
      enhanced, inpatient satisfaction improved. However, randomised controlled trials
      are needed to test its effectiveness. IMPLICATIONS FOR NURSING MANAGEMENT: A
      systematic approach is vital to address the issues of medication errors and
      patient safety.

PMID- 24661366
TI  - The extent of linkage disequilibrium in beef cattle breeds using high-density SNP
      genotypes.
AB  - BACKGROUND: The extent of linkage disequilibrium (LD) between molecular markers
      impacts genome-wide association studies and implementation of genomic selection.
      The availability of high-density single nucleotide polymorphism (SNP) genotyping
      platforms makes it possible to investigate LD at an unprecedented resolution. In
      this work, we characterised LD decay in breeds of beef cattle of taurine,
      indicine and composite origins and explored its variation across autosomes and
      the X chromosome. FINDINGS: In each breed, LD decayed rapidly and r2 was less
      than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into
      three groups of similar LD decay that distinguished the three main cattle types.
      At short distances between markers (<10 kb), taurine breeds showed higher LD
      (r2=0.45) than their indicine (r2=0.25) and composite (r2=0.32) counterparts.
      This higher LD in taurine breeds was attributed to a smaller effective population
      size and a stronger bottleneck during breed formation. Using all SNPs on only the
      X chromosome, the three cattle types could still be distinguished. However for
      taurine breeds, the LD decay on the X chromosome was much faster and the
      background level much lower than for indicine breeds and composite populations.
      When using only SNPs that were polymorphic in all breeds, the analysis of the X
      chromosome mimicked that of the autosomes. CONCLUSIONS: The pattern of LD
      mirrored some aspects of the history of breed populations and showed a sharp
      decay with increasing physical distance between markers. We conclude that the
      availability of the HD chip can be used to detect association signals that
      remained hidden when using lower density genotyping platforms, since LD dropped
      below 0.2 at distances of 50 kb.

PMID- 24661367
TI  - Management of congenital fourth cranial nerve palsy.

PMID- 24661368
TI  - No red reflexes and retrolental opacities in the newborn nursery.

PMID- 24661369
TI  - Spare the rod, spoil the degeneration.

PMID- 24661370
TI  - Smartphones, video display terminals, and dry eye disease in children.

PMID- 24661371
TI  - Natural history of valsalva retinopathy in an adolescent.

PMID- 24661372
TI  - Glycaemic responses of staple South Asian foods alone and combined with curried
      chicken as a mixed meal.
AB  - BACKGROUND: The glycaemic responses of staples differ when eaten as mixed meals.
      We determined the glycaemic responses and glycaemic index (GI) values for common
      South Asian carbohydrate rich foods and the effect of adding curried chicken to
      them as mixed meals. METHODS: The GI and glycaemic response to staples (basmati
      rice, pilau rice and chapatti) and mixed meals (pilau rice with chicken curry and
      chapatti with chicken curry) were measured in healthy volunteers. Paired
      comparisons in each subject were carried out for staples and their equivalent
      mixed meals (n = 9). RESULTS: GI values for the mixed meals were significantly
      lower than the staples alone (41 and 60 for pilau rice with chicken curry and
      pilau rice alone, P = 0.001; 45 and 68 for chapatti with chicken curry and
      chapatti alone, P = 0.004). Both, pilau rice and chapatti with chicken curry had
      a significantly lower glycaemic response than their equivalent staples alone:
      incremental area under the blood glucose response curves (IAUC) 111.9 mmol min(-1
      ) L(-1) for pilau rice with curry versus 162.4 mmol min(-1 ) L(-1) for pilau rice
      alone (P = 0.001) and IAUC 110.1 mmol min(-1 ) L(-1) for chapatti with chicken
      curry versus 183.6 mmol min(-1 ) L(-1) for chapatti alone (P = 0.002).
      CONCLUSIONS: Adding fat and protein-containing curries as part of a mixed meal to
      carbohydrate rich staple foods reduced glycaemic responses, and also changed the
      GI category.

PMID- 24661374
TI  - Zinc monotherapy is effective in Wilson's disease patients with mild liver
      disease diagnosed in childhood: a retrospective study.
AB  - BACKGROUND: Wilson's disease (WD) evolves rapidly and is fatal if untreated. The
      treatment of WD patients with mild liver disease is not clearly defined. To
      address this issue, we evaluated long-term outcomes of three treatment regimens
      (D-penicillamine, zinc or both) in patients diagnosed in childhood. METHODS: We
      retrospectively evaluated efficacy, compliance and reasons for treatment
      discontinuation in 42 WD patients (median age at diagnosis: 6 years; median
      follow-up: 12 years) with mild liver disease. Treatment duration for each
      treatment block until a medication change or completion of follow-up was
      analyzed. Events of change of treatment were evaluated using Kaplan-Meier
      analysis. RESULTS: Total discontinuations due to treatment failure or adverse
      events were more frequent in patients receiving D-penicillamine (45%) or
      combination (36%) therapy than in patients receiving zinc (12%) (P = .001 and P =
      .02, respectively). Treatment failure was more frequent on D-penicillamine (28%)
      and combination therapy (36%) than on zinc (12%); the difference was
      statistically significant only between zinc and combination therapy (P = .03).
      First-line zinc monotherapy controlled WD-related liver disease in 13/15 patients
      (87%); the two subjects that failed on zinc were poor adherent. Zinc was
      effective in 3/5 (60%) patients that failed on D-penicillamine and combination
      regimens. All 15 D-penicillamine responders that switched to zinc had good
      control of liver disease at a median follow-up of 13.1 years. Among 6 D
      penicillamine non-responders that switched to zinc, 4 (67%) responded. At follow
      up completion, only 5/42 (12%) patients failed. Adverse event-induced
      discontinuation was significantly more frequent in patients on D-penicillamine
      than in patients receiving zinc (P = .03). CONCLUSIONS: Zinc monotherapy is
      effective in controlling WD-related liver disease both as first-line and as
      maintenance treatment in patients with mild liver disease diagnosed in childhood.

PMID- 24661373
TI  - Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in
      cancer patients: a cross sectional study.
AB  - BACKGROUND: Impairment of cognitive functioning has been reported in several
      studies in patients treated with chemotherapy. So far, no studies have been
      published on the effects of the vascular endothelial growth factor receptor
      (VEGFR) inhibitors on cognitive functioning. We investigated the objective and
      subjective cognitive function of patients during treatment with VEGFR tyrosine
      kinase inhibitors (VEGFR TKI). METHODS: Three groups of participants, matched on
      age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or
      GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2.
      patients with mRCC not receiving systemic treatment (patient controls n = 20); 3.
      healthy controls (n = 30). Sixteen neuropsychological tests examining the main
      cognitive domains (intelligence, memory, attention and concentration, executive
      functions and abstract reasoning) were administered by a neuropsychologist. Four
      questionnaires were used to assess subjective cognitive complaints, mood, fatigue
      and psychological wellbeing. RESULTS: No significant differences in mean age, sex
      distribution, education level or IQ were found between the three groups. Both
      patient groups performed significantly worse on the cognitive domains Learning &
      Memory and Executive Functions (Response Generation and Problem Solving) compared
      to healthy controls. However only the VEGFR TKI patients showed impairments on
      the Executive subdomain Response Generation. Effect sizes of cognitive
      dysfunction in patients using VEGFR TKI were larger on the domains Learning &
      Memory and Executive Functions, compared to patient controls. Both patients
      groups performed on the domain Attention & Concentration the same as the healthy
      controls. Longer duration of treatment on VEGFR TKI was associated with a worse
      score on Working Memory tasks. CONCLUSIONS: Our data suggest that treatment with
      VEGFR TKI has a negative impact on cognitive functioning, specifically on
      Learning & Memory, and Executive Functioning. We propose that patients who are
      treated with VEGFR TKI are monitored and informed for possible signs or symptoms
      associated with cognitive impairment. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT01246843.

PMID- 24661375
TI  - A rare case of primary systemic amyloidosis presenting with multiorgan
      involvement.

PMID- 24661376
TI  - Insights into cancer surveillance in Central and Eastern Europe, Israel and
      Turkey.
AB  - The current cancer landscape within transitional economies in central and Eastern
      Europe and the Mediterranean area is not particularly optimistic. Current
      perceptions are often based on extrapolations from other countries and regions;
      and hence the authors collaborated with the South Eastern Europe Oncology Group
      (SEEROG) to collect information on cancer registration in Central and Eastern
      Europe, Israel and Turkey. Healthcare authorities and specialist oncology centres
      in 21 countries in the region were contacted for information on cancer registries
      in their countries. Based on this information, the authors believe that the
      recording and reporting of data on cancer in the region is at an acceptable
      level. The authors discuss and compare institution- and population-based
      registries, and present opinions on elements of an 'ideal registry' based on the
      survey replies and comparisons with other registries. A comparison with the
      sources used for GLOBOCAN 2008 illustrates the need for consistent data to be
      communicated, published and utilised throughout the region and the oncology
      community. The authors conclude by considering the potential value of
      collaboration between health authorities across the region, as well as between
      the clinical and epidemiological communities, to ensure that cancer data are
      consistently collected, verified and made public. 

PMID- 24661377
TI  - The use of core needle biopsy as first-line in diagnosis of thyroid nodules
      reduces false negative and inconclusive data reported by fine-needle aspiration.
AB  - BACKGROUND: The reported reliability of core needle biopsy (CNB) is high in
      assessing thyroid nodules after inconclusive fine-needle aspiration (FNA)
      attempts. However, first-line use of CNB for nodules considered at risk by
      ultrasonography (US) has yet to be studied. The aim of this study were: 1) to
      evaluate the potential merit of using CNB first-line instead of conventional FNA
      in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB
      and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of
      cancer. METHODS: Seventy-seven patients with a suspicious-appearing, recently
      discovered solid thyroid nodule were initially enrolled as study participants. No
      patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on
      study design, all patients were proposed to undergo CNB as first-line diagnostic
      aspiration, while those patients refusing to do so underwent conventional FNA.
      RESULTS: Five patients refused the study, and a total of 31 and 41 thyroid
      nodules were subjected to CNB and FNA, respectively. At follow-up, the overall
      rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic
      accuracy of CNB (97%) was significantly (P < 0.05) higher than that of FNA (78%).
      In one benign lesion, CNB was inconclusive. Four (12%) of the 34 cancers of the
      FNA group were not initially diagnosed because of false negative (N = 1),
      indeterminate (N = 2) or not adequate (N = 1) samples. CONCLUSIONS: CNB can
      reduce the false negative and inconclusive results of conventional FNA and should
      be considered a first-line method in assessing solid thyroid nodules at high risk
      of malignancy.

PMID- 24661378
TI  - Is nursing shortage in Israel inevitable?
AB  - Israel has a low density of professional nurses. New evidence suggests less than
      optimal hospital work environments may undermine efficient and effective delivery
      of nursing care and contribute to job dissatisfaction and nurse turnover among
      nurses who are in short supply. Potential approaches to address these challenges
      are discussed. 

PMID- 24661379
TI  - Measurement of oxygen concentration delivered via nasal cannulae by tracheal
      sampling.
AB  - BACKGROUND AND OBJECTIVE: Oxygen is used in many clinical scenarios, however the
      variable performance of nasal cannulae makes determining the precise fraction of
      inspired oxygen (FiO2 ) difficult. We developed a novel method for measurement of
      the tracheal FiO2 using a catheter placed via bronchoscopy. We investigate the
      effects of oxygen delivery, respiratory rate, mouth position and estimated minute
      ventilation (VE ) on the FiO2 delivered by nasal cannulae. METHODS: The catheter
      was placed in 20 subjects. Tracheal gas concentrations were analysed during six 5
      min treatments controlling for oxygen delivery rate, respiratory rate and mouth
      position. Ventilation was monitored with respiratory inductive plethysmography
      (RIP). The FiO2 delivered by nasal cannulae was compared between treatments, and
      we investigated the relationships among the FiO2 , alveolar partial pressure of
      oxygen (PA O2 ) and VE . RESULTS: The FiO2 increased by 0.038/L/min of oxygen.
      Respiratory rate had a significant effect on the FiO2 . A normal respiratory rate
      of 15 breaths/min and oxygen supplementation via nasal cannula at 2 L/min
      resulted in an FiO2 of 0.296; however, FiO2 decreased by 0.012 at 20 breaths/min
      and 0.004 at 10 breaths/min. The mean FiO2 decreased by 0.024 with the mouth
      open. The FiO2 and PA O2 were observed to decrease with increasing VE .
      CONCLUSIONS: Continuous measurement of the FiO2 using a transtracheal catheter
      provides detailed insight into inspiratory changes of the FiO2 delivered by nasal
      cannulae. Our study confirms that respiratory rate, VE and mouth position
      significantly influence the inspired oxygen concentration. These parameters
      should be accounted for when prescribing oxygen.

PMID- 24661380
TI  - Serotonin2C receptors modulate dopamine transmission in the nucleus accumbens
      independently of dopamine release: behavioral, neurochemical and molecular
      studies with cocaine.
AB  - In keeping with its ability to control the mesoaccumbens dopamine (DA) pathway,
      the serotonin2C receptor (5-HT2C R) plays a key role in mediating the behavioral
      and neurochemical effects of drugs of abuse. Studies assessing the influence of 5
      HT2C R agonists on cocaine-induced responses have suggested that 5-HT2C Rs can
      modulate mesoaccumbens DA pathway activity independently of accumbal DA release,
      thereby controlling DA transmission in the nucleus accumbens (NAc). In the
      present study, we assessed this hypothesis by studying the influence of the 5
      HT2C R agonist Ro 60-0175 on cocaine-induced behavioral, neurochemical and
      molecular responses. The i.p. administration of 1 mg/kg Ro 60-0175 inhibited
      hyperlocomotion induced by cocaine (15 mg/kg, i.p.), had no effect on cocaine
      induced DA outflow in the shell, and increased it in the core subregion of the
      NAc. Furthermore, Ro 60-0175 inhibited the late-onset locomotion induced by the
      subcutaneous administration of the DA-D2 R agonist quinpirole (0.5 mg/kg), as
      well as cocaine-induced increase in c-Fos immunoreactivity in NAc subregions.
      Finally, Ro 60-0175 inhibited cocaine-induced phosphorylation of the DA and c-AMP
      regulated phosphoprotein of Mr 32 kDa (DARPP-32) at threonine residues in the NAc
      core, this effect being reversed by the selective 5-HT2C R antagonist SB 242084
      (0.5 mg/kg, i.p.). Altogether, these findings demonstrate that 5-HT2C Rs are
      capable of modulating mesoaccumbens DA pathway activity at post-synaptic level by
      specifically controlling DA signaling in the NAc core subregion. In keeping with
      the tight relationship between locomotor activity and NAc DA function, this
      interaction could participate in the inhibitory control of cocaine-induced
      locomotor activity. 

PMID- 24661381
TI  - Treatment of comminuted distal radius fractures by resurfacing prosthesis in
      elderly patients.
AB  - In elderly patients, distal radius fractures are often associated with
      osteoporotic bone. Under these conditions, anatomic resurfacing implants may
      provide satisfactory results in terms of range of motion, pain and function.
      Between July 2009 and January 2012, eight elderly patients were treated with the
      SOPHIATM implant at our hand surgery department. Inclusion criteria were isolated
      comminuted distal radius AO type C2 fractures in patients greater than 70 years
      of age. All patients were reviewed in February 2013 by an independent surgeon.
      Clinical, functional and radiographic assessments were performed. Mean follow-up
      was 25 months (range 17-36 months). Mean ROM was 45 degrees  (range 40-50 degrees
      ) in flexion and 44 degrees  (range 40-50 degrees ) in extension. Mean pronation
      supination range was 160 degrees . Mean grip strength was 18 kgf. Mean Quick DASH
      was 18.2/100 (range 6.82-29.55) and mean pain on VAS was 2.33 (range 0-4). X-rays
      did not reveal any implant loosening or ulnar translation of the carpus. Use of a
      wrist resurfacing implant led to rapid recovery of autonomy in elderly patients
      with comminuted distal radius fractures. It parallels the use of shoulder or
      elbow prostheses for complex joint fractures in the elderly.

PMID- 24661382
TI  - [Old pseudoarthrosis with large bone defect of the radius treated with the Watson
      Jones technique: a case report].
AB  - Large bone defects in the forearm pose a challenging reconstruction problem,
      especially when the condition has become chronic. The Watson-Jones technique is a
      relatively simple procedure that sacrifices pronation-supination, but allows the
      forearm to be used in everyday life. Here, we describe a unique case of one-bone
      forearm reconstruction for a patient who had been suffering from radius non-union
      for several years. This reconstruction technique provided the patient with
      acceptable function and appearance of the arm. 

PMID- 24661383
TI  - Comparing nurse managers and nurses' perceptions of nurses' self-leadership
      during capacity building.
AB  - AIMS: This paper compares the perceptions of nurse managers and nurses about self
      leadership of professional nurses while taking ownership of capacity building
      during unit management. BACKGROUND: The Nursing Strategy for South Africa states
      that the competency of nurses is dependent upon factors that lead to capacity
      building. METHOD: A quantitative design was followed by conducting a survey. The
      target population included nurse managers and professional nurses working at an
      academic public hospital in the Gauteng Province of South Africa. RESULTS: The
      findings indicate shortcomings in relation to advising professional nurses about
      self-direction while taking ownership of their daily pressures and stresses
      associated with unit management. CONCLUSION: Professional nurses should develop
      their confidence by focusing on their self-leadership strengths when managing a
      unit. IMPLICATIONS FOR NURSE MANAGERS: Recommendations are made to promote self
      leadership while taking ownership of nurses during capacity building of unit
      management.

PMID- 24661384
TI  - Diabetic neuropathy and Nd-YAG (1064 nm) laser for onychomycosis: be careful.

PMID- 24661385
TI  - Changes in the oral-health-related quality of life of Brazilian children after an
      educational preventive programme: an 1-month longitudinal evaluation.
AB  - OBJECTIVE: This 1-month longitudinal study assessed whether the oral status and
      the oral-health-related quality of life (OHRQoL) of children changed after four
      sessions of an educational preventive programme. STUDY POPULATION AND METHODS:
      Fifty Brazilian students (11-12 year old) were examined for signs and symptoms of
      gingivitis using the Community Periodontal Index and two questions about gingival
      bleeding. The OHRQoL was measured using the Brazilian Portuguese version of the
      Child Oral Impacts on Daily Performances (Child-OIDP). Higher scores indicated
      worse OHRQoL. The results were analysed using the Shapiro-Wilk, Chi-square,
      Wilcoxon signed-rank and Mann-Whitney tests. The magnitude of the mean change was
      calculated using the effect size. RESULTS: Twenty-four percentage of children had
      more than six sites with bleeding at follow-up compared with 58% at baseline.
      There was a significant decline in the intensity and extension of impacts at
      follow-up. A significant improvement in the clinical status and oral hygiene was
      observed for both transitional categories. There was a significant decline in the
      Child-OIDP scores of those reporting 'much improved'. A significant improvement
      in the global ratings of oral health was observed at follow-up. CONCLUSIONS: In
      the studied sample, an improvement occurred with respect to the severity of
      disease, intensity and extension of impacts and global ratings of oral health
      after 1-month follow-up. These results suggest that improving the global
      transition in health by enhancing coping and management skills while inducing
      slight changes in the clinical status and the specific aspects of health
      compromised by the disease is possible.

PMID- 24661387
TI  - Early discharge and readmission after colorectal resection.
AB  - BACKGROUND: Emphasis on the provision of high quality, cost-effective healthcare
      has meant increasing efforts at reducing postoperative length of stay while
      reducing 30-d readmission rates. The aim of this study was to identify factors
      associated with early discharge (ED) and to evaluate the effectof ED on
      readmission after colorectal resection. MATERIALS AND METHODS: We identified all
      inpatients aged >=18 y who underwent a colorectal resection in the American
      College of Surgeons National Surgical Quality Improvement Program Participant Use
      File, 2011. ED was defined as a length of stay <=25th percentile by procedure
      (rectal resection, open colectomy, and laparoscopic colectomy). Multivariate
      logistic regression was used to identify factors significantly associated with ED
      and readmission. A subset analysis was performed by procedure type. RESULTS: Of
      28,532 patients, 2171 (7%) underwent rectal resection, 14,976 (52%) underwent
      open colectomy, and 11,385 (40%) underwent laparoscopic colectomy with an ED on
      or before postoperative days 5, 5, and 3, respectively. The overall cohort
      included patients with a mean age of 61 y. A total of 52% were women and 37% were
      colorectal cancer patients. Age >65 y, recent steroid use, simultaneous ostomy
      creation, nonelective surgery, need for reoperation, and a postoperative
      occurrence before discharge were significantly associated with a reduced
      likelihood of ED. The overall rate of readmission was 12%. Patients who were
      discharged early were significantly less likely to be readmitted (odds ratio,
      0.77; 95% confidence interval, 0.70-0.84). CONCLUSIONS: In the appropriate
      patient population, ED after colorectal surgery may be implemented without any
      adverse effect on readmission rates.

PMID- 24661388
TI  - "The mothers have eaten unripe grapes and the children's teeth are set on edge":
      the potential inter-generational effects of the Holocaust on chronic morbidity in
      Holocaust survivors' offspring.
AB  - Modern epidemiology has evolved in the last decades from the simplified "cause
      effect" paradigm to a multi-factorial framework of causality. The concept of
      "Fetal Origin of Adult Diseases" (FOAD) is a good example: it suggests that
      preconception circumstances and fetal exposures as well as infancy and early
      childhood experiences may eventually change an individual's susceptibility to
      adult morbidity through fetal programming and epigenetic changes. The FOAD
      concept was supported, between others, by well-designed cohort studies carried
      out on non-Jewish World War II (WWII) survivors, exposed to hunger during the War
      years. However, data on late physical morbidity of Jewish WWII survivors are
      still scarce.The current paper presents some cohorts addressing the FOAD
      hypothesis in relation to the long-term impact of early exposures to hunger and
      their main results. It stresses the need for the establishing of a similar cohort
      in Israel, in order to study the long-term effects of the Holocaust on the health
      of Holocaust child survivors and on that of the "second" and "third" generations.
      A framework for such a cohort in Israel is also proposed.Establishing a cohort of
      this character in Israel should be a national priority and policy. First, taking
      special care of Holocaust survivors is a somewhat neglected national obligation.
      Second, if the population of Holocaust survivors and their offspring is indeed a
      high risk group for late chronic morbidity, higher awareness may lead to better
      primary prevention and to tailored secondary prevention programs. Third, the
      population at stack is unique and its contribution to the consolidation of the
      FOAD theory and its translational applications may be of foremost importance, in
      the global and national sense. 

PMID- 24661389
TI  - A bias-free two-alternative forced choice procedure to examine intersensory
      illusions applied to the ventriloquist effect by flashes and averted eye-gazes.
AB  - We compared with a new psychophysical method whether flashes and averted eye
      gazes of a cartoon face induce a ventriloquist illusion (an illusory shift of the
      apparent location of a sound by a visual distracter). With standard
      psychophysical procedures that measure a direct ventriloquist effect and a
      ventriloquist aftereffect, we found in human subjects that both types of stimuli
      induced an illusory shift of sound location. These traditional methods, though,
      are probably contaminated by response strategies. We therefore developed a new
      two-alternative forced choice procedure that allows measuring the strength of an
      intersensory illusion in a bias-free way. With this new procedure we found that
      only flashes, but not averted eye-gazes, induced an illusory shift in sound
      location. This difference between flashes and eye-gazes was validated in an EEG
      study in which again only flashes illusorily shifted the apparent location of a
      sound thereby evoking a mismatch negativity response. These results are important
      because they highlight that commonly used measures of multisensory illusions are
      contaminated while there is an easy yet stringent way to measure the strength of
      an illusion in a bias-free way. 

PMID- 24661390
TI  - Randomized trial of 'intelligent' autotitrating ventilation versus standard
      pressure support non-invasive ventilation: impact on adherence and physiological
      outcomes.
AB  - BACKGROUND AND OBJECTIVE: Effective non-invasive ventilation (NIV) therapy is
      dependent on optimal ventilator settings to maximize clinical benefit and patient
      tolerance. Intelligent volume-assured pressure support (iVAPS) is a hybrid mode
      of servoventilation, providing constant automatic adjustment of pressure support
      (PS) to achieve a target ventilation determined by the patient's requirements. In
      a randomized crossover trial, we tested the hypothesis that iVAPS, with automated
      selection of ventilator settings, was non-inferior to standard PS ventilation,
      with settings determined by an experienced health-care professional, for
      controlling nocturnal hypoventilation in patients naive to NIV. METHODS: Eighteen
      patients referred to a ventilator clinic with chronic obstructive or restrictive
      lung disease and newly diagnosed nocturnal hypoventilation (10 male, median
      (interquartile range): age 54(41-61) years, mean daytime PaO2 9.25(8.59-10.31)
      kPa, -PaCO2 6.38(5.93-6.65) kPa were randomized to iVAPS and standard PS.
      Polysomnography with transcutaneous CO2 monitoring was performed at baseline and
      1 month after each treatment period. Nightly hours of therapy were recorded by
      the ventilator. RESULTS: iVAPS delivered a lower median PS compared with standard
      PS (8.3(5.6-10.4) vs 10.0(9.0-11.4) cmH2 O; P = 0.001) for the same ventilatory
      outcome (mean overnight: SpO2 96(95-98) vs 96(93-97)%; P = 0.13 and PtcCO2
      6.5(5.8-6.8) vs 6.2(5.8-6.9); P = 0.54). There was no difference in outcome
      between ventilator modes for spirometry, respiratory muscle strength, sleep
      quality, arousals or O2 desaturation index. Adherence was greater with iVAPS
      (5:40(4:42-6:49) vs 4:20(2:27-6:17) hh:mm/night; P = 0.004). CONCLUSIONS: iVAPS
      servoventilation with automation of ventilation settings is as effective as PS
      ventilation initiated by a skilled health-care professional in controlling
      nocturnal hypoventilation and produced better overnight adherence in patients
      naive to NIV.

PMID- 24661391
TI  - Executive function and appetitive processes in the self-control of alcohol use:
      the moderational role of drinking restraint.
AB  - BACKGROUND: Dual process models characterize hazardous drinking as a function of
      appetitive processes and executive processes that enable self-control. Although
      central to a number of models (e.g., Hofmann et al., 2009a,b), little empirical
      research has examined how drinking restraint may influence the effects of these
      processes on alcohol use. The current study examined whether drinking restraint
      influenced the predictive value of appetitive responses to alcohol cues and
      executive functioning on typical drinking behavior. It was hypothesized that the
      interaction between appetitive responses and executive functioning would only be
      observed among those who had stronger drinking restraint goals. METHODS: Sixty
      nine hazardous drinking young adults (ages 21-30) completed the Trail Making Test
      and then were exposed to the sight and smell of an alcoholic beverage that they
      anticipated they would consume. Urge and anticipated stimulant effects of alcohol
      (A-BAES) were measured following the exposure. RESULTS: The interaction between
      Trails B and each of the appetitive response ratings (i.e., urge rating and A
      BAES) was predictive of drinking behavior (TLFB) only among those high in
      drinking restraint. CONCLUSIONS: These findings highlight the importance of
      incorporating the role of motivational constructs such as restraint goals in
      current dual process models of alcohol-related self-control.

PMID- 24661392
TI  - Characteristics of people who initiate injection drug use later in life.
AB  - BACKGROUND: Studies report that among people who inject drugs (PWID),
      approximately 1 in 7 initiated injection during their thirties or later (referred
      to hereafter as "late initiates"). However, little is known about individuals who
      are late initiates. This study aims to describe characteristics of late initiates
      to drug injection and to examine how they differ from people who initiated drug
      injection prior to the age of 30 ("typical initiates"). METHODS: We recruited 696
      active PWID in Los Angeles and San Francisco, California between 2011 and 2013,
      using targeted sampling and street outreach methods. Participants completed
      personal interviews that covered items on demographics, drug use history and
      practices, injection initiation episode, HIV injection- and sex-related risk,
      health care utilization among others. We used bivariate and multivariate analyses
      to examine factors associated being a late initiate. RESULTS: In our sample, 19%
      of participants who were 30 years or older were classified as late initiates. In
      multivariate analysis controlling for city, late initiates had higher odds of
      being female and African American, having been in treatment prior to initiation,
      initiating illicit drug use at an older age, and being assisted into injection by
      someone of the same age or younger. Late initiates had lower odds of frequent
      recent injection, and having a bipolar disorder diagnosis. CONCLUSION: Late
      initiates comprise a significant proportion of active PWIDs. More study on the
      health consequences of late initiation are needed as are interventions to prevent
      transition to drug injection among at-risk populations.

PMID- 24661393
TI  - CD14+ CD16+ monocytes rather than CD14+ CD51/61+ monocytes are a potential
      cytological marker of circulating osteoclast precursors in multiple myeloma. A
      preliminary study.
AB  - INTRODUCTION: Osteolytic bone destruction is a major clinical problem in multiple
      myeloma patients. Osteoclasts can differentiate in vitro from bone marrow
      resident monocyte progenitors, such as common monocyte progenitors, as well as
      circulating monocytes. Various types of monocytes, including osteoclast
      precursors, appear to circulate systemically. METHODS: We investigated the
      possibility of demonstrating, by in vitro differentiation and flow cytometry, a
      circulating osteoclast precursor population in multiple myeloma (MM) patients by
      studying the distribution of CD14(+/++) CD11b(+) CD51/61(+) and CD14(+/++)
      CD16(+/-) populations. RESULTS: Under short-term in vitro osteoclastic
      differentiation conditions, almost all CD14 monocytes acquired CD51/61 and CD16
      expression. Flow cytometry studies failed to demonstrate a statistically
      significant increase in circulating CD14(+/++) CD11b(+) CD51/61(+) populations in
      20 MM patients with osteolytic lesions. However, the minor circulating CD14(+/++)
      CD16(+) fraction was significantly increased in MM patients compared with healthy
      volunteers (109.3 +/- 63.1/mm(3) vs. 65.3 +/- 34.9/mm(3) ; P = 0.005), but with
      no correlation with markers of tumour burden. The CD14(+/++) CD16(+) to
      CD14(+/++) CD16(-) ratio was higher in MM patients. CONCLUSION: The circulating
      CD14(+/++) CD11b(+) CD51/61(+) fraction was not correlated with bone lesions in
      MM patients. However, CD14(+/++) CD16(+) monocytes may be a candidate marker. A
      larger study must be conducted to confirm these promising results for the
      diagnosis and follow-up of MM patients.

PMID- 24661394
TI  - Religious faith in coping with terminal cancer: what is the nursing experience?
AB  - This qualitative study describes nurses' reports on the role played by religious
      faith in the care of patients with terminal cancer. Using Gadamer's philosophical
      hermeneutics and C. Roy's adaptation model as a base, in-depth interviews were
      carried out with 23 nurses who had cared for patients with terminal cancer for at
      least 6 months. Three main themes emerged when a Gadamerian-based hermeneutic
      research method was applied: faith facilitates the coping process in cases of
      terminal cancer, faith hinders the coping process in cases of terminal cancer and
      terminal illness impacts faith. The lack of univocal results indicates that the
      role of faith in coping with death is essentially practical, individualised and
      changeable. The nurse-patient relationship can help to determine the spiritual
      needs of cancer patients at the end of life. This source of knowledge held by the
      nurse, together with the rest of the multidisciplinary team, can help to improve
      end-of-life care. 

PMID- 24661395
TI  - Matching patients to an intervention for back pain: classifying patients using a
      latent class approach.
AB  - RATIONALE, AIMS AND OBJECTIVES: Classification of patients with back pain in
      order to inform treatments is a long-standing aim in medicine. We used latent
      class analysis (LCA) to classify patients with low back pain and investigate
      whether different classes responded differently to a cognitive behavioural
      intervention. The objective was to provide additional guidance on the use of
      cognitive behavioural therapy to both patients and clinicians. METHOD: We used
      data from 407 participants from the full study population of 701 with complete
      data at baseline for the variables the intervention was designed to affect and
      complete data at 12 months for important outcomes. Patients were classified using
      LCA, and a link between class membership and outcome was investigated. For
      comparison, the latent class partition was compared with a commonly used
      classification system called Subgroups for Targeted Treatment (STarT). RESULTS:
      Of the relatively parsimonious models tested for association between class
      membership and outcome, an association was only found with one model which had
      three classes. For the trial participants who received the intervention, there
      was an association between class membership and outcome, but not for those who
      did not receive the intervention. However, we were unable to detect an effect on
      outcome from interaction between class membership and the intervention. The
      results from the comparative classification system were similar. CONCLUSION: We
      were able to classify the trial participants based on psychosocial baseline
      scores relevant to the intervention. An association between class membership and
      outcome was identified for those people receiving the intervention, but not those
      in the control group. However, we were not able to identify outcome associations
      for individual classes and so predict outcome in order to aid clinical decision
      making. For this cohort of patients, the STarT system was as successful, but not
      superior.

PMID- 24661396
TI  - Cultivating social justice learning & leadership skills: a timely endeavor for
      undergraduate student nurses.

PMID- 24661397
TI  - Causative organisms of post-traumatic endophthalmitis: a 20-year retrospective
      study.
AB  - BACKGROUND: A wide range of organisms that enter the eye following ocular trauma
      can cause endophthalmitis. This study was to investigate the spectrum of
      pathogens and antibiotic susceptibility of bacterial isolates from a large cohort
      of post-traumatic endophthalmitis cases. METHODS: A retrospective study of 912
      post-traumatic endophthalmitis patients treated at a tertiary eye-care center in
      China was performed. The associations between risk factors and the most common
      isolated organisms were investigated by Chi square Test. The percent
      susceptibilities for the first 10 years (1990-1999) and the second 10 years (2000
      2009) were compared by Chi square test. p < 0.05 was considered statistically
      significant. RESULTS: Three-hundred-forty-seven (38.1%) cases of endophthalmitis
      were culture-positive, and 11 (3.2%) showed mixed infections (Gram-negative
      bacilli and fungi), yielding a total of 358 microbial pathogens. Culture proven
      organisms included 150 (41.9%) Gram-positive cocci, 104 (29.1%) Gram-negative
      bacilli, 44 (12.3%) Gram-positive bacilli, and 60 (16.8%) fungi. The coagulase
      negative staphylococcal (CNS) species S. epidermidis (21.8%) and S. saprophyticus
      (12.0%) were the predominant pathogens, followed by Bacillus subtilis (8.7%),
      Pseudomonas aeruginosa (7.8%), and Escherichia coli (6.4%). Delayed repair over
      24 h (p < 0.001) and metallic injury (p < 0.01) were significantly associated
      with positive culture of CNS. The most frequent fungal species were Aspergillus
      (26/60), followed by yeast-like fungi (18/60). P. aeruginosa was relatively
      sensitive to ciprofloxacin (83.3%), cefoperazone (75%), tobramycin (75%),
      cefuroxime (75%), and ceftazidime (75%) during the second decade. Multi-drug
      resistance was observed in the predominant Gram-negative bacteria. CONCLUSION: We
      identified a broad spectrum of microbes causing post-traumatic endophthalmitis,
      with Gram-positive cocci the most frequently identified causative organism,
      followed by Bacillus species, fungi, and mixed infections. CNS infection was
      statistically associated with delayed repair and metallic injury. Variation in
      antibiotic susceptibility was observed among isolated bacteria and between
      different periods. Ciprofloxacin and ceftazidime in the first and second decades
      of the study, respectively, showed the highest activity against bacterial post
      traumatic endophthalmitis. For infections caused by P. aeruginosa, a combination
      therapy of ciprofloxacin, tobramycin, and one of the cephalosporins might provide
      optimal coverage according to data from the second decade.

PMID- 24661398
TI  - Reconciliation of international administrative coding systems for comparison of
      colorectal surgery outcome.
AB  - AIM: Significant variation in colorectal surgery outcomes exists between
      different countries. Better understanding of the sources of variable outcomes
      using administrative data requires alignment of differing clinical coding
      systems. We aimed to map similar diagnoses and procedures across administrative
      coding systems used in different countries. METHOD: Administrative data were
      collected in a central database as part of the Global Comparators (GC) Project.
      In order to unify these data, a systematic translation of diagnostic and
      procedural codes was undertaken. Codes for colorectal diagnoses, resections,
      operative complications and reoperative interventions were mapped across the
      respective national healthcare administrative coding systems. Discharge data from
      January 2006 to June 2011 for patients who had undergone colorectal surgical
      resections were analysed to generate risk-adjusted models for mortality, length
      of stay, readmissions and reoperations. RESULTS: In all, 52 544 case records were
      collated from 31 institutions in five countries. Mapping of all the coding
      systems was achieved so that diagnosis and procedures from the participant
      countries could be compared. Using the aligned coding systems to develop risk
      adjusted models, the 30-day mortality rate for colorectal surgery was 3.95% (95%
      CI 0.86-7.54), the 30-day readmission rate was 11.05% (5.67-17.61), the 28-day
      reoperation rate was 6.13% (3.68-9.66) and the mean length of stay was 14 (7.65
      46.76) days. CONCLUSION: The linkage of international hospital administrative
      data that we developed enabled comparison of documented surgical outcomes between
      countries. This methodology may facilitate international benchmarking.

PMID- 24661399
TI  - Cystic artery pseudoaneurysm presenting as a complication of laparoscopic
      cholecystectomy treated with percutaneous thrombin injection.
AB  - A 45-year-old woman status post laparoscopic cholecystectomy 3years ago presented
      with upper gastrointestinal bleeding. Endoscopy revealed hemobilia. Computed
      tomographic abdomen demonstrated a 2-cm aneurysm in the gall bladder fossa,
      consistent with a pseudoaneurysm. Initially, transcatheter coil embolization was
      attempted but recanalization of the aneurysm with recurrent bleeding in 2 days
      ensued. The aneurysm was then accessed percutaneously under ultrasound guidance
      and thrombin was injected into the aneurysm with subsequent complete thrombosis
      of the aneurysm and cessation of bleeding. 

PMID- 24661400
TI  - Association of dementia with early rehospitalization among Medicare
      beneficiaries.
AB  - Preventable hospital readmissions have been recognized as indicators of hospital
      quality, a source of increased healthcare expenditures, and a burden for
      patients, families, and caregivers. Despite growth of initiatives targeting risk
      factors associated with potentially avoidable hospital readmissions, the impact
      of dementia on the likelihood of rehospitalization is poorly characterized.
      Therefore, the primary objective of this retrospective cohort study was to
      investigate whether dementia was an independent predictor of 30-day readmissions.
      Administrative claims data for all admissions to Rhode Island hospitals in 2009
      was utilized to identify hospitalizations of Medicare fee-for-service
      beneficiaries with a diagnosis of Alzheimer's Disease or other dementias.
      Demographics, measures of comorbid disease burden, and other potential
      confounders were extracted from the data and the odds of 30-day readmission to
      any United States hospital was calculated from conditional logistic regression
      models. From a sample of 25,839 hospitalizations, there were 3908 index
      admissions of Medicare beneficiaries who fulfilled the study criteria for a
      dementia diagnosis. Nearly 20% of admissions (n=5133) were followed by a
      readmission within thirty days. Hospitalizations of beneficiaries with a dementia
      diagnosis were more likely to be followed by a readmission within thirty days
      (adjusted odds ratio (AOR) 1.18; 95% CI, 1.08, 1.29), compared to
      hospitalizations of those of without dementia. Controlling for discharge site of
      care did not attenuate the association (AOR 1.21; 95% CI, 1.10, 1.33). 

PMID- 24661401
TI  - Cigarette smoking prevalence in US counties: 1996-2012.
AB  - BACKGROUND: Cigarette smoking is a leading risk factor for morbidity and
      premature mortality in the United States, yet information about smoking
      prevalence and trends is not routinely available below the state level, impeding
      local-level action. METHODS: We used data on 4.7 million adults age 18 and older
      from the Behavioral Risk Factor Surveillance System (BRFSS) from 1996 to 2012. We
      derived cigarette smoking status from self-reported data in the BRFSS and applied
      validated small area estimation methods to generate estimates of current total
      cigarette smoking prevalence and current daily cigarette smoking prevalence for
      3,127 counties and county equivalents annually from 1996 to 2012. We applied a
      novel method to correct for bias resulting from the exclusion of the wireless
      only population in the BRFSS prior to 2011. RESULTS: Total cigarette smoking
      prevalence varies dramatically between counties, even within states, ranging from
      9.9% to 41.5% for males and from 5.8% to 40.8% for females in 2012. Counties in
      the South, particularly in Kentucky, Tennessee, and West Virginia, as well as
      those with large Native American populations, have the highest rates of total
      cigarette smoking, while counties in Utah and other Western states have the
      lowest. Overall, total cigarette smoking prevalence declined between 1996 and
      2012 with a median decline across counties of 0.9% per year for males and 0.6%
      per year for females, and rates of decline for males and females in some counties
      exceeded 3% per year. Statistically significant declines were concentrated in a
      relatively small number of counties, however, and more counties saw statistically
      significant declines in male cigarette smoking prevalence (39.8% of counties)
      than in female cigarette smoking prevalence (16.2%). Rates of decline varied by
      income level: counties in the top quintile in terms of income experienced
      noticeably faster declines than those in the bottom quintile. CONCLUSIONS: County
      level estimates of cigarette smoking prevalence provide a unique opportunity to
      assess where prevalence remains high and where progress has been slow. These
      estimates provide the data needed to better develop and implement strategies at a
      local and at a state level to further reduce the burden imposed by cigarette
      smoking.

PMID- 24661402
TI  - Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in
      rats with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Stem cell transplantation is a promising method for the treatment of
      chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs)
      have clinical potential for lung repair/regeneration. However, the rates of
      engraftment and differentiation are generally low following MSC therapy for lung
      injury. In previous studies, we constructed a pulmonary surfactant-associated
      protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in
      alveolar epithelial type II (AT II) cells and vacated the AT II cell niche. We
      hypothesized that this system would increase the rates of MSC engraftment and
      repair in COPD rats. METHODS: The MSC engraftment rate and morphometric changes
      in lung tissue in vivo were investigated by in situ hybridization, hematoxylin
      and eosin staining, Masson's trichrome staining, immunohistochemistry, and real
      time PCR. The expression of hypoxia inducible factor (HIF-1alpha) and stromal
      cell-derived factor-1 (SDF-1), and relationship between HIF-1alpha and SDF-1 in a
      hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme
      linked immunosorbent assay. RESULTS: rAAV-SPA-TK transfection increased the
      recruitment of MSCs but induced pulmonary fibrosis in COPD rats. HIF-1alpha and
      SDF-1 expression were enhanced after rAAV-SPA-TK transfection. Hypoxia increased
      the expression of HIF-1alpha and SDF-1 in the hypoxic cell model, and SDF-1
      expression was augmented by HIF-1alpha under hypoxic conditions. CONCLUSIONS:
      Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung
      in COPD rats. MSCs play an important role in lung repair and promote collagen
      fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA
      TK, which involves HIF-1alpha and SDF-1 signaling.

PMID- 24661403
TI  - Cerebral infarction 3 weeks after intravenous immunoglobulin for Miller Fisher
      syndrome: a case report.
AB  - INTRODUCTION: Intravenous immunoglobulin is considered generally safe and is used
      widely as proven, and sometimes empiric, treatment for an expanding list of
      autoimmune diseases. Thromboembolic complications following intravenous
      immunoglobulin therapy are rare and there have been only five previous reports of
      stroke occurring within 2 to 10 days of infusion. This is the first report of
      cerebral infarction occurring after a longer latency of 3 weeks following
      intravenous immunoglobulin therapy in a patient presenting with Miller Fisher
      syndrome. CASE PRESENTATION: A previously well, 44-year-old Sri Lankan man
      progressively developed ophthalmoplegia, facial paralysis, ataxia and areflexia
      with neurophysiological and cerebrospinal fluid evidence consistent with the
      Miller Fisher syndrome. He made an unremarkable recovery with intravenous
      immunoglobulin therapy (0.4 g/kg/day for 5 days, total 180 g), but developed a
      cerebral infarct with haemorrhagic transformation 25 days later. He was noted to
      have a low blood pressure. Extensive investigations ruled out vasculopathic,
      embolic, thrombophilic and inflammatory aetiologies. Circulating intravenous
      immunoglobulins combined with a low blood pressure was considered the most
      probable cause of his stroke. CONCLUSIONS: Cerebral infarction following
      intravenous immunoglobulin is thought to be secondary to hyperviscosity,
      thromboemboli, vasculitis, or cerebral vasospasm and reported to occur after a
      short latency when the immunoglobulin load is highest. Even though the
      immunoglobulin load is halved by 3 weeks, our case suggests that that the
      predisposition to thromboembolism persists over a longer period and may result in
      vascular complications if synergised with other vascular risk factors. It is
      recommended that intravenous immunoglobulin be infused at a rate of not less than
      8 hours per day and that factors predisposing to thromboembolism such as
      dehydration, immobilisation and low blood pressure be avoided for the duration of
      at least two half-lives of immunoglobulin (6 weeks).

PMID- 24661404
TI  - Efficacy of antifungal PACT in an in vitro model of onychomycosis.
AB  - BACKGROUND: The difficulty of antifungal substances to penetrate keratin and slow
      nail growth limit the efficacy of topical therapy in onychomycosis. One promising
      alternative is photodynamic antimicrobial chemotherapy, or PACT: an irradiated
      photosensitizer creates singlet oxygen molecules which destroy pathogens without
      damaging human cells. OBJECTIVE: As PACT has demonstrated strong antifungal
      capabilities, we wanted to investigate its efficacy in an in vitro model of
      onychomycosis. METHODS: PACT was tested in a microdilution assay, in an in vitro
      onychomycosis model as well as in a patient. RESULTS: PACT inhibited fungal
      growth in the microdilution assay with no colonies of T. rubrum detectable.
      Fungal growth was also inhibited in an onychomycosis model, after 30 min of LED
      irradiation. Subsequently, a patient with distolateral onychomycosis was treated
      on three consecutive days and showed significant and durable improvement of nail
      morphology 6 months after. CONCLUSION: PACT appears to be an effective treatment
      of onychomycosis in vitro. The promising results need to be validated by clinical
      trials.  

PMID- 24661405
TI  - The prevalence of airway obstruction among Japanese HIV-positive male patients
      compared with general population; a case-control study of single center analysis.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have suggested that human
      immunodeficiency virus (HIV) infection and/or the airway colonization of
      Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction,
      such as chronic obstructive pulmonary disease (COPD). This study was aimed to
      evaluate the relationship between HIV infection, airway colonization of Pcj and
      airway obstruction in Japanese male patients. METHODS: Case-control study of 49
      HIV-positive and 257 HIV-negative men were enrolled in this study. Airway
      obstruction was determined by spirometry. Cigarette smoking was determined by a
      self report. Laboratory data were obtained from medical records. Among HIV
      positive patients, the airway colonization of Pcj was evaluated by induced sputum
      using the real time polymerase chain reaction method. RESULTS: Forty-eight out of
      49 (97.9%) HIV-positive patients received antiretroviral therapy, and their
      median CD4 cell counts were 491/MUL (79-935). The prevalence of airway
      obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects
      and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control
      group, HIV-positive patients were significantly younger (median age 44 vs 40, p =
      0.019). After adjusting for age, pack-years of smoking, HIV infection was an
      independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p =
      0.006). None of patient was detected the airway colonization of Pcj. CONCLUSIONS:
      HIV infection was an independent risk factor for airway obstruction regardless of
      airway colonization of Pcj. Health-care providers should be aware of the
      increased likelihood of airway obstruction among HIV-positive patients.

PMID- 24661406
TI  - Diagnosis and classification of non-alcoholic fatty liver disease and non
      alcoholic steatohepatitis: Current concepts and remaining challenges.
AB  - The high prevalence of non-alcoholic fatty liver disease (NAFLD) has made the
      condition an important public health issue. Two clinical entities are
      manifestations of NAFLD, namely, non-alcoholic fatty liver (NAFL) and non
      alcoholic steatohepatitis (NASH). The former tends to be benign and non
      progressive while the latter can progress to cirrhosis, which in rare cases gives
      rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a
      history of no or limited daily alcohol intake (<20 g for women and <30 g for
      men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii)
      exclusion of other liver diseases. NAFL is defined histologically by the presence
      of bland, primarily macrovesicular, hepatocellular fatty change, while NASH
      features fatty change with inflammation and evidence of hepatocyte injury, such
      as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus,
      the diagnosis of NAFL/NASH rests on clinicopathological criteria; it always
      requires both clinical and biopsy-based information. NAFLD could be both the
      result and the cause of metabolic syndrome, with a vicious cycle operating
      between these conditions. Remaining challenges are: (i) the lack of a clear
      threshold alcohol intake for defining "non-alcoholic"; (ii) a lacking consensus
      for the classification of fatty liver disease; and (iii) absence of a
      histological definition of NASH, which currently remains the gold standard for
      the diagnosis. Further challenges include the overlap of the criteria for NAFLD
      and alcoholic liver disease as many obese individuals also consume considerable
      volumes of alcohol. 

PMID- 24661407
TI  - Histochemical visualization of ROS and antioxidant response to viral infections
      of vegetable crops grown in Azerbaijan.
AB  - Extremes of environmental conditions, such as biotic stresses, strongly affect
      plant growth and development and may adversely affect photosynthetic process.
      Virus infection is especially problematic in crops, because unlike other
      diseases, its impact cannot be reduced by phytosanitary treatments. The vegetable
      crops (Solanum lycopersicum L, Cucurbita melo L., Cucumis sativus L., Piper
      longum L., Solanum melongena L., Vicia faba L.) showing virus-like symptoms were
      collected from fields located in the main crop production provinces of
      Azerbaijan. Infection of the plants were confirmed by Enzyme-linked immunosorbent
      assay using commercial kits for the following viruses: Tomato yellow leaf curl
      virus, Tomato mosaic virus, Tomato chlorosis virus, Melon necrotic spot virus and
      Cucumber mosaic virus, Bean common mosaic virus and Bean yellow mosaic virus.
      Generation sites of superoxide and hydrogen peroxide radicals and activities of
      enzymes involved in the detoxification of reactive oxygen species (catalase,
      glutathione reductase, ascorbate peroxidase, guaiacol peroxidase and superoxide
      dismutase) were examined in uninfected leaves and in leaves infected with
      viruses. High accumulation of superoxide and hydrogen peroxide radicals was
      visualized in infected leaves as a purple discoloration of nitro blue tetrazolium
      and 3,3'-diaminobenzidine tetrahydrochloride. It was found that the activities of
      APX and CAT significantly increased in all infected samples compared with non
      infected ones. Dynamics of GR and Cu/Zn-SOD activities differed from those of CAT
      and APX, and slightly increased in stressed samples. Electrophoretic mobility
      profiling of APX, GPX and CAT isoenzymes was also studied. 

PMID- 24661408
TI  - Diagnostic value of the soluble triggering receptor expressed on myeloid cells-1
      in lower respiratory tract infections: a meta-analysis.
AB  - The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a
      promising diagnostic marker for many types of infections. A bivariate meta
      analysis was performed to evaluate its diagnostic value for lower respiratory
      tract infections (LRTI). We searched PubMed, Cochrane Library and Web of Science
      (from January 1966 to August 2013) for all trials assessing diagnostic value of
      sTREM-1 for LRTI. The pooled sensitivity, specificity, positive likelihood
      ratio(PLR), negative likelihood ratio(NLR), diagnostic odds ratio (DOR), the area
      under summary receiver operator characteristic (SROC) curve and the Q* were
      calculated. Thirteen studies with 1138 patients were included in our meta
      analysis. The pooled sensitivity and specificity of sTREM-1 for diagnosis of LRTI
      was 0.84 and 0.77. The PLR, NLR and DOR were 3.6, 0.21 and 17. The area under
      SROC curve was 0.88 and the Q* was 0.82. The univariate meta-regression analysis
      demonstrated that the assay method for sTREM-1 significantly affected sensitivity
      for LRTI. The Q* of sTREM-1 for diagnosis of community-acquired LRTI was 0.82,
      and the area under SROC curve was 0.88. The Q* of sTREM-1 in diagnosis of
      hospital-acquired LRTI was 0.83, and the area under SROC curve was 0.90. The Q*
      of sTREM-1 for distinguishing culture-positive LRTI from culture-negative
      diseases was 0.79, and the area under SROC curve was 0.86. Current evidence
      suggests that sTREM-1 is an accurate marker of LRTI. The overall diagnostic value
      of sTREM-1 for LRTI, community-acquired LRTI and hospital-acquired LRTI is
      similar.

PMID- 24661409
TI  - Regulation and pharmacological blockade of sodium-potassium ATPase: a novel
      pathway to neuropathy.
AB  - Inflammation causes upregulation of NaV1.7 sodium channels in the associated
      dorsal root ganglia (DRG). The resultant increase in sodium influx must be
      countered to maintain osmotic homeostasis. The primary mechanism to pump sodium
      out of neurons is Na(+), K(+)-ATPase. To test whether there is a compensatory
      upregulation of Na(+), K(+)-ATPase after inflammation, rats received an injection
      of complete Freund's adjuvant (CFA) into one hindpaw and saline into the
      contralateral hindpaw. Three days later, L4-L6 DRGs were extracted and analyzed
      using gel electrophoresis and immunohistochemistry. Immunoreactivity for both the
      alpha-1 and alpha-3 subunits were increased in DRG associated with CFA-treatment,
      compared to saline-treatment. To test whether dysregulation of Na(+), K(+)-ATPase
      may cause cell death after inflammation, we produced a pharmacological blockade
      with ouabain (10mg/kg, s.c.) three days after CFA injection and paws were
      stimulated or not. Twenty-four hours later, DRG were removed and stained with
      cresyl violet. Greater cell death was seen in DRG from ouabain-treated animals on
      the CFA treated side than the saline-treated side. Paw stimulation doubled this
      difference. Control DRG showed little neuronal death. These results are evidence
      that regulation of Na(+), K(+)-ATPase during major inflammatory disease states is
      critical for homeostatic protection of primary afferent neurons. 

PMID- 24661410
TI  - Genotype-phenotype correlation in a cohort of paroxysmal kinesigenic dyskinesia
      cases.
AB  - BACKGROUND: Recently, PRRT2 gene mutations have been identified as a causative
      factor of paroxysmal kinesigenic dyskinesia (PKD). However, evidence is still
      lacking with respect to the genotype to phenotype correlation in PKD patients.
      METHODS: We recruited a cohort of PKD patients with or without PRRT2 mutations
      for the study, and followed them for 6 months to observe the response to
      carbamazepine treatment. RESULTS: Thirty-four participants were included in this
      study; 16 patients were positive for a hot-spot p.R217Pfs 8 heterozygous PRRT2
      gene mutation, while the other 18 patients were negative for PRRT2 gene
      mutations. PRRT2 mutations were found to be associated with a younger age of
      onset, bilateral presence and a higher frequency of attacks. Furthermore, the
      follow-up study revealed that p.R217Pfs 8-positive patients showed dramatic
      improvement with complete abolition of dyskinetic episodes with carbamazepine
      treatment, while only 7 of the 18 patients without PRRT2 mutations showed a
      response to the antiepileptic drug. CONCLUSIONS: Our study indicated that
      positivity for PRRT2 mutation is a predictor of younger age of onset and more
      frequent of attacks in PKD patients. Interestingly, the presence of PRRT2
      mutations also predicted a good response to carbamazepine therapy, especially at
      low dose. Therefore, genetic testing shows potential clinical significance for
      guiding the choice of medication for individual PKD cases.

PMID- 24661411
TI  - The socio-economic impact of chronic pancreatitis: a systematic review.
AB  - RATIONALE, AIMS AND OBJECTIVES: Chronic pancreatitis (CP) is a progressive
      inflammatory disorder with pain being the most frequent symptom. It is associated
      with loss of function, pancreatogenic diabetes and digestive enzyme deficiency.
      The impact of local complications and loss of pancreatic function results in
      unknown and unreported costs. This study attempts to identify both the direct and
      indirect costs associated with CP. METHODS: A MEDLINE literature review was
      performed for all relevant articles relating to any aspect of direct and indirect
      costs as a result of CP. RESULTS: In the UK, there are 12,000 admissions per
      annum of patients with CP at an estimated cost of L55.8 million. The costs for
      loss of pancreatic function are estimated at L45-90 million and $75.1 million for
      endocrine and exocrine function, respectively. Chronic pain contributes $638
      million per year in costs. The protracted course of CP and paucity of monetary
      data make quantifying direct and indirect costs difficult. An estimate of direct
      and indirect costs is at L285.3 million per year. This equates to L79,000 per
      person per year. CONCLUSIONS: Patients with CP consume a disproportionately high
      volume of resources.

PMID- 24661412
TI  - Changes in foot volume, body composition, and hydration status in male and female
      24-hour ultra-mountain bikers.
AB  - BACKGROUND: The effects of running and cycling on changes in hydration status and
      body composition during a 24-hour race have been described previously, but data
      for 24-hour ultra-mountain bikers are missing. The present study investigated
      changes in foot volume, body composition, and hydration status in male and female
      24-hour ultra-mountain bikers. METHODS: We compared in 49 (37 men and 12 women)
      24-hour ultra-mountain bikers (ultra-MTBers) changes (Delta) in body mass (BM).
      Fat mass (FM), percent body fat (%BF) and skeletal muscle mass (SM) were
      estimated using anthropometric methods. Changes in total body water (TBW),
      extracellular fluid (ECF) and intracellular fluid (ICF) were determined using
      bioelectrical impedance and changes in foot volume using plethysmography.
      Haematocrit, plasma [Na+], plasma urea, plasma osmolality, urine urea, urine
      specific gravity and urine osmolality were measured in a subgroup of 25 ultra
      MTBers (16 men and 9 women). RESULTS: In male 24-hour ultra-MTBers, BM (P <
      0.001), FM (P < 0.001), %BF (P < 0.001) and ECF (P < 0.05) decreased whereas SM
      and TBW did not change (P > 0.05). A significant correlation was found between
      post-race BM and post-race FM (r = 0.63, P < 0.001). In female ultra-MTBers, BM
      (P < 0.05), %BF (P < 0.05) and FM (P < 0.001) decreased, whereas SM, ECF and TBW
      remained stable (P > 0.05). Absolute ranking in the race was related to Delta%BM
      (P < 0.001) and Delta%FM in men (P < 0.001) and to Delta%BM (P < 0.05) in women.
      In male ultra-MTBers, increased post-race plasma urea (P < 0.001) was negatively
      related to absolute ranking in the race, Delta%BM, post-race FM and Delta%ECF (P
      < 0.05). Foot volume remained stable in both sexes (P > 0.05). CONCLUSIONS: Male
      and female 24-hour ultra-MTBers experienced a significant loss in BM and FM,
      whereas SM remained stable. Body weight changes and increases in plasma urea do
      not reflect a change in body hydration status. No oedema of the lower limbs
      occurred.

PMID- 24661413
TI  - Morbidity due to acute lower respiratory infection in children with birth
      defects: a total population-based linked data study.
AB  - BACKGROUND: Acute lower respiratory infections (ALRIs) are leading causes of
      hospitalisation in children. Birth defects occur in 5% of live births in Western
      Australia (WA). The association between birth defects and ALRI hospitalisation is
      unknown. METHODS: We conducted a retrospective cohort study of 245,249 singleton
      births in WA (1996-2005). Population-based hospitalisation data were linked to
      the WA Register of Developmental Anomalies to investigate ALRI hospitalisations
      in children with and without birth defects. We used negative binomial regression
      to estimate associations between birth defects and number of ALRI
      hospitalisations before age 2 years, adjusting for known risk factors. RESULTS:
      Overall, 9% of non-Aboriginal children and 37% of Aboriginal children with birth
      defects had at least one ALRI admission before age 2 years. Aboriginal children
      (IRR 2.3, 95% CI: 1.9-2.8) and non-Aboriginal children (IRR 2.0, 95% CI: 1.8-2.2)
      with birth defects had higher rates of hospitalisation for an ALRI than children
      with no birth defects. Rates of ALRI hospitalisation varied by type of defect but
      were increased for all major birth defects categories, the highest rate being for
      children with Down syndrome (IRR 8.0, 95% CI: 5.6-11.5). The rate of ALRI
      hospitalisation was 3 times greater in children with multiple birth defects than
      in those with isolated defects. CONCLUSIONS: Children with birth defects
      experience higher rates of hospitalisation for ALRIs before age 2 years than
      children with no birth defects. Optimal vaccination coverage and
      immunoprophylaxis for specific categories of birth defects would assist in
      reducing hospitalisation rates for ALRI.

PMID- 24661415
TI  - The confounding effects of tumour heterogeneity and cellular plasticity on
      personalized surgical management of colorectal cancer.

PMID- 24661414
TI  - Discovering new bioactive molecules from microbial sources.
AB  - There is an increased need for new drug leads to treat diseases in humans,
      animals and plants. A dramatic example is represented by the need for novel and
      more effective antibiotics to combat multidrug-resistant microbial pathogens.
      Natural products represent a major source of approved drugs and still play an
      important role in supplying chemical diversity, despite a decreased interest by
      large pharmaceutical companies. Novel approaches must be implemented to decrease
      the chances of rediscovering the tens of thousands of known natural products. In
      this review, we present an overview of natural product screening, focusing
      particularly on microbial products. Different approaches can be implemented to
      increase the probability of finding new bioactive molecules. We thus present the
      rationale and selected examples of the use of hypersensitive assays; of accessing
      unexplored microorganisms, including the metagenome; and of genome mining. We
      then focus our attention on the technology platform that we are currently using,
      consisting of approximately 70,000 microbial strains, mostly actinomycetes and
      filamentous fungi, and discuss about high-quality screening in the search for
      bioactive molecules. Finally, two case studies are discussed, including the spark
      that arose interest in the compound: in the case of orthoformimycin, the novel
      mechanism of action predicted a novel structural class; in the case of NAI-112,
      structural similarity pointed out to a possible in vivo activity. Both
      predictions were then experimentally confirmed.

PMID- 24661416
TI  - The structure of the human vaginal stratum corneum and its role in immune
      defense.
AB  - The superficial layers of the human vaginal epithelium, which form an interface
      between host and environment, are comprised of dead flattened cells that have
      undergone a terminal cell differentiation program called cornification. This
      entails extrusion of nuclei and intercellular organelles, and the depletion of
      functional DNA and RNA precluding the synthesis of new proteins. As a
      consequence, the terminally differentiated cells do not maintain robust
      intercellular junctions and have a diminished capacity to actively respond to
      microbial exposure, yet the vaginal stratum corneum (SC) mounts an effective
      defense against invasive microbial infections. The vaginal SC in reproductive
      aged women is comprised of loosely connected glycogen-filled cells, which are
      permeable to bacterial and viral microbes as well as molecular and cellular
      mediators of immune defense. We propose here that the vaginal SC provides a
      unique microenvironment that maintains vaginal health by fostering endogenous
      lactobacilli and retaining critical mediators of acquired and innate immunity. A
      better understanding of the molecular and physicochemical properties of the
      vaginal SC could promote the design of more effective topical drugs and
      microbicides. 

PMID- 24661417
TI  - Ewe characteristics associated with neonatal loss in Norwegian sheep.
AB  - A case-control study was conducted to identify ewe characteristics that affect
      the risk of a ewe losing at least one lamb during the first 5 days post lambing.
      Data were from a national sheep registry, and only ewes that lambed in the spring
      of 2010 belonging to flocks that reported disease events were included. Ewes
      registered with abortion or stillbirth were excluded. Cases (n=4850) and controls
      (n=85,354) from 1153 flocks were studied using logistic regression models,
      accounting for within flock correlation. The odds of losing at least one lamb
      increased substantially when litter size exceeded two. For example, in 3-year-old
      ewes, the odds were 6 times greater for those with 3 lambs than for those with 1
      lamb. However, the effect of litter size depended on the age of the ewe; for
      example for ewes giving birth to triplet lambs, the odds of losing at least one
      lamb were 2.7 times greater in 1-year-old ewes than in 3-year-old ewes. Dystocia
      was associated with increased risk of losing at least one lamb, but the effect
      varied by litter size. In ewes with single lambs, the odds of lamb loss were 5
      times greater in those that experienced dystocia than in those that did not,
      while within subgroups of ewes with twins, triplets or >3 lambs, the
      corresponding odds ratio (OR) of losing one or more lambs was 2.2, 1.5 and 1.3,
      respectively. Compared with ewes of the Norwegian White breed, ewes of old
      Norwegian breeds were less likely to lose lambs (OR=0.8). We also examined the
      effects of several diseases experienced by the ewe during pregnancy or shortly
      postpartum on the risk of subsequent neonatal lamb loss. Significantly increased
      risk was found for ewes with abdominal hernia (OR=2.5) and for ewes treated for
      moderate to severe clinical mastitis (OR=1.6) when compared with ewes without
      these disorders. In conclusion, our large study population allowed for a detailed
      analysis of the combined effect of important ewe factors that affected survival
      of their lambs in the early neonatal period. 

PMID- 24661418
TI  - JNK suppresses pulmonary fibroblast elastogenesis during alveolar development.
AB  - BACKGROUND: The formation of discrete elastin bands at the tips of secondary
      alveolar septa is important for normal alveolar development, but the mechanisms
      regulating the lung elastogenic program are incompletely understood. JNK suppress
      elastin synthesis in the aorta and is important in a host of developmental
      processes. We sought to determine whether JNK suppresses pulmonary fibroblast
      elastogenesis during lung development. METHODS: Alveolar size, elastin content,
      and mRNA of elastin-associated genes were quantitated in wild type and JNK
      deficient mouse lungs, and expression profiles were validated in primary lung
      fibroblasts. Tropoelastin protein was quantitated by Western blot. Changes in
      lung JNK activity throughout development were quantitated, and pJNK was localized
      by confocal imaging and lineage tracing. RESULTS: By morphometry, alveolar
      diameters were increased by 7% and lung elastin content increased 2-fold in JNK
      deficient mouse lungs compared to wild type. By Western blot, tropoelastin
      protein was increased 5-fold in JNK-deficient lungs. Postnatal day 14 (PND14)
      lung JNK activity was 11-fold higher and pJNK:JNK ratio 6-fold higher compared to
      PN 8 week lung. Lung tropoelastin, emilin-1, fibrillin-1, fibulin-5, and lysyl
      oxidase mRNAs inversely correlated with lung JNK activity during alveolar
      development. Phosphorylated JNK localized to pulmonary lipofibroblasts. PND14 JNK
      deficient mouse lungs contained 7-fold more tropoelastin, 2,000-fold more emilin
      1, 800-fold more fibrillin-1, and 60-fold more fibulin-5 than PND14 wild type
      lungs. Primarily lung fibroblasts from wild type and JNK-deficient mice showed
      similar differences in elastogenic mRNAs. CONCLUSIONS: JNK suppresses fibroblast
      elastogenesis during the alveolar stage of lung development.

PMID- 24661421
TI  - Bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted
      patient: a case report.
AB  - INTRODUCTION: Endogenous Fusarium endophthalmitis is a rare disease predominantly
      described in immunocompromised patients often due to leukemia. We report a case
      of bilateral endogenous Fusarium solani endophthalmitis in a liver-transplanted
      patient. CASE PRESENTATION: A 56-year-old Danish Caucasian woman who had
      undergone two liver transplantations, developed endogenous endophthalmitis of her
      left eye 10 days after the second liver transplantation. Despite continuous
      therapy, enucleation of her left eye was eventually necessary; at this point
      funduscopic examination of her right eye disclosed a white inflammatory plaque at
      the macula consistent with a fungal infection. Microbiological analysis of
      vitreous fluid from her enucleated left eye revealed Fusarium solani, and light
      microscopy of her enucleated eye was consistent with Fusarium panophthalmitis
      with massive ingrowth of the fungi in all areas containing basement membrane
      collagen. Voriconazole was injected intravitreally in her right eye, and
      intravenous voriconazole was initiated. No subsequent growth in the inflammatory
      plaque was observed. She died 6 weeks after the endogenous endophthalmitis was
      diagnosed. CONCLUSIONS: This is the first report of endogenous Fusarium solani
      endophthalmitis in a liver-transplanted patient. Ophthalmologists and physicians
      dealing with liver transplantation should be aware of the potential for
      postoperative endophthalmitis due to rare microorganisms, such as Fusarium
      solani.

PMID- 24661420
TI  - Dermatoscopy of flat pigmented facial lesions.
AB  - BACKGROUND: The diagnosis of flat pigmented lesions on the face is challenging
      because of the morphologic overlap of biologically different lesions and the
      unknown significance of dermatoscopic patterns. OBJECTIVE: To better characterize
      dermatoscopic patterns of various types of flat pigmented facial lesions and to
      analyse their significance by calculating their relative risks and diagnostic
      values. METHODS: We prospectively analysed dermatoscopic images of 240 flat
      pigmented facial skin lesions collected consecutively from 195 patients (41.5%
      females, mean age: 61 +/- 14 years) between 2007 and March 2012 in a primary skin
      cancer practice situated in Queensland, Australia. RESULTS: Histopathologically
      114 (47.5%) lesions were malignant (24 lentigo maligna, 21 basal cell carcinomas
      and 69 pigmented actinic keratoses). Compared with all other patterns the
      positive predictive value for lentigo maligna was highest for a pattern of
      circles (31.3%, 95% CI: 11.1-58.6%). A pattern of clods was associated with basal
      cell carcinoma. If grey structures were present the relative risk for malignancy
      was 2.2 (95%CI: 1.4-3.4). The best clues to differentiate pigmented actinic
      keratosis from other lesions were the presence of scale (positive predictive
      value: 72.2%, specificity: 94.2%), white circles (positive predictive value:
      68.8%, specificity: 94.2%) and a sharply demarcated border (positive predictive
      value: 44.2%, specificity: 86.0%). CONCLUSIONS: In flat lesions a pattern of
      circles bears the highest risk for facial melanoma but other patterns do not
      exclude it. Scale, white circles and a sharply demarcated border are clues to
      pigmented actinic keratoses. The presence of grey colour is a clue to malignancy
      regardless of pattern.

PMID- 24661419
TI  - The role of glutamate in the morphological and physiological development of
      dendritic spines.
AB  - Dendritic spines form the postsynaptic half of the synapse but how they form
      during CNS development remains uncertain, as are the factors that promote their
      morphological and physiological maturation. One hypothesis posits that filopodia,
      long motile dendritic processes that are present prior to spine formation, are
      the precursors to spines. Another hypothesis posits that they form directly from
      the dendritic shaft. We used microphotolysis of caged glutamate to stimulate
      individual dendritic processes in young hippocampal slice cultures while
      recording their morphological and physiological responses. We observed that brief
      trains of stimuli delivered to immature processes triggered morphological changes
      within minutes that resulted, in about half of experiments, in a more mature,
      spine-like appearance such as decreased spine neck length and increased spine
      head width. We also observed that glutamate-induced inward currents elicited from
      immature processes were mostly or entirely mediated by NMDARs, whereas responses
      in those processes with a more mature morphology, regardless of actual
      developmental age, were mediated by both AMPARs and NMDARs. Consistent with this
      observation, glutamate-induced morphological changes were largely, but not
      entirely, prevented by blocking NMDARs. Our observations thus favor a model in
      which filopodia in the developing nervous system sense and respond to release of
      glutamate from developing axons, resulting in physiological and morphological
      maturation. 

PMID- 24661422
TI  - Outcome of microvascular free flaps in a high-volume training centre.
AB  - PURPOSE: Microvascular free tissue transfer allows major ablative defects
      following oncologic surgical and traumatic reasons to be reliably reconstructed
      in the head and neck region. A retrospective analysis of the microvascular flap
      procedures which were performed within one year in a high volume training centre
      was performed. PATIENTS AND METHODS: The microvascular free flap procedures of
      the year 2011 were reviewed and followed up until the 31st December 2012. The
      type and indication of the reconstructive procedure, operation time, operating
      team, experience and level of training of the surgeons involved, postoperative
      IMC (intermediate care unit) and/or ICU (intensive care unit) time, inpatient
      time, flap revisions, further postoperative complications, preoperative and
      postoperative radiation of the patients, the placement of dental implants were
      studied. RESULTS: From 1st of January 2011 to 31st of December, 2011, the data of
      101 patients with 103 microvascular free flap procedures were analysed of which
      72% (84 flaps) were harvested by residents. The patients ranged in age from 14 to
      89 years (mean age 59 years, 71 males and 40 females). The mean operation time
      was 591 min with the longest operation times for scapular flaps (744 min) and the
      shortest operation times for ALT flaps (455 min). Mean inpatient time was 34.2
      days with a minimal time for the fibular flaps of 27.2 days and a maximum of 45.7
      days for the latissimus dorsi flaps. 24 flaps (23.3%) in total had to be revised
      with bleeding being the main cause of immediate revisions (41.7% of all
      revisions). 5 flaps (4.85% of all flaps) were lost despite a revision procedure
      meaning a successful revision rate in 79.2% of all revisions. CONCLUSION:
      Microvascular reconstruction procedures are safe and should be considered as
      standard procedures for reconstruction of large defects especially in high volume
      training centres. Intensive flap monitoring and early revisions maximize the flap
      outcome.

PMID- 24661423
TI  - Nosocomial infections within the first month of solid organ transplantation.
AB  - Infections remain a common complication of solid organ transplantation. Early
      postoperative infections remain a significant cause of morbidity and mortality in
      solid organ transplant (SOT) recipients. Although significant effort has been
      made to understand the epidemiology and risk factors for early nosocomial
      infections in other surgical populations, data in SOT recipients are limited. A
      literature review was performed to summarize the current understanding of
      pneumonia, urinary tract infection, surgical-site infection, bloodstream
      infection, and Clostridium difficult colitis, occurring within the first 30 days
      after transplantation.

PMID- 24661424
TI  - Diagnostic utility of VEGF mRNA and SP1 mRNA expression in bronchial cells of
      patients with lung cancer.
AB  - BACKGROUND AND OBJECTIVE: Bronchial brushing is important for cytological
      diagnosis of lung carcinoma; however, cytological evaluation alone remains
      relatively insensitive. The aim of this study was to assess the diagnostic
      utility of vascular endothelial growth factor (VEGF) messenger ribonucleic acid
      (mRNA) and specificity protein 1 (SP1) mRNA in bronchial brushings in patients
      with or without lung cancer. METHODS: VEGF mRNA and SP1 mRNA were measured in
      liquid-based cells from bronchial brushings in patients with verified lung cancer
      (n = 93) and with benign lung disease that included tuberculosis (n = 51). This
      was done using the reverse-transcription polymerase chain reaction. RESULTS: Both
      VEGF mRNA and SP1 mRNA were significantly more likely to be expressed in the
      cancer group than in the control (benign) group, whatever their cell type. It was
      also more often found in the tuberculosis group than in the inflammation group (P
      < 0.01). In the cancer group, VEGF mRNA was significantly correlated with SP1
      mRNA (P < 0.01). Of the 36 false negative cytology results, 30 gave positive
      results for VEGF mRNA and 34 for SP1 mRNA. The four false positive VEGF results
      were all diagnosed as tuberculosis. VEGF mRNA gave the highest diagnostic
      performance with serial use: sensitivity 89.2% and accuracy 90.3%. This was
      significantly better than cytology (P < 0.01). CONCLUSIONS: Detection of VEGF
      mRNA and SP1 mRNA in bronchial brushing cells may be used as an ancillary tool to
      cytological diagnosis for detection of early-stage lung cancer. It may also help
      distinguish tuberculosis from other causes of lung inflammation.

PMID- 24661425
TI  - Performance of aseptic technique during neuraxial analgesia for labor before and
      after the publication of international guidelines on aseptic technique.
AB  - BACKGROUND: Aseptic technique and handwashing have been shown to be important
      factors in perioperative bacterial transmission, however compliance often remains
      low despite guidelines and educational programs. Infectious complications of
      neuraxial (epidural and spinal) anesthesia are severe but fortunately rare. We
      conducted a survey to assess aseptic technique practices for neuraxial anesthesia
      in Israel before and after publication of international guidelines (which focused
      on handwashing, jewelry/watch removal and the wearing of a mask and cap).
      METHODS: The sampling frame was the general anesthesiology workforce in hospitals
      selected from each of the four medical faculties in Israel. Data was collected
      anonymously over one week in each hospital in two periods: April 2006 and
      September 2009. Most anesthesiologists received the questionnaires at
      departmental staff meetings and filled them out during these meetings;
      additionally, a local investigator approached anesthesiologists not present at
      these staff meetings individually. Primary endpoint questions were: handwashing,
      removal of wristwatch/jewelry, wearing mask, wearing hat/cap, wearing sterile
      gown; answering options were: "always", "usually", "rarely" or "never". Primary
      endpoint for analysis: respondents who both always wash their hands and always
      wear a mask ("handwash-mask composite") - "always" versus "any other response".
      We used logistic regression to perform the analysis. Time (2006, 2009) and
      hospital were included in the analysis as fixed effects. RESULTS: 135/160 (in
      2006) and 127/164 (in 2009) anesthesiologists responded to the surveys; response
      rate 84% and 77% respectively. Respondents constituted 23% of the national
      anesthesiologist workforce. The main outcome "handwash-mask composite" was
      significantly increased after guideline publication (33% vs 58%; p = 0.0003). In
      addition, significant increases were seen for handwashing (37% vs 63%; p =
      0.0004), wearing of mask (61% vs 78%; p < 0.0001), hat/cap (53% vs 76%; p =
      0.0011) and wearing sterile gown (32% vs 51%; p < 0.0001). An apparent
      improvement in aseptic technique from 2006 to 2009 is noted across all hospitals
      and all physician groups. CONCLUSION: Self-reported aseptic technique by Israeli
      anesthesiologists improved in the survey conducted after the publication of
      international guidelines. Although the before-after study design cannot prove a
      cause-effect relationship, it does show an association between the publication of
      international guidelines and significant improvement in self-reported aseptic
      technique.

PMID- 24661426
TI  - Low potency and limited efficacy of antiepileptic drugs in the mouse 6 Hz corneal
      kindling model.
AB  - Corneal kindling is a useful alternative to electrically induced amygdala or
      hippocampal kindling, which requires advanced surgical and EEG techniques that
      may not be easily available in many laboratories. Therefore the first aim of this
      study was to evaluate whether repeated 6 Hz corneal stimulation in mice would
      lead to an increased and persistent seizure response as described for higher
      frequency (50/60 Hz) corneal kindling. Male NMRI mice stimulated twice daily
      (except weekends) for 3 s with 6 Hz electrical current at 44 mA displayed robust
      kindling development, i.e., a progressive increase in seizure severity. The
      majority of the animals (about 90%) developed a fully kindled state, defined as
      at least 10 consecutive stage 3-5 seizures within 5 weeks of corneal stimulation.
      Afterwards, the fully kindled state was maintained for at least 8 weeks with only
      two days of stimulations per week. Next, the protective efficacy of four
      mechanistically different antiepileptic drugs (AEDs; clonazepam, valproate,
      carbamazepine and levetiracetam) was assessed and compared between 6 Hz and 50 Hz
      fully kindled mice. All tested AEDs showed a relatively lower potency in the 6 Hz
      kindling model and a limited efficacy against partial seizures was observed with
      carbamazepine and levetiracetam. We can conclude that 6 Hz kindling may be more
      advantageous than the previously described 50/60 Hz corneal kindling models due
      to its robustness and persistence of the fully kindled state. Furthermore, the
      observed low potency and limited efficacy of AEDs in 6 Hz fully kindled mice
      suggest that this model could be a useful tool in the discovery of novel AEDs
      targeting treatment resistant epilepsy.

PMID- 24661427
TI  - Beyond the lesion: the epileptogenic networks around cavernous angiomas.
AB  - The relationship between epileptogenic lesions and the extension of
      epileptogenicity is a major challenge in presurgical evaluation of drug resistant
      epilepsies. In this study, we aimed at quantifying the epileptogenic properties
      of brain structures explored by depth electrodes in patients investigated by
      stereoelectroencephalography (SEEG) and suffering from focal drug-resistant
      epilepsy associated with cavernous angioma (CA). Epileptogenicity of the
      perilesional region and distant brain areas was calculated according to the
      "epileptogenicity index" (EI), a technique that allows mathematical
      quantification of rapid discharges at seizure onset taking into account the time
      at which the discharge occurs. Thirteen seizures from 6 patients were studied.
      Localization of the cavernoma was the frontal lobe (two cases), the temporal lobe
      (three cases) or the anterior insula (one case). Visual inspection of the ictal
      discharge showed that in the majority of cases (5/6) the perilesional region was
      either not involved or involved with other distant sites. Using EI
      quantification, complex patterns of epileptogenicity were observed in five
      patients. A large number of brain regions out of the lesional region disclosed
      higher values than the lesion site. Mean values in the perilesional region and in
      the extralesional sites were not significantly different (p=0.34). Complex
      organization of the epileptogenic zone may be found in drug-resistant CA
      associated epilepsy. Thus, this result should be borne in mind when patients with
      CA and drug resistant epilepsy are investigated. If there is a suspicion of a
      larger epileptogenic zone than the lesion, intra-cerebral exploration by SEEG may
      be required before surgery that may be guided by the definition of the EZ. 

PMID- 24661428
TI  - Temporal lobe epilepsy surgery modulates the activity of auditory pathway.
AB  - The purpose of this paper is to evaluate the effects of the anterior temporal
      lobectomy on the functional state of the auditory pathway in a group of drug
      resistant epileptic patients, linking the electrophysiological results to the
      resection magnitude. Twenty-seven patients with temporal lobe epilepsy and a
      matched control group were studied. Auditory brainstem and middle latency
      responses (ABR and MLR respectively) were carried out before and after 6, 12 and
      24 months surgical treatment. The volume and longitude of temporo-mesial resected
      structures were estimated on magnetic resonance images taken 6 months after
      surgery. Before the intervention the patients showed a significant delay of
      latency in waves III, V, Pa and Nb, with an increase in duration of I-V interval
      in comparison with healthy subjects (Mann-Whitney U-test, p<0.05). After
      resection, additional significant differences in waves I and Na latency were
      observed. Na and Pa waveforms showed a tendency to increase in amplitude, which
      became statistically significant 12 months after surgery for right hemisphere
      lobectomized patients in the midline electrode, and in Pa waveform for all
      patients in the temporal electrodes ipsilateral to resection (Wilcoxon test,
      p<0.05). In general, latency variations of MLR correlated with resection
      longitude, while changes in amplitude correlated with the volume of the resection
      in the middle temporal pole and amygdala (Pearson' correlation test, p<0.05). As
      a result, we assume that anterior temporal lobectomy provokes functional
      modifications into the auditory pathway, probably related to an indirect
      modulation of its activity by the temporo-mesial removed structures. 

PMID- 24661429
TI  - Immediate, early and late seizures after primary intracerebral hemorrhage.
AB  - BACKGROUND: Seizures after primary intracerebral hemorrhage (PICH) are
      significant and treatable complications, but the factors predicting immediate,
      early and late seizures are poorly known. We investigated characteristics and
      outcome with special reference to occurrence and timing of a first seizure among
      consecutive subjects with PICH. METHODS: A population-based study was conducted
      in Northern Ostrobothnia, Finland, in 1993-2008 that included all patients with a
      first-ever primary ICH without any prior diagnosis of epilepsy. Immediate (<24h
      after admission), early (1-14 days) and late (>2 weeks) seizures were considered
      separately. RESULTS: Out of a total of 935 ICH patients, 51 had immediate, 21
      early and 58 late seizures. The patients with seizures were significantly younger
      than the others and more often had a subcortical hematoma location (p<0.05).
      Lifestyle factors did not differ between the groups. The risk factors for
      immediate seizures in multivariable analysis were a low Glasgow coma scale score
      (GCS) on admission, subcortical location and age inversely (p<0.01). The only
      independent risk factor for early seizures was subcortical location (p<0.001),
      whereas subcortical location (p<0.001), age inversely (p<0.01) and hematoma
      evacuation (p<0.05) independently predicted late seizures. Immediate and early
      seizures predicted infectious complications (p<0.05). CONCLUSIONS: Patients with
      subcortical hematoma and of younger age are at risk for immediate seizures after
      primary ICH irrespective of hematoma size. Patients with immediate and early
      seizures more often had infectious complications. Surgery increases the risk of a
      late seizure after ICH.

PMID- 24661430
TI  - The enrichment behavior of natural radionuclides in pulverized oil shale-fired
      power plants.
AB  - The oil shale industry is the largest producer of NORM (Naturally Occurring
      Radioactive Material) waste in Estonia. Approximately 11-12 million tons of oil
      shale containing various amounts of natural radionuclides is burned annually in
      the Narva oil shale-fired power plants, which accounts for approximately 90% of
      Estonian electricity production. The radionuclide behavior characteristics change
      during the fuel combustion process, which redistributes the radionuclides between
      different ash fractions. Out of 24 operational boilers in the power plants, four
      use circulating fluidized bed (CFB) technology and twenty use pulverized fuel
      (PF) technology. Over the past decade, the PF boilers have been renovated, with
      the main objective to increase the efficiency of the filter systems. Between 2009
      and 2012, electrostatic precipitators (ESP) in four PF energy blocks were
      replaced with novel integrated desulphurization technology (NID) for the
      efficient removal of fly ash and SO2 from flue gases. Using gamma spectrometry,
      activity concentrations and enrichment factors for the (238)U ((238)U, (226)Ra,
      (210)Pb) and (232)Th ((232)Th, (228)Ra) family radionuclides as well as (40)K
      were measured and analyzed in different PF boiler ash fractions. The radionuclide
      activity concentrations in the ash samples increased from the furnace toward the
      back end of the flue gas duct. The highest values in different PF boiler ash
      fractions were in the last field of the ESP and in the NID ash, where
      radionuclide enrichment factors were up to 4.2 and 3.3, respectively. The
      acquired and analyzed data on radionuclide activity concentrations in different
      PF boiler ashes (operating with an ESP and a NID system) compared to CFB boiler
      ashes provides an indication that changes in the fuel (oil shale) composition and
      boiler working parameters, as well as technological enhancements in Estonian oil
      shale fired power plants, have had a combined effect on the distribution patterns
      of natural radionuclides in the oil shale combustion products. 

PMID- 24661431
TI  - Hierarchical mesoporous nickel cobaltite nanoneedle/carbon cloth arrays as
      superior flexible electrodes for supercapacitors.
AB  - Hierarchical mesoporous NiCo2O4 nanoneedle arrays on carbon cloth have been
      fabricated by a simple hydrothermal approach combined with a post-annealing
      treatment. Such unique array nanoarchitectures exhibit remarkable electrochemical
      performance with high capacitance and desirable cycle life at high rates. When
      evaluated as an electrode material for supercapacitors, the NiCo2O4 nanoneedle
      arrays supported on carbon cloth was able to deliver high specific capacitance of
      660 F g-1 at current densities of 2 A g-1 in 2 M KOH aqueous solution. In
      addition, the composite electrode shows excellent mechanical behavior and long
      term cyclic stability (91.8% capacitance retention after 3,000 cycles). The
      fabrication method presented here is facile, cost-effective, and scalable, which
      may open a new pathway for real device applications. 

PMID- 24661432
TI  - Public knowledge and perceptions of connected health.
AB  - RATIONALE, AIMS AND OBJECTIVES: This study aims to examine the public's knowledge
      and perceptions of connected health (CH). METHODS: A structured questionnaire was
      administered by face-to-face interview to an opportunistic sample of 1003 members
      of the public in 11 shopping centres across Northern Ireland (NI). Topics
      included public knowledge of CH, opinions about who should provide CH and views
      about the use of computers in health care. Multivariable analyses were conducted
      to assess respondents' willingness to use CH in the future. RESULTS: Sixty-seven
      per cent of respondents were female, 31% were less than 30 years old and 22% were
      over 60 years. Most respondents had never heard of CH (92%). Following a standard
      definition, the majority felt CH was a good idea (~90%) and that general
      practitioners were in the best position to provide CH; however, respondents were
      equivocal about reductions in health care professionals' workload and had some
      concerns about the ease of device use. Factors positively influencing willingness
      to use CH in the future included knowledge of someone who has a chronic disease,
      residence in NI since birth and less concern about the use of information
      technology (IT) in health care. Those over 60 years old or who felt threatened by
      the use of IT to store personal health information were less willing to use CH in
      the future. CONCLUSION: Increased public awareness and education about CH is
      required to alleviate concerns and increase the acceptability of this type of
      care.

PMID- 24661433
TI  - Gross placental morphology and foal serum biochemistry as predictors of foal
      health.
AB  - The aim of this study was to verify if changes in blood glucose, creatinine,
      urea, and fibrinogen concentrations evaluated at birth reflect gross placenta
      abnormalities, and are useful to identify foals that suffered from placental
      dysfunction. A total of 92 mares were included in the present study: 68 delivered
      healthy foals and they were included in group 1; 24 delivered sick foals and they
      were included in group 2. In group 2, foals' clinical diagnoses included
      perinatal asphyxia syndrome (PAS; n = 20) and prematurity and/or dysmaturity (n =
      4). The proportion of sick foals was greater when placental abnormalities were
      observed (chi(2) [1, n = 89] = 5.00; P = 0.025). Serum creatinine concentration
      at birth was higher in sick than in healthy foals (P = 0.003), and blood glucose
      concentrations at birth was smaller in sick than in healthy foals (P = 0.007). No
      difference was found in blood chemistry results between survivors and
      nonsurvivors of group 2. Serum creatinine concentration was higher in foals born
      from grossly abnormal than in foals born from grossly normal placenta (P =
      0.029), and it was higher in foals affected by PAS (311.17 MUmol/L) than in
      healthy foals (238.24 MUmol/L) (P = 0.004). In a clinical setting, serum
      creatinine and blood glucose concentrations should be evaluated at birth,
      particularly in foals born from grossly abnormal placenta. The association of
      clinical and laboratory data could be particularly important to promptly identify
      and treat foals with a higher risk to develop PAS.

PMID- 24661434
TI  - Serum insulin-like growth factor-I, iron, C-reactive protein, and serum amyloid A
      for prediction of outcome in dogs with pyometra.
AB  - Pyometra, accumulation of pus in the uterus, is a bacterial infection that
      frequently initiates systemic inflammation. The disease may have lethal
      consequences when the systemic effects are severe or complications occur. Markers
      for identifying high-risk patients and predicting outcome are therefore in high
      demand. The objective of this study was to measure serum concentrations of
      insulin-like growth factor-I (IGF-I), iron, C-reactive protein (CRP), and serum
      amyloid A (SAA) in bitches with pyometra and to explore the possible value of
      these variables for detection of increased morbidity. In total, 31 bitches were
      diagnosed with pyometra and destined for surgical treatment (ovariohysterectomy)
      and 17 healthy bitches were included in the study. Concentrations of IGF-I and
      iron were lower in the pyometra group (mean concentration 221.2 +/- 22.5 ng/mL
      and 16.9 +/- 1.6 MUmol/L, respectively) compared with the healthy control group
      (mean concentration 366.7 +/- 46.2 ng/mL and 38.1 +/- 2.7 MUmol/L, respectively).
      In contrast, concentrations of CRP and SAA were significantly higher in bitches
      with pyometra (mean concentrations 212.9 +/- 17.3 mg/L and 119.9 +/- 8.5 mg/L,
      respectively) compared with the control group (<5 mg/L and <10 mg/L,
      respectively). None of the explored variables were associated with morbidity as
      measured by duration of postoperative hospitalization. In conclusion, IGF-I and
      iron concentrations were decreased in pyometra, whereas SAA and CRP
      concentrations were increased in the disease. Although unspecific, measurement of
      these variables may be valuable as adjunctive markers for prognosis in cases of
      pyometra. 

PMID- 24661435
TI  - Optimized feline vitrectomy technique for therapeutic stem cell delivery to the
      inner retina.
AB  - OBJECTIVE: To describe an optimized surgical technique for feline vitrectomy
      which reduces bleeding and aids posterior gel clearance in order to facilitate
      stem cell delivery to the inner retina using cellular scaffolds. PROCEDURES:
      Three-port pars plana vitrectomies were performed in six-specific pathogen-free
      domestic cats using an optimized surgical technique to improve access and
      minimize severe intraoperative bleeding. RESULTS: The surgical procedure was
      successfully completed in all six animals. Lens sparing vitrectomy resulted in
      peripheral lens touch in one of three animals but without cataract formation.
      Transient bleeding from sclerotomies, which was readily controlled, was seen in
      two of the six animals. No cases of vitreous hemorrhage, severe postoperative
      inflammation, retinal detachment, or endophthalmitis were observed during
      postoperative follow-up. CONCLUSIONS: Three-port pars plana vitrectomy can be
      performed successfully in the cat in a safe and controlled manner when the
      appropriate precautions are taken to minimize the risk of developing
      intraoperative hemorrhage. This technique may facilitate the use of feline models
      of inner retinal degeneration for the development of stem cell transplantation
      techniques using cellular scaffolds.

PMID- 24661436
TI  - Prevalence of depression and its associated factors among patients attending
      primary care settings in the post-conflict Northern Province in Sri Lanka: a
      cross-sectional study.
AB  - BACKGROUND: In Sri Lanka, civilians in the Northern Province were affected by a
      long-term armed conflict that ended in 2009. This study aims to describe the
      prevalence of depression and its associated factors among adult patients
      attending primary care settings in the Northern Province in Sri Lanka. METHODS:
      We report data from a cross-sectional patient morbidity registry established in
      16 primary care facilities (12 Divisional Hospitals and 4 Primary Medical Care
      Units) in four districts of the Northern Province. The Patient Health
      Questionnaire-9 (PHQ-9) was used to assess depression among all patients aged >=
      18 years, between March and May 2013. A sample of 12,841 patient records was
      included in the analysis. A total score of >= 10 in the PHQ-9 was considered as
      major depression. Factors associated with major depression were tested using
      multivariable logistic regression analysis. RESULTS: The prevalence of major
      depression was 4.5% (95% CI: 4.1-4.9) and mild depression was 13.3% (95% CI: 12.7
      13.9). The major depression was significantly higher in females than males (5.1%
      vs. 3.6%) and among unpaid family workers (6.0%) than any other category who
      earned an income (varied between 1.2% and 3.2%). The prevalence was rising
      significantly with advancing age, and ranged from 0.3% in the youngest to 11.6%
      in the elderly.Multivariable regression analysis revealed that the females have a
      higher risk for major depression than males (OR = 1.4; 95% CI: 1.1-1.7). Older
      patients were more likely to be depressed than younger patients, OR (95% CI) were
      4.9 (1.9-12.5), 5.6 (2.2-14.0), 5.7 (2.3-14.2) and 4.7 (1.8-11.9) for the age
      groups 25-34, 35-49, 50-64, and >= 65 years respectively, in contrast to 18-24
      year group. Disability in walking (OR = 7.5; 95% CI: 5.8-9.8), cognition (OR =
      4.5; 95% CI: 3.6-5.6), self-care (OR = 2.6; 95% CI: 1.7-4.0), seeing (OR = 2.3;
      95% CI: 1.8-3.0), and hearing (OR = 2.0; 95% CI: 1.5-2.5) showed significant
      associations with depression. CONCLUSIONS: Depression is a common issue at
      primary care settings in a post-conflict population, and the elders, women and
      persons with disability are at a greater risk. Strengthening capacity of primary
      care facilities and community mental health services is necessary for early
      detection and management.

PMID- 24661437
TI  - Sitagliptin reduces the urine albumin-to-creatinine ratio in type 2 diabetes
      through decreasing both blood pressure and estimated glomerular filtration rate.
AB  - BACKGROUND: We investigated the change in the urine albumin-to-creatinine ratio
      (ACR) to examine the effect of sitagliptin on diabetic nephropathy. METHODS:
      Sitagliptin at a dose of 50 mg was administered to 247 outpatients with type 2
      diabetes. Data were collected on the patients' laboratory results (including the
      ACR), blood pressure, and body weight. Clinical data were compared before and
      after 3 months' administration of sitagliptin. RESULTS: The ACR changed from
      150.0 +/- 538.6 mg/gCre to 148.3 +/- 764.6 mg/gCre over 3 months. In the patients
      with micro- and macro-albuminuria, the ACR after 3 months significantly decreased
      compared with the baseline (P = 0.04 and P = 0.02, respectively). The subjects
      whose ACR decreased experienced significantly larger decreases over the 3-month
      period in blood pressure and estimated glomerular filtration rate (eGFR) than the
      other subjects. There was no significant correlation between change in ACR
      (DeltaACR) and change in hemoglobin A1c (DeltaHbA1c) during 3 months (r = 0.04, P
      = 0.59), but there was a significant correlation between change in DeltaACR and
      change in systolic blood pressure (r = 0.16, P = 0.03). Multiple regression
      analysis revealed that the significant predictors for DeltaACR were change in
      systolic blood pressure (beta = 0.21, P = 0.016) and change in eGFR (beta = 0.20,
      P = 0.024) over 3 months (r = 0.35, P = 0.04). CONCLUSIONS: Sitagliptin reduces
      the ACR through decreasing both blood pressure and eGFR, with no correlation with
      a decrease in HbA1c over a 3-month period. These results may reflect the direct
      action of sitagliptin on the kidneys.

PMID- 24661438
TI  - The barrier to HIV transmission provided by genital tract Lactobacillus
      colonization.
AB  - While resistance to HIV transmission is due to multiple mechanisms such as the
      epithelium, a lower genital tract microbiota dominated by Lactobacillus appears
      to play an important role. This article reviews selected recent research on
      genital tract microbiota in women including how microbiota impacts HIV resistance
      and factors affecting Lactobacillus colonization. 

PMID- 24661439
TI  - Transient protein-protein interface prediction: datasets, features, algorithms,
      and the RAD-T predictor.
AB  - BACKGROUND: Transient protein-protein interactions (PPIs), which underly most
      biological processes, are a prime target for therapeutic development. Immense
      progress has been made towards computational prediction of PPIs using methods
      such as protein docking and sequence analysis. However, docking generally
      requires high resolution structures of both of the binding partners and sequence
      analysis requires that a significant number of recurrent patterns exist for the
      identification of a potential binding site. Researchers have turned to machine
      learning to overcome some of the other methods' restrictions by generalising
      interface sites with sets of descriptive features. Best practices for dataset
      generation, features, and learning algorithms have not yet been identified or
      agreed upon, and an analysis of the overall efficacy of machine learning based
      PPI predictors is due, in order to highlight potential areas for improvement.
      RESULTS: The presence of unknown interaction sites as a result of limited
      knowledge about protein interactions in the testing set dramatically reduces
      prediction accuracy. Greater accuracy in labelling the data by enforcing higher
      interface site rates per domain resulted in an average 44% improvement across
      multiple machine learning algorithms. A set of 10 biologically unrelated proteins
      that were consistently predicted on with high accuracy emerged through our
      analysis. We identify seven features with the most predictive power over multiple
      datasets and machine learning algorithms. Through our analysis, we created a new
      predictor, RAD-T, that outperforms existing non-structurally specializing machine
      learning protein interface predictors, with an average 59% increase in MCC score
      on a dataset with a high number of interactions. CONCLUSION: Current methods of
      evaluating machine-learning based PPI predictors tend to undervalue their
      performance, which may be artificially decreased by the presence of un-identified
      interaction sites. Changes to predictors' training sets will be integral to the
      future progress of interface prediction by machine learning methods. We reveal
      the need for a larger test set of well studied proteins or domain-specific
      scoring algorithms to compensate for poor interaction site identification on
      proteins in general.

PMID- 24661440
TI  - Psychological distress and adjustment to disease in patients before and after
      radical prostatectomy. Results of a prospective multi-centre study.
AB  - The aim of this prospective multi-centre study was to evaluate the level of
      psychological distress (PD) and adjustment to disease in patients who underwent
      radical prostatectomy. Furthermore, the impact of urinary incontinence and
      erectile dysfunction on PD was assessed. Anxiety, depression and PD were
      evaluated using the Hospital Anxiety and Depression Scale in 329 prostate cancer
      patients before surgery as well as 3, 6 and 12 months after surgery. These
      results were compared with those of a male German general population reference
      group. Adjustment to disease was assessed using the Perceived Adjustment to
      Chronic Illness Scale. Patients reported low levels of PD at all points of
      assessment similar to population norms of age-matched German men. Persistent PD
      was seen in about 8% of the patients and 20% had PD at least two of the
      measurement points. Relevant predictors for PD after surgery were urinary
      symptoms and baseline PD. Adjustment to disease was highest before surgery and
      had significantly reduced at 3 and 6 months after surgery. In general, men are
      resilient to the experience of localised prostate cancer and adjust well
      psychologically after surgery. However, between 8% and 20% of patients could
      possibly benefit from mental health support. 

PMID- 24661441
TI  - Gnathostoma spinigerum in live Asian swamp eels (Monopterus spp.) from food
      markets and wild populations, United States.
AB  - In Southeast Asia, swamp eels (Synbranchidae: Monopterus spp.) are a common
      source of human gnathostomiasis, a foodborne zoonosis caused by advanced third
      stage larvae (AL3) of Gnathostoma spp. nematodes. Live Asian swamp eels are
      imported to US ethnic food markets, and wild populations exist in several states.
      To determine whether these eels are infected, we examined 47 eels from markets
      and 67 wild-caught specimens. Nematodes were identified by morphologic features
      and ribosomal intergenic transcribed spacer-2 gene sequencing. Thirteen (27.7%)
      M. cuchia eels from markets were infected with 36 live G. spinigerum AL3: 21
      (58.3%) in liver; 7 (19.4%) in muscle; 5 (13.8%) in gastrointestinal tract, and 3
      (8.3%) in kidneys. Three (4.5%) wild-caught M. albus eels were infected with 5 G.
      turgidum AL3 in muscle, and 1 G. lamothei AL3 was found in a kidney (both North
      American spp.). Imported live eels are a potential source of human
      gnathostomiasis in the United States. 

PMID- 24661442
TI  - Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood
      of veterans with posttraumatic stress disorder.
AB  - BACKGROUND: Enhanced glucocorticoid receptor (GR) sensitivity is present in
      people with posttraumatic stress disorder (PTSD), but the molecular mechanisms of
      GR sensitivity are not understood. Epigenetic factors have emerged as one
      potential mechanism that account for how trauma exposure leads to sustained PTSD
      symptoms given that PTSD develops in only a subset of trauma survivors. METHODS:
      Cytosine methylation of a relevant promoter of the GR gene (NR3C1-1F promoter)
      and three functional neuroendocrine markers of hypothalamic-pituitary-adrenal
      axis function were examined in a sample of 122 combat veterans. RESULTS: Lower
      NR3C1-1F promoter methylation in peripheral blood mononuclear cells (PBMCs) was
      observed in combat veterans with PTSD compared with combat-exposed veterans who
      did not develop PTSD. NR3C1-1F promoter methylation was also associated with
      three functional measures of glucocorticoid activity that have been associated
      with PTSD in combat veterans: PBMCs' lysozyme inhibition on the lysozyme
      suppression test, plasma cortisol decline on the low-dose (.50 mg) dexamethasone
      suppression test, and 24-hour urinary cortisol excretion. Finally, NR3C1-1F
      promoter methylation was inversely correlated with clinical markers and symptoms
      associated with PTSD. CONCLUSIONS: Alterations in NR3C1-1F promoter methylation
      may reflect enduring changes resulting from combat exposure that lead to
      functional neuroendocrine alterations. Because epigenetic measures are thought to
      reflect enduring effects of environmental exposures, they may be useful in
      distinguishing combat-exposed veterans who do or do not develop PTSD.

PMID- 24661443
TI  - Cutaneous spread of primary neuroendocrine breast carcinoma with apocrine
      differentiation.

PMID- 24661444
TI  - Participation and enjoyment of leisure activities in adolescents born at <= 29
      week gestation.
AB  - BACKGROUND AND OBJECTIVES: Motor, cognitive, social and behavioral problems have
      been found to persist in adolescents born extremely preterm. Leisure
      participation has been associated with health benefits; however, few studies have
      explored leisure participation in this population. The aim of this study was to
      describe leisure participation in adolescents born at <=29week gestation.
      Secondary aims were to identify potential differences in participation related to
      sex, age, motor competence, and cognitive ability, and between adolescents born
      preterm and their siblings born at term. METHODS: This cross-sectional study
      included 128 adolescents (mean age: 16.0years; 67 females) with a mean
      gestational age of 26.5weeks. All participants, as well as 22 siblings born at
      term, completed the Children's Assessment of Participation and Enjoyment.
      RESULTS: Participation levels were highest in social and recreational activities,
      and lowest in active-physical and skill-based activities. Boys participated in
      more active-physical activities (p=0.01) and more often (p<0.001) than girls,
      whereas girls had higher participation levels in social and self-improvement
      activities (p<0.05) than boys. Older adolescents engaged in more social
      activities (p=0.01) and more frequently (p=0.002) than younger adolescents.
      Overall, participants with poor motor and cognitive skills had lower
      participation levels in active-physical and social activities. Adolescents born
      preterm participated in fewer recreational activities compared to term-born
      siblings (p=0.013). CONCLUSIONS: Engagement in active-physical and skill-based
      leisure activities needs to be promoted in boys, and especially in girls with a
      history of prematurity. Activities should be adapted to sex and individual skill
      level in order to promote participation.

PMID- 24661445
TI  - Cardiovascular biomarkers pro-atrial natriuretic peptide and pro-endothelin-1 to
      monitor ductus arteriosus evolution in very preterm infants.
AB  - BACKGROUND: The diagnostic and prognostic appraisal of patent ductus arteriosus
      (PDA) in preterm infants is still debatable. AIMS: To compare plasma
      cardiovascular biomarkers with echocardiographic indices alongside ductus
      arteriosus (DA) evolution in very preterm infants within the first week of life.
      METHODS: Mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal
      pro-endothelin-1 (CT-proET-1) levels were prospectively measured on the second
      and sixth days of life (DOL) in 52 preterm infants born before 32weeks of
      gestation. Echocardiographic indices to define DA patency and significance were
      simultaneously obtained. Logistic regression and receiver operating
      characteristics (ROC) analyses were used to assess and quantify the biomarkers'
      diagnostic capacities. RESULTS: Thirty infants exhibited PDA on DOL 2; in 21 of
      these infants, DA was characterized as hemodynamically significant. Treatment
      failure after a first course of indomethacin was noted in 8 infants (DOL 6),
      whereas 7 participants underwent later surgical ligation. The diagnostic accuracy
      of cardiovascular biomarkers was moderate on DOL 2 but high on DOL 6. PDA was the
      only significant predictor of MR-proANP levels on DOL 6, independent of the
      effect of clinical confounders (regression coefficient 0.426, R(2) 0.60). Infants
      with MR-proANP >=850pmol/l on DOL 2 had 3.9-fold higher risk (95% CI 1.01 to
      14.5) of being diagnosed with significant DA, whereas infants with MR-proANP
      >=700pmol/l on DOL 6 had 7.1-fold higher risk (1.9 to 27.2) for pharmaceutical
      treatment failure. CONCLUSION: The cardiovascular plasma biomarker MR-proANP is a
      promising candidate for monitoring PDA evolution in very preterm infants.

PMID- 24661446
TI  - Executive function is associated with social competence in preschool-aged
      children born preterm or full term.
AB  - BACKGROUND: Executive function (EF), defined as higher-order cognitive processes
      used in planning and organizing actions and emotions, is often impaired in
      children born preterm. Few studies have assessed social competence, the processes
      and resources required to meet social demands and achieve social goals, in
      children born preterm. The relations between EF and social competence in preterm
      and full term preschoolers have not been well characterized. AIMS: To
      characterize social competence and assess the relationship between EF and social
      competence in preschool-aged children born preterm or full term. STUDY DESIGN:
      Cross-sectional study. SUBJECTS: Study subjects had a history of preterm birth
      (<=34weeks of gestation) and birth weight <2500g (n=70). Controls were born full
      term (>=37weeks) (n=79). OUTCOME MEASURES: Children completed a battery of EF
      tasks; a mean age-adjusted z-score for the battery was generated for each child.
      Parents rated child EF on one scale and child social competence on two
      standardized scales. RESULTS: Compared to full term children, preterm children
      showed a lower mean EF battery z-score, poorer parent-rated EF, and poorer scores
      on the two social competence scales. In hierarchical multiple regression models,
      EF battery z-score and parent-rated EF made independent contributions to both
      measures of social competence. Preterm birth explained additional variance for
      one measure of social competence. CONCLUSIONS: Standard assessment of EF skills
      and social competence in young preschool children, including children born
      preterm, may identify at-risk children for long-term social difficulties and may
      also provide targets for intervention.

PMID- 24661447
TI  - Typical sleep positions in pregnant women.
AB  - OBJECTIVE: Maternal supine posture in late pregnancy and labor is known to
      compromise maternal hemodynamics and subsequently affect the fetus. Recently,
      maternal supine sleep position during late pregnancy has been postulated to play
      a role in stillbirth. However, no objective data exist regarding how often
      pregnant women sleep supine. This study was therefore conducted to determine the
      proportion of pregnant women who spend time asleep in the supine position.
      METHODS: A secondary analysis of data from pregnant women who underwent home
      sleep studies. RESULTS: Of 51 pregnant women, mean gestational age 28.3+/
      6.9weeks, the vast majority of women (82.4%) spent some time sleeping in the
      supine position. The median proportion of overall time spent in the supine sleep
      position was 26.5% (90%CI 0.0-82.9%). CONCLUSION: Our data suggest that if supine
      position plays a role in stillbirth, most women may benefit from education
      regarding sleep position. PRACTICE IMPLICATIONS: Most pregnant women spend time
      asleep on their back. Given the known data on supine posture and maternal
      cardiovascular compromise together with emerging data on supine sleep position
      and stillbirth, it may be pertinent for healthcare providers to provide pregnant
      women with information about sleep position particularly during late pregnancy.

PMID- 24661448
TI  - Early exposure to maternal voice: effects on preterm infants development.
AB  - BACKGROUND: Preterm infants complete their development in Neonatal Intensive Care
      Unit being exposed to environmental stimuli that lead to the early maturation of
      the sensory systems. It is known that the fetus perceives sounds and reacts to
      them with movements since the 26th-28th week of gestational age. Maternal voice
      represents a source of sensory stimulation for the fetus. AIMS: To investigate
      the effect of the exposure to maternal voice, administered by bone conduction, on
      preterm infants autonomic and neurobehavioral development. STUDY DESIGN:
      Longitudinal, explorative, case control study. SUBJECTS: 71 preterm infants with
      birth weight <1500g, born adequate for gestational age OUTCOME MEASURES: vital
      and neurobehavioral parameters at term, neurofunctional assessment at 3 and
      6months of corrected age. RESULTS: Infants in the treatment group had lower heart
      rate values and a higher proportion of stable skin color at each study point as
      compared to the control group. The scores in the visual attention performance and
      in the quality of the general movements at term were better in the treatment
      group than in the control one. Neurofunctional assessment score at 3months of
      corrected age was higher in the treatment group whereas no difference between the
      two groups was detected at 6months of corrected age. CONCLUSIONS: Early exposure
      to maternal voice exerts a beneficial effect on preterm infants autonomic and
      neurobehavioral development.

PMID- 24661449
TI  - Role of laparoscopy and ultrasound in the management of "impalpable testis" in
      children.
AB  - BACKGROUND: Undescended testes is one of the most common congenital abnormalities
      in boys. In cases of impalpable testes, ultrasound is often used to find the
      testis, which frequently provides false-negative results. Recently, laparoscopy
      has become popular in the management of impalpable testes. METHODS: Retrospective
      study of all children with impalpable testes presenting for laparoscopy between
      August 2007 and July 2011 who had undergone ultrasound examinations without
      localizing the testes was conducted and the role of laparoscopy in diagnosing
      impalpable testes was evaluated. RESULTS: Twenty-three patients presented with
      impalpable testes for laparoscopy. All patients underwent ultrasound examinations
      in which the testes could not be identified. Of the 23 patients, Five patients
      were found to have palpable testes in the superficial inguinal pouch under
      anesthesia and proceeded to conventional open exploration during which the testes
      were brought into the scrotum. Eighteen patients were found to have impalpable
      testes in an evaluation under anesthesia (EUA) and proceeded to laparoscopy.
      Twelve patients were found to have intra-abdominal testes and underwent
      laparoscopic-assisted orchidopexy. Three patients underwent a two-stage Fowler
      Stephens procedure, and two patients with "vanishing" testes with the vas and
      atrophic vessels entering a closed internal ring proceeded to open exploration
      and orchidectomy for atrophic testes. In addition, a teenager with atrophic
      testes underwent laparoscopic orchidectomy. CONCLUSIONS: Laparoscopy is superior
      to ultrasound in the management of impalpable testes when high-resolution
      ultrasound is not available during the diagnostic process, with respect to both
      the sensitivity of localizing the testis and being more time and cost effective.

PMID- 24661450
TI  - Laparoendoscopic single-site (LESS) retroperitoneal partial adrenalectomy using a
      custom-made single-access platform and standard laparoscopic instruments:
      technical considerations and surgical outcomes.
AB  - BACKGROUND: We previously reported our initial experience with laparoendoscopic
      single-site (LESS) retroperitoneal partial adrenalectomy using a custom-made
      single-port device and conventional straight laparoscopic instruments. METHODS:
      Between December 2010 and February 2012, LESS retroperitoneal partial
      adrenalectomies were performed in 11 patients. Six patients had aldosterone
      producing adenomas (APAs) and five patients had nonfunctioning tumors. A single
      port access was created with an Alexis wound retractor (Applied Medical, Rancho
      Santa Margarita, CA, USA) through an incision of 2-3 cm beneath the tip of the
      12th rib. All procedures were performed with straight laparoscopic instruments.
      RESULTS: All LESS procedures were successfully completed without conversion to
      traditional laparoscopic conversion. The tumors ranged from 1 cm to 4.7 cm (mean,
      2.3 cm). The operative time was 71-257 minutes (mean, 121 minutes). Most patients
      (n = 8) had minimal blood loss; the other three patients had a blood loss of 150
      mL, 100 mL, and 100 mL. The mean hospital stay was 3 days (range, 1-6 days).
      There were no perioperative or postoperative complications. Pathological
      examinations revealed negative surgical margins in all specimens. All patients
      with Conn's syndrome had an improvement in blood pressure and normalization of
      plasma renin activity and serum aldosterone levels; all patients were free of
      potassium supplementation. CONCLUSION: Our results clearly demonstrate that LESS
      retroperitoneal partial adrenalectomy can be performed safely and effectively
      using a custom-made single-access platform and standard laparoscopic instruments.

PMID- 24661452
TI  - Economic evaluation in health care: a modern day quagmire.

PMID- 24661453
TI  - Frailty in left ventricular assist device destination therapy: putting a new
      motor in a rickety old car running out of gas?

PMID- 24661454
TI  - Systolic blood pressure influences the interpretation of cardiopulmonary exercise
      tests and helps identify a very high-risk cohort of heart failure patients.
AB  - BACKGROUND: Ventilatory inefficiency (high volume of expired air/volume of carbon
      dioxide eliminated [Ve/Vco2] slope), and impaired exercise tolerance (low peak
      volume of oxygen consumption) obtained from cardiopulmonary exercise testing
      (CPX) strongly predict mortality in heart failure (HF) patients; however, other
      CPX variables may also contain prognostic information. Therefore, the purpose of
      this study was to determine the prognostic power of the aggregate of CPX data.
      METHODS: The study prospectively monitored 390 patients referred for cardiac
      transplantation evaluation for 10 years for events (death, urgent transplant,
      left ventricular assist devices). Cox regression was used to analyze 18 CPX
      variables to identify the best survival model. RESULTS: Ve/Vco2 slope was the
      most powerful mortality predictor, and only resting systolic blood pressure (SBP)
      added additional independent prognostic power when expressed at its threshold
      effect value as SBP <= 100 mm Hg. Patients with low SBP had a greater risk than
      those who were within the next higher quartile of Ve/Vco2 slope with SBP > 100 mm
      Hg. A very high-risk cohort included 9% of the population that had a Ve/Vco2
      slope > 41 and SBP <= 100 mm Hg and an associated 2-year event rate of 67%;
      conversely, a low-risk cohort had a Ve/Vco2 slope <= 30 and SBP >100 mm Hg and
      associated 2-, 5-, and 10-year event rates of 5%, 12%, and 30%, respectively.
      CONCLUSIONS: Ve/Vco2 slope was the best individual predictive CPX variable and
      its interpretation was significantly altered by the presence of hypotension. An
      algorithm combining these CPX variables identifies a HF population at very high
      risk of early death and warranting advanced therapies.

PMID- 24661451
TI  - Report from a consensus conference on primary graft dysfunction after cardiac
      transplantation.
AB  - Although primary graft dysfunction (PGD) is fairly common early after cardiac
      transplant, standardized schemes for diagnosis and treatment remain contentious.
      Most major cardiac transplant centers use different definitions and parameters of
      cardiac function. Thus, there is difficulty comparing published reports and no
      agreed protocol for management. A consensus conference was organized to better
      define, diagnose, and manage PGD. There were 71 participants (transplant
      cardiologists, surgeons, immunologists and pathologists), with vast clinical and
      published experience in PGD, representing 42 heart transplant centers worldwide.
      State-of-the-art PGD presentations occurred with subsequent breakout sessions
      planned in an attempt to reach consensus on various issues. Graft dysfunction
      will be classified into primary graft dysfunction (PGD) or secondary graft
      dysfunction where there is a discernible cause such as hyperacute rejection,
      pulmonary hypertension, or surgical complications. PGD must be diagnosed within
      24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD
      right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe
      grades depending on the level of cardiac function and the extent of inotrope and
      mechanical support required. Agreed risk factors for PGD include donor,
      recipient, and surgical procedural factors. Recommended management involves
      minimization of risk factors, gradual increase of inotropes, and use of
      mechanical circulatory support as needed. Retransplantation may be indicated if
      risk factors are minimal. With a standardized definition of PGD, there will be
      more consistent recognition of this phenomenon and treatment modalities will be
      more comparable. This should lead to better understanding of PGD and
      prevention/minimization of its adverse outcomes. 

PMID- 24661455
TI  - Sleep disordered breathing and airway disease in primary ciliary dyskinesia.
AB  - BACKGROUND AND OBJECTIVE: Sleep-disordered breathing (SDB) may develop in primary
      ciliary dyskinesia (PCD), leading to these diseases worsening one another.
      METHODS: Sixteen stable PCD patients (4.9-17.2 years) and 42 controls underwent
      overnight respiratory polysomnography (rPSG) and Sleep Disturbances Scale for
      Children (SDSC). In PCD we assessed nasal endoscopy, pulmonary function tests and
      chest high-resolution computed tomography (HRCT). RESULTS: Compared with
      controls, PCD had higher obstructive apnoea (4.7 vs 0.2, P < 0.001), central
      apnoea (0.8 vs 0.2, P < 0.001), hypopnoea (1.8 vs 0.2, P < 0.001), apnoea
      hypopnoea (7.8 vs 0.6, P < 0.001), oxygen desaturation indexes (ODI; 0.7 vs 0.2,
      P = 0.002), and mean oxygen desaturation (4% vs 1%, P < 0.001), while mean and
      nadir oxygen saturation (97.1% vs 98.1, P < 0.001) (93% vs 97.2%, P < 0.001) were
      lower, respectively. In PCD, SDSC was unrelated to rPSG (P > 0.05), with total
      score and subscores of disorders in initiating and maintaining sleep, and sleep
      wake transition lower than controls. PCD patients had chronic rhinosinusitis
      (100%) and adenoidal hypertrophy (50%). Total HRCT score was 7 (range 0-14). ODI
      correlated with functional residual capacity (r = 0.8, P = 0.02), total HRCT (r =
      0.6, P = 0.03) and peribronchial thickening scores (r = 0.7, P = 0.02). Oxygen
      saturation was associated with bronchiectasis severity score (r = -0.6, P =
      0.02). CONCLUSIONS: PCD's parents may underestimate SDB. As nocturnal
      desaturation is associated with lung function and structure abnormalities, SDB
      may significantly contribute to pulmonary morbidity.

PMID- 24661456
TI  - Decoding the individual finger movements from single-trial functional magnetic
      resonance imaging recordings of human brain activity.
AB  - Multivariate pattern classification analysis (MVPA) has been applied to
      functional magnetic resonance imaging (fMRI) data to decode brain states from
      spatially distributed activation patterns. Decoding upper limb movements from non
      invasively recorded human brain activation is crucial for implementing a brain
      machine interface that directly harnesses an individual's thoughts to control
      external devices or computers. The aim of this study was to decode the individual
      finger movements from fMRI single-trial data. Thirteen healthy human subjects
      participated in a visually cued delayed finger movement task, and only one slight
      button press was performed in each trial. Using MVPA, the decoding accuracy (DA)
      was computed separately for the different motor-related regions of interest. For
      the construction of feature vectors, the feature vectors from two successive
      volumes in the image series for a trial were concatenated. With these spatial
      temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best
      subject) for the contralateral primary somatosensory cortex and a 46.0% average
      DA (71.0% for the best subject) for the contralateral primary motor cortex; both
      of these values were significantly above the chance level (20%). In addition, we
      implemented searchlight MVPA to search for informative regions in an unbiased
      manner across the whole brain. Furthermore, by applying searchlight MVPA to each
      volume of a trial, we visually demonstrated the information for decoding, both
      spatially and temporally. The results suggest that the non-invasive fMRI
      technique may provide informative features for decoding individual finger
      movements and the potential of developing an fMRI-based brain-machine interface
      for finger movement. 

PMID- 24661457
TI  - Erlotinib-induced complete response in a patient with epidermal growth factor
      receptor wild-type lung adenocarcinoma after chemotherapy failure: a case report.
AB  - INTRODUCTION: The efficacy of erlotinib in advanced non-small-cell lung cancer
      has been demonstrated in several trials, but only two cases of complete and
      prolonged response in wild-type epidermal growth factor receptor locally advanced
      lung cancer have been published. CASE PRESENTATION: We discuss a case of a 67
      year-old Caucasian man, a former heavy cigarette smoker, with a diagnosis of wild
      type epidermal growth factor receptor locally advanced adenocarcinoma. After
      platinum-based doublet chemotherapy, when a progression of disease had occurred,
      a second-line therapy with erlotinib was started. We observed a progressive
      reduction of his lung lesion during erlotinib treatment until there was a
      complete clinical response. CONCLUSIONS: This case is interesting for the choice
      of second-line treatment in non-small-cell lung cancer and, moreover, for the
      possibility of a complete and prolonged response to erlotinib even in patients
      without the activating mutation of epidermal growth factor receptor.

PMID- 24661458
TI  - Distribution and sources of polycyclic aromatic hydrocarbons in the surface
      sediments of Gorgan Bay, Caspian Sea.
AB  - The level and source of 16 polycyclic aromatic hydrocarbons (PAHs) were
      investigated in the surface sediments from the Gorgan Bay, Caspian Sea. The sum
      of 16 PAHs (SigmaPAH16) concentrations varied from 107.87 to 516.18 ng g(-1)dry
      weight, with average value of 270.96 +/- 150.47 ng g(-1)dry weight. Ecological
      risk assessment of PAHs, indicated that adverse biological effects caused by
      acenaphthene, naphthalene, fluoranthene and Pyrene occasionally and frequently
      may take place in the sediments of Gorgan Bay. PAHs source identification
      demonstrated that the PAHs come from mixed and pyrogenic origin.

PMID- 24661459
TI  - Assessment of mercury and selenium tissular concentrations and total mercury body
      burden in 6 Steller sea lion pups from the Aleutian Islands.
AB  - Concentrations of total mercury ([THg]) and selenium ([TSe]) were measured in
      several tissue compartments in Steller sea lion (Eumetopias jubatus) pups; in
      addition we determined specific compartment and body burdens of THg.
      Compartmental and body burdens were calculated by multiplying specific
      compartment fresh weight by the [THg] (summing compartment burdens equals body
      burden). In all 6 pup tissue sets (1) highest [THg] was in hair, (2) lowest [THg]
      was in bone, and (3) pelt, muscle and liver burdens contributed the top three
      highest percentages of THg body burden. In 5 of 6 pups the Se:Hg molar ratios
      among compartments ranged from 0.9 to 43.0. The pup with the highest hair [THg]
      had Se:Hg molar ratios in 9 of 14 compartments that were ? 0.7 potentially
      indicating an inadequate [TSe] relative to [THg].

PMID- 24661460
TI  - Acute hypoxic exposure affects gamete quality and subsequent fertilization
      success and embryonic development in a serpulid polychaete.
AB  - Hypoxia likely compromises the reproductive success of those marine organisms
      carrying out external fertilization because their gametes and embryos are
      inevitably exposed to the external environment. Hydroides elegans, a dominant
      serpulid polychaete in Hong Kong waters, can spawn throughout the year but the
      number of recruits drops during summer when hypoxia commonly occurs. This study
      attempted to explain such observation by investigating the gamete quality,
      including sperm motility, egg size, complexity and viability, after 1-h hypoxic
      exposure (1 mg O2 l(-1)). In addition, how gamete quality affects fertilization
      success and embryonic development was examined. After 1-h hypoxic exposure, sperm
      motility was significantly reduced, compromising fertilization success. Although
      the eggs remained viable, more malformed embryos and retarded embryonic
      development were observed. We interpreted that the harmful effect of hypoxia on
      embryonic development was attributed to the teratogenicity and induced oxidative
      stress, ultimately causing the reduction in recruitment during summer.

PMID- 24661462
TI  - Developing and evaluating complex interventions.

PMID- 24661461
TI  - Treatment preferences amongst physical therapists and chiropractors for the
      management of neck pain: results of an international survey.
AB  - BACKGROUND: Clinical practice guidelines on the management of neck pain make
      recommendations to help practitioners optimize patient care. By examining the
      practice patterns of practitioners, adherence to CPGs or lack thereof, is
      demonstrated. Understanding utilization of various treatments by practitioners
      and comparing these patterns to that of recommended guidelines is important to
      identify gaps for knowledge translation and improve treatment regimens. AIM: To
      describe the utilization of interventions in patients with neck pain by
      clinicians. METHODS: A cross-sectional international survey was conducted from
      February 2012 to March 2013 to determine physical medicine, complementary and
      alternative medicine utilization amongst 360 clinicians treating patients with
      neck pain. RESULTS: The survey was international (19 countries) with Canada
      having the largest response (38%). Results were analyzed by usage amongst
      physical therapists (38%) and chiropractors (31%) as they were the predominant
      respondents. Within these professions, respondents were male (41-66%) working in
      private practice (69-95%). Exercise and manual therapies were consistently (98
      99%) used by both professions but tests of subgroup differences determined that
      physical therapists used exercise, orthoses and 'other' interventions more, while
      chiropractors used phototherapeutics more. However, phototherapeutics (65%),
      Orthoses/supportive devices (57%), mechanical traction (55%) and sonic therapies
      (54%) were not used by the majority of respondents. Thermal applications (73%)
      and acupuncture (46%) were the modalities used most commonly. Analysis of
      differences across the subtypes of neck pain indicated that respondents utilize
      treatments more often for chronic neck pain and whiplash conditions, followed by
      radiculopathy, acute neck pain and whiplash conditions, and facet joint
      dysfunction by diagnostic block. The higher rates of usage of some interventions
      were consistent with supporting evidence (e.g. manual therapy). However, there
      was moderate usage of a number of interventions that have limited support or
      conflicting evidence (e.g. ergonomics). CONCLUSIONS: This survey indicates that
      exercise and manual therapy are core treatments provided by chiropractors and
      physical therapists. Future research should address gaps in evidence associated
      with variable practice patterns and knowledge translation to reduce usage of some
      interventions that have been shown to be ineffective.

PMID- 24661463
TI  - Influence of family environment on childhood stunting.

PMID- 24661464
TI  - Clinician versus machine: reliability and responsiveness of motor endpoints in
      Parkinson's disease.
AB  - BACKGROUND: Enhancing the reliability and responsiveness of motor assessments
      required to demonstrate therapeutic efficacy is a priority for Parkinson's
      disease (PD) clinical trials. The objective of this study is to determine the
      reliability and responsiveness of a portable kinematic system for quantifying PD
      motor deficits as compared to clinical ratings. METHODS: Eighteen PD patients
      with subthalamic nucleus deep-brain stimulation (DBS) performed three tasks for
      evaluating resting tremor, postural tremor, and finger-tapping speed, amplitude,
      and rhythm while wearing a wireless motion-sensor unit (Kinesia) on the more
      affected index finger. These tasks were repeated three times with DBS turned off
      and at each of 10 different stimulation amplitudes chosen to yield small changes
      in treatment response. Each task performance was video-recorded for subsequent
      clinician rating in blinded, randomized order. Test-retest reliability was
      calculated as intraclass correlation (ICC) and sensitivity was calculated as
      minimal detectable change (MDC) for each DBS amplitude. RESULTS: ICCs for Kinesia
      were significantly higher than those for clinician ratings of finger-tapping
      speed (p < 0.0001), amplitude (p < 0.0001), and rhythm (p < 0.05), but were not
      significantly different for evaluations of resting or postural tremor. Similarly,
      Kinesia scores yielded a lower MDC as compared with clinician scores across all
      finger-tapping subscores (p < 0.0001), but did not differ significantly for
      resting and postural tremor. CONCLUSIONS: The Kinesia portable kinematic system
      can provide greater test-retest reliability and sensitivity to change than
      conventional clinical ratings for measuring bradykinesia, hypokinesia, and
      dysrhythmia in PD patients.

PMID- 24661465
TI  - Efficacy and safety of deferiprone for the treatment of pantothenate kinase
      associated neurodegeneration (PKAN) and neurodegeneration with brain iron
      accumulation (NBIA): results from a four years follow-up.
AB  - OBJECTIVE: To evaluate the long-term effect of Deferiprone (DFP) in reducing
      brain iron overload and improving neurological manifestations in patients with
      NBIA. METHODS: 6 NBIA patients (5 with genetically confirmed PKAN), received DFP
      solution at 15 mg/kg po bid. They were assessed by UPDRS/III and UDRS scales and
      blinded video rating, performed at baseline and every six months. All patients
      underwent brain MRI at baseline and during follow up. Quantitative assessment of
      brain iron was performed with T2* relaxometry, using a gradient multi-echo T2*
      sequence. RESULTS: After 48 months of treatment clinical rating scales and
      blinded video rating indicated a stabilization in motor symptoms in 5/6 Pts. In
      the same subjects MRI evaluation showed reduced hypointensity in the globus
      pallidus (GP); quantitative assessment confirmed a significant increment in the
      T2* value, and hence reduction of the iron content of the GP. CONCLUSION: The
      data from our 4-years follow-up study confirm the safety of DFP as a chelator
      agent for iron accumulation. The clinical stabilization observed in 5/6 of our
      patients suggests that DFP may be a reasonable therapeutic option for the
      treatment of the neurological manifestations linked with iron accumulation and
      neurodegeneration, especially in adult patients at early stage of the disease.
      (Clinicaltrials.gov identifier: NTC00907283).

PMID- 24661466
TI  - Variant R244H in Na+/Mg2+ exchanger SLC41A1 in Taiwanese Parkinson's disease is
      associated with loss of Mg2+ efflux function.
AB  - BACKGROUND: Sequence variants in SLC41A1 have been reported to be associated with
      Parkinson's disease (PD). This study investigates whether the genetic variants in
      SLC41A1 contribute to Taiwanese PD. METHODS: We sequenced SLC41A1 cDNA fragments
      from 80 patients with early onset PD. A cohort of PD and ethnically matched
      controls were examined for the sequence variant. The effect of variation on
      Mg(2+) homeostasis was further examined using stably induced 293 cells expressing
      recombinant wild type and variant SLC41A1. RESULTS: A novel heterozygous R244H in
      the SLC41A1 gene was identified in one early onset PD patient, which not present
      either in 479 PD patients or 525 normal controls with age onset >50. Both wild
      type and R244H SLC41A1-V5-His proteins were co-localized to areas of the plasma
      membrane that were stained using wheat germ agglutinin (WGA). Fluorescent probe
      mag-fluo-4 staining indicated that R244H SLC41A1 is dysfunctional in Mg(2+)
      efflux. CONCLUSIONS: This study has shown loss of Mg(2+) efflux function
      consequent to SLC41A1 R244H variant and SLC41A1 coding variants seem to be rare
      in Taiwanese PD.

PMID- 24661467
TI  - Reluctance to start medication for Parkinson's disease: a mutual misunderstanding
      by patients and physicians.
AB  - Reluctance to start medication has never been investigated before in PD. We
      studied reluctance to start medication for PD motor symptoms, namely its
      prevalence, underlying reasons, drug-specificity, and associated delay in the
      start of PD medication. A cross-sectional observational international study was
      conducted. Patients with a clinical diagnosis of PD advised to start
      antiparkinsonian medication in the previous 5 years were invited to complete a
      questionnaire in three centers located in North America and Europe. An electronic
      online survey was sent to physicians through the mailing list of the Movement
      Disorder Society. 469 participants (201 PD patients, 268 physicians). 40.2% (n =
      82) of the patients reported reluctance to start medication, but 88.6% (n =
      234/264) of the physicians estimated that <=20% of their patients with PD had
      been reluctant to start medication. The most common reasons reported by patients
      were the fear of side effects (n = 35, 55.6%), followed by non-acceptance of
      diagnosis (n = 23, 36.5%); fear of a temporally limited benefit was more commonly
      selected by physicians (n = 92/267, 34.5%). Patients indicated reluctance to
      start DAs more frequently compared with L-DOPA (OR: 2.22, 95% CI: 1.30, 9.03; p =
      0.013) while physicians perceived L-DOPA to be associated with more reluctance
      (OR: 4.7, 95% CI: 3.41; 6.59; p < 0.0001). Patients with PD and physicians have a
      different perspective on the issue of reluctance to start medication. There is a
      need to bring physicians and patients with PD closer to a shared vision of the
      problem reluctance to start medication. 

PMID- 24661468
TI  - Psychogenic axial myoclonus: clinical features and long-term outcome.
AB  - BACKGROUND: It has been increasingly recognized that the majority of patients
      with a diagnosis of idiopathic propriospinal myoclonus have either a subsequent
      clinical course or electrophysiological features indicating that the likely
      etiology is psychogenic. However, the clinical features of psychogenic axial
      myoclonus and the long-term outcome have not yet well characterized. PATIENTS AND
      METHODS: Here we describe clinical findings with representative videos and long
      term outcomes of 76 patients with an electrophysiologically established diagnosis
      of psychogenic axial myoclonus. RESULTS: Thirty-seven patients were male. Mean
      age at onset of symptoms was 40.1 +/- 15.1 years. Thirty-two patients (42.1%)
      presented with isolated axial myoclonus, while 44 patients (57.9%) presented
      additional features, including involvement of face or limb. In all patients but
      six (7.9%), the axial myoclonus was in flexion. In more than one-third of
      patients (42.1%), jerks were multifocal, meaning that there was no clear
      stereotyped pattern of jerks. Comparison between groups stratified according to
      the clinical outcome, revealed "delay of diagnosis" as the only predictor of
      worse outcome. DISCUSSION: We describe here the clinical features and long-term
      outcome on the largest series of patients with psychogenic axial myoclonus
      reported in the literature. The description of our series highlights a number of
      clinical features, which may help neurologists to reach a correct diagnosis on
      clinical grounds alone. Delay in diagnosis of a psychogenic disorder has a
      negative effect on long-term outcome.

PMID- 24661469
TI  - Knowledge and reported confidence of final year midwifery students regarding
      giving advice on contraception and sexual health.
AB  - OBJECTIVE: this study explored the views of three cohorts of final year midwifery
      students, regarding their confidence in giving advice to women on contraception
      and sexual health in the postnatal period. The project also investigated
      knowledge of contraception using a factual quiz, based on clinical scenarios
      regarding contraception and sexual health in the postpartum period. DESIGN: a
      mixed method design using qualitative data from focus groups, and mixed
      qualitative and quantitative data from a paper based questionnaire was used.
      SETTING: the project was carried out in one higher educational institution in
      England. FINDINGS: findings demonstrate that expressed confidence varies
      according to contraceptive method, with most confidence being reported when
      advising on the male condom. The findings of the factual quiz indicate that
      students applied theoretical knowledge poorly in a practically oriented context.
      These findings also indicated that most students limited advice to general
      advice. KEY CONCLUSIONS: the paper concludes that midwifery students need more
      practically oriented education in contraception and sexual health, and that the
      role of mentors is very important in helping students feel confident when giving
      advice in this area.

PMID- 24661470
TI  - Implementation of evidence-based falls prevention in clinical services for high
      risk clients.
AB  - RATIONALE, AIMS AND OBJECTIVES: The extent to which best practice for falls
      prevention is being routinely delivered by health care providers for community
      dwelling older adults is unclear. We investigated falls prevention practice among
      Hospital Admission Risk Programs (HARP) that provide and coordinate specialized
      health care for people at high risk of hospitalization. METHOD: Cross-sectional
      survey of all HARP services in Victoria, excluding one paediatric programme (n =
      34). The questionnaire focused upon medication review and exercise prescription,
      as these are the evidence-based falls interventions with a good fit with HARP
      services. RESULTS: Completed questionnaires were received from 24 programmes
      (70.6%) that service 15,250 older clients (60+ years). All except one programme
      screened for medicine use; however, a lower proportion (65% of those that screen)
      target falls risk medications. Among the 17 programmes responding to the exercise
      prescription question, all routinely include strengthening exercises, and almost
      all (n = 15) include flexibility, endurance training and movement of the centre
      of gravity. A lesser proportion (71%) includes reducing the need for upper limb
      support. The majority of services (88%) undertake falls risk assessments, and all
      of these either make referral appointments for clients or refer to other services
      that make referral appointments for clients. Follow-up of appointments and the
      resulting recommendations was high. CONCLUSION: Screening for falls risk
      medications could be improved and staff training in exercise prescription for
      balance challenge in this high-risk group may be needed. Although evidence-based
      falls prevention practice within Victorian HARP services appears strong, the
      effect on falls risk may not be as high as that achieved in randomized trials.

PMID- 24661471
TI  - Wandering and dementia.
AB  - Wandering represents one of many behavioural problems occurring in people with
      dementia. To consider the phenomenon of wandering behaviour in demented patients,
      we conducted searches using Medline and Google Scholar to find relevant articles,
      chapters, and books published since 1975. Search terms used included 'wandering',
      'behavioural and psychological symptoms', 'dementia', 'nursing', and
      'elopements'. Publications found through this indexed search were reviewed for
      further relevant references. The term 'wandering' covers different types of
      behaviour, including aimless movement without a discernible purpose. It is
      associated with a variety of negatives outcomes. The aetiology of wandering is
      poorly understood and it remains an unsolved riddle. Wandering is an acutely
      distressing problem worldwide, both for the patients and caregivers, and it is a
      major reason for nursing home admission. Evidence on the effectiveness of
      pharmacological and non-pharmacological interventions is limited. It is possible
      that management of coexistent psychopathology would help to ameliorate this
      problematic behavioural disorder. 

PMID- 24661472
TI  - Immunological modes of pregnancy loss: inflammation, immune effectors, and
      stress.
AB  - Inflammatory immune response plays a key role in reproductive failures such as
      multiple implantation failures (MIF), early pregnancy loss, and recurrent
      pregnancy losses (RPL). Cellular immune responses particularly mediated by
      natural killer (NK), and T cells are often dysregulated in these conditions.
      Excessive or inappropriate recruitment of peripheral blood NK cells to the uterus
      may lead to cytotoxic environment in utero, in which proliferation and
      differentiation of trophoblast is hampered. In addition, inadequate angiogenesis
      by uterine NK cells often leads to abnormal vascular development and blood flow
      patterns, which, in turn, leads to increased oxidative stress or ischemic changes
      in the invading trophoblast. T-cell abnormalities with increased Th1 and Th17
      immunity, and decreased Th2 and T regulatory immune responses may play important
      roles in RPL and MIF. A possible role of stress in inflammatory immune response
      is also reviewed. 

PMID- 24661473
TI  - Psychosocial interventions for suicidal ideation, plans, and attempts: a database
      of randomised controlled trials.
AB  - BACKGROUND: Research in suicide prevention using psychosocial interventions is
      rapidly advancing. However, randomised controlled trials are published across a
      range of medical, psychological and sociology journals, and it can be difficult
      to locate a full set of research studies. In this paper, we present a database of
      randomised controlled outcome studies on psychosocial interventions targeting
      suicidal behaviour. The database is updated annually and can be accessed by
      contacting the corresponding author. DESCRIPTION: A comprehensive literature
      search of the major bibliographical databases (PsycINFO; PubMed; Cochrane Central
      Register of Controlled Trials) was conducted for articles published between 1800
      to July 30 2013, and examined reference lists of previous relevant reviews and
      included papers to locate additional references. Studies were included if they
      featured a randomised controlled design in which the effects of a psychosocial
      intervention were compared to a control condition (no intervention, attention
      placebo, wait-list, treatment-as-usual [TAU]), another psychosocial intervention
      or a pharmacological intervention. In total, 12,250 abstracts were identified. Of
      these, 131 studies met eligibility criteria and were included. Each paper was
      then coded into categories of participant characteristics (age, gender, formal
      diagnosis, primary reason for recruitment); details of the intervention
      (recruitment setting, content, intervention setting, administering individual,
      delivery type, delivery format, delivery frequency, delivery length); and study
      characteristics (control and experimental conditions, primary outcome/s,
      secondary outcome/s, follow-up period). One paper has been published from the
      database using studies collected and coded prior to 2012. CONCLUSION: The
      database and listing of 131 studies is available for use by suicide prevention
      researchers. It provides a strong starting point for systematic reviews and meta
      analyses of treatments and interventions. It will be updated yearly by
      researchers funded through the Australian National Health and Medical Research
      Council Centre for Research Excellence for Suicide Prevention (CRESP), located at
      the Black Dog Institute, Australia. This database adds to the evidence base of
      best-practice psychosocial interventions for suicidal behaviour and prevention.

PMID- 24661474
TI  - Twitter response to the United States Preventive Services Task Force
      recommendations against screening with prostate-specific antigen.
AB  - OBJECTIVE: To examine public and media response to the draft (October 2011) and
      finalised (May 2012) recommendations of the United States Preventive Services
      Task Force (USPSTF) against prostate-specific antigen (PSA) testing via Twitter,
      a popular social network with over 200 million active users. MATERIALS AND
      METHODS: We used a mixed-methods design to analyse posts on Twitter, known as
      'tweets'. Using the search term 'prostate cancer', we archived tweets in the 24-h
      periods following the release of both the draft and the finalised USPSTF
      recommendations. We recorded tweet rate per h and developed a coding system to
      assess the type of user and sentiment expressed in tweets and linked articles.
      RESULTS: After the draft and finalised USPSTF recommendations were released, 2042
      and 5357 tweets focused on the USPSTF report, respectively. The tweet rate nearly
      doubled within 2 h of both announcements. Fewer than 10% of tweets expressed an
      opinion about screening, and the majority of these were pro-screening during both
      periods. By contrast, anti-screening articles were tweeted more frequently in
      both the draft and finalised study periods. Between the draft and the finalised
      recommendations, the proportion of anti-screening tweets and anti-screening
      article links increased (P = 0.03 and P < 0.01, respectively). CONCLUSIONS: There
      was increased Twitter activity surrounding the USPSTF draft and finalised
      recommendations. The percentage of anti-screening tweets and articles appeared to
      increase, perhaps due to the interval public comment period. Despite this, most
      tweets did not express an opinion, suggesting a missed opportunity in this
      important arena for advocacy.

PMID- 24661476
TI  - Hyponatraemia in cancer: association with type of cancer and mortality.
AB  - Hyponatraemia is common in patients with cancer. The objectives of this study are
      to investigate the severity distribution of hyponatraemia and its association
      with mortality. We retrospectively reviewed medical records for patients admitted
      to a national centre for cancer care and research in Qatar between 2008 and 2012.
      A model was built through multivariate analyses to investigate the role of
      hyponatraemia in mortality. Patients were grouped into those who had moderate
      severe hyponatraemia (Na < 130) and those who only had normal-mild hyponatraemia
      (Na >= 130). A total of 2048 patients were included in this study. Prostate
      (57.1%), pancreatic (50%), liver (49%) and lung (40.2%) cancers showed the
      highest frequency of moderate-severe hyponatraemia, while breast cancer showed
      the lowest frequency at 23.5%. In the multivariate analyses, patients with
      moderate-severe hyponatraemia (Na < 130 mmol/L) were 4.28 times more likely to
      die than those with normal-mild hyponatraemia (Na >= 130) (P < 0.05). The present
      study shows that hyponatraemia is a common electrolyte disturbance among
      hospitalised patients with cancer diagnoses. The severity of hyponatraemia was a
      statistically significant independent factor associated with higher in-hospital
      mortality. This is in accordance with the reported literature and emphasises the
      importance of early diagnosis and correction of hyponatraemia.

PMID- 24661475
TI  - Comparative effectiveness of telaprevir-based triple therapy in patients with
      chronic hepatitis C.
AB  - OBJECTIVE: To examine the effectiveness and tolerability of triple therapy with
      pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with
      chronic hepatitis C receiving treatment in an academic practice setting and in a
      more clinically diverse population compared with patients receiving treatment in
      phase 3 trials. PATIENTS AND METHODS: A prospective database of all patients with
      viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1,
      2012, was queried to identify treatment-naive and -experienced patients with
      chronic hepatitis C receiving dual and triple therapies. On-treatment response
      categories included rapid virologic response, extended rapid virologic response,
      early virologic response, and sustained virologic response. These patients were
      compared with matched controls, namely, patients who underwent dual therapy with
      p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior
      treatment. RESULTS: There were 55 patients who received triple therapy and met
      the eligibility criteria, consisting of treatment-naive (n=35) and -experienced
      patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who
      terminated the treatment early, 2). Rapid virologic response was achieved in 41%
      of the patients, extended rapid virologic response in 41%, and early virologic
      response in 75%. Sustained virologic response was observed in 51% (18/35) of
      treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and
      56% (5/9) of those with prior relapse. Corresponding results after dual therapy
      were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in
      the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and
      3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert
      mg/dL to mmol/L, multiply values by 0.0259). CONCLUSION: Telaprevir-based triple
      therapy in clinical practice is considerably more effective than dual therapy
      with p-IFN and RBV despite the significant degree of anemia that complicated
      therapy, requiring RBV dose reduction and erythropoietin support.

PMID- 24661477
TI  - ICU overflow in the PACU.

PMID- 24661478
TI  - Association of abdominal obesity in children with perioperative respiratory
      adverse events.
AB  - BACKGROUND/PURPOSE: Waist circumference (WC), a measure of abdominal obesity, is
      associated with several chronic disorders. Less is known about the association
      between WC and acute perioperative adverse events. The purpose of the present
      investigation was to test the hypothesis that abdominal obesity increases the
      occurrence of perioperative adverse events in children undergoing elective,
      noncardiac surgeries. DESIGN: Prospective observational study. METHODS: We
      studied the association between WC and perioperative adverse events in children
      aged 6 to 18 years who underwent elective noncardiac surgeries at our
      institution. Patients were considered to have abdominal obesity if WC was 90th
      percentile or greater for age and gender. Subsequently, univariate factors
      associated with abdominal obesity were explored and then odds ratios for the
      occurrence of perioperative respiratory adverse events were calculated from
      logistic regression after controlling for clinically pertinent covariates.
      RESULTS: Among 1,102 patients, the prevalence of abdominal obesity was 23.1%. WC
      was positively correlated with age and measured anthropometric parameters.
      Composite perioperative adverse events were more frequent in children with
      abdominal obesity. After adjusting for several clinically relevant risk factors,
      abdominal obesity independently predicted increased relative odds of respiratory
      adverse events (OR = 2.35, 95% CI = 1.6 to 3.5, P < .001). Abdominal obesity was
      also associated with prolonged postanesthesia care unit (PACU) length of stay.
      CONCLUSION: WC, a measure of abdominal obesity, is an independent predictor of
      perioperative respiratory adverse events in children undergoing elective
      noncardiac surgery. Furthermore, abdominal obesity was associated with prolonged
      PACU length of stay.

PMID- 24661479
TI  - Effects of therapeutic suggestion under anesthesia on outcomes in children post
      tonsillectomy.
AB  - INTRODUCTION: Tonsillectomy causes discomfort in children. Positive therapeutic
      suggestions (TS) may be given to patients while they are emerging from general
      anesthesia as a potential tool to decrease distress. PURPOSE: This study examined
      impact of TS on outcomes, when delivered to children emerging from general
      anesthesia post tonsillectomy. DESIGN: A double blinded randomized controlled
      trial was conducted with 94 patient/parent pairs. METHODS: TS and noise
      recordings were played via headphones post tonsillectomy upon arrival to the Post
      Anesthesia Care Unit until the child showed signs of waking. FINDINGS: Pain
      scores at 30 minutes post extubation show significantly lower pain in the TS
      group, P = .04 (Mann Whitney U for independent samples). The TS group had 70%
      increased likelihood of receiving less intravenous (IV) opioid. CONCLUSION: TS
      may help lower pain in children post tonsillectomy and decrease demand for IV
      opioid pain management in the 4- to 8-year-old tonsillectomy population.

PMID- 24661480
TI  - Caring for prisoners-patients: a quandary for registered nurses.
AB  - PURPOSE: The purpose of this study was to unveil the complexity of registered
      nurse (RN) care for prisoner-patients in an acute care perioperative setting.
      DESIGN: The study design was based on phenomenology and the philosophy of Hans
      George Gadamer. METHOD: This study used researcher journaling and two audio-taped
      in-depth interviews with each of the 12 nurse participants. FINDINGS: Five key
      fused horizons or joint understandings emerged that resonated for all
      participants. They were the following: * RNs give prisoner-patients perfunctory
      care; * Prisoner-patient care is reactive; * Caring for prisoner-patients is
      emotionally draining; * Knowing or imagining a prisoner-patient's crime creates
      practice dilemmas; and * Expressions of care straddle ideal and real caring
      perspectives. CONCLUSION: In the caring literature, caring is altruistically
      presented as an ideal that (ought to) guide RN interactions with patients.
      However, the study findings call into question the assumptions that are made
      about what it means to care and how RNs enact their caring role, particularly in
      vexatious situations.

PMID- 24661481
TI  - Patient and family member needs during the perioperative period.
AB  - PURPOSE: The purpose of this study was to determine the needs and experiences of
      patients and family members throughout the entire perioperative experience.
      DESIGN AND METHODS: Using a descriptive study design, a convenience sample of
      patients and family members were surveyed about their needs and how well those
      needs were met during the perioperative period. Survey questions were adapted
      from valid and reliable patient and family needs surveys. Rank order of patient
      and family needs were determined based on average item scores. FINDINGS: A total
      of 68 patients and 63 family members were surveyed over an 8-month period.
      Patient needs with the highest scores were related to pain and/or nausea
      management, having information about the condition after surgery, and treatment
      with respect and dignity. Family member needs with the highest scores were
      related to communication with the surgeon after the procedure, opportunities to
      ask questions and address concerns with hospital staff, and receiving information
      about the surgical procedure itself before coming to the hospital. Patients and
      family members perceived that their needs were met most of the time. CONCLUSIONS:
      Results of this survey identify the needs of patients and family members
      throughout the perioperative time period.

PMID- 24661482
TI  - Intensive care unit patients in the postanesthesia care unit: a case study
      exploring nurses' experiences.
AB  - PURPOSE: The purpose of this study was to understand the experiences of
      postanesthesia nurses caring for intensive care unit (ICU) patients in the
      postanesthesia care unit (PACU). DESIGN: Qualitative interpretive description.
      METHODS: Six PACU nurses participated in semi-structured interviews. Interviews
      were digitally recorded, transcribed verbatim, and analyzed using constant
      comparative analysis. Quality of the data collection and analysis process was
      maintained through constructing codes and themes jointly by several investigators
      and taking interpretive accounts back to participants. FINDING: Three main themes
      were constructed: expert mind-set, specialty practice, and identity and
      relationships. The expert mind-set described knowing but not doing and straddling
      concurrent foci and duties. Specialty practice entailed doing but not knowing and
      the unsupportive context that perpetuated this. Identity and relationships
      described the lost identity of postanesthesia nursing and tension in the
      relationships with ICU. CONCLUSIONS: Findings illuminate the challenges expert
      nurses face when an unplanned practice change is implemented.

PMID- 24661483
TI  - Surgical versus conservative interventions for treating ankle fractures in
      adults.

PMID- 24661484
TI  - Enhancing sleep in critically ill perianesthesia patients.

PMID- 24661485
TI  - Opioid-induced ventilatory impairment (OIVI).

PMID- 24661486
TI  - The toxicity of nursing.

PMID- 24661487
TI  - Antimicrobial prophylaxis for surgery--2014 update.

PMID- 24661488
TI  - Length of stay--discharge criteria.

PMID- 24661489
TI  - Your academic progression in nursing--no time like the present to start your
      plan!: guest editorial.

PMID- 24661490
TI  - Electrically facilitated translocation of protein through solid nanopore.
AB  - Nanopores have been proven as versatile single-molecule sensors for individual
      unlabeled biopolymer detection and characterization. In the present work, a
      relative large nanopore with a diameter of about 60 nm has been used to detect
      protein translocation driven by a series of applied voltages. Compared with
      previous studied small nanopores, a distinct profile of protein translocation
      through a larger nanopore has been characterized. First, a higher threshold
      voltage is required to drive proteins into the large nanopore. With the increase
      of voltages, the capture frequency of protein into the nanopore has been markedly
      enhanced. And the distribution of current blockage events is characterized as a
      function of biased voltages. Due to the large dimension of the nanopore, the
      adsorption and desorption phenomenon of proteins observed with a prolonged dwell
      time has been weakened in our work. Nevertheless, the protein can still be
      stretched into an unfolded state by increased electric forces at high voltages.
      In consideration of the high throughput of the large nanopore, a couple of
      proteins passing through the nanopore simultaneously occur at high voltage. As a
      new feature, the feasibility and specificity of a nanopore with distinct geometry
      have been demonstrated for sensing protein translocation, which broadly expand
      the application of nanopore devices. 

PMID- 24661491
TI  - Primary diffuse large B-cell lymphoma developing within a rectal tubular adenoma
      with low-grade dysplasia: a case report.
AB  - INTRODUCTION: Colorectal lymphomas represent only 5% to 10% of gastrointestinal
      lymphomas, after the stomach and small intestine. Primary lymphoma of the colon
      and rectum is an unusual observation, constituting only 0.2% to 0.5% of all
      malignant tumors arising from the colorectal region. Very little is known about
      the correlation between adenoma and lymphoma in the colorectal tract. We report
      here a rare case of diffuse large B-cell lymphoma developing within a solitary
      tubular adenoma with low-grade dysplasia of the rectum. CASE PRESENTATION: An 83
      year-old Caucasian man was referred to our hospital intermittent anal bleeding
      and irregular bowel. Colonoscopy revealed a 1cm solitary rectal polyp, which was
      completely removed by endoscopic resection. Histologic studies revealed low-grade
      intraepithelial dysplasia; the stroma of adenoma showed focal localization by
      highly proliferative lymphoid cells. Immunohistochemical analyses demonstrated
      that lymphoid cells were positive for CD20 and bcl2, whereas they were negative
      for CD3, CD5, CD10, CD23, CD30, CD138 and cyclin D1. Approximately 90% of the
      neoplastic cells reacted positively when stained with an antibody to Ki-67.
      Molecular studies showed the presence of a monoclonal immunoglobulin heavy chain
      gene rearrangement.To determine primary or secondary lymphoma localization,
      Dawson's criteria were applied to the case. A diagnosis of primary diffuse large
      B- lymphoma Ann Arbor stage 1A was established. Subsequently, the patient was
      referred to oncology to establish the stage and to select appropriate treatment.
      CONCLUSIONS: The case of diffuse large B-cell lymphoma developing within a
      tubular adenoma, as reported here, is considered a rare event. Little about the
      prognosis of primary colorectal lymphomas is available and therapeutic treatment
      protocol is unclear. This case report provides more information on the history
      and macroscopic appearance of lymphomas presenting in an unusual location. To
      report additional cases in the future would be helpful in redefining the
      diagnostic, prognostic and therapeutic approach.

PMID- 24661492
TI  - Reply to comments on "Identification of lead sources in residential environments:
      Sydney Australia" by Laidlaw et al. (2014).

PMID- 24661493
TI  - Dietary effects of Moringa oleifera leaf powder on growth, gastrointestinal
      morphometry and blood and liver metabolites in Sprague Dawley rats.
AB  - We investigated the effects of Moringa oleifera leaf powder (MOLP) as a dietary
      supplement on growth performance, gastrointestinal (GIT) morphometry and liver
      function using weanling Sprague Dawley rats to model humans under ad libitum and
      restricted feeding. An MOLP-based diet was generated by supplementing normal rat
      feed with the leaf powder at 20%. Four dietary regimens included normal rat feed
      fed at 20% of body mass (NRF: ad libitum), NRF fed at 14% of body mass (NRFR,
      restricted), Moringa-supplemented feeds fed at 20% and 14% of body mass (MOF: ad
      libitum and MOFR: restrictedly) respectively. Thirty-two pups were randomly
      assigned to the diets and fed for 5 weeks, after which they were fasted,
      euthanased and GIT viscera masses, lengths and histology were assessed. Blood was
      collected for metabolite and markers of liver function assays. Tibiae and femora
      lengths were used to determine linear growth. Rats fed the restricted diets had
      lower weekly body mass gains (p = 0.0001) than those on ad libitum feeding;
      however, they showed compensatory growth by 5 weeks. Terminally, the rats fed
      MOFR had shorter (p < 0.05) femora and tibiae than their counterparts on the
      other diets. Except on the caeca, diet had no effect on the absolute masses and
      lengths of GIT viscera. Relative to tibia length, rats on the MOF had
      significantly heavier stomachs and caeca and longer small and large intestines
      than their counterparts on NRF, but this was not supported histologically. Level
      of feeding and supplementation did not affect blood metabolite concentration,
      liver glycogen and lipid storage nor the plasma activities AST and ALP in the
      rats. Supplementing diets with MOLP under restricted access to feed (low
      calorific supply) might compromise linear growth.

PMID- 24661494
TI  - Fixational saccades alter the gap effect.
AB  - The reaction times of saccadic eye movements have been studied extensively as a
      probe for cognitive behavior controlled by large-scale cortical and subcortical
      neural networks. Recent studies have shown that the reaction times of targeting
      saccades toward peripheral visual stimuli are prolonged by fixational saccades,
      the largest miniature eye movements including microsaccades. We have shown
      previously that the frequency of fixational saccades is decreased by volitional
      action preparation controlled internally during the antisaccade paradigm (look
      away from a stimulus). Instead, here we examined whether fixational saccade
      modulation induced externally by sensory events could also account for targeting
      saccade facilitation by the same sensory events. When targeting saccades were
      facilitated by prior fixation stimulus disappearance (gap effect), fixational
      saccade occurrence was reduced, which could theoretically facilitate targeting
      saccades. However, such reduction was followed immediately by the rebound of
      fixational saccade occurrence in some subjects, which could eliminate potential
      benefits from the previous fixational saccade reduction. These results do not
      mean that fixational saccades were unrelated to the gap effect because they
      indeed altered that effect by delaying targeting saccade initiation on trials
      without the fixation gap more strongly than trials with it. Such changes might be
      attributed to the disruption of volitional saccade preparation because the
      frequency of fixational saccades observed in this study was associated with the
      ability of volitional control over antisaccade behavior. These results suggest
      that fixational saccades alter the gap effect on targeting saccade reaction
      times, presumably by disrupting volitional saccade commands. 

PMID- 24661495
TI  - Effect of drug reminder packaging on medication adherence: a systematic review
      revealing research gaps.
AB  - BACKGROUND: This was a systematic review of the literature in accordance with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      statement. Evidence mapping was used to reveal the effect of drug reminder
      packaging on medication adherence, to identify research gaps and to make
      suggestions for future research. METHODS: PubMed, Embase, CINAHL and PsycINFO
      were searched with an end date of September 2013 using the Medical Subject
      Headings (MeSH) term 'medication adherence' and 20 different search terms for
      'drug reminder packaging', limited to the English and German languages.
      Additional references were identified through cross-referencing. All prospective
      controlled trials with an intervention using drug reminder packaging for patients
      taking at least one medication without the assistance of a health-care
      professional were included in the evidence mapping of the effect of drug reminder
      packaging on adherence and outcomes according to the Economic, Clinical and
      Humanistic Outcomes (ECHO) model. RESULTS: A total of 30 studies met the
      inclusion criteria: 10 randomized controlled trials, 19 controlled clinical
      trials and 1 cohort study. Drug reminder packaging had a significant effect on at
      least one adherence parameter in 17 studies (57%). The methodological quality was
      strong in five studies. Two studies provided complete information. Clear research
      gaps emerged. CONCLUSIONS: Overall, the studies showed a positive effect of drug
      reminder packaging on adherence and clinical outcomes. However, poor reporting
      and important gaps like missing humanistic and economic outcomes and neglected
      safety issues limit the drawing of firm conclusions. Suggestions are made for
      future research.

PMID- 24661497
TI  - Effect of the infrastructure material on the failure behavior of prosthetic
      crowns.
AB  - OBJECTIVES: To evaluate the effect of infrastructure (IS) material on the
      fracture behavior of prosthetic crowns. METHODS: Restorations were fabricated
      using a metal die simulating a prepared tooth. Four groups were evaluated: YZ-C,
      Y-TZP (In-Ceram YZ, Vita) IS produced by CAD-CAM; IZ-C, In-Ceram Zirconia (Vita)
      IS produced by CAD-CAM; IZ-S, In-Ceram Zirconia (Vita) IS produced by slip-cast;
      MC, metal IS (control). The IS were veneered with porcelain and resin cemented to
      fiber-reinforced composite dies. Specimens were loaded in compression to failure
      using a universal testing machine. The 30 degrees  angle load was applied by a
      spherical piston, in 37 degrees C distilled water. Fractography was performed
      using stereomicroscope and SEM. Data were statistically analyzed with Anova and
      Student-Newman-Keuls tests (alpha=0.05). RESULTS: Significant differences were
      found between groups (p=0.022). MC showed the highest mean failure load,
      statistically similar to YZ-C. There was no statistical difference between YZ-C,
      IZ-C and IZ-S. MC and YZ-C showed no catastrophic failure. IZ-C and IZ-S showed
      chipping and catastrophic failures. The fracture behavior is similar to reported
      clinical failures. SIGNIFICANCE: Considering the ceramic systems evaluated, YZ-C
      and MC crowns present greater fracture load and a more favorable failure mode
      than In-Ceram Zirconia crowns, regardless of the fabrication type (CAD-CAM or
      slip-cast).

PMID- 24661496
TI  - Stringent requirement for spatial arrangement of extracellular matrix in
      supporting cell morphogenesis and differentiation.
AB  - BACKGROUND: In vitro experiments on the functional roles of extracellular matrix
      (ECM) components usually involve the culture of cells on surfaces coated with
      purified ECM components. These experiments can seldom recuperate the spatial
      arrangement of ECM found in vivo. In this study, we have overcome this obstacle
      by using histological sections of bovine Achilles tendon as cell culture
      substrates. RESULTS: We found that tendon sections can be viewed as a pre-formed
      block of ECM in which the collagen fibrils exhibited a spatial regularity
      unraveled in any artificially constructed scaffold. By carving the tendon at
      different angles relative to its main axis, we created different surfaces with
      distinct spatial arrangements of collagen fibrils. To assess the cellular
      responses to these surfaces, human mesenchymal stem cells (MSCs) were directly
      cultured on these sections, hence exposed to the collagen with different spatial
      orientations. Cells seeded on longitudinal tendon sections adopted a highly
      elongated and aligned morphology, and expressed an increased level of
      tenomodulin, suggesting that the collagen fibrils present in this section provide
      a microenvironment that facilitates cell morphogenesis and differentiation.
      However, MSC elongation, alignment and induction of tenomodulin diminished
      dramatically even as the sectioned angle changed slightly. CONCLUSION: Our
      results suggest that cell functions are influenced not only by the type or
      concentration of ECM components, but also by the precise spatial arrangements of
      these molecules. The method developed in this study offers a simple and robust
      way for the studying of cell-ECM interactions, and opens many research avenues in
      the field of matrix biology.

PMID- 24661498
TI  - Effects of donepezil dose escalation in Parkinson's patients with dementia
      receiving long-term donepezil treatment: an exploratory study.
AB  - BACKGROUND: The benefits of escalating the dose of donepezil in patients who are
      already receiving long-term treatment with it have not been well evaluated.
      Therefore, an exploratory study to assess the effects of donepezil dose
      escalation in patients with Parkinson's disease with dementia, and specifically
      on patients receiving long-term treatment with donepezil, was performed. METHODS:
      Patients treated with 5-mg/day donepezil for at least 3 months and having a Mini
      Mental State Examination (MMSE) score between 10 and 26 were included in this
      study. Donepezil dosage was then increased to 10 mg/day for 12 weeks. The outcome
      measures were a modified form of the Neuropsychiatric Inventory (NPI) with an
      extra domain for additional evaluation of fluctuation in cognitive functions (NPI
      11) and the MMSE. RESULTS: Of the nine patients enrolled, two withdrew because of
      nausea and inability to be assessed on the predetermined date; this left seven
      participants (four men and three women) with a mean age of 74.6 +/- 6.9 years, a
      mean period of Parkinson's disease of 11.7 +/- 7.5 years, and median donepezil
      use of 7 months (range: 3-56 months). At baseline, the mean total NPI-11 and mean
      MMSE scores were 18.3 +/- 5.6 points and 21.3 +/- 5.3 points, respectively. At
      week 12, they improved by 8.3 points (P < 0.01) and 3.0 points (P = 0.08),
      respectively, from the baseline. The NPI symptom domains that improved by 1 or
      more points were hallucination (1.3 points), depression (1.0 points), anxiety
      (1.6 points), and aberrant motor behaviour (1.7 points). None of the patients
      withdrew because of worsening of parkinsonism. CONCLUSIONS: The present results
      suggest that treatment with dose escalation of donepezil from 5 mg/day to 10
      mg/day may be therapeutically useful for patients with Parkinson's disease with
      dementia who have taken donepezil 5 mg/day in the long term.

PMID- 24661499
TI  - Comparative effectiveness of implementation of a nursing-driven protocol in
      reducing bronchodilator utilization for hospitalized children with bronchiolitis.
AB  - OBJECTIVE: The goal of our study was to determine whether the administration of
      bronchodilators is affected by implementation of a nursing-driven protocol in the
      care of children hospitalized with bronchiolitis. METHODS: We included children
      less than 2 years old, hospitalized with bronchiolitis, but without chronic lung
      problems, immunodeficiencies or congenital heart disease in the 1-year periods
      before, during and after implementation of a nursing-driven bronchiolitis
      protocol. The protocol is based on nursing assessments of respiratory status
      prior to initiation and continuation of bronchodilator therapy. Utilization rates
      of bronchodilators were compared with respect to implementation of the nursing
      driven protocol using Chi-square, analysis of variance, and regression analysis
      that is presented as adjusted odds ratio (OR) and 95% confidence interval (95%
      CI) of the OR. RESULTS: Among the 80 children who were hospitalized before, 63
      during and 89 after the implementation of the nursing-driven bronchiolitis
      protocol, 70.0, 60.3, and 29.2%, respectively, received treatment with
      bronchodilators (P < 0.0001). Reduction in the use of bronchodilators in
      association with the implementation of the nursing-driven bronchiolitis protocol
      was also observed after controlling for the child's age and evidence of pneumonia
      (OR 0.68, 95% CI 0.61-0.79). The mean number of bronchodilator doses administered
      among patients in the three groups who received at least one treatment was
      comparable. CONCLUSIONS: Implementation of a nursing-driven bronchiolitis
      protocol was associated with significant reduction in initiation of
      bronchodilator treatments, which suggests a benefit from nursing involvement in
      the promotion of evidence-based recommendations in the management of children
      hospitalized with bronchiolitis.

PMID- 24661501
TI  - Effects of clonal fragmentation on intraspecific competition of a stoloniferous
      floating plant.
AB  - Disturbance is common and can fragment clones of plants. Clonal fragmentation may
      affect the density and growth of ramets so that it could alter intraspecific
      competition. To test this hypothesis, we grew one (low density), five (medium
      density) or nine (high density) parent ramets of the floating invasive plant
      Pistia stratiotes in buckets, and newly produced offspring ramets were either
      severed (with fragmentation) or remained connected to parent ramets (no
      fragmentation). Increasing density reduced biomass of the whole clone (i.e.
      parent ramet plus its offspring ramets), showing intense intraspecific
      competition. Fragmentation decreased biomass of offspring ramets, but increased
      biomass of parent ramets and the whole clone, suggesting significant resource
      translocation from parent to offspring ramets when clones were not fragmented.
      There was no interaction effect of density x fragmentation on biomass of the
      whole clone, and fragmentation did not affect competition intensity index. We
      conclude that clonal fragmentation does not alter intraspecific competition
      between clones of P. stratiotes, but increases biomass production of the whole
      clone. Thus, fragmentation may contribute to its interspecific competitive
      ability and invasiveness, and intentional fragmentation should not be recommended
      as a measure to stop the rapid growth of this invasive species. 

PMID- 24661500
TI  - The role of sex hormones and the tissue environment in immune protection against
      HIV in the female reproductive tract.
AB  - Despite extensive studies of the mucosal immune system in the female reproductive
      tract (FRT) and its regulation by sex hormones, relatively little attention has
      been paid to the tissue environment in the FRT that regulates immune cell
      function. Consisting of secretions from epithelial cells (EC), stromal
      fibroblasts, and immune cells in tissues from the upper (Fallopian tubes, uterus,
      and endocervix) and lower (ectocervix and vagina) tracts, each tissue compartment
      is unique and precisely regulates immune cells to optimize conditions for
      successful pregnancy and protection against sexually transmitted diseases
      including HIV. Our goal in this review is to focus on the mucosal (tissue)
      environment in the upper and lower FRT. Specifically, this review will identify
      the contributions of EC and fibroblasts to the tissue environment and examine the
      impact of this environment on HIV-target cells. Much remains to be learned about
      the complex interactions with the tissue environment at different sites in the
      FRT and the ways in which they are regulated by sex hormones and chemical
      contraceptives. Awareness of the involvement of the tissue environment in
      determining immune cell function and HIV acquisition is crucial for understanding
      the mechanisms that lead to HIV prevention, acquisition, and the development of
      new therapeutic modalities of immune protection. 

PMID- 24661502
TI  - A pathway to empowerment: evaluating a cancer education and support programme in
      New Zealand.
AB  - Support programmes often benefit cancer patients and their families. This study
      evaluates how the Living Well Cancer Education Programme (LWCEP), from the Cancer
      Society of New Zealand, meets the needs of its clients. A purposeful sample of 21
      participants representing the normal range of demographic characteristics (age,
      gender, diagnosis and geographical location) for the programme, participated in
      semi-structured interviews. Demographic data were subjected to a frequency
      analysis. Main data were collected and analysed using a constructivist grounded
      theory approach regarding the experiences of the participants with being on the
      programme and recommendations for future development. Of the 21 participants, 14
      were cancer patients (eight women and six men) and seven were support people
      (five women and two men). The LWCEP was described as a safe, supportive and
      stimulating environment, provided a powerful sense of belonging, empowered
      participants to gain perspective, enhance their confidence and communication
      skills and make increasingly informed choices. Consistent with a previous
      evaluation focussing on the facilitators of the LWCEP, there was a strong desire
      for better promotion of the programme to the wider community, establishment of a
      better referral pathway and the potential to offer two separate programmes
      depending on the stage of a patient's journey. 

PMID- 24661504
TI  - The Ycf54 protein is part of the membrane component of Mg-protoporphyrin IX
      monomethyl ester cyclase from barley (Hordeum vulgare L.).
AB  - The biosynthesis of chlorophyll has been demonstrated to require an extensive set
      of enzymes, the initial stages of which are shared with the synthesis of heme. Of
      these enzymes, the most enigmatic is the Mg-protoporphyrin IX monomethyl ester
      cyclase (EC 1.14.13.81). This enzyme requires components found associated with
      the plastid membrane and the plastid soluble fraction. One of the components,
      XanL, is found associated with the membrane and another protein, Ycf54, has
      recently been identified based upon association with XanL. This study describes a
      deeper analysis of the role of Ycf54 in the enzyme and the localization of the
      protein in barley plastids. The results clearly demonstrate a strong association
      of Ycf54 with XanL, absence of Ycf54 from soluble fractions necessary for
      activity and more evidence for a third membrane localized component of the
      enzyme.

PMID- 24661503
TI  - A systematic review of special events to promote breast, cervical and colorectal
      cancer screening in the United States.
AB  - BACKGROUND: Special events are common community-based strategies for health
      promotion. This paper presents findings from a systematic literature review on
      the impact of special events to promote breast, cervical or colorectal cancer
      education and screening. METHODS: Articles in English that focused on special
      events involving breast, cervical, and/or colorectal cancer conducted in the U.S.
      and published between January 1990 and December 2011 were identified from seven
      databases: Ovid, Web of Science, CINAHL, PsycINFO, Sociological Abstract,
      Cochrane Libraries, and EconLit. Study inclusion and data extraction were
      independently validated by two researchers. RESULTS: Of the 20 articles selected
      for screening out of 1,409, ten articles on special events reported outcome data.
      Five types of special events were found: health fairs, parties, cultural events,
      special days, and plays. Many focused on breast cancer only, or in combination
      with other cancers. Reach ranged from 50-1732 participants. All special events
      used at least one evidence-based strategy suggested by the Community Guide to
      Preventive Services, such as small media, one-on-one education, and reducing
      structural barriers. For cancer screening as an outcome of the events,
      mammography screening rates ranged from 4.8% to 88%, Pap testing was 3.9%, and
      clinical breast exams ranged from 9.1% to 100%. For colorectal screening, FOBT
      ranged from 29.4% to 76%, and sigmoidoscopy was 100% at one event. Outcome
      measures included intentions to get screened, scheduled appointments, uptake of
      clinical exams, and participation in cancer screening. CONCLUSIONS: Special
      events found in the review varied and used evidence-based strategies. Screening
      data suggest that some special events can lead to increases in cancer screening,
      especially if they provide onsite screening services. However, there is
      insufficient evidence to demonstrate that special events are effective in
      increasing cancer screening. The heterogeneity of populations served, event
      activities, outcome variables assessed, and the reliance on self-report to
      measure screening limit conclusions. This study highlights the need for further
      research to determine the effectiveness of special events to increase cancer
      screening.

PMID- 24661505
TI  - Probabilistic approach for determining Salmonella spp. and L. monocytogenes
      concentration in pork meat from presence/absence microbiological data.
AB  - In the present study, prevalence and concentration of Salmonella spp. and
      Listeria monocytogenes in fresh pork cuts were determined through the analysis of
      twelve lots for one year. Five samples were analyzed at retail and after storage
      at 4 and 12 degrees C up to the end of shelf-life (7 days). Results obtained for
      Salmonella spp. indicated that a total of 15 samples (8.33%) were positive, which
      represents 4 (25%) sampling events positive (i.e. at least one sample was
      positive in at least one of the sampling scenarios). Salmonella was randomly
      distributed and direct correlation with storage time and temperature was not
      obtained. For L. monocytogenes, 26 samples (14.44%) were positive, which
      represents 5 (41.67%) positive sampling lots. For this pathogen, a group of
      samples were only positive at the end of the shelf-life but not immediately after
      purchasing indicating clearly that the contamination was not only heterogeneously
      distributed but also close to the levels of detection, and in all the cases below
      the limit of contamination. As neither Salmonella spp. nor L. monocytogenes was
      enumerated by direct plating (<10 cfu/g) a probabilistic approach basing on
      Binomial and Poisson distributions was subsequently performed to estimate
      microbial concentration from presence/absence data. Estimated concentration
      values were below 40 cfu/kg for both pathogens in more than 80% of the tested
      lots. The data collected in this study add new knowledge on this very important
      and difficult to control segment of the farm-to-fork chain.

PMID- 24661506
TI  - [Seroprevalence of toxoplasmosis in pregnant women in Annaba, Algeria].
AB  - BACKGROUND: The aim of the study was to estimate the seroprevalence and risk
      factors of toxoplasmosis in pregnant women in the department of Annaba, Algeria.
      METHODS: We performed a cross-sectional study with analytical purposes. The study
      was collaboration between the laboratory of Parasitology-Mycology, Faculty of
      Medicine of Annaba and Parasite Biology Department at the Pasteur Institute of
      Algeria. A total of 1028 pregnant women who underwent prenatal diagnosis/visit
      were included over a period of 4 years from January 2006 to December 2009.
      Immunoglobulin G and M were assayed, using the microparticle enzyme method. The
      avidity test was used to determine the date of contamination according to age of
      pregnancy. Search for the parasite was made by inoculation of the placenta and
      cord blood in white mice. The study compared mother-to-child serological profiles
      using Western Blot (WB) IgG and IgM. Direct (not well-cooked meat) and indirect
      (presence of cat, gardening) indicators were recorded to search for parasite
      exposure. RESULTS: Seroprevalence was 47.8 % (95 % CI: 44.8 to 51.0) and the rate
      of active toxoplasmosis was 1.1 % (95 % CI 0.6 to 1.8). According to their immune
      status, this was the first serology for 41 % (CI95 %: 38.0-44.0) of women; 12 %
      (CI95 %: 10.5-14.6) of primiparous women had only one serology test during their
      entire pregnancy. Major risk factors were consumption of poorly-cooked meat and
      exposure to cats. CONCLUSION: Toxoplasmosis during pregnancy is a serious issue
      and an effective prevention program is needed.

PMID- 24661507
TI  - Effect of forage inclusion and particle size in diets of neonatal lambs on
      performance and rumen development.
AB  - A slaughter experiment was conducted to determine the effects of alfalfa particle
      size on rumen morphology and performance of lambs. Twenty-four Balouchi lambs
      aged 21 days (9.1 +/- 1.1 kg) were randomly fed control (diet without alfalfa
      hay; CON) and mixed rations containing 15% finely ground (FINE; 2 mm) and 15%
      coarsely chopped alfalfa hay (LONG; 3 to 4 cm). After a 63 days feeding period,
      nine animals (three per treatment) were slaughtered to obtain ruminal tissue
      samples for morphological analyses. Alfalfa particle size did not affect (p >
      0.05) papillae density, height, width, epithelium depth and surface area. Coarse
      alfalfa decreased the stratum corneum and increased (p < 0.05) muscle depth
      compared with fine and control diets. Neither DNA content and nor RNA
      concentration of rumen tissue was affected by feeding different diets. Forage
      particle size did not affect the blood concentration of glucose, urea nitrogen
      (BUN), beta-hydroxybutyric acid (BHBA) and non-esterified fatty acids (NEFA). Dry
      matter intake and feed conversion ratio were higher for control diet; however,
      there were no significant differences between treatments for average daily gain.
      These data suggest that coarse alfalfa significantly reduces the stratum corneum
      and increases muscularity of rumen wall and tended to better feed conversion
      ratio.

PMID- 24661508
TI  - Animal reactions to oncoming vehicles: a conceptual review.
AB  - Animal-vehicle collisions (AVCs) are a substantial problem in a human-dominated
      world, but little is known about what goes wrong, from the animal's perspective,
      when a collision occurs with an automobile, boat, or aircraft. Our goal is to
      provide insight into reactions of animals to oncoming vehicles when collisions
      might be imminent. Avoiding a collision requires successful vehicle detection,
      threat assessment, and evasive behaviour; failures can occur at any of these
      stages. Vehicle detection seems fairly straightforward in many cases, but depends
      critically on the sensory capabilities of a given species. Sensory mechanisms for
      detection of collisions (looming detectors) may be overwhelmed by vehicle speed.
      Distractions are a likely problem in vehicle detection, but have not been clearly
      demonstrated in any system beyond human pedestrians. Many animals likely perceive
      moving vehicles as non-threatening, and may generally be habituated to their
      presence. Slow or minimal threat assessment is thus a likely failure point in
      many AVCs, but this is not uniformly evident. Animals generally initiate evasive
      behaviour when a collision appears imminent, usually employing some aspect of
      native antipredator behaviour. Across taxa, animals exhibit a variety of
      behaviours when confronted with oncoming vehicles. Among marine mammals, right
      whales Eubalaena spp., manatees Trichechus spp., and dugongs Dugong dugon are
      fairly unresponsive to approaching vehicles, suggesting a problem in threat
      assessment. Others, such as dolphins Delphinidae, assess vehicle approach at
      distance. Little work has been conducted on the behavioural aspects of AVCs
      involving large mammals and automobiles, despite their prevalence. Available
      observations suggest that birds do not usually treat flying aircraft as a major
      threat, often allowing close approach before taking evasive action, as they might
      in response to natural predators. Inappropriate antipredator behaviour (often
      involving immobility) is a major source of AVCs in amphibians and terrestrial
      reptiles. Much behavioural work on AVCs remains to be done across a wide variety
      of taxa. Such work should provide broad phylogenetic generalizations regarding
      AVCs and insights into managing AVCs. 

PMID- 24661509
TI  - Facial nerve compression by the posterior inferior cerebellar artery causing
      facial pain and swelling: a case report.
AB  - INTRODUCTION: We report an unusual case of facial pain and swelling caused by
      compression of the facial and vestibulocochlear cranial nerves due to the
      tortuous course of a branch of the posterior inferior cerebellar artery. Although
      anterior inferior cerebellar artery compression has been well documented in the
      literature, compression caused by the posterior inferior cerebellar artery is
      rare. This case provided a diagnostic dilemma, requiring expertise from a number
      of specialties, and proved to be a learning point to clinicians from a variety of
      backgrounds. We describe the case in detail and discuss the differential
      diagnoses. CASE PRESENTATION: A 57-year-old Caucasian woman with a background of
      mild connective tissue disease presented to our rheumatologist with intermittent
      left-sided facial pain and swelling, accompanied by hearing loss in her left ear.
      An autoimmune screen was negative and a Schirmer's test was normal. Her
      erythrocyte sedimentation rate was 6mm/h (normal range: 1 to 20mm/h) and her
      immunoglobulin G and A levels were mildly elevated. A vascular loop protocol
      magnetic resonance imaging scan showed a loop of her posterior inferior
      cerebellar artery taking a long course around the seventh and eighth cranial
      nerves into the meatus and back, resulting in compression of her seventh and
      eighth cranial nerves. Our patient underwent microvascular decompression, after
      which her symptoms completely resolved. CONCLUSION: Hemifacial spasm is
      characterized by unilateral clonic twitching, although our patient presented with
      more unusual symptoms of pain and swelling. Onset of symptoms is mostly in middle
      age and women are more commonly affected. Differential diagnoses include
      trigeminal neuralgia, temporomandibular joint dysfunction, salivary gland
      pathology and migrainous headache. Botulinum toxin injection is recognized as an
      effective treatment option for primary hemifacial spasm. Microvascular
      decompression is a relatively safe procedure with a high success rate. Although a
      rare pathology, posterior inferior cerebellar artery compression causing facial
      pain, swelling and hearing loss should be considered as a differential diagnosis
      in similar cases.

PMID- 24661510
TI  - [Relationship between Helicobacter pylori infection and histopathological
      features of nodular gastritis in children].
AB  - OBJECTIVE: To study the relationship between Helicobacter pylori (Hp) infection
      and histopathological features of nodular gastritis (NG) in children. METHODS: A
      total of 213 children who had undergone gastroscopy due to upper gastrointestinal
      symptoms were enrolled and were divided into NG and non-NG groups according to
      endoscopic appearance. The histopathological features of gastric mucosa were
      evaluated using the updated Sydney System. The rates of Hp infection, moderate to
      severe inflammation and lymphoid follicles formation of gastric mucosa were
      compared between the two groups. RESULTS: Thirty-eight (17.8%) of the subjects
      were diagnosed with NG. The NG group had significantly increased rates of Hp
      infection (86.8% vs 14.3%; P<0.01), moderate to severe inflammation (81.6% vs
      15.4%; P<0.01) and lymphoid follicles formation of gastric mucosa (52.6% vs
      10.3%; P<0.01) compared with the non-NG group. NG had a high specificity (96.8%)
      and a positive predictive value (86.8%) for the diagnosis of Hp infection. NG was
      observed in 33 (56.9%) of 58 Hp-positive children and in 5 (3.2%) of 155 Hp
      negative children (P<0.01). Hp-positive children had higher rates of moderate to
      severe inflammation (86.2% vs 5.2%, P<0.01) and lymphoid follicles formation of
      gastric mucosa (84.2% vs 14.9% P<0.01) compared with Hp-negative children. There
      were significant differences in Hp colonization, degree of inflammation and
      inflammation activity in gastric tissues between the NG and non-NG groups
      (P<0.01). CONCLUSIONS: NG is a special sign of Hp infection in children, which
      mostly shows moderate to severe inflammation of gastric mucosa, and can be used
      as an endoscopic indicator of Hp infection. Hp eradication therapy should be
      considered in the treatment of NG.

PMID- 24661511
TI  - [Clinical effect of triple therapy combined with Saccharomyces boulardii in the
      treatment of Helicobacter pylori infection in children].
AB  - OBJECTIVE: To evaluate the clinical effect of proton pump inhibitor-based triple
      therapy combined with Saccharomyces boulardii in the treatment of Helicobacter
      pylori (Hp) infection among children in terms of Hp eradication rate and
      incidence of adverse events. METHODS: A prospective randomised controlled study
      was conducted on 240 children with a confirmed diagnosis of Hp infection. These
      patients were randomized into triple therapy (n=120) and probiotics groups
      (n=120). The triple therapy group received amoxicillin [40 mg/(kg.d), Tid],
      clarithromycin [15 mg/(kg.d), Bid] and omeprazole [0.7-0.8 mg/(kg.d), Qd], while
      the probiotics group received Saccharomyces boulardii (250 mg, Bid) in addition
      to triple therapy. The course of treatment was 14 days in both groups. The
      adverse events in subjects were recorded by their parents during treatment. Hp
      eradiation was evaluated by (13)C breath test at 4 weeks after treatment, and the
      eradication rate and incidence of adverse events were compared between the two
      groups. RESULTS: The Hp eradication rates were 75.8% (91/120) in the triple
      therapy group and 85% (102/120) in the probiotics group (P>0.05). Compared with
      the triple therapy group, the probiotics group had nonsignificantly lower
      incidence of nausea, vomiting, and abdominal pain (P>0.05) and significantly
      lower incidence of stomatitis, constipation and diarrhea (P<0.05). CONCLUSIONS:
      Triple therapy combined with Saccharomyces boulardii cannot significantly
      increase Hp eradication rate, but can significantly reduce the incidence of
      stomatitis, constipation, and diarrhea during treatment.

PMID- 24661512
TI  - [Prognostic analysis of children with Henoch-Schonlein purpura treated by
      Helicobacter pylori eradication therapy].
AB  - OBJECTIVE: To investigate the effect of Helicobacter pylori (Hp) eradication
      therapy on prognosis in children with Henoch-Schonlein purpura (HSP). METHODS: A
      total of 153 children with HSP were divided into Hp infection treatment group
      (n=22), Hp infection control group (n=21), and Hp infection-negative group
      (n=110). The Hp infection treatment group received one-week triple therapy for Hp
      eradication in addition to conventional treatment, while the Hp infection control
      group and Hp infection-negative group received conventional treatment. All
      patients were followed up for prognostic evaluation. RESULTS: The response rates
      of the Hp infection treatment, control, and negative groups were 86% (19/22), 90%
      (19/21) and 85% (94/110), respectively (P>0.05). The recurrence rates of HSP in
      the Hp infection treatment, control, and negative groups were 14% (3/22), 24%
      (5/21) and 31% (34/110), respectively (P>0.05). The incidence of Henoch-Schonlein
      purpura nephritis (HSPN) in the Hp infection-negative group (36%, 40/110) and
      control group (33%, 7/21) was significantly higher than that in the Hp infection
      treatment group (5%, 1/22) (P<0.05 for both), but no significant difference in
      the incidence of HSPN was found between the control and negative groups (P>0.05).
      CONCLUSIONS: One-week triple therapy for Hp eradication may be useful to reduce
      the incidence of HSPN in children with HSP infected with Hp.

PMID- 24661513
TI  - [Detection rate of Helicobacter pylori and its clinical significance in children
      with Meckel's diverticulum].
AB  - OBJECTIVE: To determine the detection rate of Helicobacter pylori (Hp) in
      children with Meckel's diverticulum (MD) and its clinical significance among
      children with MD. METHODS: Eighty-one children with MD were divided into two
      groups according to the presence (n=45) or absence (n=36) of digestive
      hemorrhage. The detection rates of Hp in MD tissues and stomach tissues were
      determined by immunohistochemistry. The detection rates of Hp were compared
      between the two groups and between the MD tissues with different clinical
      features in the hemorrhage group. RESULTS: The detection rate of Hp in MD tissues
      for the hemorrhage group was 76% (34/45), which was significantly higher than
      that for the non-hemorrhage group (47%, 17/36) (P<0.05). The detection rate of Hp
      in stomach tissues for the hemorrhage group (87%, 39/45) was insignificantly
      higher than that for the non-hemorrhage group (67%, 24/36) (P>0.05). Among
      patients in the bleeding group, the detection rate of Hp in MD tissues showed no
      relationship with age, sex, preoperative hemorrhage frequency, amount of
      hemorrhage, length of MD, basal diameter of MD, and pathological type (P>0.05),
      but was related to location of MD, presence or absence of ulcer, and depth of
      ulcer (P<0.05). For the hemorrhage group, a significant positive correlation was
      found between the detection rates of Hp in MD tissues and stomach tissues
      (P<0.05), as shown by the Spearman correlation analysis. CONCLUSIONS: The
      detection rate of Hp in MD tissues is increased in children with MD complicated
      by digestive hemorrhage. Hp infection may play some role in the hemorrhage
      process among children with MD.

PMID- 24661514
TI  - [Relationship between tight junction proteins and Helicobacter pylori-associated
      gastric diseases].
AB  - Helicobacter pylori (Hp) infection is an important cause of chronic gastritis and
      peptic ulcer, but their pathogenesis is unclear. The role of gastric mucosal
      barrier dysfunction induced by impaired structure and function of tight junction
      in the pathogenesis of Hp-associated gastric diseases has received considerable
      attention in recent years. Tight junction is composed of a variety of proteins
      and molecules, including 3 integral membrane proteins (occludin, claudins, and
      junctional adhesion molecules) and a cytoplasmic protein (zonula occludens). This
      paper mainly describes the composition and function of various tight junction
      proteins, changes in tight junction protein function induced by Hp infection and
      their relationship with the incidence of gastric diseases, and the significance
      of enhancing the tight junction protein function in the prevention and treatment
      of Hp-associated gastric diseases. 

PMID- 24661515
TI  - [Helicobacter pylori infection in children: a new focus].
AB  - Helicobacter pylori (Hp) is a high prevalence of chronic infectious pathogens,
      though not necessarily lead to symptoms, but it can affect the immune system.
      More than of the world's population harbors the bacterium, and most adult Hp
      infection was obtained in childhood. Hp infection is a major cause of peptic
      ulcer, although children rarely suffer from peptic ulcer disease. Hp infection is
      closely related to chronic gastritis, dyspepsia, chronic diarrhea and recurrent
      abdominal pain in children. In recent years, Hp infection may also participate in
      some of non-digestive diseases, such as children's nutritional iron deficiency
      anemia, growth retardation, malnutrition, autoimmune idiopathic thrombocytopenic
      purpura, chronic urticaria, as well as the development of adult atherosclerosis
      related cardiovascular diseases and some nervous system diseases. Hp infection
      can be a lifetime issues of children. Hp infection of children will bring many
      socio-economic problems. In this paper, the correlation of Hp infection in
      stomach and oral cavity, and diagnostic technology, prevention as well as
      treatment strategies for Hp infection will be discussed. 

PMID- 24661516
TI  - [XIAP gene mutation screening in children with hemophagocytic
      lymphohistiocytosis].
AB  - OBJECTIVE: To investigate the prevalence of mutations and sequence variations in
      X-linked inhibitor of apoptosis (XIAP) gene among Chinese pediatric patients with
      hemophagocytic lymphohistiocytosis (HLH). METHODS: Sixty-five children who were
      diagnosed with HLH between January 2009 and December 2012 (case group), as well
      as 70 healthy children (control group), were enrolled in the study. The exons of
      XIAP gene (1-1, 1-2, 2-6) were amplified by PCR and directly sequenced. The
      genotypic and allelic frequencies of single nucleotide polymorphism (SNP) were
      analyzed. RESULTS: None of the HLH patients showed mutations in these exons of
      XIAP gene. Only one nonsynonymous SNP, rs5956583 located in exon 5, was observed,
      but there were no significant differences in the genotypic and allelic
      frequencies of this SNP between the case and control groups (P>0.05).
      CONCLUSIONS: HLH caused by XIAP mutations may be rare in children. SNP rs5956583
      of XIAP gene may have little contribution to the development of childhood HLH.

PMID- 24661517
TI  - [Analysis of mutations in exon 7 of phenylalanine hydroxylase gene among children
      with phenylketonuria in Ningxia, China].
AB  - OBJECTIVE: To investigate the type and frequency of mutations in exon 7 of
      phenylalanine hydroxylase (PAH) gene among children with phenylketonuria (PKU) in
      Ningxia, China and to provide a basis for the genetic diagnosis and prenatal
      diagnosis of PKU in this region. METHODS: Direct sequencing of PCR product was
      performed to analyze the sequences of exon 7 and its flanking introns of 146 PAH
      alleles in 73 children with typical PKU (39 cases of Hui nationality and 34 cases
      of Han nationality) in Ningxia. RESULTS: Six mutations were detected, including
      R243Q (14.4%), R241C (6.8%), IVS7+2T->A (2.7%), L255S (0.7%), G247V (0.7%), and
      G247R (0.7%). The overall frequency of mutations (missense mutation and splice
      site mutation) in exon 7 was 26.0% (38/146). The detection rate of R241C mutation
      was significantly higher in children of Hui nationality than in children of Han
      nationality(10% vs 3%; P<0.05). CONCLUSIONS: In Ningxia, R243Q mutation in exon 7
      of PAH gene is most common in children with PKU, followed by R241C. The frequency
      of R241C mutation in exon 7 of PAH gene varies between children with PKU of Hui
      and Han nationality.

PMID- 24661518
TI  - [Evaluation of psychological fear in children undergoing head-up tilt test].
AB  - OBJECTIVE: To investigate the effects of different tilt angles of head-up tilt
      test (HUTT) and different responses to HUTT on the psychological fear in children
      undergoing the test. METHODS: HUTT was performed on children with unexplained
      syncope or pre-syncope (107 cases: 52 males and 55 females), aged 5.5-17.8 years
      (mean 12.0+/-2.8 years). All subjects were randomly assigned to undergo HUTT at
      an angle of 60 degrees , 70 degrees  or 80 degrees ; the negative cases underwent
      sublingual nitroglycerin-provocation HUTT at the same tilt angle. The Wong-Baker
      Faces Pain Rating Scale was used for self-assessment of psychological fear in
      subjects during HUTT at the end point of the test. RESULTS: The positive rate,
      hemodynamic changes and distribution of response types showed no significant
      differences between children at tilt angles of 60 degrees , 70 degrees  and 80
      degrees  (P>0.05). The greater the tilt angle, the higher the degree of
      psychological fear in children undergoing the test, but there were no significant
      differences between them (P>0.05). The degree of psychological fear in children
      who showed a positive response to HUTT (n=76) was significantly higher than that
      in children who showed a negative response (n=31) (P<0.01). CONCLUSIONS: HUTT can
      cause psychological fear in children undergoing the test, and the degree of
      psychological fear increases in children tested at tilt angles from 60 degrees 
      to 80 degrees , but the differences have no statistical significance. A positive
      response to HUTT can significantly increase the psychological fear in children.

PMID- 24661519
TI  - [Real-time three dimensional echocardiography-based evaluation of left
      ventricular function in children with Kawasaki disease].
AB  - OBJECTIVE: To evaluate the clinical significance of full volume real-time three
      dimensional echocardiography (RT-3DE) in the assessment of general and local
      systolic functions of the left ventricle in children with Kawasaki disease (KD).
      METHODS: A total of 73 KD children (40 with and 33 without coronary artery
      lesions) and 35 healthy control children were recruited. Left ventricular
      ejection fraction (LVEF) was measured by M-mode ultrasound and full volume RT-3DE
      imaging. A left ventricular volume-time curve and a segmental speed-time curve
      were generated. Differences between control subjects and patients with and
      without coronary artery lesions were analyzed. RESULTS: The M-mode ultrasound
      measurements of LVEF in KD patients with coronary artery lesions were
      significantly lower than in KD patients without coronary artery lesions and
      control children (P<0.05), while there was no significant difference between KD
      patients without coronary artery lesions and control children. RT-3DE
      measurements of LVEF were significantly different between the three groups
      analyzed (P<0.05): coronary artery lesion group < no coronary artery lesion group
      < control group. RT-3DE-based segmental ventricular wall analysis revealed that
      Tmsv16-SD and Tmsv12-SD in KD patients with coronary artery lesions were
      significantly higher than other two groups and Tmsv6-SD was also significantly
      higher than in the normal control group (P<0.05) and that Tmsv16-SD in KD
      patients without coronary artery lesions increased significantly compared with
      the normal control group (P<0.05). CONCLUSIONS: RT-3DE can be used in the
      quantitative evaluation of the left ventricular function and therefore has
      significant clinical implications.

PMID- 24661520
TI  - [Efficacy and safety of ribavirin aerosol in children with hand-foot-mouth
      disease].
AB  - OBJECTIVE: To evaluate the efficacy and safety of ribavirin aerosol in children
      with hand-foot-mouth disease (HFMD). METHODS: A randomized, double-blind, placebo
      controlled trial was performed. A total of 119 children with mild HFMD were
      randomly divided into an observed group (n=59) and a control group (n=60). In the
      observed group, ribavirin aerosol was given four times within the first hour,
      followed by once every other hour for the remaining time of the day and day 2;
      from days 3 to 7, it was given 4 times per day, with 2-3 sprays every time, for 7
      days. In the control group, placebo was given in the same way as in the observed
      group. Additionally, both groups used oral antiviral liquid. The scores of
      clinical symptoms including oral ulcer, skin rash, nasal congestion, runny nose,
      sneezing, cough, and fever before and after treatment were recorded to evaluate
      treatment outcomes. Throat swabs were taken before treatment and 5-7 days after
      treatment to measure viral load by RT-PCR and to compare the negative conversion
      rate between the two groups. RESULTS: Fifty-seven patients in the observed group
      and 56 patients in the control group were tested according to the original
      research design. After 5-7 days of treatment, the observed group had a
      significantly higher overall negative conversion rate of enterovirus than the
      control group (P<0.01). The overall marked response rate and overall response
      rate of the observed group were 89% and 89%, respectively, significantly higher
      than those of the control group (29% and 43%). During treatment, there were no
      adverse reactions such as dizziness, vomiting, and notable decreases in
      hemoglobin, white blood cells, and platelets in the two groups. CONCLUSIONS:
      Ribavirin aerosol can be effectively and safely used for treating mild HFMD. With
      low dosage and few adverse reactions, it holds promise for clinical application.

PMID- 24661521
TI  - [Effect of Mycoplasma pneumoniae infection on function of T lymphocytes in
      bronchoalveolar lavage fluid of asthmatic children].
AB  - OBJECTIVE: To investigate the effect of Mycoplasma pneumoniae (MP) infection on
      the function of T lymphocytes in the bronchoalveolar lavage fluid (BALF) of
      asthmatic children in acute and stable periods and the relationship between MP
      infection and asthma. METHODS: Seventy-one hospitalized children (with
      bronchitis, pneumonia, and asthma) were divided into non-MP infection control
      group (group A, pneumonia and bronchitis without MP infection), non-MP infection
      asthma group (group B), and MP infection asthma group (group C). Flow cytometry
      was used to determine CD3(+), CD4(+), and CD8(+) T cell counts and CD4(+)/CD8(+)
      ratio in BALF among all children in acute and stable periods. RESULTS: Compared
      with group A, groups B and C showed significant differences in CD3(+), CD4(+),
      and CD8(+) T cell counts and CD4(+)/CD8(+) ratio (P<0.05) in acute and stable
      periods, had decreased CD3(+) and CD4(+) T cell counts, an increased CD8(+) T
      cell count, and a significantly decreased CD4(+)/CD8(+) ratio (P<0.05) in the
      acute period, and had decreased CD3(+) and CD4(+) T cell counts and CD4(+)/CD8(+)
      ratio and an increased CD8(+) T cell count (P<0.05) in the stable period.
      Compared with group B, group C had significantly decreased CD3(+) and CD4(+) T
      cell counts and CD4(+)/CD8(+) ratio (P<0.05) and a significantly increased CD8(+)
      T cell count (P<0.05) in the acute period and showed no significant differences
      in CD3(+), CD4(+), and CD8(+) T cell counts (P>0.05) and a significant decrease
      in CD4(+)/CD8(+) ratio (P<0.05) in the stable period. CONCLUSIONS: The
      immunological function of T lymphocytes in the airway declines significantly
      among asthmatic children with MP infection in acute and stable periods, leading
      to immue system disorder. MP may be associated with the pathogenesis of asthma.

PMID- 24661522
TI  - [Etiology, clinical features, and diagnosis and treatment of recurrent hemoptysis
      in children].
AB  - OBJECTIVE: To investigate the causes, clinical features, therapy and treatment
      outcomes of recurrent hemoptysis in children and to improve the skills of
      pediatricians in the etiological diagnosis and treatment of recurrent hemoptysis
      in children. METHODS: The clinical, laboratory, and imaging data of 39 children
      with recurrent hemoptysis between January 1996 and February 2013 were collected
      to retrospectively analyze the age of onset, etiology, amount of hemoptysis,
      imaging changes, treatment methods, and follow-up outcomes. RESULTS: In the 39
      children, including idiopathic pulmonary hemosiderosis (16 cases, 41%), pulmonary
      vascular malformation (8 cases, 21%), pulmonary arteriovenous fistula (7 cases,
      18%), bronchiectasis (3 cases, 8%), pulmonary tuberculosis (2 cases, 5%),
      pulmonary cystic fibrosis (2 cases, 5%), and lung tumor (1 case, 3%). The
      contrast-enhanced lung CT scans and pulmonary and bronchial arteriography
      revealed varying degrees of lung imaging changes in 35 cases. Of all cases, 51%
      were classified as degree I, 28% as degree II, and 21% as degree III. All
      children were treated according to the etiology, with the disease controlled.
      During 0.5-5 years of follow-up, 3 patients with idiopathic pulmonary
      hemosiderosis were lost to follow-up, and the other cases did not develop
      hemoptysis again. CONCLUSIONS: Idiopathic pulmonary hemosiderosis is the main
      cause of recurrent hemoptysis in children. Contrast-enhanced lung CT scans and
      pulmonary and bronchial arteriography are important methods for the etiological
      diagnosis of recurrent hemoptysis in children. Treatment methods should be
      selected according to the etiology.

PMID- 24661523
TI  - [Early use of calf pulmonary surfactant in late preterm and full-term infants
      with respiratory distress syndrome: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the efficacy of calf pulmonary surfactant (PS) in the
      treatment of respiratory distress syndrome (RDS) in late preterm and full-term
      infants. METHODS: A randomized controlled trial was designed to evaluate the
      efficacy of calf PS intratracheally given at different times and doses in infants
      with RDS who had a gestational age of >=35 weeks and an oxygenation index (OI) of
      10-20. The subjects were randomly assigned to treatment group 1 (n=58), treatment
      group 2 (n=58), and control group (n=59). Treatment group 1 was given PS (50
      mg/kg) within 6 hours after admission. Treatment group 2 was given PS (70 mg/kg)
      within 6 hours after admission. The control group was not given PS within 6 hours
      after admission and was given PS (50 mg/kg) over 6 hours after admission if
      having no remission by conventional therapy including mechanical ventilation. For
      each group, a second dose of PS (50 mg/kg) was given if no remission was observed
      within 12 hours after the first administration. RESULTS: There were no
      significant differences in mortality between the three groups. Treatment group 2
      had lower hospitalization expense and shorter duration of mechanical ventilation
      compared with treatment group 1, and treatment group 1 had lower hospitalization
      expense and shorter duration of mechanical ventilation compared with the control
      group. The incidence of ventilator-associated pneumonia and length of hospital
      stay in treatment group 2 was lower than those in treatment group 1 and control
      group. Compared with the control group, Treatment groups 1 and 2 showed decreases
      in 2 or more times of PS use, maximum OI, duration of continuous positive airway
      pressure treatment, and incidence of air leak syndrome and pulmonary
      hypertension. CONCLUSIONS: Early use of sufficient PS in late preterm and full
      term infants with RDS can reduce complications, secondary use of PS, duration of
      mechanical ventilation and length of hospital stay, and hospitalization expense.

PMID- 24661524
TI  - [Effects of erythropoietin on neuronal proliferation and apoptosis in neonatal
      rats after infection-induced brain injury].
AB  - OBJECTIVE: To investigate the effects of erythropoietin (EPO) on the neuronal
      proliferation and apoptosis in neonatal rats after infection-induced brain injury
      and the neuroprotective mechanism of EPO in neonatal rats with infection-induced
      brain injury. METHODS: Twenty-six two-day-old neonatal rats were randomly divided
      into 3 groups: control group (intraperitoneally given an equal volume of normal
      saline), lipopolysaccharide (LPS) group (intraperitoneally given LPS 0.6 mg/kg),
      and EPO group (intraperitoneally given LPS 0.6 mg/kg and EPO 5 000 U/kg). These
      groups were injected with respective drugs for 5 consecutive days. Meanwhile,
      each group was intraperitoneally injected with 5-bromo-2'-deoxyuridine (BrdU) (50
      mg/kg) once a day for 5 consecutive days. The expression of BrdU and cleaved
      Caspase-3 in the hippocampal dentate gyrus was detected by immunohistochemistry
      at 24 hours after the last injection. RESULTS: The number of neuronal cells in
      the hippocampal dentate gyrus in the LPS and EPO groups was significantly greater
      than in the control group (P<0.05), but there was no significant difference
      between the LPS and EPO groups. The EPO group had a significantly higher number
      of BrdU-positive cells in the subgranular zone of hippocampal dentate gyrus than
      the LPS group (51+/-9 vs 29+/-6; P<0.05), but a significantly lower number of
      BrdU-positive cells than the control group (51+/-9 vs 67+/-12; P<0.05). The EPO
      group had a significantly lower number of cleaved Caspase-3-positive cells in the
      subgranular zone of hippocampal dentate gyrus than the LPS group (27.9+/-1.5 vs
      34.0+/-1.3; P<0.05), but a significantly higher number of cleaved Caspase-3
      positive cells than the control group (27.9+/-1.5 vs 21.0+/-1.7; P<0.05).
      CONCLUSIONS: EPO can promote hippocampal neuronal proliferation and reduce
      neuronal apoptosis in neonatal rats after infection-induced brain injury.

PMID- 24661525
TI  - [Effect of IGF-1 on long-term anxiety-like behavior in rats after hypoxic
      ischemic brain damage].
AB  - OBJECTIVE: To observe the changes in anxiety-like behavior among rats in the
      recovery stage after hypoxic-ischemic brain damage (HIBD) during the perinatal
      period and to investigate the effect of insulin-like growth factor 1 (IGF-1) on
      the long-term anxiety-like behavior and its action mechanism among rats with
      HIBD. METHODS: Ninety neonatal rats (7 days old) were randomly and equally
      divided into normal control, HIBD, and HIBD+IGF-1 groups. A neonatal rat model of
      HIBD was established by Rice method in the HIBD and HIBD+IGF-1 groups. The rats
      in the HIBD+IGF-1 group were intraperitoneally injected with IGF-1 (0.2 mg/kg)
      immediately after HIBD, and the other two groups were intraperitoneally injected
      with an equal volume of normal saline. The anxiety-like behavior was evaluated by
      elevated plus-maze test on postnatal days 21 and 28. The expression of tyrosine
      hydroxylase (TH) in the substantia nigra was measured by immunohistochemistry on
      postnatal days 14, 21, and 28. RESULTS: On postnatal days 21 and 28, the open-arm
      time (OAT) and percentage of OAT for the HIBD and HIBD+IGF-1 groups were
      significantly lower than those for the normal control group (P<0.05), but there
      were no significant differences between the HIBD and HIBD+IGF-1 groups (P>0.05);
      the percentage of open arm entry showed no significant difference between the
      three groups (P>0.05). On postnatal day 14, there were no significant differences
      in percentage of TH immunostaining-positive area between the three groups
      (P>0.05). On postnatal days 21 and 28, the HIBD and HIBD+IGF-1 groups had
      significantly lower percentages of TH immunostaining-positive area than the
      normal control group (P<0.05), but there was no significant difference between
      the HIBD and HIBD+IGF-1 groups (P>0.05). CONCLUSIONS: HIBD in the perinatal
      period may cause the changes in anxiety-like behavior in adolescent rats, which
      may be related to decreased expression of TH in the substantia nigra. Neonatally
      given IGF-1 cannot improve the long-term anxiety-like behavior in rats after
      HIBD, and it does not affect TH expression in the substantia nigra. IGF-1 may not
      regulate the changes in long-term anxiety-like behavior in adolescent rats.

PMID- 24661526
TI  - [Effect of 1,25-(OH)2D3 on expression of HMGB1 and TLR4 in the lungs of asthmatic
      mice].
AB  - OBJECTIVE: To investigate the effects of 1,25-(OH)(2)D(3) on the airway
      remodeling and expression of high-mobility group box 1 (HMGB1) and Toll-like
      receptor 4 (TLR4) in the lungs among asthmatic mice. METHODS: Thirty female mice
      (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)(2)D(3)
      intervention groups. An asthmatic mouse model was established by intraperitoneal
      injection and aerosol inhalation of ovalbumin. The intervention group was given
      1,25-(OH)(2)D(3) by intraperitoneal injection 0.5 hour before each aerosol
      inhalation, while the control group used normal saline instead. The hematoxylin
      eosin staining was used to observe the mouse airway structural changes. The mRNA
      and protein expression of HMGB1 and TLR4 was measured by RT-PCR and
      immunohistochemistry, respectively. Pearson correlation analysis was performed.
      RESULTS: The asthma group had a significantly increased airway wall thickness
      compared with the control group (P<0.05); the intervention group had a
      significantly lower increase in airway wall thickness than the asthma group
      (P<0.05). The mRNA and protein expression of HMGB1 and TLR4 was significantly
      higher in the asthma group than in the control group (P<0.05); the mRNA and
      protein expression of HMGB1 and TLR4 in the intervention group was significantly
      lower than that in the asthma group, but still higher than that in the control
      group (P<0.05). A positive correlation was found between the protein expression
      of HMGB1 and TLR4 (P<0.01), and so was their mRNA expression (P<0.01).
      CONCLUSIONS: HMGB1 and TLR4 may be involved in asthmatic airway remodeling. 1,25
      (OH)(2)D(3) can reduce the airway remodeling in asthmatic mice, which may be
      related to the downregulation of HMGB1 and TLR4 expression in the lungs of
      asthmatic mice.

PMID- 24661527
TI  - [Application of fiberoptic bronchoscopy in the diagnosis and treatment of
      neonatal respiratory diseases].

PMID- 24661528
TI  - [Clinical analysis of 12 cases of pediatric diffuse large B-cell lymphoma].

PMID- 24661529
TI  - [Fetal atrial flutter in two cases with structurally normal hearts].

PMID- 24661530
TI  - [A case report of glaucoma after topiramate treatment of epilepsy secondary to
      Sturge-Weber syndrome].

PMID- 24661531
TI  - Shear stress-induced mechanotransduction protein deregulation and vasculopathy in
      a mouse model of progeria.
AB  - INTRODUCTION: A mouse model of progeria derived by insertion of the human mutant
      LMNA gene (mLMNA), producing mutant lamin A, shows loss of smooth muscle cells in
      the media of the ascending aorta. We hypothesized that high shear stress, in the
      presence of mutant lamin A, induces this vasculopathy and tried to define the
      molecular and cellular basis for aortic vasculopathy. METHODS: Ascending and
      descending aortas from wild type (WT) and mLMNA+ mice were compared using
      proteomics, Western blots, PCR and immunostaining. To determine whether high
      fluidic shear stress, known to occur in the ascending aorta, contributed to the
      vasculopathy, we exposed descending aortas of mLMNA+ mice, with no apparent
      vasculopathy, to 75 dynes/cm2 shear stress for 30 minutes using a microfluidic
      system. RESULTS: When the mice were one year of age, expression of several
      mechanotransduction proteins in the ascending aorta, including vimentin,
      decreased in mLMNA+ mice but no decrease occurred in the descending aorta. High
      fluidic shear stress produced a significant reduction in vimentin of mLMNA+ mice
      but not in similarly treated WT mice. CONCLUSIONS: The occurrence of mutant lamin
      A and high shear stress correlate with a reduction in the level of
      mechanotransduction proteins in smooth muscle cells of the media. Reduction of
      these proteins may contribute over time to development of vasculopathy in the
      ascending aorta in progeria syndrome.

PMID- 24661532
TI  - In vitro activity of rifaximin against clinical isolates of Escherichia coli and
      other enteropathogenic bacteria isolated from travellers returning to the UK.
AB  - Rifaximin is licensed in the EU and USA for treating travellers' diarrhoea caused
      by non-invasive bacteria. Selection for resistance mechanisms of public health
      significance might occur if these are linked to rifamycin resistance. Rifaximin
      MICs were determined by agar dilution for 90 isolates each of Escherichia coli,
      Shigella spp., nontyphoidal Salmonella enterica, typhoidal S. enterica and
      Campylobacter spp., an additional 60 E. coli with CTX-M ESBLs isolated from
      patients with travellers' diarrhoea, and 30 non-diarrhoeal carbapenemase
      producing E. coli. Comparators were rifampicin, ciprofloxacin, azithromycin,
      trimethoprim/sulfamethoxazole and doxycycline. Isolates with rifaximin MICs>32
      mg/L were screened for arr genes, and critical rpoB regions were sequenced.
      Rifaximin was active at <=32 mg/L against 436/450 (96.9%) diverse
      Enterobacteriaceae, whereas 81/90 (90%) Campylobacter spp. were resistant to
      rifaximin at >=128 mg/L. Rifaximin MICs were >=128 mg/L for two Shigella and five
      MDR E. coli producing NDM (n = 3), OXA-48 (n = 1) or CTX-M-15 (n = 1). Two of the
      five MDR E. coli had plasmids harbouring arr-2 together with bla(NDM), and two
      (one each with bla(NDM) and bla(CTX-M-15)) had His526Asn substitutions in RpoB.
      The rifamycin resistance mechanism remained undefined in one MDR E. coli isolate
      (with bla(OXA-48)) and the two Shigella isolates. Rifaximin showed good in vitro
      activity against diverse Enterobacteriaceae but was largely inactive against
      Campylobacter spp. Rifaximin has potential to co-select MDR E. coli in the gut
      flora, but much stronger associations were seen between ESBL and/or carbapenemase
      production and resistance to alternative treatments for travellers' diarrhoea,
      notably ciprofloxacin and azithromycin.

PMID- 24661533
TI  - Group B meningococcal vaccine: recommendations for UK use.

PMID- 24661534
TI  - [Prevalence and determinants of obesity in children and young people in
      Catalonia, Spain, 2006-2012].
AB  - BACKGROUND AND OBJECTIVE: To estimate the prevalence of obesity and overweight in
      children aged 2 to 14 years in Catalonia, its trends between 2006 and 2010-2012,
      and to evaluate social determinants and lifestyle associated with obesity.
      MATERIAL AND METHODS: A cross-sectional study, using the data from 4,389 surveys
      from Catalonia Health Surveys of the years 2006 and 2010-2012, was conducted.
      Obesity and overweight were determined by World Health Organization criteria.
      Socioeconomic position, parent's education, usual diet and activity, and hours of
      sleep were assessed. RESULTS: The prevalence of obesity and overweight were: 15.4
      and 20.2% in 2010-2012. The prevalence of obesity was higher in boys (15.5%)
      compared to girls (12.8%) (P<.05), and higher in children ranging from 2 to 9
      years old (17.5%) than children aged 10 to 14 years (7.7%) (P<.05). In 2006, the
      prevalence of obesity and overweight were similar to the prevalence in 2010-2012.
      Obesity was more frequent in children with parents with a low socioeconomic
      position and/or a primary or elementary parent's education. CONCLUSIONS: During
      the last 5 years (2006-2012), child obesity and overweight have remained stable
      in Catalonia, yet they are relatively high in Europe. Public health programmes
      against obesity must consider conducting an intersectional action taking social
      determinants and family life styles into account.

PMID- 24661535
TI  - Active video games as a tool to prevent excessive weight gain in adolescents:
      rationale, design and methods of a randomized controlled trial.
AB  - BACKGROUND: Excessive body weight, low physical activity and excessive sedentary
      time in youth are major public health concerns. A new generation of video games,
      the ones that require physical activity to play the games--i.e. active games--may
      be a promising alternative to traditional non-active games to promote physical
      activity and reduce sedentary behaviors in youth. The aim of this manuscript is
      to describe the design of a study evaluating the effects of a family oriented
      active game intervention, incorporating several motivational elements, on
      anthropometrics and health behaviors in adolescents. METHODS/DESIGN: The study is
      a randomized controlled trial (RCT), with non-active gaming adolescents aged 12
      16 years old randomly allocated to a ten month intervention (receiving active
      games, as well as an encouragement to play) or a waiting-list control group
      (receiving active games after the intervention period). Primary outcomes are
      adolescents' measured BMI-SDS (SDS=adjusted for mean standard deviation score),
      waist circumference-SDS, hip circumference and sum of skinfolds. Secondary
      outcomes are adolescents' self-reported time spent playing active and non-active
      games, other sedentary activities and consumption of sugar-sweetened beverages.
      In addition, a process evaluation is conducted, assessing the sustainability of
      the active games, enjoyment, perceived competence, perceived barriers for active
      game play, game context, injuries from active game play, activity replacement and
      intention to continue playing the active games. DISCUSSION: This is the first
      adequately powered RCT including normal weight adolescents, evaluating a
      reasonably long period of provision of and exposure to active games. Next, strong
      elements are the incorporating motivational elements for active game play and a
      comprehensive process evaluation. This trial will provide evidence regarding the
      potential contribution of active games in prevention of excessive weight gain in
      adolescents. TRIAL REGISTRATION: Dutch Trial register NTR3228.

PMID- 24661537
TI  - Temporomandibular joint arthritis as an initial presentation of acute myeloid
      leukemia with myelodysplasia-related changes: a report of an unusual case.
AB  - PURPOSE: Patients with acute myeloid leukemia (AML) often present with fatigue
      and severe pancytopenia. We report the case of a 68-year-old woman with no
      significant medical history who presented with 1 year of progressively worsening
      bilateral temporomandibular joint (TMJ) pain. She was otherwise asymptomatic. A
      computed tomography scan revealed degenerative joint disease in both TMJs.
      Bilateral TMJ replacement was performed. MATERIALS AND METHODS: The excised TMJ
      tissue underwent formalin fixation and decalcification, and routine hematoxylin
      and eosin-stained sections were generated. RESULTS: Immunohistochemical stains
      showed a population of monotonous cells in the marrow space expressing CD33,
      CD43, and myeloperoxidase, confirming the diagnosis of myeloid neoplasm.
      Subsequent bone marrow biopsy with flow cytometry confirmed AML with
      myelodysplasia-related changes. CONCLUSIONS: Adult patients with AML can rarely
      present with musculoskeletal complaints alone, which could delay the diagnosis.
      To our knowledge, this is the first report of AML with myelodysplasia-related
      changes presenting in a patient with TMJ degenerative joint disease that was
      otherwise asymptomatic.

PMID- 24661536
TI  - Inhibition of Methicillin-resistant Staphylococcus aureus-induced cytokines mRNA
      production in human bone marrow derived mesenchymal stem cells by 1,25
      dihydroxyvitamin D3.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the predominant
      cause of bone infection. Toll like receptors (TLRs) are an important segments of
      host response to infection and are expressed by a variety of cells including
      human mesenchymal stem cells (hMSCs). The active form of Vitamin D, 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) has potent immunoregulatory properties, but the
      mechanism remains poorly understood. The genomic action of 1,25(OH)2D3 is
      mediated by vitamin D receptor (VDR), hormone-regulated transcription factor. VDR
      interacts with co-activators and co-repressors are associated with chromatin
      histone modifications and transcriptional regulation. The aim of our study is to
      explore MRSA-induced TLRs-mediated pro-inflammatory cytokines expression in
      hMSCs. Further, we hypothesized that 1,25(OH)2D3 inhibits MRSA-induced cytokines
      synthesis in hMSCs via inhibition of NF-kB transcription factor. Finally, we
      explored the regulatory role of 1,25(OH)2D3 in MRSA-mediated global epigenetic
      histone H3 mark, such as, trimethylated histone H3 lysine 9 (H3K9me3), which is
      linked to gene silencing. RESULTS: Quantitative PCR data revealed that MRSA
      infection predominantly induced expression of TLRs 1, 2, 6, NR4A2, and
      inflammatory cytokines IL-8, IL-6, TNFalpha in hMSCs. MRSA-mediated TLR ligands
      reduced osteoblast differentiation and increased hMSCs proliferation, indicating
      the disrupted multipotency function of hMSCs. Pretreatment of 1,25(OH)2D3
      followed by MRSA co-culture inhibited nuclear translocation of NF-kB-p65, reduced
      expression of NR4A2 and pro-inflammatory cytokines IL-8, IL-6, and TNFalpha in
      hMSCs. Further, NF-kappaB-p65, VDR, and NR4A2 were present in the same nuclear
      protein complex, indicating that VDR is an active part of the nuclear protein
      complexes for transcriptional regulation. Finally, 1,25(OH)2D3 activated VDR,
      restores the global level of H3K9me3, to repress MRSA-stimulated inflammatory
      cytokine IL-8 expression. Pretreatment of 5-dAZA, DNA methylatransferases (Dnmts)
      inhibitor, dramatically re-expresses 1,25(OH)2D3-MRSA-mediated silenced IL-8
      gene. CONCLUSIONS: This data indicates that TLR 1, 2, and 6 can be used as
      markers for localized S. aureus bone infection. 1,25(OH)2D3-VDR may exhibits its
      anti-inflammatory properties in MRSA-stimulated infection by inhibiting nuclear
      translocation of NF-kB-p65 and transcripts of IL-8, IL-6, TNFalpha, and NR4A2 in
      hMSCs. Finally, 1,25(OH)2D3-activated VDR, acting as an epigenetic regulator,
      inhibits synthesis of cytokines in MRSA-stimulated infection by restoring the
      global level of H3K9me3, a histone H3 mark for gene silencing.

PMID- 24661539
TI  - A waste walk through clinical pharmacy: how do the 'seven wastes' of Lean
      techniques apply to the practice of clinical pharmacists.
AB  - AIMS AND OBJECTIVES: This study used a 'Lean' technique, the 'waste walk' to
      evaluate the activities of clinical pharmacists with reference to the seven
      wastes described in 'Lean' including 'defects', 'unnecessary motion',
      'overproduction', 'transport of products or material', 'unnecessary waiting',
      'unnecessary inventory' and 'inappropriate processing'. The objectives of the
      study were to categorise the activities of ward-based clinical pharmacists into
      waste and non-waste, provide detail around what constitutes waste activity and
      quantify the proportion of time attributed to each category. SETTING: This study
      was carried out in a district general hospital in the North West of England.
      METHOD: Staff were observed using work-sampling techniques, to categorise
      activity into waste and non-waste, with waste activities being allocated to each
      of the seven wastes described earlier and subdivided into recurrent themes. KEY
      FINDINGS: Twenty different pharmacists were observed for 1 h on two separate
      occasions. Of 1440 observations, 342 (23.8%) were categorised as waste with
      'defects' and 'unnecessary motion' accounting for the largest proportions of
      waste activity. CONCLUSION: Observation of clinical pharmacists' activities has
      identified that a significant proportion of their time could be categorised as
      'waste'. There are practical steps that could be implemented in order to ensure
      their time is used as productively as possible. Given the challenges facing the
      UK National Health Service, the adoption of 'Lean' techniques provides an
      opportunity to improve quality and productivity while reducing costs.

PMID- 24661538
TI  - Human natural killer cell development in secondary lymphoid tissues.
AB  - For nearly a decade it has been appreciated that critical steps in human natural
      killer (NK) cell development likely occur outside of the bone marrow and
      potentially necessitate distinct microenvironments within extramedullary tissues.
      The latter include the liver and gravid uterus as well as secondary lymphoid
      tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues
      are naturally enriched with NK cell developmental intermediates (NKDI) that span
      a maturation continuum starting from an oligopotent CD34(+)CD45RA(+)
      hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the
      detection of NKDI within the aforementioned tissues, relatively little is known
      about how, why, and when these tissues may be most suited to support NK cell
      maturation and how this process fits in with other components of the human immune
      system. With the discovery of other innate lymphoid subsets whose
      immunophenotypes overlap with those of NKDI, there is also need to revisit and
      potentially re-characterize the basic immunophenotypes of the stages of the human
      NK cell developmental pathway in vivo. In this review, we provide an overview of
      human NK cell development in secondary lymphoid tissues and discuss the many
      questions that remain to be answered in this exciting field. 

PMID- 24661540
TI  - Visualizing variations in organizational safety culture across an inter-hospital
      multifaceted workforce.
AB  - RATIONALE, AIMS AND OBJECTIVES: To develop a reliable and valid questionnaire
      that can distinguish features of organizational culture for patient safety across
      subgroups such as hospitals, professions, management/non-management positions and
      units/wards. METHODS: We developed a Hospital Organizational Culture
      Questionnaire based on a conceptual framework incorporating items from a review
      of existing literature. The questionnaire was administered to hospital staff
      including doctors, nurses, allied health personnel, and administrative staff at
      six public hospitals in Japan. Reliability and validity were assessed through
      exploratory factor analysis, multitrait scaling analysis, Cronbach's alpha
      coefficient and multiple regression analysis using staff-perceived achievement of
      safety as the response variable. Discriminative power across subgroups was
      assessed with radar chart profiling. RESULTS: Of the 3304 hospital staff
      surveyed, 2924 (88.5%) responded. After exploratory factor analysis and
      multitrait analysis, the finalized questionnaire was composed of 24 items in the
      following eight dimensions: improvement orientation, passion for mission,
      professional growth, resource allocation prioritization, inter-sectional
      collaboration, responsibility and authority, teamwork, and information sharing.
      Construct validity and internal consistency of dimensions were confirmed with
      multitrait analysis and Cronbach's alpha coefficients, respectively. Multiple
      regression analysis showed that improvement orientation, passion for mission,
      resource allocation prioritization and information sharing were significantly
      associated with higher achievement in safety practices. Our questionnaire tool
      was able to distinguish features of safety culture among different subgroups.
      CONCLUSIONS: Our questionnaire demonstrated excellent validity and reliability,
      and revealed distinct cultural patterns among different subgroups. Quantitative
      assessment of organizational safety culture with this tool may further the
      understanding of associated characteristics of each subgroup and provide insight
      into organizational readiness for patient safety improvement.

PMID- 24661541
TI  - Magnetotransport study on as-grown and annealed n- and p-type modulation-doped
      GaInNAs/GaAs strained quantum well structures.
AB  - We report the observation of thermal annealing- and nitrogen-induced effects on
      electronic transport properties of as-grown and annealed n- and p-type modulation
      doped Ga1 - xInxNyAs1 - y (x = 0.32, y = 0, 0.009, and 0.012) strained quantum
      well (QW) structures using magnetotransport measurements. Strong and well
      resolved Shubnikov de Haas (SdH) oscillations are observed at magnetic fields as
      low as 3 T and persist to temperatures as high as 20 K, which are used to
      determine effective mass, 2D carrier density, and Fermi energy. The analysis of
      temperature dependence of SdH oscillations revealed that the electron mass
      enhances with increasing nitrogen content. Furthermore, even the current theory
      of dilute nitrides does not predict a change in hole effective mass; nitrogen
      dependency of hole effective mass is found and attributed to both strain- and
      confinement-induced effects on the valence band. Both electron and hole effective
      masses are changed after thermal annealing process. Although all samples were
      doped with the same density, the presence of nitrogen in n-type material gives
      rise to an enhancement in the 2D electron density compared to the 2D hole density
      as a result of enhanced effective mass due to the effect of nitrogen on
      conduction band. Our results reveal that effective mass and 2D carrier density
      can be tailored by nitrogen composition and thermal annealing-induced effects.
      PACS: 72.00.00; 72.15.Gd; 72.80.Ey.

PMID- 24661542
TI  - A qualitative exploration of Pakistan's street children, as a consequence of the
      poverty-disease cycle.
AB  - BACKGROUND: Street children are a global phenomenon, with an estimated population
      of around 150 million across the world. These children include those who work on
      the streets but retain their family contacts, and also those who practically live
      on the streets and have no or limited family contacts. In Pakistan, many children
      are forced to work on the streets due to health-related events occurring at home
      which require children to play a financially productive role from an early stage.
      An explanatory framework adapted from the poverty-disease cycle has been used to
      elaborate these findings. METHODS: This study is a qualitative study, and
      involved 19 in-depth interviews and two key informant interviews, conducted in
      Rawalpindi, Pakistan, from February to May 2013. The data was audio taped and
      transcribed. Key themes were identified and built upon. The respondents were
      contacted through a gatekeeper ex-street child who was a member of the street
      children community. RESULTS: We asked the children to describe their life
      stories. These stories led us to the finding that street children are always
      forced to attain altered social roles because health-related problems, poverty,
      and large family sizes leave them no choice but to enter the workforce and earn
      their way. We also gathered information regarding high-risk practices and
      increased risks of sexual and substance abuse, based on the street children's
      increased exposure. These children face the issue of social exclusion because
      diseases and poverty push them into a life full of risks and hazards; a life
      which also confines their social role in the future. CONCLUSION: The street child
      community in Pakistan is on the rise. These children are excluded from mainstream
      society, and the absence of access to education and vocational skills reduces
      their future opportunities. Keeping in mind the implications of health-related
      events on these children, robust inter-sectoral interventions are required.

PMID- 24661543
TI  - TSH signaling pathways that regulate MCP-1 in human differentiated adipocytes.
AB  - OBJECTIVE: Adipose tissue is an extra-thyroidal thyroid-stimulating hormone (TSH)
      target. Increases in lipolysis and in expression and release of interleukin-6 (IL
      6) occur in TSH-stimulated adipocytes, and levels of circulating free fatty acids
      and IL-6 rise following TSH administration to patients with previous
      thyroidectomy and radioablation for thyroid cancer. Our first objective was to
      compare how TSH stimulates protein kinase A (PKA) and inhibitor of kappaB
      (IkappaB) kinase (IKK)-beta. Our second objective was to investigate whether TSH
      induces other cytokines besides IL-6. METHODS: TSH stimulation of either CHO
      cells expressing human TSH receptor or human abdominal subcutaneous
      differentiated adipocytes. RESULTS: Signaling studies showed TSH increased NADPH
      oxidase activity, and either diphenyleneiodonium (oxidase inhibitor) or N-acetyl
      cysteine (scavenger of reactive oxygen species) reduced IKKbeta phosphorylation.
      Phosphorylation of protein kinase C-delta, an upstream regulator of NADPH
      oxidase, was increased by TSH, and rottlerin (PKCdelta inhibitor) reduced TSH
      stimulated IKKbeta phosphorylation. TSH upregulated monocyte chemoattractant
      protein-1 (MCP-1) mRNA expression and the release of MCP-1 protein in human
      abdominal differentiated adipocytes. H89 (PKA inhibitor) and sc-514 (IKKbeta
      inhibitor) each blocked TSH-stimulated MCP-1 mRNA expression and protein release,
      suggesting PKA and IKKbeta participate in this pathway. CONCLUSIONS: These data
      provide new information about TSH signaling in human differentiated adipocytes,
      and add to the evidence that TSH is a pro-inflammatory stimulus of adipocytes.

PMID- 24661544
TI  - Analysis of melanoma-related microRNAs expression during the spontaneous
      regression of cutaneous melanomas in MeLiM pigs.

PMID- 24661545
TI  - Regulatory T cells: regulators of life.
AB  - Pregnancy still represents one of the most fascinating paradoxical phenomena in
      science. Immediately after conception, the maternal immune system is challenged
      by the presence of foreign paternal antigens in the semen. This triggers
      mechanisms of recognition and tolerance that all together allow the embryo to
      implant and later the fetus to develop. Tolerance mechanisms to maintain
      pregnancy are of special interest as they defy the classical immunology rules.
      Several cell types, soluble factors, and immune regulatory molecules have been
      proposed to contribute to fetal tolerance. Within these, regulatory T cells
      (Treg) are one of the most studied immune cell populations lately. They are
      reportedly involved in fetal acceptance. Here, we summarize several aspects of
      Treg biology in normal and pathologic pregnancies focusing on Treg frequencies,
      subtypes, antigen specificity, and activity as well as on factors influencing
      Treg generation, recruitment, and function. This review also highlights the
      contribution of fetal Treg in tolerance induction and addresses the role of Treg
      in autoimmune diseases and infections during gestation. Finally, the potential of
      Treg as a predictive marker for the success of assisted reproductive techniques
      and for therapeutic interventions is discussed. 

PMID- 24661546
TI  - Unlike fellows - a review of primate-non-primate associations.
AB  - Throughout many regions of the tropics, non-primate animals - mainly birds and
      mammals - have been observed to follow primate groups and to exploit dropped food
      and flushed prey. The anecdotal nature of most of the numerous reports on these
      primate-non-primate associations (PNPAs) may obscure the biological significance
      of such associations. We review the existing literature and test predictions
      concerning the influence of primate traits (body size, activity patterns, dietary
      strategies, habitat, group size) on the occurrence of PNPAs. Furthermore, we
      examine the influence of non-primates' dietary strategies on the occurrence of
      PNPAs, and the distribution of benefits and costs. We detected a strong signal in
      the geographic distribution of PNPAs, with a larger number of such associations
      in the Neotropics compared to Africa and Asia. Madagascar lacks PNPAs altogether.
      Primate body size, activity patterns, habitat and dietary strategies as well as
      non-primate dietary strategies affect the occurrence of PNPAs, while primate
      group size did not play a role. Benefits are asymmetrically distributed and
      mainly accrue to non-primates. They consist of foraging benefits through the
      consumption of dropped leaves and fruits and flushed prey, and anti-predation
      benefits through eavesdropping on primate alarm calls and vigilance. Where
      quantitative information is available, it has been shown that benefits for non
      primates can be substantial. The majority of PNPAs can thus be categorized as
      cases of commensalism, while mutualism is very rare. Our review provides evidence
      that the ecological function of primates extends beyond their manifold
      interactions with plants, but may remain underestimated. 

PMID- 24661547
TI  - Geographic variation in efficacy of atypical antipsychotics for the acute
      treatment of schizophrenia - an individual patient data meta-analysis.
AB  - Generalizability of efficacy results from medication trials across geographic
      regions is disputed. Geographic differences in factors such as patient
      characteristics, treatment practices and disease definitions might lead to
      differences in effect sizes across regions. This study examined geographic
      variation in efficacy results of schizophrenia trials with atypical
      antipsychotics using individual-patient data meta-analysis. Twenty-two studies
      including in total 5233 patients from three regions (North America, Europe, and
      the rest of the world) were included in the random effects meta-analysis. The
      effect size in North American patients was smaller in terms of mean change from
      baseline and in terms of responders (Hedge's G=0.37, 95% CI 0.28-0.46; OR 1.71,
      95% CI 1.35-2.17) as compared to patients in Europe (Hedge's G=0.56, 95% CI 0.34
      0.79; OR 2.25, 95% CI 1.62-3.12) and the rest of the world (Hedge's G=0.53, 95%
      CI 0.12-0.75; OR 2.61, 95% CI 1.66-4.17). The differences were not statistically
      significant. The observed differences remained when the confounding effect of
      unequal distribution of compounds was controlled for by analyzing separately the
      compounds that were studied across all three regions. Based on these results it
      cannot be excluded that there are differences in efficacy results of atypical
      antipsychotics trials across geographic regions. The observed trend towards
      differential efficacy across geographic regions warrants further examination of
      the determinants of these differences. 

PMID- 24661548
TI  - Comparison of plasma vitamin A and E, copper and zinc levels in free-ranging and
      captive greater flamingos (Phoenicopterus roseus) and their relation to
      pododermatitis.
AB  - Pododermatitis is a worldwide problem in captive flamingos. Studies in domestic
      poultry showed that nutrition is a possible influencing factor for
      pododermatitis. Vitamin A and E, copper and zinc levels were analysed in two
      different diets (diet 1 = in-house mix and diet 2 = commercial diet) and in
      plasma of captive greater flamingos fed these diets and compared to those of free
      ranging greater flamingos. Results were analysed with respect to type and
      severity of foot lesions of the individuals from the different groups. Juvenile
      and subadult/adult captive flamingos on diet 1 showed various types and
      severities of foot lesions, whereas no foot lesions were found at the time of
      blood sampling in juvenile captive flamingos on diet 2. Juvenile captive
      flamingos on diet 1 had significantly lower plasma zinc levels than juvenile
      captive flamingos on diet 2 and juvenile free-ranging flamingos; data were also
      lower than reference ranges for flamingos, poultry and cranes. There were no
      significant differences in plasma vitamin A, vitamin E, copper or zinc levels
      between animals with different types of foot lesions or with different severity
      scores. Shortly after the change to diet 2 (fed to juvenile captive flamingos
      that did not show any foot lesion), the flooring of the outdoor water pools was
      covered with fine granular sand. Because both factors (nutrition and flooring)
      were changed during the same evaluation period, it cannot be concluded which
      factor contributed in what extent to the reduction of foot lesions. While it is
      assumed that low plasma zinc levels identified in the group of juvenile captive
      flamingos on diet 1 were not directly responsible for foot lesions observed in
      these animals, they may have played a role in altering the skin integrity of the
      feet and predisposing them to pododermatitis.

PMID- 24661549
TI  - Clinical considerations, management and treatment of fever of unknown origin
      caused by urachal cyst: a case report.
AB  - INTRODUCTION: Urachal cysts are rare congenital anomalies that often prompt
      referral to the paediatric general surgeon because of their associated
      complications such as infection, abdominal pain and the young age at
      presentation. In this report we describe a rare case of fever of unknown origin
      caused by an urachal cyst which was successfully treated with incision and
      drainage only. Since the first description of urachal anomalies by Cabriolus in
      1550, few cases have been reported and, until now, only one case of infected
      urachal cyst presenting as fever of unknown origin has been described in the
      literature. Moreover, the spontaneous resolution of an urachal cyst without
      excision is extremely rare. CASE PRESENTATION: We report our experience in the
      management and treatment of an infected urachal cyst that occurred in a 12-year
      old Caucasian girl who presented to our Department of Paediatric Surgery with a
      30-day history of evening fever. The urachal cyst was treated only with incision
      and drainage through a minimally invasive laparoscopic approach. CONCLUSIONS: The
      incision and drainage of an infected urachal cyst is a simple and safe procedure.
      It assures a complete recovery and avoids potential surgical complications
      related to the total excision of the urachal cyst. This report may provide
      important clues regarding the management of this rare anomaly and we emphasise
      the importance for paediatricians, who should consider the possibility that a
      fever of unknown origin can be caused by an urachal cyst, and for surgeons and
      urologists, because it suggests that conservative treatment of this rare anomaly
      should be considered when possible.

PMID- 24661550
TI  - Human decellularized adipose tissue scaffold as a model for breast cancer cell
      growth and drug treatments.
AB  - Human adipose tissue extracellular matrix, derived through decellularization
      processing, has been shown to provide a biomimetic microenvironment for adipose
      tissue regeneration. This study reports the use of human adipose tissue-derived
      extracellular matrix (hDAM) scaffolds as a three-dimensional cell culturing
      system for the investigation of breast cancer growth and drug treatments. The
      hDAM scaffolds have similar extracellular matrix composition to the
      microenvironment of breast tissues. Breast cancer cells were cultured in hDAM
      scaffolds, and cell proliferation, migration, morphology, and drug responses were
      investigated. The growth profiles of multiple breast cancer cell lines cultured
      in hDAM scaffolds differed from the growth of those cultured on two-dimensional
      surfaces and more closely resembled the growth of xenografts. hDAM-cultured
      breast cancer cells also differed from those cultured on two-dimensional surfaces
      in terms of cell morphology, migration, expression of adhesion molecules, and
      sensitivity to drug treatment. Our results demonstrated that the hDAM system
      provides breast cancer cells with a biomimetic microenvironment in vitro that
      more closely mimics the in vivo microenvironment than existing two-dimensional
      and Matrigel three-dimensional cultures do, and thus can provide vital
      information for the characterization of cancer cells and screening of cancer
      therapeutics.

PMID- 24661551
TI  - Strain-dependent modulation of macrophage polarization within scaffolds.
AB  - Implanted synthetic substrates for the regeneration of cardiovascular tissues are
      exposed to mechanical forces that induce local deformation. Circulating
      inflammatory cells, actively participating in the healing process, will be
      subjected to strain once recruited. We investigated the effect of deformation on
      human peripheral blood mononuclear cells (hPBMCs) adherent onto a scaffold, with
      respect to macrophage polarization towards an inflammatory (M1) and reparative
      (M2) phenotype and to early tissue formation. HPBMCs were seeded onto poly
      epsilon-caprolactone bisurea strips and subjected to 0%, 7% and 12% cyclic strain
      for up to one week. After 1 day, cells subjected to 7% deformation showed
      upregulated expression of pro and anti-inflammatory chemokines, such as MCP-1 and
      IL10. Immunostaining revealed presence of inflammatory macrophages in all groups,
      while immunoregulatory macrophages were detected mainly in the 0 and 7% groups
      and increased significantly over time. Biochemical assays indicated deposition of
      sulphated glycosaminoglycans and collagen after 7 days in both strained and
      unstrained samples. These results suggest that 7% cyclic strain applied to hPBMCs
      adherent on a scaffold modulates their polarization towards reparative
      macrophages and allows for early synthesis of extracellular matrix components,
      required to promote further cell adhesion and proliferation and to bind
      immunoregulatory cytokines. 

PMID- 24661553
TI  - Counterion-enhanced cyanine dye loading into lipid nano-droplets for single
      particle tracking in zebrafish.
AB  - Superior brightness of fluorescent nanoparticles places them far ahead of the
      classical fluorescent dyes in the field of biological imaging. However, for in
      vivo applications, inorganic nanoparticles, such as quantum dots, are limited due
      to the lack of biodegradability. Nano-emulsions encapsulating high concentrations
      of organic dyes are an attractive alternative, but classical fluorescent dyes are
      inconvenient due to their poor solubility in the oil and their tendency to form
      non-fluorescent aggregates. This problem was solved here for a cationic cyanine
      dye (DiI) by substituting its perchlorate counterion for a bulky and hydrophobic
      tetraphenylborate. This new dye salt, due to its exceptional oil solubility,
      could be loaded at 8 wt% concentration into nano-droplets of controlled size in
      the range 30-90 nm. Our 90 nm droplets, which contained >10,000 cyanine
      molecules, were >100-fold brighter than quantum dots. This extreme brightness
      allowed, for the first time, single-particle tracking in the blood flow of live
      zebrafish embryo, revealing both the slow and fast phases of the cardiac cycle.
      These nano-droplets showed minimal cytotoxicity in cell culture and in the
      zebrafish embryo. The concept of counterion-based dye loading provides a new
      effective route to ultra-bright lipid nanoparticles, which enables tracking
      single particles in live animals, a new dimension of in vivo imaging.

PMID- 24661552
TI  - Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes
      with and without RGD-tagging.
AB  - Steric stabilization of cationic liposome-DNA (CL-DNA) complexes is required for
      in vivo applications such as gene therapy. PEGylation (PEG: poly(ethylene
      glycol)) of CL-DNA complexes by addition of PEG2000-lipids yields sterically
      stabilized nanoparticles but strongly reduces their gene delivery efficacy.
      PEGylation-induced weakening of the electrostatic binding of CL-DNA nanoparticles
      to cells (leading to reduced uptake) has been considered as a possible cause, but
      experimental results have been ambiguous. Using quantitative live-cell imaging in
      vitro, we have investigated cell attachment and uptake of PEGylated CL-DNA
      nanoparticles with and without a custom synthesized RGD-peptide grafted to the
      distal ends of PEG2000-lipids. The RGD-tagged nanoparticles exhibit strongly
      increased cellular attachment as well as uptake compared to nanoparticles without
      grafted peptide. Transfection efficiency of RGD-tagged PEGylated CL-DNA NPs
      increases by about an order of magnitude between NPs with low and high membrane
      charge density (sigmaM; the average charge per unit area of the membrane;
      controlled by the molar ratio of cationic to neutral lipid), even though imaging
      data show that uptake of RGD-tagged particles is only slightly enhanced by high
      sigmaM. This suggests that endosomal escape and, as a result, transfection
      efficiency of RGD-tagged NPs is facilitated by high sigmaM. We present a model
      describing the interactions between PEGylated CL-DNA nanoparticles and the
      anionic cell membrane which shows how the PEG grafting density and membrane
      charge density affect adhesion of nanoparticles to the cell surface.

PMID- 24661554
TI  - Renal molecular mechanisms underlying altered Na+ handling and genesis of
      hypertension during adulthood in prenatally undernourished rats.
AB  - In the present study, we investigated the development of hypertension in
      prenatally undernourished adult rats, including the mechanisms that culminate in
      dysfunctions of molecular signalling in the kidney. Dams were fed a low-protein
      multideficient diet throughout gestation with or without alpha-tocopherol during
      lactation. The time course of hypertension development followed in male offspring
      was correlated with alterations in proximal tubule Na+-ATPase activity,
      expression of angiotensin II (Ang II) receptors, and activity of protein kinases
      C and A. After the establishment of hypertension, Ang II levels, cyclo-oxygenase
      2 (COX-2) and NADPH oxidase subunit expression, lipid peroxidation and macrophage
      infiltration were examined in renal tissue. Lipid peroxidation in undernourished
      rats, which was very intense at 60 d, decreased at 90 d and returned to control
      values by 150 d. During the prehypertensive phase, prenatally undernourished rats
      exhibited elevated renal Na+-ATPase activity, type 2 Ang II receptor down
      regulation and altered protein kinase A:protein kinase C ratio. Stable late
      hypertension coexisted with highly elevated levels of Ang II-positive cells in
      the cortical tubulointerstitium, enhanced increase in the expression of p47phox
      (NADPH oxidase regulatory subunit), marked down-regulation of COX-2 expression,
      expanded plasma volume and decreased creatinine clearance. These alterations were
      reduced when the dams were given alpha-tocopherol during lactation. The offspring
      of well-nourished dams treated with alpha-tocopherol exhibited most of the
      alterations encountered in the offspring of undernourished dams not treated with
      alpha-tocopherol. Thus, alterations in proximal tubule Na+ transport, subcellular
      signalling pathways and reactive oxygen species handling in renal tissue underpin
      the development of hypertension.

PMID- 24661555
TI  - Multilocus coalescent analyses reveal the demographic history and speciation
      patterns of mouse lemur sister species.
AB  - BACKGROUND: Debate continues as to whether allopatric speciation or peripatric
      speciation through a founder effect is the predominant force driving evolution in
      vertebrates. The mouse lemurs of Madagascar are a system in which evolution has
      generated a large number of species over a relatively recent time frame. Here, we
      examine speciation patterns in a pair of sister species of mouse lemur,
      Microcebus murinus and M. griseorufus. These two species have ranges that are
      disparately proportioned in size, with M. murinus showing a much more extensive
      range that marginally overlaps that of M. griseorufus. Given that these two
      species are sister taxa, the asymmetric but overlapping geographic ranges are
      consistent with a model of peripatric speciation. To test this hypothesis, we
      analyze DNA sequence data from four molecular markers using coalescent methods.
      If the peripatric speciation model is supported, we predict substantially greater
      genetic diversity in M. murinus, relative to M. griseorufus. Further, we expect a
      larger effective population size in M. murinus and in the common ancestor of the
      two species than in M. griseorufus, with a concomitant decrease in gene
      tree/species tree incongruence in the latter and weak signs of demographic
      expansion in M. murinus. RESULTS: Our results reject a model of peripatric
      divergence. Coalescent effective population size estimates were similar for both
      extant species and larger than that estimated for their most recent common
      ancestor. Gene tree results show similar levels of incomplete lineage sorting
      within species with respect to the species tree, and locus-specific estimates of
      genetic diversity are concordant for both species. Multilocus demographic
      analyses suggest range expansions for M. murinus, with this species also
      experiencing more recent population declines over the past 160 thousand years.
      CONCLUSIONS: Results suggest that speciation occurred in allopatry from a common
      ancestor narrowly distributed throughout southwest Madagascar, with subsequent
      range expansion for M. murinus. Population decline in M. murinus is likely
      related to patterns of climate change in Madagascar throughout the Pleistocene,
      potentially exacerbated by continual anthropogenic perturbation. Genome-level
      data are needed to quantify the role of niche specialization and adaptation in
      shaping the current ranges of these species.

PMID- 24661556
TI  - Unbiased analysis by high throughput sequencing of the viral diversity in fetal
      bovine serum and trypsin used in cell culture.
AB  - Fetal bovine serum (FBS) and trypsin are reagents used in cell culture and have
      been the source of viral contamination of pharmaceutical products. We performed
      high throughput sequencing (HTS) of two pools of commercial batches of FBS and
      three commercial batches of trypsin. Taxonomies were assigned by comparing
      sequences of contigs and singletons to the entire NCBI nucleic acid and protein
      databases. The same major viral species were evidenced between batches of a given
      reagent but the proportion of viral reads among total reads varied markedly
      between samples (from 0.002% to 22.7%). In FBS, the sequences found were mainly
      from bovine viral diarrhea virus (BVDV) 1 to 3 and bovine parvovirus 3 (BPV3).
      The BVDV sequences derived from FBS showed only minor discrepancies with primers
      generally used for the screening of BVDV. Viral sequences in trypsin were mainly
      from porcine circovirus type 2. Other known viral sequences at lower read counts
      and potential new viral species (bovine parvovirus and bovine pegivirus) were
      evidenced. The load of some known and new viruses detected by HTS could be
      quantified by qPCR. Results of HTS provide a framework for evaluating the
      pertinence of control measures including the design of PCRs, bioassays and
      inactivation procedures. 

PMID- 24661557
TI  - Gram-negative bacteremia: which empirical antibiotic therapy?
AB  - PURPOSE: Given the increasing frequency of cefotaxime-resistant strains, third
      generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be
      recommended any longer as empirical antibiotic therapy for community-acquired
      Gram-negative bacteremia (CA-GNB). PATIENTS AND METHODS: We conducted a
      multicenter prospective descriptive study including patients with CA-GNB.
      RESULTS: Two hundred and nineteen patients were included. Escherichia coli and
      Pseudomonas aeruginosa were the most frequently isolated species in 63% (n=138)
      and 11% (n=24) of the cases, respectively. The prevalence of cefotaxime
      resistance reached 18% (n=39) mostly due to intrinsic resistance (27 cases, 12%).
      The presence of invasive material (P<0.001), the origin of the patient (Paris
      region or West of France) (P=0.006), and home health care (P<0.001) were
      variables predicting resistant GNB. The negative predictive value for resistance
      in patients with invasive material coming from the West of France, or without
      invasive material and with home health care was 94%. The positive predictive
      value for patients with invasive material living in Paris, or without invasive
      material and with home health care only reached 58 and 54%, respectively.
      CONCLUSIONS: Using 3GC for CA-GNB due to cefotaxime-resistant strains was
      relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our
      study highlights the role of local epidemiology; before any changes to first-line
      antibiotic therapy, local epidemiological data should be taken into account.

PMID- 24661558
TI  - Spatial modelling and mapping of female genital mutilation in Kenya.
AB  - BACKGROUND: Female genital mutilation/cutting (FGM/C) is still prevalent in
      several communities in Kenya and other areas in Africa, as well as being
      practiced by some migrants from African countries living in other parts of the
      world. This study aimed at detecting clustering of FGM/C in Kenya, and
      identifying those areas within the country where women still intend to continue
      the practice. A broader goal of the study was to identify geographical areas
      where the practice continues unabated and where broad intervention strategies
      need to be introduced. METHODS: The prevalence of FGM/C was investigated using
      the 2008 Kenya Demographic and Health Survey (KDHS) data. The 2008 KDHS used a
      multistage stratified random sampling plan to select women of reproductive age
      (15-49 years) and asked questions concerning their FGM/C status and their support
      for the continuation of FGM/C. A spatial scan statistical analysis was carried
      out using SaTScanTM to test for statistically significant clustering of the
      practice of FGM/C in the country. The risk of FGM/C was also modelled and mapped
      using a hierarchical spatial model under the Integrated Nested Laplace
      approximation approach using the INLA library in R. RESULTS: The prevalence of
      FGM/C stood at 28.2% and an estimated 10.3% of the women interviewed indicated
      that they supported the continuation of FGM. On the basis of the Deviance
      Information Criterion (DIC), hierarchical spatial models with spatially
      structured random effects were found to best fit the data for both response
      variables considered. Age, region, rural-urban classification, education, marital
      status, religion, socioeconomic status and media exposure were found to be
      significantly associated with FGM/C. The current FGM/C status of a woman was also
      a significant predictor of support for the continuation of FGM/C. Spatial scan
      statistics confirm FGM clusters in the North-Eastern and South-Western regions of
      Kenya (p<0.001). CONCLUSION: This suggests that the fight against FGM/C in Kenya
      is not yet over. There are still deep cultural and religious beliefs to be
      addressed in a bid to eradicate the practice. Interventions by government and
      other stakeholders must address these challenges and target the identified
      clusters.

PMID- 24661559
TI  - New research at the 2014 National Abortion Federation Annual Meeting:
      continuously improving abortion care.

PMID- 24661560
TI  - The development of response surface pathway design to reduce animal numbers in
      toxicity studies.
AB  - BACKGROUND: This study describes the development of Response Surface Pathway
      (RSP) design, assesses its performance and effectiveness in estimating LD50, and
      compares RSP with Up and Down Procedures (UDPs) and Random Walk (RW) design.
      METHODS: A basic 4-level RSP design was used on 36 male ICR mice given
      intraperitoneal doses of Yessotoxin. Simulations were performed to optimise the
      design. A k-adjustment factor was introduced to ensure coverage of the dose
      window and calculate the dose steps. Instead of using equal numbers of mice on
      all levels, the number of mice was increased at each design level. Additionally,
      the binomial outcome variable was changed to multinomial. The performance of the
      RSP designs and a comparison of UDPs and RW were assessed by simulations. The
      optimised 4-level RSP design was used on 24 female NMRI mice given Azaspiracid-1
      intraperitoneally. RESULTS: The in vivo experiment with basic 4-level RSP design
      estimated the LD50 of Yessotoxin to be 463 MUg/kgBW (95% CI: 383-535). By
      inclusion of the k-adjustment factor with equal or increasing numbers of mice on
      increasing dose levels, the estimate changed to 481 MUg/kgBW (95% CI: 362-566)
      and 447 MUg/kgBW (95% CI: 378-504 MUg/kgBW), respectively. The optimised 4-level
      RSP estimated the LD50 to be 473 MUg/kgBW (95% CI: 442-517). A similar increase
      in power was demonstrated using the optimised RSP design on real Azaspiracid-1
      data. The simulations showed that the inclusion of the k-adjustment factor,
      reduction in sample size by increasing the number of mice on higher design levels
      and incorporation of a multinomial outcome gave estimates of the LD50 that were
      as good as those with the basic RSP design. Furthermore, optimised RSP design
      performed on just three levels reduced the number of animals from 36 to 15
      without loss of information, when compared with the 4-level designs. Simulated
      comparison of the RSP design with UDPs and RW design demonstrated the superiority
      of RSP. CONCLUSION: Optimised RSP design reduces the number of animals needed.
      The design converges rapidly on the area of interest and is at least as efficient
      as both the UDPs and RW design.

PMID- 24661561
TI  - Detection of changes in the locus coeruleus in patients with mild cognitive
      impairment and Alzheimer's disease: high-resolution fast spin-echo T1-weighted
      imaging.
AB  - AIM: Neuronal degeneration in the locus coeruleus occurs in the early phase of
      Alzheimer's disease, similar to mild cognitive impairment. The locus coeruleus
      produces norepinephrine, a deficiency of which causes both memory disturbance and
      psychological symptoms. Thus, we evaluated signal alterations in the locus
      coeruleus of patients with Alzheimer's disease and mild cognitive impairment
      using a high-resolution fast spin-echo T1-weighted imaging. METHODS: A total of
      22 patients with Alzheimer's disease, 47 patients with mild cognitive impairment
      and 26 healthy controls were prospectively examined by high-resolution fast spin
      echo T1-weighted imaging at 3 Tesla. Signal intensities in the locus coeruleus
      were manually measured and expressed relative to those in the adjacent white
      matter structures as contrast ratios. RESULTS: Locus coeruleus contrast ratios
      were significantly reduced in patient groups with Alzheimer's disease, mild
      cognitive impairment that converted to Alzheimer's disease and mild cognitive
      impairment that did not convert to Alzheimer's disease (1.80-16.09% [median,
      9.30%], 3.45-14.84% [median 6.87%] and 3.01-19.19% [median 7.72%], respectively)
      compared with the healthy control group (6.24-20.94% [median 14.35%]; P <
      0.0001). The sensitivity and specificity for discriminating these diseases were
      85.0% and 69.2%, respectively, which suggests that this measurement can be
      carried out reliably. There was no significant difference in the locus coeruleus
      contrast ratios among the Alzheimer's disease, mild cognitive impairment
      converted and mild cognitive impairment-non-converted groups. CONCLUSIONS: High
      resolution fast spin-echo T1-weighted imaging can show signal attenuation in the
      locus coeruleus of patients with Alzheimer's disease or with mild cognitive
      impairment whose pathology may or may not eventually convert to Alzheimer's
      disease.

PMID- 24661563
TI  - Peri-portal lymphedema in association with an acute adrenal insufficiency: case
      report.
AB  - INTRODUCTION: We report the case of a patient with peri-portal lymphedema in
      association with severe adrenal insufficiency. To the best of our knowledge, this
      association was not previously reported in the literature. Peri-portal lymphedema
      is usually seen in cases such as blunt abdominal trauma, hepatic congestion and
      post-liver transplantation. CASE PRESENTATION: We present the case of a 28-year
      old Indian man who presented to our hospital with adrenal crisis and was treated
      accordingly. Computed tomography of his abdomen showed evidence of peri-portal
      lymphedema (edema) with some free fluid collection. We excluded other causes of
      this pathology and followed the patient's condition after steroid replacement
      therapy. We found no other contributing factors to the patient's peri-portal
      lymphedema apart from the adrenal crisis, which was more consolidated when we
      followed the patient after steroid replacement therapy, during which follow-up
      computed tomography showed complete resolution of the pathology. CONCLUSIONS: We
      conclude following an extensive MEDLINE(r) search that this is the first case to
      be reported for the association between peri-portal lymphedema and adrenal
      insufficiency, after having excluded all other causes of peri-portal lymphedema.
      This signifies reporting of this case as the first one in the medical literature.

PMID- 24661562
TI  - Hmga2 is required for canonical WNT signaling during lung development.
AB  - BACKGROUND: The high-mobility-group (HMG) proteins are the most abundant non
      histone chromatin-associated proteins. HMG proteins are present at high levels in
      various undifferentiated tissues during embryonic development and their levels
      are strongly reduced in the corresponding adult tissues, where they have been
      implicated in maintaining and activating stem/progenitor cells. Here we
      deciphered the role of the high-mobility-group AT-hook protein 2 (HMGA2) during
      lung development by analyzing the lung of Hmga2-deficient mice (Hmga2(-/-)).
      RESULTS: We found that Hmga2 is expressed in the mouse embryonic lung at the
      distal airways. Analysis of Hmga2(-/-) mice showed that Hmga2 is required for
      proper cell proliferation and distal epithelium differentiation during embryonic
      lung development. Hmga2 knockout led to enhanced canonical WNT signaling due to
      an increased expression of secreted WNT glycoproteins Wnt2b, Wnt7b and Wnt11 as
      well as a reduction of the WNT signaling antagonizing proteins GATA-binding
      protein 6 and frizzled homolog 2. Analysis of siRNA-mediated loss-of-function
      experiments in embryonic lung explant culture confirmed the role of Hmga2 as a
      key regulator of distal lung epithelium differentiation and supported the causal
      involvement of enhanced canonical WNT signaling in mediating the effect of Hmga2
      loss-of-fuction. Finally, we found that HMGA2 directly regulates Gata6 and
      thereby modulates Fzd2 expression. CONCLUSIONS: Our results support that Hmga2
      regulates canonical WNT signaling at different points of the pathway. Increased
      expression of the secreted WNT glycoproteins might explain a paracrine effect by
      which Hmga2-knockout enhanced cell proliferation in the mesenchyme of the
      developing lung. In addition, HMGA2-mediated direct regulation of Gata6 is
      crucial for fine-tuning the activity of WNT signaling in the airway epithelium.
      Our results are the starting point for future studies investigating the relevance
      of Hmga2-mediated regulation of WNT signaling in the adult lung within the
      context of proper balance between differentiation and self-renewal of lung
      stem/progenitor cells during lung regeneration in both homeostatic turnover and
      repair after injury.

PMID- 24661564
TI  - Validation of computer-assisted sperm-motility analysis in the amphibian Silurana
      tropicalis.
AB  - We have developed and validated a computer-assisted sperm-motility assessment
      (CASA) method for use with the emerging amphibian model Silurana tropicalis. The
      testicular sperm-activation method was validated by analysing activation
      replicate coefficients of variation, effects of tracking time settings on
      velocity distributions and the relative partitioning of differentially motile
      sperm subpopulations between matched right and left testes. Two major sperm
      subpopulations were identified using multivariate pattern analysis and their
      relative frequencies were consistent between samples from matched right and left
      testes and from randomly drawn subsets of six frogs sampled from the total set of
      16 frogs. The power of this approach for detecting treatment effects targeting
      the hypothalamic-pituitary--gonadal axis was investigated by injecting a group of
      frogs with 100IU human chorionic gonadotrophin (hCG) 2h before sampling and
      comparing their sperm-subpopulation frequencies with non-injected controls. While
      parametric analysis across sperm samples failed to detect treatment effects,
      subpopulation analysis showed that hCG significantly increased the proportion of
      progressive and non-sinuous spermatozoa compared with controls (Chi square=6.40,
      DF=1, P=0.011). This demonstrated the potential value of analysing objectively
      measured sperm behaviour as an endpoint. 

PMID- 24661565
TI  - Generation and preliminary characterization of immortalized cell line derived
      from rat lymphatic capillaries.
AB  - OBJECTIVE: Isolation of rodent endothelial cells from lymphatic capillaries with
      yields that allow extensive functional studies remains challenging due to low
      cell numbers, variable purity, and limited growth potential. The purpose of this
      study was the generation and preliminary characterization of rat lymphatic cell
      line with extended replicative capacity. This cell line is intended for in vitro
      studies of cellular transport in lymphatic endothelium and for in vivo
      experiments in rat animal models. METHODS: We created a novel rat lymphatic
      immortalized cell line, SV40-LEC, using retroviral gene transfer of SV40 large T
      antigen. We confirmed expression of characteristic markers and then examined its
      growth and transport properties. RESULTS: SV40-LECs demonstrated improved
      proliferative capacity, but retained morphological characteristics of lymphatic
      cells and expression of established lymphatic markers. The cells form capillary
      like network in vitro. SV40-LEC monolayer has similar permeability to that of the
      primary initial lymphatics. Paracellular transport in SV40-LECs is limited for
      substances >70 kDa. Barrier properties of the SV40-LECs can be modulated by
      cyclic adenosine monophosphate and histamine, which are known to affect
      microvascular permeability. CONCLUSION: The SV40-LECs provide an excellent tool
      for in vitro studies of properties of lymphatic endothelium, and may be suitable
      for in vivo transplantation studies.

PMID- 24661567
TI  - The Human Placenta Project: placental structure, development, and function in
      real time.
AB  - Despite its crucial role in the health of both the fetus and the pregnant woman,
      the placenta is the least understood human organ. Since a growing body of
      evidence also underscores the importance of placental development in the lifelong
      health of both mother and offspring, this lack of knowledge about placental
      structure and function is particularly concerning. Given modern approaches and
      technologies and the ability to develop new methods, we propose a coordinated
      "Human Placenta Project", with the ultimate goal of understanding human placental
      structure, development, and function in real time. 

PMID- 24661566
TI  - Metabolically healthy obesity and risk of incident type 2 diabetes: a meta
      analysis of prospective cohort studies.
AB  - The risk of type 2 diabetes among obese adults who are metabolically healthy has
      not been established. We systematically searched Medline (1946-August 2013) and
      Embase (1947-August 2013) for prospective studies of type 2 diabetes incidence
      (defined by blood glucose levels or self-report) among metabolically healthy
      obese adults (defined by body mass index [BMI] and normal cardiometabolic
      clustering, insulin profile or risk score) aged >=18 years at baseline. We
      supplemented the analysis with an original effect estimate from the English
      Longitudinal Study of Ageing (ELSA), with metabolically healthy obesity defined
      as BMI >= 30 kg m(-2) and <2 of hypertension, impaired glycaemic control,
      systemic inflammation, adverse high-density lipoprotein cholesterol and adverse
      triglycerides. Estimates from seven published studies and ELSA were pooled using
      random effects meta-analyses (1,770 healthy obese participants; 98 type 2
      diabetes cases). The pooled adjusted relative risk (RR) for incident type 2
      diabetes was 4.03 (95% confidence interval = 2.66-6.09) in healthy obese adults
      and 8.93 (6.86-11.62) in unhealthy obese compared with healthy normal-weight
      adults. Although there was between-study heterogeneity in the size of effects
      (I(2)  = 49.8%; P = 0.03), RR for healthy obesity exceeded one in every study,
      indicating a consistently increased risk across study populations. Metabolically
      healthy obese adults show a substantially increased risk of developing type 2
      diabetes compared with metabolically healthy normal-weight adults. Prospective
      evidence does not indicate that healthy obesity is a harmless condition. 

PMID- 24661568
TI  - Intercellular communication by exosomes in placenta: a possible role in cell
      fusion?
AB  - Exosomes are nanovesicles released from viable cells and have attracted
      increasing interest due to their role in intercellular communication and
      biological functions. More recently exosomes have been shown to be released by
      trophoblasts and to carry molecules involved in placental physiology. This
      involves proteins such as fibronectin, syncytin, Wnt/betacatenin-related
      molecules, galectin-3, and HLA-G, but also bioactive lipids such as the
      immunosuppressive PGE2, the PPARgamma ligand 15d-PGJ2, or microRNAs that appear
      as immunomodulators in pregnancy and are able to confer viral resistance. Exosome
      trafficking within the placental micro-environment potentially links these
      nanovesicles to the organization of the placental interface, fetal tolerance,
      viral protection, and possibly mother-fetus communication. Because of the
      presence of immunocompetent exosomes in breast-milk, they appear as an essential
      component in reproduction. Several aspects of the "exosome pathway" are described
      in the review, from general aspects related to their origin, their
      characteristics and their ability to vectorize material between cells, to more
      specific functions involved in placental physiology such as their putative role
      in triggering cell fusion required for syncytiotrophoblast formation.

PMID- 24661569
TI  - Effects of grain source and marginal change in lucerne hay particle size on feed
      sorting, eating behaviour, chewing activity, and milk production in mid-lactation
      Holstein dairy cows.
AB  - This study investigated the effects of grain source and lucerne hay (LH) particle
      length on eating behaviour, chewing activity, and milk production of lactating
      dairy cows. Eight Holstein dairy cows (175 +/- 21 days in milk) were used in a
      replicated 4 * 4 Latin square design with four 21-days periods. The experiment
      was a 2 * 2 factorial arrangement of treatments with barley grain alone or equal
      blend of barley and maize grains combined with short (15 mm) and long (30 mm) LH.
      Diets were fed ad libitum as total mixed ration with a concentrate to forage
      ratio of 60:40. Interactions between grain source and LH particle length on feed
      particle distributions, sorting index, chewing activity, and milk production were
      minimal. Partially replacing barley grain with maize in the diet overall did not
      change diurnal distributions of particles retained on the sieves of Penn State
      Particle Separator but reduced the proportion of particles on 1.18-sieve and
      increased that of particles on pan (p < 0.05). Grain source did not affect
      sorting index and chewing activity. However, feeding long LH increased (p < 0.01)
      intakes of long particles retained on 19- and 8-mm of sieve, prolonged (p < 0.05)
      eating time, and lowered eating rate (p < 0.05). Interestingly, cows fed with
      long LH ate more coarse particle during critical-early time post feeding (i. e.
      1.5 h), where eating time increased and eating rate decreased (p < 0.05).
      Increasing particle length of dietary LH tended to increase milk fat-to-protein
      ratio (p = 0.08). The results suggested that the increased eating time and
      decreased eating rate as a result of marginally increasing LH particle length
      would be beneficial to alleviate reduction of ruminal pH and milk fat percentage
      following the ingestion of highly fermentable diets.

PMID- 24661570
TI  - Role of alpha-1 antitrypsin in human health and disease.
AB  - Alpha-1 antitrypsin (AAT) deficiency is an under-recognized hereditary disorder
      associated with the premature onset of chronic obstructive pulmonary disease,
      liver cirrhosis in children and adults, and less frequently, relapsing
      panniculitis, systemic vasculitis and other inflammatory, autoimmune and
      neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals
      and has its highest prevalence (1 : 2000-1 : 5000 individuals) in Northern,
      Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000-10
      000. Prevalence is five times lower in Latin American countries and is rare or
      nonexistent in African and Asian individuals. The key to successful diagnosis is
      by measuring serum AAT, followed by the determination of the phenotype or
      genotype if low concentrations are found. Case detection allows implementation of
      genetic counselling and, in selected cases, the application of augmentation
      therapy. Over the past decade, it has been demonstrated that AAT is a broad
      spectrum anti-inflammatory, immunomodulatory, anti-infective and tissue-repair
      molecule. These new capacities are promoting an increasing number of clinical
      studies, new pharmacological formulations, new patent applications and the search
      for alternative sources of AAT (including transgenic and recombinant AAT) to meet
      the expected demand for treating a large number of diseases, inside and outside
      the context of AAT deficiency.

PMID- 24661573
TI  - Transcriptome sequencing of melanocytic nevi and melanomas from Grm1 transgenic
      mice to determine melanoma driver mutations.

PMID- 24661572
TI  - Consuming viscous prey: a novel protein-secreting delivery system in neotropical
      snail-eating snakes.
AB  - BACKGROUND: Efficient venom delivery systems are known to occur only in varanoid
      lizards and advanced colubroidean snakes among squamate reptiles. Although
      components of these venomous systems might have been present in a common
      ancestor, the two lineages independently evolved strikingly different venom gland
      systems. In snakes, venom is produced exclusively by serous glands in the upper
      jaw. Within the colubroidean radiation, lower jaw seromucous infralabial glands
      are known only in two distinct lineages-the basal pareatids and the more advanced
      Neotropical dipsadines known as "goo-eating snakes". Goo-eaters are a highly
      diversified, ecologically specialized clade that feeds exclusively on
      invertebrates (e.g., gastropod molluscs and annelids). Their evolutionary success
      has been attributed to their peculiar feeding strategies, which remain
      surprisingly poorly understood. More specifically, it has long been thought that
      the more derived Dipsadini genera Dipsas and Sibynomorphus use glandular toxins
      secreted by their infralabial glands to extract snails from their shells.
      RESULTS: Here, we report the presence in the tribe Dipsadini of a novel lower jaw
      protein-secreting delivery system effected by a gland that is not functionally
      related to adjacent teeth, but rather opens loosely on the oral epithelium near
      the tip of the mandible, suggesting that its secretion is not injected into the
      prey as a form of envenomation but rather helps control the mucus and assists in
      the ingestion of their highly viscous preys. A similar protein-secreting system
      is also present in the goo-eating genus Geophis and may share the same adaptive
      purpose as that hypothesized for Dipsadini. Our phylogenetic hypothesis suggests
      that the acquisition of a seromucous infralabial gland represents a uniquely
      derived trait of the goo-eating clade that evolved independently twice within the
      group as a functionally complex protein-secreting delivery system. CONCLUSIONS:
      The acquisition by snail-eating snakes of such a complex protein-secreting system
      suggests that the secretion from the hypertrophied infralabial glands of goo
      eating snakes may have a fundamental role in mucus control and prey transport
      rather than envenomation of prey. Evolution of a functional secretory system that
      combines a solution for mucus control and transport of viscous preys is here
      thought to underlie the successful radiation of goo-eating snakes.

PMID- 24661574
TI  - FeSb2-Al2O3-C nanocomposite anodes for lithium-ion batteries.
AB  - FeSb2-Al2O3-C nanocomposite synthesized by ambient-temperature high-energy
      mechanical milling (HEMM) of Sb2O3, Fe, Al, and C has been investigated as an
      anode material for lithium-ion batteries. The FeSb2-Al2O3-C nanocomposites are
      characterized with X-ray diffraction (XRD), X-ray photoelectron spectroscopy
      (XPS), scanning electron microscopy (SEM), and high-resolution transmission
      electron microscopy (HRTEM). The characterization data reveal it to be composed
      of crystalline FeSb2 nanoparticles finely dispersed in an amorphous matrix of
      Al2O3 and carbon. The FeSb2-Al2O3-C nanocomposite exhibits an initial discharge
      (lithiation) capacity of 877 mAh g(-1) and an initial charge (delithiation)
      capacity of 547 mAh g(-1), yielding an initial coulombic efficiency of 62%. The
      extended cycling performance for this composite is far superior to that of the
      intermetallic FeSb2 or a similarly prepared FeSb2-C composite. FeSb2-Al2O3-C
      retains a specific capacity of ~350 mAh g(-1) after 500 lithiation/delithiation
      cycles. 

PMID- 24661571
TI  - Laying a solid foundation for Manhattan--'setting the functional basis for the
      post-GWAS era'.
AB  - Genome-wide association studies (GWAS) have identified more than 8900 genetic
      variants, mainly single-nucleotide polymorphisms (SNPs), associated with hundreds
      of human traits and diseases, which define risk-associated loci. Variants that
      map to coding regions can affect protein sequence, translation rate, and
      alternative splicing, all of which influence protein function. However, the vast
      majority of sequence variants map to non-coding intergenic and intronic regions,
      and it has been much more challenging to assess the functional nature of these
      variants. Recent work annotating the non-coding regions of the genome has
      contributed to post-GWAS studies by facilitating the identification of the
      functional targets of risk-associated loci. Many non-coding genetic variants
      within risk-associated loci alter gene expression by modulating the activity of
      cis-regulatory elements. We review here these recent findings, discuss their
      implication for the post-GWAS era, and relate their importance to the
      interpretation of disease-associated mutations identified through whole-genome
      sequencing. 

PMID- 24661575
TI  - Association among Working Hours, Occupational Stress, and Presenteeism among Wage
      Workers: Results from the Second Korean Working Conditions Survey.
AB  - OBJECTIVES: The purpose of the present study was to identify the association
      between presenteeism and long working hours, shiftwork, and occupational stress
      using representative national survey data on Korean workers. METHODS: We analyzed
      data from the second Korean Working Conditions Survey (KWCS), which was conducted
      in 2010, in which a total of 6,220 wage workers were analyzed. The study
      population included the economically active population aged above 15 years, and
      living in the Republic of Korea. We used the chi-squared test and multivariate
      logistic regression to test the statistical association between presenteeism and
      working hours, shiftwork, and occupational stress. RESULTS: Approximately 19% of
      the workers experienced presenteeism during the previous 12 months. Women had
      higher rates of presenteeism than men. We found a statistically significant dose
      response relationship between working hours and presenteeism. Shift workers had a
      slightly higher rate of presenteeism than non-shift workers, but the difference
      was not statistically significant. Occupational stress, such as high job demand,
      lack of rewards, and inadequate social support, had a significant association
      with presenteeism. CONCLUSIONS: The present study suggests that long working
      hours and occupational stress are significantly related to presenteeism.

PMID- 24661576
TI  - Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium
      animalis subsp. lactis induce bifidogenesis and modulate markers of immune
      function in healthy adults: a double-blind, placebo-controlled, randomised,
      factorial cross-over study.
AB  - Prebiotics, probiotics and synbiotics are dietary ingredients with the potential
      to influence health and mucosal and systemic immune function by altering the
      composition of the gut microbiota. In the present study, a candidate prebiotic
      (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp.
      lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi
      07/d) was given to healthy adults (25-65 years) for 21 d. The aim was to identify
      the effect of the supplements on bowel habits, self-reported mood, composition of
      the gut microbiota, blood lipid concentrations and immune function. XOS
      supplementation increased mean bowel movements per d (P= 0.009), but did not
      alter the symptoms of bloating, abdominal pain or flatulence or the incidence of
      any reported adverse events compared with maltodextrin supplementation. XOS
      supplementation significantly increased participant-reported vitality (P= 0.003)
      and happiness (P= 0.034). Lowest reported use of analgesics was observed during
      the XOS+Bi-07 supplementation period (P= 0.004). XOS supplementation
      significantly increased faecal bifidobacterial counts (P= 0.008) and fasting
      plasma HDL concentrations (P= 0.005). Bi-07 supplementation significantly
      increased faecal B. lactis content (P= 0.007), lowered lipopolysaccharide
      stimulated IL-4 secretion in whole-blood cultures (P= 0.035) and salivary IgA
      content (P= 0.040) and increased IL-6 secretion (P= 0.009). XOS supplementation
      resulted in lower expression of CD16/56 on natural killer T cells (P= 0.027) and
      lower IL-10 secretion (P= 0.049), while XOS and Bi-07 supplementation reduced the
      expression of CD19 on B cells (XOS * Bi-07, P= 0.009). The present study
      demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid
      profile and modulate the markers of immune function in healthy adults. The
      provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the
      discrete effects of Bi-07 on the gut microbiota and markers of immune function.

PMID- 24661577
TI  - Relationship between CTX-II and patient characteristics, patient-reported
      outcome, muscle strength, and rehabilitation in patients with a focal cartilage
      lesion of the knee: a prospective exploratory cohort study of 48 patients.
AB  - BACKGROUND: C-telopeptide fragments of type II collagen (CTX-II) are created
      during articular cartilage breakdown and CTX-II is considered useful as a
      biomarker of osteoarthritis. The primary objective of the present study was to
      explore the relationship between urinary CTX-II concentration and patient
      characteristics, patient-reported outcome, muscle strength, and rehabilitation in
      patients with isolated focal knee cartilage lesions. Furthermore, the secondary
      objective was to examine differences in urinary CTX-II concentration between
      patients with focal cartilage lesions and healthy controls. METHODS: 48 patients
      (mean age 33.4 years, standard deviation 9.0) with a focal full-thickness
      (International Cartilage Repair Society grade 3 or 4) cartilage lesion on the
      medial or lateral femoral condyle were included. After baseline assessments, the
      patients completed a 3-month rehabilitation program and 44 patients attended the
      3 month follow-up. Baseline and follow-up assessments consisted of urinary CTX
      II, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and isokinetic
      quadriceps and hamstring muscle strength measurements. CTX-II was also analysed
      in urine samples from 6 healthy individuals, serving as normal controls.
      Correlations were classified as very weak (correlation coefficient [r] < 0.20),
      weak (r = 0.20 - 0.39), moderate (r = 0.40 - 0.59), strong (r = 0.60 - 0.79), and
      very strong (r > 0.80). RESULTS: Except for age and quadriceps strength, no
      significant correlations were found between CTX-II concentrations and baseline
      characteristics, KOOS, or muscle strength. Except for age, all correlations were
      considered as weak or very weak. The patients with a focal cartilage lesion had
      significantly higher mean CTX-II concentration than the healthy control
      individuals both at baseline (p = 0.001) and at follow-up (p = 0.001). The mean
      CTX-II concentration tended to decrease during rehabilitation, but the reduction
      was not significant (p = 0.076). CONCLUSIONS: The current exploratory study
      demonstrated that patients with a focal cartilage lesion of the knee had higher
      concentrations of urinary CTX-II than healthy individuals. In addition, CTX-II
      concentration tended to decrease during rehabilitation. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00885729.

PMID- 24661578
TI  - Comparison of clinical parameters and environmental noise levels between regular
      surgery and piezosurgery for extraction of impacted third molars.
AB  - BACKGROUND/PURPOSE: Impacted third molars can be extracted by regular surgery or
      piezosurgery. The aim of this study was to compare clinical parameters and device
      produced noise levels between regular surgery and piezosurgery for the extraction
      of impacted third molars. METHODS: Twenty patients (18 women and 2 men, 17-29
      years of age) with bilateral symmetrical impacted mandibular or maxillary third
      molars of the same level were included in this randomized crossover clinical
      trial. The 40 impacted third molars were divided into a control group (n = 20),
      in which the third molar was extracted by regular surgery using a high-speed
      handpiece and an elevator, and an experimental group (n = 20), in which the third
      molar was extracted by piezosurgery using a high-speed handpiece and a piezotome.
      The clinical parameters were evaluated by a self-reported questionnaire. The
      noise levels produced by the high-speed handpiece and piezotome were measured and
      compared between the experimental and control groups. RESULTS: Patients in the
      experimental group had a better feeling about tooth extraction and force delivery
      during extraction and less facial swelling than patients in the control group.
      However, there were no significant differences in noise-related disturbance,
      extraction period, degree of facial swelling, pain score, pain duration, any
      noise levels produced by the devices under different circumstances during tooth
      extraction between the control and experimental groups. CONCLUSION: The
      piezosurgery device produced noise levels similar to or lower than those of the
      high-speed drilling device. However, piezosurgery provides advantages of
      increased patient comfort during extraction of impacted third molars.

PMID- 24661579
TI  - Response to: "prevalence of Helicobacter pylori in Lanyu island".

PMID- 24661580
TI  - Impact of periodic selective mebendazole treatment on soil-transmitted helminth
      infections in Cuban schoolchildren.
AB  - OBJECTIVE: To evaluate the impact of periodic selective treatment with 500 mg
      mebendazole on soil-transmitted helminth (STH) infections in Cuban
      schoolchildren. METHODS: We followed up a cohort of 268 STH-positive
      schoolchildren, aged 5-14 years at baseline, at six-month intervals for two years
      and a final follow-up after three years. Kato-Katz stool examination was used to
      detect infections with Ascaris lumbricoides, Trichuris trichiura and hookworm.
      Common risk factors related to STHs were assessed by parental questionnaire.
      RESULTS: A significant reduction in the number of STH infections was obtained
      after three years with the highest reduction for T. trichiura (87.8%) and the
      lowest for hookworm (57.9%). After six months, cure rates (CRs) were 76.9% for A.
      lumbricoides, 67.4% for T. trichiura and 44.4% for hookworm. After two treatment
      rounds, more than 75% of all STH-positive children at baseline were cured, but
      with important differences between STH species (95.2% for A. lumbricoides, 80.5%
      for T. trichiura and 76.5% for hookworm). At the end of the study, these
      cumulative CRs were almost 100% for all three STHs. Risk factors for STHs were
      sex, sanitary disposal and habit of playing in the soil. CONCLUSIONS: Our results
      indicate that periodic selective treatment with 500 mg mebendazole is effective
      in reducing the number of STH infections in Cuban schoolchildren. Although
      important differences were found between helminth species, two rounds of
      treatment appeared sufficient to obtain substantial reductions.

PMID- 24661581
TI  - [Psychopathology of asylum seekers in Europe, trauma and defensive functioning].
AB  - Refugees seeking asylum are a particularly vulnerable population. It has been
      observed that among the most commonly-occurring disorders exhibited in this
      population, there is a high incidence of post-traumatic stress disorder,
      generalized anxiety disorder, and depression. These disorders may be linked to
      the difficult paths that refugees are forced to undertake, as well as to
      different traumatic events which are particularly destructive psychologically
      (deliberate physical, sexual and/or psychological violence, traumatic
      bereavements in the context of war, or social and political instability, socio
      economic, familial or administrative difficulties), which compromise their view
      of their short-term futures. In the face of the weight of these life events, the
      question of the psychological resources of the individual is at the forefront of
      our understanding of mental health and the capacity to adjust to trauma. Our
      study aims to apprehend in a dynamic way, the different strategies used by asylum
      seekers in our western countries to adjust psychologically to traumatic and
      stressful events. The aim of this research is to study the links between mental
      health and anxious and depressive psychopathologies as well as the defensive
      modalities of these subjects. One hundred and twenty adult asylum seekers, living
      in refugee centres in Slovakia, France and Norway have agreed to participate in
      this study. We tried to assess the psychopathological disorders manifesting in
      these populations, notably PTSD, major depression and generalized anxiety
      disorder. Using the DSQ-60 we also tried to establish the links between the
      psychopathologies observed in this population and the defence mechanisms
      employed. Our results reveal that 60% of subjects do indeed suffer from
      psychopathological disorders with an important comorbidity of PTSB and depression
      (64.2%). Furthermore, the seriousness of the symptoms is correlated with less
      adaptive defence mechanisms (a higher incidence of defence mechanisms such as
      acting-out and distorted self-image). The recourse to mechanisms such as
      affiliation, repression and idealization is found to be used less by the study's
      target group. Rather, they tend to resort to defence mechanisms such as
      projection, low self-esteem, withdrawal, acting-out and hypochondria. Our results
      highlight the importance of the affiliation mechanism, which holds the potential
      to facilitate adaptation and resilience in these vulnerable subjects. It could
      also be offered as part of a therapeutic care proposal.

PMID- 24661582
TI  - [Patterns of alcohol consumption in France and their medical and social
      consequences as seen through the family circle and friends and general
      practitioners].
AB  - BACKGROUND: Data on the frequency of high-risk alcohol consumption and its
      medical and social consequences in the French general population remain
      fragmented. Therefore, our aim was two-fold: (i) to assess the prevalence of
      different patterns of alcohol consumption using the AUDIT-C scale, according to
      two different perspectives, i.e., that of family circle members or friends, and
      that of the general practitioners (GPs), and (ii) to examine the prevalence of
      medical and social consequences associated with alcohol consumption profiles.
      METHOD: Data were drawn from two national surveys conducted in 2013.
      Investigators were respectively GPs and family circle members or friends. These
      surveys were respectively representative of GPs (n=1308) and of the general adult
      population (n=1018). RESULTS: The 12-month prevalence rates of harmful or at risk
      alcohol consumption rose respectively to 11.1% in the GPs adult patients and to
      11.9% in the general adult population. The majority of participants with "at
      risk" alcohol consumption presented with significant social and medical
      consequences. Thus, more than seven out of ten participants with chronic at risk
      consumption endorsed significant negative social event potentially associated
      with alcohol like withdrawal of driving licence, getting divorced or separated,
      and losing friends. Over 10% of these participants had liver disease and diabetes
      mellitus, more than 30% increased blood pressure and nearly 50% anxiety disorder
      or major depression. Following adjustments for sociodemographic characteristics
      and alcohol treatment, prevalences of numerous social and medical consequences
      significantly differed between alcohol-dependent participants, chronic at risk
      consumers and episodic at risk consumers. CONCLUSIONS: Our results suggest that
      more than one adult out of ten in France showed during the past year harmful or
      "at risk" alcohol consumption, which appears insufficiently detected and treated.
      In addition, the majority of at risk alcohol consumers already presents with
      serious medical and social consequences. Furthermore, we found that AUDIT-C scale
      can identify different patterns of alcohol consumption, which form a continuum in
      terms of medical and social consequences. Our study indicates the need for
      vigorous education efforts for the public, professionals and policy makers about
      alcohol use disorders, to encourage help-seeking among those who cannot stop
      drinking despite considerable harm to themselves and others, and ideally to
      promote early detection and treatment of individuals with at risk alcohol
      consumption before the development of social and medical consequences and alcohol
      dependence.

PMID- 24661583
TI  - Collaborative retrospective multicentre series of giant intracavernous carotid
      aneurysms.
AB  - Giant intracavernous carotid aneurysms (GICCA) occur with very unusual clinical
      symptoms often resulting from a compressive mechanism that may possibly resolve
      although seldom from a rupture or haemorrhage. In fact, due to their clinical
      presentation their treatment is different from that of the intracranial
      subarachnoid aneurysms. The aim of this study was to analyze the clinical
      symptoms, therapeutic decisions, and the clinical state at 6 months follow up in
      a retrospective consecutive multicentre series of 27 GICCA between 2004 and 2008.
      All the patients in the series were female, mean age 65 years (21 to 82 years). A
      pseudo tumoural cavernous sinus syndrome revealed the disease in 25 patients
      (92.6%), an atypical headache in one patient, and in another patient an
      intraoperative haemorrhage led to the diagnosis. In most of the cases the
      aneurysms were sacciform in shape (89%), with a size between 25 and 30
      millimeters (66.6%) and contained a blood clot due to intrasacular thrombosis
      (57.5%). An occlusion test of the internal carotid artery was performed during
      the diagnostic angiography in 24 cases (88.8%) and good tolerance of occlusion
      was observed in 16 of them. An endovascular procedure was performed in 21
      patients (77.7%): selective coiling of the aneurysm facilitated by stenting or by
      remodeling techniques in 2 cases, whereas internal carotid artery occlusion was
      performed on the 19 other cases. Among these latter patients, 2 of them (10.5%)
      presented with a poor tolerance during the pre-therapeutic carotid occlusion
      test, necessitating a surgical intra-extra cranial by-pass prior to the carotid
      endovascular occlusion. In 1 other case of these 19, the internal carotid
      endovascular occlusion was carried-out in emergency because the aneurysm was
      revealed by a major haemorrhage during the surgical transsphenoidal approach of a
      hypophyseal tumour. No treatment was decided in the remaining 6 cases of the
      series (22.2%). At 6 months follow-up, 18 of the 21 treated patients experienced
      a clinical recovery of their symptoms and 10 of them (50%) had a complete
      clinical recovery. Among the 6 untreated patients, 4 had a partial recovery but
      no complete recovery of oculomotor deficits was observed in this group of
      patients. No clinical worsening was observed in the entire series, neither among
      the treated patients nor among the untreated patients. In conclusion, this study
      underlines the need of a treatment for symptomatic GICCA in order to achieve a
      complete clinical recovery of the symptoms due to intracavernous compression,
      although only partial recovery may be expected from spontaneous evolution.

PMID- 24661584
TI  - Risk of ischemic stroke in patients with ovarian cancer: a nationwide population
      based study.
AB  - BACKGROUND: Cancer patients are at risk of thromboembolism. However, studies
      investigating the relationship between ovarian cancer and ischemic stroke are
      lacking. The objectives of this study were to assess the association between
      ovarian cancer and ischemic stroke, and to determine the predictive risk factors.
      METHODS: Ovarian cancer patients aged 20 years and older without antecedent
      cerebrovascular events and who were followed up for more than 1 year between 1
      January 2003 and 31 December 2011 were recruited from the Taiwan National Health
      Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer
      patients compared with an age- and comorbidity-matched cohort were calculated by
      Cox proportional regression analysis. The difference in cumulative ischemic
      stroke incidence between ovarian cancer patients and the matched cohort was
      analyzed with the Kaplan-Meier method and tested with the log-rank test. RESULTS:
      Each cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals,
      with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years,
      respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian
      cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person
      years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic
      stroke risk imposed by ovarian cancer was more prominent in patients under 50
      years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33;
      P = 0.005). Significant risk factors predicting stroke development were age 50
      years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes
      mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P =
      0.017), especially platinum-based regimens. CONCLUSIONS: Ovarian cancer patients
      were at an increased risk of developing ischemic stroke. Age, hypertension,
      diabetes, and chemotherapy treatment were independent risk factors.

PMID- 24661586
TI  - Correction required.

PMID- 24661585
TI  - Effects and risks associated with novel psychoactive substances: mislabeling and
      sale as bath salts, spice, and research chemicals.
AB  - BACKGROUND: The number of newly reported psychoactive substances in Europe is now
      higher than ever. In order to evade legal restrictions, old and novel
      psychoactive substances from medical research and their derivatives are commonly
      mislabeled as "not for human consumption" and offered for sale on the Internet
      and elsewhere. Such substances are widely taken by young people as "club drugs."
      Their consumption must be considered in the differential diagnosis of
      psychiatric, neurological, cardiovascular, or metabolic disturbances of unclear
      origin in a young patient. METHOD: Selective review of pertinent literature
      retrieved by a PubMed search, including publications by government-sponsored
      organizations. RESULTS: From 2010 to 2012, 163 substances were reported to the
      European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), mostly either
      synthetic cannabinoids (39.3%) or synthetic cathinones (16.6%). Synthetic
      cannabinoids alter mood and perception; intoxications cause agitation, tachy
      cardia, and arterial hypertension. Synthetic cathinones are hallucinogenic
      stimulants with predominantly cardiovascular and psychiatric side effects. Severe
      intoxications cause serotonin syndrome and potentially fatal rhabdomyolysis.
      Substances in either of these classes often escape detection in screening tests.
      CONCLUSION: Young persons who present with agitation and cardiovascular and/or
      psychiatric manifestations of unclear origin and whose drug screening tests are
      negative may be suffering from an intoxication with a novel psychoactive
      substance. Physicians should know the classes of such substances and their
      effects. Targeted toxicological analysis can be carried out in a toxicology
      laboratory or a facility for forensic medicine.

PMID- 24661587
TI  - Restrictive diets are to be avoided.

PMID- 24661588
TI  - In reply.

PMID- 24661589
TI  - High vaccination rate is crucial.

PMID- 24661590
TI  - In reply.

PMID- 24661592
TI  - Abstracts of the 35th Annual Meeting of the American Brachytherapy Society, April
      3-5, 2014, San Diego, CA.

PMID- 24661591
TI  - Acute otitis media--a structured approach.
AB  - BACKGROUND: Two-thirds of all children have an episode of acute otitis media
      (AOM) before their third birthday. Antibiotic treatment is often given
      immediately, even though adequate scientific evidence for this practice is
      lacking. METHOD: This review is based on a selective literature search including
      previously published evidence-based recommendations, particularly those of the
      current American guidelines. RESULTS: A purulent tympanic effusion, possibly
      associated with inflammation of the tympanic membrane, is indicative of AOM. Only
      some patients with AOM need immediate antibiotic treatment: children with severe
      otalgia and/or fever of 39.0 degrees C or above, infants under 6 months of age,
      and children with certain specific risk factors, including immune deficiency and
      Down syndrome. In other cases, symptomatic treatment is appropriate. Antibiotic
      therapy (preferably with amoxicillin) should be initiated only if the symptoms
      and signs do not improve within two to three days. CONCLUSION: As the currently
      available data are not fully consistent, there is still a need for controlled
      trials with well-defined endpoints to determine the relative benefits of
      immediate antibiotic treatment versus two to three days of watchful waiting.

PMID- 24661593
TI  - Factors associated with the change in prevalence of cardiomyopathy at delivery in
      the period 2000-2009: a population-based prevalence study.
AB  - OBJECTIVE: Cardiomyopathy (CM) at delivery is increasing in prevalance. The
      objective of this study was to determine which medical conditions are
      attributable to this increasing prevalance. DESIGN: Population prevalence study
      from 2000 to 2009. SETTING: The Nationwide Inpatient Sample (NIS). SAMPLE:
      Pregnant women admitted for delivery were identified in the NIS for the years
      2000-2009. METHODS: Temporal trends in pre-existing medical conditions and in
      medical and obstetric complications at delivery admissions were determined by
      linear regression. The change in the prevalence of CM among all pregnant women
      was compared with the change in the prevalance of CM among pregnant women without
      pre-existing conditions or complications. MAIN OUTCOME MEASURE: Prevalence of CM.
      RESULTS: The prevalence of CM increased from 0.25 per 1000 deliveries in 2000 to
      0.43 per 1000 deliveries in 2009 (P < 0.0001). Women with chronic hypertension
      had increased odds of developing CM compared with women without chronic
      hypertension (odds ratio, OR, 13.2; 95% confidence interval, 95% CI, 12.5-13.7).
      The linear increase in chronic hypertension over the 10-year period was the
      single identified pre-existing medical condition that explained the increasing
      prevalence of CM at delivery (P = 0.005 for the differences in slopes for linear
      trends). CONCLUSIONS: Pregnant women with chronic hypertenion are at an increased
      risk for CM at delivery, and the increasing prevalence of chronic hypertension is
      an important factor associated with the increasing prevalence of CM at the time
      of delivery. Among women without chronic hypertension, the prevalence of CM at
      delivery did not change during the time period.

PMID- 24661594
TI  - Characterisation of systemic reactions to subcutaneous immunotherapy with
      airborne allergens and classification according to WAO 2010.
AB  - BACKGROUND: Systemic reactions (SR) to subcutaneous immunotherapy (SCIT) are rare
      but potentially severe. The use of different definitions and classifications
      hampered comparability between studies. AIMS: To determine the frequency of SR to
      SCIT with airborne allergens, and to characterise and classify them according to
      the WAO 2010 recommendations. METHODS: Cross-sectional, retrospective study. Data
      on patients, immunotherapy and SR to SCIT were collected from the SCIT record
      forms. During the study period, 22,332 SCIT injections were administered (3732
      patients). RESULTS: A total of 26 SR (0.1% of administrations) were recorded in
      16 (0.6%) patients (median age 22 years, nine males, all with rhinitis and nine
      with asthma). Twenty-one (81%) SR occurred during the induction phase; eight
      (31%) in the first hour after administration. According to the WAO 2010
      classification, 12 (46%) were grade 1 and 14 (54%) were grade 2. Most grade 2
      reactions occurred in asthmatics, presented as mild asthma symptoms and resolved
      without need for medical observation. Only two individuals without asthma
      presented grade 2 reactions, both with concurrent cutaneous and low respiratory
      symptoms; both required medical observation and treatment despite late onset; 82%
      (n=12) of grade 2 reactions were late. No grade 3-5 reactions were registered and
      only one patient needed adrenaline treatment. No risk factors for SR to SCIT were
      identified in this study. CONCLUSIONS: SCIT is a safe treatment when administered
      by trained staff. The WAO 2010 classification might be useful for retrospectively
      classifying the severity of reactions, although its usefulness in treatment
      decision needs further research.

PMID- 24661595
TI  - Nasal endoscopic findings and nasal symptoms in patients with asthma: a clinical
      study from a rhinological perspective.
AB  - OBJECTIVE: Allergic rhinitis (AR), non-allergic rhinitis (NAR), chronic
      rhinosinusitis with nasal polyps (CRSwNP), and chronic rhinosinusitis without
      nasal polyps (CRSsNP) occur frequently in asthmatic patients. We evaluated nasal
      symptoms and nasal endoscopic findings in patients with asthma and correlated
      them to asthma severity. METHODS: Subjects (n=150) with asthma completed
      questionnaires designed to provide information related to asthma and nasal
      disease. Patients were divided into four groups based on asthma severity.
      Pulmonary function tests, skin-prick tests (SPTs) and nasal endoscopy were
      performed on every patient. Clinical findings were compared in asthma patients by
      rhinologists. RESULTS: The total incidence of AR, NAR, CRSwNP and CRSsNP in these
      patients with asthma was 76%. By using Fisher's Exact Test, there was no
      statistical significance between asthma severity and the incidence of AR, NAR,
      CRSwNP and CRSsNP (P=0.311). There was a significant difference in the total
      nasal symptoms score among subjects with different grades of asthma (P=0.002).
      However, there were no significant differences in the total Lund-Kennedy
      endoscopic score (LKS) (P=0.736). The nasal endoscopic scores were significantly
      correlated at a high degree with the nasal symptoms score (P=0.000). A
      significant correlation was found between the nasal endoscopic score and the
      duration of asthma in the patients with different grades of asthma (P<0.05).
      CONCLUSIONS: The relationship between rhinitis and asthma is complex. Nasal
      airways should become part of standard clinical assessment and follow-up in
      patients with asthma.

PMID- 24661596
TI  - Medical students call for national standards in anatomical education.
AB  - The diminishing number of hours dedicated to formal instruction in anatomy has
      led to a debate within medical education as to the level required for safe
      clinical practice. We provide a review of the current state of anatomical
      education in Australian medical schools and state the case for national
      standards. In light of the review presented, council members of the Australian
      Medical Students' Association voted to affirm that consideration should be given
      to developing undergraduate learning goals for anatomy, providing a codified
      medical student position on the teaching of anatomy in Australian medical
      schools. Crucially, the position states that time-intensive methods of
      instruction such as dissection should be a rite of passage for medical students
      in the absence of evidence demonstrating the superiority of modern teaching
      methods. We believe the bodies with a vested interest in the quality of medical
      graduates, namely the Australian Medical Council, Medical Deans Australia & New
      Zealand, and the postgraduate colleges should collaborate and develop clear
      guidelines that make explicit the core knowledge of anatomy expected of medical
      graduates at each stage of their career with a view to safe clinical practice. In
      addition, Australian universities have a role to play in conducting further
      research into contemporary learning styles and the most efficacious methods of
      delivering anatomical education.

PMID- 24661597
TI  - NF-kappaB activation and severity of gastritis in Helicobacter pylori-infected
      children and adults.
AB  - BACKGROUND: In contrast to adults, Helicobacter pylori gastritis in children is
      reported as milder and ulcer disease as uncommon, but unequivocal data are
      lacking. OBJECTIVES: To compare the frequency of gastro-duodenal ulcers in
      children and adults as well as the proportion of Helicobacter pylori infection in
      these patients and to study the effect of chronological age on NF-kappaB
      activation and on severity of gastritis. DESIGN: Patients referred in one
      pediatric and one adult facility for upper GI endoscopy were included. Gastric
      biopsies were obtained in consecutive Helicobacter pylori-infected patients and
      age-matched negative controls for immunohistochemistry and electrophoresis
      mobility shift assay. Three age groups were defined: younger than 8 years, 8-17
      years, and adults. RESULTS: Peptic ulcer disease was less frequent in children
      and less frequently associated with Helicobacter pylori infection. When comparing
      infected subjects to controls, densities of neutrophils and CD20 cells in the
      lamina propria increased in all age groups, CD3 cells increasing only in patients
      older than 8 years and CD8 cells only in adults. NF-kappaB-p65-positive cells
      were also increased only in infected adults as well as NF-kappaB-binding
      activity. A positive correlation was found between age and densities of
      neutrophils and CD3, but not of CD8 or CD20 cells. CONCLUSION: Peptic ulcer
      disease was less frequent in children and less frequently caused by Helicobacter
      pylori infection. The different clinical outcome of the infection in children can
      be the consequence of the lower mucosal immune response.

PMID- 24661598
TI  - Morphopathological aspects of healthy nails and nails affected by onychomycosis.
AB  - Patients of onychomycosis are common in the dermatology practice. Contemporary
      morphology creates opportunities to study the functional units of the nail when
      such infections occur from morphopathological point of view. There were 22 nails
      biopsies from onychomycosis patients taken for the research of morphopathological
      changes in the thickened nail plate affected by onychomycosis. Samples of
      cadaverous' nails were used as a control material. The material was stained with
      haematoxylin and eosin and immunohistochemical methods. Terminal deoxynucleotidyl
      transferase dUTP nick end labelling reaction and periodic acid-Schiff reaction
      were also performed. We found patchy hypertrophy in the granulose layer of the
      epidermis, with focal acanthosis. In the horn layer, we identified nests of
      parakeratosis of various sizes, with incorporations of homogenous and eosinophil
      masses. We found high levels of interleukin 6 and interleukin 10 positive cells
      in the nail bed and in the bloodstream. Interleukin 1, however, was not a part of
      any of the functional units of any of the nails. Significant amount of fibres
      containing human beta defensin-2 were found in the bed and plate of the nail.
      Therefore one can conclude that as regards the nails affected by onychomycosis,
      the most effective morphopathogenical processes include cytokine and defensin
      excretion occurrence in the nail bed.

PMID- 24661599
TI  - Calmodulin modulates insect odorant receptor function.
AB  - Insect odorant receptors (ORs) are heteromeric complexes of an odor-specific
      receptor protein (OrX) and a ubiquitous co-receptor protein (Orco). The ORs
      operate as non-selective cation channels, also conducting Ca(2+) ions. The Orco
      protein contains a conserved putative calmodulin (CaM)-binding motif indicating a
      role of CaM in its function. Using Ca(2+) imaging to monitor OR activity we
      investigated the effect of CaM inhibition on the function of OR proteins. Ca(2+)
      responses elicited in Drosophila olfactory sensory neurons by stimulation with
      the synthetic OR agonist VUAA1 were reduced and prolonged by CaM inhibition with
      the potent antagonist W7 but not with the weak antagonist W5. A similar effect
      was observed for Orco proteins heterologously expressed in CHO cells when CaM was
      inhibited with W7, trifluoperazine or chlorpromazine, or upon overexpression of
      CaM-EF-hand mutants. With the Orco CaM mutant bearing a point mutation in the
      putative CaM site (K339N) the Ca(2+) responses were akin to those obtained for
      wild type Orco in the presence of W7. There was no uniform effect of W7 on Ca(2+)
      responses in CHO cells expressing complete ORs (Or22a/Orco, Or47a/Orco,
      Or33a/Orco, Or56a/Orco). For Or33a and Or47a we observed no significant effect of
      W7, while it caused a reduced response in cells expressing Or22a and a shortened
      response for Or56a. 

PMID- 24661600
TI  - Crystal growth and characterization of an organic nonlinear optical single
      crystal: 2,3-Dimethyl-N-[4-(Nitro) benzylidene] aniline.
AB  - An organic nonlinear optical material 2,3-Dimethyl-N-[4-(Nitro) benzylidene]
      aniline was synthesized by condensation reaction. The single crystals were grown
      by the slow evaporation technique at room temperature using ethyl acetate as
      solvent with large in size and having transparent nature. The unit cell
      parameters were determined and belong to a noncentrosymmetric orthorhombic
      crystal structure by single crystal X-ray diffraction. The crystalline nature of
      the synthesized material was recorded by the powder X-ray diffraction pattern.
      The molecular structure of the grown material was investigated by proton and
      carbon nuclear magnetic resonance, mass spectrum analysis. Functional groups were
      identified by the vibration spectrum analysis. The optical absorbance of the
      grown crystal was ascertained by Ultraviolet-Visible spectrum. Thermal behaviour
      and stability of the grown material was investigated by thermo
      gravimetric/differential thermal analysis. The nonlinear optic conversion
      efficiency was determined by powder technique and found to be 4.08 times greater
      that of KDP as a standard reference. 

PMID- 24661601
TI  - Inter-hydrogen bond coupling in crystals with molecular chains in their lattices
      investigated by polarized IR spectroscopy: 4-Bromo-3,5-dimethylpyrazole and 3,4
      dimethoxyphenylacetic acid.
AB  - We report the results of the experimental and theoretical studies of the
      polarized IR crystalline spectra of 4-bromo-3,5-dimethylpyrazole (4Br35DMPz) and
      3,4-dimethoxyphenylacetic acid (34DMPAA) as well as the spectra of their
      deuterium-bonded analogues. The results of model calculations of the temperature
      impact exerted on to the band shapes measured in the X-H- and X-D bond stretching
      vibration regions, performed on the basis of the "strong-coupling" model, are
      also shown. These studies confirm a direct relationship between the spectral
      properties in IR and the electronic structure of the associating molecules in the
      crystals. Two different competing exciton coupling mechanisms involving hydrogen
      bonds, the "tail-to-head" (TH) in 4Br35DMPz and the "side-to-side" coupling in
      34DMPAA, were recognized. The molecular electronic structure determines the
      relative contribution of each individual vibrational exciton coupling mechanism
      in the spectra generation. It also strongly influences the temperature-induced
      evolution of the Davydov-splitting effects in the crystalline spectra. Dynamical
      co-operative interactions responsible for a non-random distribution of protons
      and deuterons in the crystal hydrogen bonds can also be identified in the
      investigated systems. 

PMID- 24661602
TI  - Evidence based practice beliefs and implementation among nurses: a cross
      sectional study.
AB  - BACKGROUND: Having a positive attitude towards evidence-based practice and being
      able to see the value of evidence-based practice for patients have been reported
      as important for the implementation of evidence-based practice among nurses.The
      aim of this study was to map self-reported beliefs towards EBP and EBP
      implementation among nurses, and to investigate whether there was a positive
      correlation between EBP beliefs and EBP implementation. METHOD: We carried out a
      cross-sectional study among 356 nurses at a specialist hospital for the treatment
      of cancer in Norway. The Norwegian translations of the Evidence-based Practice
      Belief Scale and the Evidence-based Practice Implementation Scale were used.
      RESULTS: In total, 185 nurses participated in the study (response rate 52%). The
      results showed that nurses were positive towards evidence-based practice, but
      only practised it to a small extent. There was a positive correlation (r) between
      beliefs towards evidence-based practice and implementation of evidence-based
      practice (r = 0.59, p = 0.001).There was a statistical significant positive, but
      moderate correlation between all the four subscales of the EBP Beliefs Scale
      (beliefs related to: 1) knowledge, 2) resources, 3) the value of EBP and 4)
      difficulty and time) and the EBP Implementation Scale, with the highest
      correlation observed for beliefs related to knowledge (r = 0.38, p < .0001).
      Participants who had learned about evidence-based practice had significantly
      higher scores on the Evidence-based Practice Belief Scale than participants who
      were unfamiliar with evidence-based practice. Those involved in evidence-based
      practice working groups also reported significantly higher scores on the Evidence
      based Practice Belief Scale than participants not involved in these groups.
      CONCLUSION: This study shows that nurses have a positive attitude towards
      evidence-based practice, but practise it to a lesser extent. There was a positive
      correlation between beliefs about evidence-based practice and implementation of
      evidence-based practice. Beliefs related to knowledge appear to have the greatest
      effect on implementation of evidence-based practice. Having knowledge and taking
      part in evidence-based practice working groups seem important.

PMID- 24661603
TI  - Bilateral blindness following Russell's viper bite - a rare clinical
      presentation: a case report.
AB  - INTRODUCTION: Russell's viper (Daboia russelii) is one of the most common
      medically important snakes reported in Sri Lanka. Its envenomation leads to
      significant mortality and morbidity with local, hematological, neurological and
      renal complications. Here we report the case of a patient who presented with
      bilateral blindness secondary to a bilateral posterior circulation ischemic
      stroke instead of the usual neurological manifestations of Russell's viper
      envenomation. There were no reported cases of cortical blindness following a
      Russell's viper bite. Only a few reported cases of ischemic strokes following a
      Russell's viper bite were found in the literature. CASE PRESENTATION: A 54-year
      old Sri Lankan woman developed bilateral blindness due to a posterior circulation
      infarct following Russell's viper envenomation. CONCLUSION: Ischemic stroke
      following a Russell's viper bite is very rare and cortical blindness is not
      reported as the clinical presentation. Also, we emphasize the importance of
      considering the possibility of ischemic stroke in patients who develop unusual
      neurological manifestations following Russell's viper envenomation.

PMID- 24661604
TI  - The peptide semax affects the expression of genes related to the immune and
      vascular systems in rat brain focal ischemia: genome-wide transcriptional
      analysis.
AB  - BACKGROUND: The nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly
      Pro) has proved efficient in the therapy of brain stroke; however, the molecular
      mechanisms underlying its action remain obscure. Our genome-wide study was
      designed to investigate the response of the transcriptome of ischemized rat brain
      cortex tissues to the action of Semax in vivo. RESULTS: The gene-expression
      alteration caused by the action of the peptide Semax was compared with the gene
      expression of the "ischemia" group animals at 3 and 24 h after permanent middle
      cerebral artery occlusion (pMCAO). The peptide predominantly enhanced the
      expression of genes related to the immune system. Three hours after pMCAO, Semax
      influenced the expression of some genes that affect the activity of immune cells,
      and, 24 h after pMCAO, the action of Semax on the immune response increased
      considerably. The genes implicated in this response represented over 50% of the
      total number of genes that exhibited Semax-induced altered expression. Among the
      immune-response genes, the expression of which was modulated by Semax, genes that
      encode immunoglobulins and chemokines formed the most notable groups. In response
      to Semax administration, 24 genes related to the vascular system exhibited
      altered expression 3 h after pMCAO, whereas 12 genes were changed 24 h after
      pMCAO. These genes are associated with such processes as the development and
      migration of endothelial tissue, the migration of smooth muscle cells,
      hematopoiesis, and vasculogenesis. CONCLUSIONS: Semax affects several biological
      processes involved in the function of various systems. The immune response is the
      process most markedly affected by the drug. Semax altered the expression of genes
      that modulate the amount and mobility of immune cells and enhanced the expression
      of genes that encode chemokines and immunoglobulins. In conditions of rat brain
      focal ischemia, Semax influenced the expression of genes that promote the
      formation and functioning of the vascular system.The immunomodulating effect of
      the peptide discovered in our research and its impact on the vascular system
      during ischemia are likely to be the key mechanisms underlying the
      neuroprotective effects of the peptide.

PMID- 24661605
TI  - The challenge of intratumour heterogeneity in precision medicine.
AB  - Cells within tumours have diverse genomes and epigenomes and interact
      differentially with their surrounding microenvironment generating intratumour
      heterogeneity, which has critical implications for treating cancer patients.
      Understanding the cellular and microenvironment composition and characteristics
      in individual tumours is critical to stratify the patient population that is
      likely to benefit from specific treatment regimens. Here, we will review the
      current understanding of intratumour heterogeneity at the genomic, epigenomic and
      microenvironmental levels. We will also discuss the clinical implications and the
      challenges posed by intratumour heterogeneity and evaluate noninvasive methods
      such as circulating biomarkers to characterize the cellular diversity of tumours.
      Comprehensive assessment of the molecular features of patients based on tumour
      specimen characterization (including intratumour spatial and temporal
      variations), ancillary noninvasive methods (such as circulating biomarkers and
      molecular imaging approaches) and the correct design of clinical trials are
      required to guide administration of targeted therapy and to control therapeutic
      resistance. Finding the means to accurately determine and effectively control
      tumour heterogeneity and translate these achievements into patient benefit are
      major goals in modern oncology. 

PMID- 24661606
TI  - Automatic quality assessment and peak identification of auditory brainstem
      responses with fitted parametric peaks.
AB  - The recording of the auditory brainstem response (ABR) is used worldwide for
      hearing screening purposes. In this process, a precise estimation of the most
      relevant components is essential for an accurate interpretation of these signals.
      This evaluation is usually carried out subjectively by an audiologist. However,
      the use of automatic methods for this purpose is being encouraged nowadays in
      order to reduce human evaluation biases and ensure uniformity among test
      conditions, patients, and screening personnel. This article describes a new
      method that performs automatic quality assessment and identification of the
      peaks, the fitted parametric peaks (FPP). This method is based on the use of
      synthesized peaks that are adjusted to the ABR response. The FPP is validated, on
      one hand, by an analysis of amplitudes and latencies measured manually by an
      audiologist and automatically by the FPP method in ABR signals recorded at
      different stimulation rates; and on the other hand, contrasting the performance
      of the FPP method with the automatic evaluation techniques based on the
      correlation coefficient, FSP, and cross correlation with a predefined template
      waveform by comparing the automatic evaluations of the quality of these methods
      with subjective evaluations provided by five experienced evaluators on a set of
      ABR signals of different quality. The results of this study suggest (a) that the
      FPP method can be used to provide an accurate parameterization of the peaks in
      terms of amplitude, latency, and width, and (b) that the FPP remains as the
      method that best approaches the averaged subjective quality evaluation, as well
      as provides the best results in terms of sensitivity and specificity in ABR
      signals validation. The significance of these findings and the clinical value of
      the FPP method are highlighted on this paper. 

PMID- 24661607
TI  - Spatial fuzzy c-means algorithm with adaptive fuzzy exponent selection for robust
      vermilion border detection in healthy and diseased lower lips.
AB  - INTRODUCTION: Accurate lip contour identification is demanding since variations
      in color, form and surface texture, even in normal lips, introduce artifacts in
      non-adapted segmentation algorithms. Herein, a method for vermilion border
      detection and quantification in healthy and diseased lower lips is presented.
      AIM: To quantify the morphological irregularities of lower lip border, to
      validate its discriminative power in solar cheilosis diagnosis and to provide
      supportive tools toward, cost effective, non invasive, disease monitoring.
      MATERIALS: Segmentation algorithm for lower lip border was based on spatial fuzzy
      c-means clustering algorithm with adaptive selection of fuzzy exponent m. Lip
      features measuring morphological lip border deviations were estimated. The method
      of lip border extraction and quantitative description was evaluated in a gold
      standard set of 25 young volunteers without onset of lip diseases. Quantitative
      descriptors were evaluated in terms of correct classification rates in
      differentiating 30 healthy control cases from 41 patients with solar cheilosis
      and were further applied to quantify the therapeutic outcome after
      immunocryosurgery in eight patients with solar cheilosis. RESULTS: Adaptive
      estimation of fuzzy exponent m substantially boosted the segmentation quality in
      gold standard cases yielding quite smooth lip contours and uniformly low values
      of lip irregularity features. Discriminant analysis highlighted the distance
      between the extracted and modeled vermilion border as a feature with excellent
      diagnostic accuracy (sensitivity and specificity 98% and 93% respectively).
      Results on patients with solar cheilosis followed up after treatment with
      immunocryosurgery showed that proposed quantitative lip marker was able to trace
      the improvement of disease after treatment. CONCLUSION: Correct lip border
      recognition is the prerequisite for extracting essential morphological
      descriptors from lips with epithelial diseases like solar cheilosis. In this
      paper we presented an efficient method for the automatic identification and
      quantitative description of lower lip vermilion border morphology in health and
      disease using digital photography and image analysis techniques.

PMID- 24661608
TI  - Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham
      Heart Study Offspring Cohort.
AB  - The intake of carbohydrates has been evaluated cross-sectionally, but not
      longitudinally in an ageing American adult population. The aim of the present
      study was to examine trends in the intake of dietary carbohydrates and their
      major food sources among the Framingham Heart Study Offspring (FOS) cohort, which
      had been uniquely tracked for 17 years in the study. The FOS cohort was recruited
      in 1971-1975. Follow-up examinations were conducted, on average, every 4 years.
      Dietary data collection began in 1991 (examination 5) using a validated semi
      quantitative FFQ. The study included 2894 adults aged >= 25 years with complete
      dietary data in at least three examinations from 1991 to 2008. Descriptive
      statistics were generated using SAS version 9.3, and a repeated-measures model
      was used to examine trends in the intake of carbohydrates and their food sources
      in the whole sample, and by sex and BMI category. Over 17 years of follow-up, the
      percentage of energy from total carbohydrates (51.0-46.8 %; P for trend < 0.001)
      and total sugars (18.2-16.6 %; P for trend < 0.001) decreased. There was a
      decrease in the percentage of energy from fructose (5.4-4.7 %; P for trend <
      0.001) and sucrose (9.8-8.8 %; P for trend < 0.001). Dietary fibre intake
      increased (18.0-19.2 g/d; P for trend < 0.001). The number of weekly servings of
      yeast bread, soft drinks/soda, cakes/cookies/quick breads/doughnuts, potatoes,
      milk, pasta, rice and cooked grains, fruit juice/drinks, potato chips/maize
      chips/popcorn, and lunch foods (e.g. pizzas and burgers) decreased significantly
      (P for trend < 0.001), while the intake of ready-to-eat cereals, legumes, fruits,
      dairy products, candy and ice cream/sherbet/frozen yogurt increased significantly
      (P for trend<0.04). Similar trends were observed when the analyses were
      stratified by sex and BMI. The present results suggest favourable trends in
      dietary carbohydrate consumption, but dietary guidelines for fruits, vegetables
      and fibre were not met in this cohort.

PMID- 24661610
TI  - Abstracts of the 16th Asia Pacific League of Associations for Rheumatology
      Congress, 31 March-4 April 2014, Cebu City, Philippines.

PMID- 24661609
TI  - Unsupervised tissue segmentation from dynamic contrast-enhanced magnetic
      resonance imaging.
AB  - OBJECTIVE: Design, implement, and validate an unsupervised method for tissue
      segmentation from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
      METHODS: For each DCE-MRI acquisition, after a spatial registration phase, the
      time-varying intensity of each voxel is represented as a sparse linear
      combination of adaptive basis signals. Both the basis signals and the sparse
      coefficients are learned by minimizing a functional consisting of a data fidelity
      term and a sparsity inducing penalty. Tissue segmentation is then obtained by
      applying a standard clustering algorithm to the computed representation. RESULTS:
      Quantitative estimates on two real data sets are presented. In the first case,
      the overlap with expert annotation measured with the DICE metric is nearly 90%
      and thus 5% more accurate than state-of-the-art techniques. In the second case,
      assessment of the correlation between quantitative scores, obtained by the
      proposed method against imagery manually annotated by two experts, achieved a
      Pearson coefficient of 0.83 and 0.87, and a Spearman coefficient of 0.83 and
      0.71, respectively. CONCLUSIONS: The sparse representation of DCE MRI signals
      obtained by means of adaptive dictionary learning techniques appears to be well
      suited for unsupervised tissue segmentation and applicable to different clinical
      contexts with little effort.

PMID- 24661611
TI  - Phytochemical and biological studies of Stachys species in relation to
      chemotaxonomy: a review.
AB  - The genus Stachys is comprised of about 300 species spread throughout the world,
      hence representing one of the largest genera of the Lamiaceae. Several Stachys
      species have been exploited in traditional medicine as astringent, wound-healing,
      anti-diarrhoeal, anti-nephritic and anti-inflammatory agents. Moreover,
      antimicrobial, antioxidant and cytotoxic activities of some Stachys species are
      documented. Iridoids, flavonoids, phenolic acids and diterpenoids are reported as
      secondary metabolites of different species of this genus. The aim of the present
      review is to summarize and to highlight the recent advances in current knowledge
      on Stachys species and to compile reports of chemical constituents isolated from
      the genus Stachys over the past decades, together with their structural features,
      biological activities, and structure-activity relationships. Diversity of
      chemical constituents is discussed in relationship with current Stachys
      infrageneric taxonomy, classification and relationships with systematically close
      genera. 

PMID- 24661612
TI  - Diferulic acids in the cell wall may contribute to the suppression of shoot
      growth in the first phase of salt stress in maize.
AB  - In the first phase of salt stress the elongation growth of maize shoots is
      severely affected. The fixation of shape at the end of the elongation phase in
      Poaceae leaves has frequently been attributed to the formation of phenolic cross
      links in the cell wall. In the present work it was investigated whether this
      process is accelerated under salt stress in different maize hybrids. Plants were
      grown in nutrient solution in a growth chamber. Reduction of shoot fresh mass was
      50% for two hybrids which have recently been developed for improved salt
      resistance (SR 03, SR 12) and 60% for their parental genotype (Pioneer 3906). For
      SR 12 and Pioneer 3906, the upper three leaves were divided into elongated and
      elongating tissue and cell walls were isolated from which phenolic substances and
      neutral sugars were determined. Furthermore, for the newly developed hybrids the
      activity of phenolic peroxidase in the cell wall was analysed in apoplastic
      washing fluids and after sequential extraction of cell-wall material with CaCl2
      and LiCl. The concentration of ferulic acid, the predominant phenolic cross
      linker in the grass cell wall, was about 5mgg(-1) dry cell wall in elongating and
      in elongated tissue. The concentration of diferulic acids (DFA) was 2-3mgg(-1)
      dry cell wall in both tissues. Salt stress increased the concentration of ferulic
      acid (FA) and DFA in the parental genotype Pioneer 3906, but not in SR 12. Both
      genotypes showed an increase in arabinose, which is the molecule at which FA and
      DFA are coupled to interlocking arabinoxylan polymers. In SR 12, the activity of
      phenolic peroxidase was not influenced by salt stress. However, in SR 03 salt
      stress clearly increased the phenolic peroxidase activity. Results are consistent
      with the hypothesis that accelerated oxidative fixation of shape contributes to
      growth suppression in the first phase of salt stress in a genotype-specific
      manner. 

PMID- 24661613
TI  - Clinical decision making and cardiovascular risk factors: what about the Heart
      Team?

PMID- 24661614
TI  - The New South Wales Allied Health Workplace Learning Study: barriers and enablers
      to learning in the workplace.
AB  - BACKGROUND: Workplace learning refers to continuing professional development that
      is stimulated by and occurs through participation in workplace activities.
      Workplace learning is essential for staff development and high quality clinical
      care. The purpose of this study was to explore the barriers to and enablers of
      workplace learning for allied health professionals within NSW Health. METHODS: A
      qualitative study was conducted with a purposively selected maximum variation
      sample (n =46) including 19 managers, 19 clinicians and eight educators from 10
      allied health professions. Seven semi-structured interviews and nine focus groups
      were audio-recorded and transcribed. The 'framework approach' was used to guide
      the interviews and analysis. Textual data were coded and charted using an
      evolving thematic framework. RESULTS: Key enablers of workplace learning included
      having access to peers, expertise and 'learning networks', protected learning
      time, supportive management and positive staff attitudes. The absence of these
      key enablers including heavy workload and insufficient staffing were important
      barriers to workplace learning. CONCLUSION: Attention to these barriers and
      enablers may help organisations to more effectively optimise allied health
      workplace learning. Ultimately better workplace learning may lead to improved
      patient, staff and organisational outcomes.

PMID- 24661615
TI  - Vitamin D3 potentiates the antitumorigenic effects of arsenic trioxide in human
      leukemia (HL-60) cells.
AB  - BACKGROUND: Arsenic trioxide (ATO) is a novel form of therapy that has been found
      to aid acute promyelocytic leukemia (APL) patients. Our laboratory has
      demonstrated that ATO-induced cytotoxicity in human leukemia (HL-60) cells is
      mediated by oxidative stress. Pro-oxidants have been known to play a role in free
      radical-mediated oxidative stress. Vitamin D3, (Vit D3) an active metabolite of
      vitamin D has been reported to inhibit the growth of number neoplasms such as
      prostate, breast, colorectal, leukemia, and skin cancers. The goal of the present
      research was to use (HL-60) cells as an in vitro test model to evaluate whether
      low doses of Vit D3 potentiate the toxicity of ATO and whether this toxic action
      is mediated via apoptotic mechanisms. METHOD: HL-60 cells were treated either
      with a pharmacologic dose of ATO alone and with several low doses of Vit D3. Cell
      survival was determined by MTT assay. Cell apoptosis was measured both by flow
      cytometry assessment, and DNA laddering assay. RESULTS: MTT assay indicated that
      Vit D3 co-treatment potentiates ATO toxicity in HL-60 cells in a dose dependent
      manner. A statistically significant and dose-dependent increase (p <0.05) was
      recorded in annexin V positive cells (apoptotic cells) with increasing doses of
      Vit D3 in ATO-treated cells. This finding was confirmed by the result of DNA
      laddering assay showing clear evidence of nucleosomal DNA fragmentation in
      vitamin and ATO co-treated cells. CONCLUSION: The present study indicates that
      Vit D3 potentiates the antitumor effects of ATO. This potentiation is mediated at
      least in part, through induction of phosphatidylserine externalization and
      nucleosomal DNA fragmentation. These findings highlight the potential impact of
      Vit D3 in promoting the pharmacological effect of ATO, suggesting a possible
      future role of Vit D3/ATO combination therapy in patients with acute
      promyelocytic leukemia (APL).

PMID- 24661616
TI  - Evaluation of T1rho as a potential MR biomarker for liver cirrhosis: comparison
      of healthy control subjects and patients with liver cirrhosis.
AB  - OBJECTIVES: The purpose of this study was to compare mean liver T1rho values in
      patients with liver cirrhosis and healthy control subjects in order to evaluate
      T1rho as a potential MR biomarker for liver cirrhosis. MATERIALS AND METHODS: Ten
      healthy control subjects (mean age 42.7 years; 6 female, 4 male) and 21 patients
      with clinically diagnosed liver cirrhosis (mean age 56.5 years; 5 female, 16
      male) were examined at 1.5 T (Magnetom Avanto, Siemens). T1rho-weighted images
      were acquired using a 2D TurboFLASH sequence (TR/TE 3/1.31 ms, FA 8 degrees , FoV
      309 * 380 mm, resolution 2 * 2 * 6 mm, acquisition time 15s, slice thickness 6mm)
      with spin-lock preparation. T1rho maps were calculated from five breath-hold
      measurements, performed with different spin-lock times (4, 8, 16, 32 and 48 ms).
      Mean liver T1rho values of healthy control subjects and patients with liver
      cirrhosis were calculated and compared using Student t-test. In addition, a
      receiver operating characteristic (ROC) curve analysis was performed to evaluate
      the utility of mean liver T1rho values for the prediction of liver cirrhosis.
      RESULTS: Mean liver T1rho values in patients with liver cirrhosis (57.4 +/- 7.4
      ms) were significantly higher than those of healthy subjects (47.8 +/- 4.2 ms;
      p=0.0007). According to the ROC analysis at a threshold value of 50.1 ms the
      sensitivity and specificity of mean liver T1rho in predicting liver cirrhosis
      were 90.5% and 90%, respectively. The area under the ROC curve was 0.90.
      CONCLUSION: Mean liver T1rho values in patients with liver cirrhosis were
      significantly higher than those in healthy subjects suggesting a potential role
      of liver T1rho as a MR biomarker for liver cirrhosis.

PMID- 24661617
TI  - Spontaneous oesophageal perforation after laparoscopic hiatus hernia repair.

PMID- 24661618
TI  - Inpatient child mortality by travel time to hospital in a rural area of Tanzania.
AB  - OBJECTIVE: To investigate the association, if any, between child mortality and
      distance to the nearest hospital. METHODS: The study was based on data from a 1
      year study of the cause of illness in febrile paediatric admissions to a district
      hospital in north-east Tanzania. All villages in the catchment population were
      geolocated, and travel times were estimated from availability of local transport.
      Using bands of travel time to hospital, we compared admission rates, inpatient
      case fatality rates and child mortality rates in the catchment population using
      inpatient deaths as the numerator. RESULTS: Three thousand hundred and eleven
      children under the age of 5 years were included of whom 4.6% died; 2307 were
      admitted from <3 h away of whom 3.4% died and 804 were admitted from >= 3 h away
      of whom 8.0% died. The admission rate declined from 125/1000 catchment population
      at <3 h away to 25/1000 at >= 3 h away, and the corresponding hospital
      deaths/catchment population were 4.3/1000 and 2.0/1000, respectively. Children
      admitted from more than 3 h away were more likely to be male, had a longer pre
      admission duration of illness and a shorter time between admission and death.
      Assuming uniform mortality in the catchment population, the predicted number of
      deaths not benefiting from hospital admission prior to death increased by 21.4%
      per hour of travel time to hospital. If the same admission and death rates that
      were found at <3 h from the hospital applied to the whole catchment population
      and if hospital care conferred a 30% survival benefit compared to home care, then
      10.3% of childhood deaths due to febrile illness in the catchment population
      would have been averted. CONCLUSIONS: The mortality impact of poor access to
      hospital care in areas of high paediatric mortality is likely to be substantial
      although uncertainty over the mortality benefit of inpatient care is the largest
      constraint in making an accurate estimate.

PMID- 24661619
TI  - Perioperative aspirin improves neurological outcome after focal brain ischemia
      possibly via inhibition of Notch 1 in rat.
AB  - BACKGROUND: Perioperative discontinuation of aspirin is often considered due to
      bleeding concern. We determined whether this discontinuation affected
      neurological outcome after brain ischemia. METHODS: Adult male Sprague-Dawley
      rats were subjected to a 90-minute right middle cerebral arterial occlusion
      (MCAO). They received 30 mg/kg/day aspirin via gastric gavage: 1) for 2 days at 5
      days before MCAO; 2) for 2 days at 5 days before MCAO and for 3 days after MCAO;
      3) for 7 days before MCAO; or 4) for 7 days before MCAO and for 3 days after
      MCAO. Neurological outcome was evaluated 3 days after the MCAO. Ischemic
      penumbral cortex was harvested 1 or 3 days after MCAO for determining Notch
      intracellular domain (NICD), IL-6 and IL-1beta levels. RESULTS: Aspirin given by
      regimen 2 and 3 but not by regimen 1 improved neurological outcome.
      Neuroprotection was achieved by N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S
      phenylglycine t-butyl ester (DAPT), a Notch activation inhibitor. DAPT and
      aspirin given only by regimen 2 and 3 reduced NICD, IL-6 and IL-1beta in the
      ischemic penumbral cortex. NICD was found in microglial nuclei. Microglial
      activation in the ischemic tissues was inhibited by aspirin. CONCLUSION: Aspirin
      use during the perioperative period provides neuroprotection. Inhibition of Notch
      activation and neuroinflammation may contribute to the neuroprotection of
      aspirin.

PMID- 24661620
TI  - Intrahepatic cholestasis of pregnancy is not associated with stillbirth in an
      Australian maternity population.

PMID- 24661621
TI  - Veterinary students' perceptions of their learning environment as measured by the
      Dundee Ready Education Environment Measure.
AB  - BACKGROUND: The Dundee Ready Education Environment Measure (DREEM) has been
      widely used to evaluate the learning environment within health sciences
      education, however, this tool has not been applied in veterinary medical
      education. The aim of this study was to evaluate the reliability and validity of
      the DREEM tool in a veterinary medical program and to determine veterinary
      students' perceptions of their learning environment. METHODS: The DREEM is a
      survey tool which quantitatively measures students' perceptions of their learning
      environment. The survey consists of 50 items, each scored 0-4 on a Likert Scale.
      The 50 items are subsequently analysed within five subscales related to students'
      perceptions of learning, faculty (teachers), academic atmosphere, and self
      perceptions (academic and social). An overall score is obtained by summing the
      mean score for each subscale, with an overall possible score of 200. All students
      in the program were asked to complete the DREEM. Means and standard deviations
      were calculated for the 50 items, the five subscale scores and the overall score.
      Cronbach's alpha was determined for the five subscales and overall score to
      evaluate reliability. Confirmatory factor analysis was used to evaluate construct
      validity. RESULTS: 224 responses (53%) were received. The Cronbach's alpha for
      the overall score was 0.93 and for the five subscales were; perceptions of
      learning 0.85, perceptions of faculty 0.79, perceptions of atmosphere 0.81,
      academic self-perceptions 0.68, and social self-perceptions 0.72. Construct
      validity was determined to be acceptable (p < 0.001) and all items contributed to
      the overall validity of the DREEM. The overall DREEM score was 128.9/200, which
      is a positive result based on the developers' descriptors and comparable to other
      health science education programs. Four individual items of concern were
      identified by students. CONCLUSIONS: In this setting the DREEM was a reliable and
      valid tool to measure veterinary students' perceptions of their learning
      environment. The four items identified as concerning originated from four of the
      five subscales, but all related to workload. Negative perceptions regarding
      workload is a common concern of students in health education programs. If not
      addressed, this perception may have an unfavourable impact on veterinary
      students' learning environment.

PMID- 24661622
TI  - Maternal caloric restriction partially rescues the deleterious effects of
      advanced maternal age on offspring.
AB  - While many studies have focused on the detrimental effects of advanced maternal
      age and harmful prenatal environments on progeny, little is known about the role
      of beneficial non-Mendelian maternal inheritance on aging. Here, we report the
      effects of maternal age and maternal caloric restriction (CR) on the life span
      and health span of offspring for a clonal culture of the monogonont rotifer
      Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent
      fasting (IF) had increased life span compared with mothers fed ad libitum (AL).
      With increasing maternal age, life span and fecundity of female offspring of AL
      fed mothers decreased significantly and life span of male offspring was
      unchanged, whereas body size of both male and female offspring increased.
      Maternal CR partially rescued these effects, increasing the mean life span of AL
      fed female offspring but not male offspring and increasing the fecundity of AL
      fed female offspring compared with offspring of mothers of the same age. Both
      maternal CR regimens decreased male offspring body size, but only maternal IF
      decreased body size of female offspring, whereas maternal CCR caused a slight
      increase. Understanding the genetic and biochemical basis of these different
      maternal effects on aging may guide effective interventions to improve health
      span and life span. 

PMID- 24661623
TI  - Sequential processing in the equiprobable auditory Go/NoGo task: children vs.
      adults.
AB  - OBJECTIVE: To compare sequential processing in the unwarned auditory equiprobable
      Go/NoGo task in children and adults, in the context of a recently developed adult
      schema. METHODS: Adult and child samples completed an equiprobable auditory
      Go/NoGo task while EEG was recorded from 19 channels. Go and NoGo ERPs were
      decomposed using unrestricted Varimax-rotated PCAs for the groups separately, and
      in combination. The separate adult and child components were compared using the
      Congruence Coefficient. Brain sources of each assessed component were examined
      using eLORETA. RESULTS: Corresponding adult/child components were tentatively
      identified: two N1 subcomponents (N1-1, PN) and P2, followed by N2, P3 (separate
      P3a/P3b in children), the classic Slow Wave (SW), and a diffuse Late Positivity
      (LP). While early and late components showed similarities, the intermediate P2
      and N2 differed substantially in their stimulus effects. CONCLUSIONS: Aspects of
      "Go" vs. "NoGo" categorisation differ between adults and children, but subsequent
      processing reflected in the different Go/NoGo P3 components, and their sequellae,
      are similar. SIGNIFICANCE: This is the first detailed examination of child
      responses in this paradigm. The tested schema appears relatively robust in
      adults, and the child results may aid our understanding of developmental aspects
      of cognitive processing in normal and atypical individuals.

PMID- 24661625
TI  - Genetic variation of the greenhouse whitefly, Trialeurodes vaporariorum
      (Hemiptera: Aleyrodidae), among populations from Serbia and neighbouring
      countries, as inferred from COI sequence variability.
AB  - The greenhouse whitefly Trialeurodes vaporariorum Westwood, 1856 (Hemiptera:
      Aleyrodidae) is an invasive and highly polyphagous phloem-feeding pest of
      vegetables and ornamentals. Trialeurodes vaporariorum causes serious damage due
      to direct feeding and transmits several important plant viruses. Excessive use of
      insecticides has resulted in significantly reduced levels of susceptibility of
      various T. vaporariorum populations. To determine the genetic variability within
      and among populations of T. vaporariorum from Serbia and to explore their genetic
      relatedness with other T. vaporariorum populations, we analysed the mitochondrial
      cytochrome c oxidase I (COI) sequences of 16 populations from Serbia and six
      neighbouring countries: Montenegro (three populations), Macedonia (one
      population) and Croatia (two populations), for a total of 198 analysed specimens.
      A low overall level of sequence divergence and only five variable nucleotides and
      six haplotypes were found. The most frequent haplotype, H1, was identified in all
      Serbian populations and in all specimens from distant localities in Croatia and
      Macedonia. The COI sequence data that was retrieved from GenBank and the data
      from our study indicated that H1 is the most globally widespread T. vaporariorum
      haplotype. A lack of spatial genetic structure among the studied T. vaporariorum
      populations, as well as two demographic tests that we performed (Tajima's D value
      and Fu's Fs statistics), indicate a recent colonisation event and population
      growth. Phylogenetic analyses of the COI haplotypes in this study and other T.
      vaporariorum haplotypes that were retrieved from GenBank were performed using
      Bayesian inference and median-joining (MJ) network analysis. Two major
      haplogroups with only a single unique nucleotide difference were found:
      haplogroup 1 (containing the five Serbian haplotypes and those previously
      identified in India, China, the Netherlands, the United Kingdom, Morocco, Reunion
      and the USA) and haplogroup 3 (containing the single Serbian haplotype H3 and
      haplotypes from Costa Rica, the USA and Spanish Canary Islands). Collectively,
      our data indicate a rather limited value of COI as a genetic marker for
      discrimination between different T. vaporariorum populations in the investigated
      area. Possible explanations for the observed lack of COI sequence variability,
      such as specific genetics of biological invasion and/or the influence of
      bacterial symbionts that manipulate insect reproduction, are discussed. 

PMID- 24661626
TI  - Human pregnancy and generation of anti-angiotensin receptor and anti-perlecan
      antibodies.
AB  - Non-HLA antibodies against the angiotensin II type 1 receptor (AT1 R) and the C
      terminal fragment of perlecan (i.e., LG3) are associated with the development of
      renal allograft rejection. It is currently unknown how humans develop anti-AT1 R
      or anti-LG3 antibodies. The aim of this study was to investigate whether
      pregnancy-as a model of sensitization to polymorphic proteins-induces anti-AT1 R
      and/or anti-LG3 antibodies. We included 104 samples from women obtained after
      physiologic full-term pregnancy and 80 samples from healthy nonsensitized
      controls (40 women and 40 men). Both anti-AT1 R and anti-LG3 antibody levels were
      lower in pregnancy samples than in controls (both P < 0.05). By multivariate
      analysis, male gender was an independent predictor for high anti-AT1 R antibody
      levels (OR 3.66, P = 0.04) and pregnancy was predictive for low anti-LG3 antibody
      levels (OR 6.53, P = 0.0001). There was no correlation of anti-AT1 R with anti
      LG3 antibody levels, either in the pregnancy or in the control samples (r(2) <=
      0.03, P >= 0.26). In conclusion, physiologic full-term pregnancy does not induce
      anti-AT1 R or anti-LG3 antibodies and may even lower their levels. Therefore,
      anti-AT1 R and anti-LG3 antibodies are likely not caused by allosensitization.
      The lack of correlation of anti-AT1 R with anti-LG3 antibodies suggests different
      mechanisms of generation, which remain to be elucidated.

PMID- 24661624
TI  - Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2
      through an AtxA-dependent mechanism.
AB  - BACKGROUND: Upon infection of a mammalian host, Bacillus anthracis responds to
      host cues, and particularly to elevated temperature (37 degrees C) and
      bicarbonate/CO2 concentrations, with increased expression of virulence factors
      that include the anthrax toxins and extracellular capsular layer. This response
      requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator
      AtxA. To better understand the genetic basis of this response, we utilized a
      controlled in vitro system and Next Generation sequencing to determine and
      compare RNA expression profiles of the parental strain and an isogenic AtxA
      deficient strain in a 2 * 2 factorial design with growth environments containing
      or lacking carbon dioxide. RESULTS: We found 15 pXO1-encoded genes and 3
      chromosomal genes that were strongly regulated by the separate or synergistic
      actions of AtxA and carbon dioxide. The majority of the regulated genes responded
      to both AtxA and carbon dioxide rather than to just one of these factors.
      Interestingly, we identified two previously unrecognized small RNAs that are
      highly expressed under physiological carbon dioxide concentrations in an AtxA
      dependent manner. Expression levels of the two small RNAs were found to be higher
      than that of any other gene differentially expressed in response to these
      conditions. Secondary structure and small RNA-mRNA binding predictions for the
      two small RNAs suggest that they may perform important functions in regulating B.
      anthracis virulence. CONCLUSIONS: A majority of genes on the virulence plasmid
      pXO1 that are regulated by the presence of either CO2 or AtxA separately are also
      regulated synergistically in the presence of both. These results also elucidate
      novel pXO1-encoded small RNAs that are associated with virulence conditions.

PMID- 24661627
TI  - Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in
      patients with allergic rhinitis and asthma.
AB  - BACKGROUND: Myeloid dendritic cells (mDCs) and costimulatory molecules such as
      ICOSL/B7H2 play a pivotal role in murine experimental asthma, while little is
      known in human allergic disease. The aim of this study was to characterize the
      phenotype and ICOSL expression of mDCs from allergic rhinitis patients (AR) and
      their functional correlates on mDC regulation of T cell responses. METHODS: Human
      blood myeloid, CD1c(+) DCs were isolated from AR or healthy controls. Expression
      of costimulatory molecules inducible costimulatory ligand (ICOSL) and programmed
      death ligand 1 (PD-L1) was analysed in blood mDCs by flow cytometry and in nasal
      tissue biopsies by dual immunostaining. Blood mDCs were cocultured with
      (allogeneic) CD4(+) T cells before immunoassays for cytokine responses. RESULTS:
      mDCs from AR patients expressed a lower level of ICOSL, in both blood and nasal
      tissue. mDCs from AR were constitutively primed to induce Th2 cytokines and TNF
      in allogeneic CD4(+) T cells, while no difference was observed for IFN-gamma or
      IL-10. Production of IL-10 and IL-12 did not differ between AR and control mDCs.
      Blockade of ICOSL in control DCs up-regulated IL-13 but not IFN-gamma in
      cocultures with T cells, while PD-L1 blockade up-regulated both IL-13 and IFN
      gamma. CONCLUSIONS: Our data show that mDCs from patients with AR display
      impaired expression of ICOSL, and this defect licenses mDCs to promote aberrant
      IL-13- and IL-5-producing Th2 cell responses.

PMID- 24661629
TI  - Decreased frequency, but normal functional integrity of mesenchymal stromal cells
      derived from untreated and Imatinib-treated chronic myeloid leukemia patients.
AB  - In vitro, Imatinib inhibits the proliferation and stimulates the osteogenic and
      adipogenic differentiation of mesenchymal stromal cells (MSC). However, it is
      unknown whether Imatinib affects the biology of MSC in vivo. We asked whether MSC
      from long-term Imatinib-treated CML patients were affected by the in vivo
      treatment. MSC from untreated and Imatinib-treated patients displayed normal
      functional properties (i.e. proliferation, immunophenotype, differentiation and
      hematopoietic supportive capacity) - but a decreased frequency. In vitro,
      Imatinib lost its effect when discontinued; which suggest that it has a
      reversible effect on MSC. Therefore it might lose its effect on MSC after
      discontinuation in vivo. 

PMID- 24661628
TI  - Diabetic gastrointestinal motility disorders and the role of enteric nervous
      system: current status and future directions.
AB  - BACKGROUND: Gastrointestinal manifestations of diabetes are common and a source
      of significant discomfort and disability. Diabetes affects almost every part of
      gastrointestinal tract from the esophagus to the rectum and causes a variety of
      symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and
      constipation. Understanding the underlying mechanisms of diabetic
      gastroenteropathy is important to guide development of therapies for this common
      problem. Over recent years, the data regarding the pathophysiology of diabetic
      gastroenteropathy is expanding. In addition to autonomic neuropathy causing
      gastrointestinal disturbances the role of enteric nervous system is becoming more
      evident. PURPOSE: In this review, we summarize the reported alterations in
      enteric nervous system including enteric neurons, interstitial cells of Cajal and
      neurotransmission in diabetic animal models and patients. We also review the
      possible underlying mechanisms of these alterations, with focus on oxidative
      stress, growth factors and diabetes induced changes in gastrointestinal smooth
      muscle. Finally, we will discuss recent advances and potential areas for future
      research related to diabetes and the ENS such as gut microbiota, micro-RNAs and
      changes in the microvasculature and endothelial dysfunction.

PMID- 24661630
TI  - Adequate iron chelation therapy for at least six months improves survival in
      transfusion-dependent patients with lower risk myelodysplastic syndromes.
AB  - BACKGROUND: Most patients with myelodysplastic syndromes (MDS) require
      transfusions at the risk of iron overload and associated organ damage, and death.
      Emerging evidence indicates that iron chelation therapy (ICT) could reduce
      mortality and improve survival in transfusion-dependent MDS patients, especially
      those classified as International Prognostic Scoring System (IPSS) Low or
      Intermediate-1 (Low/Int-1). METHODS: Follow-up of a retrospective study. Sample
      included 127 Low/Int-1 MDS patients from 28 centers in Belgium. Statistical
      analysis stratified by duration (>=6 versus <6 months) and quality of chelation
      (adequate versus weak). RESULTS: Crude chelation rate was 63% but 88% among
      patients with serum ferritin >=1000 MUg/L. Of the 80 chelated patients, 70% were
      chelated adequately mainly with deferasirox (26%) or deferasirox following
      deferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32%
      among patients chelated >=6 m, and 30% among patients chelated adequately; with a
      trend toward reduced cardiac mortality in chelated patients. Overall, median
      overall survival (OS) was 10.2 years for chelated and 3.1 years for non-chelated
      patients (p<0.001). For patients chelated >=6 m or patients classified as
      adequately chelated, median OS was 10.5 years. Mortality increased as a function
      of average monthly transfusion intensity (HR=1.08, p=0.04) but was lower in
      patients receiving adequate chelation or chelation >=6 m (HR=0.24, p<0.001).
      CONCLUSION: Six or more months of adequate ICT is associated with markedly better
      overall survival. This suggests a possible survival benefit of ICT in transfusion
      dependent patients with lower-risk MDS.

PMID- 24661631
TI  - On the origin of the Norwegian lemming.
AB  - The Pleistocene glacial cycles resulted in significant changes in species
      distributions, and it has been discussed whether this caused increased rates of
      population divergence and speciation. One species that is likely to have evolved
      during the Pleistocene is the Norwegian lemming (Lemmus lemmus). However, the
      origin of this species, both in terms of when and from what ancestral taxon it
      evolved, has been difficult to ascertain. Here, we use ancient DNA recovered from
      lemming remains from a series of Late Pleistocene and Holocene sites to explore
      the species' evolutionary history. The results revealed considerable genetic
      differentiation between glacial and contemporary samples. Moreover, the analyses
      provided strong support for a divergence time prior to the Last Glacial Maximum
      (LGM), therefore likely ruling out a postglacial colonization of Scandinavia.
      Consequently, it appears that the Norwegian lemming evolved from a small
      population that survived the LGM in an ice-free Scandinavian refugium. 

PMID- 24661632
TI  - Acetylcholinesterase inhibitory activity and molecular docking study of 1-nitro-2
      phenylethane, the main constituent of Aniba canelilla essential oil.
AB  - The odoriferous principle of Aniba canelilla (H.B.K.) Mez is due 1-nitro-2
      phenylethane, the main constituent of its essential oil and also responsible for
      the plant's cinnamon scent. This nitroderivative was previously reported by their
      antioxidant, antinociception, cardiovascular, and vasorelaxant properties, and
      now it was tested as the inhibitor of acetylcholinesterase using bioautography on
      TLC plates. The oil and a purified fraction containing 1-nitro-2-phenylethane
      were analyzed by GC and GC-MS. The percentage content of 1-nitro-2-phenylethane
      in the oil and after fractionation was 70.2% and 98.0%, respectively. The results
      showed that the oil and 1-nitro-2-phenylethane are strong acetylcholinesterase
      inhibitors with the detection limit of 0.01 ng, equivalent to physostigmine used
      as the positive control. A molecular docking study was used to determine the
      position and conformation of the 1-nitro-2-phenylethane inhibitor in the receptor
      binding pocket of the acetylcholinesterase enzyme. The nitrogroup of 1-nitro-2
      phenylethane was positioned near of the catalytic serine residue of
      acetylcholinesterase, forming strong hydrogen bond with its hydroxyl group.
      Therefore, the electronegative character of 1-nitro-2-phenylethane may explain
      the interaction that occurs with the catalytic serine residue and its significant
      inhibitory activity of acetylcholinesterase. 

PMID- 24661633
TI  - Umbilical cord mesenchymal stem cell transplantation in active and refractory
      systemic lupus erythematosus: a multicenter clinical study.
AB  - INTRODUCTION: In our present single-center pilot study, umbilical cord (UC)
      derived mesenchymal stem cells (MSCs) had a good safety profile and therapeutic
      effect in severe and refractory systemic lupus erythematosus (SLE). The present
      multicenter clinical trial was undertaken to assess the safety and efficacy of
      allogeneic UC MSC transplantation (MSCT) in patients with active and refractory
      SLE. METHODS: Forty patients with active SLE were recruited from four clinical
      centers in China. Allogeneic UC MSCs were infused intravenously on days 0 and 7.
      The primary endpoints were safety profiles. The secondary endpoints included
      major clinical response (MCR), partial clinical response (PCR) and relapse.
      Clinical indices, including Systemic Lupus Erythematosus Disease Activity Index
      (SLEDAI) score, British Isles Lupus Assessment Group (BILAG) score and renal
      functional indices, were also taken into account. RESULTS: The overall survival
      rate was 92.5% (37 of 40 patients). UC-MSCT was well tolerated, and no
      transplantation-related adverse events were observed. Thirteen and eleven
      patients achieved MCR (13 of 40, 32.5%) and PCR (11 of 40, 27.5%), respectively,
      during 12 months of follow up. Three and four patients experienced disease
      relapse at 9 months (12.5%) and 12 months (16.7%) of follow-up, respectively,
      after a prior clinical response. SLEDAI scores significantly decreased at 3, 6, 9
      and 12 months follow-up. Total BILAG scores markedly decreased at 3 months and
      continued to decrease at subsequent follow-up visits. BILAG scores for renal,
      hematopoietic and cutaneous systems significantly improved. Among those patients
      with lupus nephritis, 24-hour proteinuria declined after transplantation, with
      statistically differences at 9 and 12 months. Serum creatinine and urea nitrogen
      decreased to the lowest level at 6 months, but these values slightly increased at
      9 and 12 months in seven relapse cases. In addition, serum levels of albumin and
      complement 3 increased after MSCT, peaked at 6 months and then slightly declined
      by the 9- and 12-month follow-up examinations. Serum antinuclear antibody and
      anti-double-stranded DNA antibody decreased after MSCT, with statistically
      significant differences at 3-month follow-up examinations. CONCLUSION: UC-MSCT
      results in satisfactory clinical response in SLE patients. However, in our
      present study, several patients experienced disease relapse after 6 months,
      indicating the necessity to repeat MSCT after 6 months. TRIAL REGISTRY:
      ClinicalTrials.gov identifier: NCT01741857. Registered 26 September 2012.

PMID- 24661634
TI  - Efficacy of biologically guided implant site preparation to obtain adequate
      primary implant stability.
AB  - The primary stability of dental implants is essentially influenced by the quality
      and quantity of hosting bone. To study the effects of adaptation of the drilling
      protocol to the biological quality of bone estimated by bone density and
      cortical/cancellous bone ratio, 8.5mm-short implants were placed in different
      bone types by adapting the drilling protocol to result in a socket under
      preparation by 0.2, 0.4, 0.7, 1 and 1.2mm in bone types I, II, III, IV and V,
      respectively. The effect of the drilling protocol was studied on implant
      insertion torque and osseointegration. Additionally, we analyzed the relationship
      of demographic data and social habits to bone type and insertion torque. Then the
      correlation between insertion torque and bone quality was tested. One hundred
      ninety two patients (mean age: 62 +/- 11 years) participated with 295 implants.
      The most common bone type at implant site was type III (47.1%) followed by type
      II (28.1%). Data analysis indicated that gender, age, and social habits had
      neither correlation with bone type nor with insertion torque. The insertion
      torque was 59.29 +/- 7.27 Ncm for bone type I, 56.51 +/- 1.62 Ncm for bone type
      II, 46.40 +/- 1.60 Ncm for bone type III, 34.84 +/- 2.38 Ncm for bone type IV and
      5 Ncm for bone type V. Statistically significant correlation was found between
      bone type and insertion torque. The followed drilling protocol adapts socket
      under-preparation to the needs of establishing a sufficient primary stability for
      implant osseointegration.

PMID- 24661635
TI  - Two elderly cases of familial mediterranean fever with rheumatoid arthritis.
AB  - Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder that
      usually develops before 20 years of age and is characterized by periodic fever
      with serositis and arthritis. Both FMF and rheumatoid arthritis (RA) involve
      arthritis; however, their coexistence is rare. We describe two RA patients with
      an MEFV mutation in exon 2, who were diagnosed with FMF at an age of over 50
      years. We also discuss the possibility that MEFV mutations could modulate RA
      disease activity.

PMID- 24661637
TI  - Prison health as public health in Afghanistan? A policy analysis of the on-going
      reform process.

PMID- 24661636
TI  - Multimodal approach for diagnosis of bacterial etiology in brain abscess.
AB  - BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy (PMRS) has high
      sensitivity and specificity for the detection of pyogenic brain abscess and the
      categorization of bacteria. But the metabolite patterns failed to evaluate the
      etiology of disease when the culture results are sterile. The aim of the present
      study is to compare the multimodality techniques viz., conventional culture, MR
      spectroscopy and 16S rRNA PCR and sequencing for rapid diagnosis of etiology in
      brain abscess and evaluate the PMRS in culture sterile samples and also
      demonstrate the sensitivity and specificity of these techniques. METHODS: Thirty
      five patients underwent MRI on a 3T MRI and in-vivo PMRS for the diagnosis and
      evaluation of various resonances of metabolites such as lipid (LIP), lactate
      (LAC), acetate (AC), amino acid (AC), succinate (SUC). Pus was collected for
      identification of etiologic agents by culture and molecular method. RESULTS: In
      35 samples, metabolite patterns were as follows: LIP/LAC/AA, n=17, LIP/LAC/AA/SUC
      with or without AC, n=17 and LIP/LAC/AA/AC, n=1. Culture showed bacterial growth
      in 22 samples (18 aerobic/facultative anaerobic, 9 anaerobic) whereas molecular
      method was detected 26 aerobic/facultative anaerobic, 13 anaerobic, 4
      microaerophilic bacteria. Among the 13 sterile samples, molecular method detected
      16 microorganisms along with 3 mixed infections and PMRS recognized metabolite
      patterns as LIP/LAC/AA, n= 5 and LIP/LAC/AA/SUC with or without AC, n=8. The
      sensitivity of in-vivo PMRS in sterile samples was 100% and 75%, and specificity
      was 75% and 100% for aerobic and anaerobic organisms respectively. CONCLUSION:
      Based on metabolite resonances, PMRS can detect slow growing and fastidious
      organisms and classify them into aerobic and anaerobic bacteria which are
      difficult to culture by conventional method. It can categorize microorganisms
      even in culture sterile samples with rational sensitivity and specificity which
      may allow early choice of targeted therapy.

PMID- 24661638
TI  - Women's education level, contraceptive use and maternal mortality estimates.

PMID- 24661639
TI  - Robotic nephroureterectomy: a simplified approach requiring no patient
      repositioning or robot redocking.
AB  - BACKGROUND: Robotic technology is increasingly adopted in urologic surgery and a
      variety of techniques has been described for minimally invasive treatment of
      upper tract urothelial cancer (UTUC). OBJECTIVE: To describe a simplified
      surgical technique of robot-assisted nephroureterectomy (RANU) and to report our
      single-center surgical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Patients with
      history of UTUC treated with this modality between April 2010 and August 2013
      were included in the analysis. Institutional review board approval was obtained.
      Informed consent was signed by all patients. SURGICAL PROCEDURE: A simplified
      single-step RANU not requiring repositioning or robot redocking. Lymph node
      dissection was performed selectively. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Descriptive analysis of patients' characteristics, perioperative
      outcomes, histopathology, and short-term follow-up data was performed. RESULTS
      AND LIMITATIONS: The analysis included 31 patients (mean age: 72.4+/-10.6 yr;
      mean body mass index: 26.6+/-5.1kg/m(2)). Twenty-six of 30 tumors (86%) were high
      grade. Mean tumor size was 3.1+/-1.8cm. Of the 31 patients, 13 (42%) had pT3
      stage disease. One periureteric positive margin was noted in a patient with bulky
      T3 disease. The mean number of lymph nodes removed was 9.4 (standard deviation:
      5.6; range: 3-21). Two of 14 patients (14%) had positive lymph nodes on final
      histology. No patients required a blood transfusion. Six patients experienced
      complications postoperatively, with only one being a high grade (Clavien 3b)
      complication. Median hospital stay was 5 d. Within the follow-up period, seven
      patients experienced bladder recurrences and four patients developed metastatic
      disease. CONCLUSIONS: Our RANU technique eliminates the need for patient
      repositioning or robot redocking. This technique can be safely reproduced, with
      surgical outcomes comparable to other established techniques. PATIENT SUMMARY: We
      describe a surgical technique using the da Vinci robot for a minimally invasive
      treatment of patients presenting with upper tract urothelial cancer. This
      technique can be safely implemented with good surgical outcomes.

PMID- 24661640
TI  - Computing limits on medicine risks based on collections of individual case
      reports.
AB  - BACKGROUND: Quantifying a medicine's risks for adverse effects is crucial in
      assessing its value as a therapeutic agent. Rare adverse effects are often not
      detected until after the medicine is marketed and used in large and heterogeneous
      patient populations, and risk quantification is even more difficult. While
      individual case reports of suspected harm from medicines are instrumental in the
      detection of previously unknown adverse effects, they are currently not used for
      risk quantification. The aim of this article is to demonstrate how and when
      limits on medicine risks can be computed from collections of individual case
      reports. METHODS: We propose a model where drug exposures in the real world may
      be followed by adverse episodes, each containing one or several adverse effects.
      Any adverse episode can be reported at most once, and each report corresponds to
      a single adverse episode. Based on this model, we derive upper and lower limits
      for the per-exposure risk of an adverse effect for a given drug. RESULTS: An
      upper limit for the per-exposure risk of the adverse effect Y for a given drug X
      is provided by the reporting ratio of X together with Y relative to all reports
      on X, under two assumptions: (i) the average number of adverse episodes following
      exposure to X is one or less; and (ii) adverse episodes that follow X and contain
      Y are more frequently reported than adverse episodes in general that follow X.
      Further, a lower risk limit is provided by dividing the number of reports on X
      together with Y by the total number of exposures to X, under the assumption that
      exposures to X that are followed by Y generate on average at most one report on X
      together with Y. Using real data, limits for the narcolepsy risk following
      Pandemrix vaccination and the risk of coeliac disease following antihypertensive
      treatment were computed and found to conform to reference risk values from
      epidemiological studies. CONCLUSIONS: Our framework enables quantification of
      medicine risks in situations where this is otherwise difficult or impossible. It
      has wide applicability, but should be particularly useful in structured benefit
      risk assessments that include rare adverse effects.

PMID- 24661641
TI  - Disaster resilience in tertiary hospitals: a cross-sectional survey in Shandong
      Province, China.
AB  - BACKGROUND: Hospital disaster resilience can be defined as a hospital's ability
      to resist, absorb, and respond to the shock of disasters while maintaining
      critical functions, and then to recover to its original state or adapt to a new
      one. This study aims to explore the status of resilience among tertiary hospitals
      in Shandong Province, China. METHODS: A stratified random sample (n = 50) was
      derived from tertiary A, tertiary B, and tertiary C hospitals in Shandong
      Province, and was surveyed by questionnaire. Data on hospital characteristics and
      8 key domains of hospital resilience were collected and analysed. Variables were
      binary, and analysed using descriptive statistics such as frequencies. RESULTS: A
      response rate of 82% (n = 41) was attained. Factor analysis identified four key
      factors from eight domains which appear to reflect the overall level of disaster
      resilience. These were hospital safety, disaster management mechanisms, disaster
      resources and disaster medical care capability. The survey demonstrated that in
      regard to hospital safety, 93% had syndromic surveillance systems for infectious
      diseases and 68% had evaluated their safety standards. In regard to disaster
      management mechanisms, all had general plans, while only 20% had specific plans
      for individual hazards. 49% had a public communication protocol and 43.9%
      attended the local coordination meetings. In regard to disaster resources, 75.6%
      and 87.5% stockpiled emergency drugs and materials respectively, while less than
      a third (30%) had a signed Memorandum of Understanding with other hospitals to
      share these resources. Finally in regard to medical care, 66% could dispatch an
      on-site medical rescue team, but only 5% had a 'portable hospital' function and
      36.6% and 12% of the hospitals could surge their beds and staff capacity
      respectively. The average beds surge capacity within 1 day was 13%. CONCLUSIONS:
      This study validated the broad utility of a framework for understanding and
      measuring the level of hospital resilience. The survey demonstrated considerable
      variability in disaster resilience arrangements of tertiary hospitals in Shandong
      province, and the difference between tertiary A hospitals and tertiary B
      hospitals was also identified in essential areas.

PMID- 24661642
TI  - High-performance thin layer chromatography to assess pharmaceutical product
      quality.
AB  - OBJECTIVE: To assess the sustainability, robustness and economic advantages of
      high-performance thin layer chromatography (HPTLC) for quality control of
      pharmaceutical products. METHOD: We compared three laboratories where three lots
      of cotrimoxazole tablets were assessed using different techniques for quantifying
      the active ingredient. RESULT: The average assay relative standard deviation for
      the three lots was 1.2 with a range of 0.65-2.0. CONCLUSION: High-performance
      thin layer chromatography assessments are yielding valid results suitable for
      assessing product quality. The local pharmaceutical manufacturer had evolved the
      capacity to produce very high quality products.

PMID- 24661643
TI  - Utility of inguinal incision in retroperitoneoscopic live donor nephrectomy.
AB  - BACKGROUND: Retroperitoneoscopic live donor nephrectomy has been performed in
      many countries. The purpose of this study was to evaluate the inguinal incision
      as a route for hand-assisted manipulation and allograft retrieval. METHODS: From
      April 2011 to June 2012, a prospective clinical study of 21 cases of
      retroperitoneal live donor nephrectomy was performed at our hospital. All donors
      were grouped in a test group (n = 11, inguinal incision) or a control group (n =
      10, lumbar incision). The operative time, warm ischaemia time, blood loss,
      hospital stay, cosmetic satisfaction, incision complications, and recipient's
      serum creatinines were compared between groups. RESULTS: All 21 cases of
      retroperitoneal live donor nephrectomy were accomplished successfully without
      serious complications. There was no difference in blood loss and operative time
      between groups. The mean warm ischaemic time and hospital stay was shorter (P <
      0.01), and satisfaction with cosmesis was greater (P < 0.05) in the test group.
      The abdominal asymmetry (4/10) and wound dehiscence occurred only in the control
      group. The recipient's serum creatinine was lower in the test group at 1 day (P <
      0.01) and 3 days (P < 0.05) after transplantation. CONCLUSION: The inguinal
      incision offers an ideal route for hand-assisted manipulation and allograft
      retrieval during retroperitoneoscopic live donor nephrectomy, and has a potential
      to be generally applied in the future.

PMID- 24661645
TI  - Effects of diabetes mellitus on amyotrophic lateral sclerosis: a systematic
      review.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable motor neuron
      degenerative disease which onset and course may be affected by concurrent
      diabetes mellitus (DM). We performed a systematic review to assess the effect of
      DM/dysglycemic states on ALS. METHODS: We searched PubMed MEDLINE, from inception
      to March 2013 for original articles published in English and in French languages
      on DM (and related states) and ALS. We made no restriction per study designs.
      RESULTS: Seven studies/1410 citations (5 case-control and 2 cross-sectional) were
      included in the final selection. The number of participants with ALS ranged from
      18 to 2371. The outcome of interest was ALS and DM/dysglycemic states
      respectively in three and two case control-studies. DM/impaired glucose tolerance
      status did not affect disease progression, survival, disease severity and disease
      duration in ALS participants but ALS participants with DM were found to be older
      in one study. DM/IGT prevalence was similar in both ALS and non ALS participants.
      This review was limited by the absence of prospective cohort studies and the
      heterogeneity in ALS and DM diagnosis criteria. CONCLUSIONS: This systematic
      review suggests that evidences for the association of ALS and DM are rather
      limited and derived from cross-sectional studies. Prospective studies
      supplemented by ALS registries and animal studies are needed to better understand
      the relationship between both conditions.

PMID- 24661644
TI  - Implementing the new CARF wellness standards.
AB  - Our objectives in this article are to provide background and practical
      applications of the implementation of the new wellness standards developed by the
      Commission on Accreditation of Rehabilitation Facilities (CARF). The focus of
      rehabilitation in the stroke population ideally extends beyond maximizing
      functioning and prevention of further debilitation, by addressing wellness and
      the opportunity to create a healthy lifestyle. This concept has been recognized
      by CARF, which has included new wellness standards for stroke rehabilitation.
      This article provides a framework for implementing these standards and trends
      related to prevalence, incidence, and prevention of stroke. The Transtheoretical
      Model of Change, as described by James Prochaska, is discussed in relation to
      facilitating lifestyle changes in stroke patients in the rehabilitation setting.
      Additionally, the Six Dimensions of Wellness Model by Dr Bill Hettler is
      presented as a framework for developing a wellness tool. Finally, we discuss the
      development, barriers, and implementation of a wellness tool used at Madonna
      Rehabilitation Hospital to exemplify a tangible strategy to meet the new CARF
      standards. 

PMID- 24661646
TI  - Paternal effects correlate with female reproductive stimulation in the
      polyandrous ladybird Cheilomenes sexmaculata.
AB  - Components of male seminal fluids are known to stimulate fecundity and fertility
      in females of numerous insect species and paternal effects on offspring phenotype
      are also known, but no studies have yet demonstrated links between male effects
      on female reproduction and those on progeny phenotype. In separate laboratory
      experiments employing 10-day-old virgin females of Cheilomenes sexmaculata (F.),
      we varied male age and mating history to manipulate levels of male allomones and
      found that the magnitude of paternal effects on progeny phenotype was correlated
      with stimulation of female reproduction. Older virgin males remained in copula
      longer than younger ones, induced higher levels of female fecundity, and sired
      progeny that developed faster to yield heavier adults. When male age was held
      constant (13 days), egg fertility declined as a function of previous male
      copulations, progeny developmental times increased, and the adult weight of
      daughters declined. These results suggest that male epigenetic effects on progeny
      phenotype act in concert with female reproductive stimulation; both categories of
      effects increased as a consequence of male celibacy (factor accumulation), and
      diminished as a function of previous matings (factor depletion). Male factors
      that influence female reproduction are implicated in sexual conflict and parental
      effects may extend this conflict to offspring phenotype. Whereas mothers control
      the timing of oviposition events and can use maternal effects to tailor progeny
      phenotypes to prevailing or anticipated conditions, fathers cannot. Since females
      remate and dilute paternity in polyandrous systems, paternal fitness will be
      increased by linking paternal effects to female fecundity stimulation, so that
      more benefits accrue to the male's own progeny. 

PMID- 24661647
TI  - Epithelial function and dysfunction in asthma.
AB  - Asthma was previously defined as an allergic Th2-mediated inflammatory immune
      disorder. Recently, this paradigm has been challenged because not all
      pathological changes observed in the asthmatic airways are adequately explained
      simply as a result of Th2-mediated processes. Contemporary thought holds that
      asthma is a complex immune disorder involving innate as well as adaptive immune
      responses, with the clinical heterogeneity of asthma perhaps a result of the
      different relative contribution of these two systems to the disease.
      Epidemiological studies show that exposure to certain environmental substances is
      strongly associated with the risk of developing asthma. The airway epithelium is
      first barrier to interact with, and respond to, environmental agents (pollution,
      viral infection, allergens), suggesting that it is a key player in the pathology
      of asthma. Epithelial cells play a key role in the regulation of tissue
      homeostasis by the modulation of numerous molecules, from antioxidants and lipid
      mediators to growth factors, cytokines, and chemokines. Additionally, the
      epithelium is also able to suppress mechanisms involved in, for example,
      inflammation in order to maintain homeostasis. An intrinsic alteration or defect
      in these regulation mechanisms compromises the epithelial barrier, and therefore,
      the barrier may be more prone to environmental substances and thus more likely to
      exhibit an asthmatic phenotype. In support of this, polymorphisms in a number of
      genes that are expressed in the bronchial epithelium have been linked to asthma
      susceptibility, while environmental factors may affect epigenetic mechanisms that
      can alter epithelial function and response to environmental insults. A detailed
      understanding of the regulatory role of the airway epithelium is required to
      develop new therapeutic strategies for asthma that not only address the symptoms
      but also the underlining pathogenic mechanism(s) and prevent airway remodelling. 

PMID- 24661648
TI  - Symptom-based screening tool in ruling out active tuberculosis among HIV-infected
      patients eligible for isoniazid preventive therapy in Tanzania.
AB  - OBJECTIVES: We assessed the usefulness of the National TB and Leprosy Control
      Program (NTLP) symptom-based tuberculosis (TB) screening tool in identifying HIV
      infected patients eligible for isoniazid preventive therapy in Muhimbili National
      Hospital, Dar es Salaam Tanzania. METHODS: Descriptive cross-sectional study.
      Data collected included socio-demographic and clinical data. Chest X-ray, sputum
      for acid-fast bacilli (AFB) microscopy, mycobacterial culture, CD4 + count and
      complete blood count were performed. Patients were considered not having active
      TB if they presented with no symptom in the screening tool, which comprised these
      symptoms: cough, fever and excessive night sweats for >=2 weeks; weight loss of
      >=3 kg in 4 weeks and haemoptysis of any duration. The reference standard was a
      negative culture for Mycobacterium tuberculosis. RESULTS: We enroled 373
      patients, of whom 72.1% were females. Active pulmonary TB was found in 4.1%
      (14/338) of the participants as defined by a positive culture. The sensitivity
      and specificity of the NTLP screening tool were 71.4% (10/14) and 75.9%
      (246/324), respectively. False-negative rate was 28.6% (4/10). Cough, fever for
      >=2 weeks and weight loss were independent predictors of NTLP-defined TB. Cough
      >=2 weeks predicted TB when a positive culture was used to define TB. CONCLUSION:
      The screening tool had fairly good sensitivity and specificity for TB screening;
      however, there is a possibility that about 29% of the screened population will be
      given IPT while they are supposed to receive a full course of TB treatment.

PMID- 24661649
TI  - The Red Journal's outstanding reviewers of 2013.

PMID- 24661651
TI  - Outcomes of low-risk ductal carcinoma in situ in Southeast Asian women treated
      with breast conservation therapy.
AB  - PURPOSE: To examine the outcomes of Southeast Asian (SEA) women with low-risk
      ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and
      adjuvant radiation therapy. METHODS AND MATERIALS: Retrospective chart reviews of
      patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients
      meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were
      included. Most patients received adjuvant radiation therapy (RT) consisting of
      whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed.
      RESULTS: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273
      met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG),
      n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral
      breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated
      actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%,
      respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not.
      There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT.
      The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All
      patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5
      years, giving an estimated IBTR rate of 4.5% at 10 years. CONCLUSIONS: SEA women
      with screen-detected DCIS have exceedingly low rates of IBTR after BCS,
      comparable to that observed in reports of similar patients with low-risk DCIS
      treated with adjuvant radiation.

PMID- 24661650
TI  - Combinations of radiation therapy and immunotherapy for melanoma: a review of
      clinical outcomes.
AB  - Radiation therapy has long played a role in the management of melanoma. Recent
      advances have also demonstrated the efficacy of immunotherapy in the treatment of
      melanoma. Preclinical data suggest a biologic interaction between radiation
      therapy and immunotherapy. Several clinical studies corroborate these findings.
      This review will summarize the outcomes of studies reporting on patients with
      melanoma treated with a combination of radiation therapy and immunotherapy.
      Vaccine therapies often use irradiated melanoma cells, and may be enhanced by
      radiation therapy. The cytokines interferon-alpha and interleukin-2 have been
      combined with radiation therapy in several small studies, with some evidence
      suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody
      which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation
      therapy in several notable case studies and series. Finally, pilot studies of
      adoptive cell transfer have suggested that radiation therapy may improve the
      efficacy of treatment. The review will demonstrate that the combination of
      radiation therapy and immunotherapy has been reported in several notable case
      studies, series and clinical trials. These clinical results suggest interaction
      and the need for further study.

PMID- 24661652
TI  - Outcomes and patterns of failure for grade 2 meningioma treated with reduced
      margin intensity modulated radiation therapy.
AB  - PURPOSE: The purpose of this study was to evaluate intracranial control and
      patterns of local recurrence (LR) for grade 2 meningiomas treated with intensity
      modulated radiation therapy (IMRT) with limited total margin expansions of <=1
      cm. METHODS AND MATERIALS: We reviewed records of patients with a
      neuropathological diagnosis of grade 2 meningioma who underwent IMRT at our
      institution between 2002 and 2012. Actuarial rates were determined by the Kaplan
      Meier method from the end of RT. LR was defined as in-field if >=90% of the
      recurrence was within the prescription isodose, out-of-field (marginal) if >=90%
      was outside of the prescription isodose, and both if neither criterion was met.
      RESULTS: Between 2002 and 2012, a total of 54 consecutive patients underwent IMRT
      for grade 2 meningioma. Eight of these patients had total initial margins >1 cm
      and were excluded, leaving 46 patients for analysis. The median imaging follow-up
      period was 26.2 months (range, 7-107 months). The median dose for fractionated
      IMRT was 59.4 Gy (range, 49.2-61.2 Gy). Median clinical target volume (CTV),
      planning target volume (PTV), and total margin expansion were 0.5 cm, 0.3 cm, and
      0.8 cm, respectively. LR occurred in 8 patients (17%), with 2-year and 3-year
      actuarial local control (LC) of 92% and 74%, respectively. Six of 8 patients
      (85%) had a known pattern of failure. Five patients (83%) had in-field LR; no
      patients had marginal LR; and 1 patient (17%) had both. CONCLUSIONS: The use of
      IMRT to treat grade 2 meningiomas with total initial margins (CTV + PTV) <=1 cm
      did not appear to compromise outcomes or increase marginal failures compared with
      other modern retrospective series. Of the 46 patients who had margins <=1 cm,
      none experienced marginal failure only. These results demonstrate efficacy and
      low risk of marginal failure after IMRT treatment of grade 2 meningiomas with
      reduced margins, warranting study within a prospective clinical trial.

PMID- 24661653
TI  - Long-term outcomes and complications in patients with craniopharyngioma: the
      British Columbia Cancer Agency experience.
AB  - PURPOSE: We report long-term outcomes and complications of craniopharyngioma
      patients referred to our institution. METHODS AND MATERIALS: Between 1971 and
      2010, 123 consecutive patients received primary treatment for craniopharyngioma
      in British Columbia and were referred to our institution. The median age was 30
      years (range, 2-80 years). Thirty-nine percent of patients were treated primarily
      with subtotal resection (STR) and radiation therapy (RT), 28% with STR alone, 15%
      with gross total resection, 11% with cyst drainage (CD) alone, 5% with CD+RT, and
      2% with RT alone. Eight percent of patients received intracystic bleomycin (ICB)
      therapy. RESULTS: Median follow-up was 8.9 years, and study endpoints were
      reported at 10 years. Ten-year Kaplan-Meier progression-free survival (PFS) was
      46%. Patients treated with STR+RT or CD+RT had the highest PFS (82% and 83%,
      respectively). There were no significant differences between PFS after adjuvant
      versus salvage RT (84% vs 74%, respectively; P=.6). Disease-specific survival
      (DSS) was 88%, and overall survival (OS) was 80%. Primary treatment modality did
      not affect DSS or OS, while older age was a negative prognostic factor for OS but
      not DSS. Kaplan-Meier rates for visual deterioration, anterior pituitary hormone
      deficiency, diabetes insipidus, seizure disorder, and cerebrovascular events
      (CVE) due to treatment, not tumor progression, were 27%, 76%, 45%, 16%, and 11%,
      respectively. The CVE rate was 29% in patients who received ICB compared to 10%
      in those who did not (P=.07). CONCLUSIONS: We report favorable PFS in patients
      with craniopharyngioma, especially in those who received RT after surgery. DSS
      and OS rates were excellent regardless of primary treatment modality. We observed
      a high incidence of hypopituitarism, visual deterioration, and seizure disorder.
      Eleven percent of patients experienced CVEs after treatment. There was a
      suggestion of increased CVE risk in patients treated with ICB.

PMID- 24661654
TI  - Postponed is not canceled: role of craniospinal radiation therapy in the
      management of recurrent infant medulloblastoma--an experience from the HIT-REZ
      1997 & 2005 studies.
AB  - PURPOSE: To evaluate the efficacy of craniospinal irradiation (CSI) in the
      management of recurrent infant medulloblastoma after surgery and chemotherapy
      alone. METHODS AND MATERIALS: Seventeen pediatric medulloblastoma patients
      registered in the HIT-REZ 1997 and 2005 studies underwent CSI as salvage
      treatment at first recurrence. All patients had achieved complete remission after
      first-line treatment consisting of surgery and chemotherapy. Eleven patients
      showed metastatic disease at relapse. Five patients underwent surgery prior to
      radiation therapy, which resulted in complete resection in 1 case. In 1 patient,
      complete resection of the residual tumor was performed after CSI. Eleven patients
      received chemotherapy prior, 6 patients during and 8 patients after CSI. All
      patients received CSI with a median total dose of 35.2 Gy, and all but 1 received
      a boost to the posterior fossa (median total dose, 55.0 Gy). Metastases were
      boosted with an individual radiation dose, depending on their location and
      extent. RESULTS: During a median follow-up time of 6.2 years since recurrence, 11
      patients showed progressive disease and died. Median progression-free (overall)
      survival was 2.9 +/- 1.1 (3.8 +/- 0.8) years. Progression-free survival (PFS)
      rates at 1, 3, and 5 years were 88% +/- 8%, 46% +/- 12%, and 40% +/- 12%,
      respectively. Overall survival (OS) rates at 1, 3, and 5 years were 94% +/- 6%,
      58% +/- 12%, and 39% +/- 12%, respectively. For 11 patients with classic
      medulloblastoma, 3-year (and 5-year) PFS and OS were 62% +/- 15% and 72% +/- 14%
      (52% +/- 16% and 51% +/- 16%), respectively. On univariate analysis, metastatic
      disease was not associated with poorer progression-free and overall survival.
      CONCLUSIONS: Our results suggest that salvage treatment of relapsed
      medulloblastomas consisting of CSI and chemotherapy offers a second chance for
      cure, even for patients with classic histological findings. Metastatic disease at
      relapse did not have an impact on survival. However, this may be explained by the
      small number of patients.

PMID- 24661655
TI  - Chemoradiation of hepatic malignancies: prospective, phase 1 study of full-dose
      capecitabine with escalating doses of yttrium-90 radioembolization.
AB  - PURPOSE: Radiosensitizing chemotherapy improves the outcomes in comparison with
      radiation alone for gastrointestinal cancers. The delivery of radiation therapy
      with yttrium90 ((90)Y) radioembolization, in combination with the
      radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to
      enhance the effects of radiation on hepatic malignancies. This phase 1 study
      sought to determine the maximum tolerated dose (MTD) of (90)Y plus capecitabine
      in patients with cholangiocarcinoma or liver metastases confined to the liver.
      METHODS AND MATERIALS: Patients were given initial treatment at full-dose
      capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second
      cycle, whole-liver (90)Y was given at the test dose, after which time
      capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks
      after (90)Y infusion. If a DLT was not observed, the (90)Y dose was escalated.
      The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was
      to determine the MTD of (90)Y with full-dose capecitabine. RESULTS: Sixteen
      patients were treated according to the study protocol. Two patients experienced
      DLTs. Nine patients required capecitabine dose reduction as a result of
      toxicities attributable to capecitabine alone. The criteria for establishing
      (90)Y MTD were not met, indicating an MTD of >170 Gy. CONCLUSION: The MTD of
      (90)Y delivered in conjunction with capecitabine in the setting of intrahepatic
      cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy.
      This is the highest (90)Y dose reported to date and has important implications on
      combined therapy with the radiosensitizing oral chemotherapeutic capecitabine.
      Further studies are under way.

PMID- 24661656
TI  - Intraoperative radiation therapy reduces local recurrence rates in patients with
      microscopically involved circumferential resection margins after resection of
      locally advanced rectal cancer.
AB  - PURPOSE: Intraoperative radiation therapy (IORT) is advocated by some for
      patients with locally advanced rectal cancer (LARC) who have involved or narrow
      circumferential resection margins (CRM) after rectal surgery. This study
      evaluates the potentially beneficial effect of IORT on local control. METHODS AND
      MATERIALS: All surgically treated patients with LARC treated in a tertiary
      referral center between 1996 and 2012 were analyzed retrospectively. The outcome
      in patients treated with IORT with a clear but narrow CRM (<=2 mm) or a
      microscopically involved CRM was compared with the outcome in patients who were
      not treated with IORT. RESULTS: A total of 409 patients underwent resection of
      LARC, and 95 patients (23%) had a CRM <= 2 mm. Four patients were excluded from
      further analysis because of a macroscopically involved resection margin. In 43
      patients with clear but narrow CRMs, there was no difference in the cumulative 5
      year local recurrence-free survival of patients treated with (n=21) or without
      (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved
      CRM, there was a significant difference in the cumulative 5-year local recurrence
      free survival in favor of the patients treated with IORT (n=31) compared with
      patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis
      confirmed that IORT was independently associated with a decreased local
      recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was
      no significant difference in complication rate of patients treated with or
      without IORT (65% vs 52%, P=.18) CONCLUSION: The current study suggests that IORT
      reduces local recurrence rates in patients with LARC with a microscopically
      involved CRM.

PMID- 24661657
TI  - Phase 2 study of combined sorafenib and radiation therapy in patients with
      advanced hepatocellular carcinoma.
AB  - PURPOSE: This phase 2 study evaluated the efficacy of radiation therapy (RT) with
      concurrent and sequential sorafenib therapy in patients with unresectable
      hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Forty patients with
      unresectable HCC unfit for transarterial chemoembolization were treated with RT
      with concurrent and sequential sorafenib. Sorafenib was administered from the
      commencement of RT at a dose of 400 mg twice daily and continued to clinical or
      radiologic progression, unacceptable adverse events, or death. All patients had
      underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm
      to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was
      irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy
      (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months
      thereafter. RESULTS: Thirty-three (83%) completed the allocated RT. During RT,
      the incidence of hand-foot skin reactions >= grade 2 and diarrhea were 37.5% and
      25%, respectively, and 35% of patients had hepatic toxicities grade >=2. Twenty
      two (55.0%) patients achieved complete or partial remission at the initial
      assessment, and 18 (45%) had stable or progressive disease. The 2-year overall
      survival and infield progression-free survival (IFPS) were 32% and 39%,
      respectively. A Cancer of the Liver Italian Program (CLIP) score >=2 was
      associated with an inferior outcome in overall survival. Six patients (15%)
      developed treatment-related hepatic toxicity grade >=3 during the sequential
      phase, and 3 of them were fatal. CONCLUSIONS: When RT and sorafenib therapy were
      combined in patients with unresectable HCC, the initial complete or partial
      response rate was 55% with a 2-year IFPS of 39%. A CLIP score >=2 was associated
      with an inferior outcome in overall survival. Hepatic toxicities are a major
      determinant of the safety; the combination should be used with caution and needs
      further investigation.

PMID- 24661658
TI  - Clinical-pathologic stage discrepancy in bladder cancer patients treated with
      radical cystectomy: results from the national cancer data base.
AB  - PURPOSE: To examine the accuracy of clinical staging and its effects on outcome
      in bladder cancer (BC) patients treated with radical cystectomy (RC), using a
      large national database. METHODS AND MATERIALS: A total of 16,953 patients with
      BC without distant metastases treated with RC from 1998 to 2009 were analyzed.
      Factors associated with clinical-pathologic stage discrepancy were assessed by
      multivariate generalized estimating equation models. Survival analysis was
      conducted for patients treated between 1998 and 2004 (n=7270) using the Kaplan
      Meier method and Cox proportional hazards models. RESULTS: At RC 41.9% of
      patients were upstaged, whereas 5.9% were downstaged. Upstaging was more common
      in females, the elderly, and in patients who underwent a more extensive
      lymphadenectomy. Downstaging was less common in patients treated at community
      centers, in the elderly, and in Hispanics. Receipt of preoperative chemotherapy
      was highly associated with downstaging. Five-year overall survival rates for
      patients with clinical stages 0, I, II, III, and IV were 67.2%, 62.9%, 50.4%,
      36.9%, and 27.2%, respectively, whereas those for the same pathologic stages were
      70.8%, 75.8%, 63.7%, 41.5%, and 24.7%, respectively. On multivariate analysis,
      upstaging was associated with increased 5-year mortality (hazard ratio [HR] 1.80,
      P<.001), but downstaging was not associated with survival (HR 0.88, P=.160). In
      contrast, more extensive lymphadenectomy was associated with decreased 5-year
      mortality (HR 0.76 for >=10 lymph nodes examined, P<.001), as was treatment at an
      National Cancer Institute-designated cancer center (HR 0.90, P=.042).
      CONCLUSIONS: Clinical-pathologic stage discrepancy in BC patients is remarkably
      common across the United States. These findings should be considered when
      selecting patients for preoperative or nonoperative management strategies and
      when comparing the outcomes of bladder sparing approaches to RC.

PMID- 24661659
TI  - Relationship between radiation-induced apoptosis of T lymphocytes and chronic
      toxicity in patients with prostate cancer treated by radiation therapy: a
      prospective study.
AB  - PURPOSE: To assess the correlation of radiation-induced apoptosis in vitro of CD4
      and CD8 T lymphocytes with late toxicity of prostate cancer patients treated with
      radiation therapy. METHODS AND MATERIALS: 214 patients were prospectively
      included in the study. Peripheral blood was drawn from patients before treatment
      and irradiated with 8 Gy. The percentage of CD4+ and CD8+ T lymphocytes that
      underwent radiation-induced apoptosis was assessed by flow cytometry. Toxicity
      and mortality were correlated in 198 cases with pretreatment apoptosis and
      clinical and biological variables by use of a Cox proportional hazards model.
      RESULTS: The mean percentage of CD4+ and CD8+ T lymphocyte radiation-induced
      apoptosis was 28.58% (+/-14.23) and 50.76% (+/-18.9), respectively. Genitourinary
      (GU) toxicity was experienced by 39.9% of patients, while gastrointestinal (GI)
      toxicity was experienced by 19.7%. The probability of development of GU toxicity
      was nearly doubled (hazard ratio [HR] 1.99, P=.014) in those patients in whom the
      percentage of in vitro radiation-induced apoptosis of CD4+ T-lymphocytes was
      <=28.58%. It was also almost double in patients who received doses >=50 Gy in 65%
      of the bladder volume (V65 >=50) (HR 1.92, P=.048). No correlation was found
      between GI toxicity and any of the variables studied. The probability of death
      during follow-up, after adjustment for different variables, was 2.7 times higher
      in patients with a percentage of CD8+ T lymphocyte apoptosis <=50.76% (P=.022).
      CONCLUSIONS: In conclusion, our study shows, in the largest prospective cohort of
      prostate cancer patients undergoing radiation therapy, that in vitro radiation
      induced apoptosis of CD4+ T lymphocytes assessed before radiation therapy was
      associated with the probability of developing chronic GU toxicity. In addition,
      the radiation dose received in the urinary bladder (V65 >=50) affected the
      occurrence of GU toxicity. Finally, we also demonstrate that radiation-induced
      apoptosis of CD8+ T lymphocytes was associated with overall survival, although
      larger series are needed to confirm this finding.

PMID- 24661660
TI  - The impact of definitive local therapy for lymph node-positive prostate cancer: a
      population-based study.
AB  - PURPOSE: To evaluate the survival outcomes for patients with lymph node-positive,
      nonmetastatic prostate cancer undergoing definitive local therapy (radical
      prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no
      local therapy (NLT) in the US population in the modern prostate specific antigen
      (PSA) era. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results
      database was queried for patients with T1-4N1M0 prostate cancer diagnosed from
      1995 through 2005. To allow comparisons of equivalent datasets, patients were
      analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node
      positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific
      survival (PCSS) estimates were generated, with accompanying univariate log-rank
      and multivariate Cox proportional hazards comparisons. RESULTS: A total of 796
      cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT
      and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of
      45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+
      patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had
      NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65%
      versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate
      analysis, local therapy in both the cN+ and pN+ cohorts remained independently
      associated with improved OS and PCSS (all P<.001). Local therapy was associated
      with favorable hazard ratios across subgroups, including patients aged >=70 years
      and those with multiple positive lymph nodes. Among pN+ patients, no significant
      differences in survival were observed between RP versus EBRT and RP with or
      without adjuvant EBRT. CONCLUSIONS: In this large, population-based cohort,
      definitive local therapy was associated with significantly improved survival in
      patients with lymph node-positive prostate cancer.

PMID- 24661661
TI  - Risk of late toxicity in men receiving dose-escalated hypofractionated intensity
      modulated prostate radiation therapy: results from a randomized trial.
AB  - OBJECTIVE: To report late toxicity outcomes from a randomized trial comparing
      conventional and hypofractionated prostate radiation therapy and to identify
      dosimetric and clinical parameters associated with late toxicity after
      hypofractionated treatment. METHODS AND MATERIALS: Men with localized prostate
      cancer were enrolled in a trial that randomized men to either conventionally
      fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy
      fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy
      fractions). Late (>=90 days after completion of radiation therapy) genitourinary
      (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored
      according to modified Radiation Therapy Oncology Group criteria. RESULTS: 101 men
      received CIMRT and 102 men received HIMRT. The median age was 68, and the median
      follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had
      intermediate-risk, and 1% had high-risk disease. There was no difference in late
      GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade >=2
      GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a
      nonsignificant numeric increase in late GI toxicity in men treated with HIMRT
      compared with men treated with CIMRT. The actuarial 5-year grade >=2 GI toxicity
      was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the
      proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was
      associated with the development of late GI toxicity (P<.05). The 5-year actuarial
      grade >=2 GI toxicity was 27.3% in men with R64.6Gy >= 20% but only 6.0% in men
      with R64.6Gy < 20% (P=.016). CONCLUSIONS: Dose-escalated IMRT using a moderate
      hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely
      with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that
      receives moderate and high dose decreases the risk of late rectal toxicity after
      this hypofractionation regimen.

PMID- 24661662
TI  - Outcomes and toxicity for hypofractionated and single-fraction image-guided
      stereotactic radiosurgery for sarcomas metastasizing to the spine.
AB  - PURPOSE: Conventional radiation treatment (20-40 Gy in 5-20 fractions, 2-5 Gy per
      fraction) for sarcoma metastatic to the spine provides subtherapeutic doses,
      resulting in poor durable local control (LC) (50%-77% at 1 year).
      Hypofractionated (HF) and/or single-fraction (SF) image-guided stereotactic
      radiosurgery (IG-SRS) may provide a more effective means of managing these
      lesions. METHODS AND MATERIALS: Patients with pathologically proven high-grade
      sarcoma metastatic to the spine treated with HF and SF IG-SRS were included. LC
      and overall survival (OS) were analyzed by the use of Kaplan-Meier statistics.
      Univariate and multivariate analyses were performed by the use of Cox regression
      with competing-risks analysis; all confidence intervals are 95%. Toxicities were
      assessed according to Common Terminology Criteria for Adverse Events, version
      4.0. RESULTS: From May 2005 to November 11, 2012, 88 patients with 120 discrete
      metastases received HF (3-6 fractions; median dose, 28.5 Gy; n=52, 43.3%) or SF
      IG-SRS (median dose, 24 Gy; n=68, 56.7%). The median follow-up time was 12.3
      months. At 12 months, LC was 87.9% (confidence interval [CI], 81.3%-94.5%), OS
      was 60.6% (CI, 49.6%-71.6%), and median survival was 16.9 months. SF IG-SRS
      demonstrated superior LC to HF IG-SRS (12-month LC of 90.8% [CI, 83%-98.6%] vs
      84.1% [CI, 72.9%-95.3%] P=.007) and retained significance on multivariate
      analysis (P=.030, hazard ratio 0.345; CI, 0.132-0.901]. Treatment was well
      tolerated, with 1% acute grade 3 toxicity, 4.5% chronic grade 3 toxicity, and no
      grade >3 toxicities. CONCLUSIONS: In the largest series of metastatic sarcoma to
      the spine to date, IG-SRS provides excellent LC in the setting of an aggressive
      disease with low radiation sensitivity and poor prognosis. Single-fraction IG-SRS
      is associated with the highest rates of LC with minimal toxicity.

PMID- 24661663
TI  - No clinically significant changes in pulmonary function following stereotactic
      body radiation therapy for early- stage peripheral non-small cell lung cancer: an
      analysis of RTOG 0236.
AB  - PURPOSE: To investigate pulmonary function test (PFT) results and arterial blood
      gas changes (complete PFT) following stereotactic body radiation therapy (SBRT)
      and to see whether baseline PFT correlates with lung toxicity and overall
      survival in medically inoperable patients receiving SBRT for early stage,
      peripheral, non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: During the
      2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral
      NSCLC who received effectively 18 Gy * 3 in a phase 2 North American multicenter
      study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity
      was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon
      signed rank test, logistic regression model, and Kaplan-Meier method were used
      for statistical analysis. RESULTS: At 2 years, mean percentage predicted forced
      expiratory volume in the first second and diffusing capacity for carbon monoxide
      declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood
      gases and no significant decline in oxygen saturation. Baseline PFT was not
      predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the
      percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the
      whole lung were almost identical between patients who developed pneumonitis and
      patients who were pneumonitis-free. Poor baseline PFT did not predict decreased
      overall survival. Patients with poor baseline PFT as the reason for medical
      inoperability had higher median and overall survival rates than patients with
      normal baseline PFT values but with cardiac morbidity. CONCLUSIONS: Poor baseline
      PFT did not appear to predict pulmonary toxicity or decreased overall survival
      after SBRT in this medically inoperable population. Poor baseline PFT alone
      should not be used to exclude patients with early stage lung cancer from
      treatment with SBRT.

PMID- 24661664
TI  - Stereotactic body radiation therapy for re-irradiation of persistent or recurrent
      non-small cell lung cancer.
AB  - PURPOSE: To retrospectively assess toxicity and outcome of re-irradiation with
      stereotactic body radiation therapy (SBRT) in patients with recurrent or
      persistent non-small cell lung cancer (NSCLC), who were previously treated with
      radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate
      whether there are dosimetric parameter predictors of severe radiation toxicity.
      METHODS AND MATERIALS: The analysis was conducted in 17 patients with "in-field"
      recurrent/persistent centrally located NSCLC, who underwent re-irradiation with
      SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be
      equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction
      cumulative dose to 87 to 100 Gy, considering the primary radiation therapy
      treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier
      method, and P values were estimated by the log-rank test, starting from the date
      of completion of SBRT. Dosimetric parameters from the subgroups with and without
      grade >=3 pulmonary toxicity were compared using a 2-tailed Student t test.
      RESULTS: The median follow-up was 18 months (range, 4-57 months). Only 2 patients
      had local failure, corresponding to a local control rate of 86% at 1 year. The
      Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59%
      and 29%, respectively; the median OS was 19 months. Four patients (23%)
      experienced grade 3 radiation pneumonitis, and 1 patient developed fatal
      pneumonitis. One patient died of fatal hemoptysis 2 months after the completion
      of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the
      heart volume), and D10 were correlated with risk of radiation pneumonitis
      (P<.05). CONCLUSIONS: Re-irradiation with SBRT for recurrent/persistent centrally
      located NSCLC achieves excellent results in terms of local control. However, the
      high rate of severe toxicity reported in our study is of concern.

PMID- 24661665
TI  - Stereotactic ablative radiation therapy for centrally located early stage or
      isolated parenchymal recurrences of non-small cell lung cancer: how to fly in a
      "no fly zone".
AB  - PURPOSE: We extended our previous experience with stereotactic ablative radiation
      therapy (SABR; 50 Gy in 4 fractions) for centrally located non-small cell lung
      cancer (NSCLC); explored the use of 70 Gy in 10 fractions for cases in which dose
      volume constraints could not be met with the previous regimen; and suggested
      modified dose-volume constraints. METHODS AND MATERIALS: Four-dimensional
      computed tomography (4DCT)-based volumetric image-guided SABR was used for 100
      patients with biopsy-proven, central T1-T2N0M0 (n=81) or isolated parenchymal
      recurrence of NSCLC (n=19). All disease was staged with positron emission
      tomography/CT; all tumors were within 2 cm of the bronchial tree, trachea, major
      vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body.
      Endpoints were toxicity, overall survival (OS), local and regional control, and
      distant metastasis. RESULTS: At a median follow-up time of 30.6 months, median OS
      time was 55.6 months, and the 3-year OS rate was 70.5%. Three-year cumulative
      actuarial local, regional, and distant control rates were 96.5%, 87.9%, and
      77.2%, respectively. The most common toxicities were chest-wall pain (18% grade
      1, 13% grade 2) and radiation pneumonitis (11% grade 2 and 1% grade 3). No
      patient experienced grade 4 or 5 toxicity. Among the 82 patients receiving 50 Gy
      in 4 fractions, multivariate analyses showed mean total lung dose >6 Gy, V20
      >12%, or ipsilateral lung V30 >15% to independently predict radiation
      pneumonitis; and 3 of 9 patients with brachial plexus Dmax >35 Gy experienced
      brachial neuropathy versus none of 73 patients with brachial Dmax <35 Gy
      (P=.001). Other toxicities were analyzed and new dose-volume constraints are
      proposed. CONCLUSIONS: SABR for centrally located lesions produces clinical
      outcomes similar to those for peripheral lesions when normal tissue constraints
      are respected.

PMID- 24661666
TI  - Assessing interpersonal and communication skills in radiation oncology residents:
      a pilot standardized patient program.
AB  - PURPOSE: There is a lack of data for the structured development and evaluation of
      communication skills in radiation oncology residency training programs. Effective
      communication skills are increasingly emphasized by the Accreditation Council for
      Graduate Medical Education and are critical for a successful clinical practice.
      We present the design of a novel, pilot standardized patient (SP) program and the
      evaluation of communication skills among radiation oncology residents. METHODS
      AND MATERIALS: Two case scenarios were developed to challenge residents in the
      delivery of "bad news" to patients: one scenario regarding treatment failure and
      the other regarding change in treatment plan. Eleven radiation oncology residents
      paired with 6 faculty participated in this pilot program. Each encounter was
      scored by the SPs, observing faculty, and residents themselves based on the
      Kalamazoo guidelines. RESULTS: Overall resident performance ratings were "good"
      to "excellent," with faculty assigning statistically significant higher scores
      and residents assigning lower scores. We found inconsistent inter rater agreement
      among faculty, residents, and SPs. SP feedback was also valuable in identifying
      areas of improvement, including more collaborative decision making and less use
      of medical jargon. CONCLUSIONS: The program was well received by residents and
      faculty and regarded as a valuable educational experience that could be used as
      an annual feedback tool. Poor inter rater agreement suggests a need for residents
      and faculty physicians to better calibrate their evaluations to true patient
      perceptions. High scores from faculty members substantiate the concern that
      resident evaluations are generally positive and nondiscriminating. Faculty should
      be encouraged to provide honest and critical feedback to hone residents'
      interpersonal skills.

PMID- 24661667
TI  - Temporal lobe reactions after carbon ion radiation therapy: comparison of
      relative biological effectiveness-weighted tolerance doses predicted by local
      effect models I and IV.
AB  - PURPOSE: To compare the relative biological effectiveness (RBE)-weighted
      tolerance doses for temporal lobe reactions after carbon ion radiation therapy
      using 2 different versions of the local effect model (LEM I vs LEM IV) for the
      same patient collective under identical conditions. METHODS AND MATERIALS: In a
      previous study, 59 patients were investigated, of whom 10 experienced temporal
      lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base
      chordoma and chondrosarcoma at Helmholtzzentrum fur Schwerionenforschung (GSI) in
      Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast
      enhancements on T1-weighted MRI images within a median follow-up time of 2.5
      years. Although the derived RBE-weighted temporal lobe doses were based on the
      clinically applied LEM I, we have now recalculated the RBE-weighted dose
      distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm3
      (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding
      the volume of 1 cm3 with the highest dose) as an independent dosimetric variable.
      The resulting RBE-weighted tolerance doses were compared with those of the
      previous study to assess the clinical impact of LEM IV relative to LEM I.
      RESULTS: The dose-response curve of LEM IV is shifted toward higher values
      compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication
      probability (TD5) increases from 68.8 +/- 3.3 to 78.3 +/- 4.3 Gy (RBE) for LEM IV
      as compared to LEM I. CONCLUSIONS: LEM IV predicts a clinically significant
      increase of the RBE-weighted tolerance doses for the temporal lobe as compared to
      the currently applied LEM I. The limited available photon data do not allow a
      final conclusion as to whether RBE predictions of LEM I or LEM IV better fit
      better clinical experience in photon therapy. The decision about a future
      clinical application of LEM IV therefore requires additional analysis of temporal
      lobe reactions in a comparable photon-treated collective using the same
      dosimetric variable as in the present study.

PMID- 24661668
TI  - Intrafraction prostate translations and rotations during hypofractionated robotic
      radiation surgery: dosimetric impact of correction strategies and margins.
AB  - PURPOSE: To investigate the dosimetric impact of intrafraction prostate motion
      and the effect of robot correction strategies for hypofractionated CyberKnife
      treatments with a simultaneously integrated boost. METHODS AND MATERIALS: A total
      of 548 real-time prostate motion tracks from 17 patients were available for
      dosimetric simulations of CyberKnife treatments, in which various correction
      strategies were included. Fixed time intervals between imaging/correction (15,
      60, 180, and 360 seconds) were simulated, as well as adaptive timing (ie, the
      time interval reduced from 60 to 15 seconds in case prostate motion exceeded 3 mm
      or 2 degrees  in consecutive images). The simulated extent of robot corrections
      was also varied: no corrections, translational corrections only, and
      translational corrections combined with rotational corrections up to 5 degrees ,
      10 degrees , and perfect rotational correction. The correction strategies were
      evaluated for treatment plans with a 0-mm or 3-mm margin around the clinical
      target volume (CTV). We recorded CTV coverage (V100%) and dose-volume parameters
      of the peripheral zone (boost), rectum, bladder, and urethra. RESULTS: Planned
      dose parameters were increasingly preserved with larger extents of robot
      corrections. A time interval between corrections of 60 to 180 seconds provided
      optimal preservation of CTV coverage. To achieve 98% CTV coverage in 98% of the
      treatments, translational and rotational corrections up to 10 degrees  were
      required for the 0-mm margin plans, whereas translational and rotational
      corrections up to 5 degrees  were required for the 3-mm margin plans. Rectum and
      bladder were spared considerably better in the 0-mm margin plans. Adaptive timing
      did not improve delivered dose. CONCLUSIONS: Intrafraction prostate motion
      substantially affected the delivered dose but was compensated for effectively by
      robot corrections using a time interval of 60 to 180 seconds. A 0-mm margin
      required larger extents of additional rotational corrections than a 3-mm margin
      but resulted in lower doses to rectum and bladder.

PMID- 24661669
TI  - Quality Assurance with Plan Veto: reincarnation of a record and verify system and
      its potential value.
AB  - PURPOSE: To quantify the potential impact of the Integrating the Healthcare
      Enterprise-Radiation Oncology Quality Assurance with Plan Veto (QAPV) on patient
      safety of external beam radiation therapy (RT) operations. METHODS AND MATERIALS:
      An institutional database of events (errors and near-misses) was used to evaluate
      the ability of QAPV to prevent clinically observed events. We analyzed reported
      events that were related to Digital Imaging and Communications in Medicine RT
      plan parameter inconsistencies between the intended treatment (on the treatment
      planning system) and the delivered treatment (on the treatment machine). Critical
      Digital Imaging and Communications in Medicine RT plan parameters were
      identified. Each event was scored for importance using the Failure Mode and
      Effects Analysis methodology. Potential error occurrence (frequency) was derived
      according to the collected event data, along with the potential event severity,
      and the probability of detection with and without the theoretical implementation
      of the QAPV plan comparison check. Failure Mode and Effects Analysis Risk
      Priority Numbers (RPNs) with and without QAPV were compared to quantify the
      potential benefit of clinical implementation of QAPV. RESULTS: The implementation
      of QAPV could reduce the RPN values for 15 of 22 (71%) of evaluated parameters,
      with an overall average reduction in RPN of 68 (range, 0-216). For the 6 high
      risk parameters (>200), the average reduction in RPN value was 163 (range, 108
      216). The RPN value reduction for the intermediate-risk (200 > RPN > 100)
      parameters was (0-140). With QAPV, the largest RPN value for "Beam Meterset" was
      reduced from 324 to 108. The maximum reduction in RPN value was for Beam Meterset
      (216, 66.7%), whereas the maximum percentage reduction was for Cumulative
      Meterset Weight (80, 88.9%). CONCLUSION: This analysis quantifies the value of
      the Integrating the Healthcare Enterprise-Radiation Oncology QAPV implementation
      in clinical workflow. We demonstrate that although QAPV does not provide a
      comprehensive solution for error prevention in RT, it can have a significant
      impact on a subset of the most severe clinically observed events.

PMID- 24661671
TI  - Tumor radiation therapy creates therapeutic vaccine responses to the colorectal
      cancer antigen GUCY2C.
AB  - PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in
      cancer patients, not only through direct toxicity to cancer cells and supporting
      tumor stroma cells, but also through activation of immunologic effectors. More
      recently, RT has potentiated the local and systemic effects of cancer
      immunotherapy (IT). However, combination regimens that maximize immunologic and
      clinical efficacy remain undefined. METHODS AND MATERIALS: We evaluated the
      impact of local RT on adenoviral-mediated vaccination against the colorectal
      cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using
      mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by
      ELISpot, and clinical responses were assessed by tumor size and incidence.
      RESULTS: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT
      transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine.
      GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was
      maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors
      were irradiated before, compared with after, Ad5-GUCY2C vaccination. The
      immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by
      unfractionated (8 Gy * 1), or biologically equivalent doses of fractionated (3.5
      Gy * 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on
      expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor
      volumes were inversely related to the magnitude of GUCY2C-specific T cell
      responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long
      lasting antigen-dependent protection, resisting tumors formed by GUCY2C
      expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells.
      CONCLUSIONS: Optimal sequencing of RT and IT amplifies antigen-specific local and
      systemic immune responses, revealing novel acute and long-term therapeutic
      antitumor protection. These observations underscore the importance of modality
      sequence optimization before the initiation of clinical trials of RT and IT to
      maximize immune and antitumor responses.

PMID- 24661670
TI  - Assessing the dosimetric impact of real-time prostate motion during volumetric
      modulated arc therapy.
AB  - PURPOSE: To develop a method for dose reconstruction by incorporating the
      interplay effect between aperture modulation and target motion, and to assess the
      dosimetric impact of real-time prostate motion during volumetric modulated arc
      therapy (VMAT). METHODS AND MATERIALS: Clinical VMAT plans were delivered with
      the TrueBeam linac for 8 patients with prostate cancer. The real-time target
      motion during dose delivery was determined based on the 2-dimensional fiducial
      localization using an onboard electronic portal imaging device. The target shift
      in each image was correlated with the control point with the same gantry angle in
      the VMAT plan. An in-house-developed Monte Carlo simulation tool was used to
      calculate the 3-dimensional dose distribution for each control point
      individually, taking into account the corresponding real-time target motion
      (assuming a nondeformable target with no rotation). The delivered target dose was
      then estimated by accumulating the dose from all control points in the plan. On
      the basis of this information, dose-volume histograms and 3-dimensional dose
      distributions were calculated to assess their degradation from the planned dose
      caused by target motion. Thirty-two prostate motion trajectories were analyzed.
      RESULTS: The minimum dose to 0.03 cm(3) of the gross tumor volume (D0.03cc) was
      only slightly degraded after taking motion into account, with a minimum value of
      94.1% of the planned dose among all patients and fractions. However, the gross
      tumor volume receiving prescription dose (V100%) could be largely affected by
      motion, dropping below 60% in 1 trajectory. We did not observe a correlation
      between motion magnitude and dose degradation. CONCLUSIONS: Prostate motion
      degrades the delivered dose to the target in an unpredictable way, although its
      effect is reduced over multiple fractions, and for most patients the degradation
      is small. Patients with greater prostate motion or those treated with
      stereotactic body radiation therapy would benefit from real-time prostate
      tracking to reduce the margin.

PMID- 24661672
TI  - SPARCL1 expression increases with preoperative radiation therapy and predicts
      better survival in rectal cancer patients.
AB  - PURPOSE: The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is
      expressed in various normal tissues and many types of cancers. The function of
      SPARCL1 and its relationship to a patient's prognosis have been studied, whereas
      its relationship to radiation therapy (RT) is not known. Our aim was to
      investigate the expression of SPARCL1 in rectal cancer patients who participated
      in a clinical trial of preoperative RT. METHODS AND MATERIALS: The study included
      136 rectal cancer patients who were randomized to undergo preoperative RT and
      surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in
      normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35)
      were determined by immunohistochemistry. RESULTS: Tumors with RT had stronger
      SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong
      SPARCL1 expression was related to better survival than weak expression in
      patients with stage III tumors, independent of sex, age, differentiation, and
      margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No
      such relationship was found in the non-RT group (P=.224). Further analysis of
      interactions among SPARCL1 expression, RT, and survival showed statistical
      significance (P=.024). In patients with metastases who received RT, strong
      SPARCL1 expression was related to better survival compared to weak expression
      (P=.041) but not in the non-RT group (P=.569). CONCLUSIONS: SPARCL1 expression
      increases with RT and is related to better prognosis in rectal cancer patients
      with RT but not in patients without RT. This result may help us to select the
      patients best suited for preoperative RT.

PMID- 24661673
TI  - Development of TRAIL resistance by radiation-induced hypermethylation of DR4 CpG
      island in recurrent laryngeal squamous cell carcinoma.
AB  - PURPOSE: There are limited therapeutic options for patients with recurrent head
      and neck cancer after radiation therapy failure. To assess the use of tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) as a salvage
      chemotherapeutic agent for recurrent cancer after radiation failure, we
      investigated the effect of clinically relevant cumulative irradiation on TRAIL
      induced apoptosis. METHODS AND MATERIALS: Using a previously established HN3 cell
      line from a laryngeal carcinoma patient, we generated a chronically irradiated
      HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated
      with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting
      and flow cytometry were used to determine the underlying mechanism of TRAIL
      resistance. DR4 expression was semiquantitatively scored in a tissue microarray
      with 107 laryngeal cancer specimens. Methylation-specific polymerase chain
      reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated
      from each cell line. RESULTS: HN3R cells were more resistant than HN3 cells to
      TRAIL-induced apoptosis because of significantly reduced levels of the DR4
      receptor. The DR4 staining score in 37 salvage surgical specimens after radiation
      failure was lower in 70 surgical specimens without radiation treatment (3.03 +/-
      2.75 vs 5.46 +/- 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG
      island that was partially demethylated by the DNA demethylating agent 5-aza-2'
      deoxycytidine. CONCLUSION: Epigenetic silencing of the TRAIL receptor by
      hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL
      resistance in recurrent laryngeal carcinoma treated with radiation.

PMID- 24661674
TI  - We need better figures! In regard to Lee.

PMID- 24661675
TI  - Parotid glands dose-effect relationships based on their actually delivered doses:
      implications for adaptive replanning in radiation therapy of head-and-neck
      cancer: in regard to Hunter et al.

PMID- 24661676
TI  - In reply to Bauman.

PMID- 24661677
TI  - In reply to Ren et al.

PMID- 24661678
TI  - Edmond-Philippe Malaise (1930-2013): a lifetime of perseverance leads to the
      cellular definition of intrinsic radiosensitivity.

PMID- 24661679
TI  - An overlapping set of genes is regulated by both NFIB and the glucocorticoid
      receptor during lung maturation.
AB  - BACKGROUND: Lung maturation is a late fetal developmental event in both mice and
      humans. Because of this, lung immaturity is a serious problem in premature
      infants. Disruption of genes for either the glucocorticoid receptor (Nr3c1) or
      the NFIB transcription factors results in perinatal lethality due to lung
      immaturity. In both knockouts, the phenotype includes excess cell proliferation,
      failure of saccularization and reduced expression of markers of epithelial
      differentiation. This similarity suggests that the two genes may co-regulate a
      specific set of genes essential for lung maturation. RESULTS: We analyzed the
      roles of these two transcription factors in regulating transcription using ChIP
      seq data for NFIB, and RNA expression data and motif analysis for both. Our new
      ChIP-seq data for NFIB in lung at E16.5 shows that NFIB binds to a NFI motif.
      This motif is over-represented in the promoters of genes that are under-expressed
      in Nfib-KO mice at E18.5, suggesting an activator role for NFIB. Using available
      microarray data from Nr3c1-KO mice, we further identified 52 genes that are under
      expressed in both Nfib and Nr3c1 knockouts, an overlap which is 13.1 times larger
      than what would be expected by chance. Finally, we looked for enrichment of 738
      recently published transcription factor motifs in the promoters of these putative
      target genes and found that the NFIB and glucocorticoid receptor motifs were
      among the most enriched, suggesting that a subset of these genes may be directly
      activated by Nfib and Nr3c1. CONCLUSIONS: Our data provide the first evidence for
      Nfib and Nr3c1 co-regulating genes related to lung maturation. They also
      establish that the in vivo DNA-binding specificity of NFIB is the same as
      previously seen in vitro, and highly similar to that of the other NFI-family
      members NFIA, NFIC and NFIX.

PMID- 24661680
TI  - BMP4 and FGF3 haplotypes increase the risk of tendinopathy in volleyball
      athletes.
AB  - OBJECTIVES: To investigate whether genetic variants can be correlated with
      tendinopathy in elite male volleyball athletes. DESIGN: Case-control study.
      METHODS: Fifteen single nucleotide polymorphisms within BMP4, FGF3, FGF10, FGFR1
      genes were investigated in 138 elite volleyball athletes, aged between 18 and 35
      years, who undergo 4-5h of training per day: 52 with tendinopathy and 86 with no
      history of pain suggestive of tendinopathy in patellar, Achilles, shoulder, and
      hip abductors tendons. The clinical diagnostic criterion was progressive pain
      during training, confirmed by magnetic resonance image. Genomic DNA was obtained
      from saliva samples. Genetic markers were genotyped using TaqMan real-time PCR.
      Chi-square test compared genotypes and haplotype differences between groups.
      Multivariate logistic regression analyzed the significance of covariates and
      incidence of tendinopathy. RESULTS: Statistical analysis revealed participant age
      (p=0.005) and years of practice (p=0.004) were risk factors for tendinopathy. A
      significant association between BMP4 rs2761884 (p=0.03) and tendinopathy was
      observed. Athletes with a polymorphic genotype have 2.4 times more susceptibility
      to tendinopathy (OR=2.39; 95%CI=1.10-5.19). Also, association between disease and
      haplotype TTGGA in BMP4 (p=0.01) was observed. The FGF3 TGGTA haplotype showed a
      tendency of association with tendinopathy (p=0.05), and so did FGF10 rs900379.
      FGFR1 showed no association with disease. CONCLUSIONS: These findings indicate
      that haplotypes in BMP4 and FGF3 genes may contribute to the tendon disease
      process in elite volleyball athletes.

PMID- 24661681
TI  - Prediction of gait recovery in spinal cord injured individuals trained with
      robotic gait orthosis.
AB  - BACKGROUND: Motor impairment is a major consequence of spinal cord injury (SCI).
      Earlier studies have shown that robotic gait orthosis (e.g., Lokomat) can improve
      an SCI individual's walking capacity. However, little is known about the
      differential responses among different individuals with SCI. The present
      longitudinal study sought to characterize the distinct recovery patterns of gait
      impairment for SCI subjects receiving Lokomat training, and to identify
      significant predictors for these patterns. METHODS: Forty SCI subjects with
      spastic hypertonia at their ankles were randomly allocated to either control or
      intervention groups. Subjects in the intervention group participated in twelve 1
      hour Lokomat trainings over one month, while control subjects received no
      interventions. Walking capacity was evaluated in terms of walking speed,
      functional mobility, and endurance four times, i.e. baseline, 1, 2, and 4 weeks
      after training, using the 10-Meter-Walking, Timed-Up-and-Go, and 6-Minute-Walking
      tests. Growth Mixture Modeling, an analytical framework for stratifying subjects
      based on longitudinal changes, was used to classify subjects, based on their gait
      impairment recovery patterns, and to identify the effects of Lokomat training on
      these improvements. RESULTS: Two recovery classes (low and high walking capacity)
      were identified for each clinical evaluation from both the control and
      intervention groups. Subjects with initial high walking capacity (i.e. shorter
      Timed-Up-and-Go time, higher 10-Meter-Walking speed and longer 6-Minute-Walking
      distance) displayed significant improvements in speed and functional mobility
      (0.033 m/s/week and-0.41 s/week respectively); however no significant change in
      endurance was observed. Subjects with low walking capacity exhibited no
      significant improvement. The membership in these two classes-and thus prediction
      of the subject's gait improvement trajectory over time-could be determined by the
      subject's maximum voluntary torque at the ankle under both plantar-and dorsi
      flexion contractions determined prior to any training. CONCLUSION: Our findings
      demonstrate that subjects responded to Lokomat training non-uniformly, and should
      potentially be grouped based on their likely recovery patterns using objective
      criteria. Further, we found that the subject's ankle torque can predict whether
      he/she would benefit most from Lokomat training prior to the therapy. These
      findings are clinically significant as they can help individualize therapeutic
      programs that maximize patient recovery while minimizing unnecessary efforts and
      costs.

PMID- 24661682
TI  - Concomitant tricuspid valve surgery during implantation of continuous-flow left
      ventricular assist devices: a Society of Thoracic Surgeons database analysis.
AB  - BACKGROUND: Performing concomitant tricuspid valve procedures (TVPs) in left
      ventricular assist device (LVAD) patients with significant pre-operative
      tricuspid regurgitation (TR) is controversial, and no studies have been large
      enough to definitively guide therapy. METHODS: Between January 2006 and September
      2012, 2,196 patients with moderate to severe pre-operative TR from 115
      institutions underwent implantation of a continuous-flow left ventricular assist
      device (LVAD) as reported by The Society of Thoracic Surgeons National Database.
      Of these, 588 (27%) underwent a concomitant TVP. Inverse probability weighting
      based on propensity score was used to adjust for differences between the LVAD
      alone and LVAD+TVP groups, and outcomes were compared. RESULTS: Most patients in
      the LVAD+TVP group underwent an annuloplasty alone (81.1%). Concomitant TVP did
      not affect risk of post-operative right VAD insertion (risk ratio [RR], 0.81; 95%
      confidence interval [CI], 0.49-1.36; p = 0.4310) or death (RR, 0.95; 95% CI, 0.68
      1.33; p = 0.7658). However, TVP was associated with an increased risk for post
      operative renal failure (RR, 1.53; 95% CI, 1.13-2.08; p = 0.0061), dialysis (RR,
      1.49; 95% CI, 1.03-2.15; p = 0.0339), reoperation (RR, 1.24; 95% CI, 1.07-1.45; p
      = 0.0056), greater total transfusion requirement (RR, 1.03; 95% CI, 1.01-1.05; p
      = 0.0013), and hospital length of stay > 21 days (RR, 1.29; 95% CI, 1.16-1.43; p
      < 0.0001). Time on the ventilator and intensive care unit length of stay were
      also significantly prolonged for the LVAD+TVP group. CONCLUSIONS: Performing a
      concomitant TVP for continuous-flow LVAD patients with moderate to severe TR did
      not reduce early death or right VAD requirement and was associated with worse
      early post-operative outcomes. These data caution against routine concomitant TVP
      based solely on degree of pre-operative TR and suggest that additional selection
      criteria are needed to identify those patients in whom concomitant TVP may
      prevent post-operative right ventricular failure.

PMID- 24661683
TI  - Practical value of identifying antibodies to cryptic HLA epitopes in cardiac
      transplantation.
AB  - BACKGROUND: Identification of antibodies to human leukocyte antigens (HLA) by
      single antigen bead arrays has led to the common practice of virtual
      crossmatching. However, inappropriate assignment of anti-HLA specificities can
      lead to false-positive virtual crossmatching, resulting in the decline of
      potentially crossmatch-negative organ offers. In this study we describe
      identification of antibodies to cryptic HLA present on denatured forms of HLA on
      single antigen bead array and provide a reassessment of calculated panel-reactive
      antibody (CPRA) based on elimination of false-positive reactions due to
      antibodies to cryptic HLA epitopes. METHODS: Sera from 96 patients with positive
      HLA antibodies detected on a standard single antigen bead platform were tested
      under denaturing conditions and with a new single antigen bead product (iBeads;
      One Lambda, Inc., Canoga Park, CA) to identify antibodies to cryptic HLA vs.
      native HLA. Flow cytometry crossmatching and complement-fixation assays were
      performed to assess clinical relevance. RESULTS: Antibodies to cryptic HLA were
      present in approximately 21% of patients on our waiting list for cardiac
      transplantation. These antibody responses were not associated with factors
      commonly thought to be associated with antibody responses to HLA such as age,
      gender, transfusions or presence of circulatory support. CONCLUSIONS: Antibodies
      to cryptic HLA can be reliably identified by iBeads technology, and usually do
      not fix complement nor produce positive flow cytometry crossmatches.
      Identification and removal of antibodies to cryptic HLA from the panel of
      unacceptable antigens may have dramatic and meaningful effects on CPRA and
      virtual crossmatch strategies.

PMID- 24661684
TI  - Single-center experience with extracorporeal photopheresis in pediatric heart
      transplantation.
AB  - BACKGROUND: The pediatric heart transplant literature contains little information
      regarding extracorporeal photopheresis (ECP), despite International Society for
      Heart and Lung Transplantation guidelines recommending it for
      recurrent/recalcitrant rejection. We report our experience with ECP in pediatric
      heart transplantation. METHODS: Data were obtained on heart transplant patients
      who were aged <= 18 years at the time of transplantation and received ECP between
      1990 and 2012 at our institution. RESULTS: Twenty heart transplant patients
      underwent 22 courses of ECP. Median ages were 12.7 years (range, 0.3-18.5 years)
      at transplant and 15.3 years (range, 7.3-31 years) at initial ECP. Median time
      from transplant to ECP was 1.4 years (range, 0.1-12.6 years). The median ECP
      duration was 5.8 months (range, 1.9-16.1 months). Indications for ECP included
      rejection with hemodynamic compromise (HC) in 4 patients, rejection without HC in
      12, and prophylaxis in 2. Eleven patients died at a median time of 3.1 years
      after the start of ECP. Survival after ECP was 84% at 1 year and 53% at 3 years.
      Eleven patients were considered non-compliant and had a trend toward lower
      survival of 75% at 1 year and 18% at 3 years (p = 0.06 compared with compliant
      patients). One patient developed Pneumocystis carinii pneumonia during ECP and
      post-transplant lymphoproliferative disease 21 months after finishing ECP. No
      other adverse effects or infectious complications associated with ECP were noted.
      CONCLUSIONS: This case series represents the largest reported experience with ECP
      in pediatric heart transplantation. ECP can be safely applied in this patient
      group. Despite EPC, non-compliant patients showed a trend toward lower survival
      than compliant patients.

PMID- 24661685
TI  - Inappropriate initial antibiotic treatment for complicated skin and soft tissue
      infections in hospitalized patients: incidence and associated factors.
AB  - We analyzed 525 hospitalized adults treated with intravenous antibiotic(s) for
      complicated skin and soft tissue infections (cSSTIs) to assess incidence of, and
      risk factors associated with, inappropriate initial antibiotic treatment (IIAT).
      IIAT was given to 22.5% of enrolled patients. The rate of IIAT did not vary by
      type of facility (academic versus community) but was significantly higher in
      rural than urban hospitals (38.9% versus 21.3%, P = 0.02). Pathogens were
      exclusively gram-positive in 68% of patients, exclusively gram-negative in 13%,
      and mixed in 19%. Staphylococcus aureus was the most frequently isolated pathogen
      (in 65%), 54% of which were methicillin-resistant. Significant independent risk
      factors for IIAT were: admission to a rural hospital (odds ratio = 2.34; 95%
      confidence interval: 1.06-5.19), dialysis treatment (3.86; 1.15-12.93), cancer
      other than non-melanoma skin cancer (5.23; 1.78-15.36), and infection with gram
      negative (3.43; 1.79-6.60) or mixed (4.52; 2.62-7.78) pathogens. IIAT for cSSTIs
      was relatively frequent in these hospitalized patients, especially those with
      selected risk factors. 

PMID- 24661686
TI  - Performance of a rapid multi-analyte 2-photon excitation assay in children with
      acute respiratory infection.
AB  - The purpose of this study is to evaluate the diagnostic performance of the novel
      2-photon excitation-based mariPOC(c) Assay (ArcDia Laboratories, Turku, Finland)
      for antigen detection of respiratory viruses versus real-time polymerase chain
      reaction (PCR). The mariPOC Assay and 2 multiplex real-time PCR techniques were
      performed on nasopharyngeal samples from pediatric patients with suspicion of
      acute respiratory infection admitted to a children's hospital in Spain during
      October 2011 to January 2013. A total of 233 samples were studied. Sensitivities
      and specificities (95% confidence interval) of the mariPOC Assay were for
      respiratory syncytial virus (RSV), 78.4% (69.7-85.6) and 99.2% (96.3-100.0);
      influenza virus (IFV) A, 66.7% (26.2-94.0) and 99.6% (97.9-100.0); IFV-B, 63.6%
      (33.6-87.2) and 100.0% (98.7-100.0); human metapneumovirus (hMPV), 60.0% (34.5
      81.9) and 100.0% (98.6-100.0); adenovirus (ADV), 12.5% (0.6-48.0) and 100.0%
      (98.7-100.0), respectively. The mariPOC Assay is a highly specific method for
      simultaneous detection of 8 respiratory viruses but has sensitivities that range
      from moderately high for RSV to moderate for IFV and hMPV and low for ADV. 

PMID- 24661687
TI  - Dural plasmacytoma: an unusual presentation.

PMID- 24661688
TI  - Predictors of physical restraint use in Canadian intensive care units.
AB  - INTRODUCTION: Physical restraint (PR) use in the intensive care unit (ICU) has
      been associated with higher rates of self-extubation and prolonged ICU length of
      stay. Our objectives were to describe patterns and predictors of PR use. METHODS:
      We conducted a secondary analysis of a prospective observational study of
      analgosedation, antipsychotic, neuromuscular blocker, and PR practices in 51
      Canadian ICUs. Data were collected prospectively for all mechanically ventilated
      adults admitted during a two-week period. We tested for patient, treatment, and
      hospital characteristics that were associated with PR use and number of days of
      use, using logistic and Poisson regression respectively. RESULTS: PR was used on
      374 out of 711 (53%) patients, for a mean number of 4.1 (standard deviation (SD)
      4.0) days. Treatment characteristics associated with PR were higher daily
      benzodiazepine dose (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.00 to
      1.11), higher daily opioid dose (OR 1.04, 95% CI 1.01 to 1.06), antipsychotic
      drugs (OR 3.09, 95% CI 1.74 to 5.48), agitation (Sedation-Agitation Scale (SAS)
      >4) (OR 3.73, 95% CI 1.50 to 9.29), and sedation administration method
      (continuous and bolus versus bolus only) (OR 3.09, 95% CI 1.74 to 5.48). Hospital
      characteristics associated with PR indicated patients were less likely to be
      restrained in ICUs from university-affiliated hospitals (OR 0.32, 95% CI 0.17 to
      0.61). Mainly treatment characteristics were associated with more days of PR,
      including: higher daily benzodiazepine dose (incidence rate ratio (IRR) 1.07, 95%
      CI 1.01 to 1.13), daily sedation interruption (IRR 3.44, 95% CI 1.48 to 8.10),
      antipsychotic drugs (IRR 15.67, 95% CI 6.62 to 37.12), SAS <3 (IRR 2.62, 95% CI
      1.08 to 6.35), and any adverse event including accidental device removal (IRR
      8.27, 95% CI 2.07 to 33.08). Patient characteristics (age, gender, Acute
      Physiology and Chronic Health Evaluation II score, admission category, prior
      substance abuse, prior psychotropic medication, pre-existing psychiatric
      condition or dementia) were not associated with PR use or number of days used.
      CONCLUSIONS: PR was used in half of the patients in these 51 ICUs. Treatment
      characteristics predominantly predicted PR use, as opposed to patient or
      hospital/ICU characteristics. Use of sedative, analgesic, and antipsychotic
      drugs, agitation, heavy sedation, and occurrence of an adverse event predicted PR
      use or number of days used.

PMID- 24661689
TI  - Treatment of infectious disease: beyond antibiotics.
AB  - Several antibiotics have been discovered following the discovery of penicillin.
      These antibiotics had been helpful in treatment of infectious diseases considered
      dread for centuries. The advent of multiple drug resistance in microbes has posed
      new challenge to researchers. The scientists are now evaluating alternatives for
      combating infectious diseases. This review focuses on major alternatives to
      antibiotics on which preliminary work had been carried out. These promising anti
      microbial include: phages, bacteriocins, killing factors, antibacterial
      activities of non-antibiotic drugs and quorum quenching. 

PMID- 24661690
TI  - Hostile-Helpless state of mind as further evidence of adult disorganized states
      of mind in neglecting families.
AB  - This study aimed to assess disorganized states of mind in a sample of neglecting
      and at-risk of neglecting mothers using the recently developed Hostile-Helpless
      (HH) coding system (Lyons-Ruth et al., 2006) for the Adult Attachment Interview
      (Main & Goldwyn, 1998). The relation between HH states of mind and mothers'
      childhood traumas was also examined. Participants were 70 neglecting mothers and
      at-risk of neglecting mothers. Childhood traumas were assessed using the
      Childhood Trauma Questionnaire. HH states of mind were coded from Adult
      Attachment Interview transcripts by two reliable coders. Results revealed a high
      prevalence of disorganized states of mind in this sample. Forty-five mothers were
      classified HH, representing 64% of the entire sample. Most mothers reported at
      least one form of childhood trauma, with a mean of 2.9 different forms of trauma.
      Mothers classified HH reported having been emotionally abused, sexually abused
      and physically neglected more frequently than non-HH mothers. There was no
      difference between neglecting and at-risk of neglect mothers on HH states of mind
      and childhood experiences of trauma. These findings are in line with theorization
      on maltreating mothers' psychological background and they provide further
      empirical support to the validation of the HH classification system with at-risk
      populations. 

PMID- 24661691
TI  - Child and adolescent abuse and neglect in the city of Curitiba, Brazil.
AB  - Identify and analyze cases of child and adolescent abuse and neglect in Curitiba,
      Brazil. This is an exploratory descriptive study that takes a quantitative
      approach. Secondary data from the reporting registry of the Network for the
      Protection of Children and Adolescents at Risk for Violence in Curitiba, Brazil,
      dating from 2004 to 2009, were analyzed. Variables included the victims'
      sociodemographic profile, place of notification, type, nature and severity of
      abuse, information about the author of the aggression or abuse, and physical
      lesions. The frequency distribution and associations between the variables were
      analyzed using the Chi-square test at a 5% significance level. The analysis of
      19,316 records showed that domestic violence, abuse and neglect directed against
      children and adolescents were the most frequently recorded situation, with 17,082
      cases (88.4%) distributed in the following manner: neglect, with 9742 reports
      (57.0%); physical violence, with 1341 reports (7.9%); sexual violence, with 796
      reports (4.7%); psychological violence, with 574 reports (3.4%); and abandonment,
      with 190 reports (1.1%). Of the total, 43.9% were considered severe cases. The
      most affected age group was between 5 and 14 years of age, with balance between
      genders. In the majority of cases, the mother was registered as the author of the
      abuse or neglect. Physical sequelae (20.2%) mostly affected the head and upper
      and lower limbs, with consequent lesions manifesting as bruises, cuts, and
      fractures. An increase in the visibility of domestic violence and children and
      adolescents abuse and neglect has been observed in the city during the last few
      years, suggesting the effectiveness of the reporting strategies proposed by the
      protection network. It is important to increase social security and public
      welfare policies to prevent child and adolescent abuse and neglect, focusing on
      family support. 

PMID- 24661692
TI  - Parental harsh discipline in mainland China: prevalence, frequency, and
      coexistence.
AB  - The study examined the prevalence, frequency, and coexistence of psychological
      aggression (PA), corporal punishment (CP), and severe physical abuse (SPA) in
      mainland China. Using a sample of 2,518 father-mother dyads of 3-15-year-old
      children, the findings revealed that parental harsh discipline was prevalent in
      mainland China. The rates of harsh discipline in the current study fell in the
      middle of the ranges of rates found in other studies. Harsh discipline was most
      likely directed at boys or children aged 7 years and committed by mothers, young
      fathers, or high and low socioeconomic status (SES) parents. The prevalence of
      maternal and paternal PA and CP declined with the children's age. Maternal and
      paternal SPA first increased and then decreased with child age. The frequency of
      the three types of maternal and paternal harsh discipline fluctuated depending on
      the age of the children. In addition, approximately 50% of the mothers and
      fathers who reported using severe forms of disciplinary practices also engaged in
      less severe forms of harsh disciplinary practices against their children. SPA
      generally coexisted with CP and PA, and CP was usually accompanied by PA;
      however, PA was more likely to occur independently compared with CP and SPA.
      Moreover, maternal harsh discipline coexisted with paternal harsh discipline to
      some extent. The coexistence decreased with increasing severity of parental harsh
      discipline and differed according to child gender. These findings highlight the
      importance of studying these three types of parental harsh discipline
      simultaneously and intervening in harsh discipline by mothers and fathers within
      the same family. 

PMID- 24661693
TI  - Effects of the child-perpetrator relationship on mental health outcomes of child
      abuse: it's (not) all relative.
AB  - The present study was conducted to better understand the influence of the child
      perpetrator relationship on responses to child sexual and physical trauma for a
      relatively large, ethnically diverse sample of children and youth presenting for
      clinical evaluation and treatment at child mental health centers across the
      United States. This referred sample includes 2,133 youth with sexual or physical
      trauma as their primary treatment focus. Analyses were conducted to ascertain
      whether outcomes were dependent on the perpetrator's status as a caregiver vs.
      non-caregiver. Outcome measures included psychiatric symptom and behavior problem
      rating scales. For sexual trauma, victimization by a non-caregiver was associated
      with higher posttraumatic stress, internalizing and externalizing behavior
      problems, depression, and dissociation compared to youth victimized by a
      caregiver. For physical trauma, victimization by a non-caregiver was also
      associated with higher posttraumatic symptoms and internalizing behavior
      problems. The total number of trauma types experienced and age of physical or
      sexual trauma onset also predicted several outcomes for both groups, although in
      disparate ways. These findings are consistent with other recent studies
      demonstrating that perpetration of abuse by caregivers results in fewer symptoms
      and problems than abuse perpetrated by a non-caregiving relative. Thus,
      clinicians should not make a priori assumptions that children and adolescents who
      are traumatized by a parent/caregiver would have more severe symptoms than youth
      who are traumatized by a non-caregiver. Further exploration of the role of the
      perpetrator and other trauma characteristics associated with the perpetrator role
      is needed to advance our understanding of these findings and their implications
      for clinical practice. 

PMID- 24661694
TI  - Candida albicans spondylodiscitis following an abdominal stab wound: forensic
      considerations.
AB  - Candida albicans spondylodiscitis is a fungal infection of the spine which is
      still unusual in spite of the increasing frequency of predisposing factors. A 22
      year-old man received an abdominal stab wound during a physical assault. Initial
      medical care included surgery, prolonged use of indwelling vascular catheters
      with administration of broad-spectrum antibiotics, and hospitalization in
      intensive care. Two months after the event, the victim experienced back pain in
      the right lumbar region and septic spondylodiscitis secondary to C. albicans was
      diagnosed three weeks later. This case is noteworthy because of its clinical
      forensic context. In France, the public prosecutor orders a medico-legal
      assessment after an assault for all living victims in order to establish a causal
      relationship between the assault and its complications. In our case, the patient
      presented numerous risk factors for candidemia and the forensic specialist
      reasonably accepted that the causal relationship was certain but indirect. We
      have only found one published case of spondylodiscitis after an abdominal
      penetrating injury and the pathogenic agent was not mentioned. We have found no
      case reported in a forensic context. This unusual observation shows that it may
      be genuinely difficult to prove the causal relationship between an abdominal
      penetrating injury and an unusual infectious complication such as fungal
      spondylodiscitis. 

PMID- 24661695
TI  - Letter to the editor.

PMID- 24661696
TI  - Foreign bodies ingestion: what responsibility?
AB  - The ingestion of foreign bodies is one of the most important and difficult
      emergencies for a physician to diagnose. Accidental ingestion is more common in
      children, in patients with dental implants, in individuals with mental disability
      and in drug users. Voluntary ingestion is found in patients who are
      psychologically unstable, in prisoners or those who attempt suicide. Foreign
      bodies may be divided into food as fish bones, chicken bones, food bolus, meat,
      etc. or real foreign bodies such as orthodontic implants, needles, pins, glass,
      coins, etc. The authors present a case of management, from the medicolegal point
      of view, of a female patient age 80, who complained, for some weeks of modest
      pain in the left iliac fossa, and afterwards the endoscopy showed a toothpick
      into the wall of the sigmoid colon. Assessed of the clinical status of the
      patient presented severe cardiac comorbidities so that before processing the
      patient to a second resolutive endoscopy, it was necessary to obtain the
      hemodynamic stability. However the management of cases of accidental ingestion of
      foreign bodies is particularly difficult. Medical errors can arise from the very
      first contact with the patient resulting in delays in appropriate treatment. The
      doctor to avoid compromising its position on medical liability, must use all the
      knowledge and diligence known by the art and science of medicine. 

PMID- 24661697
TI  - Traumatic acute myocardial ischaemia involving two vessels.
AB  - Myocardial infarctions caused by coronary artery injury after blunt chest trauma
      is a fatal, but rare occurrence. In the case reported on here, a fatally injured
      69-year-old male driver sustained such trauma in a frontal car collision. The
      autopsy found a laceration of the left anterior descending artery as well as a
      subsequent subepicardial haematoma surrounding this artery and the circumflex
      artery. Using triphenyl tetrasolium chloride and hematoxillin-eosin stains, an
      acute myocardial ischaemia of the anterior left ventricle wall and the septum was
      diagnosed as the cause of death. Since coronary injuries affecting more than one
      vessel in blunt chest trauma are extremely rare, only a few papers have yet to
      refer to this type of coronary injury in addition to the case presented here. 

PMID- 24661698
TI  - Measurement of beta-tryptase in postmortem serum in cardiac deaths.
AB  - Mast cells are well known for their role in hypersensitivity reactions. However,
      there is increasing evidence that they might also participate in both developing
      and weakening atherosclerotic plaques, potentially causing plaque instability.
      Some clinical studies have therefore postulated the existence of relationships
      between blood beta-tryptase levels and acute coronary syndromes. In this study,
      we investigated postmortem serum beta-tryptase levels in a series of 90 autopsy
      cases with various degrees of coronary atherosclerosis that had undergone medico
      legal investigations. beta-tryptase concentrations in these cases were compared
      to levels observed in 6 fatal anaphylaxis cases following contrast material
      administration. Postmortem serum beta-tryptase concentrations in the anaphylactic
      deaths ranged from 146 to 979 ng/ml. In 9 out of 90 cases of cardiac deaths, beta
      tryptase levels were higher than clinical reference values of 11.4 ng/ml and
      ranged from 21 to 65 ng/ml. These results indicate that increased postmortem
      serum beta-tryptase levels can be observed, though not systematically, in cardiac
      deaths with varying degrees of coronary atherosclerosis disease, thereby
      suggesting that mast cell activation in this disease cannot be ascertained by
      postmortem serum beta-tryptase measurements.

PMID- 24661699
TI  - Forensic problems with the composition and content of herbal medicines.
AB  - A survey of herbal medicines available for internet and over-the-counter purchase
      in South Australia, Australia, was conducted looking specifically at those used
      for 'arthritis', 'cold and flu', 'gastrointestinal', 'stress' and 'premenstrual
      syndrome'. 121 products consisted of 29 in the 'arthritis' category, 33 in 'cold
      and flu', 19 in 'gastrointestinal' 30 in 'stress' and 10 in 'premenstrual
      syndrome'. Twenty two (18%) of 121 products were not registered with the
      Australian Register of Therapeutic Goods (ARTG), despite this being a legal
      requirement for their sale. Of the registered products 59 (60%) of 99 had
      differing ingredient concentrations on the website compared to their ARTG
      listing. Only three of the 15 purchased products had ingredient concentrations
      which were consistent between the website, ARTG listing and product packaging.
      These findings demonstrate that it may not be possible to determine what herbal
      substance an individual has been exposed to prior to death and in what
      concentration, based on packaging from medications seized at the scene, or from
      examination of website data and the ARTG listing. These discrepancies may
      increase the problems that exist in attempting to determine what role herbal
      medicines may play in the mechanism of death in certain forensic cases. 

PMID- 24661700
TI  - Women convicted of a sexual offence, including child pornography production: two
      case reports.
AB  - All available studies addressing the clinical and legal aspects of child
      pornography have systematically concerned male abusers. The social lens through
      which women are viewed tends to play down their responsibility in the sexual
      abuse of children. Unlike men, women rarely abuse children outside the close or
      family circle. Furthermore, they have frequently been abused themselves in their
      childhood. To our knowledge, no cases of women charged with sex-related offences,
      including child pornography, have been described in the literature. The
      psychopathological characteristics of female sexual abusers and of the two women
      in our cases tend to suggest that the deliberate downloading of child pornography
      images by women is unusual, as their deviant behaviour is not related to
      paedophile sexual arousal It is hypothesized that the act enables women
      perpetrators to satisfy the sexual urges of their spouse. Sexual abuse by women
      exists, but the nature of the abuse appears to be specific to the gender of the
      perpetrator. We present two cases of women charged with sexual offences
      concerning minors, including the production of child pornography material. 

PMID- 24661701
TI  - Significance of 'Letters to the Editor' in research.

PMID- 24661702
TI  - Hair analysis to demonstrate administration of amitriptyline, temazepam, tramadol
      and dihydrocodeine to a child in a case of kidnap and false imprisonment.
AB  - Amitriptyline, temazepam, tramadol and dihydrocodeine are prescription-only
      medications that are rarely prescribed to children. Each of these drugs has a
      sedative effect on the central nervous system; their combined use could cause an
      exacerbation of the sedative effects. Amitriptyline (a tricyclic antidepressant)
      can be prescribed to treat nocturnal enuresis; temazepam (a hypnotic) can be used
      as a premedicant in inpatient and day-case surgery; tramadol (a synthetic opioid
      analgesic) is used to treat moderate or severe pain, though it is not recommended
      for children under the age of 12 years and dihydrocodeine (opioid analgesic),
      which is available in combination with acetaminophen (Co-dydramol), is not
      recommended for children under the age of 4 years; in children over 4 years, a
      reduced dose is necessary. The North West Forensic Science Service Laboratory,
      Euxton, Lancashire, was asked by a British police force to analyze three separate
      hair samples, which had been collected from a young child following their
      discovery as a result of a large scale kidnap and false imprisonment
      investigation. After decontamination and segmentation (20 x 1-cm section), two of
      the three hair specimens were analyzed by liquid chromatography coupled with
      tandem mass spectrometry after alkaline (pH 9.5) extraction using methylene
      chloride/isopropanol/n-heptane (25:10:65, v/v/v). The entire length of each hair
      specimen tested positive for amitriptyline and nortriptyline (7-314 pg/mg
      amitriptyline; 7-318 pg/mg nortriptyline), temazepam (2-29 pg/mg), tramadol (60
      2000 pg/mg) and dihydrocodeine (10-90 pg/mg) demonstrating that the child had
      ingested these drugs on more than one occasion prior to the kidnap. In this case,
      the child's mother and the mothers' partner were found guilty of kidnap, false
      imprisonment and perverting the course of justice. There are very few studies
      citing the concentrations of these drugs in children - especially children's hair
      samples. This case demonstrates the added value of hair testing and emphasizes
      the importance of using hair samples to complement conventional analysis.

PMID- 24661703
TI  - Tramadol deaths in Northern Ireland: a review of cases from 1996 to 2012.
AB  - In the UK tramadol is a frequently prescribed opioid analgesic which is becoming
      increasingly popular as a drug of misuse. Its use varies worldwide and in the
      last decade it has been upgraded to a controlled substance in several countries,
      due to an increased number of deaths associated with its use. A review of all
      deaths associated with tramadol in Northern Ireland was performed and this
      highlighted 127 cases from 1996 to the end of 2012. A 10% increase in deaths due
      to tramadol was noted. In 2001 tramadol deaths represented 9% of all drug misuse
      deaths rising to 40% in 2011. The majority of the deaths occurred in males (62%),
      with a median age of 41 years, living in the Belfast city area (36%). Tramadol
      fatalities were found in combination with other drugs/medicines (49%), alcohol
      (36%) or alone (23%). Most of those who died did not reach hospital, with only 2%
      presenting with multi-organ or acute liver failure. In just over half of the
      deaths tramadol had not been prescribed by a medical practitioner (53%).
      Depression, addiction and seizures were recognised risk factors. An increase in
      awareness of tramadol toxicity is needed amongst the public and doctors. 

PMID- 24661704
TI  - Determination of cocaine and its major metabolite benzoylecgonine in several
      matrices obtained from deceased individuals with presumed drug consumption prior
      to death.
AB  - In the field of forensic toxicology, femoral blood is the most useful sample for
      the determination and quantification of drugs; however, cases in which blood is
      unavailable are common. In such cases, validated methodologies for drug
      determination in alternative matrices can be decisive in the investigation of a
      case. In particular, when femoral blood is unavailable for analysis for the
      presence of systemic exposure to cocaine and its principal metabolite,
      benzoylecgonine, validated methodologies from matrices other than blood that can
      be obtained in the autopsy room would be useful to the forensic toxicologist in
      the evaluation of a specific forensic case. To address this issue, we implemented
      and compared in our study the systematic evaluation of extraction,
      chromatographic separation, and quantification of cocaine and benzoylecgonine in
      different biological matrices (right and left cardiac blood, femoral arterial and
      venous blood, urine, vitreous humor, cerebrospinal fluid, brain accumbens
      nucleus, brain ventral tegmental area, and liver). The studied matrices were
      those most likely to be obtained from different autopsy rooms at the time of
      forensic testing in deceased individuals who are presumed of antemortem drug
      consumption. Solid phase extraction of analytes from the different matrices was
      performed using C-8/SCX mixed-phase columns, and gas chromatographic mass
      spectrometry separation was performed using detection in single-ion monitoring
      mode. The methodological validation was performed for all the studied matrices,
      and the results showed similar sensitivity and recoveries without statistical
      differences between the studied matrices. The methods were applied to evaluate a
      thanatological case using all the study matrices, showing unequal postmortem
      distribution of cocaine and benzoylecgonine throughout the different matrices
      tested. The present work opens the option of applying appropriate methodologies
      in the analysis of matrices, other than the usual blood, to obtain reliable
      results that may help clarify a forensic case. In addition, we present findings
      from different studies. This work affirms not only the potentiality of obtaining
      reliable data but also reaffirms the challenge of applying these data and taking
      into account the complexity of interpreting results in matrices other than blood.

PMID- 24661705
TI  - Cardiac histopathological and immunohistochemical changes due to electric injury
      in rats.
AB  - It has been a puzzling forensic task to determine the cause of death as a result
      of electric shock in the absence of recognizable skin marks or definite
      postmortem morphological findings. In forensic pathology, while classical
      macroscopic and microscopic morphology remain core procedures to investigate
      deaths, a variety of subsidiary measures has been developed and incorporated to
      detail that pathology. C-fos, one of a small group of genes called primary
      response genes and its protein product, fos, are crucial elements of complex
      signaling mechanisms believed to be responsible for cell response to stimulation.
      It has been found that c-fos plays a significant role in myocardial lesions, and
      has close relation to injury repair of the molecule. The aim of this study was to
      detect the histopathological findings in the myocardium after fatal and non-fatal
      electrical injury in rats and to investigate the potential role of c-fos
      expression using immunohistochemistry to distinguish antemortem from postmortem
      electrocution. Forty adult female rats were implemented and randomly divided into
      four groups (A, B, C and D). Group (A) rats were subjected to instantaneous
      antemortem electricity and their hearts were collected either immediately (A1) or
      after an hour (A2) before being subjected to cervical dislocation. Group (B) rats
      were electrically injured instantaneously postmortem, hearts were collected
      immediately (B1) or an hour later (B2) while Group (C) rats were electrified up
      to death, and their hearts were also gathered either immediately (C1) or after an
      hour (C2) from electrocution. Lastly, another group of rats served as a control
      group (Group D). Subgroup (D1): rats were clamped but not electrified, before
      death and another group of rats were clamped but not electrified, after being
      killed by cervical dislocation. Sections from the hearts of all groups were fixed
      in formalin and routinely processed. The c-fos oncogene expression was evaluated
      in all groups by immunohistochemistry. Significant histopathological findings
      were detected in groups A and C. Few c-fos oncogene protein positive
      cardiomyocyte nuclei were seen in rats of groups (A1) and (B1). Additionally,
      increased expression in rats of groups C1, C2 and A2 were observed. On the other
      hand, no c-fos protein expression was seen either in the control (groups D1 and
      D2) or in group B2. Significant differences (p < 0.001) in c-fos expression were
      observed among rats of groups with antemortem electric injury (A1, A2) and those
      of postmortem injury (B1 and B2). Thus, in addition to classical
      histopathological methods, c-fos can be regarded as a target in identifying
      electrical injury, and can be used as an indicator to distinguish antemortem from
      postmortem electric shock.

PMID- 24661706
TI  - Violence against women: profile of the aggressors and victims and
      characterization of the injuries. A forensic study.
AB  - OBJECTIVE: This study, carried out based on examinations of battered women by the
      Clinical Forensic Service of the Afranio Peixoto Medical-Legal Institute in the
      city of Rio de Janeiro, aims to characterize the nature of the injuries suffered
      by victims of domestic violence and to investigate the motivation of such events,
      the family situations in which they occur, the habits of victims and aggressors
      and the social milieu involved. METHOD: A questionnaire was given to 1000
      battered women attended by that service between October 2009 and March 2012,
      along with simultaneous quantification/classification of the injuries suffered.
      RESULTS: We found a prevalence of working women (63.3%), with at least some high
      school (46.6%), who were the main household breadwinners (50.9%). In contrast,
      the largest percentages of male aggressors only had primary school educations at
      most (45.9%), were illegal drug users (60.4%) and were self-employed/freelance
      workers (72.4%). Regarding classification of the injuries (according to the
      Brazilian Penal Code), there were 971 cases of injuries considered slight, 23 of
      severe injuries and 6 of very severe injuries. CONCLUSION: The majority of the
      women studied continue suffering aggressions even though they have their own
      means of support without depending on a male companion or husband. The reasons
      given for accepting the aggressive acts were mainly associated with the
      psychological sphere, in a relation of dependence and subordination.

PMID- 24661707
TI  - Alcohol consumption as a risk factor for sexual assault: a retrospective
      analysis.
AB  - The aim of this study was to establish whether there is a correlation between
      alcohol consumption and reported sexual assaults among young people in the UK. A
      retrospective analysis of all cases between 01/05/2011 and 30/04/2012 involving
      complainants between the ages of 12 and 25 was carried out at the Lancashire SAFE
      Centre. In total 286 cases were included. Case notes were audited for evidence of
      alcohol consumption by the complainant in the 24 h prior to their assault.
      Further information regarding amount of alcohol consumed and any other drugs
      involved was also collected. In total it was found that 70.6% of complainants had
      consumed alcohol before being assaulted. This percentage was noted to vary with
      the complainant's age, ranging from 0% (age 12) to 100% (age 24). Of those who
      had consumed alcohol, complainants in 76.2% of cases had drunk more than the
      recommended daily alcohol intake, and almost a third had also taken drugs. There
      was only one case of suspected covert drug administration, and one forcible drug
      usage; in all other cases alcohol or drugs were taken voluntarily. Stranger rape
      (including where the complainant had known the assailant only briefly, such as
      meeting them the same day) was more common in complainants who had consumed
      alcohol. In summary, alcohol consumption often precedes sexual assaults among
      young people in the UK. This study therefore recommends the more widespread use
      of public awareness campaigns to highlight the risk of rape associated with
      excessive alcohol consumption.

PMID- 24661708
TI  - Misrepresentation of UK homicide characteristics in popular culture.
AB  - The homicide statistics of a popular UK television fictional crime series and the
      former Lothian & Borders police force region, Scotland were compared. This
      comparison was used to consider the implications for public attitudes which may
      influence the adoption of public health interventions to reduce homicide. 217
      homicides were identified by 105 perpetrators in the television series 'Midsomer
      Murders' between 1997 and 2011; these were compared to 55 homicides by 53
      perpetrators in the regional sample between 2006 and 2011. The numbers of serial
      killings (p < 0.0001), planned homicides, female perpetrators (p < 0.0001),
      shootings (p = 0.0456) and poisonings (p = 0.0289) were higher in the fictional
      sample. Lothian & Borders cases were almost all single killings, mostly
      unplanned, with a far greater rate of homicide by kitchen knives (p < 0.0001) and
      hitting/kicking (p = 0.0005) by intoxicated perpetrators. Control of access to
      pointed kitchen knives by members of certain groups may reduce homicide rates. If
      the popular perception of UK homicides is influenced by popular culture, the
      importance of such a public health intervention may not be apparent.

PMID- 24661709
TI  - A molecular forensic method for identifying species composition of processed
      marine mammal meats.
AB  - We used universal primers designed for the cytochrome oxidase I (CO I) sequence
      of the order Cetacea and the family Phocidae to prove that meat fritters sold in
      Taiwan contained meat from two seal, six cetacean, and one pig species. The
      sequence information for CO I obtained in this study was limited and population
      genetics data for the eight sampled marine mammalian species was insufficient to
      deduce where these marine mammals were hunted. Regardless of the geographic
      origins of the marine mammal flesh, sale and consumption of marine mammals in
      Taiwan violates the Wildlife Conservation Act. This study provides PCR primers
      that could enable government testing of suspect meats to curtail the illegal
      trade in marine mammal products. 

PMID- 24661710
TI  - Sexing based on measurements of the femoral head parameters on pelvic
      radiographs.
AB  - BACKGROUND AND AIM: Previous studies have shown that the collo-diaphysial angle
      varies by race and sex in different populations. This study was performed to
      compare the femoral head parameters in the two sexes using pelvic radiography in
      Iranian adults during the August 2011 to August 2012 period. MATERIALS AND
      METHODS: This cross-sectional study was done on 100 male and 100 female. After
      taking hip radiography, collo-diaphysial angle, maximum femoral head diameters
      and minimum femoral neck width were measured on both sides. Dominant hand,
      height, weight and body mass index were also recorded. Data were analyzed using
      SPSS software. Sex differences were tested using independent t-test and ROC
      curve. RESULTS: The mean of the right and left maximum femoral head diameters and
      the minimum width of the femoral neck were significantly higher in men than in
      women (p < 0.001). The mean of the right collo-diaphysial angle of the femur was
      significantly higher in men than in women (p = 0.01), but there was no
      significant difference between the left collo-diaphysial angle in the two sex.
      The accuracy of sex prediction with the right and left maximum femoral head
      diameter was 78%. This figure is 77% for the right and left minimum femoral neck
      widths and 59% for the right collo-diaphysial angle. CONCLUSION: If only the
      proximal part of the femur is available, the sex can be predicted with a
      relatively high accuracy by taking a radiograph. In our study, the evaluation of
      the collo-diaphysial angle was not very helpful in sexing.

PMID- 24661711
TI  - Secondary combined suicide pact.
AB  - This article reports a combined suicide pact, where in a young couple; a 26 year
      old male and a 20 year old female committed suicide by using two methods. The
      couple had resorted to hanging and self-immolation to prevent failure of single
      method alone. In secondary combined suicides, several other methods of suicide
      are tried after the first method chosen has failed. It is primary combined
      suicide only when two or more methods are used simultaneously. Both types of
      combined suicide by one individual is well reported in the literature whereas the
      same by two persons together is rare. In this report, the deceased were
      disappointed lovers, poor and the family members were against their marriage. The
      investigation of scene, methods employed to commit suicide, autopsy findings and
      the interview with their relatives altogether suggested that it was a secondary
      combined suicide pact. 

PMID- 24661712
TI  - Autopsy in Islam and current practice in Arab Muslim countries.
AB  - Autopsy, or post-mortem examination, is the dissection of a dead body. It is
      performed for many reasons. Attitudes toward dead bodies vary with religious
      beliefs and cultural and geographical backgrounds. We have carried out an
      extensive literature review to determine the Islamic view and current practice of
      Autopsy, in at least four Arab countries which published their experiences.
      Several research articles have studied the history of Islamic Autopsy as well as
      the current situation and legal debates about it. The overwhelming conclusion is
      that data is lacking. More must be published from Arabic Muslim countries and
      more research done to correct misconceptions. We also recommend more application
      of non-invasive Autopsy. 

PMID- 24661713
TI  - Hypoxic ischemic brain injury following in hospital cardiac arrest - lessons from
      autopsy.
AB  - Hypoxic ischemic brain injury (HIBI) is the most decisive factor in determining
      the outcome following a cardiac arrest. After an arrest, neuronal death may be
      early or delayed. The aim of our study is to determine the prevalence and
      predictors of HIBI on autopsy following an in hospital cardiac arrest. We
      retrospectively reviewed the medical records of patients who sustained an in
      hospital cardiorespiratory arrest and underwent autopsy following in hospital
      mortality at our tertiary care medical center from January 2004-June 2012. These
      patients were identified from the autopsy registry maintained by the Department
      of Pathology and were classified into two groups based on the presence or absence
      of HIBI on autopsy. We compared the baseline demographics, risk factors, total
      duration of cardiopulmonary resuscitation, number of resuscitative events and
      survival time between both groups. Multivariate logistic regression analysis was
      performed to identify predictors of hypoxic ischemic injury following cardiac
      arrest. Out of 71 patients identified during this study period, 21% had evidence
      of HIBI on autopsy. On univariate analysis, predictors of HIBI were prolonged
      hospital stay, prolonged survival time following an arrest and a slight increased
      trend following multiple resuscitative events. On multivariate analysis,
      prolonged survival time was the only significant predictor of HIBI. Similar to
      other prognostication cardiac arrest studies, there were minimal predictors of
      early neuronal injury even on autopsy. 

PMID- 24661714
TI  - Improving traditional dental autopsies in postmortem examinations of intraoral
      gunshot wounds.
AB  - Despite the recent advances in the post-mortem forensic examinations, some medico
      legal institutes are limited in accessing improved technological facilities,
      hampering an optimal autopsy. Specifically in developing countries, high-cost
      imaging devices are not afforded, making necessary the development of alternative
      autopsy techniques. In parallel, in dental autopsies muscle stiffness is often
      observed lacking mouth opening. This situation is specifically worse in cases of
      intraoral firearm injuries, in which detailed description of the detected wounds
      must be reported post-mortem. Based on this context, the present study aims to
      illustrate two cases of intraoral firearm injuries, in which the dental autopsies
      were performed considering a conservative and alternative technique for the
      improvement of mouth opening. Both cases provided optimal results, indicating the
      new approach as a valuable tool for dental autopsies. 

PMID- 24661715
TI  - Identifying the sexual dimorphism of deciduous dentition in a paediatric South
      Indian population.

PMID- 24661716
TI  - Alcohol and substance use among arrestees examined in police custody.

PMID- 24661717
TI  - Psychogenic non-epileptic seizures - the age matters.

PMID- 24661718
TI  - Replying to the letter entitled 'management of coexistent intracranial aneurysms
      and extracranial carotid atherosclerotic disease'.

PMID- 24661719
TI  - Assessment of elastin degradation as a surrogate measurement of atherosclerotic
      plaque stability.

PMID- 24661720
TI  - Reference ranges of lymphocyte subsets in healthy adults and adolescents with
      special mention of T cell maturation subsets in adults of South Florida.
AB  - BACKGROUND: Analysis of peripheral blood lymphocyte subsets has become an
      essential tool in the evaluation of outcome of diagnostic and research related
      questions in immunological and pathological conditions. Periodic evaluation and
      establishment of normal lymphocyte reference ranges are required in clinical and
      research settings of various immunodeficiency disorders for evaluation of the
      significance of observations. It is also important that age and gender specific
      lymphocyte subset reference ranges should be locally established for meaningful
      comparison and accurate result interpretation as age plays a significant role in
      the development of immune system. METHODS: We performed dual platform flow
      cytometry to determine reference ranges for lymphocyte subsets (CD3, CD4, CD8,
      CD19 [B cells] and CD16+CD56+ [Natural Killer - NK cells]) in 50 adolescents (age
      range: 12-18) and 100 adults (age range: 21-67) along with T cell maturation,
      activation and co-stimulatory molecules in healthy multiracial adult population
      of South Florida. RESULTS: The lymphocyte reference ranges percentages [absolute
      counts - Abs, cells/MUl] unadjusted for gender differences for adolescents are:
      CD3: 49-83 [939-2959]; CD4: 27-53 [467-1563]; CD8: 16-40 [259-1262]; CD19+ B
      cells: 8-31 [169-1297] and CD16+CD56+ NK cells: 3-30 [59-1178] and for adults
      are: CD3: 65-88 [983-3572]; CD4: 26-62 [491-2000]; CD8: 14-44 [314-2,087]; CD19+
      B cells: 2-27 [64-800] and CD16+CD56+ NK cells: 2-27 [27-693]. The ranges for
      CD4:CD8 ratio for adolescents and adults are 0.7-2.6 and 0.6-4.4, respectively.
      Gender based analysis of relative percentages of lymphocyte subsets showed no
      significant differences between adult and adolescent males and females. The mean
      CD4:CD8 ratio was significantly higher in adult females than males (P=0.04) and
      in adolescents this difference was not significant between genders. The mean CD3
      and CD4 T cell percentages were higher and CD19 cell percentages were lower in
      adults compared to adolescents (P<0.0001). Absolute lymphocyte counts showed a
      positive correlation with the absolute counts of CD3+, CD4+, CD8+, CD19+,
      CD16+CD56+, CD45RO+ and CD45RA+ cells (all correlations with P<0.0001 except
      CD45RO [P=0.01] and CD45RA [P=0.03]). CONCLUSION: The reference values of
      peripheral blood lymphocyte subsets were analyzed in healthy adolescent and adult
      population of South Florida. This study indicates the need for periodic
      evaluation and establishment of lymphocyte reference ranges for patient
      population served based on gender and age since these could influence immune
      status and treatment outcome.

PMID- 24661721
TI  - The influence of intrinsic and extrinsic factors on immune system aging.
AB  - Sex and age-matched wild-type and TCR transgenic mice were infected with
      cytomegalovirus (CMV) at 6 months of age and followed for 12 additional months to
      examine aging of the immune system. It was found that viral infection of C57Bl/6
      mice resulted in accelerated aging of the immune system as shown by a loss of
      CD8(+)28(+) cells and an accumulation of KLRG1(+) T cells. CMV infection of OT-1
      transgenic mice had no influence on immune aging of these mice which nonetheless
      demonstrated an accumulation of CD8(+)28(-) and KLRG1(+) T cells with time.
      CD4(+) T cells were unaffected in either strain of mice. Thus, immunological
      aging was found to be due to both cell-intrinsic and cell-extrinsic factors.
      Persistent viral infections may accelerate immunological aging but consideration
      must be given to individual variation in the aging process. 

PMID- 24661722
TI  - Child neglect in one-child families from Suzhou City of mainland China.
AB  - BACKGROUND: The one-child policy introduced in China in 1979 has led to far
      reaching changes in socio-demographic characteristics. Under this policy regime,
      each household has few children. This study aims to describe the prevalence of
      child neglect in one-child families in China and to examine the correlates of
      child neglect. METHODS: A cross-sectional study of 2044 children aged 6 to 9
      years and recruited from four primary schools in Suzhou City, China was
      conducted. Neglect subtypes were determined using a validated indigenous
      measurement scale reported by parents. Child, parental and family characteristics
      were obtained by questionnaires and review of social security records. Linear
      regression analyses were performed to estimate the associations between these
      factors and the subtypes of child neglect. RESULTS: The prevalence of child any
      neglect was 32.0% in one child families in Suzhou City, China. Supervisory
      (20.3%) neglect was the most prevalent type of child neglect, followed by
      emotional (15.2%), physical (11.1%), and educational (6.0%) neglect After
      simultaneous adjustment to child and family characteristics and the school
      factor, boys, children with physical health issues and cognitive impairment,
      younger and unemployed mother, were positively associated with neglect subtypes.
      We also found that parents with higher education and three-generation families
      were negatively associated with neglect. CONCLUSION: The rates of child neglect
      subtypes vary across different regions in China probably due to the different
      policy implementation and socio-economic levels, with a lower level of physical
      and educational neglect and a higher level of emotional neglect in this study.
      The three-generation family structure was correlates of neglect which may be
      unique in one child families. This indicates that future intervention programs in
      one-child families should target these factors.

PMID- 24661723
TI  - Yoga practice in England 1997-2008: prevalence, temporal trends, and correlates
      of participation.
AB  - BACKGROUND: Yoga is a holistic practice that may offer several health benefits.
      No study has examined the prevalence, temporal trends, or correlates of yoga
      practice at the population level in a European country and very few such studies
      exist worldwide. The objective of the study is to examine the prevalence, trends
      and correlates of yoga practice in England between 1997 and 2008. FINDINGS:
      Analysis was conducted in early 2013 using Health Survey for England data.
      Independent cohorts, representative of adults living in England, were surveyed in
      annual cycles in 1997-1999, 2003-2004, and 2006/2008. Prevalence of yoga practice
      (defined as any practice in the past four weeks) was determined at each time
      point and multiple logistic regression was used to examine temporal trends (using
      1997-1999 as reference time point) and the correlates of yoga practice. The
      prevalence of yoga practice was 0.46% (95% CI: 0.39%-0.52%) in 1997-1999, 0.94%
      (0.83%-1.06%) in 2003-2004, and 1.11% (0.95%-1.28%) in 2006/2008. Yoga
      participants in England were more likely to be older, female, degree educated, of
      non-manual social class, lower BMI, better self-rated general health, inactive
      occupation, and higher moderate-to-vigorous physical activity. Adjusted for age,
      sex, social class, and long standing illnesses, there was a significant
      increasing trend of yoga practice from 1997 to 2008 (2003/04 OR = 1.93, 95% CI:
      1.59-2.34; 2006/08 OR = 2.19, 95% CI: 1.77-2.71). CONCLUSIONS: Yoga practice has
      increased in popularity, though the absolute rates are still relatively low.
      Future population studies should more comprehensively examine the contexts,
      settings, styles, correlates and health benefits of yoga practice.

PMID- 24661724
TI  - An improved high-output cell microarray technology.
AB  - AIMS: Cell microarray (CMA) is a high-throughput scientific research tool, which
      has greatly accelerated many analyses based at the cellular level. However, there
      are few described methods for constructing CMAs. Here, we introduce a new,
      simple, high-output CMA method that is applicable to a broad range of cellular
      samples. METHODS: In this method, a recipient block (length, 3.6 cm; width, 2.7
      cm; depth, 2 cm) with 40 dot markers was moulded using a transparent plastic box.
      Adenocarcinoma cells were collected from malignant pleural effusions, cell
      cylinders were moulded with plastic piping and the cylinders were manually
      arrayed one by one into the corresponding location of the 60  degrees C pre
      softened recipient block using the guide holes drilled with a steel needle. We
      constructed a 40-cylinder CMA to prove this method. The expression of cytokeratin
      7 (CK7) in the CMA was examined to confirm antigen preservation and epidermal
      growth factor receptor (EGFR) gene mutation was screened for in five samples.
      RESULTS: The CMA prepared by this method had well-defined array configurations,
      good cellular morphology and well-preserved proteins and DNA. A total of 1000
      sections could be easily gained from this CMA block. CONCLUSIONS: This simple and
      low-cost method provides a novel way of preparing a high-output CMA.

PMID- 24661725
TI  - Adverse events related to gastrointestinal endoscopic procedures in pediatric
      patients under anesthesia care and a predictive risk model (AEGEP Study).
AB  - BACKGROUND: Multiple studies have analyzed perioperative factors related to
      adverse events (AEs) in children who require gastrointestinal endoscopic
      procedures (GEP) in settings where deep sedation is the preferred anesthetic
      technique over general anesthesia (GA) but not for the opposite case. METHODS: We
      reviewed our anesthesia institutional database, seeking children less than 12
      years who underwent GEP over a 5-year period. A logistic regression was used to
      determine significant associations between preoperative conditions,
      characteristics of the procedure, airway management, anesthetic approaches and
      the presence of serious and non-serious AEs. RESULTS: GA was preferred over deep
      sedation [77.8% vs. 22.2% in 2178 GEP under anesthesia care (n=1742)]. We found
      96 AEs reported in 77 patients, including hypoxemia (1.82%), bronchospasm (1.14%)
      and laryngospasm (0.91%) as the most frequent. There were 2 cases of severe
      bradycardia related to laryngospasm/hypoxemia and a case of aspiration resulting
      in unplanned hospitalization, but there were no cases of intra- or postoperative
      deaths. Final predictive model for perioperative AEs included age <1 year, upper
      respiratory tract infections (URTI) <1 week prior to the procedure and low weight
      for the age (LWA) as independent risk factors and ventilation by facial mask as a
      protector against these events (p<0.05). CONCLUSIONS: AEs are infrequent and
      severe ones are remote in a setting where AG is preferred over deep sedation.
      Ventilatory AEs are the most frequent and depend on biometrical and comorbid
      conditions more than anesthetic drugs chosen. Age <1 year, history of URTI in the
      week prior to the procedure and LWA work as independent risk factors for AEs in
      these patients.

PMID- 24661726
TI  - [Breakthrough pain treatment with sublingual fentanyl in patients with chronic
      cutaneous ulcers].
AB  - OBJECTIVE: The aim of the study was to assess the efficacy and safety of opioids
      in the management of pain in those patients with chronic cutaneous ulcers and
      breakthrough/incidental pain. MATERIAL AND METHOD: An open-label, multicentre,
      prospective, uncontrolled study was conducted in the pain and ulcer units of 5
      hospitals across the Comunidad Valenciana. Eligibility criteria were baseline
      pain 4 in the visual analogue scale or breakthrough procedural pain 4. Exclusion
      criteria were cognitive impairment, opioid intolerance, or patient refusal to
      provide informed consent. The protocol scheduled 5 controls: baseline
      (enrolment), 15 days, one month, 2 months, and 3 months. The main outcome measure
      of the study was the visual analogue scale score during rest, movement and
      procedures. Opioids were administered for release of the baseline pain, and
      sublingual fentanyl for breakthrough pain. RESULTS: A total of 32 patients
      (86.5%) completed the study. Baseline pain achieved a mean improvement of 3.6
      visual analogue scale points (SD 2.3), movement pain improved by 3.9 points (SD
      2.5) and procedural pain improved by 4.5 points (SD 2.8), and the mean pain
      intensity improvement was statistically significant from the first control and at
      all controls thereafter (P<.001). Nausea was reported by 14 patients (43.8%),
      drowsiness and constipation by 7 (21.9%), itching by 5 (15.6%), and one (3.1%)
      reported vomiting. CONCLUSIONS: Structured assessment of pain is a key concept in
      the management of patient with chronic cutaneous ulcers. The results of this
      study suggest that opioid therapy provides clinically significant pain relief
      with few adverse effects.

PMID- 24661727
TI  - Single-access laparoscopic rectal cancer surgery using the glove technique.
AB  - INTRODUCTION: Single-access laparoscopic surgery has been widely adopted in many
      kinds of surgery including laparoscopic cholecystectomy and laparoscopic
      colectomy. Performing single-access rectal surgery, however, has technical
      drawbacks such as instrument collision and endostaple application issues. The
      glove technique is likely to mitigate these problems. METHODS: Fourteen patients
      with anal canal to mid-rectum cancers were recruited and underwent single-access
      laparoscopic surgery via the glove technique. An incision was made at the
      paraumbilicus to insert a wound protector with surgical gloves. The operation was
      medial to lateral and inferior mesenteric artery and inferior mesenteric vein
      were identified and controlled. Total mesorectal excision was performed while
      keeping traction and countertraction down to the pelvic floor. RESULTS: Average
      operative time was 251.66 min (range, 180-300 min). Hospital stay ranged from 5
      to 8 days (median, 7 days). No serious early postoperative surgical problems
      related to complications were observed. The pathologic results showed good
      mesorectal capsule grading. The mean lymph node harvest was 14 nodes (range, 7-26
      nodes), and the mean wound length was 5 cm (range, 4-6 cm). CONCLUSIONS: In
      rectal surgery, the glove technique for single-access laparoscopic surgery is
      feasible and is comparable to commercial single-port techniques in terms of
      oncologic results.

PMID- 24661728
TI  - SK channel blockade reverses cognitive and motor deficits induced by
      nigrostriatal dopamine lesions in rats.
AB  - Parkinson's disease has traditionally been viewed as a motor disorder caused by
      the loss of dopamine (DA) neurons. However, emotional and cognitive syndromes can
      precede the onset of the motor deficits and provide an opportunity for
      therapeutic intervention. Potassium channels have recently emerged as potential
      new targets in the treatment of Parkinson's disease. The selective blockade of
      small conductance calcium-activated K+ channels (SK channels) by apamin is known
      to increase burst firing in midbrain DA neurons and therefore DA release. We thus
      investigated the effects of systemic administration of apamin on the motor,
      cognitive deficits and anxiety present after bilateral nigrostriatal 6
      hydroxydopamine (6-OHDA) lesions in rats. Apamin administration (0.1 or 0.3 mg/kg
      i.p.) counteracted the depression, anxiety-like behaviors evaluated on sucrose
      consumption and in the elevated plus maze, social recognition and spatial memory
      deficits produced by partial 6-OHDA lesions. Apamin also reduced asymmetric motor
      deficits on circling behavior and postural adjustments in the unilateral
      extensive 6-OHDA model. The partial 6-OHDA lesions (56% striatal DA depletion)
      produced 20% decrease of iodinated apamin binding sites in the substantia nigra
      pars compacta in correlation with the loss of tyrosine hydroxylase positive
      cells, without modifying apamin binding in brain regions receiving DAergic
      innervation. Striatal extracellular levels of DA, not detectable after 6-OHDA
      lesions, were enhanced by apamin treatment as measured by in vivo microdialysis.
      These results indicate that blocking SK channels may reinstate minimal DA
      activity in the striatum to alleviate the non-motor symptoms induced by partial
      striatal DA lesions. 

PMID- 24661729
TI  - Precision of progesterone measurements with the use of automated immunoassay
      analyzers and the impact on clinical decisions for in vitro fertilization.
AB  - OBJECTIVE: To compare the precision of progesterone measurements obtained with
      the use of immunoassays and of liquid chromatography-tandem mass spectrometry (LC
      MS/MS). DESIGN: Comparative study. SETTING: Academic, private practice, and in
      vitro fertilization (IVF) research centers. PATIENT(S): A total of 189 human
      serum samples were collected during controlled ovarian hyperstimulation and early
      pregnancy in women undergoing IVF. INTERVENTION(S): Serum progesterone pools (n =
      10; 0.2-4 ng/mL) were sent to four laboratory centers that used four different
      automated immunoassay analyzers. Progesterone was measured by immunoassay in
      triplicate at three separate time points (n = 9 per pool) and by LC-MS/MS in
      triplicate once (n = 3 per pool). MAIN OUTCOME MEASURE(S): Inter- and intraassay
      coefficients of variation (CVs) of progesterone measurements were compared for
      each analyzer and LC-MS/MS. RESULT(S): Progesterone measurements by immunoassay
      were highly correlated with those by LC-MS/MS. Only two analyzers had intraassay
      CVs <10% at all three experimental time points, and only two analyzers had an
      interassay CV <10%. Mean progesterone levels by the analyzers were different
      across multiple progesterone pools. CONCLUSION(S): Our results indicate that
      progesterone threshold measurements used for IVF clinical decisions should be
      interpreted cautiously and based on laboratory- and method-specific data. A
      validated progesterone standard incorporated into daily immunoassays could
      improve medical decision accuracy.

PMID- 24661730
TI  - Genetic variants in Ser-Arg protein-coding genes are associated with the risk of
      nonobstructive azoospermia in Chinese men.
AB  - OBJECTIVE: To evaluate the association between genetic variants in Ser-Arg (SR)
      protein-coding genes and the susceptibility of nonobstructive azoospermia (NOA)
      in Chinese men. DESIGN: Case-control study. SETTING: State Key Laboratory of
      Reproductive Medicine in Nanjing Medical University conducted the genotyping and
      examined the expression levels of genes. PATIENT(S): The study included 962 NOA
      patients and 1,931 control subjects. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Genotyping of 16 single-nucleotide polymorphisms (SNPs) of eight
      "canonic" SR protein-coding genes were performed with the use of the Illumina
      Infinium Beadchip platform. Odds ratios were calculated by logistic regression
      analysis in the additive model. Expression levels were measured by quantitative
      reverse-transcription polymerase chain reaction. RESULT(S): Rs17431717 near SFRS9
      and rs12046213 near SFRS4 were significantly associated with a decreased risk of
      NOA, whereas rs10849753 near SFRS9 and rs6103330 in SFRS6 were associated with an
      increased risk of NOA. Of the two SNPs in SFRS9, only rs17431717 remained
      significant after conditioning on another. Combined analysis of three promising
      SNPs (rs17431717, rs12046213, and rs6103330) showed that compared with
      individuals with "0-2" risk alleles, those carrying "3," "4," and ">= 5" risk
      alleles had 1.22-, 1.38-, and 1.90-fold increased risk of NOA, respectively.
      CONCLUSION(S): Polymorphisms in SR protein-coding genes may contribute to the
      risk of NOA in Chinese men. The findings of this study can help us to further
      understand the etiology of spermatogenic impairment, and they provide more
      evidence for the role of splicing activity in human spermatogenesis.

PMID- 24661731
TI  - The WNT/beta-catenin signaling pathway and expression of survival promoting genes
      in luteinized granulosa cells: endometriosis as a paradigm for a dysregulated
      apoptosis pathway.
AB  - OBJECTIVE: To analyze the WNT/beta-catenin signaling pathway in luteinized
      granulosa cells from women with and without endometriosis in relation to cellular
      apoptosis. DESIGN: Basic. SETTING: University hospital. PATIENT(S): Patients with
      a laparoscopic diagnosis of endometriosis (n = 30) and women undergoing
      intracytoplasmic sperm injection for male infertility (control group n = 39).
      INTERVENTION(S): Isolation of luteinized granulosa cells. MAIN OUTCOME
      MEASURE(S): Gene expression analysis of components of the WNT/beta-catenin
      pathway, protein expression levels of beta-catenin, and cell cycle studies in
      luteinized granulosa cells. RESULT(S): Compared with luteinized granulosa cells
      from control women, cells derived from endometriosis patients had significantly
      higher transcript levels of the beta-catenin-independent molecules WNT4 and WNT5a
      and lower levels of the beta-catenin-dependent molecule WNT1. A decrease of total
      beta-catenin as well as of its dephosphorylated active form, together with an
      aberrant gene expression of the downstream targets survivin and BMP4, was
      detected in cells from affected women. Flow cytometry analysis confirmed an
      enhanced apoptosis of luteinized granulosa cells from patients with
      endometriosis. CONCLUSION(S): The concomitant dysregulation of specific members
      of the WNT pathway and of its pivot molecule beta-catenin in granulosa cells
      characterized by an increased apoptosis suggests that the WNT/beta-catenin
      signaling pathway might be involved in leading to granulosa cell atresia.

PMID- 24661732
TI  - Ovarian morphology assessed by magnetic resonance imaging in women with and
      without polycystic ovary syndrome and associations with antimullerian hormone,
      free testosterone, and glucose disposal rate.
AB  - OBJECTIVE: To characterize ovarian morphology and perfusion by magnetic resonance
      imaging (MRI) in women with and without polycystic ovary syndrome (PCOS) and to
      investigate associations with antimullerian hormone (AMH), free T, and glucose
      disposal rate (GDR). DESIGN: Explorative cross-sectional study. SETTING:
      University hospital. PATIENT(S): Fifty-eight women with PCOS and 31 controls from
      the general population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Antral
      follicle count (AFC), ovarian/stromal volume, perfusion, AMH, free T, and GDR.
      RESULT(S): Antral follicles of 1-3 and 4-6 mm, but not 7-9 mm, were more
      numerous, and total AFC (1-9 mm) was higher in women with PCOS. Ovarian volume
      was larger in women with PCOS. AMH and free T were higher and GDR was lower in
      women with PCOS. All values were more deranged in classic compared with
      nonclassic PCOS. There was a positive correlation between AMH and AFC, 1-3 mm (r
      = 0.81), and between AMH and total AFC (r = 0.87). In receiver operating
      characteristic analyses, the area under the curve was 0.89 for total AFC, 0.86
      for AMH, and 0.90 for free T. PCOS was independently associated with AFC and free
      T but not with AMH or GDR when adjusted for age and body mass index.
      CONCLUSION(S): Counting antral follicles down to 1 mm in size by MRI yielded
      higher AFCs than previously reported. AFC, AMH, and free T discriminated with
      high accuracy between women with PCOS and controls, but AMH was not independently
      associated with PCOS. CLINICAL TRIAL REGISTRATION NUMBER: NCT00484705.

PMID- 24661734
TI  - [What to eat and drink in glaucoma? Evidence from human studies].

PMID- 24661733
TI  - Elevated expression of CD147 in patients with endometriosis and its role in
      regulating apoptosis and migration of human endometrial cells.
AB  - OBJECTIVE: To examine the expression of CD147 in 60 human endometriosis lesions
      and how CD147 regulates migration and apoptosis in human uterine epithelial
      (HESs) cells. DESIGN: Experimental clinical study and laboratory-based
      investigation. SETTING: Hospital and academic research center. PATIENT(S): Sixty
      women with chocolate cysts and 16 control women without endometriosis.
      INTERVENTION(S): Human uterine epithelial cells were treated with anti-CD147
      antibody. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction for
      detecting CD147 expression in 60 human endometriosis lesions; migration assay and
      CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS) assay for cell
      functional investigation; Western blot for detecting protein levels; gelatin
      zymography for evaluating the activity of matrix metalloproteinase-2 (MMP-2) in
      cultured cells. RESULT(S): Expression of CD147 was significantly higher in
      ectopic endometrial tissues from patients with endometriosis than in normal
      endometrial tissues. Interference with CD147 function led to decreased migration
      and cell viability in HESs cells. Surprisingly, MMP-2 expression and activity
      were not changed after treating HESs cells with anti-CD147 antibody. Further
      examination revealed that immunodepletion of CD147 induced apoptosis in HESs
      cells, leading to the activation of caspase 3 and poly(ADP-ribose) polymerase.
      CONCLUSION(S): The results of the present study suggest that abnormally high
      expression of CD147 in ovarian endometriosis lesions with enhanced cell survival
      (reduced apoptosis) and migration, in an MMP-2-independent manner, may underlie
      the progression of endometriosis in humans.

PMID- 24661735
TI  - Sexual behaviors and risk for sexually transmitted infections among teenage men
      who have sex with men.
AB  - OBJECTIVES: To report on sexual behaviors and sexually transmitted infections
      (STIs) among men who have sex with men (MSM) in their teens, when many MSM engage
      in their first sexual experiences. METHODS: MSM aged 16 to 20 years were
      recruited via community and other sources. Men completed a questionnaire about
      their sexual behaviors and were screened for gonorrhea, chlamydia, syphilis, and
      HIV. RESULTS: Two hundred men were included. The median age was 19 years. The
      median age at first insertive or receptive anal intercourse was 17 years. Half of
      men reported sex with mainly older men: these men were more likely to engage in
      receptive anal intercourse (48% vs. 25%, p < .001) than other men. Most men had
      engaged in insertive (87%) and receptive (85%) anal intercourse in the prior 12
      months with 60% and 53% reporting inconsistent condom use with insertive and
      receptive anal intercourse partners, respectively. The median number of insertive
      anal intercourse partners was 3 and 1.5 (p < .001) among men reporting
      inconsistent and consistent condom use with insertive anal intercourse over the
      prior 12 months. The median number of receptive anal intercourse partners was 3
      and 2 (p = .006) among men reporting inconsistent and consistent condom use with
      receptive anal intercourse over the prior 12 months. Pharyngeal gonorrhea, rectal
      gonorrhea, urethral chlamydia, rectal chlamydia, and syphilis were detected in
      3.0%, 5.5%, 3.0%, 4%, and 2.0% of men, respectively. All men were HIV negative.
      CONCLUSION: Many of the teenage MSM in this study were at risk for STI.
      Preventative messages and STI screening interventions that are age appropriate
      need to be developed to reduce HIV and STI risk in this under-recognized group.

PMID- 24661736
TI  - Alcohol use trajectories after high school graduation among emerging adults with
      type 1 diabetes.
AB  - OBJECTIVE: To explore alcohol involvement trajectories and associated factors
      during the year post-high school (HS) graduation among emerging adults with type
      1 diabetes. METHODS: Youth (N = 181) self-reported alcohol use at baseline and
      every 3 months for 1 year post-HS graduation. Data were also collected on parent
      youth conflict, diabetes self-efficacy, major life events, living and educational
      situations, diabetes management, marijuana use, cigarette smoking, and glycemic
      control. Trajectories of alcohol use were modeled using latent class growth
      analysis. Associations between trajectory class and specific salient variables
      were examined using analysis of variance, chi square, or generalized linear mixed
      model, as appropriate. RESULTS: Identified alcohol involvement trajectory classes
      were labeled as (1) consistent involvement group (n = 25, 13.8%) with stable,
      high use relative to other groups over the 12 months; (2) growing involvement
      group (n = 55, 30.4%) with increasing use throughout the 12 months; and (3)
      minimal involvement group (n = 101, 55.8%) with essentially no involvement until
      the ninth month. Those with minimal involvement had the best diabetes management
      and better diabetes self-efficacy than those with consistent involvement. In
      comparison with those minimally involved, those with growing involvement were
      more likely to live independently of parents; those consistently involved had
      more major life events; and both the growing and consistent involvement groups
      were more likely to have tried marijuana and cigarettes. CONCLUSIONS: This sample
      of emerging adults with type 1 diabetes has three unique patterns of alcohol use
      during the first year after HS.

PMID- 24661737
TI  - Outcomes and resource utilization associated with underage drinking at a level I
      trauma center.
AB  - PURPOSE: To examine the association of blood alcohol content (BAC) on hospital
      based outcomes and imaging utilization for patients <21 years admitted to a level
      I trauma center. METHODS: Retrospective analysis of alcohol-involved injuries in
      patients 13-20 years, admitted to a level I trauma center from 1996 to 2010. An
      injury was considered alcohol involved if the patient had a BAC > 0.
      Multivariable logistic regression was used to compare mortality, discharge
      destination (home and skilled nursing facility), intensive care unit admission,
      and operating room use between patients with and without positive BAC for
      patients 13-15, 16-17, and 18-20 years. Multivariable linear regression was used
      to compare length of hospitalization. Finally, multivariable negative binomial
      regression evaluated radiology resource utilization (x-ray, computed tomography
      [CT], and magnetic resonance imaging). RESULTS: A total of 7,663 patients, 13-20
      years old, were admitted over the study period. A positive BAC was reported in
      19% of these patients. In general, the presence of alcohol was not associated
      with mortality rate, length of hospitalization, intensive care unit, and
      operating room use or discharge status for any age group. However, the presence
      of alcohol was associated with higher utilization of head (incidence rate ratio
      [IRR] 1.13, 95% confidence interval [CI] 1.02-1.26), cervical spine (IRR 1.10,
      95% CI 1.01-1.22), and thoracic (IRR 1.30, 95% CI 1.05-1.63) CTs in young adults
      18-20 years. No differences in CT use were observed in patients 13-15 or 16-17
      years. CONCLUSIONS: Positive BAC was not significantly associated with adverse
      outcomes or resource utilization in younger trauma patients. However, the use of
      certain body region CTs was associated with positive BAC in patients 18-20 years.

PMID- 24661738
TI  - Direct-to-consumer tobacco marketing and its association with tobacco use among
      adolescents and young adults.
AB  - OBJECTIVE: We assess exposure to direct-to-consumer tobacco marketing and its
      association with ever having tried smoking, smoking within past 30 days
      (current), and smoking >=100 cigarettes in lifetime (established) among
      adolescents and young adults. METHODS: We surveyed a U.S. telephone sample of
      3,342 15- to 23-year-olds and 2,541 respondents subsequently completed a web
      based survey. Among respondents completing both the telephone and web-based
      surveys (N = 2,541 [75%]), we assessed their exposure to direct-to-consumer
      tobacco marketing (receiving direct mail from tobacco companies and seeing
      tobacco company websites) and their associations with ever having tried smoking,
      current smoking, and established smoking. RESULTS: Overall, 12% of 15- to 17-year
      olds and 26% of 18- to 23-year-olds were exposed to direct-to-consumer tobacco
      marketing. Racial/ethnic minority nonsmoking respondents were more likely to see
      tobacco websites than nonsmoking whites. Respondents exposed to either form of
      direct-to-consumer tobacco marketing were more likely to currently smoke
      (adjusted odds ratio 2.2, 95% confidence interval 1.3-3.8), while those exposed
      to both forms of marketing experienced even higher odds of currently smoking
      (adjusted odds ratio 2.7, 95% confidence interval 1.1-6.6). We observed similar
      relationships for ever having tried smoking and established smoking. CONCLUSIONS:
      Direct-to-consumer tobacco marketing reaches adolescent and young adult
      nonsmokers and is associated with smoking behavior.

PMID- 24661739
TI  - Vitamin D status and its association with season, hospital and sepsis mortality
      in critical illness.
AB  - INTRODUCTION: Vitamin D plays a key role in immune function. Deficiency may
      aggravate the incidence and outcome of infectious complications in critically ill
      patients. We aimed to evaluate the prevalence of vitamin D deficiency and the
      correlation between serum 25-hydroxyvitamin D (25(OH) D) and hospital mortality,
      sepsis mortality and blood culture positivity. METHODS: In a single-center
      retrospective observational study at a tertiary care center in Graz, Austria, 655
      surgical and nonsurgical critically ill patients with available 25(OH) D levels
      hospitalized between September 2008 and May 2010 were included. Cox regression
      analysis adjusted for age, gender, severity of illness, renal function and
      inflammatory status was performed. Vitamin D levels were categorized by month
      specific tertiles (high, intermediate, low) to reflect seasonal variation of
      serum 25(OH) D levels. RESULTS: Overall, the majority of patients were vitamin D
      deficient (<20 ng/ml; 60.2%) or insufficient (>=20 and <30 ng/dl; 26.3%), with
      normal 25(OH) D levels (>30 ng/ml) present in only 13.6%. The prevalence of
      vitamin D deficiency and mean 25(OH) D levels was significantly different in
      winter compared to summer months (P <0.001). Hospital mortality was 20.6% (135 of
      655 patients). Adjusted hospital mortality was significantly higher in patients
      in the low (hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.31 to 3.22)
      and intermediate (HR 1.92, 95% CI 1.21 to 3.06) compared to the high tertile.
      Sepsis was identified as cause of death in 20 of 135 deceased patients (14.8%).
      There was no significant association between 25(OH) D and C-reactive protein
      (CRP), leukocyte count or procalcitonin levels. In a subgroup analysis (n = 244),
      blood culture positivity rates did not differ between tertiles (23.1% versus
      28.2% versus 17.1%, P = 0.361). CONCLUSIONS: Low 25(OH) D status is significantly
      associated with mortality in the critically ill. Intervention studies are needed
      to investigate the effect of vitamin D substitution on mortality and sepsis rates
      in this population.

PMID- 24661740
TI  - Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with
      cirrhosis and ascites.
AB  - BACKGROUND & AIMS: The modulation of gut flora constitutes a therapeutic tool in
      patients with liver disease, but some of its modalities require further
      investigation. Here, we evaluated the effects of probiotics on the hepatic and
      systemic haemodynamic alterations of advanced liver disease. METHODS: Seventeen
      patients with cirrhosis and ascites were prospectively included, five of whom
      abandoned this study prematurely. Hepatic and systemic haemodynamic evaluations
      were performed at baseline and after 6 weeks of receiving an oral VSL#3 probiotic
      preparation. Peripheral blood analyses included the evaluation of cytokines (TNF
      alpha, IL-1beta, IL-6), bacterial translocation [bacterial DNA and
      lipopolysaccharide-binding protein (LBP)] and nitric oxide end-products (NOx).
      RESULTS: In 12 patients completing this study, the oral administration of VSL#3
      resulted in reductions of the hepatic venous pressure gradient (HVPG, P < 0.001),
      cardiac index and heart rate (both P < 0.01) and in increases of the systemic
      vascular resistance (P < 0.05) and mean arterial pressure (P = 0.06). HVPG
      decreased at least 10% from baseline in eight patients (67%). Serum sodium
      increased in most patients (P < 0.01). All these changes were unrelated to the
      detection of bacterial DNA or to the levels of LBP, pro-inflammatory cytokines or
      NOx. No significant adverse effects were observed. CONCLUSION: Administration of
      the probiotic mixture VSL#3 improved the hepatic and systemic haemodynamics and
      serum sodium levels in patients with cirrhosis. Our results identify major
      effects of probiotics in liver disease and provide the rationale for assessing
      their therapeutic potential against the progression of portal hypertension and
      its complications in future clinical trials.

PMID- 24661742
TI  - Cap and trade schemes on waste management: a case study of the landfill allowance
      trading scheme (LATS) in England.
AB  - The Landfill Allowance Trading Scheme (LATS) is one of the main instruments used
      in England to enforce the landfill diversion targets established in the Directive
      1999/31/EC of the European Parliament and of the Council of 26 April 1999 on the
      landfill of waste (Landfill Directive). Through the LATS, biodegradable municipal
      waste (BMW) allowances for landfilling are allocated to each local authority,
      otherwise known as waste disposal authorities (WDAs). The quantity of landfill
      allowances received is expected to decrease continuously from 2005/06 to 2019/20
      so as to meet the objectives of the Landfill Directive. To achieve their
      commitments, WDAs can exchange, buy, sell or transfer allowances among each
      other, or may re-profile their own allocation through banking and/or borrowing.
      Despite the goals for the first seven years - which included two target years
      (2005/06 and 2009/10) - being widely achieved (the average allocation of
      allowances per WDA was 22.9% higher than those finally used), market activity
      among WDAs was high and prices were not very stable. Results in terms of waste
      reduction and recycling levels have been satisfactory. The reduction of BMW
      landfilled (in percentage) was higher during the first seven years of the LATS
      period (2005/06-2011/12) (around 7% annually) than during the previous period
      (2001/02-2004/05) (4.2% annually). Since 2008, the significance of the LATS
      diminished because of an increase in the rate of the UK Landfill Tax. The LATS
      was suppressed after the 2012/13 target year, before what it was initially
      scheduled. The purpose of this paper is to describe the particularities of the
      LATS, analyse its performance as a waste management policy, make a comparison
      with the Landfill Tax, discuss its main features as regards efficiency,
      effectiveness and the application of the "polluter pays" principle and finally
      discuss if the effect of the increase in the Landfill Tax is what made the LATS
      ultimately unnecessary. 

PMID- 24661741
TI  - Comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals
      extensive genetic multiplicity.
AB  - BACKGROUND: Mycobacteria comprise diverse species including non-pathogenic,
      environmental organisms, animal disease agents and human pathogens, notably
      Mycobacterium tuberculosis. Considering that the mycobacterial cell wall
      constitutes a significant barrier to drug penetration, the aim of this study was
      to conduct a comparative genomics analysis of the repertoire of enzymes involved
      in peptidoglycan (PG) remodelling to determine the potential of exploiting this
      area of bacterial metabolism for the discovery of new drug targets. RESULTS: We
      conducted an in silico analysis of 19 mycobacterial species/clinical strains for
      the presence of genes encoding resuscitation promoting factors (Rpfs), penicillin
      binding proteins, endopeptidases, L,D-transpeptidases and N-acetylmuramoyl-L
      alanine amidases. Our analysis reveals extensive genetic multiplicity, allowing
      for classification of mycobacterial species into three main categories, primarily
      based on their rpf gene complement. These include the M. tuberculosis Complex
      (MTBC), other pathogenic mycobacteria and environmental species. The complement
      of these genes within the MTBC and other mycobacterial pathogens is highly
      conserved. In contrast, environmental strains display significant genetic
      expansion in most of these gene families. Mycobacterium leprae retains more than
      one functional gene from each enzyme family, underscoring the importance of
      genetic multiplicity for PG remodelling. Notably, the highest degree of
      conservation is observed for N-acetylmuramoyl-L-alanine amidases suggesting that
      these enzymes are essential for growth and survival. CONCLUSION: PG remodelling
      enzymes in a range of mycobacterial species are associated with extensive genetic
      multiplicity, suggesting functional diversification within these families of
      enzymes to allow organisms to adapt.

PMID- 24661743
TI  - Living with heart failure: psychosocial resources, meaning, gratitude and well
      being.
AB  - OBJECTIVES: The present study explored the experiences of people living with
      advanced heart failure (HF) to determine the extent to which (1) psychosocial
      resources relevant to HF patients were qualitatively reported, and (2) to
      determine the extent to which psychosocial resources were correlates of
      subsequent well-being as assessed by validated quantitative measures. BACKGROUND:
      HF is a serious life-limiting illness that involves impaired heart functionality.
      Patients commonly face severe physical fatigue and frequently endure disabling
      depression. Individuals with HF often report the use of social support and
      religion/spirituality (R/S) as helpful, but little work has systematically linked
      their reliance on these resources and well-being. METHODS: 111 participants
      completed four open-ended questions to assess aspects of living with HF. Open
      ended questions were coded to identify psychosocial resources: positive meaning,
      gratitude, R/S, social support, and medical resources. Data were collected once
      and then again 3 months later. Participants also completed measures of well
      being, including religious meaning, life meaning, satisfaction with life,
      depressive symptoms, death anxiety, and health-related quality of life. Bivariate
      correlations were used to relate psychosocial resources and well-being. RESULTS:
      Patients reported many psychosocial resources, particularly positive meaning,
      R/S, social support, and medical resources. Positive meaning and R/S were
      inversely linked with depressive symptoms. R/S was also related to less death
      anxiety, while social support was related to higher anxiety about death three
      months later. CONCLUSIONS: Findings advance our understanding of the struggles HF
      patients experience and the roles of psychosocial resources such as meaning and
      gratitude in alleviating these struggles. Results may help explain how resources
      like R/S and social support may influence well-being.

PMID- 24661744
TI  - Analysis of 35 cases of Xanthogranulomatous pyelonephritis.
AB  - BACKGROUND: To retrospectively determine key demographic and clinical features of
      35 patients with Xanthogranulomatous pyelonephritis (XGP) in a New Zealand
      setting and to compare it with the existing literature. METHODS: A retrospective
      review of patients having a confirmed diagnosis of XGP on histopathology
      examination was performed. Key clinical and demographic features were analysed
      and compared with the published literature. RESULTS: XGP was diagnosed in 35
      patients over a 12-year (2001-2013) period in Auckland Public Hospital. Ninety
      one percent of the patients were female. The population had significantly higher
      numbers of Maori and Pacific Island patients compared with the general population
      (74%). Staghorn calculi were the most common cause (51.4%) with obstructing
      ureteric calculi as the next most common (22.9%) cause. Twenty percent of cases
      were not thought to be XGP prior to nephrectomy (suspicious renal mass). Thirteen
      (38%) patients suffered serious complications post-operatively (Clavien 3-5).
      CONCLUSION: XGP is a rare chronic inflammatory condition that appears to be
      overrepresented by Maori and Pacific islanders in our cohort when compared with
      the overall patient pool. Surgical treatment is associated with significant
      morbidity but remains the only definitive option. Obesity and other conditions
      associated with metabolic syndrome may coexist at the time of presentation and
      may be contributing factors to the development of XGP and poor outcomes
      associated with it.

PMID- 24661745
TI  - The AAT1 locus is critical for the biosynthesis of esters contributing to 'ripe
      apple' flavour in 'Royal Gala' and 'Granny Smith' apples.
AB  - The 'fruity' attributes of ripe apples (Malus * domestica) arise from our
      perception of a combination of volatile ester compounds. Phenotypic variability
      in ester production was investigated using a segregating population from a 'Royal
      Gala' (RG; high ester production) * 'Granny Smith' (GS; low ester production)
      cross, as well as in transgenic RG plants in which expression of the alcohol acyl
      transferase 1 (AAT1) gene was reduced. In the RG * GS population, 46 quantitative
      trait loci (QTLs) for the production of esters and alcohols were identified on 15
      linkage groups (LGs). The major QTL for 35 individual compounds was positioned on
      LG2 and co-located with AAT1. Multiple AAT1 gene variants were identified in RG
      and GS, but only two (AAT1-RGa and AAT1-GSa) were functional. AAT1-RGa and AAT1
      GSa were both highly expressed in the cortex and skin of ripe fruit, but AAT1
      protein was observed mainly in the skin. Transgenic RG specifically reduced in
      AAT1 expression showed reduced levels of most key esters in ripe fruit.
      Differences in the ripe fruit aroma could be perceived by sensory analysis. The
      transgenic lines also showed altered ratios of biosynthetic precursor alcohols
      and aldehydes, and expression of a number of ester biosynthetic genes increased,
      presumably in response to the increased substrate pool. These results indicate
      that the AAT1 locus is critical for the biosynthesis of esters contributing to a
      'ripe apple' flavour. 

PMID- 24661746
TI  - Mucocutaneous Leishmania tropica infection in a dog from a human cutaneous
      leishmaniasis focus.
AB  - BACKGROUND: Leishmania tropica is a causative agent of cutaneous leishmanaisis in
      the Middle East, North Africa and parts of southeastern Europe. Although
      transmission of L. tropica has been reported as anthroponotic, in Israel it was
      found to have a zoonotic pattern. FINDINGS: A one year old male Pekingese dog
      from Maale Adumim, a focus of L. tropica human cutaneous leishmaniasis near
      Jerusalem, was presented by its owner with a large proliferative red
      mucocutaneous lesion on the lip between the mouth and nose. Physical examination
      and a biochemistry panel were normal and a complete blood count showed mild
      leukocytosis with lymphocytosis and eosinophilia. A biopsy of the lesion was
      suggestive of the presence of Leishmania organisms. Serology for Leishmania sp.
      by ELISA was positive and an aspirate from the lesion showed a large number of
      Leishmania amastigotes. ITS1-HRM-PCR of the lesion was positive and sequencing
      indicated that infection was caused by L. tropica, which was also cultured from
      the lesion. Blood PCR was negative. The dog responded well to allopurinol
      treatment and its lesion shrunk considerably within one month of therapy and
      healed after two months. CONCLUSIONS: Only a few cases of dog infection with L.
      tropica have been described to date. They were reported from Morocco and Iran and
      involved infection of visceral organs. This is the first report of focal
      mucocutaneous L. tropica infection in a dog and its response to anti-leishmanial
      treatment. Domestic and wild canines should be evaluated for being possible
      animal reservoirs for human L. tropica infection in endemic areas or merely
      accidental hosts.

PMID- 24661747
TI  - Southern rice black-streaked dwarf virus (SRBSDV) directly affects the feeding
      and reproduction behavior of its vector, Sogatella furcifera (Horvath)
      (Hemiptera: Delphacidae).
AB  - BACKGROUND: Southern rice black-streaked dwarf virus (SRBSDV) is a recently
      discovered member of the genus Fijivirus and it is transmitted by the rice
      whitebacked planthopper (WBPH), Sogatella furcifera (Horvath). It was found that
      SRBSDV infected vectors might contribute negatively to the WBPH population,
      although the longer nymphal period might benefit viral acquisition, transmission
      and increase infection rate. The interaction between SRBSDV and its vector need
      to be further explored to gain better understanding of the dispersal of WBPH and
      the spread of virus disease, in particular the feeding and reproduction behavior
      of viruliferous WBPH. METHODS: Newly hatched nymphs of WBPH were fed on healthy
      rice plant after feeding on SRBSDV-infected rice plants for 2 h, and newly
      emerged adults were numbered and tested. Feeding behaviors of WBPH adults were
      monitored electronically within a Faraday cage using a Giga-4 DC EPG amplifier.
      The newly emerged adults were paired, and the fecundity and egg hatchability were
      investigated. WBPH was molecularly identified for SRBSDV when they dead.
      According to the identification results, data on viruliferous and non
      viruliferous WBPH were collected and analyzed. RESULTS: Feeding behavior of
      viruliferous WBPH was different from those of non-viruliferous WBPH. Frequency of
      phloem sap ingestion of viruliferous WBPH increased significantly, however the
      total feeding duration did not increase markedly. When both WBPH parents were
      infected with SRBSDV, their fecundity and hatchability of the eggs produced were
      significant lower than those of normal WBPH parents. However, if only one of the
      parents was viruliferous, fecundity and egg hatchability were only slightly
      affected. CONCLUSIONS: Viruliferous WBPH fed on the phloem more frequently than
      non-viruliferous WBPH and can thus contribute to virus transmission. When both
      vector parents are viruliferous fecundity and hatchability of the eggs were
      significantly reduced. However when only one of the parents WBPH was
      viruliferous, there were no significant effects.

PMID- 24661749
TI  - Association of dysfunctional uterine bleeding with high body mass index and
      obesity as a main predisposing factor.
AB  - BACKGROUND: Dysfunctional uterine bleeding (DUB) defined as abnormal uterine
      bleeding in the absence of underlying structural abnormalities. Recently, obesity
      has been suggested as a main underling risk factor for DUB; however, evidences on
      the role of this predisposing factor are not adequate. The current study aimed to
      assess status of obesity in women who suffered from DUB. METHODS: In an
      observational case series study conducted at a referral endocrinology clinic in
      Shahrood city, Samnan, 20 consecutive women with the final diagnosis of DUB
      referred from 2009 to 2011 were evaluated. Obesity was assessed using calculation
      of body mass index (BMI) and waist circumference. RESULTS: The mean waist
      circumference was estimated 102.95+/-9.77 cm in the range of 90-119 cm. With
      respect to BMI measurement, the mean of BMI was 32.63+/-3.34 kg/m(2) ranged
      between 26.92 and 39.06 that two-third of studied women suffered from overweight
      status and other one-third cases were obese. CONCLUSION: There is a strong
      association between obesity and DUB and therefore weight reduction should be
      considered as a conservative treatment besides of other medical or surgical
      treatment approaches.

PMID- 24661748
TI  - Financial management of a large multisite randomized clinical trial.
AB  - BACKGROUND: The Carotid Revascularization Endarterectomy versus Stenting Trial
      (CREST) received five years' funding ($21 112 866) from the National Institutes
      of Health to compare carotid stenting to surgery for stroke prevention in 2500
      randomized participants at 40 sites. AIMS: Herein we evaluate the change in the
      CREST budget from a fixed to variable-cost model and recommend strategies for the
      financial management of large-scale clinical trials. METHODS: Projections of the
      original grant's fixed-cost model were compared to the actual costs of the
      revised variable-cost model. The original grant's fixed-cost budget included
      salaries, fringe benefits, and other direct and indirect costs. For the variable
      cost model, the costs were actual payments to the clinical sites and core centers
      based upon actual trial enrollment. We compared annual direct and indirect costs
      and per-patient cost for both the fixed and variable models. Differences between
      clinical site and core center expenditures were also calculated. RESULTS: Using a
      variable-cost budget for clinical sites, funding was extended by no-cost
      extension from five to eight years. Randomizing sites tripled from 34 to 109. Of
      the 2500 targeted sample size, 138 (5.5%) were randomized during the first five
      years and 1387 (55.5%) during the no-cost extension. The actual per-patient costs
      of the variable model were 9% ($13 845) of the projected per-patient costs ($152
      992) of the fixed model. CONCLUSIONS: Performance-based budgets conserve funding,
      promote compliance, and allow for additional sites at modest additional cost.
      Costs of large-scale clinical trials can thus be reduced through effective
      management without compromising scientific integrity.

PMID- 24661750
TI  - Adiponectin and waist circumference as predictors of insulin-resistance in women.
AB  - BACKGROUND AND AIMS: The initial disturbance of insulin resistance seems to focus
      on adipose tissue is a dynamic organ involved in many physiological and metabolic
      processes. Expresses and secretes a variety of active peptides, adipocytokines.
      To evaluate the prevalence of insulin-resistance in an healthy urban middle age
      population and to explore the role of adiponectin, inflammatory biomarkers (hs
      CRP) and traditional cardiovascular risk factors as predictors of the insulin
      resistance state. MATERIALS AND METHODS: We studied of 176 participants (117
      women and 59 men, 25-74 years), individuals with diabetes, hypothyroidism or
      hyperthyroidism, infectious disease, renal, or hepatic neoplasms and pregnant
      women were excluded. We evaluated glucose, insulin, adiponectin and hs-CRP.
      RESULTS: We found that 17.2% of individuals presented insulin-resistance.
      Correlation was found between waist circumference, body mass index, blood
      pressure and HOMA index (p<0.01). Adiponectin was associated with the insulin
      resistance (p<0.001) but not hs-CRP. Adiponectin (beta=0.385, p=0.004) and waist
      circumference (beta=0.116, p=0.02) were predictors of IR only in women, meanwhile
      none of the analyzed biomarkers predicted insulin-resistance in men. Besides,
      postmenopausal women presented higher adiponectin levels than premenopausal 7.63
      (4.46-9.58) vs 5.50 (3.83-7.40) MUg/ml, p=0.01. CONCLUSIONS: Adiponectin and
      waist circumference are important predictors of insulin-resistance even in
      healthy non-diabetic women, they may open a new opportunity to improve current
      risk estimation.

PMID- 24661751
TI  - Determination of most suitable cut off point of waist circumference for diagnosis
      of metabolic syndrome in Kerman.
AB  - OBJECTIVES: Metabolic syndrome is a determining indicator of cardiovascular
      diseases and diabetes. Abdominal obesity, determined by measuring waist
      circumference, is one of the most important criteria for diagnosing this
      syndrome. This criterion varies between men and women and among different races.
      The present study aims at the assessment of the sensitivity and specificity of
      the commonly used cut off point of waist circumference, and the estimation of the
      most suitable cut off point of waist circumference for the diagnosis of metabolic
      syndrome in the urban society of Kerman. METHODS: 5332 subjects consisting of
      2966 women and 2366 men, 20 years old and above were studied in a population
      based, cross sectional study. Waist circumference, blood pressure, blood sugar,
      and blood lipids were measured. People with at least two of the NCEP ATP III
      criteria - high blood pressure (BP>130/80), high triglycerides (TG>150), high
      glucose (FBG>100) and low HDL (HDL<40 in men and <50 in women) - were taken as
      population at risk. ROC analysis was used for determining the most suitable cut
      off point of waist circumference. The prevalence of metabolic syndrome was then
      assessed based on IDF, NCEP criteria and the proposed criterion, and agreement
      among the three methods in diagnosing people suffering from metabolic syndrome
      was examined. RESULTS: The average+/-standard deviation of waist circumference in
      women and in men was 83.90+/-12.55 and 87.99+/-11.94 cm respectively. The most
      suitable cut off point of waist circumference for metabolic syndrome diagnosis
      was 86 in women and 89 in men. These circumferences had the highest specificity
      and sensitivity. The prevalence of metabolic syndrome in IDF, NCPE, and the
      proposed criterion was 30.4%, 27.7%, and 35.2% respectively. The new criterion
      and the NCEP criterion achieved the highest agreement (kappa factor=83%).
      CONCLUSION: The cuts off point of waist circumference in men and women are close.
      It is possible, then, to determine a common cut off point of waist circumference
      for both in Iran. Therefore, the cut point of 90-cm of waist circumference
      proposed by the National Obesity Committee seems to be appropriate for the
      Iranian society. These clinical findings should nevertheless be verified by
      simulation.

PMID- 24661752
TI  - Red blood cell distribution width and diabetes-associated complications.
AB  - AIM: Red blood cell distribution width (RDW) is a marker of cardiovascular
      morbidity and mortality. However, there is little data on the relationship
      between RDW and diabetes-associated complications. The aim was to investigate
      whether there is any association between RDW, nephropathy, neuropathy and
      peripheral arterial disease (PAD) in a type 2 diabetic population. METHODS: This
      study included 196 diabetic patients with proliferative diabetic retinopathy. All
      subjects were investigated for diabetic nephropathy, diabetic neuropathy and PAD.
      Participants underwent 24-h blood pressure monitoring and were analysed for
      markers of the metabolic syndrome, inflammation, and insulin resistance. RESULTS:
      57% of the participants had diabetic nephropathy, 46% had diabetic neuropathy
      while 26% had PAD. No significant association was found between RDW, diabetic
      neuropathy and PAD (p=NS). However, RDW was strongly associated with diabetic
      nephropathy (p=0.006), even following adjustment for potential confounding
      variables. Multivariate logistic regression analysis showed RDW (odds ratio [OR]
      1.64, 95% confidence interval [CI] 1.15-2.35, p=0.006), estimated glomerular
      filtration rate (OR 0.98, 95% CI 0.96-0.99, p<0.001), night-time diastolic blood
      pressure (OR 1.07, 95% CI 1.03-1.11, p=0.001) and erythrocyte sedimentation rate
      (OR 1.03, 95% CI 1.004-1.05, p=0.019) to be independently associated with
      diabetic nephropathy. CONCLUSIONS: This is the first study to report lack of
      association between RDW, neuropathy and PAD in subjects with type 2 diabetes
      mellitus. More importantly, RDW was shown to be significantly associated with
      diabetic nephropathy in a type 2 diabetic population with advanced proliferative
      retinopathy independent of traditional risk factors, including diabetes duration
      and glycaemic control.

PMID- 24661753
TI  - Coronary artery disease screening in type II diabetic patients: prognostic value
      of rest and stress echocardiography.
AB  - AIM: Presence of inducible ischemia in type II diabetic patients is associated
      with an adverse outcome, but less is known about prognostic value of resting wall
      motion abnormalities (WMA). MATERIALS AND METHODS: From October 2006 to May 2008,
      278 patients underwent to CAD screening, according to ADA criteria, by dobutamine
      stress echocardiography (DSE). Between July and September 2009, all patients were
      contacted to verify the occurrence of new cardiac events. RESULTS: Resting-WMA
      were present in 63 patients; 88 subjects showed inducible ischemia. During the
      follow-up, we observed 24 new cardiac events; patients with a good outcome showed
      less frequently resting WMA (19 vs 50%). Inducible ischemia (71% vs 28%; p<0.001)
      and a more extensive area of inducible ischemia, expressed by a higher value of
      peak WMSI (1.63+/-0.45 vs 1.17+/-0.31; p<0.0001), were more frequent in patients
      with adverse outcome. A Cox regression analysis showed that only a higher peak
      WMSI (HR 6.645, 95% CI 2.782-15.874, p<0.0001) was associated with a bad outcome.
      Event-free survival was lower in presence of rest WMA (79% vs 94%, p<0.0001) and
      a higher peak WMSI (66% vs 95%, p<0.0001). CONCLUSIONS: In diabetic patients
      presence of an extensive inducible ischemia was independently associated with a
      worst outcome; resting WMA were associated with reduced event-free survival.

PMID- 24661754
TI  - A two fold risk of metabolic syndrome in a sample of patients with schizophrenia:
      do consanguinity and family history increase risk?
AB  - BACKGROUND: Patients with schizophrenia are at greater risk for metabolic
      syndrome (MetS) and other cardiovascular risk factors. OBJECTIVE: The objective
      of the study was to examine the prevalence of metabolic syndrome (MetS) and its
      criteria among patients with schizophrenia (Sz) according to the revised criteria
      of NCEP ATP III and assess which component contributed to the increased risk of
      the MetS in schizophrenia patients. DESIGN: This was a matched case-control
      study. SETTING: Outpatient clinics of the Psychiatry department and Primary
      Health Care (PHC) Centers of the Supreme Council of Health, State of Qatar.
      SUBJECTS AND METHODS: The study was carried out among patients with schizophrenia
      (SZ) and healthy subjects above 20 years old. The study based on matched by age
      and gender of 233 cases and 466 controls. The survey was conducted from June 2010
      to May 2011. Face to face interviews were conducted using a structured
      questionnaire followed by laboratory tests. Metabolic syndrome was defined using
      the National Cholesterol Education Program - Third Adult Treatment Panel (ATP
      III). RESULTS: The prevalence of metabolic syndrome among schizophrenic patients
      (36.5%) were significantly higher than healthy subjects (18.7%) (p<0.001). The
      prevalence of MetS in schizophrenic subjects was reported to be two times higher
      than in the general population. The MetS components were higher among
      schizophrenic patients than healthy subjects. Among the components of MetS,
      central obesity (63.9%) was the most common criteria among patients compared to
      healthy subjects (45.7%) (p<0.001). Schizophrenic patients (27%) were
      significantly obese than the healthy subjects (13.1%). Female schizophrenia
      patients were more likely to have three or more metabolic abnormalities compared
      to men. CONCLUSION: The study indicated that metabolic syndrome was highly
      prevalent in patients with schizophrenia. The female gender was significantly
      associated with a higher prevalence of metabolic syndrome. The identification and
      clinical management of this high risk group is of great importance.

PMID- 24661755
TI  - History of distal gastrectomy prevents metabolic syndrome and chronic kidney
      disease.
AB  - AIMS: Chronic kidney disease (CKD) due to metabolic syndrome has recently become
      a social problem in Japan. In this report, the associations between the history
      of distal gastrectomy (DG) and the incidence of metabolic syndrome or CKD were
      evaluated. METHODS: Arteriosclerosis-related factors were compared among patients
      with a history of DG who were <70 years old (n=41) and controls selected at
      random (n=410) after matching for age and sex. RESULTS: The patients with a
      history of DG were less obese than controls and had lower low-density lipoprotein
      cholesterol and higher high-density lipoprotein cholesterol serum levels.
      Furthermore, they had an excellent estimated glomerular filtration rate, which
      was used as an index of CKD. CONCLUSIONS: These findings suggest that a history
      of DG prevents metabolic syndrome and reduces the risk of CKD.

PMID- 24661756
TI  - Plasma cystatin-C and risk of developing gestational diabetes mellitus.
AB  - AIMS: Cystatin-C, a low molecular weight protein, is effectively applied to
      evaluate the risk of developing renal insufficiency, cardiovascular disorders,
      neural defects, and inflammatory states. However, the role of this biomarker to
      monitor different pregnancy-related complications remains controversial.
      MATERIALS AND METHODS: In the present study, we compared serum cystatin-C
      concentration between pregnant women with gestational diabetes mellitus (GDM) and
      healthy pregnant women to assess value of this biomarker to predict presence of
      GDM in these women. The study consisted of 60 consecutive pregnant women (30
      women suffered GDM and 30 healthy pregnant women) enrolled in Afzalipour hospital
      in Kerman, Iran in 2012. Fasting blood sample was collected to perform
      measurements on plasma glucose, lipids, serum creatinine, and C-cystatin. Serum
      cystatin-C level was quantified using ELISA techniques. RESULTS: Unadjusted
      comparison of cystatin-C level between the two study group showed no significant
      discrepancy between them so that the level of this biomarker in GDM group was
      593.00+/-204.81 mg/L and in healthy group was 531.67+/-87.52 mg/L (P=0.137);
      while in multivariable linear model with the presence of associated variables,
      GDM was a main determinant for increased level of cystatin-C (standardized beta
      of 0.355, P-value of 0.014). CONCLUSION: Gestational age was also identified to
      be another indicator of elevated cystatin-C. In final, our study showed that
      cystatin-C can be a reliable, useful and promising marker of GDM appearance in
      pregnant women.

PMID- 24661757
TI  - Novel sexual dimorphisms of sleep apnea syndrome in diabetes.
AB  - BACKGROUND: OSAS, a frequently neglected, yet frequent comorbidity in T2DM, is
      associated with obesity, metabolic syndrome and central fat. OSAS is better
      documented in males, and this study explored novel gender dimorphisms in T2DM.
      METHODS: Cross-sectional study: 815 T2DM (541 males; 274 females) classified into
      OSAS[-] and OSAS[+] were assessed for cardiometabolic risk factors, glucose
      homeostasis, micro/macroangiopathies, CV risk, autoimmune thyroid disease (AITD);
      and GAD65 antibodies. RESULTS: There was a gender dimorphism in glucose control
      (worse in females), apolipoprotein B100 (higher in females), with apoB100/apoA1
      and log(TG)/HDL-C sexually dimorphic. There was also a marked gender dimorphism
      in GAD65 positivity, higher (+793%) in OSAS[+] females vs. males. There were
      clear sexual dimorphisms in macro-/microangioathies, regarding stroke,
      retinopathy and polyneuropathy. OSAS was not sexually dimorphic regarding age;
      education; and diabetes duration. There was a significant dimorphism in
      ethnicity. There were no gender-specific dimorphisms related to OSAS in
      anthropometrics, nor in hypertension, insulin sensitivity, or hyperbolic product
      loss rate. CONCLUSION: We report a series of novel OSAS-related sexual
      dimorphisms, concerning GAD65 auto-antibodies; polyneuropathy; atherogenic
      dyslipidemia [all increased in females]; diabetic retinopathy; North-Caucasian
      ethnicity; metabolic control; and TIA/stroke prevalence [all lower in females].
      These findings raise challenging questions regarding the reciprocal
      pathophysiology between obstructive sleep disorders and cardiometabolic risk in
      T2DM.

PMID- 24661758
TI  - Novel mutation c.597_598dup in exon 5 of ABCC8 gene causing congenital
      hyperinsulinism.
AB  - Congenital hyperinsulinism (CHI), a clinically and genetically heterogeneous
      disease, characterized by the unregulated secretion of insulin from pancreatic
      beta-cells, is the most common cause of persistent hypoglycemia in infancy. Early
      diagnosis and maintenance of normoglycaemia are essential to prevent adverse
      neurodevelopmental outcomes. The most common and severe forms of CHI are caused
      by inactivating mutations in ABCC8 and KCNJ11 genes, encoding the two subunits of
      the pancreatic beta-cell ATP sensitive potassium channel (KATP). We report a case
      of neonatal CHI due to a novel homozygous recessive mutation in the ABCC8 gene. 

PMID- 24661759
TI  - Cross sectional study to evaluate the effect of duration of type 2 diabetes
      mellitus on the nerve conduction velocity in diabetic peripheral neuropathy.
AB  - OBJECTIVE: To study the nerve conduction velocity in clinically undetectable and
      detectable peripheral neuropathy in type 2 diabetes mellitus with variable
      duration. MATERIAL AND METHODS: This cross sectional study was conducted in
      diagnosed type 2 diabetes mellitus patients. They were divided in groups: Group I
      (n=37) with clinically detectable diabetic peripheral neuropathy of shorter
      duration and Group II (n=27) with clinically detectable diabetic peripheral
      neuropathy of longer duration. They were compared with T2DM patients (n=22)
      without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom
      score (NSS) and neuropathy disability score (NDS) for signs. Nerve conduction
      velocity was measured in both upper and lower limbs. Median, ulnar, common
      peroneal and posterior tibial nerves were selected for motor nerve conduction
      study and median and sural nerves were selected for sensory nerve conduction
      study. RESULTS: The comparisons were done between nerve conduction velocities of
      motor and sensory nerves in patients of clinically detectable neuropathy and
      patients without neuropathy in type 2 diabetes mellitus population. This study
      showed significant electrophysiological changes with duration of disease. Nerve
      conduction velocities in lower limbs were significantly reduced even in patients
      of shorter duration with normal upper limb nerve conduction velocities.
      CONCLUSION: Diabetic neuropathy symptom score (NSS) and neuropathy disability
      score (NDS) can help in evaluation of diabetic sensorimotor polyneuropathy though
      nerve conduction study is more powerful test and can help in diagnosing cases of
      neuropathy.

PMID- 24661760
TI  - India suspends pioglitazone: is it justified?
AB  - In the month of June 2013 the Government of India suddenly suspended three drugs
      for use. The suspension of the anti-diabetic agent came as a rude shock to the
      medical community who has been utilizing this insulin sensitizer for more than a
      decade. We took a close look at the controversies surrounding this agent, the
      current state in the global scenario and how India has reacted in this mini
      review. Like most of the drugs utilized in the management of medical disorders
      pioglitazone also has been under the scanner for quite some time. However no
      definitive cause and effect association with any of the adverse events namely
      bladder cancer, anemia, fractures and heart failure was found. The international
      community responded with caution and refrained from banning the drug outright
      except for France. The ban in India in the absence of incriminating data on the
      Indian population seems out of place. 

PMID- 24661761
TI  - An integrated medical treatment for type-2 diabetes.
AB  - This paper tries to emphasize two relevant concepts: the first is that type 2
      diabetes is a chronic diseases characterized by both a dysmetabolism and a
      chronic oxidative stress. A variety of orthodox drugs are somewhat able to
      correct the metabolic alterations, but do not deal with the chronic inflammation.
      Consequently, as the validity of precisely treating blood with therapeutic ozone
      concentrations in restoring a redox homeostasis has been now demonstrated, the
      integration of ozone therapy appears essential for a rational treatment of type 2
      diabetes. Such a combination may be able to reduce the diabetic epidemic. 

PMID- 24661762
TI  - Depression in type 2 diabetes mellitus--a brief review.
AB  - Diabetes mellitus is a chronic disease which has been associated with depression.
      Depression is more common in adults with type 2 diabetes mellitus (T2DM) as
      compared to those without. Both micro- and macro vascular diabetic complications
      are associated with depression and have shown to increase the risk of mood
      disorder. Further, poor glycemic control in T2DM patients could lead to more
      complications of diabetes and such patients are more likely to develop
      depression. More research is needed in this area to determine the exact
      relationship between depression and T2DM and to unfold the mystery of mechanism
      behind this. 

PMID- 24661763
TI  - Hardiness as a mediator between perceived stress and happiness in nurses.
AB  - ACCESSIBLE SUMMARY: The relevance of the study of happiness and stress in nurses
      has been emphasized. In this sense, the intelligent use of hardiness is enable
      nurses to cope better with stress and contribute to being happier. This study
      aimed to examine the relationship among hardiness, perceived stress, and
      happiness in nurses. Moreover, we examined the mediator role of hardiness on the
      relationship between perceived stress and happiness in nurses. Our study revealed
      that hardi-attitude nurses evaluate situations as less stressful which results in
      a higher happiness. This study showed hardiness as being a protective factor
      against perceived stress and a facilitating factor for happiness in nurses. The
      findings could be important in training future nurses so that hardiness can be
      imparted, thereby giving them the ability to control their stress. Nursing is a
      stressful occupation with high levels of stress within the health professions.
      Given that hardiness is an important construct to enable nurses to cope better
      with stress and contribute to being happier; therefore, it is necessary we
      advance our knowledge about the aetiology of happiness, especially the role of
      hardiness in decreasing stress levels and increasing happiness. The present study
      sought to investigate the role of hardiness as a mediator between perceived
      stress and happiness. The participants, comprising 252 nurses from six private
      hospitals in Tehran, completed the Personal Views Survey, the Perceived Stress
      Scale, and the Oxford Happiness Inventory. Structural Equation Modelling (SEM)
      was used to analyse the data and answer the research hypotheses. As expected,
      hardiness partially mediated between perceived stress and happiness among nurses,
      and nurses with low levels of perceived stress were more likely to report greater
      hardiness and happiness. In addition, nurses with high levels of hardiness were
      more likely to report happiness. This study showed hardiness as being a
      protective factor against perceived stress and a facilitating factor for
      happiness in nurses. The findings could be important in training future nurses so
      that hardiness can be imparted, thereby giving them the ability to control their
      stress.

PMID- 24661764
TI  - Appropriate statistical descriptions for evaluating the predictive role of
      epithelial-to-mesenchymal transition in patients with pancreatic cancer.

PMID- 24661765
TI  - When to perform a pancreatoduodenectomy in the absence of positive histology? A
      consensus statement by the International Study Group of Pancreatic Surgery.
AB  - BACKGROUND: Pancreatoduodenectomy (PD) provides the best chance for cure in the
      treatment of patients with localized pancreatic head cancer. In patients with a
      suspected, clinically resectable pancreatic head malignancy, the need for
      histologic confirmation before proceeding with PD has not historically been
      required, but remains controversial. METHODS: An international panel of
      pancreatic surgeons working in well-known, high-volume centers reviewed the
      literature and worked together to establish a consensus on when to perform a PD
      in the absence of positive histology. RESULTS: The incidence of benign disease
      after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic
      cholangiopancreatography brushings and percutaneous fine-needle aspiration are
      highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic
      ultrasonography (EUS) has greater sensitivity, but it is highly operator
      dependent and increases expense. The incidence of autoimmune pancreatitis (AIP)
      in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum
      levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other
      organ involvement, and Response to therapy) are used for diagnosis. If AIP is
      suspected but not confirmed, the response to a short course of steroids is
      helpful for diagnosis. CONCLUSION: In the presence of a solid mass suspicious for
      malignancy, consensus was reached that biopsy proof is not required before
      proceeding with resection. Confirmation of malignancy, however, is mandatory for
      patients with borderline resectable disease to be treated with neoadjuvant
      therapy before exploration for resection. When a diagnosis of AIP is highly
      suspected, a biopsy is recommended, and a short course of steroid treatment
      should be considered if the biopsy does not reveal features suspicious for
      malignancy.

PMID- 24661766
TI  - Salvage hepatectomy for hilar cholangiocarcinoma with previous biliary metallic
      stent is a matter of specialized hepatobiliary centers.

PMID- 24661767
TI  - Surgical skills needed for humanitarian missions in resource-limited settings:
      common operative procedures performed at Medecins Sans Frontieres facilities.
AB  - BACKGROUND: Surgeons in high-income countries increasingly are expressing
      interest in global surgery and participating in humanitarian missions. Knowledge
      of the surgical skills required to adequately respond to humanitarian emergencies
      is essential to prepare such surgeons and plan for interventions. METHODS: A
      retrospective review of all surgical procedures performed at Medecins Sans
      Frontieres Brussels facilities from June 2008 to December 2012 was performed.
      Individual data points included country of project; patient age and sex; and
      surgical indication and surgical procedure. RESULTS: Between June 2008 and
      December 2012, a total of 93,385 procedures were performed on 83,911 patients in
      21 different countries. The most common surgical indication was for fetal
      maternal pathologies, accounting for 25,548 of 65,373 (39.1%) of all cases. The
      most common procedure was a Cesarean delivery, accounting for a total of 24,182
      or 25.9% of all procedures. Herniorrhaphies (9,873/93,385, 10.6%) and minor
      surgeries (11,332/93,385, 12.1%), including wound debridement, abscess drainage
      and circumcision, were also common. CONCLUSION: A basic skill set that includes
      the ability to provide surgical care for a wide variety of surgical morbidities
      is urgently needed to cope with the surgical need of humanitarian emergencies.
      This review of Medecins Sans Frontieres's operative procedures provides valuable
      insight into the types of operations with which an aspiring volunteer surgeon
      should be familiar.

PMID- 24661768
TI  - The timing of complications impacts risk of readmission after
      hepatopancreatobiliary surgery.
AB  - BACKGROUND: Readmission is frequent in hepatopancreatobiliary (HPB) surgery.
      Medicare began penalizing hospitals recently for excess readmission for specific
      diagnoses, including some operative procedures. We sought to define the incidence
      and risk factors for readmission after HPB surgery. STUDY DESIGN: Elective HPB
      resections were selected from the 2011 American College of Surgeons National
      Surgical Quality Improvement Program (NSQIP) dataset. Risk factors associated
      with readmission were assessed using modified Poisson univariate and adjusted
      regression models. RESULTS: We identified 5,081 patients; 2,980 underwent
      pancreatic resection and 2,101 had a hepatectomy. Median age was 62
      (interquartile range, 52-70), 53% of patients were women; 74% were non-Hispanic
      white; and 31% were American Society of Anesthesiologists (ASA) class 2, and 64%
      were ASA class 3. About 75% of cases had a malignant diagnosis on final
      pathology. Of all these patients, 16.2% were readmitted within 30 days of
      operation. The strongest risk factors for readmission on multivariable analysis
      were minor (risk ratio [RR], 3.13, 95% confidence interval [CI], 2.47-3.97; P <
      .001) and major (RR, 8.45; 95% CI, 7.59-9.40; P < .001) complications after
      discharge; in contrast, major inpatient complications only had a modest effect on
      the risk of readmission (RR, 1.29; 95% CI, 1.05-1.58; P < .014). Among all
      patients who were readmitted, 40% experienced a major complication after
      discharge, and 83% of patients who had a major outpatient complication were
      readmitted. CONCLUSION: Outpatient complications were by far the strongest risk
      factor for readmission. Decreasing complications as well as improving outpatient
      case management to prevent and treat postdischarge complications hold
      considerable promise in the efforts to decrease readmission.

PMID- 24661769
TI  - Editor's note.

PMID- 24661770
TI  - Management of primary metastatic breast cancer in elderly patients--an
      international comparison of oncogeriatric versus standard care.
AB  - BACKGROUND: An oncogeriatric approach may affect management of elderly patients
      with breast cancer. However, little is known about oncogeriatric care in the
      metastatic setting. Therefore, we performed an international comparison of
      management of elderly patients with primary metastatic disease who were treated
      in two different care settings. MATERIALS AND METHODS: Patients who were
      >=70years at diagnosis of primary metastatic disease were eligible. The first
      cohort comprised a population-based cohort of 104 patients (Comprehensive Cancer
      Center West, The Netherlands), who all received standard care. The second cohort
      comprised a hospital-based cohort of 42 patients (H. Lee Moffitt Cancer Center,
      Florida, United States), who all received oncogeriatric care. RESULTS: No large
      differences in patient and tumor characteristics were observed between both
      cohorts. Most patients in the standard care cohort received systemic therapy as
      primary therapy, whereas most patients in the oncogeriatric cohort received a
      combination of systemic and local therapy. Patients in the standard care cohort
      received fewer lines of treatment (mean number of treatments 2.1 vs. 3.6,
      p<0.001), and particularly received less breast surgery, chemotherapy, and
      trastuzumab. Three-year overall mortality was 71% (95% CI: 61-83%) as compared to
      58% (95% CI: 42-75%) among patients in the oncogeriatric care cohort
      (multivariable HR: 1.59 [95% CI: 0.88-2.87], p=0.125). CONCLUSIONS: In primary
      metastatic breast cancer, oncogeriatric care intensifies treatment and might
      improve survival in elderly patients. Future studies on a larger scale should
      investigate the potential for improved survival, and whether this is accompanied
      by a better (preservation of) quality of life and functional status.

PMID- 24661771
TI  - Has breast cancer in the elderly remained the same over recent decades? A
      comparison of two groups of patients 70years or older treated for breast cancer
      twenty years apart.
AB  - OBJECTIVES: Breast cancer (BC) in the elderly population is by far the most
      frequent malignancy in Western countries; however, little evidence is available
      regarding the specific management of this group. The purpose of this study was to
      identify how the biological and clinical characteristics of cancer have changed
      over the past 20years by comparing two groups of elderly patients with breast
      cancer operated on 20years apart. The secondary endpoint was to underline
      potential changes in surgical strategy over the past 20years. MATERIALS AND
      METHODS: One group of consecutive elderly patients undergoing surgery for BC
      between January 1990 and December 1993 (Group A), and one group undergoing
      surgery between January 2008 and December 2011 (Group B) were identified and
      analyzed. Data regarding surgical treatment, stage, tumor grading, hormonal and
      HER2/neu receptors, and Ki-67 were collected and compared. RESULTS: A total of
      422 elderly patients underwent surgical treatment, 142 in Group A and 280 in
      Group B. An earlier stage at presentation was detected in Group B, T1 (57.5% B
      vs. 31.6% A) and N0 (64.6% B vs. 54.2% A). Surgical treatment in the first group
      was more extensive while conservative procedures were more frequently performed
      in the second group. Despite the earlier presentation, tumor grade was higher in
      Group B (G3 10.6% A vs. 32.1% B, p<0.05). Overexpression of Ki-67 was again more
      frequent in Group B (56.2% B vs. 32.5% A, p<0.05). Hormonal and HER2/neu receptor
      expression was comparable. CONCLUSIONS: Nowadays, elderly patients with BC are
      more likely to present at an early stage; therefore, conservative surgery is a
      feasible option. Despite potential bias related to changes of pathology and
      immunohistochemistry examination techniques over the decades, the biological
      characteristics of recent patients with BC seem to be consistent with more
      aggressive tumors. Tailored treatment should be offered with regard to biological
      age, the cancer-specific profile and active life expectancy.

PMID- 24661772
TI  - [Birdshot chorioretinopathy].

PMID- 24661773
TI  - Predictive value of high-sensitivity troponin-I for future adverse cardiovascular
      outcome in stable patients with type 2 diabetes mellitus.
AB  - INTRODUCTION: High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT)
      are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of
      the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have
      yielded conflicting results. This study aimed to determine whether hs-TnI, which
      is detectable in a higher proportion of normal subjects than hsTnT, is associated
      with a major adverse cardiovascular event(MACE) in T2DM patients. METHODS AND
      RESULTS: We compared hs-TnI level in stored serum samples from 276 consecutive
      patients (mean age 65 +/- 10 years; 57% male) with T2DM with that of 115 age-and
      sex-matched controls. All T2DM patients were prospectively followed up for at
      least 4 years for incidence of MACE including heart failure(HF), myocardial
      infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with
      T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L,
      female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43
      MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14).
      Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE,
      HF, MI and cardiovascular mortality. Although multivariate analysis revealed that
      an elevated hs-TnI independently predicted MACE, it had limited
      sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a
      normal hs-TnI level had an excellent negative predictive value(92.2%) for future
      MACE in patients with T2DM. CONCLUSION: The present study demonstrates that
      elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI
      and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent
      negative predictive value for future adverse cardiovascular events during long
      term follow-up.

PMID- 24661774
TI  - Interval type-2 fuzzy PID controller for uncertain nonlinear inverted pendulum
      system.
AB  - In this paper, the interval type-2 fuzzy proportional-integral-derivative
      controller (IT2F-PID) is proposed for controlling an inverted pendulum on a cart
      system with an uncertain model. The proposed controller is designed using a new
      method of type-reduction that we have proposed, which is called the simplified
      type-reduction method. The proposed IT2F-PID controller is able to handle the
      effect of structure uncertainties due to the structure of the interval type-2
      fuzzy logic system (IT2-FLS). The results of the proposed IT2F-PID controller
      using a new method of type-reduction are compared with the other proposed IT2F
      PID controller using the uncertainty bound method and the type-1 fuzzy PID
      controller (T1F-PID). The simulation and practical results show that the
      performance of the proposed controller is significantly improved compared with
      the T1F-PID controller. 

PMID- 24661775
TI  - Effects of extracellular DNA from Candida albicans and pneumonia-related
      pathogens on Candida biofilm formation and hyphal transformation.
AB  - AIMS: The aim of this study was to investigate the effects of genomic DNA
      purified from Candida albicans and pneumonia-related pathogens, Pseudomonas
      aeruginosa and Staphylococcus aureus, on in vitro biofilm formation and
      morphological change of 3 Candida species (C. albicans, C. glabrata, and C.
      tropicalis). METHODS AND RESULTS: Biofilm formation was evaluated by the crystal
      violet assay and colony-forming unit counts. Morphological characteristics of
      biofilms were evaluated by scanning electron microscopy and fluorescence
      microscopy. Addition of DNA at a low concentration (<1.0 MUg ml(-1))
      significantly increased biofilm mass of all three Candida species. In contrast,
      the addition of DNA at a high concentration (10 MUg ml(-1)) decreased the biofilm
      mass. Interestingly, the formation of hyphae in a dense network of yeast cells
      was observed in C. albicans biofilms exposed to a low concentration of DNA (<1.0
      MUg ml(-1)). CONCLUSIONS: These findings demonstrated that extracellular DNA
      (eDNA) plays a crucial role in Candida biofilm formation and suggested that eDNA
      may induce the morphological transition from yeast to hyphal growth form during
      C. albicans biofilm development. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel
      therapy targeting eDNA may be applicable for Candida infection to decrease
      biofilm formation and hyphal formation.

PMID- 24661776
TI  - Zoonotic helminths of urban brown rats (Rattus norvegicus) in the UK: neglected
      public health considerations?
AB  - Urban brown rats (Rattus norvegicus) carry microbial human pathogens but their
      role as reservoir hosts for helminths of public health importance is less well
      known. In this study, 42 brown rats trapped on Merseyside were subject to
      thorough combined helminthological and pathohistological post-mortem examination.
      Eggs of the rodent-borne zoonotic nematode Calodium hepaticum were initially
      detected in histological sections of the livers of 9.5% of rats, but overall
      diagnostic sensitivity increased to 16.6% when entire liver tissue was disrupted
      and the resulting filtrates were examined for released eggs. In their rat host,
      mainly trapped inside the dockland, infections with C. hepaticum were associated
      with a chronic multifocal pyogranulomatous hepatitis with intralesional eggs and
      peripheral fibrosis. Mean intensity of hepatic C. hepaticum egg infections was
      1041 eggs. This is the first report of C. hepaticum in an urban brown rat
      population in the UK and provides original data for liver egg burdens in this
      abundant commensal rodent. The zoonotic cestode Rodentolepis nana had a
      prevalence of infection of 14.3%. Rodent-specific, non-zoonotic helminths found
      were the spiruroid Mastophorus muris (16.0%) in the stomach, the trichuroid
      Trichosomoides crassicauda in the urinary bladder (31.0%); the ascarid Heterakis
      spumosa was the commonest helminth of the large intestine (76.2%). Many millions
      of brown rats inhabit cities and rural areas of the UK, and the infective stages
      of the zoonotic worm species, particularly C. hepaticum, are likely to be widely
      distributed in the environment presenting a threat to public health. 

PMID- 24661778
TI  - A comprehensive dosimetric study of pancreatic cancer treatment using three
      dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation
      therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive
      scattering and modulated-scanning proton therapy (PT).
AB  - With traditional photon therapy to treat large postoperative pancreatic target
      volume, it often leads to poor tolerance of the therapy delivered and may
      contribute to interrupted treatment course. This study was performed to evaluate
      the potential advantage of using passive-scattering (PS) and modulated-scanning
      (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative
      pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic
      cancer who had been previously treated with PS PT in University of Pennsylvania
      Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical
      target volume (CTV) includes the pancreatic tumor bed as well as the adjacent
      high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D)
      computed tomography (CT), taking into account target motion from breathing cycle.
      Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity
      modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2
      field PS and MS PT were created on the patients' average CT. All the plans
      delivered 50.4Gy to the planning target volume (PTV). Overall, 98% of PTV was
      covered by 95% of the prescription dose and 99% of iCTV received 98% prescription
      dose. The results show that all the proton plans offer significant lower doses to
      the left kidney (mean and V18Gy), stomach (mean and V20Gy), and cord (maximum
      dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum
      dose. In addition, MS PT also provides lower doses to the right kidney (mean and
      V18Gy), liver (mean dose), total bowel (V20Gy and mean dose), and small bowel
      (V15Gy absolute volume ratio) compared with all the photon plans and PS PT. The
      dosimetric advantage of PT points to the possibility of treating tumor bed and
      comprehensive nodal areas while providing a more tolerable treatment course that
      could be used for dose escalation and combining with radiosensitizing
      chemotherapy. 

PMID- 24661777
TI  - Reprogramming antitumor immunity.
AB  - Regenerative medicine holds great promise in replacing tissues and organs lost to
      degenerative disease and injury. Application of the principles of cellular
      reprogramming for the treatment of cancer, however, is not well established.
      Here, we present an overview of cellular reprogramming techniques used in
      regenerative medicine, and within this context, envision how the scope of
      regenerative medicine may be expanded to treat metastatic cancer by revitalizing
      an exhausted and senescent immune system. 

PMID- 24661779
TI  - Acute heart failure as a form of relapse in a patient with adult-onset Still
      disease.

PMID- 24661780
TI  - Use and effectiveness of prothrombin complex concentrates vs fresh frozen plasma
      in gastrointestinal hemorrhage due to warfarin usage in the ED.
AB  - OBJECTIVES: High International Normalized Ratio (INR) level resulting from
      warfarin use increases the risk of gastrointestinal hemorrhages. We aimed to
      compare the efficacy of prothrombin complex concentrates (PCC) and fresh frozen
      plasma (FFP) at lowering the INR level, decreasing active hemorrhages visible by
      endoscopy, and shortening the length of stay at the emergency department (ED).
      METHOD: This study is a prospective cohort study of consecutive patents with
      gastrointestinal hemorrhages that received either PCC or FFP. With strict
      exclusion criteria, only patients over 18 years of age with a high INR level
      (>2.1) due to warfarin usage were included. RESULTS: A total of 40 patients (18
      female) were included in the study, 20 each in the PCC and FFP groups. For the
      PCC group, the mean INR levels at the second and sixth hours were lower than
      those for the FFP group (second hour INR: 1.53 vs 4.50, P<.01, sixth hour INR:
      1.52 vs 2.41, P<.01). Seven patients experienced active bleeding (Forrest 1) in
      the FFP group, whereas no patient experienced active bleeding in the PCC group
      based on the Forrest classification (35% vs 0%, P<.01), and only 3 patients in
      the FFP group underwent invasive/surgical treatment (15% vs 0%, P<.01). The ED
      length of stay was lower for the PCC group (1.62 days vs 3.46 days, P<.01).
      CONCLUSION: For patients experiencing a gastrointestinal hemorrhage, INR levels
      were reversed more quickly, there was less active bleeding on endoscopy, and the
      ED length of stay was lower in the PCC group than in the FFP group.

PMID- 24661781
TI  - Compression-only cardiopulmonary resuscitation vs standard cardiopulmonary
      resuscitation: an updated meta-analysis of observational studies.
AB  - OBJECTIVES: To perform an updated meta-analysis of observational studies with
      unstratified cohort addressing whether compression-only cardiopulmonary
      resuscitation (CPR), compared with standard CPR, improves outcomes in adult
      patients with out-of-hospital cardiac arrest and a subgroup meta-analysis for the
      patients with cardiac etiology arrest. METHODS: We searched the relevant
      literature from MEDLINE and EMBASE databases. The baseline information and
      outcome data (survival to hospital discharge, favorable neurologic outcome at
      hospital discharge, and return of spontaneous circulation on hospital arrival)
      were extracted both in an out-of-hospital cardiac arrest and cardiac origin
      arrest subgroup. Meta-analyses were performed by using Review Manager 5.0.
      RESULTS: Eight studies involving 92,033 patients were eligible. Overall meta
      analysis showed that standard CPR was associated with statistically improved
      survival to hospital discharge (risk ratio [RR], 0.95 [95% confidence interval,
      0.91-0.99]) and return of spontaneous circulation on hospital arrival (RR, 0.95
      [95% confidence interval, 0.92-0.99]) compared with compression-only CPR, but
      there is no significant difference in favorable neurologic outcome at hospital
      discharge between 2 CPR methods (RR, 0.97 [95% confidence interval, 0.91-1.04]).
      In the subgroup of patients with a cardiac cause of arrest, the pooled meta
      analysis found compression-only CPR resulted in the similar survival to hospital
      discharge as standard CPR (RR, 0.99 [95% confidence interval, 0.94-1.05]).
      CONCLUSIONS: This meta-analysis found that compression-only CPR resulted in the
      similar survival rate as the standard CPR in the cardiac etiology subgroup. It is
      unclear for the patients with noncardiac cause of arrest and with long periods of
      untreated arrest.

PMID- 24661782
TI  - Overproduction of Toxoplasma gondii cyclophilin-18 regulates host cell migration
      and enhances parasite dissemination in a CCR5-independent manner.
AB  - BACKGROUND: Toxoplasma gondii hijacks host cells to allow it to disseminate
      throughout a host animal; however, the migratory machinery involved in this
      process has not been well characterized. We examined the functional role of T.
      gondii cyclophilin 18 (TgCyp18) in host cell recruitment using recombinant
      parasites transfected with TgCyp18. RESULTS: High levels of TgCyp18 enhanced IL
      12 production in cysteine-cysteine chemokine receptor 5 (CCR5) knockout mice
      (CCR5-/-) that had been infected peritoneally with T. gondii. Recruitment of
      CD11b+ cells to the infection site was enhanced in a CCR5-independent manner. T.
      gondii spread to several organs, particularly the liver, in a TgCyp18-dependent
      and CCR5-independent manner. Additionally, CCL5 levels were upregulated in
      macrophages treated with recombinant protein TgCyp18 and in the peritoneal fluids
      of the infected CCR5-/- mice. Furthermore, the chemokines involved in macrophage
      migration, CCL2 and CXCL10, were upregulated in the livers of CCR5-/- mice
      infected with recombinant parasites that had been transfected with TgCyp18.
      CONCLUSION: TgCyp18 may play a crucial role in macrophage migration, and in
      assisting with transport of T. gondii via CCR5-independent mechanisms. TgCyp18
      may also play a role with CCL5 in the migration of macrophages to the site of
      infection, and with CCL2 and CXCL10 in the transport of T. gondii-infected cells
      to the liver.

PMID- 24661783
TI  - Utilization and adherence patterns of subcutaneously administered anti-tumor
      necrosis factor treatment among rheumatoid arthritis patients.
AB  - BACKGROUND: Adherence to therapy is a key requirement underlying achievement of
      clinical outcomes in randomized controlled drug registration trials. In
      postmarketing studies, comparison of adherence among therapies can become more
      complicated when drug dosing and administration schedules differ or when methods
      used to measure adherence are not consistently applied. OBJECTIVE: The objective
      of this exploratory study was to investigate a broad range of utilization and
      adherence outcomes associated with subcutaneous biologic treatments for
      rheumatoid arthritis (RA). METHODS: Adult patients (aged >=18 years) exhibiting
      >=2 claims with an RA diagnosis (code 714.x), at least 24 months of continuous
      medical and pharmacy eligibility, and 30-day supplies of adalimumab, etanercept,
      or golimumab were selected from the Optum Insight Clinformatics database.
      Adherence and utilization measures were calculated and compared across treatment
      groups. RESULTS: A total of 1532 adalimumab, 2099 etanercept, and 261 golimumab
      patients met inclusion criteria. Compared with both adalimumab and etanercept
      patients, golimumab patients were significantly more likely to have a medication
      possession ratio of >=0.80 (82% vs 71% vs 62%; P < 0.001) and significantly less
      likely to have >=4 late medication refills (6.9% vs 17.7% vs 26.1%; P < 0.001 for
      all). Etanercept patients had significantly greater refill intervals (37.7 vs
      34.9 and 35.1 days) and had the lowest proportion of adherent fills (70% vs 77%
      and 75%) compared with both golimumab and adalimumab patients (P < 0.001 for
      all). Bivariate effects were reproduced in multivariate models that controlled
      for treatment duration. CONCLUSIONS: A number of statistically significant
      medication adherence differences were observed among golimumab, adalimumab, and
      etanercept patients in treatment for RA. Overall, golimumab patients appeared to
      be the most adherent group. Findings may be partially attributable to golimumab
      patients' likely increased disease severity, their prior experience with biologic
      medication, or golimumab's once-monthly dosing schedule, which requires fewer
      administrations than both adalimumab and etanercept.

PMID- 24661784
TI  - The effect of weight on the efficacy and safety of C1 esterase inhibitor
      concentrate for the treatment of acute hereditary angioedema.
AB  - BACKGROUND: Despite the worldwide obesity epidemic, there have been very few
      studies investigating the influence of body weight on treatment dosing and
      outcomes in patients with hereditary angioedema (HAE). OBJECTIVE: The purpose of
      this analysis was to determine whether the standard weight-based dosing
      recommendation of C1 esterase inhibitor (C1-INH) concentrate (20 IU/kg) is
      adequate in HAE patients with a high body mass index (BMI). METHODS: Data from
      patients treated for HAE attacks with 20 IU/kg of C1-INH concentrate were
      retrospectively analyzed from the open-label IMPACT2 study (International
      Multicenter Prospective Angioedema C1-INH Trial). Patients were categorized
      according to BMI as being normal body weight, overweight, or obese. Efficacy end
      points were time to onset of symptom relief and time to complete resolution of
      symptoms. The safety profile was evaluated according to adverse events occurring
      within 7 to 9 days of treatment. RESULTS: Of 57 patients, 24 (42%) were of normal
      body weight, 20 (35%) were overweight, and 13 (23%) were obese. Median (95% CI)
      time to onset of symptom relief was 0.37 hour (0.29-0.57) in normal-weight
      patients, 0.48 hour (0.39-0.53) in overweight patients, and 0.58 hour (0.41-0.94)
      in obese patients. Median time (95% CI) to complete resolution of symptoms was
      15.2 hours (9.3-23.2) in normal-weight patients, 22.6 hours (11.3-44.6) in
      overweight patients, and 11.0 hours (5.6-23.6) in obese patients (differences not
      significant). There were no relevant differences in the incidence of adverse
      events in normal-weight patients (54%), overweight patients (30%), and obese
      patients (54%). CONCLUSIONS: Treatment of HAE attacks with weight-based doses of
      C1-INH concentrate provided reliable treatment response, regardless of body
      weight, in these patients with HAE.

PMID- 24661786
TI  - Health literacy: why it matters to South Asian men with diabetes.
AB  - This study aims to explore the health literacy needs of South Asian men with
      diabetes to generate scoping data to inform culturally appropriate interventions
      with this group. Health literacy levels were measured using the TOFHLA-UK (n=45)
      and supplemented by semi-structured interviews with healthcare providers (n=12).
      Data suggest that the majority of participants from this cohort tend to have
      marginal to inadequate health literacy levels. A generational gap was also found.
      Although language is a common barrier, low literacy confounds this issue since
      some patients are unable to read even in their own language. Thus health
      communication and care plans need to be simplified to match current health
      literacy levels of South Asian men with diabetes. Interventions need to work
      around cultural norms and collaborate with community members. Research and
      interventions that consider the needs of older generations of South Asian people
      with diabetes are also needed. 

PMID- 24661787
TI  - The CHH motif in sugar beet satellite DNA: a modulator for cytosine methylation.
AB  - Methylation of DNA is important for the epigenetic silencing of repetitive DNA in
      plant genomes. Knowledge about the cytosine methylation status of satellite DNAs,
      a major class of repetitive DNA, is scarce. One reason for this is that arrays of
      tandemly arranged sequences are usually collapsed in next-generation sequencing
      assemblies. We applied strategies to overcome this limitation and quantified the
      level of cytosine methylation and its pattern in three satellite families of
      sugar beet (Beta vulgaris) which differ in their abundance, chromosomal
      localization and monomer size. We visualized methylation levels along pachytene
      chromosomes with respect to small satellite loci at maximum resolution using
      chromosome-wide fluorescent in situ hybridization complemented with
      immunostaining and super-resolution microscopy. Only reduced methylation of many
      satellite arrays was obtained. To investigate methylation at the nucleotide level
      we performed bisulfite sequencing of 1569 satellite sequences. We found that the
      level of methylation of cytosine strongly depends on the sequence context:
      cytosines in the CHH motif show lower methylation (44-52%), while CG and CHG
      motifs are more strongly methylated. This affects the overall methylation of
      satellite sequences because CHH occurs frequently while CG and CHG are rare or
      even absent in the satellite arrays investigated. Evidently, CHH is the major
      target for modulation of the cytosine methylation level of adjacent monomers
      within individual arrays and contributes to their epigenetic function. This
      strongly indicates that asymmetric cytosine methylation plays a role in the
      epigenetic modification of satellite repeats in plant genomes. 

PMID- 24661785
TI  - Reliability of causality assessment for drug, herbal and dietary supplement
      hepatotoxicity in the Drug-Induced Liver Injury Network (DILIN).
AB  - BACKGROUND & AIMS: Because of the lack of objective tests to diagnose drug
      induced liver injury (DILI), causality assessment is a matter of debate. Expert
      opinion is often used in research and industry, but its test-retest reliability
      is unknown. To determine the test-retest reliability of the expert opinion
      process used by the Drug-Induced Liver Injury Network (DILIN). METHODS: Three
      DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five
      categories representing levels of likelihood of DILI. Adjudication is based on
      retrospective assessment of gathered case data that include prospective follow-up
      information. One hundred randomly selected DILIN cases were re-assessed using the
      same processes for initial assessment but by three different reviewers in 92% of
      cases. RESULTS: The median time between assessments was 938 days (range 140
      2352). Thirty-one cases involved >1 agent. Weighted kappa statistics for overall
      case and individual agent category agreement were 0.60 (95% CI: 0.50-0.71) and
      0.60 (0.52-0.68) respectively. Overall case adjudications were within one
      category of each other 93% of the time, while 5% differed by two categories and
      2% differed by three categories. Fourteen per cent crossed the 50% threshold of
      likelihood owing to competing diagnoses or atypical timing between drug exposure
      and injury. CONCLUSIONS: The DILIN expert opinion causality assessment method has
      moderate interobserver reliability but very good agreement within one category. A
      small but important proportion of cases could not be reliably diagnosed as >=50%
      likely to be DILI.

PMID- 24661788
TI  - Empathy dolls: are they a source of cross-contamination between patients?
AB  - Following a cluster of two patients with identical strains of Clostridium
      perfringens prosthetic joint infections on an ortho-geriatric ward in a teaching
      hospital in England, investigations were conducted into infection control
      practices. It emerged that empathy dolls were being used to help alleviate
      agitation in dementia patients; this had been introduced without consultation
      with the infection prevention and control team. Environmental testing of the doll
      pre and post laundry at different temperatures helped to establish the types and
      numbers of organisms present. This testing enabled our unit to provide guidance
      on the optimum strategy for decontamination and safe use of these dolls. 

PMID- 24661789
TI  - High-level endoscope disinfection processes in emerging economies: financial
      impact of manual process versus automated endoscope reprocessing.
AB  - BACKGROUND: The use of flexible endoscopes is growing rapidly around the world.
      Dominant approaches to high-level disinfection among resource-constrained
      countries include fully manual cleaning and disinfection and the use of automated
      endoscope reprocessors (AERs). Suboptimal reprocessing at any step can
      potentially lead to contamination, with consequences to patients and healthcare
      systems. AIM: To compare the potential results of guideline-recommended AERs to
      manual disinfection along three dimensions - productivity, need for endoscope
      repair, and infection transmission risk in India, China, and Russia. METHODS:
      Financial modelling using data from peer-reviewed published literature and
      country-specific market research. FINDINGS: In countries where revenue can be
      gained through productivity improvements, conversion to automated reprocessing
      has a positive direct impact on financial performance, paying back the capital
      investment within 14 months in China and seven months in Russia. In India, AER
      generated savings and revenue offset nearly all of the additional operating costs
      needed to support automated reprocessing. CONCLUSION: Among endoscopy facilities
      in India and China, current survey-reported practices in endoscope reprocessing
      using manual soaking may place patients at risk of exposure to pathogens leading
      to infections. Conversion from manual soak to use of AERs, as recommended by the
      World Gastroenterology Organization, may generate cost and revenue offsets that
      could produce direct financial gains for some endoscopy units in Russia and
      China.

PMID- 24661790
TI  - Difficulties with molecular diagnostic tests for mould and yeast infections:
      where do we stand?
AB  - PCR assays have not reached the same level of acceptance for the detection of
      human fungal pathogens as for other micro-organisms, mainly because the low
      number of micro-organisms challenges the detection limits of PCR. Therefore,
      whereas meta-analyses focusing on clinical validation suggest interest in adding
      PCR results to the diagnostic workup for invasive fungal disease (IFD) along with
      clinical evaluation, CT scans, classical mycology and antigen detection, no
      consensual PCR method has emerged. Compared with the end-point format of the
      1990s, real-time quantitative PCR is a major breakthrough. This format prevents
      contamination with previously amplified products, provides the yield of
      amplification, allows for developing consensus procedures and should therefore be
      the only format used. An internal control is now mandatory to avoid false
      negative results. Primer design strongly impacts on the objectives: pan-fungal
      primers can provide false-positive results due to environmental fungal DNA
      contamination; conversely, species-specific primers miss infections caused by
      untargeted fungi. Unresolved issues include the best specimens to be used; serum
      is currently preferred to blood because of the ease of the DNA extraction step.
      Work is in progress to establish standards at least for Aspergillus PCR, and the
      implementation of quality controls should help centres to improve assays.
      Eventually, the classical analysis of biomarker performance does not consider the
      evolving risk factors and changing treatments during IFD, which can lead to
      variable conclusions. New statistical methods such as event history analysis
      should be considered.

PMID- 24661792
TI  - A fatal case of atrioesophageal fistula following radiofrequency ablation of left
      atrium and pulmonary veins for atrial fibrillation.
AB  - Atrial fibrillation (AF) is associated with significant morbidity and mortality.
      Hemodynamic compromise and formation of thrombi within the fibrillating atrium or
      atrial appendage can occur. Surgical treatment aims to eliminate dysrhythmia
      triggering foci in the pulmonary veins and posterior left atrium by
      radiofrequency ablation techniques using ohmic heat. As medical treatment may be
      ineffective, radiofrequency catheter ablation is increasingly being used by
      interventional cardiac electrophysiologists for AF. Serious complications have
      been observed among patients who have undergone radiofrequency ablation,
      atrioesophageal fistula being a very rare example. This case describes a 43-year
      old man who died after the development of an atrioesophageal fistula following
      radiofrequency ablation of the left atrium and pulmonary veins for treatment of
      AF.

PMID- 24661791
TI  - Verbal fluency in essential tremor patients: the effects of deep brain
      stimulation.
AB  - OBJECTIVE: To assess the effects of different frequencies of thalamic Deep-Brain
      Stimulation (DBS) on cognitive performance of patients suffering from Essential
      Tremor (ET). METHODS: In 17 ET-patients with thalamic-DBS, Tremor-Rating-Scale
      (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word
      Test and Digit-span-test were investigated in three randomized stimulation
      settings: i) high-frequency stimulation (HFS), ii) low-frequency stimulation
      (LFS) and iii) OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one
      way repeated measures analysis of variance for cognitive performance were
      calculated. RESULTS: Tremor was reduced during HFS (MeanTRS-HFS = 12.9 +/- 9.6)
      compared to DBS-OFF (MeanTRS-OFF = 44.4 +/- 19.8, P < .001) and to LFS (MeanTRS
      10 Hz = 50.0 +/- 24.2; P < .001). While performance of Stroop-task and digit-span
      remained unaffected by stimulation-settings (P > .05), phonemic and semantic VF
      differed significantly between the three conditions (FPvf = 5.28, FSvf = 3.41,
      both P < .05). Post-hoc comparisons revealed significant differences for both
      phonemic and semantic VF between LFS (MeanPvf-10 Hz = 54.6 +/- 9.2, MeanSvf-10 Hz
      = 56.4 +/- 7.9) and HFS (MeanPvf-ON = 48.3 +/- 11.4, MeanSvf-ON = 51.1 +/- 11.0,
      both P < .05), while DBS-OFF (MeanPvf-OFF = 51.2 +/- 9.3, MeanSvf-OFF = 53.6 +/-
      12.9) and HFS and DBS-OFF and LFS did not differ significantly (P > .05).
      CONCLUSIONS: HFS compared to LFS or DBS-OFF significantly reduced tremor but
      simultaneously worsened VF while working memory and cognitive inhibition remained
      unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data
      emphasize the relevance of thalamocortical loops for verbal fluency but also
      suggest that more sophisticated DBS-regimes in ET may improve both motor and
      cognitive performance.

PMID- 24661793
TI  - Implementing Global Fund programs: a survey of opinions and experiences of the
      Principal Recipients across 69 countries.
AB  - BACKGROUND: Principal Recipients (PRs) receive money from the Global Fund to
      fight AIDS, Tuberculosis and Malaria (Global Fund) to manage and implement
      programs. However, little research has gone into understanding their opinions and
      experiences. This survey set out to describe these, thereby providing a baseline
      against which changes in PR opinions and experiences can be assessed as the
      recently introduced new funding model is rolled out. METHODOLOGY: An internet
      based questionnaire was administered to 315 PRs. A total of 115 responded from 69
      countries in Africa, Asia, Eastern Europe and Latin America. The study was
      conducted between September and December 2012. FINDINGS: Three quarters of PRs
      thought the progress update and disbursement request (PU/DR) system was a useful
      method of reporting grant progress. However, most felt that the grant negotiation
      processes were complicated, and that the grant rating system did not reflect
      performance.While nearly all PRs were happy with the work being done by sub
      Recipients (92%) and Fund Portfolio Managers (86%), fewer were happy with the
      Office of the Inspector General (OIG). Non-government PRs were generally less
      happy with the OIG's work compared to government PRs.Most PRs thought the Global
      Fund's Voluntary Pooled Procurement system made procurement easier. However, only
      29% said the system should be made compulsory.When asked which aspects of the
      Global Fund's operations needed improvement, most PRs said that the Fund should
      re-define and clarify the roles of different actors, minimize staff turnover at
      its Secretariat, and shorten the grant application and approval processes. All
      these are currently being addressed, either directly or indirectly, under a new
      funding model. Vigorous assessments should nonetheless follow the roll-out of the
      new model to ensure the areas that are most likely to affect PR performance
      realize sustained improvement. CONCLUSIONS: Opinions and experiences with the
      Global Fund were varied, with PRs having good communication with Fund Portfolio
      Managers and sub-Recipients, but being unhappy with the grant negotiation and
      grant rating systems. Recommendations included simplifying grant processes,
      finding performance assessment methods that look beyond numbers, and employing
      Local Fund Agents who understand public health aspects of programs.

PMID- 24661794
TI  - Developing a new production host from a blueprint: Bacillus pumilus as an
      industrial enzyme producer.
AB  - BACKGROUND: Since volatile and rising cost factors such as energy, raw materials
      and market competitiveness have a significant impact on the economic efficiency
      of biotechnological bulk productions, industrial processes need to be steadily
      improved and optimized. Thereby the current production hosts can undergo various
      limitations. To overcome those limitations and in addition increase the diversity
      of available production hosts for future applications, we suggest a Production
      Strain Blueprinting (PSB) strategy to develop new production systems in a reduced
      time lapse in contrast to a development from scratch.To demonstrate this
      approach, Bacillus pumilus has been developed as an alternative expression
      platform for the production of alkaline enzymes in reference to the established
      industrial production host Bacillus licheniformis. RESULTS: To develop the
      selected B. pumilus as an alternative production host the suggested PSB strategy
      was applied proceeding in the following steps (dedicated product titers are
      scaled to the protease titer of Henkel's industrial production strain B.
      licheniformis at lab scale): Introduction of a protease production plasmid,
      adaptation of a protease production process (44%), process optimization (92%) and
      expression optimization (114%). To further evaluate the production capability of
      the developed B. pumilus platform, the target protease was substituted by an
      alpha-amylase. The expression performance was tested under the previously
      optimized protease process conditions and under subsequently adapted process
      conditions resulting in a maximum product titer of 65% in reference to B.
      licheniformis protease titer. CONCLUSIONS: In this contribution the applied PSB
      strategy performed very well for the development of B. pumilus as an alternative
      production strain. Thereby the engineered B. pumilus expression platform even
      exceeded the protease titer of the industrial production host B. licheniformis by
      14%. This result exhibits a remarkable potential of B. pumilus to be the basis
      for a next generation production host, since the strain has still a large
      potential for further genetic engineering. The final amylase titer of 65% in
      reference to B. licheniformis protease titer suggests that the developed B.
      pumilus expression platform is also suitable for an efficient production of non
      proteolytic enzymes reaching a final titer of several grams per liter without
      complex process modifications.

PMID- 24661795
TI  - Occurrence of tick-transmitted pathogens in dogs in Jos, Plateau State, Nigeria.
AB  - BACKGROUND: Canine babesiosis caused by Babesia rossi, transmitted by
      Haemaphysalis elliptica in South Africa, has also been reported from Nigeria.
      Although H. leachi (sensu lato) is widespread in sub-Saharan Africa, published
      literature on the occurrence of canine babesiosis is meagre. It has been
      postulated that the genotype of Babesia rossi Erythrocyte Membrane Antigen 1
      (BrEMA1) may be linked to virulence of the specific isolate. The primary
      objective of this study was to detect and characterise tick-borne pathogens in
      dogs presented to a veterinary hospital using molecular techniques. In B. rossi
      positive specimens, we aimed to determine whether the BrEMA1 gene occurred and to
      compare genotypes with those found in other isolates. Lastly, we wished to
      identify the tick species that were recovered from the sampled dogs. METHODS:
      Blood specimens (n = 100) were collected during January to March 2010 from
      domestic dogs presented at an animal hospital in Jos, Plateau State, Nigeria.
      They were screened for the presence of Babesia/Theileria and Ehrlichia/Anaplasma
      genomic DNA using PCR and Reverse Line Blot (RLB) assays. Positive B. rossi
      specimens were tested for the presence of the BrEMA1gene using an RT-PCR. In
      addition, ticks were collected from dogs found to be infested during sampling.
      RESULTS: On RLB, 72 (72%) of the specimens were positive for one or more
      haemoparasites. Of the positive specimens, 38 (53%) were infected with B. rossi;
      9 (13%) with Theileria sp. (sable); 5 (7%) with either Ehrlichia canis or
      Anaplasma sp. Omatjenne, respectively; 3 (4%) with Theileria equi; and 1 (1%)
      with B. vogeli and E. ruminantium, respectively. Co-infections were detected in
      13 (18%) of the specimens. Results of RT-PCR screening for the BrEMA1 gene were
      negative. A total of 146 ticks belonging to 8 species were collected and
      identified: Rhipicephalus sanguineus 107 (73%), Haemaphysalis leachi (sensu
      stricto) 27 (18%), R. turanicus 3 (2%), and Amblyomma variegatum, H. elliptica,
      R. lunulatus, R. muhsamae and R. senegalensis 1 (1%), respectively. CONCLUSIONS:
      Up to 8 tick-borne pathogens possibly occur in the dog population at Jos, with B.
      rossi being the most prevalent. The absence of the BrEMA1 gene suggests that B.
      rossi occurring in that area may be less virulent than South African isolates.

PMID- 24661797
TI  - Commercial gaming devices for stroke upper limb rehabilitation: a systematic
      review.
AB  - BACKGROUND AND PURPOSE: Rehabilitation using commercial gaming devices is a new
      concept for stroke care. Commercial gaming devices such as Nintendo Wii or Sony
      PlayStation encourage high repetition of arm movements and are being introduced
      into some clinical settings. The evidence base for gaming use in rehabilitation
      is growing rapidly and there is a need to systematically synthesise research. Our
      review aims to integrate evidence on how gaming is being used, explore
      patient/therapist experience and synthesise evidence of effectiveness. SUMMARY OF
      REVIEW: An integrative systematic review was undertaken searching Cochrane
      Central Register of Controlled Trials (2013), Medline (2013), Embase (2013) and
      twelve additional databases. Two review authors independently selected studies
      based on pre-defined inclusion criteria, extracted data and assessed risk of
      bias. Nineteen studies including 215 patients met inclusion criteria. Studies
      were typically small scale feasibility studies using a range of research designs,
      limiting the ability to reach generalised conclusions. Results have been
      tabulated (activities of daily living, upper limb function/ movement) and
      qualitative themes identified. Findings suggest that most patients enjoy using
      commercial gaming and can tolerate 180 mins per week without significant adverse
      effects. A trend towards improvement was noted for upper limb function/ movement.
      Few studies recorded outcomes related to activities of daily living or focused on
      understanding patients' experiences of this intervention. CONCLUSION: Commercial
      gaming can provide high intensity upper limb practice however there is
      insufficient high quality evidence to reach generalisable conclusions about risks
      or benefits on activities of daily living or upper limb function/movement.

PMID- 24661796
TI  - Flea control failure? Myths and realities.
AB  - Why is it that, despite the proliferation of research on their biology and
      control, fleas remain such a burden for companion animals and their owners? This
      review highlights a range of reasons for persistence and apparent treatment
      failures. It argues that a sustainable approach will require integrated pest
      management based upon a detailed understanding of the flea life cycle, targeting
      not only adult fleas but also the immature stages in the environment, combining
      several modes of control and limiting the risk of chemoresistance. Individual
      characteristics of the pet and its environment need to be considered. Control of
      fleas can be achieved, over a timescale of several months, if basic rules are
      respected. 

PMID- 24661798
TI  - Defined criteria for resectability improves rates of secondary resection after
      systemic therapy for liver limited metastatic colorectal cancer.
AB  - AIMS: Long-term survival has been demonstrated for patients with irresectable
      colorectal liver metastases who are brought to resection by chemotherapy.
      However, it remains unclear whether improved long-term outcome seen with modern
      therapies translates to increased rates of secondary resection and whether
      response rates correlate with rates of secondary liver resection. METHODS: A
      systematic review of literature published between January 1998 and September 2013
      was performed. Phase II/III trials were included if they reported the rate of
      objective response and the rate of secondary resection of initially irresectable
      metastases. For the phase III trials, the ratio between response and resection
      rates within the trials was investigated as well as the correlation for both
      parameters in all trials. RESULTS: Twenty-five studies were identified. Response
      rate demonstrated a strong correlation with rates of secondary resection
      (R(2)=0.44, p=0.008). Ratios of response/resection between both arms of 10
      randomised control trials (RCTs) were calculated to control for selection bias,
      and showed that in a randomised setting response rates correlate with increased
      rates of secondary resection in an intra-trial comparison (R(2)=0.87, p=0.002).
      Linear regression analysis demonstrated a significant difference between studies
      where criteria for resectability were defined (median 39.5%), and those where it
      was not (median 11%) (p=0.006). CONCLUSION: There is a clear correlation between
      radiological response and rates of secondary resection, with studies that define
      resectability achieving much higher rates. All trials investigating first line
      treatment in patients with metastatic colorectal cancer should have criteria for
      resection, with conversion to secondary resection as a defined study end-point.

PMID- 24661799
TI  - Validation of the Danish translation of the Medicine Knowledge Questionnaire
      among elementary school children.
AB  - BACKGROUND: There is a lack of instruments which can be used to quantitatively
      assess school children's knowledge about medicine in different countries.
      OBJECTIVES: The aim of this study was to validate the Danish translation of a
      school children's medicine knowledge questionnaire developed in Finland. METHODS:
      A total of 685 children from 37 Danish elementary schools, aged 10-14 years,
      participated in a validation study. Test-retest and inter-rater reliability, as
      well as known-group-validity of the translated instrument were investigated.
      Significance level was set at P <= 0.05. RESULTS: For test-retest reliability,
      Spearman r correlation coefficients for correct knowledge score between the two
      rounds was 0.433, P < 0.001. For inter-rater reliability, kappa for agreement in
      correct knowledge score ratings between the two raters was 0.202. For known-group
      validity, a multivariate linear regression model was run for correct knowledge
      scores, and it significantly explained 9.2% of variance (R square 0.092, P <
      0.001). Gender, school grade and use of medicine for asthma were significant
      predictors in the model. CONCLUSIONS: The translated questionnaire showed a fair
      test-retest and inter-rater reliability, as well as acceptable known-group
      validity. In order to be reliably used in further studies to evaluate school
      children's knowledge about medicine in Denmark, the methodic of knowledge scoring
      in the instrument is warranted.

PMID- 24661800
TI  - Medication review practices in European countries.
AB  - BACKGROUND: Medication review procedures have been developed in many countries to
      improve rational and safe medication use. The similarities, comprehensiveness,
      and effectiveness of these procedures has not been assessed, or compared.
      OBJECTIVE: The aim of this study was to explore medication review practices in
      European countries. METHODS: An online survey was sent to 32 European countries
      (all 28 European Union countries and 4 other European countries) by email to one
      person in each country known to be aware of medication review practices in their
      country in May 2011. The informants were identified through Pharmaceutical Group
      of European Union. To complement and validate the information received through
      Pharmaceutical Group of European Union, medication review experts involved in
      Pharmaceutical Care Network Europe were contacted. The survey assessed
      comprehensiveness of the medication review procedures classified according to 3
      types in terms of settings; access to patient clinical information; patient
      involvement; availability of documentation and information; collaboration with
      the physician; quality control, and training required. RESULTS: Almost two thirds
      (64%) of the 25 European countries which responded (response rate 78%) indicated
      having at least one type of medication review procedure in their country. In the
      community setting prescription (type I) and adherence (type II) medication
      reviews were the most common (established in 9 and 11 countries, respectively).
      More comprehensive type III clinical medication reviews requiring access to
      clinical patient information were still rare, and just being established in 6
      countries. CONCLUSIONS: Medication review procedures are becoming common in
      health care throughout Europe, however improving their comprehensiveness would
      require better access to patient information for those professionals conducting
      clinical medication reviews. In addition to benchmarking, the inventory can
      enhance cooperation between countries and stakeholders involved in medication
      review practice development nationally and internationally.

PMID- 24661801
TI  - Substance use and violence among psychiatric inpatients.
AB  - Nursing staff on psychiatric wards often attribute patient violence and
      aggression to substance use. This study examined incidents of alcohol and illicit
      drug use among acute psychiatric inpatients and associations between substance
      use and violence or other forms of aggression. A sample of 522 adult psychiatric
      inpatients was recruited from 84 acute psychiatric wards in England. Data were
      collected from nursing and medical records for the first 2 weeks of admission.
      Only a small proportion of the sample was reported to have used or been under the
      influence of alcohol (5%) or drugs (3%). There was no physical violence during a
      shift when a patient had used alcohol or drugs. Substance using patients were
      also no more likely than others to behave violently at any point during the study
      period. However, incidents of substance use were sometimes followed by verbal
      aggression. Beliefs that substance using patients are likely to be violent were
      not supported by this study, and could impact negatively on therapeutic
      relationships between nurses and this patient group. Future studies are needed to
      examine how staff intervene and interact with intoxicated patients.

PMID- 24661802
TI  - One-Health Simulation Modelling: A Case Study of Influenza Spread between Human
      and Swine Populations using NAADSM.
AB  - The circulation of zoonotic influenza A viruses including pH1N1 2009 and H5N1
      continue to present a constant threat to animal and human populations. Recently,
      an H3N2 variant spread from pigs to humans and between humans in limited numbers.
      Accordingly, this research investigated a range of scenarios of the transmission
      dynamics of pH1N1 2009 virus at the swine-human interface while accounting for
      different percentages of swine workers initially immune. Furthermore, the
      feasibility of using NAADSM (North American Animal Disease Spread Model) applied
      as a one-health simulation model was assessed. The study population included 488
      swine herds and 29, 707 households of people within a county in Ontario, Canada.
      Households were categorized as follows: (i) rural households with swine workers,
      (ii) rural households without swine workers, and (iii) urban households without
      swine workers. Forty-eight scenarios were investigated, based on the combination
      of six scenarios around the transmissibility of the virus at the interface and
      four vaccination coverage levels of swine workers (0-60%), all under two settings
      of either swine or human origin of the virus. Outcomes were assessed in terms of
      stochastic 'die-out' fraction, size and time to peak epidemic day, overall size
      and duration of the outbreaks. The modelled outcomes indicated that minimizing
      influenza transmissibility at the interface and targeted vaccination of swine
      workers had significant beneficial effects. Our results indicate that NAADSM can
      be used as a framework to model the spread and control of contagious zoonotic
      diseases among animal and human populations, under certain simplifying
      assumptions. Further evaluation of the model is required. In addition to these
      specific findings, this study serves as a benchmark that can provide useful input
      to a future one-health influenza modelling studies. Some pertinent information
      gaps were also identified. Enhanced surveillance and the collection of high
      quality information for more accurate parameterization of such models are
      encouraged.

PMID- 24661803
TI  - Papillary hidradenoma of the eyelid margin: clinical and immunohistochemical
      observations further supporting an apocrine rather than an eccrine origin.
AB  - A 46-year-old woman was evaluated for a "recurring papilloma" of the left medial
      upper eyelid margin. Beneath the papillary lesion medial to the punctum was a 5
      mm diameter cutaneous mass thought to be cystic. After excisional biopsy,
      histopathologic analysis documented the presence of an epidermal keratinizing
      squamous papilloma surmounting a circumscribed dermal papillary hidradenoma
      composed of deeply eosinophilic columnar cells. Additionally, there was
      intraductal proliferation of tumor extending toward a subclinical poral opening
      through the epidermis. Immunohistochemistry proved the apocrine nature of the
      benign, non-cystic lesion by virtue of its nuclear androgen receptor and
      cytoplasmic gross-cystic disease fluid protein-15 positivity, along with its
      smooth muscle actin-positive myoepithelial layer. This and prior cases establish
      that apocrine tumors, both benign and malignant, are strictly localized at or
      near the eyelid margin where only apocrine glands are found. These tumors are
      more often papillary than solid adenomas, and most exceptionally can be
      malignant. We review the differential diagnosis of simulating eccrine eyelid
      tumors. We recommend wide local excision for benign lesions, in view of possible
      intraductal extension that can be eccentric to the main tumor and the miniscule
      potential for malignant transformation. 

PMID- 24661804
TI  - Early selection of novel triploid hybrids of shrub willow with improved biomass
      yield relative to diploids.
AB  - BACKGROUND: Genetic improvement of shrub willow (Salix), a perennial energy crop
      common to temperate climates, has led to the development of new cultivars with
      improved biomass yield, pest and disease resistance, and biomass composition
      suitable for bioenergy applications. These improvements have largely been
      associated with species hybridization, yet little is known about the genetic
      mechanisms responsible for improved yield and performance of certain willow
      species hybrids. RESULTS: The top performing genotypes in this study,
      representing advanced pedigrees compared with those in previous studies, were
      mostly triploid in nature and outperformed current commercial cultivars. Of the
      genotypes studied, the diploids had the lowest mean yield of 8.29 oven dry Mg ha
      1 yr-1, while triploids yielded 12.65 Mg ha-1 yr-1, with the top five producing
      over 16 Mg ha-1 yr-1. Triploids had high stem area and height across all three
      years of growth in addition to greatest specific gravity. The lowest specific
      gravity was observed among the tetraploid genotypes. Height was the early trait
      most correlated with and the best predictor of third-year yield. CONCLUSIONS:
      These results establish a paradigm for future breeding and improvement of Salix
      bioenergy crops based on the development of triploid species hybrids. Stem height
      and total stem area are effective traits for early prediction of relative yield
      performance.

PMID- 24661805
TI  - The impact of health insurance on health services utilization and health outcomes
      in Vietnam.
AB  - In recent years, a number of low- and middle-income country governments have
      introduced health insurance schemes. Yet not a great deal is known about the
      impact of such policy shifts. Vietnam's recent health insurance experience
      including a health insurance scheme for the poor in 2003 and a compulsory scheme
      that provides health insurance to all children under six years of age combined
      with Vietnam's commitment to universal coverage calls for research that examines
      the impact of health insurance. Taking advantage of Vietnam's unique policy
      environment, data from the 2002, 2004 and 2006 waves of the Vietnam Household
      Living Standard Survey and single-difference and difference-in-differences
      approaches are used to assess whether access to health insurance--for the poor,
      for children and for students--impacts on health services utilization and health
      outcomes in Vietnam. For the poor and for students, results suggest health
      insurance increased the use of inpatient services but not of outpatient services
      or health outcomes. For young children, results suggest health insurance
      increased the use of outpatient services (including the use of preventive health
      services such as vaccination and check-up) but not of inpatient services.

PMID- 24661806
TI  - Nosocomial tuberculosis exposures at a tertiary care hospital: a root cause
      analysis.
AB  - BACKGROUND: Exposure of health care workers (HCWs) to patients with active TB
      continues to occur despite implementation of TB control policies. METHODS: We
      conducted a root-cause analysis of TB exposures at a tertiary care hospital.
      Clinical and management details of all confirmed cases identified in 2011 were
      summarized. Cases were independently reviewed by an expert panel that determined
      the type (ie, delay in initiating, incorrect use of or premature removal of
      control measures), preventability, and root cause(s) of each error (exposure).
      RESULTS: Fifteen cases were reviewed. Ten errors were identified in 7 (47%)
      cases. Cases associated with errors were older than those without errors (68 y vs
      40 y; P = .037). Most cases (12/15) were foreign born. A delay in initiating
      airborne precautions accounted for 70% (7/10) of the errors. The expert panel
      determined that 80% (8/10) of the errors were preventable or possibly
      preventable. The most common root causes were failure to consider TB and failure
      to obtain and interpret imaging. Advanced age, atypical presentation, and
      presence of comorbid illnesses were common among the preventable cases.
      CONCLUSIONS: TB control policies do not prevent all exposures. Our findings
      suggest that consideration of TB in elderly patients with risk factors, even if
      their signs and symptoms can be explained by an alternative diagnosis or are
      atypical, followed by a review of imaging studies, can further reduce this risk.

PMID- 24661808
TI  - Frequency of eprinomectin resistance in gastrointestinal nematodes of goats in
      canton Berne, Switzerland.
AB  - Eprinomectin (EPN) is a member of the avermectin class of compounds and the only
      anthelmintic registered for goats in Switzerland with a zero milk withdrawal
      period. The aim of the present study was to identify the actual efficacy of EPN
      in an area with a higher density of goat enterprises. Forty-three randomly chosen
      farms from canton Berne were investigated. At least eight goats were investigated
      on every farm. Conditions for inclusion in the study were the absence of
      anthelmintic treatment during the previous six weeks and a pooled faecal sample
      showing a mean faecal egg count (FEC) higher than 600 epg faeces. Pre- and 14-16
      days post-treatment samples were individually collected directly from the rectum.
      Animals were treated with the recommended dose of EPN (1 mg/kg body weight) after
      taking the pre-treatment samples. Efficacy of EPN was tested with the faecal egg
      count reduction test (FECRT) and faecal cultures were performed on every farm
      from pooled faeces samples before and after treatment. Additionally the farmers
      completed a questionnaire. None of the gastrointestinal nematode populations of
      the 43 investigated farms were susceptible to EPN at the required level. The mean
      egg count reduction was 40%. None of the typical risk factors, such as production
      type, stocking rate, animal traffic and quarantine measures showed an association
      with the level of eprinomectin resistance. It can be concluded with 80% certainty
      that the prevalence of EPN resistance on goat farms is at least 95% in canton
      Berne.

PMID- 24661807
TI  - Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C
      cirrhosis through GC/MS and UPLC/MS-MS.
AB  - BACKGROUND & AIMS: The metabolic pathway disturbances associated with
      hepatocellular carcinoma (HCC) remain unsatisfactorily characterized.
      Determination of the metabolic alterations associated with the presence of HCC
      can improve our understanding of the pathophysiology of this cancer and may
      provide opportunities for improved disease monitoring of patients at risk for HCC
      development. To characterize the global metabolic alterations associated with HCC
      arising from hepatitis C (HCV)-associated cirrhosis using an integrated non
      targeted metabolomics methodology employing both gas chromatography/mass
      spectrometry (GC/MS) and ultrahigh-performance liquid chromatography/electrospray
      ionization tandem mass spectrometry (UPLC/MS-MS). METHODS: The global serum
      metabolomes of 30 HCC patients, 27 hepatitis C cirrhosis disease controls and 30
      healthy volunteers were characterized using a metabolomics approach that combined
      two metabolomics platforms, GC/MS and UPLC/MS-MS. Random forest, multivariate
      statistics and receiver operator characteristic analysis were performed to
      identify the most significantly altered metabolites in HCC patients vs. HCV
      cirrhosis controls and which therefore exhibited a close association with the
      presence of HCC. RESULTS: Elevated 12-hydroxyeicosatetraenoic acid (12-HETE), 15
      HETE, sphingosine, gamma-glutamyl oxidative stress-associated metabolites,
      xanthine, amino acids serine, glycine and aspartate, and acylcarnitines were
      strongly associated with the presence of HCC. Elevations in bile acids and
      dicarboxylic acids were highly correlated with cirrhosis. CONCLUSIONS: Integrated
      metabolomic profiling through GC/MS and UPLC/MS-MS identified global metabolic
      disturbances in HCC and HCV-cirrhosis. Aberrant amino acid biosynthesis, cell
      turnover regulation, reactive oxygen species neutralization and eicosanoid
      pathways may be hallmarks of HCC. Aberrant dicarboxylic acid metabolism, enhanced
      bile acid metabolism and elevations in fibrinogen cleavage peptides may be
      signatures of cirrhosis.

PMID- 24661809
TI  - Enzymatic activities and effects of mycovirus infection on the virulence of
      Metarhizium anisopliae in Rhipicephalus microplus.
AB  - The present study aimed to evaluate the pathogenic potential of different
      Metarhizium anisopliae s.l. isolates and to determine whether differences in
      enzymatic activities of proteases, lipases and chitinases and infection with
      mycoviruses affect the control of Rhipicephalus microplus achieved by these
      fungal isolates. Engorged female ticks were exposed to fungal suspensions. The
      lipolytic and proteolytic activities in the isolates were evaluated using
      chromogenic substrates and the chitinolytic activity was determined using
      fluorescent substrates. A gel zymography was performed to determine the
      approximate size of serine proteases released by M. anisopliae isolates. To
      detect mycoviral infections, dsRNA was digested using both RNAse A and S1
      endonuclease; samples were analyzed on an agarose gel. Four of the five isolates
      tested were infected with mycovirus; however, the level of control of R.
      microplus ticks achieved with the only isolate free of infection (isolate CG 347)
      was low. This finding suggests that mycoviral infection does not affect the
      virulence of fungi against ticks. Although all five isolates were considered
      pathogenic to R. microplus, the best tick control and the highest levels of
      enzymatic activity were achieved with the isolates CG 629 and CG 148. The in
      vitro activities of lipases, proteases and chitinases produced by M. anisopliae
      s.l. differed among isolates and may be related to their virulence. 

PMID- 24661810
TI  - Lotus japonicus SUNERGOS1 encodes a predicted subunit A of a DNA topoisomerase VI
      that is required for nodule differentiation and accommodation of rhizobial
      infection.
AB  - A symbiotic mutant of Lotus japonicus, called sunergos1-1 (suner1-1), originated
      from a har1-1 suppressor screen. suner1-1 supports epidermal infection by
      Mesorhizobium loti and initiates cell divisions for organogenesis of nodule
      primordia. However, these processes appear to be temporarily stalled early during
      symbiotic interaction, leading to a low nodule number phenotype. This defect is
      ephemeral and near wild-type nodule numbers are reached by suner1-1 at a later
      point after infection. Using an approach that combined map-based cloning and next
      generation sequencing we have identified the causative mutation and show that the
      suner1-1 phenotype is determined by a weak recessive allele, with the
      corresponding wild-type SUNER1 locus encoding a predicted subunit A of a DNA
      topoisomerase VI. Our data suggest that at least one function of SUNER1 during
      symbiosis is to participate in endoreduplication, which is an essential step
      during normal differentiation of functional, nitrogen-fixing nodules. 

PMID- 24661812
TI  - Simultaneous utilization of glucose and mannose from spent yeast cell mass for
      lipid production by Lipomyces starkeyi.
AB  - With ever-increasing culture of yeasts for the production of biofuels and other
      metabolites, spent yeast cell mass exceeds its traditional market demands. Yeast
      cell mass contains glucose, mannose and other sugars that may be utilized for
      microbial culture. Here we demonstrated that the oleaginous yeast Lipomyces
      starkeyi could utilize glucose and mannose simultaneously for lipid production.
      Overall substrate consumption rates and lipid coefficients were 0.58 g/L/h and
      0.18 g lipid/g sugar, respectively, in flask cultures regardless of glucose,
      mannose or a mixture of both as the carbon source. L. starkeyi grew well on the
      hydrolysates of spent cell mass of Rhodosporidium toruloides, consumed both
      glucose and mannose therein, and produced lipid at a yield of 0.12 g lipid/g
      total reducing sugars. This co-utilization strategy expands carbon sources for
      lipid production. It should provide an opportunity for recycling spent cell mass
      and be of significant interests to biorefinery and biofuel production.

PMID- 24661811
TI  - Peripheral arterial disease, gender, and depression in the Heart and Soul Study.
AB  - BACKGROUND: Despite the high prevalence of peripheral arterial disease (PAD) in
      women, risk factors for PAD in women are not well understood. METHODS: Gender
      specific risk factors for PAD were examined in a prospective cohort study of 1024
      patients (184 women and 840 men) with stable coronary artery disease who were
      recruited between 2000 and 2002. Logistic regression models were used to evaluate
      associations between traditional and nontraditional risk factors and PAD in men
      and women. RESULTS: PAD was found in 11% of women and in 13% of men. Women with
      PAD had a similar prevalence of traditional risk factors (hypertension,
      hyperlipidemia, and smoking) compared with women without PAD and were
      significantly more likely to suffer from depression than women without PAD. Men
      with PAD were more likely to have hypertension, diabetes mellitus, a history of
      smoking, a worse lipid profile, and higher levels of inflammatory biomarkers than
      men without PAD. A multivariate model showed depression was the strongest
      independent factor associated with PAD in women, whereas smoking and elevated
      fibrinogen were independently associated with PAD in men. CONCLUSIONS: The
      current findings suggest there are gender differences in risk factors for the
      development of PAD. Further research is needed to understand the role of
      depression in PAD.

PMID- 24661813
TI  - Preparation of a novel carbon-based solid acid from cassava stillage residue and
      its use for the esterification of free fatty acids in waste cooking oil.
AB  - A novel carbon-based solid acid catalyst was prepared by the sulfonation of
      incompletely carbonized cassava stillage residue (CSR) with concentrated sulfuric
      acid, and employed to catalyze the esterification of methanol and free fatty
      acids (FFAs) in waste cooking oil (WCO). The effects of the carbonization and the
      sulfonation temperatures on the pore structure, acid density and catalytic
      activity of the CSR-derived catalysts were systematically investigated. Low
      temperature carbonization and high temperature sulfonation can cause the collapse
      of the carbon framework, while high temperature carbonization is not conducive to
      the attachment of SO3H groups on the surface. The catalyst showed high catalytic
      activity for esterification, and the acid value for WCO is reduced to below 2mg
      KOH/g after reaction. The activity of catalyst can be well maintained after five
      cycles. CSR can be considered a promising raw material for the production of a
      new eco-friendly solid acid catalyst. 

PMID- 24661814
TI  - Promoter and signal sequence from filamentous fungus can drive recombinant
      protein production in the yeast Kluyveromyces lactis.
AB  - Cross-recognition of promoters from filamentous fungi in yeast can have important
      consequences towards developing fungal expression systems, especially for the
      rapid evaluation of their efficacy. A truncated 510bp inducible Trichoderma
      reesei cellobiohydrolase I (cbh1) promoter was tested for the expression of green
      fluorescent protein (GFP) in Kluyveromyces lactis after disrupting its native
      beta-galactosidase (lac4) promoter. The efficiency of the CBH1 secretion signal
      was also evaluated by fusing it to the lac4 promoter of the yeast, which
      significantly increased the secretion of recombinant protein in K. lactis
      compared to the native alpha-mating factor secretion signal. The fungal promoter
      is demonstrated to have potential to drive heterologous protein production in K.
      lactis; and the small sized T. reesei cbh1 secretion signal can mediate the
      protein secretion in K. lactis with high efficiency. 

PMID- 24661815
TI  - A comparison study on membrane fouling in a sponge-submerged membrane bioreactor
      and a conventional membrane bioreactor.
AB  - This study compared membrane fouling in a sponge-submerged membrane bioreactor
      (SSMBR) and a conventional membrane bioreactor (CMBR) based on sludge properties
      when treating synthetic domestic wastewater. In the CMBR, soluble microbial
      products (SMP) in activated sludge were a major contributor for initial membrane
      fouling and presented higher concentration in membrane cake layer. Afterwards,
      membrane fouling was mainly governed by bound extracellular polymeric substances
      (EPS) in activated sludge, containing lower proteins but significantly higher
      polysaccharides. Sponge addition could prevent cake formation on membrane surface
      and pore blocking inside membrane, thereby alleviating membrane fouling. The
      SSMBR exhibited not only less growth of the biomass and filamentous bacteria, but
      also lower cake layer and pore blocking resistance due to lower bound EPS
      concentrations in activated sludge. Less membrane fouling in SSMBR were also
      attributed to larger particle size, higher zeta potential and relative
      hydrophobicity of sludge flocs. 

PMID- 24661816
TI  - How we determined the most reliable solid medium for studying treatment of
      tuberculosis.
AB  - Phase 2 clinical trials for tuberculosis (TB) treatment require reliable culture
      methods to determine presence or absence of Mycobacterium tuberculosis (Mtb) over
      the course of therapy, as these trials are based primarily on bacteriological
      endpoints. We evaluate which of 5 solid media is most reliable: Lowenstein-Jensen
      (LJ) egg-base medium and 4 Middlebrook agar media (nonselective 7H10 and 7H11 and
      selective 7H10 and 7H11). We analyze 393 specimens from 50 HIV-negative Ugandan
      adults with newly-diagnosed, pulmonary TB and high acid-fast bacillus smear
      grade. Specimens were collected every 2-4 weeks during the first 12 weeks of
      therapy. We compare the results for each culture to 2 composite reference
      standards--one that was deemed positive if any solid culture was positive for Mtb
      and another based on latent-class analysis. Both reference standards established
      that the 2 selective Middlebrook media most reliably determine the presence or
      absence of Mtb (P < 0.003), largely because of their lower contamination rates.
      We also showed that results on Middlebrook media were similar to each other,
      while LJ was most frequently discordant. Contaminated results appeared more
      likely to be truly negative than to harbor undetected Mtb.

PMID- 24661817
TI  - HEPBURN - investigating the efficacy and safety of nebulized heparin versus
      placebo in burn patients with inhalation trauma: study protocol for a multi
      center randomized controlled trial.
AB  - BACKGROUND: Pulmonary coagulopathy is a hallmark of lung injury following
      inhalation trauma. Locally applied heparin attenuates lung injury in animal
      models of smoke inhalation. Whether local treatment with heparin benefits
      patients with inhalation trauma is uncertain. The present trial aims at comparing
      a strategy using frequent nebulizations of heparin with standard care in
      intubated and ventilated burn patients with bronchoscopically confirmed
      inhalation trauma. METHODS: The Randomized Controlled Trial Investigating the
      Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with
      Inhalation Trauma (HEPBURN) is an international multi-center, double-blind,
      placebo-controlled, two-arm study. One hundred and sixteen intubated and
      ventilated burn patients with confirmed inhalation trauma are randomized to
      nebulizations of heparin (the nebulized heparin strategy) or nebulizations of
      normal saline (the control strategy) every four hours for 14 days or until
      extubation, whichever comes first. The primary endpoint is the number of
      ventilator-free days, defined as days alive and breathing without assistance
      during the first 28 days, if the period of unassisted breathing lasts for at
      least 24 consecutive hours. DISCUSSION: As far as the authors know, HEPBURN is
      the first randomized, placebo-controlled trial, powered to investigate whether
      local treatment with heparin shortens duration of ventilation of intubated and
      ventilated burn patients with inhalation trauma. TRIAL REGISTRATION: NCT01773083
      (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting.
      Randomisation commenced on 1 January 2014.

PMID- 24661818
TI  - The diagnostic utility of Sudoscan for distal symmetric peripheral neuropathy.
AB  - AIMS: Diagnosis of early distal symmetric polyneuropathy (DSP) is challenging.
      Nerve conduction studies (NCS) are often normal. Skin biopsy for intraepidermal
      nerve fiber density (IENFD) has better sensitivity, but is invasive. Sudoscan is
      a novel technology that measures electrochemical skin conductance (ESC;
      microSiemens, MUS), which is thought to be proportionate to the number of
      functional sweat glands. This study evaluated Sudoscan's diagnostic utility for
      DSP. METHODS: 55 patients with suspected DSP (22 with diabetes, 2 prediabetes, 31
      idiopathic) and 42 controls underwent the Utah Early Neuropathy Scale (UENS) and
      Sudoscan. Each was offered skin biopsy. DSP participants underwent quantitative
      sudomotor axon reflex testing (QSART) and NCS. RESULTS: Feet and hands ESCs were
      reduced among DSP participants compared to controls (64+/-22 vs. 76+/-14 MUS
      p<0.005, and 58+/-19 vs. 66+/-18 MUS p<0.04). There was no difference between
      diabetic and idiopathic DSP. Receiver operating characteristic curve analysis
      revealed feet ESC and IENFD had similar areas under the curve (0.761 and 0.752).
      ESC correlated with Sural amplitude (0.337, p<0.02), UENS (-0.388, p<0.004), and
      MNSI (-0.398, p<0.005). CONCLUSIONS: Sudoscan is a promising diagnostic test for
      diabetic and idiopathic DSP, with diagnostic performance similar to IENFD.

PMID- 24661819
TI  - The relevance of living supports on antiplatelet adherence and trial
      participation: the SPS3 trial.
AB  - BACKGROUND: While living with others has been associated with improved functional
      outcome after acute stroke, it is unclear if this affects adherence to stroke
      prevention measures. AIMS: We examined the relationship between living
      arrangements and adherence to antiplatelet therapy assignment and participation
      status in an international randomized trial for secondary stroke prevention.
      METHOD: Antiplatelet therapy adherence, trial retention outcomes, and baseline
      characteristics for participants enrolled in the Secondary Prevention of Small
      Subcortical Strokes study were compared between those who lived alone vs. with
      others (n = 2374). Participant status at end-of-trial was categorized into (1) on
      assigned antiplatelet, (2) off assigned antiplatelet by participant request, or
      (3) participant withdrew consent/lost to follow-up. Multivariable multivariate
      logistic regression was used to identify patient features at entry predictive of
      participant status at trial end. RESULTS: Living arrangement, alone vs. with
      other(s), was not significantly associated with participant status. Participants
      enrolled in the United States/Canada (odds ratio 3.1, confidence intervals 2.0
      5.0, vs. Latin America), taking more (7+) prescription medications (odds ratio
      1.7, confidence intervals 1.1-2.7, vs. 0-2 medications), and scoring lower on the
      Stroke Specific Quality of Life scale (odds ratio 1.3, confidence intervals 1.1
      1.5, per 10 points) were more likely to withdraw or become lost to follow-up in
      the study vs. completing the study on assigned antiplatelet therapy. Participants
      enrolled in the United States/Canada (odds ratio 5.0, confidence intervals 2.4
      10.0, vs. Latin America) and taking fewer (0-2) medications (odds ratio 1.9,
      confidence intervals 1.2-3.1 vs. 3-6 medications) were more likely to request
      discontinuation of assigned antiplatelet medication vs. completing the study.
      CONCLUSION: Living with others was not independently predictive of protocol
      adherence in this cohort. Number of medications and Stroke Specific Quality of
      Life scale score may be more indicative of likelihood of trial participation and
      acceptance of long-term antiplatelet regimen.

PMID- 24661820
TI  - Antifungal stewardship in invasive Candida infections.
AB  - Bloodstream and other invasive infections due to Candida species (invasive fungal
      diseases = IFD) are a major cause of morbidity and mortality in hospitalized
      adults and children in many countries worldwide. The high infection-related
      morbidity and mortality associated with invasive Candida infection/candidaemia
      (IC/C), combined with suboptimal diagnostic tools, have driven the overuse of
      antifungal drugs. Antifungal stewardship (AFS) may be regarded as subentity of
      the more general term Anti-infective or Antimicrobial Stewardship Program
      (AIS/AMS). The high costs and high contribution of antifungal agents to the
      management of IFDs along with their recognized toxicities have been addressed as
      the principal justification for antifungal stewardship. AFS programmes should be
      organized by an interdisciplinary team of clinicians, pharmacists,
      microbiologists and infection control experts with the lead of an infectious
      disease specialist preferably in each large hospital/institution dealing with
      high-risk patients for invasive fungal infections. These programmes should
      consider various aspects of IC/C including (i) the local fungal epidemiology,
      (ii) information on antifungal resistance rates, (iii) establishing and
      application of therapeutic guidelines, (iv) implementation of treatment
      strategies for empirical, pre-emptive therapy including PK/PD data for antifungal
      drugs, de-escalation and 'switch and step-down strategies' (from intravenous to
      oral medication) in defined patient populations, (v) catheter management together
      with the application of routine diagnostic procedures such as ophthalmological
      and cardiac evaluations and (vi) the best available diagnostic tests for
      diagnosing IC and candidaemia.

PMID- 24661821
TI  - Do prior histories of violence and mental disorders impact on violent behaviour
      during encounters with police?
AB  - Despite sustained large-scale educational campaigns, public attitudes towards
      mental illness have remained persistently negative. Associated with this, recent
      research from Victoria, Australia, reported that police commonly associated
      violent behaviour with mental illness. The present study examined 4267 cases of
      police use of force and considered what differentiated and characterised violent
      from non-violent behaviours reported by police in the context of a use of force
      incident. The specific focus was to examine the effects that historical variables
      such as age, gender, prior violent offending and having a prior diagnosis of
      mental disorder, as well as incident specific factors such as exhibiting signs of
      mental disorder and substance intoxication have on violent behaviour during the
      use of force incident. The proximal factors of apparent mental disorder and
      alcohol intoxication were significantly associated with violent behaviour towards
      police, whilst having a history of prior violence and prior mental disorder
      diagnoses was not associated with violence. The results challenge traditional
      stereotyped views about the violence risk posed by people with prior contact with
      mental health services and those with prior violent offending histories. A
      service model that allows for psychiatric triage would be able to assist with
      streamlining police involvement and facilitating timely access to mental health
      services. 

PMID- 24661822
TI  - Papular dermatitis due to Leishmania infantum infection in seventeen dogs:
      diagnostic features, extent of the infection and treatment outcome.
AB  - : BACKGROUND: This study describes immunological responses, diagnostic features,
      follow up and treatment outcomes from seventeen dogs with papular dermatitis due
      to Leishmania infection diagnosed by cytology or real time-PCR. METHODS: Specific
      Leishmania humoral and cellular immune responses were evaluated by means of an
      immunofluorescence antibody test in all cases and a delayed-type hypersensitivity
      (DTH) reaction to leishmanin in eight cases. The extent of infection was studied
      in several tissues including blood, lymph node, conjunctival and oral swabs, by
      means of PCR, at the time of diagnosis and during follow-up. Culture was
      performed on nine dogs from cutaneous lesions and lymph node aspirates and
      molecular typing was carried out on isolates based on ITS-1, ITS-2 and Haspb gene
      sequencing analysis. RESULTS: Cytological and molecular results from fine needle
      aspirates of papules were diagnostic in 8 out of 13 (61.5%) cases and in 14 out
      of 15 dogs (93.3%), respectively. In all dogs, specific anti-Leishmania antibody
      levels were low or absent. Blood and lymph node PCRs and lymph node culture were
      negative in all dogs. Three out of the nine dogs (33%) were positive by culture
      from cutaneous lesions. The three isolates were identified as ITS type A,
      however, polymorphism was observed in the Haspb gene (PCR products of 626 bp, 962
      bp and 371 bp). DTH response was positive in all tested dogs at the time of
      diagnosis. The majority of dogs were successfully treated with only N
      methylglucamine antimoniate, after which cutaneous lesions disappeared or were
      reduced to depigmented, flattened scars. All dogs remained seronegative and the
      majority of dogs were negative by PCR in several tissues during follow-up.
      CONCLUSIONS: This study points out that papular dermatitis due to L. infantum is
      probably an underestimated benign cutaneous problem, associated with a parasite
      specific cell mediated immunity and a poor humoral immune response. Papular
      dermatitis is seen in young dogs, and appears to be a mild disease with
      restricted parasite dissemination and a good prognosis. PCR can be used as a non
      invasive method to routinely evaluate papules if Leishmania infection is
      suspected in cases in which parasites are not visualized by cytology.

PMID- 24661824
TI  - Value of knowledge-based iterative model reconstruction in low-kV 256-slice
      coronary CT angiography.
AB  - BACKGROUND: Most current iterative reconstruction algorithms for CT imaging are a
      mixture of iterative reconstruction and filtered back projection. The value of
      "fully" iterative reconstruction in coronary CT angiography remains poorly
      understood. OBJECTIVE: We aimed to assess the value of the knowledge-based
      iterative model reconstruction (IMR) algorithm on the qualitative and
      quantitative image quality at 256-slice cardiac CT. METHODS: We enrolled 21
      patients (mean age: 69 +/- 11 years) who underwent retrospectively ECG gated
      coronary CT anhgiography at 100 kVp tube voltage. Images were reconstructed with
      the filtered back projection (FBP), hybrid iterative reconstruction (IR), and IMR
      algorithms. CT attenuation and the contrast-to-noise ratio (CNR) of the coronary
      arteries were calculated. With the use of a 4-point scale, 2 reviewers visually
      evaluated the coronary arteries and cardiac structures. RESULTS: The mean CT
      attenuation of the proximal coronary arteries was 369.3 +/- 73.6 HU, 363.9 +/-
      75.3 HU, and 363.3 +/- 74.5 HU, respectively, for FBP, hybrid IR, and IMR and was
      not significantly different. The image noise of the proximal coronary arteries
      was significantly lower with IMR (11.3 +/- 2.8 HU) than FBP (51.9 +/- 12.9 HU)
      and hybrid IR (23.2 +/- 5.2 HU). The mean CNR of the proximal coronary arteries
      was 9.4 +/- 2.4, 20.2 +/- 4.7, and 41.8 +/- 9.5 with FBP, hybrid IR and IMR,
      respectively; it was significantly higher with IMR. The best subjective image
      quality for coronary vessels was obtained with IMR (proximal vessels: FBP, 2.6 +/
      0.5; hybrid IR, 3.4 +/- 0.5; IMR, 3.8 +/- 0.4; distal vessels: FBP, 2.3 +/- 0.5;
      hybrid IR. 3.1 +/- 0.5; IMR, 3.7 +/- 0.5). IMR also yielded the best
      visualization for cardiac systems, that is myocardium and heart valves.
      CONCLUSION: The novel knowledge-based IMR algorithm yields significantly improved
      CNR and better subjective image quality of coronary vessels and cardiac systems
      with reliable CT number measurements for cardiac CT imaging.

PMID- 24661823
TI  - Rationale and design of the PREDICT (Plaque Registration and Evaluation Detected
      In Computed Tomography) registry.
AB  - BACKGROUND: At least two-thirds of cases of acute coronary syndrome are caused by
      disruption of an atherosclerotic plaque. The natural history of individual
      plaques is unknown and needs to be established. OBJECTIVES: The Plaque
      Registration and Evaluation Detected In Computed Tomography (PREDICT) registry is
      a prospective, multicenter, longitudinal, observational registry. This registry
      was designed to examine the relationships among coronary CT angiography (CTA)
      findings and clinical findings, mortality, and morbidity. The relationships among
      progression of coronary atherosclerosis, including changes in plaque
      characteristics on coronary CTA, and serum lipid levels and modification of
      coronary risk factors will also be evaluated. METHODS: From October 2009 to
      December 2012, 3015 patients who underwent coronary CTA in 29 centers in Japan
      were enrolled. These patients were followed for 2 years. The primary end points
      were considered as all-cause mortality and major cardiac events, including
      cardiac death, nonfatal myocardial infarction, and unstable angina that required
      hospitalization. The secondary end points were heart failure that required
      administration of diuretics, target vessel revascularization, cerebral
      infarction, peripheral arterial disease, and invasive coronary angiography. Blood
      pressure, serum lipid, and C-reactive protein levels and all cardiovascular
      events were recorded at 1 and 2 years. If the initial coronary CTA showed any
      stenosis or plaques, follow-up coronary CTA was scheduled at 2 years to determine
      changes in coronary lesions, including changes in plaque characteristics.
      CONCLUSION: Analysis of the PREDICT registry data will clarify the relationships
      between coronary CTA findings and cardiovascular mortality and morbidity in a
      collaborative multicenter fashion. This trial is registered at
      www.clinicaltrials.gov as NCT 00991835.

PMID- 24661825
TI  - Image quality and radiation exposure of coronary CT angiography in patients after
      coronary artery bypass graft surgery: influence of imaging direction with 64
      slice dual-source CT.
AB  - BACKGROUND: The evaluation of native coronary arteries (NCAs) as well as coronary
      artery bypass graft (CABG) patency after surgery is essential. However, NCAs are
      often blurred in the craniocaudal scan direction because of long scan time with
      64-slice CT. OBJECTIVE: The purpose of the study was to determine the effect of
      scan direction on image quality and radiation exposure in assessment of NCAs and
      CABGs. METHODS: Retrospective analysis of 191 consecutive individuals undergoing
      coronary CT angiography to evaluate CABG patency using 64-slice dual source CT. A
      retrospectively ECG gated spiral acquisition protocol with ECG based tube current
      modulation and automatic adjustment of tube current to a reference of 320 mAs
      ("CareDose 4D") was used. Tube current was 120 kVp. Scan direction was either
      cranio-caudal (CRC, n = 98) or caudo-cranial (CRC, n = 93) and the scan volume
      covered the entire course of all bypass grafts. Independent investigators
      determined quantitative image quality of the coronary arteries by evaluating
      contrast-to-noise ratio (CNR), radiation exposure by comparing the effective
      dose, and qualitative image quality through a 5 point rating scale. RESULTS:
      Quantitative image quality was not significantly different for the two groups
      except for the CNR of the right coronary artery which was significantly higher in
      patients with caudio-cranial scan direction (P = .0007). The qualitative image
      quality of the CaC group also was better for both NCAs and CABGs (P = .002 for
      NCAs and <.001 for CABGs), mostly because of the lower frequency of respiration
      artifacts on coronary arteries of the CaC group (P = .005). As an effect of
      automatic tube current adjustment, radiation dose was lower in patients with
      caudo-cranial scan direction (6.8 mSv vs. 9.6 mSv, p < 0.0001). CONCLUSION: In
      patients with coronary bypass grafts imaged by 64-slice dual source CT with
      spiral acquisition and automated tube current adjustment, a caudo-cranial scan
      direction results in improved image quality and reduced radiation exposure.

PMID- 24661826
TI  - The aortic valve calcium nodule score (AVCNS) independently predicts paravalvular
      regurgitation after transcatheter aortic valve replacement (TAVR).
AB  - BACKGROUND: Paravalvular regurgitation (PVR) is an important predictor of
      mortality after transcatheter aortic valve replacement (TAVR). Aortic valve (AV)
      calcification is strongly associated with PVR. OBJECTIVES: This study proposes a
      new metric to quantify AV total calcium burden and its composition in large
      calcium nodules (CNs) and explores its relation with PVR after TAVR. METHODS: In
      133 patients that underwent TAVR, calcium burden of the AV was quantified with
      multidetector row CT as calcium mass. Each CN was characterized. The AV CN score
      (AVCNS) was defined as AV calcium mass * mass of the largest CN. PVR was assessed
      with echocardiography at 1 month. Logistic regression analysis was conducted to
      identify predictors of PVR. RESULTS: Mean age was 84.1 +/- 7.6 years (56% women).
      TAVR access was transapical in 56%. Procedural success was achieved in 92%. In
      hospital mortality was 5%. At follow-up, the prevalence of absent/trace, mild,
      moderate, and severe PVR was 58%, 31%, 11%, and 0%, respectively. The only
      independent predictors of at least mild PVR were AVCNS (odds ratio [OR], 2.269;
      95% CI, 1.433-3.593; P < .001), number of CNs on aortic annulus (OR, 1.822; 95%
      CI, 1.137-2.921; P = .013), and aortic annulus area (OR, 1.112; 95% CI, 1.010
      1.223; P = .030). This model showed an area under the curve of 0.895 (95% CI,
      0.830-0.960) for PVR prediction. CONCLUSIONS: AVCNS, a variable that comprises
      the total burden of AV calcification as well as calcification agglomeration in
      form of large nodules, is a novel and powerful independent predictor of PVR after
      TAVR.

PMID- 24661827
TI  - Accuracy of coronary computed tomography angiography vs intravascular ultrasound
      for evaluation of vessel area.
AB  - BACKGROUND: We evaluated the accuracy of commonly used thresholds for vessel area
      evaluation on coronary CT angiography (CTA) and assessed ability of CTA to image
      the adventitial border. METHODS: We evaluated 137 paired (coronary CTA and
      intravascular ultrasound [IVUS]) coronary artery cross-sections in 30 patients.
      CTA analysis included measurements of external vessel border area defined at
      Hounsfield unit (HU) thresholds of 0 (presumed adventitia), 50, and 70 (presumed
      external elastic membrane [EEM]). IVUS analysis included measurements of lumen,
      EEM, and outer border of the highly echogenic area adjacent to EEM (presumed
      adventitia area). RESULTS: High correlation was found between CTA and IVUS
      measurements for EEM areas (R(2) = 0.65, P < .001 and R(2) = 0.60, P < .001 for
      CTA thresholds of 50 and 70 HU, respectively). CTA and IVUS measurements of
      adventitia areas were significantly correlated (R(2) = 0.74; P < .001), with no
      significant difference between the 2 methods (20.2 +/- 6.4 mm(2) vs 19.8 +/- 6.4
      mm(2), respectively; P = .278). Cross-sectional coronary lumen radiodensity on
      CTA images and plaque burden measured on IVUS significantly affected the accuracy
      of CTA in assessment of the EEM area but not the presumed adventitial area.
      CONCLUSIONS: We have demonstrated that use of a 50-HU threshold for vessel area
      determination by CTA led to its significant overestimation, whereas 70-HU
      threshold was close to that of EEM on IVUS. CTA may accurately delineate the
      coronary adventitial border by using a 0-HU threshold.

PMID- 24661828
TI  - Cardiovascular CT in the diagnosis of pericardial constriction: predictive value
      of inferior vena cava cross-sectional area.
AB  - BACKGROUND: The diagnosis of pericardial constriction remains challenging.
      PURPOSE: We sought to evaluate the predictive value of cardiovascular CT-based
      measurements of inferior vena cava (IVC) parameters in the diagnosis of
      pericardial constriction. METHODS: Forty-two consecutive patients referred for
      assessment of pericardial constriction by 64-slice CT were evaluated. The
      diagnosis of pericardial constriction was confirmed by clinical history,
      echocardiography, cardiac catheterization, intraoperative findings,
      histopathology, or a combination. Diameter and cross-sectional area of the
      suprahepatic IVC and cross-sectional area of the aorta were measured on a single
      axial CT image at the level of the esophageal hiatus. Maximum pericardial
      thickness was measured. Logistic regression and receiver operating curve analyses
      were performed. RESULTS: Twenty-two patients had pericardial constriction. Mean
      age of the 42 patients was 57.1 +/- 16.4 years, 57.1% were men. IVC diameter, IVC
      area, the ratio of IVC to aortic area, and pericardial thickness were all
      significantly greater in patients with constriction than in patients without (P <
      .05 for all). IVC-to-aortic area ratio had the highest odds ratio (51; 95% CI,
      2.8-922) for the prediction of constriction and remained a significant predictor
      in multivariable analysis. In nested models, IVC-to-aortic area ratio had
      incremental value over pericardial thickness for the diagnosis of constriction.
      IVC-to-aortic area ratio discriminated between patients with and without
      constriction with an area under the curve of 0.88 on receiver operating curve
      analysis, with a value >= 1.6 having a sensitivity and specificity of 95% and
      76%, respectively. Interobserver agreement for IVC-to-aortic area ratio was
      excellent (intraclass correlation coefficient, 0.98). CONCLUSION: Assessment of
      IVC-to-aortic area ratio on CT aids with the diagnosis of pericardial
      constriction and has independent and incremental value over pericardial thickness
      alone.

PMID- 24661830
TI  - CT characterization of myocardial substrate in hypertrophic cardiomyopathy.
AB  - We present a case that demonstrates myocardial fibrosis detected on a cardiac
      computed tomography study performed for the evaluation of chest pain in a patient
      with hypertrophic cardiomyopathy. We describe the correlation between
      echocardiographic strain imaging, quantitative positron emission tomography, and
      computed tomographic evidence of fibrosis and its implications in hypertrophic
      cardiomyopathy. 

PMID- 24661829
TI  - The time-adjusted gradual replacement injection method enables better
      visualization of the right heart.
AB  - BACKGROUND: Despite the improvement of cardiac CT, right heart visualization
      remains challenging. OBJECTIVE: We herein describe a new method, called the time
      adjusted gradual replacement injection protocol. The aim of this study was to
      compare this protocol with the split-bolus injection protocol. METHODS: Fifty-two
      patients who had undergone dual-source cardiac CT were retrospectively recruited.
      Twenty-six patients were injected by using the split-bolus injection protocol,
      and 26 patients were injected by using the time-adjusted gradual replacement
      injection protocol. For this method, we injected contrast medium for 10 seconds
      at a flow rate of 0.07 * body weight mL/s, then gradually replaced the contrast
      material with saline until 2 seconds before finishing the scans. The CT
      attenuation was measured in 4 chambers, the aorta, and the coronary arteries. The
      visualization of the anatomic structures and the occurrence and severity of
      streak artifacts were scored for the cardiac structures in the heart. For the
      analyses, either Welch t-test or Student t-test was performed. RESULTS: In the
      right heart, the CT values and visualization scores were significantly higher in
      the time-adjusted replacement injection group than in the split-bolus injection
      group, whereas the artifact scores were comparable between the 2 groups. The CT
      values, visualization scores, and artifact scores of the left heart were not
      significantly different between the 2 groups. CONCLUSIONS: In this study, the
      time-adjusted gradual replacement injection protocol provided excellent
      attenuation for visualization of the right heart. This method may help to
      accurately evaluate the right cardiac anatomy and thereby identify any potential
      diseases.

PMID- 24661831
TI  - 4D-cine CT imaging of a bicuspid pulmonary valve.
AB  - A 71-year-old woman underwent diagnostic workup for progressive shortness of
      breath. Transthoracic echocardiography showed a dilated main pulmonary artery
      (MPA) and an anomalous configuration of the pulmonary valve. CT revealed a
      bicuspid pulmonary valve (BPV) and confirmed MPA dilation. Further congenital
      abnormalities were excluded. An isolated finding of BPV is rather rare. To our
      knowledge we present the first 4-dimensional CT images of a BPV. As in this case,
      4-dimensional cine cardiac CT may be helpful to reveal the underlying cause of
      MPA dilation. 

PMID- 24661832
TI  - Outcomes among patients requiring unplanned intra-aortic balloon pump reinsertion
      in cardiogenic shock.
AB  - INTRODUCTION: The intra-aortic balloon pump (IABP) is the most frequently
      utilized form of temporary mechanical circulatory support (MCS) in cardiogenic
      shock (CS). Withdrawal of IABP support may precipitate hemodynamic compromise
      such that IABP reinsertion is required. Data are scarce regarding the incidence
      and outcomes of patients undergoing IABP reinsertion in this setting. METHODS: In
      this single-center retrospective study, we identified consecutive patients with
      CS in whom IABP reinsertion was required for hemodynamic decompensation. These
      patients were compared to matched controls in whom IABP withdrawal was
      successful. The primary outcome measure was in-hospital mortality, while the
      secondary outcome measure was a composite of in-hospital death, need for advanced
      MCS or heart transplantation, or discharge to hospice. RESULTS: Among 222
      patients requiring IABP for CS, we identified 20 case patients (incidence=9.0%)
      and 38 matched controls. Baseline characteristics were similar for the two
      groups. In-hospital mortality was 70% in the reinsertion group and 31% in the
      controls (Odds ratio (OR) 5.2, 95% CI 1.4-18.9, P=0.005). The composite secondary
      endpoint was also significantly more common in the reinsertion group than the
      controls (85% vs. 42%; OR 7.3, 95% CI 1.6-33.1, P=0.002). On multivariate
      analysis, the need for IABP reinsertion was independently associated with in
      hospital mortality (OR 7.7, 95% CI 1.6-36.2, P=0.01). CONCLUSION: Among patients
      with CS undergoing IABP removal, hemodynamic deterioration requiring IABP
      reinsertion is associated with extremely poor outcomes and, in appropriate
      patients, should prompt consideration of more advanced cardiac support.

PMID- 24661833
TI  - Prevalence, Isolation and Molecular Characterization of Bartonella Species in
      Republic of Korea.
AB  - To determine the prevalence of Bartonella species and identify which species of
      Bartonella naturally infects the striped field mouse (Apodemus agrarius) in the
      Republic of Korea (ROK), spleens from 200 mice were assayed by nested polymerase
      chain reaction (nPCR) targeting the RNA polymerase subunit beta (rpoB) gene and
      the 16S-23S internal transcribed spacer (ITS) region for members of the genus
      Bartonella. Utilizing PCR techniques, the prevalence of Bartonella spp. ranged
      from 31.5% (63/200) to 62.0% (124/200) for the rpoB and ITS gene fragments,
      respectively. The most prevalent species, Bartonella grahamii, was assigned to 17
      genotypes and closely related to the zoonotic pathogens, B. taylorii, B.
      tribocorum, B. phoceensis and B. henselae, which also were detected. Two
      Bartonella isolates (KRBG28 and KRBG32) were recovered from blood of A. agrarius
      captured in Gyeonggi Province, ROK. Comparison of the 16S rRNA, hemin-binding
      protein E (hbpE), glutamate dehydrogenase 1 (gdh1), invasion-associated protein B
      (ialB), cell division protein (ftsZ), citrate synthase (gltA), 60 kDa heat shock
      protein (groEL), rpoB gene fragments and the ITS region sequences from the
      isolates with GenBank was confirmed as B. grahamii. Phylogenetic analysis based
      on the alignment of concatenated sequences (4933 bp) of KRBG28 and KRBG32
      clustered with B. grahamii, forming an independent clade between Asian and
      American/European B. grahamii genogroups. 

PMID- 24661834
TI  - B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in
      addition to coronary artery calcification.
AB  - BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac
      dysfunction that is released from myocytes in response to ventricular wall
      stress. Previous studies suggested that BNP predicts stroke events in addition to
      classical risk factors. It was suggested that the BNP-associated risk results
      from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six
      hundred and seventy five subjects from the population-based Heinz Nixdorf Recall
      study (45-75 years; 47.6% men) without previous stroke, coronary heart disease,
      myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators
      were followed up over 110.1 +/- 23.1 months. Cox proportional hazards regressions
      were used to examine BNP as a stroke predictor in addition to vascular risk
      factors (age, gender, systolic blood pressure, low-density lipoprotein, high
      density lipoprotein, diabetes, smoking), renal insufficiency, atrial
      fibrillation/known heart failure and coronary artery calcification. RESULTS:
      Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects
      suffering stroke had significantly higher BNP values at baseline than the
      remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001].
      In a multivariable regression, log10 BNP was an independent stroke predictor
      [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in
      addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood
      pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24
      3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P =
      0.037) and computed-tomography-based log10 (coronary artery calcification + 1)
      (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women,
      both in subjects <=65 and >65 years. In subsequent analyses, BNP discriminated
      the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of
      macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367)
      origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of
      coronary calcification.

PMID- 24661835
TI  - Increase in facet joint loading after nucleotomy in the human lumbar spine.
AB  - Low-back pain has been related to degenerative changes after nucleotomy. Although
      several etiologies for pain after nucleotomy have been proposed, there is
      evidence of pain arising in the facet joints in general, which may be related to
      changes in load transfer. This study addresses the effect of nucleotomy on facet
      joint loading. Nine human lumbar motion segments (age: 40-59 years) were loaded
      in axial compression and extension-flexion. Reaction forces were compared with
      soft tissue structures sequentially removed. After nucleotomy the facets
      supported significantly greater load, almost doubling from a median of 8.6% of
      the applied external force to 15.8%. Force transmission related to the capsular
      ligament increased significantly from an intact median of 1.2-5.1% after
      nucleotomy. No correlation was observed between force increase on the facets and
      the proportion of disc nucleus removed. Even a small quantity of nucleus removal
      (range: 0.7-1.7g) increased the forces transmitted over the facet joints, both
      with and without capsular ligaments. This suggests that the proportion of
      material removed might not be important clinically with regard to facet joint
      degeneration and pain. 

PMID- 24661837
TI  - [Treatment of hepatitis C infection. A revolution should not hide another].

PMID- 24661836
TI  - Effects of whole grain rye crisp bread for breakfast on appetite and energy
      intake in a subsequent meal: two randomised controlled trails with different
      amounts of test foods and breakfast energy content.
AB  - BACKGROUND: Fibre-rich rye products have been shown to have superior effects on
      self-reported appetite compared to white wheat bread and some studies have shown
      lower energy intake after subsequent meal. The aim of the present study was to
      evaluate the effects of whole grain rye crisp bread (RB) versus refined wheat
      bread (WB) on appetite in two studies using different portion sizes and total
      energy intakes. METHODS: Two randomised cross-over pre-load studies were
      conducted in 20 and 21 subjects, respectively. Appetite was rated by visual
      analogue scale (VAS) for 4 h. In both studies, participants were 39 +/- 14 years
      old and had BMI 23 +/- 3. The studies differed in terms of energy content of the
      breakfasts and proportion of energy from the treatment product as well as amount
      of test products. Differences between treatments within the two studies were
      evaluated using mixed models with repeated measures appropriate for cross-over
      designs. RESULTS: In Study one, hunger and desire to eat were significantly lower
      (P < 0.05) after RB compared with WB, but there were no difference for fullness
      or difference in energy intake at lunch served ad libitum. In Study two, the
      portion size was lower than in Study one and the test product constituted a
      larger proportion of the breakfast. Fullness was significantly higher after RB
      compared with WB (P < 0.05) and hunger, desire to eat as well as energy intake at
      lunch were significantly lower (P < 0.05). CONCLUSIONS: Whole grain rye crisp
      bread caused lower self-reported hunger, higher fullness and less desire to eat
      compared to refined wheat bread. It also led to a lower energy intake after an ad
      libitum lunch. Results were stronger and/or more consistent when the test meal
      portion was smaller and accounted for a larger proportion of the total energy
      intake of the breakfast.

PMID- 24661838
TI  - Circulating MicroRNAs in blood of patients with prostate cancer.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are small regulatory RNAs that do not code for
      proteins. Detection of circulating tumor cells (CTC) would provide diagnostic and
      prognostic information in prostate tumors (PT). Thus, miRNAs could constitute a
      promising new class of biomarkers for CTC detection. OBJECTIVES: To analyze
      circulating microRNAs in whole blood as non-invasive markers in patients with
      localized prostate cancer and healthy individuals. MATERIAL AND METHODS: A
      preliminary study including a population of 40 patients with mean age of 71 years
      and mean PSA of 18, 9 ng/ml (range). Regarding the risk group (RG): 33.3% had low
      risk, 30% intermediate risk and 36.7% high risk. A previous in silico study
      identified 92 candidates and was followed by another in vivo to verify the
      findings of the former using array technology by real-time PCR. RESULTS:
      Statistical analysis of the results revealed 10 microRNAs candidates with
      statistically significant differential expression between the different risk
      groups and healthy controls: hsa-miR-337-3p, hsa-miR-330-3p, hsa-miR-339-3p, hsa
      miR-124, hsa-miR-218, hsa-miR-128, hsa-miR-10a, hsa-miR-199b-5p, hsa-miR-200b and
      hsa-miR-15b. CONCLUSIONS: Our data suggest that circulating microRNAs can act as
      biomarkers to identify risk groups in CaP.

PMID- 24661839
TI  - Race-ethnicity and cerebral small vessel disease--comparison between Chinese and
      White populations.
AB  - BACKGROUND AND AIM: Studies in stroke patients suggest that lacunar stroke and
      intracerebral hemorrhage might be more common in Chinese than Whites. We
      hypothesized that other manifestations of subclinical cerebral small vessel
      disease, namely white matter hyperintensities (WMH), lacunes, and microbleeds,
      are also more common in Chinese than Whites. We compared the community prevalence
      of these lesions between Han Chinese and White Australians. METHODS: Magnetic
      resonance imaging (1.5-Tesla) was performed on participants of the Shanghai Aging
      Study (n = 321, mean age 69 +/- 6 years) and Tasmanian Study of Cognition and
      Gait (n = 397, mean age 72 +/- 7 years). A single-rater recorded measures of WMH,
      lacunes, and microbleeds. We compared lesion prevalence between age- and gender
      matched subgroups from the two cohorts. Among all subjects (n = 718), we
      performed multivariable logistic regression to examine if race-ethnicity was
      independently associated with these lesions. RESULTS: Among age- and gender
      matched subjects, confluent WMH were significantly more prevalent in Chinese
      (38.5%) than Whites (28.4%; P = 0.01). There was no difference in the prevalence
      of lacunes (Chinese 29.1% vs. Whites 29.5%, P = 0.93) and microbleeds (Chinese
      10.1% vs. 9.0%, P = 0.67) between Chinese and Whites. In multivariable logistic
      regression, Chinese ethnicity was associated with confluent WMH (odds ratio 1.7,
      95% confidence interval 1.1-2.6, P = 0.01), but no differences were seen for
      lacunes and microbleeds. The association between Chinese ethnicity with confluent
      WMH became insignificant when subjects with history of stroke were excluded.
      CONCLUSIONS: In this population-based cross-national comparison, Han Chinese had
      a higher prevalence of confluent WMH than White Australians, but had a similar
      prevalence of lacunes and microbleeds.

PMID- 24661840
TI  - Paracentesis-induced inflammation: a new syndrome?

PMID- 24661842
TI  - Predictors of mortality among bacteremic patients with septic shock receiving
      appropriate antimicrobial therapy.
AB  - BACKGROUND: Factors capable of impacting hospital mortality in patients with
      septic shock remain uncertain. Our objective was to identify predictors of
      hospital mortality among patients who received appropriate antimicrobial therapy
      for bacteremic septic shock after accounting for severity of illness,
      resuscitation status, and processes of care. METHODS: We conducted a secondary
      subgroup analysis of a prospective severe sepsis cohort study. Patients with
      septic shock and positive blood cultures who received appropriate antimicrobial
      therapy were included. Univariable analyses were used to identify differences
      between hospital survivors and non-survivors, and a multivariable logistic
      regression model revealed independent determinants of hospital mortality.
      RESULTS: From January 2008 to December 2010, 58 of 224 included patients died in
      the hospital. Multivariable logistic regression analysis demonstrated 2
      independent predictors of hospital mortality. These included continuous renal
      replacement therapy utilization within 48 hours of septic shock recognition
      (adjusted odds ratio [OR], 5.52; 95% confidence interval [CI], 1.94-16.34) and
      intra-abdominal infection (adjusted OR, 3.92; 95% CI, 1.47-10.79). Escherichia
      coli was independently associated with a lower risk of hospital mortality
      (adjusted OR, 0.34; 95% CI, 0.11-0.90). CONCLUSION: Intra-abdominal infection and
      continuous renal replacement therapy were associated with increased hospital
      mortality in patients with septic shock who received appropriate antimicrobial
      therapy. Our findings may be explained by suboptimal intra-abdominal infection
      management or inadequate antimicrobial concentration in these patients.

PMID- 24661843
TI  - Effects of hydroformylation treatment on the storage time and blood group antigen
      expressions of reagent red blood cells.
AB  - OBJECTIVE: To evaluate the effects of hydroformylation treatment on the storage
      time and blood group antigen expressions of reagent red blood cells (RBCs).
      MATERIAL AND METHODS: RBCs from healthy donors were treated by using various
      final concentrations of paraformaldehyde (0.01%, 0.02%, 0.05%, 0.1%, 0.2%, 0.5%
      and 1.0%) and glutaraldehyde (0.01%, 0.025%, 0.05%, 0.1%, 0.2%, 0.5% and 1.0%),
      and one aliquot was used as control (untreated with aldehydes). Supernatant free
      hemoglobin (FHb) levels in all groups stored at 4  degrees C were detected every
      week, and the optimal procedure was selected. Expression of blood group antigens
      on RBCs treated by the optimal procedure was determined, and the total scores of
      blood group antigens were calculated. RESULTS: 0.2%, 0.5% and 1.0% Glutaraldehyde
      groups were ruled out directly due to serious crosslinking and aggregation of
      RBCs. As the extension of time, FHb levels in other 11 groups gradually increased
      (p<0.01 or p<0.05). FHb level in 0.025% glutaraldehyde group was significantly
      lower than that in other groups after 13 weeks (p<0.01), and the antigen strength
      of Fy(b), Jk(b), and Le(b) decreased slightly compared with those before
      treatment and storage (p<0.05), and there was no significant change for antigen
      strength of A, B, D, C, E, c, e, M, N, S, s, k, P1, Fy(a), Jk(a), and Le(a)
      (p>0.05). CONCLUSION: 0.025% Glutaraldehyde treatment can provide optimal
      protection for the membrane of RBCs and keep hemolysis at a low level after 13
      weeks storage, and the majority of blood group antigen systems are not
      significantly affected, and the slight decline of Fy(b), Jk(b), and Le(b) antigen
      strength was acceptable for classical serological tests.

PMID- 24661844
TI  - Citrate metabolism and its complications in non-massive blood transfusions:
      association with decompensated metabolic alkalosis+respiratory acidosis and serum
      electrolyte levels.
AB  - BACKGROUND AND OBJECTIVES: Metabolic alkalosis, which is a non-massive blood
      transfusion complication, is not reported in the literature although metabolic
      alkalosis dependent on citrate metabolism is reported to be a massive blood
      transfusion complication. The aim of this study was to investigate the effect of
      elevated carbon dioxide production due to citrate metabolism and serum
      electrolyte imbalance in patients who received frequent non-massive blood
      transfusions. MATERIALS AND METHODS: Fifteen inpatients who were diagnosed with
      different conditions and who received frequent blood transfusions (10-30
      ml/kg/day) were prospectively evaluated. Patients who had initial metabolic
      alkalosis (bicarbonate>26 mmol/l), who needed at least one intensive blood
      transfusion in one-to-three days for a period of at least 15 days, and whose
      total transfusion amount did not fit the massive blood transfusion definition
      (<80 ml/kg) were included in the study. RESULTS: The estimated mean total citrate
      administered via blood and blood products was calculated as 43.2 +/- 34.19
      mg/kg/day (a total of 647.70 mg/kg in 15 days). Decompensated metabolic
      alkalosis+respiratory acidosis developed as a result of citrate metabolism. There
      was a positive correlation between cumulative amount of citrate and the use of
      fresh frozen plasma, venous blood pH, ionized calcium, serum-blood gas sodium and
      mortality, whereas there was a negative correlation between cumulative amount of
      citrate and serum calcium levels, serum phosphorus levels and amount of urine
      chloride. CONCLUSION: In non-massive, but frequent blood transfusions, elevated
      carbon dioxide production due to citrate metabolism causes intracellular
      acidosis. As a result of intracellular acidosis compensation, decompensated
      metabolic alkalosis+respiratory acidosis and electrolyte imbalance may develop.
      This situation may contribute to the increase in mortality. In conclusion, it
      should be noted that non-massive, but frequent blood transfusions may result in
      certain complications.

PMID- 24661845
TI  - The relationship between total red blood cells and plasma transfusion and acute
      lung injury risk after cardiac surgery: a retrospective study.
AB  - The aim of our study was to determine whether red blood cells (RBCs) and fresh
      frozen plasma (FFP) transfusion is independently associated with the development
      of acute lung injury (ALI) in patients after cardiac surgery. In retrospective
      study, 165 patients were included. The results showed total fresh RBCs
      transfusion were not significantly increased in patients who developed ALI
      compared with patients who did not develop ALI (4.7 +/- 2.4, 4 [0-12] units VS
      4.0 +/- 1.9, 3 [0-9] units, P = 0.119). FFP transfusion were also not
      significantly increased (704.1 +/- 832.5, 600 [150-6500] ml VS 533.9 +/- 323.6,
      400 [125-3100] ml, P = 0.053). Multivariable logistic regression analysis showed
      that only age and CPB time were independent factors for ALI, but not for total
      RBCs and FFP transfused, with the adjusted OR 0.952 (95% CI 0.762-1.189,
      P=0.664), and 1.000 (95% CI 0.999-1.001, P = 0.480), respectively. In subgroup
      analysis, female patients showed a lower ALI incidence in low RBCs transfused
      group (23.9% VS 45.0%, OR 0.38, 95% CI 0.15-0.98) and in low FFP transfused group
      (22.0% VS 44.4%, OR 0.35, 95% CI 0.14-0.90). Our study demonstrates that red
      blood cells and fresh-frozen plasma transfusion are not related with ALI after
      cardiac surgery in our institution.

PMID- 24661846
TI  - Molecular blood grouping.

PMID- 24661847
TI  - Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent
      cyclooxygenase-2 inhibitors.
AB  - A series of thio-substituted pyrimidine, benzoxazole, benzothiazole and triazole
      analogues were synthesized from Baylis-Hillman bromides in a clean and efficient
      way. The synthesized twenty new compounds were subjected to in vitro COX-1 and
      COX-2 inhibitory activity. Majority of compounds found to be highly selective COX
      2 inhibitor. Seven compounds (16e, 16f, 16k, 16l, 16m, 16r and 16s) displayed
      anti-inflammatory activity at micromolar concentrations with IC50 values for COX
      2 inhibition ranging from 2.93 to 5.34 MUM compared to reference drug whose IC50
      is 2.66 MUM. All these seven compounds had very little COX-1 inhibition property
      and thus are suitable candidates for anti-inflammatory drugs with less
      gastrointestinal side effect.

PMID- 24661848
TI  - Lack of timely accrual information in oncology clinical trials: a cross-sectional
      analysis.
AB  - BACKGROUND: Poor accrual is a significant barrier to the successful completion of
      oncology clinical trials; half of all phase 3 oncology trials close due to
      insufficient accrual. Timely access to accrual data fosters an understanding of
      successful trial design and can be used to inform the design of new clinical
      trials prospectively. Accrual statistics are available within research networks,
      such as the cancer cooperative groups, but comprehensive data reflecting the
      overall portfolio of cancer clinical trials are lacking. As a demonstration case,
      the purpose of this study was to quantify the public availability of accrual data
      across all recent renal cell carcinoma (RCC) trials. METHODS: The database for
      the Aggregate Analysis of ClinicalTrials.gov (AACT) summarizes all trials
      registered between October 2007 and September 2010. In total, 108 trials of
      pharmacologic therapy for RCC were included. Accrual data on these trials were
      gathered via ClinicalTrials.gov (CTG), a manual review of resulting publications,
      and online surveys sent to principle investigators or trial coordinators.
      RESULTS: In total, 26% (20 of 76) of trials listing a government, academic, or
      cooperative group (GAC) sponsor responded to the survey vs 0% (0 of 32) of those
      listing only industry sponsors. Across all methods, accrual data were available
      for only 40% (43 of 108) of trials, including 37% (28 of 76) of GAC trials and
      47% (15 of 32) of industry trials. Moreover, 87% (66 of 76) of GAC trials were
      ongoing (open, actively recruiting, or of unknown status) vs 75% (24 of 32) of
      industry trials, while 9% (10 of 108) of trials were terminated or suspended.
      CONCLUSIONS: Despite extensive efforts (surveys, phone calls, CTG abstraction,
      publication searches), accurate accrual data remained inaccessible for 60% of the
      RCC trial cohort. While CTG reports trial results, ongoing accrual data are also
      critically needed. Poor access to accrual data will continue to limit attempts to
      develop a national summary of clinical trials metrics and to optimize the cancer
      clinical research portfolio.

PMID- 24661849
TI  - Prospective evaluation of the clinical utility of 18-fluorodeoxyglucose PET CT
      scanning in patients with von hippel-lindau-associated pancreatic lesions.
AB  - BACKGROUND: The natural history of pancreatic neuroendocrine neoplasms (PNENs) in
      patients with Von Hippel-Lindau (VHL) disease is poorly defined. Management of
      patients with PNENs is challenging because there are no reliable preoperative
      criteria to detect malignant lesions, and the majority of resected tumors are
      found to be benign. The aim of this study was to determine whether 18
      fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) uptake predicts
      growth and detects malignant VHL-associated PNENs. STUDY DESIGN: We performed a
      prospective study of 197 patients with VHL-associated pancreatic lesions.
      Clinical and imaging characteristics were analyzed to study the associations
      between FDG-PET uptake, tumor growth, and the development of metastatic disease.
      RESULTS: One hundred nine of 197 patients had solid pancreatic lesions and
      underwent both CT and (18)FDG-PET scanning, which identified 165 and 144 lesions,
      respectively. Metastatic disease was detected by (18)FDG-PET in 3 patients in
      whom it was not detected by CT scan and suggested non-neoplastic disease in 3
      patients. Maximum standardized uptake values (SUV) on (18)FDG-PET correlated with
      tumor size on CT (r = 0.47, p < 0.0001), and an increase in SUVmax was associated
      with tumor growth (r = 0.36, p = 0.0062). No association was seen between (18)FDG
      PET uptake and age, VHL genotype, or serum chromogranin A levels. CONCLUSIONS:
      Scanning with FDG-PET identifies metastatic disease not detected by CT scan and
      avoids resection of non-PNEN lesions that have no malignant potential in patients
      with VHL-associated PNENs. It should be considered as a valuable functional
      imaging modality in the clinical management of patients with VHL-associated
      PNENs.

PMID- 24661850
TI  - Long-term outcomes of patients with nonsurgically managed uncomplicated
      appendicitis.
AB  - BACKGROUND: Emerging literature has supported the safety of nonoperative
      management of uncomplicated appendicitis. STUDY DESIGN: Patients with emergent,
      uncomplicated appendicitis were identified by appropriate ICD-9 diagnosis codes
      in the California Office of Statewide Health Planning and Development database
      from 1997 to 2008. Rates of treatment failure, recurrence, and perforation after
      nonsurgical management were calculated. Factors associated with treatment
      failure, recurrence, and perforation were identified using multivariable logistic
      regression. Mortality, length of stay, and total charges were compared between
      treatment cohorts using matched propensity score analysis. RESULTS: Of 231,678
      patients with uncomplicated appendicitis, the majority (98.5%) were managed
      operatively. Of the 3,236 nonsurgically managed patients who survived to
      discharge without an interval appendectomy, 5.9% and 4.4% experienced treatment
      failure or recurrence, respectively, during a median follow-up of more than 7
      years. There were no mortalities associated with treatment failure or recurrence.
      The risk of perforation after discharge was approximately 3%. Using multivariable
      analysis, race and age were significantly associated with the odds of treatment
      failure. Sex, age, and hospital teaching status were significantly associated
      with the odds of recurrence. Age and hospital teaching status were significantly
      associated with the odds of perforation. Matched propensity score analysis
      indicated that after risk adjustment, mortality rates (0.1% vs 0.3%; p = 0.65)
      and total charges ($23,243 vs $24,793; p = 0.70) were not statistically different
      between operative and nonoperative patients; however, length of stay was
      significantly longer in the nonoperative treatment group (2.1 days vs 3.2 days; p
      < 0.001). CONCLUSIONS: This study suggests that nonoperative management of
      uncomplicated appendicitis can be safe and prompts additional investigations.
      Comparative effectiveness research using prospective randomized studies can be
      particularly useful.

PMID- 24661851
TI  - Are general surgery residents ready to practice? A survey of the American College
      of Surgeons Board of Governors and Young Fellows Association.
AB  - BACKGROUND: General surgery residency training has changed with adoption of the
      80-hour work week, patient expectations, and the malpractice environment,
      resulting in decreased resident autonomy during the chief resident year. There is
      considerable concern that graduating residents are not prepared for independent
      surgical practice. STUDY DESIGN: Two online surveys were developed, one for
      "young surgeons" (American College of Surgeons [ACS] Fellows 45 years of age and
      younger) and one for "older surgeons" (ACS Fellows older than 45 years of age).
      The surveys were distributed by email to 2,939 young and 9,800 older surgeons.
      The last question was open-ended with a request to provide comments. A
      qualitative and quantitative analysis of all comments was performed. RESULTS: The
      response rate was 9.6% (282 of 2,939) of young and 10% (978 of 9,800) of older
      surgeons. The majority of young surgeons (94% [58.7% strongly agree, 34.9%
      agree]) stated they had adequate surgical training and were prepared for
      transition to the surgery attending role (91% [49.6% strongly agree, 41.1%
      agree]). In contrast, considerably fewer older surgeons believed that there was
      adequate surgical training (59% [18.7% strongly agree, 40.2% agree]) or adequate
      preparation for transition to the surgery attending role (53% [16.93% strongly
      agree, 36.13% agree]). The 2 groups' responses were significantly different, chi
      square test of association (3) = 15.73, p = 0.0012. Older surgeons focused
      considerably more on residency issues (60% vs 42%, respectively), and young
      surgeons focused considerably more on business and practice issues (30% vs 14%,
      respectively). CONCLUSIONS: Young and older surgeons' perceptions of general
      surgery residents' readiness to practice independently after completion of
      general surgery residency differ significantly. Future work should focus on
      determination of specific efforts to improve the transition to independent
      surgery practice for the general surgery resident.

PMID- 24661852
TI  - Changes in colorectal cancer care in japan before and after guideline
      publication: a nationwide survey about D3 lymph node dissection and adjuvant
      chemotherapy.
AB  - BACKGROUND: The Japanese Society for Cancer of the Colon and Rectum (JSCCR)
      published clinical guidelines for the treatment of colorectal cancer (CRC) in
      2005. To evaluate the impact of these guidelines on clinical practice nationwide,
      we examined the change in the proportion of patients receiving the recommended
      CRC treatments. STUDY DESIGN: We collected treatment information on patients with
      stage II and stage III CRC who underwent surgery in participating facilities
      between 2001 and 2010. We focused on the performance of 2 treatments recommended
      by the JSCCR-guidelines: D3 lymph node dissection and postoperative adjuvant
      chemotherapy. RESULTS: The data of 46,304 patients treated in 96 institutions
      were collected. The proportion of patients receiving D3 dissection increased over
      time from 58.4% in 2001 to 75.0% in 2010. The increase accelerated after the
      publication of the JSCCR guidelines in 2005 (2.5% from 2001 to 2005 vs 14.1% from
      2005 to 2010). Similarly, the percentage of stage III patients receiving adjuvant
      chemotherapy increased over time from 50.8% in 2001 to 71.0% in 2010, but the
      increase was smaller after guideline publication (16.3% between 2001 and 2005 vs
      3.9% from 2005 to 2010). Although the performance of each of the recommended
      treatments varied substantially among institutions, the variation decreased over
      time. CONCLUSIONS: D3 dissection for stage II to III disease and adjuvant
      chemotherapy for stage III disease have become more prevalent and the variation
      in performance among institutions has decreased in the last decade. Importantly,
      publication of the guidelines has accelerated the spread of surgical standards.

PMID- 24661854
TI  - Measuring surgical quality: comparison of postoperative adverse events with the
      american college of surgeons NSQIP and the Thoracic Morbidity and Mortality
      classification system.
AB  - BACKGROUND: Monitoring surgical outcomes is critical to quality improvement;
      however, different data-collection methodologies can provide divergent
      evaluations of surgical outcomes. We compared postoperative adverse event
      reporting on the same patients using 2 classification systems: the
      retrospectively recorded American College of Surgeons (ACS) NSQIP and the
      prospectively collected Thoracic Morbidity and Mortality (TM&M) system. STUDY
      DESIGN: Using the TM&M system, complications and deaths were documented daily by
      fellows and reviewed weekly by staff for all thoracic surgical cases conducted at
      our institution (April 1, 2010 to December 31, 2011). The ACS NSQIP recording was
      performed 30 to 120 days after index surgery by trained surgical clinical
      reviewers on a systemic sampling of major cases during the same time period.
      Univariate analyses of the data were performed. RESULTS: During the study period,
      1,788 thoracic procedures were performed (1,091 were designated "major," as per
      ACS NSQIP inclusion criteria). The ACS NSQIP evaluated 182 of these procedures,
      representing 21.1% and 16.7% of patients and procedures, respectively. Mortality
      rates were 1.4% in TM&M vs 2.2% in ACS NSQIP (p = 0.42). Total patients and
      procedures with complications reported were 24.4% and 31.1% by TM&M vs 20.2% and
      39.0% by ACS NSQIP (p = 0.23 and 0.03), respectively. Rates of reported cardiac
      complications were higher in TM&M vs ACS NSQIP (5.8% vs 1.1%; p = 0.01), and
      wound complications were lower (2.5% vs 6.0%; p = 0.01). CONCLUSIONS: Although
      overall rates were similar, significant differences in collection, definitions,
      and classification of postoperative adverse events were observed when comparing
      TM&M and ACS NSQIP. Although both systems offer complementary value,
      harmonization of definitions and severity classification would enhance quality
      improvement programs.

PMID- 24661853
TI  - The effect of medicaid expansion in new york state on use of subspecialty
      surgical procedures by medicaid beneficiaries and the uninsured.
AB  - BACKGROUND: Understanding the benefits of Medicaid is crucial as states decide
      whether to expand Medicaid under the Patient Protection and Affordable Care Act.
      We used the 2001 Medicaid expansion in New York to evaluate changes in use by
      Medicaid beneficiaries and the uninsured of breast cancer reconstruction,
      panniculectomy, and lower-extremity trauma management. METHODS: Data for all
      patients 19 to 64 years old having undergone the selected procedures between 1998
      and 2006 were obtained from the State Inpatient Database. We used an interrupted
      time series using variance weighted least squares regression to evaluate the
      effect of Medicaid expansion on the probability that Medicaid beneficiaries or
      uninsured patients received the procedures. We also determined the predicted use
      had there been no expansion. New York Census data were used for population
      adjusted case-volume calculations. RESULTS: Likelihood of Medicaid as the primary
      payer increased significantly after expansion, 0.34% per quarter (95% CI, 0.28
      0.40), without a decrease in uninsured patients receiving these procedures. This
      resulted in a 7.2% increase in the proportion of Medicaid beneficiaries receiving
      these procedures, an additional 1.9 Medicaid cases per quarter per 100,000 New
      York residents. In subgroup analysis, the proportion of Medicaid beneficiaries
      increased for breast reconstruction (0.28% per quarter; 95% CI, 0.21-0.35) and
      panniculectomy (0.19% per quarter; 95% CI, 0.1-0.28) without a decrease for the
      uninsured. Lower-extremity trauma procedures had a decreasing trend in use by
      uninsured patients with a slight increase for Medicaid beneficiaries (not
      significant). CONCLUSIONS: Subspecialty surgeons responded to expansion by
      increasing volume of procedures for Medicaid beneficiaries. This occurred without
      decline in care for the uninsured, suggesting that Medicaid expansion resulted in
      increased access for underserved patients. Although more patients received needed
      care once they had coverage, subgroup analysis identified persistence of
      additional barriers to use of certain surgical services.

PMID- 24661855
TI  - Timing of complications and length of stay after rectal cancer surgery.
AB  - BACKGROUND: Enhanced recovery pathways have been shown to improve short-term
      outcomes after colorectal surgery. Occurrence of complications can lead to
      prolonged length of stay (LOS). The goal of this study was to examine whether
      shorter time to occurrence of complications was associated with a shorter
      hospital LOS in rectal cancer patients undergoing minimally invasive surgery,
      taking into account the perioperative pathway. STUDY DESIGN: This retrospective
      study included consecutive patients undergoing rectal cancer resection from 2005
      to 2011 at a single institution. Enhanced recovery pathway was introduced in
      2009. Complications and date of occurrence were reviewed. The impact of
      perioperative care modalities and comorbidities was evaluated using competing
      risk models with occurrence of complications and LOS as time-dependent outcomes
      measured as time from surgery. RESULTS: A total of 346 patients were included in
      the analysis with 78 patients treated with enhanced recovery pathway, and 268
      with established care. The overall complication rate was 22.3% (77 patients with
      ileus, wound infection, leak, abscess, small bowel obstruction, reoperation for
      bleeding, and renal failure). Median time to occurrence of a complication was 3
      days post operation. The time to complication diagnosis was associated with
      shorter time to discharge after the advent of the complication (hazard ratio =
      0.84; 95% CI, 0.73-0.96; p = 0.01). Enhanced recovery pathway was associated with
      a shorter LOS for patients without complications compared with the established
      pathway (hazard ratio = 2.81; 95% CI, 2.09-3.78; p < 0.001) after adjusting for
      comorbidities in a competing risk model. CONCLUSIONS: Early diagnosis of
      postoperative complications is associated with a shorter LOS after rectal cancer
      surgery. Enhanced recovery pathway can facilitate a faster recovery in the
      presence of comorbidities.

PMID- 24661856
TI  - Increasing the number of lymph nodes examined after colectomy does not improve
      colon cancer staging.
AB  - BACKGROUND: Current quality initiatives call for examination of at least 12 lymph
      nodes in curative colon cancer resections. The aim of this study was to determine
      if the number of nodes harvested has increased, and if the increased number nodes
      correlates with improved staging or overall survival. STUDY DESIGN: A review of
      the Surveillance, Epidemiology, and End Results program database from 2004-2010
      was performed. All patients who underwent colon cancer resection during this date
      range were analyzed. Number of nodes retrieved, patient stage, overall survival,
      and overall survival by stage were examined. Multivariable analysis controlled
      for stage, cancer site, age, year of diagnosis, and number of nodes retrieved.
      Improved staging was defined as increased detection of stage III patients.
      RESULTS: A total of 147,076 patients met inclusion criteria. Median number of
      nodes analyzed increased sequentially with each year examined, from 12 in 2004 to
      17 in 2010. Despite greater number of total nodes obtained and analyzed, there
      was no increase in the percentage of patients with positive nodes (stage III
      disease). On multivariable analysis, after controlling for stage, site of
      disease, age, and year of diagnosis, there was a slight overall survival benefit
      with increasing nodal retrieval (hazard ratio = 0.987 for each additional node
      removed; 95% CI, 0.986-0.988; p < 0.001). CONCLUSIONS: Since quality initiatives
      have been put in place, there has been an increase in the number of nodes
      examined in colon cancer resections, but no improvement in staging. The improved
      survival seen with higher node counts was independent of stage, site of disease,
      patient age, and year of diagnosis.

PMID- 24661857
TI  - Endovascular stenting is rarely necessary for the management of blunt
      cerebrovascular injuries.
AB  - BACKGROUND: The role of stenting for blunt cerebrovascular injuries (BCVI)
      continues to be debated, with a trend toward more endovascular stenting. With the
      recent intracranial stenting trial halted in favor of medical therapy, however,
      management of BCVI warrants reassessment. The study purpose was to determine if
      antithrombotic therapy, rather than stenting, was effective in post-injury
      patients with high-grade vascular dissections and pseudoaneurysms. STUDY DESIGN:
      In 1996, we began screening for BCVI. After the 2005 report on the risks of
      carotid stenting for BCVI, a virtual moratorium was placed on stenting at our
      institution; our primary therapy for BCVI has been antithrombotics. Patients with
      grade II (luminal narrowing >25%) and grade III (pseudoaneurysms) injuries were
      included in the analysis. RESULTS: Grade II or III BCVIs were diagnosed in 195
      patients. Before 2005, 25% (21 of 86) of patients underwent stent placement, with
      2 patients suffering stroke. Of patients treated with antithrombotics, 1 had a
      stroke. After 2005, only 2% (2 of 109) of patients with high-grade injuries had
      stents placed. After 2005, no patient treated with antithrombotics suffered a
      stroke and there was no rupture of a pseudoaneurysm. CONCLUSIONS: Antithrombotic
      treatment for BCVI is effective for stroke prevention. Routine stenting entails
      increased costs and potential risk for stroke, and does not appear to provide
      additional benefit. Intravascular stents should be reserved for the rare patient
      with symptomatology or a markedly enlarging pseudoaneurysm.

PMID- 24661858
TI  - Enantioseparation of chiral pharmaceuticals in biomedical and environmental
      analyses by liquid chromatography: an overview.
AB  - This review aims to present the issues associated to enantioseparation of chiral
      pharmaceuticals in biological and environmental matrices using chiral stationary
      phases (CSP). Thus, it related some enantioselective methods in liquid
      chromatography (LC) and compares the importance given to chiral separation in
      biomedical and environmental fields. For that the most used CSP, the
      enantioselective chromatographic methods, their advantages and drawbacks were
      swiftly revised and compared. The recent advances and the limitations of chiral
      analytical methods in LC were also discussed. 

PMID- 24661859
TI  - Cortical necrosis in a kidney transplant recipient due to leptospirosis.

PMID- 24661860
TI  - Sildenafil overdose can cause rhabdomyolysis and subjective visual perception
      changes.

PMID- 24661861
TI  - Simple renal cyst and hypertension: an often neglected entity.

PMID- 24661862
TI  - Prevalence, racial variations, and risk factors of age-related macular
      degeneration in Singaporean Chinese, Indians, and Malays.
AB  - OBJECTIVE: To describe the prevalence and risk factors for age-related macular
      degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian
      persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of
      10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40
      years of age or older residing in Singapore. METHODS: We performed comprehensive
      systemic and ocular examinations, retinal photography, and laboratory
      investigations for all participants. We graded early and late AMD signs from
      retinal photographs using the modified Wisconsin AMD grading scale. We calculated
      the age-standardized prevalence of AMD using the 2010 Singapore adult population
      and analyzed risk factors for AMD using logistic regression models. MAIN OUTCOME
      MEASURES: Early and late AMD. RESULTS: Of the 9799 participants with gradable
      photographs, 588 had early AMD and 60 had late AMD. The age-standardized
      prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and
      0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar
      between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays
      (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in
      contrast, the prevalence for late AMD was similar across ethnic groups (Chinese,
      0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were
      older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47),
      male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02
      1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical
      equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR,
      1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs
      per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease
      (OR, 2.17; 95% CI, 1.22-3.88). CONCLUSIONS: Early AMD is more common in Chinese
      and Indians than in Malays, but there were no racial variations in the prevalence
      of late AMD.

PMID- 24661863
TI  - Low-luminance visual acuity and microperimetry in age-related macular
      degeneration.
AB  - OBJECTIVE: To compare the effectiveness of low-luminance visual acuity (LLVA) and
      microperimetry as functional measures in early stages of age-related macular
      degeneration (AMD). DESIGN: Prospective cross-sectional study. PARTICIPANTS: One
      hundred seventy-nine participants with a clinical spectrum of non-neovascular AMD
      and 26 control participants. METHODS: Best-corrected visual acuity (BVCA), LLVA,
      and microperimetric retinal sensitivity were measured on 1 eye of all
      participants. Low-luminance deficit (LLD) was calculated as the difference
      between LLVA and BCVA. The functional parameters were compared between 6 clinical
      severity groups (from controls to non-foveal geographic atrophy [GA]), and the
      relationships and magnitude of these parameters were determined and compared.
      MAIN OUTCOME MEASURES: Visual acuity parameters (BCVA, LLVA, and LLD) and central
      retinal sensitivity. RESULTS: Best-corrected visual acuity, LLVA, and central
      retinal sensitivity were reduced significantly for all AMD clinical severity
      groups when compared with control participants (P <= 0.002), except for those
      with drusen between 63 and 125 MUm (P >= 0.107). However, LLD was not
      significantly different from control participants in all groups (P >= 0.073),
      except in the non-foveal GA group (P = 0.008). A significant positive
      relationship between central retinal sensitivity and LLD (R = 0.613; P < 0.001),
      but not BCVA, suggests that there is a trend for LLVA to detect a greater extent
      of functional deficit than BCVA in eyes with increasingly poorer retinal
      sensitivity. However, the results of the linear regression models estimated
      central retinal sensitivity to be 6.1, 3.7, and 5.1 standard deviations (SDs)
      less than normal by the time BCVA, LLVA, and LLD, respectively, were 2 SDs less
      than normal. CONCLUSIONS: In early stages of AMD, LLVA did not detect a greater
      extent of functional deficit than BCVA when compared with control participants.
      Although there was a trend for LLVA to be more effective at detecting foveal
      deficits than BCVA in eyes with increasingly poorer retinal sensitivity, both
      visual acuity measures were much less sensitive compared with microperimetry.

PMID- 24661864
TI  - Stellate nonhereditary idiopathic foveomacular retinoschisis.
AB  - PURPOSE: To describe a new classification of stellate nonhereditary idiopathic
      foveomacular retinoschisis (SNIFR). DESIGN: Retrospective case series and
      literature review. PARTICIPANTS: A total of 17 patients from 5 institutions.
      METHODS: Detailed case history, multimodal imaging, and genetic testing were
      reviewed for patients with macular schisis without a known predisposing
      condition. Patients with a stellate appearance centered on the fovea with
      correlating confirmed expansion of the outer plexiform layer (OPL) by optical
      coherence tomography (OCT) were included. Exclusion criteria included a family
      history of macular retinoschisis, a known genetic abnormality associated with
      retinoschisis, myopic traction maculopathy, epiretinal membrane, vitreoretinal
      traction, optic or scleral pit, or advanced glaucomatous optic nerve changes.
      MAIN OUTCOME MEASURES: Clinical features, anatomic characteristics, and visual
      acuity. RESULTS: A total of 22 eyes from 16 female patients and 1 male patient
      with foveomacular schisis were reviewed from 5 institutions. Initial visual
      acuity was >= 20/50 in all eyes (mean, 20/27), but visual acuity in a single eye
      decreased from 20/20 to 20/200 after the development of subfoveal fluid. The
      refractive status was myopic in 16 eyes, plano in 3 eyes, and hyperopic in 2
      eyes. Three eyes had a preexisting vitreous separation, and 19 eyes had an
      attached posterior hyaloid. Follow-up ranged from 6 months to >5 years.
      CONCLUSIONS: In this largest known series of patients with SNIFR, all patients
      demonstrated splitting of the OPL in the macula with relatively preserved visual
      acuity (>= 20/40) except in a single patient in whom subretinal fluid developed
      under the fovea.

PMID- 24661866
TI  - Fast identification of selective resins for removal of genotoxic aminopyridine
      impurities via screening of molecularly imprinted polymer libraries.
AB  - This study describes the identification and evaluation of molecularly imprinted
      polymers (MIPs) for the selective removal of potentially genotoxic aminopyridine
      impurities from pharmaceuticals. Screening experiments were performed using
      existing MIP resin libraries to identify resins selective towards those
      impurities in the presence of model pharmaceutical compounds. A hit resin with a
      considerable imprinting effect was found in the screening and upon further
      investigation, the resin was found to show a broad selectivity towards five
      different aminopyridines in the presence of the two model active pharmaceutical
      ingredients (APIs) piroxicam and tenoxicam. 

PMID- 24661865
TI  - Phylodynamics of vampire bat-transmitted rabies in Argentina.
AB  - Common vampire bat populations distributed from Mexico to Argentina are important
      rabies reservoir hosts in Latin America. The aim of this work was to analyse the
      population structure of the rabies virus (RABV) variants associated with vampire
      bats in the Americas and to study their phylodynamic pattern within Argentina.
      The phylogenetic analysis based on all available vampire bat-related N gene
      sequences showed both a geographical and a temporal structure. The two largest
      groups of RABV variants from Argentina were isolated from northwestern Argentina
      and from the central western zone of northeastern Argentina, corresponding to
      livestock areas with different climatic, topographic and biogeographical
      conditions, which determined their dissemination and evolutionary patterns. In
      addition, multiple introductions of the infection into Argentina, possibly from
      Brazil, were detected. The phylodynamic analysis suggests that RABV transmission
      dynamics is characterized by initial epizootic waves followed by local enzootic
      cycles with variable persistence. Anthropogenic interventions in the ecosystem
      should be assessed taking into account not only the environmental impact but also
      the potential risk of disease spreading through dissemination of current RABV
      lineages or the emergence of novel ones associated with vampire bats. 

PMID- 24661867
TI  - Enantiomer separations of basic chiral compounds by capillary
      electrochromatography on a phosphated beta-cyclodextrin-modified zirconia
      monolith.
AB  - Phosphated beta-cyclodextrin (PCD)-coated zirconia monolith was used as the
      chiral stationary phase in capillary electrochromatography (CEC) for separation
      of four basic chiral compounds including metoprolol (MET), sertraline (SER),
      citalopram (CIT) and atenolol (ATE). Migration, chiral selectivity and resolution
      data were measured in reversed-phase mobile phases of varying pH, buffer and
      organic modifier compositions. Optimum mobile phase conditions for CEC separation
      of the compounds studied were found to be a 15-mM aqueous buffer of pH 5.0 with
      5mM PCD. Baseline separations of enantiomers of CIT, MET and SER, and partial
      separation for ATE were achieved with the optimal mobile phase. 

PMID- 24661868
TI  - Study on antidiabetic activity of wheat and barley starch using asymmetrical flow
      field-flow fractionation coupled with multiangle light scattering.
AB  - The ability of asymmetrical flow field-flow fractionation (AF4) coupled online
      with multiangle light scattering (MALS) and refractive index detector (RI) (AF4
      MALS-RI) for monitoring of change in molecular conformation of wheat and barley
      starch during germination process was evaluated. AF4 provides separation of
      starch molecules based on their hydrodynamic sizes, and MALS yields the molar
      mass and molecular size (radius of gyration, Rg). In vitro and in vivo anti
      hyperglycemic effect of germinated wheat and barley was studied. The relationship
      between antidiabetic activity and molecular conformation was, for the first time,
      investigated. The ratio of Rg to the hydrodynamic radius (Rh) and the apparent
      density were proven to be important parameters as they offer an insight into
      molecular conformation. Results showed that, when geminated, the apparent density
      and the antidiabetic activity of barley were significantly increased, suggesting
      germination makes the molecules more compact which could contribute to
      enhancement of their antidiabetic activity. The information obtained by AF4-MALS
      RI is valuable for understanding of germination mechanism, and thus for
      developing functional foods.

PMID- 24661870
TI  - Three-port operation in three-zone simulated moving bed chromatography.
AB  - A new operating method, namely three-port operation in a three-zone simulated
      moving bed (TT-SMB), was developed to improve the separation performance of
      simulated moving bed (SMB) chromatography. In the TT-SMB, the switching period
      consists of two steps; extract outlet port is closed at the first step for
      raffinate production and raffinate outlet port is closed at the second step for
      extract production. As a result, three ports were used in each step of the three
      zone SMB operation. The separation performance of TT-SMB was compared with
      conventional three- and four-zone SMBs in terms of purity, recovery,
      productivity, and eluent consumption. A conventional three-zone SMB operation
      usually produced the contaminated portion at the product outlet node during the
      switching period. However, such phenomenon could be prevented by using the TT-SMB
      operation because one product outlet port was closed at each step. Compared to
      the conventional three-zone SMB, all performance parameters improved with the use
      of TT-SMB, and the improvement in purity and recovery was significant (up to 7%).
      Adjusting the step ratio played a key role in the trade-off between the
      performance parameters. The purity, recovery, and productivity of TT-SMB at well
      designed step ratio conditions are up to 3% higher than those of the conventional
      four-zone methods (1-1-1-1 configuration).

PMID- 24661869
TI  - A novel strategy for the purification of a recombinant protein using ceramic
      fluorapatite-binding peptides as affinity tags.
AB  - In recent years, affinity fusion-tag systems have become a popular technique for
      the purification of recombinant proteins from crude extracts. However, several
      drawbacks including the high expense and low stability of ligands, their leakage
      during operation, and difficulties in immobilization, make it important to
      further develop the method. The present work is concerned with the utilization of
      a ceramic fluorapatite (CFT)-based chromatographic matrix to overcome these
      drawbacks. A heptapeptide library exhibiting a range of properties have been
      synthesized and subjected to ceramic fluorapatite (CFT) chromatography to
      characterize their retention behavior as a function of pH and composition of the
      binding buffer. The specific binding and elution behavior demonstrates the
      possible application of CFT-binding peptides as tags for enhancing the selective
      recovery of proteins by CFT chromatography. To materialize this strategy, a phage
      derived CFT-specific sequence KPRSVSG (Tag1) with/without a consecutive
      hexalysine sequence, KKKKKKKPRSVSG (Tag2), were fused at the C-terminus of an
      enhanced green fluorescent protein (eGFP). The resulting gene constructs H-eGFP,
      H-eGFP-Tag1 and H-eGFP-Tag2 were expressed in Escherichia coli strain BL-21, and
      the clarified cell lysate was applied to the CFT column equilibrated with binding
      buffer (20-50mM sodium phosphate, pH 6-8.4). Sodium phosphate (500mM) or 1M NaCl
      in the respective binding buffer was used to elute the fused proteins, and the
      chromatographic fractions were analyzed by gel electrophoresis. Both the yield
      and purity were over 90%, demonstrating the potential application of the present
      strategy. 

PMID- 24661871
TI  - Nonspecific interactions of chromatin with immunoglobulin G and protein A, and
      their impact on purification performance.
AB  - Chromatin released from dead host cells during in vitro production of IgG
      monoclonal antibodies exists mostly in complex hetero-aggregates consisting of
      nucleosomal arrays (DNA+histone proteins), non-histone proteins, and aberrant
      forms of IgG. They bind immobilized protein A more aggressively than IgG, through
      their nucleosomal histone components, and hinder access of IgG to Fc-specific
      binding sites, thereby reducing dynamic binding capacity. The majority of host
      cell contaminants in eluted IgG are leachates from chromatin hetero-aggregates
      that remain bound to protein A. Formation of turbidity in eluted IgG during pH
      titration is caused by neutral-pH insolubility of chromatin hetero-aggregates.
      NaOH is required at 500 mM to remove accumulated chromatin. A chromatin-directed
      clarification method removed 99% of histones, 90% of non-histone proteins,
      achieved a 6 log reduction of DNA, 4 log reduction of lipid-enveloped virus, and
      5 log reduction of non-enveloped retrovirus, while conserving 98% of the native
      IgG. This suspended most of performance compromises imposed on protein A. IgG
      binding capacity increased ~20%. Host protein contamination was reduced about 100
      fold compared to protein A loaded with harvest clarified by centrifugation and
      microfiltration. Aggregates were reduced to less than 0.05%. Turbidity of eluted
      IgG upon pH neutralization was nearly eliminated. Column cleaning was facilitated
      by minimizing the accumulation of chromatin.

PMID- 24661872
TI  - Development of a multi-preservative method based on solid-phase microextraction
      gas chromatography-tandem mass spectrometry for cosmetic analysis.
AB  - A simple methodology based on solid-phase microextraction (SPME) followed by gas
      chromatography-tandem mass spectrometry (GC-MS/MS) has been developed for the
      simultaneous analysis of different classes of preservatives including benzoates,
      bronidox, 2-phenoxyethanol, parabens, BHA, BHT and triclosan in cosmetic
      products. In situ acetylation and subsequent organic modifier addition have been
      successfully implemented in the SPME process as an effective extractive strategy
      for matrix effect compensation and chromatographic performance improvement. Main
      factors affecting SPME procedure such as fiber coating, sampling mode, extraction
      temperature and salt addition (NaCl) were evaluated by means of a 3*2(3-1)
      factorial experimental design. The optimal experimental conditions were
      established as follows: direct solid-phase microextraction (SPME) at 40 degrees C
      and addition of NaCl (20%, w/v), using a DVB/CAR/PDMS fiber coating. Due to the
      complexity of the studied matrices, method performance was evaluated in a
      representative variety of both rinse-off and leave-on samples, demonstrating to
      have a broad linear range (R(2)>0.9964). In general, quantitative recoveries
      (>85% in most cases) and satisfactory precision (RSD<13% for most of compounds)
      were obtained, with limits of detection (LODs) well below the maximum authorized
      concentrations established by the European legislation. One of the most important
      achievements of this work was the use of external calibration with cosmetic
      matched standards to accurately quantify the target analytes. The validated
      methodology was successfully applied to the analysis of different types of
      cosmetic formulations including body milks, moisturizing creams, deodorants,
      sunscreen, bath gel, dental cream and make-up products amongst others,
      demonstrating to be a reliable multi-preservative methododology for routine
      control. 

PMID- 24661873
TI  - C-Terminus of Hsc70-interacting protein regulates profilin1 and breast cancer
      cell migration.
AB  - Profilin1 (Pfn1) is a key mediator of actin polymerization and regulates cell
      migration. Low expression of Pfn1 is implicated in tumorigenesis of various
      cancers, including breast cancer. The regulatory mechanism behind Pfn1 levels has
      not yet been elucidated. In the present study, we find that Pfn1 is poly
      ubiquitinated in human cell lines, and a portion of poly-ubiquitinated Pfn1 is
      regulated in a proteasome-dependent manner. C-terminus of Hsc70-interacting
      protein (CHIP), a co-chaperone E3 ligase, interacts with and ubiquitinates Pfn1,
      targeting it for proteasome-dependent degradation. Depletion of CHIP stabilizes
      Pfn1, suggesting that CHIP functions as a major E3 ligase for Pfn1. Stable
      expression of wild-type CHIP in the breast cancer cell line MDA-MB231 yielded
      downregulation of Pfn1 and enhanced cell migration. Pfn1 overexpression in MDA
      MB231 cells expressing wild-type CHIP suppressed the enhanced cell migration.
      Taken together, our results demonstrate that CHIP regulates Pfn1 levels as an E3
      ligase, and possibly plays a role in cell migration and metastasis of breast
      cancer. 

PMID- 24661874
TI  - Tolerance induction between two different strains of parental mice prevents graft
      versus-host disease in haploidentical hematopoietic stem cell transplantation to
      F1 mice.
AB  - Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been
      employed worldwide in recent years and led to favorable outcome in a group of
      patients who do not have human leukocyte antigen (HLA)-matched donors. However,
      the high incidence of severe graft-versus-host disease (GVHD) is a major problem
      for Haplo-HSCT. In the current study, we performed a proof of concept mouse study
      to test whether induction of allogeneic tolerance between two different parental
      strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced
      alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated
      immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow
      cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice
      (C3H*Balb/c). The results demonstrated that this approach markedly reduced GVHD
      associated death and significantly prolonged the survival of recipient mice in
      contrast to the groups with donors (C3H mice) that received infusion of non-UVB
      irradiated DCs. Further studies showed that there were enhanced Tregs in the
      tolerant mice and alloantigen-specific T cell response was skewed to more IL-10
      producing T cells, suggesting that these regulatory T cells might have
      contributed to the attenuation of GVHD. This study suggests that it is a feasible
      approach to preventing GVHD in Haplo-HSCT in children by pre-induction of
      alloantigen tolerance between the two parents. This concept may also lead to more
      opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT. 

PMID- 24661875
TI  - Insights into structural features determining odorant affinities to honey bee
      odorant binding protein 14.
AB  - Molecular interactions between odorants and odorant binding proteins (OBPs) are
      of major importance for understanding the principles of selectivity of OBPs
      towards the wide range of semiochemicals. It is largely unknown on a structural
      basis, how an OBP binds and discriminates between odorant molecules. Here we
      examine this aspect in greater detail by comparing the C-minus OBP14 of the honey
      bee (Apis mellifera L.) to a mutant form of the protein that comprises the third
      disulfide bond lacking in C-minus OBPs. Affinities of structurally analogous
      odorants featuring an aromatic phenol group with different side chains were
      assessed based on changes of the thermal stability of the protein upon odorant
      binding monitored by circular dichroism spectroscopy. Our results indicate a
      tendency that odorants show higher affinity to the wild-type OBP suggesting that
      the introduced rigidity in the mutant protein has a negative effect on odorant
      binding. Furthermore, we show that OBP14 stability is very sensitive to the
      position and type of functional groups in the odorant. 

PMID- 24661876
TI  - TMEM16A alternative splicing isoforms in Xenopus tropicalis: distribution and
      functional properties.
AB  - Oocytes of Xenopus tropicalis elicit a Ca(2+)-dependent outwardly rectifying, low
      activating current (ICl,Ca) that is inhibited by Cl(-) channel blockers. When
      inactivated, ICl,Ca shows an exponentially decaying tail current that is related
      to currents generated by TMEM16A ion channels. Accordingly, RT-PCR revealed the
      expression of five alternatively spliced isoforms of TMEM16A in oocytes, which,
      after expression in HEK-293 cells, gave rise to fully functional Cl(-) channels.
      Upon hyperpolarization to -80 mV a transient current was observed only in
      isoforms that carry the exon 1d, coding for two potentially phosphorylatable
      Threonine residues. The identified isoforms are differentially expressed in
      several tissues of the frog. Thus, it appears that X. tropicalis oocytes express
      TMEM16A that gives rise to a Ca(2+)-dependent Cl(-) current, which is different
      from the previously reported voltage-dependent outwardly rectifying Cl(-)
      current.

PMID- 24661877
TI  - The type II Ca2+/calmodulin-dependent protein kinases are involved in the
      regulation of cell wall integrity and oxidative stress response in Candida
      albicans.
AB  - The type II Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are thought to
      play a vital role in cellular regulation in mammalian cells. Two genes CMK1 and
      CMK2 in the Candida albicans genome encode homologues of mammalian CaMKs. In this
      work, we constructed the cmk1Delta/Delta, the cmk2Delta/Delta and the
      cmk1Delta/Deltacmk2Delta/Delta mutants and found that CaMKs function in cell wall
      integrity (CWI) and cellular redox regulation. Loss of either CMK1 or CMK2, or
      both resulted in increased expression of CWI-related genes under Calcofluor white
      (CFW) treatment. Besides, CaMKs are essential for the maintenance of cellular
      redox balance. Disruption of either CMK1 or CMK2, or both not only led to a
      significant increase of intracellular ROS levels, but also led to a decrease of
      the mitochondrial membrane potential (MMP), suggesting the important roles that
      CaMKs play in the maintenance of the mitochondrial function. 

PMID- 24661878
TI  - Functional expression of P2X family receptors in macrophages is affected by
      microenvironment in mouse T cell acute lymphoblastic leukemia.
AB  - Nucleotides are important players in intercellular signaling communication
      network. P2X family receptors (P2XRs) are ATP-gated plasma membrane ion channels
      with diverse biological functions. Macrophages are important components in the
      microenvironment of hematopoiesis participating in both physiological and
      pathological processes. However, the role of P2XRs in macrophages in leukemia has
      not been established. Here we investigated expression pattern and functions of
      P2XRs in macrophages from bone marrow (BM) and spleen of Notch1-induced T-ALL
      mice. Real-time PCR showed that P2XRs except P2X5R were expressed in BM and
      spleen macrophages. Furthermore, with the development of leukemia, the expression
      of P2X7R increased in both BM and spleen macrophages whereas expression of P2X1R
      increased in spleen macrophages. Live cell imaging recoding the Ca(2+) response
      demonstrated that P2X7R expressed in macrophages was functional. TUNEL and
      electron microscopy analysis found that apoptotic macrophages were frequently
      observed in BM and spleen at late stage of leukemia, which was partly contributed
      by the activation of overexpressed P2X7R. Our results suggested that the
      intercellular communication mediated by nucleotides might orchestrate in the
      pathological process of leukemia and could be a potential target for the
      treatment of leukemia. 

PMID- 24661879
TI  - USF-1 inhibition protects against oxygen-and-glucose-deprivation-induced
      apoptosis via the downregulation of miR-132 in HepG2 cells.
AB  - Upstream stimulatory factor 1 (USF-1) is an important transcription factor that
      participates in glucose metabolism and tumorigenesis. The aim of the current
      study was to explore the regulatory mechanism of USF-1 in HepG2 cells exposed to
      oxygen and glucose deprivation (OGD). After the establishment of the OGD model in
      HepG2 cells, we determined that the cells treated with OGD exhibited a high
      apoptotic rate and that the introduction of siRNA against USF-1 protected the
      cells from OGD-induced apoptosis. The miRNA microarray results demonstrated that
      a set of miRNAs were deregulated in the cells transfected with USF-1 siRNA, and
      the set of downregulated miRNAs included a novel miRNA, miR-132. Further analyses
      indicated that miR-132 overexpression inhibits the protective roles of USF-1
      siRNA in OGD-induced apoptosis. We also identified several binding sites for USF
      1 in the miR-132 promoter. The silencing of USF-1 resulted in a reduction in miR
      132 expression, and USF-1 overexpression increased the expression of this miRNA.
      Our study indicated that the silencing of USF-1 plays protective roles in OGD
      induced apoptosis through the downregulation of miR-132, which indicates that the
      silencing of USF-1 may be a therapeutic strategy for the promotion of cancer cell
      survival under OGD conditions. 

PMID- 24661880
TI  - A mouse model of mitochondrial complex III dysfunction induced by myxothiazol.
AB  - Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the
      ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol
      to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool
      in studies of respiratory chain function in in vitro and cell culture models. We
      developed a mouse model of biochemically induced and reversible CIII inhibition
      using myxothiazol. We administered myxothiazol intraperitoneally at a dose of
      0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology,
      lipid content, supercomplex formation, and gene expression in the livers of the
      mice. A reversible CIII activity decrease to 50% of control value occurred at 2 h
      post-injection. At 74 h only minor histological changes in the liver were found,
      supercomplex formation was preserved and no significant changes in the expression
      of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol
      induced CIII inhibition can be induced in mice for four days in a row without
      overt hepatotoxicity or lethality. This model could be utilized in further
      studies of respiratory chain function and pharmacological approaches to
      mitochondrial hepatopathies.

PMID- 24661881
TI  - Excision of 5-hydroxymethylcytosine by DEMETER family DNA glycosylases.
AB  - In plants and animals, 5-methylcytosine (5mC) serves as an epigenetic mark to
      repress gene expression, playing critical roles for cellular differentiation and
      transposon silencing. Mammals also have 5-hydroxymethylcytosine (5hmC), resulting
      from hydroxylation of 5mC by TET family-enzymes. 5hmC is abundant in mouse
      Purkinje neurons and embryonic stem cells, and regarded as an important
      intermediate for active DNA demethylation in mammals. However, the presence of
      5hmC in plants has not been clearly demonstrated. In Arabidopsis, the DEMETER
      (DME) family DNA glycosylases efficiently remove 5mC, which results in DNA
      demethylation and transcriptional activation of target genes. Here we show that
      DME and ROS1 have a significant 5hmC excision activity in vitro, although we
      detected no 5hmC in Arabidopsis, suggesting that it is very unlikely for plants
      to utilize 5hmC as a DNA demethylation intermediate. Our results indicate that
      both plants and animals have 5mC in common but DNA demethylation systems have
      independently evolved with distinct mechanisms. 

PMID- 24661882
TI  - Allele-mining of rice blast resistance genes at AC134922 locus.
AB  - The AC134922 locus is one of the most rapidly evolving nucleotide binding site
      leucine-rich repeat (NBS-LRR) gene family in rice genome. Six rice blast
      resistance (R) genes have been cloned from this locus and other two resistance
      candidate genes, Pi34 and Pi47, are also mapped to this complex locus. Therefore,
      it seems that more functional R genes could be identified from this locus. In
      this study, we cloned 22 genes from 12 cultivars based on allele-mining strategy
      at this locus and identified 6 rice blast R genes with 4 of them recognizing more
      than one isolates. Our result suggests that gene stacking might be the
      evolutionary strategy for complex gene locus to interact with rapidly evolving
      pathogens, which might provide a potential way for the cloning of durable
      resistance genes. Moreover, the mosaic structure and ambiguous ortholog/paralog
      relationships of these homologous genes, caused by frequent recombination and
      gene conversion, indicate that multiple alleles of this complex locus may serve
      as a reservoir for the evolutionary novelty of these R genes. 

PMID- 24661883
TI  - Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics
      and analysis.
AB  - Bladder cancer is clinically characterized by high recurrent rate and poor
      prognosis and thereby patients need regular re-examinations which are invasive,
      unpleasant, and expensive. A noninvasive and less expensive method for detecting
      and monitoring bladder cancer would thus be advantageous. In this study, by using
      the two-dimensional electrophoresis (2-DE) approach with subsequent mass
      spectrometry (MS), we demonstrated the increased expression of apolipoprotein-A1
      (Apo-A1) in individual urine from patients with bladder cancer, which was
      confirmed by Western blot results. A further analysis of the urinary Apo-A1
      levels by an enzyme-linked immunosorbent assay yielded results that were
      consistent with the Western blot, and suggested Apo-A1 could provide diagnostic
      utility to distinguish patients with bladder cancer from healthy controls at
      19.21 ng/ml. Further validation assay in a larger number of urine samples (n=379)
      showed that Apo-A1 could be used as a biomarker to diagnosis bladder cancer with
      a sensitivity and specificity of 89.2% and 84.6% respectively. Moreover, the
      application of exfoliative urinary cytology in combination with the urine Apo-A1
      detection could significantly increased the sensitivity in detecting bladder
      cancer. Our data showed a significant relationship of expressed Apo-A1 was
      established between bladder cancer and normal controls. Apo-A1 could be a
      potential biomarker for the diagnosis of bladder cancer.

PMID- 24661884
TI  - Bovine Viral Diarrhoea Virus (BVDV) in Dairy Cattle: A Matched Case-Control
      Study.
AB  - Bovine viral diarrhoea virus (BVDV) causes one of the most important diseases of
      cattle in terms of economic costs and welfare. The aims were to estimate herd
      prevalence and to investigate the factors associated with antibodies in bulk tank
      milk (BTM) in dairy herds through a matched case-control study. To estimate herd
      prevalence, BTM samples were randomly selected (n = 314) from a population (N =
      1604). The true prevalence of BVDV was 24.3% (CI 95% = 20.1-29.3%). For the case
      control study, BVDV antibody-positive herds (high antibody titres) were
      classified as cases (n = 21) and matched (n = 63) by milk production with herds
      presenting low antibody titres (ratio of 1 : 3). Three multivariable models were
      built: 1) full model, holding all 21 variables, and two models divided according
      to empirical knowledge and similarity among variables; 2) animal factor model;
      and 3) biosecurity model. The full model (model 1) identified: age as a culling
      criteria (OR = 0.10; CI 95% = 0.02-0.39; P < 0.01); farms that provided milk to
      other industries previously (OR = 4.13; CI 95% = 1.17-14.49; P = 0.02); and
      isolation paddocks for ill animals (OR = 0.14; CI 95% = 0.01-0.26; P = 0.02). The
      biosecurity model revealed a significant association with the use of natural
      mating (OR = 9.03; CI 95% = 2.14-38.03; P < 0.01); isolation paddocks for ill
      animals (OR = 0.06; CI 95% = 0.05-0.83; P = 0.03); years providing milk for the
      same industry (OR = 0.94; CI 95% = 0.91-0.97; P = 0.02); and direct contact over
      fences among cattle of neighbouring farms (OR = 5.78; CI 95% = 1.41-23.67; P =
      0.04). We recommend the application of grouping predictors as a good choice for
      model building because it could lead to a better understanding of disease
      exposure associations.

PMID- 24661885
TI  - [Platypnea-orthodeoxia syndrome: a rare cause of severe hypoxemia].
AB  - INTRODUCTION: The platypnea-orthodeoxia syndrome (PO) includes: (i) a dyspnea
      increasing with orthostatism and decreasing in supine position, (ii) wide
      positional range in arterial oxygen saturation with tachycardia, (iii) and
      hypoxemia refractory to oxygen therapy. This syndrome is usually related to a
      cardiac right-left shunt, and rarely to a pulmonary shunt. OBSERVATION: We report
      a case of a patient presenting with a post-lung infection dyspnea associated with
      severe hypoxemia and shunt effect at blood gas. Contrast-enhanced CT-scan showed
      no pulmonary embolism. PO syndrome was suspected given the transcutaneous blood
      oxygen saturation variation from 90% in supine position to 60% in standing
      position, tachycardia, and absence of response to the intensive oxygen therapy.
      CONCLUSION: This syndrome should be known by physicians as a possible
      differential diagnose for refractory dyspnea to oxygen since effective treatment
      is available.

PMID- 24661886
TI  - Recovery, chemical and rheological characterization of gum from Assyrian pulm.
AB  - The extraction of gum from Assyrian pulm fruit (APH) was performed by microwave
      assisted extraction technique. A Box-Behnken design (BBD) was applied to evaluate
      the effects of three independent variables (power of microwave (X1: 50-350W),
      extraction time (X2: 20-90min), and extraction temperature (X3: 50-90 degrees C))
      on the extraction yield of APH. The effect of temperature and concentration on
      flow behavior of gum solution was studied. The viscosity of 2% APH solution was
      0.55Pas at a shear rate of 10s(-1) at 20 degrees C. The viscosity of fully
      hydrated gum solutions decreased as temperature increase. It was found that
      increasing the temperature from 10 to 60 degrees C causing the viscosity to
      decrease about 87% at shear rate 0.1s(-1) and 98% at shear rate 500s(-1). The
      correlation analysis of the mathematical-regression model indicated that
      quadratic polynomial model could be employed to optimize the microwave extraction
      of APH. The optimal conditions to obtain the highest extraction of APH (18.19+/
      0.26%) were as follows: microwave power, 330W; extraction time, 80.67min and
      extraction temperature, 82 degrees C. 

PMID- 24661887
TI  - Retrograded maize starch used as a medium to enrich Monascus from the air in
      winter.
AB  - Red pigments extracted from fungus Monascus are used for food coloration in
      China. Wild-growing Monascus spores are usually enriched in the yeast and mold
      media in the air, but those media are also favorable for yeast and bacteria. In
      the paper, Monascus species have grown in retrograded maize starch lain in air
      outdoors in winter, molds, yeast or bacteria colonies have been absent. Then a
      medium of the retrograded maize starch for enriching Monascus in the air is
      explored and its physicochemical properties are determined by ordinary camera
      photos, NMR, SEM spectra and X-ray diffraction. The lamellar structure of frozen
      retrograded maize starch, whose interlamellar spacing is about 2MUm, provides a
      favorable condition for Monascus spore to germinate and grow. 

PMID- 24661888
TI  - Water soluble sulfated-fucans with immune-enhancing properties from Ecklonia
      cava.
AB  - Water-soluble sulfated fucans isolated from Ecklonia cava were fractionated using
      an anion-exchange chromatography to investigate their molecular characteristics
      and immunomodulating activities. The crude fucoidan extract and purified
      fractions (EF1, EF2, and EF3) consisted mostly of different ratios of neutral
      sugars, proteins, sulfates, uronic acids, and their monosaccharide compositions
      were also significantly different. The backbone of the most immunoenhancing
      fraction, EF2, was mainly linked by (1->3)-linked fucopyranosyl and (1->4)-linked
      mannopyranosyl residues with sulfates at C-4 of fucopyranosyl units. The
      molecular weights of the crude fucoidan extract and purified fractions ranged
      from 8.3*10(3) to 442.6*10(3)g/mol. The crude extract, EF1 and EF2 stimulated
      RAW264.7 cells to produce considerable amounts of nitric oxide and cytokines. The
      treatment of cells with the sulfated fucans induced the degradation of Ikappa-B
      and the phosphorylation of MAPK in RAW264.7 cells, implying that they might
      stimulate RAW264.7 cells through the activation of NF-kappaB and MAPK pathways. 

PMID- 24661889
TI  - Performance behavior of modified cellulosic fabrics using polyurethane acrylate
      copolymer.
AB  - The surface of the cellulosic fabrics was modified using self-prepared emulsions
      of polyurethane acrylate copolymers (PUACs). PUACs were prepared by varying the
      molecular weight of polycaprolactone diol (PCL). The PCL was reacted with
      isophorone diisocyanate (IPDI) and chain was extended with 2-hydroxy ethyl
      acrylate (HEA) to form vinyl terminated polyurethane (VTPU) preploymer. The VTPU
      was further co-polymerized through free radical polymerization with butyl
      acrylate in different proportions. The FT-IR spectra of monomers, prepolymers and
      copolymers assured the formation of proposed PUACs structure. The various
      concentrations of prepared PUACs were applied onto the different fabric samples
      using dip-padding techniques. The results revealed that the application of
      polyurethane butyl acrylate copolymer showed a pronounced effect on the tear
      strength and pilling resistance of the treated fabrics. 

PMID- 24661890
TI  - Preparation, physical-chemical and biological characterization of chitosan
      nanoparticles loaded with lysozyme.
AB  - A commercially available chitosan (CS) was employed in the formulation of
      nanoparticles loaded with lysozyme (LZ) as antimicrobial protein drug model. Due
      to the variability of commercially available batches of chitosans and to the
      strict dependence of their physical and biological properties to the molecular
      weight (Mw) and deacetylation degree (DD) of the material, the CS was fully
      characterized resulting in weight-average molecular weight of 108,120g/mol and DD
      of 92%. LZ-loaded nanoparticles (LZ-NPs) of 150nm diameter were prepared by
      inotropic gelation. The nanoparticles were effectively preserving the
      antibacterial activity of the loaded enzyme, which was slowly released over 3
      weeks in vitro and remained active toward Staphylococcus epidermidis up to 5 days
      of incubation. Beyond the intrinsic antibacterial activity of CS and LZ, the LZ
      NPs evidenced a sustained antibacterial activity that resulted in about 2 log
      reduction of the number of viable S. epidermidis compared to plain CS
      nanoparticles. Furthermore, the LZ-NPs showed a full in vitro cytocompatibility
      toward murine fibroblasts and, in addition to the potential antimicrobial
      applications of the developed system, the proposed study could serve as an
      optimal model for development of CS nanoparticles carrying antimicrobial peptides
      for biomedical applications. 

PMID- 24661891
TI  - A pilot-scale homogenization-assisted negative pressure cavitation extraction of
      Astragalus polysaccharides.
AB  - This paper reported a new, green and effective extraction technique for
      polysaccharides, namely homogenization-assisted negative pressure cavitation
      extraction (HNPCE), which succeeded in the extraction of Astragalus
      polysaccharides (APs). Central composite design and kinetic model were applied to
      optimize the extraction conditions, and the optimal parameters were obtained as
      follows: homogenization time 70s, negative pressure -0.068MPa, extraction
      temperature 64.8 degrees C, ratio of water to material 13.4 and extraction time
      53min. The proposed method exhibited considerable predominance in terms of higher
      APs yield (16.74%) with much lower temperature and shorter duration, as against
      the reported hot water extraction method (14.33% of APs yield with 100 degrees C
      and 3h). Moreover, FT-IR results showed that HNPCE method did not alter the
      primary structure of polysaccharides. Furthermore, the pilot-scale application of
      HNPCE was successfully performed with 16.62% of APs yield. Thus, HNPCE is an
      excellent alternative method for the extraction of polysaccharides from
      Astragalus or other plant materials in industry. 

PMID- 24661892
TI  - Clinical and anatomic outcomes after carotid endarterectomy.
AB  - OBJECTIVE: The purpose of this study was to examine 30-day and long-term outcomes
      after carotid endarterectomy (CEA) in a contemporary series and to identify
      variables associated with stroke and death after CEA. METHODS: This was a
      retrospective review of patients undergoing an isolated CEA at a single
      institution between January 1989 and December 2005. Primary study end points were
      30-day and long-term overall stroke, ipsilateral stroke, and death. Secondary end
      points were recurrent stenosis (>70% stenosis) and reintervention. Kaplan-Meier
      analysis was used to create survival curves for the long-term study end points.
      Multivariate models were created to identify variables associated with the study
      end points. RESULTS: During the study period, 3014 CEAs were performed on 2644
      patients (mean age, 71.0 +/- 8.9 years; 60.9% male; 33.5% symptomatic; 37%
      primary closure), with mean follow-up of 7.0 years. The 30-day ipsilateral
      stroke, death, and combined ipsilateral stroke/death rates were 1.3%, 1.1%, and
      2.2%, respectively. Previous ipsilateral CEA or neck dissection for cancer
      (hazard ratio [HR], 3.68; P = .0081) and symptomatic disease (HR, 2.45; P =
      .0071) were predictive of 30-day ipsilateral stroke. Stroke-free survival was
      93.8% at 4 years and 86.9% at 10 years. Diabetes (HR, 1.94; P < .0001),
      symptomatic disease (HR, 1.75; P < .0001), female gender (HR, 1.34; P = .035),
      and increasing age (HR, 1.02; P < .0001) were predictors of long-term overall
      stroke. Ipsilateral stroke-free survival was 97.6% at 5 years and 94.6% at 10
      years, respectively. Contralateral occlusion (HR, 2.06; P = .025) and symptomatic
      disease (HR, 1.87; P = .003) were predictors of ipsilateral stroke, whereas
      antilipid therapy was protective (HR, 0.65; P = .049). Overall survival was 70.1%
      at 5 years and 42.2% at 10 years, with no difference between symptomatic and
      asymptomatic patients. Although a variety of comorbidities were associated with
      inferior late survival, as anticipated, female gender (HR, 0.89; P = .016) and
      lipid-lowering therapy (HR, 0.69; P < .0001) were protective. Reintervention was
      3.4% at 5 years and 6.6% at 10 years, with primary closure (vs patch
      angioplasty/eversion) increasing the risk of reintervention (HR, 1.72; P = .007).
      CONCLUSIONS: CEA has favorable perioperative and long-term clinical and anatomic
      outcomes with respect to its goal of stroke prevention for symptomatic and
      asymptomatic patients. Adjuvant medical therapy (antilipid) has increased overall
      and ipsilateral stroke-free survival.

PMID- 24661893
TI  - Double giant pseudoaneurysms of the aortic root and arch after ascending aorta
      replacement.

PMID- 24661894
TI  - Percutaneous endovascular repair of adult aortic coarctation.

PMID- 24661895
TI  - High-output heart failure due to post-traumatic peroneal arteriovenous fistula.

PMID- 24661896
TI  - Bayesian network meta-analysis of nitinol stents, covered stents, drug-eluting
      stents, and drug-coated balloons in the femoropopliteal artery.
AB  - OBJECTIVE: Several randomized controlled trials (RCTs) have shown the superiority
      of some of these technologies over balloon angioplasty, but direct comparisons
      between these treatment options are lacking. The authors conducted a network meta
      analysis of RCTs comparing bare nitinol stents, covered nitinol stents,
      paclitaxel- or sirolimus-eluting stents (PES or SES), and paclitaxel-coated
      balloons (PCB) with plain balloon angioplasty or with each other in the
      femoropopliteal artery (PROSPERO registry: CRD42013004845). METHODS: Sixteen RCTs
      comprising 2532 patients with 4227 person-years of follow-up were analyzed on an
      intention-to-treat basis. Bayesian random effects Poisson and binomial models
      were used for mixed treatment comparisons (WinBUGS). Clinical heterogeneity was
      accounted for by incorporating a meta-regression model on trial-specific baseline
      risk. End points included technical success, vascular restenosis, target lesion
      revascularization, and major amputations. Pairwise odds ratios and rate ratios
      (ORs and RRs) of absolute treatment effects were calculated, and the
      probabilities of each treatment being best are reported. Summary estimates are
      reported as the posterior median and associated credible intervals (CrIs) that
      serve the same purpose as confidence intervals in the context of the Bayesian
      framework. Extensive sensitivity, meta-regression, and network consistency
      analyses were performed to evaluate heterogeneity. RESULTS: Technical success was
      highest with covered stents (pooled OR, 13.6; 95% CrI, 3.3-31.1, probability best
      82%) followed by uncovered stents (pooled OR, 7.0; 95% CrI, 2.6-129, probability
      best 18%) when compared with balloon angioplasty (reference treatment). Vascular
      restenosis was lowest with PES (RR, 0.43; 95% CrI, 0.16-1.18, probability best
      45%) followed by PCB (RR, 0.43; 95% CrI, 0.26-0.67, probability best 42%). Target
      lesion revascularization was lowest with PCB (RR, 0.36; 95% CrI, 0.23-0.55,
      probability best 56%) followed by PES (RR, 0.42; 95% CrI, 0.16-1.06, probability
      best 33%). Major amputations were rare in all treatment and control groups
      (pooled amputation rate of 0.7 events per 100 person-years). CONCLUSIONS:
      Immediate technical success is better with the use of covered stents, whereas
      paclitaxel-eluting stents and paclitaxel-coated balloons offer the best long-term
      results in the femoropopliteal artery.

PMID- 24661897
TI  - Predictors of aortic growth in uncomplicated type B aortic dissection.
AB  - BACKGROUND: Patients with uncomplicated acute type B aortic dissection (ABAD)
      generally can be treated with conservative medical management. However, these
      patients may develop aortic enlargement during follow-up, with the risk for
      rupture, which necessitates intervention. Several predictors have been studied in
      recent years to identify ABAD patients at high risk for aortic enlargement who
      may benefit from early surgical or endovascular intervention. This study
      systematically reviewed and summarized the current available literature on
      prognostic variables related to aortic enlargement during follow-up in
      uncomplicated ABAD patients. METHODS: Studies were included if they reported
      predictors of aortic growth in uncomplicated ABAD patients. Studies about type A
      aortic dissection, aortic aneurysm, intramural hematoma, or ABAD that required
      acute intervention were excluded. RESULTS: A total of 18 full-text articles were
      selected. The following predictors of aortic growth in ABAD patients were
      identified: age <60 years, white race, Marfan syndrome, high fibrinogen-fibrin
      degradation product level (>=20 MUg/mL) at admission, aortic diameter >=40 mm on
      initial imaging, proximal descending thoracic aorta false lumen (FL) diameter
      >=22 mm, elliptic formation of the true lumen, patent FL, partially thrombosed
      FL, saccular formation of the FL, presence of one entry tear, large entry tear
      (>=10 mm) located in the proximal part of the dissection, FL located at the inner
      aortic curvature, fusiform dilated proximal descending aorta, and areas with
      ulcer-like projections. Tight heart rate control (<60 beats/min), use of calcium
      channel blockers, thrombosed FL, two or more entry tears, FL located at the outer
      aortic curvature, and circular configuration of the true lumen were associated
      with negative or limited aortic growth. CONCLUSIONS: Several predictors might be
      used to identify those ABAD patients at high risk for aortic growth. Although
      conservative management remains indicated in uncomplicated ABAD, these patients
      might benefit from closer follow-up or early endovascular intervention.

PMID- 24661898
TI  - Defining, aligning, or declining do not resuscitate during surgery.
AB  - A Professor A. Droit, 93 years of age, formerly your college ethics teacher,
      developed a painful ischemic foot from distal aortic blockage. A daughter, who is
      a nurse, brought him to the hospital. He has multiple comorbidities, including
      leukemia for which he is getting chemotherapy. He agrees to surgery but hands you
      a completed do not resuscitate (DNR) form and insists it be honored throughout
      his care. As the operative wound is being closed, he has a slow ventricular
      tachycardia, which does not respond to intravenous therapy. You should: 

PMID- 24661899
TI  - 3D laser measurements of bare and shod feet during walking.
AB  - This article presents a new system for 3D foot-shape measurements during walking.
      It is based on the laser-triangulation, multiple-line-illumination and color
      modulation techniques. It consists of a walking stage and four measuring modules
      that simultaneously acquire the foot shape from the top, bottom and side views.
      The measuring speed is 30 fps. Custom-developed software makes it possible to
      analyze the foot's dimensions at an arbitrary cross-section by means of the
      width, height, girth and section orientation. Six subjects were measured during
      bare and shod walking, and the bare foot and the outside dimensions of the
      footwear during the entire stance phase are presented. The relative measurement
      repeatability of a single subject is 0.5% for bare foot and 1% for shod foot.
      This means that it is possible to study the differences between various
      influences on the foot-shape dynamics, such as a bare/shod foot, different
      loading conditions and the shoe's stiffness condition.

PMID- 24661900
TI  - Infant robot-assisted laparoscopic upper urinary tract reconstructive surgery.
AB  - OBJECTIVE: Our aim was to assess the outcomes of infant robot-assisted
      laparoscopic (RAL) upper urinary tract reconstruction. MATERIALS AND METHODS: The
      medical records of all infants who underwent RAL upper urinary tract
      reconstruction were reviewed. Patients less than 1 year of age at surgery were
      included. Patient demographics, intraoperative details, narcotic usage, and
      complications were reviewed. RESULTS: Ten infants met the study criteria. There
      were five right and five left-sided procedures. Eight pyeloplasties (4 right, 4
      left) and two ureteroureterostomies (1 right single system, 1 left duplex system)
      were performed. The median age was 8 months (range 3-12 months). Median weight
      was 7.7 kg (range 5.8-10.9 kg). Median operative time was 128 min (range 95-205
      min). There was no significant blood loss or intraoperative complications. One
      (10%) patient received a regional block. Eight (80%) patients did not receive
      postoperative narcotics. Median hospital stay was 1 day (range 1-2). Median
      follow-up was 10 months (range 3-18 months). Complications included one urinary
      leak, one ileus, and one urinary tract infection. Hydronephrosis improved in all
      patients. CONCLUSIONS: Infant RAL upper urinary tract reconstruction is
      technically feasible, safe, and effective. It can be applied for duplication
      anomalies and single system obstructions in infants.

PMID- 24661901
TI  - Decreased delay discounting in former cigarette smokers at one year after
      treatment.
AB  - Current cigarette smokers exhibit greater delay discounting relative to ex
      smokers. However, few studies have assessed longitudinal changes in delay
      discounting and cigarette smoking. The purpose of this study was to assess
      changes in delay discounting of hypothetical monetary rewards and smoking among
      treatment-seeking smokers (N=80) at baseline, after 6 weeks of behavioral
      treatment, and at 12-month follow-up. Results showed no changes in delay
      discounting in either smokers or abstainers at the end-of-treatment. In contrast,
      at 12-month follow-up, significant decreases in delay discounting were observed
      in abstainers while delay discounting remained the same for smokers. To our
      knowledge, this is the first study to observe significant decreases in delay
      discounting following prolonged smoking abstinence. Such findings provide
      evidence that delay discounting may have more state-like characteristics than
      previously believed.

PMID- 24661903
TI  - Management of chest pain: a prospective study from Norwegian out-of-hours primary
      care.
AB  - BACKGROUND: Chest pain is a common diagnostic challenge in primary care and
      diagnostic measures are often aimed at confirming or ruling out acute ischaemic
      heart disease. The aim of this study was to investigate management of patients
      with chest pain out-of-hours, including the use of ECG and laboratory tests,
      assessment of severity of illness, and the physicians' decisions on treatment and
      admittance to hospital. METHODS: Data were registered prospectively from four
      Norwegian casualty clinics. Data from structured telephone interviews with 100
      physicians shortly after a consultation with a patient presenting at the casualty
      clinic with "chest pain" were analysed. RESULTS: A total of 832 patients with
      chest pain were registered. The first 100 patients (corresponding doctor-patient
      pairs) were included in the study according to the predefined inclusion criteria.
      Median age of included patients was 46 years, men constituted 58%. An ECG was
      taken in 92 of the patients. Of the 24 patients categorised to acute level of
      response, 15 had a NACA-score indicating a potentially or definitely life
      threatening medical situation. 50 of the patients were admitted to a hospital for
      further management, of which 43 were thought to have ischaemic heart disease.
      Musculoskeletal pain was the second most common cause of pain (n = 22). Otherwise
      the patients were thought to have a variety of conditions, most of them managed
      at a primary care level. CONCLUSIONS: Patients with chest pain presenting at out
      of-hours services in Norway are investigated for acute heart disease, but less
      than half are admitted to hospital for probable acute coronary syndrome, and only
      a minority is given emergency treatment for acute coronary syndrome. A wide
      variety of other diagnoses are suggested by the doctors for patients presenting
      with chest pain. Deciding the appropriate level of response for such patients is
      a difficult task, and both over- and under-triage probably occur in out-of-hours
      primary care.

PMID- 24661904
TI  - Management practices as risk factors for the presence of bulk milk antibodies to
      Salmonella, Neospora caninum and Leptospira interrogans serovar hardjo in Irish
      dairy herds.
AB  - A survey of management practices in 309 Irish dairy herds was used to identify
      risk factors for the presence of antibodies to Salmonella, Neospora caninum and
      Leptospira interrogans serovar hardjo in extensively managed unvaccinated dairy
      herds. A previous study documented a herd-level seroprevalence in bulk milk of
      49%, 19% and 86% for Salmonella, Neospora caninum and leptospira interrogans
      serovar hardjo, respectively in the unvaccinated proportion of these 309 herds in
      2009. Association analyses in the present study were carried out using multiple
      logistic regression models. Herds where cattle were purchased or introduced had a
      greater likelihood of being positive to leptospira interrogans serovar hardjo
      (P<0.01) and Salmonella (P<0.01). Larger herds had a greater likelihood of
      recording a positive bulk milk antibody result to leptospira interrogans serovar
      hardjo (P<0.05). Herds that practiced year round calving were more likely to be
      positive to Neospora caninum (P<0.05) compared to herds with a spring-calving
      season, with no difference in risk between herds that practiced split calving
      compared to herds that practiced spring calving. No association was found between
      presence of dogs on farms and prevalence of Neospora caninum possibly due to
      limited access of dogs to infected materials including afterbirths. The
      information from this study will assist in the design of suitable control
      programmes for the diseases under investigation in pasture-based livestock
      systems. 

PMID- 24661902
TI  - p70S6 kinase mediates breast cancer cell survival in response to surgical wound
      fluid stimulation.
AB  - In early breast cancer, local relapses represent a determinant and not simply an
      indicator of risk for distant relapse and death. Notably, 90% of local
      recurrences occur at or close to the same quadrant of the primary cancer.
      Relevance of PI3K/mTOR/p70S6K signaling in breast tumorigenesis is very well
      documented. However, the pathway/s involved in the process of breast cancer local
      relapse are not well understood. The ribosomal protein p70S6K has been implicated
      in breast cancer cell response to post-surgical inflammation, supporting the
      hypothesis that it may be crucial also for breast cancer recurrence. Here, we
      show that p70S6K activity is required for the survival of breast cancer cells
      challenged in "hostile" microenvironments. We found that impairment of p70S6K
      activity in breast cancer cells strongly decreased their tumor take rate in nude
      mice. In line with this observation, if cells were challenged to grow in
      anchorage independence or in clonogenic assay, growth of colonies was strongly
      dependent on an intact p70S6K signaling. This in vitro finding was particularly
      evident when breast cancer cells were grown in the presence of wound fluids
      harvested following surgery from breast cancer patients, suggesting that the
      stimuli present in the post-surgical setting at least partially relied on
      activity of p70S6K to stimulate breast cancer relapse. From a mechanistic point
      of view, our results indicated that p70S6K signaling was able to activate Gli1
      and up-regulate the anti-apoptotic protein Bcl2, thereby activating a survival
      response in breast cancer cells challenged in hostile settings. Our work
      highlights a previously poorly recognized function of p70S6K in preserving breast
      cancer cell survival, which could eventually be responsible for local relapse and
      opens the way to the design of new and more specific therapies aiming to restrain
      the deleterious effects of wound response.

PMID- 24661905
TI  - Partial versus maximal forced exhalations in COPD: enhanced signal detection for
      novel therapies.
AB  - BACKGROUND: Evaluation of novel compounds for COPD often relies on FEV1 for
      signal detection. Partial forced exhalations from end-tidal inspiration (PEFV)
      might complement FEV1 in identifying such a signal. We examined the prevalence of
      bronchodilator response (BDR) using PEFV and FEV1 in patients with COPD. METHODS:
      110 consecutive COPD patients were tested prospectively with PEFV and maximal
      expiratory flow before and after inhalation of a short-acting beta2 agonist
      (salbutamol, 400 MUg). Partial flow at 800 ml above residual volume was derived
      from the PEFV (PF800). Significant changes in PF800 and/or FEV1 were set at the
      upper 95% confidence interval after placebo (n = 28). RESULTS: Four groups were
      identified by the presence (+) or absence (-) of a BDR: Group 1 [PF800 (-)FEV1(
      )] when no change was observed (n = 31), Group 2 [PF800(+)FEV1(-)] when PF800
      alone improved (n = 31), Group 3 [PF800(-)FEV1(+)] when FEV1 alone improved (n =
      26), and Group 4 [PF800(+)FEV1(+)] when both variables improved (n = 18). There
      were 35 non-responders in any parameter, and 75/110 subjects who showed a
      response in at least one parameter. The changes in PF800 and FEV1 were not
      correlated suggesting these assess different airway generations. CONCLUSIONS: The
      use of PF800 increased detection of a BDR in COPD compared to FEV1 alone and may
      reflect small airway responses. The PEFV maneuver is simple, repeatable and may
      avoid some of the theoretical disadvantages of FEV1. The role of PF800 for
      evaluating novel anti-inflammatory agents remains to be determined.

PMID- 24661906
TI  - Intensification and sedentism in the terminal Pleistocene Natufian sequence of el
      Wad Terrace (Israel).
AB  - Measuring subsistence intensification in the archaeofaunal record has provided
      strong evidence for socioeconomic shifts related to sedentarization in the
      terminal Pleistocene Mediterranean Basin, but the precise timing and scale of the
      intensification trend and its place in the evolution of settled societies remain
      contentious. New archaeofaunal data from the key Natufian sequence of el-Wad
      Terrace (Mount Carmel, Israel, ca. 15.0-11.7 ka [thousands of years ago]) is used
      here to clarify and contextualize paleoeconomy and mobility trends in the latest
      Pleistocene Levant, representing the culmination of Epipaleolithic subsistence
      strategies. Taphonomic variables serve as supplementary indicators of habitation
      function and occupation intensity along the sequence. At el-Wad, a very broad
      range of animals, mostly small to medium in size, were captured and consumed.
      Consumption leftovers were discarded in intensively occupied domestic spaces and
      suffered moderate attrition. The Early (ca. 15.0-13.7/13.0 ka) and Late (ca.
      13.7/13.0-11.7 ka) Natufian phases display some differences in prey exploitation
      and taphonomic markers of occupation intensity, corresponding with other
      archaeological signals. We further set the intra-Natufian taxonomic and
      demographic trends in perspective by considering the earlier Epipaleolithic
      sequence of the same region, the Israeli coastal plain. Consequently, we show
      that the Early Natufian record constituted an important dietary shift related to
      greater occupation intensity and sedentarization, rather than a gradual
      development, and that the Late Natufian record appears to be maintaining, if not
      amplifying, many of these novel signals. These conclusions are important for
      understanding the mode and tempo of the transition to settled life in human
      evolution. 

PMID- 24661907
TI  - Sox9 and Hif-2alpha regulate TUBB3 gene expression and affect ovarian cancer
      aggressiveness.
AB  - SOX9 [(sex determining region Y)-box9] gene has been implicated in the
      development and progression of different neoplasms. This study investigated the
      role of Sox9 in the expression of TUBB3 gene, a marker of aggressiveness in
      ovarian cancer (OC), encoding betaIII-tubulin protein. Gene expression was
      assessed by quantitative polymerase chain reaction (qPCR) in OC models. Using
      chromatin immunoprecipitation (ChIP) we found that Sox9 engages TUBB3 promoter at
      minus 980 base pairs from the transcriptional start site with transcriptional
      enhancing effects. Furthermore we found that Sox9 is a downstream target of Hif
      2alpha, a transcription factor encoded by endothelial PAS domain protein-1
      (EPAS1). Hypoxic microenvironment is a common feature of solid tumors associated
      with cancer aggressiveness. In the present work we found that knockdown of either
      SOX9 or EPAS1 abolished TUBB3 gene induction in hypoxia. This phenomenon was
      associated with a decrease in the number of cell colonies capable of growing in
      an anchorage-independent way. Using a nanofluidic genetic analyzer, the
      expression of SOX9, TUBB3 and EPAS1 was evaluated in 182 OC specimens. Double
      staining immunohistochemistry was employed to evaluate the expression and
      prognostic role of both Sox9 and betaIII-tubulin. Results obtained in cellular
      models matched the pattern of clinical specimens. We documented a direct
      correlation among the expression of EPAS1, SOX9 and TUBB3 at mRNA level. Patients
      displaying no expression for the three genes had the best outcome. A poor
      prognosis significant in multivariate analysis was visible in patients featuring
      high expression of betaIII-tubulin and nuclear Sox9. CONCLUSIONS: Sox9 allows the
      survival of OC cells upon hypoxic condition, through the activation of betaIII
      tubulin expression and its aberrant activation in OC is prominent in patients
      with aggressive OC.

PMID- 24661908
TI  - Alterations in plasma lecithin:cholesterol acyltransferase and myeloperoxidase in
      acute myocardial infarction: implications for cardiac outcome.
AB  - BACKGROUND: The cholesterol esterifying enzyme, lecithin:cholesterol
      acyltransferase (LCAT), plays a key role in HDL maturation and remodeling.
      Myeloperoxidase (MPO) may compromise LCAT enzymatic activity. We tested the
      extent to which plasma LCAT activity is altered in acute myocardial infarction
      (MI) in conjunction with abnormal MPO levels. We also assessed the impact of LCAT
      and MPO on newly developed major adverse cardiovascular events (MACE). METHODS:
      Two-hundred one consecutive patients referred for acute chest pain of whom 134
      had MI (95 with ST-elevation) participated. Forty-five new MACE were ascertained
      during 1203 (range 13-1745) days of follow-up among 185 patients. Plasma LCAT
      activity was measured using an exogenous substrate assay. MPO mass was assayed by
      chemiluminescent microparticle immunoassay. RESULTS: Plasma LCAT activity was
      decreased by 15%, coinciding with 7-fold increased MPO levels in acute MI
      patients vs. patients with non-cardiac chest pain (p < 0.001 for both;
      correlation: r = -0.343, p < 0.001). MI at admission was associated independently
      with both lower plasma LCAT activity and higher MPO (age- and sex-adjusted odds
      ratio per 1 SD increment: 0.46 (95% CI, 0.31-0.68), p < 0.001 and 7.58 (95% CI,
      3.34-17.11), p < 0.001, respectively). In an analysis with LCAT and MPO together
      these associations were modestly attenuated. MPO mass (hazard ratio: 1.59 (95%
      CI, 1.15-2.19), p = 0.004), but not LCAT activity (hazard ratio: 0.87 (95% CI,
      0.65-1.19), p = 0.39), predicted newly manifest MACE. CONCLUSION: In acute MI
      patients, plasma LCAT activity is decreased coinciding with increased MPO levels.
      Higher MPO but not lower LCAT activity prospectively predicts adverse cardiac
      outcome.

PMID- 24661909
TI  - Expression of Tiam1 predicts lymph node metastasis and poor survival of lung
      adenocarcinoma patients.
AB  - BACKGROUND: To assess the value of Tiam1 in predicting lymph node metastasis and
      survival after curative resection in patients with lung adenocarcinoma. METHODS:
      Immunohistochemical staining for Tiam1 was performed on 98 adenocarcinoma and 30
      normal lung tissues. The association of Tiam1 protein expression with the
      clinicopathological characteristics and the prognosis of lung adenocarcinoma were
      subsequently assessed. RESULTS: Immunohistochemical analysis showed that 60 of 98
      (61.22%) adenocarcinoma tissues showed high expression of Tiam1, and high Tiam1
      expression was significantly associated with advanced TNM stage (P < 0.0005) and
      lymph node status (P < 0.0005) of lung adenocarcinoma. Moreover, the lung
      adenocarcinoma patients with low Tiam1 expression had higher overall survival
      than patients with high Tiam1 expression (log rank value = 10.805, P = 0.001).
      High expression of Tiam1 predicted poor overall survival of patients in stages I
      + II (P = 0.006). Furthermore, multivariate analysis indicated that high
      expression of Tiam1 protein was an independent prognostic factor for overall
      survival (P = 0.011) in patients with lung adenocarcinoma. CONCLUSION: These
      findings suggest for the first time that Tiam1 expression may be beneficial in
      predicting lymph node metastasis and survival of patients with lung
      adenocarcinoma. A future study will investigate whether Tiam1 can serve as a
      novel therapeutic target in lung adenocarcinoma. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1377798917111123.

PMID- 24661911
TI  - Abnormal functional connectivity density in children with anisometropic amblyopia
      at resting-state.
AB  - Amblyopia is a developmental disorder resulting from anomalous binocular visual
      input in early life. Task-based neuroimaging studies have widely investigated
      cortical functional impairments in amblyopia, but changes in spontaneous neuronal
      functional activities in amblyopia remain largely unknown. In the present study,
      functional connectivity density (FCD) mapping, an ultrafast data-driven method
      based on fMRI, was applied for the first time to investigate changes in cortical
      functional connectivities in amblyopia during the resting-state. We quantified
      and compared both short- and long-range FCD in both the brains of children with
      anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to
      the NSC, the AAC showed significantly decreased short-range FCD in the inferior
      temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices,
      as well as decreased long-range FCD in the premotor cortex, dorsal inferior
      parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore,
      most regions with reduced long-range FCD in the AAC showed decreased functional
      connectivity with occipital and posterior parietal cortices in the AAC. The
      results suggest that chronically poor visual input in amblyopia not only impairs
      the brain's short-range functional connections in visual pathways and in the
      frontal cortex, which is important for cognitive control, but also affects long
      range functional connections among the visual areas, posterior parietal and
      frontal cortices that subserve visuomotor and visual-guided actions, visuospatial
      attention modulation and the integration of salient information. This study
      provides evidence for abnormal spontaneous brain activities in amblyopia.

PMID- 24661910
TI  - Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a
      novel therapeutic target in medulloblastoma.
AB  - BACKGROUND: Medulloblastoma is the most common type of malignant brain tumor that
      afflicts children. Although recent advances in chemotherapy and radiation have
      improved outcomes, high-risk patients do poorly with significant morbidity.
      METHODS: To identify new molecular targets, we performed an integrated genomic
      analysis using structural and functional methods. Gene expression profiling in 16
      medulloblastoma patient samples and subsequent gene set enrichment analysis
      indicated that cell cycle-related kinases were associated with disease
      development. In addition a kinome-wide small interfering RNA (siRNA) screen was
      performed to identify kinases that, when inhibited, could prevent cell
      proliferation. The two genome-scale analyses were combined to identify key
      vulnerabilities in medulloblastoma. The inhibition of one of the identified
      targets was further investigated using RNAi and a small molecule inhibitor.
      RESULTS: Combining the two analyses revealed that mitosis-related kinases were
      critical determinants of medulloblastoma cell proliferation. RNA interference
      (RNAi)-mediated knockdown of WEE1 kinase and other mitotic kinases was sufficient
      to reduce medulloblastoma cell proliferation. These data prompted us to examine
      the effects of inhibiting WEE1 by RNAi and by a small molecule inhibitor of WEE1,
      MK-1775, in medulloblastoma cell lines. MK-1775 inhibited the growth of
      medulloblastoma cell lines, induced apoptosis and increased DNA damage at
      nanomolar concentrations. Further, MK-1775 was synergistic with cisplatin in
      reducing medulloblastoma cell proliferation and resulted in an associated
      increase in cell death. In vivo MK-1775 suppressed medulloblastoma tumor growth
      as a single agent. CONCLUSIONS: Taken together, these findings highlight mitotic
      kinases and, in particular, WEE1 as a rational therapeutic target for
      medulloblastoma.

PMID- 24661912
TI  - Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling
      mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist
      treatment.
AB  - Entorhinal cortex lesioning (ECL) causes an extensive deafferentation of the
      hippocampus that is classically followed by a compensatory reinnervation, where
      apolipoprotein E, the main extracellular lipid-carrier in the CNS, has been shown
      to play a crucial role by shuttling cholesterol to reconstructing neurons
      terminals. Hence, we investigated whether the ATP-binding cassette (ABC)
      transporters -A1 and -G1, known to regulate cellular cholesterol efflux and
      lipidation of the apolipoprotein E-containing lipoprotein complex are actively
      involved in this context of brain's plastic response to neurodegeneration and
      deafferentation. We assessed ABCA1 and ABCG1 mRNA and protein levels throughout
      the degenerative phase and the reinnervation process and evaluated the associated
      cholinergic sprouting following ECL in the adult mouse brain. We subsequently
      tested the effect of the pharmacological activation of the nuclear receptor LXR,
      prior to versus after ECL, on hippocampal ABCA1 and G1 expression and on
      reinnervation. ECL induced a time-dependent up-regulation of ABCA1, but not G1,
      that coincided with a significant increase in acetylcholine esterase (AChE)
      activity in the ipsilateral hippocampus. Pre-ECL, but not post-ECL i.p. treatment
      with the LXR agonist TO901317 also led to a significant increase solely in
      hippocampal ABCA1 expression, paralleled by increases in both AchE and
      synaptophysin protein levels in the deafferented hippocampus. Thus, ABCA1 and -G1
      are differentially regulated in the lesioned brain and upon treatment with an LXR
      agonist. Further, TO901317-induced up-regulation of ABCA1 appears to be more
      beneficial in a prevention (pre-lesion) than rescue (post-lesion) treatment; both
      findings support a central role for ABC transporters in brain plasticity. 

PMID- 24661913
TI  - Effects of intracerebroventricular corticotropin releasing factor on sensory
      evoked responses in the rat visual thalamus.
AB  - Corticotropin releasing factor (CRF) coordinates the brain's responses to stress.
      Recent evidence suggests that CRF-mediated activation of the locus coeruleus
      norepinephrine (LC-NE) system contributes to alterations in sensory signal
      processing during stress. However, it remains unclear whether these actions are
      dependent upon the degree of CRF release. Using intracerebroventricular (ICV)
      infusions, we examine the dose-dependent actions of CRF on sensory-evoked
      discharges of neurons in the dorsal lateral geniculate nucleus of the thalamus
      (dLGN). The LGN is the primary relay for visual signals from retina to cortex,
      receiving noradrenergic modulation from the LC. In vivo extracellular recording
      in anesthetized rats was used to monitor single dLGN neuron responses to light
      flashes at three different stimulus intensities before and after administration
      of CRF (0.1, 0.3, 1.0, 3.0 or 10.0 MUg). CRF produced three main effects on dLGN
      stimulus evoked activity: (1) increased magnitude of sensory evoked discharges at
      moderate doses, (2) decreased response latency, and (3) dose-dependent increases
      in the number of cells responding to a previously sub-threshold (low intensity)
      stimulus. These modulatory actions were blocked or attenuated by intra-LC
      infusion of a CRF antagonist prior to ICV CRF administration. Moreover, intra-LC
      administration of CRF (10 ng) mimicked the facilitating effects of moderate doses
      of ICV CRF on dLGN neuron responsiveness to light stimuli. These findings suggest
      that stressor-induced changes in sensory signal processing cannot be defined in
      terms of a singular modulatory effect, but rather are multi-dimensional and
      dictated by variable degrees of activation of the CRF-LC-NE system.

PMID- 24661914
TI  - Isoflurane inhibits occludin expression via up-regulation of hypoxia-inducible
      factor 1alpha.
AB  - The blood-brain barrier (BBB) is a functional structure which regulates and
      restricts the transfer of circulating molecules and immune cells into the central
      nervous system. The barrier is formed by the presence of tight junctions (TJ)
      between the specialized brain endothelial cells. The volatile anesthetic
      isoflurane may affect the permeability of the BBB. Previous studies have proven
      that isoflurane alters hypoxia-inducible factor-1alpha (HIF-1alpha) expression,
      which may affect the TJ proteins; however, the mechanism of how TJ proteins are
      affected by isoflurane is still unclear. Primary human brain vascular endothelial
      cells (HBVEC) were exposed to isoflurane at various concentrations (0-2.5%) and
      different time periods (0-6 h). The cell viability, occludin expression,
      paracellular permeability, VEGF expression, TGF-beta3 expression and occludin
      protein endocytosis were quantified. Isoflurane treatment induced a time- and
      concentration-dependent decrease in occludin mRNA and protein levels in HBVEC.
      This effect was partially abrogated by silencing the HIF-1alpha expression.
      Isoflurane could activate HIF-1alpha, and the overexpression HIF-1alpha up
      regulated the level of VEGF and TGF-beta3, VEGF decreased the expression of
      occludin and TGF-beta3 accelerated the endocytosis of occludin. RNA interference
      targeting HIF-1alpha reduced both VEGF and TGF-beta3 expression after isoflurane
      treatment. CONCLUSION: This study provides direct evidence in vitro that exposing
      isoflurane to HBVECs can trigger HIF-1alpha activation, leading to lower protein
      levels of occludin, and increased permeability of the BBB.

PMID- 24661916
TI  - Biologic targeted therapies in pediatric rheumatology.

PMID- 24661915
TI  - Identification of sexually dimorphic genes in the neonatal mouse cortex and
      hippocampus.
AB  - The cerebral cortex and hippocampus are important for the control of cognitive
      functions and social behaviors, many of which are sexually dimorphic and tightly
      regulated by gonadal steroid hormones via activation of their respective nuclear
      receptors. As different levels of sex steroid hormones are present between the
      sexes during early development and their receptors act as transcription factors
      to regulate gene expression, we hypothesize that sexually dimorphic gene
      expression in the developing mouse cortex and hippocampus might result in sex
      differences in brain structures and neural circuits governing distinct behaviors
      between the sexes as adults. To test our hypothesis, we used gene expression
      microarrays to identify 90 candidate genes differentially expressed in the
      neonatal cortex/hippocampus between male and female mice, including 55 male
      biased and 35 female-biased genes. Among these genes, sexually dimorphic
      expression of eight sex chromosome genes was confirmed by reverse transcription
      with quantitative PCR (RT-qPCR), including three located on the X chromosome
      (Xist, Eif2s3x, and Kdm6a), three on the Y chromosome (Ddx3y, Eif2s3y, and
      Kdm5d), and two in the pseudoautosomal region of the X and Y chromosomes (Erdr1
      and Mid1). In addition, five autosomal genes (Cd151, Dab2, Klk8, Meg3, and Prkdc)
      were also validated for their sexually dimorphic expression in the neonatal mouse
      cortex/hippocampus. Gene Ontology annotation analysis suggests that many of these
      sexually dimorphic genes are involved in histone modifications, cell
      proliferation/death, androgen/estrogen signaling pathways, and synaptic
      organization, and these biological processes have been implicated in differential
      neural development, cognitive function, and neurological diseases between the
      sexes. 

PMID- 24661918
TI  - [Reply: Limitation of life support and organ donation in the intensive care
      unit].

PMID- 24661917
TI  - Blood culture differential time to positivity enables safe catheter retention in
      suspected catheter-related bloodstream infection: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the clinical usefulness and safety of the differential
      time-to-positivity (DTP) method for managing the suspicion of catheter-related
      bloodstream infection (CR-BSI) in comparison with a standard method that includes
      catheter removal in critically ill patients. METHODS-DESIGN: A prospective
      randomized study was carried out. SETTING: A 16-bed clinical-surgical ICU (July
      2007-February 2009). INTERVENTIONS: Patients were randomly assigned to one of two
      groups at the time CR-BSI was suspected. In the standard group, a standard
      strategy requiring catheter withdrawal was used to confirm or rule out CR-BSI. In
      the DTP group, DTP without catheter withdrawal was used to confirm or rule out CR
      BSI. MEASUREMENTS: clinical and microbiological data, CR-BSI rates, unnecessary
      catheter removals, and complications due to new puncture or to delays in catheter
      removal. RESULTS: Twenty-six patients were analyzed in each group. In the
      standard group, 6 of 37 suspected episodes of CR-BSI were confirmed and 5
      colonizations were diagnosed. In the DTP group, 5 of 26 suspected episodes of CR
      BSI were confirmed and four colonizations were diagnosed. In the standard group,
      all catheters (58/58, 100%) were removed at the time CR-BSA was suspected,
      whereas in the DTP group, only 13 catheters (13/41, 32%) were removed at
      diagnosis, and 10 due to persistent septic signs (10/41, 24%). In cases of
      confirmed CR-BSI, there were no differences between the two groups in the
      evolution of inflammatory parameters during the 48hours following the suspicion
      of CR-BSI. CONCLUSIONS: In critically ill patients with suspected CR-BSI, the DTP
      method makes it possible to keep the central venous catheter in place safely.

PMID- 24661919
TI  - Intensive care unit without walls: seeking patient safety by improving the
      efficiency of the system.
AB  - The term "ICU without walls" refers to innovative management in Intensive Care,
      based on two key elements: (1) collaboration of all medical and nursing staff
      involved in patient care during hospitalization and (2) technological support for
      severity early detection protocols by identifying patients at risk of
      deterioration throughout the hospital, based on the assessment of vital signs
      and/or laboratory test values, with the clear aim of improving critical patient
      safety in the hospitalization process. At present, it can be affirmed that there
      is important work to be done in the detection of severity and early intervention
      in patients at risk of organ dysfunction. Such work must be adapted to the
      circumstances of each center and should include training in the detection of
      severity, multidisciplinary work in the complete patient clinical process, and
      the use of technological systems allowing intervention on the basis of monitored
      laboratory and physiological parameters, with effective and efficient use of the
      information generated. Not only must information be generated, but also efficient
      management of such information must also be achieved. It is necessary to improve
      our activity through innovation in management procedures that facilitate the work
      of the intensivist, in collaboration with other specialists, throughout the
      hospital environment. Innovation is furthermore required in the efficient
      management of the information generated in hospitals, through intelligent and
      directed usage of the new available technology. 

PMID- 24661920
TI  - [Changes observed in three quality indicators after the implementation of
      improvement strategies in the respiratory intensive care unit].
AB  - OBJECTIVE: To compare the results of quality monitoring after the implementation
      of improvement strategies in the respiratory intensive care unit (RICU). DESIGN:
      A prospective, comparative, longitudinal and interventional study was carried
      out. SETTING: The RICU of Hospital General de Mexico (Mexico). PATIENTS: All
      patients admitted to the RICU from March 2012 to March 2013. INTERVENTIONS: An
      evidence-based bundle of interventions was implemented in order to reduce the
      ratios of three quality indicators: non-planned extubation (NPE), reintubation,
      and ventilator-associated pneumonia (VAP). VARIABLES OF INTEREST: NPE,
      reintubation and VAP ratios. RESULTS: A total of 232 patients were admitted, with
      a mean age of 49.5+/-17.8years; 119 (50.5%) were woman. The mean Simplified Acute
      Physiology Score (SAPS-3) was 49.8+/-17, and the mean Sequential Organ Failure
      Assessment (SOFA) score was 5.3+/-4.1. The mortality rate in the RICU was 38.7%.
      The standardized mortality ratio was 1.50 (95%CI: 1.20-1.84). An improved ratio
      was observed for reintubation and NPE indicators compared to the ratios of the
      previous 2011 cohort: 1.6% vs. 7% (P=.02) and 8.1 vs. 17 episodes per 1000 days
      of mechanical ventilation (P=.04), respectively. A worsened VAP ratio was
      observed: 18.4 vs. 15.1 episodes per 1000 days of mechanical ventilation (P=.5).
      CONCLUSIONS: Quality improvement is feasible with the identification of areas of
      opportunity and the implementation of strategies. Nevertheless, the
      implementation of a bundle of preventive measures in itself does not guarantee
      improvements.

PMID- 24661921
TI  - [Subarachnoid extravasation of intravenous contrast after arteriography in a
      patient with acute pulmonary thromboembolism].

PMID- 24661922
TI  - Invasive treatment for infrainguinal claudication has satisfactory 1 year outcome
      in three out of four patients: a population-based analysis from Swedvasc.
AB  - OBJECTIVES: In spite of recommendations advocating conservative best medical
      treatment, many patients with infrainguinal intermittent claudication (IC) are
      treated by invasive open and endovascular methods. This study aims to evaluate
      the incidence and 1-year results of all such treatments during 2009 in Sweden.
      METHODS: The design was a one-year follow-up through the Swedish Vascular
      Registry (Swedvasc) of all 775 patients from the Swedish population of 10 million
      inhabitants in whom 843 invasive infrainguinal procedures (796 index procedures
      and 47 secondary procedures) were performed for IC in 2009. Index procedures were
      open surgery in 290 (37%) patients, bilateral in nine cases, giving a total of
      299 limbs, endovascular treatment in 447 (58%) patients, bilateral in 10, giving
      a total of 457 limbs, and hybrid treatment in 38 (5%) patients, bilateral in two
      cases, giving a total of 40 limbs. Data were analysed both with regard to the
      number of patients (775) and the number of procedures (843). Clinical outcome was
      calculated from patient-reported leg function (unchanged, improved, deteriorated)
      and whether amputation had been necessary or death had occurred. Patent
      reconstruction at 1 year was also counted as improvement. RESULTS: Improvement at
      1 year was seen in 567 (73.2%) patients, (225 [77.6%] in the open surgery group,
      320 [71.6%] in the endovascular treatment group, and 22 [57.9%] in the hybrid
      treatment group). No significant difference was found between the open surgery
      and endovascular treatment groups comprising 737/775 patients (p = .350). Hybrid
      treatment gave significantly worse results (p = .046). Fifty-seven (7.3%)
      patients reported unchanged limb function and 32 (4.1%) patients reported
      deterioration. Within 30 days two patients died and one patient underwent
      amputation. Within 1 year 10 patients underwent 11 amputations: five (1.7%) in
      the open surgery group, three (0.6%) in the endovascular treatment group, and two
      (7.5%) in the hybrid treatment group; one underwent bilateral amputation (p =
      .07). Twenty-two patients died: 10 (3.4%) in the open surgery group, 12 (2.7%) in
      the endovascular treatment group and none in the hybrid treatment group (p =
      .465). CONCLUSIONS: Reported improvement at 1 year was 73.2% in patients
      invasively treated for infrainguinal IC. Patients reporting an unchanged or
      deteriorated clinical state are a considerable clinical challenge. Further
      studies to determine whether or not invasive treatment of infrainguinal IC is
      appropriate are justified.

PMID- 24661923
TI  - Supersize me: how whole-genome sequencing and big data are transforming
      epidemiology.
AB  - In epidemiology, the identification of 'who infected whom' allows us to quantify
      key characteristics such as incubation periods, heterogeneity in transmission
      rates, duration of infectiousness, and the existence of high-risk groups.
      Although invaluable, the existence of many plausible infection pathways makes
      this difficult, and epidemiological contact tracing either uncertain,
      logistically prohibitive, or both. The recent advent of next-generation
      sequencing technology allows the identification of traceable differences in the
      pathogen genome that are transforming our ability to understand high-resolution
      disease transmission, sometimes even down to the host-to-host scale. We review
      recent examples of the use of pathogen whole-genome sequencing for the purpose of
      forensic tracing of transmission pathways, focusing on the particular problems
      where evolutionary dynamics must be supplemented by epidemiological information
      on the most likely timing of events as well as possible transmission pathways. We
      also discuss potential pitfalls in the over-interpretation of these data, and
      highlight the manner in which a confluence of this technology with sophisticated
      mathematical and statistical approaches has the potential to produce a paradigm
      shift in our understanding of infectious disease transmission and control. 

PMID- 24661924
TI  - Screening for adrenal suppression in children with inflammatory bowel disease
      discontinuing glucocorticoid therapy.
AB  - BACKGROUND: Pharmacological doses of corticoids may result in adrenal suppression
      but with individual sensitivity. In paediatric inflammatory bowel disease (IBD),
      glucocorticoids are needed in the majority of the patients but there are less
      studies related to tapering off the drugs. The objective of this study was to
      estimate the frequency of adrenal insufficiency in children with IBD that were at
      the end of their systemic glucocorticoid therapy course. METHODS: The study was a
      retrospective case series of 59 consecutive paediatric IBD patients (median age
      14.1 years; Crohn's disease n = 22, ulcerative colitis n = 26, unclassified
      colitis n = 11) that were on oral prednisolone therapy about to be discontinued.
      The study patients were treated in a tertiary university hospital setting. Serum
      morning cortisol was measured with Immulite 2000 cortisol kit. Values < 20 nmol/l
      are undetectable and indicate adrenal suppression, values > 69 nmol/l are
      considered to represent normal basal secretion. RESULTS: The morning cortisol was
      below the reference range in 20% of the patients and undetectable in 10%. Low
      cortisol levels associated with higher daily glucocorticoid doses (median 7.2
      mg/m(2) vs. 3.0 mg/m(2) in patients with normal cortisol levels, p < 0.05) and
      with the long duration of the treatment (median 11 months vs. 4 months, p <
      0.05). Patients with undetectable cortisol levels recovered within few weeks
      (median 5.6 weeks). CONCLUSIONS: In paediatric IBD prolonged courses of
      glucocorticoids are frequent due to the steroid-dependent nature of the disease
      in a considerable proportion of patients. Adrenal suppression may occur in at
      least one fifth of the patients despite slowly tapering off the glucocorticoids.
      Notably, this is based on a set of serum cortisol measurements by request of
      experienced clinicians. All paediatric IBD patients receiving conventional doses
      of oral glucocorticoids should be subjected to screening for adrenal suppression
      when anticipated discontinuation of the drug.

PMID- 24661925
TI  - Report on the 25th Annual Meeting of the Japanese Association for Developmental
      and Comparative Immunology (JADCI), August 26 (Monday) to 28 (Wednesday), 2013,
      the 50th Year Commemorative Building of Okayama University of Science, Okayama
      700-0005, Japan (Local Organizer, Nobuhiko Asada).

PMID- 24661926
TI  - Modification of a synthetic LPS-binding domain of anti-lipopolysaccharide factor
      from shrimp reveals strong structure-activity relationship in their antimicrobial
      characteristics.
AB  - Anti-lipopolysaccharide factor (ALF) is a small protein with broad-spectrum
      antimicrobial activities and certain antiviral property. Its putative
      lipopolysaccharide (LPS) binding domain was deduced to be important for its
      activities. However, there is still no report revealing how the structure of the
      LPS-binding domain affects its biological function until now. In the present
      study, we designed and synthesized a peptide corresponding to the LPS-binding
      domain of ALF from the Chinese shrimp (designated as FcALF-LBDc) and its
      structure-modified isoforms in order to analyze the relationship between its
      structure and antimicrobial activities. Results showed that FcALF-LBDc exhibited
      apparent antibacterial activities against both Gram-negative bacteria Escherichia
      coli and Vibrio anguillarum and Gram-positive bacteria Micrococcus luteus and
      Micrococcus lysodeikticus with MIC ranges of 32-64, 2-4, 1-2, and 32-64MUM,
      respectively. The disulfide loop and the basic amino acids in the LPS-binding
      domain (LBD) of ALF played key roles in its antibacterial activities. In
      addition, FcALF-LBDc could reduce the propagation of white spot syndrome virus
      (WSSV) in vivo, and its lysine residue is indispensable for its antiviral
      property. This is the first attempt to testify the effects of the sequence
      features of the LPS-binding domain on its antimicrobial activities. 

PMID- 24661927
TI  - Multicriteria Evaluation of Classical Swine Fever Control Strategies Using the
      Choquet Integral.
AB  - An outbreak of the highly contagious animal disease classical swine fever (CSF)
      requires the selection of an optimal control strategy. The choice of a control
      strategy is a decision process depending on different aspects. Besides
      epidemiology, economic and ethical/social aspects must be taken into account. In
      this study, multicriteria decision-making (MCDM) was used to evaluate six control
      strategies for two regions with different farm densities. A strategy including
      only the minimum EU control measures and the traditional control strategy based
      on preventive culling were compared to alternative control strategies using
      emergency vaccination and/or rapid PCR testing ('emergency vaccination', 'test to
      slaughter', 'test to control' and 'vaccination in conjunction with rapid
      testing'). The MACBETH approach was used in order to assess the three main
      criteria (epidemiology, economics and ethical/social aspects). Subcriteria with
      both quantitative and qualitative performance levels were translated into a
      normalized scale. The Choquet integral approach was adopted to obtain a ranking
      of the six CSF control strategies based on the three main criteria, taking
      interactions into account. Three different rankings of the importance of the main
      criteria, which were to reflect the potential perceptions of stakeholders, were
      examined. Both the region under investigation and the ranking of the main
      criteria had an influence on the 'best' choice. Alternative control strategies
      were favourable to the minimum EU control and the traditional control measures
      independent of the farm density. Because the choice of the 'best' control
      strategy does not solely depend on the epidemiological efficiency, MCDM can help
      to find the best solution. Both MACBETH and the Choquet integral approach are
      feasible MCDM approaches. MACBETH only needs a qualitative evaluation and is
      therefore a comparatively intuitive approach. The Choquet integral does not only
      take the importance of the criteria into account but also the interaction between
      them. 

PMID- 24661928
TI  - Fabry disease presenting as apical left ventricular hypertrophy in a patient
      carrying the missense mutation R118C.
AB  - Anderson-Fabry disease is an X-linked lysosomal storage disorder caused by
      abnormalities of the GLA gene, which encodes the enzyme alpha-galactosidase A. A
      deficiency of this enzyme leads to the lysosomal accumulation of
      glycosphingolipids, which may cause left ventricular hypertrophy that is
      typically concentric and symmetric. We present the case of a 60-year-old woman
      with symptoms of dyspnea, atypical chest pain and palpitations, in whom a
      transthoracic echocardiogram revealed an apical variant of hypertrophic
      cardiomyopathy. Analysis of specific sarcomeric genetic mutations was negative.
      The patient underwent a screening protocol for Anderson-Fabry disease, using a
      dried blood spot test, which was standard at our institution for patients with
      left ventricular hypertrophy. The enzymatic activity assay revealed reduced alpha
      galactosidase A enzymatic activity. Molecular analysis identified a missense
      point mutation in the GLA gene (p.R118C). This case report shows that Anderson
      Fabry disease may cause an apical form of left ventricular hypertrophy. The
      diagnosis was only achieved because of systematic screening, which highlights the
      importance of screening for Anderson-Fabry disease in patients with unexplained
      left ventricular hypertrophy, including those presenting with more unusual
      patterns, such as apical variants of left ventricular hypertrophy. This case also
      supports the idea that the missense mutation R118C is indeed a true pathogenic
      mutation of Anderson-Fabry disease. 

PMID- 24661929
TI  - Mycoplasma genitalium promotes epithelial crossing and peripheral blood
      mononuclear cell infection by HIV-1.
AB  - BACKGROUND: Mycoplasma genitalium co-infection in HIV-infected individuals has
      been reported to increase the shedding of HIV in the urogenital region of
      females. To better understand this relationship, we investigated the influence of
      M. genitalium on the transmission and replication of HIV using an in vitro model.
      METHODS: The Transwell co-culture system was employed to assess the crossing of
      an endocervical cell barrier by HIV-1. Immunocytochemistry and confocal
      microscopy were used to assess the distribution of the nectin-1 molecule on M.
      genitalium-infected epithelial cells of the End1/E6E7 endocervical cell line,
      grown as monolayers in the insert wells. Peripheral blood mononuclear cells
      (PBMC) were cultured in the bottom wells to assess the effects of M. genitalium,
      passing through the semipermeable culturing membrane, on subsequent HIV infection
      of susceptible target cells. RESULTS: Infection of the endocervical cells with
      the adhesion-positive M. genitalium G37 strain (wild-type) significantly elevated
      the passage of HIV across the epithelial cell barrier relative to HIV transfer
      across endocervical cells infected with the adhesion-negative M. genitalium JB1
      strain. Immunostaining of the M. genitalium-G37-infected epithelial cells
      disclosed capping and internalization of the junctional regulatory protein nectin
      1, in association with reduced transepithelial resistance (TER) in the cell
      monolayer. When PBMC were cultured beneath insert wells containing M. genitalium
      G37-infected epithelial cell monolayers, we observed significantly enhanced
      infectivity and replication of HIV added afterward to the cultures. CONCLUSIONS:
      M. genitalium influences events on both sides of a cultured mucosal epithelial
      monolayer: (1) by infecting the epithelial cells and reducing the integrity of
      the barrier itself, and (2) by activating HIV target cells below it, thereby
      promoting HIV infection and progeny virus production.

PMID- 24661930
TI  - Treatment of human papillomavirus infection with interferon alpha and ribavirin
      in a patient with acquired aplastic anemia.
AB  - Genital warts caused by human papillomavirus (HPV) are the most frequent sexually
      transmitted infection. We describe a case of severe perianal and genital HPV
      infection in a patient with acquired aplastic anemia, unresponsive to traditional
      therapies and treated effectively with a combination of interferon and ribavirin.

PMID- 24661931
TI  - Clinical profile and improving mortality trend of scrub typhus in South India.
AB  - BACKGROUND: Scrub typhus, a bacterial zoonosis caused by Orientia tsutsugamushi,
      may cause multiorgan dysfunction syndrome (MODS) and is associated with
      significant mortality. This study was undertaken to document the clinical and
      laboratory manifestations and complications and to study time trends and factors
      associated with mortality in patients with scrub typhus infection. METHODS: This
      retrospective study, done at a university teaching hospital, included 623
      patients admitted between 2005 and 2010 with scrub typhus. The diagnosis was
      established by a positive IgM ELISA and/or pathognomonic eschar with PCR
      confirmation where feasible. The clinical and laboratory profile, course in
      hospital, and outcome were documented. Factors associated with mortality were
      analyzed using multivariate logistic regression analysis. RESULTS: The most
      common presenting symptoms were fever (100%), nausea/vomiting (54%), shortness of
      breath (49%), headache (46%), cough (38%), and altered sensorium (26%). An eschar
      was present in 43.5% of patients. Common laboratory findings included elevated
      transaminases (87%), thrombocytopenia (79%), and leukocytosis (46%). MODS was
      seen in 34% of patients. The overall case-fatality rate was 9.0%. Features of
      acute lung injury were observed in 33.7%, and 29.5% required ventilatory support.
      On multivariate analysis, shock requiring vasoactive agents (relative risk (RR)
      10.5, 95% confidence interval (CI) 4.2-25.7, p<0.001), central nervous system
      (CNS) dysfunction (RR 5.1, 95% CI 2.4-10.7, p<0.001), and renal failure (RR 3.6,
      95% CI 1.7-7.5, p=0.001) were independent predictors of mortality. Over 4 years,
      a decreasing trend was observed in the mortality rate. CONCLUSIONS: Scrub typhus
      can manifest with potentially life-threatening complications such as lung injury,
      shock, and meningoencephalitis. MODS occurred in a third of our patients. The
      overall case-fatality rate was 9%, with shock, renal failure, and CNS associated
      with a higher mortality.

PMID- 24661932
TI  - Dirofilaria repens in the Russian Federation: current epidemiology, diagnosis,
      and treatment from a federal reference center perspective.
AB  - BACKGROUND: Dirofilariasis is an emerging zoonotic infection in which the human
      serves as an accidental host. Russia has been one of the most important endemic
      regions worldwide for Dirofilaria repens, the most prevalent Dirofilaria species
      in Europe. METHODS: Based on a cohort of patients at the Rostov Medical
      University, we provide an epidemiological description of 236 human cases,
      reporting common clinical symptoms and treatment options for D. repens infections
      in humans. The performance of a non-commercial immunoassay was validated in a
      diagnostic sub-study (diagnostic accuracy 83%). Data from mosquito surveys and
      cross-sectional surveys of dogs, the main reservoir of D. repens, are also
      presented. RESULTS: Results showed important variations in prevalence depending
      on sex, geographic location, and the use of dogs (professional service dogs or
      pets). CONCLUSIONS: The particularly high prevalence of Dirofilaria infection in
      professional dogs used in the police force and armed forces poses a particular
      problem, since these dogs may serve as epidemiologically important amplifiers
      within the region of the former Soviet Union.

PMID- 24661933
TI  - [Autoimmune chronic hepatitis presenting as prurigo nodularis].

PMID- 24661934
TI  - [Endoscopic submucosal dissection in the treatment of recurrence of a laterally
      spreading tumor-granular (LST-G) mixed-type rectal neoplasm with severe
      submucosal fibrosis secondary to two prior mucosectomies].

PMID- 24661935
TI  - Genetic susceptibility and gastric cancer risk: the importance of meta-analyses
      as a statistical tool.
AB  - Gastric cancer (GC) is a complex disease and a worldwide health burden due to its
      high prevalence and poor prognosis. A deeper knowledge of the factors involved in
      the development and progression of GC could help to identify subpopulations at
      risk that therefore require surveillance or early treatment strategies. Current
      research is based on the study of genetic variants that confer a higher risk of
      GC and their interactions with environmental exposure. Recently, meta-analysis
      has emerged as an important statistical method involving pooling of data from
      individual association studies to increase statistical power and obtain more
      conclusive results. Given the importance of chronic inflammation in the process
      of gastric carcinogenesis, the present article reviews the most recent meta
      analyses of the contribution of cytokine gene polymorphisms to GC risk. 

PMID- 24661936
TI  - What we have accomplished and what we can achieve.

PMID- 24661937
TI  - An ounce of prevention is worth a pound of cure.

PMID- 24661938
TI  - A common factor suppresses thickening in young women with malar area port wine
      stains and delays low density lipoprotein elevation: is it estrogen?
AB  - Port wine stains in the malar area of the face can develop thickening in early
      adult life. We began a study with a hypothesis that this thickening can be
      associated with elevation of low density lipoprotein. In a retrospective review,
      we divided 53 subjects with malar port wine stains into 4 groups, adults 25-39
      years of age with thickening, that age group without thickening, adults 40+ years
      of age with thickening, and that age group without thickening. Low density
      lipoprotein levels in the subjects were compared to age and sex matched controls
      randomly selected from the general Dermatology clinic. The younger subjects with
      thickening demonstrated significantly higher low density lipoprotein levels than
      their controls (p .0082) and without thickening lower low density lipoprotein
      levels than their controls with great significance (p .00058). The subjects
      without thickening also consisted mainly of women. The low density lipoprotein
      levels in the older age groups, whether thickened or not, demonstrated no
      significant difference in low density lipoprotein levels between subjects and
      controls. This led to a new hypothesis that there is a factor in a subgroup of
      young adult women with malar port wine stains that suppresses thickening and
      delays the elevation of low density lipoprotein and that this factor might be
      estrogen. The implications of this hypothesis are that it could define a marker
      for a subset of the population that might be protected from the diseases
      associated with early elevation of low density lipoprotein and provide a source
      of cutaneous tissue for studying the basic science of this protection (although
      limited by cosmetic considerations). Future laboratory research to test the new
      hypothesis might include testing blood of women with malar port wine stains with
      or without thickening for estrogen and other sex hormones. It might also include
      skin biopsies to study receptors for estrogen, other sex hormones, and angiogenic
      factors in malar port wine stains with or without thickening. Future clinical
      research might include a long term prospective project to study the development
      of low density lipoprotein related diseases in women with malar port wine stains
      with or without thickening over years.

PMID- 24661939
TI  - Biological basis of neuroprotection and neurotherapeutic effects of Whole Body
      Periodic Acceleration (pGz).
AB  - Exercise is a well known neuroprotective and neurotherapeutic strategy in animal
      models and humans with brain injury and cognitive dysfunction. In part, exercise
      induced beneficial effects relate to endothelial derived nitric oxide (eNO)
      production and induction of the neurotrophins; Brain Derived Neurotrophic Factor
      (BDNF) and Glial Derived Neurotrophic Factor (GDNF). Whole Body Periodic
      Acceleration (WBPA (pGz), is the motion of the supine body headward to footward
      in a sinusoidal fashion, at frequencies of 100-160 cycles/min, inducing pulsatile
      shear stress to the vascular endothelium. WBPA (pGz) increases eNO in the
      cardiovascular system in animal models and humans. We hypothesized that WBPA
      (pGz) has neuroprotective and neurotherapeutic effects due to enhancement of
      biological pathways that include eNOS, BDNF and GDNF. We discuss protein
      expression analysis of these in brain of rodents. Animal and observational human
      data affirm a neuroprotective and neurotherapeutic role for WBPA (pGz). These
      findings suggest that WBPA (pGz) in addition to its well known beneficial
      cardiovascular effects can be a simple non-invasive neuroprotective and
      neurotherapeutic strategy with far reaching health benefits. 

PMID- 24661940
TI  - A pilot investigation of "metaphor blindness" in a college student population.
AB  - Previous research from our group suggests that patients with lesions in the left
      inferior parietal lobule (IPL)-which is concerned with abstract numerical
      cognition and cross-modal association (which is consistent with its strategic
      location at the crossroads between the temporal, parietal and occipital lobes)
      have difficulty understanding proverbs and metaphors (Ramachandran and Hubbard,
      2001). In the current pilot investigation, we report "metaphor blindness" in a
      college student population; that is, either the complete inability or difficulty
      for otherwise intellectually non-challenged individuals to comprehend metaphors
      of language. Participants (N=205) read 12 metaphorical ("The detective jumped at
      the clue") and 12 literal ("The accident was a fall") sentences and had to decide
      whether the sentences conveyed a metaphorical or literal meaning. The mean
      accuracy for these metaphorical sentences was 11.0 (SD=2.3; RNG=0-12); the mean
      accuracy for literal sentences was 7.2 (SD=1.8; RNG=2-10). We found that 5% of
      participants (11/205) were unable or had difficulty understanding metaphors
      (i.e., were statistical outliers), while their score for literal sentences felt
      within a normal statistical range M=8.3 (SD=2.3; RNG=5-10). Follow-up control
      procedures were conducted in order to help ascertain that the results were not
      due to low verbal IQ and task difficulty. Likewise, none of the "metaphor blind"
      participants reported any psychiatric or neurological histories that would impair
      language comprehension, including strokes, brain injuries, language problems
      dyslexia, and signs of late language onset. The results are very preliminary and
      future studies are needed to confirm these findings. We suggest that brain
      modules may be specialized even for subtle functions like metaphor and their
      formation in embryogenesis may be controlled by small handfuls of genes whose
      expression can go awry--as in "metaphor blindness".

PMID- 24661941
TI  - Does khat chewing increases the risk of Mycobacterium tuberculosis infection by
      macrophage immune modulation?
AB  - Drug abuse is a serious problem associated with different pathological outcomes
      including modulating the immune system. Drug abuse is rising in Saudi Arabia and
      so as TB, a disease of worldwide significance, caused by immunological modulation
      in the host system. Khat chewing is a common practice in Arabian Peninsula which
      is now gaining momentum in other parts of the world. It is considered as an
      addiction. It has been associated with different adverse outcomes such as
      periodontitis, oral leukoplakia and oral cancer and also has shown to promote
      apoptotic cell death through cysteine proteases. The active ingredient of khat,
      cathinone is shown to have immunomodulatory effect. In principle, this leads to
      enhanced susceptibility to various infections. The present study is designed to
      delineate the mechanism of immunomodulation produced by khat/cathinone in
      human/mouse macrophage. Further, this activity will be evaluated both in vivo and
      in vitro in response to infection with Mycobacterium smegmatis to get an insight
      if there exists a co relation between the Mycobacterium tuberculosis infection
      and khat chewing. 

PMID- 24661942
TI  - Determinants of respiratory pump function in patients with cystic fibrosis.
AB  - Respiratory failure constitutes the major cause of morbidity and mortality in
      patients with Cystic Fibrosis (CF). Respiratory failure could either be due to
      lung parenchyma damage or to insufficiency of the respiratory pump which consists
      of the respiratory muscles, the rib cage and the neuromuscular transmission
      pathways. Airway obstruction, hyperinflation and malnutrition have been
      historically recognised as the major determinants of respiratory pump dysfunction
      in CF. Recent research has identified chronic infection, genetic predisposition,
      dietary and pharmaceutical interventions as possible additional determinants of
      this impairment. Furthermore, new methodological approaches in assessing
      respiratory pump function have led to a better understanding of the pathogenesis
      of respiratory pump failure in CF. Finally, respiratory muscle function could be
      partially preserved in CF patients with structured interventions such as aerobic
      exercise, inspiratory muscle training and non-invasive ventilation and CF
      patients could consequently be relatively protected from respiratory fatigue and
      respiratory failure.

PMID- 24661943
TI  - Brominated flame retardants in the urban atmosphere of Northeast China:
      concentrations, temperature dependence and gas-particle partitioning.
AB  - 57 pairs of air samples (gas and particle phases) were collected using a high
      volume air sampler in a typical city of Northeast China. Brominated flame
      retardants (BFRs) including 13 polybrominated diphenyl ethers (PBDEs, including
      BDEs 17, 28, 47, 49, 66, 85, 99, 100, 138, 153, 154, 183, and 209) and 9
      alternative BFRs (p-TBX, PBBZ, PBT, PBEB, DPTE, HBBZ, gamma-HBCD, BTBPE, and
      DBDPE) were analyzed. The annual average total concentrations of the 13 PBDEs and
      the 9 alternative BFRs were 69 pg/m(3) and 180 pg/m(3), respectively. BDE 209 and
      gamma-HBCD were the dominant congeners, according to the one-year study. The
      partial pressure of BFRs in the gas phase was significantly correlated with the
      ambient temperature, except for BDE 85, gamma-HBCD and DBDPE, indicating the
      important influence of ambient temperature on the behavior of BFRs in the
      atmosphere. It was found that the gas-particle partitioning coefficients (logKp)
      for most low molecular weight BFRs were highly temperature dependent as well. Gas
      particle partitioning coefficients (logKp) also correlated with the sub-cooled
      liquid vapor pressure (logPL(o)). Our results indicated that absorption into
      organic matter is the main control mechanism for the gas-particle partitioning of
      atmospheric PBDEs.

PMID- 24661944
TI  - Enhanced delivery of artemisinin and its analogues to cancer cells by their
      adducts with human serum transferrin.
AB  - Artemisinin (ART) and its analogues, such as dihydroartesunate (DHA) and
      artesunate (ATS), are sesquiterpene lactones with anticancer activities.
      Transferrin (Tf) receptor is frequently overexpressed in cancer cells. In order
      to improve the delivery and the anticancer activity of ART and its analogues,
      adducts of Tf with ART, DHA or ATS were fabricated by simply combining ART, DHA
      or ATS with Tf. Increased antitumor effects of these adducts were observed on
      human liver hepatocellular carcinoma (HepG2) and lung adenocarcinoma (A549)
      cells. Meanwhile, only a low level of toxic effect was observed on normal human
      liver cells (HL-7702). Improved cellular uptake of ATS-Tf adduct compared to ATS
      alone was confirmed by HPLC analysis. UV-vis, fluorescence spectroscopy and
      docking study further confirmed the formation of the adducts with relatively high
      binding constants at neutral pH (7.4*10(4), 4.2*10(5) and 3.4*10(5)M(-1), for ART
      Tf, DHA-Tf and ATS-Tf, respectively, at pH 7.4). However, the adducts became less
      stable with reduced binding constants under an acidic condition (2.6*10(4),
      1.9*10(4) and 1.7*10(4)M(-1), for ART-Tf, DHA-Tf and ATS-Tf, respectively, at pH
      5.5). A possible mechanism of the anticancer effect by these adducts was
      proposed. The short term and long term stability of ART-Tf in the presence of
      human serum albumin (HSA) was also studied. Our results showed that adducts of
      ART and its analogues with Tf, especially ATS-Tf and DHA-Tf, have significant
      anticancer effects to cancer cells, with minimal side effects on normal cells,
      therefore, are promising as potential novel anticancer agents.

PMID- 24661945
TI  - Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates
      high-fat diet induced hypertriglyceridemia and hyperglycemia in mice.
AB  - This study was conducted to evaluate the effects of umbelliferone (UF) and 4
      methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and
      hyperglycemia in mice. The mice were assigned to normal control, high-fat
      control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat
      diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12weeks. Both UF and
      mUF significantly decreased plasma triglyceride, free fatty acid and glucose
      levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate
      phosphohydrolase activity and significantly increased plasma adiponectin levels
      and hepatic fatty acid beta-oxidation activity compared with the high-fat control
      group. UF and mUF improved glucose intolerance and hepatic steatosis in the high
      fat fed mice. Long-term high-fat diet intake induced an increase in hepatic
      CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and
      suppressed superoxide dismutase and glutathione peroxidase activities, which were
      reversed by UF and mUF supplementation. These results indicate that UF and mUF
      similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating
      hepatic lipid metabolism and the antioxidant defense system along with increasing
      adiponectin levels. 

PMID- 24661946
TI  - Healthy F-16 pilots show no evidence of exposure to tri-ortho-cresyl phosphate
      through the on-board oxygen generating system.
AB  - About 18% of fighter pilots complain of ill symptoms that begin during flight and
      persist for days. A possible source of toxicity is the air supplied through the
      on board oxygen generating system. The air passes through the jet engine before
      it is enriched for oxygen and breathed through an oxygen mask. While in the jet
      engine, the air can become contaminated with jet engine lubricating oil. A
      potentially toxic component in jet engine oil is tri-ortho-cresyl phosphate
      (TOCP), which is metabolically activated to the highly reactive cresyl saligenin
      phosphate. The cresyl saligenin phosphate reacts with butyrylcholinesterase
      (BChE) to make a covalent adduct on serine 198. The purpose of this work was to
      determine whether the blood of healthy, active-duty F-16 pilots has measurable
      levels of the cresyl phosphate adduct. BChE was immunopurified from 0.5ml plasma
      by binding to immobilized monoclonal mAb2. BChE protein was released with acetic
      acid, digested with pepsin and analyzed by LC-MS/MS on the 5600 Triple TOF mass
      spectrometer. Positive controls for quantifying the limit of detection were
      plasma samples containing known amounts of cresyl saligenin phosphate treated
      plasma. The cresyl phosphate adduct eluted at 31.3min with an observed parent ion
      mass of 966.4m/z and characteristic daughter ions 778.3, 673.3, and 602.3m/z.
      Control experiments demonstrated that as little as 0.1% of the 1-2MUg BChE
      recovered from 0.5ml plasma could be detected as the cresyl phosphate adduct on
      peptide FGES198AGAAS. Mass spectrometry analysis of plasma from fifteen healthy F
      16 pilots showed that none had evidence of exposure to TOCP. It was concluded
      that the on-board oxygen generating system, when operating properly, did not
      deliver tri-ortho-cresyl phosphate in the oxygen supply. 

PMID- 24661947
TI  - Molecular mechanisms of hyperthermia-induced apoptosis enhanced by
      docosahexaenoic acid: implication for cancer therapy.
AB  - To develop a non-toxic enhancer for hyperthermia-induced cell death as a
      potential cancer treatment, we studied the effect and mechanism of
      docosahexaenoic acid (DHA) on hyperthermia-induced apoptosis. Treatment with
      20MUM DHA and 44 degrees C for 10min induced significant apoptosis, increased
      intracellular reactive oxygen species (ROS), and caspase-3 activation in U937
      cells, but heat or DHA alone did not induce notable apoptosis. Decreased
      mitochondrial transmembrane potentials were dramatically increased by the
      combined treatment, accompanied by increased pro-apoptotic Bcl-2 family protein
      tBid, and decreased anti-apoptotic Bcl-2 and Bcl-xL. Combined hyperthermia-DHA
      treatment induced significant phosphorylation of protein kinase C (PKC)-delta (p
      PKC-delta), and apoptosis in a DHA dose-dependent manner. Using both 20MUM DHA
      and 44 degrees C for 10min induced significant PKC-delta cleavage and its
      translocation to mitochondria. These results were also seen in HeLa cells.
      However, MAPKs and Akt were not affected by the treatment. In conclusion, DHA
      enhances hyperthermia-induced apoptosis significantly via a mitochondria-caspase
      dependent pathway; its underlying mechanism involves elevated intracellular ROS,
      mitochondria dysfunction, and PKC-delta activation. 

PMID- 24661948
TI  - Diagnostic imaging in dermatology: utility of PET-CT in cutaneous melanoma.
AB  - Malignant melanoma accounts for 5% of all malignant skin tumors and its incidence
      is increasing. In the natural course of melanoma, tumors grow locally and can
      spread via the lymph system or the blood. Because survival is directly related to
      the stage of the disease at diagnosis, early detection (secondary prevention) has
      an impact on prognosis. Positron emission tomography (PET) is a nuclear medicine
      technique that generates images using molecules labeled with positron-emitting
      isotopes. The most widely used molecule is fluorodeoxyglucose (FDG). Because of
      the elevated glycolytic rate in tumor cells, which results in increased FDG
      uptake, greater quantities of FDG become trapped in tumor cells, enabling
      external detection. Today, most PET scanners are multimodal PET-computed
      tomography (CT) scanners, which provide more detailed information by combining
      morphological information with functional PET findings. The possible utility of
      PET-CT in patients with malignant melanoma is a subject of debate. Various
      questions have been raised: when the scan should be performed, whether PET-CT has
      advantages over conventional diagnostic methods, and whether PET-CT provides a
      real benefit to patients. In this review of the literature, we will analyze each
      of these questions. 

PMID- 24661949
TI  - Informed consent in dermatology: an update.
AB  - Spanish legislation recognizes patients' right to be informed about various
      aspects of their illness and to make autonomous decisions regarding diagnosis and
      treatment. As dermatologists, we need to become familiar with this legislation,
      heed its stipulations, and implement them in our practice.

PMID- 24661950
TI  - Fibrinogen, an endogenous ligand of Toll-like receptor 4, activates monocytes in
      pre-eclamptic patients.
AB  - Pre-eclampsia (PE) remains the leading cause of pregnancy-associated mortality
      and morbidity, urging the need for a better understanding of its aetiology and
      pathophysiological progression. A key characteristic of PE is a systemic,
      exaggerated, inflammatory condition involving abnormal cytokine levels in serum,
      altered immune cell phenotype and Th1/Th2-type immunological imbalance. However,
      it is unknown how this heightened inflammatory condition manifests. We previously
      reported increased expression of the lipopolysaccharide receptor, Toll-like
      receptor 4 (TLR4), on monocytes from PE patients compared with normotensive,
      pregnant patients (NP). This upregulation of TLR4 on PE monocytes was accompanied
      by a hyper-responsiveness to bacterial TLR4 ligands. To determine whether non
      microbial, endogenous TLR4 ligands also activate monocytes from PE patients, we
      investigated the expression of host-derived TLR4 ligands and the response of
      monocytes to these endogenous ligands. Plasma levels of fibrinogen - but not
      fibronectin or heparan sulphate - were higher in PE patients than in NP. Exposure
      to fibrinogen was associated with significantly increased production of
      inflammatory cytokines by monocytes from PE patients. Interestingly, this effect
      was not observed with NP monocytes. Our findings suggest that the fibrinogen-TLR4
      axis might play an important role in the atypical activation of monocytes
      observed in PE patients that may contribute to the exaggerated inflammatory
      condition. 

PMID- 24661952
TI  - Auricular chondro-perichondrial graft in the reconstruction of the lower eyelid.

PMID- 24661951
TI  - Therapeutic effects of functional orthodontic appliances on cervical spine
      posture: a retrospective cephalometric study.
AB  - INTRODUCTION: Interactions between the cervical spine and the stomatognathic
      system have been discussed in literature. The present study was conducted to
      investigate whether, and to what extent, orthodontically induced mandibular
      advancement produces changes in cervical spine posture. Furthermore, possible
      appliance-specific effects should be distinguished. MATERIAL AND METHODS: The
      cephalograms of 64 patients with skeletal class II were analysed before and after
      mandibular advancement. Linear and angular cephalometric parameters were
      identified to define the position of the atlanto-occipital and atlantoaxial
      joints. The total example was divided into two subgroups (comprising 32
      individuals each) according to the employed appliance: activator versus bite-jump
      appliance (BJA). Student's t-test and analysis of covariance were used for
      statistical analysis. RESULTS: Overall, a significant straightening of the
      cervical spine was observed during the treatment. This conclusion is based on
      changes of Chamberlain (p = 0.0055), CVT (p = 0.0003), OPT (p < 0.0001), Redlund
      Johnell/Petersson (p < 0.0001), McGregor-mC2 (p = 0.0333) and AT-FH (p = 0.0445).
      Improvements in occipitoatlantal dislocation were also observed in the total
      sample. Appliance-specific changes were found in the activator subgroup for a
      number of linear parameters (Chamberlain, McGregor, CVT, OPT, Redlund
      Johnell/Petersson). In contrast, only two linear parameters (OPT and Powers
      ratio) revealed statistically significant changes in the BJA subgroup.
      CONCLUSIONS: During skeletal class II treatment the position of upper cervical
      spine changes. In the activator subgroup the observed effects were more
      pronounced than those in the BJA subgroup. Further studies including a control
      group comprised with non-treated class II patients are needed to assess whether
      these effects may be caused directly by the appliances irrespective of growth.

PMID- 24661953
TI  - Sun protection in children: realities and challenges.
AB  - One of the main goals of all skin cancer prevention campaigns is to protect
      children from ultraviolet radiation. However, little is known about how sun
      exposure risks differ between adults and children or about how these risks are
      best managed. Children's skin is more susceptible to sun damage for a number of
      reasons, including certain anatomical and functional aspects in children under 2
      years of age and habits that predispose to greater sun exposure during the first
      2 decades of life. Oil-based emulsions containing inorganic filters appear to be
      safest sunscreens for children, although the addition of certain organic filters
      is necessary to achieve a sun protection factor of 50. Oxybenzone, and probably
      also octocrylene, should be avoided in sunscreens for children. Sunscreen use
      should be part of an overall sun protection strategy that includes avoidance of
      exposure to midday sun and the use of protective clothing and hats. The above
      considerations justify the implementation of primary prevention campaigns focused
      on sun protection education for children and the continuation of basic and
      epidemiological research into specific sun protection strategies and sunscreens
      for each age group. 

PMID- 24661954
TI  - Postsurgical contact dermatitis due to povidone iodine: a diagnostic dilemma.
AB  - We present 7 cases of postsurgical contact dermatitis due to povidone iodine. The
      diagnosis was based on the clinical manifestations, the history of exposure, the
      site of the lesions, and the results of patch tests. This type of dermatitis can
      develop in the area of surgery or at distant sites exposed to povidone iodine
      during the surgical intervention. Patch tests with 10% povidone iodine in
      petrolatum were positive in all patients. Based on the results of the same tests
      in a control group, we recommend the use of petrolatum rather than water as the
      vehicle for the diagnosis of this form of contact dermatitis. Repeated open
      application tests with a commercially available solution of povidone iodine were
      negative. We conclude that the presence of the solution under occlusion during
      surgery is necessary both for the symptoms to develop and for the diagnosis to be
      made. This condition may be underdiagnosed. 

PMID- 24661955
TI  - Study of idiopathic, exogenous photodermatoses, part II: photobiologic testing.
AB  - The second of this series describes the characteristics of 3 types of
      photobiologic studies: the light test, the photochallenge test, and the
      photopatch test. We explain how the tests are carried out, the expected results,
      and their clinical usefulness in various photodermatoses. These tests are needed
      before attempting to induce adaptation (skin hardening or light tolerance) in the
      most debilitating cases. 

PMID- 24661956
TI  - The use of systematic reviews in clinical trials and narrative reviews in
      dermatology: is the best evidence being used?
AB  - INTRODUCTION AND OBJECTIVES: Systematic reviews -the most comprehensive type of
      literature review-should be taken into account before a clinical trial or a
      narrative review on a topic is undertaken. The objective of this study was to
      describe the use of systematic reviews in clinical trials and narrative reviews
      in dermatology. MATERIAL AND METHODS: This was a descriptive cross-sectional
      study. We selected randomized clinical trials and narrative reviews from the
      dermatological clinical research journals identified as most important (according
      to impact factor) and from Actas Dermosifiliograficas, and studied the
      bibliographies to ascertain whether the authors made reference to existing
      systematic reviews and Cochrane reviews. RESULTS: Of the 72 clinical trials for
      which a systematic review was available, 24 (33.3%) cited at least 1 review;
      reference was made to relevant Cochrane reviews in 15.6% of cases and to non
      Cochrane reviews in 32%. In the case of the 24 narrative reviews for which a
      review was available, 10 (41.7%) cited at least 1 review; Cochrane reviews were
      cited in 20% and non-Cochrane reviews in 35.3%.In the case of Actas
      Dermosifiliograficas, very few clinical trials were found and the findings for
      narrative review articles were similar to those observed for the other journals.
      CONCLUSIONS: Systematic reviews are not often taken into account by the authors
      of clinical trials and narrative reviews and this may lead to redundant studies
      and publications. Authors appear to use Cochrane reviews even less than non
      Cochrane reviews and are therefore ignoring one of the main sources of available
      evidence.

PMID- 24661957
TI  - Fixed drug eruption due to etoricoxib in a patient with tolerance to celecoxib:
      the value of patch testing.

PMID- 24661958
TI  - Design and validation of a questionnaire for measuring perceived risk of skin
      cancer.
AB  - INTRODUCTION: A perceived risk of cancer encourages preventive behavior while the
      lack of such a perception is a barrier to risk reduction. There are no
      instruments in Spanish to measure this perceived risk and thus quantify response
      to interventions for preventing this disease at a population level. The aim of
      this study was to design and validate a self-administered questionnaire for
      measuring the perceived risk of skin cancer. MATERIAL AND METHODS: A self
      administered questionnaire with a visual Likert-type scale was designed based on
      the results of the analysis of the content of a survey performed in 100 patients
      in the Dr. Ladislao de la Pascua Skin Clinic, Distrito Federal Mexico, Mexico.
      Subsequently, the questionnaire was administered to a sample of 359 adult
      patients who attended the clinic for the first time. As no gold standard exists
      for measuring the perceived risk of skin cancer, the construct was validated
      through factor analysis. RESULTS: The final questionnaire had 18 items. The
      internal consistency measured with Cronbach alpha was 0.824 overall. In the
      factor analysis, 4 factors (denoted as affective, behavioral, severity, and
      susceptibility) and an indicator of risk accounted for 65.133% of the variance.
      CONCLUSIONS: The psychometric properties of the scale were appropriate for
      measuring the perception of risk in adult patients (aged 18 years or more) who
      attended the dermatology clinic.

PMID- 24661959
TI  - WITHDRAWN: Melatonin attenuates lung injury in a hind limb ischemia-reperfusion
      rat model.
AB  - This article has been withdrawn for editorial reasons because the journal will be
      published only in English. In order to avoid duplicated records, this article can
      be found at http://dx.doi.org/10.1016/j.rppnen.2014.01.010. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24661960
TI  - End-of-life care in COPD: a survey carried out with Portuguese pulmonologists.
AB  - INTRODUCTION: End-of-life (EoL) care is a major component in the management of
      patients with advanced COPD. Patient-physician communication is essential in this
      process. AIM: To evaluate the practice of Portuguese Pulmonologists in EoL
      communication and palliative care in COPD. METHODS: An on-line survey was sent to
      physicians affiliated to the Portuguese Pneumology Society. RESULTS: We obtained
      136 answers from 464 eligible participants (29.3%). About half of the physicians
      reported that they have rarely introduced EoL discussions with their COPD
      patients (48.5%). Most had never/rarely suggested decision-making on the use of
      invasive mechanical ventilation (68.4%). Discussions were described as occurring
      mostly during/after a major exacerbation (53.7%). Only 37.5% of participants
      reported treating dyspnoea with opioids frequently/always. Only 9.6% stated that
      they never/rarely treated anxiety/depression. Most participants perceive the
      discussion of EoL issues as being difficult/very difficult (89.0%). The reasons
      most frequently given were feeling that patients were not prepared for this
      discussion (70.0%), fear of taking away a patient's hope (58.0%) and lack of
      training (51.0%). CONCLUSION: Patient and medical staff EoL communication in COPD
      is still not good enough. Training in this area and the creation of formal
      protocols to initiate EoL have been identified as major factors for improvement.

PMID- 24661961
TI  - Mycobacteria, meet your messenger.

PMID- 24661962
TI  - Idiopathic granulomatous hypophysitis: comments and a disease registry.

PMID- 24661963
TI  - Dysfunctional sleep beliefs in Parkinson's disease: relationships with subjective
      and objective sleep.
AB  - Disturbed sleep is common in Parkinson's disease and has a detrimental impact on
      functioning and quality of life. While the progression of the disease contributes
      to the aetiology of sleep problems in Parkinson's disease, it is unknown whether
      an individual's beliefs and attitudes about sleep play a role. In this study we
      sought to investigate whether dysfunctional beliefs and attitudes about sleep
      could be related to subjective and objective measures of sleep disturbance in
      Parkinson's disease. Ninety-three patients with Parkinson's disease completed the
      Dysfunctional Beliefs and Attitudes about Sleep 16 item questionnaire, which
      comprises four domains: Expectations, Worry/Helplessness, Consequences and
      Medication. Patients also completed the Pittsburgh Sleep Quality Index
      questionnaire and Beck Depression Inventory-II. Patients wore actigraphy watches
      and completed sleep diaries for 2 consecutive weeks, recording measures of sleep
      disturbance including Sleep Onset and Offset, Wake After Sleep Onset, Sleep
      Efficiency, and Wake Bouts per hour. Greater dysfunctional beliefs and attitudes
      in the domains of Worry/Helplessness and Medication were associated with lower
      perceived sleep quality and greater depressive symptoms. However, no
      relationships were found between dysfunctional beliefs and attitudes about sleep
      and any objective actigraphic measure of sleep disturbance. These findings
      suggest that beliefs and attitudes about sleep in Parkinson's disease are
      associated with mood disturbance, rather than objective measures of sleep. Thus
      it is possible that interventions targeting mood may lead to more accurate
      perceptions of sleep and improved quality of life in Parkinson's disease
      patients. 

PMID- 24661964
TI  - Radial and vertical distributions of radiocesium in tree stems of Pinus
      densiflora and Quercus serrata 1.5 y after the Fukushima nuclear disaster.
AB  - The radial and vertical distributions of radiocesium in tree stems were
      investigated to understand radiocesium transfer to trees at an early stage of
      massive contamination from the Fukushima nuclear disaster. A conifer species
      (Japanese red pine) and a broad-leaved species (Japanese konara oak) were
      selected to determine whether the radiocesium contamination pattern differs
      between species. Stem disks were collected at several heights and separated into
      outer bark, inner bark, and wood. The radiocesium concentration was the highest
      in the outer bark, followed by that in the inner bark and wood. The vertical
      distribution of the radiocesium concentration at each stem part differed between
      the species. The difference between species in radiocesium concentration of the
      outer bark could be explained by presence or absence of leaves at the time of the
      disaster. However, the reasons for the differences between species in the
      radiocesium concentration of the inner bark and wood are unclear. The radial
      distribution in the wood of the studied species showed a common pattern across
      stem disk heights and species. However, the radiocesium concentration ratio
      between sapwood and inner bark was significantly different between species.
      Although the radial contamination pattern in the wood was similar in the studied
      species during the early stage of contamination, the radiocesium transport
      pathway and allocation would be different between the species, and the
      contamination pattern will likely be different between the species at later
      stages. Continued investigations are important for understanding the radiocesium
      cycle and the accumulation of radiocesium in the tree stems of each species. 

PMID- 24661965
TI  - Effect of Cydonia oblonga Mill. leaf extracts or captopril on blood pressure and
      related biomarkers in renal hypertensive rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cydonia oblonga Mill. (COM) is used in
      traditional Uyghur medicine to treat or prevent cardiovascular disease. In a
      previous study COM leaf extracts were found to be active in renal hypertensive
      rats (RHR). The present study tests the dose-dependence of the effect of ethanol
      leaf extracts on hypertension and on biomarkers associated with blood pressure
      control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12
      (A), endothelin (ET) and nitric oxide (NO), compared to captopril. METHODS: Two
      kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six
      groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg
      (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment
      and every 2 weeks. Blood and kidney samples were collected after the last
      treatment to measure AII, PRA, A, ET and NO. RESULTS: RHR had increased blood
      pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced
      blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf
      extracts significantly and dose-dependently reduced blood pressure, AII, A, RA
      and ET, whereas NO was increased. The highest dose of COM had the same effects as
      captopril. CONCLUSION: The effects of COM extracts on blood pressure and
      biomarkers were dose-dependent and at the highest dose similar to those of
      captopril. This suggests an action of COM on the renin-angiotensin system, which
      could explain its antihypertensive effect.

PMID- 24661966
TI  - Lignans from the stems of Clematis armandii ("Chuan-Mu-Tong") and their anti
      neuroinflammatory activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The dried stems of Clematis armandii (Caulis
      clematidis armandii), named "Chuan-Mu-Tong" in Chinese Pharmacopoeia, have been
      traditionally used as an herbal remedy mainly for inflammation-associated
      diseases. The Aim of the study is to identify the potential anti
      neuroinflammatory components from Clematis armandii. MATERIALS AND METHODS: The
      ethanol extract of "Chuan-Mu-Tong" was suspended in H2O and exhaustively
      extracted with CH2Cl2. The CH2Cl2 fraction was successively subjected to column
      chromatography (CC) over silica gel, Sephadex LH-20, and semi-preparative HPLC.
      The structures of the isolated compounds were identified by spectroscopic methods
      and by comparison with those reported in the literature. Their anti
      neuroinflammatory activities were evaluated by inhibitory effects on pro
      inflammatory mediators [e.g. nitric oxide (NO) and tumor necrosis factor-alpha
      (TNF-alpha)] in lipopolysaccharide (LPS)-activated BV-2 cells. RESULTS: One new
      and sixteen known lignans were isolated and characterized. The absolute
      configuration of the new lignan, (7R,8S)-9-acetyl-dehydrodiconiferyl alcohol (1),
      was elucidated by a combination of 1D/2D NMR techniques and the Electronic
      Circular Dichroism (ECD) spectroscopy based on the empirical helicity rules. The
      anti-neuroinflammatory bioassay showed that compounds 1, (7R,8S)
      dehydrodiconiferyl alcohol (2), erythro-guaiacylglycerol-beta-coniferyl ether
      (5), and threo-guaiacylglycerol-beta-coniferyl ether (6) displayed significant
      inhibitory effects on NO production. Among them, neolignans 1 and 2 exhibited
      more potent activities than the positive control (N(G)-monomethyl-L-arginine, L
      NMMA), with an IC50 value of 9.3 and 3.9 MUM, respectively. Moreover, both 1 and
      2 were also found to concentration-dependently suppress the TNF-alpha release in
      LPS-stimulated BV-2 cells. CONCLUSION: The results revealed that lignans are the
      major components of "Chuan-Mu-Tong", and their anti-neuroinflammatory activities
      strongly support the traditional application of this herb medicine on
      inflammation. Moreover, the dihydrobenzo[b]furan neolignans 1 and 2 as well as
      Caulis clematidis armandii could be further exploited as new therapeutic agents
      to treat inflammation-mediated neurodegenerative and aging-associated diseases.

PMID- 24661967
TI  - Antinociceptive effect of ethanol extract of leaves of Lannea coromandelica.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lannea coromandelica (Houtt.) Merr. is a plant
      locally called "Jiga", found all over Bangladesh. Leaf of the plant is
      traditionally used in the treatment of local swellings, pains of body, toothache
      etc. This study evaluated the antinociceptive effect of the ethanol extract of L.
      coromandelica leaves (EELC). MATERIALS AND METHODS: The antinociceptive activity
      of the extract (at the doses of 50, 100, and 200 mg/kg) was evaluated by using
      chemical- and heat-induced pain models such as acetic acid-induced writhing, hot
      plate, tail immersion, formalin, and glutamate test. To verify the possible
      involvement of opioid receptor in the central antinociceptive effect of EELC,
      naloxone was used to antagonize the effect. Besides, the involvements of ATP
      sensitive K(+) channel and cGMP pathway were also justified by using
      glibenclemide and methylene blue. RESULTS: EELC demonstrated significant dose
      dependent antinociceptive activity in the chemical- and heat-induced nociception
      in mice models (p<0.05). These findings imply the involvement of both peripheral
      and central antinociceptive mechanisms. The use of naloxone confirmed the
      association of opioid receptors in the central antinociceptive effect. EELC also
      showed the involvements of ATP-sensitive K(+) channel and cGMP pathway for
      antinociceptive activity. CONCLUSIONS: This study reported the antinociceptive
      activity of the leaf of L. coromandelica and rationalized the traditional use of
      the leaf in the treatment of different painful conditions.

PMID- 24661968
TI  - An integrated strategy based on UPLC-DAD-QTOF-MS for metabolism and
      pharmacokinetic studies of herbal medicines: Tibetan "Snow Lotus" herb (Saussurea
      laniceps), a case study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea laniceps Hand.-Mazz. (SL) has long been
      used under the herbal name Tibetan "Snow Lotus" for the treatment of rheumatoid
      arthritis, stomachache and dysmenorrhea in Tibetan folk medicine. Since herbal
      medicine (HM) is a synergistical system with multiple components, both of the
      metabolism and pharmacokinetic studies of HM are interdependent. This study aimed
      to develop an integrated strategy based on the UPLC-DAD-QTOF-MS technique for
      metabolism and pharmacokinetic studies of HM. MATERIAL AND METHODS: SL was used
      here as a test herb to verify the feasibility of the proposed strategy. SL was
      administered to rats, then, the blood plasma, urine and feces were analyzed to
      determine the metabolic profiles. Using our strategy, umbelliferone and
      scopoletin were evaluated to be the key bioactive components. Their
      pharmacokinetic parameters were measured and biotransformation pathways were
      elucidated. RESULTS: After oral administration of SL to rats, 17 components in
      blood, 10 components in urine and 2 components in feces were identified and
      characterized using our UPLC-DAD-QTOF-MS method. Umbelliferone, scopoletin and
      their metabolites were found to be the major components involved in the
      metabolism process. Literature reports also suggest that umbelliferone and
      scopoletin are responsible for the therapeutic effects of SL, thus these two
      components were selected as the active markers for pharmacokinetic study. In the
      test of validity, the established method presented good linearity with R(2)>0.99.
      The relative standard deviation value was below 13.9% for precision, and recovery
      studies for accuracy were found to be within the range 91.8-112.5%. CONCLUSION:
      The present strategy offers, simultaneously, precision in quantitative analysis
      (metabolism study) and accuracy in quantitative analysis (pharmacokinetic study)
      with greater efficiency and less costs, which is therefore reliably used for
      integrated metabolism and pharmacokinetic studies of HM.

PMID- 24661969
TI  - Pharmacokinetics of artemisinin delivered by oral consumption of Artemisia annua
      dried leaves in healthy vs. Plasmodium chabaudi-infected mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese have used Artemisia annua as a tea
      infusion to treat fever for >2000 years. The active component is artemisinin.
      Previously we showed that when compared to mice fed an equal amount of pure
      artemisinin, a single oral dose of dried leaves of Artemisia annua (pACT)
      delivered to Plasmodium chabaudi-infected mice reduced parasitemia at least
      fivefold. Dried leaves also delivered >40 times more artemisinin in the blood
      with no toxicity. The pharmacokinetics (PK) of artemisinin delivered from dried
      plant material has not been adequately studied. MATERIALS AND METHODS: Healthy
      and Plasmodium chabaudi-infected mice were oral gavaged with pACT to deliver a
      100 mg kg(-1) body weight dose of artemisinin. Concentrations of serum
      artemisinin and one of its liver metabolites, deoxyartemisinin, were measured
      over two hours by GCMS. RESULTS: The first order elimination rate constant for
      artemisinin in pACT-treated healthy mice was estimated to be 0.80 h(-1) with an
      elimination half-life (T1/2) of 51.6 min. The first order absorption rate
      constant was estimated at 1.39 h(-1). Cmax and Tmax were 4.33 mg L(-1) and 60
      min, respectively. The area under the curve (AUC) was 299.5 mg min L(-1). In
      contrast, the AUC for pACT-treated infected mice was significantly greater at
      435.6 mg min L(-1). Metabolism of artemisinin to deoxyartemisinin was suppressed
      in infected mice over the period of observation. Serum levels of artemisinin in
      the infected mice continued to rise over the 120 min of the study period, and as
      a result, the T1/2 was not determined; the Cmax and Tmax were estimated at >=6.64
      mgL(-1) and >=120 min, respectively. Groups of healthy mice were also fed either
      artemisinin or artemisinin mixed in mouse chow. When compared at 60 min,
      artemisinin was undetectable in the serum of mice fed 100 mg AN kg(-1) body
      weight. When plant material was present either as mouse chow or Artemisia annua
      pACT, artemisinin levels in the serum rose to 2.44 and 4.32 mg L(-1),
      respectively, indicating that the presence of the plant matrix, even that of
      mouse chow, had a positive impact on the appearance of artemisinin in the blood.
      CONCLUSIONS: These results showed that artemisinin and one of its drug
      metabolites were processed differently in healthy and infected mice. The results
      have implications for possible therapeutic use of pACT in treating malaria and
      other artemisinin-susceptible diseases.

PMID- 24661970
TI  - Herniated lumbar disk as the initial presentation of sarcoidosis.

PMID- 24661971
TI  - Pyrexia, massive hepatomegaly, and extreme hyperferritinemia.

PMID- 24661972
TI  - Chest pain and elevated troponins in a patient with prior coronary artery
      disease: a diagnostic dilemma.

PMID- 24661973
TI  - [Potentially inappropriate prescribing in patients over 65 years-old in a primary
      care health centre].
AB  - OBJECTIVE: To identify potentially inappropriate prescriptions (PPI) and
      prescribing omissions (OP) by means of the STOPP/START criteria, as well as
      associated factors in >=65year old patients in a Primary Care setting in Spain.
      STUDY DESIGN: A cross-sectional, descriptive study. SETTING: Centro de Salud
      Monovar, Primary Health Care. STUDY PERIOD: 6months. PATIENTS RANDOM SAMPLE:
      247patients. ELIGIBILITY CRITERIA: >=65years patients who attended an urban
      Primary Care clinic 2 or more times were studied. Terminally ill and nursing home
      residents were excluded. METHODS: Data were collected from electronic clinical
      records. STOPP and START criteria were evaluated in each clinical record,
      including age, sex, co-morbidity, number of chronic prescriptions. MAIN OUTCOMES:
      PPI and OP identified by STOPP and START criteria, respectively. RESULTS: A total
      of 81 patients (32.8%) had PPI, with the most common being the long-term use of
      long-acting benzodiazepines in 17 (6.9%). OP was found in 73 (29.6%) patients,
      with the most common being the omission of statins in patients diagnosed with
      diabetes mellitus and/or one or more major cardiovascular risk factors in 21
      (8.5%). After adjustment by gender and age, correlations were found between PPI
      and multiple medication (OR: 2.02; 95%CI: 1.15-3.53; P=.014), and OP and
      polypharmacy (OR: 2.37; 95%CI: 1.32-4.24; P=0.004). CONCLUSIONS: Inappropriate
      prescribing in older people is frequent, and is mainly associated with long
      acting benzodiazepines. There are diabetic patients who do not have statins
      prescribed. Multiple medication is associated with PPI and OP.

PMID- 24661974
TI  - Regulation of LRP-1 expression: make the point.
AB  - The low-density lipoprotein receptor-related protein-1 (LRP-1) is a membrane
      receptor displaying both scavenging and signaling functions. The wide variety of
      extracellular ligands and of cytoplasmic scaffolding and signaling proteins
      interacting with LRP-1 gives it a major role not only in physiological processes,
      such as embryogenesis and development, but also in critical pathological
      situations, including cancer and neurological disorders. In this review, we
      describe the molecular mechanisms involved at distinct levels in the regulation
      of LRP-1, from its expression to the proper location and stability at the cell
      surface. 

PMID- 24661975
TI  - Use of mesenchymal stem cells for cutaneous repair and skin substitute
      elaboration.
AB  - Human mesenchymal stem cells (MSCs) are a heterogeneous population of fibroblast
      like cells, which are present in different locations, including bone marrow,
      adipose tissue, extra-foetal tissues, gingiva and dermis. MSCs, which present
      multipotency capacities, important expansive potential and immunotolerance
      properties, remain an attractive tool for tissue repair and regenerative
      medicine. Currently, several studies and clinical trials highlight the use of
      MSCs in cutaneous repair underlining that their effects are essentially due to
      the numerous factors that they release. MSCs are also used in skin substitute
      development. In this study, we will first discuss the different sources of MSCs
      actually available. We will then present results showing that bone marrow-derived
      MSCs prepared according to Good Manufacturing Practices and included in a dermal
      equivalent are able to promote appropriate epidermis growth and differentiation.
      These data demonstrate that bone marrow-derived MSCs represent a satisfactory
      alternative to dermal fibroblasts in order to develop skin substitute. In
      addition, MSCs could provide a useful alternative to sustain epidermis
      development and to promote wound healing. 

PMID- 24661976
TI  - Urinary peptidomics identifies potential biomarkers for major depressive
      disorder.
AB  - Major depressive disorder (MDD) is a debilitating psychiatric illness with no
      available objective laboratory-based diagnostic test. In this study, matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS)-based peptidomics was applied to identify potential urinary diagnostic
      biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients
      and 28 age- and gender-matched healthy controls (HC) was used to develop a
      peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was
      assessed in an independent blinded test set consisting of 24 MDD patients and 13
      age- and gender-matched HC. A combination of five potential biomarkers was
      identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test
      set. Moreover, the protein precursors of four of the five peptides were
      identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A
      I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core
      protein. Taken together, the peptide pattern may be valuable for establishing an
      objective laboratory-based diagnostic test for MDD. 

PMID- 24661977
TI  - Distinctiveness of prolonged grief disorder symptoms among survivors of the Great
      East Japan Earthquake and Tsunami.
AB  - Prolonged Grief Disorder (PGD) has been proposed for diagnostic classification as
      an independent psychiatric disorder. Previous research has investigated it in
      relation to other axis I disorders in order to determine whether it could be
      considered an independent nosological entity. The distinctiveness of this
      condition was apparent in cases of ordinary bereavement and in those following
      human-made disasters. However, this disorder may be expanded to include
      bereavement resulting from natural disasters. The present study aims to explore
      the differences between this disorder and posttraumatic stress disorder or major
      depressive disorder as experienced after the Great East Japan Earthquake and
      Tsunami. The subjects were 82 hospital workers. Each type of disorder was
      assessed by means of the Inventory of Complicated Grief, the Impact of Event
      Scale-Revised, and the Center for Epidemiological Studies Depression Scale.
      Exploratory factor analysis showed 3 dimensions, with PGD items independently
      clustering in the same dimension. Our findings support the uniqueness of PGD even
      in a post-natural disaster situation in a non-Western culture and warrant grief
      intervention for high-risk bereaved survivors. 

PMID- 24661978
TI  - Bovine Papillomavirus: New Insights into an Old Disease.
AB  - Bovine papillomaviruses (BPVs) are small DNA tumoral viruses able to induce
      benign cutaneous and/or mucosal epithelial lesions. Generally, the benign tumours
      affecting the skin or mucosa spontaneously regress, but under special
      circumstances, the defence system may be overwhelmed, thus leading to cancer,
      especially in the presence of immunosuppressant and mutagen agents from bracken
      fern. To date, thirteen different BPV genotypes have been associated with skin
      and mucosal tumours in cattle, and out of these, only four types (BPV-1, -2, -5
      and -13) cross-infect other species. Recent investigations in vivo have revealed
      new insights into the epidemiology and pathogenesis of this viral infection. This
      review briefly discusses viral epidemiology, will give data on BPV genome
      structure and viral genes and will describe the cellular events and new aspects
      of both cutaneous and mucosal tumours in large ruminants. Finally, some aspects
      of active immunization will be described. 

PMID- 24661979
TI  - Combination of LC-MS/MS aldosterone and automated direct renin in screening for
      primary aldosteronism.
AB  - BACKGROUND: Aldosterone to renin ratio (ARR) is used in screening for primary
      aldosteronism (PA). However, there are only few studies on the influence of assay
      methods on ARR and its cut-off limits. METHODS: Plasma direct renin
      immunoreactivity by chemiluminescence immunoassay (DR) was compared to renin
      activity assay (PRA), and a specific liquid chromatography-mass spectrometric
      method (LC-MS/MS) to radioimmunoassay (RIA) for plasma aldosterone. There were 75
      samples for renin assays, and 42 samples of 39 patients for both renin and
      aldosterone assays. PA screening was considered positive if ARR by the
      aldosterone RIA:PRA was >=800pmol/L:MUg/L/h or by LC-MS/MS:DR>=44pmol/L:ng/L.
      RESULTS: The correlation between the DR and PRA methods (n=75, r(2)=0.845) and
      between LC-MS/MS and RIA (n=42, r(2)=0.973) was high in general, but low between
      the renin methods (n=49, r(2)=0.435) at low PRA values. When ARR was used in
      screening for PA, there were three divergent cases (positive only by alternative
      methods), but when applied in combination with criteria for elevated aldosterone,
      the methods showed good agreement, resulting in eight positive and 31 negative
      screening results. CONCLUSIONS: The automated DR assay combined with LC-MS/MS
      method for aldosterone provides a rapid, reliable, and specific method for
      screening of PA.

PMID- 24661980
TI  - The development and validation of a method using high-resolution mass
      spectrometry (HRMS) for the qualitative detection of antiretroviral agents in
      human blood.
AB  - BACKGROUND: Antiretroviral drugs are used for the treatment and prevention of HIV
      infection. Non-adherence to antiretroviral drug regimens can compromise their
      clinical efficacy and lead to emergence of drug-resistant HIV. Clinical trials
      evaluating antiretroviral regimens for HIV treatment and prevention can also be
      compromised by poor adherence and non-disclosed off-study antiretroviral drug
      use. This report describes the development and validation of a high throughput,
      qualitative method for the identification of antiretroviral drugs using high
      resolution mass spectrometry (HRMS) for the retrospective assessment of off-study
      antiretroviral drug use and the determination of potential antiretroviral therapy
      (ART) non-compliance. METHODS: Serum standards were prepared that contained 15
      antiretroviral drugs: 9 protease inhibitors (PIs), 4 nucleotide/nucleoside
      reverse transcriptase inhibitors (NRTIs), and 2 non-nucleoside/nucleotide reverse
      transcriptase inhibitors (NNRTIs). Analytical separation was achieved on a
      Hypersil Gold PFP (100*3mm) column and the eluent was analyzed using the Thermo
      Exactive Orbitrap mass spectrometer (Exactive-MS) operated in full scan mode.
      Limit of identification, signal intensity precision, retention time analysis,
      selectivity, and carryover studies were conducted. Concordance with liquid
      chromatographic-tandem mass spectrometric (LC-MS/MS) methods was evaluated using
      remnant plasma samples from a clinical trial. RESULTS: The limit of
      identification ranged from 5 to 10ng/ml for 14 drugs (9 PIs, 1 NNRTI, 4 NRTIs)
      and was 150ng/ml for 1 NNRTI. Precision studies with high and low control
      mixtures revealed signal intensity coefficients of variation of 3.0-27.5%. The
      Exactive-MS method was selective for the compounds of interest. Overall,
      concordance ranged from 89.1% to 100% for the screening of antiretroviral drugs
      in clinical plasma specimens as compared to LC-MS/MS methods. CONCLUSION: Using
      the Exactive-MS, we developed and validated a highly selective, robust method for
      the multiplexed detection of 15 antiretroviral drugs.

PMID- 24661981
TI  - Technology use among adults who are deaf and hard of hearing: a national survey.
AB  - As society becomes increasingly more dependent on technology, information
      regarding the use, preference, and accessibility of commonly used devices and
      services among individuals who are deaf and hard of hearing (DHH) is crucial.
      Developing technologies that are functional and appropriately accessible allows
      persons who are DHH to fully participate in society, education, and business
      while also providing opportunities for personal and professional advancement.
      Although a few international studies have addressed the technology use of
      individuals who are DHH, none exist that focus on the needs, preferences, and
      accessibility of current Internet- and mobile-based technologies. Consequently, a
      national survey was conducted in the United States to determine the preference,
      frequency of use, and accessibility of various technologies (hardware, software,
      Web sites) by adults who are DHH and living in the United States. Findings
      indicate frequent use of smartphones and personal computers, specifically for
      text-based communication and web surfing, and little use of
      Teletypewriter/Telecommunications Device for the Deaf. Web site feature
      preferences include pictures and text, and captions over signed translations.
      Some results varied by demographics. 

PMID- 24661982
TI  - Modulation of behavior by the histaminergic system: lessons from H(1)R-and H(2)R
      deficient mice.
AB  - Besides acting in the immune system, histamine is also a neurotransmitter in the
      central nervous system. The H1R causes central side effects, e.g. of first
      generation antihistamines, antidepressants or antipsychotics and represents the
      component of the central histaminergic system most extensively studied in
      behavior experiments with knock-out mice. Central effects of H2R are similar, but
      only few behavioral results from knockout models are available. We summarize the
      behavior phenotype of H1R- and H2R-deficient mice, revealing histaminergic
      modulation of behaviors like locomotor activity, cognition, emotional states,
      arousal, sleep and wakefulness, circadian rhythm, pain perception, food intake
      and energy consumption, respiration and susceptibility to seizures. Knock-out
      models demonstrate several central effects of H1R and H2R that are not clinically
      and therapeutically exploited to date. We critically discuss problems and
      pitfalls of both the knock-out mouse technique and the pharmacological approach
      with receptor-selective ligands. The behavioral characterization of Hrh1(-/-)-
      and Hrh2(-/-)-mice is crucial, because many pharmacological agents lack the
      required selectivity to unequivocally address the functions of a single histamine
      receptor subtype. 

PMID- 24661983
TI  - Perspectives and possible applications of the rubber hand and virtual hand
      illusion in non-invasive rehabilitation: technological improvements and their
      consequences.
AB  - This review introduces theoretical aspects of the rubber hand illusion (RHI) and
      virtual hand illusion (VHI), and discusses their possible clinical applications.
      It also presents technical improvements regarding the realization of the RHI and
      VHI and their relation to rehabilitation issues. There is presently little
      evidence describing the value of the RHI and VHI as indices in the diagnosis or
      treatment of different pathologies, likely because of a lack of standardization
      in reporting the results of RHI and VHI studies. In contrast, a new emerging "out
      of-body illusion" appears to be an interesting new approach; however, as in RHI
      and VHI, there are additional consequences regarding its application in clinical
      settings because of its technological demands. This review considers the
      acceptance of technology and the realization of immersion/presence in the context
      of virtual rehabilitation. 

PMID- 24661984
TI  - Drosophila models of early onset cognitive disorders and their clinical
      applications.
AB  - The number of genes known to cause human monogenic diseases is increasing
      rapidly. For the extremely large, genetically and phenotypically heterogeneous
      group of intellectual disability (ID) disorders, more than 600 causative genes
      have been identified to date. However, knowledge about the molecular mechanisms
      and networks disrupted by these genetic aberrations is lagging behind. The fruit
      fly Drosophila has emerged as a powerful model organism to close this knowledge
      gap. This review summarizes recent achievements that have been made in this model
      and envisions its future contribution to our understanding of ID genetics and
      neuropathology. The available resources and efficiency of Drosophila place it in
      a position to tackle the main challenges in the field: mapping functional modules
      of ID genes to provide conceptually novel insights into the genetic control of
      cognition, tailored functional studies to improve 'next-generation' diagnostics,
      and identification of reversible ID phenotypes and medication. Drosophila's
      behavioral repertoire and powerful genetics also open up perspectives for
      modeling genetically complex forms of ID and neuropsychiatric disorders, which
      overlap in their genetic etiologies. In conclusion, Drosophila provides many
      opportunities to advance future medical genomics of early onset cognitive
      disorders. 

PMID- 24661985
TI  - Representation in development: from a model system to some general processes.
AB  - The view that filial imprinting might serve as a useful model system for studying
      the neurobiological basis of memory was inspired, at least in part, by a simple
      idea: acquired filial preferences reflect the formation of a memory or
      representation of the imprinting object itself, as opposed to the change in the
      efficacy of stimulus-response pathways, for example. We provide a synthesis of
      the evidence that supports this idea; and show that the processes of memory
      formation observed in filial imprinting find surprisingly close counterparts in
      other species, including our own. 

PMID- 24661987
TI  - Interactions between brain structure and behavior: the corpus callosum and
      bimanual coordination.
AB  - Bimanual coordination skills are required for countless everyday activities, such
      as typing, preparing food, and driving. The corpus callosum (CC) is the major
      collection of white matter bundles connecting both hemispheres that enables the
      coordination between the two sides of the body. Principal evidence for this brain
      behavior relationship in humans was first provided by research on callosotomy
      patients, showing that sectioning (parts of) the CC affected interactions between
      both hands directly. Later, new noninvasive in vivo imaging techniques, such as
      diffusion tensor imaging, have energized the study of the link between
      microstructural properties of the CC and bimanual performance in normal
      volunteers. Here we discuss the principal factors (such as age, pathology and
      training) that mediate the relationship between specific bimanual functions and
      distinct anatomical CC subdivisions. More specifically, the question is whether
      different bimanual task characteristics can be mapped onto functionally distinct
      CC subregions. We review the current status of this mapping endeavor, and propose
      future perspectives to inspire research on this unique link between brain
      structure and behavior. 

PMID- 24661988
TI  - Difficult removal of fully covered self expandable metal stents (SEMS) for benign
      biliary strictures: the "SEMS in SEMS" technique.
AB  - BACKGROUND: Removal of biliary Fully Covered Self Expandable Metal Stents can
      fail due to stent migration and/or hyperplastic ingrowth/overgrowth. METHODS: A
      case series of 5 patients with benign biliary strictures (2 post-cholecystectomy,
      2 following liver transplantation and 1 related to chronic pancreatitis) is
      reported. The biliary stricture was treated by temporary insertion of Fully
      Covered Self Expandable Metal Stents. Stent removal failed due to proximal stent
      migration and/or overgrowth. Metal stent removal was attempted a few weeks after
      the insertion of another Fully Covered Metal Stent into the first one. RESULTS:
      The inner Fully Covered Self Expandable Metal Stent compressed the hyperplastic
      tissue, leading to the extraction of both the stents in all cases. Two
      complications were reported as a result of the attempt to stents removal (mild
      pancreatitis and self-limited haemobilia). CONCLUSION: In the present series, the
      "SEMS in SEMS" technique revealed to be effective when difficulties are
      encountered during Fully Covered Self Expandable Metal Stents removal.

PMID- 24661989
TI  - Cholesterol change in coeliac patients following gluten-free diet depends on
      baseline levels.

PMID- 24661990
TI  - Are the antiplatelet and profibrinolytic properties of selective serotonin
      reuptake inhibitors relevant to their brain effects?
AB  - The serotonin transporter (SERT) is found in neuron and platelet membranes.
      Selective serotonin-reuptake inhibitors (SSRIs) are widely prescribed for severe
      depression. They may at least partly counteract the effects of serotonin on the
      vascular biology system, can lower agonists-induced platelet activation,
      aggregation and procoagulant activity in vitro, thus modulating platelet
      thrombogenicity. Other effects, such as those mediated through PAI-1 modulation,
      may indirectly influence neurobiology-relevant mechanisms involved in depression.
      Patients receiving SSRIs are at increased bleeding risk and decreased risk of
      arterial occlusive events, such as myocardial infarction, compared to those using
      non-SSRI antidepressants. The objectives of this review were to highlight
      antiplatelet and profibrinolytic properties of SSRIs and discuss the potential
      role of these activities in the context of SSRI brain effects. 

PMID- 24661991
TI  - Fungal nail infection: diagnosis and management.

PMID- 24661986
TI  - The Deakin/Graeff hypothesis: focus on serotonergic inhibition of panic.
AB  - The Deakin/Graeff hypothesis proposes that different subpopulations of
      serotonergic neurons through topographically organized projections to forebrain
      and brainstem structures modulate the response to acute and chronic stressors,
      and that dysfunction of these neurons increases vulnerability to affective and
      anxiety disorders, including panic disorder. We outline evidence supporting the
      existence of a serotonergic system originally discussed by Deakin/Graeff that is
      implicated in the inhibition of panic-like behavioral and physiological
      responses. Evidence supporting this panic inhibition system comes from the
      following observations: (1) serotonergic neurons located in the 'ventrolateral
      dorsal raphe nucleus' (DRVL) as well as the ventrolateral periaqueductal gray
      (VLPAG) inhibit dorsal periaqueductal gray-elicited panic-like responses; (2)
      chronic, but not acute, antidepressant treatment potentiates serotonin's
      panicolytic effect; (3) contextual fear activates a central nucleus of the
      amygdala-DRVL/VLPAG circuit implicated in mediating freezing and inhibiting panic
      like escape behaviors; (4) DRVL/VLPAG serotonergic neurons are central
      chemoreceptors and modulate the behavioral and cardiorespiratory response to
      panicogenic agents such as sodium lactate and CO2. Implications of the panic
      inhibition system are discussed. 

PMID- 24661992
TI  - Comparison of clenbuterol and salbutamol accumulation in the liver of two
      different mouse strains.
AB  - In the European Union, beta(2)-adrenergic agonists like clenbuterol and
      salbutamol are banned from use as growth promoters. Although clenbuterol and
      salbutamol both accumulate in the liver, differences in the accumulation rate can
      be seen among animal species due to different beta(2)-adrenoreceptor
      distributions. The aim of this study was to compare the accumulation of the two
      in the liver tissue of two different mouse strains. The study included 200 8-week
      old BALB/c and C57/BL/6 mice. One group of BALB/c (40) and one group of C57/BL/6
      (40) mice were treated with 2.5 mg/kg body mass clenbuterol per os for 28 days.
      The remaining two animal groups were treated with salbutamol in the same manner.
      The animals were then randomly sacrificed on day 1, 15 and 30 post treatments.
      Despite of the same treatment dose, the results revealed clenbuterol to persist
      in the liver tissue longer than salbutamol. On post treatment day 30, the
      concentration of clenbuterol residue in C57/BL/6 and BALB/c mice liver tissue
      were 0.23 +/- 0.02 and 0.21 +/- 0.03 ng/g, respectively, while residues of
      salbutamol were not detected. When comparing the accumulation of both compounds
      between the two mouse strains, it becomes apparent that no significant difference
      (P > 0.05) in the accumulation rate can be found.

PMID- 24661993
TI  - Amphipathic short helix-stabilized peptides with cell-membrane penetrating
      ability.
AB  - We synthesized four types of arginine-based amphipathic nonapeptides, including
      two homochiral peptides, R-(L-Arg-L-Arg-Aib)3-NH2 (R=6-FAM-beta-Ala: FAM-1; R=Ac:
      Ac-1) and R-(D-Arg-D-Arg-Aib)3-NH2 (R=6-FAM-beta-Ala: ent-FAM-1; R=Ac: ent-Ac-1);
      a heterochiral peptide, R-(L-Arg-D-Arg-Aib)3-NH2 (R=6-FAM-beta-Ala: FAM-2; R=Ac:
      Ac-2); and a racemic mixture of diastereomeric peptides, R-(rac-Arg-rac-Arg-Aib)3
      NH2 (R=6-FAM-beta-Ala: FAM-3; R=Ac: Ac-3), and then investigated the relationship
      between their secondary structures and their ability to pass through cell
      membranes. Peptides 1 and ent-1 formed stable one-handed alpha-helical structures
      and were more effective at penetrating HeLa cells than the non-helical peptides 2
      and 3.

PMID- 24661994
TI  - [Nosocomial infections in intensive care units].
AB  - Nosocomial infections (NI) still have a high incidence in intensive care units
      (ICUs), and are becoming one of the most important problems in these units. It is
      well known that these infections are a major cause of morbidity and mortality in
      critically ill patients, and are associated with increases in the length of stay
      and excessive hospital costs. Based on the data from the ENVIN-UCI study, the
      rates and aetiology of the main nosocomial infections have been described, and
      include ventilator-associated pneumonia, urinary tract infection, and both
      primary and catheter related bloodstream infections, as well as the incidence of
      multidrug-resistant bacteria. A literature review on the impact of different
      nosocomial infections in critically ill patients is also presented. Infection
      control programs such as zero bacteraemia and pneumonia have been also analysed,
      and show a significant decrease in NI rates in ICUs.

PMID- 24661995
TI  - [Preventive measures for avoiding transmission of microorganisms between
      hospitalised patients. Hand hygiene].
AB  - Health-care associated infections are an important public health problem
      worldwide. The rates of health-care associated infections are indicators of the
      quality of health care. The infection control activities related to prevention of
      transmission of hospital microorganisms can be grouped in 4 mayor areas: standard
      precautions, specific precautions (including isolation if appropriate),
      environmental cleaning and disinfection, and surveillance activities (including
      providing infection rates and monitoring procedures). Hand hygiene and the
      correct use of gloves are the most important measures to prevent health-care
      associated infections and to avoid the dissemination of multidrug-resistant
      microorganisms. Continuous educational activities aimed at improving adherence to
      hand hygiene are needed. Periodical assessment of adherence to hand hygiene
      recommendations with feed-back have been shown to provide sustained improvement.
      Several complementary activities are being evaluated, including skin
      decolonization prior to certain surgeries, a package of measures in patients with
      central venous catheters or mechanical ventilation, and universal body hygiene
      with chlorhexidine. The present area of discussion concerns in which situations
      and in which groups would such measures be effective and efficient. 

PMID- 24661996
TI  - [Aortic abdominal aneurysm infection due to Eikenella corrodens].

PMID- 24661997
TI  - Mitochondria: are mitochondria accessory to metastasis?
AB  - Since the nineteenth century the importance of mitochondria in cellular
      physiology has been growing steadily. Not only the organelle harbors the main
      systems for ATP generation, but also buffers the redox potential in the cytosol
      and is one of the protagonists of the intrinsic pathway for apoptosis. In tumor
      cells, mitochondria went from being dysfunctional compartments to playing a
      supportive or perhaps even a triggering part in metastasis. This "Organelle In
      Focus" article discusses the classical metabolic events that occur in
      mitochondria and why these pathways could be essential for the onset of the
      malignant phenotype. Finally, we propose that the oxidative metabolism of tumor
      cells in conjunction with the inactivation of anoikis may have been coopted
      through a non-adaptive evolutionary process. 

PMID- 24661998
TI  - Blocking interaction of viral gp120 and CD4-expressing T cells by single-stranded
      DNA aptamers.
AB  - To investigate the potential clinical application of aptamers to prevention of
      HIV infection, single-stranded DNA (ssDNA) aptamers specific for CD4 were
      developed using the systematic evolution of ligands by exponential enrichment
      approach and next generation sequencing. In contrast to RNA-based aptamers, the
      developed ssDNA aptamers were stable in human serum up to 12h. Cell binding
      assays revealed that the aptamers specifically targeted CD4-expressing cells with
      high binding affinity (Kd=1.59nM), a concentration within the range required for
      therapeutic application. Importantly, the aptamers selectively bound CD4 on human
      cells and disrupted the interaction of viral gp120 to CD4 receptors, which is a
      prerequisite step of HIV-1 infection. Functional studies showed that the aptamer
      polymers significantly blocked binding of viral gp120 to CD4-expressing cells by
      up to 70% inhibition. These findings provide a new approach to prevent HIV-1
      transmission using oligonucleotide aptamers. 

PMID- 24661999
TI  - Atrazine contamination at the watershed scale and environmental factors affecting
      sampling rates of the polar organic chemical integrative sampler (POCIS).
AB  - Polar organic chemical integrative samplers (POCIS) were used to estimate
      atrazine contamination at 24 stream/river sites located across a watershed with
      land use ranging from 6.7 to 97.4% annual crops and surface water nitrate
      concentrations ranging from 3 to 5404 MUg/L. A gradient of atrazine contamination
      spanning two orders of magnitude was observed over two POCIS deployments of 28 d
      and was positively correlated with measures of agricultural intensity. The
      metabolite desisopropyl atrazine was used as a performance reference compound in
      field calibration studies. Sampling rates were similar between field sites but
      differed seasonally. Temperature had a significant effect on sampling rates while
      other environmental variables, including water velocity, appeared to have no
      effect on sampling rates. A performance reference compound approach showed
      potential in evaluating spatial and temporal differences in field sampling rates
      and as a tool for further understanding processes governing uptake of polar
      compounds by POCIS. 

PMID- 24662000
TI  - Bacterial metal resistance genes and metal bioavailability in contaminated
      sediments.
AB  - In bacteria a metal may be defined as bioavailable if it crosses the cytoplasmic
      membrane to reach the cytoplasm. Once inside the cell, specific metal resistance
      systems may be triggered. In this research, specific metal resistance genes were
      used to estimate metal bioavailability in sediment microbial communities. Gene
      levels were measured by quantitative PCR and correlated to metals in sediments
      using five different protocols to estimate dissolved, particle-adsorbed and
      occluded metals. The best correlations were obtained with czcA (a Cd/Zn/Co efflux
      pump) and Cd/Zn adsorbed or occluded in particles. Only adsorbed Co was
      correlated to czcA levels. We concluded that the measurement of czcA gene levels
      by quantitative PCR is a promising tool which may complement the classical
      approaches used to estimate Cd/Zn/Co bioavailability in sediment compartments. 

PMID- 24662001
TI  - Combining measurements and modelling to quantify the contribution of atmospheric
      fallout, local industry and road traffic to PAH stocks in contrasting catchments.
AB  - Various sources supply PAHs that accumulate in soils. The methodology we
      developed provided an evaluation of the contribution of local sources (road
      traffic, local industries) versus remote sources (long range atmospheric
      transport, fallout and gaseous exchanges) to PAH stocks in two contrasting
      subcatchments (46-614 km2) of the Seine River basin (France). Soil samples (n =
      336) were analysed to investigate the spatial pattern of soil contamination
      across the catchments and an original combination with radionuclide measurements
      provided new insights into the evolution of the contamination with depth.
      Relationships between PAH concentrations and the distance to the potential
      sources were modelled. Despite both subcatchments are mainly rural, roadside
      areas appeared to concentrate 20% of the contamination inside the catchment while
      a local industry was found to be responsible for up to 30% of the stocks. Those
      results have important implications for understanding and controlling PAH
      contamination in rural areas of early-industrialized regions.

PMID- 24662002
TI  - High tolerance of subalpine grassland to long-term ozone exposure is independent
      of N input and climatic drivers.
AB  - In a seven-year study, we tested effects of increased N and O3 deposition and
      climatic conditions on biomass of subalpine grassland. Ozone risk was assessed as
      exposure (AOT40) and as stomatal flux (POD0,1). We hypothesized that productivity
      is higher under N- and lower under O3 deposition, with interactions with climatic
      conditions. Aboveground biomass was best correlated with growing-degree days for
      May (GDDMay). Nitrogen deposition increased biomass up to 60% in the highest
      treatment, and 30% in the lowest addition. Also belowground biomass showed a
      positive N-response. Ozone enrichment had no effect on biomass, and no
      interaction between O3 and N was observed. Growth response to N deposition was
      not correlated to GDDMay or precipitation, but indicated a cumulative effect over
      time. Productivity of subalpine grassland is tolerant to increasing ozone
      exposure, independent of N input and climatic drivers. N deposition rates at
      current critical loads, strongly increase the grassland yield. 

PMID- 24662003
TI  - Clinical manifestations and outcomes of the treatment of patients with GABAB
      encephalitis.
AB  - Encephalitis associated with anti-gamma-aminobutyric acid-B (GABAB) receptor
      antibodies has been identified recently. However, only a few cases have been
      reported to date and its clinical manifestations and prognosis have not been
      investigated systematically. We identified five cases of GABAB encephalitis in
      Korea. Here we present the clinical features, treatment responses, and brain
      positron emission tomography findings of the cases. The patients had a clinical
      triad of memory changes, seizure, and association with small-cell lung cancer.
      Early diagnosis and comprehensive immune modulation may provide a good outcome.

PMID- 24662004
TI  - New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and
      multiple sclerosis relapse. Changes after glucocorticoids.
AB  - In multiple sclerosis (MS), the immune damage to the central nervous system
      results from the net balance between self-reactive and immunoregulatory cells,
      among other factors. We identified novel perforin-expressing regulatory B-cells
      (BReg) in patients with clinically isolated syndrome, significantly enriched
      within the cerebrospinal fluid when compared to peripheral blood, of memory B
      cell phenotype (CD19(+)CD25(+), CD19(+)CD25(+)FoxP3(+) and CD19(+)FoxP3(+),
      p=0.007, p=0.06 and p=0.03, respectively). These BReg subsets were also higher in
      relapsing-remitting MS during relapse symptoms than in non-clinically active MS
      patients. Suppressive effects by CD19(+)CD25(+hi) BReg on CD4(+) T cell
      proliferation seem to be mediated at least in part by perforin/granzyme pathway.
      To our knowledge, this is the first report that shows cytolytic perforin/granzyme
      granule storage in B cells; the interesting point is its involvement on BReg cell
      immunosuppressive mechanisms, similarly to that in TReg cells. Our data may
      extend the understanding of pathophysiological processes in MS immunoregulation.

PMID- 24662005
TI  - Immunoglobulin GM and FcgammaRIIIa genotypes influence cytotoxicity of
      neuroblastoma cells.
AB  - Immunoglobulin GM (gamma marker) allotypes are strongly associated with
      neuroblastoma, but the mechanism is not known. One mechanism could involve
      antibody-dependent cell-mediated cytotoxicity (ADCC) of neuroblastoma cells.
      Using an ADCC inhibition assay, we show that IgG1 expressing GM 3+,1-,2-
      allotypes blocked all phenylalanine-expressing FcgammaRIIIa present on NK cells,
      resulting in total inhibition of anti-GD2 antibody-mediated ADCC of GD2
      overexpressing neuroblastoma cells. In contrast, the inhibitory effect of this
      protein was significantly lower when the NK cells were homozygous for the valine
      allele of FcgammaRIIIa (100 vs. 21%; p=0.00004). These and other findings
      presented here could lead to a more effective immunotherapy of neuroblastoma.

PMID- 24662006
TI  - Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autism spectrum
      disorders.
AB  - The IGF-I/PI3K/AKT/mTOR signaling pathway plays an important role in the
      regulation of cell growth, proliferation, differentiation, motility, survival,
      metabolism and protein synthesis. Insulin-like growth factor-I (IGF-I) is
      synthesized in the liver and fibroblasts, and its biological actions are mediated
      by the IGF-I receptor (IGF-IR). The binding of IGF-I to IGF-IR leads to the
      activation of phosphatidylinositol 3-kinase (PI3K). Activated PI3K stimulates the
      production of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] and
      phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3]. The PH domain of AKT
      (protein kinase B, PKB) (v-AKT murine thymoma viral oncogene homolog) binds to
      PI(4,5)P2 and PI(3,4,5)P3, followed by phosphorylation of the Thr308 and Ser473
      regulatory sites. Tuberous sclerosis complex 1 (TSC1) and TSC2 are upstream
      regulators of mammalian target of rapamycin (mTOR) and downstream effectors of
      the PI3K/AKT signaling pathway. The activation of AKT suppresses the TSC1/TSC2
      heterodimer, which is an upstream regulator of mTOR. Dysregulated IGF
      I/PI3K/AKT/mTOR signaling has been shown to be associated with autism spectrum
      disorders (ASDs). In this review, we discuss the emerging evidence for a
      functional relationship between the IGF-I/PI3K/AKT/mTOR pathway and ASDs, as well
      as a possible role of this signaling pathway in the diagnosis and treatment of
      ASDs. 

PMID- 24662007
TI  - Pre-pubertal serum leptin levels and sensitivity to central leptin injection of
      prenatally undernourished female rats.
AB  - It has been reported that intrauterine undernutrition is closely associated with
      the pathogeneses of certain diseases in adulthood; i.e., insulin resistance and
      diabetes, and that leptin resistance plays a pivotal role in the pathology of
      such intrauterine growth restriction (IUGR)-related conditions. Therefore,
      examinations of IUGR-induced leptin resistance in early developmental period are
      important for protecting against future disease. In this study, the effects of
      prenatal undernutrition on the serum leptin levels and central leptin responses
      of rats during the neonatal and/or pre-pubertal period were examined. The 50%
      food-restricted undernourished dams' offspring (UNO) exhibited a significantly
      lower birth weight than the normal nutrition dams' offspring (NNO). However, the
      UNO grew rapidly, and their mean body weight had caught up with that of the NNO
      by postnatal day 8. Thus, there were no significant differences between the body
      weights of the two groups at postnatal day 12, 16, 20, or 28. The serum leptin
      levels of the UNO were significantly higher than those of the NNO at postnatal
      days 20 and 28. At postnatal day 28, no significant difference in the
      hypothalamic mRNA level of neuropeptide Y, which is the main target of leptin, or
      that of ObRb, which is the leptin receptor, was detected between the NNO and UNO.
      The chronic intracerebroventricular injection of leptin attenuated body weight
      gain in both the NNO and UNO; however, there were no significant differences
      between the body weights of the two groups at any of the examined postnatal time
      points, indicating that the UNO and NNO exhibited similar central sensitivity to
      leptin during the pre-pubertal period. These results suggest that prenatal
      undernutrition induces leptin resistance until the neonatal to pre-pubertal
      period and that these alterations might be caused by impaired transportation of
      leptin to central tissues. 

PMID- 24662008
TI  - The renal channelopathies.
AB  - Specific channels permit movement of selected ions through cellular membranes,
      and are of vital importance in a number of physiological processes, particularly
      in excitable tissues such as nerve and muscle, but also in endocrine organs and
      in epithelial biology. Disorders of channel proteins are termed channelopathies,
      and their importance is increasingly recognised within medicine. In the kidney,
      ion channels have critical roles enabling sodium and potassium reuptake or
      excretion along the nephron, in magnesium homeostasis, in the control of water
      reabsorption in the collecting duct, and in determining glomerular permeability.
      In this review, we assess the channelopathies encountered in each nephron
      segment, and see how their molecular and genetic characterisation in the past 20
      30 years has furthered our understanding of normal kidney physiology and disease
      processes, aids correct diagnosis and promises future therapeutic opportunities. 

PMID- 24662009
TI  - Effect of whole-body periodic acceleration on exercise-induced muscle damage
      after eccentric exercise.
AB  - PURPOSE: To examine the effects of whole-body periodic acceleration (pGz) on
      exercise-induced-muscle-damage (EIMD) -related symptoms induced by unaccustomed
      eccentric arm exercise. METHODS: Seventeen active young men (23.4 +/- 4.6 y) made
      6 visits to the research facility over a 2-wk period. On day 1, subjects
      performed a 1-repetition-maximum (1RM) elbow-flexion test and were randomly
      assigned to the pGz (n = 8) or control group (n = 9). Criterion measurements were
      taken on day 2, before and immediately after performance of the eccentric
      exercise protocol (10 sets, 10 repetitions using 120% 1RM) and after the recovery
      period. During subsequent sessions (24, 48, 72, and 96 h) these data were
      collected before pGz or passive recovery. Measurements included isometric
      strength (maximal voluntary contraction [MVC]), blood markers (creatine kinase,
      myoglobin, IL-6, TNF-alpha, TBARS, PGF2alpha, protein carbonyls, uric acid, and
      nitrites), soreness, pain, circumference, and range of motion (ROM). RESULTS:
      Significantly higher MVC values were seen for pGz throughout the recovery period.
      Within-group differences were seen in myoglobin, IL-6, IL-10, protein carbonyls,
      soreness, pain, circumference, and ROM showing small negative responses and rapid
      recovery for the pGz condition. CONCLUSION: Our results demonstrate that pGz can
      be an effective tool for the reduction of EIMD and may contribute to the training
      adaptation cycle by speeding up the recovery of the body due to its performance
      loss-lessening effect.

PMID- 24662010
TI  - Perspectives on neuroinflammation and excitotoxicity: a neurotoxic conspiracy?
AB  - Emerging evidences underline the ability of several environmental contaminants to
      induce an inflammatory response within the central nervous system, named
      neuroinflammation. This can occur as a consequence of a direct action of the
      neurotoxicant to the CNS and/or as a response secondary to the activation of the
      peripheral inflammatory response. In both cases, neuroinflammation is driven by
      the release of several soluble factors among which pro-inflammatory cytokines. IL
      1beta and TNF-alpha have been extensively studied for their effects within the
      CNS and emerged for their role in the modulation of the neuronal response, which
      allow the immune response to integrate with specific neuronal functions, as
      neurotransmission and synaptic plasticity. In particular, it has been evidenced a
      potential detrimental link between these cytokines and the glutamatergic system
      that seems to be part of increased brain excitability and excitotoxicity
      occurring in different pathological conditions. Aim of this mini-review will be
      to present experimental evidence on the way IL-1beta and TNF-alpha impact
      neurons, focusing on the glutamatergic signalling, to provide a perspective on
      novel pathways possibly involved in environmental contaminants neurotoxicity. 

PMID- 24662011
TI  - [The involvement of vulnerable people in participatory research in primary care:
      a literature review].

PMID- 24662012
TI  - [Understanding the adaptation of the Hospital of Logo, Democratic Republic of
      Congo, to an exogenous health program].

PMID- 24662013
TI  - Assessment with unenhanced MRI techniques of renal morphology and hemodynamic
      changes during acute kidney injury and chronic kidney disease in mice.
AB  - BACKGROUND/AIMS: Changes in renal oxygenation and perfusion have been identified
      as common pathways to the development and progression of renal disease. Recently,
      the sensitivity of hemodynamic response imaging (HRI) was demonstrated; this is a
      functional magnetic resonance imaging (MRI) method combined with transient
      hypercapnia and hyperoxia for the evaluation of renal perfusion and vascular
      reactivity. The aim of this study was to utilize HRI for the noninvasive
      evaluation of changes in renal hemodynamics and morphology during acute, chronic
      and acute-on-chronic renal failures. METHODS: Renal-HRI maps and true fast
      imaging with steady-state precession (True-FISP) images were used to evaluate
      renal perfusion, morphology and corticomedullary differentiation (CMD). MR images
      were acquired on two mouse models of kidney injury: adenine-induced chronic
      kidney disease (CKD) and rhabdomyolysis-induced acute kidney injury (AKI). Serum
      urea was measured from these mice in order to determine renal function. RESULTS:
      Renal-HRI maps revealed a blunted response to hypercapnia and hyperoxia with
      evolving kidney dysfunction in both models, reflecting hampered renal vascular
      reactivity and perfusion. True-FISP images showed a high sensitivity to renal
      morphological changes, with different patterns characterizing each model.
      Calculated data obtained from HRI and True-FISP during the evolution of renal
      failure and upon recovery, with and without protective intervention, closely
      correlated with the degree of renal impairment. CONCLUSIONS: This study suggests
      the potential combined usage of two noninvasive MRI methods, HRI and True-FISP,
      for the assessment of renal dysfunction without the potential risk associated
      with contrast-agents administration. HRI may also serve as a research tool in
      experimental settings, revealing the hemodynamic changes associated with kidney
      dysfunction.

PMID- 24662014
TI  - Effects of vegetation type on microbial biomass carbon and nitrogen in subalpine
      mountain forest soils.
AB  - BACKGROUND/PURPOSE: Microbial biomass plays an important role in nutrient
      transformation and conservation of forest and grassland ecosystems. The objective
      of this study was to determine the microbial biomass among three vegetation types
      in subalpine mountain forest soils of Taiwan. METHODS: Tatachia is a typical high
      altitude subalpine temperate forest ecosystem in Taiwan with an elevation of 1800
      3952 m and consists of three vegetation types: spruce, hemlock, and grassland.
      Three plots were selected in each vegetation type. Soil samples were collected
      from the organic layer, topsoil, and subsoil. Microbial biomass carbon (Cmic) was
      determined by the chloroform fumigation-extraction method, and microbial biomass
      nitrogen (Nmic) was determined from the total nitrogen (Ntot) released during
      fumigation-extraction. Bacteria, actinomycetes, fungi, cellulolytic microbes,
      phosphate-solubilizing microbes, and nitrogen-fixing microbes were also counted.
      RESULTS: The Cmic and Nmic were highest in the surface soil and declined with the
      soil depth. These were also highest in spruce soils, followed by in hemlock
      soils, and were lowest in grassland soils. Cmic and Nmic had the highest values
      in the spring season and the lowest values in the winter season. Cmic and Nmic
      had significantly positive correlations with total organic carbon (Corg) and
      Ntot. Contributions of Cmic and Nmic, respectively, to Corg and Ntot indicated
      that the microbial biomass was immobilized more in spruce and hemlock soils than
      in grassland soils. Microbial populations of the tested vegetation types
      decreased with increasing soil depth. CONCLUSION: Cmic and Nmic were high in the
      organic layer and decreased with the depth of layers. These values were higher
      for spruce and hemlock soils than for grassland soils. Positive correlations were
      observed between Cmic and Nmic and between Corg and Ntot.

PMID- 24662015
TI  - Evaluation of a modified direct agar proportion method for testing susceptibility
      of Mycobacterium tuberculosis from MGIT samples.
AB  - BACKGROUND/PURPOSE: The emergence of resistance to anti-tuberculosis (TB) drugs
      has become an obstacle to effective TB control. Thus, there is an urgent need to
      identify patients and initiate adequate treatment for drug-resistant cases in a
      timely manner. The BACTEC MGIT 960 system is well known for its rapid culturing
      time, and is in widespread use in Taiwan. In this study, we evaluated the
      possibility of replacing the traditional indirect agar proportion method with a
      modified direct agar proportion method (MDAPM), as a technique for rapid testing
      the drug susceptibility of Mycobacterium tuberculosis without additional cost.
      METHODS: In this study, 432 positive MGIT 960 samples that were identified as M.
      tuberculosis complex using the MeDiPro M. tuberculosis Antigen Rapid Test or the
      Cobas Amplicor MTB test were evaluated. Each sample was tested separately by the
      MDAPM and indirect agar proportion method, between July 2008 and December 2008,
      to compare the consistency and total turnaround time. RESULTS: Four first-line
      anti-TB drugs-rifampin, isoniazid, ethambutol, and streptomycin-were tested. For
      the MDAPM and indirect agar proportion method, the respective consistencies for
      each drug were 99.31%, 98.38%, 98.38%, and 97.22%. Our results also indicated
      that the MDAPM leads to an average saving in working time of 2 weeks, compared
      with the traditional indirect agar proportion method. CONCLUSION: In addition to
      having the potential to shorten turnaround time without compromising diagnostic
      quality, the MDAPM also provides a more efficient and cost-effective procedure.
      This modified procedure presents potential benefits for TB diagnosis in
      laboratories already equipped with the MGIT 960 system.

PMID- 24662016
TI  - Carbapenem-resistant Pseudomonas aeruginosa in Taiwan: Prevalence, risk factors,
      and impact on outcome of infections.
AB  - BACKGROUND: The prevalence and clinical impact on mortality of carbapenem
      resistant Pseudomonas aeruginosa (CRPA) is unclear in Taiwan. We aim to clarify
      these clinical issues by using data from the Taiwan Surveillance of Antimicrobial
      Resistance (TSAR) program. METHODS: Patients from five hospitals with their P.
      aeruginosa isolates collected by TSAR II-VII (2000-2010) program were considered
      as the potential study population. All patients with CRPA were enrolled as case
      patients. Patients with carbapenem-susceptible P. aeruginosa were randomly
      selected in a 1:1 ratio to case patients as control patients. CRPA isolates were
      tested for the presence of carbapenemase-producing genes. The clinical data were
      collected to identify risk factors for CRPA carriage and mortality of P.
      aeruginosa infection. RESULTS: The overall prevalence of CRPA was 10.2%
      (349/3408), which increased significantly by the TSAR period (p = 0.007). Among
      the 164 enrolled patients, the risk factor for carrying CRPA was previous
      fluoroquinolone exposure (p = 0.004). The risk factors for mortality among 80
      patients with infection by P. aeruginosa included: intensive care unit (ICU)
      setting, receipt of antifungal therapy, and presence of invasive devices (p =
      0.001, 0.010, and 0.017; respectively). Carbapenem resistance did not play a
      role. Among the 82 CRPA isolates enrolled in this study, 15 isolates were found
      to carry carbapenemase-producing genes. CONCLUSION: In Taiwan, the prevalence of
      CRPA and carriage of carbapenemase-producing genes was high. However, carbapenem
      resistance did not play a role in the mortality of patients with P. aeruginosa
      infections.

PMID- 24662017
TI  - Comparative in vitro activity of sitafloxacin against bacteremic isolates of
      carbapenem resistant Acinetobacter baumannii complex.
AB  - BACKGROUND: The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB)
      complex has posed a great challenge to clinicians worldwide. Sitafloxacin has
      been shown to have in vitro activity against pathogens resistant to other
      fluoroquinolones. However, data comparing the anti-CRAB activity of sitafloxacin
      with that of other antimicrobial agents are limited. METHODS: Genospecies were
      identified by 16S-23S ribosomal RNA intergenic spacer sequencing. Minimum
      inhibitory concentrations (MICs) were determined by an agar dilution method.
      Isolates with sitafloxacin MICs <= 2 mg/L were provisionally considered as
      susceptible to sitafloxacin. The MIC breakpoint for tigecycline susceptibility
      was 2 mg/L. RESULTS: A total of 167 CRAB complex blood isolates (146 A.
      baumannii, 7 Acinetobacter pittii, and 14 Acinetobacter nosocomialis) were
      collected from January 2009 to December 2011. Around 90% of the A. baumannii
      isolates were resistant to amikacin, cefepime, ceftazidime,
      piperacillin/tazobactam, ampicillin/sulbactam, ciprofloxacin, and levofloxacin.
      By contrast, the rate of resistance to colistin, sitafloxacin, and tigecycline
      was relatively low (0%, 41.1%, and 65.1%, respectively). The MIC50 and MIC90 of
      ciprofloxacin, levofloxacin, and sitafloxacin were 128 mg/L and >128 mg/L; 16
      mg/L and 64 mg/L; 2 mg/L and 8 mg/L, respectively. Compared with ciprofloxacin
      and levofloxacin, sitafloxacin had a significantly lower MIC (p < 0.001), and the
      rate of resistance to sitafloxacin was significantly lower than that to
      ciprofloxacin (97.9% vs. 41.1%, p < 0.001), levofloxacin (97.3% vs. 41.1%, p <
      0.001), and tigecycline (p < 0.001). CONCLUSION: Sitafloxacin has acceptable in
      vitro activity against CRAB, even against isolates resistant to other
      fluoroquinolones. Sitafloxacin may be considered an alternative drug of choice in
      treating CRAB related infections.

PMID- 24662018
TI  - Immunization with antigenic extracts of Leishmania associated with Montanide ISA
      763 adjuvant induces partial protection in BALB/c mice against Leishmania
      (Leishmania) amazonensis infection.
AB  - BACKGROUND/PURPOSE: A proper adjuvant has a relevant role in vaccine formulations
      to generate an effective immune response. In this study, total Leishmania antigen
      (TLA) formulated with Montanide ISA 763 or R848 as adjuvants were evaluated as a
      first generation Leishmania vaccine in a murine model. METHODS: Immunization
      protocols were tested in BALB/c mice with a subcutaneous prime/boost regimen with
      an interval of 3 weeks. Mice immunized with unadjuvanted TLA and phosphate
      buffered saline (PBS) served as control groups. On Day 21 and Day 36 of the
      protocol, we evaluated the humoral immune response induced by each formulation.
      Fifteen days after the boost, the immunized mice were challenged with 1 * 10(5)
      promastigotes of Leishmania (Leishmania) amazonensis in the right footpad (RFP).
      The progress of the infection was followed for 10 weeks; at the end of this
      period, histopathological studies were performed in the RFP. RESULTS: Vaccines
      formulated with Montanide ISA 763 generated an increase in the production of
      immunoglobulin G (IgG; p < 0.05) compared with the control group. There were no
      statistically significant differences in IgG1 production between the study
      groups. However, immunization with TLA-Montanide ISA 763 resulted in an increase
      in IgG2a compared to the unadjuvanted control (p < 0.001). Also noteworthy was
      the fact that a significant reduction in swelling and histopathological damage of
      the RFP was recorded with the Montanide ISA 763 formulation. CONCLUSION: We
      conclude that the immunization of BALB/c mice with a vaccine formulated with TLA
      and Montanide ISA 763 generated a protective immune response against L. (L.)
      amazonensis, characterized by an intense production of IgG2a.

PMID- 24662019
TI  - Correlation of ovalbumin of egg white components with allergic diseases in
      children.
AB  - BACKGROUND: Immunoglobulin E (IgE)-mediated food allergy, such as egg white
      allergy, is common in young children (<3 years old), but not all young children
      sensitive to egg white present with allergic symptoms. This study investigated
      the relationship between sensitization to egg white component allergens and
      clinical manifestations of allergic diseases in young children. METHODS: From
      March to December 2010, 2256 children with physician-diagnosed allergic diseases
      were tested for serum levels of egg white, ovalbumin, and ovomucoid-specific IgE
      in the Pediatric Allergy and Asthma Center of Chang Gung Memorial Hospital. Serum
      was analyzed for specific IgE antibodies to egg white, ovalbumin, and ovomucoid
      by ImmunoCAP (Phadia, Uppsala, Sweden). Allergen-specific IgE levels >=0.35 kUA/L
      were defined as positive. RESULTS: There was a significantly higher sensitization
      rate to egg white and its components in children aged 2-4 years old. The
      sensitization rate to egg white, ovalbumin, and ovomucoid in this age group was
      53.5%, 48.3%, and 37.2%, respectively, and the trend of the sensitization
      decreased with age (p < 0.001). After adjusting for age, sensitization to egg
      white and ovalbumin was associated with children with dermatitis [egg white: odds
      ratio (OR) = 1.28, 95% confidence intervals (CI) = 1.03-1.58, p < 0.05;
      ovalbumin: OR = 1.30, 95% CI = 1.04-1.62, p < 0.05]. Children with ovomucoid
      sensitization had no statistically significant risk among different groups in the
      current study. CONCLUSION: Children aged 2-4 years old have higher sensitivity to
      egg white, ovalbumin, and ovomucoid. Children with egg white and ovalbumin
      sensitization have a higher risk for atopic dermatitis, and ovalbumin has a more
      important contribution. Furthermore, we suggested that in children with atopic
      dermatitis, if they are aged 2-4 years old and are having egg white and ovalbumin
      sensitization, avoiding eating raw or slightly heated eggs might have a
      beneficial effect.

PMID- 24662020
TI  - Hypersensitivity to mosquito bites as the primary clinical manifestation of an
      Epstein-Barr virus infection.
AB  - Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by
      intense local skin reactions with general symptoms, such as high fever and
      regional lymphadenopathy after mosquito bites. Epstein-Barr virus (EBV) chronic
      infection and NK cell lymphoproliferative disease have been reported first in
      diagnosed HMB patients. Here, we present the case of a 6-year-old girl with 2
      months' history of bullae and necrotic skin lesions, accompanied by a high
      temperature, visual hallucinations, and liver dysfunction after mosquito bites. A
      histopathologic examination of the skin lesion showed vasculitis and EBV
      infection. We could not detect any findings of hematologic malignancies or NK
      cell proliferative disease in the patient. Clinicians should closely evaluate HMB
      patients for possible development of lymphoproliferative status or hematologic
      malignant disorders. 

PMID- 24662021
TI  - Melanosome transfer: it is best to give and receive.
AB  - The pigmentation of skin and hair in mammals is driven by the creation within
      melanocytes of melanosomes, a specialized pigment-producing organelle, and the
      subsequent intercellular transfer of this organelle to keratinocytes. This latter
      process is absolutely required for visible pigmentation and effective photo
      protection because it serves to disperse the pigment in skin and hair. Therefore,
      the transfer of melanosomes from the melanocyte to the keratinocyte is as
      important for the biological endpoint of mammalian pigmentation as the biogenesis
      of this fascinating organelle. Here we review new findings that shed light on,
      and raise additional questions about, the mechanism of this enigmatic process. 

PMID- 24662022
TI  - Embracing the void--how much do we really know about targeting and translocation
      to the endoplasmic reticulum?
AB  - In order for a protein to enter the secretory pathway, two crucial steps must
      occur: it first needs to be targeted to the cytosolic surface of the endoplasmic
      reticulum (ER), and then be translocated across the ER membrane. Although for
      many years studies of targeting focused on the signal recognition particle,
      recent findings reveal that several alternative targeting pathways exist, some
      still undescribed, and some only recently elucidated. In addition, many genes
      implicated in the translocation step have not been assigned a specific function.
      Here, we will focus on the open questions regarding ER targeting and
      translocation, and discuss how combining classical biochemistry with systematic
      approaches can promote our understanding of these essential cellular steps. 

PMID- 24662023
TI  - Bone morphogenetic protein-12 induces tenogenic differentiation of mesenchymal
      stem cells derived from equine amniotic fluid.
AB  - Tendon injuries are common in race horses, and mesenchymal stem cells (MSCs)
      isolated from adult and foetal tissue have been used for tendon regeneration. In
      the present study, we evaluated equine amniotic fluid (AF) as a source of MSCs
      and standardised methodology and markers for their in vitro tenogenic
      differentiation. Plastic-adherent colonies were isolated from 12 of 20 AF samples
      by day 6 after seeding and 70-80% cell confluency was reached by day 17. These
      cells expressed mesenchymal surface markers [cluster of differentiation (CD)73,
      CD90 and CD105] by reverse transcription (RT)-polymerase chain reaction (PCR) and
      immunocytochemistry, but did not express haematopoietic markers (CD34, CD45 and
      CD14). In flow cytometry, the expression of CD29, CD44, CD73 and CD90 was
      observed in 68.83 +/- 1.27, 93.66 +/- 1.80, 96.96 +/- 0.44 and 93.7 +/- 1.89% of
      AF-MSCs, respectively. Osteogenic, chondrogenic and adipogenic differentiation of
      MSCs was confirmed by von Kossa and Alizarin red S, Alcian blue and oil red O
      staining, respectively. Upon supplementation of MSC growth media with 50 ng/ml
      bone morphogenetic protein (BMP)-12, AF-MSCs differentiated to tenocytes within
      14 days. The differentiated cells were more slender, elongated and spindle shaped
      with thinner and longer cytoplasmic processes and showed expression of
      tenomodulin and decorin by RT-PCR and immunocytochemistry. In flow cytometry,
      96.7 +/- 1.90 and 80.9 +/- 6.4% of differentiated cells expressed tenomodulin and
      decorin in comparison to 1.6 and 3.1% in undifferentiated control cells,
      respectively. Our results suggest that AF is an easily accessible and effective
      source of MSCs. On BMP-12 supplementation, AF-MSCs can be differentiated to
      tenocytes, which could be exploited for regeneration of ruptured or damaged
      tendon in race horses.

PMID- 24662024
TI  - Quantitative assessment of hsp70, IL-1beta and TNF-alpha in the spinal cord of
      dogs with E40K SOD1-associated degenerative myelopathy.
AB  - Inflammation is involved in the pathogenesis of many neurodegenerative diseases.
      Canine degenerative myelopathy (DM) is a progressive adult-onset
      neurodegenerative disease commonly associated with an E40K missense mutation in
      the SOD1 gene. DM has many similarities to some familial forms of human
      amyotrophic lateral sclerosis (ALS) and may serve as an important disease model
      for therapy development. Pro-inflammatory mediators such as interleukin (IL)
      1beta, tumor necrosis factor (TNF)-alpha and heat shock protein (hsp) 70 play a
      role in the pathogenesis of ALS. The focus of the current work was to determine
      whether an inflammatory phenotype is present in canine DM as defined by IL-1beta,
      TNF-alpha, and hsp70 responses in cerebrospinal fluid (CSF) and spinal cord
      tissue. Concentrations of hsp70, IL-1beta and TNF-alpha were below the limits of
      detection by ELISA in the CSF of both normal and DM-affected dogs.
      Immunohistochemical staining for hsp70 was significantly increased in ependymal
      cells lining the spinal cord central canal of DM-affected dogs (P = 0.003). This
      was not associated with increased IL-1beta or TNF-alpha staining, but was
      associated with increased CD18 staining in the gray matter of DM-affected dogs.
      These results suggest that hsp70 in spinal cord tissue is a potential
      inflammatory signature in canine DM.

PMID- 24662025
TI  - Markers of hepatic regeneration associated with surgical attenuation of
      congenital portosystemic shunts in dogs.
AB  - Dogs with congenital portosystemic shunts (CPSS) have liver hypoplasia and
      hepatic insufficiency. Surgical CPSS attenuation results in liver growth
      associated with clinical improvement. The mechanism of this hepatic response is
      unknown, although liver regeneration is suspected. This study investigated
      whether markers of liver regeneration were associated with CPSS attenuation. Dogs
      treated with CPSS attenuation were prospectively recruited. Residual liver tissue
      was collected for gene expression analysis (seven genes) from 24 CPSS dogs that
      tolerated complete attenuation, 25 dogs that tolerated partial attenuation and
      seven control dogs. Relative gene expression was measured using quantitative
      polymerase chain reaction (qPCR). Blood samples were collected before, 24 h and
      48 h post-surgery from 36 CPSS dogs and from 10 control dogs. Serum hepatocyte
      growth factor (HGF) concentration was measured using a canine specific enzyme
      linked immunosorbent assay (ELISA). HGF mRNA expression was significantly
      decreased in CPSS compared with control dogs (P = 0.046). There were significant
      increases in HGF (P = 0.050) and methionine adenosyltransferase 2 A (MAT2A; P =
      0.002) mRNA expression following partial CPSS attenuation. Dogs with complete
      attenuation had significantly greater MAT2A (P = 0.024) mRNA expression compared
      with dogs with partial attenuation. Serum HGF concentration significantly
      increased 24 h following CPSS attenuation (P < 0.001). Hepatic mRNA expression of
      two markers of hepatocyte proliferation (HGF and MAT2A) was associated with the
      response to surgery in dogs with CPSS, and serum HGF significantly increased
      following surgery, suggesting hepatocyte proliferation. These findings support
      the concept that hepatic regeneration is important in the hepatic response to
      CPSS surgery.

PMID- 24662026
TI  - 1H magnetic resonance spectroscopy: a review of the current literature and its
      potential utility in veterinary oncology.
AB  - Advanced imaging of veterinary cancer patients has evolved in recent years and
      modalities once limited to human medicine have now been described for diagnostic
      purposes in veterinary medicine (positron emission tomography/computed
      tomography, single-photon emission computed tomography, whole body magnetic
      resonance imaging). Magnetic resonance spectroscopy (MRS) is a non-invasive and
      non-ionizing technique that is well described in the human medical literature and
      is most frequently used to evaluate the metabolic activity of tissues with
      questionable malignant transformation. Differentiation of neoplastic tissue from
      surrounding normal tissue is dependent on variations in cellular metabolism.
      Positive identification of malignancy can be made when neoplastic alterations are
      occurring at the cellular level prior to gross anatomic changes. This improved,
      early detection of cancer occurrence (or recurrence) can improve patient survival
      and direct medical therapy. MRS techniques are largely underutilized in
      veterinary medicine, with current research predominantly limited to the brain
      (both evaluation of normal and diseased tissue). Given the clinical utility of
      MRS in humans, the technique may also be useful in the staging of cancer in
      veterinary medicine. 

PMID- 24662027
TI  - Pegylated feline granulocyte colony-stimulating factor increases neutrophil
      levels in cats.
AB  - Neutropenia can often be corrected by treatment with granulocyte-colony
      stimulating factor (G-CSF) and off-label use of commercial human G-CSF (HuG-CSF)
      is a commonly used treatment for neutropenic animals. However, long-term HuG-CSF
      treatment can be associated with adverse effects, including neutropenia. Here,
      feline (Fe) G-CSF was produced in Pichia pastoris, pegylated (Peg) FeG-CSF and
      tested in cats. A randomized controlled clinical trial was conducted to evaluate
      the efficacy of PegFeG-CSF compared to FeG-CSF or HuG-CSF in FIV-infected (n=14),
      FIV-uninfected healthy cats (n=19), and in HuG-CSF-induced neutropenic cats
      (n=4). Daily FeG-CSF doses induced higher neutrophil production than HuG-CSF
      after the second week of treatment (P ? 0.002). Weekly doses of PegFeG-CSF
      induced higher neutrophil counts and showed greater sustained activity than
      weekly doses of FeG-CSF. PegFeG-CSF provided the most therapeutic and sustainable
      neutrophil production (P<0.001) in both FIV-uninfected and FIV-infected cats,
      without the development of neutralizing antibodies. Conversely, all HuG-CSF
      treated cats developed neutralizing antibodies, suggesting cross-reactive
      antibodies to endogenous G-CSF in a majority of the cases with severe
      neutropenia. Strikingly, when PegFeG-CSF was used to rescue cats with HuG-CSF
      induced neutropenia, clinically normal neutrophil numbers returned. Thus, PegFeG
      CSF appears to be a superior treatment for neutropenia in feline patients.

PMID- 24662028
TI  - Proactive rectal warming during total-gland prostate cryoablation.
AB  - PURPOSE: Proactive rectal warming (PRW), as a modification of prostate
      cryoablation, was assessed in terms of rectal complications and therapeutic
      outcomes. MATERIALS AND METHODS: A cohort of 166 patients cumulatively treated
      between September, 2009 and November, 2012 qualified for study, each undergoing
      total-gland cryoablation (TGC) for prostate cancer. The initial 100 patients
      accrued submitted to TGC alone. PRW was administered to the final 66 patients.
      Preemptive warming is achieved by inserting a cryoprobe midline through perineal
      skin into anterior rectal wall under ultrasound guidance. The activated probe
      generates warmth as the ice ball encroaches on rectum. Prospective, post-ablative
      grading of rectal pain was measured at weeks 1, 2, 4, 8, 12, and 24 by using the
      Common Terminology Criteria for Adverse Events. Recurrent prostate cancer was
      gauged by Phoenix criterion (nadir+2 ng/ml). The Mann-Whitney U test and Chi
      square test were used to compare clinical characteristics of therapeutic subsets.
      The Cox proportional hazard model was applied for comparison of cancer recurrence
      risk by group. RESULTS: Rectal pain (all grades) was experienced by patients
      treated with (62%) and without (74%) PRW. Although such pain typically resolved
      with time, it was milder (general lineal model, p=0.023) and less prolonged
      (median: 0.75 vs 1.5 months; log-rank test, p=0.002) in patients receiving PRW
      than in controls. Of note, PRW did not heighten cancer recurrence risk (hazard
      ratio=1.3 [95% CI, 0.3-5.0]). CONCLUSIONS: PRW helps to protect the rectum from
      freeze injury during prostate cryoablation, significantly reducing post-ablative
      rectal pain without compromising therapeutic outcomes.

PMID- 24662029
TI  - Esterified glucomannan improves aflatoxin-induced damage of sperm parameters
      during liquid storage of ram semen at 5 degrees C.
AB  - The aim of the present work was to study the effects of aflatoxin (AF) on sperm
      parameters in rams, and to determine the protective efficiency of esterified
      glucomannan (EG) co-administered with AF up to 96 h of the liquid storage of ram
      semen at 5 degrees C. Thirty-two Merino rams (12-14 months old) were used. The
      animals were examined for their general health status. To ensure their adaptation
      to the environment and the new feeding regimen, a 15-day acclimatization
      programme was applied to the animals, prior to the start of the study.
      Experimental feeding was continued for ninety-two days. The experimental design
      consisted of four dietary treatments. The control group (C) was fed with
      commercial feed. The AF group was fed with commercial feed plus 250 MUg/day of
      total AF. The EG group received commercial feed plus 2g/day of EG. The AF + EG
      group was given commercial feed plus 250 MUg/day of total AF and 2g/day of EG. In
      the study, ejaculates were obtained from rams twice a week for 12 weeks, using an
      electro-ejaculator. After collected, the ejaculates were diluted with a skimmed
      milk extender, and stored at 5 degrees C. Sperm motility and rates of abnormal
      and nonviable spermatozoa were determined for the different treatment groups at 5
      degrees C at 0, 24, 48, 72 and 96 h of liquid storage. During the first two weeks
      of the trial, the groups did not statistically differ from each other for sperm
      motility or rates of abnormal and nonviable spermatozoa at 0, 24, 48 and 96 h of
      storage. As from the third week, the short-term storage of semen produced
      statistically significant differences between the AF group and the other
      treatment groups for sperm parameters (p<0.05). The administration of aflatoxin
      was observed to have reduced sperm motility and to have increased the rates of
      abnormal and nonviable spermatozoa in comparison to the control group (p<0.05),
      while EG co-administered with AF was determined to have ameliorated the adverse
      effects of AF on sperm parameters, and this ameliorative effect continued
      throughout the short-term storage of semen. On the other hand, aflatoxin
      administration resulted in the deterioration of the sperm parameters in the
      following weeks, and the combined administration of EG + AF reversed this adverse
      effect, thus, bringing the sperm parameters closer to the values of the control
      group. This study demonstrated that, in rams, AF adversely affected sperm,
      biochemical and testis parameters, and that the combined administration of EG and
      AF reversibly improved these adverse effects.

PMID- 24662030
TI  - Survivals of mouse oocytes approach 100% after vitrification in 3-fold diluted
      media and ultra-rapid warming by an IR laser pulse.
AB  - Vitrification is the most sought after route to the cryopreservation of animal
      embryos and oocytes and other cells of medical, genetic, and agricultural
      importance. Current thinking is that successful vitrification requires that cells
      be suspended in and permeated by high concentrations of protective solutes and
      that they be cooled at very high rates to below -100 degrees C. We report here
      that neither of these beliefs holds for mouse oocytes. Rather, we find that if
      mouse oocytes are suspended in media that produce considerable osmotic
      dehydration before vitrification and are subsequently warmed at ultra high rates
      (10,000,000 degrees C/min) achieved by a laser pulse, nearly 100% will survive
      even when cooled rather slowly and when the concentration of solutes in the
      medium is only 1/3rd of standard.

PMID- 24662031
TI  - Recombinant Dendroides canadensis antifreeze proteins as potential ingredients in
      cryopreservation solutions.
AB  - Expanding cryopreservation methods to include a wider range of cell types, such
      as those sensitive to freezing, is needed for maintaining the viability of cell
      based regenerative medicine products. Conventional cryopreservation protocols,
      which include use of cryoprotectants such as dimethylsulfoxide (Me2SO), have not
      prevented ice-induced damage to cell and tissue matrices during freezing. A
      family of antifreeze proteins (AFPs) produced in the larvae of the beetle,
      Dendroides canadensis allow this insect to survive subzero temperatures as low as
      -26 degrees C. This study is an assessment of the effect of the four hemolymph D.
      canadensis AFPs (DAFPs) on the supercooling (nucleating) temperature, ice
      structure patterns and viability of the A10 cell line derived from the thoracic
      aorta of embryonic rat. Cryoprotectant solution cocktails containing combinations
      of DAFPs in concentrations ranging from 0 to 3mg/mL in Unisol base mixed with 1M
      Me2SO were first evaluated by cryomicroscopy. Combining multiple DAFPs
      demonstrated significant supercooling point depressing activity (~9 degrees C)
      when compared to single DAFPs and/or conventional 1M Me2SO control solutions.
      Concentrations of DAFPs as low as 1 MUg/mL were sufficient to trigger this
      effect. In addition, significantly improved A10 smooth muscle cell viability was
      observed in cryopreservation experiments with low DAFP-6 and DAFP-2
      concentrations in combination with Me2SO. No significant improvement in viability
      was observed with either DAFP-1 or DAFP-4. Low and effective DAFP concentrations
      are advantageous because they minimize concerns regarding cell cytotoxicity and
      manufacturing cost. These findings support the potential of incorporating DAFPs
      in solutions used to cryopreserve cells and tissues.

PMID- 24662032
TI  - Development of a new microfluidic platform integrating co-cultures of intestinal
      and liver cell lines.
AB  - We developed a new biological model to mimic the organ-organ interactions between
      the intestine and the liver. We coupled polycarbonate cell culture inserts and
      microfluidic biochips in an integrated fluidic platform allowing dynamic co
      cultures (called IIDMP for Integrated Insert in a Dynamic Microfluidic Platform).
      The intestinal compartment was simulated using Caco-2 TC7 cells and the liver one
      by HepG2 C3A. We showed that Caco-2 TC7 viability, barrier integrity and
      functionality (assessed by paracellular and active transport), were not altered
      during co-cultures in the bioreactor in comparison with the conventional insert
      Petri cultures. In parallel, the viability and metabolism of the HepG2 C3A cells
      were maintained in the microfluidic biochips. Then, as proof of concept, we used
      the bioreactor to follow the transport of phenacetin through the intestinal
      barrier and its metabolism into paracetamol by the CYP1A of the HepG2 C3A cells.
      Our results demonstrated the performance of this bioreactor with cell co-cultures
      compared to static co-culture controls in which weak biotransformation into
      paracetamol was detected. Our study illustrated the interest of such a bioreactor
      combining the advantages of a cell culture barrier and of liver microfluidic
      cultures in a common framework for in vitro studies. 

PMID- 24662033
TI  - Drug resistance and secondary treatment of ischaemic stroke: The genetic
      component of the response to acetylsalicylic acid and clopidogrel.
AB  - INTRODUCTION: Cerebrovascular diseases are among the leading causes of death and
      disability in developed countries. Acetylsalicylic acid (ASA) and clopidogrel are
      the most widely-used antiplatelet drugs for secondary prevention of recurrent
      thromboembolic events. However, there have been cases in which antiplatelet drugs
      did not inhibit platelet activity; this phenomenon is called resistance, and it
      may be modulated at the genetic level. DEVELOPMENT: Following a literature
      search, we reviewed the current state of antiplatelet therapy and covered the
      different types of resistance to antiplatelet therapy, how it is measured,
      current problems and limitations, and any genetic factors that have been
      associated with resistance. We mainly used the Genome Wide Association Studies in
      the field of ASA and clopidogrel resistance. CONCLUSIONS: We observed an
      association between different genetic factors and antiplatelet drug resistance as
      measured by platelet activity. However, there is no evident association between
      these genetic factors and risk of new thromboembolic events.

PMID- 24662034
TI  - Integrative clinical transcriptomics analyses for new therapeutic intervention
      strategies: a psoriasis case study.
AB  - Psoriasis is a chronic inflammatory skin disease with complex pathological
      features and unmet pharmacotherapy needs. Here, we present a framework for
      developing new therapeutic intervention strategies for psoriasis by utilizing
      publicly available clinical transcriptomics data sets. By exploring the
      underlying molecular mechanisms of psoriasis, the effects of subsequent
      perturbation of these mechanisms by drugs and an integrative analysis, we propose
      a psoriasis disease signature, identify potential drug repurposing opportunities
      and present novel target selection methodologies. We anticipate that the outlined
      methodology or similar approaches will further support biomarker discovery and
      the development of new drugs for psoriasis. 

PMID- 24662035
TI  - Considering a new paradigm for Alzheimer's disease research.
AB  - Using Alzheimer's disease as a case study, this review argues that it might be
      time to consider a new paradigm in medical research and drug discovery. The
      existing framework is overly dependent on often unvalidated animal models,
      particularly transgenic mice. Translational success remains elusive and costly
      late-stage drug failure is common. The conventional paradigm tends to overlook
      species differences and assumes that animal-based findings are generally
      applicable to humans. Could pathways-based research using advanced human-specific
      models probed with new tools, including those of systems biology, take centre
      stage? The current transition in chemical toxicology to a 21st-century paradigm
      could be a model for health research, with probable medical and economic
      benefits. 

PMID- 24662037
TI  - Ethics issues.

PMID- 24662036
TI  - Transcriptional dysregulation in Huntington's disease: a failure of adaptive
      transcriptional homeostasis.
AB  - Huntington's disease (HD) is a signature polyglutamine disorder. An enduring
      theory of HD pathogenesis has involved dysregulation of transcription. Indeed,
      transcriptional regulatory proteins can be modulated to overcome cardinal
      features of HD-modeled mice, and efforts to move these into human studies are
      ongoing. Here, we discuss a unifying hypothesis emerging from these studies,
      which is that HD represents the pathological disruption of evolutionarily
      conserved adaptive gene programs to counteract oxidative stress, mitochondrial
      dysfunction and accumulation of misfolded proteins. Transcriptional
      dyshomeostasis of adaptive genes is further exacerbated by repression of genes
      involved in normal synaptic activity or growth factor signaling.

PMID- 24662038
TI  - Distinct systemic and central nervous system disease patterns in enterovirus and
      parechovirus infected children.
AB  - OBJECTIVES: Enteroviruses (EV) and human parechoviruses (HPeV) infections are
      increasingly identified in neonates and young children with sepsis, meningitis
      and encephalitis. We investigated EV and HPeV viral loads in plasma and
      cerebrospinal fluid (CSF) among those presenting with sepsis or central nervous
      system (CNS) disease to gain understanding of the nature of these infections.
      METHODS: Detections frequencies and viral loads of EV and HPeV RNA were compared
      in plasma and CSF obtained from infected children originally identified on sepsis
      or CNS screening. RESULTS: Two distinct infection profiles were identified; 11
      subjects with CNS disease, showed higher or similar viral loads in CSF than in
      plasma (median plasma:CSF ratio 0.5), whereas 14 children with sepsis showed low
      or undetectable viral loads in CSF and high viral loads in plasma (mean ratio
      5700). HPeV type 3 and one EV serotype (coxsackievirus B2) were primarily
      associated with the latter presentation. CONCLUSIONS: Simple detection of EV or
      HPeV RNA in CSF is not predictive of CNS disease, especially in the absence of
      clinical markers (i.e. pleocytosis). Screening of plasma can identify EV and HPeV
      RNA in a substantial proportion of sepsis cases, some of which will be missed if
      CSF samples alone are screened.

PMID- 24662039
TI  - The impact of age and physical activity level on manual aiming performance.
AB  - Older adults traditionally adapt their discrete aiming movements, thereby
      traveling a larger proportion of the movement under closed-loop control. As the
      beneficial impact of a physically active lifestyle in older age has been
      described for several aspects of motor control, we compared the aiming
      performance of young controls to active and sedentary older adults. To
      additionally determine the contribution of visual feedback, aiming movements were
      executed with and without saccades. Results showed only sedentary older adults
      adopted the typical movement changes, highlighting the impact of a physically
      active lifestyle on manual aiming in older age. In an attempt to reveal the
      mechanism underlying the movement changes, evidence for an age-related decline in
      force control was found, which in turn resulted in an adapted aiming strategy.
      Finally, prohibiting saccades did not affect older adults' performance to a
      greater extent, suggesting they do not rely more on visual feedback than young
      controls. 

PMID- 24662040
TI  - The two step nanotube formation on TiZr as scaffolds for cell growth.
AB  - Various TiO2 nanotubes on Ti50Zr alloy have been fabricated via a two step
      anodization method in glycol with 15vol.% H2O and 0.2M NH4F under anodization
      controlled voltages of 15, 30 and 45V. A new sonication treatment in deionized
      water with three steps and total sonication time as 1min was performed after the
      first anodization step in order to remove the oxide layer grown during 2h. The
      second step of anodization was for 1h and took place at the same conditions. The
      role of removed layer as a nano-prepatterned surface was evidenced in the
      formation of highly ordered nanotubular structures and morphological features
      were analyzed by SEM, AFM and surface wettability. The voltage-controlled
      anodization leads to various nanoarhitectures, with diameters in between 20 and
      80nm. As biological assay, cell culture tests with MG63 cell line originally
      derived from a human osteosarcoma were performed. A correlation between
      nanostructure morphological properties as a result of voltage-controlled
      anodization and cell response was established. 

PMID- 24662042
TI  - Plasma viscosity is increased in subjects with elevated ankle brachial index.
AB  - OBJECTIVE: Peripheral artery occlusive disease (PAOD) is associated with
      increased cardiovascular risk (CVR). Recently it has been reported that also the
      increased stiffness of lower limb arteries is associated with increased CVR. In
      particular, subjects with poorly compressible arteries (PCA) appear to have a CVR
      even higher than that of subjects with PAOD. Limited data are available on the
      role of hemorheological factors in determining increase in arterial stiffness.
      Our study aimed to investigate possible association between blood and plasma
      viscosity and elevated ankle brachial index (ABI). METHODS: Subjects were free
      living participants to a cardiovascular disease screening campaign. Sixty-two
      subjects with ABI ranging 1.3-1.4, and 20 with ABI >1.4 were matched with 124 and
      40 control subjects, respectively. Cardiovascular disease risk factors (blood
      pressure, blood lipids, glucose, cigarette smoking, obesity) were evaluated by
      routine methods. Blood and plasma viscosities were measured by a cone-plate
      viscometer. Ankle-brachial index was computed as measure of arterial stiffness.
      RESULTS: Compared with controls, who were carefully matched for age, sex and all
      cardiovascular risk factors, subjects with elevated ABI values had increased
      levels of plasma viscosity (1.42 +/- 0.11 vs. 1.35 +/- 0.10 cP, p <  0.001, for
      subjects with ABI ranging 1.3-1.4, and 1.41 +/- 0.10 vs. 1.33 +/- 0.10 cP, p < 
      0.01, for subjects with ABI >1.4). No difference in blood viscosity was observed.
      CONCLUSION: The present investigation provides evidence that plasma viscosity is
      increased in subjects with elevated ABI values, independently of other
      cardiovascular risk factors. This finding contributes to explain the high CVR of
      patients with PCA.

PMID- 24662043
TI  - Extensive prurigo nodularis: characterization and etiology.
AB  - BACKGROUND/AIMS: Prurigo nodularis (PN) has multiple reported disease
      associations, and this study analyzes the demographics, clinical distribution and
      underlying etiologies in an Asian cohort. METHODS: A 1-year retrospective study
      was carried out on PN patients with extensive lesions (>=10) who attended a
      specialized itch clinic. RESULTS: 37 patients (46% male, median age 53 years)
      were included. In all patients, an underlying etiologic factor associated with
      pruritus could be identified. 49% (n = 18) of patients had a single attributable
      etiology, whilst 51% (n = 19) had multiple etiologies. Among all patients,
      dermatological disease was the most common cause (82%), of which endogenous
      eczema comprised the majority of cases (54%), followed by systemic disease (38%).
      CONCLUSIONS: All patients with extensive PN had identifiable factors associated
      with pruritus in this study, and a dermatological condition was the predominant
      etiology in both patients with mono- and multifactorial disease. A significant
      number of patients had underlying systemic causes.

PMID- 24662044
TI  - Chronic migraine.
AB  - Chronic migraine is a disabling neurologic condition that affects 2% of the
      general population. Patients with chronic migraine have headaches on at least 15
      days a month, with at least eight days a month on which their headaches and
      associated symptoms meet diagnostic criteria for migraine. Chronic migraine
      places an enormous burden on patients owing to frequent headaches;
      hypersensitivity to visual, auditory, and olfactory stimuli; nausea; and
      vomiting. It also affects society through direct and indirect medical costs.
      Chronic migraine typically develops after a slow increase in headache frequency
      over months to years. Several factors are associated with an increased risk of
      transforming to chronic migraine. The diagnosis requires a carefully performed
      patient interview and neurologic examination, sometimes combined with additional
      diagnostic tests, to differentiate chronic migraine from secondary headache
      disorders and other primary chronic headaches of long duration. Treatment takes a
      multifaceted approach that may include risk factor modification, avoidance of
      migraine triggers, drug and non-drug based prophylaxis, and abortive migraine
      treatment, the frequency of which is limited to avoid drug overuse. This article
      provides an overview of current knowledge regarding chronic migraine, including
      epidemiology, risk factors for its development, pathophysiology, diagnosis,
      management, and guidelines. The future of chronic migraine treatment and research
      is also discussed. 

PMID- 24662045
TI  - Importance of juvenile hormone signaling arises with competence of insect larvae
      to metamorphose.
AB  - Juvenile hormone (JH) postpones metamorphosis of insect larvae until they have
      attained an appropriate stage and size. Then, during the final larval instar, a
      drop in JH secretion permits a metamorphic molt that transforms larvae to adults
      either directly (hemimetaboly) or via a pupal stage (holometaboly). In both
      scenarios, JH precludes metamorphosis by activating the Kr-h1 gene through a JH
      receptor, Methoprene-tolerant (Met). Removal of Met, Kr-h1, or JH itself triggers
      deleterious precocious metamorphosis. Although JH is thought to maintain the
      juvenile status throughout larval life, various methods of depleting JH failed to
      induce metamorphosis in early-instar larvae. To determine when does JH signaling
      become important for the prevention of precocious metamorphosis, we chose the
      hemimetabolous bug, Pyrrhocoris apterus, and the holometabolous silkworm, Bombyx
      mori. Both species undergo a fixed number of five larval instars. Pyrrhocoris
      larvae subjected to RNAi-mediated knockdown of Met or Kr-h1 underwent precocious
      adult development when treated during the fourth (penultimate) instar, but
      younger larvae proved increasingly resistant to loss of either gene. The earliest
      instar developing minor signs of precocious metamorphosis was the third.
      Therefore, the JH-response genes may not be required to maintain the larval
      program during the first two larval instars. Next, we examined Bombyx mod mutants
      that cannot synthesize authentic, epoxidized forms of JH. Although mod larvae
      expressed Kr-h1 mRNA at severely reduced levels since hatching, they only entered
      metamorphosis by pupating after four, rarely three instars. Based on findings in
      Pyrrhocoris and Bombyx, we propose that insect postembryonic development is
      initially independent of JH. Only later, when larvae gain competence to enter
      metamorphosis, JH signaling becomes necessary to prevent precocious metamorphosis
      and to optimize growth. 

PMID- 24662046
TI  - Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk
      interface coordinate the transport and assembly of hypopharyngeal structures.
AB  - The vertebrate head-trunk interface (occipital region) has been heavily
      remodelled during evolution, and its development is still poorly understood. In
      extant jawed vertebrates, this region provides muscle precursors for the throat
      and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that
      take a stereotype path rostrally along the pharynx and are thought to reach their
      target sites via active migration. Yet, this projection pattern emerged in
      jawless vertebrates before the evolution of migratory muscle precursors. This
      suggests that a so far elusive, more basic transport mechanism must have existed
      and may still be traceable today. Here we show for the first time that all
      occipital tissues participate in well-conserved cell movements. These cell
      movements are spearheaded by the occipital lateral mesoderm and ectoderm that
      split into two streams. The rostrally directed stream projects along the floor of
      the pharynx and reaches as far rostrally as the floor of the mandibular arch and
      outflow tract of the heart. Notably, this stream leads and engulfs the later
      emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to
      redirect hypobranchial/hypoglossal muscle precursors towards various attractants,
      (ii) placed non-migratory muscle precursors into the occipital environment or
      (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory,
      they still followed the trajectory set by the occipital lateral mesoderm and
      ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic
      movements, driven by the occipital lateral mesoderm and ectoderm, that ensure
      cell transport and organ assembly at the head-trunk interface. 

PMID- 24662047
TI  - Na+ dysregulation coupled with Ca2+ entry through NCX1 promotes muscular
      dystrophy in mice.
AB  - Unregulated Ca(2+) entry is thought to underlie muscular dystrophy. Here, we
      generated skeletal-muscle-specific transgenic (TG) mice expressing the Na(+)
      Ca(2+) exchanger 1 (NCX1) to model its identified augmentation during muscular
      dystrophy. The NCX1 transgene induced dystrophy-like disease in all hind-limb
      musculature, as well as exacerbated the muscle disease phenotypes in delta
      sarcoglycan (Sgcd(-/-)), Dysf(-/-), and mdx mouse models of muscular dystrophy.
      Antithetically, muscle-specific deletion of the Slc8a1 (NCX1) gene diminished
      hind-limb pathology in Sgcd(-/-) mice. Measured increases in baseline Na(+) and
      Ca(2+) in dystrophic muscle fibers of the hind-limb musculature predicts a net
      Ca(2+) influx state due to reverse-mode operation of NCX1, which mediates
      disease. However, the opposite effect is observed in the diaphragm, where NCX1
      overexpression mildly protects from dystrophic disease through a predicted
      enhancement in forward-mode NCX1 operation that reduces Ca(2+) levels. Indeed,
      Atp1a2(+/-) (encoding Na(+)-K(+) ATPase alpha2) mice, which have reduced Na(+)
      clearance rates that would favor NCX1 reverse-mode operation, showed exacerbated
      disease in the hind limbs of NCX1 TG mice, similar to treatment with the Na(+)
      K(+) ATPase inhibitor digoxin. Treatment of Sgcd(-/-) mice with ranolazine, a
      broadly acting Na(+) channel inhibitor that should increase NCX1 forward-mode
      operation, reduced muscular pathology. 

PMID- 24662048
TI  - PGC-1 coactivator activity is required for murine erythropoiesis.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha
      (PGC-1alpha) and PGC-1beta have been shown to be intimately involved in the
      transcriptional regulation of cellular energy metabolism as well as other
      biological processes, but both coactivator proteins are expressed in many other
      tissues and organs in which their function is, in essence, unexplored. Here, we
      found that both PGC-1 proteins are abundantly expressed in maturing erythroid
      cells. PGC-1alpha and PGC-1beta compound null mutant (Pgc-1(c)) animals express
      less beta-like globin mRNAs throughout development; consequently, neonatal Pgc
      1(c) mice exhibit growth retardation and profound anemia. Flow cytometry shows
      that the number of mature erythrocytes is markedly reduced in neonatal Pgc-1(c)
      pups, indicating that erythropoiesis is severely compromised. Furthermore,
      hematoxylin and eosin staining revealed necrotic cell death and cell loss in Pgc
      1(c) livers and spleen. Chromatin immunoprecipitation studies revealed that both
      PGC-1alpha and -1beta, as well as two nuclear receptors, TR2 and TR4,
      coordinately bind to the various globin gene promoters. In addition, PGC-1alpha
      and -1beta can interact with TR4 to potentiate transcriptional activation. These
      data provide new insights into our understanding of globin gene regulation and
      raise the interesting possibility that the PGC-1 coactivators can interact with
      TR4 to elicit differential stage-specific effects on globin gene transcription. 

PMID- 24662049
TI  - Sox17-mediated maintenance of fetal intra-aortic hematopoietic cell clusters.
AB  - During mouse development, definitive hematopoiesis is first detected around
      embryonic day 10.5 (E10.5) in the aorta-gonad-mesonephros (AGM) region, which
      exhibits intra-aortic cell clusters. These clusters are known to contain
      hematopoietic stem cells (HSCs). On the other hand, it is not clear how the cells
      in such clusters maintain their HSC phenotype and how they are triggered to
      differentiate. Here we found that an endodermal transcription factor marker,
      Sox17, and other F-group (SoxF) proteins, Sox7 and Sox18, were expressed in E10.5
      intra-aortic cell clusters. Forced expression of any of these SoxF proteins,
      particularly Sox17, in E10.5 AGM CD45(low) c-Kit(high) cells, which are the major
      component of intra-aortic clusters, led to consistent formation of cell clusters
      in vitro during several passages of cocultures with stromal cells. Cluster
      forming cells with constitutive Sox17 expression retained long-term bone marrow
      reconstitution activity in vivo. Notably, shutdown of exogenously introduced
      Sox17 gene expression resulted in immediate hematopoietic differentiation. These
      results indicate that SoxF proteins, especially Sox17, contribute to the
      maintenance of cell clusters containing HSCs in the midgestation AGM region.
      Furthermore, SoxF proteins play a pivotal role in controlling the HSC fate
      decision between indefinite self-renewal and differentiation during fetal
      hematopoiesis. 

PMID- 24662050
TI  - Phosphoinositide-dependent kinase 1 and mTORC2 synergistically maintain postnatal
      heart growth and heart function in mice.
AB  - The protein kinase Akt plays a critical role in heart function and is activated
      by phosphorylation of threonine 308 (T308) and serine 473 (S473). While
      phosphoinositide-dependent kinase 1 (PDK1) is responsible for Akt T308
      phosphorylation, the identities of the kinases for Akt S473 phosphorylation in
      the heart remain controversial. Here, we disrupted mTOR complex 2 (mTORC2)
      through deletion of Rictor in the heart and found normal heart growth and
      function. Rictor deletion caused significant reduction of Akt S473
      phosphorylation but enhanced Akt T308 phosphorylation, suggesting that a high
      level of Akt T308 phosphorylation maintains Akt activity and heart function.
      Deletion of Pdk1 in the heart caused significantly enhanced Akt S473
      phosphorylation that was suppressed by removal of Rictor, leading to worsened
      dilated cardiomyopathy (DCM) and accelerated heart failure in Pdk1-deficient
      mice. In addition, we found that increasing Akt S473 phosphorylation through
      deletion of Pten or chemical inhibition of PTEN reversed DCM and heart failure in
      Pdk1-deficient mice. Investigation of heart samples from human DCM patients
      revealed changes similar to those in the mouse models. These results demonstrated
      that PDK1 and mTORC2 synergistically promote postnatal heart growth and maintain
      heart function in postnatal mice. 

PMID- 24662051
TI  - Activation of stress response pathways promotes formation of antiviral granules
      and restricts virus replication.
AB  - The formation of protein-RNA granules is a part of both natural cellular function
      (P-bodies and nuclear HNRNPs) and the response to cellular stress (stress
      granules and ND10 bodies). To better understand the role of stress-induced
      granules in viral infection, we have studied the ability of cells to restrict
      poxvirus replication through the formation of antiviral granules (AVGs). Of cells
      infected with a wild-type poxvirus, a small number spontaneously formed AVGs. In
      these AVG-positive cells, viral gene expression was inhibited. The addition of
      compounds that altered RNA helicase activity, induced oxidative stress, or
      stimulated translation initiation factor phosphorylation significantly increased
      the number of AVG-positive cells. When AVGs formed, both viral translation and
      titers were decreased even when host translation persisted. Treatment with the
      antiviral compound isatin beta-thiosemicarbazone (IBT), a compound that was used
      to treat smallpox infections, induced AVGs, suggesting a role for these
      structures in the pharmacological inhibition of poxvirus replication. These
      findings provide evidence that AVGs are an innate host response that can be
      exogenously stimulated to combat virus infection. Since small molecules are able
      to stimulate AVG formation, it is a potential target for new antiviral
      development. 

PMID- 24662052
TI  - Pten null prostate epithelium promotes localized myeloid-derived suppressor cell
      expansion and immune suppression during tumor initiation and progression.
AB  - Chronic inflammation is known to be associated with prostate cancer development,
      but how epithelium-associated cancer-initiating events cross talk to inflammatory
      cells during prostate cancer initiation and progression is largely unknown. Using
      the Pten null murine prostate cancer model, we show an expansion of Gr-1(+)
      CD11b(+) myeloid-derived suppressor cells (MDSCs) occurring intraprostatically
      immediately following epithelium-specific Pten deletion without expansion in
      hematopoietic tissues. This MDSC expansion is accompanied by sustained immune
      suppression. Prostatic Gr-1(+) CD11b(+) cells, but not those isolated from the
      spleen of the same tumor-bearing mice, suppress T cell proliferation and express
      high levels of Arginase 1 and iNOS. Mechanistically, the loss of PTEN in the
      epithelium leads to a significant upregulation of genes within the inflammatory
      response and cytokine-cytokine receptor interaction pathways, including Csf1 and
      Il1b, two genes known to induce MDSC expansion and immunosuppressive activities.
      Treatment of Pten null mice with the selective CSF-1 receptor inhibitor GW2580
      decreases MDSC infiltration and relieves the associated immunosuppressive
      phenotype. Our study indicates that epithelium-associated tumor-initiating events
      trigger the secretion of inflammatory cytokines and promote localized MDSC
      expansion and immune suppression, thereby promoting tumor progression. 

PMID- 24662053
TI  - A retinoblastoma allele that is mutated at its common E2F interaction site
      inhibits cell proliferation in gene-targeted mice.
AB  - The retinoblastoma protein (pRB) is best known for regulating cell proliferation
      through E2F transcription factors. In this report, we investigate the properties
      of a targeted mutation that disrupts pRB interactions with the transactivation
      domain of E2Fs. Mice that carry this mutation endogenously (Rb1(DeltaG)) are
      defective for pRB-dependent repression of E2F target genes. Except for an
      accelerated entry into S phase in response to serum stimulation, cell cycle
      regulation in Rb1(DeltaG/DeltaG) mouse embryonic fibroblasts (MEFs) strongly
      resembles that of the wild type. In a serum deprivation-induced cell cycle exit,
      Rb1(DeltaG/DeltaG) MEFs display a magnitude of E2F target gene derepression
      similar to that of Rb1(-/-) cells, even though Rb1(DeltaG/DeltaG) cells exit the
      cell cycle normally. Interestingly, cell cycle arrest in Rb1(DeltaG/DeltaG) MEFs
      is responsive to p16 expression and gamma irradiation, indicating that alternate
      mechanisms can be activated in G1 to arrest proliferation. Some
      Rb1(DeltaG/DeltaG) mice die neonatally with a muscle degeneration phenotype,
      while the others live a normal life span with no evidence of spontaneous tumor
      formation. Most tissues appear histologically normal while being accompanied by
      derepression of pRB-regulated E2F targets. This suggests that non-E2F-, pRB
      dependent pathways may have a more relevant role in proliferative control than
      previously identified. 

PMID- 24662055
TI  - Baylisascaris potosis n. sp., a new ascarid nematode isolated from captive
      kinkajou, Potos flavus, from the Cooperative Republic of Guyana.
AB  - We describe a new nematode species, Baylisascaris potosis n. sp., isolated from
      captive kinkajou, Potos flavus, from the Cooperative Republic of Guyana. The
      nematode was found in fecal specimens, identified morphologically, and confirmed
      genetically. The new species is similar to Baylisascaris procyonis, Baylisascaris
      columnaris, and other Baylisascaris species, but is distinguished by the position
      of the male phasmidial pole. Nuclear and mitochondrial DNA sequence analyses
      confirmed that the new species is phylogenetically distinct from all the members
      of the genus Baylisascaris, and groups with B. procyonis and B. columnaris. This
      nematode is the 10th species assigned to the genus Baylisascaris. 

PMID- 24662056
TI  - Impairment of hippocampal-dependent memory induced by juvenile high-fat diet
      intake is associated with enhanced hippocampal inflammation in rats.
AB  - In addition to metabolic and cardiovascular disorders, obesity pandemic is
      associated with chronic low-grade inflammation as well as adverse cognitive
      outcomes. However, the existence of critical periods of development that differ
      in terms of sensitivity to the effects of diet-induced obesity remains
      unexplored. Using short exposure to a high-fat diet (HFD) exerting no effects
      when given to adult mice, we recently found impairment of hippocampal-dependent
      memory and plasticity after similar HFD exposure encompassing adolescence (from
      weaning to adulthood) showing the vulnerability of the juvenile period (Boitard
      et al., 2012). Given that inflammatory processes modulate hippocampal functions,
      we evaluated in rats whether the detrimental effect of juvenile HFD (jHFD) on
      hippocampal-dependent memory is associated with over-expression of hippocampal
      pro-inflammatory cytokines. jHFD exposure impaired long-term spatial reference
      memory in the Morris water maze without affecting acquisition or short-term
      memory. This suggests an effect on consolidation processes. Moreover, jHFD
      consumption delayed spatial reversal learning. jHFD intake did neither affect
      basal expression of pro-inflammatory cytokines at the periphery nor in the brain,
      but potentiated the enhancement of Interleukin-1-beta and Tumor Necrosis Factor
      alpha expression specifically in the hippocampus after a peripheral immune
      challenge with lipopolysaccharide. Interestingly, whereas the same duration of
      HFD intake at adulthood induced similar weight gain and metabolic alterations as
      jHFD intake, it did neither affect spatial performance (long-term memory or
      reversal learning) nor lipopolysaccharide-induced cytokine expression in the
      hippocampus. Finally, spatial reversal learning enhanced Interleukin-1-beta in
      the hippocampus, but not in the frontal cortex and the hypothalamus, of jHFD-fed
      rats. These results indicate that juvenile HFD intake promotes exaggerated pro
      inflammatory cytokines expression in the hippocampus which is likely to
      contribute to spatial memory impairment. 

PMID- 24662054
TI  - The Mi-2 homolog Mit1 actively positions nucleosomes within heterochromatin to
      suppress transcription.
AB  - Mit1 is the putative chromatin remodeling subunit of the fission yeast
      Snf2/histone deacetylase (HDAC) repressor complex (SHREC) and is known to repress
      transcription at regions of heterochromatin. However, how Mit1 modifies chromatin
      to silence transcription is largely unknown. Here we report that Mit1 mobilizes
      histone octamers in vitro and requires ATP hydrolysis and conserved chromatin
      tethering domains, including a previously unrecognized chromodomain, to remodel
      nucleosomes and silence transcription. Loss of Mit1 remodeling activity results
      in nucleosome depletion at specific DNA sequences that display low intrinsic
      affinity for the histone octamer, but its contribution to antagonizing RNA
      polymerase II (Pol II) access and transcription is not restricted to these sites.
      Genetic epistasis analyses demonstrate that SHREC subunits and the transcription
      coupled Set2 histone methyltransferase, which is involved in suppression of
      cryptic transcription at actively transcribed regions, cooperate to silence
      heterochromatic transcripts. In addition, we have demonstrated that Mit1's
      remodeling activity contributes to SHREC function independently of Clr3's histone
      deacetylase activity on histone H3 K14. We propose that Mit1 is a chromatin
      remodeling factor that cooperates with the Clr3 histone deacetylase of SHREC and
      other chromatin modifiers to stabilize heterochromatin structure and to prevent
      access to the transcriptional machinery. 

PMID- 24662057
TI  - Correlation of genetic risk and messenger RNA expression in a Th17/IL23 pathway
      analysis in inflammatory bowel disease.
AB  - BACKGROUND: The Th17/IL23 pathway has both genetically and biologically been
      implicated in the pathogenesis of the inflammatory bowel diseases (IBD), Crohn's
      disease, and ulcerative colitis. So far, it is unknown whether and how associated
      risk variants affect expression of the genes encoding for Th17/IL23 pathway
      proteins. METHODS: Ten IBD-associated SNPs residing near Th17/IL23 genes were
      used to construct a genetic risk model in 753 Dutch IBD cases and 1045 controls.
      In an independent cohort of 40 Crohn's disease, 40 ulcerative colitis, and 40
      controls, the genetic risk load and presence of IBD were correlated to
      quantitative PCR-generated messenger RNA (mRNA) expression of 9 representative
      Th17/IL23 genes in both unstimulated and PMA/CaLo stimulated peripheral blood
      mononuclear cells. In 1240 individuals with various immunological diseases with
      whole genome genotype and mRNA-expression data, we also assessed correlation
      between genetic risk load and differential mRNA expression and sought for SNPs
      affecting expression of all currently known Th17/IL23 pathway genes (cis
      expression quantitative trait locus). RESULTS: The presence of IBD, but not the
      genetic risk load, was correlated to differential mRNA expression for IL6 in
      unstimulated peripheral blood mononuclear cells and to IL23A and RORC in response
      to stimulation. The cis-expression quantitative trait locus analysis showed
      little evidence for correlation between genetic risk load and mRNA expression of
      Th17/IL23 genes, because we identified for only 2 of 22 Th17/IL23 genes a cis
      expression quantitative trait locus single nucleotide polymorphism that is also
      associated to IBD (STAT3 and CCR6). CONCLUSIONS: Our results suggest that only
      the presence of IBD and not the genetic risk load alters mRNA expression levels
      of IBD-associated Th17/IL23 genes.

PMID- 24662058
TI  - Reply to Mendall.

PMID- 24662059
TI  - A resorufin-based colorimetric and fluorescent probe for live-cell monitoring of
      hydrazine.
AB  - We report a novel colorimetric and red-emitting fluorescent probe for hydrazine
      detection based on resorufin platform. This OFF-ON fluorescent probe shows a
      large (117nm) red-shifted absorption spectrum and the color changes from
      colorless to red upon addition of hydrazine in the aqueous solution, which can
      serve as a "naked-eye" probe for hydrazine. Moreover, this probe also shows a
      significant fluorescence increase (~16 folds) and excellent linear relationship
      at physiological pH. Utilizing this sensitive and selective probe, we have
      successfully detected hydrazine in living cells. 

PMID- 24662060
TI  - Plasmonic ELISA for the ultrasensitive detection of Treponema pallidum.
AB  - In this report, we have developed a plasmonic ELISA strategy for the detection of
      syphilis. Plasmonic ELISA is an enzyme-linked immunoassay combined with enzyme
      mediated surface plasmon resonance (SPR) of gold nanoparticles (AuNPs). Immune
      response of the Treponema pallidum (T. pallidum) antibodies triggers the
      acetylcholinesterase-catalyzed hydrolysis of acetylthiocholine to produce
      abundant thiocholine. The positive charged thiol, in turn, alters the surface
      charge distribution the AuNPs and leads to the agglomeration of the AuNPs. The
      induced strong localized SPR effect of the agglomerate AuNPs can, thus, allow the
      quantitative assay of T. pallidum antibodies due to the remarkable color and
      absorption spectral response changes of the reaction system. The plasmonic ELISA
      exhibited a quasilinear response to the logarithmic T. pallidum antibody
      concentrations in the range of 1pg/mL-10ng/mL with a detection limit of
      0.98pg/mL. Such a low detection limit was 1000-fold improvements in sensitivity
      over a conventional ELISA. The results of plasmonic ELISA in syphilis assays of
      serum specimens from 60 patients agreed with those obtained using a conventional
      ELISA method. The plasmonic ELISA has characteristics (analyte specific, cost
      effective, ease of automatic, low limit of detection) that provide potential for
      diagnosis and therapeutic monitoring of syphilis. 

PMID- 24662061
TI  - An aggregated perylene-based broad-spectrum, efficient and label-free quencher
      for multiplexed fluorescent bioassays.
AB  - Fluorescent sensing systems based on the quenching of fluorophores have found
      wide applications in bioassays. An efficient quencher will endow the sensing
      system a high sensitivity. The frequently used quenchers are based on organic
      molecules or nanomaterials, which usually need tedious synthesizing and modifying
      steps, and exhibit different quenching efficiencies to different fluorophores. In
      this work, we for the first time report that aggregated perylene derivative can
      serve as a broad-spectrum and label-free quencher that is able to efficiently
      quench a variety of fluorophores, such as green, red and far red dyes labeled on
      DNA. By choosing nucleases as model biomolecules, such a broad-spectrum quencher
      was then employed to construct a multiplexed bioassay platform through a label
      free manner. Due to the high quenching efficiency of the aggregated perylene, the
      proposed platform could detect nuclease with high sensitivity, with a detection
      limit of 0.03U/mL for EcoRV, and 0.05U/mL for EcoRI. The perylene quencher does
      not affect the activity of nuclease, which makes it possible to design post
      addition type bioassay platform. Moreover, the proposed platform allows
      simultaneous and multicolor analysis of nucleases in homogeneous solution,
      demonstrating its value of potential application in rapid screening of multiple
      bio-targets. 

PMID- 24662062
TI  - Sandwiching spherical 1,2-dioleoyltrimethylammoniumpropane liposome in gold
      nanoparticle on solid transducer for electrochemical ultrasensitive DNA detection
      and transfection.
AB  - Cationic N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium propane (DOTAP)
      liposome is spherically sandwiched in gold nanoparticle (abbreviated as sDOTAP
      AuNP) onto a gold electrode surface. The sDOTAP-AuNP is applied for
      electrochemical label free DNA sensing and Escherichia coli cell transfection for
      the first time. Complementary target (named as hybridized), non-complementary
      target (un-hybridized) and single base mismatch target (named as SMM) hybridized
      surfaces are discriminated sensitively and selectively in presence of [Fe(CN)6](3
      /4-). Double strand specific intercalator methylene blue in combination with
      [Fe(CN)6](3-) is used to enhance target detection limit down to femtomolar
      concentration. Cyclic voltammetry (CV), electrochemical impedance spectroscopy
      (EIS), differential pulse voltammetry (DPV) techniques are used for
      characterizing DNA sensing. High Resolution Transmission Electron Microscopy
      (HRTEM), Fourier Transform Infrared Spectroscopy (FTIR), Atomic Force Microscopy
      (AFM) and Dynamic Light Scattering (DLS) techniques are used to confirm the
      spherical nature of the sDOTAP-AuNP-DNA composite in solution and on the solid
      surface. DNA on the sDOTAP-ssDNA is transferred by potential stripping method
      (+0.2V (Ag/AgCl)) into buffer solution containing E. coli cells. The transfection
      is confirmed by the contrast images for the transfected and non-transfected cell
      from Confocal Laser Scanning Microscopy (CLSM). The results demonstrate
      effectiveness of the electrochemical DNA transfection method developed and could
      be applied for other cells. 

PMID- 24662063
TI  - One-pot approach for examining the DNA methylation patterns using an engineered
      methyl-probe.
AB  - Aberrant DNA methylation is a common observation in various types of human
      cancers, i.e., breast and lung cancers. Nevertheless, the current DNA methylation
      detection approaches require bisulfite treatments and are laborious or costly to
      perform. To address these challenges, we developed a methyl-probe based on the
      MBD1 protein. Combined with fluorescence correlation spectroscopy, our probe can
      sensitively detect the existence of DNA methylation at concentrations above 20nM
      in a one-pot assay. The probe can quantify the total amount of methylated CG
      dinucleotides above ~20nM, independent of DNA sequence contexts, concentrations
      (20-1900nM) and methylation levels (5-100%). Our detection platform offers a
      simple and cheap alternative DNA methylation detection approach. 

PMID- 24662064
TI  - An integrated giant magnetoimpedance biosensor for detection of biomarker.
AB  - A Dynabeads-labeled magnetic immunoassay (MIA) has been developed by using an
      integrated giant magnetoimpedance (GMI) biosensor for the detection of alpha
      fetoprotein (AFP). The GMI biosensor (Cr/Cu/NiFe/Cu/NiFe/Al2O3/Cr/Au films)
      integrated magnetic sensing elements and a biomolecular immunoplatform. Au film
      was modified with 11-Mercaptoundecanoic acid (11-MUA) for the immobilization of
      AFP monoclonal antibody. Double antibody sandwich immunoassay was used to
      specifically capture and label AFP antigen. Functionalized Dynabeads were
      conjugated to AFP antigen by streptavidin-biotin binding assay. GMI responses
      were measured for sensitive detection of AFP from 1 to 10ng/ml. Our results
      revealed that the presence of AFP on the biosensor improved the GMI effect owing
      to the induced magnetic dipole of superparamagnetic Dynabeads, and the GMI ratio
      was greatly increased at high frequency. Specificity of MIA was tested through
      the use of 1% bovine serum albumin (BSA). The underlying biophysical mechanisms
      responsible for the enhanced GMI effect in the detection of AFP were discussed.
      This work provides a complex lab-on-chip MIA for the detection of biomarker,
      which may open up a new way for the development of GMI-based MIA in clinical
      trials. 

PMID- 24662065
TI  - A simple procedure to synchronize concurrent measurements of gait and brain
      electrical activity and preliminary results from a pilot measurement involving
      motor-cognitive dual-tasking in healthy older and young volunteers.
AB  - BACKGROUND: The ability to record brain activity under normal walking conditions
      is the key to studying supraspinal influence on spinal gait control. NEW METHOD:
      We developed a procedure of synchronizing an electronic walkway (GAITRite, CIR
      Systems Inc.) with a multi-channel, wireless EEG-system (BrainAmp,
      Brainproducts). To assess the practicability of our procedure we performed a
      proof of concept measurement involving concurrently recording gait pattern and
      brain electrical activity in two elderly and two young participants. This
      measurement enabled us to assess the synchronization of the two data sets under
      realistic conditions. RESULTS: Only carrying a filled water glass reduced gait
      regularity in the elderly. In the young gait regularity was constant across all
      tasks. This concurs with previous findings reporting a task specific influence on
      gait. Carrying a full water glass also led to an increase in the power of the EEG
      gamma-band oscillations in frontal cortex of the elderly, but led to a decrease
      in the young participants. Carrying a full glass increased activity in frontal
      cortex of the elderly but decreased it in the young participants. COMPARISON WITH
      EXISTING METHODS: At present, concurrent recording of gait pattern and electrical
      brain activity requires participants to walk on a treadmill. Our procedure
      enables these measurements to be made under natural walking conditions. This
      allows measurements of brain activity during walking in special needs groups such
      as children, the elderly or the infirm under near natural conditions.
      CONCLUSIONS: Our procedure for synchronizing EEG and gait proved simple, reliable
      and generated data of high-quality.

PMID- 24662066
TI  - Unravelling the complex antimicrobial interactions of essential oils--the case of
      Thymus vulgaris (thyme).
AB  - Thymus vulgaris has gained tremendous popularity as an ornamental, culinary herb
      and its use in phytotherapy is well established and supported in the literature.
      The objective of this study was to explore possible interactions between selected
      molecules within Thymus vulgaris essential oil (TvEO) to gain a better
      understanding of how this complex essential oil exerts its antimicrobial
      activity. Evaluation of the antimicrobial efficacy and interactions were assessed
      on the essential oil and volatile constituents against various pathogens.
      Interactions between molecules at various ratios were graphically observed
      through the construction of isobolograms. Gas chromatography-mass spectrometry
      (GC-MS) analysis revealed 22 compounds which collectively represent >95% of the
      oil composition. Based on their minimum inhibitory concentration (MIC) values,
      they were categorised into weak (>=4 mg mL-1), moderate (2-4 mg mL-1) and
      noteworthy active (<=2 mg mL-1) compounds. For the combination study, 21%
      synergistic, 42% additive, 36% indifferent and 1% antagonistic interactions were
      observed. Most of the interactions were observed between the weak and highly
      active molecules, and interestingly, no synergistic interaction was observed
      between the highly active compounds. Synergistic and additive interactions
      between the strong and weaker antimicrobial constituents present in TvEO enhance
      the antimicrobial efficacy of this commercially important essential oil.

PMID- 24662067
TI  - Determination of pesticide residues in honeybees using modified QUEChERS sample
      work-up and liquid chromatography-tandem mass spectrometry.
AB  - Increasing emissions of chemical compounds to the environment, especially of
      pesticides, is one of factors that may explain present honeybee colony losses. In
      this work, an analytical method employing liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) was optimized for the simultaneous screening of 19
      pesticides which have not been yet determined in honeybee samples from northern
      Poland (Pomerania). The sample preparation, based on the QuEChERS method
      combining salting-out liquid-liquid extraction to acetonitrile and a dispersive
      SPE clean-up, was adjusted to honeybee samples by adding a small amount of hexane
      to eliminate beeswax. The recovery of analytes ranged from 70% to 120% with
      relative standard deviation <=20%. The limits of detection were in the range of
      0.91-25 ng/g. A total of 19 samples of honeybees from suspected pesticide
      poisoning incidents were analyzed, in which 19 different pesticides were
      determined. 

PMID- 24662068
TI  - Ginsenoside Rb1 protects rat neural progenitor cells against oxidative injury.
AB  - Ginseng, the root of Panax ginseng C.A. Meyer, has been used as a tonic to
      enhance bodily functions against various ailments for hundreds of years in Far
      Eastern countries without apparent adverse effects. Ginsenoside Rb1, one of the
      most active ingredients of ginseng, has been shown to possess various
      pharmacological activities. Here we report that Rb1 exhibits potent
      neuroprotective effects against oxidative injury induced by tert
      butylhydroperoxide (t-BHP). Lactate dehydrogenase (LDH) assay demonstrated that
      incubation with 300 um t-BHP for 2.5 h led to a significant cell loss of cultured
      rat embryonic cortex-derived neural progenitor cells (NPCs) and the cell
      viability was pronouncedly increased by 24 h pretreatment of 10 um Rb1. TUNEL
      staining further confirmed that pretreatment of Rb1 significantly reduced the
      cell apoptosis in t-BHP-induced oxidative injury. Real time PCR revealed that
      pretreatment with Rb1 activated Nrf2 pathway in cultured NPCs and led to an
      elevated expression of HO-1. The results of the present study demonstrate that
      Rb1 shows a potent anti-oxidative effect on cultured NPCs by activating Nrf2
      pathway. 

PMID- 24662069
TI  - Antioxidant activity of hispidin oligomers from medicinal fungi: a DFT study.
AB  - Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi
      Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological
      activities and strong free radical scavenging activity. To rationalize the
      antioxidant activity of a series of four hispidin oligomers and determine the
      favored mechanism involved in free radical scavenging, DFT calculations were
      carried out at the B3P86/6-31+G (d, p) level of theory in gas and solvent. The
      results showed that bond dissociation enthalpies of OH groups of hispidin
      oligomers (ArOH) and spin density delocalization of related radicals (ArO*) are
      the appropriate parameters to clarify the differences between the observed
      antioxidant activities for the four oligomers. The effect of the number of
      hydroxyl groups and presence of a catechol moiety conjugated to a double bond on
      the antioxidant activity were determined. Thermodynamic and kinetic studies
      showed that the PC-ET mechanism is the main mechanism involved in free radical
      scavenging. The spin density distribution over phenoxyl radicals allows a better
      understanding of the hispidin oligomers formation.

PMID- 24662070
TI  - Celastrol induces apoptosis in gefitinib-resistant non-small cell lung cancer
      cells via caspases-dependent pathways and Hsp90 client protein degradation.
AB  - Celastrol, a triterpene extracted from the Chinese herb Tripterygium wilfordii,
      has been shown to have multiple bioactivities. Although among these activities,
      its anti-cancer effects have attracted the most attention, the effect of
      celastrol on gefitinib-resistant non-small cell lung cancer (NSCLC) cells is not
      clearly known. Here, we examined the potency of celastrol in three different
      NSCLC cell lines. We explored its treatment mechanism in two gefitinib-resistant
      NSCLC cell lines (H1650 and H1975). Our data demonstrated that celastrol exerted
      its apoptotic effect in a dose- and time-dependent manner. Also, the mitochondria
      membrane potential was gradually lost and the ratio of Bax/Bcl-2 increased after
      the treatment of celastrol, both of which are indicators of mitochondria membrane
      integrity. Although the caspases were activated, the treatment with pan-caspase
      inhibitor could partially inhibit the level of apoptosis. Moreover, the protein
      level of Hsp90 client proteins, EGFR and AKT, was measured. Interestingly, both
      client proteins were remarkably down-regulated after the treatment of celastrol.
      Taken together, our data showed that celastrol may be developed as a promising
      agent for treating gefitinib-resistant NSCLCs by inducing apoptosis through
      caspase-dependent pathways and Hsp90 client protein degradation. 

PMID- 24662071
TI  - Structure-activity relationship study of sesquiterpene lactones and their semi
      synthetic amino derivatives as potential antitrypanosomal products.
AB  - Sesquiterpene lactones (STLs) are natural products that have potent
      antitrypanosomal activity in vitro and, in the case of cynaropicrin, also reduce
      parasitemia in the murine model of trypanosomiasis. To explore their structure
      antitrypanosomal activity relationships, a set of 34 natural and semi-synthetic
      STLs and amino-STLs was tested in vitro against T. b. rhodesiense (which causes
      East African sleeping sickness) and mammalian cancer cells (rat bone myoblast L6
      cells). It was found that the alpha-methylene-gamma-lactone moiety is necessary
      for both antitrypanosomal effects and cytotoxicity. Antitrypanosomal selectivity
      is facilitated by 2-(hydroxymethyl)acrylate or 3,4-dihydroxy-2-methylenebutylate
      side chains, and by the presence of cyclopentenone rings. Semi-synthetic STL
      amines with morpholino and dimethylamino groups showed improved in vitro activity
      over the native STLs. The dimethylamino derivative of cynaropicrin was prepared
      and tested orally in the T. b. rhodesiense acute mouse model, where it showed
      reduced toxicity over cynaropicrin, but also lost antitrypanosomal activity. 

PMID- 24662072
TI  - Design, synthesis and SAR study of novel trisubstituted pyrimidine amide
      derivatives as CCR4 antagonists.
AB  - The design, synthesis and structure-activity relationship studies of some novel
      trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are
      described. The activities of these compounds were evaluated by the CCR4-MDC
      chemotaxis inhibition assay. Compound 1, which we have previously reported as a
      potent antagonist of CCR4, was employed as the positive control. The results
      indicated that most of the synthesized compounds exhibited some chemotaxis
      inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and
      12b, with IC50 values of 0.064, 0.077 and 0.069 MUM, respectively, showed higher
      or similar activity compared with compound 1 (IC50 of 0.078 MUM). These compounds
      provide a basis for further structural modifications. The systematic structure
      activity relationship of these trisubstituted pyrimidine amide derivatives was
      discussed based on the obtained experimental data. The results from the SAR study
      may be useful for identifying more potent CCR4 antagonists.

PMID- 24662073
TI  - Protein-rich fraction of Cnidoscolus urens (L.) Arthur leaves: enzymatic
      characterization and procoagulant and fibrinogenolytic activities.
AB  - Proteolytic enzymes are important macromolecules in the regulation of biochemical
      processes in living organisms. Additionally, these versatile biomolecules have
      numerous applications in the industrial segment. In this study we have
      characterized a protein-rich fraction of Cnidoscolus urens (L.) Arthur leaves,
      rich in proteolytic enzymes, and evaluated its effects on the coagulation
      cascade. Three protein-rich fractions were obtained from the crude extract of C.
      urens leaves by precipitation with acetone. Fraction F1.0 showed higher
      proteolytic activity upon azocasein, and thus, was chosen for subsequent tests.
      The proteolytic activity of F1.0 on fibrinogen was dose-dependent and time
      dependent. The extract demonstrated procoagulant activity on citrated plasma and
      reduced the APTT, not exerting effects on PT. Despite the fibrin(ogen)olytic
      activity, F1.0 showed no defibrinogenating activity in vivo. The fraction F1.0
      did not express hemorrhagic nor hemolytic activities. The proteolytic activity
      was inhibited by E-64, EDTA and in the presence of metal ions, and increased when
      pretreated with reducing agents, suggesting that the observed activity was mostly
      due to cysteine proteases. Several bands with proteolytic activity were detected
      by zymography with gelatin, albumin and fibrinogen. The optimal enzymatic
      activity was observed in temperature of 60  degrees C and pH 5.0, demonstrating
      the presence of acidic proteases. In conclusion, these results could provide
      basis for the pharmacological application of C. urens proteases as a new source
      of bioactive molecules to treat bleeding and thrombotic disorders. 

PMID- 24662074
TI  - Structure-activity association of flavonoids in lung diseases.
AB  - Flavonoids are polyphenolic compounds classified into flavonols, flavones,
      flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to
      their chemical structures. They are abundantly found in Nature and over 8,000
      flavonoids have from different sources, mainly plant materials, have been
      described. Recently reports have shown the valuable effects of flavonoids as
      antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti
      inflammatory agents and interest in these compounds has been increasing since
      they can be helpful to human health. Several mechanisms of action are involved in
      the biological properties of flavonoids such as free radical scavenging,
      transition metal ion chelation, activation of survival genes and signaling
      pathways, regulation of mitochondrial function and modulation of inflammatory
      responses. The anti-inflammatory effects of flavonoids have been described in a
      number of studies in the literature, but not frequently associated to respiratory
      disease. Thus, this review aims to discuss the effects of different flavonoids in
      the control of lung inflammation in some disorders such as asthma, lung emphysema
      and acute respiratory distress syndrome and the possible mechanisms of action, as
      well as establish some structure-activity relationships between this biological
      potential and chemical profile of these compounds. 

PMID- 24662075
TI  - Synthesis and properties of a lacquer wax-based quarternary ammonium gemini
      surfactant.
AB  - Lacquer wax is an important fatty resource obtained from the mesocarp of the
      berries of Toxicodendron vernicifluum. In order to expand the applications of
      lacquer wax, we hydrolyzed it after establishing the best conditions for the acid
      catalyzed hydrolysis using a Box-Behnken design. Then we synthesized a
      quarternary ammonium gemini surfactant by a three-step reaction. The surface
      properties of an aqueous solution of the final product were investigated. The
      optimum conditions were 9% catalyst, 100  degrees C of reaction temperature and
      14 h of reaction time, while the maximum free fatty acids (FFA)% was 99.67%. From
      the gas chromatography, the main fatty acids of the lacquer wax were palmitic,
      oleic and octadecanoic acid. The lacquer wax gemini surfactant was synthesized,
      and its structure was confirmed by IR and NMR. The experiments showed that the
      critical micelle concentration (CMC) is 5 * 10-4 mol.L-1, the surface tension is
      33.6 mN.m-1. When the content of surfactant was 0.1%, the separation time of 5 mL
      water was 10 min.

PMID- 24662076
TI  - Antimicrobial activities against periodontopathic bacteria of Pittosporum tobira
      and its active compound.
AB  - The study of medicinal plants for treatment of periodontitis is of great value to
      establish their efficacy as sources of new antimicrobial drugs. Five hundred and
      fifty eight Korean local plant extracts were screened for antibacterial activity
      against representative periodontopathic bacteria such as Porphyromonas
      gingivalis, Prevotella intermedia, and Fusobacterium nucleatum. Among the various
      medicinal plants, the alcohol extract of Pittosporum tobira, which significantly
      exhibited antibacterial effect for all tested strains, showed the highest
      activity in the antimicrobial assays. NMR analyses revealed that R1-barrigenol, a
      triterpene sapogenin, was the most effective compound in P. tobira. These results
      demonstrated that P. tobira possesses antimicrobial properties and would be
      beneficial for the prevention and treatment of periodontitis. 

PMID- 24662077
TI  - Trigocherrierin A, a potent inhibitor of chikungunya virus replication.
AB  - Trigocherrierin A (1) and trigocherriolide E (2), two new daphnane diterpenoid
      orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and
      trigocherriolides A-C, were isolated from the leaves of Trigonostemon cherrieri.
      Their structures were identified by mass spectrometry, extensive one- and two
      dimensional NMR spectroscopy and through comparison with data reported in the
      literature. These compounds are potent and selective inhibitors of chikungunya
      virus (CHIKV) replication. Among the DDOs isolated, compound 1 exhibited the
      strongest anti-CHIKV activity (EC50 = 0.6 +/- 0.1 uM, SI = 71.7).

PMID- 24662078
TI  - Entrapment of probiotics in water extractable arabinoxylan gels: rheological and
      microstructural characterization.
AB  - Due to their porous structure, aqueous environment and dietary fiber nature
      arabinoxylan (AX) gels could have potential applications for colon-specific
      therapeutic molecule delivery. In addition, prebiotic and health related effects
      of AX have been previously demonstrated. It has been also reported that cross
      linked AX can be degraded by bacteria from the intestinal microbiota. However, AX
      gels have not been abundantly studied as carrier systems and there is no
      information available concerning their capability to entrap cells. In this
      regard, probiotic bacteria such as Bifidobacterium longum have been the focus of
      intense research activity lately. The objective of this research was to
      investigate the entrapment of probiotic B. longum in AX gels. AX solution at 2%
      (w/v) containing B. longum (1 * 107 CFU/cm) formed gels induced by laccase as
      cross-linking agent. The entrapment of B. longum decreased gel elasticity from 31
      to 23 Pa, probably by affecting the physical interactions taking place between
      WEAX chains. Images of AX gels containing B. longum viewed under a scanning
      electron microscope show the gel network with the bacterial cells entrapped
      inside. The microstructure of these gels resembles that of an imperfect
      honeycomb. The results suggest that AX gels can be potential candidates for the
      entrapment of probiotics.

PMID- 24662079
TI  - Synthesis of new 1,2,3-triazol-4-yl-quinazoline nucleoside and acyclonucleoside
      analogues.
AB  - In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo
      quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar
      cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido
      2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave
      conditions. None of the compounds selected showed significant anti-HCV activity
      in vitro. 

PMID- 24662080
TI  - Artichoke, cynarin and cyanidin downregulate the expression of inducible nitric
      oxide synthase in human coronary smooth muscle cells.
AB  - Artichoke (Cynara scolymus L.) is one of the world's oldest medicinal plants with
      multiple health benefits. We have previously shown that artichoke leaf extracts
      and artichoke flavonoids upregulate the gene expression of endothelial-type
      nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by
      the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a
      pro-inflammatory role in the vasculature. The present study was aimed to
      investigate the effects of artichoke on iNOS expression in human coronary artery
      smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to
      an induction of iNOS mRNA expression. This iNOS induction was concentration- and
      time-dependently inhibited by an artichoke leaf extract (1-100 ug/mL, 6 h or 24
      h). Consistently, the artichoke leaf extract also reduced cytokine-induced iNOS
      promoter activation and iNOS protein expression. In addition, treatment of HCASMC
      with four well-known artichoke compounds (cynarin > cyanidin > luteolin ~
      cynaroside) led to a downregulation iNOS mRNA and protein expression, with
      cynarin being the most potent one. In conclusion, artichoke contains both eNOS
      upregulating and iNOS-downregulating compounds. Such compounds may contribute to
      the beneficial effects of artichoke and may per se have therapeutic potentials. 

PMID- 24662081
TI  - Additional new minor cucurbitane glycosides from Siraitia grosvenorii.
AB  - Continuous phytochemical studies of the crude extract of Luo Han Guo (Siraitia
      grosvenorii) furnished three additional new cucurbitane triterpene glycosides,
      namely 11-deoxymogroside V, 11-deoxyisomogroside V, and 11-deoxymogroside VI. The
      structures of all the isolated compounds were characterized on the basis of
      extensive NMR and mass spectral data as well as hydrolysis studies. The complete
      1H- and 13C-NMR spectral assignments of the three unknown compounds are reported
      for the first time based on COSY, TOCSY, HSQC, and HMBC spectroscopic data.

PMID- 24662082
TI  - Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes,
      modulating steroid hormone levels in H295R cells.
AB  - Major rooibos flavonoids--dihydrochalcones, aspalathin and nothofagin, flavones-
      orientin and vitexin, and a flavonol, rutin, were investigated to determine their
      influence on the activity of adrenal steroidogenic enzymes, 3beta-hydroxysteroid
      dehydrogenase (3betaHSD2) and cytochrome P450 (P450) enzymes, P450 17alpha
      hydroxylase/17,20-lyase (CYP17A1), P450 21-hydroxylase (CYP21A2) and P450 11beta
      hydroxylase (CYP11B1). All the flavonoids inhibited 3betaHSD2 and CYP17A1
      significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1,
      was both substrate and flavonoid specific. The dihydrochalcones inhibited the
      activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and
      vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition
      of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit
      CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos
      inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of
      other enzyme activities was <20%. In H295R cells, rutin had the greatest
      inhibitory effect on steroid production upon forskolin stimulation, reducing
      total steroid output 2.3-fold, while no effect was detected under basal
      conditions. Nothofagin and vitexin had a greater inhibitory effect on overall
      steroid production compared to aspalathin and orientin, respectively. The latter
      compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin
      contain a single hydroxyl group. In addition, all of the flavonoids are
      glycosylated, albeit at different positions--dihydrochalcones at C3' and flavones
      at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on
      ring C. Structural differences regarding the number and position of hydroxyl and
      glucose moieties as well as structural flexibility could indicate different
      mechanisms by which these flavonoids influence the activity of adrenal
      steroidogenic enzymes.

PMID- 24662083
TI  - Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds
      against bacterial adhesion of Helicobacter pylori.
AB  - Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for
      treatment of gastritis based on seed polysaccharides that inhibit the adhesion of
      Helicobacter pylori to stomach cells. For detailed investigations an
      arabinogalactan protein (F2) was isolated from seeds and characterized concerning
      molecular weight, carbohydrate, amino acid composition, linkage, configuration
      and reaction with beta-glucosyl Yariv. Functional testing of F2 was performed by
      semiquantitative in situ adhesion assay on sections of human gastric mucosa and
      by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and
      human stomach AGS cells. Bacterial adhesins affected were identified by overlay
      assay with immobilized ligands. 125I-radiolabeled F2 served for binding studies
      to H. pylori and interaction experiments with BabA and SabA. F2 had no cytotoxic
      effects against H. pylori and AGS cells; but inhibited bacterial binding to human
      gastric cells. F2 inhibited the binding of BabA and fibronectin-binding adhesin
      to its specific ligands. Radiolabeled F2 bound non-specifically to different
      strains of H. pylori; and to BabA deficient mutant. F2 did not lead to subsequent
      feedback regulation or increased expression of adhesins or virulence factors.
      From these data the non-specific interactions between F2 and the H. pylori lead
      to moderate antiadhesive effects.

PMID- 24662084
TI  - Discrimination of Dendrobium officinale and its common adulterants by combination
      of normal light and fluorescence microscopy.
AB  - The stems of Dendrobium officinale Kimura et Migo, named Tie-pi-shi-hu, is one of
      the most endangered and precious species in China. Because of its various
      pharmacodynamic effects, D. officinale is widely recognized as a high-quality
      health food in China and other countries in south and south-east Asia. With the
      rising interest of D. officinale, its products have a high price due to a limited
      supply. This high price has led to the proliferation of adulterants in the
      market. To ensure the safe use of D. officinale, a fast and convenient method
      combining normal and fluorescence microscopy was applied in the present study to
      distinguish D. officinale from three commonly used adulterants including Zi-pi
      shi-hu (D. devonianum), Shui-cao-shi-hu (D. aphyllum), Guang-jie-shi-hu (D.
      gratiosissimum). The result demonstrated that D. officinale could be identified
      by the characteristic "two hat-shaped" vascular bundle sheath observed under the
      fluorescence microscopy and the distribution of raphides under normal light
      microscopy. The other three adulterants could be discriminated by the vascular
      bundle differences and the distribution of raphides under normal light
      microscopy. This work indicated that combination of normal light and fluorescence
      microscopy is a fast and efficient technique to scientifically distinguish D.
      officinale from the commonly confused species. 

PMID- 24662085
TI  - Microencapsulation of purified amylase enzyme from pitaya (Hylocereus polyrhizus)
      peel in Arabic gum-chitosan using freeze drying.
AB  - Amylase is one of the most important enzymes in the world due to its wide
      application in various industries and biotechnological processes. In this study,
      amylase enzyme from Hylocereus polyrhizus was encapsulated for the first time in
      an Arabic gum-chitosan matrix using freeze drying. The encapsulated amylase
      retained complete biocatalytic activity and exhibited a shift in the optimum
      temperature and considerable increase in the pH and temperature stabilities
      compared to the free enzyme. Encapsulation of the enzyme protected the activity
      in the presence of ionic and non-ionic surfactants and oxidizing agents (H2O2)
      and enhanced the shelf life. The storage stability of amylase is found to
      markedly increase after immobilization and the freeze dried amylase exhibited
      maximum encapsulation efficiency value (96.2%) after the encapsulation process.
      Therefore, the present study demonstrated that the encapsulation of the enzyme in
      a coating agent using freeze drying is an efficient method to keep the enzyme
      active and stable until required in industry.

PMID- 24662086
TI  - Atomic model and micelle dynamics of QS-21 saponin.
AB  - QS-21 is a saponin extracted from Quillaja saponaria, widely investigated as a
      vaccine immunoadjuvant. However, QS-21 use is mainly limited by its chemical
      instability, significant variety in molecular composition and low tolerance dose
      in mammals. Also, this compound tends to form micelles in a concentration
      dependent manner. Here, we aimed to characterize its conformation and the process
      of micelle formation, both experimentally and computationally. Therefore,
      molecular dynamics (MD) simulations were performed in systems containing
      different numbers of QS-21 molecules in aqueous solution, in order to evaluate
      the spontaneous micelle formation. The applied methodology allowed the generation
      of micelles whose sizes were shown to be in high agreement with small-angle X-ray
      scattering (SAXS). Furthermore, the ester linkage between fucose and acyl chain
      was less solvated in the micellar form, suggesting a reduction in hydrolysis.
      This is the first atomistic interpretation of previous experimental data, the
      first micellar characterization of saponin micelles by SAXS and first
      tridimensional model of a micelle constituted of saponins, contributing to the
      understanding of the molecular basis of these compounds. 

PMID- 24662087
TI  - Synthesis and biological activity of some bile acid-based camptothecin analogues.
AB  - In an effort to decrease the toxicity of camptothecin (CPT) and improve
      selectivity for hepatoma and colon cancer cells, bile acid groups were introduced
      into the CPT 20 or 10 positions, resulting in the preparation of sixteen novel
      CPT-bile acid analogues. The compounds in which a bile acid group was introduced
      at the 20-hydroxyl group of CPT showed better cytotoxic selectivity for human
      hepatoma and colon cancer cells than for human breast cancer cells. Fluorescence
      microscopy analysis demonstrated that one compound (E2) entered human hepatoma
      cells more effectively than it did human breast cancer cells. Compound G4
      exhibited the best anti-tumour activity in vivo. These results suggested that
      introduction of a bile acid group at the 20-position of CPT could decrease
      toxicity in vivo and improve selectivity for hepatoma cells. 

PMID- 24662088
TI  - Synthesis, cytotoxic activity and 2D-QSAR study of some imidazoquinazoline
      derivatives.
AB  - A novel series of 4-substituted amino-7,8-dimethoxy-1-phenylimidazo[1,5
      a]quinazolin-5(4H)-one derivatives was designed, synthesized and tested for their
      antitumor activity against a human mammary carcinoma cell line (MCF7). Compound
      5a was found to be the most active derivative. Physico-chemical parameters were
      also determined and revealed that most of the compounds obeyed the "rule of five"
      properties with good absorption percentages. 2D-QSAR studies revealed a well
      predictive and statistically significant and cross validated QSAR model that
      helps to explore some expectedly potent compounds. 

PMID- 24662090
TI  - Synthesis of All-Z-1,6,9,12,15-octadecapenten-3-one, a vinyl ketone
      polyunsaturated marine natural product isolated from Callysponga sp.
AB  - The synthesis of the marine natural product 1,6Z,9Z,12Z,15Z-octadecapentaen-3-one
      (1) has been achieved by two different routes starting from the ethyl esters of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Using
      EPA ethyl ester as starting material the polyunsaturated vinyl ketone lipid 1 was
      obtained in 17% overall yield. 

PMID- 24662089
TI  - Antischistosomal activity of the terpene nerolidol.
AB  - Schistosomiasis is a neglected tropical disease that affects hundreds of millions
      of people worldwide. Since the treatment of this disease currently relies on a
      single drug, praziquantel, new and safe schistosomicidal agents are urgently
      required. Nerolidol, a sesquiterpene present in the essential oils of several
      plants, is found in many foods and was approved by the U.S. Food and Drug
      Administration. In this study we analysed the in vitro antiparasitic effect of
      nerolidol on Schistosoma mansoni adult worms. Nerolidol at concentrations of 31.2
      and 62.5 MUM reduced the worm motor activity and caused the death of all male and
      female schistosomes, respectively. In addition, confocal laser scanning
      microscopy revealed morphological alterations on the tegument of worms such as
      disintegration, sloughing and erosion of the surface, and a correlation between
      viability and tegumental damage was observed. In conclusion, nerolidol may be a
      promising lead compound for the development of antischistosomal natural agents. 

PMID- 24662092
TI  - Goat milk fat naturally enriched with conjugated linoleic acid increased
      lipoproteins and reduced triacylglycerol in rats.
AB  - Goat milk is source of different lipids, including conjugated linoleic acid
      (CLA). CLA reduces body fat and protect against cardiovascular diseases. In the
      present study fat from goat milk naturally enriched with CLA was used. Male
      Wistar rats were divided into three groups that received during a 10 week diet
      with different lipid sources: soybean oil (CON), coconut oil (CO) and goat milk
      fat naturally enriched with CLA (GM-CLA). We evaluated the effects of a GM-CLA on
      biochemistry parameters--high density lipoprotein (HDL), triacylglycerol (TAG),
      TAG/HDL ratio, total cholesterol and glucose, body weight and histopathological
      aspects of the intestine and liver. GM-CLA increased body weight from the second
      to the fifth week of the experiment compared to CON. Feed intake differed between
      the CON group and GM-CLA early in the first to third week of the experiments and
      later between the ninth and tenth week. The CLA-diet group showed increased
      levels of HDL, reduced levels of TAG and TAG/HDL ratio and no effect on LDL, but
      enhanced total cholesterol. Serum glucose of the GM-CLA group showed no
      difference from the control group. Thus, a GM-CLA diet promoted growth in young
      rats and acted as protector of cardiovascular function, but further studies are
      still needed to clarify these effects.

PMID- 24662091
TI  - Isolation and characterization of microsatellite markers for Cotinus coggygria
      Scop. (Anacardiaceae) by 454 pyrosequencing.
AB  - Cotinus coggygria Scop. (Anacardiaceae) is a deciduous shrub or small tree that
      is native to a large area covering from southern Europe, east across central
      Asia, and the Himalayas in northern China. Shotgun 454 pyrosequencing was used to
      develop microsatellite markers from the genome of C. coggygria. In this study,
      349 microsatellite loci were identified from 40,074 individual sequence reads
      produced by one-sixteenth run, and primer pairs were designed for these loci. To
      test the primer amplification efficiency, 50 microsatellite primer pairs were
      tested across 12 individuals from two C. coggygria populations (Wuzhi Mountain:
      36 degrees 30'N, 113 degrees 39'E; Tianlong Mountain: 37 degrees 42'N, 112
      degrees 26'E). Among the 50 tested primer pairs, eight were found to be
      polymorphic. The average allele number of the microsatellites was 3.5 per locus,
      with a range from two to five. The inbreeding coefficient ranged from -0.478 to
      0.222. The observed and expected heterozygosities varied from 0.167 to 0.750 and
      from 0.163 to 0.743, respectively. This set of markers is potentially useful for
      assessing the genetic diversity, as well as for understanding the population
      structure and phylogeographical and landscape genetic patterns, of C. coggygria. 

PMID- 24662093
TI  - Platinum(II) oxalato complexes involving adenosine-based N-donor ligands:
      synthesis, characterization and cytotoxicity evaluation.
AB  - A one-step synthetic procedure using the reaction of potassium
      bis(oxalato)platinate(II) with the corresponding N6-benzyladenosine derivative
      (nL) provided the [Pt(ox)(nL)2]?1.5H2O oxalato (ox) complexes 1-5, involving the
      nL molecules as monodentate coordinated N-donor ligands. The complexes were
      thoroughly characterized by elemental analysis, multinuclear (1H, 13C, 15N,
      1195Pt) and two dimensional NMR, infrared and Raman spectroscopy, and mass
      spectrometry, proving their composition and purity as well as coordination of nL
      through the N7 atom of the purine moiety. Geometry of [Pt(ox)(4FL)2] (5) was
      optimized at the B3LYP/LANLTZ/6-311G** level of theory. The complexes were
      screened for their in vitro cytotoxicity against two human cancer cell lines (HOS
      osteosarcoma and MCF7 breast adenocarcinoma), but they did not show any effect up
      to the concentration of 50.0 uM (compounds 1, 2) or 20.0 uM (compounds 3-5).

PMID- 24662095
TI  - Model-driven experimental evaluation of struvite nucleation, growth and
      aggregation kinetics.
AB  - Nutrient stewardship is emerging as an issue of global importance, which will
      drive the development of nutrient recovery in the near to medium future. This
      will impact wastewater treatment practices, environmental protection, sustainable
      agriculture and global food security. A modelling framework for precipitation
      based nutrient recovery systems has been developed, incorporating non-ideal
      solution thermodynamics, a dynamic mass balance and a dynamic population balance
      to track the development of the precipitating particles. The mechanisms of
      crystal nucleation and growth and, importantly, aggregation are considered. A
      novel approach to the population balance embeds the nucleation rate into the
      model, enabling direct regression of its kinetic parameters. The case study
      chosen for the modelling framework is that of struvite precipitation, given its
      wide interest and commercial promise as one possible nutrient recovery pathway.
      Power law kinetic parameters for nucleation, crystal growth and particle
      aggregation rates were regressed from an ensemble data set generated from 14
      laboratory seeded batch experiments using synthetic solutions. These experiments
      were highly repeatable, giving confidence to the regressed parameter values. The
      model successfully describes the dynamic responses of solution pH, the evolving
      particle size distribution subject to nucleation, growth and aggregation effects
      and the aqueous magnesium concentration in the liquid phase. The proposed
      modelling framework could well be extended to other, more complex systems,
      leading to an improved understanding and commensurately greater confidence in the
      design, operation and optimisation of large-scale nutrient recovery processes
      from complex effluents. 

PMID- 24662096
TI  - Monte Carlo comparison of superficial dose between flattening filter free and
      flattened beams.
AB  - This study investigates the superficial dose from FFF beams in comparison with
      the conventional flattened ones using a Monte Carlo (MC) method. Published phase
      space files which incorporated real geometry of a TrueBeam accelerator were used
      for the dose calculation in phantom and clinical cases. The photon fluence on the
      central axis is 3 times that of a flattened beam for a 6 MV FFF beam and 5 times
      for a 10 MV beam. The mean energy across the field in air at the phantom surface
      is 0.92-0.95 MeV for the 6 MV FFF beam and 1.18-1.30 MeV for the corresponding
      flattened beam. At 10 MV, the values are 1.52-1.72 and 2.15-2.87 MeV for the FFF
      and flattened beams, respectively. The phantom dose at the depth of 1 mm in the 6
      MV FFF beam is 6% +/- 2.5% (of the maximum dose) higher compared to the flattened
      beam for a 25 * 25 cm(2) field and 14.6% +/- 1.9% for the 2 * 2 cm(2) field. For
      the 10 MV beam, the corresponding differences are 3.4% +/- 1.5% and 10.7% +/-
      0.6%. The skin dose difference at selected points on the patient's surface
      between the plans using FFF and flattened beams in the head-and-neck case was
      6.5% +/- 2.3% (1SD), and for the breast case it was 6.4% +/- 2.3%. The Monte
      Carlo simulations showed that due to the lower mean energy in the FFF beam, the
      clinical superficial dose is higher without the flattening filter compared to the
      flattened beam. 

PMID- 24662097
TI  - Image quality assessment of an iterative reconstruction algorithm applied to
      abdominal CT imaging.
AB  - PURPOSE: To compare the noise and accuracy on images of the whole porcine liver
      acquired with iterative reconstruction (IMR, Philips Healthcare, Cleveland, OH,
      USA) and filtered back projection (FBP) methods. MATERIALS AND METHODS: We used
      non-enhanced porcine liver to simulate the human liver and acquired it 100 times
      to obtain the average FBP value as the ground-truth. The mean and the standard
      deviation ("inter-scan SD") of the pixel values on the 100 image acquisitions
      were calculated for FBP and for three levels of IMR (L1, L2, and L3). We also
      calculated the noise power spectrum (NPS) and the normalized NPS for the 100
      image acquisitions. RESULTS: The spatial SD for the porcine liver parenchyma on
      these slices was 9.92, 4.37, 3.63, and 2.30 Hounsfield units with FBP, IMR-L1,
      IMR-L2, and IMR-L3, respectively. The detectability of small faint features was
      better on single IMR than single FBP images. The inter-scan SD value for IMR-L3
      images was 53% larger at the liver edges than at the liver parenchyma; it was
      only 10% larger on FBP images. Assessment of the normalized NPS showed that the
      noise on IMR images was comprised primarily of low-frequency components.
      CONCLUSION: IMR images yield the same structure informations as FBP images and
      image accuracy is maintained. On level 3 IMR images the image noise is more
      strongly suppressed than on IMR images of the other levels and on FBP images.

PMID- 24662099
TI  - Pharmacological modulation of GSAP reduces amyloid-beta levels and tau
      phosphorylation in a mouse model of Alzheimer's disease with plaques and tangles.
AB  - Accumulation of neurotoxic amyloid-beta (Abeta) is a major hallmark of
      Alzheimer's disease (AD) pathology and an important player in its clinical
      manifestations. Formation of Abeta is controlled by the availability of an enzyme
      called gamma-secretase. Despite its blockers being attractive therapeutic tools
      for lowering Abeta, this approach has failed because of their serious toxic side
      effects. The discovery of the gamma-secretase activating protein (GSAP), a co
      factor for this protease which facilitates Abeta production without affecting
      other pathways responsible for the toxicity, is giving us the opportunity to
      develop a safer anti-Abeta therapy. In this study we have characterized the
      effect of Imatinib, an inhibitor of GSAP, in the 3*Tg mice, a mouse model of AD
      with plaques and tangles. Compared with controls, mice receiving the drug had a
      significant reduction in brain Abeta levels and deposition, but no changes in the
      steady state levels of AbetaPP, BACE-1, ADAM-10, or the four components of the
      gamma-secretase complex. By contrast, Imatinib-treated animals had a significant
      increase in CTF-beta and a significant reduction in GSAP expression levels.
      Additionally, we observed that tau phosphorylation was reduced at specific
      epitopes together with its insoluble fraction. In vitro studies confirmed that
      Imatinib prevents Abeta formation by modulating gamma-secretase activity and GSAP
      levels. Our findings represent the first in vivo demonstration of the biological
      role that GSAP plays in the development of the AD-like neuropathologies. They
      establish this protein as a viable target for a safer anti-Abeta therapeutic
      approach in AD. 

PMID- 24662100
TI  - Verbal repetition in primary progressive aphasia and Alzheimer's disease.
AB  - We aimed to explore the nature of verbal repetition deficits and infer the
      cognitive systems involved in primary progressive aphasia (PPA) and Alzheimer's
      disease (AD). A total of 63 patients (13 semantic variant (sv-PPA), 17
      nonfluent/agrammatic variant (nfv-PPA), 10 logopenic variant (lv-PPA), 23 AD) and
      13 matched healthy controls completed a battery of tests that included naming,
      word comprehension, digit span, repetition of multisyllabic single words,
      monosyllabic word span presented under similar and dissimilar phonological
      conditions, and sentence repetition. All patient groups displayed some level of
      impairment, however, specific patterns emerged in each variant. Participants with
      sv-PPA were the least impaired, showing marginal difficulties exclusively for
      sentence repetition, whereas those with lv-PPA had the worst overall performance.
      Cases with nfv-PPA showed compromised repetition of multisyllabic and
      phonologically similar words. The deficit in cases with AD was confined to span
      tasks. These distinctive patterns of language impairments can assist in the
      differential diagnosis of PPA variants and point toward the vulnerability of
      specific cognitive systems in each syndrome. 

PMID- 24662098
TI  - Discordance between changes in the gut microbiota and pathogenicity in a mouse
      model of spontaneous colitis.
AB  - Under conventional conditions, mice deficient in core 1-derived O-glycans (TM-IEC
      C1galt1(-/-)), which have a defective mucus layer, experienced spontaneous
      inflammation of the colon. Analysis of fecal bacterial populations by
      pyrosequencing of 16S rRNA gene showed that disease in conventional TM-IEC
      C1galt1(-/-) was associated with shifts in the microbiota manifested by increases
      in Lactobacillus and Clostridium species, and decreases in unclassified
      Ruminococcaceae and Lachnospiraceae. Under germ-free (GF) conditions, TM-IEC
      C1galt1(-/-) presented decreased goblet cells, but did not develop inflammation.
      Monoassociation of GF TM-IEC C1galt1(-/-) revealed that bacterial species differ
      significantly in their ability to induce inflammatory changes. Bacteroides
      thetaiotaomicron caused inflammation, while Lactobacillus johnsonii (enriched
      during colitis) did not. These observations demonstrate that not all microbiota
      shifts that correlate with disease contribute to pathogenesis. 

PMID- 24662101
TI  - Robust gene dysregulation in Alzheimer's disease brains.
AB  - The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing
      disease mechanism at the gene expression level. However, thousands of genes have
      been reported to be dysregulated in AD brains in existing studies, and the
      consistency or discrepancy among these studies has not been thoroughly examined.
      Toward this end, we conducted a comprehensive survey of the brain transcriptome
      datasets for AD and other neurological diseases. We first demonstrated that the
      frequency of observed dysregulation in AD was highly correlated with the
      reproducibility of the dysregulation. Based on this observation, we selected 100
      genes with the highest frequency of dysregulation to illustrate the core
      perturbation in AD brains. The dysregulation of these genes was validated in
      several independent datasets for AD. We further identified 12 genes with strong
      correlation of gene expression with disease progression. The relevance of these
      genes to disease progression was also validated in an independent dataset.
      Interestingly, we found a transcriptional "cushion" for these 100 genes in the
      less vulnerable visual cortex region, which may be a critical component of the
      protection mechanism for less vulnerable brain regions. To facilitate the
      research in this field, we have provided the expression information of ~8000
      relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn).

PMID- 24662102
TI  - Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for
      the treatment of Alzheimer's disease: a systematic review and meta-analysis.
AB  - BACKGROUND: The role of currently available drugs for Alzheimer's disease (AD)
      has been controversial, with some national formularies restricting their use, and
      health economists questioning whether the small clinical effects are economically
      worthwhile. OBJECTIVE: To estimate the efficacy and safety of donepezil,
      galantamine, rivastigmine, and memantine for the treatment of AD. METHODS: Double
      blind, placebo-controlled, with random assignment to a cholinesterase inhibitor
      or memantine trials were included into the pooled studies. RESULTS: Cognitive
      effects were significant for all drugs, ranging from a -1.29 points mean
      difference (95% CI -2.30 to -0.28) in the 20 mg daily memantine trials to -3.20
      points (95% CI -3.28 to -3.12) in the 32 mg daily galantamine group. Only
      memantine had no effect on the Clinicians' Global Impression of Change scale. No
      behavioral benefits were observed, except for -2.72 (95% CI -4.92 to -0.52) in
      the 10 mg daily donepezil group and -1.72 (95% CI -3.12 to -0.33) for 24 mg daily
      galantamine trial. Only 5 mg daily donepezil had no effect on the function
      outcome. Compared with placebo, more dropouts and adverse events occurred with
      the cholinesterase inhibitors, but not with memantine. CONCLUSIONS:
      Cholinesterase inhibitors and memantine are able to stabilize or slow decline in
      cognition, function, behavior, and global change.

PMID- 24662103
TI  - Statins and vascular dementia: a review.
AB  - The impact of statin therapy on dementia has been a hot topic of debate over the
      last decade and still remains highly controversial. Among all causes of dementia,
      vascular dementia (VaD) is the one type that is more likely to benefit from
      statins. To date no randomized clinical trials have been published and no
      systematic review has investigated a possible preventive effect of statins on the
      VaD subtype. In the present literature review, we tried to identify all available
      data on the effect of statins specifically in patients with VaD, and to further
      discuss this possible association. Our literature search highlighted two cross
      sectional studies, two prospective cohort studies, and one retrospective cohort
      study. Two of the studies found a significant positive effect of statin treatment
      on VaD, depicted by the lower incidence of VaD in statin users, while the others
      reported non-significant associations. The relatively small numbers of VaD
      patients and statin users, as well as the presence of confounders and biases,
      make the interpretation of results extremely difficult. Statins may exert a
      benefit in the prevention of all-type dementia and VaD, through several
      mechanisms except for hyperlipidemia reduction. A well-designed randomized
      clinical trial is the ideal study design to address the effect of statin therapy
      in VaD and to draw final conclusions. 

PMID- 24662104
TI  - Update on Susac syndrome: new insights in brain and retinal imaging and treatment
      options.
AB  - Susac syndrome (SuS) is a rare endotheliopathy of the brain, the retina, and the
      inner ear. The underlying pathophysiology is likely an autoimmune mediated
      occlusion of microvessels resulting in variable degrees of central nervous system
      (CNS) dysfunction, visual disturbances, and hearing loss. The disease manifests
      either with a monophasic or polycyclic course. Patients suffering from SuS are
      frequently misdiagnosed as having inflammatory demyelinating CNS disease,
      particularly multiple sclerosis because of some overlap in the clinical
      presentation and the paraclinical findings. Since appropriate treatment of SuS is
      crucial for the prognosis, a timely and sound establishment of the diagnosis is
      important. Here, we summarize currently available information on the clinical
      presentation and diagnostic procedures in SuS. In particular, we discuss the
      added value of advanced techniques of brain and retinal imaging such as ultrahigh
      field magnetic resonance imaging and optical coherence tomography in SuS with
      respect to its differential diagnosis and pathophysiology. Since evidence-based
      treatment standards will not be available in the near future, we share some
      experiences in terms of treatment options. Finally, we briefly outline future
      areas of research in SuS. 

PMID- 24662105
TI  - Post-translational modifications in Alzheimer's disease and the potential for new
      biomarkers.
AB  - The ability to detect and diagnose Alzheimer's disease (AD) early is an ever
      pressing issue, and the development of markers of disease progression that are
      able to distinguish AD patients from normal aging and patients with alternative
      forms of dementia, is at the center of the issue. Protein markers of disease, or
      biomarkers, can be used not only to monitor the progression of AD, but also allow
      identification of patients suitable for potential therapy, and the response to
      therapy to be monitored. Cerebrospinal fluid protein biomarkers are important in
      this early AD diagnosis, and three such biomarkers have been extensively studied
      and are reviewed here. In addition, post translational protein modifications of
      proteins important in AD pathology are also discussed. If additional biomarkers
      can be identified and thoroughly understood, potential therapeutic agents can be
      better designed, and the effects of therapeutic intervention on disease
      progression can be monitored. 

PMID- 24662106
TI  - European Society for Paediatric Endocrinology consensus guidelines on screening,
      diagnosis, and management of congenital hypothyroidism.
AB  - OBJECTIVE: The aim was to formulate practice guidelines for the diagnosis and
      management of congenital hypothyroidism (CH). EVIDENCE: A systematic literature
      search was conducted to identify key articles relating to the screening,
      diagnosis, and management of CH. The evidence-based guidelines were developed
      with the Grading of Recommendations, Assessment, Development and Evaluation
      (GRADE) system, describing both the strength of recommendations and the quality
      of evidence. In the absence of sufficient evidence, conclusions were based on
      expert opinion. CONSENSUS PROCESS: Thirty-two participants drawn from the
      European Society for Paediatric Endocrinology and five other major scientific
      societies in the field of pediatric endocrinology were allocated to working
      groups with assigned topics and specific questions. Each group searched the
      literature, evaluated the evidence, and developed a draft document. These papers
      were debated and finalized by each group before presentation to the full assembly
      for further discussion and agreement. RECOMMENDATIONS: The recommendations
      include: worldwide neonatal screening, approaches to assess the cause (including
      genotyping) and the severity of the disorder, the immediate initiation of
      appropriate L-T4 supplementation and frequent monitoring to ensure dose
      adjustments to keep thyroid hormone levels in the target ranges, a trial of
      treatment in patients suspected of transient CH, regular assessments of
      developmental and neurosensory functions, consulting health professionals as
      appropriate, and education about CH. The harmonization of diagnosis, management,
      and routine health surveillance would not only optimize patient outcomes, but
      should also facilitate epidemiological studies of the disorder. Individuals with
      CH require monitoring throughout their lives, particularly during early childhood
      and pregnancy.

PMID- 24662107
TI  - Severe cutaneous adverse reactions to drugs: from patients to the national office
      for compensation of medical accidents.
AB  - BACKGROUND: Administrative bodies for compensating medical accidents were created
      in France in 2002. OBJECTIVES: To evaluate the knowledge patients with severe
      cutaneous adverse reactions (SCARs) have of procedures and to compare the rate of
      compensation for SCARs for France and for our referral center. METHODS: A
      questionnaire was sent to 247 patients of our SCARs referral center and 225
      patients with Stevens-Johnson syndrome and toxic epidermal necrolysis from the
      patient association AMALYSTE. We calculated the rate of compensation for France
      and our center. RESULTS: Among the 123 respondents (26%), 28 (23%) knew the
      compensation procedure; 13 (11%) had received compensation. The Commission of
      Conciliation and Compensation had received 63 applications for SCARs since 2002
      and proposed compensation for 56%. The estimated rate of compensation for France
      was 2.6% and 2.5% for our referral center (p = 0.9). CONCLUSIONS: The procedure
      of compensation for SCARs is misunderstood. Better information should be
      disseminated for patients with threshold disability conditions.

PMID- 24662108
TI  - Effect of TiO2 addition on surface microstructure and bioactivity of fluorapatite
      coatings deposited using Nd:YAG laser.
AB  - To study the effect of titania (TiO2) addition on the surface microstructure and
      bioactivity of fluorapatite coatings, fluorapatite was mixed with TiO2 in 1:0.5
      (FA + 0.5TiO2), 1:0.8 (FA + 0.8TiO2), and 1:1 (FA + TiO2) ratios (wt%) and clad
      on Ti-6Al-4V substrates using an Nd:YAG laser system. The experimental results
      show that the penetration depth of the weld decreases with increasing TiO2
      content. Moreover, the subgrain structure of the coating layer changes from a
      fine cellular-like structure to a cellular-dendrite-like structure as the amount
      of TiO2 increases. Consequently, as the proportion of TiO2 decreases (increase in
      fluorapatite content), the Ca/P ratio of the coating layer also decreases. The
      immersion of specimens into simulated body fluid resulted in the formation of
      individual apatite. With a lower Ca/P ratio before immersion, the growth of the
      apatite was faster and then the coating layer provided a better bioactivity. X
      ray diffraction analysis results show that prior to simulated body fluid
      immersion, the coating layer in all three specimens was composed mainly of
      fluorapatite, CaTiO3, and Al2O3 phases. Following simulated body fluid immersion,
      a peak corresponding to hydroxycarbonated apatite appeared after 2 days in the FA
      + 0.5TiO2 and FA + 0.8TiO2 specimens and after 7 days in the FA + TiO2 specimen.
      Overall, the results show that although the bioactivity of the coating layer
      tended to decrease with increasing TiO2 content, in accordance with the above
      mentioned ratios, the bioactivity of all three specimens remained generally good.

PMID- 24662109
TI  - Powdered ZELIAC augmented sequencing batch reactors (SBR) process for co
      treatment of landfill leachate and domestic wastewater.
AB  - Sequencing batch reactor (SBR) is one of the various methods of biological
      treatments used for treating wastewater and landfill leachate. This study
      investigated the treatment of landfill leachate and domestic wastewater by adding
      a new adsorbent (powdered ZELIAC; PZ) to the SBR technique. ZELIAC consists of
      zeolite, activated carbon, lime stone, rice husk ash, and Portland cement. The
      response surface methodology and central composite design were used to elucidate
      the nature of the response surface in the experimental design and describe the
      optimum conditions of the independent variables, including aeration rate (L/min),
      contact time (h), and ratio of leachate to wastewater mixture (%; v/v), as well
      as their responses (dependent variables). Appropriate conditions of operating
      variables were also optimized to predict the best value of responses. To perform
      an adequate analysis of the aerobic process, four dependent parameters, namely,
      chemical oxygen demand (COD), color, ammonia-nitrogen (NH3-N), and phenols, were
      measured as responses. The results indicated that the PZ-SBR showed higher
      performance in removing certain pollutants compared with SBR. Given the optimal
      conditions of aeration rate (1.74 L/min), leachate to wastewater ratio (20%), and
      contact time (10.31 h) for the PZ-SBR, the removal efficiencies for color, NH3-N,
      COD, and phenols were 84.11%, 99.01%, 72.84%, and 61.32%, respectively.

PMID- 24662111
TI  - Drug-induced thrombocytopenia in the critically ill: a case-control study.
AB  - BACKGROUND: Drugs are suspected when obvious causes of intensive care unit (ICU)
      acquired thrombocytopenia have been excluded. It has been estimated that 10% to
      25% of cases may be drug induced. OBJECTIVES: The objectives of this study were
      to evaluate the risk of thrombocytopenia associated with drug classes commonly
      used in the ICU. METHODS: Data concerning patients admitted for more than 48
      hours between 1997 and 2011 were extracted from a research-purpose database.
      Patients with thrombocytopenia within the first 72 hours of admission and with
      diagnoses or interventions considered strongly associated with thrombocytopenia
      were excluded. Drug exposures were compared and adjusted for confounders using
      conditional logistic regression. RESULTS: A total of 238 cases were identified
      after exclusions. Each case was matched according to sex, age, admission year,
      and admission unit with 1 control. In univariate analysis, quinolones (odds ratio
      [OR] = 1.56; 95% CI = 1.01-2.40) and extended spectrum beta-lactams (OR = 1.71;
      95% CI = 1.00-2.93) were significantly associated with an increased risk of
      thrombocytopenia. After adjusting for confounders, exposure to quinolones was the
      only drug class with a statistically significant increase in risk of
      thrombocytopenia (OR = 1.697; 95% CI = 1.002-2.873; P = 0.049). CONCLUSION: In
      this study of ICU-acquired thrombocytopenia, we found no association between the
      exposures to several antibiotic classes, anticonvulsants, antiplatelet agents,
      nonsteroidal anti-inflammatory agents, and heparins and thrombocytopenia. As
      linezolid was not studied, no conclusions can be drawn concerning this agent. The
      statistically significant association between quinolones and thrombocytopenia
      warrants further investigation.

PMID- 24662112
TI  - Effect of bariatric surgery on hypertension: a meta-analysis.
AB  - PURPOSE: Obesity is a growing epidemic leading to worldwide public health
      concerns. Bariatric surgery is an option for patients with a body mass index
      (BMI) >40 kg/m(2) or BMI of >35 kg/m(2) with serious comorbid conditions. This
      meta-analysis examines the effect of bariatric surgery on the improvement or
      resolution of hypertension. METHODS: Two independent investigators conducted a
      literature search of PubMed (1990-2013) and Cochrane databases using the terms
      bariatric surgery and hypertension to identify appropriate human adult studies
      published in English. Studies were included if they reported the number of
      patients with hypertension prior to undergoing any bariatric surgery procedure
      and whether the hypertension improved or resolved postsurgery. The number of
      patients with hypertension and their response rates were extracted and analyzed
      using RevMan 5.2.5. RESULTS: In all, 31 prospective and 26 retrospective studies
      met all criteria. The types of bariatric surgery performed included Roux-en-Y,
      gastric banding, laparoscopic adjustable gastric banding, vertical gastric
      banding, sleeve gastrectomy, duodenal switch, and biliopancreatic diversion. The
      time to first follow-up after surgery varied from 1 week to 7 years. Of the 57
      studies, 32 reported improvement of hypertension in 32 628 of 51 241 patients
      (odds ratio [OR] = 13.24; 95% CI = 7.73, 22.68; P < 0.00001); 46 studies reported
      the resolution of hypertension in 24 902 of 49 844 patients (OR = 1.70; 95% CI =
      1.13, 2.58; P = 0.01). A random-effects model was used because the heterogeneity
      between the studies was high (I (2) = 97%). CONCLUSION: The results of this meta
      analysis indicate that patients who undergo bariatric surgery experience
      improvement and resolution of their hypertension.

PMID- 24662113
TI  - We have grown.

PMID- 24662114
TI  - Application of stable isotope tracers in the study of exercise metabolism in
      children: a primer.
AB  - Exercise metabolism in children has traditionally been assessed using the
      respiratory exchange ratio (RER) to determine the contributions of fat and
      carbohydrate to the exercise energy demands. Although easily measured, RER
      measurements have limitations. Other methods to assess metabolism such as the
      obtainment of a muscle biopsy and the use of nuclear magnetic resonance
      spectroscopy carry ethical and feasibility concerns, respectively, which limit
      their use in studies involving children. Stable isotopes, used routinely in
      studies involving adults, can also be applied in studies involving children in an
      ethical and feasible manner. Two common stable isotopes used in metabolic studies
      involving children include carbon-13 (13C) and nitrogen-15 (15N). 13C-glucose can
      be used to study carbohydrate metabolism and 15N-glycine can be used to assess
      protein metabolism. This article reviews the use of 13C-glucose and 15N-glycine
      to study exercise metabolism in children, considers some of the associated
      ethical aspects, explains the general methodology involved in administering these
      isotopes and the resources required, and describes studies involving children
      utilizing these methods. Finally, suggestions for future research are provided to
      encourage further use of these techniques.

PMID- 24662110
TI  - Structural changes in hair follicles and sebaceous glands of hairless mice
      following exposure to sulfur mustard.
AB  - Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation,
      edema and blistering. A hallmark of SM-induced toxicity is follicular and
      interfollicular epithelial damage. In the present studies we determined if SM
      induced structural alterations in hair follicles and sebaceous glands were
      correlated with cell damage, inflammation and wound healing. The dorsal skin of
      hairless mice was treated with saturated SM vapor. One to seven days later,
      epithelial cell karyolysis within the hair root sheath, infundibulum and isthmus
      was apparent, along with reduced numbers of sebocytes. Increased numbers of
      utriculi, some with connections to the skin surface, and engorged dermal cysts
      were also evident. This was associated with marked changes in expression of
      markers of DNA damage (phospho-H2A.X), apoptosis (cleaved caspase-3), and wound
      healing (FGFR2 and galectin-3) throughout pilosebaceous units. Conversely, fatty
      acid synthase and galectin-3 were down-regulated in sebocytes after SM. Decreased
      numbers of hair follicles and increased numbers of inflammatory cells surrounding
      the utriculi and follicular cysts were noted within the wound 3-7 days post-SM
      exposure. Expression of phospho-H2A.X, cleaved caspase-3, FGFR2 and galectin-3
      was decreased in dysplastic follicular epidermis. Fourteen days after SM,
      engorged follicular cysts which expressed galectin-3 were noted within
      hyperplastic epidermis. Galectin-3 was also expressed in basal keratinocytes and
      in the first few layers of suprabasal keratinocytes in neoepidermis formed during
      wound healing indicating that this lectin is important in the early stages of
      keratinocyte differentiation. These data indicate that hair follicles and
      sebaceous glands are targets for SM in the skin.

PMID- 24662128
TI  - Amplification and overexpression of TP63 and MYC as biomarkers for transition of
      cervical intraepithelial neoplasia to cervical cancer.
AB  - OBJECTIVE: Biopsy confirmed that cervical intraepithelial neoplasia (CIN) may
      naturally regress or progress. Currently, the risk assessment for CIN progression
      to cervical cancer is still not satisfactory in clinical practice. We
      investigated copy number and protein expression of TP63 and MYC and explored the
      possibility to use them as progression biomarkers. METHODS: Copy numbers of TP63
      and MYC, as well as human papilloma virus (HPV) integration status, were
      determined by fluorescence in situ hybridization in 39 patients with CIN and 66
      patients with cervical cancer. Corresponding protein expressions were analyzed by
      immunohistochemistry. Receiver operating characteristic curves were used to
      measure the diagnostic test performance for the detection of cervical cancer from
      CIN. Sensitivity and specificity values of biomarkers were calculated. RESULTS:
      The average copy number and expression of TP63 and MYC, as well as the HPV
      integration rate, increased in the progression of CIN to cervical cancer.
      Receiver operating characteristic analysis for detection of cervical cancer
      resulted in area under the curve (AUC) values of TP63 copy number (AUC, 0.96; 95%
      confidence interval [CI], 0.91-1.00), MYC copy number (AUC, 0.92; 95% CI, 0.85
      0.96), TP63 expression (AUC, 0.73; 95% CI, 0.61-0.85), and HPV-16 integration
      (AUC, 0.73; 95% CI, 0.60-0.85). MYC expression was not able to statistically
      distinguish cancer from CIN (P = 0.393). The combinations increased the
      specificity slightly but not sensitivity. Among them, TP63 amplification showed
      the best diagnostic performance. CONCLUSIONS: Amplification and overexpression of
      TP63 and MYC, and HPV integration rate, are associated with the transition of CIN
      to cervical cancer. Future studies on these biomarkers will help to assess the
      risk of CIN progression.

PMID- 24662129
TI  - Quality of life after complete lymphadenectomy for vulvar cancer: do women prefer
      sentinel lymph node biopsy?
AB  - OBJECTIVES: Leg lymphoedema occurs in up to 60% of women after a complete
      inguinal-femoral lymphadenectomy for vulvar cancer. To avoid lymphoedema,
      sentinel lymph node biopsy has become the preferred method of staging. However,
      false-negative results may influence survival, making the sentinel node procedure
      unacceptable to many fully informed women. The aims of this study were to measure
      the quality of life (QoL) in women after a complete lymphadenectomy for vulvar
      cancer and to quantify the risk to survival these women would be prepared to take
      with sentinel node biopsy. MATERIALS AND METHODS: Sixty women who had a complete
      lymphadenectomy for early-stage vulvar cancer participated in structured
      interviews. The severity of lymphoedema symptoms was recorded. The QoL-adjusted
      survival was measured using the Utility-Based Questionnaire-Cancer, a cancer
      specific validated QoL instrument. The women stated their preference for sentinel
      node biopsy or complete lymphadenectomy. A "standard-gamble" preference table was
      used to quantify the degree of risk to survival they would take to avoid
      lymphoedema. RESULTS: Seventy-three percent of women reported lymphoedema after
      complete lymphadenectomy. Women with lymphoedema or leg pain had significantly
      worse scores for QoL in terms of social activity as well as physical and sexual
      function. Overall, 80% of women would choose complete lymphadenectomy rather than
      sentinel node biopsy if the risk of missing a positive lymph node was higher than
      1 in 100, but if the risk of missing a positive lymph node was lower than 1 in
      100, almost one third of the women would prefer sentinel node biopsy.
      CONCLUSIONS: Although women treated for early-stage vulvar cancer report reduced
      QoL after complete lymphadenectomy, most would choose complete lymphadenectomy
      over sentinel node biopsy. However, there is an individual level of risk that
      each woman can define with regard to her preference for the sentinel node
      procedure. Women with early-stage vulvar cancer should be offered an informed
      choice between complete lymphadenectomy or sentinel node biopsy.

PMID- 24662130
TI  - Phase II trial on cisplatin-adriamycin-paclitaxel combination as neoadjuvant
      chemotherapy for locally advanced cervical adenocarcinoma.
AB  - OBJECTIVE: Neoadjuvant chemotherapy (NACT) followed by surgery is a different
      therapeutic approach to locally advanced cervical adenocarcinoma (LACA) and seems
      to offer specific advantages over chemoradiation. This phase II trial was
      designed to evaluate the toxicity and activity of NACT with cisplatin-adriamycin
      paclitaxel (TAP) in patients with LACA. METHODS: Patients with International
      Federation of Gynecology and Obstetrics stage IB2-IIB uterine adenocarcinoma were
      treated with NACT TAP for 3 cycles. After the last cycle, patients underwent
      radical surgery with lymph node dissection. Pathological response was classified
      as no residual tumor (pCR), residual disease with less than 3-mm stromal invasion
      (pR1), or residual disease with more than 3-mm stromal invasion (pR2). RESULTS:
      Between 2003 and 2010, 30 women were enrolled. Fourteen complete clinical
      responses, 10 partial responses, and 6 stabilizations of disease were registered.
      Three patients achieved a pCR, 6 a pR1 response, and 21 a pR2 response. At a
      median follow-up of 45 months, progression-free survival and overall survival
      were 37 and 48 months, respectively. Hematologic toxicity was the most relevant
      adverse effect. CONCLUSIONS: The TAP combination seems to be feasible with an
      acceptable toxicity profile and a promising response rate for the treatment of
      LACA.

PMID- 24662131
TI  - S-phase cell cycle arrest, apoptosis, and molecular mechanisms of aplasia ras
      homolog member I-induced human ovarian cancer SKOV3 cell lines.
AB  - OBJECTIVE: Aplasia Ras homolog member I (ARHI) is associated with human ovarian
      cancer (HOC) growth and proliferation; however, the mechanisms are unclear. The
      purpose of this study was to investigate ARHI effects in HOC SKOV3 cells.
      METHODS: We transfected SKOV3 cells with PIRES2-EGFP-ARHI and measured growth
      inhibition rates, cell cycle distribution, apoptosis rates, and expression of P
      STAT3 (phosphorylated signal transduction and activators of transcription 3) and
      P-ERK (phosphorylated extracellular signal regulated protein kinase). RESULTS:
      Our data showed significant inhibition of growth, significantly increased S-phase
      arrest and apoptosis rates, and reduction of P-STAT3 and P-ERK1/2 expression
      levels. CONCLUSIONS: We propose the mechanism may involve ARHI-induced
      phosphorylation of ERK1/2 and STAT3 protein kinases, thereby blocking
      proliferation signaling pathways, to induce HOC SKOV3 apoptosis.

PMID- 24662132
TI  - Prediction of para-aortic spread by gross pelvic lymph node findings in patients
      with endometrial carcinoma.
AB  - OBJECTIVE: Isolated para-aortic lymph node metastases are rare in patients with
      endometrial carcinoma. We wanted to determine the reliability of macroscopic
      pelvic lymph node findings at surgery in predicting para-aortic space involvement
      in these patients. METHODS: We identified all women with surgically treated
      endometrial carcinoma at our institution between January 2008 and February 2013
      (n = 854). One hundred seventeen patients received pelvic-aortic lymphadenectomy.
      Lymph nodes were considered grossly positive based on size and morphology.
      RESULTS: In patients who underwent comprehensive lymphadenectomy, grossly
      positive pelvic nodes predicted para-aortic metastasis with a sensitivity of
      52.4% and specificity of 93.8%. The positive and negative likelihood ratios were
      8.4 and 0.51, respectively. The predictive power of grossly positive pelvic nodes
      remained significant (odds ratio, 18; 95% confidence interval, 4.1-78; P <
      0.0001) after correcting for deep myometrial invasion, poor tumor
      differentiation, and nonendometrioid histology as confounders. The whole sample
      of 854 patients was used for Bayesian calculations. The cutoff for a clinically
      useful test was set at the negative predictive value of 98.0%. The negative
      predictive value of the test (ie, grossly positive pelvic nodes at surgery in
      predicting the likelihood of para-aortic metastasis) was 99.7% for patients with
      superficial grade 1 to 2 endometrioid carcinomas and 98.0% for patients with
      deeply invasive grade 1 to 2 endometrioid carcinomas. For patients with grade 3
      endometrioid and nonendometrioid carcinomas, the negative predictive values were
      97.3% and 92.2%, respectively. For the whole study population, the value was
      98.4%. CONCLUSIONS: When uterine factors are used for risk stratification of
      endometrial carcinomas, selective para-aortic lymphadenectomy, based on gross
      findings of pelvic nodes, is feasible for patients with grade 1 to 2 endometrioid
      carcinomas, regardless of the depth of myometrial invasion. Similarly, gross
      findings of pelvic nodes can be used to evaluate the need for para-aortic
      lymphadenectomy in the strategy of routine pelvic lymphadenectomy.

PMID- 24662133
TI  - Radiotherapy- or radical surgery-induced female sexual morbidity in stages IB and
      II cervical cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the sexual function in
      cervical cancer survivors after radiotherapy (RT) or radical surgery (RS).
      METHODS: This was an observational and cross-sectional study. The Female Sexual
      Function Index (FSFI) self-reported questionnaires were distributed to 175
      patients after RT (RT group) or RS (RS group) and 521 healthy women (control)
      between 2011 and 2012. Sexual functions were compared among these 3 groups.
      RESULTS: Eligible 92 patients (46 in RT group, 46 in RS group) and 148 control
      subjects were included for analysis. There was a significant difference in median
      (range) FSFI total score of 5.5 (3.6-34.7) in the RT group, 18.9 (3.4-31.2) in
      the RS group, and 22.1 (2-34.2) in the control group (P < 0.001). The median FSFI
      total score in the RT group was significantly lower than that in the control
      group (P < 0.001). Six sexual domains (desire, arousal, lubrication, orgasm,
      satisfaction, pain) were all significantly affected in the RT group, and no
      significant differences, except pain, were observed in the RS group as compared
      with the control group. CONCLUSIONS: Interventions involving counseling and
      rehabilitation for female sexual function should be provided in cervical cancer
      survivors, especially after RT.

PMID- 24662134
TI  - Survivin expression as a prognostic factor in patients with epithelial ovarian
      cancer or primary peritoneal cancer treated with neoadjuvant chemotherapy.
AB  - BACKGROUND: The aim of this study was to evaluate association of expression of
      survivin and p53 with the effects of neoadjuvant chemotherapy (NAC) in patients
      with advanced ovarian cancer (AOC). METHODS: We retrospectively evaluated 60
      consecutive patients with AOC (International Federation of Gynecology and
      Obstetrics stage IIIC-IV) treated with NAC. The expression of p53 and survivin
      was assessed immunohistochemically. The median of expression total score survivin
      equals 2 was adopted to dichotomize the group. The positive and negative
      expression of p53 was used to dichotomize the group. RESULTS: The expression of
      survivin in tumor tissue taken before and after NAC was a significant difference
      in the percentage of stained nuclei (P = 0.0002), the intensity of staining (P =
      0.0003), and total score (P = 0.0001). There was a significant difference in p53
      expression in tumor tissue before and after NAC in the percentage of stained
      nuclei (P = 0.0424). Survivin expression, in contrast to p53 expression, was a
      prognostic factor in patients with AOC treated with NAC (P = 0.0484). The
      expression of survivin and p53 was not a predictive factor. Independent adverse
      predictor factors were as follows: lack of optimal interval debulking surgery and
      the lack of an objective response (the respective hazard ratio was 3.93 [95%
      confidence interval, 2.07-7.46; P < 0.0001] and 2.36 [95% confidence
      interval,1.25-4.47; P = 0.0080]). The suboptimal range of interval debulking
      surgery, resistance to platinum, and the lack of paclitaxel in the NAC were
      adverse prognostic factors (the respective hazard ratio was 2.61 [95% confidence
      interval, 1.17-5.83], 2.72 [95% confidence interval, 1.07-6.89], and 2.56 [95%
      confidence interval, 1.06-6.18]; P < 0.05]). CONCLUSIONS: High expression of
      survivin could be a prognostic factor in patients treated with NAC for AOC.

PMID- 24662135
TI  - The link between endometriosis and ovarian cancer: clinical implications.
AB  - OBJECTIVES: The objectives of this study were to evaluate the current evidence of
      the association of endometriosis and subsequent carcinoma of the ovary and to
      contextualize this evidence into daily practice issues. METHODS: This study is a
      critical review of observational and in vitro studies. RESULTS: Although the
      lifetime risk for ovarian cancer is low in general population and remains low in
      the broad spectrum of endometriosis, there may be clusters of individuals at
      higher risk of oncogenesis, whose identification would allow individualized
      surveillance and prophylactic interventions. Prevalence studies show that
      specific subtypes of ovarian cancer predominate in women with endometriosis. This
      has been validated in pathogenetic, genomic, immunobiologic, and hormonal
      studies. CONCLUSIONS: Taken together, these data provide a strong rationale for
      identifying, monitoring, counseling, and treating women with endometriosis who
      are at highest risk for cancer conversion.

PMID- 24662136
TI  - Lymph node count at inguinofemoral lymphadenectomy and groin recurrences in
      vulvar cancer.
AB  - OBJECTIVE: The objective of the study is to determine the risk factors for groin
      recurrence (GR) in patients with primary vulvar squamous cell carcinoma (SCC)
      after inguinofemoral lymphadenectomy (IFL) without lymph node metastases and/or
      adjuvant chemoradiotherapy. METHODS: The study is a multicenter retrospective
      review of clinical and histopathological data of patients with lymph node
      negative vulvar SCC who underwent an IFL. Patients with and without GRs were
      compared to identify risk factors. RESULTS: In 134 patients, 252 groins were
      eligible for the analyses--16 patients underwent ipsilateral IFL and 118 patients
      underwent bilateral IFL. Groin recurrences occurred in 4 (1.6%) of the 252
      dissected groins. Besides, 1 patient who underwent ipsilateral IFL had a
      recurrence in the nonoperated contralateral groin; this groin was left out of
      analysis. The median number of dissected nodes per groin was 9.8 (range, 1-38) in
      all patients and 6.5 (range, 5-8) in patients with GR. Multivariate analyses
      showed that GR was related to poor differentiation (P = 0.04), and node count
      less than 9 (P = 0.04), no association with age, tumor localization, tumor
      diameter, focality, invasion depth, or stage was found. Nineteen patients with
      both low node count and poor differentiation had 19% GRs. Survival analyses
      showed less favorable survival in patients with poor differentiation.
      CONCLUSIONS: The overall risk of developing GR after negative IFL in patients
      with vulvar SCC is low (1.6% per groin) but significantly higher in patients with
      tumors with a poor differentiation and lymph node count less than 9 at IFL. A
      large well-designed prospective study is needed to evaluate closer surveillance
      in patients at risk.

PMID- 24662137
TI  - Bacterial biofilm in chronic venous ulcer.

PMID- 24662138
TI  - Prevalence, risk factors and genotypes of hepatitis B infection among HIV
      infected patients in the State of MS, Central Brazil.
AB  - OBJECTIVES: A cross-sectional study on prevalence of HBV and HDV infection, risk
      factors and genotype distribution of HBV infection was conducted among 848 HIV
      infected patients in Mato Grosso do Sul, Central Brazil. METHODS: Serum samples
      of 848 participants were tested for hepatitis B surface antigen (HBsAg),
      hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs).
      HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV,
      and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction.
      Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then
      purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi
      square test and Fisher's exact test were used to compare variables and to
      evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg
      positivity) and risk factors. RESULTS: Among the 848 HIV infected patients
      investigated 222 had serological markers of HBV infection. The prevalence rate of
      HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4-3.5%); 484 (57.1%) patients
      were susceptible for HBV infection. There were no cases of anti-HDV positive and
      only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients.
      Male gender, increasing age, family history of hepatitis, use of illicit drug,
      and homosexual activity were independent factors associated with HBV exposure.
      The phylogenetic analysis based on the S gene region revealed the presence of
      genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample. CONCLUSION: This
      study demonstrates the low prevalence of HIV-HBV infection and also highlights
      the need for early vaccination against HBV as well as testing for HBV, HCV and
      HDV in all HIV-infected individuals.

PMID- 24662139
TI  - Incidence of antiretroviral adverse drug reactions in pregnant women in two
      referral centers for HIV prevention of mother-to-child-transmission care and
      research in Rio de Janeiro, Brazil.
AB  - Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV)
      infection remains an important cause of new HIV infections worldwide, especially
      in low and middle-resource limited countries. Safety data from studies involving
      pregnant women and prenatal antiretroviral (ARV) exposure are still needed once
      these studies are often small and with a limited duration to assess adverse drug
      reactions (ADR). The aim of this study was to estimate the incidence of ADR
      related to the use of antiretroviral therapy (ART) in pregnant women in two
      referral centers in Rio de Janeiro State. A prospective study was carried out
      from February 2005 to May 2006. Women were classified according to their ART
      status during pregnancy diagnosis: ARV-experienced (ARTexp) or ARV-naive (ARTn).
      Two hundred fourteen HIV-infected pregnant women were included: 36 ARTexp and 178
      ARTn. ARTexp women have not experienced ADR. Among ARTn, 20.2% presented ADR.
      Incidence rate of ADR was 70.8 per 1000 person-months and the most common ADRs
      observed were: gastrointestinal (belly or abdominal cramps, diarrhea, nausea and
      vomit) in 16.3%, cutaneous (pruritus and rash) in 6.2%, anemia (2.2%) and
      hepatitis (1.7%). The frequency of obstetrical complications, pre-term delivery,
      low birth weight and birth abnormalities was low in this population. ADRs ranged
      from mild to moderate intensity, none of them being potentially fatal. Only in a
      few cases it was necessary to discontinue ART. In conclusion, the high
      effectiveness of ARV for HIV prevention of MTCT (PMTCT) overcomes the risk of
      ADR. 

PMID- 24662140
TI  - Adherence to acute otitis media treatment guidelines among primary health care
      providers in Israel.
AB  - AIMS: To determine the appropriateness of the acute otitis media antibiotic
      treatment prescribed in the community in relation to the therapeutic guidelines.
      METHODS: Children aged 3 months-3 years diagnosed with simple uncomplicated acute
      otitis media in 6 community primary care clinics were enrolled. Data on the
      antibiotic treatment were collected using computerized medical files. RESULTS:
      689 simple uncomplicated acute otitis media patients were enrolled; 597 (86.9%)
      were treated with antibiotics by 38 family medicine practitioners, 12
      pediatricians and 7 general practitioners. 461 (77.2%) patients were <2 years of
      age. Amoxicillin was administered to 540 (90.5%) patients, with no differences
      between the various medical specialties. 127/540 (23.5%) patients did not receive
      the appropriate dosage; 140/413 (33.9%) patients treated with appropriate dosage
      did not receive the treatment for the appropriate duration of time. 258/357
      (72.3%) evaluable patients <2 years of age received an antibiotic considered
      inappropriate to guidelines (38 not treated with amoxicillin, 94 received
      inappropriate dosage and 126 not treated for 10 days); 53/100 (53%) evaluable
      children >2 years of age received an inappropriate antibiotic treatment.
      CONCLUSIONS: The majority of primary care physicians treat simple uncomplicated
      acute otitis media with the recommended antibiotic drug. However, incorrect
      dosage and shorter than recommended duration of therapy may jeopardize the
      quality of care in children with simple uncomplicated acute otitis media.

PMID- 24662141
TI  - Congenital toxoplasmosis in a reference center of Parana, Southern Brazil.
AB  - This study describes the characteristics of 31 children with congenital
      toxoplasmosis children admitted to the University Hospital of Londrina, Southern
      Brazil, from 2000 to 2010. In total, 23 (85.2%) of the mothers received prenatal
      care but only four (13.0%) were treated for toxoplasmosis. Birth weight was
      <2500g in 37.9% of the infants. During the first month of life, physical
      examination was normal in 34.5%, and for those with clinical signs and symptoms,
      the main manifestations were hepatomegaly and/or splenomegaly (62.1%), jaundice
      (13.8%), and microcephaly (6.9%). During ophthalmic examination, 74.2% of the
      children exhibited injuries, 58.1% chorioretinitis, 32.3% strabismus, 19.4%
      microphthalmia, and 16.2% vitreitis. Anti-Toxoplasma gondii IgM antibodies were
      detected in 48.3% of the children. Imaging brain evaluation was normal in 44.8%;
      brain calcifications, hydrocephaly, or both conditions were observed in 27.6%,
      10.3%, and 17.2%, respectively, of the patients. Patients with cerebrospinal
      fluid protein>=200mg/dL presented more brain calcifications (p=0.0325). Other
      sequelae were visual impairment (55.2% of the cases), developmental delay
      (31.0%), motor deficit (13.8%), convulsion (27.5%), and attention deficit
      (10.3%). All patients were treated with sulfadiazine, pyrimethamine, and folinic
      acid, and 55.2% of them exhibited adverse effects. The results demonstrate the
      significance of the early diagnosis and treatment of toxoplasmosis during
      pregnancy to reduce congenital toxoplasmosis and its consequences. 

PMID- 24662142
TI  - AIDS and disseminated tuberculosis after Immune Reconstitution Inflammatory
      Syndrome.

PMID- 24662143
TI  - Application of high-speed counter-current chromatography combined with
      macroporous resin for rapid enrichment and separation of three anthraquinone
      glycosides and one stilbene glycoside from Rheum tanguticum.
AB  - In this paper, an efficient method was successfully established by the
      combination of macroporous resin (MR) and high-speed counter-current
      chromatography (HSCCC) for rapid enrichment and separation of aloe-emodin 8-O
      beta-D-glucoside, emodin 1-O-beta-D-glucoside, emodin 8-O-beta-D-glucoside and
      piceatannol 4'-O-beta-D-(6"-O-gallate)-glucoside. Six kinds of macroporous resins
      were investigated in the first step and X-5 macroporous resin was selected for
      the enrichment of the target compounds. The recoveries of the target compounds
      reached 89.0, 85.9, 82.3 and 84.9% respectively after 40% ethanol elution. In the
      second step, the target compounds were separated by HSCCC with a two-phase
      solvent system composed of chloroform/ethyl acetate/methanol/water (8:1:6:5,
      v/v). The established method will be helpful for further characterization and
      utilization of Rheum tanguticum. The results demonstrate that MR coupled with
      HSCCC is a powerful technique for separation of bioactive compounds from natural
      products. 

PMID- 24662144
TI  - Simultaneous determination of four bioactive flavonoids from Polygonum orientale
      L. in dog plasma by UPLC-ESI-MS/MS and application of the technique to
      pharmacokinetic studies.
AB  - The in vivo effects of traditional herbal medicines are generally mediated by
      multiple bioactive components. The main constituents of Polygonum orientale L.
      are flavonoids such as orientin, vitexin, cynaroside, and quercitrin. The aim of
      this study was to develop and validate a method for characterizing these
      flavonoids, in order to better understand the pharmacokinetics and
      pharmacodynamics of P. orientale L. We used ultra-performance liquid
      chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)
      to analyze the flavonoids. After precipitation of the proteins with methanol, the
      flavonoids were separated on a BEH C18 column (50mm*2.1mm, i.d., 1.7MUm) by using
      an elution gradient of acetonitrile. Flavonoid content was determined using the
      multiple reaction monitoring (MRM) mode at m/z 449.2->329.2 for orientin, m/z
      433.2->313.0 for vitexin, m/z 449.2->287.1 for cynaroside, m/z 449.2->303.4 for
      quercitrin, and m/z 417.0->267.0 for the internal standard, puerarin.
      Pharmacokinetics was assessed after intravenous administration of P. orientale L.
      extracts (POE) in Beagle dogs at a dose of 22, 44, or 88mg/kg. Analysis of the
      standard curves by linear regression revealed high linearity over a 243-fold
      dynamic range for the four flavonoids (the lower limit of quantitation values
      were 4-21ng/mL). The relative standard deviations of intra- and inter-day
      measurements were less than 15.1%, and the method was accurate to within -8.7% to
      7.2%; the extraction recoveries from dog plasma were 70.6-89.3%, 69.8-88.7%, 72.5
      85.7%, and 71.0-79.1% for orientin, vitexin, cynaroside, and quercitrin,
      respectively. Our results suggest non-linear pharmacokinetic characteristics with
      rapid clearance of the flavonoids. In conclusion, UPLC-ESI-MS/MS is a rapid and
      sensitive method for simultaneous quantification of multiple flavonoids from POE
      in dog plasma and is suitable for pharmacokinetic studies of herbal medicines. 

PMID- 24662145
TI  - Metabolic versatility in methanogens.
AB  - Methanogenesis is an anaerobic metabolism responsible for the generation of >90%
      of the methane formed on Earth today, with important implications for fuels
      production and global warming. Although methanogenic Archaea have been cultured
      for over 70 years, key insights regarding electron flow and energy conservation
      in methanogenesis have only recently emerged. Fundamental differences between two
      metabolic types of methanogenesis, hydrogenotrophic and methylotrophic, are now
      understood, with implications for metabolic versatility and the potential for
      engineering of methanogens to utilize new substrates. The development of model
      species with genetic and bioinformatic tools has advanced the field and holds
      potential for further characterizing and engineering of methanogenesis. Our
      understanding of a related pathway, anaerobic methane oxidation, is in its
      infancy. 

PMID- 24662146
TI  - Histopathology of motor cortex in an experimental focal ischemic stroke in mouse
      model.
AB  - Experimental ischemia results in cortical brain lesion followed by ischemic
      stroke. In this study, focal cerebral ischemia was induced in mice by occlusion
      of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in
      the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and
      C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm
      motor cortex, significant differences were observed in the numbers of neurons,
      astrocytes and microglia in the superficial II/III and deep V cortical layers.
      Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis,
      chromatin fragmentation, necrosis and degeneration, as well as, morphological
      evidence of apoptosis, mainly in neurons. As result, the CFA was more severely
      impaired than the AGm in this focal cerebral ischemic model, as evidenced by the
      proliferation of astrocytes, potentially resulting in neuroinflammation by
      microglia-like cells. 

PMID- 24662147
TI  - Functional diversity of five homologous Cu+-ATPases present in Sinorhizobium
      meliloti.
AB  - Copper is an important element in host-microbe interactions, acting both as a
      catalyst in enzymes and as a potential toxin. Cu(+)-ATPases drive cytoplasmic
      Cu(+) efflux and protect bacteria against metal overload. Many pathogenic and
      symbiotic bacteria contain multiple Cu(+)-ATPase genes within particular genetic
      environments, suggesting alternative roles for each resulting protein. This
      hypothesis was tested by characterizing five homologous Cu(+)-ATPases present in
      the symbiotic organism Sinorhizobium meliloti. Mutation of each gene led to
      different phenotypes and abnormal nodule development in the alfalfa host.
      Distinct responses were detected in free-living S. meliloti mutant strains
      exposed to metal and redox stresses. Differential gene expression was detected
      under Cu(+), oxygen or nitrosative stress. These observations suggest that CopA1a
      maintains the cytoplasmic Cu(+) quota and its expression is controlled by Cu(+)
      levels. CopA1b is also regulated by Cu(+) concentrations and is required during
      symbiosis for bacteroid maturation. CopA2-like proteins, FixI1 and FixI2, are
      necessary for the assembly of two different cytochrome c oxidases at different
      stages of bacterial life. CopA3 is a phylogenetically distinct Cu(+)-ATPase that
      does not contribute to Cu(+) tolerance. It is regulated by redox stress and
      required during symbiosis. We postulated a model where non-redundant homologous
      Cu(+)-ATPases, operating under distinct regulation, transport Cu(+) to different
      target proteins. 

PMID- 24662149
TI  - Doctor who carried out three abortions as favour to colleague is allowed to
      resume unrestricted practice.

PMID- 24662148
TI  - Anti-ribosomal-P antibodies accelerate lupus glomerulonephritis and induce lupus
      nephritis in naive mice.
AB  - BACKGROUND: Lupus nephritis is known to be associated with several antibodies
      including autoantibodies that target the DNA, C1q and histone, alpha-actinin, and
      the nucleosome. In addition, circulating anti-phosphoribosomal protein antibodies
      (anti-Ribos.P) were found to be associated with lupus nephritis. STUDY OBJECTIVE:
      We have assessed the direct role of anti-Ribos.P in the development of
      glomerulonephritis in-vitro and in animal models. STUDY DESIGN: NZBxW/F1 lupus
      prone mice were immunized with recombinant Ribos.P0 (rRibos.P). Evaluation of
      renal disease included mice evaluation for proteinuria and histologic analysis of
      the kidneys. Anti-Ribos.P monoclonal Ab was prepared from the rRibos.P immunized
      NZBxW/F1 mice by hybridoma technology. MAPKs expression was analyzed by MAPKs
      protein array and confirmed by real-time PCR and western blot. To elucidate
      whether anti-Ribos.P induce glomerulonephritis, naive C3H mice were immunized
      with recombinant rRibos.P and the glomerulonephritis was followed up as described
      above. RESULTS: The immunized NZBxW/F1 lupus prone mice developed anti-Ribos.P
      which was cross reactive with Sm and not dsDNA. The mice developed accelerated
      glomerulonephritis manifested by early proteinuria and immunoglobulin deposites
      in the mesangium of the kidneys. Anti-Ribos.P deposited in the glomerular
      mesangium were eluted from the kidney. The Ribos.P immunized naive C3H/Hen mice
      developed glomerulonephritis manifested by circulating autoantibodies directed to
      Ribos.P, dsDNA and Sm. The anti Ribos.P were cross reactive with Sm but not with
      dsDNA, and were deposited in the glomeruli. Interestingly these mice developed
      alopecia. In vitro. Primary mesangial cells exposed to mouse anti-Ribos.P mAb
      originated from the immunized lupus mice and to human anti-Ribos.P Abs, induced
      activation of mesangial cells via p38alpha, JNK, AKT and HSP27 MAPKs expression
      pathway. CONCLUSIONS: Our data show for the first time that anti-Ribos.P are
      nephritogenic autoantibodies, as illustrated by in-vitro and in-vivo experiments:
      a) They accelerate the development of glomerulonephritis in lupus prone mice; b)
      They induce nephritis in naive mice. c) Anti-Ribos.P Abs trigger MAPKs expression
      in primary mesangial cells. These data contribute a direct mechanistic link
      between anti-Ribos.P and nephritis in lupus mice.

PMID- 24662150
TI  - Revealing the cerebral regions and networks mediating vulnerability to
      depression: oxidative metabolism mapping of rat brain.
AB  - The large variety of available animal models has revealed much on the
      neurobiology of depression, but each model appears as specific to a significant
      extent, and distinction between stress response, pathogenesis of depression and
      underlying vulnerability is difficult to make. Evidence from epidemiological
      studies suggests that depression occurs in biologically predisposed subjects
      under impact of adverse life events. We applied the diathesis-stress concept to
      reveal brain regions and functional networks that mediate vulnerability to
      depression and response to chronic stress by collapsing data on cerebral long
      term neuronal activity as measured by cytochrome c oxidase histochemistry in
      distinct animal models. Rats were rendered vulnerable to depression either by
      partial serotonergic lesion or by maternal deprivation, or selected for a
      vulnerable phenotype (low positive affect, low novelty-related activity or high
      hedonic response). Environmental adversity was brought about by applying chronic
      variable stress or chronic social defeat. Several brain regions, most
      significantly median raphe, habenula, retrosplenial cortex and reticular
      thalamus, were universally implicated in long-term metabolic stress response,
      vulnerability to depression, or both. Vulnerability was associated with higher
      oxidative metabolism levels as compared to resilience to chronic stress. Chronic
      stress, in contrast, had three distinct patterns of effect on oxidative
      metabolism in vulnerable vs. resilient animals. In general, associations between
      regional activities in several brain circuits were strongest in vulnerable
      animals, and chronic stress disrupted this interrelatedness. These findings
      highlight networks that underlie resilience to stress, and the distinct response
      to stress that occurs in vulnerable subjects. 

PMID- 24662151
TI  - Chronic corticosterone administration facilitates aversive memory retrieval and
      increases GR/NOS immunoreactivity.
AB  - Glucocorticoids are stress hormones that mediate the organism's reaction to
      stress. It has been previously proposed that the facilitation of emotional
      aversive conditioning induced by these hormones may involve nitric oxide
      pathways. The purpose of the present study was to address this question. For
      that, male Wistar rats were surgically implanted with slow-release corticosterone
      (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task.
      Additional groups of animals were also submitted to the same treatment conditions
      and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS
      (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of
      plasma CORT. Results showed that CORT treatment induced facilitation of step-down
      inhibitory avoidance. This same treatment also significantly increased CORT
      plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the
      paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate
      gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions.
      Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment
      in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum,
      in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results
      indicate that the facilitation of aversive conditioning induced by CORT involves
      GR-nNOS pathways activation, what may be of relevance for a better understanding
      of stress-related psychiatric conditions. 

PMID- 24662152
TI  - Risk factors associated with complications in lower-extremity reconstruction with
      the distally based sural flap: a systematic review and pooled analysis.
AB  - The distally based sural fasciocutaneous flap is one of the few options available
      for local flap reconstruction of soft-tissue defects in the lower one-third of
      the leg. Few studies have assessed risk factors associated with poor outcomes in
      this flap. A literature search was performed of MEDLINE, EMBASE, CINAHL and the
      Cochrane Library for articles evaluating the use of sural artery fasciocutaneous
      flaps for soft-tissue reconstruction of the leg. Data were pooled and a
      univariate analysis was performed to identify characteristics associated with
      increased morbidity. A logistic regression model was created, and odds ratios and
      p values associated with the development of complications were calculated. Sixty
      one papers were identified which included data on 907 patients. The majority of
      sural flaps were used to cover defects of the heel (28.2%), foot (14.4%) or ankle
      (25.8%). Trauma was the most common indication, followed by ulcers and open
      fractures. Flap complications were recorded in 26.4% of cases with a flap loss
      rate of 3.2%. With multivariate analysis, venous insufficiency and increasing age
      were independent risk factors for complications. Patients with venous
      insufficiency had nine times the risk of developing a complication compared to
      patients without venous insufficiency. 

PMID- 24662153
TI  - Dermal flaps in breast reduction: prospective study in 100 breasts.
AB  - The most common complication of breast reduction with inverted T-scar technique
      is wound dehiscence at the junction of the vertical and horizontal sutures. In
      this study, a technique involving three triangular dermal flaps is presented with
      the results for healing in the junctional T zone. Fifty women were included in a
      comparative, single-center randomized double-blind prospective study to evaluate
      the efficiency of the three-triangular dermal-flap technique in healing in the
      junctional T zone. All patients were seen for follow-up at 7 days, 14 days, 21
      days, 28 days, 35 days, 42 days, and 49 days after surgery to evaluate primary
      healing in the T zone. Average healing time was 19.7 days in the triangular-skin
      flap series and 25.48 days in the control series, with a statistically
      significant difference (p < 0.01). One patient in the triangular-skin-flap series
      experienced dehiscence in the T zone (2%) versus eight patients (16%) in the
      control series. A statistically significant difference was noted (p = 0.012).
      This technique is based on the association of two principles. First, ischemia on
      the edges as well as skin necrosis is limited by suturing the two superior skin
      flaps rather than directly suturing the cutaneous angles. In addition, this
      technique brings an underlying dermal support. Second, the inferior flap width
      allows fixing two sutures laterally to limit the central tension. This easy
      technique does not lengthen total operative time and significantly improves
      healing time. It is applicable to all breast reductions with inverted T scars.

PMID- 24662154
TI  - Functional movement screen scores in a group of running athletes.
AB  - The purpose of this study was to determine the mean values of the functional
      movement screen (FMS) in a group of long-distance runners. The secondary aims
      were to investigate whether the FMS performance differed between sexes and
      between young and older runners. Forty-three runners, 16 women (mean age = 33.5
      years, height = 165.2 cm, weight = 56.3 kg, and body mass index [BMI] = 20.6) and
      27 men (mean age = 39.3 years, height = 177.6 cm, weight = 75.8 kg, and BMI =
      24.2) performed the FMS. All the runners were injury-free and ran >30 km.wk.
      Independent t-tests were performed on the composite scores to examine the
      differences between men and women and also between young (<40 years) and older
      runners (>40 years). Contingency tables (2 * 2) were developed for each of the 7
      screening tests to further look at the differences in groups for each single
      test. The chi values were calculated to determine significant differences.
      Statistical significance was set at p <= 0.05. There was no significant
      difference in the composite score between women and men. There were significant
      differences between the sexes in the push-up and straight leg test scores, with
      the women scoring better on each test. A significant difference was found in the
      composite scores between younger and older runners (p < 0.000). Additional score
      differences were found for the squat, hurdle step, and in-line lunge tests with
      the younger runners scoring better. This study provided mean values for the FMS
      in a cohort of long-distance runners. These values can be used as a reference for
      comparing FMST scores in other runners who are screened with this tool.

PMID- 24662155
TI  - The effects of high intensity short rest resistance exercise on muscle damage
      markers in men and women.
AB  - Within and between sexes, universal load prescription (as assigned in extreme
      conditioning programs) creates extreme ranges in individual training intensities.
      Exercise intensity has been proposed to be the main factor determining the degree
      of muscle damage. Thus, the purpose of this study was to examine markers of
      muscle damage in resistance-trained men (n = 9) and women (n = 9) from a high
      intensity (HI) short rest (SR) (HI/SR) resistance exercise protocol. The HI/SR
      consisted of a descending pyramid scheme starting at 10 repetitions, decreasing 1
      repetition per set for the back squat, bench press, and deadlift, as fast as
      possible. Blood was drawn pre-exercise (pre), immediately postexercise (IP), 15
      minutes postexercise (+15), 60 minutes postexercise (+60), and 24 hours
      postexercise (+24). Women demonstrated significant increases in interleukin 6 (IL
      6; IP), creatine kinase (CK; +24), myoglobin (IP, +15, +60), and a greater
      relative increase when compared with men (+15, +60). Men demonstrated significant
      increases in myoglobin (IP, +15, +60, +24), IL-6 (IP, +15), CK (IP, +60, +24),
      and testosterone (IP, +15). There were significant sex interactions observed in
      CK (IP, +60, +24) and testosterone (IP, +15, +60, +24). Women completed the
      protocol faster (women: 34:04 +/- 9:40 minutes, men: 39:22 +/- 14:43 minutes),
      and at a slightly higher intensity (women: 70.1 +/- 3.5%, men 68.8 +/- 3.1%);
      however, men performed significantly more work (men: 14384.6 +/- 1854.5 kg,
      women: 8774.7 +/- 1612.7 kg). Overall, women demonstrated a faster inflammatory
      response with increased acute damage, whereas men demonstrated a greater
      prolonged damage response. Therefore, strength and conditioning professionals
      need to be aware of the level of stress imposed on individuals when creating such
      volitional high intensity metabolic type workouts and allow for adequate
      progression and recovery from such workouts.

PMID- 24662157
TI  - Effects of grip width on muscle strength and activation in the lat pull-down.
AB  - The lat pull-down is one of the most popular compound back exercises. Still, it
      is a general belief that a wider grip activates the latissimus dorsi more than a
      narrow one, but without any broad scientific support. The aim of the study was to
      compare 6 repetition maximum (6RM) load and electromyographic (EMG) activity in
      the lat pull-down using 3 different pronated grip widths. Fifteen men performed
      6RM in the lat pull-down with narrow, medium, and wide grips (1, 1.5, and 2 times
      the biacromial distance) in a randomized and counterbalanced order. The 6RM
      strengths with narrow (80.3 +/- 7.2 kg) and medium grip (80 +/- 7.1 kg) were
      higher than wide grip (77.3 +/- 6.3 kg; p = 0.02). There was similar EMG
      activation between grip widths for latissimus, trapezius, or infraspinatus, but a
      tendency for biceps brachii activation to be greater for medium vs. narrow (p =
      0.09), when the entire movement was analyzed. Analyzing the concentric phase
      separately revealed greater biceps brachii activation using the medium vs. narrow
      grip (p = 0.03). In the eccentric phase, there was greater activation using wide
      vs. narrow grip for latissimus and infraspinatus (p <= 0.04), and tendencies for
      medium greater than narrow for latissimus, and medium greater than wide for
      biceps (both p = 0.08), was observed. Collectively, a medium grip may have some
      minor advantages over small and wide grips; however, athletes and others engaged
      in resistance training can generally expect similar muscle activation which in
      turn should result in similar hypertrophy gains with a grip width that is 1-2
      times the biacromial distance.

PMID- 24662156
TI  - Effects of fatigue from resistance training on barbell back squat biomechanics.
AB  - Exhaustive resistance training programs that have been previously referred to as
      extreme conditioning protocols have increased in popularity in military and
      civilian populations in recent years. However, because of their highly fatiguing
      nature, proprioception is likely altered during such programs that would
      significantly affect the safety and efficacy of such programs. Therefore, the
      purpose of this study was to assess the alterations in movement patterns that
      result from extreme conditioning protocols and to evaluate if these protocols can
      be deemed safe and effective. Twelve men (age 24 +/- 4.2 years, height 173.1 +/-
      3.6 cm, weight 76.9 +/- 7.8 kg, body fat percentage 9.0 +/- 2.2%) and 13 women
      (age 24.5 +/- 3.8 years, height 166.9 +/- 8.5 cm, weight 66.1 +/- 9.2 kg, body
      fat percentage 18.6 +/- 4.0%) with at least 6 months of resistance training
      experience involving barbell bench press, barbell deadlift, and barbell back
      squat performed a highly fatiguing resistance training workout. During the
      barbell back squat, a 2-dimensional analysis was performed where the knee and hip
      angles were recorded throughout the 55 repetitions of the workout. At the early
      stages of the protocol, knee angle was significantly lower in men and in women
      demonstrating less knee flexion. Also, hip angle was significantly lower early in
      the program in men and in women, demonstrating a greater forward lean. The
      technique changes that occur in high repetition sets do not favor optimal
      strength development and may increase the risk of injury, clearly questioning the
      safety and efficacy of such resistance training programming. This is likely a
      display of self-preservation by individuals who are faced with high repetition
      programs.

PMID- 24662158
TI  - Mumps outbreak.

PMID- 24662159
TI  - Intranasal naloxone for treatment of opioid overdose.

PMID- 24662160
TI  - Ammonia as a case study for the spontaneous ionization of a simple hydrogen
      bonded compound.
AB  - Modern ab initio calculations predict ionic and superionic states in highly
      compressed water and ammonia. The prediction apparently contradicts state-of-the
      art experimentally established phase diagrams overwhelmingly dominated by
      molecular phases. Here we present experimental evidence that the threshold
      pressure of ~120 GPa induces in molecular ammonia the process of autoionization
      to yet experimentally unknown ionic compound--ammonium amide. Our supplementary
      theoretical simulations provide valuable insight into the mechanism of
      autoionization showing no hydrogen bond symmetrization along the transformation
      path, a remarkably small energy barrier between competing phases and the impact
      of structural rearrangement contribution on the overall conversion rate. This
      discovery is bridging theory and experiment thus opening new possibilities for
      studying molecular interactions in hydrogen-bonded systems. Experimental
      knowledge on this novel ionic phase of ammonia also provides strong motivation
      for reconsideration of the theory of molecular ice layers formation and dynamics
      in giant gas planets.

PMID- 24662162
TI  - Vitamin D intake and status in 12-month-old infants at 63-66 degrees  N.
AB  - The objective was to assess the vitamin D status in healthy 12-month-old infants
      in relation to quantity and sources of dietary vitamin D, breastfeeding and
      seasons. Subjects were 76 12-month-old infants. Serum levels of 25-hydroxyvitamin
      D (25(OH)D) >= 50 nmol/L were considered indicative of vitamin D sufficiency and
      25(OH)D < 27.5 nmol/L as being indicative of increased risk for rickets.
      Additionally, 25(OH)D > 125 nmol/L was considered possibly adversely high. Total
      vitamin D at 9-12 months (eight data collection days) included intake from diet
      and supplements. The mean +/- SD of vitamin D intake was 8.8 +/- 5.2 MUg/day and
      serum 25(OH)D 98.1 +/- 32.2 nmol/L (range 39.3-165.5). Ninety-two percent of
      infants were vitamin D sufficient and none at increased risk for rickets. The 26%
      infants using fortified products and supplements never/irregularly or in small
      amounts had lower 25(OH)D (76.8 +/- 27.1 nmol/L) than the 22% using fortified
      products (100.0 +/- 31.4 nmol/L), 18% using supplements (104.6 +/- 37.0 nmol/L)
      and 33% using both (110.3 +/- 26.6 nmol/L). Five of six infants with 25(OH)D < 50
      nmol/L had no intake of supplements or fortified products from 0 to 12 months.
      Supplement use increased the odds of 25(OH)D > 125 nmol/L. Breastfeeding and
      season did not affect vitamin D status. The majority of infants were vitamin D
      sufficient. Our findings highlight the need for vitamin D supplements or
      fortified products all year round, regardless of breastfeeding. 

PMID- 24662163
TI  - Curcumin protects against cadmium-induced vascular dysfunction, hypertension and
      tissue cadmium accumulation in mice.
AB  - Curcumin from turmeric is commonly used worldwide as a spice and has been
      demonstrated to possess various biological activities. This study investigated
      the protective effect of curcumin on a mouse model of cadmium (Cd)-induced
      hypertension, vascular dysfunction and oxidative stress. Male ICR mice were
      exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100
      mg/kg) was intragastrically administered in mice every other day concurrently
      with Cd. Cd induced hypertension and impaired vascular responses to
      phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic
      effects of Cd and protected vascular dysfunction by increasing vascular
      responsiveness and normalizing the blood pressure levels. The vascular protective
      effect of curcumin in Cd exposed mice is associated with up-regulation of
      endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione
      redox ratio and alleviation of oxidative stress as indicated by decreasing
      superoxide production in the aortic tissues and reducing plasma malondialdehyde,
      plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also
      decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice.
      These findings suggest that curcumin, due to its antioxidant and chelating
      properties, is a promising protective agent against hypertension and vascular
      dysfunction induced by Cd. 

PMID- 24662164
TI  - Vitamin A/retinol and maintenance of pluripotency of stem cells.
AB  - Retinol, the alcohol form of vitamin A is a key dietary component that plays a
      critical role in vertebrate development, cell differentiation, reproduction,
      vision and immune system. Natural and synthetic analogs of retinol, called
      retinoids, have generally been associated with the cell differentiation via
      retinoic acid which is the most potent metabolite of retinol. However, a direct
      function of retinol has not been fully investigated. New evidence has now emerged
      that retinol supports the self-renewal of stem cells including embryonic stem
      cells (ESCs), germ line stem cells (GSCs) and cancer stem cells (CSCs) by
      activating the endogenous machinery for self-renewal by a retinoic acid
      independent mechanism. The studies have also revealed that stem cells do not
      contain enzymes that are responsible for metabolizing retinol into retinoic acid.
      This new function of retinol may have important implications for stem cell
      biology which can be exploited for quantitative production of pure population of
      pluripotent stem cells for regenerative medicine as well as clinical applications
      for cancer therapeutics. 

PMID- 24662165
TI  - UK Renal Registry 16th annual report: chapter 1 UK renal replacement therapy
      incidence in 2012: national and centre-specific analyses.
AB  - INTRODUCTION: This chapter describes the characteristics of adult patients
      starting renal replacement therapy (RRT: kidney dialysis or a kidney transplant)
      in the UK in 2012 and the incidence rates for RRT in Primary Care Trusts and
      Health Boards (PCT/HBs) in the UK. METHODS: Basic demographic and clinical
      characteristics are reported on patients starting RRT at all UK renal centres.
      Presentation time, defined as time between first being seen by a nephrologist and
      start of RRT, was also studied. Age and gender standardised ratios for incidence
      rates in PCT/HBs were also calculated. RESULTS: In 2012, RRT was initiated in
      6,891 patients across the UK, an incidence rate similar to 2011 at 108 per
      million population (pmp). There were wide variations between PCT/HBs in
      standardised incidence ratios. The median age for Whites was 66.1 and for non
      Whites 57.8 years. Diabetic renal disease remained the single most common cause
      of renal failure (26%). By 90 days, 66.9% of patients were on haemodialysis (HD),
      19.0% on peritoneal dialysis (PD), 8.3% had had a transplant and 5.9% had died or
      stopped treatment. There was variability between centres in the use of PD as an
      initial treatment (3-48%). The mean eGFR at the start of RRT was 8.5 ml/min/1.73
      m(2) similar to previous years. Late presentation (<90 days) fell from 23.9% in
      2006 to 19.3% in 2012. Fifty-three percent of patients who started on HD had died
      within five years of starting. This compared to 30% and 4% for those starting on
      PD or transplant respectively. CONCLUSIONS: The incidence of new patients
      starting renal replacement therapy in the UK has remained unchanged for almost 10
      years in contrast to the rising prevalence. The year on year increase in pre
      emptive transplantation is encouraging but the variability between centres in the
      percentages starting on PD should be explored further.

PMID- 24662166
TI  - UK Renal Registry 16th annual report: chapter 2 UK RRT prevalence in 2012:
      national and centre-specific analyses.
AB  - INTRODUCTION: This chapter describes the characteristics of adult patients on
      renal replacement therapy (RRT) in the UK in 2012. METHODS: Data were
      electronically collected from all 71 renal centres within the UK. A series of
      crosssectional and longitudinal analyses were performed to describe the
      demographics of prevalent RRT patients in 2012 at centre and national level.
      RESULTS: There were 54,824 adult patients receiving RRT in the UK on 31st
      December 2012. The UK adult prevalence of RRT was 861 pmp. This represented an
      annual increase in absolute prevalent numbers of approximately 3.7%, although
      there was variation between centres and Primary Care and Health Board areas. The
      actual number of patients increased across all modalities: 2.3% haemodialysis
      (HD), 0.3% peritoneal dialysis (PD) and 5.6% for those with a functioning
      transplant. The number of patients receiving home HD has increased by 19.3% since
      2011. Median RRT vintage for patients on HD was 3.4 years, PD 1.7 years and for
      those patients with a transplant, 10.2 years. The median age of prevalent
      patients was 58 years (HD 66 years, PD 63 years, transplant 52 years) compared to
      55 years in 2005. For all ages the prevalence rate in men exceeded that in women.
      The most common recorded renal diagnosis was glomerulonephritis (biopsy
      proven/not biopsy proven) (18.8%). Transplantation was the most common treatment
      modality (50.4%) CONCLUSIONS: The HD and transplant population continued to
      expand; the decline in the size of the prevalent PD population has plateaued.
      There were national, regional and dialysis centre level variations in prevalence
      rates. Prevalent patients were on average three years older than the prevalent
      RRT cohort 7 years ago. This has continued implications for service planning and
      ensuring equity of care for RRT patients.

PMID- 24662167
TI  - UK Renal Registry 16th annual report: chapter 3 demographic and biochemistry
      profile of kidney transplant recipients in the UK in 2012: national and centre
      specific analyses.
AB  - INTRODUCTION: National transplant registries routinely focus on centre-specific
      patient and graft survival rates following renal transplantation. However other
      outcomes such as graft function (as measured by eGFR), haemoglobin and blood
      pressure are also important quality of care indicators. METHODS: Renal transplant
      activity, incident graft survival data and donor information were obtained from
      NHS Blood and Transplant. Laboratory and clinical variables and prevalent
      survival data were obtained from the UK Renal Registry. Data were analysed
      separately for prevalent and one year post-transplant patients. RESULTS: The main
      increase in transplant activity in 2012 was the use of donors after circulatory
      death. The death-censored graft failure rate was similar to previous years at
      2.2% and the transplant patient death rates remained stable at 2.3 per 100
      patient years. There was centre variation in outcomes including eGFR and
      haemoglobin in prevalent and 1 year posttransplant patients. Analysis of
      prevalent transplants by chronic kidney disease stage showed 13.7% with an eGFR
      <30 ml/min/1.73 m(2) and 1.7% with an eGFR <15 ml/min/1.73 m(2). Of those with
      CKD stage 5T, 33% had haemoglobin concentrations <100 g/L, 27.6% phosphate
      concentrations 1.7 mmol/L and 20.5% adjusted calcium concentrations 2.5 mmol/L.
      Infection (23%) and malignancy (20%) remained amongst the commonest causes of
      death in patients with a functioning renal transplant. CONCLUSIONS: Significant
      variations in clinical outcomes (unadjusted for patient specific variables)
      amongst kidney transplant recipients continued to exist in the UK and may reflect
      differences in healthcare delivery between renal centres.

PMID- 24662168
TI  - UK Renal Registry 16th annual report: chapter 4 demography of patients waitlisted
      for renal transplantation in the UK: national and centre-specific analyses.
AB  - INTRODUCTION: For suitable patients, renal transplantation is considered the
      optimal modality of renal replacement therapy, with availability of donor organs
      limiting the number of transplants undertaken. The 2006 kidney allocation policy
      was developed to ensure equity of allocation to patients on the transplant
      waiting list, whilst still achieving a good donor/recipient match. This study
      aims to describe the characteristics of the kidney transplant waiting list and
      variations in median waiting times. METHODS: Demographics and clinical
      characteristics of all patients listed for a kidney only transplant in the UK on
      1st January 2011 were examined. Renal unit variations were explored. Patients
      listed between January 2006 and December 2009 were included in analysis of
      waiting times to transplant. RESULTS: At the beginning of 2011, there were 6,699
      patients registered active for kidney only transplant in UK; a prevalence rate of
      107 pmp. The median age of prevalent listed patients was 53 years, with 8% aged
      70 or above. Of the patients listed, 84% had started renal replacement therapy
      (RRT), 59% were male, 28% were from ethnic minorities, 50% had blood group type
      O, 28% were defined as difficult to HLA match and 23% were highly sensitised
      (calculated HLA antibody reaction frequency 85%). Median waiting time to
      transplant was 38 months. Waiting time was shorter for White patients (36 months)
      compared to Asian or Black patients (46 months), and was doubled in highly
      sensitised compared to un-sensitised patients. CONCLUSIONS: Intercentre variation
      was observed in the rate of wait-listing and in the proportion of listed patients
      across different ethnic groups, age, blood groups and level of sensitisation.
      This may reflect differences in baseline population characteristics as well as
      individual centre practice patterns. Median waiting times differ significantly
      across blood groups, degree of sensitisation and ethnic group.

PMID- 24662169
TI  - UK Renal Registry 16th annual report: chapter 5 comorbidities and current smoking
      status amongst patients starting renal replacement therapy in England, Wales and
      Northern Ireland from 2011 to 2012.
AB  - INTRODUCTION: Comorbidities are significant predictors of mortality and other
      adverse outcomes. Case-mix adjustment is integral to quality reporting, risk
      adjustment in clinical research, resource allocation and management of patients
      with comorbid conditions in day to day practice such as dialysis access formation
      and transplant wait-listing. This study describes the comorbidity data submitted
      to the UK Renal Registry (UKRR) in incident renal replacement therapy (RRT)
      patients and examines the association between these comorbidities and early
      mortality. METHODS: Incident patients reported to the UKRR with comorbidity data
      in 2011 and 2012 (n = 7,085) were included in analyses exploring the association
      of comorbidities with patient demographics and treatment modality. For analyses
      examining the association between comorbidities and survival, adult patients
      starting RRT between 2007 and 2012 in centres reporting to the UKRR with
      comorbidity data were included. The relationship between comorbidities and
      mortality at 90 days and one year after 90 days from start of RRT were explored
      using Cox regression. RESULTS: Completeness of comorbidity data was 55% in 2012
      compared with 56% in 2007. Of patients with data, 52.9% had one or more
      comorbidities. Diabetes mellitus and ischaemic heart disease were the most common
      conditions, observed in 35% and 19% of patients respectively. Fourteen percent of
      incident RRT patients in the 2-year period were recorded as current smokers. The
      prevalence of comorbidity increased with increasing age across all ethnic groups.
      In multivariable survival analysis, malignancy and liver disease were strong
      independent predictors of poor survival at 1-year after 90 days from the start of
      RRT in patients <65 years. CONCLUSIONS: Continuing efforts from renal centres to
      improve data capture in addition to the use of data linkage and statistical
      techniques such as multiple imputation by the UKRR are likely to lead to enhanced
      case mix adjustment in the future.

PMID- 24662170
TI  - UK Renal Registry 16th annual report: chapter 6 demographics and outcomes of
      patients from different ethnic groups on renal replacement therapy in the UK.
AB  - INTRODUCTION: This chapter describes the patient characteristics and outcomes for
      the three main ethnic groups (White, South Asian, Black) on renal replacement
      therapy (RRT) in the UK. METHODS: Data on patients (>18 years old) from all 71 UK
      adult renal centres starting RRT between 2003 and 2012 were considered. Scottish
      centres were excluded due to poor ethnicity data. RESULTS: The age-gender
      standardized incidence ratio of RRT was higher (2-3 times) in regions with a high
      ethnic minority population compared to those with a low ethnic minority
      population. South Asian and Black patients were significantly younger than
      Whites; had more diabetes causing established renal failure and lived in more
      deprived areas. The proportion of patients with at least one comorbidity was
      greater amongst White patients compared to South Asian and Black patients. The
      proportion of patients starting PD and having preemptive transplantation was
      lower amongst both ethnic minorities. The attainment of various laboratory
      standards was comparable or better for the ethnic minorities compared to White
      patients except for calcium standard attainment (for South Asians) and
      haemodialysis dose attainment (for Black patients). Compared to White patients,
      both ethnic minorities had similar rates of listing for deceased donor kidney
      transplantation but had lower rates of transplantation once wait-listed, and
      lower rates of living kidney donor transplantation. One and five year kidney
      allograft adjusted survival was poorer for Black patients but similar for South
      Asians compared to White patients. Black and South Asian patients had a better
      adjusted survival on dialysis compared to White patients. CONCLUSIONS: The
      persistent high incidence of RRT, the better survival on dialysis and the poor
      access to kidney transplantation for South Asian and Black patients and early
      allograft loss for Black patients will impose a disproportionate demand on
      dialysis provision in those areas with a high ethnic minority population.

PMID- 24662171
TI  - UK Renal Registry 16th annual report: chapter 7 demography of the UK paediatric
      renal replacement therapy population in 2012.
AB  - INTRODUCTION: To describe the demographics of the paediatric renal replacement
      therapy (RRT) population under the age of 18 years in the UK and to analyse
      changes in demography with time. METHODS: Data were collected from all 13
      paediatric renal centres within the UK. A series of crosssectional and
      longitudinal analyses were performed to describe the demographics of paediatric
      RRT patients. RESULTS: A total of 861 children and young people under 18 with
      established renal failure (ERF) were receiving treatment at paediatric nephrology
      centres in 2012. At the census date, 80.2% had a functioning transplant, 10.6%
      were receiving haemodialysis (HD) and 9.2% were receiving peritoneal dialysis
      (PD). In patients aged <16 years the prevalence of ERF was 56.7 pmarp and the
      incidence 9.0 pmarp. A third of the prevalent patients had one or more reported
      comorbidities. At transfer to adult services, 81.5% of patients had a functioning
      renal transplant. Preemptive transplantation was seen to occur in a third of
      children starting RRT under 16 years, with lower rates seen in girls and ethnic
      minorities. Over the past 15 years for those referred early, there has been a
      rise in pre-emptive transplantation rates, rising from 26.2% in 1998-2002 to
      36.3% in 2008-2012. Over the same period there has also been an increase in
      living donation from 7.1% to 18%. Survival in childhood amongst children starting
      RRT was the lowest in those aged less than two years. CONCLUSIONS: The findings
      of this report are similar to last year with continued improvement in data
      quality and electronic submission of data returns. The data provided in this
      report show slowly increasing trends of incidence and prevalence in children with
      established renal failure.

PMID- 24662172
TI  - UK Renal Registry 16th annual report: chapter 8 survival and cause of death of UK
      adult patients on renal replacement therapy in 2012: national and centre-specific
      analyses.
AB  - INTRODUCTION: These analyses examine: a) survival from the start of renal
      replacement therapy (RRT); b) survival amongst all prevalent dialysis patients
      alive on 31st December 2011; c) the cause of death for incident and prevalent
      patients and d) the projected life years remaining for patients starting RRT.
      Changes in survival between the 1997 and 2011 cohort are also reported. METHODS:
      Survival was calculated for both incident and prevalent patients on RRT. Survival
      of incident patients (starting RRT during 2011) was calculated both from the
      start of RRT and from 90 days after starting RRT, both with and without censoring
      at transplantation. Prevalent dialysis patients were censored at transplantation.
      Both Kaplan-Meier and Cox adjusted models were used to calculate survival. The
      relative risk of death was calculated and compared with the UK general
      population. RESULTS: The unadjusted 1 year after 90 day survival for patients
      starting RRT in 2011 was 87.5%, representing an increase from the previous year
      (87.3%). The age-adjusted one year survival (adjusted to age 60) of prevalent
      dialysis patients increased from 88.2% in the 2002 cohort to 89.7% in the 2011
      cohort. Prevalent diabetic patient one year survival rose from 81.6% in the 2002
      cohort to 84.9% in the 2011 cohort. The age-standardised mortality ratio for
      prevalent RRT patients compared with the general population was 16.6 for age
      group 35-39 and 2.7 at age 85+ years. In the prevalent RRT dialysis population,
      cardiovascular disease accounted for 22% of deaths, infection 17% and treatment
      withdrawal 19%. The median life years remaining for a 25-29 year old on RRT was
      18.5 years and approximately 2.5 for a 75+ year old. CONCLUSIONS: Survival of
      patients starting RRT has improved in the 2011 incident cohort. The relative risk
      of death on RRT compared with the general population has fallen since 2001.

PMID- 24662173
TI  - UK Renal Registry 16th annual report: chapter 9 adequacy of haemodialysis in UK
      adult patients in 2012: national and centre-specific analyses.
AB  - INTRODUCTION: Outcomes in patients treated with haemodialysis (HD) are influenced
      by the delivered dose of dialysis. The UK Renal Association (RA) publishes
      clinical practice guidelines which include recommendations for dialysis dose. The
      urea reduction ratio (URR) is a widely used measure of dialysis dose and has
      historically been the measure of adequacy reported by the UKRR. This chapter aims
      to determine the extent to which patients achieved the recommended UK target.
      METHODS: All 71 UK renal centres submitted data to the UK Renal Registry (UKRR).
      Two groups of patients were included in the analyses: the prevalent HD patient
      population on 30st September 2012 and the incident HD patient population for
      2011. Centres returning data on <50% of their patient population or centres with
      <20 patients were excluded from centrespecific comparisons. RESULTS: Data
      regarding URR were available from 63 renal centres in the UK. Forty nine centres
      provided URR data on more than 90% of prevalent HD patients. The proportion of
      patients in the UK who met the UK clinical practice guideline for URR (>65%)
      increased from 69% in 2000 to 88% in 2012. There was persistent variation
      observed between centres, with 21 centres attaining the RA clinical practice
      guideline in >90% of patients, 38 centres attaining the guideline in 70-90% of
      patients and one centre in less than 70% of patients. The overall proportion of
      prevalent HD patients with a URR >65% has continued to improve over time.
      CONCLUSIONS: The delivered dose of HD, as measured by URR for patients with
      established renal failure, has increased over the last decade. Whilst the
      majority of UK patients achieved the target URR there was considerable variation
      between centres in the percentage of patients achieving the current guideline.

PMID- 24662174
TI  - UK Renal Registry 16th annual report: chapter 10 haemoglobin, ferritin and
      erythropoietin amongst UK adult dialysis patients in 2012: national and centre
      specific analyses.
AB  - INTRODUCTION: Anaemia treatment in chronic kidney disease (CKD) patients has
      changed dramatically since the implementation of erythropoietin stimulating
      agents (ESAs) and has shifted the emphasis from treating severe anaemia in
      dialysis patients to preventing anaemia. The aim of this chapter is to determine
      the extent to which the UK Renal Association (RA) and National Institute for
      Health and Care Excellence (NICE) guidelines for anaemia management are met in
      the UK. METHODS: Quarterly data were obtained for haemoglobin (Hb) and factors
      that influence Hb from UK renal centres for the incident and prevalent renal
      replacement therapy (RRT) cohorts for 2012. RESULTS: In the UK, in 2012, 51% of
      patients commenced dialysis therapy with Hb 100 g/L (median Hb 100 g/L). Of
      patients in the early presentation group, 54% started dialysis with Hb 100 g/L
      whilst 34% of patients presenting late started dialysis with Hb 100 g/L. The UK
      median Hb of haemodialysis (HD) patients was 112 g/L, with 82% of patients having
      Hb 100 g/L. The median Hb of peritoneal dialysis (PD) patients in the UK was 114
      g/L, with 85% of patients having Hb 100 g/L. The median ferritin in HD patients
      in the UK was 431 ug/L and 95% of HD patients had a ferritin 100 ug/L. In EW&NI
      the median ferritin in PD patients was 285 ug/L (IQR 164-466) with 88% of PD
      patients having a ferritin 100 ug/L. In EW&NI the median ESA dose was higher for
      HD than PD patients (7,248 vs. 4,250 IU/week). The percentage of patients treated
      with an ESA and having Hb >120 g/L ranged between centres from 7-39% for HD and
      from 0-33% for PD. CONCLUSIONS: There was poor correlation between median Hb
      achieved and median ferritin and ESA usage across the EW&NI centres. There was
      also a significant variation between centres in the percentages of patients
      treated with an ESA and having Hb >120 g/L. (c) 2014 S. Karger AG, Basel.

PMID- 24662175
TI  - UK Renal Registry 16th annual report: chapter 11 blood pressure profile of
      prevalent patients receiving renal replacement therapy in 2012: national and
      centre-specific analyses.
AB  - INTRODUCTION: There continues to be uncertainty in the literature about which
      blood pressure (BP) recordings in which time period associate best with long-term
      patient outcomes and therefore optimal target ranges. METHODS: Patients receiving
      renal replacement therapy (RRT) on 31st December 2012 with a BP reading in either
      the fourth or third quarter of 2012 were included. Summary statistics were
      calculated for each renal centre and country. RESULTS: Data completeness for BP
      measurements submitted to the UK Renal Registry (UKRR) for all modalities were
      improved from previous years: it was better for haemodialysis (HD) patients (75%
      for pre-HD measurements) than for peritoneal dialysis (PD) patients (51%) or
      transplant recipients (41%). In 2012, the median pre- and post-HD systolic blood
      pressures (SBPs) were 140 mmHg and 128 mmHg respectively. The median SBP of
      patients on PD was 137 mmHg. Transplant recipients had a median SBP of 134 mmHg.
      Median diastolic blood pressures (DBPs) were 71 mmHg (pre-HD), 67 mmHg (post-HD),
      78 mmHg (PD) and 79 mmHg (transplant). Only 26% of PD patients achieved the Renal
      Association guideline of SBP <130 mmHg and DBP <80 mmHg. Amongst transplant
      patients, 27% achieved the Renal Association guideline of SBP <130 mmHg and DBP
      <80 mmHg. CONCLUSION: In 2012 there continued to be significant variation in the
      achievement of BP standards between UK renal centres.

PMID- 24662176
TI  - UK Renal Registry 16th annual report: chapter 12 biochemical variables amongst UK
      adult dialysis patients in 2012: national and centre-specific analyses.
AB  - INTRODUCTION: The UK Renal Association clinical practice guidelines include
      clinical performance measures for biochemical variables in dialysis patients. The
      UK Renal Registry (UKRR) annually audits dialysis centre performance against
      these measures as part of its role in promoting continuous quality improvement.
      METHODS: Cross sectional performance analyses were undertaken to compare dialysis
      centre achievement of clinical audit measures for prevalent haemodialysis (HD)
      and peritoneal dialysis (PD) cohorts in 2012. The biochemical variables studied
      were phosphate, adjusted calcium, parathyroid hormone, bicarbonate and total
      cholesterol. In addition, longitudinal analyses were performed (2002-2012) to
      show changes in achievement of clinical performance measures over time. RESULTS:
      Fifty-six percent of HD and 61% of PD patients achieved a phosphate within the
      range recommended by the RA clinical practice guidelines. Seventy-seven percent
      of HD and 78% of PD patients had adjusted calcium between 2.2-2.5 mmol/L. Fifty
      eight percent of HD and 65% of PD patients had parathyroid hormone between 16-72
      pmol/L. Fifty-nine percent of HD and 80% of PD patients achieved the audit
      measure for bicarbonate. There was significant inter-centre variation for all
      variables studied. CONCLUSIONS: The UKRR consistently demonstrates significant
      inter-centre variation in achievement of biochemical clinical audit measures.
      Understanding the causes of this variation is an important part of improving the
      care of dialysis patients in the UK.

PMID- 24662177
TI  - UK Renal Registry 16th annual report: chapter 13 clinical, haematological and
      biochemical parameters in patients receiving renal replacement therapy in
      paediatric centres in the uk in 2012: national and centre-specific analyses.
AB  - INTRODUCTION: The British Association for Paediatric Nephrology Registry (BAPN)
      was established to analyse data related to renal replacement therapy (RRT) in
      children. The registry receives data from the 13 paediatric nephrology centres in
      the UK. This chapter aims to provide centre specific data so that individual
      centres can reflect on the contribution that their data makes to the national
      picture and to determine the extent to which their patient parameters meet
      nationally agreed audit standards for the management of children with established
      renal failure (ERF). METHODS: Data returns included a mixture of electronic (92%)
      and paper (8%) returns. Data were analysed to calculate summary statistics and
      where applicable the percentage achieving an audit standard. The standards used
      were those set out by the Renal Association and the National Institute for Health
      and Clinical Excellence. RESULTS: Anthropometric data confirmed that children
      receiving RRT were short compared to healthy peers. Amongst patients with a
      height of <2SD between 2001 and 2012, 29.2%were receiving growth hormone if they
      were on dialysis compared to 11.9% if they had a functioning transplant.
      Prevalence rates of overweight and obese status in children with ERF remain
      concerningly high. Blood pressure control remained challenging with wide inter
      centre variation although this was significantly better in children with a
      functioning transplant. Over a quarter of haemodialysis patients and 17.3% of
      peritoneal dialysis patients were anaemic, compared to only 8.3% of transplanted
      patients. ESA use in the dialysis population exceeded 90% amongst anaemic
      patients. The control of renal bone disease remained challenging. CONCLUSIONS:
      Optimising growth and reducing prevalent excess weight in children on RRT remains
      challenging. The likelihood of complete electronic reporting in the near future
      with plans for quarterly reporting in the format of the recently finalised NEW
      paediatric dataset will hopefully improve quality of data and their reporting,
      allowing improvements in patient care.

PMID- 24662178
TI  - UK Renal Registry 16th annual report: chapter 14 2012 multisite dialysis access
      audit in England, Northern Ireland and Wales and 2011 PD one year follow-up:
      national and centre-specific analyses.
AB  - INTRODUCTION: Dialysis access should be timely, minimise complications and
      maintain functionality. Good functional access is required for renal replacement
      therapy (RRT) to be successful. The aim of the combined vascular and peritoneal
      dialysis access audit was to examine practice patterns with respect to dialysis
      access and highlight variations in practice between renal centres. METHODS: The
      UK Renal Registry collected centre-specific information on vascular and
      peritoneal access outcome measures including patient demographics, dialysis
      access type (at start of dialysis and three months after start of dialysis),
      surgical assessment and access functionality. The combined access audit covered
      incident haemodialysis (HD) and peritoneal dialysis (PD) patients in 2012 from
      England, Northern Ireland and Wales. Centres who had reported data on incident PD
      patients for the previous audit in 2011 were additionally asked to provide one
      year follow up data for this group. RESULTS: Fifty-one centres in England, Wales
      and Northern Ireland (representing 82% of all centres) returned data on first
      access from 3,720 incident HD patients and 1,018 incident PD patients. A strong
      relationship was seen between surgical assessment and the likelihood of starting
      HD with an arteriovenous fistula (AVF). Type of first access was related to the
      length of time known to renal services with higher numbers of AVFs and PD
      catheters used in patients known to renal services for at least one year. Three
      month and one year outcomes of HD and PD access were poorly reported.
      CONCLUSIONS: This audit provides information on important patient related outcome
      measures with the potential to lead to an improvement in access provision. This
      represents an important advance, however data collection remains suboptimal.
      There is wide practice variation across the England, Wales and Northern Ireland
      in provision of both HD and PD access which requires further exploration.

PMID- 24662179
TI  - UK Renal Registry 16th annual report: chapter 15 epidemiology of reported
      infections amongst patients receiving dialysis for established renal Failure in
      England from May 2011 to April 2012: a joint report from Public Health England
      and the UK renal registry.
AB  - INTRODUCTION: Infection remains one of the leading causes of mortality in
      established renal failure patients receiving renal replacement therapy (RRT).
      Since 2007, centres providing RRT in England have been asked to provide
      additional data on patients with methicillin resistant Staphylococcus aureus
      (MRSA) bacteraemia. Since 2011, the option to provide data on methicillin
      sensitive Stapylococcus aureus (MSSA) and Escherichia coli bacteraemia, as well
      as Clostridium difficile infection has also been available. METHODS: Data were
      submitted to Public Health England by laboratories via HCAI-DCS including whether
      the patients were receiving dialysis. Individual renal centres then confirmed the
      record either directly via the database or after being contacted. Data were
      collected for the period of the 1st May 2011 to the 30th April 2012. RESULTS:
      There were 49 episodes of MRSA bacteraemia, an overall rate of 0.22 per 100
      dialysis patients per year, representing a further year on year fall in MRSA
      rate. There were a higher number of MSSA episodes, 322 in total, with an overall
      rate of 1.15 per 100 dialysis patients per year. The number of episodes and
      overall rate of E. coli and C. difficile were 284 and 0.92 per 100 prevalent
      dialysis patients per year and 172 and 0.61 per 100 prevalent dialysis patients
      per year respectively. In each infection type the presence of a central venous
      catheter appeared to correlate with an elevated risk. CONCLUSIONS: Data are
      presented from one year of infections reported to PHE. The rate of MRSA
      bacteraemia episodes in England continues to fall. There was a higher rate of
      MSSA infections amongst renal dialysis patients. Findings from the first year of
      E. coli and C. difficile data collection are also reported. Future cycles will
      give us a further idea of the trend in incidences of these infections.

PMID- 24662180
TI  - UK Renal Registry 16th annual report: Appendices.

PMID- 24662191
TI  - Reprint of: Musculoskeletal system in the old age and the demand for healthy
      ageing biomarkers.
AB  - Population ageing has emerged as a major demographic trend worldwide due to
      improved health and longevity. This global ageing phenomenon will have a major
      impact on health-care systems worldwide due to increased morbidity and greater
      needs for hospitalization/institutionalization. As the ageing population
      increases worldwide, there is an increasing awareness not only of increased
      longevity but also of the importance of "healthy ageing" and "quality of life".
      Yet, the age related chronic inflammation is believed to be pathogenic with
      regards to its contribution to frailty and degenerative disorders. In particular,
      the frailty syndrome is increasingly being considered as a key risk indicator of
      adverse health outcomes. In addition, elderly may be also prone to be resistant
      to anabolic stimuli which is likely a key factor in the loss of skeletal muscle
      mass with ageing. Vital to understand these key biological processes is the
      development of biological markers, through system biology approaches, aiding at
      strategies for tailored therapeutic and personalized nutritional program. Overall
      aim is to prevent or attenuate decline of key physiological functions required to
      live an active, independent life. This review focus on core indicators of health
      and functions in older adults, where nutrition and tailored personalized programs
      could exhibit preventive roles, and where the aid of metabolomics technologies
      are increasingly displaying potential in revealing key molecular
      mechanisms/targets linked to specific ageing and/or healthy ageing processes. 

PMID- 24662192
TI  - Motor and cognitive advantages persist 12 months after exenatide exposure in
      Parkinson's disease.
AB  - BACKGROUND: Data from an open label randomised controlled trial have suggested
      possible advantages on both motor and non-motor measures in patients with
      Parkinson's disease following 12 months exposure to exenatide. OBJECTIVE:
      Continued follow up of these same patients was performed to investigate whether
      these possible advantages persisted in the prolonged absence of this medication.
      METHODS: All participants from an open label, randomised controlled trial of
      exenatide as a treatment for Parkinson's disease, were invited for a further
      follow up assessment at the UCL Institute of Neurology. This visit included all
      20 individuals who had previously completed twelve months exposure to exenatide
      10ug bd and the 24 individuals who had acted as randomised controls. Motor
      severity of PD was compared after overnight withdrawal of conventional PD
      medication using blinded video assessment of the MDS-UPDRS, together with several
      non-motor tests. This assessment was thus 24 months after their original baseline
      visit, i.e. 12 months after cessation of exenatide. RESULTS: Compared to the
      control group of patients, patients previously exposed to exenatide had an
      advantage of 5.6 points (95% CI, 2.2-9.0; p = 0.002) using blinded video rating
      of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3
      points; (95% CI, 9.3-1.4; p = 0.006) between the 2 groups on the Mattis Dementia
      Rating scale. CONCLUSIONS: While these data must still not be interpreted as
      evidence of neuroprotection, they nevertheless provide strong encouragement for
      the further study of this drug as a potential disease modifying agent in
      Parkinson's disease.

PMID- 24662193
TI  - Resting state functional connectivity is associated with cognitive dysfunction in
      non-demented people with Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) can result in cognitive impairment.
      Executive dysfunction often appears early, followed by more widespread deficits
      later in the course of the disease. Disruption of parallel basal ganglia thalamo
      cortical loops that subserve motor and cognitive function has been described in
      PD. However, there is emerging evidence that the default mode network, a cortical
      network that is active at rest with reduced activation during task performance,
      may also play a role in disease related cognitive decline. OBJECTIVE: To
      determine the relative contribution of the executive control and default mode
      networks to parkinsonian executive dysfunction in medicated non-demented
      patients. METHODS: We used BOLD fMRI to measure resting state functional
      connectivity in the executive control and default mode (DM) networks, and
      examined switching, processing speed, working memory/attention and motor
      performance in 14 medicated non-demented PD participants and 20 controls.
      RESULTS: Performance on neuropsychological measures was similar across groups.
      Functional connectivity was not different across disease conditions in the
      executive control network. DMN functional connectivity was decreased in the PD
      group, specifically between posterior cingulate, medial prefrontal, and inferior
      parietal nodes. Greater DMN functional connectivity was associated with faster
      processing speed in the PD group. CONCLUSIONS: The continuous relationship
      between DMN disconnection and executive task performance indicates a possible
      biological contributor to parkinsonian cognitive deficits. The dynamics of
      executive control network change may be different than that of the DMN,
      suggesting less sensitivity to early cognitive deficits.

PMID- 24662194
TI  - Nine-year follow-up of children with atopic dermatitis by general practitioners.
AB  - The frequency of associated comorbidity and the cost of treatments in patients
      with atopic dermatitis (AD) followed up in primary care settings are poorly
      known. We carried out a retrospective cohort study on a longitudinal electronic
      medical records database of patients consulting a panel of general practitioners
      in France. All subjects with AD diagnosed during the first year of life were
      selected and matched with infants without the disease according to sex (1,163 vs.
      1,163). Subjects were followed up for 9 years. Associated diseases, drug
      consumptions and available medical costs were detailed. Comparisons between
      subjects and controls were carried out. Subjects with AD had more comorbidities
      than others, especially in respiratory and ophthalmic system organs. The number
      of prescribed treatments in the field of skin diseases as well as overall medical
      costs (general practitioner consultations and prescribed drugs) were higher among
      atopic subjects, but differences were attenuated with age.

PMID- 24662195
TI  - Detection of superoxide production in stimulated and unstimulated living cells
      using new cyclic nitrone spin traps.
AB  - Reactive oxygen species (ROS), including superoxide anion and hydrogen peroxide
      (H2O2), have a diverse array of physiological and pathological effects within
      living cells depending on the extent, timing, and location of their production.
      For measuring ROS production in cells, the ESR spin trapping technique using
      cyclic nitrones distinguishes itself from other methods by its specificity for
      superoxide and hydroxyl radical. However, several drawbacks, such as the low spin
      trapping rate and the spontaneous and cell-enhanced decomposition of the spin
      adducts to ESR-silent products, limit the application of this method to
      biological systems. Recently, new cyclic nitrones bearing a triphenylphosphonium
      (Mito-DIPPMPO) or a permethylated beta-cyclodextrin moiety (CD-DIPPMPO) have been
      synthesized and their spin adducts demonstrated increased stability in buffer. In
      this study, a comparison of the spin trapping efficiency of these new compounds
      with commonly used cyclic nitrone spin traps, i.e., 5,5-dimethyl-1-pyrroline N
      oxide (DMPO), and analogs BMPO, DEPMPO, and DIPPMPO, was performed on RAW 264.7
      macrophages stimulated with phorbol 12-myristate 13-acetate. Our results show
      that Mito-DIPPMPO and CD-DIPPMPO enable a higher detection of superoxide adduct,
      with a low (if any) amount of hydroxyl adduct. CD-DIPPMPO, especially, appears to
      be a superior spin trap for extracellular superoxide detection in living
      macrophages, allowing measurement of superoxide production in unstimulated cells
      for the first time. The main rationale put forward for this extreme sensitivity
      is that the extracellular localization of the spin trap prevents the reduction of
      the spin adducts by ascorbic acid and glutathione within cells. 

PMID- 24662196
TI  - Angiotensin II type 1 receptor blockade suppresses light-induced neural damage in
      the mouse retina.
AB  - Exposure to light contributes to the development and progression of retinal
      degenerative diseases. However, the mechanisms underlying light-induced tissue
      damage are not fully understood. Here, we examined the role of angiotensin II
      type 1 receptor (AT1R) signaling, which is part of the renin-angiotensin system,
      in light-induced retinal damage. Light-exposed Balb/c mice that were treated with
      the AT1R blockers (angiotensin II receptor blockers; ARBs) valsartan, losartan,
      and candesartan before and after the light exposure exhibited attenuated visual
      function impairment, compared to vehicle-treated mice. This effect was dose
      dependent and observed across the ARB class of inhibitors. Further evaluation of
      valsartan showed that it suppressed a number of light-induced retinal effects,
      including thinning of the photoreceptor cell layer caused by apoptosis,
      shortening of the photoreceptor cell outer segment, and increased levels of
      reactive oxygen species (ROS). The role of ROS in retinal pathogenesis was
      investigated further using the antioxidant N-acetyl-l-cysteine (NAC). Treatment
      of light-exposed mice with NAC before the light exposure suppressed the visual
      function impairment and photoreceptor cell histological changes due to apoptosis.
      Moreover, treatment with valsartan or NAC suppressed the induction of c-fos (a
      component of the AP-1 transcription factor) and the upregulation of fasl (a
      proapoptotic molecule whose transcript is regulated downstream of AP-1). Our
      results suggest that AT1R signaling mediates light-induced apoptosis, by
      increasing the levels of ROS and proapoptotic molecules in the retina. Thus, AT1R
      blockade may represent a new therapeutic approach for preventing light-induced
      retinal neural tissue damage. 

PMID- 24662197
TI  - Integrins in periodontal disease.
AB  - Cell surface integrin receptors mediate cell adhesion, migration and cellular
      signaling in all nucleated cells. They are activated by binding to extracellular
      ligands or by intracellular proteins, such as kindlins that engage with their
      cytoplasmic tails. Cells in the periodontal tissues express several integrins
      with overlapping ligand-binding capabilities. A distinct phenotype in the
      periodontium has only been described for knockouts or mutations of three integrin
      subunits, alpha11, beta6 and beta2. Integrin alpha11beta1 appears to have some
      regulatory function in the periodontal ligament of continuously erupting incisors
      in mice. Integrin alphavbeta6 is expressed in the junctional epithelium (JE) of
      the gingiva. Animals deficient in this receptor develop classical signs of
      periodontal disease, including inflammation, apical migration of the JE and bone
      loss, suggesting that it plays a role in the regulation of periodontal
      inflmmation, likely through activation of transforming growth factor-beta1. Lack
      of integrin activation in the JE is also associated with periodontitis. Patients
      with kindlin-1 mutations have severe early-onset periodontal disease. Finally,
      patients with mutations in the leukocyte-specific beta2 integrin subunit have
      severe periodontal problems due to lack of transiting neutrophils in the
      periodontal tissues. 

PMID- 24662198
TI  - Lipid rafts are required for signal transduction by angiotensin II receptor type
      1 in neonatal glomerular mesangial cells.
AB  - Angiotensin II (ANG-II) receptors (AGTRs) contribute to renal physiology and
      pathophysiology, but the underlying mechanisms that regulate AGTR function in
      glomerular mesangium are poorly understood. Here, we show that AGTR1 is the
      functional AGTR subtype expressed in neonatal pig glomerular mesangial cells
      (GMCs). Cyclodextrin (CDX)-mediated cholesterol depletion attenuated cell surface
      AGTR1 protein expression and ANG-II-induced intracellular Ca(2+) ([Ca(2+)]i)
      elevation in the cells. The COOH-terminus of porcine AGTR1 contains a caveolin
      (CAV)-binding motif. However, neonatal GMCs express CAV-1, but not CAV-2 and CAV
      3. Colocalization and in situ proximity ligation assay detected an association
      between endogenous AGTR1 and CAV-1 in the cells. A synthetic peptide
      corresponding to the CAV-1 scaffolding domain (CSD) sequence also reduced ANG-II
      induced [Ca(2+)]i elevation in the cells. Real-time imaging of cell growth
      revealed that ANG-II stimulates neonatal GMC proliferation. ANG-II-induced GMC
      growth was attenuated by EMD 66684, an AGTR1 antagonist; BAPTA, a [Ca(2+)]i
      chelator; KN-93, a Ca(2+)/calmodulin-dependent protein kinase II inhibitor; CDX;
      and a CSD peptide, but not PD 123319, a selective AGTR2 antagonist. Collectively,
      our data demonstrate [Ca(2+)]i-dependent proliferative effect of ANG-II and
      highlight a critical role for lipid raft microdomains in AGTR1-mediated signal
      transduction in neonatal GMCs. 

PMID- 24662199
TI  - Expanding the scope of leadership training in medicine.
AB  - All physicians take a leadership role at some point in their career-some exert
      influence in their practices and communities as informal leaders, and others hold
      formal leadership roles to which they are appointed or elected. These formal
      leadership roles convey power to those individuals who hold such positions.
      Formal leadership, however, is limited in its influence unless it is accompanied
      by a series of personal and interpersonal competencies that characterize both
      formal and informal leaders.Many physicians who do not hold formal leadership
      roles will be called on to provide (or will wish to provide) informal leadership
      at various times in their careers. Both formal and informal leaders should be
      trained in the personal and interpersonal competencies necessary for effective
      leadership to advance the principles-driven and values-oriented goals inherent in
      the health care enterprise.In this article, the author defines leadership and
      describes the characteristics of formal and informal leaders, then discusses the
      types of leadership and the power derived from different leadership roles. He
      concludes by arguing in favor of expanding the scope of leadership training to
      include informal as well as formal leaders.

PMID- 24662201
TI  - Evaluating educators using a novel toolbox: applying rigorous criteria flexibly
      across institutions.
AB  - Valuing faculty as educators is essential for medical schools to fulfill their
      unique mission of educating physicians. The 2006 Consensus Conference on
      Educational Scholarship, sponsored by the Association of American Medical
      Colleges (AAMC) Group on Educational Affairs, provided educators seeking academic
      promotion with a portfolio-based format for documenting activities in five
      domains, using evidence of quantity, quality, a scholarly approach, and
      educational scholarship. Yet, the lack of a rigorous, widely accepted system to
      assess educator portfolio submissions during the promotion and tenure process
      continues to impede the ability to fully value educators and educational
      scholars.The AAMC Task Force on Educator Evaluation was formed in 2010 to
      establish consensus guidelines for use by those responsible for the rigorous
      evaluation of the educational contributions of faculty. The task force delineated
      the educational contributions currently valued by institutions and then fulfilled
      its charge by creating the Toolbox for Evaluating Educators, a resource which
      contains explicit evidence-based criteria to evaluate faculty in each of the five
      domains of educator activity. Adoption of such criteria is now the rate-limiting
      step in using a fair process to recognize educators through academic promotion.
      To inform institutional review and implementation of these criteria, this article
      describes the iterative, evidence- and stakeholder-based process to establish the
      criteria. The authors advocate institutional adoption of these criteria so that
      faculty seeking academic promotion as educators, like their researcher
      colleagues, can be judged and valued using established standards for the
      assessment of their work. 

PMID- 24662200
TI  - From competencies to human interests: ways of knowing and understanding in
      medical education.
AB  - When considering the teaching and learning of topics of social relevance in
      medicine, such as professionalism, medical ethics, the doctor-patient
      relationship, and issues of diversity and social justice, one is tempted to ask,
      are the ways of knowing in these fields different from that in the biomedical and
      clinical sciences? Furthermore, given that the competency approach is dominant in
      medical education, one might also ask, is the competency model truly appropriate
      for all of the types of knowledge necessary to become a good physician? These
      questions are not merely academic, for they are at the core of how these subjects
      are taught, learned, and assessed.The goal of this article is threefold: first,
      to explore the nature of knowing and the educational goals in different areas of
      medicine and, in particular, those areas that have social relevance; second, to
      critically review the concept of competencies when applied to education in these
      areas; and third, to explore alternative strategies for teaching, learning, and
      assessment. This discussion reflects a view that the goal of education in areas
      of social relevance in medicine should be the enhancement of an understanding of
      a deep and abiding connection with-the social responsibilities of the physician.
      Moving beyond competencies, this approach aspires toward the development of
      practical wisdom (phronesis) which, when embodied in the physician, links the
      knowledge and skills of the biomedical and clinical sciences with a moral
      orientation and call to action that addresses human interests in the practice of
      medicine. 

PMID- 24662202
TI  - Long term assessment of air quality from a background station on the Malaysian
      Peninsula.
AB  - Rural background stations provide insight into seasonal variations in pollutant
      concentrations and allow for comparisons to be made with stations closer to
      anthropogenic emissions. In Malaysia, the designated background station is
      located in Jerantut, Pahang. A fifteen-year data set focusing on ten major air
      pollutants and four meteorological variables from this station were analysed.
      Diurnal, monthly and yearly pollutant concentrations were derived from hourly
      continuous monitoring data. Statistical methods employed included principal
      component regression (PCR) and sensitivity analysis. Although only one of the
      yearly concentrations of the pollutants studied exceeded national and World
      Health Organisation (WHO) guideline standards, namely PM10, seven of the
      pollutants (NO, NO2, NOx, O3, PM10, THC and CH4) showed a positive upward trend
      over the 15-year period. High concentrations of PM10 were recorded during severe
      haze episodes in this region. Whilst, monthly concentrations of most air
      pollutants, such as: PM10, O3, NOx, NO2, CO and NmHC were recorded at higher
      concentrations between June and September, during the southwest monsoon. Such
      results correspond with the mid-range transport of pollutants from more urbanised
      and industrial areas. Diurnal patterns, rationed between major air pollutants and
      sensitivity analysis, indicate the influence of local traffic emissions on air
      quality at the Jerantut background station. Although the pollutant concentrations
      have not shown a rapid increase, an alternative background station will need to
      be assigned within the next decade if development projects in the surrounding
      area are not halted. 

PMID- 24662203
TI  - Polychlorinated biphenyls in sediments and fish species from the Murchison Bay of
      Lake Victoria, Uganda.
AB  - Polychlorinated biphenyls (PCBs) were determined in sediments and two fish
      species collected from the Murchison Bay in Lake Victoria, using high resolution
      gas chromatography coupled to a high resolution mass spectrometer. Total PCB
      concentrations (Sigma18PCBs) varied widely with mean values ranging from 777 to
      4325pg g(-1) dry weight (dw) for sediments and 80 to 779pg g(-1) wet weight (ww)
      for fish. The PCB levels in the sediments were significantly higher at the
      station closest to Nakivubo channel, presumably due to effluents discharged by
      the channel, which may contain domestically produced commercial PCB mixtures. For
      fish, the concentrations in Nile perch (Lates niloticus) were significantly
      greater than those in Nile tilapia (Oreochromis niloticus) at all study stations,
      possibly due to dietary differences among species. World Health Organization
      toxic equivalents (WHO2005-TEQs) for the dioxin-like PCBs were 0.04-0.64pg g(-1)
      dw and 0.01-0.39pg g(-1) ww for sediments and fish, respectively. The non-ortho
      PCBs exhibited the highest contribution to the Sigma12TEQs (>75%) compared to the
      mono-ortho PCBs in both fish species. The TEQs in the present study were lower
      than many reported worldwide in literature for fish and were within the
      permissible level recommended by the European Commission, implying that the fish
      did not pose health hazards related to PCBs to the consumers.

PMID- 24662204
TI  - Methods for assigning confidence to toxicity data with multiple values-
      Identifying experimental outliers.
AB  - The assessment of data quality is a crucial element in many disciplines such as
      predictive toxicology and risk assessment. Currently, the reliability of toxicity
      data is assessed on the basis of testing information alone (adherence to Good
      Laboratory Practice (GLP), detailed testing protocols, etc.). Common practice is
      to take one toxicity data point per compound - usually the one with the
      apparently highest reliability. All other toxicity data points (for the same
      experiment and compound) from other sources are neglected. To show the benefits
      of incorporating the "less reliable" data, a simple, independent, statistical
      approach to assess data quality and reliability on a mathematical basis was
      developed. A large data set of toxicity values to Aliivibrio fischeri was
      assessed. The data set contained 1813 data points for 1227 different compounds,
      including 203 identified as non-polar narcotic. Log KOW values were calculated
      and non-polar narcosis quantitative structure-activity relationship (QSAR) models
      were built. A statistical approach to data quality assessment, which is based on
      data outlier omission and confidence scoring, improved the linear QSARs. The
      results indicate that a beneficial method for using large data sets containing
      multiple data values per compound and highly variable study data has been
      developed. Furthermore this statistical approach can help to develop novel QSARs
      and support risk assessment by obtaining more reliable values for biological
      endpoints. 

PMID- 24662205
TI  - Urban soil geochemistry in Athens, Greece: The importance of local geology in
      controlling the distribution of potentially harmful trace elements.
AB  - Understanding urban soil geochemistry is a challenging task because of the
      complicated layering of the urban landscape and the profound impact of large
      cities on the chemical dispersion of harmful trace elements. A systematic
      geochemical soil survey was performed across Greater Athens and Piraeus, Greece.
      Surface soil samples (0-10cm) were collected from 238 sampling sites on a regular
      1*1km grid and were digested by a HNO3-HCl-HClO4-HF mixture. A combination of
      multivariate statistics and Geographical Information System approaches was
      applied for discriminating natural from anthropogenic sources using 4 major
      elements, 9 trace metals, and 2 metalloids. Based on these analyses the lack of
      heavy industry in Athens was demonstrated by the influence of geology on the
      local soil chemistry with this accounting for 49% of the variability in the major
      elements, as well as Cr, Ni, Co, and possibly As (median values of 102, 141, 16
      and 24mg kg(-1) respectively). The contribution to soil chemistry of classical
      urban contaminants including Pb, Cu, Zn, Sn, Sb, and Cd (medians of 45, 39, 98,
      3.6, 1.7 and 0.3mg kg(-1) respectively) was also observed; significant
      correlations were identified between concentrations and urbanization indicators,
      including vehicular traffic, urban land use, population density, and timing of
      urbanization. Analysis of soil heterogeneity and spatial variability of soil
      composition in the Greater Athens and Piraeus area provided a representation of
      the extent of anthropogenic modifications on natural element loadings. The
      concentrations of Ni, Cr, and As were relatively high compared to those in other
      cities around the world, and further investigation should characterize and
      evaluate their geochemical reactivity.

PMID- 24662206
TI  - Qualitative environmental risk assessment of photolytic transformation products
      of iodinated X-ray contrast agent diatrizoic acid.
AB  - Recent studies have confirmed that the aquatic ecosystem is being polluted with
      an unknown cocktail of pharmaceuticals, their metabolites and/or their
      transformation products (TPs). Although individual chemicals are typically
      present at low concentrations, they can interact with each other resulting in
      additive or potentially even synergistic mixture effects. Therefore it is
      necessary to assess the environmental risk caused by these chemicals. Data on
      exposure is required for quantitative risk assessment of TPs and/or metabolites.
      Such data are mostly missing because of the non-availability of TPs and very
      often metabolites for experimental testing. This study demonstrates the
      application of different in silico tools for qualitative risk assessment using
      the example of photodegradation TPs (photo-TPs) of diatrizoic acid (DIAT), which
      itself is not readily biodegradable. Its photolytic transformation was studied
      and the photodegradation pathway was established. The aerobic biodegradability of
      photo-TPs under the conditions of an aquatic environment was assessed using
      standardized OECD tests. The qualitative risk assessment of DIAT and selected
      photo-TPs was performed by the PBT approach (i.e. Persistence, Bioaccumulation
      and Toxicity), using experimental biodegradation test assays, applying different
      QSAR models with several different toxicological endpoints and in silico read
      across approaches. The qualitative risk assessment pointed out that the photo-TPs
      were less persistent compared to DIAT and none of them possessed any
      bioaccumulation threat. However, a few photo-TPs were predicted to be active for
      mutagenicity and genotoxicity, which indicate the need for further testing to
      confirm these predictions. The present study demonstrates that in silico
      qualitative risk assessment analysis can increase the knowledge space about the
      environmental fate of TPs. 

PMID- 24662207
TI  - Analysis of hip dysplasia and spinopelvic alignment in cerebral palsy.
AB  - BACKGROUND CONTEXT: Knowledge of sagittal spinopelvic parameters and hip
      dysplasia is important in cerebral palsy (CP) patients because these parameters
      differ from those found in the general population and can be related to symptoms.
      PURPOSE: The purpose of this study was to analyze sagittal spinopelvic alignment
      and determine its relation to hip dysplasia in CP patients. STUDY DESIGN:
      Radiological analysis was conducted on patients with CP. PATIENT SAMPLE: Fifty
      four patients with CP and 24 normal controls were included in this study. OUTCOME
      MEASURES: Participants underwent radiographs of the whole spine. METHODS: The
      patient and control groups comprised 54 CP patients and 24 volunteers,
      respectively. All underwent lateral radiography of the whole spine and hip joint
      anteroposterior radiography. The radiographic parameters examined were sacral
      slope, pelvic tilt, pelvic incidence, S1 overhang, thoracic kyphosis,
      thoracolumbar kyphosis, lumbar lordosis, sagittal balance, center edge angle,
      acetabular angle, and migration index. Statistical analysis was performed to
      identify significant differences and correlations between the two groups.
      RESULTS: Sacral slope, thoracolumbar kyphosis, lumbar lordosis, sagittal balance,
      acetabular angle, and migration index were significantly higher in CP patients,
      whereas pelvic tilt, S1 overhang, and center edge angle were significantly lower
      (p<.05). Correlation analysis revealed that pelvic incidence, sacral slope,
      pelvic tilt, and S1 overhang were related to each other and that thoracolumbar
      kyphosis was related to the thoracic kyphosis and lumbar lordosis (p<.05). For
      spinal and pelvic parameters, lumbar lordosis was related to sacral slope, pelvic
      incidence, pelvic tilt, and S1 overhang; for hip dysplasia parameters, center
      edge angle and acetabular angle were found to be interrelated (p<.05). Regarding
      symptoms, pelvic tilt, S1 overhang, and thoracolumbar kyphosis were found to be
      correlated with symptom severity in patients. However, no hip dysplasia
      parameters were found to be related to hip or spinal symptoms. CONCLUSIONS: This
      study found significant differences between CP patients and normal controls in
      terms of spinopelvic alignment and hip dysplasia. Furthermore, relationships were
      found between the sagittal spinopelvic parameters and hip dysplasia, and
      correlations were found between sagittal spinopelvic parameters and pain.

PMID- 24662208
TI  - Effects of hypoxia on differentiation from human placenta-derived mesenchymal
      stem cells to nucleus pulposus-like cells.
AB  - BACKGROUND CONTEXT: Low back pain is a frequently occurring disease caused by
      intervertebral disc degeneration. Mesenchymal stem cells (MSCs) are a possible
      treatment modality. Studies have shown MSCs can be transformed into nucleus
      pulposus-like cells under normoxic conditions. However, this is not a true
      representation of the hypoxic environment nucleus pulposus cells experience
      during in vivo growth and differentiation. PURPOSE: To determine the effects of a
      hypoxic environment on the differentiation of human placenta-derived mesenchymal
      stem cells (PMSCs) to nucleus pulposus-like cells. STUDY DESIGN: An experimental
      study. METHODS: Placenta-derived mesenchymal stem cells were cultured and the
      mesenchymal lineage was confirmed by flow cytometry. Two groups of PMSCs were
      then cultured under different oxygen concentrations creating a hypoxic group and
      normoxic group. The proliferation of cells in each group was compared by cell
      counting kit-8 on Day 1, 3, 5, and 7. Real-time polymerase chain reaction on Days
      3 and 7 compared the expressions of Sox-9, Type II collagen, aggrecan, and
      hypoxia inducible factor-1alpha (HIF-1alpha) between the two groups.
      Immunofluorescence was used to compare the expression of Type II collagen between
      the two groups after 14 days. RESULTS: Placenta-derived mesenchymal stem cells
      were successfully isolated and cultured. Mesenchymal markers were positive. On
      Days 3 and 5, the hypoxic group had a significantly higher proliferation rate
      than the normoxic group (p<.05). The expression of Sox-9 and HIF-1alpha was
      significantly higher (p<.05) in the hypoxic group at Days 3 and 7. Type II
      collagen and aggrecan expressions were significantly higher (p<.05) in the
      hypoxic group at Day 7. The hypoxic group stained more positive for Type II
      collagen at Day 14. CONCLUSIONS: Hypoxic conditions lead to an increased
      differentiation and proliferation of nucleus pulposus-like cells. Placenta
      derived mesenchymal stem cells cultured in nucleus pulposus inducing media and a
      hypoxic environment show enhanced expression of the nucleus pulposus-like cell
      markers, Sox-9, Type II collagen, aggrecan, and HIF-1alpha.

PMID- 24662209
TI  - Occipitocervical collision after C1-C2 fusion.

PMID- 24662211
TI  - Challenging the norm: further psychometric investigation of the neck disability
      index.
AB  - BACKGROUND CONTEXT: The neck disability index (NDI) was the first patient
      reported outcome (PRO) instrument specific to patients with neck pain, and it
      remains one of the most widely used PROs for the neck population. The NDI is an
      appealing measure as it is a short and well-known PRO measure. Currently, there
      are conflicting data on the performance and applicability of the NDI in patients
      undergoing either operative or nonoperative treatment for neck-related
      conditions. PURPOSE: This study investigates the psychometric properties,
      performance, and applicability of the NDI in the spine patient population. STUDY
      DESIGN: A total of 865 patients visiting a university-based spine clinic with
      neck complaints, with or without radiating upper extremity pain, numbness, or
      weakness were enrolled in the study. Visit types included new and follow-up
      visits to both operative and nonoperative treatments. Questionnaires were
      administered electronically on a tablet computer, and all patients answered all
      10 questions of the NDI. METHODS: Standard descriptive statistics were performed
      to describe the demographic characteristics of the patients. Rasch modeling was
      applied to examine the psychometric properties of the NDI. RESULTS: The NDI
      demonstrated insufficient unidimensionality (ie, unexplained variance after
      accounting for the first dimension=9.4%). Person reliability was 0.85 and item
      reliability was 1.00 for the NDI. The overall item fit for the NDI was good with
      an outfit mean square of 1.03. The NDI had a floor effect of 35.5% and ceiling
      effect of 4.6%. The raw score to measure correlation of the NDI was 0.019.
      CONCLUSIONS: Although the NDI had good person and item reliability, it did not
      demonstrate strong evidence of unidimensionality. The NDI exhibited a very large
      floor effect. Because of the poor raw score to measure correlation, the sum score
      should not be used in interpretation of findings. Despite great investment by
      physicians and other stakeholders in the NDI, this evaluation and previous
      research have demonstrated that the NDI needs further investigation and
      refinement.

PMID- 24662210
TI  - Outcomes are not different for patient-matched versus nonmatched treatment in
      subjects with chronic recurrent low back pain: a randomized clinical trial.
AB  - BACKGROUND CONTEXT: Classification schemas for low back pain (LBP), such as the
      Treatment-Based Classification and the Movement System Impairment, use common
      clinical features to subgroup patients with LBP and are purported to improve
      treatment outcomes. PURPOSE: To assess if providing matched treatments based on
      patient-specific clinical features led to superior treatment outcomes compared
      with an unmatched treatment for subjects with chronic recurrent LBP. STUDY
      DESIGN: This study is a randomized controlled trial. PATIENT SAMPLE: Subjects
      (n=124) with LBP (>=12 months) with or without recurrences underwent a
      standardized clinical examination to group them into one of two strata:
      ineligible or eligible for stabilization exercises based on the Treatment-Based
      Classification schema. Subjects underwent additional clinical tests to assign
      them to one of the five possible Movement System Impairment categories. OUTCOME
      MEASURES: Questionnaires were collected electronically at Week 0 (before
      treatment), Week 7 (after the 6-week 1-hour treatment sessions), and 12 months.
      Using the Oswestry disability index (0-100) and the Numeric Pain Rating Scale (0
      10), the primary analysis was performed using the intention-to-treat principle.
      Secondary outcomes included fear-avoidance beliefs and psychosocial work-related
      and general health status. METHODS: After subjects were categorized based on
      their particular clinical features using both the Treatment-Based Classification
      and Movement System Impairment schemas, they were randomized into one of two
      treatments using a 3:1 ratio for matched or unmatched treatments. The treatments
      were trunk stabilization exercise or Movement System Impairment-directed
      exercises. RESULTS: Of the patients allocated to treatment for this study, 76
      received a matched treatment and 25 received an unmatched treatment. After
      treatment, both groups showed a statistically significant improvement in the
      primary outcome measures and almost all the secondary measures; however, the
      matched treatment group did not demonstrate superior outcomes at Week 7 or 12
      months, except on one of the secondary measures (Graded Chronic Pain Scale
      [Disability Scale]) (p=.01). CONCLUSIONS: Providing a matched treatment based on
      either the Treatment-Based Classification or the Movement System Impairment
      classification schema did not improve treatment outcomes compared with an
      unmatched treatment for patients with chronic LBP, except on one secondary
      disability measure.

PMID- 24662212
TI  - The syrinx cavity with cranial extension in an adult patient with Chiari Type 1
      malformation.

PMID- 24662214
TI  - Influence of severe kyphosis.

PMID- 24662213
TI  - Dysphagia after anterior cervical spine surgery: a systematic review of potential
      preventative measures.
AB  - BACKGROUND CONTEXT: Anterior cervical spine surgery is one of the most common
      spinal procedures performed around the world, but dysphagia is a frequent
      postoperative complication. Many factors have been associated with an increased
      risk of swallowing difficulties, including multilevel surgery, revision surgery,
      and female gender. PURPOSE: The objective of this study was to review and define
      potential preventative measures that can decrease the incidence of dysphagia
      after anterior cervical spine surgery. STUDY DESIGN: This was a systematic
      literature review. METHODS: A systematic review in the Medline database was
      performed. Articles related to dysphagia after anterior cervical spine surgery
      and potential preventative measures were included. RESULTS: Twenty articles met
      all inclusion and exclusion criteria. These articles reported several potential
      preventative measures to avoid postoperative dysphagia. Preoperative measures
      include performing tracheal exercises before the surgical procedure.
      Intraoperative measures can be summarized as avoiding a prolonged operative time
      and the use of recombinant human bone morphogenetic protein in routine anterior
      cervical spine surgery, using small and smoother cervical plates, using anchored
      spacers instead of plates, application of steroid before wound closure,
      performing arthroplasty instead of anterior cervical fusion for one-level
      disease, decreasing tracheal cuff pressure during medial retraction, using
      specific retractors, and changing the dissection plan. CONCLUSIONS: Current
      literature supports several preventative measures that may decrease the incidence
      of postoperative dysphagia. Although the evidence is limited and weak, most of
      these measures did not appear to increase other complications and can be easily
      incorporated into a surgical practice, especially in patients who are at high
      risk for postoperative dysphagia.

PMID- 24662215
TI  - Hyperextension injury in a patient with ochronotic spondyloarthropathy.

PMID- 24662216
TI  - Atlantoaxial instability in acute odontoid fractures is associated with nonunion
      and mortality.
AB  - BACKGROUND CONTEXT: Odontoid fractures are the most common geriatric cervical
      spine fractures. Nonunion rates have been reported to be up to 40% and mortality
      up to 35%, and poor functional outcomes are common. Atlantoaxial instability
      (AAI) is a plausible prognostic factor, but its role has not been previously
      examined. PURPOSE: To determine the effect of severe AAI on the outcomes of
      nonunion and mortality in patients with acute odontoid fractures. STUDY DESIGN:
      Retrospective cohort/single institution. PATIENT SAMPLE: One hundred twenty-four
      consecutive patients with acute odontoid fractures. OUTCOME MEASURES: Rates of
      nonunion and mortality. METHODS: Two independent blinded reviewers measured AAI
      using postinjury computed tomography scans. Patients were classified as having
      "severe" or "minimal" AAI on the basis of greater versus less than or equal to
      50% mean subluxation across each C1-C2 facet joint. Rates of nonunion and
      mortality were compared using independent samples t tests and adjusted for age,
      displacement, and subtype using binary logistic regression. RESULTS: One hundred
      seven patients had minimal AAI and 17 had severe AAI. Mean follow-up was 4.4
      months (standard deviation=4.6). Patients with severe AAI were more likely to
      experience nonunion (29% vs. 10%, respectively; p=.03) and mortality (35% vs.
      14%, respectively; p=.03) regardless of treatment modality. Fracture displacement
      correlated with AAI (r(2)=0.65). When adjusted for patient age, the odds ratio of
      nonunion with severe AAI approached significance at 3.3 (95% confidence interval
      [CI]: 0.9-11.7). Mortality prediction with AAI approached a twofold increased
      risk (odds ratio=2.1; 95% CI: 0.6-6.8). In patients with Type-II fractures, the
      odds of mortality with severe AAI approached a threefold higher risk (odds
      ratio=3.3; 95% CI: 0.9-12.3). CONCLUSIONS: Patients with acute odontoid fractures
      and severe AAI may be more likely to experience nonunion and mortality,
      suggesting the possibility that aggressive management could be warranted. Further
      investigation with a large prospective study including patient-important
      functional outcomes is justified.

PMID- 24662217
TI  - Biomechanics of the lower thoracic spine after decompression and fusion: a
      cadaveric analysis.
AB  - BACKGROUND CONTEXT: Few studies have evaluated the extent of biomechanical
      destabilization of thoracic decompression on the upper and lower thoracic spine.
      The present study evaluates lower thoracic spinal stability after laminectomy,
      unilateral facetectomy, and unilateral costotransversectomy in thoracic spines
      with intact sternocostovertebral articulations. PURPOSE: To assess the
      biomechanical impact of decompression and fixation procedures on lower thoracic
      spine stability. STUDY DESIGN: Biomechanical cadaveric study. METHODS: Sequential
      surgical decompression (laminectomy, unilateral facetectomy, unilateral
      costotransversectomy) and dorsal fixation were performed on the lower thoracic
      spine (T8-T9) of human cadaveric spine specimens with intact rib cages (n=10). An
      industrial robot was used to apply pure moments to simulate flexion-extension
      (FE), lateral bending (LB), and axial rotation (AR) in the intact specimens and
      after decompression and fixation. Global range of motion (ROM) between T1-T12 and
      intrinsic ROM between T7-T11 were measured for each specimen. RESULTS: The
      decompression procedures caused no statistically significant change in either
      global or intrinsic ROM compared with the intact state. Instrumentation, however,
      reduced global motion for AR (45 degrees  vs. 30 degrees , p=.0001), FE (24
      degrees  vs. 19 degrees , p=.02), and LB (47 degrees  vs. 36 degrees , p=.0001)
      and for intrinsic motion for AR (17 degrees  vs. 4 degrees , p=.0001), FE (8
      degrees  vs. 1 degrees , p=.0001), and LB (12 degrees  vs. 1 degrees , p=.0001).
      No significant differences were identified between decompression of the upper
      versus lower thoracic spine, with trends toward significantly greater ROM for AR
      and lower ROM for LB in the lower thoracic spine. CONCLUSIONS: The lower thoracic
      spine was not destabilized by sequential unilateral decompression procedures.
      Addition of dorsal fixation increased segment rigidity at intrinsic levels and
      also reduced overall ROM of the lower thoracic spine to a greater extent than did
      fusing the upper thoracic spine (level of the true ribs). Despite the lack of
      true ribs, the lower thoracic spine was not significantly different compared with
      the upper thoracic spine in FE and LB after decompression, although there were
      trends toward significance for greater AR after decompression. In certain
      patients, instrumentation may not be needed after unilateral decompression of the
      lower thoracic spine; further validation and additional clinical studies are
      warranted.

PMID- 24662218
TI  - Evolution: Cancer drivers everywhere?

PMID- 24662219
TI  - Plant genetics: Plastid genomes - lost in translation?

PMID- 24662220
TI  - Gene expression regulation mediated through reversible m6A RNA methylation.
AB  - Cellular RNAs carry diverse chemical modifications that used to be regarded as
      static and having minor roles in 'fine-tuning' structural and functional
      properties of RNAs. In this Review, we focus on reversible methylation through
      the most prevalent mammalian mRNA internal modification, N(6)-methyladenosine
      (m(6)A). Recent studies have discovered protein 'writers', 'erasers' and
      'readers' of this RNA chemical mark, as well as its dynamic deposition on mRNA
      and other types of nuclear RNA. These findings strongly indicate dynamic
      regulatory roles that are analogous to the well-known reversible epigenetic
      modifications of DNA and histone proteins. This reversible RNA methylation adds a
      new dimension to the developing picture of post-transcriptional regulation of
      gene expression. 

PMID- 24662222
TI  - To clarify features of photoplethysmography in monitoring balanced anesthesia,
      compared with Cerebral State Index.
AB  - BACKGROUND: Although photoplethysmography and cerebral state index (CSI) have
      been used as indices in monitoring vital signs perioperatively, there are only a
      few reports comparing the performance of photoplethysmography with CSI in
      monitoring anaesthesia depth. The aim of the present study was to clarify
      features of photoplethysmography in monitoring balanced general anesthesia
      compared with CSI. MATERIAL AND METHODS: Forty-five patients undergoing elective
      operation under general anaesthesia were enrolled in this study. Anaesthesia was
      induced with target-controlled infusion propofol. The photoplethysmogram, CSI,
      Modified Observer's Assessment of Alertness/Sedation Scale (MOAAS), and mean
      arterial pressure (MAP) were continuously monitored and recorded. Finger
      photoplethysmogram amplitude (PPGA) and pulse beat interval (PBI) were calculated
      off-line. RESULTS: For the period of time from pre-induction to pre-intubation,
      the coefficient of correlation between MOAAS and CSI was higher than those
      between MOAAS and PPGA, PBI, and MAP. CSI showed higher prediction probabilities
      (Pk) to differentiate the levels of MOAAS than did PPGA, PBI, and MAP. PPGA, PBI,
      and MAP values showed significant differences between before and after
      intubation, as well as pre- and post-incision (P<0.05), but no significant
      changes in cerebral state index (P>0.05). CONCLUSIONS: The present study shows
      that photoplethysmography-derived parameters appear to be more suitable in
      monitoring the nociceptive component of balanced general anesthesia, while CSI
      performs well in detecting the sedation or hypnotic component of balanced general
      anesthesia.

PMID- 24662223
TI  - Whole-body vibration combined with extra-load training for enhancing the strength
      and speed of track and field athletes.
AB  - The purpose of this study was to investigate whether whole-body vibration (WBV)
      combined with extra-load training can enhance the strength and speed of trained
      athletes compared with isolated WBV training or loaded training (LT) only. Twenty
      one elite male track and field athletes were randomly assigned to a loaded
      vibration (LV) training group (n = 7), an unloaded vibration (ULV) training group
      (n = 7), and a LT group (n = 7). During 4 weeks of training, the LV group
      received the vibration stimulus (30 Hz and 4 mm) accompanied by a load comprising
      75% of the maximum voluntary contraction (MVC), the ULV group received the same
      vibration stimulus without any load, and the LT group received only a load of 75%
      MVC without any vibration stimulus. The knee extensor isometric strength, and the
      concentric and eccentric strength were measured using an isokinetic dynamometer
      at 300 degrees .s at a 30-m sprint speed before and after the training period. A
      2-way mixed analysis of variance (time * group) was used to analyze the
      differences. Significant time * group interactions were observed for all the
      dependent variables (p <= 0.05). Regarding the post hoc analysis results, the LV
      group exhibited significant improvements for all the dependent variables after
      training (p <= 0.05), whereas the ULV group exhibited significantly reduced
      sprint speeds (p <= 0.05). The LV group demonstrated significantly superior
      eccentric strength compared with the ULV and LT groups after training (p <=
      0.05), and the LV group also produced significantly superior sprint speeds
      compared with the ULV group after training (p <= 0.05). Vibration combined with
      extra-load training for 4 weeks significantly increased the muscle strength and
      speed of the elite male track and field athletes.

PMID- 24662224
TI  - Effects of nonlinear resistance and aerobic interval training on cytokines and
      insulin resistance in sedentary men who are obese.
AB  - Regular exercise training has been shown to reduce systemic inflammation, but
      there is limited research directly comparing different types of training. The
      purpose of this study was to compare the effects of nonlinear resistance training
      (NRT) and aerobic interval training (AIT) on serum interleukin-10 (IL-10), IL-20,
      and tumor necrosis factor-alpha (TNF-alpha) levels, insulin resistance index
      (homeostasis model assessment of insulin resistance), and aerobic capacity in
      middle-aged men who are obese. Sedentary volunteers were assigned to NRT (n =
      12), AIT (n = 12), and (CON, n = 10) control groups. The experimental groups
      performed 3 weekly sessions for 12 weeks, whereas the CON grouped maintained a
      sedentary lifestyle. Nonlinear resistance training consisted of 40-65 minutes of
      weight training at different intensities with flexible periodization. Aerobic
      interval training consisted of running on a treadmill (4 sets of 4 minutes at 80
      90% of maximal heart rate, with 3-minute recovery intervals). Serum IL-10, IL-20,
      and TNF-alpha levels did not change significantly in response to training (all p
      > 0.05), but IL-10:TNF-alpha ratio increased significantly with AIT compared with
      CON (2.95 +/- 0.84 vs. 2.52 +/- 0.65; p = 0.02). After the training period,
      maximal oxygen uptake increased significantly in AIT and NRT compared with CON
      (both p < 0.001; 46.7 +/- 5.9, 45.1 +/- 3.2, and 41.1 +/- 4.7 ml.kg.min,
      respectively) and in AIT than in NRT (p = 0.001). The 2 exercise programs were
      equally effective at reducing insulin resistance (homeostasis model assessment
      for insulin resistance) (both p <= 0.05; AIT: 0.84 +/- 0.34, NRT: 0.84 +/- 0.27,
      and CON: 1.62 +/- 0.56) and fasting insulin levels (both p <= 0.05; AIT: 3.61 +/-
      1.48, NRT: 3.66 +/- 0.92, and CON: 6.20 +/- 2.64 MUU.ml), but the AIT seems to
      have better anti-inflammatory effects (as indicated by the IL-10:TNF-alpha ratio)
      compared with NRT.

PMID- 24662225
TI  - Seasonal changes in anthropometric and physical characteristics within English
      academy rugby league players.
AB  - Professional rugby league clubs implement training programmes for the development
      of anthropometric and physical characteristics within an academy programme.
      However, research that examines seasonal changes in these characteristics is
      limited. The purpose of the study was to evaluate the seasonal changes in
      anthropometric and physical characteristics of academy rugby league players by
      age category (i.e., under 14, 16, 18, 20). Data were collected on 75 players pre-
      and postseason over a 6-year period (resulting in a total of 195 assessments).
      Anthropometric (body mass, sum of 4 skinfolds) and physical (10- and 20-m sprint,
      vertical jump, Yo-Yo intermittent recovery test and 1 repetition maximum squat,
      bench press, and prone row) measures were collected. The under 14s and 16s showed
      greater seasonal improvements in body mass (e.g., under 14s = 7.4 +/- 4.3% vs.
      under 20s = 1.2 +/- 3.3%) and vertical jump performance than under 18s and under
      20s. In contrast, under 18s and under 20s players showed greater seasonal
      improvements in Yo-Yo performance and 10-m sprint (e.g., under 14s = 1.3 +/- 3.9%
      vs. under 20s = -1.9 +/- 1.2%) in comparison to under 14s and under 16s. Seasonal
      strength improvements were greater for the under 18s compared with under 20s.
      This study provides comparative data for seasonal changes in anthropometric and
      physical characteristics within rugby league players aged 13-20 years. Coaches
      should be aware that seasonal improvements in speed may not exist within younger
      age categories, until changes in body mass stabilize and consider monitoring
      changes in other characteristics (e.g., momentum). Large interplayer variability
      suggests that player development should be considered on an individual and
      longitudinal basis.

PMID- 24662221
TI  - Genomic insights into tuberculosis.
AB  - Prevalent since pre-history, human tuberculosis - caused by the pathogen
      Mycobacterium tuberculosis - remains a major source of death worldwide. Moreover,
      increasing drug resistance poses the threat of disease resurgence. However, the
      expanding application of genomic techniques is providing new avenues for
      combating this old foe. Whole-genome sequencing, comparative genomics and systems
      biology are generating new insights into the origins and ongoing evolution of M.
      tuberculosis, as well as the molecular basis for its pathogenicity. These have
      important implications for our perspective of the disease, development of new
      drugs and vaccines, and treatment of patients using existing therapeutics. 

PMID- 24662226
TI  - Comparison of running characteristics and heart rate response of international
      and national female rugby sevens players during competitive matches.
AB  - This study compared the activity profile of national and international female
      rugby sevens players during competitive matches. Twenty rugby sevens female
      players were recruited, 10 were members of the Spanish National Team (26.27 +/-
      4.05 years, 65.39 +/- 5.01 kg, 166.72 +/- 6.70 cm) and 10 were amateur athletes
      from a Spanish rugby championship (32.12 +/- 6.40 years, 66.48 +/- 5.38 kg of
      body mass, 167.37 +/- 3.02 cm). Data collection was conducted over 4 matches in
      each of the 2 tournaments, national and international. Distance, velocity, and
      heart rate (HR) were recorded using global positioning system devices for all
      participants throughout each match. There were significant differences (p < 0.01)
      in total distance (1642 +/- 171 vs. 1363 +/- 222 m), average speed (6.0 +/- 0.3
      vs. 5.2 +/- 0.6 km.h-1), number of sprints (6.1 +/- 3.1 vs. 1.9 +/- 1.4 sprints),
      and distance covered in sprinting (118.8 +/- 61.4 vs. 47.0 +/- 38.8 m).
      Significant differences were found at >95% maximum HR (HRmax), both for the first
      (p < 0.01) and second half (p <= 0.05). The work-rest ratio was significantly
      different (p < 0.01) between international (1:0.3) and national players (1:0.4).
      Significant differences were found in accelerations above 2 m.s-2 in the first
      and second half between the 2 groups. These findings suggest that distance
      covered in a match and speed are considerably different between international and
      national rugby sevens players, and this is reflected as higher intensity of play
      with consequently higher HR. Coaches may use this information to design specific
      running drills for this athlete population to match the requirements of national
      or international game play.

PMID- 24662227
TI  - Comparing three devices for jump height measurement in a heterogeneous group of
      subjects.
AB  - The purpose of this study was to compare the accuracy of 3 devices for measuring
      jump heights of subjects with a range of abilities. The methods used were an
      accelerometer-based technique (KineJump), a contact mat (Newtest Powertimer 300
      series), and the Vertec measurement device. The reference method used was a video
      analysis technique. Data were collected simultaneously with all 4 methods. Of
      particular interest was to evaluate the accuracy of the accelerometer device
      (KineJump) because it has not been systematically compared with other methods in
      the previous literature. Participants (N = 101) varied from well-trained athletes
      to sedentary individuals and their ages ranging from 18 to 70 years old. From the
      statistical analysis, it can be concluded that KineJump has accuracy that is at
      least as good as the accuracy of the Vertec and contact mat, although the overall
      accuracy of all the methods was disappointing at typically +/- 5 cm. The 2
      methods that rely on a time-of-flight calculation of the jump height (contact mat
      and accelerometer) showed systematically lower values than the other 2 methods.
      None of the physical parameters showed significant correlation with the
      measurement error made by the methods, with the exception of a slight positive
      correlation of height, leg length, and foot length to the error of the Vertec
      method. Linear regression on the Bland-Altman plots did not reveal a significant
      correlation between the jump height and the error of a method, except for the
      Vertec. The 3 jump height measurement devices can be used to evaluate performance
      in a diverse group of people, but considerable deviation from actual jump height
      is apparent, depending on the method of calculation.

PMID- 24662228
TI  - Electromyographic and kinetic comparison of the back squat and overhead squat.
AB  - The purpose of this study was to compare muscle activity and kinetics during the
      back squat and overhead squat performed at 3 relative intensities (60, 75, and
      90% 3 repetition maximum). Fourteen subjects (age, 26 +/- 7 years; height, 182.5
      +/- 13.5 cm; body mass, 90.5 +/- 17.5 kg) performed each exercise using a within
      subjects crossover design. In addition, a selection of trunk isolation exercises
      were included to provide additional comparisons. Squats were performed on a force
      platform with electromyographic activity of the anterior deltoid, rectus
      abdominis (RA), external oblique (EO), erector spinae (ES), gluteus maximus,
      vastus lateralis, biceps femoris, and lateral gastrocnemius recorded throughout.
      The overhead squat demonstrated significantly greater (p <= 0.05) activity in the
      anterior trunk muscles (RA and EO) during the eccentric phase. However, the
      magnitudes of the differences were relatively small (approximately 2-7%). In
      contrast, the back squat displayed significantly greater (p <= 0.05) activity in
      the posterior aspect of the trunk ES and all lower-body muscles during the
      concentric phase. Kinetic comparisons revealed that significantly greater peak
      force (p <= 0.05) was developed during the back squat. Electromyographic
      comparisons between the trunk isolation exercises and squat variations
      demonstrated substantially greater anterior trunk activity during the isolation
      exercises, whereas the highest activity in the posterior aspect of the trunk was
      obtained during the squats (p <= 0.05). The results of the study do not support
      the hypothesis that the overhead squat provides a substantially greater stimulus
      for developing the trunk musculature compared with the back squat.

PMID- 24662229
TI  - Establishing the criterion validity and reliability of common methods for
      quantifying training load.
AB  - The purpose of this investigation was to compare the criterion validity and test
      retest reliability of common methods for quantifying training load. Ten (5 men
      and 5 women) recreational athletes (mean +/- SD, VO2max: 37.0 +/- 4.3 ml.kg-1.min
      1; age: 23.8 +/- 8.4 years) completed 18 randomly assigned steady state (SS) and
      interval (INT) training sessions during a 6-week period. Steady-state sessions
      were 18 minutes in duration and were performed at 35, 50, and 65% of maximum work
      capacity (Wmax). Interval sessions were performed at 50, 60, and 70% of Wmax with
      a work to rest ratio of 1:1 and matched for total work with the 50% SS session.
      Oxygen consumption (VO2) and heart rate (HR) were measured throughout all
      sessions, whereas blood lactate concentration and rating of perceived exertion
      (RPE) measures were taken every 6 minutes during sessions. Session-RPE (sRPE) was
      collected after each exercise bout. All individual correlations between VO2 and
      external work (r = 0.88-0.97), HR (r = 0.65-0.90), and RPE-based methods (r =
      0.55-0.89) were statistically significant. External work correlated best with the
      total V[Combining Dot Above]O2 and was significantly different from RPE-based
      methods. A poor level of test-retest reliability was shown for Banister's TRIMP
      (15.6% coefficient of variation [CV]), Lucia's TRIMP (10.7% CV), and sRPE (28.1%
      CV). Good reliability was shown for HR (3.9% CV) and a moderate level for RPE 6
      20 (8.5% CV) as a measure of exercise intensity. These results suggest external
      work to be the most valid and reliable method for quantifying training load. Poor
      levels of reliability were reported for each of the HR-based TRIMP methods and
      RPE-based methods.

PMID- 24662230
TI  - Effects of additional repeated sprint training during preseason on performance,
      heart rate variability, and stress symptoms in futsal players: a randomized
      controlled trial.
AB  - The aim of this study was to investigate whether supplementing regular preseason
      futsal training with weekly sessions of repeated sprints (RS) training would have
      positive effects on repeated sprint ability (RSA) and field test performance.
      Thirteen players from a professional futsal team (22.6 +/- 6.7 years, 72.8 +/-
      8.7 kg, 173.2 +/- 6.2 cm) were divided randomly into 2 groups (AddT: n = 6 and
      normal training group: n = 7). Both groups performed a RSA test, Yo-Yo
      intermittent recovery test level 1 (YoYo IR1), squat (SJ) and countermovement
      jumps (CMJ), body composition, and heart rate variability (HRV) measures at rest
      before and after 4 weeks of preseason training. Athletes weekly stress symptoms
      were recorded by psychometric responses using the Daily Analysis of Life Demands
      for Athletes questionnaire and subjective ratings of well-being scale,
      respectively. The daily training load (arbitrary units) was assessed using the
      session of rating perceived exertion method. After the preseason training, there
      were no significant changes for body composition, SJ, CMJ, and RSAbest. The YoYo
      IR1, RSAmean, RSAworst, and RSAdecreament were significantly improved for both
      groups (p <= 0.05). The HRV parameters improved significantly within both groups
      (p <= 0.05) except for high frequency (HF, absolute and normalized units,
      [n.u.]), low frequency (LF) (n.u.), and the LF/HF ratio. A moderate effect size
      for the AddT group was observed for resting heart rate and several HRV measures.
      Training load and psychometric responses were similar between both groups.
      Additional RS training resulted in slightly greater positive changes for vagal
      related HRV with similar improvements in performance and training stress during
      the preseason training in futsal players.

PMID- 24662231
TI  - Comparison Between the Effects of Combining Elastic and Free-Weight Resistance
      and Free-Weight Resistance on Force and Power Production.
AB  - Paditsaeree, K, Intiraporn, C, and Lawsirirat, C. Comparison between the effects
      of combining elastic and free-weight resistance and free-weight resistance on
      force and power production. J Strength Cond Res 30(10): 2713-2722, 2016-Elastic
      tubing attached to a barbell has been reported to enhance strength and power to a
      greater extent as compared with conventional barbells. The aim of this study was
      to investigate the effect of the additional elastic tubing to a barbell during a
      clean pull on peak power (PP), peak velocity (PV), and peak force (PF). Six
      competitive female weightlifters (mean age, 16.7 +/- 2.1 years) performed 3 sets
      of 3 repetitions of the clean pull at 90% of 1 repetition maximum (1RM). Testing
      was conducted on 3 separate days: day 1 without elastic tubing (no tubing [NT])
      and the other 2 days with 2 elastic tubing loading conditions (T10 and T20), in
      random order. No tubing represents a condition where all resistance was acquired
      from the barbell (90% of 1RM). T10 and T20 represent conditions of combining
      elastic tubing at 10 and 20% of the subjects' 90% 1RM with a barbell (90% of
      1RM). One-way repeated-measures analysis of variance was used to assess loading
      conditions on PP, PV, and PF. The results showed that there was a significant
      increase in all variables-PP, PF, and PV-between T10 and NT and between T20 and
      NT (p <= 0.05). The results revealed that adding a 10% increment to 90% of 1RM
      seems to be the optimal training condition for increasing power, force, and
      velocity during the clean pull. 

PMID- 24662232
TI  - Biomechanical factors associated with time to complete a change of direction
      cutting maneuver.
AB  - Cutting ability is an important aspect of many team sports, however, the
      biomechanical determinants of cutting performance are not well understood. This
      study aimed to address this issue by identifying the kinetic and kinematic
      factors correlated with the time to complete a cutting maneuver. In addition, an
      analysis of the test-retest reliability of all biomechanical measures was
      performed. Fifteen (n = 15) elite multidirectional sports players (Gaelic
      hurling) were recruited, and a 3-dimensional motion capture analysis of a 75
      degrees  cut was undertaken. The factors associated with cutting time were
      determined using bivariate Pearson's correlations. Intraclass correlation
      coefficients (ICCs) were used to examine the test-retest reliability of
      biomechanical measures. Five biomechanical factors were associated with cutting
      time (2.28 +/- 0.11 seconds): peak ankle power (r = 0.77), peak ankle plantar
      flexor moment (r = 0.65), range of pelvis lateral tilt (r = -0.54), maximum
      thorax lateral rotation angle (r = 0.51), and total ground contact time (r = 
      0.48). Intraclass correlation coefficient scores for these 5 factors, and indeed
      for the majority of the other biomechanical measures, ranged from good to
      excellent (ICC >0.60). Explosive force production about the ankle, pelvic control
      during single-limb support, and torso rotation toward the desired direction of
      travel were all key factors associated with cutting time. These findings should
      assist in the development of more effective training programs aimed at improving
      similar cutting performances. In addition, test-retest reliability scores were
      generally strong, therefore, motion capture techniques seem well placed to
      further investigate the determinants of cutting ability.

PMID- 24662233
TI  - The relationships between internal and external training load models during
      basketball training.
AB  - The present investigation described and compared the internal and external
      training loads during basketball training. Eight semiprofessional male basketball
      players (mean +/- SD, age: 26.3 +/- 6.7 years; stature: 188.1 +/- 6.2 cm; body
      mass: 92.0 +/- 13.8 kg) were monitored across a 7-week period during the
      preparatory phase of the annual training plan. A total of 44 total sessions were
      monitored. Player session ratings of perceived exertion (sRPE), heart rate, and
      accelerometer data were collected across each training session. Internal training
      load was determined using the sRPE, training impulse (TRIMP), and summated-heart
      rate-zones (SHRZ) training load models. External training load was calculated
      using an established accelerometer algorithm. Pearson product-moment correlations
      with 95% confidence intervals (CIs) were used to determine the relationships
      between internal and external training load models. Significant moderate
      relationships were observed between external training load and the sRPE (r42 =
      0.49, 95% CI = 0.23-0.69, p < 0.001) and TRIMP models (r42 = 0.38, 95% CI = 0.09
      0.61, p = 0.011). A significant large correlation was evident between external
      training load and the SHRZ model (r42 = 0.61, 95% CI = 0.38-0.77, p < 0.001).
      Although significant relationships were found between internal and external
      training load models, the magnitude of the correlations and low commonality
      suggest that internal training load models measure different constructs of the
      training process than the accelerometer training load model in basketball
      settings. Basketball coaching and conditioning professionals should not assume a
      linear dose-response between accelerometer and internal training load models
      during training and are recommended to combine internal and external approaches
      when monitoring training load in players.

PMID- 24662234
TI  - The efficacy of incorporating partial squats in maximal strength training.
AB  - The purpose of our study was to examine the effects of 2 different training
      methods on dynamic and isometric measures of maximal strength. Seventeen
      recreationally trained men (1 repetition maximum [1RM] squat: 146.9 +/- 22.4 kg)
      were assigned to 2 groups: full range of motion (ROM) squat (F) and full ROM with
      partial ROM squat (FP) for the 7-week training intervention. Repeated measures
      analysis of variance revealed that there was a statistically significant group-by
      time interaction for impulse scaled at 50, 90, and 250 milliseconds at 90 degrees
      of knee flexion and rate of force development at 200 milliseconds with 120
      degrees  of knee flexion (p <= 0.05). There was also a statistically significant
      time effect (p <= 0.05) for the 1RM squat, 1RM partial squat, isometric squat
      peak force allometrically scaled (IPFa) 90 degrees , IPFa 120 degrees , and
      impulse allometrically scaled at 50, 90, 200, and 250 milliseconds at 90 degrees 
      and 120 degrees  of knee flexion. Additionally, the FP group achieved
      statistically larger relative training intensities (%1RM) during the final 3
      weeks of training (p <= 0.05). There was a trend for FP to improve over F in 1RM
      squat (+3.1%, d = 0.53 vs. 0.32), 1RM partial squat (+4.7%, d = 0.95 vs. 0.69),
      IPFa 120 degrees  (+5.7%, d = 0.52 vs. 0.12), and impulse scaled at 50, 90, 200,
      and 250 milliseconds at 90 degrees  (+6.3 to 13.2%, d = 0.50-1.01 vs. 0.30-0.57)
      and 120 degrees  (+3.4 to 16.8%, d = 0.45-1.11 vs. 0.08-0.37). These larger
      effect sizes in the FP group can likely be explained their ability to train at
      larger relative training intensities during the final 3 weeks of training
      resulting in superior training adaptations. Our findings suggest that partial ROM
      squats in conjunction with full ROM squats may be an effective training method
      for improving maximal strength and early force-time curve characteristics in men
      with previous strength training experience. Practically, partial squats may be
      beneficial for strength and power athletes during a strength-speed mesocycle
      while peaking for competition.

PMID- 24662235
TI  - Influence of linear and undulating strength periodization on physical fitness,
      physiological, and performance responses to simulated judo matches.
AB  - To determine the most effective strength periodization model is important to
      improve judo athletes' performance. Thus, the aim of this study was to compare
      the effects of linear and daily undulating periodized resistance training on
      anthropometrical, strength, and judo-specific performance. For this, 13 adult
      male judo athletes (LP = 6 and DUP = 7) completed a 8-week training program
      concomitantly to a typical judo training program. Athletes were submitted to a
      physical fitness test battery, before and after 8 weeks of training, consisting
      of: (a) maximal strength evaluation: bench press, squat, and row exercises 1
      repetition maximum (1RM) tests, and handgrip maximal isometric strength; (b)
      power evaluation: standing long jump test; (c) strength endurance evaluation:
      dynamic and isometric chin-up tests gripping the judogi; (d) anthropometry
      measurements: body mass, height, skinfold thickness and circumferences; (e) judo
      specific fitness: performance during the Special Judo Fitness Test (SJFT); (f)
      match simulation: three 5-minute judo match simulations separated by 15-minute
      passive recovery. Eight weeks of linear and undulating strength training
      protocols induced similar significant (P <= 0.05) decreases in skinfold
      thicknesses (-6.5%) and increases in flexed arm (2.0%) and forearm (1.8%)
      circumferences, maximal isometric handgrip strength (4.6% and 6.1% for right and
      left hands, respectively), isometric strength endurance chin-up performance
      gripping the judogi (18.9%), maximal dynamic strength for row (11.5%), bench
      press (11.6%) and squat exercises (7.1%), total weight lifted at 70% 1RM for
      bench press (15.1%) and squat (9.6%) exercises, number of throws during sets B
      (3.1%) and C (9.5%) of the SJFT (resulting in increased total number of throws,
      5.5%), and decreased index in this test, -4.2%). However, no changes were
      observed in the physiological, rating of perceived exertion, or technical actions
      during 3 match simulations. Thus, it seems that the short-term adaptations were
      not transferable to the match condition.

PMID- 24662236
TI  - High completeness of the brest stroke registry evidenced by analysis of sources
      and capture-recapture method.
AB  - BACKGROUND: Population-based stroke registries are necessary to evaluate the
      precise burden of stroke. The methodology used in the Brest Stroke Registry and
      an estimation of its completeness are described. METHODS: 'Hot pursuit' as well
      as 'cold pursuit' were used, and five sources of identification were included:
      emergency wards, brain imaging, practitioners, death certificates and hospital
      based electronic research. Ascertainment for each case was certified by a
      neurologist. Inclusion criteria were: (1) age >15 years; (2) a stroke defined by
      WHO criteria or all neurological deficits lasting at least 1 h. Completeness was
      estimated using capture-recapture method. RESULTS: For 2008, 2009 and 2010, 851,
      898, 823 patients were collected, respectively. The number of sources of
      identification per patient was as follows: one source: 30.8, 24.1 and 18.7%; two
      sources: 54.5, 42.9 and 31.0%; three sources: 13.4, 30.1 and 46%; four sources:
      1.3, 3.0 and 3.8%. Capture-recapture analysis showed data completeness over 90%.
      Standardized cumulative first-ever stroke incidence using a world standard
      population was 87 in 2008, 87 in 2009 and 84 in 2010. CONCLUSIONS: Case
      ascertainment by a neurologist, numerous sources, as well as 'hot' and 'cold'
      pursuit can provide a reliably large data set suitable for further
      epidemiological studies.

PMID- 24662237
TI  - The 'surprise' question in advanced cancer patients: A prospective study among
      general practitioners.
AB  - BACKGROUND: Using the 'surprise' question 'Would you be surprised if this patient
      died in the next year?' may improve physicians' prognostic accuracy and identify
      people appropriate for palliative care. AIM: Determine the prognostic accuracy of
      general practitioners asking the 'surprise' question about their patients with
      advanced (stage IV) cancer. DESIGN: Prospective cohort study.
      SETTING/PARTICIPANTS: Between December 2011 and February 2012, 42 of 50 randomly
      selected general practitioners (Bologna area, Italy) prospectively classified 231
      patients diagnosed with advanced cancer according to the 'surprise' question and
      supplied the status of each patient 1 year later. RESULTS: Of the 231 patients,
      general practitioners responded 'No' to the 'surprise' question for 126 (54.5%)
      and 'Yes' for 105 (45.5%). After 12 months, 104 (45.0%) patients had died; 87
      (83.7%) were in the 'No' group. The sensitivity of the 'surprise' question was
      69.3%; the specificity was 83.6%. Positive predictive value was 83.8%; negative
      predictive value was 69.0%. The answer to the 'surprise' question was
      significantly correlated with survival at 1 year. Patients in the 'No' group had
      an odds ratio of 11.55 (95% confidence interval: 5.83-23.28) and a hazard ratio
      of 6.99 (95% confidence interval: 3.75-13.03) of being dead in the next year
      compared to patients in the 'Yes' group (p = 0.000 for both odds ratio and hazard
      ratio). CONCLUSION: When general practitioners used the 'surprise' question for
      their patients with advanced cancer, the accuracy of survival prognosis was very
      high. This has clinical potential as a method to identify patients who might
      benefit from palliative care.

PMID- 24662238
TI  - Is There a Relationship Between Tic Frequency and Physiological Arousal?
      Examination in a Sample of Children With Co-Occurring Tic and Anxiety Disorders.
AB  - Stress is the contextual variable most commonly implicated in tic exacerbations.
      However, research examining associations between tics, stressors, and the
      biological stress response has yielded mixed results. This study examined whether
      tics occur at a greater frequency during discrete periods of heightened
      physiological arousal. Children with co-occurring tic and anxiety disorders (n =
      8) completed two stress-induction tasks (discussion of family conflict, public
      speech). Observational (tic frequencies) and physiological (heart rate [HR]) data
      were synchronized using The Observer XT, and tic frequencies were compared across
      periods of high and low HR. Tic frequencies across the entire experiment did not
      increase during periods of higher HR. During the speech task, tic frequencies
      were significantly lower during periods of higher HR. Results suggest that tic
      exacerbations may not be associated with heightened physiological arousal and
      highlight the need for further tic research using integrated measurement of
      behavioral and biological processes. 

PMID- 24662239
TI  - Contralateral axillary metastases from breast cancer. Personal experience and
      review of literature.
AB  - The contralateral axillary lymph node metastasis (CAM) from breast cancer are
      very rare, and pose a number of classification problems and therefore also on the
      surgery attitude to be adopted and the subsequent surgical oncological approach,
      making a distinction between synchronous and metachronous cases. You must always
      wait for a reasonable period of time to exclude the presence of an occult cancer
      in the contralateral breast. You make assumptions about the lymphatic pathways
      that determine this metastasis underlining that in the literature (rare) cases
      are reported in which the lymphoscintigraphic sentinel lymph node search has
      shown an uptake of contralateral axillary lymph nodes. KEY WORDS: Breast cancer,
      Controlateral axillary lymph node metastasis, Lymph node metastasis.

PMID- 24662240
TI  - Downregulation of angiotensin-converting enzyme 2 by the neuraminidase protein of
      influenza A (H1N1) virus.
AB  - Influenza A (H1N1) virus, a high-risk infectious pathogen, can cause severe acute
      lung injury leading to significant morbidity and mortality. Angiotensin
      converting enzyme 2 (ACE2), a negative regulator of the renin-angiotensin system
      (RAS), plays a protective role in pathogenesis of acute lung injury. Here, we
      showed that ACE2 protein levels were significantly downregulated after infection
      with H1N1 viruses but was dispensable for viral replication. ACE2 protein
      downregulation was most likely related to ACE2 protein degradation by proteasome
      pathway rather than ACE2 shedding. Finally, we found that ACE2 cleavage could be
      regulated by influenza neuraminidase (NA), which was fundamentally different from
      the classically sheddase-induced proteolytic cleavage of ACE2. 

PMID- 24662241
TI  - Providing clean drinking water in schools encourages attendance, study finds.

PMID- 24662242
TI  - Immune tolerance of epithelium-denuded-cryopreserved tracheal allograft.
AB  - OBJECTIVES: Animal and clinical studies have demonstrated the feasibility of
      tracheal allograft transplantation after a revascularization period in
      heterotopy, thus requiring immunosuppressive therapy. Given the key role of the
      respiratory epithelium in the immune rejection, we investigated the consequence
      of both epithelium denudation and cryopreservation in immune tolerance of
      tracheal allograft in a novel rabbit model. METHODS: Five adult female New
      Zealand rabbits served as donors of tracheas that were denuded of their
      epithelium and then cryopreserved, and 13 males were used as recipients.
      Following graft wrap using a lateral thoracic fascial flap, allograft segments 20
      mm in length with (n = 9) or without (n = 4) insertion of an endoluminal tube
      were implanted under the skin of the chest wall. The animals did not receive any
      immunosuppressive drugs. Sacrifices were scheduled up to 91 days. Macroscopic and
      microscopic examinations and detection of apoptotic cells by immunohistochemical
      staining (Apostain) were used to study the morphology, stiffness, viability and
      immune rejection of allografts. RESULTS: There were no postoperative
      complications. Grafted composite allografts displayed satisfactory tubular
      morphology provided that an endoluminal tube was inserted. All rabbits were found
      to have an effective revascularization of their allograft and a mild non-specific
      inflammatory infiltrate with no significant lymphocyte infiltration. Cartilage
      rings showed early central calcification deposit, which increased over time,
      ensuring graft stiffness. Apoptosis events observed into the allograft cells were
      suggestive of minimal chronic rejection. CONCLUSIONS: Our results demonstrated
      that the epithelium-denuded-cryopreserved tracheal allograft implanted in
      heterotopy displayed satisfactory morphology, stiffness and immune tolerance
      despite the absence of immunosuppressive drugs. This allograft with a fascial
      flap transferable to the neck should be investigated in the setting of tracheal
      replacement in rabbits. Similar studies need to be conducted in bigger mammals
      before considering clinical applications.

PMID- 24662244
TI  - Older age at the time of the Norwood procedure is a risk factor for early
      postoperative mortality?.
AB  - OBJECTIVES: The Norwood procedure is commonly used as first-step palliation in
      children with hypoplastic left heart syndrome or related congenital
      malformations. In most cases, the operation is carried out during the first week
      of life. Excessive pulmonary blood flow in univentricular physiology can soon
      lead to compromised cardiac function and pulmonary hypertension and could have an
      influence on postoperative outcomes. METHODS: Between 1997 and 2011, 257 Norwood
      procedures were performed at the Kinderherz-Zentrum Linz. Twenty-seven patients
      were older than 20 days at the time of the Norwood operation without previous
      pulmonary artery banding. A retrospective analysis of the two age groups was
      carried out concerning early mortality, interstage mortality and major events
      until the bidirectional Glenn operation. RESULTS: Patients older than 20 days had
      a significantly higher mortality rate before the bidirectional Glenn operation
      than younger patients (44.4 vs 20.3%; P = 0.002). They also showed a
      significantly higher need for postoperative inhalative nitric oxide therapy (40.7
      vs 14.5%, P = 0.002). Summarized risk for either successful postoperative
      cardiopulmonary resuscitation (CPR), extracorporeal membrane oxygenation therapy
      or mortality before the bidirectional Glenn operation was 59.3% in the older age
      group vs 23.8% in the younger age group (P < 0.001). CONCLUSIONS: Age older than
      20 days seems to be an independent risk factor for early postoperative mortality
      and fatal events after the Norwood procedure. Long-persisting excessive pulmonary
      blood flow and preoperative cardiac decompensation can be the reason for
      postoperative lethal pulmonary hypertensive crisis and compromised ventricular
      function.

PMID- 24662243
TI  - Three-year outcomes after percutaneous coronary intervention and coronary artery
      bypass grafting in patients with heart failure: from the CREDO-Kyoto percutaneous
      coronary intervention/coronary artery bypass graft registry cohort-2?.
AB  - OBJECTIVES: Ischaemic heart disease is a major risk factor for heart failure.
      However, long-term benefit of percutaneous coronary intervention (PCI) or
      coronary artery bypass grafting (CABG) in those patients has not been well
      elucidated. METHODS: Of the 15 939 patients undergoing first myocardial
      revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2, we
      identified 1064 patients with multivessel and/or left main disease with a history
      of heart failure (ACC/AHA Stage C or D). RESULTS: There were 672 patients
      undergoing PCI and 392 CABG. Preprocedural left ventricular ejection fraction was
      not different between PCI and CABG (46.6 +/- 15.1 vs 46.6 +/- 14.6%, P = 0.89),
      but the CABG group included more patients with triple-vessel and left main
      disease (P < 0.01 each). Three-year outcomes revealed that the risk of hospital
      readmission for heart failure was higher after PCI than after CABG (hazard ratio
      [95% confidence interval]; 1.90 [1.18-3.05], P = 0.01). More importantly,
      adjusted mortality after PCI was significantly higher than after CABG (1.79 [1.13
      2.82], P = 0.01). The risk of cardiac death after PCI was also higher than after
      CABG (1.98 [1.10-3.55], P = 0.02). Stratified analysis using the SYNTAX score
      demonstrated that risk of death was not different between PCI and CABG in
      patients with low (<23) and intermediate (23-32) SYNTAX scores (2.10 [0.57-7.68],
      P = 0.26 and 1.43 [0.63-3.21], P = 0.39, respectively), whereas those with a high
      (>= 33) SYNTAX score, the risk of death was far higher after PCI than after CABG
      (4.83 [1.46-16.0], P = 0.01). CONCLUSIONS: In patients with heart failure with
      advanced coronary artery disease, CABG was a better option than PCI because CABG
      was associated with better survival benefit, particularly in more complex
      coronary lesions stratified by the SYNTAX score.

PMID- 24662245
TI  - Mutations in epigenetic regulators including SETD2 are gained during relapse in
      paediatric acute lymphoblastic leukaemia.
AB  - Relapsed paediatric acute lymphoblastic leukaemia (ALL) has high rates of
      treatment failure. Epigenetic regulators have been proposed as modulators of
      chemoresistance, here, we sequence genes encoding epigenetic regulators in
      matched diagnosis-remission-relapse ALL samples. We find significant enrichment
      of mutations in epigenetic regulators at relapse with recurrent somatic mutations
      in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signalling factors are not
      enriched. Somatic alterations in SETD2, including frameshift and nonsense
      mutations, are present at 12% in a large de novo ALL patient cohort. We conclude
      that the enrichment of mutations in epigenetic regulators at relapse is
      consistent with a role in mediating therapy resistance. 

PMID- 24662246
TI  - Brain tumors of infancy--an institutional experience and review of the
      literature.
AB  - INTRODUCTION: Brain tumors in infants are rare and form a distinct subgroup of
      pediatric brain tumors. These tumors differ from tumors in older children with
      respect to histology and management and tend to have a poorer outcome. METHODS:
      We analyzed 31 consecutive cases of brain tumors in infancy managed in our
      institute in the last 15 years and reviewed the published literature since 1990.
      RESULTS: Only 2 of these patients had congenital tumors. Choroid plexus tumors
      were the most common histological subtype, followed by medulloblastoma; 62% of
      patients underwent a gross total or near-total excision of the tumor with 1
      perioperative mortality; 68% of patients had a good outcome. CONCLUSION: Choroid
      plexus tumors were the most common histological type. Safe resection should be
      the goal of surgery. Surgeries for tumors in this age group were associated with
      lower rates of total excision and higher morbidity. Low-grade lesions as expected
      are associated with longer survival; however, long-term outcomes are far from
      satisfactory.

PMID- 24662247
TI  - In vitro inhibitory effect of miltefosine against strains of Histoplasma
      capsulatum var. capsulatum and Sporothrix spp.
AB  - Miltefosine (MIL), originally developed for use in cancer chemotherapy, has been
      shown to have important antifungal activity against several pathogenic fungi. Our
      aim in this study was to determine the in vitro activity of MIL against the
      dimorphic fungi Histoplasma capsulatum and Sporothrix spp. This was done using
      the broth microdilution method. MIL had an in vitro inhibitory effect against all
      strains of H. capsulatum var. capsulatum and Sporothrix spp. analyzed. The
      minimal inhibitory concentrations (MIC) varied from 0.25 MUg/ml to 2 MUg/ml for
      H. capsulatum var. capsulatum in the filamentous phase and from 0.125 MUg/ml to 1
      MUg/ml in the yeast phase. The MIC interval for Sporothrix spp. in the
      filamentous phase was 0.25-2 MUg/ml. The minimal fungicidal concentrations (MFCs)
      were <=4 MUg/ml for isolates of both analyzed species. This study demonstrates
      that MIL has an antifungal effect in vitro against two potentially pathogenic
      fungi and that more studies should be performed in order to evaluate its
      applicability in vivo. 

PMID- 24662248
TI  - Potential role of Candida albicans germ tube antibody in the diagnosis of deep
      seated candidemia.
AB  - Patients with candidemia may have transient or catheter-related infections
      without involvement of deep tissues or deep-seated candidiasis. Clinical
      differentiation of these entities may not be evident with conventional
      microbiological and imaging methods. Our aim was to determine if the detection of
      Candida albicans germ tube-specific antibody (CAGTA) in patients with candidemia
      was related to the extent of the disease. This study was conducted from 2003 to
      2012 with 50 patients diagnosed as having candidemia, that is, 29 with deep
      seated candidiasis and 21 with non-deep-seated candidiasis. The most common
      species recovered from samples obtained from these patients were C. albicans,
      40%; C. tropicalis, 20%; C. parapsilosis, 18%; and C. glabrata, 12%. Serum
      samples were processed according to the manufacturer's recommendations (Vircell
      Microbiologist S.L., Granada, Spain). The CAGTA tests were positive in 1/21 non
      deep-seated candidemias (DSCs; 4.76%) and 20/29 DSCs (68.96%; P < 0.01).
      Accordingly, the values for specificity and positive predictive values of CAGTA
      for identifying DSC were 95%. We concluded that the presence of a positive CAGTA
      test in a sample from a patient with candidemia suggests deep-seated candidiasis.
      Extension screening studies should be considered and origins other than catheters
      should be searched. Prospective studies are needed to determine the clinical
      implications of this finding and its potential use in defining the optimal
      duration of therapy. 

PMID- 24662249
TI  - Prevalence and determinants of parathyroid dysfunction in elderly patients on
      hemodialysis.
AB  - BACKGROUND: The goal of this study was to investigate underlying factors of
      parathyroid dysfunction in elderly patients undergoing maintenance hemodialysis.
      METHODS: A total of 286 patients on maintenance hemodialysis were included.
      Hemoglobin, serum creatinine (Scr), blood urea nitrogen (BUN), serum calcium,
      serum phosphorus (P), intact parathyroid hormone (iPTH), and serum albumin (Alb)
      were measured and analyzed both before and after dialysis. RESULTS: A higher
      incidence of low iPTH level (<150 pg/l) was observed in the elderly group than
      that in the non-elderly group (55.8 vs. 36.7%, p < 0.05). Elderly patients had a
      shorter dialysis duration, lighter dry weight, lower concentrations of BUN, Scr,
      P, iPTH, Alb and standard protein nitrogen present rate (nPNA) compared to that
      of non-elderly group patients (p < 0.05). CONCLUSIONS: Low iPTH level occurs more
      frequently in elderly hemodialysis patients. Furthermore, age, serum P, serum Alb
      and nPNA were independently associated with a low iPTH level.

PMID- 24662253
TI  - How can NSAIDs harm cardiovascular and renal function?
AB  - Consider the potential cardiovascular and renal effects of nonsteroidal anti
      inflammatory drugs when evaluating a patient for short- or long-term use of these
      drugs. Monitoring and extensive counseling is warranted with this particular
      class of medications. 

PMID- 24662254
TI  - Spreading, itchy papules on the extremities.

PMID- 24662256
TI  - Ocular syphilis in a patient with HIV.
AB  - Patients who are HIV-positive and have ocular complaints may have ocular syphilis
      as coinfection with HIV and syphilis is common, and genital ulcerative diseases
      may facilitate HIV infection. Early treatment with IV penicillin can reduce the
      risk of vision loss. 

PMID- 24662257
TI  - Diamond-Blackfan anemia and nutritional deficiency-induced anemia in children.
AB  - Diamond-Blackfan anemia is a rare, inherited disease that characteristically
      presents as a chronic, normochromic macrocytosis due to red cell lineage bone
      marrow failure. Although studies are elaborating on the genetic basis for its
      associated comorbidities, little has been published comparing this anemia to
      other chronic anemias that have similar laboratory results in children. This
      article offers a global perspective of the disease and compares it with anemia
      due to vitamin B12 and folate deficiency in children. 

PMID- 24662258
TI  - The roles of primary care PAs and NPs caring for older adults with diabetes.
AB  - Electronic health record data linked with Medicare data from an academic
      physician group were used to propose a multidimensional characterization of PA
      and NP roles on panels of primary care patients with diabetes. Seven PA and NP
      roles were defined based on level of involvement, visits with complex patients,
      and delivery of chronic care. Findings suggest that PAs and NPs in primary care
      perform a variety of roles and frequently perform multiple roles within a clinic.

PMID- 24662259
TI  - A middle-aged man with a painful toe.

PMID- 24662260
TI  - A young athlete with heel pain.

PMID- 24662261
TI  - After 20 years: leaving a pediatric practice.

PMID- 24662262
TI  - The PDZ-binding domain of syndecan-2 inhibits LFA-1 high-affinity conformation.
AB  - Syndecans are cell membrane proteoglycans that can modulate the activity and
      dynamics of some growth factor receptors and integrins. Here, we show the down
      regulation of integrin lymphocyte function-associated antigen-1 (LFA-1) and
      inhibition of adhesion of Jurkat T cells transfected with syndecan-2. The PDZ
      binding domain in the cytoplasmic region of syndecan-2 was necessary to block the
      LFA-1 high-affinity conformation, and to reduce cellular adhesion. A second
      cytoplasmic motif comprising tyrosines 179 and 191, and serines 187 and 188
      contributed also to reduce LFA-1 function and cellular adhesion. Inhibition of
      the LFA-1 high-affinity conformation by syndecan-2 was independent of the
      expression of the talin head domain and RhoA, Rac1 and Cdc42 GTPases. These
      results demonstrate the importance of PDZ-binding domain of syndecan-2 for
      controlling LFA-1 affinity and cell adhesion.

PMID- 24662263
TI  - Niacin activates the G protein estrogen receptor (GPER)-mediated signalling.
AB  - Nicotinic acid, also known as niacin, is the water soluble vitamin B3 used for
      decades for the treatment of dyslipidemic diseases. Its action is mainly mediated
      by the G protein-coupled receptor (GPR) 109A; however, certain regulatory effects
      on lipid levels occur in a GPR109A-independent manner. The amide form of
      nicotinic acid, named nicotinamide, acts as a vitamin although neither activates
      the GPR109A nor exhibits the pharmacological properties of nicotinic acid. In the
      present study, we demonstrate for the first time that nicotinic acid and
      nicotinamide bind to and activate the GPER-mediated signalling in breast cancer
      cells and cancer-associated fibroblasts (CAFs). In particular, we show that both
      molecules are able to promote the up-regulation of well established GPER target
      genes through the EGFR/ERK transduction pathway. As a biological counterpart,
      nicotinic acid and nicotinamide induce proliferative and migratory effects in
      breast cancer cells and CAFs in a GPER-dependent fashion. Moreover, nicotinic
      acid prevents the up-regulation of ICAM-1 triggered by the pro-inflammatory
      cytokine TNF-alpha and stimulates the formation of endothelial tubes through GPER
      in HUVECs. Together, our findings concerning the agonist activity for GPER
      displayed by both nicotinic acid and nicotinamide broaden the mechanisms involved
      in the biological action of these molecules and further support the potential of
      a ligand to induce different responses mediated in a promiscuous manner by
      distinct GPCRs.

PMID- 24662265
TI  - Efficacy and Toxicity of Every 2 Weeks Docetaxel Regimen in Comparison With
      Weekly or Every 3 Weeks in Metastatic Prostate Cancer: A Retrospective Analysis.
AB  - OBJECTIVES: The aim of this study was to compare weekly (q1w), 2 weekly (q2w),
      and 3 weekly (q3w) regimens of docetaxel in metastatic castration-resistant
      prostate cancer (CRPC). MATERIALS AND METHODS: We retrospectively studied
      patients treated with q1w, q2w, or q3w docetaxel regimens at 30, 60, and 75 mg/m,
      respectively. The choice and duration of treatment was decided by their
      oncologist. Patients were assessed for response, progression-free survival (PFS),
      and overall survival (OS), and toxicity. RESULTS: Twelve, 14, and 15 patients
      were in the q1w, q2w, and q3w arms, respectively. Patients' age, metastases, and
      mean prostate-specific antigen at start and nadir were similar among groups. Mean
      total dose (MTD) was higher (not significantly) in the q2w group. Response rates,
      mean, and median PFS and OS ranked q2w>q3w>q1w (not significantly). However,
      hazard ratios for PFS for the q2w and q3w arms were statistically superior to the
      q1w arm when adjusted for age and total dose. The same was true for OS when q3w
      was compared with q1w. There were no significant differences between the q2w and
      q3w arms. Toxicities were not different between any of the arms, save for grade
      1/2 neuropathy (lower in q1w compared with q2w). CONCLUSIONS: The MTD, response
      rates, PFS, and OS in the q1w and q3w arms were similar to published reports.
      Although we had a small number of patients, our findings suggest that both dose
      concentration and total docetaxel dose may be important in the treatment of CRPC
      and q2w dosing is an option in patients intolerant of a higher dose
      concentration.

PMID- 24662264
TI  - p70S6 kinase is a critical node that integrates HER-family and PI3 kinase
      signaling networks.
AB  - Therapies targeting oncogenic drivers rapidly induce compensatory adaptive
      responses that blunt drug effectiveness, contributing to therapeutic resistance.
      Adaptive responses are characteristic of robust cell signaling networks, and thus
      there is increasing interest in drug combinations that co-target the driver and
      the adaptive response. An alternative approach to co-inhibiting oncogenic and
      adaptive targets is to identify a critical node where the activities of these
      targets converge. Nodes of convergence between signaling modules represent
      potential therapeutic vulnerabilities because their inhibition could result in
      the collapse of the network, leading to enhanced cytotoxicity. In this report we
      demonstrate that p70S6 kinase (p70S6K) can function as a critical node linking
      HER-family and phosphoinositide-3-kinase (PI3K) pathway signaling. We used high
      throughput combinatorial drug screening to identify adaptive survival responses
      to targeted therapies, and found that HER-family and PI3K represented
      compensatory signaling pathways. Co-targeting these pathways with drug
      combinations caused synergistic cytotoxicity in cases where inhibition of neither
      target was effective as a monotherapy. We utilized Reverse Phase Protein Arrays
      and determined that phosphorylation of ribosomal protein S6 was synergistically
      down-regulated upon HER-family and PI3K/mammalian target of rapamycin (mTOR) co
      inhibition. Expression of constitutively active p70S6K protected against
      apoptosis induced by combined HER-family and PI3K/mTOR inhibition. Direct
      inhibition of p70S6K with small molecule inhibitors phenocopied HER-family and
      PI3K/mTOR co-inhibition. These data implicate p70S6K as a critical node in the
      HER-family/PI3K signaling network. The ability of direct inhibitors of p70S6K to
      phenocopy co-inhibition of two upstream signaling targets indicates that
      identification and targeting of critical nodes can overcome adaptive resistance
      to targeted therapies. 

PMID- 24662266
TI  - Phase II Study of Neoadjuvant Chemotherapy With S-1 and CDDP in Patients With
      Lymph Node Metastatic Stage II or III Gastric Cancer.
AB  - OBJECTIVES: We conducted a phase II trial to investigate the efficacy and safety
      of neoadjuvant chemotherapy (NAC) comprising S-1 and cisplatin (CDDP) followed by
      extensive resection in the management of resectable locally advanced gastric
      cancer with lymph node (LN) metastases. METHODS: Patients with LN metastases from
      stage II or III gastric cancer received S-1 and CDDP, as NAC criteria for LN
      metastases were the involvement of >=4 nodes <2 cm or >=1 nodes >=2 cm as
      confirmed by a total body computed tomography scan. All patients underwent
      extensive resection including D2 gastrectomy. The primary endpoint was complete
      resection rate and the secondary endpoints were 3-year relapse-free and overall
      survival. RESULTS: Fifty patients were assessable for the analysis. The complete
      resection rate was 87.8%. Three-year relapse-free survival was 44.9% and 3-year
      overall survival rate was 48.0%. CONCLUSIONS: NAC with S-1 and CDDP is safe and
      may improve the complete resection rate in patients with metastatic LN gastric
      cancer. This suggests that LN metastases would provide good target lesions in
      future clinical trials of NAC.

PMID- 24662267
TI  - Clinicopathologic Features and Outcome of Young Adults With Stage IV Colorectal
      Cancer.
AB  - PURPOSE: Colorectal cancer has a distinct clinicopathologic presentation in
      younger patients. The aim of this paper was to evaluate the outcome of younger
      (age below 50 y) and older patients with stage IV (advanced) colorectal cancer in
      the modern era of combination chemotherapy. METHODS: Cases of metastatic
      colorectal cancer reported in Surveillance, Epidemiology, and End Results
      registry (1973 to 2008) were reviewed. Demographics, tumor characteristics, and
      overall and cancer-specific survivals in patients below 50 and above 50 years of
      age were compared by Cox proportional hazard analyses. Joinpoint regression
      analysis was used to evaluate secular trends in 2-year survival. RESULTS: Younger
      patients had a greater proportion of negative clinicopathologic features (male
      sex, African American ethnicity, and signet ring or mucinous histology). In
      multivariate analysis, older age, male sex, African American ethnicity, right
      sided tumors, and signet ring histology were associated with higher mortality
      risk. Younger patients had improved survival (hazard ratio 0.72; 95% confidence
      interval: 0.70-0.75) compared with older patients, whereas all patients
      experienced increased 2-year survival by joinpoint analysis beginning in 1999
      2000. CONCLUSIONS: The results confirm decreased mortality from advanced
      colorectal cancer in the era of modern combination chemotherapy in younger and
      older patients. Younger age, non-right-sided tumors, and absence of signet ring
      histology significantly associate with better survival.

PMID- 24662268
TI  - D-dimers revisited: a new marker of pancreatic cancer.

PMID- 24662269
TI  - Activity of olive leaf extracts against the promastigote stage of Leishmania
      species and their correlation with the antioxidant activity.
AB  - Leishmaniasis is one of the neglected tropical diseases in terms of drug
      discovery and development. Furthermore, the chemotherapy used to treat this
      disease has been proved to be highly toxic and to present resistance issues. As
      consequent, the need for novel leishmanicidal molecules has notably increased in
      the recent years. In the present work an attempt was made to evaluate the
      antioxidant and leishmanicidal activities besides presence of compounds in leaf
      extracts of 5 different Tunisian olive tree varieties, used as traditional
      medicine in this country. The concentration of extracts needed to inhibit 50% of
      the parasitic growth (IC50) was estimated using different Leishmania strains. All
      tested extracts showed an inhibitory effect on the parasite growth with IC50
      ranging from 2.130+/-0.023 to 71.570+/-4.324MUg/ml, respectively for the
      methanolic extracts of Limouni and Zarrazi against Leishmania donovani. In fact,
      this activity was significantly affected by the olive cultivar and the tested
      Leishmania strain. Furthermore, the activities against both Leishmania tropica
      and major species were correlated to the total phenolic compounds. These results
      could suggest that olive leaf extract could carry potential new compounds for the
      development of novel drugs against Leishmaniasis. 

PMID- 24662270
TI  - The effect of ammonium chloride and urea application on soil bacterial
      communities closely related to the reductive transformation of pentachlorophenol.
AB  - Pentachlorophenol (PCP) is widely distributed in the soil, and nitrogen
      fertilizer is extensively used in agricultural production. However, studies on
      the fate of organic contaminants as affected by nitrogen fertilizer application
      have been rare and superficial. The present study aimed to examine the effect of
      ammonium chloride (NH4Cl) and urea (CO(NH2)2) application on the reductive
      transformation of PCP in a paddy soil. The study showed that the addition of low
      concentrations of NH4Cl/CO(NH2)2 enhanced the transformation of PCP, while the
      addition of high concentrations of NH4Cl/CO(NH2)2 had the opposite effect. The
      variations in the abundance of soil microbes in response to NH4Cl/CO(NH2)2
      addition showed that both NH4Cl and CO(NH2)2 had inhibitory effects on the growth
      of dissimilatory iron-reducing bacteria (DIRB) of the genus Comamonas. In
      contrast, for the genus Shewanella, low concentrations of NH4Cl inhibited growth,
      and high concentrations of NH4Cl enhanced growth, whereas all concentrations of
      CO(NH2)2 showed enhancement effects. In addition, consistent patterns of
      variation were found between the abundances of dechlorinating bacteria in the
      genus Dehalobacter and PCP transformation rates under NH4Cl/CO(NH2)2 addition. In
      conclusion, nitrogen application produced variations in the structure of the soil
      microbial community, especially in the abundance of dissimilatory iron-reducing
      bacteria and dechlorinating bacteria, which, in turn, affected PCP
      dechlorination. 

PMID- 24662271
TI  - Chronic kidney disease and the aging population.

PMID- 24662273
TI  - Screening drug target proteins based on sequence information.
AB  - Identifying new drug target (DT) proteins is important in pharmaceutical and
      biomedical research. General machine learning method (GMLM) classifiers perform
      fairly well at prediction if the training dataset is well prepared. However, a
      common problem in preparing the training dataset is the lack of a negative
      dataset. To address this problem, we proposed two methods that can help GMLM
      better select the negative training dataset from the test dataset. The prediction
      accuracy was improved with the training dataset from the proposed strategies. The
      classifier identified 1797 and 227 potential DT proteins, some of which were
      mentioned in previous research, which added correlative weight to the new method.
      Practically, these two sets of potential DT proteins or their homologues are
      worth considering. 

PMID- 24662272
TI  - Synthesis and Preliminary Evaluation of a 2-Oxoquinoline Carboxylic Acid
      Derivative for PET Imaging the Cannabinoid Type 2 Receptor.
AB  - Cannabinoid receptor subtype 2 (CB2) has been shown to be up-regulated in
      activated microglia and therefore plays an important role in neuroinflammatory
      and neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral
      sclerosis and Alzheimer's disease. The CB2 receptor is therefore considered as a
      very promising target for therapeutic approaches as well as for imaging. A
      promising 2-oxoquinoline derivative designated KP23 was synthesized and
      radiolabeled and its potential as a ligand for PET imaging the CB2 receptor was
      evaluated. [11C]KP23 was obtained in 10%-25% radiochemical yield (decay
      corrected) and 99% radiochemical purity. It showed high stability in phosphate
      buffer, rat and mouse plasma. In vitro autoradiography of rat and mouse spleen
      slices, as spleen expresses a high physiological expression of CB2 receptors,
      demonstrated that [11C]KP23 exhibits specific binding towards CB2. High spleen
      uptake of [11C]KP23 was observed in dynamic in vivo PET studies with Wistar rats.
      In conclusion, [11C]KP23 showed promising in vitro and in vivo characteristics.
      Further evaluation with diseased animal model which has higher CB2 expression
      levels in the brain is warranted. 

PMID- 24662274
TI  - A medical diagnostic tool based on radial basis function classifiers and
      evolutionary simulated annealing.
AB  - OBJECTIVE: The profusion of data accumulating in the form of medical records
      could be of great help for developing medical decision support systems. The
      objective of this paper is to present a methodology for designing data-driven
      medical diagnostic tools, based on neural network classifiers. METHODS: The
      proposed approach adopts the radial basis function (RBF) neural network
      architecture and the non-symmetric fuzzy means (NSFM) training algorithm, which
      presents certain advantages including better approximation capabilities and
      shorter computational times. The novelty in this work consists of adapting the
      NSFM algorithm to train RBF classifiers, and suitably tailoring the evolutionary
      simulated annealing (ESA) technique to optimize the produced RBF models. The
      integration of ESA is critical as it helps the optimization procedure to escape
      from local minima, which could arise from the application of the traditional
      simulated annealing algorithm, and thus discover improved solutions. The
      resulting method is evaluated in nine different medical benchmark datasets, where
      the common objective is to train a suitable classifier. The evaluation includes a
      comparison with two different schemes for training classifiers, including a
      standard RBF training technique and support vector machines (SVMs). Accuracy% and
      the Matthews Correlation Coefficient (MCC) are used for comparing the performance
      of the three classifiers. RESULTS: Results show that the use of ESA helps to
      greatly improve the performance of the NSFM algorithm and provide satisfactory
      classification accuracy. In almost all benchmark datasets, the best solution
      found by the ESA-NSFM algorithm outperforms the results produced by the SFM
      algorithm and SVMs, considering either the accuracy% or the MCC criterion.
      Furthermore, in the majority of datasets, the average solution of the ESA-NSFM
      population is statistically significantly higher in terms of accuracy% and MCC at
      the 95% confidence level, compared to the global optimum solution that its rivals
      could achieve. As far as computational times are concerned, the proposed approach
      was found to be faster compared to SVMs. CONCLUSIONS: The results of this study
      suggest that the ESA-NSFM algorithm can form the basis of a generic method for
      knowledge extraction from data originating from different kinds of medical
      records. Testing the proposed approach on a number of benchmark datasets,
      indicates that it provides increased diagnostic accuracy in comparison with two
      different classifier training methods.

PMID- 24662275
TI  - IBS. Role of sodium channels in IBS.

PMID- 24662276
TI  - Regenerative medicine. Knocking on the door to successful hepatocyte
      transplantation.
AB  - With the ongoing shortage of livers available for transplantation, attention has
      turned to cell-based approaches to support liver function and enable liver
      regeneration. However, hepatocyte transplantation is beset with problems and a
      clinically adoptable strategy is lacking. How can a plentiful supply of
      hepatocyte-like cells with long-term proliferation be generated?

PMID- 24662277
TI  - IBD. Understanding gut microbiota in new-onset Crohn's disease.

PMID- 24662278
TI  - MRI for assessing and predicting response to neoadjuvant treatment in rectal
      cancer.
AB  - Guidelines recommend MRI as part of the staging work-up of patients with rectal
      cancer because it can identify high-risk groups requiring preoperative treatment.
      Phenomenal tumour responses have been observed with current chemoradiotherapy
      regimens-even complete regression in 25% of patients. For these patients, the
      options of organ-saving treatment as an alternative to surgery are now discussed,
      and critical for this approach is the availability of tools that can accurately
      measure response. The value of MRI in rectal cancer staging is established, but
      the role of MRI for the selection of patients for organ-saving treatment is
      debatable, because MRI is not able to accurately assess tumour response to
      preoperative chemoradiotherapy (owing to its reliance on morphological changes).
      Functional MRI is emerging in the field of oncology. It combines information on
      detailed anatomy with that of tumour biology, providing comprehensive information
      on tumour heterogeneity and its changes as a result of treatment. This Review
      provides knowledge on the strengths and weaknesses of MRI for response assessment
      after chemoradiotherapy in rectal cancer and on its ability to predict tumour
      response at the time of primary diagnosis. It elaborates on new functional
      magnetic resonance technology and discusses whether this and new postprocessing
      approaches have the potential to improve prediction and assessment of response. 

PMID- 24662279
TI  - Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy.
AB  - Chronic diarrhoea induced by bile acids is common and the underlying mechanisms
      are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast
      growth factor 19 (FGF19). Increasing evidence, including that from several large
      case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis,
      indicates that bile acid diarrhoea (BAD) accounts for a sizeable proportion of
      patients who would otherwise be diagnosed with IBS. Studies of other approaches
      for diagnosis of BAD have shown increased bile acid synthesis, increased faecal
      levels of primary bile acids, dysbiosis and different urinary volatile organic
      compounds when compared with healthy controls or with other diseases. The role of
      the ileal hormone FGF19 in BAD has been strengthened: a prospective clinical
      study has confirmed low FGF19 levels in BAD, and so a test to measure these
      levels could be developed for diagnosis. In animal models, FGF19 depletion by
      antibodies produces severe diarrhoea. Bile acids affect colonic function through
      farnesoid X receptor (FXR) and TGR5 receptors. As well as these effects in the
      colon, FXR-dependent stimulation of ileal FGF19 production could be a logical
      mechanism to provide therapeutic benefit in BAD. Further studies of FGF19 in
      humans hold promise in providing novel treatments for this cause of chronic
      diarrhoea. 

PMID- 24662280
TI  - GERD. Imaging reveals structural abnormalities in patients with GERD.

PMID- 24662281
TI  - Treatment options for acute pancreatitis.
AB  - This Review covers the latest developments in the treatment of acute
      pancreatitis. The Atlanta Classification of acute pancreatitis has been revised,
      proposing several new terms and abandoning some of the old and confusing
      terminology. The 2012 Revised Atlanta Classification and the determinant-based
      classification aim to universally define the different local and systemic
      complications and predict outcome. The most important differences between these
      classifications are discussed. Several promising treatment options for the early
      management of acute pancreatitis have been tested, including the use of enteral
      nutrition and antibiotics as well as novel therapies such as haemofiltration and
      protease inhibitors. The results are summarized and the quality of evidence is
      discussed. Finally, new developments in the management of patients with infected
      pancreatic necrosis are addressed, including the use of the 'step-up approach'
      and results of minimally invasive necrosectomy. 

PMID- 24662283
TI  - The Cost Effectiveness of Polyetheretheketone (PEEK) Cages for Anterior Cervical
      Discectomy and Fusion.
AB  - STUDY DESIGN: Cost-effectiveness analysis using a Markov model with inputs from
      published literature. OBJECTIVE: To learn which graft or hardware option used in
      a single-level anterior cervical discectomy and fusion (ACDF) is most beneficial
      in terms of cost, quality of life, and overall cost effectiveness. Options
      studied were autograft, allograft, and polyetheretherketone (PEEK) cages for
      cervical fusion. SUMMARY OF BACKGROUND DATA: ACDF is commonly used to treat
      cervical myelopathy and/or radiculopathy. No study has compared the cost
      effectiveness of autograft, allograft, and PEEK in 1-level ACDF. MATERIALS AND
      METHODS: A literature review provided inputs into a Markov decision model to
      determine the most effective graft or hardware option for 1-level ACDF. Data
      regarding rate of complications, quality-adjusted life years (QALYs) gained, and
      cost for each procedure type was collected. The Markov model was first run in a
      base case, using all currently available data. The model was then tested using 1
      way and 2-way sensitivity analyses to determine the validity of the model's
      conclusions if specific aspects of model were changed. This model was run for 10
      years postoperatively. RESULTS: The cost per QALY for each option in the base
      case analysis was $3328/QALY for PEEK, $2492/QALY for autograft, and $2492/QALY
      for allograft. All graft/hardware options are cost effective ways to improve
      outcomes for patients living with chronic neck pain. For graft/hardware options
      the most cost-effective option was allograft. The incremental cost-effectiveness
      ratio for PEEK compared with autograft or allograft was >$100,000/QALY.
      CONCLUSIONS: Allograft is the most cost-effective graft/hardware option for ACDF.
      Compared with living with cervical myelopathy and/or radiculopathy, ACDF using
      any graft or hardware option is a cost-effective method of improving the quality
      of life of patients. PEEK is not a cost-effective option compared with allograft
      or autograft for use in ACDF.

PMID- 24662282
TI  - Activation of the mitochondrial unfolded protein response does not predict
      longevity in Caenorhabditis elegans.
AB  - Recent studies have propagated the model that the mitochondrial unfolded protein
      response (UPR(mt)) is causal for lifespan extension from inhibition of the
      electron transport chain (ETC) in Caenorhabditis elegans. Here we report a genome
      wide RNAi screen for negative regulators of the UPR(mt). Lifespan analysis of
      nineteen RNAi clones that induce the hsp-6p::gfp reporter demonstrate
      differential effects on longevity. Deletion of atfs-1, which is required for
      induction of the UPR(mt), fails to prevent lifespan extension from knockdown of
      two genes identified in our screen or following knockdown of the ETC gene cco-1.
      RNAi knockdown of atfs-1 also has no effect on lifespan extension caused by
      mutation of the ETC gene isp-1. Constitutive activation of the UPR(mt) by gain of
      function mutations in atfs-1 fails to extend lifespan. These observations
      identify several new factors that promote mitochondrial homoeostasis and
      demonstrate that the UPR(mt), as currently defined, is neither necessary nor
      sufficient for lifespan extension. 

PMID- 24662284
TI  - Do Intraoperative LIV-Tilt and Disk Angle Remain Stable at 2-year Follow-up
      Compared With Upright Radiographs in Patients With Idiopathic Scoliosis?: A
      Retrospective Cohort Study.
AB  - STUDY DESIGN: This study was a retrospective chart and radiographic review.
      OBJECTIVE: The aim of this study was to determine if lowest instrumented vertebra
      (LIV) tilt and disk wedging measured intraoperatively correlated to their
      respective values on standing radiographs at intermediate follow-up. SUMMARY OF
      BACKGROUND DATA: No guidelines exist regarding an acceptable intraoperative LIV
      tilt. MATERIALS AND METHODS: After IRB approval, a consecutive series of patients
      with adolescent idiopathic scoliosis (AIS) and structural lumbar curves treated
      with posterior spinal fusion (PSF) at a single institution between 2007 and 2010
      was identified. A total of 163 patients with AIS underwent PSF during this time
      period. Seventeen patients had fusion of structural lumbar curves with adequate
      imaging and a minimum 2-year follow-up. The LIV-tilt and disk angle below the LIV
      was measured on the preoperative standing, intraoperative supine fluoroscopy and
      postoperative standing radiographs, and coronal balance was measured on the
      preoperative and postoperative standing radiographs using a standardized method
      separately by 2 authors. RESULTS: The curve distribution was as follows: Lenke 3
      (29%), Lenke 5 (47%), and Lenke 6 (24%). There was agreement on radiographic
      measurements between the 2 authors with a correlation coefficient of 0.98 for
      coronal balance, 0.91 for LIV-tilt, and 0.65 for disk angle. LIV-tilt improved
      from 19.4 degrees preoperatively to 3.6 degrees intraoperatively. At minimum 2
      year follow-up, LIV had on average progressed to 8.6 degrees. The disk angle
      improved from 5.4 degrees preoperatively to 2.5 degrees intraoperatively. This
      improvement was maintained at 2 years (2.8 degrees). Coronal balance also
      improved during the postoperative period from 17.9 mm immediately following
      surgery to 11.1 mm at the last follow-up. CONCLUSIONS: Compared with prone
      intraoperative fluoroscopic images, disk wedging below LIV remains stable at 2
      years postsurgery on standing radiographs in patients with AISundergoing PSF,
      including structural lumbar curves, whereas LIV-tilt improvement is not
      maintained. Intraoperative fluoroscopy provides a reliable prediction of disk
      wedging below LIV, 2 years after surgery on standing radiographs.

PMID- 24662288
TI  - Elimination of large uremic toxins by a dialyzer specifically designed for high
      volume convective therapies.
AB  - BACKGROUND: Unlike conventional hemodialysis treatments, which rely almost solely
      on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF)
      allows more efficient removal of higher molecular weight toxins due to convective
      transport mechanisms. To facilitate the removal of these toxins in HDF treatment
      modalities, dialyzers with highly efficient high-flux membranes are necessary.
      This study assessed the large uremic toxin removal ability of a high-flux
      dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies
      compared with a standard high-flux dialyzer (FX 60). METHODS: In an open,
      randomized, cross-over, single-center, controlled, prospective clinical study, 30
      adult chronic hemodialysis patients were treated by post-dilution online HDF with
      the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept
      constant in both study arms. The reduction rate (RR) of blood urea nitrogen,
      phosphate, beta2-microglobulin (beta2-m), myoglobin, prolactin, alpha1
      microglobulin, alpha1-acid glycoprotein, albumin and total protein as well as the
      elimination into dialysate was intraindividually compared for the two dialyzer
      types. RESULTS: For FX CorDiax 60 versus FX 60, the RR was significantly higher
      for blood urea nitrogen (86.23 +/- 4.14 vs. 84.89 +/- 4.59%, p = 0.015), beta2-m
      (84.67 +/- 3.79 vs. 81.30 +/- 4.82%, p < 0.0001), myoglobin (75.23 +/- 10.48 vs.
      58.60 +/- 12.1%, p < 0.0001), prolactin (72.96 +/- 9.68 vs. 56.91 +/- 13.01%, p <
      0.0001) and alpha1-microglobulin (20.89 +/- 18.27 vs. 13.60 +/- 12.50%, p =
      0.016). There were no significant differences in the RR for phosphate, alpha1
      acid glycoprotein, albumin and total protein. Mass removal was significantly
      higher with the FX CorDiax 60 than with the FX 60 for beta2-m (0.26 +/- 0.09 vs.
      0.24 +/- 0.09 g, p = 0.0006), myoglobin (1.83 +/- 0.89 vs. 1.51 +/- 0.76 mg, p =
      0.0017), prolactin (0.17 +/- 0.13 vs. 0.14 +/- 0.08 mg, p = 0.02) and albumin
      (4.25 +/- 3.49 vs. 3.01 +/- 2.37 g, p = 0.03). CONCLUSIONS: This study
      demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60
      dialyzer in post-dilution HDF mode significantly increases the elimination of
      middle molecules.

PMID- 24662289
TI  - ADAM10 is the major sheddase responsible for the release of membrane-associated
      meprin A.
AB  - Meprin A, composed of alpha and beta subunits, is a membrane-bound
      metalloproteinase in renal proximal tubules. Meprin A plays an important role in
      tubular epithelial cell injury during acute kidney injury (AKI). The present
      study demonstrated that during ischemia-reperfusion-induced AKI, meprin A was
      shed from proximal tubule membranes, as evident from its redistribution toward
      the basolateral side, proteolytic processing in the membranes, and excretion in
      the urine. To identify the proteolytic enzyme responsible for shedding of meprin
      A, we generated stable HEK cell lines expressing meprin beta alone and both
      meprin alpha and meprin beta for the expression of meprin A. Phorbol 12-myristate
      13-acetate and ionomycin stimulated ectodomain shedding of meprin beta and meprin
      A. Among the inhibitors of various proteases, the broad spectrum inhibitor of the
      ADAM family of proteases, tumor necrosis factor-alpha protease inhibitor (TAPI
      1), was most effective in preventing constitutive, phorbol 12-myristate 13
      acetate-, and ionomycin-stimulated shedding of meprin beta and meprin A in the
      medium of both transfectants. The use of differential inhibitors for ADAM10 and
      ADAM17 indicated that ADAM10 inhibition is sufficient to block shedding. In
      agreement with these results, small interfering RNA to ADAM10 but not to ADAM9 or
      ADAM17 inhibited meprin beta and meprin A shedding. Furthermore, overexpression
      of ADAM10 resulted in enhanced shedding of meprin beta from both transfectants.
      Our studies demonstrate that ADAM10 is the major ADAM metalloproteinase
      responsible for the constitutive and stimulated shedding of meprin beta and
      meprin A. These studies further suggest that inhibiting ADAM 10 activity could be
      of therapeutic benefit in AKI. 

PMID- 24662290
TI  - A dityrosine network mediated by dual oxidase and peroxidase influences the
      persistence of Lyme disease pathogens within the vector.
AB  - Ixodes scapularis ticks transmit a wide array of human and animal pathogens
      including Borrelia burgdorferi; however, how tick immune components influence the
      persistence of invading pathogens remains unknown. As originally demonstrated in
      Caenorhabditis elegans and later in Anopheles gambiae, we show here that an
      acellular gut barrier, resulting from the tyrosine cross-linking of the
      extracellular matrix, also exists in I. scapularis ticks. This dityrosine network
      (DTN) is dependent upon a dual oxidase (Duox), which is a member of the NADPH
      oxidase family. The Ixodes genome encodes for a single Duox and at least 16
      potential peroxidase proteins, one of which, annotated as ISCW017368, together
      with Duox has been found to be indispensible for DTN formation. This barrier
      influences pathogen survival in the gut, as an impaired DTN in Doux knockdown or
      in specific peroxidase knockdown ticks, results in reduced levels of B.
      burgdorferi persistence within ticks. Absence of a complete DTN formation in
      knockdown ticks leads to the activation of specific tick innate immune pathway
      genes that potentially resulted in the reduction of spirochete levels. Together,
      these results highlighted the evolution of the DTN in a diverse set of arthropod
      vectors, including ticks, and its role in protecting invading pathogens like B.
      burgdorferi. Further understanding of the molecular basis of tick innate immune
      responses, vector-pathogen interaction, and their contributions in microbial
      persistence may help the development of new targets for disrupting the pathogen
      life cycle. 

PMID- 24662291
TI  - Syntenin-1 and ezrin proteins link activated leukocyte cell adhesion molecule to
      the actin cytoskeleton.
AB  - Activated leukocyte cell adhesion molecule (ALCAM) is a type I transmembrane
      protein member of the immunoglobulin superfamily of cell adhesion molecules.
      Involved in important pathophysiological processes such as the immune response,
      cancer metastasis, and neuronal development, ALCAM undergoes both homotypic
      interactions with other ALCAM molecules and heterotypic interactions with the
      surface receptor CD6 expressed at the T cell surface. Despite biochemical and
      biophysical evidence of a dynamic association between ALCAM and the actin
      cytoskeleton, no detailed information is available about how this association
      occurs at the molecular level. Here, we exploit a combination of complementary
      microscopy techniques, including FRET detected by fluorescence lifetime imaging
      microscopy and single-cell force spectroscopy, and we demonstrate the existence
      of a preformed ligand-independent supramolecular complex where ALCAM stably
      interacts with actin by binding to syntenin-1 and ezrin. Interaction with the
      ligand CD6 further enhances these multiple interactions. Altogether, our results
      propose a novel biophysical framework to understand the stabilizing role of the
      ALCAM supramolecular complex engaged to CD6 during dendritic cell-T cell
      interactions and provide novel information on the molecular players involved in
      the formation and signaling of the immunological synapse at the dendritic cell
      side. 

PMID- 24662292
TI  - Distinct modes of ubiquitination of peroxisome-targeting signal type 1 (PTS1)
      receptor Pex5p regulate PTS1 protein import.
AB  - Peroxisome targeting signal type-1 (PTS1) receptor, Pex5p, is a key player in
      peroxisomal matrix protein import. Pex5p recognizes PTS1 cargoes in the cytosol,
      targets peroxisomes, translocates across the membrane, unloads the cargoes, and
      shuttles back to the cytosol. Ubiquitination of Pex5p at a conserved cysteine is
      required for the exit from peroxisomes. However, any potential ubiquitin ligase
      (E3) remains unidentified in mammals. Here, we establish an in vitro
      ubiquitination assay system and demonstrate that RING finger Pex10p functions as
      an E3 with an E2, UbcH5C. The E3 activity of Pex10p is essential for its
      peroxisome-restoring activity, being enhanced by another RING peroxin, Pex12p.
      The Pex10p.Pex12p complex catalyzes monoubiquitination of Pex5p at one of
      multiple lysine residues in vitro, following the dissociation of Pex5p from
      Pex14p and the PTS1 cargo. Several lines of evidence with lysine-to-arginine
      mutants of Pex5p demonstrate that Pex10p RING E3-mediated ubiquitination of Pex5p
      is required for its efficient export from peroxisomes to the cytosol and
      peroxisomal matrix protein import. RING peroxins are required for both modes of
      Pex5p ubiquitination, thus playing a pivotal role in Pex5p shuttling. 

PMID- 24662293
TI  - Inactivation of C/ebp homologous protein-driven immune-metabolic interactions
      exacerbate obesity and adipose tissue leukocytosis.
AB  - Successful adaptation to periods of chronic caloric excess is a highly
      coordinated event that is critical to the survival and propagation of species.
      Transcription factor C/ebp homologous protein (Chop) is thought to be an
      important molecular mediator that integrates nutrient signals to endoplasmic
      reticulum (ER) stress and innate immune activation. Given that aberrant ER stress
      response is implicated in inducing metabolic inflammation and insulin resistance,
      we hypothesized that ER stress target gene Chop integrates immune and metabolic
      systems to adapt to chronic positive energy balance. Here we report that
      inactivation of Chop in mice fed a high fat diet led to significant increase in
      obesity caused by a reduction in energy expenditure without any change in food
      intake. Importantly, ablation of Chop does not induce metabolically healthy
      obesity, because Chop-deficient mice fed a high fat diet had increased hepatic
      steatosis with significantly higher insulin resistance. Quantification of adipose
      tissue leukocytosis revealed that elimination of Chop during obesity led to
      substantial increase in number of adipose tissue T and B lymphocytes. In
      addition, deficiency of Chop led to increase in total number of myeloid
      subpopulations like neutrophils and F4/80(+) adipose tissue macrophages without
      any alterations in the frequency of M1- or M2-like adipose tissue macrophages.
      Further investigation of inflammatory mechanisms revealed that ablation of Chop
      increases the sensitivity of macrophages to inflammasome-induced activation of IL
      beta in macrophages. Our findings indicate that regulated expression of Chop
      during obesity is critical for adaptation to chronic caloric excess and
      maintenance of energy homeostasis via integration of metabolic and immune
      systems. 

PMID- 24662294
TI  - Interleukin-1 receptor-associated kinase-2 genetic variant rs708035 increases NF
      kappaB activity through promoting TRAF6 ubiquitination.
AB  - The IL-1 receptor-associated kinases (IRAKs) are key regulators of Toll-like
      receptor (TLR)/IL-1 signaling, which are critical regulators of mammalian
      inflammation and innate immune response. Single nucleotide polymorphisms (SNPs)
      within the IRAK genes have been discovered recently. However, the functions of
      these IRAK SNPs remain largely unknown. Here, we found that the non-synonymous
      IRAK2 variant rs708035 (coding D431E) increases NF-kappaB activity and leads to
      more expression of NF-kappaB-dependent proinflammatory cytokines compared with
      IRAK2 wild type. Moreover, when IRAK2 knockdown cells reconstituted with siRNA
      resistant WT-IRAK2 or D431E-IRAK2 were infected with influenza virus, a more
      obvious induction of IL-6 and a stronger anti-apoptosis effect were observed in
      D431E-IRAK2 expressing cells. Notably, we also found that the levels of
      proinflammatory cytokine-IL-6 were indeed higher in people carrying D431E-IRAK2
      than those carrying WT-IRAK2. Further study demonstrated that elevated NF-kappaB
      activation mediated by the IRAK2 variant was due to increased TRAF6
      ubiquitination and faster IkappaBalpha degradation. Our study provides important
      insight of IRAK2 SNP in the regulation of NF-kappaB activation and indicates that
      IRAK2 rs708035 might be associated with human diseases caused by hyper-activation
      of NF-kappaB. 

PMID- 24662296
TI  - Growth and HIV-free survival of HIV-exposed infants in Malawi: a randomized trial
      of two complementary feeding interventions in the context of maternal
      antiretroviral therapy.
AB  - OBJECTIVE: To compare the growth of HIV-exposed children receiving 1 of 2
      complementary foods after prevention of mother-to-child HIV transmission through
      maternal lifelong antiretroviral therapy (ART). METHODS: In rural Malawi, 280 HIV
      infected pregnant women were consecutively identified and offered ART, without
      consideration of their CD4 counts. Mothers were supported to exclusively breast
      feed and children tested for HIV status at 1.5 and 5.5 months of age. From this
      group, 248 HIV-exposed children were enrolled and randomized to receive
      micronutrients with either whole milk powder or a ready-to-use complementary food
      (RUF), until the child reached 12 months of age. Children were followed until 18
      months of age. RESULTS: HIV-free survival at 12 months was 90% (95% confidence
      interval: 87% to 94%). Exclusive breast-feeding for the first 6 months of life
      was practiced in 97% of the children. At 12 months of age, 89% of the children
      continued to be breast-fed. At 6 months of age, infants had a weight-for-height z
      score of 0.7 +/- 1.1 (mean +/- SD) and length-for-age z score of -1.3 +/- 1.2.
      The decrease in length-for-age z score among children receiving RUF at 12 months
      of age was greater than that seen in those receiving milk powder (-0.3 +/- 0.8 vs
      -0.1 +/- 0.7, P = 0.04). Mean weight-for-height z score was >0 at 12 and 18
      months of age in both groups. CONCLUSIONS: HIV-free survival >=90% at 12 months
      was achieved with maternal ART while either milk powder or RUF as a complementary
      food preserved child anthropometry. Breast-feeding by mothers receiving ART was
      acceptable.

PMID- 24662295
TI  - An omitted level: an examination of relational orientations and viral suppression
      among HIV serodiscordant male couples.
AB  - Couples' adopting a relational orientation, when partners regard themselves as a
      collective unit, is associated with optimal health. HIV-positive men and their
      HIV-negative partners (N = 116 serodiscordant male couples) were surveyed.
      Logistic regression showed greater relational orientations of HIV-positive
      [adjusted odds ratio (aOR) = 7.87; 95% confidence interval (CI): 1.63 to 38.05]
      and HIV-negative partners (aOR = 6.16; 95% CI: 1.43 to 26.59) and HIV-positive
      partners' higher income (aOR = 2.95; 95% CI: 1.13 to 7.70) and lower depression
      (aOR = 0.39; 95% CI: 0.15 to 0.97) were associated with viral suppression with no
      evidence of mediation by adherence. Incorporating relationship dynamics into
      biomedical strategies is a promising avenue for research and intervention.

PMID- 24662297
TI  - Origin and outbreak of HIV-1 CRF55_01B among MSM in Shenzhen, China.

PMID- 24662298
TI  - Stuck in the middle: longitudinal HIV-related health disparities among men who
      have sex with men and women.
AB  - INTRODUCTION: Men who have sex with men and women (MSMW) have been shown in cross
      sectional studies to suffer HIV-related health disparities above and beyond those
      found among men who have sex with men only (MSMO). We conducted a secondary data
      analysis over a 7-year time frame of participants in the Multicenter AIDS Cohort
      Study, a long-standing prospective cohort study, to examine whether MSMW had
      persistently higher rates of depression symptoms, polydrug use, and (among HIV
      positive men who have sex with men) HIV viral load levels compared with MSMO.
      METHODS: Men were behaviorally defined as bisexual if they reported sexual
      activity with at least 1 male and 1 female partner between study waves 38 and 50.
      We used generalized mixed modeling with repeated measures to test differences in
      CES-D score, polydrug use, and viral load between sexually active MSMO (n = 1514)
      and MSMW (n = 111), adjusting for age, income, race/ethnicity, and recent
      seroconversion. RESULTS: MSMW were significantly more likely than MSMO to have
      higher CES-D scores, polydrug use, and viral load levels (all P < 0.01). Outcome
      trajectories did not differ significantly over time between these groups. Black
      and Hispanic HIV-positive MSMW had higher viral load levels relative to white HIV
      positive MSMW (P < 0.01). DISCUSSION: Compared with MSMO, MSMW in the Multicenter
      AIDS Cohort Study suffer from profound and persistent HIV-related health
      disparities across biological, behavioral, and psychosocial domains. Further
      qualitative and quantitative research contextualizing the pathways underlying
      these disparities is recommended for intervention development targeting MSMW at
      risk for HIV acquisition and transmission.

PMID- 24662299
TI  - Factors associated with recurrence of cervical intraepithelial neoplasia 2+ after
      treatment among HIV-infected women in Western Kenya.
AB  - HIV-infected women are at increased risk for recurrence of cervical dysplasia
      after treatment. Short-term recurrence rates may reflect treatment efficacy and
      therefore impact screening protocols and follow-up planning. We conducted a
      prospective study of 297 HIV-infected women undergoing loop electrosurgical
      excision procedure for cervical intraepithelial neoplasia 2+ (CIN2+) in an HIV
      clinic in Kisumu, Kenya. By 6 months after the procedure, 20 (7.1%) of women had
      recurrent CIN2+. Recurrence was significantly associated with CD4 nadir but not
      with highly active antiretroviral therapy use. Longer-term follow-up of this
      cohort will illustrate the potential impact of highly active antiretroviral
      therapy and immune status on CIN2/3 disease recurrence.

PMID- 24662300
TI  - Association between polymorphisms in sclerostin, dickkopfs and secreted frizzled
      related protein genes and bone mineral density in postmenopausal Korean women.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the association
      between single nucleotide polymorphisms (SNPs) in sclerostin (SOST), dickkopf
      (DKK), secreted frizzled-related protein (sFRP) genes and bone mineral density
      (BMD) in postmenopausal Korean women. METHODS: The SOST, Wnt inhibitory factor 1
      (WIF1), sFRP1,sFRP2,sFRP3, sFRP4, sFRP5, DKK1, DKK2 and DKK3 polymorphisms were
      analyzed in 399 postmenopausal Korean women. Serum levels of bone turnover
      markers were measured, and BMDs at the lumbar spine and femoral neck were also
      examined. RESULTS: No significant differences in adjusted BMD at the lumbar spine
      and femoral neck were noted according to any single and combined polymorphisms
      measured in SOST, DKKs and sFRPs. However, osteoporosis at the femoral neck was
      2.35 times more frequently observed in the AA genotype of the sFRP4 c.958C>A
      polymorphism compared to the non-AA genotype (95% CI 1.09-5.08, p = 0.03). Also,
      the CC genotype of the sFRP3 c.970C>G polymorphism had a higher rate of
      osteoporosis at the femoral neck compared to the GC genotype (OR 8.47, 95% CI
      1.37-52.63, p = 0.049). CONCLUSIONS: Our results suggest that the sFRP3 c.970C>G
      and sFRP4 c.958C>A polymorphisms may be genetic factors associated with the
      prevalence of osteoporosis at the femoral neck in postmenopausal Korean women.

PMID- 24662301
TI  - Triple or dual therapy for HCV-1 naive patients? Optimizing selection tools.

PMID- 24662302
TI  - Minimal portal vein stenosis is a promising preconditioning in living donor liver
      transplantation in porcine model.
AB  - BACKGROUND & AIMS: The main hindrance in promoting living donor liver
      transplantation remains the morbi-mortality risk for the donor. Considering the
      opposed remodeling influence of portal and hepatic artery flows, our working
      hypothesis was to identify a lobar portal vein stenosis capable of inducing a
      contralateral liver mass compensatory enlargement, without the downstream
      ipsilateral atrophic response. METHODS: Twenty-four pigs entered this study. Six
      of them were used to establish hemodynamic changes following a progressive left
      portal vein (LPV) stenosis, in blood flow, pressure and vessel diameter of the
      LPV, main portal vein and hepatic artery. Sixteen pigs were divided into 4
      groups: sham operated animals, 20% LPV stenosis, 50% LPV stenosis, and 100% LPV
      stenosis. Daily liver biopsies were collected until post-operative day 5 to
      investigate liver regeneration and atrophy (Ki67, STAT3, LC3, and activated
      caspase 3) according to the degree of LPV stenosis. Finally, changes in liver
      volumetry after 20% LPVS were investigated. RESULTS: A 20% LPV stenosis led to
      dilatation of the hepatic artery and a subsequent four-fold increase in hepatic
      arterial flow. Concomitantly, liver regeneration was triggered in the non-ligated
      lobe and the cell proliferation peak, 5 days after surgery, was comparable to
      that obtained after total LPV ligation. Moreover, 20% LPV stenosis
      preconditioning did not induce left liver atrophy contrary to 50 and 100% LPV
      stenosis. CONCLUSIONS: A 20% LPV stenosis seems to be the adequate
      preconditioning to get the remnant liver of living donor ready to take on graft
      harvesting without atrophy of the future graft.

PMID- 24662303
TI  - Transvaginal evisceration 20 years after hysterectomy. Case report and literature
      review.
AB  - Vaginal evisceration is a rare emergency complication which needs prompt surgical
      treatment. We report a rare case of a seventy-three year old patient presented
      with late onset of transvaginal intestinal evisceration, 20 years after
      hysterectomy. A short review of the literature focused on the last 10 years. The
      laparoscopic approach represents an additional risk factor for evisceration, but
      data are poor, and prospective studies are difficult to perform. The treatment of
      transvaginal evisceration is exclusively surgical, by abdominal, transvaginal or
      combined abdominal-vaginal approaches along with laparoscopy. The abdominal and
      combined vaginal-abdominal approaches, allow a complete inspection of the
      abdominal cavity and to apply a mesh for repairing and preventing recurrences.
      Transvaginal evisceration despite being rare, can still represent a challenging
      problem in emergency for general surgeons and gynecologists. Knowledge of the
      related problems and the surgical approach is mandatory to optimize the outcome.
      KEY WORDS: Evisceration Complication, Mesh repair, Post-hysterectomy.

PMID- 24662304
TI  - Dysregulation of the TGFBI gene is involved in the oncogenic activity of the
      nonsense mutation of hepatitis B virus surface gene sW182*.
AB  - The nonsense mutations of the hepatitis B virus (HBV) surface (S) gene have been
      reported to have oncogenic potential. We have previously identified several
      transforming nonsense mutations of the HBV S gene from hepatocarcinoma (HCC)
      patients. Among them, the sW182* mutant (the stop codon for tryptophan 182)
      showed the most potent oncogenicity in a mouse xenograft model using stably
      transfected mouse fibroblast cells. This study is aimed at understanding the
      molecular mechanisms leading to the oncogenic activity of the sW182* mutant. A
      gene expression microarray in combination with gene set enrichment analysis
      (GSEA) revealed differentially expressed gene sets in the sW182* cells, including
      those related to cell-cycle regulation, deoxyribonucleic acid repair, and genome
      instability. Of the differentially expressed genes, the transforming growth
      factor-beta-induced (TGFBI) gene was further validated to be dysregulated in the
      sW182* cells. This dysregulation was accompanied by hypermethylation of the TGFBI
      promoter. The level of cyclin D1, a negatively regulated TGFBI target, was highly
      elevated in the sW182* mutant cells, which is consistent with the potent
      oncogenicity. Furthermore, frequent abnormal mitosis and multinucleation were
      observed in the mutant cells. Exogenous expression of TGFBI alleviated the
      oncogenic activity of the sW182* cells. In human HBV-related HCC cancerous
      tissue, expression of TGFBI was downregulated in 25 of the 55 (45%) patients
      examined, suggesting that TGFBI dysregulation could occur in HBV-related HCC
      development in some cases. These results suggest that dysregulation of TGFBI is
      involved in the oncogenic activity of the sW182* mutant of the hepatitis B virus
      S gene. 

PMID- 24662305
TI  - Ubiquitin C-terminal hydrolase L1 deletion ameliorates glomerular injury in mice
      with ACTN4-associated focal segmental glomerulosclerosis.
AB  - Renal ubiquitin C-terminal hydrolase L1 (UCHL1) is upregulated in a subset of
      human glomerulopathies, including focal segmental glomerulosclerosis (FSGS),
      where it may serve to promote ubiquitin pools for degradation of cytotoxic
      proteins. In the present study, we tested whether UCHL1 is expressed in podocytes
      of a mouse model of ACTN4-associated FSGS. Podocyte UCHL1 protein was detected in
      glomeruli of K256E-ACTN4(pod+)/UCHL1+/+ mice. UCHL1+/- mice were intercrossed
      with K256E-ACTN4(pod+) mice and monitored for features of glomerular disease. 10
      week-old K256E-ACTN4(pod+)/UCHL1-/- mice exhibited significantly ameliorated
      albuminuria, glomerulosclerosis, tubular pathology and blood pressure.
      Interestingly, while UCHL1 deletion diminished both tubular and glomerular
      apoptosis, WT1-positive nuclei were unchanged. Finally, UCHL1 levels correlated
      positively with poly-ubiquitinated proteins but negatively with K256E-alpha
      actinin-4 levels, implying reduced K256E-alpha-actinin-4 proteolysis in the
      absence of UCHL1. Our data suggest that UCHL1 upregulation in ACTN4-associated
      FSGS fuels the proteasome and that UCHL1 deletion may impair proteolysis and
      thereby preserve K256E/wt-alpha-actinin-4 heterodimers, maintaining podocyte
      cytoskeletal integrity and protecting the glomerular filtration barrier. 

PMID- 24662307
TI  - Joint physical custody, turning to parents for emotional support, and subjective
      health: A study of adolescents in Stockholm, Sweden.
AB  - AIMS: Among children with separated parents, the arrangement of joint physical
      custody, i.e. children living equally much in both parents' homes, has increased
      substantially during the last decades in Sweden. To date, empirical research on
      the living conditions of this group is limited. This study analyses family type
      differences in turning to parents for emotional support and in subjective health
      among adolescents. The focus of the study is adolescents in joint physical
      custody, who are compared with those living with two original parents in the same
      household; those living (only) in a single-parent household; and those living
      (only) in a reconstituted family. METHODS: The data come from the Stockholm
      School Survey of 2004, a total population survey of students in grade 9 (15-16
      years) in Stockholm (n=8,840). Ordinary least squares (OLS) regressions were
      conducted. RESULTS: Turning to both parents about problems is most commonly
      reported by adolescents in intact families, followed by those in joint physical
      custody. Adolescents in non-traditional family types report worse subjective
      health than adolescents in intact families, but the difference is smaller for
      those in joint physical custody than for those living with a single parent. The
      slightly poorer health of adolescents in joint physical custody than those in
      intact families is not explained by their lower use of parents as a source of
      emotional support. CONCLUSIONS: The study suggests that joint physical custody is
      associated with a higher inclination to use parents as a source of emotional
      support and better subjective health than other post-divorce family types.

PMID- 24662306
TI  - Piceatannol attenuates cardiac hypertrophy in an animal model through regulation
      of the expression and binding of the transcription factor GATA binding factor 6.
AB  - Piceatannol is found in grapes, passion fruit, and Japanese knotweed. Piceatannol
      pretreatment suppresses cardiac hypertrophy induced by isoproterenol as assessed
      by heart weight/body weight ratio, cross-sectional area, and expression of
      hypertrophic markers. The anti-hypertrophic effect of piceatannol in rat neonatal
      cardiomyocytes is the same as that in vivo. Piceatannol inhibits lentiviral-GATA6
      induced cardiomyocyte hypertrophy. Furthermore, piceatannol reduces the
      interaction between GATA4 and GATA6 as well as the DNA-binding activity of
      endogenous GATA6 in the ANP promoter. Our results suggest that piceatannol may be
      a novel therapeutic agent for the prevention of cardiac hypertrophy.

PMID- 24662308
TI  - Relationship of SOC with sociodemographic variables, mental disorders and
      mortality.
AB  - BACKGROUND: SOC is associated with wellbeing and health. The Lundby Study is a
      cohort study of an unselected population (n=3563) in whom mental health and
      personality traits have been assessed since 1947, with follow ups in 1957, 1972,
      and 1997. AIM: To describe the relationship of Antonovsky's 29-item sense of
      coherence scale (SOC) and its three subscales (comprehensibility, manageability,
      and meaningfulness) to mental health and mortality in an unselected middle-aged
      and elderly community cohort, controlling for gender, age, marital status, and
      socioeconomic status. Another aim was to analyse the three-factor structure of
      the SOC. METHODS: Of the 1797 surviving subjects in 1997, 1559 participated in a
      semistructured diagnostic interview, and 1164 subjects completed the SOC
      questionnaire. Psychiatrists performed diagnostic evaluations. Collateral
      information was obtained from case notes and registers. Dates of death from 1997
      2011 were obtained from the cause of death register. RESULTS: SOC scores showed
      no sex differences, but were positively correlated with age. SOC scores were
      higher in married relative to unmarried participants and in blue-collar workers
      and self-employed individuals relative to white-collar workers. Total SOC and
      subscale scores were negatively correlated with depressive, anxiety, organic, and
      psychotic disorders. Male gender was positively correlated with comprehensibility
      and female gender was positively correlated with manageability and
      meaningfulness. Higher comprehensibility scores were correlated with lower
      mortality. CONCLUSIONS: SOC scores increased with age, were higher for blue
      collar workers, and were lower for individuals with psychiatric disorders. Higher
      comprehensibility scores were associated with lower mortality. However, there was
      only weak evidence for a three-factor structure.

PMID- 24662310
TI  - Factors influencing the retrograde labeling of retinal ganglion cells with
      fluorogold in an animal optic nerve crush model.
AB  - PURPOSE: To investigate whether different crush durations or a different
      fluorogold (FG) injection timing can affect the efficiency of FG retrograde
      labeling of retinal ganglion cells (RGCs) in the optic nerve (ON) crush model.
      METHODS: We performed the ON crush in rats with a clip at different durations or
      a jewel forceps to compare the effects of different crush methods with FG
      staining. RGC density was compared between the FG injection 1 week before the
      sacrifice of the animals (group A) and the injection before the crush experiment
      (group B). Double staining with CD11b and FG in the retinal sections was
      conducted to investigate the relationship between the overcounting of RGCs and
      microglia. RESULTS: The FG-stained particles were significantly decreased at the
      distal part of the crush site compared to the proximal site of the ON with a
      crush duration of over 30 s or when crushed with the jewel forceps. Two weeks
      after ON crush, the RGC count was higher both in the central and mid-peripheral
      retinas in group B. The percentage of CD11b-stained cells among the FG-stained
      cells in the RGC layer of retinas in group B was higher than that of group A (34%
      in group B vs. 4% in group A, p = 0.0001). Overcounting of RGC density in group B
      was due to additional microglia with FG engulfing. CONCLUSIONS: Our results
      suggest that each laboratory should test its setting conditions to avoid factors
      influencing the RGC density measurement before conducting ON crush experiments.

PMID- 24662309
TI  - Immunomodulatory effects of voriconazole and caspofungin on human peripheral
      blood mononuclear cells stimulated by Candida albicans and Candida krusei.
AB  - BACKGROUND: Candida infections are frequently associated with high morbidity and
      mortality rates in immunosuppressed patients. T cell-mediated and phagocytic
      immunity are the primary protective immune responses against fungal infections.
      Antifungal agents such as voriconazole and caspofungin enter phagocytic cells and
      lead to various intracellular activities. In this study, the authors aimed to
      investigate the immunomodulatory effects of voriconazole and caspofungin on human
      peripheral blood mononuclear cells (PBMC) stimulated by Candida albicans and
      Candida krusei. METHODS: Human PBMC isolation was performed by Ficoll-hypaque
      density-gradient centrifugation method. Cell proliferation was assessed by
      colorimetric method using MTT. The cytokine levels in the human PBMC culture
      supernatants stimulated by C. albicans and C. krusei were determined by enzyme
      linked immunosorbent assay. RESULTS: The addition of voriconazole and caspofungin
      lead to proliferation of PBMC. In the presence of voriconazole and caspofungin,
      the levels of IL-2, IFN-gamma and IL-6 remarkably increased in PBMC stimulated by
      C. albicans and C. krusei. However, the combination of antifungal drugs and PBMC
      stimulated by Candida species did not increase the levels of TGF-beta and IL-10.
      CONCLUSIONS: The results indicate that voriconazole and caspofungin have
      immunomodulatory effects on human PBMC stimulated by Candida species. The
      interaction between antifungal drugs and PBMC stimulates Th1-type cytokine
      secretion. Cytokine stimulation from immune cells can assist in the elimination
      of fungal pathogens. Therefore, during the treatment of fungal infection,
      putative immunomodulatory effects of antifungal agents should be taken into
      account.

PMID- 24662311
TI  - Up-scaling aquaculture wastewater treatment by microalgal bacterial flocs: from
      lab reactors to an outdoor raceway pond.
AB  - Sequencing batch reactors with microalgal bacterial flocs (MaB-floc SBRs) are a
      novel approach for photosynthetic aerated wastewater treatment based on
      bioflocculation. To assess their technical potential for aquaculture wastewater
      treatment in Northwest Europe, MaB-floc SBRs were up-scaled from indoor
      photobioreactors of 4 L over 40 and 400 L to a 12 m(3) outdoor raceway pond.
      Scale-up decreased the nutrient removal efficiencies with a factor 1-3 and the
      volumetric biomass productivities with a factor 10-13. Effluents met current
      discharge norms, except for nitrite and nitrate. Flue gas sparging was needed to
      decrease the effluent pH. Outdoor MaB-flocs showed enhanced settling properties
      and an increased ash and chlorophyll a content. Bioflocculation enabled
      successful harvesting by gravity settling and dewatering by filtering at 150-250
      MUm. Optimisation of nitrogen removal and biomass valorisation are future
      challenges towards industrial implementation of MaB-floc SBRs for aquaculture
      wastewater treatment.

PMID- 24662312
TI  - Use of Empty Fruit Bunches from the oil palm for bioethanol production: a
      thorough comparison between dilute acid and dilute alkali pretreatment.
AB  - In the present work, two pretreatment techniques using either dilute acid (H2SO4)
      or dilute alkali (NaOH) have been compared for producing bioethanol from Empty
      Fruit Bunches (EFBs) from oil palm tree, a relevant feedstock for tropical
      countries. Treatments' performances under different conditions have been assessed
      and statistically optimized with respect to the response upon standardized
      enzymatic saccharification. The dilute acid treatment performed at optimal
      conditions (161.5 degrees C, 9.44 min and 1.51% acid loading) gave 85.5% glucose
      yield, comparable to those of other commonly investigated feedstocks. Besides,
      the possibility of using fibers instead of finely ground biomass may be of
      economic interest. Oppositely, treatment with dilute alkali has shown lower
      performances under the conditions explored, most likely given the relatively
      significant lignin content, suggesting that the use of stronger alkali regime
      (with the associated drawbacks) is unavoidable to improve the performance of this
      treatment.

PMID- 24662313
TI  - Application of a novel enzymatic pretreatment using crude hydrolytic
      extracellular enzyme solution to microalgal biomass for dark fermentative
      hydrogen production.
AB  - In this study, a novel enzymatic pretreatment of Chlorella vulgaris for dark
      fermentative hydrogen production (DFHP) was performed using crude hydrolytic
      extracellular enzyme solution (CHEES) extracted from the H2 fermented effluent of
      food waste. It was found that the enzyme extracted at 52 h had the highest
      hydrolysis efficiency of microalgal biomass, resulting in the highest H2 yield of
      43.1 mL H2/g dry cell weight along with shorter lag periods. Even though a high
      amount of VFAs was accumulated in CHEES, especially butyrate, the fermentative
      bacteria on the DFHP was not affected from product inhibition. It also appears
      that the presence of organic acids, especially lactate and acetate, contained in
      the CHEES facilitated enhancement of H2 production acted as a co-substrate.
      Therefore, all of the experimental results suggest that the enhancement of DFHP
      performance caused by CHEES has a dual role as the hydrolysis enhancer and the co
      substrate supplier.

PMID- 24662315
TI  - An evaluation of intranasal sufentanil and dexmedetomidine for pediatric dental
      sedation.
AB  - Conscious or moderate sedation is routinely used to facilitate the dental care of
      the pre- or un-cooperative child. Dexmedetomidine (DEX) has little respiratory
      depressant effect, possibly making it a safer option when used as an adjunct to
      either opioids or benzodiazepines. Unlike intranasal (IN) midazolam, IN
      application of DEX and sufentanil (SUF) does not appear to cause much discomfort.
      Further, although DEX lacks respiratory depressive effects, it is an alpha2
      agonist that can cause hypotension and bradycardia when given in high doses or
      during prolonged periods of administration. The aim of this feasibility study was
      to prospectively assess IN DEX/SUF as a potential sedation regimen for pediatric
      dental procedures. After IRB approval and informed consent, children (aged 3-7
      years; n = 20) from our dental clinic were recruited. All patients received 2
      MUg/kg (max 40 MUg) of IN DEX 45 min before the procedure, followed 30 min later
      by 1 MUg/kg (max 20 MUg) of IN SUF. An independent observer rated the effects of
      sedation using the Ohio State University Behavior Rating Scale (OSUBRS) and
      University of Michigan Sedation Scale (UMSS). The dentist and the parent also
      assessed the efficacy of sedation. Dental procedures were well tolerated and none
      were aborted. The mean OSUBRS procedure score was 2.1, the UMSS procedure score
      was 1.6, and all scores returned to baseline after the procedure. The average
      dentist rated quality of sedation was 7.6 across the 20 subjects. After
      discharge, parents reported one child with prolonged drowsiness and one child who
      vomited at home. The use of IN DEX supplemented with IN SUF provided both an
      effective and tolerable form of moderate sedation. Although onset and recovery
      are slower than with oral (PO) midazolam and transmucosal fentanyl, the quality
      of the sedation may be better with less risk of respiratory depression. Results
      from this preliminary study showed no major complications from IN delivery of
      these agents. 

PMID- 24662314
TI  - Subviral particle as vaccine and vaccine platform.
AB  - Recombinant subvirual particles retain similar antigenic features of their
      authentic viral capsids and thus have been applied as nonreplicating subunit
      vaccines against viral infection and illness. Additionally, the self-assembled,
      polyvalent subviral particles are excellent platforms to display foreign antigens
      for immune enhancement for vaccine development. These subviral particle-based
      vaccines are noninfectious and thus safer than the conventional live attenuated
      and inactivated vaccines. While several VLP vaccines are available in the
      markets, numerous others, including dual vaccines against more than one pathogen,
      are under clinical or preclinical development. This article provides an update of
      these efforts. 

PMID- 24662317
TI  - NHS hospitals set to make overall loss for first time since 2006.

PMID- 24662316
TI  - Apolipoprotein E-deficient mice are susceptible to the development of acute lung
      injury.
AB  - BACKGROUND: Apolipoprotein E (apoE) has been shown to play a pivotal role in the
      development of cardiovascular disease, attributable to its function in lipid
      trafficking and immune modulating properties; however, its role in modulating
      inflammation in the setting of acute lung injury (ALI) is unknown. OBJECTIVE: To
      determine whether apoE-deficient mice (apoE-/-) are more susceptible to ALI
      compared to wild-type (WT) animals. METHODS: Two independent models of ALI were
      employed. Firstly, WT and apoE-/- mice were randomized to acid aspiration (50 MUl
      of 0.1 N hydrochloric acid) followed by 4 h of mechanical ventilation. Secondly,
      WT and apoE-/- mice were randomized to 72 h of hyperoxia exposure or room air.
      Thereafter, the intrinsic responses of WT and apoE-/- mice were assessed using
      the isolated perfused mouse lung (IPML) setup. Finally, based on elevated levels
      of oxidized low-density lipoprotein (oxLDL) in apoE-/-, the effect of oxLDL on
      lung endothelial permeability and inflammation was assessed. RESULTS: In both in
      vivo models, apoE-/- mice demonstrated greater increases in lung lavage protein
      levels, neutrophil counts, and cytokine expression (p < 0.05) compared to WT
      mice. Experiments utilizing the IPML setup demonstrated no differences in
      intrinsic lung responses to injury between apoE-/- and WT mice, suggesting the
      presence of a circulating factor as being responsible for the in vivo
      observations. Finally, the exposure of lung endothelial cells to oxLDL resulted
      in increased monolayer permeability and IL-6 release compared to native
      (nonoxidized) LDL. CONCLUSIONS: Our findings demonstrate a susceptibility of apoE
      /- animals to ALI that may occur, in part, due to elevated levels of oxLDL.

PMID- 24662318
TI  - Characterization and prevalence of severe primary IGF1 deficiency in a large
      cohort of French children with short stature.
AB  - OBJECTIVE: The prevalence of severe primary IGF1 deficiency (IGFD) is unclear.
      IGFD must be identified promptly as treatment with recombinant human IGF1
      (rhIGF1) is now available. Our objective was to characterize and assess the
      prevalence of severe primary IGFD in a large cohort of patients evaluated for
      short stature at a pediatric endocrinology unit in France. DESIGN: Observational
      study in a prospective cohort. METHODS: Consecutive patients referred to our unit
      between 2004 and 2009 for suspected slow statural growth were included. Patients
      were classified into eight etiological categories. IGFD was defined by height <=
      3 SDS, serum IGF1 levels <2.5th percentile, GH sufficiency, and absence of causes
      of secondary IGFD. RESULTS: Out of 2546 patients included, 337 (13.5%) were born
      small for gestational age and 424 (16.9%) had idiopathic short stature. In these
      two categories, we identified 30 patients who met our criterion for IGFD
      (30/2546, 1.2%). In these 30 patients, we assessed the response to IGF1
      generation test, time course of IGF1 levels, and efficiency of GH replacement
      therapy. The results indicated that only four of the 30 children were definite or
      possible candidates for rhIGF1 replacement therapy. CONCLUSION: The prevalence of
      severe primary IGFD defined using the standard criterion for rhIGF1 treatment was
      1.2%, and only 0.2% of patients were eligible for rhIGF1 therapy.

PMID- 24662319
TI  - Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth
      defects: time windows of relative safety and high risk?
AB  - BACKGROUND: Antithyroid drugs (ATDs) may have teratogenic effects when used in
      early pregnancy. OBJECTIVE: To review the association between the time period of
      ATD exposure in early pregnancy and the development of birth defects. METHODS: We
      identified publications on birth defects after early pregnancy exposure to the
      ATDs methimazole (MMI; and its prodrug carbimazole (CMZ)) and propylthiouracil
      (PTU). Cases of birth defects after ATD treatment had been initiated or
      terminated within the first 10 weeks of pregnancy were identified and studied in
      detail. RESULTS: A total of 92 publications were read in detail. Two recent large
      controlled studies showed ATD-associated birth defects in 2-3% of exposed
      children, and MMI/CMZ-associated defects were often severe. Out of the total
      number of publications, 17 included cases of birth defects with early pregnancy
      stop/start of ATD treatment, and these cases suggested that the high risk was
      confined to gestational weeks 6-10, which is the major period of organogenesis.
      Thus, the cases reported suggest that the risk of birth defects could be
      minimized if pregnant women terminate ATD intake before gestational week 6.
      CONCLUSION: Both MMI and PTU use in early pregnancy may lead to birth defects in
      2-3% of the exposed children. MMI-associated defects are often severe. Proposals
      are given on how to minimize the risk of birth defects in fertile women treated
      for hyperthyroidism with ATDs.

PMID- 24662320
TI  - Tapentadol inhibits calcitonin gene-related peptide release from rat brainstem in
      vitro.
AB  - We have previously developed an in vitro model of rat brainstem explants. The
      latter release sizable amounts of calcitonin gene-related peptide (CGRP); basal
      release can be stimulated by such secretagogues as high KCl concentrations,
      veratridine or capsaicine. In this paradigm we investigated the activity of the
      analgesic agent tapentadol; the effects of tapentadol were compared to those of a
      classical opioid receptor agonist, morphine, and the selective noradrenaline
      reuptake inhibitor reboxetine. Morphine inhibited basal CGRP release, with
      statistical significance from 1 nM onward and maximal (-44%) inhibition at 100
      MUM. Morphine also inhibited K(+)-stimulated peptide release, with a significant
      effect from 1 MUM and maximal (-39%) decrease at 100 MUM, but failed to inhibit
      release stimulated by 10 MUM capsaicin. At variance, reboxetine had no effect on
      baseline CGRP outflow, but was able to inhibit both K(+)-stimulated [significant
      inhibition from 1 MUM onward and maximal (-37%) decrease at 100 MUM], and
      capsaicin-stimulated release [significant effect from 1 MUM and maximal (-31%)
      decrease at 100 MUM]. Likewise, tapentadol had no effect on baseline CGRP release
      up to 100 MUM, but decreased secretion stimulated by 56 mM KCl or capsaicin, with
      significant effects from 0.1 and 1 MUM respectively; maximal inhibition over 56
      mM KCl and capsaicin stimuli was -29% and -31%, respectively. Naloxone
      antagonized the effect of morphine, but not those of reboxetine and tapentadol,
      on K(+)-stimulated CGRP secretion. In conclusion the present study provides
      consistent pharmacological evidence that tapentadol acts as a noradrenaline
      reuptake inhibitor agent in this experimental model.

PMID- 24662321
TI  - Complete alleviation of treatment refractory primary SUNCT syndrome with
      clomiphene citrate (a medicinal deep brain hypothalamic modulator).
AB  - OBJECTIVE: To report the first ever case of primary short-lasting unilateral
      neuralgiform headache attacks (SUNCT) syndrome completely responsive to
      clomiphene citrate. METHODS: Case report. RESULTS: SUNCT is a primary headache
      disorder marked by frequent attacks of one-sided headache with cranial autonomic
      associated symptoms. When SUNCT is deemed medicinally treatment refractory, it
      can cause tremendous patient-related disability. Surgical treatment options are
      available including hypothalamic deep brain stimulation, occipital nerve
      stimulator placement or arterial decompression surgery, but these procedures
      carry significant morbidity. A patient presented with a 10 month complaint of
      multiple, daily short-lasting, right-sided headaches each lasting from 60 to 120
      seconds in duration and occurring from 100 to 200 times per day. The head pain
      was associated with ipsilateral eyelid ptosis and conjunctival injection. The
      patient was diagnosed with SUNCT but was unresponsive to multiple recognized
      medicinal treatments. He had complete alleviation of his attacks with clomiphene
      citrate, a synthetic, non-steroidal, ovulatory stimulant that directly binds to
      hypothalamic estrogen receptors. The clomiphene was tolerated without any adverse
      events. A putative mechanism of action for clomiphene in the prevention of SUNCT
      will be presented. CONCLUSION: Clomiphene citrate is a unique treatment for SUNCT
      and appears to be very safe and effective.

PMID- 24662322
TI  - Cardiovascular and hemodynamic parameters in women following prolonged CGRP
      inhibition using LBR-101, a monoclonal antibody against CGRP.
AB  - BACKGROUND: The vascular effects of acute calcitonin gene-related peptide (CGRP)
      inhibition are well described, but the effects of sustained inhibition warrant
      further exploration in humans. OBJECTIVES: The objective of this article is to
      assess the effects of sustained CGRP inhibition on blood pressure, heart rate,
      and ECGs in healthy women >= 40 years of age. METHODS: In this double-blind,
      placebo-controlled study, 31 women (mean age = 56) were randomized to receive
      placebo or an anti-CGRP monoclonal antibody at doses up to 2000 mg. Participants
      were confined for seven days and followed for 168 days. Cardiac telemetry was
      conducted for eight hours after infusion completion. Hemodynamic assessments and
      ECGs were conducted six times during Day 1 and periodically for three months.
      RESULTS: No clinically relevant changes in systolic or diastolic blood pressure,
      heart rate, or ECG parameters (RR, PR, QRS, or QTcF) were observed when comparing
      baseline vs. post-dose time-points or in-between groups. No significant changes
      were seen for adjusted QTcF (baseline subtracted and placebo and baseline
      subtracted). No significant differences or relevant abnormalities were seen when
      comparing parameters obtained at Tmax vs. any other time-point. CONCLUSION:
      Sustained CGRP inhibition was not associated with hemodynamic or ECG changes in a
      population at an increased age risk for cardiovascular events.

PMID- 24662323
TI  - Central vestibular system modulation in vestibular migraine.
AB  - BACKGROUND: Vestibular migraine affects 1% of the general population, and 30%-50%
      of all migraine patients describe occasionally associated vertigo or dizziness.
      We aimed to identify brain regions altered in vestibular migraine in order to
      evaluate the connection between migraine and the vestibular system. METHODS:
      Seventeen patients with definite vestibular migraine were compared to 17 controls
      using magnetic resonance imaging-based voxel-based morphometry. RESULTS: We found
      grey matter (GM) volume reduction in the superior, inferior and middle (MT/V5)
      temporal gyrus as well as in the mid. cingulate, dorsolateral prefontal, insula,
      parietal and occipital cortex. A negative correlation of disease duration and GM
      volume was observed in areas associated with pain and vestibular processing.
      Moreover, there was a negative correlation between headache severity and
      prefrontal cortex volume. CONCLUSION: Alterations identified in vestibular
      migraine resemble those previously described for migraine, but also extend to
      areas involved in multisensory vestibular control and central vestibular
      compensation possibly representing the pathoanatomic connection between migraine
      and the vestibular system.

PMID- 24662324
TI  - Evidence for the presence of sex steroid hormones in Zhikong scallop, Chlamys
      farreri.
AB  - To obtain evidence of the presence of sex steroid hormones in mollusks, hormone
      variation in the gonads of the Zhikong scallop Chlamys farreri was analyzed using
      UPLC-MS/MS. These were found, as expected, with concentrations of estrone (E1),
      17beta-estradiol (E2), and testosterone (T) in the testes ranging from not
      detected (ND) to 0.07 +/- 0.10, ND to 3.10 +/- 2.00, and ND to 2.67 +/- 1.55 ng/g
      wet weight, respectively. In the ovaries, these hormones ranged from ND to 2.45
      +/- 1.22, ND to 27.90 +/- 4.23, and ND to 2.38 +/- 1.56 ng/g ww, respectively.
      The levels of T in males and E2 in females followed a trend similar to the
      gonadal-somatic index over the course of the reproductive period. In addition,
      the gene expression of vitellogenin and calmodulin-2 showed similar patterns to T
      and E2, while the estrogen receptors and calmodulin-1 did not. These results
      indicate that sex steroids are present in the scallop and that they may regulate
      endocrine functions during the reproductive process.

PMID- 24662326
TI  - Detection of graphene domains and defects using liquid crystals.
AB  - The direct observation of the domain size and defect distribution in a graphene
      film is important for the development of electronic applications involving
      graphene. Here we report a promising method for observing graphene domains grown
      by chemical vapour deposition. The unavoidable development of crack or pinhole
      defects during the growth and transfer processes is visualized using a liquid
      crystal layer. Liquid crystal molecules align anisotropically with respect to the
      graphene domains and exhibit distinct birefringence properties that can be used
      to image the graphene domains. This approach is useful for visualizing the crack
      distributions and their generation process in graphene films under external
      strain. This type of simple observation method provides an effective route to
      evaluating the quality and reliability of graphene sheets for use in various
      electronic devices. 

PMID- 24662325
TI  - The N-terminal domain of the androgen receptor drives its nuclear localization in
      castration-resistant prostate cancer cells.
AB  - Androgen-independent nuclear localization is required for androgen receptor (AR)
      transactivation in castration-resistant prostate cancer (CRPC) and should be a
      key step leading to castration resistance. However, mechanism(s) leading to
      androgen-independent AR nuclear localization are poorly understood. Since the N
      terminal domain (NTD) of AR plays a role in transactivation under androgen
      depleted conditions, we investigated the role of the NTD in AR nuclear
      localization in CRPC. Deletion mutagenesis was used to identify amino acid
      sequences in the NTD essential for its androgen-independent nuclear localization
      in C4-2, a widely used CRPC cell line. Deletion mutants of AR tagged with green
      fluorescent protein (GFP) at the 5'-end were generated and their signal
      distribution was investigated in C4-2 cells by fluorescent microscopy. Our
      results showed that the region of a.a. 294-556 was required for androgen
      independent AR nuclear localization whereas a.a. 1-293 mediates Hsp90 regulation
      of AR nuclear localization in CRPC cells. Although the region of a.a. 294-556
      does not contain a nuclear import signal, it was able to enhance DHT-induced
      import of the ligand binding domain (LBD). Also, transactivation of the NTD could
      be uncoupled from its modulation of AR nuclear localization in C4-2 cells. These
      observations suggest an important role of the NTD in AR intracellular trafficking
      and androgen-independent AR nuclear localization in CRPC cells. 

PMID- 24662327
TI  - Id-1, a protein repressed by miR-29b, facilitates the TGFbeta1-induced epithelial
      mesenchymal transition in human ovarian cancer cells.
AB  - BACKGROUND: Transforming growth factor beta 1 (TGFbeta1) can induce epithelial
      mesenchymal transition (EMT) in various human cancers, but the complex mechanisms
      underlying this have not been fully elucidated. Inhibitor of DNA binding 1 (Id-1)
      has been identified as a novel marker of ovarian cancer progression. This study
      aims to investigate the role of Id-1 in TGFbeta1-induced EMT in human ovarian
      cancer cells. METHODS: Ovarian cancer cells expressing or not expressing Id-1
      were incubated with TGFbeta1. Changes in the EMT markers E-cadherin, vimentin, N
      cadherin, Id-1, and miR-29b were detected using western blotting and qPCR
      analyses. Wound healing, transwell migration, and invasion assays were performed
      in cells where Id-1 was either knocked down or overexpressed. The effects of
      transfecting miR-29b mimics and inhibitors on Id-1 mRNA and protein expression
      were assessed. The interaction between miR-29b and Id-1 was confirmed using a
      luciferase reporter assay. RESULTS: Id-1 expression was increased and miR-29b
      expression was repressed in TGFbeta1-responsive ovarian cancer cells. Id-1
      overexpression increases and Id-1 knockdown decreases cell migration and invasion
      capacities. Id-1 silencing leads to a partial blocking of TGFbeta1-induced EMT.
      miR-29b negatively regulates Id-1 expression. Direct binding of miR-29b to the
      3'UTR region of Id-1 was confirmed using a luciferase reporter assay. CONCLUSION:
      Id-1, a protein repressed by miR-29b, facilitates TGFbeta1-induced EMT in human
      ovarian cancer cells and represents a promising therapeutic target for treating
      ovarian cancer.

PMID- 24662328
TI  - Successful nonsurgical transfer of bovine elongating conceptuses and its
      application to sexing.
AB  - The objectives of the present study were to establish a nonsurgical transfer
      method for elongating bovine conceptuses and to combine this method with biopsy
      and sexing. Bovine conceptuses were recovered from donor cows on days 13-14 of
      the estrus cycle. In experiment 1, day 13 conceptuses were transferred to
      recipient cows using a standard day 7 embryo transfer (ET) method. The pregnancy
      rate of day 13 conceptus transfer (CT) is comparable to that of day 7 ET. In
      experiment 2, day 14 conceptuses were transferred using modified methods (balloon
      catheters or ET guns with modified sheaths). Using the standard ET method, no
      pregnancies were obtained; however, when balloon catheters or ET guns with
      modified sheaths were used, the pregnancy rates after CT were 48.0% and 44.8%,
      respectively. In experiment 3, day 14 conceptuses were biopsied without a
      micromanipulator, sexed using the loop-mediated isothermal amplification method
      and transferred to recipient cows. The pregnancy rate of biopsied conceptuses was
      46.2% and did not differ significantly from that of unbiopsied conceptuses.
      Moreover, all pregnant cows transferred conceptuses following biopsy and sexing
      delivered calves with the expected sexes. These results suggested that the
      nonsurgical bovine CT method was comparable to day 7 ET and that this technique
      enables biopsy and sexing without expensive equipment such as a micromanipulator
      or specialized skills. 

PMID- 24662329
TI  - Population genetic analysis of 12 X-STRs in a Somali population sample.

PMID- 24662330
TI  - Developing a fellowship curriculum in women's gastrointestinal health.

PMID- 24662331
TI  - Insulin-producing intestinal K cells protect nonobese diabetic mice from
      autoimmune diabetes.
AB  - BACKGROUND & AIMS: Type 1 diabetes is caused by an aberrant response against
      pancreatic beta cells. Intestinal K cells are glucose-responsive endocrine cells
      that might be engineered to secrete insulin. We generated diabetes-prone non
      obese diabetic (NOD) mice that express insulin, via a transgene, in K cells. We
      assessed the effects on immunogenicity and diabetes development. METHODS:
      Diabetes incidence and glucose homeostasis were assessed in NOD mice that
      expressed mouse preproinsulin II from a transgene in K cells and nontransgenic
      NOD mice (controls); pancreas and duodenum tissues were collected and analyzed by
      histology. We evaluated T cell responses to insulin, levels of circulating
      autoantibodies against insulin, and the percentage of circulating antigen
      specific T cells. Inflammation of mesenteric and pancreatic lymph node cells was
      also evaluated. RESULTS: The transgenic mice tended to have lower blood levels of
      glucose than control mice, associated with increased plasma levels of
      immunoreactive insulin and proinsulin. Fewer transgenic mice developed diabetes
      than controls. In analyses of pancreas and intestine tissues from the transgenic
      mice, insulin-producing K cells were not affected by the immune response and the
      mice had reduced destruction of endogenous beta cells. Fewer transgenic mice were
      positive for insulin autoantibodies compared with controls. Cells isolated from
      mesenteric lymph nodes of the transgenic mice had significantly lower rates of
      proliferation and T cells from transgenic mice tended to secrete lower levels of
      inflammatory cytokines than from controls. At 15 weeks, transgenic mice had fewer
      peripheral CD8(+) T cells specific for NRP-V7 than control mice. CONCLUSIONS: NOD
      mice with intestinal K cells engineered to express insulin have reduced blood
      levels of glucose, are less likely to develop diabetes, and have reduced immunity
      against pancreatic beta cells compared with control NOD mice. This approach might
      be developed to treat patients with type 1 diabetes.

PMID- 24662332
TI  - Human corneal epithelial cells produce antimicrobial peptides LL-37 and beta
      defensins in response to heat-killed Candida albicans.
AB  - AIMS: To explore the innate response of human corneal epithelial cells (HCECs)
      exposed to fungus by producing antimicrobial peptides LL-37 and beta-defensins.
      METHODS: Primary HCECs were treated with heat-killed Candida albicans (HKCA) at
      different doses (10(3)-10(6) cells/ml) for 2-48 h. The cells were subjected to
      total RNA extraction, reverse transcription and quantitative real-time PCR for
      mRNA expression. Cells treated for 48 h were used for immunofluorescent staining
      and ELISA. RESULTS: Human LL-37 and beta-defensins (hBDs) 1-4 were detected in
      normal HCECs. The mRNA expression of LL-37, hBD2, and hBD3 was dose-dependently
      induced by HKCA with their peak levels at 4 h. HKCA (10(6) cells/ml) stimulated
      the mRNA of LL-37, hBD2, and hBD3 4.33 +/- 1.81, 3.75 +/- 1.31, and 4.91 +/- 1.09
      fold, respectively, in HCECs. The stimulated production of LL-37, hBD2, and hBD3
      by HKCA was confirmed at protein levels by immunofluorescent staining and ELISA.
      The protein production of LL-37, hBD2, and hBD3 significantly increased to 109.1
      +/- 18.2 pg/ml, 4.33 +/- 1.67 ng/ml, and 296.9 +/- 81.8 pg/ml, respectively, in
      culture medium of HCECs exposed to HKCA (10(6) cells/ml) compared to untreated
      HCECs. CONCLUSIONS: HCECs produce antimicrobial peptides, LL-37, hBD2 and hBD3,
      in response to stimulation of HKCA, which suggests a novel innate immune
      mechanism of the ocular surface in defense against fungal invasion.

PMID- 24662334
TI  - Iterative image reconstruction techniques: cardiothoracic computed tomography
      applications.
AB  - Iterative image reconstruction algorithms provide significant improvements over
      traditional filtered back projection in computed tomography (CT). Clinically
      available through recent advances in modern CT technology, iterative
      reconstruction enhances image quality through cyclical image calculation,
      suppressing image noise and artifacts, particularly blooming artifacts. The
      advantages of iterative reconstruction are apparent in traditionally challenging
      cases-for example, in obese patients, those with significant artery
      calcification, or those with coronary artery stents. In addition, as clinical use
      of CT has grown, so have concerns over ionizing radiation associated with CT
      examinations. Through noise reduction, iterative reconstruction has been shown to
      permit radiation dose reduction while preserving diagnostic image quality. This
      approach is becoming increasingly attractive as the routine use of CT for
      pediatric and repeated follow-up evaluation grows ever more common.
      Cardiovascular CT in particular, with its focus on detailed structural and
      functional analyses, stands to benefit greatly from the promising iterative
      solutions that are readily available. 

PMID- 24662333
TI  - A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis
      of pancreatic cancer.
AB  - BACKGROUND & AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)
      in combination with cytopathology is the optimal method for diagnosis and staging
      of pancreatic ductal adenocarcinoma (PDAC) and other pancreatic lesions. Its
      clinical utility, however, can be limited by high rates of indeterminate or false
      negative results. We aimed to develop and validate a microRNA (miRNA)-based test
      to improve preoperative detection of PDAC. METHODS: Levels of miRNAs were
      analyzed in a centralized clinical laboratory by relative quantitative polymerase
      chain reaction in 95 formalin-fixed paraffin-embedded specimens and 228 samples
      collected by EUS-FNA during routine evaluations of patients with solid pancreatic
      masses at 4 institutions in the United States, 1 in Canada, and 1 in Poland.
      RESULTS: We developed a 5-miRNA expression classifier, consisting of MIR24,
      MIR130B, MIR135B, MIR148A, and MIR196, that could identify PDAC in well
      characterized, formalin-fixed, paraffin-embedded specimens. Detection of PDAC in
      EUS-FNA samples increased from 78.8% by cytology analysis alone (95% confidence
      interval, 72.2%-84.5%) to 90.8% when combined with miRNA analysis (95% confidence
      interval, 85.6%-94.5%). The miRNA classifier correctly identified 22 additional
      true PDAC cases among 39 samples initially classified as benign, indeterminate,
      or nondiagnostic by cytology. Cytology and miRNA test results each were
      associated significantly with PDAC (P < .001), with positive predictive values
      greater than 99% (95% confidence interval, 96%-100%). CONCLUSIONS: We developed
      and validated a 5-miRNA classifier that can accurately predict which preoperative
      pancreatic EUS-FNA specimens contain PDAC. This test might aid in the diagnosis
      of pancreatic cancer by reducing the number of FNAs without a definitive
      adenocarcinoma diagnosis, thereby reducing the number of repeat EUS-FNA
      procedures.

PMID- 24662335
TI  - Computed tomography evaluation of cardiac structure and function.
AB  - Computed tomography is a noninvasive imaging modality that can be used for the
      evaluation of cardiac structure and function. This review provides an overview of
      established and emerging applications of cardiac computed tomography, including
      evaluation of left and right ventricular function, ventricular morphology, native
      and prosthetic valves, and pulmonary and coronary vein anatomy. 

PMID- 24662336
TI  - Magnetic resonance of coronary arteries: assessment of luminal narrowing and
      blood flow in the coronary arteries.
AB  - The assessment of luminal narrowing and altered blood flow in the coronary artery
      is challenging because of the small size of the vessel and the complex motion
      caused by cardiac contraction and respiration. Free-breathing, whole-heart
      coronary magnetic resonance angiography (MRA) has been introduced as a method
      that can provide visualization of all 3 major coronary arteries within a single 3
      dimensional acquisition, either by using 1.5 T steady-state free precession or 3
      T gradient-echo sequences. Recent studies have indicated that coronary MRA has
      sufficient diagnostic accuracy for excluding coronary artery disease (CAD) in
      patients with suspected CAD. Furthermore, coronary MRA can provide risk
      stratification for future cardiac events. In addition to the morphologic
      assessment of the coronary artery, phase-contrast cine MR imaging has unique
      advantages because it allows for measurement of blood flow and flow reserve in
      the coronary arteries. Comprehensive assessment of the morphology and blood flow
      in the coronary artery has a great potential in noninvasive detection of
      physiologically significant CAD that requires revascularization. The aim of this
      review is to provide an update on current technical improvements in coronary MRA
      and MR flow measurement of coronary arteries. 

PMID- 24662337
TI  - [Basilar type migraine: clinical features, differential diagnosis].
AB  - The work is devoted to the description of neurological, vestibulometric and
      audiologic data obtained in the examination of 11 patients with basilar type
      migraine. The features of the disease (neck injuries before the disease,
      prolonged aura, protracted attacks, similarity with the clinical picture of
      stroke, occipital pain, cervical root syndrome, muscle-tonus phenomena and
      others) are described. A role of cervical pathology and labyrinthine hydrops in
      the disease pathogenesis as well as difficulties of differential diagnosis with
      Meniere's disease and Barre-Lieou syndrome are discussed. 

PMID- 24662338
TI  - [Cognitive functions and personality traits in patients with brain tumors: the
      role of lesion localization].
AB  - Personality traits and cognitive functions were studied depending on a tumor
      localization in the brain in 21 neurosurgical patients and the results were
      compared with a control group. In patients with brain damage, mostly affected
      were personality traits associated with emotion regulation and social interaction
      (neuroticism, psychoticism and social conformity). Increases in psychoticism and
      decreases in neuroticism were more expressed in patients with a left-hemisphere
      localization of tumors. The tumor-induced decrease in cognitive abilities was
      more presented in performing figurative tasks and less in verbal ones. Verbal
      functions were more decreased in the group with frontal localization of tumor
      compared to that with parietal localization. 

PMID- 24662339
TI  - [Factors of intercellular interaction in acute ischemic stroke].
AB  - 29 patients with acute carotid and vertebrobasilar stroke caused by combination
      of atherosclerosis and arterial hypertension were examined, of them 8 patients
      were diagnosed as having type II diabetes mellitus. Clinical manifestations and
      blood serum levels of adhesion molecules (AM) in dynamics (48 h and 21st-day) of
      acute ischemic stroke (IS) were estimated. Soluble AM levels were significantly
      elevated in patients with acute IS compared with controls. The highest levels of
      AM were found in IS predominantly on the 1-2 days. Levels of AM were
      significantly higher in patients with severe stroke. Diabetes mellitus promotes
      the hyperproduction of adhesion molecules. Given the role of AM in endothelian
      disfunction genesis and tissue damage associated with IS, they could constitute a
      therapeutic target for prevention of the progression neurological deficit. 

PMID- 24662340
TI  - [Cognitive functions in patients with primary torsion dystonia treated with
      pallidal deep brain stimulation].
AB  - Forty-three patients with primary dystonia underwent neuropsychological
      assessment according to the method of A.R. Luria. Twenty-three patients with
      generalized dystonia and 20 with local forms (cervical and craniocervical) were
      included in the study. All patients were evaluated before pallidal deep brain
      stimulation (DBS GPi), 32 patients were examined 3-6 days after surgery, and 26
      patients - during the first two years of the postoperative follow-up. The
      evaluation before surgery revealed cognitive impairment in 41 patients. The most
      common were mnemonic impairment, inertness and preservation in different tests,
      and spatial function decline. Thus, patients with local forms more frequently had
      troubles with performance memory tests, whereas spatial function disorders were
      more common in patients with generalized forms. The deterioration of cognitive
      functions was observed in 28 patients in the early postoperative period.
      Moreover, the group of patients with local forms had poorer results. The
      neuropsychological evaluation after 3-6 months of the postoperative follow-up
      showed the restoration of cognitive functions to the preoperative level.
      Neuropsychological syndrome observed in patients with dystonia was generally
      similar to that found in patients with lesions of the frontal lobe, the caudate
      nucleus, and the cerebellum.

PMID- 24662342
TI  - [Results of the spectral analysis of electroencephalograms of patients with focal
      epileptic seizures in the interictal period].
AB  - A comparative spectral analysis of electroencephalograms in patients with focal
      and generalized epileptic seizures in the interictal period revealed some
      specific characteristics of these paroxysms. Slowing of dominating alpha-rhythm
      was seen in case of the localization of epileptiform activity in frontal-central
      temporal and occipital-parietal areas with the further spreading of epileptiform
      activity to the temporal area. Asymmetry of dominating alpha-rhythm in the right
      hemisphere was found in patients with focal paroxysms, asymmetry of theta-rhythm
      in all patients, of beta-2 rhythm in patients over 45 years old and of delta-2
      rhythm in female patients. 

PMID- 24662341
TI  - [Influence of cytoflavin on symptoms of asthenia, emotional disorders and
      autonomic regulation in patients with organic asthenic disorder].
AB  - The present observational study addressed effects of cytoflavine on symptoms of
      asthenia and emotional and autonomic regulation in patients with organic
      emotional-labile (asthenic) disorder (F06.6). Fifty one females and 49 males
      (mean age 36.8+/-11.0 years) were included into the study during their in-patient
      treatment in Moscow Research and Clinical Center for Neuropsychiatry of the
      Healthcare Department. All patients received standard antidepressant and vascular
      therapy, were consulted by psychologists or psychotherapists, visited
      physiotherapeutic procedures, massage and medical physical training. In addition,
      50 patients received cytoflavin two tablets twice per day. At the psychiatric re
      assessment before discharge both cytoflavin and control groups showed similar
      significant reduction of asthenia symptoms. At the same time, patients with
      cognitive deficits showed significantly larger improvement of cognitive functions
      after cytoflavin treatment in comparison with cognitively deficient patients
      after only standard therapy. Improvement of depressive symptoms was significantly
      larger in cytoflavin group in comparison with controls as well. These data are
      consistent with previous studies which showed cytoflavin to be effective as a
      treatment for patients with cognitive deficits and organic depression. 

PMID- 24662343
TI  - [Immunological monitoring of endogenous attack-like psychoses].
AB  - To analyze the possibility of using immunological parameters for the assessment
      of the activity of the process and prediction of the quality and completion of
      remission, we compared the dynamics of clinical and immunological parameters in
      76 patients with endogenous attack-like psychoses during pharmacotherapy of a
      psychotic episode. Authors confirmed evidence for the activation of innate and
      adaptive immunity in the acute stage of psychosis as well as the correlation
      between immunological parameters (leukocyte elastase (LE) activity, alpha(1)
      proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth
      factor (Aab-NGF)) and clinical symptoms assessed with the PANSS. The improvement
      of the clinical state assessed by the reduction in PANSS total score was noted in
      all patients though there were variations in the dynamics of immunological
      parameters. The increase of immunological parameters, along with the absence of
      changes at the discharge from the hospital, suggests that the remission was of
      low quality and the pathological process did not attenuate. Outpatient
      examination revealed the different dynamics of psychopathological disorders:
      stable state in 50% patients, moderate worsening of psychological state in 50%
      patients. Worsening of clinical symptoms after the discharge and in the
      outpatient stage was correlated with the elevation of the activity/level of
      immunological parameters. The changes in LE activity and Aab-NGF level precede
      the changes in mental state of patients in the following 1-2 months. These
      parameters may be used for monitoring of patients and prediction of quality and
      completion of remission. 

PMID- 24662344
TI  - [Ultrastructural changes in platelets and their relationship with serotonin
      metabolism in patients with schizophrenia treated with olanzapine].
AB  - An aim of the study was to investigate the effect of olanzapine treatment on
      platelet ultrastructure and to search for its association with serotonin
      metabolism in patients with schizophrenia. Platelets of 59 patients with chronic
      (attack-like schizophrenia) treated with olanzapine and 31 health people were
      explored. Based on the data on the platelet ultrastructure, authors studied the
      content of functionally activated vacuolated platelets (VP) and less active
      granular platelets (GP) as well of platelet serotonin (PS). VP content was higher
      in patients compared to the control group (+57%, p<0.001). After treatment for 8
      and 28 weeks with olanzapine, it decreased and reached the control level (52% and
      57%, respectively). There were significant negative correlations between % VP and
      PS before treatment (r= -0.30, p=0.02) and 8 week after treatment (r= -0.29,
      p<0.04) and a positive correlation between the decrease in % VP and increase in
      the PS levels during 8-week treatment (r=0.34, p=0.008). The association between
      increased platelet vacuolization and decreased PS content in schizophrenia was
      demonstrated for the first time. This association disappeared after treatment
      that led to the normalization of % VP and PS levels. 

PMID- 24662345
TI  - [The features of daily functioning of mentally ill patients: a sociological
      survey].
AB  - The data of a sociological survey of 1042 mentally ill patients are presented.
      The aim of the investigation was to study different aspects of daily functioning
      of patients with mental diseases. It has been shown that the negative
      consequences of mental disease are seen at every level (professional, family and
      social) of daily functioning. 

PMID- 24662346
TI  - [Nonspecific low-back pain: from symptomatic treatment to pathogenesis-based
      treatment].
AB  - OBJECTIVE: To study the efficacy and safety of artrosilene in the combination
      with piascledine in patients with low-back pain. METHODS: Sixty patients, 42
      women and 18 men (mean age 53,6+/-10,4 years) with chronic nonspecific low-back
      pain were treated with artrosilene (ketoprofen lysine salt) in the combination
      with the chondro protector piascledine (a mix of avocado and soybean oil
      extracts). RESULTS: There the persistent decrease in the intensity of pain
      syndrome and severity of vertebral syndrome and improvement of quality of life.
      CONCLUSIONS: The drugs can be recommended for treatment of nonspecific low-back
      pain.

PMID- 24662348
TI  - [Comments on a revised International Classification of Headache Disorders, 3rd
      edition (beta version, 2013)].

PMID- 24662347
TI  - [The use of agomelatine for the preventive treatment of migraine].

PMID- 24662349
TI  - [Multiple sclerosis in the Bashkortostan Republic and the Rostov region: a
      comparative epidemiologic study].
AB  - Epidemiological characteistics of multiple sclerosis (MS) in the Bashkortostan
      Republic (BR) and the Rostov region have been compared. Prevalence and incidence
      of MS were higher in BR (38.0 and 2.92 per 100 000) compared to the Rostov region
      (29.8 and 0.73 per 100 000). This finding may be explained by geographic and
      ethnic differences. The comparative analysis suggests that both environmental and
      genetic factors contribute to the etiology of MS. 

PMID- 24662350
TI  - [Clinical epidemiology of multiple sclerosis in Moscow. Slinical demo-graphic
      characteristics in population of one region of Moscow].
AB  - The changes in clinical features of multiple sclerosis (MS) are noted worldwide
      which can be explained by diagnosis improvement and DMT implementation.
      Epidemiological studies of 2008-2012 in the North-West Administrative District of
      Moscow noted the higher proportion of women among patients of MS (M:F=1:2.61),
      longer duration of the disease (mean 14.3+/-10.6 years, maximum - 53 years) and
      life expectancy of patients (44.3+/-12.7 years, the maximum age - 77 years). The
      percentage of patients with secondary progressive course of MS increased (35%).
      In addition, MS onset before 16 years old was diagnosed more often (5.66% of
      cases) and late onset MS was identified in 4.04% of the cases. Up to 45.9% of MS
      patients have moderate and expressed disability (group 1 and 2 disability). 

PMID- 24662351
TI  - [Cancer diseases in patients with multiple sclerosis in the Bashkortostan
      Republic].
AB  - A database on patients with multiple sclerosis (MS) of the Republican center of
      multiple sclerosis (Ufa city) is analyzed. The database includes 1436 patients.
      For the period 2005-2012, 4 female patients with cancer, including 2 patients
      with thyroid gland cancer, 1 patient with rectum tumor and 1 patient with breast
      cancer, were identified. Clinical features of MS in these cases were studied. In
      two patients, cancer developed during the treatment with Beta-interferon-1b. A
      possible association of cancer with MS and multiple sclerosis disease modifying
      drugs is discussed. 

PMID- 24662352
TI  - [An analysis of the epidemiological situation on multiple sclerosis in the
      Krasnodar region].
AB  - The data of a clinical-epidemiological study of multiple sclerosis (MS) in the
      Krasnodar region are presented. The index of MS prevalence was estimated as 18.95
      per 100.000 people. That allows to consider the region as an area with mid-level
      MS risk. The disease incidence was 2.18 per 100.000 people. The prevalence and
      incidence were the highest in the Russian population, aged 35-39 years. 

PMID- 24662353
TI  - [A chronic fatigue syndrome and blood platelet serotonin levels in patients with
      multiple sclerosis].
AB  - Sixty patients with multiple sclerosis and 12 healthy controls were examined. The
      fatigue was measured by the Fatigue Severity Scale (FSS). Concentration of
      platelet serotonin was analyzed with immunoassay techniques ("Serotonin ELISA").
      The results of the study have shown the primary role of fatigue in multiple
      sclerosis, with the prevalence of this syndrome reached 57.6%. The patients with
      multiple sclerosis had low concentration of platelet serotonin that was
      correlated with clinical features of the disease. 

PMID- 24662354
TI  - [Epstein-Barr virus in the pathogenesis of multiple sclerosis (a review)].
AB  - Multiple sclerosis is now regarded as a disease, which is based on genetic
      predisposition. Trigger mechanism are various exogenous factors. The Epstein-Barr
      virus is thought to be a trigger. This report provides information about possible
      mechanisms of the influence of the Epstein-Barr virus on the development of
      multiple sclerosis. 

PMID- 24662355
TI  - [von Willebrand factor and adhesion molecules in patients with multiple
      sclerosis].
AB  - Based on a role of certain adhesion molecules and vascular endothelial damage in
      multiple sclerosis (MS), we explored C-reactive protein, von Willebrand factor,
      matrix metalloproteinase-9, sICAM-1, sPECAM-1, E-selectin and P-selectin in the
      blood of patients. One group of the patients received pathogenic therapy. There
      was the increase in the level of the von Willebrand factor in patients who did
      not receive the therapy. The levels MMP-9 and sE-selectin were correlated with
      the high activity of the disease. The authors suggest the presence of the
      endothelial dysfunction in some patients. MMP9 and sE-selectin may be considered
      as potential markers of the activity of multiple sclerosis. 

PMID- 24662356
TI  - [Light sensitivity of the visual system in patients with demyelinating optic
      neuropathy in acute retrobulbar neuritis].
AB  - Based on the data analysis of contrast-color sensitivity, contrast - frequency
      sensitivity and dynamic visual acuity, the quantitative estimation of light
      sensitivity of ill and healthy eyes of patients with demyelinating optic
      neuropathy in acute retrobulbar neuritis has been carried out. The differences
      between these functional parameters of light sensitivity of the visual system are
      used for discussion of the pathogenesis of demyelinating optic neuropathy and
      possibility of its early diagnosis. 

PMID- 24662357
TI  - [Spinal segmental myoclonus in multiple sclerosis (case report)].
AB  - Multiple sclerosis (MS) is a disease with multicentric lesions of central nervous
      system. These numerous lesions can cause a lot of different symptoms. Sometimes
      these signs are atypical and make difficulties for MS diagnosing. Hyperkinesis is
      extremely rare manifestation of MS especially if it concerns spinal myoclonus.
      Spinal myoclonic jerks can be caused by various focal damages of neuraxis
      including demyelination lesions. This report describes the case of spinal
      segmental myoclonus as an unusual manifestation of MS. The patient was diagnosed
      definite MS according to the McDonald criteria (2010). The nature of movement
      disorders was defined by careful neurologic and neurophysiologic examination.
      These movement disorders were reliably caused by demyelinating type lesions in
      the cervical cord. 

PMID- 24662358
TI  - [Posture disorders in patients with multiple sclerosis].
AB  - Impairment of stability in the vertical posture is one of the most common or,
      sometimes, a key symptom in patients with multiple sclerosis (MS). Reduction of
      postural control is often correlated with the severity of neurological deficit
      and is thought to be a leading factor that impacts on social and working
      activities of the patient with MS. We studied disturbances of postural control
      depending on the lesion of a functional system and evaluated the involvement of a
      corresponding system in the functions of postural control in 61 patients with
      confirmed MS. Patients were stratified into five groups according to lesion
      location: visual, motor, sensory, cerebellar or spine stem systems. The maximal
      impairment of static postural control corresponded to the maximal lesion of the
      sensory system. Compensatory mechanisms of the activation of central and
      neuromuscular. 

PMID- 24662359
TI  - [Oral disease modifying therapy of multiple sclerosis: the current view].
AB  - The review includes data on experimental and clinical studies of new oral methods
      of multiple sclerosis (MS) disease modifying therapy (DMT). The mechanisms of
      action, results of clinical trials of stages II and III with the data on their
      clinical and MRI-efficacy, tolerability and safety of fingolimod,
      dimethylfumarate (BG-12), teriflunomide and laquinimod are included. The risk
      management plans for possible side-effects of every product and the peculiarities
      of their use in individually selected MS treatment are discussed. 

PMID- 24662360
TI  - [The activation of the type I interferon signaling pathway in multiple sclerosis
      patients treated with russian analogue of Beta-interferon-1b: transcriptome
      profiling data].
AB  - Implementation of the analogues of Beta-interferon (Beta-IFN), produced by
      recombinant strains of E. coli (Beta-IFN-1b), for internal use in the Russian
      Federation for the treatment of multiple sclerosis (MS), implies a verification
      of their action at the transcriptome level in order to confirm the activation of
      the main signaling pathways involved in IFNb mechanism of action. In this work,
      the analysis is carried out for Infibeta (Generium, Russia). Using genome-wide
      transcriptional profiling with ILLUMINA HT-12 microarray, the differentially
      expressed genes in peripheral blood mononuclear cells of MS patients upon
      administration of Infibeta were studied. Comparison of gene expression levels in
      treatment-naive MS patients prior to first Beta-IFN administration and 10 hours
      after it, identified 490 genes with significantly changed expression level, where
      191 genes were up-regulated and 299 genes were down-regulated. Among the involved
      genes are those coding the components of the inflammatory system, innate and
      adaptive immunity, apoptosis, signal transduction, transcription, translation,
      degradation. Using gene set analysis, we confirmed the involvement of type I
      interferon signaling pathway genes and interferon-inducible genes in a patient's
      individual response to drug. Thus, the transcriptome profiling analysis allows
      concluding that the mechanism of action of Infibeta immunomodulatory drug is
      equal to that described for the original Beta-IFN drugs. 

PMID- 24662361
TI  - [Unified assessment of adverse events of multiple sclerosis disease modifying
      drugs].
AB  - One of the important components of effective treatment of multiple sclerosis is
      adherence to therapy and long-term patient compliance, as well as timely
      detection and correction of adverse events. Using disease modifying drugs (DMD)
      in general medical practice is very different from that in clinical trials, in
      particular, there is no uniform approach to identify the adverse events of
      therapy. The authors developed a form of the Adverse events of DMD questionnaire,
      and checked its reliability and validity. 

PMID- 24662362
TI  - [Side-effects of glucocorticosteroids in multiple sclerosis: a case report of a
      patient with global amnesia].
AB  - Pulse-doses of corticosteroids are actively used in the treatment of multiple
      sclerosis relapses. Short pulse-treatment is usually well-tolerated by patients
      though side-effects may be observed. We described a rare case of transient global
      amnesia after the pulse-treatment with corticosteroids. A complex examination
      excluded other causes of amnesia. 

PMID- 24662364
TI  - Encapsulation of alcohol dehydrogenase in mannitol by spray drying.
AB  - The retention of the enzyme activity of alcohol dehydrogenase (ADH) has been
      studied in various drying processes such as spray drying. The aim of this study
      is to encapsulate ADH in mannitol, either with or without additive in order to
      limit the thermal denaturation of the enzyme during the drying process. The
      retention of ADH activity was investigated at different drying temperatures. When
      mannitol was used, the encapsulated ADH was found inactive in all the dried
      powders. This is presumably due to the quick crystallization of mannitol during
      spray drying that resulted in the impairment of enzyme protection ability in
      comparison to its amorphous form. Maltodextin (dextrose equivalent = 11) was used
      to reduce the crystallization of mannitol. The addition of maltodextrin increased
      ADH activity and drastically changed the powder X-ray diffractogram of the spray
      dried powders. 

PMID- 24662363
TI  - Phototriggerable liposomes: current research and future perspectives.
AB  - The field of cancer nanomedicine is considered a promising area for improved
      delivery of bioactive molecules including drugs, pharmaceutical agents and
      nucleic acids. Among these, drug delivery technology has made discernible
      progress in recent years and the areas that warrant further focus and
      consideration towards technological developments have also been recognized.
      Development of viable methods for on-demand spatial and temporal release of
      entrapped drugs from the nanocarriers is an arena that is likely to enhance the
      clinical suitability of drug-loaded nanocarriers. One such approach, which
      utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded
      nanoparticles, will be the discussion platform of this article. Although several
      phototriggerable nanocarriers are currently under development, I will limit this
      review to the phototriggerable liposomes that have demonstrated promise in the
      cell culture systems at least (but not the last). The topics covered in this
      review include (i) a brief summary of various phototriggerable nanocarriers; (ii)
      an overview of the application of liposomes to deliver payload of
      photosensitizers and associated technologies; (iii) the design considerations of
      photoactivable lipid molecules and the chemical considerations and mechanisms of
      phototriggering of liposomal lipids; (iv) limitations and future directions for
      in vivo, clinically viable triggered drug delivery approaches and potential novel
      photoactivation strategies will be discussed. 

PMID- 24662365
TI  - Human rabies in Iran.
AB  - BACKGROUND: Like most Asian and African countries, Iran is highly endemic for
      rabies, which is a preventable disease with the timely utilisation of post
      exposure prophylaxis (PEP). With the availability of affordable vaccination in
      Iran, there are still several rabies deaths which are assumed misdiagnosed or
      received ineffective PEP. METHODS: We reviewed the files of 16 human rabies
      deaths, consisting of two groups: 1, ineffective treatment; and 2, erroneous PEP.
      RESULTS: Most of the studied cases were male and were from rural areas. Stray
      dogs were found to be the common biting animal (68.75%). Of the patients, 10/16
      (62.5%) who had injuries on their head and/or face demonstrated shorter
      incubation periods. The incubation period was longer in a 4-year-old boy who
      sustained injuries in his abdomen and back. All the patients in group 1 received
      four doses of vaccine and administration of human rabies immune globulin (HRIG),
      and death occurred with the mean of 49 days after the bite. This mean was 27 days
      in three patients in group 2, who received vaccine without administration of
      HRIG. CONCLUSION: In a total of 1,188,579 cases of PEP given in Iran during: 2002
      2011, it is not known whether all PEPs were correctly administered by World
      Health Organization standards. Extending rabies awareness programmes and timely
      PEP education in the community in accordance with the implementation of rabies
      control measures might lead to a decrease in these unfortunate scenarios and
      heavy financial burden of vaccination required due to the prevalence of rabies.

PMID- 24662366
TI  - SEM method for direct visual tracking of nanoscale morphological changes of
      platinum based electrocatalysts on fixed locations upon electrochemical or
      thermal treatments.
AB  - A general method for tracking morphological surface changes on a nanometer scale
      with scanning electron microscopy (SEM) is introduced. We exemplify the
      usefulness of the method by showing consecutive SEM images of an identical
      location before and after the electrochemical and thermal treatments of platinum
      based nanoparticles deposited on a high surface area carbon. Observations reveal
      an insight into platinum based catalyst degradation occurring during potential
      cycling treatment. The presence of chloride clearly increases the rate of
      degradation. At these conditions the dominant degradation mechanism seems to be
      the platinum dissolution with some subsequent redeposition on the top of the
      catalyst film. By contrast, at the temperature of 60 degrees C, under
      potentiostatic conditions some carbon corrosion and particle aggregation was
      observed. Temperature treatment simulating the annealing step of the synthesis
      reveals sintering of small platinum based composite aggregates into uniform
      spherical particles. The method provides a direct proof of induced surface
      phenomena occurring on a chosen location without the usual statistical
      uncertainty in usual, random SEM observations across relatively large surface
      areas.

PMID- 24662367
TI  - Effects of various extracellular matrix proteins on the growth of HL-1
      cardiomyocytes.
AB  - We present the physical and biochemical effects of extracellular matrixes (ECMs)
      on HL-1 cardiomyocytes. ECMs play major roles in cell growth, adhesion and the
      maintenance of native cell functions. We investigated the effects of 6 different
      cell culture systems: 5 different ECM-treated surfaces (fibronectin, laminin,
      collagen I, gelatin and a gelatin/fibronectin mixture) and 1 nontreated surface.
      Surface morphology was scanned and analyzed using atomic force microscopy in
      order to investigate the physical effects of ECMs. The attachment, growth,
      viability, proliferation and phenotype of the cells were analyzed using phase
      contrast microscopy and immunocytochemistry to elucidate the biochemical effects
      of ECMs. Our study provides basic information for understanding cell-ECM
      interactions and should be utilized in future cardiac cell research and tissue
      engineering.

PMID- 24662369
TI  - Anxiety sensitivity and negative urgency: a pathway to negative reinforcement
      related smoking expectancies.
AB  - OBJECTIVES: Anxiety sensitivity--fear of anxiety symptoms--may increase
      motivation to smoke by influencing the development of cognitive expectations
      regarding smoking's negative reinforcing effects; yet, the nature and mechanisms
      of this pathway are unclear. We hypothesized that relations between anxiety
      sensitivity and negative reinforcement-related smoking expectancies would be
      mediated by negative urgency, that is, a trait tendency to act impulsively during
      negative affect. METHODS: In a cross-sectional design, we administered self
      report measures of anxiety sensitivity, negative urgency, and negative
      reinforcement-related smoking outcome and abstinence expectancies to 205 smokers
      (>=10 cigarettes/d, 34% female, M age = 44.4 years). RESULTS: Anxiety sensitivity
      was associated with stronger expectancies that smoking alleviates negative affect
      (beta = 0.30; P < 0.0001) and smoking abstinence exacerbates aversive withdrawal
      symptoms (beta = 0.24; P = 0.0004). Negative urgency partially mediated the
      relation between anxiety sensitivity and both types of negative reinforcement
      related smoking expectancies (betas >= 0.057; Ps <= 0.007). Results remained
      significant after statistically controlling for anxiety and nicotine dependence
      symptoms. CONCLUSIONS: Smokers high in anxiety sensitivity tend to display
      negative urgency, which in turn is related to greater expectations of negative
      reinforcement consequences of smoking and smoking abstinence. Treatments that
      mitigate fear of anxiety symptoms and the tendency to act impulsively in response
      to negative affect (eg, interoceptive exposure, distress tolerance skills
      training, and mindfulness training) may be particularly useful in assisting with
      smoking cessation for high-anxiety sensitivity smokers.

PMID- 24662370
TI  - Evaluation of quetiapine abuse and misuse reported to poison centers.
AB  - OBJECTIVE: There are case reports of abuse of quetiapine, but no studies address
      quetiapine abuse or misuse. Most literature on the population that abuses
      quetiapine describes an older age group with previous substance abuse history,
      many of whom are in jail. The objective of this study was to evaluate national
      poison center data on misuse/abuse of quetiapine. METHODS: A retrospective study
      of American Association of Poison Control Centers National Poison Data System
      data from 2005 to 2011 on single substance quetiapine exposures coded as
      intentional misuse or abuse and followed to known outcome was performed. Data
      were evaluated for age, toxicity, management sites, treatments, and medical
      outcomes. RESULTS: There were 3116 cases meeting inclusion criteria; reason was
      misuse in 1948 cases and abuse in 1168 cases. The median age was 23 years. Misuse
      was reported most often in adults, whereas abuse occurred most frequently in
      adolescents. The male-to-female ratio was 1.7 for abuse and 1.0 for misuse. There
      were no deaths. Moderate or major toxicity occurred in 23.7% and 27.1% of misuse
      and abuse cases, respectively. Seventy-six percent were treated in the emergency
      department and/or received medical admission. CONCLUSIONS: Misuse was more common
      than abuse, except in adolescents for whom abuse was more frequent. Although
      outcomes were generally good, significant toxicity occurred in 25% of cases and
      more than 75% of the patients were treated in the emergency department and/or
      received medical admission. The consequences of nonmedical use of quetiapine are
      serious in some patients.

PMID- 24662368
TI  - Sex and the migraine brain.
AB  - The brain responds differently to environmental and internal signals that relate
      to the stage of development of neural systems. While genetic and epigenetic
      factors contribute to a premorbid state, hormonal fluctuations in women may alter
      the set point of migraine. The cyclic surges of gonadal hormones may directly
      alter neuronal, glial and astrocyte function throughout the brain. Estrogen is
      mainly excitatory and progesterone inhibitory on brain neuronal systems. These
      changes contribute to the allostatic load of the migraine condition that most
      notably starts at puberty in girls. 

PMID- 24662371
TI  - Benzodiazepine use among young attendees of an Irish substance treatment center.
AB  - OBJECTIVE: To describe the demographic characteristics of those service users
      attending Matt Talbot Services, and their current and past substance use, and to
      explore the use of benzodiazepines among this group. METHOD: There were 198
      service users who attended a substance misuse treatment center in Cork, Ireland,
      between January 2005 and August 2011. RESULTS: Benzodiazepines had ever been used
      by 51.0%, and of these, 55.8% were regular benzodiazepine users. The mean age of
      first use was 14.9 +/- 1.4 years. Regular users of benzodiazepines were regular
      users of significantly more substances (3, interquartile range [IQR] = 2-3) when
      compared with nonregular benzodiazepine users (1, IQR = 1-2). Regular
      benzodiazepine users showed more behavioral signs (12, IQR = 10-14) than
      nonregular users (9, IQR = 7-12). Physical signs were significantly different
      between regular (8, IQR = 6-11) and nonregular (5, IQR = 3-10) users.
      CONCLUSIONS: The effects of benzodiazepine misuse affect the individual, their
      family, and society as a whole through hospitalization, substance treatment, and
      crime. Identifying regular benzodiazepine users can help reduce the burden of
      benzodiazepines.

PMID- 24662372
TI  - 60S ribosome biogenesis requires rotation of the 5S ribonucleoprotein particle.
AB  - During eukaryotic ribosome biogenesis, nascent ribosomal RNA (rRNA) forms pre
      ribosomal particles containing ribosomal proteins and assembly factors.
      Subsequently, these immature rRNAs are processed and remodelled. Little is known
      about the premature assembly states of rRNAs and their structural rearrangement
      during ribosome biogenesis. Using cryo-EM we characterize a pre-60S particle,
      where the 5S rRNA and its associated ribosomal proteins L18 and L5 (5S
      ribonucleoprotein (RNP)) are rotated by almost 180 degrees  when compared with
      the mature subunit. Consequently, neighbouring 25S rRNA helices that protrude
      from the base of the central protuberance are deformed. This altered topology is
      stabilized by nearby assembly factors (Rsa4 and Nog1), which were identified by
      fitting their three-dimensional structures into the cryo-EM density. We suggest
      that the 5S RNP performs a semicircular movement during 60S biogenesis to adopt
      its final position, fulfilling a chaperone-like function in guiding the flanking
      25S rRNA helices of the central protuberance to their final topology. 

PMID- 24662373
TI  - Liver X receptor beta delays transformation of radial glial cells into astrocytes
      during mouse cerebral cortical development.
AB  - Radial glial (RG) cells serve as stem cells to produce new born neurons and
      scaffolds for neuronal migration during corticogenesis. After neurogenesis and
      migration are completed, most RG cells transform into astrocytes. However, the
      mechanisms that determine how RG cells are transformed into astrocytes are not
      well understood. Using nestin as a specific marker for both RG cells and
      astrocytes, we found that loss of LXRbeta caused a reduction in the level of RG
      fibers and increase in the astrocytes. At the same time, we showed that the level
      of brain lipid-binding protein (BLBP), a RG-specific protein, was lower in the
      LXRbeta knockout (LXRbeta(-/-)) mice than in the wild type (WT) littermates from
      E18.5 to P14, a time period when most of RG cells are transformed into
      astrocytes. However, loss of LXRbeta induced significant increase in the number
      of GFAP labeled astrocytes in the cerebral cortex. An increase of the
      transformation of RG cells into astrocytes in LXRbeta(-/-) mice was further
      confirmed by the increased percentage of BLBP and GFAP double stained cells in
      the total BLBP positive cells of the Layer I and Layers V-VI. TGF-beta1 and Smad4
      are thought to be involved in the transformation of RG cells into astrocytes. The
      expression levels of TGF-beta1mRNA and Smad4 mRNA were significantly higher in
      the cerebral cortex of LXRbeta(-/-) mice than that in the WT littermates at P2
      and P7, but by P10 and P14, mRNA levels had normalized and no differences were
      observed between WT and LXRbeta(-/-) mice. Taken together, our findings suggest
      that loss of LXRbeta accelerates the transformation of RG cells into astrocytes
      and that this acceleration may be correlated to higher levels TGF-beta1 and Smad4
      in the cerebral cortex between P2 and P7.

PMID- 24662374
TI  - Ferritin H gene deletion in the choroid plexus and forebrain results in
      hydrocephalus.
AB  - Ferritin H, the major iron storage protein, has essential functions in early
      embryonic development as well as in adult liver and intestine. To address the
      question whether ferritin H has similarly essential functions in the brain we
      used the Cre/loxP system to generate mice with a forebrain-specific inactivation
      of the ferritin H gene. Ferritin H deficiency in most cells of the forebrain
      including cells of the choroid plexus caused accumulation of cerebrospinal fluid
      in the lateral ventricles and the subarachnoid space. Brain tissue iron content
      was unchanged.

PMID- 24662375
TI  - Economic trends from 2003 to 2010 for perioperative myocardial infarction: a
      retrospective, cohort study.
AB  - BACKGROUND: Perioperative myocardial infarction (PMI) is a major surgical
      complication that is costly and causes much morbidity and mortality. Diagnosis
      and treatment of PMIs have evolved over time. Many treatments are expensive but
      may reduce ancillary expenses including the duration of hospital stay. The time
      dependent economic impact of novel treatments for PMI remains unexplored. The
      authors thus evaluated absolute and incremental costs of PMI over time and
      discharge patterns. METHODS: Approximately 31 million inpatient discharges were
      analyzed between 2003 and 2010 from the California State Inpatient Database. PMI
      was defined using International Classification of Diseases, Ninth Revision,
      Clinical Modification codes. Propensity matching generated 21,637 pairs of
      comparable patients. Quantile regression modeled incremental charges as the
      response variable and year of discharge as the main predictor. Time trends of
      incremental charges adjusted to 2012 dollars, mortality, and discharge
      destination was evaluated. RESULTS: Median incremental charges decreased annually
      by $1,940 (95% CI, $620 to $3,250); P < 0.001. Compared with non-PMI patients,
      the median length of stay of patients who experienced PMI decreased significantly
      over time: yearly decrease was 0.16 (0.10 to 0.23) days; P < 0.001. No mortality
      differences were seen; but over time, PMI patients were increasingly likely to be
      transferred to another facility. CONCLUSIONS: Reduced incremental cost and
      unchanged mortality may reflect improving efficiency in the standard management
      of PMI. An increasing fraction of discharges to skilled nursing facilities seems
      likely a result from hospitals striving to reduce readmissions. It remains
      unclear whether this trend represents a transfer of cost and risk or improves
      patient care.

PMID- 24662376
TI  - Accuracy of transthoracic lung ultrasound for diagnosing anesthesia-induced
      atelectasis in children.
AB  - BACKGROUND: The aim of this study was to test the accuracy of lung sonography
      (LUS) to diagnose anesthesia-induced atelectasis in children undergoing magnetic
      resonance imaging (MRI). METHODS: Fifteen children with American Society of
      Anesthesiology's physical status classification I and aged 1 to 7 yr old were
      studied. Sevoflurane anesthesia was performed with the patients breathing
      spontaneously during the study period. After taking the reference lung MRI
      images, LUS was carried out using a linear probe of 6 to 12 MHz. Atelectasis was
      documented in MRI and LUS segmenting the chest into 12 similar anatomical
      regions. Images were analyzed by four blinded radiologists, two for LUS and two
      for MRI. The level of agreement for the diagnosis of atelectasis among observers
      was tested using the kappa reliability index. RESULTS: Fourteen patients
      developed atelectasis mainly in the most dependent parts of the lungs. LUS showed
      88% of sensitivity (95% CI, 74 to 96%), 89% of specificity (95% CI, 83 to 94%),
      and 88% of accuracy (95% CI, 83 to 92%) for the diagnosis of atelectasis taking
      MRI as reference. The agreement between the two radiologists for diagnosing
      atelectasis by MRI was very good (kappa, 0.87; 95% CI, 0.72 to 1; P < 0.0001) as
      was the agreement between the two radiologists for detecting atelectasis by LUS
      (kappa, 0.90; 95% CI, 0.75 to 1; P < 0.0001). MRI and LUS also showed good
      agreement when data from the four radiologists were pooled and examined together
      (kappa, 0.75; 95% CI, 0.69 to 0.81; P < 0.0001). CONCLUSION: LUS is an accurate,
      safe, and simple bedside method for diagnosing anesthesia-induced atelectasis in
      children.

PMID- 24662377
TI  - Changes in biosynthesis and metabolism of glutathione upon ochratoxin A stress in
      Arabidopsis thaliana.
AB  - Ochratoxin A (OTA) is one of the most toxic mycotoxins, which is toxic to plants
      and simulates oxidative stress. Glutathione is an important antioxidant in plants
      and is closely associated with detoxification in cells. We have previously shown
      that OTA exposure induces obvious expression differences in genes associated with
      glutathione metabolism. To characterize glutathione metabolism and understand its
      role in OTA phytotoxicity, we observed the accumulation of GSH in the detached
      leaves of Arabidopsis thaliana under OTA treatment. OTA stimulated a defense
      response through enhancing glutathione-S-transferase, glutathione peroxidase,
      glutathione reductase activities, and the transcript levels of these enzymes were
      increased to maintain the total glutathione content. Moreover, the level of
      oxidized glutathione (GSSG) was increased and the ascorbate-glutathione cycle
      fluctuated in response to OTA. The depletion of glutathione using buthionine
      sulfoximine (BSO, inhibitor of glutamate-cysteine ligase) had no profound effect
      on OTA toxicity, as glutathione was regenerated through the ascorbate-glutathione
      cycle to maintain the total glutathione content. The ROS, MDA and GSH
      accumulation was significantly affected in the mutant gsh1, gr1 and gpx2 after
      treatment with OTA, which indicated that glutathione metabolism is directly
      involved in the oxidative stress response of Arabidopsis thaliana subjected to
      OTA. In conclusion, date demonstrate that glutathione-associated metabolism is
      closely related with OTA stress and glutathione play a role in resistance of
      Arabidopsis subjected to OTA. 

PMID- 24662378
TI  - Dendritic cells: TLR agonists trigger rapid metabolic changes.

PMID- 24662379
TI  - Immunogenetics: tracking immune activity across the genome.

PMID- 24662380
TI  - Tumour immunology: inflaming tumour spread.

PMID- 24662388
TI  - The sensory immune system: a neural twist to the antigenic discontinuity theory.

PMID- 24662387
TI  - Democratizing systems immunology with modular transcriptional repertoire
      analyses.
AB  - Individual elements that constitute the immune system have been characterized
      over the few past decades, mostly through reductionist approaches. The
      introduction of large-scale profiling platforms has more recently facilitated the
      assessment of these elements on a global scale. However, the analysis and the
      interpretation of such large-scale datasets remains a challenge and a barrier for
      the wider adoption of systems approaches in immunological and clinical studies.
      In this Innovation article, we describe an analytical strategy that relies on the
      a priori determination of co-dependent gene sets for a given biological system.
      Such modular transcriptional repertoires can in turn be used to simplify the
      analysis and the interpretation of large-scale datasets, and to design targeted
      immune fingerprinting assays and web applications that will further facilitate
      the dissemination of systems approaches in immunology.

PMID- 24662389
TI  - Extracellular GTP is a potent water-transport regulator via aquaporin 5 plasma
      membrane insertion in M1-CCD epithelial cortical collecting duct cells.
AB  - BACKGROUND/AIMS: Extracellular GTP is able to modulate some specific functions in
      neuron, glia and muscle cell models as it has been demonstrated over the last two
      decades. In fact, extracellular GTP binds its specific plasma membrane binding
      sites and induces signal transduction via [Ca(2+)]i increase. We demonstrate, for
      the first time, that extracellular GTP is able to modulate cell swelling in M1
      CCD cortical collecting duct epithelial cells via upregulation of aquaporin 5
      (AQP5) expression. METHODS: We used videoimaging, immunocitochemistry, flow
      cytometry, confocal techniques, Western blotting and RT-PCR for protein and gene
      expression analysis, respectively. RESULTS: We demonstrate that AQP5 mRNA is up
      regulated 7 h after the GTP exposure in the cell culture medium, and its protein
      level is increased after 12-24 h. We show that AQP5 is targeted to the plasma
      membrane of M1-CCD cells, where it facilitates cell swelling, and that the GTP
      dependent AQP5 up-regulation occurs via [Ca(2+)]i increase. Indeed, GTP induces
      both oscillating and transient [Ca(2+)]i increase, and specifically the
      oscillating kinetic appears to be responsible for blocking cell cycle in the S
      phase while the [Ca(2+)]i influx, with whatever kinetic, seems to be responsible
      for inducing AQP5 expression. CONCLUSION: The role of GTP as a regulator of AQP5
      mediated water transport in renal cells is of great importance in the physiology
      of renal epithelia, due to its possible physiopathological implications. GTP
      dependent AQP5 expression could act as osmosensor. In addition, the data
      presented here suggest that GTP might play the same role in other tissues where
      rapid water transport is required for cell volume regulation and maintenance of
      the homeostasis.

PMID- 24662390
TI  - Molecular cloning, expression, and signaling pathway of four melanin
      concentrating hormone receptors from Xenopus tropicalis.
AB  - Melanin-concentrating hormone (MCH) mainly regulates feeding in mammals and
      pigmentation in teleosts. It acts via two G-protein-coupled receptors, MCH
      receptor 1 (MCHR1) and MCHR2. Although many studies exploring the MCH system in
      teleosts and mammals have been carried out, studies on other organisms are
      limited. In this study, we cloned and characterized four MCHR subtypes from the
      diploid species Xenopus tropicalis (X-MCHRs; X-MCHR1a, R1b, R2a, and R2b).
      According to a phylogenetic tree of the X-MCHRs, X-MCHR1a and R2a are close to
      mammalian MCHRs, while X-MCHR1b and R2b are close to teleostean MCHRs. We
      previously reported that the G-protein coupling capacity of the MCHR subtypes
      differed between mammals (R1: Galphai/o and Galphaq; R2: Galphaq) and teleosts
      (R1: Galphaq; R2: Galphai/o and Galphaq) in mammalian cell-based assays. By using
      Ca(2+) mobilization assays with pertussis toxin in CHO dhfr(-) cells, we found
      that X-MCHR1a promiscuously coupled to both Galphai/o and Galphaq, while X-MCHR1b
      and R2a exclusively coupled to Galphaq. However, no Ca(2+) influx was detected in
      cells transfected with X-MCHR2b. Reverse transcription-PCR showed that the X-MCHR
      mRNAs were expressed in various tissues. In particular, both X-MCHR1b and R2b
      were exclusively found in melanophores of the dorsal skin. In skin pigment
      migration assays, melanophores were weakly aggregated at low concentrations but
      dispersed at high concentrations of MCH, suggesting possible interactions between
      X-MCHR1b and R2b for the regulation of body color. These findings demonstrate
      that X. tropicalis has four characteristic MCHRs and will be useful for
      elucidating the nature of MCHR evolution among vertebrates. 

PMID- 24662391
TI  - Arginine vasotocin regulates social ascent in the African cichlid fish
      Astatotilapia burtoni.
AB  - Neuropeptides modulate many aspects of behavior and physiology in a broad range
      of animals. Arginine vasotocin (AVT) is implicated in mediating social behavior
      in teleost fish, although its specific role varies between species, sexes, life
      stages, and social context. To investigate whether the effects of AVT on behavior
      depend on social context, we used the African cichlid fish Astatotilapia burtoni,
      which is well-known for its remarkable behavioral plasticity. We
      pharmacologically manipulated the AVT system in established socially dominant and
      subordinate A. burtoni males, as well as in males ascending to dominance status
      in a socially unstable environment. Our results show that exogenous AVT causes a
      stress response, as evidenced by reduced behavioral activity and increased
      circulating levels of cortisol in established dominant and subordinate males.
      Administration of the AVT antagonist Manning compound, on the other hand, did not
      affect established subordinate or dominant males. However, AVT antagonist-treated
      males ascending from subordinate to dominant status exhibited reduced aggressive
      and increased courtship behavior compared to vehicle-treated animals. Finally, we
      measured circulating cortisol levels and brain gene expression levels of AVT and
      its behaviorally relevant V1a2 receptor in all three social phenotypes and found
      that plasma cortisol and mRNA levels of both genes were increased in ascending
      males compared to dominant and subordinate males. Our results provide a more
      detailed understanding of the role of the AVT system in the regulation of complex
      behavior in a dynamically changing social environment. 

PMID- 24662392
TI  - Prolactin is a major inhibitor of hepatic Leptin A synthesis and secretion:
      studies utilizing a homologous Leptin A ELISA in the tilapia.
AB  - The present study identifies regulatory interactions between leptin A (LepA) and
      the pituitary hormone prolactin (PRL). In order to measure tilapia (Oreochromis
      mossambicus) LepA, an enzyme-linked immunosorbent assay (ELISA) utilizing a
      rabbit polyclonal antibody specific to tilapia LepA was first developed. The
      antibody shows strong cross reactivity to recombinant tilapia LepA (rtLepA), and
      a corresponding 16kDa protein in both tilapia and striped bass plasma, but not to
      recombinant human leptin (rhLep). The assay has a linear detection range of 0.25
      1000nM, with intra- and interassay variability of 9% and 16%, respectively.
      Plasma LepA levels measured in tilapia ranged from 0.8 to 3.9nM, similar to that
      found for other vertebrates. Hypophysectomy (Hx) increased circulating LepA and
      lepa mRNA levels in the liver, the dominant source of hormone production.
      Adminstration of ovine PRL (oPRL, 5MUg/g BW) to Hx fish restored circulating LepA
      and hepatic lepa mRNA levels to those of control fish. Additionally, oPRL reduced
      lepa mRNA levels in a dose-dependent fashion in cultured hepatocytes following an
      18h incubation. Previous work in our lab indicates that rhLep stimulates PRL
      release in vitro from tilapia pituitaries. Here, both rtLepA and rhLep (0.5MUg/g
      BW) increased mRNA expression of tilapia prolactin mRNAs (prl1, prl2) in the
      pituitary in vivo. These results demonstrate that LepA enhances pituitary
      prolactin synthesis and release, while PRL in turn inhibits hepatic leptin
      secretion and synthesis in teleosts. We postulate this regulatory interaction may
      be necessary for mobilizing energy reserves during acute hyperosmotic adaptation.

PMID- 24662393
TI  - Reis-Bucklers corneal dystrophy: a reappraisal using in vivo and ex vivo imaging
      techniques.
AB  - PURPOSE: To characterize the phenotype of Reis-Bucklers corneal dystrophy (RBCD)
      using in vivo and ex vivo imaging techniques. METHODS: Five RBCD patients with
      penetrating keratoplasty (PK) were enrolled. Before surgery, all patients
      underwent a complete ophthalmological examination including slitlamp
      biomicroscopy, in vivo confocal microscopy (IVCM) and anterior segment (AS)
      optical coherence tomography (OCT). After PK, corneal buttons were examined by
      light and transmission electron microscopy (TEM). Correlations between in vivo
      and ex vivo images were analyzed. RESULTS: In all cases, irregular geographic
      like subepithelial gray-white opacities were observed in the central and mid
      peripheral cornea. AS-OCT images of the cornea of all patients revealed
      hyperreflective homogeneous and continuous deposits concentrated at the level of
      Bowman's layer and anterior stroma. Using IVCM, a highly reflective irregular
      amorphous material was observed from intermediate epithelial cells to the
      anterior stroma. Sparse deposits of highly reflective material were also detected
      in the posterior stroma. TEM showed in all specimens basal epithelial cells
      containing small vesicles with rod-shaped dense material. CONCLUSIONS: IVCM and
      AS-OCT may be a useful adjunct to biomicroscopy for the diagnosis and management
      of RBCD. The correlations between the different in vivo and ex vivo imaging
      techniques emphasize the hypothesis of an epithelial origin for RBCD.

PMID- 24662394
TI  - IBD and health-related quality of life -- discovering the true impact.
AB  - BACKGROUND AND AIMS: Although inflammatory bowel diseases (IBD) significantly
      impact the patient's quality of life, no European-level data exists on patients'
      perspectives. The primary objective of this survey was to obtain an international
      perspective of the impact of IBD on patients' lives. Secondary objectives
      included obtaining a better understanding of the quality of care, access to care,
      and differences between countries, age groups, and sub-groups of IBD. METHODS:
      The survey questionnaire consisted of 52 questions in six categories. The survey
      was translated into ten languages, tested on volunteers, and promoted across 25
      national IBD associations. Data was collected anonymously online, and
      participation was optional. RESULTS: 4670 patients completed the survey. Most
      respondents received a final diagnosis within a year from noticing first
      symptoms, but 67% had to visit emergency clinic at least once before diagnosis.
      85% had been hospitalized in the last five years. 64% felt that
      gastroenterologists should ask more probing questions and 54% that they did not
      get to tell something potentially important to their physician. Most respondents
      experienced symptoms weekly also in remission. Most had been absent from work due
      to IBD and 24% had received unfair comments about their work performance. 45%
      felt that IBD had negatively affected their performance in educational settings.
      CONCLUSIONS: The results of this survey can be used in defining strategic
      priorities and planning projects and awareness raising activities. The unmet
      needs of IBD patients can be better demonstrated and communicated to the public,
      health service managers and politicians.

PMID- 24662395
TI  - Clinical features and course of ulcerative colitis diagnosed in asymptomatic
      subjects.
AB  - BACKGROUND AND AIMS: Although some ulcerative colitis (UC) patients are diagnosed
      when they do not have any UC-related symptoms, clinical features and prognosis of
      UC diagnosed in asymptomatic patients remain unclear. METHODS: Data for UC
      patients who were asymptomatic at diagnosis were retrospectively reviewed from
      the IBD database of the Asan Medical Center. The clinical characteristics and
      prognosis of those patients were analyzed and compared with matched (1:4)
      symptomatic UC patients. RESULTS: Only nineteen asymptomatic UC patients (1.1%)
      were identified from 1665 UC patients. The proportion of males was 78.9% (n=15),
      and their median age at diagnosis was 48 years (range, 34-71 years). At
      diagnosis, proctitis was noted in 11 patients (57.9%), left-sided colitis in 4
      (21.1%), extensive colitis in 0 (0%), and atypical distribution in 4 (21.1%). The
      5-year cumulative probability of symptom development was 68.5% (95% confidence
      interval [CI], 62.8%-74.2%). After UC diagnosis, oral 5-aminisalicylic acid (ASA)
      and topical 5-ASA were used in 14 (73.7%) and 16 (84.2%) patients, respectively.
      During follow-up (3.7-year median for asymptomatic patients versus 3.7-year
      median for symptomatic patients; P=0.961), the 5-year cumulative probability of
      corticosteroids (23.7% versus 57.1%; P=0.022) and azathioprine (0% versus 24.7%;
      P=0.003) use was higher in symptomatic patients than in asymptomatic patients.
      CONCLUSIONS: The frequency of asymptomatic UC patients was 1.1% in our UC patient
      cohort. A majority of these patients became symptomatic during follow-up.
      Asymptomatic UC patients at diagnosis appear to have a better prognosis than
      symptomatic UC patients.

PMID- 24662396
TI  - Prospective validation study of the International Classification of Functioning,
      Disability and Health score in Crohn's disease and ulcerative colitis.
AB  - BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) may result in disability.
      We aim to validate a novel scoring system for the IBD disability index (IBD-DI),
      and identify predictors of disability and its correlation with work absenteeism.
      METHODS: This prospective IBD ambulatory clinic cohort study measured IBD-DI,
      Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) or partial Mayo
      score (pMayo) for ulcerative colitis (UC), IBDQ quality-of-life, and Work
      Productivity and Activity Impairment. Negative IBD-DI represented greater
      disability. Validation tests were performed and predictors and extent of work
      absenteeism were determined. RESULTS: 166 consecutive subjects were recruited (75
      CD, 41 UC, 50 controls). IBD-DI correlated with CDAI (r=-0.77, P<0.001), pMayo
      (r=-0.82, P<0.001) and IBDQ (r=0.86, P<0.001). IBD-DI differentiated CD, and UC
      from controls (medians -7, -4, +10; P<0.001) with a score of >3.5 identifying
      controls with 94% sensitivity and 83% specificity (area-under-curve 0.92). Stable
      patients had unchanged IBD-DI (P=ns) but not in those who relapsed (P<0.001).
      Intraclass correlation was 0.89 and Cronbach's alpha of internal consistency was
      0.94. Diagnosis age, sex, phenotype, perianal disease, prior surgery, steroid-use
      and disease duration did not influence the IBD-DI but active use of biological
      agents significantly reduced disability (P=0.03). 21.6% of IBD patients had
      moderate-severe disability equating to missing >25% of work hours in the previous
      week. Multivariate analysis identified that only IBD-DI to be predictive of
      unemployment status (OR: 0.94; 95% CI: 0.89-0.99). CONCLUSIONS: The IBD-DI is a
      valid tool measuring disability in both CD and UC and correlates with workforce
      participation. It is a potential useful tool in the assessment of participation
      restriction and activity limitation. TRIAL REGISTRATION: ACTRN12613000903785.

PMID- 24662397
TI  - Long-term functional outcome after ileal pouch anal anastomosis in 191 patients
      with ulcerative colitis.
AB  - BACKGROUND: A long-lasting good functional outcome of the pelvic pouch and a
      subsequent satisfying quality of life (QoL) are mandatory. Long-term functional
      outcome and QoL in a single-center cohort were assessed. PATIENTS AND METHODS: A
      questionnaire was sent to all patients with an IPAA for UC, operated between 1990
      and 2010 in our department. Pouch function was assessed using the Oresland Score
      (OS) and the 'Pouch Functional Score' (PFS). QoL was assessed using a Visual
      Analogue Score (VAS). RESULTS: 250 patients (42% females) with a median age at
      surgery of 38 years (interquartile range (IQR): 29-48 years) underwent
      restorative proctocolectomy. Median follow-up was 11 years (IQR: 6-17 years).
      Response rate was 81% (n=191). Overall pouch function was satisfactory with a
      median OS of 6/15 (IQR: 4-8) and a median PFS of 6/30 (IQR: 3-11). 24-hour bowel
      movement is limited to 8 times in 68% of patients (n=129), while 55 patients
      (29%) had less than 6 bowel movements. 12 patients (6.5%) were regularly
      incontinent for stools, while 154 patients (82%) reported a good fecal
      continence. Fecal incontinence during nighttime was more common (n=72, 39%).
      Pouch function had little impact on social activity (4/10; IQR: 2-6) and on
      professional activity (3/10; IQR: 1-6). 172 patients (90%) reported to experience
      an overall better health condition since their operation. The OS and the PFS
      correlated well (Pearson's correlation coefficient=0.83). Overall pouch function
      was stable over time. CONCLUSION: Majority of patients report a good pouch
      function on the long-term with limited impact on QoL.

PMID- 24662398
TI  - Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in
      hypercholesterolemic, statin-treated Japanese patients at high cardiovascular
      risk--primary results from the phase 2 YUKAWA study.
AB  - BACKGROUND: YUKAWA is a 12-week, randomized, double-blind, placebo-controlled,
      phase 2 study evaluating the efficacy and safety of evolocumab (AMG 145) in
      statin-treated Japanese patients at high cardiovascular risk. METHODS AND
      RESULTS: 310 eligible patients receiving stable statin (+/-ezetimibe) therapy
      were randomized to 1 of 6 treatments: placebo every 2 weeks (Q2W) or monthly
      (QM), evolocumab 70 mg or 140 mg Q2W, or evolocumab 280 mg or 420 mg QM. The
      primary endpoint was the percentage change from baseline in low-density
      lipoprotein cholesterol (LDL-C) measured by preparative ultracentrifugation (UC).
      Secondary endpoints included percentage changes in other lipid parameters and the
      proportion of patients with LDL-C <1.8 mmol/L. Mean (SD) age was 62 (10) years;
      37% were female; and the mean (SD) baseline LDL-C was 3.7 (0.5) mmol/L (by UC).
      Mean (SE) changes vs. placebo in LDL-C were greatest in the high-dose groups: 
      68.6 (3.0) % and -63.9 (3.2) % with 140 mg Q2W and 420 mg QM dosing,
      respectively. Up to 96% of evolocumab-treated patients achieved LDL-C <1.8
      mmol/L. Adverse events (AEs) were more frequent in evolocumab (51%) vs. placebo
      (38%) patients; 4 patients taking evolocumab discontinued treatment because of an
      AE. There were no significant differences in AE rates based on dose or dose
      frequency. CONCLUSIONS: In Japanese patients at high cardiovascular risk with
      hypercholesterolemia on stable statin therapy, evolocumab significantly reduced
      LDL-C and was well tolerated during this 12-week study.

PMID- 24662399
TI  - First clinical trial of a self-expandable transcatheter heart valve in Japan in
      patients with symptomatic severe aortic stenosis.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) may be a viable
      solution for inoperable or high-risk patients with aortic stenosis (AS),
      providing the benefit of valve replacement without the associated risks of
      surgery. METHODS AND RESULTS: The prospective, multicenter MDT-2111 Japan Trial
      evaluated the efficacy and safety of a self-expandable TAV in patients with
      severe AS. A total of 55 patients were enrolled (October 2011 to October 2012).
      Mean age was 82.5+/-5.5 years; 30.9% male, 100% NYHA III/IV, and STS 8.0+/-4.2%.
      At 6 months, 91.7% of the iliofemoral patients had met the primary endpoint (an
      improvement of at least 1 NYHA class and an effective orifice area >1.2 cm(2) for
      iliofemoral patients). For all patients, freedom from all-cause mortality at 6
      months was 90.8%. At 30 days, the Kaplan-Meier rate of major vascular
      complications was 10.9%, the rate of permanent pacemaker implantation was 22.2%
      and the rate of major stroke was 3.7%. The incidences of paravalvular
      regurgitation for all implanted patients at 6 months were: 38.3% (none), 25.5%
      (trace), 31.9% (mild), 4.3% (moderate), and 0.0% (severe). CONCLUSIONS: This is
      the first study to evaluate a self-expandable TAV in a Japanese patient
      population. The data show successful achievement of the study's primary objective
      and demonstrate the functional and anatomical effectiveness of the MDT-2111 TAV
      system.

PMID- 24662400
TI  - Nationwide survey of catheter ablation for atrial fibrillation: the Japanese
      Catheter Ablation Registry of Atrial Fibrillation (J-CARAF)--report of 1-year
      follow-up.
AB  - BACKGROUND: A nationwide survey of catheter ablation for atrial fibrillation (AF)
      was conducted in Japan to determine the mid-term performance of the therapy from
      analysis of the 1-year outcome of registered patients. METHODS AND RESULTS: A
      total of 2,137 patients who underwent AF ablation in September 2011 and March
      2012 were initially registered. In 2013, the 1-year follow-up data of 1,208
      patients (56.5% of 2,137) from 119 centers were collected. Average age was 61.9+/
      10.7 years. Patients with paroxysmal AF (PAF) constituted 64.3%. Persistent AF
      (pAF) and long-standing pAF (LS-pAF) were 20.4% and 15.3%, respectively. For all
      patients, 76.7% underwent their first AF ablation. At 1 year after AF ablation,
      70.9%, 61.4%, and 56.2% of PAF, pAF, and LS-pAF patients, respectively, were free
      from AF or clinical/partial success (PAF vs. pAF or LS-pAF: P<0.01). Re-ablation
      was performed in 11.3%, 16.3%, and 17.3%, respectively. Multivariate logistic
      regression analysis revealed that procedure time (odds ratio [OR] 0.82, P=0.000),
      and results of AF induction test (OR 1.36, P<0.02) were significantly related to
      successful outcome. CONCLUSIONS: Approximately 70% of PAF and 60% of nonPAF
      patients were free from AF recurrence or had clinical/partial success status.
      Shorter procedure time and elimination of AF inducibility were independent
      predictors of mid-term success of AF ablation.

PMID- 24662401
TI  - In-hospital clinical outcomes of elderly patients (>=80 years) undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: The clinical outcomes of elderly patients (>=80 years old) undergoing
      percutaneous coronary intervention (PCI) has not been well established, despite
      recent advances in both devices and techniques. METHODS AND RESULTS: We recruited
      patients from the SHINANO Registry, a prospective, observational, multicenter,
      cohort study. From August 2012 to July 2013, a total of 1,923 consecutive
      patients with 2,250 elective/urgent PCIs (2,105 admissions) (mean age, 71+/-11
      years; >=80 years, 23%; men, 77%) were enrolled. The primary endpoint was
      procedural success. The secondary endpoints were in-hospital death and in
      hospital major adverse cardiovascular events (MACE). The procedural success rate
      was significantly lower (83.7% vs. 89.1%, P=0.0001), and the rates of in-hospital
      mortality and MACE were significantly higher in elderly than in non-elderly
      patients (3.6% vs. 1.5%, P=0.005; 4.4% vs. 2.3%, P=0.016, respectively). For
      elective PCI, the rates of procedural success and in-hospital MACE were similar
      between groups (90.3% vs. 91.3%, P=0.65, 2.3% vs. 1.2%, P=0.2, respectively). On
      multivariate analysis, being elderly was not an independent predictor of
      procedural failure (OR, 1.15; CI, 0.81-1.61; P=0.43). CONCLUSIONS: In elderly
      patients, PCI is safe and feasible. The presence of comorbidities is a more
      important factor than age alone.

PMID- 24662402
TI  - Impact of introducing endovascular aneurysm repair on treatment strategy for
      repair of abdominal aortic aneurysm--National Hospital Organization network study
      in Japan.
AB  - BACKGROUND: The objective of the present study was to assess the hypothesis that
      the introduction of endovascular aneurysm repair (EVAR) into Japan has expanded
      the indication of abdominal aortic aneurysm (AAA) repair without increasing
      surgical mortality. METHODS AND RESULTS: From 10 national hospitals, we
      registered a total of 2,154 consecutive patients (Open surgery [OS]: n=1,577,
      EVAR: n=577) over 8 years, divided into 4 time periods: Group I (2005-2006:
      n=522), Group II (2007-2008: n=475), Group III (2009-2010: n=551), Group IV,
      (2011-2012: n=606). Mean age increased over the 4 time periods (P<0.0001). The
      incidences of COPD, smoking history, history of abdominal surgery and concomitant
      malignancy significantly increased as well, while the numbers of patients with
      preoperative shock or high ASA status reduced over time. The proportion of EVAR
      in AAA repair increased from: 0% in Group I, 11.6% in Group II, 41.0% in Group
      III, to 48.8% in Group IV (P<0.0001). Early mortality was 0.8% in the EVAR and
      3.4% in the OS (P<0.001) groups. Survival rates among the 4 groups free of all
      cause death and aneurysm-related death at 1 year were 92.1-96.3% (P=0.1555) and
      95.5-96.8% (P=0.9891), respectively. Multiple logistic regression analysis for
      surgical death failed to demonstrate survival advantage of EVAR over OS.
      CONCLUSIONS: Introduction of EVAR expanded the indication of AAA repair without
      increasing mortality, while high risk for anesthesia and emergency cases reduced
      over time. UMIN-CTR (UMIN000008345).

PMID- 24662403
TI  - A missense mutation in the sodium channel beta1b subunit reveals SCN1B as a
      susceptibility gene underlying long QT syndrome.
AB  - BACKGROUND: Long QT syndrome (LQTS) is associated with sudden cardiac death and
      the prolongation of the QT interval on the electrocardiogram. A comprehensive
      screening of all genes previously associated with this disease leaves 30% of the
      patients without a genetic diagnosis. Pathogenic mutations in the sodium channel
      beta subunits have been associated with cardiac channelopathies, including SCN4B
      mutations in LQTS. OBJECTIVE: To evaluate the role of mutations in the sodium
      channel beta subunits in LQTS. METHODS: We screened for mutations in the genes
      encoding the 5 sodium beta subunits (SCN1B isoforms a and b, SCN2B, SCN3B, and
      SCN4B) from 30 nonrelated patients who were clinically diagnosed with LQTS
      without mutations in common LQTS-related genes. We used the patch-clamp technique
      to study the properties of sodium currents and the action potential duration in
      human embryonic kidney and HL-1 cells, respectively, in the presence of beta1b
      subunits. RESULTS: The genetic screening revealed a novel mutation in the SCN1Bb
      gene (beta1bP213T) in an 8-year-old boy. Our electrophysiological analysis
      revealed that beta1bP213T increases late sodium current. In addition, beta1bP213T
      subtly altered Nav1.5 function by shifting the window current, accelerating
      recovery from inactivation, and decreasing the slow inactivation rate. Moreover,
      experiments using HL-1 cells revealed that the action potential duration
      significantly increases when the mutant beta1b was overexpressed compared with
      beta1bWT. CONCLUSION: These data revealed SCN1Bb as a susceptibility gene
      responsible for LQTS, highlighting the importance of continuing the search for
      new genes and mechanisms to decrease the percentage of patients with LQTS
      remaining without genetic diagnosis.

PMID- 24662404
TI  - What counts? For whom?: Cultural beacons and unexpected areas of programmatic
      impact.
AB  - The present article was motivated by our observations that (1) current methods
      for gathering data do not wholly capture program-related transformations, and (2)
      grassroots ways of knowing yield legitimate data and can enrich programmatic
      efforts and evaluations. Accordingly, our work seeks to leverage grassroots
      knowledge in order to both recognize and respect cultural beacons (CBs) -
      culturally embedded, user-defined aids for understanding program-related change.
      Simply, these inductively gathered, locally identified CBs illuminate what to
      measure and/or how to measure it. Our analysis of participatory evaluations from
      four international, social change interventions offers four sites for detecting
      CBs: material possessions, community landscape features, social behaviors, and
      community-inspired art. We examine the methodological and relational contexts
      that facilitate CB discovery, discuss unexpected areas of programmatic impact,
      and utilize lessons learned across projects to make suggestions for continued
      exploration of CBs in monitoring and evaluation design and practice. 

PMID- 24662405
TI  - An integrated photoluminescence sensing platform using a single-multi-mode fiber
      coupler-based probe.
AB  - We demonstrate an integrated fiber optic photoluminescence sensing platform using
      a novel single-multi-mode fiber coupler (SMFC)-based probe with high collection
      efficiency for fluorescence signals. The SMFC, prepared using fused biconical
      taper technology, not only transmits excitation light, but also collects and
      transmits fluorescence. The entire system does not use complex optical components
      and rarely requires optical alignment. The simple structure of the SMFC
      considerably improves the light transmission efficiency, signal-to-noise ratio,
      and sensitivity of the system. Theoretical and experimental results show that the
      proposed probe increases the collection efficiency by more than eight-fold
      compared with a bifurcated fiber probe. The performance of the proposed probe was
      experimentally evaluated by measuring the fluorescence spectra of well-known
      targets and a fresh Tall Fescue leaf. 

PMID- 24662406
TI  - Multi-sensor fusion for enhanced contextual awareness of everyday activities with
      ubiquitous devices.
AB  - In this paper, the authors investigate the role that smart devices, including
      smartphones and smartwatches, can play in identifying activities of daily living.
      A feasibility study involving N = 10 participants was carried out to evaluate the
      devices' ability to differentiate between nine everyday activities. The
      activities examined include walking, running, cycling, standing, sitting,
      elevator ascents, elevator descents, stair ascents and stair descents. The
      authors also evaluated the ability of these devices to differentiate indoors from
      outdoors, with the aim of enhancing contextual awareness. Data from this study
      was used to train and test five well known machine learning algorithms: C4.5,
      CART, Naive Bayes, Multi-Layer Perceptrons and finally Support Vector Machines.
      Both single and multi-sensor approaches were examined to better understand the
      role each sensor in the device can play in unobtrusive activity recognition. The
      authors found overall results to be promising, with some models correctly
      classifying up to 100% of all instances. 

PMID- 24662407
TI  - Fully distributed monitoring architecture supporting multiple trackees and
      trackers in indoor mobile asset management application.
AB  - A tracking service like asset management is essential in a dynamic hospital
      environment consisting of numerous mobile assets (e.g., wheelchairs or infusion
      pumps) that are continuously relocated throughout a hospital. The tracking
      service is accomplished based on the key technologies of an indoor location-based
      service (LBS), such as locating and monitoring multiple mobile targets inside a
      building in real time. An indoor LBS such as a tracking service entails numerous
      resource lookups being requested concurrently and frequently from several
      locations, as well as a network infrastructure requiring support for high
      scalability in indoor environments. A traditional centralized architecture needs
      to maintain a geographic map of the entire building or complex in its central
      server, which can cause low scalability and traffic congestion. This paper
      presents a self-organizing and fully distributed indoor mobile asset management
      (MAM) platform, and proposes an architecture for multiple trackees (such as
      mobile assets) and trackers based on the proposed distributed platform in real
      time. In order to verify the suggested platform, scalability performance
      according to increases in the number of concurrent lookups was evaluated in a
      real test bed. Tracking latency and traffic load ratio in the proposed tracking
      architecture was also evaluated. 

PMID- 24662408
TI  - Analyzing body movements within the Laban Effort Framework using a single
      accelerometer.
AB  - This article presents a study on analyzing body movements by using a single
      accelerometer sensor. The investigated categories of body movements belong to the
      Laban Effort Framework: Strong-Light, Free-Bound and Sudden-Sustained. All body
      movements were represented by a set of activities used for data collection. The
      calculated accuracy of detecting the body movements was based on collecting data
      from a single wireless tri-axial accelerometer sensor. Ten healthy subjects
      collected data from three body locations (chest, wrist and thigh) simultaneously
      in order to analyze the locations comparatively. The data was then processed and
      analyzed using Machine Learning techniques. The wrist placement was found to be
      the best single location to record data for detecting Strong-Light body movements
      using the Random Forest classifier. The wrist placement was also the best
      location for classifying Bound-Free body movements using the SVM classifier.
      However, the data collected from the chest placement yielded the best results for
      detecting Sudden-Sustained body movements using the Random Forest classifier. The
      study shows that the choice of the accelerometer placement should depend on the
      targeted type of movement. In addition, the choice of the classifier when
      processing data should also depend on the chosen location and the target
      movement. 

PMID- 24662410
TI  - Should adenocarcinoma of the esophagogastric junction be classified as esophageal
      cancer? Limited to Siewert type II, yes.

PMID- 24662409
TI  - A systematic review of the effects of resident duty hour restrictions in surgery:
      impact on resident wellness, training, and patient outcomes.
AB  - BACKGROUND: In 2003, the Accreditation Council for Graduate Medical Education
      (ACGME) mandated 80-hour resident duty limits. In 2011 the ACGME mandated 16-hour
      duty maximums for PGY1 (post graduate year) residents. The stated goals were to
      improve patient safety, resident well-being, and education. A systematic review
      and meta-analysis were performed to evaluate the impact of resident duty hours
      (RDH) on clinical and educational outcomes in surgery. METHODS: A systematic
      review (1980-2013) was executed on CINAHL, Cochrane Database, Embase, Medline,
      and Scopus. Quality of articles was assessed using the GRADE guidelines. Sixteen
      hour shifts and night float systems were analyzed separately. Articles that
      examined mortality data were combined in a random-effects meta-analysis to
      evaluate the impact of RDH on patient mortality. RESULTS: A total of 135 articles
      met the inclusion criteria. Among these, 42% (N = 57) were considered moderate
      high quality. There was no overall improvement in patient outcomes as a result of
      RDH; however, some studies suggest increased complication rates in high-acuity
      patients. There was no improvement in education related to RDH restrictions, and
      performance on certification examinations has declined in some specialties.
      Survey studies revealed a perception of worsened education and patient safety.
      There were improvements in resident wellness after the 80-hour workweek, but
      there was little improvement or negative effects on wellness after 16-hour duty
      maximums were implemented. CONCLUSIONS: Recent RDH changes are not consistently
      associated with improvements in resident well-being, and have negative impacts on
      patient outcomes and performance on certification examinations. Greater
      flexibility to accommodate resident training needs is required. Further erosion
      of training time should be considered with great caution.

PMID- 24662411
TI  - Long-term oncologic outcomes of robotic low anterior resection for rectal cancer:
      a comparative study with laparoscopic surgery.
AB  - OBJECTIVE: The aim of this study is to evaluate long-term oncologic outcomes of
      robotic surgery for rectal cancer compared with laparoscopic surgery at a single
      institution. BACKGROUND: Robotic surgery is regarded as a new modality to surpass
      the technical limitations of conventional surgery. Short-term outcomes of robotic
      surgery for rectal cancer were acceptable in previous reports. However, evidence
      of long-term feasibility and oncologic safety is required. METHODS: Between April
      2006 and August 2011, 217 patients who underwent minimally invasive surgery for
      rectal cancer with stage I-III disease were enrolled prospectively (robot, n =
      133; laparoscopy, n = 84). Median follow-up period was 58 months (range, 4-80
      months). Perioperative clinicopathologic outcomes, morbidities, 5-year survival
      rates, prognostic factors, and cost were evaluated. RESULTS: Perioperative
      clinicopathologic outcomes demonstrated no significant differences except for the
      conversion rate and length of hospital stay. The 5-year overall survival rate was
      92.8% in robotic, and 93.5% in laparoscopic surgical procedures (P = 0.829). The
      5-year disease-free survival rate was 81.9% and 78.7%, respectively (P = 0.547).
      Local recurrence was similar: 2.3% and 1.2% (P = 0.649). According to the
      univariate analysis, this type of surgical approach was not a prognostic factor
      for long-term survival. The patient's mean payment for robotic surgery was
      approximately 2.34 times higher than laparoscopic surgery. CONCLUSIONS: No
      significant differences were found in the 5-year overall, disease-free survival
      and local recurrence rates between robotic and laparoscopic surgical procedures.
      We concluded that robotic surgery for rectal cancer failed to offer any oncologic
      or clinical benefits as compared with laparoscopy despite an increased cost.

PMID- 24662412
TI  - SalA attenuates ischemia/reperfusion-induced endothelial barrier dysfunction via
      down-regulation of VLDL receptor expression.
AB  - BACKGROUND: Salvianolic acid A (SalA) has been shown to confer robust protection
      against endothelial injury. VLDL receptor is expressed at high levels on the
      endothelial surface, however its biological effect on endothelial cells has not
      yet been completely elucidated. Here, we investigated molecular effects of SalA
      on endothelial VLDL expression and barrier dysfunction under conditions of
      ischemia/reperfusion (IS/RP). METHODS: Human umbilical vein endothelial cells
      (HUVECs) treated with SalA were subjected to IS/RP stimulation. Endothelial
      permeability, ZO-1 distribution, actin cytoskeleton reorganization, and
      intracellular reactive oxygen species (ROS) generation were examined. The mRNA
      levels were tested by real-time RT-PCR and the protein levels were determined by
      immunoblot analysis. RESULTS: Pretreatment of HUVECs with SalA markedly
      attenuated IS/RP-induced endothelial hyperpermeability, discontinuous ZO-1
      staining, actin stress fiber formation, and intracellular ROS generation. IS/RP
      activated p38 MAPK signaling and enhanced VLDL receptor expression, and
      inactivation of p38 MAPK abolished increase of VLDL receptor expression.
      Furthermore, siRNA experiments showed that VLDL receptor was a crucial mediator
      of endothelial barrier dysfunction and intracellular ROS generation induced by
      IS/RP. Importantly, SalA effectively suppressed IS/RP-induced activation of p38
      MAPK signaling and increase of VLDL receptor expression. CONCLUSION: These
      results for the first time demonstrated that SalA protected against IS/RP-induced
      endothelial barrier dysfunction through suppression of VLDL receptor expression.

PMID- 24662413
TI  - Influence of dynamic obstruction and hypertrophy location on diastolic function
      in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a disease with marked genetic
      and phenotypic heterogeneity. It is well known that obstructive septal forms of
      this disease entail worse clinical outcome compared with nonobstructive septal
      and apical forms. The objective of this study was to analyze the differences in
      left ventricular diastolic function in different subgroups of HCMs and to assess
      the influence of the location of myocardial hypertrophy and the presence of
      dynamic obstruction on impairment of diastolic function and its correlation with
      the clinical status. METHODS: We studied 86 patients with HCM; 27 with the
      obstructive asymmetric septal type (OAS), 37 with the nonobstructive asymmetric
      septal type (NOAS) and 22 with apical hypertrophic cardiomyopathy (ApHCM).
      Patients underwent conventional and tissue Doppler echocardiography and were
      assessed applying the latest recommendations regarding diastolic dysfunction.
      Cardiac magnetic resonance was used to study the various morphologic subtypes and
      quantify left ventricular mass (LVM). RESULTS: The early diastolic annular
      velocity (e') was significantly lower in OAS with a median of 5 cm/s compared
      with NOAS with 7 cm/s and ApHCM with 7.5 cm/s (P = 0.0002), and the E/e' ratio
      was 8.5 in ApHCM, 10 in NOAS and 14 in OAS (P = 0.0001); no significant
      differences were found in LVM or maximal wall thickness. CONCLUSION: In HCM, the
      location of left ventricular hypertrophy and the presence of dynamic obstruction
      affect the degree of diastolic dysfunction; impairment is greater in patients
      with the OAS type, and markedly less in patients with apical involvement.

PMID- 24662414
TI  - Atrioventricular conduction after alcohol septal ablation for obstructive
      hypertrophic cardiomyopathy.
AB  - AIMS: Lesion of the atrioventricular conduction system is a well known adverse
      effect of alcohol septal ablation (ASA) in patients with obstructive hypertrophic
      cardiomyopathy (HCM). We assessed the atrioventricular conduction at long-term
      follow-up after ASA. METHODS: In patients with a pacemaker implanted for high
      grade atrioventricular block after ASA, the atrioventricular conduction was
      assessed prospectively by ECGs and 48-h Holter recordings. In the remaining
      patients, the atrioventricular conduction was analysed retrospectively for
      comparison. RESULTS: A total of 24 (28%) of 87 patients with obstructive HCM
      without a pacemaker at baseline had a pacemaker implanted due to high-grade
      atrioventricular block after ASA. Ten of these patients were not available for
      follow-up. Holter recordings in the remaining 14 patients revealed normalized
      atrioventricular conduction in 6 patients 6.2 years (range 2.1-9.4) after ASA.
      Patients with high-grade atrioventricular block at follow-up had longer PR
      intervals at baseline [205 ms (200-230)] than the rest of the cohort [180 ms (140
      200), P = 0.004] and a higher incidence of acute complete heart block (63 vs.
      15%; P = 0.007) during ASA. A PR interval of at least 200 ms at baseline was
      associated with higher prevalence of high-grade atrioventricular block at follow
      up (30 vs. 2%; P = 0.0013). The incidence of late-onset complete heart block was
      1.5% per year after ASA. CONCLUSION: We found normalized atrioventricular
      conduction at long-term follow-up, suggesting recovery in 6 of 14 patients with a
      pacemaker implanted in relation to ASA. Permanent atrioventricular conduction
      abnormalities were associated with baseline PR intervals of at least 200 ms and
      acute persistent complete heart block during ASA.

PMID- 24662415
TI  - Ranolazine for the prevention or treatment of atrial fibrillation: a systematic
      review.
AB  - The use of currently available antiarrhythmic drugs for atrial fibrillation is
      limited by their moderate efficacy and the considerable proarrhythmic risk.
      Ranolazine, an antianginal agent, has been reported to possess antiarrhythmic
      properties, resulting in a reduction of supraventricular and ventricular
      arrhythmias. We performed a systematic review of the clinical studies reporting
      the outcome of patients treated with ranolazine for the prevention or treatment
      of atrial fibrillation in various clinical settings. We searched PubMed and
      abstracts of major conferences for clinical studies using ranolazine, either
      alone or in combination with other antiarrhythmic agents for the prevention or
      treatment of atrial fibrillation. Ten relevant records were identified. These
      included both randomized trials and retrospective cohort studies concerning the
      use of ranolazine in different clinical settings; prevention of atrial
      fibrillation in patients with acute coronary syndrome, prevention as well as
      conversion of postoperative atrial fibrillation after coronary artery bypass
      grafting, conversion of recent-onset atrial fibrillation, sinus rhythm
      maintenance in drug-resistant recurrent atrial fibrillation and facilitation of
      electrical cardioversion in cardioversion-resistant patients. A beneficial,
      mostly modest effect of ranolazine was homogeneously reported in all clinical
      settings. There were no substantial proarrhythmic effects. No meta-analysis could
      be performed because for most of the clinical scenarios, there was only one study
      investigating the effect of ranolazine. Except for one large randomized trial,
      all the other studies were either relatively small randomized studies or
      retrospective cohort analyses, which in several cases lacked a control group.
      This systematic review indicates a modest beneficial effect of ranolazine
      administered for the prevention or treatment of atrial fibrillation across
      several clinical settings without substantial proarrhythmic risk. 

PMID- 24662416
TI  - HLA-A(*)02, gender and tobacco smoking, but not multiple sclerosis, affects the
      IgG antibody response against human herpesvirus 6.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central
      nervous system. Both genetic and environmental factors contribute to disease
      susceptibility and two viruses associated with MS are human herpesvirus (HHV)-6A
      and HHV-6B, together referred to as HHV-6. This study characterized the plasma
      IgG antibody response against HHV-6 in MS patients (n=446) and healthy controls
      (n=487), and the relationship between MS susceptibility factors and the anti-HHV
      6 response was investigated. In addition, 134 samples were further investigated
      for IgG against the early HHV-6 antigen p41. Antibody levels were measured with
      ELISA. The overall seroprevalence against HHV-6 was 90%, with no significant
      difference in positivity or levels between MS patients and controls.
      Interestingly, carriership of HLA-A(*)02 and tobacco smoking was associated with
      lower anti-HHV-6 IgG levels (p=0.0017 and p=0.026 respectively), whereas females
      sex was associated with higher levels (p=0.0090). No difference in IgG titers
      against p41 was observed between MS patients and controls. In conclusion, the IgG
      response against HHV-6 was associated with several factors that have previously
      been associated with MS susceptibility, possibly reflecting a relation between
      autoimmunity and how the immune system handles viral infections.

PMID- 24662417
TI  - Detection of donor-specific-antibodies by solid phase assay and its relevance to
      complement-dependent-lymphocytotoxicity cross-matching in kidney transplantation.
AB  - Presensitization against a broad array of HLA is associated with prolonged
      waiting times and inferior kidney allogaft survival. Although the use of solid
      phase assay (SPA) for the detection and characterization of anti-HLA antibodies
      provides greater sensitivity than complement-dependent lymphocytotoxicity (CDC)
      assay, it often detects donor specific antibodies (DSA) which turn out to be
      clinically irrelevant. Our data reinforce the concept that these two types of
      assays should be used in parallel for pre-and post-transplantation monitoring of
      anti-HLA antibodies in recipients of solid organ allografts.

PMID- 24662418
TI  - PBSC vs BM grafts with myeloablative conditioning for unrelated donor
      transplantation in adults with high-risk ALL.
AB  - Few studies are available that compare PBSC and BM from unrelated donors,
      especially in adult high-risk ALL. To determine which graft source is superior in
      adult high-risk ALL, we analyzed the long-term outcomes of 106 consecutive
      transplants from 8/8-matched or 7/8-matched unrelated donors (38 PBSC vs 68 BM).
      All patients received a uniform strategy of pre-transplant therapy, myeloablative
      conditioning and GVHD prophylaxis. At 5 years, PBSC transplants showed higher
      incidence of chronic GVHD than did BM transplants (74.3% vs 46.7%, P=0.001). PBSC
      transplants showed outcomes comparable to those of BM transplants for relapse
      (23.7% vs 28.1%), non-relapse mortality (18.4% vs 25.0%), disease-free survival
      (57.9% vs 46.9%) and OS (57.9% vs 50.0%). In a separate comparison of outcomes
      between the two graft sources according to the presence of a Ph chromosome, no
      significant advantage of PBSC over BM was found in both subgroups of patients.
      Our data suggest that the outcomes of unrelated donor transplantation are similar
      between PBSC and BM in adult high-risk ALL. Whether PBSC should be the preferred
      graft source for a specific subgroup of adult ALL needs to be further
      investigated. 

PMID- 24662419
TI  - Comparison of 1-day vs 2-day dosing of high-dose melphalan followed by autologous
      hematopoietic cell transplantation in patients with multiple myeloma.
AB  - High-dose melphalan at 200 mg/m(2) can be administered in 1 day or over 2
      consecutive days before autologous hematopoietic cell transplantation (HCT) for
      multiple myeloma (MM). Limited data exist on the comparison of the two dosing
      schedules. A retrospective study of 278 consecutive MM patients receiving high
      dose melphalan from January 2010 to December 2012 was conducted. Objectives were
      to compare the length of hospitalization, toxicity profile, response rates, PFS
      and OS. One hundred and eighty five patients received 2-day dosing and 93
      received 1-day dosing. The two end points of the 95% confidence interval (CI) for
      the difference did not exceed the preselected margin, therefore the length of
      hospitalization was considered equivalent. No significant differences were found
      for response rates, PFS and OS.  The toxicity profile was similar with the
      exception of more frequent ?grade 3 oral mucositis in the 2-day group (13.5% vs
      5.4%; odds ratio 3.07 (95% CI:1.11-8.48); P=0.03). High-dose melphalan, given
      either in 1 day or over 2 days, produced comparable treatment outcomes except for
      increased grade 3/4 mucositis in the 2-day regimen. One-day dosing could shorten
      the hospital stay by 1 day and may allow better resource utilization. 

PMID- 24662420
TI  - Etiology, clinical features and outcomes of pre-engraftment and post-engraftment
      bloodstream infection in hematopoietic SCT recipients.
AB  - We conducted an observational study to assess the etiology, clinical features and
      outcomes of bloodstream infection (BSI) in 172 hematopoietic SCT (HCST)
      recipients. One hundred episodes of BSI in the pre-engraftment period (early
      onset) were compared with 89 episodes in the post-engraftment phase (late onset).
      More patients with late-onset BSI received an allogeneic HSCT, had GVHD and had
      received corticosteroids, whereas patients with early-onset BSI were more likely
      to have neutropenia, severe mucositis and a central venous catheter (CVC) in
      place. CVC was the most frequent site of infection, followed by an endogenous
      source. Pneumonia and gastrointestinal infection were particularly frequent in
      late-onset BSI, whereas mucositis was more frequent in the early-onset group.
      Gram-positive organisms predominated over Gram negatives. Streptococcus
      pneumoniae was more frequent in patients with late-onset BSI. Patients with late
      onset BSI presented worse outcomes regarding septic shock, intensive care unit
      admission and early and overall case-fatality rates. Early-onset BSI was mainly
      related to the presence of neutropenia, mucositis and CVC, whereas late-onset BSI
      mainly affected severely immunosuppressed allogeneic HSCT recipients with GVHD
      and corticosteroids. Late-onset BSI caused high case-fatality rates. BSI due to
      S. pneumoniae was especially frequent late after transplantation. The development
      of better vaccination strategies is needed. 

PMID- 24662421
TI  - The feasibility of high-intensity interval exercise in obese adolescents.

PMID- 24662422
TI  - Growth of healthy term infants fed ready-to-feed and powdered forms of an
      extensively hydrolyzed casein-based infant formula: a randomized, blinded,
      controlled trial.
AB  - Extensively hydrolyzed formulas present a complex matrix subject to adverse
      conditions during manufacture that could influence growth and tolerance of
      infants fed these formulas. A masked, randomized, parallel growth study was
      conducted in infants fed a ready-to-feed (RTF) or powdered (PWD) form of an
      extensively hydrolyzed casein-based formula. Infants were enrolled between 0 and
      9 days and studied to 112 days of age. Growth, formula intake, and stool patterns
      were assessed. There were no significant differences between groups in weight,
      length, head circumference, or their respective gains. Tolerance was similar
      between groups except that the RTF group had greater formula intakes and passed
      more stools/day compared to the PWD group. This study demonstrates that the PWD
      formulation of this RTF formula supports similar growth and tolerance in infants
      during the first 4 months of life. 

PMID- 24662423
TI  - A microfluidic based in vitro model of synaptic competition.
AB  - Synaptic competition is widely believed to be central to the formation and
      function of neuronal networks, yet the underlying mechanisms are poorly
      described. To investigate synaptic competition in vitro, we have developed a
      novel two input pathway competition model using a 3-compartment microfluidic
      device. Axons from cultured rat cortical neurons from two different lateral
      compartments (inputs) innervate a common neuronal population in a separate
      central compartment. Inhibiting one input's activity, using the GABAAR agonist
      muscimol, resulted in increased synapse numbers and axon elongation of the
      opposing untreated (uninhibited) inputs in the central compartment. Time lapse
      imaging revealed that uninhibited inputs outgrew and outconnected their inhibited
      counterparts. This form of competition occurs during a sensitive period ending
      prior to 21 DIV and is NMDAR and CamKII dependent. Surprisingly, this form of
      plasticity was dependent on the age of the center compartment neurons but not of
      the competing inputs. 

PMID- 24662424
TI  - Amebic liver abscess: fine needle aspiration diagnosis.
AB  - OBJECTIVE: To describe the findings in fine needle aspiration (FNA) of an amebic
      liver abscess (ALA). STUDY DESIGN: Seven patients (6 men and 1 woman between 52
      and 60 years of age) treated for amebic dysentery with multiple liver lesions
      were selected for ultrasound (US)-guided FNA. The clinical differential diagnosis
      was malignancy. Abdominal US of the patients revealed multiple, variably sized,
      well-defined, hypoechoic, cystic liver lesions. FNA of these lesions was
      performed. RESULTS: Smears of the aspirated material showed necrotic material
      with mixed inflammatory cells and Entamoeba histolytica trophozoites consisting
      of round blue bodies with well-defined borders containing a single, eccentrically
      located nucleus with central karyosome and engulfed red blood cells in the
      cytoplasm. There were also Charcot-Leyden crystals. ALA was diagnosed.
      CONCLUSION: FNA can yield the correct diagnosis of ALA and allows early
      initiation of treatment. ALA should be considered in the differential diagnosis
      of space-occupying lesions of the liver.

PMID- 24662425
TI  - Variation in steroid hormone levels among Caribbean Anolis lizards: endocrine
      system convergence?
AB  - Variation in aggression among species can be due to a number of proximate and
      ultimate factors, leading to patterns of divergent and convergent evolution of
      behavior among even closely related species. Caribbean Anolis lizards are well
      known for their convergence in microhabitat use and morphology, but they also
      display marked convergence in social behavior and patterns of aggression. We
      studied 18 Anolis species across six ecomorphs on four different Caribbean
      islands to test four main hypotheses. We hypothesized that species differences in
      aggression would be due to species differences in circulating testosterone (T), a
      steroid hormone implicated in numerous studies across vertebrate taxa as a
      primary determinant of social behavior; more aggressive species were expected to
      have higher baseline concentrations of T and corticosterone. We further
      hypothesized that low-T species would increase T and corticosterone levels during
      a social challenge. Within three of the four island assemblages studied we found
      differences in T levels among species within an island that differ in aggression,
      but in the opposite pattern than predicted: more aggressive species had lower
      baseline T than the least aggressive species. The fourth island, Puerto Rico,
      showed the pattern of baseline T levels among species we predicted. There were no
      patterns of corticosterone levels among species or ecomorphs. One of the two
      species tested increased T in response to a social challenge, but neither species
      elevated corticosterone. Our results suggest that it is possible for similarities
      in aggression among closely related species to evolve via different proximate
      mechanisms. 

PMID- 24662426
TI  - Molecular basis for erythromycin-dependent ribosome stalling during translation
      of the ErmBL leader peptide.
AB  - In bacteria, ribosome stalling during translation of ErmBL leader peptide occurs
      in the presence of the antibiotic erythromycin and leads to induction of
      expression of the downstream macrolide resistance methyltransferase ErmB. The
      lack of structures of drug-dependent stalled ribosome complexes (SRCs) has
      limited our mechanistic understanding of this regulatory process. Here we present
      a cryo-electron microscopy structure of the erythromycin-dependent ErmBL-SRC. The
      structure reveals that the antibiotic does not interact directly with ErmBL, but
      rather redirects the path of the peptide within the tunnel. Furthermore, we
      identify a key peptide-ribosome interaction that defines an important relay
      pathway from the ribosomal tunnel to the peptidyltransferase centre (PTC). The
      PTC of the ErmBL-SRC appears to adopt an uninduced state that prevents
      accommodation of Lys-tRNA at the A-site, thus providing structural basis for
      understanding how the drug and the nascent peptide cooperate to inhibit peptide
      bond formation and induce translation arrest. 

PMID- 24662427
TI  - Slight alteration of the electroretinogram in mice lacking dystrophin dp71.
AB  - AIM: Most Duchenne muscular dystrophy patients and the mdx(Cv3) mouse strain,
      lacking expression of both dystrophins Dp260 and Dp71, show a high attenuation of
      the dark-adapted electroretinogram (ERG) b-wave amplitude, whereas mice lacking
      the expression of Dp260 show normal b-wave amplitude. Here, we completed our
      assessment of whether the sole absence of Dp71 affects the ERG. METHODS: Ganzfeld
      ERGs were performed on dark-adapted Dp71-null mice and littermates. Scotopic
      flash ERGs were recorded at light intensities from 3.10-(5) to 1 cd.s/m(2).
      Oscillatory potentials (OPs) were extracted at 1 cd.s/m(2). Photopic flash ERGs
      were recorded at 10 cd.s/m(2) after light adaptation. RESULTS: Dp71-null mice
      showed a slight but significant reduction in b-wave amplitudes, normal a-wave
      amplitudes and nonaffected implicit times of the scotopic ERGs. No changes were
      observed in the amplitudes and implicit times of the OPs and the photopic ERGs.
      CONCLUSIONS: Our results demonstrate that together both Dp71 and Dp260 are
      required for the generation of the ERG b-wave in mice.

PMID- 24662428
TI  - Vascular disease: Clearing the pipes via angiophagy.

PMID- 24662430
TI  - Stem cells: The renoprotective role of miR-126.

PMID- 24662433
TI  - Novel targets of antifibrotic and anti-inflammatory treatment in CKD.
AB  - Chronic kidney disease (CKD) is becoming a worldwide epidemic, driven largely by
      the dramatic rise in the prevalence of diabetes and obesity. Novel targets and
      treatments for CKD are, therefore, desperately needed-to both mitigate the burden
      of this disease in the general population and reduce the necessity for renal
      replacement therapy in individual patients. This Review highlights new insights
      into the mechanisms that contribute to CKD, and approaches that might facilitate
      the development of disease-arresting therapies for CKD. Particular focus is given
      to therapeutic approaches using antifibrotic agents that target the transforming
      growth factor beta superfamily. In addition, we discuss new insights regarding
      the roles of vascular calcification, the NADPH oxidase family, and inflammation
      in the pathogenesis of CKD. We also highlight a new understanding regarding
      kidney energy sensing pathways (AMPK, sirtuins, and mTOR) in a variety of kidney
      diseases and how they are linked to inflammation and fibrosis. Finally, exciting
      new insights have been made into the role of mitochondrial function and
      mitochondrial biogenesis in relation to progressive kidney disease. Prospective
      therapeutics based on these findings will hopefully renew hope for clinicians and
      patients in the near future. 

PMID- 24662436
TI  - Imaging: BOLD assessment--effects of RAAS inhibition in CKD.

PMID- 24662435
TI  - Nephrotoxic effects of designer drugs: synthetic is not better!
AB  - Designer drugs are synthetic, psychoactive substances with similar structures and
      activity to existing scheduled drugs or controlled chemical compounds. The use of
      these drugs is not generally considered illegal and they cannot be detected using
      standard toxicology tests--essentially they are considered to be 'legal highs'.
      Over the past several years, increasing numbers of designer drugs have become
      available. These drugs are classified as amphetamine derivatives,
      phenylpiperazine derivatives, synthetic cathinones, synthetic cannabinoids,
      phencyclidine derivatives and synthetic opioids. Although euphoria is the desired
      effect, neuropsychiatric and cardiac manifestations are frequently observed in
      individuals using these drugs at high doses or using drugs that are contaminated
      with other substances. Some designer drugs are also associated with adverse renal
      effects, including acute kidney injury from pigment nephropathy, acute tubular
      necrosis, obstructive nephropathy and hyponatraemia. The misuse of these drugs
      should be recognized and clinicians made aware of the potential for acute
      nephrotoxicity as the health burden of these compounds increases.

PMID- 24662437
TI  - That's cool!--Nebulization of thermolabile proteins with a cooled vibrating mesh
      nebulizer.
AB  - Despite contrary reports, heating inside the medication reservoir was observed
      for several vibrating mesh nebulizers, which may be detrimental when nebulizing
      biopharmaceuticals. In this study we evaluated different strategies to reduce
      reservoir heating during nebulization with a PARI eFlow(r) regarding cooling
      efficiency, impact on nebulizer performance and on protein stability after
      nebulization. Passive cooling was achieved by solution pre-cooling, overcharging
      of the reservoir with 1 mL additional solution or intermittent nebulization.
      Active cooling was realized with a micro Peltier element attached to the
      nebulizer reservoir. Passive cooling was most effective when the reservoir was
      overcharged with pre-cooled solution reducing the average reservoir temperature
      (TRES AVG) by 8.4 degrees C. Active cooling enabled nebulization at a constant
      reservoir temperature (TRES) as low as 15 degrees C. TRES manipulation had a
      linear impact on nebulizer performance. While the output rate decreased with
      decreasing TRES, the inhalable fraction increased resulting in an inhalable
      aerosol rate constant over a large TRES range. The effect on protein stability
      depended on the susceptibility to thermal stress and was predicted by Tm values.
      For lactic dehydrogenase and SM101, both exhibiting a Tm below 60 degrees C,
      cooling was protective in increasing the residual activity and reducing protein
      aggregation. A more thermostable IgG1 did not benefit from cooled nebulization.
      Nebulizer cooling is a prerequisite to retain the activity and stability of
      thermolabile proteins during vibrating mesh nebulization. It is best achieved by
      micro Peltier based active cooling or by simple passive cooling strategies.

PMID- 24662438
TI  - Intracranial hemorrhage during dabigatran treatment.
AB  - BACKGROUND: The incidence of intracranial bleeding during dabigatran treatment is
      lower than that during warfarin treatment. The characteristics of intracranial
      hemorrhage during dabigatran therapy, however, remain unclear. METHODS AND
      RESULTS: The clinical data and treatment summaries of 9 intracranial bleeds that
      developed during dabigatran treatment in 8 patients with non-valvular atrial
      fibrillation were retrospectively reviewed. Five patients had small-moderate
      subdural hematomas, 2 had intracerebral hemorrhage and 1 had traumatic
      subarachnoid and parenchymal hemorrhage associated with cerebral contusion.
      Activated partial thromboplastin time upon admission ranged from 31.6 to 72.4s.
      After admission, systolic blood pressure in the 2 patients with intracerebral
      hemorrhage was maintained below 140 mmHg, and the subdural hematomas in 4
      patients were surgically treated. None of the hematomas became enlarged and
      outcome was good in most cases. CONCLUSIONS: Hematomas that arise due to acute
      intracranial bleeding during dabigatran treatment seem to remain small to
      moderate, hard to expand, and manageable.

PMID- 24662439
TI  - Comparison of body mass index, waist circumference, and waist-to-height ratio for
      predicting the clustering of cardiometabolic risk factors by age in Japanese
      workers--Japan Epidemiology Collaboration on Occupational Health study.
AB  - BACKGROUND: Waist-to-height ratio (WHtR) has been suggested as a better screening
      tool than body mass index (BMI) and waist circumference (WC) for assessing
      cardiometabolic risk. However, most previous studies did not consider age.
      METHODS AND RESULTS: Participants were 45,618 men and 8,092 women aged 15-84
      years who received periodic health checkups in 9 companies in Japan. Clustering
      of cardiometabolic risk factors was defined by the existence of 2 or more of high
      blood pressure, hyperglycemia, and dyslipidemia. In both men and women,
      unadjusted area under the curve (AUC) of the receiver-operating characteristic
      curve for WHtR in detecting the clustering of cardiometabolic risk factors was
      significantly higher than that for either BMI or WC; the AUCs for WHtR, BMI, and
      WC, respectively, were 0.734, 0.705, and 0.717 in men and 0.782, 0.762, and 0.755
      in women. After adjustment for age, however, such differences were not observed;
      the corresponding values were 0.702, 0.701, and 0.696 in men. In women, the age
      adjusted AUC for BMI was slightly higher than for other indices (WHtR, 0.721;
      BMI, 0.726; WC, 0.707). CONCLUSIONS: The screening performance of WHtR for
      detecting the clustering cardiometabolic risk factors was not superior to that of
      BMI.

PMID- 24662440
TI  - Genotyping, evolution and epidemiological findings of Rickettsia species.
AB  - Rickettsiae are obligate intracellular bacteria that can cause mild to life
      threatening diseases, including epidemic typhus, one of the oldest pernicious
      diseases of mankind. Clinical awareness of rickettsial diseases and molecular
      diagnosis have shown that rickettsioses should be viewed as new emerging and
      reemerging diseases. Rickettsia has been shown to be a large genus with a
      worldwide distribution, a very diverse host range, including hosts that have no
      relationship with vertebrate. Genomic studies have demonstrated genome reduction
      due to gene loss associated with increased pathogenicity and horizontal DNA
      acquisition according to a sympatric mode of evolution in hosts that contain
      several organisms. This article presents a review of genotyping techniques and
      examines the principle of genotype determination in terms of taxonomic strategies
      and detection methods. This article summarizes the epidemiological and
      pathological features of Rickettsia and discusses the genomic findings that help
      the understanding of the evolution of pathogenicity including the deleterious
      mutations of repair systems and the toxin-antitoxin systems. 

PMID- 24662441
TI  - Frequency and distribution of simple and compound microsatellites in forty-eight
      Human papillomavirus (HPV) genomes.
AB  - Simple sequence repeats (SSRs) are tandem-repeated sequences ubiquitously present
      but differentially distributed across genomes. Present study is a systematic
      analysis for incidence, composition and complexity of different microsatellites
      in 48 representative Human papillomavirus (HPV) genomes. The analysis revealed a
      total of 1868 SSRs and 120 cSSRs. However, four genomes (HPV-60, HPV-92, HPV-112
      and HPV-136) lacked any cSSR content; while HPV-31 accounted for a maximum of 10
      cSSRs. An overall increase in cSSR% with higher dMAX was observed. The SSRs and
      cSSRs were prevalent in coding regions. Poly(A/T) repeats were significantly more
      abundant than poly(G/C) repeats possibly due to high (A/T) content of the HPV
      genomes. Further, higher prevalence of di-nucleotide repeats over tri-nucleotide
      repeats may be attributed to instability of former because of higher slippage
      rate. An in-depth study of the satellite sequences would provide an insight into
      the imperfections and evolution of microsatellites. 

PMID- 24662442
TI  - Reference values of the right ventricular outflow tract systolic excursion in 711
      healthy children and calculation of z-score values.
AB  - OBJECTIVE: Quantitative determination of right ventricular (RV) function has
      gained more interest over the last years. The RV outflow tract systolic excursion
      (RVOT SE) has been recently proposed as an echocardiographic tool to assess RV
      systolic function in adults. We aimed to determine growth-related changes of RVOT
      SE in children and to establish references values. STUDY DESIGN: A prospective
      study was conducted in a group of 711 healthy paediatric patients (age: 1 day to
      18 years). We determined the effects of age and body surface area (BSA) on RVOT
      SE values. RVOT SE values were further correlated with the established RV
      systolic function parameters tricuspid annular plane systolic excursion (TAPSE)
      and tricuspid annular peak systolic velocity (S'). RESULTS: The RVOT SE ranged
      from a mean of 3.4 mm in neonates to 9.5 mm in 18-year-old adolescents. The RVOT
      SE values showed a positive correlation with age (r = 0.90, P < 0.001) and BSA (r
      = 0.91, P < 0.001). A significant positive correlation was seen between RVOT SE
      and TAPSE (r = 0.93, P < 0.001) and also between RVOT SE and S' (r = 0.86, P <
      0.001) in our patients. CONCLUSION: RVOT SE provides a simple measure and, in
      combination with long-axis excursion parameters TAPSE and S', a comprehensive
      assessment of RV systolic function. Z-scores of RVOT SE values were calculated,
      and percentile charts were established to serve as reference data.

PMID- 24662443
TI  - Serial optical frequency domain imaging in STEMI patients: the follow-up report
      of TROFI study.
AB  - AIMS: To investigate the incidence of incomplete stent apposition and to explore
      the impact of the presence of thrombus and protruding plaque after stent
      implantation on neointima formation at follow-up in ST-segment elevation
      myocardial infarction (STEMI) patients with serial optical frequency domain
      imaging (OFDI) investigations. METHODS AND RESULTS: In a multi-centre study, 141
      patients with ST elevation myocardial infarction <12 h from onset were randomized
      to either PPCI with thrombectomy (TB) using an Eliminate catheter (TB: n = 71) or
      without TB (non-TB: n = 70). OFDI after drug-eluting stenting was performed using
      TERUMO OFDI system. Per protocol, at follow-up 49 patients segments were
      reimaged. At post-procedure and follow-up, there were no differences in stent and
      lumen areas between the two groups. At follow-up, per strut-level analysis,
      percentage of incompletely apposed struts was 0.42 +/- 0.94 vs. 0.38 +/- 0.77% (P
      = 0.76), and percentage of covered struts was 92.7 +/- 7.2 vs. 94.4 +/- 9.2% (P =
      0.47) in the TB and non-TB groups, respectively. There was a positive correlation
      between intra-stent structure (ISS) volume at post-procedure and the neointima
      volume at 6-month follow-up (Pearson's r = 0.409, P = 0.04). Up to 12 months,
      there have been two and four patients having target vessel failure in the TB and
      in the non-TB groups, respectively. CONCLUSIONS: In patients with STEMI, there
      were no significant differences in OFDI parameters between TB and non-TB groups
      at both post-procedure and 6-month follow-up. However, ISS volume at post
      procedure was positively associated with neointimal volume at 6-month follow-up.

PMID- 24662444
TI  - Updated standards and processes for accreditation of echocardiographic
      laboratories from The European Association of Cardiovascular Imaging.
AB  - Standards for echocardiographic laboratories were proposed by the European
      Association of Echocardiography (now the European Association of Cardiovascular
      Imaging) 7 years ago in order to raise standards of practice and improve the
      quality of care. Criteria and requirements were published at that time for
      transthoracic, transoesophageal, and stress echocardiography. This paper
      reassesses and updates the quality standards to take account of experience and
      the technical developments of modern echocardiographic practice. It also
      discusses quality control, the incentives for laboratories to apply for
      accreditation, the reaccreditation criteria, and the current status and future
      prospects of the laboratory accreditation process. 

PMID- 24662445
TI  - Cost-effectiveness of enhancing adherence with oral bisphosphonates treatment in
      osteoporotic women: an empirical approach based on healthcare utilisation
      databases.
AB  - OBJECTIVE: Adherence with bisphosphonates therapy is generally low. Enhancing
      adherence with bisphosphonates would be effective in achieving the full benefits
      of therapy albeit a growth in the expenditure for supporting incremented drug use
      is expected. The cost-effectiveness of enhancing adherence with oral
      bisphosphonates in a large population of osteoporotic women has been assessed in
      the current study. DESIGN: Retrospective cohort study. SETTING: Healthcare
      utilisation databases of Lombardy Region, Italy. PARTICIPANTS: A cohort of 28 558
      women aged 45 years or more, resident in the Italian Region of Lombardy, who were
      newly treated with oral bisphosphonates during 2003-2004, was followed for 6
      years after index prescription. OUTCOME MEASURES: Fracture-free survival time,
      healthcare cost and incremental cost-effectiveness ratio (ICER) of enhancing
      adherence, that is, the additional cost that would be spent every year for
      gaining one fracture-free year as a consequence of enhancing adherence at a
      certain level. RESULTS: Enhanced adherence from 33% (baseline) to 80%, increased
      both fracture-free survivals from 970 to 973 years and healthcare costs from ?118
      000 to ?265 000 every 1000 woman-years, with ICER value of ?53 000 (95% CI ?49
      000 to ?58 000). ICER values were lower for older women (?50 000; 95% CI ?42 000
      to ?58 000) and for those suffering from at least a chronic comorbidity (?25000;
      95% CI 95% CI ?7000 to ?47 000). CONCLUSIONS: Enhancing adherence with oral
      bisphosphonates offers important benefits in reducing the risk of fracture,
      although at a substantial cost.

PMID- 24662446
TI  - Clinical trial participants' experiences of completing questionnaires: a
      qualitative study.
AB  - OBJECTIVES: To improve clinical study developments for elderly populations, we
      aim to understand how they transfer their experiences into validated,
      standardised self-completed study measurement instruments. We analysed how women
      (mean 78+/-8 years of age) participating in a randomised controlled trial (RCT)
      cognised study instruments used to evaluate outcomes of the intervention.
      SETTING: The interview study was nested in an RCT on chronic neck pain using
      common measurement instruments situated in an elderly community in Berlin,
      Germany, which comprised of units for independent and assisted-living options.
      PARTICIPANTS: The sample (n=20 women) was selected from the RCT sample (n=117,
      95% women, mean age 76 (SD+/-8) years). Interview participants were selected
      using a purposive sampling list based on the RCT outcomes. OUTCOMES: We asked
      participants about their experiences completing the RCT questionnaires.
      Interviews were analysed thematically, then compared with the questionnaires.
      RESULTS: Interviewees had difficulties in translating complex experiences into a
      single value on a scale and understanding the relationship of the questionnaires
      to study aims. Interviewees considered important for the trial that their actual
      experiences were understood by trial organisers. This information was not
      transferrable by means of the questionnaires. To rectify these difficulties,
      interviewees used strategies such as adding notes, adding response categories or
      skipping an item. CONCLUSIONS: Elderly interview participants understood the
      importance of completing questionnaires for trial success. This led to strategies
      of completing the questionnaires that resulted in 'missing' or ambiguous data. To
      improve data collection in elderly populations, educational materials addressing
      the differential logics should be developed and tested. Pilot testing validated
      instruments using cognitive interviews may be particularly important in such
      populations. Finally, when the target of an intervention is a subjective
      experience, it seems important to create a method by which participants can
      convey their personal experiences. These could be nested qualitative studies.
      TRIAL REGISTRATION NUMBER: ISRCTN77108101807.

PMID- 24662447
TI  - Association of digital vascular function with cardiovascular risk factors: a
      population study.
AB  - OBJECTIVES: Vasodilation of the peripheral arteries during reactive hyperaemia
      depends in part on release of nitric oxide from endothelial cells. Previous
      studies mainly employed a fingertip tonometric device to derive pulse wave
      amplitude (PWA) and PWA hyperaemic changes. An alternative approach is based on
      photoplethysmography (PPG). We sought to evaluate the correlates of digital PPG
      PWA hyperaemic responses as a measure of peripheral vascular function. DESIGN:
      The Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO) is a
      population-based cohort study. SETTING: Respondents were examined at one centre
      in northern Belgium. PARTICIPANTS: For this analysis, our sample consisted of 311
      former participants (53.5% women; mean age 52.6 years; 43.1% hypertensive), who
      were examined from January 2010 until March 2012 (response rate 85.1%). PRIMARY
      OUTCOME MEASURES: Using a fingertip PPG device, we measured digital PWA at
      baseline and at 30 s intervals for 4 min during reactive hyperaemia induced by a
      5 min forearm cuff occlusion. We performed stepwise regression to identify
      correlates of the hyperaemic response ratio for each 30 s interval after cuff
      deflation. RESULTS: The maximal hyperaemic response was detected in the 30-60 s
      interval. The explained variance for the PPG PWA ratio ranged from 9.7% at 0-30 s
      interval to 22.5% at 60-90 s time interval. The hyperaemic response at each 30 s
      interval was significantly higher in women compared with men (p<=0.001). The PPG
      PWA changes at 0-90 s intervals decreased with current smoking (p<=0.0007) and at
      0-240 s intervals decreased with higher body mass index (p<=0.035). These
      associations with sex, current smoking and body mass index were mutually
      independent. CONCLUSIONS: Our study is the first to implement the new PPG
      technique to measure digital PWA hyperaemic changes in a general population.
      Hyperaemic response, as measured by PPG, is inversely associated with traditional
      cardiovascular risk factors such as male sex, smoking and obesity.

PMID- 24662448
TI  - Diagnostic accuracy of copeptin sensitivity and specificity in patients with
      suspected non-ST-elevation myocardial infarction with troponin I below the 99th
      centile at presentation.
AB  - OBJECTIVE: To determine whether copeptin-us can rule out diagnosis of non-ST
      segment elevation myocardial infarction (NSTEMI) without prolonged monitoring and
      serial blood sampling in patients with high-sensitive cardiac troponin I (hs
      cTnI) below the 99th centile at presentation to the emergency department (ED)
      [corrected]. DESIGN: Prospective, non-randomised, individual blinded diagnostic
      accuracy study. SETTING: Two EDs of a rural region of France. PARTICIPANTS:
      Patients with chest pain suspected of NSTEMI with onset within the last 12 h were
      considered for enrollment. INTERVENTIONS: Serial clinical, electrographical and
      biochemical investigations were performed at admission and after 2, 4, 6 and 12
      h. Hs-cTnI was measured using an assay with Dimension VISTA, Siemens [corrected].
      Copeptin was measured by the BRAHMS copeptin-us assay on the KRYPTOR Compact Plus
      system. The follow-up period was 90 days. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Copeptin, troponin, myoglobin and creatine kinase values. Clinical and
      paraclinical events. The final diagnosis was adjudicated blinded to copeptin
      result. RESULTS: During 12 months, 102 patients were analysed. Final diagnosis
      was NSTEMI for 7.8% (n=8), unstable angina for 3.9% (n=4), cardiac but non
      coronary artery disease for 8.8% (n=9), non-cardiac chest pain for 52% (n=53) and
      unknown for 27.5% (n=28). There was no statistical difference for copeptin values
      between patients with NSTEMI and others (respectively 5.5 pmol/L IQR (3.1-7.9)
      and 6.5 pmol/L IQR (3.9-12.1), p=0.49). Only one patient with NSTEMI had a
      copeptin value above the cut-off of 95th centile at admission. CONCLUSIONS: In
      this study, copeptin does not add a diagnostic value at admission to ED for
      patients with suspected acute coronary syndrome without ST-segment elevation and
      with hs-cTnI below the 99th centile [corrected]. TRIAL REGISTRATION NUMBER:
      Clinicaltrials.gov identifier: NCT01334645.

PMID- 24662449
TI  - Adapting data collection methods in the Australian Life Histories and Health
      Survey: a retrospective life course study.
AB  - OBJECTIVE: Ideally, life course data are collected prospectively through an
      ongoing longitudinal study. We report adaptive multimethod fieldwork procedures
      that gathered life history data by mail survey and telephone interview,
      comparable with the face-to-face methods employed in the English Longitudinal
      Study on Ageing (ELSA). DESIGN: The Australian Life Histories and Health (LHH)
      Survey was a substudy of the Australian 45 and Up Study, with data collection
      methods modified from the ELSA Study. A self-complete questionnaire and life
      history calendar were completed by the participants, followed by a computer
      assisted telephone interview recording key life events. RESULTS: The LHH survey
      developed and tested procedures and instruments that gathered rich life history
      data within an ongoing Australian longitudinal survey on ageing. Data collection
      proved to be economical. The use of a self-complete questionnaire in conjunction
      with a life history calendar and coordinated computer-assisted telephone
      interview was successful in collecting retrospective life course information, in
      terms of being thorough, practical and efficient. This study has a diverse
      collection of data covering the life course, starting with early life experiences
      and continuing with socioeconomic and health exposures and outcomes during adult
      life. CONCLUSIONS: Mail and telephone methodology can accurately and economically
      add a life history dimension to an ongoing longitudinal survey. The method is
      particularly valuable for surveying widely dispersed populations. The results
      will facilitate understanding of the social determinants of health by gathering
      data on earlier life exposures as well as comparative data across geographical
      and societal contexts.

PMID- 24662450
TI  - An interactive tool for outdoor computer controlled cultivation of microalgae in
      a tubular photobioreactor system.
AB  - This paper describes an interactive virtual laboratory for experimenting with an
      outdoor tubular photobioreactor (henceforth PBR for short). This virtual
      laboratory it makes possible to: (a) accurately reproduce the structure of a real
      plant (the PBR designed and built by the Department of Chemical Engineering of
      the University of Almeria, Spain); (b) simulate a generic tubular PBR by changing
      the PBR geometry; (c) simulate the effects of changing different operating
      parameters such as the conditions of the culture (pH, biomass concentration,
      dissolved O2, inyected CO2, etc.); (d) simulate the PBR in its environmental
      context; it is possible to change the geographic location of the system or the
      solar irradiation profile; (e) apply different control strategies to adjust
      different variables such as the CO2 injection, culture circulation rate or
      culture temperature in order to maximize the biomass production; (f) simulate the
      harvesting. In this way, users can learn in an intuitive way how productivity is
      affected by any change in the design. It facilitates the learning of how to
      manipulate essential variables for microalgae growth to design an optimal PBR.
      The simulator has been developed with Easy Java Simulations, a freeware open
      source tool developed in Java, specifically designed for the creation of
      interactive dynamic simulations. 

PMID- 24662451
TI  - Electrical characterization of photodetectors based on poly(3-hexylthiophene-2,5
      diyl) layers.
AB  - This paper presents the electrical characteristics of solution-processed organic
      photodetectors based on poly(3-hexylthiophene-2,5-diyl) semiconducting polymer
      layers deposited by spin-coating on interdigitated metal electrodes. Four
      different electrode shapes have been used for this study in order to appraise the
      optimum electrode geometry. The measurement of the resistance as a function of
      the temperature reveals a transition from negative to positive temperature
      coefficient material around 80  degrees C for the polymer layers. Besides, slow
      reversible changes in the photodetectors conductivity were observed when moved
      from vacuum to the air and under illumination with a xenon lamp, which can be
      explained by the formation of charge transfer complexes with molecular oxygen and
      the polymer. The photogenerated current-light power ratio was found to be
      approximately linear in the 200 to 550 mW/cm2 range. 

PMID- 24662452
TI  - Influence of surface position along the working range of conoscopic holography
      sensors on dimensional verification of AISI 316 wire EDM machined surfaces.
AB  - Conoscopic holography (CH) is a non-contact interferometric technique used for
      surface digitization which presents several advantages over other optical
      techniques such as laser triangulation. Among others, the ability for the
      reconstruction of high-sloped surfaces stands out, and so does its lower
      dependence on surface optical properties. Nevertheless, similarly to other
      optical systems, adjustment of CH sensors requires an adequate selection of
      configuration parameters for ensuring a high quality surface digitizing. This
      should be done on a surface located as close as possible to the stand-off
      distance by tuning frequency (F) and power (P) until the quality indicators
      Signal-to-Noise Ratio (SNR) and signal envelope (Total) meet proper values.
      However, not all the points of an actual surface are located at the stand-off
      distance, but they could be located throughout the whole working range (WR).
      Thus, the quality of a digitized surface may not be uniform. The present work
      analyses how the quality of a reconstructed surface is affected by its relative
      position within the WR under different combinations of the parameters F and P.
      Experiments have been conducted on AISI 316 wire EDM machined flat surfaces. The
      number of high-quality points digitized as well as distance measurements between
      different surfaces throughout the WR allowed for comparing the metrological
      behaviour of the CH sensor with respect to a touch probe (TP) on a CMM. 

PMID- 24662453
TI  - Towards a holistic framework for the evaluation of emergency plans in indoor
      environments.
AB  - One of the most promising fields for ambient intelligence is the implementation
      of intelligent emergency plans. Because the use of drills and living labs cannot
      reproduce social behaviors, such as panic attacks, that strongly affect these
      plans, the use of agent-based social simulation provides an approach to evaluate
      these plans more thoroughly. (1) The hypothesis presented in this paper is that
      there has been little interest in describing the key modules that these
      simulators must include, such as formally represented knowledge and a realistic
      simulated sensor model, and especially in providing researchers with tools to
      reuse, extend and interconnect modules from different works. This lack of
      interest hinders researchers from achieving a holistic framework for evaluating
      emergency plans and forces them to reconsider and to implement the same
      components from scratch over and over. In addition to supporting this hypothesis
      by considering over 150 simulators, this paper: (2) defines the main modules
      identified and proposes the use of semantic web technologies as a cornerstone for
      the aforementioned holistic framework; (3) provides a basic methodology to
      achieve the framework; (4) identifies the main challenges; and (5) presents an
      open and free software tool to hint at the potential of such a holistic view of
      emergency plan evaluation in indoor environments. 

PMID- 24662454
TI  - Relationship between EGFR expression, EGFR mutation status, and the efficacy of
      chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell
      lung cancer.
AB  - INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell
      lung cancer indicated that the survival benefit associated with the addition of
      cetuximab to cisplatin and vinorelbine was limited to patients whose tumors
      expressed high levels of epidermal growth factor receptor (EGFR)
      (immunohistochemistry score of >=200; scale 0-300). We assessed whether the
      treatment effect was also modulated in FLEX study patients by tumor EGFR mutation
      status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of
      1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression
      groups was analyzed across efficacy endpoints according to tumor EGFR mutation
      status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971
      tumors (14%), 970 of which were also evaluable for EGFR expression level. The
      most common mutations were exon 19 deletions and L858R (124 of 133 patients;
      93%). In the high EGFR expression group (immunohistochemistry score of >=200), a
      survival benefit for the addition of cetuximab to chemotherapy was demonstrated
      in patients with EGFR wild-type (including T790M mutant) tumors. Although patient
      numbers were small, those in the high EGFR expression group whose tumors carried
      EGFR mutations may also have derived a survival benefit from the addition of
      cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the
      high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The
      survival benefit associated with the addition of cetuximab to first-line
      chemotherapy for advanced non-small-cell lung cancer expressing high levels of
      EGFR is not limited by EGFR mutation status.

PMID- 24662456
TI  - Correlation of regional emphysema and lung cancer: a lung tissue research
      consortium-based study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease and lung cancer are linked
      because both airflow obstruction and emphysema, on computer tomography, are
      independent risk factors for lung cancer. However, the local risk of malignancy
      relative to development of regional emphysema has not yet been defined.
      Specifically, it is not known if primary lung cancers are associated with regions
      of worse emphysema within individual patients. METHODS: We performed a database
      analysis evaluating the association between the degree of regional emphysema as
      scored on computer tomography and development of primary lung cancer. We also
      studied the association between regional emphysema and benign lung nodules. We
      assembled two distinct cohorts using the National Heart, Lung, and Blood
      Institute's Lung Tissue Research Consortium database, hypothesizing that lung
      malignancy will preferentially locate in the regions of the most severe
      emphysema. RESULTS: In the Lung Tissue Research Consortium database, 624 cases
      met criteria for the malignant nodule cohort and 64 were included in the benign
      nodule cohort. When comparing location of a malignant nodule to other lung
      regions within the same person, the odds of having a more severe emphysema score
      in the location of lung cancer was 1.342 (95% confidence interval 1.112-1.620; p
      = 0.0022). When comparing location of a benign nodule to other lung regions
      within the same person, the odds of having a more severe emphysema score in the
      location of the benign nodule was 1.118 (95% confidence interval 0.725-1.725; p =
      0.6137). CONCLUSIONS: Primary lung cancers are associated with areas of worse
      regional emphysema.

PMID- 24662455
TI  - Membrane carbonic anhydrase IX expression and relapse risk in resected stage I-II
      non-small-cell lung cancer.
AB  - BACKGROUND: Adjuvant chemotherapy reduces recurrences of non-small-cell lung
      cancer (NSCLC). To determine which patients need adjuvant chemotherapy, we
      assessed factors associated with time to relapse (TTR). METHODS: In 230 resected
      stage I-II NSCLCs, we correlated immunohistochemistry scores for factors
      associated with cell growth rate, growth regulation, hypoxia, cell survival, and
      cell death with TTR. RESULTS: With a median follow-up of 82 months (1-158) for
      those alive and relapse free at last follow-up, median time to recurrence was not
      reached. The 2- and 5-year probabilities of maintaining freedom from recurrence
      were 80.7% (95% confidence interval, 75.3%, 86.4%) and 74.6% (95% confidence
      interval, 68.6%, 81.2%), respectively. TTR curves flattened at an apparent cure
      rate of 70%. In multicovariate Cox models, factors correlating with shorter TTR
      were membranous carbonic anhydrase IX (mCAIX) staining (any versus none, hazard
      ratio = 2.083, p = 0.023) and node stage (N1 versus N0, hazard ratio = 2.591, p =
      0.002). mCAIX scores correlated positively with tumor size, grade, squamous
      histology, necrosis, mitoses, Ki67, p53, nuclear DNA methyltransferase 1, and
      cytoplasmic enhancer-of-split-and-hairy-related protein, and they correlated
      inversely with papillary histology, epidermal growth factor receptor mutation
      (trend), copper transporter-1, and cytoplasmic hypoxia-inducible factor-1alpha,
      vascular endothelial growth factor, DNA methyltransferase 1, and excision repair
      cross-complementing rodent repair deficiency, complementation group 1.
      CONCLUSION: Nodal stage and mCAIX immunohistochemistry were the strongest
      independent predictors of shorter TTR in resected NSCLCs. mCAIX correlated with
      tumor size, markers of tumor proliferation and necrosis, and tumor genetic
      characteristics, and it paradoxically correlated inversely with the hypoxia
      markers, hypoxia-inducible factor-1alpha and vascular endothelial growth factor.
      Presence of mCAIX could help determine patients with high risk of recurrence who
      might require adjuvant chemotherapy.

PMID- 24662457
TI  - Lung cancer-associated myofibroblasts reveal distinctive ultrastructure and
      function.
AB  - BACKGROUND: Cancer-associated stromal cells interact with carcinoma cells and
      thus participate in tumor growth. Our aim was to characterize the ultrastructure
      and contractile properties of stromal cells in collagen gel cultured from lung
      cancer of various histological types and from tumor-free lung. METHODS: Cells
      cultured from lung cancer (13 adenocarcinomas, six squamous cell carcinomas, one
      adenosquamous carcinoma, and one pleomorphic carcinoma) and tumor-free lung were
      analyzed by transmission electron microscopy and three-dimensional collagen gel
      contraction assays. The expression of alpha-smooth muscle actin (alpha-SMA), a
      recognized myofibroblast marker, was examined by immunoelectron microscopy from
      individual cells and by Western blotting from the whole cultured cell population.
      RESULTS: According to their ultrastructure, the cell lines were composed of
      fibroblastic and myofibroblastic cells. In electron microscopy, cells of lung
      cancer exhibited more myofibroblastic features displaying higher amounts of actin
      belts (p = 0.057) and alpha-SMA labeling (p = 0.010) than cells from tumor-free
      lung. Myofibroblasts cultured from lung cancer of smokers expressed less alpha
      SMA labeling (p = 0.013) than counterparts from nonsmokers. Western blotting
      revealed that cancer-associated fibroblasts expressed more alpha-SMA (p = 0.006)
      than cells from tumor-free lung, whereas cells from tumor-free central lung of
      smokers showed less alpha-SMA (p = 0.039) than counterparts from nonsmokers.
      Cells cultured from cancer contracted more in collagen gel than those from tumor
      free lung. The contractile capacity in collagen gel correlated with the frequency
      of extracellular component of fibronexus by transmission electron microscopy.
      CONCLUSIONS: Lung cancer-associated myofibroblasts are different both
      ultrastructurally and functionally when compared with cells cultured from tumor
      free lung. Smoking altered myofibroblastic phenotype, regardless of their origin.

PMID- 24662459
TI  - miR-137 controls proliferation and differentiation of human adipose tissue
      stromal cells.
AB  - BACKGROUND/AIMS: Demonstrating the molecular mechanisms of human adipose tissue
      derived mesenchymal stem cells (hADSCs) differentiation and proliferation could
      develop hADSCs-based cell therapy. METHODS: The microRNA-137 (miR-137) and cell
      division control protein 42 homolog (CDC42) levels were regulated by
      oligonucleotides transfection. The adipogenic differentiation was induced for 10
      days in an adipogenic medium and assessed by using an Oil Red O stain. The
      regulation of miR-137 on CDC42 expression was determined by western blot, real
      time PCR and luciferase reporter assay. RESULTS: We confirmed the roles of miR
      137 on hADSCs proliferation and adipogenic differentiation. We showed that
      overexpression of miR-137 inhibited both hADSCs proliferation and adipogenic
      differentiation. Overexpression of miR-137 also downregulated protein and mRNA
      levels of CDC42, a predicted target of miR-137. In contrast, inhibition of miR
      137 with 2'-O-methyl antisense RNA increased proliferation and adipogenic
      differentiation in hADSCs. Luciferase reporter activity in the miR-137 target
      site within the CDC42 3'UTR was lower in miR-137-transfected hADSCs than in
      control miRNA-transfected hADSCs. RNA interference-mediated downregulation of
      CDC42 in hADSCs inhibited their proliferation and adipogenic differentiation.
      CONCLUSION: Our results indicate that miR-137 regulates hADSCs adipogenic
      differentiation and proliferation by directly targeting CDC42. These findings
      improve our knowledge of the molecular mechanisms governing hADSCs
      differentiation and proliferation.

PMID- 24662458
TI  - Cisplatin versus carboplatin-based regimens for the treatment of patients with
      metastatic lung cancer. An analysis of Veterans Health Administration data.
AB  - BACKGROUND: While platinum-based doublet chemotherapy is standard of care for
      patients presenting with metastatic non-small-cell lung cancer, the optimal
      platinum agent (cisplatin versus carboplatin) is unclear. We therefore compared
      survival and toxicity among persons receiving these agents at Department of
      Veterans Affairs hospitals. METHODS: We used the Veterans Affairs Central Cancer
      Registry to identify veterans presented between 2001 and 2008 with metastatic non
      small-cell lung cancer, then selected those receiving initial platinum doublet
      chemotherapy. We compared survival between those receiving cisplatin and
      carboplatin using multivariable Cox proportional hazards models and propensity
      score analyses to adjust for imbalances in demographics and clinical
      characteristics. RESULTS: We identified 4352 eligible persons; 4061 (93%)
      received carboplatin. Patients treated with cisplatin were younger (median age 61
      versus 63, p < 0.01) and had less comorbidities (summary comorbidity score > 2,
      7.7% versus 12.8%, p = 0.01) and higher eGFR (87 versus 84 mL/min/1.73 m). Median
      survival was similar for persons receiving cisplatin and carboplatin (8.1 versus
      7.5 months, p = 0.54). In an adjusted survival analyses, the use of cisplatin was
      not associated with a better survival (hazard ratio 0.98, 95% confidence interval
      0.84-1.14, p = 0.79). We performed subgroup analysis defined by histology and
      second agent, the hazard ratio for mortality ranged spanned 1 and none of these
      approached statistical significance (all p values > 0.20). Cisplatin-treated
      patients were more likely to have more hospitalization (1.7 versus 1.3, p < 0.01)
      and outpatient visits (11 versus 9.6, p < 0.01). Cisplatin-treated patient had
      more subsequent encounters for infection (41.6% versus 34.3%, p < 0.01) and acute
      kidney injury/dehydration (29.2% versus 15.5%, p < 0.01) CONCLUSIONS:: Patients
      receiving cisplatin and carboplatin-based doublets did not have significantly
      different survival, but cisplatin use was associated with an increase morbidity
      and healthcare use.

PMID- 24662460
TI  - Plant GSK3 proteins regulate xylem cell differentiation downstream of TDIF-TDR
      signalling.
AB  - During plant radial growth typically seen in trees, procambial and cambial cells
      act as meristematic cells in the vascular system to self-proliferate and
      differentiate into xylem cells. These two processes are regulated by a signalling
      pathway composed of a peptide ligand and its receptor; tracheary element
      differentiation inhibitory factor (TDIF) and TDIF RECEPTOR (TDR). Here we show
      that glycogen synthase kinase 3 proteins (GSK3s) are crucial downstream
      components of the TDIF signalling pathway suppressing xylem differentiation from
      procambial cells. TDR interacts with GSK3s at the plasma membrane and activates
      GSK3s in a TDIF-dependent fashion. Consistently, a specific inhibitor of plant
      GSK3s strongly induces xylem cell differentiation through BRI1-EMS SUPPRESSOR 1
      (BES1), a well-known target transcription factor of GSK3s. Our findings provide
      insight into the regulation of cell fate determination in meristem maintenance. 

PMID- 24662461
TI  - Transcatheter treatment of chronic mitral regurgitation with the MitraClip
      system: an Italian consensus statement.
AB  - New percutaneous technologies are rapidly emerging for the treatment of
      structural heart disease including mitral valve disease. Preliminary data suggest
      a potential clinical benefit of percutaneous treatment of mitral regurgitation by
      the MitraClip procedure in selected patients. Until final data are available from
      randomized, controlled, multicenter clinical trials, there is an urgent need for
      a consensus among all the operators involved in the treatment of patients with
      mitral regurgitation, including clinical cardiologists, heart failure
      specialists, surgeons, interventional cardiologists, and imaging experts. In the
      absence of evidence-based guidelines, the heart-team approach is the most
      reliable method of making proper decisions. This study is the result of
      multidisciplinary consensus activity, and has the aim of helping physicians in
      the difficult task of making decisions for the treatment of patients with mitral
      regurgitation. It is the result of a joint effort of the major Italian Cardiology
      and Cardiac Surgery Societies, working together to find a proper balance between
      the points of view of the clinical cardiologist, the interventional cardiologist,
      and the cardiac surgeon. 

PMID- 24662462
TI  - Morphology-dependent bactericidal activities of Ag/CeO2 catalysts against
      Escherichia coli.
AB  - Silver-loaded CeO2 nanomaterials (Ag/CeO2) including Ag/CeO2 nanorods, nanocubes,
      nanoparticles were prepared with hydrothermal and impregnation methods. Catalytic
      inactivation of Escherichia coli with Ag/CeO2 catalysts through the formation of
      reactive oxygen species (ROS) was investigated. For comparison purposes, the
      bactericidal activities of CeO2 nanorods, nanocubes and nanoparticles were also
      studied. There was a 3-4 log order improvement in the inactivation of E. coli
      with Ag/CeO2 catalysts compared with CeO2 catalysts. Temperature-programmed
      reduction of H2 showed that Ag/CeO2 catalysts had higher catalytic oxidation
      ability than CeO2 catalysts, which was the reason for that Ag/CeO2 catalysts
      exhibited stronger bactericidal activities than CeO2 catalysts. Further, the
      bactericidal activities of CeO2 and Ag/CeO2 depend on their shapes. Results of
      5,5-dimethyl-1-pyrroline-N-oxide spin-trapping measurements by electron spin
      resonance and addition of catalase as a scavenger indicated the formation of OH,
      O2(-), and H2O2, which caused the obvious bactericidal activity of catalysts. The
      stronger chemical bond between Ag and CeO2 nanorods led to lower Ag(+) elution
      concentrations. The toxicity of Ag(+) eluted from the catalysts did not play an
      important role during the bactericidal process. Experimental results also
      indicated that Ag/CeO2 induced the production of intracellular ROS and disruption
      of the cell wall and cell membrane. A possible production mechanism of ROS and
      bactericidal mechanism of catalytic oxidation were proposed. 

PMID- 24662463
TI  - Antibacterial properties of water-soluble gold(I) N-heterocyclic carbene
      complexes.
AB  - The antibacterial properties of water-soluble gold(I) complexes [1-methyl-3-(3
      sulfonatopropyl)imidazol-2-ylidene]gold(I) chloride (C1), [1-mesityl-3-(3
      sulfonatopropyl)imidazol-2-ylidene]gold(I) chloride (C2), [1-(2,6
      diisopropylphenyl)-3-(3-sulfonatopropyl)imidazol-2-ylidene]gold(I) chloride (C3)
      and [1,3-bis(2,6-diisopropyl-4-sodiumsulfonatophenyl)imidazol-2-ylidene]gold(I)
      chloride (C4) and the respective ligands were assessed by agar diffusion and
      broth macrodilution methods against Gram-positives Staphylococcus aureus,
      Enterococcus faecalis and Micrococcus luteus and the Gram-negative bacteria
      Yersinia ruckeri, Pseudomonas aeruginosa and Escherichia coli. Viability after
      treatments was determined by direct plate count. The bactericidal activity
      displayed by C1 and C3 was comparable to that of AgNO3. 

PMID- 24662464
TI  - Nitrate as a probe of cytochrome c surface: crystallographic identification of
      crucial "hot spots" for protein-protein recognition.
AB  - The electrostatic surface of cytochrome c and its changes with the iron oxidation
      state are involved in the docking and undocking processes of this protein to its
      biological partners in the mitochondrial respiratory pathway. To investigate the
      subtle mechanisms of formation of productive macromolecular complexes and of
      their breakage following the electron transfer process, the X-ray structures of
      horse heart ferri-cytochrome c (trigonal form) and ferro-cytochrome c (monoclinic
      form) were obtained using nitrate ions both as a crystallizing agent and an
      anionic probe for mapping the electrostatic surface changes. Both crystal forms
      contain three protein molecules in the asymmetric unit. In addition, a total of
      21.5 and 18 crystallographically independent nitrate ions were identified for the
      trigonal and monoclinic forms, respectively. By matching all the six
      crystallographically independent protein molecules, 26 different anion-protein
      interaction sites were identified on the surfaces of cytochrome c, 10 of which
      were found in both forms, 8 present only in the oxidized and 8 only in the
      reduced form. The structural analysis of the electron transfer complexes, based
      on this new information, suggests a specific exit strategy for cytochrome c after
      formation of productive protein-protein complexes: a directional sliding
      mechanism for the electron shuttle on the surface of the redox partner is
      proposed to take place after the electron transfer process has occurred. 

PMID- 24662465
TI  - Synthesis, physico-chemical properties and biological analysis of newly obtained
      copper(II) complexes with pyrazole derivatives.
AB  - Three new copper(II) complexes containing two different pyrazole bound ligands
      (1, 2) have been synthesized and characterized by IR, LSI-MS (liquid secondary
      ion mass spectrometry) and elemental analysis. (1)H NMR spectra of the organic
      ligands have been recorded. We describe the influence of these complexes on
      particular cancer cell lines and DNA structure by MTT-assay [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], APA (acid phosphatase
      activity)-assay or CD-spectroscopy and agarose gel electrophoresis methods,
      together with their physico-chemical properties such as lipophilicity and
      stability in aqueous solution. The cytotoxic effect on HUVEC (endothelial cells)
      for the most active complex 4 has been also investigated. Moreover, the ability
      of these complexes to induce apoptosis in cancer cells has been assessed by using
      fluorescence microscopy. Our results indicate that dichloridobis{1
      [amino(thioxo)methyl]-5-hydroxy-3-phenyl-1H-pyrazole-kappaN2}copper(II) is the
      most potent complex among the tested complexes. 

PMID- 24662466
TI  - Extended hypoxia in the alfalfa leafcutting bee, Megachile rotundata, increases
      survival but causes sub-lethal effects.
AB  - Many insects are tolerant of hypoxic conditions, but survival may come at a cost
      to long-term health. The alfalfa leaf-cutting bee, Megachile rotundata, develops
      in brood cells inside natural cavities, and may be exposed to hypoxic conditions
      for extended periods of time. Whether M. rotundata is tolerant of hypoxia, and
      whether exposure results in sub-lethal effects, has never been investigated.
      Overwintering M. rotundata prepupae were exposed to 10%, 13%, 17%, 21% and 24% O2
      for 11 months. Once adults emerged, five indicators of quality - emergence
      weight, body size, feeding activity, flight performance, and adult longevity, -
      were measured to determine whether adult bees that survived past exposure to
      hypoxia were competent pollinators. M. rotundata prepupae are tolerant of hypoxic
      condition and have higher survival rates in hypoxia, than in normoxia. Under
      hypoxia, adult emergence rates did not decrease over the 11 months of the
      experiment. In contrast, bees reared in normoxia had decreased emergence rates by
      8 months, and were dead by 11 months. M. rotundata prepupae exposed to extended
      hypoxic conditions had similar emergence weight, head width, and cross-thorax
      distance compared to bees reared in standard 21% oxygen. Despite no significant
      morphological differences, hypoxia-exposed bees had lower feeding rates and
      shorter adult lifespans. Hypoxia may play a role in post-diapause physiology of
      M. rotundata, with prepupae showing better survival under hypoxic conditions.
      Extended exposure to hypoxia, while not fatal, causes sub-lethal effects in
      feeding rates and longevity in the adults, indicating that hypoxia tolerance
      comes at a cost.

PMID- 24662467
TI  - Functional analysis of an immune gene of Spodoptera littoralis by RNAi.
AB  - Insect immune defences rely on cellular and humoral responses targeting both
      microbial pathogens and metazoan parasites. Accumulating evidence indicates
      functional cross-talk between these two branches of insect immunity, but the
      underlying molecular mechanisms are still largely unknown. We recently described,
      in the tobacco budworm Heliothis virescens, the presence of amyloid fibers
      associated with melanogenesis in immune capsules formed by hemocytes, and
      identified a protein (P102) involved in their assembly. Non-self objects coated
      by antibodies directed against this protein escaped hemocyte encapsulation,
      suggesting that P102 might coordinate humoral and cellular defence responses at
      the surface of foreign invaders. Here we report the identification of a cDNA
      coding for a protein highly similar to P102 in a related Lepidoptera species,
      Spodoptera littoralis. Its transcript was abundant in the hemocytes and the
      protein accumulated in large cytoplasmic compartments, closely resembling the
      localization pattern of P102 in H. virescens. RNAi-mediated gene silencing
      provided direct evidence for the role played by this protein in the immune
      response. Oral delivery of dsRNA molecules directed against the gene strongly
      suppressed the encapsulation and melanization response, while hemocoelic
      injections did not result in evident phenotypic alterations. Shortly after their
      administration, dsRNA molecules were found in midgut cells, en route to the
      hemocytes where the target gene was significantly down-regulated. Taken together,
      our data demonstrate that P102 is a functionally conserved protein with a key
      role in insect immunity. Moreover, the ability to target this gene by dsRNA oral
      delivery may be exploited to develop novel technologies of pest control, based on
      immunosuppression as a strategy for enhancing the impact of natural antagonists. 

PMID- 24662468
TI  - Defense strategies used by two sympatric vineyard moth pests.
AB  - Natural enemies including parasitoids are the major biological cause of mortality
      among phytophagous insects. In response to parasitism, these insects have evolved
      a set of defenses to protect themselves, including behavioral, morphological,
      physiological and immunological barriers. According to life history theory,
      resources are partitioned to various functions including defense, implying trade
      offs among defense mechanisms. In this study we characterized the relative
      investment in behavioral, physical and immunological defense systems in two
      sympatric species of Tortricidae (Eupoecilia ambiguella, Lobesia botrana) which
      are important grapevine moth pests. We also estimated the parasitism by
      parasitoids in natural populations of both species, to infer the relative success
      of the investment strategies used by each moth. We demonstrated that larvae
      invest differently in defense systems according to the species. Relative to L.
      botrana, E. ambiguella larvae invested more into morphological defenses and less
      into behavioral defenses, and exhibited lower basal levels of immune defense but
      strongly responded to immune challenge. L. botrana larvae in a natural population
      were more heavily parasitized by various parasitoid species than E. ambiguella,
      suggesting that the efficacy of defense strategies against parasitoids is not
      equal among species. These results have implications for understanding of
      regulation in communities, and in the development of biological control
      strategies for these two grapevine pests. 

PMID- 24662469
TI  - In silico investigation of medicinal spectrum of imidazo-azines from the
      perspective of multitarget screening against malaria, tuberculosis and Chagas
      disease.
AB  - A chemical database of 30 representative imidazo-azines was built and screened
      against important tropical disease targets by computational docking. After three
      rounds of screening, an interaction profile was generated and analyzed. On the
      basis of binding energy and ligand efficiency, it was concluded that in general,
      imidazo-azine scaffold has a potential of being selective and simultaneous
      inhibitor against the five receptors Pf-dihydrofolate reductase, Pf-enoyl acyl
      carrier protein reductase, Pf-protein kinase 7, Mt-pantothenate synthetase and Mt
      thymidine monophosphate kinase. Interestingly, two compounds 2-(4-chlorophenyl)-N
      cyclohexyl-6-methylH-imidazo[1,2-a]pyridine-3-amine (MCL011) and N-cyclohexyl-2
      (4-methoxyphenyl)-6-methylH-imidazo[1,2-a]pyridine-3-amine (MCL017) showed
      highest binding energy against four targets namely Pf-dihydrofolate reductase, Pf
      enoyl acyl carrier protein reductase, Pf-protein kinase 7 and Mt-pantothenate
      synthetase. Eventually, in order to improve the decision making and success rate
      in actual efficacy evaluations other criteria such as lead-likeness were
      envisaged.

PMID- 24662470
TI  - Two-year outcome of patients after a first hospitalization for heart failure: A
      national observational study.
AB  - BACKGROUND: National population-based management and outcome data for patients of
      all ages hospitalized for heart failure have rarely been reported. AIM: National
      population-based management and outcome of patients of all ages hospitalized for
      heart failure have rarely been reported. The present study reports these results,
      based on 77% of the French population, for patients hospitalized for the first
      time for heart failure in 2009. METHODS: The study population comprised French
      national health insurance general scheme beneficiaries hospitalized in 2009 with
      a principal diagnosis of heart failure, after exclusion of those hospitalized for
      heart failure between 2006 and 2008 or with a chronic disease status for heart
      failure. Data were collected from the national health insurance information
      system (SNIIRAM). RESULTS: A total of 69,958 patients (mean age, 78 years; 48%
      men) were studied. The hospital mortality rate was 6.4%, with 1-month, 1-year and
      2-year survival rates of 89%, 71% and 60%, respectively. Heart failure and all
      cause readmission-free rates were 55% and 43% at 1 year and 27% and 17% at 2
      years, respectively. Compared with a reference sample of 600,000 subjects, the
      age- and sex-standardized relative risk of death was 29 (95% confidence interval
      [CI] 28-29) at 2 years, 82 (95% CI 72-94) in subjects aged<50 years and 3 (95% CI
      3-3) in subjects aged >= 90 years. For subjects aged < 70 years who survived 1
      month after discharge, factors associated with a reduction in the 2-year
      mortality rate were: female sex; age < 55 years; absence of co-morbidities; and
      use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,
      beta-blockers, lipid-lowering agents or oral anticoagulants during the month
      following discharge. Poor prognostic factors were treatment with a loop diuretic
      before or after hospitalization and readmission for heart failure within 1 month
      after discharge. CONCLUSIONS: This large population-based study confirms the
      severe prognosis of heart failure and the need to promote the use of effective
      medications and management designed to improve survival.

PMID- 24662471
TI  - A trait based perspective on the biogeography of common and abundant marine
      bacterioplankton clades.
AB  - Marine microbial communities provide much of the energy upon which all higher
      trophic levels depend, particularly in open-ocean and oligotrophic systems, and
      play a pivotal role in biogeochemical cycling. How and why species are
      distributed in the global oceans, and whether net ecosystem function can be
      accurately predicted from community composition are fundamental questions for
      marine scientists. Many of the most abundant clades of marine bacteria, including
      the Prochlorococcus, Synechococcus, SAR11, SAR86 and Roseobacter, have a very
      broad, if not a cosmopolitan distribution. However this is not reflected in an
      underlying genetic identity. Rather, widespread distribution in these organisms
      is achieved by the existence of closely related but discrete ecotypes that
      display niche adaptations. Closely related ecotypes display specific nutritional
      or energy generating mechanisms and are adapted to different physical parameters
      including temperature, salinity, and hydrostatic pressure. Furthermore, biotic
      phenomena such as selective grazing and viral loss contribute to the success or
      failure of ecotypes allowing some to compete effectively in particular marine
      provinces but not in others. An additional layer of complexity is added by ocean
      currents and hydrodynamic specificity of water body masses that bound microbial
      dispersal and immigration. These vary in space and time with respect to intensity
      and direction, making the definition of large biogeographic provinces
      problematic. A deterministic theory aimed at understanding how all these factors
      shape microbial life in the oceans can only proceed through analysis of microbial
      traits, rather than pure phylogenetic assessments. Trait based approaches seek
      mechanistic explanations for the observed temporal and spatial patterns. This
      review will present successful recent advances in phylogenetic and trait based
      biogeographic analyses in some of the most abundant marine taxa. 

PMID- 24662472
TI  - Kuwait National Programme for Healthy Living: first 5-year plan (2013-2017).
AB  - The Kuwait National Programme for Healthy Living is an initiative to promote the
      health and well-being for individuals residing in the country. The plan has been
      created based on current data and available information pertaining to the various
      lifestyles of the populations living in Kuwait and their impact on health in
      general and chronic diseases in particular. Leading a healthy lifestyle is
      important because it means living in an environment, such as the Kuwaiti society,
      where chronic conditions such as obesity, diabetes, hypertension and coronary
      heart diseases are significantly reduced. Several factors regarding lifestyles
      among the various ethnic groups residing in Kuwait have been identified,
      including inactivity resulting from the lack of need for physical exertion in
      daily-life activities and social rituals involving the serving of food amongst
      the various ethnic groups residing in Kuwait. For Kuwaitis and other ethnicities
      as well, traditional social gatherings include serving food as an integral
      element of the social ritual. The environments of school and work also contribute
      to an individual's lifestyle. The goal of the programme is to address the
      contribution of lifestyle choices and the social environment to health with the
      goal of creating a healthy environment that will sustain good health and social
      well-being. This can be accomplished by involving the various stakeholders in
      promoting the aim of the programme. Finally, addressing the research needs for
      healthy lifestyle issues can have a huge impact on the outcome of the programmes
      designed and would aid in creating a healthy living environment.

PMID- 24662473
TI  - Current status of multichannel electrogastrography and examples of its use.
AB  - Electrogastrography (EGG) is a non-invasive diagnostic motility for recording
      gastric myoelectrical activity. Gastric myoelectrical activity was first recorded
      in 1922. Advances in recording equipment enabled widespread use of cutaneous EGG
      after 1985. Later, introduction of multichannel EGG (M-EGG) enabled measurement
      of electrical activity transmission. At present, M-EGG findings are used as
      objective indicators of gastric motility disorders caused by various diseases.
      EGG measures two categories of gastric electrical activity: electrical response
      activity, or spike potentials; and electrical control activity, or slow waves.
      The appearance of abnormal rhythmic electrical activity is indicative of
      abnormalities in gastric motility. The normal frequency range of gastric
      electrical activity (normogastria) is around 3 cycles per?min. Multiple EGG
      parameters assist in the assessment of gastric myoelectrical activity, and
      significant correlations between EGG and other gastric motility tests have been
      demonstrated in many studies. In Japan, however, EGG remains in the exploratory
      stage, and its clinical use is limited. There are large variations in procedures
      and systems used in previous studies, thus there is a need for standardization of
      EGG procedures and technical terminology. Here, we outline the current status of
      EGG and report the M-EGG procedures used in our department in addition to our M
      EGG findings.

PMID- 24662474
TI  - Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"
      contraction of skinned tracheal muscles from guinea pig.
AB  - Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)
      induced contraction and contractile filament organization without affecting the
      Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory
      light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from
      the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26).
      In the present study, we investigated blebbistatin effects on the contractile
      force of skinned tracheal muscle, in which myosin filaments organization is more
      labile than that in the taenia cecum. Blebbistatin at 10 MUM or higher suppressed
      Ca(2+)-induced tension development at any given Ca(2+) concentration, but had
      little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also
      blebbistatin at 10 MUM and higher significantly suppressed GTP-gammaS-induced
      "sensitized" force development. Since the force inhibiting effects of
      blebbistatin on the skinned trachea were much stronger than those in skinned
      taenia cecum, blebbistatin might directly affect myosin filaments organization. 

PMID- 24662476
TI  - Chloride channel blockers promote relaxation of TEA-induced contraction in airway
      smooth muscle.
AB  - Enhanced airway smooth muscle (ASM) contraction is an important component in the
      pathophysiology of asthma. We have shown that ligand gated chloride channels
      modulate ASM contractile tone during the maintenance phase of an induced
      contraction, however the role of chloride flux in depolarization-induced
      contraction remains incompletely understood. To better understand the role of
      chloride flux under these conditions, muscle force (human ASM, guinea pig ASM),
      peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma
      membrane electrical potentials (human cultured ASM) were measured. We found ex
      vivo guinea pig airway rings, human ASM strips and small peripheral airways in
      rat lungs slices relaxed in response to niflumic acid following depolarization
      induced contraction induced by K(+) channel blockade with tetraethylammonium
      chloride (TEA). In isolated human airway smooth muscle cells TEA induce
      depolarization as measured by a fluorescent indicator or whole cell patch clamp
      and this depolarization was reversed by niflumic acid. These findings demonstrate
      that ASM depolarization induced contraction is dependent on chloride channel
      activity. Targeting of chloride channels may be a novel approach to relax
      hypercontractile airway smooth muscle in bronchoconstrictive disorders. 

PMID- 24662475
TI  - Interdigestive migrating motor complex -its mechanism and clinical importance.
AB  - Migrating motor complex (MMC) is well characterized by the appearance of
      gastrointestinal (GI) contractions in the interdigestive state. The physiological
      importance of gastric MMC is a mechanical and chemical cleansing of the empty
      stomach in preparation for the next meal. MMC cycle is mediated via the
      interaction between motilin and 5-hydroxytryptamine (5-HT) by the positive
      feedback mechanism in conscious dogs. Luminal administration of 5-HT initiates
      duodenal phase II and phase III with a concomitant increase of plasma motilin
      release. Duodenal 5-HT concentration is increased during gastric phase II and
      phase III. Intravenous infusion of motilin increases luminal 5-HT content and
      induces phase III. 5-HT4 antagonists significantly inhibit both of gastric and
      intestinal phase III, while 5-HT3 antagonists inhibit only gastric phase III.
      These suggest that gastric MMC is regulated via vagus, 5-HT3/4 receptors and
      motilin, while intestinal MMC is regulated via intrinsic primary afferent neurons
      (IPAN) and 5-HT4 receptors. We propose the possibility that maximally released
      motilin by a positive feedback depletes 5-HT granules in the duodenal EC cells,
      resulting in no more contractions. Stress is highly associated with the
      pathogenesis of functional dyspepsia (FD). Acoustic stress attenuates gastric
      phase III without affecting intestinal phase III in conscious dogs, via reduced
      vagal activity. Subset of FD patients shows reduced vagal activity and impaired
      gastric phase III. The impaired gastric MMC may aggravate dyspeptic symptoms
      following a food ingestion. Maintaining MMC cycle in the interdigestive state is
      an important factor to prevent the postprandial dyspeptic symptoms. 

PMID- 24662477
TI  - Characteristics and safety assessment of intractable proteins in genetically
      modified crops.
AB  - Genetically modified (GM) crops may contain newly expressed proteins that are
      described as "intractable". Safety assessment of these proteins may require some
      adaptations to the current assessment procedures. Intractable proteins are
      defined here as those proteins with properties that make it extremely difficult
      or impossible with current methods to express in heterologous systems; isolate,
      purify, or concentrate; quantify (due to low levels); demonstrate biological
      activity; or prove equivalency with plant proteins. Five classes of intractable
      proteins are discussed here: (1) membrane proteins, (2) signaling proteins, (3)
      transcription factors, (4) N-glycosylated proteins, and (5) resistance proteins
      (R-proteins, plant pathogen recognition proteins that activate innate immune
      responses). While the basic tiered weight-of-evidence approach for assessing the
      safety of GM crops proposed by the International Life Sciences Institute (ILSI)
      in 2008 is applicable to intractable proteins, new or modified methods may be
      required. For example, the first two steps in Tier I (hazard identification)
      analysis, gathering of applicable history of safe use (HOSU) information and
      bioinformatics analysis, do not require protein isolation. The extremely low
      level of expression of most intractable proteins should be taken into account
      while assessing safety of the intractable protein in GM crops. If Tier II (hazard
      characterization) analyses requiring animal feeding are judged to be necessary,
      alternatives to feeding high doses of pure protein may be needed. These
      alternatives are discussed here. 

PMID- 24662478
TI  - Current modeling practice may lead to falsely high benchmark dose estimates.
AB  - Benchmark dose (BMD) modeling is increasingly used as the preferred approach to
      define the point-of-departure for health risk assessment of chemicals. As data
      are inherently variable, there is always a risk to select a model that defines a
      lower confidence bound of the BMD (BMDL) that, contrary to expected, exceeds the
      true BMD. The aim of this study was to investigate how often and under what
      circumstances such anomalies occur under current modeling practice. Continuous
      data were generated from a realistic dose-effect curve by Monte Carlo simulations
      using four dose groups and a set of five different dose placement scenarios,
      group sizes between 5 and 50 animals and coefficients of variations of 5-15%. The
      BMD calculations were conducted using nested exponential models, as most BMD
      software use nested approaches. "Non-protective" BMDLs (higher than true BMD)
      were frequently observed, in some scenarios reaching 80%. The phenomenon was
      mainly related to the selection of the non-sigmoidal exponential model
      (Effect=a.e(b)(.dose)). In conclusion, non-sigmoid models should be used with
      caution as it may underestimate the risk, illustrating that awareness of the
      model selection process and sound identification of the point-of-departure is
      vital for health risk assessment. 

PMID- 24662479
TI  - State of the art Raman techniques for biological applications.
AB  - Raman spectroscopy is a powerful tool for the elucidation of qualitative and
      quantitative information from biological systems and has huge potential in areas
      such as biotechnologies, drug discovery, agro-chemical research and clinical
      diagnostics. This report summarises the principal Raman techniques applied to
      biomedical systems and discusses the challenges that exist to the wide spread
      adoption of Raman spectroscopy. 

PMID- 24662480
TI  - Presence of the neurotoxin BMAA in aquatic ecosystems: what do we really know?
AB  - The neurotoxin beta-N-methylamino-L-alanine (BMAA) is suspected to play a role in
      the neurological diseases amyotrophic lateral sclerosis, Alzheimer's disease, and
      Parkinson's disease. BMAA production by cyanobacteria has been reported and
      contact with cyanobacteria infested waters or consumption of aquatic organisms
      are possible pathways to human exposure. However, there is little consensus
      regarding whether BMAA is present in cyanobacteria or not, and if so, at what
      concentrations. The aim of this review is to indicate the current state of
      knowledge on the presence of BMAA in aquatic ecosystems. Some studies have
      convincingly shown that BMAA can be present in aquatic samples at the ug/g dry
      weight level, which is around the detection limit of some equally credible
      studies in which no BMAA was detected. However, for the majority of the reviewed
      articles, it was unclear whether BMAA was correctly identified, either because
      inadequate analytical methods were used, or because poor reporting of analyses
      made it impossible to verify the results. Poor analysis, reporting and prolific
      errors have shaken the foundations of BMAA research. First steps towards
      estimation of human BMAA exposure are to develop and use selective, inter
      laboratory validated methods and to correctly report the analytical work.

PMID- 24662481
TI  - Toxins produced by Valsa mali var. mali and their relationship with
      pathogenicity.
AB  - Valsa mali var. mali (Vmm), the causal agent of apple tree canker disease,
      produces various toxic compounds, including protocatechuic acid, p-hydroxybenzoic
      acid, p-hydroxyacetophenone, 3-(p-hydroxyphenyl)propanoic acid and
      phloroglucinol. Here, we examined the relationship between toxin production and
      the pathogenicity of Vmm strains and determined their bioactivities in several
      assays, for further elucidating the pathogenesis mechanisms of Vmm and for
      developing new procedures to control this disease. The toxins were quantified
      with the high performance liquid chromatography (HPLC) method, and the results
      showed that the strain with attenuated virulence produced low levels of toxins
      with only three to four kinds of compounds being detectable. In contrast, higher
      amounts of toxins were produced by the more aggressive strain, and all five
      compounds were detected. This indicated a significant correlation between the
      pathogenicity of Vmm strains and their ability to produce toxins. However, this
      correlation only existed in planta, but not in vitro. During the infection of
      Vmm, protocatechuic acid was first detected at three days post inoculation (dpi),
      and the others at seven or 11 dpi. In addition, all compounds produced noticeable
      symptoms on host plants at concentrations of 2.5 to 40 mmol/L, with
      protocatechuic acid being the most effective compound, whereas 3-(p
      hydroxyphenyl)propanoic acid or p-hydroxybenzoic acid were the most active
      compounds on non-host plants. 

PMID- 24662482
TI  - The role of the robotic-assisted transaxillary gasless approach for the removal
      of parathyroid adenomas.
AB  - BACKGROUND: We sought to describe a robotic technique of transaxillary gasless
      parathyroidectomy for the management of primary hyperparathyroidism (PHPT) due to
      a parathyroid adenoma. METHODS: All consecutive patients who underwent robotic
      parathyroidectomy for a parathyroid adenoma by a single surgeon were included.
      Data was obtained by a retrospective review of patients' medical charts. RESULTS:
      Nine patients with confirmed PHPT underwent robotic parathyroidectomy. Curative
      resection was established in all patients with the aid of intraoperative
      parathyroid hormone monitoring. One patient required bilateral cervical
      exploration of multiglandular disease. There were no complications. Patients were
      followed up for a period exceeding 6 months without any evidence of persistent or
      recurrent hyperparathyroidism. CONCLUSIONS: Our initial experience demonstrates
      that this technique is safe and effective for the treatment of PHPT. We believe
      that the use of robotic technology for endoscopic parathyroid surgeries could
      overcome the limitations of conventional techniques in the management of
      parathyroid lesions.

PMID- 24662483
TI  - Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by
      homologous recombination.
AB  - DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major
      threat to genome stability if not properly repaired. We and others have
      previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from
      sequences around DSB sites. DiRNAs are associated with Argonaute (Ago) proteins
      and play an important role in DSB repair, though the mechanism through which they
      act remains unclear. Here, we report that the role of diRNAs in DSB repair is
      restricted to repair by homologous recombination (HR) and that it specifically
      relies on the effector protein Ago2 in mammalian cells. Interestingly, we show
      that Ago2 forms a complex with Rad51 and that the interaction is enhanced in
      cells treated with ionizing radiation. We demonstrate that Rad51 accumulation at
      DSB sites and HR repair depend on catalytic activity and small RNA-binding
      capability of Ago2. In contrast, DSB resection as well as RPA and Mre11 loading
      is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely
      functions directly in mediating Rad51 accumulation at DSBs. Taken together, our
      findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or
      retention at DSBs to facilitate repair by HR. 

PMID- 24662484
TI  - Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin
      interactions at the MYC locus.
AB  - The human 8q24 gene desert contains multiple enhancers that form tissue-specific
      long-range chromatin loops with the MYC oncogene, but how chromatin looping at
      the MYC locus is regulated remains poorly understood. Here we demonstrate that a
      long noncoding RNA (lncRNA), CCAT1-L, is transcribed specifically in human
      colorectal cancers from a locus 515 kb upstream of MYC. This lncRNA plays a role
      in MYC transcriptional regulation and promotes long-range chromatin looping.
      Importantly, the CCAT1-L locus is located within a strong super-enhancer and is
      spatially close to MYC. Knockdown of CCAT1-L reduced long-range interactions
      between the MYC promoter and its enhancers. In addition, CCAT1-L interacts with
      CTCF and modulates chromatin conformation at these loop regions. These results
      reveal an important role of a previously unannotated lncRNA in gene regulation at
      the MYC locus. 

PMID- 24662485
TI  - MARCKS regulates membrane targeting of Rab10 vesicles to promote axon
      development.
AB  - Axon development requires membrane addition from the intracellular supply, which
      has been shown to be mediated by Rab10-positive plasmalemmal precursor vesicles
      (PPVs). However, the molecular mechanisms underlying the membrane trafficking
      processes of PPVs remain unclear. Here, we show that myristoylated alanine-rich C
      kinase substrate (MARCKS) mediates membrane targeting of Rab10-positive PPVs, and
      this regulation is critical for axon development. We found that the GTP-locked
      active form of Rab10 binds to membrane-associated MARCKS, whose affinity depends
      on the phosphorylation status of the MARCKS effector domain. Either genetic
      silencing of MARCKS or disruption of its interaction with Rab10 inhibited axon
      growth of cortical neurons, impaired docking and fusion of Rab10 vesicles with
      the plasma membrane, and consequently caused a loss of membrane insertion of
      axonal receptors responsive to extracellular axon growth factors. Thus, this
      study has identified a novel function of MARCKS in mediating membrane targeting
      of PPVs during axon development. 

PMID- 24662487
TI  - Mitochondrial ATP-dependent proteases in protection against accumulation of
      carbonylated proteins.
AB  - Carbonylation is an irreversible oxidative modification of proteins induced by
      reactive oxygen species (ROS) and reactive nitrogen species (RNS) or by-products
      of oxidative stress. Carbonylation leads to the loss of protein function and is
      used as a marker of oxidative stress. Recent data indicate that carbonylation is
      not only an unfavorable chance process but may also play a significant role in
      the control of diverse physiological processes. In plants, carbonylated proteins
      have been found in all cellular compartments; however, mitochondria, one of the
      major sources of reactive species, show the highest levels of oxidatively
      modified proteins under normal or stress conditions. Carbonylated proteins tend
      to misfold and have to be removed to prevent the formation of harmful insoluble
      aggregates. Mitochondria have developed several pathways that continuously
      monitor and remove oxidatively damaged polypeptides, and the mitochondrial
      protein quality control (mtPQC) system, comprising chaperones and ATP-dependent
      proteases, is the first line of defense. The Lon protease has been recognized as
      a key protease involved in the removal of oxidized proteins in yeast and
      mammalian mitochondria, but not in plants. Recently, it has been reported that
      the inner-membrane human i-AAA and m-AAA and Arabidopsis i-AAA proteases are
      crucial components of the defense against accumulation of carbonylated proteins,
      but the molecular basis of their action is not yet clear. Altogether, the
      mitochondrial AAA proteases secure the mitochondrial proteome against
      accumulation of carbonylated proteins. 

PMID- 24662486
TI  - PKCzeta regulates Notch receptor routing and activity in a Notch signaling
      dependent manner.
AB  - Activation of Notch signaling requires intracellular routing of the receptor, but
      the mechanisms controlling the distinct steps in the routing process is poorly
      understood. We identify PKCzeta as a key regulator of Notch receptor
      intracellular routing. When PKCzeta was inhibited in the developing chick central
      nervous system and in cultured myoblasts, Notch-stimulated cells were allowed to
      undergo differentiation. PKCzeta phosphorylates membrane-tethered forms of Notch
      and regulates two distinct routing steps, depending on the Notch activation
      state. When Notch is activated, PKCzeta promotes re-localization of Notch from
      late endosomes to the nucleus and enhances production of the Notch intracellular
      domain, which leads to increased Notch activity. In the non-activated state,
      PKCzeta instead facilitates Notch receptor internalization, accompanied with
      increased ubiquitylation and interaction with the endosomal sorting protein Hrs.
      Collectively, these data identify PKCzeta as a key regulator of Notch trafficking
      and demonstrate that distinct steps in intracellular routing are differentially
      modulated depending on Notch signaling status. 

PMID- 24662488
TI  - Impact of new hepatitis C treatments in different regions of the world.

PMID- 24662490
TI  - Histomorphology and immunohistochemistry of the lower esophageal sphincter of the
      least shrew (Cryptotis parva).
AB  - The biochemical and histopathological changes in the lower esophageal sphincter
      (LES) in the pathogenesis of gastroesophageal reflux disease have gained
      interest. The least shrew is able to vomit in response to emetogens and provides
      a good model to study the histology of this phenomenon relative to the published
      reports in the commonly used but vomit-incompetent laboratory species. The LES is
      located at the junction of the esophagus and stomach. It typically closes at rest
      and opens in response to swallowing. Our findings demonstrate that the least
      shrew does not have a well-defined LES, lacks esophageal glands and has a mucosal
      valve-like projection from the terminal end of the esophagus before joining the
      gastric epithelium at the lesser curvature. In addition, the least shrew has
      thoracic and abdominal components prior to joining the gastric epithelium. The
      mucosal lining of the esophagus is folded, becoming clearly convoluted and
      forming a bucket-like structure at the level of the esophageocardiac junction
      (ECJ). No significant differences are to be found between the structure and
      thickness of the wall before and after the ECJ. Thus, the ECJ forming the LES is
      relatively less complex than those of other mammals including man. The
      distribution of enterochromaffin (EC) cells is confined to the lamina propria of
      the junction and is not associated with the cardiac glands, suggesting its
      functional involvement with the smooth muscle in and around the ECJ. In
      conclusion, the least shrew's anatomical sphincter appears ill-defined and is
      replaced by a less sturdy valve-like mucosal flap.

PMID- 24662491
TI  - Molecule 16673-34-0: a new tool in our arsenal against inflammation.
AB  - The NLRP3 inflammasome has been shown to modulate IL-1B and IL-18 production,
      both key molecular regulators of inflammation. This editorial discusses a new
      molecule 16673-34-0 that inhibits the NLRP3 inflammasome and decreases caspase 1
      production following ischemia reperfusion or acute peritonitis in mice.

PMID- 24662492
TI  - Effects of Nardostachys chinensis on spontaneous ventricular arrhythmias in rats
      with acute myocardial infarction.
AB  - OBJECTIVES: To investigate the effects and mechanisms of Nardostachys chinensis
      (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial
      infarction (AMI). METHODS: Seventy-two rats were randomly divided into the
      control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24).
      Premature ventricular contractions (PVCs), ventricular tachycardias (VTs),
      ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours
      after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular
      myocardium was measured by immunohistochemistry, Western blot, and real-time RT
      PCR. RESULTS: Compared with the control, metoprolol and NC decreased the VF
      incidence (50% vs. 4.2%, P < 0.001, and 50% vs. 12.5%, P = 0.005, respectively).
      There was a steady decrease in the cumulative number of PVCs and VTs within 4
      hours from ligating in 3 groups. Compared with the control, metoprolol and NC
      reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol
      and NC decreased the infarct size of the left ventricular tissue (55.98% +/-
      6.20% vs. 39.13% +/- 4.53%, P < 0.001, and 55.98% +/- 6.20% vs. 42.39% +/- 3.44%,
      P < 0.001, respectively). The results from immunohistochemistry, Western blot,
      and real-time RT-PCR showed that the protein expression of Cx43 in the control
      group was significantly lower than that in the metoprolol and NC groups in the
      infarcted zone. CONCLUSIONS: NC decreased the incidence of spontaneous
      ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved
      Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data
      of the present study indicated that NC may be a promising drug in the future to
      prevent patients with AMI from lethal ventricular arrhythmias in prehospital
      setting.

PMID- 24662493
TI  - Proarrhythmic effects of aldosterone during myocardial ischemia-reperfusion:
      implication of the sarcolemmal-KATP channels.
AB  - OBJECTIVE: To assess the electrophysiological impact of aldosterone during
      myocardial ischemia-reperfusion. METHODS: We used an in vitro model of "border
      zone" using rabbit right ventricle and standard microelectrodes. RESULTS:
      Aldosterone (10 and 100 nmol/L) shortened ischemic action potential [action
      potential duration at 90% of repolarization (APD90), from 55 +/- 3 to 39 +/- 1 ms
      and 36 +/- 3 ms, respectively, P < 0.05] and induced resting membrane potential
      (RMP) hyperpolarization in the nonischemic zone (from -83 +/- 1 to -93 +/- 7 mV
      and -94 +/- 3 mV, respectively, P < 0.05) and in the ischemic zone during
      reperfusion (from -81 +/- 2 to -88 +/- 2 mV and -91 +/- 2 mV, respectively, P <
      0.05). Bimakalim, an ATP-sensitive potassium (K(ATP)) channel opener, also
      induced RMP hyperpolarization and APD90 shortening. Aldosterone (10 and 100
      nmol/L) increased APD90 dispersion between ischemic and nonischemic zones (from
      96 +/- 3 to 117 +/- 5 ms and 131 +/- 6 ms, respectively, P < 0.05) and
      reperfusion-induced severe premature ventricular contraction occurrence (from 18%
      to 67% and 75%, respectively, P < 0.05). Adding glibenclamide, a nonspecific
      K(ATP) antagonist, to aldosterone superfusion abolished these effects different
      to sodium 5-hydroxydecanoate, a mitochondrial-K(ATP) antagonist. CONCLUSIONS: In
      this in vitro rabbit model of border zone, aldosterone induced RMP
      hyperpolarization and decreased ischemic APD90 evoking the modulation of K
      currents. Glibenclamide prevented these effects different to 5-hydroxydecanoate,
      suggesting that sarcolemmal-K(ATP) channels may be involved in this context.

PMID- 24662494
TI  - Role of mitofusin-2 in high mobility group box-1 protein-mediated apoptosis of T
      cells in vitro.
AB  - BACKGROUND: High mobility group box-1 protein (HMGB1), a ubiquitous nuclear
      protein, which is recognized as a danger-associated molecular pattern (DAMP)
      triggering activation of the innate immune system. Previous studies have shown
      that HMGB1 also plays a role in T cell-mediated immunity, but the effect of HMGB1
      on apoptosis of T cells and its precise mechanism remain to be determined.
      METHODS: Two kinds of apoptosis assay techniques were used, i.e., Annexin V-FITC
      conjunction with PI to identify early apoptotic cells, Hoechst 33342 staining for
      double-stranded DNA to observe nuclear fragmentation or apoptotic body. The
      activation status of caspase-3, caspase-8, as well as caspase-9 was examined by
      colorimetric assay. The dynamic changes in intracellular calcium concentration
      ([Ca(2+)]i) was monitored by flow cytometry. Overexpression of Mfn2 was preformed
      by lentiviral vector transfection. The mRNA and protein levels of Mfn2 were
      determined by RT-PCR and Western-blotting. RESULTS: Treatment of Jurkat T cells
      with recombinant human HMGB1 (rhHMGB1) causes a significant dose-dependent
      increase in percentage of apoptotic cells. When T cells are incubated with HMGB1
      they express decreased mitochondria fusion-related protein mitofusin-2 (Mfn2) and
      activate mitochondrial apoptotic pathway via elevation of [Ca(2+)]i, Bax
      insertion, and activation of caspase. Furthermore, overexpression of Mfn2
      ameliorates the apoptosis of T cells induced by HMGB1. This occurs at least
      partly through Mfn2 keeps Ca(2+) homeostasis in T cells evidenced by monitoring
      [Ca(2+)]i dynamics. CONCLUSION: HMGB1 can trigger apoptosis of T lymphocytes
      through mitochondrial death pathway associated with [Ca(2+)]i elevation. Mfn2
      plays a pivotal role in this process, and it might be a novel therapeutic target
      in T cell apoptosis related disorders.

PMID- 24662495
TI  - Effective reassurance in primary care of low back pain: what messages from
      clinicians are most beneficial at early stages?
AB  - OBJECTIVES: Effective reassurance of patients reporting symptoms, for which no
      clear etiological origin is available, is one of the most important challenges in
      the early phases of nonspecific back pain. However, there is a lack of empirical
      studies on the effects of reassurance and, also, the effects shown were small.
      Improvements are needed with respect to the process of physician-patient
      interaction and to the methods used by the physician. METHODS: We provide a short
      narrative review of the literature with special reference to affective and
      cognitive communication, based on a systematic review of 16 studies. We further
      consider recent evidence in the prognosis of low back pain, the role of physical
      activity, and subgroups-based individual differences in pain coping, questioning
      the information basis of reassurance. RESULTS: A 2-process model of affective and
      cognitive reassurance was supported. Recovery improved in a combination of
      communication of empathy with cognitive reassurance, giving concrete information
      and instructions. In terms of information, recent research indicate that a
      substantial percentage of patients do not recover within the first year after
      onset of back pain. Further, very low and high levels of physical activity are
      associated with pain and disability, associated with cognitive and behavioral
      pain coping. DISCUSSION: Reassurance of patients in early phases of persistent
      back pain might improve from affective and cognitive parts of communication and
      individually tailored information. Subgroup differences with respect to different
      prognosis, associated patterns of adaptive or maladaptive pain coping, and levels
      of health-promoting versus harmful physical activity should be considered more
      carefully.

PMID- 24662496
TI  - A self-regulation perspective on avoidance and persistence behavior in chronic
      pain: new theories, new challenges?
AB  - OBJECTIVE: Behavioral factors such as avoidance and persistence have received
      massive theoretical and empirical attention in the attempts to explain chronic
      pain and disability. The determinants of these pain behaviors remain, however,
      poorly understood. We propose a self-regulation perspective to increase our
      understanding of pain-related avoidance and persistence. METHODS: A narrative
      review. RESULTS: We identified several theoretical views that may help explaining
      avoidance and persistence behavior, and organized these views around 4 concepts
      central in self-regulation theories: (1) identity, (2) affective-motivational
      orientation, (3) goal cognitions, and (4) coping. The review shows that each of
      these self-regulation perspectives allows for a broadened view in which pain
      behaviors are not simply considered passive consequences of fear, but proactive
      strategies to regulate the self when challenged by pain. DISCUSSION: Several
      implications and challenges arising from this review are discussed. In
      particular, a self-regulation perspective does not consider avoidance and
      persistence behavior to be intrinsically adaptive or maladaptive, but argues that
      their effects on disability and well-being rather depend on the goals underlying
      these behaviors. Such view would require a shift in how avoidance and persistence
      behavior are assessed and approached in clinical interventions.

PMID- 24662497
TI  - Outcome measures in randomized-controlled trials of neuropathic pain conditions:
      a systematic review of systematic reviews and recommendations for practice.
AB  - OBJECTIVES: Neuropathic pain (NeP) is a prevalent, disabling, multidimensional
      condition with significant morbidity; however, there appears to be a variable
      approach in the use of outcome measures in NeP trials. A search of systematic
      reviews of interventional randomized-controlled trials for NeP was undertaken to
      investigate the range and types of outcome measures used to determine treatment
      effects. METHODS: Keywords and MESH searches were conducted in 5 electronic
      databases from inception to January 31, 2012. Full-text English-language reviews
      based on various acute and chronic NeP conditions were included. Two independent
      reviewers screened papers for inclusion, extracted data, and assessed the quality
      of reviews. Preferred Reporting Items for Systematic reviews and Meta-Analyses
      (PRISMA) guidelines were used to critically appraise the reviews. RESULTS: A
      total of 46 studies were identified: the majority of reviews (n=28/46, 61%)
      scored well on the PRISMA (PRISMA scores of 20-27/27). Change in levels or
      intensity of pain were used by the majority of studies as the primary outcome
      measure in intervention studies (n=40/46 studies, 87%). Few studies used a
      functional outcome measure as either a primary or secondary outcome measure
      (n=7/46, 15% of studies). DISCUSSION: These results demonstrate that measures of
      pain are predominantly used in trials of NeP conditions and highlight the scant
      usage of functional outcome measures. The lack of standardization for the
      diagnostic criteria in NeP trials is also an issue that needs to be considered
      for future research and guideline development.

PMID- 24662498
TI  - Exercise, not to exercise, or how to exercise in patients with chronic pain?
      Applying science to practice.
AB  - BACKGROUND: Exercise is an effective treatment strategy in various chronic
      musculoskeletal pain disorders, including chronic neck pain, osteoarthritis,
      headache, fibromyalgia and chronic low back pain. Although exercise can benefit
      those with chronic pain (CP), some patients (eg, those with fibromyalgia, myalgic
      encephalomyelitis/chronic fatigue syndrome and chronic whiplash associated
      disorders) encounter exercise as a pain inducing stimulus and report symptom
      flares due to exercise. OBJECTIVES: This paper focuses on the clinical benefits
      and detrimental effects of exercise in patients with CP. It summarizes the
      positive and negative effects of exercise therapy in migraine and tension-type
      headache and provides an overview of the scientific evidence of dysfunctional
      endogenous analgesia during exercise in patients with certain types of CP.
      Further, the paper explains the relationship between exercise and recovery
      highlighting the need to address recovery strategies as well as exercise regimes
      in the rehabilitation of these patients. The characteristics, demands and
      strategies of adequate recovery to compensate stress from exercise and return to
      homeostatic balance will be described. METHODS: narrative review. RESULTS:
      Exercise is shown to be effective in the treatment of chronic tension-type
      headache and migraine. Aerobic exercise is the best option in migraine
      prophylaxis, whereas specific neck and shoulder exercises is a better choice in
      treating chronic tension-type headache. Besides the consensus that exercise
      therapy is beneficial in the treatment of CP, the lack of endogenous analgesia in
      some CP disorders should not be ignored. Clinicians should account for this when
      treating CP patients. Furthermore, optimizing the balance between exercise and
      recovery is of crucial merit in order to avoid stress-related detrimental effects
      and achieve optimal functioning in patients with CP. CONCLUSION: Exercise therapy
      has found to be beneficial in CP, but it should be appropriately and individually
      tailored with emphasis on prevention of symptom flares and applying adequate
      recovery strategies.

PMID- 24662499
TI  - Clinical study evaluating pregabalin efficacy and tolerability for pain
      management in patients undergoing laparoscopic cholecystectomy.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of pregabalin in
      postoperative pain management after laparoscopic cholecystectomy (LC). PATIENTS
      AND METHODS: A prospective, randomized, placebo, controlled, double-blinded study
      was conducted at Anesthesia Department, Laparoscopy Surgery Unit, Ain Shams
      University Hospital. Ninety patients with ASA physical status I-II scheduled for
      elective LC under general anesthesia were included. Patients were randomly
      assigned to the following groups (n=30 each): pregabalin group (P), received 150
      mg pregabalin capsules 2 hours preoperatively, 12 hours postoperatively, and
      twice daily for 2 days; gabapentin group (G), received 1200 mg gabapentin
      capsules (400 mg, *3) 2 hours preoperatively, 12 hours postoperatively, and 400
      mg three times daily for 2 days; and control group (C), received placebo
      capsules. Postoperative pain scores were recorded on a visual analogue scale. The
      following data were recorded: total daily pethidine and diclofenac consumption,
      numeric sedation score, and the postoperative nausea, vomiting, and dizziness
      scores. RESULTS: The 24-hour pethidine consumption was significantly lower
      (P<0.001) in both pregabalin and gabapentin groups versus control. Both groups
      had significantly less (P<0.001) patients with postoperative nausea, vomiting,
      sedation, and dizziness versus control. Overall patient satisfaction with pain
      management was significantly higher (P<0.001) in pregabalin group versus
      gabapentin or control groups. CONCLUSIONS: Gabapentin 1200 mg and pregabalin 150
      mg are effective and safe analgesics for reducing postoperative pain in LC. The
      perioperative oral administration of pregabalin 150 mg in patients undergoing LC
      is an effective and safe method of analgesia with a low incidence of adverse
      effects and reduces postoperative pethidine consumption.

PMID- 24662500
TI  - A methodological critique of the National Institute of Aging and Alzheimer's
      Association Guidelines for Alzheimer's disease, dementia, and mild cognitive
      impairments.
AB  - In 2011, the U.S. National Institute on Aging published guidelines for clinical
      diagnostics for Alzheimer's disease dementia. These guidelines define a continuum
      with three stages-an early, pre-clinical stage with no symptoms, followed by mild
      cognitive impairment, and a final stage of Alzheimer's disease dementia. This
      methodological critique examines the validity of this continuum. No studies exist
      showing the progression of these biomarkers to Alzheimer's disease. There is also
      a lack of empirical evidence showing how biomarkers determine mild cognitive
      impairment, which has multiple etiologies. The guidelines fail to explain
      anomalies where there are biomarkers but no expression of Alzheimer's disease. 

PMID- 24662501
TI  - Information and care: A relational approach.
AB  - This article explores how the provision of information about dementia impacts on
      carers and the caring relationships in which they are involved. Narrative
      interviews were undertaken with 25 carers who had undertaken the Alzheimer's
      Society - run Carer Information and Support Programme in one of seven sites
      across London and the South East. Thematic analysis identified two major themes
      relating to the impact of information on carer and caring relationships
      ('understanding and care' and 'emotional impact of information'), and another
      theme relating to the context within which the information was provided and
      shared ('relational practices in information-giving and receiving'). Findings
      suggest that while information, particularly in the form of new knowledge about
      how dementia progresses, helps to improve understanding and increase confidence,
      competence and a sense of security and achievement in caring practices, it can
      also confound and complicate caring practices in ways that reflect and reinforce
      previously difficult relationships. Providing information in the context of
      carers' support was important for most participants but others were less able to
      benefit from this, especially where they felt unrecognised or where the timing of
      information felt inappropriate to their needs. Our analysis complements and
      extends previous scholarship emphasising the relational nature of care by showing
      how information can both enhance and complicate care relationships, depending on
      both specific care contexts and on how carers experience the context of
      information provision. 

PMID- 24662502
TI  - The bijection from data to parameter space with the standard DEB model quantifies
      the supply-demand spectrum.
AB  - The standard Dynamic Energy Budget (DEB) model assumes that food is converted to
      reserve and a fraction kappa of mobilised reserve of an individual is allocated
      to somatic maintenance plus growth, while the rest is allocated to maturity
      maintenance plus maturation (in embryos and juveniles) or reproduction (in
      adults). The add_my_pet collection of over 300 animal species from most larger
      phyla, and all chordate classes, shows that this model fits energy data very
      well. Nine parameters determine nine data points at abundant food: dry/wet weight
      ratio, age at birth, puberty, death, weight at birth, metamorphosis, puberty,
      ultimate weight and ultimate reproduction rate. We demonstrate that, given a few
      other parameters, these nine data points also determine the nine parameters
      uniquely that are independent of food availability: maturity at birth,
      metamorphosis and puberty, specific assimilation, somatic maintenance and costs
      for structure, allocation fraction of mobilised reserve to soma, energy
      conductance, and ageing acceleration. We provide an efficient algorithm for
      mapping between data and parameter space in both directions and found expressions
      for the boundaries of the parameter and data spaces. One of them quantifies the
      position of species in the supply-demand spectrum, which reflects the
      internalisation of energetic control. We link eco-physiological properties of
      species to their position in this spectrum and discuss it in the context of
      homeostasis. Invertebrates and ray-finned fish turn out to be close to the supply
      end of the spectrum, while other vertebrates, including cartilaginous fish, have
      stronger demand tendencies. We explain why birds and mammals up-regulate
      metabolism during reproduction. We study some properties of the bijection using
      elasticity coefficients. The properties have applications in parameter estimation
      and in the analysis of evolutionary constraints on parameter values; the
      relationship between DEB parameters and data has similarities to that between
      genotype and phenotype. 

PMID- 24662503
TI  - The virus of my virus is my friend: ecological effects of virophage with
      alternative modes of coinfection.
AB  - Virophages are viruses that rely on the replication machinery of other viruses to
      reproduce within eukaryotic hosts. Two different modes of coinfection have been
      posited based on experimental observation. In one mode, the virophage and the
      virus enter the host independently. In the other mode, the virophage adheres to
      the virus so both virophage and virus enter the host together. Here we ask: what
      are the ecological effects of these different modes of coinfection? In
      particular, what ecological effects are common to both infection modes, and what
      are the differences particular to each mode? We develop a pair of biophysically
      motivated ODE models of viral-host population dynamics, corresponding to dynamics
      arising from each mode of infection. We find that both modes of coinfection allow
      for the coexistence of the virophage, virus, and host either at a stable fixed
      point or through cyclical dynamics. In both models, virophage tends to be the
      most abundant population and their presence always reduces the viral abundance
      and increases the host abundance. However, we do find qualitative differences
      between models. For example, via extensive sampling of biologically relevant
      parameter space, we only observe bistability when the virophage and the virus
      enter the host together. We discuss how such differences may be leveraged to help
      identify modes of infection in natural environments from population level data. 

PMID- 24662504
TI  - Hourglass-like constrictions of peripheral nerve in the upper extremity: a
      clinical review and pathological study.
AB  - BACKGROUND: The development of an hourglass-like constriction in the nerve is
      rare, and its origin is unknown. Its clinical manifestations are not well
      documented, and the treatment protocol has not been established. OBJECTIVE: To
      identify the cause, presentation, and possible treatment for patients with nerve
      palsies secondary to an hourglass-like constriction in the affected nerves.
      METHODS: Patients presenting with peripheral nerve palsy caused by an hourglass
      like constriction of nerves were retrospectively investigated in 2 hand centers.
      The patients' presentation and neurological findings were reviewed, and the
      immunohistochemistry of excised specimens was studied. RESULTS: Forty-two
      patients who presented with 47 nerve palsies were examined. Forty-one patients
      experienced a sudden onset of pain in the upper limb, followed by flaccid
      paralysis in the affected muscles. Ten patients had multiple nerve involvement.
      Surgical exploration found 1 or more hourglass-like constrictions in the nerve.
      The treatments included internal neurolysis, neurorrhaphy, and nerve grafting.
      Thirty-one of 42 patients (36 nerves) were followed up for a mean of 48 months
      (range, 8-157 months). Fifteen of 16 nerves treated by neurolysis, 10 of 13
      nerves treated by neurorrhaphy, and 4 of 7 nerves treated by nerve grafting had
      good recovery. CD8-positive T-lymphocyte infiltration was observed in all the
      excised specimens. CONCLUSION: The clinical presentation of patients with
      hourglass-like constrictions in their nerves is similar to that of patients with
      neuralgic amyotrophy. Histochemical analysis suggests that the pathogenesis may
      be immunological in origin. The role of surgery in this condition is uncertain.

PMID- 24662505
TI  - Biomechanical assessment of anchored cervical interbody cages: comparison of 2
      screw and 4-screw designs.
AB  - BACKGROUND: A new anchored cervical interbody polyetheretherketone spacer was
      devised that uses only 2 integrated variable-angle screws diagonally into the
      adjacent vertebral bodies instead of the established device that uses 4 diagonal
      fixed-angle screws. OBJECTIVE: To compare in vitro the stability provided by the
      new 2-screw interbody spacer with that of the 4-screw spacer and a 4-screw
      anterior plate plus independent polyetheretherketone spacer. METHODS: Three
      groups of cadaveric specimens were tested with 2-screw anchored cage (n = 8), 4
      screw anchored cage (n = 8), and standard plate/cage (n = 16). Pure moments (1.5
      Nm) were applied to induce flexion, extension, lateral bending, and axial
      rotation while measuring 3-D motion optoelectronically. RESULTS: In all 3 groups,
      the mean range of motion (ROM) and lax zone were significantly reduced relative
      to the intact spine after discectomy and fixation. The 2-screw anchored cage
      allowed significantly greater ROM (P < .05) than the standard plate during
      flexion, extension, and axial rotation and allowed significantly greater ROM than
      the 4-screw cage during extension and axial rotation. The 4-screw anchored cage
      did not allow significantly different ROM or lax zone than the standard plate
      during any loading mode. CONCLUSION: The 2-screw variable-angle anchored cage
      significantly reduces ROM relative to the intact spine. Greater stability can be
      achieved, especially during extension and axial rotation, by using the 4-screw
      cage or standard plate plus cage.

PMID- 24662506
TI  - Carotid endarterectomy: comparison of complications between transverse and
      longitudinal incision.
AB  - BACKGROUND: Cranial nerve injury (CNI) is the most common neurological
      complication associated with carotid endarterectomy (CEA). Some authors postulate
      that the transverse skin incision leads to increased risk of CNI. OBJECTIVE: We
      compared the incidence of CNI associated with the transverse and longitudinal
      skin incisions in a high-volume cerebrovascular center. METHODS: We reviewed the
      charts of 226 consecutive patients who underwent CEAs between January 2007 and
      August 2009. Pre- and postoperative standardized neurological evaluations were
      performed by faculty neurologists and neurosurgeons. RESULTS: One hundred sixty
      nine of 226 (75%) CEAs were performed with the use of a transverse incision. The
      longitudinal incision was generally reserved for patients with a high-riding
      carotid bifurcation. Mean patient age was 69 years (range, 45-91 years); 62% were
      men; 59% of patients were symptomatic and had high-grade stenosis (70%-99%). CNI
      occurred in 8 cases (3.5%): 5 (3%) in transverse and 3 (5.3%) with longitudinal
      incisions (P = .42). There were 2 marginal mandibular nerve injuries, 1 (0.6%)
      transverse and 1 longitudinal; 5 recurrent laryngeal nerve injuries, 4 transverse
      and 1 longitudinal; and 1 case of hypoglossal nerve injury associated with
      longitudinal incision. One hematoma was associated with CNI. All injuries were
      transient. Fourteen wound hematomas required surgical evacuation. CONCLUSION: The
      transverse skin incision for CEAs is not associated with an increased risk of CNI
      (P =.42). In this study, the incidence of CNI associated with the transverse
      incision was 3% (n = 5) vs 5% (n = 3) for longitudinal incisions. All CNIs were
      temporary.

PMID- 24662507
TI  - Racial and socioeconomic disparities in incidence of hospital-acquired
      complications following cerebrovascular procedures.
AB  - BACKGROUND: Patients with cerebrovascular disease undergo complex surgical
      procedures, often requiring prolonged inpatient hospitalization. Previous studies
      have demonstrated associations between racial/demographic factors and clinical
      outcomes in patients undergoing cerebrovascular procedures (CVPs). The Centers
      for Medicare and Medicaid Services have published a series of 11 hospital
      acquired conditions (HACs) deemed "reasonably preventable" for which related
      costs of treatment are not reimbursed. We hypothesize that race and payer status
      disparities impact HAC frequency in patients undergoing CVPs and that HAC
      incidence is associated with length of stay and hospital costs. OBJECTIVE: To
      assess health disparities in HACs among the cerebrovascular neurosurgical patient
      population. METHODS: Data were collected from the Nationwide Inpatient Sample
      (NIS) database from 2002 to 2010. CVPs and HACs were identified by International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and
      procedure codes. HAC incidence was evaluated according to demographics including
      race, payer status, and median zip code income via multivariable analysis.
      Secondary outcomes of interest included length of stay and resulting inpatient
      charges. RESULTS: From 2002 to 2010, there were 1 290 883 CVP discharges with an
      HAC rate of 0.5%. Significant disparities in HAC frequency existed according to
      ethnicity and insurance provider. Minorities and Medicaid patients had increased
      frequency of HACs (P < .05), as well as prolonged length of stay and higher
      inpatient costs (P < .05). CONCLUSION: HAC incidence is associated with racial
      and socioeconomic factors in patients who undergo CVPs. Awareness of these
      disparities may lead to improved processes and protocol implementation, which
      might help to decrease the frequency of these potentially avoidable events.

PMID- 24662508
TI  - Three-dimensional reconstruction of the topographical cerebral surface anatomy
      for presurgical planning with free OsiriX Software.
AB  - BACKGROUND: During surgery for intrinsic brain lesions, it is important to
      distinguish the pathological gyrus from the surrounding normal sulci and gyri.
      This task is usually tedious because of the pia-arachnoid membranes with their
      arterial and venous complexes that obscure the underlying anatomy. Moreover, most
      tumors grow in the white matter without initially distorting the cortical
      anatomy, making their direct visualization more difficult. OBJECTIVE: To create
      and evaluate a simple and free surgical planning tool to simulate the anatomy of
      the surgical field with and without vessels. METHODS: We used free computer
      software (OsiriX Medical Imaging Software) that allowed us to create 3
      dimensional reconstructions of the cerebral surface with and without cortical
      vessels. These reconstructions made use of magnetic resonance images from 51
      patients with neocortical supratentorial lesions operated on over a period of 21
      months (June 2011 to February 2013). The 3-dimensional (3-D) anatomic images were
      compared with the true surgical view to evaluate their accuracy. In all patients,
      the landmarks determined by 3-D reconstruction were cross-checked during surgery
      with high-resolution ultrasonography; in select cases, they were also checked
      with indocyanine green videoangiography. RESULTS: The reconstructed neurovascular
      structures were confirmed intraoperatively in all patients. We found this
      technique to be extremely useful in achieving pure lesionectomy, as it defines
      tumor's borders precisely. CONCLUSION: A 3-D reconstruction of the cortical
      surface can be easily created with free OsiriX software. This technique helps the
      surgeon perfect the mentally created 3-D picture of the tumor location to carry
      out cleaner, safer surgeries.

PMID- 24662509
TI  - Computational fractal-based analysis of brain arteriovenous malformation
      angioarchitecture.
AB  - BACKGROUND: Neuroimaging is the gold standard for diagnosis and follow-up of
      brain arteriovenous malformations (bAVMs), but no objective parameter has been
      validated for the assessment of the nidus angioarchitecture and for
      prognostication following treatment. The fractal dimension (FD), which is a
      mathematical parameter able to quantify the space-filling properties and
      roughness of natural objects, may be useful in quantifying the geometrical
      complexity of bAVMs nidus. OBJECTIVE: To propose FD as a neuroimaging biomarker
      of the nidus angioarchitecture, which might be related to radiosurgical outcome.
      METHODS: We retrospectively analyzed 54 patients who had undergone stereotactic
      radiosurgery for the treatment of bAVMs. The quantification of the geometric
      complexity of the vessels forming the nidus, imaged in magnetic resonance
      imaging, was assessed by means of the box-counting method to obtain the fractal
      dimension. RESULTS: FD was found to be significantly associated with the size (P
      = .03) and volume (P < .001) of the nidus, in addition to several
      angioarchitectural parameters. A nonsignificant association between clinical
      outcome and FD was observed (area under the curve, 0.637 [95% confidence
      interval, 0.49-0.79]), indicative of a potential inverse relationship between FD
      and bAVM obliteration. CONCLUSION: In our exploratory methodological research, we
      showed that the FD is an objective computer-aided parameter for quantifying the
      geometrical complexity and roughness of the bAVM nidus. The results suggest that
      more complex bAVM angioarchitecture, having higher FD values, might be related to
      decreased response to radiosurgery and that the FD of the bAVM nidus could be
      used as a morphometric neuroimaging biomarker.

PMID- 24662510
TI  - It is time to reevaluate the management of patients with brain metastases.
AB  - There are many elements to the science that drives the clinical care of patients
      with brain metastases. Although part of an understanding that continues to
      evolve, a number of key historical misconceptions remain that commonly drive
      physicians' and researchers' attitudes and approaches. By understanding how these
      relate to current practice, we can better comprehend our available science to
      provide both better research and care. These past misconceptions include:
      Misconception 1: Once a primary cancer spreads to the brain, the histology of
      that primary tumor does not have much impact on response to chemotherapy,
      sensitivity to radiation, risk of further brain relapse, development of
      additional metastatic lesions, or survival. All tumor primary histologies are the
      same once they spread to the brain. They are the same in terms of the number of
      tumors, radiosensitivity, chemoresponsiveness, risk of further brain relapse, and
      survival. Misconception 2: The number of brain metastases matters. This number
      matters in terms of subsequent brain relapse, survival, and cognitive
      dysfunction; the precise number of metastases can also be used as a limit in
      determining which patients might be eligible for a particular treatment option.
      Misconception 3: Cancer in the brain is always a diffuse problem due to the
      presence of micrometastases. Misconception 4: Whole-brain radiation therapy
      invariably causes disabling cognitive dysfunction if a patient lives long enough.
      Misconception 5: Most brain metastases are symptomatic. Thus, it is not worth
      screening patients for brain metastases, especially because the impact on
      survival is minimal. The conduct and findings of past clinical research have led
      to conceptions that affect clinical care yet appear limiting.

PMID- 24662511
TI  - Cost-effective method for the preparation of uniformly labeled myristoylated
      proteins for NMR measurements.
AB  - Nuclear magnetic resonance (NMR) is a powerful technique for solving protein
      structures or studying their interactions. However, it requires molecules labeled
      with NMR sensitive isotopes like carbon (13)C and nitrogen (15)N. The recombinant
      expression of labeled proteins is simple to perform but requires quite expensive
      chemicals. When there is a need for special labeled chemicals, like uniformly
      (13)C-labeled myristic acid, the price significantly rises. Here we describe a
      cost-effective method for the recombinant expression of uniformly labeled
      myristoylated proteins in Escherichia coli demonstrated on the production of
      Mason-Pfizer monkey virus matrix protein. We used the ability of E. coli to
      naturally synthetize myristic acid. When grown in isotopically labeled medium the
      myristic acid will be labelled as well. Bacteria were co-transfected with plasmid
      carrying gene for yeast N-myristoyltransferase which ensures myristoylation of
      expressed protein. This process provided 1.8mg of the myristoylated, doubly
      labeled ((13)C/(15)N)M-PMV matrix protein from 1L of (15)N/(13)C labeled M9
      medium. The price represents approximately 50% cost reduction of conventional
      method using commercially available [U-(13)C]myristic acid. 

PMID- 24662512
TI  - Conditional probability distribution (CPD) method in temperature based death time
      estimation: Error propagation analysis.
AB  - Bayesian estimation applied to temperature based death time estimation was
      recently introduced as conditional probability distribution or CPD-method by
      Biermann and Potente. The CPD-method is useful, if there is external information
      that sets the boundaries of the true death time interval (victim last seen alive
      and found dead). CPD allows computation of probabilities for small time intervals
      of interest (e.g. no-alibi intervals of suspects) within the large true death
      time interval. In the light of the importance of the CPD for conviction or
      acquittal of suspects the present study identifies a potential error source.
      Deviations in death time estimates will cause errors in the CPD-computed
      probabilities. We derive formulae to quantify the CPD error as a function of
      input error. Moreover we observed the paradox, that in cases, in which the small
      no-alibi time interval is located at the boundary of the true death time
      interval, adjacent to the erroneous death time estimate, CPD-computed
      probabilities for that small no-alibi interval will increase with increasing
      input deviation, else the CPD-computed probabilities will decrease. We therefore
      advise not to use CPD if there is an indication of an error or a contra-empirical
      deviation in the death time estimates, that is especially, if the death time
      estimates fall out of the true death time interval, even if the 95%-confidence
      intervals of the estimate still overlap the true death time interval. 

PMID- 24662513
TI  - The structure and substrate specificity of human Cdk12/Cyclin K.
AB  - Phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin
      dependent kinases is important for productive transcription. Here we determine
      the crystal structure of Cdk12/CycK and analyse its requirements for substrate
      recognition. Active Cdk12/CycK is arranged in an open conformation similar to
      that of Cdk9/CycT but different from those of cell cycle kinases. Cdk12 contains
      a C-terminal extension that folds onto the N- and C-terminal lobes thereby
      contacting the ATP ribose. The interaction is mediated by an HE motif followed by
      a polybasic cluster that is conserved in transcriptional CDKs. Cdk12/CycK showed
      the highest activity on a CTD substrate prephosphorylated at position Ser7,
      whereas the common Lys7 substitution was not recognized. Flavopiridol is most
      potent towards Cdk12 but was still 10-fold more potent towards Cdk9. T-loop
      phosphorylation of Cdk12 required coexpression with a Cdk-activating kinase.
      These results suggest the regulation of Pol II elongation by a relay of
      transcriptionally active CTD kinases. 

PMID- 24662514
TI  - Transcriptional diversity of long-term glioblastoma survivors.
AB  - BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor
      prognosis. However, a small number of patients live much longer than the median
      survival. A better understanding of these long-term survivors (LTSs) may provide
      important insight into the biology of GBM. METHODS: We identified 7 patients with
      GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48
      months. We characterized the transcriptome of each patient and determined rates
      of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified
      LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository
      for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal
      characteristics of these LTSs. RESULTS: The median overall survival of our cohort
      was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n =
      2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the
      TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification
      identities. The majority of the MSKCC LTSs (71%) were found to have methylation
      of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH
      mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was
      found to be differentially expressed in the MSKCC and TCGA LTSs. CONCLUSIONS:
      While IDH mutant proneural tumors impart a better prognosis in the short-term,
      survival beyond 4 years does not require IDH mutation and is not dictated by a
      single transcriptional subclass. In contrast, MGMT methylation continues to have
      strong prognostic value for survival beyond 4 years. These findings have
      substantial impact for understanding GBM biology and progression.

PMID- 24662515
TI  - Established and emerging biomarkers for the prediction of type 1 diabetes: a
      systematic review.
AB  - Type 1 diabetes (T1D) is an autoimmune disease with a prolonged and variable
      latent period that culminates in the destruction of pancreatic beta-cells and the
      development of hyperglycemia. There is a need for diagnostic biomarkers to detect
      more accurately individuals with prediabetes to expedite targeting for prevention
      and intervention strategies. To assess the current ability to predict the
      insidious development of T1D, we conducted a comprehensive systematic review for
      established and prospective predictive markers of T1D using the Medline, OVID,
      and EMBASE databases. Resulting citations were screened for relevance to subject.
      Our research generated five major categories of markers that are either currently
      used or forthcoming: genetic, autoantibody, risk score quantification, cellular
      immunity, and beta-cell function. The current standard used to assess T1D onset
      or predisposition focuses on autoimmune pathology and disease-associated
      autoantibodies. Research studies in general go beyond autoantibody screening and
      assess genetic predisposition, and quantitate risk of developing disease based on
      additional factors. However, there are few currently used techniques that assess
      the root of T1D: beta-cell destruction. Thus, novel techniques are discussed with
      the potential to gauge degrees of beta-cell stress and failure via protein, RNA,
      and DNA analyses. 

PMID- 24662517
TI  - Comparison of complications of the suprameatal approach and mastoidectomy with
      posterior tympanotomy approach in cochlear implantation: a meta-analysis.
AB  - BACKGROUND: Cochlear implantation (CI) is a popular procedure to preserve hearing
      in patients with severe-to-profound hearing loss. Evidence shows that the
      suprameatal approach (SMA) may help reducing the risk of the incidence of
      complications and shortening the surgery time, but there is still dispute.
      OBJECTIVES: The aim of this study was to compare the incidence of complications
      of SMA and the mastoidectomy with posterior tympanotomy approach (MPTA), and to
      find whether SMA yields better outcomes than MPTA. METHODS: We searched PubMed,
      the Cochrane Library, the Web of Science and Chinese Biomedical Literature
      databases, Chinese National Knowledge Infrastructure, the Chinese Science and
      Technology Journal Full-Text database, and Wangfang database. The latest data was
      accessed in March 2013. Review Manager 5.1 software was used for comprehensive
      quantification data analysis. RESULTS: Three studies were included in the meta
      analysis, composed of 799 participants and reporting major and minor
      complications. The meta-analysis indicated no statistically significant
      difference in major and minor complications between the two approaches, except
      for facial nerve and chorda tympani injuries (OR = 0.13; 95% CI: 0.02, 0.67; p =
      0.02; I(2) = 0%). CONCLUSIONS: Current evidence suggests that SMA may be clearly
      a good alternative to the classical surgery technique for CI in terms of reducing
      the incidence of facial nerve injury and chorda tympani sacrifice.

PMID- 24662518
TI  - Cerebral oximetry levels during CPR are associated with return of spontaneous
      circulation following cardiac arrest: an observational study.
AB  - OBJECTIVES: Cerebral oximetry using near-infrared spectroscopy measures regional
      cerebral oxygen saturation (rSO2) non-invasively and may provide information
      regarding the quality of cerebral oxygen perfusion. We determined whether the
      level of rSO2 obtained during cardiopulmonary resuscitation is associated with
      return of spontaneous circulation (ROSC) and survival in Emergency Department
      (ED) patients presenting with cardiac arrest. METHODS: We conducted a
      retrospective, observational study of adult ED patients presenting at an academic
      medical centre with cardiac arrest in whom continuous cerebral oximetry was
      performed. Demographic and clinical data including age, gender, presenting rhythm
      and mean rSO2 readings were abstracted. Cerebral oxygenation was measured with a
      commercially available oximeter. RESULTS: A convenience study sample included 59
      patients ages 18-102 years (mean age 68.7+/-14.9 years); 50 (84.7%) were men.
      Presenting rhythms included pulseless electrical activity (21), asystole (20) and
      ventricular fibrillation/tachycardia (17). 24 patients (40.6%) had ROSC and only
      1 (1.7%) survived to hospital discharge. Patients with and without ROSC were
      similar in age and presenting cardiac rhythms. The mean of mean rSO2 levels was
      higher in patients with ROSC, 43.8 (95% CI 40.1 to 47.6) compared with those
      without ROSC, 34.2 (95% CI 30.6 to 37.8); p=0.001. 91.7% of patients with ROSC
      had a rSO2 of 30% or greater compared with 62.9% in those without ROSC (p=0.01).
      The area under the curve for mean rSO2 as a predictor of ROSC was 0.76 (95% CI
      0.64 to 0.89). CONCLUSIONS: In ED patients with cardiac arrest higher cerebral
      oxygen saturations are associated with higher rates of ROSC.

PMID- 24662519
TI  - Characterization of St-Valerien-like virus genome detected in Japan.
AB  - A novel calicivirus, St-Valerien-like virus (SVV), has been identified in
      asymptomatic swine in Canada, Italy and the U.S.A. In this study, we
      characterized a new SVV strain (NUP-24/JP) detected in fecal samples of swine in
      Japan. The NUP-24/JP genome had 6,409 nucleotides and 2 open reading frames (ORF1
      and ORF2). ORF1 and ORF2 consist of 5,940 and 453 nucleotides, respectively.
      Phylogenetic analysis revealed that NUP-24/JP was closely related to other SVV
      strains, particularly to U.S.A. strain NC-WGS93C/US. This finding suggests that
      SVV is prevalent in swine worldwide. Using a baculovirus expression system, we
      successfully produced virus-like particles, which would be useful for
      seroepidemiological studies of SVV. 

PMID- 24662516
TI  - Accumulation of oligomer-prone alpha-synuclein exacerbates synaptic and neuronal
      degeneration in vivo.
AB  - In Parkinson's disease and dementia with Lewy bodies, alpha-synuclein aggregates
      to form oligomers and fibrils; however, the precise nature of the toxic alpha
      synuclein species remains unclear. A number of synthetic alpha-synuclein
      mutations were recently created (E57K and E35K) that produce species of alpha
      synuclein that preferentially form oligomers and increase alpha-synuclein
      mediated toxicity. We have shown that acute lentiviral expression of alpha
      synuclein E57K leads to the degeneration of dopaminergic neurons; however, the
      effects of chronic expression of oligomer-prone alpha-synuclein in synapses
      throughout the brain have not been investigated. Such a study could provide
      insight into the possible mechanism(s) through which accumulation of alpha
      synuclein oligomers in the synapse leads to neurodegeneration. For this purpose,
      we compared the patterns of neurodegeneration and synaptic damage between a newly
      generated mThy-1 alpha-synuclein E57K transgenic mouse model that is prone to
      forming oligomers and the mThy-1 alpha-synuclein wild-type mouse model (Line 61),
      which accumulates various forms of alpha-synuclein. Three lines of alpha
      synuclein E57K (Lines 9, 16 and 54) were generated and compared with the wild
      type. The alpha-synuclein E57K Lines 9 and 16 were higher expressings of alpha
      synuclein, similar to alpha-synuclein wild-type Line 61, and Line 54 was a low
      expressing of alpha-synuclein compared to Line 61. By immunoblot analysis, the
      higher-expressing alpha-synuclein E57K transgenic mice showed abundant
      oligomeric, but not fibrillar, alpha-synuclein whereas lower-expressing mice
      accumulated monomeric alpha-synuclein. Monomers, oligomers, and fibrils were
      present in alpha-synuclein wild-type Line 61. Immunohistochemical and
      ultrastructural analyses demonstrated that alpha-synuclein accumulated in the
      synapses but not in the neuronal cells bodies, which was different from the alpha
      synuclein wild-type Line 61, which accumulates alpha-synuclein in the soma.
      Compared to non-transgenic and lower-expressing mice, the higher-expressing alpha
      synuclein E57K mice displayed synaptic and dendritic loss, reduced levels of
      synapsin 1 and synaptic vesicles, and behavioural deficits. Similar alterations,
      but to a lesser extent, were seen in the alpha-synuclein wild-type mice.
      Moreover, although the oligomer-prone alpha-synuclein mice displayed
      neurodegeneration in the frontal cortex and hippocampus, the alpha-synuclein wild
      type only displayed neuronal loss in the hippocampus. These results support the
      hypothesis that accumulating oligomeric alpha-synuclein may mediate early
      synaptic pathology in Parkinson's disease and dementia with Lewy bodies by
      disrupting synaptic vesicles. This oligomer-prone model might be useful for
      evaluating therapies directed at oligomer reduction. 

PMID- 24662520
TI  - Ultrasonographic evaluation of equine fetal growth throughout gestation in normal
      mares using a convex transducer.
AB  - It has not been common to perform regular ultrasound examination of the fetus in
      equine practice, due to the increasing volume of the uterus caused by fetal
      development. The convex three-dimensional transducer is bulb-shaped and is able
      to observe wide areas. In addition, its operation is simple, making it easy to
      create appropriate angles for various indices using a transrectal approach. The
      aim of this study was to measure Thoroughbred fetal growth indices throughout
      gestation using a convex transducer and to clarify the detectable period of some
      indices for clinical use. We demonstrated changes in fetal indices, such as crown
      rump length (CRL), fetal heart rate (FHR), fetal eye and kidney and the combined
      thickness of uterus and placenta (CTUP). CTUP increased from 30 weeks of
      gestation, and FHR peaked at 8 weeks and then decreased to term. CRL could be
      observed until 13 weeks due to its wide angle, longer than in previous reports.
      Fetal eye and kidney could be observed from 10 and 28 weeks, respectively, and
      these increased with pregnancy progress. The present results showed the advantage
      of transrectal examination using a convex transducer for evaluation of normal
      fetal development. Although ultrasonographic examination in mid- to late
      gestation is not common in equine reproductive practice, our comprehensive
      results would be a useful basis for equine pregnancy examination. 

PMID- 24662521
TI  - Tumour-educated macrophages display a mixed polarisation and enhance pancreatic
      cancer cell invasion.
AB  - At the time of diagnosis, almost 80% of pancreatic cancer patients present with
      new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic
      cancer are both associated with low-grade inflammation. Tumour-associated
      macrophages (TAMs) have a key role in cancer-related inflammation, immune escape,
      matrix remodelling and metastasis. In this study, the interplay between tumour
      cells and immune cells under the influence of different glucose levels was
      investigated. Human peripheral blood mononuclear cells were exposed in vitro to
      conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or
      high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour
      derived factors stimulated differentiation of macrophages, with a mixed classical
      (M1-like) and alternatively activated (M2-like) phenotype polarisation
      (CD11c(+)CD206(+)). High-glucose conditions further enhanced the tumour-driven
      macrophage enrichment and associated interleukin (IL)-6 and IL-8 cytokine levels.
      In addition, hyperglycaemia enhanced the responsiveness of tumour-educated
      macrophages to lipopolysaccharide, with elevated cytokine secretion compared with
      normal glucose levels. Tumour-educated macrophages were found to promote
      pancreatic cancer cell invasion in vitro, which was significantly enhanced at
      high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype
      polarisation and reduced the tumour cell invasion at normal, but not high,
      glucose levels. In conclusion, this study demonstrates that pancreatic cancer
      cells stimulate differentiation of macrophages with pro-tumour properties that
      are further enhanced by hyperglycaemia. These findings highlight important
      crosstalk between tumour cells and TAMs in the local tumour microenvironment that
      may contribute to disease progression in pancreatic cancer patients with
      hyperglycaemia and T2D.

PMID- 24662522
TI  - Postdischarge feeding of growing "preemies": concerns with limiting fat intake.

PMID- 24662523
TI  - Multiple toxin-antitoxin systems in Mycobacterium tuberculosis.
AB  - The hallmark of Mycobacterium tuberculosis is its ability to persist for a long
      term in host granulomas, in a non-replicating and drug-tolerant state, and later
      awaken to cause disease. To date, the cellular factors and the molecular
      mechanisms that mediate entry into the persistence phase are poorly understood.
      Remarkably, M. tuberculosis possesses a very high number of toxin-antitoxin (TA)
      systems in its chromosome, 79 in total, regrouping both well-known (68) and novel
      (11) families, with some of them being strongly induced in drug-tolerant
      persisters. In agreement with the capacity of stress-responsive TA systems to
      generate persisters in other bacteria, it has been proposed that activation of TA
      systems in M. tuberculosis could contribute to its pathogenesis. Herein, we
      review the current knowledge on the multiple TA families present in this
      bacterium, their mechanism, and their potential role in physiology and virulence.

PMID- 24662525
TI  - Disposition and acute toxicity of imidacloprid in female rats after single
      exposure.
AB  - Single dose of imidacloprid (IMI-20mg/kg bodyweight) was orally administered in
      female rats. Its disposition along with two metabolites 6-chloro nicotinic acid
      (6-CNA) and 6-hydroxy nicotinic acid (6-HNA) was monitored in organs (brain,
      liver, kidney, and ovary) and bodily fluids (blood, urine) at 6, 12, 24 and 48h
      and faeces at 24 and 48h. Maximum concentration (Cmax) of IMI and metabolites in
      each organ and bodily fluid occurred after 12h. Area under curve (AUC) of IMI
      ranged from 35 to 358MUg/ml/h; 6-CNA: 27.12-1006.42MUg/ml/h and 6-HNA: 14.98
      302.74MUg/ml/h in different organs and bodily fluids. Clearance rate of IMI was
      maximum in ovary followed by kidney, liver, brain, faeces, blood and urine.
      Percent inhibition of acetyl-cholinesterase (AChE) was comparable in brain and
      Red Blood Cells (RBC) at 6-48h which suggests the RBC-AChE as valid biomarker for
      assessing IMI exposure. It is evident that IMI was absorbed, metabolized, and
      excreted showing increased level of serum enzymes like Glutamic oxaloacetic
      transaminase (GOT), Glutamic pyruvic transaminase (GPT) and biochemical
      constituents like billirubin and Blood Urea Nitrogen (BUN) at 48h. These data
      suggest that IMI is widely distributed, metabolized and induced toxicology
      effects at 20mg/kg bodyweight to female rats. 

PMID- 24662524
TI  - The effects of the toxic cyanobacterium Limnothrix (strain AC0243) on Bufo
      marinus larvae.
AB  - Limnothrix (strain AC0243) is a cyanobacterium, which has only recently been
      identified as toxin producing. Under laboratory conditions, Bufo marinus larvae
      were exposed to 100,000 cells mL(-1) of Limnothrix (strain AC0243) live cultures
      for seven days. Histological examinations were conducted post mortem and revealed
      damage to the notochord, eyes, brain, liver, kidney, pancreas, gastrointestinal
      tract, and heart. The histopathological results highlight the toxicological
      impact of this strain, particularly during developmental stages. Toxicological
      similarities to beta-N-Methylamino-L-alanine are discussed.

PMID- 24662526
TI  - Analysis of nondiagnostic results in a large series of thyroid fine-needle
      aspiration cytology performed over 9 years in a single center.
AB  - OBJECTIVE: Thyroid fine-needle aspiration cytology (FNAC) is the most valuable,
      cost-effective and accurate method for the evaluation of patients with thyroid
      nodules. One of its limitations is that up to 20% of results are nondiagnostic or
      unsatisfactory. The aim of this study was to analyze the number of thyroid FNAC
      specimens with nondiagnostic results obtained on an outpatient basis and how many
      of these had to be repeated according to their results. STUDY DESIGN: This was a
      retrospective analysis of diagnostic reports of nondiagnostic thyroid FNAC
      specimens obtained between 1 January 2004 and 31 December 2012 which were
      retrieved by means of a computerized search. The FNAC results and the age and sex
      of the patients were collected. RESULTS: From a total of 15,292 thyroid FNAC
      specimens, 6.8% (n = 1,033) corresponded to nondiagnostic cases. Eligible
      diagnostic reports for analysis included 877 cases (106 were repetitions of
      previous nondiagnostic FNAC). After an initial nondiagnostic finding for 771 FNAC
      smears, 29.5% (n = 225) were repeated with the following results: 43.6%
      insufficient, 49.3% benign, 6.2% follicular neoplasm, 0.4% suspicious for
      malignancy and 0.4% malignant. Twenty-two patients underwent a second repeated
      FNAC. Here the findings were: 36.4% insufficient, 59.1% benign, 4.5% follicular
      neoplasm, 0.0% suspicious for malignancy and 0.0% malignant. CONCLUSIONS: There
      was a low rate of repeated FNAC among the group of nondiagnostic cases. With
      repeated FNAC, the rate of nondiagnostic cases and the number of results that
      potentially demand surgery diminish.

PMID- 24662527
TI  - Proteomic characterization of the subpellicular cytoskeleton of Toxoplasma gondii
      tachyzoites.
AB  - Toxoplasma, the causative agent of toxoplasmosis in animals and humans, has a
      subpellicular cytoskeleton that is involved in motility, cell shape and invasion.
      Knowledge of components of the cytoskeleton is necessary to understand the
      invasion mechanisms as well as for the identification of possible therapeutic
      targets. To date, most cytoskeletal components of Toxoplasma remain unidentified
      due mainly to the lack of reproducible methods for their isolation. Based on the
      successful isolation of the cytoskeleton, it was possible to report for the first
      time, the proteomic characterization of the subpellicular cytoskeleton of
      Toxoplasma formed by 95 cytoskeletal proteins through proteomic analysis by
      tandem mass spectrometry of one dimension SDS PAGE. By bioinformatic analysis of
      the data, proteins were classified as: 18 conventional cytoskeletal proteins; 10
      inner membrane complex proteins, including 7 with alveolin repeats; 5 new
      proteins with alveolin like repeats; 37 proteins associated with other organelles
      and 25 novel proteins of unknown function. One of the alveolin like proteins not
      previously described in Toxoplasma named TgArticulin was partially characterized
      with a specific monoclonal antibody. Presence of TgArticulin was exclusively
      associated with the cytoskeleton fraction with a cortical distribution. Functions
      for the several molecules identified are proposed. BIOLOGICAL SIGNIFICANCE: This
      manuscript describes, for the first time, the proteome of the subpellicular
      cytoskeleton of Toxoplasma gondii. The importance of this study is related to the
      role of the cytoskeleton in the highly invasive capability of a parasite that
      causes abortion, blindness, and death by encephalitis in immunocompromised
      patients. Proteomic characterization of the cytoskeleton of T. gondii tachyzoites
      was possible by the development of a successful procedure for the isolation of
      the subpellicular cytoskeleton. Knowledge of the composition of the cytoskeleton
      of Toxoplasma is fundamental for the understanding of the motility and host cell
      invasion mechanisms, and for the future design and development of toxoplasmicidal
      drugs with effects against specific components of the cytoskeleton of this
      parasite that are absent in mammal host cells.

PMID- 24662528
TI  - Does the level of wealth inequality within an area influence the prevalence of
      depression amongst older people?
AB  - This paper considers whether the extent of inequality in house prices within
      neighbourhoods of England is associated with depressive symptoms in the older
      population using the English Longitudinal Study of Ageing. We consider two
      competing hypotheses: first, the wealth inequality hypothesis which proposes that
      neighbourhood inequality is harmful to health and, second, the mixed
      neighbourhood hypothesis which suggests that socially mixed neighbourhoods are
      beneficial for health outcomes. Our results are supportive of the mixed
      neighbourhood hypothesis, we find a significant association between neighbourhood
      inequality and depression with lower levels of depression amongst older people in
      neighbourhoods with greater house price inequality after controlling for
      individual socio-economic and area correlates of depression. The association
      between area inequality and depression is strongest for the poorest individuals,
      but also holds among the most affluent. Our results are in line with research
      that suggests there are social and health benefits associated with economically
      mixed communities. 

PMID- 24662529
TI  - Using multi-level data to estimate the effect of an 'alcogenic' environment on
      hazardous alcohol consumption in the former Soviet Union.
AB  - PURPOSE: The purpose of this study was to assess whether alcohol-related
      community characteristics act collectively to influence individual-level alcohol
      consumption in the former Soviet Union (fSU). METHODS AND RESULTS: Using multi
      level data from nine countries in the fSU we conducted a factor analysis of seven
      alcohol-related community characteristics. The association between any latent
      factors underlying these characteristics and two measures of hazardous alcohol
      consumption was then analysed using a population average regression modelling
      approach. Our factor analysis produced one factor with an eigenvalue >1
      (EV=1.28), which explained 94% of the variance. This factor was statistically
      significantly associated with increased odds of CAGE problem drinking (OR=1.40
      (1.08-1.82)). The estimated association with EHD was not statistically
      significant (OR=1.10 (0.85-1.44)). CONCLUSIONS: Our findings suggest that a high
      number of beer, wine and spirit advertisements and high alcohol outlet density
      may work together to create an 'alcogenic' environment that encourages hazardous
      alcohol consumption in the fSU.

PMID- 24662530
TI  - Rupture, resilience, and risk: relationships between mental health and migration
      among gay-identified men in North America.
AB  - An established body of research in psychology, psychiatry and epidemiology links
      social stigma and stress with poor mental and sexual health outcomes among gay
      identified men. Less work considers how these linkages are mediated by place and
      almost none considers the role of movement across places. This qualitative study,
      based on the migration narratives of 48 gay-identified men living in Ottawa,
      Ontario, Canada, and Washington, D.C., U.S.A. gives more careful consideration to
      the ways in which mental and emotional health issues (e.g., anxiety, depression,
      substance use) in this population both precipitate migration and stem from
      migration. The narratives show that decisions to migrate often emerge from men's
      experiences of place-based minority stress and associated health outcomes. At the
      same time, moving to urban gay communities, when coupled with other life
      circumstances, can create or reinforce physical and emotional insecurities that
      lead to low self-esteem, substance use and sexual risk-taking. 

PMID- 24662536
TI  - Parkinson disease: Gene therapy for Parkinson disease--a hope, or a dream?

PMID- 24662540
TI  - Pediatric disaster planning for the win.

PMID- 24662541
TI  - Bridging nursing's digital generation gap.

PMID- 24662542
TI  - The only constant is change...make it last with process improvement.

PMID- 24662543
TI  - Developing evidence-based tools from EHR data.

PMID- 24662545
TI  - Nurse comfort...more than helpful hands.
AB  - Nurses first focus on patients and often forget about caring for themselves. This
      article examines the issue of burnout and describes how nurse comfort can combat
      it.

PMID- 24662546
TI  - Under pressure: nursing interventions help prevent HAPUs.
AB  - Read this article to determine if nursing interventions help prevent hospital
      acquired pressure ulcer (HAPU) development.

PMID- 24662547
TI  - Enlist, engage, and educate: transfer mobility teams to the rescue!
AB  - Would implementing these targeted groups in your organization help reduce HAPUs? 

PMID- 24662548
TI  - Decisions, decisions! E-portfolio as an effective hiring assessment tool.

PMID- 24662549
TI  - Mapping the future.

PMID- 24662550
TI  - Pituitary involvement in granulomatosis with polyangiitis.

PMID- 24662551
TI  - Efficacy and safety of anti-interleukin 6 receptor monoclonal antibody
      (tocilizumab) in Colombian patients with Takayasu arteritis.
AB  - PURPOSE: The aim of this study was to describe the efficacy and safety of anti
      interleukin 6 receptor antibody (tocilizumab [TCZ]) in patients with severe or
      refractory Takayasu arteritis (TA). METHODS: We describe 8 Colombian patients
      with severe and/or refractory TA treated with TCZ during a period of at least 9
      months. Clinical, radiological, biological, and associated treatments were
      evaluated before, during, and after TCZ infusions. RESULTS: The median age at
      evaluation was 31 years (12-43 years). All patients were female and experienced
      clinical and biological improvement, in addition to a corticosteroid-sparing
      effect from a median dose of 50 mg/d at baseline (30-60 mg/d) to 6.25 mg/d (2.5
      10 mg/d) at 9 months. In 4 cases, in which imaging studies were available, an
      improvement was observed. The median duration of TCZ infusions was 18 months (9
      36 months). Major adverse effects related to TCZ were not evidenced during a
      period of at least 9 months of treatment. One relapse was observed. Tocilizumab
      was continued in all cases until the last follow-up. CONCLUSIONS: This study
      shows a clinical, biological, and radiological response in patients with
      refractory TA treated with TCZ.

PMID- 24662552
TI  - Serum transaminases are frequently elevated at time of diagnosis of idiopathic
      inflammatory myopathy and normalize with creatine kinase.
AB  - INTRODUCTION: Despite multiple reports of elevated transaminases in muscle
      injury, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are
      not always considered indicators of muscle damage. The purpose of this study was
      to examine the relationship between serum AST, ALT, and creatine kinase (CK)
      levels at time of diagnosis of idiopathic inflammatory myopathy (IIM) and at the
      time of CK normalization. METHODS: We conducted a retrospective chart review of
      all adult patients attending rheumatology clinics at a county hospital with a
      diagnosis of IIM. Data collected included patient demographics, serial CK
      measurements, and serial serum transaminase measurements. RESULTS: We identified
      85 patients with IIM. At myositis presentation, 75 (88%) had CK above the upper
      limit of normal (ULN), 72 (85%) had AST above the ULN, and 68 (80%) had ALT above
      the ULN. The average CK was 5302 U/L (range, 23-38,461 U/L [SD, 7096]), average
      AST 215 U/L (range, 16-1270 [SD, 227]), and average ALT 137 U/L (range, 10-621
      [SD, 137]). The average AST and ALT at first available normalized CK was 26 U/L
      (range, 9-139 [SD, 18]) and 26 U/L (range, 5-96 [SD, 19]). We found a strong
      correlation between CK and AST (r= 0.832; P < 0.001) and ALT (r = 0.775; P <
      0.001) at initial presentation and also at the time of peak CK levels (r = 0.874
      [P < 0.001] and r = 0.842 [P < 0.001], respectively). CONCLUSIONS: In our series,
      we found a strong correlation between CK and serum transaminases. Serum
      transaminases were elevated in 80% of patients at the time of presentation and
      normalized in 85% of the patients at the time of CK normalization. Appropriate
      recognition of these laboratory changes in IIM may help reduce unnecessary
      hepatic evaluation, delayed diagnosis, unnecessary avoidance of second line
      immunosuppressants, and misdiagnosis of primary liver disease.

PMID- 24662553
TI  - Physical functioning in patients with ankylosing spondylitis: comparing
      approaches of experienced ability with self-reported and objectively measured
      physical activity.
AB  - BACKGROUND: Physical functioning can be assessed by different approaches that are
      characterized by increasing levels of individual appraisal. There is insufficient
      insight into which approach is the most informative in patients with ankylosing
      spondylitis (AS) compared with control subjects. OBJECTIVE: The objective of this
      study was to compare patients with AS and control subjects regarding 3 approaches
      of functioning: experienced ability to perform activities (Bath Ankylosing
      Spondylitis Functional Index [BASFI]), self-reported amount of physical activity
      (PA) (Baecke questionnaire), and the objectively measured amount of PA (triaxial
      accelerometer). METHODS: This case-control study included 24 AS patients and 24
      control subjects (matched for age, gender, and body mass index). Subjects
      completed the BASFI and Baecke questionnaire and wore a triaxial accelerometer.
      Subjects also completed other self-reported measures on disease activity (Bath AS
      Disease Activity Index), fatigue (Multidimensional Fatigue Inventory), and
      overall health (EuroQol visual analog scale). RESULTS: Both groups included 14
      men (58%), and the mean age was 48 years. Patients scored significantly worse on
      the BASFI (3.9 vs 0.2) than their healthy peers, whereas PA assessed by Baecke
      and the accelerometer did not differ between groups. Correlations between
      approaches of physical functioning were low to moderate. Bath Ankylosing
      Spondylitis Functional Index was associated with disease activity (r = 0.49) and
      physical fatigue (0.73) and Baecke with physical and activity related fatigue (r
      = 0.54 and r = 0.54), but total PA assessed by accelerometer was not associated
      with any of these experience-based health outcomes. CONCLUSIONS: Different
      approaches of the concept physical functioning in patients with AS provide
      different information. Compared with matched control subjects, patients with AS
      report more difficulties but report and objectively perform the same amount of
      PA.

PMID- 24662554
TI  - Concerns of patients with gout are incompletely captured by OMERACT-endorsed
      domains of measurement for chronic gout studies.
AB  - BACKGROUND: Appropriate evaluation of disease or treatment outcomes requires a
      good understanding of the aspects of the disease and its consequences that
      actually matter to patients. The OMERACT process has identified several domains
      of outcome measurement for chronic gout, but patient involvement has only been
      briefly described. OBJECTIVES: To make the results of patient involvement more
      explicit, the current study reports on an exercise carried out in the early part
      of the OMERACT domain identification process. METHODS: Patients with gout were
      asked to identify areas of life affected by gout. These areas were rated (0-10)
      and ranked for importance by a second group of patients with gout recruited from
      both primary care and a rheumatology clinic. RESULTS: Thirty-one patients with
      gout performed the initial generation of areas of importance. These areas were
      combined to form 14 items, which were ranked and scored by 107 patients. Four
      areas were ranked first to third most important by at least 20% of participants.
      These were pain (median rating, 10), loss of joint motion (median rating, 9),
      work loss (median rating, 7), and joint inflammation/swelling (median rating, 8).
      Three additional areas were ranked highly by at least 10% of patients: difficulty
      with wearing shoes, having to undertake a restrictive diet, and sleep.
      CONCLUSIONS: These data largely confirmed the relevance of the gout OMERACT
      domains while identifying additional issues for patients that require further
      investigation.

PMID- 24662555
TI  - Insights into uveitis in association with spondyloarthritis from a large patient
      survey.
AB  - BACKGROUND: Uveitis is reported to be the most common extra-articular feature in
      spondyloarthritis (SpA). OBJECTIVE: The objective of this study was to
      investigate the relationship between uveitis and SpA in a cohort identified from
      a survey. METHODS: Eight hundred sixty-three respondents completed a survey
      conducted by the Spondylitis Association of America. Data on baseline
      demographics, quality of life, medication use, and joint involvement were
      compared in SpA patients with and without uveitis. Logistic regression analysis
      was used to identify characteristics associated with the presence of uveitis.
      RESULTS: Of the 863 respondents, 168 (19.5%) reported a diagnosis of uveitis.
      Baseline demographics including sex, age, and ethnicity were similar between the
      uveitis and no-uveitis groups. The presence of uveitis had a significant positive
      association with the use of the biologic drug infliximab (adjusted odds ratio
      [ORadj] = 1.66, P = 0.044), "lower jaw" involvement (ORadj = 1.60, P = 0.015),
      heel involvement (ORadj = 1.51, P = 0.023), and a diagnosis of arthritis
      associated with inflammatory bowel disease (ORadj = 1.92, P = 0.005). It had a
      significant negative association with the use of the biologic drug etanercept
      (ORadj = 0.49, P = 0.011) or a coexisting diagnosis of diabetes (ORadj = 0.02, P
      = 0.020). CONCLUSIONS: The relationship of uveitis to medication presumably
      reflects the choice of a specific tumor necrosis factor inhibitor in the setting
      of a history of uveitis. One prior study has also correlated heel pain and
      uveitis, thus supporting the validity of the association and suggesting
      potentially a common pathogenesis. Because diabetes has been proposed as a risk
      factor for uveitis, the negative association is surprising and may distinguish
      the pathogenesis of uveitis in association with SpA from other forms of uveitis.

PMID- 24662556
TI  - Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome,
      irritable bowel syndrome, and interstitial cystitis: a review of case-control
      studies.
AB  - BACKGROUND: Fibromyalgia often coexists and overlaps with other syndromes such as
      chronic fatigue, irritable bowel syndrome, and interstitial cystitis. Chronic
      stress has been implicated in the pathogenesis of these illnesses. The
      sympathetic nervous system is a key element of the stress response system.
      Sympathetic dysfunction has been reported in these syndromes, raising the
      possibility that such dysautonomia could be their common clustering underlying
      pathogenesis. OBJECTIVE: The objective of this study was to carry out a review of
      all published comparative case-control studies investigating sympathetic nervous
      system performance in fibromyalgia, chronic fatigue syndrome, irritable bowel
      syndrome, and interstitial cystitis. METHODS: Online databases PubMed and EMBASE
      were accessed using the following key words: autonomic (OR) sympathetic (AND)
      fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and
      interstitial cystitis. All entries up to December 10th 2012 were reviewed by 2
      independent investigators searching for case-control studies in humans. The
      Method for Evaluating Research and Guidelines Evidence adapted to the Scottish
      Intercollegiate Guidelines Network was used to rank the level of evidence
      contained in the selected articles. RESULTS: A total of 196 articles are included
      in this review. The most often used methods to assess sympathetic functionality
      were heart rate variability analysis, sympathetic skin response, tilt table
      testing, and genetic studies. The majority of studies (65%) described sympathetic
      nervous system predominance in these overlapping syndromes. In contrast, 7% of
      the studies found parasympathetic predominance. CONCLUSIONS: This review
      demonstrates that sympathetic nervous system predominance is common in
      fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and
      interstitial cystitis. This concordance raises the possibility that sympathetic
      dysfunction could be their common underlying pathogenesis that brings on
      overlapping clinical features. The recognition of sympathetic predominance in
      these 4 syndromes may have potential clinical implications. It may be worth
      exploring the use of nonpharmacological measures as well as drug therapies aimed
      to regain autonomic balance.

PMID- 24662557
TI  - Central diabetes insipidus as the presenting symptom of granulomatosis with
      polyangiitis.
AB  - Granulomatosis with polyangiitis (Wegener's; GPA) is a necrotizing granulomatous
      vasculitis that can affect any organ system; however, central nervous system
      involvement is uncommon. We present 2 cases where central diabetes insipidus was
      the presenting manifestation of GPA. Pituitary involvement was documented by
      magnetic resonance imaging. Both patients were female and responded to
      combination therapy of prednisone and cyclophosphamide. We also review the
      literature for all reported cases of pituitary involvement in GPA. We conclude
      that pituitary involvement in GPA seems more common in females and may be the
      initial presenting clinical feature and may occur in the absence of systemic
      disease. Early recognition and treatment may prevent pituitary necrosis and
      irreversible damage. 

PMID- 24662558
TI  - Upper-extremity digital ischemia in granulomatosis with polyangiitis.
AB  - We report a case of granulomatosis with polyangiitis (GPA) in a 48-year-old man
      that was complicated by upper-extremity digital ischemia. Our patient initially
      presented with acute kidney injury, nasal and sinus symptoms, and bilateral lower
      extremity swelling. He was diagnosed with GPA based on clinical features,
      findings on renal biopsy, and positive antineutrophilic cytoplasmic antibodies.
      He was treated with immunosuppression, but during the course of the disease, he
      developed cyanosis in his bilateral upper extremities. In our case, middle-/large
      size arteries (Chapel Hill Consensus Conference nomenclature) in the upper
      extremities were occluded, and this caused the digital ischemia. Despite
      treatment with immunosuppression, plasmapheresis, and antithrombotic therapy, our
      patient's digital ischemia progressed leading to autoamputation of his fingers.
      Because of the rarity of digital ischemia in GPA, this case presented with many
      diagnostic and therapeutic challenges. 

PMID- 24662559
TI  - Nasu-Hakola disease as suspected cause for bone disease and dementia.
AB  - Progressive dementia in conjunction with multiple bone fractures in a previously
      healthy young man led to the investigation of the underlying cause. The
      differential diagnoses (most importantly hypoparathyroidism) were limited given
      basal ganglia calcifications on the brain computed tomographic scan. Electronic
      search of the key words basal ganglia calcification, osteoporosis, and dementia
      revealed a rare condition termed Nasu-Hakola disease or polycystic lipomembranous
      osteodysplasia with sclerosing leukoencephalopathy. This very rare and
      potentially fatal genetic disease is characterized by pathological fractures,
      multiple lytic bone lesions, and presenile dementia. We report an Iranian patient
      with this disease and a review of the literature. 

PMID- 24662560
TI  - Nonvasculitic autoimmune meningoencephalitis after rituximab: the potential
      downside of depleting regulatory B cells in the brain.
AB  - Nonvasculitic autoimmune meningoencephalitis (NAIM) is a rare condition
      describing a syndrome of steroid-responsive encephalopathy in patients with
      similar clinical and pathologic features. It can be associated with autoimmune
      diseases, such as Sjogren's syndrome and autoimmune thyroiditis. Brain biopsies
      usually show inflammatory cells without evidence of vasculitis. In this article,
      we present a patient who developed NAIM after receiving rituximab, a B-cell
      depleting therapy for rheumatoid arthritis. The brain biopsy showed a lack of B
      lymphocytes in the brain tissue, and the patient responded well to intravenous
      immunoglobulins. We further discuss the role of B lymphocytes and specific
      regulatory B lymphocytes in suppressing autoimmunity in the brain and propose
      that the depletion of regulatory B cells may contribute to the pathogenesis of
      NAIM. This case illustrates a potential side effect of rituximab and demonstrates
      the importance of regulatory B cells in maintaining the immune response. 

PMID- 24662561
TI  - Systemic lupus erythematosus presenting as Stevens-Johnson syndrome/toxic
      epidermal necrolysis.
AB  - Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)-like lesions in
      acute cutaneous lupus erythematosus [LE]) are an unusual manifestation of
      systemic LE. We describe a patient with widespread vesiculobullous lesions
      diagnosed as SJS/TEN-like acute cutaneous LE as the initial presentation of
      systemic LE. Stevens-Johnson syndrome/TEN-like LE may be differentiated from
      other vesiculobullous lesions by factors including a history of recent LE
      exacerbation, photodistribution of lesions, lack of a precipitating infection or
      medication exposure, minimal mucosal involvement, a prolonged course, response
      steroid treatment, and histologic and immunofluorescence findings. It is
      paramount to identify SJS/TEN-like LE as this condition requires early and
      aggressive intervention. The optimal treatment approach for SJS/TEN-like LE is
      unclear, and although some case reports have shown glucocorticoids to be useful,
      there are also reports of cases in which additional measures, such as intravenous
      immunoglobulin and plasmapheresis, were required to achieve a response. Our
      patient's condition was refractory to high-dose corticosteroids and intravenous
      immunoglobulin but was successfully treated using plasma exchange. As such, this
      treatment may hold potential for improving the care of other patients with
      refractory SJS/TEN-like LE. 

PMID- 24662562
TI  - Challenges faced by patients in gout treatment: a qualitative study.

PMID- 24662563
TI  - Retroperitoneal fibrosis in IgG4-related disease.

PMID- 24662564
TI  - Retrograde neurotrophin signaling through Tollo regulates synaptic growth in
      Drosophila.
AB  - Toll-like receptors (TLRs) are best characterized for their roles in mediating
      dorsoventral patterning and the innate immune response. However, recent studies
      indicate that TLRs are also involved in regulating neuronal growth and
      development. Here, we demonstrate that the TLR Tollo positively regulates growth
      of the Drosophila melanogaster larval neuromuscular junction (NMJ). Tollo mutants
      exhibited NMJ undergrowth, whereas increased expression of Tollo led to NMJ
      overgrowth. Tollo expression in the motoneuron was both necessary and sufficient
      for regulating NMJ growth. Dominant genetic interactions together with altered
      levels of phosphorylated c-Jun N-terminal kinase (JNK) and puc-lacZ expression
      revealed that Tollo signals through the JNK pathway at the NMJ. Genetic
      interactions also revealed that the neurotrophin Spatzle3 (Spz3) is a likely
      Tollo ligand. Spz3 expression in muscle and proteolytic activation via the Easter
      protease was necessary and sufficient to promote NMJ growth. These results
      demonstrate the existence of a novel neurotrophin signaling pathway that is
      required for synaptic development in Drosophila. 

PMID- 24662565
TI  - p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell
      invasion.
AB  - Oncogenic Ras induces cell transformation and promotes an invasive phenotype. The
      tumor suppressor p53 has a suppressive role in Ras-driven invasion. However, its
      mechanism remains poorly understood. Here we show that p53 induces activation of
      the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as
      Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton.
      Oncogenic Ras increases accumulation of p53 in the cytoplasm, which promotes the
      translocation of p38 mitogen-activated protein kinase (MAPK) into mitochondria
      and induces phosphorylation of HtrA2/Omi. Concurrently, oncogenic Ras also
      induces mitochondrial fragmentation, irrespective of p53 expression, causing the
      release of HtrA2/Omi from mitochondria into the cytosol. Phosphorylated HtrA2/Omi
      therefore cleaves beta-actin and decreases the amount of filamentous actin (F
      actin) in the cytosol. This ultimately down-regulates p130 Crk-associated
      substrate (p130Cas)-mediated lamellipodia formation, countering the invasive
      phenotype initiated by oncogenic Ras. Our novel findings provide insights into
      the mechanism by which p53 prevents the malignant progression of transformed
      cells. 

PMID- 24662566
TI  - Dynamin photoinactivation blocks Clathrin and alpha-adaptin recruitment and
      induces bulk membrane retrieval.
AB  - Dynamin is a well-known regulator of synaptic endocytosis. Temperature-sensitive
      dynamin (shi(ts1)) mutations in Drosophila melanogaster or deletion of some of
      the mammalian Dynamins causes the accumulation of invaginated endocytic pits at
      synapses, sometimes also on bulk endosomes, indicating impaired membrane
      scission. However, complete loss of dynamin function has not been studied in
      neurons in vivo, and whether Dynamin acts in different aspects of synaptic
      vesicle formation remains enigmatic. We used acute photoinactivation and found
      that loss of Dynamin function blocked membrane recycling and caused the buildup
      of huge membrane-connected cisternae, in contrast to the invaginated pits that
      accumulate in shi(ts1) mutants. Moreover, photoinactivation of Dynamin in
      shi(ts1) animals converted these pits into bulk cisternae. Bulk membrane
      retrieval has also been seen upon Clathrin photoinactivation, and superresolution
      imaging indicated that acute Dynamin photoinactivation blocked Clathrin and alpha
      adaptin relocalization to synaptic membranes upon nerve stimulation. Hence, our
      data indicate that Dynamin is critically involved in the stabilization of
      Clathrin- and AP2-dependent endocytic pits. 

PMID- 24662567
TI  - SUN proteins facilitate the removal of membranes from chromatin during nuclear
      envelope breakdown.
AB  - SUN proteins reside in the inner nuclear membrane and form complexes with KASH
      proteins of the outer nuclear membrane that connect the nuclear envelope (NE) to
      the cytoskeleton. These complexes have well-established functions in nuclear
      anchorage and migration in interphase, but little is known about their
      involvement in mitotic processes. Our analysis demonstrates that simultaneous
      depletion of human SUN1 and SUN2 delayed removal of membranes from chromatin
      during NE breakdown (NEBD) and impaired the formation of prophase NE
      invaginations (PNEIs), similar to microtubule depolymerization or down-regulation
      of the dynein cofactors NudE/EL. In addition, overexpression of dominant-negative
      SUN and KASH constructs reduced the occurrence of PNEI, indicating a requirement
      for functional SUN-KASH complexes in NE remodeling. Codepletion of SUN1/2 slowed
      cell proliferation and resulted in an accumulation of morphologically defective
      and disoriented mitotic spindles. Quantification of mitotic timing revealed a
      delay between NEBD and chromatin separation, indicating a role of SUN proteins in
      bipolar spindle assembly and mitotic progression. 

PMID- 24662568
TI  - ADF/cofilin promotes invadopodial membrane recycling during cell invasion in
      vivo.
AB  - Invadopodia are protrusive, F-actin-driven membrane structures that are thought
      to mediate basement membrane transmigration during development and tumor
      dissemination. An understanding of the mechanisms regulating invadopodia has been
      hindered by the difficulty of examining these dynamic structures in native
      environments. Using an RNAi screen and live-cell imaging of anchor cell (AC)
      invasion in Caenorhabditis elegans, we have identified UNC-60A (ADF/cofilin) as
      an essential regulator of invadopodia. UNC-60A localizes to AC invadopodia, and
      its loss resulted in a dramatic slowing of F-actin dynamics and an inability to
      breach basement membrane. Optical highlighting indicated that UNC-60A
      disassembles actin filaments at invadopodia. Surprisingly, loss of unc-60a led to
      the accumulation of invadopodial membrane and associated components within the
      endolysosomal compartment. Photobleaching experiments revealed that during normal
      invasion the invadopodial membrane undergoes rapid recycling through the
      endolysosome. Together, these results identify the invadopodial membrane as a
      specialized compartment whose recycling to form dynamic, functional invadopodia
      is dependent on localized F-actin disassembly by ADF/cofilin. 

PMID- 24662569
TI  - TAp73 is essential for germ cell adhesion and maturation in testis.
AB  - A core evolutionary function of the p53 family is to protect the genomic
      integrity of gametes. However, the role of p73 in the male germ line is unknown.
      Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation
      factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73
      knockout (TAp73KO) and p73KO mice, but not DeltaNp73KO mice, display a "near
      empty seminiferous tubule" phenotype due to massive premature loss of immature
      germ cells. The cellular basis of this phenotype is defective cell-cell adhesions
      of developing germ cells to Sertoli nurse cells, with likely secondary
      degeneration of Sertoli cells, including the blood-testis barrier, which leads to
      disruption of the adhesive integrity and maturation of the germ epithelium. At
      the molecular level, TAp73, which is produced in germ cells, controls a
      coordinated transcriptional program of adhesion- and migration-related proteins
      including peptidase inhibitors, proteases, receptors, and integrins required for
      germ-Sertoli cell adhesion and dynamic junctional restructuring. Thus, we propose
      the testis as a unique organ with strict division of labor among all family
      members: p63 and p53 safeguard germ line fidelity, whereas TAp73 ensures
      fertility by enabling sperm maturation. 

PMID- 24662570
TI  - Influence of aerobic training and detraining on serum BDNF, insulin resistance,
      and metabolic risk factors in middle-aged men diagnosed with metabolic syndrome.
AB  - OBJECTIVE: To study the influence of aerobic exercise training on brain-derived
      neurotrophic factor (BDNF), insulin resistance, and lipid profile in middle-aged
      men diagnosed with metabolic syndrome (MetS). DESIGN: This is an experimental
      repeated measure study. SETTING: Subjects participated in aerobic training
      programs (18 sessions of 25-40 minutes per session) in Guilan University
      gymnasium and court. PARTICIPANTS: A total of 21 middle-aged men (50-65 years
      old) diagnosed with MetS participated. INTERVENTIONS: We randomly divided 21
      middle-aged men with MetS into exercise and control groups. The exercise group
      followed an aerobic training program (18 sessions, 3/wk) at 50% to 60% of
      V[Combining Dot Above]O2 peak (25-40 minutes per session) and 6 weeks of
      detraining. Blood samples were collected at baseline, end of the training, and
      detraining. MAIN OUTCOME MEASURES: High BDNF level in patients with MetS and its
      reduction after chronic aerobic exercise. RESULTS: Aerobic training significantly
      decreased all the metabolic risk factors, including overall MetS z score, insulin
      resistance, and lipid profile (P < 0.05). After the detraining period, plasma
      triglyceride, high-density lipoprotein, and also overall MetS z score remained
      unchanged (P < 0.05); however, serum BDNF, which was decreased by aerobic
      training (P = 0.013), restored to the baseline at the end of the detraining (P =
      0.018). CONCLUSIONS: Improved metabolic risk factors along with decreased serum
      BDNF in response to aerobic training and the opposite direction during the
      detraining emphasize the importance of physical activity in the treatment of MetS
      and prevention of related diseases.

PMID- 24662571
TI  - Dysbaric osteonecrosis: a literature review of pathophysiology, clinical
      presentation, and management.
AB  - OBJECTIVE: To perform a general literature review of dysbaric osteonecrosis (DON)
      to describe its pathophysiology, prevalence in scuba divers, prognosis, and
      treatment options. DATA SOURCES: A literature search on PubMed was performed
      using the term "dysbaric osteonecrosis" yielding 67 results. There was no
      exclusion based on dates. Articles that mainly dealt with decompression sickness
      secondary to tunnel work, mining, or airplane travel were not selected. An
      additional search on PubMed using the terms "(osteonecrosis diving) NOT dysbaric"
      was performed to identify other publications not picked up in the initial search.
      MAIN RESULTS: Dysbaric osteonecrosis is associated with prolonged hyperbaric
      exposure and rapid decompression that cause nitrogen bubbles to enter the fatty
      marrow-containing shafts of long bones leading to reduction in blood flow and
      subsequent osteonecrosis. Patients may present asymptomatically, and typical
      radiographic findings of DON include: decalcification of bone, cystic lesions,
      osteosclerotic patterns, nontraumatic fractures, bone islands, and a subchondral
      crescent sign. Surgical treatment options are comprised of core decompression and
      free vascularized fibular graft, whereas nonsurgical treatment options consist of
      monitoring, physical therapy, and bisphosphonate therapy. CONCLUSIONS: Although
      the incidence of DON has decreased significantly over the past 2 decades, the
      lack of timely diagnosis and optimal management keeps DON relevant in the
      orthopedic and sport medicine community.

PMID- 24662572
TI  - Core stability exercises for low back pain in athletes: a systematic review of
      the literature.
AB  - OBJECTIVE: The aim of this study was to systematically review the evidence for
      the effectiveness of core stability exercises for treating athletes with low back
      pain (LBP). DATA SOURCES: We searched several databases (Medline, AMED, CINAHL,
      SportDiscus, and EMBASE). Our eligibility criteria consisted of articles
      published in a peer-reviewed journal in English, using any prospective clinical
      study design, where athletes with nonspecific LBP were treated with core
      stability exercises in at least 1 study arm, and back pain intensity and/or
      disability were used as outcome measures. All included randomized controlled
      trials (RCTs) were assessed for risk of bias using the Cochrane Risk of Bias
      tool, whereas non-RCT studies were assessed for quality using the Downs and Black
      checklist. MAIN RESULTS: Five studies including 151 participants met the
      inclusion criteria, including 2 RCTs. The quality of the literature on this topic
      was deemed to be low overall, with only 1 non-RCT having a moderate quality
      score, and 1 RCT having a lower risk of bias. Four studies reported statistically
      significant decreases in back pain intensity in their core stability intervention
      group. CONCLUSIONS: The quantity and quality of literature on the use of core
      stability exercises for treating LBP in athletes is low. The existing evidence
      has been conducted on small and heterogeneous study populations using
      interventions that vary drastically with only mixed results and short-term follow
      up. This precludes the formulation of strong conclusions, and additional high
      quality research is clearly needed.

PMID- 24662573
TI  - Surgical management of traumatic avulsion of the ischial tuberosity in young
      athletes.
AB  - OBJECTIVE: Complete traumatic avulsion of the ischial tuberosity in young
      athletes is rare, and the optimal treatment is unclear. The purpose of this
      article is to present our experience and the efficacy of surgical repair of
      avulsions of the ischial tuberosity with bony dislocation of more than 2 cm and
      to discuss the complex postoperative rehabilitation. METHODS: Three young
      athletes sustained complete avulsion of the ischial tuberosity with bony
      dislocation during different sport activities (long jump, soccer, sprinting). The
      age at the time of injury ranged from 13.8 to 15 years. All underwent surgical
      repair with reattachment of the hamstring muscle complex to the origin on the
      ischium. The time from injury to repair varied from 2 to 22 weeks. All patients
      underwent a specific postoperative rehabilitation program. Follow-up ranged from
      12 to 24 months. RESULTS: All athletes had improved with surgery and had good
      subjective and objective functional results. One patient needed operative
      revision 1 day after primary repair because of suture loosening because of
      excessive muscle contractions during wake up after general anesthesia. Finally,
      all returned to their preinjury sport at the same level. CONCLUSIONS: Young
      athletes with traumatic avulsion of the ischial tuberosity and dislocation of
      more than 2 cm benefit from operative repair. Good results were achieved in all
      cases on the basis of functional recovery and patient satisfaction. Chronic
      complaints could be avoided, and also return to sport was possible. Surgery under
      spinal anesthesia is recommended.

PMID- 24662575
TI  - Concurrent saturation transfer contrast in in vivo brain by a uniform
      magnetization transfer MRI.
AB  - The development of chemical exchange saturation transfer (CEST) and magnetization
      transfer (MT) contrast in MRI has enabled the enhanced detection of metabolites
      and biomarkers in vivo. In brain MRI, the separation between CEST and MT contrast
      has been particularly difficult due to overlaps in the frequency responses of the
      contrast mechanisms. We demonstrate here that MT and CEST contrast can be
      separated in the brain by the so-called uniform-MT (uMT) technique, thus opening
      the door to addressing long-standing ambiguities in this field. These methods
      could be useful for keeping track of important endogenous metabolites and for
      providing an improved understanding of neurological and neurodegenerative
      disorders. Examples are shown from white and gray matter regions in healthy
      volunteers and patients with multiple sclerosis, which demonstrated that the MT
      effects in the brain were asymmetric and that the uMT method could make them
      uniform. 

PMID- 24662574
TI  - Characterizing individual differences in functional connectivity using dual
      regression and seed-based approaches.
AB  - A central challenge for neuroscience lies in relating inter-individual
      variability to the functional properties of specific brain regions. Yet,
      considerable variability exists in the connectivity patterns between different
      brain areas, potentially producing reliable group differences. Using sex
      differences as a motivating example, we examined two separate resting-state
      datasets comprising a total of 188 human participants. Both datasets were
      decomposed into resting-state networks (RSNs) using a probabilistic spatial
      independent component analysis (ICA). We estimated voxel-wise functional
      connectivity with these networks using a dual-regression analysis, which
      characterizes the participant-level spatiotemporal dynamics of each network while
      controlling for (via multiple regression) the influence of other networks and
      sources of variability. We found that males and females exhibit distinct patterns
      of connectivity with multiple RSNs, including both visual and auditory networks
      and the right frontal-parietal network. These results replicated across both
      datasets and were not explained by differences in head motion, data quality,
      brain volume, cortisol levels, or testosterone levels. Importantly, we also
      demonstrate that dual-regression functional connectivity is better at detecting
      inter-individual variability than traditional seed-based functional connectivity
      approaches. Our findings characterize robust-yet frequently ignored-neural
      differences between males and females, pointing to the necessity of controlling
      for sex in neuroscience studies of individual differences. Moreover, our results
      highlight the importance of employing network-based models to study variability
      in functional connectivity. 

PMID- 24662576
TI  - Modular structure of functional networks in olfactory memory.
AB  - Graph theory enables the study of systems by describing those systems as a set of
      nodes and edges. Graph theory has been widely applied to characterize the overall
      structure of data sets in the social, technological, and biological sciences,
      including neuroscience. Modular structure decomposition enables the definition of
      sub-networks whose components are gathered in the same module and work together
      closely, while working weakly with components from other modules. This processing
      is of interest for studying memory, a cognitive process that is widely
      distributed. We propose a new method to identify modular structure in task
      related functional magnetic resonance imaging (fMRI) networks. The modular
      structure was obtained directly from correlation coefficients and thus retained
      information about both signs and weights. The method was applied to functional
      data acquired during a yes-no odor recognition memory task performed by young and
      elderly adults. Four response categories were explored: correct (Hit) and
      incorrect (False alarm, FA) recognition and correct and incorrect rejection. We
      extracted time series data for 36 areas as a function of response categories and
      age groups and calculated condition-based weighted correlation matrices. Overall,
      condition-based modular partitions were more homogeneous in young than elderly
      subjects. Using partition similarity-based statistics and a posteriori
      statistical analyses, we demonstrated that several areas, including the
      hippocampus, caudate nucleus, and anterior cingulate gyrus, belonged to the same
      module more frequently during Hit than during all other conditions. Modularity
      values were negatively correlated with memory scores in the Hit condition and
      positively correlated with bias scores (liberal/conservative attitude) in the Hit
      and FA conditions. We further demonstrated that the proportion of positive and
      negative links between areas of different modules (i.e., the proportion of
      correlated and anti-correlated areas) accounted for most of the observed
      differences in signed modularity. Taken together, our results provided some
      evidence that the neural networks involved in odor recognition memory are
      organized into modules and that these modular partitions are linked to behavioral
      performance and individual strategies. 

PMID- 24662577
TI  - EEG extended source localization: tensor-based vs. conventional methods.
AB  - The localization of brain sources based on EEG measurements is a topic that has
      attracted a lot of attention in the last decades and many different source
      localization algorithms have been proposed. However, their performance is limited
      in the case of several simultaneously active brain regions and low signal-to
      noise ratios. To overcome these problems, tensor-based preprocessing can be
      applied, which consists in constructing a space-time-frequency (STF) or space
      time-wave-vector (STWV) tensor and decomposing it using the Canonical Polyadic
      (CP) decomposition. In this paper, we present a new algorithm for the accurate
      localization of extended sources based on the results of the tensor
      decomposition. Furthermore, we conduct a detailed study of the tensor-based
      preprocessing methods, including an analysis of their theoretical foundation,
      their computational complexity, and their performance for realistic simulated
      data in comparison to conventional source localization algorithms such as
      sLORETA, cortical LORETA (cLORETA), and 4-ExSo-MUSIC. Our objective consists, on
      the one hand, in demonstrating the gain in performance that can be achieved by
      tensor-based preprocessing, and, on the other hand, in pointing out the limits
      and drawbacks of this method. Finally, we validate the STF and STWV techniques on
      real measurements to demonstrate their usefulness for practical applications. 

PMID- 24662578
TI  - Modulation of the N30 generators of the somatosensory evoked potentials by the
      mirror neuron system.
AB  - The N30 component of the somatosensory evoked potential is known to be modulated
      by sensory interference, motor action, movement ideation and observation. We
      introduce a new paradigm in which the observation task of another person's hand
      movement triggers the somatosensory stimulus, inducing the N30 response in
      participants. In order to identify the possible contribution of the mirror neuron
      network (MNN) to this early sensorimotor processing, we analyzed the N30
      topography, the event-related spectral perturbation and the inter-trial coherence
      on single electroencephalogram (EEG) trials, and we applied swLORETA to localize
      the N30 sources implicated in the time-frequency domain at rest and during
      observation, as well as the generators differentiating these two contextual brain
      states. We found that N30 amplitude increase correlated with increased
      contralateral precentral alpha, frontal beta, and contralateral frontal gamma
      power spectrum, and with central and precentral alpha and parietal beta phase
      locking of ongoing EEG signals. We demonstrate specific activation of the
      contralateral post-central and parietal cortex where the angular gyrus (BA39), an
      important MNN node, is implicated in this enhancement during observation. We
      conclude that this part of the MNN, involved in proprioceptive processing and
      more complex body-action representations, is already active prior to
      somatosensory input and may enhance N30. 

PMID- 24662580
TI  - Prefrontal mechanisms in preference and non-preference-based judgments.
AB  - When we decide between two options, we can make our decision based on what we
      prefer, (preference-based choice), or we can also choose based on which option we
      want to avoid more (non-preference-based choice). Most decision making research
      has examined preference-based choice but has not differentiated it from non
      preference-based choice. The decision making process can be decomposed into
      multiple value-based computational processes, which are shown to be subserved by
      different regions in the prefrontal cortex (PFC). Here we show that the same
      decision circuits within the PFC are configured differently depending on whether
      decisions are made based on preference or non-preference criteria (decision
      rule). Activation in the dorsolateral PFC changed depending on both the values of
      the two choice options and decision rule. We also found that activation in the
      medial and lateral PFC was modulated linearly according to the difference in
      value between the two items and according to the value of the chosen item,
      respectively. In the medial and lateral PFC, there were distinct patterns of
      activation between dorsal and ventral regions: in dorsal regions value-related
      changes in activation were modulated by the decision rule, whereas in ventral
      regions activation patterns were not modulated. We propose that preference and
      non-preference decision rules represented in the dorsal PFC differently configure
      decision processes, resulting in context-specific significance being attached to
      the choice values represented in the ventral PFC. 

PMID- 24662579
TI  - The development of human amygdala functional connectivity at rest from 4 to 23
      years: a cross-sectional study.
AB  - Functional connections (FC) between the amygdala and cortical and subcortical
      regions underlie a range of affective and cognitive processes. Despite the
      central role amygdala networks have in these functions, the normative
      developmental emergence of FC between the amygdala and the rest of the brain is
      still largely undefined. This study employed amygdala subregion maps and resting
      state functional magnetic resonance imaging to characterize the typical
      development of human amygdala FC from age 4 to 23years old (n=58). Amygdala FC
      with subcortical and limbic regions was largely stable across this developmental
      period. However, three cortical regions exhibited age-dependent changes in FC:
      amygdala FC with the medial prefrontal cortex (mPFC) increased with age, amygdala
      FC with a region including the insula and superior temporal sulcus decreased with
      age, and amygdala FC with a region encompassing the parahippocampal gyrus and
      posterior cingulate also decreased with age. The transition from childhood to
      adolescence (around age 10years) marked an important change-point in the nature
      of amygdala-cortical FC. We distinguished unique developmental patterns of
      coupling for three amygdala subregions and found particularly robust convergence
      of FC for all subregions with the mPFC. These findings suggest that there are
      extensive changes in amygdala-cortical functional connectivity that emerge
      between childhood and adolescence. 

PMID- 24662581
TI  - Left ventricular diastolic dysfunction: a new foe in the management of atrial
      fibrillation?

PMID- 24662582
TI  - Can CPAP prevent myocardial damage?

PMID- 24662583
TI  - Transcatheter aortic valve implantation with the CoreValve for the treatment of
      rheumatic aortic stenosis.

PMID- 24662584
TI  - A case of unusual looking prosthetic mitral valve thrombosis treated with low
      dose slow infusion tPA.

PMID- 24662585
TI  - Misleading aspect of left atrial appendage membrane: an incidental
      echocardiographic finding.

PMID- 24662586
TI  - Acute thrombosis of the left internal mammary artery graft 14 years after
      coronary bypass surgery.

PMID- 24662587
TI  - GGT as predictor of coronary collateral development in chronic coronary total
      occlusion.

PMID- 24662588
TI  - Infective endocarditis in Turkey: changing trends in epidemiology.

PMID- 24662589
TI  - Elevated mean pulmonary artery pressure in patients with mild-to-moderate mitral
      stenosis: a useful predictor of worsening renal functions?

PMID- 24662590
TI  - Aggregation of lipoprotein(a) to apolipoprotein A-I and coronary artery problem.

PMID- 24662591
TI  - The relationship between mean platelet volume and high on-treatment platelet
      reactivity.

PMID- 24662592
TI  - Factors influencing the use of ambulance among patients with acute coronary
      syndrome: results of two centers in Turkey.

PMID- 24662593
TI  - Radiation safety awareness and practice among Iranian cardiology and radiology
      residents/fellows.

PMID- 24662594
TI  - Monocuspidalisation of the mitral valve can be a solution for ischemic mitral
      regurgitation.

PMID- 24662595
TI  - Partial detachment of the mitral valvular ring: importance of three- dimensional
      transesophageal echocardiography.

PMID- 24662596
TI  - An excellent collateralization between left internal mammary artery to left
      external iliac artery.

PMID- 24662597
TI  - Left atrial compression.

PMID- 24662598
TI  - Complete protection against aflatoxin B(1)-induced liver cancer with a
      triterpenoid: DNA adduct dosimetry, molecular signature, and genotoxicity
      threshold.
AB  - In experimental animals and humans, aflatoxin B1 (AFB1) is a potent hepatic toxin
      and carcinogen. The synthetic oleanane triterpenoid 1-[2-cyano-3-,12-dioxooleana
      1,9(11)-dien-28-oyl]imidazole (CDDO-Im), a powerful activator of Keap1-Nrf2
      signaling, protects against AFB1-induced toxicity and preneoplastic lesion
      formation (GST-P-positive foci). This study assessed and mechanistically
      characterized the chemoprotective efficacy of CDDO-Im against AFB1-induced
      hepatocellular carcinoma (HCC). A lifetime cancer bioassay was undertaken in F344
      rats dosed with AFB1 (200 MUg/kg rat/day) for four weeks and receiving either
      vehicle or CDDO-Im (three times weekly), one week before and throughout the
      exposure period. Weekly, 24-hour urine samples were collected for analysis of
      AFB1 metabolites. In a subset of rats, livers were analyzed for GST-P foci. The
      comparative response of a toxicogenomic RNA expression signature for AFB1 was
      examined. CDDO-Im completely protected (0/20) against AFB1-induced liver cancer
      compared with a 96% incidence (22/23) observed in the AFB1 group. With CDDO-Im
      treatment, integrated level of urinary AFB1-N(7)-guanine was significantly
      reduced (66%) and aflatoxin-N-acetylcysteine, a detoxication product, was
      consistently elevated (300%) after the first AFB1 dose. In AFB1-treated rats, the
      hepatic burden of GST-P-positive foci increased substantially (0%-13.8%) over the
      four weeks, but was largely absent with CDDO-Im intervention. The toxicogenomic
      RNA expression signature characteristic of AFB1 was absent in the AFB1 + CDDO-Im
      treated rats. The remarkable efficacy of CDDO-Im as an anticarcinogen is
      established even in the face of a significant aflatoxin adduct burden.
      Consequently, the absence of cancer requires a concept of a threshold for DNA
      damage for cancer development.

PMID- 24662600
TI  - Serotonin induces depolarization in lateral amygdala neurons by activation of
      TRPC-like current and inhibition of GIRK current depending on 5-HT(2C) receptor.
AB  - Regional differences are known in the serotonin-induced modulation of neuronal
      activity within the amygdala. This in vitro study in rats focuses on analyzing
      the ionic mechanism underlying serotonin-induced depolarization in the lateral
      amygdala. Serotonin depolarized membrane potential by 5 mV, which is underlain by
      a serotonin-induced inward current at rest with a characteristic reversal
      potential of -105 mV. From pharmacological experiments, the 5-HT2C subtype was
      singled out as the receptor subtype involved. Under blockade of K(+) channels by
      Ba(2+), 5-HT induced an inward current with no reversal at the range between -50
      and -130 mV, which was identified as a TRPC-like current. This current was
      blocked by the specific phosphatidylinositol 3-kinse (PI3-kinase) inhibitor
      LY294002, pointing to its dependence on PI3-kinase. The Ba(2+)-sensitive
      component, obtained by subtraction, showed a strong outward rectification and the
      reversal potential of K(+), indicating that this component results from a
      serotonin-induced inhibition of G-protein coupled inwardly rectifying K(+)
      channel (GIRK) current. By wortmannin, an inhibitor of both PI3-kinase and PI4
      kinase, a serotonin-induced phosphatidylinositol 4,5-bisphosphate (PIP2)
      depletion was revealed to underlie GIRK inhibition. Thus, the serotonin-induced
      current turned out to be caused by a combined occurrence of GIRK inhibition and
      PI3-kinase-dependent TRPC-like current. With serotonergic modulation, all these
      mechanisms should be recruited in lateral amygdala principal neurons and likely
      contribute to generation of region-specific neuronal activity patterns within the
      amygdala, which may at least partly implement its required role in fear and
      anxiety.

PMID- 24662601
TI  - Role of 6-shogaol in tert -butyl hydroperoxide-induced apoptosis of HepG2 cells.
AB  - The aim of this study was to investigate the protective effects of 6-shogaol on
      tert-butyl hydroperoxide (tBHP)-induced oxidative stress leading to apoptosis in
      human hepatoma cell line HepG2. The cells were exposed to tBHP (100 MUmol/l)
      after pretreatment with 6-shogaol (2.5 and 5 MUmol/l), and then cell viability
      was measured. 6-Shogaol fully prevented HepG2 cell death caused by tBHP.
      Treatment of tBHP resulted in apoptotic cell death as assessed by TUNEL assay and
      the expression of apoptosis regulator proteins, Bcl-2 family, caspases and
      cytochrome c. Cells treated with 6-shogaol showed rapid reduction of apoptosis by
      restoring these markers of apoptotic cells. In addition, 6-shogaol significantly
      recovered disruption of mitochondrial membrane potential as a start sign of
      hepatic apoptosis induced by oxidative stress. In line with this observation,
      antioxidative 6-shogaol inhibited generation of reactive oxygen species and
      depletion of reduced glutathione in tBHP-stimulated HepG2 cells. Taken together,
      these results for the first time showed antioxidative and antiapoptotic
      activities of 6-shogaol in tBHP-treated hepatoma HepG2 cells, suggesting that 6
      shogaol could be beneficial in hepatic disorders caused by oxidative stress.

PMID- 24662599
TI  - Predicting abuse potential of stimulants and other dopaminergic drugs: overview
      and recommendations.
AB  - Examination of a drug's abuse potential at multiple levels of analysis
      (molecular/cellular action, whole-organism behavior, epidemiological data) is an
      essential component to regulating controlled substances under the Controlled
      Substances Act (CSA). We reviewed studies that examined several central nervous
      system (CNS) stimulants, focusing on those with primarily dopaminergic actions,
      in drug self-administration, drug discrimination, and physical dependence. For
      drug self-administration and drug discrimination, we distinguished between
      experiments conducted with rats and nonhuman primates (NHP) to highlight the
      common and unique attributes of each model in the assessment of abuse potential.
      Our review of drug self-administration studies suggests that this procedure is
      important in predicting abuse potential of dopaminergic compounds, but there were
      many false positives. We recommended that tests to determine how reinforcing a
      drug is relative to a known drug of abuse may be more predictive of abuse
      potential than tests that yield a binary, yes-or-no classification. Several false
      positives also occurred with drug discrimination. With this procedure, we
      recommended that future research follow a standard decision-tree approach that
      may require examining the drug being tested for abuse potential as the training
      stimulus. This approach would also allow several known drugs of abuse to be
      tested for substitution, and this may reduce false positives. Finally, we
      reviewed evidence of physical dependence with stimulants and discussed the
      feasibility of modeling these phenomena in nonhuman animals in a rational and
      practical fashion. This article is part of the Special Issue entitled 'CNS
      Stimulants'. 

PMID- 24662602
TI  - A genetic and computational approach to structurally classify neuronal types.
AB  - The importance of cell types in understanding brain function is widely
      appreciated but only a tiny fraction of neuronal diversity has been catalogued.
      Here we exploit recent progress in genetic definition of cell types in an
      objective structural approach to neuronal classification. The approach is based
      on highly accurate quantification of dendritic arbor position relative to
      neurites of other cells. We test the method on a population of 363 mouse retinal
      ganglion cells. For each cell, we determine the spatial distribution of the
      dendritic arbors, or arbor density, with reference to arbors of an abundant, well
      defined interneuronal type. The arbor densities are sorted into a number of
      clusters that is set by comparison with several molecularly defined cell types.
      The algorithm reproduces the genetic classes that are pure types, and detects six
      newly clustered cell types that await genetic definition. 

PMID- 24662603
TI  - Evaluating effects of developmental education for college students using a
      regression discontinuity design.
AB  - BACKGROUND: Annually, American colleges and universities provide developmental
      education (DE) to millions of underprepared students; however, evaluation
      estimates of DE benefits have been mixed. OBJECTIVES: Using a prototypic exemplar
      of DE, our primary objective was to investigate the utility of a replicative
      evaluative framework for assessing program effectiveness. RESEARCH DESIGN: Within
      the context of the regression discontinuity (RD) design, this research examined
      the effectiveness of a DE program for five, sequential cohorts of first-time
      college students. Discontinuity estimates were generated for individual terms and
      cumulatively, across terms. SUBJECTS: Participants were 3,589 first-time
      community college students. MEASURES: DE program effects were measured by
      contrasting both college-level English grades and a dichotomous measure of
      pass/fail, for DE and non-DE students. RESULTS: Parametric and nonparametric
      estimates of overall effect were positive for continuous and dichotomous measures
      of achievement (grade and pass/fail). The variability of program effects over
      time was determined by tracking results within individual terms and cumulatively,
      across terms. Applying this replication strategy, DE's overall impact was modest
      (an effect size of approximately .20) but quite consistent, based on parametric
      and nonparametric estimation approaches. A meta-analysis of five RD results
      yielded virtually the same estimate as the overall, parametric findings. Subset
      analysis, though tentative, suggested that males benefited more than females,
      while academic gains were comparable for different ethnicities. CONCLUSION: The
      cumulative, within-study comparison, replication approach offers considerable
      potential for the evaluation of new and existing policies, particularly when
      effects are relatively small, as is often the case in applied settings.

PMID- 24662604
TI  - Distal volar radial plates: how anatomical are they?
AB  - BACKGROUND: Fractures of the distal radius are common, with volar locking plates
      being increasingly used in their treatment. They aim to provide stable internal
      fixation and are designed to mirror the natural anatomy. Current volar plate
      designs incorporate a volar cortical angle (VCA) of 25 degrees. HYPOTHESIS: The
      aim of this study is to determine whether the VCA in uninjured distal radii
      corresponds accurately with modern volar plate designs. MATERIALS AND METHODS: A
      retrospective radiological analysis utilizing Computed Tomography scans to assess
      the VCA of 100 distal radii. Each distal radius was subjected to 3 measurements
      of the VCA in the sagittal plane. RESULTS: One hundred patients were identified
      (67 male, 33 female; mean age 37.4 years). The mean VCA was 32.9 degrees (S.D.+/
      5.14 degrees). The VCA in male patients was significantly greater than in females
      (33.6 vs 31.5 degrees; P=0.04). There was a statistically significant difference
      between the lateral VCA and medial VCA (32.2 vs 34.3 degrees, P=0.02).
      DISCUSSION: Our study clearly demonstrates that the VCA measured in the distal
      radius is significantly greater than the volar angulation incorporated within
      modern plate design. Given that the aim of ORIF is to anatomically reconstruct
      the distal radius, our study highlights that this may not be possible with
      current plates. LEVELS OF EVIDENCE: Level IV Retrospective case series.

PMID- 24662605
TI  - GM-CSF induces cyclin D1 expression and proliferation of endothelial progenitor
      cells via PI3K and MAPK signaling.
AB  - BACKGROUND/AIMS: Endothelial progenitor cells (EPCs), which can be isolated from
      the bone marrow or the peripheral blood, have generated interest because of their
      capacity to migrate to sites of vascularization and endothelialization and
      differentiate into endothelial cells in a process termed neovasculogenesis. EPCs
      are therefore possible regenerative tools for the treatment of vascular diseases
      and potential targets for the inhibition of angiogenesis during tumor
      development. Here, we investigated the mechanisms underlying the effect of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) on the acceleration of
      EPC proliferation and colony formation. METHODS: EPCs were isolated, identified
      and cultured in the presence of GM-CSF. The effect of GM-CSF on endothelial cell
      colony formation and proliferation was examine by colony formation assay and MTT
      assay, separately. Cell cycle was analyzed by flow cytometry. The expression of
      cyclin D1 and cyclin E were detected by western bloting. JAK/Stat, PI3K/Akt and
      MAPK signaling were analyzed. RESULTS: GM-CSF accelerated the G1/S phase
      transition in EPCs by upregulating the expression of cyclins D1 and E. The GM-CSF
      induced increase in the levels of cyclin D1 and the subsequent phosphorylation of
      the retinoblastoma (Rb) protein activated E2F-1, resulting in the upregulation of
      the transcription of cyclin E. Furthermore, the induction of cyclin D1 expression
      and cell cycle progression by GM-CSF was mediated by the PI3K/Akt, JNK and ERK
      signaling pathways through the phosphorylation of GSK3beta or the activation of
      AP-1 transcription factors. CONCLUSION: Our findings shed light on the mechanisms
      underlying the effect of GM-CSF on the modulation of cell cycle progression in
      EPCs, which is important considering their role in vascular repair and their
      therapeutic potential in several diseases.

PMID- 24662606
TI  - Role of virus-encoded microRNAs in Avian viral diseases.
AB  - With total dependence on the host cell, several viruses have adopted strategies
      to modulate the host cellular environment, including the modulation of microRNA
      (miRNA) pathway through virus-encoded miRNAs. Several avian viruses, mostly
      herpesviruses, have been shown to encode a number of novel miRNAs. These include
      the highly oncogenic Marek's disease virus-1 (26 miRNAs), avirulent Marek's
      disease virus-2 (36 miRNAs), herpesvirus of turkeys (28 miRNAs), infectious
      laryngotracheitis virus (10 miRNAs), duck enteritis virus (33 miRNAs) and avian
      leukosis virus (2 miRNAs). Despite the closer antigenic and phylogenetic
      relationship among some of the herpesviruses, miRNAs encoded by different viruses
      showed no sequence conservation, although locations of some of the miRNAs were
      conserved within the repeat regions of the genomes. However, some of the virus
      encoded miRNAs showed significant sequence homology with host miRNAs
      demonstrating their ability to serve as functional orthologs. For example, mdv1
      miR-M4-5p, a functional ortholog of gga-miR-155, is critical for the oncogenicity
      of Marek's disease virus. Additionally, we also describe the potential
      association of the recently described avian leukosis virus subgroup J encoded E
      (XSR) miRNA in the induction of myeloid tumors in certain genetically-distinct
      chicken lines. In this review, we describe the advances in our understanding on
      the role of virus-encoded miRNAs in avian diseases. 

PMID- 24662608
TI  - Interhospital variation in reperfusion rates following endovascular treatment for
      acute ischemic stroke.
AB  - BACKGROUND: Patients who have successful reperfusion following endovascular
      therapy for acute ischemic stroke have improved clinical outcomes. We sought to
      determine if the chance of successful reperfusion differs among hospitals, and if
      hospital site is an independent predictor of reperfusion. METHODS: Nine hospitals
      recruited patients in the Diffusion and Perfusion Imaging Evaluation for
      Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of
      endovascular stroke treatment conducted between 2008 and 2011. Patients were
      included for analysis if they had a baseline Thrombolysis in Cerebral Infarction
      (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion
      score of 2b or 3 at completion of the procedure. Collaterals were assessed using
      the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3
      4). The association between hospital site and successful reperfusion was first
      assessed in an unadjusted analysis and subsequently in a multivariate analysis
      that adjusted for predictors of successful reperfusion. RESULTS: 36 of 89
      patients (40%) achieved successful reperfusion. The rate of reperfusion varied
      from 0% to 77% among hospitals in the univariate analysis (chi(2) p<0.001) but
      hospital site did not remain as an independent predictor of reperfusion in
      multivariate analysis (p=0.81) after adjustment for the presence of good
      collaterals (p<0.01) and use of the Merci retriever (p<0.05). CONCLUSIONS:
      Reperfusion rates vary among hospitals, which may be related to differences in
      treatment protocols and patient characteristics. Additional studies are needed to
      identify all of the factors that underlie this variability as this could lead to
      strategies that reduce interhospital variability in reperfusion rates and improve
      clinical outcomes.

PMID- 24662607
TI  - Gene therapy targeting HIV entry.
AB  - Despite the unquestionable success of antiretroviral therapy (ART) in the
      treatment of HIV infection, the cost, need for daily adherence, and HIV
      associated morbidities that persist despite ART all underscore the need to
      develop a cure for HIV. The cure achieved following an allogeneic hematopoietic
      stem cell transplant (HSCT) using HIV-resistant cells, and more recently, the
      report of short-term but sustained, ART-free control of HIV replication following
      allogeneic HSCT, using HIV susceptible cells, have served to both reignite
      interest in HIV cure research, and suggest potential mechanisms for a cure. In
      this review, we highlight some of the obstacles facing HIV cure research today,
      and explore the roles of gene therapy targeting HIV entry, and allogeneic stem
      cell transplantation in the development of strategies to cure HIV infection. 

PMID- 24662609
TI  - Adhesive glove CPR: does it really fit alone?

PMID- 24662610
TI  - Reply to Letter: A pilot study examining the role of regional cerebral oxygen
      saturation monitoring as a marker of return of spontaneous circulation in
      shockable (VF/VT) and non-shockable (PEA/Asystole) cause of cardiac arrest.

PMID- 24662611
TI  - Reply to letter: Adhesive glove CPR: does it really fit alone?

PMID- 24662612
TI  - Reply to letter: "Regional cerebral oxygen saturation monitoring during cardiac
      arrest".

PMID- 24662613
TI  - Reply letter to: A pilot study examining the role of regional cerebral oxygen
      saturation monitoring as a marker of return of spontaneous circulation in
      shockable (VF/VT) and non-shockable (PEA/Asystole) causes of cardiac arrest.

PMID- 24662614
TI  - Regional cerebral oxygen saturation monitoring during cardiac arrest.

PMID- 24662615
TI  - Right upper-quadrant pain in a patient with drug abuse, secondary syphilis and
      occult hepatitis B virus.
AB  - OBJECTIVE: To describe the etiology of hepatitis and identify occult hepatitis B
      virus (HBV) infection. CLINICAL PRESENTATION AND INTERVENTION: A 40-year-old man
      presented with severe abdominal pain and jaundice, a history of acute HBV
      infection that had cleared as well as the use of acetaminophen, methamphetamine,
      buprenorphine and marijuana. He admitted to having had unprotected sex with
      multiple partners of both genders. A thorough skin examination revealed
      papulosquamous lesions on his penis, scrotum, upper and lower extremities and
      feet. Transaminases and bilirubin were elevated. His rapid plasma reagin was
      reactive, and hepatitis serologies showed occult HBV. Liver biopsy showed severe
      hepatitis, but the stains for hepatitis B surface antigen and hepatitis B core
      antigen were negative. The pathological findings were highly indicative of drug
      induced hepatitis without evidence of chronic hepatitis, reactivation of HBV or
      syphilitic hepatitis. With supportive management and abstinence from drugs, his
      condition improved. CONCLUSION: This case describes a patient with multiple
      potential causes for hepatitis and highlights the importance of obtaining a
      detailed social history. Further, one should consider the presence of occult HBV
      and recognize the serologic pattern.

PMID- 24662616
TI  - Functional communication of children who are deaf or hard-of-hearing.
AB  - OBJECTIVE: The primary aim of this study was to investigate the relationship
      between language levels and communication and social function skills in young
      children who are deaf/hard-of-hearing. METHOD: A cross-sectional design was used
      with participants sampled predominately from a single clinic setting. Children
      between 3 and 6 years of age with permanent bilateral hearing loss were enrolled
      in the study. All children received the Preschool Language Scales-Fifth Edition
      language assessment and a neurocognitive assessment using the Leiter
      International Performance Scale-Revised at the study visit. Communication and
      social function skills were measured using the Vineland Adaptive Behavior Scales
      Second Edition (VABS-II; mean 100 +/- 15) and the Pediatric Evaluation of
      Disability Inventory (PEDI; mean 50 +/- 10). RESULTS: Analysis included 65
      children with mild to profound bilateral hearing loss (mean age 56.8 months, SD
      +/- 14.1); 52% had hearing loss in the mild to moderate range. The mean nonverbal
      intelligence quotient (IQ) was 95.7 (+/-18.8), the mean receptive language
      standard score was 83.7 (+/-18.6), and mean expressive language standard score
      was 83.0 (+/-18.5). The mean VABS-II communication standard score was 89.1 (+/
      17.5), and the mean PEDI social function score was 39.6 (+/-15.3). Both nonverbal
      IQ and receptive language relative to nonverbal IQ (the ratio of language to IQ)
      were significantly associated with communication and social functioning,
      explaining more than 50% of the variance in communication function scores.
      Children with language commensurate with their IQ had significantly higher
      communication and social function scores than children with language
      significantly lower than IQ. This finding was consistent across different levels
      of IQ and independent of degree of hearing loss. CONCLUSION: Even with early
      identification and intervention, hearing loss continues to have a life-long
      impact on functioning. It is important to identify when language levels are not
      meeting a child's capabilities in order to intervene most effectively.

PMID- 24662617
TI  - Parent and provider perspectives on procedural care for children with autism
      spectrum disorders.
AB  - OBJECTIVE: Children with autism spectrum disorders (CWASDs) have more difficulty
      tolerating hospital procedures than many other children. The aim of this study
      was to identify parent and provider perspectives on barriers and facilitators to
      procedural care for CWASDs. METHODS: Semistructured interviews were conducted
      with medical staff and parents of CWASDs. Those parents whose child with autism
      required a procedure in a tertiary care sedation unit and those whose child was
      enrolled in autismMatch (a research registry for individuals with autism) were
      recruited. Staff providing direct patient care in the tertiary care sedation unit
      were recruited. Participants were asked open-ended questions about factors
      contributing to or interfering with successful completion of medical procedures
      for CWASDs. Interviews were audio-recorded, transcribed verbatim, coded, and
      analyzed using modified grounded theory techniques. RESULTS: Twenty mothers and
      20 medical staff members were interviewed. Participants described 2 domains
      essential to care of CWASDs but in which barriers existed: (1) productive
      interactions between providers and families, largely dependent on advanced
      preparation and (2) modifications to healthcare organization and delivery in the
      areas of patient flow and clinical environment. Individualized care is essential
      to quality care in both domains. CONCLUSIONS: Children with autism spectrum
      disorders require individualized interventions to maximize the quality of
      procedural care. However, many hospitals and providers are not sufficiently
      equipped to accommodate these children's needs. This study suggests that targeted
      improvements in preparation and communication between providers and families as
      well as modifications in patient flow and clinical environments have the
      potential to improve the quality and successful completion of procedures.

PMID- 24662618
TI  - Strontium does not affect the intrinsic bone quality at tissue and BSU levels in
      iliac samples from Macaca fascicularis monkeys.
AB  - Our purpose was to evaluate the impact of strontium ranelate (SrRan) on bone
      mineral quality at both tissue and bone structural unit (BSU) levels. Thirty
      iliac bone samples (dehydrated then embedded) were taken from monkeys who
      received 0 (controls), 200, 500 or 1250 mg/kg/day of SrRan for 52 weeks and were
      sacrificed either at the end of administration (treated animals, n=16) or 10
      weeks later (reverse animals, n=14). Degree of mineralization (DMB),
      heterogeneity index of mineralization (HI), Vickers microhardness (Hv) and focal
      bone strontium content (BSC) were measured globally at tissue level and focally
      on the same 923 BSUs. Mineral and collagen characteristics, as well as
      chemometric analyses were performed on younger and older tissues in cortical bone
      and cancellous bone in 737 other BSUs. At tissue level, SrRan preserved material
      properties. At BSU level, BSC increased (significant) dose dependently in treated
      and reverse animals. DMB and Hv were greater in older than in younger bone in
      controls and treated animals. In treated animals, DMB was positively correlated
      with Hv and inversely correlated with the BSC. Thus, younger BSUs were less
      mineralized and less hard than older BSUs independently from the presence of
      strontium. Mineral maturity, crystallinity index, mineralization index,
      carbonation and collagen maturity were not modified by SrRan. Chemometry
      confirmed the absence of a direct effect of strontium on mineralization. Thus,
      surrogates of micro- and nano-structural mineral properties were not altered by
      SrRan and remained at a physiological level.

PMID- 24662619
TI  - Undercarboxylated osteocalcin, muscle strength and indices of bone health in
      older women.
AB  - We investigated the association between undercarboxylated osteocalcin (ucOC) and
      lower-limb muscle strength in women over the age of 70years. The study also aims
      to confirm the association between bone turnover markers and heel ultrasound
      measures. A post-hoc analysis using data collected as part of a randomized
      placebo-controlled trial of vitamin D supplementation. An immunoassay was used to
      quantify total OC (tOC), with hydroxyapatite pre-treatment for ucOC. We
      determined associations of absolute and relative (ucOC/tOC; ucOC%) measures of
      ucOC with lower-limb muscle strength, heel ultrasound measures of speed of sound
      (SOS) and broadband ultrasound attenuation (BUA), bone turnover markers (BTMs;
      P1NP and CTx) and the acute phase protein alpha-1-antichymotrypsin (alpha-ACT).
      ucOC%, but not absolute ucOC concentration, was positively associated with hip
      flexor, hip abductor and quadriceps muscle strength (all p<0.05). ucOC% was
      negatively associated with alpha-ACT (beta-coefficient=-0.24, p=0.02). tOC was
      positively associated with both P1NP and CTx (p<0.001). For each per unit
      increase in tOC (MUg/L) there was a corresponding lower BUA, SOS and SI (beta
      coefficient = -0.28; -0.23 and -0.23, respectively; all p<0.04). In conclusion,
      ucOC% is positively associated with muscle strength and negatively associated
      with alpha-ACT. These data support a role for ucOC in musculoskeletal
      interactions in humans. Whilst tOC is associated with bone health, ucOC% and ucOC
      may also be linked to falls and fracture risk by influencing muscle function.

PMID- 24662620
TI  - Thyroid and the heart.
AB  - Thyroid hormones modulate every component of the cardiovascular system necessary
      for normal cardiovascular development and function. When cardiovascular disease
      is present, thyroid function tests are characteristically indicated to determine
      if overt thyroid disorders or even subclinical dysfunction exists. As
      hypothyroidism, hypertension, and cardiovascular disease all increase with
      advancing age, monitoring of thyroid-stimulating hormone, the most sensitive test
      for hypothyroidism, is important in this expanding segment of our population. A
      better understanding of the impact of thyroid hormonal status on cardiovascular
      physiology will enable health care providers to make decisions about thyroid
      hormone evaluation and therapy in concert with evaluating and treating
      hypertension and cardiovascular disease. The goal of this review is to access
      contemporary understanding of the effects of thyroid hormones on normal
      cardiovascular function and the potential role of overt and subclinical
      hypothyroidism and hyperthyroidism in a variety of cardiovascular diseases.

PMID- 24662622
TI  - A case study of Mycobacterium avium complex infection presenting with acute
      pericarditis.

PMID- 24662621
TI  - Errata in medical publications.
AB  - BACKGROUND: Information is limited about the communication of corrections or
      errors in the medical literature; therefore, we sought to determine the frequency
      and significance of published errata in high impact factor journals. METHODS:
      Retrospective evaluation of errata reports for articles published in 20 English
      language general medicine and cardiovascular journals (mean impact factor, 12.23;
      median, 5.52) over 18 months. Each independently adjudicated erratum was
      categorized by location in the article and qualitative categories of severity.
      Descriptive statistics and Spearman's rank correlation coefficients were computed
      to describe the association between author and errata number. Source of error,
      association between impact factor and errata occurrence, and errata rate by
      journal were assessed. RESULTS: A total of 557 articles were associated with
      errata reports (overall errata report occurrence 4.2 per 100 published original
      and review articles; mean of 2.4 errors per errata report). At least 1 major
      error that materially altered data interpretation was present in 24.2% of
      articles with errata. There was a strong association between impact factor and
      errata occurrence rate (rho = 0.869, P < .001). Across all errata, 51.0% were not
      corrected or the report did not specify whether a correction was made.
      CONCLUSIONS: The reporting of errata across journals lacks uniformity. Despite
      published criteria for authorship that mandate final approval of the manuscript
      by all authors, errors are frequent, including those that may materially change
      the interpretation of data. Increased vigilance by authors to prevent errata and
      consensus by journal editors on the format of reporting are warranted.

PMID- 24662623
TI  - Estimating iron overload in patients with suspected liver disease and elevated
      serum ferritin.
AB  - BACKGROUND: Iron status evaluation in patients with suspected liver disease and
      elevated serum ferritin is often challenging because hyperferritinemia does not
      always indicate iron overload. A reliable approach to estimate iron overload
      without exposing the patient to unnecessary investigations would help the
      clinician to identify patients who may take advantage of iron-removal therapy.
      METHODS: We analyzed all liver biopsies, including measurement of hepatic iron
      concentration, performed at the University Hospital Zurich from 1997 to 2010 to
      identify clinical and laboratory predictors of iron overload in patients with
      elevated serum ferritin (n = 147). RESULTS: Hyperferritinemia was predictive of
      iron overload only in patients with a high level of serum ferritin (>2000 MUg/L).
      In patients with moderate hyperferritinemia, liver transaminases inversely
      correlated with hepatic iron concentration. A combination of both parameters
      expressed as ferritin/aspartate transaminase ratio was highly predictive of
      tissue iron overload (sensitivity 83.3%, specificity 78.6%). Receiver operating
      characteristic analysis resulted in an area under the curve of 0.83. CONCLUSIONS:
      We established a simple and reliable method to correctly estimate iron overload
      in patients with suspected liver disease and elevated serum ferritin.

PMID- 24662624
TI  - Culture-negative prosthetic joint arthritis related to Coxiella burnetii.
AB  - BACKGROUND: The number of hip and knee arthroplasty procedures is steadily
      increasing as life expectancy increases. Coxiella burnetii may be responsible for
      culture-negative prosthetic joint arthritis and is associated with antibiotic
      failure and repeated surgeries. We report the first case series of C. burnetii
      related culture-negative prosthetic joint arthritis. METHODS: Cases were
      retrieved from the French National Referral center for Q fever. Diagnosis was
      based on (18)fluorodeoxyglucose positron emission tomography, serology, broad
      range polymerase chain reaction, and C. burnetii-specific polymerase chain
      reaction. RESULTS: Four cases of C. burnetii-related culture-negative prosthetic
      joint arthritis were found. Standard bacteriologic procedures would have missed
      the diagnosis in all cases. Etiologic diagnosis improved the outcome in all but 1
      case. CONCLUSIONS: A systematic, comprehensive diagnostic strategy should be used
      in culture-negative prosthetic joint arthritis, including testing for C. burnetii
      in endemic areas.

PMID- 24662625
TI  - Web-based intervention in mindfulness meditation for reducing residual depressive
      symptoms and relapse prophylaxis: a qualitative study.
AB  - BACKGROUND: Mindful Mood Balance (MMB) is a Web-based intervention designed to
      treat residual depressive symptoms and prevent relapse. MMB was designed to
      deliver the core concepts of mindfulness-based cognitive therapy (MBCT), a group
      treatment, which, despite its strong evidence base, faces a number of
      dissemination challenges. OBJECTIVE: The present study is a qualitative
      investigation of participants' experiences with MMB. METHODS: Qualitative content
      analysis was conducted via 38 exit interviews with MMB participants. Study
      inclusion required a current PHQ-9 (Patient Health Questionnaire) score <=12 and
      lifetime history >=1 major depressive episode. Feedback was obtained on specific
      website components, program content, and administration as well as skills
      learned. RESULTS: Codes were assigned to interview responses and organized into
      four main themes: MBCT Web content, MBCT Web-based group process, home practice,
      and evidence of concept comprehension. Within these four areas, participants
      highlighted the advantages and obstacles of translating and delivering MBCT in a
      Web-based format. Adding increased support was suggested for troubleshooting
      session content as well as managing time challenges for completing home
      mindfulness practice. Participants endorsed developing affect regulation skills
      and identified several advantages to Web-based delivery including flexibility,
      reduced cost, and time commitment. CONCLUSIONS: These findings support the
      viability of providing MBCT online and are consistent with prior qualitative
      accounts derived from in-person MBCT groups. While there is certainly room for
      innovation in the domains of program support and engagement, the high levels of
      participant satisfaction indicated that MMB can significantly increase access to
      evidence-based psychological treatments for sub-threshold symptoms of unipolar
      affective disorder.

PMID- 24662626
TI  - Performance outcomes for borderline cochlear implant recipients with substantial
      preoperative residual hearing.
AB  - OBJECTIVE: This study examined whether cochlear implant (CI) recipients with
      substantial preoperative residual hearing obtained more benefit from a CI than
      from a hearing aid (HA). STUDY DESIGN: Retrospective records review. SETTING:
      Tertiary referral center. PATIENTS: Thirty-seven CI recipients (11
      children/teens, 26 adults) were identified that met the following inclusion
      criteria: preimplant sentence recognition scores greater than 50% correct in the
      implanted ear or greater than 60% in the best-aided/binaural condition (Group 1,
      n = 18); audiometric thresholds less than 70 dB HL at 2 or more frequencies
      (i.e., better than a severe-profound hearing loss; Group 2, n = 13 ears in 12
      recipients), or those that met both the audiometric and sentence-recognition
      criteria (Group 3, n = 7). MAIN OUTCOME MEASURE: Postimplant speech-perception
      scores. RESULTS: Postimplant speech perception was substantially better than the
      preimplant performance for 12 of 18 recipients in Group 1, 10 of 12 recipients
      (11/13 ears) in Group 2, and 5 of 7 recipients in Group 3 (total, 73.7%). Five
      recipients (13.1%) showed no change from preimplant performance levels. Results
      were inconclusive for 2 recipients (5.3%) because preimplant versus postimplant
      testing was conducted in different conditions. Three recipients (7.9%) exhibited
      decreased performance postimplant. CONCLUSION: For most recipients whose hearing
      was better than that defined by traditional candidacy criteria, performance
      improved with the CI. These results may help clinicians guide candidates in the
      decision-making process by providing information on the range of outcomes for
      recipients with similar preimplant performance levels, identify the need for
      additional preimplant counseling regarding expectations, and recognize the
      importance of systematizing preimplant and postimplant testing for longitudinal
      assessment of performance.

PMID- 24662627
TI  - Management of endolymphatic sac tumors: sporadic cases and von Hippel-Lindau
      disease.
AB  - OBJECTIVE: To analyze the difference between the endolymphatic sac tumors (ELSTs)
      in sporadic cases and in von Hippel-Lindau (VHL) disease. STUDY DESIGN:
      Retrospective case review in a tertiary referral center. PATIENTS AND METHODS:
      Fourteen cases of ELST, occurring since 1998, were reviewed. We analyzed the
      initial symptoms, characteristics of the tumor, treatment, sequelae, and follow
      up for each group. RESULTS: The ELSTs were sporadic in 6 cases and associated
      with VHL disease in 8 cases. The mean age at the time of the first surgery was 26
      years (range, 12-41). All except two of the patients presented with a unilateral
      tumor. The initial symptoms were hearing loss (n = 9), tinnitus (n = 7), and/or
      vertigo (n = 5). Hearing loss was more prevalent in the sporadic cases.
      Preoperative arteriography was performed for 4 patients, with embolization
      performed for 1 patient. The size of the tumor was significantly larger in the
      sporadic cases (31.7 mm) than in the cases of VHL disease (19.3 mm). The surgical
      approach was more extensive in the sporadic cases. The surgeons found 2 types of
      tumors. Cystic tumors with massive bleeding invading the surrounding structures
      (the dura mater or jugular bulb) were more common in the sporadic cases. Fibrous
      tumors that infiltrate the bone and have moderate bleeding were more common in
      the cases associated with VHL disease.Two patients with small lesions were not
      operated on but were followed for 6 years without tumor growth. They died of
      metastasis from gastric and kidney cancer. Four recurrences occurred during the
      14 years of follow-up. Four facial palsies and 8 cases of profound deafness were
      encountered postoperatively. CONCLUSION: Sporadic tumors are more aggressive than
      those associated with VHL disease. Complete surgical resection should be the goal
      of treatment. Preoperative angiography with embolization is recommended. In some
      cases, embolization may be impossible, and preoperative or postoperative
      radiotherapy should be discussed.

PMID- 24662629
TI  - Otoprotective properties of mannitol against gentamicin induced hair cell loss.
AB  - BACKGROUND: Gentamicin is a widely used antibiotic, which causes hearing loss
      because of destruction of auditory hair cells. Mannitol has been shown to have
      cytoprotective properties in the cochlea both in vitro and in vivo. Mannitol has
      been shown to be safe in concentrations up to 100 mM in organ of Corti explants.
      It is proposed as an otoprotective agent against gentamicin ototoxicity. METHODS:
      Organ of Corti were dissected from P-3 rat pups and cultured under the following
      conditions for 96 hours: 1) control, 2) gentamicin (10 MUM for all hair cell
      count experiments), 3) gentamicin + mannitol 10 mM, 4) gentamicin + mannitol 50
      mM, and 5) gentamicin + mannitol 100 mM. The tissues were then fixed and stained,
      and hair cells were counted for segments of the apex, middle, and basal turns.
      Quantitative RT-PCR (qRT-PCR) was performed on organ of Corti explant extracted
      RNA after 24 hours in vitro: 1) control; 2) gentamicin (100 MUM for all gene
      expression and CellRox experiments); 3) gentamicin +mannitol 100 mM; and 4)
      mannitol 100 mM for tumor necrosis factor-alpha (TNF-alpha), TNF-alpha receptor
      (TNFR1A), interleukin-1 beta (IL-1beta) and cyclooxygenase-2 (COX-2). In vitro
      examination of oxidative stress was performed for the same test groups at 24
      hours using CellRox Deep Red assay. RESULTS: Gentamicin induced loss of both
      inner hair cells and outer hair cells with increasing severity from apex to
      middle to basal segments (Pearson r = -0.999 for inner hair cells and -0.972 for
      outer hair cells). Mannitol demonstrated dose-dependent otoprotection of IHCs and
      outer hair cells (p < 0.001 for mannitol at 100 mM). CellRox demonstrated
      increased oxidative stress induced by gentamicin exposure, and this effect was
      attenuated by treatment of gentamicin-exposed explants with mannitol (p < 0.05).
      TNF-alpha, IL-1beta TNFR1A, and COX-2 mRNA levels were upregulated by gentamicin
      (p < 0.05). Mannitol treatment of gentamicin explants downregulated the gene
      expression of the proinflammatory cytokines, but this difference did not achieve
      significance. Interestingly, in gentamicin-challenged organ of Corti explants,
      Mannitol upregulated the expression of TNFR1A, but this increase did not achieve
      significance (p > 0.05). CONCLUSION: Gentamicin ototoxicity is increasingly
      severe from the apex to basal turn of the cochlea. Treatment with mannitol
      prevents gentamicin-induced hair cell loss in a dose-dependent manner, protecting
      both IHCs and outer hair cells. Mannitol appears to act as a free radical
      scavenger to reduce the cytotoxic effects of gentamicin by reducing the level of
      oxidative stress.

PMID- 24662628
TI  - Relationship of hearing loss and dementia: a prospective, population-based study.
AB  - OBJECTIVE: To determine whether baseline hearing loss increases cognitive decline
      and risk for all-cause dementia in a population of elderly individuals. STUDY
      DESIGN: Longitudinal cohort study. SETTING: Community-based, outpatient.
      PATIENTS: Men and women aged 65 years or older without dementia at baseline.
      INTERVENTION(S): All subjects completed the Modified Mini-Mental Status Exam (3MS
      R) at baseline and over 3 triennial follow-up visits. Hearing loss (HL) at
      baseline was based on observation of hearing difficulties during testing or
      interview. Incident dementia was determined by clinical assessment and expert
      consensus. MAIN OUTCOME MEASURE(S): Dementia and 3MS-R score. RESULTS: At
      baseline, 4,463 subjects were without dementia, 836 of whom had HL. Of those with
      HL, 16.3% developed dementia, compared with 12.1% of those without HL (p <
      0.001). Mean time to dementia was 10.3 years in the HL group versus 11.9 years
      for non-HL (log rank test p < 0.001). In Cox regression analyses controlling for
      sex, presence of APOE- [Latin Small Letter Open E]4 allele, education, and
      baseline age, and cardiovascular risk factors, HL was an independent predictor of
      developing dementia (hazard ratio = 1.27, p = 0.026 [95% CI, 1.03-1.56]). Linear
      mixed models controlling for similar covariates showed HL was associated with
      faster decline on the 3MS-R, at a rate of 0.26 points/year worse than those
      without HL. CONCLUSION: Elderly individuals with HL have an increased rate of
      developing dementia and more rapid decline on 3MS-R scores than their nonhearing
      impaired counterparts. These findings suggest that hearing impairment may be a
      marker for cognitive dysfunction in adults age 65 years and older.

PMID- 24662630
TI  - Focal sclerosis of semicircular canals with severe DFNA9 hearing impairment
      caused by a P51S COCH-mutation: is there a link?
AB  - HYPOTHESIS: Focal sclerosis of one or more semicircular canals on computed
      tomographic (CT) scans and a corresponding signal loss on magnetic resonance (MR)
      imaging are radiologic lesions that are linked to patients who are suffering from
      advanced otovestibular impairment caused by hereditary DFNA9 hearing loss.
      BACKGROUND: DFNA9 is a hereditary hearing loss that is characterized by late
      onset progressive imbalance and hearing deterioration, caused by mutations in the
      COCH gene. To date, no radiologic lesions have been associated with this
      condition. STUDY DESIGN: A retrospective chart review SETTING: Tertiary referral
      center SUBJECTS: The radiologic data of 9 patients who presented between 2007 and
      2012 with otovestibular deterioration caused by a mutation in the COCH gene were
      reviewed. RESULTS: All 9 subjects were carriers of the same c.151C > T,
      p.Pro51Ser (P51S) - missense mutation in the COCH gene. In 8 of them similar
      sclerotic lesions and/or narrowing were demonstrated in one or more semicircular
      canals on computed tomography CT scan, with a signal loss at corresponding areas
      on T2-weighted magnetic resonance (MR) images. In 1 patient, the posterior part
      of the vestibule was also affected. The posterior canals were affected in most
      cases (58%), compared with the superior (21%) and lateral canals (16%) or the
      vestibule (5%). Only 68.4% of the lesions on MR images were also visible on CT
      scans, suggesting a fibrotic process without calcification. Ears presenting
      radiologic lesions showed significantly more severe hearing loss (median PTA 104
      dB HL) compared with unaffected ears (58 dB HL). CONCLUSION: Eight of 9 subjects
      with the same P51S mutation in the COCH gene showed similar radiologic lesions,
      affecting the PSCC in the majority of the cases. These radiologic abnormalities
      occurred in more advanced stages of the otovestibular deterioration, supporting
      the hypothesis that these lesions might represent the end phase of a low-grade
      chronic inflammation or protein deposition. A new phenotypic and characteristic
      radiologic feature of DFNA9 has been discovered.

PMID- 24662631
TI  - Congenital middle ear abnormalities with absence of the oval window: diagnosis,
      surgery, and audiometric outcomes.
AB  - OBJECTIVE: Congenital absence of the oval window (CAOW) is a rare condition in
      which the stapes footplate fails to develop, resulting in a significant
      conductive hearing loss in the affected ear. The purpose of this study was to
      describe the surgical management and outcomes of patients with CAOW undergoing
      the oval window drill-out (OWD) procedure. MATERIALS AND METHODS: A retrospective
      chart review of patients with CAOW between 1996 and 2011 was performed. Clinical
      data of patients who underwent OWD were collected. Seventy-nine patients (103
      ears) were confirmed using exploratory tympanotomy as having congenital stapes
      anomalies and CAOW without any anomalies of the tympanic membrane and external
      auditory canal. Demographic data, CT findings, operative findings, complications,
      and preoperative/postoperative audiometry data of patients who underwent OWD were
      collected. The preoperative and postoperative audiologic findings were analyzed
      in 42 patients (56 ears) with complete data. RESULTS: Hearing restoration surgery
      was aborted for various reasons in 14 cases. Six patients underwent revision
      operations for worsening hearing after their first surgery. The average
      preoperative 4 tone air conduction threshold was 67 dB; the average 6-month
      postoperative four tone air conduction threshold was 49 dB, and the average
      postoperative hearing gain was 18 dB. For the 56 ears, the average 4 tone air
      conduction threshold 6 months after surgery was significantly lower than the
      preoperative threshold. CONCLUSION: The oval window drill-out procedure is a
      viable operation for patients with congenital absence of the oval window, and it
      is important for surgeons to develop personalized treatment programs to improve
      patients' hearing with minimal complications.

PMID- 24662632
TI  - An experimental objective method to determine maximum output and dynamic range of
      an active bone conduction implant: the Bonebridge.
AB  - INTRODUCTION: Recently, a new active bone conduction implant, the Bonebridge, was
      introduced. This transcutaneous device is proposed as an alternative to previous
      percutaneous systems. The current study aims to determine the maximum output (MO)
      of the Bonebridge by making use of Bonebridge-generated sound pressure levels in
      the occluded ear canal of the unaided ear. METHODOLOGY: The test setup consisted
      of audiometry and input-output measurements. These tests were performed on 3
      Bonebridge users with conductive or mixed hearing loss (bone-conduction
      thresholds, <= 45 dB HL) at least 3 months after implantation surgery. All the
      patients were implanted and were evaluated in the Antwerp University Hospital.
      The MO of the device was determined by measuring input-output functions with a
      microphone placed in the occluded contralateral ear canal using the Aurical REM
      system. During testing, the sound processor was fitted in linear amplification
      mode and with unlimited output to determine the MO and the input dynamic range of
      the Bonebridge. This experimental setup intends to evaluate the device in a
      fitting program without compression. RESULTS: The mean MO of the device was 55 dB
      HL (SD, 6 dB HL) at 0.5 kHz, 61 dB HL (SD, 18 dB HL), 71 dB HL (SD, 10 dB HL) at
      2 kHz, and 60 dB HL (SD, 10 dB HL) at 4 kHz. The mean dynamic range of the
      Bonebridge was 41 (SD, 5) dB HL, 46 (SD, 10) dB HL, 46 (SD, 5) dB HL, and 37 (SD,
      16) dB HL for 0.5, 1, 2, and 4 kHz, respectively. CONCLUSION: In summary, ear
      canal measures can effectively be used to assess input-output behavior of the
      Bonebridge. The present study indicates that the MO of the Bonebridge ranges from
      55 to 71 dB HL, depending on frequency. Accepting a minimum dynamic range of 35
      dB with the Bonebridge, fitting of the Bonebridge in a linear program is
      advocated in patients with a sensorineural hearing loss component of up to 30 dB
      HL.

PMID- 24662634
TI  - Imaging case of the month. Multifocal epithelioid hemangioendothelioma with
      massive lateral skull base involvement.

PMID- 24662633
TI  - Sensorineural hearing loss in people with deletions of 18q: hearing in 18q-.
AB  - OBJECTIVE: The objective of this study was to characterize hearing loss in
      individuals with deletions of distal chromsome18q and to identify the smallest
      region of overlap of their deletions, thereby identifying potential causative
      genes. STUDY DESIGN: The clinical data were collected via a retrospective case
      study. Molecular data were obtained via high-resolution chromosome microarray
      analysis. SETTING: The study was conducted as a component of the ongoing research
      protocols at the Chromosome 18 Clinical Research Center at the University of
      Texas Health Science Center at San Antonio. PATIENTS: Thirty-eight participants
      with a deletion of the distal portion of the long arm of chromosome 18 were
      recruited to this study. INTERVENTIONS: The participants underwent an otologic
      examination as well as a basic audiometry evaluation. Blood samples were
      obtained, and high-resolution chromosome microarray analysis was performed. MAIN
      OUTCOMES MEASURES: Pure tone averages and speech discrimination scores were
      determined for each participant. The region of hemizygosity for each participant
      was determined to within 2 Kb each of their breakpoints. RESULTS: Twenty-four
      participants (63%) had high-frequency hearing loss, similar to the pattern seen
      in presbycusis. Comparison of microarray results allowed identification of eight
      genes, including the candidate gene for dysmyelination (MBP). CONCLUSION:
      Individuals with a deletion of a 2.8 Mb region of 18q23 have a high probability
      (83%) of high-frequency sensorineural hearing loss.

PMID- 24662635
TI  - Pars tensa retractions without cholesteatoma in children: predictors for
      ossicular chain destruction, air conduction thresholds, and postoperative
      retractions.
AB  - OBJECTIVE: Determine predictive values of preoperative stages of pars tensa
      retractions, coexisting attic retraction and preoperative air conduction for
      ossicular destruction in isolated and combined pars tensa retraction, and
      predictors for successful tympanic grafts after surgery. STUDY DESIGN:
      Prospective case series study. SETTINGS: Tertiary referral center. PATIENTS:
      Forty-eight children ears without cholesteatoma were included in the study: 23
      with isolated pars tensa retraction (median age, 11), 25 with combined pars tensa
      and attic retractions (median age, 13). INTERVENTION(S): Otomicroscopy, pure tone
      audiometry, and impedancmetry were carried out preoperatively. Three surgical
      procedures for isolated retractions were used: ventilation tube insertion alone
      or together with fascia graft or cartilage graft. Two surgical procedures for
      combined retractions were used: ventilation tube insertion alone and with
      cartilage graft. MAIN OUTCOME MEASURES: Incidence of ossicular destruction,
      postoperative retraction of the grafts. RESULTS: Stage of pars tensa retraction
      and preoperative air conduction thresholds do not predict long incus process
      defect in isolated group. Coexistence of an attic retraction predicts combined,
      long incus process and stapes superstructure defect (Chi = 3.943, p = 0.047, OR =
      12.00). Retractions of grafts are predicted by mode of surgery, favoring
      cartilage graft (isolated group: Chi = 4.306, p = 0.0372,OR = 4.69; combined
      group Chi = 4.7836, p = 0.0287, OR = 0.1364). Stage of pars tensa retraction
      predicts poor outcome of fascia graft (Chi = 4.5347, p = 0.0332, OR = 12.00).
      CONCLUSION: Absence of correlation between stage of pars tensa retraction and air
      conduction thresholds with ossicular defects justifies surgical exploration of
      the auditory ossicles, even in lower stages of retraction. Combined ossicular
      defect is expected in combined retractions. The usage of cartilage graft proved
      to be more appropriate.

PMID- 24662636
TI  - Canal plane dynamic visual acuity in superior canal dehiscence.
AB  - OBJECTIVE: 1) To characterize normal, horizontal active dynamic visual acuity
      (DVA) and passive canal plane head thrust DVA (htDVA) across ages to establish
      appropriate control data and 2) to determine whether horizontal active DVA and
      passive canal plane htDVA are significantly different in individuals with
      superior canal dehiscence syndrome (SCDS) before and after surgical repair in the
      acute (within 10 d) and nonacute stage (>6 wk). STUDY DESIGN: Prospective study.
      SETTING: Tertiary referral center PATIENTS: Patients diagnosed with SCDS (n = 32)
      and healthy control subjects (n = 51). INTERVENTIONS: Surgical canal plugging on
      a subset of patients. MAIN OUTCOME MEASURES: Static visual acuity (SVA), active
      horizontal DVA, and canal plane htDVA. RESULTS: Visual acuity (SVA, active DVA,
      and htDVA) declines with age. In SCDS, SVA and active DVA are not significantly
      affected in individuals after surgical canal plugging; however, htDVA in the
      plane of the affected canal is significantly worse after canal plugging.
      CONCLUSION: Age-based normative data are necessary for DVA testing. In SCDS,
      htDVA in the plane of the affected canal is normal before surgery but permanently
      reduced afterward.

PMID- 24662637
TI  - Acquired atresia of the external auditory canal: long-term clinical and
      audiometric results after surgery.
AB  - OBJECTIVE: Acquired atresia of the external auditory canal is a rare condition in
      which the medial part of the external auditory canal is obliterated by a soft
      fibrous plug, mostly as a result of chronic inflammation of the outer ear canal.
      In this study, the clinical and audiometric long-term postsurgical results were
      assessed. PATIENTS: Records of patients with acquired atresia, surgically treated
      in a tertiary referral center during the period 2000-2009, were retrospectively
      reviewed. Preoperative and postoperative clinical and audiometric data were
      collected. INTERVENTION: All patients underwent the same surgical technique,
      consisting of a maximal bony canaloplasty with coverage of the bony ear canal
      using full-thickness skin graft and a meatoplasty. Eligible patients were
      reinvited for objective and subjective evaluation. MAIN OUTCOME MEASURES: The
      primary outcome was the long-term postoperative status, based on clinical
      (patency and condition of the external auditory canal) and audiometric findings
      (mean air-bone gap). RESULTS: The analysis comprised 17 operated ears (14
      different patients). Mean follow-up time was 5.14 years. True recurrence occurred
      in 3 ears (17.6%), whereas another 4 ears had episodic otorrhea (23.5%). At early
      (<0.5 yr), but also at late follow-up (>4y), the air-bone gap in the operated
      ears was significantly smaller. CONCLUSION: Surgical treatment for acquired
      atresia leads to beneficial results. Patients should be informed of the
      possibility of recurrence of disease. Nevertheless, they seem to be satisfied
      with the surgical intervention. Preoperative dermatologic referral is required,
      given the high prevalence of an underlying dermatologic disease.

PMID- 24662638
TI  - Willingness-to-accept Gamma knife radiosurgery for tinnitus among career San
      Francisco firefighters.
AB  - OBJECTIVE: Measure willingness-to-accept novel Gamma knife (GK) radiosurgery of
      the caudate nucleus to treat tinnitus among career firefighters who are at higher
      risk of hearing loss because of occupational noise exposure. STUDY DESIGN: Cross
      sectional survey. MATERIALS AND METHODS: A Web-based 80-item survey was
      distributed to 800 San Francisco firefighters and satisfactorily completed by 101
      respondents. Demographic and work-related characteristics including occupational
      noise exposure, hearing handicap using the Hearing Handicap Inventory for Adults
      (HHIA), and tinnitus severity using the tinnitus functional index (TFI) were
      assessed. Willingness-to-accept GK radiosurgery for tinnitus was profiled using a
      7-point scale for 6 decremental levels of expected tinnitus improvement. RESULTS:
      Respondents were a majority male (82%) and Caucasian (56%). Nearly all (95%)
      reported significant daily or weekly occupational noise exposure. Mean HHIA
      (16.3) and mean TFI (14.6) were mild. At the 100% (complete) tinnitus improvement
      level, more than 60% of respondents were "likely" willing-to-accept Gamma knife
      radiosurgery. At the 75% tinnitus improvement level, 43% of respondents were
      "likely" willing-to-accept GK radiosurgery. Below the 75% tinnitus improvement
      level, willingness-to-accept dropped off steeply. CONCLUSION: Gamma knife
      radiosurgery to area LC, a locus of the caudate nucleus, for tinnitus would be of
      interest to a large population with moderate or lower tinnitus distress. Should
      this innovative intervention be considered in the future, a rigorous clinical
      trial will be necessary to establish safety and efficacy.

PMID- 24662639
TI  - Impedance, neural response telemetry, and speech perception outcomes after
      reimplantation of cochlear implants in children.
AB  - OBJECTIVE: To compare mean impedance levels, neural response telemetry (NRT), and
      auditory perception after initial and explant-reimplant pediatric cochlear
      implants. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral
      hospital and cochlear implant program. PATIENTS: Children 0 to 16 years inclusive
      who have undergone explant-reimplant of their cochlear implant. INTERVENTION:
      Impedance levels, NRT, and speech perception performance. MAIN OUTCOME MEASURES:
      Impedance, NRT, and auditory perception at switch on, 3 months, 12 months, 3
      years, and 5 years after initial cochlear implant and reimplantation. RESULTS:
      The explant-reimplant group receiving Cochlear contour array had significantly (p
      < 0.001) raised impedance at switch on, 3 months, 12 months, and 3 years,
      compared with their initial implant. The explant-reimplant group receiving
      Cochlear straight array had marginally significant (p = 0.045) raised impedance
      at switch on, 3 months, 12 months, and 3 and 5 years. Infection was associated
      with greater increases in impedance in the reimplant Contour group. NRT was
      increased in the explant-reimplant group but not significantly (p = 0.06).
      Auditory perception returned to preexplant levels within 6 months in 61% of
      children. CONCLUSION: Impedance is higher after explant-reimplant and remains
      increased for years after explant-reimplant with Cochlear contour and to a lesser
      degree the straight array device.

PMID- 24662640
TI  - The individual and socioeconomic impact of osteoarthritis.
AB  - Osteoarthritis (OA) is a highly prevalent, disabling disease, with a commensurate
      tremendous individual and socioeconomic burden. This Perspectives article focuses
      on the burden of OA for the individual, the health-care system and society, to
      draw attention to the magnitude of the current problem with some reference to
      projected figures. We have an urgent opportunity to make fundamental changes to
      the way we care for individuals with OA that will have an effect upon the direct
      and indirect costs of this disease. By focusing on the burden of this prevalent,
      disabling, and costly disease, we hope to highlight the opportunity for shifts in
      health-care policy towards prevention and chronic-disease management.

PMID- 24662644
TI  - Fibromyalgia: Honing fibromyalgia diagnosis.

PMID- 24662646
TI  - Dual ectopic thyroid gland: sonography and scintigraphy of lingual and sublingual
      thyroid.
AB  - Dual ectopic lingual and sublingual thyroid gland is an extraordinarily rare
      condition. We present 1 patient with subclinical hypothyroidism. The clinical
      examination revealed that the thyroid gland was not palpable in its usual
      cervical location, whereas ultrasonography confirmed an empty thyroid bed without
      any ectopic thyroid tissue in the rest of the neck. The final diagnosis of dual
      ectopic lingual and sublingual thyroid was established by ultrasound examination
      through the mouth floor and confirmed by scintigraphy and CT thereafter. 

PMID- 24662647
TI  - Changes in (99m)Tc-ECD SPECT and magnetic resonance angiography with sporadic
      hemiplegic migraine in a child.
AB  - Sporadic hemiplegic migraine is rare in childhood. We followed a patient with Tc
      ECD (Tc-ethyl cysteinate dimer) SPECT and magnetic resonance angiography (MRA).
      At the age of 8 years, he developed left hemiplegia. The MRA showed
      vasoconstriction of the posterior right middle cerebral artery. Hemiplegia
      disappeared in a few hours, and the MRA normalized. At the age of 10 years, right
      hemiplegia was observed, disappearing completely after a few days. During this
      second migraine attack, MRA demonstrated left middle cerebral artery
      vasoconstriction, and SPECT revealed decreased left hemisphere blood flow.
      Findings normalized as the patient recovered. 

PMID- 24662645
TI  - Mouse models of osteoarthritis: modelling risk factors and assessing outcomes.
AB  - Osteoarthritis (OA) is a prevalent musculoskeletal disease that results in pain
      and low quality of life for patients, as well as enormous medical and
      socioeconomic burdens. The molecular mechanisms responsible for the initiation
      and progression of OA are still poorly understood. As such, mouse models of the
      disease are having increasingly important roles in OA research owing to the
      advancements of microsurgical techniques and the use of genetically modified
      mice, as well as the development of novel assessment tools. In this Review, we
      discuss available mouse models of OA and applicable assessment tools in studies
      of experimental OA. 

PMID- 24662648
TI  - Ocular sarcoidosis: does (18)F-FDG PET/CT have any role?
AB  - Sarcoidosis is a multisystemic disease, which may affect almost any organ
      including the eyes. Recently, F-FDG PET/CT has proved to be a very useful
      molecular imaging method allowing to obtain a complete morphofunctional
      cartography of active inflammatory sites and to assess treatment response in
      patients with sarcoidosis. We report 2 cases of sarcoidosis where F-FDG PET/CT
      showed intense FDG uptake in the eye globes along with multiple enlarged
      mediastinal lymph nodes suggestive of active sarcoidosis with ocular involvement.

PMID- 24662649
TI  - Appearance of recurrent cardiac myxofibrosarcoma on FDG PET/CT.
AB  - Primary cardiac sarcomas are extremely rare tumors. In this case report, we
      presented the condition of a 37-year-old male patient diagnosed with
      myxofibrosarcoma after histopathologic evaluation of the left atrium mass
      excision. FDG PET/CT was performed and showed recurrent hypermetabolic lesions in
      the left atrial wall and right anterior mediastinal region. 

PMID- 24662650
TI  - (67)Ga SPECT/CT accurately localized recurrent hepatic cyst infection in patients
      with autosomal dominant polycystic kidney disease.
AB  - Hepatic pyocyst is a rare but potentially life-threatening complication of
      autosomal dominant polycystic kidney disease. With extensive hepatic cystic
      disease, localization of a pyocyst and targeted aspiration or drainage is often a
      diagnostic challenge. Two patients with autosomal dominant polycystic kidney
      disease and recurrent gram-negative sepsis were imaged with Ga SPECT/CT for
      investigation of an infective source. In both patients, imaging accurately
      localized infected pyocysts and guided percutaneous drainage and further
      management. 

PMID- 24662651
TI  - Illustration of protein loss from the stomach by using SPECT/CT: a case of
      Menetrier disease.
AB  - We report a 47-year-old man in whom Tc human serum albumin diethylene-triamine
      pentaacetic acid protein-losing scintigraphy, performed with SPECT/CT, was useful
      for diagnosing Menetrier disease. Planar images taken 1 and 3 hours after
      radioactive isotope injection yielded a suspicion that the stomach was the site
      of protein loss in this case. However, the protein loss from the stomach was
      precisely diagnosed after SPECT/CT was performed; this helped to diagnose
      Menetrier disease. 

PMID- 24662652
TI  - Diagnostic utility of (18)F-FDG PET/CT in inflammation of unknown origin.
AB  - OBJECTIVES: The goal of this multicenter retrospective study was to evaluate the
      contribution of F-FDG PET/CT in the diagnosis of patients with inflammation of
      unknown origin (IUO). In addition, C-reactive protein (CRP) level and erythrocyte
      sedimentation rate were assessed as possible predictors for the outcome of F-FDG
      PET/CT. METHODS: Inflammation of unknown origin was defined as prolonged and
      perplexing inflammation, with repeated CRP levels more than 20 mg/L or
      erythrocyte sedimentation rate more than 20 mm/h, body temperature of less than
      38.3 degrees C, and without a diagnosis after a variety of conventional
      diagnostic procedures.A total of 140 patients with IUO (67 men, 73 women; mean
      age, 64.2 years; age range, 18-87 years) underwent F-FDG PET/CT. F-FDG PET/CT was
      considered helpful when the imaging findings led to a diagnosis, either confirmed
      by histopathology, microbiological assays, clinical and imaging follow-up, or
      response to treatment. RESULTS: In 104 patients (73%), a final diagnosis could be
      established as follows: infection in 35 patients, malignancy in 18 patients,
      noninfectious inflammatory disease in 44 patients, and a variety of uncommon
      conditions in 7 patients. F-FDG PET/CT was true positive in 95 patients, true
      negative in 30 patients (ie, self-limiting conditions), false positive in 6
      patients, and false negative in 9 patients (predominantly systemic diseases). In
      this population, the positive predictive value, negative predictive value, and
      diagnostic accuracy of F-FDG PET/CT were 94%, 77%, and 89%, respectively. In a
      multivariate analysis, CRP was the only independent predictor for the outcome of
      F-FDG PET/CT. CONCLUSIONS: F-FDG PET/CT correctly identified or excluded a causal
      explanation in approximately 90% of patients with IUO. However, a negative F-FDG
      PET/CT is indicative for a self-limiting condition only after systemic diseases
      are excluded by other diagnostic tests.

PMID- 24662653
TI  - Differentiation of an unclear splenic lesion in a patient with
      cholangiocarcinoma.
AB  - Here we report on a 51-year-old man with the primary diagnosis of
      cholangiocarcinoma. Workup with CT and contrast-enhanced ultrasound revealed an
      additional lesion in the spleen, raising the concern for metastasis. Combined FDG
      PET/CT revealed a different metabolic pattern, making a metastasis unlikely.
      Histopathology of the splenic lesion confirmed sclerosing angiomatoid nodular
      transformation, a rare benign lesion of the spleen. 

PMID- 24662654
TI  - Unilateral breast uptake on radionuclide ventriculography.
AB  - Gated equilibrium radionuclide ventriculography is frequently used to measure the
      left ventricular ejection fraction. We report a case of unilateral breast
      activity resulting in significant underestimation of the left ventricular
      ejection fraction, which mimicked a left ventricular aneurysm, pseudoaneurysm, or
      an intrathoracic vascular mass. Unilateral breast uptake, in the absence of
      gastric activity, was presumed because of increased blood pool in the lactating
      breast, a finding not previously reported in the literature. This case is also
      presented to emphasize the importance of localizing abnormalities based on a
      review of tomographic images or images taken in at least 2 orthogonal
      projections. 

PMID- 24662655
TI  - A rare presentation of myocardial plasmacytoma assessed by FDG PET/CT.
AB  - We describe a rare case of myocardial plasmacytoma staged and followed up with
      FDG PET/CT. A 72-year-old man was incidentally identified with a right
      ventricular apical mass, which was pathologically confirmed to be a plasmacytoma.
      A pre-treatment FDG PET/CT scan subsequently showed lesions not only in the right
      ventricle but also in the bones and mediastinal lymph nodes, which led to the
      change in treatment plan. Post-therapy PET scan revealed good response. This case
      demonstrates the value of FDG PET/CT in accurately staging unusually presented
      plasmacytoma and in monitoring response to treatment. 

PMID- 24662656
TI  - Unilateral physiological FDG uptake in teres minor muscle seems well associated
      with IV tracer injection procedures.
AB  - FDG uptake in teres minor (TM) muscle is often physiologically observed. Here we
      reviewed data of 578 consecutive patients; TM uptake was observed in 138 patients
      in 2 of 68 patients who were administered with FDG via a preexisting line and in
      136 of 510 after on-site puncture. In 126 patients with TM uptake without
      unsuccessful on-site puncture, 78% of TM uptake sites were on the ipsilateral
      side of injection, 8% on the contralateral side, and 14% on both sides; Cohen
      kappa coefficient was 0.815 when confined to unilateral uptake. Therefore, TM
      uptake seems well associated with tracer injection procedures. 

PMID- 24662657
TI  - Somatostatin receptor-positive granulomatous inflammation mimicking as meningioma
      on simultaneous PET/MRI.
AB  - Positron imaging with radiolabeled synthetic somatostatin receptor analogs such
      as Ga DOTATATE (Gallium-68-1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetra
      acetic acid-DPhe1,Tyr3-octreotate) is used for diagnosis and target volume
      delineation of intracranial meningiomas. We report a case of a somatostatin
      receptor-positive extra-axial necrotizing granulomatous inflammation mimicking as
      meningioma on simultaneous Ga DOTATATE PET/MRI. This case illustrates a Ga
      DOTATATE-positive granuloma bearing a striking resemblance to meningioma. 

PMID- 24662658
TI  - Bruxism--before and after images--on 18F-FDG PET/CT.
AB  - Physical activity before F-FDG PET/CT can cause increased muscle glucose
      metabolism. We report markedly increased glucose metabolism in the masseter and
      temporalis muscles of a 53-year-old man who was clenching his teeth before the
      scan, and then resolution of this increased metabolism on a second scan 12 weeks
      later. SUVmax in the right masseter muscle was 26.9; 12 weeks later, the SUVmax
      was 1.6. This level of FDG uptake in bruxism has not yet been reported. 

PMID- 24662659
TI  - 18F-FDG hepatic superscan in a patient with chronic myeloid leukemia.
AB  - A 62-year-old man with a history of breakpoint cluster region-ABL-positive
      chronic myeloid leukemia treated with hydroxyurea and interferon alfa for 4 years
      presented a lesion in the left lateral lobe of the liver. Besides an FDG-avid
      lesion, his 18F-FDG PET/CT study showed intense and diffuse FDG uptake
      (reminiscent of a hepatic superscan) throughout the rest of the left lobe and the
      right anterior lobe of the liver. This interesting superscan indicated that
      patients with chronic myeloid leukemia may show hepatic involvement by leukemia
      cells.

PMID- 24662660
TI  - 18F-FDG PET as a monitoring tool to assess treatment response in bilateral
      adrenal histoplasmosis.
AB  - A 60-year-old woman with clinical and biochemical features suggestive of adrenal
      insufficiency was found to have bilateral adrenal masses on CT scan and was
      subjected to F-FDG PET scan. The scan showed hypermetabolic mediastinal nodes in
      addition to intense tracer uptake in bilateral adrenal masses. CT-guided adrenal
      biopsy grew Histoplasma capsulatum on Sabouraud dextrose agar culture. A second F
      FDG PET scan after 6 months of appropriate antifungal therapy showed a
      significant decrease in intensity of uptake consistent with the clinical outcome.

PMID- 24662661
TI  - Sphenoid wing meningioma behavior on 11C-PiB and 18F-FDG PET.
AB  - Two patients with mild cognitive impairment underwent C-PiB and F-FDG brain PET.
      Both patients had previously gone through a contrast-enhanced MRI scan that
      revealed extra-axial tumors next to the sphenoid wing, suggestive of meningiomas.
      C-PiB PET images showed a highly increased uptake by the extra-axial masses.
      These 2 cases represent 1.2% of our C-PiB population (n = 163). No meningioma was
      found with negative C-PiB uptake. The F-FDG concentration was not increased
      within the lesions. C-PiB could be used as a meningioma marker. 

PMID- 24662662
TI  - The ratio of (18)F-FDG activity uptake between the right and left ventricle in
      patients with pulmonary hypertension correlates with the right ventricular
      function.
AB  - PURPOSE: It is known that patients with pulmonary hypertension (PH) can have
      elevated F-FDG uptake in the right ventricle (RV) on PET imaging. This study was
      designed to assess possible relationship between FDG uptake of ventricles and the
      function/hemodynamics of the RV in patients with PH. PATIENTS AND METHODS: Thirty
      eight patients with PH underwent FDG PET imaging in both fasting and glucose
      loading conditions. The standard uptake value (SUVs) corrected for partial volume
      effect in both RV and left ventricle (LV) were measured. The ratio of FDG uptake
      between RV to LV (SUVR/L) was calculated. Right heart catheterization and cardiac
      magnetic resonance (CMR) were performed in all patients within 1 week. The FDG
      uptake levels by the ventricles were compared with the result form the right
      heart catheterization and CMR. RESULTS: The SUV of RV (SUVR) and SUV of LV were
      significantly higher in glucose-loading condition than in fasting condition. In
      both fasting and glucose-loading conditions, SUVR and SUVR/L showed reverse
      correlation with right ventricular ejection fraction derived from CMR. In
      addition, in both fasting and glucose-loading conditions, SUVR and SUVR/L showed
      positive correlations with pulmonary vascular resistance. However, only SUVR/L in
      glucose-loading condition could independently predict right ventricular ejection
      fraction after adjusted for age, body mass index, sex, mean right atrial
      pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (P
      = 0.048). CONCLUSIONS: The FDG uptake of RV increases with decreased right
      ventricular function in patients with PH. Increased FDG uptake ratio between RV
      and LV might be useful to assess the right ventricular function.

PMID- 24662663
TI  - Tips for a physician in getting the right job, part XI: important things to do
      for an interview.
AB  - There are many important things for the applicant to remember to do during an
      interview. It is important for the job seeker to be well rested for the interview
      and to arrive on time. The candidate should be positive, show enthusiasm and high
      energy, be respectful and friendly, smile, be brief and to the point in answers,
      not embellish his/her qualifications, and be candid in all responses. The answers
      should be delivered in a clearly heard voice, with reasonable speed, and in
      varying tone. 

PMID- 24662665
TI  - Preoperative FDG PET/CT in adrenocortical cancer depicts massive venous tumor
      invasion.
AB  - A 79-year-old woman presented with abdominal pain. Ultrasound revealed an intra
      abdominal mass in the left renal region. Comprehensive endocrine workup was
      unremarkable. The patient was referred for further diagnostic workup. FDG PET/CT
      revealed a hypermetabolic mass in the left adrenal region. In addition,
      pathologically increased tracer uptake of 2 renal veins (the upper vein crossing
      in front of the aorta the lower one crossing behind the aorta) and the inferior
      vena cava raised the concern for malignant venous infiltration. Adrenalectomy,
      nephrectomy, and thrombectomy were carefully planned and performed.
      Adrenocortical carcinoma with tumor thrombus and caval extension was proven by
      histopathology. 

PMID- 24662664
TI  - A case of olfactory neuroblastoma detected by (18)F-FDG PET/CT.
AB  - Olfactory neuroblastoma is an uncommon malignant neoplasm of the superior nasal
      cavity. We report a case of a 78-year-old woman who presented with frontal
      headache and proptosis of the right eye. CT revealed a nasoethmoid mass with
      diffuse calcifications. FDG PET/CT demonstrated intense FDG uptake by a main
      nasoethmoid tumor and metastatic lesions in the cervical lymph nodes. Histologic
      examination confirmed olfactory neuroblastoma. 

PMID- 24662666
TI  - Squamous cell carcinoma of the tonsil incidentally detected by 18F-choline
      PET/CT.
AB  - We report a case of squamous cell carcinoma of the tonsil incidentally detected
      by F-choline PET/CT. A 55-year-old male patient with a history of prostate cancer
      underwent F-choline PET/CT for restaging. PET/CT revealed a focal area of
      increased F-choline uptake corresponding to the left tonsil. No other areas of
      abnormal F-choline uptake were detected in the rest of the body. Based on these
      PET/CT findings, the patient underwent clinical examination and biopsy of the
      left tonsil. Histology demonstrated the presence of a squamous cell carcinoma of
      the tonsil. 

PMID- 24662667
TI  - Detecting near-the-injection-site sentinel nodes in head and neck melanomas with
      a high-resolution portable gamma camera.
AB  - BACKGROUND: In head/neck melanomas, near-the-injection-site sentinel nodes (NIS
      SNs) may be missed on planar lymphoscintigraphy and/or SPECT/CT. The aim of the
      present study is to establish the performance of a portable gamma camera (PGC) to
      detect NIS-SNs in a simulation phantom set-up, and subsequently in head/neck
      melanoma patients scheduled for a SN procedure. METHODS: Five plastic Eppendorf
      tubes filled with technetium-99m-albumin nanocolloid were used to simulate 4
      radiotracer deposit sites, as traditionally injected in melanoma patients, and 1
      NIS-SN. A PGC was used with 2 pinhole collimators (2.5 and 4.0 mm). Image
      acquisition time was 1 minute with the camera positioned at various distances
      (range 1.5-15.5 cm). Results were compared with conventional lymphoscintigraphy
      and SPECT/CT acquired with a dual-head gamma camera as well with a gamma probe.
      Additionally, the same PGC setting was used in a case series of 3 patients with
      head/neck melanomas. RESULTS: The simulated NIS-SN was differentiated from the
      injection site at a distance of 3 mm with the 2.5-mm pinhole and at 5 mm with the
      4-mm pinhole when the PGC was positioned at 1.5 cm distance. Planar
      lymphoscintigraphy, SPECT/CT, and the gamma probe depicted the NIS-SN separated
      from the injection site at distances of 7, 10, and 22 mm, respectively. In all 3
      patients, 6 NIS-SNs were depicted with the PGC. CONCLUSION: A high-resolution
      PGC, positioned close to the skin, is able to detect SNs at distances of at least
      3 mm from the injection site. A further clinical evaluation of this device to
      establish its added value in reducing false-negative procedures and potential
      recurrences is necessary.

PMID- 24662668
TI  - Somatostatin receptor imaging in non-(131)I-avid metastatic differentiated
      thyroid carcinoma for determining the feasibility of peptide receptor
      radionuclide therapy with (177)Lu-DOTATATE: low fraction of patients suitable for
      peptide receptor radionuclide therapy and evidence of chromogranin A level
      positive neuroendocrine differentiation.
AB  - OBJECTIVE: The aim of the study was to evaluate somatostatin receptor expression
      in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE
      PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE
      (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC
      TOC scintigraphy. METHODS: In this research study, 19 patients diagnosed with
      differentiated thyroid carcinoma with non-iodine-concentrating metastasis with
      elevated serum thyroglobulin levels, attending thyroid outpatient department for
      follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of
      positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR
      positive lesions were graded into 4 categories (grades I-IV) in comparison with
      the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions
      (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE
      administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from
      the isolation ward. RESULTS: Of the 19 patients studied, 12 patients (63%) showed
      SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and
      7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific
      analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I
      tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%)
      grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than
      liver). Interestingly, an elevated serum chromogranin A level was documented in 3
      of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE
      PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated
      no significant differences in the tracer concentration in the metastatic lesions
      in any of the patients on visual grading. Based on the criterion of high tracer
      uptake and the patient consent, finally 2 of 3 patients were treated with Lu
      DOTATATE. On follow-up after 3 months, a significant fall in serum thyroglobulin
      level was noted in one of the patients, and the other patient was lost to follow
      up. CONCLUSIONS: Avid expression of the SSTR on Ga-DOTATATE PET-CT/Tc-HYNIC-TOC
      scintigraphy in non-I-concentrating metastatic differentiated thyroid cancer is
      observed in a relatively low fraction of patients that could favor the
      feasibility of Lu-DOTATATE therapy. Although seen in a small fraction, taking
      into account that no treatment exists in this group, somatostatin receptor
      targeted imaging can be an alternative diagnostic modality in the therapeutic
      decision making with peptide receptor radionuclide therapy and monitoring. The
      documentation of elevated serum chromogranin A level in 3 patients with intense
      tracer uptake could suggest a possible neuroendocrine differentiation in the
      affected tissues leading to the expression of chromogranin A along with SSTR-avid
      expression. This observation needs to be explored in future studies. No definite
      conclusions can be drawn on the therapeutic efficacy of the Lu-DOTATATE therapy
      in this group at present, and more prospective research is required in this area.

PMID- 24662669
TI  - Detection of early esophageal cancer and cervical lymph node metastases by (18)F
      FDG PET/CT in a patient with Fanconi anemia.
AB  - Fanconi anemia is a rare autosomal recessive disease characterized by multiple
      congenital anomalies, pancytopenia, and cancer susceptibility, especially to
      leukemia and squamous cell carcinoma of the head and neck or esophagus. F-FDG
      PET/CT is a useful tool to assess tumor staging and follow-up of esophageal
      cancer. We report a rare case of cervical esophageal cancer and lymph node
      metastases detected on F-FDG PET/CT in a patient with Fanconi anemia after bone
      marrow transplantation. 

PMID- 24662670
TI  - A successful experience in managing a chylous reflux: importance of
      lymphoscintigraphy.
AB  - Chylous reflux is described as the backflow of chyle through the varicose
      lymphatics with incompetent lymph valves and leakage of the lymph. The valves in
      the dilated, varicose, tortuous lymph vessels become incompetent, and as a
      result, the lymph blended with chyle, reflux into the lower limbs or the
      genitalia. Reflux causes delayed lymphatic transport in the affected lower
      extremity and chronic lymphedema can develop. Vesicles containing chyle could
      appear on the skin of the involved parts, and milky fluid discharge of the lymph
      and chyle interferes greatly with quality of life. 

PMID- 24662671
TI  - Concurrent rho-kinase and tyrosine kinase platelet-derived growth factor
      inhibition in experimental pulmonary hypertension.
AB  - BACKGROUND: We hypothesized that inhibition of Rho-kinase by fasudil, together
      with tyrosine kinase platelet-derived growth factor (PDGF) receptor inhibition by
      imatinib, results in greater pulmonary arterial hypertension (PAH) improvement.
      METHODS: The effects of such regimens were investigated on hemodynamics, right
      ventricle hypertrophy, PDGF and ROCK in experimental monocrotaline (MCT)-induced
      pulmonary hypertension. Fourteen days after MCT injection, male rats were treated
      orally for another 14 days with imatinib, fasudil or their combination. RESULTS:
      Concurrent imatinib and fasudil administration reversed an MCT-induced increase
      in right ventricular pressure more than either drug alone and decreased right
      ventricle hypertrophy (right ventricle weight to left ventricle plus septum
      weight ratio) significantly. The simultaneous administration of fasudil and
      imatinib caused a further decrease in plasma PDGF-BB levels compared to either
      drug alone. CONCLUSIONS: Inhibition of Rho-kinase by fasudil in addition to
      tyrosine kinase PDGF inhibition by imatinib can result in further PAH
      improvement. Such outcome may result from additional impact of the Rho-kinase
      inhibitor on the decrease in PDGF-induced effects.

PMID- 24662672
TI  - Quantification of trabectedin in human plasma: validation of a high-performance
      liquid chromatography-mass spectrometry method and its application in a clinical
      pharmacokinetic study.
AB  - A rapid, sensitive and specific HPLC-MS/MS method was developed and validated for
      the quantification of trabectedin in human plasma after using deuterated
      trabectedin as Internal Standard (IS). After the addition of ammonium sulphate,
      the analyte was extracted from human plasma with acidified methanol (0.1 M HCl).
      Chromatographic separation was done on an Accucore XL C18 column (4 MUm; 50 mm *
      2.1 mm) using a Mobile Phase (MP) consisting of CH3COONH4 10 mM, pH 6.8 (MP A)
      and CH3OH (MP B). The mass spectrometer worked with electrospray ionization in
      positive ion mode and Selected Reaction Monitoring (SRM), using target ions at [M
      H2O+H]+ m/z 744.4 for trabectedin and [M-H2O+H]+m/z 747.5 for the IS. The
      standard curve was linear (R2 >= 0.9955) over the concentration range 0.025-1.0
      ng/ml and had good back-calculated accuracy and precision. The intra- and inter
      day precision and accuracy determined on three quality control samples (0.04,
      0.08 and 0.80 ng/ml) were <9.9% and between 98.3% and 105.3%, respectively. The
      extraction recovery was >81% and the lower limit of quantification 0.025 ng/ml.
      The method was successfully applied to study trabectedin pharmacokinetics in a
      patient with a liposarcoma who received 1.3 mg/m2 as a 24 h continuous i.v.
      infusion.

PMID- 24662673
TI  - Single-dose intranasal treatment with DEF201 (adenovirus vectored consensus
      interferon) prevents lethal disease due to Rift Valley fever virus challenge.
AB  - Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The
      virus can be transmitted by mosquitoes, direct contact with infected tissues or
      fluids, or aerosol, making it a significant biological threat for which there is
      no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201,
      an adenovirus-vectored interferon alpha which addresses the limitations of
      recombinant interferon alpha protein (cost, short half-life), as a pre- and post
      exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered
      intranasally to stimulate mucosal immunity and effectively bypass any pre
      existing immunity to the vector. Complete protection against RVFV infection was
      observed from a single dose of DEF201 administered one or seven days prior to
      challenge while all control animals succumbed within three days of infection.
      Efficacy of treatment administered two weeks prior to challenge was limited. Post
      exposure, DEF201 was able to confer significant protection when dosed at 30 min
      or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with
      reductions in serum and tissue viral loads. Our findings suggest that DEF201 may
      be a useful countermeasure against RVFV infection and further demonstrates its
      broad-spectrum capacity to stimulate single dose protective immunity. 

PMID- 24662674
TI  - IFN-dependent and -independent reduction in West Nile virus infectivity in human
      dermal fibroblasts.
AB  - Although dermal fibroblasts are one of the first cell types exposed to West Nile
      virus (WNV) during a blood meal by an infected mosquito, little is known about
      WNV replication within this cell type. Here, we demonstrate that neuroinvasive,
      WNV-New York (WNV-NY), and nonneuroinvasive, WNV-Australia (WNV-AUS60) strains
      are able to infect and replicate in primary human dermal fibroblasts (HDFs).
      However, WNV-AUS60 replication and spread within HDFs was reduced compared to
      that of WNV-NY due to an interferon (IFN)-independent reduction in viral
      infectivity early in infection. Additionally, replication of both strains was
      constrained late in infection by an IFN-beta-dependent reduction in particle
      infectivity. Overall, our data indicates that human dermal fibroblasts are
      capable of supporting WNV replication; however, the low infectivity of particles
      produced from HDFs late in infection suggests that this cell type likely plays a
      limited role as a viral reservoir in vivo. 

PMID- 24662675
TI  - Retrospective serology study of respiratory virus infections in captive great
      apes.
AB  - Great apes are extremely sensitive to infections with human respiratory viruses.
      In this study, we retrospectively analyzed sera from captive chimpanzees,
      gorillas and orang-utans. More than 1000 sera (403 chimpanzee, 77 gorilla, and
      535 orang-utan sera) were analyzed for antibodies to the human respiratory
      viruses RSV (respiratory syncytial virus, hMPV (human metapneumovirus), H1N1 and
      H3N2 influenza A viruses, and influenza B virus. In all ape species high
      seroprevalences were found for RSV, hMPV, and influenza B virus. A high
      percentage of captive chimpanzees also showed evidence of influenza A H1N1
      infections, and had low levels of H3N2 antibodies, while in sera from gorillas
      and orangutans antibody levels to influenza A and B viruses were much lower or
      practically absent. Transmission of respiratory viruses was examined in
      longitudinal sera of young chimpanzees, and in chimpanzee sera taken during
      health checks. In young animals isolated cases of influenza infections were
      monitored, but evidence was found for single introductions followed by a rapid
      dissemination of RSV and hMPV within the group. Implementation of strict
      guidelines for handling and housing of nonhuman primates was shown to be an
      efficient method to reduce the introduction of respiratory infections in colonies
      of captive animals. RSV seroprevalence rates of chimpanzees remained high,
      probably due to circulating virus in the chimpanzee colony.

PMID- 24662677
TI  - Error and performance feedback processing by children with Specific Language
      Impairment--an ERP study.
AB  - The study evaluates error and feedback related processing in children with
      Specific Language Impairment (SLI), and in age and gender matched controls.
      Participants performed two tasks which varied in the extent to which feedback was
      provided following each response. Although no group differences were found in
      accuracy and response time measures, children with SLI corrected a smaller
      proportion of their errors in comparison with the control group.
      Neurophysiological data pointed to error and feedback processing differences
      between the two groups. Errors committed by the control group elicited error
      related ERP components (ERN, Pe), while these components were attenuated in the
      SLI group. A posterior positivity was elicited in association with incorrect
      responses in both groups. When a feedback stimulus informed the participants
      about the accuracy of the response, the feedback, rather than the response,
      elicited an ERN in the control group, while no ERN was elicited in the SLI group.
      These results suggest that children with SLI have an impaired ability to self
      monitor performance and to take advantage of performance feedback. 

PMID- 24662678
TI  - Hydride ions in oxide hosts hidden by hydroxide ions.
AB  - The true oxidation state of formally 'H(-)' ions incorporated in an oxide host is
      frequently discussed in connection with chemical shifts of (1)H nuclear magnetic
      resonance spectroscopy, as they can exhibit values typically attributed to H(+).
      Here we systematically investigate the link between geometrical structure and
      chemical shift of H(-) ions in an oxide host, mayenite, with a combination of
      experimental and ab initio approaches, in an attempt to resolve this issue. We
      demonstrate that the electron density near the hydrogen nucleus in an OH(-) ion
      (formally H(+) state) exceeds that in an H(-) ion. This behaviour is the opposite
      to that expected from formal valences. We deduce a relationship between the
      chemical shift of H(-) and the distance from the H(-) ion to the coordinating
      electropositive cation. This relationship is pivotal for resolving H(-) species
      that are masked by various states of H(+) ions. 

PMID- 24662676
TI  - A role for CD81 and hepatitis C virus in hepatoma mobility.
AB  - Tetraspanins are a family of small proteins that interact with themselves, host
      transmembrane and cytosolic proteins to form tetraspanin enriched microdomains
      (TEMs) that regulate important cellular functions. Several tetraspanin family
      members are linked to tumorigenesis. Hepatocellular carcinoma (HCC) is an
      increasing global health burden, in part due to the increasing prevalence of
      hepatitis C virus (HCV) associated HCC. The tetraspanin CD81 is an essential
      receptor for HCV, however, its role in hepatoma biology is uncertain. We
      demonstrate that antibody engagement of CD81 promotes hepatoma spread, which is
      limited by HCV infection, in an actin-dependent manner and identify an essential
      role for the C-terminal interaction with Ezrin-Radixin-Moesin (ERM) proteins in
      this process. We show enhanced hepatoma migration and invasion following
      expression of CD81 and a reduction in invasive potential upon CD81 silencing. In
      addition, we reveal poorly differentiated HCC express significantly higher levels
      of CD81 compared to adjacent non-tumor tissue. In summary, these data support a
      role for CD81 in regulating hepatoma mobility and propose CD81 as a tumour
      promoter. 

PMID- 24662679
TI  - Update in pediatric infective endocarditis.

PMID- 24662680
TI  - Each flying fox on its own branch: a phylogenetic tree for Pteropus and related
      genera (Chiroptera: Pteropodidae).
AB  - Pteropodidae is a diverse Old World family of non-echolocating, frugivorous and
      nectarivorous bats that includes the flying foxes (genus Pteropus) and allied
      genera. The subfamily Pteropodinae includes the largest living bats and is
      distributed across an immense geographic range from islands in East Africa to the
      Cook Islands of Polynesia. These bats are keystone species in their ecosystems
      and some carry zoonotic diseases that are increasingly a focus of interest in
      biomedical research. Here we present a comprehensive phylogeny for pteropodines
      focused on Pteropus. The analyses included 50 of the ~63 species of Pteropus and
      11 species from 7 related genera. We obtained sequences of the cytochrome b and
      the 12S rRNA mitochondrial genes for all species and sequences of the nuclear
      RAG1, vWF, and BRCA1 genes for a subsample of taxa. Some of the sequences of
      Pteropus were obtained from skin biopsies of museum specimens including that of
      an extinct species, P. tokudae. The resulting trees recovered Pteropus as
      monophyletic, although further work is needed to determine whether P. personatus
      belongs in the genus. Monophyly of the majority of traditionally-recognized
      Pteropus species groups was rejected, but statistical support was strong for
      several clades on which we based a new classification of the Pteropus species
      into 13 species groups. Other noteworthy results emerged regarding species status
      of several problematic taxa, including recognition of P. capistratus and P.
      ennisae as distinct species, paraphyly of the P. hypomelanus complex, and
      conspecific status of P. pelewensis pelewensis and P. p. yapensis. Relationships
      among the pteropodine genera were not completely resolved with the current
      dataset. Divergence time analysis suggests that Pteropus originated in the
      Miocene and that two independent bursts of diversification occurred in the
      Pleistocene in different regions of the Indo-Pacific realm.

PMID- 24662681
TI  - Shedding subspecies: The influence of genetics on reptile subspecies taxonomy.
AB  - The subspecies concept influences multiple aspects of biology and management. The
      'molecular revolution' altered traditional methods (morphological traits) of
      subspecies classification by applying genetic analyses resulting in alternative
      or contradictory classifications. We evaluated recent reptile literature for bias
      in the recommendations regarding subspecies status when genetic data were
      included. Reviewing characteristics of the study, genetic variables, genetic
      distance values and noting the species concepts, we found that subspecies were
      more likely elevated to species when using genetic analysis. However, there was
      no predictive relationship between variables used and taxonomic recommendation.
      There was a significant difference between the median genetic distance values
      when researchers elevated or collapsed a subspecies. Our review found nine
      different concepts of species used when recommending taxonomic change, and
      studies incorporating multiple species concepts were more likely to recommend a
      taxonomic change. Since using genetic techniques significantly alter reptile
      taxonomy there is a need to establish a standard method to determine the species
      subspecies boundary in order to effectively use the subspecies classification for
      research and conservation purposes. 

PMID- 24662682
TI  - Measuring quantum coherence in bulk solids using dual phase-locked optical
      pulses.
AB  - Electronic and phonon coherence are usually measured in different ways because
      their time-scales are very different. In this paper we simultaneously measure the
      electronic and phonon coherence using the interference of the electron-phonon
      correlated states induced by two phase-locked optical pulses. Interferometric
      visibility showed that electronic coherence remained in a semiconducting GaAs
      crystal until ~40 fs; in contrast, electronic coherence disappeared within 10 fs
      in a semimetallic Bi crystal at room temperature, differing substantially from
      the long damping time of its phonon coherence, in the picosecond range.

PMID- 24662683
TI  - De novo Angiosarcoma of a Renal Allograft.
AB  - Prolonged exposure to immunosuppressive medication is a known risk factor for the
      development of post-transplant malignancies. De novo angiosarcoma in the post
      transplant population is extremely rare. We present an 81-year-old female who
      developed an angiosarcoma at the site of a functioning renal allograft and review
      contemporary treatment strategies for this devastating disease. The report
      underscores the importance of periodic surveillance for the development of
      malignancy in the immunosuppressed population. 

PMID- 24662684
TI  - Magnet(r) environments and the Affordable Care Act.

PMID- 24662685
TI  - It's all about flow in a complex adaptive system.
AB  - As systems evolve over time, their natural tendency is to become increasingly
      more complex. Studies in the field of complex systems have generated new
      perspectives on the application of management strategies in health systems. Much
      of this research appears as a natural extension of the cross-disciplinary field
      of systems theory. In this article, I discuss the Constructal Law and its impact
      on nurse workflow. 

PMID- 24662686
TI  - Designing tomorrow: changing our practice in response to evidence.

PMID- 24662687
TI  - The developmental levels in achieving Magnet(r) designation, part 2.
AB  - Magnet(r) designation has been shown to be a cost-effective strategy resulting in
      improved patient, staff, and organizational outcomes. Achieving this designation
      requires an organization to successfully progress through developmental levels on
      their journey. Part 1 of this article described a 4-level developmental model
      applied to each of the Magnet components. In part 2, we will discuss a 5-step
      process and leadership strategies for developing units or departments through the
      various levels. 

PMID- 24662688
TI  - Transformational leadership practices of nurse leaders in professional nursing
      associations.
AB  - OBJECTIVE: This study describes the transformational leadership (TL) practices of
      nurse leaders in professional nursing associations (PNAs). BACKGROUND:
      Professional nursing associations are vehicles to provide educational
      opportunities for nurses as well as leadership opportunities for members. Little
      has been published about the leadership practices of PNA members. METHOD: E-mail
      surveys of 448 nurse leaders in PNAs were conducted in 2013 using the Leadership
      Practices Inventory (LPI). RESULTS: The top 2 TL practices of these nurse leaders
      were enabling others to act and encouraging the heart. Respondents with more
      leadership training reported higher TL practices. CONCLUSION: This is the 1st
      study to describe TL practices of nurse leaders in PNAs. Results of this study
      show that nurse leaders of PNAs emulate practices of TL. Transformational leaders
      can mobilize and direct association members in reaching shared values,
      objectives, and outcomes. Understanding TL practices of nurse leaders in PNAs are
      important to the future of nursing in order to enable nurses to lead change and
      advance health through these organizations.

PMID- 24662689
TI  - Pod nursing on a medical/surgical unit: implementation and outcomes evaluation.
AB  - A medical/surgical unit at the University of Michigan Health System implemented a
      pod nursing model of care to improve efficiency and patient and staff
      satisfaction. One centralized station was replaced with 4 satellites and supplies
      were relocated next to patient rooms. Patients were assigned to 2 nurses who
      worked as partners. Three patient (satisfaction, call lights, and falls) and
      nurse (satisfaction and overtime) outcomes improved after implementation. Efforts
      should be focused on addressing patient acuity imbalances across assignments and
      strengthening communication among the healthcare team. Studies are needed to test
      the model in larger and more diverse settings. 

PMID- 24662691
TI  - Do staff nurse perceptions of nurse leadership behaviors influence staff nurse
      job satisfaction? The case of a hospital applying for Magnet(r) designation.
AB  - BACKGROUND: Nurse managers leadership behaviors influence the job satisfaction of
      staff nurses. Transformational leadership is 1 of the 5 components associated
      with the Magnet Recognition Program(r). OBJECTIVE: The aim of this study was to
      examine the relationship between staff nurse perception of nurse manager
      leadership behavior and staff nurse job satisfaction in a hospital on the
      Magnet(r) journey and the influence of nurse manager leadership style on staff
      nurse job satisfaction. METHODS: A descriptive, correlational design using a self
      report survey with convenience sampling was used for this quantitative research
      study. Staff nurses completed the Multifactor Leadership Questionnaire 5X Short
      Form, the Abridged Job Descriptive Index survey, and a demographic questionnaire.
      Pearson correlations and regression analyses were completed to explore the
      relationship and influence of nurse manager leadership style on staff nurse job
      satisfaction. RESULTS: Transformational and transactional leadership styles of
      nurse managers were positively related to staff nurse overall job satisfaction
      and satisfaction with opportunity for promotion. Passive-avoidant leadership
      style of nurse managers was negatively related to staff nurse satisfaction with
      work, promotion, supervision, and coworker. Satisfaction with nurse manager
      leadership was a positive influence on overall nurse job satisfaction when
      separately controlling for the influence of each leadership style. CONCLUSION:
      Transformational and transactional leadership styles should be taught and
      encouraged among nurse managers to positively influence the job satisfaction of
      staff nurses.

PMID- 24662690
TI  - An exploration of relational aggression in the nursing workplace.
AB  - OBJECTIVE: This study provides a 1st look at relational aggression (RA) and the
      consequences among nurses. BACKGROUND: Interpersonal hostility, bullying, and a
      toxic work environment (WE) can impact patient care delivery as well as nurses'
      personal health and job satisfaction. METHODS: The Relational Aggression
      Assessment Scale, measuring aggressors, victims, and bystanders, was used to
      measure RA in a sample of 842 nurses. Additional variables measured included a
      demographic profile, job satisfaction, and intent to leave. RESULTS: Nurses were
      most likely to identify with victim behaviors, but a minority of nurses reported
      relying on aggressor behaviors and bystander behaviors. There was a positive
      correlation among aggressor, victim, and bystander items, suggesting overlap in
      roles. CONCLUSIONS: A few relationally aggressive individuals can create a toxic
      WE. Interventions to address RA among nurses must be tested, as well as
      strategies for improving job satisfaction and promoting healthy WEs through
      positive relationships.

PMID- 24662692
TI  - Structural empowerment of clinical nurse managers.
AB  - OBJECTIVE: The purpose of this study was to describe perceptions of structural
      empowerment of clinical nurse managers (CNMs) in 1 large healthcare system.
      BACKGROUND: The recruitment and retention of CNMs are crucial to the future of
      healthcare institutions. Understanding the extent to which CNMs feel supported in
      the work environment and have access to resources, information, support, and
      opportunities to learn and develop will be beneficial to organizational
      effectiveness. METHODS: The sample included 140 CNMs from 1 large healthcare
      system in the northeastern United States. RESULTS: Consistent with previous
      research, CNMs in the present study had moderate levels of empowerment. They had
      lower than expected subscale scores on the resources subscale and acceptable
      scores on the subscales of support, formal power, and informal power.
      CONCLUSIONS: In the current changing healthcare environment, it is important to
      gain more understanding of the role of CNMs who are crucial to quality care and
      patient and nurse satisfaction. This study provides important baseline
      information about perceptions of structural empowerment among CNMs. Interventions
      that can be initiated to enhance the CNM empowerment are presented.

PMID- 24662693
TI  - BSN completion barriers, challenges, incentives, and strategies.
AB  - OBJECTIVE: The objectives of this study were to explore RN perceptions regarding
      barriers/challenges and incentives/supports for BSN completion and identify
      recommendations to increase RN BSN completion. BACKGROUND: The Institute of
      Medicine's 2011 The Future of Nursing report recommended the proportion of RNs
      with a BSN increase to 80% by 2020. METHOD: This qualitative study included 41
      RNs who participated in 1 of 6 focus groups based on their BSN completion status.
      RESULTS: Primary themes were sacrifices, barriers/challenges,
      incentives/supports, value, how to begin, and pressure. Primary BSN completion
      barriers/challenges were work-life balance and economic issues.
      Incentives/supports identified were financial compensation, assistance from
      employer and academic institution, and encouragement from family. Institutional
      strategies recommended for increasing BSN completion rates were improved access
      to education and financial support facilitated by collaboration between hospitals
      and academic institutions. CONCLUSIONS: Exploring RN barriers/challenges and
      incentives/supports for BSN completion can lead to implementation of
      institutional strategies, such as tuition reimbursement and academic
      collaboration.

PMID- 24662694
TI  - Safety watch: reducing constant observation through nurse empowerment and
      accountability.
AB  - Safety watch (SW), a nurse-driven surveillance program, provides a framework for
      the appropriate level of patient observation. It empowers nurses to initiate
      flexible levels of patient safety observation that can be adjusted based on the
      patient's need and be discontinued safely at the earliest opportunity. The SW
      program resulted in dramatic reductions in constant observation and restraint use
      while sustaining quality of care. 

PMID- 24662695
TI  - Adjustment of directly measured adipose tissue volume in infants.
AB  - BACKGROUND: Direct measurement of adipose tissue (AT) using magnetic resonance
      imaging is increasingly used to characterise infant body composition. Optimal
      techniques for adjusting direct measures of infant AT remain to be determined.
      OBJECTIVES: To explore the relationships between body size and direct measures of
      total and regional AT, the relationship between AT depots representing the
      metabolic load of adiposity and to determine optimal methods of adjusting
      adiposity in early life. DESIGN: Analysis of regional AT volume (ATV) measured
      using magnetic resonance imaging in longitudinal and cross-sectional studies.
      SUBJECTS: Healthy term infants; 244 in the first month (1-31 days), 72 in early
      infancy (42-91 days). METHODS: The statistical validity of commonly used indices
      adjusting adiposity for body size was examined. Valid indices, defined as
      mathematical independence of the index from its denominator, to adjust ATV for
      body size and metabolic load of adiposity were determined using log-log
      regression analysis. RESULTS: Indices commonly used to adjust ATV are
      significantly correlated with body size. Most regional AT depots are optimally
      adjusted using the index ATV/(height)(3) in the first month and ATV/(height)(2)
      in early infancy. Using these indices, height accounts for<2% of the variation in
      the index for almost all AT depots. Internal abdominal (IA) ATV was optimally
      adjusted for subcutaneous abdominal (SCA) ATV by calculating IA/SCA(0.6).
      CONCLUSIONS: Statistically optimal indices for adjusting directly measured ATV
      for body size are ATV/height(3) in the neonatal period and ATV/height(2) in early
      infancy. The ratio IA/SCA ATV remains significantly correlated with SCA in both
      the neonatal period and early infancy; the index IA/SCA(0.6) is statistically
      optimal at both of these ages.

PMID- 24662697
TI  - The effect of holiday weight gain on body weight.
AB  - The topic of holiday weight gain has been a frequent subject of the lay media;
      however, scientific interest has only been recent. Multiple studies in Western
      societies have reported average weight gains among adults during the period
      between mid-November and mid-January that were about 0.5 kg. The range in
      individual weight changes was large, however, and the already overweight and
      obese gain more weight than those who are healthy weight. When the average gain
      across the year was also measured, the holiday weight was the major contributor
      to annual excess weight gain. Efforts patterned to increase awareness to energy
      balance and body weight have been shown to be successful at reducing such gain.
      An exception to holiday weight gain being a major contributor to annual excess
      gain has been children, in whom summer weight gains have been observed to be the
      major contributor to average excess weight gain.

PMID- 24662698
TI  - Persisting adiposity following chronic consumption of 10% sucrose solution:
      strain differences and behavioural effects.
AB  - The metabolic consequences of providing rats with extended access to sugar
      solutions have varied across studies. The two experiments in this study examined
      the effects of 8 weeks of 24-h access to 10% sucrose solution on adult Wistar
      rats. This was followed by 6 weeks of food restriction with no access to sucrose
      during which the behavioural effects of prior sucrose consumption on reward
      oriented behaviour (Experiment 1) and reversal learning (Experiment 2) were
      assessed. In a comparison between rat strains, Experiment 1 found that sucrose
      accelerated weight gain in Albino but not Hooded Wistar rats, while sucrose-fed
      rats of both strains exhibited elevated fasting blood glucose and resistance to
      insulin. Importantly, at cull retroperitoneal fat deposits were elevated in
      sucrose-fed rats, at which point glucose and insulin had resolved to control
      levels and liver triglyceride content did not differ between groups. Experiment 2
      also found that retroperitoneal fat content was higher in sucrose-fed rats at
      cull, after 6 weeks of behavioural testing without sucrose and with restricted
      access to food, and found a similar effect for epididymal fat. Behavioural
      testing in Experiment 1 found that sucrose exposure had no effect on habit
      formation assessed using an outcome devaluation paradigm. However, instrumental
      responding by sucrose-fed Albino rats was the least affected by pre-feeding,
      indicating a relationship between sucrose-induced obesity and food-seeking
      behaviour. In Experiment 2, sucrose-fed and control rats did not differ on a
      discrimination reversal task. In conclusion, this study demonstrates that the
      behavioural and metabolic effects of sucrose consumption vary with strain.
      Further, results indicate that sucrose consumption can lead to lasting increases
      in adipose tissue stores, a finding which has significant implications for human
      diets.

PMID- 24662699
TI  - Psychobiological examination of liking and wanting for fat and sweet taste in
      trait binge eating females.
AB  - The hedonic value of food has been conceptualised as a combination of how much a
      food is liked and how much a food is wanted in a given moment. These
      psychobiological constructs help to explain choices about which foods to eat and
      have a primary role in how much energy is consumed. Moreover the processes of
      liking and wanting for food are not always equivalent and may differ by degree
      according to the food in question, state of satiety, body composition and
      individual differences in dispositional eating behaviour traits. Here we report
      progress on the behavioural quantification of food hedonics in the laboratory
      setting through assessment of 'explicit liking' and 'implicit wanting' according
      to perceived fat content and/or sweet taste of common foods. We review recent
      experimental evidence examining the role of liking and wanting as features of
      'trait binge eating' (assessed using the Binge Eating Scale)-a non-clinical
      psychometric marker for susceptibility to overeating and increased risk of weight
      gain. Our data show that trait binge eating can be viewed as an ecologically
      valid, behavioural phenotype of obesity, characterised by reliable psychological
      and anthropometric characteristics. Enhanced implicit wanting for sweet foods
      with high fat content is a psychobiological feature of susceptibility to
      overeating and offers a potential target for improving appetite control. 

PMID- 24662700
TI  - Changes in meningococcal C epidemiology and vaccine effectiveness after vaccine
      introduction and schedule modification.
AB  - PURPOSE: Meningococcal C conjugate vaccine was included in December 2000 in the
      Spanish childhood vaccination at 2, 4 and 6 months of age. In 2006, routine
      vaccination was modified to two doses at 2 and 4-6 months and a booster dose
      during the second year of age. Additionally, successive catch-up campaigns were
      launched to extend protection to older groups. This study provides long-term
      information about the vaccine effectiveness (VE) and the impact of vaccination in
      meningococcal C disease epidemiology in Spain. METHODS: We assessed surveillance
      data from season 1996/97 to season 2012/13 to describe changes in incidence and
      lethality of the disease. The vaccine-effectiveness study covered all cases
      notified from January 1st of 2001 onwards and evaluated vaccine effectiveness in
      both routines and in catch-up campaigns. To investigate the decline in protection
      over time, we compared the vaccine effectiveness within 1 year and more than one
      year since vaccination. RESULTS: The incidence of meningococcal serogroup C
      disease decreased first in those age-groups targeted for vaccination. But after
      2006/07 season the decrease in incidence was generalised. Vaccine effectiveness
      was high in all vaccination programmes, although 2, 4-6 months (+ booster dose)
      routine showed higher overall vaccine effectiveness than 2, 4 and 6 months
      routine (99.3% vs. 90.2%). VE >1 year since vaccination was lower in 2, 4 and 6
      months compared to 2 and 4-6 months (+ booster) routine (81.4% vs. 89.1%). For
      catch-up campaigns, VE increased and loss of VE decreased with the age of
      administration. Overall VE was 94.83 (CI95%: 93.37, 95.97), 98.82 (CI95%: 97.96,
      99.31) and 90.89 (CI95%: 87.79, 93.21) for <= 1 and >1 year since vaccination,
      respectively. CONCLUSIONS: The meningococcal C conjugate vaccination programme
      has been extremely successful in controlling the disease and continues to be
      evaluated and adapted to the changes in the epidemiology of the disease to ensure
      long-term vaccine protection.

PMID- 24662701
TI  - Development of a recombinant toxin fragment vaccine for Clostridium difficile
      infection.
AB  - Clostridium difficile infection (CDI) is the major cause of antibiotic-associated
      diarrhea and pseudomembranous colitis, a disease associated with significant
      morbidity and mortality. The disease is mostly of nosocomial origin, with elderly
      patients undergoing anti-microbial therapy being particularly at risk. C.
      difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two
      toxins act synergistically to damage and impair the colonic epithelium, and are
      primarily responsible for the pathogenesis associated with CDI. The feasibility
      of toxin-based vaccination against C. difficile is being vigorously investigated.
      A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was
      reported to be safe and immunogenic in healthy volunteers and is now undergoing
      evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects,
      a chemical inactivation step must be included in the manufacturing process of
      this toxin-based vaccine. In addition, the large-scale production of highly toxic
      antigens could be a challenging and costly process. Vaccines based on non-toxic
      fragments of genetically engineered versions of the toxins alleviate most of
      these limitations. We have evaluated a vaccine assembled from two recombinant
      fragments of TcdB and explored their potential as components of a novel
      experimental vaccine against CDI. Golden Syrian hamsters vaccinated with
      recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed
      high titer IgG responses and potent neutralizing antibody titers. We also show
      here that the recombinant vaccine protected animals against lethal challenge with
      C. difficile spores, with efficacy equivalent to the toxoid vaccine. The
      development of a two-segment recombinant vaccine could provide several advantages
      over toxoid TcdA/TcdB such as improvements in manufacturability. 

PMID- 24662703
TI  - Use of adenovirus as a model system to illustrate a simple method using standard
      equipment and inexpensive excipients to remove live virus dependence on the cold
      chain.
AB  - Thermolability of complex biological molecules is a major consideration for the
      long-term maintenance of titer during periods of storage. The development of a
      simple, cost effective method for long term storage of virus samples, which
      maintains viral titer would prove useful for a wide variety of applications
      including the preservation of viral vaccines, and is paramount for alleviating
      the reliance upon the cold chain. We have investigated the potential use of a
      method adapted for this purpose originating from a natural mechanism used by
      plants which helps to maintain the integrity of seeds, enabling them to overcome
      extensive periods of temperature elevation and desiccation. As maturation of a
      seed progresses, many complex biological macromolecules are laid down which
      maintain the germination potential. Sucrose and raffinose (in addition to other
      oligosaccharides) are commonly found to accumulate. In addition highly charged
      protein molecules accumulate, Late Embryogenesis Abundant (LEA) proteins,
      reaching their maximal level when the seed is most desiccation and thermally
      tolerant, and indeed are among the first molecules to be lost when germination is
      initiated. We have examined the potential use of sucrose and raffinose in concert
      with chemical replacements for the LEA, which when dried with the active product
      forms an amorphous solid able to maintain the titer of infectious Adenovirus at
      elevated temperatures for extended periods, in the case of lyophilized
      presentations several months at 37  degrees C, or as liquid, stability for
      several weeks at 37  degrees C was achieved. We demonstrate that after embedding
      the active product in the matrix, the viral titer is preserved even at
      temperatures for relatively extended periods at temperatures significantly
      greater than ambient. In addition we believe that these results could open the
      way for a new type of vaccine which we refer to as a hybrid stability vaccine,
      whereby for the first time the same excipient components are used to confer
      stability in both liquid and solid forms (albeit at different concentrations)
      which may ultimately result in a stable vaccine which has a very high stability
      index whilst dry, whereas upon reconstitution using nothing more than WFI at
      proscribed volumes, the vaccine would benefit from having much improved stability
      during the administration procedures. This paper describes the use of Adenovirus
      (itself fast becoming a vector of choice for a new generation of vaccines) as a
      model system, and identifies non-toxic, inexpensive excipients which are
      compatible with current manufacturing processes which could be instrumental in
      removing the dependence upon the cold chain.

PMID- 24662702
TI  - A multi-stage malaria vaccine candidate targeting both transmission and asexual
      parasite life-cycle stages.
AB  - Effective control and eventual eradication of malaria drives the imperative need
      for clinical development of a malaria vaccine. Asexual parasite forms are
      responsible for clinical disease and death while apathogenic gametocytes are
      responsible for transmission from man to mosquito. Vaccines that combine antigens
      from both stages may provide direct protection and indirect benefit by reducing
      the force of infection. We constructed a chimeric antigen composed of a fragment
      of the Plasmodium falciparum (Pf) glutamate-rich protein fused in frame to a
      correctly folded fragment of Pfs48/45. The chimera was produced in Lactococcus
      lactis and induced robust antibody responses in rodents to the individual
      components. Specific antibodies showed strong transmission blocking activity
      against multiple Pf-strains in the standard membrane feeding assay and functional
      activity against asexual stages in the antibody dependent cellular inhibition
      assay. The combined data provide a strong rationale for entering the next phase
      of clinical grade production and testing.

PMID- 24662696
TI  - An evolving scientific basis for the prevention and treatment of pediatric
      obesity.
AB  - The 2013 Pennington Biomedical Research Center's Scientific Symposium focused on
      the treatment and management of pediatric obesity and was designed to (i) review
      recent scientific advances in the prevention, clinical treatment and management
      of pediatric obesity, (ii) integrate the latest published and unpublished
      findings and (iii) explore how these advances can be integrated into clinical and
      public health approaches. The symposium provided an overview of important new
      advances in the field, which led to several recommendations for incorporating the
      scientific evidence into practice. The science presented covered a range of
      topics related to pediatric obesity, including the role of genetic differences,
      epigenetic events influenced by in utero development, pre-pregnancy maternal
      obesity status, maternal nutrition and maternal weight gain on developmental
      programming of adiposity in offspring. Finally, the relative merits of a range of
      various behavioral approaches targeted at pediatric obesity were covered,
      together with the specific roles of pharmacotherapy and bariatric surgery in
      pediatric populations. In summary, pediatric obesity is a very challenging
      problem that is unprecedented in evolutionary terms; one which has the capacity
      to negate many of the health benefits that have contributed to the increased
      longevity observed in the developed world. 

PMID- 24662704
TI  - An inactivated oil-emulsion fowl Adenovirus serotype 4 vaccine provides broad
      cross-protection against various serotypes of fowl Adenovirus.
AB  - The number of clinical cases of inclusion body hepatitis (IBH) and
      hydropericardium-hepatitis syndrome (HHS) has been increasing, resulting in
      considerable economic losses in many countries. Currently, only fowl Adenovirus
      (FAdV) serotype 4 (FAdV-4) has been reported as the causative agent of HHS,
      whereas IBH can be caused by all 12 serotypes of FAdV. For protection against
      HHS, various live and killed FAdV serotype 4 vaccines have been developed.
      However, there is a concern whether these vaccines composed of FAdV-4 alone could
      provide protection against IBH, which is caused by other serotypes of virulent
      FAdVs. To date, there have been no reports evaluating the protective efficacy of
      the FAdV-4 vaccine against other serotypes of FAdV. Thus, we investigated the
      cross-protection efficacy of an inactivated oil-emulsion FAdV-4 vaccine against
      various serotypes of FAdV field isolates. Our study demonstrated that the
      inactivated oil-emulsion FAdV-4 vaccine could provide broad cross-protection
      against various serotypes of FAdV in not only vaccinated birds, but also the
      progenies of vaccinated breeder. Therefore, we conclude that the inactivated oil
      emulsion FAdV-4 vaccine could be effective in preventing the spread of various
      other serotypes of FAdV as well as FAdV-4 infection in the poultry industry. 

PMID- 24662706
TI  - Exploring mucosal immunization with a recombinant influenza virus carrying an HIV
      polyepitope in mice with pre-existing immunity to influenza.
AB  - HIV-1 vaccines based on recombinant vectors have been developed to elicit immune
      responses; however, the failure of the STEP HIV-1 vaccine trial has caused
      concern regarding the impact on vaccine efficacy of pre-existing vector
      seropositivity in humans. By using a mouse model of infection, we evaluated the
      immune responses elicited by intranasal and vaginal immunization with the
      recombinant influenza virus WSN/CKG carrying the PCLUS3-P18 peptide and a Gag
      epitope in its hemagglutinin, and the impact of pre-existing vector immunity on
      protection against recombinant vaccinia virus challenge. We found that despite
      the protective immunity induced in naive mice by the WSN/CKG virus via either
      route, the vaginal immunization of mice with pre-existing influenza immunity
      restricted vPE16 replication more significantly in the ovaries than intranasal
      immunization. Thus, successful vaccination strategies under limiting conditions,
      such as pre-existing vector immunity, require the local induction of mucosal
      immunity at the site of virus infection. 

PMID- 24662705
TI  - Efficacy of an inactivated FeLV vaccine compared to a recombinant FeLV vaccine in
      minimum age cats following virulent FeLV challenge.
AB  - The aim of the study was to determine the efficacy of an inactivated feline
      leukemia virus (FeLV) vaccine (Versifel((r)) FeLV, Zoetis.) compared to a
      recombinant FeLV vaccine (Purevax((r)) FeLV, Merial Animal Health) in young cats,
      exposed under laboratory conditions to a highly virulent challenge model. The
      study was designed to be consistent with the general immunogenicity requirements
      of the European Pharmacopoeia 6.0 Monograph 01/2008:1321-Feline Leukaemia Vaccine
      (Inactivated) with the exception that commercial-strength vaccines were assessed.
      Fifty seronegative cats (8-9 weeks old) were vaccinated subcutaneously on two
      occasions, three weeks apart, with either placebo (treatment group T01), Versifel
      FeLV Vaccine (treatment group T02), or Purevax FeLV Vaccine (treatment group T03)
      according to the manufacturer's directions. Cats were challenged three weeks
      after the second vaccination with a virulent FeLV isolate (61E strain).
      Persistent FeLV antigenemia was determined from 3 to 15 weeks postchallenge. Bone
      marrow samples were tested for the presence of FeLV proviral DNA to determine
      FeLV latent infection. At week 15 after challenge with the virulent FeLV 61E
      strain, the Versifel FeLV Vaccine conferred 89.5% protection against FeLV
      persistent antigenemia and 94.7% protection against FeLV proviral DNA integration
      in bone marrow cells. In comparison, the Purevax FeLV Vaccine conferred 20%
      protection against FeLV persistent antigenemia and 35% protection against FeLV
      proviral DNA integration in bone marrow cells following challenge. The data from
      this study show that the Versifel FeLV Vaccine was efficacious in preventing both
      FeLV persistent p27 antigenemia and FeLV proviral DNA integration in bone marrow
      cells of cats challenged with this particular challenge model under laboratory
      conditions and provided better protection than Purevax FeLV in this experimental
      challenge model with highly virulent FeLV. 

PMID- 24662707
TI  - The adjuvant PCEP induces recruitment of myeloid and lymphoid cells at the
      injection site and draining lymph node.
AB  - Poly[di(sodiumcarboxylatoethylphenoxy)phosphazene] (PCEP) has shown great
      potential as a vaccine adjuvant, but the mechanisms that mediate its adjuvant
      activity have not been investigated. Previously, we had reported the potential of
      PCEP to induce cytokines and chemokines at the site of injection. Hence, we
      hypothesized that PCEP creates strong immuno-competent environment leading to
      recruitment of immune cells at the injection site. Intramuscular injection of
      mice with PCEP induced significant recruitment of neutrophils, macrophages,
      monocytes, dendritic cells (DCs), and lymphocytes at the site of injection as
      well as in the draining lymph nodes. Flow cytometric analysis showed that the
      majority of the recruited immune cells took up and/or were associated with PCEP
      at the injection site, with lymphocytes taking up PCEP in lesser quantity.
      Further, confocal analysis revealed intracytoplasmic lysosomal localization of
      PCEP in recruited immune cells. These observations suggest that recruitment of
      distinct immune cells to the site of injection site may be an important mechanism
      by which PCEP potentiates immune responses to antigens.

PMID- 24662708
TI  - Acceptability of a hypothetical group B strep vaccine among pregnant and recently
      delivered women.
AB  - OBJECTIVE: Group B Streptococcus (GBS) causes significant infant morbidity and
      mortality. Promising GBS vaccines are currently in clinical trials. Because GBS
      vaccines would be the first to specifically target pregnant women, we sought to
      assess acceptability of a hypothetical GBS vaccine. STUDY DESIGN: We performed an
      internet survey among currently pregnant or recently delivered women receiving
      care at one of 9Ob/Gyn practices in Colorado. Vaccine acceptability was assessed
      using questions based on constructs from the Health Belief Model. Multivariable
      analyses assessed the characteristics associated with GBS vaccine acceptability
      during the current/recent pregnancy. RESULTS: The response rate was 50% (n=231).
      While 78% agreed that a GBS vaccine would be a good way to protect newborns, 90%
      and 83% agreed, respectively, that they worried generally about the safety and
      effectiveness of new vaccines. Moreover, 39% believed it is generally dangerous
      for pregnant women to get vaccines. Seventy nine percent 'definitely' or
      'probably' would have gotten a GBS vaccine in their most recent pregnancy if
      available. The most influential factors associated with this outcome were a
      strong belief in the vaccine's benefits (adjusted odds ratio [AOR] 6.37, 95%
      confidence interval [CI] 2.01-20.16), and low perceived barriers to vaccination
      (AOR 0.11, 95% CI (0.03-0.37)). CONCLUSION: A GBS vaccine may be acceptable to
      pregnant women but would benefit from strong provider support and education about
      the risks and consequences of GBS infection and the benefits to vaccination.

PMID- 24662709
TI  - Vaccines for Acinetobacter baumannii: thinking "out of the box".

PMID- 24662710
TI  - Cost-effectiveness and equity impacts of three HPV vaccination programmes for
      school-aged girls in New Zealand.
AB  - BACKGROUND: As with many high-income countries, vaccination coverage against
      human papilloma virus (HPV) infection is not high in New Zealand (NZ) at 47% in
      school-aged girls for three doses. We estimate the health gains, net-cost and
      cost-effectiveness of the currently implemented HPV national vaccination
      programme of vaccination dispersed across schools and primary care, and two
      alternatives: school-based only (assumed coverage as per Australia: 73%), and
      mandatory school-based vaccination but with opt-out permitted (coverage 93%). We
      also generate estimates by social group (sex, ethnic and deprivation group).
      METHODS: A Markov macro-simulation model was developed for 12-year-old girls and
      boys in 2011, with future health states of: cervical cancer, pre-cancer (CIN I
      III), genital warts, and three other HPV-related cancers (oropharyngeal, anal,
      vulvar cancer). In each state health sector costs, including additional health
      sector costs from extra life, and quality-adjusted life years (QALYs) were
      accumulated. RESULTS: The current HPV vaccination programme has an estimated cost
      effectiveness of NZ$18,800/QALY gained (about US$9700/QALY gained using the
      OECD's purchasing power parities; 95% UI: US$6900 to $33,700) compared to the
      status quo in NZ prior to 2008 (no vaccination, screening alone). The incremental
      cost-effectiveness ratio (ICER) of an intensive school-based only programme of
      girls, compared to the current situation, was US$33,000/QALY gained. Mandatory
      vaccination appeared least cost-effective (ICER compared to school-based of
      US$117,000/QALY gained, but with wide 95% uncertainty limits from $56,000 to
      $220,000). All interventions generated more QALYs per 12-year-old for Maori
      (indigenous population) and people living in deprived areas (range 5-25% greater
      QALYs gained). INTERPRETATION: A more intensive school-only vaccination programme
      seems warranted. Reductions in vaccine price will greatly improve cost
      effectiveness of all options, possibly making a law for mandatory vaccination
      optimal from a health sector perspective. All interventions could reduce ethnic
      and socioeconomic disparities in HPV-related disease.

PMID- 24662711
TI  - Bacteria expressed hepatitis E virus capsid proteins maintain virion-like
      epitopes.
AB  - The protein encoded by ORF2 in hepatitis E virus (HEV) is the only capsid protein
      for this single-stranded RNA virus. It was previously shown that 148 aa (aa 459
      606) was needed for dimer formation, whereas 239 aa (aa 368-606) was necessary to
      form virus-like particles (VLPs). The self-assembled VLPs of p239 were
      characterized with a series of methods including high performance size-exclusion
      chromatography to demonstrate the particulate nature of purified and properly
      refolded p239. A neutralizing and protective mouse monoclonal antibody (mAb) 8C11
      was previously shown to bind three discontinuous peptide segments in the dimer.
      In addition to the good binding activity to recombinant dimeric form, E2s or E2,
      and VLP form p239, we demonstrated that 8C11 was able to capture the authentic
      HEV virions. The capability of virus capturing was demonstrated with a titration
      curve from 10(5) to 10(7) HEV genome copies, making binding activity to 8C11 a
      surrogate marker of virion-like epitopes on recombinant VLPs as well as vaccine
      efficacy in eliciting protective and neutralizing antibodies. Taken together, it
      was demonstrated that Escherichia coli expressed pORF2 proteins, p239 in
      particular, maintain the virion-like epitopes on VLP surface. This is consistent
      with the fact that p239 was demonstrated to be an effective prophylactic vaccine
      (recently licensed as Hecolin((r)) in China) against HEV-induced hepatitis in a
      large scale clinical trial. 

PMID- 24662712
TI  - A three component mix of thioredoxin-L2 antigens elicits broadly neutralizing
      responses against oncogenic human papillomaviruses.
AB  - Current human papillomavirus (HPV) vaccines based on major capsid protein L1
      virus-like particles (VLP) provide potent type-specific protection against
      vaccine-type viruses (mainly HPV16 and 18), but cross-protect against only a
      small subset of the approximately 15 oncogenic HPV types. It is estimated that L1
      VLP vaccines, which require a fairly complex production system and are still
      quite costly, fail to cover 20-30% of HPV cervical cancers worldwide, especially
      in low-resource countries. Alternative antigens relying on the N-terminal region
      of minor capsid protein L2 are intrinsically less immunogenic but capable of
      eliciting broadly neutralizing responses. We previously demonstrated the enhanced
      immunogenicity and cross-neutralization potential of an easily produced
      recombinant L2 antigen bearing the HPV16 L2(20-38) peptide epitope internally
      fused to bacterial thioredoxin (Trx). However, antibodies induced by Trx-HPV16
      L2(20-38) failed to cross-neutralize notable high-risk HPV types such as HPV31.
      In the present work, the Trx-L2 design was modified to include L2 sequence
      information from the highly divergent HPV31 and HPV51 types in addition to HPV16,
      with the aim of extending cross-neutralization. Multivalent antigens comprising
      L2(20-38) peptides from all three HPV types on a single Trx scaffold molecule
      were compared to a mixture of the three type-specific monovalent Trx-L2 antigens.
      While multivalent antigens as well as the mixed antigens elicited similar anti
      HPV16 neutralization titers, cross-reactive responses against HPV31 and HPV51
      were of higher magnitude and more robust for the latter formulation. A mixture of
      monovalent Trx-L2 antigens thus represents a candidate lead for the development
      of a broadly cross-protective, low-cost second-generation anti-HPV vaccine. 

PMID- 24662713
TI  - Relationship between 25-hydroxyvitamin D and newly diagnosed type 2 diabetes
      mellitus in postmenopausal women with osteoporosis.
AB  - OBJECTIVE: The aim of the study was to determine a correlation between the level
      of 25-hydroxivitamin D (25-OHD) and the incidence of diabetes. SUBJECTS AND
      METHODS: In this prospective observational study, 97 (out of an initial 100)
      Caucasian women with osteoporosis (OS) were monitored for 2 years for the
      incidence of diabetes. Logistic regression analysis was used to establish an
      association with and prognostic value of vitamin D for the onset of type 2
      diabetes mellitus, as well as insulin resistance, body mass index (BMI), total
      cholesterol and triglyceride levels in the development of diabetes. The serum
      level of 25-OHD was measured using immunochemiluminescence in March and April
      2011. RESULTS: Of the 97 patients (mean age 51.64 +/- 5.86 years, range 36.0
      73.0), 21 (21.65%) were diagnosed with diabetes during the observational period.
      The study showed that the 22 patients with low levels of vitamin D were more
      susceptible to diabetes (odds ratio = 0.958). The cut-off value of vitamin D
      using a receiver operating characteristic curve was 62.36 nmol/l with a
      sensitivity of 39.5% and a specificity of 90.5%. With an increase in BMI and
      triglyceride levels, women were, respectively, 1,591 and 2,821 times more likely
      to get diabetes than those without an increase. CONCLUSION: This study showed
      that the patients with postmenopausal OS and hypovitaminosis D, besides a high
      BMI, elevated triglyceride levels and insulin resistance, had an increased risk
      of developing type 2 diabetes.

PMID- 24662716
TI  - Early and total neonatal mortality in relation to birth setting in the United
      States, 2006-2009.
AB  - OBJECTIVE: We examined neonatal mortality in relation to birth settings and birth
      attendants in the United States from 2006 through 2009. STUDY DESIGN: Data from
      the Centers for Disease Control and Prevention-linked birth and infant death
      dataset in the United States from 2006 through 2009 were used to assess early and
      total neonatal mortality for singleton, vertex, and term births without
      congenital malformations delivered by midwives and physicians in the hospital and
      midwives and others out of the hospital. Deliveries by hospital midwives served
      as the reference. RESULTS: Midwife home births had a significantly higher total
      neonatal mortality risk than deliveries by hospital midwives (1.26 per 1000
      births; relative risk [RR], 3.87 vs 0.32 per 1000; P < .001). Midwife home births
      of 41 weeks or longer (1.84 per 1000; RR, 6.76 vs 0.27 per 1000; P < .001) and
      midwife home births of women with a first birth (2.19 per 1000; RR, 6.74 vs 0.33
      per 1000; P < .001) had significantly higher risks of total neonatal mortality
      than deliveries by hospital midwives. In midwife home births, neonatal mortality
      for first births was twice that of subsequent births (2.19 vs 0.96 per 1000; P <
      .001). Similar results were observed for early neonatal mortality. The excess
      total neonatal mortality for midwife home births compared with midwife hospital
      births was 9.32 per 10,000 births, and the excess early neonatal mortality was
      7.89 per 10,000 births. CONCLUSION: Our study shows a significantly increased
      total and early neonatal mortality for home births and even higher risks for
      women of 41 weeks or longer and women having a first birth. These significantly
      increased risks of neonatal mortality in home births must be disclosed by all
      obstetric practitioners to all pregnant women who express an interest in such
      births.

PMID- 24662717
TI  - Utility of a comparability score for reporting studies using whole population
      data. Reply.

PMID- 24662719
TI  - Utility of a comparability score for reporting studies using whole population
      data.

PMID- 24662718
TI  - The effects of reproductive hormones on the physical properties of cervicovaginal
      fluid.
AB  - OBJECTIVE: The purpose of this study was to determine the impact of
      contraception, menopause, and vaginal flora on the physical and biochemical
      properties of cervicovaginal fluid (CVF). STUDY DESIGN: Vaginal swabs, CVF, and
      cervicovaginal lavage (CVL) were collected from a total of 165 healthy
      asymptomatic women including: postmenopausal women (n = 29), women in the
      proliferative (n = 26) or follicular (n = 27) phase, and women using the
      levonogestrel intrauterine device (n = 28), depomedroxyprogesterone acetate (n =
      28) or combined oral contraceptives (n = 27). Vaginal smears were evaluated using
      the Nugent score. The osmolality, viscosity, density, and pH of CVL samples were
      measured. RESULTS: CVL from postmenopausal women and women with abnormal vaginal
      flora was less viscous and had higher pH than premenopausal women and women with
      normal flora, respectively. Women using hormonal contraceptives had more viscous
      CVL as compared with premenopausal women not using hormonal contraceptives, but
      this increase in viscosity was mitigated in the presence of bacterial vaginosis.
      Women using depomedroxyprogesterone acetate had less total protein in the CVL as
      compared with women using the levonogestrel intrauterine device, and had similar
      protein content when compared with postmenopausal women. CONCLUSION: The
      differences in CVL protein content between depomedroxyprogesterone acetate and
      levonogestrel intrauterine device suggest that type of progesterone and route of
      delivery impact the vaginal environment. Contraceptive hormone users had more
      viscous CVL than women not using contraceptives. However, the presence of
      bacterial vaginosis impacted both the pH and viscosity (regardless of hormonal
      contraceptive use), demonstrating that vaginal flora has a greater impact on the
      physical properties of CVF than reproductive hormones.

PMID- 24662720
TI  - Molecular structure, vibrational spectroscopic, hyperpolarizability, natural bond
      orbital analysis, frontier molecular orbital analysis and thermodynamic
      properties of 2,3,4,5,6-pentafluorophenylacetic acid.
AB  - The FT-IR (4000-400cm(-)(1)) and FT-Raman spectra (3500-100cm(-)(1)) of 2,3,4,5,6
      pentafluorophenylacetic acid (PAA) have been recorded. Density functional theory
      calculation with LSDA/6-31+G(d,p) and B3LYP/6-31+G(d,p) basis sets have been used
      to determine ground state molecular geometries (bond lengths and bond angles),
      harmonic vibrational frequencies, infrared intensities, Raman intensities and
      bonding features of the title compound. The assignments of the vibrational
      spectra have been carried out with the help of normal coordinate analysis (NCA)
      following the scaled quantum mechanical force field (SQMFF) methodology. The
      first order hyperpolarizability (beta0) and related properties (beta, alpha0 and
      Deltaalpha) of PAA are calculated using B3LYP/6-31+G(d,p) method on the finite
      field approach. The calculated first hyperpolarizability shows that the molecule
      is an attractive molecule for future applications in non-linear optics. The
      stability of molecule has been analyzed by using NBO analysis. The calculated
      HOMO and LUMO energies show that charge transfer occurs within this molecule.
      Mulliken population analysis on atomic charges is also calculated. Thermodynamic
      properties (heat capacity, enthalpy, Gibb's free energy and entropy) of the title
      compound at different temperatures were calculated. 

PMID- 24662721
TI  - Diffused reflectance and structure analysis for the nano-matrix (ZnO(1-x)SiO2(x))
      system.
AB  - Optical and structural properties of the investigated matrix ZnO(1-x)SiO2(x)
      system were characterized by various techniques such as X-ray analysis and UV-VIS
      NIR absorption. The structural changes of the studied nano-matrix ZnO(1-x)SiO2(x)
      with the concentration of nanosilica are checked by X-ray analysis measurement.
      The crystal structures for ZnO, (ZnO)0.75(SiO2)0.25, (ZnO)0.50(SiO2)0.50 and
      (ZnO)0.25(SiO2)0.75 and pure SiO2 are hexagonal, monoclinic, tetragonal,
      orthorhombic and amorphous respectively and detailed crystal parameters are
      obtained. The electronic properties of ZnO(1-x)SiO2(x) are investigated, where
      the optical band gaps for the five studied systems are 3.22eV, 3.24eV, 3.27eV,
      3.30eV and 4.5eV respectively. It is clear that the band gap increases with
      increasing SiO2 content. Mixing the ZnO with SiO2 enhance the UV response of
      these materials which is confirmed by diffused reflectance spectrum used to
      analyze the UV response of the studied systems. 

PMID- 24662722
TI  - Drugs for peptic ulcer disease GERD.

PMID- 24662723
TI  - Effectiveness of music intervention in ameliorating cancer patients' anxiety,
      depression, pain, and fatigue: a meta-analysis.
AB  - BACKGROUND: This is the first study to use meta-analysis as a scientific
      technique to provide an integrated analysis of the effectiveness of music
      intervention in cancer patients. OBJECTIVES: The purpose of this study was, using
      the meta-analysis method, to present a summary of existing research and explore
      the effectiveness of music intervention in ameliorating anxiety, depression,
      pain, and fatigue in cancer patients. METHODS: The present study collected
      quantitative study designs sought of music intervention for cancer patients
      published from 2002 to 2012. These studies were then cross-referenced using
      Medical Subject Headings for topics on music intervention and cancer patients.
      Outcome indicators were anxiety, depression, pain, and fatigue. The quality of
      the studies was evaluated using Cochrane Collaboration Guidelines. The effect
      size on outcome indicators used the formula devised by Hedges and Olkin (1985).
      RESULTS: Results showed that music interventions were significantly effective in
      ameliorating anxiety (g = -0.553), depression (g = -0.510), pain (g = -0.656),
      and fatigue (g = -0.422) in cancer patients. Subgroup analyses revealed that age
      and who selected the music were major factors influencing the effect size on
      anxiety reduction. CONCLUSIONS: Music interventions significantly ameliorate
      anxiety, depression, pain, and fatigue in cancer patients, especially adults.
      Music interventions were more effective in adults than in children or adolescents
      and more effective when patients, rather than researchers, chose the music.
      IMPLICATIONS FOR PRACTICE: Our findings provide important information for future
      music-intervention planners to improve the design and processes that will benefit
      patients in such programs.

PMID- 24662724
TI  - EphrinB2 affects apical constriction in Xenopus embryos and is regulated by
      ADAM10 and flotillin-1.
AB  - The Eph/ephrin signalling pathways have a critical function in cell adhesion and
      repulsion, and thus play key roles in various morphogenetic events during
      development. Here we show that a decrease in ephrinB2 protein causes neural tube
      closure defects during Xenopus laevis embryogenesis. Such a decrease in ephrinB2
      protein levels is observed on the loss of flotillin-1 scaffold protein, a newly
      identified ephrinB2-binding partner. This dramatic decline in ephrinB2 protein
      levels on the absence of flotillin-1 expression is specific, and is partly the
      result of an increased susceptibility to cleavage by the metalloprotease ADAM10.
      These findings indicate that flotillin-1 regulates ephrinB2 protein levels
      through ADAM10, and is required for appropriate neural tube morphogenesis in the
      Xenopus embryo. 

PMID- 24662725
TI  - A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for
      osteochondral tissue engineering.
AB  - Osteochondral injuries remain difficult to repair. We developed a novel photo
      cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was
      rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and
      was kept gelled for 3 weeks submerged in saline at 37 degrees C. When bone marrow
      derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose
      Bengal, approximately 87% of the cells were viable in the hydrogel at 24 h after
      photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained
      for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was
      retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was
      subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit
      osteochondral defect model. In both cases, the defect was repaired with articular
      cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross
      linkable gelatin appears to be a promising scaffold for the treatment of
      osteochondral injury.

PMID- 24662726
TI  - Tremella Polysaccharides attenuated sepsis through inhibiting abnormal
      CD4+CD25(high) regulatory T cells in mice.
AB  - Tremella Polysaccharides (TPS) have been reported to play an important role in
      regulating immune responses. Tregs are widely identified as the critical reason
      for immune dysfunction during sepsis. However, whether TPS could influence the
      immunomodulatory activities of Tregs in post-burn sepsis mice remains unclear. In
      this experiment, we researched the effects of TPS on peripheral blood Tregs in
      sepsis mouse induced by burn plus Pseudomonas aeruginosa infection. Results
      showed that TPS reversed the influences of Tregs on CD4+T cells proliferation and
      polarization and declined the level of IL-10 in burn plus P. aeruginosa infection
      mice. In addition, TPS notably reduced the mortality of post-burn sepsis mice.
      Therefore, TPS could inhibit the abnormal activities of CD4+CD25(high) Tregs in
      burn with P. aeruginosa infection mice, at least in part via inhibiting IL-10
      secretion, and trigger a shift of Th2 to Th1 with activation of CD4+T cells in
      burn with P. aeruginosa infection mice.

PMID- 24662727
TI  - In vivo effects of 17beta-estradiol on cardiac Na(+)/K(+)-ATPase expression and
      activity in rat heart.
AB  - In this study the in vivo effects of estradiol in regulating Na(+)/K(+)-ATPase
      function in rat heart was studied. Adult male Wistar rats were treated with
      estradiol (40MUg/kg, i.p.) and after 24h the animals were sacrificed and the
      heart excised. Following estradiol administration, cardiac Na(+)/K(+)-ATPase
      activity, expression of the alpha1 subunit, and phosphorylation of the alpha1
      subunit were significantly increased. These animals also had significantly
      decreased levels of digoxin-like immunoreactive factor(s). Na(+) levels were also
      significantly reduced but to a level that was still within the normal
      physiological range, highlighting the ability of the Na(+)/K(+)-ATPase to balance
      the ionic composition following treatment with estradiol. Estradiol treated rats
      also showed increased phosphorylation of protein kinase B (Akt), and
      extracellular-signal-regulated kinase 1/2 (ERK1/2). We therefore suggest a role
      for Akt and/or ERK1/2 in estradiol-mediated regulation of cardiac Na(+)/K(+)
      ATPase expression and activity in rat heart. 

PMID- 24662728
TI  - Incontinence: artificial sphincter can't take the pressure.

PMID- 24662729
TI  - Prostate cancer: radiotherapy-treating patients in a fast-moving field.

PMID- 24662730
TI  - Prostate cancer: predicting high-risk prostate cancer-a novel stratification
      tool.
AB  - Currently, numerous systems exist for the identification of high-risk prostate
      cancer, but few of these systems can guide treatment strategies. A new
      stratification tool that uses common diagnostic factors can help to predict
      outcomes after radical prostatectomy. The tool aids physicians in the
      identification of appropriate candidates for aggressive, local treatment.

PMID- 24662731
TI  - Prostate cancer: Melbourne consensus-noble but misguided.
AB  - Unfortunately, the noble aims of the Melbourne Consensus statement on the early
      detection of prostate cancer lack rigour, failing to take into account the
      breadth of evidence in this field; as a result, they fall disappointingly short
      of providing clarity on this important issue.

PMID- 24662733
TI  - Retrospective studies on pediatric infective endocarditis over 40 years in a mid
      west area of China.
AB  - OBJECTIVE: We have evaluated 106 pediatric cases of infective endocarditis (IE)
      to elucidate clinical manifestations and pathogenic microorganism profiling of IE
      in China. METHODS: Clinical features, complications, pathogenic microorganisms,
      diagnosis and treatment of pediatric IE were reviewed in two groups of patients
      with IE from the different periods of time (group A, 34 cases obtained in the
      period from 2000 to 2011 and group B, 72 cases obtained in the period from 1964
      to 1999). RESULTS: A total of 106 pediatric patients with a definite diagnosis of
      IE based on the modified Duke criteria were enrolled and evaluated in this study.
      By comparing two groups of patients from different time periods, we found that
      the incidence of rheumatic heart disease was significantly reduced (from 19.4 to
      5.9%), whereas congenital heart disease-associated IE had a tendency to increase
      (from 55.6 to 79.4%). Staphylococcus aureus was detected as the most common
      pathogenic microorganism, and its involvement tended to increase (from 32.0 to
      58.5%), whereas the percentage of infections caused by Streptococcus viridans
      (8.0%) had not changed. It was interesting to note that the rate of vegetations
      detected was increased from 50.0 to 67.6% and the incidence of right-sided IE was
      also increased (from 35.0 to 60.9%). The most common valves involved in recent
      cases were tricuspid valves (increase from 30.0 to 47.8%), while mitral valve
      infection was reduced (from 60.0 to 39.1%). Penicillin was still the most
      commonly used antibiotic for the treatment of IE; the combination of penicillin
      plus cephalosporin has been recommended more and more recently. CONCLUSIONS:
      Comparing pediatric IE patients during the past 40 years, we found that the role
      of rheumatic heart disease as a predisposing factor is diminishing. Pediatric IE
      is still predominantly caused by staphylococci. The most commonly involved valves
      are tricuspid valves instead of mitral valves. Gram-positive bacteria showed an
      increased resistance to penicillin when used alone, and the use of combination
      treatment with antibiotics is increasing in the area.

PMID- 24662732
TI  - Cystinuria-a urologist's perspective.
AB  - Cystinuria is a genetic disease that leads to frequent formation of stones. In
      patients with recurrent stone formation, particularly patients <30 years old or
      those who have siblings with stone disease, urologists should maintain a high
      index of suspicion of the diagnosis of cystinuria. Patients with cystinuria
      require frequent follow-up and a multidisciplinary approach to diagnosis,
      prevention and management. Patients have reported success in preventing stone
      episodes by maintaining dietary changes using a tailored review from a specialist
      dietician. For patients who do not respond to conservative lifestyle measures,
      medical therapy to alkalinize urine and thiol-binding drugs can help. A pre
      emptive approach to the surgical management of cystine stones is recommended by
      treating smaller stones with minimally invasive techniques before they enlarge to
      a size that makes management difficult. However, a multimodal approach can be
      required for larger complex stones. Current cystinuria research is focused on
      methods of monitoring disease activity, novel drug therapies and genotype
      phenotype studies. The future of research is collaboration at a national and
      international level, facilitated by groups such as the Rare Kidney Stone
      Consortium and the UK Registry of Rare Kidney Diseases. 

PMID- 24662735
TI  - PTH [1-34]-induced alterations of the subchondral bone provoke early
      osteoarthritis.
AB  - OBJECTIVE: To test the hypothesis that changes in the subchondral bone induced by
      parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the
      articular cartilage within a naive osteochondral unit in vivo. DESIGN: Daily
      subcutaneous injections of 10 MUg PTH [1-34]/kg were given to adult rabbits for 6
      weeks, controls received saline. Blood samples were continuously collected to
      monitor renal function. The subchondral bone plate and subarticular spongiosa of
      the femoral heads were separately assessed by micro-computed tomography.
      Articular cartilage was evaluated by macroscopic and histological osteoarthritis
      scoring, polarized light microscopy, and immunohistochemical determination of
      type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3
      expression. Absolute and relative extents of hyaline and calcified articular
      cartilage layers were measured histomorphometrically. The correlation between PTH
      induced changes in subchondral bone and articular cartilage was determined.
      RESULTS: PTH [1-34] enhanced volume, mineral density, and trabecular thickness
      within the subarticular spongiosa, and increased thickness of the calcified
      cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface
      irregularities and reduced matrix staining (both P < 0.03). These early
      osteoarthritic changes correlated with and were ascribed to the increased
      thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral
      density of the subarticular spongiosa (P = 0.001). CONCLUSIONS: Modifications of
      the subarticular spongiosa by PTH [1-34] cause broadening of the calcified
      cartilage layer, resulting in osteoarthritic cartilage degeneration. These
      findings identify a mechanism by which PTH-induced alterations of the normal
      subchondral bone microarchitecture may provoke early osteoarthritis.

PMID- 24662734
TI  - Trajectories and risk profiles of pain in persons with radiographic, symptomatic
      knee osteoarthritis: data from the osteoarthritis initiative.
AB  - BACKGROUND: Little is known about the temporal evolution of pain severity in
      persons with knee osteoarthritis (OA). We sought to describe the pain trajectory
      over 6 years in a cohort of subjects with radiographic, symptomatic knee OA.
      METHODS: We used data from the Osteoarthritis Initiative (OAI), a multi-center,
      longitudinal study of subjects with diagnosed radiographic evidence of knee OA.
      Pain was assessed at baseline and annually for 6 years. Our analysis cohort
      included subjects with symptomatic knee OA at baseline, defined as baseline
      Kellgren-Lawrence (KL) score >=2 with Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) pain score >0. We used group-based trajectory
      modeling to identify distinct patterns of pain progression over a 6-year follow
      up. Factors examined included sex, race, education, comorbidities, age, body mass
      index (BMI), alignment, KL grade, and depression. RESULTS: We used data from 1753
      OAI participants with symptomatic knee OA. Mean baseline WOMAC pain score was
      26.5 (0-100, 100=worst) with standard deviation (SD) 19. Group-based trajectory
      modeling identified five distinct pain trajectories; baseline pain scores for
      each ranged from 15 to 62. None of the trajectories exhibited substantial
      worsening. One fifth of subjects in the two trajectories with the greatest pain
      underwent total knee replacement (TKR) over follow-up. Higher KL grade, obesity,
      depression, medical comorbidities, female sex, non-white race, lower education,
      and younger age were associated with trajectories characterized by greater pain.
      CONCLUSION: We found that knee pain changes little, on average, over 6 years in
      most subjects. These observations suggest knee OA is characterized by persistent
      rather than inexorably worsening symptoms.

PMID- 24662736
TI  - An epigenetic screen unmasks metallothioneins as putative contributors to renal
      cell carcinogenesis.
AB  - OBJECTIVE: Functional epigenetic studies aimed to re-express transcriptionally
      silenced genes in renal cell carcinoma (RCC) may facilitate the ongoing search
      for appropriate markers supporting clinical decision-making. METHODS: The RCC
      cell line A-498 was treated with the DNA methyltransferase inhibitor zebularine
      under low-cytotoxicity conditions. RNA chip analyses revealed several upregulated
      transcripts that were further validated by qPCR on 49 matched pairs of human
      kidney tissues to identify suitable marker candidates. RESULTS: Members of the
      metallothionein (MT) group were remarkably downregulated in tumor tissues. MT1G
      and MT1H expression was decreased in 98% of cases, whereas MT2A expression was
      downregulated in 73% of all cases. Comparison of 308 reactivated transcripts
      upregulated more than 1.5-fold to published data revealed a high number of shared
      candidates, which supports the consistency of this experimental approach.
      CONCLUSION: MTs were found to be transcriptionally inactivated in human RCC. Our
      observations support the hypothesis of a possible involvement of these
      metalloproteins in renal cell carcinogenesis. Additional functional studies of
      these genes may provide clues for understanding renal cancers as essentially
      metabolic diseases.

PMID- 24662737
TI  - Endobronchial intubation after correction of swan neck deformity of the cervical
      spine.

PMID- 24662738
TI  - Targeted cervical epidural blood patch for the management of refractory headache
      in a patient with spontaneous intracranial hypotension.

PMID- 24662739
TI  - Therapeutic hypothermia after cardiac arrest during craniotomy.

PMID- 24662740
TI  - About Bill Young: a personal note.

PMID- 24662741
TI  - Intra-arterial etomidate for provocative testing in embolization procedure for
      cerebral arteriovenous malformation.

PMID- 24662742
TI  - Interleukin-6 modulation of intestinal epithelial tight junction permeability is
      mediated by JNK pathway activation of claudin-2 gene.
AB  - Defective intestinal epithelial tight junction (TJ) barrier has been shown to be
      a pathogenic factor in the development of intestinal inflammation. Interleukin-6
      (IL-6) is a pleiotropic, pro-inflammatory cytokine which plays an important role
      in promoting inflammatory response in the gut and in the systemic circulation.
      Despite its key role in mediating variety inflammatory response, the effect of IL
      6 on intestinal epithelial barrier remains unclear. The purpose of this study was
      to investigate the effect of IL-6 on intestinal epithelial TJ barrier and to
      delineate the intracellular mechanisms involved using in-vitro (filter-grown Caco
      2 monolayers) and in-vivo model (mouse intestinal perfusion) systems. Our results
      indicated that IL-6 causes a site-selective increase in Caco-2 intestinal
      epithelia TJ permeability, causing an increase in flux of small-sized molecules
      having molecular radius <4 A. The size-selective increase in Caco-2 TJ
      permeability was regulated by protein-specific increase in claudin-2 expression.
      The IL-6 increase in TJ permeability required activation of JNK signaling
      cascade. The JNK pathway activation of AP-1 resulted in AP-1 binding to its
      binding sequence on the claudin-2 promoter region, leading to promoter activation
      and subsequent increase in claudin-2 gene transcription and protein synthesis and
      TJ permeability. Our in-vivo mouse perfusion showed that IL-6 modulation of mouse
      intestinal permeability was also mediated by AP-1 dependent increase in claudin-2
      expression. In conclusion, our studies show for the first time that the IL-6
      modulation of intestinal TJ permeability was regulated by JNK activation of AP-1
      and AP-1 activation of claudin-2 gene. 

PMID- 24662744
TI  - Multiple breath washout becoming feasible for the assessment of lung function in
      infants and young children with cystic fibrosis in a clinical setting.

PMID- 24662743
TI  - Intestinal parasitic infections in HIV-infected patients, Lao People's Democratic
      Republic.
AB  - BACKGROUND: HIV infection is an emerging problem in Laos. We conducted the first
      prospective study on intestinal parasites, including opportunistic protozoa, in
      newly diagnosed HIV infected patients, with or without diarrhea. The aims were to
      describe the spectrum of infections, to determine their prevalence and to assess
      their associations with diarrhea, CD4 cell count, place of residence and living
      conditions. METHODOLOGY: One to three stool samples over consecutive days were
      obtained from 137 patients. The Kato thick smear method, formalin-ethyl
      concentration and specific stains for coccidia and microsporidia diagnosis were
      performed on 260 stool samples. Baseline characteristics regarding relevant
      demographics, place of residence and living conditions, clinical features
      including diarrhea, were collected using a standardized questionnaire. PRINCIPAL
      FINDINGS: The 137 patients were young (median age: 36 years) and severely
      immunocompromised (83.9% at WHO stage 3 or 4, median CD4 cell count: 41/mm3).
      Diarrhea was present in 43.0% of patients. Parasite infection was found in 78.8%
      of patients, infection with at least two species in 49.6%. Prevalence rates of
      protozoan and helminth infections were similar (54.7% and 58.4% respectively).
      Blastocystis sp. was the most frequent protozoa (26.3%). Cryptosporidium sp.,
      Cytoisospora belli and microsporidia, found at low prevalence rates (6.6%, 4.4%,
      2.9%, respectively), were described for the first time in Laos. Cryptosporidium
      sp. was associated with persistent diarrhea. Strongyloides stercoralis was the
      most prevalent helminth following Opisthorchis viverrini (20.4% and 47.5%
      respectively). The most immunocompromised patients, as assessed by a CD4 count <=
      50 cells/mm3, were more likely to be infected with intestinal parasites.
      CONCLUSIONS/SIGNIFICANCE: HIV infection was mainly diagnosed at an advanced stage
      of immunosuppression in Lao patients. Intestinal parasite infections were highly
      prevalent regardless of their diarrheal status. Opportunistic infections were
      reported. Improving the laboratory diagnosis of intestinal parasite infections
      and the knowledge on their local risk factors is warranted.

PMID- 24662745
TI  - Calculation of action potential propagation in nerve fiber.
AB  - This article introduces generalization of the action potential spreading model
      which considers generation of the action potential in each segment of the nerve
      fiber. Behavior of the impulse signal waveform during the propagation process was
      analyzed. A mechanism of distributed generation of the charge in nerve fiber
      results in decrease of phase velocity of signal spreading rate. Amplitude of the
      action potential decreases and pulse width increases in the action potential
      propagation process. 

PMID- 24662746
TI  - Activated androgen receptor promotes bladder cancer metastasis via Slug mediated
      epithelial-mesenchymal transition.
AB  - Androgen receptor (AR) has been indicated to be involved in bladder cancer
      progression. We showed androgen induced epithelial-mesenchymal transition (EMT)
      in AR-positive bladder cancer cells and promoted tumor metastasis in xenograft
      models. We subsequently identified that Slug was the mediator of EMT induced by
      androgen. Furthermore, upregulation of Slug was due to activation of Wnt/beta
      catenin signaling in response to androgen. Finally, expression of AR showed
      strong correlation with loss of E-cadherin, higher expression of Slug and nuclear
      accumulation of beta-catenin in bladder tumor tissues. Taken together, our
      results suggest AR signaling promotes bladder cancer metastasis through Slug
      mediated EMT. 

PMID- 24662748
TI  - Dimethylformamide interferes with Coomassie dye staining of proteins on blue
      native gel electrophoresis.
AB  - Blue native gel electrophoresis (BN-PAGE) is used extensively for
      characterization of mitochondrial respiratory complexes and uses the binding of
      Coomassie brilliant blue G-250 to visualize proteins. Oxidative modification of
      sulfhydryl groups of such proteins can be evaluated by labeling with
      iodoacetamide conjugated to biotin (BIAM) and detected with streptavidin
      peroxidase on Western blots following BN-PAGE. However, dissolving BIAM in
      dimethylformamide, a recommended solvent, reduces Coomassie blue G staining to
      proteins during BN-PAGE. This interference is prevented by dissolving BIAM in
      dimethyl sulfoxide. Precautions in the use of the dye for protein staining
      subsequent to BIAM labeling are discussed. 

PMID- 24662747
TI  - Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the
      death receptor pathway.
AB  - The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) causes cancer
      cell death, but many cancers, including pancreatic cancer, are resistant to TRAIL
      therapy. A combination of TRAIL and the diterpene triepoxide, triptolide, is
      effective in inducing pancreatic cancer cell death. Triptolide increases levels
      of death receptor DR5 and decreases the pro-survival FLICE-like inhibitory
      protein (c-FLIP), which contribute to the activation of caspase-8. This
      combination further causes both lysosomal and mitochondrial membrane
      permeabilization, resulting in cell death. Our study provides a mechanism by
      which triptolide sensitizes TRAIL resistant cells, which may become a novel
      therapeutic strategy against pancreatic cancer. 

PMID- 24662749
TI  - Effects of LPS and dietary free fatty acids on MCP-1 in 3T3-L1 adipocytes and
      macrophages in vitro.
AB  - BACKGROUND: High levels of free fatty acids (FFA) have been suggested to be one
      of the underlying mechanisms for adipose tissue (AT) inflammation and dysfunction
      in obesity. Human AT produces several adipokines including monocyte
      chemoattractant protein-1 (MCP-1), which are involved in the pathogenesis of
      obesity-mediated inflammation. OBJECTIVE: In this study, we investigated the
      effects of lipopolysaccharide (LPS) and a panel of dietary FFA on MCP-1 gene and
      protein expression in adipocytes and macrophages. Furthermore, we investigated
      whether the effect of LPS and FFA were mediated through the toll-like receptor 4
      (TLR4). METHODS: 3T3-L1 adipocytes and THP-1 macrophages were incubated for 24 h
      with the following FFA: monounsaturated fatty acid (oleic acid), saturated fatty
      acid (palmitic acid) and trans fatty acid (elaidic acid; 500 MUM) with and
      without LPS (2 ng ml(-1)), and MCP-1 and TLR4 mRNA expression and MCP-1 protein
      secretion was determined. RESULTS: The results showed that LPS significantly
      increased MCP-1 and TLR4 expression and MCP-1 secretion in 3T3-L1 adipocytes, and
      that the MCP-1 expression was blocked by a TLR4 inhibitor (CLI095). The effects
      of the various FFA on MCP-1 mRNA expression and protein secretion in the
      adipocytes showed no significant changes either alone or in combination with LPS.
      In macrophages, palmitic acid increased MCP-1 mRNA expression by 1.8-fold
      (P<0.05), but oleic acid and elaidic acid had no effects. CONCLUSIONS: In
      conclusion, in 3T3-L1 adipocyte, the TLR4-agonist, LPS, stimulates the
      proinflammatory chemokine MCP-1. The different classes of FFA did not induce MCP
      1 mRNA expression or protein secretion in the adipocytes, but the saturated FFA,
      palmitic acid, induced MCP-1 mRNA expression in macrophages, possibly because of
      the higher expression level of TLR4 in the macrophages than the adipocytes. Our
      results indicate that FFA may induce AT inflammation through proinflammatory
      stimulation of macrophages.

PMID- 24662750
TI  - Comparison of genome-wide association methods in analyses of admixed populations
      with complex familial relationships.
AB  - Population structure is known to cause false-positive detection in association
      studies. We compared the power, precision, and type-I error rates of various
      association models in analyses of a simulated dataset with structure at the
      population (admixture from two populations; P) and family (K) levels. We also
      compared type-I error rates among models in analyses of publicly available human
      and dog datasets. The models corrected for none, one, or both structure levels.
      Correction for K was performed with linear mixed models incorporating familial
      relationships estimated from pedigrees or genetic markers. Linear models that
      ignored K were also tested. Correction for P was performed using principal
      component or structured association analysis. In analyses of simulated and real
      data, linear mixed models that corrected for K were able to control for type-I
      error, regardless of whether they also corrected for P. In contrast, correction
      for P alone in linear models was insufficient. The power and precision of linear
      mixed models with and without correction for P were similar. Furthermore, power,
      precision, and type-I error rate were comparable in linear mixed models
      incorporating pedigree and genomic relationships. In summary, in association
      studies using samples with both P and K, ancestries estimated using principal
      components or structured assignment were not sufficient to correct type-I errors.
      In such cases type-I errors may be controlled by use of linear mixed models with
      relationships derived from either pedigree or from genetic markers. 

PMID- 24662751
TI  - Risk factors for proliferative diabetic retinopathy in a Latino American
      population.
AB  - PURPOSE: To assess the personal and demographic risk factors for proliferative
      diabetic retinopathy in Latino Americans in Los Angeles County. METHODS: In this
      prospective, non-interventional, cross-sectional case control study, seven
      hundred and twenty-nine subjects from Los Angeles County University of Southern
      California Medical Center (LAC + USC), Los Angeles, CA, were enrolled. All
      patients were recruited prospectively from the LAC + USC Medical Center and
      affiliated clinics between June 2008 and June 2011. Complete personal data and
      results from systemic and ophthalmic examinations were collected for all enrolled
      subjects. Laboratory tests such as glycosylated hemoglobin, creatinine levels,
      and cholesterol levels were collected prospectively by drawing blood at the time
      of each patient's clinic visit. The main outcome measures were age, gender, type
      of diabetes mellitus (DM I or II) duration of diabetes mellitus, history of
      hypertension, history of insulin use, height, weight, and body mass index,
      smoking history, glycosylated hemoglobin, creatinine levels, and cholesterol
      levels. RESULTS: The mean age of subjects with no diabetic retinopathy was 56.38
      years (SD, 10.16), whereas that of patients with proliferative diabetic
      retinopathy was 57.43 years (SD, 9.63). Parameters that conferred a statistically
      significant increased risk for proliferative diabetic retinopathy in the
      multivariate model included gender (men were at higher risk: odds ratio [OR],
      4.11; 95% confidence interval [CI], 2.56-6.58), insulin use (OR, 1.85; 95% CI,
      1.13-3.03), history of hypertension (OR, 1.64; 95% CI, 1.02-2.63), and duration
      (>25 years vs. 10-15 years) of diabetes (OR, 22.00; 95% CI, 9.76-49.60).
      CONCLUSION: In this case-control study in a Latino population, duration of
      diabetes and male gender were the strongest risk factor for the development of
      proliferative diabetic retinopathy followed by insulin use and hypertension.
      Interestingly, smoking and glycosylated hemoglobin levels did not confer
      additional significant risk in this cohort.

PMID- 24662752
TI  - Regulation of Sox6 by cyclin dependent kinase 5 in brain.
AB  - Cyclin dependent kinase 5 (Cdk5) is a proline-directed Ser/Thr kinase involved in
      various biological functions during normal brain development and
      neurodegeneration. In brain, Cdk5 activity is specific to post-mitotic neurons,
      due to neuronal specific expression of its activator p35. The biological
      functions of Cdk5 have been ascribed to its cytoplasmic substrates, however not
      much is known in nucleus. Here, we show that nuclear transcription factor Sox6 is
      a direct nuclear target of Cdk5. Sox6 is expressed in Tuj1 positive neurons,
      suggesting that Sox6 is expressed in differentiating neurons. The expression of
      Sox6 is high in mitotic nuclei during embryonic day 12 (E12) and gradually
      decreases during development into adult. On the other hand, Cdk5 expression
      gradually increases during its development. We show that Sox6 is expressed in
      mitotic nuclei in embryonic day 12 (E12) and in migrating neurons of E16. Sox6 is
      phosphorylated in vivo. Sox6 was detected by phospho-Ser/Thr and phospho-Ser/Thr
      Pro and MPM-2 (Mitotic protein #2) antibodies in brain. Furthermore, calf
      intestinal alkaline phosphatase (CIAP) digestion resulted in faster migration of
      Sox6 band. The GST-Sox6 was phosphorylated by Cdk5/p35. The mass spectrometry
      analysis revealed that Sox6 is phosphorylated at T119PER motif. We show that Sox6
      steady state levels are regulated by Cdk5. Cdk5 knockout mice die in utero and
      Sox6 protein expression is remarkably high in Cdk5-/- brain, however, there is no
      change in mRNA expression, suggesting a post-translational regulation of Sox6 by
      Cdk5. Transfection of primary cortical neurons with WT Cdk5 reduced Sox6 levels,
      while dominant negative (DN) Cdk5 and p35 increased Sox6 levels. Thus, our
      results indicate that Cdk5 regulates Sox6 steady state protein level that has an
      important role in brain development and function. 

PMID- 24662754
TI  - DFT simulation, quantum chemical electronic structure, spectroscopic and
      structure-activity investigations of 2-benzothiazole acetonitrile.
AB  - The Fourier transform infrared and FT-Raman spectra of 2-benzothiazole
      acetonitrile (BTAN) have been recorded in the range 4000-450 and 4000-100 cm(-1)
      respectively. The conformational analysis of the compound has been carried out to
      obtain the stable geometry of the compound. The complete vibrational assignment
      and analysis of the fundamental modes of the compound are carried out using the
      experimental FTIR and FT-Raman data and quantum chemical studies. The
      experimental vibrational frequencies are compared with the wavenumbers derived
      theoretically by B3LYP gradient calculations employing the standard 6-31G(**),
      high level 6-311++G(**) and cc-pVTZ basis sets. The structural parameters,
      thermodynamic properties and vibrational frequencies of the normal modes obtained
      from the B3LYP methods are in good agreement with the experimental data. The (1)H
      (400 MHz; CDCl3) and (13)C (100 MHz;CDCl3) nuclear magnetic resonance (NMR)
      spectra are also recorded. The electronic properties, the energies of the highest
      occupied and lowest unoccupied molecular orbitals are measured by DFT approach.
      The kinetic stability of the molecule has been determined from the frontier
      molecular orbital energy gap. The charges of the atoms and the structure-chemical
      reactivity relations of the compound are determined by its chemical potential,
      global hardness, global softness, electronegativity, electrophilicity and local
      reactivity descriptors by conceptual DFT methods. The non-linear optical
      properties of the compound have been discussed by measuring the polarisability
      and hyperpolarisability tensors.

PMID- 24662755
TI  - Effect of aggregated silver nanoparticles on luminol chemiluminescence system and
      its analytical application.
AB  - We found that after silver nanoparticles (AgNPs) aggregated, its catalytic
      activity on luminol CL reaction obviously changed, and the change characteristic
      was closely related to the sizes of AgNPs. UV-visible spectra, X-ray
      photoelectron spectra, zeta potential and transmission electron microscopy
      studies were carried out to investigate the CL effect mechanism. The different CL
      responses of aggregated AgNPs with different size were suggested to be due to the
      two effects of quantum size and electron density in nanoparticle's conduction
      bands, and which one played a major role. The poisonous organic contaminants such
      as anilines, could induce the aggregation of AgNPs, were observed to affect
      effectively the luminol-H2O2-7 nm and 15 nm AgNPs CL systems and were detectable
      by use of a flow injection method with the enhanced or inhibited CL detection.

PMID- 24662756
TI  - Application of time-resolved fluorescence to the determination of metabolites.
AB  - A simple fluorescent methodology for the simultaneous determination of two major
      metabolites of acetylsalicylic acid--salicylic and gentisic acids--in
      pharmaceutical preparations and human urine is proposed. Due to the overlapping
      between the fluorescence spectra of both analytes, the use of the more selective
      fluorescence decay curves is proposed. Values of dependent instrumental variables
      affecting the signal-to-noise ratio were fixed with a simplex optimization
      procedure. A calibration matrix of thirteen standards plus two blank samples was
      processed using a partial least-squares (PLS) analysis. To assess the goodness of
      the proposed method, a prediction set of nine synthetic samples was analyzed,
      obtaining recovery percentages between 95% and 106%. Limits of detection,
      calculated by means of a new criterion, were 3.49 MUg L(-1) and 1.66 MUg L(-1)
      for salicylic and gentisic acids, respectively. The method was also tested in
      three pharmaceutical preparations containing salicylic acid, obtaining recovery
      percentages close to 100%. Finally, the simultaneous determination of both
      analytes in human urine samples was successfully carried out by the PLS-analysis
      of a matrix of thirteen standards plus five analyte blanks. Although spectra of
      analytes and urine overlap strongly, no extraction method neither prior
      separation of the analytes were needed.

PMID- 24662757
TI  - Vibrational spectroscopy (FT-IR and Laser-Raman) investigation, and computational
      (M06-2X and B3LYP) analysis on the structure of 4-(3-fluorophenyl)-1-(propan-2
      ylidene)-thiosemicarbazone.
AB  - In this study, the experimental and theoretical vibrational spectral analysis of
      4-(3-fluorophenyl)-1-(propan-2-ylidene)-thiosemicarbazone have been carried out.
      The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(
      1)) have been recorded for the solid state samples. The theoretical vibrational
      frequencies and the optimized geometric parameters (bond lengths and angles) have
      been calculated for gas phase using density functional theory (DFT/B3LYP: Becke,
      3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical
      exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis
      set. The diversity in molecular geometry of fluorophenyl substituted
      thiosemicarbazones has been discussed based on the X-ray crystal structure
      reports and theoretical calculation results from the literature. The assignments
      of the vibrational frequencies have been done on the basis of potential energy
      distribution (PED) analysis by using VEDA4 software. A good correlation was found
      between the computed and experimental geometric and vibrational data. In
      addition, the highest occupied (HOMO) and lowest unoccupied (LUMO) molecular
      orbital energy levels and other related molecular energy values of the compound
      have been determined using the same level of theoretical calculations.

PMID- 24662753
TI  - Comparative expression study of the endo-G protein coupled receptor (GPCR)
      repertoire in human glioblastoma cancer stem-like cells, U87-MG cells and non
      malignant cells of neural origin unveils new potential therapeutic targets.
AB  - Glioblastomas (GBMs) are highly aggressive, invasive brain tumors with bad
      prognosis and unmet medical need. These tumors are heterogeneous being
      constituted by a variety of cells in different states of differentiation. Among
      these, cells endowed with stem properties, tumor initiating/propagating
      properties and particularly resistant to chemo- and radiotherapies are designed
      as the real culprits for tumor maintenance and relapse after treatment. These
      cells, termed cancer stem-like cells, have been designed as prominent targets for
      new and more efficient cancer therapies. G-protein coupled receptors (GPCRs), a
      family of membrane receptors, play a prominent role in cell signaling, cell
      communication and crosstalk with the microenvironment. Their role in cancer has
      been highlighted but remains largely unexplored. Here, we report a descriptive
      study of the differential expression of the endo-GPCR repertoire in human
      glioblastoma cancer stem-like cells (GSCs), U-87 MG cells, human astrocytes and
      fetal neural stem cells (f-NSCs). The endo-GPCR transcriptome has been studied
      using Taqman Low Density Arrays. Of the 356 GPCRs investigated, 138 were retained
      for comparative studies between the different cell types. At the transcriptomic
      level, eight GPCRs were specifically expressed/overexpressed in GSCs. Seventeen
      GPCRs appeared specifically expressed in cells with stem properties (GSCs and f
      NSCs). Results of GPCR expression at the protein level using mass spectrometry
      and proteomic analysis are also presented. The comparative GPCR expression study
      presented here gives clues for new pathways specifically used by GSCs and unveils
      novel potential therapeutic targets. 

PMID- 24662758
TI  - Photocatalytic degradation of an azo dye Sunset Yellow under UV-A light using
      TiO2/CAC composite catalysts.
AB  - The photocatalytic activity and the promoting effect of titania (TiO2) by
      commercial activated carbon (CAC) for removing the pollutant in wastewater were
      investigated. The TiO2/CAC composite photocatalysts with various ratios of CAC to
      TiO2 were prepared by sol-gel method. The catalyst was characterized by X-ray
      diffraction (XRD), high resolution scanning electron microscope (HR-SEM), energy
      dispersive spectra (EDS), diffuse reflectance spectra (DRS), photoluminescence
      spectra (PL), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller
      (BET) surface area measurement methods. The photocatalytic activity of TiO2/CAC
      was investigated for the degradation of Sunset Yellow (SY) in aqueous solution
      using UV-A light. The TiO2/CAC is found to be more efficient than prepared TiO2
      and TiO2-P25 at pH 7 for the mineralization of SY. The synergism between TiO2 and
      CAC may increase the catalytic activity. The effects of operational parameters
      such as the amount of photocatalyst, dye concentration and initial pH on photo
      mineralization of SY have been analyzed. The mineralization of SY has been
      confirmed by COD measurements. The catalyst is found to be reusable. 

PMID- 24662759
TI  - Vibrational spectroscopy investigation using M06-2X and B3LYP methods analysis on
      the structure of 2-Trifluoromethyl-10H-benzo[4,5]-imidazo[1,2-a]pyrimidin-4-one.
AB  - In this study, the experimental and theoretical vibrational frequencies of a
      newly synthesized bioactive agent namely, 2-Trifluoromethyl-10H-benzo[4,5]
      imidazo[1,2-a]pyrimidin-4-one (TIP) have been investigated. The experimental FT
      IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in
      solid phase have been recorded. The theoretical vibrational frequencies and the
      optimized geometric parameters (bond lengths and bond angles) have been
      calculated using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee
      Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation
      function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09W
      software, for the first time. The assignments of the vibrational frequencies have
      been done by potential energy distribution (PED) analysis using VEDA 4 software.
      The theoretical optimized geometric parameters and vibrational frequencies have
      been found to be in good agreement with the corresponding experimental data and
      results in the literature. In addition, the highest occupied molecular orbital
      (HOMO) energy, the lowest unoccupied molecular orbital (LUMO) energy and the
      other related molecular energy values of the compound have been investigated
      using the same theoretical calculations.

PMID- 24662760
TI  - Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of 2,3,4,5,6
      Pentafluoro-trans-cinnamic acid.
AB  - In this study, the experimental and theoretical vibrational frequencies of a
      newly synthesized 2,3,4,5,6-Pentafluoro-trans-cinnamic acid have been
      investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra
      (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The
      theoretical vibrational frequencies and optimized geometric parameters (bond
      lengths and bond angles) have been calculated by using density functional theory
      (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and DFT/M06-2X (the highly
      parameterized, empirical exchange correlation function) quantum chemical methods
      with 6-311++G(d,p) basis set by Gaussian 09W software, for the first time. The
      assignments of the vibrational frequencies have been done by potential energy
      distribution (PED) analysis by using VEDA 4 software. The theoretical optimized
      geometric parameters and vibrational frequencies have been found to be in good
      agreement with the corresponding experimental data, and with the results in the
      literature. In addition, the highest occupied molecular orbital (HOMO) and the
      lowest unoccupied molecular orbital (LUMO) energies and the other related
      molecular energy values have been calculated and depicted.

PMID- 24662761
TI  - Development and validation of simultaneous spectrophotometric and TLC
      spectrodensitometric methods for determination of beclomethasone dipropionate and
      salbutamol in combined dosage form.
AB  - Spectrophotometric and TLC-spectrodensitometric methods were developed and
      validated for the simultaneous determination of beclomethasone dipropionate (BEC)
      and salbutamol (SAL). The spectrophotometric methods include dual wavelength,
      ratio difference, constant center coupled with a novel method namely, spectrum
      subtraction and mean centering with mean percentage recoveries and RSD 99.72+/
      1.07 and 99.70+/-1.12, 100.25+/-1.12 and 99.89+/-1.12, 99.66+/-1.85 and 99.19+/
      1.32, 100.74+/-1.26 and 101.06+/-0.90 for BEC and SAL respectively. The TLC
      spectrodensitometric method was based on separation of both drugs on TLC aluminum
      plates of silica gel 60 F254, using benzene: methanol: triethylamine (10:1.5:0.5
      v/v/v) as a mobile phase, followed by densitometric measurements of their bands
      at 230 nm. The mean percentage recoveries and RSD were 99.07+/-1.25 and 101.35+/
      1.50 for BEC and SAL respectively. The proposed methods were validated according
      to ICH guidelines and were applied for the simultaneous analysis of the cited
      drugs in synthetic mixtures and pharmaceutical preparation. The methods were
      found to be rapid, specific, precise and accurate and can be successfully applied
      for the routine analysis of BEC and SAL in their pharmaceutical formulation with
      no need for prior separation. The results obtained were statistically compared to
      each other and to that of the reported HPLC method. The statistical comparison
      showed that there is no significant difference regarding both accuracy and
      precision.

PMID- 24662762
TI  - Theoretical and experimental investigation of photophysical properties of Zn(DFP
      SAMQ)2.
AB  - Theoretical calculations and experimental measurements were carried out for the
      investigation of spectroscopic and photophysical properties of Zn(DFP SAMQ)2
      complex. The rate constant of intersystem crossing and the radiative rate
      constant were calculated using ab initio method. The rate constant of the
      internal conversion was estimated using the received calculated values and the
      experimental fluorescence quantum yield. It was shown that the main mechanism for
      the deactivation of the excited electronic energy of the first singlet excited
      state is the process of internal conversion. 

PMID- 24662763
TI  - Tuning Piezo ion channels to detect molecular-scale movements relevant for fine
      touch.
AB  - In sensory neurons, mechanotransduction is sensitive, fast and requires
      mechanosensitive ion channels. Here we develop a new method to directly monitor
      mechanotransduction at defined regions of the cell-substrate interface. We show
      that molecular-scale (~13 nm) displacements are sufficient to gate
      mechanosensitive currents in mouse touch receptors. Using neurons from knockout
      mice, we show that displacement thresholds increase by one order of magnitude in
      the absence of stomatin-like protein 3 (STOML3). Piezo1 is the founding member of
      a class of mammalian stretch-activated ion channels, and we show that STOML3, but
      not other stomatin-domain proteins, brings the activation threshold for Piezo1
      and Piezo2 currents down to ~10 nm. Structure-function experiments localize the
      Piezo modulatory activity of STOML3 to the stomatin domain, and higher-order
      scaffolds are a prerequisite for function. STOML3 is the first potent modulator
      of Piezo channels that tunes the sensitivity of mechanically gated channels to
      detect molecular-scale stimuli relevant for fine touch. 

PMID- 24662764
TI  - Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced
      oxidative stress response: a possible mechanism for melanocyte degeneration in
      vitiligo.
AB  - Vitiligo melanocytes possess higher susceptibility to oxidative insults.
      Consistent with this, impairment of the antioxidant defense system has been
      reported to be involved in the onset and progression of vitiligo. Our previous
      study showed that the nuclear factor E2-related factor 2-antioxidant response
      element (Nrf2-ARE) pathway and its downstream antioxidant enzyme heme oxygenase-1
      (HO-1) are crucial for melanocytes to cope with H2O2-induced oxidative damage.
      Here, we sought to determine whether the diminished Nrf2-ARE activity that
      contributes to reduced downstream antioxidant enzymes and increased oxidative
      stress could be the reason why melanocytes are more vulnerable to vitiligo. We
      found that vitiligo melanocytes exhibited hypersensitivity to H2O2-induced
      oxidative injury because of reduced Nrf2 nuclear translocation and
      transcriptional activity, which led to decreased HO-1 expression and aberrant
      redox balance. Moreover, we also found that the level of serum HO-1 was
      significantly decreased and that of IL-2 was markedly increased in 113 vitiligo
      patients when compared with healthy controls. These data demonstrate that
      impaired activation of Nrf2 under oxidative stress could result in decreased
      expression of antioxidant enzymes and increased death of vitiligo melanocytes. 

PMID- 24662766
TI  - Loss of epidermal p38alpha signaling prevents UVR-induced inflammation via acute
      and chronic mechanisms.
AB  - UVB is a component of solar radiation primarily responsible for causing damage
      and cancer in irradiated skin, and disrupting immune homeostasis. The immediate
      harm and long-term health risks of excessive sunlight exposure are affecting the
      lives of nearly all people worldwide. Inflammation is a key mechanism underlying
      UVB's various detrimental effects. Here we show that activation of the protein
      kinase p38alpha is restricted to the epidermis in UVB-exposed skin, and that
      p38alpha ablation targeted to the epithelial compartment is sufficient to
      suppress UVB-induced inflammation. Mechanistically, loss of epithelial p38alpha
      signaling attenuates the expression of genes required to induce vascular leakage
      and edema, and also increases the steady-state abundance of epidermal gammadelta
      T cells, which are known to promote the repair of damaged epidermis. These
      effects of p38alpha deficiency delineate a molecular network operating at the
      organism-environment interface, and reveal conditions crucial to preventing the
      pathology resulting from sun-damaged skin. 

PMID- 24662765
TI  - DMBA/TPA treatment is necessary for BCC formation from patched deficient
      epidermal cells in Ptch(flox/flox)CD4Cre(+/-) mice.
AB  - The development of basal cell carcinoma (BCC), the most frequently diagnosed
      tumor among persons with European ancestry, is closely linked to mutations in the
      Hedgehog (Hh) receptor and tumor suppressor Patched1 (Ptch). Using
      Ptch(flox/flox)CD4Cre(+/-) mice, in which Ptch was ablated in CD4Cre-expressing
      cells, we demonstrate that the targeted cells can give rise to BCC after
      treatment with DMBA (7,12-dimethylbenz(a)anthracene)/TPA (12-O
      tetradecanoylphorbol-13-acetate), but not after wounding of the skin. In
      addition, in this model, BCC are not caused by malfunctioning of Ptch-deficient T
      cells, as BCC did not develop when bone marrow (BM) of Ptch(flox/flox)CD4Cre(+/-)
      mice was transplanted into Ptch wild-type mice. Instead, lineage-tracing
      experiments and flow cytometric analyses suggest that the tumors are initiated
      from rare Ptch-deficient stem cell-like cells of the epidermis that express CD4.
      As DMBA/TPA is a prerequisite for BCC development in this model, the initiated
      cells need a second stimulus for expansion and tumor formation. However, in
      contrast to papilloma, this stimulus seems to be unrelated to alterations in the
      Ras signaling cascade. Together, these data suggest that biallelic loss of Ptch
      in CD4(+) cells does not suffice for BCC formation and that BCC formation
      requires a second so far unknown event, at least in the Ptch(flox/flox)CD4Cre(+/
      ) BCC mouse model. 

PMID- 24662768
TI  - Elevated CO2-mitigation of high temperature stress associated with maintenance of
      positive carbon balance and carbohydrate accumulation in Kentucky bluegrass.
AB  - Elevated CO2 concentration may promote plant growth while high temperature is
      inhibitory for C3 plant species. The interactive effects of elevated CO2 and high
      temperatures on C3 perennial grass growth and carbon metabolism are not well
      documented. Kentucky bluegrass (Poa pratensis) plants were exposed to two CO2
      levels (400 and 800 MUmol mol-1) and five temperatures (15/12, 20/17, 25/22,
      30/27, 35/32 degrees C, day/night) in growth chambers. Increasing temperatures to
      25 degrees C and above inhibited leaf photosynthetic rate (Pn) and shoot and root
      growth, but increased leaf respiration rate (R), leading to a negative carbon
      balance and a decline in soluble sugar content under ambient CO2. Elevated CO2
      did not cause shift of optimal temperatures in Kentucky bluegrass, but promoted
      Pn, shoot and root growth under all levels of temperature (15, 20, 25, 30, and 35
      degrees C) and mitigated the adverse effects of severe high temperatures (30 and
      35 degrees C). Elevated CO2-mitigation of adverse effects of high temperatures on
      Kentucky bluegrass growth could be associated with the maintenance of a positive
      carbon balance and the accumulation of soluble sugars and total nonstructural
      carbohydrates through stimulation of Pn and suppression of R and respiratory
      organic acid metabolism. 

PMID- 24662767
TI  - NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis.
AB  - Cutaneous SCC (cSCC) is the most frequently occuring skin cancer with metastatic
      potential and can manifest rapidly as a common side effect in patients receiving
      systemic kinase inhibitors. Here, we use massively parallel exome and targeted
      level sequencing of 132 sporadic cSCCs and of 39 squamoproliferative lesions and
      cSCCs arising in patients receiving the BRAF inhibitor vemurafenib, as well as 10
      normal skin samples, to identify NOTCH1 mutation as an early event in squamous
      cell carcinogenesis. Bisected vemurafenib-induced lesions revealed surprising
      heterogeneity with different activating HRAS and NOTCH1 mutations identified in
      two halves of the same cSCC, suggesting polyclonal origin. Immunohistochemical
      analysis using an antibody specific to nuclear NOTCH1 correlates with mutation
      status in sporadic cSCCs, and regions of NOTCH1 loss or downregulation are
      frequently observed in normal-looking skin. Our data indicate that NOTCH1 acts as
      a gatekeeper in human cSCC. 

PMID- 24662770
TI  - Current aims and challenges associated with cervical cancer prevention.
AB  - This chapter will review the current modalities available to the clinician to
      screen for premalignant and malignant cervical lesions, which cast a broad net.
      The majority who test positive are not destined to suffer from or die from
      cervical cancer. Many who undergo screening and are triaged are young and
      subsequently face a number of aggressive and destructive therapies. This calls
      into question whether higher-risk patients should be managed more aggressively
      than an average-risk patient represented in the study population used to craft
      the guidelines. 

PMID- 24662769
TI  - Survey of infectious etiologies of bovine abortion during mid- to late gestation
      in dairy herds.
AB  - Bovine abortion of unknown infectious etiology still remains a major economic
      problem. Thus, we investigated whether Brucella spp., Listeria monocytogenes,
      Salmonella spp., Campylobacter spp. and Coxiella burnetii are associated with
      abortion and/or stillbirth in Tunisian dairy cattle. Using a pan-Chlamydiales
      PCR, we also investigated the role of Chlamydiaceae, Waddlia chondrophila,
      Parachlamydia acanthamoebae and other members of the Chlamydiales order in this
      setting. Veterinary samples taken from mid to late-term abortions from twenty
      dairy herds were tested. From a total of 150 abortion cases collected, infectious
      agents were detected by PCR in 73 (48.66%) cases, 13 (8.66%) of which represented
      co-infections with two infectious agents. Detected pathogens include Brucella spp
      (31.3%), Chlamydiaceae (4.66%), Waddlia chondrophila (8%), Parachlamydia
      acanthamoebae (5.33%), Listeria monocytogenes (4.66%) and Salmonella spp.
      (3.33%). In contrast, Campylobacter spp. and Coxiella burnetii DNA were not
      detected among the investigated veterinary samples. This demonstrates that
      different bacterial agents may cause bovine abortion in Tunisia. This is the
      first report suggesting the role of Parachlamydia acanthamoebae in bovine
      abortion in Africa. Further studies with a larger number of samples are necessary
      to confirm whether this emerging pathogen is directly linked to abortion in
      cattle. 

PMID- 24662771
TI  - Elective induction of labor symposium: nomenclature, research methodological
      issues, and outcomes.
AB  - Elective induction of labor is a controversial topic. An observed relationship
      between elective induction and primary cesarean delivery has been of particular
      concern, and has guided much of the research to date on both indicated and
      elective induction of labor. However, it is unclear whether elective induction of
      labor actually increases the risk of cesarean delivery. This chapter focuses on
      key method issues to consider in studies of elective induction of labor. We first
      identify methodological concerns with the existing literature and discuss each in
      turn. We then review existing evidence about the relationship between elective
      induction and cesarean delivery. 

PMID- 24662772
TI  - Outpatient approaches to elective induction of labor: past, present, and future.
AB  - Assessing the feasibility, acceptability and safety of outpatient labour
      induction. MEDLINE database was searched for "outpatient labor induction" from
      January 1, 1986 to February 28, 2013. Main outcomes of interest included
      hyperstimulation, cesarean births, Apgar scores <7 at 5 minutes, arterial-cord pH
      of <7.10, and neonatal morbidity/mortality. Overall cesarean rates vary
      significantly (2.6% to 42%). Hyperstimulation with CTG changes is rare. Neonatal
      admissions for diverse reasons are often not associated with outpatient induction
      agent. Overall, maternal satisfaction is high. Outpatient labor induction is
      feasible and important adverse events are rare. However, paucity of available
      data and heterogeneity of different studies make it difficult to quantify adverse
      events or identify a preferred induction method. 

PMID- 24662773
TI  - Circulating autoantibodies to oxidized low-density lipoprotein in patients with
      ascending aortic aneurysms: marker of oxidative stress involved in pathogenesis,
      epiphenomenon of endothelial dysfunction, or pure chance?

PMID- 24662774
TI  - Remote effects of hypothalamic lesions in the prefrontal cortex of
      craniopharygioma patients.
AB  - Albeit histologically low grade (WHO I(o)) brain tumors, craniopharyngiomas
      and/or their surgical removal frequently affect the hypothalamus, amongst other
      brain regions at risk. Due to rich hypothalamic connections with prefrontal and
      limbic regions, hypothalamic injury may adversely affect neural substrates of
      emotion processing and higher cognitive control, including memory and executive
      functions. The current study is the first to investigate the consequences of
      hypothalamic involvement on neural substrates of emotional and cognitive
      functioning. Ten patients with childhood craniopharyngioma and known hypothalamic
      involvement and fifteen age- and intelligence matched control subjects (median
      age: 17.8 and 17.3 yrs.) were studied with functional magnetic resonance imaging
      and an emotional face recognition task. During encoding, participants were asked
      to classify neutral and emotional faces. In a subsequent recognition phase,
      participants had to recognize these old faces within a set of new faces.
      Behavioral performance was comparable between patients and controls. Neural
      activity revealed, however, differential recruitment of fronto-limbic brain
      regions during recognition. Patients exhibited an abnormal pattern of task
      induced activation and deactivation in the anterior and posterior rostral medial
      prefrontal cortex and a higher functional coupling between anterior rostral
      medial prefrontal cortex and the thalamus. Additionally, we found a higher
      reactivity in the patients' amygdala to emotional relative to neutral faces when
      compared to healthy controls. Our data provide first evidence that hypothalamic
      damage impacts neural correlates of memory retrieval in medial prefrontal cortex,
      indicating a less efficient use of an area involved in executive control
      processes. We propose that the deactivation failure in the patients' anterior
      rostral medial prefrontal cortex is related to an increased coupling with the
      thalamus and reflects a reduced efficiency to flexibly adapt to task demands. 

PMID- 24662775
TI  - Application of three-dimensionally area-selective atomic layer deposition for
      selectively coating the vertical surfaces of standing nanopillars.
AB  - We describe a strategy for selectively coating the vertical surfaces of standing
      nanopillars using area-selective atomic layer deposition (ALD). Hydrophobic self
      assembled monolayers (SAMs) are utilised to selectively inhibit the coating of
      oxides on the modified horizontal regions to ensure that only the vertical
      surfaces of vertical standing nanorods are coated using ALD processes. This
      method makes it possible to fabricate vertical nanodevices using a simple process
      of depositing oxide layer on a vertical surface, and can also be applied to the
      area-selective surface passivation of other standing structures. 

PMID- 24662776
TI  - Mathematical modeling of HIV prevention measures including pre-exposure
      prophylaxis on HIV incidence in South Korea.
AB  - BACKGROUND: Multiple prevention measures have the possibility of impacting HIV
      incidence in South Korea, including early diagnosis, early treatment, and pre
      exposure prophylaxis (PrEP). We investigated how each of these interventions
      could impact the local HIV epidemic, especially among men who have sex with men
      (MSM), who have become the major risk group in South Korea. A mathematical model
      was used to estimate the effects of each these interventions on the HIV epidemic
      in South Korea over the next 40 years, as compared to the current situation.
      METHODS: We constructed a mathematical model of HIV infection among MSM in South
      Korea, dividing the MSM population into seven groups, and simulated the effects
      of early antiretroviral therapy (ART), early diagnosis, PrEP, and combination
      interventions on the incidence and prevalence of HIV infection, as compared to
      the current situation that would be expected without any new prevention measures.
      RESULTS: Overall, the model suggested that the most effective prevention measure
      would be PrEP. Even though PrEP effectiveness could be lessened by increased
      unsafe sex behavior, PrEP use was still more beneficial than the current
      situation. In the model, early diagnosis of HIV infection was also effectively
      decreased HIV incidence. However, early ART did not show considerable
      effectiveness. As expected, it would be most effective if all interventions
      (PrEP, early diagnosis and early treatment) were implemented together.
      CONCLUSIONS: This model suggests that PrEP and early diagnosis could be a very
      effective way to reduce HIV incidence in South Korea among MSM.

PMID- 24662777
TI  - Effects of lipid-lowering drugs on high-density lipoprotein subclasses in healthy
      men-a randomized trial.
AB  - CONTEXT AND OBJECTIVE: Investigating the effects of lipid-lowering drugs on HDL
      subclasses has shown ambiguous results. This study assessed the effects of
      ezetimibe, simvastatin, and their combination on HDL subclass distribution.
      DESIGN AND PARTICIPANTS: A single-center randomized parallel 3-group open-label
      study was performed in 72 healthy men free of cardiovascular disease with a
      baseline LDL-cholesterol of 111+/-30 mg/dl (2.9+/-0.8 mmol/l) and a baseline HDL
      cholesterol of 64+/-15 mg/dl (1.7+/-0.4 mmol/l). They were treated with ezetimibe
      (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24) or their combination (n =
      24) for 14 days. Blood was drawn before and after the treatment period. HDL
      subclasses were determined using polyacrylamide gel-tube electrophoresis.
      Multivariate regression models were used to determine the influence of treatment
      and covariates on changes in HDL subclass composition. RESULTS: Baseline HDL
      subclasses consisted of 33+/-10% large, 48+/-6% intermediate and 19+/-8% small
      HDL. After adjusting for baseline HDL subclass distribution, body mass index, LDL
      C and the ratio triglycerides/HDL-C, there was a significant increase in large
      HDL by about 3.9 percentage points (P<0.05) and a decrease in intermediate HDL by
      about 3.5 percentage points (P<0.01) in both simvastatin-containing treatment
      arms in comparison to ezetimibe. The parameters obtained after additional
      adjustment for the decrease in LDL-C indicated that about one third to one half
      of these effects could be explained by the extent of LDL-C-lowering. CONCLUSIONS:
      In healthy men, treatment with simvastatin leads to favorable effects on HDL
      subclass composition, which was not be observed with ezetimibe. Part of these
      differential effects may be due to the stronger LDL-C-lowering effects of
      simvastatin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00317993.

PMID- 24662778
TI  - Progression of myopic maculopathy after treatment of choroidal
      neovascularization.
AB  - PURPOSE: To evaluate the long-term progression of myopic maculopathy and
      functional outcome after treatment of myopic choroidal neovascularization (CNV)
      with photodynamic therapy (PDT) and/or intravitreal ranibizumab (IVR). METHODS:
      Retrospective study with a cross-sectional evaluation. Eyes were assigned to 4
      groups (PDT, IVR, PDT + IVR, dry myopic maculopathy) and evaluated with best
      corrected visual acuity, color fundus photography and spectral-domain optical
      coherence tomography. Chorioretinal atrophy progression was quantified. RESULTS:
      Fifty-four eyes were included with a mean follow-up of 80.6 +/- 28.0 months. The
      prevalence of diffuse, patchy and macular atrophy increased during the follow-up,
      in contrast with tessellated fundus, lacquer cracks and active CNV. Progression
      of macular atrophy was significant in the 3 treatment groups (p < 0.05) and
      predictive of visual acuity. It depended on age, degree of myopia and presence of
      staphyloma, but not on the type of treatment. CONCLUSIONS: The long-term
      functional outcome of eyes with myopic CNV is more dependent on the progression
      of macular atrophy, and not on the type of treatment.

PMID- 24662779
TI  - Refrigerated platelets for the treatment of acute bleeding: a review of the
      literature and reexamination of current standards.
AB  - This review is a synopsis of the decisions that shaped global policy on platelet
      (PLT) storage temperature and a focused appraisal of the literature on which
      those discussions were based. We hypothesize that choices were centered on
      optimization of preventive PLT transfusion strategies, possibly to the detriment
      of the therapeutic needs of acutely bleeding patients. Refrigerated PLTs are a
      better hemostatic product, and they are safer in that they are less prone to
      bacterial contamination. They were abandoned during the 1970s because of the
      belief that clinically effective PLTs should both be hemostatically functional
      and survive in circulation for several days as indicated for prophylactic
      transfusion; however, clinical practice may be changing. Data from two randomized
      controlled trials bring into question the concept that stable autologous stem
      cell transplant patients with hypoproliferative thrombocytopenia should continue
      to receive prophylactic transfusions. At the same time, new findings regarding
      the efficacy of cold PLTs and their potential role in treating acute bleeding
      have revived the debate regarding optimal PLT storage temperature. In summary, a
      "one-size-fits-all" strategy for PLT storage may not be adequate, and a
      reexamination of whether cold-stored PLTs should be offered as a widely available
      therapeutic product may be indicated. 

PMID- 24662780
TI  - Prehospital use of plasma: the blood bankers' perspective.
AB  - At the 2013 Traumatic Hemostasis and Oxygenation Research Network's Remote Damage
      Control Resuscitation symposium, a panel of senior blood bankers with both
      civilian and military background was invited to discuss their willingness and
      ability to supply prehospital plasma for resuscitation of massively bleeding
      casualties and to comment on the optimal preparations for such situations.
      Available evidence indicates that prehospital use of plasma may improve remote
      damage control resuscitation, although level I evidence is lacking. This practice
      is well established in several military services and is also being introduced in
      civilian settings. There are few, if any, clinical contraindications to the
      prehospital use of plasma, except for blood group incompatibility and the danger
      of transfusion-induced acute lung injury, which can be circumvented in various
      ways. However, the choice of plasma source, plasma preparation, and logistics
      including stock management require consideration. Staff training should include
      hemovigilance and traceability as well as recognition and management of eventual
      adverse effects. Prehospital use of plasma should occur within the framework of
      clinical algorithms and prospective clinical studies. Clinicians have an ethical
      responsibility to both patients and donors; therefore, the introduction of new
      clinical capabilities of transfusion must be safe, efficacious, and sustainable.
      The panel agreed that although these problems need further attention and
      scientific studies, now is the time for both military and civilian transfusion
      systems to prepare for prehospital use of plasma in massively bleeding
      casualties. 

PMID- 24662781
TI  - The future of observational research and randomized controlled trials in red
      blood cell transfusion medicine.
AB  - Red blood cell (RBC) transfusions are commonplace in the intensive care unit
      (ICU) with at least 30% of ICU patients receiving a RBC transfusion at some point
      during their ICU stay. However, which patients should be transfused and what
      transfusion trigger(s) should be used remains unclear. RBC transfusion can be
      associated with adverse effects, but anemia is also associated with worse
      outcomes. Observational studies and randomized controlled trials (RCTs) have been
      conducted to try and answer some of the questions surrounding blood transfusion
      in critically ill patients. The need for blood transfusion and the benefit/risk
      ratio vary according to individual patient characteristics, including age and
      comorbidities, so large-scale RCTs in heterogeneous groups of patients may not be
      the most appropriate tool to investigate these issues; smaller RCTs in carefully
      defined patient groups may provide more useful information. Rigorous statistical
      analysis of large, carefully conducted observational studies will also help
      enhance our evidence-base in this field. 

PMID- 24662782
TI  - Whole blood: the future of traumatic hemorrhagic shock resuscitation.
AB  - Toward the end of World War I and during World War II, whole-blood transfusions
      were the primary agent in the treatment of military traumatic hemorrhage.
      However, after World War II, the fractionation of whole blood into its components
      became widely accepted and replaced whole-blood transfusion to better accommodate
      specific blood deficiencies, logistics, and financial reasons. This transition
      occurred with very few clinical trials to determine which patient populations or
      scenarios would or would not benefit from the change. A smaller population of
      patients with trauma hemorrhage will require massive transfusion (>10 U packed
      red blood cells in 24 h) occurring in 3% to 5% of civilian and 10% of military
      traumas. Advocates for hemostatic resuscitation have turned toward a ratio
      balanced component therapy using packed red blood cells-fresh frozen plasma
      platelet concentration in a 1:1:1 ratio due to whole-blood limited availability.
      However, this "reconstituted" whole blood is associated with a significantly
      anemic, thrombocytopenic, and coagulopathic product compared with whole blood. In
      addition, several recent military studies suggest a survival advantage of early
      use of whole blood, but the safety concerns have limited is widespread civilian
      use. Based on extensive military experience as well as recent published
      literature, low-titer leukocyte reduced cold-store type O whole blood carries low
      adverse risks and maintains its hemostatic properties for up to 21 days. A
      prospective randomized trial comparing whole blood versus ratio balanced
      component therapy is proposed with rationale provided. 

PMID- 24662783
TI  - Implementation and execution of civilian remote damage control resuscitation
      programs.
AB  - Remote damage control resuscitation is a recently defined term used to describe
      techniques and strategies to provide hemostatic resuscitation to injured patients
      in the prehospital setting. In the civilian setting, unlike the typical military
      setting, patients who require treatment for hemorrhage come in all ages with all
      types of comorbidities and have bleeding that may be non-trauma related. Thus, in
      the austere setting, addressing the needs of the patient is no less challenging
      than in the military environment, albeit the caregivers are typically not putting
      their lives at risk to provide such care. Two organizations have pioneered remote
      damage control resuscitation in the civilian environment: Mayo Clinic and Royal
      Caribbean Cruises Ltd. The limitations in rural Minnesota and shipboard are
      daunting. Patients who have hemorrhage requiring transfusion are often hundreds
      of miles from hospitals able to provide damage control resuscitation. This
      article details the development and implementation of novel programs specifically
      designed to address the varied needs of patients in such circumstances. The Mayo
      Clinic program essentially takes a standard-of-care treatment algorithm, by which
      the patient would be treated in the emergency department or trauma bay, and
      projects that forward into the rural environment with specially trained
      prehospital personnel and special resources. Royal Caribbean Cruises Ltd has
      adapted a traditional military field practice of transfusing warm fresh whole
      blood, adding significant safety measures not yet reported on the battlefield
      (see within this Supplement the article entitled "Emergency Whole Blood Use in
      the Field: A Simplified Protocol for Collection and Transfusion"). The details of
      development, implementation, and preliminary results of these two civilian
      programs are described herein. 

PMID- 24662784
TI  - Association of plasma hormones, nutritional status, and stressful life events in
      anorexia nervosa patients.
AB  - OBJECTIVE: The aim of the current study was to analyze the relationships between
      plasma hormones, body weight parameters and stressful life events in anorexia
      nervosa (AN). MATERIAL AND METHODS: 72 females in the active phase of AN were
      evaluated. 52 healthy women constituted the control group. RIA kits were used to
      measure plasma hormone levels. RESULTS: The concentrations of leptin, insulin,
      IGF-1, triiodothyronine, LH, FSH, estradiol, and testosterone were significantly
      lower and those of cortisol and growth hormone significantly higher in the AN
      than the control group. No hormonal differences between restrictive and binge
      purging AN subtypes were found. Leptin, IGF-1, gonadotropins, and sex steroids
      correlated significantly negatively and growth hormone positively with total
      reduction of body weight or the degree of undernutrition. Associations were also
      found between lower insulin concentration and family violence, lower cortisol and
      psychiatric diseases in the family, higher testosterone and patient's alcohol or
      drug abuse. DISCUSSION: The changed activity of the somatotropin-somatomedin,
      gonadal, and corticotrophin axes corresponds to the clinical stage of AN. Plasma
      IGF-1 seems to be the most sensitive and useful independent hormonal marker of
      cachexia.

PMID- 24662785
TI  - [The effect of natural whey proteins on mechanisms of blood pressure regulation].
AB  - Whey is a rich natural source of peptides and amino acids. It has been reported
      in numerous studies that biological active peptides isolated from cow's milk whey
      may affect blood pressure regulation. Studies on animals and humans have shown
      that alpha-lactalbumin and beta-lactoglobulin obtained from enzymatically
      hydrolysed whey inhibit angiotensin converting enzyme (ACE), while lactorphins
      lower blood pressure by normalizing endothelial function or by opioid receptors
      dependent mechanism. Whey proteins or their bioactive fragments decrease total
      cholesterol, LDL fraction and triglycerides, thus reducing the risk factors of
      cardiovascular diseases. The aim of this review is to discuss the effects of whey
      proteins on the mechanisms of blood pressure regulation. 

PMID- 24662786
TI  - [Biochemical and clinical aspects of advanced oxidation protein products in
      kidney diseases and metabolic disturbances].
AB  - Intensified oxidative modification of proteins and increased concentration of
      advanced oxidation protein products (AOPPs) are confirmed by many experimental
      investigations in different pathological states, especially these with well-known
      participation of oxidative stress (OS) in etiopathogenesis but also these with
      not well recognized its role. Presented data indicate that AOPPs play a
      significant role in many disorders with chronic background, because of they
      reflect both intensification of OS and the degree of pathological changes
      connected with OS in these diseases. This review sets out the clinical and
      diagnostic aspects of AOPPs in these diseases such as: renal diseases with
      different etiology, cardiovascular diseases, as well as connected with metabolic
      disturbances - e.g. diabetes, atherosclerosis or metabolic syndrome. Moreover
      results of investigation about utility of AOPPs measurement, mainly in
      plasma/serum, in these diseases are presented. The review and evaluation of
      application of AOPPs as useful marker in diagnosis, prognosis and monitoring the
      course of these diseases were performed. This paper also describes the suggested
      mechanisms of their action which contribute to biochemical and clinic changes
      undergoing in the condition of increased OS. Diagnostic or prognostic utility of
      AOPPs are especially indicated in the course of diabetes and its complications
      (diabetic nephropahy) and cardiovascular diseases. 

PMID- 24662787
TI  - Influence of betulin and 28-O-propynoylbetulin on proliferation and apoptosis of
      human melanoma cells (G-361).
AB  - INTRODUCTION: Pentacyclic triterpenes are a group of compounds known to have
      anticancer activity. One of the best characterized triterpenes is betulin, which
      can be isolated from bark of birch trees and modified into new compounds with
      various interesting medical properties. Betulin is involved in activation of the
      caspase cascade and promotes cell death. The aim of the study was to investigate
      the effect of betulin and its acetylenic derivative, 28-O-propynoylbetulin, on
      proliferation and apoptosis in a human melanoma cell line. MATERIALS AND METHODS:
      The G-361 melanoma cell line was used. To evaluate growth arrest and caspase-3
      activity, cells were treated with betulin and its derivative at a wide range of
      concentrations from 0.1 to 10 MUg/mL. RESULTS: Betulin and 28-O-propynoylbetulin
      inhibited cell proliferation in a concentration-dependent manner. The cell cycle
      analysis revealed an increase of the sub-G1 cell fraction (representing dead
      cells) after incubation of cells with betulin and 28-O-propynoylbetulin. The
      observed cytotoxic effects were more pronounced for 28-O-propynoylbetulin.
      Activity of caspase-3 in 28-O-propynoylbetulin treated cells was nearly 2-fold
      greater compared to cells incubated with betulin. DISCUSSION: Our results show
      that betulin and 28-O-propynoylbetulin were effective in inhibition of cell
      growth and induction of apoptosis in a human melanoma cell line. The addition of
      the propynoyl group at the C-28 hydroxyl group of betulin led to a greater
      proapoptotic and antiproliferative effect in comparison to unmodified betulin.
      These observations suggest that the obtained derivative is a potent anti-melanoma
      agent.

PMID- 24662788
TI  - [Mitoxantrone - an anthraquinone antibiotic with antitumor activity applied for
      the treatment of multiple sclerosis].
AB  - Mitoxantrone is an antineoplastic agent approved for clinical use in the
      secondary progressive phase of multiple sclerosis (MS). Several scientific
      reports indicate that mitoxantrone acts through the induction of short-term cell
      lysis at high concentrations and long-term induction of programmed cell death at
      lower concentrations of antigen-presenting cells. In this paper, we present the
      potential cytotoxic effects of mitoxantrone on the cells of the immune system,
      whose activity is associated with their degenerative effects on axonal myelin
      sheaths. The article also evaluates the results from the hospital treatment of
      patients diagnosed with MS. The presented data indicate that, apart from the
      cytostatic properties, mitoxantrone also exhibits side effects of its clinical
      application. This drug has high cardiotoxicity, and is associated with decreased
      left ventricular ejection fraction and increased risk of congestive heart
      failure. Therefore researchers are currently looking for new substances that can
      reduce the toxic effects of mitoxantrone in healthy tissues, resulting in the
      generation of reactive oxygen species during its metabolism. 

PMID- 24662789
TI  - [Molecular fundamentals of drug interactions in the therapy of colorectal
      cancer].
AB  - Rapid advances in the field of chemotherapy have resulted in the introduction of
      numerous antineoplastic drugs into clinical practice, which increased the
      efficiency of patient management. Also the prevalent use of combination treatment
      based on drug action synergy contributed to the improved clinical effect
      associated with cytotoxic drug administration. It seems, however, obvious that
      the multidirectional pharmacotherapy in oncology requires a thorough knowledge of
      drugs' pharmaceutical behavior in order to maximize their collective action and
      prevent the occurrence of unintended drug interactions that could potentially
      impair treatment effectiveness. In fact, drug interactions constitute a serious
      problem for current oncology primarily resulting from a narrow therapeutic index
      specific for the majority of anticancer drugs. This, in turn, indicates that even
      slight deviations of their pharmacokinetics could cause significant clinical
      consequences, manifested by alteration of the toxicological profile or reduction
      of therapeutic efficiency. Hence, the investigation of molecular aspects
      underlying the mechanisms of various drug interactions seems to be essential for
      proper and safe patient management. The present article is devoted to the
      extensive subject of drug interactions occurring in the therapy of colorectal
      cancer. It presents the available literature data on both positive and negative
      effects of interactions and it discusses their mechanisms complying with their
      classification into pharmacokinetic and pharmacodynamic ones. 

PMID- 24662790
TI  - [Helicobacter pylori morphological forms and their potential role in the
      transmission of infection].
AB  - More than 50% of the world's population is infected with Helicobacter pylori (H.
      pylori) - a Gram negative bacterium, which persists in the human stomach and
      duodenum, causing gastric or duodenal ulcers and gastric cancer. The majority of
      H. pylori cells demonstrate rod-shape morphology occurring in two subtypes:
      spiral and S-shaped. Both are isolated from mucus layer biopsy specimens of the
      stomach or from short-term cultures. However, results obtained from electron
      microscopy revealed that H. pylori long-term cultures not only consist of
      classic, spiral shaped bacteria, but also contain alternative forms of coccoid
      cells. Further investigations showed that coccoid forms of H. pylori may be
      divided into two types: viable but non-culturable coccus (VBnC) and a
      degenerative form, coccoid stage which is probably the effect of bacterial cell
      death. Transformation from spiral to coccoid form is induced under stress
      conditions, such as the presence of antibiotics. But still there is no evidence
      for reversion from the coccoid state to the viable and infectious spiral form.
      Besides the planktonic form, H. pylori also forms homo-, and heterogenic
      biofilms, which may constitute a potential environmental reservoir of this
      bacterium. The antigenic repertoire and the immunomodulatory and infectious
      properties of different H. pylori forms differ greatly. The variation in those
      properties suggests that morphological forms of H. pylori are potentially
      involved in the transmission of the infection. This review presents recent
      findings on the variability, antigenicity and infectious properties of H. pylori
      morphological forms and their potential role in the transmission of the
      infection. 

PMID- 24662791
TI  - [The role of Toll-like receptors in the pathogenesis of allergic diseases - where
      is the truth?].
AB  - Toll-like receptors (TLRs) are pattern recognition receptors crucial for the
      innate and adaptive immune response to pathogen-associated molecular patterns
      (PAMPs). TLR stimulation via microbial products activates antigen-presenting
      cells, influences the function of T regulatory cells (Treg), determines the
      Th1/Th2 balance and Th17 cell differentiation, and controls cytokine production
      in mast cells and activation of eosinophils. The role of TLR receptors in
      pathogenesis of allergic diseases results from the biological function that they
      play in activation and regulation of the immune response. However, the exact role
      still remains a controversial area. Whereas numerous epidemiological studies
      mainly indicate a protective effect of microbial exposure, experiments show that
      innate immune stimulation via TLRs may be involved in both development of and
      protection against allergic diseases. Timing, dose, site and intensity of
      exposure to environmental factors and host genetic predisposition are clearly
      crucial to understanding the interaction between innate immune stimulation and
      allergy development.Furthermore, extensive clinical trials suggest that ligands
      for TLRs provide new therapeutic targets for protection against and treatment of
      asthma and allergic rhinitis. The aim of this review is to summarize the current
      knowledge about the role of TLRs in pathogenesis of allergic diseases. We will
      further discuss how we can reconcile inconsistencies in the results of existing
      studies and review information on the potential use of ligands for TLRs in
      allergy prevention and therapy. 

PMID- 24662792
TI  - [The role of genetic and environmental factors in the etiology of esophageal
      atresia and tracheo-esophageal fistula].
AB  - Esophageal atresia and tracheo-esophageal fistula are severe congenital
      malformations, whose etiology is still poorly understood. So far, numerous
      genetic and environmental factors that may contribute to the occurrence of these
      defects have been described and the literature is dominated by the view of their
      common involvement in the etiology and pathogenesis of congenital esophageal
      atresia. In this review the authors present current knowledge on the
      embryogenesis of the esophagus and trachea, discuss environmental risk factors,
      and also list and describe genetic alterations identified so far in patients with
      congenital esophageal atresia. 

PMID- 24662793
TI  - [Metformin as a key to alternative activation of microglia?].
AB  - The results of recent studies suggest that metformin, in addition to its
      antihyperglycemic efficacy, may also attenuate neuroinflammation and directly act
      on the central nervous system. However, the molecular mechanisms by which
      metformin exerts its anti-inflammatory effects in the brain remain largely
      unknown. Adenosine-monophosphate-activated protein kinase (AMPK) activation is
      the most well-known mechanism of metformin action. However, some of the
      biological responses to metformin (e.g. the release of cytokines and the
      expression of arginase I or PGC-1alpha) are not limited to AMPK activation but
      also are mediated by AMPK-independent mechanisms. This article reviews current
      evidence supporting the hypothesis that the shift of microglia toward alternative
      activation may underlie the beneficial effects of metformin observed in animal
      models of neurological disorders. 

PMID- 24662794
TI  - [Molecular mechanisms regulating metastasis of cancer cells with special emphasis
      on rhabdomyosarcoma].
AB  - Rhabdomyosarcoma (RMS) is a malignant tumor of soft tissue derived from embryonic
      mesenchymal and/or neuroectodermal tissues. It is most often associated with
      other genetic syndromes such as Li-Fraumeni or Bechwith-Wiedeman. RMS cells show
      morphological similarities to striated muscle and the presence of specific
      markers of muscle tissue. At the histological level, it is divided into two
      subtypes (alveolar RMS - ARMS and embryonal RMS - ERMS), which differ in their
      genetic background, and prognosis. In recent years there has been significant
      progress in understanding the mechanisms that regulate RMS cell growth and
      metastasis. Recently, a number of several chemokines, cytokines or growth factors
      and their receptors were identified involved in RMS pathogenesis as well as
      animal models of this tumor have been developed. This knowledge is of great
      importance in the development of potential therapeutic strategies not only in
      RMS, but also other types of cancer. This paper will discuss the theories of the
      origin of this rare tumor and the molecular mechanisms involved in its growth and
      metastasis. The processes and mechanisms described herein, such as chemotaxis,
      adhesion, proliferation, intracellular signal transduction, seem to universal for
      number of cancer types. 

PMID- 24662795
TI  - Bacteria, viruses, and hypothalamic inflammation: potential new players in
      obesity.
AB  - Being overweight and obese has become an increasingly serious clinical and
      socioeconomic problem worldwide. The rapidly rising prevalence of obesity has
      prompted studies on modifiable, causative factors and novel treatment options for
      this disorder. Recent evidence indicates that excessive weight gain that leads to
      being overweight and obese may result from alterations in gut microflora. Studies
      in humans and animals demonstrated that the composition of gut microbiota may
      differ in lean and obese subjects, suggesting that these differences result in
      the increased efficiency of caloric extraction from food, enhanced lipogenesis,
      and impaired central and peripheral regulation of energy balance. Other studies
      revealed an excessive increase in body weight in a significant percentage of
      people infected with human adenoviruses SMAM-1 and Ad-36. Dysregulation of
      adipocyte function by viruses appears to be the most likely cause of excessive
      fat accumulation in these individuals. Studies on the pathomechanisms related to
      the pathogenesis of obesity indicated that a high-fat diet triggers the
      inflammatory response in the hypothalamus, an event that promotes weight gain and
      further defends elevated body weight through the initiation of central leptin and
      insulin resistance and impairment of regenerative capacity of hypothalamic
      neurons. Exposure to a high-calorie diet appears to predispose individuals to
      obesity not only because of excessive caloric intake but also because of the
      induction of microbiota- and central inflammatory response-dependent changes that
      lead to a dysregulation of energy balance. 

PMID- 24662796
TI  - [The biological significance of oxidative modifications of cysteine residues in
      proteins illustrated with the example of glyceraldehyde-3-phosphate
      dehydrogenase].
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key redox-sensitive
      protein, the activity of which is largely affected by oxidative modifications at
      its highly reactive cysteine residue in the active site of the enzyme (Cys-152).
      These modifications occur as a result of S-thiolation, S-nitrosylation or
      disulfide bonds that lead to aggregate formation. The oxidative changes not only
      affect the glycolytic function but also stimulate the participation of GAPDH in
      numerous cellular processes. In this review we describe how thiol modification of
      Cys-152 in GAPDH re-routes metabolic pathways in the cell and converts a
      metabolic enzyme into a pro-apoptotic factor. Especially interesting issue is the
      participation of GAPDH in the regulation of expression of endothelin 1 and
      nitrosylation of nuclear proteins. In the last section we describe involvement of
      GAPDH in the processes associated with neurodegenerative diseases. 

PMID- 24662797
TI  - [Genetic and immunologic determinants of intravesical BCG therapy in non-muscle
      invasive urothelial bladder cancer].
AB  - Bladder cancer (BCA) is one of the most common cancers. In 2010 in Poland, 6296
      people developed bladder cancer and 3110 people died of it. Immunotherapy with
      BCG (Bacillus Calmette-Guerin) is by far the most effective adjuvant therapy.
      Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify
      for BCG immunotherapy. BCG immunotherapy comprises series of bladder
      instillations, containing attenuated strain of Mycobacterium bovis. The
      effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year
      survival without recurrence of the tumor. The treatment leads to a reduction of
      the residual tumor mass, but also to the delay and/or prevention of relapse,
      disease progression and ultimately death. Cytokines, as key mediators of immune
      response, play an important role in the pathogenesis of bladder cancer, which
      occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes
      an intensive immunological response by the increase of cytokine production.
      Genetic variants determine inter-individual differences in the incidence of this
      cancer, as well as the response to the therapy. This is evidenced by the presence
      of differences in genetic variants of cytokines correlated with the varied risk
      of bladder cancer incidence. It is believed that concentrations of particular
      cytokines in urine after installation of BCG may indicate response to the
      therapy. Increased levels of Th1 cytokines - IFN-gamma, IL-2 and TNF-alpha are
      correlated with longer survival time without recurrence, whereas high levels of
      Th2 cytokines such as IL-10, predict unsuccessful BCG therapy. 

PMID- 24662798
TI  - [SMAD family proteins: the current knowledge on their expression and potential
      role in neoplastic diseases].
AB  - Transforming growth factor beta (TGF-beta) plays a crucial role and takes part in
      many processes in the human body both in physiology and pathology. This cytokine
      is involved in angiogenesis, regulates apoptosis and stimulates divisions of
      cells, such as hepatocytes, lymphocytes or hematopoietic cells. SMAD proteins
      family is a unique group of particles responsible for transducting the signal
      induced by TGF-beta into the nucleus. This molecules, after receiving a signal
      from activated TGF-beta, act on transcription factors in the nucleus, leading
      directly to the expression of the corresponding genes. According to current
      knowledge, disturbances in the functioning of SMAD proteins are present in a
      number of diseases. The reduced expression was observed, for example in
      cardiovascular diseases such as primary pulmonary hypertension or myocardial
      infarction, autoimmune diseases for instance systemic lupus erythematosus and
      multiple sclerosis, Alzheimer's disease or osteoporosis. The latest clinical data
      showed the presence of mutations in SMAD proteins in cancerogenesis. Mutation of
      SMAD-4 protein can be detected in half of the patients with pancreatic cancer,
      20% of patients with colorectal cancer and 10% of patients with lung cancer.
      However, mutation in SMAD-2 protein was observed in 7% of both patients with
      colorectal cancer and lung cancer. On the basis of numerous works, SMAD protein
      expression would be valuable prognostic factor in some of neoplastic diseases. 

PMID- 24662799
TI  - Muscarinic acetylcholine receptor X-ray structures: potential implications for
      drug development.
AB  - Muscarinic acetylcholine receptor antagonists are widely used as bronchodilating
      drugs in pulmonary medicine. The therapeutic efficacy of these agents depends on
      the blockade of M3 muscarinic receptors expressed on airway smooth muscle cells.
      All muscarinic antagonists currently used as bronchodilating agents show high
      affinity for all five muscarinic receptor subtypes, thus increasing the
      likelihood of unwanted side effects. Recent X-ray crystallographic studies have
      provided detailed structural information about the nature of the orthosteric
      muscarinic binding site (the conventional acetylcholine binding site) and an
      'outer' receptor cavity that can bind allosteric (non-orthosteric) drugs. These
      new findings should guide the development of selective M3 receptor blockers that
      have little or no effect on other muscarinic receptor subtypes. 

PMID- 24662800
TI  - Evolution of separate predation- and defence-evoked venoms in carnivorous cone
      snails.
AB  - Venomous animals are thought to inject the same combination of toxins for both
      predation and defence, presumably exploiting conserved target pharmacology across
      prey and predators. Remarkably, cone snails can rapidly switch between distinct
      venoms in response to predatory or defensive stimuli. Here, we show that the
      defence-evoked venom of Conus geographus contains high levels of paralytic toxins
      that potently block neuromuscular receptors, consistent with its lethal effects
      on humans. In contrast, C. geographus predation-evoked venom contains prey
      specific toxins mostly inactive at human targets. Predation- and defence-evoked
      venoms originate from the distal and proximal regions of the venom duct,
      respectively, explaining how different stimuli can generate two distinct venoms.
      A specialized defensive envenomation strategy is widely evolved across worm,
      mollusk and fish-hunting cone snails. We propose that defensive toxins,
      originally evolved in ancestral worm-hunting cone snails to protect against
      cephalopod and fish predation, have been repurposed in predatory venoms to
      facilitate diversification to fish and mollusk diets. 

PMID- 24662802
TI  - Residential area, birth order, and dietary habit may influence TSLP levels in
      colostrum: comparative study between Japan and Nepal.

PMID- 24662801
TI  - Intensified chemo-immunotherapy with or without stem cell transplantation in
      newly diagnosed patients with peripheral T-cell lymphoma.
AB  - Peripheral T-cell lymphomas (PTCLs) receiving conventional treatment have a poor
      clinical outcome. We conducted a phase II study to evaluate the feasibility and
      efficacy of chemo-immunotherapy in young (?60 years old, Clin A study) and
      elderly (>60 and < or =75 years old, Clin B study) patients with newly diagnosed
      PTCL. Clin A patients (n=61) received two courses of CHOP (cyclophosphamide,
      adriamycin, vincristine, prednisone)-21 with alemtuzumab (AL, 30 mg) followed by
      two courses of high-dose chemotherapy. On the basis of donor availability,
      patients in response received allogeneic (allo) or autologous (auto) stem cell
      transplantation (SCT). Clin B patients (n=25) received six courses of CHOP-21 and
      AL (10 mg). Clin A responding patients were 38 of 61 (62%) and received alloSCT
      (n=23) or autoSCT (n=14); one complete remission (CR) patient was not
      transplanted. At a median follow-up of 40 months, the 4-year overall survival
      (OS), progression-free survival (PFS) and disease-free survival (DFS) rates were
      49, 44 and 65%, respectively. In Clin B study, the response rate was 72%. At a
      median follow-up of 48 months, the 4-year OS, PFS and DFS rates were 31, 26 and
      44%, respectively. In conclusion, front-line alloSCT or autoSCT is effective in
      prolonging DFS in young patients; AL in elderly improved response with no
      survival benefit.

PMID- 24662803
TI  - Is there a need for repetition of skin test in childhood allergic diseases?
      Repetition of skin test and allergic diseases.
AB  - BACKGROUND: Skin prick tests are widely used to determine sensitivity in allergic
      diseases. There is limited information about the natural history of skin
      sensitization tests and factors that affect them. It was aimed to determine the
      changes in skin test results and the factors affecting the reactivity of skin
      tests after a period of approximately four years in children with allergic
      disease. METHODS: SPT of 170 patients among 2485 children with asthma and/or
      allergic rhinitis and/or atopic dermatitis, who underwent SPT between 2005 and
      2007, were repeated after an interval of at least 3 years. RESULTS: The mean age
      was 10.7 +/- 3.1 (5-18) years and 70% of the patients were male. In total 66
      (39.0% of the study population) had a different skin tests result in follow-up.
      Alterations: loss of sensitivity in 18 (11%) patients, the formation of a new
      sensitivity in 37 (22%) patients, and 11 (6%) both gained and lost sensitization.
      The presence of atopy in the family, the presence of allergic rhinitis and IgE
      elevation significantly predicted the incidence of new sensitization. The
      presence of sensitization to multiple allergens significantly predicted the
      incidence of loss of sensitization. CONCLUSIONS: It is found that there was an
      alteration of sensitization in 4/10 children at the end of the average 4-year
      period. The presence of family atopy, the presence of allergic rhinitis and serum
      total IgE elevation were risk factors for the development of new sensitization.
      On the other hand sensitization to multiple allergens was risk factors for the
      loss of sensitization.

PMID- 24662804
TI  - Agreement between the skin prick test and specific serum IgE for egg white and
      cow's milk allergens in young infant with atopic dermatitis.
AB  - BACKGROUND: The skin prick test (SPT) for detecting atopic sensitization is not
      preferred in young infants with atopic dermatitis (AD) because of concerns about
      poor skin reactivity. This study aimed to evaluate whether the results of SPT
      agreed well with those of specific serum immunoglobulin E (sIgE) antibody test in
      young infants with AD. METHODS: This study included 2,077 eligible infants (age,
      <12 months) with AD who were tested by either SPT or sIgE between 2007 and 2011.
      Among them, 199 infants tested for egg white (EW) and 192 infants tested for
      cow's milk (CM), by both SPT and sIgE on the same day were identified and
      reviewed retrospectively. Kappa statistics and tests for equal kappa statistics
      were used to evaluate the agreement between the SPT and sIgE. RESULTS: The mean
      wheal diameter and the allergen-to-histamine ratio of SPT showed substantial
      agreement with those of sIgE for EW (kappa = 0.62, 0.69) and CM (kappa = 0.34,
      0.47). The agreement for EW was significantly higher <6-month-old than in >=6
      month-old infants (kappa = 0.79 vs. 0.54, P = 0.02), and that for CM was similar
      (P = 0.60). The mean wheal diameters for EW and CM were evenly distributed, and
      did not show increasing trends regardless of age in months (Ptrend = 0.13 and
      0.06, respectively). CONCLUSIONS: The results of SPT agreed well with those of
      sIgE. This finding provides a rationale for using SPT, and suggests that SPT can
      be used along with sIgE to detect food sensitization in young infants with AD.

PMID- 24662805
TI  - Epicutaneous administration of papain induces IgE and IgG responses in a cysteine
      protease activity-dependent manner.
AB  - BACKGROUND: Epicutaneous sensitization to allergens is important in the
      pathogenesis of not only skin inflammation such as atopic dermatitis but also
      "atopic march" in allergic diseases such as asthma and food allergies. We here
      examined antibody production and skin barrier dysfunction in mice epicutaneously
      administered papain, a plant-derived occupational allergen belonging to the same
      family of cysteine proteases as mite major group 1 allergens. METHODS: Papain and
      Staphylococcus aureus V8 protease were patched on the backs of hairless mice.
      Transepidermal water loss was measured to evaluate the skin barrier dysfunction
      caused by the proteases. Papain or that treated with an irreversible inhibitor
      specific to cysteine proteases, E64, was painted onto the ear lobes of mice of an
      inbred strain C57BL/6. Serum total IgE levels and papain-specific IgE and IgG
      antibodies were measured by ELISA. RESULTS: Papain and V8 protease patched on the
      backs of hairless mice caused skin barrier dysfunction and increased serum total
      IgE levels, and papain induced the production of papain-specific IgG1, IgG2a, and
      IgG2b. Papain painted onto the ear lobes of C57BL/6 mice induced papain-specific
      IgE, IgG1, IgG2c, and IgG2b, whereas papain treated with E64 did not. IgG1 was
      the most significantly induced papain-specific IgG subclass among those measured.
      CONCLUSIONS: We demonstrated that the epicutaneous administration of protease not
      only disrupted skin barrier function, but also induced IgE and IgG responses in a
      manner dependent on its protease activity. These results suggest that protease
      activity contained in environmental sources contributes to sensitization through
      an epicutaneous route.

PMID- 24662806
TI  - Periostin in allergic inflammation.
AB  - Periostin, an extracellular matrix protein belonging to the fasciclin family, has
      been shown to play a critical role in the process of remodeling during
      tissue/organ development or repair. Periostin functions as a matricellular
      protein in cell activation by binding to their receptors on cell surface, thereby
      exerting its biological activities. After we found that periostin is a downstream
      molecule of interleukin (IL)-4 and IL-13, signature cytokines of type 2 immune
      responses, we showed that periostin is a component of subepithelial fibrosis in
      bronchial asthma, the first formal proof that periostin is involved in allergic
      inflammation. Subsequently, a great deal of evidence has accumulated
      demonstrating the significance of periostin in allergic inflammation. It is of
      note that in skin tissues, periostin is critical for amplification and
      persistence of allergic inflammation by communicating between fibroblasts and
      keratinocytes. Furthermore, periostin has been applied to development of novel
      diagnostics or therapeutic agents for allergic diseases. Serum periostin can
      reflect local production of periostin in inflamed lesions induced by Th2-type
      immune responses and also can predict the efficacy of Th2 antagonists against
      bronchial asthma. Blocking the interaction between periostin and its receptor,
      alphav integrin, or down-regulating the periostin expression shows improvement of
      periostin-induced inflammation in mouse models or in in vitro systems. It is
      hoped that diagnostics or therapeutic agents targeting periostin will be of
      practical use in the near future. 

PMID- 24662807
TI  - Inhibition of c-Kit signaling is associated with reduced heat and cold pain
      sensitivity in humans.
AB  - The tyrosine kinase receptor c-Kit is critically involved in the modulation of
      nociceptive sensitivity in mice. Ablation of the c-Kit gene results in
      hyposensitivity to thermal pain, whereas activation of c-Kit produces
      hypersensitivity to noxious heat, without altering sensitivity to innocuous
      mechanical stimuli. In this study, we investigated the role of c-Kit signaling in
      human pain perception. We hypothesized that subjects treated with Imatinib or
      Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1,
      PDFGFRalpha, and PDFGFRbeta, that are used to treat chronic myeloid leukemia
      (CML), would experience changes in thermal pain sensitivity. We examined 31
      asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib
      treatment and compared them to 39 age- and sex-matched healthy controls (12 male
      and 27 female). We used cutaneous heat and cold stimulation to test normal and
      noxious thermal sensitivity, and a grating orientation task to assess tactile
      acuity. Thermal pain thresholds were significantly increased in the
      Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile
      thresholds were unchanged compared to those in the control group. In conclusion,
      our findings suggest that the biological effects of c-Kit inhibition are
      comparable in mice and humans in that c-Kit activity is required to regulate
      thermal pain sensitivity but does not affect innocuous thermal and mechanical
      sensation. The effect on experimental heat pain observed in our study is
      comparable to those of several common analgesics; thus modulation of the c-Kit
      pathway can be used to specifically modulate noxious heat and cold sensitivity in
      humans. 

PMID- 24662809
TI  - Comparison of the test-retest reliability of the balance computerized adaptive
      test and a computerized posturography instrument in patients with stroke.
AB  - OBJECTIVE: To compare the test-retest reliabilities of the scores of the Balance
      Computerized Adaptive Test (CAT) and the Biodex Balance System in patients with
      stroke. DESIGN: A repeated-measures design (at a 1-wk interval) was used to
      examine the test-retest reliabilities of the scores of the Balance CAT and the
      Biodex Balance System. SETTING: One rehabilitation unit in a local hospital.
      PARTICIPANTS: Patients (N=50) with stroke for more than 6 months and undergoing
      outpatient rehabilitation completed the Balance CAT and the eyes open (EO)/closed
      (EC) tests, but only 17 patients finished the Limit of Stability (LOS) test
      because they were unable to reach all the targets. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: The Balance CAT and 2 computerized tests of the Biodex
      Balance System, namely the EO/EC test and the LOS, were used to evaluate balance
      function. RESULTS: The test-retest reliabilities of the scores of the Balance CAT
      (Pearson r=.92, minimal detectable change [MDC] percent=12.8%) was excellent.
      Those of the EO/EC and LOS tests were poor to good (Pearson r=.56-.85, MDC%=50.8%
      126.9%). CONCLUSIONS: The test-retest reliabilities of the scores of the Balance
      CAT were sufficient for assessing balance function in patients with stroke.
      Moreover, the test-retest reliabilities of the scores of the Balance CAT, one of
      the functional balance measures, were superior to those of the Biodex Balance
      System, 1 type of computerized posturography instrument. Therefore, the Balance
      CAT may be a more reliable measure for clinicians and researchers to use in
      assessing the balance function of patients with stroke for more than 6 months.

PMID- 24662810
TI  - Is extracorporeal shock wave therapy clinical efficacy for relief of chronic,
      recalcitrant plantar fasciitis? A systematic review and meta-analysis of
      randomized placebo or active-treatment controlled trials.
AB  - OBJECTIVE: To assess the efficacy of extracorporeal shockwave therapy (ESWT) and
      provide clinicians with an evidence base for their clinical decision making. DATA
      SOURCES: PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials,
      and Evidence-Based Medicine Reviews. STUDY SELECTION: All randomized or quasi
      randomized controlled trials of ESWT for chronic recalcitrant plantar fasciitis
      were searched. Searching identified 108 potentially relevant articles; of these,
      7 studies with 550 participants met inclusion criteria. DATA EXTRACTION: Number
      of patients, population, body mass index, duration of symptoms, adverse effects,
      blinding method, and details of shockwave therapy were extracted. DATA SYNTHESIS:
      For intervention success rate, ESWT of low intensity was more effective than
      control treatment of low intensity. For pain relief, the pooled data showed a
      significant difference between the ESWT and control groups. For function, only
      low-intensity ESWT was significantly superior over the control treatment.
      CONCLUSIONS: The efficacy of low-intensity ESWT is worthy of recognition. The
      short-term pain relief and functional outcomes of this treatment are
      satisfactory. However, owing to the lack of a long-term follow-up, its long-term
      efficacy remains unknown.

PMID- 24662811
TI  - Gravity-supported exercise with computer gaming improves arm function in chronic
      stroke.
AB  - OBJECTIVE: To investigate the effect of 4 to 6 weeks of exergaming with a
      computer mouse embedded within an arm skate on upper limb function in survivors
      of chronic stroke. DESIGN: Intervention study with a 4-week postintervention
      follow-up. SETTING: In home. PARTICIPANTS: Survivors (N=13) of chronic (>=6 mo)
      stroke with hemiparesis of the upper limb with stable baseline Fugl-Meyer
      assessment scores received the intervention. One participant withdrew, and 2
      participants were not reassessed at the 4-week follow-up. No participants
      withdrew as a result of adverse effects. INTERVENTION: Four to 6 weeks of
      exergaming using the arm skate where participants received either 9 (n=5) or 16
      (n=7) hours of game play. MAIN OUTCOME MEASURE: Upper limb component of the Fugl
      Meyer assessment. RESULTS: There was an average increase in the Fugl-Meyer upper
      limb assessment score from the beginning to end of the intervention of 4.9
      points. At the end of the 4-week period after the intervention, the increase was
      4.4 points. CONCLUSIONS: A 4- to 6-week intervention using the arm skate
      significantly improved arm function in survivors of chronic stroke by an average
      of 4.9 Fugl-Meyer upper limb assessment points. This research shows that a larger
      scale randomized trial of this device is warranted and highlights the potential
      value of using virtual reality technology (eg, computer games) in a
      rehabilitation setting.

PMID- 24662812
TI  - Prevalence and predictors of adolescent idiopathic scoliosis in adolescent ballet
      dancers.
AB  - OBJECTIVE: To determine any differences between the prevalence of adolescent
      idiopathic scoliosis in ballet dancers who are girls compared with age-matched
      nondancers, and to establish if any relations exist between the presence of
      scoliosis and generalized joint hypermobility, age of menarche, body mass index
      (BMI), and the number of hours of dance training per week. DESIGN: Cross
      sectional, matched pair study. SETTING: Dance school. PARTICIPANTS: Dancers
      (n=30) between the ages of 9 and 16 years were recruited from a certified dance
      school in Western Australia; each dancer provided a consenting age-matched
      nondancer (n=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Measurements were taken for angle of trunk rotation using a scoliometer (presence
      of scoliosis) and for height and weight to produce generalized joint
      hypermobility using Beighton criteria and an age-adjusted BMI, respectively. A
      subjective questionnaire regarding age of menarche and participation in dance and
      other sports was completed. RESULTS: Thirty percent of dancers tested positive
      for scoliosis compared with 3% of nondancers. Odds ratio calculations suggest
      that dancers were 12.4 times more likely to have scoliosis than nondancers of the
      same age. There was a higher rate of hypermobility in the dancer group (70%)
      compared with the nondancers (3%); however, there were no statistically
      significant relations between scoliosis and hypermobility, age of menarche, BMI,
      or hours of dance per week. CONCLUSIONS: Adolescent dancers, similar to adult
      dancers, are at significantly higher risk of developing scoliosis than nondancers
      of the same age. Vigilant screening and improved education of dance teachers and
      parents of dance students may be beneficial in earlier detection and,
      consequently, reducing the risk of requiring surgical intervention.

PMID- 24662813
TI  - Derivation of a clinical decision guide in the diagnosis of cervical facet joint
      pain.
AB  - OBJECTIVE: To derive a clinical decision guide (CDG) to identify patients best
      suited for cervical diagnostic facet joint blocks. DESIGN: Prospective cohort
      study. SETTING: Pain management center. PARTICIPANTS: Consecutive patients with
      neck pain (N=125) referred to an interventional pain management center were
      approached to participate. INTERVENTIONS: Subjects underwent a standardized
      testing protocol, performed by a physiotherapist, prior to receiving diagnostic
      facet joint blocks. All subjects received the reference standard diagnostic facet
      joint block protocol, namely controlled medial branch blocks (MBBs). The
      physicians performing the MBBs were blinded to the local anesthetic used and
      findings of the clinical tests. MAIN OUTCOME MEASURES: Multivariate regression
      analyses were performed in the derivation of the CDGs. Sensitivity, specificity,
      positive and negative likelihood ratios, and 95% confidence intervals (CIs) were
      calculated for the index tests and CDGs. RESULTS: A CDG involving the findings of
      the manual spinal examination (MSE), palpation for segmental tenderness (PST),
      and extension-rotation (ER) test demonstrated a specificity of 84% (95% CI, 77
      90) and a positive likelihood ratio of 4.94 (95% CI, 2.8-8.2). Sensitivity of the
      PST and MSE were 94% (95% CI, 90-98) and 92% (95% CI, 88-97), respectively.
      Negative findings on the PST were associated with a negative likelihood ratio of
      .08 (95% CI, .03-.24). CONCLUSIONS: MSE, PST, and ER may be useful tests in
      identifying patients suitable for diagnostic facet joint blocks. Further research
      is needed to validate the CDGs prior to their routine use in clinical practice.

PMID- 24662814
TI  - Ahnak functions as a tumor suppressor via modulation of TGFbeta/Smad signaling
      pathway.
AB  - We provide detailed mechanisms of Ahnak-mediated potentiation of transforming
      growth factor beta (TGFbeta) signaling, which leads to a negative regulation of
      cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that
      Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFbeta
      induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak
      resulted in growth retardation and cell cycle arrest through downregulation of c
      Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model
      expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(
      /-)), which showed significantly progressed hyperplasia of mammary glands
      compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast
      cancer tissues and showed that the expression of Ahnak in cancer tissues is lower
      than that in control tissues by 50%. Taken together, these data indicate that
      Ahnak mediates a negative regulation of cell growth and acts as novel tumor
      suppressor through potentiation of TGFbeta signaling. 

PMID- 24662815
TI  - The kinetics of ER fusion protein activation in vivo.
AB  - Reversibly switchable proteins are powerful tools with which to explore protein
      function in vitro and in vivo. For example, the activity of many proteins fused
      to the hormone-binding domain of the modified oestrogen receptor (ER(TAM)) can be
      regulated by provision or removal of 4-hydroxytamoxifen (4-OHT). Despite the
      widespread use of ER(TAM) fusions in vivo, inadequate data are available as to
      the most efficacious routes for systemic tamoxifen delivery. In this study, we
      have used two well-characterized ER(TAM) fusion proteins, both reversibly
      activated by 4-OHT, to compare the effectiveness and kinetics of 4-OHT delivery
      in mice in vivo by either tamoxifen in food or by intraperitoneal injection. Our
      data indicate that dietary tamoxifen offers an effective, facile and ethically
      preferable means for long-term activation of ER(TAM) fusion proteins in vivo. 

PMID- 24662816
TI  - AIP inactivation leads to pituitary tumorigenesis through defective Galphai-cAMP
      signaling.
AB  - The aryl hydrocarbon receptor interacting protein (AIP) is a tumor-suppressor
      gene underlying the pituitary adenoma predisposition. Thus far, the exact
      molecular mechanisms by which inactivated AIP exerts its tumor-promoting action
      have been unclear. To better understand the role of AIP in pituitary
      tumorigenesis, we performed gene expression microarray analysis to examine
      changes between Aip wild-type and knockout mouse embryonic fibroblast (MEF) cell
      lines. Transcriptional analyses implied that Aip deficiency causes a dysfunction
      in cyclic adenosine monophosphate (cAMP) signaling, as well as impairments in
      signaling cascades associated with developmental and immune-inflammatory
      responses. In vitro experiments showed that AIP deficiency increases
      intracellular cAMP concentrations in both MEF and murine pituitary adenoma cell
      lines. Based on knockdown of various G protein alpha subunits, we concluded that
      AIP deficiency leads to elevated cAMP concentrations through defective Galphai-2
      and Galphai-3 proteins that normally inhibit cAMP synthesis. Furthermore,
      immunostaining of Galphai-2 revealed that AIP deficiency is associated with a
      clear reduction in Galphai-2 protein expression levels in human and mouse growth
      hormone (GH)-secreting pituitary adenomas, thus indicating defective Galphai
      signaling in these tumors. By contrast, all prolactin-secreting tumors showed
      prominent Galphai-2 protein levels, irrespective of Aip mutation status. We
      additionally observed reduced expression of phosphorylated extracellular signal
      regulated kinases 1/2 and cAMP response element-binding protein levels in mouse
      and human AIP-deficient somatotropinomas. This study implies for the first time
      that a failure to inhibit cAMP synthesis through dysfunctional Galphai signaling
      underlies the development of GH-secreting pituitary adenomas in AIP mutation
      carriers. 

PMID- 24662817
TI  - Integrated genomic and functional analyses reveal glyoxalase I as a novel
      metabolic oncogene in human gastric cancer.
AB  - Chromosomal abnormalities are good guideposts when hunting for cancer-related
      genes. We analyzed copy number alterations of 163 primary gastric cancers using
      array-based comparative genomic hybridization and simultaneously performed a
      genome-wide integrated analysis of copy number and gene expression using
      microarray data for 58 tumors. We showed that chromosome 6p21 amplification
      frequently occurred secondary to ERBB2 amplification, was associated with poorer
      prognosis and caused overexpression of half of the genes mapped. A comprehensive
      small interfering RNA knockdown of 58 genes overexpressed in tumors identified 32
      genes that reduced gastric cancer cell growth. Enforced expression of 16 of these
      genes promoted cell growth in vitro, and six genes showing more than two-fold
      activity conferred tumor-forming ability in vivo. Among these six candidates,
      GLO1, encoding a detoxifying enzyme glyoxalase I (GLO1), exhibited the strongest
      tumor-forming activity. Coexpression of other genes with GLO1 enhanced growth
      stimulating activity. A GLO1 inhibitor, S-p-bromobenzyl glutathione cyclopentyl
      diester, inhibited the growth of two-thirds of 24 gastric cancer cell lines
      examined. The efficacy was found to be associated with the mRNA expression ratio
      of GLO1 to GLO2, encoding glyoxalase II (GLO2), another constituent of the
      glyoxalase system. GLO1 downregulation affected cell growth through inactivating
      central carbon metabolism and reduced the transcriptional activities of nuclear
      factor kappa B and activator protein-1. Our study demonstrates that GLO1 is a
      novel metabolic oncogene of the 6p21 amplicon, which promotes tumor growth and
      aberrant transcriptional signals via regulating cellular metabolic activities for
      energy production and could be a potential therapeutic target in gastric cancer. 

PMID- 24662818
TI  - The transcriptional modulator BCL6 as a molecular target for breast cancer
      therapy.
AB  - Inappropriate expression or activation of transcription factors can drive
      patterns of gene expression, leading to the malignant behavior of breast cancer
      cells. We have found that the transcriptional repressor BCL6 is highly expressed
      in breast cancer cell lines, and its locus is amplified in about half of primary
      breast cancers. To understand how BCL6 regulates gene expression in breast cancer
      cells, we used chromatin immunoprecipitation followed by deep sequencing to
      identify the BCL6 binding sites on a genomic scale. This revealed that BCL6
      regulates a unique cohort of genes in breast cancer cell lines compared with B
      cell lymphomas. Furthermore, BCL6 expression promotes the survival of breast
      cancer cells, and targeting BCL6 with a peptidomimetic inhibitor leads to
      apoptosis of these cells. Finally, combining a BCL6 inhibitor and a signal
      transducer and activator of transcription3 inhibitor provided enhanced cell
      killing in triple-negative breast cancer cell lines, suggesting that combination
      therapy may be particularly useful. Thus, targeting BCL6 alone or in conjunction
      with other signaling pathways may be a useful therapeutic strategy for treating
      breast cancer. 

PMID- 24662819
TI  - Tumor-derived inducible heat-shock protein 70 (HSP70) is an essential component
      of anti-tumor immunity.
AB  - The anti-apoptotic function and tumor-associated expression of heat-shock protein
      70 (HSP70) is consistent with HSP70 functioning as a survival factor to promote
      tumorigenesis. However, its immunomodulatory activities to induce anti-tumor
      immunity predict the suppression of tumor growth. Using the Hsp70.1/3(-/-)(Hsp70(
      /-)) mouse model, we observed that tumor-derived HSP70 was neither required for
      cellular transformation nor for in vivo tumor growth. Hsp70(-/-) murine embryonic
      fibroblasts (MEFs) were transformed by E1A/Ras and generated tumors in
      immunodeficient hosts as efficiently as wild-type (WT) transformants. Comparison
      of Bcr-Abl-mediated transformation of WT and Hsp70(-/-) bone marrow and
      progression of B-cell leukemogenesis in vivo revealed no differences in disease
      onset or survival rates, and EMU-Myc-driven lymphoma in Hsp70(-/-) mice was
      phenotypically indistinguishable from that in WT EMU-Myc mice. However, Hsp70(-/
      ) E1A/Ras MEFs generated significantly larger tumors than their WT counterparts
      in C57BL/6 J immune-competent hosts. Concurrent with this was a reduction in
      intra-tumoral infiltration of innate and adaptive immune cells, including
      macrophages and CD8(+) T cells. Evaluation of several potential mechanisms
      revealed an HSP70-chemokine-like activity to promote cellular migration. These
      observations support a role for tumor-derived HSP70 in facilitating anti-tumor
      immunity to limit tumor growth and highlight the potential consequences of anti
      HSP70 therapy as an efficacious anti-cancer strategy. 

PMID- 24662820
TI  - PKA signaling drives mammary tumorigenesis through Src.
AB  - Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias;
      however, its role in sporadic epithelial cancers is unknown. Here, we show that
      heightened PKA activity in the mammary epithelium generates tumors. Mammary
      restricted biallelic ablation of Prkar1a, which encodes for the critical type-I
      PKA regulatory subunit, induced spontaneous breast tumors characterized by
      enhanced type-II PKA activity. Downstream of this, Src phosphorylation occurs at
      residues serine-17 and tyrosine-416 and mammary cell transformation is driven
      through a mechanism involving Src signaling. The phenotypic consequences of these
      alterations consisted of increased cell proliferation and, accordingly, expansion
      of both luminal and basal epithelial cell populations. In human breast cancer,
      low PRKAR1A/high SRC expression defines basal-like and HER2 breast tumors
      associated with poor clinical outcome. Together, the results of this study define
      a novel molecular mechanism altered in breast carcinogenesis and highlight the
      potential strategy of inhibiting SRC signaling in treating this cancer subtype in
      humans. 

PMID- 24662821
TI  - Involvement of G-quadruplex structures in regulation of human RET gene expression
      by small molecules in human medullary thyroid carcinoma TT cells.
AB  - The RET (rearranged during transfection) proto-oncogene encodes a receptor
      tyrosine kinase for members of the glial cell line-derived neurotrophic factor
      family of extracellular signaling molecules. The activating germline point
      mutations in the RET, which are known to induce oncogenic activation of RET
      tyrosine kinase, are associated with the development of medullary thyroid
      carcinoma (MTC) and pathogenesis of multiple endocrine neoplasia type 2 (MEN2).
      The polypurine/polypyrimidine tract in the proximal promoter region of the human
      RET gene (-51 to -33 relative to transcription start site) is essential for basal
      transcriptional activity of this gene. This tract consists of a guanine-rich
      sequence containing five runs of at least three contiguous guanines separated by
      one or more bases, conforming to a general motif capable of forming an
      intramolecular G-quadruplex. Here, we show that specific G-quadruplex structures
      formed in the RET promoter region act to repress the transcription of this gene,
      and transcription of this gene can be controlled by ligand-mediated G-quadruplex
      stabilization. In this study, NSC194598, a derivative of indeno[1,2,3
      de]quinazoline, was found to be a novel G-quadruplex interactive agent that
      interfered with transcriptional activation of mutated RET gene in human medullary
      thyroid carcinoma TT cells. This compound significantly reduced endogenous RET
      protein levels and increased apoptosis in these cells. Our results provide
      further support for the idea that G-quadruplex structures may have a critical
      role in transcriptional regulation of the RET gene in vivo, providing insight
      into a novel strategy for transcriptional repression of this gene by small
      molecules. 

PMID- 24662822
TI  - DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress.
AB  - The antineoplastic drug hydroxyurea (HU), when used at subtoxic doses, induces
      prolonged replication stress and centrosome amplification. This causes genomic
      instability and increases the malignancy of the recurring tumor. The mechanism of
      centrosome amplification induced by prolonged replication stress, however, is
      still unclear. Here, we examined the involvement of ataxia telangiectasia,
      mutated (ATM), ataxia telangiectasia, mutated and Rad3-related (ATR) and DNA
      dependent protein kinase (DNA-PK) and found that HU-induced centrosome
      amplification was inhibited by the depletion of DNA-PKcs, but not ATM and ATR.
      Inactivation of ATM/ATR in U2OS cells instead caused aneuploidy and cell death.
      We found DNA-PKcs depletion also abrogated ATM phosphorylation, indicating that
      ATM activation during prolonged replication stress depends on DNA-PK. Depletion
      of DNA-PK abrogated checkpoint kinase (Chk)2 activation and partially reduced
      Chk1 activation. Chk2 depletion blocked HU-induced centrosome amplification,
      indicating a function of Chk2 in centrosome amplification. We further found that
      Chk2 was phosphorylated at Thr68 on the mother centriole at late G2 and mitosis
      when unstressed and on all amplified centrioles induced by HU. In summary, we
      have elucidated that DNA-PK/Chk2 signaling induces centrosome amplification upon
      long-term HU treatment, therefore increasing our insight into tumor recurrence
      after initial chemotherapy. 

PMID- 24662824
TI  - The E3 ubiquitin ligase NEDD4 negatively regulates HER3/ErbB3 level and
      signaling.
AB  - HER3/ErbB3, a member of the epidermal growth factor receptor (EGFR) family, has a
      pivotal role in cancer and is emerging as a therapeutic antibody target. In this
      study, we identified NEDD4 (neural precursor cell expressed, developmentally
      downregulated 4) as a novel interaction partner and ubiquitin E3 ligase of human
      HER3. Using molecular and biochemical approaches, we demonstrated that the C
      terminal tail of HER3 interacted with the WW domains of NEDD4 and the interaction
      was independent of neuregulin-1. Short hairpin RNA knockdown of NEDD4 elevated
      HER3 levels and resulted in increased HER3 signaling and cancer cell
      proliferation in vitro and in vivo. A similar inverse relationship between HER3
      and NEDD4 levels was observed in prostate cancer tumor tissues. More importantly,
      the upregulated HER3 expression by NEDD4 knockdown sensitized cancer cells for
      growth inhibition by an anti-HER3 antibody. Taken together, our results suggest
      that low NEDD4 levels may predict activation of HER3 signaling and efficacies of
      anti-HER3 antibody therapies. 

PMID- 24662823
TI  - Synthetic lethal screening reveals FGFR as one of the combinatorial targets to
      overcome resistance to Met-targeted therapy.
AB  - Met is a receptor tyrosine kinase that promotes cancer progression. In addition,
      Met has been implicated in resistance of tumors to various targeted therapies
      such as epidermal growth factor receptor inhibitors in lung cancers, and has been
      prioritized as a key molecular target for cancer therapy. However, the underlying
      mechanism of resistance to Met-targeting drugs is poorly understood. Here, we
      describe screening of 1310 genes to search for key regulators related to drug
      resistance to an anti-Met therapeutic antibody (SAIT301) by using a small
      interfering RNA-based synthetic lethal screening method. We found that knockdown
      of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of
      SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor
      receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting
      drugs. Inhibition of FGFR3 increased target cell apoptosis through the
      suppression of Bcl-xL expression, followed by reduced cancer cell growth in the
      presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors
      substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and
      enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin
      beta3 is another potential target for combination treatment with SAIT301.
      Suppression of integrin beta3 decreased AKT phosphorylation in SAIT301-resistant
      cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant
      to SAIT301. Gene expression analysis using CCLE database shows that cancer cells
      with high levels of FGFR and integrin beta3 are resistant to crizotinib
      treatment, suggesting that FGFR and integrin beta3 could be used as predictive
      markers for Met-targeted therapy and provide a potential therapeutic option to
      overcome acquired and innate resistance for the Met-targeting drugs. 

PMID- 24662825
TI  - Loss of Dlg5 expression promotes the migration and invasion of prostate cancer
      cells via Girdin phosphorylation.
AB  - Dlg5 has been reported to participate in cancer progression; however, its role in
      prostate cancer still remains poorly understood. In this study, we demonstrate
      that Dlg5 is frequently downregulated in prostate cancer. We show here that Dlg5
      is involved in the regulation of cell migration and cancer cell invasion.
      Knockdown of endogenous Dlg5 markedly increased prostate cancer cell migration
      and invasion. Our studies, for the first time, demonstrate the interaction
      between Dlg5 and Girdin, an actin-binding Akt substrate. Importantly, we found
      that levels of Akt-mediated Girdin phosphorylation (p-Girdin-Ser1416) are
      increased in Dlg5-depleted cells. Small interfering RNA directed against Girdin
      and wortmannin treatment, which was found to reduce Girdin phosphorylation,
      impaired the effect of Dlg5 depletion on cell migration. Taken together, our
      findings demonstrate that Dlg5 interacts with and inhibits the activity of
      Girdin, thereby suppressing the migration of prostate cancer cells. 

PMID- 24662826
TI  - Slug is temporally regulated by cyclin E in cell cycle and controls genome
      stability.
AB  - The transcriptional repressor Slug is best known to control epithelial
      mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this
      study, we demonstrate that Slug is temporally regulated during cell cycle
      progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the
      phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation
      and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S
      transition compared with wild-type Slug and greatly leads to downregulation of
      DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and
      Rad17, reduces cell proliferation, delays S-phase progression and contributes to
      genome instability. Our results indicate that Slug has multifaceted roles in
      cancer progression by controlling both EMT and genome stability. 

PMID- 24662827
TI  - Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote
      tumor-associated macrophage infiltration.
AB  - 5-lipoxygenase (5-LOX), a member of the lipoxygenase gene family, is a key enzyme
      assisting in the conversion of arachidonic acid to 5-HETE and leukotrienes. Tumor
      associated macrophages (TAMs) have a critical role in the progression and
      metastasis of many tumors, including ovarian tumors. Moreover, TAMs are often
      found in a high density in the hypoxic areas of tumors. However, the relevant
      mechanisms have not been studied explicitly until now. In this study, we found
      that the expression of 5-LOX strongly correlated with the density of TAMs in
      hypoxic areas of human ovarian tumor tissues. In cultured ovarian cancer cells, 5
      LOX metabolites were increased under hypoxic conditons. Increased 5-LOX
      metabolites from hypoxic ovarian cancer cells promoted migration and invasion of
      macrophages, which was further demonstrated to be mediated by the upregulation of
      matrix metalloproteinase (MMP)-7 expression through the p38 pathway. Besides, we
      also showed that 5-LOX metabolites enhanced the release of tumor necrosis factor
      (TNF-alpha) and heparin-binding epidermal growth factor-like growth factor
      through upregulation of MMP-7. Furthermore, in animal models, Zileuton (a
      selective and specific 5-LOX inhibitor) reduced the MMP-7 expression and the
      number of macrophages infiltrating in the xenograft. Our findings suggest for the
      first time that increased metabolites of 5-LOX from hypoxic ovarian cancer cells
      promote TAM infiltration. These results of this study have immediate
      translational implications for the therapeutic exploitation of TAMs. 

PMID- 24662828
TI  - Exosomal HIF1alpha supports invasive potential of nasopharyngeal carcinoma
      associated LMP1-positive exosomes.
AB  - It has emerged recently that exosomes are potential carriers of pro-tumorigenic
      factors that participate in oncogenesis. However, whether oncogenic transcription
      factors are transduced by exosomes is unknown. Hypoxia-inducible factor-1alpha
      (HIF1alpha) transcriptionally regulates numerous key aspects of tumor development
      and progression by promoting a more aggressive tumor phenotype, characterized by
      increased proliferation and invasiveness coupled with neoangiogenesis. It has
      been shown that the principal oncoprotein of Epstein-Barr virus (EBV), latent
      membrane protein 1 (LMP1), drives oncogenic processes and tumor progression of
      the highly invasive EBV malignancy, nasopharyngeal carcinoma (NPC). We now
      demonstrate that endogenous HIF1alpha is detectable in exosomes and that LMP1
      significantly increases levels of HIF1alpha in exosomes. HIF1 recovered from
      exosomes retains DNA-binding activity and is transcriptionally active in
      recipient cells after exosome uptake. We also show that treatment of EBV-negative
      cells with LMP1-exosomes increases migration and invasiveness of NP cell lines in
      functional assays, which correlates with the phenotype associated with epithelial
      mesenchymal transition (EMT). In addition, we provide evidence that HIF1alpha
      itself participates in exosome-mediated pro-metastatic effects in recipient
      cells, as exosome-mediated delivery of active and inactive forms of HIF1alpha
      results in reciprocal changes in the expression of E- and N-cadherins associated
      with EMT. Further, immunohistochemical analysis of NPC tumor tissues revealed
      direct correlation between protein levels of LMP1 and of the endosome/exosome
      marker tetraspanin, CD63, which suggests an increase in exosome formation in this
      EBV-positive malignancy. We hypothesize that exosome-mediated transfer of
      functional pro-metastatic factors by LMP1-positive NPC cells to surrounding tumor
      cells promotes cancer progression. 

PMID- 24662829
TI  - A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion
      and metastasis.
AB  - Most p53 mutations in human cancers are missense mutations resulting in a full
      length mutant p53 protein. Besides losing tumor suppressor activity, some hotspot
      p53 mutants gain oncogenic functions. This effect is mediated in part, through
      gene expression changes due to inhibition of p63 and p73 by mutant p53 at their
      target gene promoters. Here, we report that the tumor suppressor microRNA let-7i
      is downregulated by mutant p53 in multiple cell lines expressing endogenous
      mutant p53. In breast cancer patients, significantly decreased let-7i levels were
      associated with missense mutations in p53. Chromatin immunoprecipitation and
      promoter luciferase assays established let-7i as a transcriptional target of
      mutant p53 through p63. Introduction of let-7i to mutant p53 cells significantly
      inhibited migration, invasion and metastasis by repressing a network of oncogenes
      including E2F5, LIN28B, MYC and NRAS. Our findings demonstrate that repression of
      let-7i expression by mutant p53 has a key role in enhancing migration, invasion
      and metastasis. 

PMID- 24662830
TI  - Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression
      by triggering Nek2 degradation through a death-trap mechanism.
AB  - Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often
      overexpressed in cancers with poor prognosis. Both are critical mitotic
      regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper
      chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting
      their interaction with small molecules represents an ideal strategy for tackling
      these types of cancers. Here we showed that new derivatives of INH (inhibitor for
      Nek2 and Hec1 binding) bind to Hec1 at amino acids 394-408 on W395, L399 and K400
      residues, effectively blocking Hec1 phosphorylation on S165 by Nek2, and killing
      cancer cells at the nanomolar range. Mechanistically, the D-box (destruction-box)
      region of Nek2 specifically binds to Hec1 at amino acids 408-422, immediately
      adjacent to the INH binding motif. Subsequent binding of Nek2 to INH-bound Hec1
      triggered proteasome-mediated Nek2 degradation, whereas the Hec1 binding
      defective Nek2 mutant, Nek2 R361L, resisted INH-induced Nek2 degradation. This
      finding unveils a novel drug-action mechanism where the binding of INHs to Hec1
      forms a virtual death-trap to trigger Nek2 degradation and eventually cell death.
      Furthermore, analysis of the gene expression profiles of breast cancer patient
      samples revealed that co-elevated expressions of Hec1 and Nek2 correlated with
      the shortest survival. Treatment of mice with this kind of tumor with INHs
      significantly suppressed tumor growth without obvious toxicity. Taken together,
      the new INH derivatives are suitable for translation into clinical application. 

PMID- 24662832
TI  - Basonuclin-1 modulates epithelial plasticity and TGF-beta1-induced loss of
      epithelial cell integrity.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine and
      critically involved in the progression of a variety of cancers. TGF-beta1
      signaling can impair tumor development by its anti-proliferative and pro
      apoptotic features. In contrast, it may actively promote tumor progression and
      cancer cell dissemination by inducing a gradual switch from epithelial towards
      mesenchymal-like cell features (EMT-like), including decreased intercellular
      adhesion. Here, we show that expression of the transcription factor Basonuclin-1
      (Bnc1) modulates TGF-beta1-induced epithelial dedifferentiation of mammary
      epithelial cells. RNAi-mediated repression of Bnc1 resulted in enhanced
      intercellular adhesion and strongly impaired TGF-beta1-dependent sheet
      disintegration and cell scattering. In contrast, forced expression of Bnc1
      modifies plasma membrane/cytoskeletal dynamics and seemingly interferes with the
      initiation of sustainable cell-cell contacts. Follow-up analyses revealed that
      Bnc1 affects the expression of numerous TGF-beta1-responsive genes including
      distinct EMT-related transcription factors, some of which modulate the expression
      of Bnc1 themselves. These results suggest that Bnc1 is part of a transcription
      factor network related to epithelial plasticity with reciprocal feedback-loop
      connections on which Smad-factors integrate TGF-beta1 signaling. Our study
      demonstrates that Bnc1 regulates epithelial plasticity of mammary epithelial
      cells and influences outcome of TGF-beta1 signaling. 

PMID- 24662831
TI  - Targeting Epstein-Barr virus oncoprotein LMP1-mediated glycolysis sensitizes
      nasopharyngeal carcinoma to radiation therapy.
AB  - Our goal in this work was to illustrate the Epstein-Barr virus (EBV)-modulated
      global biochemical profile and provide a novel metabolism-related target to
      improve the therapeutic regimen of nasopharyngeal carcinoma (NPC). We used a
      metabolomics approach to investigate EBV-modulated metabolic changes, and found
      that the exogenous overexpression of the EBV-encoded latent membrane protein 1
      (LMP1) significantly increased glycolysis. The deregulation of several glycolytic
      genes, including hexokinase 2 (HK2), was determined to be responsible for the
      reprogramming of LMP1-mediated glucose metabolism in NPC cells. The upregulation
      of HK2 elevated aerobic glycolysis and facilitated proliferation by blocking
      apoptosis. More importantly, HK2 was positively correlated with LMP1 in NPC
      biopsies, and high HK2 levels were significantly associated with poor overall
      survival of NPC patients following radiation therapy. Knockdown of HK2
      effectively enhanced the sensitivity of LMP1-overexpressing NPC cells to
      irradiation. Finally, c-Myc was demonstrated to be required for LMP1-induced
      upregulation of HK2. The LMP1-mediated attenuation of the PI3-K/Akt-GSK3beta-FBW7
      signaling axis resulted in the stabilization of c-Myc. These findings indicate a
      close relationship between EBV and glycolysis in NPC. Notably, LMP1 is the key
      regulator of the reprogramming of EBV-mediated glycolysis in NPC cells. Given the
      importance of EBV-mediated deregulation of glycolysis, anti-glycolytic therapy
      might represent a worthwhile avenue of exploration in the treatment of EBV
      related cancers. 

PMID- 24662834
TI  - Intratumoral heterogeneity of ADAM23 promotes tumor growth and metastasis through
      LGI4 and nitric oxide signals.
AB  - Intratumoral heterogeneity (ITH) represents an obstacle for cancer diagnosis and
      treatment, but little is known about its functional role in cancer progression.
      The A Desintegrin And Metalloproteinase 23 (ADAM23) gene is epigenetically
      silenced in different types of tumors, and silencing is often associated with
      advanced disease and metastasis. Here, we show that invasive breast tumors
      exhibit significant ADAM23-ITH and that this heterogeneity is critical for tumor
      growth and metastasis. We demonstrate that while loss of ADAM23 expression
      enhances invasion, it causes a severe proliferative deficiency and is not itself
      sufficient to trigger metastasis. Rather, we observed that, in ADAM23-heterotypic
      environments, ADAM23-negative cells promote tumor growth and metastasis by
      enhancing the proliferation and invasion of adjacent A23-positive cells through
      the production of LGI4 (Leucine-rich Glioma Inactivated 4) and nitric oxide (NO).
      Ablation of LGI4 and NO in A23-negative cells significantly attenuates A23
      positive cell proliferation and invasion. Our work denotes a driving role of
      ADAM23-ITH during disease progression, shifting the malignant phenotype from the
      cellular to the tissue level. Our findings also provide insights for therapeutic
      intervention, enforcing the need to ascertain ITH to improve cancer diagnosis and
      therapy. 

PMID- 24662833
TI  - Targeting autophagy overcomes Enzalutamide resistance in castration-resistant
      prostate cancer cells and improves therapeutic response in a xenograft model.
AB  - Macro-autophagy is associated with drug resistance in various cancers and can
      function as an adaptive response to maintain cell survival under metabolic
      stresses, including androgen deprivation. Androgen deprivation or treatment with
      androgen receptor (AR) signaling inhibitor (ARSI), Enzalutamide (MDV-3100, ENZA)
      or bicalutamide induced autophagy in androgen-dependent and in castration
      resistant CaP (castration-resistant prostate cancer (CRPC)) cell lines. The
      autophagic cascade triggered by AR blockage, correlated with the increased light
      chain 3-II/I ratio and ATG-5 expression. Autophagy was observed in a
      subpopulation of C4-2B cells that developed insensitivity to ENZA after sustained
      exposure in culture. Using flow cytometry and clonogenic assays, we showed that
      inhibiting autophagy with clomipramine (CMI), chloroquine or metformin increased
      apoptosis and significantly impaired cell viability. This autophagic process was
      mediated by AMP-dependent protein kinase (AMPK) activation and the suppression of
      mammalian target of rapamycin (mTOR) through Raptor phosphorylation (Serine 792).
      Furthermore, small interfering RNA targeting AMPK significantly inhibited
      autophagy and promoted cell death in CaP cells acutely or chronically exposed to
      ENZA or androgen deprivation, suggesting that autophagy is an important survival
      mechanism in CRPC. Lastly, in vivo studies with mice orthotopically implanted
      with ENZA-resistant cells demonstrated that the combination of ENZA and autophagy
      modulators, CMI or metformin significantly reduced tumor growth when compared
      with control groups (P<0.005). In conclusion, autophagy is as an important
      mechanism of resistance to ARSI in CRPC. Antiandrogen-induced autophagy is
      mediated through the activation of AMPK pathway and the suppression of mTOR
      pathway. Blocking autophagy pharmacologically or genetically significantly
      impairs prostate cancer cell survival in vitro and in vivo, implying the
      therapeutics potential of autophagy inhibitors in the antiandrogen-resistance
      setting. 

PMID- 24662835
TI  - Identification of MAGEA antigens as causal players in the development of
      tamoxifen-resistant breast cancer.
AB  - The antiestrogen tamoxifen is a well-tolerated, effective treatment for estrogen
      receptor-alpha-positive (ER+) breast cancer, but development of resistance
      eventually limits its use. Here we show that expression of MAGEA2, and related
      members of this cancer-testis antigen family, is upregulated in tamoxifen
      resistant tumor cells. Expression of MAGEA2 in tumor lines grown in vitro or as
      xenografts led to continued proliferation in the presence of tamoxifen. At the
      molecular level, we demonstrate that MAGEA2 protein localizes to the nucleus and
      forms complexes with p53 and ERalpha, resulting in repression of the p53 pathway
      but increased ER-dependent signaling. In a series of ER+, tamoxifen-treated
      breast cancer patients, we show a highly significant (P=0.006) association
      between MAGEA (melanoma-associated antigen) expression and reduced overall
      survival, confirming the clinical significance of our observations. 

PMID- 24662836
TI  - PDZ and LIM domain protein 1(PDLIM1)/CLP36 promotes breast cancer cell migration,
      invasion and metastasis through interaction with alpha-actinin.
AB  - Increased CLP36 expression has been found to be closely associated with breast
      cancer progression. However, whether and how it contributes to malignant behavior
      of breast cancer cells were not known. We show here that CLP36 is critical for
      promoting breast cancer cell migration and invasion in vitro and metastasis in
      vivo, whereas it is dispensable for breast cell proliferation and anchorage
      independent growth in vitro and tumor growth in vivo. CLP36 interacted with both
      alpha-actinin-1 and -4 in breast cancer cells. Depletion of either alpha-actinin
      1 or -4 inhibited breast cancer cell migration. Furthermore, mutations inhibiting
      the alpha-actinin-binding activity abolished the ability of CLP36 to promote
      breast cancer cell migration. Finally, depletion of CLP36 or disruption of the
      CLP36-alpha-actinin complex in breast cancer cells substantially inhibited Cdc42
      activation, cell polarization and migration. Our results identify CLP36 as an
      important regulator of breast cancer cell migration and metastasis, and shed
      light on how increased CLP36 expression contributes to the progression of breast
      cancer. 

PMID- 24662837
TI  - Functional characterization of the tumor-suppressor MARCKS in colorectal cancer
      and its association with survival.
AB  - The myristoylated alanine-rich C-kinase substrate (MARCKS) acts as a tumor
      suppressor in a variety of human neoplasms. In colorectal cancers (CRCs), MARCKS
      has been shown to be a preferential target of mutational inactivation in tumors
      following the microsatellite instability (MSI-H) pathway but little is known
      about its impact on intestinal carcinogenesis. To investigate the relevance of
      MARCKS inactivation in more detail, we analyzed 926 MSI-typed CRCs for MARCKS
      expression by immunohistochemistry and studied the functional consequences of
      MARCKS depletion in colorectal cancer cell lines. We found that loss of MARCKS
      expression was not restricted to MSI-H cancers but also occurred in
      microsatellite stable (MSS) tumors, where it was associated with an adverse
      outcome regarding overall survival, cancer-specific and disease-free survival
      (P=0.002, P=0.0018, P=0.0001, respectively; univariate analysis). In MARCKS
      positive MSS colon cancer cell lines (SW480 and SW707) small interfering RNA
      (siRNA)-mediated knockdown of MARCKS conferred resistance to tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. This was
      accompanied by the downregulation of the TRAIL receptors DR4 and DR5 at the cell
      surface and activation of AKT signaling. Inhibition of AKT signaling and
      transient overexpression of wild-type MARCKS, but not of MARCKS lacking the
      effector domain (ED), abolished the anti-apoptotic effect. In conclusion, our
      data show that inactivation of MARCKS is common in CRCs and is associated with
      adverse outcome in MSS cancers. The finding that MARCKS acts as a mediator of
      apoptosis in MSS CRC cells adds a novel tumor-suppressing function to the so far
      established roles of MARCKS in cell motility and proliferation and can explain
      the prognostic effect of MARCKS depletion in MSS CRC. 

PMID- 24662838
TI  - Assessment of optic nerve head drusen using enhanced depth imaging and swept
      source optical coherence tomography.
AB  - BACKGROUND: Optic nerve head drusen (ONHD) are calcific deposits buried or at the
      surface of the optic disc. Although ONHD may be associated with progressive
      visual field defects, the mechanism of drusen-related field loss is poorly
      understood. Methods for detecting and imaging disc drusen include B-scan
      ultrasonography, fundus autofluorescence, and optical coherence tomography (OCT).
      These modalities are useful for drusen detection but are limited by low
      resolution or poor penetration of deep structures. This review was designed to
      assess the potential role of new OCT technologies in imaging ONHD. EVIDENCE
      ACQUISITION: Critical appraisal of published literature and comparison of new
      imaging devices to established technology. RESULTS: The new imaging modalities of
      enhanced depth imaging optical coherence tomography (EDI-OCT) and swept source
      optical coherence tomography (SS-OCT) are able to provide unprecedented in vivo
      detail of ONHD. Using these devices it is now possible to quantify optic disc
      drusen dimensions and assess integrity of neighboring retinal structures,
      including the retinal nerve fiber layer. CONCLUSIONS: EDI-OCT and SS-OCT have the
      potential to allow better detection of longitudinal changes in drusen and neural
      retina and improve our understanding of drusen-related visual field loss.

PMID- 24662839
TI  - Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and
      promotes tumor metastasis in epithelial ovarian cancer.
AB  - OBJECTIVES: Although long non-coding RNAs (lncRNAs) are emerging as new
      regulators in the cancer paradigm, the involvement of lncRNAs in epithelial
      ovarian cancer (EOC) is just beginning to be studied. In this study, we focused
      on lncRNA HOX transcript antisense RNA (HOTAIR) and investigated its expression
      pattern, clinical significance, and biological function in EOC. METHODS: HOTAIR
      expression in EOC tissues was examined and its correlation with
      clinicopathological factors and patient prognosis was analyzed. A series of in
      vitro and in vivo assays were performed to understand the role of HOTAIR in EOC
      metastasis. RESULTS: HOTAIR expression was elevated in EOC tissues, and HOTAIR
      levels were highly positively correlated with the FIGO stage, the histological
      grade of the tumor, lymph node metastasis, and reduced overall survival (OS) and
      disease-free survival (DFS). A multivariate analysis showed that HOTAIR
      expression is an independent prognostic factor of OS and DFS in patients with
      EOC. Additionally, the results of in vitro assays showed that the suppression of
      HOTAIR expression in the three highly metastatic EOC cell lines (SKOV3.ip1,
      HO8910-PM, and HEY-A8) significantly reduced cell migration/invasion. The results
      of in vivo assays further confirmed the pro-metastatic effects of HOTAIR.
      Moreover, the pro-metastatic effects of HOTAIR were partially mediated by the
      regulation of certain matrix metalloproteinases (MMPs) and epithelial-to
      mesenchymal transition (EMT)-related genes. CONCLUSIONS: Our data suggest that
      HOTAIR plays a vital role in EOC metastasis and could represent a novel
      prognostic marker and potential therapeutic target in patients with EOC.

PMID- 24662840
TI  - In brief: warning against use of valproate for migraine prevention during
      pregnancy.

PMID- 24662841
TI  - Dimethyl fumarate (Tecfidera) for multiple sclerosis.

PMID- 24662842
TI  - Lubiprostone (Amitiza) for opioid-induced constipation.

PMID- 24662843
TI  - Current treatment options for alcohol-related liver disease.
AB  - PURPOSE OF REVIEW: The burden of alcohol on global health is increasing, and
      there is a strong relationship between population alcohol consumption and liver
      related deaths. As alcohol-related liver disease (ArLD) often develops with no
      signs or symptoms, the prevention of liver disease relies on the recognition of
      harmful drinking and screening of those patients at risk for early markers of
      liver disease. RECENT FINDINGS: A robust method of screening patients at risk of
      ArLD is essential. Once a patient develops ArLD, abstinence and early recognition
      of its complications are keys to improving outcomes. Corticosteroids remain the
      mainstay treatment in alcoholic hepatitis pending the results from large
      multicentre trials. More recently, there has been an increased interest in the
      use of rifaximin and albumin in various settings of ArLD. SUMMARY: Advances in
      the treatment of ArLD and its complications, such as alcoholic hepatitis, will
      allow a greater proportion of patients chance for their liver to recover.
      However, new strategies to detect and intervene in those patients at higher risk
      of ArLD are likely to have the greatest overall impact.

PMID- 24662844
TI  - Health services and policy research in hepatology.
AB  - PURPOSE OF REVIEW: This article examines recent health services and policy
      research studies in hepatology and liver transplantation. RECENT FINDINGS:
      Critical issues include access to medical care, timeliness of referral and
      consultation, resource utilization in clinical practice, comparative
      effectiveness research, and the evaluation of care delivery models. Despite
      policymaking efforts, there continues to be unwarranted variation in access to
      subspecialty care and liver transplantation services based on race and geographic
      location. Variations in primary care and specialist awareness of practice
      guidelines for liver disease contribute to disparities in appropriateness and
      timeliness of treatments. Defining the cost-effectiveness of increased resource
      utilization for novel antiviral therapies and liver transplantation continues to
      stimulate controversy. Few comparative effectiveness studies in hepatology exist
      to date, yet a growing number of analyses using national datasets will help
      inform policy in this arena. Identifying care delivery models that demonstrate
      high value for populations with chronic liver disease is critical in the context
      of recent healthcare reform efforts. SUMMARY: Health services and policy research
      is a growing field of investigation in hepatology and liver transplantation.
      Further emphasis on research training and workforce development in this area will
      be critical for understanding and improving patient-centered outcomes for this
      population.

PMID- 24662845
TI  - Therapeutic effect of sildenafil on blast-induced tinnitus and auditory
      impairment.
AB  - Blast-induced tinnitus, along with associated auditory impairment and traumatic
      brain injury, is a primary concern facing military service members. To search for
      treatment, we investigated the therapeutic effects of sildenafil, a
      phosphodiesterase-5 inhibitor, given its vasodilatory effects and evidence
      suggesting its beneficial effects on noise-induced hearing loss. Rats were
      subjected to three consecutive blast exposures at 22 psi and were monitored for
      tinnitus using a gap-detection acoustic startle reflex paradigm. Hearing
      thresholds and detection were tested using auditory brainstem responses and
      prepulse inhibition, respectively. Blasted rats were either treated with
      sildenafil or tap water following blast exposure, while age-matched sham control
      rats were treated with sildenafil and no blast exposure. Our results showed that
      sildenafil did not effectively prevent acute tinnitus onset and hearing
      impairment. Instead, sildenafil significantly suppressed high-frequency tinnitus
      from 3 to 6 weeks after blast exposure and reduced hearing impairment during the
      first week after blast exposure. Complex results were observed in the startle
      force data, where sildenafil-treated rats displayed significantly reduced startle
      force compared to the untreated blasted group, suggesting possible mitigation of
      traumatic brain injury and suppression of hyperacusis-like percepts. Taken
      together, sildenafil showed a therapeutic effect on blast-induced tinnitus and
      audiological impairment in a time-dependent manner. Other regimens such as higher
      dosage prior to blast exposure and combination with other treatments deserve
      further investigation to optimize the therapeutic effects.

PMID- 24662846
TI  - Vision and proprioception do not influence the excitability of the
      corticomotoneuronal pathway during upright standing in young and elderly adults.
AB  - This study investigated the influence of vision and proprioception on the
      excitability of direct corticospinal (corticomotoneuronal) pathway to the soleus
      in young and elderly adults during upright standing. Ten young and 10 elderly
      adults stood upright on a rigid surface with eyes open or closed, and on foam mat
      with eyes open. The corticomotoneuronal excitability was investigated by
      assessing facilitation of the soleus H-reflex induced by subthreshold
      transcranial magnetic stimulation (TMS). The torque produced by the plantar
      flexor muscles during a maximal voluntary contraction was also measured. The
      maximal plantar flexion torque was significantly lower in elderly than in young
      adults (p<0.05). The activity of leg muscles, recorded by electromyography (EMG)
      was greater in elderly than in young adults regardless of balance conditions
      (p<0.05), and greater when standing on foam than in the other conditions
      (p<0.05), regardless of age. The H-reflex facilitation was greater for elderly
      [182.9 (45)%] than young adults [130.5 (33.1)%; p<0.05] but did not differ across
      sensory conditions (p>0.05). However, the amplitude of the H reflex conditioned
      by TMS relative to the amplitude of the test H reflex ratio was positively
      associated with EMG activity of the plantar flexor muscles during upright
      standing (r(2)=0.47; p<0.001). These results indicate that regardless of age the
      excitability of the corticomotoneuronal pathway is not modulated with changes in
      the sensory conditions during upright standing. Nonetheless, the
      corticomotoneural drive to control leg muscle during upright standing increases
      with the level of soleus muscle activity. 

PMID- 24662847
TI  - The dense core vesicle protein IA-2, but not IA-2beta, is required for active
      avoidance learning.
AB  - The islet-antigens IA-2 and IA-2beta are major autoantigens in type-1 diabetes
      and transmembrane proteins in dense core vesicles (DCV). Recently we showed that
      deletion of both IA-2 and IA-2beta alters the secretion of hormones and
      neurotransmitters and impairs behavior and learning. The present study was
      designed to evaluate the contribution to learning of each of these genes by using
      single knockout (SKO) and double knockout (DKO) mice in an active avoidance test.
      After 5 days of training, wild-type (WT) mice showed 60-70% active avoidance
      responses, whereas the DKO mice showed only 10-15% active avoidance responses.
      The degree of active avoidance responses in the IA-2 SKO mice was similar to that
      of the DKO mice, but in contrast, the IA-2beta SKO mice behaved like WT mice
      showing 60-70% active avoidance responses. Molecular studies revealed a marked
      decrease in the phosphorylation of the cAMP response element-binding protein
      (CREB) and Ca(2+)/calmodulin-dependent protein kinase II (CAMKII) in the striatum
      and hippocampus of the IA-2 SKO and DKO mice, but not in the IA-2beta SKO mice.
      To evaluate the role of CREB and CAMKII in the SKO and DKO mice, GBR-12909, which
      selectively blocks the dopamine uptake transporter and increases CREB and CAMKII
      phosphorylation, was administered. GBR-12909 restored the phosphorylation of CREB
      and CAMKII and increased active avoidance learning in the DKO and IA-2 SKO to
      near the normal levels found in the WT and IA-2beta SKO mice. We conclude that in
      the absence of the DCV protein IA-2, active avoidance learning is impaired.

PMID- 24662848
TI  - Antidepressant-like effect of nitric oxide synthase inhibitors and sildenafil
      against lipopolysaccharide-induced depressive-like behavior in mice.
AB  - Inflammation, oxidative and nitrosative stress underlie depression being assessed
      in rodents by the systemic administration of lipopolysacharide (LPS). There is an
      increasing body of evidence of an involvement of nitric oxide (NO) pathway in
      depression, but this issue was not investigated in LPS-induced model. Thus,
      herein we evaluated the effects of NO-pathway-modulating drugs, named
      aminoguanidine, l-NAME, sildenafil and l-arginine, on the behavioral (forced
      swimming test [FST], sucrose preference [SPT] and prepulse inhibition [PPI] of
      the startle) and neurochemical (glutathione [GSH], lipid peroxidation, IL-1beta)
      alterations in the prefrontal cortex, hippocampus and striatum as well as in BDNF
      levels in the hippocampus 24h after LPS (0.5mg/kg, i.p.) administration, a time
      point related to depressive-like behavior. Twenty-four hours post LPS there was
      an increase in immobility time in the FST, decrease in sucrose preference and PPI
      levels accompanied by a decrease in GSH levels and an increase in lipid
      peroxidation, IL-1beta and hippocampal BDNF levels suggestive of a depressive
      like state. The pretreatment with the NOS inhibitors, l-NAME and aminoguanidine
      as well as sildenafil prevented the behavioral and neurochemical alterations
      induced by LPS, although sildenafil and l-NAME were not able to prevent the
      increase in hippocampal BDNF levels induced by LPS. The iNOS inhibitor,
      aminoguanidine, and imipramine prevented all behavioral and neurochemical
      alterations induced by LPS. l-arginine did not prevent the alterations in
      immobility time, sucrose preference and GSH induced by LPS. Taken together our
      results show that the NO-cGMP pathway is important in the modulation of the
      depressive-like alterations induced by LPS. 

PMID- 24662850
TI  - Synergistic activity between primary visual neurons.
AB  - Cortical microcircuitry plays a pivotal role in encoding sensory information
      reaching the cortex. However, the fundamental knowledge concerning the mechanisms
      that govern feature-encoding by these sub-networks is still sparse. Here, we show
      through multi-electrode recordings in V1 of conventionally prepared anesthetized
      cats, that an avalanche of synergistic neural activity occurs between
      functionally connected neurons in a cell-assembly in response to the presented
      stimulus. The results specifically show that once the reference neuron spikes in
      a connected neuron-pair, it facilitates the response of its companion (target)
      neuron for 50ms and, thereafter, the excitability of the target neuron declines.
      On the other hand, the functionally unconnected neurons do not facilitate each
      other's activity within the 50-ms time-window. The added excitation
      (facilitation) of connected neurons is almost four times the responsiveness of
      unconnected neurons. This suggests that connectedness confers the added
      excitability to neurons; consequently leading to feature-encoding within the
      emergent 50-ms-period. Furthermore, the facilitation significantly decreases as a
      function of orientation selectivity spread. 

PMID- 24662849
TI  - Sequence variations at I260 and A1731 contribute to persistent currents in
      Drosophila sodium channels.
AB  - Tetrodotoxin-sensitive persistent sodium currents, INaP, that activate at
      subthreshold voltages, have been detected in numerous vertebrate and invertebrate
      neurons. These currents are believed to be critical for regulating neuronal
      excitability. However, the molecular mechanism underlying INaP is controversial.
      In this study, we identified an INaP with a broad range of voltage dependence,
      from -60mV to 20mV, in a Drosophila sodium channel variant expressed in Xenopus
      oocytes. Mutational analysis revealed that two variant-specific amino acid
      changes, I260T in the S4-S5 linker of domain I (ILS4-S5) and A1731V in the
      voltage sensor S4 of domain IV (IVS4), contribute to the INaP. I260T is critical
      for the portion of INaP at hyperpolarized potentials. The T260-mediated INaP is
      likely the result of window currents flowing in the voltage range where the
      activation and inactivation curves overlap. A1731V is responsible for impaired
      inactivation and contributes to the portion of INaP at depolarized potentials.
      Furthermore, A1731V causes enhanced activity of two site-3 toxins which induce
      persistent currents by inhibiting the outward movement of IVS4, suggesting that
      A1731V inhibits the outward movement of IVS4. These results provided molecular
      evidence for the involvement of distinct mechanisms in the generation of INaP:
      T260 contributes to INaP via enhancement of the window current, whereas V1731
      impairs fast inactivation probably by inhibiting the outward movement of IVS4. 

PMID- 24662851
TI  - The effectiveness of a statewide trauma call center in reducing time to
      definitive care for severely injured patients.
AB  - BACKGROUND: The state of Arkansas developed and implemented a comprehensive
      inclusive trauma system in July 2010. The Arkansas Trauma Communication Center
      (ATCC) is a central component in the system, designed to facilitate both scene
      transports and interfacility transfers within the state. The first 18 months of
      operations were examined to evaluate the relationship between ATCC use and
      emergency department (ED) length of stay (LOS) at sending facilities for patients
      who require urgent care. METHODS: ATCC data were linked to the Arkansas Trauma
      Registry using unique identifiers. Patients younger than 15 years were excluded
      from the analysis. Patients older than 15 years with significant injury requiring
      interfacility transfer were the study population. Significant injury was defined
      as those with hypotension (systolic blood pressure < 90 mm Hg) or Glasgow Coma
      Scale (GCS) score less than 9 at the sending facility or Injury Severity Score
      (ISS) of 16 or greater at the definitive care facility. This cohort was
      stratified by the use of the ATCC, and ED LOS was determined. RESULTS: The study
      population who met the inclusion criteria was 856; 632 (74%) of whom used the
      ATCC and 224 (26%) did not use the ATCC for interfacility transfers. There were
      no statistically significant differences noted between these two groups regarding
      ISS, systolic blood pressure, and GCS score. The ATCC was associated with a 21
      minute reduction in the ED LOS at the sending facility when controlling for all
      other factors. (p = 0.005). CONCLUSION: In the first 18 months following
      inception, the ATCC has been effective in expediting the transfer process and
      thus reducing the time to definitive care for severely injured patients. ATCC use
      has improved since inception and is now a contract deliverable for trauma
      hospitals based on these early results. LEVEL OF EVIDENCE: Therapeutic study,
      level III.

PMID- 24662852
TI  - The epidemiology of trauma-related mortality in the United States from 2002 to
      2010.
AB  - BACKGROUND: Epidemiologic trends in trauma-related mortality in the United States
      require updating and characterization. We hypothesized that during the past
      decade, there have been changing trends in mortality that are associated with
      multiple public health and health care-related factors. METHODS: Multiple sources
      were queried for the period of 2002 to 2010: the National Trauma Data Bank, the
      National Centers for Disease Control, the National Highway Traffic Safety
      Administration, the Nationwide Emergency Department Sample, and the US Census
      Bureau. The incidence of injury and mortality for motor vehicle traffic (MVT)
      collisions, firearms, and falls were determined using National Centers for
      Disease Control data. National Highway Traffic Safety Administration data were
      used to determine motor vehicle collision information. Injury severity data were
      derived from the Nationwide Emergency Department Sample and National Trauma Data
      Bank. Analysis of mortality trends by year was performed using the Cochran
      Armitage test for trend. Time-trend multivariable Poisson regression was used to
      determine risk-adjusted mortality over time. RESULTS: From 2002 to 2010, the
      total trauma-related mortality decreased by 6% (p < 0.01). However, mortality
      trends differed by mechanism. There was a 27% decrease in the MVT death rate
      associated with a 20% decrease in motor vehicle collisions, 19% decrease in the
      number of occupant injuries per collision, lower injury severity, and improved
      outcomes at trauma centers. While firearm-related mortality remained relatively
      unchanged, mortality caused by firearm suicides increased, whereas homicide
      associated mortality decreased (p < 0.001 for both). In contrast, fall-related
      mortality increased by 46% (5.95-8.70, p < 0.01). CONCLUSION: MVT mortality rates
      have decreased during the last decade, owing in part to decreases in the number
      and severity of injuries. Conversely, fall-related mortality is increasing and is
      projected to exceed both MVT and firearm mortality rates should current trends
      continue. Trauma systems and injury prevention programs will need to take into
      account these changing trends to best accommodate the needs of the injured
      population. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 24662853
TI  - Epidemiology and risk factors of multiple-organ failure after multiple trauma: an
      analysis of 31,154 patients from the TraumaRegister DGU.
AB  - BACKGROUND: In the severely injured who survive the early posttraumatic phase,
      multiple-organ failure (MOF) is the main cause of morbidity and mortality. An
      enhanced prediction of MOF might influence individual monitoring and therapy of
      severely injured patients. METHODS: We performed a retrospective analysis of a
      nationwide prospective database, the TraumaRegister DGU of the German Trauma
      Society. Patients with complete data sets (2002-2011) and a relevant trauma load
      (Injury Severity Score [ISS] >= 16), who were admitted to an intensive care unit,
      were included. RESULTS: Of a total of 31,154 patients enclosed in this study,
      10,201 (32.7%) developed an MOF according to the Sequential Organ Failure
      Assessment score. During the study period, mortality of all patients decreased
      from 18.1% in 2002 to 15.3% in 2011 (p < 0.001). Meanwhile, MOF occurred
      significantly more often (24.6% in 2002 vs. 31.5% in 2011, p < 0.001), but
      mortality of MOF patients decreased (42.6% vs. 33.3%, p < 0.001). MOF patients
      who died survived 2 days less (11 days in 2002 vs. 8.9 days in 2011, p < 0.001).
      Independent risk factors for the development of MOF following severe trauma were
      age, ISS, head Abbreviated Injury Scale (AIS) score of 3 or higher, thoracic AIS
      score of 3 or higher, male sex, Glasgow Coma Scale (GCS) score of 8 or less, mass
      transfusion, base excess of less than -3, systolic blood pressure less than 90 mm
      Hg at admission, and coagulopathy. CONCLUSION: Over one decade, we observed an
      ongoing decrease of mortality after multiple trauma, accompanied by decreasing
      mortality in the subgroup with MOF. However, incidence of MOF in the severely
      injured increased significantly. Thus, MOF after multiple trauma remains a
      challenge in intensive care. The risk factors from multivariate analysis could be
      instrumental in anticipating the early development of MOF. Furthermore, a
      reliable prediction model might be supportive for patient enrolment in trauma
      studies, in which MOF marks the primary end point. LEVEL OF EVIDENCE:
      Epidemiologic study, level III.

PMID- 24662854
TI  - Endovascular Skills for Trauma and Resuscitative Surgery (ESTARS) course:
      curriculum development, content validation, and program assessment.
AB  - BACKGROUND: The management of hemorrhage shock requires support of central aortic
      pressure including perfusion to the brain and heart as well as measures to
      control bleeding. Emerging endovascular techniques including resuscitative
      endovascular balloon occlusion of the aorta serve as potential lifesaving
      adjuncts in this setting. The Endovascular Skills for Trauma and Resuscitative
      Surgery (ESTARS) course was developed to provide fundamental endovascular
      training for trauma surgeons. METHODS: ESTARS 2-day course incorporated
      pretest/posttest examinations, precourse materials, lectures, endovascular and
      open vascular instruments, Vascular Intervention System Trainer endovascular
      simulator, and live animal laboratories for training and testing. Curriculum
      included endovascular techniques for trauma; review of wires, sheaths, and
      catheters; as well as regional vascular injury management. Animal laboratories
      integrated arterial access, angiography, coil embolization, resuscitative
      endovascular balloon occlusion of the aorta, control of iliac artery injury, and
      vascular shunt placement. Students completed a knowledge test
      (precourse/postcourse) and a summative skills assessment. The test measured
      knowledge and judgment in vascular injury management as defined in the course
      objectives. Vascular Intervention System Trainer and animal laboratory were used
      for final examinations. Subjective performance was graded by expert observers
      using a global assessment scale and performance metrics. RESULTS: Four pilot
      ESTARS courses were completed, with four participants each. Knowledge and
      performance significantly improved after ESTARS. Mean test examination scores
      increased by 77% to 85%, with a mean change of 9 percentage points [paired t (15)
      = 7.82, p < 0.0001]. The test was unidimensional (Cronbach's alpha = 0.67).
      Technical skill significantly improved for both endovascular simulation and live
      animal laboratory examinations. All participants passed the live animal
      laboratory practical examination. CONCLUSION: The ESTARS curriculum is effective
      at teaching a basic set of endovascular skills for resuscitation and hemorrhage
      control to trauma surgeons. ESTARS was confirmed as a stepwise and hierarchical
      curriculum demonstrating measurable improvements in performance metrics and
      should serve as a model for future competency-based structured training in
      endovascular trauma skills.

PMID- 24662855
TI  - Thromboelastogram-guided enoxaparin dosing does not confer protection from deep
      venous thrombosis: a randomized controlled pilot trial.
AB  - BACKGROUND: The incidence of deep venous thrombosis (DVT) remains high in general
      surgery and trauma patients despite widespread prophylaxis with enoxaparin. A
      recent study demonstrated decreased incidence of DVT if patients on enoxaparin
      had a change in R time (DeltaR) of greater than 1 minute when heparinase
      activated thromboelastography (TEG) was compared with normal TEG. We hypothesized
      that using DeltaR-guided dosing would result in decreased DVT rates. METHODS: A
      prospective, randomized controlled trial was performed at a Level 1 trauma
      center. Both trauma and general surgery patients were included. Upon enrollment,
      demographic data including age, sex, body mass index, and Acute Physiology and
      Chronic Health Evaluation II score were obtained. Enrolled patients were
      randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted
      patients underwent daily enoxaparin titration to achieve an DeltaR of 1 minute to
      2 minutes. Venous thromboembolism screening was performed per institutional
      protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak
      enoxaparin concentrations. RESULTS: A total of 87 patients were enrolled. There
      was no difference in demographic data between the groups. No pulmonary emboli
      were identified. The control group had a DVT rate of 16%, while the experimental
      group had a rate of 14% (p = nonsignificant). The experimental group's median
      enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the
      control (p < 0.01). TEG DeltaR was not different between the control and
      experimental groups. Beginning at Day 3, anti-Xa levels were higher in the
      experimental group (p < 0.05). There was no difference in AT-III activity between
      the two groups; 67% of the patients demonstrated AT-III deficiency. CONCLUSION:
      TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity,
      which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate
      and increase DeltaR despite increased dosing and increased anti-Xa activity is
      consistent with the high rate of AT-III deficiency detected in this study cohort.
      These data suggest that the future of DVT prevention may not lie in the
      optimization of low molecular weight heparin therapy but rather in compounds that
      increase antithrombin directly or operate independently of the AT-III pathway.
      LEVEL OF EVIDENCE: Therapeutic study, level III.

PMID- 24662856
TI  - Decompressive craniectomy or medical management for refractory intracranial
      hypertension: an AAST-MIT propensity score analysis.
AB  - BACKGROUND: Moderate/severe traumatic brain injury (TBI) management involves
      minimizing cerebral edema to maintain brain oxygen delivery. While medical
      therapy (MT) consisting of diuresis, hyperosmolar therapy, ventriculostomy, and
      barbiturate coma is the standard of care, decompressive craniectomy (DC) for
      refractory intracranial hypertension (ICH) has gained renewed interest. Since TBI
      treatment guidelines consider DC a second-tier intervention after MT failure, we
      sought to determine if early DC (<48 hours) was associated with improved survival
      in patients with refractory ICH. METHODS: Eleven Level 1 trauma centers provided
      clinical data and head computed tomographic scans for patients with a Glasgow
      Coma Scale (GCS) score of 13 or less and radiographic evidence of TBI excluding
      deaths within 48 hours. Computed tomographic scans were graded according to the
      Marshall classification. A propensity score to receive DC (regardless of whether
      DC was performed) was calculated for each patient based on patient
      characteristics, physiology, injury severity, GCS, severity of intracranial
      injury, and treatment center. Patients who actually received a DC were matched to
      patients with similar propensity scores who received MT for analysis. Outcomes
      were compared between early (<48 hours of injury) primary or secondary DC and
      matched controls and then between early primary DC only and matched controls.
      RESULTS: There were 2,602 patients who met the inclusion criteria ,of whom 264
      (10.1%) received DC (either primary or secondary to another cranial procedure)
      and 109 (5%) had a DC that was primary. Variables associated with performing a DC
      included sex, race, intracranial pressure monitor placement, in-house trauma
      attending, traumatic subarachnoid hemorrhage, midline shift, and basal cistern
      compression. There was no survival benefit with early primary DC compared with
      the controls (relative risk, 1.07; 95% confidence interval, 0.67-1.73; p = 0.77),
      and resource use was higher. CONCLUSION: Early DC does not seem to significantly
      improve mortality in patients with refractory ICH compared with MT. Neurosurgeons
      should pause before entertaining this resource-demanding form of therapy. LEVEL
      OF EVIDENCE: Therapeutic care/management, level III.

PMID- 24662857
TI  - Prospective evaluation of intravascular volume status in critically ill patients:
      does inferior vena cava collapsibility correlate with central venous pressure?
AB  - BACKGROUND: In search of a standardized noninvasive assessment of intravascular
      volume status, we prospectively compared the sonographic inferior vena cava
      collapsibility index (IVC-CI) and central venous pressures (CVPs). Our goals
      included the determination of CVP behavior across clinically relevant IVC-CI
      ranges, examination of unitary behavior of IVC-CI with changes in CVP, and
      estimation of the effect of positive end-expiratory pressure (PEEP) on the IVC
      CI/CVP relationship. METHODS: Prospective, observational study was performed in
      surgical/medical intensive care unit patients between October 2009 and July 2013.
      Patients underwent repeated sonographic evaluations of IVC-CI. Demographics,
      illness severity, ventilatory support, CVP, and patient positioning were
      recorded. Correlations were made between CVP groupings (<7, 7-12, 12-18, 19+) and
      IVC-CI ranges (<25, 25-49, 50-74, 75+). Comparison of CVP (2-unit quanta) and IVC
      CI (5-unit quanta) was performed, followed by assessment of per-unit DeltaIVC
      CI/DeltaCVP behavior as well as examination of the effect of PEEP on the IVC
      CI/CVP relationship. RESULTS: We analyzed 320 IVC-CI/CVP measurement pairs from
      79 patients (mean [SD] age, 55.8 [16.8] years; 64.6% male; mean [SD] Acute
      Physiology and Chronic Health Evaluation II, 11.7 [6.21]). Continuous data for
      IVC-CI/CVP correlated poorly (R = 0.177, p < 0.01) and were inversely
      proportional, with CVP less than 7 noted in approximately 10% of the patients for
      IVC-CIs less than 25% and CVP less than 7 observed in approximately 85% of
      patients for IVC-CIs greater than or equal to 75%. Median DeltaIVC-CI per unit
      CVP was 3.25%. Most measurements (361 of 320) were collected in mechanically
      ventilated patients (mean [SD] PEEP, 7.76 [4.11] cm H2O). PEEP-related CVP
      increase was approximately 2 mm Hg to 2.5 mm Hg for IVC-CIs greater than 60% and
      approximately 3 mm Hg to 3.5 mm Hg for IVC-CIs less than 30%. PEEP also resulted
      in lower IVC-CIs at low CVPs, which reversed with increasing CVPs. When IVC-CI
      was examined across increasing PEEP ranges, we noted an inverse relationship
      between the two variables, but this failed to reach statistical significance.
      CONCLUSION: IVC-CI and CVP correlate inversely, with each 1 mm Hg of CVP
      corresponding to 3.3% median DeltaIVC-CI. Low IVC-CI (<25%) is consistent with
      euvolemia/hypervolemia, while IVC-CI greater than 75% suggests intravascular
      volume depletion. The presence of PEEP results in 2 mm Hg to 3.5 mm Hg of CVP
      increase across the IVC-CI spectrum and lower collapsibility at low CVPs.
      Although IVC-CI decreased with increasing degrees of PEEP, this failed to reach
      statistical significance. While this study represents a step forward in the area
      of intravascular volume estimation using IVC-CI, our findings must be applied
      with caution owing to some methodologic limitations. LEVEL OF EVIDENCE:
      Diagnostic study, level III. Prognostic study, level III.

PMID- 24662858
TI  - The BIG (brain injury guidelines) project: defining the management of traumatic
      brain injury by acute care surgeons.
AB  - BACKGROUND: It is becoming a standard practice that any "positive" identification
      of a radiographic intracranial injury requires transfer of the patient to a
      trauma center for observation and repeat head computed tomography (RHCT). The
      purpose of this study was to define guidelines-based on each patient's history,
      physical examination, and initial head CT findings-regarding which patients
      require a period of observation, RHCT, or neurosurgical consultation. METHODS: In
      our retrospective cohort analysis, we reviewed the records of 3,803 blunt
      traumatic brain injury patients during a 4-year period. We classified patients
      according to neurologic examination results, use of intoxicants, anticoagulation
      status, and initial head CT findings. We then developed brain injury guidelines
      (BIG) based on the individual patient's need for observation or hospitalization,
      RHCT, or neurosurgical consultation. RESULTS: A total of 1,232 patients had an
      abnormal head CT finding. In the BIG 1 category, no patients worsened clinically
      or radiographically or required any intervention. BIG 2 category had radiographic
      worsening in 2.6% of the patients. All patients who required neurosurgical
      intervention (13%) were in BIG 3. There was excellent agreement between assigned
      BIG and verified BIG. kappa statistic is equal to 0.98. CONCLUSION: We have
      proposed BIG based on patient's history, neurologic examination, and findings of
      initial head CT scan. These guidelines must be used as supplement to good
      clinical examination while managing patients with traumatic brain injury.
      Prospective validation of the BIG is warranted before its widespread
      implementation. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 24662859
TI  - Do all beta-blockers attenuate the excess hematopoietic progenitor cell
      mobilization from the bone marrow following trauma/hemorrhagic shock?
AB  - BACKGROUND: Severe injury results in increased mobilization of hematopoietic
      progenitor cells (HPC) from the bone marrow (BM) to sites of injury, which may
      contribute to persistent BM dysfunction after trauma. Norepinephrine is a known
      inducer of HPC mobilization, and nonselective beta-blockade with propranolol has
      been shown to decrease mobilization after trauma and hemorrhagic shock (HS). This
      study will determine the role of selective beta-adrenergic receptor blockade in
      HPC mobilization in a combined model of lung contusion (LC) and HS. METHODS: Male
      Sprague-Dawley rats were subjected to LC, followed by 45 minutes of HS. Animals
      were then randomized to receive atenolol (LCHS + beta1B), butoxamine (LCHS +
      beta2B), or SR59230A (LCHS + beta3B) immediately after resuscitation and daily
      for 6 days. Control groups were composed of naive animals. BM cellularity, %HPCs
      in peripheral blood, and plasma granulocyte-colony stimulating factor levels were
      assessed at 3 hours and 7 days. Systemic plasma-mediated effects were evaluated
      in vitro by assessment of BM HPC growth. Injured lung tissue was graded
      histologically by a blinded reader. RESULTS: The use of beta2B or beta3B
      following LCHS restored BM cellularity and significantly decreased HPC
      mobilization. In contrast, beta1B had no effect on HPC mobilization. Only beta3B
      significantly reduced plasma G-CSF levels. When evaluating the plasma systemic
      effects, both beta2B and beta3B significantly improved BM HPC growth as compared
      with LCHS alone. The use of beta2 and beta3 blockade did not affect lung injury
      scores. CONCLUSION: Both beta2 and beta3 blockade can prevent excess HPC
      mobilization and BM dysfunction when given after trauma and HS, and the effects
      seem to be mediated systemically, without adverse effects on subsequent healing.
      Only treatment with beta3 blockade reduced plasma G-CSF levels, suggesting
      different mechanisms for adrenergic-induced G-CSF release and mobilization of
      HPCs. This study adds to the evidence that therapeutic strategies that reduce the
      exaggerated sympathetic stimulation after severe injury are beneficial and reduce
      BM dysfunction.

PMID- 24662860
TI  - Predictive factors for failure of nonoperative management in perforated
      appendicitis.
AB  - BACKGROUND: Identifying patients on admission with perforated appendicitis who
      have phlegmon or abscess initially selected for but likely to fail nonoperative
      management may avoid delays in definitive treatment. METHODS: Patients older than
      15 years presenting to a university tertiary care hospital with perforated
      appendicitis and abscess or phlegmon and planned nonoperative management were
      reviewed. Comorbidities, clinical findings, laboratory markers, radiographic
      findings, and nonsurgical treatments associated with failure of nonoperative
      management were recorded. RESULTS: Eighty-nine patients were identified, and 69
      were managed successfully to discharge without operation. Length of stay was
      greater in the failure group (11 days vs. 5 days, p = 0.001), and intensive care
      unit care was more common (10% vs. 0%, p = 0.049). On univariate and multivariate
      analyses, smoking (odds ratio [OR], 13.20; 95% confidence interval [CI], 1.13
      142; p = 0.039), tachycardia (OR, 4.93; 95% CI, 1.21-20.06; p = 0.026), and
      generalized abdominal tenderness (OR, 5.52; 95% CI, 1.40-21.73; p = 0.015) were
      associated with failure of nonoperative management. On computed tomographic scan,
      the failure group had higher rates of abscess (75% vs. 55%, p = 0.110), and their
      abscesses were more likely smaller than 50 mm (OR, 2.83; 95% CI, 1.01-7.92; p =
      0.043). CONCLUSION: Patients with perforated appendicitis and phlegmon or abscess
      who smoke or present with tachycardia, generalized abdominal tenderness, and
      abscesses smaller than 50 mm are more likely to fail nonoperative management and
      should be considered for early operation. These findings should be validated
      prospectively. LEVEL OF EVIDENCE: Therapeutic study, level III.

PMID- 24662861
TI  - Alveolar macrophage depletion increases the severity of acute inflammation
      following nonlethal unilateral lung contusion in mice.
AB  - BACKGROUND: Lung contusion (LC) is a common injury resulting from blunt thoracic
      trauma. LC is an important risk factor for the development acute lung injury,
      adult respiratory distress syndrome, and ventilator-associated pneumonia, all of
      which increase mortality from trauma. LC produces a nonspecific immune cellular
      response. Neutrophil recruitment is known to increase the severity of
      inflammation during LC. However, the exact role of macrophages in modulating the
      response to LC has not been well described. METHODS: We used a cortical contusion
      impactor to induce unilateral LC in mice. Thoracic micro computed tomographic
      scans of these animals were obtained to document radiologic changes over time
      following LC. To understand the role of macrophages during LC, liposomal
      clodronate was used to deplete macrophage levels before traumatic insult. Acute
      inflammatory attributes after LC were assessed, by measuring pressure-volume
      mechanics; quantifying bronchial alveolar lavage levels of leukocytes, albumin,
      and cytokines; and finally examining lung specimen histopathology at 5, 24, 48,
      and 72 hours after injury. RESULTS: After LC, alveolar macrophage numbers were
      significantly reduced and exhibited slowed recovery. Simultaneously, there was a
      significant increase in bronchial alveolar lavage neutrophil counts. The loss of
      macrophages could be attributed to both cellular apoptosis and necrosis.
      Pretreatment with clodronate increased the severity of lung inflammation as
      measured by worsened pulmonary compliance, increased lung permeability,
      amplification of neutrophil recruitment, and increases in early proinflammatory
      cytokine levels. CONCLUSION: The presence of regulatory alveolar macrophages
      plays an important role in the pathogenesis of acute inflammation following LC.

PMID- 24662862
TI  - The mesenchymal stem cell-derived microvesicles enhance sciatic nerve
      regeneration in rat: a novel approach in peripheral nerve cell therapy.
AB  - BACKGROUND: The accomplishment for desired functional peripheral nerve
      regeneration is still challenging despite various materials and methods. The
      effects of local application of omental adipose mesenchymal stromal cell-derived
      microvesicles (MVs) on peripheral nerve regeneration were studied using a rat
      sciatic nerve transection model. METHODS: A 10-mm gap of sciatic nerve was
      bridged with a chitosan conduit. The rats were divided into five experimental
      groups randomly as follows: cultured undifferentiated omental adipose-derived
      stromal cells, rest mesenchymal stem cell-derived MVs (c-MVs), anti-inflammatory
      mesenchymal stem cell-derived MVs (anti-MVs), proinflammatory mesenchymal stem
      cell-derived MVs (pro-MVs), and negative control (Chit). RESULTS: The functional
      assessment of nerve regeneration (walking track analyses), electrophysiologic
      measurements, muscle mass measurements, as well as histomorphometrical and
      immunohistochemical indices showed drastic improvement in nerve regeneration in c
      MVs and anti-MVs animals compared with pro-MVs animals (p < 0.05). CONCLUSION:
      The anti-inflammatory stem cell-derived MVs can be used as an alternative for the
      improvement of rat sciatic nerve regeneration.

PMID- 24662863
TI  - Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with
      normal saline in a large animal model of multisystem trauma.
AB  - BACKGROUND: Platelet dysfunction following trauma has been identified as an
      independent predictor of mortality. We hypothesized that fresh frozen plasma
      (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9%
      normal saline (NS). METHODS: Twelve swine were subjected to multisystem trauma
      (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with
      hemorrhagic shock (40% of estimated blood volume). Animals were left in shock
      (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with
      three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored
      for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)
      induced platelet aggregation at baseline, after 2 hours of shock following
      resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of
      platelet activation (transforming growth factor beta [TGF-beta], sP-Selectin, and
      CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1],
      vascular cell adhesion molecule 1 [VCAM-1]) were also assayed.
      Thromboelastography was used to measure clotting activity. RESULTS: ADP-induced
      platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5
      U, p < 0.01) following resuscitation. This was associated with higher fibrinogen
      levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM
      1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ.After 6
      hours of observation, ADP-induced platelet aggregation remained higher in the FFP
      group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153
      mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4
      ng/mL, p = 0.05), whereas TGF-beta levels were higher (2,138 pg/mL vs. 1,802
      pg/mL, p = 0.03) in the FFP group. Other markers did not differ.
      Thromboelastography revealed increased clot strength in the FFP group at both
      postresuscitation time points. CONCLUSION: Resuscitation with FFP resulted in an
      immediate and sustained improvement in platelet function and clot strength
      compared with high-volume NS resuscitation. This was associated with an increase
      in fibrinogen levels and an attenuation of endothelial activation.

PMID- 24662865
TI  - Feasibility and transport of packed red blood cells into Special Forces
      operational conditions.
AB  - BACKGROUND: Transfusing packed red blood cells (PRBCs) into Special Forces may
      provide a survival advantage from hemorrhage-induced battlefield injuries;
      however, the effect of the unique operational stressors on RBC integrity is not
      known. METHODS: Pooled PRBCs (20 U) (7 days old), stored in Golden Hour
      containers, were exposed to the following simulated operational stressors: High
      Altitude Low-Opening parachute descent from 30,000 ft, followed by a simulated
      soldier presence patrol in a climatic chamber set to 48  degrees C and 9%
      humidity for 12 hours (test). Biochemical (pH, lactate, potassium, and adenosine
      triphosphate) and biomechanical (percent hemolysis, deformability, and
      morphology) were measured to determine the integrity of PRBCs. RESULTS: The
      simulated parachute descent significantly raised pH (p = 0.025) and potassium (p
      = 0.014) levels compared with the control; however, this was not clinically
      significant. Lactate (mmol/L) and adenosine triphosphate levels (0 MUmol/g Hgb)
      were unaffected (p > 0.05). Potassium and pH levels increased with time but not
      significantly compared with controls. Lactate levels were unaffected with
      time.Mechanical agitation of PRBCs from the simulated soldier presence patrol did
      not significantly affect the biochemical (p >= 0.08) or biomechanical (p >= 0.33)
      parameters compared with control.Hemolysis was found to be less than 0.8% at the
      end of 12 hours. No significant difference in RBC morphology and RBC
      deformability were noted. CONCLUSION: Carrying PRBCs into the austere Special
      Forces environment is feasible as biochemical and biomechanical markers of RBC
      stress remain within published transfusion safety parameters when PRBCs were
      stored in new cold technology containers for 12 hours at 48 degrees C during a
      simulated Special Forces operation.

PMID- 24662864
TI  - Colloid with high fresh frozen plasma/red blood cell resuscitation does not
      reduce postoperative fluid needs.
AB  - BACKGROUND: Recent data suggest that intraoperative (Phase I) colloid (human
      serum albumin [HSA]) and a high fresh frozen plasma (FFP)/red blood cell (RBC)
      resuscitation will reduce postoperative (Phase II) fluid uptake. This study
      compares a noncolloid (balanced electrolyte solution [BES]) plus low (<= 0.35)
      FFP/RBC resuscitation (Group A) with an HSA plus high (>0.35) FFP/RBC
      resuscitation. METHODS: A previous randomized study of 94 patients included 48
      BES patients and 46 HSA patients. A Subgroup A of 25 BES patients with low
      FFP/RBC was compared with a Subgroup D of 21 HSA patients with high FFP/RBC.
      Parameters monitored included Phase I vital signs and resuscitation needs; Phase
      II duration, BES needs, weight gain, and hourly urine output; and postoperative
      plasma volume (PV) by radioiodinated serum albumin (RISA), extracellular fluid
      (ECF) volume by inulin space, and interstitial volume by ECF-PV. RESULTS:
      Admission pulse (132 for A vs. 133 for D), systolic blood pressure (SBP) (74 for
      A vs. 74 for D) and Phase I shock time (SBP < 80 Torr; 25 for A vs. 35 for D)
      were similar. Phase I RBC needs (12.5 +/- 1.3 for A vs. 14.9 +/- 1.7 for D) and
      BES needs (8.4 +/- 0.6 L for A vs. 8.4 +/- 0.6 L for D) were similar. During
      Phase II, D patients had more RBC, comparable BES, and weight gain, with lower
      hourly urine output compared with Group A patients. CONCLUSION: HSA with high
      FFP/RBC does not prevent Phase II fluid uptake and causes lower urine output
      despite increased PV. Colloid reduces glomerular filtration, increases tubular
      reabsorption, and increases ECF, thus, prolonging Phase II. LEVEL OF EVIDENCE:
      Therapeutic study, level IV.

PMID- 24662867
TI  - Evolution in the management of traumatic diaphragmatic injuries: a multicenter
      review.
AB  - BACKGROUND: Traumatic diaphragmatic injury (TDI) is uncommon and has historically
      been identified by chest x-ray and repaired by laparotomy with nonabsorbable
      suture. Blunt TDI was more frequently (90%) detected on the left. With advances
      in imaging and operative techniques, our objective was to evaluate evolution in
      incidence, location, and management of TDI. METHODS: The medical records of
      patients admitted to three Wisconsin regional trauma centers with TDI from 1996
      to 2011 were reviewed. Patients were stratified into blunt and penetrating injury
      and early (1996-2003) and recent (2004-2011) periods. p < 0.05 was significant.
      RESULTS: A total of 454 patients was included, 87% were men. Median Injury
      Severity Score (ISS) was 22 and 19 in the early and recent periods, respectively.
      Diagnostic modality for TDI did not change over time when comparing chest x-ray,
      computed tomography, or intraoperative diagnosis for blunt (p = 0.214) or
      penetrating (p = 0.119) TDI. More right-sided penetrating TDI were identified in
      the recent versus early group (49% vs. 27%). Perihiatal injury was rare (2%).
      Minimally invasive repairs increased in the recent versus early group of
      penetrating TDI (5.8% vs. 0.9%, p = 0.040). Complex repairs (mesh, transposition)
      were required in only three patients. In-hospital mortality was 15% and 4% for
      blunt and penetrating TDIs, respectively (p < 0.001). CONCLUSION: A large
      increase in the frequency of both blunt and penetrating TDIs in our region was
      documented. While no difference was observed regarding diagnosis of blunt TDI
      during the two study periods, our data show a change from historical reports;
      more injuries were detected by computed tomography. An increase in right-sided
      penetrating TDI was also observed. A small but previously unreported incidence of
      perihiatal/pericardial injury occurred with both blunt and penetrating TDIs.
      While the majority of injuries were repaired with laparotomy, minimally invasive
      repairs were used more frequently in the recent period. LEVEL OF EVIDENCE:
      Epidemiologic study, level III. Therapeutic study, level IV.

PMID- 24662866
TI  - Intra-abdominal injury following blunt trauma becomes clinically apparent within
      9 hours.
AB  - BACKGROUND: The diagnosis of blunt abdominal trauma can be challenging and
      resource intensive. Observation with serial clinical assessments plays a major
      role in the evaluation of these patients, but the time required for intra
      abdominal injury to become clinically apparent is unknown. The purpose of this
      study was to determine the amount of time required for an intra-abdominal injury
      to become clinically apparent after blunt abdominal trauma via physical
      examination or commonly followed clinical values. METHODS: A retrospective review
      of patients who sustained blunt trauma resulting in intra-abdominal injury
      between June 2010 and June 2012 at a Level 1 academic trauma center was
      performed. Patient demographics, injuries, and the amount of time from emergency
      department admission to sign or symptom development and subsequent diagnosis were
      recorded. All diagnoses were made by computed tomography or at the time of
      surgery. Patient transfers from other hospitals were excluded. RESULTS: Of 3,574
      blunt trauma patients admitted to the hospital, 285 (8%) experienced intra
      abdominal injuries. The mean (SD) age was 36 (17) years, the majority were male
      (194 patients, 68%) and the mean (SD) Injury Severity Score (ISS) was 21 (14).
      The mean (SD) time from admission to diagnosis via computed tomography or surgery
      was 74 (55) minutes. Eighty patients (28%) required either surgery (78 patients,
      17%) or radiographic embolization (2 patients, 0.7%) for their injury. All
      patients who required intervention demonstrated a sign or symptom of their intra
      abdominal injury within 60 minutes of arrival, although two patients were
      intervened upon in a delayed fashion. All patients with a blunt intra-abdominal
      injury manifested a clinical sign or symptom of their intra-abdominal injury,
      resulting in their diagnosis within 8 hours 25 minutes of arrival to the
      hospital. CONCLUSION: All diagnosed intra-abdominal injuries from blunt trauma
      manifested clinical signs or symptoms that could prompt imaging or intervention,
      leading to their diagnosis within 8 hours 25 minutes of arrival to the hospital.
      All patients who required an intervention for their injury manifested a sign or
      symptom of their injury within 60 minutes of arrival. LEVEL OF EVIDENCE:
      Therapeutic study, level IV. Epidemiologic study, level III.

PMID- 24662868
TI  - Evaluation of 8.0-cm needle at the fourth anterior axillary line for needle chest
      decompression of tension pneumothorax.
AB  - BACKGROUND: Five-centimeter needles at the second intercostal space midclavicular
      line (2MCL) have high failure rates for decompression of tension pneumothorax.
      This study evaluates 8-cm needles directed at the fourth intercostal space
      anterior axillary line (4AAL). METHODS: Retrospective radiographic analysis of
      100 consecutive trauma patients 18 years or older from January to September 2011.
      Measurements of chest wall thickness (CWT) and depth to vital structure (DVS)
      were obtained at 2MCL and 4AAL. 4AAL measurements were taken based on two angles:
      closest vital structure and perpendicular to the chest wall. Primary outcome
      measures were radiographic decompression (RD) (defined as CWT < 80 mm) and
      radiographic noninjury (RNI) (DVS > 80 mm) of 8-cm needles at 4AAL. Secondary
      outcome measures are effect of angle of entry on RNI at 4AAL, RD and RNI of 8-cm
      needles at 2MCL, and comparison of 5-cm needles with 8-cm needles at both
      locations. RESULTS: Eighty-four percent of the patients were male, with mean
      Injury Severity Score (ISS) of 17.7 (range, 1.0-66.0) and body mass index of 26.8
      (16.5-48.4). Mean CWT at 4AAL ranged from 37.6 mm to 39.9 mm, significantly
      thinner than mean CWT at 2MCL (43.3-46.7 mm). Eight-centimeter needle RD was more
      than 96% at both 4AAL and 2MCL. Five-centimeter RD ranged from 66% to 81% at all
      sites. Mean DVS at 4AAL ranged from 91.8 mm to 128.0 mm. RNI at all sites was
      more than 91% except at left 4AAL, when taken to the closest vital structure
      (mean DVS, 91.8 mm), with 68% RNI. Perpendicular entry increased DVS to 109.4 mm
      and subsequent RNI to 91%. Five-centimeter RNI at all sites was more than 99%.
      CONCLUSION: CWT at 4AAL is significantly thinner than 2MCL. Based on radiographic
      measurements, 8-cm catheters have a higher chance of pleural decompression when
      compared with 5-cm catheters. Steeper angle of entry at 4AAL improves 8-cm
      noninjury rates to more than 91%. LEVEL OF EVIDENCE: Therapeutic/care management
      study, level IV.

PMID- 24662869
TI  - Optimizing trauma system design: the GEOS (Geospatial Evaluation of Systems of
      Trauma Care) approach.
AB  - BACKGROUND: Trauma systems have been shown to reduce death and disability from
      injury but must be appropriately configured. A systematic approach to trauma
      system design can help maximize geospatial effectiveness and reassure
      stakeholders that the best configuration has been chosen. METHODS: This article
      describes the GEOS [Geospatial Evaluation of Systems of Trauma Care] methodology,
      a mathematical modeling of a population-based data set, which aims to derive
      geospatially optimized trauma system configurations for a geographically defined
      setting. GEOS considers a region's spatial injury profile and the available
      resources and uses a combination of travel time analysis and multiobjective
      optimization. The methodology is described in general and with regard to its
      application to our case study of Scotland. RESULTS: The primary outcome will be
      trauma system configuration. CONCLUSION: GEOS will contribute to the design of a
      trauma system for Scotland. The methodology is flexible and inherently
      transferable to other settings and could also be used to provide assurance that
      the configuration of existing trauma systems is fit for purpose.

PMID- 24662870
TI  - Variability in California triage from 2005 to 2009: a population-based
      longitudinal study of severely injured patients.
AB  - BACKGROUND: Timely access to trauma care requires that severely injured patients
      are ultimately triaged to trauma centers. We sought to determine triage patterns
      for the injured population within the state of California to determine those
      factors associated with undertriage. METHODS: We conducted a retrospective
      analysis of all hospital visits in California using the Office of Statewide
      Health Planning and Development Database from January 1, 2005, and December 31,
      2009. All visits associated with injury were linked longitudinally. Sixty-day and
      one-year mortality was determined using vital statistics data. Primary field
      triage was defined as field triage to a Level I/II trauma center; retriage was
      defined as initial triage to a non-Level I/II center followed by transfer to a
      Level I/II. Regions were organized by local emergency medical services agencies.
      The primary outcomes were triage patterns and mortality. RESULTS: The undertriage
      rate was 35% (n = 20,988) but was variable across regions (12-87%). Primary field
      triage ranged from 7% to 77%. Retriage rates not only were overall low (6% of all
      severely injured patients) but also varied by region (1-38%). In adjusted
      analysis, factors associated with a lower odds ratio (OR) of primary field triage
      included the following: age of 55 years or greater (OR, 0.78; p = 0.001), female
      sex (OR, 0.88; p = 0.014), greater number of comorbidities (OR, 0.92; p < 0.001),
      and fall mechanism versus motor vehicle collision (OR, 0.54; p < 0.001). One-year
      mortality was higher for undertriaged patients (25% vs. 16% and 18% for primary
      field and retriage, respectively, p < 0.001). CONCLUSION: This is the first study
      to create a longitudinal database of all emergency department visits,
      hospitalizations, and long-term mortality for every severely injured patient
      within an entire state during a 5-year period. Undertriage varied substantially
      by region and was associated with multiple factors including access to care and
      patient factors. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 24662871
TI  - A 26-year comparative review of United Kingdom helicopter emergency medical
      services crashes and serious incidents.
AB  - BACKGROUND: The use of helicopter emergency medical services (HEMS) has increased
      substantially in the United Kingdom since 1987. There are currently no data on
      the rate of crashes and serious incidents related to HEMS in the United Kingdom.
      The aims of this article were to present data from a 26-year period since the
      start of HEMS operations in the United Kingdom and to compare them with published
      data from Germany, Australia, and the United States. Factors identified as
      affecting the safety of HEMS operations will also be discussed. METHODS: A PubMed
      search was performed to retrieve published data on accident rates and safety
      discussions for international HEMS using the key words HEMS, helicopter,
      emergency medical services, accident, incident, and crash. The details of every
      helicopter crash in the United States since the beginning of HEMS operations was
      obtained and reviewed to identify those that involved HEMS aircraft. This novel
      UK information was compared with published data from three international systems.
      RESULTS: A total of 13 accidents or serious incidents involving HEMS aircraft
      were identified from Civil Aviation Authority records, only 1 of which was a
      fatal accident. It was estimated that approximately 230,000 HEMS missions
      occurred in the United Kingdom between 1987 and 2013, giving an absolute accident
      incidence of approximately 0.0057% and a fatal accident incidence of
      approximately 0.00043%. The accident and fatal accident rate per 10,000 missions
      in the United Kingdom was 0.57 and 0.04, respectively. This compares with
      published rates from Germany, Australia, and the United States with accident rate
      per 10,000 missions ranging between 0.57 and 0.75 and fatal accident rates per
      10,000 missions ranging between 0.04 and 0.23. CONCLUSION: Accidents and serious
      incidents relating to HEMS operations in the United Kingdom have been
      comprehensively identified for the first time, allowing an estimation of overall
      accident and fatal accident rates and comparison with other countries' HEMS
      operations. Data collection and analysis were hampered by obscurity of data
      sources and poor availability of data. In a time of increasing HEMS use in the
      United Kingdom, it is essential to be mindful of safety, and standardization of
      data collection will improve focus in this important area.

PMID- 24662873
TI  - Stress hyperglycemia and surgical site infection in stable nondiabetic adults
      with orthopedic injuries.
AB  - BACKGROUND: Hyperglycemia in nondiabetic patients outside the intensive care unit
      is not well defined. We evaluated the relationship of hyperglycemia and surgical
      site infection (SSI) in stable nondiabetic patients with orthopedic injuries.
      METHODS: We conducted a prospective observational cohort study at a single
      academic Level 1 trauma center over 9 months (Level II evidence for
      therapeutic/care management). We included patients 18 years or older with
      operative orthopedic injuries and excluded patients with diabetes, corticosteroid
      use, multisystem injuries, or critical illness. Demographics, medical
      comorbidities (American Society of Anesthesiologists class), body mass index,
      open fractures, and number of operations were recorded. Fingerstick glucose
      values were obtained twice daily. Hyperglycemia was defined as a fasting glucose
      value greater than or equal to 125 mg/dL or a random value greater than or equal
      to 200 mg/dL on more than one occasion before the diagnosis of SSI. Glycosylated
      hemoglobin level was obtained from hyperglycemic patients; those with
      glycosylated hemoglobin level of 6.0 or greater were considered occult diabetic
      patients and were excluded. SSI was defined by a positive intraoperative culture
      at reoperation within 30 days of the index case. RESULTS: We enrolled 171
      patients. Of these 171, 40 (23.4%) were hyperglycemic; 7 of them were excluded
      for occult diabetes. Of the 164 remaining patients, 33 were hyperglycemic
      (20.1%), 50 had open fractures (6 Type I, 22 Type II, 22 Type III), and 12 (7.3%)
      had SSI. Hyperglycemic patients were more likely to develop SSI (7 of 33 [21.2%]
      vs. 5 of 131 [3.8%], p = 0.003). Open fractures were associated with SSI (7 of 50
      [14%] vs. 5 of 114 [4.4%], p = 0.047) but not hyperglycemia (10 of 50 [20.0%] vs.
      23 of 114 [20.2%], p = 0.98). There was no significant difference between
      infected and noninfected patients in terms of age, sex, race, American Society of
      Anesthesiologists class, obesity (body mass index > 29), tobacco use, or number
      of operations. CONCLUSION: Stress hyperglycemia was associated with SSI in this
      prospective observational cohort of stable nondiabetic patients with orthopedic
      injuries. Further prospective randomized studies are necessary to identify
      optimal treatment of hyperglycemia in the noncritically ill trauma population.
      LEVEL OF EVIDENCE: Therapeutic study, level III.

PMID- 24662872
TI  - Developing best practices to study trauma outcomes in large databases: an
      evidence-based approach to determine the best mortality risk adjustment model.
AB  - BACKGROUND: The National Trauma Data Bank (NTDB) is an invaluable resource to
      study trauma outcomes. Recent evidence suggests the existence of great
      variability in covariate handling and inclusion in multivariable analyses using
      NTDB, leading to differences in the quality of published studies and potentially
      in benchmarking trauma centers. Our objectives were to identify the best possible
      mortality risk adjustment model (RAM) and to define the minimum number of
      covariates required to adequately predict trauma mortality in the NTDB. METHODS:
      Analysis of NTDB 2009 was performed to identify the best RAM for trauma
      mortality. For each plausible NTDB covariate, univariate logistic regression was
      performed, and the area under the receiver operating characteristics curve
      (AUROC, with 95% confidence interval [CI]) was calculated. Covariates with p <
      0.01 and an AUROC of 0.6 of greater or with strong previous evidence were
      included in the subsequent multivariate logistic regression analyses. Manual
      backward selection was then used to identify the most parsimonious RAM with a
      similar AUROC (overlapping 95% CI). Similar analyses were performed for
      penetrating and severely injured patient subsets. All models were validated using
      NTDB 2010. RESULTS: A total of 630,307 patients from NTDB 2009 were analyzed. A
      total of 16 of 106 NTDB covariates tested on univariate analyses were selected
      for inclusion in the initial multivariate model. The best RAM included only six
      covariates (age, hypotension, pulse, total Glasgow Coma Scale [GCS] score, Injury
      Severity Score [ISS], and a need for ventilator use) yet still demonstrated
      excellent discrimination between survivors and nonsurvivors (AUROC, 0.9578; 95%
      CI, 0.9565-0.9590). In addition, this model was validated on 665,138 patients
      included in NTDB 2010 (AUROC, 0.9577; 95% CI, 0.9564-0.9589). Similar results
      were obtained for the subset analyses. CONCLUSION: This quantitative synthesis
      proposes a framework and a set of covariates for studying trauma mortality
      outcomes. Such analytic standardization may prove critical in implementing best
      practices aimed at improving the quality and consistency of NTDB-based research.
      LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 24662874
TI  - Potential prognostic factors predicting secondary amputation in third-degree open
      lower limb fractures.
AB  - BACKGROUND: With regard to the improved surgical possibilities and the rising
      tendency of attempted limb salvage, the topic of secondary amputation becomes
      increasingly important. The aim of this study was to identify potential
      prognostic factors predicting secondary amputation in third-degree open lower
      limb fractures. METHODS: All patients experienced third-degree open fractures of
      the lower limb without primary amputation (1994-2012). Prognostic factors were
      investigated to explain the final outcome of these patients (limb salvage vs.
      secondary amputation). RESULTS: From a total of 408 open diaphyseal tibia
      fractures, 93 consecutive fractures were identified (Gustilo-Anderson [G/A] type
      IIIA, n = 38; G/A type IIIB, n = 41; G/A type IIIC, n = 14) including seven
      patients with primary amputation. Definite limb salvage was achieved in 72
      patients (88%), whereas in 10 patients (12%), secondary amputation was necessary.
      The median time to secondary amputation was 12 days (range, 2-1,573 days). The
      median Injury Severity Score (ISS) was 11 (range, 9-41), and the median Mangled
      Extremity Severity Score (MESS) was 4 (range, 2-9). The MESS was significantly
      higher in the amputation group compared with the limb salvage group (p = 0.0001).
      Furthermore, statistical testing revealed that the amount of complex fractures (p
      = 0.0132), the soft tissue damage (p = 0.0050), the vascular injury rate (p =
      0.0110) and the fasciotomy rate (p = 0.0468) were significantly higher in the
      amputation group. In 60%, the limitations for limb salvage were infectious
      complications and/or, in 40%, was irreversible vessel occlusion after initial
      vessel reconstruction. CONCLUSION: The current study findings indicate that MESS
      is highly prognostic, but considering the significant advances in reconstructive
      techniques, decision making in patients with an MESS of 7 or greater should be
      reevaluated for the everyday clinical use. LEVEL OF EVIDENCE: Prognostic study,
      level III. Therapeutic study, level IV.

PMID- 24662875
TI  - Blood component transfusion increases the risk of death in children with
      traumatic brain injury.
AB  - BACKGROUND: Blood transfusion has been associated with worse outcomes in adult
      trauma patients with traumatic brain injury (TBI). However, the effects in
      injured children have not been evaluated. We hypothesize that blood transfusion
      is also associated with worse outcomes in children with TBI. METHODS: A
      retrospective review of the trauma database at two Level I pediatric trauma
      centers was performed. We reviewed all patients 18 years and younger with TBI,
      who survived at least 24 hours, from 2002 to 2011. Exclusion criteria include
      those who underwent craniotomy, thoracotomy, exploratory laparotomy, and any
      orthopedic procedure. RESULTS: A total of 1,607 children with TBI were included
      in the study population (mean age, 6.4 [5.7] years; 65% male), 178 of whom
      received a blood transfusion. Mean Injury Severity Score (ISS) was 16.5 (9.1).
      Patients who received a transfusion had a higher ISS than those who did not (26.7
      vs. 15.3). After controlling for age, sex, ISS, Glasgow Coma Scale (GCS) score on
      presentation, and mechanism of injury, patients who received a blood transfusion
      were more likely to be admitted to the intensive care unit (p < 0.0001), less
      likely to survive to hospital discharge (p = 0.02), more likely to be discharged
      to a rehabilitation facility (p = 0.01) and be dependent on caretakers at follow
      up (p < 0.0001), as well as more likely to develop urinary tract infection (p =
      0.02) and bacteremia (p = 0.02) during their hospital stay. These differences in
      outcomes among those who did and did not receive a blood transfusion began to
      disappear in patients with a nadir hemoglobin of less than 8.0 g/dL. CONCLUSION:
      Pediatric patients sustaining TBI who receive blood transfusion and do not
      require operative intervention have worse outcomes compared with patients who do
      not receive transfusion. This includes an increased risk of death. These data
      suggest that a transfusion trigger of hemoglobin level at 8.0 g/dL in injured
      children with TBI may be beneficial. LEVEL OF EVIDENCE: Epidemiologic study,
      level III. Therapeutic study, level IV.

PMID- 24662876
TI  - Management of children with mild traumatic brain injury and intracranial
      hemorrhage.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a significant public health problem
      affecting tens of thousands of children each year, and an important subset of
      these patients sustains intracranial hemorrhage (ICH). The purpose of this study
      was to test the hypothesis that we could identify a subset of children with
      traumatic ICH who could be monitored on a general neurosurgery ward with a low
      risk of clinical deterioration. METHODS: We performed a retrospective review of
      pediatric patients 18 years or younger with mild TBI (Glasgow Coma Scale [GCS]
      score 14-15) and traumatic ICH admitted to Saint Louis Children's Hospital
      between 2006 and 2011. We excluded patients with injuries unrelated to the TBI
      that would require intensive care unit (ICU) admission and those with penetrating
      intracranial injuries. RESULTS: We identified 118 patients meeting inclusion
      criteria. Repeat neuroimaging was obtained in 69 (58%) of 118 patients.
      Radiologic progression was noted in 6 (8.7%) of 69 patients, with a trend toward
      more frequent progression in patients with epidural hematoma (EDH) versus other
      ICH (3 [20%] of 15 vs. 3 [5.6%] of 54; p = 0.11). Of 118 patients, 8 (6.8%)
      experienced clinically important neurologic decline (CIND) and 6 (5.1%) required
      neurosurgical intervention. Both CIND and the need for neurosurgical intervention
      were significantly higher in patients with EDH (21% each) compared with those
      with other types of ICH (4% and 2%, respectively) (p = 0.02, p < 0.01). Based on
      these results, we developed a preliminary management framework to assist in
      determining which patients can be safely observed on a neurosurgery ward without
      an ICU admission. Specifically, those patients without EDH, intraventricular
      hemorrhage, coagulopathy, or concern for a high-risk neurosurgical lesion (e.g.,
      arteriovenous malformation) may be safely observed on the ward. CONCLUSIONS:
      These results demonstrate that few children with mild TBI and ICH experience CIND
      and the preliminary framework we developed assists in identifying which patients
      can safely avoid ICU admission. This framework should be validated prospectively
      and externally. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

PMID- 24662877
TI  - There's no place like home: boarding surgical ICU patients in other ICUs and the
      effect of distances from the home unit.
AB  - BACKGROUND: Intensive care units (ICUs) function frequently at capacity,
      requiring incoming critically ill patients to be placed in alternate
      geographically distinct ICUs. In some medical ICU populations, "boarding" in an
      overflow ICU has been associated with increased mortality. We hypothesized that
      surgical ICU patients experience more complications when boarding in an overflow
      ICU and that the frequency of these complications are greatest in boarders
      farthest from the home unit (HU). METHODS: A 5-year (June 2005 to June 2010)
      retrospective review of a prospectively maintained ICU database was performed,
      and demographics, severity of illness, length of stay, and incidence of ICU
      complications were extracted. Distances between boarding patients' rooms and the
      HU were measured. Complications occurring in patients located in the same floor
      (BUSF) and different floor (BUDF) boarding units were compared and stratified by
      distance from HU to the patient room. Logistic regression was used to develop
      control for known confounders. RESULTS: A total of 7,793 patients were admitted
      to the HU and 833 to a boarding unit (BUSF, n = 712; BUDF, n = 121). Boarders
      were younger, had a lower length of stay, and Acute Physiology and Chronic Health
      Evaluation II and were more often trauma/emergency surgery patients. Compared
      with in-HU patients, the incidence of aspiration pneumonia (2.2% vs. 3.6%, p <
      0.01) was greater in BUSF patients and highest in those farthest from the HU
      (odds ratio [OR], 2.39; p = 0.01). Delirium occurred less often in HU than in
      BUDF patients (3.3% vs. 8.3 %, p < 0.01), and both delirium (OR, 6.09, p < 0.01)
      and ventilator-associated pneumonia (OR, 4.49, p < 0.05) were more frequent in
      patients farther from the HU. CONCLUSION: Certain ICU complications occur more
      frequently in boarding patients particularly if they are located on a different
      floor or far from the HU. When surgical ICU bed availability forces overflow
      admissions to non-home ICUs, greater interdisciplinary awareness, education, and
      training may be needed to ensure equivalent care and outcomes. LEVEL OF EVIDENCE:
      Epidemiologic study, level III. Therapeutic study, level IV.

PMID- 24662878
TI  - A community traffic safety analysis of pedestrian and bicyclist injuries based on
      the catchment area of a trauma center.
AB  - BACKGROUND: This study was designed to examine the characteristics of pedestrian
      and bicyclist collisions with motor vehicles within New York City's high-density
      hub. The primary objectives were to map crash locations and to identify hot spots
      within these injury clusters. The secondary objective was to quantify differences
      in injury severity based on road type and user behaviors. METHODS: Between
      December 2008 and June 2011, data were prospectively collected from pedestrians
      and bicyclists struck by motor vehicles and brought to Bellevue Hospital, a Level
      1 trauma center in New York City. Behaviors by cohort (i.e., crossing patterns
      for pedestrians, riding patterns for bicyclists), Injury Severity Score (ISS),
      and collision locations were extracted from the database. Analyses of mean ISS
      were performed using a Student's t test with a p < 0.05 considered significant.
      Geomaps were created to identify clusters or "hot spots," where higher volumes of
      crashes occurred over time. Spatial analysis was performed to demonstrate whether
      these were random events. RESULTS: A total of 1,457 patients (1,075 pedestrians
      and 382 bicyclists) were enrolled. Collision locations were known for 97.5%. Of
      the injured pedestrians, those crossing avenues (n = 277) had higher ISSs than
      those crossing streets (n = 522) (p = 0.01) and were more likely to die (p =
      0.002). Pedestrians crossing midblock (n = 185) had higher mean ISSs than those
      crossing with the signal in the crosswalk (n = 320) (8.12 vs. 5.01, p < 0.001).
      Based on density mapping, hot spots of pedestrian collisions were detected in
      midtown Manhattan, while hot spots for bicyclists were detected at bridge and
      tunnel portals. Spatial analysis indicates that these are not random events (p <
      0.05). CONCLUSION: Pedestrians injured on avenues sustained more serious injuries
      than those injured on narrower streets. A better understanding of collision
      locations and features may allow for tailored injury prevention strategies.
      Trauma centers serve an important role in public health surveillance within their
      local communities. LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 24662879
TI  - Shock index predicts mortality in geriatric trauma patients: an analysis of the
      National Trauma Data Bank.
AB  - BACKGROUND: Heart rate and systolic blood pressure are unreliable in geriatric
      trauma patients. Shock index (SI) (heart rate/systolic blood pressure) is a
      simple marker of worse outcomes after injury. The aim of this study was to assess
      the utility of SI in predicting outcomes. We hypothesized that SI predicts
      mortality in geriatric trauma patients. METHODS: We performed a 4-year (2007
      2010) retrospective analysis using the National Trauma Data Bank. Patients 65
      years or older were included. Transferred patients, patients dead on arrival,
      missing vitals on presentation, and patients with burns and traumatic brain
      injury were excluded. A cutoff value of SI greater than or equal to 1
      (sensitivity, 81%; specificity, 79%) was used to define hemodynamic instability.
      The primary outcome measure was mortality. Secondary outcome measures were need
      for blood transfusion, need for exploratory laparotomy, and development of in
      hospital complications. Multiple logistic regressions were performed. RESULTS: A
      total of 485,595 geriatric patients were reviewed, of whom 217,190 were included.
      The mean (SD) age was 77.7 (7.1) years, 60% were males, median Glasgow Coma Scale
      (GCS) score was 14 (range, 3-15), median Injury Severity Score (ISS) was 9
      (range, 4-18), and mean (SD) SI was 0.58 (0.18). Three percent (n = 6,585) had an
      SI greater than or equal to 1. Patients with SI greater than or equal to 1 were
      more likely to require blood product requirement (p = 0.001), require an
      exploratory laparotomy (p = 0.01), and have in-hospital complications (p = 0.02).
      The overall mortality rate was 4.1% (n = 8,952). SI greater than or equal to 1
      was the strongest predictor for mortality (odds ratio, 3.1; 95% confidence
      interval, 2.6-3.3; p = 0.001) in geriatric trauma patients. Systolic blood
      pressure (p = 0.09) and heart rate (p = 0.2) were not predictive of mortality.
      CONCLUSION: SI is an accurate and specific predictor of morbidity and mortality
      in geriatric trauma patients. SI is superior to heart rate and systolic blood
      pressure for predicting mortality in geriatric trauma patients. Geriatric trauma
      patients with SI greater than or equal to 1 should be transferred to a Level 1
      trauma center. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

PMID- 24662880
TI  - Obesity and vehicle type as risk factors for injury caused by motor vehicle
      collision.
AB  - BACKGROUND: This study sought to describe variations in the risk of motor vehicle
      collision (MVC) injury and death by occupant body mass index (BMI) class and
      vehicle type. We hypothesized that the relationship between BMI and the risk of
      MVC injury or mortality would be modified by vehicle type. METHODS: This is a
      retrospective cohort study of occupants involved in MVCs using data from the
      Crash Injury Research and Engineering Network and the National Automotive
      Sampling System Crashworthiness Data System. Occupants were grouped based on
      vehicle body style (passenger car, sport utility vehicle, or light truck) and
      vehicle size (compact or normal, corresponding to below- or above-average curb
      weight). The relationship between occupant BMI class (underweight, normal weight,
      overweight, or obese) and risk of injury or mortality was examined for each
      vehicle type. Odds ratios (ORs) adjusted for various occupant and collision
      characteristics were estimated. RESULTS: Of an estimated 44 million occupants of
      MVCs sampled from 2000 to 2009, 37.1% sustained an injury. We limited our
      analysis to injuries achieving an Abbreviated Injury Scale (AIS) score of 2 or
      more severe, totaling 17 million injuries. Occupants differed substantially in
      terms of demographic and collision characteristics. After adjustment for
      confounding factors, we found that obesity was a risk factor for mortality caused
      by MVC (OR, 1.6; 95% confidence interval [CI], 1.2-2.0). When stratified by
      vehicle type, we found that obesity was a risk factor for mortality in larger
      vehicles, including any-sized light trucks (OR, 2.1; 95% CI, 1.3-3.5), normal
      sized passenger cars (OR, 1.6; 95% CI, 1.1-2.3), and normal-sized sports utility
      vehicles or vans (OR, 2.0; 95% CI, 1.0-3.8). Being overweight was a risk factor
      in any-sized light trucks (OR, 1.5; 95% CI, 1.1-2.1). CONCLUSION: We identified a
      significant interaction between occupant BMI class and vehicle type in terms of
      MVC-related mortality risk. Both factors should be taken into account when
      considering occupant safety, and additional study is needed to determine
      underlying causes of the observed relationships. LEVEL OF EVIDENCE: Epidemiologic
      study, level III.

PMID- 24662881
TI  - Systematic review of the benefits and harms of whole-body computed tomography in
      the early management of multitrauma patients: are we getting the whole picture?
AB  - BACKGROUND: There is considerable interest in whether routine whole-body computed
      tomography (WBCT) imaging produces different patient outcomes in blunt trauma
      patients when compared with selective imaging. This article aimed to
      systematically review the literature for all outcomes measured in comparing WBCT
      with selective imaging in trauma patients and to evaluate the comprehensiveness
      of relevant dimensions for this comparison. METHODS: We performed a systematic
      review of studies comparing WBCT and selective imaging approaches during the
      initial assessment of multitrauma patients. Peer-reviewed studies including
      cohort studies, randomized controlled trials, meta-analyses, and systematic
      reviews were identified through large database searches and filtered through
      methodologic inclusion criteria. Data on study characteristics, hypotheses and
      conclusions made, outcomes assessed, and references to potential benefits and
      harms were extracted. RESULTS: Eight retrospective cohort studies and two
      systematic reviews were identified. Six primary studies evaluated mortality as an
      outcome, and four studies found a significant difference in results favoring WBCT
      imaging over selective imaging. All five articles assessing various time
      intervals in hospital following imaging after injury found significantly reduced
      times with WBCT. Radiation exposure was found to be increased after WBCT imaging
      compared with selective imaging in the only study in which it was evaluated. The
      two systematic reviews analyzed the same three articles with regard to mortality
      but concluded differently about overall benefits. CONCLUSION: WBCT imaging seems
      to be associated with reduced times to events in hospital following traumatic
      injury and seems to be associated with decreased mortality. Whether this is a
      true effect mediated through an as yet unsubstantiated change in management or
      the result of hospital- or individual-level confounders is unclear. When
      evaluating these outcomes, it seems that the authors of both primary studies and
      systematic reviews have often been selective in their choice of short-term
      outcomes, painting an incomplete picture of the issue. LEVEL OF EVIDENCE:
      Systematic review, level III.

PMID- 24662882
TI  - Pressure ulcers from spinal immobilization in trauma patients: a systematic
      review.
AB  - BACKGROUND: To protect the (possibly) injured spine, trauma patients are
      immobilized on backboard or vacuum mattress, with a cervical collar, lateral
      headblocks, and straps. Several studies identified pressure ulcer (PU)
      development from these devices. The aim of this literature study was to gain
      insight into the occurrence and development of PUs, the risk factors, and the
      possible interventions to prevent PUs related to spinal immobilization with
      devices in adult trauma patients. METHODS: We systematically searched PubMed
      (MEDLINE), EMBASE, Cochrane, and CINAHL for the period 1970 to September 2011.
      Studies were included if participants were healthy volunteers under spinal
      immobilization or trauma patients under spinal immobilization until spine
      injuries were diagnosed or excluded. Outcomes of primary interest included
      occurrence, severity, and risk for PU development as well as prevention of PU
      development related to spinal immobilization devices. RESULTS: The results of
      included studies show an incidence of collar-related PUs ranging from 6.8% to
      38%. Described locations are the occiput, chin, shoulders, and back. The severity
      of these PUs varies between Stages 1 and 3, and one study describes PUs requiring
      surgical debridement, indicating a Stage 4 PU. Described risk factors for PU
      development are high pressure and pain from immobilizing devices, the length of
      time in/on a device, intensive care unit admission, high Injury Severity Scores
      (ISSs), mechanical ventilation, and intracranial pressure monitoring. Preventive
      interventions for collar-related PUs include early replacement of the extrication
      collar and regular skin assessment, collar refit, and position change.
      CONCLUSION: The results from this systematic review show that immobilization with
      devices increases the risk for PU development. This risk is demonstrated in nine
      experimental studies with healthy volunteers and in four clinical studies. LEVEL
      OF EVIDENCE: Systematic review, level III.

PMID- 24662883
TI  - Current views on acute to chronic pain transition in post-traumatic patients:
      risk factors and potential for pre-emptive treatments.

PMID- 24662884
TI  - Frailty in surgery.

PMID- 24662885
TI  - A consensus-based criterion standard for trauma center need.
AB  - BACKGROUND: In civilian trauma care, field triage is the process applied by
      prehospital care providers to identify patients who are likely to have severe
      injuries and immediately need the resources of a trauma center. Studies of the
      efficacy of field triage have used various measures to define trauma center need
      because no "criterion standard" exists, making cross-study comparisons difficult.
      This study aimed to develop a consensus-based functional criterion standard
      definition of trauma center need. METHODS: Local and national experts were
      recruited for participation. Blinded key informant interviews were conducted in
      order of availability until no new themes emerged. Themes identified during the
      interviews were used to develop a Modified Delphi survey, which was
      electronically delivered via Survey Monkey. The trauma center need criteria were
      refined iteratively based on participant responses. Participants completed
      additional surveys until there was at least 80% agreement for each criterion.
      RESULTS: Fourteen experts were recruited. Five participated in key informant
      interviews. A Modified Delphi survey was administered five times (four
      modifications based on the expert's responses). After the fifth round, there was
      at least 82% agreement on each criterion. The final definition included 10 time
      specific indicators: major surgery, advanced airway, blood products, admission
      for spinal cord injury, thoracotomy, pericardiocentesis, cesarean delivery,
      intracranial pressure monitoring, interventional radiology, and in-hospital
      death. CONCLUSION: We developed a consensus-based functional criterion standard
      definition of needing the resources of a trauma center, which may help to
      standardize field triage research and quality assurance in trauma systems as well
      as allow for cross study comparisons.

PMID- 24662888
TI  - Well-being losses due to care-giving.
AB  - This paper estimates the impact of informal caregiving on self-reported well
      being. It uses a sample of 23,285 respondents of the first eleven waves of the
      Household, Income and Labour Dynamics in Australia (HILDA). We apply a relatively
      new analytical method that enables us to estimate fixed effects ordered logit to
      analyse subjective well-being. The econometric estimates show that providing
      informal care has a negative effect on subjective well-being. The empirical
      evidence of our paper could be helpful to inform policy makers to better
      understand the impact of caregiving and design the appropriate long term care
      policies and support services. 

PMID- 24662889
TI  - Early Clostridium difficile infection during allogeneic hematopoietic stem cell
      transplantation.
AB  - Clostridium difficile infection (CDI) is frequently diagnosed in recipients of
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). We characterized
      early-transplant CDI and its associations, and analyzed serially-collected feces
      to determine intestinal carriage of toxigenic C. difficile. Fecal specimens were
      collected longitudinally from 94 patients during allo-HSCT hospitalization, from
      the start of pre-transplant conditioning until up to 35 days after stem cell
      infusion. Presence of C. difficile 16S rRNA and tcdB genes was determined.
      Clinical variables and specimen data were analyzed for association with
      development of CDI. Historical data from an additional 1144 allo-HSCT patients
      was also used. Fecal specimens from 37 patients (39%) were found to harbor C.
      difficile. Early-transplant CDI was diagnosed in 16 of 94 (17%) patients
      undergoing allo-HSCT; cases were generally mild and resembled non-CDI diarrhea
      associated with transplant conditioning. CDI was associated with preceding
      colonization with tcdB-positive C. difficile and conditioning regimen intensity.
      We found no associations between early-transplant CDI and graft-versus-host
      disease or CDI later in transplant. CDI occurs with high frequency during the
      early phase of allo-HSCT, where recipients are pre-colonized with toxigenic C.
      difficile. During this time, CDI incidence peaks during pre-transplant
      conditioning, and is correlated to intensity of the treatment. In this unique
      setting, high rates of CDI may be explained by prior colonization and
      chemotherapy; however, cases were generally mild and resembled non-infectious
      diarrhea due to conditioning, raising concerns of misdiagnosis. Further study of
      this unique population with more discriminating CDI diagnostic tests are
      warranted. 

PMID- 24662890
TI  - Endothelial microparticles and endothelial damage: 'the tip and the iceberg'.

PMID- 24662891
TI  - MCM10: one tool for all-Integrity, maintenance and damage control.
AB  - Minichromsome maintenance protein 10 (Mcm10) is an essential replication factor
      that is required for the activation of the Cdc45:Mcm2-7:GINS helicase. Mcm10's
      ability to bind both ds and ssDNA appears vital for this function. In addition,
      Mcm10 interacts with multiple players at the replication fork, including DNA
      polymerase-alpha and proliferating cell nuclear antigen with which it cooperates
      during DNA elongation. Mcm10 lacks enzymatic function, but instead provides the
      replication apparatus with an oligomeric scaffold that likely acts in the
      coordination of DNA unwinding and DNA synthesis. Not surprisingly, loss of Mcm10
      engages checkpoint, DNA repair and SUMO-dependent rescue pathways that
      collectively counteract replication stress and chromosome breakage. Here, we
      review Mcm10's structure and function and explain how it contributes to the
      maintenance of genome integrity. 

PMID- 24662892
TI  - Nuclear matrix, nuclear envelope and premature aging syndromes in a translational
      research perspective.
AB  - Lamin A-related progeroid syndromes are genetically determined, extremely rare
      and severe. In the past ten years, our knowledge and perspectives for these
      diseases has widely progressed, through the progressive dissection of their
      pathophysiological mechanisms leading to precocious and accelerated aging, from
      the genes mutations discovery until therapeutic trials in affected children. A
      type lamins are major actors in several structural and functional activities at
      the nuclear periphery, as they are major components of the nuclear lamina.
      However, while this is usually poorly considered, they also play a key role
      within the rest of the nucleoplasm, whose defects are related to cell senescence.
      Although nuclear shape and nuclear envelope deformities are obvious and visible
      events, nuclear matrix disorganization and abnormal composition certainly
      represent the most important causes of cell defects with dramatic pathological
      consequences. Therefore, lamin-associated diseases should be better referred as
      laminopathies instead of envelopathies, this later being too restrictive,
      considering neither the key structural and functional roles of soluble lamins in
      the entire nucleoplasm, nor the nuclear matrix contribution to the
      pathophysiology of lamin-associated disorders and in particular in defective
      lamin A processing-associated aging diseases. Based on both our understanding of
      pathophysiological mechanisms and the biological and clinical consequences of
      progeria and related diseases, therapeutic trials have been conducted in patients
      and were terminated less than 10 years after the gene discovery, a quite fast
      issue for a genetic disease. Pharmacological drugs have been repurposed and used
      to decrease the toxicity of the accumulated, unprocessed and truncated prelaminA
      in progeria. To date, none of them may be considered as a cure for progeria and
      these clinical strategies were essentially designed toward reducing a subset of
      the most dramatic and morbid features associated to progeria. New therapeutic
      strategies under study, in particular targeting the protein expression pathway at
      the mRNA level, have shown a remarkable efficacy both in vitro in cells and in
      vivo in mice models. Strategies intending to clear the toxic accumulated proteins
      from the nucleus are also under evaluation. However, although exceedingly rare,
      improving our knowledge of genetic progeroid syndromes and searching for
      innovative and efficient therapies in these syndromes is of paramount importance
      as, even before they can be used to save lives, they may significantly (i) expand
      the affected childrens' lifespan and preserve their quality of life; (ii) improve
      our understanding of aging-related disorders and other more common diseases; and
      (iii) expand our fundamental knowledge of physiological aging and its links with
      major physiological processes such as those involved in oncogenesis. 

PMID- 24662893
TI  - Tube fusion: making connections in branched tubular networks.
AB  - Organs like the vertebrate vascular system and the insect tracheal system develop
      from separate primordia that undergo fusion events to form interconnected tubular
      networks. Although the correct pattern of tubular connections (anastomoses) in
      these organs is crucial for their normal function, the cellular and molecular
      mechanisms that govern tube fusion are only beginning to be understood. The
      process of tube fusion involves tip cell specification, cell-cell recognition and
      contact formation, self-avoidance, changes in cell shape and topology, lumen
      formation, and luminal membrane fusion. Significant insights into the underlying
      cellular machinery have been provided by genetic studies of tracheal tube fusion
      in Drosophila. Here, we summarize these findings and we highlight similarities
      and differences between tube fusion processes in the Drosophila tracheae and in
      the vertebrate vascular system. We integrate the findings from studies in vivo
      with the important mechanistic insights that have been gained from the analysis
      of tubulogenesis in cultured cells to propose a mechanistic model of tube fusion,
      aspects of which are likely to apply to diverse organs and organisms. 

PMID- 24662894
TI  - Environmental influences on physical activity in rural Midwestern adults: a
      qualitative approach.
AB  - Qualitative research can be used to examine multiple factors associated with
      physical activity and help practitioners identify language used by the rural
      adult population when discussing this behavior. Three focus groups were conducted
      among 19 residents of multiple towns in a rural Midwestern county to examine the
      language and influences on rural physical activity. Focus group members were
      asked to define physical activity, exercise, community, and neighborhood. They
      were asked about the activities they engaged in and facilitators and barriers to
      those activities. A guidebook was developed to capture major themes and common
      patterns that emerged in the responses to the topics discussed. The data were
      reviewed for repeated statements and points that were agreed on by multiple
      participants. Important factors associated with physical activity include the
      importance of social support and modeling physical activity behavior. Also, the
      influence of pets and children was important for engaging these adults in
      physical activity. The focus group members engaged in walking and bicycling in
      their neighborhood streets and community trails, and desired to see community
      buildings be open to the public for exercise. This study revealed contextual
      issues and culturally relevant language for practitioners to use in tailoring
      physical activity measurement tools or designing interventions for a rural adult
      population. Social support (specifically, seeing others being active and using
      pets as motivators for being active) and policy attitudes may be targeted for
      interventions to increase physical activity in rural adults. 

PMID- 24662895
TI  - Longer term impact of the mass media campaign to promote the Get Healthy
      Information and Coaching Service(r): increasing the saliency of a new public
      health program.
AB  - The Get Healthy Information and Coaching Service(r) (GHS) was introduced in New
      South Wales in February 2009. It used mass reach media advertising and direct
      mail and/or proactive marketing to recruit participants. This article reports on
      the long-term impact of the campaign on GHS participation from July 2011 to June
      2012. A stand-alone population survey collected awareness, knowledge, and
      behavioral variables before the first advertising phase, (n = 1,544, August
      September 2010), during the advertising period (n = 1,500, February-March 2011; n
      = 1,500, June-July 2011; n = 1,500, February 2012), and after the advertising
      period (n = 1,500, June-July 2012). GHS usage data (n = 6,095) were collated
      during July 2011-June 2012. Unprompted and prompted awareness of GHS mass media
      significantly increased (0% to 8.0%, p < .001; and 14.1% to 43.9%, p < .001,
      respectively) as well as knowledge and perceived effectiveness of the GHS. Those
      from the lowest three quintiles of socioeconomic disadvantage and respondents who
      were overweight or obese were significantly more likely to report prompted
      campaign awareness. The majority (84.4%) of new GHS calls occurred when
      television advertising was present. Participants who cited mass media as their
      referral source were significantly more likely to enroll in the intensive
      coaching program. Mass media campaigns remain an effective method of promoting a
      telephone-based statewide lifestyle program. 

PMID- 24662896
TI  - Effect of a child care center-based obesity prevention program on body mass index
      and nutrition practices among preschool-aged children.
AB  - This study examined the effect of an early childhood obesity prevention program
      on changes in Body Mass Index (BMI) z-score and nutrition practices. Eight child
      care centers were randomly assigned to an intervention or attention control arm.
      Participants were a multiethnic sample of children aged 2 to 5 years old (N =
      307). Intervention centers received healthy menu changes and family-based
      education focused on increased physical activity and fresh produce intake,
      decreased intake of simple carbohydrate snacks, and decreased screen time.
      Control centers received an attention control program. Height, weight, and
      nutrition data were collected at baseline and at 3, 6, and 12 months. Analysis
      examined height, weight, and BMI z-score change by intervention condition (at
      baseline and at 3, 6, and 12 months). Pearson correlation analysis examined
      relationships among BMI z-scores and home activities and nutrition patterns in
      the intervention group. Child BMI z-score was significantly negatively correlated
      with the number of home activities completed at 6-month post intervention among
      intervention participants. Similarly, intervention children consumed less junk
      food, ate more fresh fruits and vegetables, drank less juice, and drank more 1%
      milk compared to children at control sites at 6 months post baseline. Ninety
      seven percent of those children who were normal weight at baseline were still
      normal weight 12 months later. Findings support child care centers as a promising
      setting to implement childhood obesity prevention programs in this age group. 

PMID- 24662897
TI  - Erasing epilepsy stigma: eight key messages.
AB  - Historically, epilepsy has been ignored by the public health community, despite
      the fact that there are more than 2 million people with epilepsy in the United
      States. Although epilepsy affects 1 in 26 people during their lifetime, the
      general public lacks basic knowledge and holds misperceptions about epilepsy that
      contribute to its associated stigma. Consequently, people with epilepsy continue
      to fare poorly, with lower physical, mental, and social well-being. Recently, the
      2012 Institute of Medicine (IOM) report Epilepsy Across the Spectrum: Promoting
      Health and Understanding inspired a new sense of enthusiasm in the epilepsy
      community that can serve as a catalyst to change public perceptions about
      epilepsy. To erase stigma, the IOM committee made recommendations in two areas:
      (a) informing the media and (b) coordinating public awareness. The committee also
      identified eight key messages about epilepsy that the public should know. Health
      promotion and education professionals can play a critical role in disseminating
      these messages to the general public in their local communities and supporting
      interventions and policies to change the face of epilepsy. 

PMID- 24662898
TI  - An empirical case study of the effects of training and technical assistance on
      community coalition functioning and sustainability.
AB  - The case study analyzes the effects of training and technical assistance on the
      amount of community changes facilitated by members of a community coalition to
      prevent adolescent substance use. The study examines the sustainability of these
      changes in the community over time. The coalition implemented a Community Change
      Intervention that focused on building coalition capacity to support
      implementation of community changes-program, policy, and practice changes. Over
      the 2-year intervention period, there were 36 community changes facilitated by
      the coalition to reduce risk for adolescent substance use. Results showed that
      the coalition facilitated an average of at least 3 times as many community
      changes (i.e., program, policy and practice changes) per month following the
      intervention. Action planning was found to have accelerated the rate of community
      changes implemented by the coalition. After the intervention there was increased
      implementation of three key prioritized coalition processes: Documenting
      Progress/Using Feedback, Making Outcomes Matter, and Sustaining the Work. A 1
      year probe following the study showed that the majority of the community changes
      were sustained. Factors associated with the sustainability of changes included
      the continued development of collaborative partnerships and securing multiyear
      funding. 

PMID- 24662900
TI  - The role of selected variables in the diagnosis of cervical derangement
      syndromes.
AB  - BACKGROUND: The study analyzed correlations between selected variables in
      cervical derangement syndromes. MATERIAL AND METHODS: We analyzed data from 63
      patients regarding pain (VAS, McGill Pain Questionnaire), mobility (CROM
      goniometer), dizziness, nausea, the duration of the current episode, and the
      number of previous episodes (history). Student's t and chi(2) tests and Pearson's
      r correlation were used. RESULTS: Overall pain intensity correlated positively
      with the indexes of the McGill Pain Questionnaire, the duration of the current
      episode, intensity of the proximal and distal symptoms and negatively with
      protraction or extension. Headache correlated positively with neck pain and
      negatively with retraction. Neck pain cor-related negatively with multiple
      cervical movements and positively with intensity of the distal symptoms. A
      positive relationship between shoulder and upper limb pain was observed. Patients
      with higher overall pain intensity or lower shoulder pain intensity experienced
      dizziness more often. The duration of the current episode correlated positively
      with the number of previous episodes, the frequency of nausea, limited extension
      and limited protraction. Nausea coexisted with dizziness and reduced protraction.
      The degree of flexion restriction correlated positively with the number of
      previous episodes. CONCLUSIONS: 1. Overall and proximal pain intensity, mobility
      of the cervical spine, the duration of the current episode and dizziness are
      useful in diagnosis of cervical derangement syndromes. 2. Intensity of the distal
      symptoms, the number of previous episodes and nausea should be particularly
      monitored.

PMID- 24662899
TI  - Venous thromboembolism prophylaxis in arthroscopic surgery.
AB  - The prophylaxis and epidemiology of venous thromboembolism (VTE) following major
      orthopaedic procedures has been widely discussed in the world literature.
      Significantly less attention in the recent years has been paid to antithrombotic
      prophylaxis following arthroscopic procedures. In the past few years numerous
      controversies have developed as a result of contradictory guidelines advocated by
      various centres. Clinical studies involving prospective patient groups result in
      guidelines being published by orthopaedic associations. The guidelines issued by
      the Ame-rican College of Chest Physicians (ACCP) are the most influential. The
      latest edition of the guidelines was published in 2012. The National Institute
      for Health and Clinical Excellence (NICE) is a British centre which issues
      guidelines for antithrombotic prophylaxis. The latest version of the guidelines
      is the Clinical Guidelines (CG) 92, dated 2010. Polish guidelines were developed
      by a working group headed by Prof. Krystyna Zawilska. The Polish Society of
      Orthopaedics and Traumatology (PSOT) has not endorsed or recommended the
      guidelines put forward by the Working Group in 2012, so the PSOT guidelines are
      valid regarding orthopaedics and arthroscopic procedures. The comparison of
      international and Polish guidelines indicates a considerable discrepancy between
      the approaches to antithrombotic prophylaxis in arthroscopic procedures. From the
      viewpoint of an orthopaedist it is most important to select a prophylactic
      procedure appropriate for a specific patient. It is necessary to explain the need
      of prophylaxis to the patient, assess the risk factors of thrombosis and employ
      reliable tools, such as Wells' score. Pharmacological prophylaxis is well-known
      and widely used in arthroscopic procedures in Polish centres. However, it is also
      important to implement mechanical prophylactic measures, which are neglected or
      used to a limited extent in numerous centres. In recent years, American
      researchers conducted studies of large groups of patients with regard to the
      prophylaxis and incidence of VTE following arthroscopic procedures of the knee,
      hip and shoulder. The incidence of VTE following knee, hip and shoulder
      arthroscopy was 0.42%, 3.7% and 0.31%, respectively. The findings of the study
      support the validity of the guidelines issued by the American College of Chest
      Physicians in 2012. 

PMID- 24662901
TI  - The influence of generalized joint hypermobility on the sagittal profile of the
      spine in children aged 10-13 years.
AB  - BACKGROUND: Children commonly attend exercise programs to correct abnormal
      sagittal curvatures of the spine. The presence of generalized joint hypermobility
      (JH) is often disregarded during exercise planning. The aim of the study was to
      assess the influence of JH on the sagittal curvatures of the spine. MATERIAL AND
      METHODS: The JH group included 38 girls and 37 boys aged 10-13 years with known
      JH (Beighton test cut-off >= 5 points for girls, and >= 4 for boys). A control
      group included 197 girls and 150 boys. The children were matched for age, height,
      weight and BMI. The sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis
      (TK), distal thoracic kyphosis (DK), and proximal thoracic kyphosis (PK) were
      assessed with a Saunders inclinometer. The results in children with and without
      JH were compared. RESULTS: There were no significant (p>0.05) differences between
      girls with and without JH with respect to SS (22.5 degrees  +/- 9.9 vs 23.0
      degrees  +/- 8.0), LL (31.0 degrees  +/- 14.0 vs 33.0 degrees  +/- 10.0), TK
      (39.0 degrees  +/- 10.4 vs 39.6 degrees  +/- 10.0), DK (8.7 degrees  +/- 6.9 vs
      7.9 degrees  +/- 7.8) or PK (31.3 degrees  +/- 7.1 vs 32.3 degrees  +/- 7.3). The
      differences among boys were similarly non-significant (p>0.05) (19.0 degrees  +/-
      7.9 vs 19.7 degrees  +/- 6.6; 30.6 degrees  +/- 9.0 vs 31.9 degrees  +/- 8.4;
      42.7 degrees  +/- 8.0 vs 40.6 degrees  +/- 8.7; 9.7 degrees  +/- 7.9 vs 8.2
      degrees  +/- 7.8; 33.7 degrees  +/- 5,0 vs 32.8 degrees  +/- 7.0, for SS, LL, TK,
      DK and PK, respectively). CONCLUSIONS: 1. The sagittal profile of the spine did
      not differ between children with and without JH, which may lead to suboptimal
      exercise plans. 2. The routine examination of the musculoskeletal system should
      be extended to include an assessment of JH.

PMID- 24662902
TI  - Impact of knee arthroplasty on knee sensorimotor system performance.
AB  - BACKGROUND: The study aimed to assess the impact of joint degeneration due to
      advanced gonarthrosis and the effect of arthroplasty on proprioception and
      sensorimotor system performance of the knee. MATERIAL AND METHOD: The
      arthroplasty group comprised 62 persons, aged 68.8 years on average, who
      underwent knee replacement due to gonarthrosis. The control group consisted of 74
      healthy persons, with an average age of 67.5 years. The participants performed a
      test of Joint Position Sense (JPS) at 45 degrees  flexion and a Sensorimotor
      Control Test (SCT) designed by the authors to evaluate sensorimotor system
      performance (on a scale of 0-5). The arthroplasty group was assessed three times:
      before the knee replacement surgery, and then at 8 and 100 days after the
      surgery. The control group was assessed once. RESULTS: The control group scored a
      mean of 4.9 in the SCT test and 3.9 degrees  in the JPS test. The mean scores
      upon consecutive measurements in the arthroplasty group were 3.1, 2.9 and 4.5 for
      the SCT test and 10.5 degrees , 9.5 degrees  and 3.9 degrees  (compared to 8.1
      degrees  for the healthy limb) for the JPS test. CONCLUSIONS: 1. Considerable
      proprioceptive and sensorimotor system performance deficits, as recorded in the
      arthroplasty group, may contribute to faster progression of degenerative disease
      and increase the risk of a fall. 2. The Sensorimotor Control Test designed by the
      authors seems to represent an objective and comprehensive method for assessing
      the sensorimotor system performance of the knee in gonarthrosis patients. 3. The
      Sensorimotor Control Test provides a qualitative assessment and may be employed
      in the clinical therapeutic setting.

PMID- 24662903
TI  - Postural stability in patients with osteoarthritis of the hip. Pilot study.
AB  - BACKGROUND: Total hip arthroplasty involves division of the joint capsule, which
      can cause receptor damage, affecting postural stability and increasing the risk
      of falls. The aim of this study was to determine whether postural stability can
      be disturbed by total hip arthroplasty from a postero-lateral approach. MATERIAL
      AND METHODS: Static balance was quantified with the use of a two plate
      tensometric platform in a study group of 16 patients (8 women and 8 men) with
      unilateral hip osteoarthritis, mean age 57.13 (+/- 10.7) years, height of 173.38
      (+/- 9) cm, weight 90.21 (+/- 16.9) and BMI of 30.07 (+/- 2.87) kg/m2. RESULTS:
      Postural balance improved after surgery, with a statistically significant
      decrease in the length of the sway path in the AP plane and a strong trend
      towards significance in the medio- lateral plane. The maximum deflection of the
      COP from the 0 in the Y direction was reduced. The average velocity of movement
      of the COP along the Y-axis was significantly reduced, and velocity along the X
      axis in mm/s was reduced with a strong trend towards significance. CONCLUSIONS:
      1. THA from a postero-lateral approach did not lead to a deterioration of
      postural stability in the early postoperative period. 2. Balance parameters,
      including path length and the average velocity of the COP in the antero-posterior
      plane, improved in a statistically significant manner. 3. The maximum extension
      of the COP in the frontal plane decreased with a strong trend towards
      significance.

PMID- 24662904
TI  - The gait pattern in post-menopausal women. Pilot study.
AB  - BACKGROUND: Aging brings about a number of degenerative changes in the body. The
      aging process in-creases its pace after the menopause. Women notice functional
      limitations in their daily lives, including mobility problems, as early as in
      their forties. Gait is one of the most reliable parameters reflecting the body's
      overall function and condition. The aim of this study was to determine the effect
      of menopause on gait patterns in healthy women. MATERIAL AND METHODS: The study
      involved a group of 48 healthy women (divided into Group A of pre-menopausal
      women and Group B of post-menopausal women). Gait parameters were acquired by a
      DynaPort MiniMod accelerometer. The pre- and post-menopausal women's gait data,
      including spatio-temporal parameters, gait cycle phases and the variability, were
      analysed. RESULTS: There were no significant differences between Group A and B in
      walking speed, step length, cadence, and gait phase duration. Significant
      differences were only noted in gait cycle phases with regard to the onset of
      single-support of the right limb, the 1st double-support of the right limb and
      the 2nd double-support of the left limb. Gait variability did not show any
      significant differences between the groups. CONCLUSIONS: 1. A prolonged stance
      phase during the gait cycle observed in the post-menopausal women in this study
      is a typical finding in aged people. 2. However, stride-to-stride variability of
      gait was not affected in the study.

PMID- 24662905
TI  - Is the postero-medial portal safe in posterior ankle arthroscopy?
AB  - BACKGROUND: Posterior ankle arthroscopy is considered to pose a risk of
      neurological and vascular complications. Some authors consider the postero-medial
      portal to be risky and recommend using only the postero-lateral portal. The aim
      of this study was to analyze the margin of error offered by posterior ankle
      arthroscopy portals. MATERIAL AND METHODS: Twenty MRI studies of the ankle joint
      were analyzed. The paths of the postero-medial and postero-lateral portals were
      drawn. Next, the path of the probe was diverged to aim at the neurovascular
      bundle and the angle of deviation was measured. We analyzed the distance between
      the probe located directly laterally to the flexor hallucis longus tendon and the
      neurovascular bundle. RESULTS: The mean angle of deviation leading to collision
      with neurovascular bundle structures was 53.3 degrees  (range 37-70 degrees ) and
      30.75 degrees  (range 22-41 degrees ) for the postero-medial and postero-lateral
      portals, respectively, p<0.05. The mean minimal distance between and the probe
      and the bundle was 12 mm (range 5-15 mm) and 13 mm (range 8-18 mm) for the
      postero-medial and postero-lateral portals, respectively, p>0.05. CONCLUSIONS: 1.
      The postero-medial arthroscopic portal is at least as safe as the postero-lateral
      one in posterior ankle arthroscopy. 2. Keeping instruments strictly laterally to
      the flexor hallucis longus tendon leaves at least 5 mm distance from the
      neurovascular bundle.

PMID- 24662906
TI  - Factors influencing bone regenerate healing in distraction osteogenesis.
AB  - BACKGROUND: The dynamics and effectiveness of new bone formation in the Ilizarov
      method varies according to different factors. Some of them may result in
      substantial prolongation of treatment time. The lengthening index (LI), defined
      as the number of months in a frame necessary to achieve 1 cm lengthening, is the
      main indicator of bone healing potential. The purpose of the study was to assess
      the effectiveness of distraction osteogenesis by analysing the lengthening index
      (LI) in relation to: age, limb length discrepancy, aetiology, bone segment
      involved, axial correction and lengthening achieved. We studied 251 patients
      between the ages of 3 to 50 years (mean 15.3) treated with the Ilizarov method
      because of lower limb inequality. A total of 319 lengthening procedures were
      analyzed (tibia--155, femur--164). MATERIAL AND METHODS: Total treatment time
      (time in a frame) and magnitude of lengthening were recorded in all patients to
      calculate LI (months per 1cm of lengthening). Patients were divided into several
      groups according to these factors. RESULTS: Mean LI in the entire sample was 1.6
      months/cm (from 0.7 to 5.9). The lowest LI (1.4) was recorded in the youngest
      patients (from 3 to 9 years) and increased with age, amounting to 1.6 in the 10
      17 years' age group, 1.7 in the 18-21 years' age group and 2.4 in the 22-50
      years' age group. The mean LI for femoral lengthening was lower (1.5) than for
      the tibias (1.8). In a group of 63 cases of lengthening up to 4 cm, LI was 2.3;
      in another group (from 4 to 7 cm - 189 procedures) LI was lower (1.6), and in the
      last group (more than 7 cm) it was 1.2. There was no significant difference in
      mean LI between the groups with and without axial correction. However,
      differences between aetiology groups were statistically significant, with a mean
      LI of 1.2 in achondroplasia patients, 1.4 in post-septic patients and patients
      with and Ollier disease, 1.6 in patients with congenital deformities, 1.8 in post
      traumatic patients and 2.0 in neurogenic and clubfoot patients. CONCLUSION:
      According to the lengthening index analysis, the effectiveness of distraction
      osteogenesis is related to age, aetiology, bone segment involved and the
      magnitude of lengthening, while it is not related to axial correction.

PMID- 24662907
TI  - Orthopedic procedures in patients with congenital coagulation disorders: single
      center experience.
AB  - BACKGROUND: Spontaneous intraarticular bleeds in congenital coagulation disorders
      result in early and extensive damage to the joints and periarticular structures.
      Total arthroplasty is the only effective method of treating these defects.
      Interim surgical procedures (arthroscopy, osteotomy, etc.) exist that can
      postpone arthroplasty, especially considering the fact that the condition affects
      young people. The aim of this paper is to discuss the range of trauma care and
      orthopedic procedures performed in patients with congenital coagulation
      disorders. Also presented are early results of joint arthroplasty in these
      patients. MATERIAL AND METHODS: A total of 168 trauma care and orthopedic
      procedures were performed in patients with congenital coagulation disorders at
      the Clinical Department of Orthopedics and Traumatology of the Central Clinical
      Hospital of the Ministry of Interior in Warsaw in the years 2010-2013. Among them
      were total arthroplasties (79 arthroplasties of the knee, 30 of the hip, 3 of the
      ankle and 1 of the elbow), arthroscopies, filling bone cysts with grafts and
      trauma procedures. The HHS, KSS, AOFAS and MEPS scales were used to evaluate the
      respective clinical results of hip, knee, ankle and elbow arthroplasty
      procedures. A VAS was used to evaluate pain intensity. In knee arthroplasty
      patients, quality of life parameters were evaluated with the WOMAC index.
      RESULTS: In patients post hip arthroplasty, HHS scores increased by 50.22 points
      and VAS scores increased by 6.34 points. An increase of 116.41 points in KSS
      scores and 6.67 points in VAS scores was recorded in patients after knee
      arthroplasty. Also, WOMAC scores improved by 53.8 points after surgery.
      Evaluation of early results of ankle arthroplasty in the AOFAS scale showed a
      mean improvement of 35.5 points and a 5-point improvement in VAS scores. MEPS
      scores, used for evaluation of elbow arthroplasty results, improved from 15 to 70
      points, with an improvement from 6 to 2 points in VAS scores. CONCLUSIONS: 1.
      Orthopedic procedures in patients with congenital coagulation disorders require
      thorough preparation of the patient and close cooperation between the orthopedic
      and hematological teams. 2. Early clinical outcomes are promising. 3. Decreased
      pain intensity, increased joint range of motion and improved quality of life post
      surgery are observed.

PMID- 24662908
TI  - Fracture risk prediction in outpatients from Krakow Region using FRAX tool versus
      fracture risk in 11-year follow-up.
AB  - INTRODUCTION: FRAX is a an algorithm accepted by WHO for evaluating fragility
      fracture risk of women aged 40 years or more. The aim of this study was to use
      the FRAX tool to verify the risk of fractures in a population of women from the
      Cracow region in an 11-year follow-up. MATERIALS AND METHODS: The study was a
      retrospective cohort survey evaluating the incidence of fragility fractures over
      11 years of follow-up. 5,092 women aged 50 years and more were randomly chosen
      from a group of 100,000 female patients of the Cracow Medical Centre who came to
      the Centre for densitometric examination between 1997 and 2001. Finally, 1024
      patients were randomized into the study. After an average of 11 years a follow-up
      telephone survey was conducted among a randomly selected group of patients using
      a questionnaire corresponding to the one applied in the first survey. 10-year
      fracture risk was calculated for each patient using FRAX based on the BMI (Body
      Mass Index) and for 886 women using FRAX based on BMD (Bone Mineral Density) at
      the femoral neck. The Polish version of FRAX was validated by comparing the
      predicted risk with the actual incidence of fractures during the 11-year follow
      up. RESULTS: The 10-year probability of a major osteoporotic fracture calculated
      using FRAX based on BMI for the entire group was 5.3% (median, 1st/3rd quartile:
      3.5-8.5%) and the probability of a proximal femur (hip) fracture was 1.3%
      (median, 1st-3rd quartile: 0.7% -2.4%). In 886 women whose BMD T-score at the
      femoral neck was available, the mean probability of a major osteoporotic fracture
      was 4.9% (3.3-7.9%) and of a hip fracture 0.9% (0.3-2.3%). The actual absolute
      fracture risk calculated on the basis of the number of patients who had
      experienced a fracture during the follow-up was surprisingly much higher than the
      predicted figure. The risk of a major fracture in the study group was 17.7% and
      of a proximal femur fracture, 3%. CONCLUSION: In our opinion, FRAX is a very good
      screening tool, but not a precise diagnostic tool.

PMID- 24662909
TI  - Role of the physiotherapist in the orthopaedic trauma department in the context
      of National Health Fund funding of medical procedures.
AB  - BACKGROUND: The present paper aims to demonstrate that physiotherapy in
      orthopaedic and trauma departments is part and parcel of a comprehensive
      treatment plan. MATERIAL AND METHODS: Hospital records of 66 patients treated in
      three orthopaedic trauma departments in 2011 were analysed. Basing on the
      requirements of the National Health Fund (Narodowy Fundusz Zdrowia--NFZ), reports
      were generated on the number of physiotherapy procedures provided. RESULTS: The
      mean age of the patients was 70.26 (SD=12.08) years. Sixty-two of them (93.94%)
      had undergone hip replacement and the remaining 4 (6.06%) had undergone knee
      replacement procedures. The patients spent a mean of 13 days in hospital
      (SD=3.66, range 9-30 days). The following physiotherapy procedures were applied:
      mobilisation in 48 subjects (72.73%), seating in 47 (71.21%), gait training in 48
      (72.73%), exercises of the affected leg in 46 (69.70%), upper limb exercises in
      38 (57.58%) and breathing exercises in 28 (42.42%). According to the NFZ
      regulations, the maximum number of patients per one physiotherapist in an
      orthopaedic department is 10, which requirement was met in only one of the three
      hospitals involved. CONCLUSIONS: 1. Arthroplasty procedures along with long bone
      fracture fixation are the most common causes of hospitalisation in orthopaedic
      trauma departments. 2. The departments involved in this study do not provide pre
      operative rehabilitation. Physiotherapy begins at 3 days post surgery. 3. Most of
      the departments involved do not comply with the NFZ's requirement regarding the
      therapist-to-patient ratio.

PMID- 24662910
TI  - Knowledge of participants of the 5th Polish Foot and Ankle Society (PFAS)
      Congress about the diagnosis and treatment of plano-valgus feet secondary to
      posterior tibial tendon dysfunction (PTTD).
AB  - BACKGROUND: Posterior tibial tendon dysfunction (PTTD) ranks among the most
      common causes of adult acquired flatfoot deformity. The deformity develops
      gradually through characteristic stages and its early manifestations are often
      ignored or mis-diagnosed. The aim of the study was to gain an insight into what
      the participants of the 5th Polish Foot and Ankle Society Congress knew about the
      diagnosis and treatment of flatfoot. MATERIAL AND METHODS: An anonymous survey
      described the clinical presentation of a hypothetical patient with fixed stage
      III (according to the Johnson and Strom classification) acquired flatfoot
      deformity in PTTD. A total of 65 questionnaires were distributed and 51 (78%)
      were completed and returned. The respondents included 40 orthopaedics consultants
      and 11 orthopaedics and traumatology resident doctors. The mean time of work
      experience of the specialists was 17.5 years and that of resident doctors, 3.5
      years. RESULTS: The deformity was properly diagnosed by 36 respondents (71%),
      including 29 specialists (73%) and 7 resident doctors (63%). Proper operative
      treatment was selected by 28 respondents (52%): 24 specialists (60%) and 4
      residents (36%). Overall, appropriate comprehensive diagnostic work-up and
      treatment was planned only by 19 respondents (35%), including 17 specialists
      (32%) and 2 residents (4%). Appropriate diagnostic work-up and treatment of
      acquired flatfoot deformity in PTTD was planned by less than half of the
      respondents and their work experience did not have any relation with the
      management they suggested. CONCLUSIONS: 1. There is a significant lack of
      knowledge about PTTD among residents. 2. The majority of PFAS members surveyed
      selected the correct method of diagnostic work-up and treatment, but the
      differences with respect to non-PFAS respondents were not statistically
      significant.

PMID- 24662911
TI  - Unusual operative treatment and outcome of femoral shaft fracture in a non
      ambulatory cerebral palsy patient.
AB  - Cerebral palsy patients are prone to spontaneous fractures due to poor bone
      quality. The treatment options of femoral fractures include conservative and
      operative management which is tailored according to the patient's needs, co
      morbidities and the presence of skilled surgeon. We present a 20 year old non
      ambulatory CP patient who had a fractured femoral shaft which was treated by
      surgical excision of the fracture which is a surgical modality that according to
      our knowledge hasn't been addressed before in literature. 

PMID- 24662912
TI  - Severe destructive arthritis of the carpometacarpal joint: a diagnosis of
      exclusion case report.
AB  - We present a case of severe destruction of the thumb carpometacarpal joint (CMCJ)
      and surrounding structures on a background of osteoarthritis and Seronegative
      Rheumatoid arthritis. Imaging studies suggested a soft tissue lesion consistent
      with Pigmented Villonodular Synovitis (PVNS), Synovial Osteochondromatosis or
      Giant Cell Tumour (GCT). Due to the possibility of malignant transformation and
      deteriorating symptoms the mass was excised. Histological analysis of the lesion
      revealed severe degenerative disease with no evidence of malignancy or infection.
      This represents an atypical presentation of thumb carpometacarpal joint
      arthritis, which should be diagnosed once more sinister pathology has been
      excluded. 

PMID- 24662913
TI  - The treatment of intertrochanteric fractures of the femur with endovis nail.

PMID- 24662914
TI  - A touch-screen based paired-associates learning (PAL) task for the rat may
      provide a translatable pharmacological model of human cognitive impairment.
AB  - The use of touch-screen equipped operant boxes is an increasingly popular
      approach for modeling human cognition in the rodent. However little data is
      currently available describing the effects of pharmacological manipulations on
      touch-screen based tasks. Owing to the relationship between performance on visual
      spatial paired associates learning (PAL) with schizophrenia and Alzheimer's
      disease one task of specific interest is the touch-screen PAL task developed for
      rodents (J. Talpos et al., 2009). The goal of this study was to profile a range
      of the commonly used pharmacological models of schizophrenia and Alzheimer's
      disease to investigate the sensitivity of PAL to these models of disease. Male
      Lister hooded rats were trained on PAL until stable performance was obtained. The
      effects of PCP, ketamine, amphetamine, LSD, scopolamine, and biperiden (recently
      proposed as an alternative to scopolamine) were then tested on animals performing
      the PAL task. While all compounds influenced responding during PAL, only PCP and
      amphetamine impaired performance with minimal changes in secondary measures
      (response latencies, trials completed). Surprisingly ketamine did not cause a
      change in percent correct despite being an NMDA antagonist, indicating that not
      all NMDA antagonists are equal in the touch-screen platform. This finding is in
      agreement with existing literature showing differential effects of NMDA
      antagonists on a wide variety of behavioral assays include tasks of attention,
      memory, and cognitive flexibility (Gilmour et al., 2009; Dix et al., 2010; Smith
      et al., 2011). Moreover biperiden showed no benefit when compared to scopolamine,
      highlighting the current lack of an effective pharmacological model of
      cholinergic dysfunction in the touch-screen platform. These data demonstrate that
      performance on PAL can be disrupted by common pharmacological disease models,
      suggesting that PAL may have the sensitivity to serve as a translational test for
      the study of cognition in humans. 

PMID- 24662915
TI  - Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic
      plasticity deficits in a rat model of schizophrenia.
AB  - Cognitive deficits are the core symptoms of schizophrenia and major contributors
      to disability in schizophrenic patients, but effective treatments are still
      lacking. Previous studies have demonstrated that impaired BDNF/TrkB signaling is
      associated with the cognitive impairments of schizophrenia. 7,8-Dihydroxyflavone
      (7,8-DHF) has recently been identified as a specific TrkB agonist that crosses
      the blood-brain barrier after oral or intraperitoneal administration. The present
      study aimed to assess the effect of 7,8-DHF on the cognitive and synaptic
      impairments of schizophrenia. A brief disruption of NMDA receptors with MK-801
      during early development serves as an animal model for cognitive deficits of
      schizophrenia. We found that MK-801-treated rats showed significant deficits in
      working learning ability and hippocampal synaptic plasticity, as well as
      reduction of BDNF, TrkB, and phosphorylated TrkB in the hippocampus. After
      intraperitoneal administration with 7,8-DHF (5 mg/kg) once daily for a
      consecutive 14days, we found that chronic 7,8-DHF treatment significantly
      enhanced the activation of phosphorylated TrkB at the Y515 and Y816 sites,
      increased the phosphorylation levels of TrkB downstream signal cascades including
      ERK1/2, CaMKII, CREB and GluR1, and promoted hippocampal synaptic plasticity,
      which in turn rescued performance in spatial working learning. Our results thus
      demonstrate that activation of TrkB signaling can reverse the cognitive deficits
      of schizophrenia and strongly suggest a potential usefulness for 7,8-DHF or a
      TrkB agonist in treating schizophrenia-related cognitive impairments.

PMID- 24662917
TI  - The "bacterial heterodisulfide" DsrC is a key protein in dissimilatory sulfur
      metabolism.
AB  - DsrC is a small protein present in organisms that dissimilate sulfur compounds,
      working as a physiological partner of the DsrAB sulfite reductase. DsrC contains
      two redox active cysteines in a flexible carboxy-terminal arm that are involved
      in the process of sulfite reduction or sulfur(1) compound oxidation in sulfur
      reducing(2) or sulfur-oxidizing(3) organisms, respectively. In both processes, a
      disulfide formed between the two cysteines is believed to serve as the substrate
      of several proteins present in these organisms that are related to
      heterodisulfide reductases of methanogens. Here, we review the information on
      DsrC and its possible physiological partners, and discuss the idea that this
      protein may serve as a redox hub linking oxidation of several substrates to
      dissimilative sulfur metabolism. In addition, we analyze the distribution of
      proteins of the DsrC superfamily, including TusE that only requires the last Cys
      of the C-terminus for its role in the biosynthesis of 2-thiouridine, and a new
      protein that we name RspA (for regulatory sulfur-related protein) that is
      possibly involved in the regulation of gene expression and does not need the
      conserved Cys for its function. This article is part of a Special Issue entitled:
      18th European Bioenergetic Conference. 

PMID- 24662916
TI  - The Mu opioid receptor promotes opioid and growth factor-induced proliferation,
      migration and Epithelial Mesenchymal Transition (EMT) in human lung cancer.
AB  - Recent epidemiologic studies implying differences in cancer recurrence based on
      anesthetic regimens raise the possibility that the mu opioid receptor (MOR) can
      influence cancer progression. Based on our previous observations that
      overexpression of MOR in human non-small cell lung cancer (NSCLC) cells increased
      tumor growth and metastasis, this study examined whether MOR regulates growth
      factor receptor signaling and epithelial mesenchymal transition (EMT) in human
      NSCLC cells. We utilized specific siRNA, shRNA, chemical inhibitors and
      overexpression vectors in human H358 NSCLC cells that were either untreated or
      treated with various concentrations of DAMGO, morphine, fentanyl, EGF or IGF.
      Cell function assays, immunoblot and immunoprecipitation assays were then
      performed. Our results indicate MOR regulates opioid and growth factor-induced
      EGF receptor signaling (Src, Gab-1, PI3K, Akt and STAT3 activation) which is
      crucial for consequent human NSCLC cell proliferation and migration. In addition,
      human NSCLC cells treated with opioids, growth factors or MOR overexpression
      exhibited an increase in snail, slug and vimentin and decrease ZO-1 and claudin-1
      protein levels, results consistent with an EMT phenotype. Further, these effects
      were reversed with silencing (shRNA) or chemical inhibition of MOR, Src, Gab-1,
      PI3K, Akt and STAT3 (p<0.05). Our data suggest a possible direct effect of MOR on
      opioid and growth factor-signaling and consequent proliferation, migration and
      EMT transition during lung cancer progression. Such an effect provides a
      plausible explanation for the epidemiologic findings. 

PMID- 24662919
TI  - Emergence, involution, and progression to carcinoma of mutant clones in normal
      endometrial tissues.
AB  - Sporadic somatic inactivation of genes such as PTEN within histologically normal
      endometrium (latent precancers) is an early step in endometrial carcinogenesis.
      We have used clone-specific mutations of PTEN to determine the fate of latent
      precancers over time in women who do (high risk) and do not (low risk) develop
      endometrial neoplasia. PTEN immunohistochemistry was performed on 45 occurrences
      of endometrial neoplasia and their paired antecedent benign biopsies, along with
      age matched sample pairs from 167 patients who did not develop a neoplasm. When
      PTEN-deficient cells were present at both time points, DNA sequencing was
      performed to determine whether they were single or multiple independent events.
      Loss of PTEN protein in isolated glands was common in the initial normal biopsies
      of high- and low-risk groups (42% and 27%, respectively, P = 0.066). Protein
      deficient glands have a tendency to disappear over time in low-risk women (P =
      0.047) and, even when "persistent," are infrequently (19%, 3/16) confirmed to be
      the same clone. Similarly, only a small proportion (6.7%, 1/15) of latent
      precancers seen in high-risk women are the direct progenitors of subsequent
      neoplasia. There is a high rate of latent precancer turnover in both low- and
      high-risk patients, with rare long-term persistence of unique clones, which may
      or may not progress to a histologic lesion. The temporal dynamics of clonal
      emergence, persistence, and involution are sufficiently complex that in the
      individual patient, the presence of a latent precancer has an unknown
      contribution to long-term cancer risk.

PMID- 24662918
TI  - Identification and characterization of small molecules that inhibit nonsense
      mediated RNA decay and suppress nonsense p53 mutations.
AB  - Many of the gene mutations found in genetic disorders, including cancer, result
      in premature termination codons (PTC) and the rapid degradation of their mRNAs by
      nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a
      pocket in the SMG7 protein, a key component of the NMD mechanism, to identify
      compounds that disrupt the SMG7-UPF1 complex and inhibit NMD. Several of these
      compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with
      minimal toxicity in cell-based assays. As expected, pharmacologic NMD inhibition
      disrupted SMG7-UPF1 interactions. When used in cells with PTC-mutated p53,
      pharmacologic NMD inhibition combined with a PTC "read-through" drug led to
      restoration of full-length p53 protein, upregulation of p53 downstream
      transcripts, and cell death. These studies serve as proof-of-concept that
      pharmacologic NMD inhibitors can restore mRNA integrity in the presence of PTC
      and can be used as part of a strategy to restore full-length protein in a variety
      of genetic diseases.

PMID- 24662922
TI  - Synthesis of luminescent europium defects in diamond.
AB  - Lanthanides are vital components in lighting, imaging technologies and future
      quantum memory applications owing to their narrow optical transitions and long
      spin coherence times. Recently, diamond has become a pre-eminent platform for the
      realisation of many experiments in quantum information science. Here we
      demonstrate a promising approach to incorporate Eu ions into diamond, providing a
      means to harness the exceptional characteristics of both lanthanides and diamond
      in a single material. Polyelectrolytes are used to electrostatically assemble
      Eu(III) chelate molecules on diamond and subsequently chemical vapour deposition
      is employed for the diamond growth. Fluorescence measurements show that the Eu
      atoms retain the characteristic optical signature of Eu(III) upon incorporation
      into the diamond lattice. Computational modelling supports the experimental
      findings, corroborating that Eu(III) in diamond is a stable configuration. The
      formed defects demonstrate the outstanding chemical control over the
      incorporation of impurities into diamond enabled by the electrostatic assembly
      together with chemical vapour deposition growth. 

PMID- 24662920
TI  - ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1
      deficiency.
AB  - The DNA damage response kinase ATR and its effector kinase CHEK1 are required for
      cancer cells to survive oncogene-induced replication stress. ATR inhibitors
      exhibit synthetic lethal interactions, with deficiencies in the DNA damage
      response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase
      cyclin E. Here, we report a systematic screen to identify synthetic lethal
      interactions with ATR pathway-targeted drugs, rationalized by their predicted
      therapeutic utility in the oncology clinic. We found that reduced function in the
      ATR pathway itself provided the strongest synthetic lethal interaction. In
      addition, we found that loss of the structure-specific endonuclease ERCC1-XPF
      (ERCC4) is synthetic lethal with ATR pathway inhibitors. ERCC1-deficient cells
      exhibited elevated levels of DNA damage, which was increased further by ATR
      inhibition. When treated with ATR or CHEK1 inhibitors, ERCC1-deficient cells were
      arrested in S-phase and failed to complete cell-cycle transit even after drug
      removal. Notably, triple-negative breast cancer cells and non-small cell lung
      cancer cells depleted of ERCC1 exhibited increased sensitivity to ATR pathway
      targeted drugs. Overall, we concluded that ATR pathway-targeted drugs may offer
      particular utility in cancers with reduced ATR pathway function or reduced levels
      of ERCC4 activity.

PMID- 24662921
TI  - Mislocalization of the cell polarity protein scribble promotes mammary
      tumorigenesis and is associated with basal breast cancer.
AB  - Scribble (SCRIB) localizes to cell-cell junctions and regulates establishment of
      epithelial cell polarity. Loss of expression of SCRIB functions as a tumor
      suppressor in Drosophila and mammals; conversely, overexpression of SCRIB
      promotes epithelial differentiation in mammals. Here, we report that SCRIB is
      frequently amplified, mRNA overexpressed, and protein is mislocalized from cell
      cell junctions in human breast cancers. High levels of SCRIB mRNA are associated
      with poor clinical prognosis, identifying an unexpected role for SCRIB in breast
      cancer. We find that transgenic mice expressing a SCRIB mutant [Pro 305 to Leu
      (P305L)] that fails to localize to cell-cell junctions, under the control of the
      mouse mammary tumor virus long terminal repeat promoter, develop multifocal
      hyperplasia that progresses to highly pleomorphic and poorly differentiated
      tumors with basal characteristics. SCRIB interacts with phosphatase and tensin
      homolog (PTEN) and the expression of P305L, but not wild-type SCRIB, promotes an
      increase in PTEN levels in the cytosol. Overexpression of P305L, but not wild
      type SCRIB, activates the Akt/mTOR/S6K signaling pathway. Human breast tumors
      overexpressing SCRIB have high levels of S6K but do not harbor mutations in PTEN
      or PIK3CA, identifying SCRIB amplification as a mechanism of activating PI3K
      signaling in tumors without mutations in PIK3CA or PTEN. Thus, we demonstrate
      that high levels of mislocalized SCRIB functions as a neomorph to promote mammary
      tumorigenesis by affecting subcellular localization of PTEN and activating an
      Akt/mTOR/S6kinase signaling pathway.

PMID- 24662923
TI  - Association of a vascular endothelial growth factor polymorphism with the
      development of bronchopulmonary dysplasia in Japanese premature newborns.
AB  - Our objective was to correlate vascular endothelial growth factor (VEGF) genetic
      polymorphisms with the risk of bronchopulmonary dysplasia (BPD) development in
      premature newborns. Fifty-five newborns with BPD (BPD: median gestational age
      [GA]: 27 weeks, birthweight [BW]: 786 g) and 42 newborns without BPD (non-BPD:
      median GA: 29 weeks, BW: 1,165 g), who were born at <32 weeks gestational age and
      were admitted to Kobe University Hospital, were included. BPD was defined as
      oxygen dependency at 36 weeks postmenstrual age. Genomic DNA was extracted from
      the umbilical cord, cord blood, or buccal mucosa. Six VEGF genotypes (-1498T > C,
      -1154G > A, -634C > G, -7C > T, 936C > T, and 1612G > A) were determined by DNA
      sequencing. Clinical characteristics, and allele and genotype frequencies of VEGF
      in the BPD and non-BPD groups were analyzed. G allele frequencies in -634C > G of
      the BPD group were significantly higher than in the non-BPD group (66.4% vs. 50%,
      P = 0.02). -634C > G genotype distributions differed significantly between the
      BPD and non-BPD groups (BPD: CC 7%/CG 53%/GG 40%; non-BPD: CC 24%/CG 52%/GG 24%;
      P = 0.04). Multivariate logistic regression showed that duration of ventilation,
      VEGF-634G > C G alleles, and male gender were independent risk factors for BPD.
      In conclusion, polymorphism VEGF -634C > G may influence the risk of BPD.

PMID- 24662924
TI  - Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in
      8p11-p12-amplified breast carcinomas.
AB  - Genetic and epigenetic (DNA methylation, histone modifications, microRNA
      expression) crosstalk promotes inactivation of tumor suppressor genes or
      activation of oncogenes by gene loss/hypermethylation or
      duplications/hypomethylation, respectively. The 8p11-p12 chromosomal region is a
      hotspot for genomic aberrations (chromosomal rearrangements, amplifications and
      deletions) in several cancer forms, including breast carcinoma where
      amplification has been associated with increased proliferation rates and reduced
      patient survival. Here, an integrative genomics screen (DNA copy number,
      transcriptional and DNA methylation profiling) performed in 229 primary invasive
      breast carcinomas identified substantial coamplification of the 8p11-p12 genomic
      region and the MYC oncogene (8q24.21), as well as aberrant methylation and
      transcriptional patterns for several genes spanning the 8q12.1-q24.22 genomic
      region (ENPP2, FABP5, IMPAD1, NDRG1, PLEKHF2, RRM2B, SQLE, TAF2, TATDN1, TRPS1,
      VPS13B). Taken together, our findings suggest that MYC activity and aberrant DNA
      methylation may also have a pivotal role in the aggressive tumor phenotype
      frequently observed in breast carcinomas harboring 8p11-p12 regional
      amplification. 

PMID- 24662925
TI  - Intraperitoneal administration of docosahexaenoic acid for 14days increases serum
      unesterified DHA and seizure latency in the maximal pentylenetetrazol model.
AB  - Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA)
      which has been shown to raise seizure thresholds following acute administration
      in rats. The aims of the present experiment were the following: 1) to test
      whether subchronic DHA administration raises seizure threshold in the maximal
      pentylenetetrazol (PTZ) model 24h following the last injection and 2) to
      determine whether the increase in seizure threshold is correlated with an
      increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.)
      injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle
      (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested
      in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested)
      subset of animals, blood was collected, and brains were excised following high
      energy, head-focused microwave fixation. Lipid analysis was performed on serum
      and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were
      combined since they did not differ significantly from each other. In the maximal
      PTZ model, DHA significantly increased seizure latency by approximately 3-fold as
      compared to vehicle-injected animals. This increase in seizure latency was
      associated with an increase in serum unesterified DHA. Total brain DHA and brain
      unesterified DHA concentrations, however, did not differ significantly in the
      treatment and control groups. An increase in serum unesterified DHA concentration
      reflecting increased flux of DHA to the brain appears to explain changes in
      seizure threshold, independent of changes in brain DHA concentrations. 

PMID- 24662926
TI  - Antibodies to NMDA receptor, blood-brain barrier disruption and schizophrenia: a
      theory with unproven links.

PMID- 24662928
TI  - Estrogen receptor beta and Liver X receptor beta: biology and therapeutic
      potential in CNS diseases.
AB  - In the last decade of the twentieth century, two nuclear receptors were
      discovered in our laboratory and, very surprisingly, were found to have key roles
      in the central nervous system. These receptors have provided some novel insights
      into the etiology and progression of neurodegenerative diseases and anxiety
      disorders. The two receptors are estrogen receptor beta (ERbeta) and liver X
      receptor beta (LXRbeta). Both ERbeta and LXRbeta have potent anti-inflammatory
      activities and, in addition, LXRbeta is involved in the genesis of dopaminergic
      neurons during development and protection of these neurons against
      neurodegeneration in adult life. ERbeta is involved in migration of cortical
      neurons and calretinin-positive GABAergic interneurons during development and
      maintenance of serotonergic neurons in adults. Both receptors are present in
      magnocellular neurons of the hypothalamic preoptic area including those
      expressing vasopressin and oxytocin. As both ERbeta and LXRbeta are ligand
      activated transcription factors, their ligands hold great potential in the
      treatment of diseases of the CNS. 

PMID- 24662927
TI  - Astrocytic abnormalities and global DNA methylation patterns in depression and
      suicide.
AB  - Astrocytes are glial cells specific to the central nervous system and involved in
      numerous brain functions, including regulation of synaptic transmission and of
      immune reactions. There is mounting evidence suggesting astrocytic dysfunction in
      psychopathologies such as major depression, however, little is known about the
      underlying etiological mechanisms. Here we report a two-stage study investigating
      genome-wide DNA methylation associated with astrocytic markers in depressive
      psychopathology. We first characterized prefrontal cortex samples from 121
      individuals (76 who died during a depressive episode and 45 healthy controls) for
      the astrocytic markers GFAP, ALDH1L1, SOX9, GLUL, SCL1A3, GJA1 and GJB6. A subset
      of 22 cases with consistently downregulated astrocytic markers was then compared
      with 17 matched controls using methylation binding domain-2 (MBD2) sequencing
      followed by validation with high-resolution melting and bisulfite Sanger
      sequencing. With these data, we generated a genome-wide methylation map unique to
      altered astrocyte-associated depressive psychopathology. The map revealed
      differentially methylated regions (DMRs) between cases and controls, the majority
      of which displayed reduced methylation levels in cases. Among intragenic DMRs,
      those found in GRIK2 (glutamate receptor, ionotropic kainate 2) and BEGAIN (brain
      enriched guanylate kinase-associated protein) were most significant and also
      showed significant correlations with gene expression. Cell-sorted fractions were
      investigated and demonstrated an important non-neuronal contribution of
      methylation status in BEGAIN. Functional cell assays revealed promoter and
      enhancer-like properties in this region that were markedly decreased by
      methylation. Furthermore, a large number of our DMRs overlapped known
      Encyclopedia of DNA elements (ENCODE)-identified regulatory elements. Taken
      together, our data indicate significant differences in the methylation patterns
      specific to astrocytic dysfunction associated with depressive psychopathology,
      providing a potential framework for better understanding this disease phenotype. 

PMID- 24662929
TI  - Neuropsychological mechanism underlying antidepressant effect: a systematic meta
      analysis.
AB  - Antidepressants are widely used in clinical practice for the treatment of
      depression and other mood disorders. Numerous neuroimaging studies have recently
      examined how antidepressants influence emotional processes. However, both
      clinical trials and neuroimaging studies have reported inconsistent responses to
      antidepressants. Moreover, the neuropsychological mechanisms by which
      antidepressants act to improve depressive features remain underspecified. This
      systematic meta-analysis summarizes pharmacological neuroimaging studies (before
      February 2013) and the antidepressant effects on human brain activity underlying
      emotional processes. Sixty fMRI studies (involving 1569 subjects) applying
      antidepressants vs control were included in the current quantitative Activation
      Likelihood Estimation (ALE) meta-analysis. Pooling of results by ALE meta
      analyses was stratified for population (mood disorder patients/healthy
      volunteers), emotional valence (positive/negative emotions) and treatment effects
      (increased/decreased brain activity). For both patients and healthy volunteers,
      the medial prefrontal and core limbic parts of the emotional network (for
      example, anterior cingulate, amygdala and thalamus) were increased in response to
      positive emotions but decreased to negative emotions by repeated antidepressant
      administration. Moreover, selective antidepressant effects were uncovered in
      patients and healthy volunteers, respectively. Antidepressants increased activity
      in the dorsolateral prefrontal (dlPFC), a key region mediating emotion
      regulation, during both negative and positive emotions in patients. Repeated
      antidepressant administration decreased brain responses to positive emotions in
      the nucleus accumbens, putamen, medial prefrontal and midbrain in healthy
      volunteers. Antidepressants act to normalize abnormal neural responses in
      depressed patients by increasing brain activity to positive stimuli and
      decreasing activity to negative stimuli in the emotional network, and increasing
      engagement of the regulatory mechanism in dlPFC. 

PMID- 24662930
TI  - Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR
      image analysis--potential role as biomarker of response to ranibizumab treatment.
AB  - PURPOSE: To evaluate the influence of a ranibizumab treatment on microaneurysm
      (MA) turnover in diabetic retinopathy. METHODS: Sixty-nine eyes were included in
      this retrospective study. We compared a group of 33 eyes with ranibizumab
      treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic
      retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy
      (Optomap) images were obtained at a mean 4.76 +/- 1.69 days prior to the first
      ranibizumab injection (baseline) and again 35.94 +/- 2.44 days after the third
      consecutive injection in a 4-week interval. In untreated controls, images were
      obtained at baseline and 97.81 +/- 3.16 days thereafter. Images were analyzed
      using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the
      turnover of MAs was documented and analyzed. Thereafter, MA turnover was
      correlated with central retinal thickness (CRT) as assessed by OCT. RESULTS: At
      baseline, patients in the treatment group had 5.64 +/- 0.75 MAs. One month after
      3 ranibizumab injections, measured MAs decreased to 4.03 +/- 0.66. In the
      untreated control group, the initial number of 3.36 +/- 0.6 MAs remained almost
      unchanged over 3-4 months (2.89 +/- 0.57 MAs). Dynamic analysis showed that after
      ranibizumab treatment 3.06 +/- 0.5 new MAs appeared, while 5.09 +/- 0.79
      disappeared. In the control group, 2.11 +/- 0.4 new MAs appeared and 2.61 +/-
      0.48 disappeared. MA turnover was significantly higher with ranibizumab compared
      to the control group (8.15 +/- 1.14 vs. 4.72 +/- 0.81, p < 0.001). Consistently,
      CRT decreased from 444 to 330 um in the ranibizumab group, while there was no
      change in the control group (291 vs. 288 um). CONCLUSION: The treatment of
      macular edema using ranibizumab does not only reduce macular thickness, but also
      has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR
      analysis showed that more pre-existent MAs disappeared than new MAs developed,
      and the absolute number of MAs also decreased.

PMID- 24662934
TI  - Author's reply: To PMID 19535999.

PMID- 24662931
TI  - Development of broadly neutralizing antibodies from autologous neutralizing
      antibody responses in HIV infection.
AB  - PURPOSE OF REVIEW: Detailed genetic and structural characterization has revealed
      that broadly neutralizing antibodies (bnAbs) against HIV-1 have unusually high
      levels of somatic hypermutation, long CDRH3 domains, and the ability to target
      one of four sites of vulnerability on the HIV-1 envelope (Env) glycoproteins. A
      current priority is to understand how bnAbs are generated during natural
      infection, and translate this information into immunogens that can elicit bnAb
      following vaccination. RECENT FINDINGS: Strain-specific neutralizing antibodies
      can acquire broad neutralizing capacity when the transmitted/founder Env or a
      specific Env variant is recognized by an unmutated rearranged germline that has
      the capacity to develop bnAb-like features. This event could be relatively
      infrequent, as only certain germlines appear to possess inherent features needed
      for bnAb activity. Furthermore, the glycosylation pattern and diversity of
      circulating HIV-1 Envs, as well as the state of the B-cell compartment, may
      influence the activation and maturation of certain antibody lineages. SUMMARY:
      Collectively, studies over the last year have suggested that the development of
      HIV-1 Env immunogens that bind and activate bnAb-like germlines is feasible.
      However, more information about the features of Env variants and the host factors
      that lead to breadth during natural infection are needed to elicit bnAbs through
      immunization.

PMID- 24662935
TI  - Chemical composition, antioxidant, anti-inflammatory and anti-proliferative
      activities of essential oils of plants from Burkina Faso.
AB  - This research highlights the chemical composition, antioxidant, anti-inflammatory
      and anti-proliferative activities of essential oils from leaves of Ocimum
      basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum
      conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were
      analyzed by gas chromatography-mass spectrometry and gas chromatography-flame
      ionization detector. Major constituents were alpha-terpineol (59.78%) and beta
      caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor
      (12.730%), alpha-pinene (6.87%) and trans alpha-bergamotene (5.32%) for Ocimum
      americanum; beta-caryophyllene (21%), alpha-pinene (20.11%), sabinene (10.26%),
      beta-pinene (9.22%) and alpha-phellandrene (7.03%) for Hyptis spicigera; p-cymene
      (25.27%), beta-caryophyllene (12.70%), thymol (11.88), gamma-terpinene (9.17%)
      and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum
      conyzoides; eucalyptol (59.55%), alpha-pinene (9.17%) and limonene (8.76%) for
      Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene
      (8.40%), beta-bisabolene (7.83%) and beta-sesquiphellandrene (5.34%) for Zingiber
      officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl
      hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)
      methods. O. basilicum and L. multiflora exhibited the highest antioxidant
      activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were
      evaluated by measuring the inhibition of lipoxygenase activity and essential oil
      of Z. officinale was the most active. Anti-proliferative effect was assayed by
      the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763
      and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L.
      multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The
      SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L.
      multiflora EOs while essential oil of A. conyzoides showed the highest activity
      on SF-763 cells. Altogether these results justify the use of these plants in
      traditional medicine in Burkina Faso and open a new field of investigation in the
      characterization of the molecules involved in anti-proliferative processes. 

PMID- 24662936
TI  - Density functional theory calculations of continuum lowering in strongly coupled
      plasmas.
AB  - An accurate description of the ionization potential depression of ions in plasmas
      due to their interaction with the environment is a fundamental problem in plasma
      physics, playing a key role in determining the ionization balance, charge state
      distribution, opacity and plasma equation of state. Here we present a method to
      study the structure and position of the continuum of highly ionized dense plasmas
      using finite-temperature density functional theory in combination with excited
      state projector augmented-wave potentials. The method is applied to aluminium
      plasmas created by intense X-ray irradiation, and shows excellent agreement with
      recently obtained experimental results. We find that the continuum lowering for
      ions in dense plasmas at intermediate temperatures is larger than predicted by
      standard plasma models and explain this effect through the electronic structure
      of the valence states in these strong-coupling conditions. 

PMID- 24662939
TI  - The Role of STAT3 in Thyroid Cancer.
AB  - Thyroid cancer is the most common endocrine malignancy and its global incidence
      rates are rapidly increasing. Although the mortality of thyroid cancer is
      relatively low, its rate of recurrence or persistence is relatively high,
      contributing to incurability and morbidity of the disease. Thyroid cancer is
      mainly treated by surgery and radioiodine remnant ablation, which is effective
      only for non-metastasized primary tumors. Therefore, better understanding of the
      molecular targets available in this tumor is necessary. Similarly to many other
      tumor types, oncogenic molecular alterations in thyroid epithelium include
      aberrant signal transduction of the mitogen-activated protein kinase,
      phosphatidylinositol 3-kinase/AKT (also known as protein kinase B), NF-kB, and
      WNT/beta-catenin pathways. However, the role of the Janus kinase (JAK)/signal
      transducer and activator of transcription (STAT3) pathway, a well-known mediator
      of tumorigenesis in different tumor types, is relatively less understood in
      thyroid cancer. Intriguingly, recent studies have demonstrated that, in thyroid
      cancer, the JAK/STAT3 pathway may function in the context of tumor suppression
      rather than promoting tumorigenesis. In this review, we provide an update of
      STAT3 function in thyroid cancer and discuss some of the evidences that support
      this hypothesis. 

PMID- 24662938
TI  - Genetic Interactions of STAT3 and Anticancer Drug Development.
AB  - Signal transducer and activator of transcription 3 (STAT3) plays critical roles
      in tumorigenesis and malignant evolution and has been intensively studied as a
      therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated
      for their antitumor activity in vitro and in vivo in experimental tumor models
      and several approved therapeutic agents have been reported to function as STAT3
      inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to
      clinical evaluation for cancer treatment, presumably because of pharmacokinetic,
      efficacy, and safety issues. In fact, a major cause of failure of anticancer drug
      development is lack of efficacy. Genetic interactions among various cancer
      related pathways often provide redundant input from parallel and/or cooperative
      pathways that drives and maintains survival environments for cancer cells,
      leading to low efficacy of single-target agents. Exploiting genetic interactions
      of STAT3 with other cancer-related pathways may provide molecular insight into
      mechanisms of cancer resistance to pathway-targeted therapies and strategies for
      development of more effective anticancer agents and treatment regimens. This
      review focuses on functional regulation of STAT3 activity; possible interactions
      of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation
      pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3
      inhibitors. 

PMID- 24662940
TI  - Isolation of circulating tumor cells by dielectrophoresis.
AB  - Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic
      dielectric properties of suspended cells to be exploited for discrimination and
      separation. It has emerged as a promising method for isolating circulation tumor
      cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface
      markers. Furthermore, isolated CTCs are viable and can be maintained in culture,
      suggesting that DEP methods should be more generally applicable than antibody
      based approaches. The aim of this article is to review and synthesize for both
      oncologists and biomedical engineers interested in CTC isolation the pertinent
      characteristics of DEP and CTCs. The aim is to promote an understanding of the
      factors involved in realizing DEP-based instruments having both sufficient
      discrimination and throughput to allow routine analysis of CTCs in clinical
      practice. The article brings together: (a) the principles of DEP; (b) the
      biological basis for the dielectric differences between CTCs and blood cells; (c)
      why such differences are expected to be present for all types of tumors; and (d)
      instrumentation requirements to process 10 mL blood specimens in less than 1 h to
      enable routine clinical analysis. The force equilibrium method of
      dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher
      discrimination and throughput than earlier DEP trapping methods and to be
      applicable to clinical studies. 

PMID- 24662941
TI  - The coronary dilation effect of shen fu injection was mediated through NO.
AB  - OBJECTIVES: Shen Fu Injection (SF), which consisted of Red ginseng extraction
      injection (RG) and prepared aconite extraction injection (RA), is a traditional
      Chinese medicine mainly used for various cardiac diseases. This study is to
      analyse SF's effects on cardiac performance and coronary circulation. And the
      coronary dilating effect and mechanism of the above three injections were also
      explored. METHODS: Mature male guinea pigs were used as our animal model. We
      employed two types of perfusion methods (constant pressure and constant flow) in
      vitro, using Langendorff heart preparations to observe the cardiac function and
      coronary response to SF (1/200). The coronary dilation effects of the above three
      injections (1/800, 1/400 and 1/200) were recorded at basal coronary resting tone
      and when coronary vessels were pre-contracted with a thromboxane A2 analogue
      (U46619), in the presence or the absence of the inhibitor of nitric oxide
      synthesis (L-NAME, 10-4 M), the blocker of Ca2+-activated potassium channel(TEA,
      10-3 M), or the blocker of adenosine triphosphate (ATP)-sensitive potassium
      channel (glybenclamide) (10-5 M). RESULTS: When perfused with constant pressure,
      SF significantly increased coronary flow, left ventricular developed pressure
      (LVDP) and the rate-pressure product (RPP). When perfused with constant flow, SF
      produced a significant reduction in the coronary perfusion pressure (CPP), LVDP
      and RPP. The coronary vasodilatation response of the above three injections can
      be reduced by L-NAME but was unaffected by TEA or glybenclamide when coronary
      vessels were pre-contracted with U46619 but not at resting tone. SF, RG and RA
      can all up-regulate eNOS expression in the human umbilical vein cells (EA.hy926).
      CONCLUSION: We demonstrated that SF does not contribute to the inotropic change
      of myocardium whose improvement is due to alternation of coronary flow. The
      coronary dilation effect of SF was mediated through RG and RA, via promoting NO
      release.

PMID- 24662943
TI  - Childhood-onset primary generalized epilepsy--impacts on children's preferences
      for participation in out-of-school activities.
AB  - The purpose of this study was to compare preferences for participation in out-of
      school activities between children with childhood-onset primary generalized
      epilepsy and their healthy peers. Overall, participants were 56 children aged 6
      11 years. The study group included 26 children with childhood-onset primary
      generalized epilepsy. The controls were 30 healthy children. Parents of all
      participants completed a demographic and health status questionnaire. All
      children completed the Preference Assessment of Children (PAC) that profiles the
      out-of-school activities the child wishes to participate in. Scores are
      calculated for five activity types, namely, recreational, active physical,
      social, skill-based, and self-improvement and for two domains of formal and
      informal activities. Children with generalized epilepsy showed a similar
      preference for participation in out-of-school activities as did their healthy
      peers. The study group showed a lower preference for participation in social
      activities but showed a higher preference for participation in self-improvement
      activities. In both groups, younger children (aged 6-8 years) showed a lower
      preference for participation in most PAC scales. Older children (aged 9-11 years)
      showed a higher preference for participation in social activities. Difference
      between genders was close to being statistically significant in the skill-based
      activities (F(1,21)=3.84, p=.06), where girls showed a higher preference compared
      with boys. Intervention policies need to be undertaken in order to encourage
      children with epilepsy to participate in activities together with their healthy
      peers, aiming to enhance the well-being of children with primary generalized
      epilepsy.

PMID- 24662944
TI  - Hemichorea associated with nonketotic hyperglycemia: clinical and neuroimaging
      features in 12 patients.
AB  - BACKGROUND: Nonketotic hyperglycemia is a rare cause of hemichorea. Patients with
      hemichorea associated with nonketotic hyperglycemia (HCNH) always have a
      favorable prognosis when given prompt treatment. METHODS: We reviewed the medical
      records of 12 patients with HCNH in our hospital between January 2005 and January
      2013. The clinical data, laboratory findings, and imaging features of the
      patients were collected. RESULTS: All 12 patients were admitted to the hospital
      with a complaint of involuntary movements. Ten patients had a history of
      diabetes, while the other 2 patients had not been diagnosed. The mean level of
      blood glucose on admission was 330.7 +/- 107.8 mg/dl, and the ketones were
      negative. A cranial computed tomography scan showed hyperdensity in the striatum,
      which quickly resolved. Magnetic resonance imaging showed hyperintensity on T1
      weighted images without change over several months. Nearly all of the patients
      experienced relief from the hemichorea symptoms after correcting hyperglycemia
      with a combination of dopamine receptor inhibitors and the sedative lorazepam, if
      necessary. CONCLUSION: HCNH is a benign disorder, the pathogenesis of which
      remains unclear. Radiologic changes can provide guidance for early treatment and
      generally give an estimation of the degree of injury.

PMID- 24662945
TI  - Hydrogel microfluidics for the patterning of pluripotent stem cells.
AB  - Biomolecular signaling is of utmost importance in governing many biological
      processes such as the patterning of the developing embryo where biomolecules
      regulate key cell-fate decisions. In vivo, these factors are presented in a
      spatiotemporally tightly controlled fashion. Although state-of-the-art
      microfluidic technologies allow precise biomolecule delivery in time and space,
      long-term (stem) cell culture at the micro-scale is often far from ideal due to
      medium evaporation, limited space for cell growth or shear stress. To overcome
      these challenges, we here introduce a concept based on hydrogel microfluidics for
      decoupling conventional, macro-scale cell culture from precise biomolecule
      delivery through a gel layer. We demonstrate the spatiotemporally controlled
      neuronal commitment of mouse embryonic stem cells via delivery of retinoic acid
      gradients. This technique should be useful for testing the effect of dose and
      timing of biomolecules, singly or in combination, on stem cell fate. 

PMID- 24662946
TI  - Stabilized human TRIM5alpha protects human T cells from HIV-1 infection.
AB  - Rhesus (rh) but not human (hu) TRIM5alpha potently restricts human
      immunodeficiency virus (HIV)-1 infection. It is not clear why huTRIM5alpha fails
      to effectively block HIV infection, but it is thought to have a lower affinity
      for the viral core. Using primary human CD4 T cells, we investigated the ability
      of huTRIM5alpha, rhTRIM5alpha, and the huTRIM5alphaR323-332 B30.2/SPRY patch
      mutant to form cytoplasmic bodies, postulated as key components of the HIV-1
      restriction apparatus. Both rhTRIM5alpha and huTRIM5alphaR323-332 formed
      pronounced cytoplasmic bodies, whereas cytoplasmic bodies in T cells
      overexpressing huTRIM5alpha were present but more difficult to detect. As
      expression of all three TRIM5alpha orthologs was similar at the RNA level, we
      next investigated the role of protein stability in conferring TRIM5alpha-mediated
      HIV-1 restriction. Both steady-state and pulse-chase experiments revealed that
      the huTRIM5alpha protein was much less stable than rhTRIM5alpha, and this
      difference correlated with higher self-ubiquitination activity. Using a
      stabilized form of huTRIM5alpha in which the steady-state expression level was
      more similar to rhTRIM5alpha, we observed comparable HIV-1 restriction activity
      in multi-round HIV-1 challenge assays. Lastly, primary human CD4 T cells
      expressing a stabilized huTRIM5alpha were protected from HIV-1-mediated
      destruction in vivo, indicating that efforts to stabilize huTRIM5alpha should
      have significant long-term therapeutic value. 

PMID- 24662948
TI  - Species composition, distribution and habitat types of Odonata in the
      iSimangaliso Wetland Park, KwaZulu-Natal, South Africa and the associated
      conservation implications.
AB  - Maputaland-Pondoland-Albany, South Africa has been identified as a biodiversity
      hotspot and centre for endemism. Odonata make good indicators of freshwater
      ecosystem health. Consequently we compiled a list of Odonata species recorded to
      date in the iSimangaliso Wetland Park. We then detailed important species in
      terms of endemism, conservation status, and potential as indicator species.
      Finally, we compared Odonata assemblages of different sites sampled within the
      park to illustrate habitat importance. Species identified during two formal
      surveys and incidental observations made during the study period were combined
      with an existing database to compile an accurate and up to date species list for
      the iSimangaliso Wetland Park. Data from this study were then analyzed to
      determine which water bodies had the most similar species composition. The
      Dragonfly Biotic Index (DBI) value of each study area was also determined. We
      recorded 68 odonate species in the iSimangaliso Wetland Park, adding 13 species
      to the Ezemvelo KwaZulu-Natal Wildlife database for the area. This brings the
      total number of Odonata species for the iSimangaliso Wetland Park to 86. Eight
      species are red-listed, 12 are restricted in South Africa to the coastal plains
      of northern KwaZulu-Natal, and the remainder occurs widely across the southern
      African savanna. Analyses indicate that species odonate assemblages were most
      similar in water bodies with comparable habitats. iSimangaliso Wetland Park is
      identified as an important area for Odonata diversity and endemism, a trend also
      reflected by the DBI values. Shifts in the existing species assemblages would
      indicate changes within the ecosystem and thus this species account provides
      necessary baseline data for the area. Species Conservation efforts should thus
      target water bodies of varying habitat types to protect greater species
      diversity. 

PMID- 24662947
TI  - Multicenter randomized phase 2 clinical trial of a recombinant human endostatin
      adenovirus in patients with advanced head and neck carcinoma.
AB  - A randomized, open-label, phase 2, multicenter clinical trial was conducted to
      evaluate the efficacy and safety of the addition of a recombinant human
      endostatin adenovirus (E10A) to cisplatin and paclitaxel in patients with
      advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma.
      Patients with locally advanced or metastatic head and neck squamous cell
      carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy
      were randomly assigned to receive E10A plus chemotherapy every 3 weeks for a
      maximum of six cycles or to receive chemotherapy only. One hundred and thirty-six
      eligible patients were randomly assigned. The addition of E10A did not
      significantly improve the objective response rate (29.9 versus 39.7%, P = 0.154).
      However, patients who received endostatin had longer progression-free survival
      (7.03 versus 3.60 months, P = 0.006; hazard ratio: 0.55). The combination of E10A
      with chemotherapy benefited prior chemotherapy-treated patients and those who
      received three to four treatment cycles (6.50 versus 3.43 months, P = 0.003; 8.27
      versus 4.27 months, P = 0.018; respectively). The overall disease control rate
      significantly increased from 80.6% in the control group to 92.6% in the test
      group (P = 0.034). Except for fever, no adverse events were associated with the
      E10A treatment. In summary, E10A plus chemotherapy is a safe and effective
      therapeutic approach in patients with advanced head and neck squamous cell
      carcinoma or nasopharyngeal carcinoma. 

PMID- 24662942
TI  - Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific
      disease burden in a set of 88 countries.
AB  - BACKGROUND: Toxoplasmosis is becoming a global health hazard as it infects 30-50%
      of the world human population. Clinically, the life-long presence of the parasite
      in tissues of a majority of infected individuals is usually considered
      asymptomatic. However, a number of studies show that this 'asymptomatic
      infection' may also lead to development of other human pathologies. AIMS OF THE
      STUDY: The purpose of the study was to collect available geoepidemiological data
      on seroprevalence of toxoplasmosis and search for its relationship with mortality
      and disability rates in different countries. METHODS AND FINDINGS: Prevalence
      data published between 1995-2008 for women in child-bearing age were collected
      for 88 countries (29 European). The association between prevalence of
      toxoplasmosis and specific disease burden estimated with age-standardized
      Disability Adjusted Life Year (DALY) or with mortality, was calculated using
      General Linear Method with Gross Domestic Product per capita (GDP), geolatitude
      and humidity as covariates, and also using nonparametric partial Kendall
      correlation test with GDP as a covariate. The prevalence of toxoplasmosis
      correlated with specific disease burden in particular countries explaining 23% of
      variability in disease burden in Europe. The analyses revealed that for example,
      DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed
      correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and
      another 12 diseases showed positive trends (p<0.1). For several obtained
      significant correlations between the seroprevalence of toxoplasmosis and specific
      diseases/clinical entities, possible pathophysiological, biochemical and
      molecular explanations are presented. CONCLUSIONS: The seroprevalence of
      toxoplasmosis correlated with various disease burden. Statistical associations
      does not necessarily mean causality. The precautionary principle suggests however
      that possible role of toxoplasmosis as a triggering factor responsible for
      development of several clinical entities deserves much more attention and
      financial support both in everyday medical practice and future clinical research.

PMID- 24662949
TI  - Carvedilol protects against iron-induced microparticle generation and apoptosis
      of endothelial cells.
AB  - BACKGROUND: Increased circulating endothelial microparticles (EMPs) have been
      shown to associate with endothelial dysfunction. We explored the effect of iron
      on EMP generation by human umbilical vein endothelial cells (HUVECs) and the
      potential protective effect of carvedilol. METHODS: FeCl 3 was added to HUVEC
      culture. Iron entry into cells was monitored using fluorescent microscopic
      imaging, while the quantity of EMPs that was released was determined by flow
      cytometry. The apoptosis of HUVECs was assessed by annexin V/propidium iodide
      assay and caspase-3 expression. Membrane bleb formation was visualized using
      electron microscopy. Intracellular production of reactive oxygen species (ROS)
      was also monitored. The effects of beta-blockers, carvedilol and propranolol on
      these processes were determined by co-incubation in a dose-dependent manner. Iron
      entry into HUVECs was not blocked by either beta-blocker. Iron induced the
      generation of EMPs, the formation of membrane blebs, the apoptosis of HUVECs and
      the production of ROS, each in a dose-dependent manner. Carvedilol, but not
      propranolol, ameliorated all of these processes. RESULTS: Our result indicates
      that iron induces EMP generation and apoptosis of endothelial cells in
      association with increased oxidative stress. CONCLUSION: The protective effects
      of carvedilol, via its antioxidant effect, may have therapeutic potential in
      patients with iron overload.

PMID- 24662950
TI  - Continued spirometry changes after cessation of exposure in asbestos-cement
      workers.
AB  - OBJECTIVE: To assess further progression of spirometry parameters among former
      asbestos-cement plant workers. METHODS: The following parameters were assessed:
      forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the
      ratio (FEV1/FVC) using a linear regression model with mixed effects. RESULTS: The
      analysis included 3005 individuals. Spirometrically defined restrictive
      ventilatory defects were registered in 21.6% of the patients, obstructive defects
      in 8.3%, whereas mixed changes in 7%. Current smokers had significantly lower
      levels of FEV1, FVC, and FEV1/FVC and a steeper decline compared with nonsmokers.
      More rapid progression was also observed along with increasing termination of
      exposure. Having higher exposure was associated with a slower decline in FEV1 and
      FEV1/FVC ratios. CONCLUSIONS: This report indicates that asbestos-cement workers
      with higher cumulative exposure still had lower mean levels of spirometric
      parameters, despite cessation of asbestos exposure many years ago.

PMID- 24662951
TI  - Poor Asthma control among US workers: health-related quality of life, work
      impairment, and health care use.
AB  - OBJECTIVE: This study examined the impact of asthma control on health-related
      outcomes among employed US asthma sufferers treated with prescription medicines.
      METHODS: Data from the 2011 National Health and Wellness Survey (N = 75,000) were
      used. The Asthma Control Test, validated measures of health-related quality of
      life, work productivity and activity impairment, and questions assessing health
      care use were included. RESULTS: Of the 2026 employed asthma sufferers treated
      with prescription medicines included, 39.7% had Asthma Control Test scores
      indicating poorly controlled asthma. After adjusting for covariates, workers with
      poorly controlled asthma had worse health-related quality of life, work and
      activity impairment, and more health care use than those with well-controlled
      asthma. CONCLUSIONS: Poorly controlled asthma in employed patients treated with
      prescription medicines is common, and associated with negative health outcomes.
      Workers, employers, and payers could all benefit from improvements in asthma
      control.

PMID- 24662952
TI  - Advantages of the net benefit regression framework for economic evaluations of
      interventions in the workplace: a case study of the cost-effectiveness of a
      collaborative mental health care program for people receiving short-term
      disability benefits for psychiatric disorders.
AB  - OBJECTIVE: Economic evaluations commonly accompany trials of new treatments or
      interventions; however, regression methods and their corresponding advantages for
      the analysis of cost-effectiveness data are not well known. METHODS: To
      illustrate regression-based economic evaluation, we present a case study
      investigating the cost-effectiveness of a collaborative mental health care
      program for people receiving short-term disability benefits for psychiatric
      disorders. We implement net benefit regression to illustrate its strengths and
      limitations. RESULTS: Net benefit regression offers a simple option for cost
      effectiveness analyses of person-level data. By placing economic evaluation in a
      regression framework, regression-based techniques can facilitate the analysis and
      provide simple solutions to commonly encountered challenges. CONCLUSIONS:
      Economic evaluations of person-level data (eg, from a clinical trial) should use
      net benefit regression to facilitate analysis and enhance results.

PMID- 24662953
TI  - Prevalence of workers with shifts in hearing by industry: a comparison of OSHA
      and NIOSH Hearing Shift Criteria.
AB  - OBJECTIVE: The purpose of this study was to compare the prevalence of workers
      with National Institute for Occupational Safety and Health significant threshold
      shifts (NSTS), Occupational Safety and Health Administration standard threshold
      shifts (OSTS), and with OSTS with age correction (OSTS-A), by industry using
      North American Industry Classification System codes. METHODS: From 2001 to 2010,
      worker audiograms were examined. Prevalence and adjusted prevalence ratios for
      NSTS were estimated by industry. NSTS, OSTS, and OSTS-A prevalences were compared
      by industry. RESULTS: Twenty percent of workers had an NSTS, 14% had an OSTS, and
      6% had an OSTS-A. For most industries, the OSTS and OSTS-A criteria identified
      28% to 36% and 66% to 74% fewer workers than the NSTS criteria, respectively.
      CONCLUSIONS: Use of NSTS criteria allowing for earlier detection of shifts in
      hearing is recommended for improved prevention of occupational hearing loss.

PMID- 24662954
TI  - Real-time rotation estimation using histograms of oriented gradients.
AB  - This paper focuses on real-time rotation estimation for model-based automated
      visual inspection. In the case of model-based inspection, spatial alignment is
      essential to distinguish visual defects from normal appearance variations.
      Defects are detected by comparing the inspected object with its spatially aligned
      ideal reference model. Rotation estimation is crucial for the inspection of
      rotationally symmetric objects where mechanical manipulation is unable to ensure
      the correct object rotation. We propose a novel method for in-plane rotation
      estimation. Rotation is estimated with an ensemble of nearest-neighbor
      estimators. Each estimator contains a spatially local representation of an object
      in a feature space for all rotation angles and is constructed with a semi
      supervised self-training approach from a set of unlabeled training images. An
      individual representation in a feature space is obtained by calculating the
      Histograms of Oriented Gradients (HOG) over a spatially local region. Each
      estimator votes separately for the estimated angle; all votes are weighted and
      accumulated. The final estimation is the angle with the most votes. The method
      was evaluated on several datasets of pharmaceutical tablets varying in size,
      shape, and color. The results show that the proposed method is superior in
      robustness with comparable speed and accuracy to previously proposed methods for
      rotation estimation of pharmaceutical tablets. Furthermore, all evaluations were
      performed with the same set of parameters, which implies that the method requires
      minimal human intervention. Despite the evaluation focused on pharmaceutical
      tablets, we consider the method useful for any application that requires robust
      real-time in-plane rotation estimation. 

PMID- 24662957
TI  - Ado-trastuzumab emtansine (Kadcyla) for HER2-positive metastatic breast cancer.

PMID- 24662955
TI  - Comparative transcriptome analysis of two races of Heterodera glycines at
      different developmental stages.
AB  - The soybean cyst nematode, Heterodera glycines, is an important pest of soybeans.
      Although resistance is available against this nematode, selection for virulent
      races can occur, allowing the nematode to overcome the resistance of cultivars.
      There are abundant field populations, however, little is known about their
      genetic diversity. In order to elucidate the differences between races, we
      investigated the transcriptional diversity within race 3 and race 4 inbred lines
      during their compatible interactions with the soybean host Zhonghuang 13. Six
      different race-enriched cDNA libraries were constructed with limited nematode
      samples collected from the three sedentary stages, parasitic J2, J3 and J4
      female, respectively. Among 689 putative race-enriched genes isolated from the
      six libraries with functional annotations, 92 were validated by quantitative RT
      PCR (qRT-PCR), including eight putative effector encoding genes. Further race
      enriched genes were validated within race 3 and race 4 during development in
      soybean roots. Gene Ontology (GO) analysis of all the race-enriched genes at J3
      and J4 female stages showed that most of them functioned in metabolic processes.
      Relative transcript level analysis of 13 selected race-enriched genes at four
      developmental stages showed that the differences in their expression abundance
      took place at either one or more developmental stages. This is the first
      investigation into the transcript diversity of H. glycines races throughout their
      sedentary stages, increasing the understanding of the genetic diversity of H.
      glycines. 

PMID- 24662958
TI  - In brief: Oxytrol OTC.

PMID- 24662959
TI  - How successful are first episode programs? A review of the evidence for
      specialized assertive early intervention.
AB  - PURPOSE OF REVIEW: It has been hypothesized that the first 5 years after first
      episode of psychosis are a critical period with opportunities for ameliorating
      the course of illness. On the basis of this rationale, specialized assertive
      early intervention services were developed. We wanted to investigate the evidence
      basis for such interventions. RECENT FINDINGS: The evidence for the effectiveness
      of specialized assertive early intervention services is mainly based on one large
      randomized clinical trial, the OPUS trial, but it is supported by the findings in
      smaller trials, such as the Lambeth Early Onset trial, the Croydon Outreach and
      Assertive Support Team trial and the Norwegian site of Optimal Treatment trial.
      There are positive effects on psychotic and negative symptoms, on substance abuse
      and user satisfaction, but the clinical effects are not sustainable when patients
      are transferred to standard treatment. However, the positive effects on service
      use and ability to live independently seem to be durable. SUMMARY: Implementation
      of specialized assertive early intervention services is recommended, but the
      evidence basis needs to be strengthened through replication in large high-quality
      trials. Recommendation regarding the duration of treatment must await results of
      ongoing trials comparing 2 years of intervention with extended treatment periods.

PMID- 24662960
TI  - Ethical issues in the use of genetic testing of patients with schizophrenia and
      their families.
AB  - PURPOSE OF REVIEW: This review outlines the positive and negative aspects of DNA
      testing and provides an account of the issues particularly relevant to
      schizophrenia. RECENT FINDINGS: Modern technology has changed the field of
      medicine so rapidly that patients and their families have become much more
      independent in their healthcare decisions than in the previous decade. Simply by
      finding information on the Internet, they gain knowledge about disease diagnosis,
      treatment options and their side-effects. No medical field likely has been more
      affected and more controversial than that of genetics. It is now possible to
      sequence the individual human genome and detect single nucleotide variations,
      microdeletions and duplications within it. Commercial companies have sprung up in
      a similar manner to the software or electronic industries and have begun to
      market direct-to-consumer DNA testing. Much of this may be performed to satisfy
      curiosity about one's ancestry; but commercially available results that appear
      incidentally can also be distributed to the consumer. SUMMARY: Ethicists,
      genetics researchers, clinicians and government agencies are currently in
      discussion about concerns raised about commercially available DNA testing, while
      at the same time recognizing its value in some instances to be able to predict
      very serious disabilities.

PMID- 24662961
TI  - Peer support and peer-led family support for persons living with schizophrenia.
AB  - PURPOSE OF REVIEW: Peer support and peer-led family psychoeducation represent two
      distinct and complementary recovery-oriented models to support individuals who
      live with schizophrenia and their families, respectively. The goals of these
      models focus on improving knowledge, coping, self-care, social support, and self
      management strategies. These models represent important capacity-building
      strategies for people who live with the illness and the people who love them.
      This brief article is intended to provide the practicing clinician, person living
      with schizophrenia, and policy maker with a working knowledge of the current
      state of the literature in these two related fields. Practitioners should
      consider these resources and integrate them into their care. A person living with
      schizophrenia could use this review to advocate for appropriate resources and to
      identify career opportunities. Policy makers could benefit from an understanding
      of the literature to mitigate financial and cultural barriers to adopting these
      practices. RECENT FINDINGS: The last 5 years have seen a dramatic expansion of
      the application of randomized controlled trials (RCTs) to give evidence to match
      the experience of people in these programs. The field has seen Wellness Recovery
      Action Plan (WRAP) named as evidence-based practice by the National Registry of
      Evidence-Based Practices. A RCT was also conducted for another peer-developed and
      led program called Building Recovery of Individual Dreams & Goals through
      Education & Support. Family to Family, the largest peer-led family
      psychoeducation course, was also found to have significant impact after the study
      and also 6 months later in RCT. Family to Family has also been named as an
      evidence-based practice. SUMMARY: The field of people who are living well with
      schizophrenia working as resources and supports to others living with the illness
      is an idea that is growing momentum. This momentum has been matched by the RCT
      evidence. Peer support as a professional role has an emerging literature that
      needs to be grown. WRAP and National Alliance on Mental Illness's Family to
      Family program are evidence-based practices and widely available. Peer support
      and peer-led family support for persons living with schizophrenia is a nascent
      field with much potential.

PMID- 24662963
TI  - Novel bone-targeting agents in prostate cancer.
AB  - Prostate cancer (PC) is the most commonly diagnosed non-skin cancer and the
      second leading cause of cancer death among American men. Bone is by far the most
      common site for metastasis. The median survival of patients from the development
      of bone metastases is ~3 years. During this period, patients are at increased
      risk of skeletal-related events (SREs) including: intractable bone pain,
      pathological fractures and spinal-cord compression. Several novel bone-targeted
      agents including bisphosphonates, receptor activator of nuclear factor kappaB
      (RANK) ligand monoclonal antibodies, endothelin receptor antagonists, bone
      seeking radioisotopes, selective estrogen receptor (ER) modulators and tyrosine
      kinase inhibitors are now available and under evaluation in clinical trials in PC
      patients with bone metastases. This review article will provide an overview of
      the multiple emerging novel bone-targeted therapies in PC.

PMID- 24662962
TI  - Effects of naproxen on immune responses in a colchicine-induced rat model of
      Alzheimer's disease.
AB  - BACKGROUND: The components of the immune system have been indicated to be linked
      with the neurotoxicity in Alzheimer's disease (AD). The participation of the
      immune system in the neurodegeneration in a rat model of colchicine-induced AD
      has not been explored. METHODS: In the present study, hippocampal
      neurodegeneration along with reactive oxygen species (ROS), nitrite and TNF-alpha
      in the hippocampus and some systemic immune responses were measured after 15 and
      21 days of intracerebroventricular colchicine injection in rats and again after
      oral administration of different doses of the anti-inflammatory drug naproxen in
      AD rats. RESULTS: Chromatolysis and amyloid plaques were found along with higher
      ROS, nitrite and TNF-alpha levels in the hippocampus of colchicine-induced AD
      rats, and these changes were prevented by naproxen in a dose-dependent manner.
      Alterations in immunological parameters [increased phagocytic activity of white
      blood cells and splenic polymorphonuclear cells (PMN), increased cytotoxicity and
      decreased leucocyte adhesive inhibition index (LAI) of splenic mononuclear cells
      (MNC)] were also observed in colchicine-injected rats, which showed a dose
      dependent recovery after oral administration of naproxen in AD rats. The number
      of plaques, chromatolysis of Nissl granules, TNF-alpha, nitrite and ROS levels in
      the hippocampus, phagocytic activity of splenic PMN and LAI of splenic MNC in AD
      rats showed greater changes in the 21- than in the 15-day study, and the recovery
      of these parameters after administration of naproxen differed between the two
      study durations. CONCLUSION: The present study shows that colchicine-induced
      neurodegeneration is time dependent and mediated by cyclooxygenase-induced
      neuroinflammation, which is reflected in the systemic immunological responses.

PMID- 24662964
TI  - Prevalence and antimicrobial resistance of Enterococcus species: a hospital-based
      study in China.
AB  - OBJECTIVE: to investigate the prevalence and antimicrobial resistance of
      Enterococcus species isolated from a university hospital, and explore the
      mechanisms underlying the antimicrobial resistance, so as to provide clinical
      evidence for the inappropriate clinical use of antimicrobial agents and the
      control and prevention of enterococcal infections. METHODS: a total of 1,157
      enterococcal strains isolated from various clinical specimens from January 2010
      to December 2012 in the General Hospital of Ningxia Medical University were
      identified to species level with a VITEK-2 COMPACT fully automated
      microbiological system, and the antimicrobial susceptibility of Enterococcus
      species was determined using the Kirby-Bauer disc diffusion method. The multiple
      drug resistant enterococcal isolates were screened from the clinical isolates of
      Enterococcus species from the burns department. The minimal inhibitory
      concentration (MIC) of Enterococcus species to the three fluoroquinolones,
      including ciprofloxacin, gatifloxacin and levofloxacin was determined with the
      agar dilution method, and the changes in the MIC of Enterococcus species to the
      three fluoroquinolones following reserpine treatment were evaluated. The beta
      lactam, aminoglycoside, tetracycline, macrolide, glycopeptide resistance genes
      and the efflux pump emeA genes were detected in the enterococcal isolates using a
      polymerase chain reaction (PCR) assay. RESULTS: the 1,157 clinical isolates of
      Enterococcus species included 679 E. faecium isolates (58.7%), 382 E. faecalis
      isolates (33%), 26 E. casseliflavus isolates (2.2%), 24 E. avium isolates (2.1%),
      and 46 isolates of other Enterococcus species (4%). The prevalence of
      antimicrobial resistance varied significantly between E. faecium and E. faecalis,
      and <= 1.1% of these two Enterococcus species were found to be resistant to
      vancomycin, teicoplanin or linezolid. In addition, the Enterococcus species
      isolated from different departments of the hospital exhibited various resistances
      to the same antimicrobial agent, while reserpine treatment reduced the resistance
      of Enterococcus species to ciprofloxacin, gatifloxacin and levofloxacin. The beta
      lactamase gene TEM, aminoglycoside-modifying-enzyme genes aac(6')-aph(2"),
      aph(3')-III, ant(6)-I and ant(2")-I, tetracycline resistance gene tetM,
      erythromycin resistance gene ermB, vancomycin resistance gene vanA and the
      enterococcal multidrug resistance efflux emeA gene were detected in 77%, 62%,
      26%, 13%, 36%, 31%, 66%, 5% and 55% of the 100 multiple-drug resistant
      enterococcal isolates. CONCLUSIONS: similar to previous findings, E. faecium and
      E. faecalis are predominant conditionally pathogenic bacteria that cause hospital
      acquired infections that can cause urinary and respiratory system infections.
      Multiple and high-level antimicrobial resistance is highly prevalent in the
      hospital isolates of Enterococcus species. Reserpine treatment inhibits the
      active efflux of Enterococcus species to ciprofloxacin, gatifloxacin and
      levofloxacin in vitro and reduces the MIC of Enterococcus species to these three
      fluoroquinolones. The presence of the enterococcal multidrug resistance efflux
      emeA gene is associated with the resistance to antibiotics in Enterococcus
      species. The monitoring of the prevalence and antimicrobial resistance of
      Enterococcus species is of great significance to guide the control and prevention
      of enterococcal infections.

PMID- 24662965
TI  - Ecological factors and adolescent marijuana use: results of a prospective study
      in Santiago, Chile.
AB  - PURPOSE: Despite the growing evidence that ecological factors contribute to
      substance use, the relationship of ecological factors and illicit drugs such as
      marijuana use is not well understood, particularly among adolescents in Latin
      America. Guided by social disorganization and social stress theories, we
      prospectively examined the association of disaggregated neighborhood
      characteristics with marijuana use among adolescents in Santiago, Chile, and
      tested if these relationships varied by sex. METHODS: Data for this study are
      from 725 community-dwelling adolescents participating in the Santiago
      Longitudinal Study, a study of substance using behaviors among urban adolescents
      in Santiago, Chile. Adolescents completed a two-hour interviewer administered
      questionnaire with questions about drug use and factors related to drug using
      behaviors. RESULTS: As the neighborhood levels of drug availability at baseline
      increased, but not crime or noxious environment, adolescents had higher odds of
      occasions of marijuana use at follow up, approximately 2 years later (odds ratio
      [OR] = 1.39; 95% CI = 1.16-1.66), even after controlling for the study's
      covariates. No interactions by sex were significant. DISCUSSION: The findings
      suggest that "poverty", "crime", and "drug problems" may not be synonyms and thus
      can be understood discretely. As Latin American countries re-examine their drug
      policies, especially those concerning decriminalizing marijuana use, the findings
      suggest that attempts to reduce adolescent marijuana use in disadvantaged
      neighborhoods may do best if efforts are concentrated on specific features of the
      "substance abuse environment".

PMID- 24662966
TI  - Exposure to neighborhood green space and mental health: evidence from the survey
      of the health of Wisconsin.
AB  - Green space is now widely viewed as a health-promoting characteristic of
      residential environments, and has been linked to mental health benefits such as
      recovery from mental fatigue and reduced stress, particularly through
      experimental work in environmental psychology. Few population level studies have
      examined the relationships between green space and mental health. Further, few
      studies have considered the role of green space in non-urban settings. This study
      contributes a population-level perspective from the United States to examine the
      relationship between environmental green space and mental health outcomes in a
      study area that includes a spectrum of urban to rural environments. Multivariate
      survey regression analyses examine the association between green space and mental
      health using the unique, population-based Survey of the Health of Wisconsin
      database. Analyses were adjusted for length of residence in the neighborhood to
      reduce the impact of neighborhood selection bias. Higher levels of neighborhood
      green space were associated with significantly lower levels of symptomology for
      depression, anxiety and stress, after controlling for a wide range of confounding
      factors. Results suggest that "greening" could be a potential population mental
      health improvement strategy in the United States. 

PMID- 24662967
TI  - Experimental demonstration of reservoir computing on a silicon photonics chip.
AB  - In today's age, companies employ machine learning to extract information from
      large quantities of data. One of those techniques, reservoir computing (RC), is a
      decade old and has achieved state-of-the-art performance for processing
      sequential data. Dedicated hardware realizations of RC could enable speed gains
      and power savings. Here we propose the first integrated passive silicon photonics
      reservoir. We demonstrate experimentally and through simulations that, thanks to
      the RC paradigm, this generic chip can be used to perform arbitrary Boolean logic
      operations with memory as well as 5-bit header recognition up to 12.5 Gbit s(-1),
      without power consumption in the reservoir. It can also perform isolated spoken
      digit recognition. Our realization exploits optical phase for computing. It is
      scalable to larger networks and much higher bitrates, up to speeds >100 Gbit s(
      1). These results pave the way for the application of integrated photonic RC for
      a wide range of applications. 

PMID- 24662968
TI  - Fast tuning of double Fano resonance using a phase-change metamaterial under low
      power intensity.
AB  - In this work, we numerically demonstrate an all-optical tunable Fano resonance in
      a fishnet metamaterial(MM) based on a metal/phase-change material(PCM)/metal
      multilayer. We show that the displacement of the elliptical nanoholes from their
      centers can split the single Fano resonance (FR) into a double FR, exhibiting
      higher quality factors. The tri-layer fishnet MMs with broken symmetry
      accomplishes a wide tuning range in the mid-infrared(M-IR) regime by switching
      between the amorphous and crystalline states of the PCM (Ge2Sb2Te5). A
      photothermal model is used to study the temporal variation of the temperature of
      the Ge2Sb2Te5 film to show the potential for switching the phase of Ge2Sb2Te5 by
      optical heating. Generation of the tunable double FR in this asymmetric structure
      presents clear advantages as it possesses a fast tuning time of 0.36 ns, a low
      pump light intensity of 9.6 MUW/MUm(2), and a large tunable wavelength range
      between 2124 nm and 3028 nm. The optically fast tuning of double FRs using phase
      change metamaterials(PCMMs) may have potential applications in active multiple
      wavelength nanodevices in the M-IR region.

PMID- 24662969
TI  - Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome
      integrity are linked to telomere function.
AB  - The short arms of the ten acrocentric human chromosomes share several repetitive
      DNAs, including ribosomal RNA genes (rDNA). The rDNA arrays correspond to
      nucleolar organizing regions that coalesce each cell cycle to form the nucleolus.
      Telomere disruption by expressing a mutant version of telomere binding protein
      TRF2 (dnTRF2) causes non-random acrocentric fusions, as well as large-scale
      nucleolar defects. The mechanisms responsible for acrocentric chromosome
      sensitivity to dysfunctional telomeres are unclear. In this study, we show that
      TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are
      crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal
      changes occur. We used the controllable dnTRF2 system to precisely dissect the
      timing and progression of nucleolar and chromosomal instability induced by
      telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage
      and morphological changes that occur at acrocentric short arms. The rDNA repeat
      arrays on the short arms decondense, and are coated by RNA polymerase I
      transcription binding factor UBF, physically linking acrocentrics to one another
      as they become fusogenic. These results highlight the importance of telomere
      function in nucleolar stability and structural integrity of acrocentric
      chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to
      cause DNA damage at chromosome ends, but our findings suggest that it also
      disrupts chromosome structure beyond the telomere region, specifically within the
      rDNA arrays located on acrocentric chromosomes. These results have relevance for
      Robertsonian translocation formation in humans and mechanisms by which
      acrocentric-acrocentric fusions are promoted by DNA damage and repair. 

PMID- 24662970
TI  - Influence of glycosylation pattern on the molecular properties of monoclonal
      antibodies.
AB  - Glycosylation is an important post-translational modification during protein
      production in eukaryotic cells, and it is essential for protein structure,
      stability, half-life, and biological functions. In this study, we produced
      various monoclonal antibody (mAb) glycoforms from Chinese hamster ovary (CHO)
      cells, including the natively glycosylated antibody, the enriched G0 form, the
      deglycosylated form, the afucosylated form, and the high mannose form, and we
      compared their intrinsic properties, side-by-side, through biophysical and
      biochemical approaches. Spectroscopic analysis indicates no measureable secondary
      or tertiary structural changes after in vitro or in vivo modification of the
      glycosylation pattern. Thermal unfolding experiments show that the high mannose
      and deglycosylated forms have reduced thermal stability of the CH2 domain
      compared with the other tested glycoforms. We also observed that the individual
      domain's thermal stability could be pH dependent. Proteolysis analysis indicates
      that glycosylation plays an important role in stabilizing mAbs against proteases.
      The stability of antibody glycoforms at the storage condition (2-8  degrees C)
      and at accelerated conditions (30 and 40  degrees C) was evaluated, and the
      results indicate that glycosylation patterns do not substantially affect the
      storage stability of the antibody we studied. 

PMID- 24662971
TI  - Helicobacter pylori protects oncogenically transformed cells from reactive oxygen
      species-mediated intercellular induction of apoptosis.
AB  - Malignant transformation of gastric epithelial cells by chronic Helicobacter
      pylori infection is caused by several mechanisms including attraction of reactive
      oxygen species (ROS)-producing neutrophils and cytotoxin-associated antigen A
      mediated dysplastic alterations. Here we show that H.pylori protects transformed
      cells from ROS-mediated intercellular induction of apoptosis. This potential
      control step in oncogenesis depends on the HOCl and NO/peroxynitrite (PON)
      signaling pathways. Helicobacter pylori-associated catalase and superoxide
      dismutase (SOD) efficiently cooperate in the inhibition of HOCl and the NO/PON
      signaling pathways. Helicobacter pylori catalase prevents HOCl synthesis through
      decomposition of hydrogen peroxide. Helicobacter pylori-associated SOD interferes
      with the crucial interactions between superoxide anions and HOCl, as well as
      superoxide anions and NO. The ratio of bacteria to malignant cells is critical
      for sufficient protection of transformed cells. Low concentrations of H.pylori
      more efficiently inhibited ROS-mediated destruction of transformed cells when
      compared with high concentrations of bacteria. Our data demonstrate the critical
      role of H.pylori antioxidant enzymes in the survival of transformed cells,
      modulating an early step of oncogenesis that is distinct from the transformation
      process per se.

PMID- 24662973
TI  - Comparison of potential risks between intracranial and extracranial vertebral
      artery dissections.
AB  - BACKGROUND/AIMS: To better understand potential risks for vertebral artery (VA)
      dissection (VAD), we compared intracranial and extracranial VADs. METHODS: We
      analyzed consecutively admitted VAD patients over a 9-year period in whom VAD was
      confirmed by angiography. All patients were categorized as having intracranial or
      extracranial VAD, and demographic and radiological characteristics of VAD were
      compared. We used multivariate analysis to predict the risks for intracranial and
      extracranial VADs. RESULTS: The study population (n = 74) had a mean age of 46.0
      +/- 10.3 years. VAD was more frequent in the nondominant VA (n = 49,
      66.2%).Vertical nidus of VAD was more common in the intracranial segment (81.1%),
      and more particularly it was most frequently located within a 2-mm perimeter of
      the posterior inferior cerebellar artery (PICA) orifice (60.0%). Absence of
      traumatic history (OR 13.1, 95% CI 1.6-107.4; p = 0.016), history of hypertension
      (OR 14.1, 95% CI 1.1-184.6; p = 0.043)and aging (OR 1.1 per 1-year increase, 95%
      CI 1.0-1.2; p =0.038) were independent predictors of intracranial VAD.
      CONCLUSION: As compared to extracranial VAD, intracranial VAD was particularly
      frequent and particularly vulnerable at the perimeters of the PICA and
      nondominant VA and was associated with an absent trauma history, hypertension and
      aging. Formation of VAD appeared to be different according to intracranial or
      extracranial involvement.

PMID- 24662975
TI  - Perampanel (Fycompa) for epilepsy.

PMID- 24662972
TI  - Genome-wide interaction study of smoking and bladder cancer risk.
AB  - Bladder cancer is a complex disease with known environmental and genetic risk
      factors. We performed a genome-wide interaction study (GWAS) of smoking and
      bladder cancer risk based on primary scan data from 3002 cases and 4411 controls
      from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were
      used to evaluate both additive and multiplicative interactions between individual
      single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with
      interaction P values < 5 * 10(-) (5) were evaluated further in an independent
      dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs
      that showed association in a consistent manner with the initial dataset and in
      the combined dataset, providing evidence of interaction with tobacco use.
      Further, two of these novel SNPs showed strong evidence of association with
      bladder cancer in tobacco use subgroups that approached genome-wide significance.
      Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never
      smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20
      1.50, P value = 5.18 * 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was
      a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P
      value = 6.35 * 10(-) (7)). In our analysis of smoking and bladder cancer, the
      tests for multiplicative interaction seemed to more commonly identify
      susceptibility loci with associations in never smokers, whereas the additive
      interaction analysis identified more loci with associations among smokers
      including the known smoking and NAT2 acetylation interaction. Our findings
      provide additional evidence of gene-environment interactions for tobacco and
      bladder cancer. 

PMID- 24662974
TI  - Mechanisms relevant to the enhanced virulence of a dihydroxynaphthalene-melanin
      metabolically engineered entomopathogen.
AB  - The entomopathogenic fungus Metarhizium anisopliae MA05-169 is a transformant
      strain that has been metabolically engineered to express dihydroxynaphthalene
      melanin biosynthesis genes. In contrast to the wild type strain, the transformant
      displays a greater resistance to environmental stress and a higher virulence
      toward target insect host. However, the underlying mechanisms for these
      characteristics remain unclear; hence experiments were initiated to explore the
      possible mechanism(s) through physiological and molecular approaches. Although
      both transformant and wild type strains could infect and share the same insect
      host range, the former germinated faster and produced more appressoria than the
      latter, both in vivo and in vitro. The transformant showed a significantly
      shorter median lethal time (LT50) when infecting the diamondback moth (Plutella
      xylostella) and the striped flea beetle (Phyllotreta striolata), than the wild
      type. Additionally, the transformant was more tolerant to reactive oxygen species
      (ROS), produced 40-fold more orthosporin and notably overexpressed the
      transcripts of the pathogenicity-relevant hydrolytic enzymes (chitinase,
      protease, and phospholipase) genes in vivo. In contrast, appressorium turgor
      pressure and destruxin A content were slightly decreased compared to the wild
      type. The transformant's high anti-stress tolerance, its high virulence against
      five important insect pests (cowpea aphid Aphis craccivora, diamondback moth Pl.
      xylostella, striped flea beetle Ph. striolata, and silverleaf whitefly Bemisia
      argentifolii) and its capacity to colonize the root system are key properties for
      its potential bio-control field application. 

PMID- 24662976
TI  - Certolizumab pegol (Cimzia) and ustekinumab (Stelara) for psoriatic arthritis.

PMID- 24662977
TI  - In brief: rosiglitazone (Avandia) unbound.

PMID- 24662978
TI  - A designed experiments approach to optimization of automated data acquisition
      during characterization of bacteria with MALDI-TOF mass spectrometry.
AB  - MALDI-TOF MS has been shown capable of rapidly and accurately characterizing
      bacteria. Highly reproducible spectra are required to ensure reliable
      characterization. Prior work has shown that spectra acquired manually can have
      higher reproducibility than those acquired automatically. For this reason, the
      objective of this study was to optimize automated data acquisition to yield
      spectra with reproducibility comparable to those acquired manually. Fractional
      factorial design was used to design experiments for robust optimization of
      settings, in which values of five parameters (peak selection mass range, signal
      to noise ratio (S:N), base peak intensity, minimum resolution and number of shots
      summed) commonly used to facilitate automated data acquisition were varied.
      Pseudomonas aeruginosa was used as a model bacterium in the designed experiments,
      and spectra were acquired using an intact cell sample preparation method. Optimum
      automated data acquisition settings (i.e., those settings yielding the highest
      reproducibility of replicate mass spectra) were obtained based on statistical
      analysis of spectra of P. aeruginosa. Finally, spectrum quality and
      reproducibility obtained from non-optimized and optimized automated data
      acquisition settings were compared for P. aeruginosa, as well as for two other
      bacteria, Klebsiella pneumoniae and Serratia marcescens. Results indicated that
      reproducibility increased from 90% to 97% (p-value[Formula: see text]0.002) for
      P. aeruginosa when more shots were summed and, interestingly, decreased from 95%
      to 92% (p-value [Formula: see text] 0.013) with increased threshold minimum
      resolution. With regard to spectrum quality, highly reproducible spectra were
      more likely to have high spectrum quality as measured by several quality metrics,
      except for base peak resolution. Interaction plots suggest that, in cases of low
      threshold minimum resolution, high reproducibility can be achieved with fewer
      shots. Optimization yielded more reproducible spectra than non-optimized settings
      for all three bacteria. 

PMID- 24662980
TI  - A unified strategy for the synthesis of highly oxygenated diaryl ethers featured
      in ellagitannins.
AB  - Ellagitannins are a family of polyphenols containing more than 1,000 natural
      products. Nearly 40% of these compounds contain a highly oxygenated diaryl ether
      that is one of the most critical elements to their structural diversity. Here, we
      report a unified strategy for the synthesis of highly oxygenated diaryl ethers
      featured in ellagitannins. The strategy involves oxa-Michael addition of phenols
      to an orthoquinone building block, with subsequent elimination and reductive
      aromatization. The design of the building block--a halogenated orthoquinone
      monoketal of gallal--reduces the usual instability of orthoquinone and controls
      addition/elimination. Reductive aromatization is achieved with perfect
      chemoselectivity in the presence of other reducible functional groups. This
      strategy enables the synthesis of different diaryl ethers. The first total
      synthesis of a natural ellagitannin bearing a diaryl ethers is performed to
      demonstrate that the strategy increases the number of synthetically available
      ellagitannins.

PMID- 24662979
TI  - Chemokine CXCL8 promotes HIV-1 replication in human monocyte-derived macrophages
      and primary microglia via nuclear factor-kappaB pathway.
AB  - BACKGROUND: Chemokine CXCL8 is an important neutrophil chemoattractant implicated
      in various neurodegenerative disorders. Cytokine/chemokine imbalance, with an
      increase in proinflammatory cytokines like interleukin-1beta and tumor necrosis
      factor-alpha within the central nervous system, is a hallmark of human
      immunodeficiency virus (HIV)-1 infection. We previously reported that HIV-1
      infection is linked to upregulation of CXCL8 in brain tissues and human
      astrocytes. Chemokines play crucial roles in trafficking of leukocytes and
      trafficking of HIV-1-infected across the blood-brain barrier play an important
      role in HIV-1 central nervous system disease. In the post-antiretroviral therapy
      era, low level of productive replication of HIV-1 in brain is a critical
      component of neuropathogenesis regulation. The present study investigated the
      effect of CXCL8 on productive infection of HIV-1 in human monocytes-derived
      macrophages (MDM) and primary human microglia. RESULTS: Human MDM and microglia
      were infected with the blood or brain derived HIV-1 isolates, HIV-1ADA or HIV
      1JRFL. Treatment with CXCL8 significantly upregulated HIV-1p24 levels in
      supernatants of both HIV-1-infected MDM as well as microglia. In addition, the
      formation of 2-long terminal repeat (LTR) circles, a measure of viral genome
      integration, was significantly higher in CXCL8-treated, HIV-1-infected MDM and
      microglia. Transient transfection of U937 cells with HIV-1 LTR luciferase
      reporter construct resulted in increased promoter activity when treated with
      CXCL8. Moreover, increased nuclear translocation of nuclear factor-kappaB was
      seen in HIV-1-infected MDM following CXCL8 treatment. Blocking CXCL8 receptors
      CXCR1 and CXCR2 abrogated the CXCL8-mediated enhanced HIV-1 replication.
      CONCLUSION: Our results show that CXCL8 mediates productive infection of HIV-1 in
      MDM and microglia via receptors CXCR1 and CXCR2. These results demonstrate that
      CXCL8 exerts its downstream effects by increasing translocation of nuclear factor
      kappaB into the nucleus, thereby promoting HIV-1 LTR activity.

PMID- 24662982
TI  - Lupus nephritis: update on mechanisms of systemic autoimmunity and kidney
      immunopathology.
AB  - PURPOSE OF REVIEW: Traditionally, lupus nephritis has been considered an
      autoimmune disorder of unknown origin and a complex pathophysiology, but in
      recent years, its pathogenesis has been unraveled. RECENT FINDINGS: In
      individuals with unfortunate combinations of gene variants, environmental
      triggers such as certain drugs or viral infections allow autoimmunization against
      nuclear antigens, as evident by the presence of antinuclear antibodies. The
      expansion of autoreactive lymphocyte clones is driven by the nucleic acid
      component of nuclear particles from netting neutrophils and other dying cells as
      these activate immunity via viral nucleic acid-specific Toll-like receptors in
      dendritic cells and B cells. This process triggers interferon-alpha signaling
      related antiviral immunity; hence, lupus symptoms are often indistinguishable
      from those of viral infections. Inside the kidney, lupus autoantibodies bind
      several autoantigens and trigger injury and inflammation, either in the mesangium
      (classes I/II), or along both sides of the glomerular basement membrane (classes
      III/IV/V). In addition, vascular and tubulointerstitial inflammation contribute
      to the immunopathology of lupus nephritis. SUMMARY: Eventually, a better
      understanding of lupus nephritis pathogenesis will allow the identification of
      therapeutic targets that will prove effective not only in animal models but also
      in randomized clinical trials.

PMID- 24662981
TI  - CypA, a gene downstream of HIF-1alpha, promotes the development of PDAC.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a highly important transcription
      factor involved in cell metabolism. HIF-1alpha promotes glycolysis and inhibits
      of mitochondrial respiration in pancreatic ductal adenocarcinoma (PDAC). In
      response to tumor hypoxia, cyclophilin A (CypA) is over-expressed in various
      cancer types, and is associated with cell apoptosis, tumor invasion, metastasis,
      and chemoresistance in PDAC. In this study, we showed that both HIF-1alpha and
      CypA expression were significantly associated with lymph node metastasis and
      tumor stage. The expression of CypA was correlated with HIF-1alpha. Moreover, the
      mRNA and protein expression of CypA markedly decreased or increased following the
      suppression or over-expression of HIF-1alpha in vitro. Chromatin
      immunoprecipitation analysis showed that HIF-1alpha could directly bind to the
      hypoxia response element (HRE) in the CypA promoter regions and regulated CypA
      expression. Consistent with other studies, HIF-1alpha and CypA promoted PDAC cell
      proliferation and invasion, and suppressed apoptosis in vitro. Furthermore, we
      proved the combination effect of 2-methoxyestradiol and cyclosporin A both in
      vitro and in vivo. These results suggested that,CypA, a gene downstream of HIF
      1alpha, could promote the development of PDAC. Thus, CypA might serve as a
      potential therapeutic target for PDAC. 

PMID- 24662983
TI  - Early-invasive strategies for the management of coronary heart disease in chronic
      kidney disease: is acute kidney injury a consideration?
AB  - PURPOSE OF REVIEW: People with chronic kidney disease (CKD) are less likely to
      receive early-invasive management of acute coronary syndrome (ACS). The purpose
      of this article is to review the risks and outcomes of early-invasive versus
      conservative strategies, and to consider how contrast-induced acute kidney injury
      (CI-AKI) should factor in treatment decisions for people with CKD. RECENT
      FINDINGS: Numerous observational studies have characterized the prognostic
      importance of CI-AKI. However, recent studies illustrate that compared to the
      risk of AKI in individuals treated conservatively, the additional risk of kidney
      injury associated with invasive coronary procedures is relatively modest. Despite
      the risk of CI-AKI, early-invasive management of ACS has been associated with
      important long-term benefits. SUMMARY: These findings illustrate that the
      additional short-term risk of AKI associated with invasive management should be
      considered alongside long-term treatment effects on other clinical outcomes and
      should not act as a deterrent to their use. Strategies to increase the uptake of
      an invasive management approach, accompanied by the use of CI-AKI prevention
      strategies, could benefit high-risk individuals with CKD.

PMID- 24662984
TI  - Disparities in the burden, outcomes, and care of chronic kidney disease.
AB  - PURPOSE OF REVIEW: Racial, ethnic and socioeconomic disparities in chronic kidney
      disease (CKD) have been documented for decades, yet little progress has been made
      in mitigating them. Several recent studies offer new insights into the root
      causes of these disparities, point to areas in which future research is
      warranted, and identify opportunities for changes in policy and clinical
      practice. RECENT FINDINGS: Recently published evidence suggests that geographic
      disparities in CKD prevalence exist and vary by race. CKD progression is more
      rapid for racial and ethnic minority groups compared with whites and may be
      largely, but not completely, explained by genetic factors. Stark socioeconomic
      disparities in outcomes for dialysis patients exist and vary by race, place of
      residence, and treatment facility. Disparities in access to living kidney
      donation may be driven primarily by the socioeconomic status of the donor as
      opposed to recipient factors. SUMMARY: Recent studies highlight opportunities to
      eliminate disparities in CKD, including efforts to direct resources to areas and
      populations where disparities are most prevalent, efforts to understand how to
      best use emerging information on the contribution of genetic factors to
      disparities, and continued work to identify modifiable environmental, social, and
      behavioral factors for targeted interventions among high-risk populations.

PMID- 24662985
TI  - Structure of the substrate-binding b' domain of the Protein Disulfide Isomerase
      Like protein of the Testis.
AB  - Protein Disulfide Isomerase-Like protein of the Testis (PDILT) is a testis
      specific member of the PDI family. PDILT displays similar domain architecture to
      PDIA1, the founding member of this protein family, but lacks catalytic cysteines
      needed for oxidoreduction reactions. This suggests special importance of
      chaperone activity of PDILT, but how it recognizes misfolded protein substrates
      is unknown. Here, we report the high-resolution crystal structure of the b'
      domain of human PDILT. The structure reveals a conserved hydrophobic pocket,
      which is likely a principal substrate-binding site in PDILT. In the crystal, this
      pocket is occupied by side chains of tyrosine and tryptophan residues from
      another PDILT molecule, suggesting a preference for binding exposed aromatic
      residues in protein substrates. The lack of interaction of the b' domain with the
      P-domains of calreticulin-3 and calmegin hints at a novel way of interaction
      between testis-specific lectin chaperones and PDILT. Further studies of this
      recently discovered PDI member would help to understand the important role that
      PDILT plays in the differentiation and maturation of spermatozoids. 

PMID- 24662986
TI  - Survival of multiple myeloma patients aged 65-70 years in the era of novel agents
      and autologous stem cell transplantation. A multicenter retrospective
      collaborative study of the Japanese Society of Myeloma and the European Myeloma
      Network.
AB  - Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically
      changed the treatment paradigm of multiple myeloma (MM). However, it is not clear
      whether these agents improve the prognosis of elderly patients who have undergone
      autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the
      outcome of 318 newly diagnosed patients aged 65-70 years who were treated between
      January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were
      treated with conventional chemotherapy,88 with novel agent-containing regimens,
      21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel
      agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8
      and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62,
      63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto
      SCT (p < 0.02) significantly improved OS compared with the group without these
      treatment modalities. Salvage therapy with novel agents also significantly
      improved survival after relapse compared with conventional chemotherapy alone (p
      < 0.04). In a multivariate analysis, the use of novel agents was an independent
      prognostic factor significantly associated with extended OS(p < 0.003). These
      results indicate that novel agents and auto-SCT had a major impact on OS in
      eligible patients in this subgroup of MM.

PMID- 24662987
TI  - Time-lapse imaging as a tool to investigate contractility of the epididymal duct-
      effects of cGMP signaling.
AB  - The well orchestrated function of epididymal smooth muscle cells ensures transit
      of spermatozoa through the epididymal duct during which spermatozoa acquire
      motility and fertilizing capacity. Relaxation of smooth muscle cells is mediated
      by cGMP signaling and components of this pathway are found within the male
      reproductive tract. Whereas contractile function of caudal parts of the rat
      epididymal duct can be examined in organ bath studies, caput and corpus regions
      are fragile and make it difficult to mount them in an organ bath. We developed an
      ex vivo time-lapse imaging-based approach to investigate the contractile pattern
      in these parts of the epididymal duct. Collagen-embedding allowed immobilization
      without impeding contractility or diffusion of drugs towards the duct and
      therefore facilitated subsequent movie analyses. The contractile pattern was made
      visible by placing virtual sections through the acquired image stack to track
      wall movements over time. By this, simultaneous evaluation of contractile
      activity at different positions of the observed duct segment was possible. With
      each contraction translating into a spike, drug-induced alterations in
      contraction frequency could be assessed easily. Peristaltic contractions were
      also detectable and throughout all regions in the proximal epididymis we found
      regular spontaneous contractile activity that elicited movement of intraluminal
      contents. Stimulating cGMP production by natriuretic peptide ANP or inhibiting
      degradation of cGMP by the phosphodiesterase 5 inhibitor sildenafil significantly
      reduced contractile frequency in isolated duct segments from caput and corpus. RT
      PCR analysis after laser-capture microdissection localized the corresponding
      molecules to the smooth muscle layer of the duct. Our time-lapse imaging approach
      proved to be feasible to assess contractile function in all regions of the
      epididymal duct under near physiological conditions and provides a tool to
      evaluate acute (side) effects of drugs and to investigate various signaling
      pathways. 

PMID- 24662988
TI  - The risk of injury to the peroneal artery in the posterolateral approach to the
      distal tibia: a cadaver study.
AB  - OBJECTIVES: The posterolateral approach to the distal tibia allows excellent
      visualization, direct reduction, and stabilization of posterior malleolar
      fractures. Concomitant fractures of the lateral malleolus may be internally fixed
      through the same approach. The approach may also be used for pilon fractures and
      for bone grafting in nonunions. This study aims to establish the safe zone of
      proximal dissection to avoid injury to the peroneal vessels when performing the
      posterolateral approach to the distal tibia. METHODS: Twenty-six unpaired adult
      lower limbs were dissected using the posterolateral approach to the distal tibia.
      The peroneal artery was identified, as it coursed through the interosseous
      membrane on deep dissection and the level of its bifurcation was noted over the
      tibia. Perpendicular measurements were made from these points to the tibial
      plafond and distal fibula. RESULTS: The peroneal artery bifurcated at 83 +/- 21
      mm (range, 41-115 mm) proximal to the tibial plafond and 103 +/- 21 mm (range, 61
      136 mm) from the distal fibula. The peroneal artery perforated through the
      interosseous membrane 64 +/- 18 mm (range, 41-96 mm) proximal to the tibial
      plafond and 81 +/- 20 mm (range, 42-113 mm) from the distal fibula. CONCLUSIONS:
      The posterolateral approach to the distal tibia allows direct reduction of
      posterior malleolus fractures. The peroneal artery may bifurcate and perforate
      through the interosseous membrane as little as 41 mm from the tibial plafond.
      Dissection around this region should be performed with care due to the wide
      variation in vasculature, however, once the peroneal artery is mobilized, a
      buttress plate can easily be placed beneath it.

PMID- 24662989
TI  - Three-dimensional fluoroscopy-navigated percutaneous screw fixation of acetabular
      fractures.
AB  - OBJECTIVE: Anatomic reduction and articular restoration after acetabular
      fractures occur (Ac-Fxs) are accepted predictors for good function and slow
      progression of posttraumatic osteoarthritis of the hip. The aim of this study was
      to retrospectively analyze Ac-Fxs, which were treated with closed reduction and
      percutaneous (three-dimensional) fluoroscopy-based navigated screw fixation.
      DESIGN: Level 4, retrospective clinical and radiographic assessment. SETTING:
      Level 1 trauma center. PATIENTS: Twelve patients (male/female: 9/3; mean age: 60
      years; range: 16-80 years) with moderately displaced Ac-Fxs were included.
      INTERVENTION: In enrolled patients, the treatment involved percutaneous three
      dimensional fluoroscopy-based navigated lag screw positioning. Closed reduction
      was achieved by lag screws, or reduction was aided by the insertion of
      percutaneous Schanz pins. MAIN OUTCOME MEASUREMENTS: The quality of the reduction
      and screw positions were assessed using intraoperative and postoperative computed
      tomography scans. Functional outcome was assessed using the Harris hip score, the
      visual analog scale for pain, and the Tegener activity scale. RESULTS: A total of
      22 periacetabular screws were placed (mean: 1.8 +/- 1.1 screws/patient, range: 1
      5). The mean follow-up was done for 30 (16-72) months. The postoperative
      reduction was anatomical in all patients, and the mean fracture displacement was
      significantly reduced (gap: 4.1 +/- 1.8 mm to 0.4 +/- 0.7 mm/step: 1.4 +/- 0.6 mm
      to 0.2 +/- 0.4 mm). No secondary dislocations or malunions/nonunions were found.
      All screws correctly addressed the fracture morphology and corresponded to
      preoperative planning. The Harris hip score, the visual analog scale (motion),
      and Tegener activity scale showed excellent to very good results (92.4 +/- 6.8,
      1.9 +/- 1.3, and 3.8 +/- 1.6, respectively). CONCLUSIONS: The navigated,
      percutaneous screw fixation of selected Ac-Fxs is a promising method that allows
      for closed reduction and fixation while obtaining a very good radiographic and
      functional outcome. LEVEL OF EVIDENCE: Therapeutic level 4.

PMID- 24662990
TI  - Natural history of anterior chest wall numbness after plating of clavicle
      fractures: educating patients.
AB  - OBJECTIVES: Improved patient outcomes after plating of displaced clavicle
      fractures have been demonstrated by recent clinical studies. Many of these
      patients, however, complain of anterior chest wall numbness after this procedure;
      we hypothesize that numbness likely persists long term for many patients, but
      without effect on shoulder function. DESIGN: Prospective observational cohort.
      SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Adult patients undergoing
      plating of a displaced middle third diaphyseal clavicle fracture. INTERVENTION:
      Open reduction and internal fixation with superior clavicle plating. MAIN OUTCOME
      MEASUREMENTS: The primary outcome is anterior chest wall numbness size (in square
      centimeters) and location as measured with a numbness transparency grid.
      Secondary outcomes include Visual Analog scale, Disabilities of the Arm,
      Shoulder, and Hand, and Constant scores 1 year postoperatively. RESULTS: Twenty
      five of 27 consecutive patients met inclusion/exclusion criteria, with 92% 1-year
      follow-up. Numbness at 2 weeks is very common, involving 83% of patients, with a
      mean area of 44 cm. Numbness at 1 year remains relatively common, involving 52%
      of patients, with a mean area of 15 cm (66% decrease in area from 2 weeks, P =
      0.009). Numbness at 2 weeks predicted a 63% chance of continued 1-year numbness
      (37% resolved); Constant, Disabilities of the Arm, Shoulder, and Hand, and Visual
      Analog scale pain scores remained excellent in all patients at final follow-up,
      without correlation between numbness and outcome measures (r < 0.170).
      CONCLUSIONS: Anterior chest wall numbness after open reduction internal fixation
      of displaced clavicle fractures is very common in the early postoperative period
      and may remain high 1 year postoperatively. Numbness 1 year after surgery is not
      associated with poor clinical outcome measures. LEVEL OF EVIDENCE: Prognostic
      level IV. See instructions for authors for a complete description of levels of
      evidence.

PMID- 24662991
TI  - Modified osteotomy for symptomatic malunion of the humeral greater tuberosity.
AB  - Here, we describe a modified osteotomy for malunion of the greater tuberosity
      that facilitates bone union and prevents symptom recurrence. The 3 most important
      features of this technique are: (1) osteotomizing the displaced fragment that
      includes the bed of the fracture, (2) placing figure-of-eight sutures by passing
      suture threads from inside the medullary cavity through osseous holes made in the
      metaphysis, and (3) pushing the distal end of the osteotomized fragment into the
      medullary cavity and fixing it in place. This procedure was performed on 10
      patients who complained of clinical symptoms derived primarily from greater
      tuberosity malunion after fractures of various morphologies. Eight of these
      patients were available for follow-up examinations over 2 postoperative years.
      Constant score ratios comparing the repaired side to the uninjured side ranged
      from 82% to 100%. These results support the use of this modified osteotomy in
      achieving favorable bone union and in creating sufficient subacromial space to
      resolve most symptoms caused by these malunited proximal humeral fractures.

PMID- 24662992
TI  - Predictors of readmission in orthopaedic trauma surgery.
AB  - OBJECTIVES: This study of patients who had operative treatment of skeletal trauma
      addresses (1) the association between readmission within 30 days of discharge and
      comorbidities and (2) differences in factors associated with all-cause
      readmissions and those because of a surgical adverse event. DESIGN: Retrospective
      study. SETTING: Tertiary care referral center. PATIENTS: Three thousand four
      hundred fifty-two operations for skeletal trauma between 2008 and 2012 with
      comorbidities quantified using the updated Charlson comorbidity index (CCI).
      OUTCOME MEASUREMENT: Readmission to the hospital within 30 days of surgery and
      the subset of readmissions because of adverse events related directly to surgery.
      RESULTS: There was a significant association between readmission within 30 days
      of surgery and higher CCI (P < 0.001), older age (P < 0.001), and marital status
      (widowed) (P < 0.001). The factors associated with readmission related to an
      adverse event were identical. The best multivariable logistic regression models
      for all-cause 30-day readmission and 30-day readmission related to a surgical
      adverse event included CCI and older age in both models (odds ratio 1.1, P <
      0.01, pseudo R = 0.03). CONCLUSIONS: Older patients and patients with greater
      comorbidity are more likely to be readmitted within 30 days of surgery for
      musculoskeletal trauma, whether for a surgical adverse event or another reason.
      The best multivariable models predicted very little of the variability in
      readmission, which reflects the complexity of readmission and the difficulty
      reducing the risk to a few specific factors. LEVEL OF EVIDENCE: Prognostic Level
      II. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24662993
TI  - Substantial improvement in prophylactic antibiotic administration for open
      fracture patients: results of a performance improvement program.
AB  - OBJECTIVES: Administration of early and appropriate antibiotic in treating
      patients with open fractures is an important early factor in preventing infection
      and optimizing outcomes. The purpose of this study is to evaluate the effects of
      an orthopaedic trauma performance improvement program directed at early
      antibiotic administration for open fracture patients at our trauma center.
      DESIGN: Retrospective comparative cohort study of patients treated for an open
      fracture by before and after implementation of our performance improvement
      program specifically designed to address early open fracture care. SETTING:
      Single metropolitan level 2 regional trauma center. PATIENTS: Patients with open
      fractures treated by orthopaedic surgery (hand and spine excluded) at our
      institution between January 2012 and December 2013 were included. Patients
      transferred from another facility were excluded. INTERVENTION: Patients were
      divided into one of the following 2 groups. Group 1 included patients treated
      before our open fracture performance improvement program (January 2012-December
      2012) and group 2 comprised those treated after the program was instituted
      (January 2013-December 2013). MAIN OUTCOME MEASUREMENTS: Patient demographics,
      injury factors, and performance measures relating to early open fracture care
      [eg, the characteristics of early antibiotic administration in their treatment
      course, including timeliness of prophylactic intravenous (IV) antibiotic therapy
      and reasons for delay or omission of these treatments] were evaluated. RESULTS:
      Group 1 was comprised of 127 patients with a total of 142 open fractures, whereas
      group 2 included 132 patients with a total of 156 open fractures. Patient and
      injury factors were not significantly different between the 2 groups. Group 1
      received IV antibiotics at an average of 70.5 minutes after arrival at our
      institution compared with group 2 who received antibiotics at an average of 32.4
      minutes (P < 0.001). The average times from emergency department arrival to
      physician evaluation improved from 6.5 to 4.5 minutes (P = 0.02) and antibiotic
      order to antibiotic delivery improved from 37 to 13 minutes (P < 0.001) for group
      1 compared with group 2, respectively. The average time between physician
      evaluation and antibiotic showed a trend toward improvement (12.7-8.0 minutes, P
      = 0.57). Fifty percent of patients in group 1 (63/127) had antibiotics initiated
      within 1 hour of hospital arrival, whereas 78% (100/132) in group 2 had
      antibiotics initiated within 1 hour (P < 0.001). Eighty-five percent (112/127) of
      patients in group 1 had antibiotics initiated within 3 hours of hospital arrival,
      whereas 95% (125/132) in group 2 had antibiotics initiated within 3 hours (P =
      0.03). Of those patients receiving standard antibiotics (cephalosporin), 79%
      (85/107) in group 1 and 91% (104/114) in group 2 received the recommended dose of
      IV antibiotic for their body weight (e.g., 2 g cefazolin for patients of >80 kg)
      (P < 0.006). CONCLUSIONS: Optimal treatment of open fracture patients with early
      and appropriate antibiotic prophylaxis was lacking for many patients at our
      trauma center. A multifaceted performance improvement program specifically
      concentrating on education, accountability, and antibiotic availability aimed at
      this aspect of orthopaedic trauma care was very effective in improving our early
      treatment of these patients. LEVEL OF EVIDENCE: Therapeutic level III. See
      instructions for authors for a complete description of levels of evidence.

PMID- 24662994
TI  - Effect of Calcar Screw Use in Surgical Neck Fractures of the Proximal Humerus
      With Unstable Medial Support: A Biomechanical Study.
AB  - OBJECTIVES: To evaluate the effect of calcar screw use in proximal humeral
      fractures with unstable medial support treated with locked plates. METHODS:
      Standard osteotomies were performed in 36 cadaveric humeri to create a surgical
      neck fracture proximal humeral model. For static testing, 12 pairs of humeri were
      divided into 4 groups: normal alignment and varus deformity groups with and
      without 5-mm medial deficiencies. Calcar screw function was measured in each
      group by axial, shear, and torsion stiffness tests. Another 6 pairs of humeri
      with 5-mm medial deficiencies were subjected to cyclic loading tests in the
      normal alignment model with and without calcar screw application. RESULTS: Calcar
      screws improved rotational stability in the normal alignment (P = 0.007) and
      varus (P = 0.002) groups. Calcar screws improved static and cyclic axial (P =
      0.004) and shear (P = 0.017) stability in the normal alignment group with medial
      deficiency. In specimens with normal alignment and intact medial cortex, calcar
      screws provided no advantage in axial (P = 0.535) or shear (P = 0.537) stiffness.
      Calcar screws did not provide sufficient axial (P = 0.782) or shear (P = 0.772)
      stability to avoid reduction loss in humeri with varus malreduction. CONCLUSIONS:
      In humeri with normal alignment, calcar screws can provide additional stability
      even when a medial deficiency exists. The use of calcar screws in humeri with
      varus deformity showed no biomechanical superiority.

PMID- 24662995
TI  - IL28B polymorphisms and clinical implications for hepatitis C virus infection in
      Uzbekistan.
AB  - AIMS: Genome-wide association studies highlighted single nucleotide polymorphisms
      (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients
      with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have
      population-specific correlation with spontaneous clearance of HCV. The aim of
      this study was to examine the prevalence and clinical significance of the
      outlined SNPs in a population from Central Asia, a multi-ethnic region with a
      developing economy and a high prevalence of HCV infection. METHODS: One hundred
      and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens
      were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs
      (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan
      assay, and by direct sequence analysis. The IFL4 region (ss469415590) was
      sequenced. RESULTS: Of the 135 patients that completed 24 or 48 weeks of
      treatment with Peg-IFN-alpha plus RBV, 87.4% were of Central Asian (CA) ancestry
      and 12.6% were of Eastern European (EE) ancestry. A non-virological response was
      observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860
      was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9-14.6;
      p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of
      outcome for CA group (OR, 6.9; 95% CI, 2.6-18.0; p<0.002). The allele frequency
      of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples.
      CONCLUSIONS: SNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome
      in a population of Central Asian ancestry.

PMID- 24662996
TI  - Clustering multivariate time series using Hidden Markov Models.
AB  - In this paper we describe an algorithm for clustering multivariate time series
      with variables taking both categorical and continuous values. Time series of this
      type are frequent in health care, where they represent the health trajectories of
      individuals. The problem is challenging because categorical variables make it
      difficult to define a meaningful distance between trajectories. We propose an
      approach based on Hidden Markov Models (HMMs), where we first map each trajectory
      into an HMM, then define a suitable distance between HMMs and finally proceed to
      cluster the HMMs with a method based on a distance matrix. We test our approach
      on a simulated, but realistic, data set of 1,255 trajectories of individuals of
      age 45 and over, on a synthetic validation set with known clustering structure,
      and on a smaller set of 268 trajectories extracted from the longitudinal Health
      and Retirement Survey. The proposed method can be implemented quite simply using
      standard packages in R and Matlab and may be a good candidate for solving the
      difficult problem of clustering multivariate time series with categorical
      variables using tools that do not require advanced statistic knowledge, and
      therefore are accessible to a wide range of researchers. 

PMID- 24662997
TI  - Utilization of Norway's emergency wards: the second 5 years after the
      introduction of the patient list system.
AB  - Utilization of services is an important indicator for estimating access to
      healthcare. In Norway, the General Practitioner Scheme, a patient list system,
      was established in 2001 to enable a stable doctor-patient relationship. Although
      satisfaction with the system is generally high, people often choose a more
      accessible but inferior solution for routine care: emergency wards. The aim of
      the article is to investigate contact patterns in primary health care situations
      for the total population in urban and remote areas of Norway and for major
      immigrant groups in Oslo. The primary regression model had a cross-sectional
      study design analyzing 2,609,107 consultations in representative municipalities
      across Norway, estimating the probability of choosing the emergency ward in
      substitution to a general practitioner. In a second regression model comprising
      625,590 consultations in Oslo, we calculated this likelihood for immigrants from
      the 14 largest groups. We noted substantial differences in emergency ward
      utilization between ethnic Norwegians both in rural and remote areas and among
      the various immigrant groups residing in Oslo. Oslo utilization of emergency ward
      services for the whole population declined, and so did this use among all
      immigrant groups after 2009. Other municipalities, while overwhelmingly
      ethnically Norwegian, showed diverse patterns including an increase in some and a
      decrease in others, results which we were unable to explain. 

PMID- 24662998
TI  - Socioeconomic inequalities in adult obesity prevalence in South Africa: a
      decomposition analysis.
AB  - In recent years, there has been a dramatic increase in obesity in low and middle
      income countries. However, there is limited research in these countries showing
      the prevalence and determinants of obesity. In this study, we examine the
      socioeconomic inequalities in obesity among South African adults. We use
      nationally representative data from the South Africa National Income Dynamic
      Survey of 2008 to: (1) construct an asset index using multiple correspondence
      analyses (MCA) as a proxy for socioeconomic status; (2) estimate concentration
      indices (CI) to measure socioeconomic inequalities in obesity; and (3) perform a
      decomposition analysis to determine the factors that contribute to socioeconomic
      related inequalities. Consistent with other studies, we find that women are more
      obese than men. The findings show that obesity inequalities exist in South
      Africa. Rich men are more likely to be obese than their poorer counterparts with
      a concentration index of 0.27. Women on the other hand have similar obesity
      patterns, regardless of socioeconomic status with CI of 0.07. The results of the
      decomposition analysis suggest that asset index contributes positively and highly
      to socio-economic inequality in obesity among females; physical exercise
      contributes negatively to the socio-economic inequality. In the case of males,
      educational attainment and asset index contributed more to socio-economic
      inequalities in obesity. Our findings suggest that focusing on economically well
      off men and all women across socioeconomic status is one way to address the
      obesity problem in South Africa. 

PMID- 24662999
TI  - Identification of health risks of hand, foot and mouth disease in China using the
      geographical detector technique.
AB  - Hand, foot and mouth disease (HFMD) is a common infectious disease, causing
      thousands of deaths among children in China over the past two decades.
      Environmental risk factors such as meteorological factors, population factors and
      economic factors may affect the incidence of HFMD. In the current paper, we used
      a novel model-geographical detector technique to analyze the effect of these
      factors on the incidence of HFMD in China. We collected HFMD cases from 2,309
      counties during May 2008 in China. The monthly cumulative incidence of HFMD was
      calculated for children aged 0-9 years. Potential risk factors included
      meteorological factors, economic factors, and population density factors. Four
      geographical detectors (risk detector, factor detector, ecological detector, and
      interaction detector) were used to analyze the effects of some potential risk
      factors on the incidence of HFMD in China. We found that tertiary industry and
      children exert more influence than first industry and middle school students on
      the incidence of HFMD. The interactive effect of any two risk factors increases
      the hazard for HFMD transmission. 

PMID- 24663000
TI  - Comparison of ambulatory versus video urodynamics in patients with spinal cord
      injury.
AB  - OBJECTIVE: To compare the data obtained through video urodynamics (VUD) with
      those obtained through one voiding cycle ambulatory urodynamics monitoring (AUM)
      in patients with spinal cord injury (SCI). METHODS: A comparative study was
      conducted in 69 patients with SCI (mean age+/-s.d. 44+/-16.9 years), 51 men and
      18 women, who were subjected to AUM and VUD. RESULTS: A lack of agreement was
      observed between the two tests with respect to the cystometric capacity (CC) (ml)
      (275+/-197.2 AUM versus 416+/-198.3 VUD), filling pressure (cm H2O) (4+/-5.3 AUM
      versus 9+/-12.5 VUD), bladder compliance (ml cm(-1) H2O) (116+/-114.9 AUM versus
      161+/-179.4 VUD), maximum detrusor contraction pressure (cm H2O) (87+/-65.2 AUM
      versus 47+/-35.0 VUD), post-void residual (ml) (206+/-201.5 AUM versus 308+/
      237.7 VUD) and stress urinary incontinence (kappa index: -0.052). Only the CC
      obtained in the AUM was in agreement with the mean bladder volume gathered from
      the frequency-volume chart. Agreement was observed with respect to the presence
      of neurogenic detrusor overactivity (kappa index: 0.307) and bladder outlet
      obstruction index (cm H2O) (17+/-48.0 AUM versus 15+/-18.7 VUD). There was no
      clear association between AUM parameters and bladder neck morphology, the
      presence of radiological detrusor-external sphincter dyssynergy or vesicoureteral
      reflux observed in the VUD. CONCLUSION: The differences between both methods
      discourage the use of AUM with just one voiding cycle in the evaluation of
      patients with SCI.

PMID- 24663001
TI  - Sympathetic single axonal discharge after spinal cord injury in humans: activity
      at rest and after bladder stimulation.
AB  - STUDY DESIGN: Clinical experimental mechanistic study. OBJECTIVES: (1) To
      determine in three spinal cord-injured patients whether individual muscle
      sympathetic nerve fibres below the level of the spinal lesion display spontaneous
      activity. (2) To determine in these patients if individual sympathetic
      vasoconstrictor fibres show a prolonged discharge following a bladder stimulus.
      SETTING: University hospital in Gothenburg, Sweden. METHODS: Microneurographic
      recordings of action potentials from individual muscle nerve sympathetic fibres
      in a peroneal nerve. Recordings of skin blood flow and electrodermal responses in
      a foot. RESULTS: In all patients, there was sparse ongoing spontaneous impulse
      traffic in individual sympathetic fibres. Brisk mechanical pressure over the
      urinary bladder evoked a varying number of action potentials in individual
      fibres, but the activity was brief and did not continue after the end of the
      evoked multiunit burst. CONCLUSION: Prolonged discharges in individual
      sympathetic fibres are unlikely to contribute to a long duration of blood
      pressure increases induced by brief bladder stimuli.

PMID- 24663002
TI  - Longitudinal employment outcomes in adults with pediatric-onset spinal cord
      injury.
AB  - STUDY DESIGN: Longitudinal survey. OBJECTIVES: To determine in adults with
      pediatric-onset spinal cord injury (SCI) employment outcomes, longitudinal
      changes in employment over time and changes in psychosocial outcomes associated
      with employment status. SETTING: Community setting. METHODS: Adults who had
      sustained a SCI before 19 years of age and had completed at least three
      consecutive annual interviews were included in the study. Generalized estimating
      equation models were formulated to obtain odds ratio (OR) of change in employment
      status and outcomes over time. RESULTS: Total 1691 interviews were conducted in
      283 participants, 182 men and 101 women (88% Caucasian; age at baseline, 27.3+/
      3.7 years; duration at baseline, 12.7+/-5.0 years). At the last interview (age,
      34.4+/-5.2 years; duration, 19.9+/-6.1 years), 49.5% were employed and 47.0% had
      a baccalaureate or post-baccalaureate degree. There was no significant change in
      employment status over time (OR 1.01, confidence interval (CI) 0.98-1.04). Odds
      of employment increased over time in participants who were women (1.04, CI 1.00
      1.08), married (1.05, CI 1.02-1.08) and attained baccalaureate (1.03, CI 1.00
      1.07) or post-baccalaureate (1.05, CI 1.02-1.08) degree. Employment odds
      decreased with occurrence of autonomic dysreflexia (0.80, CI 0.65-0.99),
      spasticity (0.80, CI 0.59-0.99) or chronic medical condition (0.83, CI 0.71
      0.98). Life satisfaction scores increased over time in those who remained
      employed (1.11, CI 1.01-1.22); odds of depression increased over time in those
      who remained unemployed (1.13, CI 1.04-1.23). CONCLUSION: Employment status
      remained relatively stable in adults with pediatric-onset SCI; however, changes
      in employment were associated with education, secondary health conditions and
      psychosocial well-being.

PMID- 24663003
TI  - Rehabilitation outcomes following infections causing spinal cord myelopathy.
AB  - STUDY DESIGN: Retrospective, open-cohort, consecutive case series. OBJECTIVE: To
      describe the demographic characteristics, clinical features and outcomes in
      patients undergoing initial in-patient rehabilitation after an infectious cause
      of spinal cord myelopathy. SETTING: Spinal Rehabilitation Unit, Melbourne,
      Victoria, Australia. Admissions between 1 January 1995 and 31 December 2010.
      METHODS: The following data were recorded: aetiology of spinal cord infection,
      risk factors, rehabilitation length of stay (LOS), level of injury (paraplegia vs
      tetraplegia), complications related to spinal cord damage and discharge
      destination. The American Spinal Injury Association (ASIA) Impairment Scale (AIS)
      and functional independence measure (FIM) were assessed at admission and at
      discharge. RESULTS: Fifty-one patients were admitted (men=32, 62.7%) with a
      median age of 65 years (interquartile range (IQR) 52-72, range 22-89). On
      admission, 37 (73%) had paraplegic level of injury and most patients (n=46, 90%)
      had an incomplete grade of spinal damage. Infections were most commonly bacterial
      (n=47, 92%); the other causes were viral (n=3, 6%) and tuberculosis (n=1, 2%).
      The median LOS was 106 days (IQR 65-135). The most common complications were pain
      (n=47, 92%), urinary tract infection (n=27, 53%), spasticity (n=25, 49%) and
      pressure ulcer during acute hospital admission (n=19, 37%). By the time of
      discharge from rehabilitation, patients typically showed a significant change in
      their AIS grade of spinal damage (P<0.001). They also showed significant
      improvement (P<0.001) in their FIM motor score (at admission: median=27, IQR 20
      34; at discharge: median=66, IQR 41-75). CONCLUSION: Most patients returned home
      with a good level of functioning with respect to mobility, bladder and bowel
      status, and their disability improved significantly.

PMID- 24663004
TI  - Thermoregulatory responses in wheelchair tennis players: a pilot study.
AB  - STUDY DESIGN: This was an observational study. OBJECTIVES: Spinal cord-injured
      (SCI) individuals are thermoregulatory compromised because of an inability to
      vasodilate and sweat below the injury, increasing the risk, proportional to the
      injury level, for marked core body temperature (CBT) rises. We compared
      thermoregulatory responses between wheelchair tennis players with and without a
      SCI. SETTING: British Open 2013, Nottingham, UK. METHODS: A total of 8 (3 SCI and
      5 non-SCI) wheelchair tennis players played a 45-min match while we continuously
      measured CBT, 8-point skin temperature (Mean-Tsk) and exercise intensity
      (metabolic equivalent units (METs)). Thermal sensation and perceived exertion
      were measured before and after each set. Video-assisted logging of each serve,
      stroke and point duration was used to determine match intensity. No statistics
      were performed for CBT because of small sample sizes. RESULTS: Wet Bulb Globe
      Temperature varied between 18 and 20  degrees C. CBT increased stronger in the
      SCI players (+0.6+/-0.1  degrees C; n=2) compared with the non-SCI players
      (+0.3+/-0.1  degrees C; n=4), whereas Mean-Tsk was similar between groups
      (P=0.29). No Tsk differences were observed above (>T6) or below (< or =T6) the
      lesion level. Thermal sensation, perceived exertion, exercise and match intensity
      were similar between groups (all P>0.05). CONCLUSIONS: In this small, descriptive
      study, CBT increased slightly more in the SCI wheelchair tennis players compared
      with non-SCI players during a 45-min match in moderate environmental conditions.
      Further research to investigate whether SCI players are more prone to heat
      illness is warranted.

PMID- 24663005
TI  - Do American goldfinches see their world like passive prey foragers? A study on
      visual fields, retinal topography, and sensitivity of photoreceptors.
AB  - Several species of the most diverse avian order, Passeriformes, specialize in
      foraging on passive prey, although relatively little is known about their visual
      systems. We tested whether some components of the visual system of the American
      goldfinch (Spinus tristis), a granivorous bird, followed the profile of species
      seeking passive food items (small eye size relative to body mass, narrow
      binocular fields and blind areas, centrally located retinal specialization
      projecting laterally, ultraviolet-sensitive vision). We measured eye size, visual
      field configuration, the degree of eye movement, variations in the density of
      ganglion cells and cone photoreceptors, and the sensitivity of photoreceptor
      visual pigments and oil droplets. Goldfinches had relatively large binocular (46
      degrees ) and lateral (134 degrees ) visual fields with a high degree of eye
      movement (66 degrees  at the plane of the bill). They had a single
      centrotemporally located fovea that projects laterally, but can be moved closer
      to the edge of the binocular field by converging the eyes. Goldfinches could also
      increase their panoramic vision by diverging their eyes while handling food items
      in head-up positions. The distribution of photoreceptors indicated that the
      highest density of single and double cones was surrounding the fovea, making it
      the center of chromatic and achromatic vision and motion detection. Goldfinches
      possessed a tetrachromatic ultraviolet visual system with visual pigment peak
      sensitivities of 399 nm (ultraviolet-sensitive cone), 442 nm (short-wavelength
      sensitive cone), 512 nm (medium-wavelength-sensitive cone), and 580 nm (long
      wavelength-sensitive cone). Overall, the visual system of American goldfinches
      showed characteristics of passive as well as active prey foragers, with a single
      fovea configuration and a large degree of eye movement that would enhance food
      searching and handling with their relatively wide binocular fields.

PMID- 24663007
TI  - Dentoskeletal effects of Twin Block and Herbst appliances in patients with Class
      II division 1 mandibular retrognathy.
AB  - OBJECTIVE: The aim of this study is to evaluate dentoskeletal effects of Herbst
      and Twin Block (TB) appliance therapies in Skeletal Class II malocclusion.
      SUBJECTS AND METHODS: Herbst group consisted of 11 girls and 9 boys (mean age =
      12.74 +/- 1.43 years), TB group comprised of 10 girls and 10 boys (mean age =
      13.0 +/- 1.32 years), and control group included 9 girls and 11 boys (mean age =
      12.17 +/- 1.47 years). Mean treatment/observation times were 15.81 +/- 5.96
      months for Herbst, 16.20 +/- 7.54 months for TB, and 15.58 +/- 3.13 months for
      control group. Pre-treatment (T0) and post-treatment (T1) lateral cephalograms
      were traced using a modified Pancherz's cephalometric analysis. Inter-group
      differences were evaluated with one-way analysis of variance, and intra-group
      differences were assessed with paired samples t-test at the P < 0.05 level.
      RESULTS: In control group, all sagittal and vertical skeletal measurements
      increased as a result of continuing growth. However, skeletal discrepancy and
      overjet remained unchanged. After functional appliance therapy, greater increases
      were recorded in TB group for all mandibular skeletal measurements compared with
      those in control group. Upper dental arch distalization and lower incisor
      protrusion were significant in Herbst group, compared with control. All face
      height measurements increased after functional appliance therapy. IMPLICATIONS
      AND CONCLUSIONS: In TB group, the treatment effects were mainly due to mandibular
      skeletal changes. Both skeletal and dental changes contribute to Class II
      correction with Herbst appliance therapy. Herbst appliance may be especially
      useful in Skeletal Class II patients with maxillary dentoalveolar protrusion and
      mandibular dentoalveolar retrusion, whereas TB appliance may be preferred for
      skeletal mandibular retrognathy patients.

PMID- 24663006
TI  - Neural correlates of impaired vision in adolescents born extremely preterm and/or
      extremely low birthweight.
AB  - BACKGROUND: Adolescents born extremely preterm (EP; <28 weeks' gestation) and/or
      extremely low birthweight (ELBW; <1000 g) experience high rates of visual
      impairments, however the potential neural correlates of visual impairments in
      EP/ELBW adolescents require further investigation. This study aimed to: 1)
      compare optic radiation and primary visual cortical structure between EP/ELBW
      adolescents and normal birthweight controls; 2) investigate associations between
      perinatal factors and optic radiation and primary visual cortical structure in
      EP/ELBW adolescents; 3) investigate associations between optic radiation and
      primary visual cortical structure in EP/ELBW adolescents and the odds of impaired
      vision. METHODS: 196 EP/ELBW adolescents and 143 controls underwent magnetic
      resonance imaging at a mean age of 18 years. Optic radiations were delineated
      using constrained spherical deconvolution based probabilistic tractography.
      Primary visual cortices were segmented using FreeSurfer software. Diffusion
      tensor variables and tract volume of the optic radiations, as well as volume,
      surface area and thickness of the primary visual cortices, were estimated.
      RESULTS: Axial, radial and mean diffusivities within the optic radiations, and
      primary visual cortical thickness, were higher in the EP/ELBW adolescents than
      controls. Within EP/ELBW adolescents, postnatal corticosteroid exposure was
      associated with altered optic radiation diffusion values and lower tract volume,
      while decreasing gestational age at birth was associated with increased primary
      visual cortical volume, area and thickness. Furthermore, decreasing optic
      radiation fractional anisotropy and tract volume, and increasing optic radiation
      diffusivity in EP/ELBW adolescents were associated with increased odds of
      impaired vision, whereas primary visual cortical measures were not associated
      with the odds of impaired vision. CONCLUSIONS: Optic radiation and primary visual
      cortical structure are altered in EP/ELBW adolescents compared with controls,
      with the greatest alterations seen in those exposed to postnatal corticosteroids
      and those born earliest. Structural alterations to the optic radiations may
      increase the risk of impaired vision in EP/ELBW adolescents.

PMID- 24663008
TI  - Perception of laypersons and dental professionals and students as regards the
      aesthetic impact of gingival plastic surgery.
AB  - OBJECTIVE: To evaluate the degree of perception of laypersons, professionals, and
      dental students, regarding the aesthetic appearance of the smile in cases of
      gingival plastic surgery of the maxilla for correction of a gingival smile, by
      examining alterations in photographs. MATERIALS/METHODS: Alterations were made to
      an extraoral front-view-photograph of a gingival smile in normal occlusion, by
      gingival recontouring of the maxilla, simulating a gingival plastic surgery
      procedure to diminish gingival exposure. For this purpose, specific image
      manipulation program (Adobe-Photoshop-Software-CS3) was used. Images were printed
      on photographic-paper, attached to questionnaire, distributed among laypersons,
      professionals, and dental students to evaluate degree of aesthetics (n = 150). To
      evaluate degree of aesthetics, an attractiveness scale was used, with 0
      representing hardly attractive, 5 for attractive, and 10 for very attractive.
      Differences between examiners were examined by Mann-Whitney test. All the
      statistics were performed with a confidence level of 95 per cent. RESULTS: Both
      dental professionals and students and laypersons were capable of identifying
      alterations resulting from gingival plastic surgery. In all evaluated groups,
      they demonstrated that large gingival extension does not always affect aesthetic
      appearance of the smile, and maxillary incisors not being much visualized is
      characterized as hardly attractive, with statistically lower scores being
      attributed (P < 0.05). CONCLUSIONS: According to aesthetic parameters, the
      presence of the gingiva is important in the composition of the smile, however,
      only when exposed to small extent.

PMID- 24663010
TI  - Hippocampal HDAC4 contributes to postnatal fluoxetine-evoked depression-like
      behavior.
AB  - Fluoxetine treatment in adulthood evokes antidepressant and anxiolytic responses.
      Paradoxically, postnatal fluoxetine (PNFlx) induces persistent depression- and
      anxiety-like behaviors. The mechanistic underpinnings of this paradox remain
      poorly understood. Here, we examined specific molecular changes in the rat
      hippocampus that accompany perturbed emotionality observed across life following
      PNFlx. PNFlx-induced hippocampal gene regulation observed in microarray and
      quantitative PCR studies indicate functional enrichment of genes involved in
      response to organic substances, protein kinase pathways, DNA binding, and
      transcriptional repression. We noted specific transcripts (Hdac4, mammalian
      target of rapamycin (mTOR), Gnai1, protein kinase C gamma (Prkcc), and
      hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1)) that were
      consistently dysregulated across life, and selectively influenced by postnatal,
      but not adult, fluoxetine. Increased histone deacetylase-4 (HDAC4) recruitment,
      accompanied by decreased activating histone acetylation marks at the mTOR and
      Gnai1 promoters, indicate a role for HDAC4 in PNFlx-mediated gene dysregulation.
      Strikingly, coadministration of the HDAC inhibitor sodium butyrate with PNFlx
      prevented the dysregulation of Hdac4 and mTOR, and the emergence of depression-
      and anxiety-like behavior. Importantly, we also find that retreatment of PNFlx
      animals with fluoxetine in adulthood reversed the increased Hdac4 expression,
      prevented HDAC4 recruitment to the mTOR and Gnai1 promoters, and attenuated the
      decline in mTOR and Gnai1 expression, coincident with normalization of PNFlx
      evoked depression- and anxiety-like behavior. Further, we show that viral
      mediated hippocampal overexpression of Hdac4 was sufficient to induce depression
      , but not anxiety-, like behavior in adulthood. Our results highlight the unique
      nature of molecular signatures evoked by PNFlx, and implicate HDAC4 in the
      dysregulated gene expression and emergence of perturbed emotionality following
      fluoxetine exposure in early life. 

PMID- 24663012
TI  - Laryngoscopic, acoustic, perceptual, and functional assessment of voice in rock
      singers.
AB  - OBJECTIVE: The present study aimed to vocally assess a group of rock singers who
      use growl voice and reinforced falsetto. METHOD: A group of 21 rock singers and a
      control group of 18 pop singers were included. Singing and speaking voice was
      assessed through acoustic, perceptual, functional and laryngoscopic analysis.
      RESULTS: No significant differences were observed between groups in most of the
      analyses. Acoustic and perceptual analysis of the experimental group demonstrated
      normality of speaking voice. Endoscopic evaluation showed that most rock singers
      presented during singing voice a high vertical laryngeal position, pharyngeal
      compression and laryngeal supraglottic compression. Supraglottic activity during
      speaking voice tasks was also observed. However, overall vocal fold integrity was
      demonstrated in most of the participants. Slightly abnormal observations were
      demonstrated in few of them. Singing voice handicap index revealed that the most
      affected variable was the physical sphere, followed by the social and emotional
      spheres. CONCLUSIONS: Although growl voice and reinforced falsetto represent
      laryngeal and pharyngeal hyperfunctional activity, they did not seem to
      contribute to the presence of any major vocal fold disorder in our subjects.
      Nevertheless, we cannot rule out the possibility that more evident vocal fold
      disorders could be found in singers who use these techniques more often and
      during a longer period of time.

PMID- 24663011
TI  - Glutamic acid decarboxylase 65: a link between GABAergic synaptic plasticity in
      the lateral amygdala and conditioned fear generalization.
AB  - An imbalance of the gamma-aminobutyric acid (GABA) system is considered a major
      neurobiological pathomechanism of anxiety, and the amygdala is a key brain region
      involved. Reduced GABA levels have been found in anxiety patients, and genetic
      variations of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA
      synthesis, have been associated with anxiety phenotypes in both humans and mice.
      These findings prompted us to hypothesize that a deficiency of GAD65, the GAD
      isoform controlling the availability of GABA as a transmitter, affects synaptic
      transmission and plasticity in the lateral amygdala (LA), and thereby interferes
      with fear responsiveness. Results indicate that genetically determined GAD65
      deficiency in mice is associated with (1) increased synaptic length and release
      at GABAergic connections, (2) impaired efficacy of GABAergic synaptic
      transmission and plasticity, and (3) reduced spillover of GABA to presynaptic
      GABAB receptors, resulting in a loss of the associative nature of long-term
      synaptic plasticity at cortical inputs to LA principal neurons. (4) In addition,
      training with high shock intensities in wild-type mice mimicked the phenotype of
      GAD65 deficiency at both the behavioral and synaptic level, indicated by
      generalization of conditioned fear and a loss of the associative nature of
      synaptic plasticity in the LA. In conclusion, GAD65 is required for efficient
      GABAergic synaptic transmission and plasticity, and for maintaining extracellular
      GABA at a level needed for associative plasticity at cortical inputs in the LA,
      which, if disturbed, results in an impairment of the cue specificity of
      conditioned fear responses typifying anxiety disorders. 

PMID- 24663013
TI  - Laboratory detection of artemisinin-resistant Plasmodium falciparum.
AB  - Conventional 48-h in vitro susceptibility tests have low sensitivity in
      identifying artemisinin-resistant Plasmodium falciparum, defined phenotypically
      by low in vivo parasite clearance rates. We hypothesized originally that this
      discrepancy was explained by a loss of ring-stage susceptibility and so developed
      a simple field-adapted 24-h trophozoite maturation inhibition (TMI) assay
      focusing on the ring stage and compared it to the standard 48-h schizont
      maturation inhibition (WHO) test. In Pailin, western Cambodia, where artemisinin
      resistant P. falciparum is prevalent, the TMI test mean (95% confidence interval)
      50% inhibitory concentration (IC50) for artesunate was 6.8 (5.2 to 8.3) ng/ml
      compared with 1.5 (1.2 to 1.8) ng/ml for the standard 48-h WHO test (P = 0.001).
      TMI IC50s correlated significantly with the in vivo responses to artesunate
      (parasite clearance time [r = 0.44, P = 0.001] and parasite clearance half-life
      [r = 0.46, P = 0.001]), whereas the standard 48-h test values did not. On
      continuous culture of two resistant isolates, the artemisinin-resistant phenotype
      was lost after 6 weeks (IC50s fell from 10 and 12 ng/ml to 2.7 and 3 ng/ml,
      respectively). Slow parasite clearance in falciparum malaria in western Cambodia
      results from reduced ring-stage susceptibility. 

PMID- 24663014
TI  - Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected
      patients receiving nevirapine- or efavirenz-based antiretroviral treatment.
AB  - This is a substudy of the Agence Nationale de Recherches sur le Sida et les
      Hepatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment
      of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the
      pharmacokinetics of rifampin or isoniazid with or without the coadministration of
      nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in
      HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on
      antituberculosis therapy based on rifampin and isoniazid participated in the
      substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median
      CD4(+) T cell count, 104 cells/MUl; median HIV-1 RNA load, 5.5 log copies/ml).
      The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight,
      respectively. Twenty-one patients received 200 mg of nevirapine twice a day
      (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in
      combination with lamivudine and stavudine from day 1 until the end of the study.
      Blood samples were collected at regular time-dosing intervals after morning
      administration of a fixed-dose combination of rifampin and isoniazid. When
      rifampin was administered alone, the median maximum concentration of drug in
      serum (Cmax) and the area under the concentration-time curve (AUC) at steady
      state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg . h/liter
      (range, 11.41 to 109.75 mg . h/liter), respectively. Concentrations remained
      unchanged when rifampin was coadministered with nevirapine or efavirenz. When
      isoniazid was administered alone, the median isoniazid Cmax and AUC at steady
      state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg . h/liter
      (range, 7.73 to 56.95 mg . h/liter), respectively. Concentrations remained
      unchanged when isoniazid was coadministered with nevirapine; however, a 29%
      decrease in the isoniazid AUC was observed when isoniazid was combined with
      efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when
      coadministered with nevirapine or efavirenz were not altered to a clinically
      significant extent in these severely immunosuppressed HIV-infected patients.
      Patients experienced favorable clinical outcomes. (This study has been registered
      at ClinicalTrials.gov under registration no. NCT00495326.). 

PMID- 24663016
TI  - Evaluation of ceftaroline, vancomycin, daptomycin, or ceftaroline plus daptomycin
      against daptomycin-nonsusceptible methicillin-resistant Staphylococcus aureus in
      an in vitro pharmacokinetic/pharmacodynamic model of simulated endocardial
      vegetations.
AB  - Infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus
      (MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate
      therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)
      nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are
      limited for IE. This study evaluated the activities of ceftaroline, vancomycin,
      daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA
      in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial
      vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h)
      (maximum concentration of drug in serum [Cmax], 21.3 mg/liter; half-life [t1/2],
      2.66 h), daptomycin (10 mg/kg of body weight/day) (Cmax, 129.7 mg/liter; t1/2, 8
      h), vancomycin (1 g) q8h (minimum concentration of drug in serum [Cmin], 20
      mg/liter; t1/2, 5 h), and ceftaroline plus daptomycin were evaluated against 3
      clinical DNS, vancomycin-intermediate MRSA in a two-compartment, in vitro, PK/PD
      SEV model over 96 h with a starting inoculum of ~8 log10 CFU/g. Bactericidal
      activity was defined as a >= 3-log10 CFU/g reduction from the starting inoculum.
      Therapeutic enhancement of combinations was defined as >= 2-log10 CFU/g reduction
      over the most active agent alone. MIC values for daptomycin, vancomycin, and
      ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter,
      respectively, for all strains. At simulated exposures, vancomycin was
      bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h,
      ceftaroline monotherapy offered significantly improved killing compared to other
      agents against one strain. The combination of DAP plus CPT demonstrated
      therapeutic enhancement, resulting in significantly improved killing versus
      either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal
      activity against DNS, vancomycin-intermediate MRSA at high bacterial densities.
      Ceftaroline plus daptomycin may offer more rapid and sustained activity against
      some MRSA in the setting of high-inoculum infections like IE and should also be
      considered.

PMID- 24663015
TI  - Comparative study of the effects of antituberculosis drugs and antiretroviral
      drugs on cytochrome P450 3A4 and P-glycoprotein.
AB  - Predicting drug-drug interactions (DDIs) related to cytochrome P450 (CYP), such
      as CYP3A4 and one of the major drug transporters, P-glycoprotein (P-gp), is
      crucial in the development of future chemotherapeutic regimens to treat
      tuberculosis (TB) and TB/AIDS coinfection cases. We evaluated the effects of 30
      anti-TB drugs, novel candidates, macrolides, and representative antiretroviral
      drugs on human CYP3A4 activity using a commercially available screening kit for
      CYP3A4 inhibitors and a human hepatocyte, HepaRG. Moreover, in order to estimate
      the interactions of these drugs with human P-gp, screening for substrates was
      performed. For some substrates, P-gp inhibition tests were carried out using P-gp
      expressing MDCK cells. As a result, almost all the compounds showed the expected
      effects on human CYP3A4 both in the in vitro screening and in HepaRG cells.
      Importantly, the unproven mechanisms of DDIs caused by WHO group 5 drugs,
      thioamides, and p-aminosalicylic acid were elucidated. Intriguingly, clofazimine
      (CFZ) exhibited weak inductive effects on CYP3A4 at >0.25 MUM in HepaRG cells,
      while an inhibitory effect was observed at 1.69 MUM in the in vitro screening,
      suggesting that CFZ autoinduces CYP3A4 in the human liver. Our method, based on
      one of the pharmacokinetics parameters in humans, provides more practical
      information associated with not only DDIs but also with drug metabolism. 

PMID- 24663018
TI  - In vitro studies of Exserohilum rostratum with antifungal drugs and
      methylprednisolone.

PMID- 24663017
TI  - Simplified equations using two concentrations to calculate area under the curve
      for antimicrobials with concentration-dependent pharmacodynamics: daptomycin as a
      motivating example.
AB  - The effects of several antimicrobial agents are predicted by the ratio of the
      area under the concentration-time curve (AUC) to the MIC (AUC/MIC). Peak (Cp) and
      trough (Ct) concentrations are often measured clinically as surrogates of AUC
      because actual computation of AUC from 1 or 2 samples requires sophisticated
      mathematical methods. Given that the effects of daptomycin are predicted by
      AUC/MIC, our objective was to compare simple equation calculated AUC based on Cp
      and Ct to model integrated AUC. A standard population pharmacokinetic model was
      used to simulate 5,000 daptomycin concentration-time profiles after 5 doses of 6
      mg/kg of body weight/day (0.5-h infusions). The AUC for the 24-h period was
      computed by integration and by equations with 110 Cp-Ct combination pairs. The Cp
      time points were in 15-min increments between 0.5 h and 3 h and Ct in 15-min
      increments within an hour of the end of the dosing interval for each dose. The
      precision and bias of the calculated AUC relative to the integrated AUC were
      determined to identify Cp-Ct pairs associated with the lowest bias and highest
      precision. The equations were further validated using two daptomycin
      concentration-time data sets from healthy volunteers and critically ill patients.
      The precision and bias of calculated AUC were based primarily on Cp, and use of a
      daptomycin Cp 1.5 h to 3 h from the start of infusion was associated with a bias
      of <10% and an R(2) of >0.95. Data from the healthy volunteers and critically ill
      patients also demonstrated declining bias with use of Cp >= 1.5 h from the start
      of infusion with relatively good precision. Simplified equations using a
      daptomycin Cp approximately 2 h from the start of infusion and a Ct within an
      hour of the end of the dosing interval should yield precise and unbiased
      estimates of daptomycin AUC.

PMID- 24663019
TI  - Pharmacokinetics of cefuroxime in porcine cortical and cancellous bone determined
      by microdialysis.
AB  - Traditionally, the pharmacokinetics of antimicrobials in bone have been
      investigated using bone biopsy specimens, but this approach suffers from
      considerable methodological limitations. Consequently, new methods are needed.
      The objectives of this study were to assess the feasibility of microdialysis (MD)
      for measuring cefuroxime in bone and to obtain pharmacokinetic profiles for the
      same drug in porcine cortical and cancellous bone. The measurements were
      conducted in bone wax sealed and unsealed drill holes in cortical bone and in
      drill holes in cancellous bone and in subcutaneous tissue. As a reference, the
      free and total plasma concentrations were also measured. The animals received a
      bolus of 1,500 mg cefuroxime over 30 min. No significant differences were found
      between the key pharmacokinetic parameters for sealed and unsealed drill holes in
      cortical bone. The mean +/- standard error of the mean area under the
      concentration-time curve (AUC) values from 0 to 5 h were 6,013 +/- 1,339, 3,222
      +/- 1086, 2,232 +/- 635, and 952 +/- 290 min . MUg/ml for free plasma,
      subcutaneous tissue, cancellous bone, and cortical bone, respectively (P < 0.01,
      analysis of variance). The AUC for cortical bone was also significantly different
      from that for cancellous bone (P = 0.04). This heterogeneous tissue distribution
      was also reflected in other key pharmacokinetic parameters. This study validates
      MD as a suitable method for measuring cefuroxime in bone. Cefuroxime penetration
      was impaired for all tissues, and bone may not be considered one distinct
      compartment. 

PMID- 24663020
TI  - Novel functions of an iron-sulfur flavoprotein from Trichomonas vaginalis
      hydrogenosomes.
AB  - Iron-sulfur flavoproteins (Isf) are flavin mononucleotide (FMN)- and FeS cluster
      containing proteins commonly encountered in anaerobic prokaryotes. However, with
      the exception of Isf from Methanosarcina thermophila, which participates in
      oxidative stress management by removing oxygen and hydrogen peroxide, none of
      these proteins has been characterized in terms of function. Trichomonas
      vaginalis, a sexually transmitted eukaryotic parasite of humans, was found to
      express several iron-sulfur flavoprotein (TvIsf) homologs in its hydrogenosomes.
      We show here that in addition to having oxygen-reducing activity, the recombinant
      TvIsf also functions as a detoxifying reductase of metronidazole and
      chloramphenicol, both of which are antibiotics effective against a variety of
      anaerobic microbes. TvIsf can utilize both NADH and reduced ferredoxin as
      electron donors. Given the prevalence of Isf in anaerobic prokaryotes, we propose
      that these proteins are central to a novel defense mechanism against xenobiotics.

PMID- 24663022
TI  - In vitro and in vivo activities of three oxazolidinones against nonreplicating
      Mycobacterium tuberculosis.
AB  - Oxazolidinones represent a new class of antituberculosis drugs that exert their
      function by inhibiting protein synthesis. Here, we compared the activities of
      three oxazolidinones, linezolid, PNU-100480, and AZD5847, against latent
      tuberculosis using a simple model employing the streptomycin-starved
      Mycobacterium tuberculosis strain 18b. The in vitro drug susceptibility results
      showed that the three oxazolidinones had a bacteriostatic effect against actively
      growing bacilli but potent bactericidal activity against nonreplicating cells. In
      the murine model of latent infection with M. tuberculosis 18b, the efficacy of
      the three compounds varied greatly. Indeed, AZD5847 or its prodrug exhibited no
      activity or only modest activity, respectively, after 2 months of treatment,
      whereas both linezolid and PNU-100480 were effective against latent bacilli in
      mice and showed promising outcomes in combination therapy with rifampin.
      Moreover, the potency of PNU-100480 was significantly greater than that of
      linezolid, making it an attractive drug candidate in the development of new
      combination therapies for latent tuberculosis. 

PMID- 24663021
TI  - Lipopolysaccharide-binding alkylpolyamine DS-96 inhibits Chlamydia trachomatis
      infection by blocking attachment and entry.
AB  - Vaginally delivered microbicides are being developed to offer women self
      initiated protection against transmission of sexually transmitted infections such
      as Chlamydia trachomatis. A small molecule, DS-96, rationally designed for high
      affinity to Escherichia coli lipid A, was previously demonstrated to bind and
      neutralize lipopolysaccharide (LPS) from a wide variety of Gram-negative bacteria
      (D. Sil et al., Antimicrob. Agents Chemother. 51: 2811-2819, 2007,
      doi:10.1128/AAC.00200-07). Aside from the lack of the repeating O antigen,
      chlamydial lipooligosaccharide (LOS) shares general molecular architecture
      features with E. coli LPS. Importantly, the portion of lipid A where the
      interaction with DS-96 is expected to take place is well conserved between the
      two organisms, leading to the hypothesis that DS-96 inhibits Chlamydia infection
      by binding to LOS and compromising the function. In this study, antichlamydial
      activity of DS-96 was examined in cell culture. DS-96 inhibited the intercellular
      growth of Chlamydia in a dose-dependent manner and offered a high level of
      inhibition at a relatively low concentration (8 MUM). The data also revealed that
      infectious elementary bodies (EBs) were predominantly blocked at the attachment
      step, as indicated by the reduced number of EBs associated with the host cell
      surface following pretreatment. Of those EBs that were capable of attachment, the
      vast majority was unable to gain entry into the host cell. Inhibition of EB
      attachment and entry by DS-96 suggests that Chlamydia LOS is critical to these
      processes during the developmental cycle. Importantly, given the low association
      of host toxicity previously reported by Sil et al., DS-96 is expected to perform
      well in animal studies as an active antichlamydial compound in a vaginal
      microbicide. 

PMID- 24663023
TI  - Population pharmacokinetics and dosing optimization of vancomycin in children
      with malignant hematological disease.
AB  - An increase in vancomycin dose has been proposed in adults with malignant
      hematological disease. As pediatric data are limited, our aim was to evaluate the
      population pharmacokinetics of vancomycin in order to define the appropriate
      dosing regimen in children with malignant hematological disease. Vancomycin
      concentrations were collected prospectively during therapeutic monitoring.
      Population pharmacokinetic analysis was performed using NONMEM software. Seventy
      children (age range, 0.3 to 17.7 years) were included. With the current
      recommended dosing regimen of 40 to 60 mg/kg/day, 53 children (76%) had
      subtherapeutic steady-state trough concentrations (Css/min of <10 mg/liter). A
      one-compartment model with first-order elimination was developed. Systematic
      covariate analysis identified that weight significantly influenced clearance (CL)
      and volume of distribution (V) with power functions of 0.677 for CL and 0.838 for
      V. Vancomycin CL also significantly increased with increases in creatinine
      clearance and seemed to be higher in children with malignant hematological
      disease than in the general pediatric population. The model was validated
      internally. Its predictive performance was further confirmed in an external
      validation by Bayesian estimation. A patient-tailored dosing regimen was
      developed based on the final pharmacokinetic model and showed that a higher
      proportion of patients reached the target Css/min than with the traditional mg/kg
      basis dose (60% versus 49%) and that the risks associated with underdosing or
      overdosing were reduced. This is the first population pharmacokinetic study of
      vancomycin in children with malignant hematological disease. An optimized dosing
      regimen, taking into account patient weight, creatinine clearance, and
      susceptibility of the pathogens involved, could routinely be used to
      individualize vancomycin therapy in this vulnerable population. 

PMID- 24663024
TI  - Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase
      inhibitor.
AB  - BI 224436 is an HIV-1 integrase inhibitor with effective antiviral activity that
      acts through a mechanism that is distinct from that of integrase strand transfer
      inhibitors (INSTIs). This 3-quinolineacetic acid derivative series was identified
      using an enzymatic integrase long terminal repeat (LTR) DNA 3'-processing assay.
      A combination of medicinal chemistry, parallel synthesis, and structure-guided
      drug design led to the identification of BI 224436 as a candidate for preclinical
      profiling. It has antiviral 50% effective concentrations (EC50s) of <15 nM
      against different HIV-1 laboratory strains and cellular cytotoxicity of >90 MUM.
      BI 224436 also has a low, ~2.1-fold decrease in antiviral potency in the presence
      of 50% human serum and, by virtue of a steep dose-response curve slope, exhibits
      serum-shifted EC95 values ranging between 22 and 75 nM. Passage of virus in the
      presence of inhibitor selected for either A128T, A128N, or L102F primary
      resistance substitutions, all mapping to a conserved allosteric pocket on the
      catalytic core of integrase. BI 224436 also retains full antiviral activity
      against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H,
      and E92Q. In drug combination studies performed in cellular antiviral assays, BI
      224436 displays an additive effect in combination with most approved
      antiretrovirals, including INSTIs. BI 224436 has drug-like in vitro absorption,
      distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell
      permeability, solubility, and low cytochrome P450 inhibition. It exhibited
      excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic
      flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog
      (CL, 8%; F, 81%). Based on the excellent biological and pharmacokinetic profile,
      BI 224436 was advanced into phase 1 clinical trials. 

PMID- 24663025
TI  - Inhibitors of the tick-borne, hemorrhagic fever-associated flaviviruses.
AB  - No antiviral therapies are available for the tick-borne flaviviruses associated
      with hemorrhagic fevers: Kyasanur Forest disease virus (KFDV), both classical and
      the Alkhurma hemorrhagic fever virus (AHFV) subtype, and Omsk hemorrhagic fever
      virus (OHFV). We tested compounds reported to have antiviral activity against
      members of the Flaviviridae family for their ability to inhibit AHFV replication.
      6-Azauridine (6-azaU), 2'-C-methylcytidine (2'-CMC), and interferon alpha 2a (IFN
      alpha2a) inhibited the replication of AHFV and also KFDV, OHFV, and Powassan
      virus. The combination of IFN-alpha2a and 2'-CMC exerted an additive antiviral
      effect on AHFV, and the combination of IFN-alpha2a and 6-azaU was moderately
      synergistic. The combination of 2'-CMC and 6-azaU was complex, being strongly
      synergistic but with a moderate level of antagonism. The antiviral activity of 6
      azaU was reduced by the addition of cytidine but not guanosine, suggesting that
      it acted by inhibiting pyrimidine biosynthesis. To investigate the mechanism of
      action of 2'-CMC, AHFV variants with reduced susceptibility to 2'-CMC were
      selected. We used a replicon system to assess the substitutions present in the
      selected AHFV population. A double NS5 mutant, S603T/C666S, and a triple mutant,
      S603T/C666S/M644V, were more resistant to 2'-CMC than the wild-type replicon. The
      S603T/C666S mutant had a reduced level of replication which was increased when
      M644V was also present, although the replication of this triple mutant was still
      below that of the wild type. The S603 and C666 residues were predicted to lie in
      the active site of the AHFV NS5 polymerase, implicating the catalytic center of
      the enzyme as the binding site for 2'-CMC. 

PMID- 24663026
TI  - Maintenance of genetic diversity in an introduced island population of guanacos
      after seven decades and two severe demographic bottlenecks: implications for
      camelid conservation.
AB  - Fifteen guanacos were introduced to Staats Island in the Falklands/Malvinas
      archipelago from Patagonia in the 1930s. Twenty five years later, the population
      was culled from 300 to 10-20 individuals, but quickly rebounded to a population
      of almost 400 animals that today retain the genetic signature of the founding
      event and later bottleneck. The goals of this study were to (i) make a genetic
      assessment of this island population through comparisons with mainland
      populations and simulations, and (ii) assess the likely source-population of the
      introduced guanacos. Genetic variation was estimated from 513 bp of mitochondrial
      DNA sequence and 15 microsatellite loci among 154 guanacos collected from eight
      localities, including the adjacent mainland and the islands of Tierra del Fuego
      and Staats Island. Of the 23 haplotypes observed among our samples, the Staats
      Island population only contained three haplotypes, all of which were shared with
      the coastal Monte Leon population in southern Patagonia. Mitochondrial DNA and
      microsatellite variations on Staats Island were comparable to most mainland
      populations and greater than those observed on Tierra del Fuego. Patterns of
      genetic structure suggest that the Staats Island guanaco population was founded
      with animals from southern Patagonia (as opposed to northern Patagonia or Tierra
      del Fuego), but that effective reductions in population size lasted only a few
      generations and that surviving animals were a random sample of the pre-bottleneck
      genetic variation. 

PMID- 24663027
TI  - Emerging new anticancer biological therapies in 2013 (haematological
      malignancies).
AB  - PURPOSE OF REVIEW: Although some haematologic diseases such as Hodgkin lymphoma
      and aggressive lymphoma yield high response rates and acceptable overall survival
      in first-line treatment, relapse is still a challenge particularly in those
      patients not eligible for transplant. In acute leukaemias, the prognosis remains
      poor in general with standard chemotherapy, thus stressing the need for efficient
      alternate therapies. RECENT FINDINGS: In recent years, biological anticancer
      agents comprising mAbs, small targeted molecules or more recently bispecific T
      cell engaging molecules or chimeric antigen receptors have been developed in
      haematologic diseases. This review examines the recent advances in biotherapies
      in the fields of acute leukaemias, aggressive lymphoma, Hodgkin lymphoma and
      chronic lymphatic leukaemia. SUMMARY: Most biological anticancer agents are
      currently developed in the setting of relapsed or refractory disease. Some of
      them however are under development or are already used in first-line therapy
      wherein they have improved the prognosis of haematology patients.

PMID- 24663028
TI  - The single-channel regime of transport through random media.
AB  - The propagation of light through samples with random inhomogeneities can be
      described by way of transmission eigenchannels, which connect incoming and
      outgoing external propagating modes. Although the detailed structure of a
      disordered sample can generally not be fully specified, these transmission
      eigenchannels can nonetheless be successfully controlled and used for focusing
      and imaging light through random media. Here we demonstrate that in deeply
      localized quasi-1D systems, the single dominant transmission eigenchannel is
      formed by an individual Anderson-localized mode or by a 'necklace state'. In this
      single-channel regime, the disordered sample can be treated as an effective 1D
      system with a renormalized localization length, coupled through all the external
      modes to its surroundings. Using statistical criteria of the single-channel
      regime and pulsed excitations of the disordered samples allows us to identify
      long-lived localized modes and short-lived necklace states at long and short time
      delays, respectively. 

PMID- 24663029
TI  - Colonisation of the non-indigenous Pacific oyster crassostrea gigas determined by
      predation, size and initial settlement densities.
AB  - Survival of incipient non-indigenous populations is dramatically altered by early
      predation on new colonisers. These effects can be influenced by morphological
      traits, such as coloniser size and density. The Australian non-native Pacific
      Oyster Crassostrea gigas is generally more fecund and faster growing compared to
      the native Saccostrea glomerata found in the same habitat. It is therefore
      important to quantify how the two species differ in survival across coloniser
      density and predation gradients. This information could become pertinent to the
      management of wild and aquaculture populations of the non-native C. gigas. Using
      a field-based factorial experiment we model the survival of incipient populations
      of both the native S. glomerata and the non-indigenous C. gigas as a function of
      coloniser density, predator reduction and individual size. Unexpectedly, survival
      of the non-indigenous C. gigas increased compared to S. glomerata when
      individuals were larger. The proportional survival of newly colonised oyster
      populations also increased with larger initial populations, regardless of species
      identity. Further, predator reduction resulted in increased survival of both
      oyster species, irrespective of coloniser size or initial density. Here we
      quantitatively demonstrate the effects of recruit density and size on enhancing
      the survivability of incipient oyster populations. 

PMID- 24663030
TI  - Dapagliflozine (Farxiga) for type 2 diabetes.

PMID- 24663031
TI  - Macitentan (Opsumit) for pulmonary arterial hypertension.

PMID- 24663033
TI  - Potential role of IGF-1 z score to predict permanent linear growth impairment in
      children with IBD.
AB  - In this pilot study, we analyzed serum insulin-like growth factor 1 (IGF-1)- and
      IGF-binding protein-3-for-age z scores from 54 inflammatory bowel disease
      children with no, temporary, or permanent growth impairment. Although our
      findings did not reach statistical significance, patients with permanent linear
      growth impairment had lower IGF-1-for-age z scores (-1.76 [-2.25 to -0.43])
      compared with those with no or temporary growth impairment (-0.84 [-1.49 to 
      0.3]) and -1.16 [-1.59 to -1.51], respectively). IGF-binding protein-3 levels
      were similar across the 3 groups. In the absence of significant inflammation and
      malnutrition, lower IGF-1-for-age z scores may help distinguish patients likely
      to have permanent growth impairment from those whose growth impairment is likely
      to be temporary. 

PMID- 24663034
TI  - Do parents and children agree? Quality-of-life assessment of children with
      inflammatory bowel disease and their parents.
AB  - BACKGROUND AND OBJECTIVES: Multi-item measures of inflammatory bowel disease
      (IBD) activity based on clinical, laboratory, and/or endoscopic variables do not
      take into consideration the impact on the patients' emotional aspects and
      adaptation to the disease. The aim of the present study was to evaluate
      concordance between parent and child ratings of health-related quality of life on
      the IMPACT-III questionnaire in children with IBD. METHODS: The IMPACT-III
      questionnaire was used to measure quality of life in 27 patients (mean age 14.2
      +/- 3 years, 40% girls) and one of their parents (82% mothers). Most of the
      patients had inactive disease at the time of the study. Differences between
      parent-proxy ratings and child ratings on the IMPACT-III were compared via paired
      samples t tests, intraclass correlation coefficients, and standardized difference
      scores. RESULTS: Parent-proxy and patient ratings were similar on total IMPACT
      III and its related domains (bowel symptoms, systemic symptoms, social
      functioning, body image, treatment/interventions), except that significant
      differences on emotional functioning ratings were found (P = 0.003). Intraclass
      correlation coefficients showed medium-to-large effect sizes (range 0.52-0.88)
      and standardized difference scores showed varying degrees of bias depending on
      the domain measured (range -0.64 to 0.32). CONCLUSIONS: Parents served as a good
      proxy for quality-of-life ratings in this population of pediatric patients with
      IBD. The degree of concordance between parent and child scores, however, varied,
      as observed in the present study in which parents underreported their child's
      health-related quality of life on the IMPACT-III emotional functioning domain.

PMID- 24663036
TI  - Authors' response.

PMID- 24663035
TI  - European pediatricians' approach to children with GER symptoms: survey of the
      implementation of 2009 NASPGHAN-ESPGHAN guidelines.
AB  - OBJECTIVE: The aim of this study was to evaluate the current implementation of
      the 2009 North American Society for Pediatric Gastroenterology, Hepatology, and
      Nutrition-European Society for Pediatric Gastroenterology, Hepatology, and
      Nutrition guidelines, and to assess proton pump inhibitors' (PPIs) prescribing
      patterns among pediatricians from different European countries. METHODS: A
      randomly identified sample of general pediatricians distributed across 11
      European countries. They were asked to complete a case report-structured
      questionnaire investigating their approaches to infants, children, and
      adolescents with symptoms suggestive of gastroesophageal reflux. RESULTS: A total
      of 567 European general pediatricians completed the study questionnaire. Only
      1.8% of them showed complete adherence to the guidelines. Forty-six percent of
      them reported that they diagnose gastroesophageal reflux disease based on
      clinical symptoms irrespective of the age of the child; 39% prescribe PPIs in
      infants with unexplained crying and/or distressed behavior and 36% prescribe PPIs
      in infants with uncomplicated recurrent regurgitation and vomiting; 48%
      prescribed PPIs in children younger than 8 to 12 years with vomiting and
      heartburn, without specific testing; 45% discontinue PPI therapy abruptly rather
      than tapering the dose. The overall rate of pediatricians overprescribing PPIs
      was 82%. CONCLUSIONS: The overall results of our survey show that the majority of
      pediatricians are unaware of 2009 North American Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition-European Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition reflux guidelines and often prescribe
      PPIs despite a lack of efficacy for the symptoms being treated. The overdiagnosis
      of gastroesophageal reflux disease places undue burden on both families and
      national health systems, which has not been affected by the publication of
      international guidelines.

PMID- 24663038
TI  - Phylogeography of the tropical planktonic foraminifera lineage globigerinella
      reveals isolation inconsistent with passive dispersal by ocean currents.
AB  - Morphologically defined species of marine plankton often harbor a considerable
      level of cryptic diversity. Since many morphospecies show cosmopolitan
      distribution, an understanding of biogeographic and evolutionary processes at the
      level of genetic diversity requires global sampling. We use a database of 387
      single-specimen sequences of the SSU rDNA of the planktonic foraminifera
      Globigerinella as a model to assess the biogeographic and phylogenetic
      distributions of cryptic diversity in marine microplankton on a global scale. Our
      data confirm the existence of multiple, well isolated genetic lineages. An
      analysis of their abundance and distribution indicates that our sampling is
      likely to approximate the actual total diversity. Unexpectedly, we observe an
      uneven allocation of cryptic diversity among the phylogenetic lineages. We show
      that this pattern is neither an artifact of sampling intensity nor a function of
      lineage age. Instead, we argue that it reflects an ongoing speciation process in
      one of the three major lineages. Surprisingly, four of the six genetic types in
      the hyperdiverse lineage are biogeographically restricted to the Indopacific.
      Their mutual co-occurrence and their hierarchical phylogenetic structure provide
      no evidence for an origin through sudden habitat fragmentation and their
      limitation to the Indopacific challenges the view of a global gene flow within
      the warm-water provinces. This phenomenon shows that passive dispersal is not
      sufficient to describe the distribution of plankton diversity. Rather, these
      organisms show differentiated distribution patterns shaped by species
      interactions and reflecting phylogenetic contingency with unique histories of
      diversification rates. 

PMID- 24663037
TI  - Human urine-derived stem cells alone or genetically-modified with FGF2 Improve
      type 2 diabetic erectile dysfunction in a rat model.
AB  - AIM: The aim of this study was to determine the possibility of improving erectile
      dysfunction using cell therapy with either human urine-derived stem cells (USCs)
      or USCs genetically-modified with FGF2 in a type 2 diabetic rat model. METHODS:
      Human USCs were collected from 3 healthy donors. USCs were transfected with FGF2
      (USCs-FGF2). Sixty-five SD male rats were divided into five groups (G). A control
      group of normal rats (G1, n = 10), and four other test groups of type 2 diabetic
      erectile dysfunction rats: PBS as a negative control (G2, n = 10), USCs (G3, n =
      15), lentivirus-FGF2 (G4, n = 15), and USCs-FGF2 (G5, n = 15). Diabetes was
      induced in the rats via a high fat diet for 28 days and a subsequent
      intraperitoneal injection of streptozotocin (35 mg/kg). Erectile dysfunction was
      screened with apomorphine (100 MUg/kg). Cell injections in the test groups (G2
      G5) occurred directly into the corpora cavernosa. The implanted cells were
      tracked at 7 days (n = 5 animals/G) and 28 days (n = 10 animals/G) post
      injection. Mean arterial pressure (MAP), intracavernosal pressure (ICP),
      expression of endothelial markers (CD31, VEGF and eNOS), smooth muscle markers
      (desmin and smoothelin), histological changes and erectile function were assessed
      for each group. RESULTS: USCs expressed mesenchymal stem cell markers, and
      secreted a number of proangiogenic growth factors. USCs expressed endothelial
      cell markers (CD31 and vWF) after transfection with FGF2. Implanted USCs or USCs
      FGF2 displayed a significantly raised ICP and ICP/MAP ratio (p<0.01) 28 days
      after intracavernous injection. Although few cell were detected within the
      implanted sites, histological and western blot analysis demonstrated an increased
      expression of endothelial and smooth muscle markers within the cavernous tissue
      following USC or USC-FGF2 injection. CONCLUSIONS: The paracrine effect of USCs or
      USCs-FGF2 induced improvement of erectile function in type 2 diabetic rats by
      recruiting resident cells and increasing the endothelial expression and contents
      of smooth muscle.

PMID- 24663039
TI  - Quality control and evaluation of vaccines in China.
AB  - I was born in Luoyang in 1963, a city in China with thousands of years' history.
      The city is the eastern starting point of the Silk Road (BC 206-260 AD), a famous
      and long trade route in human history. Living in this ancient city, I grew up
      under the influence and impact of Chinese traditional culture. When I was a
      teenager, I once read a book "Yellow Emperor's Inner Canon" (Huang Di Nei Jing,
      written about 5th century BC), which is the oldest extant classic of traditional
      Chinese medicine. I was immediately attracted by an idea in it "prevention is
      better than cure," which is mean that the highest level of medical treatment is
      not to cure a disease, but to prevent the occurrence of diseases. I think even in
      the modern society, this is still the highest realm of medical treatment.
      Inspired by this view, I developed a strong interest in preventive medicine and
      majored in it during my college years. With an increasingly deeper understanding
      of preventive medicine, I gradually realized the importance of epidemiology and
      vaccinology in preventing infectious diseases. Fortunately, in 1991 I entered the
      group of professor Zhuang Hui in Peking University Health Science Center for a
      doctorate degree in epidemiology. Professor Zhuang who is an academician of the
      Chinese Academy of Engineering not only taught me how to do research, but showed
      me how to act like a scientist. I benefited greatly from his rigorous attitudes
      toward life and research. During this period, I focused on transmission routes of
      hepatitis C virus which made me increasingly recognized the great harm of
      hepatitis in China. It is well known that more than three-quarters of all liver
      cancer cases are thought to be attributable to hepatitis B or C. In China about
      110 000 people die from liver cancer each year, accounting 45% of the total
      number of deaths caused by liver cancer worldwide. 

PMID- 24663040
TI  - Association of co-occurring serious mental illness with emergency hospitalization
      in people with chronic kidney disease.
AB  - BACKGROUND/AIMS: Chronic kidney disease (CKD) and serious mental illness (SMI)
      are both associated with an increased risk for repeated hospitalization. The
      objective of this study was to determine if co-occurring SMI exacerbates the risk
      for subsequent hospitalization, particularly through the emergency department
      (ED), among people with CKD. METHODS: People hospitalized in Washington State
      from April 2006 to December 2008 were separated into cohorts with diagnoses of
      CKD (n = 31,166), SMI (defined by schizophrenia and/or mood disorder; n = 20,167)
      or CKD with co-occurring SMI (n = 717), and a reference cohort without either
      diagnosis (n = 548,532). Main outcomes were rehospitalization for condition(s)
      other than mental illness: (1) through the ED; (2) any admission, and (3)
      admission resulting in death. Cox regression was used to analyze time to main
      outcomes controlling for prespecified covariates associated with
      rehospitalization. RESULTS: The risk of rehospitalization via the ED was
      increased for people with CKD (hazard ratio, HR = 1.24, 95% confidence interval,
      CI = 1.21-1.28, p < 0.001) and co-occurring SMI (HR = 1.33, 95% CI = 1.29-1.38, p
      < 0.001) cohorts, but was significantly greater in the combined cohort (HR =
      1.55, 95% CI = 1.40-1.73, p < 0.001). Similarly, the risk of any
      rehospitalization was increased for CKD (HR = 1.21, 95% CI = 1.17-1.25, p <
      0.001) and co-occurring SMI (HR = 1.14, 95% CI = 1.11-1.17, p < 0.001) cohorts,
      while a significantly greater risk was observed for the combined cohort (HR =
      1.36, 95% CI = 1.24-1.48, p < 0.001). The risk of rehospitalization resulting in
      death was not significantly increased in the combined cohort. CONCLUSION: In
      people with CKD, co-occurring SMI increased the risk of experiencing
      rehospitalization, particularly through the ED. Studies of strategies to address
      SMI in the CKD population are needed to mitigate the risk of repeat hospital
      admissions.

PMID- 24663041
TI  - Long-term financial burden of breast cancer: experiences of a diverse cohort of
      survivors identified through population-based registries.
AB  - PURPOSE: To evaluate the financial experiences of a racially and ethnically
      diverse cohort of long-term breast cancer survivors (17% African American, 40%
      Latina) identified through population-based registries. METHODS: Longitudinal
      study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and
      reported to the SEER registries of metropolitan Los Angeles and Detroit. We
      surveyed 3,133 women approximately 9 months after diagnosis and 4 years later.
      Multivariable models evaluated correlates of self-reported decline in financial
      status attributed to breast cancer and of experiencing at least one type of
      privation (economically motivated treatment nonadherence and broader hardships
      related to medical expenses). RESULTS: Among 1,502 patients responding to both
      surveys, median out-of-pocket expenses were <= $2,000; 17% of respondents
      reported spending > $5,000; 12% reported having medical debt 4 years
      postdiagnosis. Debt varied significantly by race: 9% of whites, 15% of blacks,
      17% of English-speaking Latinas, and 10% of Spanish-speaking Latinas reported
      debt (P = .03). Overall, 25% of women experienced financial decline at least
      partly attributed to breast cancer; Spanish-speaking Latinas had significantly
      increased odds of this decline relative to whites (odds ratio [OR], 2.76; P =
      .006). At least one privation was experienced by 18% of the sample; blacks (OR,
      2.6; P < .001) and English-speaking Latinas (OR, 2.2; P = .02) were significantly
      more likely to have experienced privation than whites. CONCLUSION: Racial and
      ethnic minority patients appear most vulnerable to privations and financial
      decline attributable to breast cancer, even after adjustment for income,
      education, and employment. These findings should motivate efforts to control
      costs and ensure communication between patients and providers regarding financial
      distress, particularly for vulnerable subgroups.

PMID- 24663042
TI  - Rare case of syndrome of inappropriate antidiuretic hormone as the initial
      presentation of ovarian cancer recurrence.

PMID- 24663043
TI  - Osteopoikilosis: A Benign Condition With the Appearance of Metastatic Bone
      Disease.

PMID- 24663044
TI  - Physicians' attitudes about multiplex tumor genomic testing.
AB  - PURPOSE: Although predictive multiplex somatic genomic tests hold the potential
      to transform care by identifying targetable alterations in multiple cancer genes,
      little is known about how physicians will use such tests in practice.
      PARTICIPANTS AND METHODS: Before the initiation of enterprise-wide multiplex
      testing at a major cancer center, we surveyed all clinically active adult cancer
      physicians to assess their current use of somatic testing, their attitudes about
      multiplex testing, and their genomic confidence. RESULTS: A total of 160
      physicians participated (response rate, 61%): 57% were medical oncologists; 29%,
      surgeons; 14% radiation oncologists; 37%, women; and 83%, research principal
      investigators. Twenty-two percent of physicians reported low confidence in their
      genomic knowledge. Eighteen percent of physicians anticipated testing patients
      infrequently (<= 10%), whereas 25% anticipate testing most patients (>= 90%).
      Higher genomic confidence was associated with wanting to test a majority of
      patients (adjusted odds ratio [OR], 6.09; 95% CI, 2.1 to 17.5) and anticipating
      using actionable (adjusted OR, 2.46; 95% CI, 1.2 to 5.2) or potentially
      actionable (adjusted OR, 2.89; 95% CI, 1.1 to 7.9) test results to inform
      treatment recommendations. Forty-two percent of physicians endorsed disclosure of
      uncertain genomic findings to patients. CONCLUSION: Physicians at a tertiary-care
      National Cancer Institute-designated comprehensive cancer center varied
      considerably in how they planned to incorporate predictive multiplex somatic
      genomic tests into practice and in their attitudes about the disclosure of
      genomic information of uncertain significance. Given that many physicians
      reported low genomic confidence, evidence-based guidelines and enhanced physician
      genomic education efforts may be needed to ensure that genomically guided cancer
      care is adequately delivered.

PMID- 24663045
TI  - Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor
      buparlisib with letrozole in estrogen receptor-positive/human epidermal growth
      factor receptor 2-negative metastatic breast cancer.
AB  - PURPOSE: Buparlisib, an oral reversible inhibitor of all class I phosphoinositide
      3-kinases, has shown antitumoral activity against estrogen receptor (ER)-positive
      breast cancer cell lines and xenografts, alone and with endocrine therapy. This
      phase Ib study evaluated buparlisib plus letrozole's safety, tolerability, and
      preliminary activity in patients with metastatic ER-positive breast cancer
      refractory to endocrine therapy. PATIENTS AND METHODS: Patients received
      letrozole and buparlisib in two different administration schedules. Outcomes were
      assessed by standard solid-tumor phase I methods. [(18)F]fluorodeoxyglucose
      positron emission tomography/computed tomography ([(18)F]FDG-PET/CT) scans were
      done at baseline and 2 weeks after treatment initiation. Tumor blocks were
      collected for phosphoinositide-3-kinase pathway mutation analysis. RESULTS: Fifty
      one patients were allocated sequentially to continuous or intermittent (five
      on/two off days) buparlisib administration on an every-4-week schedule.
      Buparlisib's maximum-tolerated dose (MTD) was 100 mg/d. Common drug-related
      adverse events included <= grade 2 hyperglycemia, nausea, fatigue, transaminitis,
      and mood disorders. The clinical benefit rate (lack of progression >= 6 months)
      among all patients treated at the MTD was 31%, including two objective responses
      in the continuous dose arm. Of seven patients remaining on treatment >= 12
      months, three had tumors with PIK3CA hot-spot mutation. Patients exhibiting
      metabolic disease progression by [(18)F]FDG-PET/CT scan at 2 weeks progressed
      rapidly on therapy. CONCLUSION: The letrozole and buparlisib combination was
      safe, with reversible toxicities regardless of schedule administration. Clinical
      activity was observed independent of PIK3CA mutation status. No metabolic
      response by [(18)F]FDG-PET/CT scan at 2 weeks was associated with rapid disease
      progression. Phase III trials of buparlisib and endocrine therapy in patients
      with ER-positive breast cancer are ongoing.

PMID- 24663046
TI  - Follicular Dendritic Cell Sarcoma Presenting As a Thyroid Mass.

PMID- 24663047
TI  - Metastatic neuroblastoma confined to distant lymph nodes (stage 4N) predicts
      outcome in patients with stage 4 disease: A study from the International
      Neuroblastoma Risk Group Database.
AB  - PURPOSE: The presence of distant metastases is one of the most powerful
      predictors of outcome in patients with neuroblastoma. However, the pattern of
      metastatic spread is not incorporated into current risk stratification systems.
      Small case series have suggested that patients with neuroblastoma who have
      metastatic disease limited to distant lymph nodes (4N disease) may have improved
      outcomes. PATIENTS AND METHODS: We analyzed retrospective data from the
      International Neuroblastoma Risk Group database for patients diagnosed from 1990
      to 2002. 4N patients were compared with the remaining stage 4 patients (non-4N),
      excluding those with missing metastatic site data. RESULTS: In all, 2,250
      International Neuroblastoma Staging System stage 4 patients with complete data
      were identified, of whom 146 (6.5%) had 4N disease. For 4N patients, event-free
      survival (EFS; 5-year, 77% +/- 4%) and overall survival (OS; 5-year, 85% +/- 3%)
      were significantly better than EFS (5-year, 35% +/- 1%) and OS (5-year, 42% +/-
      1%) for non-4N stage 4 patients (P < .001). 4N patients were more likely to be
      younger (P < .001) and have tumors with favorable characteristics, including
      absence of MYCN amplification (89% v 69%; P < .001). In a multivariable analysis,
      4N disease remained a significant predictor of outcome (hazard ratio for non-4N v
      4N: 3.40 for EFS and 3.69 for OS). Within subgroups defined by age at diagnosis
      and tumor MYCN status, 4N disease was significantly associated with improved
      outcomes. CONCLUSION: 4N represents a subgroup with better outcome than that of
      other patients with metastatic disease. These findings suggest that the biology
      and treatment response of 4N tumors differ from other stage 4 tumors, and less
      intensive therapy should be considered for this cohort. Future exploration of
      biologic factors determining the pattern of metastatic spread is warranted.

PMID- 24663048
TI  - Sentinel lymph node biopsy for patients with early-stage breast cancer: American
      Society of Clinical Oncology clinical practice guideline update.
AB  - PURPOSE: To provide evidence-based recommendations to practicing oncologists,
      surgeons, and radiation therapy clinicians to update the 2005 clinical practice
      guideline on the use of sentinel node biopsy (SNB) for patients with early-stage
      breast cancer. METHODS: The American Society of Clinical Oncology convened an
      Update Committee of experts in medical oncology, pathology, radiation oncology,
      surgical oncology, guideline implementation, and advocacy. A systematic review of
      the literature was conducted from February 2004 to January 2013 in Medline.
      Guideline recommendations were based on the review of the evidence by Update
      Committee. RESULTS: This guideline update reflects changes in practice since the
      2005 guideline. Nine randomized clinical trials (RCTs) met systematic review
      criteria for clinical questions 1 and 2; 13 cohort studies informed clinical
      question 3. RECOMMENDATIONS: Women without sentinel lymph node (SLN) metastases
      should not receive axillary lymph node dissection (ALND). Women with one to two
      metastatic SLNs planning to undergo breast-conserving surgery with whole-breast
      radiotherapy should not undergo ALND (in most cases). Women with SLN metastases
      who will undergo mastectomy should be offered ALND. These three recommendation
      are based on RCTs. Women with operable breast cancer and multicentric tumors,
      with ductal carcinoma in situ (DCIS) who will undergo mastectomy, who previously
      underwent breast and/or axillary surgery, or who received
      preoperative/neoadjuvant systemic therapy may be offered SNB. Women who have
      large or locally advanced invasive breast cancer (tumor size T3/T4), inflammatory
      breast cancer, or DCIS (when breast-conserving surgery is planned) or are
      pregnant should not undergo SNB. These recommendations are based on cohort
      studies and/or informal consensus. In some cases, updated evidence was
      insufficient to update previous recommendations.

PMID- 24663050
TI  - Acute transient global ventricular dysfunction as the presenting symptom of
      anaplastic large-cell lymphoma.

PMID- 24663051
TI  - Conflicted confidence: academic oncologists' views on multiplex pharmacogenomic
      testing.

PMID- 24663049
TI  - Prolonged administration of azacitidine with or without entinostat for
      myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related
      changes: results of the US Leukemia Intergroup trial E1905.
AB  - PURPOSE: Although azacitidine (AZA) improves survival in patients with high-risk
      myelodysplastic syndrome, the overall response remains approximately 50%.
      Entinostat is a histone deacetylase inhibitor that has been combined with AZA
      with significant clinical activity in a previous phase I dose finding study.
      DESIGN: Open label phase II randomized trial comparing AZA 50 mg/m(2)/d given for
      10 days +/- entinostat 4 mg/m(2)/d day 3 and day 10. All subtypes of
      myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with
      myelodysplasia-related changes were eligible for the study. The primary objective
      was the rate of hematologic normalization (HN; complete remission + partial
      remission + trilineage hematological improvement). RESULTS: One hundred forty
      nine patients were analyzed, including 97 patients with myelodysplastic syndrome
      and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22%
      to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat
      group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia
      Group B 9221 trial), but only the AZA group fulfilled the primary objective of
      the study. Rates of overall hematologic response were 46% and 44%, respectively.
      Median overall survivals were 18 months for the AZA group and 13 months for the
      AZA + entinostat group. The combination arm led to less demethylation compared
      with the monotherapy arm, suggesting pharmacodynamic antagonism. CONCLUSION:
      Addition of entinostat to AZA did not increase clinical response as defined by
      the protocol and was associated with pharmacodynamic antagonism. However, the
      prolonged administration of AZA by itself seems to increase HN rate compared with
      standard dosing and warrants additional investigation.

PMID- 24663052
TI  - Paraneoplastic focal segmental glomerulosclerosis in sarcomatoid renal cell
      cancer.

PMID- 24663053
TI  - Milestones in the use of combined-modality radiation therapy and chemotherapy.

PMID- 24663054
TI  - Strongly enhanced current densities in Sr0.6K0.4Fe2As2 + Sn superconducting
      tapes.
AB  - Improving transport current has been the primary topic for practical application
      of superconducting wires and tapes. However, the porous nature of powder-in-tube
      (PIT) processed iron-based tapes is one of the important reasons for low critical
      current density (Jc) values. In this work, the superconducting core density of ex
      situ Sr0.6K0.4Fe2As2 + Sn tapes, prepared from optimized precursors, was
      significantly improved by employing a simple hot pressing as an alternative route
      for final sintering. The resulting samples exhibited optimal critical temperature
      (Tc), sharp resistive transition, small resistivity and high Vickers hardness
      (Hv) value. Consequently, the transport Jc reached excellent values of 5.1 *
      10(4) A/cm(2) in 10 T and 4.3 * 10(4) A/cm(2) in 14 T at 4.2 K, respectively. Our
      tapes also exhibited high upper critical field Hc2 and almost field-independent
      Jc. These results clearly demonstrate that PIT pnictide wire conductors are very
      promising for high-field magnet applications.

PMID- 24663055
TI  - Netrin-1 promotes epithelial sodium channel-mediated alveolar fluid clearance via
      activation of the adenosine 2B receptor in lipopolysaccharide-induced acute lung
      injury.
AB  - BACKGROUND: The epithelial sodium channel (ENaC) is the driving force for
      pulmonary edema absorption in acute lung injury (ALI). Netrin-1 is a newly found
      anti-inflammatory factor that works by activating the adenosine 2B receptor
      (A2BAR). Meanwhile, activated A2BAR has the potential to enhance ENaC-dependent
      alveolar fluid clearance (AFC). However, whether netrin-1 can increase ENaC
      mediated AFC by activating A2BAR remains unclear. OBJECTIVES: To investigate the
      effect of netrin-1 on AFC in ALI and clarify the pathway via which netrin-1
      regulates the expression of ENaC in vivo and in vitro. METHODS: An ALI model was
      established by intratracheal instillation of lipopolysaccharide (LPS; 5 mg/kg) in
      C57BL/J mice, followed by netrin-1 with or without pretreatment with PSB1115, via
      the caudal vein. Twenty-four hours later, the lungs were isolated for
      determination of the bronchoalveolar lavage fluid, the lung wet/dry weight (W/D)
      ratio, AFC, the expressions of alpha-, beta-, and gamma-ENaC, and cyclic
      adenosine monophosphate (cAMP) levels. LPS-stimulated MLE-12 cells were incubated
      with netrin-1 with or without preincubation with PSB1115. Twenty-four hours
      later, the expressions of alpha-, beta-, and gamma-ENaC were detected. RESULTS:
      In vivo, netrin-1 expression was significantly decreased during ALI. Substituted
      netrin-1 significantly dampened the lung injury, decreased the W/D ratio, and
      enhanced AFC, the expressions of alpha-, beta-, and gamma-ENaC, and cAMP levels
      in ALI, which were abolished by specific A2BAR inhibitor PSB1115. In vitro,
      netrin-1 increased the expressions of alpha-, beta-, and gamma-ENaC, which were
      prevented by PSB1115. CONCLUSION: These results indicate that netrin-1 dampens
      pulmonary inflammation and increases ENaC-mediated AFC to alleviate pulmonary
      edema in LPS-induced ALI by enhancing cAMP levels through the activation of
      A2BAR.

PMID- 24663056
TI  - A caspase-dependent pathway is involved in Wnt/beta-catenin signaling promoted
      apoptosis in Bacillus Calmette-Guerin infected RAW264.7 macrophages.
AB  - Apoptosis of alveolar macrophages following Mycobacterium tuberculosis infection
      have been demonstrated to play a central role in the pathogenesis of
      tuberculosis. In the present study, we found that Wnt/beta-catenin signaling
      possesses the potential to promote macrophage apoptosis in response to
      mycobacterial infection. In agreement with other findings, an activation Wnt/beta
      catenin signaling was observed in murine macrophage RAW264.7 cells upon
      Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection at a multiple-of
      infection of 10, which was accompanied with up-regulation of pro-inflammatory
      cytokines TNF-alpha and IL-6 production. However, the BCG-induced TNF-alpha and
      IL-6 secretion could be significantly reduced when the cells were exposed to a
      canonical Wnt signaling ligand, Wnt3a. Importantly, the activation of Wnt/beta
      catenin signaling was able to further promote apoptosis in BCG-infected RAW264.7
      cells in part by a mitochondria-dependent apoptosis pathway. Immunoblotting
      analysis further demonstrated that Wnt/beta-catenin signaling-induced cell
      apoptosis partly through a caspase-dependent apoptosis mechanism by down
      regulation of anti-apoptotic protein Mcl-1, and up-regulation of pro-apoptotic
      proteins Bax and cleaved-caspase-3, as well as enhancement of caspase-3 activity
      in BCG-infected RAW264.7 cells. These data may imply an underlying mechanism of
      alveolar macrophages in response to mycobacterial infection, by which the
      pathogen induces Wnt/beta-catenin signaling activation, which in turn represses
      mycobacterium-trigged inflammatory responses and promotes mycobacteria-infected
      cell apoptosis. 

PMID- 24663057
TI  - A chrysanthemum heat shock protein confers tolerance to abiotic stress.
AB  - Heat shock proteins are associated with protection against various abiotic
      stresses. Here, the isolation of a chrysanthemum cDNA belonging to the HSP70
      family is reported. The cDNA, designated CgHSP70, encodes a 647-residue
      polypeptide, of estimated molecular mass 70.90 kDa and pI 5.12. A sub-cellular
      localization assay indicated that the cDNA product is deposited in the cytoplasm
      and nucleus. The performance of Arabidopsis thaliana plants constitutively
      expressing CgHSP70 demonstrated that the gene enhances tolerance to heat, drought
      and salinity. When CgHSP70 was stably over-expressed in chrysanthemum, the plants
      showed an increased peroxidase (POD) activity, higher proline content and
      inhibited malondialdehyde (MDA) content. After heat stress, drought or salinity
      the transgenic plants were better able to recover, demonstrating CgHSP70 positive
      effect. 

PMID- 24663058
TI  - Differential transcriptome analysis between Paulownia fortunei and its
      synthesized autopolyploid.
AB  - Paulownia fortunei is an ecologically and economically important tree species
      that is widely used as timber and chemical pulp. Its autotetraploid, which
      carries a number of valuable traits, was successfully induced with colchicine. To
      identify differences in gene expression between P. fortunei and its synthesized
      autotetraploid, we performed transcriptome sequencing using an Illumina Genome
      Analyzer IIx (GAIIx). About 94.8 million reads were generated and assembled into
      383,056 transcripts, including 18,984 transcripts with a complete open reading
      frame. A conducted Basic Local Alignment Search Tool (BLAST) search indicated
      that 16,004 complete transcripts had significant hits in the National Center for
      Biotechnology Information (NCBI) non-redundant database. The complete transcripts
      were given functional assignments using three public protein databases. One
      thousand one hundred fifty eight differentially expressed complete transcripts
      were screened through a digital abundance analysis, including transcripts
      involved in energy metabolism and epigenetic regulation. Finally, the expression
      levels of several transcripts were confirmed by quantitative real-time PCR. Our
      results suggested that polyploidization caused epigenetic-related changes, which
      subsequently resulted in gene expression variation between diploid and
      autotetraploid P. fortunei. This might be the main mechanism affected by the
      polyploidization. Our results represent an extensive survey of the P. fortunei
      transcriptome and will facilitate subsequent functional genomics research in P.
      fortunei. Moreover, the gene expression profiles of P. fortunei and its
      autopolyploid will provide a valuable resource for the study of polyploidization.

PMID- 24663059
TI  - No stress! Relax! Mechanisms governing growth and shape in plant cells.
AB  - The mechanisms through which plant cells control growth and shape are the result
      of the coordinated action of many events, notably cell wall stress relaxation and
      turgor-driven expansion. The scalar nature of turgor pressure would drive plant
      cells to assume spherical shapes; however, this is not the case, as plant cells
      show an amazing variety of morphologies. Plant cell walls are dynamic structures
      that can display alterations in matrix polysaccharide composition and
      concentration, which ultimately affect the wall deformation rate. The wide
      varieties of plant cell shapes, spanning from elongated cylinders (as pollen
      tubes) and jigsaw puzzle-like epidermal cells, to very long fibres and branched
      stellate leaf trichomes, can be understood if the underlying mechanisms
      regulating wall biosynthesis and cytoskeletal dynamics are addressed. This review
      aims at gathering the available knowledge on the fundamental mechanisms
      regulating expansion, growth and shape in plant cells by putting a special
      emphasis on the cell wall-cytoskeleton system continuum. In particular, we
      discuss from a molecular point of view the growth mechanisms characterizing cell
      types with strikingly different geometries and describe their relationship with
      primary walls. The purpose, here, is to provide the reader with a comprehensive
      overview of the multitude of events through which plant cells manage to expand
      and control their final shapes. 

PMID- 24663060
TI  - Synthesis and biological evaluation of 2-aminobenzamide derivatives as
      antimicrobial agents: opening/closing pharmacophore site.
AB  - A series of new 2-aminobenzamide derivatives (1-10) has been synthesized in good
      to excellent yields by adopting both conventional and/or a time-efficient
      microwave assisted methodologies starting from isatoic anhydride (ISA) and
      characterized on the basis of their physical, spectral and microanalytical data.
      Selected compounds of this series were then tested against various bacterial
      (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106).
      Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and
      fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus
      (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as
      antimicrobial agents. Compound 5 was found to be the most active compound among
      those tested, which showed excellent antifungal activity against Aspergillus
      fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to
      good antibacterial and antifungal activity against most of the other strains of
      bacteria and fungi. Furthermore, potential pharmacophore sites were identified
      and their activity was related with the structures in the solution. 

PMID- 24663061
TI  - Fast and accurate multivariate Gaussian modeling of protein families: predicting
      residue contacts and protein-interaction partners.
AB  - In the course of evolution, proteins show a remarkable conservation of their
      three-dimensional structure and their biological function, leading to strong
      evolutionary constraints on the sequence variability between homologous proteins.
      Our method aims at extracting such constraints from rapidly accumulating sequence
      data, and thereby at inferring protein structure and function from sequence
      information alone. Recently, global statistical inference methods (e.g. direct
      coupling analysis, sparse inverse covariance estimation) have achieved a
      breakthrough towards this aim, and their predictions have been successfully
      implemented into tertiary and quaternary protein structure prediction methods.
      However, due to the discrete nature of the underlying variable (amino-acids),
      exact inference requires exponential time in the protein length, and efficient
      approximations are needed for practical applicability. Here we propose a very
      efficient multivariate Gaussian modeling approach as a variant of direct-coupling
      analysis: the discrete amino-acid variables are replaced by continuous Gaussian
      random variables. The resulting statistical inference problem is efficiently and
      exactly solvable. We show that the quality of inference is comparable or superior
      to the one achieved by mean-field approximations to inference with discrete
      variables, as done by direct-coupling analysis. This is true for (i) the
      prediction of residue-residue contacts in proteins, and (ii) the identification
      of protein-protein interaction partner in bacterial signal transduction. An
      implementation of our multivariate Gaussian approach is available at the website
      http://areeweb.polito.it/ricerca/cmp/code. 

PMID- 24663062
TI  - Adaptive gene regulation in the Striatum of RGS9-deficient mice.
AB  - BACKGROUND: RGS9-deficient mice show drug-induced dyskinesia but normal locomotor
      activity under unchallenged conditions. RESULTS: Genes related to Ca2+ signaling
      and their functions were regulated in RGS9-deficient mice. CONCLUSION: Changes in
      Ca2+ signaling that compensate for RGS9 loss-of-function can explain the normal
      locomotor activity in RGS9-deficient mice under unchallenged conditions.
      SIGNIFICANCE: Identified signaling components may represent novel targets in
      antidyskinetic therapy. The long splice variant of the regulator of G-protein
      signaling 9 (RGS9-2) is enriched in striatal medium spiny neurons and dampens
      dopamine D2 receptor signaling. Lack of RGS9-2 can promote while its
      overexpression prevents drug-induced dyskinesia. Other animal models of drug
      induced dyskinesia rather pointed towards overactivity of dopamine receptor
      mediated signaling. To evaluate changes in signaling pathways mRNA expression
      levels were determined and compared in wild-type and RGS9-deficient mice.
      Unexpectedly, expression levels of dopamine receptors were unchanged in RGS9
      deficient mice, while several genes related to Ca2+ signaling and long-term
      depression were differentially expressed when compared to wild type animals.
      Detailed investigations at the protein level revealed hyperphosphorylation of
      DARPP32 at Thr34 and of ERK1/2 in striata of RGS9-deficient mice. Whole cell
      patch clamp recordings showed that spontaneous synaptic events are increased
      (frequency and size) in RGS9-deficient mice while long-term depression is reduced
      in acute brain slices. These changes are compatible with a Ca2+-induced
      potentiation of dopamine receptor signaling which may contribute to the drug
      induced dyskinesia in RGS9-deficient mice.

PMID- 24663064
TI  - The value of healthcare data in ophthalmology.
AB  - PURPOSE OF REVIEW: The healthcare system creates a vast amount of data that are
      utilized by a wide variety of entities for a multitude of purposes. Physicians
      have traditionally been unable to control who has access to their data or how
      their data are used. The widespread adoption of the Electronic Health Record
      (EHR) by physicians will create a larger and more valuable healthcare data market
      with broad implications for the healthcare system. It is, therefore, important
      for physicians to understand the evolving healthcare data market and the
      importance of maintaining ownership of and control over their electronic health
      data. RECENT FINDINGS: Several entities, including private health insurance
      companies, federal payers, medical societies, and pharmaceutical companies are
      increasingly utilizing healthcare data to drive reimbursement policies and
      commercial initiatives. SUMMARY: Given the critical importance that EHR data will
      play in multiple aspects of the healthcare industry, it is in physicians'
      interest to maintain ownership and control of the healthcare data that they
      generate. It would be prudent for physicians to exercise caution before
      relinquishing data rights to entities that may sell the data to payers or other
      customers with whom physicians' interests may not be aligned.

PMID- 24663063
TI  - Differences in the gene expression profiles of haemocytes from schistosome
      susceptible and -resistant biomphalaria glabrata exposed to Schistosoma mansoni
      excretory-secretory products.
AB  - During its life cycle, the helminth parasite Schistosoma mansoni uses the
      freshwater snail Biomphalaria glabrata as an intermediate host to reproduce
      asexually generating cercariae for infection of the human definitive host.
      Following invasion of the snail, the parasite develops from a miracidium to a
      mother sporocyst and releases excretory-secretory products (ESPs) that likely
      influence the outcome of host infection. To better understand molecular
      interactions between these ESPs and the host snail defence system, we determined
      gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible
      strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 MUg/ml) for 1 h,
      using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found
      differentially expressed between haemocytes from the two snail strains, 57
      resistant specific and 41 susceptible specific, 60 of which had no known
      homologue in GenBank. Known differentially expressed resistant-snail genes
      included the nuclear factor kappa B subunit Relish, elongation factor 1alpha, 40S
      ribosomal protein S9, and matrilin; known susceptible-snail specific genes
      included cathepsins D and L, and theromacin. Comparative analysis with other gene
      expression studies revealed 38 of the 98 identified genes to be uniquely
      differentially expressed in haemocytes in the presence of ESPs, thus identifying
      for the first time schistosome ESPs as important molecules that influence global
      snail host-defence cell gene expression profiles. Such immunomodulation may
      benefit the schistosome, enabling its survival and successful development in the
      snail host. 

PMID- 24663065
TI  - Long-term longitudinal study of patients treated with ranibizumab for neovascular
      age-related macular degeneration.
AB  - PURPOSE OF REVIEW: To review the current literature regarding long-term treatment
      beyond 2 years with anti-vascular endothelial growth factor (VEGF) inhibition for
      neovascular age-related macular degeneration (nv-AMD). RECENT FINDINGS: Only few
      studies of anti-VEGF treatment for nv-AMD exist beyond 2 years, and the number of
      patients followed for 4 years or longer is small. The results of studies show
      that the majority of patients with nv-AMD can preserve visual acuity compared
      with baseline, subgroups reveal large variations in visual benefit. Approximately
      20-30% of patients seem to respond poorly to the treatment, and 20% obtain a
      condition with inactivity and good results. The majority of patients will need
      continuous active treatment. Long-term decline of visual acuity reflects the
      natural progression of the disease, however, insufficient treatment cannot be
      excluded leaving a potential for further improvement. Close follow-up to detect
      recurrent activity of nv-AMD and activity in fellow eye is important. Definitive
      evidence of systemic side-effects is lacking, but long-term VEGF inhibition seems
      to be tolerated well with few ocular and systemic complications. SUMMARY: The
      majority of patients with nv-AMD can preserve visual acuity and expect long-term
      treatment beyond 2 years. Ocular complications and systemic adverse events remain
      few.

PMID- 24663066
TI  - Pan retinal photocoagulation for proliferative diabetic retinopathy: pattern scan
      laser versus argon laser.
AB  - PURPOSE OF REVIEW: Diabetic retinopathy is the leading cause of visual impairment
      in working-age adults worldwide. Pan retinal photocoagulation (PRP) has provided
      an effective treatment to decrease the risk of severe vision loss in patients
      with proliferative diabetic retinopathy for the past four decades. Pattern scan
      laser (PASCAL) was developed to minimize the side effects of PRP. The purpose of
      this review is to discuss the differences between the traditional argon laser and
      the PASCAL. RECENT FINDINGS: PASCAL can achieve comparable results with the
      conventional argon PRP in the treatment of patients with diabetic retinopathy.
      The PASCAL delivery system creates well aligned arrays of retinal lesions in a
      shorter period. PASCAL provides amore comfortable profile when compared to the
      argon laser. SUMMARY: The PASCAL is now being substituted for the conventional
      argon laser for PRP in many clinics. Ophthalmologists should keep in mind that
      adjusting the PASCAL settings (including the duration, number, and size of laser
      burns) might become necessary to maintain regression and eliminate recurrence of
      neovascularization in patients with proliferative diabetic retinopathy. Further
      studies are needed to determine the parameters for optimal safety and efficacy on
      the PASCAL.

PMID- 24663067
TI  - Recent advances in the design of artificial corneas.
AB  - PURPOSE OF REVIEW: Artificial corneas are being developed to meet a shortage of
      donor corneas and to address cases in which allografting is contraindicated. A
      range of artificial corneas has been developed. Here we review several newer
      designs and especially those inspired by naturally occurring biomaterials found
      with the human body and elsewhere. RECENT FINDINGS: Recent trends in the
      development of artificial corneas indicate a move towards the use of materials
      derived from native sources including decellularized corneal tissue and tissue
      substitutes synthesized by corneal cells in vitro when grown either on their own
      or in conjunction with novel protein-based scaffolds. Biologically inspired
      materials are also being considered for implantation on their own with the view
      to promoting endogenous corneal tissue. SUMMARY: More recent attempts at making
      artificial corneas have taken a more nature-based or nature-inspired approach.
      Several will in the near future be likely to be available clinically.

PMID- 24663068
TI  - Intensity of territorial marking predicts wolf reproduction: implications for
      wolf monitoring.
AB  - BACKGROUND: The implementation of intensive and complex approaches to monitor
      large carnivores is resource demanding, restricted to endangered species, small
      populations, or small distribution ranges. Wolf monitoring over large spatial
      scales is difficult, but the management of such contentious species requires
      regular estimations of abundance to guide decision-makers. The integration of
      wolf marking behaviour with simple sign counts may offer a cost-effective
      alternative to monitor the status of wolf populations over large spatial scales.
      METHODOLOGY/PRINCIPAL FINDINGS: We used a multi-sampling approach, based on the
      collection of visual and scent wolf marks (faeces and ground scratching) and the
      assessment of wolf reproduction using howling and observation points, to test
      whether the intensity of marking behaviour around the pup-rearing period (summer
      autumn) could reflect wolf reproduction. Between 1994 and 2007 we collected 1,964
      wolf marks in a total of 1,877 km surveyed and we searched for the pups' presence
      (1,497 howling and 307 observations points) in 42 sampling sites with a regular
      presence of wolves (120 sampling sites/year). The number of wolf marks was ca. 3
      times higher in sites with a confirmed presence of pups (20.3 vs. 7.2 marks). We
      found a significant relationship between the number of wolf marks (mean and
      maximum relative abundance index) and the probability of wolf reproduction.
      CONCLUSIONS/SIGNIFICANCE: This research establishes a real-time relationship
      between the intensity of wolf marking behaviour and wolf reproduction. We suggest
      a conservative cutting point of 0.60 for the probability of wolf reproduction to
      monitor wolves on a regional scale combined with the use of the mean relative
      abundance index of wolf marks in a given area. We show how the integration of
      wolf behaviour with simple sampling procedures permit rapid, real-time, and cost
      effective assessments of the breeding status of wolf packs with substantial
      implications to monitor wolves at large spatial scales.

PMID- 24663069
TI  - Acute leukemia cytochemically myeloid and immunophenotypically T lymphoid.

PMID- 24663070
TI  - Extramedullary Tumor of Cerebral Falx: An Unusual Presentation of Acute
      Megakaryocytic Leukemia.
AB  - In childhood acute myelogenous leukemia, extramedullary tumor is an occasional
      clinical symptom. However, extramedullary acute megakaryocytic leukemia is
      extremely rare. Here, we report an extremely rare case of acute megakaryocytic
      leukemia in a patient who presented with extramedullary tumor of cerebral falx as
      a first manifestation before the diagnosis of systemic bone marrow leukemia. 

PMID- 24663071
TI  - Oral pyogenic granuloma in hemophilia: a report of 2 cases.
AB  - Pyogenic granulomas (PGs) are benign vascular lesions occurring in skin and
      mucous membranes, often secondary to trauma or chronic inflammation. Oral PGs
      have never been described previously in hemophilia. We describe 2 pediatric
      patients with hemophilia A, who developed PGs with inadequate factor therapy for
      bleeding. PG pathophysiology suggests an association with hemophilia given
      chronic vascular damage and low-grade inflammation at sites of bleeding in
      hemophilia patients. Knowledge about the occurrence of PGs in hemophilia patients
      is essential for prompt diagnosis and early institution of factor therapy, which
      in turn allows more rapid cessation of bleeding and lesion involution. 

PMID- 24663072
TI  - Good response to chemotherapy spares irradiation for extrarenal rhabdoid tumor
      conferring better activities of daily living.
AB  - A 7-year-old girl with stage IIA extrarenal rhabdoid tumor near the left cubital
      fossa received preoperative chemotherapy and surgical resection with median nerve
      reconstruction followed by postoperative high-dose chemotherapy. As preoperative
      chemotherapy resulted in decreased tumor size, disappearance of
      fluorodeoxyglucose-uptake, and pathologic complete response with total tumor
      resection, irradiation was successfully spared to avoid injury to the
      reconstructed nerve and inhibition of normal bone development. Two years after
      diagnosis, recurrence has not been observed and median nerve palsy is improving.
      This case suggests that radiation therapy could be spared for clinically and
      pathologically chemotherapy-good-responders in case total surgical resection is
      achieved.

PMID- 24663073
TI  - T-cell ALL in ataxia telangiectasia cured with only 7 weeks of anti-leukemic
      therapy.
AB  - A 20-month-old girl diagnosed with T-cell acute lymphoblastic leukemia was
      treated according to the Nordic NOPHO ALL2000 protocol. The patient developed
      severe immunosuppression and experienced life-threatening adenovirus infection,
      which was treated with ribavirin and cidofovir. alpha-fetoprotein was 20- to 30
      fold elevated, and genetic analysis confirmed the diagnosis of ataxia
      telangiectasia. Despite receiving only 7 weeks of anti-leukemic therapy, she has
      stayed in first remission now 8 years after the diagnosis. We speculate that this
      could be because of increased chemosensitivity of ATM-mutated leukemic cells,
      adenovirus causing a direct oncolytic effect, and/or high levels of endogenous
      cortisol during her severe infection. 

PMID- 24663074
TI  - A mechanical-force-driven physical vapour deposition approach to fabricating
      complex hydride nanostructures.
AB  - Nanoscale hydrides desorb and absorb hydrogen at faster rates and lower
      temperatures than bulk hydrides because of their high surface areas, abundant
      grain boundaries and short diffusion distances. No current methods exist for the
      direct fabrication of nanoscale complex hydrides (for example, alanates,
      borohydrides) with unique morphologies because of their extremely high
      reducibility, relatively low thermodynamic stability and complicated elemental
      composition. Here, we demonstrate a mechanical-force-driven physical vapour
      deposition procedure for preparing nanoscale complex hydrides without scaffolds
      or supports. Magnesium alanate nanorods measuring 20-40 nm in diameter and
      lithium borohydride nanobelts measuring 10-40 nm in width are successfully
      synthesised on the basis of the one-dimensional structure of the corresponding
      organic coordination polymers. The dehydrogenation kinetics of the magnesium
      alanate nanorods are improved, and the nanorod morphology persists through the
      dehydrogenation-hydrogenation process. Our findings may facilitate the
      fabrication of such hydrides with improved hydrogen storage properties for
      practical applications. 

PMID- 24663075
TI  - A recombinant novirhabdovirus presenting at the surface the E Glycoprotein from
      West Nile Virus (WNV) is immunogenic and provides partial protection against
      lethal WNV challenge in BALB/c mice.
AB  - West Nile Virus (WNV) is a zoonotic mosquito-transmitted flavivirus that can
      infect and cause disease in mammals including humans. Our study aimed at
      developing a WNV vectored vaccine based on a fish Novirhabdovirus, the Viral
      Hemorrhagic Septicemia virus (VHSV). VHSV replicates at temperatures lower than
      20 degrees C and is naturally inactivated at higher temperatures. A reverse
      genetics system has recently been developed in our laboratory for VHSV allowing
      the addition of genes in the viral genome and the recovery of the respective
      recombinant viruses (rVHSV). In this study, we have generated rVHSV vectors
      bearing the complete WNV envelope gene (EWNV) (rVHSV-EWNV) or fragments encoding
      E subdomains (either domain III alone or domain III fused to domain II) (rVHSV
      DIIIWNV and rVHSV-DII-DIIIWNV, respectively) in the VHSV genome between the N and
      P cistrons. With the objective to enhance the targeting of the EWNV protein or
      EWNV-derived domains to the surface of VHSV virions, Novirhadovirus G-derived
      signal peptide and transmembrane domain (SPG and TMG) were fused to EWNV at its
      amino and carboxy termini, respectively. By Western-blot analysis, electron
      microscopy observations or inoculation experiments in mice, we demonstrated that
      both the EWNV and the DIIIWNV could be expressed at the viral surface of rVHSV
      upon addition of SPG. Every constructs expressing EWNV fused to SPG protected 40
      to 50% of BALB/cJ mice against WNV lethal challenge and specifically rVHSV
      SPGEWNV induced a neutralizing antibody response that correlated with protection.
      Surprisingly, rVHSV expressing EWNV-derived domain III or II and III were unable
      to protect mice against WNV challenge, although these domains were highly
      incorporated in the virion and expressed at the viral surface. In this study we
      demonstrated that a heterologous glycoprotein and non membrane-anchored protein,
      can be efficiently expressed at the surface of rVHSV making this approach
      attractive to develop new vaccines against various pathogens. 

PMID- 24663076
TI  - Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations
      and clinical improvement in children and adolescent patients.
AB  - There is little known about pharmacogenetic of fluoxetine in children and
      adolescents. In this study, we evaluate, for the first time, the influence of
      CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of
      fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical
      improvement in children and adolescent patients receiving fluoxetine treatment.
      The assessment was performed in 83 patients after 8 and 12 weeks of treatment.
      Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of
      active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1
      polymorphism, T allele carriers showed significantly higher improvements on the
      majority of scales including the Clinical Global Impression-Improvement scale
      (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in
      fluoxetine pharmacokinetics and provide evidence for the potential effect of the
      ABCB1 genotype on the clinical improvement in children and adolescent patients
      treated with fluoxetine. 

PMID- 24663077
TI  - Clinical impact of the HGF/MET pathway activation in patients with advanced
      gastric cancer treated with palliative chemotherapy.
AB  - In gastric cancer, available clinical studies focusing on the activated
      hepatocyte growth factor (HGF)/MET pathway are limited to surgical and often
      heterogeneous series. MET copy number gain (CNG) and an activating truncation in
      the HGF promoter (deoxyadenosine tract element, DATE+) were studied in tumors of
      95 patients with advanced gastric cancer treated with palliative chemotherapy.
      Associations with overall survival (OS) and the pattern of metastatic disease
      were studied. Median OS was 9.7 months in 80 MET CNG <5 copies cases (MET-), and
      6.4 months in 15 MET CNG was ?5 copies cases (MET+) (P=0.001). MET+ status
      confirmed the adverse prognostic effect in the multivariate model. A
      significantly different distribution of MET+/DATE+ and MET-/DATE- cases was
      observed between patients with and without peritoneal carcinomatosis (PC). MET+
      status confirms its adverse prognostic role in advanced gastric cancer patients.
      The activated MET/HGF axis seems to be associated with PC. These findings are
      relevant to the development of anti-MET/HGF compounds. 

PMID- 24663079
TI  - Tris-thiourea tripodal-based molecules as chloride transmembrane transporters:
      insights from molecular dynamics simulations.
AB  - The interaction of six tripodal synthetic chloride transmembrane transporters
      with a POPC bilayer was investigated by means of molecular dynamics simulations
      using the general Amber force field (GAFF) for the transporters and the LIPID11
      force field for phospholipids. These transporters are structurally simple
      molecules, based on the tris(2-aminoethyl)amine scaffold, containing three
      thiourea binding units coupled with three n-butyl (1), phenyl (2), fluorophenyl
      (3), pentafluorophenyl (4), trifluoromethylphenyl (5), or
      bis(trifluoromethyl)phenyl (6) substituents. The passive diffusion of 1-6? Cl(-)
      was evaluated with the complexes initially positioned either in the water phase
      or inside the bilayer. In the first scenario the chloride is released in the
      water solution before the synthetic molecules achieve the water-lipid interface
      and permeate the membrane. In the latter one, only when the chloride complex
      reaches the interface is the anion released to the water phase, with the
      transporter losing the initial ggg tripodal shape. Independently of the
      transporter used in the membrane system, the bilayer structure is preserved and
      the synthetic molecules interact with the POPC molecules at the phosphate
      headgroup level, via N-H...O hydrogen bonds. Overall, the molecular dynamics
      simulations' results indicate that the small tripodal molecules in this series
      have a low impact on the bilayer and are able to diffuse with chloride inside the
      lipid environment. Indeed, these are essential conditions for these molecules to
      promote the transmembrane transport as anion carriers, in agreement with
      experimental efflux data.

PMID- 24663078
TI  - Function and localization of the Arabidopsis thaliana diacylglycerol
      acyltransferase DGAT2 expressed in yeast.
AB  - Diacylglycerol acyltransferases (DGATs) catalyze the final and only committed
      step of triacylglycerol synthesis. DGAT activity is rate limiting for
      triacylglycerol accumulation in mammals, plants and microbes. DGATs belong to
      three different evolutionary classes. In Arabidopsis thaliana, DGAT1, encoded by
      At2g19450, is the major DGAT enzyme involved in triacylglycerol accumulation in
      seeds. Until recently, the function of DGAT2 (At3g51520) has remained elusive.
      Previous attempts to characterize its enzymatic function by heterologous
      expression in yeast were unsuccessful. In the present report we demonstrate that
      expression of a codon-optimized version of the DGAT2 gene is able to restore
      neutral lipid accumulation in the Saccharomyces cerevisiae mutant strain (H1246),
      which is defective in triacylglycerol biosynthesis. Heterologous expression of
      codon-optimized DGAT2 and DGAT1 induced the biogenesis of subcellular lipid
      droplets containing triacylglycerols and squalene. Both DGAT proteins were found
      to be associated with these lipid droplets. The fatty acid composition was
      affected by the nature of the acyltransferase expressed. DGAT2 preferentially
      incorporated C16:1 fatty acids whereas DGAT1 displayed preference for C16:0,
      strongly suggesting that these enzymes have contrasting substrate specificities. 

PMID- 24663080
TI  - Perineural dexmedetomidine attenuates inflammation in rat sciatic nerve via the
      NF-kappaB pathway.
AB  - Recent studies have shown that dexmedetomidine exerts an anti-inflammatory effect
      by reducing serum levels of inflammatory factors, however, the up-stream
      mechanism is still unknown. The transcription factor NF-kappaB enters the nucleus
      and promotes the transcription of its target genes, including those encoding the
      pro-inflammatory cytokines IL-6 and TNF-alpha. In this study, we established a
      rat model that simulates a clinical surgical procedure to investigate the anti
      inflammatory effect of perineural administration of dexmedetomidine and the
      underlying mechanism. Dexmedetomidine reduced the sciatic nerve levels of IL-6
      and TNF-alpha at both the mRNA and protein level. Dexmedetomidine also inhibited
      the translocation of activated NF-kappaB to the nucleus and the binding activity
      of NF-kappaB. The anti-inflammatory effect is confirmed to be dose-dependent.
      Finally, pyrrolidine dithiocarbamate also reduced the levels of IL-6 and TNF
      alpha and the activation of NF-kappaB. In conclusion, dexmedetomidine inhibited
      the nuclear translocation and binding activity of activated NF-kappaB, thus
      reducing inflammatory cytokines. 

PMID- 24663081
TI  - Long non-coding RNA HOTAIR promotes cell migration and invasion via down
      regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells.
AB  - Long non-coding RNA HOTAIR exerts regulatory functions in various biological
      processes in cancer cells, such as proliferation, apoptosis, mobility, and
      invasion. We previously found that HOX transcript antisense RNA (HOTAIR) is a
      negative prognostic factor and exhibits oncogenic activity in hepatocellular
      carcinoma (HCC). In this study, we aimed to investigate the role and molecular
      mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we
      profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel
      7402 HCC cell line. The results showed that 129 genes were significantly down
      regulated, while 167 genes were significantly up-regulated (fold change >2, p <
      0.05). Bioinformatics analysis indicated that RNA binding proteins were involved
      in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and
      Bel-7402 cells increased the mRNA and protein expression levels of RNA binding
      motif protein 38 (RBM38). Moreover, the expression levels of RBM38 in HCC
      specimens were significantly lower than paired adjacent noncancerous tissues. In
      addition, knockdown of HOTAIR resulted in a decrease of cell migration and
      invasion, which could be specifically rescued by down-regulation of RBM38. Taken
      together, HOTAIR could promote migration and invasion of HCC cells by inhibiting
      RBM38, which indicated critical roles of HOTAIR and RBM38 in HCC progression. 

PMID- 24663082
TI  - Influence of diet, menstruation and genetic factors on iron status: a cross
      sectional study in Spanish women of childbearing age.
AB  - The aim of this study was to investigate the combined influence of diet,
      menstruation and genetic factors on iron status in Spanish menstruating women (n
      = 142). Dietary intake was assessed by a 72-h detailed dietary report and
      menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss
      Coefficient (MBLC). Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf
      gene); rs1375515 (CACNA2D3 gene); and rs1800562 and rs1799945 (HFE gene,
      mutations C282Y and H63D, respectively). Iron biomarkers were determined and
      cluster analysis was performed. Differences among clusters in dietary intake,
      menstrual blood loss parameters and genotype frequencies distribution were
      studied. A categorical regression was performed to identify factors associated
      with cluster belonging. Three clusters were identified: women with poor iron
      status close to developing iron deficiency anemia (Cluster 1, n = 26); women with
      mild iron deficiency (Cluster 2, n = 59) and women with normal iron status
      (Cluster 3, n = 57). Three independent factors, red meat consumption, MBLC and
      mutation C282Y, were included in the model that better explained cluster
      belonging (R2 = 0.142, p < 0.001). In conclusion, the combination of high red
      meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect
      from iron deficiency in women of childbearing age. These findings could be useful
      to implement adequate strategies to prevent iron deficiency anemia.

PMID- 24663083
TI  - Endogenous nitric-oxide synthase inhibitor ADMA after acute brain injury.
AB  - Previous results on nitric oxide (NO) metabolism after traumatic brain injury
      (TBI) show variations in NO availability and controversial effects of exogenous
      nitric oxide synthase (NOS)-inhibitors. Furthermore, elevated levels of the
      endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) were reported in
      cerebro-spinal fluid (CSF) after traumatic subarachnoid hemorrhage (SAH).
      Therefore, we examined whether ADMA and the enzymes involved in NO- and ADMA
      metabolism are expressed in brain tissue after TBI and if time-dependent changes
      occur. TBI was induced by controlled cortical impact injury (CCII) and
      neurological performance was monitored. Expression of NOS, ADMA, dimethylarginine
      dimethylaminohydrolases (DDAH) and protein-arginine methyltransferase 1 (PRMT1)
      was determined by immunostaining in different brain regions and at various time
      points after CCII. ADMA and PRMT1 expression decreased in all animals after TBI
      compared to the control group, while DDAH1 and DDAH2 expression increased in
      comparison to controls. Furthermore, perilesionally ADMA is positively correlated
      with neuroscore performance, while DDAH1 and DDAH2 are negatively correlated.
      ADMA and its metabolizing enzymes show significant temporal changes after TBI and
      may be new targets in TBI treatment. 

PMID- 24663084
TI  - Application of computational methods for the design of BACE-1 inhibitors:
      validation of in silico modelling.
AB  - beta-Secretase (BACE-1) constitutes an important target for search of anti
      Alzheimer's drugs. The first inhibitors of this enzyme were peptidic compounds
      with high molecular weight and low bioavailability. Therefore, the search for new
      efficient non-peptidic inhibitors has been undertaken by many scientific groups.
      We started our work from the development of in silico methodology for the design
      of novel BACE-1 ligands. It was validated on the basis of crystal structures of
      complexes with inhibitors, redocking, cross-docking and training/test sets of
      reference ligands. The presented procedure of assessment of the novel compounds
      as beta-secretase inhibitors could be widely used in the design process. 

PMID- 24663085
TI  - Structure and antitumor and immunomodulatory activities of a water-soluble
      polysaccharide from Dimocarpus longan pulp.
AB  - A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted
      and successfully purified from Dimocarpus longan pulp via diethylaminoethyl
      (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The
      chemical structure was determined using Infrared (IR), gas chromatography (GC)
      and nuclear magnetic resonance (NMR) analysis. The results indicated that the
      molecular weight of the sample was 1.1 * 10(5) Da. Monosaccharide composition
      analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar
      ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of
      a backbone of -> 4)-alpha-D-Glcp-(1 -> 4)-alpha-D-GALPA-(1 -> 4)-alpha-D-Glcp-(1 
      > 4)-beta-D-Glcp-(1 -> units with poly saccharide side chains composed of -> 2)
      beta-D-Fruf-(1 -> 2)-L-sorbose-(1 -> attached to the O-6 position of the alpha-D
      Glcp residues. In vitro experiments indicated that LP1 had significantly high
      antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition
      percentages of 40% and 50%, respectively. In addition, LP1 significantly
      stimulated the production of the cytokine interferon-gamma (IFN-gamma), increased
      the activity of murine macrophages and enhanced B- and T-lymphocyte
      proliferation. The results of this study demonstrate that LP1 has potential
      applications as a natural antitumor agent with immunomodulatory activity.

PMID- 24663086
TI  - Albumin suppresses human hepatocellular carcinoma proliferation and the cell
      cycle.
AB  - Many investigations have revealed that a low recurrence rate of hepatocellular
      carcinoma (HCC) is associated with high serum albumin levels in patients;
      therefore, high levels of serum albumin are a major indicator of a favorable
      prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet
      been elucidated, so we investigated the effect of serum albumin on HCC cell
      proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human
      albumin. As control samples, Prionex was added to generate the same osmotic
      pressure as albumin. After 24-h incubation, the expressions of alpha-fetoprotein
      (AFP), p53, p21, and p57 were evaluated with real-time PCR using total RNA
      extracted from the liver. Protein expressions and the phosphorylation of Rb
      (retinoblastoma) were determined by Western blot analysis using total protein
      extracted from the liver. For flow cytometric analysis of the cell cycle, FACS
      analysis was performed. The percentages of cell cycle distribution were evaluated
      by PI staining, and all samples were analyzed employing FACScalibur (BD) with
      appropriate software (ModFit LT; BD). The cell proliferation assay was performed
      by counting cells with using a Scepter handy automated cell counter (Millipore).
      The mRNA levels of AFP relative to Alb(-): Alb(-), Alb(+), and Prionex, were 1,
      0.7 +/- 0.2 (p < 0.001 for Alb(-)), and 1 +/- 0.3, respectively. The mRNA levels
      of p21 were 1, 1.58 +/- 0.4 (p = 0.007 for Alb(-) and p = 0.004 for Prionex), and
      0.8 +/- 0.2, respectively. The mRNA levels of p57 were 1, 4.4 +/- 1.4 (p = 0.002
      for Alb(-) and Prionex), and 1.0 +/- 0.1, respectively. The protein expression
      levels of Rb were similar in all culture media. The phosphorylation of P807/811
      and P780 of Rb protein was reduced in Alb(+). More cells in the G0/G1 phase and
      fewer cells in S and G2/M phases were obtained in Alb(+) than in Alb(-) (G0/G1:
      60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(-),
      Alb(+), Prionex, respectively). The same results were obtained in HepG2. Cell
      proliferation was inhibited in 5 g/dL albumin medium in both HepG2 cells and
      Hep3B cells in 24 h culture by counting cell numbers. The presence of albumin in
      serum reduces the phosphorylation of Rb proteins and enhances the expression of
      p21 and p57, following an increase in the G0/G1 cell population, and suppresses
      cell proliferation. These results suggest that albumin itself suppresses the
      proliferation of hepatocellular carcinoma. 

PMID- 24663087
TI  - Identification of proteins of altered abundance in oil palm infected with
      Ganoderma boninense.
AB  - Basal stem rot is a common disease that affects oil palm, causing loss of yield
      and finally killing the trees. The disease, caused by fungus Ganoderma boninense,
      devastates thousands of hectares of oil palm plantings in Southeast Asia every
      year. In the present study, root proteins of healthy oil palm seedlings, and
      those infected with G. boninense, were analyzed by 2-dimensional gel
      electrophoresis (2-DE). When the 2-DE profiles were analyzed for proteins, which
      exhibit consistent significant change of abundance upon infection with G.
      boninense, 21 passed our screening criteria. Subsequent analyses by mass
      spectrometry and database search identified caffeoyl-CoA O-methyltransferase,
      caffeic acid O-methyltransferase, enolase, fructokinase, cysteine synthase,
      malate dehydrogenase, and ATP synthase as among proteins of which abundances were
      markedly altered. 

PMID- 24663089
TI  - Risk factors. Childhood exposure to parental smoking confers lifelong increase in
      cardiovascular risk.

PMID- 24663088
TI  - Robotic technology in cardiovascular medicine.
AB  - Robotic technology has been used in cardiovascular medicine since the late 1990s.
      Interventional cardiology, electrophysiology, endovascular surgery, minimally
      invasive cardiac surgery, and laparoscopic vascular surgery are all fields of
      application. Robotic devices enable endoscopic reconstructive surgery in narrow
      spaces and fast, very precise placement of catheters and devices in catheter
      based interventions. In all robotic systems, the operator manipulates the robotic
      arms from a control station or console. In the field of cardiac surgery, mitral
      valve repair, CABG surgery, atrial septal defect repair, and myxoma resection can
      be achieved using robotic technology. Furthermore, vascular surgeons can perform
      a variety of robotically assisted operations to treat aortic, visceral, and
      peripheral artery disease. In electrophysiology, ablation procedures for atrial
      fibrillation can be carried out with robotic support. In the past few years,
      robotically assisted percutaneous coronary intervention and abdominal aortic
      endovascular surgery techniques have been developed. The basic feasibility and
      safety of robotic approaches in cardiovascular medicine has been demonstrated,
      but learning curves and the high costs associated with this technology have
      limited its widespread use. Nonetheless, increased procedural speed, accuracy,
      and reduced exposure to radiation and contrast agent in robotically assisted
      catheter-based interventions, as well as reduced surgical trauma and shortened
      patient recovery times after robotic cardiovascular surgery are promising
      achievements in the field. 

PMID- 24663090
TI  - Prenatal screening for structural congenital heart disease.
AB  - Congenital heart defects can be diagnosed during fetal life using
      echocardiography. Prenatal diagnosis allows full investigation of affected
      fetuses for coexisting abnormalities, and gives time for parents to be informed
      about the prognosis of the fetus and treatments that might be required. In a
      minority of cases, where the natural history suggests an unfavourable outcome,
      prenatal diagnosis provides an opportunity for fetal cardiac intervention. For
      some cardiac lesions, notably hypoplastic left heart syndrome, transposition of
      the great arteries, and coarctation of the aorta, prenatal diagnosis has been
      shown to reduce postnatal morbidity and mortality. Some costs of care, notably
      the transport of critically ill infants, are reduced by prenatal diagnosis.
      Prenatal screening programmes typically recommend detailed assessment of fetuses
      judged to be at high risk of congenital heart disease. However, most cases of
      congenital heart disease arise in the low-risk population, and detection of
      affected fetuses in this setting depends on recognizing abnormalities of the
      heart during the midtrimester scan. Evidence supports the use of structured
      training interventions and feedback to those undertaking sonographic
      examinations, to improve the prenatal detection of congenital heart disease.

PMID- 24663091
TI  - The inflammatory response in myocardial injury, repair, and remodelling.
AB  - Myocardial infarction triggers an intense inflammatory response that is essential
      for cardiac repair, but which is also implicated in the pathogenesis of
      postinfarction remodelling and heart failure. Signals in the infarcted myocardium
      activate toll-like receptor signalling, while complement activation and
      generation of reactive oxygen species induce cytokine and chemokine upregulation.
      Leukocytes recruited to the infarcted area, remove dead cells and matrix debris
      by phagocytosis, while preparing the area for scar formation. Timely repression
      of the inflammatory response is critical for effective healing, and is followed
      by activation of myofibroblasts that secrete matrix proteins in the infarcted
      area. Members of the transforming growth factor beta family are critically
      involved in suppression of inflammation and activation of a profibrotic
      programme. Translation of these concepts to the clinic requires an understanding
      of the pathophysiological complexity and heterogeneity of postinfarction
      remodelling in patients with myocardial infarction. Individuals with an
      overactive and prolonged postinfarction inflammatory response might exhibit left
      ventricular dilatation and systolic dysfunction and might benefit from targeted
      anti-IL-1 or anti-chemokine therapies, whereas patients with an exaggerated
      fibrogenic reaction can develop heart failure with preserved ejection fraction
      and might require inhibition of the Smad3 (mothers against decapentaplegic
      homolog 3) cascade. Biomarker-based approaches are needed to identify patients
      with distinct pathophysiologic responses and to rationally implement inflammation
      modulating strategies. 

PMID- 24663093
TI  - MOGE(S) nosology in low-to-middle-income countries.

PMID- 24663092
TI  - Epidemiological studies of CHD and the evolution of preventive cardiology.
AB  - Cardiovascular diseases (CVDs) cause nearly one-third of all deaths worldwide.
      Coronary heart disease (CHD) accounts for the greatest proportion of CVDs, and
      risk factors such as hypertension, cigarette smoking, diabetes mellitus or
      elevated glucose level, elevated cholesterol levels, and obesity or being
      overweight are the top six causes of death globally. Ecological and population
      based longitudinal studies, conducted globally or within individual countries,
      have established the role of traditional and novel risk factors and measures of
      subclinical disease in the prediction of CHD. Risk assessment with short-term or
      long-term risk prediction algorithms can help to identify individuals who would
      benefit most from risk-factor interventions. Evaluation of novel risk factors and
      screening for subclinical atherosclerosis can also help to identify individuals
      at highest cardiovascular risk. Prevention of CHD focuses on identifying and
      managing risk factors at both the population and individual levels through
      primordial, primary, and secondary prevention. Epidemiological studies have
      provided the hypotheses for subsequent clinical trials that have documented the
      efficacy of risk-factor interventions, which are the basis of preventive
      cardiology. Future research efforts will determine the screening and intervention
      strategies that have the greatest effect on CHD prevention. 

PMID- 24663095
TI  - Television viewing over the life course and the metabolic syndrome in mid
      adulthood: a longitudinal population-based study.
AB  - BACKGROUND: Accumulating evidence suggests that television (TV) viewing is
      associated with cardio-metabolic risk, but little is known about how this
      relationship unfolds over the life course. This study employs a life course
      epidemiological framework by examining the potential cumulative effect of
      frequent TV viewing during adolescence and young adulthood on the prevalence of
      metabolic syndrome in mid-adulthood; and whether TV viewing during adolescence
      constitutes a sensitive period for the development of the metabolic syndrome in
      mid-adulthood. METHODS: We used data from the Northern Swedish Cohort, a
      nationally representative cohort comprising 855 participants (80% of the baseline
      sample). Data were collected during 1981-2008 and analysed in 2013. Logistic
      regression was applied to examine the associations between TV viewing at ages 16,
      21 and 30 years, and the metabolic syndrome at age 43 years. RESULTS: Cumulative
      frequent TV viewing was associated with subsequent prevalence of the metabolic
      syndrome after adjustment for potential confounders (p for trend=0.026). Watching
      'several shows a day' compared with 'one show/week' or less at age 16 years was
      associated with the metabolic syndrome at age 43 years after adjustment for later
      exposure (TV viewing at ages 21 and 30 years) and potential confounders (OR 1.86,
      95% CI 1.06 to 3.27). CONCLUSIONS: The number of life periods of frequent TV
      viewing during adolescence and early adulthood influenced cardio-metabolic risk
      in mid-adulthood in a dose-dependent manner, corresponding to a cumulative risk
      life course model. Additionally, TV viewing in adolescence may constitute a
      sensitive period for the metabolic syndrome in mid-adulthood.

PMID- 24663094
TI  - Accuracy and confidence of visual short-term memory do not go hand-in-hand:
      behavioral and neural dissociations.
AB  - Currently influential models of working memory posit that memory content is
      highly accessible to conscious inspection. These models predict that
      metacognition of memory performance should go hand-in-hand with the accuracy of
      the underlying memory representation. To test this view, we investigated how
      visual information presented during the maintenance period affects VSTM accuracy
      and confidence. We used a delayed cue-target orientation discrimination task in
      which participants were asked to hold in memory a grating, and during the
      maintenance period a second memory cue could be presented. VSTM accuracy of the
      first memory cue was impaired when the orientation of the second memory cue was
      sufficiently different. However, participants' response confidence was reduced
      whenever the second memory cue was presented; thus VSTM accuracy and confidence
      were dissociated. In a second experiment, we applied transcranial direct current
      stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) to
      investigate the causal role of this region in VSTM metacognition. Relative to the
      sham condition, anodal tDCS induced a general reduction in confidence ratings but
      did not affect VSTM accuracy. Overall, these results indicate that our
      metacognition of memory performance is influenced by factors other than the
      accuracy of the underlying memory representation. 

PMID- 24663096
TI  - Effects of straw incorporation on soil organic matter and soil water-stable
      aggregates content in semiarid regions of Northwest China.
AB  - The soil degradation caused by conventional tillage in rain-fed areas of
      northwest China is known to reduce the water-use efficiency and crop yield
      because of reduced soil porosity and the decreased availability of soil water and
      nutrients. Thus, we investigated the effects of straw incorporation on soil
      aggregates with different straw incorporation rates in semiarid areas of southern
      Ningxia for a three-year period (2008-2010). Four treatments were tested: (i) no
      straw incorporation (CK); (ii) incorporation of maize straw at a low rate of 4
      500 kg ha-1 (L); (iii) incorporation of maize straw at a medium rate of 9000 kg
      ha-1 (M); (iv) incorporation of maize straw at a high rate of 13 500 kg ha-1 (H).
      The results in the final year of treatments (2010) showed that the mean soil
      organic carbon storage of the 0-60 cm soil layers were significantly (P<0.05)
      increased with H, M, and L, by 21.40%, 20.38% and 8.21% compared with CK,
      respectively. Straw incorporation increased >0.25 mm water-stable macroaggregates
      level, geometric mean diameter, mean weight diameter and the aggregate stability,
      which were ranked in order of increasing straw incorporation rates: H/M > L > CK.
      Straw incorporation significantly (P<0.05) reduced the fractal dimension in the 0
      40 cm soil layers compared with CK. Our results suggest that straw incorporation
      is an effective practice for improving the soil aggregate structure and
      stability. 

PMID- 24663097
TI  - Periodontal infection and cardiorespiratory fitness in younger adults: results
      from continuous national health and nutrition examination survey 1999-2004.
AB  - OBJECTIVE: Previous studies report associations between periodontal infection and
      cardiorespiratory fitness but no study has examined the association among younger
      adults. Our objective was to study the association between clinical measures of
      periodontal infection and cardiorespiratory fitness levels among a population
      based sample of younger adults. METHODS: The Continuous National Health and
      Nutrition Examination Survey 1999-2004 enrolled 2,863 participants (46% women)
      who received a partial-mouth periodontal examination and completed a submaximal
      treadmill test for the assessment of estimated VO2 max(eVO2 max ). Participants
      were mean+/-SD age 33+/-9 years (range = 20-49 years), 30% Hispanic, 48% White,
      19% Black, and 3% other. Mean eVO2 max (mL/kg/minute) as well as eVO2 max<=32
      mL/kg/minute (20th percentile) were regressed across quartiles of mean probing
      depth and mean attachment loss in multivariable linear and logistic regression
      models. RESULTS: After multivariable adjustment, mean eVO2 max levels+/-SE across
      quartiles of attachment loss were 39.72+/-0.37, 39.64+/-0.34, 39.59+/-0.36, and
      39.85+/-0.39 (P = 0.99). Mean eVO2 max+/-SE across quartiles of probing depth
      were 39.57+/-0.32, 39.78+/-0.38, 39.19+/-0.25, and 40.37+/-0.53 (P = 0.28).
      Similarly, multivariable adjusted mean eVO2 max values were similar between
      healthy participants vs. those with moderate/severe periodontitis: 39.70+/-0.21
      vs. 39.70+/-0.90 (P = 1.00). The odds ratio (OR) for low eVO2 max comparing
      highest vs. lowest quartile of attachment loss = 0.89[95% CI 0.64-1.24]. The OR
      for comparing highest vs. lowest probing depth quartile = 0.77[95% CI 0.51-1.15].
      CONCLUSION: Clinical measures of periodontal infection were not related to
      cardiorespiratory fitness in a sample of generally healthy younger adults.

PMID- 24663098
TI  - Association between sleep quality and C-reactive protein: results from national
      health and nutrition examination survey, 2005-2008.
AB  - OBJECTIVE: Our objective was to explore the association between poor sleep
      quality and hs_CRP in an adult U.S. population. METHODS: This study focused on
      9,317 participants in the National Health and Nutrition Examination Survey
      (NHANES) from 2005-2008 who were aged 20-85 years, completed a sleep disorder
      questionnaire, and had available information on serum hs_CRP. Sleep quality was
      classified into three categories (good, moderate, poor) based on the responses of
      participants to the NHANES sleep disorder questionnaire. High CRP was defined as
      hs-CRP >1 md/dL. Linear regression model was applied to investigate the
      association between poor sleep quality and log-transformed hs_CRP. And logistic
      regression model was fitted to evaluate the association between sleep quality and
      the risk of high CRP. RESULTS: Females were more likely to report poor sleep
      quality than males (26% vs. 19%, p<0.0001). Each sleep disorder was significantly
      associated with increased hs_CRP and correlative to other sleep disorders. In
      fully-adjusted linear regression model, poor sleep quality was significantly
      associated with elevated hs_CRP (log transformed) among the overall sample and in
      females only (beta = 0.10, se = 0.03, p<0.01 and beta = 0.13, se = 0.04, p<0.01,
      respectively). In fully-adjusted logistics regression model, poor sleep quality
      was linked with risk of high CRP(OR: 1.42, 95%CI: 1.15-1.76 in overall sample and
      OR: 1.59, 95%CI: 1.18-2.14 in females, respectively). CONCLUSION: We found that
      poor sleep quality was independently associated with elevated hs_CRP in females
      but not in males in a U.S. adult population.

PMID- 24663099
TI  - Generalised power graph compression reveals dominant relationship patterns in
      complex networks.
AB  - We introduce a framework for the discovery of dominant relationship patterns in
      complex networks, by compressing the networks into power graphs with overlapping
      power nodes. When paired with enrichment analysis of node classification terms,
      the most compressible sets of edges provide a highly informative sketch of the
      dominant relationship patterns that define the network. In addition, this
      procedure also gives rise to a novel, link-based definition of overlapping node
      communities in which nodes are defined by their relationships with sets of other
      nodes, rather than through connections within the community. We show that this
      completely general approach can be applied to undirected, directed, and bipartite
      networks, yielding valuable insights into the large-scale structure of real-world
      networks, including social networks and food webs. Our approach therefore
      provides a novel way in which network architecture can be studied, defined and
      classified. 

PMID- 24663100
TI  - Modeling the zebrafish segmentation clock's gene regulatory network constrained
      by expression data suggests evolutionary transitions between oscillating and
      nonoscillating transcription.
AB  - During segmentation of vertebrate embryos, somites form in accordance with a
      periodic pattern established by the segmentation clock. In the zebrafish (Danio
      rerio), the segmentation clock includes six hairy/enhancer of split-related
      (her/hes) genes, five of which oscillate due to negative autofeedback. The
      nonoscillating gene hes6 forms the hub of a network of 10 Her/Hes protein dimers,
      which includes 7 DNA-binding dimers and 4 weak or non-DNA-binding dimers. The
      balance of dimer species is critical for segmentation clock function, and loss-of
      function studies suggest that the her genes have both unique and redundant
      functions within the clock. However, the precise regulatory interactions
      underlying the negative feedback loop are unknown. Here, we combine quantitative
      experimental data, in silico modeling, and a global optimization algorithm to
      identify a gene regulatory network (GRN) designed to fit measured transcriptional
      responses to gene knockdown. Surprisingly, we find that hes6, the clock gene that
      does not oscillate, responds to negative feedback. Consistent with prior in
      silico analyses, we find that variation in transcription, translation, and
      degradation rates can mediate the gain and loss of oscillatory behavior for genes
      regulated by negative feedback. Extending our study, we found that transcription
      of the nonoscillating Fgf pathway gene sef responds to her/hes perturbation
      similarly to oscillating her genes. These observations suggest a more extensive
      underlying regulatory similarity between the zebrafish segmentation clock and the
      mouse and chick segmentation clocks, which exhibit oscillations of her/hes genes
      as well as numerous other Notch, Fgf, and Wnt pathway genes. 

PMID- 24663101
TI  - Gene expression analysis of a panel of cell lines that differentially restrict
      HIV-1 CA mutants infection in a cyclophilin a-dependent manner.
AB  - HIV-1 replication is dependent on binding of the viral capsid to the host protein
      cyclophilin A (CypA). Interference with cyclophilin A binding, either by
      mutations in the HIV-1 capsid protein (CA) or by the drug cyclosporine A (CsA),
      inhibits HIV-1 replication in cell culture. Resistance to CsA is conferred by
      A92E or G94D substitutions in CA. The mutant viruses are also dependent on CsA
      for their replication. Interestingly, infection of some cell lines by these
      mutants is enhanced by CsA, while infection of others is not affected by the
      drug. The cells are thus termed nonpermissive and permissive, respectively, for
      infection by CsA-dependent mutants. The mechanistic basis for the cell type
      dependence is not well understood, but has been hypothesized to result from a
      dominant-acting host factor that blocks HIV-1 infection by a mechanism that
      requires CypA binding to the viral capsid. In an effort to identify a CypA
      dependent host restriction factor, we adopted a strategy involving comparative
      gene expression analysis in three permissive and three non-permissive cell types.
      We ranked the genes based on their relative overexpression in non-permissive cell
      types compared to the permissive cell types. Based on specific selection
      criteria, 26 candidate genes were selected and targeted using siRNA in
      nonpermissive (HeLa) cells. Depletion of none of the selected candidate genes led
      to the reversal of CsA-dependent phenotype of the A92E mutant. Our data suggest
      that none of the 26 genes tested is responsible for the dependence of the A92E
      mutant on CsA. Our study provides gene expression data that may be useful for
      future efforts to identify the putative CypA-dependent HIV-1 restriction factor
      and in studies of other cell-specific phenotypes. 

PMID- 24663102
TI  - Spectroscopic investigation of interaction between bovine serum albumin and amine
      functionalized silicon quantum dots.
AB  - We have investigated the dynamics and mechanistic details of the interaction
      between bovine serum albumin (BSA) and allylamine-capped silicon quantum dots (Si
      QDs) by means of fluorescence spectroscopy, circular dichroism (CD), and FTIR
      spectroscopy. The intrinsic fluorescence of BSA gets quenched in the presence of
      Si QDs due to ground-state complex formation. The binding stoichiometry and
      various thermodynamic parameters have been evaluated by using the van't Hoff
      equation. It has been observed that the association process is driven by a
      favourable negative enthalpy change with an unfavorable negative entropy change.
      These results have been explained by considering specific hydrogen bonding
      interactions between amine moieties (-NH2) of Si QDs and carboxylate groups (
      COO(-)) of aspartate (Asp) and glutamate (Glu) residues of BSA. Circular
      dichroism (CD) and FTIR spectroscopy revealed nominal changes in the secondary
      structure of the adsorbed proteins due to partial unfolding of the native protein
      upon surface adsorption while the overall tertiary structure remains close to
      that of the native state. 

PMID- 24663104
TI  - Improving the accuracy of whole genome prediction for complex traits using the
      results of genome wide association studies.
AB  - Utilizing the whole genomic variation of complex traits to predict the yet-to-be
      observed phenotypes or unobserved genetic values via whole genome prediction
      (WGP) and to infer the underlying genetic architecture via genome wide
      association study (GWAS) is an interesting and fast developing area in the
      context of human disease studies as well as in animal and plant breeding. Though
      thousands of significant loci for several species were detected via GWAS in the
      past decade, they were not used directly to improve WGP due to lack of proper
      models. Here, we propose a generalized way of building trait-specific genomic
      relationship matrices which can exploit GWAS results in WGP via a best linear
      unbiased prediction (BLUP) model for which we suggest the name BLUP|GA. Results
      from two illustrative examples show that using already existing GWAS results from
      public databases in BLUP|GA improved the accuracy of WGP for two out of the three
      model traits in a dairy cattle data set, and for nine out of the 11 traits in a
      rice diversity data set, compared to the reference methods GBLUP and BayesB.
      While BLUP|GA outperforms BayesB, its required computing time is comparable to
      GBLUP. Further simulation results suggest that accounting for publicly available
      GWAS results is potentially more useful for WGP utilizing smaller data sets
      and/or traits of low heritability, depending on the genetic architecture of the
      trait under consideration. To our knowledge, this is the first study
      incorporating public GWAS results formally into the standard GBLUP model and we
      think that the BLUP|GA approach deserves further investigations in animal
      breeding, plant breeding as well as human genetics. 

PMID- 24663105
TI  - Contraception and pregnancy counselling in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: The purpose of this study is to encourage discussion of
      reproduction issues in all patients of fertile age in order to prevent unplanned
      and ill-timed pregnancies in patients with rheumatoid arthritis (RA). RECENT
      FINDINGS: Counselling patients who desire children requires consideration of
      relevant reproductive health issues, including fertility, interaction of
      pregnancy and RA, and management during pregnancy and lactation. RA patients have
      no disease-related restrictions in regard to contraception, but need to be
      counselled on safe birth control particularly during treatment with potentially
      teratogenic drugs. In spite of mostly beneficial effects of pregnancy on RA,
      active disease and aggressive drug treatment can impair pregnancy outcomes.
      Options for drug therapy, though limited, may help to maintain low disease
      activity during pregnancy and lactation. SUMMARY: Careful preconception
      counselling and risk assessment is important in RA women, with a particular focus
      on preventing unplanned pregnancy by information on contraception. Antibody
      status and all medications need to be reviewed before pregnancy. Maintaining low
      disease activity before and during pregnancy is crucial for good outcomes.
      Preconceptional counselling shared with all health professionals engaged in the
      care of a patient helps to ensure healthy pregnancy outcomes for mother and
      child.

PMID- 24663106
TI  - Non-steroidal anti inflammatory drugs, glucocorticoids and disease modifying anti
      rheumatic drugs for the management of rheumatoid arthritis before and during
      pregnancy.
AB  - PURPOSE OF REVIEW: To review the recent literature on the safety of nonsteroidal
      anti-inflammatory drugs (NSAIDs), glucocorticoids and traditional disease
      modifying antirheumatic drugs before and during pregnancy. RECENT FINDINGS:
      Recent data suggest that the risk of cleft palate formation after in-utero
      glucocorticoid exposure is lower than previously reported. Two studies of
      inadvertent leflunomide exposure during early pregnancy suggest that this
      medication may be less teratogenic than previously thought. SUMMARY: Although
      NSAIDs are well tolerated for use during the first two trimesters of pregnancy,
      they should be avoided during a conception cycle so as not to impede
      implantation. After gestational week 30, these medications should be discontinued
      as they may cause premature closure of the ductus arteriosus. The nonfluorinated
      glucocorticoids, prednisone and prednisolone, can be used throughout pregnancy,
      although use during the first trimester may increase the risk of cleft palate
      formation. Protracted glucocorticoids exposure during pregnancy can cause
      maternal preterm premature rupture of the membranes, gestational hypertension and
      gestational diabetes. Methotrexate and leflunomide are teratogenic and should be
      avoided during pregnancy. The immunosuppressive agents, azathioprine, 6
      mercaptopurine and cyclosporine A, are compatible with pregnancy.

PMID- 24663107
TI  - Rheumatoid arthritis and pregnancy: impediments to optimal management of both
      biologic use before, during and after pregnancy.
AB  - PURPOSE OF REVIEW: Tumour necrosis factor inhibitors (TNFi) and other biologic
      response modifiers are being increasingly used for the treatment of rheumatoid
      arthritis (RA) among women of childbearing age, raising concerns regarding the
      potential safety of inadvertent or intentional exposure of these agents to the
      developing fetus. RECENT FINDINGS: TNFi and other biologics whose constructs
      contain a functional IgGFc piece are actively transported across the placenta
      during the second and third trimesters of pregnancy. Very little drug passively
      diffuses to the fetal circulation during the first trimester, when organogenesis
      occurs. Cumulative data from both the rheumatology and gastroenterology
      literature suggest that the rate of birth defects following antenatal TNFi
      exposure does not appear to be higher than that seen in the general population.
      There are very little data available on pregnancy outcomes following antenatal
      exposure to other biologic medications for RA. SUMMARY: Cumulative evidence
      suggests that TNFi use during pregnancy carries low risk for teratogenicity. A
      single case of fatal BCG infection in an exposed neonate following live virus
      vaccination highlights the potential need to defer live virus vaccines for at
      least 6 months in exposed neonates until more data of risk factors for infection
      susceptibility are available.

PMID- 24663108
TI  - Fertility and infertility in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: Despite decades of evidence suggesting that women with
      rheumatoid arthritis (RA) have fewer children than their healthy peers, this
      information is not widely known among clinicians. The causes of decreased
      fertility in this population have been largely unexplored, but likely revolve
      around altered inflammation, increased age when conception is attempted, limited
      sexual function, and possibly medications limiting ovarian function. RECENT
      FINDINGS: Several large Scandinavian cohorts and a cohort study in the United
      States demonstrate that women with RA have smaller families and are slower to
      conceive compared with other women. Personal choice to limit family size plays
      some role, as does infertility. Sexual function in women with RA is hampered by
      pain and fatigue, perhaps decreasing the opportunity for conception. Finally,
      data about the role of NSAIDs in preventing ovulation suggest that continued use
      of these medications may hinder conception. SUMMARY: Infertility in women with RA
      is an under-recognized, but remarkably common phenomenon. Although research
      continues into the underlying causes, physicians can discuss this topic and refer
      women to reproductive endocrinology when needed, thereby helping patients to
      build the families that they desire.

PMID- 24663109
TI  - Condensation of two-dimensional oxide-interfacial charges into one-dimensional
      electron chains by the misfit-dislocation strain field.
AB  - The success of semiconductor technology is largely ascribed to controlled impacts
      of strains and defects on the two-dimensional interfacial charges. Interfacial
      charges also appear in oxide heterojunctions such as LaAlO3/SrTiO3 and
      (Nd0.35Sr0.65)MnO3/SrTiO3. How the localized strain field of one-dimensional
      misfit dislocations, defects resulting from the intrinsic misfit strains, would
      affect the extended oxide-interfacial charges is intriguing and remains
      unresolved. Here we show the atomic-scale observation of one-dimensional electron
      chains formed in (Nd0.35Sr0.65)MnO3/SrTiO3 by the condensation of characteristic
      two-dimensional interfacial charges into the strain field of periodically arrayed
      misfit dislocations, using chemical mapping and quantification by scanning
      transmission electron microscopy. The strain-relaxed inter-dislocation regions
      are readily charge depleted, otherwise decorated by the pristine charges, and the
      corresponding total-energy calculations unravel the undocumented charge-reservoir
      role played by the dislocation-strain field. This two-dimensional-to-one
      dimensional electronic condensation represents a novel electronic-inhomogeneity
      mechanism at oxide interfaces and could stimulate further studies of one
      dimensional electron density in oxide heterostructures. 

PMID- 24663111
TI  - Two new antibiotic pyridones produced by a marine fungus, Trichoderma sp. strain
      MF106.
AB  - Two unusual pyridones, trichodin A (1) and trichodin B (2), together with the
      known compound, pyridoxatin (3), were extracted from mycelia and culture broth of
      the marine fungus, Trichoderma sp. strain MF106 isolated from the Greenland Seas.
      The structures of the new compounds were characterized as an intramolecular
      cyclization of a pyridine basic backbone with a phenyl group. The structure and
      relative configuration of the new compounds were established by spectroscopic
      means. The new compound 1 and the known compound 3 showed antibiotic activities
      against the clinically relevant microorganism, Staphylococcus epidermidis, with
      IC50 values of 24 MUM and 4 MUM, respectively.

PMID- 24663110
TI  - Domoic acid epileptic disease.
AB  - Domoic acid epileptic disease is characterized by spontaneous recurrent seizures
      weeks to months after domoic acid exposure. The potential for this disease was
      first recognized in a human case study of temporal lobe epilepsy after the 1987
      amnesic shellfish-poisoning event in Quebec, and was characterized as a chronic
      epileptic syndrome in California sea lions through investigation of a series of
      domoic acid poisoning cases between 1998 and 2006. The sea lion study provided a
      breadth of insight into clinical presentations, unusual behaviors, brain
      pathology, and epidemiology. A rat model that replicates key observations of the
      chronic epileptic syndrome in sea lions has been applied to identify the
      progression of the epileptic disease state, its relationship to behavioral
      manifestations, and to define the neural systems involved in these behavioral
      disorders. Here, we present the concept of domoic acid epileptic disease as a
      delayed manifestation of domoic acid poisoning and review the state of knowledge
      for this disease state in affected humans and sea lions. We discuss causative
      mechanisms and neural underpinnings of disease maturation revealed by the rat
      model to present the concept for olfactory origin of an epileptic disease;
      triggered in dendodendritic synapases of the olfactory bulb and maturing in the
      olfactory cortex. We conclude with updated information on populations at risk,
      medical diagnosis, treatment, and prognosis. 

PMID- 24663112
TI  - Dereplication strategies for targeted isolation of new antitrypanosomal
      actinosporins A and B from a marine sponge associated-Actinokineospora sp. EG49.
AB  - High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic
      resonance (NMR) spectroscopy were employed as complementary metabolomic tools to
      dereplicate the chemical profile of the new and antitrypanosomally active sponge
      associated bacterium Actinokineospora sp. EG49 extract. Principal Component
      (PCA), hierarchical clustering (HCA), and orthogonal partial least square
      discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of
      crude extracts from four different fermentation approaches. Statistical analysis
      identified the best culture one-strain-many-compounds (OSMAC) condition and
      extraction procedure, which was used for the isolation of novel bioactive
      metabolites. As a result, two new O-glycosylated angucyclines, named
      actinosporins A (1) and B (2), were isolated from the broth culture of
      Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge
      Spheciospongia vagabunda. The structures of actinosporins A and B were determined
      by 1D- and 2D-NMR techniques, as well as high resolution tandem mass
      spectrometry. Testing for antiparasitic properties showed that actinosporin A
      exhibited activity against Trypanosoma brucei brucei with an IC50 value of 15 uM;
      however no activity was detected against Leishmania major and Plasmodium
      falciparum, therefore suggesting its selectivity against the parasite Trypanosoma
      brucei brucei; the causative agent of sleeping sickness.

PMID- 24663113
TI  - Optimization of medium using response surface methodology for lipid production by
      Scenedesmus sp.
AB  - Lipid production is an important indicator for assessing microalgal species for
      biodiesel production. In this work, the effects of medium composition on lipid
      production by Scenedesmus sp. were investigated using the response surface
      methodology. The results of a Plackett-Burman design experiment revealed that
      NaHCO3, NaH2PO4.2H2O and NaNO3 were three factors significantly influencing lipid
      production, which were further optimized by a Box-Behnken design. The optimal
      medium was found to contain 3.07 g L-1 NaHCO3, 15.49 mg L-1 NaH2PO4.2H2O and
      803.21 mg L-1 NaNO3. Using the optimal conditions previously determined, the
      lipid production (304.02 mg.L-1) increased 54.64% more than that using the
      initial medium, which agreed well with the predicted value 309.50 mg L-1.
      Additionally, lipid analysis found that palmitic acid (C16:0) and oleic acid
      (C18:1) dominantly constituted the algal fatty acids (about 60% of the total
      fatty acids) and a much higher content of neutral lipid accounted for 82.32% of
      total lipids, which strongly proved that Scenedesmus sp. is a very promising
      feedstock for biodiesel production.

PMID- 24663114
TI  - A novel lipid extraction method from wet microalga Picochlorum sp. at room
      temperature.
AB  - A novel method using ethanol was proposed for extracting lipids from wet
      microalga Picochlorum sp. at room temperature and pressure. In this study,
      Central Composite design (CCD) was applied to investigate the optimum conditions
      of lipid extraction. The results revealed that the solvent to biomass ratio had
      the largest effect on lipid extraction efficiency, followed by extraction time
      and temperature. A high lipid extraction yield (33.04% of the dry weight) was
      obtained under the following extraction conditions: 5 mL solvents per gram of wet
      biomass for 37 min with gentle stirring at room temperature. The extraction yield
      was comparable to that obtained by the widely used Bligh-Dyer method.
      Furthermore, no significant differences in the distribution of lipid classes and
      fatty acid composition were observed according to different extraction methods.
      In conclusion, these results indicated that the proposed procedure using ethanol
      could extract lipids from wet biomass efficiently and had giant potential for
      lipid extraction at large scale. 

PMID- 24663115
TI  - Spirobisnaphthalenes from the mangrove-derived fungus Rhytidhysteron sp. AS21B.
AB  - Three new spirobisnaphthalenes (1-3) were isolated from the mangrove-derived
      fungus Rhytidhysteron sp., together with five known derivatives (4-8). The
      structures of the compounds were established on the basis of extensive
      spectroscopic data, and the relative configurations of their stereogenic carbons
      were determined by a single-crystal X-ray crystallographic analysis. Compounds 3
      5 displayed cytotoxicity against both cancer cell lines, MCF-7 and CaSki, while 2
      was active only on CaSKi cells. 

PMID- 24663116
TI  - Phylogenetic diversity and biological activity of actinobacteria isolated from
      the Chukchi Shelf marine sediments in the Arctic Ocean.
AB  - Marine environments are a rich source of Actinobacteria and have the potential to
      produce a wide variety of biologically active secondary metabolites. In this
      study, we used four selective isolation media to culture Actinobacteria from the
      sediments collected from the Chukchi Shelf in the Arctic Ocean. A total of 73
      actinobacterial strains were isolated. Based on repetitive DNA fingerprinting
      analysis, we selected 30 representatives for partial characterization according
      to their phylogenetic diversity, antimicrobial activities and secondary
      metabolite biosynthesis genes. Results from the 16S rRNA gene sequence analysis
      indicated that the 30 strains could be sorted into 18 phylotypes belonging to 14
      different genera: Agrococcus, Arsenicicoccus, Arthrobacter, Brevibacterium,
      Citricoccus, Janibacter, Kocuria, Microbacterium, Microlunatus, Nocardioides,
      Nocardiopsis, Saccharopolyspora, Salinibacterium and Streptomyces. To our
      knowledge, this paper is the first report on the isolation of Microlunatus genus
      members from marine habitats. Of the 30 isolates, 11 strains exhibited
      antibacterial and/or antifungal activity, seven of which have activities against
      Bacillus subtilis and Candida albicans. All 30 strains have at least two
      biosynthetic genes, one-third of which possess more than four biosynthetic genes.
      This study demonstrates the significant diversity of Actinobacteria in the
      Chukchi Shelf sediment and their potential for producing biologically active
      compounds and novel material for genetic manipulation or combinatorial
      biosynthesis. 

PMID- 24663117
TI  - The challenge of ecophysiological biodiversity for biotechnological applications
      of marine microalgae.
AB  - In this review, we aim to explore the potential of microalgal biodiversity and
      ecology for biotechnological use. A deeper exploration of the biodiversity
      richness and ecophysiological properties of microalgae is crucial for enhancing
      their use for applicative purposes. After describing the actual biotechnological
      use of microalgae, we consider the multiple faces of taxonomical, morphological,
      functional and ecophysiological biodiversity of these organisms, and investigate
      how these properties could better serve the biotechnological field. Lastly, we
      propose new approaches to enhancing microalgal growth, photosynthesis, and
      synthesis of valuable products used in biotechnological fields, mainly focusing
      on culture conditions, especially light manipulations and genetic modifications. 

PMID- 24663118
TI  - Antioxidant and antimicrobial potential of the Bifurcaria bifurcata epiphytic
      bacteria.
AB  - Surface-associated marine bacteria are an interesting source of new secondary
      metabolites. The aim of this study was the isolation and identification of
      epiphytic bacteria from the marine brown alga, Bifurcaria bifurcata, and the
      evaluation of the antioxidant and antimicrobial activity of bacteria extracts.
      The identification of epiphytic bacteria was determined by 16S rRNA gene
      sequencing. Bacteria extracts were obtained with methanol and dichloromethane
      (1:1) extraction. The antioxidant activity of extracts was performed by
      quantification of total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging activity and oxygen radical absorbance capacity (ORAC).
      Antimicrobial activities were evaluated against Escherichia coli, Pseudomonas
      aeruginosa, Bacillus subtilis, Salmonella enteritidis, Staphylococcus aureus,
      Saccharomyces cerevisiae and Candida albicans. A total of 39 Bifurcaria bifurcata
      associated bacteria were isolated and 33 were identified as Vibrio sp. (48.72%),
      Alteromonas sp. (12.82%), Shewanella sp. (12.26%), Serratia sp. (2.56%),
      Citricoccus sp. (2.56%), Cellulophaga sp. (2.56%), Ruegeria sp. (2.56%) and
      Staphylococcus sp. (2.56%). Six (15.38%) of the 39 bacteria Bifurcaria bifurcata
      associated bacteria presented less than a 90% Basic Local Alignment Search Tool
      (BLAST) match, and some of those could be new. The highest antioxidant activity
      and antimicrobial activity (against B. subtilis) was exhibited by strain 16
      (Shewanella sp.). Several strains also presented high antimicrobial activity
      against S. aureus, mainly belonging to Alteromonas sp. and Vibrio sp. There were
      no positive results against fungi and Gram-negative bacteria. Bifurcaria
      bifurcata epiphytic bacteria were revealed to be excellent sources of natural
      antioxidant and antimicrobial compounds. 

PMID- 24663119
TI  - New and rare carotenoids isolated from marine bacteria and their antioxidant
      activities.
AB  - Marine bacteria have not been examined as extensively as land bacteria. We
      screened carotenoids from orange or red pigments-producing marine bacteria
      belonging to rare or novel species. The new acyclic carotenoids with a C30
      aglycone, diapolycopenedioc acid xylosylesters A-C and methyl 5-glucosyl-5,6
      dihydro-apo-4,4'-lycopenoate, were isolated from the novel Gram-negative
      bacterium Rubritalea squalenifaciens, which belongs to phylum Verrucomicrobia, as
      well as the low-GC Gram-positive bacterium Planococcus maritimus strain iso-3
      belonging to the class Bacilli, phylum Firmicutes, respectively. The rare
      monocyclic C40 carotenoids, (3R)-saproxanthin and (3R,2'S)-myxol, were isolated
      from novel species of Gram-negative bacteria belonging to the family
      Flavobacteriaceae, phylum Bacteroidetes. In this review, we report the structures
      and antioxidant activities of these carotenoids, and consider relationships
      between bacterial phyla and carotenoid structures.

PMID- 24663121
TI  - Simulation of diffusion in a crowded environment.
AB  - We performed extensive and systematic simulation studies of two-dimensional fluid
      motion in a complex crowded environment. In contrast to other studies we focused
      on cooperative phenomena that occurred if the motion of particles takes place in
      a dense crowded system, which can be considered as a crude model of a cellular
      membrane. Our main goal was to answer the following question: how do the fluid
      molecules move in an environment with a complex structure, taking into account
      the fact that motions of fluid molecules are highly correlated. The dynamic
      lattice liquid (DLL) model, which can work at the highest fluid density, was
      employed. Within the frame of the DLL model we considered cooperative motion of
      fluid particles in an environment that contained static obstacles. The dynamic
      properties of the system as a function of the concentration of obstacles were
      studied. The subdiffusive motion of particles was found in the crowded system.
      The influence of hydrodynamics on the motion was investigated via analysis of the
      displacement in closed cooperative loops. The simulation and the analysis
      emphasize the influence of the movement correlation between moving particles and
      obstacles. 

PMID- 24663120
TI  - Different frequencies of drug resistance mutations among HIV-1 subtypes
      circulating in China: a comprehensive study.
AB  - The rapid spreading of HIV drug resistance is threatening the overall success of
      free HAART in China. Much work has been done on drug-resistant mutations,
      however, most of which were based on subtype B. Due to different genetic
      background, subtypes difference would have an effect on the development of drug
      resistant mutations, which has already been proved by more and more studies. In
      China, the main epidemic subtypes are CRF07_BC, CRF08_BC, Thai B and CRF01_AE.
      The depiction of drug resistance mutations in those subtypes will be helpful for
      the selection of regimens for Chinese. In this study, the distributions
      difference of amino acids at sites related to HIV drug resistance were compared
      among subtype B, CRF01_AE, CRF07_BC and CRF08_BC strains prevalent in China. The
      amino acid composition of sequences belonging to different subtypes, which were
      obtained from untreated and treated individuals separately, were also compared.
      The amino acids proportions of 19 sites in RT among subtype B, CRF01_AE and
      CRF08_BC have significant difference in drug resistance groups (chi-square test,
      p<0.05). Genetic barriers analysis revealed that sites 69, 138, 181, 215 and 238
      were significantly different among subtypes (Kruskal Wallis test, p<0.05). All
      subtypes shared three highest prevalent drug resistance sites 103, 181 and 184 in
      common. Many drug resistant sites in protease show surprising high proportions in
      almost all subtypes in drug-naive patients. This is the first comprehensive study
      in China on different development of drug resistance among different subtypes.
      The detailed data will lay a foundation for HIV treatment regimens design and
      improve HIV therapy in China. 

PMID- 24663122
TI  - Excess burden of depression among HIV-infected persons receiving medical care in
      the united states: data from the medical monitoring project and the behavioral
      risk factor surveillance system.
AB  - BACKGROUND: With increased life expectancy for HIV-infected persons, there is
      concern regarding comorbid depression because of its common occurrence and
      association with behaviors that may facilitate HIV transmission. Our objectives
      were to estimate the prevalence of current depression among HIV-infected persons
      receiving care and assess the burden of major depression, relative to that in the
      general population. METHODS AND FINDINGS: We used data from the Medical
      Monitoring Project (MMP) and the Behavioral Risk Factors Surveillance System
      (BRFSS). The eight-item Patient Health Questionnaire was used to identify
      depression. To assess the burden of major depression among HIV-infected persons
      receiving care, we compared the prevalence of current major depression between
      the MMP and BRFSS populations using stratified analyses that simultaneously
      controlled for gender and, in turn, each of the potentially confounding
      demographic factors of age, race/ethnicity, education, and income. Each
      unadjusted comparison was summarized as a prevalence ratio (PR), and each of the
      adjusted comparisons was summarized as a standardized prevalence ratio (SPR).
      Among HIV-infected persons receiving care, the prevalence of a current episode of
      major depression and other depression, respectively, was 12.4% (95% CI: 11.2,
      13.7) and 13.2% (95% CI: 12.0%, 14.4%). Overall, the PR comparing the prevalence
      of current major depression between HIV-infected persons receiving care and the
      general population was 3.1. When controlling for gender and each of the factors
      age, race/ethnicity, and education, the SPR (3.3, 3.0, and 2.9, respectively) was
      similar to the PR. However, when controlling for gender and annual household
      income, the SPR decreased to 1.5. CONCLUSIONS: Depression remains a common
      comorbidity among HIV-infected persons. The overall excess burden among HIV
      infected persons receiving care is about three-times that among the general
      population and is associated with differences in annual household income between
      the two populations. Relevant efforts are needed to reduce this burden.

PMID- 24663123
TI  - Human cancer cells retain modest levels of enzymatically active matriptase only
      in extracellular milieu following induction of zymogen activation.
AB  - The type 2 transmembrane serine protease matriptase is broadly expressed in human
      carcinomas and hematological cancers. The proteolytic activity of matriptase is a
      potential target of drugs and imaging probes. We assessed the fate of active
      matriptase following the induction of matriptase zymogen activation. Exposing
      eight human carcinoma cells to pH 6.0 buffer induced robust matriptase zymogen
      activation followed by rapid inhibition of the nascent active matriptase by
      hepatocyte growth factor activator inhibitor (HAI)-1. Consequently, no
      enzymatically active matriptase was detected in these cells. Some active
      matriptase is, however, rapidly shed to the extracellular milieu by these
      carcinoma cells. The lack of cell-associated active matriptase and the shedding
      of active matriptase were also observed in two hematological cancer lines.
      Matriptase shedding is correlated closely with the induction of matriptase
      activation, suggesting that matriptase activation and shedding are kinetically
      coupled. The coupling allows a proportion of active matriptase to survive HAI-1
      inhibition by rapid shedding from cell surface. Our study suggests that cellular
      free, active matriptase is scarce and might not be an effective target for in
      vivo imaging and drug development. 

PMID- 24663125
TI  - Imaging: Lighting up tumours.

PMID- 24663124
TI  - Prostaglandin (PG) F2 alpha synthesis in human subcutaneous and omental adipose
      tissue: modulation by inflammatory cytokines and role of the human aldose
      reductase AKR1B1.
AB  - INTRODUCTION: PGF2alpha may be involved in the regulation of adipose tissue
      function. OBJECTIVES: 1) To examine PGF2alpha release by primary preadipocytes,
      mature adipocytes and whole tissue explants from the subcutaneous and omental fat
      compartments; 2) To assess which PGF synthase is the most relevant in human
      adipose tissue. METHODS: Fat samples were obtained by surgery in women. PGF2alpha
      release by preadipocytes, adipocytes and explants under stimulation by TNF-alpha,
      IL-1beta or both was measured. Messenger RNA expression levels of AKR1B1 and
      AKR1C3 were measured by RT-PCR in whole adipose tissue and cytokine-treated
      preadipocytes. The effect of AKR1B1 inhibitor ponalrestat on PGF2alpha synthesis
      was investigated. RESULTS: PGF2alpha release was significantly induced in
      response to cytokines compared to control in omental (p = 0.01) and to a lesser
      extent in subcutaneous preadipocytes (p = 0.02). Messenger RNA of COX-2 was
      significantly higher in omental compared to subcutaneous preadipocytes in
      response to combined TNF-alpha and IL-1beta (p = 0.01). Inflammatory cytokines
      increased AKR1B1 mRNA expression and protein levels (p<=0.05), but failed to
      increase expression levels of AKR1C3 in cultured preadipocytes. Accordingly,
      ponalrestat blunted PGF2alpha synthesis by preadipocytes in basal and stimulated
      conditions (p<=0.05). Women with the highest PGF2alpha release by omental
      adipocytes had a higher BMI (p = 0.05), waist circumference (p<=0.05) and HOMAir
      index (p<=0.005) as well as higher mRNA expression of AKR1B1 in omental (p<0.10)
      and subcutaneous (p<=0.05) adipose tissue compared to women with low omental
      adipocytes PGF2alpha release. Positive correlations were observed between mRNA
      expression of AKR1B1 in both compartments and BMI, waist circumference as well as
      HOMAir index (p<=0.05 for all). CONCLUSION: PGF2alpha release by omental mature
      adipocytes is increased in abdominally obese women. Moreover, COX-2 expression
      and PGF2alpha release is particularly responsive to inflammatory stimulation in
      omental preadipocytes. Yet, blockade of PGF synthase AKR1B1 inhibits most of the
      PGF2alpha release.

PMID- 24663126
TI  - Surgery: Stereotactic radiosurgery--new options for multiple brain metastases?

PMID- 24663128
TI  - Computed tomography utilization in the North Carolina Medicaid population with a
      focus on "high exposure" patients, 2007-2012.
AB  - BACKGROUND: We examined trends in utilization of computed tomography (CT) among
      Medicaid enrollees in North Carolina, the clinical setting in which those CT
      scans were performed, and the number of enrollees known to have undergone 10 or
      more scans in a given year. METHODS: North Carolina Medicaid claims were analyzed
      to determine the number of CT studies performed between January 1, 2007, and
      December 31, 2012. We assessed the number of "high exposure" patients--those who
      received 10 or more CT scans in a given calendar year--and divided this group
      into patients with a diagnosis of cancer and patients without a diagnosis of
      cancer. We also determined the type of site at which each CT scan was performed.
      RESULTS: Over the 6-year period 2007-2012, the percentage of all enrollees who
      underwent any CT study ranged from 8.0% to 9.6% (126,082-177,425 enrollees). The
      number of CT scans performed annually increased from 2007 to 2009 and then
      plateaued. The number of high-exposure patients increased gradually, from 2,171
      in 2007 to 4,017 in 2012. The majority of CT scans of high--exposure patients-
      150,241 of 251,052 (59.8%)--were performed in non office outpatient settings,
      such as emergency departments or urgent care centers. CONCLUSION: Although the
      number of CT scans performed annually in the North Carolina Medicaid population
      stabilized in the late 2000s (as did CT use nationally), the percentage of high
      exposure patients has continued to rise. Physicians and patients need to be
      further educated in order to promote radiation safety and to decrease unnecessary
      radiation exposure.

PMID- 24663129
TI  - With "big data" comes big responsibility: outreach to North Carolina Medicaid
      patients with 10 or more computed tomography scans in 12 months.
AB  - BACKGROUND: Patients are being exposed to increasing levels of ionizing
      radiation, much of it from computed tomography (CT) scans. METHODS: Adults
      without a cancer diagnosis who received 10 or more CT scans in 2010 were
      identified from North Carolina Medicaid claims data and were sent a letter in
      July 2011 informing them of their radiation exposure; those who had undergone 20
      or more CT scans in 2010 were also telephoned. The CT scan exposure of these high
      exposure patients during the 12 months following these interventions was compared
      with that of adult Medicaid patients without cancer who had at least 1 CT scan
      but were not in the intervention population. RESULTS: The average number of CT
      scans per month for the high-exposure population decreased over time, but most of
      that reduction occurred 6-9 months before our interventions took place. At about
      the same time, the number of CT scans per month also decreased in adult Medicaid
      patients without cancer who had at least 1 CT scan but were not in the
      intervention population. LIMITATIONS: Our data do not include information about
      CT scans that may have been performed during times when patients were not covered
      by Medicaid. Some of our letters may not have been received or understood. Some
      high-exposure patients were unintentionally excluded from our study because
      organization of data on Medicaid claims varies by setting of care. CONCLUSION:
      Our patient education intervention was not temporally associated with significant
      decreases in subsequent CT exposure. Effecting behavior change to reduce exposure
      to ionizing radiation requires more than an educational letter or telephone call.

PMID- 24663130
TI  - Revealing the mysteries of medicine.

PMID- 24663131
TI  - From Roentgen to magnetic resonance imaging: the history of medical imaging.
AB  - Medical imaging has advanced in remarkable ways since the discovery of x-rays 120
      years ago. Today's radiologists can image the human body in intricate detail
      using computed tomography, magnetic resonance imaging, positron emission
      tomography, ultrasound, and various other modalities. Such technology allows for
      improved screening, diagnosis, and monitoring of disease, but it also comes with
      risks. Many imaging modalities expose patients to ionizing radiation, which
      potentially increases their risk of developing cancer in the future, and imaging
      may also be associated with possible allergic reactions or risks related to the
      use of intravenous contrast agents. In addition, the financial costs of imaging
      are taxing our health care system, and incidental findings can trigger anxiety
      and further testing. This issue of the NCMJ addresses the pros and cons of
      medical imaging and discusses in detail the following uses of medical imaging:
      screening for breast cancer with mammography, screening for osteoporosis and
      monitoring of bone mineral density with dual-energy x-ray absorptiometry,
      screening for congenital hip dysplasia in infants with ultrasound, and evaluation
      of various heart conditions with cardiac imaging. Together, these articles show
      the challenges that must be met as we seek to harness the power of today's
      imaging technologies, as well as the potential benefits that can be achieved when
      these hurdles are overcome. 

PMID- 24663127
TI  - Determining the optimal dose in the development of anticancer agents.
AB  - Identification of the optimal dose remains a key challenge in drug development.
      For cytotoxic drugs, the standard approach is based on identifying the maximum
      tolerated dose (MTD) in phase I trials and incorporating this to subsequent
      trials. However, this strategy does not take into account important aspects of
      clinical pharmacology. For targeted agents, the dose-effect relationships from
      preclinical studies are less obvious, and it is important to change the way these
      agents are developed to avoid recommending drug doses for different populations
      without evidence of differential antitumour effects in different diseases. The
      use of expanded cohorts in phase I trials to better define MTD and refine dose
      optimization should be further explored together with a focus on efficacy rather
      than toxicity-based predictions. Another key consideration in dose optimization
      is related to interindividual pharmacokinetic variability. High variability in
      intra-individual pharmacokinetics has been observed for many orally-administered
      drugs, especially those with low bioavailability, which might complicate
      identification of dose-effect relationships. End-organ dysfunction, interactions
      with other prescription drugs, herbal supplements, adherence, and food intake can
      influence pharmacokinetics. It is important these variables are identified during
      early clinical trials and considered in the development of further phase II and
      subsequent large-scale phase III studies. 

PMID- 24663133
TI  - Breast cancer screening.
AB  - Mammography remains the primary technique for breast cancer screening. Women with
      dense breast tissue may benefit from digital mammography and tomosynthesis, and
      women at high risk may benefit from magnetic resonance imaging. However, false
      positive results are problematic. The North Carolina breast density law
      necessitates education about screening options for women with dense breasts. 

PMID- 24663132
TI  - Patient engagement and informed decision making regarding medical imaging.
AB  - Misuse and overuse of medical imaging have gained widespread attention due to
      rising costs, radiation exposure risks, and limited comparative effectiveness
      evidence. Involving patients in shared decision making offers an opportunity to
      more clearly define risks and benefits, thus allowing patients to consider both
      personal values and the best available evidence. 

PMID- 24663134
TI  - The value of diagnostic medical imaging.
AB  - Diagnostic medical imaging has clear clinical utility, but it also imposes
      significant costs on the health care system. This commentary reviews the factors
      that drive the cost of medical imaging, discusses current interventions, and
      suggests possible future courses of action. 

PMID- 24663135
TI  - The health risks of ionizing radiation from computed tomography.
AB  - Concerns have increased about the potential health risks of ionizing radiation
      from computed tomography (CT) scans. This paper discusses the biological effects
      of radiation, describes research findings related to CT use, cites strategies for
      radiation dose reduction, and emphasizes the need to be judicious in ordering CT
      scans for children. 

PMID- 24663136
TI  - Overuse of computed tomography and the onslaught of incidental findings.

PMID- 24663137
TI  - Ultrasound as an alternative to computed tomography for pediatric imaging.

PMID- 24663138
TI  - Dual-energy x-ray absorptiometry: overused, neglected, or just misunderstood?
AB  - Assessment of bone mineral density (BMD) by dual-energy x-ray absorptiometry
      (DXA) plays a vital role in the diagnosis of osteoporosis and in monitoring a
      patient's response to drug therapy. This commentary will discuss controversies
      surrounding the use of DXA for screening and monitoring of BMD in women. 

PMID- 24663139
TI  - Patient requests for office-based imaging.
AB  - The rising cost of health care affects our economy and can impact the health of
      our citizens. Costs can be divided into direct costs, which are incurred in the
      provision of services and procedures, and ancillary costs, such as labs and
      imaging. While ancillary services greatly assist providers in diagnosing and
      treating medical conditions, they can be overused or inappropriately used and can
      lead to adverse events. All providers should work to order the most appropriate
      imaging and tests and to protect patients at all times. 

PMID- 24663140
TI  - Keepsake prenatal ultrasound: pros and cons of non-medically indicated imaging.

PMID- 24663141
TI  - Ultrasound for screening and management of developmental dysplasia of the hip.
AB  - Developmental dysplasia of the hip (DDH) is a significant cause of disability in
      children and young adults. Early detection of this condition allows for
      nonoperative treatment, but the efficacy of DDH screening programs has not been
      clearly established. This article discusses the role of ultrasound in the
      diagnosis and management of DDH. 

PMID- 24663142
TI  - Noninvasive cardiovascular imaging.
AB  - Over the past 2 decades, use of noninvasive cardiovascular imaging has increased
      dramatically. This article provides a brief synopsis of the current state of
      several technologies-- echocardiography, cardiac magnetic resonance imaging, and
      cardiac computed tomography--as well as a glimpse at future possibilities in
      cardiac imaging. 

PMID- 24663143
TI  - The North Carolina Breast and Cervical Cancer Control Program.

PMID- 24663144
TI  - The Affordable Care Act: ethically right for our wealthy nation's health.

PMID- 24663145
TI  - On the mechanisms of the recurvature of super typhoon Megi.
AB  - Tropical cyclones (TC) are one of the most threatening natural hazards to human
      beings. Although significant improvements have been made in the track prediction
      of TCs during the past several decades, considerable uncertainties still exist,
      especially for recurving tracks. In this study, we explore the physical
      mechanisms that drove the large recurvature of super typhoon Megi through
      numerical sensitivity experiments using a regional atmospheric model. The results
      indicate that the cold air intrusion from the northwest to the southeast of China
      is the main cause of the sharp turning of Megi. This finding suggests that a cold
      air intrusion could be taken as an indicator for predicting the recurvature of a
      tropical cyclone in the future. 

PMID- 24663146
TI  - On the macromolecular cellulosic network of paper: changes induced by acid
      hydrolysis studied by NMR diffusometry and relaxometry.
AB  - The cellulosic network of artificially acidified paper has been studied by 2D NMR
      relaxometry, NMR diffusometry and NMR diffusion-diffraction. Results show that
      the acidifying treatment enlarges the macropore structure of paper increasing the
      pore connectivity and modifying the exchange between water populations localized
      in amorphous cellulose. Acidification damage suggests that simple breaking of the
      amorphous portion of fibrils occurs. Nevertheless, under a specific acidifying
      condition, a rearrangement in the cellulose network seems to take place, with a
      reduction of the average macropore size and a loss of pore connectivity. The
      identification of water populations by 2D relaxation maps allows for monitoring
      the changes in cellulose water mobility due to the depolymerization process. In
      general the relaxation and self-diffusion results confirm that water mobility
      increases with acidification. 

PMID- 24663147
TI  - Chemically robust fluoroalkyl phthalocyanine-oligonucleotide bioconjugates and
      their GRP78 oncogene photocleavage activity.
AB  - The first representative of functionalized fluoroalkyl phthalocyanines,
      F48H7(COOH)PcZn, is reported. The complex generates (1)O2 affording long-lasting
      photooxidation of an external substrate without self-decomposition. The
      carboxylic group couples with an antisense oligonucleotide targeting GRP78
      oncogenes, resulting in the F48H7PcZn-cancer targeting oligonucleotide (CTO). The
      bioconjugated fluorophthalocyanine effectively hybridizes complementary GRP78 DNA
      and mRNA sequences. Piperidine cleavage assays reveal desired photochemical
      oligonucleotide oxidative degradation for both F48H7PcZn-CTO:DNA and F48H7PcZn
      CTO:mRNA hybrids. This new materials strategy could be extended to other
      functional fluorinated phthalocyanines-antisense oligonucleotide combinations for
      long-lasting oncogene-targeting photodynamic therapy. 

PMID- 24663150
TI  - Synchronous precessional motion of multiple domain walls in a ferromagnetic
      nanowire by perpendicular field pulses.
AB  - Magnetic storage and logic devices based on magnetic domain wall motion rely on
      the precise and synchronous displacement of multiple domain walls. The
      conventional approach using magnetic fields does not allow for the synchronous
      motion of multiple domains. As an alternative method, synchronous current-induced
      domain wall motion was studied, but the required high-current densities prevent
      widespread use in devices. Here we demonstrate a radically different approach: we
      use out-of-plane magnetic field pulses to move in-plane domains, thus combining
      field-induced magnetization dynamics with the ability to move neighbouring domain
      walls in the same direction. Micromagnetic simulations suggest that synchronous
      permanent displacement of multiple magnetic walls can be achieved by using
      transverse domain walls with identical chirality combined with regular pinning
      sites and an asymmetric pulse. By performing scanning transmission X-ray
      microscopy, we are able to experimentally demonstrate in-plane magnetized domain
      wall motion due to out-of-plane magnetic field pulses. 

PMID- 24663153
TI  - Yielding and flow of solutions of thermoresponsive surfactant tubes: tuning
      macroscopic rheology by supramolecular assemblies.
AB  - In this article, we show that stimuli-induced microscopic transformations of self
      assembled surfactant structures can be used to tune the macroscopic bulk and
      interfacial rheological properties. Previously, we had described the formation of
      micron-sized 12-hydroxystearic acid tubes having a temperature-tunable diameter
      in the bulk, and also adsorbing at the air-water interface. We report now a
      detailed study of the bulk and interfacial rheological properties of this
      solution of thermoresponsive tubes as a function of temperature. In the bulk, the
      structural modifications of tubes with temperature lead to sharp and non
      monotonous changes of rheological behavior. As well, at the air-water interface,
      the interfacial layer is shifted several times from rigid-like to fluid-like as
      the temperature is increased, due to morphological changes of the adsorbed
      interfacial layer. The temperature-induced variations in the fatty acid
      supramolecular organization and the richness in structural transitions at this
      microscopic level lead to unique rheological responses in comparison with
      conventional surfactant systems. Also, this study provides new insights into the
      required packing conditions for the jamming of anisotropic soft objects and
      highlights the fact that this system becomes glassy under heating. Due to these
      unique macroscopic properties both in the bulk and at the interface, this simple
      system with stimuli-responsive viscoelasticity is of interest for their potential
      applications in pharmacology or cosmetic formulations. 

PMID- 24663154
TI  - A genomewide association study for average daily gain in Italian Large White
      pigs.
AB  - Average daily gain is an important target trait in pig breeding programs. In this
      study we performed a genomewide association study for ADG in Italian Large White
      pigs using a selective genotyping approach. Two extreme and divergent groups of
      Italian Large White pigs (number 190 + 190) were selected among a population of
      about 10,000 performance tested gilts (EBV for ADG in the 2 groups were -30 +/-
      14 g and 81 +/- 12 g, respectively) and genotyped with the Illumina PorcineSNP60
      BeadChip. Association analysis was performed treating the pigs of the 2 extreme
      groups as cases and controls after correction for family-based stratification. A
      total of 127 SNP resulted significantly associated with ADG (P nominal value
      [P(raw)] < 2.0 * 10(-7), P < 0.01 Bonferroni corrected [P(Bonferroni)] < 0.01,
      false discovery rate < 7.76 * 10(-5)). Another 102 SNP were suggestively
      associated with the target trait (P(raw) between 2.0 * 10(-7) and 2.02 * 10(-6),
      P(Bonferroni) < 0.10, false discovery rate < 4.19 * 10(-4)). These SNP were
      located on all autosomes and on porcine chromosome (SSC) X. The largest number of
      SNP within this list was on SSC5 (n = 42), SSC7 (34), SSC6 (30), SSC4 (23), and
      SSC16 (16). These chromosomes were richer in significant or suggestively
      significant markers than expected (P < 0.001). A quite high number of these SNP
      (n = 23) were associated with backfat thickness in a previous genomewide
      association study performed in the same pig population, confirming the negative
      correlation between the 2 traits. Two or more SNP targeted the same gene: IGSF3
      and HS2ST1 (SSC4), OTOGL (SSC5), FTO region (SSC6), and MYLK4 and MCUR1 (SSC7).
      Other regions that were associated with ADG in previous candidate gene studies
      (e.g., MC4R on SSC1, IGF2 and LDHA on SSC2, MUC4 on SSC13) 1) included markers
      with P(raw) < 0.01 that, however, did not pass the stringent threshold of
      significance adopted in this study or 2) could not be tested because not assigned
      to the Sscrofa10.2 genome version. Functional annotation of the significant
      regions using Gene Ontology suggested that many and complex processes at
      different levels are involved in affecting ADG, indicating the complexity of the
      genetic factors controlling this ultimate phenotype. The obtained results may
      contribute to understand the genetic mechanisms determining ADG that could open
      new perspectives to improve selection efficiency in this breed.

PMID- 24663151
TI  - The 2.1 A resolution structure of cyanopindolol-bound beta1-adrenoceptor
      identifies an intramembrane Na+ ion that stabilises the ligand-free receptor.
AB  - The beta1-adrenoceptor (beta1AR) is a G protein-coupled receptor (GPCR) that is
      activated by the endogenous agonists adrenaline and noradrenaline. We have
      determined the structure of an ultra-thermostable beta1AR mutant bound to the
      weak partial agonist cyanopindolol to 2.1 A resolution. High-quality crystals
      (100 MUm plates) were grown in lipidic cubic phase without the assistance of a T4
      lysozyme or BRIL fusion in cytoplasmic loop 3, which is commonly employed for
      GPCR crystallisation. An intramembrane Na+ ion was identified co-ordinated to
      Asp872.50, Ser1283.39 and 3 water molecules, which is part of a more extensive
      network of water molecules in a cavity formed between transmembrane helices 1, 2,
      3, 6 and 7. Remarkably, this water network and Na+ ion is highly conserved
      between beta1AR and the adenosine A2A receptor (rmsd of 0.3 A), despite an
      overall rmsd of 2.4 A for all Calpha atoms and only 23% amino acid identity in
      the transmembrane regions. The affinity of agonist binding and nanobody Nb80
      binding to beta1AR is unaffected by Na+ ions, but the stability of the receptor
      is decreased by 7.5 degrees C in the absence of Na+. Mutation of amino acid side
      chains that are involved in the co-ordination of either Na+ or water molecules in
      the network decreases the stability of beta1AR by 5-10 degrees C. The data
      suggest that the intramembrane Na+ and associated water network stabilise the
      ligand-free state of beta1AR, but still permits the receptor to form the
      activated state which involves the collapse of the Na+ binding pocket on agonist
      binding. 

PMID- 24663155
TI  - CELL BIOLOGY SYMPOSIUM: perspectives: possible roles of polymorphonuclear
      neutrophils in angiogenesis and lymphangiogenesis in the corpus luteum during
      development and early pregnancy in ruminants.
AB  - The establishment of pregnancy requires well-balanced regulation of the endocrine
      and immune systems and involves interactions among the conceptus, oviduct-uterus,
      and corpus luteum (CL). In particular, a rapid increase in plasma progesterone
      during the first week after ovulation is critical for the growth of the conceptus
      and successful pregnancy in cattle. Events involved in maternal recognition of
      pregnancy (MRP) may commence within 1 wk from AI, when interferon-stimulated gene
      expression in circulating polymorphonuclear neutrophils (PMN) increases in
      pregnant cows. To regulate optimal endocrine conditions within this time, the CL
      must develop rapidly, with active angiogenesis and lymphangiogenesis. The major
      angiogenic factors, vascular endothelial growth factor and fibroblast growth
      factor 2, contribute to the development of the CL but may also act as
      chemoattractants for PMN. Indeed, the number of PMN is greatest in the new CL,
      where PMN together with IL-8 induce active angiogenesis and lymphangiogenesis.
      During MRP, the conceptus secretes interferon tau (IFNT), which prevents CL
      regression by inhibiting luteolytic release of PGF2alpha from uterine
      endometrium. In addition, IFNT and PGE2 reach the CL and may contribute to
      desensitizing the CL to the luteolytic effects of PGF2alpha. In the bovine CL,
      lymphangiogenesis, stimulated by IFNT, may occur during MRP, and thus a shift of
      local immunity might occur at this timing. The aforementioned evidence supports
      the possible involvement of PMN in the establishment of pregnancy via CL
      regulation. Further investigation could expand our understanding of the
      communication between zygotes, PMN, and reproductive organs during early
      pregnancy. This should provide new insight into the contribution of neutrophils
      to CL function and immune tolerance during early pregnancy in ruminants. 

PMID- 24663156
TI  - Effect of rate of weight gain of steers during the stocker phase. III. Gene
      expression of adipose tissues and skeletal muscle in growing-finishing beef
      cattle.
AB  - The objective of this study was to determine the impact of stocker production
      systems differing in growth rate on differential adipogenic and lipogenic gene
      expression of intramuscular (IM), subcutaneous (SC), and perirenal (PR) adipose
      tissues. Angus steers were assigned to 4 stocker cattle production systems in 2
      consecutive years: 1) cottonseed meal-based supplement while grazing dormant
      native range (CON), 2) ground corn/soybean meal-based supplement while grazing
      dormant native range (CORN), 3) grazing wheat pasture at a high stocking rate for
      a low rate of BW gain (LGWP), and 4) grazing wheat pasture at a low stocking rate
      for a high rate of BW gain (HGWP). Steers were harvested during the stocker phase
      at similar age (different carcass weight) in Exp. 1 (3 steers/treatment) or at
      similar carcass weight in Exp. 2 (4 steers/treatment). Adipose tissues were
      analyzed for mRNA expression of adipogenic (peroxisome proliferator activated
      receptor gamma [PPARgamma], sterol regulatory element binding factor 1 [SREBF1],
      CAATT/enhancer binding protein beta, and delta-like homolog 1) and lipogenic
      (glycerol-3-phosphate dehydrogenase [GPDH], fatty acid synthase [FASN], and
      diacylglycerol acyltransferase 2 [DGAT2]) genes. Multivariate analysis was used
      to evaluate the expression of adipogenic or lipogenic genes collectively. There
      was not a treatment * adipose tissue interaction (F-test, P > 0.15) when steers
      were harvested at similar age, but a treatment * adipose tissue interaction (F
      test, P < 0.05) was evident when steers were harvested at similar carcass weight.
      At similar carcass weight, treatment had no effect (P > 0.10) on the canonical
      variate of adipogenic or lipogenic mRNA expression in IM adipose tissue, but
      faster rates of gain of LGWP and HGWP steers increased (P < 0.10) the canonical
      variate of adipogenic and lipogenic mRNA expression in SC and PR adipose tissue
      compared with CON and CORN steers. Strong positive correlations (P < 0.05) of
      PPARgamma, SREBF1, GPDH, FASN, and DGAT2 mRNA expression with the canonical
      variate indicate that these genes strongly influenced differences between
      treatments and adipose tissues. These results suggest that contrary to our
      hypothesis rate of gain has little influence on differentiation and lipid
      synthesis of IM adipose tissue at similar carcass weight but faster rates of gain
      increase differentiation and lipid synthesis of SC and PR adipose tissue even at
      similar carcass weight. 

PMID- 24663157
TI  - Comparison of a 16- versus a 19-day interval between controlled internal drug
      release removal and prostaglandin F2alpha following a 14-day controlled internal
      drug release treatment and fixed-time artificial insemination in postpartum beef
      cows.
AB  - This experiment compared 2 long-term controlled internal drug release (CIDR)
      based protocols to synchronize estrus before fixed-time artificial insemination
      (FTAI) in postpartum beef cows. Cows were assigned to treatments by age, BCS, and
      days postpartum. Cows assigned to the 14- to 19-d CIDR-PGF2alpha protocol (n =
      196) received CIDR inserts (1.38 g progesterone [P4]) from d 0 to 14 and
      PGF2alpha (25 mg, i.m.) 19 d after CIDR removal on d 33. Cows assigned to the 14
      to-16-d CIDR-PGF2alpha protocol (n = 195) received CIDR inserts from d 3 to 17
      and PGF2alpha 16 d after CIDR removal on d 33. Cows were artificially inseminated
      on d 36, 72 h after PGF2alpha, with GnRH (100 MUg, i.m.) at FTAI. Cows were
      exposed for natural service 14 d after FTAI for 75 d. Blood samples for P4 were
      collected at d -10 and 0 to determine pretreatment estrous cyclicity status and
      again at PGF2alpha. Blood samples for estradiol (E2) were collected at PGF2alpha
      and FTAI. HeatWatch estrus detection transmitters were used from CIDR removal
      until FTAI to determine onset of estrus after CIDR removal and PGF2alpha.
      Dominant follicle diameter was determined at PGF2alpha and FTAI. Pregnancy
      diagnosis was performed 70 d after FTAI and confirmed at d 140 of gestation.
      Estrous response after CIDR removal was similar between treatments. Cows in both
      treatments had similar size dominant follicles on d 33 at PGF2alpha and d 36 at
      FTAI. Progesterone at PGF2alpha was greater (P = 0.03) for 14-to-16-d compared to
      14-to-19-d treated cows. Mean concentrations of E2 at PGF2alpha were similar
      between treatments but were greater (P = 0.01) at FTAI for 14-to-16-d compared to
      14-to-19-d treated cows. Estrous response after PGF2alpha was greater (P < 0.01)
      for 14-to-19-d compared to 14-to-16-d treated cows (47.4 vs. 29.7%,
      respectively). Pregnancy rate resulting from FTAI was affected by the treatment *
      age group interaction (P = 0.08). Pregnancy rate after FTAI among cows >= 4 yr
      tended to be greater (P = 0.06) for 14-to-19-d compared to the 14-to-16-d treated
      cows, suggesting that the 14-to-19-d schedule works better for older age cows
      compared with the 14-to-16-d schedule. Final pregnancy rates were similar between
      the 2 treatments. In summary, these data indicate that a range in intervals from
      CIDR removal to PGF2alpha may be feasible when using long-term CIDR-based
      protocols in cows and raise questions that warrant further study regarding the
      benefits of extending this interval based on cow age.

PMID- 24663158
TI  - Effect of day of mixing gestating sows on measures of reproductive performance
      and animal welfare.
AB  - Effects of day of mixing sows after breeding were measured for reproduction and
      welfare on a commercial research farm. Sows (n = 1,436) were weaned into stalls
      for breeding, and groups of sows were assigned to 1) no mixing and housed in
      individual stalls (STL), 2) mixed on d 3 to 7 after breeding (D3), 3) mixed on d
      13 to 17 after breeding (D14), or 4) mixed 35 d after breeding (D35). Mixed sows
      were moved into pens (n = 58 sows/pen) with an electronic sow feeding station and
      maintained as a static group. In the first 12 d after mixing or movement into STL
      (period 1), sows were assessed for lameness and lesions every 3 d and then every
      2 wk until farrowing (period 2). Cortisol and fights were measured in period 1.
      Conception rates were reduced (P < 0.005) in D3 (87.1%) and D14 (89.2%) compared
      to D35 (92.2%) and STL (96.2%). Farrowing rates were lower (P < 0.0001) in D3
      (82.8%) compared to D35 (90.5%) and STL (96.2%), but litter size was not (P >=
      0.20) affected by mixing. The proportion of sows bred within 10 d of weaning was
      reduced (P < 0.05) for D14 compared to STL, but D3 and D35 did not differ among
      treatments. Number of fights 24 h after mixing was less (P < 0.0001) for D14
      compared to D3 and D35 groups, and serum cortisol was greater (P < 0.05) for D35
      compared to STL and D3. From period 1 to 2, lameness increased in D3 and
      decreased in D35 but did not change for D14 and STL (treatment * period, P <
      0.05), whereas leg inflammation did not differ (P > 0.10) among treatments. Head
      and body lesion scores declined from period 1 to 2 in all mix groups, whereas
      vulva lesions increased in the D3 and D35 but did not change in D14 and STL
      (treatment * period, P < 0.0001). These results suggest STL can improve most
      measures of welfare compared to mixing in groups. However, when mixing sows,
      assessments for reproductive performance and welfare may change from gestation to
      farrowing. The poorest reproductive performance and welfare was observed when
      sows were mixed 3 to 7 d after breeding. There were few differences between the
      D14 and D35 treatments in reproduction or welfare, but D14--not D35--differed
      from STL in weaned sows rebred. Overall, results of this trial suggest that, even
      though any of the mixing days can result in acceptable measures of reproduction,
      there are clear effects of day of mixing on fertility and welfare, and special
      attention should be focused on the long-term reproductive and welfare
      consequences.

PMID- 24663159
TI  - Effects of USDA carcass maturity on sensory attributes of beef produced by grain
      finished steers and heifers classified as less than 30 months old using
      dentition.
AB  - This study compared sensory properties of LM steaks from A maturity and B
      maturity or older carcasses that were produced by grain-finished steers and
      heifers classified as less than 30 mo old at the time of slaughter using
      dentition. Carcasses were selected to represent 2 maturity groups and 3 marbling
      categories within each maturity group, resulting in 6 maturity * marbling
      subclasses, each subclass consisting of 75 carcasses. Maturity groups consisted
      of carcasses classified by USDA graders as either A(00) to A(99) overall (A)
      maturity or B(00) to C(99) overall (B-C) maturity; marbling categories consisted
      of carcasses with instrument marbling scores of Slight (SL), Small (SM), or
      Modest(00) or greater (MT+). Carcasses were selected in pairs so that each
      carcass chosen to represent the B-C maturity group was paired with an A maturity
      carcass of the same sex and marbling score (+/- 30 marbling units). Strip loin
      (LM) steaks were obtained from both sides of each carcass. After a 14-d aging
      period, 1 LM steak was measured for Warner-Bratzler shear force (WBSF) and slice
      shear force (SSF), whereas the other LM steak was used for sensory analysis by a
      trained descriptive attribute panel. No differences (P > 0.05) in WBSF, SSF, or
      sensory panel ratings for tenderness, juiciness, or flavor were detected between
      LM steaks from carcasses classified as A maturity and steaks from B-C maturity
      carcasses. However, marbling categories effectively stratified carcasses (MT+ >
      SM > SL) according to differences (P < 0.0001) in LM tenderness, juiciness,
      meaty/brothy flavor, and buttery/beef fat flavor. Increased marbling also was
      associated with lesser (P < 0.01) intensities of bloody/serumy and livery/organy
      flavors and reduced (P < 0.01) values for WBSF and SSF. Of the traits tested,
      only bloody/serumy flavor was affected (P < 0.05) by the maturity * marbling
      interaction. Interaction means showed that LM steaks from B-C maturity carcasses
      with SL marbling had a less intense bloody/serumy flavor than did steaks from A
      maturity carcasses with SL marbling. Results of this study suggest that, when
      applied to carcasses from grain-finished cattle whose dental ages are less than
      30 mo old at the time of slaughter, USDA quality grades would be no less
      effective in identifying eating quality differences if the A and B-C maturity
      groups were combined and quality grades were assigned using only marbling.

PMID- 24663160
TI  - The effect of equine metabolic syndrome on the ovarian follicular environment.
AB  - Obesity in many species is associated with reduced fertility and increased risk
      of metabolic disorders and cardiovascular dysfunction in offspring. Equine
      metabolic syndrome (EMS) is associated with obesity and characterized by insulin
      resistance, decreased adiponectin, and elevated insulin, leptin, and pro
      inflammatory cytokines. These alterations can potentially disrupt follicular
      development and impair fertility. We hypothesized that mares with EMS have an
      altered follicular environment when compared to their normal counterparts,
      affecting gene regulation for follicle and oocyte maturation. Samples were
      collected from light-horse mares (11 to 27 yr) in a clinical assisted
      reproductive program. Mares were screened based on phenotype. Insulin sensitivity
      was determined by using two proxies, the reciprocal of the square root of insulin
      (RISQI) and the modified insulin-to-glucose ratio (MIRG). Insulin resistant mares
      (RISQI < 0.32 and MIRG > 5.50) were allocated to the EMS group (n = 8), and the
      remaining mares were considered normal controls (CON, n = 12). Follicular fluid
      (FF) and granulosa cells (GC) from preovulatory follicles were aspirated 24 +/- 2
      h after administration of a GnRH analog (SucroMate, 0.9 to 1.4 mg, i.m.) and hCG
      (Chorion, 1500 to 2000 IU, i.v.). After an overnight fast, blood was collected on
      the morning of follicle aspiration to evaluate serum concentrations of insulin,
      leptin, adiponectin, and inflammatory cytokines. Expression of 32 genes related
      to metabolism, follicle maturation, and oocyte maturation were assessed in GC.
      Concentrations of insulin, leptin, adiponectin, and cytokines were highly
      correlated between serum and FF (P < 0.001). Insulin was lower (P < 0.001) in
      serum and FF of CON compared to EMS, but leptin and IL1beta tended (P = 0.07 and
      P = 0.10, respectively) to be lower in FF of CON than EMS. Tumor necrosis factor
      alpha in serum and FF was lower (P < 0.07 and P < 0.05, respectively) in CON than
      EMS. Conversely, adiponectin was higher (P < 0.05) in serum and FF in CON versus
      EMS. In GC from CON when compared to EMS, gene expression for epiregulin was
      elevated (P < 0.05) and tissue inhibitor of matrix metalloproteinase-2 tended to
      be lower (P = 0.09). Our findings demonstrate that the intrafollicular
      environment in the mare is influenced by metabolic disease, consistent with
      findings in other species. Influences on follicular development, oocyte
      maturation, and subsequent offspring by perturbations due to metabolic disease
      need further study. 

PMID- 24663161
TI  - Effects of gestation housing system and floor type during lactation on locomotory
      ability; body, limb, and claw lesions; and lying-down behavior of lactating sows.
AB  - This study evaluated the influence of housing system during gestation and floor
      type during lactation on the welfare and lying-down behavior of lactating sows.
      Multiparous sows (n = 85) were housed either in individual gestation stalls (n =
      42) or loose (n = 43) in a single dynamic group with 2 electronic sow feeders
      moved to farrowing crates on either slatted steel (n = 48) or cast iron (n = 37)
      flooring. Lameness (0 = normal to 5 = severely lame) was scored on transfer to
      the farrowing crate (-5 d). Limb and body lesions were recorded on -5 d, 24 h
      after entering the farrowing crate (-4 d), 10-d postpartum, and before weaning.
      Claw lesions were recorded on -5 d and before weaning, whereas all behavioral
      observations were made on -5, -4, and 10 d. Median (Me) scores were calculated
      for claw, body, and limb lesions and classified as either less than or equal to
      the Me or greater than the Me lesion scores. Sows were classified as nonlame (<=
      1) or lame (>= 2). Loose-housed sows had an increased (P < 0.01) risk of
      lameness; a reduced (P < 0.05) risk for claw lesions, particularly white line
      damage, horizontal wall cracks, and dewclaw injuries; and a reduced (P < 0.05)
      risk for calluses and bursitis on the limbs compared to stall-housed sows. Sows
      housed on cast iron floors during lactation had a reduced (P < 0.01) risk for
      heel overgrowth and erosion and heel-sole cracks compared with sows on slatted
      steel floors. There was no (P > 0.05) association between flooring type during
      lactation and body lesion score. On -4 d, loose-housed sows had a shorter latency
      to lie down (P < 0.01), spent more time inactive (P < 0.05), and shifted weight
      between the limbs more often (P = 0.05) while standing compared with stall-housed
      sows. Lame sows had a shorter (P < 0.01) latency to lie down compared to nonlame
      sows on -5 and -4 d. In conclusion, there was an increased risk of lameness in
      sows housed loose compared to those housed in gestation stalls on transfer to the
      farrowing crate. Claw health deteriorated in the farrowing crate regardless of
      gestation housing or floor type but the deterioration in claw health was
      increased on slatted steel compared to on cast iron. 

PMID- 24663162
TI  - Space allowance and high fiber diet impact performance and behavior of group-kept
      gestating sows.
AB  - Identifying and optimizing housing and management systems that improve the well
      being of the gestating sow is essential to sustaining animal agriculture.
      Therefore, the impact of 2 floor-space allowances and a high-fiber gestation diet
      on dry group-housed sows were evaluated using multiple measures of well-being.
      Groups of 10 multiparous sows/pen (n = 221) were assigned randomly to treatments
      in a 2 * 2 factorial arrangement to either a corn-soybean meal diet (CTL) or corn
      soybean meal diet supplemented with soybean hulls and wheat middlings (FBR), and
      floor-space allowance of either 1.7 or 2.3 m(2)/sow. Sow BW, backfat (BF), and
      body condition score (BCS) were all recorded on d 34, 65, 90, and 110 of
      gestation, whereas skin lesions were scored on d 34, every 2 d for the first 2-wk
      postmixing, and then biweekly throughout gestation. Blood sample was collected
      only on d 34 for cortisol (baseline), and samples were collected on d 90 of
      gestation for other measures including cortisol. Behavior was registered on
      multiple days throughout gestation. Sows fed FBR and kept at 1.7 m(2) produced
      heavier litter and weaning weights and greater number of piglets born alive,
      compared to sows fed FBR but kept at 2.3 m(2) of floor space (diet * floor space,
      P <= 0.04). Sows fed FBR and kept at 1.7 m(2) performed fewer oral-nasal-facial
      and sham-chew behaviors than sows fed CTL and kept at the same floor space (diet
      * floor space, P <= 0.044). Sows kept at 1.7 m(2) of floor space had a greater (P
      < 0.05) total lesion severity score than sows kept at 2.3 m(2)/sow, and vulva
      lesion scores were more (P < 0.02) severe among CTL-fed sows than FBR-fed sows.
      Parities 2 and 3 sows fed FBR and kept at 1.7 m(2) of floor space were heavier (P
      < 0.001) than sows fed the same diet but kept at 2.3 m(2). These results indicate
      that keeping small groups of pregnant sows at a minimum floor-space allowance of
      1.7 m(2)/sow and floor feeding these sows a high-fiber diet can improve short
      term sow well-being. 

PMID- 24663163
TI  - Update on human health concerns of recombinant bovine somatotropin use in dairy
      cows.
AB  - The 20 yr of commercial use of recombinant bovine somatotropin (rbST) in the
      United States provide the backdrop for reviewing the outcome of use on human
      health issues by the upcoming 78th meeting of the Joint Food and Agriculture
      Organization of the United Nations (FAO)/World Health Organization (WHO) Expert
      Committee on Food Additives. These results and further advancements in scientific
      knowledge indicate there are no new human health issues related to the use of
      rbST by the dairy industry. Use of rbST has no effect on the micro- and
      macrocomposition of milk. Also, no evidence exists that rbST use has increased
      human exposure to antibiotic residues in milk. Concerns that IGF-I present in
      milk could have biological effects on humans have been allayed by studies showing
      that oral consumption of IGF-I by humans has little or no biological activity.
      Additionally, concentrations of IGF-I in digestive tract fluids of humans far
      exceed any IGF-I consumed when drinking milk. Furthermore, chronic
      supplementation of cows with rbST does not increase concentrations of milk IGF-I
      outside the range typically observed for effects of farm, parity, or stage of
      lactation. Use of rbST has not affected expression of retroviruses in cattle or
      posed an increased risk to human health from retroviruses in cattle. Furthermore,
      risk for development of type 1 or type 2 diabetes has not increased in children
      or adults consuming milk and dairy products from rbST-supplemented cows. Overall,
      milk and dairy products provide essential nutrients and related benefits in
      health maintenance and the prevention of chronic diseases. 

PMID- 24663164
TI  - Developing a computer-controlled simulated digestion system to predict the
      concentration of metabolizable energy of feedstuffs for rooster.
AB  - Four experiments were conducted to evaluate the effectiveness of a computer
      controlled simulated digestion system (CCSDS) for predicting apparent
      metabolizable energy (AME) and true metabolizable energy (TME) using in vitro
      digestible energy (IVDE) content of feeds for roosters. In Exp. 1, the
      repeatability of the IVDE assay was tested in corn, wheat, rapeseed meal, and
      cottonseed meal with 3 assays of each sample and each with 5 replicates of the
      same sample. In Exp. 2, the additivity of IVDE concentration in corn, soybean
      meal, and cottonseed meal was tested by comparing determined IVDE values of the
      complete diet with values predicted from measurements on individual ingredients.
      In Exp. 3, linear models to predict AME and TME based on IVDE were developed with
      16 calibration samples. In Exp. 4, the accuracy of prediction models was tested
      by the differences between predicted and determined values for AME or TME of 6
      ingredients and 4 diets. In Exp. 1, the mean CV of IVDE was 0.88% (range = 0.20
      to 2.14%) for corn, wheat, rapeseed meal, and cottonseed meal. No difference in
      IVDE was observed between 3 assays of an ingredient, indicating that the IVDE
      assay is repeatable under these conditions. In Exp. 2, minimal differences (<21
      kcal/kg) were observed between determined and calculated IVDE of 3 complete diets
      formulated with corn, soybean meal, and cottonseed meal, demonstrating that the
      IVDE values are additive in a complete diet. In Exp. 3, linear relationships
      between AME and IVDE and between TME and IVDE were observed in 16 calibration
      samples: AME = 1.062 * IVDE - 530 (R(2) = 0.97, residual standard deviation [RSD]
      = 146 kcal/kg, P < 0.001) and TME = 1.050 * IVDE - 16 (R(2) = 0.97, RSD = 148
      kcal/kg, P < 0.001). Differences of less than 100 kcal/kg were observed between
      determined and predicted values in 10 and 9 of the 16 calibration samples for AME
      and TME, respectively. In Exp. 4, differences of less than 100 kcal/kg between
      determined and predicted values were observed in 3 and 4 of the 6 ingredient
      samples for AME and TME, respectively, and all 4 diets showed the differences of
      less than 25 kcal/kg between determined and predicted AME or TME. Our results
      indicate that the CCSDS is repeatable and additive. This system accurately
      predicted AME or TME on 17 of the 26 samples and may be a promising method to
      predict the energetic values of feed for poultry. 

PMID- 24663165
TI  - The duration of time that beef cattle are fed a high-grain diet affects feed
      sorting behavior both before and after acute ruminal acidosis1,2.
AB  - The objective of this study was to determine how duration of time that cattle are
      fed a high-grain diet affects feed sorting, both before and after an episode of
      acute ruminal acidosis. Sixteen Angus heifers (261 +/- 6.1 kg; BW +/- SEM) were
      assigned to 1 of 4 blocks and fed a backgrounding (BG) diet (60% forage, DM
      basis). Within block, heifers were randomly assigned to 1 of 2 treatments
      differing in days fed a high-grain (HG; 9% forage, DM basis, fed ad libitum) diet
      before a ruminal acidosis challenge: 34 d for long adapted (LA) and 8 d for short
      adapted (SA). Ruminal acidosis was induced by restricting feed to 50% of DMI as a
      proportion of BW (determined individually for each heifer) for 24 h followed by
      an intraruminal infusion of ground barley at 10% of DMI as a proportion of BW
      measured before feed restriction. Feed and orts were sampled during the BG
      period, the first 26 d on the HG diet (only for LA cattle), the 8-d baseline
      (BASE) period, on the day of the ruminal acidosis challenge (CH), and during 2
      consecutive 8-d recovery periods (REC1 and REC2) for each heifer and subjected to
      particle size analysis: 19-mm (long), 8-mm (medium), and 1.18-mm (short) screens
      and a pan (fine). On the BG diet, sorting for medium particles tended to be
      greater (104.2 vs. 102.1%; P = 0.07) for LA heifers than SA heifers, while
      sorting against short particles was greater (98.2 vs. 100.0%; P = 0.05) for LA
      heifers. During the first 26 d on the HG diet, LA cattle sorted for (P < 0.001)
      long (118.8%), medium (117.8%), and short (104.1%) particles and sorted against
      (P < 0.001) fine particles (45.3%). This sorting pattern was consistent for LA
      heifers during BASE period, CH day, and recovery periods, across which SA heifers
      exhibited less sorting (P <= 0.1). Greater duration of pH < 5.5 during the BASE
      period was associated with greater sorting for long particles (R(2) = 0.75, P =
      0.01) in LA heifers and for long (R(2) = 0.49, P = 0.05) and medium (R(2) = 0.88,
      P < 0.001) particles in SA heifers. Long-adapted heifers linearly increased the
      extent of sorting for long (P = 0.007) and medium (P < 0.001) particles and
      against fine particles (P = 0.05) during the days following the challenge to a
      greater extent than SA heifers. Overall, the results demonstrate that longer-term
      exposure of beef heifers to a HG diet, which caused persistent low rumen pH,
      influenced feed sorting of heifers, both before and after an induced bout of
      acute ruminal acidosis, in a manner that would help attenuate the effects of
      acidosis. 

PMID- 24663166
TI  - Effect of residual feed intake on hypothalamic gene expression and meat quality
      in Angus-sired cattle grown during the hot season.
AB  - The relationship between heat stress, meat quality, and residual feed intake
      (RFI) is unknown in growing steers. To address this issue, high RFI (HRFI) and
      low RFI (LRFI) individuals were compared by assessing RFI in 48 Angus-sired
      steers during a 70-d feeding trial conducted during July through September to
      identify steers with calculated RFI at least 2 SD apart. The association of RFI
      with indices of meat quality and expression of genes within hypothalamic and
      adipose tissue was then determined in LRFI and HRFI steers. While on test, feed
      intake was recorded daily with BW and hip heights recorded every 14 d. Ultrasound
      measurements of rib eye area (REA) and backfat (BF) were recorded initially and
      before harvest. Carcass and growth data were analyzed using a mixed model with
      RFI level (LRFI and HRFI) as the independent variable. The least square means for
      RFI were -1.2 and 0.99 kg DMI/d, respectively, for the LRFI and HRFI cohorts (P <
      0.0001). Dry matter intake was higher for the HRFI individuals versus the LRFI
      steers (P < 0.0001) while on-test gain was not different (P < 0.95). Marbling
      score was greater in LRFI than HRFI steers (P < 0.05). However, there were no
      differences in REA (P < 0.53), BF (P < 0.65), yield grade (P < 0.24), or
      objective Hunter color measures between LRFI and HRFI steers indicating there was
      no consistent relationship between RFI and indices of meat quality. Hypothalamic
      neuropeptide Y (NPY), agouti related protein (AGRP), relaxin-3 (RLN3),
      melanocortin 3 receptor, and relaxin/insulin-like family peptide receptor 1
      (RXFP1) mRNA were expressed 280, 185, 202, 183, and 163% greater, respectively (P
      < 0.01), while proopiomelanocortin (POMC) mRNA was expressed 42% lower in LRFI
      than HRFI animals (P < 0.05). Hypothalamic GnRH mRNA expression was 67% lower
      while gonadotropin inhibiting hormone (GnIH) mRNA was 209% higher in LRFI than
      HRFI animals (P < 0.01). Pituitary expression of FSHbeta and LHbeta correlated to
      hypothalamic GnRH levels (P < 0.05) indicating changes in gene expression within
      the hypothalamus had functional consequences. Leptin mRNA expression levels were
      not different between adipose tissue of LRFI or HRFI steers (P < 0.84). These
      data indicate that animals with superior RFI evaluated during warm conditions
      have higher expression of orexigenic neuropeptide genes independent of the
      expression of adipose-derived leptin. Furthermore, the gonadotropin axis may also
      influence feed efficiency under these conditions. 

PMID- 24663167
TI  - Propionibacterium acidipropionici P169 and glucogenic precursors improve rumen
      fermentation of low-quality forage in beef cattle.
AB  - Cattle grazing dormant western rangelands may have a high ruminal acetate to
      propionate ratio (A:P) and may have low tissue clearance of acetate. Increasing
      propionate production could shift this ratio and improve animal performance. In
      Exp. 1, the effect of Propionibacterium acidipropionici P169 (PA) on forage
      digestibility and VFA production was evaluated in vitro using 2 substrates: 100%
      dormant warm-season grass extrusa and 50% sorghum-Sudan hay with 50% ground corn
      (DM basis). The objective of Exp. 2 was to evaluate the effect of PA or calcium
      propionate supplementation on digestibility, ruminal fermentation, acetate
      clearance, and BW change. Twelve 2-yr-old, pregnant Brangus heifers (BW = 416 +/-
      85 kg) were assigned to 1 of 3 treatments. All cattle were fed a basal ration of
      Old World Bluestem hay (Bothriochloa ischaemum; 5.8% CP and 76.5% NDF, DM basis)
      at 1.5% BW from d -10 to d 49. Treatments included a protein supplement (CON; 36%
      CP and 35% RUP, DM basis; 454 g/animal fed twice daily), CON plus 6 * 10(10) cfu
      PA/animal (BACT), and CON plus 80 g calcium propionate (PROP). After initiation
      of treatments (d 0), rumen fluid was collected via oral lavage every 3 d and
      analyzed for VFA, pH, and ammonia. Glucogenic potential of treatments was
      evaluated with an acetate tolerance test on d 49. In Exp. 1, PA addition
      increased (IVDMD; P < 0.001) and total VFA (P < 0.001) of 100% dormant warm
      season grass extrusa but not 50% sorghum-Sudan hay with 50% ground corn (P >=
      0.28). The addition of P169 decreased (P < 0.001) acetate, increased propionate
      (P < 0.001), and decreased A:P ratio (P < 0.001) for both substrates. In Exp. 2,
      total tract OM and NDF digestibility and ruminal pH, total VFA, and acetate did
      not differ (P >= 0.13) among treatments. Propionate concentration was least (P =
      0.001) for CON, intermediate for P169, and greatest for PROP. Conversely, A:P
      ratio was greatest (P < 0.004) for CON, intermediate for P169, and least for
      PROP. Acetate clearance did not differ (P = 0.69) among treatments.
      Propionibacterium acidipropionici P169 increased IVDMD and total VFA of low
      quality forage. Supplementation with PA and calcium propionate salts increased
      propionate and decreased A:P in the rumen. Supplementation of PA represents a
      potential way to increase ruminal propionate concentration when dormant forages
      are fed. 

PMID- 24663169
TI  - Delayed insemination of nonestrous cows improves pregnancy rates when using sex
      sorted semen in timed artificial insemination of suckled beef cows.
AB  - This experiment was designed to test the hypothesis that delayed insemination of
      nonestrous cows would increase pregnancy rates when using sex-sorted semen in
      conjunction with fixed-time artificial insemination (FTAI). Estrus was
      synchronized for 656 suckled beef cows with the 7-d CO-Synch + controlled
      internal drug release (CIDR) protocol (100 MUg GnRH + CIDR [1.38 g progesterone]
      on d 0, 25 mg PGF2alpha at CIDR removal on d 7, and 100 MUg GnRH on d 10, 66 h
      after CIDR removal). Estrus detection aids (Estrotect) were applied at PGF2alpha
      and CIDR removal on d 7, and estrous expression was recorded at GnRH on d 10.
      Cows were assigned to 1 of 3 treatments: 1) FTAI (concurrent with GnRH, 66 h
      after CIDR removal) with conventional semen regardless of estrous expression, 2)
      FTAI with sex-sorted semen regardless of estrous expression, or 3) FTAI with sex
      sorted semen for cows having expressed estrus and delayed AI 20 h after final
      GnRH for cows failing to express estrus. A treatment * estrous expression
      interaction was found (P < 0.0001). Higher pregnancy rates (P < 0.0001) were
      achieved with conventional semen (Treatment 1; 77%) than with sex-sorted semen
      (Treatments 2 and 3; 51 and 42%, respectively) among cows that expressed estrus.
      However, among cows that failed to express estrus, delayed insemination with sex
      sorted semen yielded higher (P < 0.0001) pregnancy rates than with sex-sorted
      semen at the standard time (Treatments 2 and 3; 3 versus 36%, respectively).
      Furthermore, among cows that failed to express estrus, FTAI pregnancy rates when
      using sex-sorted semen at the delayed time (36%) were comparable (P = 0.9) to
      those achieved using conventional semen at the standard time (Treatment 1; 37%).
      These results indicate that delaying AI of nonestrous cows by 20 h from the
      standard FTAI improves pregnancy rates when sex-sorted semen is used with FTAI. 

PMID- 24663168
TI  - Effects of castration method and frequency of intramuscular injections of
      ketoprofen on behavioral and physiological indicators of pain in beef cattle.
AB  - Two experiments were conducted to determine the effect of a single or multiple
      intramuscular (i.m.) injection of ketoprofen and castration technique on
      physiological and behavioral indicators of pain in beef calves. A total of 150
      bull calves (284.8 +/- 22.7 kg BW) were used in both experiments, each 1
      conducted as a 3 * 2 factorial design, where main factors included castration
      technique--no castration (CT), surgical (SU), or band (BA)--and drug
      administration--physiological solution (PS) or i.m. injection of ketoprofen (KP;
      3 mg Anafen/kg BW) in the neck of calves. Animals were weighed weekly during the
      experiment to calculate ADG. Behavioral responses indicative of pain and
      discomfort during the castration procedure were documented using a visual analog
      score (VAS) by an experienced observer who was blind to the treatments. Movements
      of the animals in the chute during castration were quantified using a strain
      gauge system mounted on the head gate to evaluate the escape response of the
      cattle. Pens were equipped with an automated feed bunk monitoring system enabling
      feed intake and feeding behavior to be continuously monitored for each
      individual. Thermographic images of the scrotal area were evaluated 24 and 0.5 h
      before castration, 0.5, 1, 24, 48, and 270 h postcastration, and weekly
      thereafter until the end of the trial. Blood samples were obtained postcastration
      to evaluate changes in total white blood cell (WBC) count and neutrophil-to
      lymphocyte (N:L) ratio. Saliva samples were taken 24 and 0.5 h before castration,
      immediately after castration, and 0.5, 1, 2, 5, 24, and 48 h and then 5, 7, and
      14 d after castration to determine cortisol concentration. Scrotal temperature,
      VAS, total WBC, N:L ratio, salivary cortisol, mobility, and pressure exerted in
      the chute were greater (P < 0.05) and ADG and feed intake were lower (P < 0.05)
      in SU than in CT animals within the first week after castration. Also, BA calves
      had a greater (P < 0.05) scrotal temperature around wk 4 after castration and a
      lower feed intake and ADG at wk 2 and 3 and wk 6 and 7 after castration,
      respectively, compared to CT. Treatment KP had limited effects on reducing the
      indicators of pain associated with SU or BA, suggesting that further studies will
      be needed to assess the posology of the i.m. administration of ketoprofen to
      improve the consistency of its effects as a pain mitigation strategy after
      castration.

PMID- 24663170
TI  - The effects of the duration and onset of light stimulation during incubation on
      the behavior, plasma melatonin levels, and productivity of broiler chickens.
AB  - Light stimulation during incubation can affect the behavior, health, and
      performance of poultry posthatch. However, there has been relatively little work
      systematically assessing the pattern of light stimulation needed to produce these
      effects or the mechanism underlying them. We conducted 2 experiments to assess
      the effects of duration and onset of light exposure during incubation on Cobb 500
      broiler chickens. In the first, eggs (n = 1,404) were incubated under
      photoperiods of either 0 h of light and 24 h of darkness (0 L:24 D), 1 h of light
      and 23 h of darkness (1 L:23 D), 6 h of light and 18 h of darkness (6L:18D), or
      12 h of light and 12 h of darkness (12L:12D). In the second, eggs (n = 1,008)
      were incubated in either complete darkness or under 12L:12D, which was applied
      either for the entire incubation period or with light onset beginning at either 7
      or 14 d of incubation. Broilers were then housed in floor pens under a 12L:12D
      cycle posthatch. Measurements included performance outcomes, plasma melatonin,
      general behavioral activity assessed using passive infrared detection, and
      feeding activity assessed using automated continuous monitoring of feed intake at
      wk 5 of age. There were no treatment differences in hatchability, mortality,
      growth, feed consumption, feed conversion ratio, overall feeding behavior
      activity, or general behavioral activity over a 24-h period in either experiment.
      However, broilers incubated under 12L:12D fed more (P < 0.05) than the 0 L:24 D
      broilers during the first 3 h after the lights came on in Exp. 1 and during the
      first hour after the lights came on in Exp. 2. In Exp. 1, general activity levels
      measured using passive infrared detection at night also differed (P = 0.05), with
      0 L:24 D more active than 12L:12D. There was a treatment difference between the 0
      L:12 D and 12 L:12 D in their plasma melatonin rhythms during d 19 of incubation,
      but this difference had disappeared when broilers were sampled at wk 5 posthatch.
      The results of this study indicate that providing 12 h of light during incubation
      can have a long-lasting effect on the diurnal rhythms of behavior, although the
      mechanism underlying this does not appear to be related to a persistent change in
      melatonin rhythm.

PMID- 24663171
TI  - Intake estimation of horses grazing tall fescue (Lolium arundinaceum) or fed tall
      fescue hay.
AB  - Six mature geldings of light horse breeds (557 +/- 37 kg) were randomly assigned
      to a nontoxic endophyte-infected tall fescue hay (n = 3) or pasture treatment (n
      = 3) in a crossover design with 14-d periods to estimate DMI with alkane markers
      and to compare DMI of hay and pasture. When fed pasture, horses were housed in
      stalls from 0700 to 1300 h daily with access to water and then grazed pasture as
      a group in a single 0.4 ha pasture from 1300 to 0700 h. When fed hay, horses were
      maintained individually in stalls and given access to hay ad libitum from 1300 to
      0700 h. All horses were individually fed 225 g oats twice daily treated with
      hexatriacontane (C36; external marker) and fecal samples were collected at 0700
      and 1900 h on d 10 to 14. Fecal samples were mixed, dried, subsampled, and
      analyzed for tritriacontane (C33) and hentriacontane (C31) as internal markers
      and C36 as the external marker using gas chromatography. Estimated hay DMI using
      either C33 (1.75 kg/100 kg BW) or C31 (1.74 kg/100 kg BW) as internal alkane
      marker did not differ (P = 0.55) from measured hay DMI (1.70 kg/100 kg BW).
      Pasture DMI and DM digestibility (DMD) estimated with C31 (2.24 kg/100 kg BW and
      53.1 g/100 g DMI) or with C33 (2.34 kg/100 kg BW and 56.2 g/100 g DMI) was
      greater (P = 0.05) than hay DMI and DMD (1.74 kg/100 kg BW and 44.5 g/100 g DMI).
      Intake estimated with C33 or C31 did not differ (P = 0.35) during hay or pasture.
      In conclusion, alkanes can be used to estimate pasture or hay DMI and DMD, and
      pasture intake exceeded hay intake when offered ad libitum. 

PMID- 24663172
TI  - Effect of crowding stress and Escherichia coli K88+ challenge in nursery pigs
      supplemented with anti-Escherichia coli K88+ probiotics.
AB  - Under commercial conditions and during production periods, pigs are generally
      exposed to a number of stressors that may have direct or indirect influence on
      their performance and general health. As a result, environmental stressors can
      influence the productivity as well as the onset and severity of infectious
      diseases. The aim of this study was to investigate the effects of crowding stress
      on performance and some immunological responses in piglets challenged with
      enterotoxigenic Escherichia coli (ETEC) K88(+) and fed diets containing anti-ETEC
      probiotic strains derived from E. coli in a 3-wk trial. Ninety-six piglets at 20
      +/- 1 d of age were randomly assigned to 6 experimental treatments with 3
      pigs/pen and 5 replicates/treatment and fed a basal mash diet. To model stress,
      piglets were housed in 2 kinds of pens: standard floor allowance (SFA; no stress)
      and half standard floor allowance (HSFA; stressed). The treatments were 1)
      control pigs with SFA, 2) control pigs with HSFA, 3) pigs with SFA and challenged
      with ETEC (ESFA), 4) pigs with HSFA and challenged with ETEC (EHSFA), 5) pigs
      with ESFA and supplemented with a cocktail of E. coli probiotics (PSFA), and 6)
      pigs with EHSFA and supplemented with a cocktail of E. coli probiotics (PHSFA).
      After 4 d acclimatization, crowding stress was started on d 5, E. coli probiotics
      were given daily from d 5, and ETEC challenge was administered on d 8 and 10.
      Body weight and feed disappearance were determined weekly and severity of
      diarrhea was characterized daily. Blood samples were collected for biochemistry
      and inflammatory analysis and pigs were euthanized to obtain digesta for
      bacterial enumeration. The ADG and ADFI decreased (P < 0.05) in stressed and ETEC
      challenged pigs 5 d after ETEC challenge. The ETEC population was higher in both
      ileal and colon digesta of stressed pigs whereas ETEC-challenged and probiotic
      fed pigs had higher fecal consistency scores 96 h and 7 d after ETEC challenge.
      Stressed pigs had higher (P < 0.001) levels of neutrophils, neutrophil:lymphocyte
      ratio, albumin:globulin ratio, fibrinogen, total protein:fibrinogen ratio, and
      cortisol. Generally, the levels of cortisol, interleukin 6 (IL-6), and tumor
      necrosis factor alpha (TNF-alpha) differed over time among some treatment groups.
      In conclusion, reduced space allowance stress and ETEC challenge depressed
      certain aspects of performance and immunological responses and increased E. coli
      counts; however, probiotics feeding had little positive effects on these measures
      suggesting further research. 

PMID- 24663173
TI  - Ruminant Nutrition Symposium: Improving cell wall digestion and animal
      performance with fibrolytic enzymes.
AB  - This paper aimed to summarize published responses to treatment of cattle diets
      with exogenous fibrolytic enzymes (EFE), to discuss reasons for variable EFE
      efficacy in animal trials, to recommend strategies for improving enzyme testing
      and EFE efficacy in ruminant diets, and to identify proteomic differences between
      effective and ineffective EFE. A meta-analysis of 20 dairy cow studies with 30
      experiments revealed that only a few increased lactational performance and the
      response was inconsistent. This variability is attributable to several enzyme,
      feed, animal, and management factors that were discussed in this paper. The
      variability reflects our limited understanding of the synergistic and sequential
      interactions between exogenous glycosyl hydrolases, autochthonous ruminal
      microbes, and endogenous fibrolytic enzymes that are necessary to optimize
      ruminal fiber digestion. An added complication is that many of the standard
      methods of assaying EFE activities may over- or underestimate their potential
      effects because they are based on pure substrate saccharification and do not
      simulate ruminal conditions. Our recent evaluation of 18 commercial EFE showed
      that 78 and 83% of them exhibited optimal endoglucanase and xylanase activities,
      respectively, at 50  degrees C, and 77 and 61% had optimal activities at pH 4 to
      5, respectively, indicating that most would likely act suboptimally in the rumen.
      Of the many fibrolytic activities that act synergistically to degrade forage
      fiber, the few usually assayed, typically endoglucanase and xylanase, cannot
      hydrolyze the recalcitrant phenolic acid-lignin linkages that are the main
      constraints to ruminal fiber degradation. These factors highlight the futility of
      random addition of EFE to diets. This paper discusses reasons for the variable
      animal responses to dietary addition of fibrolytic enzymes, advances explanations
      for the inconsistency, suggests a strategy to improve enzyme efficacy in ruminant
      diets, and describes differences among the proteomes of effective and ineffective
      EFE.

PMID- 24663174
TI  - Body composition and feed intake of reproducing and growing mice divergently
      selected for heat loss.
AB  - Changes in maintenance energy requirements and in feed efficiency have been
      achieved by divergent selection for heat loss in mice in 3 replicates, creating
      high heat loss, high maintenance (MH) and low heat loss, low maintenance (ML)
      lines and an unselected control (MC). However, feed intake has mainly been
      measured in mature animals and not during growth or reproduction. Additionally,
      there is evidence that reducing maintenance energy will increase fat content, an
      undesirable result. To evaluate if selection has altered body composition and
      lifecycle feed intake, mating pairs were continuously mated and maintained for up
      to 1 yr unless culled. Offspring pairs were sampled from each line at each parity
      and maintained from 21 to 49 d of age. Feed intake was recorded for mating pairs
      throughout the year and on offspring pairs. Body weight was recorded on all
      animals at culling as well as percent fat, total fat, and total lean, measured by
      dual X-ray densitometry. Average daily gain was also recorded for offspring.
      Energy partitioning was achieved using 2 approaches: Approach I regressed energy
      intake of the pair on sum of daily metabolic weight and total gain to obtain
      maintenance (bm) and growth (bg) coefficients for each line, replicate, feeding
      period, and sex (offspring pairs only); Approach II calculated bm for each pair
      assuming constant energy values for lean and fat gain. Energy coefficients and
      body composition traits were evaluated for effect of selection (MH vs. ML) and
      asymmetry of selection ([MH + ML]/2 vs. MC). Both MC mating and offspring pairs
      tended to have greater BW than the average of the selection lines (P < 0.08).
      Males of offspring pairs weighed more than females (P < 0.01), while females of
      mating pairs weighed more than males (P < 0.01). Line was insignificant (P >
      0.15) for body composition traits. Using Approach I, MH mice had a greater bm
      than ML mice for mating pairs (P = 0.03) but not offspring pairs (P = 0.50). For
      Approach II, MH had a greater bm than ML mice for both mating (P = 0.01) and
      offspring pairs (P = 0.01). The effect of selection for heat loss on body
      composition was smaller than previously reported and unlikely to outweigh the
      benefit of reduced feed intake, which was shown to be maintained throughout an
      entire lifecycle that included reproducing animals. Additionally, the reduction
      in energy intake seems primarily due to reduced maintenance energy costs,
      validating the success of the selection procedure. 

PMID- 24663175
TI  - Evaluation of Columbia, U.S. Meat Animal Research Center Composite, Suffolk, and
      Texel rams as terminal sires in an extensive rangeland production system: VI.
      Measurements of live-lamb and carcass shape and their relationship to carcass
      yield and value.
AB  - Linear measurements on live lambs and carcasses can be used to characterize sheep
      breeds and may have value for prediction of carcass yield and value. This study
      used 512 crossbred lambs produced over 3 yr by mating Columbia, U.S. Meat Animal
      Research Center (USMARC) Composite, Suffolk, and Texel rams to adult Rambouillet
      ewes to assess sire-breed differences in live-animal and carcass shape and to
      evaluate the value of shape measurements as predictors of chilled carcass weight
      (CCW), weight of high-value cuts (rack, loin, leg, and sirloin; HVW), weight of
      trimmed high-value cuts (trimmed rack and loin and trimmed, boneless leg and
      sirloin; TrHVW), and estimated carcass value before (CVal) and after trimming of
      high-value cuts (TrCVal). Lambs were produced under extensive rangeland
      conditions, weaned at an average age of 132 d, fed a concentrate diet in a
      drylot, and harvested in each year in 3 groups at target mean BW of 54, 61, and
      68 kg. Canonical discriminant analysis indicated that over 93% of variation among
      sire breeds was accounted for by the contrast between tall, long, less-thickly
      muscled breeds with greater BW and CCW (i.e., the Columbia and Suffolk) compared
      with shorter, more thickly muscled breeds with smaller BW and CCW. After
      correcting for effects of year, harvest group, sire breed, and shipping BW,
      linear measurements on live lambs contributed little to prediction of CCW.
      Similarly, after accounting for effects of CCW, linear measurements on live
      animals further reduced residual SD (RSD) of dependent variables by 0.2 to 5.7%,
      with generally positive effects of increasing live leg width and generally
      negative effects of increasing heart girth. Carcass measurements were somewhat
      more valuable as predictors of carcass merit. After fitting effects of CCW,
      additional consideration of carcass shape reduced RSD by 2.1, 3.6, 9.5, and 2.2%
      for HVW, TrHVW, CVal, and TrCVal, respectively. Effects of increasing carcass leg
      width were positive for HVW, TrHVW, and TrCVal. We also observed positive effects
      of increasing carcass length on TrCVal and negative effects of increasing cannon
      bone length on HVW and CVal. Increasing shoulder width had positive effects on
      CVal but negative effects on TrHVW. Differences in lamb and carcass shape were
      significantly associated with carcass yield and value, but the additional
      accuracy associated with use of these measurements was modest relative to that
      achieved from use of only shipping BW or CCW. 

PMID- 24663176
TI  - Interactive effects of distillers dried grains with solubles and housing system
      on reproductive performance and longevity of sows over three reproductive cycles.
AB  - An experiment was conducted to evaluate the interactive effects of dietary
      distillers dried grains with solubles (DDGS) in sow diets and housing systems on
      reproductive performance and longevity. Sows (311 for parity 0 and 90 for parity
      1) were assigned randomly within parity to 1 of 4 treatments and maintained on
      these treatments for up to 3 reproductive cycles. Sows were fed either fortified
      corn-soybean meal control diets (CON) during gestation and lactation or diets
      containing 40% DDGS in gestation and 20% DDGS in lactation and were housed either
      in individual stalls or group pens with electronic sow feeders during gestation.
      Sows fed DDGS had smaller (P < 0.05) litter size (born alive, 11.0 vs. 11.6;
      weaning, 9.8 vs. 10.2) and had more (P < 0.05) stillborns (0.9 vs. 0.7) than sows
      fed CON. Litters nursing sows fed DDGS gained less weight (P < 0.01) than litters
      nursing sows fed CON (47.8 vs. 49.8 kg, respectively). Group-housed sows tended
      to farrow smaller litters (born alive, 11.0 vs. 11.5; P < 0.10) and had fewer
      pigs at weaning (9.9 vs. 10.2; P < 0.05) compared with stall-housed sows. Litters
      from group-housed sows tended (P < 0.10) to gain less weight while suckling than
      those from stall-housed sows (48.3 vs. 49.4 kg, respectively). Diet did not
      affect the percentage of sows that completed each successive reproductive cycle.
      Stall housing tended to increase (P = 0.06) the completion rate of sows at the
      second reproductive cycle (80.0 vs. 68.2%) and increased (P < 0.05) the
      completion rate of sows in the third reproductive cycle (68.9 vs. 55.8%) compared
      with group housing. Sows fed DDGS produced fewer (P < 0.05) live-born pigs (26.2
      vs. 27.4) and tended (P < 0.10) to have fewer pigs weaned (23.7 vs. 24.5) over 3
      reproductive cycles compared with sows fed CON. Stall-housed sows farrowed more
      (P < 0.05) total pigs (30.1 vs. 26.7) and live pigs (28.4 vs. 25.2) and had more
      weaned pigs (25.2 vs. 23.1) compared with group-housed sows over 3 reproductive
      cycles. In conclusion, long-term feeding of DDGS decreased litter size and sow
      productivity but did not affect sow longevity. Long-term housing of sows in group
      pens decreased litter size, sow longevity, and sow productivity. The detrimental
      effects of housing pregnant sows in pens were most notable when sows were fed
      corn-soybean meal-based diets compared with DDGS diets. 

PMID- 24663177
TI  - Effects of gestation and lactation on forage intake, digestion, and passage rates
      of primiparous beef heifers and multiparous beef cows.
AB  - Angus-cross cows (n = 13; 8 pregnant, BW 610 +/- 24 kg, and 5 nonpregnant, BW 571
      +/- 23 kg) and heifers (n = 13; 8 pregnant, BW 511 +/- 40 kg, and 5 nonpregnant,
      BW 451 +/- 60 kg) were individually fed chopped warm-season grass hay (5.5% CP,
      67% NDF) for ad libitum intake and soybean meal (46% CP) at 450 g/d. Intake was
      measured daily, and DM digestibility, digesta passage rate, and plasma glucose
      and beta-hydroxybutyrate (BHBA) concentrations were measured every 14 d from 49 d
      prepartum to 49 d postpartum. Prepartum DMI (% of BW) increased over time for
      pregnant heifers through 2 wk prepartum before declining but did not change over
      time for pregnant cows. Dry matter digestibility decreased with advancing
      gestation (P < 0.001); pregnant animals had greater digestibility than
      nonpregnant cows and heifers (P = 0.02). Digestibility was not influenced by age
      (P = 0.99). Pregnant cows and heifers had faster digesta passage rates than their
      nonpregnant counterparts (P = 0.02). Pregnant animals had lower plasma glucose (P
      < 0.001). Plasma BHBA concentrations were greater in pregnant animals than in
      nonpregnant animals (P < 0.001) but were not influenced by age (P = 0.27) or time
      prepartum (P = 0.98). Postpartum DMI (% of BW) was greater for lactating heifers
      than other groups (age * lactation status; P = 0.05) and increased over time (P <
      0.001). Diet digestibility increased with time postpartum (P < 0.001), and
      heifers had greater digestibility than cows from 3 to 7 wk postpartum but not at
      1 wk postpartum (age * time; P = 0.02). Postpartum passage rate was not
      influenced by age or lactation status (P > 0.23). Lactating animals had lower
      plasma glucose and greater plasma BHBA concentrations postpartum than
      nonlactating animals (P < 0.001). Calves from mature cows grew faster than calves
      from heifers (age * time; P < 0.001). These data show that although primiparous
      beef heifers have similar DM digestibility, passage rates, and plasma glucose and
      BHBA concentrations, intake patterns differ between heifers and cows. Although
      DMI (% of BW) and digestibility did not differ between pregnant beef heifers and
      pregnant mature cows, the DMI (% of BW) was greater for lactating primiparous
      cows (heifers) than for lactating multiparous cows. Even with their postpartum
      increase in DMI, primiparous beef heifers were not able to consume adequate
      amounts of the warm-season forage to support their requirements for maintenance,
      growth, and lactation. 

PMID- 24663178
TI  - The combination of arginine and leucine supplementation of reduced crude protein
      diets for boars increases eating quality of pork.
AB  - Fifty-four entire male pigs (Duroc * Pietrain * Large White * Landrace) from a
      commercial crossbred operation were used to investigate the effect of dietary Arg
      supplementation, protein reduction (PR), and Leu supplementation on performance,
      carcass traits, and meat quality. Pigs weighing 58.9 +/- 1.6 kg BW were randomly
      assigned to 1 of 6 treatments (n = 9). The 6 dietary treatments were normal CP
      diet (16% CP, NPD), reduced CP diet (13% CP, RPD), reduced CP diet with Leu
      addition to 2.0% (RPDL), normal CP diet supplemented with 1% Arg (16% CP, Arg
      NPD), reduced CP diet supplemented with 1% Arg (13% CP, Arg-RPD), and reduced CP
      diet with Leu addition to 2.0% and supplemented with 1% Arg (13% CP, Arg-RPDL).
      Pigs were slaughtered at 91.7 +/- 1.6 kg BW. Dietary Arg supplementation had no
      effect on intramuscular fat (IMF) content but produced meat off-flavor and
      increased meat tenderness and overall acceptability. The PR increased (P < 0.001)
      IMF content (45% to 48%) but negatively affected the growth performance of pigs.
      In addition, PR increased (P < 0.05) back fat thickness and decreased loin
      weight. Leucine addition did not affect IMF content, back fat thickness, or loin
      weight. There was an increase of juiciness with PR and Leu addition, which
      accompanied the increase of IMF content with the low-CP diet. The PR increased
      meat deposition of 18:1c9, SFA, MUFA, and PUFA, which were not correlated with
      any pork sensory trait. The main combined effect of Arg was an increased
      tenderness and overall acceptability of pork. In conclusion, it was confirmed
      that dietary CP reduction enhances pork eating quality but negatively affects
      growth performance and carcass characteristics of pigs. 

PMID- 24663179
TI  - High dietary sulfur decreases the retention of copper, manganese, and zinc in
      steers.
AB  - To examine the effects of dietary S on diet digestibility and apparent mineral
      absorption and retention, 16 steers [8 ruminally fistulated (368 +/- 12 kg BW)
      and 8 unmodified (388 +/- 10 kg BW)] were paired within modification status and
      BW, and within each of the 2 consecutive 28-d periods, 4 pairs of steers were
      randomly assigned to either a low-S (0.24%) or high-S (0.68%) pelleted diet.
      Bromegrass hay was fed at 5 or 7% of the diet, during periods 1 and 2,
      respectively. Sodium sulfate was used to increase the S content of the high-S
      diet. The low-S steers were fed the amount of feed their high-S counterpart
      consumed the previous day, while the high-S steers received 110% of the previous
      day's intake. Steers were adapted to individual metabolism stalls for 4 d (d -3
      to 0 of period), acclimated to diet for 7 d (d 1 to 7 of period), and after high
      S steers were consuming ad libitum intake for 7 d (d 14 of period), total urine
      and feces were collected for 5 d. Feed intake and orts were recorded daily. Dry
      matter and OM digestibility were determined. Jugular blood was collected before
      and after each collection period on d 14 and 20, and liver biopsies were
      collected on d 0 and 27. Macromineral (Ca, K, Mg, and Na) and micromineral (Cu,
      Mn, and Zn) concentrations were determined for pellets and hay, orts, feces,
      urine, and plasma and liver samples from each steer via inductively coupled
      plasma spectrometry. Dry matter intake, DM and OM digestibility, and urine volume
      were not affected (P >= 0.11) by dietary treatment, but fecal output was greater
      (P = 0.02) in the low-S steers than the high-S steers. A high-S diet decreased
      plasma Cu (P = 0.04) and liver Zn (P = 0.03) compared to low-S steers. No
      differences (P >= 0.20) were noted among urinary excretion of Cu, Mn, and Zn.
      Sodium absorption was greater (P < 0.01) and Cu, Mn, and Zn retention was lesser
      (P <= 0.01) in the high-S steers than the low-S steers. Apparent absorption of
      Ca, K, and Mg was not affected (P >= 0.18) by dietary treatment, while absorption
      of Cu, Mn, and Zn in the high-S treatment was lesser (P <= 0.06). In conclusion,
      consumption of a high-S diet for 28 d had limited effects on Ca, K, Mg, and Na
      absorption and retention, but decreased Cu, Mn, and Zn retention, which may limit
      growth and production of cattle consuming a high-S diet long-term. 

PMID- 24663180
TI  - Meal frequency changes the basal and time-course profiles of plasma nutrient
      concentrations and affects feed efficiency in young growing pigs.
AB  - Ingested dietary nutrients and feed energy are partitioned among tissues to
      sustain body growth. Based on the respective costs of the various metabolic
      pathways allowing use and storage of feed energy into cells, it may be theorized
      that daily meal frequency could affect growth, body composition or feed
      efficiency. This study aimed to determine the effects of daily meal frequency on
      nutrient partitioning, tissue metabolism and composition, and performance. Young
      growing pigs (30 kg BW) were offered a same amount of feed either in 2 (M2, n =
      15) or 12 (M12, n = 16) meals per day during a 3-wk interventional period.
      Animals fed twice a day had an accelerated weight gain (+6.4%, P < 0.05) and
      exhibited a greater G:F (+4%, P = 0.03) than animals fed 12 meals per day during
      this period. Basal plasma concentrations of glucose, lactate, triglyceride, urea,
      and leptin were lower (P < 0.001) in M2 pigs than in M12 pigs. Meal frequency
      also changed (P < 0.001) the time-course profiles of plasma concentrations of
      glucose, insulin, and lactate in response to meal ingestion. A greater rise and a
      sharper fall in plasma glucose and insulin levels were observed in M2 pigs
      compared with M12 pigs. In both groups, similarities were observed in the
      postprandial time courses of plasma concentrations of insulin and of alpha-amino
      nitrogen (used as a measure of total AA). Despite these metabolic responses,
      tissue lipids, glycogen content, and enzyme activities participating in energy
      metabolism in muscle and liver were similar (P > 0.10) in both groups at the end
      of the trial. Percentage of perirenal fat in the body and depth of dorsal
      subcutaneous fat tissue were not affected by meal frequency, but kidney weight
      was lower (-18%, P < 0.001) in M2 pigs than in M12 pigs. Altogether, the less
      frequent daily meal intake improves the conversion of feed into weight gain,
      without marked modifications of tissue composition in young pigs. 

PMID- 24663181
TI  - Effect of grass hay intake on fiber digestion and digesta retention time in the
      hindgut of horses.
AB  - Eight Thoroughbred horses were used to examine the effects of grass hay intake on
      the fiber digestion and the retention time of digesta in the total
      gastrointestinal tract and the hindgut segments. The horses were randomly
      assigned to 2 groups and offered 2.0 (high intake [HI]) or 1.3 kg DM/(100 kg BW *
      d; low intake [LI]) of timothy hay in equal amounts every 3 h for 17 d. The
      digestibility and total tract mean retention time of digesta (tMRT) in the total
      gastrointestinal tract were measured from d 11 to d 15. To measure the mean
      retention time of digesta in each hindgut segment (sMRT), the horses were
      euthanized on d 17, after being fed a series of hay markers that were labeled
      with different rare earth elements. The digesta were collected from the ileum,
      cecum, right ventral colon (RVC), left ventral colon (LVC), left dorsal colon,
      right dorsal colon (RDC), and small colon (SC) to measure fiber digestibility,
      sMRT, VFA concentration, and fibrolytic activities. The digestibility of NDF and
      ADF in the total gastrointestinal tract was lower (P < 0.01) for HI than for LI.
      The cumulative disappearance of NDF and ADF from the ileum to the LVC attained
      90% of total tract digestion regardless of hay intake. Values did not differ
      according to treatments in the ileum and the cecum but were lower (P < 0.01) for
      HI than for LI in the postcecal segments. This was caused by the smaller increase
      in the cumulative NDF and ADF disappearance from the cecum to the RVC for HI than
      for LI. The solid phase tMRT was shorter (P = 0.04) for HI than for LI. Although
      sMRT in the RDC and SC were shorter (P = 0.04 and P < 0.01, respectively) for HI
      than for LI, no differences were observed in the other hindgut segments. There
      was no difference between treatments in the total VFA concentration, VFA
      proportions, or the specific activity of carboxymethyl cellulase and xylanase in
      each hindgut segment. The fibrolytic activity for the cecum and RVC were greatest
      and decreased beyond the LVC. A clear relation between mean retention time and
      fiber digestion was observed in the total gastrointestinal tract, but the
      segments where a difference in sMRT was detected because of the intake were not
      the same as those with the fiber digestibility depression. Although the reduction
      in total tract fiber digestibility with increased feed intake was clearly shown
      to occur between the cecum and RVC, which were the main segments for fiber
      digestion, it could be explained neither by the sMRT nor by the fibrolytic
      activity in these segments.

PMID- 24663182
TI  - Dietary plant extracts modulate gene expression profiles in ileal mucosa of
      weaned pigs after an Escherichia coli infection.
AB  - This study was conducted to characterize the effects of infection with a
      pathogenic F-18 Escherichia coli and 3 different plant extracts on gene
      expression of ileal mucosa in weaned pigs. Weaned pigs (total = 64, 6.3 +/- 0.2
      kg BW, and 21-d old) were housed in individual pens for 15 d, 4 d before and 11 d
      after the first inoculation (d 0). Treatments were in a 2 * 4 factorial
      arrangement: with or without an F-18 E. coli challenge and 4 diets (a nursery
      basal, control diet [CON], 10 ppm of capsicum oleoresin [CAP], garlic botanical
      [GAR], or turmeric oleoresin [TUR]). Results reported elsewhere showed that the
      plant extracts reduced diarrhea in challenged pigs. Total RNA (4 pigs/treatment)
      was extracted from ileal mucosa of pigs at d 5 post inoculation. Double-stranded
      cDNA was amplified, labeled, and further hybridized to the microarray, and data
      were analyzed in R. Differential gene expression was tested by fitting a mixed
      linear model in a 2 * 4 factorial ANOVA. Bioinformatics analysis was conducted by
      DAVID Bioinformatics Resources 6.7 (DAVID; National Institute of Allergy and
      Infectious Diseases [NIAID, NIH], http://david.abcc.ncifcrf.gov). The E. coli
      infection altered (P < 0.05) the expression of 240 genes in pigs fed the CON (148
      up- and 92 down-regulated). Compared with the infected CON, feeding CAP, GAR, or
      TUR altered (P < 0.05) the expression of 52 genes (18 up, 34 down), 117 genes (34
      up- and 83 down-regulated), or 84 genes (16 up- and 68 down-regulated),
      respectively, often counteracting the effects of E. coli. The E. coli infection
      up-regulated (P < 0.05) the expression of genes related to the activation of
      immune response and complement and coagulation cascades, but down-regulated (P <
      0.05) the expression of genes involved in protein synthesis and accumulation.
      Compared with the CON, feeding CAP and GAR increased (P < 0.05) the expression of
      genes related to integrity of membranes in infected pigs, indicating enhanced gut
      mucosa health. Moreover, feeding all 3 plant extracts reduced (P < 0.05) the
      expression of genes associated with antigen presentation or other biological
      processes of immune responses, indicating they attenuated overstimulation of
      immune responses caused by E. coli. These findings may explain why diarrhea was
      reduced and clinical immune responses were ameliorated in infected pigs fed plant
      extracts. In conclusion, plant extracts altered the expression of genes in ileal
      mucosa of E. coli-infected pigs, perhaps leading to the reduction in diarrhea
      reported previously. 

PMID- 24663183
TI  - Quantitative trait loci map for growth and morphometric traits using a channel
      catfish x blue catfish interspecific hybrid system.
AB  - Head length, head depth, head width, body depth, body width, caudal depth, and
      caudal width and total length and BW were measured for 71 backcross full sibs
      between the interspecific backcross F1 (female channel catfish [Ictalurus
      punctatus] * male blue catfish [Ictalurus furcatus]) female * blue catfish male.
      Body measurements were corrected for both size and the relationship between
      relative body shape and size, which is critical but usually ignored in fish
      research. Amplified fragment length polymorphism analysis was used for
      construction of a QTL map with 44 linkage groups. Eleven of 44 linkage groups had
      at least 1 significant QTL (P <= 0.05) and 11 of 44 at P = 0.10. Linkage group 19
      was unique as it had multiple QTL for every trait measured, except for caudal
      width for which no QTL was identified on any linkage group. Approximately half of
      the markers measured were associated with positive effects (increase in size) on
      the traits and half had negative effects (decrease in size). Linkage groups 5, 9,
      18, 20, 39, and 40 were significant for multiple traits and always had a trait
      negative effect. Total length is represented on the map by the most linkage
      groups and the most markers. The linkage relationships found among BW, total
      length, and the 7 morphometric traits indicated that multiple trait marker
      assisted selection to simultaneously increase BW body depth, body width, and
      caudal depth while decreasing the head traits with the goal to increase body
      weight and carcass yield would be very difficult. Multiple genetic enhancement
      approaches would likely be needed to simultaneously improve BW and body
      conformation. 

PMID- 24663184
TI  - Evaluation of standardized ileal digestible valine:lysine, total lysine:crude
      protein, and replacing fish meal, meat and bone meal, and poultry byproduct meal
      with crystalline amino acids on growth performance of nursery pigs from seven to
      twelve kilograms.
AB  - Five experiments were conducted to evaluate replacing fish meal, meat and bone
      meal, and poultry byproduct meal with crystalline AA for 7- to 12-kg pigs. In all
      experiments, pigs (PIC TR4 * 1050) were fed a common diet for 3 d postweaning,
      treatment diets for 14 d (d 0 to 14), and, again, a common diet for 14 d (d 14 to
      28). Treatment diets were corn-soybean meal based and formulated to contain 1.30%
      standardized ileal digestible (SID) Lys. Experiment 1 evaluated replacing dietary
      fish meal with crystalline AA. For the 6 treatments, crystalline Lys, Met, Thr,
      Trp, Ile, Val, Gln, and Gly all increased to maintain minimum AA ratios as fish
      meal decreased (4.50, 3.60, 2.70, 1.80, and 0.90 to 0.00%). There was no
      difference in ADG, ADFI, or G:F among treatments, validating a low-CP, AA
      fortified diet for subsequent experiments. Experiment 2 evaluated deleting
      crystalline AA from a low-CP, AA-fortified diet with 6 treatments: 1) a positive
      control similar to the diet validated in Exp. 1, 2) positive control with l-Ile
      deleted, 3) positive control with l-Trp deleted, 4) positive control with l-Val
      deleted, 5) positive control with l-Gln and l-Gly deleted, and 6) positive
      control with l-Ile, l-Trp, l-Val, l-Gln, and l-Gly deleted (NC). Pigs fed the
      positive control or Ile deleted diet had improved (P < 0.05) ADG and ADFI during
      d 0 to 14 compared with pigs fed diets with l-Trp or l-Val deleted or NC.
      Experiment 3 evaluated 6 treatments with total Lys:CP of 6.79, 6.92, 7.06, 7.20,
      7.35, and 7.51%. Fish meal was adjusted as a source of dispensable N to achieve
      the target Lys:CP. There were no differences in growth performance among pigs fed
      different Lys:CP diets. Experiment 4 evaluated increasing SID Val:Lys with Val at
      57.4, 59.9, 62.3, 64.7, 67.2, and 69.6% of Lys. Average daily gain and ADFI
      increased (quadratic, P < 0.01) and G:F improved (linear, P = 0.02) during d 0 to
      14 as Val:Lys increased from 57.4 to 64.7%. Experiment 5 was a 2 * 3 factorial
      arrangement of treatments with main effects of low or high level of crystalline
      AA and 3 animal protein sources (fish meal, meat and bone meal, or poultry
      byproduct meal). Low- and high-crystalline AA diets contained 4.5 or 1% fish
      meal, 6 or 1.2% meat and bone meal, and 6 or 1% poultry byproduct meal,
      respectively. No AA * protein source interactions were observed. From d 0 to 14,
      no differences in growth performance among protein sources was found, whereas
      increasing crystalline AA improved (P = 0.04) ADG. In conclusion, crystalline AA
      can replace fish meal, meat and bone meal, and poultry byproduct meal when
      balanced for SID AA ratios of Met and Cys:Lys (58%), Thr:Lys (62%), Trp:Lys
      (16.5%), Val:Lys (65%), and Ile:Lys (52%). 

PMID- 24663185
TI  - Role of U.S. animal control agencies in equine neglect, cruelty, and abandonment
      investigations.
AB  - Every state in the United States has regulations prohibiting acts of neglect and
      cruelty against animals. Local law enforcement and animal control agencies are
      responsible in many communities to enforce these statutes. As society's
      perception of horses has changed from their origin as livestock to companion
      animals in modern times, owners have transitioned their care and management. The
      goal of this study was to identify the role and capacities of local animal
      control services in the United States that investigate equine neglect, cruelty,
      and abandonment investigations and to identify challenges and outcomes of the
      investigations. A 128-question online survey was accessible for animal agencies
      to complete. Comprehensive questions included their capacity for investigating
      equine cases, funding, housing for horses, and causes and outcomes of
      investigations. Respondents also were asked to select a single case and provide
      detailed information on the condition of horses, seizure and custody procedures,
      costs, and prosecution proceedings. A total of 165 respondents from 26 states
      completed all or the majority of the questions. A total of 6,864 equine
      investigations were initiated between 2007 and 2009 by 90 agencies, which
      extrapolates to 38 investigations annually per agency. A typical agency has an
      average annual budget of $740,000, employs 7 animal control officers, and spends
      about $10,000 annually on equine cases. Neglect was ranked as the most common
      reason for investigation. Owner ignorance, economic hardship, and lack of
      responsibility were the highest ranked causes of neglect and cruelty. Individual
      cases were provided by 91 agencies concerning 749 equines. The physical condition
      of the horse was the primary factor of investigation, and low body condition,
      parasite infestation, and compromised dental condition were present in most
      seized horses. Over half of the equine owners previously had been investigated or
      charged with neglect or cruelty of animals or were identified with cruelty or
      abuse offenses to people. Less than 3% of the cases advanced to adjudication, and
      these were likely to be decided by a judge rather than a jury. Judgments of
      guilty verdicts and pleas were 9 times more common than acquittal. Challenges for
      equine investigations cases included lack of funding, limited availability of
      facilities for horses, and providing educational materials for horse owners to
      aid in prevention and resolution of neglect cases. 

PMID- 24663186
TI  - Numerical analysis of intensity signals resulting from genotyping pooled DNA
      samples in beef cattle and broiler chicken.
AB  - Pooled genomic DNA has been proposed as a cost-effective approach in genomewide
      association studies (GWAS). However, algorithms for genotype calling of biallelic
      SNP are not adequate with pooled DNA samples because they assume the presence of
      2 fluorescent signals, 1 for each allele, and operate under the expectation that
      at most 2 copies of the variant allele can be found for any given SNP and DNA
      sample. We adapt analytical methodology from 2-channel gene expression microarray
      technology to SNP genotyping of pooled DNA samples. Using 5 datasets from beef
      cattle and broiler chicken of varying degrees of complexity in terms of design
      and phenotype, continuous and dichotomous, we show that both differential
      hybridization (M = green minus red intensity signal) and abundance (A = average
      of red and green intensities) provide useful information in the prediction of SNP
      allele frequencies. This is predominantly true when making inference about
      extreme SNP that are either nearly fixed or highly polymorphic. We propose the
      use of model-based clustering via mixtures of bivariate normal distributions as
      an optimal framework to capture the relationship between hybridization intensity
      and allele frequency from pooled DNA samples. The range of M and A values
      observed here are in agreement with those reported within the context of gene
      expression microarray and also with those from SNP array data within the context
      of analytical methodology for the identification of copy number variants. In
      particular, we confirm that highly polymorphic SNP yield a strong signal from
      both channels (red and green) while lowly or nonpolymorphic SNP yield a strong
      signal from 1 channel only. We further confirm that when the SNP allele
      frequencies are known, either because the individuals in the pools or from a
      closely related population are themselves genotyped, a multiple regression model
      with linear and quadratic components can be developed with high prediction
      accuracy. We conclude that when these approaches are applied to the estimation of
      allele frequencies, the resulting estimates allow for the development of cost
      effective and reliable GWAS. 

PMID- 24663187
TI  - Impact of reference population on accuracy of imputation from 6K to 50K single
      nucleotide polymorphism chips in purebred and crossbreed beef cattle.
AB  - Genotyping with lower density but lower cost panels enables more animals to be
      genotyped for genomic selection. Imputation enables the determination of missing
      SNP genotypes in animals genotyped with a low-density panel by using information
      from a reference population genotyped with a higher density panel, which should
      increase accuracy of genomic EBV. In this study, population imputation, using
      linkage disequilibrium among markers, was implemented using the software BEAGLE,
      FIMPUTE 2.2, and IMPUTE2 in a multibreed, crossbred taurine beef cattle
      population genotyped with the Illumina SNP50. Different combinations of reference
      populations and imputed animals were defined based on breed composition. Number
      of animals (n = 250 to 4,932) and the presence of closer relatives in the
      reference population (only for Angus animals) were investigated. The overall
      average imputation accuracy for purebred animals ranged from 94.20 to 97.93%
      using FIMPUTE, from 95.35 to 98.31% using IMPUTE2, and from 90.02 to 96.38% when
      BEAGLE software was used. Imputation accuracy of crossbred animals ranged from
      54.15 to 97.53% (FIMPUTE), from 57.04 to 97.46% (IMPUTE2), and from 54.35 to
      95.64% (BEAGLE). Higher imputation accuracies were obtained when closer relatives
      along with the breed composition of imputed animals was well represented in the
      reference population. Within breed imputation from 6K to 50K did not improve when
      an additional purebred population was added to the reference population. FIMPUTE
      reduced the run time by 13 to 52 times compared to BEAGLE and 51 to 108 times
      compared to IMPUTE2. 

PMID- 24663189
TI  - Lactation estrus induction in multi- and primiparous sows in an Australian
      commercial pork production system.
AB  - This study evaluated the effect of full physical boar exposure and split weaning
      on the incidence of lactation estrus within a large commercial piggery. A total
      of 299 multiparous (MP; parity 2.5 +/- 0.03) and 303 primiparous (PP) sows of
      Large White * Duroc * Landrace genetics were individually housed in conventional
      farrowing crates from 1 wk before expected farrowing until weaning on Day 30.7 +/
      0.05 postparturition. Before shed entry, sows were allocated randomly within
      parity to receive either boar exposure (BE; n = 454) or no BE (No BE; n = 149).
      Sows assigned to receive BE were then allocated to 1 of 2 litter size treatments:
      litter size unchanged (BE; n = 302) or BE and the litter permanently reduced
      (split weaned) to 7 piglets (BESPW7; n = 152) on Day 18 of lactation. From Day 18
      of lactation until weaning, sows in both BE treatments were taken daily to a
      detection mating area where they received 15 min of full physical BE and were
      artificially inseminated at the first observed estrus. Providing sows with BE
      increased the incidence of lactation estrus, with a further increase observed
      when litter size was reduced to 7 piglets (16% No BE vs. 62% BE and 75% BESPW7; P
      < 0.05). Multiparous sows exhibited a greater incidence of lactation estrus than
      PP sows irrespective of treatment (81 compared to 52%, respectively; P < 0.05).
      Both MP and PP sows exhibited an increased incidence of lactation estrus when a
      portion of the litter was removed (MP: 76 vs. 89% and PP: 47 vs. 61%; P < 0.05).
      Farrowing rates were higher in BE MP sows mated postweaning and all BESPW7 sows
      mated postweaning when compared to their counterparts mated in lactation (P <
      0.05). Percentage live weight loss over the course of lactation was greatest for
      sows in the No BE compared to the BE and BESPW7 treatments (7.7% +/- 0.5 vs. 5.4%
      +/- 0.3 and 4.5% +/- 0.4, respectively; P < 0.05). Between Day 17 and weaning,
      piglets suckling sows in the BESPW7 treatment had a higher average weight gain
      than piglets suckling sows with a full litter (3.5 +/- 0.06 vs. 3.1 +/- 0.05 kg;
      P < 0.05). In conclusion these data suggest that providing MP sows with BE is
      effective at stimulating a synchronous lactation estrus while PP sows require, in
      addition to BE, a reduction in suckled litter size to 7 piglets. 

PMID- 24663190
TI  - Determining the influence of dietary roughage concentration and source on ruminal
      parameters related to sulfur toxicity.
AB  - Cattle feedlot diets often include ethanol coproducts that provide excess dietary
      sulfate, which is reduced to sulfide by ruminal bacteria and can be converted to
      hydrogen sulfide, which has been correlated to S toxicity. The objective of this
      study was to determine the impact of feeding varying concentrations of NDF from
      chopped cornstalks (CS) or chopped bromegrass hay (BH) on ruminal pH, ruminal H2S
      concentration, and DMI of steers fed a high-S finishing diet. Five ruminally
      fistulated steers (595 +/- 87 kg BW) were used in a 6 * 6 Latin square with 14-d
      periods and fed diets containing 0.45% S from a mixture of dried distillers
      grains and condensed corn distillers solubles. The study was a 2 * 3 factorial
      arrangement of treatments with 2 roughage sources--CS or BH--and 3 concentrations
      of added roughage NDF (rNDF)--4, 7, or 10%. Steers had individual ad libitum
      access to feed and adapted to each diet for the first 7 d of each period.
      Effective NDF linearly increased (P < 0.01) as rNDF increased and did not differ
      between sources (P = 0.44). There was no effect of concentration or source of
      rNDF on DMI (P >= 0.69). Steer behavior was observed on d 13 of each period for 3
      h postfeeding. Source of rNDF did not affect time at bunk, DMI during
      observation, or rate of DMI (P >= 0.42). Time at bunk linearly increased as rNDF
      increased (P = 0.01), while rate of DMI linearly decreased (P = 0.02). Area under
      the curve for ruminal pH of 5.4, 5.6, and 5.8, calculated using data from d 8 to
      14 via an indwelling ruminal bolus, were linearly decreased (P <= 0.03) as rNDF
      increased. Manual ruminal pH taken 6 h postfeeding on d 14 of each period did not
      differ by source (P = 0.12) but linearly increased (P < 0.01) as rNDF increased.
      Ruminal H2S concentrations measured 6 h postfeeding on d 14 of each period did
      not differ by source (P = 0.47) but linearly decreased (P < 0.01) as rNDF
      increased (0.62, 0.35, 0.31 g/m(3) for 4, 7, and 10% rNDF, respectively). A
      segmented linear model was found to best fit the ruminal pH and H2S relationship
      data, suggesting that at or below a pH of 5.6 +/- 0.08 with 95% confidence
      intervals of 5.4 and 5.8, pH is a strong predictor of H2S (P <= 0.05), while
      above this pH range H2S concentrations are not well correlated with ruminal pH (P
      > 0.50). In conclusion, adding at least 7% NDF from CS or BH to high-S feedlot
      cattle diets will increase ruminal pH and decrease H2S concentrations, thus
      decreasing potential for S toxicity.

PMID- 24663191
TI  - Estimation of body weight and development of a body weight score for adult equids
      using morphometric measurements.
AB  - Excessive BW has become a major health issue in the equine (Equus caballus)
      industry. The objectives were to determine if the addition of neck circumference
      and height improved existing BW estimation equations, to develop an equation for
      estimation of ideal BW, and to develop a method for assessing the likelihood of
      being overweight in adult equids. Six hundred and twenty-nine adult horses and
      ponies who met the following criteria were measured and weighed at 2 horse shows
      in September 2011 in Minnesota: age >= 3 yr, height >= 112 cm, and nonpregnant.
      Personnel assessed BCS on a scale of 1 to 9 and measured wither height at the
      third thoracic vertebra, body length from the point of shoulder to the point of
      the buttock, neck and girth circumference, and weight using a portable livestock
      scale. Individuals were grouped into breed types on the basis of existing
      knowledge and were confirmed with multivariate ANOVA analysis of morphometric
      measurements. Equations for estimated and ideal BW were developed using linear
      regression modeling. For estimated BW, the model was fit using all individuals
      and all morphometric measurements. For ideal BW, the model was fit using
      individuals with a BCS of 5; breed type, height, and body length were considered
      as these measurements are not affected by adiposity. A BW score to assess the
      likelihood of being overweight was developed by fitting a proportional odds
      logistic regression model on BCS using the difference between ideal and estimated
      BW, the neck to height ratio, and the girth to height ratio as predictors; this
      score was then standardized using the data from individuals with a BCS of 5.
      Breed types included Arabian, stock, and pony. Mean (+/- SD) BCS was 5.6 +/- 0.9.
      BW (kg) was estimated by taking [girth (cm)(1.48)6 * length (cm)(0.554) * height
      (cm)(0.599) * neck (cm)(0.173)]/3,596, 3,606, and 3,441 for Arabians, ponies, and
      stock horses, respectively (R(2) = 0.92; mean-squared error (MSE) = 22 kg). Ideal
      BW (kg) was estimated by taking [length (cm) * 2.8] + [height (cm) * 4.2] - 611,
      606, and 577 for Arabians, ponies, and stock horses, respectively (R(2) = 0.86;
      MSE = 24). Equids with a BCS of >= 7 had a greater likelihood of being
      overweight, and the model suggested cutoffs at the 48th and 83rd percentiles for
      underweight and overweight individuals, respectively. Morphometric measurements
      were successfully used to develop equid BW-related equations.

PMID- 24663192
TI  - Effect of Propionibacterium spp. on ruminal fermentation, nutrient digestibility,
      and methane emissions in beef heifers fed a high-forage diet.
AB  - The objective of this study was to test the efficacy of different
      Propionibacterium strains in mitigating methane (CH4) emissions in beef heifers
      fed a high-forage diet. Twenty ruminally cannulated beef heifers were used in a
      randomized block design with 28-d periods. Treatments included 1) Control, 2)
      Propionibacterium acidipropionici strain P169, 3) Propionibacterium
      acidipropionici strain P5, and 4) Propionibacterium jensenii strain P54. Strains
      (5 * 10(9) CFU) were administered daily directly into the rumen in 10 g of a
      maltodextrin carrier in a gel capsule. Control heifers received the carrier only.
      All heifers were fed a basal diet (70:30 forage to concentrate, DM basis) based
      on barley silage and corn grain. No treatment effects were observed for overall
      DMI (P = 0.78) or DMI in chambers (P = 0.29). Dry matter intake was 12 to 29%
      less in the chambers, with intake depression numerically lower in heifers
      receiving Propionibacterium than Control. Mean ruminal pH averaged 6.47 and was
      not affected by treatments (P = 0.34). Likewise, no treatment differences were
      observed for ruminal concentrations of total VFA (P = 0.24) and ammonia-N (P =
      0.49) or for molar proportion of individual VFA. Total daily enteric CH4
      production was not affected by Propionibacterium strains as compared to Control
      and averaged 178 g/d (P = 0.69). However, enteric CH4 emission intensity (g
      CH4/kg of DMI) was reduced by 12, 8, and 13% with P169, P5, and P54 as compared
      to Control, respectively (P = 0.03). No treatment effects were observed for total
      tract digestibility of nutrients. Likewise, total universal bacterial (P = 0.22)
      and methanogen (P = 0.64) counts were similar among treatments. However, the
      relative abundance of total Propionibacteria tended to increase with inoculation
      as compared to Control (P = 0.06). The relative abundance of Propionibacterium
      P169 tended to be greater at 3 h postdosing, but returned to pretreatment (0 h)
      levels within 9 h, suggesting it failed to persist at detectable levels in the
      rumen. In conclusion, Propionibacterium spp. did not reduce total enteric CH4
      production, possibly due to their inability to persist and integrate into the
      ruminal microbial community. However, CH4 emission intensity was reduced with
      Propionibacterium strains, a response attributed to the numerically greater DMI
      of heifers receiving Propionibacterium. 

PMID- 24663193
TI  - Effect of diets containing whole white lupin seeds on rabbit doe milk yield and
      milk fatty acid composition as well as the growth and health of their litters.
AB  - The effect of dietary inclusion of white lupin seed (WLS) on the milk composition
      and yield of rabbit does as well as the performance of their litters was studied.
      Two lactation diets having identical digestible protein (DP):DE ratio and two
      weaning diets having identical DP:DE ratio were formulated. The first lactation
      diet (SL) contained soybean meal (SBM; 13.0%) and sunflower meal (5.0%) as the
      main CP sources, whereas the second lactation diet (LL) was based on WLS (25.0%).
      As a result, the LL diet had a greater ether extract (EE) content than did the SL
      diet. The first weaning diet (SW) included SBM (7.0%) as the main CP source,
      whereas the second weaning diet (LW) diet was based on WLS (12.0%). No additional
      fat was added to any of the diets. A total of 32 (16 per treatment) Hyplus PS 19
      does (4,225 +/- 607 g BW, at the second parturition) were fed 1 of the 2
      lactation diets. The litters were standardized to 9 kits (564 +/- 81 g BW) on the
      day of birth and were fed 1 of the 2 weaning diets from d 17 to 69 of age. At d
      30 of age (weaning), 66 rabbits on each weaning diet (689 +/- 71 g BW; 3 per
      cage) were used to evaluate performance. Feed intake and doe BW were not affected
      by the dietary treatments. Milk yield tended to be higher between d 1 and 30 of
      lactation in does fed the LL diet (P = 0.094), a finding that is related to the
      higher dietary EE content and intake in the LL diet. When expressed per kilogram
      of metabolic weight, milk output (P < 0.05) and fat output (P < 0.05) were
      greater in these does. Improved G:F (P < 0.05) between d 1 and 21 of lactation
      and greater ADG (P = 0.072) and milk efficiency (P < 0.05) of litters was
      observed in does fed the LL diet. The milk of does fed the LL diet contained less
      linoleic acid (P < 0.05) and arachidonic acid (C 20:4n-6; P < 0.05) and more
      oleic acid (P < 0.05), alpha-linolenic acid (P < 0.05), and eicosapentaenic acid
      (P < 0.05), with a corresponding increase in the total PUFA n-3:C 20:4n-6 ratio
      (P < 0.05). The performance of fattening rabbits was not affected by dietary
      treatment. The number of ill plus dead rabbits caused by digestive disease was
      lower (P < 0.05) in rabbits fed the LW diet. Therefore, WLS is a suitable dietary
      CP source for lactating does that can replace traditionally used CP sources
      without adverse effects on feed intake and milk yield or on the growth and
      viability of their litters. Due to its fatty acid (FA) composition, the use of
      WLS in the lactation diet has the potential to improve the milk FA composition of
      does. 

PMID- 24663194
TI  - Inhibition of Escherichia coli in cultivated cattle manure.
AB  - A common practice on Israeli dairy barns comprises daily cultivation of the
      manure. Cultivation is a mechanical process used to break up and till the manure
      bedding and it results in a drier and aerated bedding and cleaner cows, which
      consequently reduces the incidence of mastitis. Cultivation was associated with a
      shorter survival of Escherichia coli in cultivated manure as compared with
      noncultivated manure. The objective of the current study was to elucidate the
      mechanism responsible for the shorter survival duration of E. coli in the
      cultivated manure. We hypothesized that microorganisms that are antagonistic to
      E. coli, developing in the cultivated manure, are responsible for this
      phenomenon. A cow manure derived E. coli strain expressing the green fluorescence
      protein and antibiotic resistance markers was used to inoculate cow manure in 1.5
      L jars. Manure treatments included cultivated and noncultivated manure. Half the
      jars of each cultivation treatment were autoclave sterilized at 121 degrees C for
      1 h on 3 successive days to eliminate from the manure antagonistic
      microorganisms. Each cultivation-sterilization treatment was performed in
      triplicate jars. Following sterilization, E. coli numbers in the cultivated and
      noncultivated manure were comparable, while in the nonsterilized manure the
      numbers were lower in the cultivated compared with the noncultivated manure.
      Several fungi isolated from the cultivated manure samples displayed inhibition
      effect on the tagged E. coli. Antagonistic fungi were also isolated from large
      scale cultivated manure samples collected on several dairy farms in Israel. These
      findings support the notion that manure cultivation might facilitate the
      development of microorganisms that are antagonistic to E. coli, thus contributing
      to the general hygiene of the cattle. Identifying the mechanisms by which the
      antagonistic fungi affect the survival of E. coli in manure could be exploited
      for improvement of the animal health and for limiting the transmission of
      zoonotic pathogens to food and water. 

PMID- 24663195
TI  - Energy requirements of Dorper crossbred ewe lambs.
AB  - The ME and NE requirements of Dorper crossbred ewe lambs grown from 35 to 50 kg
      BW were assessed in a comparative slaughter trial. Thirty-five ewe lambs (33.5 +/
      0.6 kg BW) of F1 crosses of purebred Dorper and thin-tailed Han sheep were used:
      7 lambs were slaughtered at the start of the trial to provide baseline measures
      of body composition and 7 lambs were fed ad libitum and slaughtered when they
      reached 43 kg BW to provide intermediate measures of body composition. The
      remaining 21 lambs were divided into 3 groups of 7 lambs each and fed a pelleted
      mixed diet (concentrate:roughage = 44:56, DM basis) for ad libitum intake or 65
      or 45% of ad libitum intake. All 3 groups were slaughtered when the ad libitum
      group reached 50 kg BW. Total body energy, N, fat, ash, and moisture content were
      measured. In a separate trial, 15 ewe lambs (39.5 +/- 0.7 kg BW) of F1 crosses of
      purebred Dorper and thin-tailed Han sheep were housed in metabolism cages to
      evaluate the ME value of the diet at each of the 3 levels of feed intake. In vivo
      methane production was measured by open-circuit respirometry along with the
      collection of all feces and urine. The daily NEm requirement of the ewe lambs was
      280 kJ/kg metabolic BW (BW(0.75)) or 292 kJ/kg metabolic shrunk BW (SBW(0.75)),
      whereas the daily ME requirement for maintenance was 418 kJ/kg BW(0.75) or 437
      kJ/kg SBW(0.75), with a partial efficiency of ME utilization for maintenance of
      0.67. The NEg requirement ranged from 1.37 to 3.94 MJ/d for ADG from 100 to 250 g
      BW, and the partial efficiency of ME utilization for gain was 0.44. The NE and ME
      requirements of Dorper * thin-tailed Han crossbred ewe lambs were lower than the
      recommendations of the United States' nutritional system. 

PMID- 24663196
TI  - Comparative digestibility by cattle versus sheep: effect of forage quality.
AB  - The objective was to determine the effect of forage quality on apparent total
      tract digestibility and ruminal fermentation in cattle versus sheep. Five
      yearling English crossbred (Hereford * Angus) steers (440.4 +/- 35.6 kg of
      initial BW) and 5 yearling whiteface (Rambouillet * Columbia * Debouillet)
      wethers (44.4 +/- 4.6 kg of initial BW), each fitted with a ruminal cannula, were
      randomly assigned to 1 of 3 forage sources within ruminant specie, and the study
      was conducted over 3 periods. For forage source, both animal and period served as
      the blocking factor with all forage sources represented once within each animal
      and all forage sources represented at least once within each period. The
      treatment structure was arranged in a 2 * 3 factorial with ruminant species (2)
      and forage source (3) as the factors. Forage sources were 1) alfalfa hay
      (Medicago sativa; 17.5% CP and 34.1% NDF, DM basis), 2) warm-season grass hay mix
      (Bothriochloa ischaemum and Cynodon dactylon; 7.3% CP and 74.7% NDF, DM basis),
      and 3) lovegrass hay (Eragrostis curvula; 2.5% CP and 81.9% NDF, DM basis). As a
      percent of BW, steers and wethers consumed similar (P <= 0.06) amounts of forage,
      and intake was more influenced by forage quality (P < 0.001) than ruminant
      species (P = 0.35). When expressed per unit of metabolic BW, cattle consumed more
      (P < 0.001) DM, NDF, and N than sheep. Apparent total tract digestibility was
      similar among steers and wethers when alfalfa or grass hay was fed, but decreased
      to a greater extent in wethers when low-quality lovegrass hay was fed (ruminant
      species * diet interaction, P <= 0.01). Rate (%/h) of ruminal NDF disappearance
      was greater (P = 0.02) for alfalfa and grass hay than lovegrass, but was not
      influenced (P = 0.12) by ruminant species. In addition, ruminal DM fill was
      influenced more (P < 0.01) by forage than by ruminant species (P = 0.07). Steers
      and wethers had greater (P < 0.01) DM fill from grass hay and lovegrass hay than
      alfalfa before and 5 h after feeding. Ruminal VFA were generally not influenced
      (P >= 0.06) by ruminant specie. Results suggest that apparent total tract
      digestibilities are more similar among ruminant species when moderate- to high
      quality forages are evaluated. However, sheep are not an adequate model for
      cattle when low-quality forages are compared because cattle digest low-quality
      forages to a greater extent than sheep. Expressing digestibility as digestible
      intake per unit of BW allows for a wider range of forage qualities to be compared
      when substituting sheep for cattle. 

PMID- 24663197
TI  - Effects of dietary supplementation of multi-enzyme on growth performance,
      nutrient digestibility, small intestinal digestive enzyme activities, and large
      intestinal selected microbiota in weanling pigs.
AB  - Two experiments were conducted to assess the effects of dietary supplementation
      of an exogenous multi-enzyme (EME) preparation to 35- to 65-d-old piglets on
      apparent total tract digestibility (ATTD), growth performance, digestive enzyme
      activities, and selected microbial populations in feces. In Exp.1, twenty eight
      35-d-old piglets were randomly assigned to 7 dietary treatments (corn-soybean
      based diet supplemented with 0, 100, 150, 200, 250, 300, or 350 mg EME/kg) in a
      14-d digestibility study. Piglets fed the diets supplemented with EME had greater
      ATTD of DM, CP, and GE (P = 0.001, 0.005, and 0.009, respectively) than those fed
      the diet without EME supplementation, and those ATTD values increased linearly
      and quadratically (P < 0.001) as the levels of supplemented EME increased. In
      Exp. 2, two hundred 35-d-old weanling piglets were randomly allocated to 20 pens.
      The pens were then randomly assigned to 5 dietary treatments (corn-soybean based
      diet supplemented with 0, 100, 150, 250, or 350 mg EME/kg) with 4 pens per
      treatment in a 30-d feeding experiment. Piglets has ad libitum access to diets
      and water, and they were weighed at the beginning (35-d-old), middle (50-d-old),
      and end (65-d-old) of the experiment. Fecal samples were grabbed directly from
      the rectum and digesta samples from duodenum, jejunum, and ileum were taken at
      the end of the experiment for the analysis of selected bacteria populations and
      digestive-enzyme activities. The ADG and ADFI tended to be greater with the
      increasing levels of supplemented EME in both periods, whereas G:F was improved
      (P = 0.012 and 0.017) by EME in the period of 35 to 50 d of age and during the
      overall experimental period. Furthermore, inclusion of EME in diet increased the
      counts of Lactobacilli spp. and Bacillus subtilis spp., but reduced the
      populations of Salmonella spp. and Escherichia coli spp. in the feces. The EME
      supplementation also enhanced (P < 0.05) the activities of amylase, lipase, and
      protease in the small intestine. The growth performance-enhancing effects of EME
      appeared to be mediated by the age of the piglet and the dose of EME used.
      Supplementation of corn-soybean meal diets for 35- to 65-d-old piglets with EME
      has a potential to enhance gut health condition, increase nutrient digestion, and
      increase growth performance. 

PMID- 24663198
TI  - Evaluation of the Criollo breed Romosinuano as purebred and crossbred cows with
      Brahman and Angus in Florida: I. Reproduction and parturition.
AB  - The objectives of this work were to compare reproduction and parturition traits
      of the Criollo breed Romosinuano as straightbred and crossbred cows with Angus
      and Brahman, to estimate heterosis and direct and maternal genetic breed effects,
      and to describe calf loss, cow removals from the project, the occurrence of
      calving difficulty, inadequate calf vigor at birth, and udder problems by cow
      breed groups. Cows (n = 404) were born from 2002 to 2005. After their first
      exposure to bulls as young cows, in all subsequent breeding seasons crossbred
      cows were bred to bulls of the third breed, and straightbred cows were bred to
      bulls of the other two breeds. Calving records (n = 1,484) from 2005 to 2011 were
      used to create calving and weaning rate and calving interval (excluding the
      interval between 2 and 3 yr of age). Final models for these traits included sire
      breed-dam breed interaction, cow age within year, and random animal effects.
      Heterosis estimates for Romosinuano-Brahman calving and weaning rate were 0.06 +/
      0.02 and 0.07 +/- 0.03 (P < 0.05); those for Brahman-Angus were twice as large
      (0.13 +/- 0.03 and 0.14 +/- 0.03, respectively; P < 0.001). Estimates of Brahman
      direct effects on calving and weaning rate were -0.12 +/- 0.04 and -0.14 +/- 0.05
      (P < 0.05); however, Angus direct effects were beneficial for both traits (0.1 +/
      0.05, P < 0.05). The effect of heterosis was to reduce calving interval by -49.2
      +/- 9.9 and -37.2 +/- 9.7 d for Romosinuano-Brahman and Brahman-Angus,
      respectively (P < 0.001). Romosinuano and F1 cows sired by Romosinuano and out of
      Angus dams had the most occurrences of difficult births as a proportion of cows
      that calved (0.028 and 0.025, P = 0.04). Angus-sired crossbred cows and Brahman
      cows had the most occurrences of udder problems as a proportion of lactating cows
      (0.14 to 0.21, P < 0.04). There were more Brahman-sired cows that died or were
      culled as a proportion of those cows that began the project (0.1 to 0.28, P <
      0.02) than cows in the other breed groups. Romosinuano-Brahman and Romosinuano
      Angus cow performance was acceptable, but for most traits, those pairs of breeds
      had lower heterosis than Brahman-Angus. 

PMID- 24663199
TI  - Effects of early vaccination with a gonadotropin releasing factor analog
      diphtheria toxoid conjugate on boar taint and growth performance of male pigs.
AB  - The aim of this study was to evaluate safety (in terms of detecting possible
      adverse clinical effects attributable to vaccination), efficacy, and effects on
      growth performance of a gonadotropin releasing factor analog-diphtheria toxoid
      conjugate (commercially distributed as Improvac; Zoetis, Zaventem, Belgium) in
      male pigs raised in a commercial Greek farm. A total of 1,230 male pigs was
      enrolled in 16 weekly batches and allocated to 3 groups: barrows (castrated on
      the next day after birth [study Day 0]), pigs vaccinated with the above-mentioned
      product, and intact boars. Vaccinated pigs were injected subcutaneously with 2 mL
      of the anti-gonadotropin releasing factor (GnRF) vaccine at 9 to 11 wk of age (60
      78 d) and 15 to 17 wk of age (102-120 d) and slaughtered at 22 to 25 wk of age
      (152-176 d). No clinical abnormalities or adverse events attributable to
      vaccination occurred. Mean BW of vaccinated pigs was 6% greater compared with
      barrows at slaughter (P < 0.0001). The vaccinated pigs had greater ADG than
      barrows from castration to slaughter (8%). In detail, a lower ADG from first to
      second vaccination (-12%; P < 0.0001) and a 27% greater ADG from second
      vaccination to slaughter (P < 0.0001) were observed. The ADG of vaccinated pigs
      and intact boars was not significantly different throughout the study, except
      from first to second vaccination (boars greater; P = 0.0059) and second
      vaccination to slaughter (vaccinates greater; P = 0.0390). Feed conversion ratio
      of barrows was 11 and 8% greater compared with vaccinated pigs (P = 0.0005) and
      boars (P = 0.0062) from first to second vaccination but was 23 to 26% lower
      compared with vaccinated pigs (P < 0.0001) and intact boars (P < 0.0001) from
      first vaccination to slaughter and 7 to 9.5% lower from the second vaccination to
      slaughter (P = 0.0029 and P = 0.0003 for vaccinates and intact boars,
      respectively). At slaughter, the belly fat androstenone concentration of all
      vaccinated pigs and 64% of intact boars was below 200 ng/g. Belly fat skatole
      concentration was below 20 ng/g in samples from all groups. In conclusion,
      vaccination against GnRF using the GnRF analog-diphtheria toxoid conjugate tested
      did not induce adverse clinical effects, proved effective, and compared with
      physical castration, resulted in greater BW at slaughter and improved ADG and
      feed conversion ratio from first vaccination to slaughter. 

PMID- 24663200
TI  - Encapsulated nitrate and cashew nut shell liquid on blood and rumen constituents,
      methane emission, and growth performance of lambs.
AB  - Nitrate can be a source of NPN for microbial growth at the same time that it
      reduces ruminal methane production. The objective of this study was to evaluate
      the effects of 2 encapsulated nitrate products used as urea replacers on blood
      and rumen constituents, methane emission, and growth performance of lambs.
      Eighteen Santa Ines male lambs (27 +/- 4.9 kg) were individually allotted to
      indoor pens and assigned to a randomized complete block design with 6 blocks and
      3 dietary treatments: control (CTL) = 1.5% urea, ENP = 4.51% encapsulated nitrate
      product (60.83% NO3(-) in the product DM), and ENP+CNSL = 4.51% ENP containing
      cashew nut shell liquid (60.83% NO3(-) and 2.96% cashew nut shell liquid [CNSL]
      in the product DM). Diets were isonitrogenous with 60:40 concentrate:forage
      (Tifton 85 hay) ratio. The experiment lasted for 92 d and consisted of 28 d for
      adaptation (a weekly 33% stepwise replacement of CTL concentrate by nitrate
      containing concentrates) and 64 d for data collection. The ENP and ENP+CNSL
      showed greater (P < 0.05) red blood cell counts than CTL. Blood methemoglobin
      (MetHb) did not differ (P > 0.05) among treatments, with mean values within
      normal range and remaining below 1.1% of total hemoglobin. There was an increase
      (P < 0.05) in total short-chain fatty acids concentration at 3 h postfeeding for
      ENP, with an additional increase (P < 0.05) observed for ENP+CNSL. No treatment
      effects (P > 0.05) were observed on acetate to propionate ratio. Methane
      production (L/kg DMI) was reduced (P < 0.05) with nitrate inclusion, recording
      28.6, 19.1, and 19.5 L/kg DMI for CTL, ENP, and ENP+CNSL, respectively. Addition
      of CNSL did not result (P > 0.05) in further reduction of methane production when
      compared with ENP. Final BW, DMI, ADG, and feed efficiency were similar (P >
      0.05) among treatments. Values for DMI were 1.11, 1.03, and 1.04 kg/d and for ADG
      were 174, 154, and 158 g for CTL, ENP, and ENP+CNSL, respectively. In conclusion,
      encapsulated nitrate products showed no risks of toxicity based on MetHb
      formation. The products persistently reduced methane production without affecting
      performance. Inclusion of cashew nut shell liquid in the product formulation had
      no additional benefits on methane mitigation. 

PMID- 24663201
TI  - An estimation of the protein requirements of Iberian x Duroc 50:50 crossbred
      growing pigs.
AB  - The effects of dietary protein content on the rates of gain and protein
      deposition were studied in Iberian (IB) * Duroc (DU) 50:50 barrows at 2 stages of
      growth [10.6 +/- 0.2 (n = 28) and 60.0 +/- 0.4 (n = 24) kg initial BW]. Two
      feeding, digestibility, and N-balance trials were performed. At each stage of
      growth, they were allocated in individual pens and given restrictedly (at 0.9 *
      ad libitum intake) one of 4 pelleted diets of similar energy concentration (13.8
      to 14.5 MJ ME/kg DM), formulated to provide 4 different (ideal) CP contents (236,
      223, 208, and 184 g CP/kg DM in the first trial, and 204, 180, 143, and 114 g
      CP/kg DM in the second trial). Feed allowance was offered in 2 daily equal meals.
      The average concentration of Lys was 6.59 +/- 0.13 g /100 g CP for all diets.
      Whatever the stage of growth, average daily BW gain and gain to feed ratio were
      unchanged by increases in dietary CP content (477 +/- 7 and 1,088 +/- 20 g, and
      0.475 +/- 0.027 and 0.340 +/- 0.113, respectively, in the first and second
      trial). In pigs growing from 10 to 27 kg BW, the average rate of N retention
      increased linearly (P < 0.01) on increasing the protein content in the diet up to
      a break point, so a linear-plateau dose response was observed. Pigs fed diets
      providing 208 to 236 g/kg DM did not differ in rate of protein deposition (PD). A
      maximum value of 87 (13.93 g N retained * 6.25) g PD/d was obtained when the diet
      supplied at least 208 g CP/kg DM. The broken-line regression analysis estimated
      dietary CP requirements at 211 g ideal CP (15.2 g total Lys)/kg DM. In the
      fattening pigs, there was a quadratic response (P < 0.01) in the rate of N
      retention as dietary CP content increased. Maximum N retention (18.7 g/d) was
      estimated from the first derivative of the function that relates the observed N
      retained (g/d) and dietary CP content (g/kg DM). This maximum value would be
      obtained by feeding a diet containing 185 g ideal CP (13.3 g total Lys)/kg DM and
      represents the maximum capacity of the IB * DU 50:50 pigs for protein accretion
      (i.e., 117 g PD/d). Consequently, cross breeding of IB dams with Duroc sires
      alters the metabolic response to dietary CP supply by increasing the potential of
      the crossbred to accrete protein and by modifying the pattern of PD response with
      BW. 

PMID- 24663203
TI  - Feed intake of sheep when allowed ad libitum access to feed in methane
      respiration chambers.
AB  - The patterns of feed intake when animals are allowed ad libitum access to feed in
      a respiration chamber is not known, nor are the potential effects of the
      artificial environment of chambers on voluntary feed intake. The objectives of
      the study were to describe the pattern of hourly feed intake of sheep when fed
      for ad libitum intake in respiration chambers and determine the repeatability of
      this pattern and the correlation between feed intake and methane production
      calculated at hourly intervals. Daily and hourly measurements of methane
      production and feed intake of 47 Merino wethers were measured in respiration
      chambers twice, 4 wk apart. We found that hourly feed intake of sheep with ad
      libitum access to feed in respiration chambers showed a repeatable pattern over
      the 2 measurement periods (r = 0.89, P < 0.001). During both measurements, sheep
      ate continuously throughout the 23 h period, but most of the eating occurred
      during the first 8 h in the respiration chambers. There was a significant linear
      correlation (r = 0.22) between hourly feed intake and hourly methane production
      (P < 0.001). An unexpected result from this study was that despite using an
      accepted and published acclimatization procedure to habituate the animals to the
      respiration chambers, sheep had 15 to 25% lower feed intake in the respiration
      chambers compared with their feed intake during the previous week in the animal
      house pens. In addition, daily feed intake in the respiration chamber was not
      correlated with feed intake in any of the 7 d before entering the chamber (P >
      0.05). Future methane research may consider using feed intake and changes in
      intake levels as a quantitative indicator of habituation to the methane
      measurement procedure and environment, which, given the tight association between
      feed intake and methane production, will be crucial in providing accurate values
      for methane production. 

PMID- 24663202
TI  - Effect of protein supplementation on tropical grass hay utilization by beef
      steers drinking saline water.
AB  - An experiment was conducted to assess the impact of increasing levels of
      supplemental soybean meal (SBM; 45.7% CP) in cattle consuming tropical grass hay
      (Panicum maximum cultivar Gatton; 7.0% CP and 81.8% NDF) and drinking low salt
      water (LS) or high salt water (HS). Six ruminally fistulated beef steers (BW =
      375 +/- 43 kg) were used in a 6-treatment, 4-period crossover experiment.
      Treatments were arranged as a 2 * 3 factorial, with 2 levels salt in the water
      (LS and HS: 786 and 6,473 mg/kg of total dissolved solids [TDS], respectively)
      and 3 levels of SBM (0, 0.2, and 0.4% BW/d). After 15 d of adaptation to
      treatments, periods consisted of 5 d for intake and digestibility determination,
      1 d for monitoring ruminal fermentation, 1 d for ruminal evacuation, and 1 d for
      blood sampling. Supplemental SBM * water quality interactions were significant (P
      < 0.05) for most measures of intake, except for total tract digestible OM intake
      (P = 0.38) and total tract digestible NDF intake (TTDNDFI; P = 0.32). At greater
      levels of SBM, forage OM intake, NDF intake, and water intake seemed to reach a
      plateau in LS while this was not observed in HS. Total tract digestible OM intake
      increased linearly (P = 0.01) and TTDNDFI tended to increase (P = 0.09) in
      response to increased SBM. Digestibility of OM and NDF were not affected by
      treatment (P > 0.21). Passage rate of acid detergent insoluble ash linearly
      increased (P < 0.01) in response to SBM, although it was not affected by water
      quality (P = 0.98). Total VFA concentrations and ruminal pH were not affected (P
      > 0.60 and P > 0.31, respectively) by treatment. Ruminal ammonia N levels were
      linearly increased by SBM supplementation (P < 0.01) but were not affected by
      water quality (P = 0.25). However, ruminal ammonia tended (P = 0.09) to be
      greater in HS at 0.2% of SBM supplementation. No interaction was observed for
      plasma urea N (PUN; P = 0.20). Plasma urea N was affected by SBM supplementation
      (P = 0.05) and water quality (P < 0.01). However, PUN did not differ for 0.4% SBM
      supplementation (P = 0.30) either at LS or HS treatments. In conclusion, a high
      level of SBM supplementation (0.4% BW) counteracted the detrimental effect of
      high TDS in drinking water on low-quality forage consumption by cattle. 

PMID- 24663204
TI  - Validation of national genetic evaluations for maternal beef cattle traits using
      Irish field data.
AB  - Genetic evaluations provide information to aid in breeding decisions that
      increase long-term performance of animals and herds. However, to date no study
      has been undertaken to investigate the accuracy of the Irish maternal genetic
      evaluations in beef cattle. The objective, therefore, of this study was to
      quantify the relationship between phenotypic performance and measures of genetic
      merit for predominantly maternal-related traits in Irish beef cattle. The
      association between animal EBV for calving interval, age at first calving, and
      both direct and maternal weaning weight with the respective phenotypic
      performance was quantified using a fixed effects model; the expectation for the
      regression coefficient of phenotypic performance on EBV was one. The association
      between genetic merit for cow survival, perinatal mortality, calving assistance,
      and calving dystocia with the log of the odds of the respective trait was
      quantified using logistic regression. The association analyses were conducted
      using field data on up to 38,619 records from 5,236 herds. Age at first calving
      increased linearly by 0.32 +/- 0.15 (P = 0.03) days per day increase in EBV for
      age at first calving. Calving interval increased by, on average, 0.58 +/- 0.16 (P
      = 0.002) days per day increase in EBV for calving interval although the
      association differed by parity with a greater association in pluriparae. Weaning
      weight increased linearly by 1.74 +/- 0.09 and 0.84 +/- 0.16 kg (P < 0.001) per
      kilogram increase in EBV for direct and maternal weaning weight, respectively.
      The log of the odds of a cow surviving to next lactation increased linearly by
      0.16 +/- 0.03 (P < 0.001) per unit increase in EBV for cow survival. The log of
      the odds of an assisted calving or dystocia both increased linearly by 0.21 +/-
      0.01 and 0.24 +/- 0.01, respectively, per unit increase in EBV for direct calving
      difficulty (P < 0.001). The log of the odds of a dead calf at birth increased
      linearly by 0.93 +/- 0.13 (P < 0.001) per unit increase in EBV for calf
      mortality. Results from this study show that selection of breeding animals for
      favorable maternal genetic attributes will result in favorable improvements in
      performance and profitability. 

PMID- 24663206
TI  - Glucagon-like peptide 2 treatment may improve intestinal adaptation during
      weaning.
AB  - Transition from sow's milk to solid feed is associated with intestinal atrophy
      and diarrhea. We hypothesized that the intestinotrophic hormone glucagon-like
      peptide 2 (GLP-2) would induce a dose- and health status-dependent effect on gut
      adaptation. In Exp. 1, weaned pigs (average BW at weaning 4.98 +/- 0.18 kg) were
      kept in a high-sanitary environment and injected with saline or short-acting GLP
      2 (80 MUg/(kg BW.12 h); n = 8). Under these conditions, there was no diarrhea and
      GLP-2 did not improve gastrointestinal structure or function. In Exp. 2, weaned
      pigs (average BW at weaning 6.68 +/- 0.27 kg) were kept in a low-sanitary
      environment, leading to weaning diarrhea, and injected with saline or short
      acting GLP-2 (200 ug/(kg BW.12 h); n = 11). Treatment with GLP-2 increased goblet
      cell density (P < 0.05) and reduced short chain fatty acid concentration in the
      colon (P < 0.01) but had limited effects on diarrhea. In Exp. 3, weaned pigs
      (average BW at weaning 6.90 +/- 0.32 kg) were kept in a low-sanitary environment
      and injected with saline or a long-acting acylated GLP-2 analogue (25 ug/(kg
      BW.12 h); n = 8). In this experiment, GLP-2 increased intestinal weight (+22%; P
      < 0.01) and activity of brush border enzymes (+50-100%; P < 0.05). Circulating
      GLP-2 levels were in the pharmacological range in Exp. 3 (constant levels >20,000
      pmol/L) and Exp. 2 (increases to 20,000 pmol/L for a few hours each day) while
      they were in the supraphysiological range in Exp. 1 (50-200 pmol/L). In
      conclusion, GLP-2 may improve gut structure and function in weanling pigs.
      However, the effects may be significant only under conditions of diarrhea and if
      GLP-2 exposure time is extended using long-acting analogues. 

PMID- 24663205
TI  - Behavioral and physiological responses of primiparous sows to mixing with older,
      unfamiliar sows.
AB  - Pigs are mixed into new social groups at various stages of production, and this
      study investigated the response of gilts to mixing with older unfamiliar sows.
      Four groups of 6 gilts and 1 group of 5 gilts were housed in stable groups until
      the most recently bred female reached d 39 of gestation. Then, stable groups were
      split such that 15 gilts remained in their home pens (CON) and 14 gilts were
      mixed (MIX) with 3 multiparous sows for 1 wk (M1), returned to the home pen for 1
      wk, and then mixed with 3 different sows for 1 wk (M2). Continuous behavioral
      observations of gilt location in the pen, posture, aggressive, and other social
      interactions were made from the start of M1 and M2 for 5 h. Five-minute scans of
      location, posture, and behavior as well as salivary cortisol measurements were
      taken before, during, and after each mix week, whereas skin lesions were counted
      before and after each mix. During the mixed period, MIX gilts spent more (P <=
      0.009) time in the individual feeding stalls, ventral lying, sitting, involved in
      aggression, and idle and less (P < 0.001) time in the straw-bedded area, lateral
      lying, and performing exploratory behavior (chewing, nosing, and rooting) than
      CON gilts. Additionally, MIX gilts had greater (P < 0.001) salivary cortisol
      concentrations and accumulated more (P < 0.001) skin lesions during mixing
      sessions compared to CON gilts. Mixed gilts in M2 spent more (P <= 0.013) time in
      the feeding stalls and ventral lying and less (P <= 0.029) time standing and in
      the dunging passageway compared to M1. Compared to M1, gilts had lower (P <
      0.001) salivary cortisol concentrations and fewer (P <= 0.027) lesions in front
      and middle regions of the body during M2. During M2, salivary cortisol
      concentration was positively correlated with time spent in the dunging passageway
      (Spearman's rank correlation [rs] = 0.650, P = 0.022) and negatively correlated
      with time spent in the feeding stalls (rs = -0.762, P = 0.004). Results indicated
      that gilts adapted their behavior during M2 by using the feeding stalls more, and
      they became less active, especially when interacting with the sows. Despite this
      adaptation in M2, lesions and salivary cortisol in M IX gilts were much greater
      than in CON gilts, highlighting the severity of mixing gilts with multiparous
      sows.

PMID- 24663207
TI  - F4-related mutation and expression analysis of the aminopeptidase N gene in pigs.
AB  - Intestinal infections with F4 enterotoxigenic Escherichia coli (ETEC) are
      worldwide an important cause of diarrhea in neonatal and recently weaned pigs.
      Adherence of F4 ETEC to the small intestine by binding to specific receptors is
      mediated by F4 fimbriae. Porcine aminopeptidase N (ANPEP) was recently identified
      as a new F4 receptor. In this study, 7 coding mutations and 1 mutation in the 3'
      untranslated region (3' UTR)were identified in ANPEP by reverse transcriptase (RT
      ) PCR and sequencing using 3 F4 receptor-positive (F4R+) and 2 F4 receptor
      negative (F4R-) pigs, which were F4 phenotyped based on the MUC4 TaqMan, oral
      immunization, and the in vitro villous adhesion assay. Three potential
      differential mutations (g.2615C > T, g.8214A > G, and g.16875C > G) identified by
      comparative analysis between the 3 F4R+ and 2 F4R- pigs were genotyped in 41
      additional F4 phenotyped pigs. However, none of these 3 mutations could be
      associated with F4 ETEC susceptibility. In addition, the RT-PCR experiments did
      not reveal any differential expression or alternative splicing in the small
      intestine of F4R+ and F4R- pigs. In conclusion, we hypothesize that the
      difference in F4 binding to ANPEP is due to modifications in its carbohydrate
      moieties. 

PMID- 24663208
TI  - Effects of a dietary sweetener on growth performance and health of stressed beef
      calves and on diet digestibility and plasma and urinary metabolite concentrations
      of healthy calves.
AB  - Two experiments were conducted to explore the effects of a sodium saccharin-based
      dietary sweetener (Sucram) on growth performance, health, and physiological
      responses of feedlot steers. In Exp. 1, 173 newly-received male calves purchased
      from auction barns were fed 0, 100, 200, or 300 g of Sucram/t of DM over 56 d.
      Overall, ADG and G:F (P > 0.10) were not different among treatments, but steers
      receiving 200 g Sucram/t displayed numerically greater ADG (23%). In addition,
      DMI was 17% greater for steers receiving 200 g of Sucram/t compared to steers fed
      the control diet (cubic effect, P = 0.09). The morbidity rate for respiratory
      disease did not differ (P > 0.50) among treatments. In Exp. 2, 15 steers (initial
      BW = 261 +/- 28 kg) were used to evaluate the effects of Sucram on apparent total
      tract digestibility, plasma metabolite concentrations, and urine monoamine
      metabolite concentrations. Treatments consisted of ad libitum access to a 60%
      concentrate diet (Control), ad libitum access to Control + 200 g of Sucram/t of
      DM (Adlib), and Control + 200 g of Sucram/t of DM with feed intake paired to the
      Control (Paired). By design, steer DMI during the metabolism period did not
      differ (P = 0.34) between Paired and Control, but DMI tended (P = 0.14) to be
      8.2% greater for Adlib than for Control. Treatments did not alter (P > 0.17)
      apparent total tract nutrient digestibility. Postprandial plasma citrulline
      concentration was lower (P = 0.03) for Adlib than for Control and tended to be
      lower (P = 0.13) for Paired than for Control. Plasma homocysteine concentration
      was reduced (P < 0.03) by feeding Sucram. Urinary concentrations of ethylmalonic
      acid, vanillymandelic acid, and 5-hydroxyindolacetic acid were greater (P < 0.06)
      for Adlib than for Control; Paired steers had a greater (P = 0.02) urine
      vanillymandelic acid concentration than Control steers and tended (P < 0.12) to
      have a greater urinary concentration of ethylmalonic and 5-hydroxyindolacetic
      acid than Control steers. Serum insulin was greater for Adlib than for Control
      steers (P = 0.04) and tended to be greater for Paired than for Control steers (P
      = 0.14), but serum prolactin area did not differ (P > 0.22) among treatments.
      Supplementation with Sucram may increase feed intake by newly-received, stressed
      feedlot calves. Saccharin supplementation reduced plasma homocysteine and
      increased urinary excretion of vanillymandelic acid, suggesting an improved
      activity of the dopamine reward system. 

PMID- 24663209
TI  - Comparison of organic and inorganic zinc sources to maximize growth and meet the
      zinc needs of the nursery pig.
AB  - Zinc is the trace element involved in more biological functions than any other
      micromineral in the nutrition of the newly weaned pig. Its role in growth via
      protein synthesis and antioxidant defense makes it a key nutrient in the diet of
      the newly weaned nursery pig for maximum lean tissue growth and health. In this
      study, 500 pigs (5 pigs/pen) were weaned at approximately 18 d of age and fed 0,
      25, 50, 75, or 100 mg/kg of Zn supplied as organic or inorganic Zn or 50 mg Zn/kg
      combination with 50% Zn from each source. Pigs were killed at 0, 10, and 35 d of
      the study to determine mineral tissue concentrations and antioxidant activity in
      the liver and the amount of metallothionein (MT) protein in the liver, duodenum,
      and jejunum. Growth performance did not differ for the pigs supplemented with Zn
      but were greater than those fed the basal diet with no added Zn (P <= 0.05).
      Hepatic Zn concentration was numerically maximized with 75 mg/kg of organic Zn,
      but 100 mg/kg of Zn of inorganic Zn was necessary to achieve a similar
      concentration. At d 10, Mn superoxide dismutase in pigs fed no supplemental Zn
      was lower than when pigs were fed organic Zn (P <= 0.05). Hepatic MT responded in
      a linear manner with organic Zn (P <= 0.01) and pigs fed the basal diet had less
      than those supplemented with Zn (P <= 0.01). Duodenal MT was greater at d 10 with
      organic Zn (P <= 0.01) than pigs fed the basal diet, and at d 35, there was a
      linear response to both organic and inorganic Zn (P <= 0.01). As expected,
      jejunal MT was reduced compared to this protein in the duodenum. The provision of
      Zn at 50 mg/kg from either source resulted in greater jejunal MT than when Zn was
      fed as a combination of both sources at the same concentration (P <= 0.05). Our
      data indicate that the needs of the nursery pig, that is, Zn requirements for
      health and well-being, have changed since the data used to establish the 2012
      Nutrient Requirements of Swine (NRC, 2012) was published. Organic minerals are
      shown in this study to be managed biologically in a different manner than
      inorganic Zn (sulfate) in the young pig. The newly weaned pig, while changing
      nutritional sources and physical environments, has extremely high biological
      demand for antioxidant defense. Our data show that to maximize growth, health,
      and well-being, 75 mg/kg of organic Zn in a complex nursery diet benefits today's
      fast growing pigs with a very high lean tissue composition. 

PMID- 24663210
TI  - Estimation of U.S. Yorkshire breed composition using genomic data.
AB  - The Yorkshire breed uses white coat color as a selection requirement to indicate
      breed purity. In this study, genomic information from chromosomal regions, as
      well as the whole genome, was applied to estimate breed composition of purebred
      Yorkshire animals. Genotypes for approximately 60,000 SNP from the Illumina
      PorcineSNP60 BeadChip (60K) were available for reference animals for which the
      genetic background was known, study animals that included Yorkshire sires
      (Tes_York, n = 889), and known crossbred animals that had Yorkshire heritage
      (Tes_U, n = 12). Haplotypes of SNP flanking the KIT (Dominant white locus) and
      MC1R (Melanocortin receptor 1) genes were developed for reference animals for the
      Duroc, Hampshire, Landrace, Yorkshire, and Pietrain breeds. For the KIT region,
      haplotypes observed in Yorkshire reference animals were also found in 84 and 7%
      of the haplotypes in Landrace and Pietrain reference animals, respectively. They
      were not found in Duroc or Hampshire reference animals. The sensitivity and
      specificity of haplotype analysis was 0.93 and 0.75, respectively. In addition,
      whole genome SNP information was used in regression analyses to further
      differentiate breed composition. Using 60K, 90% of regression coefficients for
      Yorkshire, indicating relative Yorkshire composition, ranged from 0.791 to 1.073
      and 0.524 to 1.06 in Tes_York and Tes_U, respectively. Regression coefficients
      for 90% of Hampshire ranged from -0.029 to 0.052 and -0.005 to 0.379 in Tes_York
      and Tes_U, respectively. Animals in Tes_U were likely of Yorkshire and Hampshire
      breed origin. The sensitivity and specificity of regression analysis was 0.96 and
      0.58, respectively. Combining haplotype and regression analyses, 810 Tes_York
      animals were accepted as purebred Yorkshire. Genomic information can be used as a
      tool to describe an animal's breed composition and reduce the need for progeny
      testing for white coat color verification. 

PMID- 24663211
TI  - A disintegrin and metalloprotease-12 is type I myofiber specific in Bos taurus
      and Bos indicus cattle.
AB  - A disintegrin and metalloproteinase-12 (ADAM12) is involved in the regulation of
      myogenesis and adipogenesis and is of interest as a potential target to
      manipulate skeletal muscle development and intramuscular fat (IMF) deposition in
      cattle to increase beef yield and improve meat quality. The longissimus thoracis
      muscle (LM) and semitendinosus muscle (STM) from 5 Bos taurus (Angus) and 5 Bos
      indicus (Brahman) cattle were collected for histological and ADAM12 gene and
      protein expression analysis. Myofiber typing was used to determine if ADAM12
      expression patterns related to differences in muscling and IMF deposition, which
      are influenced by proportions of the different myofiber types. The STM was found
      to contain a higher proportion of glycolytic myofibers than the LM, which
      contained a greater proportion of oxidative myofibers (myofiber ratio of
      glycolytic to more oxidative types in LM and STM of 1.1 and 3.5, respectively; P
      < 0.05). ADAM12 gene expression, fluorescent immunohistochemical staining for
      ADAM12, and image analysis found ADAM12 to be greater in the LM (P < 0.05).
      Regression analysis found a strong, positive relationship for the distribution of
      ADAM12 against the proportion of type I myofibers (P < 0.05, r(2) = 0.86). These
      findings suggest ADAM12 is upregulated in muscles with more slow-oxidative
      myofibres, such as the LM, and is linked to type I myofibers in cattle. ADAM12
      may be important in the regulation and maintenance slow myofibers in the LM
      muscle.

PMID- 24663212
TI  - Feeding behavior, ruminal fermentation, and performance of pregnant beef cows
      differing in phenotypic residual feed intake offered grass silage.
AB  - This study examined the relationship of residual feed intake (RFI) and
      performance with feeding behavior and ruminal fermentation variables in pregnant
      beef cows offered a grass silage diet. Individual grass silage DMI (dry matter
      digestibility = 666 g/kg) was recorded on 47 gestating (mean gestation d 166, SD
      = 26 d) Simmental and Simmental * Holstein-Friesian beef cows for a period of 80
      d. Cow BW, BCS, skeletal measurements, ultrasonically scanned muscle and fat
      depth, visual muscular score, ruminal fermentation, blood metabolites, and
      feeding behavior were measured. Phenotypic RFI was calculated as actual DMI minus
      expected DMI. Expected DMI was computed for each animal by regressing DMI on
      conceptus-adjusted mean BW(0.75) and ADG over an 80-d period. Within breed, cows
      were ranked by RFI into low (efficient), medium, or high groups. Overall mean
      (SD) values for DMI (kg/d), RFI, initial conceptus-adjusted BW, and conceptus
      adjusted ADG were 8.41 (1.09) kg/d, 0.01 (0.13) kg/d, 646 (70) kg, and -0.07
      (0.32) kg, respectively. High-RFI cows ate 25% and 8% more than low- and medium
      RFI cows, respectively. Live weight and ADG were not correlated (P > 0.05), and
      DMI was positively correlated (r = 0.80; P < 0.001) with RFI. The low- and high
      RFI groups had similar (P > 0.05) BW, ADG, BCS, visual muscular scores, skeletal
      measurements, blood metabolites, calf birth weight, and calving difficulty
      scores. All ultrasonic fat and muscle depth measurements were similar (P > 0.05)
      for low- and high-RFI cows except for back fat thickness change, where low-RFI
      cows gained less fat (P < 0.05) than high-RFI cows. Low-RFI cows had greater pH
      and lower ammonia concentrations in ruminal fluid compared to their high-RFI
      contemporaries. Low-RFI cows had fewer (P < 0.001) daily feeding events, but
      these were of longer (P < 0.001) duration (min.feed event(-1).d(-1)). Despite
      this, total daily duration of feeding was shorter (P < 0.001; min/d) for low-
      compared to high-RFI cows. High-RFI cows had more and a longer total duration of
      nonfeeding events (P < 0.001) than low-RFI cows. This study showed that compared
      to cows with high RFI, those with low RFI consumed less feed for similar levels
      of productivity, spent less time engaged in feeding-behavior-related activities,
      and differed in ruminal fermentation parameters. Feeding events are a significant
      (17%) contributory factor to variation in RFI in pregnant beef cows offered grass
      silage. 

PMID- 24663213
TI  - Obese and lean porcine difference of FoxO1 and its regulation through C/EBPbeta
      and PI3K/GSK3beta signaling pathway.
AB  - Forkhead box O 1 (FoxO1) is an important transcription factor implicated in
      adipogenesis. In this study, we detected the breed differences in FoxO1 between
      Bamei pigs (an obese breed) and Large White pigs (a lean breed). Compared with
      Large White pigs, the BW of Bamei pigs was lower (P < 0.01), but back fat
      thickness, fat percent, and intramuscular fat content were greater (P < 0.01).
      The levels of FoxO1 mRNA and protein were lower (P < 0.01) in subcutaneous
      adipose tissue (SAT) of Bamei pigs at 180 d, adipocytes and stromal-vascular
      fraction extracted from SAT of Bamei pigs at 1 d compared with Large White pigs.
      Knockdown of FoxO1 increased triglyceride content (P < 0.01) and upregulated the
      levels of adipocyte fatty-acid binding protein, PPARgamma, and CCAAT enhancer
      binding protein alpha (C/EBPalpha) at 6 d after porcine preadipocytes were
      induced. Furthermore, the transcriptional regulation of FoxO1 through C/EBPbeta
      during early porcine preadipocyte differentiation and the effect of insulin on
      phosphoinositide 3 kinase (PI3K)/glycogen synthase kinase 3beta (GSK3beta) signal
      pathway by FoxO1 were examined. The results indicated that FoxO1 inhibited
      transcription activity of C/EBPbeta, whereas C/EBPbeta did not affect
      transcription activity of FoxO1. At 6 and 12 h of early differentiation,
      knockdown of FoxO1 triggered the transcription activity of C/EBPbeta. In
      addition, FoxO1 protein interacted with C/EBPbeta protein in porcine adipocytes
      at 12 h after induction. Under treatment with 100 nM insulin, knockdown or
      overexpression of FoxO1 mediated PI3K/GSK3beta signaling via upregulating or
      downregulating the levels of GSK3beta and its phosphorylation in adipocytes.
      Taken together, there is low, but detectable, expression of FoxO1 in SAT of obese
      pigs and FoxO1 inhibited adipogenesis through C/EBPbeta and PI3K/GSK3beta
      signaling pathway. These findings provide useful information to further the
      understanding of the function of FoxO1 in porcine adipogenesis. 

PMID- 24663214
TI  - RNA editing in RHOQ promotes invasion potential in colorectal cancer.
AB  - RNA editing can increase RNA sequence variation without altering the DNA
      sequence. By comparing whole-genome and transcriptome sequence data of a rectal
      cancer, we found novel tumor-associated increase of RNA editing in ras homologue
      family member Q (RHOQ) transcripts. The adenosine-to-inosine (A-to-I) editing
      results in substitution of asparagine with serine at residue 136. We observed a
      higher level of the RHOQ RNA editing in tumor compared with normal tissue in
      colorectal cancer (CRC). The degree of RNA editing was associated with RhoQ
      protein activity in CRC cancer cell lines. RhoQ N136S amino acid substitution
      increased RhoQ activity, actin cytoskeletal reorganization, and invasion
      potential. KRAS mutation further increased the invasion potential of RhoQ N136S
      in vitro. Among CRC patients, recurrence was more frequently observed in patients
      with tumors having edited RHOQ transcripts and mutations in the KRAS gene. In
      summary, we show that RNA editing is another mechanism of sequence alteration
      that contributes to CRC progression. 

PMID- 24663215
TI  - IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in
      the absence of differentiated FDCs.
AB  - Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in
      the lung, develops spontaneously at sites of chronic inflammation or during
      infection. The molecular mechanisms underlying the neogenesis of such tertiary
      lymphoid tissue are still poorly understood. We show that the type of
      inflammation-inducing pathogen determines which key factors are required for the
      formation and maturation of BALT. Thus, a single intranasal administration of the
      poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly
      organized BALT with densely packed B cell follicles containing a network of
      CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular
      stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT
      but B cell follicles lack FDCs while still harboring CXCL12-positive follicular
      stromal cells. Furthermore, in IL-17-deficient mice, P.a.-induced BALT largely
      lacks B cells as well as CXCL12-expressing stromal cells, and only loose
      infiltrates of T cells are present. We show that Toll-like receptor pathways are
      required for BALT induction by P.a., but not MVA, and provide evidence that IL-17
      drives the differentiation of lung stroma toward podoplanin-positive CXCL12
      expressing cells that allow follicle formation even in the absence of FDCs. Taken
      together, our results identify distinct pathogen-dependent induction and
      maturation pathways for BALT formation. 

PMID- 24663216
TI  - The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and
      directly regulates Eomes and Id2 expression.
AB  - The transcription factor E4bp4 (Nfil3) is essential for natural killer (NK) cell
      production. Here, we show that E4bp4 is required at the NK lineage commitment
      point when NK progenitors develop from common lymphoid progenitors (CLPs) and
      that E4bp4 must be expressed at the CLP stage for differentiation toward the NK
      lineage to occur. To elucidate the mechanism by which E4bp4 promotes NK
      development, we identified a central core of transcription factors that can
      rescue NK production from E4bp4(-/-) progenitors, suggesting that they act
      downstream of E4bp4. Among these were Eomes and Id2, which are expressed later in
      development than E4bp4. E4bp4 binds directly to the regulatory regions of both
      Eomes and Id2, promoting their transcription. We propose that E4bp4 is required
      for commitment to the NK lineage and promotes NK development by directly
      regulating the expression of the downstream transcription factors Eomes and Id2. 

PMID- 24663217
TI  - Protective effects of combined intervention with adenovirus vector mediated IL-10
      and IGF-1 genes on endogenous islet beta cells in nonobese diabetes mice with
      onset of type 1 diabetes mellitus.
AB  - OBJECTIVE: To investigate the protective effects of combined intervention with
      adenovirus vector mediated interleukin 10 (IL-10) and insulin-like growth factor
      1 (IGF-1) genes on islet beta cells in nonobese diabetes (NOD) mice with type 1
      diabetes mellitus (T1D) at early stage. METHODS: Twenty-four female NOD mice at
      onset of diabetes and aged 17-20 weeks old were randomly divided into four
      groups. Mouse 1, 2 and 3 groups were intraperitoneally injected 0.1 ml of Ad-mIGF
      1, Ad-mIL-10, and combined Ad-mIGF-1 and Ad-mIL-10, respectively. Mouse 4 group
      were used as diabetes control. In addition, six age- and sex-matched non-diabetic
      NOD mice were intraperitoneally injected 0.1 ml of PBS and assigned 5 group as
      normal controls. All mice were weekly monitored for body weight, urine glucose
      and blood glycose, and sacrificed 3 weeks after injection. Their serum levels of
      IL-10, IGF-1, IFN-gamma, IL-4 and C-peptide were measured and the degree of
      insulitis and the local expression of IGF-1 and IL-10 gene were observed.
      RESULTS: 1) IL-10 and IGF-1 levels in serum and pancreas were enhanced in 1, 2,
      and 3 groups; 2) serum INF-gamma level was decreased while serum IL-10 and IL-4
      levels were increased in 1, 2 and 3 groups, and these alterations were more
      significant in 3 group than 1 and 2 groups (P<0.01); 3) C-peptide level was not
      enhanced in 1 group, but significantly increased in 2 and 3 groups, and these
      increases were more significant in the latter (P<0.01); 4) Three weeks later, the
      body mass of mice in 2 and 3 groups decreased significantly (P<0.05). CONCLUSION:
      The administration of adenovirus vector mediated IL-10 and/or IGF-1 gene showed
      limited immune regulatory and protective effects on islet beta-cells in NOD mice
      with T1D at early stage, and no significant reduction in insulitis, blood glucose
      and body weight.

PMID- 24663219
TI  - Thyroid function. Pathogenesis of Graves ophthalmopathy--a role for TSH-R?
AB  - A new study highlights the complexities of anti-TSH-receptor antibody function
      and the differences between adult and paediatric patients with Graves disease,
      adding to the controversy regarding the possible role of these antibodies in the
      development of ophthalmopathy.

PMID- 24663218
TI  - Catalase (KatA) plays a role in protection against anaerobic nitric oxide in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa (PA) is a common bacterial pathogen, responsible for a
      high incidence of nosocomial and respiratory infections. KatA is the major
      catalase of PA that detoxifies hydrogen peroxide (H2O2), a reactive oxygen
      intermediate generated during aerobic respiration. Paradoxically, PA displays
      elevated KatA activity under anaerobic growth conditions where the substrate of
      KatA, H2O2, is not produced. The aim of the present study is to elucidate the
      mechanism underlying this phenomenon and define the role of KatA in PA during
      anaerobiosis using genetic, biochemical and biophysical approaches. We
      demonstrated that anaerobic wild-type PAO1 cells yielded higher levels of katA
      transcription and expression than aerobic cells, whereas a nitrite reductase
      mutant DeltanirS produced ~50% the KatA activity of PAO1, suggesting that a basal
      NO level was required for the increased KatA activity. We also found that
      transcription of the katA gene was controlled, in part, by the master anaerobic
      regulator, ANR. A DeltakatA mutant and a mucoid mucA22 DeltakatA bacteria
      demonstrated increased sensitivity to acidified nitrite (an NO generator) in
      anaerobic planktonic and biofilm cultures. EPR spectra of anaerobic bacteria
      showed that levels of dinitrosyl iron complexes (DNIC), indicators of NO stress,
      were increased significantly in the DeltakatA mutant, and dramatically in a
      DeltanorCB mutant compared to basal levels of DNIC in PAO1 and DeltanirS mutant.
      Expression of KatA dramatically reduced the DNIC levels in DeltanorCB mutant. We
      further revealed direct NO-KatA interactions in vitro using EPR, optical
      spectroscopy and X-ray crystallography. KatA has a 5-coordinate high spin ferric
      heme that binds NO without prior reduction of the heme iron (Kd ~6 MUM).
      Collectively, we conclude that KatA is expressed to protect PA against NO
      generated during anaerobic respiration. We proposed that such protective effects
      of KatA may involve buffering of free NO when potentially toxic concentrations of
      NO are approached. 

PMID- 24663221
TI  - Obesity. BMI-associated genetic variants in FTO mastermind IRX3 expression.

PMID- 24663220
TI  - Autophagy--a key player in cellular and body metabolism.
AB  - Knowledge gained over the past 10 years about the mechanisms that underpin
      autophagy has provided a universal framework for studies of diverse physiological
      and pathological processes. Of particular interest is the emerging role of
      autophagy in the maintenance of energy homeostasis, both at the cellular level
      and within the organism as a whole. Dysregulation of autophagy might contribute
      to the development of metabolic disorders, including insulin resistance, diabetes
      mellitus, obesity, atherosclerosis and osteoporosis. The authors of this Review
      highlight research findings on the regulation of cellular autophagy by nutrients.
      They also describe the role of autophagy in various tissues in the regulation of
      energy metabolism and the development of diseases related to altered metabolism.
      Finally, the potential of pharmacological modulation of autophagy as a treatment
      for human metabolic disorders is discussed. 

PMID- 24663224
TI  - Effective utilization of waste water through recycling, reuse, and remediation
      for sustainable agriculture.
AB  - Water is vital for human, animal, and plant life. Water is one of the most
      essential inputs for the production of crops. Plants need it in enormous
      quantities continuously during their life. The role of water is felt everywhere;
      its scarcity causes droughts and famines, its excess causes floods and deluge.
      During the next two decades, water will increasingly be considered a critical
      resource for the future survival of the arid and semiarid countries. The
      requirement of water is increasing day by day due to intensive agriculture
      practices, urbanization, population growth, industrialization, domestic use, and
      other uses. On the other hand, the availability of water resources is declining
      and the existing water is not enough to meet the needs. To overcome this problem,
      one available solution is utilization of waste water by using recycling, reuse,
      and remediation process.

PMID- 24663222
TI  - Insulin resistance and hyperglycaemia in cardiovascular disease development.
AB  - The prevalence of diabetes mellitus will likely increase globally from 371
      million individuals in 2013 to 552 million individuals in 2030. This epidemic is
      mainly attributable to type 2 diabetes mellitus (T2DM), which represents about 90
      95% of all cases. Cardiovascular disease is the leading cause of mortality among
      individuals with diabetes mellitus, and >50% of patients will die from a
      cardiovascular event-especially coronary artery disease, but also stroke and
      peripheral vascular disease. Classic risk factors such as elevated levels of LDL
      cholesterol and blood pressure, as well as smoking, are risk factors for adverse
      cardiovascular events in patients with type 1 diabetes mellitus (T1DM) and T2DM
      to a similar degree as they are in healthy individuals. Patients with T1DM
      develop insulin resistance in the months after diabetes mellitus diagnosis, and
      patients with T2DM typically develop insulin resistance before hyperglycaemia
      occurs. Insulin resistance and hyperglycaemia, in turn, further increase the risk
      of adverse cardiovascular events. This Review discusses the mechanisms by which
      T1DM and T2DM can lead to cardiovascular disease and how these relate to the risk
      factors for coronary artery disease. 

PMID- 24663225
TI  - First-trimester fetal growth discordance and development of preeclampsia in
      dichorionic twin pregnancies.
AB  - OBJECTIVE: To investigate the relation between first-trimester fetal growth
      discrepancy, as assessed by crown-rump length (CRL) at 11+0 to 13+6 weeks of
      gestation, and subsequent development of preeclampsia (PE) in dichorionic
      diamniotic (DCDA) twin pregnancies. The association between inter-twin CRL and
      birth weight (BW) discrepancy was also investigated. METHODS: This was a
      retrospective, case-control study of DCDA twin pregnancies. Inter-twin CRL
      discrepancy was calculated as 100*(larger CRL-smaller CRL)/larger CRL. BW
      discordance was calculated as 100*(larger BW-smaller BW)/larger BW. RESULTS: The
      study included 299 DCDA pregnancies that remained normotensive and 35 that
      subsequently developed PE. There was no significant difference in the inter-twin
      CRL discrepancy between pregnancies complicated by PE and those that were not
      [3.2%, interquartile range (IQR): 0.5-4.5% vs. 3.3%, IQR: 1.4-5.5%; P=0.17].
      There was a positive correlation between inter-twin CRL and BW discrepancy but
      only in pregnancies that remained normotensive (P<0.001). In women that
      subsequently developed PE, there was no association between inter-twin CRL and BW
      discordance (P=0.54). CONCLUSIONS: In unselected DCDA twins, first-trimester CRL
      discrepancy is not different between pregnancies that subsequently develop PE and
      those that remain normotensive. Furthermore, in pregnancies that are complicated
      by PE, the association between inter-twin CRL and BW discrepancy appears to be
      lost.

PMID- 24663223
TI  - Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids.
AB  - The link between chronic psychosocial and metabolic stress and the pathogenesis
      of disease has been extensively documented. Nevertheless, the cellular mechanisms
      by which stressful life experiences and their associated primary neuroendocrine
      mediators cause biological damage and increase disease risk remain poorly
      understood. The allostatic load model of chronic stress focuses on glucocorticoid
      dysregulation. In this Perspectives, we expand upon the metabolic aspects of this
      model-particularly glucose imbalance-and propose that mitochondrial dysfunction
      constitutes an early, modifiable target of chronic stress and stress-related
      health behaviours. Central to this process is mitochondrial regulation of energy
      metabolism and cellular signalling. Chronically elevated glucose levels damage
      both mitochondria and mitochondrial DNA, generating toxic products that can
      promote systemic inflammation, alter gene expression and hasten cell ageing.
      Consequently, the concept of 'mitochondrial allostatic load' defines the
      deleterious structural and functional changes that mitochondria undergo in
      response to elevated glucose levels and stress-related pathophysiology. 

PMID- 24663226
TI  - The IgG avidity value for the prediction of congenital cytomegalovirus infection
      in a prospective cohort study.
AB  - BACKGROUND: Cytomegalovirus (CMV) causes congenital infection with high mortality
      and morbidity rates in affected neonates. OBJECTIVES: To evaluate the maternal
      IgG avidity value for the prediction of congenital CMV infection. STUDY DESIGN:
      The serum IgG avidity in all mothers was measured, and the urine of their
      neonates was assessed for CMV DNA in a prospective cohort study. RESULTS: Of 759
      women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG
      avidity indices in the congenital infection group (median 35.1%) were
      significantly lower than those in the non-congenital infection group (70.4%). A
      cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3%
      sensitivity for congenital infection was determined by receiver operating
      characteristic curve analyses. The highest sensitivity (88.9%), 96.2%
      specificity, 27.6% positive predictive value, 99.8% negative predictive value,
      and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of
      gestation. CONCLUSION: The IgG avidity measurement with a cutoff value of <40%
      IgG avidity index might be helpful in predicting congenital CMV infection,
      especially in <28 weeks of gestation.

PMID- 24663227
TI  - Balloon tamponade for the management of postpartum uterine hemorrhage.
AB  - OBJECTIVE: To evaluate the use of the Bakri balloon in postpartum hemorrhage
      (PPH) resistant to medical treatment. METHODS: The Bakri balloon was applied to
      45 women with PPH after failure of initial management. Bilateral internal iliac
      artery ligation (BIIAL) and hysterectomy were performed if necessary. RESULTS:
      The Bakri balloon was applied in 45 women; an additional BIIAL was required in
      nine women. The mean inflation volume of the Bakri balloon was 571+/-264 mL
      (range: 240-1300 mL). Hemostasis was achieved in 34 (75.5%) women with the Bakri
      balloon alone, and in six women with an additional BIIAL. The Bakri balloon was
      effective with additional procedures overall in 40 of 45 (88.8%) women. In 34
      women with uterine atony, the Bakri balloon was successful alone in 27 (79.4%)
      and with an additional BIIAL in 30 (88.2%) women. An inflation volume of >500 mL
      was necessary in 18 women with uterine atony. CONCLUSION: The Bakri balloon may
      be performed as a first line of treatment for PPH resistant to uterotonic agents,
      and can be used not only in tertiary centers but also in limited-resource
      centers. The inflation volume of the Bakri balloon should be adjusted according
      to the type of PPH; a volume exceeding 500 mL may be necessary in uterine atony.

PMID- 24663228
TI  - Novel insights into the potential involvement of 5-HT7 receptors in endocrine
      dysregulation in stress-related disorders.
AB  - A hyperactive hypothalamic-pituitary-adrenal (HPA) axis is a common feature of
      stress-related disorders, and the brain serotonin (5-HT) system plays a major
      role in HPA axis modulation. Glucocorticoids and stress profoundly affect the 5
      HT system so it is possible that alterations of endocrine 5-HT mechanisms may
      underlie HPA axis overdrive in stress-related diseases. Available evidence
      suggests a role of 5-HT1A, 5-HT2A/2C and 5-HT7 receptors in HPA system
      activation, and pharmacological blockade of 5-HT7 receptors produces a fast
      acting antidepressant-like action and shortens the onset of antidepressant-like
      effects of various classes of antidepressants. The mechanisms involved in this
      effect have not been elucidated, but recent findings suggest a role of 5-HT7
      receptors in the development of HPA axis overdrive as a result of chronic stress.
      Remarkably, clinical findings have shown an association between corticosteroid
      producing adenomas and expression of ectopic 5-HT7 receptors in corticosteroid
      producing adrenocortical cells. These observations might therefore reveal an
      endocrine mechanism for the antidepressant-like action of 5-HT7 receptor
      blockers, possibly through normalization of HPA axis function. If such a
      preliminary hypothesis is confirmed, the potential therapeutic usefulness of 5
      HT7 receptor antagonists could extend beyond depression to include other
      diseases, the pathophysiology of which has been associated with chronic stress
      and HPA axis dysregulation.

PMID- 24663229
TI  - A decade of racial and ethnic stroke disparities in the United States.
AB  - Stroke is the fourth leading cause of death and the leading cause of long-term
      disability in the United States. Stroke incidence and prevalence is not uniform.
      It occurs more frequently in some geographical areas of the United States and the
      rates are higher in minority groups.(1,2) Some proposed causes for these
      disparities include increased rate of vascular risk factors that
      disproportionally affect some minority groups, differential effect of
      hypertension on stroke risk across racial groups, lack of access to health care
      and other social determinants of health, suboptimal control of risk factors, and
      although lacking substantive data to date, an inherited predisposition to stroke
      associated with genetic differences. The Reasons for Geographic and Racial
      Differences in Stroke (REGARDS) investigators found that the rate of suboptimal
      control of vascular risk factors and unhealthy lifestyles were significantly
      greater in African Americans compared to non-Hispanic whites (NHW).(2) Moreover,
      regarding high blood pressure (BP), a triple threat has been described: blacks
      are not only more likely to have high BP, they are less likely, once diagnosed,
      to have their high BP controlled, and this suboptimal control has been shown to
      confer a stroke risk that is 3 times higher among blacks compared to whites for
      every 10-mm Hg increase in systolic BP (SBP).(3.) 

PMID- 24663230
TI  - Summary of evidence-based guideline: complementary and alternative medicine in
      multiple sclerosis: report of the guideline development subcommittee of the
      American Academy of Neurology.
AB  - OBJECTIVE: To develop evidence-based recommendations for complementary and
      alternative medicine (CAM) in multiple sclerosis (MS). METHODS: We searched the
      literature (1970-March 2011; March 2011-September 2013 MEDLINE search),
      classified articles, and linked recommendations to evidence. RESULTS AND
      RECOMMENDATIONS: Clinicians might offer oral cannabis extract for spasticity
      symptoms and pain (excluding central neuropathic pain) (Level A). Clinicians
      might offer tetrahydrocannabinol for spasticity symptoms and pain (excluding
      central neuropathic pain) (Level B). Clinicians should counsel patients that
      these agents are probably ineffective for objective spasticity (short
      term)/tremor (Level B) and possibly effective for spasticity and pain (long-term)
      (Level C). Clinicians might offer Sativex oromucosal cannabinoid spray
      (nabiximols) for spasticity symptoms, pain, and urinary frequency (Level B).
      Clinicians should counsel patients that these agents are probably ineffective for
      objective spasticity/urinary incontinence (Level B). Clinicians might choose not
      to offer these agents for tremor (Level C). Clinicians might counsel patients
      that magnetic therapy is probably effective for fatigue and probably ineffective
      for depression (Level B); fish oil is probably ineffective for relapses,
      disability, fatigue, MRI lesions, and quality of life (QOL) (Level B); ginkgo
      biloba is ineffective for cognition (Level A) and possibly effective for fatigue
      (Level C); reflexology is possibly effective for paresthesia (Level C); Cari
      Loder regimen is possibly ineffective for disability, symptoms, depression, and
      fatigue (Level C); and bee sting therapy is possibly ineffective for relapses,
      disability, fatigue, lesion burden/volume, and health-related QOL (Level C).
      Cannabinoids may cause adverse effects. Clinicians should exercise caution
      regarding standardized vs nonstandardized cannabis extracts and overall CAM
      quality control/nonregulation. Safety/efficacy of other CAM/CAM interaction with
      MS disease-modifying therapies is unknown.

PMID- 24663231
TI  - Redundant dopaminergic activity may enable compensatory axonal sprouting in
      Parkinson disease.
AB  - Neurodegenerative diseases become clinically apparent only after a substantial
      population of neurons is lost. This raises the possibility of compensatory
      mechanisms in the early phase of these diseases. The importance of understanding
      these mechanisms cannot be underestimated because it may guide future disease
      modifying strategies. Because the anatomy and physiology of the nigrostriatal
      dopaminergic pathways have been well described, the study of Parkinson disease
      can offer insight into these early compensatory mechanisms. Collateral axonal
      sprouting of dopaminergic terminals into the denervated striatum is the most
      studied compensatory mechanism in animal (almost exclusively rodent) models of
      Parkinson disease and is correlated with behavioral recovery after partial
      lesions. This sprouting, however, does not respect the normal anatomy of the
      original nigrostriatal pathways and leads to aberrant neuronal networks. We
      suggest here that the unique physiologic property of the dopaminergic innervation
      of the striatum, namely redundancy of information encoding, is crucial to the
      efficacy of compensatory axonal sprouting in the presence of aberrant anatomical
      connections. Redundant information encoding results from the similarity of
      representation of salient and rewarding events by many dopaminergic neurons, from
      the wide axonal field of a single dopaminergic neuron in the striatum, and from
      the nonspecific spatial effect of dopamine on striatal neurons (volume
      conductance). Finally, we discuss the relevance of these findings in animal
      models to human patients with Parkinson disease. 

PMID- 24663232
TI  - A case of rabies encephalitis: new dog, old tricks.

PMID- 24663233
TI  - Acute late-onset encephalopathy after radiotherapy: an unusual life-threatening
      complication.

PMID- 24663234
TI  - White matter hyperintensities on MRI in high-altitude U-2 pilots.

PMID- 24663235
TI  - Teaching neuroimages: snowball-like lesions with sudden hearing loss.

PMID- 24663236
TI  - Teaching neuroimages: MRI in advanced neuromyelitis optica.

PMID- 24663237
TI  - Complementary and alternative medicine in multiple sclerosis.

PMID- 24663238
TI  - Mystery case: catathrenia: a rare but treatable parasomnia.

PMID- 24663239
TI  - Structural model for estimating the influence of cognitive reserve on cognitive
      performance in adults with subjective memory complaints.
AB  - Cognitive reserve (CR) is often operationally defined as a complex structure of
      latent variables. Here, we present a structural model that analyzes the effect of
      CR on three cognitive domains: episodic memory, working memory, and general
      cognitive performance. We developed and analyzed a structural equation model
      (SEM) to study CR and cognitive performance in 326 participants over 50 years old
      with subjective memory complaints. The CR construct was found to consist of two
      factors: (a) educational level and (b) lifestyle. The model revealed that CR had
      significant direct effects on episodic memory, working memory, and general
      cognitive performance, and indirect effects on episodic memory via working
      memory. As a latent construct, CR is related to cognitive performance in
      participants over 50 years with subjective memory complaints, and it should
      therefore be considered in the evaluation and diagnosis of such people. 

PMID- 24663240
TI  - Insights into ligand binding to PreQ1 Riboswitch Aptamer from molecular dynamics
      simulations.
AB  - Riboswitches play roles in transcriptional or translational regulation through
      specific ligand binding of their aptamer domains. Although a number of ligand
      bound aptamer complex structures have been solved, it is important to know ligand
      free conformations of the aptamers in order to understand the mechanism of
      specific binding by ligands. In this paper, preQ1 riboswitch aptamer domain from
      Bacillus subtilis is studied by overall 1.5 MUs all-atom molecular dynamics
      simulations We found that the ligand-free aptamer has a stable state with a
      folded P1-L3 and open binding pocket. The latter forms a cytosine-rich pool in
      which the nucleotide C19 oscillates between close and open positions, making it a
      potential conformation for preQ1 entrance. The dynamic picture further suggests
      that the specific recognition of preQ1 by the aptamer domain is not only
      facilitated by the key nucleotide C19 but also aided and enhanced by other
      cytosines around the binding pocket. These results should help to understand the
      details of preQ1 binding. 

PMID- 24663241
TI  - Identifying mRNA sequence elements for target recognition by human Argonaute
      proteins.
AB  - It is commonly known that mammalian microRNAs (miRNAs) guide the RNA-induced
      silencing complex (RISC) to target mRNAs through the seed-pairing rule. However,
      recent experiments that coimmunoprecipitate the Argonaute proteins (AGOs), the
      central catalytic component of RISC, have consistently revealed extensive AGO
      associated mRNAs that lack seed complementarity with miRNAs. We herein test the
      hypothesis that AGO has its own binding preference within target mRNAs,
      independent of guide miRNAs. By systematically analyzing the data from in vivo
      cross-linking experiments with human AGOs, we have identified a structurally
      accessible and evolutionarily conserved region (~10 nucleotides in length) that
      alone can accurately predict AGO-mRNA associations, independent of the presence
      of miRNA binding sites. Within this region, we further identified an enriched
      motif that was replicable on independent AGO-immunoprecipitation data sets. We
      used RNAcompete to enumerate the RNA-binding preference of human AGO2 to all
      possible 7-mer RNA sequences and validated the AGO motif in vitro. These findings
      reveal a novel function of AGOs as sequence-specific RNA-binding proteins, which
      may aid miRNAs in recognizing their targets with high specificity. 

PMID- 24663243
TI  - Granular cell tumor of the breast eliciting exuberant pseudoepitheliomatous
      hyperplasia.

PMID- 24663242
TI  - Hydrous ruthenium oxide nanoparticles anchored to graphene and carbon nanotube
      hybrid foam for supercapacitors.
AB  - In real life applications, supercapacitors (SCs) often can only be used as part
      of a hybrid system together with other high energy storage devices due to their
      relatively lower energy density in comparison to other types of energy storage
      devices such as batteries and fuel cells. Increasing the energy density of SCs
      will have a huge impact on the development of future energy storage devices by
      broadening the area of application for SCs. Here, we report a simple and scalable
      way of preparing a three-dimensional (3D) sub-5 nm hydrous ruthenium oxide (RuO2)
      anchored graphene and CNT hybrid foam (RGM) architecture for high-performance
      supercapacitor electrodes. This RGM architecture demonstrates a novel graphene
      foam conformally covered with hybrid networks of RuO2 nanoparticles and anchored
      CNTs. SCs based on RGM show superior gravimetric and per-area capacitive
      performance (specific capacitance: 502.78 F g(-1), areal capacitance: 1.11 F cm(
      2)) which leads to an exceptionally high energy density of 39.28 Wh kg(-1) and
      power density of 128.01 kW kg(-1). The electrochemical stability, excellent
      capacitive performance, and the ease of preparation suggest this RGM system is
      promising for future energy storage applications.

PMID- 24663244
TI  - Serum BDNF levels in relation to illness severity, suicide attempts, and central
      serotonin activity in patients with major depressive disorder: a pilot study.
AB  - The aim of this study was to test the hypothesis that serum levels of brain
      derived neurotrophic factor (BDNF) are correlated with the loudness dependence of
      auditory evoked potentials (LDAEP). The question of whether there is a difference
      in BDNF levels between depressive patients according to their illness severity,
      history of suicide attempts, and central serotonin activity was also addressed. A
      sample of 51 patients who met the criteria for major depressive disorder
      following diagnosis using axis I of the fourth edition of the Diagnostic and
      Statistical Manual of Mental Disorders - text revision comprised the study
      subjects. The patients were stratified into two subgroups based on their illness
      severity, history of suicide attempts, and their LDAEP values. The LDAEP was
      evaluated by measuring the auditory event-related potentials, and serum BDNF was
      measured using blood sampling before beginning medication with serotonergic
      agents. There was no difference in serum BDNF levels between the two patient
      subgroups. The subgroup with moderate-to-severe depression (n = 16) was
      reanalyzed after stratifying it into two subgroups according to LDAEP and BDNF
      values (dichotomized at the medians into low and high). The high-LDAEP subgroup
      had higher serum BDNF levels and total Barratt Impulsiveness Scale score than the
      low-LDAEP subgroup (p = 0.03 and 0.036, respectively). Serum BDNF levels were
      positively correlated with LDAEP and total Beck Hopelessness Scale (BHS) score (r
      = 0.56, p = 0.025, and r = 0.59, p = 0.016, respectively). The high-BDNF subgroup
      had a higher LDAEP and total BHS score than the low-BDNF subgroup (p = 0.046 and
      p = 0.011, respectively). This is the first study to demonstrate a relationship
      between the BDNF level and LDAEP in Asian depressive patients. Intriguingly, the
      high-BDNF subgroup (divided according to illness severity) exhibited a more
      severe psychopathology on some psychometric rating scales, a finding that
      conflicts with previous results. 

PMID- 24663245
TI  - Multiple white matter volume reductions in patients with panic disorder:
      relationships between orbitofrontal Gyrus volume and symptom severity and social
      dysfunction.
AB  - Numerous brain regions are believed to be involved in the neuropathology of panic
      disorder (PD) including fronto-limbic regions, thalamus, brain stem, and
      cerebellum. However, while several previous studies have demonstrated volumetric
      gray matter reductions in these brain regions, there have been no studies
      evaluating volumetric white matter changes in the fiber bundles connecting these
      regions. In addition, although patients with PD typically exhibit social,
      interpersonal and occupational dysfunction, the neuropathologies underlying these
      dysfunctions remain unclear. A voxel-based morphometry study was conducted to
      evaluate differences in regional white matter volume between 40 patients with PD
      and 40 healthy control subjects (HC). Correlation analyses were performed between
      the regional white matter volumes and patients' scores on the Panic Disorder
      Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients
      with PD demonstrated significant volumetric reductions in widespread white matter
      regions including fronto-limbic, thalamo-cortical and cerebellar pathways
      (p<0.05, FDR corrected). Furthermore, there was a significant negative
      relationship between right orbitofrontal gyrus (OFG) white matter volume and the
      severity of patients' clinical symptoms, as assessed with the PDSS. A significant
      positive relationship was also observed between patients' right OFG volumes and
      their scores on the GAF. Our results suggest that volumetric reductions in
      widespread white matter regions may play an important role in the pathology of
      PD. In particular, our results suggest that structural white matter abnormalities
      in the right OFG may contribute to the social, personal and occupational
      dysfunction typically experienced by patients with PD. 

PMID- 24663246
TI  - Shallow-water northern hemisphere Jaera (Crustacea, Isopoda, Janiridae) found on
      whale bones in the southern ocean deep sea: ecology and description of Jaera
      tyleri sp. nov.
AB  - The skeleton of a natural whale fall discovered in the Southern Ocean at 1,445 m
      was densely covered by one small, janirid isopod. Jaera tyleri sp. nov. is the
      first of its genus found in the southern hemisphere and in the deep sea and is
      described herein. Morphological and molecular investigations revealed the
      systematic position of this species new to science. Phylogenetic analysis of the
      18S locus confirms that this species falls in a strongly supported monophyletic
      clade of Jaera species. The whale bone habitat of J. tyleri sp. nov. is quite
      different from those of other species of the genus Jaera. The analysis of
      bathymetric and distribution patterns of the Janiridae in general and Jaera
      specifically confirm the unusualness of the habitat for this isopod species. The
      abundance of J. tyleri sp. nov. on the whale bones and its absence from other
      nearby habitats suggests it to be a whale-fall specialist. The analysis of the
      size-frequency distributions of J. tyleri sp. nov. suggests multimodal population
      structure with continuous breeding activity throughout the year. The fecundity of
      the species is low but in line with reduced fecundity observed in polar and small
      sized isopods. 

PMID- 24663247
TI  - Bilateral vocal cord palsy post thyroidectomy: lessons learnt.
AB  - Bilateral vocal cord paralysis is a known possible complication following thyroid
      surgery. It owes to the close relationship between the recurrent laryngeal nerve
      and the thyroid gland. The most feared complication of bilateral vocal cord
      paralysis is airway compromise. We report the case of a 39-year-old woman who
      underwent total thyroidectomy for multinodular goitre. The surgery was
      uneventful. However she developed stridor in the recovery bay needing intubation.
      We postulate that the cause was attributed to bilateral vocal cord paresis due to
      the use of the intraoperative nerve monitoring (IONM) whose high setting
      throughout the surgery was overlooked. She made a complete recovery without the
      need of a tracheostomy. We share our lessons learnt from this case. 

PMID- 24663248
TI  - Gastric variceal bleeding due to pancreatitis-induced splenic vein thrombosis.
AB  - Obscure gastrointestinal bleeding is a common clinical scenario. In the upper
      gastrointestinal tract, gastric varices can be frequently overlooked on
      endoscopy, particularly if not suspected or volume depleted. We report a case of
      suspected gastrointestinal bleeding in a patient with a childhood history of
      pancreatitis, who also experienced severe epigastric pain while in hospital.
      After transfer to an academic medical centre, the presence of gastric varices was
      identified and presumed to be due to splenic vein thrombosis. Pancreatitis is the
      most common cause of splenic vein thrombosis and accords with the patient's
      history, even though it occurred many years previously. This case highlights the
      importance of recognising pancreatitis-induced splenic vein thrombosis as a
      possible aetiology for upper gastrointestinal bleeding. 

PMID- 24663249
TI  - Boston type 1 based keratoprosthesis (Auro Kpro) and its modification (LVP Kpro)
      in chronic Stevens Johnson syndrome.
AB  - Two young women with completely dry and keratinised eyes post-Stevens Johnson
      Syndrome (SJS) underwent unilateral oral mucous membrane grafts (MMGs) in
      preparation for modified osteo-odonto keratoprosthesis (MOOKP) implantation. In
      both cases, the mucosal graft was deemed to be too tight to accommodate the MOOKP
      implant. Instead of proceeding with MOOKP, the first patient underwent Auro Kpro
      (Boston type 1-based keratoprosthesis) implantation under the MMG, while the
      second patient underwent implantation of a modification of Auro Kpro with a
      longer optical stem (LVP Kpro) exposed through the MMG. Both patients maintained
      a visual acuity of 20/20, N6 at 15 months post-implantation. The first patient
      needed repeated mucosal trimming because of mucosal overgrowth; while in the
      second patient, mucosal overgrowth did not occur. This report highlights the
      innovative and successful use of Boston type 1-based keratoprosthesis (Auro Kpro)
      and its modification (LVP Kpro) in completely dry and keratinised post-SJS eyes. 

PMID- 24663250
TI  - Sporadic Creutzfeldt-Jakob disease (sCJD) with asymmetric findings.
AB  - We report a case of a patient with probable Creutzfeldt-Jakob disease (CJD) who
      had psychiatric manifestation in the form of withdrawn depressive behaviour at
      the onset, followed by rapidly progressive ataxia, parkinsonism, mutism and
      cognitive decline with generalised asynchronous multifocal myoclonic jerks. His
      EEG exhibited focal (lateralised) periodic triphasic sharp waves on the
      background of generalised delta slowing, which later on became more generalised.
      MRI of the brain showed hyperintensity in basal ganglia with cortical ribbon sign
      in bilateral frontal region. Clinical course showed progressive deterioration to
      an akinetic-abulic stage. He died 2 months after the onset of symptoms. 

PMID- 24663251
TI  - MDCT demonstration of jejunal angiodysplasia: an uncommon cause of lower
      gastrointestinal haemorrhage.

PMID- 24663252
TI  - Central vein stenosis masquerading as venous thrombosis.

PMID- 24663253
TI  - Serum vitamin D levels may not reflect tissue-level vitamin D in sarcoidosis.
AB  - Hypercalcemia in sarcoidosis is due to three mechanistic reasons: (1) systemic
      conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the enzyme 1
      alpha hydroxylase produced by activated monocyte/macrophage system, (2)
      production of parathormone-related peptide (PTHrP) by the sarcoid granuloma, (3)
      tissue-level conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by 1
      alphahydroxylase produced by local monocyte/macrophage system in the sarcoid
      granuloma. We report two cases of one proposed mechanism of hypercalcaemia in
      sarcoidosis (mechanism 3). Both individuals presented with sarcoidosis and 25
      hydroxyvitamin D deficiency and developed symptomatic hypercalcaemia with vitamin
      D replacement. Given their low serum parathormone and parathormone-related
      peptide levels, low serum 25-hydroxy vitamin D and normal serum 1,25
      dihydroxyvitamin D, the systemic 25-hydroxy vitamin D deficiency may not have
      reflected an increased activity of vitamin D at the local granulomatous tissue
      level. 

PMID- 24663254
TI  - Giant hand lipoma invaginating the thenar muscles.

PMID- 24663256
TI  - Absolute surface metrology with a phase-shifting interferometer for
      incommensurate transverse spatial shifts.
AB  - We consider the detailed implementation and practical utility of a novel absolute
      optical metrology scheme recently proposed for use with a phase-shifting
      interferometer (PSI). This scheme extracts absolute phase differences between
      points on the surface of the optic under test by differencing phase maps made
      with slightly different transverse spatial shifts of that optic. These absolute
      phase (or height) differences, which for single-pixel shifts are automatically
      obtained in the well-known Hudgin geometry, yield the underlying absolute surface
      map by standard wavefront reconstruction techniques. The PSI by itself maps
      surface height only relative to that of a separate reference optic known or
      assumed to be flat. In practice, even relatively high-quality (and expensive)
      transmission flats or spheres used to reference a PSI are flat or spherical only
      to a few dozen nanometers peak to valley (P-V) over typical 4 in. apertures. The
      new technique for removing the effects of the reference surface is in principle
      accurate as well as simple, and may represent a significant advance in optical
      metrology. Here it is shown that transverse shifts need not match the pixel size;
      somewhat counterintuitively, the single-pixel spatial resolution of the PSI is
      retained even when transverse shifts are much coarser. Practical considerations
      for shifts not necessarily commensurate with pixel size, and broader
      applications, are discussed.

PMID- 24663257
TI  - Improved data pages for an interference-based cryptosystem.
AB  - In this paper, we propose a novel input wave front modulation method to enhance
      the security level of a Mach-Zender interferometer-based Fourier encryption
      system. The input data is encoded in the two wave fronts propagated in the arms
      of the interferometer. Both arms contain a 4f setup, and two independent Fourier
      keys are used to encrypt these wave fronts. During decryption the encrypted wave
      fronts are propagated through the interferometer. In the case when correct
      Fourier keys are used for decryption, the reconstructed data page is shown by the
      interference pattern of the output. We propose a method to synthesize two phase
      modulated input images for this cryptosystem. The modulation method has a user
      defined phase parameter. We prove that the security level of the proposed
      cryptosystem can be significantly improved compared with previous solutions, by
      using an optimally chosen phase parameter. 

PMID- 24663255
TI  - Reappraisal of routine oral care with chlorhexidine gluconate for patients
      receiving mechanical ventilation: systematic review and meta-analysis.
AB  - IMPORTANCE: Regular oral care with chlorhexidine gluconate is standard of care
      for patients receiving mechanical ventilation in most hospitals. This policy is
      predicated on meta-analyses suggesting decreased risk of ventilator-associated
      pneumonia, but these meta-analyses may be misleading because of lack of
      distinction between cardiac surgery and non-cardiac surgery studies, conflation
      of open-label vs double-blind investigations, and insufficient emphasis on
      patient-centered outcomes such as duration of mechanical ventilation, length of
      stay, and mortality. OBJECTIVE: To evaluate the impact of routine oral care with
      chlorhexidine on patient-centered outcomes in patients receiving mechanical
      ventilation. DATA SOURCES: PubMed, Embase, CINAHL, and Web of Science from
      inception until July 2013 without limits on date or language. STUDY SELECTION:
      Randomized clinical trials comparing chlorhexidine vs placebo in adults receiving
      mechanical ventilation. Of 171 unique citations, 16 studies including 3630
      patients met inclusion criteria. DATA EXTRACTION AND SYNTHESIS: Eligible trials
      were independently identified, evaluated for risk of bias, and extracted by 2
      investigators. Differences were resolved by consensus. We stratified studies into
      cardiac surgery vs non-cardiac surgery and open-label vs double-blind
      investigations. Eligible studies were pooled using random-effects meta-analysis.
      MAIN OUTCOMES AND MEASURES: Ventilator-associated pneumonia, mortality, duration
      of mechanical ventilation, intensive care unit and hospital length of stay,
      antibiotic prescribing. RESULTS: There were fewer lower respiratory tract
      infections in cardiac surgery patients randomized to chlorhexidine (relative risk
      [RR], 0.56 [95% CI, 0.41-0.77]) but no significant difference in ventilator
      associated pneumonia risk in double-blind studies of non-cardiac surgery patients
      (RR, 0.88 [95% CI, 0.66-1.16]). There was no significant mortality difference
      between chlorhexidine and placebo in cardiac surgery studies (RR, 0.88 [95% CI,
      0.25-2.14]) and nonsignificantly increased mortality in non-cardiac surgery
      studies (RR, 1.13 [95% CI, 0.99-1.29]). There were no significant differences in
      mean duration of mechanical ventilation or intensive care length of stay. Data on
      hospital length of stay and antibiotic prescribing were limited. CONCLUSIONS AND
      RELEVANCE: Routine oral care with chlorhexidine prevents nosocomial pneumonia in
      cardiac surgery patients but may not decrease ventilator-associated pneumonia
      risk in non-cardiac surgery patients. Chlorhexidine use does not affect patient
      centered outcomes in either population. Policies encouraging routine oral care
      with chlorhexidine for non-cardiac surgery patients merit reevaluation.

PMID- 24663259
TI  - Advanced sine wave modulation of continuous wave laser system for atmospheric
      CO(2) differential absorption measurements.
AB  - In this theoretical study, modulation techniques are developed to support the
      Active Sensing of CO<sub>2</sub> Emissions over Nights, Days, and Seasons
      (ASCENDS) mission. A continuous wave (CW) lidar system using sine waves modulated
      by maximum length (ML) pseudo-noise (PN) codes is described for making
      simultaneous online/offline differential absorption measurements. Amplitude and
      phase-shift keying (PSK) modulated intensity modulation (IM) carriers, in
      addition to a hybrid-pulse technique are investigated, which exhibit optimal
      autocorrelation properties. A method is presented to bandwidth limit the ML
      sequence based on a filter implemented in terms of Jacobi theta functions, which
      does not significantly degrade the resolution or introduce sidelobes as a means
      of reducing aliasing and IM carrier bandwidth. 

PMID- 24663258
TI  - Analysis of cross-sectional image filters for evaluating nonaveraged optical
      microangiography images.
AB  - Optical microangiography (OMAG) is a method that enables the noninvasive
      extraction of blood vessels within biological tissues. OMAG B-frames are prone to
      noise; therefore, techniques such as B-frame averaging have been applied to
      reduce these effects. A drawback of this method is that the total acquisition
      time and amount of data collected are increased; hence, the data are susceptible
      to motion artifacts and decorrelation. In this paper we propose using an image
      filter on a nonaveraged OMAG B-frame to reduce its noise. Consequently, B-frames
      comparable to the averaged OMAG B-frame are obtained, while reducing the total
      acquisition and processing time. The method is tested with two different systems,
      a high-resolution spectral domain and a relatively low-resolution swept-source
      optical coherence tomography system. It is demonstrated that the weighted average
      filter produces the lowest B-frame error; however, all filters produce comparable
      results when quantifying the en face projection view image. 

PMID- 24663260
TI  - Simple analytical model for low-frequency frequency-modulation noise of
      monolithic tunable lasers.
AB  - We employ simple analytical models to construct the entire frequency-modulation
      (FM)-noise spectrum of tunable semiconductor lasers. Many contributions to the
      laser FM noise can be clearly identified from the FM-noise spectrum, such as
      standard Weiner FM noise incorporating laser relaxation oscillation, excess FM
      noise due to thermal fluctuations, and carrier-induced refractive index
      fluctuations from stochastic carrier generation in the passive tuning sections.
      The contribution of the latter effect is identified by noting a correlation
      between part of the FM-noise spectrum with the FM-modulation response of the
      passive sections. We pay particular attention to the case of widely tunable
      lasers with three independent tuning sections, mainly the sampled-grating
      distributed Bragg reflector laser, and compare with that of a distributed
      feedback laser. The theoretical model is confirmed with experimental
      measurements, with the calculations of the important phase-error variance
      demonstrating excellent agreement. 

PMID- 24663261
TI  - Phase-stepping technique for highly sensitive microscopic surface plasmon
      resonance biosensor.
AB  - In this paper, the phase-stepping technique is applied to improve a phase
      sensitive surface plasmon resonance biosensor based on differential
      interferometry between focused radially polarized and azimuthally polarized
      cylindrical vector beams. Detailed analysis is presented for the phase-stepping
      method, and the least squares unwrapping algorithm is employed to detect the
      phase distribution in correspondence to the refractive index of sample.
      Benefiting from the phase-stepping technique, both the measurement speed and
      sensitivity are improved significantly. The proposed sensor maintains high
      sensitivity of 9.4*10<sup>-7</sup>  RIU/1 degrees  and a wide dynamic range of
      0.35 RIU simultaneously. Furthermore, the real-time binding reaction process of
      bovine serum albumin with antibody is monitored to verify the system for
      potential biological applications. 

PMID- 24663262
TI  - Near-self-imaging cavity for three-mode optoacoustic parametric amplifiers using
      silicon microresonators.
AB  - Three-mode optoacoustic parametric amplifiers (OAPAs), in which a pair of photon
      modes are strongly coupled to an acoustic mode, provide a general platform for
      investigating self-cooling, parametric instability and very sensitive
      transducers. Their realization requires an optical cavity with tunable transverse
      modes and a high quality-factor mirror resonator. This paper presents the design
      of a table-top OAPA based on a near-self-imaging cavity design, using a silicon
      torsional microresonator. The design achieves a tuning coefficient for the
      optical mode spacing of 2.46  MHz/mm. This allows tuning of the mode spacing
      between amplification and self-cooling regimes of the OAPA device. Based on
      demonstrated resonator parameters (frequencies ~400  kHz and quality-factors
      ~7.5*10(5) we predict that the OAPA can achieve parametric instability with 1.6
      MUW of input power and mode cooling by a factor of 1.9*10(4) with 30 mW of input
      power.

PMID- 24663263
TI  - Optical properties and laser damage threshold of HfO(2)-SiO(2) mixed composite
      thin films.
AB  - HfO(2)-SiO(2) mixed composite thin films have been deposited on fused silica
      substrate by co-evaporation of HfO(2) and SiO(2) through the reactive electron
      beam evaporation technique. The composition-dependent refractive index and the
      absorption coefficient have been analyzed using different effective medium
      approximation (EMA) models in order to evaluate the suitability of these models
      for such mixed composite thin films. The discrepancies between experimentally
      determined and EMA-computed values are explained through microstructural and
      morphological evolutions observed in these mixed composite films. Finally, the
      dependence of the laser damage threshold as a function of silica content has been
      investigated, and the improved laser-induced damage threshold for films having
      more than 80% silica content has been explained through the defect-assisted
      multiphoton ionization process.

PMID- 24663264
TI  - Common characteristics shared by different differential phase contrast imaging
      methods.
AB  - There are many variations of differential phase contrast imaging methods.
      Although these imaging methods are different in configuration, they are alike in
      imaging by extracting differential phase information through the evaluation of
      the refraction angles. In this paper, we investigate common characteristics
      shared by various different differential phase contrast imaging methods. 

PMID- 24663265
TI  - Numerical simulation of the optical characteristics of autostereoscopic displays
      that have an aspherical lens array with a slanted angle.
AB  - We developed a 3D simulation model describing the optical phenomena on a slanted
      lenticular surface with aspherical lenses for autostereoscopic displays and
      analyzed the optical behavior of the multiview autostereoscopic display under
      actual design conditions by using a 3D simulation model. Optical characteristics,
      such as 3D crosstalk and 3D luminance differences, are obtained from the
      simulation of the light distribution for the multiview autostereoscopic displays
      with slated angles of 0.0 degrees , 9.46 degrees , 12.59 degrees , and 14.04
      degrees . By investigating the effect of the conic constant of an aspherical lens
      surface on the 3D crosstalk and the 3D luminance differences for given several
      design conditions, we find the optimal values of the conic constant for slanted
      angles of 0.0 degrees  and 9.46 degrees  in order to minimize the 3D crosstalk
      and the 3D luminance difference. From these results, we think that our simulation
      model is very useful for designing the lens array to optimize the optical
      characteristics of autostereoscopic displays. 

PMID- 24663266
TI  - Selective excitation of microring resonances using a pulley-coupling structure.
AB  - We explore the selective excitation of resonances in microring resonators with a
      pulley-coupling structure. Due to the wavelength dispersion of coupling
      coefficient, only the resonances near critical coupling exhibit pronounced sharp
      notches in the transmission spectrum. Experimental results show that the
      resonance extinction ratio is a strong function of wavelength. Theoretical
      analysis further predicts that it is possible to highly suppress the neighboring
      resonances to effectively enlarge the free spectral range (FSR). With a proper
      design, the FSR can be increased by more than 1 order for a 10 MUm radius
      microring resonator using the pulley-coupling structure. 

PMID- 24663267
TI  - Effects of bonding layer on the available strain measuring range of fiber Bragg
      gratings.
AB  - Stress-induced birefringence can lead to distortion in the reflection spectra of
      fiber Bragg grating (FBG) sensors, thereby resulting in the loss of accuracy and
      stability of strain measurements. The bonding layer is a direct factor in
      producing stress birefringence within FBGs. To assess the impacts quantitatively,
      a theoretical model that links the bonding layer and the reflection spectrum was
      established. At the same time, the finite element method, based on the
      theoretical model, was used to study the relationships between characteristics of
      the bonding layer and reflection spectrum in detail. The analytical results
      indicate that high elastic modulus and mismatched Poisson's ratio of bonding
      layer decrease the available strain measuring range of FBGs remarkably, and that
      unreasonable geometric parameters of the bonding layer should be avoided. In
      addition, a validation experiment was conducted and experimental results proved
      the prediction of the theoretical analysis. It can be concluded from the results
      that the bonding layer is the major limiting factor for the application of
      surface-bonded FBG sensors in large strain measurements. The bonding materials
      and bonding processes used in producing FBG sensors deserve serious
      consideration. 

PMID- 24663268
TI  - Self-mode-locked 2 MUm Tm(3+)-doped double-clad fiber laser with a simple linear
      cavity.
AB  - We demonstrate the self-mode-locking operation of a thulium (Tm)-doped fiber
      laser (TDFL) with a simple linear cavity. Since the laser cavity does not include
      any specific mode-locker, we experimentally investigate and analyze the self-mode
      locking mechanism. The mode-locking operation is attributed to the combination of
      the self-phase modulation effect and the weak saturable absorption of the high
      concentration Tm-doped fiber. The mode-locked TDFL operates at a central
      wavelength of 1985.5 nm with the 3 dB spectral linewidth of 0.18 nm. The self
      mode-locking generates a large pulse energy of 32.7 nJ with a pulsed repetition
      rate of 2.05 MHz and is stable with a radio-frequency signal-to-noise ratio of
      more than 54 dB. To the best of our knowledge, it is the first demonstration of a
      2 MUm Tm-doped fiber laser mode-locked by such technique. 

PMID- 24663269
TI  - Energy-phase coupling inside sapphire-based f-2f nonlinear interferometers from
      800 to 1940 nm.
AB  - Energy-phase coupling inside f-2f nonlinear interferometers poses stringent
      limits on the tolerable pulse-to-pulse energy fluctuations of phase stable laser
      systems. Here we report a coupling coefficient of -220+/-20  mrad per 1% energy
      increase at 800 nm. We also report coefficients from +320 to +820  mrad per 1%
      energy increase in the 1140-1550 nm (signal) range. Finally, we report
      coefficients from -180 to +30  mrad per 1% energy variation in the 1636-1940 nm
      range. 

PMID- 24663270
TI  - Flattop pulse generation based on the combined action of active mode locking and
      nonlinear polarization rotation.
AB  - A pulse-width-tunable 10 GHz flattop pulse (FTP) train is generated based on the
      combined action of active mode locking and nonlinear polarization rotation pulse
      shaping. Although the setup was previously used for other applications, the
      mechanism of FTP generation based on it is first analyzed and confirmed in the
      experiment. An FTP with pulse width tunable from 12 to 20 ps by changing
      polarization controllers is generated within the wavelength tuning range of 20
      nm. The generated pulse reveals good stability, with the side mode suppression
      ratio of 65 dB, timing jitter of 92 fs, and amplitude fluctuation of 0.36%. 

PMID- 24663271
TI  - Sol-gel synthesized far-red chromium-doped garnet phosphors for phosphor
      conversion light-emitting diodes that meet the photomorphogenetic needs of
      plants.
AB  - We report the sol-gel synthesis and characterization of far-red garnet phosphors
      Gd(3)Ga(5)O(12) (GGG:Cr), Y(3)Ga(5)O(12) (YGG:Cr), Lu(3)Ga(5)O(12) (LGG:Cr), and
      Gd(3)Sc(2)Ga(3)O(12) (GSGG:Cr) doped with different chromium (III) concentration
      (3, 5, and 8 mol. %). The morphological and luminescence properties of the
      phosphors annealed at different temperatures (1000 degrees C, 1300 degrees C,
      1400 degrees C, and 1500 degrees C) were examined using x-ray diffraction,
      scanning electron microscopy, photoluminescence (PL), and PL excitation (PLE)
      spectroscopy, and by the measurements of diffuse reflection, PL internal quantum
      efficiency (QE), and PL decay time. The PLE spectra of the samples were found to
      peak at around 450 nm depending on the host, and luminescence was observed in the
      region of 700-760 nm. The QE was found to strongly depend on doping concentration
      and calcination temperature, and the PL decay exhibited biexponential behavior.
      The investigated far-red garnet phosphors, in particular GGG:Cr and YGG:Cr, show
      a potential for use in phosphor-converted light-emitting diodes that meet the
      photomorphogenetic needs of plants.

PMID- 24663272
TI  - Seidel aberrations of the Gabor superlens.
AB  - Equations are presented for the third-order Seidel aberrations of the Gabor
      superlens (GSL) as a function of microtelescope channel position within the
      aperture array. To reveal the origin and form of increasing aberration with
      channel height, Seidel coefficients are derived as a function of the accumulating
      pitch difference between the lens arrays and the aberrations present in the
      centered channel. Two- and three-element Gabor lenses are investigated and their
      aberrations are expressed as a function of first-order design parameters. The
      derived theory is then compared to a real ray trace simulation to demonstrate the
      accuracy of third-order aberration theory to predict GSL image quality. 

PMID- 24663274
TI  - Vibration detection by observation of speckle patterns.
AB  - When laser light illuminates a rough surface it is scattered into a speckle
      pattern that is strongly dependent on the surface geometry. Here, we show that it
      is possible to sense surface vibrations by measuring signal variations from a
      single pixel detector that collects a small portion of the scattered light. By
      carefully tuning the probing laser beam size and the detector's aperture it was
      possible to record a good quality signal in the acoustic band. This approach
      eliminates the need for an interferometer and thus opens the door to the
      possibility of detecting vibrations at distances of few hundreds of meters. 

PMID- 24663273
TI  - Binary pattern deflectometry.
AB  - Deflectometry is widely used to accurately calculate the slopes of any specular
      reflective surface, ranging from car bodies to nanometer-level mirrors. This
      paper presents a new deflectometry technique using binary patterns of increasing
      frequency to retrieve the surface slopes. Binary Pattern Deflectometry allows
      almost instant, simple, and accurate slope retrieval, which is required for
      applications using mobile devices. The paper details the theory of this
      deflectometry method and the challenges of its implementation. Furthermore, the
      binary pattern method can also be combined with a classic phase-shifting method
      to eliminate the need of a complex unwrapping algorithm and retrieve the absolute
      phase, especially in cases like segmented optics, where spatial algorithms have
      difficulties. Finally, whether it is used as a stand-alone or combined with phase
      shifting, the binary patterns can, within seconds, calculate the slopes of any
      specular reflective surface. 

PMID- 24663275
TI  - High-quality fiber microaxicons fabricated by a modified chemical etching method
      for laser focusing and generation of Bessel-like beams.
AB  - The fabrication method of the high-quality fiber microaxicons (FMAs) on the
      endface of the optical fiber was developed. Using several types of the
      commercially available optical fibers we experimentally demonstrated the
      fabrication of a high-quality FMA focusing a laser beam into a tiny spot with a
      FWHM~0.6lambda and Bessel-like field distribution. It was also demonstrated that
      choosing the appropriate chemical composition of the etching solution makes it
      possible to change the shape of the FMA tip from conical to hemispherical. This
      allows one to change the spatial distribution of the output laser beam, which can
      represent both the Bessel-like beam with a depth of focus of up to 49lambda and a
      very tiny focal spot close to the diffraction limit size. Experimentally measured
      focusing characteristics of the fabricated FMAs obtained using a homemade
      collection-mode scanning near-field optical microscope setup demonstrate good
      agreement with numerical simulations based on the 3D finite-difference time
      domain simulations. 

PMID- 24663276
TI  - Long-period cascaded fiber taper filters.
AB  - Fiber filters based on periodic cascaded tapered fiber sections are demonstrated.
      The filters consist of up to seven tapered sections separated periodically by
      more than 3 mm from center to center, with nominal tapered sections of 1  mm*1 
      mm*1  mm longitudinal dimensions. The transmission spectrum consists of discrete
      notches, resembling those observed in long-period fiber gratings, which differs
      from the observed spectrum in Mach-Zender interferometers based on cascaded
      tapers. Its sensitivity to external perturbations, such as refractive index or
      mechanical stress, made the device potentially very useful as a sensor or tunable
      filter. 

PMID- 24663277
TI  - Moire interferometry with high alignment resolution in proximity lithographic
      process.
AB  - Moire interferometry is widely used as the precise metrology in many science and
      engineering fields. The schemes of moires-based interferometry adopting
      diffraction gratings are presented in this paper for applications in a proximity
      lithographic system such as wafer-mask alignment, the in-plane twist angle
      adjustment, and tilts remediation. For the sake of adjustment of lateral offset
      as well as the tilt and in-plane twist angle, schemes of the (m,-m) and (m,0)
      moire interferometry are explored, respectively. Fundamental derivation of the
      moire interferometry and schemes for related applications are provided. Three
      pairs of gratings with close periods are fabricated to form the composite
      grating. And experiments are performed to confirm the moire interferometry for
      related applications in our proximity lithographic system. Experimental results
      indicate that unaligned lateral offset is detectable with resolution at the
      nanometer level, and the tilt and in-plane twist angle between wafer and mask
      could be manually decreased down to the scope of 10(-3) and 10(-4)  rad,
      respectively.

PMID- 24663278
TI  - Improved digital image correlation for in-plane displacement measurement.
AB  - Electronic speckle photography (ESP) for in-plane displacement (IPD) and
      deformation measurements is well known with its more modern form, digital image
      correlation (DIC). Two speckle images of an optically rough surface before and
      after deformation, called reference and test images, are recorded and processed
      for IPD or deformation measurement of the test image with respect to the
      reference image. The reliability of ESP in measurements depends strongly on the
      postprocessing of the two images by DIC, which we have referred to as
      conventional DIC. In this paper, we are proposing a small but useful modification
      in the existing DIC methods by introducing some additional steps, which
      drastically improves the results obtained with the existing techniques. The
      modification to the conventional DIC method has been referred to as modified DIC.
      Computer-simulated and experimental results have been presented to validate the
      superiority of modified DIC over conventional DIC methods. 

PMID- 24663279
TI  - Analysis of backscattering characteristics of objects for remote laser voice
      acquisition.
AB  - This study is focused on numerical simulation analysis and experimental study
      regarding the influence of backscattering characteristics of objects for long
      range laser voice acquisition. Based on theoretical analysis, three parameters,
      including surface roughness of an object, incident angle, and refractive index,
      which will influence the performance of remote scattered reflection laser
      interference voice acquisition, are investigated and analyzed. After analysis and
      simulation, an experimental system is set up to demonstrate the influence of
      backscattering characteristics of an object. The results show that the restored
      amplitude of a voice signal decreases gradually, corresponding to an increase of
      surface roughness from 0.4 to 12.5 MUm; the incident angle of the measured laser
      shall reside between 57.32 deg (1 rad) and -57.32  deg (-1  rad); the optimal
      incident angle is 0 deg for all kinds of objects; and the metal object is a
      better choice of material selection. In addition, the restored amplitude of a
      voice signal rises with the attenuation coefficient of metal increasing. It also
      increases with the refractive index for a nonmetallic object. Comparing a metal
      to a nonmetallic object, the amplitude of voice signal varies significantly. 

PMID- 24663280
TI  - Multiple-wavelength-scanning-based phase unwrapping method for digital
      holographic microscopy.
AB  - A phase unwrapping approach based on multiple-wavelength scanning is presented
      for digital holographic microscopy. It unwrapped the ambiguous phase image layer
      by layer by synthesizing the extracted continuous components from a set of
      multiple phase images obtained by varying the optical wavelength, where the
      discontinuities occur at different places and the phase speckle noise presents
      various distributions in state. The total time for data acquisition is
      approximately 22 min for 10 wavelengths. The simulation and experimental results
      demonstrate that the proposed method has a more accurate calculation and better
      counteraction of phase noise compared with those of previously reported
      approaches. In addition, the wrapped phase image of the object containing the
      steps has also been unwrapped successfully. 

PMID- 24663281
TI  - Sharp and rectified imaging of plane test objects in diffractive grazing
      incidence interferometers.
AB  - Fine-ground plane surfaces can be interferometrically tested in grazing incidence
      with laser illumination in the visible. Since the roughness of the surfaces is in
      the micrometer-range, the incidence angle of the probing wave front is very close
      to 90 degrees , causing a strong anamorphic distortion of the length of the test
      sample on an imaging detector. In contrast to this the width of the sample
      remains undistorted in the image plane. Here, the case of a diffractive grazing
      incidence solution will be discussed. In particular, the rectification of the
      anamorphic distortion combined with sharp imaging of the whole length of the test
      sample will be described together with solutions for matching the illuminating
      and imaging beam cross section to the lateral extension of the sample. 

PMID- 24663282
TI  - On the nature of Acket's characteristic parameter C in semiconductor lasers.
AB  - Quasi-static interferometric signals in lasers under feedback arise from slowly
      varying perturbations of the intracavity electric field resulting from the
      reinjection of a portion of the emitted field into the cavity. Such
      interferometric signals are well described by the steady-state solution to the
      Lang-Kobayashi rate equation model. We give an exact series expansion for this
      steady-state solution that shows precisely how Acket's characteristic parameter C
      and Henry's linewidth enhancement factor alpha influence such signals. We show
      how the series coefficients can be extracted easily and explain how to determine
      C and alpha directly from them. Moreover, we draw a precise analogy between self
      mixing and FM signals, showing that C plays exactly the same role in self-mixing
      as the modulation index does in FM. 

PMID- 24663283
TI  - Spectral and temporal properties of optical signals with multiple sinusoidal
      phase modulations.
AB  - Optical signals generated by multiple sinusoidal temporal phase modulations
      (multi-FMs) applied to a monochromatic field are studied from the viewpoint of
      their optical spectrum and temporal modulations arising from spectral
      impairments. Statistical analysis based on the central limit theorem shows that
      the signals' optical spectrum converges to a normal distribution as the number of
      modulations increases, allowing one to predict the frequency range containing a
      given fraction of the total energy with the associated cumulative density
      function. The conversion of frequency modulation to amplitude modulation is
      analyzed and simulated for arbitrary multi-FM signals. These developments are of
      theoretical and practical importance for high-energy laser systems, where optical
      pulses are phase modulated in the front end to smooth out the on-target beam
      profile and prevent potentially catastrophic damage to optical components. 

PMID- 24663284
TI  - 99mTcO4--, auger-mediated thyroid stunning: dosimetric requirements and
      associated molecular events.
AB  - Low-energy Auger and conversion electrons deposit their energy in a very small
      volume (a few nm3) around the site of emission. From a radiotoxicological point
      of view the effects of low-energy electrons on normal tissues are largely
      unknown, understudied, and generally assumed to be negligible. In this context,
      the discovery that the low-energy electron emitter, 99mTc, can induce stunning on
      primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated
      in vivo, this observation suggests that a radioisotope as commonly used in
      nuclear medicine as 99mTc may significantly influence thyroid physiology. The
      aims of this study were to determine whether 99mTc pertechnetate (99mTcO4-) is
      capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of
      99mTcO4- required to induce this stunning, and to analyze the biological events
      associated/concomitant with this effect. Our results show that 99mTcO4--mediated
      thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the
      absorbed dose in the thyroid required to obtain a significant stunning effect is
      in the range of 20 Gy. This effect is associated with a reduced level of
      functional Na/I symporter (NIS) protein, with no significant cell death. It is
      reversible within a few days. At the cellular and molecular levels, a decrease in
      NIS mRNA, the generation of double-strand DNA breaks, and the activation of the
      p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore,
      induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of
      at least 20 Gy, a level unlikely to be encountered in clinical practice.
      Nevertheless this report presents an unexpected effect of low-energy electrons on
      a normal tissue in vivo, and provides a unique experimental setup to understand
      the fine molecular mechanisms involved in their biological effects. 

PMID- 24663286
TI  - Suppression of phase coarsening in immiscible, co-continuous polymer blends under
      high temperature quiescent annealing.
AB  - The properties of polymer blends greatly depend on the morphologies formed during
      processing, and the thermodynamic non-equilibrium nature of most polymer blends
      makes it important to maintain the morphology stability to ensure the performance
      stability of structural materials. Herein, the phase coarsening of co-continuous,
      immiscible polyamide 6 (PA6)-acrylonitrile-butadiene-styrene (ABS) blends in the
      melt state was studied and the effect of introduction of nano-silica particles on
      the stability of the phase morphology was examined. It was found that the PA6-ABS
      (50/50 w) blend maintained the co-continuous morphology but coarsened severely
      upon annealing at 230  degrees C. The coarsening process could be divided into
      two stages: a fast coarsening process at the initial stage of annealing and a
      second coarsening process with a relatively slow coarsening rate later. The
      reduction of the coarsening rate can be explained from the reduction of the
      global curvature of the interface. With the introduction of nano-silica, the
      composites also showed two stages of coarsening. However, the coarsening rate was
      significantly decreased and the phase morphology was stabilized. Rheological
      measurements indicated that a particle network structure was formed when the
      concentration of nano-silica particles was beyond 2 wt%. The particle network
      inhibited the movement of molecular chains and thus suppressed the coarsening
      process. 

PMID- 24663285
TI  - Impact of cigarette smoke on the human and mouse lungs: a gene-expression
      comparison study.
AB  - Cigarette smoke is well known for its adverse effects on human health, especially
      on the lungs. Basic research is essential to identify the mechanisms involved in
      the development of cigarette smoke-related diseases, but translation of new
      findings from pre-clinical models to the clinic remains difficult. In the present
      study, we aimed at comparing the gene expression signature between the lungs of
      human smokers and mice exposed to cigarette smoke to identify the similarities
      and differences. Using human and mouse whole-genome gene expression arrays,
      changes in gene expression, signaling pathways and biological functions were
      assessed. We found that genes significantly modulated by cigarette smoke in
      humans were enriched for genes modulated by cigarette smoke in mice, suggesting a
      similar response of both species. Sixteen smoking-induced genes were in common
      between humans and mice including six newly reported to be modulated by cigarette
      smoke. In addition, we identified a new conserved pulmonary response to cigarette
      smoke in the induction of phospholipid metabolism/degradation pathways. Finally,
      the majority of biological functions modulated by cigarette smoke in humans were
      also affected in mice. Altogether, the present study provides information on
      similarities and differences in lung gene expression response to cigarette smoke
      that exist between human and mouse. Our results foster the idea that animal
      models should be used to study the involvement of pathways rather than single
      genes in human diseases. 

PMID- 24663287
TI  - Active raster scanning with carbon ions: reirradiation in patients with recurrent
      skull base chordomas and chondrosarcomas.
AB  - PURPOSE: To evaluate the safety and efficacy of reirradiation with carbon ions in
      patients with relapse of skull base chordoma and chondrosarcoma. PATIENTS AND
      METHODS: Reirradiation with carbon ions was performed on 25 patients with locally
      recurrent skull base chordoma (n = 20) or chondrosarcoma (n = 5). The median time
      between the last radiation exposure and the reirradiation with carbon ions was 7
      years. In the past, 23 patients had been irradiated once, two patients twice.
      Reirradiation was delivered using the active raster scanning method. The total
      median dose was 51.0 GyE carbon ions in a weekly regimen of five to six fractions
      of 3 GyE. Local progression-free survival (LPFS) was evaluated using the Kaplan
      Meier method; toxicity was evaluated using the NCI Common Terminology Criteria
      for Adverse Events (CTCAE v.4.03). RESULTS: The treatment could be finished in
      all patients without interruption. In 80% of patients, symptom control was
      achieved after therapy. The 2-year-LPFS probability was 79.3%. A PTV volume of <
      100 ml or a total dose of > 51 GyE was associated with a superior local control
      rate. The therapy was associated with low acute toxicity. One patient developed
      grade 2 mucositis during therapy. Furthermore, 12% of patients had tympanic
      effusion with mild hypacusis (grade 2), while 20% developed an asymptomatic
      temporal lobe reaction after treatment (grade 1). Only one patient showed a grade
      3 osteoradionecrosis. CONCLUSION: Reirradiation with carbon ions is a safe and
      effective method in patients with relapsed chordoma and chondrosarcoma of the
      skull base.

PMID- 24663288
TI  - Stereotactic radiosurgery for newly diagnosed brain metastases: comparison of
      three dose levels.
AB  - BACKGROUND AND PURPOSE: Three doses were compared for local control of irradiated
      metastases, freedom from new brain metastases, and survival in patients receiving
      stereotactic radiosurgery (SRS) alone for one to three newly diagnosed brain
      metastases. PATIENTS AND METHODS: In all, 134 patients were assigned to three
      groups according to the SRS dose given to the margins of the lesions: 13-16 Gy (n
      = 33), 18 Gy (n = 18), and 20 Gy (n = 83). Additional potential prognostic
      factors were evaluated: age (<= 60 vs. > 60 years), gender, Karnofsky Performance
      Scale score (70-80 vs. 90-100), tumor type (non-small-cell lung cancer vs.
      melanoma vs. others), number of brain metastases (1 vs. 2-3), lesion size (< 15
      vs. >= 15 mm), extracranial metastases (no vs. yes), RPA class (1 vs. 2), and
      interval of cancer diagnosis to SRS (<= 24 vs. > 24 months). RESULTS: For 13-16
      Gy, 18 Gy, and 20 Gy, the 1-year local control rates were 31, 65, and 79%,
      respectively (p < 0.001). The SRS dose maintained significance on multivariate
      analysis (risk ratio: 2.25; 95% confidence interval: 1.56-3.29; p < 0.001). On
      intergroup comparisons of local control, 20 Gy was superior to 13-16 Gy (p <
      0.001) but not to 18 Gy (p = 0.12); 18 Gy showed a strong trend toward better
      local control when compared with 13-16 Gy (p = 0.059). Freedom from new brain
      metastases (p = 0.57) and survival (p = 0.15) were not associated with SRS dose
      in the univariate analysis. CONCLUSION: SRS doses of 18 Gy and 20 Gy resulted in
      better local control than 13-16 Gy. However, 20 Gy and 18 Gy must be compared
      again in a larger cohort of patients. Freedom from new brain metastases and
      survival were not associated with SRS dose.

PMID- 24663289
TI  - A prediction model for 5-year cardiac mortality in patients with chronic heart
      failure using 123I-metaiodobenzylguanidine imaging.
AB  - PURPOSE: Prediction of mortality risk is important in the management of chronic
      heart failure (CHF). The aim of this study was to create a prediction model for 5
      year cardiac death including assessment of cardiac sympathetic innervation using
      data from a multicenter cohort study in Japan. METHODS: The original pooled
      database consisted of cohort studies from six sites in Japan. A total of 933 CHF
      patients who underwent (123)I-metaiodobenzylguanidine (MIBG) imaging and whose 5
      year outcomes were known were selected from this database. The late MIBG heart-to
      mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox
      proportional hazard and logistic regression analyses were used to select
      appropriate variables for predicting 5-year cardiac mortality. The formula for
      predicting 5-year mortality was created using a logistic regression model.
      RESULTS: During the 5-year follow-up, 205 patients (22 %) died of a cardiac event
      including heart failure death, sudden cardiac death and fatal acute myocardial
      infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis
      selected four parameters, including New York Heart Association (NYHA) functional
      class, age, gender and left ventricular ejection fraction, without HMR (model 1)
      and five parameters with the addition of HMR (model 2). The net reclassification
      improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR
      and its inclusion was most effective in the downward reclassification of low-risk
      patients. Nomograms for predicting 5-year cardiac mortality were created from the
      five-parameter regression model. CONCLUSION: Cardiac MIBG imaging had a
      significant additive value for predicting cardiac mortality. The prediction
      formula and nomograms can be used for risk stratifying in patients with CHF.

PMID- 24663290
TI  - Phosphine catalysis of allenes with electrophiles.
AB  - Nucleophilic phosphine catalysis of allenes with electrophiles is one of the most
      powerful and straightforward synthetic strategies for the generation of highly
      functionalized carbocycle or heterocycle structural motifs, which are present in
      a wide range of bioactive natural products and medicinally important substances.
      The reaction topologies can be controlled through a judicious choice of the
      phosphine catalyst and the structural variations of starting materials. This
      Tutorial Review presents selected examples of nucleophilic phosphine catalysis
      using allenes and electrophiles. 

PMID- 24663291
TI  - A BLIND COMPRESSIVE SENSING FRAMEWORK FOR ACCELERATED DYNAMIC MRI.
AB  - We propose a novel blind compressive sensing (BCS) frame work to recover dynamic
      images from under-sampled measurements. This scheme models the the dynamic signal
      as a sparse linear combination of temporal basis functions, chosen from a large
      dictionary. The dictionary and the sparse coefficients are simultaneously
      estimated from the under-sampled measurements. Since the number of degrees of
      freedom of this model is much smaller than that of current low-rank methods, this
      scheme is expected to provide improved reconstructions for datasets with
      considerable inter-frame motion. We develop an efficient majorize-minimize
      algorithm to solve for the dynamic images. We use a continuation strategy to
      minimize the convergence of the algorithm to local minima. Numerical comparisons
      of the BCS scheme with low-rank methods demonstrate the significant improvement
      in performance in the presence of motion.

PMID- 24663292
TI  - Template-free synthesis of functional 3D BN architecture for removal of dyes from
      water.
AB  - Three-dimensional (3D) architectures are of interest in applications in
      electronics, catalysis devices, sensors and adsorption materials. However, it is
      still a challenge to fabricate 3D BN architectures by a simple method. Here, we
      report the direct synthesis of 3D BN architectures by a simple thermal treatment
      process. A 3D BN architecture consists of an interconnected flexible network of
      nanosheets. The typical nitrogen adsorption/desorption results demonstrate that
      the specific surface area for the as-prepared samples is up to 1156 m(2) g(-1),
      and the total pore volume is about 1.17 cm(3) g(-1). The 3D BN architecture
      displays very high adsorption rates and large capacities for organic dyes in
      water without any other additives due to its low densities, high resistance to
      oxidation, good chemical inertness and high surface area. Importantly, 88% of the
      starting adsorption capacity is maintained after 15 cycles. These results
      indicate that the 3D BN architecture is potential environmental materials for
      water purification and treatment.

PMID- 24663293
TI  - Transetherification on polyols by intra- and intermolecular nucleophilic
      substitutions.
AB  - Transetherification on polyols involving intra- and intermolecular nucleophilic
      substitutions is reported. Di- or trialkoxide formation of propane-1,3-diol or 2
      (hydroxymethyl)propane-1,3-diol derivatives by NaH triggers the reaction via
      oxetanes formation, where the order to add NaH and a polyol significantly
      influences the yields of products. It was demonstrated that the protective group
      on the pentaerythritol skeleton is apparently transferred to the hydrophilic and
      hydrophobic chain molecules bearing a leaving group in one-step, and a protective
      group conversion from tosyl to benzyl was successful using a benzyl-appending
      triol to afford a desired product in 67% yield. 

PMID- 24663296
TI  - Generalized numerical pressure distribution model for smoothing polishing of
      irregular midspatial frequency errors.
AB  - The smoothing effect of the rigid lap plays an important role in controlling
      midspatial frequency errors (MSFRs). At present, the pressure distribution
      between the polishing pad and processed surface is mainly calculated by Mehta's
      bridging model. However, this classic model does not work for the irregular MSFR.
      In this paper, a generalized numerical model based on the finite element method
      (FEM) is proposed to solve this problem. First, the smoothing polishing (SP)
      process is transformed to a 3D elastic structural FEM model, and the governing
      matrix equation is gained. By virtue of the boundary conditions applied to the
      governing matrix equation, the nodal displacement vector and nodal force vector
      of the pad can be attained, from which the pressure distribution can be
      extracted. In the partial contact condition, the iterative method is needed. The
      algorithmic routine is shown, and the applicability of the generalized numerical
      model is discussed. The detailed simulation is given when the lap is in contact
      with the irregular surface of different morphologies. A well-designed SP
      experiment is conducted in our lab to verify the model. A small difference
      between the experimental data and simulated result shows that the model is
      totally practicable. The generalized numerical model is applied on a Phi500  mm
      parabolic surface. The calculated result and measured data after the SP process
      have been compared, which indicates that the model established in this paper is
      an effective method to predict the SP process.

PMID- 24663295
TI  - Indication for the use of an interposed graft during portal vein and/or superior
      mesenteric vein reconstruction in pancreatic resection based on perioperative
      outcomes.
AB  - PURPOSE: Combined portal vein and/or superior mesenteric vein (PV/SMV) resection
      with pancreatic resection sometimes leads to prolonged survival for patients with
      pancreatic cancer. In this study, we evaluated perioperative outcomes of patients
      with PV/SMV reconstruction and considered indications for the use of a graft
      during this procedure. METHODS: We performed PV/SMV resection with pancreatic
      resection in 128 patients, including 14 using grafts. Complications associated
      with PV/SMV reconstruction and harvesting venous grafts and reconstructed PV/SMV
      patency during follow-up were assessed. RESULTS: Of the 128 patients, 5 underwent
      total pancreatectomy, 99 pancreaticoduodenectomy, and 24 distal pancreatectomy.
      In the 14 patients who underwent PV/SMV reconstruction with grafts, the grafts
      were harvested from the external iliac vein (EIV) in 10 patients and internal
      jugular vein (IJV) in the other 4. Five patients (3.9 %) had an intraoperative or
      postoperative acute thrombus or stenosis of reconstructed PV/SMV after direct end
      to-end anastomosis. However, PV/SMV patency was excellent after reconstruction
      using grafts. There were no significant differences in other complications
      between groups with and without the use of grafts. Three patients (30 %) with EIV
      grafts had postoperative leg edema, and one of them required analgesics until his
      death because of leg pain caused by compartment syndrome, whereas no patients
      with IJV grafts had complications associated with sacrificing veins. CONCLUSIONS:
      Depending on the length and/or position of the removed PV/SMV segment, interposed
      graft may be required for reconstruction in some patients, and the use of graft
      vein, particularly using IJV, is an appropriate procedure that is not associated
      with any complications.

PMID- 24663297
TI  - Trench-embedding fiber taper sensor fabricated by a femtosecond laser for gas
      refractive index sensing.
AB  - A fiber in-line, multimode coupling interferometer with a trench-embedding, fiber
      taper probe is proposed and fabricated by femtosecond-laser-induced water
      breakdown. The reflection-type taper probe is used for gas refractive index (RI)
      detection from 1.0001143 to 1.0002187 and temperature sensing from 50 degrees C
      to 500 degrees C. The largest RI sensitivity of the taper probe embedded with a
      trench at a width of 18.4 MUm is 669.502  nm/RIU for hybrid nitrogen and helium.
      Temperature sensitivity is 9.97  pm/ degrees C and it shows good linearity
      through the whole testing range. The new-type multimode interferometer is
      appropriate for high-accuracy gas RI detection of micrometer-scale spaces and
      wide-range temperature compensation can be realized. 

PMID- 24663298
TI  - Terahertz time-domain imaging of hidden defects in wooden artworks: application
      to a Russian icon painting.
AB  - We use terahertz time-domain imaging and time-of-flight tomography to examine
      subsurface defects in an early-19th-century Russian icon painting. In the
      transmission geometry, we distinguish between native wood and higher-absorption
      knotted wood. In reflection, we identify a void in the wood filled with foreign
      filler material. By using time-of-flight tomographic analysis, we ascertain the
      depth of burial of the defects. This information helps us to identify the cause
      of surface faults in the painting, thus allowing the conservators to choose an
      adequate restoration strategy. 

PMID- 24663299
TI  - Stabilization system for holographic recording of volume Bragg gratings using a
      corner cube retroreflector.
AB  - Volume Bragg gratings serve an important role in laser development as devices
      that are able to manipulate both the wavelength and angular spectrum of light. A
      common method for producing gratings is holographic recording of a two collimated
      beam interference pattern in a photosensitive material. This process requires
      stability of the recording system at a level of a fraction of the recording
      wavelength. A new method for measuring and stabilizing the phase of the recording
      beams is presented that is extremely flexible and simple to integrate into an
      existing holographic recording setup and independent of the type of recording
      media. It is shown that the presented method increases visibility of an
      interference pattern and for photo-thermo-refractive glass enables enhancement of
      the spatial refractive index modulation. The use of this technique allows for
      longer recording times that can lead to the use of expanded recording beams for
      large aperture gratings. 

PMID- 24663300
TI  - Low-coherence heterodyne interferometry using an achromatic frequency shifter
      based on a frequency-domain optical delay line.
AB  - In this paper a high-sensitivity low-coherence heterodyne interferometric system
      consisting of two polarizing Michelson interferometers arranged in tandem is
      presented. A compact frequency-domain optical delay line was placed in the first
      interferometer to produce a 4.4 kHz frequency shift for broadband near-infrared
      light. The frequency shift was wavelength independent because the scanning delay
      line had a zero-group-delay configuration. The fringe amplitude and phase of a
      low-coherence interference signal were detected using a lock-in amplifier. The
      experimental results show that the signal-to-noise ratio in the proposed
      technique is more than 30-fold higher than that of conventional low-coherence
      homodyne interferometry. 

PMID- 24663301
TI  - Comparison of a new photosensitizer with erythrosine B in an AA/PVA-based
      photopolymer material.
AB  - Dyes often act as the photoinitiator PI/photosensitizer PS in photopolymer
      materials and are therefore of significant interest. The properties of the PI/PS
      used strongly influences grating formation when the material layer is exposed
      holographically. In this paper, the ability of a recently synthesized dye, D_1,
      to sensitize an acrylamide/polyvinyl alcohol (AA/PVA) based photopolymer is
      examined, and the material performance is characterized using an extended
      nonlocal photopolymerization-driven diffusion model. Electron spin resonance spin
      trapping (ESR-ST) experiments are also carried out to characterize the generation
      of the initiator/primary radical, R(*), during exposure. The results obtained are
      then compared with those for the corresponding situation when using a xanthene
      dye, i.e., erythrosine B, under the same experiment conditions. The results
      indicate that the nonlocal effect is greater when this new photosensitizer is
      used in the material. Analysis indicates that this is the case because of the
      dye's (D_1) weak absorptivity and the resulting slow rate of primary radical
      production.

PMID- 24663302
TI  - Sellmeier and thermo-optic dispersion formulas for LiInSe2.
AB  - This paper reports on the improved Sellmeier and thermo-optic dispersion formulas
      for LiInSe2, which provide a good reproduction of the temperature-dependent phase
      matching conditions for the nonlinear frequency-conversion experiments achieved
      in the 1.0642-10.5910 MUm range.

PMID- 24663303
TI  - Optically significant particle sizes in seawater.
AB  - Small particles (<10  MUm) are often considered to play the dominant role in
      controlling scattering and absorption due to their relatively large numbers,
      which are typically found in the ocean. Here we present an approach for
      quantifying the size range of particles that contribute significantly to bulk
      inherent optical properties. We present a numerical assessment of the variability
      in optically significant particle sizes for simplistic populations that conform
      to the assumptions of homogeneous, spherical particles, and power-law size
      distributions. We use numerical predictions from Mie theory to suggest minimum
      and maximum particle sizes required for accurate predictions and observations of
      ocean optics for different particle size distributions (PSDs). When considering
      observed ranges of PSDs, our predictions suggest the need for measurements of
      optical properties and particles to capture information from particle sizes
      between diameters of 0.05-2000 MUm in order to properly constrain relationships
      between particles and their associated optical properties. Natural particle
      populations in the ocean may present more complex PSDs that could be analyzed
      using the method presented here to establish optically significant size classes.

PMID- 24663304
TI  - Optimum values of air-filling fraction for photonic crystal fibers with different
      configurations and fixed number of air rings.
AB  - In this study, a Gaussian amp function related to the Gaussian family is employed
      to approximate the output intensity profile of various arrangements of air holes
      in photonic crystal fibers (PCFs) with a fixed number of air rings (N=4). It is
      shown that d/Lambda=0.5 can be the best minimum value of air-filling fraction for
      all of the studied PCFs when lambda=1.35  MUm, whereas, for lambda=1.55 and 1.65
      MUm, d/Lambda=0.6 is suitable for achieving the maximum output intensity with
      very low confinement loss.

PMID- 24663305
TI  - Design, fabrication, and characterization of thermoplastic microlenses for fiber
      optic probe imaging.
AB  - Microlens-ended fibers could find great usefulness in future biomedical
      applications, particularly in endoscopic imaging applications. In this context,
      this paper focuses on microlens-attached specialty optical fibers such as imaging
      fiber that can be used for probe imaging applications. Stand-alone self-aligned
      polymer microlenses have been fabricated by microcompression molding. The
      fabrication parameters have been optimized for different materials, such as
      poly(methyl methacrylate) (PMMA), polycarbonate (PC Lexan 123R), Zeonor 1060R
      (ZNR), and Topas COC. A comparison study of the focusing and spatial resolution
      of the fabricated lenses is performed prior to employing them for fiber-optic
      fluorescence imaging applications. 

PMID- 24663306
TI  - Argon mini-arc meets its match: use of a laser-driven plasma source in
      ultraviolet-detector calibrations.
AB  - The National Institute of Standards and Technology operates two spectral
      comparator facilities, both of which are used to provide detector calibrations
      from the ultraviolet to the near-infrared spectral range. One, the Ultraviolet
      Spectral Comparator Facility (UV SCF), has been in operation for more than two
      decades, providing one of the core calibration services. Recently, the
      illumination source used in the UV SCF has been changed from an argon mini-arc
      source to a laser-driven plasma light source. This new source has higher
      brightness, a smaller source size, better temporal stability, and much better
      conversion efficiency than the previous source. The improvements in the
      capabilities are summarized. 

PMID- 24663307
TI  - Micro-Spec: an ultracompact, high-sensitivity spectrometer for far-infrared and
      submillimeter astronomy.
AB  - High-performance, integrated spectrometers operating in the far-infrared and
      submillimeter ranges promise to be powerful tools for the exploration of the
      epochs of reionization and initial galaxy formation. These devices, using high
      efficiency superconducting transmission lines, can achieve the performance of a
      meter-scale grating spectrometer in an instrument implemented on a 4 inch silicon
      wafer. Such a device, when combined with a cryogenic telescope in space, provides
      an enabling capability for studies of the early universe. Here, the optical
      design process for Micro-Spec (MU-Spec) is presented, with particular attention
      given to its two-dimensional diffractive region, where the light of different
      wavelengths is focused on the different detectors. The method is based on the
      stigmatization and minimization of the light path function in this bounded
      region, which results in an optimized geometrical configuration. A point design
      with an efficiency of ~90% has been developed for initial demonstration and can
      serve as the basis for future instruments. Design variations on this
      implementation are also discussed, which can lead to lower efficiencies due to
      diffractive losses in the multimode region.

PMID- 24663308
TI  - Passivation process in quasi-continuous laser derusting with intermediate pulse
      width and line-scanning method.
AB  - Floating rust composed of particles and aggregates is the primary product of iron
      or steel corrosion. Because the floating rust has a porous structure and small
      thickness, part of the irradiating laser energy can be transmitted through the
      rust layer and be absorbed by the iron substrate. The adherent force between the
      floating rust and the metal substrate is weak. In this paper we carried out a
      series of experiments on this specific rust type to achieve laser derusting and
      passivating simultaneously. We used a line-scanning method (50% overlapping ratio
      between adjacent laser spots) to get the nearly average uniform distribution of
      laser fluence in a large cleaning area. The laser irradiation can directly heat a
      metal surface to cause thermo-elastic vibration to shake off the rust layer and
      to cause oxidization to form a protective layer. The most important factor of
      laser passivating is that the iron surface must be heated to the melting point of
      iron but not much higher. During this short melting period, on the one hand the
      iron surface could be oxidized completely; on the other hand the melting of the
      iron surface could make uniform the oxygen concentration and temperature in the
      molten iron bath. 

PMID- 24663309
TI  - Analytic solution of cut-off wavelength of bend-insensitive fibers based on
      frustrated total reflection.
AB  - An analytic method for solving the cut-off wavelength of single groove-assisted
      bend-insensitive fiber (BIF) was proposed. Combined with the concepts of
      frustrated total reflection and numerical aperture, the cut-off wavelength
      formula for the BIF was deduced. Experimental results showed that, compared to
      the traditional analytic and numeric methods, this method had higher accuracy in
      the calculation of cut-off wavelength for BIFs that had a large proportion of
      depressed inner-cladding layer, which significantly expanded the range of
      accurately predicting the cut-off wavelength. 

PMID- 24663310
TI  - Terahertz spoof plasmonic coaxial microcavity.
AB  - We theoretically demonstrate a subwavelength spoof surface-plasmon-polariton
      (SPP) microcavity on a planar metallic surface working at the terahertz regime
      with a high-quality factor and ultra-small mode volume. The microcavity is based
      on plasmonic and metamaterial notions, and it consists of an easy-to-manufacture
      circular aperture and a bell-shaped metallic core. It is shown that such a
      structure can sustain SPP eigenmodes whose fields are tightly trapped within the
      microcavity. Using the proposed structure, a total Q factor of 1000 (including
      losses from metals at low temperatures) and subwavelength mode volume of
      0.00018(lambda/2)3 can be achieved in the THz range for the fundamental surface
      plasmonic eigenmode at room temperature. Moreover, the key figures of merit such
      as resonance frequency can be flexibly tuned by modifying the geometry of the
      microcavity, making it attractive for broad applications in filters, light
      sources, energy storage, and on-chip optical communications.

PMID- 24663311
TI  - Speed, optical power, and off-axis imaging improvement of refractive liquid
      crystal lenses.
AB  - Two design approaches (multicell and addition of phase resets in single cell) are
      introduced to optimize the performances of tunable refractive liquid crystal
      lenses, including improvements on the switching speed, optical power, and the off
      axis, wide-angle imaging performance. Key parameters and advantages for each
      method are discussed, and their effects on the performance are demonstrated in
      detail with numerical calculations. 

PMID- 24663312
TI  - Background modeling for moving object detection in long-distance imaging through
      turbulent medium.
AB  - A basic step in automatic moving objects detection is often modeling the
      background (i.e., the scene excluding the moving objects). The background model
      describes the temporal intensity distribution expected at different image
      locations. Long-distance imaging through atmospheric turbulent medium is affected
      mainly by blur and spatiotemporal movements in the image, which have
      contradicting effects on the temporal intensity distribution, mainly at edge
      locations. This paper addresses this modeling problem theoretically, and
      experimentally, for various long-distance imaging conditions. Results show that a
      unimodal distribution is usually a more appropriate model. However, if image
      deblurring is performed, a multimodal modeling might be more appropriate. 

PMID- 24663314
TI  - Scatterometry specialized for a highly asymmetric triangular grating on a
      transparent substrate.
AB  - We present a specialized scatterometry method to measure the groove profiles of
      highly asymmetric triangular gratings. Compared with the conventional
      scatterometry working in a specular way, this method utilizes diffraction spectra
      of the reflected +/-1st orders and is good at measuring this kind of asymmetric
      grating with a higher sensitivity. In our work, diffraction efficiency angular
      spectra at a single wavelength are measured and passed on to a parameter
      optimization process to retrieve three profile defining parameters. Final results
      are compared with the ones from an atomic force microscope and discrepancies are
      discussed and explained. 

PMID- 24663315
TI  - Design of off-axis arranged light-emitting diodes and dual dichroic mirrors based
      color mixing system for micro-projection display.
AB  - A simple but efficient color mixing system for micro-projection display is
      presented in this paper, which has employed off-axis arranged LEDs and
      specifically designed dichroic mirrors in order to achieve higher optical
      efficiency and a better space utilization ratio compared with previous systems.
      The design method of the dual-dichroic-mirror (DDM) system is investigated both
      analytically and numerically. The design results are consistent with the
      theoretical calculation, and the advantages of the proposed DDM system are
      obvious. Compared with traditional systems that are commonly used in micro
      projectors, the DDM system has indicated a much higher collection efficiency (up
      to 93.36%) with a significantly reduced size of 1.47 cc. Equipped with the DDM
      system, the designed micro-projector has realized an energy utilization ratio of
      76.92% and an irradiance uniformity of 96.59% with an ultra-compact volume of
      28.8  mm*28.1  mm*10  mm, which is competent for embedded projection display. It
      is believed that such a design has good prospects in commercialized production in
      the future.

PMID- 24663316
TI  - Three-dimensional multi-walled carbon nanotube arrays coated by gold-sol as a
      surface-enhanced Raman scattering substrate.
AB  - We demonstrated a three-dimensional (3D) surface-enhanced Raman scattering (SERS)
      substrate consisting of large area carbon nanotube (CNT) arrays coated by gold
      sol nanoparticles. A low-cost, simple process is used to prepare Au-decorated 3D
      CNT arrays. The SERS enhancement from the 3D CNT arrays, and two-dimensional (2D)
      CNT films substrates coated by different size gold-sol nanoparticles, was
      experimentally verified with Rhodamine 6G as the probe analyte. The experiments
      showed that the 3D CNT arrays substrate has a higher Raman enhancement compared
      with 2D CNT arrays substrate and planar glass substrate, due to the large
      specific surface area of CNT arrays and more gold nanoparticles on the CNT arrays
      sidewalls, which contribute the electromagnetic field and Raman intensity.
      Meanwhile, the 3D structure could enhance the excitation light trapping in CNT
      arrays, consequently increasing the light interaction with Au nanoparticles. 

PMID- 24663317
TI  - Development of an artificial compound eye system for three-dimensional object
      detection.
AB  - A compound eye has the advantages of a large field of view, high sensitivity, and
      compact structure, showing that it can be applicable for 3D object detection. In
      this work, an artificial compound eye system is developed for 3D object
      detection, consisting of a layer of lenslets and a prism-like beam-steering lens.
      A calibration method is developed for this system, with which the correspondences
      between incident light rays and the relevant image points can be obtained
      precisely using an active calibration pattern at multiple positions.
      Theoretically, calibration patterns at two positions are sufficient for system
      calibration, although more positions will increase the accuracy of the result. 3D
      positions of point objects are calculated to evaluate the system, which are
      obtained by the intersection of multiple incident light rays in the least-squares
      sense. Experimental results show that the system can detect an object with
      angular accuracy of better than 1 mrad, demonstrating the feasibility of the
      proposed compound eye system. With a 2D scanning device, the system can be
      extended for general object detection in 3D space.

PMID- 24663318
TI  - Composite chromium and graphene oxide as saturable absorber in ytterbium-doped Q
      switched fiber lasers.
AB  - In recent years, graphene and its compounds (e.g., oxides) have been used as
      saturable absorbers in passive Q-switched and mode-locked lasers, leading to the
      fabrication of compact pulsed fiber lasers. In this article, we study the
      operation of a Q-switched ytterbium-doped fiber ring laser based on a composite
      saturable absorber made of graphene oxide and chromium. We show that the addition
      of a thin layer of chromium can lead to pulse durations ranging from 3.5 to 9.4
      MUs and subsequently increasing the laser peak power.

PMID- 24663319
TI  - Detecting and tracking moving objects in long-distance imaging through turbulent
      medium.
AB  - The challenge of detecting and tracking moving objects in imaging throughout the
      atmosphere stems from the atmospheric turbulence effects that cause time-varying
      image shifts and blur. These phenomena significantly increase the miss and false
      detection rates in long-range horizontal imaging. An efficient method was
      developed, which is based on novel criteria for objects' spatio-temporal
      properties, to discriminate true from false detections, following an adaptive
      thresholding procedure for foreground detection and an activity-based false alarm
      likeliness masking. The method is demonstrated on significantly distorted videos
      and compared with state of the art methods, and shows better false alarm and miss
      detection rates. 

PMID- 24663320
TI  - Hartmann tests to measure the spherical and cylindrical curvatures and the axis
      orientation of astigmatic lenses or optical surfaces.
AB  - The measurement of astigmatic lenses, optical surfaces or wavefronts are a highly
      studied problem and many different instruments have been commercially fabricated
      to perform this task. Many of them use a Hartmann arrangement to obtain the
      result. In this paper, we analyze with detail the algorithms that can be used to
      make the necessary calculations and propose several alternatives with different
      advantages and disadvantages. Different mathematical algorithms that are involved
      in the calculation process have been given whereas any description of the
      instrument itself is not proposed, but only the different mathematical algorithms
      that are involved in the calculation process. 

PMID- 24663321
TI  - Experimental verification of the modified spring-mass theory of fiber Bragg
      grating accelerometers using transverse forces.
AB  - A fiber Bragg grating (FBG) accelerometer using transverse forces is more
      sensitive than one using axial forces with the same mass of the inertial object,
      because a barely stretched FBG fixed at its two ends is much more sensitive to
      transverse forces than axial ones. The spring-mass theory, with the assumption
      that the axial force changes little during the vibration, cannot accurately
      predict its sensitivity and resonant frequency in the gravitational direction
      because the assumption does not hold due to the fact that the FBG is barely
      prestretched. It was modified but still required experimental verification due to
      the limitations in the original experiments, such as the (1) friction between the
      inertial object and shell; (2) errors involved in estimating the time-domain
      records; (3) limited data; and (4) large interval ~5  Hz between the tested
      frequencies in the frequency-response experiments. The experiments presented here
      have verified the modified theory by overcoming those limitations. On the
      frequency responses, it is observed that the optimal condition for simultaneously
      achieving high sensitivity and resonant frequency is at the infinitesimal
      prestretch. On the sensitivity at the same frequency, the experimental
      sensitivities of the FBG accelerometer with a 5.71 gram inertial object at 6 Hz
      (1.29, 1.19, 0.88, 0.64, and 0.31  nm/g at the 0.03, 0.69, 1.41, 1.93, and 3.16
      nm prestretches, respectively) agree with the static sensitivities predicted
      (1.25, 1.14, 0.83, 0.61, and 0.29  nm/g, correspondingly). On the resonant
      frequency, (1) its assumption that the resonant frequencies in the forced and
      free vibrations are similar is experimentally verified; (2) its dependence on the
      distance between the FBG's fixed ends is examined, showing it to be independent;
      (3) the predictions of the spring-mass theory and modified theory are compared
      with the experimental results, showing that the modified theory predicts more
      accurately. The modified theory can be used more confidently in guiding its
      design by predicting its static sensitivity and resonant frequency, and may have
      applications in other fields for the scenario where the spring-mass theory fails.

PMID- 24663322
TI  - Influence of finite-sized detection solid angle on bidirectional reflectance
      distribution function measurements.
AB  - This paper deals with limitations and often overlooked sources of error
      introduced in compact double-beam goniophotometers. It is shown that relative
      errors in measured radiance factor, comparable to the total measurement
      uncertainty, can be introduced if recommended corrections are not carried out.
      Two different error sources are investigated, both related to the size of the
      detection solid angle. The first is a geometrical error that occurs when the size
      of the illuminated area and detector aperture are comparable to the distance
      between them. The second is a convolution error due to variations in radiant flux
      over the detector aperture, which is quantified by simulating the full 3D
      bidirectional reflectance distribution function (BRDF) of a set of samples with
      different degrees of anisotropic reflectance. The evaluation is performed for a
      compact double-beam goniophotometer using different detection solid angles, and
      it is shown that both error sources introduce relative errors of 1%-3%, depending
      on viewing angle and optical properties of the sample. Commercially available
      compact goniophotometers, capable of absolute measurements, are becoming more and
      more common, and the findings in this paper are therefore important for anyone
      using or planning to use this type of instrument. 

PMID- 24663323
TI  - Chemical mechanical polishing to improve the efficiency uniformity of beam
      sampling grating.
AB  - In order to improve the efficiency uniformity of large-aperture beam sampling
      gratings (BSGs), a conventional chemical mechanical polishing (CMP) process of
      fused silica by CeO2 slurry is proposed to modify their groove profiles. With the
      proposed CMP process, the efficiency uniformity of several BSGs with an aperture
      of 430  mm*430  mm has been successfully controlled within an rms of 5%. The
      proposed CMP process is an effective method to improve the efficiency uniformity
      of large-aperture BSGs. Using the proposed CMP process, the requirement of the
      uniformity of the holographic ion beam etching process can be released in the
      realization of large-aperture BSGs.

PMID- 24663324
TI  - Analysis of the effects of applying external fields and device dimensions
      alterations on GaAs/AlGaAs multiple quantum well slow light devices based on
      excitonic population oscillation.
AB  - This paper demonstrates the effects of applying magnetic and electric fields and
      physical dimensions alterations on AlGaAs/GaAs multiple quantum well (QW) slow
      light devices. Physical parameters include quantum well sizes and number of
      quantum wells. To the best of our knowledge, this is the first analysis of the
      effects of both applying magnetic/electric fields and physical parameters
      alterations and the first suggestion for matching the prefabrication and post
      fabrication tuning of the slow light devices based on excitonic population
      oscillations. The aim of our theoretical analysis is controlling the optical
      properties such as central frequency, bandwidth, and slow down factor (SDF) in
      slow light devices based on excitonic population oscillation to achieve better
      tuning. To reach these purposes, first we investigate the quantum well size and
      number of quantum wells alteration effects. Next, we analyze the effects of
      applying magnetic and electric fields to the multiple quantum well structure,
      separately. Finally, physical parameters and applied external fields are changed
      for measuring frequency shift and SDF for coherent population oscillation slow
      light devices. The results show the available central frequency shifts in about
      1.6 THz at best. Also the SDF value improvement is about one order of magnitude.
      These results will be applicable for optical nonlinearity enhancements, all
      optical signal processing, optical communications, all-optical switches, optical
      modulators, and variable true delays.

PMID- 24663325
TI  - Simulation of an asymmetric contacted carbon nanotube for solar-energy
      harvesting.
AB  - Nanostructured materials offer great prospects in helping solar-energy harvesting
      devices to achieve their envisioned performances. Carbon nanotubes (CNT)-based
      devices were among the first to be proposed for this task. These devices are
      based on CNT field-effect transistors and CNT diodes. In this paper, the
      photovoltaic behavior of a diode structure formed from an asymmetrically
      contacted intrinsic CNT with scandium and palladium electrodes as source and
      drain, respectively, is investigated. A semi-classical simulator, which combines
      a quantum solution, for transmission through the electrodes/CNT interfaces with
      the semi-classical drift-diffusion equation and continuity equation for charge
      transport in the CNT has been built. The obtained simulation outcomes are
      compared with the available published experimental results. 

PMID- 24663326
TI  - Thermal tuning of volume Bragg gratings for spectral beam combining of high-power
      fiber lasers.
AB  - High-radiance lasers are desired for many applications in defense and
      manufacturing. Spectral beam combining (SBC) by volume Bragg gratings (VBGs) is a
      very promising method for high-radiance lasers that need to achieve 100 kW level
      power. Laser-induced heating of VBGs under high-power radiation presents a
      challenge for maintaining Bragg resonance at various power levels without
      mechanical realignment. A novel thermal tuning technique and apparatus is
      presented that enables maintaining peak efficiency operation of the SBC system at
      various power levels without any mechanical adjustment. The method is
      demonstrated by combining two high-power ytterbium fiber lasers with high
      efficiency from low power to full combined power of 300 W (1.5 kW effective
      power), while maintaining peak combining efficiency within 0.5%.

PMID- 24663327
TI  - Diabetes and risk of tuberculosis relapse: nationwide nested case-control study.
AB  - The aim of this study was to investigate the association between diabetes
      mellitus (DM) and tuberculosis (TB) relapse using the nationwide TB registry in
      Taiwan. We conducted a case-control study nested within a nationwide cohort of
      all incident cases of pulmonary TB that were notified during 2006-2007 and had
      completed anti-TB treatment. The relapse of TB was confirmed by bacteriological
      or pathological findings. For each relapse case, one control was selected from
      the study cohort matching by time since treatment completion. DM status was
      ascertained by medical chart review and cross-matching with the National Health
      Insurance claims database. A total of 305 cases of relapse were identified after
      a median follow-up of 3 years (relapse rate: 488 per 100,000 person-year; 95%
      confidence interval (CI): 434-546). Presence of DM during previous anti-TB
      treatment was 34.0% and 22.7% in cases and controls, respectively. After
      adjusting for other potential confounders, DM was associated with increased risk
      of TB relapse (adjusted odds ratio: 1.96, 95% CI: 1.22-3.15). Only one-third of
      the DM-TB patients in our study received glycaemic monitoring using HbA1c during
      anti-TB treatment. Presence of DM was independently associated with risk of TB
      relapse. TB programs should seriously consider rigorous glucose control in DM-TB
      patients. 

PMID- 24663328
TI  - Convallatoxin, a dual inducer of autophagy and apoptosis, inhibits angiogenesis
      in vitro and in vivo.
AB  - Autophagy and apoptosis are important processes that control cellular homeostasis
      and have been highlighted as promising targets for novel cancer therapies. Here,
      we identified convallatoxin (CNT), isolated from Antiaris toxicaria, as a dual
      inducer of autophagy and apoptosis. CNT exerts cytotoxic effects on a number of
      cancer and normal cell lines and induces apoptosis by increasing caspase-3 and
      poly ADP ribose polymerase (PARP) cleavage. Moreover, dose- and time-dependent
      autophagic activity was detected in CNT-treated cells, and mammalian target of
      rapamycin (mTOR)/p70S6K signal pathway inhibition was observed. Notably, CNT
      inhibits human umbilical vein endothelial cell (HUVEC) growth and exerts anti
      angiogenic activity in vitro and in vivo. Collectively, these results demonstrate
      that the naturally occurring compound, CNT, is a novel anti-angiogenic compound
      via dual inducing of autophagy and apoptosis. 

PMID- 24663329
TI  - Epidemiological analysis, detection, and comparison of space-time patterns of
      Beijing hand-foot-mouth disease (2008-2012).
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) mostly affects the health of
      infants and preschool children. Many studies of HFMD in different regions have
      been published. However, the epidemiological characteristics and space-time
      patterns of individual-level HFMD cases in a major city such as Beijing are
      unknown. The objective of this study was to investigate epidemiological features
      and identify high relative risk space-time HFMD clusters at a fine spatial scale.
      METHODS: Detailed information on age, occupation, pathogen and gender was used to
      analyze the epidemiological features of HFMD epidemics. Data on individual-level
      HFMD cases were examined using Local Indicators of Spatial Association (LISA)
      analysis to identify the spatial autocorrelation of HFMD incidence. Spatial
      filtering combined with scan statistics methods were used to detect HFMD
      clusters. RESULTS: A total of 157,707 HFMD cases (60.25% were male, 39.75% were
      female) reported in Beijing from 2008 to 2012 included 1465 severe cases and 33
      fatal cases. The annual average incidence rate was 164.3 per 100,000 (ranged from
      104.2 in 2008 to 231.5 in 2010). Male incidence was higher than female incidence
      for the 0 to 14-year age group, and 93.88% were nursery children or lived at
      home. Areas at a higher relative risk were mainly located in the urban-rural
      transition zones (the percentage of the population at risk ranged from 33.89% in
      2011 to 39.58% in 2012) showing High-High positive spatial association for HFMD
      incidence. The most likely space-time cluster was located in the mid-east part of
      the Fangshan district, southwest of Beijing. CONCLUSIONS: The spatial-time
      patterns of Beijing HFMD (2008-2012) showed relatively steady. The population at
      risk were mainly distributed in the urban-rural transition zones. Epidemiological
      features of Beijing HFMD were generally consistent with the previous research.
      The findings generated computational insights useful for disease surveillance,
      risk assessment and early warning.

PMID- 24663330
TI  - Esterase LpEst1 from Lactobacillus plantarum: a novel and atypical member of the
      alphabeta hydrolase superfamily of enzymes.
AB  - The genome of the lactic acid bacterium Lactobacillus plantarum WCFS1 reveals the
      presence of a rich repertoire of esterases and lipases highlighting their
      important role in cellular metabolism. Among them is the carboxylesterase LpEst1
      a bacterial enzyme related to the mammalian hormone-sensitive lipase, which is
      known to play a central role in energy homeostasis. In this study, the crystal
      structure of LpEst1 has been determined at 2.05 A resolution; it exhibits an
      alphabeta-hydrolase fold, consisting of a central beta-sheet surrounded by alpha
      helices, endowed with novel topological features. The structure reveals a dimeric
      assembly not comparable with any other enzyme from the bacterial hormone
      sensitive lipase family, probably echoing the specific structural features of the
      participating subunits. Biophysical studies including analytical gel filtration
      and ultracentrifugation support the dimeric nature of LpEst1. Structural and
      mutational analyses of the substrate-binding pocket and active site together with
      biochemical studies provided insights for understanding the substrate profile of
      LpEst1 and suggested for the first time the conserved Asp173, which is adjacent
      to the nucleophile, as a key element in the stabilization of the loop where the
      oxyanion hole resides. 

PMID- 24663331
TI  - Clinical questions raised by clinicians at the point of care: a systematic
      review.
AB  - IMPORTANCE: In making decisions about patient care, clinicians raise questions
      and are unable to pursue or find answers to most of them. Unanswered questions
      may lead to suboptimal patient care decisions. OBJECTIVE: To systematically
      review studies that examined the questions clinicians raise in the context of
      patient care decision making. DATA SOURCES: MEDLINE (from 1966), CINAHL (from
      1982), and Scopus (from 1947), all through May 26, 2011. STUDY SELECTION Studies
      that examined questions raised and observed by clinicians (physicians, medical
      residents, physician assistants, nurse practitioners, nurses, dentists, and care
      managers) in the context of patient care were independently screened and
      abstracted by 2 investigators. Of 21,710 citations, 72 met the selection
      criteria. DATA EXTRACTION AND SYNTHESIS: Question frequency was estimated by
      pooling data from studies with similar methods. MAIN OUTCOMES AND MEASURES:
      Frequency of questions raised, pursued, and answered and questions by type
      according to a taxonomy of clinical questions. Thematic analysis of barriers to
      information seeking and the effects of information seeking on decision making.
      RESULTS In 11 studies, 7012 questions were elicited through short interviews with
      clinicians after each patient visit. The mean frequency of questions raised was
      0.57 (95% CI, 0.38-0.77) per patient seen, and clinicians pursued 51% (36%-66%)
      of questions and found answers to 78% (67%-88%) of those they pursued. Overall,
      34% of questions concerned drug treatment, and 24% concerned potential causes of
      a symptom, physical finding, or diagnostic test finding. Clinicians' lack of time
      and doubt that a useful answer exists were the main barriers to information
      seeking. CONCLUSIONS AND RELEVANCE: Clinicians frequently raise questions about
      patient care in their practice. Although they are effective at finding answers to
      questions they pursue, roughly half of the questions are never pursued. This
      picture has been fairly stable over time despite the broad availability of online
      evidence resources that can answer these questions. Technology-based solutions
      should enable clinicians to track their questions and provide just-in-time access
      to high-quality evidence in the context of patient care decision making.
      Opportunities for improvement include the recent adoption of electronic health
      record systems and maintenance of certification requirements.

PMID- 24663332
TI  - Socioeconomic Position and Health-Seeking Behavior for Hearing Loss Among Older
      Adults in England.
AB  - OBJECTIVE: To examine whether socioeconomic position (SEP) is associated with
      progression in the health-seeking process for hearing loss. METHOD: Logistic
      regression of data from a cross-sectional survey representative of
      noninstitutionalized, 50 years and older population of England (ELSA wave 2,
      2004). Using self-reported hearing difficulty as starting point, we examined the
      association between SEP and health-seeking behaviors in 6 stages leading to
      hearing aid acquisition and use. RESULTS: Higher SEP was associated with lower
      odds of self-reported hearing difficulty, adjusted odds ratio [OR] = 0.87 (95%
      confidence interval [CI] 0.83-0.91, p < .001). There was marginal negative
      association between higher SEP and receiving hearing aid recommendation (adjusted
      OR = 0.88, 95% CI 0.78-0.99, p = .05). SEP was not associated with any other
      stage of health-seeking behavior. DISCUSSION: Among the noninstitutionalized
      older population of England, SEP-related inequalities exist in the prevalence of
      self-reported hearing loss. However, SEP is not strongly associated with
      progression in the remaining stages of health-seeking process during and after an
      individual's contact with the health system.

PMID- 24663333
TI  - Influence of copper nanoparticles on the physical-chemical properties of
      activated sludge.
AB  - The physical-chemical properties of activated sludge, such as flocculating
      ability, hydrophobicity, surface charge, settleability, dewaterability and
      bacteria extracellular polymer substances (EPS), play vital roles in the normal
      operation of wastewater treatment plants (WWTPs). The nanoparticles released from
      commercial products will enter WWTPs and can induce potential adverse effects on
      activated sludge. This paper focused on the effects of copper nanoparticles
      (CuNPs) on these specific physical-chemical properties of activated sludge. It
      was found that most of these properties were unaffected by the exposure to lower
      CuNPs concentration (5 ppm), but different observation were made at higher CuNPs
      concentrations (30 and 50 ppm). At the higher CuNPs concentrations, the sludge
      surface charge increased and the hydrophobicity decreased, which were attributed
      to more Cu2+ ions released from the CuNPs. The carbohydrate content of EPS was
      enhanced to defense the toxicity of CuNPs. The flocculating ability was found to
      be deteriorated due to the increased cell surface charge, the decreased
      hydrophobicity, and the damaged cell membrane. The worsened flocculating ability
      made the sludge flocs more dispersed, which further increased the toxicity of the
      CuNPs by increasing the availability of the CuNPs to the bacteria present in the
      sludge. Further investigation indicated that the phosphorus removal efficiency
      decreased at higher CuNPs concentrations, which was consistent with the
      deteriorated physical-chemical properties of activated sludge. It seems that the
      physical-chemical properties can be used as an indicator for determining CuNPs
      toxicity to the bacteria in activated sludge. This work is important because
      bacteria toxicity effects to the activated sludge caused by nanoparticles may
      lead to the deteriorated treatment efficiency of wastewater treatment, and it is
      therefore necessary to find an easy way to indicate this toxicity. 

PMID- 24663334
TI  - Cardiopulmonary fitness and heart rate recovery as predictors of mortality in a
      referral population.
AB  - BACKGROUND: Exercise testing provides valuable information in addition to ST
      segment changes. The present study evaluated the associations among exercise test
      parameters and all-cause mortality in a referral population. METHODS AND RESULTS:
      We examined conventional cardiovascular risk factors and exercise test parameters
      in 6546 individuals (mean age 49 years, 58% men) with no known cardiovascular
      disease who were referred to our clinic for exercise stress testing between 1993
      and 2003. The association of exercise parameters with mortality was assessed
      during a follow-up of 8.1+/-3.7 years. A total of 285 patients died during the
      follow-up period. Adjusting for age and sex, the variables associated with
      mortality were: smoking, diabetes, functional aerobic capacity (FAC), heart rate
      recovery (HRR), chronotropic incompetence, and angina during the exercise.
      Adjusting for cardiovascular risk factors (diabetes, smoking, body mass index,
      blood pressure, serum total, HDL, LDL cholesterol, and triglycerides) and other
      exercise variables in a multivariable model, the only exercise parameters
      independently associated with mortality were lower FAC (adjusted hazard ratio
      [HR] per 10% decrease in FAC, 1.21; 95% confidence interval [CI], 1.13 to 1.29;
      P<0.001), and abnormal HRR, defined as failure to decrease heart rate by 12 beats
      at 1 minute recovery (adjusted HR per 1-beat decrease, 1.05; 95% CI, 1.03 to
      1.07; P<0.001). The additive effects of FAC and HRR on mortality were also highly
      significant when considered as categorical variables. CONCLUSION: In this cohort
      of patients with no known cardiovascular disease who were referred for exercise
      electrocardiography, FAC and HRR were independently associated with all-cause
      mortality.

PMID- 24663335
TI  - Bedside tool for predicting the risk of postoperative atrial fibrillation after
      cardiac surgery: the POAF score.
AB  - BACKGROUND: Atrial fibrillation (AF) remains the most common complication after
      cardiac surgery. The present study aim was to derive an effective bedside tool to
      predict postoperative AF and its related complications. METHODS AND RESULTS: Data
      of 17 262 patients undergoing adult cardiac surgery were retrieved at 3 European
      university hospitals. A risk score for postoperative AF (POAF score) was derived
      and validated. In the overall series, 4561 patients (26.4%) developed
      postoperative AF. In the derivation cohort age, chronic obstructive pulmonary
      disease, emergency operation, preoperative intra-aortic balloon pump, left
      ventricular ejection fraction <30%, estimated glomerular filtration rate <15
      mL/min per m(2) or dialysis, and any heart valve surgery were independent AF
      predictors. POAF score was calculated by summing weighting points for each
      independent AF predictor. According to the prediction model, the incidences of
      postoperative AF in the derivation cohort were 0, 11.1%; 1, 20.1%; 2, 28.7%; and
      >=3, 40.9% (P<0.001), and in the validation cohort they were 0, 13.2%; 1, 19.5%;
      2, 29.9%; and >=3, 42.5% (P<0.001). Patients with a POAF score >=3, compared with
      those without arrhythmia, revealed an increased risk of hospital mortality (5.5%
      versus 3.2%, P=0.001), death after the first postoperative day (5.1% versus 2.6%,
      P<0.001), cerebrovascular accident (7.8% versus 4.2%, P<0.001), acute kidney
      injury (15.1% versus 7.1%, P<0.001), renal replacement therapy (3.8% versus 1.4%,
      P<0.001), and length of hospital stay (mean 13.2 versus 10.2 days, P<0.001).
      CONCLUSIONS: The POAF score is a simple, accurate bedside tool to predict
      postoperative AF and its related or accompanying complications.

PMID- 24663336
TI  - GWAS-identified common variants for obesity are not associated with the risk of
      developing colorectal cancer.
AB  - BACKGROUND: Observational studies have consistently associated obesity with
      colorectal cancer risk. Because both traits are genetically determined and share
      some metabolic biomarkers, we hypothesized that obesity-related polymorphisms
      could also influence the risk of developing colorectal cancer. METHODS: We
      conducted a comprehensive population-based case-control study in 1,792 German
      colorectal cancer cases and 1,805 controls to explore associations between 28
      obesogenic variants identified through genome-wide association studies (GWAS) and
      colorectal cancer risk. We also evaluated interactions between polymorphisms and
      body mass index (BMI), type II diabetes (T2D), and gender. RESULTS: No evidence
      of association between obesogenic variants and colorectal cancer risk was
      observed after correction for multiple testing. There was only a remarkable
      interaction between the LTArs1041981 polymorphism and gender, which modified the
      risk of colorectal cancer [Pinteraction = 0.002; males: odds ratio (OR), 1.14;
      95% confidence intervals (CI), 1.00-1.30 vs. females: OR, 0.83; 95% CI, 0.71
      0.97]. CONCLUSIONS: Our findings showed that obesogenic variants are not a major
      pathogenetic risk factor for colorectal cancer. IMPACT: This comprehensive
      population-based case-control study does not provide evidence of a shared genetic
      component between obesity and colorectal cancer.

PMID- 24663337
TI  - CXCL4-induced plaque macrophages can be specifically identified by co-expression
      of MMP7+S100A8+ in vitro and in vivo.
AB  - Macrophage heterogeneity in human atherosclerotic plaques has been recognized;
      however, markers for unequivocal identification of some subtypes are lacking. We
      found that the platelet chemokine CXCL4 induces a unique macrophage phenotype,
      which we proposed to call 'M4'. Here, we sought to identify suitable markers that
      identify M4 macrophages in vitro and in vivo. Using a stringent algorithm, we
      identified a set of potential markers from transcriptomic data derived from
      polarized macrophages. We specifically focused on matrix metalloproteinase (MMP)7
      and S100A8, the co-expression of which has not been described in any macrophage
      type thus far. We found dose- and time-dependent MMP7 and S100A8 expression in M4
      macrophages at the gene and protein levels. CXCL4-induced up-regulation of both
      MMP7 and S100A8 was curbed in the presence of heparin, which binds to CXCL4 and
      glycosaminoglycans, most likely representing the macrophage receptor for CXCL4.
      Immunofluorescence of post-mortem atherosclerotic coronary arteries identified
      CD68(+)MMP7(+), CD68(+)MMP7(-), CD68(+)S100A8(+) and CD68(+)S100A8(-)
      macrophages. A small proportion of MMP7(+)S100A8(+) macrophages most likely
      represent M4 macrophages. In summary, we have identified co-expression of MMP7
      and S100A8 to be a marker combination exclusively found in M4 macrophages. This
      finding may allow further dissection of the role of M4 macrophages in
      atherosclerosis and other pathologic conditions. 

PMID- 24663338
TI  - Time course of chemokine expression and leukocyte infiltration after acute
      skeletal muscle injury in mice.
AB  - Innate pro-inflammatory processes, such as chemokine signaling and leukocyte
      infiltration, predominate during the first 48 h after an acute skeletal muscle
      injury. However, the time course of chemokine expression and its relationship to
      leukocyte infiltration after acute muscle injury within this early post-injury
      time period has not been investigated. In this study, 46 anesthetized female
      C57BL/6NHsd mice underwent a closed crush injury of the gastrocnemius muscle and
      were euthanized 4, 8, 24 and 48 h post-injury. Microarray analysis found 14
      chemokine genes to be up-regulated during this period, 12 of which are involved
      in macrophage or neutrophil chemotaxis, with up-regulation peaking at either 8 or
      48 h. RT-PCR analysis on select chemokines confirmed the microarray activation
      pattern. Neutrophil infiltration patterns mirrored the time course of neutrophil
      related chemokines with Gr-1-, 1A8- and 7/4-positive neutrophils infiltrating the
      muscle 4 h after injury, decreasing at 48 h. Conversely, gene expression and
      relative quantification levels of macrophage-related chemokines Ccl2 and Ccl7
      peaked at 8 h, preceding the infiltration of CD68- and F4/80-positive
      macrophages, and protein expression of Ccl2 in the muscle. The up-regulation of
      other macrophage-related chemokines and their receptors peaked at 48 h post
      injury. 

PMID- 24663339
TI  - Cell counting in human endobronchial biopsies--disagreement of 2D versus 3D
      morphometry.
AB  - QUESTION: Inflammatory cell numbers are important endpoints in clinical studies
      relying on endobronchial biopsies. Assumption-based bidimensional (2D) counting
      methods are widely used, although theoretically design-based stereologic three
      dimensional (3D) methods alone offer an unbiased quantitative tool. We assessed
      the method agreement between 2D and 3D counting designs in practice when applied
      to identical samples in parallel. MATERIALS AND METHODS: Biopsies from segmental
      bronchi were collected from healthy non-smokers (n = 7) and smokers (n = 7),
      embedded and sectioned exhaustively. Systematic uniform random samples were
      immunohistochemically stained for macrophages (CD68) and T-lymphocytes (CD3),
      respectively. In identical fields of view, cell numbers per volume unit (NV) were
      assessed using the physical disector (3D), and profiles per area unit (NA) were
      counted (2D). For CD68+ cells, profiles with and without nucleus were separately
      recorded. In order to enable a direct comparison of the two methods, the zero
      dimensional CD68+/CD3+-ratio was calculated for each approach. Method agreement
      was tested by Bland-Altmann analysis. RESULTS: In both groups, mean CD68+/CD3+
      ratios for NV and NA were significantly different (non-smokers: 0.39 and 0.68,
      p<0.05; smokers: 0.49 and 1.68, p<0.05). When counting only nucleated CD68+
      profiles, mean ratios obtained by 2D and 3D counting were similar, but the
      regression-based Bland-Altmann analysis indicated a bias of the 2D ratios
      proportional to their magnitude. This magnitude dependent deviation differed
      between the two groups. CONCLUSIONS: 2D counts of cell and nuclear profiles
      introduce a variable size-dependent bias throughout the measurement range.
      Because the deviation between the 3D and 2D data was different in the two groups,
      it precludes establishing a 'universal conversion formula'.

PMID- 24663341
TI  - Socio-economic gradients in maternal and child health-seeking behaviours in
      egypt: systematic literature review and evidence synthesis.
AB  - BACKGROUND: Health-seeking behaviour lies on the direct pathway between socio
      economic position (SEP) and health outcomes. The objective of this systematic
      review is to identify and synthesise evidence of socio-economic gradients in
      health-seeking behaviours related to maternal and child health in Egypt. METHODS:
      Four databases (Medline, Embase, Global Health and Web of Science) were searched
      in September 2013 for material published in English from 1992 to 2013 for a
      combination of terms describing health-seeking behaviours, indicators of socio
      economic position and geographical limitation to Egypt. Findings of studies were
      described and synthesised in a narrative format as meta-analysis was not
      possible. FINDINGS: Among the 786 references identified, 10 articles met the
      inclusion criteria. Six studies examined maternal and five studies child health
      seeking behaviours (one study examined both). For maternal health, three
      dimensions of health-seeking behaviour (receipt of any care, type of care and
      intensity of care) were covered by studies of ante-natal and one dimension (type
      of care) by analyses of delivery care. For child health, two dimensions of
      preventive care (coverage of and intensity of immunisation) and three dimensions
      of curative care (receipt of any care, type and cost of care) were analysed.
      CONCLUSIONS: Based on two studies of time trends in nationally-representative
      surveys, socio-economic inequalities in seeking care for basic preventive and
      curative interventions in maternal and child health appear to have narrowed.
      Limited evidence of gradients in intensity of maternal preventive and provider
      selection in child curative care showed that inequalities may have widened. In
      studies of more geographically and socially homogeneous samples, fewer gradients
      were identified. Current body of evidence contains numerous limitations and gaps
      and is insufficient to draw a conclusive summary of such gradients. Improved
      understanding of SEP gradients is crucial in designing and prioritising
      interventions to equitably improve maternal and child health outcomes.

PMID- 24663342
TI  - Ubiquitin ligase EL5 maintains the viability of root meristems by influencing
      cytokinin-mediated nitrogen effects in rice.
AB  - Root formation is dependent on meristematic activity and is influenced by
      nitrogen supply. We have previously shown that ubiquitin ligase, EL5, in rice
      (Oryza sativa) is involved in the maintenance of root meristematic viability.
      When mutant EL5 protein is overexpressed to dominantly inhibit the endogenous EL5
      function in rice, primordial and meristematic necrosis ia observed. Here, we
      analysed the cause of root cell death in transgenic rice plants (mEL5)
      overexpressing EL5V162A, which encodes a partly inactive ubiquitin ligase. The
      mEL5 mutants showed increased sensitivity to nitrogen that was reflected in the
      inhibition of root formation. Treatment of mEL5 with nitrate or nitrite caused
      meristematic cell death accompanied by browning. Transcriptome profiling of whole
      roots exhibited overlaps between nitrite-responsive genes in non-transgenic (NT)
      rice plants and genes with altered basal expression levels in mEL5. Phytohormone
      profiling of whole roots revealed that nitrite treatment increased cytokinin
      levels, but mEL5 constitutively contained more cytokinin than NT plants and
      showed increased sensitivity to exogenous cytokinin. More superoxide was detected
      in mEL5 roots after treatment with nitrite or cytokinin, and treatment with an
      inhibitor of superoxide production prevented mEL5 roots from both nitrite- and
      cytokinin-induced meristematic cell death. These results indicate a nitrogen
      triggered pathway that leads to changes in root formation through the production
      of cytokinin and superoxide, on which EL5 acts to prevent meristematic cell
      death. 

PMID- 24663343
TI  - A survey of Populus PIN-FORMED family genes reveals their diversified expression
      patterns.
AB  - The plant hormone auxin is a key regulator of plant development, and its uneven
      distribution maintained by polar intercellular auxin transport in plant tissues
      can trigger a wide range of developmental processes. Although the roles of PIN
      FORMED (PIN) proteins in intercellular auxin flow have been extensively
      characterized in Arabidopsis, their roles in woody plants remain unclear. Here, a
      comprehensive analysis of PIN proteins in Populus is presented. Fifteen PINs are
      encoded in the genome of Populus, including four PIN1s, one PIN2, two PIN3s,
      three PIN5s, three PIN6s, and two PIN8s. Similar to Arabidopsis AtPIN proteins,
      PtPINs share conserved topology and transmembrane domains, and are either plasma
      membrane- or endoplasmic reticulum-localized. The more diversified expansion of
      the PIN family in Populus, comparing to that in Arabidopsis, indicates that some
      auxin-regulated developmental processes, such as secondary growth, may exhibit
      unique features in trees. More importantly, different sets of PtoPINs have been
      found to be strongly expressed in the roots, leaves, and cambium in Populus; the
      dynamic expression patterns of selected PtoPINs were further examined during the
      regeneration of shoots and roots. This genome-wide analysis of the Populus PIN
      family provides important cues for their potential roles in tree growth and
      development. 

PMID- 24663344
TI  - Arabidopsis ANGULATA10 is required for thylakoid biogenesis and mesophyll
      development.
AB  - The chloroplasts of land plants contain internal membrane systems, the
      thylakoids, which are arranged in stacks called grana. Because grana have not
      been found in Cyanobacteria, the evolutionary origin of genes controlling the
      structural and functional diversification of thylakoidal membranes in land plants
      remains unclear. The angulata10-1 (anu10-1) mutant, which exhibits pale-green
      rosettes, reduced growth, and deficient leaf lateral expansion, resulting in the
      presence of prominent marginal teeth, was isolated. Palisade cells in anu10-1 are
      larger and less packed than in the wild type, giving rise to large intercellular
      spaces. The ANU10 gene encodes a protein of unknown function that localizes to
      both chloroplasts and amyloplasts. In chloroplasts, ANU10 associates with
      thylakoidal membranes. Mutant anu10-1 chloroplasts accumulate H2O2, and have
      reduced levels of chlorophyll and carotenoids. Moreover, these chloroplasts are
      small and abnormally shaped, thylakoidal membranes are less abundant, and their
      grana are absent due to impaired thylakoid stacking in the anu10-1 mutant.
      Because the trimeric light-harvesting complex II (LHCII) has been reported to be
      required for thylakoid stacking, its levels were determined in anu10-1 thylakoids
      and they were found to be reduced. Together, the data point to a requirement for
      ANU10 for chloroplast and mesophyll development. 

PMID- 24663345
TI  - Internal transcribed spacer 1 secondary structure analysis reveals a common core
      throughout the anaerobic fungi (Neocallimastigomycota).
AB  - The internal transcribed spacer (ITS) is a popular barcode marker for fungi and
      in particular the ITS1 has been widely used for the anaerobic fungi (phylum
      Neocallimastigomycota). A good number of validated reference sequences of
      isolates as well as a large number of environmental sequences are available in
      public databases. Its highly variable nature predisposes the ITS1 for low level
      phylogenetics; however, it complicates the establishment of reproducible
      alignments and the reconstruction of stable phylogenetic trees at higher
      taxonomic levels (genus and above). Here, we overcame these problems by proposing
      a common core secondary structure of the ITS1 of the anaerobic fungi employing a
      Hidden Markov Model-based ITS1 sequence annotation and a helix-wise folding
      approach. We integrated the additional structural information into phylogenetic
      analyses and present for the first time an automated sequence-structure-based
      taxonomy of the ITS1 of the anaerobic fungi. The methodology developed is
      transferable to the ITS1 of other fungal groups, and the robust taxonomy will
      facilitate and improve high-throughput anaerobic fungal community structure
      analysis of samples from various environments. 

PMID- 24663348
TI  - False-positive results from a diagnostic colonoscopy: a teachable moment.

PMID- 24663346
TI  - [Importance of FDG-PET/CT for surgery of rectal cancer].
AB  - BACKGROUND: Examinations using 18F-fluorodeoxyglucose positron emission
      tomography-computed tomography (FDG-PET/CT) are becoming increasingly more
      important in clinical practice for the diagnosis and therapy of cancer patients.
      QUESTION: What role does FDG-PET/CT examination play in the diagnosis and therapy
      of rectal cancer? RESULTS: The FDG-PET/CT method is especially valuable during
      postoperative care when a recurrence is suspected. Especially when tumor marker
      levels rise with no other symptoms, FDG-PET/CT can be used to evaluate unclear
      lesions in the liver and unclear tissue formations at the surgery site and
      distinguish between scar tissue and recurring tumors. Currently, there is
      increasing evidence that a survival prognosis may be possible based on the tracer
      uptake of FDG-PET/CT. There is also a great interest in the possibility of
      evaluating the success of neoadjuvant therapy with FDG-PET/CT. DISCUSSION:
      Despite some limitations FDG-PET/CT plays a significant role in the diagnosis and
      treatment of patients with rectal cancer.

PMID- 24663350
TI  - Improved Monoblock laser brightness using external reflector.
AB  - The Monoblock laser has become the laser of choice in long-range, eye-safe laser
      range finders. It is eye-safe with emission at 1570 nm, high pulse energy, simple
      construction, and high efficiency when pumped by a laser-diode stack. Although
      the output beam divergence of a typical Monoblock with a 3  mm*3  mm cross
      section is relatively large (10-12 mrad), it can be reduced to <1  mrad using a
      telescope with large magnification. In this paper we present a simple and compact
      technique for achieving significant reduction in the Monoblock beam divergence
      using a partial reflector that is placed a short distance from the optical
      parametric oscillator (OPO). Using a 38 mm long Monoblock with a 10 mm long
      potassium titanyl phosphate OPO, we achieved a beam divergence of <4  mrad,
      corresponding to a >2.5* reduction from the unmodified laser. Performance using
      this technique with various feedback and etalon spacings is presented. 

PMID- 24663349
TI  - FOXO4-knockdown suppresses oxidative stress-induced apoptosis of early pro
      angiogenic cells and augments their neovascularization capacities in ischemic
      limbs.
AB  - The effects of therapeutic angiogenesis by intramuscular injection of early pro
      angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in
      the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less
      neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play
      a pivotal role in apoptosis signaling of EPCs in response to oxidative stress.
      Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could
      suppress the oxidative stress-induced apoptosis and augment the
      neovascularization capacity in ischemic limbs. We transfected small interfering
      RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a
      successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to
      hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was
      stronger for the immunodeficient rat ischemic limb tissue than for the rat non
      ischemic one. Although the number of apoptotic EPCs injected into the rat
      ischemic limb was greater than that of apoptotic EPCs injected into the rat non
      ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less
      apoptosis and more neovascularization than EPCs. Taken together, the use of
      FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new
      strategy to augment the effects of therapeutic angiogenesis by intramuscular
      injection of EPCs. 

PMID- 24663352
TI  - Higher-order rocking filters induced mechanically in fibers with different
      birefringence dispersion.
AB  - We studied the transmission characteristics of higher-order rocking filters
      induced mechanically in birefringent microstructured fibers and standard
      elliptical core fibers with varying spectral dependence of phase modal
      birefringence. We demonstrated the effect of birefringence dispersion on
      polarization mode coupling induced by a point-like force. We also investigated
      the spectral dependence of the resonance depth and force-induced resonance
      wavelength shift in mechanical rocking filters. The observed phenomena were
      explained by a numerical model linking the spectral dependence of the
      polarization mode coupling coefficient with the dispersion of intrinsic fiber
      birefringence and applied force. 

PMID- 24663351
TI  - Phase-sensitive narrowband heterodyne holography.
AB  - We report on amplitude and phase imaging of out-of-plane sinusoidal surface
      vibration at nanometer scales with a heterodyne holographic interferometer. The
      originality of the proposed method is to make use of a multiplexed local
      oscillator to address several optical sidebands into the temporal bandwidth of a
      sensor array. This process is called coherent frequency-division multiplexing. It
      enables simultaneous recording and pixel-to-pixel division of sideband holograms,
      which permits quantitative wide-field mapping of optical phase-modulation depths.
      Additionally, a linear frequency chirp ensures the retrieval of the local
      mechanical phase shift of the vibration with respect to the excitation signal.
      The proposed approach is validated by quantitative motion characterization of the
      lamellophone of a musical box, behaving as a group of harmonic oscillators, under
      weak sinusoidal excitation. Images of the vibration amplitude versus excitation
      frequency show the resonance of the nanometric flexural response of one
      individual cantilever, at which a phase hop is measured. 

PMID- 24663353
TI  - Packet error rate analysis of OOK, DPIM, and PPM modulation schemes for ground-to
      satellite laser uplink communications.
AB  - Performance of on-off keying (OOK), digital pulse interval modulation (DPIM), and
      pulse position modulation (PPM) schemes are researched for ground-to-satellite
      laser uplink communications. Packet error rates of these modulation systems are
      compared, with consideration of the combined effect of intensity fluctuation and
      beam wander. Based on the numerical results, performances of different modulation
      systems are discussed. Optimum divergence angle and transmitted beam radius of
      different modulation systems are indicated and the relations of the transmitted
      laser power to them are analyzed. This work can be helpful for modulation scheme
      selection and system design in ground-to-satellite laser uplink communications. 

PMID- 24663354
TI  - Design of a phase-shifting interferometer in the extreme ultraviolet for high
      precision metrology.
AB  - The design of a phase-shift interferometer in the extreme ultraviolet (EUV) is
      described. The interferometer is expected to achieve a significantly higher
      precision as compared with similar instruments that utilize lasers in the visible
      range. The interferometer's design is specifically adapted for its utilization
      with a table top pulsed capillary discharge EUV laser. The numerical model
      evaluates the errors in the interferograms and in the retrieved wavefront induced
      by the shot-to-shot fluctuations and pointing instabilities of the laser. 

PMID- 24663355
TI  - Field correlations of laser arrays in atmospheric turbulence.
AB  - Correlations of the fields at the receiver plane are evaluated after a
      symmetrical radial laser array beam incident field propagates in a turbulent
      atmosphere. The laser array configuration is composed of a number of the same
      size laser beamlets symmetrically located around a ring having a radius that
      determines the distance of the ring from the origin. The variations of the
      correlations of the received field originating from such laser array incidence
      versus the diagonal length starting from a receiver point are examined for
      various laser array parameters, turbulence parameters, and the locations of the
      reception points. Laser array parameters consist of the ring radius and the
      number and size of the beamlets. Structure constant, link length, and wavelength
      are the turbulence parameters whose effects on the field correlation of the laser
      arrays are also investigated. 

PMID- 24663356
TI  - Effect of pore-level geometry on far-field radiative properties of three
      dimensionally ordered macroporous ceria particle.
AB  - The effects of pore size on direction-averaged radiative properties of three
      dimensionally ordered macroporous (3DOM) cerium dioxide (ceria) particles are
      investigated in the spectral range of 0.3-10 MUm. The particles are of spherical
      shape and contain interconnected pores in a face-centered cubic lattice
      arrangement. The porous particle is modeled as a three-dimensional array of
      interacting dipoles using the discrete dipole approximation (DDA). The validity
      of the Lorenz-Mie theory to predict far-field radiative properties of a quasi
      homogeneous particle with the effective optical properties obtained using the
      volume-averaging theory (VAT) is demonstrated. Direction-averaged extinction,
      scattering, and absorption efficiency factors as well as the scattering asymmetry
      factor are determined as a function of the pore size for a particle of 1 MUm
      diameter and as a function of the particle size for pores of 400 nm diameter. The
      overlapping ordered pores in the 3DOM particles and the boundary effects in the
      presence of pores of size comparable to that of the particle are shown to affect
      the radiative properties in the ultraviolet to near-infrared spectral ranges. The
      effects of the 3DOM pore-level features on the far-field radiative properties are
      not captured by the Lorenz-Mie theory combined with VAT. Consequently, the use of
      advanced modeling tools such as DDA is necessary. In the mid- and far-infrared
      spectral ranges, the effects of 3DOM pore-level features on the far-field
      radiative properties diminish and the approach combining the Lorenz-Mie theory
      and VAT is shown to be accurate. 

PMID- 24663357
TI  - Effects of substrate temperatures on the characterization of magnesium fluoride
      thin films in deep-ultraviolet region.
AB  - As a low refractive index material widely used in coatings for deep-ultraviolet
      optical systems, magnesium fluoride (MgF2) films were prepared by electron beam
      evaporation at different substrate temperatures. The effects of the substrate
      temperatures on the optical properties in vacuum and in air, microstructures, and
      composition were investigated, as were the microstructures, their composition,
      and the relation between them. In vacuum, the substrate temperature directly
      affected the microstructures which dominated the packing density and
      inhomogeneity along the film thickness. When the films were exposed to air, the
      refractive index increased and a nonmonotonic change trend of the refractive
      index with substrate temperature was observed due to adsorbed water and magnesium
      oxide (MgO) formed in the film. While a moderate amount of MgO reduced absorption
      loss by decreasing vacancy defects, excessive MgO increased the absorption loss
      because of the high extinction coefficient of the oxide.

PMID- 24663358
TI  - Microwave photonic mixer based on a single bidirectional Mach-Zehnder modulator.
AB  - A microwave photonic mixer based on a single electro-optic Mach-Zehnder intensity
      modulator operating in both directions is presented. In this mixer structure, the
      light from the optical source travels in opposite directions inside the modulator
      and is modulated by both the RF signal and the local oscillator (LO). The output
      optical spectrum comprises the RF signal and LO sidebands without the optical
      carrier. This enables a high conversion efficiency mixing operation to be
      obtained. The mixer has a simple structure, and its performance is insensitive to
      the modulator bias voltage; hence no DC bias voltage and no modulator bias
      controller are required to obtain robust high conversion efficiency mixing
      operation. Experimental results are presented showing large conversion efficiency
      improvement of 25.7 dB compared to the conventional dual Mach-Zehnder modulator
      based microwave photonic mixer and a modulator bias insensitive mixing
      performance. 

PMID- 24663359
TI  - Low scatter and ultra-low reflectivity measured in a fused silica window.
AB  - We investigate the reflectivity and optical scattering characteristics at 1064 nm
      of an antireflection coated fused silica window of the type being used in the
      Advanced LIGO gravitational-wave detectors. Reflectivity is measured in the ultra
      low range of 5-10 ppm (by vendor) and 14-30 ppm (by us). Using an angle-resolved
      scatterometer we measure the sample's bidirectional scattering distribution
      function (BSDF) and use this to estimate its transmitted and reflected scatter at
      roughly 20-40 and 1 ppm, respectively, over the range of angles measured. We
      further inspect the sample's low backscatter using an imaging scatterometer,
      measuring an angle resolved BSDF below 10(-6)  sr-1 for large angles (10 degrees 
      80 degrees  from incidence in the plane of the beam). We use the associated
      images to (partially) isolate scatter from different regions of the sample and
      find that scattering from the bulk fused silica is on par with backscatter from
      the antireflection coated optical surfaces. To confirm that the bulk scattering
      is caused by Rayleigh scattering, we perform a separate experiment measuring the
      scattering intensity versus input polarization angle. We estimate that 0.9-1.3
      ppm of the backscatter can be accounted for by Rayleigh scattering of the bulk
      fused silica. These results indicate that modern antireflection coatings have low
      enough scatter to not limit the total backscattering of thick fused silica
      optics.

PMID- 24663360
TI  - Algorithm research on microstructure distribution on the bottom surface of an
      integrated micro-optical light guide plate.
AB  - Based on the backlight module (BLM) with an integrated micro-optical light guide
      plate (MOLGP) that we proposed [Opt. Express21, 20159 (2013)], an optical model
      that maps the relationship between the distribution of microprisms on the bottom
      surface of the integrated MOLGP and the luminance of the output light is
      established by a backpropagation neural network in this paper. Then the optimized
      distribution of the microprisms for high luminance uniformity of the output light
      is obtained by a genetic algorithm. Finally, the integrated BLM with the
      optimized distribution of microprisms on the bottom surface of the integrated
      MOLGP is set up in optical software, and the simulation results show that the
      luminance uniformity of the output light in this BLM reaches 93%. 

PMID- 24663361
TI  - Compact passively Q-switched Raman laser at 1176  nm and yellow laser at 588  nm
      using Nd3+:YAG/Cr4+:YAG composite crystal.
AB  - Compact passively Q-switched YVO4 first Stokes Raman laser and its frequency
      doubling laser were reported by using Nd3+:YAG/Cr4+:YAG composite crystal for
      what is believed to be the first time. Nanosecond lasers at 1176 and 588 nm were
      obtained. At the incident pump power of 7.84 W, the average output power at 1176
      nm was 423 mW with a pulse width of 1.32 ns and the pulse repetition frequency
      (PRF) of 13.7 kHz. By applying a KTP crystal, an intracavity second harmonic
      generation (SHG) laser at 588 nm also was realized. With an incident pump power
      of 8.95 W, we obtained 105.3 mW average output power of a yellow laser
      corresponding to the pulse width of 4.95 ns and the PRF of 10.75 kHz. In
      addition, the composite crystal efficiently compacted the resonant cavity.

PMID- 24663362
TI  - Digitally reconfigurable complex two-dimensional dual-lattice structure by
      optical phase engineering.
AB  - We present a method to combine two periodic lattice wave fields to generate a
      complex dual-lattice wave field which could be employed for microfabrication of
      corresponding two-dimensional dual-lattice structures. Since the addition of two
      periodic lattice wave fields is coherent in nature, the resultant dual-lattice
      structure is highly dependent on the relative phase difference between
      constituent wave fields. We show that it is possible to have control over the
      dual-lattice pattern by precisely controlling this relative phase difference.
      This control is enabled by making use of digitally addressable phase-only spatial
      light modulator (SLM). We provide the computational method for calculation of the
      corresponding phase mask to be displayed on the SLM and also verify the results
      experimentally by employing a simple 4f Fourier filter-based geometry. The method
      is completely scalable and reconfigurable in terms of the choice of periodic
      lattice wave fields and has the potential to form gradient phase masks which
      could be useful for fabrication of graded-index optical components. 

PMID- 24663363
TI  - 3D display based on parallax barrier with multiview zones.
AB  - A 3D display based on a parallax barrier with multiview zones is proposed. This
      display consists of a 2D display panel and a parallax barrier. The basic element
      of the parallax barrier has three narrow slits. They can show three columns of
      subpixels on the 2D display panel and form 3D pixels. The parallax barrier can
      provide multiview zones. In these multiview zones, the proposed 3D display can
      use a small number of views to achieve a high density of views. Therefore, the
      distance between views is the same as the conventional ones with more views.
      Considering the proposed display has fewer views, which bring more 3D pixels in
      the 3D images, the resolution and brightness will be higher than the conventional
      ones. A 12-view prototype of the proposed 3D display is developed, and it
      provides the same density of views as a conventional one with 28 views.
      Experimental results show the proposed display has higher resolution and
      brightness than the conventional one. The cross talk is also limited at a low
      level. 

PMID- 24663364
TI  - Using acrylamide-based photopolymers for fabrication of holographic optical
      elements in solar energy applications.
AB  - A holographic device is under development that aims to improve light collection
      in solar cells. The aim is to explore the potential of using photopolymer
      holographic optical elements (HOEs) to collect light from a moving source, such
      as the sun, and redirect it for concentration by a holographic lens. A working
      range of 45 degrees  is targeted for such a device to be useful in solar
      applications without tracking. A photopolymer HOE is capable of efficiently
      redirecting light, but the angular selectivity of a single grating is usually of
      the order of one degree at the thicknesses required for high efficiency. The
      challenge here is to increase the angular and wavelength range of the gratings so
      that a reasonable number may be multiplexed and/or combined to create a device
      that can concentrate light incident from a large range of angles. In this paper,
      low spatial frequency holographic recording is explored to increase the angular
      and wavelength range of an individual grating. Ultimately, a combination of
      gratings will be used so that a broad range of angles of incidence are accepted.
      A design is proposed for the combination of such elements into a holographic
      solar collector. The first step in achieving this is optimization of recording at
      low spatial frequency. This requires a photopolymer material with unique
      properties, such as a fast monomer diffusion rate. This paper reports results on
      the efficiency of holograms recorded in an acrylamide-based photopolymer at low
      spatial frequencies (100, 200, and 300  l/mm). The diffraction efficiency and
      angular selectivity of recorded holograms have been studied for various
      photopolymer layer thicknesses and different intensities of the recording beams.
      A diffraction efficiency of over 80% was achieved at a spatial frequency of 200 
      l/mm. The optimum intensity of recording at this spatial frequency was found to
      be 1  mW/cm2. Individual gratings and focusing elements with high efficiency and
      FWHM angles of 3 degrees  are experimentally demonstrated.

PMID- 24663365
TI  - Improved full analytical polygon-based method using Fourier analysis of the three
      dimensional affine transformation.
AB  - Previous research [Appl. Opt.52, A290 (2013)] has revealed that Fourier analysis
      of three-dimensional affine transformation theory can be used to improve the
      computation speed of the traditional polygon-based method. In this paper, we
      continue our research and propose an improved full analytical polygon-based
      method developed upon this theory. Vertex vectors of primitive and arbitrary
      triangles and the pseudo-inverse matrix were used to obtain an affine
      transformation matrix representing the spatial relationship between the two
      triangles. With this relationship and the primitive spectrum, we analytically
      obtained the spectrum of the arbitrary triangle. This algorithm discards low
      level angular dependent computations. In order to add diffusive reflection to
      each arbitrary surface, we also propose a whole matrix computation approach that
      takes advantage of the affine transformation matrix and uses matrix
      multiplication to calculate shifting parameters of similar sub-polygons. The
      proposed method improves hologram computation speed for the conventional full
      analytical approach. Optical experimental results are demonstrated which prove
      that the proposed method can effectively reconstruct three-dimensional scenes. 

PMID- 24663366
TI  - Portable Remote Imaging Spectrometer coastal ocean sensor: design,
      characteristics, and first flight results.
AB  - The design, characteristics, and first test flight results are described of the
      Portable Remote Imaging Spectrometer, an airborne sensor specifically designed to
      address the challenges of coastal ocean remote sensing. The sensor incorporates
      several technologies that are demonstrated for the first time, to the best of our
      knowledge, in a working system in order to achieve a high performance level in
      terms of uniformity, signal-to-noise ratio, low polarization sensitivity, low
      stray light, and high spatial resolution. The instrument covers the 350-1050 nm
      spectral range with a 2.83 nm sampling per pixel, and a 0.88 mrad instantaneous
      field of view, with 608 cross-track pixels in a pushbroom configuration. Two
      additional infrared channels (1240 and 1610 nm) are measured by a spot radiometer
      housed in the same head. The spectrometer design is based on an optically fast
      (F/1.8) Dyson design form coupled to a wide angle two-mirror telescope in a
      configuration that minimizes polarization sensitivity without the use of a
      depolarizer. A grating with minimum polarization sensitivity and broadband
      efficiency was fabricated as well as a slit assembly with black (etched) silicon
      surface to minimize backscatter. First flight results over calibration sites as
      well as Monterey Bay in California have demonstrated good agreement between in
      situ and remotely sensed data, confirming the potential value of the sensor to
      the coastal ocean science community. 

PMID- 24663367
TI  - Flexible diffractive gratings: theoretical investigation of the dependency of
      diffraction efficiency on mechanical deformation.
AB  - The mechanical deformations of variable elastomeric diffractive optical elements
      are calculated by finite element methods. Starting from optimized blazed
      gratings, the derived profile variations serve as an input for rigorous-coupled
      wave analysis to calculate the diffraction efficiency of a spectral band from 200
      to 1200 nm. Applied planar strain of up to 80% has little effect on the maximum
      diffraction efficiency for large grating-period-to-wavelength ratios, g/lambda,
      with only a shift toward shorter wavelengths. With a decreasing g/lambda, the
      maximum efficiency also decreases when stretching the grating structure. Further
      influences of profile design like the angle of the antiblaze facet and the use of
      higher-order blaze profiles were investigated. Finally, we simulate the change in
      the diffraction efficiency at a single wavelength of a flexible blazed grating in
      direct contact with a rigid glass plate. In this case, the soft matter grating is
      compressed and deformed to reduce the diffracting properties. 

PMID- 24663368
TI  - Polymeric-lens-embedded 2D/3D switchable display with dramatically reduced
      crosstalk.
AB  - A two-dimensional/three-dimensional (2D/3D) display system is presented based on
      a twisted-nematic cell integrated polymeric microlens array. This device
      structure has the advantages of fast response time and low operation voltage. The
      crosstalk of the system is analyzed in detail and two approaches are proposed to
      reduce the crosstalk: a double lens system and the prism approach. Illuminance
      distribution analysis proves these two approaches can dramatically reduce
      crosstalk, thus improving image quality. 

PMID- 24663369
TI  - Parameter extraction from fabricated silicon photonic devices.
AB  - Three sets of devices were simulated, designed, and laid out for fabrication in
      the EuroPractice shuttle program and then measured in-house after fabrication. A
      combination of analytical and numerical modeling is used to extract the
      dispersion curves that define the effective index of refraction as a function of
      wavelength for three different classes of silicon photonic devices, namely, micro
      ring resonators, racetrack resonators, and directional couplers. The results of
      this phenomenological study are made plausible by the linearity of the extracted
      dispersion curves with wavelength over the wavelength regime of interest (S and C
      bands) and the use of the determined effective indices to reconstruct the
      measured transmission as a function of wavelength curves in close agreement with
      experiment. The extracted effective indices can be used to place limits on the
      actual fabricated values of waveguide widths, thicknesses, radii of curvature,
      and coupling gaps. 

PMID- 24663370
TI  - High-speed terahertz imaging toward food quality inspection.
AB  - In contrast to conventional x-ray food inspection systems that have difficulty in
      detecting low-density materials, a terahertz imaging system can even identify
      insects and plastics embedded in a food matrix. A reflection-mode continuous-wave
      terahertz imaging system was therefore developed for application to food quality
      inspection, which requires fast, compact, and low-cost detection. High-speed
      operation of the terahertz imaging system was achieved through the use of a beam
      steering tool. A reasonable compromise between the spatial resolution and the
      scan length of an aspheric f-theta scanning lens could be achieved by optimizing
      the lens parameters. 

PMID- 24663371
TI  - Parallelized genetic optimization of spatial light modulator addressing for
      diffractive applications.
AB  - We describe a new technique for optimizing the addressing of spatial light
      modulators in dynamic holographic applications. The method utilizes 200 times
      parallelization using imaging of subholograms in combination with genetic
      optimization. Compared to a fixed linear addressing curve for all different
      gratings, the diffraction efficiency can be improved by up to 25% for a Holoeye
      Pluto LCoS modulator. 

PMID- 24663372
TI  - Effect of coupled graphene oxide on the sensitivity of surface plasmon resonance
      detection.
AB  - We investigated graphene-oxide-(GO-) coupled surface plasmon resonance (SPR)
      detection sensitivity for sandwiched antigen-antibody interaction between human
      and antihuman immunoglobulin G molecules. GO was prepared in a Langmuir-Blodgett
      solution on gold and dielectric surfaces. Theoretical and experimental data
      suggest that an increased dielectric spacer thickness reduces resonance shifts
      for GO-coupled SPR detection as dielectric properties of GO appear to prevail. In
      general, a metal-enhanced structure was shown to provide a larger resonance shift
      by plasmonic field enhancement. The far-field properties were described in terms
      of near-field overlap. The peak resonance shift that was obtained with GO-coupled
      SPR detection was enhanced to 113% of the resonance shift obtained by
      conventional thin-film-based SPR detection and may further be improved by GO
      stacking. 

PMID- 24663373
TI  - Polarized radiative transfer in an arbitrary multilayer semitransparent medium.
AB  - Polarized radiative transfer in a multilayer system is an important problem and
      has wide applications in various fields. In this work, a Monte Carlo (MC) model
      is developed to simulate polarized radiative transfer in a semitransparent
      arbitrary multilayer medium with different refractive indices in each layer. Two
      kinds of polarization mechanisms are considered: scattering by particles and
      reflection and refraction at the Fresnel surfaces or interfaces. The MC method
      has an obvious superiority in that complex mathematical derivations can be
      avoided in solving the polarization by Fresnel reflection and refraction in an
      arbitrary multilayer system. We define the vector radiative transfer matrix
      (VRTM), which describes the polarization characteristics of radiative transfer,
      and obtain four elements of Stokes vector using the VRTM. The results for the two
      layer model by MC method are compared against those for coupled atmosphere-ocean
      model by the discrete-ordinate method available in the literature, which
      validates the correctness of the MC multilayer model of polarized radiative
      transfer. Finally, the results for three-layer, five-layer, and ten-layer models
      are presented in graphical form. Results show that in the multilayer system,
      total reflections occurring at the surfaces/interfaces have significant effects
      on the polarized radiative transfer, which causes abrupt changes or fluctuations
      like waves in the curves of the Stokes vector. 

PMID- 24663374
TI  - Estimating the atmospheric correlation length with stochastic parallel gradient
      descent algorithm.
AB  - The atmospheric turbulence measurement has received much attention in various
      fields due to its effects on wave propagation. One of the interesting parameters
      for characterization of the atmospheric turbulence is the Fried parameter or the
      atmospheric correlation length. We numerically investigate the feasibility of
      estimating the Fried parameter using a simple and low-cost system based on the
      stochastic parallel gradient descent (SPGD) algorithm without the need for
      wavefront sensing. We simulate the atmospheric turbulence using Zernike
      polynomials and employ a wavefront sensor-less adaptive optics system based on
      the SPGD algorithm and report the estimated Fried parameter after compensating
      for atmospheric-turbulence-induced phase distortions. Several simulations for
      different atmospheric turbulence strengths are presented to validate the proposed
      method. 

PMID- 24663375
TI  - Design study of nanograting-based surface plasmon resonance biosensor in the near
      infrared wavelength.
AB  - A key issue with surface plasmon resonance (SPR) biosensors, which are the focus
      of many researchers, is improving their sensitivity to detect lower amounts of
      analyte in a solution. Most SPR developments have focused on the grating-based
      sensitivity-enhancement approach. In addition to sensitivity, a substantial
      enhancement of other sensor characteristics such as resolution and signal-to
      noise ratio (SNR) is desired for designing a practical sensor. So, in this paper,
      the characteristics of surface plasmon polaritons sustained by 1D subwavelength
      metallic gratings on a thin metal slab (under the Krestchmann configuration) have
      been investigated numerically for the analyte-ligand interactions detection.
      Effects of different structural parameters, such as grating period, grating
      depth, metal film thickness, and fill factor have been evaluated on the sensor
      sensitivity as well as resolution and SNR. Numerical results indicate that the
      sensor working in the near-infrared wavelength has a better performance than that
      in the visible one. The result of numerical investigation has been used to design
      an optimized sensor with the best figure of merit. 

PMID- 24663376
TI  - In situ correction of mirror surface to reduce round-trip losses in Fabry-Perot
      cavities.
AB  - High-finesse resonant cavities play an important role in many metrology
      applications such as gravitational wave detectors. The performance of these
      cavities can be limited by round-trip losses (RTP) generated by light that is
      scattered by the mirror surface defects into higher-order modes that are close to
      resonance. In this paper we develop a detailed model of this effect and we study
      possible strategies to correct the mirror surface. We show that it is possible to
      restrict the correction to the combination of a reduced set of surface
      deformations that can be reproduced on the mirror using projected heating
      patterns. We show with an optical simulation that by acting on the cavity mirrors
      it is possible to reduce RTP to the large angle scattering limit. We also show
      that the optimal correction can be computed without any a priori knowledge of the
      mirror surface, but based only on measurements of the power stored inside the
      cavity, thus opening up the possibility of a simple implementation of the
      proposed algorithm. 

PMID- 24663377
TI  - Advanced attenuation and fluorescence measurement methods in the investigation of
      photodarkening and related properties of ytterbium-doped fibers.
AB  - Considering the continuous development of ytterbium (Yb)-doped fibers for fiber
      lasers and amplifiers, thorough characterization of the features and quality of
      such fibers is necessary now more than ever. In particular, the evaluation of the
      very strong core attenuation that results from Yb absorption and the losses
      accompanying photodarkening (PD) processes in Yb-doped optical fibers is still of
      immense interest. Keeping that in mind, the potential of a method using pinhole
      fibers will be demonstrated here. Moreover, the investigation of fluorescence
      properties of Yb3+ is also important; it can be affected by phenomena such as
      reabsorption, inhomogeneous pump intensity distribution, amplified spontaneous
      emission, lasing, and, lastly, PD. As these phenomena occur while measuring the
      fluorescence properties of Yb3+ in optical fibers, they can distort the
      fluorescence spectra and fluorescence decay significantly. We suggest a twice
      perpendicular measurement method and strict time management to avoid these
      interfering phenomena during the fluorescence measurements.

PMID- 24663378
TI  - Analysis of the thickness uniformity improved by using wire masks for coating
      optical bandpass filters.
AB  - Layer uniformity was improved by using a wire mask in the fabrication of a coarse
      wavelength division multiplexer (CWDM) filter. Theoretical simulations determined
      the optimal diameter of the wire to be placed just below the substrate, which was
      rotated at 800 rpm during E-beam evaporation. This simulation also demonstrated
      the correction of the thickness distribution by the etching effect of ion
      assisted deposition. In the corresponding experiment, a distribution uniformity
      of 0.083% in the radial range from 35 to 65 mm was achieved by the coating of the
      CWDM filter. 

PMID- 24663379
TI  - Virtual experiment for near-field goniophotometric measurements.
AB  - Near-field goniometric measurements are employed to determine the photometric
      characteristics of light sources, i.e., the spatial and angular distribution of
      the emitted light. To this end, a complex measurement system consisting of a
      goniometer and a CCD-based imaging photometer is employed. In order to gain
      insight into the measurement system and to enable characterization of the whole
      measurement setup, we propose to apply a computer model to conduct virtual
      experiments. Within the computer model, the current state of all parts of the
      virtual experiment can be easily controlled. The reliability of the computer
      model is demonstrated by a comparison to actual measurement results. As an
      example for the application of the virtual experiment, we present an analysis of
      the impact of axial malpositions of the goniometer and camera. 

PMID- 24663381
TI  - Benign and malignant tumors of the rectum and perirectal region.
AB  - Although most rectal masses are histologically characterized as adenocarcinomas,
      the rectum and perirectal region can be affected by a wide variety of tumors and
      tumor-like conditions that can mimic the symptoms caused by rectal
      adenocarcinoma, including mucosal or submucosal rectal tumors such as lymphoma,
      gastrointestinal stromal tumor, leiomyosarcoma, neuroendocrine tumor, hemangioma,
      and melanoma, as well as tumors of the perirectal region such as developmental
      cyst, neurogenic tumor, osseous tumor, and other miscellaneous conditions. As a
      group, tumors of the rectum are considerably different from the group of tumors
      that arise in the perirectal region: they are most often neoplastic, symptomatic,
      and malignant, whereas tumors arising in the perirectal region are most commonly
      congenital, asymptomatic, and benign. Proctoscopy with biopsy is the most
      important method for the diagnosis of rectal tumors, but this procedure cannot
      determine the precise intramural extension of a rectal tumor and cannot
      accurately distinguish submucosal and intramural tumors from extramural tumors.
      Cross-sectional imaging, especially transrectal ultrasound and magnetic resonance
      imaging, allows evaluation of the entire bowel wall thickness and the perirectal
      tissues, helping further characterize these tumors. Recognition of the existence
      of these masses and their key clinical and imaging features is crucial for
      clinicians to accurately diagnose and appropriately manage these conditions.

PMID- 24663380
TI  - Anoctamin 6 regulates C2C12 myoblast proliferation.
AB  - Anoctamin 6 (Ano6) belongs to a conserved gene family (TMEM16) predicted to code
      for eight transmembrane proteins with putative Ca2+-activated chloride channel
      (CaCC) activity. Recent work revealed that disruption of ANO6 leads to a blood
      coagulation defect and impaired skeletal development. However, its function in
      skeletal muscle cells remains to be determined. By using a RNA interference
      mediated (RNAi) loss-of-function approach, we show that Ano6 regulates C2C12
      myoblast proliferation. Ano6 is highly expressed in C2C12 myoblasts and its
      expression decreases upon differentiation. Knocking down Ano6 significantly
      reduces C2C12 myoblast proliferation but has minimal effect on differentiation.
      Ano6 deficiency significantly reduces ERK/AKT phosphorylation, which has been
      shown to be involved in regulation of cancer cell proliferation by another
      Anoctamin member. Taken together, our data demonstrate for the first time that
      Ano6 plays an essential role in C2C12 myoblast proliferation, likely via
      regulating the ERK/AKT signaling pathway. 

PMID- 24663382
TI  - Interplay Between Conceptual Expectations and Movement Predictions Underlies
      Action Understanding.
AB  - Recent accounts of understanding goal-directed action underline the importance of
      a hierarchical predictive architecture. However, the neural implementation of
      such an architecture remains elusive. In the present study, we used functional
      neuroimaging to quantify brain activity associated with predicting physical
      movements, as they were modulated by conceptual-expectations regarding the
      purpose of the object involved in the action. Participants observed object
      related actions preceded by a cue that generated both conceptual goal
      expectations and movement goal predictions. In 2 tasks, observers judged whether
      conceptual or movement goals matched or mismatched the cue. At the conceptual
      level, expected goals specifically recruited the posterior cingulate cortex,
      irrespectively of the task and the perceived movement goal. At the movement
      level, neural activation of the parieto-frontal circuit, including inferior
      frontal gyrus and the inferior parietal lobe, reflected unpredicted movement
      goals. Crucially, this movement prediction error was only present when the
      purpose of the involved object was expected. These findings provide neural
      evidence that prior conceptual expectations influence processing of physical
      movement goals and thereby support the hierarchical predictive account of action
      processing. 

PMID- 24663383
TI  - Using motor imagery to study the neural substrates of dynamic balance.
AB  - This study examines the cerebral structures involved in dynamic balance using a
      motor imagery (MI) protocol. We recorded cerebral activity with functional
      magnetic resonance imaging while subjects imagined swaying on a balance board
      along the sagittal plane to point a laser at target pairs of different sizes
      (small, large). We used a matched visual imagery (VI) control task and recorded
      imagery durations during scanning. MI and VI durations were differentially
      influenced by the sway accuracy requirement, indicating that MI of balance is
      sensitive to the increased motor control necessary to point at a smaller target.
      Compared to VI, MI of dynamic balance recruited additional cortical and
      subcortical portions of the motor system, including frontal cortex, basal
      ganglia, cerebellum and mesencephalic locomotor region, the latter showing
      increased effective connectivity with the supplementary motor area. The regions
      involved in MI of dynamic balance were spatially distinct but contiguous to those
      involved in MI of gait (Bakker et al., 2008; Snijders et al., 2011; Cremers et
      al., 2012), in a pattern consistent with existing somatotopic maps of the trunk
      (for balance) and legs (for gait). These findings validate a novel, quantitative
      approach for studying the neural control of balance in humans. This approach
      extends previous reports on MI of static stance (Jahn et al., 2004, 2008), and
      opens the way for studying gait and balance impairments in patients with
      neurodegenerative disorders. 

PMID- 24663385
TI  - Polysialylation of NCAM correlates with onset and termination of seasonal
      spermatogenesis in roe deer.
AB  - Roe deer (Capreolus capreolus) are seasonal breeders and cyclic structural
      changes of roe bucks' testis come along with a totally arrested (winter) and a
      highly activated spermatogenesis (summer). For this reason, roe buck represents
      an interesting model to study general mechanisms of initiation and termination of
      spermatogenesis. We investigated if polysialic acid (polySia)-a linear
      homopolymer of alpha2,8-linked sialic acids, which could act as a negative
      regulator of cell-cell adhesion-might be involved in the activation and/or
      inactivation of spermatogenesis. To address this point, testis samples of adult
      male roe deer were collected at different time point of the year. Intriguingly,
      we observed that polySia attached to the neural cell adhesion molecule was
      enhanced during the onset of spermatogenesis in April. In addition, polySia was
      highly expressed in December. Predominantly, polySia was detectable between
      Sertoli cells and spermatogonia in the basal regions of testicular tubules and in
      the adluminal part of Sertoli cells. Interestingly, similar polySia distributions
      were observed during early testis development of other mammalians when gonocytes
      (pre-spermatogonia) and Sertoli cells represent the only cell populations in
      tubuli seminiferi. Thus, polySia is expressed during key steps of the "on/off
      mechanisms" of spermatogenesis and might represent one mediator of the
      interaction and communication between Sertoli cells and germ cell precursors. 

PMID- 24663386
TI  - Precise structural analysis of O-linked oligosaccharides in human serum.
AB  - O-glycans are suitable targets as novel and useful tumor markers. The structures
      of O-glycans in human sera from four healthy controls were precisely analyzed to
      obtain the reference O-glycan database. O-glycans were prepared from sera by
      hydrazine treatment followed by fluorescent labeling with aminopyridine and
      identified using two-dimensional mapping, enzymatic digestion and mass
      spectrometry (MS) together with methanolysis and the use of newly synthesized
      sulfated oligosaccharides as standards. O-glycans, present at more than 0.01% of
      the total O-glycans, were analyzed, and 18 kinds of acidic and 2 kinds of neutral
      glycans were identified. NeuAcalpha2-3Galbeta1-3N-acetylgalactosamine (GalNAc)
      (61-64%), NeuAcalpha2-3Galbeta1-3(NeuAcalpha2-6)GalNAc (15-26%) and Galbeta1
      3GalNAc (6-14%) were major components while other sialylated glycans, Galbeta1
      3(NeuAcalpha2-6)GalNAc, Galbeta1-4GlcNAcbeta1-6(NeuAcalpha2-3Galbeta1-3)GalNAc
      and NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-6(NeuAcalpha2-3Galbeta1-3)GalNAc were
      relatively minor components, accounting for ~1-2%. Very minor glycans accounting
      for ~0.01-0.1% of the total include (i) the neutral glycan, Galbeta1-4GlcNAcbeta1
      6(Galbeta1-3)GalNAc, (ii) sialylated glycans, having sialyl Tn antigen, agalacto
      and trisialylated structures, (iii) fucosylated glycans forming blood type H
      antigen, blood type A antigen, blood type B antigen, Lewis X antigen and sialyl
      Lewis X antigen and (iv) sulfated glycans, having 6-sulfo and 3'-sulfo
      structures. Two kinds of clinically applied tumor markers namely sialyl Tn
      antigen and sialyl Lewis X antigen in healthy controls sera were revealed to be
      present at ~0.1-0.2% of the total. However, other markers such as CA19-9 and DU
      PAN-2 were not found, suggesting the relative amounts of these glycans to be
      <0.01%. These detailed O-glycan profiles will help to find novel carbohydrate
      tumor markers. 

PMID- 24663384
TI  - Heart failure with preserved ejection fraction.
AB  - As part of this series devoted to heart failure (HF), we review the epidemiology,
      diagnosis, pathophysiology, and treatment of HF with preserved ejection fraction
      (HFpEF). Gaps in knowledge and needed future research are discussed. 

PMID- 24663387
TI  - Current state of and needs for hepatitis B screening: results of a large
      screening study in a low-prevalent, metropolitan region.
AB  - BACKGROUND: In low hepatitis B virus (HBV)-prevalent countries, most HBV-infected
      persons are unaware of their status. We aimed to evaluate whether (i) previous
      HBV-testing, (ii) physicians decision to screen, and (iii) CDC's recommendations
      identified infected individuals and which risk-factor groups needing testing.
      METHODS: During a mass, multi-center HBV-screening study from September 2010
      August 2011, 3929 participants were screened for hepatitis B surface antigen
      (HBsAg), anti-HBs and anti-Hepatitis B core antibodies (anti-HBcAb). Questions on
      HBV risk-factors and testing practices were asked to participants, while
      participants' eligibility for HBV-testing was asked to study medical
      professionals. RESULTS: 85 (2.2%) participants were HBsAg-positive, while 659
      (16.8%) had either resolved HBV infection or isolated anti-HBcAb. When comparing
      practices, HBV-testing was more likely to occur in HBV-infected participants if
      Centers for Disease Control and Prevention (CDC) recommendations were used
      (Sensitivity = 100%, 95%CI: 95.8-100) than physicians' discretion (Sensitivity =
      87.1%, 95%CI: 78.0-93.4) or previous HBV-test (Sensitivity = 36.5%, 95%CI: 26.3
      47.6) (p<0.0001). Nevertheless, many non-infected individuals would still have
      been screened using CDC-recommendations (Specificity = 31.1%, 95%CI: 29.6-32.6).
      Using multivariable logistic regression, HBsAg-positive status was significantly
      associated with the following: males, originating from high HBV-endemic region,
      contact with HBV-infected individual, without national healthcare, and
      intravenous-drug user (IDU). Of these risk-factors, physician's discretion for
      testing HBV was not significantly associated with participants' geographical
      origin or IDU. CONCLUSIONS: Missed opportunities of HBV-screening are largely due
      to underestimating country of origin as a risk-factor. Applying CDC
      recommendations could improve HBV-screening, but with the disadvantage of many
      tests. Further development of HBV-testing strategies is necessary, especially
      before severe disease occurs.

PMID- 24663389
TI  - A FAST MAJORIZE MINIMIZE ALGORITHM FOR HIGHER DEGREE TOTAL VARIATION
      REGULARIZATION.
AB  - The main focus of this paper is to introduce a computationally efficient
      algorithm for solving image recovery problems, regularized by the recently
      introduced higher degree total variation (HDTV) penalties. The anisotropic HDTV
      penalty is the fully separable L1 semi-norm of the directional image derivatives;
      the use of this penalty is seen to considerably improve image quality in
      biomedical inverse problems. We introduce a novel majorize minimize algorithm to
      solve the HDTV optimization problem, thus considerably speeding it over the
      previous implementation. Specifically, comparisons with previous iterative
      reweighted algorithm show an approximate ten fold speedup. The new algorithm
      enables us to obtain reconstructions that are free of patchy artifacts exhibited
      by classical TV schemes, while being comparable to state of the art total
      variation regularization schemes in run time.

PMID- 24663388
TI  - How well do discharge diagnoses identify hospitalised patients with community
      acquired infections?--a validation study.
AB  - BACKGROUND: Credible measures of disease incidence, trends and mortality can be
      obtained through surveillance using manual chart review, but this is both time
      consuming and expensive. ICD-10 discharge diagnoses are used as surrogate markers
      of infection, but knowledge on the validity of infections in general is sparse.
      The aim of the study was to determine how well ICD-10 discharge diagnoses
      identify patients with community-acquired infections in a medical emergency
      department (ED), overall and related to sites of infection and patient
      characteristics. METHODS: We manually reviewed 5977 patients admitted to a
      medical ED in a one-year period (September 2010-August 2011), to establish if
      they were hospitalised with community-acquired infection. Using the manual review
      as gold standard, we calculated the sensitivity, specificity, predictive values,
      and likelihood ratios of discharge diagnoses indicating infection. RESULTS: Two
      thousand five hundred eleven patients were identified with community-acquired
      infection according to chart review (42.0%, 95% confidence interval [95%CI]: 40.8
      43.3%) compared to 2550 patients identified by ICD-10 diagnoses (42.8%, 95%CI:
      41.6-44.1%). Sensitivity of the ICD-10 diagnoses was 79.9% (95%CI: 78.1-81.3%),
      specificity 83.9% (95%CI: 82.6-85.1%), positive likelihood ratio 4.95 (95%CI:
      4.58-5.36) and negative likelihood ratio 0.24 (95%CI: 0.22-0.26). The two most
      common sites of infection, the lower respiratory tract and urinary tract, had
      positive likelihood ratios of 8.3 (95%CI: 7.5-9.2) and 11.3 (95%CI: 10.2-12.9)
      respectively. We identified significant variation in diagnostic validity related
      to age, comorbidity and disease severity. CONCLUSION: ICD-10 discharge diagnoses
      identify specific sites of infection with a high degree of validity, but only a
      moderate degree when identifying infections in general.

PMID- 24663391
TI  - [Differential diagnose of angioedema. Acute edematous scleromyxedema].
AB  - A woman presented in the emergency room with the diagnosis of angioedema
      refractory to treatment. She had soft, compressible periorbital edema, as well as
      edema of her hands and lower arms. She also complained of severe pain in her
      hands including sensations of numbness and tingling. The history, course and
      examination results eliminated several possible differential diagnostic
      considerations like an acute histamine- or bradykinin-mediated angioedema or
      superior vena cava syndrome. Histological examination confirmed the diagnosis of
      scleromyxedema. 

PMID- 24663390
TI  - Strong phylogeographic structure in a millipede indicates Pleistocene Vicariance
      between populations on banded iron formations in semi-arid Australia.
AB  - The Yilgarn Banded Iron Formations of Western Australia are topographical
      features that behave as terrestrial islands within the otherwise flat, semi-arid
      landscape. The formations are characterised by a high number of endemic species,
      some of which are distributed across multiple formations without inhabiting the
      intervening landscape. These species provide an ideal context for phylogeographic
      analysis, to investigate patterns of genetic variation at both spatial and
      temporal scales. We examined genetic variation in the spirostreptid millipede,
      Atelomastix bamfordi, found on five of these Banded Iron Formations at two
      mitochondrial loci and 11 microsatellite loci. Strong phylogeographic structuring
      indicated the five populations became isolated during the Pleistocene, a period
      of intensifying aridity in this landscape, when it appears populations have been
      restricted to pockets of moist habitat provided by the formations. The pattern of
      reciprocal monophyly identified within the mtDNA and strong differentiation
      within the nuclear microsatellite data highlight the evolutionary significance of
      these divergent populations and we suggest the degree of differentiation warrants
      designation of each as a conservation unit. 

PMID- 24663392
TI  - [Effective oral immunotherapy for peanut allergy].

PMID- 24663394
TI  - Insulated conducting cantilevered nanotips and two-chamber recording system for
      high resolution ion sensing AFM.
AB  - Biological membranes contain ion channels, which are nanoscale pores allowing
      controlled ionic transport and mediating key biological functions underlying
      normal/abnormal living. Synthetic membranes with defined pores are being
      developed to control various processes, including filtration of pollutants,
      charge transport for energy storage, and separation of fluids and molecules.
      Although ionic transport (currents) can be measured with single channel
      resolution, imaging their structure and ionic currents simultaneously is
      difficult. Atomic force microscopy enables high resolution imaging of nanoscale
      structures and can be modified to measure ionic currents simultaneously.
      Moreover, the ionic currents can also be used to image structures. A simple
      method for fabricating conducting AFM cantilevers to image pore structures at
      high resolution is reported. Tungsten microwires with nanoscale tips are
      insulated except at the apex. This allows simultaneous imaging via cantilever
      deflections in normal AFM force feedback mode as well as measuring localized
      ionic currents. These novel probes measure ionic currents as small as picoampere
      while providing nanoscale spatial resolution surface topography and is suitable
      for measuring ionic currents and conductance of biological ion channels. 

PMID- 24663395
TI  - Relationship of supernatural beliefs and first treatment contact in patients with
      obsessive compulsive disorder: an exploratory study from India.
AB  - BACKGROUND: The etiology of mental illness has been attributed to many different
      causes by people of various cultural backgrounds, including supernatural beliefs.
      This in turn affects the help-seeking behavior. Aim of this study was to explore
      the supernatural belief and pathways of care in patients with obsessive
      compulsive disorder (OCD) attending a tertiary care hospital located in north
      India. METHODOLOGY: In all, 89 consecutive patients diagnosed with OCD (according
      to the International Classification of Diseases-10th Revision (ICD-10)) and >= 15
      years of age were evaluated for their supernatural belief and help seeking.
      RESULTS: More than half of the patients (54%) believed in supernatural causes and
      57.3% attributed their illness to supernatural causes. In addition to
      supernatural causes, many patients also attributed their illness to stress
      (household/work-related stress) or chemical imbalance in the body and or mind.
      About two-thirds of the patients (n = 58; 65.2%) first contacted a psychiatrist
      for their symptoms of OCD. Those who first contacted faith healers believed in
      one of the supernatural causations. CONCLUSION: Patients with OCD hold multiple
      beliefs regarding the etiology and treatment of mental illness which can affect
      their pathways to care.

PMID- 24663396
TI  - Mediators and moderators of long-term effects of violent video games on
      aggressive behavior: practice, thinking, and action.
AB  - IMPORTANCE: Although several longitudinal studies have demonstrated an effect of
      violent video game play on later aggressive behavior, little is known about the
      psychological mediators and moderators of the effect. OBJECTIVE: To determine
      whether cognitive and/or emotional variables mediate the effect of violent video
      game play on aggression and whether the effect is moderated by age, sex, prior
      aggressiveness, or parental monitoring. DESIGN, SETTING, AND PARTICIPANTS: Three
      year longitudinal panel study. A total of 3034 children and adolescents from 6
      primary and 6 secondary schools in Singapore (73% male) were surveyed annually.
      Children were eligible for inclusion if they attended one of the 12 selected
      schools, 3 of which were boys' schools. At the beginning of the study,
      participants were in third, fourth, seventh, and eighth grades, with a mean (SD)
      age of 11.2 (2.1) years (range, 8-17 years). Study participation was 99% in year
      1. MAIN OUTCOMES AND MEASURES: The final outcome measure was aggressive behavior,
      with aggressive cognitions (normative beliefs about aggression, hostile
      attribution bias, aggressive fantasizing) and empathy as potential mediators.
      RESULTS: Longitudinal latent growth curve modeling demonstrated that the effects
      of violent video game play are mediated primarily by aggressive cognitions. This
      effect is not moderated by sex, prior aggressiveness, or parental monitoring and
      is only slightly moderated by age, as younger children had a larger increase in
      initial aggressive cognition related to initial violent game play at the
      beginning of the study than older children. Model fit was excellent for all
      models. CONCLUSIONS AND RELEVANCE: Given that more than 90% of youths play video
      games, understanding the psychological mechanisms by which they can influence
      behaviors is important for parents and pediatricians and for designing
      interventions to enhance or mitigate the effects.

PMID- 24663397
TI  - Flaps for closure of soft tissue defects in infected revision knee arthroplasty.
AB  - PURPOSE: Total knee arthroplasty revision has wound healing deficits of up to 20
      %. Defects in the knee region of multimorbid patients are hard to treat as
      complete explantation and revision arthroplasty is often too burdensome for them.
      In this study, we present our results with flaps for the treatment of defects
      after knee replacement, arthrodesis or osteosynthesis. METHODS: Twenty-five
      patients (26 knees) with defects in the knee region were treated with flaps. Mean
      follow-up was 37 months (13-61) and the patients had a mean age of 72 years (49
      85). A total of 39 flaps were performed (27 muscle flaps, seven fascio-cutaneous
      flaps and five free flaps). RESULTS: Patients with more than three comorbidities
      showed higher risk of complications after surgery. Fifteen patients showed no
      infection at last follow up. Five patients received an arthrodesis of the knee,
      two showed persistent infection of the implant with fistula, and three were
      amputated above the knee. CONCLUSIONS: Amputation could be avoided in 22 cases
      (85 %). The gastrocnemius muscle flap showed good results in the treatment of
      defects after arthroplasty or arthrodesis of the knee in multimorbid patients.
      This procedure can be used if further revision surgery is not indicated.

PMID- 24663398
TI  - Autologous osteochondral transplantation for the treatment of knee lesions:
      results and limitations at two years' follow-up.
AB  - PURPOSE: Focal chondral and osteochondral knee lesions are a common condition,
      particularly hard to treat, and often involve young active patients with high
      expectations in terms of symptomatic relief and return to sports. Autologous
      osteochondral transplantation allows the defect area to be restored with hyaline
      cartilage. The aim of this study is to analyse whether it represents a safe and
      effective treatment option for small-medium-sized knee chondral and osteochondral
      lesions in a young and active population. METHODS: Thirty-one patients (18 men,
      13 women; mean age 32 +/- ten; mean BMI 24 +/- 3) affected by focal knee chondral
      and osteochondral lesions were enrolled and treated with autologous osteochondral
      transplantation. They were prospectively followed-up for 24 months with the IKDC
      subjective, IKDC-objective, and Tegner scores. Adverse events and failures were
      also reported, as well as the Bandi score to detect symptoms from the donor area.
      RESULTS: A significant increase was reported in all the clinical scores adopted.
      In particular, the IKDC-subjective score increased from a basal value of 40.3 +/-
      16.2 to 62.6 +/- 18.0 at the 12 months' evaluation, with a further significant
      increase up to 71.6 +/- 20.5 at the final 24 months' follow-up (p < 0.0005). A
      positive trend was also found by analysing the IKDC-objective score. The Tegner
      score revealed a significant improvement from a basal value of 2.2 +/- 1.8 to 3.7
      +/- 1.5 at the final evaluation (p = 0.003), although it was not possible to
      regain the same pre-injury sports activity level of 5.0 +/- 2.2. Two failures
      were reported. The Bandi score revealed patients complaining of mild and moderate
      symptoms, not correlated to the lesion size. The presence of symptoms ascribable
      to the donor area was significantly correlated with a lower clinical outcome.
      CONCLUSIONS: Autologous osteochondral transplantation proved to be, at short-term
      evaluation, a suitable option to treat small-medium sized chondral and
      osteochondral lesions. However, clinical improvement is slow and a significant
      percentage of patients develop symptoms attributable to the donor area, thus
      reducing the overall benefit of this procedure.

PMID- 24663400
TI  - Depth refuge and the impacts of SCUBA spearfishing on coral reef fishes.
AB  - In recent decades, spearfishing with SCUBA has emerged as an efficient method for
      targeting reef fish in deeper waters. However, deeper waters are increasingly
      recognised as a potential source of refuge that may help sustain fishery
      resources. We used a combination of historical catch data over a 20-year time
      period and fishery-independent surveys to investigate the effects of SCUBA
      spearfishing on coral reef fish populations in the southern Mariana Islands. Two
      jurisdictions were studied; Guam, where SCUBA spearfishing is practiced, and the
      nearby Commonwealth of Northern Mariana Islands (CNMI), where SCUBA spearfishing
      has been banned since 2003. Fishery-independent data were collected using baited
      remote underwater stereo-video systems (stereo-BRUVs) stratified by depth, marine
      protected area status and jurisdiction. Herbivores (primary consumers) dominated
      spearfishing catches, with parrotfish (scarines) and surgeonfish/unicornfish
      (acanthurids) the main groups harvested. However, the large, endangered humphead
      wrasse (Cheilinus undulatus) was the main species by weight landed by SCUBA
      spearfishers. SCUBA spearfishing was associated with declining size of scarines
      over time and catches shifting from a dominance of large parrotfishes to a mixed
      assemblage with increasing proportions of acanthurids. Comparisons between Guam
      and the nearby CNMI revealed differences in the assemblage of fished species and
      also greater size of scarines and acanthurids in deep water where SCUBA fishing
      is banned. These results suggest that SCUBA spearfishing impacts reef fish
      populations and that the restriction of this fishing method will ensure refuge
      for fish populations in deeper waters. We recommend a ban on SCUBA spearfishing
      to preserve or aid the recovery of large, functionally important coral reef
      species and to improve the sustainability of coral reef fisheries. 

PMID- 24663399
TI  - Development of an innovative 3D cell culture system to study tumour--stroma
      interactions in non-small cell lung cancer cells.
AB  - INTRODUCTION: We describe a novel 3D co-culture model using non-small cell lung
      cancer (NSCLC) cell lines in combination with lung fibroblasts. This model allows
      the investigation of tumour-stroma interactions and addresses the importance of
      having a more in vivo like cell culture model. METHODS: Automation-compatible
      multi-well hanging drop microtiter plates were used for the production of 3D mono
      and co-cultures. In these hanging drops the two NSCLC cell lines A549 and
      Colo699 were cultivated either alone or co-cultured with lung fibroblasts. The
      viability of tumour spheroids was confirmed after five and ten days by using
      Annexin V/Propidium Iodide staining for flow-cytometry. Tumour fibroblast
      spheroid formation was characterized by scanning electron microscope (SEM), semi
      thin sections, fluorescence microscope and immunohistochemistry (IHC). In
      addition to conventional histology, protein expression of E-Cadherin, vimentin,
      Ki67, fibronectin, cytokeratin 7 and alpha-smooth muscle actin (alpha-SMA) was
      investigated by IHC. RESULTS: Lower viability was observed in A549 monocultures
      compared to co-cultures, whereas Colo699 monocultures showed better viability
      compared to co-cultures. Ki67 expression varied significantly between mono- and
      co-cultures in both tumour cell lines. An increase of vimentin and decreased E
      Cadherin expression could be detected during the course of the cultivation
      suggesting a transition to a more mesenchymal phenotype. Furthermore, the
      fibroblast cell line showed an expression of alpha-SMA only in co-culture with
      the cancer cell line A549, thereby indicating a mesenchymal to mesenchymal shift
      to an even more myofibroblast phenotype. CONCLUSION: We demonstrate that our
      method is a promising tool for the generation of tumour spheroid co-cultures.
      Furthermore, these spheroids allow the investigation of tumour-stroma
      interactions and a better reflection of in vivo conditions of cancer cells in
      their microenvironment. Our method holds potential to contribute to the
      development of anti-cancer agents and support the search for biomarkers.

PMID- 24663401
TI  - Dynamic trapping and two-dimensional transport of swimming microorganisms using a
      rotating magnetic microrobot.
AB  - Manipulation of microorganisms with intrinsic motility is a challenging yet
      important task for many biological and biomedical applications. Currently, such a
      task has only been accomplished using optical tweezers, while at the risk of
      averse heating and photodamage of the biological samples. Here, we proposed a new
      micro-robotic approach for fluidic trapping and two-dimensional transportation of
      motile microorganisms near a solid surface in fluids. We demonstrated selective
      trapping and transportation of individual freely swimming multi-flagellated
      bacteria over a distance of 30 MUm (7.5 body length of the carrier) on a surface,
      using the rotational flows locally induced by a rotating magnetic microparticle.
      Only a weak uniform magnetic field (<3 mT) was applied to actuate the
      microparticle. The microparticle can translate on a glass substrate by rotating
      at a speed of up to 100 MUm s(-1), while providing a fluidic force of a few to
      tens of pico-Newtons. 

PMID- 24663402
TI  - Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart
      failure.
AB  - RATIONALE: Long noncoding RNAs represent a novel class of molecules regulating
      gene expression. Long noncoding RNAs are present in body fluids, but their
      potential as biomarkers was never investigated in cardiovascular disease.
      OBJECTIVE: To study the role of long noncoding RNAs as potential biomarkers in
      heart disease. METHODS AND RESULTS: Global transcriptomic analyses were done in
      plasma RNA from patients with or without left ventricular remodeling after
      myocardial infarction. Regulated candidates were validated in 3 independent
      patient cohorts developing cardiac remodeling and heart failure (788 patients).
      The mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) was downregulated early
      after myocardial infarction but upregulated during later stages. LIPCAR levels
      identified patients developing cardiac remodeling and were independently to other
      risk markers associated with future cardiovascular deaths. CONCLUSIONS: LIPCAR is
      a novel biomarker of cardiac remodeling and predicts future death in patients
      with heart failure.

PMID- 24663404
TI  - Diode-end-pumped continuously tunable single frequency Tm, Ho:LLF laser at 2.06
      MUm.
AB  - We report on a laser diode-end-pumped continuously tunable single frequency Tm,
      Ho:LLF laser near room temperature. For transmission of 5%, the maximum single
      frequency output power of 221 mW at 2064.4 nm was obtained by using two uncoated
      etalons. The single frequency Tm, Ho:LLF laser operated on the fundamental
      transverse mode with an M2 factor of 1.13, and the output frequency could be
      tuned continuously near 1.5 GHz by angle tuning only of the 1 mm thick etalon.
      Furthermore, the influence of output coupler transmission on the laser
      performance was also investigated. The single frequency laser can be used as a
      seed laser for coherent Doppler lidar and differential absorption lidar systems.

PMID- 24663403
TI  - Hypertriglyceridemic waist phenotype and chronic kidney disease in a Chinese
      population aged 40 years and older.
AB  - OBJECTIVE: To examine the relationship between the HW phenotype and risk for CKD
      in a community population aged 40 years and older. METHODS: A cross-sectional
      study was conducted in Zhuhai from June to October 2012. The participants were
      divided into three groups: Group 1, Waist circumference >90 cm in men or >85 cm
      in women and triglycerides >=2 mmol/l; Group 3, Waist circumference <=90 cm in
      men or <=85 cm in women and triglycerides <2 mmol/l; Group 2, The remaining
      participants. The prevalence of the three subgroups and CKD were determined. The
      association between HW phenotype and CKD was then analyzed using SPSS (version
      13.0). RESULTS: After adjusting for age and sex, Group 1 was associated with CKD
      (OR 3.08, 95% CI 2.01, 4.73, P<0.001), when compared with Group 3. Further
      adjustment for factors which were potential confounders and unlikely to be in the
      causal pathway between the HW phenotype and CKD, Group 1 was still significantly
      associated with CKD. The OR for CKD was 2.65 (95% CI 1.65, 4.26, P<0.001). When
      adjusted for diabetes and hypertension, the association of Group 1 and CKD was
      still significant (OR 2.09, 95% CI 1.26, 3.45, P = 0.004). Group 2 was associated
      with CKD (OR 1.81, 95% CI 1.29, 2.53, P = 0.001), when compared with Group 3.
      Further adjustment for factors which were potential confounders, Group 2 was
      still significantly associated with CKD. The OR for CKD was 1.75 (95% CI 1.22,
      2.51, P = 0.002). When adjusted for diabetes and hypertension, the association
      between Group 2 and CKD still existed. The OR for CKD was 1.48 (95% CI 1.01,
      2.16, P = 0.046). CONCLUSION: Our results showed that HW phenotype was associated
      with CKD in the population aged 40 years and older.

PMID- 24663405
TI  - Orthogonal coding methods for increasing the number of multiplexed channels in
      coherent beam combining.
AB  - We introduce orthogonally coded modulations for active coherent beam combining
      (CBC), and show how using Walsh codes enables the increase of the number of
      combined channels. Analytical, numerical, and experimental results are presented
      and compared to the standard multifrequency dithering technique, demonstrating
      that at least 5 times more fibers can be combined using the same modulation
      frequency. The modulation format excluded, no particular changes in the system
      need to be introduced and the benefits of active coherent beam combing, such as
      atmospheric turbulence compensation capability, are kept unchanged. Finally, we
      point out that this approach can be applied in partially CBC. 

PMID- 24663406
TI  - High-efficiency backlight module with two guiding modes.
AB  - We propose a design for a high-efficiency backlight module that does not require
      a brightness enhancement film (BEF). With the high-efficiency backlight module it
      is possible to achieve almost the same half-luminance angle as a conventional
      edge-lit backlight module can achieve. The backlight system is comprised of a
      crisscross light guide plate (LGP) and one diffuser sheet. The crisscross LGP is
      composed of a LGP and optically patterned film (OPF). The backlight module allows
      light to be extracted through the direct guiding mode and top guiding mode,
      respectively. We controlled arrangement of the microstructures to increase the
      optical efficiency and the uniformity by two modes. Compared to the conventional
      edge-lit backlight module, there is a two-fold improvement in both the total
      optical efficiency and on-axis luminance with the high-efficiency backlight
      module. 

PMID- 24663407
TI  - All-optical buffer using nonlinear polarization rotation effect of gain
      transparent semiconductor optical amplifier.
AB  - A cascaded all-optical buffer with large dynamic delay based on polarization
      rotation of a gain-transparent semiconductor optical amplifier is proposed and
      demonstrated. The analysis and experimental results indicate that the pulse
      distortion and pattern effect can be fully improved, and the amplified
      spontaneous emission noise accumulation can be inhibited effectively as well; the
      data packets are stored for six round-trips in buffering units 1 and 2,
      respectively, corresponding to a delay time as long as 33 MUs. The proposed
      buffering scheme can be regarded as an effective reference to the study work of
      all-optical buffer.

PMID- 24663408
TI  - Evaluation of polarized terahertz waves generated by Cherenkov phase matching.
AB  - We report terahertz (THz) wave generation by satisfying Cherenkov phase-matching
      condition in both s and p polarizations. A dual-wavelength optical parametric
      oscillator is constructed from two potassium titanium oxide phosphate crystals
      pumped by a frequency-doubled Nd:YAG laser. By rotating the orientation of both a
      lithium niobate crystal (LiNbO3) and the polarization of the pump waves, the
      polarization of the THz wave changes. Due to the difference in the refractive
      index and absorption, the output power for p polarization is one tenth that for s
      polarization. A tuning range from 0.2 to 6.5 THz is obtained for s polarization,
      and from 0.2 to 4.2 and 5.4 to 6.9 THz for p polarization. The extraction
      efficiency is improved by changing the angle of prism for p polarization, and a
      large phase change occurs at total internal reflection. Consequently, p-polarized
      THz waves are optimal for spectroscopic applications.

PMID- 24663409
TI  - Simulation and analysis of adjacency effects in coastal waters: a case study.
AB  - A methodology has been developed and applied to accurately quantify and analyze
      adjacency effects in satellite ocean color data for a set of realistic and
      representative observation conditions in the northern Adriatic Sea. The procedure
      properly accounts for sea surface reflectance anisotropy, off-nadir views,
      coastal morphology, and atmospheric multiple scattering. The study further
      includes a sensitivity analysis on commonly applied approximations. Results
      indicate that, within the accuracy limits defined by the radiometric resolution
      of ocean color sensors, adjacency effects in coastal waters might be significant
      at both visible and near-infrared wavelengths up to several kilometers off the
      coast. These results additionally highlight a significant dependence on the angle
      of observation, on the directional reflectance properties of the sea surface, and
      on the atmospheric multiple scattering. 

PMID- 24663410
TI  - Large-aperture, equal-path interferometer for precision measurements of flat
      transparent surfaces.
AB  - The measurement of flat optical components often presents difficulties because
      the presence of parallel surfaces generates multiple reflections that confuse
      conventional laser-based interferometers. These same parts have increasingly
      demanding surface finish tolerances as technologies improve over time, further
      complicating the metrology task. Here we describe an interferometric optical
      system for high-accuracy noncontact evaluation of the form and texture of
      precision flat surfaces based on an equal-optical-path geometry that uses
      extended, broadband illumination to reduce the influence of speckle noise,
      multiple reflections, and coherent artifacts by a factor of 10 when compared to
      laser-based systems. Combined with a low-distortion, fixed-focus imaging system
      and 4-Mpixel camera, the 100 mm aperture instrument offers surface height
      resolutions of 0.1 nm over lateral spatial frequencies extending from 0.01 to 10
      cycles/mm. The instrument is vibration resistant for production-line testing of
      flat optics such as glass hard disks for the data-storage industry and flat-panel
      display substrates.

PMID- 24663411
TI  - Coherence scanning interferometry: measurement and correction of three
      dimensional transfer and point-spread characteristics.
AB  - When applied to the measurement of smooth surfaces, coherence scanning
      interferometry can be described by a three-dimensional linear filtering operation
      that is characterized either by the point-spread function in the space domain or
      equivalently by the transfer function (TF) in the spatial frequency domain. For
      an ideal, aberration-free instrument, these characteristics are defined uniquely
      by the numerical aperture of the objective lens and the bandwidth of the
      illumination source. In practice, however, physical imperfections such as those
      in lens aberrations, reference focus, and source alignment mean that the
      instrument performance is not ideal. Currently, these imperfections often go
      unnoticed as the instrument performance is typically only verified using
      rectilinear artifacts such as step heights and lateral grids. If an object of
      varying slope is measured, however, significant errors are often observed as the
      surface gradient increases. In this paper, a new method of calibration and
      adjustment using a silica micro-sphere as a calibration artifact is introduced.
      The silica microsphere was used to compute the point-spread and TF
      characteristics of the instrument, and the effect of these characteristics on
      instrument performance is discussed. Finally, a straightforward method to correct
      for phase and amplitude imperfections in the TF is described using a modified
      inverse filter. 

PMID- 24663412
TI  - Ho3+Yb3+-codoped germanate-tellurite glasses for 2.0 MUm emission performance.
AB  - 2.0 MUm emission property of a new germanate-tellurite (GT) glass with Ho3+/Yb3+
      codoping is synthesized and analyzed. Efficient 2.0 MUm emission of Ho3+ ions
      sensitized by Yb3+ ions from the host glass was observed under 980 nm pumping.
      Based on the measured absorption spectra, the Judd-Ofelt parameters were
      calculated and discussed. The maximum emission cross section of Ho3+ ions
      transition is 4.36*10(-21) cm2 around 2.0 MUm. The energy transfer efficiency is
      calculated and fitted the decay signals. The good spectroscopic properties
      suggest that Ho3+/Yb3+-codoped GT glass may become an attractive host for
      developing solid state lasers operating in the mid-infrared.

PMID- 24663413
TI  - Large aperture at low cost three-dimensional time-of-flight range sensor using
      scanning micromirrors and synchronous detector switching.
AB  - In this article the problem of achieving fast scanning of a time-of-flight range
      sensor with a large optical receiver aperture at low system cost is targeted. The
      presented approach to solve this problem consists of a micromirror-based
      transmitter unit and a receiver unit consisting of a large aperture lens system
      with a small field of view and a detector array. A concept, which is called
      synchronous detector switching, is applied to the detector array. Thereby
      electronic steering of the small receiver field of view is possible. The overall
      approach is compared to alternative approaches, and the underlying concept of
      synchronous detector switching is demonstrated experimentally in an
      implementation of a three-dimensional time-of-flight range sensor. It is
      theoretically shown that the presented concept is potentially cheaper than the
      alternative approaches for applications with a field of view of less than 60*60
      degrees . After a discussion of the strengths and limitations of the approach,
      its effect on broader scientific issues is outlined. 

PMID- 24663414
TI  - Cascaded four-wave mixing seeded by two continuous wave signals.
AB  - We report on the broadband-cascaded four-wave mixing (CFWM) products generated in
      a photonic crystal fiber pumped by a picosecond pulse and seeded by two
      continuous wave (CW) signals. The equal and unequal frequency spaced CFWM
      products could be obtained through continuously tuning one of the CW wavelengths.
      Among the equally spaced CFWM products, the smallest frequency spacing was 477
      GHz. The influences of the Raman scattering and the third-order dispersion on the
      CFWM were also discussed.

PMID- 24663416
TI  - Holographic volume displacement calculations via multiwavelength digital
      holography.
AB  - In this work multiwavelength digital holography is applied to calculate the
      volume displacement of various topographic surface features. To accurately
      measure the volume displacement of macroscopic features, long synthetic
      wavelengths up to several millimeters are generated using tunable IR laser
      sources. Practical methods of implementation are considered, including geometric
      effects of both Michelson and Mach-Zehnder recording configurations and error due
      to wavelength selection. 

PMID- 24663415
TI  - Humidity and pressure sensor based on internal reflection.
AB  - A low-cost humidity and pressure optical sensor, based on the internal reflection
      phenomenon, is presented. It takes advantage of the phase difference acquired by
      s- and p-polarized light undergoing internal reflection to generate an easily
      detectable minimum in the reflected profile, in a position corresponding to the
      critical angle. The apparatus presents good sensitivity to relative humidity
      changes above 70% and a response time below one second. The same device is also
      capable of measuring changes in pressure and can be used as a vacuum gauge
      between 1 and 1000 mbar.

PMID- 24663417
TI  - Plasmon-induced transparency in metal-insulator-metal waveguide side-coupled with
      multiple cavities.
AB  - We have demonstrated the analogue of electromagnetically induced transparency
      (EIT) in the metal-insulator-metal plasmonic waveguide, which consists of a bus
      waveguide side-coupled with a series of slot cavities. By finite-difference time
      domain simulations, it is found that the resonance wavelength of the slot cavity
      can be controlled by adjusting the length of the cavity. Moreover, the EIT-like
      response is strongly dependent on the coupling separation between the
      corresponding adjacent cavities. Multiple-peak plasmon-induced transparency can
      be realized by cascading multiple cavities with different lengths and suitable
      cavity-cavity separations. This ultracompact plasmonic waveguide system may find
      important applications for multichannel plasmonic filter, nanoscale optical
      switching, and slow-light devices in highly integrated optical circuits and
      networks. 

PMID- 24663418
TI  - Experimental study on modified linear quadratic Gaussian control for adaptive
      optics.
AB  - To achieve high-resolution imaging the standard control algorithm used for
      classical adaptive optics (AO) is the simple but efficient proportional-integral
      (PI) controller. The goal is to minimize the rms error of the residual wave
      front. However, using the PI controller, it is not possible to do this. One
      possible way to minimize the rms error is to use linear quadratic Gaussian (LQG)
      control. In practice, however, this control algorithm still encounters an
      unexpected problem that leads to the divergence of control in AO. This paper
      proposes a modified LQG (MLQG) to solve this issue. The controller is analyzed
      explicitly. Laboratory tests shows strong stability and high precision compared
      to the classical control. 

PMID- 24663419
TI  - Elasto-optic effect anisotropy in strontium borate crystals.
AB  - The anisotropy of piezo- and elasto-optic effects in strontium borate crystals
      was studied by the indicative surfaces method. The geometry of acousto-optic
      interaction with maximum efficiency was found on the basis of the surface maxima
      of the elasto-optic effect. 

PMID- 24663420
TI  - Generation of second-order vortex arrays with six-pinhole interferometers under
      plane wave illumination.
AB  - We propose a method based on six-pinhole interferometers to generate vortex
      arrays with topological charge 2, only with plane wave illumination. The six
      pinhole interferometer is composed of two concentric symmetrical three-pinhole
      interferometers with different radial distances of the pinholes and a relative
      rotation of 60 deg from each other. In the Fourier domain, the vortices with
      second-order topological charge are generated when the radial distances of the
      two three-pinhole interferometers satisfy some certain ratios. Due to the
      symmetry of the six-pinhole interferometer, such vortices are distributed at the
      vertices of some symmetrically distributed regular hexagons. The experimental
      results obtained in a focal-to-focal system show satisfactory coincidence with
      the calculations.

PMID- 24663421
TI  - Detection of carcinogenic chromium in synthetic hair dyes using laser induced
      breakdown spectroscopy.
AB  - A laser induced breakdown spectroscopic (LIBS) system, consisting of a pulsed 266
      nm laser radiation, in conjunction with a high-resolution spectrograph, a gated
      intensified charge coupled device camera, and a built-in delay generator were
      used to develop a sensitive detector to quantify the concentration of toxic
      substances such as chromium in synthetic hair dyes available on the local market.
      The strong atomic transition line of chromium (Cr I) at 427.5 nm wavelength was
      used as a fingerprint wavelength to calibrate the detection system and also to
      quantify the levels of chromium in the hair dye samples. The limit of detection
      achieved by our LIBS detection system for chromium was 1.2 ppm, which enabled us
      to detect chromium concentration in the range of 5-11 ppm in the commercial hair
      dyes available on the local market. The concentrations of chromium in the hair
      dyes measured using our system were validated using a standard analytical
      technique such as inductively coupled plasma mass spectrometry (ICPMS), and
      acceptable agreement (nearly 8%) was found between the results obtained by the
      two methods (LIBS and ICPMS). This study is highly significant for human health,
      specifically for people using synthetic hair dyes for changing the color of their
      hair.

PMID- 24663422
TI  - Accurate and practical method for characterizing Laguerre-Gaussian modes.
AB  - We propose a new parameter, Q(p,l)(2), based on cross-sectional intensity
      distribution to distinguish Laguerre-Gaussian (LG) beams. Theoretically,
      Q(p,l)(2) shows an approximately linear dependence on the topological index in
      higher LG modes. Compared with the similar parameter Q(p,l) proposed by Long et
      al. [Opt. Lett.38, 3047 (2013)] recently, our experimental result demonstrates
      that the approximate linearity of Q(p,l)(2) brings out the advantage in
      characterizing higher topological indices. In addition, as more intensity data is
      used in calculating Q(p,l)(2), the experimental error is diminished naturally.
      Thus, Q(p,l)(2) can be used to easily and accurately characterize LG modes.

PMID- 24663423
TI  - Time evolution of a Gaussian class of quasi-distribution functions under
      quadratic Hamiltonian.
AB  - A Lie algebraic method for propagation of the Wigner quasi-distribution function
      (QDF) under quadratic Hamiltonian was presented by Zoubi and Ben-Aryeh. We show
      that the same method can be used in order to propagate a rather general class of
      QDFs, which we call the "Gaussian class." This class contains as special cases
      the well-known Wigner, Husimi, Glauber, and Kirkwood-Rihaczek QDFs. We present
      some examples of the calculation of the time evolution of those functions. 

PMID- 24663424
TI  - Optical filter with tunable wavelength and bandwidth based on phototunable
      cholesteric liquid crystals.
AB  - An optical filter with tunable wavelength and bandwidth is demonstrated using two
      phototunable cholesteric liquid crystals (CLCs) configured in a reflection mode.
      In this mode, incident light is first reflected by one Azo-chiral-doped CLC and
      then by another one. The tuning mechanism, which is based on the pitch modulation
      of the CLCs that contain an Azo-chiral dopant, can be controlled by two pumping
      laser beams. The central wavelength can be tuned from 510 to 628 nm, and the
      bandwidth can be changed from 13 to 79 nm.

PMID- 24663425
TI  - Thin film characterization for modeling and optimization of silver-dielectric
      color filters.
AB  - We investigate the most appropriate way to optically characterize the materials
      and predict the spectral responses of metal-dielectric filters in the visible
      range. Special attention is given to thin silver layers that have a major impact
      on the filter's spectral transmittance and reflectance. Two characterization
      approaches are compared, based either on single layers, or on multilayer stacks,
      in approaching the filter design. The second approach is preferred, because it
      gives the best way to predict filter characteristics. Meanwhile, it provides a
      stack model and dispersion relations that can be used for filter design
      optimization. 

PMID- 24663426
TI  - Nonlinear optical security system based on a joint transform correlator in the
      Fresnel domain.
AB  - A new optical security system for image encryption based on a nonlinear joint
      transform correlator (JTC) in the Fresnel domain (FrD) is proposed. The proposal
      of the encryption process is a lensless optical system that produces a real
      encrypted image and is a simplified version of some previous JTC-based encryption
      systems. We use a random complex mask as the key in the nonlinear system for the
      purpose of increasing the security of the encrypted image. In order to retrieve
      the primary image in the decryption process, a nonlinear operation has to be
      introduced in the encrypted function. The optical decryption process is
      implemented through the Fresnel transform and the fractional Fourier transform.
      The security system proposed in this paper preserves the shift-invariance
      property of the JTC-based encryption system in the Fourier domain, with respect
      to the lateral displacement of the key random mask in the decryption process.
      This system shows an improved resistance to chosen-plaintext and known-plaintext
      attacks, as they have been proposed in the cryptanalysis of the JTC encrypting
      system. Numerical simulations show the validity of this new optical security
      system. 

PMID- 24663427
TI  - Solar tomography adaptive optics.
AB  - Conventional solar adaptive optics uses one deformable mirror (DM) and one guide
      star for wave-front sensing, which seriously limits high-resolution imaging over
      a large field of view (FOV). Recent progress toward multiconjugate adaptive
      optics indicates that atmosphere turbulence induced wave-front distortion at
      different altitudes can be reconstructed by using multiple guide stars. To
      maximize the performance over a large FOV, we propose a solar tomography adaptive
      optics (TAO) system that uses tomographic wave-front information and uses one DM.
      We show that by fully taking advantage of the knowledge of three-dimensional wave
      front distribution, a classical solar adaptive optics with one DM can provide an
      extra performance gain for high-resolution imaging over a large FOV in the near
      infrared. The TAO will allow existing one-deformable-mirror solar adaptive optics
      to deliver better performance over a large FOV for high-resolution magnetic field
      investigation, where solar activities occur in a two-dimensional field up to
      60'', and where the near infrared is superior to the visible in terms of magnetic
      field sensitivity.

PMID- 24663428
TI  - Numerically focused full-field swept-source optical coherence microscopy with low
      spatial coherence illumination.
AB  - We propose a 3D imaging technique based on the combination of full-field swept
      source optical coherence microscopy (FF-SSOCM) with low spatial coherence
      illumination and a special numerical processing that allows for numerically
      focused coherent-noise-free imaging without mechanical scanning in longitudinal
      or transversal directions. We show, both theoretically and experimentally, that
      the blurring effects arising in FF-SSOCM due to defocus can be corrected by
      appropriate numerical processing even when low spatial coherence illumination is
      used. A FF-SSOCM system was built for testing the performance of this technique.
      Coherent-noise-free imaging of a sample with longitudinal extent exceeding the
      optical depth of field is demonstrated without displacement of the sample or any
      optical element. 

PMID- 24663429
TI  - Detection of trace elements in nondegradable organic spent clay waste using
      optimized dual-pulsed laser induced breakdown spectrometer.
AB  - The detection of trace elements present in nondegradable organic spent clay waste
      has been carried out using an optimized dual-pulsed laser induced breakdown
      spectrometer. The two laser pulses at 1064 and 266 nm were collinearly collimated
      and focused on the sample surface in order to enhance the signal intensity. The
      atomic transition lines at 568.8 nm (Na-I), 504.2 nm (Pb-II), 405.8 nm (Pb -I),
      443.56 nm (Ca-I), 469.41 nm (S-I), 520.8 nm (Cr-I), 643 nm (Cd-I), and 928.1 nm
      (Cl-I) were used as marker wavelengths, and the concentrations of 688, 300, 204,
      460, and 2440 ppm of Pb, S, Cd, Cr, and Cl, respectively, were detected in the 5%
      spent clay in the binder. The limits of detection of Pb, S, Cd, Cr, and Cl were
      estimated to be 6.7, 17.2, 6.5, 5.1, and 14.8 ppm, respectively, from the
      calibration curve for each element. In order to confirm the reliability of our
      system, the concentrations of the reported elements detected using our system
      were compared to the ones obtained with inductively coupled plasma emission
      spectroscopy and found to be in good agreement.

PMID- 24663430
TI  - Human oral cancer cells with increasing tumorigenic abilities exhibit higher
      effective membrane capacitance.
AB  - OBJECTIVE: Although cells with tumorigenic/stem cell-like properties have been
      identified in many cancers, including oral squamous cell carcinoma (OSCC), their
      isolation and characterisation is still at early stages. The aim of this study is
      to characterise the electrophysiological properties of OSCC cells with different
      tumorigenic properties in order to establish if a correlation exists between
      tumorigenicity and cellular electrical characteristics. MATERIALS AND METHODS:
      Rapid adherence to collagen IV was used as a non-invasive, functional method to
      isolate subsets of cells with different tumorigenic abilities from one oral
      dysplastic and three OSCC-derived cell lines. The cell subsets identified and
      isolated using this method were further investigated using dielectrophoresis, a
      label-free method to determine their electrophysiological parameters. Cell
      membrane morphology was investigated using scanning electron microscopy (SEM) and
      modulated by use of 4-methylumbelliferone (4-MU). RESULTS: Rapid adherent cells
      (RAC) to collagen IV, enriched for increased tumorigenic ability, had
      significantly higher effective membrane capacitance than middle (MAC) and late
      (LAC) adherent cells. SEM showed that, in contrast to MAC and LAC, RAC displayed
      a rough surface, extremely rich in cellular protrusions. Treatment with 4-MU
      dramatically altered RAC membrane morphology by causing loss of filopodia, and
      significantly decreased their membrane capacitance, indicating that the highest
      membrane capacitance found in RAC was due to their cell membrane morphology.
      CONCLUSION: This is the first study showing that OSCC cells with higher tumour
      formation ability exhibit higher effective membrane capacitance than cells that
      are less tumorigenic. OSSC cells with different tumorigenic ability possessed
      different electrophysiological properties mostly due to their differences in the
      cell membrane morphology. These results suggest that dielectrophoresis could
      potentially used in the future for reliable, label-free isolation of putative
      tumorigenic cells.

PMID- 24663431
TI  - Understanding the psychosocial and environmental factors and barriers affecting
      utilization of maternal healthcare services in Kalomo, Zambia: a qualitative
      study.
AB  - This qualitative study aimed to identify psychosocial and environmental factors
      contributing to low utilization of maternal healthcare services in Kalomo,
      Zambia. Twelve focus group discussions (n = 141) and 35 in-depth interviews were
      conducted in six health centre catchment areas. Focus group discussions comprised
      women of reproductive age (15-45 years), who gave birth within the last year; in
      depth interviews comprised traditional leaders, mothers, fathers, community
      health workers and nurse-midwives. Perspectives on maternal health complications,
      health-seeking behaviour and barriers to utilization of maternal healthcare were
      explored. Most women showed insight into maternal health complications.
      Nevertheless, they started antenatal care visits late and did not complete the
      recommended schedule. Moreover, most women gave birth at home and did not use
      postnatal care. The main reasons for the low utilization were the low perceived
      quality of maternal healthcare services in clinics (negative attitude), negative
      opinion of important referents (subjective norms), physical and economic barriers
      such as long distances, high transport and indirect costs including money for
      baby clothes and other requirements. To improve, our findings suggest need for an
      integrated intervention to mitigate these barriers. Our findings also suggest
      need for further research to measure the elicited beliefs and determine their
      relevance and changeability. 

PMID- 24663432
TI  - Tree cover bimodality in savannas and forests emerging from the switching between
      two fire dynamics.
AB  - Moist savannas and tropical forests share the same climatic conditions and occur
      side by side. Experimental evidences show that the tree cover of these ecosystems
      exhibits a bimodal frequency distribution. This is considered as a proof of
      savanna-forest bistability, predicted by dynamic vegetation models based on non
      linear differential equations. Here, we propose a change of perspective about the
      bimodality of tree cover distribution. We show, using a simple matrix model of
      tree dynamics, how the bimodality of tree cover can emerge from the switching
      between two linear dynamics of trees, one in presence and one in absence of fire,
      with a feedback between fire and trees. As consequence, we find that the
      transitions between moist savannas and tropical forests, if sharp, are not
      necessarily catastrophic. 

PMID- 24663433
TI  - Red Si-rhodamine drug conjugates enable imaging in GFP cells.
AB  - Here we evaluated a series of Si-derivatized rhodamine (SiR) dyes for their
      ability to visualize a model drug in live cells. We show that a charge neutral
      SiR derivative (but not others) can indeed be used to follow the intracellular
      location of the model therapeutic drug in GFP cells. 

PMID- 24663436
TI  - Validation and evaluation of the volumetric measurement of cerebellopontine angle
      cistern as a prognostic factor of microvascular decompression for primary
      trigeminal neuralgia.
AB  - BACKGROUND: The aim of this study was to analyze the prognostic factors of
      trigeminal neuralgia (TN) after microvascular decompression (MVD), and to
      evaluate the volumetric parameters of the cerebellopontine angle (CPA) cistern as
      a pathogenic factor and imaging predictor. METHODS: This retrospective study
      included 70 patients with primary TN treated with pure MVD, followed up for at
      least 1 year and evaluated by high-resolution MR imaging. The volume of the CPA
      cistern was calculated bilaterally, and the "Cistern Deviation Index" was defined
      to represent degree of deviation of the CPA cistern. Clinical data and volumetric
      parameters were compared between patients with TN and age- and sex-matched
      controls without TN, and between the recurrent and non-recurrent patients.
      RESULTS: The transposition procedure had a better outcome than the interposition
      procedure (P < 0.001). There was a significant difference in the volume of CPA
      cistern between the affected and unaffected side (152.1 +/- 50.1 vs. 179.9 +/-
      63.7 mm(3), P < 0.001) in patients with TN, while no significant difference
      between the right and left side (158.7 +/- 44.6 vs. 163.1 +/- 49.8 mm(3), P =
      0.162) in controls. The Cistern Deviation Index was significantly larger in
      controls than in patients with TN (P = 0.048), and in the non-recurrent patients
      than in recurrent patients (P = 0.040). CONCLUSION: We demonstrated that the
      volumetric parameters of the CPA cistern are a marker for understanding the
      pathogenesis of TN and useful for predicting the recurrence after MVD. The
      Cistern Deviation Index might contribute to deciding the surgical approach.

PMID- 24663435
TI  - Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus
      murinus), using ultra-high-performance liquid chromatography-quadrupole time of
      flight.
AB  - The grey mouse lemur (Microcebus murinus) is a non-human primate used to study
      the ageing process. Resveratrol is a polyphenol that may increase lifespan by
      delaying age-associated pathologies. However, no information about resveratrol
      absorption and metabolism is available for this primate. Resveratrol and its
      metabolites were qualitatively and quantitatively analyzed in male mouse-lemur
      plasma (after 200 mg.kg-1 of oral resveratrol) by ultra-high performance liquid
      chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass
      spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion
      common to resveratrol and all its metabolites: m/z 227.072, and an ion common to
      dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to
      identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two
      monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and
      glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro
      resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both
      sulfo- and glucurono-conjugated derivatives). The presence of such metabolites
      has been already detected in the mouse, rat, pig, and humans. Free resveratrol
      was measurable for several hours in mouse-lemur plasma, and its two main
      metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3
      sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma
      collection, while its hydrophilic metabolites were present at 24 h after intake.
      These data will help us interpret the effect of resveratrol in mouse lemurs and
      provide further information on the inter-species characteristics of resveratrol
      metabolism. 

PMID- 24663437
TI  - Letter to the editor: dural reconstruction with a vascularised pleural flap
      following en bloc resection of a thoracic epithelioid sarcoma: technical note.

PMID- 24663439
TI  - [Benzodiazepine hypnotics, zolpidem and zopiclone on private prescriptions: use
      between 1993 and 2012].
AB  - OBJECTIVE: Previous analyses showed that benzodiazepine hypnotics as well as
      zolpidem and zopiclone (Z drugs) were increasingly being dispensed on so-called
      private prescriptions (Privatverordnungen) in Germany. Any doctor can provide
      private prescriptions for prescription drugs which are fully funded by the
      patient. This study aimed to analyze the amount of private prescriptions for
      hypnotics over the last 20 years. METHODS: We compared utilization data from
      statutory health insurance claims with purchasing statistics from community
      pharmacies for the years 1993-2012. RESULTS: From 1993 to 2012 purchased packages
      of hypnotics decreased (from 14.9 to 9.9 million). Benzodiazepines were dispensed
      less and Z drugs more often. In 2012 zopiclone (4.3 million packages of which
      42.7 % were private prescriptions), zolpidem (3.6 million, 57.6 %) and
      lormetazepam (0.8 million, 57.8 %) were most often prescribed. CONCLUSION: Trends
      in prescribing Z drugs are particularly noticeable whereby zolpidem was dispensed
      more often on private prescriptions than zopiclone. This seems to be further
      evidence for a higher dependence and abuse potential of zolpidem.

PMID- 24663438
TI  - Discovery of the elusive leptin in birds: identification of several 'missing
      links' in the evolution of leptin and its receptor.
AB  - Leptin is a pleiotropic protein best known for regulation of appetite and fat
      storage in mammals. While many leptin orthologs have been identified among
      vertebrates, an authentic leptin in birds has remained elusive and controversial.
      Here we identify leptin sequence from the Peregrine falcon, Falco peregrinus
      (pfleptin), and identify sequences from two other birds (mallard and zebra
      finch), and 'missing' vertebrates (elephant shark, alligator, Indian python,
      Chinese soft-shelled turtle, and coelacanth). The pattern of genes surrounding
      leptin (snd1, rbm28) is syntenic between the falcon and mammalian genomes.
      Phylogenetic analysis of all known leptin protein sequences improves our
      understanding of leptin's evolution. Structural modeling of leptin orthologs
      highlights a highly conserved hydrophobic core in the four-helix cytokine packing
      domain. A docked model of leptin with the leptin receptor for Peregrine falcon
      reveals several conserved amino acids important for the interaction and possible
      coevolution of leptin with its receptor. We also show for the first time, an
      authentic avian leptin sequence that activates the JAK-STAT signaling pathway.
      These newly identified sequences, structures, and tools for avian leptin and its
      receptor will allow elucidation of the function of these proteins in feral and
      domestic birds. 

PMID- 24663440
TI  - Serum vitamin D insufficiency is related to blood pressure in diabetic pregnancy.
AB  - BACKGROUND: Vitamin D deficiency in pregnancy has been associated with an
      increased risk of preeclampsia. However, the association between serum vitamin D
      and blood pressure in pregnant women has been scarcely evaluated, particularly in
      women with a high risk of developing hypertensive disorders of pregnancy. We
      sought to evaluate the association between serum 25-hydroxyvitamin D and blood
      pressure in pregnant women with gestational diabetes mellitus (GDM). METHODS: A
      cohort of 184 pregnant women with GDM was followed during the third trimester of
      pregnancy and early puerperium. Blood pressure was recorded in all prenatal
      visits, and serum vitamin D was measured by chemiluminescence immunoassay.
      Pearson's coefficients and multiple linear regressions were used to study
      predictors of blood pressure levels. RESULTS: Women with vitamin D insufficiency
      (<30ng/mL; n = 159) had higher systolic and diastolic blood pressure than the
      remaining participants. In white women (n = 136), serum vitamin D levels
      presented a significant negative correlation with systolic blood pressure at the
      beginning (r = -0.268; P = 0.002) and at the end of the third trimester (r = 
      0.203; P = 0.02), and vitamin D significantly affected systolic blood pressure
      after adjusting for confounders. This was not observed in women of other
      ethnicities. CONCLUSIONS: In this cohort of pregnant women with GDM, vitamin D
      insufficiency was associated with higher blood pressure, and in white women,
      serum vitamin D was an independent predictor of systolic blood pressure during
      pregnancy.

PMID- 24663441
TI  - A chimeric transcript containing Psy1 and a potential mRNA is associated with
      yellow flesh color in tomato accession PI 114490.
AB  - Carotenoid content is the primary determinant of fruit color that affects
      nutritional value and appearance in tomato. Phytoene synthase (PSY) is the key
      regulatory enzyme in the carotenoid biosynthesis pathway. Absent function of PSY1
      in tomato fruit results in yellow flesh phenotype. We, here, report that two
      different transcripts, a wild-type (Psy1) and a chimeric mRNA (Psy1/Unknown),
      exist in a yellow-fruited tomato accession PI 114490. Psy1/Unknown is generated
      by joining exons from two different genes, Psy1 and an unknown gene, transcribed
      using both complementary DNA strands. The Psy1 shows low expression in the fruit
      of PI 114490, while the expression of Psy1/Unknown in the fruit of PI 114490
      shows the same pattern as Psy1 in red fruit. The PSY1/Unknown has a lower
      function than PSY1 in a bacterial expression system. Coincidence of one single
      nucleotide polymorphism (SNP) in the fourth intron and one simple sequence repeat
      (SSR) with 19 AT repeats in the downstream sequence of Psy1 gene with
      Psy1/Unknown in a set of yellow-fruited tomato lines indicates that Psy1/Unknown
      might be caused by the SNP and/or SSR. One possible explanation of these
      observations is trans-splicing. Severely reduced Psy1 transcript caused by
      Psy1/Unknown results in low accumulation of carotenoid and yellow flesh in PI
      114490. 

PMID- 24663443
TI  - The design of contact lens based ocular drug delivery systems for single-day use:
      Part (I) Structural factors, surrogate ophthalmic dyes and passive diffusion
      studies.
AB  - The poor retention and efficacy of instilled drops as a means of delivering drugs
      to the ophthalmic environment is well-recognised. The potential value of contact
      lenses as a means of ophthalmic drug delivery, and consequent improvement of pre
      corneal retention is one obvious route to the development of a more effective
      ocular delivery system. Furthermore, the increasing availability and clinical use
      of daily disposable contact lenses provides the platform for the development of
      viable single-day use drug delivery devices based on existing materials and
      lenses. In order to provide a basis for the effective design of such devices, a
      systematic understanding of the factors affecting the interaction of individual
      drugs with the lens matrix is required. Because a large number of potential
      structural variables are involved, it is necessary to achieve some
      rationalisation of the parameters and physicochemical properties (such as
      molecular weight, charge, partition coefficients) that influence drug
      interactions. Ophthalmic dyes and structurally related compounds based on the
      same core structure were used to investigate these various factors and the way in
      which they can be used in concert to design effective release systems for
      structurally different drugs. Initial studies of passive diffusional release form
      a necessary precursor to the investigation of the features of the ocular
      environment that over-ride this simple behaviour. Commercially available contact
      lenses of differing structural classifications were used to study factors
      affecting the uptake of the surrogate actives and their release under 'passive'
      conditions. The interaction between active and lens material shows considerable
      and complex structure dependence, which is not simply related to equilibrium
      water content. The structure of the polymer matrix itself was found to have the
      dominant controlling influence on active uptake; hydrophobic interaction with the
      ophthalmic dye playing a major role. 

PMID- 24663442
TI  - Genetic structure of duckweed population of Spirodela, Landoltia and Lemna from
      Lake Tai, China.
AB  - Duckweed is widely used in environmental biotechnology and has recently emerged
      as a potential feedstock for biofuels due to its high growth rate and starch
      content. The genetic diversity and composition of a natural duckweed population
      in genera Spirodela, Landoltia and Lemna from Lake Tai, China, were investigated
      using probabilistic analysis of multilocus sequence typing (MLST). The 78 strains
      were categorized into five lineages, among which strains representing L.
      aequinoctialis and S. polyrhiza were predominant. Among the five lineages,
      interlineage transfers of markers were infrequent and no recombination was
      statistically detected. Tajima's D tests determined that all loci are subject to
      population bottlenecks, which is likely one of the main reasons for the low
      genetic diversity observed within the lineages. Interestingly, strains of L.
      turionifera are found to contain small admixture from L. minor, providing rare
      evidence of transfer of genetic materials in duckweed. This was discussed with
      respect to the hypothesis that a cross of these two gave rise to L. japonica.
      Moreover, the conventional maximum-likelihood phylogenetic analysis clearly
      recognized all the species in the three genera with high bootstrap supports. In
      conclusion, this work offers a basic framework for using MLST to characterize
      Spirodela, Landoltia and in particular Lemna strains at the species level, and to
      study population genetics and evolution history of natural duckweed populations.

PMID- 24663445
TI  - Googling Self-injury: the state of health information obtained through online
      searches for self-injury.
AB  - IMPORTANCE: Nonsuicidal self-injury (NSSI), the deliberate destruction of one's
      body tissue without suicidal intent, is a significant issue for many youth.
      Research suggests that adolescents and emerging adults prefer the Internet as a
      means to retrieve NSSI resources and that important others (eg, caregivers) may
      also seek this information online. To our knowledge, no research to date has
      examined the quality of health information regarding NSSI on the Internet.
      OBJECTIVES: To examine the scope and nature of web searches for NSSI websites and
      to evaluate the quality of health-information websites found via these online
      searches. DESIGN, SETTING, AND PARTICIPANTS: Ninety-two NSSI-related search terms
      were identified using the Google AdWords Keywords program. The first page of
      Google search results for each term was content-analyzed for website type and
      health-information websites were further coded for credibility, NSSI myth
      propagation, and quality of health information. MAIN OUTCOMES AND MEASURES:
      Frequency of NSSI web searches and indices of health information quality.
      RESULTS: Nonsuicidal self-injury-related search terms were sought more than 42
      million times in the past year and health-information websites were the most
      common website type found (21.5%). Of these, a health and/or academic institution
      endorsed only 9.6%. At least one NSSI myth was propagated per website, including
      statements that NSSI indicates a mental disorder (49.3%), a history of abuse
      (40%), or the notion that primarily women self-injure (37%). The mean quality of
      health information score on these websites was 3.49 (SD = 1.40) of 7. CONCLUSIONS
      AND RELEVANCE: Nonsuicidal self-injury-related search terms are frequently sought
      out worldwide and are likely to yield noncredible and low-quality information
      that may propagate common NSSI myths. These data suggest health professionals
      need to be aware of what information is online and should refer young patients
      and their families to reliable online resources to enhance NSSI literacy. Efforts
      to facilitate people's access to credible NSSI resources via the Internet are
      also needed.

PMID- 24663444
TI  - Over-expression of a rice tau class glutathione s-transferase gene improves
      tolerance to salinity and oxidative stresses in Arabidopsis.
AB  - Glutathione S-transferases (GSTs) are multifunctional proteins encoded by large
      gene family in plants, which play important role in cellular detoxification of
      several endobiotic and xenobiotic compounds. Previously, we suggested the diverse
      roles of rice GST gene family members in plant development and various stress
      responses based on their differential expression. In this study, we report the
      functional characterization of a rice tau class GST gene, OsGSTU4. OsGSTU4 fusion
      protein was found to be localized in nucleus and cytoplasm. The over-expression
      of OsGSTU4 in E. coli resulted in better growth and higher GST activity under
      various stress conditions. Further, we raised over-expression transgenic
      Arabidopsis plants to reveal its in planta function. These transgenic lines
      showed reduced sensitivity towards plant hormones, auxin and abscisic acid.
      Various analyses revealed improved tolerance in transgenic Arabidopsis plants
      towards salinity and oxidative stresses, which may be attributed to the lower
      accumulation of reactive oxygen species and enhanced GST activity. In addition,
      microarray analysis revealed up-regulation of several genes involved in stress
      responses and cellular detoxification processes in the transgenic plants as
      compared to wild-type. These results suggest that OsGSTU4 can be used as a good
      candidate for the generation of stress-tolerant crop plants. 

PMID- 24663446
TI  - Timing parameter optimization for comparison experiments of TSIM.
AB  - The optimization problem of an absolute radiometer's timing parameters is
      investigated for comparison experiments of Total Solar Irradiance Monitor (TSIM).
      Comparison experiments were performed to establish the TSIM's contact with other
      space radiometers for measuring total solar irradiance (TSI). Since the
      comparison experiments had to be performed on a tight schedule under the impact
      of weather conditions, the measurement parameters for the comparison experiments
      were selected carefully using optimized solutions of timing parameters. The
      optimized solutions were identified by a genetic algorithm (GA) based on a
      thermal model of an absolute radiometer. The thermal model includes terms of heat
      radiation, air conduction, etc. Fitness value function and constraints of GA are
      constructed using the thermal model. The experimental results indicate that the
      selected measurement parameters are sufficient to implement accurate calibration
      of TSI, providing more opportunities for solar observation. 

PMID- 24663447
TI  - Cryogenic infrared filter made of alumina for use at millimeter wavelength.
AB  - We propose a high-thermal-conductivity infrared filter using alumina for
      millimeter-wave detection systems. We constructed a prototype two-layer
      antireflection-coated alumina filter with a diameter of 100 mm and a thickness of
      2 mm and characterized its thermal and optical properties. The transmittance of
      this filter at 95 and 150 GHz is 97% and 95%, respectively, while the estimated 3
      dB cut-off frequency is at 450 GHz. The high thermal conductivity of alumina
      minimizes thermal gradients. We measure a differential temperature of only 0.21 K
      between the center and the edge of the filter when it is mounted on a thermal
      anchor of 77 K. We also constructed a thermal model based on the prototype filter
      and analyzed the scalability of the filter diameter. We conclude that the
      temperature increase at the center of the alumina IR filter is less than 6 K,
      even with a large diameter of 500 mm, when the temperature at the edge of the
      filter is 50 K. This is suitable for an application to a large-throughput next
      generation cosmic-microwave-background polarization experiment such as POLARBEAR
      2.

PMID- 24663448
TI  - Interferometry technique to eliminate noise in interference data based on a Mach
      Zehnder interferometer.
AB  - Some experiments based on interferometry, such as studying refractive index
      changes, need a long time to be completed, and any movement or oscillation in the
      order of wavelength during that time may wash out the interference fringes or at
      least reduce the quality of the interferogram. In this work, a new technique is
      presented to enhance the interferometric data during such experiments. The main
      idea behind this technique is the use of a reference beam to monitor all
      surrounding changes during the experiment. Laser light was divided into two
      parallel beams and then entered into a Mach-Zehnder interferometer. One of the
      beams was used as a reference signal to measure interferometer drift and the
      other one was passed through the sample to measure the refractive index changes
      simultaneously in a single interferometer. Noise was extracted from the data with
      a written computer code to achieve a noise-free output. 

PMID- 24663449
TI  - Application of 3D digital image correlation to track displacements and strains of
      canvas paintings exposed to relative humidity changes.
AB  - This paper introduces a methodology for tracking displacements in canvas
      paintings exposed to relative humidity changes. Displacements are measured by
      means of the 3D digital image correlation method that is followed by a
      postprocessing of displacement data, which allows the separation of local
      displacements from global displacement maps. The applicability of this
      methodology is tested on measurements of a model painting on canvas with
      introduced defects causing local inhomogeneity. The method allows the evaluation
      of conservation methods used for repairing canvas supports. 

PMID- 24663450
TI  - Two-dimensional temperature measurements in particle loaded technical flames by
      filtered Rayleigh scattering.
AB  - Filtered Rayleigh scattering (FRS) is applied to determine two-dimensional
      temperature distributions in a hexamethyldisiloxane loaded propane/air flame
      intended for combustion chemical vapor deposition processes. An iodine cell as a
      molecular filter suppresses background scattering, e.g., by particles, while the
      wings of the spectrally broadened Rayleigh scattering can pass this filter. A
      frequency-doubled Nd:YAG laser is tuned to a strong absorption line of iodine.
      The gas temperature is deduced from the transmitted Rayleigh scattering signal.
      Since FRS also depends on molecule-specific scattering cross sections, the local
      gas composition of majority species is measured using the Raman scattering
      technique. Limits and restrictions are discussed. 

PMID- 24663451
TI  - Shaping the surface of Borofloat 33 glass with ultrashort laser pulses and a
      spatial light modulator.
AB  - We demonstrate an application of a liquid-crystal-based spatial light modulator
      (LC-SLM) for the parallel generation of optically smooth structured surfaces on
      Borofloat 33 glass. In this work, the picosecond laser beam intensity profile of
      wavelength 515 nm is spatially altered by a LC-SLM, and then delivered to the
      workpiece in order to generate surface deformations whose shape corresponds to
      the image generated by the LC display. To ensure that localized melting occurs
      without ablation, the glass surface is covered by a thin layer of graphite prior
      to laser treatment to provide increased linear absorption of the laser light.
      After laser treatment the residual graphite layer is removed using methanol and
      the whole sample is annealed for 1 h at a temperature of 560  degrees C, making
      the laser-induced surface deformations optically smooth.

PMID- 24663452
TI  - Lateral integration of vertical-cavity surface-emitting laser and slow light
      Bragg reflector waveguide devices.
AB  - We present the modeling and the experiment on the lateral integration of a
      vertical-cavity surface-emitting laser (VCSEL) and slow light Bragg reflector
      waveguide devices. The modeling shows an efficient direct-lateral coupling from a
      VCSEL to an integrated slow light waveguide. The calculated result shows a
      possibility of 13 dB chip gain and an extinction ratio over 5 dB for a compact
      slow light semiconductor optical amplifier (SOA) and electroabsorption modulator
      integrated with a VCSEL, respectively. We demonstrate an SOA-integrated VCSEL,
      exhibiting the maximum output power over 6 mW. Also, we fabricate a sub-50-MUm
      long electroabsorption modulator laterally integrated with a VCSEL. An extinction
      ratio of over 15 dB for a voltage swing of 2.0 V is obtained without noticeable
      change of threshold. In addition, we demonstrate an on-chip electrothermal beam
      deflector integrated with a VCSEL.

PMID- 24663453
TI  - Flexible mask illumination setup for serial multipatterning in Talbot
      lithography.
AB  - A flexible illumination system for Talbot lithography is presented, in which the
      Talbot mask is illuminated by discrete but variable incidence angles. Changing
      the illumination angle stepwise in combination with different exposure doses for
      different angles offers the possibility to generate periodic continuous surface
      relief structures. To demonstrate the capability of this approach, two exemplary
      micro-optical structures were manufactured. The first example is a blazed grating
      with a stepsize of 1.5 MUm. The second element is a specific beam splitter with
      parabolic-shaped grating grooves. The quality of the manufacturing process is
      evaluated on the basis of the optical performance of the resulting micro-optical
      elements.

PMID- 24663454
TI  - Three-dimensional micro-diffraction modeling.
AB  - Squared elementary cells with correlated radiant point sources are presented as
      basic structures for characterizing the propagation of the field emitted by two
      dimensional planar sources of any shape and in arbitrary state of spatial
      coherence. The field is transported on a finite expansion of nonparaxial modes,
      whose propagation in the micro-diffraction domain is discussed under both the
      diffraction and the interference conditions. 

PMID- 24663455
TI  - Absolute phase map recovery of two fringe patterns with flexible selection of
      fringe wavelengths.
AB  - A novel approach is proposed to unwrap the phase maps of two fringe patterns in
      fringe pattern projection-based profilometry. In contrast to existing techniques,
      where spatial frequencies (i.e., the number of fringes on a pattern) of the two
      fringe patterns must be integers and coprime, the proposed method is applicable
      for any two fringe patterns with different fringe wavelengths (i.e., the number
      of pixels in a fringe) and thus provides more flexibility in the use of fringe
      patterns. Moreover, compared to the existing techniques, the proposed method is
      simpler in its implementation and has better antierror capability. Theoretical
      analysis and experiment results are presented to confirm the effectiveness of the
      proposed method. 

PMID- 24663456
TI  - Rapid fabrication of on-demand high-resolution optical masks with a CD-DVD pickup
      unit.
AB  - A low-cost, direct fabrication technique with a micrometer range resolution has
      been implemented for rapid prototyping of optical masks for photolithography and
      structured light and diffraction optics applications. Using a setup based on the
      optical unit of a compact disc-digital versatile disc burner, a low-energy
      infrared laser beam was focused on a thin polymeric layer with embedded absorbing
      carbon nanopowder coated on a transparent glass substrate. This allowed for the
      generation of a custom-made transparent pattern in a computer numerical control
      fashion. In addition to its great simplicity and repeatability, the method also
      enables grayscale contrasts for each pixel individually, and fabricated masks
      proved to resist high intensities. 

PMID- 24663457
TI  - Blue moons and Martian sunsets.
AB  - The familiar yellow or orange disks of the moon and sun, especially when they are
      low in the sky, and brilliant red sunsets are a result of the selective
      extinction (scattering plus absorption) of blue light by atmospheric gas
      molecules and small aerosols, a phenomenon explainable using the Rayleigh
      scattering approximation. On rare occasions, dust or smoke aerosols can cause the
      extinction of red light to exceed that for blue, resulting in the disks of the
      sun and moon to appear as blue. Unlike Earth, the atmosphere of Mars is dominated
      by micron-size dust aerosols, and the sky during sunset takes on a bluish glow.
      Here we investigate the role of dust aerosols in the blue Martian sunsets and the
      occasional blue moons and suns on Earth. We use the Mie theory and the Debye
      series to calculate the wavelength-dependent optical properties of dust aerosols
      most commonly found on Mars. Our findings show that while wavelength selective
      extinction can cause the sun's disk to appear blue, the color of the glow
      surrounding the sun as observed from Mars is due to the dominance of near-forward
      scattering of blue light by dust particles and cannot be explained by a simple,
      Rayleigh-like selective extinction explanation. 

PMID- 24663458
TI  - Spin-coating process evolution and reproducibility for power-law fluids.
AB  - A distinct development of an exact analytical solution for power-law fluids
      during the spin-coating process is presented for temporal and spatial thickness
      evolution, after steady state conditions are attained. This solution leads to the
      definition of a characteristic time, related to the memory of the initial
      thickness profile. Previously obtained experimental data, for several rotation
      speeds and carboxymetilcellulose concentrations in water, are quantitatively
      analyzed through the evaluation of their characteristic times and compared with
      theoretical predictions, thus allowing better understanding of thickness profile
      evolution and of process reproducibility. 

PMID- 24663459
TI  - Terahertz wave generation by nanoconfinement of light.
AB  - This paper presents a novel nanosource of continuous terahertz (THz) wave
      radiation based on difference frequency generation (DFG). Both the optical and
      THz waves are confined in a nanoscale plasmonic waveguide. The results of
      theoretical investigations indicate that the appropriate geometry of the
      plasmonic waveguide has a relatively long optical and THz propagation distance
      (on the order of several tens of wavelengths). Phase matching is obtained using
      the dispersive properties of the waveguide for generating 0.8 THz at the central
      optical wavelength of 1.52 MUm. Our numerical calculation shows that the
      conversion efficiency in this waveguide structure can be achieved up to 5 times
      as large as the micron scale dielectric waveguides and almost 10 times as large
      as the metallic micron scale waveguides.

PMID- 24663460
TI  - Implementation of blind source separation for optical fiber sensing.
AB  - Blind source separation (BSS) is implemented for optical fiber sensing systems,
      such as the fiber Bragg grating (FBG) sensing system and the single-mode
      multimode-single-mode fiber (SMS) sensing system. The FastICA, a kind of
      multichannel BSS algorithm, is used to get the strain and the temperature with
      two FBGs. For the SMS sensing, a single-channel blind source separation (SCBSS)
      algorithm is employed to simultaneously measure the vibration and the temperature
      variation with only one SMS sensor. The errors of both the FBG and the SMS
      optical fiber sensing system are very small with the BSS algorithm. The
      implementation of BSS for the optical fiber sensing makes the multiparameter
      measurements more easily with low cost and high accuracy and can also be applied
      for signal de-noising field. 

PMID- 24663461
TI  - Estimation method of point spread function based on Kalman filter for accurately
      evaluating real optical properties of photonic crystal fibers.
AB  - The evaluation accuracy of real optical properties of photonic crystal fibers
      (PCFs) is determined by the accurate extraction of air hole edges from microscope
      images of cross sections of practical PCFs. A novel estimation method of point
      spread function (PSF) based on Kalman filter is presented to rebuild the
      micrograph image of the PCF cross-section and thus evaluate real optical
      properties for practical PCFs. Through tests on both artificially degraded images
      and microscope images of cross sections of practical PCFs, we prove that the
      proposed method can achieve more accurate PSF estimation and lower PSF variance
      than the traditional Bayesian estimation method, and thus also reduce the defocus
      effect. With this method, we rebuild the microscope images of two kinds of
      commercial PCFs produced by Crystal Fiber and analyze the real optical properties
      of these PCFs. Numerical results are in accord with the product parameters. 

PMID- 24663462
TI  - Optical image processing for synthetic-aperture imaging ladar based on two
      dimensional Fourier transform.
AB  - A two-dimensional (2D) Fourier transform algorithm for the image reconstruction
      of synthetic-aperture imaging ladar (SAIL) collected data is suggested. This
      algorithm consists of quadratic phase compensation in azimuth direction and 2D
      fast Fourier transform. Based on this algorithm and the parallel 2D Fourier
      transform capability of spherical lens, an optical principle scheme that
      processes the SAIL data is proposed. The basic principle, design equations, and
      necessary analysis are presented. To verify this principle scheme, an
      experimental optical SAIL processor setup is constructed. The imaging results of
      SAIL data obtained by our SAIL demonstrator are presented. The optical processor
      is compact, lightweight, and consumes low power. This optical processor can also
      provide inherent parallel and speed-of-light computing capability, and thus has
      potential applications in on-board and satellite-borne SAIL systems. 

PMID- 24663463
TI  - Design of a high-power, high-brightness Nd:YAG solar laser.
AB  - A simple high-power, high-brightness Nd:YAG solar laser pumping approach is
      presented in this paper. The incoming solar radiation is both collected and
      concentrated by four Fresnel lenses and redirected toward a Nd:YAG laser head by
      four plane-folding mirrors. A fused-silica secondary concentrator is used to
      compress the highly concentrated solar radiation to a laser rod. Optimum pumping
      conditions and laser resonator parameters are found through ZEMAX and LASCAD
      numerical analysis. Solar laser power of 96 W is numerically calculated,
      corresponding to the collection efficiency of 24  W/m2. A record-high solar laser
      beam brightness figure of merit of 9.6 W is numerically achieved.

PMID- 24663464
TI  - Uniform sunlight concentration reflectors for photovoltaic cells.
AB  - Sunlight concentration is essential to reach high temperatures of a working fluid
      in solar-thermal applications and to reduce the cost of photovoltaic (PV)
      electricity generation systems. Commonly, sunlight concentration is realized by
      parabolic or cylindrical reflectors, which do not provide uniform concentration
      on the receiver finite surface. Uniform concentration of sunlight is favored
      especially for the PV conversion applications since it not only enhances the
      conversion efficiency of sunlight but also reduces the thermal variations along
      the receiving PV cell, which can be a performance and life-span limiting factor.
      In this paper a reflector profile that uniformly infiltrates the concentrated
      sunlight into the receiving unit is attempted. The new design accounts for all
      factors that contribute to the nonuniform concentration, like the reflector
      curvature, which spatially reflects the sunlight nonuniformly, and the angular
      dependency of both the reflector reflectivity and the sunlight transmission
      through the PV cell. 

PMID- 24663465
TI  - Hybrid daylight/light-emitting diode illumination system for indoor lighting.
AB  - A hybrid illumination method using both daylight and light-emitting diodes (LEDs)
      for indoor lighting is presented in this study. The daylight can be introduced
      into the indoor space by a panel-integration system. The daylight part and LEDs
      are combined within a specific luminaire that can provide uniform illumination.
      The LEDs can be turned on and dimmed through closed-loop control when the
      daylight illuminance is inadequate. We simulated the illumination and calculated
      the indoor lighting efficiency of our hybrid daylight and LED lighting system,
      and compared this with that of LED and fluorescent lighting systems. Simulation
      results show that the efficiency of the hybrid daylight/LED illumination method
      is better than that of LED and traditional lighting systems, under the same
      lighting conditions and lighting time; the method has hybrid lighting average
      energy savings of T5 66.28%, and that of the LEDs is 41.62%. 

PMID- 24663466
TI  - Alignment of a three-mirror anastigmat using the sine condition test.
AB  - Continuing to develop the sine condition test (SCTest), we show how violations of
      the generalized sine condition can be used to align a three-mirror anastigmat
      (TMA). This paper shows how the linear aberrations measured using the sine
      condition, along with aberrations that have constant field dependence, can be
      used to align a system. We discuss the design of the test hardware needed to
      align a TMA and the procedure for alignment. Using simulation, we then
      investigate the behavior of the alignment SCTest for various levels of mirror
      misalignment, mirror fabrication errors, and misalignment of the test equipment.
      All of these tests show that the alignment SCTest can successfully align an
      optical system. 

PMID- 24663467
TI  - Electromagnetically induced self-imaging in four-level atomic system.
AB  - In this paper, a special gradient-index electromagnetically induced transparency
      medium is induced with a Gaussian control field, which can be realized in a four
      level 87Rb cold atomic cloud. Special directional self-imaging and imaging
      transforming properties are studied in this work. Simulated results show that a
      complex object can be imaged in the cold atoms, as the control field substituted
      with the elliptical Gaussian beam, then the self-imaging is directional, which
      has potental application in encryption.

PMID- 24663468
TI  - Rapid ranging through evaluation of image distortion.
AB  - Distortion is an undesirable aberration found in optical imaging systems,
      necessitating numerical calibration. However, the fact that image distortion
      changes with observation distance can be used for ranging. This study developed a
      rapid, passive-ranging technique, which is simple, incurs low costs, results in
      minimal interference, and requires few parameters. After determining the location
      of reference points, the relationship between the normalized mean distortion of
      images and observation distance is described using two mathematical models, one
      of which is based on distortion theory and the other is derived from the curve
      fitting of the experimental results. Analyzing the instantaneous rate of image
      distortion can also assist in ranging. The proposed technique demonstrates high
      sensitivity at closer observation distances, but loses effectiveness as
      observation distances increase. 

PMID- 24663469
TI  - Small-angle measurement with highly sensitive total-internal-reflection
      heterodyne interferometer.
AB  - In this paper, a high-sensitivity total-internal-reflection (TIR) heterodyne
      interferometer is proposed for measuring small angles. In the proposed
      interferometer, a half-wave plate and two quarter-wave plates that exhibit
      specific optic-axis azimuths are combined to form a phase shifter. When a
      rhomboid prism is placed between the phase shifter and an analyzer that exhibits
      suitable transmission-axis azimuth, it shifts and enhances the phase difference
      of the s- and p-polarization states at double TIR. The enhanced phase difference
      is dependent on the incident angle; thus small angles can be easily and
      accurately measured by estimating the phase difference. The experimental results
      demonstrate the feasibility of this method. Angular resolution and sensitivity
      levels superior to 1.2*10-4 deg (2.1*10-6 rad) and 100 (deg/deg), respectively,
      were attainable in a dynamic range of 0.5 deg.

PMID- 24663471
TI  - Super-resolution fusion of complementary panoramic images based on cross
      selection kernel regression interpolation.
AB  - A complementary catadioptric imaging technique was proposed to solve the problem
      of low and nonuniform resolution in omnidirectional imaging. To enhance this
      research, our paper focuses on how to generate a high-resolution panoramic image
      from the captured omnidirectional image. To avoid the interference between the
      inner and outer images while fusing the two complementary views, a cross
      selection kernel regression method is proposed. First, in view of the
      complementarity of sampling resolution in the tangential and radial directions
      between the inner and the outer images, respectively, the horizontal gradients in
      the expected panoramic image are estimated based on the scattered neighboring
      pixels mapped from the outer, while the vertical gradients are estimated using
      the inner image. Then, the size and shape of the regression kernel are adaptively
      steered based on the local gradients. Furthermore, the neighboring pixels in the
      next interpolation step of kernel regression are also selected based on the
      comparison between the horizontal and vertical gradients. In simulation and real
      image experiments, the proposed method outperforms existing kernel regression
      methods and our previous wavelet-based fusion method in terms of both visual
      quality and objective evaluation. 

PMID- 24663470
TI  - Dispersion-free continuum two-dimensional electronic spectrometer.
AB  - Electronic dynamics span broad energy scales with ultrafast time constants in the
      condensed phase. Two-dimensional (2D) electronic spectroscopy permits the study
      of these dynamics with simultaneous resolution in both frequency and time. In
      practice, this technique is sensitive to changes in nonlinear dispersion in the
      laser pulses as time delays are varied during the experiment. We have developed a
      2D spectrometer that uses broadband continuum generated in argon as the light
      source. Using this visible light in phase-sensitive optical experiments presents
      new challenges in implementation. We demonstrate all-reflective interferometric
      delays using angled stages. Upon selecting an ~180  nm window of the available
      bandwidth at ~10  fs compression, we probe the nonlinear response of broadly
      absorbing CdSe quantum dots and electronic transitions of Chlorophyll a.

PMID- 24663472
TI  - Measurement of higher order chromatic dispersion in a photonic bandgap fiber:
      comparative study of spectral interferometric methods.
AB  - Chromatic dispersion of a 37 cm long, solid-core photonic bandgap (PBG) fiber was
      studied in the wavelength range of 740-840 nm with spectral interferometry
      employing a Mach-Zehnder interferometer and a high resolution spectrometer. The
      interferometer was illuminated by a Ti:sapphire laser providing 20 fs pulses. A
      comparative study has been carried out to find the most accurate spectral phase
      retrieval method that is suitable for measuring higher order chromatic
      dispersion. The stationary phase point, the minima-maxima, the cosine function
      fit, the Fourier transform, and the windowed Fourier transform methods were
      tested. It was shown that out of these five techniques, the Fourier-transform
      method provided the dispersion coefficients with the highest accuracy, and it
      could also detect rapid phase changes in the vicinity of leaking mode frequencies
      within the transmission band of the PBG fiber.

PMID- 24663473
TI  - Quantum cascade laser absorption sensor for carbon monoxide in high-pressure
      gases using wavelength modulation spectroscopy.
AB  - A tunable quantum cascade laser sensor, based on wavelength modulation absorption
      spectroscopy near 4.8 MUm, was developed to measure CO concentration in harsh,
      high-pressure combustion gases. The sensor employs a normalized second harmonic
      detection technique (WMS-2f/1f) at a modulation frequency of 50 kHz. Wavelength
      selection at 2059.91  cm-1 targets the P(20) transition within the fundamental
      vibrational band of CO, chosen for absorption strength and relative isolation
      from infrared water and carbon dioxide absorption. The CO spectral model is
      defined by the Voigt line-shape function, and key line-strength and line
      broadening spectroscopic parameters were taken from the literature or measured.
      Sensitivity analysis identified the CO-N2 collisional broadening coefficient as
      most critical for uncertainty mitigation in hydrocarbon/air combustion exhaust
      measurements, and this parameter was experimentally derived over a range of
      combustion temperatures (1100-2600 K) produced in a shock tube. Accuracy of the
      wavelength-modulation-spectroscopy-based sensor, using the refined spectral
      model, was validated at pressures greater than 40 atm in nonreactive shock-heated
      gas mixtures. The laser was then free-space coupled to an indium-fluoride single
      mode fiber for remote light delivery. The fiber-coupled sensor was demonstrated
      on an ethylene/air pulse detonation combustor, providing time-resolved (~20 
      kHz), in situ measurements of CO concentration in a harsh flow field.

PMID- 24663475
TI  - Hollow hybrid plasmonic waveguide for nanoscale optical confinement with long
      range propagation.
AB  - A novel (to our knowledge) hybrid plasmonic (HP) hollow waveguide is proposed for
      nanoscale optical confinement. The light is guided, with improved propagation
      characteristics, in an air slice sandwiched between metal and silicon. The
      optical mode in silicon is dragged toward the metal-dielectric (air) interface to
      make it a HP mode by optimizing the waveguide dimensions. In comparison to the
      hybrid mode confined in the dielectrics, the air-confined hybrid mode exhibits a
      smaller effective mode area A(m)=0.0685/MUm2 and longer propagation distance
      L(p)=142  MUm with a low modal propagation loss of 0.03  dB/MUm at optimized
      values of the width and height of the air slice.

PMID- 24663474
TI  - Dynamic modulation transfer function of a retina-like sensor.
AB  - In this paper, we propose a method to deduce the dynamic modulation transfer
      function (DMTF) of a space-variant sampling retina-like sensor and demonstrate
      its utilization in the forward motion imaging process. With the analysis of
      sampling and the motion imaging property of the sensor, DMTF has been derived.
      Next, the performance of DMTF between a retina-like sensor and a rectilinear
      sensor is compared, and the results show that the degradation of DMTF in forward
      motion is less than that of a rectilinear sensor. Then, the output images are
      obtained through simulation based on DMTF, and they are compared with that
      obtained from a CMOS camera with the same forward motion conditions. The Pearson
      correlation coefficients between the two kinds of images are all larger than
      0.85. Thus, the effectiveness of DMTF is shown. 

PMID- 24663476
TI  - Amplitude-only, passive, broadband, optical spatial cloaking of very large
      objects.
AB  - We demonstrate three amplitude cloaks that can hide very large spatial objects
      over the entire visible spectrum using only passive, off-the-shelf optics. The
      cloaked region for all of the devices exceeds 106 mm3, with the largest exceeding
      108 mm3. Although unidirectional, these cloaks can hide the cloaked object, even
      if the object is transversely illuminated or self-illuminated. Due to the small
      usable solid angle, but simple scaling, these cloaks may be of value in hiding
      small field-of-view objects such as mid- to high-earth orbit satellites from
      earth-based observation. Active phase front manipulation can also make these
      cloaks invisible to some forms of image homodyning.

PMID- 24663477
TI  - Amplification characteristics of a cryogenic Yb3+:YAG total-reflection active
      mirror laser.
AB  - We have studied the amplification characteristics of a cryogenically cooled
      Yb3+:YAG total-reflection active-mirror (TRAM) ceramic laser including wavefront
      distortion, birefringence loss, small signal gain (SSG), and temperature rise for
      developing high-performance master oscillator power amplifier (MOPA) systems. A
      0.6 mm thick Yb3+:YAG ceramic sample was used, and maximum pump intensity ~10 
      kW/cm2 was reached. The transmitted wavefront was measured by using a Shack
      Hartmann wavefront sensor, and we evaluated the thermal lens focal length and
      Strehl ratio for different pump conditions. We have also observed a butterfly
      like leakage profile of thermally induced birefringence loss at the maximum pump
      intensity. From SSG measurements, we obtained moderate laser gain of G=3 for one
      bounce with a near aberration-free wavefront. Gain calculations, which included
      also temperature dependence of the emission cross section and reabsorption of
      Yb3+:YAG, were in good agreement with the experiments. These experimental results
      will be useful as benchmark data for numerical simulations of temperature
      distribution in TRAM and for designing multikilowatt-class high-performance MOPA
      systems.

PMID- 24663478
TI  - Quasi-achromatic Fresnel zone lens with ring focus.
AB  - The phase of a standard Fresnel zone lens (FZL) is periodically modulated in the
      radial direction using the phase of a binary fraxicon. The resulting element (rf
      FZL) focuses light into a ring. The ring is found to be quasi-achromatic, in that
      the diameter is wavelength independent but its location is not. The binary rf-FZL
      is fabricated using electron beam direct writing. Experimental results confirm
      the generation of a wavelength-independent ring pattern at the focus of the rf
      FZL. An efficiency of 24% was obtained. The variation in radius of ring pattern
      was reduced from 61 MUm to less than 10 nm for a corresponding wavelength
      variation from 532 to 633 nm.

PMID- 24663479
TI  - Impact of spontaneous hepatocellular carcinoma rupture on recurrence pattern and
      long-term surgical outcomes after partial hepatectomy.
AB  - BACKGROUND: The clinical significance of spontaneous hepatocellular carcinoma
      (HCC) rupture association with recurrence pattern and long-term surgical outcomes
      remains under debate. We investigated the impact of spontaneous HCC rupture on
      recurrence pattern and long-term surgical outcomes after partial hepatectomy.
      METHODS: From 2000 to 2012, 119 patients with diagnosed ruptured HCC were
      reviewed. To compare outcomes between staged hepatectomy in spontaneously
      ruptured HCC and hepatectomy in non-ruptured HCC, we performed propensity score
      matching to adjust for significant differences in patient characteristics.
      Overall survival, disease-free survival, and recurrence pattern were compared
      between the matched groups. RESULTS: Forty-four patients with newly diagnosed
      ruptured HCC and Child A class were initially treated with transcatheter arterial
      embolization for hemostasis. Three patients underwent emergency laparotomy, 18
      underwent staged hepatectomy, and 23 received transarterial chemoembolization
      (TACE) alone after transcatheter arterial embolization. Among the 23 patients
      treated with TACE alone, 10 had resectable tumors. The staged hepatectomy group
      shows significantly higher overall survival with TACE alone than the resectable
      tumor group (P < 0.001). After propensity score-matching, overall survival,
      disease-free survival, and recurrence pattern were not significantly different
      between the ruptured HCC with staged hepatectomy group and the non-ruptured HCC
      with hepatectomy group. Peritoneal recurrence rates were similar at 14.3% versus
      10.0%, respectively (P = 0.632). CONCLUSIONS: Patients with spontaneously
      ruptured HCC with staged hepatectomy show comparable long-term survival and
      recurrence pattern as patients with non-ruptured HCC having similar tumor
      characteristics and liver functional status. Thus, spontaneous HCC rupture may
      not increase peritoneal recurrence and decrease long-term survival after partial
      hepatectomy.

PMID- 24663480
TI  - Sutureless onlay omental patch for the laparoscopic repair of perforated peptic
      ulcers.
AB  - BACKGROUND: Because the feasibility and safety of laparoscopic approaches for the
      treatment of perforated peptic ulcer (PPU) have been fully recognized,
      laparoscopic repair of PPU (LPPU) has become a widely accepted procedure.
      Following closure of a PPU, the rationale to add an omental patch is based on the
      assumptions that a patch may decrease the possibility of leakage and make the
      closure more secure. However, one of the often mentioned disadvantages of LPPU is
      that it requires a significantly longer operating time. The purpose of the
      present study was to evaluate the efficacy of LPPU with a sutureless onlay
      omental patch. METHODS: Over 60 months, 43 patients underwent LPPU with
      sutureless onlay omental patch, and another 64 patients underwent LPPU with
      sutured omental patch. Patient demographics, operation parameters, and surgical
      outcomes were analyzed retrospectively. RESULTS: All patients in both groups
      survived to the end of the study. There were no leaks in either group. The
      operating time and length of stay in the sutureless onlay omental patch group
      were significantly shorter than in the sutured omental patch group. CONCLUSIONS:
      A sutureless onlay omental patch is as safe and effective as a sutured omental
      patch for the laparoscopic repair of PPU.

PMID- 24663481
TI  - Prevention of incisional hernia in midline laparotomy with an onlay mesh: a
      randomized clinical trial.
AB  - OBJECTIVE: Our objective was to evaluate the prevention of incisional hernia (IH)
      during the postoperative period of a midline laparotomy during elective surgery.
      MATERIAL AND METHODS: A controlled, prospective, randomized, and blind study was
      carried out. The patients in group A (mesh) were fitted with a polypropylene
      mesh, to reinforce the standard abdominal wall closure. The patients in group B
      (non-mesh) underwent a standard abdominal wall closure and were not fitted with
      the mesh. RESULTS: In group A, 2/80 his were diagnosed, whereas in group B the
      number was 30/80. The Kaplan-Meier survival curves show that the likelihood of IH
      at 12 months is 1.5 % in group A compared with 35.9 % in group B (p < 0.0001),
      which means that the differences are statistically significant. CONCLUSION:
      Fitting a prophylactic supra-aponeurotic mesh prevents IH independently of other
      factors.

PMID- 24663482
TI  - Intrahepatic lymphatic invasion but not vascular invasion is a major prognostic
      factor after resection of colorectal cancer liver metastases.
AB  - BACKGROUND: Despite advances in diagnosis and surgical strategies, up to 70% of
      patients will develop recurrence of the disease after resection of colorectal
      cancer liver metastases (CRCLM). The purpose of our study was to determine the
      frequency of four different mechanisms of intrahepatic dissemination, and to
      evaluate the impact of each mechanism on patient outcomes. METHODS: The medical
      records of 118 patients who underwent a first resection of CRCLM during the
      period between 2000 and 2010 were reviewed. Clinicopathologic variables and
      outcome parameters were examined. Resected specimens were submitted to routine
      histological evaluation, and immunohistochemical staining with D2-40 (lymphatic
      vessels), CD34 (blood vessels), CK-7 (biliary epithelium), and CK-20 (CRC cells).
      RESULTS: The mean follow-up after resection was 38 months. Tumor recurrence was
      observed in 76 patients, with a median interval of 13 months after resection.
      Overall survival and disease-free survival (DFS) rates after hepatectomy were 62
      and 56%, and 26 and 24% at 3 and 5 years, respectively. Intrahepatic microscopic
      invasion included portal venous in 49 patients, sinusoidal in 43 patients,
      biliary in 20 patients, and lymphatic in 33 patients. Intra-hepatic lymphatic
      invasion was the only mechanism of dissemination independently associated with
      the risk of hepatic recurrence (odds ratio 2.75) and shorter DFS (p = 0.006).
      CONCLUSION: Intrahepatic lymphatic invasion is a significant prognostic factor.
      Other mechanisms of invasion, although frequently observed, are not related to
      recurrence or survival, suggesting that the lymphatic system is the main route
      for dissemination of CRCLM. Furthermore, immunohistochemical detection of
      intrahepatic lymphatic invasion might be of value in clinical practice.

PMID- 24663483
TI  - A cost analysis of somatostatin use in the prevention of pancreatic fistula after
      pancreatectomy.
AB  - BACKGROUND: Studies have shown that somatostatin reduces the occurrence of
      postoperative pancreatic fistula. However, no study to date has analyzed the cost
      effectiveness of this treatment. The purpose of this study was to analyze the
      cost effectiveness of prophylactic somatostatin use with respect to
      pancreatectomy. METHODS: Review of prospectively collected 2002 patient hepato
      pancreatico-biliary database from January 2007 to May 2012. Patients received
      somatostatin prophylactically at the discretion of their surgeon. Data were
      analyzed using univariate analysis to determine if somatostatin had an effect on
      imaging costs, lab costs, "other" costs, PT/OT costs, surgery costs, room and
      board costs, and total hospital costs. RESULTS: A total of 179 patients underwent
      pancreatectomy at a single teaching institution. Median total hospital costs were
      90,673.50 (59,979-743,667) for patients who developed a postoperative pancreatic
      fistula versus 86,563 (39,190-463,601) for those who did not (p = 0.004). Median
      total hospital costs were 89,369 (39,190-743,667) for patients who were
      administered somatostatin versus 85,291 (40,092-463,601) for patients who did not
      (p = 0.821). CONCLUSIONS: Pancreatic fistulas significantly increase hospital
      costs, and somatostatin has been shown to decrease the rate of pancreatic fistula
      formation. Somatostatin has no significant effect on hospital costs.

PMID- 24663484
TI  - The post-2015 development agenda: the role of surgical care in improving health.

PMID- 24663485
TI  - Primary hyperparathyroidism: an analysis of failure of parathyroidectomy.

PMID- 24663486
TI  - Distinct actions of akt1 on skeletal architecture and function.
AB  - Skeletal integrity is dependent on the coordinated actions of bone-forming
      osteoblasts and bone-resorbing osteoclasts, which recognize and respond to
      multiple environmental inputs. Here we have studied the roles in bone development
      and growth of Akt1 and Akt2, two closely related signaling proteins, by
      evaluating mice lacking either of these enzymes. Global deficiency of Akt1 but
      not Akt2 caused a reduction in whole body and femoral bone mineral density, in
      femoral cortical thickness and volume, and in trabecular thickness in both males
      and females when measured at 20-weeks of age, which was reflected in diminished
      femoral resistance to fracture. Haplo-deficiency of Akt1 in male mice also
      decreased femoral cortical and trabecular skeletal parameters, and reduced bone
      strength. Cell-based studies showed that genetic Akt1 deficiency diminished the
      rate of proliferation of osteoblast progenitors and impaired osteoclast
      differentiation in primary culture but that loss of Akt2 did not. Our results
      demonstrate differential effects of Akt1 and Akt2 on skeletal maturation and
      architecture through actions on both osteoblast and osteoclast precursors. 

PMID- 24663487
TI  - Coinfection of human herpesviruses 6A (HHV-6A) and HHV-6B as demonstrated by
      novel digital droplet PCR assay.
AB  - The human herpesviruses HHV-6A and HHV-6B have been associated with various
      neurologic disorders partly due to the detection of elevated viral DNA levels in
      patients compared to controls. However the reported frequency of these viruses
      varies widely, likely reflecting differences in PCR methodologies used for
      detection. Digital droplet PCR (ddPCR) is a third generation PCR technology that
      enables the absolute quantification of target DNA molecules. Mounting evidence of
      the biological differences between HHV-6A and HHV-6B has led to their recent
      reclassification as separate species. As it is now especially relevant to
      investigate each virus, our objectives were to first design a multiplex HHV-6A
      and HHV-6B ddPCR assay and then to investigate the incidence of HHV-6A and HHV-6B
      coinfection in samples from healthy donors and patients with MS, a disease in
      which HHV-6 is thought to play a role. In our assessment of healthy donors, we
      observed a heretofore-underappreciated high frequency of coinfection in PBMC and
      serum, and found that our assay precisely detects both HHV-6A and HHV-6B
      chromosomally integrated virus, which has important implications in clinical
      settings. Interestingly, upon comparing the saliva from MS patients and healthy
      donors, we detected a significantly elevated frequency of coinfection in MS
      saliva; increased detection of HHV-6A in MS patients is consistent with other
      studies suggesting that this viral species (thought to be more neurotropic than
      HHV-6B) is more prevalent among MS patients compared to healthy donors. As the
      biology and disease associations between these two viral species differ,
      identifying and quantifying both species of HHV-6 may provide clinically relevant
      information, as well as enhance our understanding of the roles of each in health
      and disease. 

PMID- 24663489
TI  - Effects of lake warming on behavioural thermoregulatory tactics in a cold-water
      stenothermic fish.
AB  - Despite some evidence of within-population phenotypic variation in fish thermal
      behaviour, the occurrence of alternative tactics of this behaviour is rarely
      explicitly considered when studying natural populations. Brook charr provide an
      example of within-population variability in behavioural thermoregulation as
      revealed by a recent study on a lacustrine population of this species. The
      objectives of the present study were (i) to determine the influence of natural
      variability in the lake's thermal profiles on the expression of thermoregulatory
      tactics, and (ii) to determine the vertical and horizontal movements of
      individuals at different periods of the day to better understand the spatio
      temporal behaviour associated with each thermoregulatory tactic. During summer
      2010, 30 adult brook charr were equipped with thermo-sensitive radio transmitters
      to monitor their selected temperatures and daily movements. These individuals
      exhibited the same four behavioural thermoregulatory tactics observed in 2003 and
      2005, but the expression of two of these was weaker in 2010. This result was
      associated with lake warming, which constrained the expression of two
      thermoregulatory tactics: brook charr significantly decreased their selected
      temperatures and daily movements when the mean daily epilimnion temperature was
      above 22.4 degrees C. This study shows for the first time that the expression of
      behavioural thermoregulatory tactics is related to the lake's thermal regime and
      that the tactics are plastic through time. 

PMID- 24663490
TI  - Early Detection of Human Epileptic Seizures Based on Intracortical Local Field
      Potentials.
AB  - The unpredictability of re-occurring seizures dramatically impacts the quality of
      life and autonomy of people with epilepsy. Reliable early seizure detection could
      open new therapeutic possibilities and thus substantially improve quality of life
      and autonomy. Though many seizure detection studies have shown the potential of
      scalp electroencephalogram (EEG) and intracranial EEG (iEEG) signals, reliable
      early detection of human seizures remains elusive in practice. Here, we examined
      the use of intracortical local field potentials (LFPs) recorded from 4*4-mm2 96
      microelectrode arrays (MEA) for early detection of human epileptic seizures. We
      adopted a framework consisting of (1) sampling of intracortical LFPs; (2)
      denoising of LFPs with the Kalman filter; (3) spectral power estimation in
      specific frequency bands using 1-sec moving time windows; (4) extraction of
      statistical features, such as the mean, variance, and Fano factor (calculated
      across channels) of the power in each frequency band; and (5) cost-sensitive
      support vector machine (SVM) classification of ictal and interictal samples. We
      tested the framework in one-participant dataset, including 4 seizures and
      corresponding interictal recordings preceding each seizure. The participant was a
      52-year-old woman suffering from complex partial seizures. LFPs were recorded
      from an MEA implanted in the participant's left middle temporal gyrus. In this
      participant, spectral power in 0.3-10 Hz, 20-55 Hz, and 125-250 Hz changed
      significantly between ictal and interictal epochs. The examined seizure detection
      framework provided an event-wise sensitivity of 100% (4/4) and only one 20-sec
      long false positive event in interictal recordings (likely an undetected
      subclinical event under further visual inspection), and a detection latency of
      4.35 +/- 2.21 sec (mean +/- std) with respect to iEEG-identified seizure onsets.
      These preliminary results indicate that intracortical MEA recordings may provide
      key signals to quickly and reliably detect human seizures.

PMID- 24663488
TI  - Admixture fine-mapping in African Americans implicates XAF1 as a possible
      sarcoidosis risk gene.
AB  - Sarcoidosis is a complex, multi-organ granulomatous disease with a likely genetic
      component. West African ancestry confers a higher risk for sarcoidosis than
      European ancestry. Admixture mapping provides the most direct method to locate
      genes that underlie such ethnic variation in disease risk. We sought to identify
      genetic risk variants within four previously-identified ancestry-associated
      regions-6p24.3-p12.1, 17p13.3-13.1, 2p13.3-q12.1, and 6q23.3-q25.2-in a sample of
      2,727 African Americans. We used logistic regression fit by generalized
      estimating equations and the MIX score statistic to determine which variants
      within ancestry-associated regions were associated with risk and responsible for
      the admixture signal. Fine mapping was performed by imputation, based on a
      previous genome-wide association study; significant variants were validated by
      direct genotyping. Within the 6p24.3-p12.1 locus, the most significant ancestry
      adjusted SNP was rs74318745 (p = 9.4*10-11), an intronic SNP within the HLA-DRA
      gene that did not solely explain the admixture signal, indicating the presence of
      more than a single risk variant within this well-established sarcoidosis risk
      region. The locus on chromosome 17p13.3-13.1 revealed a novel sarcoidosis risk
      SNP, rs6502976 (p = 9.5*10-6), within intron 5 of the gene X-linked Inhibitor of
      Apoptosis Associated Factor 1 (XAF1) that accounted for the majority of the
      admixture linkage signal. Immunohistochemical expression studies demonstrated
      lack of expression of XAF1 and a corresponding high level of expression of its
      downstream target, X-linked Inhibitor of Apoptosis (XIAP) in sarcoidosis
      granulomas. In conclusion, ancestry and association fine mapping revealed a novel
      sarcoidosis susceptibility gene, XAF1, which has not been identified by previous
      genome-wide association studies. Based on the known biology of the XIAP/XAF1
      apoptosis pathway and the differential expression patterns of XAF1 and XIAP in
      sarcoidosis granulomas, we suggest that this pathway may play a role in the
      maintenance of sarcoidosis granulomas. 

PMID- 24663491
TI  - Accuracy evaluation of the unified P-value from combining correlated P-values.
AB  - Meta-analysis methods that combine P-values into a single unified P-value are
      frequently employed to improve confidence in hypothesis testing. An assumption
      made by most meta-analysis methods is that the P-values to be combined are
      independent, which may not always be true. To investigate the accuracy of the
      unified P-value from combining correlated P-values, we have evaluated a family of
      statistical methods that combine: independent, weighted independent, correlated,
      and weighted correlated P-values. Statistical accuracy evaluation by combining
      simulated correlated P-values showed that correlation among P-values can have a
      significant effect on the accuracy of the combined P-value obtained. Among the
      statistical methods evaluated those that weight P-values compute more accurate
      combined P-values than those that do not. Also, statistical methods that utilize
      the correlation information have the best performance, producing significantly
      more accurate combined P-values. In our study we have demonstrated that
      statistical methods that combine P-values based on the assumption of independence
      can produce inaccurate P-values when combining correlated P-values, even when the
      P-values are only weakly correlated. Therefore, to prevent from drawing false
      conclusions during hypothesis testing, our study advises caution be used when
      interpreting the P-value obtained from combining P-values of unknown correlation.
      However, when the correlation information is available, the weighting-capable
      statistical method, first introduced by Brown and recently modified by Hou, seems
      to perform the best amongst the methods investigated.

PMID- 24663493
TI  - Iron acquisition and regulation systems in Streptococcus species.
AB  - Gram-positive Streptococcus species are responsible for millions of cases of
      meningitis, bacterial pneumonia, endocarditis, erysipelas and necrotizing
      fasciitis. Iron is essential for the growth and survival of Streptococcus in the
      host environment. Streptococcus species have developed various mechanisms to
      uptake iron from an environment with limited available iron. Streptococcus can
      directly extract iron from host iron-containing proteins such as ferritin,
      transferrin, lactoferrin and hemoproteins, or indirectly by relying on the
      employment of specialized secreted hemophores (heme chelators) and small
      siderophore molecules (high affinity ferric chelators). This review presents the
      most recent discoveries in the iron acquisition system of Streptococcus species -
      the transporters as well as the regulators. 

PMID- 24663492
TI  - High-lard and high-fish-oil diets differ in their effects on function and dynamic
      behaviour of rat hepatic mitochondria.
AB  - BACKGROUND: Mitochondria are dynamic organelles that frequently undergo fission
      and fusion processes, and imbalances in these processes may be involved in
      obesity and insulin resistance. AIMS: The present work had the following aims:
      (a) to evaluate whether the mitochondrial dysfunction present in the hepatic
      steatosis induced by a high-fat diet is associated with changes in mitochondrial
      dynamics and morphology; (b) to evaluate whether effects on the above parameters
      differ between high-lard and high-fish-oil diets, as it has been suggested that
      fish oil may have anti-obesity and anti-steatotic effects by stimulating fatty
      acids utilisation. METHODS: The development of hepatic steatosis and insulin
      resistance was monitored in rats fed a high-lard or high-fish-oil diet.
      Immunohistochemical and electronic microscopic observations were performed on
      liver sections. In isolated liver mitochondria, assessments of fatty acids
      oxidation rate, proton conductance and oxidative stress (by measuring H2O2
      release and aconitase activity) were performed. Western blot and
      immunohistochemical analyses were performed to evaluate the presence of proteins
      involved in mitochondrial dynamics (i.e., fusion and fission processes). To
      investigate the fusion process, mitofusin 2 and autosomal dominant optic atrophy
      1 (OPA1) were analysed. To investigate the fission process, the presence of
      dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1) was assessed.
      RESULTS: High-lard feeding elicited greater hepatic lipid accumulation, insulin
      resistance with associated mitochondrial dysfunction, greater oxidative stress
      and a shift towards mitochondrial fission processes (versus high-fish-oil
      feeding, which had an anti-steatotic effect associated with increased
      mitochondrial fusion processes). CONCLUSIONS: Different types of high-fat diets
      differ in their effect on mitochondrial function and dynamic behaviour, leading
      to different cellular adaptations to over-feeding.

PMID- 24663495
TI  - Automation of o-dianisidine assay for ceruloplasmin activity analyses: usefulness
      of investigation in Wilson's disease and in hepatic encephalopathy.
AB  - Ceruloplasmin (Cp) is a serum ferroxidase that plays an essential role in iron
      metabolism. It is routinely tested by immunoturbidimetric assays that quantify
      the concentration of the protein both in its active and inactive forms. Cp
      activity is generally analyzed manually; the process is time-consuming, has a
      limited repeatability, and is not suitable for a clinical setting. To overcome
      these inconveniences, we have set the automation of the o-dianisidine Cp activity
      assay on a Cobas Mira Plus apparatus. The automation was rapid and repeatable,
      and the data were provided in terms of IU/L. The assay was adapted for human sera
      and showed a good precision [coefficient of variation (CV) 3.7 %] and low limit
      of detection (LoD 11.58 IU/L). The simultaneous analysis of Cp concentration and
      activity in the same run allowed us to calculate the Cp-specific activity that
      provides a better index of the overall Cp status. To test the usefulness of this
      automation, we tested this assay on 104 healthy volunteers and 36 patients with
      Wilson's disease, hepatic encephalopathy, and chronic liver disease. Cp activity
      and specific activity distinguished better patients between groups with respect
      to Cp concentration alone, and providing support for the clinical investigation
      of neurological diseases in which liver failure is one of the clinical hallmarks.

PMID- 24663494
TI  - A systematic review of fetal genes as biomarkers of cardiac hypertrophy in rodent
      models of diabetes.
AB  - Pathological cardiac hypertrophy activates a suite of genes called the fetal gene
      program (FGP). Pathological hypertrophy occurs in diabetic cardiomyopathy (DCM);
      therefore, the FGP is widely used as a biomarker of DCM in animal studies.
      However, it is unknown whether the FGP is a consistent marker of hypertrophy in
      rodent models of diabetes. Therefore, we analyzed this relationship in 94
      systematically selected studies. Results showed that diabetes induced with
      cytotoxic glucose analogs such as streptozotocin was associated with decreased
      cardiac weight, but genetic or diet-induced models of diabetes were significantly
      more likely to show cardiac hypertrophy (P<0.05). Animal strain, sex, age, and
      duration of diabetes did not moderate this effect. There were no correlations
      between the heart weight:body weight index and mRNA or protein levels of the
      fetal genes alpha-myosin heavy chain (alpha-MHC) or beta-MHC, sarco/endoplasmic
      reticulum Ca2+-ATPase, atrial natriuretic peptide (ANP), or brain natriuretic
      peptide. The only correlates of non-indexed heart weight were the protein levels
      of alpha-MHC (Spearman's rho = 1, P<0.05) and ANP (rho = -0.73, P<0.05). These
      results indicate that most commonly measured genes in the FGP are confounded by
      diabetogenic methods, and are not associated with cardiac hypertrophy in rodent
      models of diabetes. 

PMID- 24663496
TI  - Botulinum toxin A in functional popliteal entrapment syndrome: a new approach to
      a difficult diagnosis.
AB  - Functional Popliteal Entrapment Syndrome (FPES) is caused by compression of
      neurovascular structures in the popliteal fossa by hypertrophic muscles,
      provoking severe leg pain with exercise. Treatment is limited to myotomy of
      hypertrophic musculature. 8 FPES patients underwent imaging and exercise studies,
      before receiving botulinum toxin A injections (BTX-A) into the gastrocnemius and
      plantaris muscles. 81.3 % of patients reported clinical improvement on follow-up,
      and pathological ankle-brachial indices were normalized. BTX-A injection may
      present a new, safe, effective and non-invasive approach to FPES.

PMID- 24663498
TI  - Collaboration within the M1 aminopeptidase family promotes reproductive success
      in Caenorhabditis elegans.
AB  - Mutations of the puromycin-sensitive aminopeptidase (Psa) orthologs of flies,
      mice, and plants result in meiotic errors and reduced embryonic viability.
      Genetic lesions of the Caenorhabditis elegans ortholog of Psa, pam-1, similarly
      result in dramatic reductions of worm fecundity. The gonads of animals harboring
      mutant pam-1 alleles display expanded populations of pachytene germinal nuclei
      and delayed nucleolar disassembly in the developing oocytes, phenotypes that
      ultimately hinder embryonic viability and overall brood sizes. PAM-1 is a member
      of the M1 aminopeptidase family and shares a high amount of homology with its M1
      paralogs. Comparative analysis of the M1 aminopeptidase family reveals that only
      nine (including PAM-1) of the 17 annotated M1 aminopeptidases are predicted to be
      catalytically active. Interestingly, we demonstrate that three of these active M1
      paralogs have roles independent of PAM-1 in promoting gametogenesis and
      fecundity. Simultaneous inhibition of pam-1 and M1 paralogs produces synergistic
      decreases in overall brood sizes and embryonic viability, exacerbates the
      germinal phenotypes of pachytene extension and delayed nucleolar disassembly, and
      unmasks previously hidden phenotypes. Our data suggests that the interdependent
      functions of multiple M1 aminopeptidases are necessary for reproductive success
      in C. elegans and lend further credence to the redundant composition of an
      evolutionarily conserved enzyme family. 

PMID- 24663499
TI  - In situ growth of a MoSe2/Mo counter electrode for high efficiency dye-sensitized
      solar cells.
AB  - A facile and economical MoSe2/Mo structure was in situ prepared to replace the
      currently preferred expensive Pt and FTO counter electrode (CE) in dye-sensitized
      solar cells. A power conversion efficiency of 8.13% was achieved, which is
      comparable to that with Pt-sputtered FTO electrode (8.06%). 

PMID- 24663501
TI  - DrugPath: a database for academic investigators to match oncology molecular
      targets with drugs in development.
AB  - PURPOSE: Academic laboratories are developing increasingly large amounts of data
      that describe the genomic landscape and gene expression patterns of various types
      of cancers. Such data can potentially identify novel oncology molecular targets
      in cancer types that may not be the primary focus of a drug sponsor's initial
      research for an investigational new drug. Obtaining preclinical data that point
      toward the potential for a given molecularly targeted agent, or a novel
      combination of agents requires knowledge of drugs currently in development in
      both the academic and commercial sectors. METHODS: We have developed the DrugPath
      database ( http://www.drugpath.org ) as a comprehensive, free-of-charge resource
      for academic investigators to identify agents being developed in academics or
      industry that may act against molecular targets of interest. DrugPath data on
      molecular targets overlay the Michigan Molecular Interactions (
      http://mimi.ncibi.org ) gene-gene interaction map to facilitate identification of
      related agents in the same pathway. RESULTS: The database catalogs 2,081 drug
      development programs representing 751 drug sponsors and 722 molecular and genetic
      targets. CONCLUSIONS: DrugPath should assist investigators in identifying and
      obtaining drugs acting on specific molecular targets for biological and
      preclinical therapeutic studies.

PMID- 24663500
TI  - Monocrotophos induces the expression and activity of xenobiotic metabolizing
      enzymes in pre-sensitized cultured human brain cells.
AB  - The expression and metabolic profile of cytochrome P450s (CYPs) is largely
      missing in human brain due to non-availability of brain tissue. We attempted to
      address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG)
      cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the
      cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide
      (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used
      organophosphorous pesticide. Both the cells show significant induction in the
      expression and CYP-specific activity against classical inducers and MCP. The
      induction level of CYPs was comparatively lower in MCP exposed cells than cells
      exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers
      significantly added the MCP induced CYPs expression and activity. The findings
      were concurrent with protein ligand docking studies, which show a significant
      modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and
      AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown
      significantly high docking scores with all the three studied CYP regulators. The
      expression of CYPs in neuronal and glial cells has suggested their possible
      association with the endogenous physiology of the brain. The findings also
      suggest the xenobiotic metabolizing capabilities of these cells against MCP, if
      received a pre-sensitization to trigger the xenobiotic metabolizing machinery.
      MCP induced CYP-specific activity in neuronal cells could help in explaining its
      effect on neurotransmission, as these CYPs are known to involve in the
      synthesis/transport of the neurotransmitters. The induction of CYPs in glial
      cells is also of significance as these cells are thought to be involved in
      protecting the neurons from environmental insults and safeguard them from
      toxicity. The data provide better understanding of the metabolizing capability of
      the human brain cells against xenobiotics. 

PMID- 24663502
TI  - Rate and extent of oxaliplatin absorption after hyperthermic intraperitoneal
      administration in peritoneal carcinomatosis patients.
AB  - PURPOSE: To determine the rate and extent of hyperthermic intraperitoneal
      oxaliplatin (HIO) absorption in peritoneal carcinomatosis patients treated with
      cytoreductive surgery (CRS) and the effect of the isotonic carrier solution on
      HIO absorption parameters. METHODS: Full pharmacokinetic profiles collected in
      peritoneum and plasma from 57 subjects treated with CRS followed by 30 min of HIO
      were pooled with sparse plasma concentrations collected from 50 patients with
      solid tumors treated with intravenous oxaliplatin. Pharmacokinetic data were
      jointly analyzed with nonlinear mixed-effect model (NONMEM VII software). The
      effect of carrier solution (icodextrin 4 % vs. dextrose 5 %) and selected patient
      covariates on oxaliplatin pharmacokinetics was investigated. Model evaluation was
      performed using predictive checks and nonparametric bootstrap. RESULTS: An open
      linear two-compartment disposition model with linear absorption from peritoneum
      to plasma was used to characterize the oxaliplatin pharmacokinetics in peritoneum
      and plasma. No patient-related covariates were associated with oxaliplatin
      pharmacokinetics. The volume of distribution in the peritoneum (V a)
      exponentially decreased due to the carrier solute absorption. The reduction in V
      a was 1.76-fold faster when HIO was administered in dextrose 5 %, relative to
      icodextrin 4 %. For HIO durations of 30 min, the rate of oxaliplatin absorption
      ranges from 0.84 to 0.96 h(-1) for icodextrin 4 % and from 0.86 to 1.09 h(-1) for
      dextrose 5 %. The extent of HIO absorption was 38 %, regardless of the carrier
      solution. CONCLUSIONS: Hyperthermic intraperitoneal oxaliplatin absorption is
      fast and incomplete. The small difference in oxaliplatin exposure between both
      carrier solutions evaluated is not clinically relevant for HIO durations of 30
      min.

PMID- 24663503
TI  - Is there any predictor for clinical outcome in EGFR mutant NSCLC patients treated
      with EGFR TKIs?
AB  - BACKGROUND: Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor
      receptor (EGFR) have demonstrated some dramatic response rate and prolonged
      progression-free survival (PFS) in advanced non-small-cell lung cancer (NSCLC)
      patients with activating EGFR mutation. However, PFS and overall survival (OS)
      among those patients who were treated with EGFR TKIs are inconsistent and
      unpredictable. In this study, we evaluated predictors of clinical outcome in EGFR
      mutant NSCLC patients treated with EGFR TKIs. METHODS: A total of 148 patients
      who had metastatic or recurrent NSCLC with activating EGFR mutation treated with
      either erlotinib or gefitinib as a first-line (n = 10) and a second-line or more
      treatment (n = 138) were retrospectively reviewed. RESULTS: The median follow-up
      duration was 21.9 months (range, 1.1-62.5). The median PFS and OS for a total 148
      patients were 10.6 months (95 % CI 9.0-12.2) and 21.8 months (95 % CI 18.5-25.1),
      respectively. The survival outcomes were similar between the first-line and
      second-line or more line of treatment of EGFR TKIs (P = 0.512 for PFS, P = 0.699
      for OS). Although a high number of metastasis sites (3-6 vs. 1-2) were associated
      with shorter PFS and OS (median PFS 9.9 vs. 11.9 months, P = 0.019; median OS
      16.4 vs. 22.2 months, P = 0.021, respectively) in univariate analysis, but not in
      multivariate analysis. According to the clinical and molecular markers by
      multivariate analysis, there were no significant differences in PFS. When PFS was
      dichotomized by median 11 months for 105 patients treated with EGFR TKIs as
      second-line therapy, no significant differences in any clinical or molecular
      features were found between longer PFS and shorter PFS groups. CONCLUSIONS:
      Despite the inconsistencies in PFS among EGFR mutant patients treated with EGFR
      TKIs, no significant differences of clinical features were noted, thereby
      suggesting a need for more understanding of the heterogeneity of underlying
      biology.

PMID- 24663504
TI  - A phase I study of oral ixabepilone in patients with advanced solid tumors.
AB  - BACKGROUND: Intravenous infusion of ixabepilone is Food and Drug Administration
      approved for treatment of patients with metastatic breast cancer. The aim of this
      study was to establish the maximum tolerated dose (MTD), dose-limiting toxicities
      (DLTs), safety, and pharmacokinetics (PK) of a novel oral formulation of
      ixabepilone in patients with advanced solid tumors. PATIENTS AND METHODS: Forty
      four patients received one of six daily doses of oral ixabepilone (5, 10, 15, 20,
      25, or 30 mg) on days 1-5 of a 21-day cycle. PK parameters were evaluated in
      cycle 1 for all treated patients and in cycle 1 and cycle 2 for patients
      participating in assessments of food and gastric pH effects. RESULTS: The most
      common DLTs (reported in at least one patient) were neutropenia, neutropenic
      fever, diarrhea, ileus, and hypokalemia. The MTD of oral ixabepilone was 25 mg.
      Plasma concentrations of ixabepilone showed high variability; coefficients of
      variation for the area under the curve and the peak plasma concentration ranged
      from 61 to 131 % and from 17 to 172 %, respectively. The mean half-life of
      ixabepilone calculated after day 5 of cycle 1 ranged from 24 to 47 h. Ixabepilone
      exposure was higher when administered with a low-fat meal compared with the
      fasted state, and when administered 2 h after the histamine H2 receptor
      antagonist famotidine. CONCLUSIONS: The MTD of oral ixabepilone when administered
      once daily for five consecutive days every 21 days was 25 mg. Ixabepilone
      exposure was highly variable; therefore, safety and efficacy of this novel oral
      formulation might not be reliably predicted.

PMID- 24663505
TI  - Microfluidic platforms for biomarker analysis.
AB  - Biomarkers have been described as characteristics, most often molecular, that
      provide information about biological states, whether normal, pathological, or
      therapeutically modified. They hold great potential to assist diagnosis and
      prognosis, monitor disease, and assess therapeutic effectiveness. While a few
      biomarkers are routinely utilised clinically, these only reflect a very small
      percentage of all biomarkers discovered. Numerous factors contribute to the slow
      uptake of these new biomarkers, with challenges faced throughout the biomarker
      development pipeline. Microfluidics offers two important opportunities to the
      field of biomarkers: firstly, it can address some of these developmental
      obstacles, and secondly, it can provide the precise and complex platform required
      to bridge the gap between biomarker research and the biomarker-based analytical
      device market. Indeed, adoption of microfluidics has provided a new avenue for
      advancement, promoting clinical utilisation of both biomarkers and their
      analytical platforms. This review will discuss biomarkers and outline
      microfluidic platforms developed for biomarker analysis. 

PMID- 24663507
TI  - Anthony's story.

PMID- 24663506
TI  - Epidemiology of masked and white-coat hypertension: the family-based SKIPOGH
      study.
AB  - OBJECTIVE: We investigated factors associated with masked and white-coat
      hypertension in a Swiss population-based sample. METHODS: The Swiss Kidney
      Project on Genes in Hypertension is a family-based cross-sectional study. Office
      and 24-hour ambulatory blood pressure were measured using validated devices.
      Masked hypertension was defined as office blood pressure<140/90 mmHg and daytime
      ambulatory blood pressure>=135/85 mmHg. White-coat hypertension was defined as
      office blood pressure>=140/90 mmHg and daytime ambulatory blood pressure<135/85
      mmHg. Mixed-effect logistic regression was used to examine the relationship of
      masked and white-coat hypertension with associated factors, while taking familial
      correlations into account. High-normal office blood pressure was defined as
      systolic/diastolic blood pressure within the 130-139/85-89 mmHg range. RESULTS:
      Among the 652 participants included in this analysis, 51% were female. Mean age
      (+/-SD) was 48 (+/-18) years. The proportion of participants with masked and
      white coat hypertension was respectively 15.8% and 2.6%. Masked hypertension was
      associated with age (odds ratio (OR) = 1.02, p = 0.012), high-normal office blood
      pressure (OR = 6.68, p<0.001), and obesity (OR = 3.63, p = 0.001). White-coat
      hypertension was significantly associated with age (OR = 1.07, p<0.001) but not
      with education, family history of hypertension, or physical activity.
      CONCLUSIONS: Our findings suggest that physicians should consider ambulatory
      blood pressure monitoring for older individuals with high-normal office blood
      pressure and/or who are obese.

PMID- 24663509
TI  - Bilayer metallic nanofilms as broadband antireflection coatings in terahertz
      optical systems.
AB  - We present the potential of ultrathin bilayer metallic nanofilms for use as
      broadband antireflection coatings in the terahertz frequency range. The metallic
      layers are modeled using a wave-impedance matching approach. The experimental and
      theoretical results are in good agreement. Further, a novel method using our
      broadband antireflection coatings is proposed to eliminate unwanted reflections
      that interfere with the important reflection from the sample in terahertz
      reflection measurement. The proposed method significantly improves the
      calculation of the optical properties of liquid and biological samples. 

PMID- 24663508
TI  - A distributed fiber vibration sensor utilizing dispersion induced walk-off effect
      in a unidirectional Mach-Zehnder interferometer.
AB  - We propose and experimentally demonstrate a novel ultra-long range and sensitive
      distributed fiber vibration sensor. Only one unidirectional Mach-Zehnder
      interferometer (MZI) is employed in this scheme as the sensing element. In this
      sensor structure, we utilize chromatic dispersion-induced walk-off effect between
      the vibration signals sensed by two distributed feedback (DFB) lasers at
      different wavelengths to locate the vibration position. Vibration signals with
      frequencies up to 9 MHz can be detected and the spatial resolution of 31 m is
      achieved over 320 km of the standard single mode fiber. Monitoring multiple
      vibration sources can also be realized using this scheme.

PMID- 24663510
TI  - Performance improvement of double-sideband signals in radio-over-fiber links
      utilizing pre-distortion method.
AB  - In this paper, we investigate the optimal carrier-to-sideband ratio (CSR) for
      optical double-sideband (DSB) signals in radio-over-fiber (RoF) transmission. A
      pre-distortion method based on spectral shaping is proposed to optimize the
      signal CSR and eliminate the dispersion-induced power fading. A 12 GHz RoF
      transmission over 29 km standard single mode fiber (SSMF) is experimentally
      demonstrated which reveals that pre-distorted DSB has a 4.4 dB improvement over
      the one without pre-distortion, and 1.2 dB sensitivity advantage over single
      sideband (SSB) both with optimal CSR. The pre-distortion method is also applied
      to multi-channel transmission. The multi-channel experiment shows that for all
      channels the dispersion-induced power fading effects can be simultaneously
      mitigated and the pre-distorted DSB signals have ~1 dB sensitivity improvement
      over the SSB signals. 

PMID- 24663511
TI  - 3D holographic printer: fast printing approach.
AB  - This article describes the general operation principles of devices for
      synthesized holographic images such as holographic printers. Special emphasis is
      placed on the printing speed. In addition, various methods to increase the
      printing process are described and compared. 

PMID- 24663512
TI  - The effects of MPE on electro-holographic displays.
AB  - The effects of MPE (maximum permissible exposure) on the characteristics of
      electro-holographic displays are analyzed. The main effect is the reduction in
      the spectral range to be presented by the displays. The range will be reduced
      more as the pixel and hologram sizes of the displays become smaller and larger,
      respectively. The spectral range for the hologram size 0.5m and pixel size 0.8 um
      will be about 50 nm less than that of the visible. In addition to the spectral
      range, the reconstructed image size should not be smaller than the value defined
      by 0.1 times of the diffracted intensity of the image to meet the MPE requirement
      for eye.

PMID- 24663513
TI  - 1x11 few-mode fiber wavelength selective switch using photonic lanterns.
AB  - We demonstrate an 11 port count wavelength selective switch (WSS) supporting
      spatial superchannels of three spatial modes, based on the combination of
      photonic lanterns and a high-port count single-mode WSS. 

PMID- 24663514
TI  - Polarization anisotropic transmission through metallic Sierpinski-Carpet aperture
      array.
AB  - Extraordinary optical transmission through rectangular Sierpinski -Carpet
      aperture array on an Ag film has been observed. Attributed to the fractal
      featured rectangle array, it exhibits polarization dependence and dual-band
      transmission simultaneously. In addition, the incident angle invariance
      transmission displays within a certain angle range, which is quite different from
      ordinary rectangles. This report provides a way to achieve the polarization
      manipulated multi-band transmission in infrared region. 

PMID- 24663515
TI  - Anisotropy of laser emission in monoclinic, disordered crystal Nd:LYSO.
AB  - Multi-wavelength emissions have been demonstrated in many disordered laser
      crystals. Improving the emission controllability is crucial for their practical
      applications. However, it is difficult because the closely adjacent laser
      components cannot be effectively adjusted by the traditional resonator design. In
      this paper, the anisotropy of laser emission in a monoclinic, disordered crystal
      Nd:LuYSiO(5) (Nd:LYSO) is reported for the first time. By selecting crystal
      orientation, high power laser emission with different wavelengths and
      polarizations were obtained. For X-cut sample, 1076 nm single-wavelength laser
      output reached 7.56 W, which will be a useful light source for detecting carbonyl
      hemoglobin and nitrite after frequency doubling. For Y- and Z-cut samples, 1076,
      1079 nm dual-wavelength laser output reached 10.3 W and 7.61 W, with parallel and
      orthogonal polarizations, respectively, which are convenient to be used as the
      generation sources of 0.78 THz wave by type-I or type-II difference frequency.
      The output characteristic is well explained by a theoretical analysis on the
      stimulated emission cross-section. The present work reveals that the intrinsic
      anisotropy in disordered laser crystal can be utilized to elevate the emission
      controllability. Accordantly, the material's application scopes can be extended.

PMID- 24663516
TI  - Application of a novel SSFBG-based single-input multiple-output encoder/decoder
      to optical packet switching.
AB  - We propose a novel superstructured fiber Bragg grating (SSFBG) based single-input
      multiple-output (SIMO) en/decoder, which can simultaneously process a group of
      independent optical codes with a specific permutation and combination of code
      patterns and spatially separate encoded and decoded signals into different
      optical paths. The number of optical codes processed by the SIMO en/decoder can
      be flexibly changed. We theoretically and experimentally investigate the coding
      performance of the SIMO en/decoder and discuss the unique features of the
      proposed device. In the experiment, we employ the SIMO en/decoder for optical
      label processing in an optical-code based optical packet switching system with
      the data rate of 10 Gbit/s and the packet rate of 312.5 MHz. The four-SSFBG based
      SIMO en/decoder are capable of simultaneously generating/recognizing four 31-chip
      640 Gchip/s optical code based labels and distribute the labels into four
      designated destinations. 

PMID- 24663517
TI  - Guided mode resonance enabled ultra-compact Germanium photodetector for 1.55 MUm
      detection.
AB  - We propose a novel technique of enhancing the photodetection capabilities of
      ultrathin Ge films for normally incident light at 1.55 MUm through the guided
      mode resonance (GMR) phenomenon. Specifically, by suitably patterning the surface
      of a Ge thin film, it is possible to excite guided modes which are subsequently
      coupled to free space radiative modes, resulting in spectral resonances that
      possess locally enhanced near fields with a large spatial extent. Absorption is
      found to be enhanced by over an order of magnitude over a pristine Ge film of
      equal thickness. Furthermore, attenuation of incident light for such a structure
      occurs over very few grating periods, resulting in significantly enhanced
      theoretical 3 dB bandwidth-efficiency products of ~58 GHz. The nature of the
      enhancement mechanism also produces spectrally narrow resonances (FWHM ~30 nm)
      that are polarization sensitive and exhibit excellent angular tolerance. Finally,
      the proposed device architecture is fully compatible with existing Si
      infrastructure and current CMOS fabrication processes. 

PMID- 24663518
TI  - Continuous-wave terahertz system based on a dual-mode laser for real-time non
      contact measurement of thickness and conductivity.
AB  - Terahertz (THz) waves have been exploited for the non-contact measurements of
      thickness and refractive index, which has enormous industrial applicability. In
      this work, we demonstrate a 1.3-MUm dual-mode laser (DML)-based continuous-wave
      THz system for the real-time measurement of a commercial indium-tin-oxide (ITO)
      coated glass. The system is compact, cost-effective, and capable of performing
      broadband measurement within a second at the setting resolution of 1 GHz. The
      thickness of the glass and the sheet conductivity of the ITO film were
      successfully measured, and the measurements agree well with those of broadband
      pulse-based time domain spectroscopy and Hall measurement results. 

PMID- 24663519
TI  - Self-action of continuous laser radiation and Pearcey diffraction in a water
      suspension with light-absorbing particles.
AB  - Water suspension of light-absorbing nano-sized particles is an example of a
      medium in which non-linear effects are present at moderate light intensities
      favorable for optical treatment of organic and biological objects. We study
      experimentally the phenomena emerging in a thin layer of such a medium under the
      action of inhomogeneous light field formed due to the Pearcey diffraction pattern
      near a microlens focus. In this high-gradient field, the light energy absorbed by
      the particles induces inhomogeneous distribution of the medium refraction index,
      which results in observable self-diffraction of the incident light, here being
      strongly sensitive to the medium position with respect to the focus. This
      technique, based on the complex spatial structure of both the incident and the
      diffracted fields, can be employed for the detection and measurement of weak non
      linearities. 

PMID- 24663520
TI  - Terabit bandwidth-adaptive transmission using low-complexity format-transparent
      digital signal processing.
AB  - In this paper, we propose a low-complexity format-transparent digital signal
      processing (DSP) scheme for next generation flexible and energy-efficient
      transceiver. It employs QPSK symbols as the training and pilot symbols for the
      initialization and tracking stage of the receiver-side DSP, respectively, for
      various modulation formats. The performance is numerically and experimentally
      evaluated in a dual polarization (DP) 11 Gbaud 64QAM system. Employing the
      proposed DSP scheme, we conduct a system-level study of Tb/s bandwidth-adaptive
      superchannel transmissions with flexible modulation formats including QPSK, 8QAM
      and 16QAM. The spectrum bandwidth allocation is realized in the digital domain
      instead of turning on/off sub-channels, which improves the performance of higher
      order QAM. Various transmission distances ranging from 240 km to 6240 km are
      demonstrated with a colorless detection for hardware complexity reduction. 

PMID- 24663521
TI  - Low-loss flexible bilayer metamaterials in THz regime.
AB  - Low insertion-loss single-layer and bilayer metamaterial filters in terahertz
      (THz) frequency regime were demonstrated on top of low cost flexible Scotch tape
      by utilizing pattern transfer method. The transmittance of the flexible 51-MUm
      thick Scotch tape was found out to be higher than 0.85 in the range of 0.2 to 3
      THz, which is excellent for the substrate materials for THz applications. Free
      standing filters exhibited record low insertion loss of 0.6 dB and band rejection
      ratio as high as 30 dB. The resonance reflection characteristics of the bilayer
      filters were maintained when they were attached on top of curved PET bottle or
      metallic surfaces, providing promising application in THz identifications. 

PMID- 24663522
TI  - OFDR with double interrogation for dynamic quasi-distributed sensing.
AB  - A method for phase sensitive quasi-distributed vibration and acoustical sensing
      is presented. The method is based on double optical frequency domain
      reflectometry interrogation of a sensing fiber with an array of discrete weak
      reflectors. Two replicas of the interrogation signal are launched into the
      sensing fiber. The time delay between the replicas is equal to the roundtrip time
      between two consecutive reflectors. Each peak in the spectrum of the returning
      signal is made from a coherent addition of the reflections of two consecutive
      reflectors. Its magnitude is highly sensitive to the optical phase in the fiber
      segment between the reflectors. The system was used to detect and locate the fall
      of a paperclip from height of 40 cm onto a sandbox where a 15 cm segment of the
      fiber was buried. In a different experiment the system successfully detected and
      located minute vibrations at 440 Hz that were induced by touching the fiber with
      a tuning fork.

PMID- 24663523
TI  - A simple method for astigmatic compensation of folded resonator without Brewster
      window.
AB  - A folded resonator requires an oblique angle of incidence on the folded curved
      mirror, which introduces astigmatic distortions that limit the performance of the
      lasers. We present a simple method to compensate the astigmatism of folded
      resonator without Brewster windows for the first time to the best of our
      knowledge. Based on the theory of the propagation and transformation of Gaussian
      beams, the method is both effective and reliable. Theoretical results show that
      the folded resonator can be compensated astigmatism completely when the following
      two conditions are fulfilled. Firstly, when the Gaussian beam with a determined
      size beam waist is obliquely incident on an off-axis concave mirror, two new
      Gaussian beam respectively in the tangential and sagittal planes are formed.
      Another off-axis concave mirror is located at another intersection point of the
      two new Gaussian beams. Secondly, adjusting the incident angle of the second
      concave mirror or its focal length can make the above two Gaussian beam coincide
      in the image plane of the second concave mirror, which compensates the astigmatic
      aberration completely. A side-pumped continues-wave (CW) passively mode locked
      Nd:YAG laser was taken as an example of the astigmatically compensated folded
      resonators. The experimental results show good agreement with the theoretical
      predictions. This method can be used effectively to design astigmatically
      compensated cavities resonator of high-performance lasers. 

PMID- 24663524
TI  - Suspended GaN-based band-edge type photonic crystal nanobeam cavities.
AB  - We demonstrated GaN-based photonic crystal (PC) nanobeam cavities by using the e
      beam lithography and the suspended nanobeams were realized by focused-ion beam
      (FIB) milling. One resonant mode was clearly observed at 411.7 nm at 77K by
      optical pumping. The quality factor was measured to be to 7.4 * 10(2). Moreover,
      the degree of polarization value was measured to be 40%. The temperature
      dependent characteristics were measured and discussed, which unambiguously
      demonstrated that the observed resonant peak originated from the band-edge mode
      of the one-dimensional PC nanobeam.

PMID- 24663525
TI  - Multiwavefront digital holographic television.
AB  - This paper presents the full technology chain supporting wide angle digital
      holographic television from holographic capture of real world objects/scenes to
      holographic display with an extended viewing angle. The data are captured with
      multiple CCD cameras located around an object. The display system is based on
      multiple tilted spatial light modulators (SLMs) arranged in a circular
      configuration. The capture-display system is linked by a holographic data
      processing module, which allows for significant decoupling of the capture and
      display systems. The presented experimental results, based on the reconstruction
      of real world, variable in time scenes, illustrates imaging dynamics, viewing
      angle and quality. 

PMID- 24663526
TI  - Design of highly efficient metallo-dielectric patch antennas for single-photon
      emission.
AB  - Quantum emitters such as NV-centers or quantum dots can be used as single-photon
      sources. To improve their performance, they can be coupled to microcavities or
      nano-antennas. Plasmonic antennas offer an appealing solution as they can be used
      with broadband emitters. When properly designed, these antennas funnel light into
      useful modes, increasing the emission rate and the collection of single-photons.
      Yet, their inherent metallic losses are responsible for very low radiative
      efficiencies. Here, we introduce a new design of directional, metallo-dielectric,
      optical antennas with a Purcell factor of 150, a total efficiency of 74% and a
      collection efficiency of emitted photons of 99%. 

PMID- 24663527
TI  - Experimental bifurcation-cascade diagram of an external-cavity semiconductor
      laser.
AB  - This Letter is the first to report experimental bifurcation diagrams of an
      external-cavity semiconductor laser (ECSL) in the low-to-moderate current
      injection regime and long-cavity case. Based on the bifurcation cascade behavior
      which was unveiled by Hohl and Gavrielides [Phys. Rev. Lett. 82, 1148-1151
      (1999)], we present a detailed experimental investigation of the nonlinear
      dynamics of ECSLs and of the robustness of the cascade to changes in the current
      and cavity length. Also, we report for the first time a well resolved
      experimental Hopf bifurcation in an ECSL. Based on the Lang and Kobayashi model,
      we identify the dynamical regimes and the instabilities involved in the cascade,
      as well as the influence of the current and cavity length on the cascade. 

PMID- 24663528
TI  - Dual-color fluorescence cross-correlation spectroscopy on a single plane
      illumination microscope (SPIM-FCCS).
AB  - Single plane illumination microscopy based fluorescence correlation spectroscopy
      (SPIM-FCS) is a new method for imaging FCS in 3D samples, providing diffusion
      coefficients, flow velocities and concentrations in an imaging mode. Here we
      extend this technique to two-color fluorescence cross-correlation spectroscopy
      (SPIM-FCCS), which allows to measure molecular interactions in an imaging mode.
      We present a theoretical framework for SPIM-FCCS fitting models, which is
      subsequently used to evaluate several test measurements of in-vitro (labeled
      microspheres, several DNAs and small unilamellar vesicles) and in-vivo samples
      (dimeric and monomeric dual-color fluorescent proteins, as well as membrane bound
      proteins). Our method yields the same quantitative results as the well
      established confocal FCCS, but in addition provides unmatched statistics and true
      imaging capabilities. 

PMID- 24663529
TI  - Waveguide-coupled photonic crystal cavity for quantum dot spin readout.
AB  - We present a waveguide-coupled photonic crystal H1 cavity structure in which the
      orthogonal dipole modes couple to spatially separated photonic crystal
      waveguides. Coupling of each cavity mode to its respective waveguide with equal
      efficiency is achieved by adjusting the position and orientation of the
      waveguides. The behavior of the optimized device is experimentally verified for
      where the cavity mode splitting is larger and smaller than the cavity mode
      linewidth. In both cases, coupled Q-factors up to 1600 and contrast ratios up to
      10 are achieved. This design may allow for spin state readout of a self-assembled
      quantum dot positioned at the cavity center or function as an ultra-fast optical
      switch operating at the single photon level. 

PMID- 24663530
TI  - Pre-configured polyhedron based protection against multi-link failures in optical
      mesh networks.
AB  - This paper focuses on random multi-link failures protection in optical mesh
      networks, instead of single, the dual or sequential failures of previous studies.
      Spare resource efficiency and failure robustness are major concerns in link
      protection strategy designing and a k-regular and k-edge connected structure is
      proved to be one of the optimal solutions for link protection network. Based on
      this, a novel pre-configured polyhedron based protection structure is proposed,
      and it could provide protection for both simultaneous and sequential random link
      failures with improved spare resource efficiency. Its performance is evaluated in
      terms of spare resource consumption, recovery rate and average recovery path
      length, as well as compared with ring based and subgraph protection under
      probabilistic link failure scenarios. Results show the proposed novel link
      protection approach has better performance than previous works. 

PMID- 24663531
TI  - Real-Space x-ray tomographic reconstruction of randomly oriented objects with
      sparse data frames.
AB  - Schemes for X-ray imaging single protein molecules using new x-ray sources, like
      x-ray free electron lasers (XFELs), require processing many frames of data that
      are obtained by taking temporally short snapshots of identical molecules, each
      with a random and unknown orientation. Due to the small size of the molecules and
      short exposure times, average signal levels of much less than 1
      photon/pixel/frame are expected, much too low to be processed using standard
      methods. One approach to process the data is to use statistical methods developed
      in the EMC algorithm (Loh & Elser, Phys. Rev. E, 2009) which processes the data
      set as a whole. In this paper we apply this method to a real-space tomographic
      reconstruction using sparse frames of data (below 10(-2) photons/pixel/frame)
      obtained by performing x-ray transmission measurements of a low-contrast,
      randomly-oriented object. This extends the work by Philipp et al. (Optics
      Express, 2012) to three dimensions and is one step closer to the single molecule
      reconstruction problem.

PMID- 24663532
TI  - Luminescence and photosensitivity of gadolinium labeled hematoporphyrin
      monomethyl ether.
AB  - Photodynamic therapy for deep-lying lesions needs an appropriate imaging
      modality, precise evaluation of tissue oxygen and an effective photosensitizer.
      Gadolinium based metalloporphyrins Gd(III)-HMME is proposed in this study as a
      potential multifunctional theranostic agent, as photosensitizer, ratiometric
      oxygen sensor and MRI contrast agent. The time resolved spectroscopy revealed the
      luminescence peak of Gd(III)-HMME at 710 and 779 nm with a lifetime of 64 MUs in
      oxygen-free methanol to be phosphorescent. This phosphorescence is strongly
      dependent on dissolved oxygen concentration. Its intensity in oxygen saturated
      methanol solution is 21% of that in deoxygenated solution. The singlet oxygen
      quantum yields PhiDelta of HMME and Gd(III)-HMME in air saturated methanol
      solution were determined to be 0.79 and 0.40 respectively using comparative
      spectra method. These phenomena indicate that the oxygen sensibility and
      production of singlet oxygen of Gd(III)-HMME can fulfill the requirement of PDT
      treatment.

PMID- 24663533
TI  - Wavelength-switchable mode-locked Yb:LuAG laser between 1031 nm and 1046 nm.
AB  - We experimentally demonstrated a wavelength switchable passively mode-locked
      Yb:LuAG laser. The mode locked laser wavelength could be switched between 1031 nm
      and 1046 nm by a slit. With a coupler of 2% transmission, mode locked pulses with
      pulse duration of 1.15 ps and average output power of 1.3 W were generated at
      1031 nm. By simply translating the slit position, 1046-nm mode locked pulses were
      generated with pulse duration of 252 fs and average output power of 676 mW. With
      the output coupler of 8% transmission, higher average output power of 2.2 W was
      generated at 1031 nm with pulse duration of 1.8 ps, which is the highest average
      output power ever reported for Yb:LuAG mode-locked lasers.

PMID- 24663534
TI  - Homogenization of quasi-1d metamaterials and the problem of extended bandwidth.
AB  - We derive approximate analytical expressions for the effective permittivity
      tensor of two-phase metamaterials whose geometry is close to one-dimensional
      (quasi-one-dimensional metamaterials). Specifically, we consider the metamaterial
      made of parallel slabs with width given by a linear or parabolic function. Using
      our approach, the design of epsilon-near-zero, ultra-low and high refractive
      index metallodielectric metamaterials with extended bandwidth has been
      demonstrated. In addition, generalizations to the three-dimensional case and some
      limitations of the presented technique are briefly considered. 

PMID- 24663535
TI  - A miniature reflective micro-force sensor based on a microfiber coupler.
AB  - A compact highly sensitive microfiber coupler based reflective micro-force sensor
      is presented. The device is fabricated by fusing two twisted optical fibers and
      then connecting two of the pigtails to form a Sagnac loop. The sensor has a high
      force sensitivity of ~3754 nm/N which is three orders of magnitude larger than
      traditional optical fiber force sensors, and a low detection limit of ~1.6 uN.
      The good repeatability is also shown in this paper. 

PMID- 24663536
TI  - Multi-peak-spectra generation with Cherenkov radiation in a non-uniform single
      mode fiber.
AB  - We propose, by means of numerical simulations, a simple method to design a non
      uniform standard single mode fiber to generate spectral broadening in the form of
      "ad-hoc" chosen peaks from dispersive waves. The controlled multi-peak generation
      is possible by an on/off switch of Cherenkov radiation, achieved by tailoring the
      fiber dispersion when decreasing the cladding diameter by segments. The interplay
      between the fiber dispersion and the soliton self-frequency shift results in
      discrete peaks of efficiently emitted Cherenkov radiation from low order
      solitons, despite the small amount of energy contained in a pulse. These spectra
      are useful for applications that demand low power bell-shaped pulses at specific
      carrier wavelengths. 

PMID- 24663537
TI  - Monolithic fiber chirped pulse amplification system for millijoule femtosecond
      pulse generation at 1.55 um.
AB  - A monolithic fiber chirped pulse amplification system that generates sub-500 fs
      pulses with 913 uJ pulse energy and 4.4 W average power at 1.55 um wavelength has
      recently been demonstrated. The estimated peak power for the system output
      approached 1.9 GW. The pulses were near diffraction-limited and near transform
      limited, benefiting from the straight and short length of the booster amplifier
      as well as adaptive phase shaping for the overall mitigation of the nonlinear
      phase accumulation. The booster amplifier employs an Er(3+)-doped large mode area
      high efficiency media fiber just 28 cm in length with a fundamental mode (LP(01))
      diameter of 54 um and a corresponding effective mode area of 2290 um(2).

PMID- 24663539
TI  - First demonstration of high-order QAM signal amplification in PPLN-based phase
      sensitive amplifier.
AB  - We demonstrate the phase sensitive amplification of a high-order quadrature
      amplitude modulation (QAM) signal using non-degenerate parametric amplification
      in a periodically poled lithium niobate (PPLN) waveguide. The interaction between
      the pump, signal, and phase-conjugated idler enables us to amplify arbitrary
      phase components of the signal. The 16QAM signals are amplified without
      distortion because of the high gain linearity of the PPLN-based phase sensitive
      amplifier (PSA). Both the phase and amplitude noise reduction capabilities of the
      PSA are ensured. Phase noise cancellation is achieved by using the interaction
      with the phase-conjugated idler. A degraded signal-to-noise ratio (SNR) is
      restored by using the gain difference between a phase-correlated signal-idler
      pair and uncorrelated excess noise. The applicability of the simultaneous
      amplification of multi-carrier signals and the amplification of two independent
      polarization signals are also confirmed with a view to realizing ultra-high
      spectrally efficient signal amplification. 

PMID- 24663538
TI  - Novel flat datacenter network architecture based on scalable and flow-controlled
      optical switch system.
AB  - We propose and demonstrate an optical flat datacenter network based on scalable
      optical switch system with optical flow control. Modular structure with
      distributed control results in port-count independent optical switch
      reconfiguration time. RF tone in-band labeling technique allowing parallel
      processing of the label bits ensures the low latency operation regardless of the
      switch port-count. Hardware flow control is conducted at optical level by re
      using the label wavelength without occupying extra bandwidth, space, and network
      resources which further improves the performance of latency within a simple
      structure. Dynamic switching including multicasting operation is validated for a
      4 x 4 system. Error free operation of 40 Gb/s data packets has been achieved with
      only 1 dB penalty. The system could handle an input load up to 0.5 providing a
      packet loss lower that 10(-5) and an average latency less that 500 ns when a
      buffer size of 16 packets is employed. Investigation on scalability also
      indicates that the proposed system could potentially scale up to large port count
      with limited power penalty.

PMID- 24663540
TI  - Fabrication of highly stable silica coated ZnCuInS nanocrystals monolayer via
      layer by layer deposition for LED application.
AB  - In this study, non-toxic and highly stable silica coated ZnCuInS NCs were
      synthesized by a reverse microemulsion method. The single NCs were uniformly
      encapsulated in a silica shell with a diameter of ~30 nm. Although hydrolyzed
      TEOS caused a QY reduction, and a 12.5 nm red shift occurred after silica
      coating, the photo and thermal stabilities were extremely improved. For LED
      application, the silica coated ZnCuInS NCs phosphor layer was arrayed on the
      InGaN LED surface by layer-by-layer deposition utilizing electrostatic
      attraction. When the ZnCuInS/SiO2 NCs single monolayer was fabricated, 6.73% high
      color conversion efficiency was achieved.

PMID- 24663541
TI  - CMOS-compatible highly efficient polarization splitter and rotator based on a
      double-etched directional coupler.
AB  - We present a highly efficient polarization splitter and rotator (PSR), fabricated
      using 248 nm deep ultraviolet lithography on a silicon-on-insulator substrate.
      The PSR is based on a double-etched directional coupler with a length of 27 um.
      The fabricated PSR yields a TM-to-TE conversion loss better than 0.5 dB and TE
      insertion loss better than 0.3 dB, with an ultra-low crosstalk (-20 dB) in the
      wavelength regime 1540-1570 nm. 

PMID- 24663542
TI  - Automated identification and classification of single particle serial femtosecond
      X-ray diffraction data.
AB  - The first hard X-ray laser, the Linac Coherent Light Source (LCLS), produces 120
      shots per second. Particles injected into the X-ray beam are hit randomly and in
      unknown orientations by the extremely intense X-ray pulses, where the femtosecond
      duration X-ray pulses diffract from the sample before the particle structure is
      significantly changed even though the sample is ultimately destroyed by the
      deposited X-ray energy. Single particle X-ray diffraction experiments generate
      data at the FEL repetition rate, resulting in more than 400,000 detector readouts
      in an hour, the data stream during an experiment contains blank frames mixed with
      hits on single particles, clusters and contaminants. The diffraction signal is
      generally weak and it is superimposed on a low but continually fluctuating
      background signal, originating from photon noise in the beam line and electronic
      noise from the detector. Meanwhile, explosion of the sample creates fragments
      with a characteristic signature. Here, we describe methods based on rapid image
      analysis combined with ion Time-of-Flight (ToF) spectroscopy of the fragments to
      achieve an efficient, automated and unsupervised sorting of diffraction data. The
      studies described here form a basis for the development of real-time frame
      rejection methods, e.g. for the European XFEL, which is expected to produce 100
      million pulses per hour. 

PMID- 24663543
TI  - A fully-integrated 12.5-Gb/s 850-nm CMOS optical receiver based on a spatially
      modulated avalanche photodetector.
AB  - We present a fully integrated 12.5-Gb/s optical receiver fabricated with standard
      0.13-um complementary metal-oxide-semiconductor (CMOS) technology for 850-nm
      optical interconnect applications. Our integrated optical receiver includes a
      newly proposed CMOS-compatible spatially-modulated avalanche photodetector, which
      provides larger photodetection bandwidth than previously reported CMOS-compatible
      photodetectors. The receiver also has high-speed CMOS circuits including
      transimpedance amplifier, DC-balanced buffer, equalizer, and limiting amplifier.
      With the fabricated optical receiver, detection of 12.5-Gb/s optical data is
      successfully achieved at 5.8 pJ/bit. Our receiver achieves the highest data rate
      ever reported for 850-nm integrated CMOS optical receivers. 

PMID- 24663544
TI  - Molecular photoelectron holography with circularly polarized laser pulses.
AB  - We investigate the photoelectron momentum distribution of molecular-ion H2+driven
      by ultrashort intense circularly polarized laser pulses. Both numerical solutions
      of the time-dependent Schrodinger equation (TDSE) and a quasiclassical model
      indicate that the photoelectron holography (PH) with circularly polarized pulses
      can occur in molecule. It is demonstrated that the interference between the
      direct electron wave and rescattered electron wave from one core to its
      neighboring core induces the PH. Moreover, the results of the TDSE predict that
      there is a tilt angle between the interference pattern of the PH and the
      direction perpendicular to the molecular axis. Furthermore, the tilt angle is
      sensitively dependent on the wavelength of the driven circularly polarized pulse,
      which is confirmed by the quasiclassical calculations. The PH induced by
      circularly polarized laser pulses provides a tool to resolve the electron
      dynamics and explore the spatial information of molecular structures. 

PMID- 24663545
TI  - Demonstration of broad photonic crystal stop band in a freely-suspended
      microfiber perforated by an array of rectangular holes.
AB  - It is shown that photonic crystal (PhC) optical reflectors with reflectance in
      excess of 60% and fractional bandwidths greater than 10% can be fabricated by ion
      beam milling of fewer than ten periods of rectangular cross section through-holes
      in micron-scale tapered fibers. The optical characteristics agree well with
      numerical simulations when allowance is made for fabrication artefacts and we
      show that the radiation loss, which is partly determined by optical interference,
      can be suppressed by design. The freely-suspended devices are compact and robust
      and could form the basic building block of optical cavities and filters. 

PMID- 24663546
TI  - Stimulated emission in GaN-based laser diodes far below the threshold region.
AB  - We identify that the stimulated emission of GaN laser diodes (LDs) emerges far
      below the traditionally recognized threshold from both optical and electrical
      experiments. Below the threshold, the linear-polarized stimulated emission has
      been the dominating part of overall emission and closely related to resonant
      cavity. Its intensity increases super linearly with current while that of
      spontaneous emission increases almost linearly. Moreover, the separation of quasi
      Fermi levels of electrons and holes across the active region has already exceeded
      the photon emission energy, namely, realized the population-inversion. 

PMID- 24663547
TI  - Tilted MMI crossings based on silicon wire waveguide.
AB  - Waveguide crossings employing tilted MMI structures on silicon wire waveguide are
      proposed and demonstrated. Intersecting angle of the two MMI waveguides is
      optimized for low crosstalk. The optimization is carried out with input
      polarizations specified. On the fabricated MMI crossings, crosstalk lower than 
      38 dB in the C-band was experimentally confirmed. A novel polarization
      insensitive crossing based on a diversity circuit was fabricated. Crosstalk lower
      than -30 dB in the C-band is demonstrated. 

PMID- 24663548
TI  - Generation of frequency degenerate twin photons in pulse pumped fiber optical
      parametric amplifiers: influence of background noise.
AB  - Using a Sagnac fiber loop functions as a deterministic splitter of photon pairs
      produced by the frequency degenerate four wave mixing, we show that the
      background noise of the degenerate photon pairs is contributed by both Raman
      scattering and frequency non-degenerate four wave mixing. To improve the purity
      of photon pairs in the high gain regime, in addition to suppressing the noise
      photons by cooling the nonlinear fiber and by optimizing the detuning between the
      frequencies of the pump and photon pairs, the walk-off effect of the two pulsed
      pump fields should be mitigated by managing the dispersion of the fiber. Our
      investigation is not only the first step towards the generation of multi-mode
      squeezed vacuum in fiber optical parametric amplifiers pumped with pulsed lights,
      but also contributes to improving the purity of the fiber sources of degenerate
      photon pairs. 

PMID- 24663549
TI  - Plane wave expansion method used to engineer photonic crystal sensors with high
      efficiency.
AB  - A photonic crystal waveguide (PhC-WG) was reported to be usable as an optical
      sensor highly sensitive to various material parameters, which can be detected via
      changes in transmission through the PhC-WG caused by small changes of the
      refractive index of the medium filling its holes. To monitor these changes
      accurately, a precise optical model is required, for which the plane wave
      expansion (PWE) method is convenient. We here demonstrate the revision of the PWE
      method by employing the complex Fourier factorization approach, which enables the
      calculation of dispersion diagrams with fast convergence, i.e., with high
      precision in relatively short time. The PhC-WG is proposed as a line defect in a
      hexagonal array of cylindrical holes periodically arranged in bulk silicon,
      filled with a variable medium. The method of monitoring the refractive index
      changes is based on observing cutoff wavelengths in the PhC-WG dispersion
      diagrams. The PWE results are also compared with finite-difference time-domain
      calculations of transmittance carried out on a PhC-WG with finite dimensions. 

PMID- 24663550
TI  - High-power Faraday isolators based on TAG ceramics.
AB  - The Faraday isolator based on a new magneto-optical medium--TAG (terbium aluminum
      garnet) ceramics was implemented and investigated experimentally. The magneto
      optical element was temperature-stabilized using water cooling. The device
      provides a stable isolation ratio of 38 dB at 300 W laser power. Estimates show
      high performance of the device at a kilowatt laser power.

PMID- 24663551
TI  - Laser absorption spectroscopy of oxygen confined in highly porous hollow sphere
      xerogel.
AB  - An Al2O3 xerogel with a distinctive microstructure is studied for the application
      of laser absorption spectroscopy of oxygen. The xerogel has an exceptionally high
      porosity (up to 88%) and a large pore size (up to 3.6 um). Using the method of
      gas-in-scattering media absorption spectroscopy (GASMAS), a long optical path
      length (about 3.5m) and high enhancement factor (over 300 times) are achieved as
      the result of extremely strong multiple-scattering when the light is transmitted
      through the air-filled, hollow-sphere alumina xerogel. We investigate how the
      micro-physical feature influences the optical property. As part of the optical
      sensing system, the material's gas exchange dynamics are also experimentally
      studied.

PMID- 24663552
TI  - First field demonstration of cloud datacenter workflow automation employing
      dynamic optical transport network resources under OpenStack and OpenFlow
      orchestration.
AB  - For the first time, we demonstrate the orchestration of elastic datacenter and
      inter-datacenter transport network resources using a combination of OpenStack and
      OpenFlow. Programmatic control allows a datacenter operator to dynamically
      request optical lightpaths from a transport network operator to accommodate rapid
      changes of inter-datacenter workflows. 

PMID- 24663553
TI  - Parallel femtosecond laser ablation with individually controlled intensity.
AB  - The use of computer generated holograms together with spatial light modulator
      (SLM) enable highly parallel laser micromachining. Usually SLM is used for
      splitting the original laser beam to desired number of beams with equal
      intensity. However, this technique also enables that the intensity of every beam
      can be controlled individually. Example of the hologram designing procedure for
      separation of the original beam to 400 beams with individually controlled
      intensity is presented. The proposed technique is demonstrated by femtosecond
      laser ablation of grayscale pictures so that grey scale of the pixel is addressed
      with corresponding beam intensity in the ablated picture. 

PMID- 24663554
TI  - Reconfigurable linear combination of phase-and-amplitude coded optical signals.
AB  - We introduce an all-optical arithmetic unit operating a weighted addition and
      subtraction between multiple phase-and-amplitude coded signals. The scheme
      corresponds to calculating the field dot-product of frequency channels with a
      static vector of coefficients. The system is reconfigurable and format
      transparent. It is based on Fourier-domain processing and multiple simultaneous
      four-wave mixing processes inside a single nonlinear element. We demonstrate the
      device with up to three channels at 40 Gb/s and evaluate its efficiency by
      measuring the bit-error-rate of a distortion compensation operation between two
      signals. 

PMID- 24663555
TI  - The impact of nonlinear losses in the silicon micro-ring cavities on CW pumping
      correlated photon pair generation.
AB  - In this paper, 1.5 MUm correlated photon pairs are generated under continuous
      wave (CW) pumping in a silicon micro-ring cavity with a Q factor of 8.1 * 10(4).
      The ratio of coincidences to accidental coincidences (CAR) is up to 200 under a
      coincidence time bin width of 5 ns. The experiment result of single side photon
      count shows that the generation rate does not increase as the square of the pump
      level due to the nonlinear losses in the cavity which reduce the Q factor and
      impact the field enhancement effect in the cavity under high pump level.
      Theoretical analysis shows that the photon pair generation rate in the cavity is
      proportional to the seventh power of the Q factor, which agrees well with the
      experiment result. It provides a way to analyze the performance of CW pumping
      correlated photon pair generation in silicon micro-ring cavities under high pump
      levels.

PMID- 24663556
TI  - Akinetic all-semiconductor programmable swept-source at 1550 nm and 1310 nm with
      centimeters coherence length.
AB  - We demonstrate, for the first time, OCT imaging capabilities of a novel, akinetic
      (without any form of movement in the tuning mechanism), all-semiconductor, all
      electronic tunable, compact and flexible swept source laser technology at 1550 nm
      and 1310 nm. To investigate its OCT performance, 2D and 3D ex vivo and in vivo
      OCT imaging was performed at different sweep rates, from 20 kHz up to 200 kHz,
      with different axial resolutions, about 10 um to 20 um, and at different
      coherence gate displacements, from zero delay to >17 cm. Laser source phase
      linearity and phase repeatability standard deviation of <2 mrad (<160 pm) were
      observed without external phase referencing, indicating that the laser operated
      close to the shot noise limit (~2 * factor); constant percentile wavelengths
      variations of sliding RIN and ortho RIN <0.2% could be demonstrated, ~5 times
      better as compared to other swept laser technologies.

PMID- 24663557
TI  - Time-resolved spectral characterization of ring cavity surface emitting and ridge
      type distributed feedback quantum cascade lasers by step-scan FT-IR spectroscopy.
AB  - We present the time-resolved comparison of pulsed 2nd order ring cavity surface
      emitting (RCSE) quantum cascade lasers (QCLs) and pulsed 1st order ridge-type
      distributed feedback (DFB) QCLs using a step-scan Fourier transform infrared (FT
      IR) spectrometer. Laser devices were part of QCL arrays and fabricated from the
      same laser material. Required grating periods were adjusted to account for the
      grating order. The step-scan technique provided a spectral resolution of 0.1 cm(
      1) and a time resolution of 2 ns. As a result, it was possible to gain
      information about the tuning behavior and potential mode-hops of the investigated
      lasers. Different cavity-lengths were compared, including 0.9 mm and 3.2 mm long
      ridge-type and 0.97 mm (circumference) ring-type cavities. RCSE QCLs were found
      to have improved emission properties in terms of line-stability, tuning rate and
      maximum emission time compared to ridge-type lasers.

PMID- 24663558
TI  - Engineering metal oxide nanostructures for the fiber optic sensor platform.
AB  - This paper presents an effective integration scheme of nanostructured SnO2 with
      the fiber optic platform for chemical sensing applications based on evanescent
      optical interactions. By using a triblock copolymer as a structure directing
      agent as the means of nano-structuring, the refractive index of SnO2 is reduced
      from >2.0 to 1.46, in accordance with effective medium theory for optimal on
      fiber integration. High-temperature stable fiber Bragg gratings inscribed in D
      shaped fibers were used to perform real-time characterization of optical
      absorption and refractive index modulation of metal oxides in response to NH3
      from the room temperature to 500  degrees C. Measurement results reveals that the
      redox reaction of the nanostructured metal oxides exposed to a reactive gas NH3
      induces much stronger changes in optical absorption as opposed to changes in the
      refractive index. Results presented in this paper provide important guidance for
      fiber optic chemical sensing designs based on metal oxide nanomaterials.

PMID- 24663559
TI  - Laser-assisted lateral optical fiber processing for selective infiltration.
AB  - We propose a new technique to perform precise selective infiltration of an air
      hole in the photonic crystal fiber (PCF). To carry out the infiltration process,
      the end face of the PCF is covered by a mask, which is fabricated by femtosecond
      laser inscription from the lateral direction. This proposed method overcomes the
      conventional limitation of maximum mask thickness. An analytical model is further
      proposed and demonstrated accurate determinations of the fabricated channel
      diameter in the mask. 

PMID- 24663560
TI  - Electrically pumped hybrid plasmonic waveguide.
AB  - Active plasmonic waveguiding has become a key requirement for designing and
      implementing nanophotonic devices. We study theoretically the performance of an
      Au/GaSb-based, metal-insulator-semiconductor (MIS) structure acting as a hybrid
      electrically pumped waveguide with gain. The surface-plasmon polariton (SPP) mode
      supported by this configuration is analyzed in the third telecommunication window
      and discussed in detail. Changes in the effective mode index, confinement factor
      and effective mode area are illustrated for different core widths and layer
      thicknesses. Electrical behavior of the MIS junction is analyzed using a self
      consistent numerical technique and used to study variations in the material and
      model gains within the semiconducting region of the device. Our results indicate
      the possibility of achieving low loss SPP propagation while maintaining a strong
      field confinement. 

PMID- 24663561
TI  - Spatial quasi-phase-shifting technique for single-frame dynamic fringe analysis.
AB  - Phase demodulation from carrier-frequency fringe patterns is the core of many
      optic measurements. We propose spatial quasi-phase-shifting technique by
      expressing the fringe signal in the frequency-modulated form, which requires only
      one frame fringe pattern for instantaneous and dynamic measurements. In an area
      smaller than a fringe period, there substantially exists an approximately
      constant phase shift between spatially adjacent sample points. The technique is
      capable of demodulating the phase with such intra-frame phase shifts, which makes
      the instantaneous and dynamic measurement possible. The technique implements
      demodulation within three spatially adjacent neighbors, achieving spatial
      localization as good as a several-point level. Both numerical simulation and
      experiment are presented to verify its performance. 

PMID- 24663562
TI  - Reconfigurable spatially-diverse optical vector network analyzer.
AB  - We present a spatially-diverse optical vector network analyzer which is capable
      of measuring the partial or complete mode transfer matrix of a system as a
      function of wavelength in an arbitrary mode basis using single or multiple
      sweeps. 

PMID- 24663563
TI  - High-resistance liquid-crystal lens array for rotatable 2D/3D autostereoscopic
      display.
AB  - A 2D/3D switchable and rotatable autostereoscopic display using a high-resistance
      liquid-crystal (Hi-R LC) lens array is investigated in this paper. Using high
      resistance layers in an LC cell, a gradient electric-field distribution can be
      formed, which can provide a better lens-like shape of the refractive-index
      distribution. The advantages of the Hi-R LC lens array are its 2D/3D
      switchability, rotatability (in the horizontal and vertical directions), low
      driving voltage (~2 volts) and fast response (~0.6 second). In addition, the Hi-R
      LC lens array requires only a very simple fabrication process. 

PMID- 24663564
TI  - Modeling and optimization of photonic crystal devices based on transformation
      optics method.
AB  - In this paper, we propose a method for designing Photonic Crystal (PhC) devices
      that consist of dielectric rods with varying size. In the proposed design method,
      PhC devices are modeled with the Transformation Optics (TO) approach, and then
      they are optimized using the gradient method. By applying the TO technique, the
      original device model is transformed into an equivalent model that consists of
      uniform and fixed-sized rods, with parameterized permittivity and permeability
      distributions. Therefore, mesh refinement around small rods can be avoided, and
      PhC devices can be simulated more efficiently. In addition, gradient of the
      optimization object function is calculated with the Adjoint-Variable Method
      (AVM), which is very efficient for optimizing devices subject to multiple design
      variables. The proposed method opens up a new avenue to design and optimize a
      variety of photonic devices for optical computing and information processing. 

PMID- 24663565
TI  - Impact of structural distortions on the performance of hollow-core photonic
      bandgap fibers.
AB  - We present a generic model for studying numerically the performance of hollow
      core photonic bandgap fibers (HC-PBGFs) with arbitrary cross-sectional
      distortions. Fully vectorial finite element simulations reveal that distortions
      beyond the second ring of air holes have an impact on the leakage loss and
      bandwidth of the fiber, but do not significantly alter its surface scattering
      loss which remains the dominant contribution to the overall fiber loss (providing
      that a sufficient number of rings of air holes (>= 5) are used). We have found
      that while most types of distortions in the first two rings are generally
      detrimental, enlarging the core defect while keeping equidistant and on a
      circular boundary the glass nodes surrounding the core may produce losses half
      those compared to "idealized" fiber designs and with no penalty in terms of the
      transmission bandwidth.

PMID- 24663566
TI  - A robust tool for photon source geometry measurements using the fractional Talbot
      effect.
AB  - A reliable measurement of beam coherence is important for optimal performance of
      a number of coherence methods being utilized at third-generation synchrotrons and
      free-electron lasers. Various approaches have been proposed in the past for
      determining the source size, and hence the degree of coherence; however they
      often require complex setups with perfect optics and suffer from undefined
      uncertainties. We present a robust tool for X-ray source characterization with a
      full quantitative uncertainty analysis for fast on-the-fly coherence
      measurements. The influence of three multilayer monochromator crystals on the
      apparent source size is evaluated using the proposed method. 

PMID- 24663567
TI  - A 10-Gbps optical WiMAX transport system.
AB  - A 10-Gbps optical worldwide interoperability for microwave access (WiMAX)
      transport system employing vertical cavity surface emitting laser (VCSEL) and
      spatial light modulator (SLM) with 16-quadrature amplitude modulation (QAM)
      orthogonal frequency-division multiplexing (OFDM) modulating signal is proposed.
      With the assistance of equalizer and low noise amplifier (LNA) at the receiving
      site, good bit error rate (BER) performance, clear constellation map, and clear
      eye diagram are achieved in the proposed systems. An optical WiMAX transport
      system, transmitting 16-QAM-OFDM signal over a 6-m free-space link, with a data
      rate of 10 Gbps is successfully demonstrated. Such a 10-Gbps optical WiMAX
      transport system would be attractive for providing services including Internet
      and telecommunication services. Our proposed system is suitable for the free
      space lightwave transport system in visible light communication (VLC)
      application. 

PMID- 24663568
TI  - A 2 D high accuracy slope measuring system based on a Stitching Shack Hartmann
      Optical Head.
AB  - We present a 2D Slope measuring System based on a Stitching Shack Hartmann
      Optical Head (SSH-OH) aiming to perform high accuracy optical metrology for X-ray
      mirrors. This system was developed to perform high-accuracy automated metrology
      for extremely high quality optical components needed for synchrotrons or Free
      Electrons Lasers (FEL), EUV lithography and x-ray astronomy with slope error
      accuracy better than 50 nrad rms. 

PMID- 24663569
TI  - Fabry-Perot cavity based on chirped sampled fiber Bragg gratings.
AB  - A novel kind of Fabry-Perot (FP) structure based on chirped sampled fiber Bragg
      grating (CSFBG) is proposed and demonstrated. In this structure, the regular
      chirped FBG (CFBG) that functions as reflecting mirror in the FP cavity is
      replaced by CSFBG, which is realized by chirping the sampling periods of a
      sampled FBG having uniform local grating period. The realization of such CSFBG
      FPs having diverse properties just needs a single uniform pitch phase mask and
      sub-micrometer precision moving stage. Compared with the conventional CFBG-FP, it
      becomes more flexible to design CSFBG-FPs of diverse functions, and the
      fabrication process gets simpler. As a demonstration, based on the same
      experimental facilities, FPs with uniform FSR (~73 pm) and chirped FSR (varying
      from 28 pm to 405 pm) are fabricated respectively, which shows good agreement
      with simulation results.

PMID- 24663570
TI  - Strong guided mode resonant local field enhanced visible harmonic generation in
      an azo-polymer resonant waveguide grating.
AB  - Guided mode resonance (GMR) enhanced second- and third-harmonic generation (SHG
      and THG) is demonstrated in an azo-polymer resonant waveguide grating (RWG),
      comprised of a poled azo-polymer layer on top of a textured SU8 substrate with a
      thin intervening layer of TiO2. Strong SHG and THG outputs are observed by
      matching either in-coming fundamental- or out-going harmonic-wavelength to the
      GMR wavelengths of the azo-polymer RWG. Without the azo-polymer coating, pure
      TiO2 RWGs, do not generate any detectable SHG using a fundamental beam peak
      intensity of 2 MW/cm(2). Without the textured TiO2 layer, a planar poled azo
      polymer layer results in 3650 times less SHG than the full nonlinear RWG
      structure under identical excitation conditions. Rigorous coupled-wave analysis
      calculations confirm that this enhancement of the nonlinear conversion is due to
      strong local electric fields that are generated at the interfaces of the TiO2 and
      azo-polymer layers when the RWG is excited at resonant wavelengths associated
      with both SHG and THG conversion processes.

PMID- 24663571
TI  - Gaussian-like dual-wavelength prescaled clock recovery with simultaneous
      frequency-doubled clock recovery using an optoelectronic oscillator.
AB  - A novel multifunctional frequency-doubling optoelectronic oscillator (FD-OEO)
      mainly based on a Mach-Zehnder modulator (MZM) cascaded with a phase modulator
      (PM) and a subsequent optical bandpass filter (OBPF) is proposed. We
      experimentally demonstrate simultaneous operations of frequency-doubled optical
      clock (FD-OC) recovery, low-duty-cycle dual-wavelength prescaled OC recovery and
      error-free fourfold time division demultiplexing with the proposed OEO injected
      with a 4 * 25-Gb/s optical time-division-multiplexing (OTDM) signal. We show that
      the proposed FD-OEO operates well for both the differential phase shift keying
      (DPSK) and on-off keying (OOK) modulation formats. The extracted dual-wavelength
      prescaled OC is proved to be nearly transform-limited with Gaussian-like shape.
      Furthermore, all four 25-Gb/s tributaries can be selectively demultiplexed by
      adjusting the phase shifters in the OEO loop. The power penalty at a bit error
      rate (BER) of 10(-9) is measured to be 2.4 dB, 1.2 dB for the best channel for
      DPSK signal and to be 2.5 dB, 1.1 dB for the best channel for OOK signal. In
      addition, as an extra benefit of the OEO, low-phase-noise prescaled electrical
      clock (EC) is also extracted.

PMID- 24663572
TI  - Conformational analysis of proteins with a dual polarisation silicon microring.
AB  - Optical microresonator biosensors have proven to be a valid tool to perform
      affinity analysis of a biological binding event. However, when these
      microresonators are excited with a single optical mode they can not distinguish
      between a thin dense layer of biomolecules or a thick sparse layer. This means
      the sensor is "blind" to changes in shape of bound biomolecules. We succeeded in
      exciting a Silicon-on-Insulator (SOI) microring with TE and TM polarisations
      simultaneously by using an asymmetrical directional coupler and as such were able
      to separately determine the thickness and the density (or refractive index) of a
      bound biolayer. A proof-of-concept is given by determining both parameters of
      deposited dielectric layers and by analysing the conformational changes of Bovine
      Serum Albumin (BSA) proteins due to a change in pH of the buffer.

PMID- 24663573
TI  - High efficiency reflective waveplates in the midwave infrared.
AB  - We demonstrate a high efficiency reflective waveplate which exhibits incidence
      angle dependent phase shift tuning capabilities in the midwave infrared. Using
      Finite Difference Time Domain (FDTD) modeling, the phase shift and reflection
      efficiency are simulated for a variety of geometrical parameters, the results of
      which are then employed to optimize design. Devices were fabricated and both the
      polarization and efficiency characteristics were measured and compared to FDTD
      simulations showing excellent agreement. Further, the potential for scalability
      to other wavelength ranges and the capability to generate an arbitrary phase
      shift are explored to demonstrate the versatility of our design. 

PMID- 24663574
TI  - Visible light communications: real time 10 Mb/s link with a low bandwidth polymer
      light-emitting diode.
AB  - This paper presents new experimental results on a polymer light-emitting diode
      based visible light communications system. For the first time we demonstrate a 10
      Mb/s link based on the on-off keying data format with real time equalization on a
      field programmable gate array. The 10 Mb/s transmission speed is available at a
      bit error rate less than 4.6 * 10(-3), which is the limit for forward error
      correction. At a BER of 10(-6) a transmission speed of 7 Mb/s is readily
      achievable.

PMID- 24663575
TI  - Multiwavelength generation in a random distributed feedback fiber laser using an
      all fiber Lyot filter.
AB  - Multiwavelength lasing in the random distributed feedback fiber laser is
      demonstrated by employing an all fiber Lyot filter. Stable multiwavelength
      generation is obtained, with each line exhibiting sub-nanometer line-widths. A
      flat power distribution over multiple lines is obtained, which indicates that the
      power between lines is redistributed in nonlinear mixing processes. The
      multiwavelength generation is observed both in first and second Stokes waves. 

PMID- 24663576
TI  - Heterodyne moire surface profilometry.
AB  - In this study, a novel moire fringe analysis technique is proposed for measuring
      the surface profile of an object. After applying a relative displacement between
      two gratings at a constant velocity, every pixel of CMOS camera can capture a
      heterodyne moire signal. The precise phase distribution of the moire fringes can
      be extracted using a one-dimensional fast Fourier transform (FFT) analysis on
      every pixel, simultaneously filtering the harmonic noise of the moire fringes.
      Finally, the surface profile of the tested objected can be generated by
      substituting the phase distribution into the relevant equation. The findings
      demonstrate the feasibility of this measuring method, and the measurement error
      was approximately 4.3 MUm. The proposed method exhibits the merits of the Talbot
      effect, projection moire method, FFT analysis, and heterodyne interferometry. 

PMID- 24663578
TI  - Flexible-textured polydimethylsiloxane antireflection structure for enhancing
      omnidirectional photovoltaic performance of Cu(In,Ga)Se2 solar cells.
AB  - Because of the Sun's movement across the sky, broadband and omnidirectional light
      harvesting is a major development in photovoltaic technology. This study reports
      the fabrication and characterization of flexible-textured polydimethylsiloxane
      (PDMS) film on Cu(In,Ga)Se2 (CIGS) solar cells, which is one of the simplest and
      cheapest peel-off processes for fabricating a three-dimensional structure. A cell
      containing a textured PDMS film enhanced the short-circuit current density from
      22.12 to 23.93 mA/cm2 in a simulated one-sun scenario. The omnidirectional
      antireflection of CIGS solar cells containing various PDMS films is also
      investigated. This study uses an angle-resolved reflectance spectroscope to
      investigate the omnidirectional and broadband optical properties of the proposed
      PDMS film. This improvement in light harvesting is attributable to the scattering
      of the PDMS film and the gradual refractive index profile between the PDMS
      microstructures and air. The flexible-textured PDMS film is suitable for creating
      an antireflective coating for a diverse range of photovoltaic devices.

PMID- 24663577
TI  - Tunable millimeter and sub-millimeter spectral response of textile metamaterial
      via resonant states.
AB  - We report on a new textile metamaterial created by adding metal wires directly
      into the polymer yarn. Split-ring resonator-like extended states are created.
      Simulations revealed that the extended states can be easily tuned via the
      geometry. Measurements of the transmittance spectrum as a function of the
      polarization angle in the low terahertz range were also performed and these peaks
      were ascribed to a polarization-dependent resonator model. The fabrics are viable
      candidates for flexible and deformable gigahertz and terahertz-enabled
      metamaterials. 

PMID- 24663579
TI  - Plasmonic waveguides based on symmetric and asymmetric T-shaped structures.
AB  - We describe the fabrication and characterization of plasmonic waveguides based on
      a periodic one-dimensional array of symmetric and asymmetric T-shaped structures.
      The devices are fabricated in a polymer resin using conventional 3D printing and
      subsequently overcoated with ~500 nm of Au. Using terahertz (THz) time-domain
      spectroscopy, we systematically measure the guided-wave transmission properties
      of the devices as a function of the different geometrical parameters. Through
      these measurements, we find that the resonance frequency associated with the
      lowest order mode depends primarily on the structure height and the cap width and
      appears to be independent of its lateral width. We also perform numerical
      simulations using the same geometrical parameters and find excellent agreement
      between experiment and simulation. We fabricate a waveguide in which the lateral
      width of the T-shaped structures is tapered in a linear fashion. While the
      spectrum of this device is similar to one without tapering, we observe relatively
      little reduction in the mode size, even as the structure width is reduced by a
      factor of eight. 

PMID- 24663580
TI  - Stokes and anti-Stokes differential pulse pair based distributed Brillouin fiber
      sensor with double-sideband probe wave.
AB  - We propose and demonstrate a distributed Brillouin fiber sensor using Stokes and
      anti-Stokes differential pulse pair based on double- sideband probe wave, in
      which the two sidebands of probe wave are used to balance the power of two pump
      pulses. The spatial resolution is determined by the slightly width difference of
      the two balanced pulses, without Brillouin gain spectrum broadening. The pulses
      perform gain-loss process in optical field before the probe signal being
      detected, without any post-processing or extra measurement time. The proposed
      technique can achieve high spatial resolution, natural Brillouin gain spectrum
      linewidth, normal measurement time and long sensing range simultaneously. 

PMID- 24663581
TI  - Contrast enhancement using silica microspheres in coherent anti-Stokes Raman
      spectroscopic imaging.
AB  - Coherent anti-Stokes Raman scattering (CARS) microscopy is a powerful imaging
      technique that can provide chemical information of organic and nonorganic
      materials through vibrational spectroscopy. However, its contrast is not
      sufficient for monitoring thin film materials. In this study, silica microspheres
      were employed for enhancing the signal contrast in CARS imaging. One layer of
      optically transparent silica microspheres was self-assembled onto polymer grating
      samples to enhance the CARS signals. The highest contrast enhancement factor of
      12.5 was achieved using 6.1-MUm-diameter microspheres. Finite-difference time
      domain method (FDTD) simulation was conducted to simulate the contrast
      enhancement with silica microspheres of different diameters. 

PMID- 24663582
TI  - Field analysis of electro-optic probes for minimally invasive microwave sampling.
AB  - We numerically and experimentally investigate the field invasiveness of microwave
      signals using an electro-optic technique. The distortion of the standing wave
      voltage and pulse waveform probed by the electro-optic technique is explored
      through both minimally invasive external and non-invasive internal sensing
      configurations. First, we analyzed the continuous wave microwave field imaging on
      a millimeter- scale coaxial transmission line using a highly accurate and stable
      electro- optic scanning system. The electric field images from the microwave
      device are attained virtually non-invasively using a miniaturized fiber-coupled
      electro-optic probe. The accuracy of the field imaging associated with various
      probe styles is investigated by numerical analysis and experiment. Then, we
      analyzed the waveform of the coaxial transmission line up to 50 GHz using a
      pulsed electro-optic system with an external probe set. Finally, the invasive
      analysis was extended to the sub-millimeter-scale on-wafer coplanar waveguides,
      where the voltage waveforms are measured using a minimally invasive external
      probe as well as an internal wafer probe for non-invasive sampling. 

PMID- 24663583
TI  - Dynamic symmetry-breaking in a simple quantum model of magneto-electric
      rectification, optical magnetization, and harmonic generation.
AB  - The state mixings necessary to mediate three new optical nonlinearities are shown
      to arise simultaneously and automatically in a 2-level atom with an l = 0 ground
      state and an l = 1 excited state that undergoes a sequence of electric and
      magnetic dipole-allowed transitions. The treatment is based on an extension of
      dressed state theory that includes quantized electric and magnetic field
      interactions. Magneto-electric rectification, transverse magnetization, and
      second-harmonic generation are shown to constitute a family of nonlinear effects
      that can take place regardless of whether inversion is a symmetry of the initial
      unperturbed system or not. Interactions driven jointly by the optical electric
      and magnetic fields produce dynamic symmetry-breaking that accounts for the
      frequency, the intensity dependence, and the polarization of induced
      magnetization in prior experiments. This strong field quantum model explains not
      only how a driven 2-level system may develop nonlinear dipole moments that are
      forbidden between or within its stationary states, but it also broadens the class
      of materials suitable for optical energy conversion applications and magnetic
      field generation with light so as to include all transparent dielectrics. 

PMID- 24663584
TI  - Autocorrelation properties of fully coherent beam with and without orbital
      angular momentum.
AB  - The spatial correlation singularity of a partially coherent vortex beam was
      demonstrated recently [Phys. Rev. Lett. 92, 143905 (2004)], and it was shown that
      the cross-correlation singularity disappears when the spatial coherence is high.
      In this paper, we demonstrate that the spatial autocorrelation function of a
      fully coherent beam in the far-field is equivalent to the Fourier transform of
      its intensity in the source plane. Our theoretical and experimental results show
      that, depending on both the radial and azimuthal mode indices (p, lambda) of the
      incident light beam, the distribution of the far-field autocorrelation function
      displays a series of concentric, alternate bright and dark rings. This phenomenon
      may be used to determine the topological charge (the azimuthal index) of light
      beam with a nonzero radial index. 

PMID- 24663585
TI  - GPU accelerated toolbox for real-time beam-shaping in multimode fibres.
AB  - We present a GPU accelerated toolbox for shaping the light propagation through
      multimode fibre using a spatial light modulator (SLM). The light is modulated
      before being coupled to the proximal end of the fibre in order to achieve
      arbitrary light patterns at the distal end of the fibre. First, the toolbox
      optimises the acquisition time of the transformation matrix of the fibre by
      synchronous operation of CCD and SLM. Second, it uses the acquired transformation
      matrix retained within the GPU memory to design, in real-time, the desired
      holographic mask for on-the-fly modulation of the output light field. We
      demonstrate the functionality of the toolbox by acquiring the transformation
      matrix at the maximum refresh rate of the SLM - 204 Hz, and using it to display
      an on-demand oriented cube, at the distal end of the fibre. The user-controlled
      orientation of the cube and the corresponding holographic mask are obtained in 20
      ms intervals. Deleterious interference effects between the neighbouring points
      are eliminated by incorporating an acousto-optic deflector (AOD) into the system.
      We remark that the usage of the toolbox is not limited to multimode fibres and
      can be readily used to acquire transformation matrix and implement beam-shaping
      in any other linear optical system.

PMID- 24663586
TI  - Nanosecond laser pulse induced concentric surface structures on SiO2 layer.
AB  - We report the periodic concentric surface structures on SiO2 layer induced by a
      single shot nanosecond laser pulse at 1.06 MUm. The fringe period of the
      structures ranges from 7.0 MUm to 26.8 MUm, depending on the laser fluence and
      the distance from central defect precursor. The size and depth of the damage
      sites increase almost linearly with the laser fluence from 19.6 J/cm(2) to 61
      J/cm(2). Plasma flash was clearly observed during the damage process. We
      attribute the formation mechanism of the structures to the interference between
      the reflected laser radiations at the air/shock-front and the shock-front/film
      interfaces.

PMID- 24663587
TI  - Adaptive control of waveguide modes in a two-mode-fiber.
AB  - We experimentally demonstrate an adaptive-optics-based approach that allows
      selective excitation of waveguide modes and their mixtures in a two-mode fiber
      (TMF). A phase-only spatial light modulator is used for wavefront control, using
      feedback signals provided by the correlation between the experimentally measured
      field distribution and the desired mode profiles. Experimental results show the
      optical field within the TMF can be shaped to be pure linearly polarized (LP)
      modes or their combinations. Analysis shows selective mode excitation can be
      achieved using only 5 * 5 independent phase blocks. With proper feedback signals,
      this method should enable one to precisely control the optical field within any
      multimode fiber or other types of waveguides in real time. 

PMID- 24663588
TI  - The origin of interferometric effect involving surface plasmon polariton in
      scattering near-field scanning optical microscopy.
AB  - Scattering near-field scanning optical microscopy (s-NSOM) has been developed to
      characterize optical near field with spatial resolution on the order of 10 nm. In
      this work we report investigation of the interferometric patterns commonly
      occurred in s-NSOM measurements. To reveal the origin of such interference
      patterns, a simple nanoslit is used. Comparing the measured result with a
      simplified analytical model as well as full-field numerical simulations, it is
      shown that the interference pattern is predominantly formed by the in-plane
      component of incidence light and surface plasmon polariton (SPP) launched by the
      nanoslit. This result helps to understand the responses of plasmonic
      nanostructures during s-NSOM measurements. 

PMID- 24663589
TI  - Fluorescence spectral correlation spectroscopy (FSCS) for probes with highly
      overlapping emission spectra.
AB  - We present a fluorescence correlation spectroscopy (FCS) approach to obtain
      spectral cross-talk free auto- and cross-correlation functions for probes with
      highly overlapping emission spectra. Confocal microscopes with either a
      hyperspectral EM-CCD or six-channel PMT array spectral detection were used,
      followed by a photon filtering correlation approach that results in spectral
      unmixing. The method is highly sensitive and can distinguish between Atto488 and
      Oregon Green 488 signals so that auto-correlation curves can be fitted without
      the need for cross-talk correction. We also applied the approach to the membrane
      dye Laurdan whose emission is dependent on the lipid order within the bilayer.
      With fluorescence spectral correlation spectroscopy (FSCS), we could obtain
      spectral cross-talk free auto- and cross-correlation functions corresponding to
      Laurdan located in liquid ordered and liquid disordered phases. 

PMID- 24663590
TI  - Near-infrared active metamaterials and their applications in tunable surface
      enhanced Raman scattering.
AB  - By utilizing the phase change properties of vanadium dioxide (VO2), we have
      demonstrated the tuning of the electric and magnetic modes of split ring
      resonators (SRRs) simultaneously within the near IR range. The electric resonance
      wavelength is blue-shift about 73 nm while the magnetic resonance mode is red
      shifted about 126 nm during the phase transition from insulating to metallic
      phases. Due to the hysteresis phenomenon of VO2 phase transition, both the
      electric and magnetic modes shifts are hysteretic. In addition to the frequency
      shift, the magnetic mode has a trend to vanish due to the fact that the metallic
      phase VO2 has the tendency to short the gap of SRR. We have also demonstrated the
      application of this active metamaterials in tunable surface-enhanced Raman
      scattering (SERS), for a fixed excitation laser wavelength, the Raman intensity
      can be altered significantly by tuning the electric mode frequency of SRR, which
      is accomplished by controlling the phase of VO2 with an accurate temperature
      control.

PMID- 24663591
TI  - XOR and XNOR operations at 12.5 Gb/s using cascaded carrier-depletion microring
      resonators.
AB  - We report the implementation of the XOR and XNOR logical operations using an
      electro-optic circuit, which is fabricated by CMOS-compatible process in the
      silicon-on-insulator (SOI) platform. The circuit consists of two cascaded add
      drop microring resonators (MRRs), which are modulated through electric-field
      induced carrier depletion in reverse biased pn junctions embedded in the ring
      waveguides. The resonance wavelength mismatch between the two nominally identical
      MRRs caused by fabrication errors is compensated by thermal tuning. Simultaneous
      bitwise XOR and XNOR operations of the two electrical modulating signals at the
      speed of 12.5 Gb/s are demonstrated. And 20 Gb/s XOR operation at one output port
      of the circuit is achieved. We explain the phenomena that one half of the
      resonance regions of the device are much more sensitive to the round-trip phase
      shift in the ring waveguides than the other half resonance regions.
      Characteristic graphs with logarithmic phase coordinate are proposed to analyze
      the sensitivity of the demonstrated circuit, as well as several typical
      integrated optical structures. It is found that our circuit with arbitrary chosen
      parameters has similar sensitivity to MRRs under the critical coupling. 

PMID- 24663592
TI  - Overcoming Auger recombination in nanocrystal quantum dot laser using spontaneous
      emission enhancement.
AB  - We propose a method to overcome Auger recombination in nanocrystal quantum dot
      lasers using cavity-enhanced spontaneous emission. We derive a numerical model
      for a laser composed of nanocrystal quantum dots coupled to optical nanocavities
      with small mode-volume. Using this model, we demonstrate that spontaneous
      emission enhancement of the biexciton transition lowers the lasing threshold by
      reducing the effect of Auger recombination. We analyze a photonic crystal
      nanobeam cavity laser as a realistic device structure that implements the
      proposed approach. 

PMID- 24663593
TI  - Fiber optic Fabry-Perot sensor for surface tension analysis.
AB  - We demonstrate a new technique for analyzing surface tension of liquids. This is
      done upon examining the interference signals reflected from a remnant drop
      pending at the cleaved end of a single mode optical fiber. The resulting
      interference patterns are fitted to a multimirror Fabry-Perot model yielding
      information of the drop size. We show that the wetting process of the fiber plays
      an important role in drop formation; in particular, the drop size can be
      correlated to the surface tension of the liquid sample. The proposed
      configuration may render useful for liquids analysis using small sample volume. 

PMID- 24663594
TI  - Surface-coupling of Cerenkov radiation from a modified metallic metamaterial slab
      via Brillouin-band folding.
AB  - Metallic metamaterials with positive dielectric responses are promising as an
      alternative to dielectrics for the generation of Cerenkov radiation [J.-K. So et
      al., Appl. Phys. Lett. 97(15), 151107 (2010)]. We propose here by theoretical
      analysis a mechanism to couple out Cerenkov radiation from the slab surfaces in
      the transverse direction. The proposed method based on Brillouin-zone folding is
      to periodically modify the thickness of the metamaterial slab in the axial
      direction. Moreover, the intensity of the surface-coupled radiation by this
      mechanism shows an order-of-magnitude enhancement compared to that of ordinary
      Smith-Purcell radiation.

PMID- 24663595
TI  - Multistability and spontaneous breaking in pulse-shape symmetry in fiber ring
      cavities.
AB  - We describe the spatio-temporal evolution of ultrashort pulses propagating in a
      fiber ring cavity using an extension of the Lugiato-Lefever model. The model
      predicts the appearance of multistability and spontaneous symmetry breaking in
      temporal pulse shape. We also use a hydrodynamical approach to explain the
      stability of the observed regimes of asymmetry. 

PMID- 24663596
TI  - Engineered surface Bloch waves in graphene-based hyperbolic metamaterials.
AB  - A kind of tunable hyperbolic metamaterial (HMM) based on the graphene-dielectric
      layered structure at near-infrared frequencies is presented, and the engineered
      surface Bloch waves between graphene-based HMM and isotropic medium are
      investigated. Our calculations demonstrate that the frequency and frequency range
      of surface Bloch waves existence can be tuned by varying the Fermi energy of
      graphene sheets via electrostatic biasing. Moreover, we show that the frequency
      range of surface Bloch waves existence can be broadened by decreasing the
      thickness of the dielectric in the graphene-dielectric layered structure or by
      increasing the layer number of graphene sheets. 

PMID- 24663597
TI  - Full-Stokes imaging polarimeter using an array of elliptical polarizer.
AB  - In this paper, a full-Stokes imaging polarimeter operating at 580 nm using an
      array of elliptical polarizers is presented. The division-of-focal-plane
      polarimeter utilizes a set of four optimized measurements which represent a
      regular tetrahedron inscribed in the Poincare sphere. Results from the device
      fabrication, instrument calibration and characterization are presented. The
      performance of the optimized full Stokes polarimeter, as defined by size of the
      standard deviation of the degree of circular polarization, is found to be
      approximately five times better than the performance of the simple full-Stokes
      polarimeter. 

PMID- 24663598
TI  - Asymmetric transmission of terahertz waves using polar dielectrics.
AB  - Asymmetric wave transmission is a Lorentz reciprocal phenomenon, which can appear
      in the structures with broken symmetry. It may enable high forward-to-backward
      transmittance contrast, while transmission for one of the two opposite incidence
      directions is blocked. In this paper, it is demonstrated that ultrawideband, high
      contrast asymmetric wave transmission can be obtained at terahertz frequencies in
      the topologically simple, i.e., one- or two-layer nonsymmetric gratings, which
      are entirely or partially made of a polar dielectric working in the ultralow
      epsilon regime inspired by phonon-photon coupling. A variety of polar dielectrics
      with different characteristics can be used that gives one a big freedom
      concerning design. Simple criteria for estimating possible usefulness of a
      certain polar dielectric are suggested. Contrasts exceeding 80dB can be easily
      achieved without a special parameter adjustment. Stacking a high-epsilon
      corrugated layer with a noncorrugated layer made of a polar dielectric, one can
      enhance transmission in the unidirectional regime. At large and intermediate
      angles of incidence, a better performance can be obtained owing to the common
      effect of nonsymmetric diffractions and directional selectivity, which is
      connected with the dispersion of the ultralow-epsilon material. At normal
      incidence, strong asymmetry in transmission may occur in the studied structures
      as a purely diffraction effect. 

PMID- 24663599
TI  - Supercontinuum generation in hydrogenated amorphous silicon waveguides at
      telecommunication wavelengths.
AB  - We report supercontinuum (SC) generation centered on the telecommunication C-band
      (1550 nm) in CMOS compatible hydrogenated amorphous silicon waveguides. A
      broadening of more than 550 nm is obtained in 1cm long waveguides of different
      widths using as pump picosecond pulses with on chip peak power as low as 4 W. 

PMID- 24663600
TI  - Ultra-sensitive chip-based photonic temperature sensor using ring resonator
      structures.
AB  - Resistance thermometry provides a time-tested method for taking temperature
      measurements. However, fundamental limits to resistance-based approaches has
      produced considerable interest in developing photonic temperature sensors to
      leverage advances in frequency metrology and to achieve greater mechanical and
      environmental stability. Here we show that silicon-based optical ring resonator
      devices can resolve temperature differences of 1 mK using the traditional
      wavelength scanning methodology. An even lower noise floor of 80 MUK for
      measuring temperature difference is achieved in the side-of-fringe, constant
      power mode measurement. 

PMID- 24663601
TI  - Active Fabry-Perot cavity for photonic temporal integrator with ultra-long
      operation time window.
AB  - In this paper, a photonic temporal integrator based on an active Fabry-Perot (F
      P) cavity is proposed and theoretically investigated. The gain medium in the F-P
      cavity is a semiconductor optical amplifier (SOA) with high gain coefficient. Key
      feature of the proposed photonic integrator is that the length of integration
      time window is widely tunable and could be ideally extended to infinitely long
      when the injection current is approaching lasing condition. Based on an F-P
      cavity with practically feasible parameters, a photonic temporal integrator with
      an integration time window of 160 ns and an operation bandwidth of 180 GHz is
      achieved. The time-bandwidth product of this photonic temporal integrator is
      28,800, which is about two-orders of magnitude higher than any previously
      reported results. Gain recovery effect has been also considered and analyzed for
      the impact on performance of the photonic integrator, followed by the simulation
      results of the impact of gain recovery. 

PMID- 24663602
TI  - Study on the productivity of silicon nanoparticles by picosecond laser ablation
      in water: towards gram per hour yield.
AB  - An investigation on the productivity of silicon nanoparticles by picosecond laser
      ablation in water is presented. A systematic experimental study is performed as
      function of the laser wavelength, fluence and ablation time. In case of ablation
      at 1064 nm silicon nanoparticles with a mean diameter of 40 nm are produced.
      Instead, ablation at 355 nm results in nanoparticles with a mean diameter of 9 nm
      for short ablation time while the mean diameter decreases to 3 nm at longer
      ablation time. An original model based on the in-situ ablation/photo
      fragmentation physical process is developed, and it very well explains the
      experimental productivity findings. The reported phenomenological model has a
      general validity, and it can be applied to analyze pulsed laser ablation in
      liquid in order to optimize the process parameters for higher productivity.
      Finally, an outlook is given towards gram per hour yield of ultra-small silicon
      nanoparticles. 

PMID- 24663603
TI  - An efficient simulation and analysis method of moire patterns in display systems.
AB  - A precise and fast computational method for the simulation and analysis of moire
      patterns is proposed. This new algorithm is based on convolution with
      superposition of the intensity profile which is transmitted from the optical
      layers and the point spread function. The computational time is shown to be much
      faster than that of the ray-tracing algorithm because the new algorithm does not
      involve a massive calculation. Also, information on the moire pitch can be
      extracted directly from the sampling data of the moire patterns. 

PMID- 24663604
TI  - High order kinoforms as a broadband achromatic diffractive optics for terahertz
      beams.
AB  - We discuss thin optical structures that allow chromatic aberrations to be avoided
      in the THz domain. The paper contains the theoretical considerations, computer
      modeling and experimental evaluation of the high order kinoform diffractive
      elements in the THz range. According to the obtained results application of the
      high order kinoforms enables broadband operation in the THz range. 

PMID- 24663605
TI  - Dimensional variation tolerant silicon-on-insulator directional couplers.
AB  - We design silicon ridge/rib waveguide directional couplers which are
      simultaneously tolerant to width, height, coupling gap, and etch depth
      variations. Using wafer-scale measurements of structures fabricated in the IMEC
      Standard Passives process, we demonstrate the normalized standard deviation in
      the per-length coupling coefficient (a metric for the splitting ratio variation)
      of the variation-tolerant directional couplers is up to 4 times smaller than that
      of strip waveguide designs. The variation-tolerant couplers are also the most
      broadband and the deviation in the coupling coefficient shows the lowest spectral
      dependence. 

PMID- 24663606
TI  - Generation of an air laser at extended distances by femtosecond laser
      filamentation with telescope optics.
AB  - We present the generation of self-induced-white-light-seeded lasing action of
      nitrogen molecules in air by a Ti:sapphire femtosecond laser (800 nm, 5.5 mJ) and
      demonstrate that such lasing action is strongly influenced by external focusing
      conditions. It is found that the self-seeded lasing signal of N(2)(+) at ~391 nm
      decreases dramatically by orders of magnitude and ultimately disappears when the
      focal length of an external lens increases from 0.5 m to 1 m. By using a
      telescope, it is shown that such limitation can be overcome and the 391 nm lasing
      can be controlled to occur at remotely designated distance, providing a
      possibility for practical applications in standoff spectroscopy.

PMID- 24663607
TI  - Performance evaluation of large-scale multi-stage hetero-granular optical cross
      connects.
AB  - We proposed generalized large-scale two-stage-routing OXC architectures and
      evaluated the performance possible with the use of small-degree WSSs and simple
      optical devices; 1 x n switches or WBSSs. Numerical evaluations verify that the
      new architectures reduce necessary hardware scale substantially at the cost of
      few additional fibers while their effectiveness increases with the traffic
      demand. The tradeoff between the link resource increase and the hardware scale
      reduction is also clarified.

PMID- 24663608
TI  - A novel elastic optical path network that utilizes bitrate-specific anchored
      frequency slot arrangement.
AB  - We propose a novel elastic optical path network where each specific bitrate
      signal uses its own dedicated fixed grid and one edge of its frequency grid is
      anchored at a specific frequency. Numerical evaluations using various bitrate
      signal patterns and network topologies show that the network proposal can almost
      match the performance of conventional flexible grid networks, while greatly
      mitigating the hardware requirements: it allows the use of the tunable filters
      for the fixed grid systems. 

PMID- 24663609
TI  - Propagation of a topologically half-charge vortex light beam in a self-focusing
      photorefractive medium.
AB  - While a fundamental Gaussian light beam can form stably a spatial soliton in
      certain self-focusing medium, a single-wave topologically integer-n-charge vortex
      light beam cannot. It breaks up into 2n filaments due to symmetry breaking and
      azimuthal instability, in which every azimuthal section of a pi phase range from
      a soliton and repels itself from its azimuthal neighboring soliton. Then what
      happens to the half-charge vortex light beam, which contains only one section of
      a pi phase range? We investigate experimentally and theoretically the propagation
      and stability of a topologically half-charge vortex light beam in a self-focusing
      photorefractive medium. We observed that the light beam propagates unstably in a
      self-focusing medium and breaks up into three filaments. This result is confirmed
      by numerical simulation and perturbation analysis. 

PMID- 24663610
TI  - Local plasmon resonances of metal-in-metal core-shells.
AB  - We investigate the tunability and strength of the localized surface plasmons of
      binary metal-in-metal core-shells. Ellipsoids are used as an analytical model to
      show how the fill factor continuously tunes a hybridized mode between those of
      the constituents, suggesting the use of metal combinations with widely differing
      plasma frequencies for broad tunability. A quasistatic eigenmode method is used
      separate geometric and material parameters to facilitate prediction of hybridized
      dipole modes in arbitrary shapes. A modified ellipsoid model is found to
      adequately describe the symmetric dipole-dipole resonance of well-rounded
      cuboids. 

PMID- 24663611
TI  - Interaction between meta-materials and shallow donors in bulk GaN at THz
      frequency.
AB  - We report the coupling and interaction between shallow donors and microcavities
      in bulk GaN at THz frequencies. At 4K, the shallow donors lead to an absorption
      at 23.5 meV (5.7 THz) under optical pumping above the bandgap of GaN. The
      microcavities are based on metamaterials and are designed to resonate around 5.7
      THz. At 4 K, the matter-cavity interaction is clearly demonstrated on
      differential transmission of the sample. The cavity resonance shifts when the
      absorption occurs. Our model and simulations are in good agreement with the
      experimental data. 

PMID- 24663612
TI  - Experimental characterization and mitigation of turbulence induced signal fades
      within an ad hoc FSO network.
AB  - Optical beams propagating through the turbulent atmospheric channel suffer from
      both the attenuation and phase distortion. Since future wireless networks are
      envisaged to be deployed in the ad hoc mesh topology, this paper presents the
      experimental laboratory characterization of mitigation of turbulence induced
      signal fades for two ad hoc scenarios. Results from measurements of the thermal
      structure constant along the propagation channels, changes of the coherence
      lengths for different turbulence regimes and the eye diagrams for partially
      correlated turbulences in free space optical channels are discussed. Based on
      these results future deployment of optical ad hoc networks can be more
      straightforwardly planned. 

PMID- 24663613
TI  - Electromagnetically induced transparency-like effect in a two-bus waveguides
      coupled microdisk resonator.
AB  - We observe theoretically and experimentally electromagnetically induced
      transparency (EIT)-like effect in a single microdisk resonator (MDR) evanescently
      coupled with two bus waveguides. This structure is modeled using transfer matrix
      method, and it is revealed that the EIT-like spectrum originates from the
      coherent interference between two nearby low-order whispering-gallery modes
      (WGMs) with comparable quality factors. The EIT-like properties have been
      investigated analytically with respect to coupling efficiency, round-trip power
      attenuation, as well as phase spacing between two resonances. The resonance
      spacing and mode coupling are adjustable by varying the effective indices of WGMs
      and waveguide mode. Consequently, fully integrated MDRs were fabricated in
      silicon. Resonant modes and coupling efficiency are studied in one-bus waveguide
      coupled MDRs. Finally, EIT-like resonance is observed in a two-bus waveguides
      coupled MDR of 3 MUm in radius with a quality factor of 4,200 and central
      transmission larger than 0.65. The experimental results agree with our modeling
      well and show good internal consistency, confirming that two WGMs coupled in a
      point-to-point manner are required for EIT-like effect. 

PMID- 24663614
TI  - Formation of self-trapping waveguides in bulk PMMA media doped with
      Phenanthrenequinone.
AB  - Experimental and theoretical investigations of light self-trapping waveguides in
      a bulk polymeric medium based on polymethylmethacrylate (PMMA) with
      photosensitive phenanthrenequinone (PQ)-molecules are examined. Self-channeling
      was generated for the first time in this nonlinear bulk PQ-PMMA media with a
      thickness up to several millimeters and 0.1 mol. % PQ-concentration. The
      experimental formation of volume waveguide structures with a length of 2 - 3 cm
      at different laser wavelengths (405 nm, 488 nm, and 514.5 nm) was demonstrated.
      The calculations based on a model for the laser beam propagation in the bulk PQ
      PMMA medium with competitive nonlinearities are in a good agreement with the
      experiments. 

PMID- 24663615
TI  - Fluence and polarisation dependence of GaAs based Lateral Photo-Dember terahertz
      emitters.
AB  - We characterise THz output of lateral photo-Dember (LPD) emitters based on semi
      insulating (SI), unannealed and annealed low temperature grown (LTG) GaAs.
      Saturation of THz pulse power with optical fluence is observed, with unannealed
      LTG GaAs showing highest saturation fluence at 1.1 +/- 0.1 mJ cm(-2). SI-GaAs LPD
      emitters show a flip in signal polarity with optical fluence that is attributed
      to THz emission from the metal-semiconductor contact. Variation in optical
      polarisation affects THz pulse power that is attributed to a local optical
      excitation near the metal contact.

PMID- 24663616
TI  - Third-order antibunching from an imperfect single-photon source.
AB  - We measure second- and third-order temporal coherences, g((2))(tau) and
      g((3))(tau1,tau2), of an optically excited single-photon source: an InGaAs
      quantum dot in a microcavity pedestal. Increasing the optical excitation power
      leads to an increase in the measured count rate, and also an increase in multi
      photon emission probability. We show that standard measurements of g((2)) provide
      limited information about this multi-photon probability, and that more
      information can be gained by simultaneously measuring g((3)). Experimental
      results are compared with a simple theoretical model to show that the observed
      antibunchings are consistent with an incoherent addition of two sources: 1) an
      ideal single-photon source that never emits multiple photons and 2) a background
      cavity emission having Poissonian photon number statistics. Spectrally resolved
      cross-correlation measurements between quantum-dot and cavity modes show that
      photons from these two sources are largely uncorrelated, further supporting the
      model. We also analyze the Hanbury Brown-Twiss interferometer implemented with
      two or three "click" detectors, and explore the conditions under which it can be
      used to accurately measure g((2))(tau) and g((3))(tau1,tau2).

PMID- 24663617
TI  - Selective generation of ultracold high-density 1s orthoexcitons in Cu2O with
      phase-modulated pulse using acousto-optic programmable filter.
AB  - Ultracold and high-density 1s orthoexcitons in semiconductor cuprous oxide are
      prepared via resonant two-photon absorption of a phase-tailored femtosecond
      pulse, by utilizing an acousto-optic programmable dispersive filter. The
      stability of the quantum degenerate exciton gas is studied using excitonic Lyman
      spectroscopy. A density of 10(16) cm(-3) is realized without creating hot
      carriers, and the Lyman spectrum remains unchanged at this density. This result
      assures the stability of a spontaneous Bose-Einstein condensate of excitons at
      sub-Kelvin temperatures.

PMID- 24663618
TI  - Ultrasensitive silicon photonic-crystal nanobeam electro-optical modulator:
      design and simulation.
AB  - Design and simulation results are presented for an ultralow switching energy,
      resonator based, silicon-on-insulator (SOI) electro-optical modulator. The
      nanowire waveguide and Q ~8500 resonator are seamlessly integrated via a high
      transmission tapered 1D photonic crystal cavity waveguide structure. A lateral p
      n junction of modulation length L(m) ~lambda is used to alter the index of
      refraction and, therefore, shift the resonance wavelength via fast carrier
      depletion. Differential signaling of the device with DeltaV ~0.6 Volts allows for
      a 6 dB extinction ratio at telecom wavelengths with an energy cost as low as 14
      attojoules/bit.

PMID- 24663619
TI  - Three-dimensional analysis of optical forces generated by an active tractor beam
      using radial polarization.
AB  - We theoretically study the three-dimensional behavior of nanoparticles in an
      active optical conveyor. To do this, we solved the Langevin equation when the
      forces are generated by a focusing system at the near field. Analytical
      expressions for the optical forces generated by the optical conveyor were
      obtained by solving the Richards and Wolf vectorial diffraction integrals in an
      approximated form when a mask of two annular pupils is illuminated by a radially
      polarized Hermite-Gauss beam. Trajectories, in both the transverse plane and the
      longitudinal direction, are analyzed showing that the behavior of the optical
      conveyor can be optimized by conveniently choosing the configuration of the mask
      of the two annular pupils (inner and outer radius of the two rings) in order to
      trap and transport all particles at the focal plane. 

PMID- 24663620
TI  - Sensitivity enhancement through overlapping simultaneously excited Fano resonance
      modes of metallic-photonic-crystal sensors.
AB  - We investigated enhancement of sensitivity of sensors based on metallic photonic
      crystals through tuning the thickness of the waveguide layer by pulsed laser
      deposition. Thicker waveguides made of InGaZnO allow double resonance of Fano
      coupling modes due to plasmonic-photonic interactions. Tuning the angle of
      incidence enables overlap between these doubly resonant modes, which induces much
      enlarged and spectrally narrowed sensor signals, leading to significantly
      enhanced sensitivity of the sensor device. The thickness of the waveguide layer
      is found to be a crucial structural parameter to improve sensitivity of the MPC
      sensors. 

PMID- 24663621
TI  - Generation of achromatic, uniform-phase, radially polarized beams.
AB  - Axially symmetric half-wave plates have been used to generate radially polarized
      beams that have constant phase in the plane transverse to propagation. However,
      since the retardance introduced by these waveplates depends on the wavelength, it
      is difficult to generate radially polarized beams achromatically. This paper
      describes a technique suitable for the generation of achromatic, radially
      polarized beams with uniform phase. The generation system contains, among other
      optical components, an achromatic, axially symmetric quarter-wave plate based on
      total internal reflection. For an incident beam with a constant phase
      distribution, the system generates a beam with an extra geometrical phase term.
      To generate a beam with the correct phase distribution, it is therefore necessary
      to have an incident optical vortex with an azimuthally varying phase distribution
      of the form exp( + itheta). We show theoretically that the phase component of
      radially polarized beam is canceled out by the phase component of the incident
      optical vortex, resulting in a radially polarized beam with uniform phase.
      Additionally, we present an experimental setup able to generate the achromatic,
      uniform-phase, radially polarized beam and experimental results that confirm that
      the generated beam has the correct phase distribution. 

PMID- 24663622
TI  - Liquid crystal-based square lens array with tunable focal length.
AB  - We demonstrate a liquid crystal (LC)-based square lens array with two focusing
      modes according to the polarization state of the input light. The homogeneously
      aligned LC layer is placed on an array of static square lenses fabricated using a
      photo-curable polymer whose refractive index is matched with the refractive index
      of the LC. For the input beam polarized parallel to the easy axis of the LC, the
      focal length is varied with the applied voltage from a few meters to 21 mm which
      corresponds to the focal length of the static lens. For the perpendicularly
      polarized input beam, the focal length is independent of the applied voltage and
      remains constant. The two focusing effects with high optical performance over
      fully activated areas are useful for polarization-dependent imaging systems and
      three-dimensional displays in projection and integral imaging. 

PMID- 24663623
TI  - Highly efficient picosecond diamond Raman laser at 1240 and 1485 nm.
AB  - We present a highly efficient picosecond diamond Raman laser synchronously-pumped
      by a 4.8 W mode-locked laser at 1064 nm. A ring cavity was adopted for efficient
      operation. With a low-Q cavity for first-Stokes 1240 nm, we have achieved 2.75 W
      output power at 1240 nm with 59% overall conversion efficiency. The slope
      efficiency tended towards 76% far above the SRS threshold, approaching the SRS
      quantum limit for diamond. A high-Q first-Stokes cavity was employed for second
      Stokes 1485 nm generation through the combined processes of four-wave mixing and
      single-pass stimulated Raman scattering. Up to 1.0 W of second-stokes at 1485 nm
      was obtained, corresponding to 21% overall conversion efficiency. The minimum
      output pulse duration was compressed relative to the 15 ps pump, producing pulses
      as short as 9 ps for 1240 nm and 6 ps for 1485 nm respectively. 

PMID- 24663624
TI  - High-temperature, continuous-wave operation of terahertz quantum-cascade lasers
      with metal-metal waveguides and third-order distributed feedback.
AB  - Currently, different competing waveguide and resonator concepts exist for
      terahertz quantum-cascade lasers (THz QCLs). We examine the continuous-wave (cw)
      performance of THz QCLs with single-plasmon (SP) and metal-metal (MM) waveguides
      fabricated from the same wafer. While SP QCLs are superior in terms of output
      power, the maximum operating temperature for MM QCLs is typically much higher.
      For SP QCLs, we observed cw operation up to 73 K as compared to 129 K for narrow
      (<= 15 MUm) MM QCLs. In the latter case, single-mode operation and a narrow beam
      profile were achieved by applying third-order distributed-feedback gratings and
      contact pads which are optically insulated from the intended resonators. We
      present a quantitative analytic model for the beam profile, which is based on
      experimentally accessible parameters. 

PMID- 24663626
TI  - Laser parallel nanofabrication by single femtosecond pulse near-field ablation
      using photoresist masks.
AB  - A new near-field processing method by femtosecond laser ablation using
      photoresist enhancing masks is numerically and experimentally investigated.
      Periodical structures with 2 MUm pitch, 1 MUm width and 300 nm height, created in
      polymethyl methacrylate photoresist by e-beam lithography, were used to intensify
      the incident laser radiation. The near-field distribution and the intensification
      factor of the optical radiation were computed using the Finite-Difference-Time
      Domain numerical simulations. The pattern of the photoresist mask was imprinted
      on the surface of a silicon wafer. Using a single infrared femtosecond laser
      pulse, uniform and continuum grooves with the width in the range of 250 nm were
      obtained on large silicon surface. 

PMID- 24663625
TI  - Direct rapid-prototyping fabrication of computer-generated volume holograms in
      the millimeter-wave and terahertz regime.
AB  - Computer-generated volume holograms (CGVHs) are gradient refractive index (GRIN)
      devices that consist of a superposition of multiple periodic diffraction
      gratings. Fabrication of these components for the visible range is difficult due
      to the small length-scale requirements but is more tenable in the terahertz
      (THz), as the length scales become more practical (>= 10<sup>-5</sup> m). We
      successfully utilized polymer-based 3D additive rapid-prototyping technology to
      fabricate, to our knowledge, the world's first 3D THz CGVH in approximately 50
      minutes, using $12 of consumables. This demonstration suggests that this
      technique could be extended to fabricate THz volumetric optics with arbitrary
      electromagnetic profiles. 

PMID- 24663627
TI  - Design of freeform imaging systems with linear field-of-view using a construction
      and iteration process.
AB  - In this paper, a design method based on a construction and iteration process is
      proposed for designing freeform imaging systems with linear field-of-view (FOV).
      The surface contours of the desired freeform surfaces in the tangential plane are
      firstly designed to control the tangential rays of multiple field angles and
      different pupil coordinates. Then, the image quality is improved with an
      iterative process. The design result can be taken as a good starting point for
      further optimization. A freeform off-axis scanning system is designed as an
      example of the proposed method. The convergence ability of the construction and
      iteration process to design a freeform system from initial planes is validated.
      The MTF of the design result is close to the diffraction limit and the scanning
      error is less than 1 MUm. This result proves that good image quality and scanning
      linearity were achieved.

PMID- 24663628
TI  - Crosstalk reduction in stereoscopic 3D displays: disparity adjustment using
      crosstalk visibility index for crosstalk cancellation.
AB  - Stereoscopic displays provide viewers with a truly fascinating viewing
      experience. However, current stereoscopic displays suffer from crosstalk that is
      detrimental to image quality, depth quality, and visual comfort. In order to
      reduce the perceived crosstalk in stereoscopic displays, this paper proposes a
      crosstalk reduction method that combines disparity adjustment and crosstalk
      cancellation. The main idea of the proposed method is to displace the visible
      crosstalk using the disparity adjustment in a way that less amounts of intensity
      leakage occur on perceptually important regions in a scene. To this purpose, we
      estimate a crosstalk visibility index map for the scene that represents pixel-by
      pixel importance values associated with the amount of perceived crosstalk and
      negative-after-effects of the crosstalk cancellation. Based on the crosstalk
      visibility index, we introduce a new disparity adjustment method that reduces the
      annoying crosstalk in processed images, which is followed by the crosstalk
      cancellation. The effectiveness of the proposed method has been successfully
      evaluated by subjective assessments of image quality and viewing preference.
      Experimental results demonstrate that the proposed method effectively improves
      the image quality and overall viewing quality of stereoscopic videos. 

PMID- 24663629
TI  - Model laser damage precursors for high quality optical materials.
AB  - Surface damage is known to occur at fluences well below the intrinsic limit of
      the fused silica. A native surface precursor can absorb sub band-gap light and
      initiate a process which leads to catastrophic damage many micrometers deep with
      prominent fracture networks. Previously, the absorption front model of damage
      initiation has been proposed to explain how this nano-scale absorption can lead
      to macro-scale damage. However, model precursor systems designed to study
      initiation experimentally have not been able to clearly reproduce these damage
      events. In our study, we create artificial absorbers on fused silica substrates
      to investigate precursor properties critical for native surface damage
      initiation. Thin optically absorbing films of different materials were deposited
      on silica surfaces and then damage tested and characterized. We demonstrated that
      strong interfacial adhesion strength between absorbers and silica is crucial for
      the launch of an absorption front and subsequent damage initiation. Simulations
      using the absorption-front model are performed and agree qualitatively with
      experimental results. 

PMID- 24663630
TI  - Imaging blood cells through scattering biological tissue using speckle scanning
      microscopy.
AB  - We demonstrate imaging of blood cells enclosed in chicken skin tissue using
      speckle scanning microscopy (SSM). Clear images of multiple cells were obtained
      with subcellular resolution and good image fidelity, provided that the object
      dimension was smaller than the maximum scanning range of the speckle pattern.
      These results point to the potential and the challenges of using SSM technique
      for biological imaging. 

PMID- 24663632
TI  - Experimental demonstration of a reconfigurable silicon thermo-optical device
      based on spectral tuning of ring resonators for optical signal processing.
AB  - We have experimentally demonstrated a reconfigurable silicon thermo-optical
      device able to tailor its intrinsic spectral optical response by means of the
      thermo-optical control of individual and uncoupled resonant modes of micro-ring
      resonators. Preliminarily results show that the device's optical response can be
      tailored to build up distinct and reconfigurable logic levels for optical signal
      processing, as well as control of overall figures of merit, such as free-spectral
      range, extinction ratio and 3 dB bandwidth. In addition, the micro-heaters on top
      of the ring resonators are able to tune the resonant wavelength with efficiency
      of 0.25 nm/mW within a range of up to 10 nm, as well as able to switch the
      resonant wavelength within fall and rise time of 15 MUs.

PMID- 24663631
TI  - A rapid, dispersion-based wavelength-stepped and wavelength-swept laser for
      optical coherence tomography.
AB  - Optical-domain subsampling enables Fourier-domain OCT imaging at high-speeds and
      extended depth ranges while limiting the required acquisition bandwidth. To
      perform optical-domain subsampling, a wavelength-stepped rather than a wavelength
      swept source is required. This preliminary study introduces a novel design for a
      rapid wavelength-stepped laser source that uses dispersive fibers in combination
      with a fast lithium-niobate modulator to achieve wavelength selection. A laser
      with 200 GHz wavelength-stepping and a sweep rate of 9 MHz over a 94 nm range at
      a center wavelength of 1550 nm is demonstrated. A reconfiguration of this source
      design to a continuous wavelength-swept light for conventional Fourier-domain OCT
      is also demonstrated. 

PMID- 24663633
TI  - Nanoscale topography and spatial light modulator characterization using wide
      field quantitative phase imaging.
AB  - We demonstrate an optical technique for large field of view quantitative phase
      imaging of reflective samples. It relies on a common-path interferometric design,
      which ensures high stability without the need for active stabilization. The
      technique provides single-shot, full-field and robust measurement of nanoscale
      topography of large samples. Further, the inherent stability allows reliable
      measurement of the temporally varying phase retardation of the liquid crystal
      cells, and thus enables real-time characterization of spatial light modulators.
      The technique's application potential is validated through experimental results. 

PMID- 24663634
TI  - Coupling of THz radiation with intervalence band transitions in microcavities.
AB  - The strong coupling of THz radiation and material excitations can improve the
      quantum efficiency of THz emitters. In this paper, we investigate THz polaritons
      and antipolaritons based on valence band transitions, which allow TE coupling in
      a simple configuration. The approach can improve the quantum efficiency of THz
      based devices based on TE mode in the strong coupling regime of THz radiations
      and intervalence bands transitions in a GaAs/AlGaAs quantum wells. A
      Nonequilibrium Many Body Approach for the optical response beyond the Hartree
      Fock approximation is used as input to the effective dielectric function
      formalism for the polariton/antipolariton problem. The energy dispersion
      relations in the THz range are obtained by adjusting the full numerical solutions
      to simple analytical expressions, which can be used for non specialists in a wide
      number of new structures and material systems. The combination of manybody and
      nonparabolicity at high densities leads to dramatic changes in the polariton
      spectra in a nonequilibrium configuration, which is only possible for
      intervalence band transitions. 

PMID- 24663635
TI  - Laser induced spark ignition of coaxial methane/oxygen/nitrogen diffusion flames.
AB  - We report the laser induced spark ignition (LSI) of coaxial
      methane/oxygen/nitrogen diffusion flames using the 1064 nm output of a Q-switched
      Nd:YAG laser. The minimum ignition energy (MIE) and ignition time of the LSI has
      been determined by measuring the emission signals due to the ignited flames. The
      effects of the gas mixture properties, including the overall equivalence ratio
      (F), oxygen concentration and flow rate, and the ignition positions on the two
      parameters have been investigated systematically. The variation of the MIE and
      ignition time with the experimental conditions has been compared with the
      existing results and discussed with a special concentration on the effects of the
      local F. 

PMID- 24663636
TI  - Measuring color differences in automotive samples with lightness flop: a test of
      the AUDI2000 color-difference formula.
AB  - From a set of gonioapparent automotive samples from different manufacturers we
      selected 28 low-chroma color pairs with relatively small color differences
      predominantly in lightness. These color pairs were visually assessed with a gray
      scale at six different viewing angles by a panel of 10 observers. Using the
      Standardized Residual Sum of Squares (STRESS) index, the results of our visual
      experiment were tested against predictions made by 12 modern color-difference
      formulas. From a weighted STRESS index accounting for the uncertainty in visual
      assessments, the best prediction of our whole experiment was achieved using
      AUDI2000, CAM02-SCD, CAM02-UCS and OSA-GP-Euclidean color-difference formulas,
      which were no statistically significant different among them. A two-step
      optimization of the original AUDI2000 color-difference formula resulted in a
      modified AUDI2000 formula which performed both, significantly better than the
      original formula and below the experimental inter-observer variability.
      Nevertheless the proposal of a new revised AUDI2000 color-difference formula
      requires additional experimental data. 

PMID- 24663637
TI  - A multiple-input-multiple-output visible light communication system based on
      VCSELs and spatial light modulators.
AB  - A multiple-input-multiple-output (MIMO) visible light communication (VLC) system
      employing vertical cavity surface emitting laser (VCSEL) and spatial light
      modulators (SLMs) with 16-quadrature amplitude modulation (QAM)-orthogonal
      frequency-division multiplexing (OFDM) modulating signal is proposed and
      experimentally demonstrated. The transmission capacity of system is significantly
      increased by space-division demultiplexing scheme. With the assistance of low
      noise amplifier (LNA) and data comparator, good bit error rate (BER) performance,
      clear constellation map, and clear eye diagram are achieved for each optical
      channel. Such a MIMO VLC system would be attractive for providing services
      including data and telecommunication services. Our proposed system is suitably
      applicable to the lightwave communication system in wireless transmission. 

PMID- 24663639
TI  - Accelerating light beams with arbitrarily transverse shapes.
AB  - Accelerating beams are wave packets that preserve their shape while propagating
      along curved trajectories. Their unique characteristics have opened the door to
      applications that range from optical micromanipulation and plasma-channel
      generation to laser micromachining. Here, we demonstrate, theoretically and
      experimentally, that accelerating beams can be generated with a variety of
      arbitrarily chosen transverse shapes. We present a general method to construct
      such beams in the paraxial and nonparaxial regime and demonstrate experimentally
      their propagation in the paraxial case. The key ingredient of our method is the
      use of the spectral representation of the accelerating beams, which offers a
      unique and compact description of these beams. The on-demand accelerating light
      patterns described here are likely to give rise to new applications and add
      versatility to the current ones. 

PMID- 24663638
TI  - Superconducting series nanowire detector counting up to twelve photons.
AB  - We demonstrate a superconducting photon-number-resolving detector capable of
      resolving up to twelve photons at telecommunication wavelengths. It is based on a
      series array of twelve superconducting NbN nanowire elements, each connected in
      parallel with an integrated resistor. The photon-induced voltage signals from the
      twelve elements are summed up into a single readout pulse with a height
      proportional to the detected photon number. Thirteen distinct output levels
      corresponding to the detection of n = 0-12 photons are observed experimentally. A
      detailed analysis of the linearity and of the excess noise shows the potential of
      scaling to an even larger dynamic range. 

PMID- 24663640
TI  - Coherent all-optical control of ultracold atoms arrays in permanent magnetic
      traps.
AB  - We propose a hybrid architecture for quantum information processing based on
      magnetically trapped ultracold atoms coupled via optical fields. The ultracold
      atoms, which can be either Bose-Einstein condensates or ensembles, are trapped in
      permanent magnetic traps and are placed in microcavities, connected by silica
      based waveguides on an atom chip structure. At each trapping center, the
      ultracold atoms form spin coherent states, serving as a quantum memory. An all
      optical scheme is used to initialize, measure and perform a universal set of
      quantum gates on the single and two spin-coherent states where entanglement can
      be generated addressably between spatially separated trapped ultracold atoms.
      This allows for universal quantum operations on the spin coherent state quantum
      memories. We give detailed derivations of the composite cavity system mediated by
      a silica waveguide as well as the control scheme. Estimates for the necessary
      experimental conditions for a working hybrid device are given. 

PMID- 24663641
TI  - Conformal dome aberration correction with gradient index optical elements.
AB  - A conformal dome optical system was established and aberration characteristics of
      the dome were investigated using Zernike aberration theory. The conformal dome
      was designed with gradient index element. The designing method was introduced and
      the optimizing results were analyzed in detail. The results show that the Zernike
      aberrations produced by the conformal dome decreased dramatically. Also, a
      complete conformal optical system was designed to further illustrate the
      aberration correction effect of gradient index elements. The results show that
      the utilization of gradient index optical elements not only improves the imaging
      quality, but also simplifies the structure of the conformal optical system. 

PMID- 24663642
TI  - Comparison of electromagnetically induced transparency between silver, gold, and
      aluminum metamaterials at visible wavelengths.
AB  - Electromagnetically induced transparency (EIT)-like effects in silver, gold, and
      aluminum metamaterials consisting of dipole resonators and quadrupole resonators
      were demonstrated at visible wavelengths. Optical characteristics of the
      metamaterials could be controlled by the gap distance between the two resonators.
      EIT-like effects were observed at wavelengths between 603 and 789 nm, 654 and 834
      nm, and 462 and 693 nm for the silver, gold, and aluminum EIT metamaterials,
      respectively. At wavelengths longer than around 650 nm, the silver metamaterials
      had better EIT-like features. At wavelengths shorter than around 650 nm, on the
      other hand, the aluminum metamaterials showed promising EIT-like results. 

PMID- 24663643
TI  - Absolute flatness measurement using oblique incidence setup and an iterative
      algorithm. A demonstration on synthetic data.
AB  - A method to provide absolute planarity measurements through an interferometric
      oblique incidence setup and an iterative algorithm is presented. With only three
      measurements, the calibration of absolute planarity is achieved in a fast and
      effective manner. Demonstration with synthetic data is provided, and the possible
      application to very long flat mirrors is pointed out. 

PMID- 24663644
TI  - Speckle noise reduction on a laser projection display via a broadband green light
      source.
AB  - A broadband green light source was demonstrated using a tandem-poled lithium
      niobate (TPLN) crystal. The measured wavelength and temperature bandwidth were
      6.5 nm and 100  degrees C, respectively, spectral bandwidth was 36 times broader
      than the periodically poled case. Although the conversion efficiency was smaller
      than in the periodic case, the TPLN device had a good figure of merit owing to
      the extremely large bandwidth for wavelength and temperature. The developed
      broadband green light source exhibited speckle noise approximately one-seventh of
      that in the conventional approach for a laser projection display.

PMID- 24663645
TI  - A two-in-one Faraday rotator mirror exempt of active optical alignment.
AB  - A two-in-one Faraday rotator mirror was presented, which functions as two
      independent Faraday rotation mirrors with a single device. With the introduction
      of a reflection lens as substitution of the mirror in traditional structure, this
      device is characterized by exemption of active optical alignment for the
      designers and manufacturers of Faraday rotator mirrors. A sample was fabricated
      by passive mechanical assembly. The insertion loss was measured as 0.46 dB/0.50
      dB for the two independent ports, respectively.

PMID- 24663646
TI  - Towards acousto-optic tissue imaging with nanosecond laser pulses.
AB  - We present a way to generate acousto-optical signals in timovssue-like media with
      nanosecond laser pulses. Our method is based on recording and analyzing speckle
      patterns formed by interaction of nanosecond laser pulses with tissue, without
      and with simultaneous application of ultrasound. Stroboscopic application allows
      visualizing the temporal behavior of speckles while the ultrasound is propagating
      through the medium. We investigate two ways of quantifying the acousto-optic
      effect, viz. adding and subtracting speckle patterns obtained at various
      ultrasound phases. Both methods are compared with the existing speckle contrast
      method using a 2D scan and are found to perform similarly. Our method gives
      outlook on overcoming the speckle decorrelation problem in acousto-optics, and
      therefore brings in-vivo acousto-optic measurements one step closer. Furthermore
      it enables combining acousto-optics and photoacoustics in one setup with a single
      laser. 

PMID- 24663647
TI  - Guided continuous-wave and graphene-based Q-switched lasers in carbon ion
      irradiated Nd:YAG ceramic channel waveguide.
AB  - We demonstrate the lasing performance in the Nd:YAG ceramic channel waveguide
      produced by the carbon ion irradiation, including the continuous-wave (cw) and
      graphene Q-switched configurations. The highest slope efficiency of 56% and the
      lowest threshold of 40 mW have been obtained for the cw waveguide laser. With
      graphene as a saturable absorber, the Q-switched laser produces stable pulses
      with 57 ns pulse duration and 77 nJ pulse energy, respectively. Under the
      variation of the pumping power, the repetition of the pulse laser could be
      modified from 1.5 MHz to 4.1 MHz. 

PMID- 24663648
TI  - Highly sensitive force sensor based on optical microfiber asymmetrical Fabry
      Perot interferometer.
AB  - An asymmetrical Fabry-Perot interferometric (AFPI) force sensor is fabricated
      based on a narrowband reflection of low-reflectivity fiber Bragg grating (LR-FBG)
      and a broadband Fresnel reflection of the cleaved fiber end. The AFPI sensor
      includes a section of microfiber made by tapering and it achieves a force
      sensitivity of 0.221 pm/MUN with a tapered microfiber of 40 mm length and 6.1 MUm
      waist diameter. Compared with similar AFPI structure in 125 MUm-diameter single
      mode fiber, the force sensitivity of the microfiber AFPI structure is greatly
      enhanced due to its smaller diameter and can be optimized for different force
      scales by controlling the diameter. The fabrication process of the AFPI sensor is
      simple and cost-effective. The AFPI sensor has better multiplexing capacity than
      conventional extrinsic fiber-optic Fabry-Perot sensors, while it also release the
      requirement on the wavelength matching of the FBG-pair-based FPI.

PMID- 24663649
TI  - Growth of low-defect-density nonpolar a-plane GaN on r-plane sapphire using pulse
      NH3 interrupted etching.
AB  - Nonpolar a-plane (11-20) GaN (a-GaN) layers with low overall defect density and
      high crystalline quality were grown on r-plane sapphire substrates using etched a
      GaN. The a-GaN layer was etched by pulse NH3 interrupted etching. Subsequently, a
      2-um-thick Si-doped a-GaN layer was regrown on the etched a-GaN layer. A fully
      coalescent n-type a-GaN layer with a low threading dislocation density (~7.5 *
      10(8) cm(-2)) and a low basal stacking fault density (~1.8 * 10(5) cm(-1)) was
      obtained. Compared with a planar sample, the full width at half maximum of the
      (11-20) X-ray rocking curve was significantly decreased to 518 arcsec along the c
      axis direction and 562 arcsec along the m-axis direction.

PMID- 24663650
TI  - Thermodielectric generation of defect modes in a photonic liquid crystal.
AB  - Photonic defect modes induced by in situ formation of an ill-defined defect layer
      is demonstrated in a cholesteric liquid crystal (CLC). The local deformation of
      the one-dimensionally periodic helical structure is achieved by means of the
      thermodielectric effect, which alters the pitch in the middle of the cholesteric
      structure. The defect-mode peak in the photonic band gap appears in the
      transmission spectrum only when the incident circularly polarized light has the
      same handedness as that of the CLC structure. The wavelength of the deformation
      induced defect mode can be tuned upon varying the dielectric heating power by
      simply applying a frequency-modulated voltage. 

PMID- 24663651
TI  - Self-mixing dual-frequency laser Doppler velocimeter.
AB  - A self-mixing (SM) dual-frequency (DF) laser Doppler velocimeter (LDV) (SM DF
      LDV) is proposed and studied, which integrates the advantages of both the SM-LDV
      and the DF-LDV. An optically injected semiconductor laser operated in a dual
      frequency period-one (P1) dynamical state is used as the light source. By probing
      the target with the light-carried microwave generated from the beat of the two
      optical frequency components, the spectral broadening in the Doppler signal due
      to the speckle noise can be significantly reduced. Together with an SM
      configuration, the SM DF-LDV has the advantages of direction discriminability,
      self-alignment, high sensitivity, and compact setup. In this study, speckle noise
      reduction and direction discriminability with an SM DF-LDV are demonstrated. The
      signal-to-noise ratios (SNRs) at different feedback powers are investigated.
      Benefiting from the high sensitivity of the SM configuration, an SNR of 23 dB is
      achieved without employing an avalanched photodetector or photomultiplier tube.
      The velocity resolution and the SNR under different speckle noise conditions are
      studied. Average velocity resolution of 0.42 mm/s and SNR of 22.1 dB are achieved
      when a piece of paper is rotating at a transverse velocity of 5 m/s. Compared
      with a conventional single-frequency LDV (SF-LDV), the SM DF-LDV shows
      improvements of 20-fold in the velocity resolution and 8 dB in the SNR. 

PMID- 24663652
TI  - Two-photon interference with continuous-wave multi-mode coherent light.
AB  - We report two-photon interference with continuous-wave multi-mode coherent light.
      We show that the two-photon interference, in terms of the detection time
      difference, reveals two-photon beating fringes with the visibility V = 0.5. While
      scanning the optical delay of the interferometer, Hong-Ou-Mandel dips or peaks
      are measured depending on the chosen detection time difference. The HOM
      dips/peaks are repeated when the optical delay and the first-order coherence
      revival period of the multi-mode coherent light are the same. These results help
      to understand the nature of two-photon interference and also can be useful for
      quantum information science. 

PMID- 24663653
TI  - Microwave field controlled slow and fast light with a coupled system consisting
      of a nanomechanical resonator and a Cooper-pair box.
AB  - We theoretically demonstrate an efficient method to control slow and fast light
      in microwave regime with a coupled system consisting of a nanomechanical
      resonator (NR) and a superconducting Cooper-pair box (CPB). Using the pump-probe
      technique, we find that both slow and fast light effects of the probe field can
      appear in this coupled system. Furthermore, we show that a tunable switch from
      slow light to fast light can be achieved by only adjusting the pump-CPB detuning
      from the NR frequency to zero. Our coupled system may have potential
      applications, for example, in optical communication, microwave photonics, and
      nonlinear optics. 

PMID- 24663654
TI  - Silicon-organic hybrid (SOH) frequency comb sources for terabit/s data
      transmission.
AB  - We demonstrate frequency comb sources based on silicon-organic hybrid (SOH)
      electro-optic modulators. Frequency combs with line spacings of 25 GHz and 40 GHz
      are generated, featuring flat-top spectra with less than 2 dB power variations
      over up to 7 lines. The combs are used for WDM data transmission at terabit/s
      data rates and distances of up to 300 km. 

PMID- 24663655
TI  - Software defined networking (SDN) over space division multiplexing (SDM) optical
      networks: features, benefits and experimental demonstration.
AB  - We present results from the first demonstration of a fully integrated SDN
      controlled bandwidth-flexible and programmable SDM optical network utilizing
      sliceable self-homodyne spatial superchannels to support dynamic bandwidth and
      QoT provisioning, infrastructure slicing and isolation. Results show that SDN is
      a suitable control plane solution for the high-capacity flexible SDM network. It
      is able to provision end-to-end bandwidth and QoT requests according to user
      requirements, considering the unique characteristics of the underlying SDM
      infrastructure. 

PMID- 24663656
TI  - Polarization converters in highly birefringent microfibers.
AB  - A novel type of polarization converters (PCs) based on highly birefringent (Hi
      Bi) microfibers is presented. Analytical formulation based on the Jones Matrix
      method and a numerical code based on the Full Vectorial Finite Difference Beam
      Propagation Method are developed to analyze the polarization evolutions in such
      PCs. Two different design configurations, namely the "one-side" and "two-side"
      perturbation configurations, are studied by use of the two methods, and the
      results obtained agree well with each others. The PCs can be flexibly designed to
      have different operating wavelengths, spectral bandwidths, and devices lengths. A
      particular PC based on an elliptical microfiber demonstrates a bandwidth of ~ 600
      nm around 1550 nm with a device length of ~ 150 MUm. 

PMID- 24663657
TI  - Strain-enhanced cable-type 3D UV photodetecting of ZnO nanowires on a Ni wire by
      coupling of piezotronics effect and pn junction.
AB  - A 3D-sensitified and strain-enhanced UV wire-photodetector has been fabricated
      with ZnO NWs grown on an oxidized Ni wire by chemical vapor deposition method.
      The photoluminescence (PL) spectra of the device shows a sharp UV peak at around
      380 nm and a negligible peak at around 520 nm, which proves that the as-prepared
      ZnO nanowires were well-crystallized. The current-voltage (I-V) and current-time
      (I-T) characteristics under different rotation angles of the heterojunctions show
      good rectifying diode behaviors and stability under different angles which make
      3D detection possible. The sensitivity of the device is enhanced by strains due
      to piezotronic effect of ZnO nanowires. These performances of the device
      demonstrates a promising approach to 3D photodetecting and strain sensing and
      also provide a prospective application to the development of weaving single wire
      into fabrics technology. 

PMID- 24663658
TI  - Initial ranging scheme based on interpolated Zadoff-Chu sequences for OFDMA-PON.
AB  - Initial access to passive optical networks (PONs) requires upstream (US)
      synchronization of multiple optical network units (ONUs). We propose a low
      complexity scheme for orthogonal frequency division multiple access (OFDMA) based
      PONs and demonstrate it experimentally. The scheme is based on interpolated
      Zadoff-Chu sequences, to synchronize the signal of each ONU arriving at the
      optical line terminal (OLT). Our experimental test bed consists of 4 colorless
      ONUs seeded by a single laser located at the OLT. Thermal expansion of a fiber is
      utilized to emulate a dynamic time drift in the demodulation-window positioning
      of OLT. The detected individual offsets at the OLT are fed back to the ONUs and
      are compensated at every data frame transmission. In this way, both inter carrier
      interference (ICI) and inter symbol interference (ISI) remain below acceptable
      levels. 

PMID- 24663659
TI  - Influence of Raman scattering on the light field in natural waters: a simple
      assessment.
AB  - A simple, surprisingly accurate, method for estimating the influence of Raman
      scattering on the upwelling light field in natural waters is developed. The
      method is based on the single (or quasi-single) scattering solution of the
      radiative transfer equation with the Raman source function. Given the light field
      at the excitation wavelength, accurate estimates (~1-10%) of the contribution of
      Raman scattering to the light field at the emission wavelength are obtained. The
      accuracy is only slightly degraded when typically measured aspects of the light
      field at the excitation are available. 

PMID- 24663660
TI  - Carrier-envelope-phase-dependent above-threshold ionization of xenon observed
      with multi-cycle laser pulses.
AB  - Carrier-envelope-phase (CEP)-dependent modulation was measured in above-threshold
      ionization of xenon driven with 30-fs laser pulses. We showed the dependence from
      the asymmetry map obtained using a velocity map imaging spectrometer, up to 17 eV
      in photoelectron energy. The dependence appeared to be linear with a slope of one
      photon energy increase per CEP change of 2pi and did not rely on the sign or the
      amount of laser chirp. Our results indicated the existence of the quantum
      interference between different multiphoton ionization paths. 

PMID- 24663661
TI  - Enhancement of color saturation and color gamut enabled by a dual-band color
      filter exhibiting an adjustable spectral response.
AB  - The enhancement of color saturation and color gamut has been demonstrated, by
      taking advantage of a dual-band color filter based on a subwavelength rectangular
      metal-dielectric resonant grating, which exhibits an adjustable spectral response
      with respect to its relative transmittances at the two bands of green and red,
      thereby producing any color in between green and red, through the adjustment of
      incoming light polarization. Also, the prominent features of the spectral
      response of the filter, namely the bandwidth and resonant wavelength, can be
      readily adjusted by varying the dielectric layer thickness and the grating pitch,
      respectively. The dependence of chromaticity coordinates of the filter in the CIE
      (International Commission on Illumination) 1931 chromaticity diagram upon the
      parameters of the spectral response, including the center wavelength, spectral
      bandwidth and sideband level, has been rigorously examined, and their influence
      on the color gamut and the excitation purity, which is a colorimetric measure of
      saturation, has been analytically explored at the same time, in order to optimize
      the color performance of the filters. In particular, a device with wider spectral
      bandwidth was observed to efficiently extend the color gamut and enhance the
      color saturation, i.e. the excitation purity for a given sideband level. Two dual
      band green-red filters, exhibiting different bandwidths of about 17 and 36 nm,
      were specifically designed and fabricated. As compared with the case with
      narrower bandwidth, the device with wider bandwidth was observed to provide both
      higher excitation purity leading to better color saturation and greater
      separation of the chromaticity coordinates for the filter output for different
      incident polarizations, which provides extended color gamut. The proposed device
      structure may permit the color tuning span to encompass all primary color bands,
      by adjusting the grating pitch. 

PMID- 24663662
TI  - Reflection and transmission of Gaussian beam by a uniaxial anisotropic slab.
AB  - The reflection and transmission of an incident Gaussian beam by a uniaxial
      anisotropic slab are investigated, by expanding the incident Gaussian beam,
      reflected beam, internal beam as well as transmitted beam in terms of cylindrical
      vector wave functions. The unknown expansion coefficients are determined by
      virtue of the boundary conditions. For a localized beam model, numerical results
      are provided for the normalized field intensity distributions, and the
      propagation characteristics are discussed concisely. 

PMID- 24663663
TI  - Optical performance test and validation of microcameras in multiscale, gigapixel
      imagers.
AB  - Wide field-of-view gigapixel imaging systems capable of diffraction-limited
      resolution and video-rate acquisition have a broad range of applications,
      including sports event broadcasting, security surveillance, astronomical
      observation, and bioimaging. The complexity of the system integration of such
      devices demands precision optical components that are fully characterized and
      qualified before being integrated into the final system. In this work, we present
      component and assembly level characterizations of microcameras in our first
      gigapixel camera, the AWARE-2. Based on the results of these measurements, we
      revised the optical design and assembly procedures to construct the second
      generation system, the AWARE-2 Retrofit, which shows significant improvement in
      image quality. 

PMID- 24663664
TI  - Fabricating centimeter-scale high quality factor two-dimensional periodic
      photonic crystal slabs.
AB  - We present a fabrication route for centimeter-scale two-dimensional defect-free
      photonic crystal slabs with quality factors bigger than 10,000 in the visible,
      together with a unique way to quantify their quality factors. We fabricate
      Si(3)N(4) photonic crystal slabs, and perform an angle-resolved reflection
      measurement. This measurement data is used to retrieve the quality factors of the
      slabs by fitting it to a model based on temporal coupled-mode theory. The
      macroscopic nature of the structure and the high quality factors of their
      resonances could open up new opportunities for realizing efficient macroscale
      optoelectronic devices such as sensors, lasers, and energy harvesting systems.

PMID- 24663665
TI  - Soliton families and resonant radiation in a micro-ring resonator near zero group
      velocity dispersion.
AB  - We report theoretical and numerical study of the dynamical and spectral
      properties of the conservative and dissipative solitons in micro-ring resonators
      pumped in a proximity of the zero of the group velocity dispersion. We discuss
      frequency and velocity locking of the conservative solitons, when dissipation is
      accounted for. We present theory of the dispersive radiation emitted by such
      solitons, report their Hopf instability and radiation enhancement by multiple
      solitons. 

PMID- 24663666
TI  - Evidence of trem2 variant associated with triple risk of Alzheimer's disease.
AB  - Alzheimer's disease is one of the main causes of dementia among elderly
      individuals and leads to the neurodegeneration of different areas of the brain,
      resulting in memory impairments and loss of cognitive functions. Recently, a rare
      variant that is associated with 3-fold higher risk of Alzheimer's disease onset
      has been found. The rare variant discovered is a missense mutation in the loop
      region of exon 2 of Trem2 (rs75932628-T, Arg47His). The aim of this study was to
      investigate the evidence for potential structural and functional significance of
      Trem2 gene variant (Arg47His) through molecular dynamics simulations. Our results
      showed the alteration caused due to the variant in TREM2 protein has significant
      effect on the ligand binding affinity as well as structural configuration. Based
      on molecular dynamics (MD) simulation under salvation, the results confirmed that
      native form of the variant (Arg47His) might be responsible for improved
      compactness, hence thereby improved protein folding. Protein simulation was
      carried out at different temperatures. At 300K, the deviation of the theoretical
      model of TREM2 protein increased from 2.0 A at 10 ns. In contrast, the deviation
      of the Arg47His mutation was maintained at 1.2 A until the end of the simulation
      (t = 10 ns), which indicated that Arg47His had reached its folded state. The
      mutant residue was a highly conserved region and was similar to "immunoglobulin V
      set" and "immunoglobulin-like folds". Taken together, the result from this study
      provides a biophysical insight on how the studied variant could contribute to the
      genetic susceptibility to Alzheimer's disease. 

PMID- 24663667
TI  - Repeated evolution of tricellular (and bicellular) pollen.
AB  - PREMISE OF STUDY: Male gametophytes of seed plants are sexually immature at the
      time they are dispersed as pollen, but approximately 30% of flowering plants have
      tricellular pollen containing fully formed sperm at anthesis. The classic study
      of Brewbaker (1967: American Journal of Botany 54: 1069-1083) provided a powerful
      confirmation of the long-standing hypothesis that tricellular pollen had many
      parallel and irreversible origins within angiosperms. We readdressed the main
      questions of that study with modern comparative phylogenetic methods. METHODS: We
      used our own and more recent reports to greatly expand the Brewbaker data set. We
      modeled trait evolution for 2511 species on a time-calibrated angiosperm
      phylogeny using (1) Binary State Speciation and Extinction (BiSSE), which
      accounts for the effect of species diversification rates on character transition
      rates and, (2) the hidden rates model (HRM), which incorporates variation in
      transition rates across a phylogeny. KEY RESULTS: Seventy percent of species had
      bicellular pollen. BiSSE found a 1.9-fold higher bicellular to tricellular
      transition rate than in the reverse direction, and bicellular lineages had a 1.8
      fold higher diversification rate than tricellular lineages. HRM found
      heterogeneity in evolutionary rates, with bidirectional transition rates in three
      of four rate classes. CONCLUSIONS: The tricellular condition is not irreversible.
      Pollen cell numbers are maintained at intermediate frequencies because lower net
      diversification rates of tricellular lineages are counterbalanced by slower state
      shifts to the bicellular condition. That tricellular lineages diversify slowly
      and give rise to bicellular lineages slowly reflects a linkage between the
      evolution of sporophyte lifestyles and the developmental lability of male
      gametophytes.

PMID- 24663669
TI  - Amphiphilic siderophore production by oil-associating microbes.
AB  - The Deepwater Horizon oil spill in 2010 released an unprecedented amount of oil
      into the ocean waters of the Gulf of Mexico. As a consequence, bioremediation by
      oil-degrading microbes has been a topic of increased focus. One factor limiting
      the rate of hydrocarbon degradation by microbial communities is the availability
      of necessary nutrients, including iron. The siderophores produced from two Vibrio
      spp. isolated from the Gulf of Mexico following the Deepwater Horizon oil spill,
      along with the well-studied oil-degrading microbe, Alcanivorax borkumensis SK2,
      are studied under iron-limiting conditions. Here we report the amphiphilic
      amphibactin siderophores produced by the oil-associated bacteria, Vibrio sp. S1B,
      Vibrio sp. S2A and Alcanivorax borkumensis SK2. These findings provide insight
      into oil-associating microbial iron acquisition.

PMID- 24663670
TI  - Chronic intestinal pseudo-obstruction: systematic histopathological approach can
      clinch vital clues.
AB  - The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is
      critical, and the findings are often missed by the histopathologists for lack of
      awareness and nonavailability of standard criteria. We aimed to describe a
      detailed histopathological approach for working-up cases of CIP by citing our
      experience. Eight suspected cases of CIP were included in the study to determine
      and describe an approach for reaching the histopathological diagnosis collected
      over a period of the last 1.5 years. The Hirschsprung's disease was put apart
      from the scope of this study. A detailed light microscopic analysis was performed
      along with special and immunohistochemical stains. Transmission electron
      microscopy was carried out on tissue retrieved from paraffin embedded tissue
      blocks. Among the eight cases, three were neonates, one in the pediatric age
      group, two adolescent, and two adults. After following the described critical
      approach, we achieved the histological diagnoses in all the cases. The causes of
      CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4),
      mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and
      duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in
      all of them along with other primary pathologies. One of the IND patients also
      had visceral myopathy, type IV. Histopathologists need to follow a systematic
      approach comprising of diligent histological examination and use of
      immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup.
      Therapy and prognosis vary depending on lesions identified by pathologists. These
      lesions can be seen in isolation or in combinations.

PMID- 24663672
TI  - Gestational chronodisruption impairs hippocampal expression of NMDA receptor
      subunits Grin1b/Grin3a and spatial memory in the adult offspring.
AB  - Epidemiological and experimental evidence correlates adverse intrauterine
      conditions with the onset of disease later in life. For a fetus to achieve a
      successful transition to extrauterine life, a myriad of temporally integrated
      humoral/biophysical signals must be accurately provided by the mother. We and
      others have shown the existence of daily rhythms in the fetus, with peripheral
      clocks being entrained by maternal cues, such as transplacental melatonin
      signaling. Among developing tissues, the fetal hippocampus is a key structure for
      learning and memory processing that may be anticipated as a sensitive target of
      gestational chronodisruption. Here, we used pregnant rats exposed to constant
      light treated with or without melatonin as a model of gestational
      chronodisruption, to investigate effects on the putative fetal hippocampus clock,
      as well as on adult offspring's rhythms, endocrine and spatial memory outcomes.
      The hippocampus of fetuses gestated under light:dark photoperiod (12:12 LD)
      displayed daily oscillatory expression of the clock genes Bmal1 and Per2, clock
      controlled genes Mtnr1b, Slc2a4, Nr3c1 and NMDA receptor subunits 1B-3A-3B. In
      contrast, in the hippocampus of fetuses gestated under constant light (LL), these
      oscillations were suppressed. In the adult LL offspring (reared in LD during
      postpartum), we observed complete lack of day/night differences in plasma
      melatonin and decreased day/night differences in plasma corticosterone. In the
      adult LL offspring, overall hippocampal day/night difference of gene expression
      was decreased, which was accompanied by a significant deficit of spatial memory.
      Notably, maternal melatonin replacement to dams subjected to gestational
      chronodisruption prevented the effects observed in both, LL fetuses and adult LL
      offspring. Collectively, the present data point to adverse effects of gestational
      chronodisruption on long-term cognitive function; raising challenging questions
      about the consequences of shift work during pregnancy. The present study also
      supports that developmental plasticity in response to photoperiodic cues may be
      modulated by maternal melatonin. 

PMID- 24663674
TI  - Insights into the origin of nematode chemosensory GPCRs: putative orthologs of
      the Srw family are found across several phyla of protostomes.
AB  - Nematode chemosensory GPCRs in Caenorhabditis elegans (NemChRs) are classified
      into 19 gene families, and are initially thought to have split from the ancestral
      Rhodopsin family of GPCRs. However, earlier studies have shown that among all 19
      NemChR gene families, only the srw family has a clear sequence relationship to
      the ancestral Rhodopsin GPCR family. Yet, the phylogenetic relationships between
      the srw family of NemChRs and the Rhodopsin subfamilies are not fully understood.
      Also, a widespread search was not previously performed to check for the presence
      of putative srw family-like sequences or the other 18 NemChR families in several
      new protostome species outside the nematode lineage. In this study, we have
      investigated for the presence of 19 NemChR families across 26 eukaryotic species,
      covering basal eukaryotic branches and provide the first evidence that the srw
      family of NemChRs is indeed present across several phyla of protostomes. We could
      identify 29 putative orthologs of the srw family in insects (15 genes), molluscs
      (11 genes) and Schistosoma mansoni (3 genes). Furthermore, using HMM-HMM profile
      based comparisons and phylogenetic analysis we show that among all Rhodopsin
      subfamilies, the peptide and SOG (somatostatin/opioid/galanin) subfamilies are
      phylogenetically the closest relatives to the srw family of NemChRs. Taken
      together, we demonstrate that the srw family split from the large Rhodopsin
      family, possibly from the peptide and/or SOG subfamilies, well before the split
      of the nematode lineage, somewhere close to the divergence of the common ancestor
      of protostomes. Our analysis also suggests that the srsx family of NemChRs shares
      a clear sequence homology with the Rhodopsin subfamilies, as well as with few of
      the vertebrate olfactory receptors. Overall, this study provides further insights
      into the evolutionary events that shaped the GPCR chemosensory system in
      protostome species. 

PMID- 24663673
TI  - Preserved coupling between the reader's voice and the listener's cortical
      activity in autism spectrum disorders.
AB  - PURPOSE: Investigating the steadiness of the phase-coupling between the time
      course of the reader's voice and brain signals of subjects with autism spectrum
      disorder (ASD) passively listening to connected speech using
      magnetoencephalography (MEG). In typically developed subjects, such coupling
      occurs at the right posterior temporal sulcus (pSTS) for frequencies below 1 Hz,
      and reflects the neural processing of sentence-level rhythmic prosody at the
      prelexical level. METHODS: Cortical neuromagnetic signals were recorded with MEG
      (Elekta Oy, Finland) while seven right-handed and native French-speaking ASD
      subjects (six males, one female, range: 13-20 years) listened to live (Live) or
      recorded (Recorded) voices continuously reading a text in French for five
      minutes. Coherence was computed between the reader's voice time-course and ASD
      subjects' MEG signals. Coherent neural sources were subsequently reconstructed
      using a beamformer. KEY FINDINGS: Significant coupling was found at 0.5 Hz in all
      ASD subjects in Live and in six subjects in Recorded. Coherent sources were
      located close to the right pSTS in both conditions. No significant difference was
      found in coherence levels between Live and Recorded, and between ASD subjects and
      ten typically developed subjects (right-handed, native French-speaking adults, 5
      males, 5 females, age range: 21-38 years) included in a previous study.
      SIGNIFICANCE: This study discloses a preserved coupling between the reader's
      voice and ASD subjects' cortical activity at the right pSTS. These findings
      support the existence of preserved neural processing of sentence-level rhythmic
      prosody in ASD. The preservation of early cortical processing of prosodic
      elements in verbal language might be exploited in therapeutic interventions in
      ASD.

PMID- 24663675
TI  - Reduced regulatory T cell diversity in NOD mice is linked to early events in the
      thymus.
AB  - The thymic natural regulatory T cell (Treg) compartment of NOD mice is unusual in
      having reduced TCR diversity despite normal cellularity. In this study, we show
      that this phenotype is attributable to perturbations in early and late stages of
      thymocyte development and is controlled, at least in part, by the NOD Idd9 region
      on chromosome 4. Progression from double negative 1 to double negative 2 stage
      thymocytes in NOD mice is inefficient; however, this defect is compensated by
      increased proliferation of natural Tregs (nTregs) within the single positive CD4
      thymocyte compartment, accounting for recovery of cellularity accompanied by loss
      of TCR diversity. This region also underlies the known attenuation of ERK-MAPK
      signaling, which may preferentially disadvantage nTreg selection. Interestingly,
      the same genetic region also regulates the rate of thymic involution that is
      accelerated in NOD mice. These findings highlight further complexity in the
      control of nTreg repertoire diversity. 

PMID- 24663676
TI  - A novel mechanism underlying the basic defensive response of macrophages against
      Mycobacterium infection.
AB  - Following inhalation of Mycobacterium tuberculosis, including bacillus Calmette
      Guerin (BCG), pathogens enter and grow inside macrophages by taking advantage of
      their phagocytic mechanisms. Macrophages often fail to eliminate intracellular M.
      tuberculosis, leading to the induction of host macrophage death. Despite
      accumulating evidence, the molecular mechanisms underlying M. tuberculosis
      infection-induced cell death remain controversial. In this study, we show the
      involvement of two distinct pathways triggered by TLR2 and beta2 integrin in BCG
      infection-induced macrophage apoptosis. First, BCG infection induced activation
      of ERK1/2, which in turn caused phosphorylation/activation of the proapoptotic
      protein Bim in mouse macrophage-like Raw 264.7 cells. BCG-infected Raw cells
      treated with U0126, an MEK/ERK inhibitor, led to the suppression of Bim
      phosphorylation alongside a remarkable increase in the number of viable
      macrophages. Small interfering RNA-mediated knockdown of Bim rescued the
      macrophages from the apoptotic cell death induced by BCG infection. Stimulation
      with Pam3CSK, a TLR2 agonist, induced macrophage apoptosis with a concomitant
      increase in the phosphorylation/activation of MEK/ERK and Bim. These observations
      indicate the important role of the TLR2/MEK/ERK/Bim pathway in BCG infection
      induced macrophage apoptosis. Second, we used the beta2 integrin agonists C3bi
      and fibronectin to show that the beta2 integrin-derived signal was involved in
      BCG infection-induced apoptosis, independent of MEK/ERK activation.
      Interestingly, latex beads coated with Pam3CSK and C3bi were able to induce
      apoptosis in macrophages to the same extent and specificity as that induced by
      BCG. Taken together, two distinct pattern-recognition membrane receptors, TLR2
      and beta2 integrin, acted as triggers in BCG infection-induced macrophage
      apoptosis, in which MEK/ERK activation played a crucial role following the
      engagement of TLR2. 

PMID- 24663678
TI  - Interplay between CXCR2 and BLT1 facilitates neutrophil infiltration and
      resultant keratinocyte activation in a murine model of imiquimod-induced
      psoriasis.
AB  - Psoriasis is an inflammatory skin disease with accelerated epidermal cell
      turnover. Neutrophil accumulation in the skin is one of the histological
      characteristics of psoriasis. However, the precise mechanism and role of
      neutrophil infiltration remain largely unknown. In this article, we show that
      orchestrated action of CXCR2 and leukotriene B4 receptor BLT1 plays a key role in
      neutrophil recruitment during the development of imiquimod (IMQ)-induced
      psoriatic skin lesions in mice. Depletion of neutrophils with anti-Ly-6G Ab
      ameliorated the disease severity, along with reduced expression of
      proinflammatory cytokine IL-1beta in the skin. Furthermore, CXCR2 and BLT1
      coordinately promote neutrophil infiltration into the skin during the early phase
      of IMQ-induced inflammation. In vitro, CXCR2 ligands augment leukotriene B4
      production by murine neutrophils, which, in turn, amplifies chemokine-mediated
      neutrophil chemotaxis via BLT1 in autocrine and/or paracrine manners. In
      agreement with the increased IL-19 expression in IMQ-treated mouse skin, IL-1beta
      markedly upregulated expression of acanthosis-inducing cytokine IL-19 in human
      keratinocytes. We propose that coordination of chemokines, lipids, and cytokines
      with multiple positive feedback loops might drive the pathogenesis of psoriasis
      and, possibly, other inflammatory diseases as well. Interference to this positive
      feedback or its downstream effectors could be targets of novel anti-inflammatory
      treatment. 

PMID- 24663679
TI  - 1,25-Dihydroxyvitamin D3 promotes tolerogenic dendritic cells with functional
      migratory properties in NOD mice.
AB  - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3], is able to promote the generation of tolerogenic mature dendritic
      cells (mDCs) with an impaired ability to activate autoreactive T cells. These
      cells could represent a reliable tool for the promotion or restoration of Ag
      specific tolerance through vaccination strategies, for example in type 1 diabetes
      patients. However, successful transfer of 1,25(OH)2D3-treated mDCs (1,25D3-mDCs)
      depends on the capacity of 1,25(OH)2D3 to imprint a similar tolerogenic profile
      in cells derived from diabetes-prone donors as from diabetes-resistant donors. In
      this study, we examined the impact of 1,25(OH)2D3 on the function and phenotype
      of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show
      that 1,25(OH)2D3 is able to imprint a phenotypic tolerogenic profile on DCs
      derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D3-mDCs
      decreased the proliferation and activation of autoreactive T cells in vitro,
      despite strain differences in the regulation of cytokine/chemokine expression. In
      addition, 1,25D3-mDCs from diabetes-prone mice expanded CD25(+)Foxp3(+)
      regulatory T cells and induced intracellular IL-10 production by T cells in
      vitro. Furthermore, 1,25D3-mDCs exhibited an intact functional migratory capacity
      in vivo that favors homing to the liver and pancreas of adult NOD mice. More
      importantly, when cotransferred with activated CD4(+) T cells into NOD.SCID
      recipients, 1,25D3-mDCs potently dampened the proliferation of autoreactive donor
      T cells in the pancreatic draining lymph nodes. Altogether, these results argue
      for the potential of 1,25D3-mDCs to restore Ag-specific immune tolerance and
      arrest autoimmune disease progression in vivo. 

PMID- 24663681
TI  - Families, pediatricians, and the challenges of digital kids: the best of times?

PMID- 24663677
TI  - Airway uric acid is a sensor of inhaled protease allergens and initiates type 2
      immune responses in respiratory mucosa.
AB  - Although type 2 immune responses to environmental Ags are thought to play pivotal
      roles in asthma and allergic airway diseases, the immunological mechanisms that
      initiate the responses are largely unknown. Many allergens have biologic
      activities, including enzymatic activities and abilities to engage innate pattern
      recognition receptors such as TLR4. In this article, we report that IL-33 and
      thymic stromal lymphopoietin were produced quickly in the lungs of naive mice
      exposed to cysteine proteases, such as bromelain and papain, as a model for
      allergens. IL-33 and thymic stromal lymphopoietin sensitized naive animals to an
      innocuous airway Ag OVA, which resulted in production of type 2 cytokines and IgE
      Ab, and eosinophilic airway inflammation when mice were challenged with the same
      Ag. Importantly, upon exposure to proteases, uric acid (UA) was rapidly released
      into the airway lumen, and removal of this endogenous UA by uricase prevented
      type 2 immune responses. UA promoted secretion of IL-33 by airway epithelial
      cells in vitro, and administration of UA into the airways of naive animals
      induced extracellular release of IL-33, followed by both innate and adaptive type
      2 immune responses in vivo. Finally, a potent UA synthesis inhibitor, febuxostat,
      mitigated asthma phenotypes that were caused by repeated exposure to natural
      airborne allergens. These findings provide mechanistic insights into the
      development of type 2 immunity to airborne allergens and recognize airway UA as a
      key player that regulates the process in respiratory mucosa. 

PMID- 24663680
TI  - Improved functional expression of human cardiac kv1.5 channels and trafficking
      defective mutants by low temperature treatment.
AB  - We herein investigated the effect of low temperature exposure on the expression,
      degradation, localization and activity of human Kv1.5 (hKv1.5). In hKv1.5
      expressing CHO cells, the currents were significantly increased when cultured at
      a reduced temperature (28 degrees C) compared to those observed at 37 degrees C.
      Western blot analysis indicated that the protein levels (both immature and mature
      proteins) of hKv1.5 were significantly elevated under the hypothermic condition.
      Treatment with a proteasome inhibitor, MG132, significantly increased the
      immature, but not the mature, hKv1.5 protein at 37 degrees C, however, there were
      no changes in either the immature or mature hKv1.5 proteins at low temperature
      following MG132 exposure. These observations suggest that the enhancement of the
      mature hKv1.5 protein at reduced temperature may not result from the inhibition
      of proteolysis. Moreover, the hKv1.5 fluorescence signal in the cells increased
      significantly on the cell surface at 28 degrees C versus those cultured at 37
      degrees C. Importantly, the low temperature treatment markedly shifted the
      subcellular distribution of the mature hKv1.5, which showed considerable overlap
      with the trans-Golgi component. Experiments using tunicamycin, an inhibitor of N
      glycosylation, indicated that the N-glycosylation of hKv1.5 is more effective at
      28 degrees C than at 37 degrees C. Finally, the hypothermic treatment also
      rescued the protein expression and currents of trafficking-defective hKv1.5
      mutants. These results indicate that low temperature exposure stabilizes the
      protein in the cellular organelles or on the plasma membrane, and modulates its
      maturation and trafficking, thus enhancing the currents of hKv1.5 and its
      trafficking defect mutants. 

PMID- 24663682
TI  - Dental Anomalies Associated with Craniometaphyseal Dysplasia.
AB  - Craniometaphyseal dysplasia (CMD) is a rare genetic disorder encompassing
      hyperostosis of craniofacial bones and metaphyseal widening of tubular bones.
      Dental abnormalities are features of CMD that have been little discussed in the
      literature. We performed dentofacial examination of patients with CMD and
      evaluated consequences of orthodontic movement in a mouse model carrying a CMD
      knock-in (KI) mutation (Phe377del) in the Ank gene. All patients have a history
      of delayed eruption of permanent teeth. Analysis of data obtained by cone-beam
      computed tomography showed significant bucco-lingual expansion of jawbones, more
      pronounced in mandibles than in maxillae. There was no measurable increase in
      bone density compared with that in unaffected individuals. Orthodontic
      cephalometric analysis showed that patients with CMD tend to have a short
      anterior cranial base, short upper facial height, and short maxillary length.
      Microcomputed tomography (micro-CT) analysis in homozygous Ank (KI/KI) mice, a
      model for CMD, showed that molars can be moved by orthodontic force without
      ankylosis, however, at a slower rate compared with those in wild-type Ank (+/+)
      mice (p < .05). Histological analysis of molars in Ank (KI/KI) mice revealed
      decreased numbers of TRAP(+) osteoclasts on the bone surface of pressure sides.
      Based on these findings, recommendations for the dental treatment of patients
      with CMD are provided. 

PMID- 24663684
TI  - Development of the Childbirth Perception Scale (CPS): perception of delivery and
      the first postpartum week.
AB  - Some caregivers suggest a more positive experience of childbirth when giving
      birth at home. Since properly developed instruments that assess women's
      perception of delivery and the early postpartum are missing, the aim of the
      current study is to develop a Childbirth Perception Scale (CPS). Three focus
      groups with caregivers, pregnant women, and women who recently gave birth were
      conducted. Psychometric properties of 23 candidate items derived from the
      interviews were tested with explorative factor analysis (EFA) (N = 495).
      Confirmatory factor analysis (CFA) was performed in another sample of women (N =
      483) and confirmed a 12-item CPS. The EFA in sample I suggested a two-component
      solution: a subscale 'perception of delivery' (six items) and a subscale
      'perception of the first postpartum week' (six items). The CFA in sample II
      confirmed an adequate model fit and a good internal consistency (alpha = .82).
      Multivariate linear regression showed a positive effect of home delivery on
      perception of delivery in multiparous but not in primiparous women. The 12-item
      CPS with two dimensions (perception of delivery and perception of first
      postpartum week) has adequate psychometric properties. In multiparous women, home
      delivery showed to be independently related to more positive perception of
      delivery.

PMID- 24663683
TI  - Human Papillomavirus (HPV)-associated Oral Cancers and Treatment Strategies.
AB  - Human papillomavirus (HPV) is known to be associated with several types of human
      cancer, including cervical, vulvar, vaginal, penile, anal, and head-and-neck
      cancers. Among these cancers, HPV-associated head-and-neck cancers, inclusive of
      oropharyngeal squamous cell carcinoma (OSCC) and oral cavity squamous cell
      carcinomas (OCSCC), have recently risen dramatically in men under 50 years old.
      Within 20 years, the percentage of HPV-positive OSCC in total OSCC went from less
      than 20% to more than 70% in the United States and some European countries. This
      article reviews the incidence trend and pathogenesis of HPV-associated head-and
      neck cancers as well as current treatment modalities for the disease. 

PMID- 24663685
TI  - Low maternal serum vitamin D during pregnancy and the risk for postpartum
      depression symptoms.
AB  - Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an
      emerging literature associating low levels of 25(OH)-vitamin D with depressive
      symptoms. However, the link between 25(OH)-vitamin D status in pregnancy and
      altered risk of postnatal depressive symptoms has not been examined. We
      hypothesise that low levels of 25(OH)-vitamin D in maternal serum during
      pregnancy will be associated with a higher incidence of postpartum depressive
      symptoms. We prospectively collected sera at 18 weeks gestation from 796 pregnant
      women in Perth (1989-1992) who were enrolled in the Western Australian Pregnancy
      Cohort (Raine) Study and measured levels of 25(OH)-vitamin D. Women reported
      postnatal depressive symptoms at 3 days post-delivery. Women in the lowest
      quartile for 25(OH)-vitamin D status were more likely to report a higher level of
      postnatal depression symptoms than women who were in the highest quartile for
      vitamin D, even after accounting for a range of confounding variables including
      season of birth, body mass index and sociodemographic factors. Low vitamin D
      during pregnancy is a risk factor for the development of postpartum depression
      symptoms. 

PMID- 24663686
TI  - Adaptive Parametric Spectral Estimation with Kalman Smoothing for Online Early
      Seizure Detection.
AB  - Tracking spectral changes in neural signals, such as local field potentials
      (LFPs) and scalp or intracranial electroencephalograms (EEG, iEEG), is an
      important problem in early detection and prediction of seizures. Most approaches
      have focused on either parametric or nonparametric spectral estimation methods
      based on moving time windows. Here, we explore an adaptive (time-varying)
      parametric ARMA approach for tracking spectral changes in neural signals based on
      the fixed-interval Kalman smoother. We apply the method to seizure detection
      based on spectral features of intracortical LFPs recorded from a person with
      pharmacologically intractable focal epilepsy. We also devise and test an approach
      for real-time tracking of spectra based on the adaptive parametric method with
      the fixed-interval Kalman smoother. The order of ARMA models is determined via
      the AIC computed in moving time windows. We quantitatively demonstrate the
      advantages of using the adaptive parametric estimation method in seizure
      detection over nonparametric alternatives based exclusively on moving time
      windows. Overall, the adaptive parametric approach significantly improves the
      statistical separability of interictal and ictal epochs.

PMID- 24663687
TI  - Model-assisted analysis of spatial and temporal variations in fruit temperature
      and transpiration highlighting the role of fruit development.
AB  - Fruit physiology is strongly affected by both fruit temperature and water losses
      through transpiration. Fruit temperature and its transpiration vary with
      environmental factors and fruit characteristics. In line with previous studies,
      measurements of physical and thermal fruit properties were found to significantly
      vary between fruit tissues and maturity stages. To study the impact of these
      variations on fruit temperature and transpiration, a modelling approach was used.
      A physical model was developed to predict the spatial and temporal variations of
      fruit temperature and transpiration according to the spatial and temporal
      variations of environmental factors and thermal and physical fruit properties.
      Model predictions compared well to temperature measurements on mango fruits,
      making it possible to accurately simulate the daily temperature variations of the
      sunny and shaded sides of fruits. Model simulations indicated that fruit
      development induced an increase in both the temperature gradient within the fruit
      and fruit water losses, mainly due to fruit expansion. However, the evolution of
      fruit characteristics has only a very slight impact on the average temperature
      and the transpiration per surface unit. The importance of temperature and
      transpiration gradients highlighted in this study made it necessary to take
      spatial and temporal variations of environmental factors and fruit
      characteristics into account to model fruit physiology. 

PMID- 24663688
TI  - Detection of Ralstonia solanacearum from asymptomatic tomato plants, irrigation
      water, and soil through non-selective enrichment medium with hrp gene-based bio
      PCR.
AB  - Bacterial wilt of tomato caused by Ralstonia solanacearum (Smith) Yabuuchi et al.
      (Microbiol Immunol 39:897-904, 1995) is a serious disease, which causes losses up
      to 60 % depending on environmental conditions, soil property, and cultivars. In
      present investigation, nucleotide sequences of virulence, hypersensitive response
      and pathogenicity (hrp) gene were used to design a pair of primer (Hrp_rs 2F: 5'
      AGAGGTCGACGCGATACAGT-3' and Hrp_rs 2R: 5'-CATGAGCAAGGACGAAGTCA-3') for
      amplification of bacterial genome. The genomic DNA of 27 isolates of R.
      solanacearum race 1 biovar 3 & 4 was amplified at 323 bp. The specificity of
      primer was tested on 13 strains of R. solanacearum with other group of bacteria
      such as Xanthomonas oryzae pv. oryzae, X. campestris pv. campestris, and X. citri
      subsp. citri. Primer amplified DNA fragment of R. solanacearum at 323 bp. The
      sensitivity of the primer was 200 cfu/ml and improved further detection level by
      using non-specific enrichment medium casamino acids-pepton-glucose broth followed
      by PCR (BIO-PCR). Out of 130 samples of asymptomatic tomato plants, irrigation
      water, and soil collected from bacterial wilt infested field in different agro
      climatic regions of India, R. solanacearum was detected from 86.9, 88.5, and 90.9
      per cents samples using BIO-PCR, respectively. The primer was found specific for
      detecting viable and virulent strains of R. solanacearum and useful for the
      diagnosis of R. solanacearum in tomato seedlings and monitoring of pathogen in
      irrigation water and soil.

PMID- 24663690
TI  - Germanium nanoparticles encapsulated in flexible carbon nanofibers as self
      supported electrodes for high performance lithium-ion batteries.
AB  - Germanium is a promising high-capacity anode material for lithium ion batteries,
      but still suffers from poor cyclability due to its huge volume variation during
      the Li-Ge alloy/dealloy process. Here we rationally designed a flexible and self
      supported electrode consisting of Ge nanoparticles encapsulated in carbon
      nanofibers (Ge-CNFs) by using a facile electrospinning technique as potential
      anodes for Li-ion batteries. The Ge-CNFs exhibit excellent electrochemical
      performance with a reversible specific capacity of ~1420 mA h g(-1) after 100
      cycles at 0.15 C with only 0.1% decay per cycle (the theoretical specific
      capacity of Ge is 1624 mA h g(-1)). When cycled at a high current of 1 C, they
      still deliver a reversible specific capacity of 829 mA h g(-1) after 250 cycles.
      The strategy and design are simple, effective, and versatile. This type of
      flexible electrodes is a promising solution for the development of flexible
      lithium-ion batteries with high power and energy densities. 

PMID- 24663689
TI  - Monitoring dental-unit-water-line output water by current in-office test kits.
AB  - The importance of monitoring contamination levels in the output water of dental
      unit-water-lines (DUWLs) is essential as they are prone to developing biofilms
      that may contaminate water that is used to treat patients, with opportunistic
      pathogens such as species of Legionella, Pseudomonas and others. Dentists and
      practice staff are also at risk of being infected by means of cross-infection due
      to aerosols generated from DUWL water. The unit of measurement for the microbial
      contamination of water by aerobic mesophilic heterotrophic bacteria is the colony
      forming unit per millilitre (cfu/ml) of water. The UK has its own guidelines set
      by the Department of Health for water discharged from DUWL to be between 100 and
      200 cfu/ml of water. The benchmark or accepted standard laboratory test is by
      microbiological culture on R2A agar plates. However, this is costly and not
      convenient for routine testing in dental practices. A number of commercial
      indicator tests are used in dental surgeries, but they were not developed for the
      dental market and serve only to indicate gross levels of contamination when used
      outside of the manufacturer's recommended incubation period. The aim of this
      article is to briefly review the universal problem of DUWL contamination with
      microbial biofilms and to update dental professionals on the availability of
      currently available commercial in-office monitoring systems for aerobic
      mesophilic heterotrophic bacteria and to discuss their limitations for testing
      water samples in assuring compliance with recommended guidelines.

PMID- 24663691
TI  - Soliton self-frequency shift and third-harmonic generation in a four-hole As2S5
      microstructured optical fiber.
AB  - Soliton self-frequency shift (SSFS) and third-harmonic generation (THG) are
      observed in a four-hole As2S5 chalcogenide microstructured optical fiber (MOF).
      The As2S5 MOF is tapered to offer an ideal environment for SSFS. After tapering,
      the zero-dispersion wavelength (ZDW) shifts from 2.02 to 1.61 MUm, and the rate
      of SSFS can be enhanced by increasing the energy density of the pulse. By varying
      the average input power from 220 to 340 mW, SSFS of a soliton central wavelength
      from 2.206 to 2.600 MUm in the mid-infrared is observed in the tapered segment,
      and THG at 632 nm is observed in the untapered segment.

PMID- 24663692
TI  - High-Q terahertz Fano resonance with extraordinary transmission in concentric
      ring apertures.
AB  - We experimentally demonstrate a polarization-independent terahertz Fano resonance
      with extraordinary transmission when light passes through two concentric
      subwavelength ring apertures in the metal film. The Fano resonance is enabled by
      the coupling between a high-Q dark mode and a low-Q bright mode. We find the Q
      factor of the dark mode ranges from 23 to 40, which is 3~6 times higher than Q of
      bright mode. We show the Fano resonance can be tuned by varying the geometry and
      dimension of the structures. We also demonstrate a polarization dependent Fano
      resonance in a modified structure of concentric ring apertures. 

PMID- 24663693
TI  - Accurate determination of the rotational constants of ultracold molecules using
      double photoassociation spectroscopy.
AB  - We report on an accurate determination of the rotational constants of the
      ultracold long-range Cesium molecules in near dissociation domain. The scheme
      relies on a precise reference of the frequency difference in a double
      photoassociation spectroscopy induced by two laser beams based on an acoustic
      optical modulator. The rotational constants are obtained by fitting a non-rigid
      rotor model into the frequency intervals of the neighboring rotational levels
      deduced from the reference. 

PMID- 24663694
TI  - An optically controlled phased array antenna based on single sideband
      polarization modulation.
AB  - A novel optically controlled phased array antenna consisting a simple optical
      beamforming network and an N element linear patch antenna array is proposed and
      demonstrated. The optical beamforming network is realized by N independent phase
      shifters using a shared optical single sideband (OSSB) polarization modulator
      together with N polarization controllers (PCs), N polarization beam splitters
      (PBSs) and N photodetectors (PDs). An experiment is carried out. A 4-element
      linear patch antenna array operating at 14 GHz and a 1 * 4 optical beamforming
      network (OBFN) is employed to realize the phased array antenna. The radiation
      patterns of the phased array antenna at -30 degrees , 0 degrees  and 30 degrees 
      are achieved. 

PMID- 24663695
TI  - Photonic band structure and transmission analysis of cholesteric blue phase II:
      electrostriction in the [100] direction.
AB  - The photonic band structure and transmission properties of a cholesteric blue
      phase II liquid crystal, which is elongated in the [100] direction by
      electrostriction, are analyzed by finite-difference time-domain method. The
      simple cubic lattice deforms into a tetragonal lattice under the influence of an
      electric field, resulting in a change of the photonic band structure. Moreover,
      we show that the circular polarization dependence of the transmittance spectrum
      changes in an electric field, a behavior that has yet to be observed in
      experiment. 

PMID- 24663696
TI  - Optimizing low loss negative index metamaterial for visible spectrum using
      differential evolution: comment.
AB  - In a recent paper, Zhao et al. [Opt. Express 19(12), 11605 (2011)], proposed the
      use of differential evolution technique to optimize figure of merit of a negative
      index metamaterial (NIM) for the visible spectrum. In this comment, we argue that
      certain ambiguities associated with the effective parameter retrieval should be
      also addressed in the paper for the accurate implementation of the technique for
      NIMs. Furthermore, the figure of merit reported in the paper is unrealistically
      large. 

PMID- 24663697
TI  - Optimizing low loss negative index metamaterial for visible spectrum using
      differential evolution: reply.
AB  - We reply to the comment written by Aslam and Guney on our previous paper, Zhao et
      al. [Opt. Express 19(12), 11605-11614 (2011)]. We maintain that the proposed
      implementation of the DE algorithm for NIMs optimization in our work is correct,
      and the mentioned ambiguities in the comment due to the existence of multiple
      branches for n' in the retrieval procedure have been considered and eliminated by
      using the proposed robust retrieval method. Furthermore, the FOM of 15.2 for the
      DE-designed optimal fishnet structure reported in our work is reasonable for
      ideal fabrication conditions. 

PMID- 24663698
TI  - Polarization rotator-splitters in standard active silicon photonics platforms.
AB  - We demonstrate various silicon-on-insulator polarization management structures
      based on a polarization rotator-splitter that uses a bi-level taper TM0-TE1 mode
      converter. The designs are fully compatible with standard active silicon
      photonics platforms with no new levels required and were implemented in the IME
      baseline and IME-OpSIS silicon photonics processes. We demonstrate a polarization
      rotator-splitter with polarization crosstalk < -13 dB over a bandwidth of 50 nm.
      Then, we improve the crosstalk to < -22 dB over a bandwidth of 80 nm by
      integrating the polarization rotator-splitter with directional coupler
      polarization filters. Finally, we demonstrate a polarization controller by
      integrating the polarization rotator-splitters with directional couplers, thermal
      tuners, and PIN diode phase shifters. 

PMID- 24663699
TI  - Multi-element fiber technology for space-division multiplexing applications.
AB  - A novel technological approach to space division multiplexing (SDM) based on the
      use of multiple individual fibers embedded in a common polymer coating material
      is presented, which is referred to as Multi-Element Fiber (MEF). The approach
      ensures ultralow crosstalk between spatial channels and allows for cost-effective
      ways of realizing multi-spatial channel amplification and signal
      multiplexing/demultiplexing. Both the fabrication and characterization of a
      passive 3-element MEF for data transmission, and an active 5-element
      erbium/ytterbium doped MEF for cladding-pumped optical amplification that uses
      one of the elements as an integrated pump delivery fiber is reported. Finally,
      both components were combined to emulate an optical fiber network comprising SDM
      transmission lines and amplifiers, and illustrate the compatibility of the
      approach with existing installed single-mode WDM fiber systems. 

PMID- 24663700
TI  - Picosecond all-optical switching in hydrogenated amorphous silicon microring
      resonators.
AB  - We utilize cross-phase modulation to observe all-optical switching in microring
      resonators fabricated with hydrogenated amorphous silicon (a-Si:H). Using 2.7-ps
      pulses from a mode-locked fiber laser in the telecom C-band, we observe optical
      switching of a cw telecom-band probe with full-width at half-maximum switching
      times of 14.8 ps, using approximately 720 fJ of energy deposited in the
      microring. In comparison with telecom-band optical switching in undoped
      crystalline silicon microrings, a-Si:H exhibits substantially higher switching
      speeds due to reduced impact of free-carrier processes. 

PMID- 24663701
TI  - High-quality planar light emitting diode formed by induced two-dimensional
      electron and hole gases.
AB  - A high-quality planar two-dimensional p-i-n light emitting diode in an entirely
      undoped GaAs/AlGaAs quantum well has been fabricated by using conventional
      lithography process. With twin gate design, two-dimensional electron and hold
      gases can be placed closely on demand. The electroluminescence of the device
      exhibit high stability and clear transition peaks so it is promising for
      applications on electrically-driven single photon sources. 

PMID- 24663702
TI  - Diode-pumped continuous wave and passively Q-switched Tm, Mg: LiTaO3 lasers.
AB  - We have demonstrated the continuous wave and passively Q-switched Tm, Mg: LiTaO3
      lasers for the first time. In continuous wave (CW) regime, a maximum CW output
      power of 1.03 W at 1952 nm was obtained, giving a slope efficiency of 9.5% and a
      beam quality M2 = 2.2. In passive Q-switching regime, a single walled carbon
      nanotube (SWCNT) was employed as saturable absorber (SA). The Tm,Mg:LiTaO3 laser
      has yielded a pulse of 560 ns under repetition rate of 34.2 kHz at 1926 nm,
      corresponding to a single pulse energy of 10.1 MUJ. The results indicate a
      promising potential of nonlinear crystals in the applications for laser host
      materials.

PMID- 24663703
TI  - Growth model for laser-induced damage on the exit surface of fused silica under
      UV, ns laser irradiation.
AB  - We present a comprehensive statistical model which includes both the probability
      of growth and growth rate to describe the evolution of exit surface damage sites
      on fused silica optics over multiple laser shots spanning a wide range of
      fluences. We focus primarily on the parameterization of growth rate distributions
      versus site size and laser fluence using Weibull statistics and show how this
      model is consistent with established fracture mechanics concepts describing
      brittle materials. Key growth behaviors and prediction errors associated with the
      present model are also discussed. 

PMID- 24663704
TI  - Spatially-resolved self-heterodyne spectroscopy of lateral modes of broad-area
      laser diodes.
AB  - We investigate the fine structure of the optical spectrum of a broad-area laser
      diode with approximately 30-MHz resolution using spatially-resolved self
      heterodyning technique. We show that this method is capable of measuring the
      relative powers and spacings of the individual lateral modes. 

PMID- 24663705
TI  - A L0 sparse analysis prior for blind poissonian image deconvolution.
AB  - This paper proposes a new approach for blindly deconvolving images that are
      contaminated by Poisson noise. The proposed approach incorporates a new prior,
      that is the L0 sparse analysis prior, together with the total variation
      constraint into the maximum a posteriori (MAP) framework for deconvolution. A
      greedy analysis pursuit numerical scheme is exploited to solve the L0 regularized
      MAP problem. Experimental results show that our approach not only produces smooth
      results substantially suppressing artifacts and noise, but also preserves
      intensity changes sharply. Both quantitative and qualitative comparisons to the
      specialized state-of-the-art algorithms demonstrate its superiority.

PMID- 24663706
TI  - Supercontinuum generation by multiple scatterings at a group velocity horizon.
AB  - A new scheme for supercontinuum generation covering more than one octave and
      exhibiting extraordinary high coherence properties has recently been proposed
      [Phys. Rev. Lett. 110, 233901 (2013)]. The scheme is based on two-pulse collision
      at a group velocity horizon between a dispersive wave and a soliton. Here we
      demonstrate that the same scheme can be exploited for the generation of
      supercontinua encompassing the entire transparency region of fused silica,
      ranging from 300 to 2300nm. At this bandwidth extension, the Raman effect becomes
      detrimental, yet may be compensated by using a cascaded collision process.
      Consequently, the high degree of coherence does not degrade even in this extreme
      scenario. 

PMID- 24663707
TI  - Evolution of conically diffracted Gaussian beams in free space.
AB  - We present results of our observations on the free space evolution of conically
      diffracted beams from both single and cascade systems using various combinations
      of four biaxial crystals of the monoclinic double tungstate family [KGd(WO4)2].
      Longitudinal shifts and radii of the Hamilton-Lloyd pair of rings were measured.
      In each case, the symmetric - forward and backward - evolution of the beam in
      free space from its focal image plane was monitored and quantified. Theoretical
      ring plane patterns based on a recently presented theoretical model are also
      compared to experimental patterns and found to be in good agreement.

PMID- 24663708
TI  - Ultra-compact 8 * 8 strictly-non-blocking Si-wire PILOSS switch.
AB  - We report on a path-independent insertion-loss (PILOSS) 8 * 8 matrix switch based
      on Si-wire waveguides, which has a record-small footprint of 3.5 * 2.4 mm2. The
      PILOSS switch consists of 64 thermooptic Mach-Zehnder (MZ) switches and 49 low
      crosstalk intersections. Each of the MZ switches and intersections employs
      directional couplers, which enable the composition of a low loss PILOSS switch.
      We demonstrate successful switching of digital-coherent 43-Gbps QPSK signal.

PMID- 24663709
TI  - Accuracy improvement on polymer identification using laser-induced breakdown
      spectroscopy with adjusting spectral weightings.
AB  - A new approach to polymer identification by laser-induced breakdown spectroscopy
      (LIBS) with adjusting spectral weightings (ASW) was developed in this work aiming
      at improving the identification accuracy. This approach has been achieved through
      increasing the intensities of specific characteristic spectral lines which are
      important to polymer identification but difficult to be excited. Using the ASW
      method, the identification accuracies of all 11 polymers were increased to nearly
      100%, while the accuracies of PE, PU, PP and PC were only 98%, 74%, 90% and 98%,
      respectively, without using the ASW method. 

PMID- 24663710
TI  - Waveguide-integrated microdisk light-emitting diode and photodetector based on Ge
      quantum dots.
AB  - Microdisk integrated with a bus waveguide is fabricated on silicon-on-insulator
      substrate containing Ge self-assembled quantum dots as active medium. The device
      is demonstrated to be operated as both light-emitting diode and photodetector. At
      forward bias, carriers are injected into the microdisk and light emission at 1.45
      1.6 MUm is extracted through the waveguide via microdisk-waveguide coupling.
      Sharp resonant peaks with Q-factor as high as 1350 are obtained in the
      electroluminescence spectra, corresponding to whispering gallery modes of the
      microdisk. At reverse bias, the device functions as a resonant cavity enhanced
      photodetector with wavelength-selective photo-response. The photo-current at
      resonant wavelength of 1533.65 nm is 50 times larger than that at non-resonant
      wavelength. The dark current density of the photodetector is as low as 0.29
      mA/cm2 up to -10 V bias and the peak responsivity is 5.645 mA/W.

PMID- 24663711
TI  - High spectral efficient W-band optical/wireless system employing single-sideband
      single-carrier modulation.
AB  - With broader available bandwidth, W-band wireless transmission has attracted a
      lot of interests for future Giga-bit communication. In this article, we
      experimentally demonstrate W-band radio-over-fiber (RoF) system employing single
      sideband single-carrier (SSB-SC) modulation with lower peak-to-average-power
      ratio (PAPR) than orthogonal frequency division multiplex (OFDM). To overcome the
      inter-symbol interference (ISI) of the penalty from uneven frequency response and
      SSB-SC modulation, frequency domain equalizer (FDE) and decision feedback
      equalizer (DFE) are implemented. We discuss the maximum available bandwidth of
      different modulation formats between SSB-SC and OFDM signals at the BER below
      forward error correction (FEC) threshold (3.8 * 10(-3)). Up to 50-Gbps 32-QAM SSB
      SC signals with spectral efficiency of 5 bit/s/Hz can be achieved.

PMID- 24663712
TI  - RF photonic front-end integrating with local oscillator loop.
AB  - Broadband Radio frequency (RF) photonic front-ends are one of the vital
      applications of the microwave photonics. A tunable and broadband RF photonic
      front-end integrating with the optoelectronic oscillator (OEO) based local
      oscillator has been proposed and experimentally demonstrated, in which only one
      phase modulator (PM) is employed thanks to the characteristic of the PM. The
      silicon-on-insulator based narrow-bandwidth band-pass filter is introduced for
      signal processing. The application condition of the proposed RF photonic front
      end has been discussed and the performance of the front-end has also been
      measured. The SFDR at a frequency of about 7.02 GHz is measured to be 88.6 dB
      Hz(2/3).

PMID- 24663713
TI  - Efficient source mask optimization with Zernike polynomial functions for source
      representation.
AB  - In 22nm optical lithography and beyond, source mask optimization (SMO) becomes
      vital for the continuation of advanced ArF technology node development. The pixel
      based method permits a large solution space, but involves a time-consuming
      optimization procedure because of the large number of pixel variables. In this
      paper, we introduce the Zernike polynomials as basis functions to represent the
      source patterns, and propose an improved SMO algorithm with this representation.
      The source patterns are decomposed into the weighted superposition of some well
      chosen Zernike polynomial functions, and the number of variables decreases
      significantly. We compare the computation efficiency and optimization performance
      between the proposed method and the conventional pixel-based algorithm.
      Simulation results demonstrate that the former can obtain substantial speedup of
      source optimization while improving the pattern fidelity at the same time. 

PMID- 24663714
TI  - 100-GHz DD-OFDM-RoF system over 150-km fiber transmission employing pilot-aided
      phase noise suppression and bit-loading algorithm.
AB  - This study extended the transmission distance of a 100-GHz DD-OFDM-RoF system
      through the reduction of chromatic dispersion-induced phase noise. The
      implementation of a pilot-aided phase noise suppression (PPNS) scheme enabled the
      transmission of distance-insensitive 16.97-Gbps QPSK OFDM over 0~150-km fiber and
      2-m air transmission via a DFB laser with linewidth of 1~10-MHz. We applied a bit
      loading algorithm in conjunction with PPNS to maximize spectral efficiency,
      resulting in a 93% improvement in the data rate from 11.53 to 22.27 Gbps at a
      fiber transmission of 150 km. 

PMID- 24663715
TI  - ITO DBR electrodes fabricated on PET substrate for organic electronics.
AB  - A conductive distributed Bragg reflector (DBR) fabricated on PET substrate using
      the single indium tin oxide (ITO) material is proposed. The large index contrast
      of the DBRs was obtained by depositing alternating layers of dense and porous ITO
      films. The high refractive index of the dense ITO films was achieved by long
      throw radio-frequency magnetron sputtering technique at room temperature. On the
      other hand, the porous ITO films with low refractive index were fabricated by
      supercritical CO2 (SCCO2) treatment at 60  degrees C. The index contrast of the
      dense and porous ITO films as larger as 0.59 at blue spectral range was obtained.
      For the 4.5-period ITO DBR fabricated on PET substrate, the reflectance and sheet
      resistance of 85.1% and 47 Omega/? were achieved at 475 nm.

PMID- 24663716
TI  - Higher-order modulations of fs laser pulses for GHz frequency domain photon
      migration system.
AB  - Except the fundamental modulation frequency, by higher-order-harmonic modulations
      of mode-locked laser pulses and a simple frequency demodulation circuit, a novel
      approach to GHz frequency-domain-photon-migration (FDPM) system was reported.
      With this novel approach, a wide-band modulation frequency comb is available
      without any external modulation devices and the only electronics to extract the
      optical attenuation and phase properties at a selected modulation frequency in
      FDPM systems are good mixers and lock-in devices. This approach greatly expands
      the frequency range that could be achieved by conventional FDPM systems and
      suggests that our system could extract much more information from biological
      tissues than the conventional FDPM systems. Moreover, this demonstration will be
      beneficial for discerning the minute change of tissue properties. 

PMID- 24663717
TI  - Thulium pumped mid-infrared 0.9-9MUm supercontinuum generation in concatenated
      fluoride and chalcogenide glass fibers.
AB  - We theoretically demonstrate a novel approach for generating Mid-InfraRed
      SuperContinuum (MIR SC) by using concatenated fluoride and chalcogenide glass
      fibers pumped with a standard pulsed Thulium (Tm) laser (T(FWHM)=3.5ps, P0=20kW,
      nu(R)=30MHz, and P(avg)=2W). The fluoride fiber SC is generated in 10m of ZBLAN
      spanning the 0.9-4.1MUm SC at the -30dB level. The ZBLAN fiber SC is then coupled
      into 10cm of As2Se3 chalcogenide Microstructured Optical Fiber (MOF) designed to
      have a zero-dispersion wavelength (lambda(ZDW)) significantly below the 4.1MUm
      InfraRed (IR) edge of the ZBLAN fiber SC, here 3.55MUm. This allows the MIR
      solitons in the ZBLAN fiber SC to couple into anomalous dispersion in the
      chalcogenide fiber and further redshift out to the fiber loss edge at around
      9MUm. The final 0.9-9MUm SC covers over 3 octaves in the MIR with around 15mW of
      power converted into the 6-9MUm range.

PMID- 24663718
TI  - Spatial cross modulation method using a random diffuser and phase-only spatial
      light modulator for constructing arbitrary complex fields.
AB  - We propose a spatial cross modulation method using a random diffuser and a phase
      only spatial light modulator (SLM), by which arbitrary complex-amplitude fields
      can be generated with higher spatial resolution and diffraction efficiency than
      off-axis and double-phase computer-generated holograms. Our method encodes the
      original complex object as a phase-only diffusion image by scattering the complex
      object using a random diffuser. In addition, all incoming light to the SLM is
      consumed for a single diffraction order, making a diffraction efficiency of more
      than 90% possible. This method can be applied for holographic data storage, three
      dimensional displays, and other such applications. 

PMID- 24663719
TI  - A rapid two-photon fabrication of tube array using an annular Fresnel lens.
AB  - A rapid method of fabricating microscopic tubular structures via two-photon
      polymerization is presented. Novel Fresnel lens is designed and applied to
      modulate the light field into a uniform ring pattern with controllable diameters.
      Comparing with the conventional holographic processing method, Fresnel lens shows
      higher uniformity and better flexibility, while easier to generate. This
      versatile method provides a powerful solution to produce tube structure array
      within several seconds. 

PMID- 24663720
TI  - Micro- and nanoparticle generation during nanosecond laser ablation: correlation
      between mass and optical emissions.
AB  - The particulate emission during nanosecond ablation of gold targets was
      investigated at various fluences (10-100 Jcm(-2)) and vacuum levels (0.05-750
      Torr). Atomic emission spectra were acquired during the ablation process and post
      mortem characterization of particle spatial distribution was performed using
      scanning electron microscopy. The discussion of the results in the context of
      existing theoretical models permitted the identification of four distinct mass
      removal mechanisms. While the presence, shape and intensity of atomic emission
      lines is a telltale of the nanoparticle formation process, the fluctuations of
      the emission signal over a number of laser shots was linked to the production of
      microscopic debris.

PMID- 24663721
TI  - Variation of exciton emissions of ZnO whiskers reversibly tuned by axial tensile
      strain.
AB  - Applying strain on semiconductors is a powerful method to modulate its electronic
      structures and optical properties. In this study, the behavior of liquid-nitrogen
      exciton emissions and the longitudinal optical phonon-exciton interactions of
      tensile strained [0001]-orientated ZnO whiskers were investigated using in situ
      cathodoluminescence spectroscopy. It has been found that, under the axial tensile
      strain, various exciton emissions shift to the long wavelength and their shifts
      have a linear relationship with the applied strain. This linear relationship and
      reversible shift suggest that the strain plays a dominating role in manipulating
      light emissions of axially strained ZnO whiskers. 

PMID- 24663722
TI  - Long-range surface plasmon triple-output Mach-Zehnder interferometers.
AB  - A triple-output Mach-Zehnder interferometer (MZI) operating with long-range
      surface plasmon-polariton waves, consisting of a MZI in cascade with a triple
      coupler, is demonstrated at a wavelength of ~1370 nm, using the thermo-optic
      effect to produce phase shifting. A theoretical model for three-waveguide
      coupling is also proposed and was applied to compute the transfer characteristic
      of various designs. Dimensions for the device were selected to optimize
      performance, experiments were performed, and the results were compared to theory.
      The outputs were sinusoidally related to the thermally-induced phase shift and
      separated by ~2pi/3 rad, as expected theoretically. Four detection schemes that
      take advantage of the 3 times larger dynamic range and suppress time-varying
      common perturbations are proposed and analyzed in order to improve the detection
      limit of the device. A minimum detectable phase shift ~2/3 that of a single
      output was obtained from a power difference scheme and a normalization scheme.
      The smallest minimum detectable phase shift was 7.3 mrad. The device is promising
      for sensing applications, including (bio)chemical sensing. 

PMID- 24663723
TI  - Sparse sampling for fast hyperspectral coherent anti-Stokes Raman scattering
      imaging.
AB  - We demonstrate a method to increase the acquisition speed in coherent anti-Stokes
      Raman scattering (CARS) hyperspectral imaging while retaining the relevant
      spectral information. The method first determines the important spectral
      components of a sample from a hyper-spectral image over a small number of spatial
      points but a large number of spectral points covering the accessible spectral
      range and sampling the instrument spectral resolution at the Nyquist limit. From
      these components we determine a small set of frequencies needed to retrieve the
      weights of the components with minimum error for a given measurement noise.
      Hyperspectral images with a large number of spatial points, for example covering
      a large spatial region, are then measured at this small set of frequencies, and a
      reconstruction algorithm is applied to generate the full spectral range and
      resolution. The resulting spectra are suited to retrieve from the CARS intensity
      the CARS susceptibility which is linear in the concentration, and apply
      unsupervised quantitative analysis methods such as FSC3. We demonstrate the
      method on CARS hyperspectral images of human osteosarcoma U2OS cell, with a
      reduction in the acquisition time by a factor of 25. This method is suited also
      for other coherent vibrational microscopy techniques such as stimulated Raman
      scattering, and in general for hyperspectral imaging techniques with sequential
      spectral acquisition.

PMID- 24663724
TI  - Axial super-localisation using rotating point spread functions shaped by
      polarisation-dependent phase modulation.
AB  - We present an approach for point spread function (PSF) engineering that allows
      one to shape the optical wavefront independently in both polarisation directions,
      with two adjacent phase masks displayed on a single liquid-crystal spatial light
      modulator (LC-SLM). The set-up employs a polarising beam splitter and a geometric
      image rotator to rectify and process both polarisation directions detected by the
      camera. We shape a single-lobe ("corkscrew") PSF that rotates upon defocus for
      each polarisation channel and combine the two polarisation channels with a
      relative 180 degrees  phase-shift on the computer, merging them into a single PSF
      that exhibits two lobes whose orientation contains information about the axial
      position. A major advantage lies in the possibility to measure and eliminate the
      aberrations in the two polarisation channels independently. We demonstrate axial
      super-localisation of isotropically emitting fluorescent nanoparticles. Our
      implementation of the single-lobe PSFs follows the method proposed by Prasad
      [Opt. Lett.38, 585 (2013)], and thus is to the best of our knowledge the first
      experimental realisation of this suggestion. For comparison we also study an
      approach with a rotating double-helix PSFs (in only one polarisation channel) and
      ascertain the trade-off between localisation precision and axial working range. 

PMID- 24663725
TI  - Experimental evidence of a nonlinear loss mechanism in highly doped Yb:LuAG
      crystal.
AB  - We report a rigorous study of the spectroscopic, laser and thermal properties of
      a 10at.% and a 15at.% Yb:LuAG crystals. A loss mechanism is observed in the
      medium with the highest doping, pumped at 936 nm and 968 nm, as a sharp and
      dramatic decrease of the laser output power is measured at higher excitation
      densities. The nonlinearity of the loss mechanism is confirmed by the
      fluorescence data and by the thermal lens. In particular, the dioptric power of
      the thermal lens acquired at different pumping levels shows a strong deviation of
      the expected linear trend. Here we report the influence of both the concentration
      and the ion excitation density of Yb3+ on the output powers, the slope
      efficiencies and the thresholds. Conversely excellent results are achieved with
      the 10at.%, which does not show any loss mechanism as at 1046 nm it delivers 11.8
      W with a slope efficiency of eta(s) = 82%, which is, to the best of our
      knowledge, the highest value reported in literature for this material.

PMID- 24663726
TI  - Propagation of spoof surface plasmon on metallic square lattice: bending and
      splitting of self-collimated beams.
AB  - The propagation characteristics of spoof surface plasmon modes are studied in
      both real and reciprocal spaces. From the metallic square lattice, we obtain
      constant frequency contours by directly measuring electric fields in the
      microwave frequency regime. The anisotropy of the measured constant frequency
      contour supports the presence of the negative refraction and the self-collimation
      which are confirmed from measured electric fields. Additionally, we demonstrate
      the spoof surface plasmon beam splitter in which the splitting ratio of the self
      collimated beam is controlled by varying the height of rods. 

PMID- 24663727
TI  - Experimental demonstration of DFB semiconductor lasers with varying longitudinal
      parameters.
AB  - The distributed-coupling-coefficient and distributed-coupling-coefficient
      corrugation-pitch-modulated DFB lasers are experimentally demonstrated. The
      proposed lasers maintain good side mode suppression ratio over 50dBfrom 2.5 times
      to 12.5 times threshold current. The grating profiles of varying longitudinal
      parameters are equivalently obtained by specially designed sampled Bragg gratings
      and fabricated by conventional holographic exposure and MUm-level
      photolithography. 

PMID- 24663728
TI  - Reconfigurable terahertz metamaterial device with pressure memory.
AB  - We demonstrate a liquid metal-based reconfigurable terahertz (THz) metamaterial
      device that is not only pressure driven, but also exhibits pressure memory. The
      discrete THz response is obtained by injecting eutectic gallium indium (EGaIn)
      into a microfluidic structure that is fabricated in polydimethylsiloxane (PDMS)
      using conventional soft lithography techniques. The shape of the injected EGaIn
      is mechanically stabilized by the formation of a thin oxide surface layer that
      allows the fluid to maintain its configuration within the microchannels despite
      its high intrinsic surface energy. Although the viscosity of EGaIn is twice that
      of water, the formation of the surface oxide layer prevents flow into a
      microchannel unless a critical pressure is exceeded. Using a structure in which
      the lateral channel dimensions vary, we progressively increase the applied
      pressure beyond the relevant critical pressure for each section of the device,
      enabling switching from one geometry to another (split ring resonator to closed
      ring resonator to an irregular closed ring resonator). As the geometry changes,
      the transmission spectrum of the device changes dramatically. When the external
      applied pressure is removed between device geometry changes, the liquid metal
      morphology remains unchanged, which can be regarded as a form of pressure memory.
      Once the device is fully filled with liquid metal, it can be erased through the
      use of mechanical pressure and exposure to acid vapors. 

PMID- 24663729
TI  - Generation of octave-spanning supercontinuum by Raman-assisted four-wave mixing
      in single-crystal diamond.
AB  - An octave-spanning coherent supercontinuum is generated by non-collinear Raman
      assisted four-wave mixing in single-crystal diamond using 7.7 fs laser pulses
      that have been chirped to about 420 fs in duration. The use of ultrabroad
      bandwidth pulses as input results in substantial overlap of the generated
      spectrum of the anti-Stokes sidebands, creating a phase-locked supercontinuum
      when all the sidebands are combined to overlap in time and space. The overall
      bandwidth of the generated supercontinuum is sufficient to support its
      compression to isolated few-to-single cycle attosecond transients. The
      significant spectral overlap of adjacent anti-Stokes sidebands allows the
      utilization of straight-forward spectral interferometry to test the relative
      phase coherence of the anti-Stokes outputs and is demonstrated here for two
      adjacent pairs of sidebands. The method can subsequently be employed to set the
      relative phase of the sidebands for pulse compression and for the synthesis of
      arbitrary field transients. 

PMID- 24663730
TI  - Wavelength conversion of 28 GBaud 16-QAM signals based on four-wave mixing in a
      silicon nanowire.
AB  - We demonstrate error-free wavelength conversion of 28 GBaud 16-QAM single
      polarization (112 Gb/s) signals based on four-wave mixing in a dispersion
      engineered silicon nanowire (SNW). Wavelength conversion covering the entire C
      band is achieved using a single pump. We characterize the performance of the
      wavelength converter subsystem through the electrical signal to noise ratio
      penalty as well as the bit error rate of the converted signal as a function of
      input signal power. Moreover, we evaluate the degradation of the optical signal
      to noise ratio due to wavelength conversion in the SNW. 

PMID- 24663731
TI  - Long-term stable passive synchronization between two-color mode-locked lasers
      with the aid of temperature stabilization.
AB  - We demonstrate long-term stable passive synchronization between two-color
      Ti:sapphire (master) and Yb-doped fiber (slave) mode-locked lasers in the master
      slave configuration. Active temperature stabilization suppresses the repetition
      fluctuation of the slave laser, and with the aid of temperature stabilization in
      combination with simple repetition locking of the master laser, long-term stable
      synchronization as long as 6 h was realized. The repetition rates of both lasers
      are locked in submillihertz precision. A timing jitter of 0.75 fs was obtained at
      a detection bandwidth of 350 kHz. 

PMID- 24663732
TI  - QAM quantum stream cipher using digital coherent optical transmission.
AB  - A Quantum Stream Cipher (QSC) using Quadrature Amplitude Modulation (QAM) is
      presented to greatly increase the secure degree compared with ASK or PSK/QSC. We
      propose encoding multi-bit data in one symbol with a multi-bit basis state,
      resulting in QAM/QSC, which employs amplitude and phase encryption of the light
      beam simultaneously. A 16 QAM/QSC experiment at 10 Gbit/s was successfully
      carried out over 160 km using a digital coherent optical transmission technique,
      where 16 QAM data were encrypted in a constellation with 32 * 32~4096 * 4096
      symbols. We show experimentally that the Number of Masked Signals (NMS) in the
      quantum noise Gamma(QAM) for QAM/QSC becomes a square multiple larger than
      Gamma(ASK) for ASK/QSC. Gamma(QAM) exceeds 10,000. This result indicates that the
      QSC technique is more robust against eavesdroppers than ASK or PSK/QSC.

PMID- 24663733
TI  - Spectro-angular light scattering measurements of individual microscopic objects.
AB  - The spectro-angular light scattering measurements of individual microscopic
      objects are presented. Using spectroscopic quantitative phase microscopy and
      Fourier transform light scattering, the 2D angle-resolved light scattering
      intensity and phase patterns are measured in a spectral range of 450-750 nm and
      an angular range of -70-70 degrees . The spectro-angular light scattering
      measurements of individual polystyrene beads are demonstrated with high
      sensitivity and precision. 

PMID- 24663734
TI  - Carrier transfer and thermal escape in CdTe/ZnTe quantum dots.
AB  - We report on the carrier transfer and thermal escape in CdTe/ZnTe quantum dots
      (QDs) grown on a GaAs substrate. The significant emission-energy-dependent decay
      time at high excitation intensity (35 W/cm2) is attributed to the lateral
      transfer of carriers in the QDs. At low temperature (< 35 K) and low emission
      energy (< 2.168 eV), a thermally activated transition occurs between two
      different states separated by approximately 9 meV, while the main contribution to
      nonradiative processes is the thermal escape from QDs that is assisted by carrier
      scattering via the emission of longitudinal phonons through the excited QD states
      at high temperature, with energies of approximately 19 meV.

PMID- 24663735
TI  - Coherent polarization beam combination of four mode-locked fiber MOPAs in
      picosecond regime.
AB  - In this manuscript, we report on coherent polarization beam combination (CPBC) of
      a four-channel pulsed amplifier array in the picosecond regime by using single
      frequency dithering technique. By employing a photo-detector with low-pass
      bandwidth (8.5 MHz at 10 dB gain) to filter the intensity fluctuation and obtain
      phase errors for feedback, a combined laser pulse with~480 ps pulse width at~60
      MHz repetition rate is obtained with an average power of 88 W. By adjusting the
      optical path differences (OPDs) and controlling the pump power to ensure the
      synchronizations and alleviate the influence of nonlinear phases among each
      channel, more than 90% combining efficiency is achieved with excellent beam
      quality (M(2)~1.1). Finally, the efficiency loss of the system along with the
      power scaling process is discussed.

PMID- 24663736
TI  - Grating tunable 4-14 um GaAs optical parametric oscillator pumped at 3 um.
AB  - We demonstrate a broadly and continuously tunable optical parametric oscillator
      (OPO) based on orientation-patterned GaAs (OP-GaAs) operating at 2 kHz repetition
      rate. With the choice of the pump wavelength near lambda = 3 um, we were able to
      achieve tunable output in the whole range of 4-14.2 um with a linewidth between 2
      and 6 cm(-1), using a single OP-GaAs structure with a domain reversal period of
      150 um. The OPO output was tuned using (i) an intracavity diffraction grating,
      and (ii) fine adjustment of the pump wavelength near 3 um. In certain portions of
      the spectrum this system potentially allows fast (sub-millisecond scale)
      wavelength tuning over > 2500 nm by fast steering the diffraction grating at a
      fixed pump wavelength.

PMID- 24663737
TI  - Design of a SiO2 top-cladding and compact polarization splitter-rotator based on
      a rib directional coupler.
AB  - A compact polarization splitter-rotator based on a silicon-on-insulator rib
      asymmetrical directional coupler with SiO2 top-cladding is proposed. Unlike
      previously reported PSRs which specifically required the top-cladding material to
      be different from the bottom cladding in order to break the symmetry of the
      waveguide cross-section, our proposed PSR has no such limitation on the top
      cladding due to the horizontal asymmetry of the rib waveguide. In addition, the
      device is highly compact and has a total length as short as 24 MUm. Numerical
      simulation shows that a high conversion efficiency of ~97% is obtained at the
      wavelength of 1550 nm. With the width variation of +/- 15 nm and the gap
      variation of +/- 50 nm, the PSR still has high ER of 12 dB at the cross-port,
      showing large fabrication tolerance. This device can be cascaded to improve the
      performance at the through port and an example of a two-stage PSR is presented.
      The mode conversion between the strip waveguide and the rib waveguide is also
      discussed.

PMID- 24663738
TI  - TGG ceramics based Faraday isolator with external compensation of thermally
      induced depolarization.
AB  - A Faraday isolator with compensation of thermally induced depolarization outside
      magnetic field was implemented for the first time on TGG ceramics. Stable
      isolation ratio of 38 dB in steady-state regime at a laser power of 300 W was
      demonstrated in experiment. Theoretical estimates show a feasibility of a device
      that would provide an isolation ratio higher than 30 dB up to laser power of 2kW.

PMID- 24663739
TI  - Supercontinuum generation in highly nonlinear fibers using amplified noise-like
      optical pulses.
AB  - Supercontinuum generation in a highly nonlinear fiber pumped by noise-like pulses
      from an erbium-doped fiber ring laser is investigated. To generate ultrabroad
      spectra, a fiber amplifier is used to boost the power launched into the highly
      nonlinear fiber. After amplification, not only the average power of the noise
      like pulses is enhanced but the spectrum of the pulses is also broadened due to
      nonlinear effects in the fiber amplifier. This leads to a reduction of the peak
      duration in their autocorrelation trace, suggesting a similar extent of pulse
      compression; by contrast, the pedestal duration increases only slightly,
      suggesting that the noise-like characteristic is maintained. By controlling the
      pump power of the fiber amplifier, the compression ratio of the noise-like pulse
      duration can be adjusted. Due to the pulse compression, supercontinuum generation
      with a broader spectrum is therefore feasible at a given average power level of
      the noise-like pulses launched into the highly nonlinear fiber. As a result,
      supercontinuum generation with an optical spectrum spanning from 1208 to 2111 nm
      is achieved using a 1-m nonlinear fiber pumped by amplified noise-like pulses of
      15.5 MHz repetition rate at an average power of 202 mW. 

PMID- 24663740
TI  - Recording oscillations of sub-micron size cantilevers by extreme ultraviolet
      Fourier transform holography.
AB  - We recorded the fast oscillation of sub-micron cantilevers using time-resolved
      extreme ultraviolet (EUV) Fourier transform holography. A tabletop capillary
      discharge EUV laser with a wavelength of 46.9 nm provided a large flux of
      coherent illumination that was split using a Fresnel zone plate to generate the
      object and the reference beams. The reference wave was produced by the first
      order focus while a central opening in the zone plate provided a direct
      illumination of the cantilevers. Single-shot holograms allowed for the
      composition of a movie featuring the fast oscillation. Three-dimensional
      displacements of the object were determined as well by numerical back
      propagation, or "refocusing" of the electromagnetic fields during the
      reconstruction of a single hologram. 

PMID- 24663741
TI  - Stretchable optical waveguides.
AB  - We introduce the concept of mechanically stretchable optical waveguides. The
      technology to fabricate these waveguides is based on a cost-efficient replication
      method, employing commercially available polydimethylsiloxane (PDMS) materials.
      Furthermore, VCSELs (lambda = 850 nm) and photodiodes, embedded in a flexible
      package, were integrated with the waveguides to obtain a truly bendable,
      stretchable and mechanically deformable optical link. Since these sources and
      detectors were integrated, it was possible to determine the influence of bending
      and stretching on the waveguide performance. 

PMID- 24663742
TI  - Coherence-controlled holographic microscopy in diffuse media.
AB  - Low-coherence interferometric microscopy (LCIM) enables to image through
      scattering media by filtration of ballistic light from diffuse light. The
      filtration mechanism is called coherence gating. We show that coherence
      controlled holographic microscope (CCHM), which belongs to LCIM, enables to image
      through scattering media not only with ballistic light but also with diffuse
      light. The theoretical model was created which derives the point spread function
      of CCHM for imaging through diffuse media both with ballistic and diffuse light.
      The results of the theoretical model were compared to the experimental results.
      In the experiment the resolution chart covered by a ground glass was imaged. The
      experimental results are in the good agreement with the theoretical results. It
      was shown both by experiments and the theoretical model, that with ballistic and
      diffuse light we can obtain images with diffraction limited resolution. 

PMID- 24663743
TI  - Gain-switching dynamics in optically pumped single-mode InGaN vertical-cavity
      surface-emitting lasers.
AB  - The gain-switching dynamics of single-mode pulses were studied in blue InGaN
      multiple-quantum-well vertical-cavity surface-emitting lasers (VCSELs) through
      impulsive optical pumping. We measured the shortest single-mode pulses of 6.0 ps
      in width with a method of up-conversion, and also obtained the pulse width and
      the delay time as functions of pump powers from streak-camera measurements.
      Single-mode rate-equation calculations quantitatively and consistently explained
      the observed data. The calculations indicated that the pulse width in the present
      VCSELs was mostly limited by modal gain, and suggested that subpicosecond pulses
      should be possible within feasible device parameters. 

PMID- 24663744
TI  - Measurement and modeling of microlenses fabricated on single-photon avalanche
      diode arrays for fill factor recovery.
AB  - Single-photon avalanche diode (SPAD) imagers typically have a relatively low fill
      factor, i.e. a low proportion of the pixel's surface is light sensitive, due to
      in-pixel circuitry. We present a microlens array fabricated on a 128*128 single
      photon avalanche diode (SPAD) imager to enhance its sensitivity. The benefits and
      limitations of these light concentrators are studied for low light imaging
      applications. We present a new simulation software that can be used to simulate
      microlenses' performance under different conditions and a new non-destructive
      contact-less method to estimate the height of the microlenses. Results of
      experiments and simulations are in good agreement, indicating that a gain >10 can
      be achieved for this particular sensor. 

PMID- 24663745
TI  - Reconstructing signals via stochastic resonance generated by photorefractive two
      wave mixing bistability.
AB  - Stochastic resonance is theoretically investigated in an optical bistable system,
      which consists of a unidirectional ring cavity and a photorefractive two-wave
      mixer. It is found that the output properties of stochastic resonance are mainly
      determined by the applied noise, the crystal length and the applied electric
      field. The influences of these parameters on the stochastic resonance are also
      numerically analyzed via cross-correlation, which offers general guidelines for
      the optimization of recovering noise-hidden signals. A cross-correlation gain of
      4 is obtained by optimizing these parameters. This provides a general method for
      reconstructing signals in nonlinear communications systems. 

PMID- 24663746
TI  - Balanced homodyne readout for quantum limited gravitational wave detectors.
AB  - Balanced homodyne detection is typically used to measure quantum-noise-limited
      optical beams, including squeezed states of light, at audio-band frequencies.
      Current designs of advanced gravitational wave interferometers use some type of
      homodyne readout for signal detection, in part because of its compatibility with
      the use of squeezed light. The readout scheme used in Advanced LIGO, called DC
      readout, is however not a balanced detection scheme. Instead, the local
      oscillator field, generated from a dark fringe offset, co-propagates with the
      signal field at the anti-symmetric output of the beam splitter. This article
      examines the alternative of a true balanced homodyne detection for the readout of
      gravitational wave detectors such as Advanced LIGO. Several practical advantages
      of the balanced detection scheme are described. 

PMID- 24663747
TI  - Optical damage threshold of Au nanowires in strong femtosecond laser fields.
AB  - Ultrashort, intense light pulses permit the study of nanomaterials in the optical
      non-linear regime. Non-linear regimes are often present just below the damage
      threshold thus requiring careful tuning of the laser parameters to avoid melting
      the materials. Detailed studies of the damage threshold of nanoscale materials
      are therefore needed. We present results on the damage threshold of gold (Au)
      nanowires when illuminated by intense femtosecond pulses. These nanowires were
      synthesized via the directed electrochemical nanowire assembly (DENA) process in
      two configurations: (1) free-standing Au nanowires on tungsten (W) electrodes and
      (2) Au nanowires attached to fused silica slides. In both cases the wires have a
      single-crystalline structure. For 790 nm laser pulses with durations of 108 fs
      and 32 fs at a repetition rate of 2 kHz, we find that the free-standing nanowires
      melt at intensities close to 3 TW/cm2 (194 mJ/cm2) and 7.5 TW/cm2 (144 mJ/cm2),
      respectively. The Au nanowires attached to silica slides melt at slightly higher
      intensities, just above 10 TW/cm2 (192 mJ/cm2) for 32 fs pulses. Our results can
      be explained with an electron-phonon interaction model that describes the
      absorbed laser energy and subsequent heat conduction across the wire.

PMID- 24663748
TI  - Equalizer tap length requirement for mode group delay-compensated fiber link with
      weakly random mode coupling.
AB  - The equalizer tap length requirement is investigated analytically and numerically
      for differential modal group delay (DMGD) compensated fiber link with weakly
      random mode coupling. Each span of the DMGD compensated link comprises multiple
      pairs of fibers which have opposite signs of DMGD. The result reveals that under
      weak random mode coupling, the required tap length of the equalizer is
      proportional to modal group delay of a single DMGD compensated pair, instead of
      the total modal group delay (MGD) of the entire link. By using small DMGD
      compensation step sizes, the required tap length (RTL) can be potentially reduced
      by 2 orders of magnitude. 

PMID- 24663749
TI  - The effect of the Gouy phase in optical-pump-THz-probe spectroscopy.
AB  - We show theoretically as well as experimentally that the Gouy-phase shift, which
      depends on the exact positioning of a sample in relation to the focus of a probe
      beam in a pump-probe experiment, may have a pronounced effect on the shape of the
      pump-probe signal. The effect occurs only when single-cycle probe pulses are
      used, i.e. when the slowly varying envelope approximation breaks down, while it
      disappears for multi-cycle pulses. The effect is thus most relevant in THz time
      resolved spectroscopy, where such single cycle pulses are most commonly used, but
      it should not be overlooked also in other spectral regimes when correspondingly
      short pulses are involved. 

PMID- 24663750
TI  - Temperature-insensitive frequency tripling for generating high-average power UV
      lasers.
AB  - Aimed for generating high-average power ultraviolet (UV) lasers via third
      harmonic generation (THG) consisting of frequency doubling and tripling stages,
      we numerically and experimentally demonstrate a novel frequency tripling scheme
      capable of supporting temperature-insensitive phase-matching (PM). Two cascaded
      tripling crystals, with opposite signs of the temperature derivation of phase
      mismatch, are proposed and theoretically studied for improving the temperature
      acceptance of PM. The proof-of-principle tripling experiment using two crystals
      of LBO and BBO shows that the temperature acceptance can be ~1.5 times larger
      than that of using a single tripling crystal. In addition, the phase shift caused
      by air dispersion, along with its influence on the temperature-insensitive PM,
      are also discussed. To illustrate the potential applications of proposed two
      crystal tripling design in the high-average-power regime, full numerical
      simulations for the tripling process, are implemented based on the realistic
      crystals. The demonstrated two-crystal tripling scheme may provide a promising
      route to high-average-power THG in the UV region. 

PMID- 24663751
TI  - Phase-controlled localization and directed transport in an optical bipartite
      lattice.
AB  - We investigate coherent control of a single atom interacting with an optical
      bipartite lattice via a combined high-frequency modulation. Our analytical
      results show that the quantum tunneling and dynamical localization can depend on
      phase difference between the modulation components, which leads to a different
      route for the coherent destruction of tunneling and a convenient phase-control
      method for stabilizing the system to implement the directed transport of atom.
      The similar directed transport and the phase-controlled quantum transition are
      revealed for the corresponding many-particle system. The results can be referable
      for experimentally manipulating quantum transport and transition of cold atoms in
      the tilted and shaken optical bipartite lattice or of analogical optical two-mode
      quantum beam splitter, and also can be extended to other optical and solid-state
      systems. 

PMID- 24663752
TI  - Multichannel optical filters with an ultranarrow bandwidth based on sampled
      Brillouin dynamic gratings.
AB  - We first propose a multichannel optical filter with an ultra-narrow 3-dB
      bandwidth based on sampled Brillouin dynamic gratings (SBDGs). The multichannel
      optical filter is generated when an optical pulse interfaces with an optical
      pulse train based on an ordinary stimulated Brillouin scattering (SBS) process in
      a birefringent optical fiber. Multichannel optical filter based on SBDG is
      generated with a 3-dB bandwidth from 12.5 MHz to 1 GHz. In addition, a linearly
      chirped SBDG is proposed to generate multichannel dispersion compensator with a 3
      dB bandwidth of 300 MHz and an extremely high dispersion value of 432 ns/nm. The
      proposed multichannel optical filters have important potential applications in
      the optical filtering, multichannel dispersion compensation and optical signal
      processing. 

PMID- 24663753
TI  - Enhanced spontaneous emission inside hyperbolic metamaterials.
AB  - Hyperbolic metamaterials can enhance spontaneous emission, but the radiation
      matter coupling is not optimized if the light source is placed outside such
      media. We demonstrate a 3-fold improvement of the Purcell factor over its outer
      value and a significant enlargement in bandwidth by including the emitter within
      a Si/Ag periodic multilayer metamaterial. To extract the plasmonic modes of the
      structure into the far field we implement two types of 1D grating with triangular
      and rectangular profile, obtaining a 10-fold radiative enhancement at visible
      frequencies. 

PMID- 24663754
TI  - Analysis of dimensional tolerance for an optical demultiplexer of a highly
      alignment tolerant 4 * 25 Gb/s ROSA module.
AB  - We have developed a 4 * 25 Gb/s ROSA (receiver optical sub-assembly) module for
      100G Ethernet optical transceiver. This ROSA module has very large alignment
      tolerance of more than +/- 250 um between the optical DMUX (demultiplexer) and
      four photodiodes, for the reason it has the advantage of being easily assembled.
      The large alignment tolerance can be attributed to the dimensional tolerant
      optical DMUX, which is composed of four thin film filters attached to a
      parallelogram-shaped optic block. Since it is important to define the fabrication
      specifications for the dimension of the optic block, we analyze dimensional
      tolerance for the optic block using three-dimensional simulation. This
      parallelogram-shaped optical DMUX permits length tolerance of +/- 300 um and
      angular tolerance of +/- 0.1 degrees . The fabricated optical DMUX is estimated
      to have the angular error of less than 0.09 degrees . 

PMID- 24663755
TI  - A phase demodulation method with high spatial resolution for two-dimensional
      single-shot X-ray Talbot interferometry.
AB  - A new phase demodulation approach is proposed that uses windowed Fourier
      transforms to achieve high spatial resolution in fringe pattern analysis with a
      high signal-to-noise ratio for single-shot X-ray grating-based interferometry.
      Conventionally, Fourier transforms have been used to demodulate single-fringe
      patterns, but this requires a fringe pattern with a long period to obtain an
      acceptable signal-to-noise ratio among the demodulated parameters. However, by
      controlling the signal-to-noise ratio, the spatial resolution of demodulated
      parameters is degraded below that obtained from the phase-stepping method, which
      requires several images to obtain these parameters. In this paper, we introduce
      the use of a windowed Fourier transform with a process for analyzing the
      objective spectrum in isolation from other spectra on the Fourier space to
      overcome the limitations of the Fourier transform method. It is proved that with
      suitable assumptions the objective spectrum is isolated theoretically, and the
      spatial resolution is improved by practically accepting the limitations from the
      assumptions. We demonstrate the validity of the proposed method by comparing the
      modulation transfer function of a synthetic phantom with the conventional FT
      method. The proposed method is also valid on practical data obtained by an
      experimental setup, by which it is demonstrated that a high spatial resolution
      with high signal-to-noise ratio can be achieved by our proposed method. 

PMID- 24663756
TI  - Heterogeneous trench-assisted few-mode multi-core fiber with low differential
      mode delay.
AB  - We propose a kind of heterogeneous multi-core fiber (Hetero-MCF) with trench
      assisted multi-step index few-mode core (TA-MSI-FMC) deployed inside. After
      analyzing the impact of each parameter on differential mode delay (DMD), we
      design a couple of TA-MSI-FMCs with A(eff) of 110 MUm2 for LP01 mode. DMD of each
      TA-MSI-FMC is smaller than |170| ps/km over C + L band and the total DMD can
      approach almost 0 ps/km over C + L band if we adopt DMD managed transmission line
      technique by using only one kind of Hetero-TA-FM-MCF. For such Hetero-TA-FM-MCF,
      crosstalk is about -30 dB/100km at wavelength of 1550 nm as bending radius
      becomes larger than 15 cm, core number can reach 12, a relative core multiplicity
      factor (RCMF) is 15.7, and the RCMF can even reach 26.1 if we treat
      LP<sub>11</sub> mode as two special modes thanks to the multiple-input-multiple
      output technology.

PMID- 24663757
TI  - Experimental demonstration of 30 Gb/s direct-detection optical OFDM transmission
      with blind symbol synchronisation using virtual subcarriers.
AB  - The paper investigates the performance of a blind symbol synchronisation
      technique for optical OFDM systems based on virtual subcarriers. The test-bed
      includes a real-time 16-QAM OFDM transmitter operating at a net data rate of
      30.65 Gb/s using a single OFDM band with a single FPGA-DAC subsystem and
      demonstrates transmission over 23.3 km SSMF with direct detection at a BER of 10(
      3). By comparing the performance of the proposed synchronisation scheme with that
      of the Schmidl and Cox algorithm, it was found that the two approaches achieve
      similar performance for large numbers of averaging symbols, but the performance
      of the proposed scheme degrades as the number of averaging symbols is reduced.
      The proposed technique has lower complexity and bandwidth overhead as it does not
      rely on training sequences. Consequently, it is suitable for implementation in
      high speed optical OFDM transceivers.

PMID- 24663758
TI  - Plasmonic particles set into fast orbital motion by an optical vortex beam.
AB  - We optically trap plasmonic gold particles in two dimensions and set them into
      circular motion around the optical axis using a helically phased vortex laser
      beam. The orbiting frequency of the particles reaches 86 Hz, which corresponds to
      a particle velocity of the order 1 mm per second, for an incident laser power of
      a few tens of milliwatts. The experimentally determined orbiting frequencies are
      found to be well in line with the notion that the beam carries an orbital angular
      momentum of hl per photon. 

PMID- 24663759
TI  - Giant circular dichroism enhancement and chiroptical illusion in hybrid molecule
      plasmonic nanostructures.
AB  - Recently, there are great interest in studying the interaction between chiral
      molecules and plasmonic particles, because a weak circular dichroism (CD) signal
      in the ultraviolet (UV) region from chiral molecules can be both enhanced and
      transferred to the visible wavelength range by using plasmonic particles. Thus,
      ultrasensitive probe of tiny amounts of chiral substance by CD are worth waiting
      for. Here we present another way to strongly enhance CD of chiral molecules by
      using plasmonic particle cluster, which need not transfer to the visible
      wavelength. The method to calculate CD of chiral molecules in nanosphere clusters
      has been developed by means of multiple scattering of electromagnetic multipole
      fields. Our calculated results show that 2 orders of magnitude CD enhancement in
      the UV region for chiral molecules can be realized. Such a CD enhancement is very
      sensitive to the cluster structure. The cluster structure can cause chiroptical
      illusion in which a mirror symmetry in the CD spectra of opposite enantiomeric
      molecules is broken. The correction of quantum size effect on the phenomenon has
      also been considered. Our findings open up an alternative avenue for the
      ultrasensitive detection and illusion of chiral information. 

PMID- 24663760
TI  - Narrowband photon pair source for quantum networks.
AB  - We demonstrate a compact photon pair source based on a periodically poled lithium
      niobate nonlinear crystal in a short cavity. This approach provides efficient,
      low-loss, mode selection that is compatible with standard telecommunication
      networks. Photons with a coherence time of 8.6 ns (116 MHz) are produced and
      their purity is demonstrated. A source brightness of 134 pairs (s. mW. MHz)(-1)
      is reported. The cavity parameters are chosen such that the photon pair modes
      emitted can be matched to telecom ultra dense wavelength division multiplexing (U
      DWDM) channel spacings. The high level of purity and compatibility with standard
      telecom networks is of great importance for complex quantum communication
      networks.

PMID- 24663761
TI  - Complete determination of the orientation of NV centers with radially polarized
      beams.
AB  - In this paper, we report on the precise determination of the orientation of NV
      centers by imaging with a radially polarized beam. Vectorial Debye theory is
      applied to the field in the focus of radially polarized beams to generate
      emission profiles of two orthogonal optical dipoles. By comparing features of the
      measured emission intensity patterns with simulated results, complete orientation
      determination of the NV axis is achieved. Results are corroborated by using
      established methods requiring the polarization rotation of a linearly polarized
      excitation source, and by analysis of optically detected magnetic resonance
      spectra. These results lay new ground for any application where the knowledge of
      the orientation of the NV centers is prerequisite. 

PMID- 24663762
TI  - Determination of the water vapor continuum absorption by THz-TDS and Molecular
      Response Theory.
AB  - Determination of the water vapor continuum absorption from 0.35 to 1 THz is
      reported. The THz pulses propagate though a 137 m long humidity-controlled
      chamber and are measured by THz time-domain spectroscopy (THz-TDS). The average
      relative humidity along the entire THz path is precisely obtained by measuring
      the difference between transit times of the sample and reference THz pulses to an
      accuracy of 0.1 ps. Using the measured total absorption and the calculated
      resonance line absorption with the Molecular Response Theory lineshape, based on
      physical principles and measurements, an accurate continuum absorption is
      obtained within four THz absorption windows, that agrees well with the empirical
      theory. The absorption is significantly smaller than that obtained using the van
      Vleck-Weisskopf lineshape with a 750 GHz cut-off. 

PMID- 24663763
TI  - Photo- and electro-isomerization of azobenzenes based on polymer-dispersed liquid
      crystals doped with azobenzenes and their applications.
AB  - We report the photo-isomerization and electro-isomerization effects in
      azobenzenes-doped polymer-dispersed liquid crystals during the switching of the
      liquid crystal (LC) device between transparent (cis-isomers dominant) and
      scattering states (trans-isomers dominant). The isothermal phase transition,
      which is a result of the illumination of UV light and the application of DC
      voltage, was the main mechanism to switch the LC device between transparency,
      scattering, and gray scales. This study discusses in detail the variations in the
      population of cis-isomers as functions of the period and the amplitude of the
      applied DC voltage. 

PMID- 24663764
TI  - Harnessing randomness to control the polarization of light transmitted through
      highly scattering media.
AB  - We show that the multiple scattering events taking place inside a highly
      scattering medium, in conjunction with wavefront shaping, can be used to control
      the state of polarization of the light transmitted through a highly scattering
      medium. This control is achieved by using the intensity, phase, and polarization
      changing behavior of a scattering medium captured by a vector transmission matrix
      (VTM). We use a single beam incident upon a scattering medium to measure the
      absolute value of the VTM elements, in contrast to the multiple beams required in
      our previously reported approach. Further, the phase-only spatial light modulator
      based on a low-cost (< US$600) deformable micro-mirror array used in our work
      will make similar experiments accessible to other researchers. 

PMID- 24663765
TI  - Strong excitation of emitters in an impedance matched cavity: the area theorem,
      pi-pulse and self-induced transparency.
AB  - I theoretically study the behavior of strong pulses exciting emitters inside a
      cavity. The ensemble is supposed to be inhomogeneously broadened and the cavity
      matched finding application in quantum storage of optical or RF photons. My
      analysis is based on energy and pulse area conservation rules predicting
      important distortions for specific areas. It is well supported by numerical
      simulations. I propose a qualitative interpretation in terms of slow-light. The
      analogy with the free space situation is remarkable. 

PMID- 24663766
TI  - Fast and accurate finite element analysis of large-scale three-dimensional
      photonic devices with a robust domain decomposition method.
AB  - A fast and accurate full-wave technique based on the dual-primal finite element
      tearing and interconnecting method and the second-order transmission condition is
      presented for large-scale three-dimensional photonic device simulations. The
      technique decomposes a general three-dimensional electromagnetic problem into
      smaller subdomain problems so that parallel computing can be performed on
      distributed-memory computer clusters to reduce the simulation time significantly.
      With the electric fields computed everywhere, photonic device parameters such as
      transmission and reflection coefficients are extracted. Several photonic devices,
      with simulation volumes up to 1.9*10(4) (lambda/n(avg))3 and modeled with over
      one hundred million unknowns, are simulated to demonstrate the application,
      efficiency, and capability of this technique. The simulations show good agreement
      with experimental results and in a special case with a simplified two-dimensional
      simulation.

PMID- 24663767
TI  - Optimal electromagnetic energy transmission and real-time dissipation in extended
      media.
AB  - Pulse reshaping effects that give rise to fast and slow light phenomena are
      inextricably linked to the dynamics of energy exchange between the pulse and the
      propagation medium. Energy that is dissipated from the pulse can no longer
      participate in this exchange process, but previous methods of calculating real
      time dissipation are not valid for extended propagation media. We present a
      method for calculating real-time dissipation that is valid for electromagnetic
      pulse propagation in extended media. This method allows one to divide the energy
      stored in an extended medium into the portion that can be later transmitted out
      of the medium, and that portion which must be lost to either dissipation or
      reflection. 

PMID- 24663768
TI  - All-optical logic gate operating with single wavelength.
AB  - We design scalable all-optical logic gates that operate with the same input and
      output wavelength. We demonstrated the operation by using coupled mode equations,
      and investigated the impact of input power fluctuations and fabrication errors.
      We found that a wavelength fluctuation 0.3 times greater than the resonant
      wavelength width will degrade the operation of the system. Stronger coupling
      increases the wavelength tolerance. As regards coupling coefficient fluctuation,
      we found that the system is error-free when the fabrication precision is better
      than +/- 5 nm. This study provides information on the required input power
      stability and tolerable fabrication errors of a scalable system, which moves the
      numerical study closer to practical realization. 

PMID- 24663769
TI  - Reliable LIF/Mie droplet sizing in sprays using structured laser illumination
      planar imaging.
AB  - In this article, Structured Laser Illumination Planar Imaging (SLIPI) is used in
      combination with the LIF/Mie ratio technique for extracting a reliable two
      dimensional mapping of the droplets Sauter Mean Diameter (SMD). We show that even
      for the case of a fairly dilute spray, where single scattering events are in
      majority, the conventional LIF/Mie technique still remains largely affected by
      errors introduced by multiple light scattering. To remove this unwanted light
      intensity on both the LIF and Mie images SLIPI is used prior to apply the image
      ratio. For the first time, the SLIPI LIF/Mie results are calibrated and compared
      with measurement data from Phase Doppler Interferometry (PDI). 

PMID- 24663770
TI  - Silicon photonics broadband modulation-based isolator.
AB  - We discuss an optical isolator design based on tandem phase modulators in a long
      interferometer. It provides low-loss, broadband isolation in a photonic
      integrated circuit without requiring special materials or fabrication steps. It
      was demonstrated in silicon photonics. 

PMID- 24663771
TI  - Consolidated series for efficient calculation of the reflection and transmission
      in rough multilayers.
AB  - Fresnel reflectance and transmittance coefficients of a thin film system
      consisting of an arbitrary number of layers are expressed explicitly in the form
      of a power series of Fresnel coefficients for individual boundaries and phase
      terms for the individual films. The series is based on the evaluation of all
      possible paths light can pass through the system. However, the series is written
      as consolidated, i. e. all paths corresponding to the same powers are represented
      using a single term in the series, with multiplicity which is a simple product of
      binomial coefficients. This result is used to express the normal reflectance of a
      thin film system with arbitrarily correlated randomly rough boundaries and it is
      shown that such approach can be computationally efficient in practice. 

PMID- 24663772
TI  - Improvement of emission uniformity by using micro-cone patterned PDMS film.
AB  - Micro-patterned PDMS film was fabricated and combined with LED chip on board
      (COB) package to improve the emission uniformity of LED chip. The micro scale
      patterned sapphire substrate (PSS) was used as a mold to fabricate micro-cone
      patterned PDMS (MC-PDMS) film. A strong scattering effect from this MC-PDMS film
      can be verified by the high haze ratio and the Bi-directional Transmission
      effect. The angle dependent color temperature measurement system was used to
      measure the DeltaCCT of COB with and without MC-PDMS. The measurement results
      indicate that the DeltaCCT was reduced from 1025K to 428K. This improvement can
      effectively eliminate the yellow ring effect of LED chip. This technology can be
      thus considered as a cost-effective way for the next generation of light source
      packages. 

PMID- 24663773
TI  - Theoretical analysis for the optical deformation of emulsion droplets.
AB  - We propose a theoretical framework to predict the three-dimensional shapes of
      optically deformed micron-sized emulsion droplets with ultra-low interfacial
      tension. The resulting shape and size of the droplet arises out of a balance
      between the interfacial tension and optical forces. Using an approximation of the
      laser field as a Gaussian beam, working within the Rayleigh-Gans regime and
      assuming isotropic surface energy at the oil-water interface, we numerically
      solve the resulting shape equations to elucidate the three-dimensional droplet
      geometry. We obtain a plethora of shapes as a function of the number of optical
      tweezers, their laser powers and positions, surface tension, initial droplet size
      and geometry. Experimentally, two-dimensional droplet silhouettes have been
      imaged from above, but their full side-on view has not been observed and reported
      for current optical configurations. This experimental limitation points to
      ambiguity in differentiating between droplets having the same two-dimensional
      projection but with disparate three-dimensional shapes. Our model elucidates and
      quantifies this difference for the first time. We also provide a dimensionless
      number that indicates the shape transformation (ellipsoidal to dumbbell) at a
      value ~ 1.0, obtained by balancing interfacial tension and laser forces,
      substantiated using a data collapse. 

PMID- 24663774
TI  - Graphene-based passively mode-locked bidirectional fiber ring laser.
AB  - We present an all-fiber bidirectional passively mode-locked soliton laser with a
      graphene-based saturable absorber for the first time to the best of our
      knowledge. Our design includes a four-port circulator to introduce different
      sections of cavity for the two counter-propagating pulses, so they have distinct
      output characteristics. Simultaneous bidirectional operation is achieved by
      appropriately adjusting the net cavity birefringence and loss. In the clockwise
      direction, the laser emits ~750 fs pulses at 1561.6 nm, with a repetition rate of
      7.68 MHz. In the counter clockwise direction, the central wavelength, pulse
      width, and repetition rate are 1561.0 nm, ~850 fs, and 6.90 MHz, respectively. 

PMID- 24663775
TI  - Two-mode division multiplexing in a silicon-on-insulator ring resonator.
AB  - Mode-division multiplexing (MDM) is an emerging multiple-input multiple-output
      method, utilizing multimode waveguides to increase channel numbers. In the past,
      silicon-on-insulator (SOI) devices have been primarily focused on single-mode
      waveguides. We present the design and fabrication of a two-mode SOI ring
      resonator for MDM systems. By optimizing the device parameters, we have ensured
      that each mode is treated equally within the ring. Using adiabatic Bezier curves
      in the ring bends, our ring demonstrated a signal-to-crosstalk ratio above 18 dB
      for both modes at the through and drop ports. We conclude that the ring resonator
      has the potential for filtering and switching for MDM systems on SOI. 

PMID- 24663776
TI  - Optimal light collection from diffuse sources: application to optical fibre
      coupled luminescence dosimetry.
AB  - A model is developed to evaluate the light collection of a diffuse light source
      located at the tip of an optical fibre. The model is confirmed experimentally and
      used to evaluate and compare the light collection efficiency of different fibre
      coupled luminescence dosimeter probe designs. The model includes contributions
      from both meridional and skew rays, and considers the light collection from an
      optically attenuating scintillator. Hence the model enables the optimisation of
      different, but useful and new probe materials such as BeO ceramic. Four different
      dosimeter architectures are considered, including previously investigated probe
      designs; the butt-coupled and reflective wall, along with two novel designs. The
      novel designs utilise a combination of the scintillating material and transparent
      media to increase the light collection. Simulations indicate that the novel
      probes are more efficient in light collection for applications in which it is
      necessary to minimise the volume of the scintillating material. 

PMID- 24663777
TI  - Laser beam complex amplitude measurement by phase diversity.
AB  - The control of the optical quality of a laser beam requires a complex amplitude
      measurement able to deal with strong modulus variations and potentially highly
      perturbed wavefronts. The method proposed here consists in an extension of phase
      diversity to complex amplitude measurements that is effective for highly
      perturbed beams. Named camelot for Complex Amplitude MEasurement by a Likelihood
      Optimization Tool, it relies on the acquisition and processing of few images of
      the beam section taken along the optical path. The complex amplitude of the beam
      is retrieved from the images by the minimization of a Maximum a Posteriori error
      metric between the images and a model of the beam propagation. The analytical
      formalism of the method and its experimental validation are presented. The
      modulus of the beam is compared to a measurement of the beam profile, the phase
      of the beam is compared to a conventional phase diversity estimate. The precision
      of the experimental measurements is investigated by numerical simulations. 

PMID- 24663778
TI  - Femtosecond imaging of nonlinear acoustics in gold.
AB  - We have developed a high-sensitivity, low-noise femtosecond imaging technique
      based on pump-probe time-resolved measurements with a standard CCD camera. The
      approach used in the experiment is based on lock-in acquisitions of images
      generated by a femtosecond laser probe synchronized to modulation of a
      femtosecond laser pump at the same rate. This technique allows time-resolved
      imaging of laser-excited phenomena with femtosecond time resolution. We
      illustrate the technique by time-resolved imaging of the nonlinear reshaping of a
      laser-excited picosecond acoustic pulse after propagation through a thin gold
      layer. Image analysis reveals the direct 2D visualization of the nonlinear
      acoustic propagation of the picosecond acoustic pulse. Many ultrafast pump-probe
      investigations can profit from this technique because of the wealth of
      information it provides over a typical single diode and lock-in amplifier setup,
      for example it can be used to image ultrasonic echoes in biological samples. 

PMID- 24663779
TI  - Self-bending of light in photorefractive semiconductors with hot-electron effect.
AB  - This article analyzes nonlinear light propagation in semiconductors with bipolar
      conductivity and nonlinear transport of electrons. We show how the competition
      between electron and hole conductivity can influence light propagation, leading
      to the self-bending effect of optical beam trajectory, which depending on the
      value of trap compensation coefficient may be stationary or transient. 

PMID- 24663780
TI  - Wideband generation of pulses in dual-pump optical parametric amplifier: theory
      and experiment.
AB  - The generation of pulses in dual-pump fiber optical parametric amplifier is
      investigated. Theoretically, it is shown that in an analogical manner to pulse
      generation in single-pump fiber optical parametric amplifiers, the generated
      pulse shape depends on the linear phase mismatch between the interacting waves.
      However the dual-pump architecture allows for the bounding of the phase mismatch
      over a wide bandwidth. This feature permits the generation of uniform pulses over
      a wide bandwidth, contrary to the single-pump architecture. Using the developed
      theory, a pulse source with uniform pulses at 5 GHz repetition rate and duty
      cycle of 0.265 over 40 nm is demonstrated. 

PMID- 24663781
TI  - Improvement of performance of liquid crystal microlens with polymer surface
      modification.
AB  - An electrically controllable liquid crystal (LC) microlens with polymer crater,
      which is simply prepared by droplet evaporation, has been previously proposed as
      a focusing device possessing excellent characteristics in optical performance,
      especially for the capability of tunable focal lengths. As the alignment layer on
      the crater surface cannot be effectively rubbed, non-uniformly symmetrical
      electric fields in the LC lenses usually induce disclination lines during
      operation. In this paper, a polymer surface stabilization technique is applied to
      successfully prevent disclination lines and greatly improve the performance of
      the LC microlens with the polymer crater. 

PMID- 24663782
TI  - Surface-plasmon polariton solutions at a lossy slab in a symmetric surrounding.
AB  - A rigorous theoretical formulation based on electromagnetic plane waves is
      utilized to construct a unified framework and identification of all possible
      surface-plasmon polariton solutions at an absorptive slab in a symmetric,
      lossless dielectric surrounding. In addition to the modes reported in literature,
      sets of entirely new mode solutions are presented. The corresponding fields are
      classified into different categories and examined in terms of bound and leaky
      modes, as well as forward-and backward-propagating modes, both outside and inside
      the slab. The results could benefit plasmon based applications in thin-film
      nanophotonics. 

PMID- 24663783
TI  - Experimental investigation on multi-dimensional digital predistortion for multi
      band radio-over-fiber systems.
AB  - The recently-proposed multi-dimensional digital predistortion (DPD) technique is
      experimentally investigated in terms of nonlinearity order, memory length,
      oversampling rate, digital-to-analog conversion resolution, carrier frequency
      dependence and RF input power tolerance, in both directly-modulated and
      externally-modulated multi-band radio-over-fiber (RoF) systems. Similar
      characteristics of the multi-dimensional digital predistorter are identified in
      directly-modulated and externally-modulated RoF systems. The experimental results
      suggest implementing a memory-free multi-dimensional digital predistorter
      involving nonlinearity orders up to 5 at 2 * oversampling rate for practical
      multi-band RoF systems. Using the suggested parameters, the multi-dimensional DPD
      is able to improve the RF input power tolerance by greater than 3dB for each band
      in a two-band RoF system, indicating an enhancement of RF power transmitting
      efficiency. 

PMID- 24663784
TI  - 1550-nm time-of-flight ranging system employing laser with multiple repetition
      rates for reducing the range ambiguity.
AB  - We demonstrated a time-of-flight (TOF) ranging system employing laser pulses at
      1550 nm with multiple repetition rates to decrease the range ambiguity, which was
      usually found in high-repetition TOF systems. The time-correlated single-photon
      counting technique with an InGaAs/InP avalanche photodiode based single-photon
      detector, was applied to record different arrival time of the scattered return
      photons from the non-cooperative target at different repetition rates to
      determine the measured distance, providing an effective and convenient method to
      increase the absolute range capacity of the whole system. We attained hundreds of
      meters range with millimeter accuracy by using laser pulses of approximately 10
      MHz repetition rates. 

PMID- 24663785
TI  - Dynamic stereo microscopy for studying particle sedimentation.
AB  - We demonstrate a new method for measuring the sedimentation of a single colloidal
      bead by using a combination of optical tweezers and a stereo microscope based on
      a spatial light modulator. We use optical tweezers to raise a micron-sized silica
      bead to a fixed height and then release it to observe its 3D motion while it
      sediments under gravity. This experimental procedure provides two independent
      measurements of bead diameter and a measure of Faxen's correction, where the
      motion changes due to presence of the boundary. 

PMID- 24663786
TI  - Comparative analysis of spectral coherence in microresonator frequency combs.
AB  - Microresonator combs exploit parametric oscillation and nonlinear mixing in an
      ultrahigh-Q cavity. This new comb generator offers unique potential for chip
      integration and access to high repetition rates. However, time-domain studies
      reveal an intricate spectral coherence behavior in this type of platform. In
      particular, coherent, partially coherent or incoherent combs have been observed
      using the same microresonator under different pumping conditions. In this work,
      we provide a numerical analysis of the coherence dynamics that supports the above
      experimental findings and verify particular design rules to achieve spectrally
      coherent microresonator combs. A particular emphasis is placed in understanding
      the differences between so-called Type I and Type II combs. 

PMID- 24663787
TI  - Ultra-compact 32-channel drop filter with 100 GHz spacing.
AB  - We demonstrated 32-channel drop filters with 100 GHz spacing consisting of
      arrayed nanocavities and a waveguide in a photonic crystal silicon slab. Changing
      the lattice constant of the nanocavities on the subnanometer scale successfully
      controlled the drop wavelengths at 100 GHz spacing in the wavelength range
      between 1510 and 1550 nm. The device size was as small as 15 MUm * 270 MUm, and
      the variation in drop wavelengths was less than 0.3 nm in terms of standard
      deviation. We also present a movie showing the operation of the drop filter,
      demonstrating that the arrayed nanocavities have the potential for developing
      ultracompact 100 GHz spaced filters in a dense wavelength division multiplexing
      system. 

PMID- 24663788
TI  - Optical vortex arrays from smectic liquid crystals.
AB  - We demonstrate large-area, closely-packed optical vortex arrays using self
      assembled defects in smectic liquid crystals. Self-assembled smectic liquid
      crystals in a three-dimensional torus structure are called focal conic domains.
      Each FCD, having a micro-scale feature size, produces an optical vortex with
      consistent topological charge of 2. The spiral profile in the interferometry
      confirms the formation of an optical vortex, which is predicted by Jones matrix
      calculations. 

PMID- 24663789
TI  - Experimental and numerical study of the symbolic dynamics of a modulated external
      cavity semiconductor laser.
AB  - We study the symbolic dynamics of a stochastic excitable optical system with
      periodic forcing. Specifically, we consider a directly modulated semiconductor
      laser with optical feedback in the low frequency fluctuations (LFF) regime. We
      use a method of symbolic time-series analysis that allows us to uncover serial
      correlations in the sequence of intensity dropouts. By transforming the sequence
      of inter-dropout intervals into a sequence of symbolic patterns and analyzing the
      statistics of the patterns, we unveil correlations among several consecutive
      dropouts and we identify clear changes in the dynamics as the modulation
      amplitude increases. To confirm the robustness of the observations, the
      experiments were performed using two lasers under different feedback conditions.
      Simulations of the Lang-Kobayashi (LK) model, including spontaneous emission
      noise, are found to be in good agreement with the observations, providing an
      interpretation of the correlations present in the dropout sequence as due to the
      interplay of the underlying attractor topology, the external forcing, and the
      noise that sustains the dropout events. 

PMID- 24663790
TI  - Artificial TE-mode surface waves at metal surfaces mimicking surface plasmons.
AB  - Manipulation of light in subwavelength scale can be realized with metallic
      nanostructures for TM-polarization components due to excitation of surface
      plasmons. TE-polarization components of light are usually excluded in
      subwavelength metal structures for mesoscopic optical interactions. Here we show
      that, by introducing very thin high index dielectric layers on structured metal
      surfaces, pseudo surface polarization currents can be induced near metal
      surfaces, which bring to excitation of artificial TE-mode surface waves at the
      composite meta-surfaces. This provides us a way to manipulate TE-polarized light
      in subwavelength scale. Typical properties of the artificial surface waves are
      further demonstrate for their excitation, propagation, optical transmission, and
      enhancement and resonances of the localized fields, mimicking those of surface
      plasmon waves. 

PMID- 24663791
TI  - How to avoid a negative shift in reflection-type surface plasmon resonance
      biosensors with metallic nanostructures.
AB  - We experimentally demonstrate that introduction of a dielectric film can prevent
      the surface plasmon resonance (SPR) curve from being shifted to a smaller angle,
      called negative shift, which occurs unpredictably when metallic nanostructures
      deposited on a metal film are exposed to an adsorption of binding analytes. From
      parylene coating experiments, we find that the proposed reflection-type SPR
      system with a low refractive index MgF2 film and gold nanorods can provide an
      enhanced sensitivity by more than 6 times as well as a reliable positive shift.
      It is due to the fact that use of a dielectric film can contribute to the
      compensation of an anomalous dispersion relation and the prevention of a
      destructive interaction of propagating surface plasmons with multiple localized
      plasmon modes. Our approach is intended to show the feasibility and extend the
      applicability of the proposed SPR system to diverse biomolecular reactions.

PMID- 24663792
TI  - Pr and F co-doped SnO2 transparent conductive films with high work function
      deposited by ion-assisted electron beam evaporation.
AB  - A transparent conductive oxide (TCO) Pr and F co-doped SnO2 (PFTO) film is
      prepared by ion-assisted electron beam deposition. An optimized PFTO film shows a
      high average visible optical transmittance of 83.6% and a minimum electrical
      resistivity of 3.7 * 10(-3) Omega.cm corresponding to a carrier density of 1.298
      * 10(20) cm(-3) and Hall mobility of 12.99 cm(2)/V?s. This PFTO film shows a high
      work function of 5.147 eV and favorable surface morphology with an average
      roughness of 1.45 nm. Praseodymium fluoride is found to be an effective material
      to dope F into SnO2 that can simplify the fabrication process of SnO2-based TCO
      films.

PMID- 24663793
TI  - Generalized phase-shifting algorithm for inhomogeneous phase shift and spatio
      temporal fringe visibility variation.
AB  - A cascade least-squares scheme for wrapped phase extraction using two or more
      phase-shifted fringe-patterns with unknown and inhomogeneous surface phase shift
      is proposed. This algorithm is based on the parameter estimation approach to
      process fringe-patterns where, except for the interest phase distribution that is
      a function of the space only, all other parameters are functions of both space
      and time. Computer simulations and experimental results show that phase computing
      is possible even when an inhomogeneous phase shift is induced by nonlinearity of
      the piezoelectric materials or miscalibrated phase shifters. The algorithm's
      features and its operating conditions will been discussed. Due to the useful
      properties of this algorithm such as the robustness, computational efficiency,
      and user-free execution, this proposal could be used in automatic applications. 

PMID- 24663794
TI  - Investigation of designated eye position and viewing zone for a two-view
      autostereoscopic display.
AB  - Designated eye position (DEP) and viewing zone (VZ) are important optical
      parameters for designing a two-view autostereoscopic display. Although much
      research has been done to date, little empirical evidence has been found to
      establish a direct relationship between design and measurement. More rigorous
      studies and verifications to investigate DEP and to ascertain the VZ criterion
      will be valuable. We propose evaluation metrics based on equivalent luminance
      (EL) and binocular luminance (BL) to figure out DEP and VZ for a two-view
      autostereoscopic display. Simulation and experimental results prove that our
      proposed evaluation metrics can be used to find the DEP and VZ accurately. 

PMID- 24663795
TI  - Volumetric imaging of turbulent reactive flows at kHz based on computed
      tomography.
AB  - Diagnostics with three-dimensional (3D) spatial resolution and rapid temporal
      resolution have been long desired to resolve the complicated turbulence-chemistry
      interactions. This paper describes a method based on based on tomographic
      chemiluminescence (TC) to address this diagnostic need. The TC technique used
      multiple cameras to simultaneously record CH* chemiluminescence emitted by
      turbulent flames from different view angles. A 3D tomographic algorithm was then
      applied to reconstruct the instantaneous flame structures volumetrically. Both
      experimental and computational studies have been conducted to demonstrate and
      validate the 3D measurements. Experimental results were obtained instantaneously
      at kHz temporal rate, in a volume of 16 * 16 * 16 cm3, and with a spatial
      resolution estimated to be 2~3 mm. Computations were conducted to simulate the
      experimental conditions for comparison and validation.

PMID- 24663796
TI  - Sub-1 dB/cm submicrometer-scale amorphous silicon waveguide for backend on-chip
      optical interconnect.
AB  - We demonstrate a submicrometer-scale hydrogenated amorphous silicon (a-Si:H)
      waveguide with a record low propagation loss of 0.60 +/- 0.02 dB/cm because of
      the very low infrared optical absorption of our low defect a-Si:H film, the
      optimized waveguide structure and the fabrication process. The waveguide has a
      core with a thickness of 440 nm and a width of 780 nm that underlies a 100-nm
      thick ridge structure, and is fabricated by low-cost i-line stepper
      photolithography and with low-temperature processing at less than 350 degrees C,
      making it compatible with the backend process of complementary metal oxide
      semiconductor (CMOS) fabrication. 

PMID- 24663797
TI  - Efficiency vs. multi-photon contribution test for quantum dots.
AB  - The development of linear quantum computing within integrated circuits demands
      high quality semiconductor single photon sources. In particular, for a reliable
      single photon source it is not sufficient to have a low multi-photon component,
      but also to possess high efficiency. We investigate the photon statistics of the
      emission from a single quantum dot with a method that is able to sensitively
      detect the trade-off between the efficiency and the multi-photon contribution.
      Our measurements show, that the light emitted from the quantum dot when it is
      resonantly excited possess a very low multi-photon content. Additionally, we
      demonstrated, for the first time, the non-Gaussian nature of the quantum state
      emitted from a single quantum dot. 

PMID- 24663798
TI  - Inverse diffraction grating of Maxwell's equations in biperiodic structures.
AB  - Consider a time-harmonic electromagnetic plane wave incident on a perfectly
      conducting biperiodic surface (crossed grating). The diffraction is modeled as a
      boundary value problem for the three-dimensional Maxwell equation. The surface is
      assumed to be a small and smooth deformation of a planar surface. In this paper,
      a novel approach is developed to solve the inverse diffraction grating problem in
      the near-field regime, which is to reconstruct the surface with resolution beyond
      Rayleigh's criterion. The method requires only a single incident field with one
      polarization, one frequency, and one incident direction, and is realized by using
      the fast Fourier transform. Numerical results show that the method is simple,
      efficient, and stable to reconstruct biperiodic surfaces with subwavelength
      resolution. 

PMID- 24663799
TI  - Nonlocal optical properties in periodic lattice of graphene layers.
AB  - Based on the effective medium model, nonlocal optical properties in periodic
      lattice of graphene layers with the period much less than the wavelength are
      investigated. Strong nonlocal effects are found in a broad frequency range for TM
      polarization, where the effective permittivity tensor exhibits the Lorentzian
      resonance. The resonance frequency varies with the wave vector and coincides well
      with the polaritonic mode. Nonlocal features are manifest on the emergence of
      additional wave and the occurrence of negative refraction. By examining the
      characters of the eigenmode, the nonlocal optical properties are attributed to
      the excitation of plasmons on the graphene surfaces. 

PMID- 24663800
TI  - Noise statistics of phase-resolved optical coherence tomography imaging: single
      and dual-beam-scan Doppler optical coherence tomography.
AB  - Noise statistics of phase-resolved optical coherence tomography (OCT) imaging are
      complicated and involve noises of OCT, correlation of signals, and speckles. In
      this paper, the statistical properties of phase shift between two OCT signals
      that contain additive random noises and speckle noises are presented.
      Experimental results obtained with a scattering tissue phantom are in good
      agreement with theoretical predictions. The performances of the dual-beam method
      and conventional single-beam method are compared. As expected, phase shift noise
      in the case of the dual-beam-scan method is less than that for the single-beam
      method when the transversal sampling step is large. 

PMID- 24663801
TI  - Optical image encryption and hiding based on a modified Mach-Zehnder
      interferometer.
AB  - A method for optical image hiding and for optical image encryption and hiding in
      the Fresnel domain via completely optical means is proposed, which encodes
      original object image into the encrypted image and then embeds it into host image
      in our modified Mach-Zehnder interferometer architecture. The modified Mach
      Zehnder interferometer not only provides phase shifts to record complex amplitude
      of final encrypted object image on CCD plane but also introduces host image into
      reference path of the interferometer to hide it. The final encrypted object image
      is registered as interference patterns, which resemble a Fresnel diffraction
      pattern of the host image, and thus the secure information is imperceptible to
      unauthorized receivers. The method can simultaneously realize image encryption
      and image hiding at a high speed in pure optical system. The validity of the
      method and its robustness against some common attacks are investigated by
      numerical simulations and experiments. 

PMID- 24663802
TI  - Spatial normalization of ultrahigh resolution 7 T magnetic resonance imaging data
      of the postmortem human subthalamic nucleus: a multistage approach.
AB  - In this paper, we describe a novel processing strategy for the spatial
      normalization of ultrahigh resolution magnetic resonance imaging (MRI) data of
      small ex vivo samples into MNI standard space. We present a multistage scanning
      and registration method for data of the subthalamic nucleus (STN) obtained using
      ultrahigh 7 T MRI on four human postmortem brain samples. Four whole brains were
      obtained and subjected to multistage MRI scanning, corresponding to four
      different brain dissection stages. Data sets were acquired with an isotropic
      resolution of 100 MUm enabling accurate manual segmentation of the STN. Spatial
      normalization to MNI reference space was performed, probability maps were
      calculated, and results were cross-checked with an independent in vivo dataset
      showing significant overlay. Normalization of results obtained from small tissue
      samples into MNI standard space will facilitate comparison between individual
      subjects, as well as between studies. When combining ultrahigh resolution MRI of
      ex vivo samples with histological studies via blockface imaging, our method
      enables further insight and inference as multimodal data can be compared within
      the same reference space. This novel technique may be of value for research
      purposes using functional MRI techniques, and in the future may be of assistance
      for anatomical orientation in clinical practice.

PMID- 24663803
TI  - Erratum to: Expression patterns of c-Fos early gene and phosphorylated ERK in the
      rat brain following 1-h immobilization stress: concomitant changes induced in
      association with stress-related sleep rebound.

PMID- 24663804
TI  - Evaluation of a novel dog adoption program in two US communities.
AB  - Millions of dogs enter animal welfare organizations every year and only a
      fraction of them are adopted. Despite the most recent American Pet Products
      Association (APPA) data that nearly half the US population owns a dog, only 20%
      acquired their dog from an animal welfare organization. Studies show that people
      consider adopting from an animal shelter more often than they actually do, which
      indicates a potential market increase if programs can make shelter dogs more
      visible to adopters. This research focused on a novel adoption program where
      shelter dogs were transferred into foster homes who were tasked with finding an
      adopter. Shelter dogs were placed in the path of potential adopters and bypassed
      the need for the adopter to go to the shelter. The results show that this novel
      program was effective in a variety of ways including getting dogs adopted.
      Although length of stay was significantly longer for dogs in the program, the
      dogs were in a home environment, not taking up kennel space in the shelter. The
      program also had a lower rate of returns than dogs adopted at the shelter. The
      foster program tapped adopters in different geographical segments of the
      community than the dogs adopted from the shelter. By bringing shelter dogs to
      where adopters spend their time (ex: restaurants, parks, hair salons), the
      program potentially captured a segment of the population who might have obtained
      their dog from other sources besides the shelter (such as breeders or pet
      stores). This novel approach can be an effective method for adoption, has many
      benefits for shelters, and can tap into a new adopter market by engaging their
      community in a new way. 

PMID- 24663805
TI  - Mathematical modeling of calcium waves induced by mechanical stimulation in
      keratinocytes.
AB  - Recent studies have shown that the behavior of calcium in the epidermis is
      closely related to the conditions of the skin, especially the differentiation of
      the epidermal keratinocytes and the permeability barrier function, and therefore
      a correct understanding of the calcium dynamics is important in explaining
      epidermal homeostasis. Here we report on experimental observations of in vitro
      calcium waves in keratinocytes induced by mechanical stimulation, and present a
      mathematical model that can describe the experimentally observed wave behavior
      that includes finite-range wave propagation and a ring-shaped pattern. A
      mechanism of the ring formation hypothesized by our model may be related to
      similar calcium propagation patterns observed during the wound healing process in
      the epidermis. We discuss a possible extension of our model that may serve as a
      tool for investigating the mechanisms of various skin diseases. 

PMID- 24663806
TI  - In vivo imaging of mGluR5 changes during epileptogenesis using [11C]ABP688 PET in
      pilocarpine-induced epilepsy rat model.
AB  - INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) that regulates
      glutamatergic neurotransmission contributes to pathophysiology of epilepsy. In
      this study, we monitored the changes of mGluR5 in vivo using [11C]ABP688 PET
      during the epileptogenesis in a pilocarpine-induced epilepsy rat model. METHODS:
      In vivo mGluR5 images were acquired using [11C]ABP688 microPET/CT in pilocarpine
      induced chronic epilepsy rat models and controls. We also acquired microPET/CT at
      acute, subacute as well as chronic periods after status epilepticus. Non
      displaceable binding potential (BPND) of [11C]ABP688 was calculated using
      simplified reference tissue model in a voxel-based manner. mGluR5 BPND of the rat
      brains of epilepsy models and controls were compared. RESULTS: Status epilepticus
      developed after pilocarpine administration and was followed by recurrent
      spontaneous seizures for more than 3 weeks. In chronic epilepsy rat model, BPND
      in hippocampus and amygdala was reduced on a voxel-based analysis. Temporal
      changes of mGluR5 BPND was also found. In acute period after status epilepticus,
      mGluR5 BPND was reduced in the whole brain. BPND of caudate-putamen was restored
      in subacute period, while BPND of the rest of the brain was still lower. In
      chronic period, global BPND was normalized except in hippocampus and amygdala.
      CONCLUSIONS: In vivo imaging of mGluR5 using [11C]ABP688 microPET/CT could
      successfully reveal the regional changes of mGluR5 binding potential of the rat
      brain in a pilocarpine-induced epilepsy model. The temporal and spatial changes
      in mGluR5 availability suggest [11C]ABP688 PET imaging in epilepsy provide
      abnormal glutamatergic network during epileptogenesis.

PMID- 24663807
TI  - GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and
      regulates somatostatin secretion from murine islets of Langerhans.
AB  - AIMS/HYPOTHESIS: The NEFA-responsive G-protein coupled receptor 120 (GPR120) has
      been implicated in the regulation of inflammation, in the control of incretin
      secretion and as a predisposing factor influencing the development of type 2
      diabetes by regulation of islet cell apoptosis. However, there is still
      considerable controversy about the tissue distribution of GPR120 and, in
      particular, it remains unclear which islet cell types express this molecule. In
      the present study, we have addressed this issue by constructing a Gpr120
      knockout/beta-galactosidase (LacZ) knock-in (KO/KI) mouse to examine the
      distribution and functional role of GPR120 in the endocrine pancreas. METHODS: A
      KO/KI mouse was generated in which exon 1 of the Gpr120 gene (also known as
      Ffar4) was replaced in frame by LacZ, thereby allowing for regulated expression
      of beta-galactosidase under the control of the endogenous GPR120 promoter. The
      distribution of GPR120 was inferred from expression studies detecting beta
      galactosidase activity and protein production. Islet hormone secretion was
      measured from isolated mouse islets treated with selective GPR120 agonists.
      RESULTS: beta-galactosidase activity was detected as a surrogate for GPR120
      expression exclusively in a small population of islet endocrine cells located
      peripherally within the islet mantle. Immunofluorescence analysis revealed co
      localisation with somatostatin suggesting that GPR120 is preferentially produced
      in islet delta cells. In confirmation of this, glucose-induced somatostatin
      secretion was inhibited by a range of selective GPR120 agonists. This response
      was lost in GPR120-knockout mice. CONCLUSIONS/INTERPRETATION: The results imply
      that GPR120 is selectively present within the delta cells of murine islets and
      that it regulates somatostatin secretion.

PMID- 24663809
TI  - Risk of renal disease in patients with both type 1 diabetes and coeliac disease.
AB  - AIMS/HYPOTHESIS: Our aim was to study the risk of renal disease in patients with
      type 1 diabetes (T1D) and coexisting coeliac disease (CD). METHODS: Individuals
      with T1D were defined as having a diagnosis of diabetes recorded at <=30 years of
      age in the Swedish Patient Register between 1964 and 2009. Individuals with CD
      were identified through biopsy reports with villous atrophy (Marsh stage 3) from
      28 pathology departments in Sweden between 1969 and 2008. We identified 954
      patients with both T1D and CD. For each patient with T1D + CD, we selected five
      age- and sex-matched reference individuals with T1D only (n = 4,579). Cox
      regression was used to estimate the following risks: (1) chronic renal disease
      and (2) end-stage renal disease in patients with CD + T1D compared with T1D
      patients only. RESULTS: Forty-one (4.3%) patients with CD + T1D and 143 (3.1%)
      patients with T1D only developed chronic renal disease. This corresponded to an
      HR of 1.43 for chronic renal disease (95% CI 0.94, 2.17) in patients with CD +
      T1D compared with T1D only. In addition, for end-stage renal disease there was a
      positive (albeit statistically non-significant) HR of 2.54 (95% CI 0.45, 14.2).
      For chronic renal disease, the excess risk was more pronounced after >10 years of
      CD (HR 2.03, 95% CI 1.08, 3.79). Risk estimates were similar when we restricted
      our cohort to the following T1D patients: (1) those who had an inpatient
      diagnosis of T1D; (2) those who had never received oral glucose-lowering
      medication; and (3) those who had not received their first diabetes diagnosis
      during pregnancy. CONCLUSIONS/INTERPRETATION: Overall this study found no excess
      risk of chronic renal disease in patients with T1D and CD. However, in a
      subanalysis we noted a positive association between longstanding CD and chronic
      renal disease in T1D.

PMID- 24663810
TI  - DNA-functionalized hydrogels for confined membrane-free in vitro
      transcription/translation.
AB  - We microfluidically fabricate bio-orthogonal DNA-functionalized porous hydrogels
      from hyaluronic acid that are employed in in vitro transcription/translation
      (IVTT) of a green fluorescent protein. By co-encapsulating individual hydrogel
      particles and the IVTT machinery in water-in-oil microdroplets, we study protein
      expression in a defined reaction volume. Our approach enables precise control
      over protein expression rates by gene dosage. We show that gene transcription and
      translation are confined to the membrane-free hydrogel matrix, which contributes
      to the design of membrane-free protocells. 

PMID- 24663808
TI  - A serum 25-hydroxyvitamin D concentration-associated genetic variant in DHCR7
      interacts with type 2 diabetes status to influence subclinical atherosclerosis
      (measured by carotid intima-media thickness).
AB  - AIMS/HYPOTHESIS: The findings of studies investigating whether or not low serum
      25-hydroxyvitamin D [25(OH)D] concentration promotes development of
      atherosclerosis have been contradictory. The present study employed a Mendelian
      randomisation approach and carotid artery intima-media thickness (cIMT), a
      surrogate marker of coronary artery disease, to address this question. METHODS:
      The multicentre, longitudinal Carotid Intima-Media Thickness and IMT-Progression
      as Predictors of Vascular Events in a High-Risk European Population (IMPROVE)
      cohort study, which enrolled individuals with at least three cardiovascular risk
      factors and no history or symptoms of cardiovascular disease, was used for the
      present investigation. Participants underwent carotid ultrasound examination at
      baseline and at months 15 and 30. Six single nucleotide polymorphisms (SNPs)
      associated with serum 25(OH)D concentration in genome-wide association studies
      were identified and genotyped in 3,418 individuals, of whom 929 had type 2
      diabetes. RESULTS: SNPs in the genes encoding vitamin D binding protein (GC;
      rs2282679 and rs7041) and 7-dehydrocholesterol reductase/NAD synthetase-1 (DHCR7;
      rs12785878 and rs3829251) were negatively associated with 25(OH)D levels. Effect
      sizes and significance of associations between SNPs and 25(OH)D levels differed
      between individuals with and without type 2 diabetes, although no significant
      interactions were observed. A SNP in DHCR7 interacted with type 2 diabetes to
      significantly influence progression of cIMT measures independent of 25(OH)D
      levels and established risk factors. Expression analysis demonstrated that this
      SNP modulates DHCR7 mRNA levels in aortic adventitia. CONCLUSIONS/INTERPRETATION:
      SNPs in GC and DHCR7 were associated with serum levels of 25(OH)D, but only
      rs3829251 (DHCR7) influenced progression of subclinical atherosclerosis, as
      measured by cIMT, in a manner dependent on type 2 diabetes status but independent
      of 25(OH)D levels.

PMID- 24663811
TI  - Restrictive expression of acid-sensing ion channel 5 (asic5) in unipolar brush
      cells of the vestibulocerebellum.
AB  - Acid-sensing ion channels (Asic) are ligand-gated ion channels in the
      Degenerin/Epithelial Na+ channel (Deg/ENaC) family. Asic proteins are richly
      expressed in mammalian neurons. Mammals express five Asic genes: Asic1-5. The
      gene product of Asic5 is an orphan member of the family about which little is
      known. To investigate Asic5 expression, we created an Asic5 reporter mouse. We
      find that Asic5 is chiefly expressed in the brain in the cerebellum, specifically
      in the ventral uvula and nodulus of the vestibulocerebellum. Here, Asic5 is
      restrictively expressed in a subset of interneurons in the granular layer. The
      locale, distinctive shape and immunohistochemical properties of these Asic5
      expressing interneurons identify them as unipolar brush cells (UBC). Asic5 is
      richly expressed in a subset of UBCs that also express the metabotropic glutamate
      receptor 1alpha (mGluR1alpha) but not those that express calretinin. Results from
      single cell RT-PCR and electrophysiological examination of these cells are
      consistent with this identity. Such observations are consistent with Asic5
      playing a key role in the physiology of UBCs and in the function of the
      vestibulocerebellum. 

PMID- 24663812
TI  - Escalation with overdose control using time to toxicity for cancer phase I
      clinical trials.
AB  - Escalation with overdose control (EWOC) is a Bayesian adaptive phase I clinical
      trial design that produces consistent sequences of doses while controlling the
      probability that patients are overdosed. However, this design does not take
      explicitly into account the time it takes for a patient to exhibit dose limiting
      toxicity (DLT) since the occurrence of DLT is ascertained within a predetermined
      window of time. Models to estimate the Maximum Tolerated Dose (MTD) that use the
      exact time when the DLT occurs are expected to be more precise than those where
      the variable of interest is categorized as presence or absence of DLT, given that
      information is lost in the process of categorization of the variable. We develop
      a class of parametric models for time to toxicity data in order to estimate the
      MTD efficiently, and present extensive simulations showing that the method has
      good design operating characteristics relative to the original EWOC and a version
      of time to event EWOC (TITE-EWOC) which allocates weights to account for the time
      it takes for a patient to exhibit DLT. The methodology is exemplified by a cancer
      phase I clinical trial we designed in order to estimate the MTD of Veliparib (ABT
      888) in combination with fixed doses of gemcitabine and intensity modulated
      radiation therapy in patients with locally advanced, un-resectable pancreatic
      cancer. 

PMID- 24663813
TI  - Probiotics reduce mutans streptococci counts in humans: a systematic review and
      meta-analysis.
AB  - OBJECTIVES: Systematically review the available literature regarding the caries
      preventive effect of probiotics. DATA, SOURCES AND STUDY SELECTION: An electronic
      search was conducted in three databases (PubMed MEDLINE, ISI Web of Science and
      Cochrane Library) to identify all suitable studies. The outcomes had to be
      presented as the effect of probiotics on the incidence of caries or on the levels
      of mutans streptococci and/or Lactobacillus species. Human studies, written in
      English, with at least 15 participants, comparing a probiotic product with a
      placebo/no probiotic were included. Where possible, a meta-analysis was performed
      to obtain quantitative data. RESULTS: Since only two articles presented useful
      data on the caries incidence, we focused on the surrogate endpoints: mutans
      streptococci and/or Lactobacillus counts. The meta-analysis showed that when the
      probiotic and control group are compared after treatment, significantly more
      patients in the probiotic group had low mutans streptococci (<10(5) CFU/ml)
      counts and significantly less patients had high (>10(6) CFU/ml) counts. Regarding
      the Lactobacillus counts, comparing the probiotic and control group at the end of
      the probiotic use, no significant differences could be observed, neither in low
      (<10(4) CFU/ml) nor in high Lactobacillus (>10(6) CFU/ml) counts. CONCLUSIONS:
      Within the limitations of the available data, it may be concluded that probiotics
      decrease the mutans streptococci counts. This suggests that probiotics could have
      a positive effect in the prevention of caries. CLINICAL RELEVANCE: There is
      insufficient evidence that probiotics can prevent caries, but they can reduce the
      mutans streptococci counts.

PMID- 24663814
TI  - Effects of short-term xylitol gum chewing on the oral microbiome.
AB  - OBJECTIVES: The aim of this study was to determine the effects of short-term
      xylitol gum chewing on the salivary microbiota of children. MATERIALS AND
      METHODS: The study was a randomised, controlled, double-blind trial. Healthy
      children used xylitol chewing gum (xylitol group, n = 35) or sorbitol chewing gum
      (control group, n = 38) for 5 weeks. The daily dose of xylitol/sorbitol was
      approximately 6 g/day. At baseline and at the end of the test period,
      unstimulated and paraffin-stimulated saliva were collected. The microbial
      composition of the saliva was assessed using human oral microbe identification
      microarray (HOMIM). Mutans streptococci (MS) were plate cultured. RESULTS: As
      judged by HOMIM results, no xylitol-induced changes in the salivary microbiota
      took place in the xylitol group. In the control group, Veillonella atypica showed
      a significant decrease (p = 0.0001). The xylitol gum chewing decreased viable
      counts of MS in both stimulated (p = 0.006) and unstimulated (p = 0.002) saliva,
      but similar effects were also seen in the control group. CONCLUSIONS: The use of
      xylitol gum decreased MS, in general, but did not change the salivary microbial
      composition. CLINICAL RELEVANCE: Short-term consumption of xylitol had no impact
      on the composition of the salivary microbiota, but resulted in a decrease in the
      levels of MS.

PMID- 24663815
TI  - Screening for cognitive impairment in older adults: U.S. Preventive Services Task
      Force recommendation statement.
AB  - DESCRIPTION: Update of the 2003 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for dementia. METHODS: The USPSTF reviewed the
      evidence on the benefits, harms, and sensitivity and specificity of screening
      instruments for cognitive impairment in older adults and the benefits and harms
      of commonly used treatment and management options for older adults with mild
      cognitive impairment or early dementia and their caregivers. POPULATION: This
      recommendation applies to universal screening with formal screening instruments
      in community-dwelling adults in the general primary care population who are older
      than 65 years and have no signs or symptoms of cognitive impairment.
      RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to
      assess the balance of benefits and harms of screening for cognitive impairment.
      (I statement).

PMID- 24663819
TI  - Macroporous carbon decorated with dendritic platinum nanoparticles: one-step
      synthesis and electrocatalytic properties.
AB  - Macroporous carbon (MPC) with high pore accessibility and electrical conductivity
      is of great interest to the electrochemical platform. The development of a simple
      and efficient route for the direct synthesis of dendritic platinum nanoparticle
      (DPN) decorated MPC (DPN/MPC) is an interesting challenge, which is highly
      valuable for electrocatalytic applications. In this study, we propose a very
      simple route for the one-step synthesis of DPN/MPC in aqueous solution at room
      temperature without the need for any kind of seed and surfactant to direct the
      dendritic growth of Pt nanoparticles, which is performed by simply mixing an
      aqueous solution of K2PtCl4 with MPC and formic acid. The as-prepared DPN/MPC
      shows high electrocatalytic activities toward the oxidation of methanol and
      glucose. 

PMID- 24663817
TI  - Rad4 mainly functions in Chk1-mediated DNA damage checkpoint pathway as a
      scaffold protein in the fission yeast Schizosaccharomyces pombe.
AB  - Rad4/Cut5 is a scaffold protein in the Chk1-mediated DNA damage checkpoint in S.
      pombe. However, whether it contains a robust ATR-activation domain (AAD) required
      for checkpoint signaling like its orthologs TopBP1 in humans and Dpb11 in budding
      yeast has been incompletely clear. To identify the putative AAD in Rad4, we
      carried out an extensive genetic screen looking for novel mutants with an
      enhanced sensitivity to replication stress or DNA damage in which the function of
      the AAD can be eliminated by the mutations. Two new mutations near the N-terminus
      were identified that caused significantly higher sensitivities to DNA damage or
      chronic replication stress than all previously reported mutants, suggesting that
      most of the checkpoint function of the protein is eliminated. However, these
      mutations did not affect the activation of Rad3 (ATR in humans) yet eliminated
      the scaffolding function of the protein required for the activation of Chk1.
      Several mutations were also identified in or near the recently reported AAD in
      the C-terminus of Rad4. However, all mutations in the C-terminus only slightly
      sensitized the cells to DNA damage. Interestingly, a mutant lacking the whole C
      terminus was found resistant to DNA damage and replication stress almost like the
      wild type cells. Consistent with the resistance, all known Rad3 dependent
      phosphorylations of checkpoint proteins remained intact in the C-terminal
      deletion mutant, indicating that unlike that in Dpb11, the C-terminus of Rad4
      does not contain a robust AAD. These results, together with those from the
      biochemical studies, show that Rad4 mainly functions as a scaffold protein in the
      Chk1, not the Cds1(CHK2 in humans), checkpoint pathway. It plays a minor role or
      is functionally redundant with an unknown factor in Rad3 activation. 

PMID- 24663818
TI  - Nasal carriage of Staphylococcus aureus in Botucatu, Brazil: a population-based
      survey.
AB  - Recent increases in the incidence and severity of staphylococcal infections
      renewed interest in studies that assess the burden of asymptomatic carriage of
      Staphylococcus aureus in the community setting. We conducted a population-based
      survey in the city of Botucatu, Brazil (122,000 inhabitants), in order to
      identify the prevalence of nasal carriage of Staphylococcus aureus (including
      methicillin-resistant strains). Nasal swabs were obtained from 686 persons over
      one year of age. Resistance to methicillin was assessed through phenotypic
      methods, identification of the mecA gene and typing of the Staphylococcal
      Chromosome Cassette mec (SCCmec). Methicillin-resistant S. aureus (MRSA) isolates
      were characterized using Pulsed-Field Gel Electrophoresis (PFGE), Multilocus
      Sequence Typing (MLST) and spa typing. Polymerase chain reaction was applied to
      identify genes coding for Panton-Valentine Leukocidin (PVL) in isolates. The
      prevalence of overall S. aureus carriage was 32.7% (95%CI, 29.2%-36.2%). Carriers
      were significantly younger (mean age, 28.1 versus 36.3 for non-carriers; OR for
      age, 0.98; 95%CI, 0.97-0.99) and likely to report recent skin infection (OR,
      1.85; 95%CI, 1.03-3.34). Carriage of methicillin-resistant S. aureus (MRSA) was
      found in 0.9% of study subjects (95%CI, 0.4%-1.8%). All MRSA isolates harbored
      SCCmec type IV, and belonged to spa types t002 or t021, but none among them
      harbored genes coding for PLV. In MLST, most isolates belonged to clones ST5 or
      ST1776. However, we found one subject who carried a novel clone, ST2594. Two out
      of six MRSA carriers had household contacts colonized with isolates similar to
      theirs. Our study pointed to dissemination of community-associated MRSA among the
      Brazilian population. 

PMID- 24663820
TI  - CT halo sign as an imaging marker for response to adoptive cell therapy in
      metastatic melanoma with pulmonary metastases.
AB  - OBJECTIVES: The halo sign refers to a zone of ground-glass attenuation
      surrounding a pulmonary nodule. Pulmonary metastatic nodules exhibiting a halo
      sign are seen mainly in hypervascular tumours. We describe the appearance of a
      halo sign following treatment of adoptive transfer of autologous tumour
      infiltrating lymphocytes (TIL) to melanoma patients with lung metastases.
      METHODS: The study included 29 melanoma patients with pulmonary metastases who
      received TIL therapy. Pre- and post-treatment chest CTs were retrospectively
      reviewed for the presence of a halo sign and its correlation with therapeutic
      response. RESULTS: A pulmonary halo sign was not seen in any pre-treatment CT. It
      was observed in four of 12 patients who responded to the therapy but not in those
      who failed to respond. Significant differences were found between response ratio
      in patients in whom post-TIL halo sign appeared compared with those without the
      halo sign (p = 0.02). CONCLUSIONS: The appearance of a CT halo sign in melanoma
      with lung metastases following TIL therapy may indicate antitumoral effect and a
      good response to therapy. Our findings emphasize the importance of applying new
      assessment criteria for immunological anticancer therapies. KEY POINTS: Tumour
      infiltrating lymphocytes (TIL) in melanoma patients is a promising novel
      immunotherapy. Post-therapy pulmonary halo sign appeared in one-third of TIL
      responders . Pulmonary halo sign may serve as an imaging marker for antitumoral
      activity.

PMID- 24663821
TI  - Diagnostic accuracy of segmental enhancement inversion for diagnosis of renal
      oncocytoma at biphasic contrast enhanced CT: systematic review.
AB  - OBJECTIVES: To use systematic review to evaluate the diagnostic accuracy of
      segmental enhancement inversion (SEI) at contrast-enhanced biphasic multi
      detector computed tomography (MDCT) for the diagnosis of renal oncocytoma.
      METHODS: Several electronic databases were searched through October 2013. Two
      reviewers independently selected studies that met the inclusion criteria and
      extracted data. Study quality was assessed with the QUADAS-2 tool. The primary 2
      * 2 data were investigated with forest plot and ROC plot of sensitivity and
      specificity. RESULTS: Four studies met the inclusion criteria (307 patients).
      Considerable heterogeneity between studies precluded meta-analysis. Two studies
      from the same group of investigators demonstrated reasonable diagnostic accuracy
      (sensitivity 59-80 % and specificity 87-99 %), while two others did not
      (sensitivity 0-6 %, specificity 93-100 %). Possible reasons for this include
      timing of biphasic MDCT and methods of interpretation but not size of lesion.
      CONCLUSIONS: SEI is a specific imaging finding of renal oncocytoma with highly
      variable sensitivity. This substantial heterogeneity across studies and between
      institutions suggests that further validation of this imaging finding is
      necessary prior to application in clinical practice. KEY POINTS: SEI on CT in
      small renal masses is specific for oncocytoma. Sensitivity of SEI varies
      substantially between studies and across institutions. Variability could relate
      to CT timing or methods of interpretation. High accuracy of SEI has only been
      reported by one group. Validation of SEI is needed prior to clinical
      implementation.

PMID- 24663822
TI  - Prediction of presence of kidney disease in a general patient population
      undergoing intravenous iodinated contrast enhanced computed tomography.
AB  - OBJECTIVE: To assess which risk factors can be used to reduce superfluous
      estimated glomerular filtration rate (eGFR) measurements before intravenous
      contrast medium administration. METHODS: In consecutive patients, all decreased
      eGFR risk factors were assessed: diabetes mellitus (DM), history of
      urologic/nephrologic disease (HUND), nephrotoxic medication, cardiovascular
      disease, hypertension, age > 60 years, anaemia, malignancy and multiple
      myeloma/M. Waldenstrom. We studied four models: (1) all risk factors, (2) DM,
      HUND, hypertension, age > 60 years; (3) DM, HUND, cardiovascular disease,
      hypertension; (4) DM, HUND, age > 75 years and congestive heart failure. For each
      model, association with eGFR < 60 ml/min/1.73 m(2) or eGFR < 45 ml/min/1.73 m(2)
      was studied. RESULTS: A total of 998 patients, mean age 59.94 years were
      included; 112 with eGFR < 60 ml/min/1.73 m(2) and 30 with eGFR < 45 ml/min/1.73
      m(2). Model 1 detected 816 patients: 108 with eGFR < 60 ml/min/1.73 m(2) and all
      30 with eGFR < 45 ml/min/1.73 m(2). Model 2 detected 745 patients: 108 with eGFR
      < 60 ml/min/1.73 m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Model 3
      detected 622 patients: 100 with eGFR < 60 ml/min/1.73 m(2) and all 30 with eGFR <
      45 ml/min/1.73 m(2). Model 4 detected 440 patients: 86 with eGFR < 60 ml/min/1.73
      m(2) and all 30 with eGFR < 45 ml/min/1.73 m(2). Associations were significant (p
      < 0.001). CONCLUSION: Model 4 is most effective, resulting in the lowest
      proportion of superfluous eGFR measurements while detecting all patients with
      eGFR < 45 ml/min/1.73 m(2) and most with eGFR < 60 ml/min/1.73 m(2). KEY POINTS:
      A major risk factor for contrast-induced nephropathy (CIN) is kidney disease.
      Risk factors are used to identify patients with pre-existent kidney disease.
      Evidence for risk factors to identify patients with kidney disease is limited.
      The number of eGFR measurements to detect kidney disease can be reduced.

PMID- 24663823
TI  - Multiple primary tumors following stage II and III rectal cancer in patients
      receiving radiotherapy, 1998-2010.
AB  - OBJECTIVE: This report investigated the impact of radiation therapy among stage
      II/III rectal cancer patients who were resected for cure and then developed
      second primary cancer. METHODS: The analysis included patients diagnosed with
      rectal cancer from 1992 to 2010 and who were registered in the National Cancer
      Institute's Surveillance, Epidemiology and End Results database. Standardized
      incidence ratios assessed the location of second primary cancers by the receipt
      and sequence of radiation therapy. A Cox proportional hazards model examined the
      predictors for patients who developed second primary cancers. RESULTS: The hazard
      ratio for developing any type of second primary was 12 % higher in patients
      receiving preoperative radiotherapy, Hazard Ratio and 95 % confidence interval,
      HR 95 % CI 1.12 (1.0, 1.2), and 33 % lower for patients receiving postoperative
      radiotherapy, HR 95 % CI 0.75 (0.7, 0.8), relative to patients who did not
      receive radiation therapy. The location of the second cancer varied by both the
      receipt and sequence of radiation therapy. Secondary rectal cancers were reduced
      170 % after postoperative radiation and 103 % after preoperative radiation,
      compared to the non-receipt of radiation therapy. The impact of radiation therapy
      on secondary colon cancers was not as marked. Rectal cancer patients undergoing
      radiation therapy are at a higher risk of thyroid cancers and leukemia, but males
      have a lower risk of prostate cancer. CONCLUSIONS: While preoperative radiation
      therapy is advantageous for reducing rectal cancer recurrence, this study
      identifies advantages of postoperative radiation for reducing second primary
      cancers. This research will help improve recommendations for postdiagnosis
      surveillance in patients with rectal cancer.

PMID- 24663825
TI  - 120mJ Q-switched Er:YAG laser at 1645nm.
AB  - A fibre-coupled 1.47um laser diode end-pumped Er:YAG laser system comprising one
      oscillator and two single pass amplifiers is described. 120mJ pulses at a 30Hz
      repetition rate and 1.64um emission wavelength are reported. 

PMID- 24663824
TI  - Involvement of CD74 in head and neck squamous cell carcinomas.
AB  - PURPOSE: While macrophage migration inhibitory factor (MIF) has been extensively
      studied in the context of inflammation and inflammatory disorders, less work has
      been devoted to its involvement in cancer, notably in neoplastic progression. In
      a previous study, we have found evidence that MIF plays a role in head and neck
      squamous cell carcinomas (HNSCC). The current investigations were undertaken in
      order to estimate the importance of the MIF receptor, CD74 in the progression of
      HNSCC. METHODS AND RESULTS: In a cohort of 46 cases of oral cavity carcinomas,
      immunohistochemical staining revealed an increase in CD74 expression during
      progression from benign lesions to carcinoma. As shown by cell culture
      experiments using squamous carcinoma cell line (SCCVII) transduced with anti-CD74
      shRNA, the amount of cell-produced VEGF was lower in SCCVII CD74KD cell line
      compared with control SCCVII CD74sc cell line, suggesting that CD74 could be
      implicated in angiogenesis in vivo. Furthermore, knockdown of CD74 decreased
      proliferation of SCCVII cells in vitro. The migration of SCCVII cells, as well as
      the cell secretion of matrix metallopeptidase 9, was also negatively affected by
      CD74 knockdown. These observations in vitro were confirmed in an orthotopic mouse
      model of SCC where tumors produced by SCCVII CD74KD cell inoculation were found
      to grow more slowly than tumors generated by SCCVII CD74sc cells. CONCLUSION: The
      clinical observations and experimental data reported here suggest that CD74, as
      well as MIF, plays a pivotal role in HNSCC progression.

PMID- 24663826
TI  - Amplitude-phase coupling and chirp in quantum-dot lasers: influence of charge
      carrier scattering dynamics.
AB  - We investigate the dependence of the amplitude-phase coupling in quantum-dot (QD)
      lasers on the charge-carrier scattering timescales. The carrier scattering
      processes influence the relaxation oscillation parameters, as well as the
      frequency chirp, which are both important parameters when determining the
      modulation performance of the laser device and its reaction to optical
      perturbations. We find that the FM/AM response exhibits a strong dependence on
      the modulation frequency, which leads to a modified optical response of QD lasers
      when compared to conventional laser devices. Furthermore, the frequency response
      curve changes with the scattering time scales, which can allow for an
      optimization of the laser stability towards optical perturbations. 

PMID- 24663827
TI  - Investigation of elliptically polarized injection locked states in VCSELs subject
      to orthogonal optical injection.
AB  - We demonstrate experimentally the existence of the elliptically polarized
      injection-locked (EPIL) state. This state is observed when a single-transverse
      mode VCSEL is subject to orthogonal optical injection. The spectral feature of
      the EPIL state is verified and the power of each polarization is measured. The
      regime of the EPIL state is identified in the parameter plane of frequency
      detuning and injection power for different bias currents. As current decreases
      the frequency detuning range for the EPIL to exist is narrower and shifts toward
      the negative frequency detuning. Periodic dynamics of the VCSEL is found in the
      neighborhood of the EPIL regime. 

PMID- 24663828
TI  - Coherent perfect absorption, transmission, and synthesis in a double-cavity
      optomechanical system.
AB  - We study a double-cavity optomechanical system in which a movable mirror with
      perfect reflection is inserted between two fixed mirrors with partial
      transmission. This optomechanical system is driven from both fixed end mirrors in
      a symmetric scheme by two strong coupling fields and two weak probe fields. We
      find that three interesting phenomena: coherent perfect absorption (CPA),
      coherent perfect transmission (CPT), and coherent perfect synthesis (CPS) can be
      attained within different parameter regimes. That is, we can make two input probe
      fields totally absorbed by the movable mirror without yielding any energy output
      from either end mirror (CPA); make an input probe field transmitted from one end
      mirror to the other end mirror without suffering any energy loss in the two
      cavities (CPT); make two input probe fields synthesized into one output probe
      field after undergoing either a perfect transmission or a perfect reflection
      (CPS). These interesting phenomena originate from the efficient hybrid coupling
      of optical and mechanical modes and may be all-optically controlled to realize
      novel photonic devices in quantum information networks. 

PMID- 24663829
TI  - Fiber-distributed Ultra-wideband noise radar with steerable power spectrum and
      colorless base station.
AB  - A fiber-distributed Ultra-wideband (UWB) noise radar was achieved, which consists
      of a chaotic UWB noise source based on optoelectronic oscillator (OEO), a fiber
      distributed transmission link, a colorless base station (BS), and a cross
      correlation processing module. Due to a polarization modulation based microwave
      photonic filter and an electrical UWB pass-band filter embedded in the feedback
      loop of the OEO, the power spectrum of chaotic UWB signal could be shaped and
      notch-filtered to avoid the spectrum-overlay-induced interference to the narrow
      band signals. Meanwhile, the wavelength-reusing could be implemented in the BS by
      means of the distributed polarization modulation-to-intensity modulation
      conversion. The experimental comparison for range finding was carried out as the
      chaotic UWB signal was notch-filtered at 5.2 GHz and 7.8 GHz or not. Measured
      results indicate that space resolution with cm-level could be realized after 3-km
      fiber transmission thanks to the excellent self-correlation property of the UWB
      noise signal provided by the OEO. The performance deterioration of the radar
      raised by the energy loss of the notch-filtered noise signal was negligible. 

PMID- 24663830
TI  - Optically compensated polarization reciprocity in interferometric fiber-optic
      gyroscopes.
AB  - Polarization reciprocity is studied both theoretically and experimentally in an
      optically compensated configuration of interferometric fiber optic gyroscope
      (IFOG). In conventional IFOGs based on the minimal scheme, the output port of the
      coil coupler cannot be used mainly because of its polarization nonreciprocity
      (PN), and thus it is usually called the "nonreciprocal port". We show that the PN
      errors at the nonreciprocal port are effectively eliminated by optical
      compensation. With this unique property, the optically compensated IFOG can
      possess two low-PN ports for rotation sensing at the same time. From another
      perspective, one port IFOGs are possible to be constructed with less structural
      complexity. 

PMID- 24663831
TI  - Optimal estimation in polarimetric imaging in the presence of correlated noise
      fluctuations.
AB  - We quantitatively analyze how a polarization-sensitive imager can overcome the
      precision of a standard intensity camera when estimating a parameter on a
      polarized source over an intense background. We show that the gain is maximized
      when the two polarimetric channels are perturbed with significantly correlated
      noise fluctuations. An optimal estimator is derived and compared to standard
      intensity and polarimetric estimators. 

PMID- 24663832
TI  - Double color image encryption using iterative phase retrieval algorithm in
      quaternion gyrator domain.
AB  - This paper describes a novel algorithm to encrypt double color images into a
      single undistinguishable image in quaternion gyrator domain. By using an
      iterative phase retrieval algorithm, the phase masks used for encryption are
      obtained. Subsequently, the encrypted image is generated via cascaded quaternion
      gyrator transforms with different rotation angles. The parameters in quaternion
      gyrator transforms and phases serve as encryption keys. By knowing these keys,
      the original color images can be fully restituted. Numerical simulations have
      demonstrated the validity of the proposed encryption system as well as its
      robustness against loss of data and additive Gaussian noise. 

PMID- 24663833
TI  - Single CuTCNQ charge transfer complex nanowire as ultra high responsivity photo
      detector.
AB  - We report ultra large photo responsivity R (ratio of photo-generated current to
      absorbed power) in a single nanowire (NW) device made from a single strand of a
      nanowire (diameter ~30nm and length ~200nm) of an organomettalic semiconducting
      charge transfer complex material of CuTCNQ. The device shows responsivity of
      8x10(4) A/Watt at 1 volt applied bias with an enhancement over the dark current
      exceeding 10(5) at zero bias. The observed photo current has a spectral
      dependence that strongly follows the main absorption peak (close to 405 nm)
      showing the primary role of absorbed photo-generated carriers.

PMID- 24663834
TI  - Engineering the mode parity of the ground state in photonic crystal molecules.
AB  - We propose a way to engineer the design of photonic molecules, realized by
      coupling two photonic crystal cavities, that allows an accurate control of the
      parity of their ground states. The spatial distribution of the fundamental mode
      of photonic molecules can be tuned from a bonding to an antibonding character by
      a local and continuous modification of the dielectric environment in between the
      two coupled cavities. In the systems that we investigate the transition could be
      experimentally accomplished by post-fabrication methods in either a reversible or
      an irreversible way. We notably find that the mode parity exchange is tightly
      related to a dramatic variation of the far field emission pattern, leading to the
      possibility to exploit these systems and techniques for future applications in
      optoelectronics. 

PMID- 24663835
TI  - Embedded pupil function recovery for Fourier ptychographic microscopy.
AB  - We develop and test a pupil function determination algorithm, termed embedded
      pupil function recovery (EPRY), which can be incorporated into the Fourier
      ptychographic microscopy (FPM) algorithm and recover both the Fourier spectrum of
      sample and the pupil function of imaging system simultaneously. This EPRY-FPM
      algorithm eliminates the requirement of the previous FPM algorithm for a priori
      knowledge of the aberration in the imaging system to reconstruct a high quality
      image. We experimentally demonstrate the effectiveness of this algorithm by
      reconstructing high resolution, large field-of-view images of biological samples.
      We also illustrate that the pupil function we retrieve can be used to study the
      spatially varying aberration of a large field-of-view imaging system. We believe
      that this algorithm adds more flexibility to FPM and can be a powerful tool for
      the characterization of an imaging system's aberration. 

PMID- 24663836
TI  - Chalcogenide phase-change thin films used as grayscale photolithography
      materials.
AB  - Chalcogenide phase-change thin films are used in many fields, such as optical
      information storage and solid-state memory. In this work, we present another
      application of chalcogenide phase-change thin films, i.e., as grayscale
      photolithgraphy materials. The grayscale patterns can be directly inscribed on
      the chalcogenide phase-change thin films by a single process through direct laser
      writing method. In grayscale photolithography, the laser pulse can induce the
      formation of bump structure, and the bump height and size can be precisely
      controlled by changing laser energy. Bumps with different height and size present
      different optical reflection and transmission spectra, leading to the different
      gray levels. For example, the continuous-tone grayscale images of lifelike bird
      and cat are successfully inscribed onto Sb(2)Te(3) chalcogenide phase-change thin
      films using a home-built laser direct writer, where the expression and appearance
      of the lifelike bird and cat are fully presented. This work provides a way to
      fabricate complicated grayscale patterns using laser-induced bump structures onto
      chalcogenide phase-change thin films, different from current techniques such as
      photolithography, electron beam lithography, and focused ion beam lithography.
      The ability to form grayscale patterns of chalcogenide phase-change thin films
      reveals many potential applications in high-resolution optical images for
      micro/nano image storage, microartworks, and grayscale photomasks.

PMID- 24663837
TI  - RGB-NIR multispectral camera.
AB  - A multispectral imaging technique with a new CMOS camera is proposed. With a four
      channel Bayer patterns, the camera can acquire four spectral images
      simultaneously. We have developed a color correction process to obtain accurate
      color information, and we have also demonstrated its applications on portrait
      enhancement, shadow removal, and vein enhancement. 

PMID- 24663839
TI  - Jumping phase control in interband photonic transition.
AB  - Indirect interband photonic transition provides a nonmagnetic and linear scheme
      to achieve optical isolation in integrated photonics. In this paper, we
      demonstrate that the nonreciprocal transition can be induced through two pathways
      respectively by different modulation designs. At the end of those pathways, the
      two final modes have pi phaseshift. We call this phenomenon jumping phase control
      since this approach provides a method to control the mode phase after the
      conversion. This approach also yields a novel way to generate nonreciprocal
      phaseshift and may contribute to chip-scale optoelectronic applications. 

PMID- 24663838
TI  - Common path in-line holography using enhanced joint object reference digital
      interferometers.
AB  - Joint object reference digital interferometer (JORDI) is a recently developed
      system capable of recording holograms of various types [Opt. Lett. 38(22), 4719
      (2013)]. Presented here is a new enhanced system design that is based on the
      previous JORDI. While the previous JORDI has been based purely on diffractive
      optical elements, displayed on spatial light modulators, the present design
      incorporates an additional refractive objective lens, thus enabling hologram
      recording with improved resolution and increased system applicability.
      Experimental results demonstrate successful hologram recording for various types
      of objects, including transmissive, reflective, three-dimensional, phase and
      highly scattering objects. The resolution limit of the system is analyzed and
      experimentally validated. Finally, the suitability of JORDI for microscopic
      applications is verified as a microscope objective based configuration of the
      system is demonstrated. 

PMID- 24663840
TI  - Holographic kinetics for mixed volume gratings in gold nanoparticles doped
      photopolymer.
AB  - A holographic kinetic model is proposed to quantitatively represent the dynamics
      of mixed volume gratings in a bulk gold nanoparticles (NPs) doped photopolymer.
      Due to the polymerization-driven multicomponent diffusion, the volume refractive
      index grating is induced by the periodic spatial distribution of photoproduct
      while the absorption grating is formed by the periodic spatial distribution of
      gold NPs. By simulating this model with the characterization of time varying
      absorption modulation, it is capable to describe the behavior of gold NPs in both
      the polymerization and the multicomponent diffusion process. The temporal
      evolution of refractive index modulation and absorption modulation can be
      extracted, respectively, from a diffraction efficiency curve by fitting the
      model. The established model could be an effective method for understanding the
      photophysical and photochemical mechanism of holographic nanocomposite. 

PMID- 24663841
TI  - Phase regeneration of DPSK signals in a silicon waveguide with reverse-biased p-i
      n junction.
AB  - Phase regeneration of differential phase-shift keying (DPSK) signals is
      demonstrated using a silicon waveguide as nonlinear medium for the first time. A
      p-i-n junction across the waveguide enables decreasing the nonlinear losses
      introduced by free-carrier absorption (FCA), thus allowing phase-sensitive
      extinction ratios as high as 20 dB to be reached under continuous-wave (CW)
      pumping operation. Furthermore the regeneration properties are investigated under
      dynamic operation for a 10-Gb/s DPSK signal degraded by phase noise, showing
      receiver sensitivity improvements above 14 dB. Different phase noise frequencies
      and amplitudes are examined, resulting in an improvement of the performance of
      the regenerated signal in all the considered cases. 

PMID- 24663842
TI  - Refractive index sensing characterization of a singlemode-claddingless-singlemode
      fiber structure based fiber ring cavity laser.
AB  - This paper firstly demonstrated the refractive index (RI) characteristics of a
      singlemode-claddingless-singlemode fiber structure filter based fiber ring cavity
      laser sensing system. The experiment shows that the lasing wavelength shifts to
      red side with the ambient RI increase. Linear and parabolic fitting are both done
      to the measurements. The linear fitting result shows a good linearity for
      applications in some areas with the determination coefficient of 0.993. And a
      sensitivity of ~131.64nm/RIU is experimentally achieved with the aqueous solution
      RI ranging from 1.333 to 1.3707, which is competitively compared to other
      existing fiber-optic sensors. While the 2 order polynomial fitting function,
      which determination relationship is higher than 0.999, can be used to some more
      rigorous monitoring. The proposed fiber laser has a SNR of ~50dB, and 3dB
      bandwidth ~0.03nm. 

PMID- 24663843
TI  - Achromatic Savart polariscope: choice of materials.
AB  - This paper presents the achromatization of Savart Polariscope to decrease the
      lateral-shear dispersion in the lateral displacement. The achromatic Savart
      Polariscope can be made from two different birefringent crystal materials. The
      achromatic model for the choices of material is presented. The achievements and
      performances of different achromatic Savart Polariscopes are demonstrated with
      numerical simulations and ray tracing program. The chromatic variation in lateral
      displacement can be reduced by an order of magnitude across the spectral range
      0.4MUm to 0.9MUm. 

PMID- 24663844
TI  - High responsivity, low dark current, heterogeneously integrated thin film Si
      photodetectors on rigid and flexible substrates.
AB  - We report thin film single crystal silicon photodetectors (PDs), composed of 13-
      25 MUm thick silicon, heterogeneously bonded to transparent Pyrex(r) and flexible
      Kapton(r) substrates. The measured responsivity and dark current density of the
      PDs on pyrex is 0.19 A/W - 0.34 A/W (lambda = 470 nm - 600 nm) and 0.63 nA/cm(2),
      respectively, at ~0V bias. The measured responsivity and dark current density of
      the flexible PDs is 0.16 A/W - 0.26 A/W (lambda = 470 nm - 600 nm) and 0.42
      nA/cm(2), respectively, at a ~0V bias. The resulting responsivity-to-dark current
      density ratios for the reported rigid and flexible PDs are 0.3-0.54 cm(2)/nW and
      0.38-0.62 cm(2)/nW, respectively. These are the highest reported responsivity-to
      dark current density ratios for heterogeneously bonded thin film single crystal
      Si PDs, to the best of our knowledge. These PDs are customized for applications
      in biomedical imaging and integrated biochemical sensing.

PMID- 24663845
TI  - Fast conversion of digital Fresnel hologram to phase-only hologram based on
      localized error diffusion and redistribution.
AB  - Past research has demonstrated that a digital, complex Fresnel hologram can be
      converted into a phase-only hologram with the use of the bi-direction error
      diffusion (BERD) algorithm. However, the recursive nature error diffusion process
      is lengthy and increases monotonically with hologram size. In this paper, we
      propose a method to overcome this problem. Briefly, each row of a hologram is
      partitioned into short non-overlapping segments, and a localized error diffusion
      algorithm is applied to convert the pixels in each segment into phase only
      values. Subsequently, the error signal is redistributed with low-pass filtering.
      As the operation on each segment is independent of others, the conversion process
      can be conducted at high speed with the graphic processing unit. The hologram
      obtained with the proposed method, known as the Localized Error Diffusion and
      Redistribution (LERDR) hologram, is over two orders of magnitude faster than that
      obtained by BERD for a 2048*2048 hologram, exceeding the capability of generating
      quality phase-only holograms in video rate. 

PMID- 24663846
TI  - Pump-linewidth-tolerant optical wavelength conversion for high-order QAM signals
      using coherent pumps.
AB  - Optical wavelength conversion (OWC) is expected to be a desirable function in
      future optical transparent networks. Since high-order quadrature amplitude
      modulation (QAM) is more sensitive to the phase noise, in the OWC of high-order
      QAM signals, it is crucial to suppress the extra noise introduced in the OWC
      subsystem, especially for the scenario with multiple cascaded OWCs. Here, we
      propose and experimentally demonstrate a pump-linewidth-tolerant OWC scheme
      suitable for high-order QAM signals using coherent two-tone pumps. Using 3.5-MHz
      linewidth distributed feedback (DFB) lasers as pump sources, our scheme enables
      wavelength conversion of both 16QAM and 64QAM signals with negligible power
      penalty, in a periodically-poled Lithium Niobate (PPLN) waveguide based OWC. We
      also demonstrate the performance of pump phase noise cancellation, showing that
      such coherent two-tone pump schemes can eliminate the need for ultra-narrow
      linewidth pump lasers and enable practical implementation of low-cost OWC in
      future dynamic optical networks. 

PMID- 24663847
TI  - Generation of silver nanoparticles with controlled size and spatial distribution
      by pulsed laser irradiation of silver ion-doped glass.
AB  - Silver ions were driven into glass by a direct current electric field-assisted
      ion exchange technique. The silver ion exchanged glass was then irradiated by
      laser pulses of 10 ns and 10 ps in length at 355 nm for comparison purposes. In
      both cases, laser irradiation led to the formation of a metallic-like film at the
      surface of the ion exchange glass. Scanning electron microscopy showed that the
      films consist of a very dense single layer of silver nanoparticles with similar
      particle sizes and separation. Irradiation with different laser parameters shows
      no significant difference in transmission spectra and modification width between
      ps- and ns-pulsed lasers. Particle sizes and separation at the surface are
      increasing with increasing laser power, and are larger for picosecond pulsed
      laser irradiation. It is also shown that the film formation is a thermal process.

PMID- 24663848
TI  - The impact of emission mechanisms on the long-lived states around avoided
      resonance crossings in chaotic microcavity.
AB  - Here we demonstrate the impacts of emission mechanisms on the light confinements
      in open systems. Taking the oval-shaped cavities as examples, we show that the
      enhancements in quality (Q) factors are usually associated with the universal
      emissions. When the coupled resonances have similar far field patterns, the Q
      factor of the long-lived resonance has the possibility to be enhanced by the
      coherent destruction at the decay channels. Otherwise, the Q factors of long
      lived resonances are usually reduced around the level crossings. 

PMID- 24663849
TI  - 3D surface mapping of freeform optics using wavelength scanning lateral shearing
      interferometry.
AB  - Freeform optics have emerged as promising components in diverse applications due
      to the potential for superior optical performance. There are many research fields
      in the area ranging from fabrication to measurement, with metrology being one of
      the most challenging tasks. In this paper, we describe a new variant of lateral
      shearing interferometer with a tunable laser source that enables 3D surface
      profile measurements of freeform optics with high speed, high vertical
      resolution, large departure, and large field-of-view. We have verified the
      proposed technique by comparing our measurement result with that of an existing
      technique and measuring a representative freeform optic. 

PMID- 24663850
TI  - Estimating FPAR of maize canopy using airborne discrete-return LiDAR data.
AB  - The fraction of absorbed photosynthetically active radiation (FPAR) is a key
      parameter for ecosystem modeling, crop growth monitoring and yield prediction.
      Ground-based FPAR measurements are time consuming and labor intensive. Remote
      sensing provides an alternative method to obtain repeated, rapid and inexpensive
      estimates of FPAR over large areas. LiDAR is an active remote sensing technology
      and can be used to extract accurate canopy structure parameters. A method to
      estimating FPAR of maize from airborne discrete-return LiDAR data was developed
      and tested in this study. The raw LiDAR point clouds were processed to separate
      ground returns from vegetation returns using a filter method over a maize field
      in the Heihe River Basin, northwest China. The fractional cover (fCover) of maize
      canopy was computed using the ratio of canopy return counts or intensity sums to
      the total of returns or intensities. FPAR estimation models were established
      based on linear regression analysis between the LiDAR-derived fCover and the
      field-measured FPAR (R(2) = 0.90, RMSE = 0.032, p < 0.001). The reliability of
      the constructed regression model was assessed using the leave-one-out cross
      validation procedure and results show that the regression model is not
      overfitting the data and has a good generalization capability. Finally, 15
      independent field-measured FPARs were used to evaluate accuracy of the LiDAR
      predicted FPARs and results show that the LiDAR-predicted FPAR has a high
      accuracy (R(2) = 0.89, RMSE = 0.034). In summary, this study suggests that the
      airborne discrete-return LiDAR data could be adopted to accurately estimate FPAR
      of maize.

PMID- 24663851
TI  - Kerr-lens mode-locked femtosecond polycrystalline Cr2+:ZnS and Cr2+:ZnSe lasers.
AB  - We report the first Kerr-lens mode-locked polycrystalline Cr(2+):ZnS and
      Cr(2+):ZnSe lasers, with pulse duration of 125 fs at a pulse repetition rate of
      160 MHz, emitting around 2.3 - 2.4 um. The mode-locked lasers were pumped by a
      radiation of 1550 nm Er-fiber amplifier seeded by semiconductor laser. The long
      term stable Kerr-lens mode-locked laser operation with the output power of 30 mW
      (Cr(2+):ZnS) and 60 mW (Cr(2+):ZnSe) was obtained. We also demonstrate
      amplification of the fs laser pulse train in a cw pumped single-pass
      polycrystalline Cr(2+):ZnS laser amplifier.

PMID- 24663852
TI  - Influence of localized surface plasmon resonance and free electrons on the
      optical properties of ultrathin Au films: a study of the aggregation effect.
AB  - The contributions of localized surface plasmon resonance (LSPR) and Drude (free
      electrons) absorption to the complex dielectric function of ultrathin Au films
      were investigated with spectroscopic ellipsometry. When the Au film thickness is
      thinner than ~10 nm, Au nanoparticles (NPs) are formed as a result of the
      discontinuity in the films, leading to the emergence of LSPR of Au NPs; and the
      LSPR exhibits a splitting when the films thinner than ~8 nm, which could be
      attributed to the near-field coupling of the Au NPs and/or the inhomogeneous
      polarizations of the Au NPs. On the other hand, the delocalization of electrons
      in Au NPs due to the aggregation of Au NPs in a thicker film leads to an increase
      in the free-electron absorption and a suppression of the LSPR. 

PMID- 24663853
TI  - Effects of spatial coherence in diffraction phase microscopy.
AB  - Quantitative phase imaging systems using white light illumination can exhibit
      lower noise figures than laser-based systems. However, they can also suffer from
      object-dependent artifacts, such as halos, which prevent accurate reconstruction
      of the surface topography. In this work, we show that white light diffraction
      phase microscopy using a standard halogen lamp can produce accurate height maps
      of even the most challenging structures provided that there is proper spatial
      filtering at: 1) the condenser to ensure adequate spatial coherence and 2) the
      output Fourier plane to produce a uniform reference beam. We explain that these
      object-dependent artifacts are a high-pass filtering phenomenon, establish design
      guidelines to reduce the artifacts, and then apply these guidelines to eliminate
      the halo effect. Since a spatially incoherent source requires significant spatial
      filtering, the irradiance is lower and proportionally longer exposure times are
      needed. To circumvent this tradeoff, we demonstrate that a supercontinuum laser,
      due to its high radiance, can provide accurate measurements with reduced exposure
      times, allowing for fast dynamic measurements. 

PMID- 24663854
TI  - Phase retrieval approach based on the normalized difference maps induced by three
      interferograms with unknown phase shifts.
AB  - From three interferograms with unknown phase shifts, an innovative phase
      retrieval approach based on the normalized difference maps is proposed. Using the
      subtraction operation between interferograms, two difference maps without
      background can be achieved. To eliminate the amplitude inequality of difference
      maps, normalization process is employed so that two normalized difference maps
      are obtained. Finally, combining two normalized difference maps and two-step
      phase retrieval algorithm, the measured phase with high precision can be
      retrieved rapidly. Comparing with the conventional two-step phase retrieval
      algorithm with high-pass filtering, the accuracy and processing time of the
      proposed approach are greatly improved. Importantly, when the phase shift is
      close to pi, almost all two-step algorithms become invalid, but the proposed
      approach still performs well. That is, the proposed normalized difference maps
      approach is suitable for the phase retrieval with arbitrary phase shifts. 

PMID- 24663855
TI  - Size dependence of band-gaps in a one-dimensional plasmonic crystal.
AB  - The dependence of the plasmonic band gap on size of a one-dimensional plasmonic
      crystal with a rectangular cross-section has been investigated by
      cathodoluminescence, using a 200-keV scanning transmission electron microscope.
      The band edge character at points Gamma and X changes in correlation with the
      corresponding Fourier component of the surface shape. The calculation by the
      rigorous coupled-wave analysis (RCWA) method reproduces well the observed size
      dependence of the band edge energies on terrace width and height, though some
      deviation in magnitude remains. The beam-scan spectral images clearly reveal
      symmetric and anti-symmetric characters of the standing waves of the band edge
      modes. The two modes at the band edges are different in the surface plasmon
      Polariton (SPP)-light conversion efficiency and exchange their energy positions
      by changing terrace width. 

PMID- 24663856
TI  - Application of clustering global optimization to thin film design problems.
AB  - Refinement techniques usually calculate an optimized local solution, which is
      strongly dependent on the initial formula used for the thin film design. In the
      present study, a clustering global optimization method is used which can
      iteratively change this initial formula, thereby progressing further than in the
      case of local optimization techniques. A wide panel of local solutions is found
      using this procedure, resulting in a large range of optical thicknesses. The
      efficiency of this technique is illustrated by two thin film design problems, in
      particular an infrared antireflection coating, and a solar-selective absorber
      coating. 

PMID- 24663857
TI  - Laser emission from diode-pumped Nd:YAG ceramic waveguide lasers realized by
      direct femtosecond-laser writing technique.
AB  - We report on realization of buried waveguides in Nd:YAG ceramic media by direct
      femtosecond-laser writing technique and investigate the waveguides laser emission
      characteristics under the pump with fiber-coupled diode lasers. Laser pulses at
      1.06 MUm with energy of 2.8 mJ for the pump with pulses of 13.1-mJ energy and
      continuous-wave output power of 0.49 W with overall optical efficiency of 0.13
      were obtained from a 100-MUm diameter circular cladding waveguide realized in a
      0.7-at.% Nd:YAG ceramic. A circular waveguide of 50-MUm diameter yielded laser
      pulses at 1.3 MUm with 1.2-mJ energy. 

PMID- 24663858
TI  - Anti-glare LED lamps with adjustable illumination light field.
AB  - We introduce a type of LED light-gauge steel frame lamp with an adjustable
      illumination light field that does not require a diffusion plate. Base on the
      Monte Carlo ray tracing method, this lamp has a good glare rating (GR) of 17.5 at
      3050 lm. Compared with the traditional LED light-gauge steel frame lamp (without
      diffusion plate), the new type has low GR. The adjustability of the illumination
      light field could improve the zebra effect caused by the inadequate illumination
      light field of the lamp. Meanwhile, we adopt the retinal image analysis to
      discuss the influence of GR on vision. High GR could reflect stray light on the
      retinal image, which will reduce vision clarity and hasten the feeling of eye
      fatigue. 

PMID- 24663859
TI  - Design and characterization of whispering-gallery spiral waveguides.
AB  - Whispering gallery delay lines have demonstrated record propagation length on a
      silicon chip and can provide a way to transfer certain applications of optical
      fiber to wafer-based systems. Their design and fabrication requires careful
      control of waveguide curvature and etching conditions to minimize connection
      losses between elements of the delay line. Moreover, loss characterization based
      on optical backscatter requires normalization to account for the impact of
      curvature on backscatter rate. In this paper we provide details on design of
      Archimedean whispering-gallery spiral waveguides, their coupling into cascaded
      structures, as well as optical loss characterization by optical backscatter
      reflectometry. 

PMID- 24663860
TI  - Parasitic-light-suppressed quasi-phase-matched optical parametric oscillation
      device.
AB  - Nonlinear absorption - such as green-induced infrared absorption (GRIIRA) -
      increases the risk of the catastrophic damage during high peak- power wavelength
      conversion. We propose a novel concept to suppress parasitic green second
      harmonic generation (SHG) in optical parametric oscillation (OPO) using specially
      engineered quasi-phase-matched (QPM) structures. This selective suppression was
      achieved by relative pi-phase shift in only SHG not OPO. Compared with a periodic
      device, a parasitic-light-suppressed (PLS) QPM device produced smaller normalized
      conversion efficiency in green and maintained singly resonant OPO performance. 

PMID- 24663861
TI  - Tomographic reconstruction of the refractive index with hard X-rays: an efficient
      method based on the gradient vector-field approach.
AB  - The refractive-index gradient vector field approach establishes a connection
      between a tomographic data set of differential phase contrast images and the
      distribution of the partial spatial derivatives of the refractive index in an
      object. The reconstruction of the refractive index in a plane requires the
      integration of its gradient field. This work shows how this integration can be
      efficiently performed by converting the problem to the Poisson equation, which
      can be accurately solved even in the case of noisy and large datasets. The
      performance of the suggested method is discussed and demonstrated experimentally
      by computing the refractive index distribution in both a simple plastic phantom
      and a complex biological sample. The quality of the reconstruction is evaluated
      through the direct comparison with other commonly used methods. To this end, the
      refractive index is retrieved from the same data set using also (1) the filtered
      backprojection algorithm for gradient projections, and (2) the regularized phase
      retrieval procedure. Results show that the gradient vector field approach
      combined with the developed integration technique provides a very accurate
      depiction of the sample internal structure. Contrary to the two other techniques,
      the considered method does not require a preliminary phase-retrieval and can be
      implemented with any advanced computer tomography algorithm. In this work,
      analyzer-based phase contrast images are used for demonstration. Results,
      however, are generally valid and can be applied for processing differential phase
      contrast tomographic data sets obtained with other phase-contrast imaging
      techniques. 

PMID- 24663862
TI  - Nanoscope based on nanowaveguides.
AB  - The far field spatial resolution of conventional optical lenses is of the order
      of the wavelength of light, due to loss in the far field of evanescent, near
      electromagnetic field components. We show that subwavelength details can be
      restored in the far field with an array of divergent nanowaveguides, which map
      the discretized, subwavelength image of an object into a magnified image
      observable with a conventional optical microscope. We demonstrate in simulations
      that metallic nanowires, nanocoaxes, and nanogrooves can be used as such
      nanowaveguides. Thus, an optical microscope capable of subwavelength resolution -
      a nanoscope - can be produced, with possible applications in a variety of fields
      where nanoscale optical imaging is of value. 

PMID- 24663863
TI  - Pulse characterization by THG d-scan in absorbing nonlinear media.
AB  - We report on few-cycle pulse characterization based on third harmonic generation
      dispersion scan (THG d-scan) measurements using thin films of different TiO(2)
      SiO(2) compositions as nonlinear media. By changing the TiO(2) concentration in
      the thin film the band gap and therefore the position of the absorption edge were
      varied. The retrieved pulse durations from different nonlinear media agree within
      5%, and the reconstructed pulse shapes prove to be immune against the absorption
      edges as well. The reason is the robust retrieval algorithm which takes the
      influence of wavelength dependent nonlinearity into account by a spectral weight
      function.

PMID- 24663864
TI  - Enhanced secure strategy for electro-optic chaotic systems with delayed dynamics
      by using fractional Fourier transformation.
AB  - We propose a scheme whereby a time domain fractional Fourier transform (FRFT) is
      used to post process the optical chaotic carrier generated by an electro-optic
      oscillator. The time delay signature of the delay dynamics is successfully masked
      by the FRFT when some conditions are satisfied. Meanwhile the dimension space of
      the physical parameters is increased. Pseudo random binary sequence (PRBS) with
      low bit rate (hundreds of Mbps) is introduced to control the parameters of the
      FRFT. The chaotic optical carrier, FRFT parameters and the PRBS are covered by
      each other so that the eavesdropper has to search the whole key space to crack
      the system. The scheme allows enhancing the security of communication systems
      based on delay dynamics without modifying the chaotic source. In this way, the
      design of chaos based communication systems can be implemented in a modular
      manner. 

PMID- 24663865
TI  - Electro-optic light modulation and THz generation in locally plasma-activated
      silicon nanophotonic devices.
AB  - Silicon is not an electro-optic material by itself but the required second-order
      optical nonlinearity can be induced by breaking the inversion symmetry of the
      crystal lattice. Recently, an attractive approach has been demonstrated based on
      a surface-activation in a CMOS-compatible HBr dry etching process. In this work,
      we further investigate and quantify the second-order nonlinearity induced by this
      process. Using THz near-field probing we demonstrate that this simple and
      versatile process can be applied to locally equip silicon nanophotonic chips with
      micro-scale areas of electro-optic activity. The realization of a first fully
      integrated Mach-Zehnder modulator device - based on this process - is applied to
      quantify the nonlinearity to an effective chi((2)) of 9 +/- 1 pm/V. Analysis of
      the thermal stability of the induced nonlinearity reveals post-processing
      limitations and paths for further efficiency improvements.

PMID- 24663866
TI  - Dispersion tuning with a varifocal diffractive-refractive hybrid lens.
AB  - We present a hybrid diffractive-refractive optical lens doublet consisting of a
      varifocal Moire Fresnel lens and a polymer lens of tunable refractive power. The
      wide range of focal tunability of each lens and the opposite dispersive
      characteristics of the diffractive and the refractive element are exploited to
      obtain an optical system where both the Abbe number and the refractive power can
      be changed separately. We investigate the performance of the proposed hybrid lens
      at zero overall refractive power by tuning the Abbe number of a complementary
      standard lens while maintaining a constant overall focal length for the central
      wavelength. As an application example, the hybrid lens is used to tune to an
      optimal operating regime for quantitative phase microscopy based on a two-color
      transport of intensity (TIE) approach which utilizes chromatic aberrations rather
      than intensity recordings at several planes to reconstruct the optical path
      length of a phase object. 

PMID- 24663867
TI  - Bragg grating writing in PMMA microstructured polymer optical fibers in less than
      7 minutes.
AB  - We demonstrate fiber Bragg grating (FBG) writing in PMMA microstructured Polymer
      Optical Fibers (mPOFs) using UV Phase Mask technique with writing times shorter
      than 10 min. The shortest writing time was 6 minutes and 50 seconds and the
      longest writing time was 8 min and 50 sec. The FBGs were written in a 125 um PMMA
      mPOF having 3-rings of holes, the reflection peaks were centred at 632.6 nm and
      have a reflectivity as high as 26 dB. We also demonstrate how the writing
      dynamics depends on the intensity of the writing beam. 

PMID- 24663868
TI  - Polarization-resolved evanescent wave scattering from gold-coated tilted fiber
      gratings.
AB  - The scatterings of TE- and TM-polarized evanescent wave on the surface of a
      tilted fiber Bragg grating (TFBG) with a 50 nm thick gold coating were
      investigated experimentally by observing radiation patterns from discontinuities
      in the coating. The scattering intensity for TM-polarized light is larger than
      for TE light when the evanescent wave propagates from the coating towards the
      discontinuity. The opposite occurs for light propagating from an uncoated section
      towards the coating edge. However in the latter case the scattering is much
      weaker. These results confirm that cladding modes with TE and TM polarization can
      be excited selectively with a TFBG, and that they scatter light differentially at
      discontinuities. These results are used to propose a simple polarimeter design
      based on total scattered light intensity monitoring. 

PMID- 24663869
TI  - Silicon graphene Bragg gratings.
AB  - We propose the use of interleaved graphene sections on top of a silicon waveguide
      to implement tunable Bragg gratings. The filter central wavelength and bandwidth
      can be controlled changing the chemical potential of the graphene sections.
      Apodization techniques are also presented. 

PMID- 24663870
TI  - Nonlinear properties of AlGaAs waveguides in continuous wave operation regime.
AB  - Aluminum Gallium Arsenide (AlGaAs) is an attractive platform for the development
      of integrated optical circuits for all-optical signal processing thanks to its
      large nonlinear coefficients in the 1.55-MUm telecommunication spectral region.
      In this paper we discuss the results of the nonlinear continuous-wave optical
      characterization of AlGaAs waveguides at a wavelength of 1.55 MUm. We also report
      the highest value ever reported in the literature for the real part of the
      nonlinear coefficient in this material (Re(gamma) ~521 W(-1)m(-1)).

PMID- 24663871
TI  - GPC light shaper for speckle-free one- and two-photon contiguous pattern
      excitation.
AB  - Generalized Phase Contrast (GPC) is an efficient method for generating speckle
      free contiguous optical distributions useful in diverse applications such as
      static beam shaping, optical manipulation and recently, for excitation in two
      photon optogenetics. To fully utilize typical Gaussian lasers in such
      applications, we analytically derive conditions for photon efficient light
      shaping with GPC. When combined with the conditions for optimal contrast
      developed in previous works, our analysis further simplifies GPC's
      implementation. The results of our analysis are applied to practical illumination
      shapes, such as a circle and different rectangles commonly used in industrial or
      commercial applications. We also show simple and efficient beam shaping of
      arbitrary shapes geared towards biophotonics research and other contemporary
      applications. Optimized GPC configurations consistently give ~84% efficiency and
      ~3x intensity gain. Assessment of the energy savings when comparing to
      conventional amplitude masking show that ~93% of typical energy losses are saved
      with optimized GPC configurations. 

PMID- 24663872
TI  - Monte Carlo modeling of the dual-mode regime in quantum-well and quantum-dot
      semiconductor lasers.
AB  - Monte Carlo markovian models of a dual-mode semiconductor laser with quantum well
      (QW) or quantum dot (QD) active regions are proposed. Accounting for carriers and
      photons as particles that may exchange energy in the course of time allows an ab
      initio description of laser dynamics such as the mode competition and intrinsic
      laser noise. We used these models to evaluate the stability of the dual-mode
      regime when laser characteristics are varied: mode gains and losses, non
      radiative recombination rates, intraband relaxation time, capture time in QD,
      transfer of excitation between QD via the wetting layer... As a major result, a
      possible steady-state dual-mode regime is predicted for specially designed QD
      semiconductor lasers thereby acting as a CW microwave or terahertz-beating source
      whereas it does not occur for QW lasers. 

PMID- 24663873
TI  - Monte Carlo model of the depolarization of backscattered linearly polarized light
      in the sub-diffusion regime.
AB  - We present a predictive model of the depolarization ratio of backscattered
      linearly polarized light from spatially continuous refractive index media that is
      applicable to the sub-diffusion regime of light scattering. Using Monte Carlo
      simulations, we derived a simple relationship between the depolarization ratio
      and both the sample optical properties and illumination-collection geometry. Our
      model was validated on tissue simulating phantoms and found to be in good
      agreement. We further show the utility of this model by demonstrating its use for
      measuring the depolarization length from biological tissue in vivo. We expect our
      results to aid in the interpretation of the depolarization ratio from sub
      diffusive reflectance measurements. 

PMID- 24663874
TI  - Nonlinear excitation of polariton cavity modes in ZnO single nanocombs.
AB  - Tunable second harmonic (SH) polaritons have been efficiently generated in ZnO
      nanocombs, when the material is excited close to half of the band-gap. The
      nonlinear signal couples to the nanocavity modes, and, as a result, Fabry-Perot
      resonances with high Q factors of about 500 are detected. Due to the low
      effective volume of the confined modes, matter-light interaction is very much
      enhanced. This effect lowers the velocity of the SH polariton in the material by
      50 times, and increases the SH confinement inside the nanocavity due to this
      higher refractive index. We also show that the SH phase-matching condition is
      achieved through LO-phonon mediation. Finally, birrefringence of the crystal
      produces a strong SH intensity dependence on the input polarization, with a high
      polarization contrast, which could be used as a mechanism for light switching in
      the nanoscale. 

PMID- 24663875
TI  - Passive mode-locking performance of mixed Nd:La(0.11)Y(0.89)VO(4) crystal.
AB  - Passive mode locking of a diode pumped Nd:La(0.11)Y(0.89)VO(4) mixed crystal
      laser with a semiconductor saturable absorber mirror (SESAM) was experimentally
      investigated for the first time to our knowledge. Stable CW mode-locking has been
      achieved on both a-cut and c-cut mixed crystals. In case of the a-cut crystal,
      when a 2% output coupler (OC) was used, the shortest pulse obtained was 4.5 ps
      and the highest output power was 0.94 W, while when a 6% OC was used, the
      shortest pulse obtained was 6.8 ps and the highest output power was 5.16 W. In
      the latter case the optical conversion efficiency is 38% and the slope efficiency
      is 40.3%, respectively; with the c-cut crystal the shortest pulse achieved was
      5.5 ps. Moreover, simultaneous mode locking at two close wavelengths of 1064.3 nm
      and 1066.2 nm was observed on the c-cut crystal. The mode locked pulse beating
      generated temporal interference fringe of 0.5 THz repetition rate.

PMID- 24663876
TI  - One-time ray-tracing optimization method and its application to the design of an
      illuminator for a tube photo-bioreactor.
AB  - This study details a one-time ray-tracing optimization method for the
      optimization of LED illumination systems [S.-C. Chu and H.-L. Yang, "One-time ray
      tracing method for the optimization of illumination system," in Proceedings of
      International Conference on Optics in Precision Engineering and Nanotechnology
      (icOPEN, 2013), 87692M]. This method optimizes the performance of illumination
      systems by modifying the light source's radiant intensity distribution with a
      freeform lens, instead of modifying the illumination system structure. Because
      illumination system structures are unchanged in the design process, a designer
      can avoid the common problems faced when designing illumination systems, i.e.,
      the repeated and time-consuming ray-tracing process when optimizing the
      illumination system parameters. The easy approaches of the proposed optimization
      method to sample the target illumination areas and to divide the light source
      radiant intensity distribution make the proposed method can be applied to both
      direct-lit and non-direct-lit illumination systems. To demonstrate the proposed
      method, this study designs an illuminator for a tube photo-bioreactor using the
      proposed one-time ray-tracing method. A comparison shows that in the designing of
      the photo-bioreactor, tracing all rays one time requires about 13 hours, while
      optimizing the light source's radiant intensity distribution requires only about
      twenty minutes. The considerable reduction in the ray-tracing time shows that the
      proposed method is a fast and effective way to design illumination systems. 

PMID- 24663877
TI  - 3-D numerical simulation of Yb:YAG active slabs with longitudinal doping gradient
      for thermal load effects assessment.
AB  - We present a study of Yb:YAG active media slabs, based on a ceramic layered
      structure with different doping levels. We developed a procedure allowing 3D
      numerical analysis of the slab optical properties as a consequence of the thermal
      load induced by the pump process. The simulations are compared with a set of
      experimental results in order to validate the procedure. These structured
      ceramics appear promising in appropriate geometrical configurations, and thus are
      intended to be applied in the construction of High Energy Diode Pumped Solid
      State Laser (DPSSL) systems working in high repetition-rate pulsed regimes. 

PMID- 24663878
TI  - Wide wavelength selectable all-fiber thulium doped fiber laser between 1925 nm
      and 2200 nm.
AB  - We demonstrate an all-fiber Tm(3+)-doped silica fiber laser operating at a wide
      selectable wavelength range by using different fiber Bragg gratings (FBGs) as
      wavelength selection elements. With a specifically designed high reflective (HR)
      FBG and the fiber end as an output coupler, the lasing in the range from 1975 nm
      to 2150 nm with slope efficiency of >30% can be achieved. By employing a low
      reflective (LR) FBG as the output coupler, the obtainable wavelengths were
      extended to the range between 1925 nm and 2200 nm which is the reported longest
      wavelength from the Tm(3+)-doped silica fiber lasers. Furthermore, by employing a
      FBG array in the laser cavity and inducing bend loss between adjacent FBGs in the
      array, six switchable lasing wavelengths were achieved.

PMID- 24663879
TI  - An intracavity, frequency-doubled self-Raman vortex laser.
AB  - We demonstrate intracavity frequency doubling of the self-Raman field generated
      within a diode end-pumped, solid state Nd:GdVO(4) vortex laser. A maximum output
      power of 727 mW is generated at 586 nm with an overall diode-to-yellow conversion
      efficiency of 4%. Conservation of orbital angular momentum is observed under
      intracavity frequency doubling, with the topological charge of the yellow beam
      being twice that of the Stokes beam.

PMID- 24663880
TI  - Background clean-up in Brillouin microspectroscopy of scattering medium.
AB  - Brillouin spectroscopy is an emerging tool for microscopic optical imaging as it
      allows for non-contact, non-invasive, direct assessment of the elastic properties
      of materials. However, strong elastic scattering and stray light from various
      sources often contaminate the Brillouin spectrum. A molecular absorption cell was
      introduced into the virtually imaged phased array (VIPA) based Brillouin
      spectroscopy setup to absorb the Rayleigh component, which resulted in a
      substantial improvement of the Brillouin spectrum quality. 

PMID- 24663881
TI  - Grating-assisted enhanced optical transmission through a seamless gold film.
AB  - In this paper, we experimentally demonstrate enhanced optical transmission
      through a seamless gold film based on the grating-insulator-metal (GIM)
      architecture. The transmittance of this GIM structure reaches 40% at 930 nm,
      showing 3.7 dB and 9.1 dB increase compared with a bare gold film and a
      continuous metal-insulator-metal stack, respectively. The enhanced transmission
      is polarization-sensitive and robust for oblique incidence. With tunable
      transmission peaks, such a device exhibits great potential for applications in
      optical filtering, polarization detecting and further integration in
      optoelectronics system. 

PMID- 24663882
TI  - Experimental research and comparison of LDPC and RS channel coding in ultraviolet
      communication systems.
AB  - We have implemented a modified Low-Density Parity-Check (LDPC) codec algorithm in
      ultraviolet (UV) communication system. Simulations are conducted with measured
      parameters to evaluate the LDPC-based UV system performance. Moreover, LDPC (960,
      480) and RS (18, 10) are implemented and experimented via a non-line-of-sight
      (NLOS) UV test bed. The experimental results are in agreement with the simulation
      and suggest that based on the given power and 10(-3)bit error rate (BER), in
      comparison with an uncoded system, average communication distance increases 32%
      with RS code, while 78% with LDPC code.

PMID- 24663883
TI  - Computational superoscillation imaging beyond the Rayleigh limit from far-field
      measurements.
AB  - Far-field imaging beyond the Rayleigh limit is one of the most important
      challenges in optics, microwave, and ultrasonics. We propose a novel sparsity
      promoted super-oscillation imaging scheme for reconstructing more universal
      objects in subwavelength scales, which solves a weighted optimization problem
      constrained by lp-norm-based sparsity regularization (0<=p<=1). We demonstrate
      numerically that the proposed imaging technique improves the resolution related
      to existing approaches remarkably for the case of very high signal-to-noise ratio
      (SNR), including the traditional super-oscillation imaging and sparsity-based
      super-resolution imaging. The standard superoscillation based super-resolution
      imaging approach can be regarded as the first-iteration solution of the proposed
      scheme. Numerical results for one- and two-dimensional super-resolution imaging
      are presented for validation.

PMID- 24663884
TI  - Observation of vector- and scalar-pulse in a nanotube-mode-locked fiber laser.
AB  - We report the experimental observations of vector pulse trapping and scalar
      dissipative soliton in a compact nanotube-mode-locked all-fiber laser for the
      first time to our best knowledge. The vector pulse exhibits a smooth Gaussian
      spectral profile without any sidebands. Although two orthogonally polarized
      components of the vector pulse have different central wavelengths, they
      copropagate as a unit in the laser cavity with the same speed. The scalar
      dissipative soliton shows a rectangular spectrum with pulse duration of ~13 ps,
      and can be compressed to ~320 fs external to the cavity. This flexible laser
      provides stable, ultrashort vector- and scalar-pulsed sources, which is
      convenient and attractive for practical applications. 

PMID- 24663885
TI  - 4-lambda InGaAsP-Si distributed feedback evanescent lasers with varying silicon
      waveguide width.
AB  - A four-wavelength silicon hybrid laser array operating at room temperature is
      realized by evanescently coupling the optical gain of InGaAsP multi-quantum wells
      to the silicon waveguides of varying widths and patterned with distributed
      feedback gratings based on selective-area metal bonding technology. The lasers
      have emission peaks between 1539.9 and 1546.1 nm with a wavelength spacing of
      about 2.0 nm. The single laser has a typical threshold current of 50 mA and side
      mode suppression ratio of 20 dB. The silicon waveguides are fabricated simply by
      standard photolithography and holographic lithography which are CMOS compatible. 

PMID- 24663886
TI  - Sparsely sampled Fourier ptychography.
AB  - Fourier ptychography (FP) is an imaging technique that applies angular diversity
      functions for high-resolution complex image recovery. The FP recovery routine
      switches between two working domains: the spectral and spatial domains. In this
      paper, we investigate the spectral-spatial data redundancy requirement of the FP
      recovery process. We report a sparsely sampled FP scheme by exploring the
      sampling interplay between these two domains. We demonstrate the use of the
      reported scheme for bypassing the high-dynamic-range combination step in the
      original FP recovery routine. As such, it is able to shorten the acquisition time
      of the FP platform by ~50%. As a special case of the sparsely sample FP, we also
      discuss a sub-sampled scheme and demonstrate its application in solving the pixel
      aliasing problem plagued in the original FP algorithm. We validate the reported
      schemes with both simulations and experiments. This paper provides insights for
      the development of the FP approach. 

PMID- 24663887
TI  - Switchable beaming from a nanoslit with metallic gratings controlled by the phase
      difference between incident beams.
AB  - We propose a switching method for optical beaming generated from a metal slit
      surrounded by surface gratings. The principle of the method is based on the
      interference of diffracted surface plasmon polaritons from the gratings which are
      controlled by the relative phases of two oblique incident beams that are
      illuminated on the metal slit. By adjusting the relative position of the
      interference pattern of the incident beams with respect to the metal slit,
      beaming from the proposed structure can be switched from the on- to the off-mode
      by virtue of the change in the symmetry of the generated surface plasmon
      polaritons. An experimental demonstration of the method is presented in which an
      electrically controlled interferometric configuration is used. 

PMID- 24663888
TI  - Image fusion using wavelet transform and its application to asymmetric
      cryptosystem and hiding.
AB  - Image fusion is a popular method which provides better quality fused image for
      interpreting the image data. In this paper, color image fusion using wavelet
      transform is applied for securing data through asymmetric encryption scheme and
      image hiding. The components of a color image corresponding to different
      wavelengths (red, green, and blue) are fused together using discrete wavelet
      transform for obtaining a better quality retrieved color image. The fused color
      components are encrypted using amplitude- and phase-truncation approach in
      Fresnel transform domain. Also, the individual color components are transformed
      into different cover images in order to result disguising information of input
      image to an attacker. Asymmetric keys, Fresnel propagation parameters, weighing
      factor, and three cover images provide enlarged key space and hence enhanced
      security. Computer simulation results support the idea of the proposed fused
      color image encryption scheme. 

PMID- 24663889
TI  - Compressive and tensile strain sensing using a polymer planar Bragg grating.
AB  - A polymer planar Bragg grating sensor is used for measuring both mechanical
      compressive and tensile strain. The planar waveguide with integrated Bragg
      grating is fabricated in bulk Polymethylmethacrylate in a single writing step
      using combined amplitude and phase mask technique. After butt coupling of a
      single-mode optical fiber the planar structure can be applied for measuring both
      mechanical tensile and compressive strain alongside the integrated waveguide
      without the need of further modifications. In this respect, we particularly
      report for the first time compressive strain measurements using a polymer Bragg
      grating. Furthermore, the sensitivity of the sensor against tensile and
      compressive strain, its reproducibility and hysteresis are investigated and
      discussed. 

PMID- 24663890
TI  - Optimizing detection limits in whispering gallery mode biosensing.
AB  - A theoretical analysis of detection limits in swept-frequency whispering gallery
      mode biosensing modalities is presented based on application of the Cramer-Rao
      lower bound. Measurement acuity factors are derived assuming the presence of
      uncoloured and 1/ f Gaussian technical noise. Frequency fluctuations, for example
      arising from laser jitter or thermorefractive noise, are also considered.
      Determination of acuity factors for arbitrary coloured noise by means of the
      asymptotic Fisher information matrix is highlighted. Quantification and
      comparison of detection sensitivity for both resonance shift and broadening
      sensing modalities are subsequently given. Optimal cavity and coupling geometries
      are furthermore identified, whereby it is found that slightly under-coupled
      cavities outperform critically and over coupled ones. 

PMID- 24663891
TI  - Non-null testing for aspheric surfaces using elliptical sub-aperture stitching
      technique.
AB  - We propose an elliptical sub-aperture stitching (ESAS) method to measure the
      aspheric surfaces. In our method, the non-null configuration is used to overcome
      the disadvantages of the null testing. By adding the dynamic tilt, the different
      local nearly null fringe patterns are obtained and the corresponding phase data
      in the elliptical masks is extracted with negligible retrace errors. In order to
      obtain the full aperture result, a stitching algorithm is developed to stitch all
      the phase data together. We firstly show the principle of our method. Then the
      performance of the proposed method is analyzed by simulation experiments. In the
      end, practical examples are given to demonstrate the correctness of the proposed
      method. The stitching result shows a good agreement with the full-aperture null
      testing result. 

PMID- 24663892
TI  - Photonic-assisted microwave phase shifter using a DMZM and an optical bandpass
      filter.
AB  - We propose and demonstrate a photonic-assisted wideband 360 degrees  microwave
      phase shifter based on a conventional dual-drive Mach-Zehnder modulator (DMZM)
      and an optical bandpass filter (OBPF). The two arms of the DMZM are driven by the
      fundamental microwave signal to be phase shifted and its frequency doubled
      component, respectively. The OBPF followed after the DMZM is used to remove the
      optical carrier and the sidebands at either side of the optical carrier. As a
      result, only two sidebands corresponding to the fundamental microwave signal and
      its frequency doubled component, respectively, are left. Moreover, the phase
      shift between the two sidebands can be continuously tunable by adjusting the bias
      voltage of the DMZM. This phase shift is mapped to the fundamental microwave
      signal which is recovered by beating the two sidebands in a photodetector (PD).
      The proposed approach is theoretically analyzed and experimentally verified. 

PMID- 24663893
TI  - Fresnel coherent diffractive imaging of elemental distributions in nanoscale
      binary compounds.
AB  - We report quantitative determination of elemental distribution in binary
      compounds with nano meter scale spatial resolution using x-ray Fresnel coherent
      diffractive imaging (FCDI). We show that the quantitative magnitude and phase
      values of the x-ray wave exiting an object determined by FCDI can be utilized to
      obtain full-field atomic density maps of each element independently. The proposed
      method was demonstrated by reconstructing the density maps of Pt and NiO in a Pt
      NiO binary compound with about 18 nm spatial resolution. 

PMID- 24663894
TI  - Passive synchronization of erbium and thulium doped fiber mode-locked lasers
      enhanced by common graphene saturable absorber.
AB  - In this work we present for the first time, to the best of our knowledge, a
      passively synchronized thulium (Tm) and erbium (Er) doped fiber laser mode-locked
      by a common graphene saturable absorber (GSA). The laser consists of two ring
      resonators combined with a 90 cm long common fiber branch incorporating the
      saturable absorber (SA). Such laser generates optical solitons centered at 1558.5
      nm and 1938 nm with pulse durations of 915 fs and 1.57 ps, respectively. Both
      laser loops were passively synchronized at repetition frequency of 20.5025 MHz by
      nonlinear interaction (cross phase modulation, XPM) in common fiber branch
      between generated pulses. The maximum cavity mismatch of the Er-laser in
      synchronization regime was 0.78 mm. The synchronization mechanism was also
      investigated. We demonstrate that the third order nonlinearities of graphene
      enhance the synchronization range. In our case the range was increased about 85%.
      The integrated RMS timing jitter between the synchronized pulses was 67 fs. 

PMID- 24663895
TI  - Generation of few-cycle infrared pulses from a degenerate dual-pump OPCPA.
AB  - A degenerate dual-pump optical parametric chirped-pulse amplifier (OPCPA) for
      generation of few-cycle intense pulses centered at 1.6 MUm is theoretically
      investigated. By adding the optimized linear chirp to the two pump pulses from
      Ti:sapphire source and carefully adjusting the delays between the two pumps and
      seed, the long- and short-wavelength components of the seed pulse are efficiently
      amplified during the parametric process. Our simulations show that a broadband
      spectrum spanning from 1.3 MUm to 2.1 MUm is attained with a conversion
      efficiency of 22.6%. Signal pulse with a near transform-limited (TL) duration of
      10.1 fs can be achieved by simply removing the linear chirp from the output
      signal. Besides, the compressed signal beam manifests good quality both
      spectrally and temporally, which allows tightly focusing the signal beam for
      further use. 

PMID- 24663896
TI  - Gain switch laser based on micro-structured Yb-doped active fiber.
AB  - In this paper a near infrared gain-switched fiber laser based on oscillator stage
      only design with high peak power is presented. Output pulses reached 2.3 kW of
      peak power and duration of less than 60 ns. The dependence of the laser pulse
      duration on operation parameters was measured and theoretically explained. As the
      setup is based on flexible micro structured single polarization fiber, the laser
      output exhibits high polarization extinction ratio. Due to the narrow output
      spectrum the setup is suitable for second harmonic generation. 

PMID- 24663897
TI  - Graphene mode-locked Cr:ZnS laser with 41 fs pulse duration.
AB  - We report the ultrashort-pulse Cr:ZnS laser mode-locked by graphene-based
      saturable absorber mirror. Using the combination of bulk material and a chirped
      mirror, we demonstrate the shortest reported so far mid-IR pulses of only 5.1
      optical cycles (41 fs) centered at 2.4 um with 190 nm spectral bandwidth. The
      pulse spectrum almost completely fills the water-free atmospheric window. The
      output parameters reach 2.3 nJ pulse energy and 250 mW average output power at
      108 MHz repetition rate. 

PMID- 24663899
TI  - Large parallelization of STED nanoscopy using optical lattices.
AB  - As a scanning microscope, STimulated Emission Depletion (STED) nanoscopy needs
      parallelization for fast wide-field imaging. Using well-designed optical lattices
      for depletion together with wide-field excitation and a fast camera for
      detection, we achieve large parallelization of STED nanoscopy. Wide field of view
      super-resolved images are acquired by scanning over a single unit cell of the
      optical lattice, which can be as small as 290 nm * 290 nm. Optical Lattice STED
      (OL-STED) imaging is demonstrated with a resolution down to 70 nm at 12.5 frames
      per second. 

PMID- 24663898
TI  - X-ray micro-modulated luminescence tomography (XMLT).
AB  - Imaging depth of optical microscopy has been fundamentally limited to millimeter
      or sub-millimeter due to strong scattering of light in a biological sample. X-ray
      microscopy can resolve spatial details of few microns deep inside a sample but
      contrast resolution is inadequate to depict heterogeneous features at cellular or
      sub-cellular levels. To enhance and enrich biological contrast at large imaging
      depth, various nanoparticles are introduced and become essential to basic
      research and molecular medicine. Nanoparticles can be functionalized as imaging
      probes, similar to fluorescent and bioluminescent proteins. LiGa(5)O(8):Cr(3+)
      nanoparticles were recently synthesized to facilitate luminescence energy storage
      with x-ray pre-excitation and subsequently stimulated luminescence emission by
      visible/near-infrared (NIR) light. In this paper, we propose an x-ray micro
      modulated luminescence tomography (XMLT, or MLT to be more general) approach to
      quantify a nanophosphor distribution in a thick biological sample with high
      resolution. Our numerical simulation studies demonstrate the feasibility of the
      proposed approach.

PMID- 24663900
TI  - Bimetal coated optical fiber sensors based on surface plasmon resonance induced
      change in birefringence and intensity.
AB  - We present a surface plasmon resonance (SPR) based multimode fiber sensor with
      non-golden bimetallic coating. Our detection scheme used, which is capable of
      measuring the combined effects of SPR-induced birefringence and intensity
      changes, supported the minimum resolvable refractive index (RI) of 5.8 * 10(-6)
      RIU with the operating RI range of 0.05 to be experimentally obtained at a single
      wavelength (632.8 nm) without non-spectroscopic techniques. The asymmetric
      profile of the thickness of the bimetal coating on the fiber core together with
      the inherent range of incidence angle for multimode propagation also contributed
      to the wide operating range. The SPR fiber device with the detection scheme
      demonstrated will be likely to be developed as a real-time label-free and highly
      sensitive diagnostic device of a wide operating range for biomedical and
      biochemical applications in a portable format.

PMID- 24663901
TI  - A compact source condition for modelling focused fields using the pseudospectral
      time-domain method.
AB  - The pseudospectral time-domain (PSTD) method greatly extends the physical volume
      of biological tissue in which light scattering can be calculated, relative to the
      finite-difference time-domain (FDTD) method. We have developed an analogue of the
      total-field scattered-field source condition, as employed in FDTD, for
      introducing focussed illuminations into PSTD simulations. This new source
      condition requires knowledge of the incident field, and applies update equations,
      at a single plane in the PSTD grid. Numerical artifacts, usually associated with
      compact PSTD source conditions, are minimized by using a staggered grid. This
      source condition's similarity with that used by the FDTD suggests a way in which
      existing FDTD codes can be easily adapted to PSTD codes. 

PMID- 24663902
TI  - Nonlinear dynamics in integrated coupled DFB lasers with ultra-short delay.
AB  - We report rich nonlinear dynamics in integrated coupled lasers with ultra-short
      coupling delay. Mutually stable locking, period-1 oscillation, frequency locking,
      quasi-periodicity and chaos are observed experimentally. The dynamic behaviors
      are reproduced numerically by solving coupled delay differential equations that
      take the variation of both frequency detuning and coupling phase into account.
      Moreover, it is pointed out that the round-trip frequency is not involved in the
      above nonlinear dynamical behaviors. Instead, the relationship between the
      frequency detuning Deltanu and the relaxation oscillation frequency nur under
      mutual injection are found to be critical for the various observed dynamics in
      mutually coupled lasers with very short delay. 

PMID- 24663903
TI  - Aberration measurement technique based on an analytical linear model of a through
      focus aerial image.
AB  - We propose an in situ aberration measurement technique based on an analytical
      linear model of through-focus aerial images. The aberrations are retrieved from
      aerial images of six isolated space patterns, which have the same width but
      different orientations. The imaging formulas of the space patterns are
      investigated and simplified, and then an analytical linear relationship between
      the aerial image intensity distributions and the Zernike coefficients is
      established. The linear relationship is composed of linear fitting matrices and
      rotation matrices, which can be calculated numerically in advance and utilized to
      retrieve Zernike coefficients. Numerical simulations using the lithography
      simulators PROLITH and Dr.LiTHO demonstrate that the proposed method can measure
      wavefront aberrations up to Z(37). Experiments on a real lithography tool confirm
      that our method can monitor lens aberration offset with an accuracy of 0.7 nm.

PMID- 24663904
TI  - 90-fs diode-pumped Yb:CLNGG laser mode-locked using single-walled carbon nanotube
      saturable absorber.
AB  - A diode-pumped Yb:CLNGG laser is mode-locked with a single-walled carbon nanotube
      saturable absorber (SWCNT-SA) for the first time. Pulse durations as short as 90
      fs are obtained at ~1049 nm with 0.4% output coupler, the shortest pulses to our
      knowledge for a diode-pumped 1-um laser applying SWCNTs as saturable absorber.
      Using 3% output coupler, the maximum average output power reached 90 mW at a
      repetition frequency of 83 MHz. 

PMID- 24663905
TI  - Three-dimensional tracking of a single fluorescent nanoparticle using four-focus
      excitation in a confocal microscope.
AB  - We report high sensitivity detection and tracking of a single fluorescent
      nanoparticle in solution by use of four alternately pulsed laser diodes for
      fluorescence excitation in a confocal microscope. Slight offsets between the
      centers of the overlapping laser foci together with time-resolved photon counting
      enable sub-micron precision position measurements. Real-time correction for
      diffusional motion with a xyz-piezo stage then enables tracking of a nanoparticle
      with diffusivity up to ~12 MUm(2) s(-1). Fluorescence correlation spectroscopy
      and calibration measurements indicate a net fluorescence photon detection
      efficiency of ~6-9%, comparable to that of an optimized single-molecule
      microscope.

PMID- 24663906
TI  - Linewidth enhancement factor in semiconductor lasers subject to various external
      optical feedback conditions.
AB  - The linewidth enhancement factor alpha of a semiconductor laser under the
      influences of optical feedback with different feedback strengths, external cavity
      lengths, and feedback phases are studied both experimentally and theoretically.
      The value of alpha is determined from the minimum of the Hopf bifurcation curve
      when the laser is subject to both optical feedback and optical injection. In the
      experiment, a pellicle beamsplitter mounted on a PZT stage placed on a linear
      translation stage is used as the reflector, where the external cavity length can
      be adjusted continuously from the long cavity regime to the short cavity regime
      with phase accuracy. With a moderate feedback strength, alpha is found to
      increase as the feedback strength increases. Moreover, while alpha is insensitive
      to the feedback phase in the long cavity regime, it can be tuned continuously in
      the short cavity regime when varying the phase. A normalized variation range of
      21.59% is obtained experimentally at an external cavity length of 1.5 cm, which
      can be further enhanced by shortening the external cavity. To the best of our
      knowledge, this is the first detailed study of alpha from the long to the short
      cavity regime in a semiconductor laser subject to optical feedback. More
      particularly, the continuous tuning of alpha under phase variation is
      demonstrated the first time. 

PMID- 24663907
TI  - Photoluminescence in Ga/Bi co-doped silica glass.
AB  - Bismuth-Gallium co-doped silica glass fiber preform was prepared from nano-porous
      silica xerogels using a conventional solution doping technique with a
      heterotrinuclear complex and subsequent sintering. Ga-connected optical Bismuth
      active center (BAC) was identified as the analogue of Al-connected BAC. Visible
      and infrared photoluminescence (PL) were investigated in a wide temperature range
      of 1.46 - 300 K. Based on the results of the continuous wave (CW) and time
      resolved (TR) spectroscopy we identify the centers emitting in the spectral
      region of 480 - 820 nm as Bi(+) ions. The near infrared (NIR) PL around 1100 nm
      consists of two bands. While the first one can be ascribed to the transition in
      Bi(+) ion, the second band is presumably associated to defects. We put in
      evidence the energy transfer (ET) between Bi(+) ions and the second NIR emitting
      center via quadrupole-quadrupole and dipole-quadrupole mechanisms of
      interactions. Finally, we propose the energy level diagram of Bi(+) ion
      interacting with this defect.

PMID- 24663908
TI  - Spectroscopic measurement of absorptive thin films by spectral-domain optical
      coherence tomography.
AB  - A non-invasive method for measuring the refractive index, extinction coefficient
      and film thickness of absorptive thin films using spectral-domain optical
      coherent tomography is proposed, analyzed and experimentally demonstrated. Such
      an optical system employing a normal-incident beam of light exhibits a high
      spatial resolution. There are no mechanical moving parts involved for the
      measurement except the transversal scanning module for the measurement at various
      transversal locations. The method was experimentally demonstrated on two
      absorptive thin-film samples coated on transparent glass substrates. The
      refractive index and extinction coefficient spectra from 510 to 580 nm wavelength
      range and film thickness were simultaneously measured. The results are presented
      and discussed. 

PMID- 24663909
TI  - Impact of ALD grown passivation layers on silicon nitride based integrated optic
      devices for very-near-infrared wavelengths.
AB  - A CMOS compatible post-processing method to reduce optical losses in silicon
      nitride (Si(3)N(4)) integrated optical waveguides is demonstrated. Using thin
      layer atomic layer deposition (ALD) of aluminum oxide (Al(2)O(3)) we demonstrate
      that surface roughness can be reduced. A 40 nm thick Al(2)O(3) layer is deposited
      by ALD over Si(3)N(4) based strip waveguides and its influence on the surface
      roughness and the waveguide loss is studied. As a result, an improvement in the
      waveguide loss, from very high loss (60 dB/cm) to low-loss regime (~5 dB/cm) is
      reported for a 220 nm x 500 nm Si(3)N(4) wire at 900 nm wavelength. This opens
      prospects to implement very low loss waveguides.

PMID- 24663910
TI  - Analytical and experimental performance evaluation of an integrated Si-photonic
      balanced coherent receiver in a colorless scenario.
AB  - We study analytically and experimentally the performance limits of a Si-photonic
      (SiP) balanced coherent receiver (CRx) co-packaged with transimpedance amplifiers
      (TIAs) in a colorless WDM scheme. Firstly, the CRx architecture is depicted and
      characterization results are presented. Secondly, an analytical expression for
      the signal-to-noise ratio (SNR) at the CRx output is rigorously developed and
      various noise sources in the context of colorless reception are outlined.
      Thirdly, we study experimentally the system-level CRx performance in colorless
      reception of 16 * 112 Gbps PDM-QPSK WDM channels. Using a 15.5 dBm local
      oscillator (LO) power, error free transmissions over 4800 and 4160 km at received
      powers of -3 and -21 dBm per channel, respectively, were achieved in a fully
      colorless and preamplifierless reception. Next, a set of measurements on one of
      the center WDM channels is performed where the LO power, received signal power,
      distance, and number of channels presented to the CRx are swept to evaluate the
      performance limits of colorless reception. Results reveal that the LO beating
      with optical noise incoming with the signal is a dominant noise source regardless
      of received signal power. In the high received signal power regime (~0
      dBm/channel), the self-beat noise from out-of-band (OOB) channels is an
      additional major noise source especially for small LO-to-signal power ratio,
      short reach and large number of OOB channels. For example, at a received signal
      power of 0 dBm/channel after 1600 km transmission, the SNR difference between the
      fully filtered and colorless scenarios, where 1 and 16 channels are passed to the
      CRx respectively, grows from 0.5 to 3.3 dB as the LO power changes from 12 to 0
      dBm. For low received power (~-12 dBm/channel), the effect of OOB channels
      becomes minor while the receiver shot and thermal noises become more significant.
      We identify the common mode rejection ratio (CMRR) and sensitivity as the two
      important CRx specifications that impact the performance at high and low received
      signal power regimes, respectively. Finally, an excellent match between
      experimental and analytical SNRs is proven after the derived SNR model is fitted
      to the experimental data in a least-squares sense. The model is then used to
      predict that the CRx can operate colorlessly for a fully populated WDM spectrum
      with 80 channels provided that the LO-to-signal power ratio is properly set. 

PMID- 24663911
TI  - Noise suppressed optical diffraction tomography with autofocus correction.
AB  - We propose a novel tomographic measurement approach that enables a noise
      suppressed characterization of microstructures. The idea of this work is based on
      a finding that coherent noise in the input phase data generates an artificial
      circular structure whose magnitude is the highest at the centre of tomographic
      reconstruction. This method decreases the noise level by applying an
      unconventional tomographic measurement configuration with an object deliberately
      shifted with respect to the rotation axis. This enables a spatial separation
      between the reconstructed sample structure and the area of the largest refractive
      index perturbations. The input phase data defocusing that is a by-product of the
      introduced modification is numerically corrected with an automatic focus
      correction algorithm. The proposed method is validated with simulations and
      experimental measurements of an optical microtip. 

PMID- 24663912
TI  - 7-ps optical pulse generation from a 1064-nm gain-switched laser diode and its
      application for two-photon microscopy.
AB  - In this study, we investigated the picosecond optical pulse generation from a
      1064-nm distributed feedback laser diode under strong gain switching. The
      spectrum of the generated optical pulses was manipulated in two different ways:
      (i) by extracting the short-wavelength components of the optical pulse spectrum
      and (ii) by compensating for spectral chirping in the extracted mid-spectral
      region. Both of these methods shortened the optical pulse duration to
      approximately 7 ps. These optical pulses were amplified to over 20-kW peak power
      for two-photon microscopy. We obtained clear two-photon images of neurons in a
      fixed brain slice of H-line mouse expressing enhanced yellow fluorescent protein.
      Furthermore, a successful experiment was also confirmed for in vivo deep region H
      line mouse brain neuron imaging. 

PMID- 24663913
TI  - Surface-plasmon-polariton whispering-gallery mode analysis of the graphene
      monolayer coated InGaAs nanowire cavity.
AB  - In this article, we proposed and numerically studied the surface plasmon
      polariton whispering gallery mode properties of the graphene coated InGaAs
      nanowire cavity. The quality factor and the mode area were investigated as a
      function of the chemical potential, the cavity radius and the wavelength. A high
      cavity quality factor of 235 is predicted for a 5 nm radius cavity, accompanied
      by a mode area as small as3.75*10(-5)(lambda(0))(2), when the chemical potential
      is 1.2 eV. The proposed structure offers a potential solution to high density
      integration of the nanophotonic devices with an ultra-compact footprint.

PMID- 24663914
TI  - Noise beating in hybrid phase-sensitive amplifier systems.
AB  - We investigate the effect of noise loading in a hybrid phase-sensitive amplifier
      system, analyzing the effect of noise beating between the signal and idler waves
      coupled in a parametric amplifier. Through analyzing input and output optical
      signal to noise ratios, we find that system performance of a phase-sensitive
      amplifier is 3 to 6 dB improved over a phase-insensitive amplifier, depending on
      the ratio of loaded noise power to that of vacuum fluctuations. 

PMID- 24663915
TI  - Metal nanodisk hybrid plasmonic resonator on dielectric substrate for relieved
      fabrication complexity.
AB  - We propose a metal nanodisk hybrid plasmonic resonator (HPR), which consists of a
      metallic nanodisk on top of a dielectric slab. In contrast to the previously
      studied plasmonic resonator structures based on metal substrates such as the
      nanopatch resonator, the fabrication process of the proposed resonator is much
      easier because of a dielectric substrate. The performance of the proposed
      resonator has been theoretically investigated and compared to the previously
      studied structures. It has been shown that the performance of the proposed
      resonator is superior to that of the nanopatch resonator and comparable to that
      of a hybrid resonator based on a metal substrate. 

PMID- 24663916
TI  - Compact two-mode (de)multiplexer based on symmetric Y-junction and multimode
      interference waveguides.
AB  - A compact two-mode (de)multiplexer [(DE)MUX] based on symmetric Y-junction and
      multimode interference (MMI) waveguides was designed by 3D beam propagation
      method (BPM). The phase evolution in the structure was discussed in detail.
      Simulations show that the optical bandwidth is as large as 100 nm (1500 nm ~1600
      nm). The two-mode (DE)MUX is very compact compared with the other kind of mode
      (DE)MUX. The length of the structure is only 48.8 MUm. Simulation also shows the
      fabrication tolerance is as large as +/- 75 nm. 

PMID- 24663918
TI  - Elimination of light leakage over the entire viewing cone in a homogeneously
      aligned liquid crystal cell.
AB  - We propose an optical compensation scheme that uses uniaxial films for perfect
      elimination of light leakage over the entire viewing cone in a homogeneously
      aligned liquid crystal cell. Uniaxial films with different dispersion
      characteristics are used so that they can compensate one another to achieve
      achromatic optical compensation. Owing to the rotational symmetry of the
      polarization change on the S(2)-S(3) plane of the Poincare sphere, we can
      eliminate the light leakage at all azimuth angles. The contrast ratio of the
      proposed configuration for white light is higher than 3000:1 at a polar angle of
      +/- 85 degrees , irrespective of the azimuth angle.

PMID- 24663917
TI  - Model for estimating the penetration depth limit of the time-reversed
      ultrasonically encoded optical focusing technique.
AB  - The time-reversed ultrasonically encoded (TRUE) optical focusing technique is a
      method that is capable of focusing light deep within a scattering medium. This
      theoretical study aims to explore the depth limits of the TRUE technique for
      biological tissues in the context of two primary constraints - the safety limit
      of the incident light fluence and a limited TRUE's recording time (assumed to be
      1 ms), as dynamic scatterer movements in a living sample can break the time
      reversal scattering symmetry. Our numerical simulation indicates that TRUE has
      the potential to render an optical focus with a peak-to-background ratio of ~2 at
      a depth of ~103 mm at wavelength of 800 nm in a phantom with tissue scattering
      characteristics. This study sheds light on the allocation of photon budget in
      each step of the TRUE technique, the impact of low signal on the phase
      measurement error, and the eventual impact of the phase measurement error on the
      strength of the TRUE optical focus. 

PMID- 24663919
TI  - Lissajous fiber scanning for forward viewing optical endomicroscopy using
      asymmetric stiffness modulation.
AB  - We report a fully packaged and compact forward viewing endomicroscope by using a
      resonant fiber scanner with two dimensional Lissajous trajectories. The fiber
      scanner comprises a single mode fiber with additional microstructures mounted
      inside a piezoelectric tube with quartered electrodes. The mechanical cross
      coupling between the transverse axes of a resonant fiber with a circular cross
      section was completely eliminated by asymmetrically modulating the stiffness of
      the fiber cantilever with silicon microstructures and an off-set fiber fragment.
      The Lissajous fiber scanner was fully packaged as endomicroscopic catheter
      passing through the accessory channel of a clinical endoscope and combined with
      spectral domain optical coherence tomography (SD-OCT). Ex-vivo 3D OCT images were
      successfully reconstructed along Lissajous trajectory. The preview imaging
      capability of the Lissajous scanning enables rapid 3D imaging with high temporal
      resolution. This endoscopic catheter provides many opportunities for on-demand
      and non-invasive optical biopsy inside a gastrointestinal endoscope. 

PMID- 24663920
TI  - Experimental demonstration of a Laguerre-Gaussian correlated Schell-model vortex
      beam.
AB  - Laguerre-Gaussian correlated Schell-model (LGCSM) vortex beam is introduced as an
      extension of LGCSM beam which was proposed [Opt. Lett.38, 91 (2013)Opt. Lett.38,
      1814 (2013)] just recently. Explicit formula for a LGCSM vortex beam propagating
      through a stigmatic ABCD optical system is derived, and the propagation
      properties of such beam in free space and the focusing properties of such beam
      are studied numerically. Furthermore, we carry out experimental generation of a
      LGCSM vortex beam, and studied its focusing properties. It is found that the
      propagation and focusing properties of a LGCSM vortex beam are different from
      that of a LGCSM beam, and we can shape the beam profile of a LGCSM vortex at the
      focal plane (or in the far field) by varying its initial spatial coherence. Our
      experimental results are consistent with the theoretical predictions, and our
      results will be useful for particle trapping. 

PMID- 24663921
TI  - High fluence laser damage precursors and their mitigation in fused silica.
AB  - The use of any optical material is limited at high fluences by laser-induced
      damage to optical surfaces. In many optical materials, the damage results from a
      series of sources which initiate at a large range of fluences and intensities.
      Much progress has been made recently eliminating silica surface damage due to
      fracture-related precursors at relatively low fluences (i.e., less than 10
      J/cm(2), when damaged by 355 nm, 5 ns pulses). At higher fluence, most materials
      are limited by other classes of damage precursors which exhibit a strong
      threshold behavior and high areal density (>10(5) cm(-2)); we refer to these
      collectively as high fluence precursors. Here, we show that a variety of
      nominally transparent materials in trace quantities can act as surface damage
      precursors. We show that by minimizing the presence of precipitates during
      chemical processing, we can reduce damage density in silica at high fluence by
      more than 100 times while shifting the fluence onset of observable damage by
      about 7 J/cm(2). A better understanding of the complex chemistry and physics of
      cleaning, rinsing, and drying will likely lead to even further improvements in
      the damage performance of silica and potentially other optical materials.

PMID- 24663922
TI  - Study of filamentation threshold in zinc selenide.
AB  - The possibility of creating filaments with laser wavelengths ranging from 800 nm
      to 2.4 um was investigated using an OPA laser system. Zinc Selenide's (ZnSe)
      unique characteristics - small band gap E(gZnSe)=2.67eV and positive dispersion
      for this wavelength range - are well suited for filamentation study where multi
      photon absorption can be achieved with two to six photons.

PMID- 24663923
TI  - Multi-channel nonlinearity compensation of PDM-QPSK signals in dispersion-managed
      transmission using dispersion-folded digital backward propagation.
AB  - We demonstrate nonlinearity compensation of 37.5-GHz-spaced 128-Gb/s PDM-QPSK
      signals using dispersion-folded digital-backward-propagation and a spectrally
      sliced receiver that simultaneously receives three WDM signals, showing
      mitigation of intra-channel and inter-channel nonlinear effects in a 2560-km
      dispersion-managed TWRS-fiber link. Intra-channel and adjacent inter-channel
      nonlinear compensation gains when WDM channels are fully populated in the C-band
      are estimated based on the GN-model. 

PMID- 24663924
TI  - QCL-based nonlinear sensing of independent targets dynamics.
AB  - We demonstrate a common-path interferometer to measure the independent
      displacement of multiple targets through nonlinear frequency mixing in a quantum
      cascade laser (QCL). The sensing system exploits the unique stability of QCLs
      under strong optical feedback to access the intrinsic nonlinearity of the active
      medium. The experimental results using an external dual cavity are in excellent
      agreement with the numerical simulations based on the Lang-Kobayashi equations. 

PMID- 24663925
TI  - Blind deconvolution for spatial distribution of Kalpha emission from ultraintense
      laser-plasma interaction.
AB  - The spatial distributions of the Kalpha emission from foil targets irradiated
      with ultra-intensity laser pulses have been studied using the x-ray coded imaging
      technique. Due to the effect of hard x-ray background contamination, noise as
      well as imperfection of imaging system, it is hard to determine the PSF
      analytically or measure it experimentally. Therefore, we propose a blind
      deconvolution method to restore both the spatial distributions of the Kalpha
      emission and the system's PSF from the coded images based on the maximum
      likelihood scheme. Experimental restoration results from penumbral imaging and
      ring coded imaging demonstrated that both the structure integrity and the rich
      detail information can be well preserved. 

PMID- 24663926
TI  - Multi-component-intermodal-interference mechanism and characteristics of a long
      period grating assistant fluid-filled photonic crystal fiber interferometer.
AB  - A compact in-line modal interferometer based on a long period grating (LPG)
      inscribed in water-filled photonic crystal fiber (PCF) is proposed and
      demonstrated. The interferometer works from the interference between fundamental
      core mode and different vector components of LP(11) core mode. The LPG is
      especially inscribed to realize the energy exchange between the fundamental core
      mode and different vector components of LP(11) core mode in the PCF. We build a
      complete theoretical model and systematically analyze the multi-component
      intermodal-interference mechanism of the interferometer based on coupled-mode
      theory. Due to the asymmetric index distribution over the cross section of the
      PCF caused by CO(2)-laser side illumination, the dispersion curves and
      temperature sensitivities referring to different vector components of LP(11) core
      mode are quite different. Thus the interferometer is polarization-dependent and
      the adjacent interference fringes according to different components of LP(11)
      mode show greatly discrimination in sensitivities of temperature and strain,
      making it a good candidate for multiple physics parameters measurements.

PMID- 24663927
TI  - Photocurrent response of carbon nanotube-metal heterojunctions in the terahertz
      range.
AB  - We investigate the optoelectronic properties of a carbon nanotube (CNT)-metal
      heterostructure in the terahertz range. On the basis of terahertz time-domain
      spectroscopy characterization of a double-walled CNT (DWNT) film, we present and
      analyze the photocurrent measurement for a DWNT-nickel heterojunction illuminated
      by continuous-wave terahertz radiation. A significant current across the junction
      directly induced by terahertz excitation is observed and a negative
      photoconductivity behavior is found to occur in the device. The photocurrent
      shows a linear response to the bias voltage and the illumination power within the
      examined range. These phenomena support the feasibility of using CNT-metal
      heterojunctions as novel terahertz detectors. 

PMID- 24663928
TI  - High quality factor polymeric Fabry-Perot resonators utilizing a polymer
      waveguide.
AB  - Optical resonators are used in a variety of applications ranging from sensors to
      lasers and signal routing in high volume communication networks. Achieving a high
      quality (Q) factor is necessary for higher sensitivity in sensing applications
      and for narrow linewidth light emission in most lasing applications. In this
      work, we propose a new approach to achieve a very high Q-factor in polymeric
      Fabry-Perot resonators by conquering light diffraction inside the optical cavity.
      This can be achieved by inducing a refractive index feature inside the optical
      cavity that simply creates a waveguide between the two mirrors. This approach
      eliminates diffraction loss from the cavity and therefore the Q-factor is only
      limited by mirror loss and absorption. To demonstrate this claim, a device has
      been fabricated consisting of two dielectric Bragg reflectors with a 100 MUm
      layer of photosensitive polymer between them. The refractive index of this
      polymer can be modified utilizing standard photo-lithography processes. The
      measured finesse of the fabricated device was 692 and the Q-factor was 55000. 

PMID- 24663929
TI  - The role of spatial and temporal modes in pulsed parametric down-conversion.
AB  - We explore spatial correlations created by stimulated pair emission in frequency
      degenerate parametric down-conversion from a periodically poled KTP crystal
      pumped by ~2 ps duration laser pulses. The ratio of stimulated pairs over
      spontaneous pairs reaches as high 0.8 in the experiment. This ratio is a direct
      measure of the total number of modes relevant to the down-conversion process. We
      identify a universal curve for this ratio that accounts for the effect of the
      focused pump, introducing a coherence diameter r(0) related to the diffraction
      limited size of the pump beam in the far-field. Measurements of the spatial
      correlations of the PDC light for longer crystals and tight focusing conditions
      show that the description given in terms of a universal curve is surprisingly
      robust and breaks down only for a laser beam focussed to a waist smaller than 40
      MUm in a 2 mm long PPKTP crystal.

PMID- 24663930
TI  - Design and numerical analysis of surface plasmon-enhanced fin Ge-Si light
      emitting diode.
AB  - Heavily-doped strained germanium (Ge) can emit light efficiently thanks to its
      pseudo direct band gap characteristic. This makes Ge a good candidate for on-chip
      monolithic light sources in silicon (Si) photonics systems. We propose fin-shaped
      Ge-Si heterojunction light-emitting diode (LED) with metal gates, which can
      enhance light emission by coupling with surface plasmon resonant modes and
      modulate light emission from the LED. We verify these two aspects through
      numerical analysis and device simulations. We develop the method to find the
      optimal device structure and specific device dimensions to maximize the
      spontaneous emission rate enhancement. Also we find that the LED can be modulated
      by a gate voltage bias. 

PMID- 24663931
TI  - Quantitative evaluation of in-line x-ray phase contrast for a class of edge
      objects.
AB  - In order to quantify the effect of phase contrast on X-ray image formation, the
      theory of statistical decision making has been applied to a binary classification
      task between two signals known exactly, namely, a phase-contrast image (that
      combines both the absorption and phase contrast) and the corresponding
      hypothetical pure absorption image that would be obtained under the same imaging
      conditions but without diffraction/refraction effects. The signal-to-noise ratio
      (SNR) for two widely used observers, including the ideal observer (also known as
      the prewhitening matched filter) and a non-ideal observer (the non-prewhitening
      matched filter) has been estimated in the case of in-line phase-contrast imaging,
      thus providing a figure-of-merit for the optimisation of the imaging conditions.
      A broad class of edge objects has been investigated and simple analytical
      expressions for the corresponding SNRs have been obtained and discussed. 

PMID- 24663932
TI  - All-optically reconfigurable and tunable fiber surface grating for in-fiber
      devices: a wideband tunable filter.
AB  - A fiber surface grating (FSG) formed from a photosensitive liquid crystal hybrid
      (PLCH) film overlaid on a side-polished fiber (SPF) is studied and has been
      experimentally shown to be able to function as an all-optically reconfigurable
      and tunable fiber device. The device is all-optically configured to be a short
      period fiber surface grating (SPFSG) when a phase mask is used, and then
      reconfigured to be a long period FSG (LPFSG) when an amplitude mask is used.
      Experimental results show that both the short and long period FSGs can function
      as an optically tunable band-rejection filter and have different performances
      with different pump power and different configured period of the FSG. When
      configured as a SPFSG, the device can achieve a high extinction ratio (ER) of
      21.5dB and a wideband tunability of 31nm are achieved. When configured as a
      LPFSG, the device can achieve an even higher ER of 23.4dB and a wider tunable
      bandwidth of 60nm. Besides these tunable performances of the device, its full
      width at half maximum (FWHM) can also be optically tuned. The reconfigurability
      and tunability of the fiber device open up possibilities for other all-optically
      programmable and tunable fiber devices. 

PMID- 24663933
TI  - Photonic crystal-based flat lens integrated on a Bragg mirror for high-Q external
      cavity low noise laser.
AB  - We demonstrate a high reflectivity (> 99%), low-loss (< 0.1%) and aberrations
      free (2% of lambda rms phase fluctuations) concave Bragg mirror (20mm radius of
      curvature) integrating a photonic crystal with engineered spherical phase and
      amplitude transfer functions, based on a III-V semiconductors flat photonics
      technology. This mirror design is of high interest for highly coherent high power
      stable external cavity semiconductor lasers, exhibiting very low noise. We design
      the photonic crystal for operation in the pass band. The approach incorporates
      spatial, spectral (filter bandwidth= 5nm) and polarization filtering
      capabilities. Thanks to the mirror, a compact single mode TEM(00) 2mm-long air
      gap high finesse (cold cavity Q-factor 10(6) - 10(7)) stable laser cavity is
      demonstrated with a GaAs-based quantum-wells 1/2-VCSEL gain structure at 1MUm.
      Excellent laser performances are obtained in single frequency operation: low
      threshold density of 2kW/cm(2) with high differential efficiency (21%). And high
      spatial, temporal and polarization coherence: TEM(00) beam close to diffraction
      limit, linear light polarization (> 60dB), Side Mode Suppression Ratio > 46dB,
      relative intensity noise at quantum limit (< -150dB) in 1MHz-84GHz radio
      frequency range, and a theoretical linewidth fundamental limit at 10 Hz (Q-factor
      ~ 3.10(13)).

PMID- 24663934
TI  - Multi-color fluorescence imaging based on plasmonic wavelength selection and
      double illumination by white light.
AB  - We demonstrate the proof-of-concept for developing a multi-color fluorescence
      imaging system based on plasmonic wavelength selection and double illumination by
      white light source. This technique is associated with fluorescence excitation by
      transmitted light via a diffraction of propagating surface plasmons. Since double
      illumination through both sides of isosceles triangle prism in the Kretschmann
      configuration enables multiple transmission beams of different wavelengths to
      interact with the specimen, our approach can be an alternative to conventional
      fluorescence detection owing to alignment stability and functional expandability.
      After fabricating a plasmonic wavelength splitter and integrating it with
      microscopic imaging system, we successfully confirm the performance by
      visualizing in vitro neuron cells labeled with green and red fluorescence dyes.
      The suggested method has a potential that it could be combined with plasmonic
      biosensor scheme to realize a multi-functional platform which allows imaging and
      sensing of biological samples at the same time. 

PMID- 24663935
TI  - Measurements of reactive ion etching process effect using long-period fiber
      gratings.
AB  - The paper presents for the first time a study of long-period fiber gratings
      (LPFGs) applied for the measurements of reactive ion etching (RIE) process effect
      in various places of a plasma reactor. For the purposes of the experiment a
      number of highly sensitive LPFGs working at the dispersion turning point was
      fabricated using electric arc discharges. We show that the LPFGs allow for
      monitoring of the phenomena taking place in the reactor, especially those
      resulting in reduction of the LPFG diameter. Results of the measurements
      supported by simulations have shown that etching rate significantly decreases
      with elevation of the sample up to 3.6 mm over the electrode in the reactor, and
      stays constant above this height. 

PMID- 24663936
TI  - Wavefront analysis of high-efficiency, large-scale, thin transmission gratings.
AB  - Large-scale (180 * 60 * 1 mm(3)) transmission gratings with groove densities of
      1250 and 1740 lines/mm have been developed, resulting in diffraction efficiencies
      above 95%. The throughput of a folded pulse compressor with two large-scale
      transmission gratings was approximately 80% in a 20-fs Ti:sapphire chirped-pulse
      amplification (CPA) laser. The parabolic bending of the transmission grating due
      to anti-reflection (AR) coating was minimized to 2.9 lambda at 633 nm by
      improving the evaporation process. By a simple analysis, we explain why this
      level of bending does not induce a wavefront distortion through the transmission
      grating near the Littrow condition while the wavefront from a reflection grating
      is distorted to nearly twice the bending of the grating. The calculation based on
      the measured bending shows that both the group delay difference relative to the
      ideally flat grating from 750 to 850 nm and the spatial pulse front distortion
      over a 60-mm-diameter input beam are negligible, even when the dispersive beam
      covers ~140 mm on the grating. The spatial pulse front distortion measured after
      the compressor was less than the measurement limit (1.5 fs) for a 20-mm-diameter
      beam, where the beam size in the dispersive direction on the grating was 85 mm.

PMID- 24663937
TI  - Smearing model and restoration of star image under conditions of variable angular
      velocity and long exposure time.
AB  - The star tracker is one of the most promising attitude measurement devices widely
      used in spacecraft for its high accuracy. High dynamic performance is becoming
      its major restriction, and requires immediate focus and promotion. A star image
      restoration approach based on the motion degradation model of variable angular
      velocity is proposed in this paper. This method can overcome the problem of
      energy dispersion and signal to noise ratio (SNR) decrease resulting from the
      smearing of the star spot, thus preventing failed extraction and decreased star
      centroid accuracy. Simulations and laboratory experiments are conducted to verify
      the proposed methods. The restoration results demonstrate that the described
      method can recover the star spot from a long motion trail to the shape of
      Gaussian distribution under the conditions of variable angular velocity and long
      exposure time. The energy of the star spot can be concentrated to ensure high SNR
      and high position accuracy. These features are crucial to the subsequent star
      extraction and the whole performance of the star tracker. 

PMID- 24663938
TI  - Axial scanning in confocal microscopy employing adaptive lenses (CAL).
AB  - In this paper we analyze the capability of adaptive lenses to replace mechanical
      axial scanning in confocal microscopy. The adaptive approach promises to achieve
      high scan rates in a rather simple implementation. This may open up new
      applications in biomedical imaging or surface analysis in micro- and
      nanoelectronics, where currently the axial scan rates and the flexibility at the
      scan process are the limiting factors. The results show that fast and adaptive
      axial scanning is possible using electrically tunable lenses but the performance
      degrades during the scan. This is due to defocus and spherical aberrations
      introduced to the system by tuning of the adaptive lens. These detune the
      observation plane away from the best focus which strongly deteriorates the axial
      resolution by a factor of ~2.4. Introducing balancing aberrations allows
      addressing these influences. The presented approach is based on the employment of
      a second adaptive lens, located in the detection path. It enables shifting the
      observation plane back to the best focus position and thus creating axial scans
      with homogeneous axial resolution. We present simulated and experimental proof-of
      principle results. 

PMID- 24663939
TI  - Modified slanted-edge method and multidirectional modulation transfer function
      estimation.
AB  - The slanted-edge method specified in ISO Standard 12233, which measures the
      modulation transfer function (MTF) by analyzing an image of a slightly slanted
      knife-edge target, is not robust against noise because it takes the derivative of
      each data line in the edge-angle estimation. We propose here a modified method
      that estimates the edge angle by fitting a two-dimensional function to the image
      data. The method has a higher accuracy, precision, and robustness against noise
      than the ISO 12233 method and is applicable to any arbitrary pixel array,
      enabling a multidirectional MTF estimate in a single measurement of a starburst
      image. 

PMID- 24663940
TI  - Performance comparison of spectrum-narrowing equalizations with maximum
      likelihood sequence estimation and soft-decision output.
AB  - Maximum likelihood sequence estimation (MLSE) offers effective equalizations for
      bandwidth-limited optical signal on mitigation towards inter-symbol-interference
      (ISI) impairment. In this paper, we provide the first comprehensive comparisons
      and analysis of three post-compensation algorithms on the same modeling platform
      for high spectral-efficiency (SE) optical systems employing the spectral
      prefiltering. Those algorithms include 1-tap constant modulus algorithm (CMA) and
      3-tap MLSE, regular CMA and digital filter with 2-tap MLSE, and constant multi
      modulus algorithm (CMMA) with 2-tap MLSE. Furthermore, a novel and effective
      approach is proposed and verified for the generation of both hard value and soft
      value at the output of MLSE in order to be compatible with the implementation of
      soft-decision forward error correction (SD-FEC) decoding process. 

PMID- 24663941
TI  - SESAM modelocked Yb:CaGdAlO4 laser in the soliton modelocking regime with
      positive intracavity dispersion.
AB  - We demonstrate femtosecond SESAM modelocking in the near-infrared by using
      cascaded quadratic nonlinearities (phase-mismatched second-harmonic generation,
      SHG), enabling soliton modelocking in the normal dispersion regime without any
      dispersion compensating elements. To obtain large and negative self-phase
      modulation (SPM) we use an intracavity LBO crystal, whose temperature and angles
      are optimized with respect to SPM, nonlinear losses, and self-starting
      characteristics. To support femtosecond pulses, we use the very promising
      Yb:CaGdAlO(4) (CALGO) gain material, operated in a bulk configuration. The LBO
      crystal provides sufficient negative SPM to compensate for its own GDD as well as
      the positive GDD and SPM from the gain crystal. The modelocked laser produces
      pulses of 114 fs at 1050 nm, with a repetition rate of 113 MHz (average output
      power 1.1 W). We perform a detailed theoretical study of this soliton modelocking
      regime with positive GDD, which clearly indicates the important design
      constraints in an intuitive and systematic way. In particular, due to its
      importance in avoiding multi-pulsed modelocking, we examine the nonlinear loss
      associated with the cascading process carefully and show how it can be suppressed
      in practice. With this modelocking regime, it should be possible to overcome the
      limits faced by current state of the art modelocked lasers in terms of dispersion
      compensation and nonlinearity management at high powers, suppression of Q
      switching in compact GHz lasers, and enabling femtosecond soliton modelocking at
      very high repetition rates due to the high nonlinearities accessible via
      cascading combined with eliminating the need for intracavity dispersion
      compensation.

PMID- 24663942
TI  - Ultra-wide band signal generation using a coupling-tunable silicon microring
      resonator.
AB  - Ultra-wide band signal generation using a silicon microring resonator tuned to an
      NRZ-DPSK modulated optical carrier is proposed and demonstrated. The scheme is
      shown to enable the generation of UWB signals with switchable polarity and
      tunable bandwidth by simply tuning the coupling regions of the microring
      resonator. Monocycle pulses with both negative and positive polarities are
      successfully synthesized experimentally. 

PMID- 24663943
TI  - Dependent scattering in Intralipid(r) phantoms in the 600-1850 nm range.
AB  - The effect of dependent scattering on the bulk scattering properties of
      intralipid phantoms in the 600-1850 nm wavelength range has been investigated. A
      set of 57 liquid optical phantoms, covering a wide range of intralipid
      concentrations (1-100% v/v), was prepared and the bulk optical properties were
      accurately determined. The bulk scattering coefficient as a function of the
      particle density could be well described with Twersky's packing factor (R(2) >
      0.990). A general model was elaborated taking into account the wavelength
      dependency and the effect of the concentration of scattering particles (R(2) =
      0.999). Additionally, an empirical approach was followed to characterize the
      effect of dense packing of scattering particles on the anisotropy factor (R(2) =
      0.992) and the reduced scattering coefficient (R(2) = 0.999) of the phantoms. The
      derived equations can be consulted in future research for the calculation of the
      bulk scattering properties of intralipid dilutions in the 600-1850 nm range, or
      for the validation of theories that describe the effects of dependent scattering
      on the scattering properties of intralipid-like systems.

PMID- 24663944
TI  - Pulse repetition rate scaling from 5 to 100 GHz with a high-power semiconductor
      disk laser.
AB  - The high-power semiconductor laser studied here is a modelocked integrated
      external-cavity surface emitting laser (MIXSEL), which combines the gain of
      vertical-external-cavity surface-emitting lasers (VECSELs) with the saturable
      absorber of a semiconductor saturable absorber mirror (SESAM) in a single
      semiconductor layer stack. The MIXSEL concept allows for stable and self-starting
      fundamental passive modelocking in a simple straight cavity and the average power
      scaling is based on the semiconductor disk laser concept. Previously record-high
      average output power from an optically pumped MIXSEL was demonstrated, however
      the long pulse duration of 17 ps prevented higher pulse repetition rates and many
      interesting applications such as supercontinuum generation and broadband
      frequency comb generation. With a novel MIXSEL structure, the first femtosecond
      operation was then demonstrated just recently. Here we show that such a MIXSEL
      can also support pulse repetition rate scaling from ~5 GHz to >100 GHz with
      excellent beam quality and high average output power, by mechanically changing
      the cavity length of the linear straight cavity and the output coupler. Up to a
      pulse repetition rate of 15 GHz we obtained average output power >1 W and pulse
      durations <4 ps. Furthermore we have been able to demonstrate the highest pulse
      repetition rate from any fundamentally modelocked semiconductor disk laser with
      101.2 GHz at an average output power of 127 mW and a pulse duration of 570 fs.

PMID- 24663945
TI  - Compact 100Gb/s DP-QPSK integrated receiver module employing three-dimensional
      assembly technology.
AB  - We demonstrate a compact 100 Gbit/s DP-QPSK receiver module that is only 18 mm
      (W) x 16 mm (D) x 2.8 mm (H). The module size is reduced by using a ball grid
      array (BGA) package with three-dimensional assembly technology and by applying a
      heterogeneous integrated PLC. Error-free DP-QPSK signal demodulation is
      successfully demonstrated. 

PMID- 24663946
TI  - 5D-Tracking of a nanorod in a focused laser beam--a theoretical concept.
AB  - Back-focal plane (BFP) interferometry is a very fast and precise method to track
      the 3D position of a sphere within a focused laser beam using a simple quadrant
      photo diode (QPD). Here we present a concept of how to track and recover the 5D
      state of a cylindrical nanorod (3D position and 2 tilt angles) in a laser focus
      by analyzing the interference of unscattered light and light scattered at the
      cylinder. The analytical theoretical approach is based on Rayleigh-Gans
      scattering together with a local field approximation for an infinitely thin
      cylinder. The approximated BFP intensities compare well with those from a more
      rigorous numerical approach. It turns out that a displacement of the cylinder
      results in a modulation of the BFP intensity pattern, whereas a tilt of the
      cylinder results in a shift of this pattern. We therefore propose the concept of
      a local QPD in the BFP of a detection lens, where the QPD center is shifted by
      the angular coordinates of the cylinder tilt. 

PMID- 24663947
TI  - Opto-mechanical analysis of nonlinear elastomer membrane deformation under
      hydraulic pressure for variable-focus liquid-filled microlenses.
AB  - Nonlinear large deformation of a transparent elastomer membrane under hydraulic
      pressure was analyzed to investigate its optical performance for a variable-focus
      liquid-filled membrane microlens. In most membrane microlenses, actuators control
      the hydraulic pressure of optical fluid so that the elastomer membrane together
      with the internal optical fluid changes its shape, which alters the light path of
      the microlens to adapt its optical power. A fluid-structure interaction
      simulation was performed to estimate the transient behavior of the microlens
      under the operation of electroactive polymer actuators, demonstrating that the
      viscosity of the optical fluid successfully stabilizes the fluctuations within a
      fairly short period of time during dynamic operations. Axisymmetric nonlinear
      plate theory was used to calculate the deformation profile of the membrane under
      hydrostatic pressure, with which optical characteristics of the membrane
      microlens were estimated. The effects of gravitation and viscoelastic behavior of
      the elastomer membrane on the optical performance of the membrane microlens were
      also evaluated with finite element analysis. 

PMID- 24663948
TI  - Pulse bundles and passive harmonic mode-locked pulses in Tm-doped fiber laser
      based on nonlinear polarization rotation.
AB  - We demonstrate the nanosecond-level pulses in Tm-doped fiber laser generated by
      passively harmonic mode-locking. Nonlinear polarization rotation performed by two
      polarization controllers (PCs) is employed to induce the self-starting harmonic
      mode-locking. The fundamental repetition rate of the laser is 448.8 kHz, decided
      by the length of the cavity. Bundles of pulses with up to 17 uniform subpulses
      are generated due to the split of pulse when the pump power increases and the PCs
      are adjusted. Continuous harmonic mode-locked pulse trains are obtained with 1st
      to 6th and even more than 15th order when the positions of the PCs are properly
      fixed and the pump power is scaled up. The widths of all the uniform individual
      pulses are mostly 3-5 ns, and pulse with width of 304 ns at fundamental
      repetition rate can also be generated by adjusting the PCs. Hysteresis phenomenon
      of the passively harmonic mode-locked pulses' repetition frequency versus pump
      power is observed. The rather wide 3dB spectral bandwidth of the pulse train (25
      nm) indicates that they may resemble noise-like pulses. 

PMID- 24663949
TI  - Non-uniform lateral current distribution in quantum cascade lasers.
AB  - Non-uniform lateral current distribution in quantum cascade (QC) lasers is
      investigated, as a result of stimulated-optical-emission-assisted electron
      transport, the rate of which depends on the local photon density and is
      comparable to the longitudinal optical (LO) phonon scattering rate. A microscopic
      model based on rate equations is built to study the self-consistent process of
      interaction between local electrons and photons in QC lasers. The non-uniform
      distribution of lateral current and the corresponding spatial hole burning are
      simulated from this model. Moreover, multi-transverse-mode operation in QC lasers
      is also investigated. 

PMID- 24663950
TI  - A femtosecond pulse erbium fiber laser incorporating a saturable absorber based
      on bulk-structured Bi2Te3 topological insulator.
AB  - We experimentally demonstrate the use of a bulk-structured Bi(2)Te(3) topological
      insulator (TI) as an ultrafast mode-locker to generate femtosecond pulses from an
      all-fiberized cavity. Using a saturable absorber based on a mechanically
      exfoliated layer about 15 MUm thick deposited onto a side-polished fiber, we show
      that stable soliton pulses with a temporal width of ~600 fs can readily be
      produced at 1547 nm from an erbium fiber ring cavity. Unlike previous TI-based
      mode-locked laser demonstrations, in which high-quality nanosheet-based TIs were
      used for saturable absorption, we chose to use a bulk-structured Bi(2)Te(3) layer
      because it is easy to fabricate. We found that the bulk-structured Bi(2)Te(3)
      layer can readily provide sufficient nonlinear saturable absorption for
      femtosecond mode-locking even if its modulation depth of ~15.7% is much lower
      than previously demonstrated nanosheet-structured TI-based saturable absorbers.
      This experimental demonstration indicates that high-crystalline-quality atomic
      layered films of TI, which demand complicated and expensive material processing
      facilities, are not essential for ultrafast laser mode-locking applications.

PMID- 24663951
TI  - Compact surface plasmon resonance imaging sensing system based on general
      optoelectronic components.
AB  - We present a simple surface plasmon resonance imaging (SPRi) sensing system based
      on some common optoelectronic devices in this paper. Using an optical fiber based
      SPR sensor as sensing element in our system, the SPRi system is dramatically
      compact. A small universal LED is used as the light source. The light intensity
      is record as images that can be captured by a simple web camera. A Microsoft
      Visual C++6.0 based Windows software program is written to process the image data
      which contain SPRi information. Experimental results show that the relationship
      between the relative intensity and RI is a linear relation in a RI range from
      1.3396 to 1.3645. Using this SPRi device, we measure the specific binding between
      the Con A and RNase B, which demonstrates its capability for biomedical selective
      affinity monitoring. The proposed SPRi sensing system also has the capacity for
      biochemical multiple channel measurement with further investigation. 

PMID- 24663952
TI  - Optical correlation algorithm for reconstructing phase skeleton of complex
      optical fields for solving the phase problem.
AB  - We propose an optical correlation algorithm illustrating a new general method for
      reconstructing the phase skeleton of complex optical fields from the measured two
      dimensional intensity distribution. The core of the algorithm consists in
      locating the saddle points of the intensity distribution and connecting such
      points into nets by the lines of intensity gradient that are closely associated
      with the equi-phase lines of the field. This algorithm provides a new partial
      solution to the inverse problem in optics commonly referred to as the phase
      problem. 

PMID- 24663953
TI  - High flux coherent super-continuum soft X-ray source driven by a single-stage,
      10mJ, Ti:sapphire amplifier-pumped OPA.
AB  - We demonstrate the highest flux tabletop source of coherent soft X-rays to date,
      driven by a single-stage 10 mJ Ti:sapphire regenerative amplifier at 1 kHz. We
      first down-convert the laser to 1.3 um using a parametric amplifier, before up
      converting it to soft X-rays using high harmonic generation in a high-pressure,
      phase matched, hollow waveguide geometry. The resulting optimally phase matched
      broadband spectrum extends to 200 eV, with a soft X-ray photon flux of > 10(6)
      photons/pulse/1% bandwidth at 1 kHz, corresponding to > 10(9) photons/s/1%
      bandwidth, or approximately a three order-of-magnitude increase compared with
      past work. Finally, using this broad bandwidth X-ray source, we demonstrate X-ray
      absorption spectroscopy of multiple elements and transitions in molecules in a
      single spectrum, with a spectral resolution of 0.25 eV, and with the ability to
      resolve the near edge fine structure.

PMID- 24663954
TI  - Cytokines, Chemokines, and Growth Factors in Banked Human Donor Milk for Preterm
      Infants.
AB  - BACKGROUND: There has been a recent increase in availability of banked donor milk
      for feeding of preterm infants. This milk is pooled from donations to milk banks
      from carefully screened lactating women. The milk is then pasteurized by the
      Holder method to remove all microbes. The processed milk is frozen, banked, and
      sold to neonatal intensive care units (NICUs). The nutrient bioavailability of
      banked donor milk has been described, but little is known about preservation of
      immune components such as cytokines, chemokines, and growth factors (CCGF).
      OBJECTIVE: The objective was to compare CCGF in banked donor milk with mother's
      own milk (MOM). METHODS: Aliquots (0.5 mL) were collected daily from MOM pumped
      by 45 mothers of NICU-admitted infants weighing < 1500 grams at birth. All daily
      aliquots of each mother's milk were pooled each week during 6 weeks of an
      infant's NICU stay or for as long as the mother provided MOM. The weekly pooled
      milk was measured for a panel of CCGF through multiplexing using magnetic beads
      and a MAGPIX instrument. Banked donor milk samples (n = 25) were handled and
      measured in the same way as MOM. RESULTS: Multiplex analysis revealed that there
      were levels of CCGF in banked donor milk samples comparable to values obtained
      from MOM after 6 weeks of lactation. CONCLUSION: These data suggest that many
      important CCGF are not destroyed by Holder pasteurization.

PMID- 24663955
TI  - A functional microengineered model of the human splenon-on-a-chip.
AB  - The spleen is a secondary lymphoid organ specialized in the filtration of
      senescent, damaged, or infected red blood cells. This unique filtering capacity
      is largely due to blood microcirculation through filtration beds of the splenic
      red pulp in an open-slow microcirculation compartment where the hematocrit
      increases, facilitating the recognition and destruction of unhealthy red blood
      cells by specialized macrophages. Moreover, in sinusal spleens such as those of
      humans, blood in the open-slow microcirculation compartment has a unidirectional
      passage through interendothelial slits before reaching the venous system. This
      further physical constraint represents a second stringent test for erythrocytes
      ensuring elimination of those cells lacking deformability. With the aim of
      replicating the filtering function of the spleen on a chip, we have designed a
      novel microengineered device mimicking the hydrodynamic forces and the physical
      properties of the splenon, the minimal functional unit of the red pulp able to
      maintain filtering functions. In this biomimetic platform, we have evaluated the
      mechanical and physiological responses of the splenon using human red blood cells
      and malaria-infected cells. This novel device should facilitate future functional
      studies of the spleen in relation to malaria and other hematological disorders. 

PMID- 24663956
TI  - ST2 deficiency does not impair type 2 immune responses during chronic filarial
      infection but leads to an increased microfilaremia due to an impaired splenic
      microfilarial clearance.
AB  - BACKGROUND: Interactions of the Th2 cytokine IL-33 with its receptor ST2 lead to
      amplified Type 2 immune responses. As Type 2 immune responses are known to
      mediate protection against helminth infections we hypothesized that the lack of
      ST2 would lead to an increased susceptibility to filarial infections.
      METHODOLOGY/PRINCIPAL FINDING: ST2 deficient and immunocompetent BALB/c mice were
      infected with the filarial nematode Litomosoides sigmodontis. At different time
      points after infection mice were analyzed for worm burden and their immune
      responses were examined within the thoracic cavity, the site of infection, and
      systemically using spleen cells and plasma. Absence of ST2 led to significantly
      increased levels of peripheral blood microfilariae, the filarial progeny, whereas
      L. sigmodontis adult worm burden was not affected. Development of local and
      systemic Type 2 immune responses were not impaired in ST2 deficient mice after
      the onset of microfilaremia, but L. sigmodontis infected ST2-ko mice had
      significantly reduced total numbers of cells within the thoracic cavity and
      spleen compared to infected immunocompetent controls. Pronounced microfilaremia
      in ST2-ko mice did not result from an increased microfilariae release by adult
      female worms, but an impaired splenic clearance of microfilariae.
      CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the absence of ST2 does not
      impair the establishment of adult L. sigmodontis worms, but is important for the
      splenic clearance of microfilariae from peripheral blood. Thus, ST2 interactions
      may be important for therapies that intend to block the transmission of filarial
      disease.

PMID- 24663958
TI  - Body image and self-esteem in lower-limb amputees.
AB  - BACKGROUND: Limb amputation is often an inevitable procedure in the advanced
      condition of various diseases and poses a dramatic impact on a patient's life.
      The aim of the present study is to analyze the impact of lower-limb amputations
      on aesthetic factors such as body image and self-esteem as well as quality of
      life (QoL). METHODS: 298 patients (149 uni- or bilateral lower-limb amputees and
      149 controls) were included in this cross-sectional study in three centers.
      Demographic data was collected and patients received a 118-item questionnaire
      including the Multidimensional Body-Self Relations Questionnaire (MBSRQ), the
      Rosenberg Self-esteem (RSE) scale and the SF-36 Health Survey (QoL). ANOVA and
      student's t-test were used for statistical analysis. RESULTS: Unilateral lower
      limb amputees showed a significant lower MBSRQ score of 3.07+/-0.54 compared with
      3.41+/-0.34 in controls (p<0.001) and a lower score in the RSE compared to
      controls (21.63+/-4.72 vs. 21.46+/-5.86). However, differences were not
      statistically significant (p = 0.36). Patients with phantom pain sensation had a
      significantly reduced RSE (p = 0.01). The SF-36 health survey was significantly
      lower in patients with lower-limb amputation compared to controls (42.17+/-14.47
      vs. 64.05+/-12.39) (p<0.001). CONCLUSION: This study showed that lower-limb
      amputations significantly influence patients' body image and QoL. Self-esteem
      seems to be an independent aspect, which is not affected by lower-limb
      amputation. However, self-esteem is influenced significantly by phantom pain
      sensation.

PMID- 24663957
TI  - cuTauLeaping: a GPU-powered tau-leaping stochastic simulator for massive parallel
      analyses of biological systems.
AB  - Tau-leaping is a stochastic simulation algorithm that efficiently reconstructs
      the temporal evolution of biological systems, modeled according to the stochastic
      formulation of chemical kinetics. The analysis of dynamical properties of these
      systems in physiological and perturbed conditions usually requires the execution
      of a large number of simulations, leading to high computational costs. Since each
      simulation can be executed independently from the others, a massive
      parallelization of tau-leaping can bring to relevant reductions of the overall
      running time. The emerging field of General Purpose Graphic Processing Units
      (GPGPU) provides power-efficient high-performance computing at a relatively low
      cost. In this work we introduce cuTauLeaping, a stochastic simulator of
      biological systems that makes use of GPGPU computing to execute multiple parallel
      tau-leaping simulations, by fully exploiting the Nvidia's Fermi GPU architecture.
      We show how a considerable computational speedup is achieved on GPU by
      partitioning the execution of tau-leaping into multiple separated phases, and we
      describe how to avoid some implementation pitfalls related to the scarcity of
      memory resources on the GPU streaming multiprocessors. Our results show that
      cuTauLeaping largely outperforms the CPU-based tau-leaping implementation when
      the number of parallel simulations increases, with a break-even directly
      depending on the size of the biological system and on the complexity of its
      emergent dynamics. In particular, cuTauLeaping is exploited to investigate the
      probability distribution of bistable states in the Schlogl model, and to carry
      out a bidimensional parameter sweep analysis to study the oscillatory regimes in
      the Ras/cAMP/PKA pathway in S. cerevisiae. 

PMID- 24663960
TI  - Summaries for patients. Screening for cognitive impairment in older adults: U.S.
      Preventive Services Task Force recommendation statement.

PMID- 24663959
TI  - uPARAP function in cutaneous wound repair.
AB  - Optimal skin wound healing relies on tight balance between collagen synthesis and
      degradation in new tissue formation and remodeling phases. The endocytic receptor
      uPARAP regulates collagen uptake and intracellular degradation. In this study we
      examined cutaneous wound repair response of uPARAP null (uPARAP-/-) mice. Full
      thickness wounds were created on dorsal surface of uPARAP-/- or their wildtype
      littermates. Wound healing evaluation was done by macroscopic observation,
      histology, gene transcription and biochemical analysis at specific intervals. We
      found that absence of uPARAP delayed re-epithelialization during wound closure,
      and altered stiffness of the scar tissue. Despite the absence of the uPARAP
      mediated intracellular pathway for collagen degradation, there was no difference
      in total collagen content of the wounds in uPARAP-/- compared to wildtype mice.
      This suggests in the absence of uPARAP, a compensatory feedback mechanism
      functions to keep net collagen in balance. 

PMID- 24663964
TI  - Diminished metal accumulation in riverine fishes exposed to acid mine drainage
      over five decades.
AB  - Bony bream (Nematalosa erebi) and black catfish (Neosilurus ater) were sampled
      from the fresh surface waters of the Finniss River in tropical northern
      Australia, along a metal pollution gradient draining the Rum Jungle
      copper/uranium mine, a contaminant source for over five decades. Paradoxically,
      populations of both fish species exposed to the highest concentrations of mine
      related metals (cobalt, copper, lead, manganese, nickel, uranium and zinc) in
      surface water and sediment had the lowest tissue (bone, liver and muscle)
      concentrations of these metals. The degree of reduction in tissue concentrations
      of exposed populations was also specific to each metal and inversely related to
      its degree of environmental increase above background. Several explanations for
      diminished metal bioaccumulation in fishes from the contaminated region were
      evaluated. Geochemical speciation modeling of metal bioavailability in surface
      water showed no differences between the contaminated region and the control
      sites. Also, the macro-nutrient (calcium, magnesium and sodium) water
      concentrations, that may competitively inhibit metal uptake, were not elevated
      with trace metal contamination. Reduced exposure to contaminants due to avoidance
      behavior was unlikely due to the absence of refugial water bodies with the
      requisite metal concentrations lower than the control sites and very reduced
      connectivity at time of sampling. The most plausible interpretation of these
      results is that populations of both fish species have modified kinetics within
      their metal bioaccumulation physiology, via adaptation or tolerance responses, to
      reduce their body burdens of metals. This hypothesis is consistent with (i)
      reduced tissue concentrations of calcium, magnesium and sodium (macro-nutrients),
      in exposed populations of both species, (ii) experimental findings for other fish
      species from the Finniss River and other contaminated regions, and (iii) the
      number of generations exposed to likely selection pressure over 50 years. 

PMID- 24663961
TI  - Major improvements in the quality of malaria case-management under the "test and
      treat" policy in Kenya.
AB  - BACKGROUND: Monitoring implementation of the "test and treat" case-management
      policy for malaria is an important component of all malaria control programmes in
      Africa. Unfortunately, routine information systems are commonly deficient to
      provide necessary information. Using health facility surveys we monitored health
      systems readiness and malaria case-management practices prior to and following
      implementation of the 2010 "test and treat" policy in Kenya. METHODS/FINDINGS:
      Between 2010 and 2013 six national, cross-sectional, health facility surveys were
      undertaken. The number of facilities assessed ranged between 172 and 176, health
      workers interviewed between 216 and 237 and outpatient consultations for febrile
      patients evaluated between 1,208 and 2,408 across six surveys. Comparing baseline
      and the last survey results, all readiness indicators showed significant
      (p<0.005) improvements: availability of parasitological diagnosis (55.2% to
      90.7%); RDT availability (7.5% to 69.8%); total artemether-lumefantrine (AL)
      stock-out (27.2% to 7.0%); stock-out of one or more AL packs (59.5% to 21.6%);
      training coverage (0 to 50.2%); guidelines access (0 to 58.1%) and supervision
      (17.9% to 30.8%). Testing increased by 34.0% (23.9% to 57.9%; p<0.001) while
      testing and treatment according to test result increased by 34.2% (15.7% to
      49.9%; p<0.001). Treatment adherence for test positive patients improved from
      83.3% to 90.3% (p = 0.138) and for test negative patients from 47.9% to 83.4%
      (p<0.001). Significant testing and treatment improvements were observed in
      children and adults. There was no difference in practices with respect to the
      type and result of malaria test (RDT vs microscopy). Of eight dosing, dispensing
      and counseling tasks, improvements were observed for four tasks. Overall AL use
      for febrile patients decreased from 63.5% to 35.6% (p<0.001). CONCLUSIONS: Major
      improvements in the implementation of "test and treat" policy were observed in
      Kenya. Some gaps towards universal targets still remained. Other countries facing
      similar needs and challenges may consider health facility surveys to monitor
      malaria case-management.

PMID- 24663965
TI  - The use of partial nephrectomy: results from a contemporary national prospective
      multicenter study.
AB  - PURPOSE: Despite benefits in functional renal outcome and favorable oncological
      efficacy, previous studies show marked underuse of partial nephrectomy (PN). We
      investigated national utilization of partial and radical nephrectomy (RN) using a
      contemporary, prospective population-based cohort. METHODS: Between June and
      December 2010, 1,237 patients were treated by PN or RN for renal cell carcinoma
      in 56 French centers. Data were prospectively collected, and statistical analyses
      were performed. RESULTS: Overall, 667 (53.9 %) and 570 patients (46.1 %)
      underwent RN and PN, respectively. In case of PN, surgical approach was an open
      PN in 63.3 % of cases, a laparoscopic PN in 21.0 % of cases and a robot-assisted
      PN in 15.7 % of cases. PN was used in T1a, T1b, T2 and T3 tumors in 395 (76.7 %),
      131 (38.2 %), 29 (14.7 %) and 7 (4.6 %), respectively. Median ischemia time was
      16 min [0-60], and mean blood loss was 280.4 ml (+/-339.9). Tumor characteristics
      and operative features were significantly different according to the surgical
      approach. Warm ischemia time was significantly higher in case of laparoscopic or
      robot-assisted procedure (p < 0.001). There was no statistical significant
      difference in blood loss and transfusion rate according to surgical approach.
      Postoperative medical and surgical complications occurred in 8.2 and 10.0 % of
      PN, respectively, with no significant difference according to surgical approach.
      CONCLUSIONS: Partial nephrectomy for renal cell carcinoma is commonly used in
      this French centers sample. Mini-invasive approaches represent also a significant
      part of all partial nephrectomies with no difference in terms of complication
      rates.

PMID- 24663966
TI  - Development and validation of an HPLC method for determination of Amikacin in
      water samples by solid phase extraction and pre-column derivatization.
AB  - This work presents a rapid and sensitive high performance liquid chromatography
      method for the determination of amikacin in water samples with solid phase
      extraction and pre-column derivatization. Amikacin residue was extracted from
      water samples with solid phase extraction cartridge. Then the extraction solution
      was derivatized with 4-chloro-3,5-dinitrobenzotrifluoride in the presence of
      triethylamine at 70 degrees C in 20 min. The amikacin derivative was separated on
      a C18 column and detected by application of UV detection at 238 nm. The limit of
      detection is 0.2 MUg/L with a signal-to-noise ratio of 3 and linearity is
      established over the concentration range from 0 to 500.0 MUg/L. Recoveries of the
      amikacin in three types of water samples are from 87.5 % to 99.6 % and RSDs are
      2.1 %-4.5 %. This method can be used for the quantification of amikacin residues
      in water samples.

PMID- 24663968
TI  - On-the-field performance of quintuple-play long-reach OFDM-based WDM-PON optical
      access networks.
AB  - In this paper the on-the-field performance of a WDM-PON optical access providing
      quintuple-play services using orthogonal frequency division multiplexing (OFDM)
      modulation is evaluated in a real fiber-to-the-home (FTTH) network deployed by
      Towercom operator in Bratislava (Slovakia). A bundle of quintuple-play services
      comprising full-standard OFDM-based signals (LTE, WiMAX, UWB and DVB-T) and an ad
      hoc OFDM-GbE signal is transmitted in coexistence per single user. Both
      downstream and upstream transmission performances are evaluated in different on
      the-field long-reach optical link distance configurations. Four wavelength multi
      user transmission of quintuple-play OFDM services is demonstrated exceeding 60.8
      km reach in standard single mode fiber.

PMID- 24663969
TI  - Tiled large-screen three-dimensional display consisting of frameless multi-view
      display modules.
AB  - To realize large-screen three-dimensional (3D) displays, frameless multi-view
      display modules are arranged two-dimensionally. This paper proposes a multi-view
      display module in which a multi-view flat-panel display is projected onto a
      screen of the module to provide a frameless screen. The display module consists
      of a multi-view flat-panel display, an imaging lens, an aperture, a screen lens,
      and a vertical diffuser. Prototype display modules were constructed having a
      screen size of 27.3 in., a 3D resolution of 320 * 200, and 144 viewpoints. Four
      modules were tiled vertically to provide a screen size of 62.4 in. Distortions in
      the screen imaging and viewpoint generation were corrected. 

PMID- 24663967
TI  - Action experience, more than observation, influences mu rhythm desynchronization.
AB  - Since the discovery of mirror neurons in premotor and parietal areas of the
      macaque monkey, the idea that action and perception may share the same neural
      code has been of central interest in social, developmental, and cognitive
      neurosciences. A fundamental question concerns how a putative human mirror neuron
      system may be tuned to the motor experiences of the individual. The current study
      tested the hypothesis that prior motor experience modulated the sensorimotor mu
      and beta rhythms. Specifically, we hypothesized that these sensorimotor rhythms
      would be more desynchronized after active motor experience compared to passive
      observation experience. To test our hypothesis, we collected EEG from adult
      participants during the observation of a relatively novel action: an experimenter
      used a claw-like tool to pick up a toy. Prior to EEG collection, we trained one
      group of adults to perform this action with the tool (performers). A second group
      comprised trained video coders, who only had experience observing the action
      (observers). Both the performers and the observers had no prior motor and visual
      experience with the action. A third group of novices was also tested. Performers
      exhibited the greatest mu rhythm desynchronization in the 8-13 Hz band,
      particularly in the right hemisphere compared to observers and novices. This
      study is the first to contrast active tool-use experience and observation
      experience in the mu rhythm and to show modulation with relatively shorter
      amounts of experience than prior mirror neuron expertise studies. These findings
      are discussed with respect to its broader implication as a neural signature for a
      mechanism of early social learning. 

PMID- 24663970
TI  - Using pulse transit delay in Z-scan to discriminate between excited-state
      absorption and other nonlinear processes in ZnO nanocones.
AB  - We report a new approach that uses the single beam Z-scan technique, to
      discriminate between excited state absorption (ESA) and two and three photon
      nonlinear absorption. By measuring the apparent delay or advance of the pulse in
      reaching the detector, the nonlinear absorption can be unambiguously identified
      as either instantaneous or transient. The simple method does not require a large
      range of input fluences or sophisticated pulse-probe experimental apparatus. The
      technique is easily extended to any absorption process dependent on pulse width
      and to nonlinear refraction measurements. We demonstrate in particular, that the
      large nonlinear absorption in ZnO nanocones when exposed to nanosecond 532 nm
      pulses, is due mostly to ESA, not pure two-photon absorption. 

PMID- 24663971
TI  - Low-threshold lasing in photonic-crystal heterostructures.
AB  - We study a photonic crystal (PhC) heterostructure cavity consisting of gain
      medium in a three-dimensional (3D) PhC sandwiched between two identical passive
      multilayers. For this structure, based on Korringa-Kohn-Rostoker method, we
      observe a decrease in the lasing threshold of two orders of magnitude, as
      compared with a stand-alone 3D PhC. We attribute this remarkable decrease in
      threshold gain to the overlap of the defect cavity mode with the reduced group
      velocity region of the PhC's dispersion, and the associated enhancement in the
      distributed feedback from the ordered layers of the PhC. The obtained results
      show the potency for designing PhC-based, compact on-chip lasers with ultra-low
      thresholds. 

PMID- 24663972
TI  - Short pulse carrier-envelope phase absolute single-shot measurement by
      photoionization of gases with a guided laser beam.
AB  - We present an all optical approach to measure the value of the carrier-envelope
      phase (CEP) of a short intense laser pulse. This method relies on photo
      ionization of gases with a guided laser beam. This approach that provides the
      absolute value of the CEP, is compatible with single shot characterization, is
      scalable in wavelength, does not suffer from bandwidth limitation and is largely
      intensity independent. It has also the potential to provide a full
      characterization of the pulse profile via high order autocorrelation on a single
      shot basis. 

PMID- 24663973
TI  - Tracing photon transmission in dye-doped DNA-CTMA optical nanofibers.
AB  - We experimentally demonstrate the novel phenomena of photoluminescence (PL) and
      fluorescence resonance energy transfer (FRET) assisted three-color PL separating
      in DNA optical nanofibers consisting of the stretched and connected DNA
      cetyltrimethyl ammonium wires. The PL experiments are performed to comparatively
      trace photon transmission between single dye-doped DNA-CTMA optical nanofiber and
      PMMA optical nanofiber. A cascade FRET including DNA minor groove binder and DNA
      intercalators is used to further trace photon transmission inside DNA-CTMA wire.
      These experimental results will help to intrigue the new applications of DNA-CTMA
      as molecular waveguide in optobioelectronics area.

PMID- 24663974
TI  - Efficient and broadband parametric wavelength conversion in a vertically etched
      silicon grating without dispersion engineering.
AB  - An efficient and broadband parametric wavelength converter is proposed in the
      silicon-on-insulator (SOI) waveguide without dispersion engineering. The vertical
      grating is utilized to achieve the quasi-phase-matching (QPM) of four-wave mixing
      (FWM). By alternating the phase-mismatch between two values with opposite signs,
      the parametric attenuation is suppressed. The conversion efficiency at the
      designated signal wavelength is significantly improved, and the 3-dB conversion
      bandwidth is also extended effectively. It is demonstrated that the conversion
      bandwidth is insensitive to both the propagation length and the grating width,
      which alleviates the tradeoff between the conversion bandwidth and the peak
      conversion efficiency. For a continuous-wave (CW) pump at 1550 nm, a conversion
      bandwidth of 331 nm and a peak efficiency of -12.8 dB can be realized in a 1.5-cm
      long grating with serious phase-mismatch. 

PMID- 24663975
TI  - FDTD simulation of transmittance characteristics of one-dimensional conducting
      electrodes.
AB  - We investigated transparent conducting electrodes consisting of periodic one
      dimensional Ag or Al grids with widths from 25 nm to 5 MUm via the finite
      difference time-domain method. To retain high transmittance, two grid
      configurations with opening ratios of 90% and 95% were simulated. Polarization
      dependent characteristics of the transmission spectra revealed that the overall
      transmittance of micron-scale grid electrodes may be estimated by the sum of
      light power passing through the uncovered area and the light power penetrating
      the covered metal layer. However, several dominant physical phenomena
      significantly affect the transmission spectra of the nanoscale grids: Rayleigh
      anomaly, transmission decay in TE polarized mode, and localized surface plasmon
      resonance. We conclude that, for applications of transparent electrodes, the
      critical feature sizes of conducting 1D grids should not be less than the
      wavelength scale in order to maintain uniform and predictable transmission
      spectra and low electrical resistivity.

PMID- 24663976
TI  - The application of cost-effective lasers in coherent UDWDM-OFDM-PON aided by
      effective phase noise suppression methods.
AB  - Digital coherent passive optical network (PON), especially the coherent
      orthogonal frequency division multiplexing PON (OFDM-PON), is a strong candidate
      for the 2nd-stage-next-generation PON (NG-PON2). As is known, OFDM is very
      sensitive to the laser phase noise which severely limits the application of the
      cost-effective distributed feedback (DFB) lasers and more energy-efficient
      vertical cavity surface emitting lasers (VCSEL) in the coherent OFDM-PON. The
      current long-reach coherent OFDM-PON experiments always choose the expensive
      external cavity laser (ECL) as the optical source for its narrow linewidth
      (usually<100 KHz). To solve this problem, we introduce the orthogonal basis
      expansion based (OBE) phase noise suppression method to the coherent OFDM-PON and
      study the possibility of the application of the DFB lasers and VCSEL in coherent
      OFDM-PON. A typical long-reach coherent ultra dense wavelength division
      multiplexing (UDWDM) OFDM-PON has been set up. The numerical results prove that
      the OBE method can stand severe phase noise of the lasers in this architecture
      and the DFB lasers as well as VCSEL can be used in coherent OFDM-PON. In this
      paper, we have also analyzed the performance of the RF-pilot-aided (RFP) phase
      noise suppression method in coherent OFDM-PON.

PMID- 24663977
TI  - Tunable reflector with active magnetic metamaterials.
AB  - We placed active magnetic metamaterials on metallic surface to implement a
      tunable reflector with excellent agile performance. By incorporating active
      elements into the unit cells of the magnetic metamaterial, this active magnetic
      metamaterial can be tuned to switch function of the reflector among a perfect
      absorber, a perfect reflector and a gain reflector. This brings about DC control
      lines to electrically tune the active magnetic metamaterial with positive loss,
      zero loss and even negative loss. The design, analytical and numerical simulation
      methods, and experimental results of the tunable reflector are presented. 

PMID- 24663978
TI  - Pulse compression in adiabatically tapered silicon photonic wires.
AB  - We present a comprehensive analysis of pulse compression in adiabatically tapered
      silicon photonic wire waveguides (Si-PhWWGs), both at telecom (lambda ~ 1.55 MUm)
      and mid-IR (lambda ? 2.1 MUm) wavelengths. Our theoretical and computational
      study is based on a rigorous model that describes the coupled dynamics of the
      optical field and photogenerated free carriers, as well as the influence of the
      physical and geometrical parameters of the Si-PhWWGs on these dynamics. We
      consider both the soliton and non-soliton pulse propagation regimes, rendering
      the conclusions of this study relevant to a broad range of experimental settings
      and practical applications. In particular, we show that by engineering the linear
      and nonlinear optical properties of Si-PhWWGs through adiabatically varying their
      width, one can achieve more than 10* pulse compression in millimeter-long
      waveguides. The inter-dependence between the pulse characteristics and
      compression efficiency is also discussed.

PMID- 24663979
TI  - Tunable optical and magneto-optical properties of ferrofluid in the terahertz
      regime.
AB  - The dielectric property and magneto-optical effects of ferrofluids have been
      investigated in the terahertz (THz) regime by using THz time-domain spectroscopy.
      The experiment results show that the refractive index and absorption coefficient
      of ferrofluid for THz waves rise up with the increase of nanoparticle
      concentration in the ferrofluid. Moreover, two different THz magneto-optical
      effects have been found with different external magnetic fields, of which
      mechanisms have been theoretically explained well by microscopic structure
      induced refractive index change in the magnetization process and the transverse
      magneto-optical effect after the saturation magnetization, respectively. This
      work suggests that ferrofluid is a promising magneto-optical material in the THz
      regime which has widely potential applications in THz functional devices for THz
      sensing, modulation, phase retardation, and polarization control.

PMID- 24663980
TI  - Strain effect on the optical polarization properties of c-plane Al0.26Ga0.74N/GaN
      superlattices.
AB  - A new approach to realize ultraviolet (UV) light emitting diodes (LEDs) is using
      AlN/GaN or AlxGa1-xN/GaN SL structure as active layers. Effect of a uniaxial
      strain on the degree of polarization (DOP) of Al0.26Ga0.74N/GaN superlattices
      (SLs) grown on c-plane sapphire substrates has been investigated. Compared with
      AlN/AlxGa1-xN quantum wells, the DOP of the light emission from Al0.26Ga0.74N/GaN
      SLs shows an opposite variation tendency with in-plane strain and quantum
      confinement. The results would be helpful to the structural design of c-plane
      deep-UV and UVA LEDs to enhance surface emission.

PMID- 24663981
TI  - Compression of ultra-long microwave pulses using programmable microwave photonic
      phase filtering with > 100 complex-coefficient taps.
AB  - Microwave photonic filters with arbitrary phase response can be achieved by
      merging high-repetition-rate electro-optic frequency comb technology with line-by
      line pulse shaping. When arranged in an interferometric configuration, the filter
      features a number of programmable complex-coefficient taps equal to the number of
      available comb lines. In this work, we use an ultrabroadband comb generator
      resulting in a microwave photonic phase filter with >100 complex-coefficient
      taps. We demonstrate the potential of this filter by performing programmable
      chirp control of ultrawideband waveforms that extend over long (>10 ns) temporal
      apertures. This work opens new possibilities for compensating realistic linear
      distortion impairments on ultrabroadband wireless signals spanning over dozens of
      nanosecond temporal apertures.

PMID- 24663982
TI  - Record-high and robust 17.125 Gb/s gross-rate over 25 km SSMF transmissions of
      real-time dual-band optical OFDM signals directly modulated by 1 GHz RSOAs.
AB  - Aggregated 17.125 Gb/s real-time end-to-end dual-band optical OFDM (OOFDM)
      transmissions over 25 km SSMF IMDD systems with 7 dB receiver sensitivity
      improvements are experimentally demonstrated, for the first time, by utilizing
      low-cost transceiver components such as directly modulated 1GHz RSOAs and
      DACs/ADCs operating at sampling speeds as low as 4GS/s. The demonstrated OOFDM
      transceivers have both strong adaptability and sufficiently large passband
      carrier frequency tunability, which enable full use of highly dynamic spectral
      characteristics of the transmission systems. This results in the achievements of
      not only excellent performance robustness to variations in system operating
      conditions but also significantly relaxed requirements on RSOA small-signal
      modulation bandwidth. It is shown that the aforementioned transmission capacity
      only varies by <23% over a RSOA-injected optical power variation range as large
      as 20dB, and that the 1 GHz RSOAs can support successful transmissions of
      adaptively modulated OOFDM signals having bandwidths of 8.5 GHz. By taking into
      account the adopted 25% cyclic prefix and a typical 7.3% FEC overhead, the
      demonstrated real-time OOFDM transmission systems are capable of conveying 11.6
      Gb/s user data.

PMID- 24663984
TI  - Probing rotational wave-packet dynamics with the structural minimum in high-order
      harmonic spectra.
AB  - We investigate the alignment-dependent high-order harmonic spectrum generated
      from nonadiabatically aligned molecules around the first half rotational revival.
      It is found that the evolution of the molecular alignment is encoded in the
      structural minima. To reveal the relation between the molecular alignment and the
      structural minimum in the high-order harmonic spectrum, we perform an analysis
      based on the two-center interference model. Our analysis shows that the
      structural minimum position depends linearly on the inverse of the alignment
      parameter <cos<sup>2</sup>theta>. This linear relation indicates the possibility
      of probing the rotational wave-packet dynamics by measuring the spectral minima. 

PMID- 24663983
TI  - Correction of optical absorption and scattering variations in Laser Speckle
      Rheology measurements.
AB  - Laser Speckle Rheology (LSR) is an optical technique to evaluate the viscoelastic
      properties by analyzing the temporal fluctuations of backscattered speckle
      patterns. Variations of optical absorption and reduced scattering coefficients
      further modulate speckle fluctuations, posing a critical challenge for
      quantitative evaluation of viscoelasticity. We compare and contrast two different
      approaches applicable for correcting and isolating the collective influence of
      absorption and scattering, to accurately measure mechanical properties. Our
      results indicate that the numerical approach of Monte-Carlo ray tracing (MCRT)
      reliably compensates for any arbitrary optical variations. When scattering
      dominates absorption, yet absorption is non-negligible, diffusing wave
      spectroscopy (DWS) formalisms perform similar to MCRT, superseding other
      analytical compensation approaches such as Telegrapher equation. The
      computational convenience of DWS greatly simplifies the extraction of
      viscoelastic properties from LSR measurements in a number of chemical,
      industrial, and biomedical applications.

PMID- 24663985
TI  - High-efficiency 20 W yellow VECSEL.
AB  - A high-efficiency optically pumped vertical-external-cavity surface-emitting
      laser emitting 20 W at a wavelength around 588 nm is demonstrated. The
      semiconductor gain chip emitted at a fundamental wavelength around 1170-1180 nm
      and the laser employed a V-shaped cavity. The yellow spectral range was achieved
      by intra-cavity frequency doubling using a LBO crystal. The laser could be tuned
      over a bandwidth of ~26 nm while exhibiting watt-level output powers. The maximum
      conversion efficiency from absorbed pump power to yellow output was 28% for
      continuous wave operation. The VECSEL's output could be modulated to generate
      optical pulses with duration down to 570 ns by directly modulating the pump
      laser. The high-power pulse operation is a key feature for astrophysics and
      medical applications while at the same time enables higher slope efficiency than
      continuous wave operation owing to decreased heating. 

PMID- 24663986
TI  - Phase-matched second harmonic generation at the Dirac point of a 2-D photonic
      crystal.
AB  - We study second harmonic generation in a 2-D photonic crystal with the pump field
      tuned at the Dirac point of the structure. The simultaneous generation of both
      forward and backward phase-matched second harmonic is achieved by exploiting a
      peculiar regime in which the interacting waves have zero phase velocity in the
      lattice. This regime can be attained even when strong material dispersion is
      present and therefore lends itself well to be implemented in semiconductor-based
      frequency conversion devices. A comparison between this method and the quasi
      phase-matching technique is also presented. 

PMID- 24663987
TI  - Simultaneous dispersion measurements of multiple fiber modes using virtual
      reference interferometry.
AB  - We present the simultaneous measurement of first and second order dispersion in
      short length (< 1 m) few mode fibers (polarization and transverse) using virtual
      reference interferometry. This technique generates results equivalent to balanced
      spectral interferometry, without the complexity associated with physical
      balancing. This is achieved by simulating a virtual reference with a group delay
      equal to that of the physical interferometer. The amplitude modulation that
      results from mixing the interferograms, generated in both the unbalanced
      interferometer and the virtual reference, is equivalent to the first order
      interference that would be produced by physical balancing. The advantages of the
      technique include speed, simplicity, convenience and the capability for
      simultaneous measurement of multiple modes. The theoretical framework is first
      developed and then verified experimentally. 

PMID- 24663988
TI  - Photon emission rate engineering using graphene nanodisc cavities.
AB  - In this work, we present a systematic study of the plasmon modes in a system of
      vertically stacked pair of graphene discs. Quasistatic approximation is used to
      model the eigenmodes of the system. Eigen-response theory is employed to explain
      the spatial dependence of the coupling between the plasmon modes and a quantum
      emitter. These results show a good match between the semi-analytical calculation
      and full-wave simulations. Secondly, we have shown that it is possible to
      engineer the decay rates of a quantum emitter placed inside and near this cavity,
      using Fermi level tuning, via gate voltages and variation of emitter location and
      polarization. We highlighted that by coupling to the bright plasmon mode, the
      radiative efficiency of the emitter can be enhanced compared to the single
      graphene disc case, whereas the dark plasmon mode suppresses the radiative
      efficiency. 

PMID- 24663989
TI  - 0.7 MW output power from a two-arm coherently combined Q-switched photonic
      crystal fiber laser.
AB  - We demonstrate a high peak power, Q-switched pulsed, intracavity coherently
      combined fiber laser system. The system is based on two Yb-doped, rod-type,
      photonic crystal fibers which are passively phase-locked and combined into the
      single output beam in a power oscillator configuration. Experimental evidence
      indicate that this oscillator system provides record high peak power of ~ 0.7 MW
      with pulse duration of ~ 10 ns at 1 kHz repetition rate. The measured beam
      quality shows near-diffraction-limited operation of the coherently combined
      system. 

PMID- 24663990
TI  - Nonequilibrium and thermal effects in mode-locked VECSELs.
AB  - Ultrafast femtosecond timescale dynamics in Vertical External Cavity Surface
      Emitting Lasers (VECSELs) have recently been employed to achieve record average
      power and duration mode-locked pulses by employing different types of saturable
      absorbers and Kerr Lens elements. Microscopic many-body dynamics are expected to
      dominate when attempting to push pulse durations below 100 fs. We present a
      preliminary microscopic simulation of ultrafast mode-locking in order to expose
      the role of hot carrier distributions in establishing ultrafast mode-locking. 

PMID- 24663991
TI  - Flat super-oscillatory lens for heat-assisted magnetic recording with sub-50 nm
      resolution.
AB  - Heat-assisted magnetic recording (HAMR) is a future roadmap technology to
      overcome the superparamagnetic limit in high density magnetic recording. Existing
      HAMR schemes depend on a simultaneous magnetic stimulation and light-induced
      local heating of the information carrier. To achieve high-density recorded data,
      near-field plasmonic transducers have been proposed as light concentrators. Here
      we suggest and investigate in detail an alternative approach exploiting a far
      field focusing device that can focus light into sub-50 nm hot-spots in the
      magnetic recording layer using a laser source operating at 473 nm. It is based on
      a recently introduced super-oscillatory flat lens improved with the use of solid
      immersion, giving an effective numerical aperture as high as 4.17. The proposed
      solution is robust and easy to integrate with the magnetic recording head thus
      offering a competitive advantage over plasmonic technology.

PMID- 24663992
TI  - At-wavelength metrology of hard X-ray mirror using near field speckle.
AB  - We present a method to measure the surface profile of hard X-ray reflective
      optics with nanometer height accuracy and sub-millimetre lateral resolution. The
      technique uses X-ray near-field speckle, generated by a scattering membrane
      translated using a piezo motor, to infer the deflection of X-rays from the
      surface. The method provides a nano-radian order accuracy on the mirror slopes in
      both the tangential and sagittal directions. As a demonstration, a pair of
      focusing mirrors mounted in a Kirkpatrick-Baez (KB) configuration were
      characterized and the results were in good agreement with offline metrology data.
      It is hoped that the new technique will provide feedback to optic manufacturers
      to improve mirror fabrication and be useful for the online optimization of
      active, nano-focusing mirrors on modern synchrotron beamlines.

PMID- 24663993
TI  - Switchable double wavelength generating vertical external cavity surface-emitting
      laser.
AB  - Switchable, double wavelength generation is demonstrated from a single vertical
      external cavity surface-emitting laser chip. Power of ~0.5 W for two wavelengths
      lambda~967 nm and 1,018 nm i.e. within the spectral distance of 51 nm were
      registered. In the semiconductor heterostructure a single set of nominally
      identical quantum wells was enclosed in a single, two-mode resonant microcavity.
      The wavelength switching was induced by the change of the pump power. The
      increase or decrease of the pump power changes the active region temperature and
      thus tunes spectrally the gain spectrum to the one of two modes.

PMID- 24663994
TI  - High-resolution long-reach distributed Brillouin sensing based on combined time
      domain and correlation-domain analysis.
AB  - A new scheme for distributed Brillouin sensing of strain and temperature in
      optical fibers is proposed, analyzed and demonstrated experimentally. The
      technique combines between time-domain and correlation-domain analysis. Both
      Brillouin pump and signal waves are repeatedly co-modulated by a relatively
      short, high-rate phase sequence, which introduces Brillouin interactions in a
      large number of discrete correlation peaks. In addition, the pump wave is also
      modulated by a single amplitude pulse, which leads to a temporal separation
      between the generation of different peaks. The Brillouin amplification of the
      signal wave at individual peak locations is resolved in the time domain. The
      technique provides the high spatial resolution and long range of unambiguous
      measurement offered by correlation-domain Brillouin analysis, together with
      reduced acquisition time through the simultaneous interrogation of a large number
      of resolution points. In addition, perfect Golomb codes are used in the phase
      modulation of the two waves instead of random sequences, in order to reduce noise
      due to residual, off-peak Brillouin interactions. The principle of the method is
      supported by extensive numerical simulations. Using the proposed scheme, the
      Brillouin gain spectrum is mapped experimentally along a 400 m-long fiber under
      test with a spatial resolution of 2 cm, or 20,000 resolution points, with only
      127 scans per choice of frequency offset between pump and signal. Compared with
      corresponding phase-coded, Brillouin correlation domain analysis schemes with
      equal range and resolution, the acquisition time is reduced by a factor of over
      150. A 5 cm-long hot spot, located towards the output end of the pump wave, is
      properly identified in the measurements. The method represents a significant
      advance towards practical high-resolution and long range Brillouin sensing
      systems. 

PMID- 24663995
TI  - Speckle reduction and maintaining contrast in a LASER pico-projector using a
      vibrating symmetric diffuser.
AB  - We proposed a design for a LASER pico-projector with a low speckle contrast value
      and high contrast ratio that maintains system efficiency. The method for speckle
      contrast reduction utilizes two diffusers and a Voice Coil Motor (VCM)
      oscillator. The two different diffusers for a high contrast ratio and high system
      efficiency can be divided into two categories. In Category 1, the speckle
      contrast value can be decreased to 2.80% by using a circular symmetric diffuser.
      At the same time, the full-on/full-off (FO:FO) contrast ratio can be maintained
      within 1200:1-1300:1, but the system efficiency decreases 1.50%. In Category 2,
      the speckle contrast value can be reduced to 6.50% by using an elliptically
      scattering diffuser. At the same time, the FO:FO contrast ratio can be maintained
      within 1300:1-1400:1, and the system efficiency decreases by only 1.00%.

PMID- 24663996
TI  - Generation of 1.024-Tb/s Nyquist-WDM phase-conjugated twin vector waves by a
      polarization-insensitive optical parametric amplifier for fiber-nonlinearity
      tolerant transmission.
AB  - We experimentally demonstrate the generation of 1.024-Tb/s Nyquist-WDM phase
      conjugated vector twin waves (PCTWs), consisting of eight 128-Gb/s polarization
      division-multiplexed QPSK signals and their idlers, by a broadband polarization
      insensitive fiber optic parametric amplifier. This novel all-optical signal
      processing approach to generate WDM-PCTWs enables a 2-fold reduction in the
      needed optical transmitters as compared to the conventional approach where each
      idler is generated by a dedicated transmitter. Digital coherent superposition of
      the twin waves at the receiver enables more than doubled reach in a dispersion
      managed transmission link. We further study the impact of polarization-mode
      dispersion on the performance gain brought by the phase-conjugated twin waves,
      showing a gain of ~3.8 dB in signal quality factors.

PMID- 24663997
TI  - Vibration-insensitive measurement of thickness variation of glass panels using
      double-slit interferometry.
AB  - A technique which can measure thickness variation of a moving glass plate in real
      time with nanometric resolution is proposed. The technique is based on the double
      slit interference of light. Owing to the nature of differential measurement
      scheme, the measurement system is immune to harsh environmental condition of a
      production line, and the measurement results are not affected by the swaying
      motion of the panel. With the preliminary experimental setup with scanning speed
      of 100 mm/s, the measurement repeatability was 3 nm for the waviness component of
      the thickness profile, filtered with a Gaussian filter with cutoff wavelength of
      8 mm. 

PMID- 24663998
TI  - Argand-plane vorticity singularities in complex scalar optical fields: an
      experimental study using optical speckle.
AB  - The Cornu spiral is, in essence, the image resulting from an Argand-plane map
      associated with monochromatic complex scalar plane waves diffracting from an
      infinite edge. Argand-plane maps can be useful in the analysis of more general
      optical fields. We experimentally study particular features of Argand-plane
      mappings known as "vorticity singularities" that are associated with mapping
      continuous single-valued complex scalar speckle fields to the Argand plane.
      Vorticity singularities possess a hierarchy of Argand-plane catastrophes
      including the fold, cusp and elliptic umbilic. We also confirm their connection
      to vortices in two-dimensional complex scalar waves. The study of vorticity
      singularities may also have implications for higher-dimensional fields such as
      coherence functions and multi-component fields such as vector and spinor fields.

PMID- 24663999
TI  - A systematic approach to enhance off-axis directional electromagnetic wave by two
      dimensional structure design.
AB  - In this study, we propose a two-dimensional (2D) dielectric structure tailored by
      a systematic design approach on the exit side of a metallic aperture to enhance
      the off-axis electromagnetic (EM) wave. We adopted a phase field method based
      topology optimization scheme and designed an arbitrary 2D dielectric structure in
      order to steer outward beaming through an aperture to a specific direction.
      Beyond previous one-dimensional structure, we proposed an arbitrary 2D dielectric
      structure through the introduced design process defining not only x- but also y
      directional dielectric structural boundaries simultaneously and experimentally
      confirmed enhanced EM wave transmission to a desired direction. 

PMID- 24664000
TI  - Wide-angle polarization-insensitive transparency of a continuous opaque metal
      film for near-infrared light.
AB  - Here we show that a continuous highly conducting metal film can be made
      transparent for wide-angle and polarization-insensitive incidence of near
      infrared light by depositing periodic metal patches on top of the metal film.
      Based on the optimized computations, the whole system could suppress the
      reflection and enhance the transmission. This design of transparent metal film
      can be useful in applications, such as optoelectronic electrodes, solar cells,
      and micro-electronic displays, where both high electrical conductivity and high
      optical transmittance are desirable. 

PMID- 24664001
TI  - Holographic head-mounted display with RGB light emitting diode light source.
AB  - A compact head-mounted holographic three-dimensional display with an RGB light
      emitting diode (LED) light source is developed. Issues regarding full-color
      holographic image design and the quality associated with the use of an LED light
      source are investigated. The accommodation effect and background noise in the
      proposed system are discussed based on experimental observation. 

PMID- 24664002
TI  - Integrated frequency comb source of heralded single photons.
AB  - We report an integrated photon pair source based on a CMOS-compatible microring
      resonator that generates multiple, simultaneous, and independent photon pairs at
      different wavelengths in a frequency comb compatible with fiber communication
      wavelength division multiplexing channels (200 GHz channel separation) and with a
      linewidth that is compatible with quantum memories (110 MHz). It operates in a
      self-locked pump configuration, avoiding the need for active stabilization,
      making it extremely robust even at very low power levels. 

PMID- 24664003
TI  - General hyperentanglement concentration for photon systems assisted by quantum
      dot spins inside optical microcavities.
AB  - Hyperentanglement is a promising resource in quantum information processing,
      especially for increasing the channel capacity of long-distance quantum
      communication. Here we present a general hyper-entanglement concentration
      protocol (hyper-ECP) for nonlocal partially hyperentangled Bell states that decay
      with the interrelationship between the polarization and the spatial-mode degrees
      of freedom of two-photon systems, which is not taken into account in other hyper
      ECPs, resorting to the optical property of the quantum-dot spins inside one-side
      optical microcavities. We show that the success probability of our hyper-ECP is
      largely increased by iteration of the hyper-ECP process. Our hyper-ECP can be
      straightforwardly generalized to distill nonlocal maximally hyperentangled N
      photon Greenberger-Horne-Zeilinger (GHZ) states from arbitrary partially
      hyperentangled GHZ-class states.

PMID- 24664004
TI  - Evaluation of modal noise in graded-index silica and plastic optical fiber links
      for radio over multimode fiber systems.
AB  - We have evaluated and compared modal noise induced in a graded-index silica
      multimode fiber (GI-MMF) link and a graded-index plastic optical fiber (GI-POF)
      link with the misaligned fiber connections. In radio over fiber (RoF) systems
      using these optical fibers, modal noise appears as unwanted amplitude modulation
      in the received signal, and results in degradation of the RoF transmission
      performance. In this work, we have evaluated the modal noise induced in GI-MMFs
      and GI-POFs with its same core diameter of 50 MUm. Our results show that GI-POFs
      have an inherently higher tolerance to misaligned connection and less modal noise
      than GI-MMFs in terms of both the error-vector magnitude and the speckle pattern
      of the transmitted signals.

PMID- 24664005
TI  - Evolution of branch points for a laser beam propagating through an uplink
      turbulent atmosphere.
AB  - Evolution of branch points in the distorted optical field is studied when a laser
      beam propagates through turbulent atmosphere along an uplink path. Two categories
      of propagation events are mainly explored for the same propagation height: fixed
      wavelength with change of the turbulence strength and fixed turbulence strength
      with change of the wavelength. It is shown that, when the beam propagates to a
      certain height, the density of the branch-points reaches its maximum and such a
      height changes with the turbulence strength but nearly remains constant with
      different wavelengths. The relationship between the density of branch-points and
      the Rytov number is also given. A fitted formula describing the relationship
      between the density of branch-points and propagation height with different
      turbulence strength and wavelength is found out. Interestingly, this formula is
      very similar to the formula used for describing the Blackbody radiation in
      physics. The results obtained may be helpful for atmospheric optics, astronomy
      and optical communication. 

PMID- 24664006
TI  - Self-Q-switched, orthogonally polarized, dual-wavelength laser using long
      lifetime Yb3+ crystal as both gain medium and saturable absorber.
AB  - A novel self-Q-switched and orthogonally polarized dual-wavelength laser has been
      investigated with Yb3+-doped CGB disordered crystals. By slightly inclining
      output coupler to introduce the Fresnel loss, we realized simultaneously dual
      wavelength laser operation at 1052.6 nm in E//b polarization and 1057.7 nm in
      E//c polarization with a frequency difference of 1.38 THz. Self-Q-switched pulse
      generation was observed in this free-running laser, originating from the
      nonlinear reabsorption effect of Yb:CGB as well as the strong storage of
      inversion population induced by the long excited-state lifetime (~1 ms). Pulse
      duration of 287 ns was obtained with an output average power of 416 mW and a
      repetition rate of 35 kHz. The self-Q-switching effect increased the peak power
      by 100 times the average power. This very simple laser, free from the complexity
      and high-cost of additional intracavity polarization modulator and Q-switcher,
      may be applied for constructing miniature, integrated and portable laser system.

PMID- 24664007
TI  - Surface angular momentum of light beams.
AB  - Traditionally, the angular momentum of light is calculated for "bullet-like"
      electromagnetic wave packets, although in actual optical experiments "pencil
      like" beams of light are more commonly used. The fact that a wave packet is
      bounded transversely and longitudinally while a beam has, in principle, an
      infinite extent along the direction of propagation, renders incomplete the
      textbook calculation of the spin/orbital separation of the angular momentum of a
      light beam. In this work we demonstrate that a novel, extra surface part must be
      added in order to preserve the gauge invariance of the optical angular momentum
      per unit length. The impact of this extra term is quantified by means of two
      examples: a Laguerre-Gaussian and a Bessel beam, both circularly polarized.

PMID- 24664008
TI  - Absolute distance measurement by dual-comb nonlinear asynchronous optical
      sampling.
AB  - A dual-comb nonlinear asynchronous optical sampling method is proposed to
      simplify determination of the time interval and extend the non-ambiguity range in
      absolute length measurements. Type II second harmonic generation facilitates
      curve fitting in determining the time interval between adjacent pulses.
      Meanwhile, the non-ambiguity range is extended by adjusting the repetition rate
      of the signal laser. The performance of the proposed method is compared with a
      heterodyne interferometer. Results show that the system achieves a maximum
      residual of 100.6 nm and an uncertainty of 1.48 MUm in a 0.5 ms acquisition time.
      With longer acquisition time, the uncertainty can be reduced to 166.6 nm for 50
      ms and 82.9 nm for 500 ms. Moreover, the extension of the non-ambiguity range is
      demonstrated by measuring an absolute distance beyond the inherent range
      determined by the fixed repetition rate.

PMID- 24664009
TI  - High-power and highly efficient operation of wavelength-tunable Raman fiber
      lasers based on volume Bragg gratings.
AB  - Highly efficient and high-power operation of Raman fiber lasers in fixed
      wavelength and wavelength-tunable cavity configurations based on a graded-index
      multimode fiber is reported. Fixed-wavelength and wavelength tunable operating
      regimes are achieved using volume Bragg gratings (VBGs) with center wavelengths
      of 1658 nm and 1750 nm, respectively. The fixed-wavelength laser yielded a
      maximum output power of 10.5 W at 1658.3 nm with a FWHM linewidth of ~0.1 nm for
      the launched pump power of 23.4 W, corresponding to a slope efficiency of 82.7%
      with respect to the launched pump power. The measured beam quality in the form of
      M2 factor is ~1.35, corresponding to the fundamental mode of the fiber. For the
      wavelength-tunable Raman fiber laser, a wavelength tuning range of 37 nm from
      1638.5 to 1675.1 nm is obtained with a maximum output power of 3.6 W at 1658.5 nm
      for the launched pump power of 13.0 W.

PMID- 24664010
TI  - Polarization-selectable cavity locking method for generation of laser Compton
      scattered gamma-rays.
AB  - Nowadays, generation of energy-tunable, monochromatic gamma-rays is needed to
      establish a nondestructive assay method of nuclear fuel materials. The gamma-rays
      are generated by collision of laser photons stored in a cavity and relativistic
      electrons. We propose a configuration of an enhancement cavity capable of
      performing polarization control fabricated by a combination of a four-mirror ring
      cavity with a small spot inside a cavity and a three-mirror of reflective optics
      as an image inverter for polarization-selectable gamma-rays. The image inverter
      introduces a phase shift of specific polarization which can be used to generate
      an error signal to lock an optical cavity at a resonance condition. 

PMID- 24664011
TI  - Moment-generating function method used to accurately evaluate the impact of the
      linearized optical noise amplified by EDFAs.
AB  - In a nonlinear optical fiber communication (OFC) system with signal power much
      stronger than noise power, the noise field in the fiber can be described by
      linearized noise equation (LNE). In this case, the noise impact on the system
      performance can be evaluated by moment-generating function (MGF) method. Many
      published MGF calculations were based on the LNE using continuous wave (CW)
      approximation, where the modulated signal needs to be artificially simplified as
      an unmodulated signal. Results thus obtained should be treated carefully.
      Reliable results can be obtained by replacing the CW-based LNE with the accurate
      LNE proposed by Holzlohner et al in Ref. [1]. In this work we show that, for the
      case of linearized noise amplified by EDFAs, its MGF can be obtained by
      calculating the noise propagator directly from the accurate LNE. Our results
      agree well with the experimental data of multi-span DPSK systems.

PMID- 24664012
TI  - Two approaches for ultrafast random bit generation based on the chaotic dynamics
      of a semiconductor laser.
AB  - This paper reports the experimental investigation of two different approaches to
      random bit generation based on the chaotic dynamics of a semiconductor laser with
      optical feedback. By computing high-order finite differences of the chaotic laser
      intensity time series, we obtain time series with symmetric statistical
      distributions that are more conducive to ultrafast random bit generation. The
      first approach is guided by information-theoretic considerations and could
      potentially reach random bit generation rates as high as 160 Gb/s by extracting 4
      bits per sample. The second approach is based on pragmatic considerations and
      could lead to rates of 2.2 Tb/s by extracting 55 bits per sample. The randomness
      of the bit sequences obtained from the two approaches is tested against three
      standard randomness tests (ENT, Diehard, and NIST tests), as well as by
      calculating the statistical bias and the serial correlation coefficients on
      longer sequences of random bits than those used in the standard tests. 

PMID- 24664013
TI  - An SOI based polarization insensitive filter for all-optical clock recovery.
AB  - We fabricate and demonstrate a compact polarization insensitive filter for all
      optical clock recovery (CR) based on silicon-on-insulator (SOI), which consists
      of a microring resonator (MRR) and two modified two-dimensional (2D) grating
      couplers. The distributed Bragg reflectors (DBRs) are introduced to improve the
      coupling efficiency of the 2D grating coupler. The MRR works as a comb filter for
      CR, while the 2D grating couplers serve as the polarization diversity unit to
      achieve a polarization insensitive operation. A subsequent semiconductor optical
      amplifier (SOA) performs the amplitude equalization. Based on this scheme, a good
      clock signal with 970 fs timing jitter can be achieved at 44 Gb/s from input
      signals with arbitrary polarization states.

PMID- 24664014
TI  - Application of flat-top focus to 2D trapping of large particles.
AB  - The 2D optical trapping ability of larger-than average-particles is compared for
      three different beam types: a flat-top, a Gaussian beam, and a donut shaped beam.
      Optical force-displacement curves are calculated in four different size regimes
      of particle diameters (1.5-20 MUm). We find that the trapping efficiency
      increases linearly with ratio of particle diameter to wavelength for all three
      beams. As the ratio reaches a specific threshold value, the flat-top focus
      exhibits the largest trapping efficiency compared to the other two beam types. We
      experimentally demonstrate that flat-top focusing provides the largest transverse
      trapping efficiency for particles as large as 20 MUm in diameter for our given
      experimental conditions. The overall trend in our experimental results follows
      that observed in our simulation model. The results from this study could
      facilitate light manipulation of large particles.

PMID- 24664015
TI  - High throughput holographic imaging-in-flow for the analysis of a wide plankton
      size range.
AB  - We developed a Digital Holographic Microscope (DHM) working with a partial
      coherent source specifically adapted to perform high throughput recording of
      holograms of plankton organisms in-flow, in a size range of 3 um-300 um, which is
      of importance for this kind of applications. This wide size range is achieved
      with the same flow cell and with the same microscope magnification. The DHM
      configuration combines a high magnification with a large field of view and
      provides high-resolution intensity and quantitative phase images refocusing on
      high sample flow rate. Specific algorithms were developed to detect and extract
      automatically the particles and organisms present in the samples in order to
      build holograms of each one that are used for holographic refocusing and
      quantitative phase contrast imaging. Experimental results are shown and
      discussed.

PMID- 24664016
TI  - A 40 Gbit/s optical link on a 300-mm silicon platform.
AB  - We demonstrated 40 Gbit/s optical link by coupling a silicon (Si) optical
      modulator to a germanium (Ge) photo-detector from two separate photonic chips.
      The optical modulator was based on carrier depletion in a pn diode integrated in
      a 950-um long Mach-Zehnder interferometer. The Ge photo-detector was a lateral
      pin diode butt coupled to a silicon waveguide. The overall loss, which is mainly
      due to coupling (3 grating couplers times ~4 dB) was estimated to be lower than
      18 dB. That also included modulator loss (4.9-dB) and propagation loss (<1
      dB/cm). Both optoelectronic devices have been fabricated on a 300-mm CMOS
      platform to address high volume production markets.

PMID- 24664017
TI  - Plasmon resonances in a stacked pair of graphene ribbon arrays with a lateral
      displacement.
AB  - We find that a stacked pair of graphene ribbon arrays with a lateral displacement
      can excite plasmon waveguide mode in the gap between ribbons, as well as surface
      plasmon mode on graphene ribbon surface. When the resonance wavelengthes of
      plasmon waveguide mode and surface plasmon mode are close to each other, there is
      a strong electromagnetic interaction between the two modes, and then they
      contribute together to transmission dip. The plasmon waveguide mode resonance can
      be manipulated by the lateral displacement and longitudinal interval between
      arrays due to their influence on the manner and strength of electromagnetic
      coupling between two arrays. The findings expand our understanding of
      electromagnetic resonances in graphene-ribbon array structure and may affect
      further engineering of nanoplasmonic devices and metamaterials.

PMID- 24664018
TI  - Polarization independent broadband femtosecond optical gating using transient
      Kerr lens effect.
AB  - A convenient polarization independent, broadband femtosecond optical gating
      technique utilizing transient Kerr lens effect is demonstrated by measuring the
      chirp structure of linearly polarized or non-polarized white light continuum
      generated in water and a photonic crystal fiber, respectively. Comparing with
      previous time-resolved spectroscopic techniques, this Kerr lens gating method is
      not limited by the requirement of specific nonlinear media with broadband
      response, critical phase-matching conditions, and especially the pump-probe
      polarization relationship. By replacing the white light continuum with other
      broadband light signals of interest, this method can be exploited in other
      femtosecond time-resolved spectroscopy, e.g., femtosecond photoluminescence. 

PMID- 24664019
TI  - Pulse bursts with a controllable number of pulses from a mode-locked Yb-doped all
      fiber laser system.
AB  - Pulse bursts with a controllable number of pulses per burst have been produced
      directly from a mode-locked Yb-doped fiber laser for the first time. Each output
      burst contained numerous pulses with a high pulse repetition rate of 29.4 MHz.
      The duration of a single pulse was 680 ps. The pulse burst had a repetition rate
      of 251.6 kHz. The pulse burst could easily be further amplified to a total pulse
      burst energy of ~795 nJ, corresponding to a total average power of 200 mW. 

PMID- 24664020
TI  - Thermal lens evolution and compensation in a high power KGW Raman laser.
AB  - The transient thermal lens in a high-average power double metal tungstate Raman
      laser has been investigated. An external cavity potassium gadolinium tungstate
      (KGW) laser designed for second-Stokes output was burst-pumped with up to 46 W of
      average power at a pulse repetition rate of 38 kHz. At low duty-cycle, the laser
      generated up to 18 W of on-time average Raman power with a conversion efficiency
      of 40%. At high duty cycle, efficiency is reduced and the near-field beam profile
      expands in the X1' crystal direction over a period of tens of milliseconds. The
      evolution of the spatial beam properties occurs in response to the development of
      a highly astigmatic thermal lens with fast-axis susceptibility of approximately 
      1.7 m-1 per watt of Raman output power. We show that the likely cause for
      astigmatism is primarily photo-elastic in origin. Beam circularization was
      achieved by incorporating an intracavity convex cylindrical lens.

PMID- 24664021
TI  - Isolating quantum coherence using coherent multi-dimensional spectroscopy with
      spectrally shaped pulses.
AB  - We demonstrate how spectral shaping in coherent multidimensional spectroscopy can
      isolate specific signal pathways and directly access quantitative details. By
      selectively exciting pathways involving a coherent superposition of exciton
      states we are able to identify, isolate and analyse weak coherent coupling
      between spatially separated excitons in an asymmetric double quantum well.
      Analysis of the isolated signal elucidates details of the coherent interactions
      between the spatially separated excitons. With a dynamic range exceeding 10(4) in
      electric field amplitude, this approach facilitates quantitative comparisons of
      different signal pathways and a comprehensive description of the electronic
      states and their interactions.

PMID- 24664022
TI  - Optimised quantum hacking of superconducting nanowire single-photon detectors.
AB  - We explore bright-light control of superconducting nanowire single-photon
      detectors (SNSPDs) in the shunted configuration (a practical measure to avoid
      latching). In an experiment, we simulate an illumination pattern the SNSPD would
      receive in a typical quantum key distribution system under hacking attack. We
      show that it effectively blinds and controls the SNSPD. The transient blinding
      illumination lasts for a fraction of a microsecond and produces several
      deterministic fake clicks during this time. This attack does not lead to elevated
      timing jitter in the spoofed output pulse, and hence does not introduce
      significant errors. Five different SNSPD chip designs were tested. We consider
      possible countermeasures to this attack.

PMID- 24664023
TI  - Performance analysis of blind timing phase estimators for digital coherent
      receivers.
AB  - The performances of various blind timing phase estimators (TPE) for digital
      coherent receiver are analyzed. The equivalence among four TPE algorithms is
      analytically presented, showing that two TPE algorithms applying squaring pre
      filters are in fact identical. Three TPE algorithms applicable to Nyquist signals
      are proposed based on the equivalence analysis. In addition, the impact of
      receiver bandwidths, spectrum weighting bandwidths and signal timing phases on
      TPE performance are investigated. The definition of sampling diversity and the
      analysis of sampling diversity gain for four pulse shapes are presented. The
      effect of sampling diversity is observed and verified via both simulations and
      experiments. 

PMID- 24664024
TI  - Mode-locked operation of Cr4+:YAG single-crystal fiber laser with external
      cavity.
AB  - We report what is to our knowledge the first mode-locked Cr4+:YAG single-crystal
      fiber laser, which generates pulses of 120-fs duration with an output power of 23
      mW at a center wavelength of 1520 nm for a single pulse in a cavity-round-trip.
      The laser contains a single-crystal fiber multi-mode waveguide about 120 MUm in
      diameter and 40-mm long. The fundamental transverse mode is selected with an
      external cavity. This design strategy turned out to be well suited for direct
      high-power-laser-diode pumping.

PMID- 24664025
TI  - Bistability of time-periodic polarization dynamics in a free-running VCSEL.
AB  - We report experimentally a bistability between two limit cycles (i.e. time
      periodic dynamics) in a free-running vertical-cavity surface-emitting laser. The
      two limit cycles originate from a bifurcation on two elliptically polarized
      states which exhibit a small frequency difference and whose main axes are
      symmetrical with respect to the linear polarization eigenaxes at threshold. We
      demonstrate theoretically that this peculiar behavior can be explained in the
      framework of the spin-flip model model by taking into account a small
      misalignment between the phase and amplitude anisotropies. 

PMID- 24664026
TI  - Fano resonances in a multimode waveguide coupled to a high-Q silicon nitride ring
      resonator.
AB  - Silicon nitride (Si3N4) optical ring resonators provide exceptional opportunities
      for low-loss integrated optics. Here we study the transmission through a
      multimode waveguide coupled to a Si3N4 ring resonator. By coupling single-mode
      fibers to both input and output ports of the waveguide we selectively excite and
      probe combinations of modes in the waveguide. Strong asymmetric Fano resonances
      are observed and the degree of asymmetry can be tuned through the positions of
      the input and output fibers. The Fano resonance results from the interference
      between modes of the waveguide and light that couples resonantly to the ring
      resonator. We develop a theoretical model based on the coupled mode theory to
      describe the experimental results. The large extension of the optical modes out
      of the Si3N4 core makes this system promising for sensing applications.

PMID- 24664027
TI  - Photonic crystal waveguide cavity with waist design for efficient trapping and
      detection of nanoparticles.
AB  - For manipulating nanometric particles, we propose a photonic crystal waveguide
      cavity design with a waist structure to enhance resonance characteristic of the
      cavity. For trapping a polystyrene particle of 50 nm radius on the lateral side
      of the waist, the optical force can reach 2308 pN/W with 24.7% signal
      transmission. Threshold power of only 0.32 mW is required for stable trapping.
      The total length of the device is relatively short with only ten photonic crystal
      periods, and the trapping can occur precisely and only at the waist. The designed
      cavity can also provide particle detection and surrounding medium sensing using
      the transmission spectrum with narrow linewidth. The simulated figure of merit of
      110.6 is relatively high compared with those obtained from most plasmonic
      structures for sensing application. We anticipate this design with features of
      compact, efficient, and versatile in functionality will be beneficial for
      developing lab-on-chip in the future. 

PMID- 24664028
TI  - Mid-IR beam direction stabilization scheme for vibrational spectroscopy,
      including dual-frequency 2DIR.
AB  - A compact laser beam direction stabilization scheme is developed that provides
      the angular stability of better than 50 MUrad over a wide range of frequencies
      from 800 to 4000 cm-1. The schematic is fully automated and features a single MCT
      quadrant detector. The schematic was tested to stabilize directions of the two IR
      beams used for dual-frequency two-dimensional infrared (2DIR) measurements and
      showed excellent results: automatic tuning of the beam direction allowed
      achieving the alignment quality within 10% of the optimal alignment obtained
      manually. The schematic can be easily implemented to any nonlinear spectroscopic
      measurements in the mid-IR spectral region.

PMID- 24664029
TI  - Demonstration of suppressed phonon tunneling losses in phononic bandgap shielded
      membrane resonators for high-Q optomechanics.
AB  - Dielectric membranes with exceptional mechanical and optical properties present
      one of the most promising platforms in quantum opto-mechanics. The performance of
      stressed silicon nitride nanomembranes as mechanical resonators notoriously
      depends on how their frame is clamped to the sample mount, which in practice
      usually necessitates delicate, and difficult-to-reproduce mounting solutions.
      Here, we demonstrate that a phononic bandgap shield integrated in the membrane's
      silicon frame eliminates this dependence, by suppressing dissipation through
      phonon tunneling. We dry-etch the membrane's frame so that it assumes the form of
      a cm-sized bridge featuring a 1-dimensional periodic pattern, whose phononic
      density of states is tailored to exhibit one, or several, full band gaps around
      the membrane's high-Q modes in the MHz-range. We quantify the effectiveness of
      this phononic bandgap shield by optical interferometry measuring both the
      suppressed transmission of vibrations, as well as the influence of frame clamping
      conditions on the membrane modes. We find suppressions up to 40 dB and, for three
      different realized phononic structures, consistently observe significant
      suppression of the dependence of the membrane's modes on sample clamping-if the
      mode's frequency lies in the bandgap. As a result, we achieve membrane mode
      quality factors of 5 * 10(6) with samples that are tightly bolted to the 8 K-cold
      finger of a cryostat. Q * f -products of 6 * 10(12) Hz at 300 K and 14 * 10(12)
      Hz at 8 K are observed, satisfying one of the main requirements for optical
      cooling of mechanical vibrations to their quantum ground-state.

PMID- 24664030
TI  - Low-noise parametric frequency comb for continuous C-plus-L-band 16-QAM channels
      generation.
AB  - A low phase noise frequency comb generated from a continuous-wave seed is
      experimentally demonstrated across continuous C- and L-bands. Parametrically
      generated carriers with optical signal-to-noise ratio in excess of 45 dB were
      used to generate 16-ary quadrature amplitude modulated signals. We characterize
      20 GBaud channels' performance that was varied by only 1.7 dB across the combined
      C/L band.

PMID- 24664031
TI  - Signal processing method based on group delay calculation for distributed Bragg
      wavelength shift in optical frequency domain reflectometry.
AB  - A signal processing method based on group delay calculations is introduced for
      distributed measurements of long-length fiber Bragg gratings (FBGs) based on
      optical frequency domain reflectometry (OFDR). Bragg wavelength shifts in
      interfered signals of OFDR are regarded as group delay. By calculating group
      delay, the distribution of Bragg wavelength shifts is obtained with high
      computational efficiency. We introduce weighted averaging process for noise
      reduction. This method required only 3.5% of signal processing time which was
      necessary for conventional equivalent signal processing based on short-time
      Fourier transform. The method also showed high sensitivity to experimental
      signals where non-uniform strain distributions existed in a long-length FBG.

PMID- 24664032
TI  - Simultaneously improving the sensitivity and absolute accuracy of CPT
      magnetometer.
AB  - A new method to improve the sensitivity and absolute accuracy simultaneously for
      coherent population trapping (CPT) magnetometer based on the differential
      detection method is presented. Two modulated optical beams with orthogonal
      circular polarizations are applied, in one of which two magnetic resonances are
      excited simultaneously by modulating a 3.4GHz microwave with Larmor frequency.
      When a microwave frequency shift is introduced, the difference in the power
      transmitted through the cell in each beam shows a low noise resonance. The
      sensitivity of 2pT/Hz @ 10Hz is achieved. Meanwhile, the absolute accuracy of +/-
      0.5nT within the magnetic field ranging from 20000nT to 100000nT is realized.

PMID- 24664033
TI  - An efficient hybrid method for scattering from arbitrary dielectric objects
      buried under a rough surface: TM case.
AB  - A hybrid method combining the finite element method (FEM) with the boundary
      integral equation (BIE) is presented in this paper to investigate two-dimensional
      (2D) electromagnetic scattering properties of multiple dielectric objects buried
      beneath a dielectric rough ground for TM case. In traditional FEM simulation, the
      artificial boundaries, such as perfectly matched layer (PML) and the absorbing
      boundary conditions (ABC), are usually adopted as truncated boundaries to enclose
      the whole model. However, the enclosed computational domain increases quickly in
      size for a rough surface with a large scale, especially for the scattering model
      of objects away from the rough surface. In the hybrid FEM-BIE method, one
      boundary integral equation is adopt to depict the scattering above the rough
      surface based on Green's function. Based on the domain decomposition technique,
      the computational region below the rough ground is divided into multiple isolated
      interior regions containing each object and the exterior region. Finite element
      formulations are only applied inside interior regions to derive a set of linear
      systems, and another boundary integral formula is developed below the rough
      surface which also acts as the boundary constraint of the FEM region. Compared
      with traditional FEM, the hybrid technique presented here is highly efficient in
      terms of computational memory, time, and versatility. Numerical simulations are
      carried out based on hybrid FEM-BIE to study the scattering from multiple
      dielectric objects buried beneath a rough ground.

PMID- 24664034
TI  - Synthesis of highly focused fields with circular polarization at any transverse
      plane.
AB  - We develop a method for generating focused vector beams with circular
      polarization at any transverse plane. Based on the Richards-Wolf vector model, we
      derive analytical expressions to describe the propagation of these set of beams
      near the focal area. Since the polarization and the amplitude of the input beam
      are not uniform, an interferometric system capable of generating spatially
      variant polarized beams has to be used. In particular, this wavefront is
      manipulated by means of spatial light modulators displaying computer generated
      holograms and subsequently focused using a high numerical aperture objective
      lens. Experimental results using a NA = 0.85 system are provided: irradiance and
      Stokes images of the focused field at different planes near the focal plane are
      presented and compared with those obtained by numerical simulation. 

PMID- 24664035
TI  - Femtosecond pulse generation from a topological insulator mode-locked fiber
      laser.
AB  - We reported on the generation of femtosecond pulse in a fiber ring laser by using
      a polyvinyl alcohol (PVA)-based topological insulator (TI), Bi2Se3 saturable
      absorber (SA). The PVA-TI composite has a low saturable optical intensity of 12
      MW/cm2 and a modulation depth of ~3.9%. By incorporating the fabricated PVA-TISA
      into a fiber laser, mode-locking operation could be achieved at a low pump
      threshold of 25 mW. After an optimization of the cavity parameters, optical pulse
      with ~660 fs centered at 1557.5 nm wavelength had been generated. The
      experimental results demonstrate that the PVA could be an excellent host material
      for fabricating high-performance TISA, and also indicate that the filmy PVA-TISA
      is indeed a good candidate for ultrafast saturable absorption device.

PMID- 24664036
TI  - Optical signal to noise ratio monitoring using single channel sampling technique.
AB  - In this paper, we propose a novel method to depict 2-dimension (2-D) phase
      portrait by using single-channel-sampling (SCS) technique, which can be used for
      optical performance monitoring. Single low speed sampling scheme reduces cost and
      complexity of monitoring system setup significantly. In the experimental
      demonstration, optical signal to noise ratio (OSNR) is monitored from 10 dB to 30
      dB by statistical analysis on pattern evolution of the generated 2-D phase
      portrait in both NRZ and RZ systems. The chromatic dispersion (CD) influence on
      OSNR monitoring performance is also investigated.

PMID- 24664037
TI  - Quasi-droplet microbubbles for high resolution sensing applications.
AB  - Optical properties and sensing capabilities of fused silica microbubbles were
      studied numerically using a finite element method. Mode characteristics, such as
      quality factor (Q) and effective refractive index, were determined for different
      bubble diameters and shell thicknesses. For sensing applications with whispering
      gallery modes (WGMs), thinner shells yield improved sensitivity. However, the Q
      factor decreases with reduced thickness and this limits the final resolution.
      Three types of sensing applications with microbubbles, based on their optimized
      geometrical parameters, were studied. Herein the so-called quasi-droplet regime
      is defined and discussed. It is shown that best resolution can be achieved when
      microbubbles act as quasi-droplets, even for water-filled cavities at the
      telecommunications C-band. 

PMID- 24664038
TI  - Quantitative description of the self-healing ability of a beam.
AB  - Quantitative description of the self-healing ability of a beam is very important
      for studying or comparing the self-healing ability of different beams. As
      describing the similarity by using the angle of two infinite-dimensional complex
      vectors in Hilbert space, the angle of two intensity profiles is proposed to
      quantitatively describe the self-healing ability of different beams. As a special
      case, quantitative description of the self-healing ability of a Bessel-Gaussian
      beam is studied. Results show that the angle of two intensity profiles can be
      used to describe the self-healing ability of arbitrary beams as the
      reconstruction distance for quantitatively describing the self-healing ability of
      Bessel beam. It offers a new method for studying or comparing the self-healing
      ability of different beams. 

PMID- 24664039
TI  - Relaxation and square-wave oscillations in a semiconductor laser with
      polarization rotated optical feedback.
AB  - The rate equations for a laser with a polarization rotated optical feedback are
      investigated both numerically and analytically. The frequency detuning between
      the polarization modes is now taken into account and we review all earlier
      studies in order to motivate the range of values of the fixed parameters. We find
      that two basic Hopf bifurcations leading to either stable sustained relaxation or
      square-wave oscillations appear in the detuning versus feedback rate diagram. We
      also identify two key parameters describing the differences between the total
      gains of the two polarization modes and discuss their effects on the periodic
      square-waves.

PMID- 24664040
TI  - Saturated gain spectrum of VECSELs determined by transient measurement of lasing
      onset.
AB  - We describe time-resolved measurements of the evolution of the spectrum of
      radiation emitted by an optically-pumped continuous-wave InGaAs-GaAs quantum well
      laser, recorded as lasing builds up from noise to steady state. We extract a
      fitting parameter corresponding to the gain dispersion of the parabolic spectrum
      equal to -79 +/- 30 fs2 and -36 +/- 6 fs2 for a resonant and anti-resonant
      structure, respectively. Furthermore the recorded evolution of the spectrum
      allows for the calculation of an effective FWHM gain bandwidth for each
      structure, of 11 nm and 18 nm, respectively.

PMID- 24664041
TI  - Power budget improvement of symmetric 40-Gb/s DML-based TWDM-PON system.
AB  - We propose a symmetric 40-Gb/s time and wavelength division multiplexed passive
      optical network (TWDM-PON) system with directly modulated laser (DML) as both
      downstream and upstream transmitters. A single bi-pass delay interferometer (DI),
      deployed in the optical line terminal (OLT), is used to mitigate multiple
      channels' signal distortions induced by laser chirp and fiber chromatic
      dispersion. With the help of the DI, we successfully demonstrate error-free
      transmission with the aggregate capacity of 40 Gb/s over different transmission
      distance. And in back-to-back case, by using a 0.2-nm free spectrum range (FSR)
      DI, ~11 dB optical power budget improvement is achieved at a bit error ratio of
      1e-3. Owing to this high power budget, the maximum reach can be extended to 50 km
      for 1024 splits, 75 km for 256 splits, and 100 km for 64 splits. Meanwhile, the
      impacts of FSR of DI and laser wavelength shift on system performance are
      investigated in terms of receiver sensitivity. It is shown that, our system can
      achieve more than 43-dB power budget and support +/- 2.5-GHz wavelength shift
      when the FSR is less than 0.2 nm.

PMID- 24664042
TI  - A concomitant and complete set of nonvolatile all-optical logic gates based on
      hybrid spatial solitons.
AB  - We theoretically demonstrate the realization of a complete canonical set of all
      optical logic gates (AND, OR, NOT), with a persistent (stored) output, by
      combining propagative spatial solitons in a photorefractive crystal and
      dissipative cavity solitons in a downstream broad-area vertical cavity surface
      emitting laser (VCSEL). The system uses same-color, optical-axis aligned input
      and output channels with fixed readout locations, while switching from one gate
      to another is achieved by simply varying the potential applied to the
      photorefractive crystal. The inputs are Gaussian beams launched in the
      photorefractive crystal and the output is a bistable, persistent soliton in the
      VCSEL with a 'robust' eye diagram and large signal-to-noise ratio (SNR). Fast
      switching and intrinsic parallelism suggest that high bit flow rates can be
      obtained.

PMID- 24664043
TI  - Hemispherical digital optical condensers with no lenses, mirrors, or moving
      parts.
AB  - We present a simple method for obtaining direct non-scanning images in the far
      field with subwavelength resolution. Our approach relies on the use of a digital
      optical condenser comprised of an array of light emitting diodes uniformly
      distributed inside of a hollow hemisphere. We demonstrate experimental
      observation of minimum feature sizes of the order of lambda/6 with the proposed
      technique. Although our experiments were performed at visible frequencies, we
      anticipate that the proposed approach to subwavelength resolution can be extended
      to the ultraviolet and infrared spectral regions. 

PMID- 24664044
TI  - Demonstration of electro-optic half-adder using silicon photonic integrated
      circuits.
AB  - We report a silicon photonic integrated circuit which can perform the operation
      of half-adder based on two cascaded microring resonators (MRRs). PIN diodes
      embedded around MRRs are employed to achieve the carrier injection modulation.
      Two electrical pulse sequences representing the two operands of the half-add
      operation are applied to PIN diodes to modulate two MRRs through the plasma
      dispersion effect. The final operation results of bitwise Sum and Carry operation
      are output at two different output ports of the device. Microheaters fabricated
      on the top of MRRs are employed to compensate two MRRs resonance mismatch caused
      by the fabrication error through the thermo-optic effect. Addition operation of
      two bits with the operation speed of 100 Mbps is demonstrated.

PMID- 24664045
TI  - A nonlinear plasmonic resonator for three-state all-optical switching.
AB  - A nonlinear plasmonic resonator design is proposed for three-state all-optical
      switching at frequencies including near infrared and lower red parts of the
      spectrum. The tri-stable response required for three-state operation is obtained
      by enhancing nonlinearities of a Kerr medium through multiple (higher order)
      plasmons excited on resonator's metallic surfaces. Indeed, simulations
      demonstrate that exploitation of multiple plasmons equips the proposed resonator
      with a multi-band tri-stable response, which cannot be obtained using existing
      nonlinear plasmonic devices that make use of single mode Lorentzian resonances.
      Multi-band three-state optical switching that can be realized using the proposed
      resonator has potential applications in optical communications and computing. 

PMID- 24664046
TI  - Manipulation of quadratic cascading processes in a locally quasi-periodic chi(2)
      medium.
AB  - We theoretically and numerically investigate the quadratic cascading effect of
      third-harmonic (TH) generation in a locally quasi-periodic nonlinear photonic
      structure. We study the effect of structure parameters on the acceptance
      bandwidth and conversion efficiency of the cascading process. We demonstrate that
      the conversion efficiency of the cascading process can be enhanced by using a
      longer locally quasi-periodic nonlinear photonic crystal, without adversely
      affecting the acceptance bandwidth of the emitted radiation. 

PMID- 24664047
TI  - Electronic dispersion compensation in a 50 Gb/s optically unamplified direct
      detection receiver enabled by vestigial-sideband orthogonal frequency division
      multiplexing.
AB  - We present a novel method for dispersion compensation based on vestigial-sideband
      transmission of an orthogonal frequency division multiplexed signal through
      standard signal-mode fiber with a direct-detection receiver. This technique
      requires simpler optical components and can withstand greater link attenuation
      and splitting ratios than similar methods previously studied, making the method
      ideal for optically unamplified receivers, such as those in passive optical
      networks. We present simulations as well as experimental measurements to
      demonstrate its practicality. 

PMID- 24664048
TI  - Operation of an optically coherent frequency comb outside the metrology lab.
AB  - We demonstrate a self-referenced fiber frequency comb that can operate outside
      the well-controlled optical laboratory. The frequency comb has residual optical
      linewidths of < 1 Hz, sub-radian residual optical phase noise, and residual pulse
      to-pulse timing jitter of 2.4 - 5 fs, when locked to an optical reference. This
      fully phase-locked frequency comb has been successfully operated in a moving
      vehicle with 0.5 g peak accelerations and on a shaker table with a sustained 0.5
      g rms integrated acceleration, while retaining its optical coherence and 5-fs
      level timing jitter. This frequency comb should enable metrological measurements
      outside the laboratory with the precision and accuracy that are the hallmarks of
      comb-based systems. 

PMID- 24664049
TI  - Four-wave mixing for clock recovery of phase modulated optical OFDM superchannel.
AB  - We simulate and experimentally demonstrate a novel all-optical clock recovery
      technique for a BPSK OFDM superchannel. Four-wave mixing in SOAs is used to strip
      the modulation from the superchannel sub-carriers, two of which are filtered and
      beat together in a photodiode to recover the clock.

PMID- 24664050
TI  - Intermittent operation of QC-lasers for mid-IR spectroscopy with low heat
      dissipation: tuning characteristics and driving electronics.
AB  - Intermittent scanning for continuous-wave quantum cascade lasers is proposed
      along with a custom-built laser driver optimized for such operation. This
      approach lowers the overall heat dissipation of the laser by dropping its drive
      current to zero between individual scans and holding a longer pause between
      scans. This allows packaging cw-QCLs in TO-3 housings with built-in collimating
      optics, thus reducing cost and footprint of the device. The fully integrated,
      largely analog, yet flexible laser driver eliminates the need for any external
      electronics for current modulation, lowers the demands on power supply
      performance, and allows shaping of the tuning current in a wide range. Optimized
      ramp shape selection leads to large and nearly linear frequency tuning (>1.5 cm
      1). Experimental characterization of the proposed scheme with a QCL emitting at
      7.7 MUm gave a frequency stability of 3.2*10-5 cm-1 for the laser emission, while
      a temperature dependence of 2.3*10-4 cm-1/K was observed when the driver
      electronics was exposed to sudden temperature changes. We show that these
      characteristics make the driver suitable for high precision trace gas
      measurements by analyzing methane absorption lines in the respective spectral
      region.

PMID- 24664051
TI  - Simultaneous dual-color 3D STED microscopy.
AB  - We describe the design and implementation of a stimulated emission depletion
      (STED) microscope which allows simultaneous three-dimensional super-resolution
      imaging in two colors. A super-continuum laser source is used to provide all
      spectral bands necessary for excitation and efficient depletion to achieve a
      lateral and axial resolution of ~35 nm and ~90 nm respectively. We characterize
      the systems' performance by imaging colloidal particles and single fluorescent
      molecules. Its biological applicability is demonstrated by dual-color imaging of
      nuclear pore complexes and of DNA replication sites in mammalian cells. 

PMID- 24664052
TI  - Comparison of length measurements provided by a femtosecond optical frequency
      comb.
AB  - This paper presents a comparison of length measurements between the wavelength
      and the adjacent pulse repetition interval length (APRIL) provided by a
      femtosecond optical frequency comb. A theoretical estimation of the frequency
      stability for stabilizing the wavelength and APRIL, the frequency parameters that
      affect the stability of the APRIL in air, and the ambiguity in the length
      measurement by the APRIL are investigated. We find that the APRIL can be used as
      a low-cost measurement for the absolute length over a range of hundreds of meters
      in laboratory conditions. 

PMID- 24664053
TI  - Variable-wavelength second harmonic generation of CW Yb-fibre laser in partially
      coupled enhancement cavity.
AB  - This work for the first time proposes and studies a method of frequency doubling
      of CW non-single-frequency fibre lasers with a high-Q resonator partially coupled
      to the fibre laser cavity. The proposed new approach resulted in the following
      parameters: laser's maximal output power 880 mW at 536 nm when pumped with 6.2 W
      at 976 nm, wavelength tuneability range 521-545 nm with the output power at the
      extreme ends of this range 420 and 220 mW correspondingly. The proposed
      configuration allows efficient non-linear transformation of both CW and pulsed
      radiation in a partially coupled enhancement cavity.

PMID- 24664054
TI  - Compact Cr:ZnS channel waveguide laser operating at 2,333 nm.
AB  - A compact mid-infrared channel waveguide laser is demonstrated in Cr:ZnS with a
      view to power scaling chromium laser technology utilizing the thermo-mechanical
      advantages of Cr:ZnS over alternative transition metal doped II-VI semiconductor
      laser materials. The laser provided a maximum power of 101 mW of CW output at
      2333 nm limited only by the available pump power. A maximum slope efficiency of
      20% was demonstrated.

PMID- 24664055
TI  - Time-gated ballistic imaging using a large aperture switching beam.
AB  - Ballistic imaging commonly denotes the formation of line-of-sight shadowgraphs
      through turbid media by suppression of multiply scattered photons. The technique
      relies on a femtosecond laser acting as light source for the images and as switch
      for an optical Kerr gate that separates ballistic photons from multiply scattered
      ones. The achievable image resolution is one major limitation for the
      investigation of small objects. In this study, practical influences on the
      optical Kerr gate and image quality are discussed theoretically and
      experimentally applying a switching beam with large aperture (D = 19 mm). It is
      shown how switching pulse energy and synchronization of switching and imaging
      pulse in the Kerr cell influence the gate's transmission. Image quality of
      ballistic imaging and standard shadowgraphy is evaluated and compared, showing
      that the present ballistic imaging setup is advantageous for optical densities in
      the range of 8 < OD < 13. Owing to the spatial transmission characteristics of
      the optical Kerr gate, a rectangular aperture stop is formed, which leads to
      different resolution limits for vertical and horizontal structures in the object.
      Furthermore, it is reported how to convert the ballistic imaging setup into a
      schlieren-type system with an optical schlieren edge.

PMID- 24664056
TI  - Gain-shift induced by dopant concentration ratio in a Thulium-Bismuth doped fiber
      amplifier.
AB  - This paper details the effect of Thulium and Bismuth concentration ratio on gain
      shift at 1800 nm and 1400 nm band in a Thulium-Bismuth Doped Fiber Amplifier
      (TBDFA). The effect of Thulium and Bismuth's concentration ratio on gain shifting
      is experimentally established and subsequently numerically modeled. The analysis
      is carried out via the cross relaxation and energy transfer processes between the
      two dopants. The energy transfer in this process was studied through experimental
      and numerical analysis of three samples with different Tm/Bi concentration ratio
      of 2, 0.5 and 0.2, respectively. The optimized length for the three samples
      (TBDFA-1, TBDFA-2 and TBDFA-3) was determined and set at 6.5, 4 and 5.5 m,
      respectively. In addition, the experimental result of Thulium Doped Fiber
      Amplifier (TDFA) was compared with the earlier TBDFA samples. The gain for TBDFA
      1, with the highest Tm/Bi ratio, showed no shift at the 1800 nm region, while
      TBDFA-2 and TBDFA-3, possessing a lower Tm/Bi concentration ratio, shifted to the
      region of 1950 and 1960 nm, respectively. The gain shifting from 1460 nm to 1490
      nm is also observed. The numerical model demonstrates that the common 3F4 layer
      for 1460 nm emission (3H4->3F4), and 1800 nm emission (3F4->3H6)inversely affects
      the 1460 nm and 1800 nm gain shifting.

PMID- 24664057
TI  - When can temporally focused excitation be axially shifted by dispersion?
AB  - Temporal focusing (TF) allows for axially confined wide-field multi-photon
      excitation at the temporal focal plane. For temporally focused Gaussian beams, it
      was shown both theoretically and experimentally that the temporal focus plane can
      be shifted by applying a quadratic spectral phase to the incident beam. However,
      the case for more complex wave-fronts is quite different. Here we study the
      temporal focus plane shift (TFS) for a broader class of excitation profiles, with
      particular emphasis on the case of temporally focused computer generated
      holography (CGH) which allows for generation of arbitrary, yet speckled, 2D
      patterns. We present an analytical, numerical and experimental study of this
      phenomenon. The TFS is found to depend mainly on the autocorrelation of the CGH
      pattern in the direction of the beam dispersion after the grating in the TF
      setup. This provides a pathway for 3D control of multi-photon excitation
      patterns. 

PMID- 24664058
TI  - A novel fast phase correlation algorithm for peak wavelength detection of Fiber
      Bragg Grating sensors.
AB  - Fiber Bragg Gratings (FBGs) can be used as sensors for strain, temperature and
      pressure measurements. For this purpose, the ability to determine the Bragg peak
      wavelength with adequate wavelength resolution and accuracy is essential.
      However, conventional peak detection techniques, such as the maximum detection
      algorithm, can yield inaccurate and imprecise results, especially when the Signal
      to Noise Ratio (SNR) and the wavelength resolution are poor. Other techniques,
      such as the cross-correlation demodulation algorithm are more precise and
      accurate but require a considerable higher computational effort. To overcome
      these problems, we developed a novel fast phase correlation (FPC) peak detection
      algorithm, which computes the wavelength shift in the reflected spectrum of a FBG
      sensor. This paper analyzes the performance of the FPC algorithm for different
      values of the SNR and wavelength resolution. Using simulations and experiments,
      we compared the FPC with the maximum detection and cross-correlation algorithms.
      The FPC method demonstrated a detection precision and accuracy comparable with
      those of cross-correlation demodulation and considerably higher than those
      obtained with the maximum detection technique. Additionally, FPC showed to be
      about 50 times faster than the cross-correlation. It is therefore a promising
      tool for future implementation in real-time systems or in embedded hardware
      intended for FBG sensor interrogation. 

PMID- 24664059
TI  - High-energy pulsed Raman fiber laser for biological tissue coagulation.
AB  - We demonstrate a high-energy pulsed Raman fiber laser (RFL) with an emission
      wavelength of 1.44 MUm, corresponding to an absorption peak of water. Microsecond
      pulses with >20 mJ/pulse and >40 W peak power were generated, well above the
      threshold for tissue coagulation and ablation. Here, we focus on the optical
      characterization and optimization of high-energy and high-power RFLs excited by
      an ytterbium fiber laser, comparing three configurations that use different Raman
      gain fibers, but all of which were prepared with a one-side opened, free-run mode
      without output mirrors. We show that the free-run configuration can generate
      sufficiently high energy without requiring a closed cavity design. Experimental
      RFL characteristics corresponded well with numerical simulations. We discuss the
      Stokes beam generation process in our system and loss mechanisms mainly
      associated with fiber Bragg gratings.

PMID- 24664060
TI  - Generation of nonparaxial accelerating fields through mirrors. I: two dimensions.
AB  - Accelerating beams are wave packets that preserve their shape while propagating
      along curved trajectories. Recent constructions of nonparaxial accelerating beams
      cannot span more than a semicircle. Here, we present a ray based analysis for
      nonparaxial accelerating fields and pulses in two dimensions. We also develop a
      simple geometric procedure for finding mirror shapes that convert collimated
      fields or fields emanating from a point source into accelerating fields tracing
      circular caustics that extend well beyond a semicircle.

PMID- 24664061
TI  - Adaptive compressive ghost imaging based on wavelet trees and sparse
      representation.
AB  - Compressed sensing is a theory which can reconstruct an image almost perfectly
      with only a few measurements by finding its sparsest representation. However, the
      computation time consumed for large images may be a few hours or more. In this
      work, we both theoretically and experimentally demonstrate a method that combines
      the advantages of both adaptive computational ghost imaging and compressed
      sensing, which we call adaptive compressive ghost imaging, whereby both the
      reconstruction time and measurements required for any image size can be
      significantly reduced. The technique can be used to improve the performance of
      all computational ghost imaging protocols, especially when measuring ultra-weak
      or noisy signals, and can be extended to imaging applications at any wavelength. 

PMID- 24664062
TI  - Quasi-phase-matching of only even-order high harmonics.
AB  - High harmonic spectrum of a quasi-monochromatic pump that interacts with
      isotropic media consists of only odd-order harmonics. Addition of a secondary
      pump, e.g. a static field or the second harmonic of the primary pump, can results
      with generation of both odd and even harmonics of the primary pump. We propose a
      method for quasi-phase matching of only the even-order harmonics of the primary
      pump. We formulate a theory for this process and demonstrate it numerically. We
      also show that it leads to attosecond pulse trains with constant carrier envelop
      phase and high repetition rate. 

PMID- 24664063
TI  - Widely tunable, narrow bandwidth polycrystalline ceramic Er:YAG laser with a
      volume Bragg grating.
AB  - We report on a tunable polycrystalline ceramic Er:YAG laser with a total tuning
      range of 23.1 nm by using a volume Bragg grating. The whole tuning range was
      composed of three parts, 1614.2 nm - 1621.5 nm, 1629.3 nm - 1635.1 nm and 1639.2
      nm - 1649.2 nm. The bandwidth of the output spectrum (FWHM) of the tunable Er:YAG
      laser was narrowed down to <0.05 nm over the whole tuning range. To our
      knowledge, this is the widest tuning range so far in this material and it is the
      first time to report an Er:YAG laser operating at around 1630 nm. In the tuning
      range of 1629.3 nm- 1635.1 nm, the maximum output power of 1.4 W was obtained at
      1633.0 nm with a slope efficiency of 20.9% with respect to the incident power. 

PMID- 24664064
TI  - Interactions of Airy beams, nonlinear accelerating beams, and induced solitons in
      Kerr and saturable nonlinear media.
AB  - We investigate numerically interactions between two in-phase or out-of-phase Airy
      beams and nonlinear accelerating beams in Kerr and saturable nonlinear media in
      one transverse dimension. We discuss different cases in which the beams with
      different intensities are launched into the medium, but accelerate in opposite
      directions. Since both the Airy beams and nonlinear accelerating beams possess
      infinite oscillating tails, we discuss interactions between truncated beams, with
      finite energies. During interactions we see solitons and soliton pairs generated
      that are not accelerating. In general, the higher the intensities of interacting
      beams, the easier to form solitons; when the intensities are small enough, no
      solitons are generated. Upon adjusting the interval between the launched beams,
      their interaction exhibits different properties. If the interval is large
      relative to the width of the first lobes, the generated soliton pairs just
      propagate individually and do not interact much. However, if the interval is
      comparable to the widths of the maximum lobes, the pairs strongly interact and
      display varied behavior.

PMID- 24664065
TI  - Long distance active hyperspectral sensing using high-power near-infrared
      supercontinuum light source.
AB  - A hyperspectral remote sensing instrument employing a novel near-infrared
      supercontinuum light source has been developed for active illumination and
      identification of targets. The supercontinuum is generated in a standard normal
      dispersion multi-mode fiber and has 16 W total optical output power covering 1000
      nm to 2300 nm spectral range. A commercial 256-channel infrared spectrometer was
      used for broadband infrared detection. The feasibility of the presented
      hyperspectral measurement approach was investigated both indoors and in the
      field. Reflection spectra from several diffusive targets were successfully
      measured and a measurement range of 1.5 km was demonstrated. 

PMID- 24664066
TI  - Compact and stable THz vector spectroscopy using silicon photonics technology.
AB  - We present a compact and stable terahertz (THz) vector spectroscopy system using
      silicon photonics technology. A silicon-based integrated phase control circuit
      greatly reduces the physical size of the continuous-wave THz spectroscopy system
      and enhances environmental phase stability. Differential lightwave phase control
      using two carrier-injection electro-optic modulators enables fast and linear
      phase sweeps of THz-waves. Using the silicon-photonic circuit, we demonstrate a
      THz vector spectrometer; the dynamic ranges are 65 and 35 dB at 300 GHz and 1 THz
      with 1-ms integration time and phase variation is less than +/- 10 degrees 
      without thermal packaging.

PMID- 24664067
TI  - Pulsed operation of a resonantly pumped, linearly polarised, large mode area
      holmium-doped fibre amplifier.
AB  - We present the design of a polarisation maintaining, resonantly and cladding
      pumped, large mode area holmium-doped fibre. We describe the operation of this
      fibre in a pulsed amplifier configuration. The amplifier produced pulses with
      energy of 2.25 mJ and duration of 20 ns at a repetition rate of 20 kHz and
      average power of 45 W. The holmium-doped fibre provided >10 dB of gain at 2.09 um
      and the polarisation extinction ratio was >11.5 dB. The beam quality of the
      output (M2) was 1.6. To the best of our knowledge this is the highest pulse
      energy achieved from any singly holmium-doped fibre by an order of magnitude.

PMID- 24664068
TI  - Simulation study on light propagation in an isotropic turbulence field of the
      mixed layer.
AB  - Water tank experiments and numerical simulations are employed to investigate the
      characteristics of light propagation in the convective boundary layer (CBL). The
      CBL, namely the mixed layer (ML), was simulated in the water tank. A laser beam
      was set to horizontally go through the water tank, and the image of two
      dimensional (2D) light intensity fluctuation formed on the receiving plate
      perpendicular to the light path was recorded by CCD. The spatial spectra of both
      horizontal and vertical light intensity fluctuations were analyzed, and the
      vertical distribution profile of the scintillation index (SI) in the ML was
      obtained. The experimental results indicate that 2D light intensity fluctuation
      was isotropically distributed in the cross section perpendicular to the light
      beam in the ML. Based on the measured temperature fluctuations along the light
      path at different heights, together with the relationship between temperature and
      refractive index, the refractive index fluctuation spectra and the corresponding
      turbulence parameters were derived. The obtained parameters were applied in a
      numerical model to simulate light propagation in the isotropic turbulence field.
      The calculated results successfully reproduce the characteristics of light
      intensity fluctuation observed in the experiments. 

PMID- 24664069
TI  - Frequency stabilization of a 369 nm diode laser by nonlinear spectroscopy of
      Ytterbium ions in a discharge.
AB  - We demonstrate stabilization of an ultraviolet diode laser via Doppler-free
      spectroscopy of Ytterbium ions in a discharge. Our technique employs polarization
      spectroscopy, which produces a natural dispersive lineshape whose zero-crossing
      is largely immune to environmental drifts, making this signal an ideal absolute
      frequency reference for Yb+ ion trapping experiments. We stabilize an external
      cavity diode laser near 369 nm for cooling Yb+ ions, using amplitude modulated
      polarization spectroscopy and a commercial PID feedback system. We achieve
      stable, low-drift locking with a standard deviation of measured laser frequency ~
      400 kHz over 10 minutes, limited by the instantaneous linewidth of the diode
      laser. These results and the simplicity of our optical setup makes our approach
      attractive for stabilization of laser sources in atomic physics applications.

PMID- 24664070
TI  - Strong optical injection and the differential gain in a quantum dash laser.
AB  - By optically injecting a quantum dash laser and simultaneously producing a
      significant lowering of the device threshold, a large enhancement in the
      differential gain is realized. This effect is observed by way of a dramatic
      reduction in the linewidth enhancement factor and a large increase in the 3-dB
      modulation bandwidth, especially as the injection wavelength is blue-shifted.
      Compared to its free-running value, a 50X improvement in the laser's differential
      gain is found. 

PMID- 24664071
TI  - Polymeric slot waveguide interferometer for sensor applications.
AB  - A refractive index sensor based on slot waveguide Young interferometer was
      developed in this work. The interferometer was fabricated on a polymer platform
      and operates at a visible wavelength of 633 nm. The phase shift of the
      interference pattern was measured with various concentrations of glucose-water
      solutions, utilizing both TE and TM polarization states. The sensor was
      experimentally observed to detect a refractive index difference of 6.4 * 10(-6)
      RIU. Furthermore, the slot Young interferometer was found to compensate for
      temperature variations. The results of this work demonstrate that high
      performance sensing capability can be obtained with a polymeric slot Young
      interferometer, which can be fabricated by a simple molding process.

PMID- 24664072
TI  - Power pre-emphasis for suppression of FWM in coherent optical OFDM transmission.
AB  - Four-wave-mixing (FWM) due to the fiber nonlinearity is a major limiting factor
      in coherent optical OFDM transmission. We propose to apply power pre-emphasis,
      i.e. to allocate the transmitted power non-uniformly among subcarriers in order
      to suppress the FWM impairment. The proposed technique was numerically
      investigated for both single channel 15.6 Gbs CO-OFDM transmissions and 7-channel
      WDM transmissions, showing that up to 1 dB improvement in the system's Q-factor
      can be achieved without considering sophisticated power loading algorithms
      developed for wireless communications.

PMID- 24664073
TI  - Molybdenum disulfide (MoS2) as a broadband saturable absorber for ultra-fast
      photonics.
AB  - The nonlinear optical property of few-layered MoS2 nanoplatelets synthesized by
      the hydrothermal exfoliation method was investigated from the visible to the near
      infrared band using lasers. Both open-aperture Z-scan and balanced-detector
      measurement techniques were used to demonstrate the broadband saturable
      absorption property of few-layered MoS2. To explore its potential applications in
      ultrafast photonics, we fabricated a passive mode locker for ytterbium-doped
      fibre laser by depositing few-layered MoS2 onto the end facet of optical fiber by
      means of an optical trapping approach. Our laser experiment shows that few-layer
      MoS2-based mode locker allows for the generation of stable mode-locked laser
      pulse, centered at 1054.3 nm, with a 3-dB spectral bandwidth of 2.7 nm and a
      pulse duration of 800 ps. Our finding suggests that few-layered MoS2
      nanoplatelets can be useful nonlinear optical material for laser photonics
      devices, such as passive laser mode locker, Q-switcher, optical limiter, optical
      switcher and so on.

PMID- 24664074
TI  - Fringe-field carrier-depletion modulators with high modulation efficiency and low
      free carrier absorption.
AB  - A high-speed carrier-depletion silicon modulator based on a fringe field pn
      junction design is presented. Due to the strong fringe field, the size of heavily
      doped regions can be reduced and away from the waveguide core, whereas large
      modulation efficiency is still accomplishable. The VpiL is 1.8 V-cm and the phase
      shifter loss is 1.3 dB/mm. The figure of merit (FOM), defined by the product of
      VpiL and phase shifter loss, is estimated to be 23.4 dB-V. The modulation speed
      and depth are 11.8 GHz and 8.1 dB, respectively, which is mainly limited by the
      mobility of poly-Si.

PMID- 24664075
TI  - System performance enhancement with pre-distorted OOFDM signal waveforms in DM/DD
      systems.
AB  - In this work we propose a pre-distortion technique for the mitigation of the
      nonlinear distortion present in directly modulated/detected OOFDM systems and
      explore the system performance achieved under varying system parameters.
      Simulation results show that the proposed pre-distortion technique efficiently
      mitigates the nonlinear distortion, achieving transmission information rates
      around 40 Gbits/s and 18.5 Gbits/s over 40 km and 100 km of single mode fiber
      links, respectively, under optimum operating conditions. Moreover, the proposed
      pre-distortion technique can potentially provide higher system performance to
      that obtained with nonlinear equalization at the receiver.

PMID- 24664076
TI  - Graphene mode-locked Cr:ZnS chirped-pulse oscillator.
AB  - We report the first to our knowledge high-energy graphene mode-locked solid-state
      laser operating in the positive dispersion regime. Pulses with 15.5 nJ energy and
      42 nm spectral bandwidth with 0.87 ps duration were obtained at 2.4 MUm
      wavelength. The output can be compressed down to 189 fs. The graphene absorber
      damage threshold was established at fluence approaching 1 mJ/cm2.

PMID- 24664077
TI  - The partial space qualification of a vertically aligned carbon nanotube coating
      on aluminium substrates for EO applications.
AB  - The fabrication of NanoTube Black, a Vertically Aligned carbon NanoTube Array
      (VANTA) on aluminium substrates is reported for the first time. The coating on
      aluminium was realised using a process that employs top down thermal radiation to
      assist growth, enabling deposition at temperatures below the substrate's melting
      point. The NanoTube Black coatings were shown to exhibit directional
      hemispherical reflectance values of typically less than 1% across wavelengths in
      the 2.5 um to 15 um range. VANTA-coated aluminium substrates were subjected to
      space qualification testing (mass loss, outgassing, shock, vibration and
      temperature cycling) before their optical properties were re-assessed. Within
      measurement uncertainty, no changes to hemispherical reflectance were detected,
      confirming that NanoTube Black coatings on aluminium are good candidates for
      Earth Observation (EO) applications.

PMID- 24664078
TI  - Nanosecond colloidal quantum dot lasers for sensing.
AB  - Low-threshold, gain switched colloidal quantum dot (CQD) distributed-feedback
      lasers operating in the nanosecond regime are reported and proposed for sensing
      applications for the first time to the authors' knowledge. The lasers are based
      on a mechanically-flexible polymeric, second order grating structure overcoated
      with a thin-film of CQD/PMMA composite. The threshold fluence of the resulting
      lasers is as low as 0.5 mJ/cm2 for a 610 nm emission and the typical linewidth is
      below 0.3 nm. The emission wavelength of the lasers can be set at the design
      stage and laser operation between 605 nm and 616 nm, while using the exact same
      CQD gain material, is shown. In addition, the potential of such CQD lasers for
      refractive index sensing in solution is demonstrated by immersion in water.

PMID- 24664079
TI  - Effect of vector asymmetry of radially polarized beams in solid immersion
      microscopy.
AB  - We theoretically and experimentally investigate the effect of imperfect vector
      symmetry on radially polarized beams focused by an aplanatic solid immersion lens
      at a numerical aperture of 3.3. We experimentally achieve circularly symmetric
      focused spot with a full-width-half-maximum of ~lambda0/5.7 at lambda0 = 1,310
      nm, free-space wavelength. The tight spatial confinement and overall circular
      symmetry of the focused radially polarized beam are found to be sensitive to
      perturbations of its cylindrical polarization symmetry. The addition of a liquid
      crystal based variable retarder to the optical path can effectively ensure the
      vector symmetry and achieve circularly symmetric focused spots at such high
      numerical aperture conditions.

PMID- 24664080
TI  - Polarimetric multi-mode tilted fiber grating sensors.
AB  - The polarimetric sensing characteristics of multi-mode-fiber based tilted fiber
      Bragg gratings (MMF-TFBG) have been analyzed and experimentally demonstrated. The
      larger diameter fiber core and graded index core/cladding profile enable the
      tilted gratings to excite multiple high-order core modes with significantly
      different polarization dependence and to form a well-defined "comb" of spectrally
      separated resonances at different wavelengths. Orientation-recognized
      twist/rotation measurements (-90 degrees  to 90 degrees ) have been achieved with
      sensitivity of 0.075 dB/deg by using intensity monitoring of two orthogonally
      polarized odd core-modes (LP11 and LP12). The proposed sensor is compact, works
      in reflection (a short section of MMF-TFBG spliced with a leading-in single mode
      fiber without any offset or tapering), is insensitive to temperature (intensity
      detection instead of wavelength monitoring) and is immune to unwanted intensity
      fluctuations (differential intensity measurement). Other TFBG sensing modalities,
      such as lateral pressure and surrounding refractive index are demonstrated
      separately with the same device configuration and interrogation principles.

PMID- 24664081
TI  - Near-perfect absorption in epsilon-near-zero structures with hyperbolic
      dispersion.
AB  - We investigate the interaction of polarized electromagnetic waves with hyperbolic
      metamaterial structures, whereby the in-plane permittivity component epsilonx is
      opposite in sign to the normal component epsilonz. We find that when the
      thickness of the metamaterial is smaller than the wavelength of the incident
      wave, hyperbolic metamaterials can absorb significantly higher amounts of
      electromagnetic energy compared to their conventional counterparts. We also
      demonstrate that for wavelengths leading to R(epsilonz) ~ 0, near-perfect
      absorption arises and persists over a range of frequencies and subwavelength
      structure thicknesses.

PMID- 24664082
TI  - A novel double-image encryption scheme based on cross-image pixel scrambling in
      gyrator domains.
AB  - Recently, a number of double-image cryptosystems have been developed. However,
      there are notable security performance differences between the two encryption
      channels in these algorithms. This weakness downgrades the security level and
      practicability of these cryptosystems, as the cryptosystems cannot guarantee all
      the input images be transmitted in the channel with higher security level. In
      this paper, we propose a novel double-image encryption scheme based on cross
      image pixel scrambling in gyrator domains. The two input images are firstly
      shuffled by the proposed cross-image pixel scrambling approach, which can well
      balance the pixel distribution across the input images. The two scrambled images
      will be encoded into the real and imaginary parts of a complex function, and then
      converted into gyrator domains. An iterative architecture is designed to enhance
      the security level of the cryptosystem, and the cross-image pixel scrambling
      operation is performed to the real and imaginary parts of the generated complex
      encrypted data in each round. Numerical simulation results prove that a
      satisfactory and balanced security performance can be achieved in both channels.

PMID- 24664083
TI  - Introduction to the issue on Physics and Applications of Laser Dynamics (IS-PALD
      2013).
AB  - We introduce the Optics Express special issue of the 3rd symposium on Physics and
      Applications of Laser Dynamics (IS-PALD). This issue consists of expanded papers
      related to oral and poster presentations. Selected papers represent the best of
      IS-PALD 2013. 

PMID- 24664084
TI  - Intraperitoneal development of the filarial nematode Brugia malayi in the
      Mongolian jird (Meriones unguiculatus).
AB  - In the present study, we describe intraperitoneal development of the FR3 strain
      of Brugia malayi in Mongolian jirds (Meriones unguiculatus). The third molt for
      male worms occurred between 4 and 7 days postinfection (dpi) and between 4 and 8
      dpi for females. The fourth and final molt occurred between days 21 and 29 for
      males and 25 and 34 for females, considerably earlier than the times reported for
      subcutaneous infection models using cats and jirds. The timing of the third molt
      coincided largely with reports for subcutaneous Brugia pahangi infections of cats
      and jirds, but the final molt occurred considerably later and lasted longer than
      those reported for subcutaneous B. pahangi models. Spermatogenesis occurred by at
      least 50 dpi in adult males, and insemination of females likely occurred between
      50 and 60 dpi. Microfilariae were observed in the uteri and ovejectors of adult
      females at 65 dpi.

PMID- 24664086
TI  - Electrochemical modulation of SERS at the liquid/liquid interface.
AB  - A surface enhanced Raman scattering system to detect silver nanoparticle
      adsorption at the water|1,2-dichlorobenzene interface is reported. The Raman
      response as a function of distance on either side of the interface reveals a
      reproducible spatial variation, which is potential dependent for a number of
      adsorption and desorption cycles. 

PMID- 24664085
TI  - Apraxia and motor dysfunction in corticobasal syndrome.
AB  - BACKGROUND: Corticobasal syndrome (CBS) is characterized by multifaceted motor
      system dysfunction and cognitive disturbance; distinctive clinical features
      include limb apraxia and visuospatial dysfunction. Transcranial magnetic
      stimulation (TMS) has been used to study motor system dysfunction in CBS, but the
      relationship of TMS parameters to clinical features has not been studied. The
      present study explored several hypotheses; firstly, that limb apraxia may be
      partly due to visuospatial impairment in CBS. Secondly, that motor system
      dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is
      linked to limb apraxia. Finally, that atrophy of the primary motor cortex,
      studied using voxel-based morphometry analysis (VBM), is associated with motor
      system dysfunction and limb apraxia in CBS. METHODS: Imitation of meaningful and
      meaningless hand gestures was graded to assess limb apraxia, while cognitive
      performance was assessed using the Addenbrooke's Cognitive Examination - Revised
      (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients
      underwent TMS, to assess cortical function, and VBM. RESULTS: In total, 17
      patients with CBS (7 male, 10 female; mean age 64.4+/- 6.6 years) were studied
      and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a
      relatively inexcitable motor cortex, with evidence of cortical dysfunction in the
      remaining 76.5% patients. Reduced resting motor threshold, and visuospatial
      performance, correlated with limb apraxia. Patients with a resting motor
      threshold <50% performed significantly worse on the visuospatial sub-task of the
      ACE-R than other CBS patients. Cortical function correlated with atrophy of the
      primary and pre-motor cortices, and the thalamus, while apraxia correlated with
      atrophy of the pre-motor and parietal cortices. CONCLUSIONS: Cortical dysfunction
      appears to underlie the core clinical features of CBS, and is associated with
      atrophy of the primary motor and pre-motor cortices, as well as the thalamus,
      while apraxia correlates with pre-motor and parietal atrophy.

PMID- 24664088
TI  - Fetal onset ventriculomegaly and subependymal cysts in a pyridoxine dependent
      epilepsy patient.
AB  - Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene
      encoding alpha-aminoadipic semialdehyde dehydrogenase. The classic clinical
      presentation is neonatal seizures responsive only to pyridoxine therapy. White
      matter abnormalities, corpus callosum agenesis or hypoplasia, megacisterna magna,
      cortical dysplasia, neuronal heterotopias, intracerebral hemorrhage, and
      hydrocephalus in neuroimaging have been reported in patients with PDE. We report
      a new patient with asymmetric progressive ventriculomegaly noted on fetal
      sonography at 22 weeks' gestation. Postnatal brain sonography on day 1 and MRI on
      day 5 confirmed bilateral asymmetric ventriculomegaly caused by bilateral
      subependymal cysts. Intractable seizures at age 7 days initially responded to
      phenobarbital. Markedly elevated urinary alpha-aminoadipic acid semialdehyde
      levels and compound heterozygous mutations in the ALDH7A1 gene
      (c.446C>A/c.919C>T) confirmed the diagnosis of PDE caused by ALDH7A1 genetic
      defect. Despite the presence of structural brain malformations and subependymal
      cysts, PDE should always be included in the differential diagnosis of neonatal
      seizures that are refractory to treatment with antiepileptic drugs. 

PMID- 24664089
TI  - Developing health care clinic partnerships in resource-limited regions.

PMID- 24664087
TI  - Short-term neural adaptation to simultaneous bifocal images.
AB  - Simultaneous vision is an increasingly used solution for the correction of
      presbyopia (the age-related loss of ability to focus near images). Simultaneous
      Vision corrections, normally delivered in the form of contact or intraocular
      lenses, project on the patient's retina a focused image for near vision
      superimposed with a degraded image for far vision, or a focused image for far
      vision superimposed with the defocused image of the near scene. It is expected
      that patients with these corrections are able to adapt to the complex
      Simultaneous Vision retinal images, although the mechanisms or the extent to
      which this happens is not known. We studied the neural adaptation to simultaneous
      vision by studying changes in the Natural Perceived Focus and in the Perceptual
      Score of image quality in subjects after exposure to Simultaneous Vision. We show
      that Natural Perceived Focus shifts after a brief period of adaptation to a
      Simultaneous Vision blur, similar to adaptation to Pure Defocus. This shift
      strongly correlates with the magnitude and proportion of defocus in the adapting
      image. The magnitude of defocus affects perceived quality of Simultaneous Vision
      images, with 0.5 D defocus scored lowest and beyond 1.5 D scored "sharp".
      Adaptation to Simultaneous Vision shifts the Perceptual Score of these images
      towards higher rankings. Larger improvements occurred when testing simultaneous
      images with the same magnitude of defocus as the adapting images, indicating that
      wearing a particular bifocal correction improves the perception of images
      provided by that correction. 

PMID- 24664090
TI  - Renal cortical abnormalities in siblings of index patients with vesicoureteral
      reflux.
AB  - OBJECTIVE: Screening siblings of index patients with vesicoureteral reflux (VUR)
      has been proposed to identify children who are at risk for renal damage. However,
      screening siblings for VUR remains controversial. We investigated the prevalence
      of VUR and renal cortical abnormalities in the sibling population in a large
      cohort of families with VUR. METHODS: Between 1998 and 2012, parents of index
      patients with grade III to V VUR were asked permission to screen siblings <6
      years of age for VUR. Siblings were divided into 2 groups: siblings with a
      documented history of a previous urinary tract infection (UTI) and siblings who
      were screened for VUR and never had a UTI. A logistic regression model was used
      to determine independent risk factors associated with renal cortical
      abnormalities such as history of presentation, age, gender, and grade of VUR.
      RESULTS: There were 318 siblings in 275 families in the study. VUR was found
      after screening in 190 (60%) siblings and after a UTI in 128 (40%). Multivariate
      analysis revealed that siblings who had a previous UTI (odds ratio: 3.38),
      siblings with high grade reflux (odds ratio: 3.62), and siblings over 1 year of
      age (odds ratio: 2.84) were the most significant independent risk factors
      associated with renal cortical abnormalities. CONCLUSIONS: There is increased
      risk of renal cortical abnormalities in siblings with a previous UTI, siblings
      with high-grade VUR, and siblings over age 1 year. This information may help to
      counsel parents about the risk of VUR and reflux nephropathy in familial VUR.

PMID- 24664091
TI  - Avoidable hospitalizations in youth with kidney failure after transfer to or with
      only adult care.
AB  - OBJECTIVE: Hospital admissions for ambulatory care-sensitive conditions (also
      called avoidable hospitalizations) are a measure of quality and access to
      outpatient care. We determined if young patients with end-stage renal disease
      (ESRD) are at increased risk of avoidable hospitalizations. METHODS: A national
      organ failure registry was used to identify patients with ESRD onset at <22 years
      of age between April 1, 2001, and March 31, 2010, who had received care in an
      adult care facility after age 15 years. The cohort was linked to the national
      hospitalizations database to identify avoidable hospitalizations relevant for
      young patients with ESRD. Patients were followed up until death, loss to follow
      up, or study end. Two groups were studied: (1) patients transferred from
      pediatric to adult care; and (2) patients receiving ESRD care exclusively in
      adult centers. We determined the association between overall and avoidable
      hospitalization rates and both age and transfer status by using Poisson
      regression models. RESULTS: Our cohort included 349 patients. Among the 92
      (26.4%) patients transferred to adult care during the study period, avoidable
      hospitalization rates were highest during the period 3 to <4 years after transfer
      (rate ratio: 3.19 [95% confidence interval: 1.42-7.18]) compared with the last
      year in pediatric care. Among the 257 (73.6%) patients who received ESRD care
      exclusively in adult centers, avoidable hospitalization rates increased with age.
      CONCLUSIONS: Among those who were transferred to adult care, avoidable
      hospitalization rates increased after transfer. Avoidable hospitalization rates
      increased with age in ESRD patients who received care in adult centers. Young
      patients with ESRD are at increased risk of avoidable hospitalizations.

PMID- 24664092
TI  - Ceftriaxone and acute renal failure in children.
AB  - OBJECTIVE: Our aim was to evaluate the clinical profile, treatment, and outcome
      of ceftriaxone-associated postrenal acute renal failure (PARF) in children.
      METHODS: We retrospectively studied 31 consecutive cases from 2003 to 2012 for
      PARF after ceftriaxone treatment. There was no past history of urolithiasis or
      nephropathy in these children. RESULTS: The average time of ceftriaxone
      administration before PARF was 5.2 days. The major symptoms apart from anuria
      included flank pain (>3 years old, 25/25), excessive crying (<3 years, 6/6), and
      vomiting (19/33). Ultrasound showed mild hydronephrosis (25/31) and ureteric
      calculi (11/31). Nine children recovered after 1 to 4 days of pharmacotherapy.
      Twenty-one children who were resistant to pharmacotherapy underwent retrograde
      ureteral catheterization. After catheterization of their ureters, normal urine
      flow was observed, and the symptoms subsided immediately. Catheter insertion
      failed in 1 child who subsequently underwent 3 sessions of hemodialysis before
      normal urination was restored. Ceftriaxone was verified to be the main component
      of the calculi in 4 children by tandem mass spectrometric analysis. The recovery
      was complete in all cases. CONCLUSIONS: Ceftriaxone therapy in children may cause
      PARF. Early diagnosis and prompt pharmacological therapy are important in
      relieving the condition. Retrograde ureteral catheterization is an effective
      treatment of those who fail to respond to pharmacotherapy.

PMID- 24664094
TI  - Meta-analysis of parental protection of children from tobacco smoke exposure.
AB  - BACKGROUND AND OBJECTIVE: Worldwide, roughly 40% of children are exposed to the
      damaging and sometimes deadly effects of tobacco smoke. Interventions aimed at
      reducing child tobacco smoke exposure (TSE) have shown mixed results. The
      objective of this study was to perform a systematic review and meta-analysis to
      quantify effects of interventions aimed at decreasing child TSE. METHODS: Data
      sources included Medline, PubMed, Web of Science, PsycNet, and Embase. Controlled
      trials that included parents of young children were selected. Two reviewers
      extracted TSE data, as assessed by parentally-reported exposure or protection
      (PREP) and biomarkers. Risk ratios and differences were calculated by using the
      DerSimonian and Laird random-effects model. Exploratory subgroup analyses were
      performed. RESULTS: Thirty studies were included. Improvements were observed from
      baseline to follow-up for parentally-reported and biomarker data in most
      intervention and control groups. Interventions demonstrated evidence of small
      benefit to intervention participants at follow-up (PREP: 17 studies, n = 6820,
      relative risk 1.12, confidence interval [CI] 1.07 to 1.18], P < .0001). Seven
      percent more children were protected in intervention groups relative to control
      groups. Intervention parents smoked fewer cigarettes around children at follow-up
      than did control parents (P = .03). Biomarkers (13 studies, n = 2601) at follow
      up suggested lower child exposure among intervention participants (RD -0.05, CI 
      0.13 to 0.03, P = .20). CONCLUSIONS: Interventions to prevent child TSE are
      moderately beneficial at the individual level. Widespread child TSE suggests
      potential for significant population impact. More research is needed to improve
      intervention effectiveness and child TSE measurement.

PMID- 24664093
TI  - Collaborative care outcomes for pediatric behavioral health problems: a cluster
      randomized trial.
AB  - OBJECTIVE: To assess the efficacy of collaborative care for behavior problems,
      attention-deficit/hyperactivity disorder (ADHD), and anxiety in pediatric primary
      care (Doctor Office Collaborative Care; DOCC). METHODS: Children and their
      caregivers participated from 8 pediatric practices that were cluster randomized
      to DOCC (n = 160) or enhanced usual care (EUC; n = 161). In DOCC, a care manager
      delivered a personalized, evidence-based intervention. EUC patients received
      psychoeducation and a facilitated specialty care referral. Care processes
      measures were collected after the 6-month intervention period. Family outcome
      measures included the Vanderbilt ADHD Diagnostic Parent Rating Scale, Parenting
      Stress Index-Short Form, Individualized Goal Attainment Ratings, and Clinical
      Global Impression-Improvement Scale. Most measures were collected at baseline,
      and 6-, 12-, and 18-month assessments. Provider outcome measures examined
      perceived treatment change, efficacy, and obstacles, and practice climate.
      RESULTS: DOCC (versus EUC) was associated with higher rates of treatment
      initiation (99.4% vs 54.2%; P < .001) and completion (76.6% vs 11.6%, P < .001),
      improvement in behavior problems, hyperactivity, and internalizing problems (P <
      .05 to .01), and parental stress (P < .05-.001), remission in behavior and
      internalizing problems (P < .01, .05), goal improvement (P < .05 to .001),
      treatment response (P < .05), and consumer satisfaction (P < .05). DOCC
      pediatricians reported greater perceived practice change, efficacy, and skill use
      to treat ADHD (P < .05 to .01). CONCLUSIONS: Implementing a collaborative care
      intervention for behavior problems in community pediatric practices is feasible
      and broadly effective, supporting the utility of integrated behavioral health
      care services.

PMID- 24664095
TI  - Psychiatric functioning and quality of life in young patients with cardiac rhythm
      devices.
AB  - BACKGROUND: Less is known about depression, anxiety and quality of life (QoL) in
      children and adolescents with pacemakers (PMs) and implantable cardioverter
      defibrillators (ICDs) than is known in adults with these devices. METHODS: A
      standardized psychiatric interview diagnosed anxiety/depressive disorders in a
      cross-sectional study. Self-report measures of anxiety, depression and post
      traumatic stress disorder were obtained. Medical disease severity, family
      functioning and QoL data were collected. A total of 166 patients were enrolled
      (52 ICD, 114 PM; median age 15 years). RESULTS: Prevalence of current and
      lifetime psychiatric disorders was higher in patients with ICDs than PMs
      (Current: 27% vs. 11%, P = .02; Lifetime: 52% ICD vs. 34% PM, P = .01). Patients
      with ICDs had more anxiety than a healthy population (25% vs. 7%, P < .01).
      Patients with ICDs and PMs had similar levels of depression as a healthy
      population (ICD 10%, PM 4%, reference 4%, P = .29). In multivariate analysis
      including a medical disease score, demographics, exposure to beta-blockers,
      activity limitations, hospitalizations, shocks and procedures, the type of device
      (PM versus ICD) did not predict psychiatric diagnoses when age at implantation
      and the severity of medical disease were controlled for. Patients with ICDs and
      PMs had lower physical QoL scores (ICD 45, PM 47.5, Norm 53, P <= .03), but
      similar psychosocial functioning scores (ICD 49, PM 51, Norm 51, P >= .16) versus
      a normal reference population. CONCLUSIONS: Anxiety is highly prevalent in young
      patients with ICDs, but the higher rates can be attributed to medical disease
      severity and age at implantation instead of type of device.

PMID- 24664096
TI  - Improving immunization rates in a hospital-based primary care practice.
AB  - OBJECTIVE: We implemented a quality improvement initiative aimed at reaching a
      95% immunization rate for patients aged 24 months. The setting was a hospital
      based pediatric primary care practice in Boston, Massachusetts. We defined
      immunization as full receipt of the vaccine series as recommended by the Centers
      for Disease Control and Prevention. METHODS: The initiative was team-based and
      structured around 3 core interventions: systematic identification and capture of
      target patients, use of a patient-tracking registry, and patient outreach and
      care coordination. We measured monthly overall and modified immunization rates
      for patients aged 24 months. The modified rate excluded vaccine refusals and
      practice transfers. We plotted monthly overall and modified immunization rates on
      statistical process control charts to monitor progress and evaluate impact.
      RESULTS: We measured immunization rates for 3298 patients aged 24 months between
      January 2009 and December 2012. Patients were 48% (n = 1576) female, 77.3% (n =
      2548) were African American or Hispanic, and 70.2% (n = 2015) were publicly
      insured. Using control charts, we established mean overall and modified
      immunization rates of 90% and 93%, respectively. After implementation, we
      observed an increase in the mean modified immunization rate to 95%. CONCLUSIONS:
      A quality improvement initiative enabled our pediatric practice to increase its
      modified immunization rate to 95% for children aged 24 months. We attribute the
      improvement to the incorporation of medical home elements including a
      multidisciplinary team, patient registry, and care coordination.

PMID- 24664097
TI  - Activity levels in mothers and their preschool children.
AB  - OBJECTIVES: To investigate the association between objectively measured maternal
      and preschool-aged children's physical activity, determine how this association
      differs by demographic and temporal factors, and identify factors associated with
      maternal activity levels. METHODS: In the UK Southampton Women's Survey, physical
      activity levels of 554 4-year-olds and their mothers were measured concurrently
      by using accelerometry for <=7 days. Two-level mixed-effects linear regression
      was used to model the association between maternal and children's minutes spent
      sedentary, in light (LPA) and moderate-to-vigorous physical activity (MVPA).
      Linear regression was used to investigate correlates of maternal activity.
      RESULTS: Mother-child daily activity levels were positively associated at all
      activity intensities (sedentary, LPA, and MVPA; all P < .001). The association
      for sedentary time was stronger for normal-weight children (versus those who were
      overweight/obese), and those attending preschool part-time (versus full-time).
      The mother-child association for LPA differed by maternal education and was
      stronger at the weekend (versus weekdays). The opposite was true for MVPA.
      Sedentary time and MVPA were most strongly associated in mornings, with LPA most
      strongly associated in the evenings. Maternal BMI, age leaving school, number and
      age of children at home, and working hours were independently associated with
      maternal daily sedentary time and LPA. CONCLUSIONS: Physical activity levels in
      mothers and their 4-year-old children are directly associated, with associations
      at different activity intensities influenced by temporal and demographic factors.
      Influences on maternal physical activity levels also differ by activity
      intensity. Providing targeted interventions for mothers of young children may
      increase both groups' activity.

PMID- 24664098
TI  - Stabbing headache in an 8-year-old girl: primary or drug induced headache?
AB  - The occurrence of stabbing headaches in children requires a thorough diagnostic
      approach that excludes secondary headaches. The organic background should be
      taken into consideration when alarming symptoms occur, such as a purely 1-sided
      location, a change in the character of the headache, or possibly a link to
      physical activity. The current study describes the case of an 8-year-old girl who
      suffered short-lasting stabbing headache attacks. The headaches with increasing
      intensity and frequency started 1 month before her hospitalization and were
      usually preceded by physical activity (dancing, running). The pain, which was
      located in the right supraorbital region, lasted 1 second and occurred several
      times during the day. No associated symptoms were observed. In addition, the girl
      suffered from allergic rhinitis and was on antiallergic treatment
      (levocetirizine, fluticasone nasal spray). On admission she was in good general
      condition, and a pediatric and neurologic examination revealed no abnormalities.
      Her brain MRI was normal. The initial diagnosis was that the patient was
      suffering from primary stabbing headaches. However, during a follow-up visit 4
      months later, a relationship was observed between the cessation of the headache
      attacks and the discontinuation of an antihistaminic drug. Six months later, the
      girl remained headache free. In cases involving differential diagnoses of
      stabbing headaches, it is important to consider the adverse reactions of the
      drugs used. 

PMID- 24664099
TI  - Group I PAK inhibitor IPA-3 induces cell death and affects cell adhesivity to
      fibronectin in human hematopoietic cells.
AB  - P21-activated kinases (PAKs) are involved in the regulation of multiple processes
      including cell proliferation, adhesion and migration. However, the current
      knowledge about their function is mainly based on results obtained in adherent
      cell types. We investigated the effect of group I PAK inhibition using the
      compound IPA-3 in a variety of human leukemic cell lines (JURL-MK1, MOLM-7, K562,
      CML-T1, HL-60, Karpas-299, Jurkat, HEL) as well as in primary blood cells. IPA-3
      induced cell death with EC50 ranging from 5 to more than 20 MUM. Similar range
      was found for IPA-3-mediated dephosphorylation of a known PAK downstream
      effector, cofilin. The cell death was associated with caspase-3 activation, PARP
      cleavage and apoptotic DNA fragmentation. In parallel, 20 MUM IPA-3 treatment
      induced rapid and marked decrease of the cell adhesivity to fibronectin. Per
      contra, partial reduction of PAK activity using lower dose IPA-3 or siRNA
      resulted in a slight increase in the cell adhesivity. The changes in the cell
      adhesivity were also studied using real-time microimpedance measurement and by
      interference reflection microscopy. Significant differences in the intracellular
      IPA-3 level among various cell lines were observed indicating that an active
      mechanism is involved in IPA-3 transport. 

PMID- 24664100
TI  - CD73 expression is dynamically regulated in the germinal center and bone marrow
      plasma cells are diminished in its absence.
AB  - CD73 catalyzes the conversion of extracellular nucleosides to adenosine,
      modulating inflammatory and T cell responses. Elevated expression of CD73 marks
      subpopulations of murine memory B cells (MBC), but its role in memory development
      or function is unknown. Here, we demonstrate that CD73 is progressively
      upregulated on germinal center (GC) B cells following immunization, is expressed
      at even higher levels among T follicular helper cells, but is absent among plasma
      cells (PC) and plasmablasts (PB). We analyzed the T-dependent B cell response in
      CD73 knockout mice (CD73KO). During the early response, CD73KO and wild type (WT)
      mice formed GCs, MBCs and splenic PBs and PCs similarly, and MBCs functioned
      similarly in the early secondary response. Late in the primary response, however,
      bone marrow (BM) PCs were markedly decreased in CD73KO animals. Tracking this
      phenotype, we found that CD73 expression was required on BM-derived cells for
      optimal BM PC responses. However, deletion of CD73 from either B or T lymphocytes
      alone did not recapitulate the phenotype. This suggests that CD73 expression is
      sufficient on either cell type, consistent with its function as an ectoenzyme.
      Together, these findings suggest that CD73-dependent adenosine signaling is
      prominent in the mature GC and required for establishment of the long-lived PC
      compartment, thus identifying a novel role for CD73 in humoral immunity. 

PMID- 24664102
TI  - Three weeks of murine hindlimb unloading induces shifts from B to T and from th
      to tc splenic lymphocytes in absence of stress and differentially reduces cell
      specific mitogenic responses.
AB  - Extended space missions are known to induce stress and immune dysregulation.
      Hindlimb unloading is a ground-based model used to reproduce most spaceflight
      conditions. The aim of this study was to better characterize the consequences of
      prolonged exposure to hindlimb unloading on murine splenic lymphocyte sub
      populations. To ensure that the observed changes were not due to tail restraint
      but to the antiorthostatic position, three groups of mice were used: control (C),
      orthostatic restrained (R) and hindlimb unloaded (HU). After 21 days of exposure,
      no difference in serum corticosterone levels nor in thymus and spleen weights
      were observed between HU mice and their counterparts, revealing a low state of
      stress. Interestingly, flow cytometric analyses showed that B cells were
      drastically reduced in HU mouse spleens by 59% and, while the T cells number did
      not change, the Th/Tc ratio was decreased. Finally, the use of a fluorescent dye
      monitoring lymphoproliferation demonstrated that lymphocyte response to mitogen
      was reduced in Th and Tc populations and to a greater extent in B cells. Thus, we
      showed for the first time that, even if restraint has its own effects on the
      animals and their splenic lymphocytes, the prolonged antiorthostatic position
      leads, despite the absence of stress, to an inversion of the B/T ratio in the
      spleen. Furthermore, the lymphoproliferative response was impaired with a strong
      impact on B cells. Altogether, these results suggest that B cells are more
      affected by hindlimb unloading than T cells which may explain the high
      susceptibility to pathogens, such as gram-negative bacteria, described in animal
      models and astronauts. 

PMID- 24664103
TI  - Identification of protein partners in mycobacteria using a single-step affinity
      purification method.
AB  - Tuberculosis is a leading cause of death in developing countries. Efforts are
      being made to both prevent its spread and improve curability rates. Understanding
      the biology of the bacteria causing the disease, Mycobacterium tuberculosis (M.
      tuberculosis), is thus vital. We have implemented improved screening methods for
      protein-protein interactions based on affinity purification followed by high
      resolution mass spectrometry. This method can be efficiently applied to both
      medium- and high-throughput studies aiming to characterize protein-protein
      interaction networks of tubercle bacilli. Of the 4 tested epitopes FLAG, enhanced
      green fluorescent protein (eGFP), protein A and haemagglutinin, the eGFP tag was
      found to be most useful on account of its easily monitored expression and its
      ability to function as a simultaneous tool for subcellular localization studies.
      It presents a relatively low background with cost-effective purification. RNA
      polymerase subunit A (RpoA) was used as a model for investigation of a large
      protein complex. When used as bait, it co-purified with all remaining RNA
      polymerase core subunits as well as many accessory proteins. The amount of RpoA
      strongly correlated with the amount of quantification peptide used as part of the
      tagging system in this study (SH), making it applicable for semi-quantification
      studies. Interactions between the components of the RpoA-eGFP protein complex
      were further confirmed using protein cross-linking. Dynamic changes in the
      composition of protein complexes under induction of UV damage were observed when
      UvrA-eGFP expressing cells treated with UV light were used to co-purify UvrA
      interaction partners. 

PMID- 24664104
TI  - A Co(II)-Ru(II) dyad relevant to light-driven water oxidation catalysis.
AB  - Artificial photosynthesis aims at efficient water splitting into hydrogen and
      oxygen, by exploiting solar light. As a priority requirement, this process
      entails the integration of suitable multi-electron catalysts with light absorbing
      units, where charge separation is generated in order to drive the catalytic
      routines. The final goal could be the transposition of such an asset into a
      photoelectrocatalytic cell, where the two half-reactions, proton reduction to
      hydrogen and water oxidation to oxygen, take place at two appropriately
      engineered photoelectrodes. We herein report a covalent approach to anchor a
      Co(II) water oxidation catalyst to a Ru(II) polypyridine photosensitizer unit;
      photophysical characterisation and the catalytic activity of such a dyad in a
      light activated cycle are reported, and implications for the development of
      regenerative systems are discussed.

PMID- 24664107
TI  - Celebrating 300 years of chemistry at Edinburgh.

PMID- 24664106
TI  - Tracking cholesterol/sphingomyelin-rich membrane domains with the ostreolysin A
      mCherry protein.
AB  - Ostreolysin A (OlyA) is an ~15-kDa protein that has been shown to bind
      selectively to membranes rich in cholesterol and sphingomyelin. In this study, we
      investigated whether OlyA fluorescently tagged at the C-terminal with mCherry
      (OlyA-mCherry) labels cholesterol/sphingomyelin domains in artificial membrane
      systems and in membranes of Madin-Darby canine kidney (MDCK) epithelial cells.
      OlyA-mCherry showed similar lipid binding characteristics to non-tagged OlyA.
      OlyA-mCherry also stained cholesterol/sphingomyelin domains in the plasma
      membranes of both fixed and living MDCK cells, and in the living cells, this
      staining was abolished by pretreatment with either methyl-beta-cyclodextrin or
      sphingomyelinase. Double labelling of MDCK cells with OlyA-mCherry and the
      sphingomyelin-specific markers equinatoxin II-Alexa488 and GST-lysenin, the
      cholera toxin B subunit as a probe that binds to the ganglioside GM1, or the
      cholesterol-specific D4 domain of perfringolysin O fused with EGFP, showed
      different patterns of binding and distribution of OlyA-mCherry in comparison with
      these other proteins. Furthermore, we show that OlyA-mCherry is internalised in
      living MDCK cells, and within 90 min it reaches the juxtanuclear region via
      caveolin-1-positive structures. No binding to membranes could be seen when OlyA
      mCherry was expressed in MDCK cells. Altogether, these data clearly indicate that
      OlyA-mCherry is a promising tool for labelling a distinct pool of
      cholesterol/sphingomyelin membrane domains in living and fixed cells, and for
      following these domains when they are apparently internalised by the cell. 

PMID- 24664108
TI  - The effect of acute exercise and psychosocial stress on fine motor skills and
      testosterone concentration in the saliva of high school students.
AB  - Little is known about the influence of different stressors on fine motor skills,
      the concentration of testosterone (T), and their interaction in adolescents.
      Therefore, 62 high school students aged 14-15 years were randomly assigned to two
      experimental groups (exercise, psychosocial stress) and a control group. Exercise
      stress was induced at 65-75% of the maximum heart rate by running for 15 minutes
      (n = 24). Psychosocial stress was generated by an intelligence test (HAWIK-IV),
      which was uncontrollable and characterized by social-evaluative-threat to the
      students (n = 21). The control group followed was part of a regular school lesson
      with the same duration (n = 28). Saliva was collected after a normal school
      lesson (pre-test) as well as after the intervention/control period (post-test)
      and was analyzed for testosterone. Fine motor skills were assessed pre- and post
      intervention using a manual dexterity test (Flower Trail) from the Movement
      Assessment Battery for Children-2. A repeated measure ANCOVA including gender as
      a covariate revealed a significant group by test interaction, indicating an
      increase in manual dexterity only for the psychosocial stress group. Correlation
      analysis of all students shows that the change of testosterone from pre- to post
      test was directly linked (r = -.31, p = .01) to the changes in manual dexterity
      performance. Participants showing high increases in testosterone from pre- to
      post-test made fewer mistakes in the fine motor skills task. Findings suggest
      that manual dexterity increases when psychosocial stress is induced and that
      improvement of manual dexterity performance corresponds with the increase of
      testosterone. 

PMID- 24664109
TI  - The relationship between waterpipe and cigarette smoking in low and middle income
      countries: cross-sectional analysis of the global adult tobacco survey.
AB  - INTRODUCTION: Waterpipe tobacco smoking is receiving growing attention due to
      accumulating evidence suggesting increasing prevalence in some populations and
      deleterious health effects. Nevertheless, the relationship between waterpipe and
      cigarette smoking remain unknown, particularly in low and middle income
      countries. MATERIALS AND METHODS: We analysed waterpipe and cigarette smoking
      using data from Global Adult Tobacco Survey, a household survey of adults aged
      >=15 years conducted between 2008-2010 in LMICs. Factors associated with
      waterpipe and cigarette use were assessed using multiple logistic regression.
      Factors associated with the quantity of waterpipe and cigarette smoking were
      assessed using log-linear regression models. RESULTS: After adjusting for age,
      gender, residence, education, occupation and smokeless tobacco use, waterpipe
      smoking was significantly higher among cigarette users than in non-cigarette
      users in India (5.6% vs. 0.6%, AOR 13.12, 95% CI 7.41-23.23) and Russia (6.7% vs.
      0.2%, AOR 27.73, 95% CI 11.41-67.43), but inversely associated in Egypt (2.6% vs.
      3.4%, AOR 0.21, 95% CI 0.15-0.30) and not associated in Vietnam (13.3% vs. 4.7%,
      AOR 0.96, 95% CI 0.74-1.23). Compared to non-cigarette smokers, waterpipe smokers
      who also used cigarettes had more waterpipe smoking sessions per week in Russia
      (1.3 vs. 2.9, beta coefficient 0.31, 95% CI 0.06, 0.57), but less in Egypt (18.2
      vs. 10.7, beta coefficient -0.45, 95% CI -0.73, -0.17) and Vietnam (102.0 vs.
      79.3, beta coefficient -0.31, 95% CI -0.56, -0.06) and similar amounts in India
      (29.4 vs. 32.6, beta coefficient -0.12, 95% CI -0.46, 0.22). CONCLUSIONS:
      Waterpipe smoking is low in most LMICs but important country-level differences in
      use, including concurrent cigarette smoking, should be taken into account when
      designing and evaluating tobacco control interventions.

PMID- 24664110
TI  - The pneumococcal polysaccharide capsule and pneumolysin differentially affect
      CXCL8 and IL-6 release from cells of the upper and lower respiratory tract.
AB  - The polysaccharide capsule and pneumolysin toxin are major virulence factors of
      the human bacterial pathogen Streptococcus pneumoniae. Colonization of the
      nasopharynx is asymptomatic but invasion of the lungs can result in invasive
      pneumonia. Here we show that the capsule suppresses the release of the pro
      inflammatory cytokines CXCL8 (IL-8) and IL-6 from the human pharyngeal epithelial
      cell line Detroit 562. Release of both cytokines was much less from human
      bronchial epithelial cells (iHBEC) but levels were also affected by capsule.
      Pneumolysin stimulates CXCL8 release from both cell lines. Suppression of CXCL8
      homologue (CXCL2/MIP-2) release by the capsule was also observed in vivo during
      intranasal colonization of mice but was only discernable in the absence of
      pneumolysin. When pneumococci were administered intranasally to mice in a model
      of long term, stable nasopharyngeal carriage, encapsulated S. pneumoniae remained
      in the nasopharynx whereas the nonencapsulated pneumococci disseminated into the
      lungs. Pneumococcal capsule plays a role not only in protection from phagocytosis
      but also in modulation of the pro-inflammatory immune response in the respiratory
      tract. 

PMID- 24664111
TI  - Distinctive glial and neuronal interfacing on nanocrystalline diamond.
AB  - Direct electrode/neuron interfacing is a key challenge to achieve high resolution
      of neuronal stimulation required for visual prostheses. Neuronal interfacing on
      biomaterials commonly requires the presence of glial cells and/or protein
      coating. Nanocrystalline diamond is a highly mechanically stable biomaterial with
      a remarkably large potential window for the electrical stimulation of tissues.
      Using adult retinal cell cultures from rats, we found that glial cells and
      retinal neurons grew equally well on glass and nanocrystalline diamond. The use
      of a protein coating increased cell survival, particularly for glial cells.
      However, bipolar neurons appeared to grow even in direct contact with bare
      diamond. We investigated whether the presence of glial cells contributed to this
      direct neuron/diamond interface, by using purified adult retinal ganglion cells
      to seed diamond and glass surfaces with and without protein coatings.
      Surprisingly, these fully differentiated spiking neurons survived better on
      nanocrystalline diamond without any protein coating. This greater survival was
      indicated by larger cell numbers and the presence of longer neurites. When a
      protein pattern was drawn on diamond, neurons did not grow preferentially on the
      coated area, by contrast to their behavior on a patterned glass. This study
      highlights the interesting biocompatibility properties of nanocrystalline
      diamond, allowing direct neuronal interfacing, whereas a protein coating was
      required for glial cell growth. 

PMID- 24664112
TI  - Denitrifier community in the oxygen minimum zone of a subtropical deep reservoir.
AB  - Denitrification is an important pathway for nitrogen removal from aquatic systems
      and this could benefit water quality. However, little is known about the
      denitrifier community composition and key steps of denitrification in the
      freshwater environments, and whether different bacteria have a role in multiple
      processes of denitrification reduction. In this study, quantitative PCR,
      quantitative RT-PCR, clone library and 454 pyrosequencing were used together to
      investigate the bacterial and denitrifier community in a subtropical deep
      reservoir during the strongly stratified period. Our results indicated that the
      narG gene recorded the highest abundance among the denitrifying genes (2.76*109
      copies L-1 for DNA and 4.19*108 copies L-1 for RNA), and the lowest value was
      nosZ gene (7.56*105 copies L-1 for DNA and undetected for RNA). The RNA: DNA
      ratios indicated that narG gene was the most active denitrifying gene in the
      oxygen minimum zone of Dongzhen Reservoir. Further, alpha-, beta- and gamma-
      Proteobacteria were the overwhelmingly dominant classes of denitrifier
      communities. Each functional gene had its own dominant groups which were
      different at the genus level: the narG gene was dominated by Albidiferax, while
      nirS gene was dominated by Dechloromonas. The main OTU of nirK gene was
      Rhodopseudomonas palustris, but for norB and nosZ genes, they were Bacillus and
      Bradyrhizobium, respectively. These results contribute to the understanding of
      linkages between denitrifier community, function and how they work together to
      complete the denitrification process. Studies on denitrifier community and
      activity may be useful in managing stratified reservoirs for the ecosystem
      services and aiding in constructing nitrogen budgets. 

PMID- 24664113
TI  - Premarket approval supplement pathway: do we know what we are getting?

PMID- 24664115
TI  - Living on the edge: demography of the slender-billed gull in the Western
      Mediterranean.
AB  - Small and peripheral populations are typically vulnerable to local extinction
      processes but important for the metapopulation dynamics of species. The Slender
      billed gull (Chroicocephalus genei) is a long-lived species breeding in unstable
      ephemeral coastal habitats. Their Western Mediterranean populations are
      relatively small and represent the edge of their global geographical
      distribution. At a local scale, using long-term data (14 years) on annual
      breeding success and capture-resights of marked individuals, we estimated and
      compared the vital rates and evaluated the connectivity of two Spanish
      populations (Ebro Delta and Donana) varying in their local environmental
      conditions. At a metapopulation scale, we analyzed 22 years of data on breeding
      numbers to predict their future prospects by means of population demographic
      models. Local survival and breeding success of gulls from the Ebro Delta was
      lower than those from Donana, which is likely the result of higher permanent
      emigration and/or winter mortality in the former. Gulls from the Ebro Delta
      wintered mostly in Mediterranean areas whereas those from Donana did so in
      Atlantic coasts, where food availability is higher. Whereas adult local survival
      was constant, juvenile local survival showed temporal parallel variations between
      colonies, probably related to natal dispersal to other breeding colonies. Our
      results suggested that dispersal was higher at the Ebro Delta and gulls
      emigrating from their natal colonies settled preferentially in close patches. We
      found large fluctuations in breeding numbers among local populations probably
      related to the fact that the Slender-billed gull is a species adapted to unstable
      and unpredictable habitats with high abilities to disperse between suitable
      patches depending on environmental stochastic conditions during breeding. 

PMID- 24664116
TI  - Predicting phosphorescent lifetimes and zero-field splitting of organometallic
      complexes with time-dependent density functional theory including spin-orbit
      coupling.
AB  - The (photo)physical properties of organometallic complexes are crucially affected
      by relativistic effects. In a non- or scalar-relativistic picture, triplet states
      are threefold degenerate. Spin-orbit coupling lifts this degeneracy (zero-field
      splitting, ZFS) and enables phosphorescence from the three triplet-like states to
      the ground state. The fine structure and radiative lifetimes of phosphorescent
      organometallic complexes are important properties for designing efficient organic
      light-emitting diodes (OLEDs). Here we show that experimental ZFSs and
      phosphorescent lifetimes for a large variety of organometallic complexes are well
      reproduced by self-consistent spin-orbit coupling TDDFT (SOC-TDDFT) calculations
      with a continuum solvation model. By comparing with perturbative SOC-TDDFT and
      gas phase calculations, we find that both full spin-orbit and solvation effects
      are important for the predicted properties. SOC-TDDFT is thus shown to be a
      useful predictive tool for the rational design of phosphors in OLEDs and other
      optoelectronic devices. 

PMID- 24664114
TI  - Parallel workflow for high-throughput (>1,000 samples/day) quantitative analysis
      of human insulin-like growth factor 1 using mass spectrometric immunoassay.
AB  - Insulin-like growth factor 1 (IGF1) is an important biomarker for the management
      of growth hormone disorders. Recently there has been rising interest in deploying
      mass spectrometric (MS) methods of detection for measuring IGF1. However,
      widespread clinical adoption of any MS-based IGF1 assay will require increased
      throughput and speed to justify the costs of analyses, and robust industrial
      platforms that are reproducible across laboratories. Presented here is an MS
      based quantitative IGF1 assay with performance rating of >1,000 samples/day, and
      a capability of quantifying IGF1 point mutations and posttranslational
      modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA)
      benefited from a simplified sample preparation step, IGF1 immunocapture in a tip
      format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and
      Limit of Quantification of the resulting assay were 1.5 MUg/L and 5 MUg/L,
      respectively, with intra- and inter-assay precision CVs of less than 10%, and
      good linearity and recovery characteristics. The IGF1 MSIA was benchmarked
      against commercially available IGF1 ELISA via Bland-Altman method comparison
      test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in
      an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS
      instruments synced into one-hour phases of sample preparation, extraction and
      MSIA pipette tip elution, MS data collection, and data processing. Using this
      workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved
      in approximately 9 hours. This rate of assaying is a significant improvement over
      existing MS-based IGF1 assays, and is on par with that of the enzyme-based
      immunoassays. Furthermore, a mutation was detected in ~1% of the samples (SNP:
      rs17884626, creating an A->T substitution at position 67 of the IGF1),
      demonstrating the capability of IGF1 MSIA to detect point mutations and
      posttranslational modifications. 

PMID- 24664117
TI  - Identification and characterization of RING-finger ubiquitin ligase UBR7 in
      mammalian spermatozoa.
AB  - The ubiquitin-proteasome system (UPS) controls intracellular protein turnover in
      a substrate-specific manner via E3-type ubiquitin ligases. Mammalian
      fertilization and particularly sperm penetration through the oocyte vitelline
      coat, the zona pellucida (ZP), is regulated by UPS. We use an extrinsic substrate
      of the proteasome-dependent ubiquitin-fusion degradation pathway, the mutant
      ubiquitin UBB(+1), to provide evidence that an E3-type ligase activity exists in
      sperm-acrosomal fractions. Protein electrophoresis gels from such de novo
      ubiquitination experiments contained a unique protein band identified by tandem
      mass spectrometry as being similar to ubiquitin ligase UBR7 (alternative name:
      C14ORF130). Corresponding mRNA was amplified from boar testis and several
      variants of the UBR7 protein were detected in boar, mouse and human sperm
      extracts by Western blotting. Genomic analysis indicated a high degree of
      evolutionary conservation, remarkably constant purifying selection and conserved
      testis expression of the UBR7 gene. By immunofluorescence, UBR7 was localized to
      the spermatid acrosomal cap and sperm acrosome, in addition to hotspots of
      proteasomal activity in spermatids, such as the cytoplasmic lobe, caudal
      manchette, nucleus and centrosome. During fertilization, UBR7 remained with the
      ZP-bound acrosomal shroud following acrosomal exocytosis. Thus, UBR7 is present
      in the acrosomal cap of round spermatids and within the acrosomal matrix of
      mature boar spermatozoa. These data provide the first evidence of ubiquitin
      ligase activity in mammalian spermatozoa and indicate UBR7 involvement in
      spermiogenesis.

PMID- 24664118
TI  - Developmental changes in the protective effect of exogenous brain-derived
      neurotrophic factor and neurotrophin-3 against ototoxic drugs in cultured rat
      vestibular ganglion neurons.
AB  - We examine developmental changes in the responsiveness of rat vestibular ganglion
      neurons (VGNs) to two neurotrophic factors (NTFs), brain-derived neurotrophic
      factor (BDNF) and neurotrophin-3 (NT-3) and investigate the protective effects of
      these NTFs against ototoxic drugs during postnatal development in dissociated
      cultures. VGNs were obtained from rats on postnatal days (P) 1, 3, 7 and 14. BDNF
      facilitated neuronal survival as well as neurite sprouting of VGNs obtained from
      younger rats (P1 and P3), whereas these effects were not observed in older rats
      (P7 and P14). BDNF was also effective in facilitating neurite extension in VGNs
      at each of the postnatal ages. NT-3 also facilitated neuronal survival and
      neurite extension of VGNs from younger rats but these effects were significantly
      smaller than those of BDNF (p < 0.05). The protective effects of BDNF and NT-3
      against ototoxic drugs, gentamicin and cisplatin, were also age-dependent: they
      were effective for neuronal survival, neurite sprouting and neurite extension in
      VGNs from younger rats, whereas these effects tended to disappear in VGNs from
      older rats. Analysis of the changes in the expression of the receptors of NTFs
      revealed that expression of TrkB and TrkC proteins and their mRNA did not change
      during the developmental period, whereas expression of p75(NTR) protein was down
      regulated together with that of p75(NTR) mRNA during the developmental period.
      Developmental changes in the responsiveness to exogenous NTFs in VGNs, which is
      not caused by the changes of their receptors but probably caused by changes in
      the intracellular signaling pathways, should be taken into consideration in the
      prevention of neuronal degeneration caused by ototoxic drugs.

PMID- 24664119
TI  - Acidity in DMSO from the embedded cluster integral equation quantum solvation
      model.
AB  - The embedded cluster reference interaction site model (EC-RISM) is applied to the
      prediction of acidity constants of organic molecules in dimethyl sulfoxide (DMSO)
      solution. EC-RISM is based on a self-consistent treatment of the solute's
      electronic structure and the solvent's structure by coupling quantum-chemical
      calculations with three-dimensional (3D) RISM integral equation theory. We
      compare available DMSO force fields with reference calculations obtained using
      the polarizable continuum model (PCM). The results are evaluated statistically
      using two different approaches to eliminating the proton contribution: a linear
      regression model and an analysis of pK(a) shifts for compound pairs. Suitable
      levels of theory for the integral equation methodology are benchmarked. The
      results are further analyzed and illustrated by visualizing solvent site
      distribution functions and comparing them with an aqueous environment.

PMID- 24664120
TI  - Two new atom centered fragment descriptors and scoring function enhance
      classification of antibacterial activity.
AB  - Classification of pharmacologic activity of a chemical compound is an essential
      step in any drug discovery process. We develop two new atom-centered fragment
      descriptors (vertex indices)--one based solely on topological considerations
      without discriminating atom or bond types, and another based on topological and
      electronic features. We also assess their usefulness by devising a method to rank
      and classify molecules with regard to their antibacterial activity.
      Classification performances of our method are found to be superior compared to
      two previous studies on large heterogeneous data sets for hit finding and hit-to
      lead studies even though we use much fewer parameters. It is found that for hit
      finding studies topological features (simple graph) alone provide significant
      discriminating power, and for hit-to-lead process small but consistent
      improvement can be made by additionally including electronic features (colored
      graph). Our approach is simple, interpretable, and suitable for design of
      molecules as we do not use any physicochemical properties. The singular use of
      vertex index as descriptor, novel range based feature extraction, and rigorous
      statistical validation are the key elements of this study.

PMID- 24664121
TI  - On the regioselectivity of the mononuclear copper-catalyzed cycloaddition of
      azide and alkynes (CuAAC). A quantum chemical topological study.
AB  - New density functional theory (DFT) calculations show that the nature of the
      mechanism for the classical copper-catalyzed cycloaddition of azide to terminal
      alkynes--widely known as the CuAAC reaction--also depends on the ligands attached
      to Cu(I). Further, the topological evolution of the charge density, rho (r), the
      laplacian of rho (r), ?2rho(r), and its gradient field along the reaction
      coordinate shed light on the regioselectivity of the process. The performance of
      most suitable functionals for DFT calculations in this kind of system was tested.

PMID- 24664122
TI  - Tunable interactions between paramagnetic colloidal particles driven in a
      modulated ratchet potential.
AB  - We study experimentally and theoretically the interactions between paramagnetic
      particles dispersed in water and driven above the surface of a stripe patterned
      magnetic garnet film. An external rotating magnetic field modulates the stray
      field of the garnet film and generates a translating potential landscape which
      induces directed particle motion. By varying the ellipticity of the rotating
      field, we tune the inter-particle interactions from net repulsive to net
      attractive. For attractive interactions, we show that pairs of particles can
      approach each other and form stable doublets which afterwards travel along the
      modulated landscape at a constant mean speed. We measure the strength of the
      attractive force between the moving particles and propose an analytically
      tractable model that explains the observations and is in quantitative agreement
      with experiment. 

PMID- 24664123
TI  - Exploiting lanthanide luminescence in supramolecular assemblies.
AB  - Lanthanide ions, due to their unique photo-physical characteristics, have
      attracted considerable attention in recent years. Their long lifetimes, sharp,
      well-defined emission bands, and designable environmental sensitivity make them
      ideal for integration into switchable supramolecular assemblies where emission
      can report on local conformation and/or coupled energy levels (redox state). The
      immobilisation of lanthanide containing constructs on interfaces facilitates
      device integration, the fabrication of advanced sensory and molecular electronic
      platforms and presents a means by which conformational dynamics within molecular
      assemblies can be analysed. In this feature article we discuss the current and
      potential applications for lanthanide luminescence in supramolecular, switchable
      and surface bound architectures. 

PMID- 24664124
TI  - Visual ecology of flies with particular reference to colour vision and colour
      preferences.
AB  - The visual ecology of flies is outstanding among insects due to a combination of
      specific attributes. Flies' compound eyes possess an open rhabdom and thus
      separate rhabdomeres in each ommatidium assigned to two visual pathways. The
      highly sensitive, monovariant neural superposition system is based on the
      excitation of the peripheral rhabdomeres of the retinula cells R1-6 and controls
      optomotor reactions. The two forms of central rhabdomeres of R7/8 retinula cells
      in each ommatidium build up a system with four photoreceptors sensitive in
      different wavelength ranges and thought to account for colour vision. Evidence
      from wavelength discrimination tests suggests that all colour stimuli are
      assigned to one of just four colour categories, but cooperation of the two
      pathways is also evident. Flies use colour cues for various behavioural reactions
      such as flower visitation, proboscis extension, host finding, and egg deposition.
      Direct evidence for colour vision, the ability to discriminate colours according
      to spectral shape but independent of intensity, has been demonstrated for few fly
      species only. Indirect evidence for colour vision provided from
      electrophysiological recordings of the spectral sensitivity of photoreceptors and
      opsin genes indicates similar requisites in various flies; the flies' responses
      to coloured targets, however, are much more diverse. 

PMID- 24664126
TI  - Gendered Language in Interactive Discourse.
AB  - Over two studies, we examined the nature of gendered language in interactive
      discourse. In the first study, we analyzed gendered language from a chat corpus
      to see whether tokens of gendered language proposed in the gender-as-culture
      hypothesis (Maltz and Borker in Language and social identity. Cambridge
      University Press, Cambridge, pp 196-216, 1982) can be found in interactive
      language. Of the eight tokens examined only three were found to differ in the
      hypothesized direction, and these only in male-male dyads. In the second study,
      we trained a male and a female confederate to use either male or female gendered
      tokens found to be reliable in Study One in their chats with participants. Our
      design permits disentangling of effects due to knowledge of the gender of the
      interlocutors and use of specific language tokens. We find that use of language
      tokens by the confederate promoted use of the same token by their interlocutor,
      regardless of knowledge of the confederate's gender. Moreover use of tokens
      consistent or inconsistent with visible gender influenced how the interlocutor
      perceived the confederate. Taken together these data are inconsistent with either
      the notion that gendered language is context independent (as suggested in the
      gender-as-culture hypothesis) or the notion that gendered language only emerges
      when gender is made salient, as would, in these studies, occur in mixed-gendered
      groups. 

PMID- 24664125
TI  - MicroRNA-663 induction upon oxidative stress in cultured human fibroblasts
      depends on the chronological age of the donor.
AB  - MicroRNAs, regulators of messenger RNA translation, have been observed to
      influence many physiological processes, amongst them the process of aging. Higher
      levels of microRNA-663 (miR-663) have previously been observed in human dermal
      fibroblasts subject to both replicative and stress-induced senescence compared to
      early passage cells. Also, higher levels of miR-663 have been found in memory T
      cells and in human fibroblasts derived from older donors compared to younger
      donors. In previous studies we observed that dermal fibroblasts from donors of
      different chronological and biological age respond differentially to oxidative
      stress measured by markers of cellular senescence and apoptosis. In the present
      study we set out to study the association between miR-663 levels and
      chronological and biological age. Therefore we tested in a total of 92 human
      dermal fibroblast strains whether the levels of miR-663 in non-stressed and
      stressed conditions (fibroblasts were treated with 0.6 MUM rotenone in stressed
      conditions) were different in young, middle aged and old donors and whether they
      were different in middle aged donors dependent on their biological age, as
      indicated by the propensity for familial longevity. In non-stressed conditions
      the level of miR-663 did not differ between donors of different age categories
      and was not dependent on biological age. Levels of miR-663 did not differ
      dependent on biological age in stressed conditions either. However, for different
      age categories the level of miR-663 in stressed conditions did differ: the level
      of miR-663 was higher at higher age categories. Also, the ratio of miR-663
      induction upon stress was significantly higher in donors from older age
      categories. In conclusion, we present evidence for an association of miR-663 upon
      stress and chronological age. 

PMID- 24664127
TI  - Cost-effective and eco-friendly synthesis of novel and stable N-doped ZnO/g-C3N4
      core-shell nanoplates with excellent visible-light responsive photocatalysis.
AB  - N-doped ZnO/g-C3N4 hybrid core-shell nanoplates have been successfully prepared
      via a facile, cost-effective and eco-friendly ultrasonic dispersion method for
      the first time. HRTEM studies confirm the formation of the N-doped ZnO/g-C3N4
      hybrid core-shell nanoplates with an average diameter of 50 nm and the g-C3N4
      shell thickness can be tuned by varying the content of loaded g-C3N4. The direct
      contact of the N-doped ZnO surface and g-C3N4 shell without any adhesive
      interlayer introduced a new carbon energy level in the N-doped ZnO band gap and
      thereby effectively lowered the band gap energy. Consequently, the as-prepared
      hybrid core-shell nanoplates showed a greatly enhanced visible-light
      photocatalysis for the degradation of Rhodamine B compare to that of pure N-doped
      ZnO surface and g-C3N4. Based on the experimental results, a proposed mechanism
      for the N-doped ZnO/g-C3N4 photocatalyst was discussed. Interestingly, the hybrid
      core-shell nanoplates possess high photostability. The improved photocatalytic
      performance is due to a synergistic effect at the interface of the N-doped ZnO
      and g-C3N4 including large surface-exposure area, energy band structure and
      enhanced charge-separation properties. Significantly, the enhanced performance
      also demonstrates the importance of evaluating new core-shell composite
      photocatalysts with g-C3N4 as shell material. 

PMID- 24664128
TI  - Three-dimensional ultrasonography in the diagnosis of deep endometriosis.
AB  - STUDY QUESTION: In the use of 'tenderness-guided' transvaginal ultrasound, is the
      diagnostic accuracy of three-dimensional (3D) ultrasonography better than two
      dimensional (2D) ultrasonography in the identification of deep endometriosis?
      SUMMARY ANSWER: Three-dimensional ultrasonography has a significantly higher
      diagnostic accuracy in the diagnosis of posterior locations of deep endometriosis
      without intestinal involvement, such as the uterosacral ligaments, vaginal and
      rectovaginal endometriosis. WHAT IS KNOWN ALREADY: The only previous study of the
      diagnosis of posterior compartment endometriosis reported an poor sensitivity of
      3D ultrasonography for uterosacral and sigmoid colon involvement. STUDY DESIGN,
      SIZE, DURATION: This diagnostic test study included 202 patients scheduled for
      surgery because of clinical suspicion of deep pelvic endometriosis and was
      carried out between January 2009 and September 2012. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Modified transvaginal ultrasonography was performed on all of
      the women by a single examiner. Two locations of deep endometriosis were
      considered: intestinal involvement and other posterior lesions (including vaginal
      location, rectovaginal septum and uterosacral ligaments). Once the 2D
      ultrasonography had been performed, the 3D acquisition was performed and the
      obtained volume was stored. To avoid the risk of recall bias, the same operator
      evaluated the 3D volumes 6 months after the last examination using virtual
      navigation to provide a presumptive diagnosis of the presence and localization of
      deep endometriosis. In addition, to evaluate the reproducibility of 3D, two
      operators with different levels of expertise performed a retrospective review of
      3D volumes from a random sample of 35 patients, twice, 1 week apart to also
      assess intraobserver agreement. The diagnostic performance of both tests was
      expressed as area under the receiver-operating characteristics curve (AUC),
      sensitivity, specificity, positive and negative predictive values, positive (LR+)
      and negative (LR-) likelihood ratios, with their respective 95% confidence
      interval (CI). Reproducibility was evaluated using kappa statistics. MAIN RESULTS
      AND THE ROLE OF CHANCE: Surgery revealed deep endometriosis in 129 patients. The
      AUCs for endometriosis of intestinal location were similar for both ultrasound
      techniques. The AUCs for endometriosis of other posterior locations were
      significantly different (0.891, 95% CI 0.839-0.943 for 3D versus 0.789, 95% CI
      0.720-0.858 for 2D; P = 0.0193). For the intestinal involvement, the specificity,
      sensitivity, positive and negative predictive value, and LR+ and LR- were 93% (89
      95%), 95% (88-98%), 89% (83-92%), 97% (93-99%), 13, and 0.06, respectively, for
      2D ultrasound and 97% (93-99%), 91% (84-94%), 95% (88-98%), 95% (91-96%), 25, and
      0.09, respectively, for 3D ultrasound. For other posterior locations, the
      specificity, sensitivity, positive and negative predictive value, and LR+ and LR-
      were 88% (82-93%), 71% (64-77%), 83% (75-90%), 79% (74-83%), 6.10, 0.32,
      respectively, for 2D ultrasound and 94% (89-97%), 87% (81-91%), 92% (86-96%), 90%
      (85-93%), 14.0, 0.14, respectively, for 3D ultrasound. Intraobserver agreement
      was substantial for both examiners (kappa 0.8754, for operator A and 0.7087, for
      operator B, respectively). Interobserver agreement was also substantial.
      LIMITATIONS, REASONS FOR CAUTION: The disadvantages of 3D ultrasound to be
      considered are the necessity of newer ultrasonographic equipment and that fewer
      sonographers completely know the 3D technique. There are also some limitations
      within this study. First, an expert examiner performed the real-time ultrasound
      and 3D volume acquisitions. Second, the same operator also performed the 3D
      evaluations but at least 6 months after the last acquisition to avoid a possible
      recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The diagnostic performance
      obtained in the present study is superior to the accuracy reported in other
      studies of 3D ultrasonography, but not superior to all other published articles
      of 2D ultrasonography. The reported high diagnostic accuracy of 3D ultrasound
      could be widely generalizable because good reproducibility was demonstrated even
      with an operator with less expertise. STUDY FUNDING/COMPETING INTEREST(S): This
      study was supported in part by the Regione Autonoma della Sardegna (project code
      CPR-24750).

PMID- 24664129
TI  - Uterine peristalsis before embryo transfer affects the chance of clinical
      pregnancy in fresh and frozen-thawed embryo transfer cycles.
AB  - STUDY QUESTION: Does uterine peristalsis influence the chance of clinical
      pregnancy in an embryo transfer cycle? SUMMARY ANSWER: The uterine peristaltic
      wave frequency before embryo transfer is inversely related to the clinical
      pregnancy rates in fresh and frozen-thawed embryo transfer cycles. WHAT IS KNOWN
      ALREADY: Uterine peristalsis participates in regulating fluid migration after
      mock embryo transfer, but whether it could potentially influence pregnancy
      outcomes had remained unclear. STUDY DESIGN, SIZE, DURATION: This prospective
      cohort study included a total of 292 infertile women and was conducted between
      March 2013 and August 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients
      underwent fresh embryo transfer in a fresh stimulation cycle with a long down
      regulation protocol, a natural frozen-thawed embryo transfer cycle or an
      artificial frozen-thawed embryo transfer cycle. Uterine peristaltic activity was
      assessed before embryo transfer by transvaginal ultrasonography. MAIN RESULTS AND
      THE ROLE OF CHANCE: The uterine peristaltic wave frequencies of most patients
      were between 1.1 and 3.0 waves/min before embryo transfer (ET). The clinical
      pregnancy rate was the highest when <2.0 waves/min was observed and it decreased
      with an increasing wave frequency thereafter, with an especially dramatic
      decrease with >3.0 waves/min. Uterine peristaltic wave frequencies of the non
      pregnant patient group were higher than that of the clinically-pregnant patient
      group in all types of transfer, fresh embryo transfer, natural FET or artificial
      FET cycle. Binary logistic regression analysis demonstrated that the association
      between uterine peristaltic wave frequency before embryo transfer and clinical
      pregnancy was independently significant (odds ratio: 0.49; 95% confidence
      interval: 0.34-0.70, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Uterine
      peristalsis after embryo transfer was not observed in case any possible negative
      effect of the observation disturbed embryo implantation or caused psychological
      stress. Uterine peristalsis after embryo transfer may differ from that before
      embryo transfer. Another limitation of the present study was the lack of uterine
      peristaltic wave type analysis which is also an important parameter to assess
      uterine activity. WIDER IMPLICATIONS OF THE FINDINGS: Patients with uterine
      peristalsis of <3.0 waves/min before embryo transfer had a higher chance of
      pregnancy compared with those with higher frequencies. This could be a promising
      quantitative marker of uterine receptivity and pregnancy outcome in an embryo
      transfer cycle. The predictive validity of the cut-off value needs to be tested
      in further study. STUDY FUNDING/COMPETING INTEREST(S): The study is supported by
      Hunan Provincial Innovation Foundation for Postgraduates. The authors declare
      that they have no competing interests in this study.

PMID- 24664130
TI  - Preconception stress increases the risk of infertility: results from a couple
      based prospective cohort study--the LIFE study.
AB  - STUDY QUESTION: Are women's stress levels prospectively associated with fecundity
      and infertility? SUMMARY ANSWER: Higher levels of stress as measured by salivary
      alpha-amylase are associated with a longer time-to-pregnancy (TTP) and an
      increased risk of infertility. WHAT IS KNOWN ALREADY: Data suggest that stress
      and reproduction are interrelated; however, the directionality of that
      association is unclear. STUDY DESIGN, SIZE, DURATION: In 2005-2009, we enrolled
      501 couples in a prospective cohort study with preconception enrollment at two
      research sites (Michigan and Texas, USA). Couples were followed for up to 12
      months as they tried to conceive and through pregnancy if it occurred. A total of
      401 (80%) couples completed the study protocol and 373 (93%) had complete data
      available for this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Enrolled
      women collected saliva the morning following enrollment and then the morning
      following their first observed study menses for the measurement of cortisol and
      alpha-amylase, which are biomarkers of stress. TTP was measured in cycles.
      Covariate data were captured on both a baseline questionnaire and daily journals.
      MAIN RESULTS AND THE ROLE OF CHANCE: Among the 401 (80%) women who completed the
      protocol, 347 (87%) became pregnant and 54 (13%) did not. After adjustment for
      female age, race, income, and use of alcohol, caffeine and cigarettes while
      trying to conceive, women in the highest tertile of alpha-amylase exhibited a 29%
      reduction in fecundity (longer TTP) compared with women in the lowest tertile
      [fecundability odds ratios (FORs) = 0.71; 95% confidence interval (CI) = (0.51,
      1.00); P < 0.05]. This reduction in fecundity translated into a >2-fold increased
      risk of infertility among these women [relative risk (RR) = 2.07; 95% CI = (1.04,
      4.11)]. In contrast, we found no association between salivary cortisol and
      fecundability. LIMITATIONS, REASONS FOR CAUTION: Due to fiscal and logistical
      concerns, we were unable to collect repeated saliva samples and perceived stress
      questionnaire data throughout the duration of follow-up. Therefore, we were
      unable to examine whether stress levels increased as women continued to fail to
      get pregnant. Our ability to control for potential confounders using time-varying
      data from the daily journals, however, minimizes residual confounding. WIDER
      IMPLICATIONS OF THE FINDINGS: This is the first US study to demonstrate a
      prospective association between salivary stress biomarkers and TTP, and the first
      in the world to observe an association with infertility. STUDY FUNDING/COMPETING
      INTEREST(S): This study was supported by the Intramural Research Program of the
      Eunice Kennedy Shriver National Institute of Child Health and Human Development
      (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of
      interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 24664132
TI  - Animacy or case marker order?: priority information for online sentence
      comprehension in a head-final language.
AB  - It is well known that case marker information and animacy information are
      incrementally used to comprehend sentences in head-final languages. However, it
      is still unclear how these two kinds of information are processed when they are
      in competition in a sentence's surface expression. The current study used
      sentences conveying the potentiality of some event (henceforth, potential
      sentences) in the Japanese language with theoretically canonical word order
      (dative-nominative/animate-inanimate order) and with scrambled word order
      (nominative-dative/inanimate-animate order). In Japanese, nominative-first case
      order and animate-inanimate animacy order are preferred to their reversed
      patterns in simplex sentences. Hence, in these potential sentences, case
      information and animacy information are in competition. The experiment consisted
      of a self-paced reading task testing two conditions (that is, canonical and
      scrambled potential sentences). Forty-five native speakers of Japanese
      participated. In our results, the canonical potential sentences showed a
      scrambling cost at the second argument position (the nominative argument). This
      result indicates that the theoretically scrambled case marker order (nominative
      dative) is processed as a mentally canonical case marker order, suggesting that
      case information is used preferentially over animacy information when the two are
      in competition. The implications of our findings are discussed with regard to
      incremental simplex sentence comprehension models for head-final languages. 

PMID- 24664133
TI  - Inhibition of Enterovirus 71 replication by 7-hydroxyflavone and diisopropyl
      flavon7-yl Phosphate.
AB  - Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth
      disease, which has been continuously prevalent in Asia in recent years. In
      children, severe cases can lead to death, and no prophylactic or therapeutic
      measures against EV71 infection are available. The 3C proteases of EV71 play an
      important role in viral replication and are an ideal drug target. In previous
      work, we resolved the crystal structure for EV71 3Cpro. In this report, we took
      advantage of the automated docking program AutoDock 4.0 to simulate EV71 3Cpro
      ligand conformation. 7-hydroxyflavone (HF) and its phosphate ester(FIP) were
      predicted to bind with EV71 3Cpro.In an in vitro protease inhibition assay, FIP
      inhibited EV71 3Cpro protease activity. Both flavones were highly active against
      EV71, protecting cells from EV71 infection. Replication of viral RNA and
      formation of EV71 plaque were all strongly inhibited in cells. These results
      indicated that HF and FIP may serve as potential protective agents in the
      treatment of patients with chronic EV71 infection. 

PMID- 24664134
TI  - [Endoprosthetic treatment of osteoporosis-related coxarthrosis : aspects of safe
      patient treatment].
AB  - BACKGROUND: With increasing life expectancy the prevalence of osteoarthritis is
      also substantially rising. Patients aged between 65 and 75 years scheduled for
      total joint arthroplasty suffer from undetected osteoporosis in 20-25% of cases.
      OBJECTIVES: How to determine osteoporosis during preoperative workup? Which
      conclusions can be drawn for the operation treatment and the postoperative
      course? METHODS: The literature dealing with the prevalence of osteoporosis,
      perioperative complications of total hip arthroplasty, selected register
      informations, guidelines for diagnostics and treatment of osteoporosis and for
      the postoperative treatment are summarized and discussed. RESULTS: The fracture
      risk is determined according to the guidelines of the Dachverband Osteologie
      (DVO, Governing Body on Osteology). The implant and the anchorage are selected
      based on the risk of suffering from osteoporosis. An intraoperative fracture and
      early aseptic loosening are the main operative risk factors. For the
      postoperative course in addition to education about arthroplasty, adequate
      support for prevention of falls is mandatory. Continuous physiotherapy with
      muscular strengthening is advisable. The long-term medication should be checked
      for risks in the PRISCUS list of potentially inappropriate medication in the
      elderly and non-steroidal anti-inflammatory drugs (NSAIDs) should not be
      prescribed in patients with cardiac comorbidities. Patients with confirmed
      osteoporosis should be treated with antiresorptive agents.

PMID- 24664135
TI  - Biomechanical comparison of the interval throwing program and baseball pitching:
      upper extremity loads in training and rehabilitation.
AB  - BACKGROUND: The interval throwing progression has been part of baseball
      rehabilitation and conditioning for decades, yet little is known about the upper
      extremity loads an athlete is subjected to during this progression. HYPOTHESIS: A
      biomechanical comparison of fastball pitching, variable-effort pitching, and
      throwing various flat-ground distances will show significant torque differences
      in the throwing shoulder and elbow. STUDY DESIGN: Descriptive laboratory study.
      METHODS: Twenty-nine healthy college baseball pitchers were analyzed using a
      quantitative motion analysis system. The participants threw from flat ground at
      distances of 18, 27, 37, and 55 m, having been instructed to throw "hard, on a
      horizontal line." The participants then threw fastballs 18.4 m from a mound at 3
      different effort levels: 60%, 80%, and full effort. The kinetic values for
      humeral internal rotational torque (HIRT) and elbow valgus load (EVL) were
      extracted for each throw. Repeated-measures analyses of variance (ANOVAs) were
      used to compare all 7 throwing conditions within pitchers. The kinetic data were
      also compared against ball velocity to evaluate throwing efficiency. A separate
      analysis was conducted using a 3-level repeated-measures ANOVA with post hoc
      paired t tests comparing just the variable-effort throws from the mound. RESULTS:
      No statistically significant differences were found in either HIRT or EVL between
      any of the flat-ground distances and throwing from the mound (P > .05). Despite
      similar biomechanical loads compared with the mound, throwing from flat ground
      showed significantly decreased ball velocity (82% of maximum). Statistically
      significant differences were found in humeral internal rotational torque and
      elbow valgus load between fastball pitching off the mound at 60% and 100%, as
      these parameters increased with throwing effort (P < .05). At 60% perceived
      effort from the mound, pitchers generated forces of 76% and ball speeds
      approaching 84% of maximum. CONCLUSION: Partial-effort pitching demonstrates
      significantly lower loads on the shoulder and elbow. Flat-ground throwing at even
      the shortest distances had similar biomechanical loads compared with pitching
      from the mound, yet at significantly lower ball velocity. This illustrates the
      mechanical advantage and increased efficiency of throwing from a mound. No
      increase in shoulder or elbow loads was seen with increasing distances from flat
      ground, as pitchers began using a "crow hop" for the longer distances,
      facilitating the throw with their lower extremity. The mechanical advantage of
      throwing from a mound or using the crow hop is likely protective during
      rehabilitation and training throws. CLINICAL RELEVANCE: The findings of this
      study may be used to improve rehabilitation programs designed for baseball
      players returning from shoulder or elbow injury.

PMID- 24664136
TI  - The Effect of NSAID Prophylaxis and Operative Variables on Heterotopic
      Ossification After Hip Arthroscopy.
AB  - BACKGROUND: Heterotopic ossification (HO) is a known complication of hip
      arthroscopy. Little is known about the factors that lead to HO after hip
      arthroscopy. PURPOSE: The aim of this study was to evaluate the effect of
      nonsteroidal anti-inflammatory drugs (NSAIDs) and other operative variables on
      the development of HO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      A total of 357 consecutive cases of hip arthroscopy were retrospectively reviewed
      over a 3-year period. Routine NSAID prophylaxis was not performed for the first
      117 cases. Prophylaxis with naproxen for 3 weeks was then routinely prescribed
      for the remaining 240 cases. Complete follow-up was available for 288 of the
      original 357 cases. The presence of HO and its characteristics were recorded for
      each patient, along with baseline demographic and surgical variables. Odds ratios
      and logistic regression were used to identify causal factors for HO. RESULTS: The
      incidence of HO in cases in which the patient did not receive NSAID prophylaxis
      was 25.0% (23/92) versus 5.6% (11/196) of cases in which the patient received
      NSAIDs. Patients who received no NSAID prophylaxis were 13.6 times more likely to
      develop HO postoperatively (95% confidence interval, 2.44-75.5; P = .003).
      Comparing just mixed-type femoroacetabular impingement resections, patients who
      received no NSAID prophylaxis were 16.6 times more likely to develop HO
      postoperatively (95% confidence interval, 2.2-126.0; P = .006). Multivariate
      logistic regression identified the performance of a mixed-type femoroacetabular
      impingement resection (P = .011) and the absence of NSAID prophylaxis (P = .003)
      as predictors of HO development. The majority of HO cases (29/34) occurred in
      patients with mixed-type femoroacetabular impingement who had both
      osteochondroplasty and acetabuloplasty. Complications of NSAID therapy in this
      study population included acute renal failure, hematochezia from acute colitis,
      and gastritis. CONCLUSION: Routine NSAID prophylaxis reduces but does not
      eliminate the incidence of HO in patients undergoing hip arthroscopy. Heterotopic
      ossification was more likely to develop in patients undergoing acetabuloplasty
      along with osteochondroplasty and in those who did not receive prophylactic
      postoperative NSAIDs. Side effects from the investigated NSAID regimen can be
      serious and should be weighed against the potential benefits in preventing the
      formation of HO.

PMID- 24664137
TI  - Soft tissue knee injury with concomitant osteochondral fracture is associated
      with higher degree of acute joint inflammation.
AB  - BACKGROUND: Osteochondral fractures are often seen on magnetic resonance imaging
      (MRI) of acutely injured knees, but their existence has gained little interest
      because of a lack of knowledge of their relation to treatment options and
      outcome. It is not clear whether acute phase synovial fluid (SF) concentrations
      of cartilage and bone markers and proinflammatory cytokines are different between
      traumatically injured knees with or without osteochondral fracture. HYPOTHESIS:
      Acutely injured knees with an osteochondral fracture, particularly fractures with
      disrupted cortical bone, have higher concentrations of bone markers and cytokines
      than do knees without an osteochondral fracture. STUDY DESIGN: Cross-sectional
      study; Level of evidence, 3. METHODS: Synovial fluid (hemarthrosis) was aspirated
      (median 1 day after injury) and 1.5-T MRI was performed (median 8 days after
      injury) in the acutely injured knee of 98 individuals (26% women; mean age, 23
      years). As visualized on MRI, 39% knees had an osteochondral fracture with
      disrupted cortical bone, 30% had an osteochondral fracture with intact cortical
      bone, and 32% did not have an osteochondral fracture. Concentrations of sulfated
      glycosaminoglycan, ARGS aggrecan, cartilage oligomeric matrix protein,
      osteocalcin, secreted protein acidic and rich in cysteine (SPARC), osteopontin
      and proinflammatory cytokines (interleukin [IL]-1beta, IL-6, IL-8, and tumor
      necrosis factor [TNF]-alpha) were analyzed. RESULTS: After adjusting for days
      between injury and SF aspiration, age at injury, and sex, knees with any
      osteochondral fracture (with or without disrupted cortical bone) had
      significantly higher SF concentrations of TNF-alpha (median [interquartile range
      (IQR)] = 9 [7-12] pg/mL vs. 7 [5-14] pg/mL; P = .013), whereas knees with an
      osteochondral fracture with disrupted cortical bone had significantly higher SF
      concentrations (medians [IQRs]) of SPARC (492 [328-754] ng/mL vs. 407 [140-685]
      ng/mL; P = .030), IL-8 (278 [148-628] pg/mL vs. 138 [67-413] pg/mL; P = .028),
      and TNF-alpha (11 [7-15] pg/mL vs. 7 [5-14] pg/mL; P = .004) compared with knees
      without an osteochondral fracture. CONCLUSION: In acutely injured knees with
      hemarthrosis, a concomitant osteochondral fracture with disrupted cortical bone
      is associated with a higher degree of joint inflammation.

PMID- 24664138
TI  - Treatment of Full-Thickness Chondral Defects With Hyalograft C in the Knee: Long
      term Results.
AB  - BACKGROUND: Matrix-associated autologous chondrocyte transplantation (MACT) has
      become an established articular cartilage repair technique. It provides good
      short-term and midterm results; however, long-term results are lacking. PURPOSE:
      To prospectively assess the clinical outcome after MACT in the knee to report
      long-term results. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Fifty-three subjects (females/males, 22/31; mean age, 32 +/- 12 years) were
      treated between 2000 and 2006 with a hyaluronan-based MACT product and were
      followed prospectively. The mean body mass index (BMI) was 24.5 +/- 3.8 kg/m(2)
      and the mean defect size was 4.4 +/- 1.9 cm(2). Fifty patients had single defects
      and 3 had multiple defects (41 medial femoral condyle, 6 lateral femoral condyle,
      2 patella, 1 tibia). Two patients had 2 defects (medial femoral condyle
      [MFC]/lateral femoral condyle and tibial/MFC), and in 1 case, multiple defects on
      the MFC were treated. The patients were stratified into 23 "simple," 22
      "complex," and 8 "salvage" cases. Instability or malalignment was treated before
      or at the time of graft implantation. For 6 patients with small defects (<2
      cm(2)), microfracturing was used as first-line treatment before MACT. Clinical
      assessment was performed once a year with the subjective and objective
      International Knee Documentation Committee (IKDC) scores, Lysholm score, and a
      modified Cincinnati Knee Rating System. RESULTS: The mean follow-up time was 9.07
      +/- 2.9 years (range, 5-12 years). Treatment failure occurred in 12 of 53 cases
      (22.6%) an average of 2.99 +/- 1.40 years after surgery. There was 1 failure
      (4.3%) among the simple cases, 4 failures (18.2%) in complex cases, and 7
      failures (87.5%) in salvage cases. Statistically significant increases were
      observed in all scores at all time points compared with presurgery levels (P <
      .05). The subjective IKDC score improved from median 40.4 preoperatively to 74.7
      at 10-year follow-up (n = 13 patients; P < .05). CONCLUSION: MACT is an excellent
      surgical therapy for full-thickness cartilage defects of the knee, with good long
      term results for simple defects. However, it should not be used in salvage cases.

PMID- 24664139
TI  - Scapulothoracic bursitis and snapping scapula syndrome: a critical review of
      current evidence.
AB  - BACKGROUND: Symptomatic scapulothoracic disorders, such as painful scapular
      crepitus and/or bursitis, are uncommon; however, they can produce significant
      pain and disability in many patients. PURPOSE: To review the current knowledge
      pertaining to snapping scapula syndrome and to identify areas of further research
      that may be helpful to improve clinical outcomes and patient satisfaction. STUDY
      DESIGN: Systematic review. METHODS: We performed a preliminary search of the
      PubMed and Embase databases using the search terms "snapping scapula,"
      "scapulothoracic bursitis," "partial scapulectomy," and "superomedial angle
      resection" in September 2013. All nonreview articles related to the topic of
      snapping scapula syndrome were included. RESULTS: The search identified a total
      of 167 unique articles, 81 of which were relevant to the topic of snapping
      scapula syndrome. There were 36 case series of fewer than 10 patients, 16
      technique papers, 11 imaging studies, 9 anatomic studies, and 9 level IV outcomes
      studies. The level of evidence obtained from this literature search was
      inadequate to perform a formal systematic review or meta-analysis. Therefore, a
      critical review of current evidence is presented. CONCLUSION: Snapping scapula
      syndrome, a likely underdiagnosed condition, can produce significant shoulder
      dysfunction in many patients. Because the precise origin is typically unknown,
      specific treatments that are effective for some patients may not be effective for
      others. Nevertheless, bursectomy with or without partial scapulectomy is
      currently the most effective primary method of treatment in patients who fail
      nonoperative therapy. However, many patients experience continued shoulder
      disability even after surgical intervention. Future studies should focus on
      identifying the modifiable factors associated with poor outcomes after operative
      and nonoperative management for snapping scapula syndrome in an effort to improve
      clinical outcomes and patient satisfaction.

PMID- 24664140
TI  - Targeting mitochondria for neuroprotection in Parkinson disease.

PMID- 24664141
TI  - Direct visualization of CHIP-mediated degradation of alpha-synuclein in vivo:
      implications for PD therapeutics.
AB  - Parkinson's disease is a neurodegenerative disorder characterized by Lewy bodies,
      a pathological hallmark comprised mostly of aggregated alpha synuclein.
      Accumulating evidence demonstrates the association of smaller oligomeric
      aggregates to disease etiology and many therapeutic approaches are aimed at
      inhibiting and reducing the aggregation process. Molecular chaperones and co
      chaperones play a key role in protein homeostasis and have potential as
      therapeutics to inhibit alpha synuclein associated toxicity. Here we use a gene
      therapy approach to evaluate the applicability of the Hsp70 co-chaperone CHIP (C
      terminal Hsp70 interacting protein) as a therapeutic candidate and examine its
      direct effect on alpha synuclein aggregates in vivo. Utilizing a novel viral
      vector mediated rat model to directly detect alpha synuclein aggregates, we show
      that CHIP can mediate the degradation of alpha synuclein aggregates in vivo.
      However, our studies also reveal that CHIP may potentially degrade tyrosine
      hydroxylase which would compromise the applicability of CHIP as a therapeutic
      approach for Parkinson's disease. 

PMID- 24664142
TI  - Differential susceptibility of two field aedes aegypti populations to a low
      infectious dose of dengue virus.
AB  - BACKGROUND: The infectious dose required to infect mosquito vectors when they
      take a blood meal from a viremic person is a critical parameter underlying the
      probability of dengue virus (DENV) transmission. Because experimental vector
      competence studies typically examine the proportion of mosquitoes that become
      infected at intermediate or high DENV infectious doses in the blood meal, the
      minimum blood meal titer required to infect mosquitoes is poorly documented.
      Understanding the factors influencing the lower infectiousness threshold is
      epidemiologically significant because it determines the transmission potential of
      humans with a low DENV viremia, possibly including inapparent infections, and
      during the onset and resolution of the viremic period of acutely infected
      individuals. METHODOLOGY/PRINCIPAL FINDINGS: We compared the susceptibility of
      two field-derived Aedes aegypti populations from Kamphaeng Phet, Thailand when
      they were orally exposed to low titers of six DENV-2 isolates derived from the
      serum of naturally infected humans living in the same region. The infectious
      dose, time-point post-blood feeding, viral isolate and mosquito population, were
      significant predictors of the proportion of mosquitoes that became infected.
      Importantly, the dose-response profile differed significantly between the two Ae.
      aegypti populations. Although both mosquito populations had a similar 50% oral
      infectious dose (OID50), the slope of the dose-response was shallower in one
      population, resulting in a markedly higher susceptibility at low blood meal
      titers. CONCLUSIONS/SIGNIFICANCE: Our results indicate that mosquitoes in nature
      vary in their infectious dose-response to DENV. Thus, different mosquito
      populations have a differential ability to acquire DENV infection at low viremia
      levels. Future studies on human-to-mosquito DENV transmission should not be
      limited to OID50 values, but rather they should be expanded to account for the
      shape of the dose-response profile across a range of virus titers.

PMID- 24664143
TI  - Optical spectrum, perceived color, refractive index, and non-adiabatic dynamics
      of the photochromic diarylethene CMTE.
AB  - Photochromism allows for reversible light-induced conversion of a molecular
      species into a different form with significantly altered optical properties. One
      promising compound that excels with high fatigue resistance and shows its
      photochromic functionality both in solution and in molecular solid films is the
      diarylethene derivative CMTE. Here we present a comprehensive study of its
      photophysical properties with density-functional theory based methods and
      benchmark the results against higher-level quantum-chemical approaches and
      experiments. In addition to static properties such as optical absorption,
      perceived color, and refractive index, we also investigate reaction dynamics
      based on non-adiabatic ab initio molecular dynamics. This gives detailed insight
      into the molecules' ultrafast reaction dynamics and enables us to extract
      reaction time scales and quantum yields for the observed electrocyclic reaction
      following photoexcitation. 

PMID- 24664144
TI  - Therapeutic non-toxic doses of TNF induce significant regression in TNFR2-p75
      knockdown Lewis lung carcinoma tumor implants.
AB  - Tumor necrosis factor-alpha (TNF) binds to two receptors: TNFR1/p55-cytotoxic and
      TNFR2/p75-pro-survival. We have shown that tumor growth in p75 knockout (KO) mice
      was decreased more than 2-fold in Lewis lung carcinoma (LLCs). We hypothesized
      that selective blocking of TNFR2/p75 LLCs may sensitize them to TNF-induced
      apoptosis and affect the tumor growth. We implanted intact and p75 knockdown (KD)
      LLCs (>90%, using shRNA) into wild type (WT) mice flanks. On day 8 post
      inoculation, recombinant murine (rm) TNF-alpha (12.5 ng/gr of body weight) or
      saline was injected twice daily for 6 days. Tumor volumes (tV) were measured
      daily and tumor weights (tW) on day 15, when study was terminated due to large
      tumors in LLC+TNF group. Tubular bones, spleens and peripheral blood (PB) were
      examined to determine possible TNF toxicity. There was no significant difference
      in tV or tW between LLC minus (-) TNF and p75KD/LLC-TNF tumors. Compared to 3
      control groups, p75KD/LLC+TNF showed >2-5-fold decreases in tV (p<0.001) and tW
      (p<0.0001). There was no difference in tV or tW end of study vs. before
      injections in p75KD/LLC+TNF group. In 3 other groups tV and tW were increased 2.7
      4.5-fold (p<0.01, p<0.0002 and p<0.0001). Pathological examination revealed that
      1/3 of p75KD/LLC+rmTNF tumors were 100% necrotic, the remaining revealed 40-60%
      necrosis. No toxicity was detected in bone marrow, spleen and peripheral blood.
      We concluded that blocking TNFR2/p75 in LLCs combined with intra-tumoral rmTNF
      injections inhibit LLC tumor growth. This could represent a novel and effective
      therapy against lung neoplasms and a new paradigm in cancer therapeutics. 

PMID- 24664146
TI  - A gold-catalysed imine-propargylamine cascade sequence: synthesis of 3
      substituted-2,5-dimethylpyrazines and the reaction mechanism.
AB  - The gold-catalysed coupling reaction between propargylamine-derived imines and
      propargylamine exclusively afforded pyrazines. Besides, in order to understand
      the mechanism of this sequence, deuterium labeling and computational studies have
      been performed. 

PMID- 24664145
TI  - Clinical diagnosis, treatment, and ALDH7A1 mutations in pyridoxine-dependent
      epilepsy in three Chinese infants.
AB  - Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder that
      causes seizures in neonates and infants. Mutations of the ALDH7A1 gene are now
      recognized as the molecular basis PDE and help to define this disease. Three
      Chinese children with PDE were clinically analyzed, followed by treatment and
      examination of the ALDH7A1 mutations. The seizures of the 3 patients were all
      resistant to multiple anticonvulsants (2 to 7 types). For case 1, onset of
      seizures was at the age of 2 months. His seizures were well controlled by
      intravenous pyridoxine for several days at the age of 3 months 20 days and
      recurred at intervals of 13, 14 and 38 days after pyridoxine withdrawn for 3
      times. At the age of 7 months, symptoms of PDE appeared and uninterrupted oral
      pyridoxine started. For case 2, her seizures occurred at 8 days after birth.
      After administration of multiple antiepileptic drugs observed ineffective, high
      dose pyridoxine continuous therapy was taken at the age of 10 months and the
      significant treatment effect induced a diagnostic PDE. Seizure onset in case 3
      was at the first day of birth. He experienced inadvertently pyridoxine therapy
      several times (first time at 2 days after birth) and achieved good therapeutic
      effect, which was confirmed by physicians until 4 months 10 days. The treatment
      process in our 3 patients suggested that pyridoxine should be early and
      purposefully used in patients with early onset seizures. ALDH7A1 gene mutation
      analysis revealed compound heterozygous mutations in each case: heterozygous
      c.410G>A (p.G137E) and IVS11+1G>A in case 1, heterozygous c.952G>C (p.A318P) and
      heterozygous c.965C>T (p.A322V) in case 2, and heterozygous c.902A>T (p.N301I)
      and IVS11+1G>A in case 3. Only p.N301I was reported previously, all other
      mutations were novel. This is the first time to report cases of Chinese patients
      diagnosed with PDE by molecular genetic analysis. 

PMID- 24664147
TI  - Spanking and children's externalizing behavior across the first decade of life:
      evidence for transactional processes.
AB  - Despite a growing literature associating physical discipline with later child
      aggression, spanking remains a typical experience for American children. The
      directionality of the associations between aggression and spanking and their
      continuity over time has received less attention. This study examined the
      transactional associations between spanking and externalizing behavior across the
      first decade of life, examining not only how spanking relates to externalizing
      behavior leading up to the important transition to adolescence, but whether
      higher levels of externalizing lead to more spanking over time as well. We use
      data from the Fragile families and child well-being (FFCW) study to examine
      maternal spanking and children's behavior at ages 1, 3, 5, and 9 (N = 1,874; 48%
      girls). The FFCW is a longitudinal birth cohort study of children born between
      1998 and 2000 in 20 medium to large US cities. A little over a quarter of this
      sample was spanked at age 1, and about half at age 3, 5, and 9. Estimates from a
      cross-lagged path model provided evidence of developmental continuity in both
      spanking and externalizing behavior, but results also highlighted important
      reciprocal processes taking hold early, with spanking influencing later
      externalizing behavior, which, in turn, predicted subsequent spanking. These
      bidirectional effects held across race/ethnicity and child's gender. The findings
      highlight the lasting effects of early spanking, both in influencing early
      child's behavior, and in affecting subsequent child's externalizing and parental
      spanking in a reciprocal manner. These amplifying transactional processes
      underscore the importance of early intervention before patterns may cascade
      across domains in the transition to adolescence.

PMID- 24664149
TI  - LCST transition of PNIPAM-b-PVCL in water: cooperative aggregation of two
      distinct thermally responsive segments.
AB  - The self-aggregation behavior of poly(N-isopropylacrylamide)-b-poly(N
      vinylcaprolactam) (PNIPAM-b-PVCL) during the thermal-induced phase transition in
      water was explored by a combination of calorimetric, turbidity, dynamic light
      scattering (DLS) and FTIR measurements. Only one transition can be observed via
      all detecting methods, revealing the cooperative aggregation of the two distinct
      temperature-sensitive segments. What is more, the combination of strong
      hydrophobic interactions among the entire polymer chains and hydrogen bonds of
      C=O...H-N within PNIPAM segments results in the sharp variations at the LCST and
      gradual variations above the LCST during the phase transition of PNIPAM-b-PVCL
      aqueous solution upon heating. Additional analysis by perturbation correlation
      moving window (PCMW) and two-dimensional correlation spectroscopy (2Dcos)
      indicates that the hydrophobic C-H groups have an earlier response than the
      relatively hydrophilic C=O groups during the LCST transition.

PMID- 24664152
TI  - Only a very bold man would attempt to define death.

PMID- 24664151
TI  - International guideline development for the determination of death.
AB  - INTRODUCTION AND METHODS: This report summarizes the results of the first phase
      in the development of international guidelines for death determination, focusing
      on the biology of death and the dying process, developed by an invitational forum
      of international content experts and representatives of a number of professional
      societies. RESULTS AND CONCLUSIONS: Precise terminology was developed in order to
      improve clarity in death discussion and debate. Critical events in the
      physiological sequences leading to cessation of neurological and/or circulatory
      function were constructed. It was agreed that death determination is primarily
      clinical and recommendations for preconditions, confounding factors, minimum
      clinical standards and additional testing were made. A single operational
      definition of human death was developed: 'the permanent loss of capacity for
      consciousness and all brainstem functions, as a consequence of permanent
      cessation of circulation or catastrophic brain injury'. In order to complete the
      project, in the next phase, a broader group of international stakeholders will
      develop clinical practice guidelines, based on comprehensive reviews and grading
      of the existing evidence.

PMID- 24664153
TI  - Assessment of agreement and trending between haemodynamic monitors is still
      challenging.

PMID- 24664154
TI  - Blood glucose level and outcome after cardiac arrest: insights from a large
      registry in the hypothermia era.
AB  - INTRODUCTION: The influence of blood glucose (BG) level during the post
      resuscitation period after out-of-hospital cardiac arrest (OHCA) is still
      debated. To evaluate the relationship between blood glucose level and outcome, we
      included the median glycemia and its maximal amplitude over the first 48 h
      following ICU admission in an analysis of outcome predictors. METHODS: We
      conducted a database study in a cardiac arrest center in Paris, France. Between
      2006 and 2010, we included 381 patients who were all resuscitated from an OHCA. A
      moderate glycemic control was applied in all patients. The median glycemia and
      the largest change over the first 48 h were included in a multivariate analysis
      that was performed to determine parameters associated with a favorable outcome.
      RESULTS: Of the 381 patients, 136 (36 %) had a favorable outcome (CPC 1-2).
      Median BG level was 7.6 mmol/L (6.3-9.8) in patients with a favorable outcome
      compared to 9.0 mmol/L (IQR 7.1-10.6) for patients with an unfavorable outcome (p
      < 0.01). Median BG level variation was 7.1 (4.2-11) and 9.6 (5.9-13.6) mmol/L in
      patients with and without a favorable outcome, respectively (p < 0.01). In
      multivariate analysis, an increased median BG level over the first 48 h was found
      to be an independent predictor of poor issue [OR = 0.43; 95 % CI (0.24-0.78), p =
      0.006]. Finally a progressive increase in median BG level was associated with a
      progressive increase in the proportion of patients with a poor outcome.
      CONCLUSION: We observed a relationship between high blood glucose level and
      outcome after cardiac arrest. These results suggest the need to test a strategy
      combining both control of glycemia and minimization of glycemic variations for
      its ability to improve post-resuscitation care.

PMID- 24664156
TI  - Endometrial thickness and pregnancy rates after IVF: a systematic review and meta
      analysis.
AB  - BACKGROUND: Thin endometrium on ultrasound in the course of ovarian
      hyperstimulation has been thought to be associated with poor success rates after
      IVF, even in the absence of prior intrauterine surgery or infection. To assess
      the clinical significance of endometrial thickness (EMT) for IVF outcome, we
      performed a systematic review and meta-analysis. METHODS: The electronic
      databases Pubmed, Cochrane and Embase were searched up to October 2013 for
      articles that studied the association between EMT and IVF outcome. The articles
      had to be written in the English or Dutch language. Studies were included if two
      by-two tables for EMT and pregnancy rates could be constructed. Study quality was
      scored using the Strengthening the Reporting of Observational Studies in
      Epidemiology (STROBE) checklist. Summary receiver operating characteristic (sROC)
      curves were estimated to assess the accuracy of EMT in the prediction of
      pregnancy. In addition, odds ratios (ORs) with 95% confidence intervals (CIs)
      were calculated using a Mantel-Haenszel random effect model expressing the
      association between EMT and pregnancy chances. Meta-regression was performed to
      determine if female age and number of oocytes at retrieval interacted in the
      estimated effect of EMT on IVF outcome. RESULTS: A total of 1170 studies was
      retrieved by the search. The overall quality of the 22 studies included in the
      review and meta-analysis was moderate. The estimated sROC curve indicated a
      virtually absent discriminatory capacity of EMT in the prediction of pregnancy. A
      thin endometrium (<= 7 mm) was observed in only 2.4% of the reported cases
      (260/10 724). In these cases a trend towards lower ongoing pregnancy and live
      birth rates for women with EMT <= 7 mm was observed [OR 0.38 (95% CI 0.09-1.5)].
      The probability of clinical pregnancy for an EMT <= 7 mm was significantly lower
      compared with cases with EMT > 7 mm [23.3% versus 48.1%, OR 0.42 (95% CI 0.27
      0.67)]. Positive and negative predictive values for the outcome of clinical
      pregnancy 77 and 48%, respectively. The relationship between the number of
      oocytes and female age on the one hand and pregnancy on the other hand was very
      weak making correction for these variables unfeasible. CONCLUSIONS: Current data
      indicate that EMT has a limited capacity to identify women who have a low chance
      to conceive after IVF. The frequently reported cut-off of 7 mm is related to a
      lower chance of pregnancy, but occurs infrequently. The use of EMT as a tool to
      decide on cycle cancellation, freezing of all embryos or refraining from further
      IVF treatment seems not to be justified based on the current meta-analysis.
      Further research is needed to investigate the real independent significance of
      EMT in IVF.

PMID- 24664157
TI  - Annealing-free and strongly adhesive silver nanowire networks with long-term
      reliability by introduction of a nonconductive and biocompatible polymer binder.
AB  - As a promising candidate to replace the brittle and expensive transparent indium
      tin oxide (ITO) conductor, the use of silver nanowire (AgNW) networks still
      involves issues such as high-temperature post-treatments and poor substrate
      adhesion for industrial application. Here a room-temperature soldering and one
      step solution method is developed to achieve high-performance Ag nanowire
      transparent conductive films (TCFs). A nonconductive binder is prepared from
      poly(dopamine) and alginic acid which contains abundant catechol and carboxylic
      acid functional groups. The drying of the binder on the Ag nanowire percolation
      networks induces tighter contact among the nanowires and strong adhesion to the
      substrate, simultaneously enhancing the electrical and mechanical properties
      without a high-temperature annealing process. As a result, a highly conductive
      and bendable AgNW film is demonstrated on a low-cost polyethylene glycol
      terephthalate (PET) substrate, showing an 89% optical transmittance at lambda =
      550 nm and a sheet resistance of 16.3 Ohm sq(-1). Its optical and electrical
      performances are superior to those obtained from the reported indium tin oxide
      (ITO) films. Moreover, the AgNW film exhibits strong adhesion to the substrate,
      maintaining its conductivity after 100 tape tests, and it still resists the tape
      test even after exposure to solvent for several hours. Most importantly, the film
      shows good reliability during long-term 85  degrees C/85% RH (relative humidity)
      aging, which has been rarely investigated although it is a critical requirement
      for industrial application. The advanced and wide-ranging features of the
      prepared AgNW film greatly contribute to its use as a transparent electrode in
      multifunctional flexible electronic devices. 

PMID- 24664158
TI  - Surgical treatment of spontaneous posterior interosseous nerve palsy with
      hourglass-like constriction.

PMID- 24664159
TI  - Radiographic evaluation of a novel horizontal dorsal intercarpal capsulodesis as
      a treatment of pre-arthritic scapholunate dissociation: a cadaver study.
AB  - Dorsal capsulodesis is an important part of the treatment of pre-arthritic
      scapholunate instability. We designed an experimental study using 14 fresh-frozen
      cadaver wrists to demonstrate the efficacy of a new horizontal dorsal intercarpal
      capsulodesis. We sectioned the scapholunate ligament to create a scapholunate
      dislocation. Several radiographic views, static and 'in stress', were recorded
      and we statistically compared the scapholunate interval before and after the
      section of the scapholunate ligament, and after the creation of the capsulodesis.
      The results showed a significant decrease of the scapholunate interval after the
      creation of the capsulodesis, especially in neutral and maximal ulnar deviation
      of the wrist. They also proved that our cadaveric model is reliable. This study
      demonstrated that this novel capsulodesis reduces the scapholunate interval in a
      cadaveric model. 

PMID- 24664160
TI  - Dynamism in Dupuytren's contractures.
AB  - Dynamism of Dupuytren's contractures may occur if a contracture crosses over both
      the metacarpophalangeal (MCPJ) and proximal interphalangeal (PIPJ) joints of one
      finger. In this situation the extension deficit at one joint can be influenced by
      the position of the other. This may affect clinical measurements and introduce
      errors and bias into research using angular deformity as an endpoint. This study
      reports the dynamism encountered when measuring passive joint extension deficits
      in pre-operative contractures. Eighty-five digits with a contracture affecting
      the PIPJ or MCPJ and PIPJ on 72 hands from 70 patients were studied. Seventy-six
      digits showed dynamism at either the MCPJ or PIPJ (89%). Seventy-four showed
      dynamism at the PIPJ (87%). The mean dynamism observed was 6 degrees  at the MCPJ
      and 14 degrees  at the PIPJ. Previous Dupuytren's surgery to the finger did not
      influence the amount of dynamism seen. Dynamism is common and may be a source of
      error or bias in trials of Dupuytren's disease treatment.

PMID- 24664161
TI  - Free myocutaneous flap transfer to treat congenital Volkmann's contracture of the
      forearm.
AB  - The purpose of this study is to report our experience with free functional muscle
      transfer procedures for the late sequelae of the rare condition of congenital
      Volkmann's ischaemic contracture of the forearm. Four children, with an average
      age of 9.5 years (range 1.5-17), were treated and were followed for a mean of 6
      years (range 1-14). Two patients had dorsal forearm contractures, and two had
      both flexor and extensor forearm contractures. We carried out free functional
      muscle transfers to replace the flexor or extensor muscles. The functional result
      was assessed according to the classification system of Hovius and Ultee. All
      patients had wrist contractures and skeletal involvement with limb length
      discrepancy that influenced the outcome. All five transferred muscles survived
      and improved the function of the hand in three of the four patients. LEVEL OF
      EVIDENCE 4. 

PMID- 24664162
TI  - Volar perforators of common digital arteries: an anatomical study.
AB  - The palmar triangle is an area vascularized by perforator arteries arising from
      the common digital palmar arteries. The aim of this article was to perform an
      anatomical study of common digital palmar arteries perforators. Twelve injected
      specimens were included in this study. The purpose was to quantify the number of
      perforator arteries of each common digital palmar arteries in the 2nd, 3rd, and
      4th intermetacarpal space, measure distances between them, between the distal
      perforator and corresponding commissure, and the distance between the proximal
      perforator and the superficial palmar arch. Four to eight perforators were
      arising from common digital palmar arteries of the 2nd, 3rd, and 4th
      intermetacarpal space. The average distance between perforator arteries was 6.5
      mm, between superficial palmar arch and proximal perforator artery - 8.2 mm,
      between the distal perforator artery and corresponding commissure - 6.3 mm. 

PMID- 24664163
TI  - Hyaluronic acid scaffold for skin defects in congenital syndactyly release
      surgery: a novel technique based on the regenerative model.
AB  - Syndactyly release may require skin grafting to fill the skin defects, which
      might lead to complications or poor cosmetic outcomes. A simple graftless
      technique for syndactyly release with a hyaluronic acid (HA) scaffold used to
      cover the bare areas is described. Between 2008 and 2011, release of 26 webs in
      23 patients was performed. All skin defects were covered with Hyalomatrix((r))
      PA. One patient was excluded due to early post-operative infection that required
      HA scaffold removal before its integration. Web creep, secondary deformities,
      scar quality, and patient and parental satisfaction were assessed. Mean follow-up
      of the group of 22 patients was 24 months. There were no secondary deformities
      and minimal degree of web creep. All patients had close to normal pigmentation
      and good pliability at the sites of scaffold application. The results confirm the
      use of a HA scaffold as a promising alternative to skin grafting in syndactyly
      release surgery. 

PMID- 24664164
TI  - Study of the outcome of modified shoelace repair for midline incisional hernia.
AB  - AIMS AND OBJECTIVES: To study the efficacy and short-term sequelae of modified
      shoelace repair for midline incisional hernias. MATERIALS AND METHODS: A
      prospective non-randomized study of 30 cases of midline incisional hernias was
      carried out at a public hospital from May 2009 to Oct 2012. Patients underwent
      modified shoelace repair which comprises reconstruction of linea alba along with
      the use of polypropylene mesh to reinforce the facial layer. A proforma was
      maintained for each patient documenting patient details, nature of previous
      surgery and complications if any, postoperative course, and complications
      postincisional hernia repair. RESULTS AND DISCUSSION: Thirty patients underwent
      this repair with no complications and no recurrence for minimum follow-up period
      of 12 months. Our technique is a simple extra-peritoneal procedure with no
      extensive tissue dissection and avoids the potential complications of bowel
      injury and adhesions with the mesh. The principle involved is that during
      straining, the recti shorten by tonic contraction and approximate toward the
      midline. An incisional hernia weakens the midline and causes the recti to move
      laterally with contraction as medial pull is lost. By reforming a strong new
      linea alba, there is restoration of medial pull on recti. This is further
      buttressed by the mesh. CONCLUSION: Modified shoelace repair is a simple and safe
      extra-peritoneal procedure and can be used for all midline incisional hernias.

PMID- 24664165
TI  - Difficult abdominal wall closure: component separation versus partition
      technique.
AB  - BACKGROUND: Partition technique and component separation techniques are natural
      methods of fascia-fascia closure. We present our experiences and research the
      differences between the two techniques. METHODS: From January 2006 to August
      2013, 41 patients with complex abdominal wall defects reconstructed with
      partition (N = 18) or component separation technique (N = 23) alone were enrolled
      into this study. The related data including gender, age, size of defect,
      operation time, hospital stay, duration of follow-up, comorbidities, body mass
      index (BMI) and complications were collected. Nonparametric Mann-Whitney test was
      used to evaluate the differences between the two groups in continuous data; Chi
      square test was used to assess the categorical data. RESULTS: The mean defect
      size of patients with partition technique (N = 18) was 12.55 cm (range 8.2-18.9
      cm) with 148.63 min for average operation time, 8.66 days for hospital stay, and
      28.8 months for mean follow-up. There were nine cases with postoperative
      complications (three cases with skin and soft tissue necrosis; two cases with
      fascia dehiscence; and three cases with wound infection). One case with fascia
      dehiscence suffered from pneumonia simultaneously. Four cases received secondary
      operation (fascia repair and split-thickness skin graft), and the other four
      cases healed spontaneously with mild wound debridement. The mean defect size of
      the patients with component separation (N = 23) technique was 9.45 cm (range 5.7
      12.6 cm) with 143.27 min for average operation time, 7.43 days for hospital stay,
      and 34.33 months for mean follow-up. One case with skin and soft tissue necrosis
      underwent reconstruction with split-thickness skin graft and debridement. Two
      cases with wound infection healed spontaneously with mild wound debridement.
      There were no significant differences in gender, age, operation time, hospital
      stay, duration of follow-up, comorbidities, BMI and long-term postoperative
      complications between the two groups, except for size of defect and short-term
      postoperative complications. CONCLUSIONS: The partition technique could close
      larger abdominal fascia defects than component separation technique, but
      simultaneously run the higher opportunities for short-term postoperative
      complications.

PMID- 24664166
TI  - JC virus in CD34+ and CD19+ cells in patients with multiple sclerosis treated
      with natalizumab.
AB  - IMPORTANCE: Infection with JC virus (JCV) may lead to development of
      demyelinating progressive multifocal leukoencephalopathy in patients with
      multiple sclerosis (MS) who are treated with natalizumab. OBJECTIVE: To determine
      whether mononuclear cells in circulation from MS patients treated with
      natalizumab harbor JCV DNA. DESIGN, SETTING, AND PARTICIPANTS: In this
      prospective investigation, we enrolled 49 MS patients from the Clinical Center
      for Multiple Sclerosis at The University of Texas Southwestern Medical Center and
      18 healthy volunteers. We drew 120-mL blood samples from 26 MS patients at
      baseline and at approximately 3-month intervals to 10 months during the course of
      natalizumab infusions. One blood sample was drawn from 23 MS patients receiving
      natalizumab for more than 24 months and from 18 healthy volunteers.
      INTERVENTIONS: Natalizumab treatment of MS. MAIN OUTCOMES AND MEASURES: The blood
      samples were separated using flow cytometry into CD34+, CD19+, and CD3+ cell
      subsets; DNA templates were prepared using quantitative polymerase chain reaction
      for JCV DNA identification. Plasma samples were tested for anti-JCV antibodies by
      enzyme-linked immunosorbent assays performed at the Laboratory of Molecular
      Medicine and Neuroscience, National Institute of Neurological and Communicative
      Diseases and Stroke. RESULTS: Thirteen of the 26 patients (50%) with baseline and
      follow-up blood samples had detectable viral DNA in at least 1 cell compartment
      at 1 or more points. Ten of the 23 patients (44%) receiving treatment for more
      than 24 months and 3 of the 18 healthy volunteers (17%) also had detectable viral
      DNA in 1 or more cell compartment. Fifteen of the 49 MS patients (31%) were
      confirmed to harbor JCV in CD34+ cells and 12 of 49 (24%) in CD19+ cells. Only 1
      of 18 healthy volunteers were viremic in CD34+ cells and none in CD19+ cells.
      Nine patients and 1 healthy volunteer were viremic but had seronegative test
      results for JCV antibodies. CONCLUSIONS AND RELEVANCE: JC virus DNA was
      detectable within cell compartments of natalizumab-treated MS patients after
      treatment inception and longer. JC virus DNA may harbor in CD34+ cells in bone
      marrow that mobilize into the peripheral circulation at high concentrations.
      Latently infected cells initiate differentiation to CD19+ cells that favors
      growth of JCV. These data link the mechanism of natalizumab treatment with
      progressive multifocal leukoencephalopathy.

PMID- 24664168
TI  - Studies on generalized kinetic model and Pareto optimization of a product-driven
      self-cycling bioprocess.
AB  - The aim of this study is the optimization of a product-driven self-cycling
      bioprocess and presentation of a way to determine the best possible decision
      variables out of a set of alternatives based on the designed model. Initially, a
      product-driven generalized kinetic model, which allows a flexible choice of the
      most appropriate kinetics is designed and analysed. The optimization problem is
      given as the bi-objective one, where maximization of biomass productivity and
      minimization of unproductive loss of substrate are the objective functions. Then,
      the Pareto fronts are calculated for exemplary kinetics. It is found that in the
      designed bioprocess, a decrease of emptying/refilling fraction and an increase of
      substrate feeding concentration cause an increase of the biomass productivity. An
      increase of emptying/refilling fraction and a decrease of substrate feeding
      concentration cause a decrease of unproductive loss of substrate. The preferred
      solutions are calculated using the minimum distance from an ideal solution
      method, while giving proposals of their modifications derived from a decision
      maker's reactions to the generated solutions. 

PMID- 24664167
TI  - Fibroblast-like cells differentiated from adipose-derived mesenchymal stem cells
      for vocal fold wound healing.
AB  - Tissue engineering has revealed the potential to regenerate injured vocal folds,
      and identification of the most suitable seed cells has remained a hot topic of
      research. The aim of this study was to implant fibroblast-like cells
      differentiated from adipose-derived mesenchymal stem cells (ADSCs) in a canine
      acute vocal fold wound model. We then sought to characterize changes in the
      extracellular matrix (ECM) proteins of vocal fold lamina propria. For this
      purpose, ADSCs were induced to differentiate into fibroblasts under the
      regulation of connective tissue growth factor in vitro. Cell surface proteins
      were identified by immunofluorescence staining. Thirty vocal folds of 17 canines
      were injured by localized resection and injected with fibroblast-like cells
      (differentiated ADSCs, dADSCs), ADSCs or vocal fold fibroblasts (VFFs). The
      morphology of vocal folds was observed, and the characteristics of ECM protein
      components (collagen, elastin, hyaluronic acid, decorin and fibronectin) were
      evaluated by immunofluorescence staining from 15 days to 6 months following
      implantation. The results showed that in vitro, the dADSCs showed morphology and
      cell surface protein expression similar to those of VFFs. After implantation in
      vivo, the surfaces of the recipient vocal folds became almost smooth in the
      dADSCs and ADSCs groups at 6 months but remained slightly concave and stiff in
      the VFFs group. The elastin fluorescence intensity increased significantly and
      was maintained at a high level in the dADSCs group. The collagen fluorescence
      intensity increased slightly in the dADSCs and ADSCs groups, whereas it
      demonstrated a more irregular arrangement in the VFFs group. The fluorescence
      intensity of hyaluronic acid, decorin and fibronectin was similar between the
      three implanted groups. These results indicated that dADSCs may confer an
      advantage for vocal fold wound healing. Furthermore, dADSCs have the ability to
      secrete ECM components in vivo, particularly elastin, which may be beneficial for
      vocal fold vibration recovery. 

PMID- 24664169
TI  - Noninvasive and automatic diagnosis of patients at high risk of swallowing
      aspiration.
AB  - Swallowing aspiration is known as the most clinically significant symptom of
      swallowing disorders (dysphagia). Noninvasive methods for detection of aspiration
      (the entry of food into airway due to dysphagia) are of great interest as they
      will lead to better management of dysphagia; thus, the risk of pneumonia, length
      of hospital stay and overall health care expenses can be reduced. The risk of
      aspiration is much higher in severely dysphagic patients. Normally, aspiration is
      detected by an imaging technique during swallowing, which is time consuming,
      costly and requires the patient's cooperation. In this study, we investigated the
      application of acoustical analysis of breathing and swallowing sounds for
      identifying patients at high risk of aspiration. We propose a novel method based
      on phase-space analysis of breathing sounds immediately after the swallow
      followed by support vector machine classification for use as a diagnostic aid for
      identifying patients with high risk of aspiration. We evaluated the method using
      breath and swallowing sounds recorded from 50 dysphagic individuals, 27 of which
      demonstrated silent aspiration (without cough or throat clearance) during either
      fiberoptic endoscopic evaluation of swallowing (FEES) or videofluoroscopic
      swallowing (VFS) assessment. The classification result of the proposed method was
      compared with those of the FEES/VFS assessment provided by speech-language
      pathologists; it showed 91 % sensitivity and 85 % specificity in detection of
      patients with severe aspiration (high risk dysphagia). The result is promising to
      suggest the proposed phase-space acoustical analysis method as a quick and
      noninvasive screening clinical tool to detect patients developing severe
      aspiration. 

PMID- 24664170
TI  - Islamic bioethical deliberation on the issue of newborns with disorders of sex
      development.
AB  - This article presents the Islamic bioethical deliberation on the issue of sex
      assignment surgery (SAS) for infants with disorders of sex development (DSD) or
      intersexed as a case study. The main objective of this study is to present a
      different approach in assessing a biomedical issue within the medium of the
      Maqasid al-Shari'ah. Within the framework of the maqasidic scheme of benefits and
      harms, any practice where benefits are substantial is considered permissible,
      while those promoting harms are prohibited. The concept of Maqasid al-Shari'ah
      which is the mechanistic interpretation of Qur'an and Hadith presents the
      holistic attention of Islam on many life activities, including healthcare.
      Indeed, this concept encompasses many aspects of worldly life, both for the human
      individual and collectively for the whole society. In healthcare, the practice of
      SAS on DSD newborns has presented an assortment of implications on the future
      livelihood of the affected individual. The process of decision-making seems to be
      very multifaceted since every element such as the determination of the 'correct'
      sex and the urgency of early surgery must consider the benefits and harms, as
      well as the child's rights and best interest. The application of the concept of
      Maqasid al-Shari'ah, would convey a pragmatic approach that is often disregarded
      in Western medicine. This approach considers the right of the individual to live
      life optimally, individually and socially and practice his faith, precisely, in
      accordance with the assigned gender. 

PMID- 24664171
TI  - HIV-1 infection impairs regulatory T-cell suppressive capacity on a per-cell
      basis.
AB  - The impact of CD4+ regulatory T cells (Tregs) on human immunodeficiency virus
      type 1 (HIV-1) pathogenesis remains incompletely understood. Although it has been
      shown that Tregs can be infected with HIV-1, the consequences of infection on a
      per-cell basis are still unknown. In vitro HIV-GFP infected and noninfected Tregs
      were isolated by flow-based cell-sorting to investigate Treg suppressive capacity
      and gene expression profiles. Our data show that HIV-1-infected Tregs were
      significantly less suppressive than noninfected Tregs and demonstrated down
      regulation of genes critical to Treg function. This impaired function may have
      detrimental consequences for the control of generalized immune activation and
      accelerate HIV disease progression.

PMID- 24664172
TI  - Valacyclovir therapy does not reverse herpes-associated alterations in cervical
      immunology: a randomized, placebo-controlled crossover trial.
AB  - Herpes simplex virus type 2 (HSV-2) infection is associated with a 3-fold
      increase in the risk of human immunodeficiency virus (HIV) acquisition, perhaps
      through alterations in mucosal HIV-susceptible target cells. We performed a
      clinical trial to assess the impact of herpes therapy on cervical immunology in
      HSV-2-infected, HIV-uninfected women from Africa or the Caribbean who were living
      in Toronto, Canada. Thirty participants received 1 g of valacyclovir orally each
      day for 2 months in a randomized double-blind, placebo-controlled, crossover
      trial. Valacyclovir did not reduce the number of cervical CD4(+) T cells, the
      number of dendritic cells, or the expression of proinflammatory cytokines and
      tended to increase the expression of the HIV coreceptor CCR5 and the activation
      marker CD69. Short-term valacyclovir therapy did not reverse HSV-2-associated
      alterations in genital immunology. Clinical Trials Registration. NCT00946556. 

PMID- 24664173
TI  - Immune profiling of pregnant Toxoplasma-infected US and Colombia patients reveals
      surprising impacts of infection on peripheral blood cytokines.
AB  - In North America (NA) and Europe, the majority of toxoplasmosis cases are benign
      and generally asymptomatic, whereas in South America (SA) toxoplasmosis is
      associated with much more severe symptoms in adults and congenitally infected
      children. The reasons for these differences remain unknown; currently, there is
      little information from patients in either region on how the immune system
      responds to infection with Toxoplasma gondii. Here, we report the relative
      abundance of 51 serum cytokines from acute and chronic toxoplasmosis cohorts of
      pregnant women from the United States, where approximately one-half of clinical
      isolates are Type II, and Colombia, where clinical isolates are generally
      "atypical" or Type I-like strains. Surprisingly, the results showed notably lower
      levels of 23 cytokines in acutely infected patients from the United States,
      relative to uninfected US controls. In acutely infected Colombian patients,
      however, only 8 cytokine levels differed detectably with 4 being lower and 4
      higher relative to uninfected controls. Strikingly, there were also differences
      in the cytokine profiles of the chronically infected patients relative to
      uninfected controls in the US cohort. Hence, Toxoplasma appears to specifically
      impact levels of circulating cytokines, and our results may partly explain region
      specific differences in the clinical spectrum of toxoplasmosis. 

PMID- 24664174
TI  - X-ray dose reduction in abdominal computed tomography using advanced iterative
      reconstruction algorithms.
AB  - OBJECTIVE: This work aims to explore the effects of adaptive statistical
      iterative reconstruction (ASiR) and model-based iterative reconstruction (MBIR)
      algorithms in reducing computed tomography (CT) radiation dosages in abdominal
      imaging. METHODS: CT scans on a standard male phantom were performed at different
      tube currents. Images at the different tube currents were reconstructed with the
      filtered back-projection (FBP), 50% ASiR and MBIR algorithms and compared. The CT
      value, image noise and contrast-to-noise ratios (CNRs) of the reconstructed
      abdominal images were measured. Volumetric CT dose indexes (CTDIvol) were
      recorded. RESULTS: At different tube currents, 50% ASiR and MBIR significantly
      reduced image noise and increased the CNR when compared with FBP. The minimal
      tube current values required by FBP, 50% ASiR, and MBIR to achieve acceptable
      image quality using this phantom were 200, 140, and 80 mA, respectively. At the
      identical image quality, 50% ASiR and MBIR reduced the radiation dose by 35.9%
      and 59.9% respectively when compared with FBP. CONCLUSIONS: Advanced iterative
      reconstruction techniques are able to reduce image noise and increase image CNRs.
      Compared with FBP, 50% ASiR and MBIR reduced radiation doses by 35.9% and 59.9%,
      respectively.

PMID- 24664175
TI  - Radiographic and ultrasonographic changes of the patellar ligament following
      tibial tuberosity advancement in 25 dogs.
AB  - INTRODUCTION: Patellar ligament thickening is a recognized response following
      osteotomy of the proximal tibia as a treatment for cranial cruciate disease. In
      humans this is seen as a response to increased loading, but the reason for this
      thickening in dogs is unclear. A prospective study was undertaken to assess the
      degree and frequency of patellar ligament desmopathy in 25 consecutive cases
      undergoing tibial tuberosity advancement (TTA). OBJECTIVES: To determine the
      incidence of patellar ligament thickening following TTA. METHODS: Consecutive
      cases undergoing TTA had ultrasonographic and radiographic measurements performed
      of the patellar ligament, at multiple positions on the ligament. This was
      performed at the time of surgery, and at six weeks and six months (ultrasound
      only) following surgery. The radiographic measurements were performed by two
      reviewers who were blinded to the timeframe of each image. RESULTS: There was
      great variation in both the incidence and degree of thickening of the ligament.
      Fifty percent of the cases showed no changes in the thickness of the patellar
      ligament. A clinical pain response was not associated with patellar ligament
      thickening. No statistically significant variables which predicted the
      development of patellar ligament thickening were identified . CLINICAL
      SIGNIFICANCE: The presence of signs of patellar ligament thickening is of
      questionable clinical significance and is probably an incidental finding.

PMID- 24664176
TI  - Chitinases are negative regulators of Francisella novicida biofilms.
AB  - Biofilms, multicellular communities of bacteria, may be an environmental survival
      and transmission mechanism of Francisella tularensis. Chitinases of F. tularensis
      ssp. novicida (Fn) have been suggested to regulate biofilm formation on chitin
      surfaces. However, the underlying mechanisms of how chitinases may regulate
      biofilm formation are not fully determined. We hypothesized that Fn chitinase
      modulates bacterial surface properties resulting in the alteration of biofilm
      formation. We analyzed biofilm formation under diverse conditions using chitinase
      mutants and their counterpart parental strain. Substratum surface charges
      affected biofilm formation and initial attachments. Biophysical analysis of
      bacterial surfaces confirmed that the chi mutants had a net negative-charge.
      Lectin binding assays suggest that chitinase cleavage of its substrates could
      have exposed the concanavalin A-binding epitope. Fn biofilm was sensitive to
      chitinase, proteinase and DNase, suggesting that Fn biofilm contains
      exopolysaccharides, proteins and extracellular DNA. Exogenous chitinase increased
      the drug susceptibility of Fn biofilms to gentamicin while decreasing the amount
      of biofilm. In addition, chitinase modulated bacterial adhesion and invasion of
      A549 and J774A.1 cells as well as intracellular bacterial replication. Our
      results support a key role of the chitinase(s) in biofilm formation through
      modulation of the bacterial surface properties. Our findings position chitinase
      as a potential anti-biofilm enzyme in Francisella species. 

PMID- 24664177
TI  - Reduced pleasant touch appraisal in the presence of a disgusting odor.
AB  - OBJECTIVES: Odors are powerful emotional stimuli influencing mood, attention and
      behavior. Here we examined if odors change the perception of pleasant touch. In
      line with the warning function of the olfactory system, we proposed that
      especially unpleasant odors will reduce touch pleasantness, presumably through a
      disgust-related mechanism. METHODS: Forty-five healthy participants (mean age
      23.3 +/- 3years SD, 24 females) were presented to slow (3 cm/s) and fast (30
      cm/s) brush stroking delivered by a robot to the forearm. Touch pleasantness
      under the influence of an unpleasant odor (Civette, smelling like feces) and an
      intensity matched pleasant odor (Rose) was compared to an odorless control
      condition. In a pilot study with 30 participants (mean age 25.9 +/-6 years, 21
      females), the odors were matched according to their intensity, and we studied the
      influence of disgust sensitivity on the perception of 4 different odor qualities.
      RESULTS: The unpleasant odor decreased touch pleasantness for both stroking
      velocities compared to the odorless control (p<0.005) whereas the rose odor did
      not change touch pleasantness significantly. Disgust sensitivity was correlated
      with the modulation of touch pleasantness. The pilot study revealed a significant
      correlation between disgust sensitivity and the perception of the unpleasant odor
      qualities (r = -0.56; p = 0.007), but not with any of the other odors.
      CONCLUSION: Unpleasant odors are powerful in modulating touch pleasantness, and
      disgust might be a moderating variable.

PMID- 24664178
TI  - Changes in metal mobility associated with bark beetle-induced tree mortality.
AB  - Recent large-scale beetle infestations have caused extensive mortality to conifer
      forests resulting in alterations to dissolved organic carbon (DOC) cycling, which
      in turn can impact metal mobility through complexation. This study analyzed soil
      water samples beneath impacted trees in concert with laboratory flow-through soil
      column experiments to explore possible impacts of the bark beetle infestation on
      metal release and transport. The columns mimicked field conditions by introducing
      pine needle leachate and artificial rainwater through duplicate homogenized soil
      columns and measuring effluent metal (focusing on Al, Cu, and Zn) and DOC
      concentrations. All three metals were consistently found in higher concentrations
      in the effluent of columns receiving pine needle leachate. In both the field and
      laboratory, aluminum mobility was largely correlated with the hydrophobic
      fraction of the DOC, while copper had the largest correlation with total DOC
      concentrations. Geochemical speciation modeling supported the presence of DOC
      metal complexes in column experiments. Copper soil water concentrations in field
      samples supported laboratory column results, as they were almost twice as high
      under grey phase trees than under red phase trees further signifying the
      importance of needle drop. Pine needle leachate contained high concentrations of
      Zn (0.1 mg l(-1)), which led to high effluent zinc concentrations and sorption of
      zinc to the soil matrix representing a future potential source for release. In
      support, field soil-water samples underneath beetle-impacted trees where the
      needles had recently fallen contained approximately 50% more zinc as samples from
      under beetle-impacted trees that still held their needles. The high
      concentrations of carbon in the pine needle leachate also led to increased
      sorption in the soil matrix creating the potential for subsequent carbon release.
      While unclear if manifested in adjacent surface waters, these results demonstrate
      an increased potential for Zn, Cu, and Al mobility, along with increased
      deposition of metals and carbon beneath beetle-impacted trees. 

PMID- 24664179
TI  - The nature of the control of blood glucose in those with poorer glucose tolerance
      influences mood and cognition.
AB  - The ability to control the levels of blood glucose was related to mood and
      cognition. 155 adults, aged 45-85 years, without a diagnosis of diabetes, were
      given an oral glucose tolerance test and cognitive tests. Participants were
      classified according to age (41-60/61-85 years), whether they had better or
      poorer glucose tolerance and whether blood glucose did or did not fall below
      baseline values. There were two main findings. Those with poorer glucose
      tolerance forgot more words and had slower decision times, but only if 61 years
      or older. Secondly as there are reports in animal studies that inducing low
      levels of blood glucose values benefited cognitive performance, for the first
      time in humans, individual differences in the tendency to develop low levels of
      blood glucose were considered. In those with poor glucose tolerance a tendency
      for blood glucose to fall below baseline values was associated with better mood
      and faster working memory.

PMID- 24664180
TI  - Brain metabolite clearance: impact on Alzheimer's disease.
AB  - Alzheimer's Disease (AD) is a complex neurodegenerative disorder often associated
      with aging and characterized by several critical molecular changes that take
      place in the brain. Among the molecular hallmarks of AD, increased levels of
      amyloid beta-peptide (Abeta) and the subsequent Abeta-derived damage are the most
      well-studied factors; however, despite the large amounts of effort and resources
      devoted to the study of AD and AD pathophysiology, the scientific community still
      awaits therapeutic alternatives capable of ensuring a better outcome for AD
      patients. In 2012, Cramer et al. (Science 335:1503-1506 2012) astonished the
      scientific community by rescuing behavioral and cognitive impairments in AD mouse
      models via oral administration of bexarotene, a drug used to treat some types of
      skin cancer. Moreover, these authors demonstrated that bexarotene, a retinoid X
      receptor (RXR) agonist, exerts major effects on Abeta levels, mainly through
      increased apolipoprotein E (ApoE) expression. Apart from the valid questions
      addressed in Cramer's work, only a few attempts have been made to explain the
      effects of bexarotene. Most of these explanations have been solely based on the
      ability of bexarotene to reduce Abeta levels and not on the mechanisms that lead
      to such a reduction. Although it is well known that an imbalance in the Abeta
      production/excretion rate is the basis of increased Abeta levels in AD, no
      further explanations have been proposed to address the potential involvement of
      the blood-brain barrier (BBB), a critical Abeta-clearance structure, in the
      bexarotene-mediated effects. Moreover, no attempt has been made to explain how
      the different effects observed after bexarotene administration are connected to
      each other. Based on current information and on our own experience with nuclear
      receptors (NR), we offer new perspectives on the mechanisms of bexarotene action,
      which should help to improve our knowledge of NRs. 

PMID- 24664181
TI  - Additive effects of maternal high fat diet during lactation on mouse offspring.
AB  - Recent reports indicated that nutrition in early infancy might influence later
      child health outcomes such as obesity and metabolic syndrome. Therefore, we
      examined the effects of maternal high fat diet (HFD) during lactation on the
      onset of a metabolic syndrome in their offspring. All offspring were cross
      fostered by dams on the same or opposite diet to yield 4 groups: offspring from
      HFD-fed dams suckled by HFD-fed dams (OHH) and by control diet (CD)-fed dams
      (OHC) and CD-fed dams suckled by HFD-fed dams (OCH) and by CD-fed dams (OCC)
      mice. We examined several metabolic syndrome-related factors including body
      weight, blood pressure, glucose tolerance and adipocytokines. Mean body weights
      of OHH and OCH mice were significantly higher than those of OHC and OCC mice,
      respectively, with elevated systolic blood pressure. Moreover, OHH and OCH mice
      revealed significantly worse glucose tolerance compared with the OHC and OCC
      mice, respectively. Triglyceride and leptin levels were significantly increased
      and adiponectin levels were significantly reduced by the maternal HFD during
      lactation, with similar changes in leptin and adiponectin mRNA expression but
      without histone modifications in adipose tissues. In addition, maternal obesity
      induced by HFD during lactation increased and prolonged the leptin surge in the
      offspring and the gender differences of leptin surge were observed. Our data
      suggested that maternal HFD during lactation might have an additive effect on the
      onset of the metabolic syndrome in the offspring, irrespective of the nutritional
      status in utero through the modified leptin surge. 

PMID- 24664182
TI  - New combinational assay using soluble fibrin and d-dimer determinations: a
      promising strategy for identifying patients with suspected venous
      thromboembolism.
AB  - AIM: To establish a new and reliable assay for quantification of the soluble
      fibrin (SF) in combination with that of D-dimer for early diagnosis of venous
      thromboembolism. METHODS AND SAMPLES: The SF assay is based on D-dimer generated
      after incubation of plasma with tissue-type plasminogen activator (t-PA). SF and
      standard D-dimer assays, run in blind, were used to test 119 untreated
      outpatients with clinically suspected deep-vein thrombosis (DVT, 49 patients) or
      pulmonary embolism (PE, 70 patients) consulting at the emergency unit of the
      hospital. Thromboses were confirmed by current imaging methods such as
      ultrasonography, scintigraphy, computed tomographic pulmonary angiography (CTPA)
      and ventilation/perfusion scan. RESULTS: SF assay was validated in 270 healthy
      volunteers [51.8% males; mean age years +/- SD: 41+/-13; age range 19 to 65].
      Among these normal plasmas, SF levels were <=200 ng/mL in 97.8% of them, and 200
      250 ng/mL in the remainder [26-46 years old; 50% males]. ROC curves were used to
      determine the SF cut-off value for plasma SF positivity, which was found to be
      300 ng/mL. In patients with suspected venous thromboembolism, SF sensitivities
      for DVT and PE (92% and 94%, respectively) were comparable to those of D-dimer
      (96% and 94%), whereas SF specificities (86% and 95%) were higher than those of D
      dimer (50% and 54%). Positive-predictive values for SF (89% and 94%) were again
      higher than those of D-dimer (70% and 65%) in DVT and PE. The amount of
      circulating SF normalized rapidly after anticoagulant therapy. CONCLUSION:
      Results from this small group of patients suggest that the evaluation of plasma
      SF, in combination with that of D-dimer, represents a potentially useful tool for
      the early diagnosis of venous thromboembolism, provided that the patients have
      not been treated previously by anticoagulants.

PMID- 24664183
TI  - Bioorthogonal site-specific labeling of the 5'-cap structure in eukaryotic mRNAs.
AB  - We present a chemo-enzymatic approach for site-specific labeling of 5'-capped
      RNAs based on bioorthogonal chemistry. A trimethylguanosine synthase was
      engineered to transfer a terminal azido moiety to the 5'-cap which could be
      further modified using strain-promoted azide-alkyne cycloaddition (SPAAC). 

PMID- 24664184
TI  - Graphene oxide and shape-controlled silver nanoparticle hybrids for
      ultrasensitive single-particle surface-enhanced Raman scattering (SERS) sensing.
AB  - Graphene oxide (GO) is an emerging material for surface-enhanced Raman scattering
      (SERS) due to its strong chemical enhancement. Studying the SERS performance of
      plasmonic nanoparticle/GO hybrid materials at the single particle level is
      crucial for direct probing of the chemical effect of GO on plasmonic
      nanoparticles. In this work, we integrate GO and shape-controlled Ag
      nanoparticles to create hybrid nanomaterials, and the chemical enhancement
      arising from GO is investigated using single-particle SERS measurements. Ag
      nanoparticle@GO hybrid nanostructures are prepared by assembling Ag
      nanoparticles, including spheres, cubes and octahedra with GO sheets. The SERS
      behaviors of the hybrid nanostructures are characterized, and 2-3 times enhanced
      SERS intensities are detected from the Ag nanoparticle@GO hybrid nanostructures
      as compared to pure Ag nanoparticles. Furthermore, we probe the mechanism of SERS
      enhancement in the hybrid nanostructures by changing the surface coverage of GO
      on Ag octahedra, by using reduced GO in place of GO as well as by using probe
      molecules of different electronegativities. This hybrid system is an excellent
      candidate for single-particle SERS sensors. Sub-nanomolar levels of aromatic
      molecules are detected using a single Ag/GO hybrid nanomaterial. This as-prepared
      GO and shape-controlled Ag nanoparticle hybrid is capable of serving as a high
      performance SERS platform, providing new opportunities for efficient chemical and
      biological sensing applications. 

PMID- 24664185
TI  - Intra-articular zoledronic acid in a rat osteoarthritis model: significant
      reduced synovitis may indicate chondroprotective effect.
AB  - PURPOSE: The aim of this experimental study was to evaluate the effect of intra
      articular application of zoledronic acid (ZA) on joint cartilage and synovial
      tissue following induction of knee osteoarthritis (OA) in a rat model. METHODS:
      An OA model was created by anterior cruciate ligament transection (ACLT) in the
      right knees of 48 adult Wistar albino rats. The rats were randomized into a study
      and control groups, each including 24 rats, and 10 MUg of ZA was injected in 0.1
      ml of sterile saline to 24 animals in the study group on the first day to
      operation and was repeated weekly until the rats were killed. The same volume of
      sterile saline was injected with the same schedule to the control group. Eight
      rats from both the study and control groups were killed, each time, on the 4th
      day, the 3rd week, and the 6th week after the operation. The groups were compared
      based on the histological scores of synovitis and cartilage destruction and the
      evaluation of serum markers. RESULTS: Histological score indicates progression of
      synovitis was significantly less in the study group (p = 0.047). There was
      significant increase in the mean Mankin cartilage damage score in the control
      group (p = 0.021), while no significant change was found in the study group. When
      the two groups were compared over time, no statistically significant difference
      was detected in total histological scores, although there was a 47 % less
      incidence of cartilage tissue damage in the study group and better cartilage
      structure and tide mark integrity scores were also detected in the study group (p
      = 0.017 and p = 0.021, respectively). CONCLUSION: Intra- articular zoledronic
      acid may suppress synovial inflammation. Furthermore, Zoledronic Acid does not
      reduce cartilage degeneration in early osteoarthritis models, but may provide
      some chondroprotective effect in ACLT- induced knee osteoarthritis model in rats.

PMID- 24664186
TI  - Using fibula as a reference can be beneficial for the tibial component alignment
      after total knee arthroplasty, a retrospective study.
AB  - PURPOSE: One of the important factors in a successful arthroplasty is component
      alignment. The primary objective of this study was to determine whether the
      fibular shaft reference technique is beneficial for the tibial component position
      on the postoperative plain radiograph after total knee arthroplasty. METHODS: A
      total of 42 patients between 2009 and 2011 were analysed retrospectively. The
      surgeon prepared the tibia using an extramedullary cutting guide and set the
      posterior tibial slope with respect to the fibular reference rod. In the
      postoperative radiographic measurements, a true anteroposterior and lateral
      radiograph of the lower leg covering the whole length of the tibia was used.
      RESULTS: Five patients were excluded as they did not meet the inclusion criteria,
      four patients were excluded due to improper radiographs and the study group was
      reduced to 33 patients and 35 knees. The mean preoperative tibiofibular angle was
      2.1 degrees  +/- 0.8 degrees . The mean postoperative tibial sagittal angle
      measurements were 83.3 degrees  +/- 1.4 degrees  (81 degrees -86 degrees ). 33
      (94 %) Knees gained the desired tibial sagittal angle within the desired
      alignment (5 degrees  +/- 3 degrees ). The mean postoperative tibial coronal
      angle was 89.3 degrees  +/- 1.5 degrees . The tibial component coronal angle of
      two knees was more than 3 alignment from the neutral mechanical axis. CONCLUSION:
      The major clinical relevance of the technique described in the present study is
      cost-effectiveness, and it does not require any extra time or surgical equipment.
      This method can be used as an alternative choice for bulky extremities which is a
      cause of malalignment of the components. LEVEL OF EVIDENCE: Retrospective case
      series, Level IV.

PMID- 24664187
TI  - Subcutaneous trastuzumab: a review of its use in HER2-positive breast cancer.
AB  - Trastuzumab (Herceptin(r)) is a humanized IgG1 monoclonal antibody that is an
      efficacious treatment for HER2-positive breast and gastric cancers. Subcutaneous
      trastuzumab is a new formulation approved in the European Union for use in
      patients with early or metastatic breast cancer. In the randomized, open-label,
      multinational HannaH (enHANced treatment with NeoAdjuvant Herceptin) study of
      neoadjuvant/adjuvant trastuzumab in patients with early HER2-positive breast
      cancer, the pharmacokinetics of neoadjuvant subcutaneous trastuzumab were similar
      to those after intravenous administration, meeting the noninferiority criterion
      for mean predose trough concentrations, as assessed prior to surgery (primary
      pharmacokinetic endpoint). Trastuzumab blood concentrations throughout the dosing
      interval remained above those considered necessary for anticancer activity. In
      this study, the pathologic complete response rates (primary efficacy endpoint)
      were 45.4 and 40.7 % in the subcutaneous and intravenous administration groups,
      respectively, meeting a study noninferiority criterion. In the randomized, open
      label, crossover, multinational PrefHer study of neoadjuvant/adjuvant or adjuvant
      trastuzumab in early HER2-positive breast cancer, subcutaneous administration of
      trastuzumab was preferred over intravenous administration by >85 % of patients,
      most commonly because it was time saving and induced less pain and discomfort. In
      the HannaH study, the tolerability profile of subcutaneous trastuzumab was
      similar to that of intravenous trastuzumab, except that the rate of serious
      adverse events was 21 % (vs. 12 % with intravenous administration), partly
      because of more infections with subcutaneous administration. Whether this finding
      is of any clinical significance should emerge from ongoing studies. On the
      evidence, subcutaneous trastuzumab is an effective and generally well-tolerated
      treatment option that is preferred by patients over intravenous administration. 

PMID- 24664188
TI  - Dietary energy density is associated with obesity and other biomarkers of chronic
      disease in US adults.
AB  - PURPOSE: Given the current prevalence of obesity, it is important to identify
      dietary factors that may aid in disease prevention. The objective of the present
      study was to evaluate the association between consumption of an energy-dense diet
      and established markers factors for chronic disease, including body weight and
      measures of body fatness. METHODS: Data from a nationally representative sample
      of 9,551 adults >=18 years who participated in the 2005-2008 National Health and
      Nutrition Examination Survey were analyzed. The association between dietary
      energy density (ED, energy per weight of food, kcal/g) and markers for obesity
      [including body mass index (BMI) and waist circumference (WC)], insulin
      insensitivity [including fasting glucose, insulin and homeostasis assessment
      model for insulin resistance (HOMA-IR)], and markers for inflammation was
      examined. RESULTS: Dietary ED was positively associated with obesity in both men
      and women in multivariate models. Overall, obese adults had a significantly
      higher dietary ED than lean adults (p < 0.0001). Current smokers had
      significantly higher ED than non-smokers (2.00 vs. 1.75, p < 0.01), and it was
      determined that smoking status modified the relationship between ED and weight
      status in women (p interaction 0.03). In both sexes, there was a positive linear
      relationship between BMI and ED (p trend 0.01 and 0.0002, respectively); a linear
      trend between WC and ED was also observed in women (p trend <0.001) after
      adjusting for relevant cofactors. In women, ED was positively associated with
      HOMA-IR and fasting insulin; though, this relationship was not observed in men.
      No significant associations between ED and C-reactive protein were observed in
      either sex. CONCLUSION: These findings support recent obesity and disease
      prevention recommendations to consume a diet low in ED.

PMID- 24664189
TI  - Long-term adherence to the New Nordic Diet and the effects on body weight,
      anthropometry and blood pressure: a 12-month follow-up study.
AB  - PURPOSE: The New Nordic Diet (NND) has induced weight loss in a 26-week
      controlled intervention. We aim to investigate whether high compliance and
      satisfaction can be maintained after the active intervention is discontinued
      thereby maintaining the health effects. METHODS: After 26 weeks of intervention
      with NND or Average Danish Diet (ADD), 147 participants (mean age 43 years and
      mean BMI 29.1 kg/m2) were followed for further 52 weeks. All participants were
      encouraged to follow NND but without further guidance. The study is registered
      with ClinicalTrials.gov, study id NCT01195610. RESULTS: One hundred and ten
      participants (75%) completed the follow-up. Among participants previously
      randomised to NND (NND group), dietary compliance and satisfaction decreased from
      4.3 to 3.0 and from 4.8 to 4.0, respectively (both p < 0.0001) (1-5 point scale).
      Among those originally randomised to ADD (ADD group), satisfaction with NND was
      significantly higher than with ADD during follow-up (3.3 vs. 2.5, p = 0.026).
      Weight losses during intervention of -6.2 kg and -3.0 kg were followed by regains
      of 4.6 kg (SE 0.5) and 1.1 kg (SE 0.7) for the NND group and ADD group,
      respectively [adjusted difference; mean (95 % CI): 1.8 kg (0.1-3.4), p = 0.041].
      Across diet groups, every 1 score higher in compliance with NND was associated
      with 0.90 kg less body weight regain (p = 0.026) and those who increased physical
      activity regained 3.4 kg less compared to those who did not (p < 0.0001).
      CONCLUSIONS: NND provides higher satisfaction, and body weight regain is reduced
      with higher compliance with NND and increased physical activity.

PMID- 24664191
TI  - Neurological involvement in children with E. coli O104:H4-induced hemolytic
      uremic syndrome.
AB  - BACKGROUND: The aim of this study was to analyze the neurological involvement and
      outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the
      2011 epidemic caused by Escherichia coli O104:H4. METHODS: Clinical data and data
      from magnetic resonance imaging (MRI) scans and electroencephalography (EEG)
      during the acute phase of the disease and during follow-up at 3 and 6 months were
      analyzed in 50 patients. Twenty-five of these patients underwent
      neuropsychological testing (WISC IV) during follow-up. RESULTS: Neurological
      involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni)
      was initially observed in 14/50 (28%) patients. One patient died. EEG
      abnormalities were more frequent in patients with neurological involvement than
      in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed
      in nine patients with neurological involvement, of whom five showed abnormal
      findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40
      (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%)
      patients, respectively, complained about on-going reduced performance.
      Neuropsychological testing showed a slightly lower global intelligence quotient
      in patients with neurological involvement versus those without (113.4 +/- 2.8 vs.
      119.4 +/- 1.8, respectively). CONCLUSIONS: Neurological involvement was frequent
      in our cohort. Accordingly, the incidence of pathological EEG findings was high,
      even in patients without clinical signs of neurological involvement.
      Nevertheless, major neurological sequelae were rare, and neuropsychological
      outcome was favorable after 6 months.

PMID- 24664192
TI  - MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in
      dogs.
AB  - OBJECTIVES: To measure the activity of matrix metalloproteinases (MMP)-2 and -9
      in synovial fluid from the stifle joints of dogs with cranial cruciate ligament
      (CrCL) rupture and to compare that to values from contralateral stifle joints and
      dogs with clinically normal stifle joints. Additionally, the C-reactive protein
      (CRP) levels were also measured. METHODS: Fourteen large breed dogs with
      unilateral CrCL rupture and 11 large breed normal dogs were included in this
      prospective clinical study. Synovial fluid was collected from CrCL-ruptured
      stifle joints, contralateral clinically normal stifle joints of the same dogs,
      and stifle joints of normal dogs. Serum was also collected. Synovial fluid
      activities of MMP-2 and MMP-9 and serum CRP level were measured. RESULTS: The MMP
      2 activity in synovial fluid was significantly higher in CrCL-ruptured joints
      compared to contralateral joints and to stifles from normal dogs. There was no
      significant difference in activity of MMP-2 in contralateral joints of CrCL
      ruptured dogs compared to normal dogs. Both serum CRP level and MMP-9 activity
      did not differ significantly between the studied conditions. CLINICAL
      SIGNIFICANCE: It was confirmed that MMP-2 activity is significantly related to
      CrCL rupture, but there was a failure to demonstrate any significant increase in
      the contralateral joints compared to the stifle joints of normal dogs. The MMP-2
      involvement in progressing CrCL disease still has to be defined.

PMID- 24664193
TI  - Frequent complications and severe bone loss associated with the repiphysis
      expandable distal femoral prosthesis.
AB  - BACKGROUND: The treatment of choice for distal femur malignancies in skeletally
      immature patients remains controversial. An expandable endoprosthesis device
      (Repiphysis Limb Salvage System; Wright Medical Technology, Arlington, TN, USA)
      allows for limb preservation and noninvasive lengthening but has been associated
      with significant complications; however, the extent and implications of bone loss
      associated with this implant have not been reported. QUESTIONS/PURPOSES: Our
      goals were to report (1) the 2-year minimum clinical outcomes after placement of
      the Repiphysis expandable prosthesis for pediatric distal femur malignancies; (2)
      the complications associated with this prosthesis; (3) the failure rate of this
      prosthesis; and (4) the revision alternatives available for salvage procedures.
      METHODS: Between 2002 and 2010, one surgeon (SG) treated all skeletally immature
      patients (mean age, 10.1 years; range, 4.7-13.6 years) with distal femoral
      osteosarcoma using a Repiphysis expandable prosthesis. Of the 12 patients who met
      these criteria, two were excluded for death from disease before 2 years, and mean
      followup for the remaining 10 was 72 months (range, 26-119 months). Medical
      records were retrospectively reviewed for complications and clinical outcomes, as
      assessed by the Musculoskeletal Tumor Society (MSTS) scoring system. Radiographs
      at final followup were reviewed for bone loss and analyzed by the two senior
      authors (SG, WWV) to determine reconstruction options available for future
      revisions. RESULTS: MSTS scores averaged 67%, and we observed 37 implant-related
      complications requiring a total of 15 reoperations. Six patients underwent
      implant revisions with aseptic loosening being the predominant mode of failure;
      ultimately, four of these were converted to adult modular oncology prostheses,
      and two underwent total femoral replacements. Bone loss in this series was severe
      in terms of femoral length, cortical thinning, and metadiaphyseal compromise, and
      most patients will not have sufficient bone stock to permit future revision using
      standard stem fixation. CONCLUSIONS: The bone loss around the stem of this
      prosthesis limits subsequent revision options, often resulting in a total femoral
      prosthesis. Although the decision to use the Repiphysis device must be made on an
      individual basis, surgeons should recognize the potential for significant bone
      compromise limiting revision options and consider other options. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 24664194
TI  - Internal lengthening device for congenital femoral deficiency and fibular
      hemimelia.
AB  - BACKGROUND: Patients with congenital limb shortening can present with joint
      instability, soft tissue contractures, and significant leg length discrepancy.
      Classically, lengthening is done with external fixation, which can result in
      scarring, pin site infection, loss of motion, and pain. We therefore developed an
      alternative to this approach, a new, controllable, internal lengthening device
      for patients with congenital limb shortening. QUESTIONS/PURPOSES: We evaluated
      this device in terms of (1) healing index, (2) complications, (3) accuracy of the
      device's external controller, and (4) adjacent-joint ROM. METHODS: Between
      January 2012 and May 2013, we treated 66 patients for congenital limb shortening,
      of whom 21 were treated using this device. During this period, general
      indications for using the device were patients with leg length discrepancies of 2
      cm or more, with intramedullary canals able to withstand rods of at least 12.5-mm
      diameter and 230-mm length, without active infection in the affected bone, able
      to comply with the need for frequent lengthening, and without metal allergies or
      an implanted pacemaker. We included only those patients who had completed their
      course of treatment and were currently fully weightbearing, leaving 18 patients
      (21 bone segments) available for followup at a minimum of 6 months after limb
      lengthening (mean, 14 months; range, 6-22 months). Mean age was 19 years (range,
      9-49 years). Sixteen femurs and five tibias were lengthened a mean of 4.4 cm
      (range, 2.1-6.5 cm). Mean distraction index was 1.0 mm/day (range, 0.5-1.8
      mm/day). Healing index, complications, device accuracy, and ROM were recorded. To
      date, 10 of the 21 devices have been removed. This was typically done 12-24
      months after insertion when the bone was solidly healed on all four cortices.
      RESULTS: Mean healing index was 0.91 months/cm (range, 0.2-2.0 months/cm). There
      were seven complications requiring an additional unplanned surgery, including one
      hip flexion contracture, three femurs with delayed healing, one tibia with
      delayed healing, one hip subluxation/dislocation, and one knee subluxation. The
      external controller was accurate as programmed and actual lengthening amounts
      were consistent. ROMs of the hip, knee, and ankle were essentially maintained.
      CONCLUSIONS: This device is completely internal, allowing for satisfactory joint
      motion during treatment in most patients. Lengthening was achieved in an
      accurate, controlled manner, and all patients reached their goal length.
      Complications remain a concern, as is the case with all approaches to this
      complex patient population. Both future comparative studies and longer-term
      followup are needed. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24664195
TI  - Is stability of the proximal tibiofibular joint important in the multiligament
      injured knee?
AB  - BACKGROUND: The incidence of proximal tibiofibular joint instability in the
      setting of the multiligament-injured knee has not been previously reported. The
      integrity of the proximal tibiofibular joint is required to perform a fibular
      based, lateral-sided knee reconstruction. QUESTIONS/PURPOSES: We report (1) the
      frequency of proximal tibiofibular joint instability in patients presenting with
      multiligament knee injuries and evaluate (2) our ability to restore stability to
      this joint, (3) patient-reported outcome scores, and (4) complications in
      patients surgically treated for proximal tibiofibular joint instability at the
      time of treatment of multiligament knee instability. METHODS: From 2005 to 2013,
      124 patients (129 knees) sustaining multiligament knee injuries with Grade 3
      instability to at least two ligaments were treated at our institution. We defined
      proximal tibiofibular joint instability as a dislocated or dislocatable proximal
      tibiofibular joint at the time of surgery. These patients underwent surgery to
      restore proximal tibiofibular joint stability and ligament reconstruction or
      repair and were followed with routine clinical examination, radiographs, and
      subjective outcome measures, including Lysholm and IKDC scores. Minimum followup
      was 12 months (mean, 32 months; range, 12-61 months). RESULTS: Twelve knees (12
      patients, 9% of 129 knees) showed proximal tibiofibular joint instability. Knee
      stability in 10 patients was restored to Grade 1 or less in all surgically
      treated ligaments. No proximal tibiofibular joint instability has recurred. No
      patients have complained of ankle stiffness or pain. In the ten patients with
      subjective scores, mean Lysholm score was 75 (range, 54-95) and mean IKDC score
      was 58 (range, 22-78). There were four complications: one failed posterolateral
      corner reconstruction, one proximal tibiofibular joint screw removal secondary to
      pain over the screw head, one deep infection treated with serial irrigation and
      debridements with graft retention, and one closed manipulation secondary to
      arthrofibrosis and loss of ROM. CONCLUSIONS: In the setting of multiligament
      injured knees, our series demonstrated a 9% incidence of proximal tibiofibular
      joint instability. The technique we describe successfully restored stability to
      the proximal tibiofibular joint and resulted in satisfactory patient-reported
      outcomes with low complication rates. LEVEL OF EVIDENCE: Level IV, therapeutic
      study. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24664196
TI  - Loosely implanted cementless stems may become rotationally stable after loading.
AB  - BACKGROUND: Experimental studies have suggested that initial micromotion of
      cementless components may lead to failure of osteointegration. Roentgen
      stereophotogrammetric analyses have shown durable implant fixation can be
      achieved long-term even when initial instability exists, as evidenced by
      subsidence. However improved implant stability as a result of subsidence, before
      osteointegration, has not been shown biomechanically. QUESTIONS/PURPOSES: We
      asked whether insertionally loose cementless tapered femoral stems show (1) less
      rotational stability (more toggle); (2) more subsidence; and (3) reduced ability
      to resist torsion (lower initial construct stiffness), lower torque at failure,
      and greater rotation to failure in comparison to well-fixed cementless tapered
      femoral stems. METHODS: Ten matched pairs of cadaveric femurs were implanted with
      well-fixed and loose cementless tapered stems. The loose stem construct was
      obtained by appropriately broaching the femur but afterwards inserting a stem one
      size smaller than that broached. Femoral stem rotational stability of implanted
      femurs was tested by measuring the angular rotation (ie, toggle) required to
      produce a torque of 2 N-m at 0 N, 250 N, and 500 N vertical load in 25 degrees 
      adduction simulating single-legged stance. Subsidence was measured as vertical
      movement during the toggle tests. Then at 500 N initial vertical load, femoral
      stems were externally rotated to failure. The construct stiffness between 5 and
      40 N-m was determined to assess ability to resist torsion. The torque and
      rotation to failure were recorded to compare failure characteristics. Groups were
      compared using mixed model ANOVA followed by Tukey-Kramer post hoc pairwise
      comparison for toggle and subsidence tests and by Student's paired t-tests for
      stiffness, torque at failure, and rotation to failure tests. RESULTS: Loose
      tapered cementless stems were less stable (ie, more toggle) than well-fixed at 0
      N of load (p < 0.0001), but no difference was detectable in toggle between loose
      and well-fixed stems at 250 N (p = 0.7019) and 500 N (p = 0.9970). Loose tapered
      cementless stems showed significant subsidence at 250 N (p < 0.0001) and 500 N (p
      < 0.0001), which was not found in the well-fixed stems at 250 N (p = 0.8813) and
      500 N (p = 0.1621). Torsional stiffness was lower for loose stems as compared
      with well-fixed stems (p = 0.0033). No difference in torque at failure (p =
      0.7568) or rotation to failure (p = 0.2629) was detected between loose and well
      fixed stems. CONCLUSIONS: In this study, we observed that insertionally loose
      cementless stems have the ability to subside and become rotationally stable with
      loading. They did not exhibit a lower torque or rotation to failure in comparison
      to well-fixed stems when under simulated single-legged stance. CLINICAL
      RELEVANCE: Secondary rotational stabilization may prevent insertionally loose
      tapered stems from producing a stress pattern that predisposes to early
      postoperative periprosthetic fracture around loose cemented stems.

PMID- 24664197
TI  - What are the advantages and disadvantages of imaging modalities to diagnose wear
      related corrosion problems?
AB  - BACKGROUND: Adverse tissue reactions are known to occur after total hip
      arthroplasty using both conventional and metal-on-metal (MoM) bearings and after
      MoM hip resurfacing arthroplasty (SRA). A variety of imaging tools, including
      ultrasound (US), CT, and MRI, have been used to diagnose problems associated with
      wear after MoM hip arthroplasty and corrosion at the head-trunnion junction;
      however, the relative advantages and disadvantages of each remain a source of
      controversy. QUESTIONS/PURPOSES: The purposes of this review were to evaluate the
      advantages and disadvantages of (1) US; (2) CT; and (3) MRI as diagnostic tools
      in the assessment of wear-related corrosion problems after hip arthroplasty.
      METHODS: A systematic literature review was performed through Medline, EMBASE,
      Scopus CINAHL, and the Cochrane Library without time restriction using search
      terms related to THA, SRA, US, CT, MRI, adverse tissue reactions, and corrosion.
      Inclusion criteria were Level I through IV studies in the English language,
      whereas expert opinions and case reports were excluded. The quality of included
      studies was judged by their level of evidence, method of intervention allocation,
      outcome assessments, and followup of patients. Four hundred ninety unique results
      were returned and 40 articles were reviewed. RESULTS: The prevalence of adverse
      local tissue reactions in both asymptomatic and symptomatic patients varies based
      on the method of evaluation (US, CT, MRI) and imaging protocols. US is accessible
      and relatively inexpensive, yet has not been used to report synovial thicknesses
      in the setting of wear-related corrosion. CT scans are highly sensitive and
      provide information regarding component positioning but are limited in providing
      enhanced soft tissue contrast and require ionizing radiation. MRI has shown
      promise in predicting both the presence and severity of adverse local tissue
      reactions but is more expensive. CONCLUSIONS: All three imaging modalities have a
      role in the assessment of adverse local tissue reactions and tribocorrosion after
      total hip arthroplasty. Although US may serve as a screening technique for the
      detection of larger periprosthetic collections, only MRI has been shown to
      predict the severity of tissue destruction found at revision and correlate to the
      degree of tissue necrosis at histologic evaluation.

PMID- 24664198
TI  - Effectiveness of sustained stretching of the inferior capsule in the management
      of a frozen shoulder.
AB  - BACKGROUND: Physiotherapy treatment of frozen shoulder is varied, but most lack
      specific focus on the underlying disorder, which is the adhered shoulder capsule.
      Although positive effects were found after physiotherapy, the recurrence and
      prolonged disability of a frozen shoulder are major factors to focus on to
      provide the appropriate treatment. QUESTIONS/PURPOSES: We wished to study the
      effectiveness of a shoulder countertraction apparatus on ROM, pain, and function
      in patients with a frozen shoulder and compare their results with those of
      control subjects who received conventional physiotherapy. METHODS: A total of 100
      participants were randomly assigned to an experimental group and a control group,
      with each group having 50 participants. The control group received physiotherapy
      and the experimental group received countertraction and physiotherapy. The total
      treatment time was 20 minutes a day for 5 days per week for 2 weeks. The outcome
      measures used were goniometer measurements, VAS, and the Oxford Shoulder Score.
      RESULTS: Improvements were seen in the scores for shoulder flexion (94.1 degrees 
      +/- 19.79 degrees  at baseline increased to 161.9 degrees  +/- 13.05 degrees 
      after intervention), abduction ROM (90.4 degrees  +/- 21.18 degrees  at baseline
      increased to 154.8 degrees  +/- 13.21 degrees  after intervention), and pain
      (8.00 +/- 0.78 at baseline decreased to 3.48 +/- 0.71 after intervention) in the
      experimental group. Sixty percent of the participants (n = 30) were improved to
      the fourth stage of satisfactory joint function according to the Oxford Shoulder
      Score in the experimental group compared with 18% (n = 9) in the control group (p
      < 0.001). CONCLUSIONS: Incorporating shoulder countertraction along with
      physiotherapy improves shoulder function compared with physiotherapy alone for
      the treatment of a frozen shoulder. Additional studies are needed focusing on
      this concept to increase the generalizability of the counter-traction apparatus
      in various groups. LEVEL OF EVIDENCE: Level II, prospective comparative study.
      See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24664199
TI  - Does intraarticular inflammation predict biomechanical cartilage properties?
AB  - BACKGROUND: Intact cartilage in the lateral compartment is an important
      requirement for medial unicompartmental knee arthroplasty (UKA). Progression of
      cartilage degeneration in the lateral compartment is a common failure mode of
      medial UKA. Little is known about factors that influence the mechanical
      properties of lateral compartment cartilage. QUESTIONS/PURPOSES: The purposes of
      this study were to answer the following questions: (1) Does the synovial fluid
      white blood cell count predict the biomechanical properties of macroscopically
      intact cartilage of the distal lateral femur? (2) Is there a correlation between
      MRI grading of synovitis and the biomechanical properties of macroscopically
      intact cartilage? (3) Is there a correlation between the histopathologic
      assessment of the synovium and the biomechanical properties of macroscopically
      intact cartilage? METHODS: The study included 84 patients (100 knees) undergoing
      primary TKA for varus osteoarthritis between May 2010 and January 2012. All
      patients underwent preoperative MRI to assess the degree of synovitis. During
      surgery, the cartilage of the distal lateral femur was assessed macroscopically
      using the Outerbridge grading scale. In knees with an Outerbridge grade of 0 or
      1, osteochondral plugs were harvested from the distal lateral femur for
      biomechanical and histologic assessment. The synovial fluid was collected to
      determine the white blood cell count. Synovial tissue was taken for histologic
      evaluation of the degree of synovitis. RESULTS: The mean aggregate modulus and
      the mean dynamic modulus were significantly greater in knees with 150 or less
      white blood cells/mL synovial fluid compared with knees with greater than 150
      white blood cells/mL synovial fluid. There was no correlation among MRI synovitis
      grades, histopathologic synovitis grades, and biomechanical cartilage properties.
      CONCLUSIONS: The study suggests that lateral compartment cartilage in patients
      with elevated synovial fluid white blood cell counts has a reduced ability to
      withstand compressive loads. LEVEL OF EVIDENCE: Level III, diagnostic study. See
      the Instructions for Authors for a complete description of levels of evidence.

PMID- 24664200
TI  - Enriched housing enhances recovery of limb placement ability and reduces aggrecan
      containing perineuronal nets in the rat somatosensory cortex after experimental
      stroke.
AB  - Stroke causes life long disabilities where few therapeutic options are available.
      Using electrical and magnetic stimulation of the brain and physical
      rehabilitation, recovery of brain function can be enhanced even late after
      stroke. Animal models support this notion, and housing rodents in an enriched
      environment (EE) several days after experimental stroke stimulates lost brain
      function by multisensory mechanisms. We studied the dynamics of functional
      recovery of rats with a lesion to the fore and hind limb motor areas induced by
      photothrombosis (PT), and with subsequent housing in either standard (STD) or EE.
      In this model, skilled motor function is not significantly enhanced by enriched
      housing, while the speed of recovery of sensori-motor function substantially
      improves over the 9-week study period. In particular, this stroke lesion
      completely obliterates the fore and hind limb placing ability when visual and
      whisker guidance is prevented, a deficit that persists for up to 9 weeks of
      recovery, but that is markedly restored within 2 weeks by enriched housing.
      Enriched housing after stroke also leads to a significant loss of perineuronal
      net (PNN) immunoreactivity; detection of aggrecan protein backbone with AB1031
      antibody was decreased by 13-22%, and labelling of a glycan moiety of aggrecan
      with Cat-315 antibody was reduced by 25-30% in the peri-infarct area and in the
      somatosensory cortex, respectively. The majority of these cells are
      parvalbumin/GABA inhibitory interneurons that are important in sensori
      information processing. We conclude that damage to the fore and hind limb motor
      areas provides a model of loss of limb placing response without visual guidance,
      a deficit also seen in more than 50% of stroke patients. This loss is amenable to
      recovery induced by multiple sensory stimulation and correlates with a decrease
      in aggrecan-containing PNNs around inhibitory interneurons. Modulating the PNN
      structure after ischemic damage may provide new therapies enhancing
      tactile/proprioceptive function after stroke. 

PMID- 24664201
TI  - Low bone density in achondroplasia.

PMID- 24664202
TI  - Abnormal functional brain connectivity and personality traits in myotonic
      dystrophy type 1.
AB  - IMPORTANCE: Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy
      observed in adults, is a genetic multisystem disorder affecting several other
      organs besides skeletal muscle, including the brain. Cognitive and personality
      abnormalities have been reported; however, no studies have investigated brain
      functional networks and their relationship with personality traits/disorders in
      patients with DM1. OBJECTIVE: To use resting-state functional magnetic resonance
      imaging to assess the potential relationship between personality traits/disorders
      and changes to functional connectivity within the default mode network (DMN) in
      patients with DM1. DESIGN, SETTING, AND PARTICIPANTS: We enrolled 27 patients
      with genetically confirmed DM1 and 16 matched healthy control individuals.
      Patients underwent personality assessment using clinical interview and Minnesota
      Multiphasic Personality Inventory-2 administration; all participants underwent
      resting-state functional magnetic resonance imaging. Investigations were
      conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia
      Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San
      Camillo Forlanini. INTERVENTION: Resting-state functional magnetic resonance
      imaging. MAIN OUTCOMES AND MEASURES: Measures of personality traits in patients
      and changes in functional connectivity within the DMN in patients and controls.
      Changes in functional connectivity and atypical personality traits in patients
      were correlated. RESULTS: We combined results obtained from the Minnesota
      Multiphasic Personality Inventory-2 and clinical interview to identify a
      continuum of atypical personality profiles ranging from schizotypal personality
      traits to paranoid personality disorder within our DM1 patients. We also
      demonstrated an increase in functional connectivity in the bilateral posterior
      cingulate and left parietal DMN nodes in DM1 patients compared with controls.
      Moreover, patients with DM1 showed strong associations between DMN functional
      connectivity and schizotypal-paranoid traits. CONCLUSIONS AND RELEVANCE: Our
      findings provide novel biological evidence that DM1 is a clinical condition that
      also involves an alteration of functional connectivity of the brain. We speculate
      that these functional brain abnormalities, similarly to frank psychiatric
      disorders, may account for the atypical personality traits observed in patients
      with DM1.

PMID- 24664203
TI  - The Arabidopsis protein CONSERVED ONLY IN THE GREEN LINEAGE160 promotes the
      assembly of the membranous part of the chloroplast ATP synthase.
AB  - The chloroplast F1Fo-ATP synthase/ATPase (cpATPase) couples ATP synthesis to the
      light-driven electrochemical proton gradient. The cpATPase is a multiprotein
      complex and consists of a membrane-spanning protein channel (comprising subunit
      types a, b, b', and c) and a peripheral domain (subunits alpha, beta, gamma,
      delta, and epsilon). We report the characterization of the Arabidopsis
      (Arabidopsis thaliana) CONSERVED ONLY IN THE GREEN LINEAGE160 (AtCGL160) protein
      (AtCGL160), conserved in green algae and plants. AtCGL160 is an integral
      thylakoid protein, and its carboxyl-terminal portion is distantly related to
      prokaryotic ATP SYNTHASE PROTEIN1 (Atp1/UncI) proteins that are thought to
      function in ATP synthase assembly. Plants without AtCGL160 display an increase in
      xanthophyll cycle activity and energy-dependent nonphotochemical quenching. These
      photosynthetic perturbations can be attributed to a severe reduction in cpATPase
      levels that result in increased acidification of the thylakoid lumen. AtCGL160 is
      not an integral cpATPase component but is specifically required for the efficient
      incorporation of the c-subunit into the cpATPase. AtCGL160, as well as a chimeric
      protein containing the amino-terminal part of AtCGL160 and Synechocystis sp.
      PCC6803 Atp1, physically interact with the c-subunit. We conclude that AtCGL160
      and Atp1 facilitate the assembly of the membranous part of the cpATPase in their
      hosts, but loss of their functions provokes a unique compensatory response in
      each organism. 

PMID- 24664204
TI  - Monoubiquitination of histone 2B at the disease resistance gene locus regulates
      its expression and impacts immune responses in Arabidopsis.
AB  - Disease resistance (R) genes are key components in plant immunity. Here, we show
      that Arabidopsis (Arabidopsis thaliana) E3 ubiquitin ligase genes HISTONE
      MONOUBIQUITINATION1 (HUB1) and HUB2 regulate the expression of R genes SUPPRESSOR
      OF npr1-1, CONSTITUTIVE1 (SNC1) and RESISTANCE TO PERONOSPORA PARASITICA4. An
      increase of SNC1 expression induces constitutive immune responses in the bonzai1
      (bon1) mutant, and the loss of HUB1 or HUB2 function reduces SNC1 up-regulation
      and suppresses the bon1 autoimmune phenotypes. HUB1 and HUB2 mediate histone 2B
      (H2B) monoubiquitination directly at the SNC1 R gene locus to regulate its
      expression. In addition, SNC1 and HUB1 transcripts are moderately up-regulated by
      pathogen infection, and H2B monoubiquitination at SNC1 is enhanced by pathogen
      infection. Together, this study indicates that H2B monoubiquitination at the R
      gene locus regulates its expression and that this histone modification at the R
      gene locus has an impact on immune responses in plants. 

PMID- 24664206
TI  - Truncation of LEAFY COTYLEDON1 protein is required for asexual reproduction in
      Kalanchoe daigremontiana.
AB  - Kalanchoe daigremontiana reproduces asexually by generating numerous plantlets on
      its leaf margins. The formation of plantlets requires the somatic initiation of
      organogenic and embryogenic developmental programs in the leaves. However, unlike
      normal embryogenesis in seeds, leaf somatic embryogenesis bypasses seed dormancy
      to form viable plantlets. In Arabidopsis (Arabidopsis thaliana), seed dormancy
      and embryogenesis are initiated by the transcription factor LEAFY COTYLEDON1
      (LEC1). The K. daigremontiana ortholog of LEC1 is expressed during leaf somatic
      embryo development. However, KdLEC1 encodes for a LEC1-type protein that has a
      unique B domain, with 11 unique amino acids and a premature stop codon. Moreover,
      the truncated KdLEC1 protein is not functional in Arabidopsis. Here, we show that
      K. daigremontiana transgenic plants expressing a functional, chimeric KdLEC1 gene
      under the control of Arabidopsis LEC1 promoter caused several developmental
      defects to leaf somatic embryos, including seed dormancy characteristics. The
      dormant plantlets also behaved as typical dormant seeds. Transgenic plantlets
      accumulated oil bodies and responded to the abscisic acid biosynthesis inhibitor
      fluridone, which broke somatic-embryo dormancy and promoted their normal
      development. Our results indicate that having a mutated form of LEC1 gene in K.
      daigremontiana is essential to bypass dormancy in the leaf embryos and generate
      viable plantlets, suggesting that the loss of a functional LEC1 promotes
      viviparous leaf somatic embryos and thus enhances vegetative propagation in K.
      daigremontiana. Mutations resulting in truncated LEC1 proteins may have been of a
      selective advantage in creating somatic propagules, because such mutations
      occurred independently in several Kalanchoe species, which form plantlets
      constitutively. 

PMID- 24664205
TI  - Accumulation of N-acetylglucosamine oligomers in the plant cell wall affects
      plant architecture in a dose-dependent and conditional manner.
AB  - To study the effect of short N-acetylglucosamine (GlcNAc) oligosaccharides on the
      physiology of plants, N-ACETYLGLUCOSAMINYLTRANSFERASE (NodC) of Azorhizobium
      caulinodans was expressed in Arabidopsis (Arabidopsis thaliana). The
      corresponding enzyme catalyzes the polymerization of GlcNAc and, accordingly,
      beta-1,4-GlcNAc oligomers accumulated in the plant. A phenotype characterized by
      difficulties in developing an inflorescence stem was visible when plants were
      grown for several weeks under short-day conditions before transfer to long-day
      conditions. In addition, a positive correlation between the oligomer
      concentration and the penetrance of the phenotype was demonstrated. Although NodC
      overexpression lines produced less cell wall compared with wild-type plants under
      nonpermissive conditions, no indications were found for changes in the amount of
      the major cell wall polymers. The effect on the cell wall was reflected at the
      transcriptome level. In addition to genes encoding cell wall-modifying enzymes, a
      whole set of genes encoding membrane-coupled receptor-like kinases were
      differentially expressed upon GlcNAc accumulation, many of which encoded proteins
      with an extracellular Domain of Unknown Function26. Although stress-related genes
      were also differentially expressed, the observed response differed from that of a
      classical chitin response. This is in line with the fact that the produced chitin
      oligomers were too small to activate the chitin receptor-mediated signal cascade.
      Based on our observations, we propose a model in which the oligosaccharides
      modify the architecture of the cell wall by acting as competitors in carbohydrate
      carbohydrate or carbohydrate-protein interactions, thereby affecting noncovalent
      interactions in the cell wall or at the interface between the cell wall and the
      plasma membrane. 

PMID- 24664207
TI  - The response of cyclic electron flow around photosystem I to changes in
      photorespiration and nitrate assimilation.
AB  - Photosynthesis captures light energy to produce ATP and NADPH. These molecules
      are consumed in the conversion of CO2 to sugar, photorespiration, and NO3(-)
      assimilation. The production and consumption of ATP and NADPH must be balanced to
      prevent photoinhibition or photodamage. This balancing may occur via cyclic
      electron flow around photosystem I (CEF), which increases ATP/NADPH production
      during photosynthetic electron transport; however, it is not clear under what
      conditions CEF changes with ATP/NADPH demand. Measurements of chlorophyll
      fluorescence and dark interval relaxation kinetics were used to determine the
      contribution of CEF in balancing ATP/NADPH in hydroponically grown Arabidopsis
      (Arabidopsis thaliana) supplied different forms of nitrogen (nitrate versus
      ammonium) under changes in atmospheric CO2 and oxygen. Measurements of CEF were
      made under low and high light and compared with ATP/NADPH demand estimated from
      CO2 gas exchange. Under low light, contributions of CEF did not shift despite an
      up to 17% change in modeled ATP/NADPH demand. Under high light, CEF increased
      under photorespiratory conditions (high oxygen and low CO2), consistent with a
      primary role in energy balancing. However, nitrogen form had little impact on
      rates of CEF under high or low light. We conclude that, according to modeled
      ATP/NADPH demand, CEF responded to energy demand under high light but not low
      light. These findings suggest that other mechanisms, such as the malate valve and
      the Mehler reaction, were able to maintain energy balance when electron flow was
      low but that CEF was required under higher flow. 

PMID- 24664208
TI  - Hybridization alters spontaneous mutation rates in a parent-of-origin-dependent
      fashion in Arabidopsis.
AB  - Over 70 years ago, increased spontaneous mutation rates were observed in
      Drosophila spp. hybrids, but the genetic basis of this phenomenon is not well
      understood. The model plant Arabidopsis (Arabidopsis thaliana) offers unique
      opportunities to study the types of mutations induced upon hybridization and the
      frequency of their occurrence. Understanding the mutational effects of
      hybridization is important, as many crop plants are grown as hybrids. Besides,
      hybridization is important for speciation and its effects on genome integrity
      could be critical, as chromosomal rearrangements can lead to reproductive
      isolation. We examined the rates of hybridization-induced point and frameshift
      mutations as well as homologous recombination events in intraspecific Arabidopsis
      hybrids using a set of transgenic mutation detector lines that carry mutated or
      truncated versions of a reporter gene. We found that hybridization alters the
      frequency of different kinds of mutations. In general, Columbia (Col)*Cape Verde
      Islands and Col*C24 hybrid progeny had decreased T->G and T->A transversion rates
      but an increased C->T transition rate. Significant changes in frameshift mutation
      rates were also observed in some hybrids. In Col*C24 hybrids, there is a trend
      for increased homologous recombination rates, except for the hybrids from one
      line, while in Col*Cape Verde Islands hybrids, this rate is decreased. The
      overall genetic distance of the parents had no influence on mutation rates in the
      progeny, as closely related accessions on occasion displayed higher mutation
      rates than accessions that are separated farther apart. However, reciprocal
      hybrids had significantly different mutation rates, suggesting parent-of-origin
      dependent effects on the mutation frequency.

PMID- 24664209
TI  - Mercury availability by operationally defined fractionation in granulometric
      distributions of soils and mine wastes from an abandoned cinnabar mine.
AB  - Mercury contamination from historic cinnabar mines represents a potential risk to
      the environment. Asturias, in Northern Spain, was one of the largest metallurgic
      and mining producer areas of Hg in Europe during the 20th century until the end
      of activities in 1974. Mining operations have caused Hg release and dispersion
      throughout the area. In this study, soils collected from calcine piles and
      surrounding soils at an abandoned Hg mine and metallurgical plant in Mieres
      (Asturias, Spain) were distributed in different particle-size subsamples.
      Fractionation of Hg was performed by means of a Hg-specific sequential extraction
      procedure complemented with the selective determination of organic Hg fraction by
      a specific extraction method. Extremely high concentrations of total Hg were
      found in calcine piles. Concentrations and mobility of Hg decreased markedly with
      the distance in soils located 25 m both above and below the chimney of the
      metallurgical plant. The sequential extraction results indicated that Hg is
      primarily found as elemental Hg followed by sulfide Hg in the finest subsamples.
      However, this distribution is inverted in the coarser grain fractions where
      sulfide Hg prevails. Calcine piles exhibited exceptionally high values of mobile
      Hg (up to 5350 MUg g(-1) in the finest subsample). Accumulation of Hg in the
      elemental Hg fraction was observed at decreasing grain size which is indicative
      of deposition of Hg vapors from the metallurgical plant. Enrichment of sulfide Hg
      was found in the finest subsamples of soils sampled below the chimney (up to 99
      MUg g(-1)). Significant organic Hg contents were observed in the soil samples (up
      to 2.8 MUg g(-1)), higher than those found in other abandoned Hg mining sites. A
      strong correlation was observed between organic Hg and Hg humic and fulvic
      complexes, as well as with the elemental Hg fraction. This indicates that both
      humic and fulvic material and elemental Hg must be the primary variables
      controlling Hg methylation in these soils.

PMID- 24664210
TI  - Off-label use of sodium valproate for schizophrenia.
AB  - BACKGROUND: Off-label use of a drug not according to its regulatory labeling has
      become common in medicine, especially in the field of psychiatry. Mood
      stabilizers are intended to be used to attenuate mood fluctuations in bipolar
      disorder, but their use has spread to patients with schizophrenia, as it provides
      greater control of impulsivity and aggressiveness. Sodium valproate is one of the
      most frequently used mood stabilizers in psychiatry. This study determined the
      prevalence of off-label use of sodium valproate for schizophrenia and
      schizoaffective disorder in Abarbanel Psychiatric Hospital and the demographic
      and clinical characteristics associated with its use. METHODS: Retrospective
      study of patients hospitalized in 2011-2012 with a diagnosis of schizophrenia or
      schizoaffective disorder in one of three general psychiatric wards. RESULTS:
      Valproate use was significantly lower in the geriatric group (11.6% vs. 20.1%,
      chi square  = 4.7, p = .03), in patients with schizophrenia (14.1% vs.
      schizoaffective disorder (35.2%), chi square  = 29, p<.001) and in patients
      receiving both atypical and typical antipsychotics (23.3% vs. 16.4%, p = .04). In
      multivariate logistic regression analysis, diagnosis and the combination of
      atypical and typical antipsychotics predicted the use of sodium valproate. The
      number of other medications prescribed did not predict sodium valproate use.
      CONCLUSIONS: Off-label use of sodium valproate in psychiatric patients with
      schizophrenia or schizoaffective disorder is extensive, especially in younger
      patients and those with schizoaffective disorder. More research is needed to
      determine whether it is being prescribed appropriately.

PMID- 24664211
TI  - Mechanodelivery of nanoparticles to the cytoplasm of living cells.
AB  - Nanotechnology has opened up the opportunity to probe, sense, and manipulate the
      chemical environment of biological systems with an unprecedented level of
      spatiotemporal control. A major obstacle to the full realization of these novel
      technologies is the lack of a general, robust, and simple method for the delivery
      of arbitrary nanostructures to the cytoplasm of intact live cells. Here, we
      identify a new delivery modality, based on mechanical disruption of the plasma
      membrane, which efficiently mediates the delivery of nanoparticles to the
      cytoplasm of mammalian cells. We use two distinct execution modes, two adherent
      cell lines, and three sizes of semiconducting nanocrystals, or quantum dots, to
      demonstrate its applicability and effectiveness. As the underlying mechanism is
      purely physical, we anticipate that such "mechanodelivery" can be generalized to
      other modes of execution as well as to the cytoplasmic introduction of a
      structurally diverse array of functional nanomaterials. 

PMID- 24664212
TI  - Bentuhua: culturing psychotherapy in postsocialist China.
AB  - The breathless pace of market reform in China has brought about profound ruptures
      in socioeconomic structures and increased mental distress in the population. In
      this context, more middle-class urbanites are turning to nascent psychological
      counseling to grapple with their problems. This article examines how Chinese
      psychotherapists attempt to "culture" or indigenize (bentuhua) three imported
      psychotherapy models in order to fit their clients' expectations, desires, and
      sensibilities: the Satir family therapy, cognitive behavioral therapy, and
      sandplay therapy. It addresses three interrelated questions: What is the role of
      culture in adopting, translating, and recasting psychotherapy in contemporary
      China? How is cultural difference understood and mobilized by therapists in the
      therapeutic encounter? What kind of distinct therapeutic relationship is emerging
      in postsocialist China? Data presented here are drawn from my semistructured
      interviews and extensive participant observation at various counseling offices
      and psychotherapy workshops in the city of Kunming. My ethnographic account
      suggests that it is through constant dialog, translation, and re-articulation
      between multiple regimes of knowledge, cultural values, and social practices that
      a new form of talk therapy with "Chinese characteristics" is emerging. Finally, I
      reflect upon what this dialogic process of transformation means for psychotherapy
      as a form of globally circulating knowledge/practice. 

PMID- 24664213
TI  - Expression of the sFLT1 gene in cord blood cells is associated to maternal
      arsenic exposure and decreased birth weight.
AB  - There is increasing epidemiologic evidence that arsenic exposure in utero is
      associated with adverse pregnancy outcomes and may contribute to long-term health
      effects. These effects may occur at low environmental exposures but the
      underlying molecular mechanism is not clear. We collected cord blood samples of
      183 newborns to identify associations between arsenic levels and birth
      anthropometric parameters in an area with very low arsenic exposure. Our core
      research aim was to screen for transcriptional marks that mechanistically explain
      these associations. Multiple regression analyses showed that birth weight
      decreased with 47 g (95% CI: 16-78 g) for an interquartile range increase of 0.99
      MUg/L arsenic. The model was adjusted for child's sex, maternal smoking during
      pregnancy, gestational age, and parity. Higher arsenic concentrations and reduced
      birth weight were positively associated with changes in expression of the sFLT1
      (soluble fms-like tyrosine kinase-1) gene in cord blood cells in girls. The
      protein product of sFLT1 is a scavenger of vascular endothelial growth factor
      (VEGF) in the extracellular environment and plays a key role in the inhibition of
      placental angiogenesis. In terms of fetal development, inhibition of placental
      angiogenesis leads to impaired nutrition and hence to growth retardation. Various
      genes related to DNA methylation and oxidative stress showed also changed
      expression in relation to arsenic exposure but were not related to birth outcome
      parameters. In conclusion, this study suggests that increased expression of sFLT1
      is an intermediate marker that points to placental angiogenesis as a pathway
      linking prenatal arsenic exposure to reduced birth weight. 

PMID- 24664214
TI  - Where, when and what? A time study of surgeons' work in urology.
AB  - INTRODUCTION: Staff time is a relevant resource in the delivery of health care
      interventions. Its measurement is a prerequisite for unit costing but usually
      complex. The aim of this study was to analyse the distribution of surgeons' work
      time among types and places of activities. A second aim was to use these data to
      calculate costs per unit of output. METHODS: A self-reporting work sampling study
      was carried out at a department of Urology. All of twelve surgeons involved in
      clinical care participated in a two-week analysis of their work time. RESULTS: A
      total of 2,485 data-points were collected, representing about 1,242 hours of work
      time. Surgeons spent the greater part of their work time in direct patient care,
      but substantial shares were required for documentation and organisation.
      Assistants were mainly required at the wards and consultants at the operating
      theatre and the outpatient unit. Staff costs of surgeons were 32 ? and 29 ? per
      patient day at the wards, respectively, 1.30 ? per minute at the operating
      theatre and 32 ? per visit at the outpatient unit. CONCLUSION: Results provided a
      basis for costing of health care interventions at the study site. However, future
      research should focus on the establishment of standardised terminology in order
      to increase transferability of results.

PMID- 24664215
TI  - Improving the clinical prediction of detrusor overactivity by utilizing
      additional symptoms and signs to overactive bladder symptoms alone.
AB  - INTRODUCTION AND HYPOTHESIS: We attempted to improve the accuracy of the clinical
      diagnosis of detrusor overactivity (DO) by using other significant clinical
      parameters in addition to overactive bladder (OAB) symptoms alone. METHODS: One
      thousand one hundred and forty women attending for their initial urogynecological
      assessment, including urodynamics, due to symptoms of pelvic floor dysfunction,
      underwent a comprehensive clinical and urodynamic assessment. Multivariate
      logistic regression analysis of a wide range of clinical parameters was used in
      order to determine a model of factors most accurately predicting the urodynamic
      diagnosis of DO. Data were separated according to women without DO; women with
      DO. The analysis involved the stepwise building of an optimal clinical model for
      predicting DO. RESULTS: In multivariate analysis, the OAB symptoms of urgency
      incontinence, urgency and nocturia (not frequency) were significantly associated
      with DO. Their prediction of DO was not particularly accurate (sensitivity 0.64;
      specificity 0.67). The addition of other significant clinical parameter, i.e.
      absent symptoms of stress incontinence; lower parity (0-1); no signs of prolapse,
      to the diagnostic model, resulted in marginally improved accuracy (area under the
      ROC curve increased from 0.70 to 0.74). CONCLUSIONS: Overactive bladder symptoms
      alone are not accurate in predicting DO. Adding other significant clinical
      parameters to the model resulted in a small statistical advantage, which is not
      clinically useful. An accurate clinical diagnosis of DO in women would appear to
      remain elusive.

PMID- 24664216
TI  - Immune dysregulation and endothelial dysfunction in pulmonary arterial
      hypertension: a complex interplay.

PMID- 24664217
TI  - Coronary artery computed tomography scanning.

PMID- 24664218
TI  - ECG response: March 25, 2014.

PMID- 24664219
TI  - Catecholamine-induced myocarditis in pheochromocytoma.

PMID- 24664220
TI  - A word of caution: risk of device erosion after percutaneous treatment of atrial
      septal defect in patients with dilated aortic root.

PMID- 24664221
TI  - Select articles published on the topic of cardiovascular surgery in 2013.

PMID- 24664222
TI  - Letter by Stocker and Maghzal regarding article, "Mitochondrial DNA damage can
      promote atherosclerosis independently of reactive oxygen species through effects
      on smooth muscle cells and monocytes and correlates with higher-risk plaques in
      humans".

PMID- 24664223
TI  - Response to letter regarding article, "Mitochondrial DNA damage can promote
      atherosclerosis independently of reactive oxygen species through effects on
      smooth muscle cells and monocytes and correlates with higher-risk plaques in
      humans".

PMID- 24664225
TI  - The highly enhanced performance of lamellar WS2 nanosheet electrodes upon
      intercalation of single-walled carbon nanotubes for supercapacitors and lithium
      ions batteries.
AB  - Hybrid lamellar porous electrodes with excellent electrochemical performance were
      successfully fabricated by homogeneously intercalating single-walled carbon
      nanotubes into the lamellar assembled WS2 nanosheets through vacuum filtration. 

PMID- 24664224
TI  - Association of DSC3 mRNA down-regulation in prostate cancer with promoter
      hypermethylation and poor prognosis.
AB  - BACKGROUND: Desmocollin 3 (DSC3), a member of the cadherin gene superfamily, is
      associated with pathogenesis of some cancers, but its role in prostate cancer
      (PCa) remains largely unknown. METHODS: DSC3 gene expression level in available
      PCa microarray dataset was examined using the Oncomine database. DSC3 transcript
      expression in prostate cell line panel and an independent tissue cohort (n = 52)
      was estimated by quantitative PCR (Q-PCR). Epigenetic status of DSC3 gene
      promoter in PCa was investigated by uploading three dataset (ENCODE Infinium 450K
      array data and two methylation sequencing) in UCSC genome browser. While
      pyrosequencing analysis measured promoter DNA methylation, Q-PCR estimates were
      obtained for DSC3 transcript re-expression after 5-Aza-deoxycytidine (5-Aza)
      treatment. Clinical relevance of DSC3 expression was studied by Kaplan-Meier
      survival analysis. Finally, functional studies monitoring cell proliferation,
      migration and invasion were performed in prostate cell lines after siRNA mediated
      DSC3 knockdown or following 5-Aza induced re-expression. EMT markers Vimentin and
      E-cadherin expression was measured by Western Blot. RESULTS: Microarray data
      analyses revealed a significant decrease in DSC3 transcript expression in PCa,
      compared to benign samples. Q-PCR analysis of an independent cohort revealed DSC3
      transcript down-regulation, both in PCa cell lines and tumor tissues but not in
      their benign counterpart. Examination of available NGS and Infinium data
      identified a role for epigenetic regulation DSC3 mRNA reduction in PCa.
      Pyrosequencing confirmed the increased DSC3 promoter methylation in cancer cell
      lines and restoration of transcript expression upon 5-Aza treatment further
      corroborated this epigenetic silencing mechanism. Importantly Kaplan-Meier
      analysis of an outcome cohort showed an association between loss of DSC3
      expression and significantly increased risk of biochemical recurrence. Functional
      studies indicate a role for epithelial-mesenchymal transition in DSC3 regulated
      cell migration/invasion. CONCLUSION: Taken together, our data suggests that DNA
      methylation contributes to down-regulation of DSC3 in prostate cancer, and loss
      of DSC3 predicts poor clinical outcome.

PMID- 24664226
TI  - Impact of hexavalent chromium on mammalian cell bioenergetics: phenotypic
      changes, molecular basis and potential relevance to chromate-induced lung cancer.
AB  - Occupational exposure to hexavalent chromium [Cr(VI)] has been firmly associated
      with the development of several pathologies, notably lung cancer. According to
      the current paradigm, the evolution of normal cells to a neoplastic state is
      accompanied by extensive metabolic reprogramming, namely at the level of energy
      transducing processes. Thus, a complete understanding of the molecular basis of
      Cr(VI)-induced lung cancer must encompass the elucidation of the impact of Cr(VI)
      on metabolism. Research in this area is still in its infancy. Nonetheless, Cr(VI)
      induced metabolic phenotypes are beginning to emerge. Specifically, it is now
      well documented that Cr(VI) exposure inhibits respiration and negatively affects
      the cellular energy status. Furthermore, preliminary results suggest that it also
      upregulates glucose uptake and lactic acid fermentation. From a mechanistic point
      of view, there is evidence that Cr(VI) exposure can interfere with energy
      transducing pathways at different levels, namely gene expression, intracellular
      protein levels and/or protein function. Loss of thiol redox control likely plays
      a key role in these processes. The transcriptional networks that control energy
      transduction can likewise be affected. Data also suggest that Cr(VI) exposure
      might compromise energy transducing processes through changes in the
      intracellular pools of their substrates. This article reviews, for the first
      time, the information available on Cr(VI) impact on mammalian cell bioenergetics.
      It aims to provide a framework for the understanding of the role played by
      bioenergetics in Cr(VI)-induced carcinogenesis and is also intended as a guide
      for future research efforts in this area. 

PMID- 24664228
TI  - Ilizarov external fixation or locked intramedullary nailing in diaphyseal tibial
      fractures: a randomized, prospective study of 58 consecutive patients.
AB  - PURPOSE: The aim of this study was to compare the Ilizarov circular fixator (IL)
      and locked intramedullary nailing (IM). PATIENTS AND METHODS: Patients with
      isolated tibia shaft fractures were randomly allocated to either the IL (n = 31)
      or IM (n = 27) method. Conventional radiographs, postoperative pain assessment,
      self-appraisal scores and complications were evaluated. At the clinical 1-year
      follow-up, the patients were also evaluated by an independent observer. RESULTS:
      The minority of patients had open fractures, two and nine patients in the IM and
      IL groups, respectively. Eight patients in the IM group and four in the IL group
      sustained major complications (p = 0.107). In the IM group, two patients
      developed compartment syndrome, one deep infection, one hardware failure, one
      delayed union, one pseudarthrosis and two had a malunion. In the IL group, two
      patients developed pseudarthrosis and two had a malunion. Superficial pin-site
      infections were observed in 16 patients in the IL group. The fractures had healed
      radiographically at 12 weeks in both groups. At the 1-year follow-up, there were
      differences in pain (VAS) and satisfaction (VAS) scores in favor of IL treatment
      (VAS, p = 0.03 and p = 0.02, respectively). There were no differences between the
      groups with regard to range of motion (ROM) in the knee and ankle joints. The
      registration of local tenderness and pain revealed that there were 19 patients
      with anterior knee pain in the IM group and one in the IL group at the 1-year
      follow-up (p < 0.001). CONCLUSION: The IL is a safe and reliable alternative to
      IM for the treatment of tibial shaft fractures, with a low complication rate and
      good clinical outcome. Both treatments were well tolerated, but at the 1-year
      follow-up the patients in the IM group had more pain and were less satisfied.
      Finally, there was a high frequency of anterior knee pain in the IM group.

PMID- 24664230
TI  - How to improve access to appropriate therapy and outcome of the acute ischemic
      stroke: a 24-month survey of a specific pre-hospital planning in Northern Italy.
AB  - Few patients with acute cerebral infarction are medicated with thrombolysis as
      yet. Thus, a specific plan was created in the area of Bergamo in Northern Italy
      to increase the number of procedures. The plan, started in 2010, consisted of:
      (1) subdivision of the area of Bergamo into three zones, each one served by a
      single Stroke-Unit (SU) licensed to thrombolysis; (2) information to population
      via newspapers and local broadcasting; and (3) teachings both to personnel of
      Emergency Medical Service and General Practitioners. Here, we have compared the
      results of the SU of Policlinico San Marco in the years 2008-2009 versus those in
      the years 2010-2011. During 2008 and 2009, SU admitted 376 acute ischemic
      strokes, 60 of whom (16 %) within 3 h of the event. Of those patients, 8 (2 %)
      were treated with thrombolysis. At 3 months of stroke, 61 patients (16 %) were
      alive and self-independent. During 2010 and 2011, SU admitted 401 acute ischemic
      strokes, 91 of whom (22 %) within 3 h of stroke. Of those patients, 23 (6 %) were
      treated with thrombolysis. At 3 months of stroke, 100 patients were alive and
      self-independent (25 %). The increases of thrombolytic procedures (p = 0.0171),
      of self-independent patients (p = 0.0036), and of patients arriving within 3 h of
      stroke (p = 0.0226) were statistically significant. In conclusion, our study
      shows that a specific plan increases the numbers of thrombolysis and of self
      independent patients at 3 months of stroke.

PMID- 24664231
TI  - Delusional jealousy in Parkinson's disease patients with and without dementia.

PMID- 24664232
TI  - Cloning, overexpression, and characterization of a high enantioselective
      nitrilase from Sphingomonas wittichii RW1 for asymmetric synthesis of (R)
      phenylglycine.
AB  - In this study, a high (R)-enantioselective nitrilase gene from Sphingomonas
      wittichii RW1 was cloned and overexpressed in Escherichia coli BL21 (DE3). The
      recombinant nitrilase was purified to homogeneity with a molecular weight of 40
      kDa. The pH and temperature optima were shown to be pH 8.0 and 40  degrees C,
      respectively. The purified nitrilase was most active toward succinonitrile,
      approximately 30-fold higher than that for phenylglycinonitrile. Using the E.
      coli BL21/ReSWRW1 whole cells as biocatalysts, the kinetic resolution for
      asymmetric synthesis of (R)-phenylglycine was investigated at pH 6.0. A yield of
      46 % was obtained with 95 % enantiomeric excess (ee), which made it a promising
      biocatalyst for synthesis of (R)-phenylglycine.

PMID- 24664233
TI  - Expression and purification of bioactive high-purity recombinant mouse SPP1 in
      Escherichia coli.
AB  - Secreted phosphoprotein 1 (SPP1) is a phosphorylated acidic glycoprotein. It is
      broadly expressed in a variety of tissues, and it is involved in a number of
      physiological and pathological events, including cancer metastasis, tissues
      remodeling, pro-inflammation regulation, and cell survival. SPP1 has shown its
      function of protecting tissues and organs against injury and wound, giving itself
      potentials to become a therapy target or giving its antibodies of other counter
      acting reagents potentials to become drug candidates. Non-tagged (native)
      recombinant SPP1 would be valuable in therapeutic and pharmaceutical researches.
      In our study, mouse Spp1 DNA fragment without signal peptide was built in
      pET28a(+) vector and transformed into Escherichia coli BL21 (DE3). The
      recombinant mouse SPP1 (rmSPP1) was then expressed in bacteria upon induction by
      isopropyl beta-D-thiogalactopyranoside (IPTG). The abundance of rmSPP1 was
      increased using isoelectric precipitation and ammonium sulfate fractionation
      methods, and anion and cation exchange chromatography was employed to further
      purify rmSPP1. Finally, we got rmSPP1 product with 12.8 % productivity, 97 %
      purity, satisfactory bioactivity, and low endotoxin content.

PMID- 24664234
TI  - Identification, cloning and biochemical characterization of Pseudomonas putida A
      (ATCC 12633) monooxygenase enzyme necessary for the metabolism of
      tetradecyltrimethylammonium bromide.
AB  - This study presents the first report of the purification and characterization of
      a monooxygenase enzyme from Pseudomonas putida A (ATCC 12633) that is responsible
      for the oxidation of physiologically relevant quaternary ammonium compounds, the
      tetradecyltrimethylammonium bromide. The degradation of
      tetradecyltrimethylammonium bromide by P. putida A (ATCC 12633) is initiated by N
      dealkylation and catalysed by tetradecyltrimethylammonium monooxygenase (TTABMO),
      resulting in the formation of tetradecylalkanal and trimethylamine. Based on
      sequence analysis, the gene for TTABMO (ttbmo) corresponded to an ORF named
      PP2033 in the genome of P. putida KT2440. Mutation in ttabmo blocked the
      utilization of tetradecyltrimethylammonium bromide by Pseudomonas putida A (ATCC
      12633) as carbon and nitrogen sources. The enzyme can be highly overexpressed in
      P. putida Deltattabmo-T7 in active form and purified as a hexahistidine fusion
      protein. Like the native enzyme, the his-TTABMO was found to be a monomer with
      molecular mass of 40 kDa, the isoelectric point 7.3, that catalyses the breakdown
      of tetradecyltrimethylammonium bromide and utilized NADPH and FAD as cofactor.
      The biochemical properties and the analysis of the respective protein sequence
      revealed that TTABMO represents a typical flavoprotein monooxygenase, which is
      member of a flavoprotein family that is distinct from Baeyer-Villiger
      monooxygenases.

PMID- 24664235
TI  - Design of multicomponent photocatalysts for hydrogen production under visible
      light using water-soluble titanate nanodisks.
AB  - We report the design of efficient multicomponent photocatalysts (MPs) for H2
      production under visible light by using water-soluble ultrathin titanate
      nanodisks (TNDs) stabilized by tetraethylammonium cations (TEA(+)) as building
      blocks. The photocatalysts are designed in such a way to significantly enhance
      simultaneously the efficiency of the three main steps in the photocatalytic
      process i.e., light absorption, charge separation and catalytic reaction. We
      show, as an example, the construction of water-soluble CdS-TND-Ni MPs. The
      designed CdS-TND-Ni MPs, in which CdS nanoparticles and TNDs are intimately
      assembled to enhance the charge transfer and surface area, are controlled in
      composition to optimize visible light absorption. The conception of the MPs
      allows them to be highly dispersed in water which markedly improves the
      photocatalytic H2 production process. Most importantly, a Ni co-catalyst is
      selectively located on the surface of TNDs, enabling vectorial electron transfer
      from CdS to TND and to Ni, which drastically improves the charge separation.
      Consequently, under visible light illumination (lambda >= 420 nm), the optimally
      designed CdS-TND-Ni MPs could generate H2 from ethanol-water solution with rate
      as high as 15.326 mmol g(-1) h(-1) during a reaction course of 15 h and with an
      apparent quantum yield of 24% at 420 nm. Moreover, we also demonstrate that TNDs
      can be combined with other single or mixed metal sulfide to form water-soluble
      metal sulfide-TNDs composites which could also be of great interest for
      photocatalytic H2 production. 

PMID- 24664236
TI  - Isotopes and trace elements as natal origin markers of Helicoverpa armigera--an
      experimental model for biosecurity pests.
AB  - Protecting a nation's primary production sector and natural estate is heavily
      dependent on the ability to determine the risk presented by incursions of exotic
      insect species. Identifying the geographic origin of such biosecurity breaches
      can be crucial in determining this risk and directing the appropriate operational
      responses and eradication campaigns, as well as ascertaining incursion pathways.
      Reading natural abundance biogeochemical markers using mass spectrometry is a
      powerful tool for tracing ecological pathways as well as provenance determination
      of commercial products and items of forensic interest. However, application of
      these methods to trace insects has been underutilised to date and our
      understanding in this field is still in a phase of basic development. In
      addition, biogeochemical markers have never been considered in the atypical
      situation of a biosecurity incursion, where sample sizes are often small, and of
      unknown geographic origin and plant host. These constraints effectively confound
      the interpretation of the one or two isotope geo-location markers systems that
      are currently used, which are therefore unlikely to achieve the level of
      provenance resolution required in biosecurity interceptions. Here, a novel
      approach is taken to evaluate the potential for provenance resolution of insect
      samples through multiple biogeochemical markers. The international pest,
      Helicoverpa armigera, has been used as a model species to assess the validity of
      using naturally occurring delta2H, 87Sr/86Sr, 207Pb/206Pb and 208Pb/206Pb isotope
      ratios and trace element concentration signatures from single moth specimens for
      regional assignment to natal origin. None of the biogeochemical markers selected
      were individually able to separate moths from the different experimental regions
      (150-3000 km apart). Conversely, using multivariate analysis, the region of
      origin was correctly identified for approximately 75% of individual H. armigera
      samples. The geographic resolution demonstrated with this approach has
      considerable potential for biosecurity as well as other disciplines including
      forensics, ecology and pest management. 

PMID- 24664237
TI  - The alpha7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial
      clearance in mice by restoring hyperoxia-compromised macrophage function.
AB  - Mechanical ventilation with supraphysiological concentrations of oxygen
      (hyperoxia) is routinely used to treat patients with respiratory distress.
      However, prolonged exposure to hyperoxia compromises the ability of the
      macrophage to phagocytose and clear bacteria. Previously, we showed that the
      exposure of mice to hyperoxia elicits the release of the nuclear protein high
      mobility group box-1 (HMGB1) into the airways. Extracellular HMGB1 impairs
      macrophage phagocytosis and increases the mortality of mice infected with
      Pseudomonas aeruginosa (PA). The aim of this study was to determine whether GTS
      21 [3-(2,4 dimethoxybenzylidene)-anabaseine dihydrochloride], an alpha7 nicotinic
      acetylcholine receptor (alpha7nAChR) agonist, could inhibit hyperoxia-induced
      HMGB1 release into the airways, enhance macrophage function and improve bacterial
      clearance from the lungs in a mouse model of ventilator-associated pneumonia. GTS
      21 (0.04, 0.4 and 4 mg/kg) or saline was systemically administered via
      intraperitoneal injection to mice that were exposed to hyperoxia (>=99% O2) and
      subsequently challenged with PA. We found that systemic administration of 4 mg/kg
      GTS-21 significantly increased bacterial clearance, decreased acute lung injury
      and decreased accumulation of airway HMGB1. To investigate the cellular mechanism
      of these observations, RAW 264.7 cells, a macrophagelike cell line, were
      incubated with different concentrations of GTS-21 in the presence of 95% O2. The
      phagocytic activity of macrophages was significantly increased by GTS-21 in a
      dose-dependent manner. In addition, hyperoxia-induced hyperacetylation of HMGB1
      was significantly reduced in macrophages incubated with GTS-21. Furthermore, GTS
      21 significantly inhibited the cytoplasmic translocation and release of HMGB1
      from these macrophages. Our results indicate that GTS-21 is effective in
      improving bacterial clearance and reducing acute lung injury by enhancing
      macrophage function via inhibiting the release of nuclear HMGB1. Therefore, the
      alpha7nAChR represents a possible pharmacological target to improve the clinical
      outcome of patients on ventilators by augmenting host defense against bacterial
      infections. 

PMID- 24664238
TI  - CCHCR1 interacts specifically with the E2 protein of human papillomavirus type 16
      on a surface overlapping BRD4 binding.
AB  - The Human Papillomavirus E2 proteins are key regulators of the viral life cycle,
      whose functions are commonly mediated through protein-protein interactions with
      the host cell proteome. We identified an interaction between E2 and a cellular
      protein called CCHCR1, which proved highly specific for the HPV16 genotype, the
      most prevalent in HPV-associated cancers. Further characterization of the
      interaction revealed that CCHCR1 binds the N-terminal alpha helices of HPV16 E2 N
      terminal domain. On this domain, the CCHCR1 binding interface overlaps that of
      BRD4, a key mediator of E2 transcriptional activity. Consequently a physical
      competition occurs between the two proteins for the binding to HPV16 E2, and
      CCHCR1 interferes with BRD4-mediated enhancement of E2-dependent transcription.
      In addition, we showed that the interaction with CCHCR1 induced a massive
      redistribution of HPV16 E2, from a predominantly nuclear to a cytoplasmic
      localization in dot-like structures, where E2 perfectly co-localizes with CCHCR1.
      Such a cytoplasmic docking likely interferes with the nuclear functions of HPV16
      E2. Upon co-expression of BRD4 and CCHCR1, E2 accumulates both in the nucleus and
      in the cytoplasm, indicating that for HPV16, both sub-cellular localization and
      transcriptional functions of E2 may depend on the proportion of both factors
      within the cell. We provided evidence of a strong induction of the keratinocyte
      differentiation marker K10 by HPV16 E2, and showed that this activation is
      compromised by the interaction with CCHCR1. The specific interaction described
      here could thus impact on the pathogenesis of HPV16. We propose that it could
      underlie some specific traits of HPV16 infection, such as an enhanced propensity
      to give rise to lesions evolving toward cancer. 

PMID- 24664239
TI  - The harm argument against surrogacy revisited: two versions not to forget.
AB  - It has been a common claim that surrogacy is morally problematic since it
      involves harm to the child or the surrogate-the harm argument. Due to a growing
      body of empirical research, the harm argument has seen a decrease in popularity,
      as there seems to be little evidence of harmful consequences of surrogacy. In
      this article, two revised versions of the harm argument are developed. It is
      argued that the two suggested versions of the harm argument survive the current
      criticism against the standard harm argument. The first version argues that the
      child is harmed by being separated from the gestational mother. The second
      version directs attention to the fact that surrogacy involves great incentives to
      keep the gestational mother's level of maternal-fetal attachment low, which tend
      to increase the risk of harm to the child. While neither of the two arguments is
      conclusive regarding the moral status of surrogacy, both constitute important
      considerations that are often ignored. 

PMID- 24664241
TI  - Evolving shale gas management: water resource risks, impacts, and lessons
      learned.
AB  - Unconventional shale gas development promises to significantly alter energy
      portfolios and economies around the world. It also poses a variety of
      environmental risks, particularly with respect to the management of water
      resources. We review current scientific understanding of risks associated with
      the following: water withdrawals for hydraulic fracturing; wastewater treatment,
      discharge and disposal; methane and fluid migration in the subsurface; and spills
      and erosion at the surface. Some of these risks are relatively unique to shale
      gas development, while others are variations of risks that we already face from a
      variety of industries and activities. All of these risks depend largely on the
      pace and scale of development that occurs within a particular region. We focus on
      the United States, where the shale gas boom has been on-going for several years,
      paying particular attention to the Marcellus Shale, where a majority of peer
      reviewed study has taken place. Governments, regulatory agencies, industry, and
      other stakeholders are challenged with responding to these risks, and we discuss
      policies and practices that have been adopted or considered by these various
      groups. Adaptive Management, a structured framework for addressing complex
      environmental issues, is discussed as a way to reduce polarization of important
      discussions on risk, and to more formally engage science in policy-making, along
      with other economic, social and value considerations. Data suggests that some
      risks can be substantially reduced through policy and best practice, but also
      that significant uncertainty persists regarding other risks. We suggest that
      monitoring and data collection related to water resource risks be established as
      part of planning for shale gas development before activity begins, and that
      resources are allocated to provide for appropriate oversight at various levels of
      governance. 

PMID- 24664240
TI  - The Association between active and passive smoking and latent tuberculosis
      infection in adults and children in the united states: results from NHANES.
AB  - BACKGROUND: Few studies assessing the relationship between active and passive
      smoking and tuberculosis have used biomarkers to measure smoke exposure. We
      sought to determine the association between active and passive smoking and LTBI
      in a representative sample of US adults and children. METHODS: We used the 1999
      2000 US National Health and Nutrition Examination Survey (NHANES) dataset with
      tuberculin skin test (TST) data to assess the association between cotinine
      confirmed smoke exposure and latent tuberculosis infection (LTBI) among adults
      ages >=20 years (n = 3598) and children 3-19 years (n = 2943) and estimate the
      prevalence of smoke exposure among those with LTBI. Weighted multivariate
      logistic regression was used to measure the associations between active and
      passive smoking and LTBI. RESULTS: LTBI prevalence in 1999-2000 among cotinine
      confirmed active, passive, and non-smoking adults and children was 6.0%, 5.2%,
      3.3% and 0.3%, 1.0%, 1.5%, respectively. This corresponds to approximately
      3,556,000 active and 3,379,000 passive smoking adults with LTBI in the US
      civilian non-institutionalized population in 1999-2000. Controlling for age,
      gender, socioeconomic status, race, birthplace (US vs. foreign-born), household
      size, and having ever lived with someone with TB, adult active smokers were
      significantly more likely to have LTBI than non-smoking adults (AOR = 2.31 95% CI
      1.17-4.55). Adult passive smokers also had a greater odds of LTBI compared with
      non-smokers, but this association did not achieve statistical significance (AOR =
      2.00 95% CI 0.87-4.60). Neither active or passive smoking was associated with
      LTBI among children. Among only the foreign-born adults, both active (AOR = 2.56
      (95% CI 1.20-5.45) and passive smoking (AOR = 2.27 95% CI 1.09-4.72) were
      significantly associated with LTBI. CONCLUSIONS: Active adult smokers and both
      foreign-born active and passive smokers in the United States are at elevated risk
      for LTBI. Targeted smoking prevention and cessation programs should be included
      in comprehensive national and international TB control efforts.

PMID- 24664227
TI  - A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson
      disease: no evidence of benefit.
AB  - IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial
      function, has been shown in preclinical Parkinson disease (PD) models to reduce
      the loss of dopamine neurons, and was safe and well tolerated in early-phase
      human studies. A previous phase II study suggested possible clinical benefit.
      OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD.
      DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled,
      double-blind clinical trial at 67 North American sites consisting of participants
      30 years of age or older who received a diagnosis of PD within 5 years and who
      had the following inclusion criteria: the presence of a rest tremor,
      bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and
      no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria
      included the use of any PD medication within 60 days, the use of any symptomatic
      PD medication for more than 90 days, atypical or drug-induced parkinsonism, a
      Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or
      greater for any limb, a Mini-Mental State Examination score of 25 or less, a
      history of stroke, the use of certain supplements, and substantial recent
      exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible,
      and 18 declined participation. INTERVENTIONS: The remaining 600 participants were
      randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10;
      all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES:
      Participants were observed for 16 months or until a disability requiring
      dopaminergic treatment. The prospectively defined primary outcome measure was the
      change in total UPDRS score (Parts I-III) from baseline to final visit. The study
      was powered to detect a 3-point difference between an active treatment and
      placebo. RESULTS: The baseline characteristics of the participants were well
      balanced, the mean age was 62.5 years, 66% of participants were male, and the
      mean baseline total UPDRS score was 22.7. A total of 267 participants required
      treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received
      2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who
      received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew
      prematurely. Treatments were well tolerated with no safety concerns. The study
      was terminated after a prespecified futility criterion was reached. At study
      termination, both active treatment groups showed slight adverse trends relative
      to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline
      to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49
      relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to
      placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in
      this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00740714.

PMID- 24664243
TI  - Wild bitter gourd protects against alcoholic fatty liver in mice by attenuating
      oxidative stress and inflammatory responses.
AB  - Bitter gourd (Momordica charantia L.) is a common vegetable grown widely in Asia
      that is used as a traditional medicine. The objective of this study was to
      investigate whether wild bitter gourd possessed protective effects against
      chronic alcohol-induced liver injury in mice. C57BL/6 mice were fed an alcohol
      containing liquid diet for 4 weeks to induce alcoholic fatty liver. Meanwhile,
      mice were treated with ethanol extracts from four different wild bitter gourd
      cultivars: Hualien No. 1', Hualien No. 2', Hualien No. 3' and Hualien No. 4'. The
      results indicated that the daily administration of 500 mg kg body weight(-1) of a
      Hualien No. 3' extract (H3E) or a Hualien No. 4' extract (H4E) markedly reduced
      the steatotic alternation of liver histopathology. In addition, the activation of
      serum aminotransferases (AST and ALT) and the accumulation of hepatic TG content
      caused by alcohol were ameliorated. The hepatoprotective effects of H3E and H4E
      involved the enhancement of the antioxidant defence system (GSH, GPx, GRd, CAT
      and SOD), inhibition of lipid peroxidation (MDA) and reduction of pro
      inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) in the liver. Moreover, H3E
      and H4E supplementation suppressed the alcohol-induced elevation of CYP2E1, SREBP
      1, FAS and ACC protein expression. These results demonstrated that ethanol
      extracts of Hualien No. 3' and Hualien No. 4' have beneficial effects against
      alcoholic fatty liver, in which they attenuate oxidative stress and inflammatory
      responses. 

PMID- 24664244
TI  - Interference of Co-amplified nuclear mitochondrial DNA sequences on the
      determination of human mtDNA heteroplasmy by Using the SURVEYOR nuclease and the
      WAVE HS system.
AB  - High-sensitivity and high-throughput mutation detection techniques are useful for
      screening the homoplasmy or heteroplasmy status of mitochondrial DNA (mtDNA), but
      might be susceptible to interference from nuclear mitochondrial DNA sequences
      (NUMTs) co-amplified during polymerase chain reaction (PCR). In this study, we
      first evaluated the platform of SURVEYOR Nuclease digestion of heteroduplexed DNA
      followed by the detection of cleaved DNA by using the WAVE HS System (SN/WAVE-HS)
      for detecting human mtDNA variants and found that its performance was slightly
      better than that of denaturing high-performance liquid chromatography (DHPLC).
      The potential interference from co-amplified NUMTs on screening mtDNA
      heteroplasmy when using these 2 highly sensitive techniques was further examined
      by using 2 published primer sets containing a total of 65 primer pairs, which
      were originally designed to be used with one of the 2 techniques. We confirmed
      that 24 primer pairs could amplify NUMTs by conducting bioinformatic analysis and
      PCR with the DNA from 143B-rho0 cells. Using mtDNA extracted from the
      mitochondria of human 143B cells and a cybrid line with the nuclear background of
      143B-rho0 cells, we demonstrated that NUMTs could affect the patterns of
      chromatograms for cell DNA during SN-WAVE/HS analysis of mtDNA, leading to
      incorrect judgment of mtDNA homoplasmy or heteroplasmy status. However, we
      observed such interference only in 2 of 24 primer pairs selected, and did not
      observe such effects during DHPLC analysis. These results indicate that NUMTs can
      affect the screening of low-level mtDNA variants, but it might not be predicted
      by bioinformatic analysis or the amplification of DNA from 143B-rho0 cells.
      Therefore, using purified mtDNA from cultured cells with proven purity to
      evaluate the effects of NUMTs from a primer pair on mtDNA detection by using PCR
      based high-sensitivity methods prior to the use of a primer pair in real studies
      would be a more practical strategy. 

PMID- 24664245
TI  - In vivo detection of inhalation injury in large airway using three-dimensional
      long-range swept-source optical coherence tomography.
AB  - We report on the feasibility of using long-range swept-source optical coherence
      tomography (OCT) to detect airway changes following smoke inhalation in a sheep
      model. The long-range OCT system (with axial imaging range of 25 mm) and probe
      are capable of rapidly obtaining a series of high-resolution full cross-sectional
      images and three-dimensional reconstructions covering 20-cm length of tracheal
      and bronchial airways with airway diameter up to 25 mm, regardless of the
      position of the probe within the airway lumen. Measurements of airway thickness
      were performed at baseline and postinjury to show mucosal thickness changes
      following smoke inhalation.

PMID- 24664246
TI  - An EGFR/HER2-Bispecific and enediyne-energized fusion protein shows high efficacy
      against esophageal cancer.
AB  - Esophageal cancer is one of the most common cancers, and the 5-year survival rate
      is less than 10% due to lack of effective therapeutic agents. This study was to
      evaluate antitumor activity of Ec-LDP-Hr-AE, a recently developed bispecific
      enediyne-energized fusion protein targeting both epidermal growth factor receptor
      (EGFR) and epidermal growth factor receptor 2 (HER2), on esophageal cancer. The
      fusion protein Ec-LDP-Hr-AE consists of two oligopeptide ligands and an enediyne
      antibiotic lidamycin (LDM) for receptor binding and cell killing, respectively.
      The current study demonstrated that Ec-LDP-Hr had high affinity to bind to
      esophageal squamous cell carcinoma (ESCC) cells, and enediyne-energized fusion
      protein Ec-LDP-Hr-AE showed potent cytotoxicity to ESCC cells with differential
      expression of EGFR and HER2. Ec-LDP-Hr-AE could cause significant G2-M arrest in
      EC9706 and KYSE150 cells, and it also induced apoptosis in ESCC cells in a dosage
      dependent manner. Western blot assays showed that Ec-LDP-Hr-AE promoted caspase-3
      and caspase-7 activities as well as PARP cleavage. Moreover, Ec-LDP-Hr-AE
      inhibited cell proliferation via decreasing phosphorylation of EGFR and HER2, and
      further exerted inhibition of the activation of their downstream signaling
      molecules. In vivo, at a tolerated dose, Ec-LDP-Hr-AE inhibited tumor growth by
      88% when it was administered to nude mice bearing human ESCC cell KYSE150
      xenografts. These results indicated that Ec-LDP-Hr-AE exhibited potent anti-caner
      efficacy on ESCC, suggesting it could be a promising candidate for targeted
      therapy of esophageal cancer. 

PMID- 24664247
TI  - Multi-organ lesions in suckling mice infected with SARS-associated mammalian
      reovirus linked with apoptosis induced by viral proteins MU1 and sigma1.
AB  - We reported the isolation and characterization of a novel mammalian reassortant
      reovirus BYD1 that may have played an accomplice role with SARS-coronavirus
      during the 2003 SARS pandemic. The pathogenic mechanism of this novel reovirus is
      unknown. Reovirus pathogenicity has been associated with virus-induced apoptosis
      in cultured cells and in vivo. The reovirus outer capsid protein MU1 is
      recognized as the primary determinant of reovirus-induced apoptosis. Here, we
      investigated the apoptosis induced by BYD1, its outer capsid protein MU1, and its
      cell-attachment protein sigma1 to understand the pathogenesis of BYD1. We also
      investigated BYD1 caused systemic complications in suckling mice. Under electron
      microscopy, BYD1-infected cells showed characteristics typical of apoptosis.
      Notably, ectopically expressed MU1 and sigma1 induced similar pathological
      apoptosis, independent of BYD1 infection, in host cells in which they were
      expressed, which suggests that MU1 and sigma1 are both apoptotic virulence
      factors. Consistent with previous reports of reovirus pathogenicity, suckling
      mice intracranially inoculated with BYD1 developed central nerve damage,
      myocarditis, and pneumonia. Collectively, our data suggest that BYD1 MU1- and
      sigma1-induced apoptosis is involved in the multi-organ lesions in a suckling
      mouse BYD1 infection model. 

PMID- 24664248
TI  - Is length of shelter stay and receipt of a protection order associated with less
      violence and better functioning for abused women? Outcome data 4 months after
      receiving services.
AB  - To provide differential effectiveness on length of stay at a shelter and receipt
      versus non-receipt of a protection order (PO), and outcomes of violence,
      functioning, and resiliency, in 300 abused women (150 first-time users of a
      shelter and 150 first-time applicants for a PO) who participate in a 7-year study
      with outcomes measured every 4 months. Four months after a shelter stay or
      application for a PO, abused women staying 21 days or less at a shelter reported
      similar outcomes compared with women staying longer than 21 days. Similarly,
      women receiving and not receiving a PO reported overall equivalent outcomes.
      Seeking shelter or justice services results in similar improved outcomes for
      abused women 4 months later, regardless of length of stay at the shelter or
      receipt or no receipt of the PO. Contact with shelter and justice services
      results in positive outcomes for abused women and indicates the urgent need to
      increase availability, accessibility, and acceptability of shelter and justice
      services. 

PMID- 24664249
TI  - Profile and programming needs of federal offenders with histories of intimate
      partner violence.
AB  - This study presents data on male perpetrators of domestic violence (DV) in the
      Correctional Service of Canada (CSC) using two samples: (a) a snapshot of all
      male offenders in CSC who had been assessed for DV (n = 15,166) and (b) a
      cumulative sample of male offenders in CSC from 2002-2010 who had been assessed
      as moderate or high risk for further DV (n = 4,261) DV offenders were compared to
      a cohort sample of non-DV offenders (n = 4,261). Analyses were disaggregated for
      Aboriginal and non-Aboriginal offenders. Results indicated that 40% of the
      federal male population had a suspected history of DV and were therefore screened
      in for in-depth DV risk assessment. Of these, 45% were assessed as moderate or
      high risk for future DV. DV offenders had higher risk and criminogenic need
      ratings, more learning disabilities, more mental health problems, and more
      extensive criminal histories than those without DV histories. Aboriginal DV
      offenders had high levels of alcohol dependence, suggesting a need for substance
      abuse treatment as part of DV programming. Most federal offenders with DV
      histories would be described as belonging to the Antisocial/Generalized
      Aggressive typology and, therefore, adhering to the Risk-Need-Responsivity
      principles of the effective correctional literature, cognitive-behavioral
      treatment that focuses on teaching skills of self-management, and changing
      attitudes supporting relationship violence would be recommended. 

PMID- 24664250
TI  - High-risk sex offenders may not be high risk forever.
AB  - This study examined the extent to which sexual offenders present an enduring risk
      for sexual recidivism over a 20-year follow-up period. Using an aggregated sample
      of 7,740 sexual offenders from 21 samples, the yearly recidivism rates were
      calculated using survival analysis. Overall, the risk of sexual recidivism was
      highest during the first few years after release, and decreased substantially the
      longer individuals remained sex offense-free in the community. This pattern was
      particularly strong for the high-risk sexual offenders (defined by Static-99R
      scores). Whereas the 5-year sexual recidivism rate for high-risk sex offenders
      was 22% from the time of release, this rate decreased to 4.2% for the offenders
      in the same static risk category who remained offense-free in the community for
      10 years. The recidivism rates of the low-risk offenders were consistently low
      (1%-5%) for all time periods. The results suggest that offense history is a
      valid, but time-dependent, indicator of the propensity to sexually reoffend.
      Further research is needed to explain the substantial rate of desistance by high
      risk sexual offenders. 

PMID- 24664251
TI  - Why the impact? Negative affective change as a mediator of the effects of victim
      impact statements.
AB  - Victim impact statements (VISs) represent a contentious legal and psychological
      point of debate. Current knowledge concerning the influence of VISs on jurors'
      emotional states and views of offenders is unclear. Using a sexual assault case,
      the present study attempted to disentangle these points of debate in the body of
      existing literature by (a) examining the direct influences of the presence of a
      VIS and juror Need for Affect (NFA) on sentencing recommendations, (b) assessing
      overall negative affective change as a mediating mechanism of these predictors,
      and (c) if mediation was present, identifying specific negative emotions that
      explain the effects of negative affective change. Results showed that presence of
      a VIS and a greater proclivity to approach emotions were associated with
      significantly greater sentencing recommendations. Moreover, change in negative
      affect mediated the effects of NFA approach and VIS exposure. Examination of
      changes in specific negative emotions revealed that increases in being upset and
      nervous mediated the impact of VIS condition; in addition, increases in hostility
      mediated the effect of NFA approach. Results are discussed with regard to emotion
      based decision making of potential jurors, applications to trial process, and
      future research in the area. 

PMID- 24664252
TI  - Cumulative effects of maternal age and unintended pregnancy on offspring
      aggression.
AB  - Research on physical aggression often points to teen motherhood as being a
      primary contributor in the development of aggressive tendencies among young
      children. As a result of poor parenting practices, limited education, and a lack
      of emotional, physical, and financial resources, children born to young mothers
      often exhibit high levels of aggression across the life course. Meanwhile,
      unintentional pregnancy and young motherhood are likely to share many of the same
      risk factors and negative consequences for offspring, yet there is a dearth of
      research examining pregnancy intentionality and offspring aggression. Using the
      Fragile Families and Wellbeing Study, our study examines how mother's age and
      pregnancy intention status influence aggression among their 5-year-old children.
      We find that young motherhood and unintended births, despite being likely to co
      occur, each provide distinct mechanisms for the formation of aggressive behavior
      in childhood. 

PMID- 24664253
TI  - On the pervasiveness of event-specific alcohol use, general substance use, and
      mental health problems as risk factors for intimate partner violence.
AB  - The aim of this study was to evaluate the role of demographic, mental health, and
      substance use as risk factors for intimate partner violence (IPV). Data were
      derived from Wave II of the National Epidemiological Survey on Alcohol and
      Related Conditions (2004-2005). Eligible participants (N = 25,778) reported
      having an intimate partner 1 year before the survey. Clustered survey
      multivariate multinomial regression methods were used to assess risk factors for
      episodes of IPV. IPV victimization, perpetration, and both victims/perpetrators
      were assessed. Bivariate analyses indicated that African Americans, Hispanics,
      and women were more likely to be victims, perpetrators, or victim/perpetrators as
      compared with men and Whites. Multivariate analyses suggested that having a
      marijuana use disorder was strongly associated with IPV victimization (odds ratio
      [OR] = 2.61) and victim/perpetration (OR = 2.65). Post-traumatic stress disorder
      was consistently associated with all IPV typologies. Depression was associated
      with victimization (OR = 2.00) and IPV victim/perpetration (OR = 1.74).
      Antisocial Personality Disorder and Mania were both related to IPV perpetration
      (ORs = 2.53 and 2.32) and victim/perpetration (ORs = 3.15 and 2.31). Results also
      indicated that alcohol use during episodes of IPV is common (i.e., 35% of those
      who reported IPV also reported that alcohol was involved). Results indicate
      several substance- and mental health-related correlates of IPV. In addition,
      findings indicate that alcohol use by the victim and/or perpetrator is common
      during IPV events. Policy implications and directions for future research are
      discussed. 

PMID- 24664254
TI  - Eosinophilic oesophagitis: investigations and management.
AB  - Eosinophilic oesophagitis (EO) is an immune/antigen mediated, chronic, relapsing
      disease characterised by dysphagia, food bolus impaction and a dense oesophageal
      eosinophilic infiltrate. Characteristic endoscopic features include corrugated
      rings, linear furrows and white exudates, but none are diagnostic. Despite its
      increasing prevalence, EO remains underdiagnosed. There is a strong association
      with other atopic conditions. Symptoms, histology and endoscopic findings can
      overlap with gastro-oesophageal reflux disease. Currently endoscopy and
      oesophageal biopsies are the investigation of choice. Oesophageal physiology
      studies, endoscopic ultrasound, impedance planimetry and serology may have a role
      in the diagnosis and monitoring of response to therapy. Acid reducing medication
      is advocated as first line or adjuvant therapy. Dietary therapy is comprised of
      elimination diets or can be guided by allergen assessment. In adults, topical
      corticosteroids are the mainstay of therapy. Endoscopic dilatation is safe and
      effective for the treatment of non-responsive strictures. Other therapeutic
      options (immunomodulators, biological agents, leukotriene receptor antagonists)
      are under investigation. 

PMID- 24664255
TI  - Determinants of quality of life in advanced kidney disease: time to screen?
AB  - The incidence of older patients with end stage renal disease is on the increase.
      This group of patients have multiple comorbidities and a high symptom burden.
      Dialysis can be life sustaining for such patients. But it is often at the expense
      of quality of life, which starts to decline early in the pathway of chronic
      kidney disease. Quality of life is also important to patients and is a major
      determinant in decisions regarding renal replacement. As a result, validated
      patient-reported outcome measures are increasingly used to assess quality of life
      in renal patients. Cognitive impairment, depression, malnutrition and function
      decline are non-renal determinants of quality of life and mortality. They are
      under-recognised in the renal population but are potentially treatable, if not
      preventable. This review article discusses aetio-pathogenesis, prevalence and
      impact of these four outcomes, advocating regular screening for early
      identification and management. 

PMID- 24664256
TI  - Expression patterns of conserved microRNAs in the male gametophyte of loblolly
      pine (Pinus taeda).
AB  - MicroRNAs (miRNAs) are small RNAs that regulate genes involved in various aspects
      of plant development, but their presence and expression patterns in the male
      gametophytes of gymnosperms have not yet been established. Therefore, this study
      identified and compared the expression patterns of conserved miRNAs from two
      stages of the male gametophyte of loblolly pine (Pinus taeda), which are the
      mature (ungerminated) and germinated pollen. Microarray was used to identify
      conserved miRNAs that varied in expression between these two stages of the
      loblolly pine male gametophyte. Forty-seven conserved miRNAs showed significantly
      different expression levels between mature and germinated loblolly pine pollen.
      In particular, miRNAs representing 14 and 8 families were up- and down-regulated
      in germinated loblolly pine pollen, respectively. qRT-PCR was used to validate
      their expression patterns using representative miRNAs. Target genes and proteins
      were identified using psRNATarget program. Predicted targets of the 22 miRNA
      families belong mostly to classes of genes involved in defense/stress response,
      metabolism, regulation, and signaling. qRT-PCR was also used to validate the
      expression patterns of representative target genes. This study shows that
      conserved miRNAs are expressed in mature and germinated loblolly pine pollen.
      Many of these miRNAs are differentially expressed, which indicates that the two
      stages of the male gametophyte examined are regulated at the miRNA level. This
      study also expands our knowledge of the male gametophytes of seed plants by
      providing insights on some similarities and differences in the types and
      expression patterns of conserved miRNAs between loblolly pine with those of rice
      and Arabidopsis. 

PMID- 24664257
TI  - Pregnancy outcome in women exposed to dopamine agonists during pregnancy: a
      pharmacoepidemiology study in EFEMERIS database.
AB  - PURPOSE: The objective of this exposed-unexposed study was to evaluate potential
      effects of dopamine agonists during pregnancy. METHODS: Data from EFEMERIS, a
      cohort of 57,408 pregnant women living in South West France, were used to compare
      exposed and unexposed women. The exposed group included 183 women (0.3 %) who
      received at least one prescription for one dopamine agonist during pregnancy.
      These women were individually matched with two unexposed women from the cohort
      for age and the month-and-year of the start of pregnancy. Pregnancy losses, birth
      defects, preterm births, low birth weight and psychomotor development were
      studied. RESULTS: Bromocriptine was the most frequently prescribed dopamine
      agonist, followed by cabergoline and quinagolide. Most (75 %) of the dopamine
      agonists were prescribed at the beginning of pregnancy (first trimester). There
      was no difference between the two groups concerning pregnancy history and
      demographic data. After adjustment for potential confounders, prescription and
      dispensation of dopamine agonists was associated with an increased risk of
      pregnancy loss [PORa = 3.7; 95 % confidence interval (CI) 1.8-7.4] and preterm
      birth (PORa = 3.6; 95 % CI 1.5-8.3). The prevalence of birth defects and low
      birth weight was not significantly different between the two groups. No
      difference in psychomotor development at either 9 or 24 months was observed
      between the two groups. CONCLUSION: This study suggests that prenatal exposure to
      dopamine agonists may be associated with an increased risk of pregnancy loss and
      preterm birth.

PMID- 24664258
TI  - Improving postpartum screening rates.

PMID- 24664265
TI  - Optical biosensors with an integrated Mach-Zehnder Interferometer for detection
      of Listeria monocytogenes.
AB  - In this work, we have demonstrated an efficient optical immunoassay technique for
      the detection of a food-borne pathogen, Listeria monocytogenes, using a Mach
      Zehnder Interferometer (MZI) configuration. We have investigated ten different
      MZI configurations with angular and Sbend Y-junction geometries. An efficient
      Hydrofluoric acid (HF) based technique was used for rapid and specific binding of
      L. monocytogenes to the sensor arm of the MZI biosensor. The MZI biosensor was
      able to detect L. monocytogenes at concentrations of the order of 10(5) CFU/ml,
      which is lower than the infection dose for healthy human beings. SEM analysis and
      light intensity measurements showed the biosensor is highly selective to L.
      monocytogenes over other microbial species (such as Escherichia coli). Finally, a
      novel calibration scheme of the MZI biosensor was developed from experimental
      data that can be used for determining unknown concentrations of L. monocytogenes.

PMID- 24664266
TI  - Interventional real-time ultrasound imaging with an integrated electromagnetic
      field generator.
AB  - PURPOSE: Ultrasound (US) guided procedures are frequently performed for diagnosis
      and treatment of many diseases. However, there are safety and procedure duration
      limitations in US-guided interventions due to poor image quality and inadequate
      visibility of medical instruments in the field of view. To address this issue, we
      propose an interventional imaging system based on a mobile electromagnetic (EM)
      field generator (FG) attached to a US probe. METHODS: A standard US probe was
      integrated with an EM FG to allow combined movement of the FG with real-time
      imaging to achieve (1) increased tracking accuracy for medical instruments are
      located near the center of the tracking volume, (2) increased robustness because
      the FG is distant to large metallic objects, and (3) reduced setup complexity
      since time-consuming placement of the FG is not required. The new integrated US
      FG imaging system was evaluated by assessing tracking and calibration accuracy in
      a clinical setting. To demonstrate clinical applicability, the prototype US-EMFG
      probe was tested in needle puncture procedures. RESULTS: The mobile EMFG attached
      to a US probe yielded sub-millimeter tracking accuracy despite the presence of
      metal close to the FG. Calibration errors were in the range of 1-2 mm. In an
      initial phantom study on US-guided needle punctures, targeting errors of about 3
      mm were achieved. CONCLUSION: A combined US-EMFG probe is feasible and effective
      for tracking medical instruments relative to US images with high accuracy and
      robustness while keeping hardware complexity low.

PMID- 24664268
TI  - Vision-based online recognition of surgical activities.
AB  - PURPOSE: Surgical processes are complex entities characterized by expressive
      models and data. Recognizable activities define each surgical process. The
      principal limitation of current vision-based recognition methods is inefficiency
      due to the large amount of information captured during a surgical procedure. To
      overcome this technical challenge, we introduce a surgical gesture recognition
      system using temperature-based recognition. METHODS: An infrared thermal camera
      was combined with a hierarchical temporal memory and was used during surgical
      procedures. The recordings were analyzed for recognition of surgical activities.
      The image sequence information acquired included hand temperatures. This datum
      was analyzed to perform gesture extraction and recognition based on heat
      differences between the surgeon's warm hands and the colder background of the
      environment. RESULTS: The system was validated by simulating a functional
      endoscopic sinus surgery, a common type of otolaryngologic surgery. The thermal
      camera was directed toward the hands of the surgeon while handling different
      instruments. The system achieved an online recognition accuracy of 96% with high
      precision and recall rates of approximately 60%. CONCLUSION: Vision-based
      recognition methods are the current best practice approaches for monitoring
      surgical processes. Problems of information overflow and extended recognition
      times in vision-based approaches were overcome by changing the spectral range to
      infrared. This change enables the real-time recognition of surgical activities
      and provides online monitoring information to surgical assistance systems and
      workflow management systems.

PMID- 24664267
TI  - Optimization of breast mass classification using sequential forward floating
      selection (SFFS) and a support vector machine (SVM) model.
AB  - PURPOSE: Improving radiologists' performance in classification between malignant
      and benign breast lesions is important to increase cancer detection sensitivity
      and reduce false-positive recalls. For this purpose, developing computer-aided
      diagnosis schemes has been attracting research interest in recent years. In this
      study, we investigated a new feature selection method for the task of breast mass
      classification. METHODS: We initially computed 181 image features based on mass
      shape, spiculation, contrast, presence of fat or calcifications, texture,
      isodensity, and other morphological features. From this large image feature pool,
      we used a sequential forward floating selection (SFFS)-based feature selection
      method to select relevant features and analyzed their performance using a support
      vector machine (SVM) model trained for the classification task. On a database of
      600 benign and 600 malignant mass regions of interest, we performed the study
      using a tenfold cross-validation method. Feature selection and optimization of
      the SVM parameters were conducted on the training subsets only. RESULTS: The area
      under the receiver operating characteristic curve [Formula: see text] was
      obtained for the classification task. The results also showed that the most
      frequently selected features by the SFFS-based algorithm in tenfold iterations
      were those related to mass shape, isodensity, and presence of fat, which are
      consistent with the image features frequently used by radiologists in the
      clinical environment for mass classification. The study also indicated that
      accurately computing mass spiculation features from the projection mammograms was
      difficult, and failed to perform well for the mass classification task due to
      tissue overlap within the benign mass regions. CONCLUSION: In conclusion, this
      comprehensive feature analysis study provided new and valuable information for
      optimizing computerized mass classification schemes that may have potential to be
      useful as a "second reader" in future clinical practice.

PMID- 24664269
TI  - Video-guided calibration of an augmented reality mobile C-arm.
AB  - PURPOSE: The augmented reality (AR) fluoroscope augments an X-ray image by video
      and provides the surgeon with a real-time in situ overlay of the anatomy. The
      overlay alignment is crucial for diagnostic and intra-operative guidance, so
      precise calibration of the AR fluoroscope is required. The first and most complex
      step of the calibration procedure is the determination of the X-ray source
      position. Currently, this is achieved using a biplane phantom with movable
      metallic rings on its top layer and fixed X-ray opaque markers on its bottom
      layer. The metallic rings must be moved to positions where at least two pairs of
      rings and markers are isocentric in the X-ray image. The current "trial and
      error" calibration process currently requires acquisition of many X-ray images, a
      task that is both time consuming and radiation intensive. An improved process was
      developed and tested for C-arm calibration. METHODS: Video guidance was used to
      drive the calibration procedure to minimize both X-ray exposure and the time
      involved. For this, a homography between X-ray and video images is estimated.
      This homography is valid for the plane at which the metallic rings are positioned
      and is employed to guide the calibration procedure. Eight users having varying
      calibration experience (i.e., 2 experts, 2 semi-experts, 4 novices) were asked to
      participate in the evaluation. RESULTS: The video-guided technique reduced the
      number of intra-operative X-ray calibration images by 89% and decreased the total
      time required by 59%. CONCLUSION: A video-based C-arm calibration method has been
      developed that improves the usability of the AR fluoroscope with a friendlier
      interface, reduced calibration time and clinically acceptable radiation doses.

PMID- 24664270
TI  - Effect of water-soluble silicon supplementation on bone status and balance of
      calcium and magnesium in male mice.
AB  - Silicon (Si) is important for the growth and development of bone and connective
      tissues. Several studies have reported that Si supplementation improved bone
      mineral density (BMD) in female ovarectomized rats. However, few studies have
      investigated the effects of Si supplementation on bone status and bone metabolism
      in male animals. The purpose of this study was to investigate the effects of Si
      supplementation on BMD and balance of calcium (Ca) and magnesium (Mg) in adult
      male mice. Si was administrated orally through demineralized water containing
      different contents of Si as a form of sodium metasilicate (0 %, control; 0.025 %,
      Si50; 0.050 %, Si100; and 0.075 %, Si150) to 9-week-old male mice for 4 weeks. Si
      supplementation did not alter weight gain or BMD of femur and tibia in male mice.
      However, a high level of Si (0.05 and 0.075 %) supplementation significantly
      decreased Mg retention without changing Ca retention. Serum alkaline phosphatase
      of Si-supplemented groups significantly decreased compared with that of the
      control. According to these results, short-term Si supplementation did not affect
      BMD but showed a possible effect on increasing the need for Mg in adult male
      mice.

PMID- 24664271
TI  - Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin
      resistance.
AB  - In this study, our objective was to evaluating the value of serum zinc levels as
      an etiologic and prognostic marker in patients with polycystic ovarian syndrome.
      We conducted a prospective study, including 53 women with polycystic ovarian
      syndrome and 33 healthy controls. We compared serum zinc levels, as well as
      clinical and metabolic features, of the cases. We also compared serum zinc levels
      between patients with polycystic ovarian syndrome with insulin resistance. Mean
      zinc levels were found to be significantly lower in patients with polycystic
      ovarian syndrome than healthy controls. Multiple logistic regression analysis of
      significant metabolic variables between polycystic ovarian syndrome and control
      groups (serum zinc level, body mass index, the ratio of triglyceride/high-density
      lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most
      significant variable to predict polycystic ovarian syndrome. Mean serum zinc
      levels tended to be lower in patients with polycystic ovarian syndrome with
      impaired glucose tolerance than patients with normal glucose tolerance, but the
      difference was not statistically significant. In conclusion, zinc deficiency may
      play a role in the pathogenesis of polycystic ovarian syndrome and may be related
      with its long-term metabolic complications. 

PMID- 24664272
TI  - Gender differences influence renal injury in cisplatin-treated rats: biochemical
      evaluation.

PMID- 24664273
TI  - Optical trapping and manipulation of plasmonic nanoparticles: fundamentals,
      applications, and perspectives.
AB  - This feature article discusses the optical trapping and manipulation of plasmonic
      nanoparticles, an area of current interest with potential applications in
      nanofabrication, sensing, analytics, biology and medicine. We give an overview
      over the basic theoretical concepts relating to optical forces, plasmon
      resonances and plasmonic heating. We discuss fundamental studies of plasmonic
      particles in optical traps and the temperature profiles around them. We place a
      particular emphasis on our own work employing optically trapped plasmonic
      nanoparticles towards nanofabrication, manipulation of biomimetic objects and
      sensing. 

PMID- 24664275
TI  - External auditory canal and middle ear cholesteatoma and osteonecrosis in
      bisphosphonate-treated osteoporosis patients: a Danish national register-based
      cohort study and literature review.
AB  - Long-term treatment with bisphosphonates against osteoporosis may cause atypical
      femur fractures and osteonecrosis of the jaw. Eight cases of bisphosphonate
      associated osteonecrosis of the external auditory canal area are published. Based
      on Danish national registers, we report a time- and dose-dependent increased risk
      of cholesteatoma in osteoporosis patients treated with bisphosphonates.
      INTRODUCTION: In the recent years, there has been a focus on possible rare side
      effects of bisphosphonates (BPs). Eight cases of BP-associated osteonecrosis of
      the external auditory canal have been reported in the world literature. Our aim
      was to describe the incidence of external auditory canal and middle ear diseases
      in Danish patients exposed to BPs in the treatment of osteoporosis. METHODS: This
      register-based nationwide cohort study was conducted on the Danish population of
      approximately 5.6 million individuals. Patients who were prescribed BP for
      treatment of osteoporosis from 2003 to 2010 (n = 131,794) were included in the
      study and compared with the age- and gender-matched controls, unexposed to BP.
      RESULTS: The overall incidence of cholesteatoma in the ear was low. Only 350
      events were seen in 527,176 cases and controls over 2,826,120.73 observation
      years. Totally, 119 events of cholesteatoma in the ear were recorded after
      initiation of BP therapy, 34 in the external auditory canal and 85 in the middle
      ear. Cholesteatoma in the external auditory canal was more frequent in the
      exposed than in the unexposed group (p < 0.0001). We found a significant dose
      event relationship between incidence of cholesteatoma and dose of alendronate (p
      < 0.0001) and etidronate (p < 0.0001). Furthermore, we found an association
      between duration of treatment with alendronate and etidronate and risk of
      cholesteatoma in the external auditory ear canal (log rank, p = 0.002). No cases
      of bone destruction were observed during the 7-year observation period in either
      group. CONCLUSION: The use of oral BP is associated with an increased risk of
      cholesteatoma of the external auditory canal. The risk is small and associated
      with duration and dosage of BP.

PMID- 24664276
TI  - Coinhibitory suppression of T cell activation by CD40 protects against obesity
      and adipose tissue inflammation in mice.
AB  - BACKGROUND: Costimulatory cascades such as the CD40L-CD40 dyad enhance immune
      cell activation and inflammation during atherosclerosis. Here, we tested the
      hypothesis that CD40 directly modulates traits of the metabolic syndrome in diet
      induced obesity in mice. METHODS AND RESULTS: To induce the metabolic syndrome,
      wild-type or CD40(-/-) mice consumed a high-fat diet for 20 weeks. Unexpectedly,
      CD40(-/-) mice exhibited increased weight gain, impaired insulin secretion,
      augmented accumulation of inflammatory cells in adipose tissue, and enhanced
      proinflammatory gene expression. This proinflammatory and adverse metabolic
      phenotype could be transplanted into wild-type mice by reconstitution with CD40
      deficient lymphocytes, indicating a major role for CD40 in T or B cells in this
      context. Conversely, therapeutic activation of CD40 signaling by the stimulating
      antibody FGK45 abolished further weight gain during the study, lowered glucose
      levels, improved insulin sensitivity, and suppressed adipose tissue inflammation.
      Mechanistically, CD40 activation decreased the expression of proinflammatory
      cytokines in T cells but not in B cells or macrophages. Finally, repopulation of
      lymphocyte-free Rag1(-/-) mice with CD40(-/-) T cells provoked dysmetabolism and
      inflammation, corroborating a protective role of CD40 on T cells in the metabolic
      syndrome. Finally, levels of soluble CD40 showed a positive association with
      obesity in humans, suggesting clinical relevance of our findings. CONCLUSIONS: We
      present the surprising finding that CD40 deficiency on T cells aggravates whereas
      activation of CD40 signaling improves adipose tissue inflammation and its
      metabolic complications. Therefore, positive modulation of the CD40 pathway might
      describe a novel therapeutic concept against cardiometabolic disease.

PMID- 24664277
TI  - Permanent leadless cardiac pacing: results of the LEADLESS trial.
AB  - BACKGROUND: Conventional cardiac pacemakers are associated with several potential
      short- and long-term complications related to either the transvenous lead or
      subcutaneous pulse generator. We tested the safety and clinical performance of a
      novel, completely self-contained leadless cardiac pacemaker. METHODS AND RESULTS:
      The primary safety end point was freedom from complications at 90 days. Secondary
      performance end points included implant success rate, implant time, and measures
      of device performance (pacing/sensing thresholds and rate-responsive
      performance). The mean age of the patient cohort (n=33) was 77+/-8 years, and 67%
      of the patients were male (n=22/33). The most common indication for cardiac
      pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%).
      The implant success rate was 97% (n=32). Five patients (15%) required the use of
      >1 leadless cardiac pacemaker during the procedure. One patient developed right
      ventricular perforation and cardiac tamponade during the implant procedure, and
      eventually died as the result of a stroke. The overall complication-free rate was
      94% (31/33). After 3 months of follow-up, the measures of pacing performance
      (sensing, impedance, and pacing threshold) either improved or were stable within
      the accepted range. CONCLUSIONS: In a prospective nonrandomized study, a
      completely self-contained, single-chamber leadless cardiac pacemaker has shown to
      be safe and feasible. The absence of a transvenous lead and subcutaneous pulse
      generator could represent a paradigm shift in cardiac pacing. CLINICAL TRIAL
      REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT01700244.

PMID- 24664278
TI  - In search of a few good apps.

PMID- 24664279
TI  - Endoplasmic reticulum stress-mediated activation of p38 MAPK, Caspase-2 and
      Caspase-8 leads to abrin-induced apoptosis.
AB  - Abrin from Abrus precatorius plant is a potent protein synthesis inhibitor and
      induces apoptosis in cells. However, the relationship between inhibition of
      protein synthesis and apoptosis is not well understood. Inhibition of protein
      synthesis by abrin can lead to accumulation of unfolded protein in the
      endoplasmic reticulum causing ER stress. The observation of phosphorylation of
      eukaryotic initiation factor 2alpha and upregulation of CHOP (CAAT/enhancer
      binding protein (C/EBP) homologous protein), important players involved in ER
      stress signaling by abrin, suggested activation of ER stress in the cells. ER
      stress is also known to induce apoptosis via stress kinases such as p38 MAPK and
      JNK. Activation of both the pathways was observed upon abrin treatment and found
      to be upstream of the activation of caspases. Moreover, abrin-induced apoptosis
      was found to be dependent on p38 MAPK but not JNK. We also observed that abrin
      induced the activation of caspase-2 and caspase-8 and triggered Bid cleavage
      leading to mitochondrial membrane potential loss and thus connecting the
      signaling events from ER stress to mitochondrial death machinery. 

PMID- 24664280
TI  - Genome-wide analysis of water-stress-responsive microRNA expression profile in
      tobacco roots.
AB  - MicroRNAs (miRNAs) play a pivotal role in post-transcriptional regulation of gene
      expression in plants. In this study, we investigate miRNAs in an agronomically
      important common tobacco in China, named Honghua Dajinyuan (a drought-tolerant
      cultivar). Here, we report a comprehensive analysis of miRNA expression profiles
      in mock-treat grown (CK) and 20 % polyethylene glycol-grown (PEG-grown) tobacco
      roots using a high-throughput sequencing approach. A total of 656 unique miRNAs
      representing 53 miRNA families were identified in the two libraries, of which 286
      unique miRNAs representing 162 microRNAs were differentially expressed. In
      addition, nine differentially expressed microRNAs selected from different
      expressed miRNA family with high abundance were subjected to further analysis and
      validated by quantitative real-time PCR (Q-PCR). In addition, the expression
      pattern of these identified candidate conserved miRNA and target genes of three
      identified miRNA (nta-miR172b, nta-miR156i, and nta-miR160a) were also validated
      by Q-PCR. Gene ontology (GO) enrichment analysis suggests that the putative
      target genes of these differentially expressed miRNAs are involved in metabolic
      process and response to stimulus. In particular, 25 target genes are involved in
      regulating plant hormone signal transduction and metabolism, indicating that
      these association microRNAs may play important regulatory roles in responding to
      PEG resistance. Moreover, this study adds a significant number of novel miRNAs to
      the tobacco miRNome. 

PMID- 24664282
TI  - The development of infants' use of novel verbal information when reasoning about
      others' actions.
AB  - How sophisticated are infants at using novel verbal information when reasoning
      about which of two objects an agent is likely to select? The present research
      examined the development of infants' ability to interpret a change from one novel
      word to another as signaling a possible change in which object the agent would
      choose next. In three experiments, 7- and 12-month-olds were familiarized to an
      event in which they heard a novel word ("A dax!") and then saw an agent reach for
      one of two distinct objects. During test, the infants heard a different novel
      word ("A pilk!") and then saw the agent grasp the same object or the other
      object. At 7 months, infants ignored the change in word and expected the agent to
      continue reaching for the same object. At 12 months, however, infants attended to
      the change in word: They realized that it signaled a possible change in the
      agent's upcoming actions, though they were unable to form a specific expectation
      about what these new actions might be, most likely due to their limited mutual
      exclusivity assumption. Control conditions supported these interpretations.
      Together, these results suggest that by 12 months of age, infants understand not
      only that words are selected for communicative purposes, but also that a change
      from one novel word to another may signal a change in an agent's upcoming
      actions. 

PMID- 24664281
TI  - The role of muscle microRNAs in repairing the neuromuscular junction.
AB  - microRNAs have been implicated in mediating key aspects of skeletal muscle
      development and responses to diseases and injury. Recently, we demonstrated that
      a synaptically enriched microRNA, miR-206, functions to promote maintenance and
      repair of the neuromuscular junction (NMJ); in mutant mice lacking miR-206,
      reinnervation is impaired following nerve injury and loss of NMJs is accelerated
      in a mouse model of amyotrophic lateral sclerosis (ALS). Here, we asked whether
      other microRNAs play similar roles. One attractive candidate is miR-133b because
      it is in the same transcript that encodes miR-206. Like miR-206, miR-133b is
      concentrated near NMJs and induced after denervation. In miR-133b null mice,
      however, NMJ development is unaltered, reinnervation proceeds normally following
      nerve injury, and disease progression is unaffected in the SOD1(G93A) mouse model
      of ALS. To determine if miR-206 compensates for the loss of miR-133b, we
      generated mice lacking both microRNAs. The phenotype of these double mutants
      resembled that of miR-206 single mutants. Finally, we used conditional mutants of
      Dicer, an enzyme required for the maturation of most microRNAs, to generate mice
      in which microRNAs were depleted from skeletal muscle fibers postnatally, thus
      circumventing a requirement for microRNAs in embryonic muscle development.
      Reinnervation of muscle fibers following injury was impaired in these mice, but
      the defect was similar in magnitude to that observed in miR-206 mutants.
      Together, these results suggest that miR-206 is the major microRNA that regulates
      repair of the NMJ following nerve injury. 

PMID- 24664283
TI  - Distinct septin heteropolymers co-exist during multicellular development in the
      filamentous fungus Aspergillus nidulans.
AB  - Septins are important components of the cytoskeleton that are highly conserved in
      eukaryotes and play major roles in cytokinesis, patterning, and many
      developmental processes. Septins form heteropolymers which assemble into higher
      order structures including rings, filaments, and gauzes. In contrast to actin
      filaments and microtubules, the molecular mechanism by which septins assemble is
      not well-understood. Here, we report that in the filamentous fungus Aspergillus
      nidulans, four core septins form heteropolymeric complexes. AspE, a fifth septin
      lacking in unicellular yeasts, interacts with only one of the core septins, and
      only during multicellular growth. AspE is required for proper localization of
      three of the core septins, and requires this same subset of core septins for its
      own unique cortical localization. The DeltaaspE mutant lacks developmentally
      specific septin higher-order structures and shows reduced spore production and
      slow growth with low temperatures and osmotic stress. Our results show that at
      least two distinct septin heteropolymer populations co-exist in A. nidulans, and
      that while AspE is not a subunit of either heteropolymer, it is required for
      assembly of septin higher-order structures found in multicellular development. 

PMID- 24664284
TI  - Molecular diversity of acid-catalyzed one-pot reaction of arylamines, methyl
      propiolate, and isatins.
AB  - Under the catalysis of p-TsOH, beta-enamino esters, generated in situ from the
      reaction of arylamines and propiolate, were reacted with isatins to afford
      isatinylidene bis(3-arylamino)acrylates in moderate yields. When BF3.OEt2 was
      used as catalyst, similar reactions of the in situ generated beta-enamino esters
      resulted in the corresponding spiro[indoline-3,4'-pyridine] derivatives in good
      yields.

PMID- 24664285
TI  - Design, synthesis, and biological evaluation of 2-benzylpyrroles and 2
      benzoylpyrroles based on structures of insecticidal chlorfenapyr and natural
      pyrrolomycins.
AB  - Based on structures of insecticidal chlorfenapyr and antibiotic natural
      pyrrolomycins, a series of new 2-benzylpyrroles and 2-benzoylpyrroles (with or
      without ethoxymethyl group on the nitrogen of pyrrole) were designed and
      synthesized. These compounds or their parent compounds possess weak acidity and
      high lipophilicity, the two characteristic properties for uncouplers of oxidative
      phosphorylation; therefore, they are expected to have insecticidal and acaricidal
      activity. The bioassay result verified that both 2-benzylpyrroles 17 and 2
      benzoylpyrroles 19 had varied degrees of insecticidal activity against oriental
      armyworm depending on the substituents on the benzene ring, but they did not give
      any acaricidal activity. Conversely, most N-alkylated compounds 18 and 20
      exhibited both insecticidal activity and acaricidal activity, of which compound
      18i [4-bromo-2-(2,4-dichlorobenzyl)-1-(ethoxymethyl) -5-(trifluoromethyl) -1H
      pyrrole-3-carbonitrile] has IC50 as low as 10-20 mg L(-1) on both activities.

PMID- 24664286
TI  - Chemopreventive functions and molecular mechanisms of garlic organosulfur
      compounds.
AB  - Garlic (Allium sativum L.) has long been used both for culinary and medicinal
      purposes by many cultures. Population and preclinical investigations have
      suggested that dietary garlic intake has health benefits, such as lowering the
      risk of esophageal, stomach and prostate cancers. Extensive studies from
      laboratory and animal models have revealed that garlic has a wide range of
      biological activities, and garlic organosulfur compounds (OSCs) are responsible
      for the biological activities. However, the presence and potency of garlic OSCs
      vary with respect to the mode of garlic preparation and extraction. Cooked or
      processed garlic products showed different kinds of garlic OSCs, some of which
      are highly unstable and instantly decomposed. These facts, possibly gave
      paradoxical results on the garlic effects. In this review, we first summarized
      the biotransformation processes of garlic alliin into different garlic OSCs as
      well as the garlic OSCs compositions from different garlic preparations. Next, we
      reviewed the chemopreventive functions and molecular mechanisms focusing on the
      anti-inflammation, antioxidation, anti-diabetes and anticancer activity behind
      different garlic OSCs. 

PMID- 24664287
TI  - Association of C-peptide and leptin with prostate cancer incidence in the Health
      Professionals Follow-up Study.
AB  - PURPOSE: Hyperinsulinemia is hypothesized to influence prostate cancer risk.
      Thus, we evaluated the association of circulating C-peptide, which is a marker of
      insulin secretion, and leptin, which is secreted in response to insulin and
      influences insulin sensitivity, with prostate cancer risk. METHODS: We identified
      prostate cancer cases (n = 1,314) diagnosed a mean of 5.4 years after blood draw
      and matched controls (n = 1,314) in the Health Professionals Follow-up Study.
      Plasma C-peptide and leptin concentrations were measured by ELISA. Odds ratios
      (ORs) and 95 % confidence intervals (CI) were estimated taking into account the
      matching factors age and history of a PSA test before blood draw and further
      adjusting for body mass index, diabetes, and other factors. RESULTS: Neither C
      peptide (quartile [Q]4 vs. Q1: OR 1.05, 95 % CI 0.82-1.34, p-trend = 0.95) nor
      leptin (Q4 vs. Q1: OR 0.85, 95 % CI 0.65-1.12, p-trend = 0.14) was associated
      with prostate cancer risk. Further, neither was associated with risk of advanced
      or lethal disease (n = 156 cases; C-peptide: Q4 vs. Q1, OR 1.18, 95 % CI 0.69
      2.03, p-trend = 0.78; leptin: Q4 vs. Q1, OR 0.74, 95 % CI 0.41-1.36, p-trend =
      0.34). CONCLUSIONS: In this large prospective study, circulating C-peptide and
      leptin concentrations were not clearly associated with risk of prostate cancer
      overall or aggressive disease. Well into the PSA era, our findings do not appear
      to be supportive of the hypothesis that hyperinsulinemia influences risk of total
      or aggressive prostate cancer.

PMID- 24664288
TI  - Angiotensin-(1-7).

PMID- 24664289
TI  - Association of central and peripheral blood pressures with intermediate
      cardiovascular phenotypes.
AB  - In conclusion, numerous studies have documented a superior relation of central
      over brachial BP to intermediate cardiovascular phenotypes or cardiovascular
      target organ damage. In general, PP has been more strongly related to vascular
      disease, whereas systolic pressure seems to be a more important determinant of
      LVH. The similarity of findings in a wide variety of patient-based and population
      based studies as well as a broad range of ethnicities supports the robust nature
      of this phenomenon. Although data regarding the superiority of central over
      brachial PP with regard to LV diastolic dysfunction are preliminary, the
      importance of LVH, female sex, and aging as underlying risk factors for HFPEF
      suggests that more extensive evaluation is likely to reveal a stronger relation
      of central than peripheral BP with this additional measure of target organ
      involvement. Finally, limited data suggesting a more important impact of
      reversing hypertensive cardiovascular hypertrophy by lowering central pressure
      for a given brachial pressure require confirmation in larger, longitudinal
      intervention studies.

PMID- 24664290
TI  - Eligibility for renal denervation: experience at 11 European expert centers.
AB  - Based on the SYMPLICITY studies and CE (Conformite Europeenne) certification,
      renal denervation is currently applied as a novel treatment of resistant
      hypertension in Europe. However, information on the proportion of patients with
      resistant hypertension qualifying for renal denervation after a thorough work-up
      and treatment adjustment remains scarce. The aim of this study was to investigate
      the proportion of patients eligible for renal denervation and the reasons for
      noneligibility at 11 expert centers participating in the European Network
      COordinating Research on renal Denervation in treatment-resistant hypertension
      (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office
      blood pressure at screening was 177/96 mm Hg, and the number of blood pressure
      lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The
      proportion of patients eligible for renal denervation according to the SYMPLICITY
      HTN-2 criteria and each center's criteria was 42.5% (95% confidence interval,
      38.0%-47.0%) and 39.7% (36.2%-43.2%), respectively. The main reasons of
      noneligibility were normalization of blood pressure after treatment adjustment
      (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected
      secondary causes of hypertension (11.1%). In conclusion, after careful screening
      and treatment adjustment at hypertension expert centers, only ~40% of patients
      referred for renal denervation, mostly by specialists, were eligible for the
      procedure. The most frequent cause of ineligibility (approximately half of cases)
      was blood pressure normalization after treatment adjustment by a hypertension
      specialist. Our findings highlight that hypertension centers with a record in
      clinical experience and research should remain the gatekeepers before renal
      denervation is considered. 

PMID- 24664291
TI  - Aldosterone dysregulation with aging predicts renal vascular function and
      cardiovascular risk.
AB  - Aging and abnormal aldosterone regulation are both associated with vascular
      disease. We hypothesized that aldosterone dysregulation influences the age
      related risk of renal vascular and cardiovascular disease. We conducted an
      analysis of 562 subjects who underwent detailed investigations under conditions
      of liberal and restricted dietary sodium intake (1124 visits) in the General
      Clinical Research Center. Aldosterone regulation was characterized by the ratio
      of maximal suppression to stimulation (supine serum aldosterone on a liberal
      sodium diet divided by the same measure on a restricted sodium diet). We
      previously demonstrated that higher levels of this Sodium-modulated Aldosterone
      Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation.
      Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess
      basal renal hemodynamics and the renal vascular responses to dietary sodium
      manipulation and angiotensin II infusion. Cardiovascular risk was calculated
      using the Framingham Risk Score. In univariate linear regression, older age
      (beta=-4.60; P<0.0001) and higher SASSI (beta=-58.63; P=0.001) predicted lower
      RPF and a blunted RPF response to sodium loading and angiotensin II infusion. We
      observed a continuous, independent, multivariate-adjusted interaction between age
      and SASSI, where the inverse relationship between SASSI and RPF was most apparent
      with older age (P<0.05). Higher SASSI and lower RPF independently predicted
      higher Framingham Risk Score (P<0.0001) and together displayed an additive
      effect. Aldosterone regulation and age may interact to mediate renal vascular
      disease. Our findings suggest that the combination of aldosterone dysregulation
      and renal vascular dysfunction could additively increase the risk of future
      cardiovascular outcomes; therefore, aldosterone dysregulation may represent a
      modifiable mechanism of age-related vascular disease. 

PMID- 24664292
TI  - Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic
      profile of women with preeclampsia.
AB  - Circulating antiangiogenic factors and proinflammatory cytokines are implicated
      in the pathogenesis of preeclampsia. This study was performed to test the
      hypothesis that steroids modify the balance of inflammatory and proangiogenic and
      antiangiogenic factors that potentially contribute to the patient's evolving
      clinical state. Seventy singleton women, admitted for antenatal corticosteroid
      treatment, were enrolled prospectively. The study group consisted of 45
      hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and
      superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5
      cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were
      obtained before steroids and then serially up until delivery. A clinical severity
      score was designed to clinically monitor disease progression. Serum levels of
      angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth
      factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory
      markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids.
      Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as
      markers of T- and B-cell activation, respectively. Steroid treatment coincided
      with a transient improvement in clinical manifestations of preeclampsia. A
      significant decrease in IL-6 and CRP was observed although levels of sIL-2R and
      IgG remained unchanged. Antenatal corticosteroids did not influence the levels of
      angiogenic factors but ET-1 levels registered a short-lived increase
      poststeroids. Although a reduction in specific inflammatory mediators in response
      to antenatal steroids may account for the transient improvement in clinical signs
      of preeclampsia, inflammation is unlikely to be the major contributor to severe
      preeclampsia or useful for therapeutic targeting. 

PMID- 24664293
TI  - Bilateral renal artery stenosis after renal denervation.

PMID- 24664294
TI  - Variations of microRNAs in human placentas and plasma from preeclamptic
      pregnancy.
AB  - Preeclampsia is a major cause of maternal and fetal mortality and morbidity
      worldwide. The differential expression of several microRNAs (miRNAs) has been
      found in preeclamptic placentas. However, great conflict exists regarding this
      aspect, and detailed examinations have largely been lacking of miRNA profiles in
      different parts of the placenta and in maternal plasma of women with this
      disorder. In this study, a total of 9 downregulated miRNAs (miR-195, miR-223, miR
      218, miR-17, miR-18a, miR-19b1, miR-92a1, miR-379, and miR-411) and 7 upregulated
      miRNAs (miR-210, miR-30a-3p, miR-518b, miR-524, miR-17-3p, miR-151, and miR-193b)
      were identified in severe preeclampsia (sPE) placentas when compared with normal
      pregnant controls. In addition, sampling position in the chorionic or basal plate
      of placenta led to evident variations in differential miRNAs of sPE placentas. In
      a prospective pregnant cohort, we found that the circulating levels of 3 members
      of miR-17-92 cluster (ie, miR-18a, miR-19b1, and miR-92a1) were significantly
      lower, whereas that of miR-210 was higher in sPE patients than those in normal
      controls at gestational weeks 15 to 18 and at term. The results of in situ
      hybridization revealed the localization of miR-18a, miR-92a1, and miR-210 in
      various subtypes of placental trophoblasts and endothelial cells. In human
      trophoblast cell line, HTR8/SVneo cells, miR-18a could promote trophoblast cell
      invasion via targeting and suppressing Smad2 expression. This study provides
      fundamental evidences for exploring the roles of miRNAs in the pathogenesis of
      preeclampsia. 

PMID- 24664295
TI  - Uni- and multivariate models for investigating potential prognostic factors in
      idiopathic sudden sensorineural hearing loss.
AB  - With a worldwide incidence estimated at 8-15 per 100,000 population a year,
      idiopathic sudden sensorineural hearing loss (ISSHL) is a common clinical finding
      for otologists. There is a shortage of information on the clinical factors
      capable of predicting hearing recovery and response to therapy. The aim of the
      present study was to retrospectively investigate the prognostic value of clinical
      variables in relation to hearing recovery, in a cohort of 117 consecutive
      patients with ISSHL. Clinical parameters (signs, symptoms, comorbidities and
      treatments) and audiometric data were analyzed with univariate and multivariate
      statistical approaches for prognostic purposes to identify any correlation with
      hearing recovery, also expressed according to the Wilson criteria. Univariate
      analysis showed that age and hypertension were significantly related to hearing
      outcome (p = 0.004 and p = 0.015, respectively). Elderly patients and those with
      hypertension were at higher risk of experiencing no hearing recovery (OR = 3.25
      and OR = 2.89, respectively). Age was an independent prognostic factor on
      multivariate analysis (p = 0.007). Tinnitus as a presenting symptom showed a
      trend towards an association with hearing recovery (p = 0.07). The treatment
      regimen, the time elapsing between the onset of symptoms and the start of therapy
      (p = 0.34), and the duration of the treatment (p = 0.83) were unrelated to
      recovery on univariate analysis. Among the parameters considered, only age was
      significantly and independently related to hearing outcome. There is a need for
      well-designed, randomized clinical trials to enable an evidence-based protocol to
      be developed for the treatment of ISSHL.

PMID- 24664297
TI  - 'Undiagnosing' neurological disease: how to do it, and when not to.

PMID- 24664296
TI  - Curcumin and vitamin E protect against adverse effects of benzo[a]pyrene in lung
      epithelial cells.
AB  - Benzo[a]pyrene (BaP), a well-known environmental carcinogen, promotes oxidative
      stress and DNA damage. Curcumin and vitamin E (VE) have potent antioxidative
      activity that protects cells from oxidative stress and cellular damage. The
      objectives of the present study were to investigate the adverse effects of BaP on
      normal human lung epithelial cells (BEAS-2B), the potential protective effects of
      curcumin and VE against BaP-induced cellular damage, and the molecular mechanisms
      of action. MTT assay, flow cytometry, fluorescence microplate assay, HPLC, qRT
      PCR, and western blot were performed to analyze cytotoxicity, cell cycle,
      reactive oxygen species (ROS), BaP diol-epoxidation (BPDE)-DNA adducts, gene
      expression, and protein expression, respectively. Curcumin or VE prevented cells
      from BaP-induced cell cycle arrest and growth inhibition, significantly
      suppressed BaP-induced ROS levels, and decreased BPDE-DNA adducts. While CYP1A1
      and 1B1 were induced by BaP, these inductions were not significantly reduced by
      curcumin or VE. Moreover, the level of activated p53 and PARP-1 were
      significantly induced by BaP, whereas this induction was markedly reduced after
      curcumin and VE co-treatment. Survivin was significantly down-regulated by BaP,
      and curcumin significantly restored survivin expression in BaP-exposed cells. The
      ratio of Bax/Bcl-2 was also significantly increased in cells exposed to BaP and
      this increase was reversed by VE co-treatment. Taken together, BaP-induced
      cytotoxicity occurs through DNA damage, cell cycle arrest, ROS production,
      modulation of metabolizing enzymes, and the expression/activation of p53, PARP-1,
      survivin, and Bax/Bcl-2. Curcumin and VE could reverse some of these BaP-mediated
      alterations and therefore be effective natural compounds against the adverse
      effects of BaP in lung cells. 

PMID- 24664298
TI  - Is temporary employment a risk factor for work disability due to depressive
      disorders and delayed return to work? The Finnish Public Sector Study.
AB  - OBJECTIVES: Research on temporary employment as a risk factor for work disability
      due to depression is mixed, and few studies have measured work disability outcome
      in detail. We separately examined the associations of temporary employment with
      (i) the onset of work disability due to depression, (ii) the length of disability
      episodes, and (iii) the recurrence of work disability, taking into account the
      possible effect modification of sociodemographic factors. METHODS: We linked the
      prospective cohort study data of 107 828 Finnish public sector employees to
      national registers on work disability (>9 days) due to depression from January
      2005 to December 2011. RESULTS: Disability episodes were longer among temporary
      than permanent employees after adjustment for age, sex, level of education,
      chronic somatic disease, and history of mental/behavioral disorders [cumulative
      odds ratio (COR) 1.37, 95% confidence interval (95% CI) 1.25-51). The association
      between temporary employment and the length of depression-related disability
      episodes was more pronounced among participants with a low educational level (COR
      1.95, 95% CI 1.54-2.48) and older employees (>52 years; COR 3.67, 95% CI 2.83
      4.76). The association was weaker in a subgroup of employees employed for >= 50%
      of the follow-up period (95% of the original sample). Temporary employment was
      not associated with the onset or recurrence of depression-related work
      disability. CONCLUSIONS: Temporary employment is associated with slower return to
      work, indicated by longer depression-related disability episodes, especially
      among older workers and those with a low level of education. Continuous
      employment might protect temporary employees from prolonged work disability.

PMID- 24664300
TI  - Assessing upper limb function in multiple sclerosis.
AB  - The need to fully assess upper limb function in multiple sclerosis (MS) has
      become increasingly clear with recent studies revealing a high prevalence of
      upper limb dysfunction in persons with MS leading to increased dependency and
      reduced quality of life. It is important that clinicians and researchers use
      tailored outcome measures to systematically describe upper limb (dys)function and
      evaluate potential deterioration or improvement on treatment. This topical review
      provides a comprehensive summary of currently used upper limb outcome measures in
      MS, classified according to the levels of the International Classification of
      Functioning (ICF). The clinical utility, strengths, weaknesses and psychometric
      properties of common upper limb outcome measures are discussed. Based on this
      information, recommendations for selecting appropriate upper limb outcome
      measures are given. The current shortcomings in assessment which need to be
      addressed are identified.

PMID- 24664301
TI  - Retraction note: 'Surgical selection for late pancreatic head carcinoma without
      gastric outlet obstruction'.

PMID- 24664303
TI  - If only electronic cigarettes were effective smoking cessation devices.

PMID- 24664302
TI  - Divergent levels of LBP and TGFbeta1 in murine MSCs lead to heterogenic response
      to TLR and proinflammatory cytokine activation.
AB  - The outstanding heterogeneity of stem cell populations is a major obstacle on the
      way to their clinical application. It is therefore paramount to identify the
      molecular mechanisms that underlay this heterogeneity. Individually derived bone
      marrow mesenchymal stromal cells (MSCs) preparations, studied here, diverged
      markedly in various properties, despite of being all tripotent in their
      differentiation potential. Microarray analysis showed that MSC diversity is
      evident also in highly variable gene expression patterns. Differentially
      expressed genes were significantly enriched in toll-like receptors (TLRs) and
      differentiation pathways. Marked differences were observed in LPS binding protein
      (LBP) and transforming growth factor (TGF)beta1 expression. These differences
      correlated with MSC functionality. Therefore, the possible contribution of these
      molecules to MSC diversity was examined. In the TLR signaling pathway, LBP levels
      predicted the ability of specific MSCs to secrete interleukin (IL)-6 in response
      to LPS. A relatively higher expression of TGFbeta1 endowed MSCs with a capacity
      to respond to IL-1beta by reduced osteogenic differentiation. This study thus
      demonstrates major diversity within MSC isolates, which appears early on
      following derivation and persists following long-term culture. MSC heterogeneity
      results from highly variable transcriptome. Differential expression of LBP and
      TGFbeta1, along with other genes, in different MSC preparations, produces the
      variable responses to external stimuli. 

PMID- 24664304
TI  - Apoptotic, inflammatory, and fibrogenic effects of two different types of multi
      walled carbon nanotubes in mouse lung.
AB  - There is increasing concern about the toxicity of inhaled multi-walled carbon
      nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type
      involved in the clearance of inhaled particulate materials, and induction of
      apoptosis in these cells has been considered to contribute to the development of
      lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic
      potential of two types of MWCNTs, characterised by a contrasting average tube
      length and entanglement/agglomeration. Both nanotube types triggered H2O2
      formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen
      with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse
      lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA
      expression of matrix metalloproteinase-8 and tissue inhibitor of
      metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic
      protein-1) response. Masson trichrome staining also revealed epithelial cell
      hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved
      caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid
      MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT.
      However, staining was merely localised to granulomatous foci, and neither of the
      MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7
      cells. In addition, our study reveals that the inflammatory and pro-fibrotic
      effects of MWCNTs in the mouse lung can vary considerably depending on their
      composition. The in vitro analysis of macrophage apoptosis appears to be a poor
      predictor of their pulmonary hazard. 

PMID- 24664305
TI  - Update of molecular pathobiology in oral cancer: a review.
AB  - Head and neck cancer including oral squamous cell carcinoma (OSCC) is the sixth
      most common cancer in the world. OSCC has a high potential for local invasion and
      nodal metastasis, and the overall 5-year survival rate has not significantly
      changed during the past 30 years. Recent research has elucidated the detailed
      molecular mechanisms of carcinogenesis, tumor progression, and metastasis of
      OSCC. It is generally accepted that OSCC arises from multiple genetic alterations
      caused by chronic exposure to carcinogens such as alcohol, smoking, viral
      infections, and inflammation. The molecular mechanisms of carcinogenesis, tumor
      progression, and metastasis of head and neck cancer have been elucidated by
      recent advances in molecular biology. However, many unsolved questions remain. In
      this review, we describe the current molecular biological findings such as human
      papillomavirus infection, epithelial-mesenchymal transition, microRNA, and our
      novel molecular pathological findings of OSCC.

PMID- 24664306
TI  - Clinical features of long-term survivors of recurrent epithelial ovarian cancer.
AB  - BACKGROUND: Although recurrent epithelial ovarian cancer (EOC) is generally
      regarded as an incurable disease, some patients survive more than 5 years after
      the first recurrence. The aim of this study was to evaluate the clinical features
      of patients with recurrent EOC who achieve long-term survival. METHODS: We
      retrospectively reviewed the medical records of 164 patients with recurrent EOC
      and analyzed the clinical stage, histologic subtype, primary treatment, disease
      free interval (DFI), recurrence site, secondary treatment, and overall survival
      from the time of the first recurrence (R-OS), using the Kaplan-Meier method and
      the log-rank test. RESULTS: The median R-OS for all 164 patients was 25 months
      and the 5-year R-OS rate was 25.4 %. There were no significant differences in R
      OS according to the disease stage. The median R-OS was significantly shorter in
      the 6-12-month DFI group (23 months) than in the >=12-month DFI group (61 months)
      (p = 0.0002), while there was no significant difference between the 6-12 and 3-6
      month DFI groups (20 months) (p = 0.161). Of the 164 patients, only 14 survived
      >5 years after the first recurrence. Most of them underwent surgery and/or
      radiotherapy in combination with chemotherapy and underwent >18 cycles of
      platinum-based chemotherapy throughout their treatments (median 22 cycles; range
      4-44). CONCLUSIONS: If high sensitivity to platinum is maintained, patients with
      recurrent EOC may have prolonged survival following repeated platinum-based
      chemotherapy cycles. Moreover, their prognosis improves when chemotherapy is
      combined with secondary cytoreductive surgery and/or irradiation.

PMID- 24664309
TI  - Mononeuritis multiplex: association with infectious condition and familial
      background in a tropical environment: a case report.
AB  - Mononeuritis multiplex is characterized by an asymmetric pattern with affection
      of the peripheral nervous system; this form of polyneuropathy is often seen in
      non-systemic vasculitis. We present a case of multiplex neuropathy in a patient
      with histologicaly verified Hailey-Hailey disease. With the exception of this
      comorbidity--in its characteristic form presenting additionally with a
      superinfected subdermal node--we did not find any other possible etiologic factor
      possibly causative of multiplex neuritis. The diagnosis was confirmed by
      electrophysiological testing. To our knowledge, this is the first case report
      indicating a possible relationship between Hailey-Hailey disease and multiplex
      neuritis. There exists only one related study in the literature, which was
      conducted in Columbia--our patient's home country. This study delineates a
      clinically similar dermal disease (pemphigus foliaceus) in patients from rural
      Colombia (El Bagre). The authors detected anti-neuronal antibodies which were
      interpreted to be responsible for the pathognomonic burning sensations.

PMID- 24664308
TI  - The primary transcriptome of Salmonella enterica Serovar Typhimurium and its
      dependence on ppGpp during late stationary phase.
AB  - We have used differential RNA-seq (dRNA-seq) to characterise the transcriptomic
      architecture of S. Typhimurium SL1344, and its dependence on the bacterial
      alarmone, guanosine tetraphosphate (ppGpp) during late stationary phase, (LSP).
      Under LSP conditions we were able to identify the transcriptional start sites
      (TSSs) for 53% of the S. Typhimurium open reading frames (ORFs) and discovered
      282 candidate non-coding RNAs (ncRNAs). The mapping of LSP TSSs enabled a
      detailed comparison with a previous dRNA-seq study of the early stationary phase
      (ESP) transcriptional architecture of S. Typhimurium SL1344 and its dependence on
      ppGpp. For the purposes of this study, LSP was defined as an aerobic LB culture
      grown to a later optical density reading (OD600 = 3.6) compared to ESP (OD600 =
      2.3). The precise nucleotide positions of the majority of S. Typhimurium TSSs at
      LSP agreed closely with those identified at ESP. However, the identification of
      TSSs at different positions, or where additional or fewer TSSs were found at LSP
      compared to ESP enabled the genome-wide categorisation of growth phase dependent
      changes in promoter structure, the first time such an analysis has been done on
      this scale. Comparison of the ppGpp-dependency LSP and ESP TSSs for mRNAs and
      ncRNAs revealed a similar breadth of ppGpp-activation and repression. However, we
      note several ncRNAs previously shown to be involved in virulence were highly
      ppGpp-dependent at LSP. Finally, although SPI1 was expressed at ESP, we found
      SPI1 was not as highly expressed at LSP, instead we observed elevated expression
      of SPI2 encoded genes. We therefore also report an analysis of SPI2
      transcriptional architecture at LSP resulting in localisation of SsrB binding
      sites and identification of a previously unreported SPI2 TSS. We also show that
      ppGpp is required for nearly all of SPI2 expression at LSP as well as for
      expression of SPI1 at ESP. 

PMID- 24664310
TI  - Acute kidney injury with medazepam-hyoscine buthylbromide.
AB  - An 84-year-old female patient was admitted to our internal medicine outpatient
      clinic complaining of stomach ache, nausea, and vomiting. She had hepatitis C
      infection for 10 years that was managed with antiviral treatment. On the second
      day of admission, she developed anxiety and complained about dysuria. Medazepam
      and hyoscine butylbromide combined tablet was administered. The day after
      medazepam and hyoscine butylbromide administration, patient's creatinine level
      increased to 2.3 mg/dL (0.57-1.11 mg/dL). Medazepam and hyoscine butylbromide
      administration was stopped on the fourth day. After 10 days of follow-up, her
      creatinine levels were normalized. In this article, we present an elderly patient
      with acute kidney injury induced by medazepam and hyoscine butylbromide that was
      managed with best supportive care. 

PMID- 24664307
TI  - Molecular pathways: adaptive kinome reprogramming in response to targeted
      inhibition of the BRAF-MEK-ERK pathway in cancer.
AB  - The central role of the BRAF-MEK-ERK pathway in controlling cell fate has made
      this pathway a primary target for deregulated activation in cancer. BRaf is
      activated by Ras proteins allowing Ras oncogenes to constitutively activate the
      pathway. Activating BRaf mutations are also frequent in several cancers, being
      the most common oncogenic mutation in thyroid carcinoma and melanoma. There are
      currently two inhibitors, vemurafenib and dabrafenib, approved for treatment of
      malignant melanoma having activating BRaf mutations. Concurrent administration of
      BRAF and MAP-ERK kinase (MEK) inhibitor (trametinib) is significantly more active
      in patients with BRAF-mutant melanoma than either single agent alone, but
      progression to resistance ultimately occurs by different mechanisms that increase
      the activation of extracellular signal-regulated kinase (ERK). Such adaptive
      changes in tumor cell signaling networks allow bypass of targeted oncoprotein
      inhibition. This is true with targeted inhibitors for BRaf and MEK as well as
      specific inhibitors for AKT, mTOR, and many receptor tyrosine kinases such as EGF
      receptor (EGFR) and HER2. It is this adaptive response to targeted kinase
      inhibitors that contributes to the failure of single-agent kinase inhibitors to
      have durable responses. This failure is seen in virtually all cancers treated
      with single-agent kinase inhibitors, most of which are not as dependent on a
      single signaling pathway such as BRaf-MEK-ERK in melanoma. Thus, understanding
      the breadth of adaptive reprogramming responses to specific targeted kinase
      inhibition will be critical to develop appropriate combination therapies for
      durable clinical responses.

PMID- 24664311
TI  - Life-threatening heat stroke presenting with ST elevations: a report of
      consecutive cases during the heat wave in Austria in July 2013.
AB  - Heat stroke is a life-threatening condition due to an acute thermoregulatory
      failure during exposure to high environmental temperatures. We report a series of
      four cases (three exertional, one classic heat stroke) during the heat wave of
      July 2013 in Austria. All of them presented with a core temperature > 41  degrees
      C, central nervous dysfunction, acute respiratory and renal failure, disseminated
      intravascular coagulation, rhabdomyolysis, and severe electrocardiographic
      changes, two cases even mimicking ST-elevation myocardial infarction. The
      patients were cooled to normal temperature with the "Arctic sun" external cooling
      system within hours. Electrocardiographic changes resolved quickly. All patients
      primarily recovered from multiple organ dysfunction and could be discharged from
      intensive care unit. Unfortunately, the two elder patients died 1 week and 5
      weeks later because of late complications. 

PMID- 24664313
TI  - Electrochemical properties of micron-sized, spherical, meso- and macro-porous
      Co3O4 and CoO-carbon composite powders prepared by a two-step spray drying
      process.
AB  - Micron-sized, spherical, meso- and macro-porous Co3O4 and CoO-carbon composite
      powders were prepared via a simple two-step spray drying process. The CoO-carbon
      composite powders, in which homogeneous mixing of the metal oxide and carbon
      components was achieved using the first spray drying process, were wet milled to
      produce the slurry for the second spray drying process. Co3O4 and CoO-carbon
      composite powders with mean particle sizes of 4.4 and 4.7 MUm were respectively
      obtained by spray-drying the slurry after post-treatment at 400  degrees C under
      air and nitrogen atmospheres. Meso- and macro-pores were uniformly distributed
      inside the Co3O4 and CoO-carbon composite powders. The CoO-carbon composite
      powders exhibited discharge capacities of 882 and 855 mA h g(-1) at a high
      constant current density of 1400 mA g(-1) for the 2(nd) and 100(th) cycles. The
      discharge capacities of the Co3O4 powders at the 2(nd) and 100(th) cycles were
      970 and 644 mA h g(-1). With stepwise increment in the current density from 500
      to 5000 mA g(-1), the discharge capacities of the CoO-carbon composite powders
      decreased slightly from 985 to 698 mA h g(-1). The superior rate and cycling
      performances of the CoO-carbon composite powders are ascribed to their meso- and
      macro-porous structures and carbon components. 

PMID- 24664312
TI  - Is a complete blood cell count useful in determining the prognosis of pulmonary
      embolism?
AB  - BACKGROUND: Pulmonary embolism (PE) is the third cardiovascular cause of hospital
      admission, following acute coronary syndrome and stroke. Despite high-tech
      diagnostic methods and new treatment modalities, PEs continue to have a high
      mortality rate within the first 3 months. This study was designed to assess the
      additional prognostic value of a complete blood cell count, renal function
      markers, C-reactive protein, and simplified pulmonary embolism severity index
      (sPESI) scoring system in PE 100-day mortality. MATERIALS AND METHODS: The study
      retrospectively enrolled 208 consecutive patients who were hospitalized with the
      diagnosis of an acute PE. The patients' demographic characteristics and clinical
      and laboratory parameters were recorded from the hospital electronic database and
      patient's case notes. The primary end point of the study was an adverse 100-day
      outcome, defined as death from any cause. RESULTS: The all-cause mortality in the
      first 100 days was 14.42 %. The mean age was 57.87 +/- 18.17 (range: 16-93)
      years. We included 79 (38 %) male and 129 (62 %) female individuals. Red cell
      distribution width (RDW) and sPESI were found to be statistically significant
      predictors of PE mortality by multivariate regression analysis. On multivariate
      regression analysis, RDW was associated with a 4.08-fold (95 % confidence
      interval: 1.229-13.335, P = 0.021) increase in PE mortality. CONCLUSION: The
      results of this study demonstrated that RDW and sPESI may be a useful guide in
      predicting 100-day mortality. The elevated RDW may alert physicians to possible
      poor prognosis.

PMID- 24664314
TI  - Vinyl chloride monomer (VCM) induces high occurrence of neural tube defects in
      embryonic mouse brain during neurulation.
AB  - The aim of this study was to explore the direct embryonic teratogenicity of vinyl
      chloride monomer (VCM), especially the toxic effects on the early development of
      the nervous system and its underlying mechanisms. Pregnant mice at embryonic day
      6.5 (E6.5) were injected with different doses of VCM (200, 400 and 600 mg/kg) and
      embryos were harvested at E10.5. Our results showed that doses higher than 400
      mg/kg of VCM increased the incidence of malformed embryos, especially the neural
      tube defects (NTDs). In addition, high-dose of VCM decreased mitotic figure
      counts in the neuroepithelium and enhanced the percentage of cells in G0/G1
      phase, while they were reduced in S phase. The more VCM was injected into mice,
      the fewer positive PCNA cells were seen and the more positive TUNEL cells were
      observed in the neuroepithelium. Moreover, significant increases in the levels of
      caspase-3 protein were observed in NTD embryos. Our results demonstrate that
      during early pregnancy, exposure to doses higher than 400 mg/kg of VCM increases
      the incidence of malformations and particularly the rate of NTDs. High-dose of
      VCM inhibits the proliferation of neural cells and induces cell apoptosis,
      leading to an imbalance in the ratio of proliferation and apoptosis. Meanwhile,
      the apoptosis of neuroepithelial cells might be accelerated by the activation of
      the caspase-3 pathway, and it might be a reason for NTDs.

PMID- 24664315
TI  - Severe H7N9 infection is associated with decreased antigen-presenting capacity of
      CD14+ cells.
AB  - The outbreak of H7N9 human infection has caused concern worldwide, but the
      immunological characteristics of infected patients and the determinants of
      diverse outcomes remain to be thoroughly understood. In this study, twenty-three
      patients with H7N9 infections were classified into severe and mild cases. We
      found that severe patients were commonly lymphopenic with significantly lower
      levels of T cells, monocytes and related cytokine levels compared to the mild
      cases. The expression of HLA-DR on CD14+ cells were significantly lower in the
      severe infection group compared to the mild group (in acute phase: 34.65+/-4.88
      vs. 10.37+/-1.69, p<0.001). Importantly, the expression of HLA-DR on CD14+ cells
      was negatively correlated with H7N9 infection severity. Furthermore, although the
      phagocytosis capabilities of monocyte were similar between two groups, the
      monocytes of severe infection patients had a lower antigen-presenting capacity.
      And some in vitro experiments suggested that the impaired antigen-presenting
      function is associated with lower activation of T cells in responses to immune
      stimulation. Our present study suggested that the severe H7N9 patients were in a
      state of immune decrease which presented with general lymphopenia and low antigen
      presenting capacity resulting in impaired T cell response. Additionally, HLA-DR
      levels of CD14+ cells may be a potential biomarker for predicting H7N9 disease
      progression. 

PMID- 24664316
TI  - Molecular cloning and characterization of genistein 4'-O-glucoside specific
      glycosyltransferase from Bacopa monniera.
AB  - Health related benefits of isoflavones such as genistein are well known.
      Glycosylation of genistein yields different glycosides like genistein 7-O
      glycoside (genistin) and genistein 4'-O-glycoside (sophoricoside). This is the
      first report on isolation, cloning and functional characterization of a
      glycosyltransferase specific for genistein 4'-O-glucoside from Bacopa monniera,
      an important Indian medicinal herb. The glycosyltransferase from B. monniera
      (UGT74W1) showed 49% identity at amino acid level with the glycosyltransferases
      from Lycium barbarum. The UGT74W1 sequence contained all the conserved motifs
      present in plant glycosyltransferases. UGT74W1 was cloned in pET-30b (+)
      expression vector and transformed into E. coli. The molecular mass of over
      expressed protein was found to be around 52 kDa. Functional characterization of
      the enzyme was performed using different substrates. Product analysis was done
      using LC-MS and HPLC, which confirmed its specificity for genistein 4'-O
      glucoside. Immuno-localization studies of the UGT74W1 showed its localization in
      the vascular bundle. Spatio-temporal expression studies under normal and stressed
      conditions were also performed. The control B. monniera plant showed maximum
      expression of UGT74W1 in leaves followed by roots and stem. Salicylic acid
      treatment causes almost tenfold increase in UGT74W1 expression in roots, while
      leaves and stem showed decrease in expression. Since salicylic acid is generated
      at the time of injury or wound caused by pathogens, this increase in UGT74W1
      expression under salicylic acid stress might point towards its role in defense
      mechanism.

PMID- 24664320
TI  - Simulating the digestion of lipid-based drug delivery systems (LBDDS): overview
      of in vitro lipolysis models.
AB  - One of the greatest challenges in the pharmaceutical science is the improvement
      of oral bioavailability of poorly soluble drugs. Lately, one of the most
      attractive approaches has been formulation of lipid based drug delivery systems.
      However, the emerging popularity of these systems in the last decade has brought
      to light the need for efficient methods for their in vitro evaluation that would
      serve as their in vivo behaviour prediction tool. Because lipids are subject to
      lipid digestion and multiple absorption pathways in vivo, simple dissolution
      tests are not predictive enough when testing lipid based delivery systems. To
      assert these needs, the in vitro lipolysis model has been developed, utilizing
      pancreatic enzymes, bile and phospholipids in a temperature controlled chamber to
      simulate in vivo digestion. However, with very variable physiological conditions
      in gastrointestinal tract, this model has not been yet standardised and
      experiments vary among different laboratories. This review discusses in vivo
      events following oral application of lipid based delivery, in vitro lipolysis
      models to emulate them and their future perspectives. 

PMID- 24664321
TI  - Orthogonal projection to latent structures combined with artificial neural
      networks in non-destructive analysis of ebastine powder.
AB  - A new method orthogonal projection to latent structures (O-PLS) combined with
      artificial neural networks is investigated for non-destructive determination of
      ebastine powder via near-infrared (NIR) spectroscopy. The modern NIR spectroscopy
      is efficient, simple and non-destructive technique, which has been used in
      chemical analysis in diverse fields. Being a preprocessing method, O-PLS provides
      a way to remove systematic variation from an input data set X not correlated to
      the response set Y, and does not disturb the correlation between X and Y. In this
      paper, O-PLS pretreated spectral data was applied to establish the ANN model of
      ebastine powder, in this model, the concentration of ebastine as the active
      component was determined. The degree of approximation was employed as the
      selective criterion of the optimum network parameters. In order to compare the
      OPLS-ANN model, the calibration models that use first-derivative and second
      derivative preprocessing spectra were also designed. Experimental results showed
      that the OPLS-ANN model was the best. 

PMID- 24664317
TI  - Tracing the evolution of amniote chromosomes.
AB  - A great deal of diversity in chromosome number and arrangement is observed across
      the amniote phylogeny. Understanding how this diversity is generated is important
      for determining the role of chromosomal rearrangements in generating phenotypic
      variation and speciation. Gaining this understanding is achieved by
      reconstructing the ancestral genome arrangement based on comparisons of genome
      organization of extant species. Ancestral karyotypes for several amniote lineages
      have been reconstructed, mainly from cross-species chromosome painting data. The
      availability of anchored whole genome sequences for amniote species has increased
      the evolutionary depth and confidence of ancestral reconstructions from those
      made solely from chromosome painting data. Nonetheless, there are still several
      key lineages where the appropriate data required for ancestral reconstructions is
      lacking. This review highlights the progress that has been made towards
      understanding the chromosomal changes that have occurred during amniote evolution
      and the reconstruction of ancestral karyotypes. 

PMID- 24664319
TI  - Significance of AT1 receptor independent activation of mineralocorticoid receptor
      in murine diabetic cardiomyopathy.
AB  - BACKGROUND: Diabetes mellitus (DM) has deleterious influence on cardiac
      performance independent of coronary artery disease and hypertension. The
      objective of the present study was to investigate the role of the renin
      angiotensin-aldosterone system, especially angiotensin II type 1a receptor
      (AT1aR) and mineralocorticoid receptor (MR) signaling, in left ventricular (LV)
      dysfunction induced by diabetes mellitus (DM). METHODS AND RESULTS: DM was
      induced by intraperitoneal injection of streptozotocin (200 mg/kg BW) in wild
      type (WT) or AT1aR knockout (KO) male mice, and they were bred during 6 or 12
      weeks. Some KO mice were administered the MR antagonist eplerenone (100 mg/kg
      body weight). At 6 weeks, LV diastolic function was impaired in WT-DM, but
      preserved in KO-DM. At that time point MR mRNA expression was upregulated, NADPH
      oxidase subunit (p47phox) and glutathione peroxidase (GPx1) mRNA expression were
      upregulated, the staining intensities of LV tissue for 4-hydroxy-2-nonenal was
      stronger in immunohistochemistry, the number of terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL) positive cells was increased,
      Bcl-2 protein expression was significantly downregulated, and the expression of
      SERCA2a and phosphorylated phospholamban was depressed in WT-DM, while these
      changes were not seen in KO-DM. At 12 weeks, however, these changes were also
      noted in KO-DM. Eplerenone arrested those changes. The plasma aldosterone
      concentration was elevated in WT-DM but not in KO-DM at 6 weeks. It showed 3.7
      fold elevation at 12 weeks even in KO-DM, which suggests "aldosterone
      breakthrough" phenomenon. However, the aldosterone content in LV tissue was
      unchanged in KO-DM. CONCLUSIONS: DM induced diastolic dysfunction was observed
      even in KO at 12 weeks, which was ameliorated by minelarocorticoid receptor
      antagonist, eplerenone. AT1-independent MR activation in the LV might be
      responsible for the pathogenesis of diabetic cardiomyopathy.

PMID- 24664318
TI  - A requiem to the nuclear matrix: from a controversial concept to 3D organization
      of the nucleus.
AB  - The first papers coining the term "nuclear matrix" were published 40 years ago.
      Here, we review the data obtained during the nuclear matrix studies and discuss
      the contribution of this controversial concept to our current understanding of
      nuclear architecture and three-dimensional organization of genome.

PMID- 24664322
TI  - Amperometric biosensor for xanthine determination based on Fe3O4 nanoparticles.
AB  - An amperometric xanthine biosensor was developed based on the immobilization of
      xanthine oxidase (XO) into the Fe3O4 nanoparticles modified carbon paste.
      Electron transfer properties of unmodified and Fe3O4 nanoparticles modified
      carbon paste electrodes were investigated by cyclic voltammetry and
      electrochemical impedance spectroscopy. Fe3O4 nanoparticles increased
      electroactive surface area of the electrode and electron transfer at
      solution/electrode interface. Optimum pH, nanoparticle loading and enzyme loading
      were found to be 6.0; 14.2% and 0.6 Unit XO respectively. Fe3O4 nanoparticles
      modified carbon paste enzyme electrode allowed xanthine determination at -0.20 V,
      thus minimizing the potential interferences from electrochemically oxidizable
      substances such as ascorbic acid and uric acid. A linear relationship was
      obtained in the concentration range from 7.4 * 10-7 mol L-1 to 7.5 * 10-5 mol L-1
      and a detection limit of 2.0 * 10-7 mol L-1. The biosensor was used for
      determination of xanthine in urine samples and the results indicate that the
      biosensor is effective for the detection of xanthine. 

PMID- 24664323
TI  - New type of chitosan/2-hydroxypropyl-beta-cyclodextrin composite membrane for
      gallic acid encapsulation and controlled release.
AB  - A new type of chitosan/2-hydroxypropyl-beta-cyclodextrin composite membrane have
      been developed for the encapsulation and controlled release of gallic acid. The
      morphology of the composite membrane was investigated by infrared spectroscopy
      (FT-IR) and scanning electron microscopy (SEM), whereas swelling gallic acid and
      release properties were investigated by UV-visible spectroscopy. The release
      behavior with pH changes was also explored. The composite membrane based on
      chitosan/2-hydroxypropyl-beta-cyclodextrin with gallic acid included showed
      improved antioxidant capacities compared to plain chitosan membrane. The
      information obtained in this study will facilitate the design and preparation of
      composite membrane based on chitosan and could open a wide range of applications,
      particularly its use as an antioxidant in food, food packaging, biomedical
      (biodegradable soft porous scaffolds for enhance the surrounding tissue
      regeneration), pharmaceutical and cosmetics industries. 

PMID- 24664324
TI  - Lattice enthalpies, polarizabilities and shear moduli of lanthanide
      orthophosphates LnPO4.
AB  - Lattice energies DeltaLHtheta of lanthanide orthophosphates, LnPO4 (Ln=Ce-Lu,
      excluding Pm) have been determined from the Born-Haber cycle and compared with
      those calculated by other methods. The Born-Haber cycle results in close values
      of DeltaLHtheta to those obtained after an empirical equation proposed by Glasser
      and Jenkins. It has been found that: (i) the partial derivative of the lattice
      enthalpies to the molar volumes corresponds by dimension and magnitude to the
      shear moduli of these crystals; (ii) these moduli differ for the monazite- and
      xenotime-type structures of LnPO4. Molar polarizabilities have been calculated
      for three LnPO4 with monazite structure, Ln=Ce, Nd, Sm, and for three LnPO4 with
      xenotime structure, Ln=Tb, Dy, Yb.

PMID- 24664325
TI  - Synthesis and characterization of alkylammonium zwitterionic amino acids
      derivatives by FTIR, NMR spectroscopy and DFT calculations.
AB  - 3-(3-Dimethylammonio)propylammonio propanoate bromide (1), 4-(3
      dimethylammonio)propylammonio butanoate bromide (2), and 5-(3
      dimethylammonio)propylammonio pentanoate bromide (3) have been obtained in
      reaction of 1,1-dimethyl-1,3-propylenediamine with 3-bromopropionic acid, ethyl 4
      bromobutyrate and 5-bromovaleric acid, respectively. The products have been
      characterized by FTIR, Raman and NMR spectroscopy. Also B3LYP calculations have
      been carried out. The screening constants for 13C and 1H atoms have been
      calculated by the GIAO/B3LYP/6-311G(d,p) approach and analyzed. Theoretical
      vibrational parameters are compared with obtained experimental parameters.
      Estimation of the pharmacotherapeutic potential has been accomplished for the
      synthesized compounds on the basis of Prediction of Activity Spectra for
      Substances (PASSs). 

PMID- 24664326
TI  - Synthesis, characterization and application of various types of alumina and nano
      gamma-alumina sulfuric acid for the synthesis of 2,5-disubstituted 1,3,4
      oxadiazoles.
AB  - An efficient and green protocol for the synthesis of 2,5-disubstituted 1,3,4
      oxadiazoles by one-pot reaction of different aromatic carboxylic acids and
      benzoyl hydrazides using natural alumina, alumina sulfuric acid (ASA), nano-gamma
      alumina and nano-gamma-alumina sulfuric acid (nano-gamma-ASA) under microwave
      irradiation and solvent-free conditions was developed. Short reaction times, mild
      reaction conditions, easy work-up, and high yields are the main advantages of
      this methodology. The catalysts could be recovered and reused for the subsequent
      reactions without any appreciable loss of efficiency. 

PMID- 24664327
TI  - A dinuclear cadmium(II) Schiff base thiocyanato complex: crystal structure and
      fluorescence.
AB  - A new dinuclear cadmium(II) complex, [Cd(L)(NCS)]2 (1) has been synthesized using
      a potentially tetradentate Schiff base ligand HL, 2-((E)-(2
      (diethylamino)ethylimino)methyl)-6-methoxyphenol, obtained by the condensation of
      2-diethylaminoethylamine and o-vanillin, and characterized by different
      physicochemical techniques. Crystal structure of the title complex was
      unambiguously established by single crystal X-ray diffraction which reveals that
      metal centers are connected by bridging phenolato and chelating methoxy oxygen
      atoms of the coordinating Schiff bases and embedded in severely distorted
      octahedral geometries. Fluorescence properties of the ligand and its complex,
      studied at room temperature indicate that later may serve as strong fluorescent
      emitter. 

PMID- 24664328
TI  - Calcium trifluoroacetate as an efficient catalyst for ring-opening of epoxides by
      amines under solvent-free conditions.
AB  - Ca(CF3CO2)2 efficiently catalyzed the selective ring-opening of epoxides by
      amines leading to the synthesis of beta-aminoalcohols. The reaction works well
      with various aromatic and aliphatic amines under solvent-free conditions.
      Corresponding beta-aminoalcohols were obtained in excellent yields with high
      regioselectivity. The catalyst was easily prepared by reaction of CaH2 in
      trifluoroacetic acid. 

PMID- 24664329
TI  - Thiol reactive probe based on fluorescence resonance energy transfer between
      fluorescein and Au nanoparticles.
AB  - Sensitive and selective fluorescent probe of thiols with lower limit of detection
      based on fluorescence resonance energy transfer (FRET) between fluorescein and Au
      nanoparticles (AuNPs) is presented. The fluorescein-AuNPs complex emits weak
      fluorescence. Upon chemically binding to organosulfur compound that contains a
      carbon-bonded sulfhydryl (-C-SH or R-SH) thiols, a stable enhancement of
      fluorescence is observed due to the competitive binding on AuNPs between thiols
      and fluorescein. The magnitude of fluorescence enhancement is linearly
      proportional to the logarithm of the thiols concentration. We use cysteine as an
      example to show how this useful analytical assay works selectively, which is
      closely nonresponsive to 20 other amino acids even though they are in solution at
      a concentration 10 times greater than the thiols. The detection limit for
      cysteine is 7.27 * 10-9 mol L-1. The possible mechanism of this assay is
      discussed in details. The proposed method was successfully applied for the
      determination of Cys in urine. 

PMID- 24664330
TI  - Optical analysis of hafnium oxide-aluminum multilayer structures for transparent
      heat mirrors.
AB  - We report on HfO2/Al/HfO2 multilayer thin films for heat mirror applications
      prepared on corning glass substrates by electron beam evaporation. Films
      fabricated at a substrate temperature of 100  degrees C show nano-polycrystals of
      HfO2 embedded in a disordered lattice according to X-ray diffraction results.
      Atomic force microscopy revealed that HfO2/Al/HfO2 layers possess smooth surface
      that is appropriate for optical heat mirror applications. Study of optical
      properties by UV-Visible spectrophotometer demonstrated that transmittance of
      HfO2/Al/HfO2 device was decreasing from UV to VIS and then slightly increasing in
      the NIR regions, with an opposite trend followed by reflectance. Optical
      constants i.e. refractive index, extinction coefficient, band gap energy, Urbach
      energy has also been calculated. The optical band gap and Urbach energy are found
      to be 4.34 eV and 3.164 eV, respectively. The collective oscillation energy loss
      for heat mirrors applications are also observed. 

PMID- 24664332
TI  - Silica tungstic acid as an efficient and reusable catalyst for the one-pot
      synthesis of 2-amino-4H-chromene derivatives.
AB  - Silica tungstic acid (STA) has been found to be an efficient and reusable solid
      acid catalyst for the synthesis of 2-amino-4H-chromenes via the three-component
      reaction of aromatic aldehydes, malononitrile, and beta-naphthol. STA as a novel
      solid acid was characterized by X-ray fluorescence, X-ray diffraction, and
      Fourier transform infrared spectroscopy. 

PMID- 24664331
TI  - EHPG iron(III) complexes as potential contrast contrast agents for MRI.
AB  - A series of EHPG ligands and complexes were obtained. The derivatives of choice
      were p-OMe, 3,4-dimethyl, p-NHAc and p-Ph substituted ones. The complexes were
      characterized by NMR relaxation decay (T1), EPR and cyclic voltammetry (CV). r1
      Relaxivity of the Fe-EHPG-OMe, Fe-EHPG-Ph derivatives was found higher than that
      of Fe-EHPG. EPR measurements at liquid nitrogen temperature indicate a typical
      rhombohedral structure for both rac- and meso-diastereoisomers of the EHPG
      complexes. CV revealed the redox inactivity of the Fe-EHPG complexes at
      physiological conditions. Interpretation and discussion of the results is
      presented. 

PMID- 24664333
TI  - Calu-3 model under AIC and LCC conditions and application for protein
      permeability studies.
AB  - Broad area of respiratory epithelium with mild surface conditions is an
      attractive possibility when trans-mucosal delivery of protein drugs is
      considered. A mucus and cellular barrier of respiratory epithelium can be
      modelled in vitro by Calu-3 cell line. We have monitored morphology and barrier
      properties of Calu-3 culture on permeable supports while developing into liquid
      covered or air interfaced and mucus lined cellular barrier. Besides morphological
      differences, cultures differed in electrical resistance and permeability to
      proteins as well. The accelerated permeability to proteins in these models, due
      to permeability modulator MP C16, was examined. The effect on electrical
      resistance of cellular layer was rapid in both cultures suggesting easy access of
      MP C16 to cells even though its overall impact on cell permeability was strongly
      reduced in mucus covered culture. Differences in properties of the two models
      enable better understanding of protein transmucosal permeability, suggesting
      route of transport and MP C16 modulator action. 

PMID- 24664334
TI  - Simultaneous determination of phthalates, their metabolites, alkylphenols and
      bisphenol A using GC-MS in urine of men with fertility problems.
AB  - A GC-MS method was successfully applied to measure simultaneously the
      concentrations of endocrine disrupting compounds (5 dialkyl phthalates, 9
      phthalate monoesters, 3 alkylphenols and bisphenol A) in 136 male urine samples.
      In the present study the method was validated and concentrations of EDCs were
      determined. The results were compared with results from other studies.
      Correlations between endocrine disrupting compounds and also correlations of
      endocrine disrupting compounds with two semen quality parameters are presented
      and evaluated. Significant positive correlations were found between almost all
      the endocrine disrupting compounds. The parameter sum of DEHP (SUM DEHP) was
      positively correlated to all the endocrine disrupting compounds but negatively to
      two semen quality parameters. Negative correlations between the endocrine
      disrupting compounds and the semen quality parameters could indicate that
      endocrine disrupting compounds could cause reproductive problems by decreasing
      the semen count and quality. This research will have helped to evaluate human
      exposure to endocrine disrupting compounds. 

PMID- 24664335
TI  - Synthesis, crystal structure and spectroscopic studies of copper complexes with
      tridentate Schiff base ligand.
AB  - Four Cu(II) complexes [CuLX], where X = NO3 (1), Br (2), Cl (3), ClO4 (4) and L =
      benzoylacetonacetohydrazid tridentate Schiff base, HL, have been synthesized and
      characterized by elemental analysis, FT-IR, UV-Vis spectroscopy. The structure of
      compound 1, has been determined by single-crystal X-ray diffraction analysis. The
      structure of 1 is a mononuclear species, the coordination geometry around the
      copper(II) ion is four coordinated square planar, L acts as a tridentate ligand
      which forms one five-membered and one six-membered chelate rings with the Cu(II)
      metal center, and the fourth position at the Cu ion is occupied by the NO3 anion.
      The nitrate ions play role in the H bonding network. In fact the amide NH groups
      act as H donor towards the nitrate oxygen. The formation of the copper complexes
      in solution was monitored by a UV/Vis titration experiment. The results revealed
      that the complexes were of the composition (ligand/metal) 1:1 in solution. 

PMID- 24664336
TI  - Synthesis, characterization, cytotoxicity and DNA binding studies of a nNovel
      anionic organopalladium(II) complex.
AB  - A new anionic 8-hydroxyquinolinatopalladate(II) complex with malonate has been
      synthesized and characterized by elemental analysis, conductivity, FT-IR, UV-Vis
      and 1H NMR techniques to enhance the development of potential anticancer agents.
      Cytotoxicity was determined against the human leukemia cells, molt, by MTT assay.
      The novel antitumor Pd(II) complex was evaluated for its binding to calf thymus
      DNA (ctDNA) in physiological buffer (pH 7.0) by using absorption spectroscopy,
      fluorescence titration spectra, ethidium bromide displacement and gel
      chromatography studies. The results obtained from these analyses indicated that
      the water-soluble complex can bind to DNA cooperatively through a static
      quenching procedure at low concentrations. Thermodynamic parameters obtained from
      fluorescence experiments at different temperatures revealed the hydrogen binding
      and van der Waals force in the binding process which was supported by Scatchard's
      plots. 

PMID- 24664337
TI  - Spectroscopic, potentiometric and quantum-mechanical studies of S-(-)-nicotine
      complexes with Cu(II) ion.
AB  - Copper(II)-nicotine complexes with chelating perchlorate, nitrate, acetate and
      formate ligands have been synthesized and characterized in solid state by
      elemental analysis and FT-IR spectroscopy. Coordination of Cu(II) by nicotine
      molecule has been also studied in water solution of various pH by potentiometry
      and spectroscopic (VIS, EPR and NMR) methods. Furthermore, quantum-mechanical
      calculations helped elucidate the experimental data as they provided some
      information on the energetic of the possible interaction modes of Cu(II) with
      nicotine. The studies showed that nicotine acts as a monodentate ligand utilizing
      for this purpose the pyridine nitrogen atom. In the Cu(II)/Nicotine system the
      MHL and ML type complexes were formed in 1:1 metal:ligand ratio. 

PMID- 24664338
TI  - Toxicity of magnetic chitosan micro and nanoparticles as carriers for
      biologically active substances.
AB  - Nanoparticles of inorganic magnetic core surrounded by layers of functional
      coatings are potential representatives of nanostructures for immobilization of
      bio-substances. Magnetic nanoparticles (MNPs) are often bound in aggregates due
      to a strong magnetic dipole, which has a lot of advantages, such as large surface
      area for binding biologically active substances. Chitosan is a polysaccharide
      polymer that is non-toxic, hydrophilic, biocompatible and has hydroxy and amino
      groups in its structure. Because of these chemical and biological properties it
      is a desirable bio-product for immobilization of enzymes and for binding of other
      biologically active substances. Magnetic micro and nanoparticles were synthesized
      with chitosan by three different methods; microemulsion process, suspension cross
      linking technique and covalent binding of chitosan. Toxic effect of the prepared
      magnetic particles was determined as well and was examined on five different
      bacterial cultures; Escherichia coli, Staphylococcus aureus, Pseudomonas
      aeruginosa, Enterococcus faecalis and Klebsiella pneumoniae. At concentrations of
      10-30 mg of magnetic particles per 0.5 McFarland Standard solution of E. coli and
      per 400 CFU of S. aureus, P. aeruginosa, E. faecalis in K. pneumonia, no
      inhibition on the chosen bacterial cultures was detected. 

PMID- 24664339
TI  - Kinetics and mechanism of ligand exchange reaction of copper(II) complexes with
      tetradentate Schiff base ligands.
AB  - The kinetics of a ligand exchange in the CuL4/H2Ln system, where H2Ln is the N,N'
      alkylen-bis(salicyldimine) tetradentate Schiff base ligand (n = 2 or 3, CH2
      groups in the chain length of the amine backbone) was studied
      spectrophotometrically in DMF solvent with or without triethylamine (NEt3) and
      H2O at 25 +/- 0.1  degrees C and an ionic strength of 0.01 M NaNO3. The reaction
      rate was found to be first-order with respect to CuL4 complex and H2Ln ligand.
      The rate of the ligand exchange reaction did not change significantly with the
      addition of H2O to the DMF solvent; however, it increased when NEt3 was added to
      the reaction mixture. The effect of NEt3 and H2O on the ligand exchange rate
      shows that the deprotonation/protonation of the H2Ln ligand and anionic form of
      H2Ln are essential to the reaction. A reaction mechanism is proposed and
      discussed for the effect of NEt3 and H2O on the ligand exchange rate. 

PMID- 24664340
TI  - Condensation reaction between carbohydrazide and salicylaldehyde: in-line
      vibrational spectroscopy monitoring and characterization of the reaction products
      in solution and solid state.
AB  - The condensation reaction between carbohydrazide and salicylaldehyde was
      monitored in-line by using vibrational NIR and Raman spectroscopies and
      statistical methods. Prior to in-line data analysis the reaction products were
      fully characterized in solution and solid state in order to check the potential
      of the in-line approach as a tool for in-process Schiff bases reaction control.
      It was demonstrated that a combination of vibrational spectroscopy and principal
      component analysis made it possible to detect and identify the reaction products,
      e.g. mono(salicylidene)carbohydrazide (1) and bis(salicylidene)carbohydrazide (2)
      in different solvents, and to determine the reaction end points in real time.
      Owing to complexity of the reaction mixtures and band overlapping, it was not
      possible to determine the relative ratio of the reaction products in-line. The
      off-line analysis showed that 1 was predominant in methanol while the highest
      portion of 2 was obtained in ethanol. 

PMID- 24664341
TI  - Synthesis, crystal structures, and antibacterial evaluation of metal complexes
      based on functionalized 2-phenylquinoline derivatives.
AB  - A series of dinuclear paddle-wheel like transition metal complexes based on 2
      phenylquinoline-4-carboxylic derivative L have been synthesized and characterized
      by IR, elemental analysis, and X-ray diffraction single crystal analysis. The
      biological activities of L and its complexes were evaluated as assayed
      antibacterial activities, including Escherichia coli, Pseudomonas aeruginosa,
      Bacillus subtilis and Staphylococcus aureus. The results indicated that these
      complexes showed better antibacterial activities than the free ligand or metal
      salts alone. Among them, the Zn(II) and Cd(II) complexes with IC50 of 0.57 ug/mL
      and 0.51 ug/mL, respectively, showed excellent antibacterial activity against
      Staphylococcus aureus. 

PMID- 24664342
TI  - Nano scale magnetically recoverable supported heteropoly acid as an efficient
      catalyst for the synthesis of benzimidazole derivatives in water.
AB  - 12-Tungstophosphoric acid supported on silica-coated magnetic nano particles was
      prepared and characterized by transmission electron microscopy, scanning electron
      microscopy, powder X-ray diffraction and inductively coupled plasma atomic
      emission spectroscopy. Acidity of the catalysts was measured by potentiometric
      titration with n-butylamine. Catalytic activity of the prepared sample was
      evaluated in the model synthesis of 1,2-disubstituted benzimidazole derivatives
      in water. The catalyst showed excellent catalytic activity and the corresponding
      products were obtained in good to excellent yields under mild reaction
      conditions. Furthermore, the catalyst could be easily recovered using an external
      magnet and reused several times. The leaching and surface acidity of the
      recovered catalyst were also investigated. 

PMID- 24664343
TI  - Efficient synthesis of benzopyrans and dihydropyranochromenes catalyzed by poly(4
      vinylpyridine) as a green and commercially available basic catalyst.
AB  - Poly(4-vinylpyridine) is used as a green, commercially available and recyclable
      basic catalyst for the multicomponent synthesis of benzopyrans and
      dihydropyranochromenes by one-pot condensation of aromatic aldehydes, 3-methyl-1
      phenyl-2-pyrazolin-5-one, and malononitrile or 4-hydroxycoumarin in ethanol at
      reflux temperature. This procedure provides several advantages such as mild
      reaction conditions, short reaction times, simple work-up and high yields. 

PMID- 24664344
TI  - Preconcentration and trace determination of cadmium in spinach and various water
      samples by temperature-controlled ionic liquid dispersive liquid phase
      microextraction.
AB  - A sensitive and selective method for the preconcentration and separation of sub
      ug L-1 levels of cadmium ions in aqueous solutions with high salt contents is
      described. The developed method is based on temperature-controlled ionic liquid
      dispersive liquid phase microextraction of cadmium using the 1-hexyl-3
      methylimidazolium bis (trifluoromethylsulfonyl) imide (ionic liquid (IL)) as an
      extractant followed by flame atomic absorption spectrometry determination. The
      extraction of cadmium ions from the aqueous solution into the fine droplets of IL
      was performed with dithizone as the chelating agent. Some predominant factors
      affecting the preconcentration of cadmium ions were evaluated and optimized.
      Under the optimum conditions, the calibration graph was linear over the
      concentration range from 0.6-20.0 ug L-1 of cadmium and the limit of detection
      (LOD) was 0.2 ug L-1. The enrichment factor was found to be 25. The developed
      method was successfully applied to the determination of cadmium in spinach and
      water samples. 

PMID- 24664345
TI  - Al2O3 nanoparticles: an efficient and recyclable nanocatalyst for the rapid
      synthesis of N-heteroaryl formamides under solvent-free conditions.
AB  - A series of N-heteroaryl formamides were efficiently synthesized from
      heteroarylamines and formic acid using Al2O3 nanoparticles as a heterogeneous
      catalyst under solvent-free conditions. The smaller size of Al2O3 nanoparticles
      with a higher surface to volume ratio has a promising catalytic activity,
      resulting in a short reaction times and high reaction yields under mild reaction
      conditions. The catalyst could be recycled and reused four times without a
      noticeable decrease in its activity. 

PMID- 24664346
TI  - Simultaneous determination of nitrophenols and poly-aromatic hydrocarbons in
      aquatic samples by solid phase extraction and HPLC analysis.
AB  - A method for the simultaneous extraction and HPLC analysis of nitrophenols and
      poly-aromatic hydrocarbons (PAHs) in aquatic samples is presented. The efficiency
      of the solvent extraction and the solid phase extraction (SPE) is compared. The
      results showed that the polymeric SPE sorbent is the best compromise for the
      simultaneous extraction of the tested compounds taking into consideration the
      lipophilicity of PAHs and the polarity of nitrophenols. The best results were
      obtained on polymeric Strata X sorbent, elution with dichloromethane followed by
      elution with methanol. Silica gel C18 sorbent is improper for nitrophenols due to
      the strong interactions with the residual hydroxyl groups of silica gel. The
      developed SPE-HPLC method was successfully applied for the analysis of these
      pollutants in different water samples. 

PMID- 24664347
TI  - Nanocomposite foams from iron oxide stabilized dicyclopentadiene high internal
      phase emulsions: preparation and bromination.
AB  - Nanocomposite polyHIPE foams with open-cellular morphology were obtained using
      nanoparticles (gammaFe2O3/Fe3O4), surfactant (Pluronic L121) or
      nanoparticle/surfactant stabilized dicyclopentadiene high internal phase
      emulsions (DCPD HIPEs). Upon curing, cavity sizes were found to vary drastically
      between 950 +/- 360 um down to 7 +/-3 um depending on the HIPE formulations. As
      obtained nanocomposite polyHIPE foams were functionalized using elemental bromine
      in THF. Upon bromination the nanoparticles are moved from the cavities surfaces
      into the bulk phase of the polymer scaffold, which affects the inductive-heating
      capability of the magnetic nanocomposite foams decreasing it by the factor of 2. 

PMID- 24664349
TI  - Gastrointestinal tolerance and utilization of agave inulin by healthy adults.
AB  - Little clinical research exists on agave inulin as a fiber source. Due to
      differences in botanical origin and chemical structure compared to other inulin
      type fibers, research is needed to assess gastrointestinal (GI) tolerance
      following consumption. This study aimed to evaluate GI tolerance and utilization
      of 5.0 and 7.5 g per day of agave inulin in healthy adults (n = 29) using a
      randomized, double-blind, placebo-controlled crossover trial consisting of three
      21 day periods with 1 week washouts among periods. GI tolerance was assessed via
      daily and weekly questionnaires, three fecal samples were collected on days 16-20
      of each period, and breath hydrogen testing was completed on the final day of
      each treatment period. Survey data were compared using a generalized linear mixed
      model. All other outcomes were analyzed using a mixed linear model with a
      repeated measures procedure. Composite GI intolerance scores for 5.0 and 7.5 g
      treatments were both greater (P < 0.05) than control, however, scores were low,
      with means of 0.4, 1.9, and 2.3 on a 0-12 point composite scale for 0, 5.0, and
      7.5 g treatments, respectively. There were slight increases (P < 0.05) in
      bloating, flatulence, and rumbling frequency with 5.0 and 7.5 g agave inulin.
      Abdominal pain and rumbling intensity were marginally greater (P < 0.05) with 7.5
      g. Bloating and flatulence intensity increased (P < 0.05) with 5.0 g and 7.5 g.
      Agave inulin did not affect diarrhea (P > 0.05). Number of bowel movements per
      day increased, stools were softer, and stool dry matter percentage was lower with
      7.5 g (P < 0.05). Breath hydrogen concentrations increased (P < 0.001) from 5-8
      hour postprandial when participants consumed agave inulin compared to control.
      These data demonstrate that doses up to 7.5 g per day of agave inulin led to
      minimal GI upset, do not increase diarrhea, and improve laxation in healthy young
      adults. 

PMID- 24664350
TI  - Assessment of the biological pathways targeted by isocyanate using N-succinimidyl
      N-methylcarbamate in budding yeast Saccharomyces cerevisiae.
AB  - Isocyanates, a group of low molecular weight aromatic and aliphatic compounds
      possesses the functional isocyanate group. They are highly toxic in nature hence;
      we used N-succinimidyl N-methylcarbamate (NSNM), a surrogate chemical containing
      a functional isocyanate group to understand the mode of action of this class of
      compounds. We employed budding yeast Saccharomyces cerevisiae as a model organism
      to study the pathways targeted by NSNM. Our screening with yeast mutants revealed
      that it affects chromatin, DNA damage response, protein-ubiquitylation and
      chaperones, oxidative stress, TOR pathway and DNA repair processes. We also show
      that NSNM acts as an epigenetic modifier as its treatment causes reduction in
      global histone acetylation and formation of histone adducts. Cells treated with
      NSNM exhibited increase in mitochondrial membrane potential as well as
      intracellular ROS levels and the effects were rescued by addition of reduced
      glutathione to the medium. We also report that deletion of SOD1 and SOD2, the
      superoxide dismutase in Saccharomyces cerevisiae displayed hypersensitivity to
      NSNM. Furthermore, NSNM treatment causes rapid depletion of total glutathione and
      reduced glutathione. We also demonstrated that NSNM induces degradation of Sml1,
      a ribonucleotide reductase inhibitor involved in regulating dNTPs production. In
      summary, we define the various biological pathways targeted by isocyanates. 

PMID- 24664351
TI  - Increased depression, diabetes and diabetic complications in Graves' disease
      patients in Asia.
AB  - BACKGROUND: This study aimed to evaluate the risk of depression and other
      cardiovascular comorbidities in Graves' disease (GD) patients in Asia. METHODS:
      The study patients were all newly diagnosed with GD [International Classification
      of Disease, 9th Revision, Clinical Modification (ICD-9-CM) 242.0] from January
      1998 to December 2008. Patients aged <20 years or those with preexisting mental
      disorder (ICD-9-CM 290-319) were excluded from analyses. Control patients were
      randomly selected for the non-GD cohort, 1:4 frequency matched to the GD cohort
      according to sex, age and index year. The same exclusion criteria applied to the
      GD cohort were applied to the non-GD cohort. The GD cohort contained 4195
      patients and the non-GD cohort contained 16 780 patients. RESULTS: The GD
      patients were more likely to have diabetes (8.03% vs. 4.48%, P < 0.0001),
      hypertension (18.1% vs. 13.5%, P < 0.0001), hyperlipidemia (11.9% vs. 9.09%, P <
      0.0001) and coronary artery disease (10.3% vs. 5.86%, P < 0.0001) than the
      control patients were. The GD patients were also associated with significantly
      higher risk of depression than the control patients were (hazard ratio = 1.69,
      95% confidence interval = 1.45-1.96). CONCLUSION: GD and GD treatment are
      associated with increased risk of depression diabetes and diabetic complications
      in Asian patients.

PMID- 24664354
TI  - Selective isolation of the electron or hole in photocatalysis: ZnO-TiO2 and TiO2
      ZnO core-shell structured heterojunction nanofibers via electrospinning and
      atomic layer deposition.
AB  - Heterojunctions are a well-studied material combination in photocatalysis
      studies, the majority of which aim to improve the efficacy of the catalysts.
      Developing novel catalysts begs the question of which photo-generated charge
      carrier is more efficient in the process of catalysis and the associated
      mechanism. To address this issue we have fabricated core-shell heterojunction
      (CSHJ) nanofibers from ZnO and TiO2 in two combinations where only the 'shell'
      part of the heterojunction is exposed to the environment to participate in the
      photocatalysis. Core and shell structures were fabricated via electrospinning and
      atomic layer deposition, respectively which were then subjected to calcination.
      These CSHJs were characterized and studied for photocatalytic activity (PCA).
      These two combinations expose electrons or holes selectively to the environment.
      Under suitable illumination of the ZnO-TiO2 CSHJ, e/h pairs are created mainly in
      TiO2 and the electrons take part in catalysis (i.e. reduce the organic dye) at
      the conduction band or oxygen vacancy sites of the 'shell', while holes migrate
      to the core of the structure. Conversely, holes take part in catalysis and
      electrons diffuse to the core in the case of a TiO2-ZnO CSHJ. The results further
      revealed that the TiO2-ZnO CSHJ shows ~1.6 times faster PCA when compared to the
      ZnO-TiO2 CSHJ because of efficient hole capture by oxygen vacancies, and the
      lower mobility of holes. 

PMID- 24664355
TI  - Chlorhexidine-based oral care and ventilator-associated pneumonia: the devil in
      disguise?

PMID- 24664352
TI  - The neurobiology of cancer pain.
AB  - The global burden of cancer pain is enormous and opioids, despite their side
      effects, remain the primary therapeutic approach. The cause of cancer pain is
      unknown. Mechanisms driving cancer pain differ from those mechanisms responsible
      for inflammatory and neuropathic pain. The prevailing hypothesis put forward to
      explain cancer pain posits that cancers generate and secrete mediators which
      sensitize and activate primary afferent nociceptors in the cancer
      microenvironment. Moreover, cancers induce neurochemical reorganization of the
      spinal cord, which contributes to spontaneous activity and enhanced
      responsiveness. The purpose of this review, which covers clinical and preclinical
      studies, is to highlight those peripheral and central mechanisms responsible for
      cancer pain. The challenges facing neuroscientists and clinicians studying and
      ultimately treating cancer pain are discussed. 

PMID- 24664357
TI  - Inappropriate referrals at the end of life--the existing Indian scenario.
AB  - The Economist Intelligence Unit has ranked India's end-of-life care last out of
      40 countries. The lack of orientation towards palliative care, poor communication
      skills, a disease-focused, curative approach and the unending battle against
      death-all lead to unrealistic hope in patients and their families. Inappropriate
      referrals at the end of life are common and result in a lot of avoidable
      suffering for both the patients and their families. Propagation of clear
      guidelines to limit inappropriate therapeutic interventions and referrals in
      patients with limited prognosis is the need of the hour. Awareness,
      sensitization, education and training in palliative care are urgently required to
      change attitudes. This would go a long way in mitigating the misery for both the
      dying and their carers. 

PMID- 24664356
TI  - Item response theory analysis of the patient satisfaction with cancer-related
      care measure: a psychometric investigation in a multicultural sample of 1,296
      participants.
AB  - BACKGROUND: We developed and validated a Patient Satisfaction with Cancer-Related
      Care (PSCC) measure using classical test theory methods. The present study
      applied item response theory (IRT) analysis to determine item-level psychometric
      properties, facilitate development of short forms, and inform future applications
      for the PSCC. METHODS: We applied unidimensional IRT models to PSCC data from
      1,296 participants (73% female; 18 to 86 years). An unconstrained graded response
      model (GRM) and a Rasch Model were fitted to estimate indices for model
      comparison using likelihood ratio (LR) test and information criteria. We computed
      item and latent trait parameter estimates, category and operating characteristic
      curves, and tested information curves for the better fitting model. RESULTS: The
      GRM fitted the data better than the Rasch Model (LR = 828, df = 17, p < 0.001).
      The log-likelihood (-17,390.38 vs. -17,804.26) was larger, and the AIC and BIC
      were smaller for the GRM compared to the Rash Model (AIC = 34,960.77 vs.
      35,754.73; BIC = 35,425.80 vs. 36,131.92). Item parameter estimates (IPEs) showed
      substantial variation in items' discriminating power (0.94 to 2.18). Standard
      errors of the IPEs were small (threshold parameters mostly around 0.1;
      discrimination parameters 0.1 to 0.2), confirming the precision of the IPEs.
      CONCLUSION: The GRM provides precise IPEs that will enable comparable scores from
      different subsets of items, and facilitate optimal selections of items to
      estimate patients' latent satisfaction level. Given the large calibration sample,
      the IPEs can be used in settings with limited resources (e.g., smaller samples)
      to estimate patients' satisfaction.

PMID- 24664358
TI  - Positive changes following cancer: posttraumatic growth in the context of other
      factors in patients with cancer.
AB  - PURPOSE: The incidence of posttraumatic growth (PTG) has mostly been researched
      after typical traumatic events such as war, violence, bereavement, vehicle
      accidents, and so forth. This research has shown that PTG also occurs after
      cancer. This article presents the results of research which focused on PTG and
      what was related to its incidence, such as the specific reaction to trauma, among
      patients with hematological cancer (N = 72). The differences in the levels of PTG
      were analyzed from the perspective of demographic characteristics,
      characteristics of the disease, and treatment. METHODS: PTG was measured using
      the Posttraumatic Growth Inventory-Czech version (PTGI-CZ). The associated
      variables were measured using instruments in measuring benefit findings [Benefit
      Finding Scale for Children-Czech version (BFSC-CZ)], distress tolerance [Distress
      Tolerance Scale (DTS)], hope [Adult Hope Trait Scale (AHTS)], and optimism
      [Revised Life Orientation Test (LOT-R)]. RESULTS: Regression analysis found that
      a higher perception of benefits of the disease (benefit findings) and a greater
      effort to regulate feelings of distress (distress regulation) explained 67.1% of
      the variance of PTG. CONCLUSIONS: There were no significant differences in the
      level of PTG in terms of demographic indicators, type of cancer, current state of
      disease, or type of treatment. It was found that it was important for patients to
      perceive that their disease had been beneficial in a certain way. It was also
      important that patients made a great effort to regulate distress, which can occur
      when coping with the negative consequences of a disease, and at the same time, it
      is important for the process of PTG.

PMID- 24664359
TI  - Vitamin D deficiency in patients with malignancy in Brisbane.
AB  - PURPOSE: This study aims to investigate the prevalence and factors predictive of
      vitamin D deficiency in patients with malignancy in Brisbane, Australia (latitude
      27 degrees  S). METHODS: This is a prospective cross-sectional study measuring
      serum levels of 25-hydroxyvitamin D (25-OHD) in 100 subjects with non
      haematological cancer at least 18 years of age not taking vitamin D supplements
      attending a day oncology unit and oncology/palliative care inpatient ward in
      Brisbane, Australia. RESULTS: Thirty-seven per cent of outpatient and 49 % of
      inpatient subjects respectively were vitamin D deficient. Functional status was
      predictive of low vitamin D levels. CONCLUSION: There was a high prevalence of
      vitamin D deficiency in patients with cancer in Brisbane, Australia.

PMID- 24664360
TI  - Association between serum levels of adiponectin and polychlorinated biphenyls in
      Korean men and women.
AB  - Persistent organic pollutants (POPs) are endocrine-disrupting chemicals
      associated with metabolic syndrome and type 2 diabetes. In humans, little is
      known about their potential role on obesity. Adiponectin augments the effects of
      insulin on glucose homeostasis. The expression of adiponectin is reduced in
      obesity, insulin resistance, and type 2 diabetes. The aim of this study is to
      reveal whether accumulation of the POPs, especially polychlorinated biphenyls
      (PCBs), is associated with serum levels of adiponectin in Koreans. This cross
      sectional study includes 98 Koreans (49 men and 49 women). Serum levels of marker
      PCBs (PCB 28, 52, 101, 138, 153, and 180) were measured by Agilent 7890GC-micro
      ECD (Gas chromatography-micro-electron capture detector). Total adiponectin
      levels were quantified by enzyme-linked immunosorbent assay. We defined high
      (>=Median) and low (<Median) body mass index (BMI) groups by using median value
      of BMI (24.6 kg/m2 for men; 23.0 kg/m2 for women). PCB28, PCB138, and PCB153 were
      significantly negatively associated with adiponectin levels (beta-coefficients=
      0.00741 for PCB28; -0.00438 for PCB138; -0.00406 for PCB153). When we divided
      subjects by sex, PCB28 and PCB153 were inversely associated with adiponectin in
      women. In the high BMI group (>=Median), PCB153 showed the significant negative
      associations with adiponectin levels (P<0.05). However, these associations were
      not seen in the low BMI group. In conclusion, we found negative associations
      between PCBs and adiponectin. This cross-sectional study could provide support
      for the hypothesis that POPs exposure might contribute to type 2 diabetes as well
      as obesity.

PMID- 24664361
TI  - Perception of health and cognitive dysfunction in acromegaly patients.

PMID- 24664362
TI  - The peculiar ultrasonographic and elastographic features of thyroid nodules after
      treatment with laser or radiofrequency: similarities and differences.
AB  - The aim of percutaneous thermal ablation with laser (LA) or radiofrequency (RFA)
      is to reduce the volume of benign thyroid nodules. Little is known about
      ultrasonographic and elastographic appearances of thyroid lesions after
      treatment. For the first time, we report in detail the main ultrasonographic and
      elastographic characteristics of thermally ablated nodules and their underlying
      similarities and differences. Both thermal treatments usually produce a marked
      hypoechoic area of coagulative necrosis. LA-treated lesions usually become highly
      heterogeneous due to the presence of cavitations and charring; they then evolve
      into hyperechoic scars. In RFA-treated nodules, instead, the necrotic area is
      more homogeneous but presents more irregular margins compared to those observed
      in LA-treated lesions. Regardless of the thermal method used, vascularity is
      typically reduced in all treated nodules and stiffness, evaluated with
      qualitative elastography, increases. In conclusion, ultrasonographic and
      elastographic appearances of the thermally ablated thyroid lesions differ
      slightly according to the adopted procedure. Furthermore, they are peculiar,
      changeable over time, and potentially misleading.

PMID- 24664363
TI  - The styloid process in a Greek population: an anatomical study with clinical
      implications.
AB  - The study determines the variability of the length of the styloid process in a
      Greek population and investigates how it is affected by gender and age; it also
      evaluates the side asymmetry, highlighting clinical implications. One hundred and
      forty-nine dry adult modern skulls (94 male and 55 female) were divided into
      subgroups according to their age: 20-39, 40-59 and older than 60 years. The
      lengths of 262 styloid processes (127 right and 135 left-sided) were measured.
      The lengths of right-sided styloid processes ranged from 6.4 to 70.2 mm and left
      sided styloid processes from 5.2 to 69.0 mm. The processes were classified
      according to their lengths as short <18 mm, normal 18-33 mm and elongated >33 mm.
      The majority of the processes were normal (45.8 %), 27.5 % were short and 26.7 %
      elongated. No statistical significant correlation was established among the
      lengths of the styloid processes, gender and age. Side asymmetry was found only
      in the group with elongated styloid processes (right processes were longer, 28.3
      %, than the left ones 25.2 %; p = 0.016). Our study contributes to the
      literature, adding important information about the length of the styloid process
      and its diversity in the Greek population. It also confirms the existence of an
      osseous landmark as a starting point for the measurement of the length of the
      styloid process and proposes a method of measurement for the evaluation of the
      actual length of the styloid process.

PMID- 24664364
TI  - When should we consider renal biopsy in children with isolated microscopic
      hematuria?

PMID- 24664365
TI  - Persistent urinary podocyte loss following preeclampsia may reflect subclinical
      renal injury.
AB  - OBJECTIVE: Studies have shown that podocyturia, i.e., urinary loss of viable
      podocytes (glomerular epithelial cells), is associated with proteinuria in
      preeclampsia. We postulated that urinary podocyte loss may persist after
      preeclamptic pregnancies, thus resulting in renal injury. This may lead to future
      chronic renal injury. In addition, we compared the postpartum levels of the
      angiogenic factors, which previously have been associated with preeclampsia,
      between normotensive versus preeclamptic pregnancies. STUDY DESIGN: The diagnosis
      of preeclampsia was confirmed using standard clinical criteria. Random blood and
      urine samples were obtained within 24 hours prior to delivery and 5 to 8 weeks
      postpartum. Urine sediments were cultured for 24 hours to select for viable cells
      and staining for podocin was used to identify podocytes. Serum samples were
      analyzed for the levels of angiogenic markers using ELISA (enzyme-linked
      immunosorbent assay) methodology. RESULTS: At delivery, preeclamptic patients (n
      = 10) had significantly higher proteinuria (p = 0.006) and podocyturia (p<0.001)
      than normotensive pregnant patients (n = 18). Postpartum proteinuria was similar
      between these two groups (p = 0.37), while podocyturia was present in 3 of 10
      women with preeclampsia and in none of the normotensive controls (p = 0.037).
      Angiogenic marker levels, including placental growth factor, soluble vascular
      endothelial growth factor receptor fms-like tyrosine kinase receptor-1 and
      endoglin, were not significantly different between women with preeclampsia and
      women with a normotensive pregnancy, either at delivery or postpartum.
      CONCLUSION: Persistent urinary podocyte loss after preeclamptic pregnancies may
      constitute a marker of ongoing, subclinical renal injury.

PMID- 24664366
TI  - Trust, deals and authority: community mental health professionals' experiences of
      influencing reluctant patients.
AB  - The emphasis on care in the community in current mental health policy poses
      challenges for community mental health professionals with responsibility for
      patients who do not wish to receive services. Previous studies report that
      professionals employ a range of behaviors to influence reluctant patients. We
      investigated professionals' own conceptualizations of such influencing behaviors
      through focus groups with community teams in England. Participants perceived that
      good, trusting relationships are a prerequisite to the negotiation of reciprocal
      agreements that, in turn, lead to patient-centred care. They described that
      although asserting professional authority sometimes is necessary, it can be a
      potential threat to relationships. Balancing potentially conflicting processes
      one based on reciprocity and the other on authority-represents a challenge in
      clinical practice. By providing descriptive accounts of micro-level dynamics of
      clinical encounters, our analysis shows how the authoritative aspect of the
      professional role has the potential to undermine therapeutic interactions with
      reluctant patients. We argue that such micro-level analyses are necessary to
      enhance our understanding of how patient-centered mental health policy may be
      implemented through clinical practice. 

PMID- 24664367
TI  - Social inequalities in psychological well-being: a European comparison.
AB  - The objective was to explore the educational differences in psychological well
      being, measured using the WHO-5 Index, among 15,362 men and 20,272 women in 31
      European countries. Relative Index of Inequality, multilevel logistic regression
      analyses and interaction tests were performed. Within Europe, large cross
      national differences in the prevalence of poor well-being were observed. In
      almost all countries, the prevalence of poor well-being was higher in low
      educational groups, but the magnitude of these inequalities was much larger in
      some countries than in others. The highest social differences in well-being were
      observed in the European Union candidates countries among both genders. Future
      health promotion programs should consider strategies that target lower
      educational groups. 

PMID- 24664368
TI  - Systemic corticosteroids for acute sinusitis.
AB  - BACKGROUND: Acute sinusitis is the inflammation and swelling of the nasal and
      paranasal mucous membranes and is a common reason for patients to seek primary
      care consultations. The related impairment of daily functioning and quality of
      life is attributable to symptoms such as facial pain and nasal congestion.
      OBJECTIVES: To assess the effects of systemic corticosteroids on clinical
      response rates and to determine adverse effects and relapse rates of systemic
      corticosteroids compared to placebo or standard clinical care in children and
      adults with acute sinusitis. SEARCH METHODS: We searched CENTRAL (2014, Issue 1),
      MEDLINE (1966 to February week 1, 2014) and EMBASE (January 2009 to February
      2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing systemic
      corticosteroids to placebo or standard clinical care for patients with acute
      sinusitis. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed the methodological quality of the trials and extracted data. MAIN
      RESULTS: Five RCTs with a total of 1193 adult participants met our inclusion
      criteria. We judged methodological quality to be moderate in four trials and high
      in one trial. Acute sinusitis was defined clinically in all trials. However, the
      three trials performed in ear, nose and throat (ENT) outpatient clinics also used
      radiological assessment as part of their inclusion criteria. All participants
      were assigned to either oral corticosteroids (prednisone 24 mg to 80 mg daily or
      betamethasone 1 mg daily) or the control treatment (placebo in four trials and
      non-steroidal anti-inflammatory drugs (NSAIDs) in one trial). In four trials
      antibiotics were prescribed in addition to oral corticosteroids or control
      treatment, while one trial investigated the effects of oral corticosteroids as a
      monotherapy.When combining data from the five trials, participants treated with
      oral corticosteroids were more likely to have short-term resolution or
      improvement of symptoms than those receiving the control treatment: at days three
      to seven (risk ratio (RR) 1.3, 95% confidence interval (CI) 1.1 to 1.6; risk
      difference (RD) 17%, 95% CI 6% to 29%) and at days four to 14 (RR 1.2, 95% CI 1.0
      to 1.5; RD 14%, 95% CI 1% to 27%). A sensitivity analysis including the four
      trials with placebo as a control treatment showed similar results but with a
      lesser effect size: at days three to seven (RR 1.2, 95% CI 1.1 to 1.3; RD 11%,
      95% CI 4% to 17%) and days four to 14 (RR 1.1, 95% CI 1.0 to 1.2; RD 8%, 95% CI
      2% to 13%). Statistical heterogeneity was high for many analyses. Subgroup
      analyses revealed that corticosteroid monotherapy had no beneficial effects.
      Furthermore, scenario analysis showed that outcomes missing from the trial
      reports might have introduced attrition bias (a worst-case scenario showed no
      statistically significant beneficial effect of oral corticosteroids). No trial
      reported effects on relapse or recurrence rates. Reported side effects in
      patients treated with oral corticosteroids were mild (nausea, vomiting, gastric
      complaints) and did not significantly differ from those receiving placebo.
      AUTHORS' CONCLUSIONS: Oral corticosteroids as a monotherapy appear to be
      ineffective for adult patients with clinically diagnosed acute sinusitis. Current
      data on the use of oral corticosteroids as an adjunctive therapy to oral
      antibiotics are limited: almost all trials are performed in secondary care
      settings and there is a significant risk of bias. This limited evidence suggests
      that oral corticosteroids in combination with antibiotics may be modestly
      beneficial for short-term relief of symptoms in acute sinusitis, with a number
      needed to treat to benefit of seven for resolution or symptom improvement. A
      large primary care factorial trial is needed to establish whether oral
      corticosteroids offer additional benefits over antibiotics in acute sinusitis.

PMID- 24664369
TI  - Expression of PRMT5 correlates with malignant grade in gliomas and plays a
      pivotal role in tumor growth in vitro.
AB  - Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of omega
      NG,N'G-symmetric dimethylarginine residues on histones as well as other proteins.
      These modifications play an important role in cell differentiation and tumor cell
      growth. However, the role of PRMT5 in human glioma cells has not been
      characterized. In this study, we assessed protein expression profiles of PRMT5 in
      control brain, WHO grade II astrocytomas, anaplastic astrocytomas, and
      glioblastoma multiforme (GBM) by immunohistochemistry. PRMT5 was low in glial
      cells in control brain tissues and low grade astrocytomas. Its expression
      increased in parallel with malignant progression, and was highly expressed in
      GBM. Knockdown of PRMT5 by small hairpin RNA caused alterations of p-ERK1/2 and
      significantly repressed the clonogenic potential and viability of glioma cells.
      These findings indicate that PRMT5 is a marker of malignant progression in glioma
      tumors and plays a pivotal role in tumor growth. 

PMID- 24664370
TI  - Transient cerebral hypoperfusion assisted intraarterial cationic liposome
      delivery to brain tissue.
AB  - Transient cerebral hypoperfusion (TCH) has empirically been used to assist
      intraarterial (IA) drug delivery to brain tumors. Transient (<3 min) reduction of
      cerebral blood flow (CBF) occurs during many neuro- and cardiovascular
      interventions and has recently been used to better target IA drugs to brain
      tumors. In the present experiments, we assessed whether the effectiveness of IA
      delivery of cationic liposomes could be improved by TCH. Cationic liposomes
      composed of 1:1 DOTAP:PC (dioleoyl-trimethylammonium-propane:phosphatidylcholine)
      were administered to three groups of Sprague-Dawley rats. In the first group, we
      tested the effect of blood flow reduction on IA delivery of cationic liposomes.
      In the second group, we compared TCH-assisted IA liposomal delivery versus
      intravenous (IV) administration of the same dose. In the third group, we assessed
      retention of cationic liposomes in brain 4 h after TCH assisted delivery. The
      liposomes contained a near infrared dye, DilC18(7), whose concentration could be
      measured in vivo by diffuse reflectance spectroscopy. IA injections of cationic
      liposomes during TCH increased their delivery approximately fourfold compared to
      injections during normal blood flow. Optical pharmacokinetic measurements
      revealed that relative to IV injections, IA injection of cationic liposomes
      during TCH produced tissue concentrations that were 100-fold greater. The
      cationic liposomes were retained in the brain tissue 4 h after a single IA
      injection. There was no gross impairment of neurological functions in surviving
      animals. Transient reduction in CBF significantly increased IA delivery of
      cationic liposomes in the brain. High concentrations of liposomes could be
      delivered to brain tissue after IA injections with concurrent TCH while none
      could be detected after IV injection. IA-TCH injections were well tolerated and
      cationic liposomes were retained for at least 4 h after IA administration. These
      results should encourage development of cationic liposomal formulations of
      chemotherapeutic drugs and their IA delivery during TCH. 

PMID- 24664371
TI  - Karyopherin a2 and chromosome region maintenance protein 1 expression in
      meningiomas: novel biomarkers for recurrence and malignant progression.
AB  - The karyopherin protein family comprises importins and exportins which are
      nucleocytoplasmic shuttling receptors. Increased levels of karyopherin a2 and
      chromosome region maintenance protein 1 correlate with a higher WHO grade and a
      poorer prognosis in patients with infiltrative astrocytomas. The aim of this
      study was to evaluate representative members of importins and exportins (i.e.
      karyopherin a2 and chromosome region maintenance protein 1) as novel biomarkers
      for meningiomas of WHO grades I-III. We semiquantitatively analyzed nuclear
      expression of karyopherin a2, chromosome region maintenance protein 1 and the
      MIB1 labeling index using immunohistochemistry in 108 primary (44 meningiomas WHO
      grade I, 48 meningiomas WHO grade II, 16 meningiomas WHO grade III) and 13
      recurrent meningiomas. Statistical analysis was performed using standard
      techniques. Karyopherin a2 (p < 0.001) and chromosome region maintenance protein
      1 (p = 0.002) expression correlated significantly with the histological grade.
      Karyopherin a2 expression correlated with proliferative activity as assessed by
      the MIB1 index (p < 0.001). Recurrent tumors expressed significantly higher
      levels of karyopherin a2 (p = 0.045) when compared to primary growths.
      Multivariate analysis of the overall series as well as of patients with atypical
      meningiomas identified higher karyopherin a2 (>= 5 vs. <5%) and chromosome region
      maintenance protein 1 (>= 60 vs. 60%) expression as independent predictors of
      tumor recurrence. Karyopherin a2 and chromosome region maintenance protein 1
      expression may have potential as novel biomarkers for meningiomas.

PMID- 24664373
TI  - Let it go.

PMID- 24664372
TI  - Celastrol blocks interleukin-6 gene expression via downregulation of NF-kappaB in
      prostate carcinoma cells.
AB  - Interleukin-6 (IL-6), a multifunctional cytokine, contributes to proliferation or
      differentiation of prostate carcinoma cells in a highly cell type-specific
      manner. Celastrol (3-hydroxy-24-nor-2oxo-1(10),3,5,7-friedelatetrane-29-oic
      acid), also named as tripterine, is extracted from root of Chinese traditional
      herb Tripterygiumwilfordii Hook f with potent anti-inflammatory and anti-cancer
      activities. In this study, we evaluated the molecular mechanisms of celastrol on
      cell proliferation and IL-6 gene expression in prostate carcinoma cells. 3H
      thymidine incorporation and flow cytometric analysis indicated that celastrol
      treatments arrested the cell cycle at the G0/G1 phase, thus attenuating cell
      proliferation in prostate carcinoma PC-3 cells; moreover, celastrol induced cell
      apoptosis at higher dosage. Knockdown of IL-6 attenuated the anti-proliferative
      effect of celastrol on PC-3 cells. Results from ELISA and 5'-deletion transient
      gene expression assays indicated that celastrol treatment decreased IL-6
      secretion and gene expression, and this effect is dependent on the NF-kappaB
      response element within IL-6 promoter area since mutation of the NF-kappaB
      response element from AAATGTCCCATTTTCCC to AAATGTTACATTTTCCC by site-directed
      mutagenesis abolished the inhibition of celastrol on the IL-6 promoter activity.
      Celastrol also attenuated the activation of PMA and TNFalpha on the gene
      expression and secretion of IL-6 in PC-3 cells. Immunoblot assays revealed that
      celastrol treatment downregulated the expressions of IKKalpha, p50 and p65,
      supporting the 5'-deletion transient gene expression assay result that celastrol
      blocked IL-6 expression through the NF-kappaB pathway in PC-3 cells. For the
      first time, our results concluded that celastrol attenuates PC-3 cell
      proliferation via downregulation of IL-6 gene expression through the NF-kappaB
      dependent pathway. 

PMID- 24664374
TI  - PAIR UP for primary care excellence: perspectives from a primary healthcare
      provider in Singapore.
AB  - Singapore is facing an increasing noncommunicable disease burden due to its
      ageing population. Singapore's primary healthcare services, provided by both
      polyclinic physicians and private general practitioners, are available to the
      public at differential fees for service. The resultant disproportionate patient
      loads lead to dissatisfaction for both healthcare providers and consumers. This
      article describes the 'PAIR UP' approach as a potential endeavour to facilitate
      primary care physicians (PCPs) in public and private sectors to collaborate to
      deliver enhanced primary care in Singapore. PAIR UP is an acronym referring to
      Policy, Academic development, Integration of healthcare information system,
      Research in primary care, Utility and safety evaluation, and Practice
      transformation. The current healthcare landscape is favourable to test out this
      multipronged approach. PCPs in both sectors can ride on it and work together
      synergistically to provide quality primary care in Singapore. 

PMID- 24664375
TI  - Education and training in family medicine: progress and a proposed national
      vision for 2030.
AB  - This review provides an update of education and training in family medicine in
      Singapore and worldwide. Family medicine has progressed much since 1969 when it
      was recognised as the 20th medical discipline in the United States. Three salient
      changes in the local healthcare landscape have been noted over time, which are of
      defining relevance to family medicine in Singapore, namely the rise of
      noncommunicable chronic diseases, the care needs of an expanding elderly
      population, and the care of a larger projected population in 2030. The change in
      the vision of family medicine into the future refers to a new paradigm of one
      discipline in many settings, and not limited to the community. Family medicine
      needs to provide a patient-centred medical home, and the discipline's education
      and training need to be realigned. The near-term training objectives are to
      address the service, training and research needs of a changing and challenging
      healthcare landscape. 

PMID- 24664376
TI  - Education and training in family medicine: looking ahead.

PMID- 24664377
TI  - Healthcare in Singapore: the present and future.

PMID- 24664378
TI  - Headaches in children.
AB  - Headaches are common in children. Common primary headaches can also be
      experienced by children. The most common causes of innocent headaches among
      children are tiredness, shortsightedness, viral fever, sinusitis and psychosocial
      stressors. Consultation tasks include an attempt to diagnose the headache, the
      exclusion of sinister causes, and an effort to address any underlying concerns
      that the child and his/her family members may have. At a busy primary care
      consultation, the use of a headache symptom diary may provide important
      information for the evaluation of children presenting with chronic headaches. 

PMID- 24664379
TI  - The influence of caregivers' knowledge and understanding of asthma aetiology on
      domiciliary management of children with asthma.
AB  - INTRODUCTION: Asthma is a common childhood disease, and paediatric patients with
      asthma rely on caregivers to administer domiciliary asthma care. This study aimed
      to explore the knowledge, understanding, perceptions and main concerns of
      caregivers and its influence on their home management of children with asthma.
      METHODS: Data from 14 caregivers of children with asthma was collected during
      three focus group discussions held in two polyclinics in Singapore. The collected
      data was analysed using standard content analysis and classified into themes.
      RESULTS: The caregivers' main concerns included the perceived effects of
      infection, food and exercise on children with asthma. Several caregivers
      considered the disease to be infectious and had a lower threshold for physician
      consultation, as they believed that any delay in treating the infection would be
      detrimental to the child's health. Some also perceived asthma to be episodic and
      self-limiting, and that their children could 'outgrow' it. Many caregivers
      believed that asthma could be modified by abstinence from, or intake of, certain
      foods. Others had the perception that sports, including swimming, would worsen
      asthma. These perceptions resulted in unnecessary restrictions of the children's
      diet and activities. Most caregivers were unaware of influenza vaccination as a
      preventive measure to reduce triggers due to respiratory viral infections.
      CONCLUSION: We found that the caregivers' perceptions of asthma aetiology, its
      triggers and preventive measures affected their help-seeking behaviour and care
      of children with asthma. Healthcare professionals managing paediatric patients
      with asthma should recognise such caregiver misperceptions, and take a proactive
      approach to rectify and bridge the gaps in caregivers' knowledge and
      understanding of the disease.

PMID- 24664380
TI  - Parental knowledge, attitudes and perceptions regarding infant basic life
      support.
AB  - INTRODUCTION: Out-of-hospital cardiopulmonary arrest (CPA) in children is rare
      but significant, with poor survival rates and high morbidity. Asystole is the
      most common dysrhythmia, and cardiopulmonary resuscitation (CPR) is of great
      importance in such cases. We aimed to survey the knowledge, attitudes and
      perceptions of parents in Singapore regarding infant basic life support (IBLS).
      METHODS: A questionnaire survey was administered to parents of children managed
      at the Neonatal Department of Singapore General Hospital, Singapore, between 1
      September and 31 December 2008. The questionnaire consisted of three sections-
      section A collected demographic data, section B included questions on knowledge,
      and section C explored attitudes and perceptions. Knowledge T-scores were
      analysed for the entire cohort and subanalysed with respect to prior IBLS
      training. RESULTS: In our study cohort (n = 375), the median Basic Knowledge (BK)
      T-score was 7 (range 1-9) and the pass rate was 55%. Median BK T-scores were
      significantly different between untrained (6; range 3-9) and previously trained
      (8; range 3-9) participants. A majority of the trained participants obtained pass
      marks. Median Total Knowledge T-score, involving advanced questions, for
      previously trained participants was 11 (range 3-14), but pass rate was low
      (35.7%). Higher educational qualification was a significant factor impacting all
      scores. Untrained participants indicated interest in attending IBLS courses,
      while trained participants were interested in refresher courses. CONCLUSION: IBLS
      training, as part of basic cardiac life support training, is important given that
      CPR can significantly alter the outcome in children with CPA. Our survey revealed
      knowledge gaps that could be bridged through formal training. Refresher courses
      to regularly update parents' knowledge are recommended.

PMID- 24664381
TI  - Incidence of discontinuation of angiotensin-converting enzyme inhibitors due to
      cough, in a primary healthcare centre in Singapore.
AB  - INTRODUCTION: The incidence of cough induced by angiotensin-converting enzyme
      (ACE) inhibitors has been reported to be 5%-20%, with less than half of affected
      patients requiring discontinuation due to persistent cough. However, the
      incidence in the local Asian population has not been studied. This study aimed to
      objectively evaluate the incidence of discontinuation of ACE inhibitors due to
      cough, in a primary healthcare centre in Singapore. METHODS: We retrospectively
      reviewed the medical records, both electronic and written, of patients who
      attended Tampines Polyclinic to identify those who were newly prescribed ACE
      inhibitors. The written medical records were analysed to identify patients who
      discontinued the use of ACE inhibitors and to find out the reasons for
      discontinuation. RESULTS: A total of 424 patients were identified during the
      study period. Out of the 424 patients, 129 (30.4%) discontinued the use of ACE
      inhibitors due to cough. Overall, 90 (21.2%) patients who were initially started
      on ACE inhibitors were eventually switched to angiotensin receptor blockers
      (ARBs). CONCLUSION: In our cohort, the incidence of discontinuation of ACE
      inhibitors due to cough is higher than most other studies. The relationship
      between ethnicity and tolerance of medications should not be underestimated. As
      there is a high incidence of discontinuation of ACE inhibitors due to cough in
      the local population, ARBs may be a reasonable substitute as a first-line
      medication, if clinically indicated.

PMID- 24664382
TI  - Demographic profile, clinical characteristics, motivations and weight loss
      outcomes of patients in a nonsurgical weight management programme.
AB  - INTRODUCTION: Weight management programmes (WMPs) can help overweight individuals
      lose weight, and thus prevent complications associated with obesity. Herein, we
      describe the demographic profile, clinical characteristics, motivations and
      expectations, and outcomes of patients enrolled in a nonsurgical WMP. METHODS:
      This was a retrospective study of consecutive patients with a body mass index
      (BMI) of > 23 kg/m2 enrolled in the four-month WMP at the Health For Life Clinic,
      Alexandra Hospital, Singapore, between 1 and 31 August 2009. Demographic data,
      medical history and source of referral were recorded. Details on personal
      motivations and weight loss goals were obtained from the completed self
      administered questionnaires of the WMP participants. Weight, waist circumference,
      fat percentage and BMI were measured at the start and end of the WMP. A weight
      loss of >= 5% was deemed as a successful outcome. RESULTS: A total of 58 patients
      (mean age 37.2 years) were included in our study. Of these 58 patients, 58.6%
      were of Chinese ethnicity and 55.2% were male. Many patients (32.8%) attributed
      their weight gain to work- or study-related stress, and a minority to poor eating
      habits (12.1%) or a lack of exercise (10.3%). Patients' motivations included a
      desire for better health (53.4%) and better fitness (15.5%). However, only 53.4%
      patients scored their motivation as high (i.e. a score of > 7). The mean expected
      weight loss was 9.9 kg at 4 months, and 14.1 kg at 12 months. Among the 40
      patients (69.0%) who completed the programme, the mean percentage weight loss was
      1.8 +/- 4.3%. A weight loss of >= 5% was achieved by 8 (13.8%) patients.
      CONCLUSION: Although the patients in our study cohort were young and educated,
      only a portion of them appeared to be highly motivated to lose weight, despite
      joining the WMP. There is a need for patients to be guided on how to set
      realistic weight loss goals.

PMID- 24664383
TI  - How do primary care physicians in Singapore keep healthy?
AB  - INTRODUCTION: Not much is known regarding how primary care physicians (PCPs) in
      Singapore keep themselves healthy and mitigate ill health. This study aims to
      determine the health-seeking behaviour of local PCPs and to identify the
      predictors of local PCPs attaining the recommended level of exercise. METHODS:
      This study was a cross-sectional questionnaire survey, which included questions
      on the demographic characteristics, practice profiles and health-seeking
      behaviour of PCPs. The sampling frame was the 1,400 listed members of the College
      of Family Physicians Singapore. The anonymised survey was executed in two phases:
      a postal survey, followed by a web-based survey on the College of Family
      Physicians Singapore website. The two data sets were collated; the categorical
      variables, summarised; and the differences between subgroups (based on exercise
      engagement), compared using Fisher's exact test. The effect of each risk factor
      on exercise duration was quantified using odds ratio (OR) estimate and 95%
      confidence interval (CI). Multivariate logistic regression analysis was performed
      to identify significant predictors of exercise engagement. RESULTS: A total of
      631 PCPs participated in the survey--26% were <= 34 years old, 58% were male, 21%
      were single, 34% were singleton practitioners, and 56% were private
      practitioners. The percentage of PCPs who exercised >= 2.5 hours weekly was 29%,
      while 28% exercised < 0.5 hours weekly. Of the PCPs surveyed, 1% currently smoke,
      0.8% drink more than 14 units of alcohol weekly, 60% undertook health screening,
      65% had blood investigations done, and 64% had taken preventive measures such as
      getting influenza vaccination. CONCLUSION: While local PCPs generally did not
      have undesirable habits such as smoking and alcohol abuse, they could further
      increase their exercise intensity and undertake more preventive measures such as
      getting vaccinated against various diseases.

PMID- 24664384
TI  - The use of facemasks to prevent respiratory infection: a literature review in the
      context of the Health Belief Model.
AB  - INTRODUCTION: Acute respiratory infections are prevalent and pose a constant
      threat to society. While the use of facemasks has proven to be an effective
      barrier to curb the aerosol spread of such diseases, its use in the local
      community is uncommon, resulting in doubts being cast on its effectiveness in
      preventing airborne infections during epidemics. We thus aimed to conduct a
      literature review to determine the factors that influence the use of facemasks as
      a primary preventive health measure in the community. METHODS: A search for
      publications relating to facemask usage was performed on Medline, PubMed, Google,
      World Health Organization and Singapore government agencies' websites, using
      search terms such as 'facemask', 'mask', 'influenza', 'respiratory infection',
      'personal protective equipment', 'disease prevention', 'compliance' and
      'adherence'. Findings were framed under five components of the Health Belief
      Model: perceived susceptibility, perceived benefits, perceived severity,
      perceived barriers and cues to action. RESULTS: We found that individuals are
      more likely to wear facemasks due to the perceived susceptibility and perceived
      severity of being afflicted with life-threatening diseases. Although perceived
      susceptibility appeared to be the most significant factor determining compliance,
      perceived benefits of mask-wearing was found to have significant effects on mask
      wearing compliance as well. Perceived barriers include experience or perception
      of personal discomfort and sense of embarrassment. Media blitz and public health
      promotion activities supported by government agencies provide cues to increase
      the public's usage of facemasks. CONCLUSION: Complex interventions that use
      multipronged approaches targeting the five components of the Health Belief Model,
      especially perceived susceptibility, are needed to increase the use of facemasks
      in the community. Further studies are required to evaluate the effectiveness of
      implemented interventions.

PMID- 24664385
TI  - Inflammatory breast cancer: a clinical diagnosis.

PMID- 24664386
TI  - Authors' reply: Inflammatory breast cancer: a clinical diagnosis.

PMID- 24664387
TI  - Preventing hearing loss from portable music player use.

PMID- 24664388
TI  - Authors' reply: Preventing hearing loss from portable music player use.

PMID- 24664390
TI  - Portobiliary fistula: successful transcatheter treatment with embolisation coils.
AB  - Although portobiliary fistula is a recognised complication of percutaneous
      transhepatic biliary drainage, it is extremely uncommon and can result in
      haemobilia. Herein, we present a case of complicated transhepatic biliary
      drainage catheter insertion in a patient with underlying hepatitis B liver
      cirrhosis, which resulted in a portobiliary fistula. The patient had a
      preoperative transhepatic biliary drainage procedure done prior to a Whipple's
      operation for a large, obstructive, gastrointestinal stromal tumour of the
      duodenum. To the best of our knowledge, this is the first case in the English
      medical literature reporting the successful treatment of portobiliary fistula by
      embolisation of its tract with embolisation coils, without compromising the
      portal vein or bile ducts. 

PMID- 24664391
TI  - Extracorporeal life support for cardiac arrest in a paediatric emergency
      department.
AB  - The initiation of extracorporeal membrane oxygenation (ECMO) in the emergency
      department (ED) is a rare event. Herein, we report a case of acute fulminant
      myocarditis in a nine-year-old girl who was successfully resuscitated by early
      initiation of ECMO support in the paediatric ED of KK Women's and Children's
      Hospital, Singapore. The patient had rapidly progressed into a witnessed
      pulseless ventricular tachycardia on presentation, and ECMO was started in the ED
      following the failure of standard resuscitation measures to establish spontaneous
      circulation. ECMO was continued for nine days. The patient recovered well with
      normal neurocognitive function. The initiation of ECMO in the ED is potentially
      life-saving in the resuscitation of children with witnessed in-hospital cardiac
      arrest due to a reversible cause.

PMID- 24664392
TI  - Bilateral rectus sheath blocks as the single anaesthetic technique for an open
      infraumbilical hernia repair.
AB  - We present a case of an open surgical repair of an infraumbilical hernia, which
      was performed on a 45-year-old man categorised as American Society of
      Anesthesiologists class 4; he weighed 107 kg, and had a body mass index of 34.2
      kg/m2 and nonischaemic cardiomyopathy (left ventricular ejection fraction of
      20%). Due to the patient's significant perioperative risks, the surgery was
      performed with the patient under ultrasonography-guided bilateral rectus sheath
      blocks; 15 mL of 1% lignocaine and 10 mL of 0.5% bupivacaine were deposited in
      the space between the rectus abdominis and posterior rectus sheath. The patient
      tolerated the surgery with minimal further sedation and additional analgesia.
      Rectus sheath block is a useful regional technique for periumbilical surgery,
      allowing surgery in highrisk patients while avoiding general anaesthesia and
      central neuraxial blockade. The use of real-time ultrasonographic guidance may
      reduce risks of peritoneal puncture, bleeding and visceral injury, while
      potentially increasing the rate of success. 

PMID- 24664393
TI  - Isolated metastatic papillary thyroid carcinoma masquerading as parapharyngeal
      space paraganglioma.
AB  - Isolated metastatic deposits of papillary thyroid carcinoma to the parapharyngeal
      space are rare. Herein, we describe the case of a young woman who presented with
      a right-sided oropharyngeal mass that was initially diagnosed as a parapharyngeal
      space paraganglioma. The patient opted for conservative treatment as she was
      asymptomatic and wished to avoid the risk of neurovascular morbidity associated
      with surgery. After 20 years, the patient sought treatment again for the
      oropharyngeal mass, which had progressively increased in size and was causing
      difficulty in swallowing. Repeat imaging of the affected area revealed that the
      mass had increased significantly in size; it also revealed the presence of a
      previously absent small lesion in the right lobe of the thyroid. Excision of the
      parapharyngeal space tumour and near-total thyroidectomy were performed; the
      excised specimens showed features of the follicular variant of papillary thyroid
      carcinoma. As papillary thyroid carcinoma that metastasises to the parapharyngeal
      space can masquerade as a paraganglioma, clinicians should bear in mind that an
      isolated metastatic deposit in the parapharyngeal space could be the first sign
      of occult papillary thyroid carcinoma. 

PMID- 24664394
TI  - Tension pneumocephalus.
AB  - Tension pneumocephalus is a rare but treatable neurosurgical emergency. Prompt
      and accurate diagnosis of tension pneumocephalus requires a high index of
      clinical suspicion corroborated by imaging. Herein, we describe a case of
      extensive tension pneumocephalus in a patient who had undergone transsphenoidal
      surgery and repair of the sellar floor, with subsequent successful decompression.
      This case report discusses the pertinent imaging features of tension
      pneumocephalus and its management. 

PMID- 24664395
TI  - Clear cell chondrosarcoma with secondary aneurysmal bone cyst changes.
AB  - Clear cell chondrosarcoma is a rare cartilaginous tumour of low-grade malignancy.
      Although it has a characteristic histological appearance, its radiological
      features and clinical presentation often mimic a benign lesion. Herein, we
      describe the case of a patient with a clear cell chondrosarcoma of the right
      proximal femur that had an atypical appearance of chronic avascular necrosis on
      initial plain radiographs, which made preoperative diagnosis a challenge. In
      addition, the tumour also had extensive areas of aneurysmal bone cyst-like
      changes, which is not only a rare histologic phenomenon in clear cell
      chondrosarcoma, but also a confounding factor in the interpretation of the
      radiologic findings. 

PMID- 24664396
TI  - Age-at-death estimation based on radiological and image analysis methods in
      clavicle in a current Spanish population.
AB  - Age-at-death estimation in adult individuals is one of the most challenging
      issues in forensic anthropology, namely, due to the large age intervals provided
      by the current methods, which demand the development of more reliable
      investigations. The clavicle has been studied as an age-at-death indicator in
      many researches for its accessibility, low biomechanical implication in
      locomotion and accuracy to predict age at death when other age indicators are not
      available. The present study was developed on a sample of 332 clavicles from
      adult individuals of known sex and age from the current Spanish population. They
      were x-rayed and digitalized, in a standardized way, using a Sedecal X-ray
      generator, model SHF 415. Three indices were calculated at the mid-diaphysis
      point (anterior index, posterior index, and total index) which relate the
      cortical thickness and the total clavicle thickness to age at death. The average
      grey level was also calculated in a 0.5-cm(2) area of the sternal and acromial
      ends (sternal grey average, acromial grey average), using Image J software. The
      data were subjected to a statistical analysis, using SPSS, version 15.0. The
      results show that average grey level has a weaker correlation with age than the
      variables which are based on the cortical thickness. On the other hand, the
      regression equations, which were calculated combining all the variables, provided
      smaller age-at-death intervals, demonstrating the usefulness of this method for
      adult age-at-death estimation in forensic anthropology. 

PMID- 24664398
TI  - Following ORR intermediates adsorbed on a Pt cathode catalyst during break-in of
      a PEM fuel cell by in operando X-ray absorption spectroscopy.
AB  - In operando X-ray absorption spectroscopy data using the DeltaMU X-ray Absorption
      Near Edge Spectroscopy (XANES) analysis procedure is used to follow the ORR
      intermediate adsorbate coverage on a working catalyst in a PEMFC during initial
      activation and break-in. The adsorbate coverage and log i (Tafel) curves reveal a
      strong correlation, i.e., an increase in adsorbate intermediate coverage poisons
      Pt sites thereby decreasing the current. A decrease in Pt-O bond strength
      commensurate with decrease in potential causes a sequence of different dominant
      adsorbate volcano curves to exist, namely first O, then OH, and then OOH exactly
      as predicted by the different ORR kinetics mechanisms. During break-in, the
      incipient O coverage coming from exposure to air during storage and MEA
      preparation is rather quickly removed, compared to the slower and more subtle
      nanoparticle morphological changes, such as the rounding of the Pt nanoparticle
      edges/corners and smoothing of the planar surfaces, driven by the nanoparticle's
      tendency to lower its surface energy. These morphological changes increase the Pt
      Pt average coordination number, decrease the average Pt-O bond strength, and
      thereby decrease the coverage of ORR intermediates, allowing increase in the
      current. 

PMID- 24664397
TI  - Chronic hepatitis C in the aged: much ado about nothing or nothing to do?
AB  - Hepatitis C is a common infection worldwide. It is a major cause of cirrhosis and
      its complications, including hepatocellular carcinoma and liver transplantation.
      Treatment of hepatitis C has dramatically improved since its discovery. Current
      treatment includes pegylated interferon and ribavirin, and the addition of the
      protease inhibitors telaprevir, boceprevir, or simeprevir, or the polymerase
      inhibitor sofosbuvir. The rate of sustained viral response, considered a cure,
      now approaches 80 %. These treatments are complex, with multiple morbidities and
      drug interactions. The majority of patients with chronic hepatitis C are from the
      birth cohort of the 'baby boomer' years (1945-1965) with the oldest already 68
      years old. In spite of this, most hepatitis C patients in clinical trials have
      been much younger and this is still the case in the ongoing studies. Thus, the
      group of patients most likely to require treatment in the future will have
      decisions made with a relative lack of evidence-based medicine. It is the purpose
      of this article to review the epidemiology, clinical manifestations, and
      treatment of hepatitis C with the data available in the aged population.

PMID- 24664400
TI  - Quantification of integrated HIV DNA by repetitive-sampling Alu-HIV PCR on the
      basis of poisson statistics.
AB  - BACKGROUND: Quantification of integrated proviral HIV DNA by repetitive-sampling
      Alu-HIV PCR is a candidate virological tool to monitor the HIV reservoir in
      patients. However, the experimental procedures and data analysis of the assay are
      complex and hinder its widespread use. Here, we provide an improved and
      simplified data analysis method by adopting binomial and Poisson statistics.
      METHODS: A modified analysis method on the basis of Poisson statistics was used
      to analyze the binomial data of positive and negative reactions from a 42
      replicate Alu-HIV PCR by use of dilutions of an integration standard and on
      samples of 57 HIV-infected patients. Results were compared with the quantitative
      output of the previously described Alu-HIV PCR method. RESULTS: Poisson-based
      quantification of the Alu-HIV PCR was linearly correlated with the standard
      dilution series, indicating that absolute quantification with the Poisson method
      is a valid alternative for data analysis of repetitive-sampling Alu-HIV PCR data.
      Quantitative outputs of patient samples assessed by the Poisson method correlated
      with the previously described Alu-HIV PCR analysis, indicating that this method
      is a valid alternative for quantifying integrated HIV DNA. CONCLUSIONS: Poisson
      based analysis of the Alu-HIV PCR data enables absolute quantification without
      the need of a standard dilution curve. Implementation of the CI estimation
      permits improved qualitative analysis of the data and provides a statistical
      basis for the required minimal number of technical replicates.

PMID- 24664399
TI  - Spectroscopic localization by simultaneous acquisition of the double-spin and
      stimulated echoes.
AB  - PURPOSE: To design a proton MR spectroscopy ((1) H-MRS) localization sequence
      that combines the signal-to-noise-ratio (SNR) benefits of point resolved
      spectroscopy (PRESS) with the high pulse bandwidths, low chemical shift
      displacements (CSD), low specific absorption rates (SAR), short echo times (TE),
      and superior radiofrequency transmit field (B1+) immunity of stimulated echo
      acquisition mode (STEAM), by simultaneously refocusing and acquiring both the
      double-spin and stimulated echo coherence pathways from the volume of interest.
      THEORY AND METHODS: We propose a family of (1)H-MRS sequences comprising three
      orthogonal spatially selective pulses with flip angles 90 degrees  < alpha, beta,
      gamma < 128 degrees . The stimulated and double-spin echo are refocused in-phase
      simultaneously by altering the pulses' phases, flip angles and timing, as well as
      the interpulse gradient spoiling moments. The ~ 90 degrees  nutations of alpha,
      beta, gamma provide STEAM-like advantages (lower SAR, in-plane CSD and TE;
      greater B1+ immunity), but with SNRs comparable with PRESS. RESULTS: Phantom and
      in vivo brain experiments show that 83-100% of the PRESS SNR (metabolite
      dependent) is achieved at under 75% of the SAR and 66% lower in-plane CSD.
      CONCLUSION: The advantages of STEAM can be augmented with the higher SNR of PRESS
      by combining the spin and stimulated echoes. Quantification, especially of J
      coupled resonances and intermediate and long TEs, must be carefully considered.

PMID- 24664401
TI  - Lot-to-lot variations in a qualitative lateral-flow immunoassay for chronic pain
      drug monitoring.

PMID- 24664403
TI  - Colloidal plasmonic back reflectors for light trapping in solar cells.
AB  - A novel type of plasmonic light trapping structure is presented in this paper,
      composed of metal nanoparticles synthesized in colloidal solution and self
      assembled in uniform long-range arrays using a wet-coating method. The high
      monodispersion in size and spherical shape of the gold colloids used in this work
      allows a precise match between their measured optical properties and
      electromagnetic simulations performed with Mie theory, and enables the full
      exploitation of their collective resonant plasmonic behavior for light-scattering
      applications. The colloidal arrays are integrated in plasmonic back reflector
      (PBR) structures aimed for light trapping in thin film solar cells. The PBRs
      exhibit high diffuse reflectance (up to 75%) in the red and near-infrared
      spectrum, which can pronouncedly enhance the near-bandgap photocurrent generated
      by the cells. Furthermore, the colloidal PBRs are fabricated by low-temperature
      (<120  degrees C) processes that allow their implementation, as a final step of
      the cell construction, in typical commercial thin film devices generally
      fabricated in a superstrate configuration. 

PMID- 24664402
TI  - Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013
      II. Extrapancreatic lesions, differential diagnosis.

PMID- 24664404
TI  - An evaluation of sucrose as a possible contaminant in e-liquids for electronic
      cigarettes by hydrophilic interaction liquid chromatography-tandem mass
      spectrometry.
AB  - The influence of sucrose combustion products on smoking and nicotine addiction is
      still controversial because the presence of the sucrose may be treated as a
      source of aldehydes and organic acids. In e-liquids used as refills for
      electronic cigarettes, which are made primarily of poly(propylene glycol),
      glycerine and ethanol, sucrose may be present at trace levels, and its impact on
      mainstream smoke formation, and hence on human health and smoking/nicotine
      addiction is unknown. An analytical method was developed where high-performance
      liquid chromatography in hydrophilic interaction liquid chromatography mode and
      tandem mass spectrometry were used for fast and simple determination of sucrose
      and other saccharides in e-liquids for electronic cigarettes. Minimal effort was
      required in the sample preparation step, and satisfactory results were obtained,
      and the sample matrix had an insignificant impact. The chromatographic separation
      was done using an Ascentis Express OH5 column (150 mm * 2.1 mm, 2.7 MUm). The
      coefficients of variation for within-day precision for three concentrations were
      2.4 %, 1.6 % and 2.3 %, and the between-day coefficients of variation for a
      single concentration were 2.1 %, 2.5 % and 1.7 % measured on the next 3 days. The
      detection limit was 0.73 MUg/g, and the sucrose content in e-liquids ranged from
      0.76 to 72.93 MUg/g among 37 samples. Moreover, with the method presented it is
      possible to determine the presence of other saccharides such as fructose,
      glucose, maltose and lactose. However, only sucrose was found in all samples of e
      liquids. The proposed method is rapid, simple and reliable in terms of high
      performance liquid chromatography coupled with tandem mass spectrometry.

PMID- 24664405
TI  - Recent advances and future developments in forensic toxicology.

PMID- 24664406
TI  - Characterization of heparin-protein interaction by saturation transfer difference
      (STD) NMR.
AB  - The binding affinity and specificity of heparin to proteins is widely recognized
      to be sulfation-pattern dependent. However, for the majority of heparin-binding
      proteins (HBPs), it still remains unclear what moieties are involved in the
      specific binding interaction. Here, we report our study using saturation transfer
      difference (STD) nuclear magnetic resonance (NMR) to map out the interactions of
      synthetic heparin oligosaccharides with HBPs, such as basic fibroblast growth
      factor (FGF2) and fibroblast growth factor 10 (FGF10), to provide insight into
      the critical epitopes of heparin ligands involved. The irradiation frequency of
      STD NMR was carefully chosen to excite the methylene protons so that enhanced
      sensitivity was obtained for the heparin-protein complex. We believe this
      approach opens up additional application avenues to further investigate heparin
      protein interactions. 

PMID- 24664407
TI  - Novel MU-membrane module for online determination of the free fatty acid content
      in the dispersed phase of oil-in-water emulsions.
AB  - Monitoring the dispersed phase of an oil-in-water (O-W) emulsion by means of
      Fourier transform infrared (FTIR) spectroscopy is a challenging task, restricted
      to the continuous phase that is in contact with the FTIR probe. Nonetheless, real
      time measurement and kinetic analysis by FTIR, including analysis of the
      dispersed, often non-polar phase containing substrates and/or products, is
      desirable. Enzymatic hydrolysis of sunflower oil was performed in an O-W
      emulsion. After separation of the oil phase by use of a newly developed MU
      membrane module, infrared spectra were collected using an attenuated total
      reflectance (ATR) cell. Different chemometric models were calibrated using the
      partial least squares (PLS) algorithm. Online application of a chemometric model
      based on the FTIR spectra enabled real-time monitoring of free fatty acid
      concentrations in the oil phase. 

PMID- 24664408
TI  - Water, water, everywhere, and not a drop to drink.

PMID- 24664409
TI  - The dangers of plug-and-play simulation using shared models.

PMID- 24664410
TI  - Self-consistent field theory of block copolymers on a general curved surface.
AB  - In this work, we propose a theoretical framework based on the self-consistent
      field theory (SCFT) for the study of self-assembling block copolymers on a
      general curved surface. Relevant numerical algorithms are also developed. To
      demonstrate the power of the approach, we calculate the self-assembled patterns
      of diblock copolymers on three distinct curved surfaces with different genus. We
      specially study the geometrical effects of curved surfaces on the conformation of
      polymer chains as well as on the pattern formation of block copolymers. By
      carefully examining the diffusion equation of the propagator on curved surfaces,
      it is predicted that Gaussian chains are completely unaware of the extrinsic
      curvature but that they will respond to the intrinsic curvature of the surface.
      This theoretical assertion is consistent with our SCFT simulations of block
      copolymers on general curved surfaces. 

PMID- 24664411
TI  - Prion (PrPC) expression in ovine uteroplacental tissues increases after estrogen
      treatment of ovariectomized ewes and during early pregnancy.
AB  - Scrapie in sheep is spread laterally by placental transmission of an infectious
      misfolded form (PrPSc) of a normal prion protein (PrPC) used as a template in
      PrPSc formation. We hypothesized that PrPC would be expressed in uterine and
      placental tissues and estradiol-17beta (E2) would affect uterine PrPC expression.
      PrPC expression was evaluated in the uterus of long-term ovariectomized (OVX)
      ewes treated with an E2 implant for 2-24 h and in uteroplacental tissues from day
      20 to day 30 of pregnancy. Expression of PrPC mRNA and PrPC protein increased in
      the uterus after E2 treatment of OVX ewes. In the maternal placenta, expression
      of PrPC mRNA and PrPC protein were unchanged, but in the fetal membranes (FM)
      PrPC mRNA and PrPC protein expression increased from day 20 to day 28. In the
      nonpregnant uterus, PrPC protein was immunolocalized at apical borders of the
      surface epithelium, in outer smooth muscle layers of large blood vessels, and in
      scattered stromal cells of the deep intercaruncular areas of the uterus. In the
      maternal placenta, PrPC protein was immunolocalized in the cytoplasm of flattened
      luminal epithelial cells apposed to the FM, whereas in the FM PrPC protein was in
      trophoblast cells and was also in several tissues of the developing embryo during
      early pregnancy. These data linking estrogen stimulation to increases in PrPC
      expression in uteroplacental tissues suggest that PrPC has a specific function
      during the estrous cycle and early pregnancy. Future studies should determine
      whether or not estrogen influences PrPC expression in other tissues, such as the
      nervous system and brain. 

PMID- 24664412
TI  - Controlled-release systems for metal-based nanomedicine: encapsulated/self
      assembled nanoparticles of anticancer gold(III)/platinum(II) complexes and
      antimicrobial silver nanoparticles.
AB  - The therapeutic applications of many anticancer or antimicrobial metal complexes
      often suffer from low solubility and low stability in physiological conditions or
      from drug resistance. To circumvent these problems, nanoparticle systems that
      allow controlled release and specific accumulation in the targeted disease tissue
      are of advantage for efficient treatment with minimal toxicity. The focus of this
      Research News is metal-based nanomaterials comprising anticancer
      gold(III)/platinum(II) complexes or antimicrobial silver, highlighting the
      controlled-release properties of self-assembled metal systems. 

PMID- 24664413
TI  - From the journal archives: Pulmonary marrow embolism: lessons learned from a
      canine model simulating dual component cemented arthroplasty.

PMID- 24664414
TI  - Transfer of learning and patient outcome in simulated crisis resource management:
      a systematic review.
AB  - PURPOSE: Simulation-based learning is increasingly used by healthcare
      professionals as a safe method to learn and practice non-technical skills, such
      as communication and leadership, required for effective crisis resource
      management (CRM). This systematic review was conducted to gain a better
      understanding of the impact of simulation-based CRM teaching on transfer of
      learning to the workplace and subsequent changes in patient outcomes. SOURCE:
      Studies on CRM, crisis management, crew resource management, teamwork, and
      simulation published up to September 2012 were searched in MEDLINE((r)),
      EMBASETM, CINAHL, Cochrane Central Register of Controlled Trials, and ERIC. All
      studies that used simulation-based CRM teaching with outcomes measured at
      Kirkpatrick Level 3 (transfer of learning to the workplace) or 4 (patient
      outcome) were included. Studies measuring only learners' reactions or simple
      learning (Kirkpatrick Level 1 or 2, respectively) were excluded. Two authors
      independently reviewed all identified titles and abstracts for eligibility.
      PRINCIPAL FINDINGS: Nine articles were identified as meeting the inclusion
      criteria. Four studies measured transfer of simulation-based CRM learning into
      the clinical setting (Kirkpatrick Level 3). In three of these studies, simulation
      enhanced CRM training was found significantly more effective than no intervention
      or didactic teaching. Five studies measured patient outcomes (Kirkpatrick Level
      4). Only one of these studies found that simulation-based CRM training made a
      clearly significant impact on patient mortality. CONCLUSIONS: Based on a small
      number of studies, this systematic review found that CRM skills learned at the
      simulation centre are transferred to clinical settings, and the acquired CRM
      skills may translate to improved patient outcomes, including a decrease in
      mortality.

PMID- 24664415
TI  - Contrast-enhanced harmonic endoscopic ultrasonography in the differential
      diagnosis of gallbladder wall thickening.
AB  - BACKGROUND AND AIMS: Differentiation of gallbladder (GB) carcinoma from benign GB
      wall thickening is challenging. The recent introduction of second-generation
      ultrasonic contrast agents has made contrast harmonic imaging with EUS possible.
      The aim of our study was to evaluate the utility of contrast-enhanced harmonic
      EUS (CH-EUS) for the differential diagnosis of GB wall thickening. METHODS:
      Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then
      underwent surgery were enrolled in this study. After the lesions were observed
      with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous
      injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of
      experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C:
      experienced gastroenterologist with expertise in transabdominal ultrasound but no
      EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS.
      The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was
      compared. RESULTS: Final diagnoses based on surgical histology were GB carcinoma
      in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3.
      Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall
      thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98% (p < 0.001)
      and 73.1 versus 94.4% (p < 0.001). The inter-observer agreement for H-EUS was
      moderate (kappa = 0.51), whereas that for CH-EUS was substantial (kappa = 0.77).
      The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of
      malignant GB wall thickening. CONCLUSION: CH-EUS has the potential to improve the
      preoperative diagnostic accuracy and inter-observer agreement in the differential
      diagnosis of GB wall thickening.

PMID- 24664416
TI  - Exploiting aromatic interactions for beta-peptide foldamer helix stabilization: a
      significant design element.
AB  - Tetrameric H10/12 helix stabilization was achieved by the application of aromatic
      side-chains in beta-peptide oligomers by intramolecular backbone-side chain CH-pi
      interactions. Because of the enlarged hydrophobic surface of the oligomers, a
      further aim was the investigation of the self-assembly in a polar medium for the
      beta-peptide H10/12 helices. NMR, ECD, and molecular modeling results indicated
      that the oligomers formed by cis-[1S,2S]- or cis-[1R,2R]-1-amino-1,2,3,4
      tetrahydronaphthalene-2-carboxylic acid (ATENAC) and cis-[1R,2S]- or cis-[1S,2R]
      2-aminocyclohex-3-enecarboxylic acid (ACHEC) residues promote stable H10/12 helix
      formation with an alternating backbone configuration even at the tetrameric chain
      length. These results support the view that aromatic side-chains can be applied
      for helical structure stabilization. Importantly, this is the first observation
      of a stable H10/12 helix with tetrameric chain-length. The hydrophobically driven
      self-assembly was achieved for the helix-forming oligomers, seen as vesicles in
      transmission electron microscopy images. The self-association phenomenon, which
      supports the helical secondary structure of these oligomers, depends on the
      hydrophobic surface area, because a higher number of aromatic side-chains yielded
      larger vesicles. These results serve as an essential element for the design of
      helices relating to the H10/12 helix. Moreover, they open up a novel area for
      bioactive foldamer construction, while the hydrophobic area gained through the
      aromatic side-chains may yield important receptor-ligand interaction surfaces,
      which can provide amplified binding strength. 

PMID- 24664417
TI  - Effects of lithium and lamotrigine on oxidative-nitrosative stress and spatial
      learning deficit after global cerebral ischemia.
AB  - Lithium (Li) and lamotrigine (LTG) have neuroprotective properties. However, the
      exact therapeutic mechanisms of these drugs have not been well understood. We
      investigated the antioxidant properties of Li (40 and 80 mg/kg/day) and LTG (20
      and 40 mg/kg/day) in a rat model of global cerebral ischemia based on permanent
      bilateral occlusion of the common carotid arteries (BCAO). Nitric oxide (NO),
      malondialdehyde (MDA), glutathione (GSH), glutathione reductase (GSH-R), catalase
      (CAT) and superoxide dismutase (SOD) levels were measured as an indicator of
      oxidative-nitrosative stress in both prefrontal cortex (PFC) and hippocampus
      after 28 days of treatment. The spatial learning disability was also assessed at
      the end of the study by Morris water maze (MWM) test. All oxidative-nitrosative
      parameters were found to be higher in the groups under treatment than in sham.
      Both drugs caused a decrease in PFC NO and MDA elevation, meanwhile the increase
      in GSH, GSH-R, CAT and SOD levels was significantly more evident in treated
      groups. We also found higher PFC GSH-R and hippocampal SOD levels in BCAO + Li
      (80 mg/day) treated group when compared with BCAO + LTG 40 mg/day. MWM test data
      showed a similar increase in spatial learning ability in all groups under
      treatment. We found no other statistical difference in comparison of treated
      groups with different dosages. Our findings suggested that Li and LTG treatments
      may decrease spatial learning memory deficits accompanied by lower oxidative
      nitrosative stress in global cerebral ischemia. Both drugs may have potential
      benefits for the treatment of vascular dementia in clinical practice.

PMID- 24664418
TI  - Antiretroviral protease inhibitors accelerate glutathione export from viable
      cultured rat neurons.
AB  - Antiretroviral protease inhibitors are crucial components of the antiretroviral
      combination therapy that is successfully used for the treatment of patients with
      HIV infection. To test whether such protease inhibitors affect the glutathione
      (GSH) metabolism of neurons, cultured cerebellar granule neurons were exposed to
      indinavir, nelfinavir, lopinavir or ritonavir. In low micromolar concentrations
      these antiretroviral protease inhibitors did not acutely compromise the cell
      viability, but caused a time- and concentration-dependent increase in the
      accumulation of extracellular GSH which was accompanied by a matching loss in
      cellular GSH. The stimulating effect by indinavir, lopinavir and ritonavir on GSH
      export was immediately terminated upon removal of the protease inhibitors, while
      the nelfinavir-induced stimulated GSH export persisted after washing the cells.
      The stimulation of neuronal GSH export by protease inhibitors was completely
      prevented by MK571, an inhibitor of the multidrug resistance protein 1,
      suggesting that this transporter mediates the accelerated GSH export during
      exposure of neurons to protease inhibitors. These data suggest that alterations
      in brain GSH metabolism should be considered as potential side-effects of a
      treatment with antiretroviral protease inhibitors. 

PMID- 24664419
TI  - Prostate stromal cells express the progesterone receptor to control cancer cell
      mobility.
AB  - BACKGROUND: Reciprocal interactions between epithelium and stroma play vital
      roles for prostate cancer development and progression. Enhanced secretions of
      cytokines and growth factors by cancer associated fibroblasts in prostate tumors
      create a favorable microenvironment for cancer cells to grow and metastasize. Our
      previous work showed that the progesterone receptor (PR) was expressed
      specifically in prostate stromal fibroblasts and smooth muscle cells. However,
      the expression levels of PR and its impact to tumor microenvironment in prostate
      tumors are poorly understood. METHODS: Immunohistochemistry assays are applied to
      human prostate tissue biopsies. Cell migration, invasion and proliferation assays
      are performed using human prostate cells. Real-time PCR and ELISA are applied to
      measure gene expression at molecular levels. RESULTS: Immunohistochemistry assays
      showed that PR protein levels were decreased in cancer associated stroma when
      compared with paired normal prostate stroma. Using in vitro prostate stromal cell
      models, we showed that conditioned media collected from PR positive stromal cells
      inhibited prostate cancer cell migration and invasion, but had minor suppressive
      impacts on cancer cell proliferation. PR suppressed the secretion of stromal
      derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to
      PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1
      or IL-6 to conditioned media from PR positive stromal cells counteracted the
      inhibitory effects of PR to cancer cell migration and invasion. CONCLUSIONS:
      Decreased expression of the PR in cancer associated stroma may contribute to the
      elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor
      progression.

PMID- 24664421
TI  - Anterior approach to the superior mesenteric artery by using nerve plexus hanging
      maneuver for borderline resectable pancreatic head carcinoma.
AB  - To achieve R0 resection for pancreatic ductal adenocarcinoma (PDAC) of the
      pancreatic head, complete resection of the retropancreatic nerve plexus around
      the superior mesenteric artery (SMA) is thought to be required. Twenty-five
      patients with borderline resectable right-sided PDAC were divided into two groups
      after neoadjuvant chemoradiotherapy: those with portal vein (PV) invasion alone
      (n = 12), and those with invasion of both PV and SMA (n = 13). A tape for
      guidance was passed in a space ventral to the SMA and behind the pancreatic
      parenchyma, followed by resection of the pancreatic parenchyma with the splenic
      vein. Another tape was passed behind the nerve plexus lateral to the hepatic
      artery and the SMA ventral to the inferior vena cava and the nerve plexus was
      dissected, resulting in complete resection of the nerve plexus around the SMA.
      Pathological findings revealed that the rates of R0, R01 (a margin less than 1
      mm) and R1 were 58.3 %, 41.7 % and 0 % in PV group, and 53.8 %, 30.8 % and 15.4 %
      in PV/A group, respectively. The median survival time was 23.3 and 22.8 months in
      PV and PV/A groups, respectively. The plexus hanging maneuver for PDAC of the
      pancreatic head achieved complete resection of the retropancreatic nerve plexus
      around the SMA, helping to secure a negative surgical margin. 

PMID- 24664422
TI  - Endoscopic evaluation of dysplasia in ulcerative colitis.

PMID- 24664420
TI  - Direct T cell activation via CD40 ligand generates high avidity CD8+ T cells
      capable of breaking immunological tolerance for the control of tumors.
AB  - CD40 and CD40 ligand (CD40L) are costimulatory molecules that play a pivotal role
      in the proinflammatory immune response. Primarily expressed by activated CD4+ T
      cells, CD40L binds to CD40 on antigen presenting cells (APCs), thereby inducing
      APC activation. APCs, in turn, prime cytotoxic T lymphocytes (CTLs). Here, two
      tumor-associated antigen (TAA) animal models, p53-based and GP100-based, were
      utilized to examine the ability of CD40-CD40L to improve antigen-specific CTL
      mediated antitumor immune responses. Although p53 and GP100 are self-antigens
      that generate low affinity antigen-specific CD8+ T cells, studies have shown that
      their functional avidity can be improved with CD40L-expressing APCs. Therefore,
      in the current study, we immunized mice with a DNA construct encoding a TAA in
      conjunction with another construct encoding CD40L via intramuscular injection
      followed by electroporation. We observed a significant increase in the antigen
      specific CTL-mediated immune responses as well as the potent antitumor effects in
      both models. Antibody depletion experiments demonstrated that CD8+ T cells play a
      crucial role in eliciting antitumor effects in vaccinated mice. Furthermore, we
      showed that in vitro stimulation with irradiated tumor cells expressing both TAA
      and CD40L improved the functional avidity of antigen-specific CD8+ T cells. Thus,
      our data show that vaccination with TAA/CD40L DNA can induce potent antitumor
      effects against TAA-expressing tumors through the generation of better
      functioning antigen-specific CD8+ T cells. Our study serves as an important
      foundation for future clinical translation. 

PMID- 24664423
TI  - Intraoperative pancreatoscopy: a valuable tool for pancreatic surgeons?
AB  - Effective treatment of pancreatic pathology relies on both preoperative and
      intraoperative decision making. Traditionally, the use of preoperative imaging
      and endoscopic modalities, in combination with intraoperative findings and
      pathologic evaluation, has guided the surgeons to perform the correct operative
      procedure. We hypothesize that the intraoperative use of pancreatoscopy
      (fiberoptic endoscopy of the pancreatic duct) is a valuable adjunct in selected
      cases to facilitate the performance of the appropriate definitive surgical
      treatment. We queried our IRB-approved, prospectively maintained the pancreatic
      surgery database identifying the uses of intraoperative pancreatoscopy in all
      pancreatic resections at our institution from 2005-2012. Operative notes,
      pathology reports, and perioperative outcomes were evaluated. During the study
      period, 1,016 pancreatic resections were performed at our institution. Twenty
      three cases during this period included the use of intraoperative pancreatoscopy.
      Eighteen (78 %) of these operations were performed for presumed main duct
      intraductal papillary mucinous neoplasm. In five cases (22 %), the surgical
      resection was extended secondary to the intraoperative pancreatoscopy findings.
      Appropriate surgical treatment of the pancreatic lesions can be challenging in
      the face of preoperative imaging limitations. The selective use of intraoperative
      fiberoptic endoscopy to evaluate the pancreatic duct appears to help to enable
      the surgeon to better perform the appropriate resection and optimal treatment. 

PMID- 24664424
TI  - Immediate radical therapy or conservative treatments when meeting the Milan
      criteria for advanced HCC patients after successful TACE.
AB  - BACKGROUND AND AIMS: Many advanced hepatocellular carcinoma (HCC) cases can be
      successfully downstaged into the Milan criteria; however, immediate radical
      therapy cannot be applied to all such patients for various reasons. Of the
      patients who are not eligible for immediate radical therapy, some accept repeated
      downstaging therapies and some undergo persistent observation. The aim of the
      present study was to compare long-term survival between these two groups of
      patients. PATIENTS AND METHODS: Between August 2003 and October 2008, 156 HCC
      patients successfully received downstaging therapy resulting in compliance with
      the Milan criteria. Of those, 98 cases accepted radical therapies, including
      liver transplantation (LT), resection, or radiofrequency ablation (RFA) (group
      1), and 58 cases underwent repeated transcatheter arterial chemoembolization
      (TACE) or persistent observation (group 2). The baseline characteristics,
      demographic data, downstaging protocol, and information on long-term outcomes
      were collected and compared. RESULTS: No significant differences were observed in
      the patient demographic data, downstaging protocols, or tumor characteristics
      between the two groups. The 1-, 3-, and 5-year overall survival rates were 92.9,
      82.7, and 78.6 %, respectively, in group 1, whereas these rates were 82.8, 65.5,
      and 48.3 %, respectively, in group 2 (P = 0.046). Among the 58 patients in group
      2, the 1-, 3-, and 5-year overall survival rates were 92.3, 65.4, and 46.2 %,
      respectively, in the repeated TACE group, and 81.3, 65.6, and 50 %, respectively,
      in the persistent observation group (P = 0.783). CONCLUSION: Immediate radical
      therapy should be the first choice for advanced HCC patients who undergo
      successful TACE, and repeated TACE is unnecessary.

PMID- 24664426
TI  - Magnetic resonance imaging changes of intervertebral discs after kyphoplasty.
AB  - BACKGROUND: Minimal-invasive cement augmentation techniques gained popularity
      recently. Long-term studies, however, are still not available focusing on the
      effect of possible acceleration of intervertebral disc degeneration. MATERIALS
      AND METHODS: Fifteen patients (average age 67.1 +/- 6.9 years, range 58-77; 10
      female, 5 male) with acute or osteoporotic fractures were included in this study
      and MRI scans were performed before surgery and after a mean follow-up period of
      15.2 months (range 8-27 months). Out of these patients, seven were available for
      a long-term MRI scan after a mean of 94.3 months (range 84-96 months). Disc
      degeneration and injuries were graded according to published Pfirrmann and Oner
      scales. RESULTS: A total of 43 intervertebral discs with moderate initial
      degeneration were examined pre-operatively and at the first follow-up. Twenty
      were available for the long-term-follow-up. At the first follow-up, 3 (1.3 %)
      discs showed a degenerative progression of 1 grade compared to the pre-operative
      MRI. Only one injured and one uninjured disc (0.4 %) showed progressive
      degeneration of 1 grade in the long-term follow up. No intervertebral disc in
      between bisegmental cement augmentation showed acceleration of degenerative
      changes. CONCLUSION: Despite several limitations regarding patients' age and lack
      of performed perfusion MRI scans, this study suggests that vertebral cement
      augmentation through kyphoplasty has no significant influence on disc
      degeneration even after a long period. The absence of severe disc degeneration
      after vertebral augmentation supports further clinical trials, which should
      incorporate endplate perfusion studies for detailed information regarding disc
      perfusion.

PMID- 24664427
TI  - Lowest instrumented vertebrae selection for selective posterior fusion of
      moderate thoracolumbar/lumbar idiopathic scoliosis: lower-end vertebra or lower
      end vertebra+1?
AB  - PURPOSE: To determine fusion necessity to one level below lower-end vertebra
      (LEV+1) in selective posterior fusion of moderate thoracolumbar/lumbar (TL/L)
      idiopathic scoliosis. METHODS: A total of 37 patients with moderate TL/L
      idiopathic scoliosis (Cobb angle of TL/L curve between 30 degrees  and 60 degrees
      ) were identified and three patients with TL/L curve Cobb angle more than 60
      degrees  were excluded. And the follow-up period was at least 2 years. Lowest
      instrumented vertebra (LIV) was one level proximal to LEV in three patients, LEV
      in 22 patients and LEV+1 in 12 patients. The three patients with TL/L Cobb angle
      more than 60 degrees  were all fused to LEV+1. Clinical and various radiographic
      measurements were collected before surgery, post-surgery and during last follow
      up, and analytical comparisons were made between LIV = LEV patients and LIV =
      LEV+1 patients. RESULTS: No significant difference was observed regarding
      clinical and radiographic parameters between LEV group and LEV+1 group
      preoperatively except LIV disc angle and LIV translation. The correction rate of
      unfused thoracic curve and TL/L curve was 52.7 and 79.9 % in LEV group and 52.5
      and 83.7 % in LEV+1 group at the last follow-up, indicating no significant
      difference (P = 0.976 and P = 0.415, respectively). Coronal balance and sagittal
      alignments were also comparable between the two groups. LIV translation was
      slightly less in LEV+1 group (P = 0.028) at the last follow-up on the basis that
      LEV+1 was less translated than LEV preoperatively. CONCLUSIONS: Our analysis
      almost showed no benefit for fusing to LEV+1 in moderate TL/L idiopathic
      scoliosis patients undergoing posterior selective fusion with pedicle screws. For
      patients with TL/L Cobb angle more than 60 degrees , the distal fusion level
      probably needs to be LEV+1.

PMID- 24664425
TI  - ERADication of EDEM1 occurs by selective autophagy and requires deglycosylation
      by cytoplasmic peptide N-glycanase.
AB  - ER degradation-enhancing alpha-mannosidase-like 1 protein (EDEM1) is involved in
      the routing of misfolded glycoproteins for degradation in the cytoplasm.
      Previously, we reported that EDEM1 leaves the endoplasmic reticulum via non-COPII
      vesicles (Zuber et al. in Proc Natl Acad Sci USA 104:4407-4412, 2007) and becomes
      degraded by basal autophagy (Le Fourn et al. in Cell Mol Life Sci 66:1434-1445,
      2009). However, it is unknown which type of autophagy is involved. Likewise, how
      EDEM1 is targeted to autophagosomes remains elusive. We now show that EDEM1 is
      degraded by selective autophagy. It colocalizes with the selective autophagy
      cargo receptors p62/SQSTM1, neighbor of BRCA1 gene 1 (NBR1) and autophagy-linked
      FYVE (Alfy) protein, and becomes engulfed by autophagic isolation membranes. The
      interaction with p62/SQSTM1 and NBR1 is required for routing of EDEM1 to
      autophagosomes since it can be blocked by short inhibitory RNA knockdown of the
      cargo receptors. Furthermore, p62/SQSTM1 interacts only with deglycosylated EDEM1
      that is also ubiquitinated. The deglycosylation of EDEM1 occurs by the cytosolic
      peptide N-glycanase and is a prerequisite for interaction and aggregate formation
      with p62/SQSTM1 as demonstrated by the effect of peptide N-glycanase inhibitors
      on the formation of protein aggregates. Conversely, aggregation of p62/SQSTM1 and
      EDEM1 occurs independent of cytoplasmic histone deacetylase. These data provide
      novel insight into the mechanism of autophagic degradation of the ER-associated
      protein degradation (ERAD) component EDEM1 and disclose hitherto unknown
      parallels with the clearance of cytoplasmic aggregates of misfolded proteins by
      selective autophagy. 

PMID- 24664428
TI  - Disagreements in surgical planning still exist between spinal surgeons in
      adolescent idiopathic scoliosis: a multisurgeon assessment.
AB  - PURPOSE: Determining a surgical plan for the treatment of adolescent idiopathic
      scoliosis (AIS) can be challenging. Despite treatment recommendations and
      classification systems (such as the Lenke classification system) there is still
      no consensus on the optimal surgical plan for each curve type. The main objective
      of this study is to analyze the disagreements in surgical planning between spinal
      surgeons in AIS. METHODS: In a monthly meeting, four orthopaedic spine surgeons
      from different institutions analyzed a consecutive series of AIS patients. The
      differences in surgical plans were evaluated for each patient. The primary
      physician of the patient presented the case and specifically stated the Lenke
      type of the deformity in the presentation. We wanted to specifically document the
      disagreements between surgeons despite knowing the Lenke type of the deformity.
      RESULTS: One hundred consecutive AIS patients were reviewed over a 10-month
      period. There was a difference of at least one surgical plan from at least one
      surgeon in 31 of the cases; 30 of these disagreements in surgical planning were
      about fusion levels; 19 of these 30 disagreements were in only the upper
      instrumented vertebra (UIV), while seven were disagreements in only the lowest
      instrumented vertebra (LIV). In four cases, both the UIV and LIV levels varied.
      CONCLUSIONS: There was at least one difference in surgical planning in 31 of the
      100 cases (31 %). This shows that despite treatment algorithms and the Lenke
      classification system, disagreements in surgical planning still exist between
      spinal surgeons.

PMID- 24664429
TI  - Target direction rather than position determines oculomotor expectation in
      repeating sequences.
AB  - Saccadic latencies to targets appearing to the left and right of fixation in a
      repeating sequence are significantly increased when a target is presented out of
      sequence. Is this because the target is in the wrong position, the wrong
      direction, or both? To find out, we arranged for targets in a horizontal plane
      occasionally to appear with an unexpected eccentricity, though in the correct
      direction. This had no significant effect on latency, unlike what is observed
      when targets appeared in the unexpected direction. That subjects learnt sequences
      of directions rather than simply positions was further confirmed in an experiment
      where saccade direction was a repeating sequence, but eccentricity was
      randomised. Latency was elevated when a target was episodically presented in an
      unexpected direction. Latencies were also elevated when targets appeared in the
      correct hemifield but at an unexpected direction (35 degrees  polar angular
      displacement from the horizontal, a displacement roughly equivalent in collicular
      spacing to our unexpected eccentricity), although this elevation was of a smaller
      magnitude than when targets appeared in an unexpected direction along the
      horizontal. Finally, we confirmed that not all changes in the stimulus cause
      disruption: an unexpected change in the orientation or colour of the target did
      not alter latency. Our results show that in a repeating sequence, the oculomotor
      system is primarily concerned with predicting the direction of an upcoming eye
      movement rather than its position. This is consistent with models of oculomotor
      control developed for randomly appearing targets in which the direction and
      amplitude of saccades are programmed separately.

PMID- 24664430
TI  - Controversial role of gamma-glutamyl transferase activity in cisplatin
      nephrotoxicity.
AB  - Nephrotoxicity of chemotherapeutics is a major hindrance in the treatment of
      various tumors. Therefore, test systems that reflect mechanisms of human kidney
      toxicity are necessary, and to reduce animal testing cell culture based systems
      have to be developed. One cell type that is of specific interest in this regard
      are renal proximal tubular epithelial cells, as they reabsorb substances from
      human primary urine filtrates and thus are exposed to urinary excreted
      xenobiotics and are a major target of cisplatin toxicity. While animal studies
      using gamma glutamyl transferase (GGT) knock-out mice or GGT inhibitors show that
      GGT activity increases kidney toxicity of cisplatin, the use of various cell
      models gives contradictory results. We therefore used a cell panel of
      immortalized human renal proximal tubular epithelial (RPTECs) cell lines
      differing in GGT activity. Low GGT activity resulted in high cisplatin
      sensitivity, as observed in RPTEC-SV40 cells or after siRNA mediated knock-down
      of GGT in RPTEC/TERT1 cells that have high GGT activity. However, the addition of
      GGT did not rescue, but also increased cisplatin sensitivity and adding GGT
      inhibitor as well as substrate (glutathione) or product (cysteinyl-glycine) of
      GGT resulted in decreased sensitivity. While our data suggest that the use of
      cell panels are of value in toxicology and toxicogenomics, they also emphasize on
      the complex interplay of toxins with the intracellular and extracellular
      microenvironment. In addition, we hypothesize that especially epithelial barrier
      formation and polarity of RPTECs need to be considered in toxicity models to
      validly predict the in vivo situation.

PMID- 24664431
TI  - Comparison of UVA-induced ROS and sunscreen nanoparticle-generated ROS in human
      immune cells.
AB  - Oxidative damage to cells and tissues from free radicals induced by ultraviolet
      (UV) irradiation can be attenuated by sunscreen components, such as ZnO and TiO2
      nanoparticles (NPs). Although it is known that reactive oxygen species (ROS) are
      generated by cells upon exposure to ZnO and TiO2 NPs, it is unknown to what
      extent the amount generated is altered with UV co-exposure. As it is a critical
      component for determining the relative risk of these NPs when used in sunscreen
      formulations, we have investigated ROS generation by these NPs in human THP-1
      monocyte immune cells following UVA co-exposure. Whilst the applied UVA dose (6.7
      J cm(-2)) did not alter cell viability after 24 h, it induced significant ROS
      production - causing a 7-fold increase in intracellular peroxide and 3.3-fold
      increase in mitochondrial superoxide levels after 1 h. However, co-exposure to
      NPs and UVA generated the same or less ROS than with UVA exposure alone, with the
      exception of anatase TiO2, which showed significantly increased levels. These
      findings indicate that ROS generation from nanosunscreens is, in most cases, an
      insignificant contributor to the overall risk associated with oxidative stress
      from UVA exposure itself. 

PMID- 24664433
TI  - The IQGAP-related protein DGAP1 mediates signaling to the actin cytoskeleton as
      an effector and a sequestrator of Rac1 GTPases.
AB  - Proteins are typically categorized into protein families based on their domain
      organization. Yet, evolutionarily unrelated proteins can also be grouped together
      according to their common functional roles. Sequestering proteins constitute one
      such functional class, acting as macromolecular buffers and serving as an
      intracellular reservoir ready to release large quantities of bound proteins or
      other molecules upon appropriate stimulation. Another functional protein class
      comprises effector proteins, which constitute essential components of many
      intracellular signal transduction pathways. For instance, effectors of small GTP
      hydrolases are activated upon binding a GTP-bound GTPase and thereupon
      participate in downstream interactions. Here we describe a member of the IQGAP
      family of scaffolding proteins, DGAP1 from Dictyostelium, which unifies the roles
      of an effector and a sequestrator in regard to the small GTPase Rac1. Unlike
      classical effectors, which bind their activators transiently leading to short
      lived signaling complexes, interaction between DGAP1 and Rac1-GTP is stable and
      induces formation of a complex with actin-bundling proteins cortexillins at the
      back end of the cell. An oppositely localized Rac1 effector, the Scar/WAVE
      complex, promotes actin polymerization at the cell front. Competition between
      DGAP1 and Scar/WAVE for the common activator Rac1-GTP might provide the basis for
      the oscillatory re-polarization typically seen in randomly migrating
      Dictyostelium cells. We discuss the consequences of the dual roles exerted by
      DGAP1 and Rac1 in the regulation of cell motility and polarity, and propose that
      similar signaling mechanisms may be of general importance in regulating
      spatiotemporal dynamics of the actin cytoskeleton by small GTPases. 

PMID- 24664434
TI  - A longitudinal analysis of electronic cigarette use and smoking cessation.

PMID- 24664432
TI  - Comparative myogenesis in teleosts and mammals.
AB  - Skeletal myogenesis has been and is currently under extensive study in both
      mammals and teleosts, with the latter providing a good model for skeletal
      myogenesis because of their flexible and conserved genome. Parallel
      investigations of muscle studies using both these models have strongly
      accelerated the advances in the field. However, when transferring the knowledge
      from one model to the other, it is important to take into account both their
      similarities and differences. The main difficulties in comparing mammals and
      teleosts arise from their different temporal development. Conserved aspects can
      be seen for muscle developmental origin and segmentation, and for the presence of
      multiple myogenic waves. Among the divergences, many fish have an indeterminate
      growth capacity throughout their entire life span, which is absent in mammals,
      thus implying different post-natal growth mechanisms. This review covers the
      current state of the art on myogenesis, with a focus on the most conserved and
      divergent aspects between mammals and teleosts. 

PMID- 24664435
TI  - Upregulation of EHD2 after intracerebral hemorrhage in adult rats.
AB  - EHD2, a member of the Eps15 homology domain (EH domain) family, is important for
      protein interactions during vesicular trafficking. Previous studies have proved
      that EHD2 can regulate trafficking from the plasma membrane in the process of
      endocytosis. However, its function in central nervous system diseases is still
      with limited understanding. In this frame, we found that EHD2 expression was
      upregulated in the perihematomal caudate in adult rats after intracerebral
      hemorrhage (ICH). Double immunofluorescence staining revealed that EHD2 was
      colocalized with neurons and activated microglias after ICH. Besides, we detected
      that neuronal apoptosis markers (TUNEL and caspase-3), and microglial activation
      marker (CD68), also known as a marker of macrophage, were colocated with EHD2.
      The vitro study also indicated that EHD2 was linked with neuronal apoptosis and
      microglial phagocytosis. All our findings suggested that EHD2 might be involved
      in the pathophysiology of ICH. 

PMID- 24664436
TI  - Activation of the kynurenine pathway in the acute phase of stroke and its role in
      fatigue and depression following stroke.
AB  - Many stroke survivors suffer from poststroke fatigue (PSF) and poststroke
      depression (PSD), indicating the importance of increasing the base of knowledge
      about the mechanisms underlying these sequelae. The primary aim of this study was
      to determine whether activation of the kynurenine (KYN) pathway predicts
      subsequent fatigue or depression in acute ischemic stroke (AIS) patients. Acute
      serum levels of 5-hydroxytryptamine (5-HT), tryptophan (TRP) catabolites
      (TRYCATs), and competing amino acids, as well as subsequent fatigue and
      depression, were measured in 45 stroke patients. TRP index [=100 * TRP /
      (tyrosine + valine + phenylalanine + leucine + isoleucine)] was significantly
      lower in patients with a Fatigue Severity Scale (FSS) score of >=4 at 12 months
      than in those with an FSS score of <4 (p = 0.039). Furthermore, the serum level
      of kynurenic acid in the acute stroke phase was significantly higher in patients
      with an FSS of score >=4 at 18 months than in those with an FSS score of <4 (p =
      0.026). These findings indicate that stroke patients with PSF have a lower
      bioavailability of TRP for 5-HT synthesis in the brain in the acute stroke phase.
      However, they also appear to have greater neuroprotective potential in that
      phase. In contrast to PSF, no predictors of PSD were found. These findings
      together with those of previous studies suggest that the immune response and
      indoleamine 2,3-dioxygenase activation that follows AIS can predict PSF but not
      PSD.

PMID- 24664437
TI  - Ras homolog enriched in the brain is linked to retinal ganglion cell apoptosis
      after light injury in rats.
AB  - Ras homolog enriched in the brain (Rheb) is a small GTPase of the Ras family. It
      has been confirmed that Rheb activation not only regulates cell growth and
      migration but also induces neuron apoptosis after toxic stimuli. However, the
      function of Rheb in the retina is still not fully understood. To find out whether
      Rheb was involved in retinal neuron death, the expression profile of Rheb in
      light-damaged retinal ganglion cells (RGCs) of adult rats was investigated.
      Western blotting showed the expression of Rheb was significantly upregulated in
      the injured retina. Rheb was mainly detected in apoptotic RGCs by using double
      immunofluorescent staining. Active caspase-3 was upregulated and co-labeled with
      Rheb. Meanwhile, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) showed that Rheb-positive RGCs underwent apoptosis after light
      exposure, which suggested that Rheb might be relevant to RGC apoptosis following
      phototoxicity. Furthermore, Western blotting and immunofluorescence showed that
      the expression profiles of CyclinD1 and cyclin-dependent kinase 4 (CDK4) were
      parallel with that of Rheb in a time-space dependent manner. Based on this study,
      it is speculated that Rheb might play an important role in physiological and
      pathological process in light-induced retina damage, which might provide a
      potential therapeutic avenue of retinal degeneration. 

PMID- 24664439
TI  - Capsule commentary on Price-Haywood et al., comparative effectiveness of audit
      feedback versus additional physician communication training to improve cancer
      screening for patients with limited health literacy.

PMID- 24664440
TI  - Sugar cane makes the medicine go down.

PMID- 24664438
TI  - Variants of COL3A1 are associated with the risk of stroke recurrence and
      prognosis in the Chinese population: a prospective study.
AB  - Type III collagen plays an important role in activating platelets, forming
      thrombus, and maintaining the mechanical properties of arteries. This study aimed
      to test the hypothesis that genetic variants of COL3A1 (gene encoding type III
      collagen) contribute to recurrence and prognosis of stroke. We investigated the
      associations of three variants (rs2138533, rs11887092, and rs1800255) in the
      COL3A1 gene with stroke recurrence and prognosis in 1,544 patients with three
      subtypes of stroke: lacunar infarction (n = 442), atherothrombotic infarction (n
      = 670), and hemorrhage (n = 432). These associations were evaluated by Kaplan
      Meier analysis and Cox regression models. Patients were followed up for 4.5
      years. The A allele of rs1800255 in the COL3A1 gene coding region was
      significantly associated with a reduced risk of stroke recurrence in patients
      with lacunar infarction (adjusted hazard ratio [HR] 0.58, 95 % confidence
      interval [CI] 0.36-0.93, P = 0.024), but there was an increased risk of all-cause
      mortality of atherothrombotic patients (adjusted HR 1.43, 95 % CI 1.01-2.00, P =
      0.044). The TT genotype of rs2138533 showed a significantly increased risk of
      death caused by cardiovascular disease or stroke in lacunar infarct patients
      (adjusted HR 2.98, 95 % CI 1.27-6.98, P = 0.012), but there was a reduced risk of
      all-cause mortality for patients with intracerebral hemorrhage (adjusted HR 0.34,
      95 % CI 0.12-0.93, P = 0.036). The G allele of rs11887092 increased the risk of
      stroke recurrence in patients with atherothrombotic stroke (adjusted HR 1.59, 95
      % CI 1.04-2.44, P = 0.035). In conclusion, variants of COL3A1 might play a vital
      role in determining the risk of recurrence and prognosis after stroke. 

PMID- 24664441
TI  - Ethical challenges for accountable care organizations: a structured review.
AB  - BACKGROUND: Accountable care organizations (ACOs) are proliferating as a solution
      to the cost crisis in American health care, and already involve as many as 31
      million patients. ACOs hold clinicians, group practices, and in many
      circumstances hospitals financially accountable for reducing expenditures and
      improving their patients' health outcomes. The structure of health care affects
      the ethical issues arising in the practice of medicine; therefore, like all
      health care organizational structures, ACOs will experience ethical challenges.
      No framework exists to assist key ACO stakeholders in identifying or managing
      these challenges. METHODS: We conducted a structured review of the medical ACO
      literature using qualitative content analysis to inform identification of ethical
      challenges for ACOs. RESULTS: Our analysis found infrequent discussion of ethics
      as an explicit concern for ACOs. Nonetheless, we identified nine critical ethical
      challenges, often described in other terms, for ACO stakeholders. Leaders could
      face challenges regarding fair resource allocation (e.g., about fairly using
      ACOs' shared savings), protection of professionals' ethical obligations
      (especially related to the design of financial incentives), and development of
      fair decision processes (e.g., ensuring that beneficiary representatives on the
      ACO board truly represent the ACO's patients). Clinicians could perceive threats
      to their professional autonomy (e.g., through cost control measures), a sense of
      dual or conflicted responsibility to their patients and the ACO, or competition
      with other clinicians. For patients, critical ethical challenges will include
      protecting their autonomy, ensuring privacy and confidentiality, and effectively
      engaging them with the ACO. DISCUSSION: ACOs are not inherently more or less
      "ethical" than other health care payment models, such as fee-for-service or pure
      capitation. ACOs' nascent development and flexibility in design, however, present
      a time-sensitive opportunity to ensure their ethical operation, promote their
      success, and refine their design and implementation by identifying, managing, and
      conducting research into the ethical issues they might face.

PMID- 24664442
TI  - Capsule commentary on Singh et al., A qualitative evaluation of geographical
      localization of hospitalists: how unintended consequences may impact quality.

PMID- 24664443
TI  - Suicide prevention in primary care: optimistic humanism imagined and engineered.

PMID- 24664444
TI  - Electrochemical characteristics of nanostructured platinum electrodes--a cyclic
      voltammetry study.
AB  - Platinum surfaces play a decisive role in catalysis in sensors, fuel cells, solar
      cells and other applications like neuronal stimulation and recording. Technical
      advances in nanotechnology contributed tremendously to the progress in these
      fields. A fundamental understanding of the chemical and physical interactions
      between the nanostructured surfaces and electrolytes is essential, but was barely
      investigated up to now. In this article, we present a wet-chemical process for
      the deposition of nanostructures on polycrystalline platinum surfaces. The
      electrochemically active surface area was increased by a factor of over 1000
      times with respect to the geometrical surface. The influence of the
      nanostructures was examined in different acidic, alkaline, and neutral
      electrolytes. Comparing cyclic voltammograms of nanostructured and planar
      polycrystalline platinum revealed new insights into the microenvironment at the
      electrode-electrolyte interface. The characteristic features of the cyclic
      voltammograms were altered in their shape and strongly shifted with respect to
      the applied potential. In neutral buffered and unbuffered electrolytes the water
      window was expanded from 1.4 V to more than 2 V. The shifts were interpreted as
      local pH-changes and exhausted buffer capacity in direct proximity of the
      electrode surface due to the strong release and binding of protons, respectively.
      These polarized electrodes induce significant changes in the electrochemical
      potential of the electrolyte due to the high roughness of their surface. The
      electrochemical phenomena and the observed voltage shifts are crucial for the
      understanding of the basic mechanism at nanostructured electrodes and mandatory
      for designing fuel cells, sensors and many other devices. 

PMID- 24664445
TI  - Prevalence of irritable bowel syndrome and functional dyspepsia, overlapping
      symptoms, and associated factors in a general population of Bangladesh.
AB  - BACKGROUND: This community-based survey aimed to find out the prevalence of
      irritable bowel syndrome (IBS), functional dyspepsia (FD), overlapping symptoms,
      and associated factors for overlap. METHOD: By cluster sampling method, 3,000
      (1,523 male) randomly selected adult subjects in the Sylhet district of
      Bangladesh were interviewed by a questionnaire based on ROME III criteria.
      Multivariate logistic regression analyses were done to find out the factors for
      overlap with significance level set at <=0.05. RESULTS: The mean age of the study
      population was 33.9 +/- 16.4 years. Prevalence of IBS and FD and IBS-FD were 12.9
      % (n = 387), 8.3 % (n = 249), and 3.5 % (n = 105), respectively. Approximately
      27.1 % of IBS patients and 42.1 % of FD patients had overlapping IBS-FD. The odds
      ratio for IBS-FD overlap was 6.3 (95 % CI, 4.8-8.4). Mean age (p = 0.011) and
      epigastric pain (p = 0.002) were more in overlap patients than FD alone, whereas
      epigastric pain syndrome subtype (p < 0.009) was more prevalent in lone FD
      subjects. In the multivariate logistic analysis, early satiety (OR, 3.0; 95 % CI,
      1.2-7.5; p = 0.018) and epigastric pain (OR, 14.5; 95 % CI, 5.0-42.1; p = 0.000)
      in FD patients appeared as independent risk factors for overlap. Bloating (p =
      0.026), <3 stools per week (p = 0.050), abdominal pain reduced by defecation (p =
      0.002), abdominal pain severity score (p = 0.004), and overall symptom frequency
      score (p = 0.000) were more in overlap patients than IBS-alone patients. In IBS
      patients, bloating (OR, 3.6; CI, 2.0-6.5; p = 0.000) was found as potential
      symptom associated with IBS-FD overlap. CONCLUSION: FD was a less prevalent
      disorder than IBS in our community, and significant overlap existed between the
      two disorders. Early satiety, epigastric pain, and bloating were important
      factors associated with overlap.

PMID- 24664446
TI  - Four GH11 xylanases from the xylanolytic fungus Talaromyces versatilis act
      differently on (arabino)xylans.
AB  - The filamentous fungus Talaromyces versatilis produces a wide range of
      cellulolytic and hemicellulolytic enzymes such as xylanases. The recent
      accessibility to the T. versatilis genome allows identifying two new genes, xynE
      and xynF, encoding glycoside-hydrolases from family GH11. Both genes were cloned
      and expressed in the methylotrophic yeast Pichia pastoris in order to compare
      these new xylanases with two other GH11 xylanases from T. versatilis (XynB and
      XynC) that were previously reported. High-level expression of recombinant enzymes
      was obtained for the four enzymes that were purified to homogeneity. The XynB,
      XynC, XynE and XynF enzymes have molecular masses of 34, 22, 45 and 23 kDa, an
      optimal pH between 3.5 and 4.5 and an optimal temperature between 50  degrees C
      and 60  degrees C. Interestingly, XynF has shown the best thermal stability at 50
      degrees C for at least 180 min with a weak loss of activity. The four xylanases
      catalysed hydrolysis of low viscosity arabinoxylan (LVAX) with K m(app) between
      11.5 and 23.0 mg.mL(-1) and k cat/K m(app) 170 and 3,963 s(-1) mg(-1).mL. Further
      investigations on the rate and pattern of hydrolysis of the four enzymes on LVAX
      showed the predominant production of xylose, xylobiose and some (arabino)xylo
      oligosaccharides as end products. The initial rate data from the hydrolysis of
      short xylo-oligosaccharides indicated that the catalytic efficiency increased
      with increasing degree of polymerisation of oligomer up to 6, suggesting that the
      specificity region of XynE and XynF spans at least six xylose residues. Because
      of their attractive properties, T. versatilis xylanases might be considered for
      biotechnological applications.

PMID- 24664447
TI  - Characterization of Thermotoga maritima glycerol dehydrogenase for the enzymatic
      production of dihydroxyacetone.
AB  - NAD-dependent Thermotoga maritima glycerol dehydrogenase (TmGlyDH) converts
      glycerol into dihydroxyacetone (DHA), a valuable synthetic precursor and sunless
      tanning agent. In this work, recombinant TmGlyDH was characterized to determine
      if it can be used to catalyze DHA production. The pH optima for glycerol
      oxidation and DHA reduction at 50  degrees C were 7.9 and 6.0, respectively.
      Under the conditions tested, TmGlyDH had a linear Arrhenius plot up to 80 
      degrees C. TmGlyDH was more thermostable than other glycerol dehydrogenases,
      remaining over 50 % active after 7 h at 50  degrees C. TmGlyDH was active on
      racemic 1,2-propanediol and produced (R)-1,2-propanediol from hydroxyacetone with
      an enantiomeric excess above 99 %, suggesting that TmGlyDH can also be used for
      chiral synthesis. (R)-1,2-propanediol production from hydroxyacetone was
      demonstrated for the first time in a one-enzyme cycling reaction using glycerol
      as the second substrate. Negative cooperativity was observed with glycerol and
      DHA, but not with the cofactor. Apparent kinetic parameters for glycerol, DHA,
      and NAD(H) were determined over a broad pH range. TmGlyDH showed little activity
      with N(6)-carboxymethyl-NAD(+) (N(6)-CM-NAD), an NAD(+) analog modified for easy
      immobilization to amino groups, but the double mutation V44A/K157G increased
      catalytic efficiency with N(6)-CM-NAD(+) ten-fold. Finally, we showed for the
      first time that a GlyDH is active with immobilized N(6)-CM-NAD(+), suggesting
      that N(6)-CM-NAD(+) can be immobilized on an electrode to allow TmGlyDH activity
      in a system that reoxidizes the cofactor electrocatalytically. 

PMID- 24664448
TI  - Nanofiber-coated drug eluting stent for the stabilization of mast cells.
AB  - PURPOSE: The nanofiber-hydrogel blend containing nitric oxide (NO) donors and
      reactive oxygen species (ROS) scavengers (Edaravone: EDV) was explored as an
      advanced strategy for stabilization of Mast cells (MCs) to achieve efficient
      immune-suppressive effects. METHODS: Three types of nanofiber hydrogel composites
      (Bare-Nanofibers (BNF), Nanofiber-Hydrogels (NF-Gel) and Cross-linked Nanofiber
      Hydrogels (NF-Gel-X)), were evaluated. The degranulation rates of MCs were
      determined by measurement of the extracellular levels of hydrogen peroxide and
      the released amounts of beta-hexosaminidase from the activated-MCs (a-MCs). In
      addition, the effects of EDV on the selective scavenging of the oxygen radicals
      and prevention of peroxynitrite formation were evaluated. The roles of a-MCs in
      re-endothelialization and viability of coronary artery endothelial cells
      (hPCAECs) were defined using alamar blue and LDH assay, respectively. RESULTS:
      Each polymer matrix has unique morphological characteristics. The effects of EDV
      (~1.0 mM) on the production of NO were greatly influenced by the presence of
      superoxide or hydroxyl radicals. NF-G-X containing a mixture of EDV and S
      Nitroglutathione (GSNO) produced the highest level of NO under the oxidative
      stress conditions. GSNO alone or a mixture of GSNO and EDV significantly lowered
      the degranulation rate of a-MCs (GSNO only: 55.8 +/- 5.4%; GSNO with EDV: 50.6 +/
      0.6%), indicating that NO plays an integral role in degranulation of a-MCs.
      There were no significant biochemical evidences of cytotoxic effects of GSNO and
      EDV on the hPCAECs. CONCLUSIONS: Nanofibers containing a mixture of nitric oxide
      donors and ROS scavengers could be used as a promising strategy to stabilize MCs
      from the ROS-mediated immune responses.

PMID- 24664449
TI  - Quality of sexual life after total hip arthroplasty in male patients with
      osteonecrosis of femoral head.
AB  - BACKGROUND: Patients with osteonecrosis of the femoral head (ONFH) have a severe
      impact on their health status, functionality and quality of life. Sexual life is
      an important component of the quality of life and is still a frequently neglected
      domain in patients with ONFH. The aims of the study were to evaluate the
      influence of the disease and the total hip arthroplasty (THA) surgery on quality
      of sexual life (QSL) in these patients. METHODS: A prospective, self-controlled
      study was done. 247 patients of ONFH who underwent unilateral or bilateral THA
      were asked to complete a standardized QSL questionnaire, and the score of QSL was
      evaluated preoperatively and at first year follow-up of post-THA operation.
      RESULTS: The mean age of the patient was 46.8 (range 25-60) years. 194 cases
      (78.5%, 276 hips) were alcohol-induced ONFH. There is significant decrease (p =
      0.026) in sexual relationship impairment on the 0-8 scale from pre-THA (5.3 +/-
      0.7) to post-THA (2.3 +/- 0.4). There is no significant difference for effect on
      sexual function (p = 0.14) between pre-THA (2.3 +/- 0.4) and post-THA (1.8 +/-
      0.3). There is significant improvement (p = 0.018) in overall sexual satisfaction
      degree of patients on the 1-5 scale from pre-THA (2.7 +/- 0.2) to post-THA (4.7
      +/- 0.6), but no significant increase for sexual partner. CONCLUSION: ONFH has
      impaired relationships with partner and overall sexual satisfaction degree of the
      male patients; THA has improved significantly relationships with partner and
      overall sexual satisfaction degree of the male patients, but no effect on sexual
      function of the patients and overall sexual satisfaction degree of sexual
      partner.

PMID- 24664450
TI  - Return to activity following fasciotomy for chronic exertional compartment
      syndrome.
AB  - Diagnosis of chronic exertional compartment syndrome (CECS) is relatively rare
      but has been well documented in athletes. There are, however, few reports
      regarding return to athletic activity after surgery among elite-level athletes.
      We hypothesized that a majority of elite-level athletes would successfully return
      to their previous level of competition following fasciotomy for CECS. A
      retrospective chart review was performed to identify elite-level athletes
      (collegiate or professional sport participation) who underwent fasciotomy for
      CECS over a 3-year period. Data collected included sport or activity, treatment
      and surgical details, time away from sport/activity after surgery, and ability to
      return to prior level of activity. Six males and seven females were included in
      the analysis. Patient age ranged from 17 to 24 years with a mean of 19.7 years.
      Six patients underwent unilateral lower extremity compartment release, and seven
      underwent bilateral lower extremity compartment release. The anterior and lateral
      compartments alone were released in 11 patients (84.6%). Two patients (15.4%)
      underwent four-compartment releases. Eleven patients (84.6%) were able to return
      to their previous elite level of sport participation at a mean of 10.6 weeks
      following surgical fasciotomy. Patients who had four-compartment release had a
      more than 3.5 week average longer return to full sporting activities (p = 0.011).
      Fasciotomy is effective in allowing elite athletes with CECS to return to sport.

PMID- 24664451
TI  - Humeral resurfacing arthroplasty in combination with latissimus dorsi tendon
      transfer in patients with rotator cuff tear arthropathy and preserved
      subscapularis muscle function: preliminary report and short-term results.
AB  - PURPOSE: Humeral resurfacing arthroplasty represents an alternative option to
      hemiarthroplasty for treatment of cuff tear arthropathy (CTA), with the
      advantages as follows: suitability for relatively young and high-demand patients
      because of preservation of bone stock and no loss of length, less invasive
      surgery, shorter operation time, no risk of periprosthetic stem fractures, and
      revision surgery can be undertaken easily. In the current study, resurfacing
      arthroplasty in combination with latissimus dorsi tendon transfer for CTA was
      performed. Three hypotheses: first, humeral resurfacing arthroplasty in
      combination with latissimus dorsi tendon transfer would improve the overall
      functional outcome in patients with CTA. Second, this combination would improve
      humeral external rotation. Third, this combination would improve abduction and
      shoulder elevation. METHODS: Study was conducted as an observational case series.
      Fourteen patients (nine ? and five ?) having CTA were included. Follow-up was
      carried out at the end of the 28th month for all patients. Constant Score was
      used for follow-up evaluation. Dorso-axillary approach was used for latissimus
      dorsi tendon transfer and ventral deltopectoral approach for Copeland
      resurfacing. Tendons were fixed to the greater tuberosity with two anchors.
      RESULTS: The absolute Constant Score significantly improved from 34
      preoperatively to 69 postoperatively, relative Constant Score from 42 to 91%,
      elevation from 95 degrees  to 138 degrees , abduction from 88 degrees  to 147
      degrees , and external rotation from 16 degrees  to 22 degrees  (not
      significant). CONCLUSION: Humeral resurfacing arthroplasty in combination with
      latissimus dorsi tendon transfer in patients having CTA with preserved
      subscapularis function has satisfactory short-term functional clinical outcome.
      LEVEL OF EVIDENCE: IV.

PMID- 24664452
TI  - Elderly pelvic fractures: the incidence is increasing and patient demographics
      can be used to predict the outcome.
AB  - OBJECTIVES: To (1) to determine the incidence of elderly pelvic fractures over
      the last decade, (2) describe the epidemiology and outcome of patients with pubic
      rami fractures and compare these to those patients sustaining all other pelvic
      fractures, and (3) identify independent predictors of length of stay, return to
      domicile, and 1-year mortality for patients with pubic rami fractures. METHODS:
      We retrospectively identified 937 elderly patients (>=65 years) with pelvic
      fractures presenting to the study centre over a 15-year period. Patient
      demographics, mechanism of injury, and associated fractures were recorded for a
      defined 2-year period. Outcomes assessed were length of stay, return to original
      place of domicile, and 1-year mortality. RESULTS: The incidence increased from
      7.9 per 100,000 to 13.1 per 100,000. The majority were fragility fractures of the
      pubic rami (84%). Patients sustaining a pubic rami fracture were older, more
      likely to be female, less deprived and have sustained an isolated injury by a low
      energy mechanism. Patients sustaining a pubic rami fracture were less likely to
      return to their original place of domicile. Pre-injury independence and mobility,
      socioeconomic status, associated fractures, energy of injury, and male gender
      were independent predictors of length of stay, return to original place of
      domicile, and 1-year mortality. CONCLUSION: The incidence of elderly pelvic
      fractures is increasing, and fractures of the pubic ramus have different patient
      demographics compared to other pelvic fractures. Patient demographics could be
      used to predict: length of stay, return to domicile, and 1-year mortality after a
      pubic rami fracture. LEVEL OF EVIDENCE: Retrospective prognostic study, Level IV.

PMID- 24664453
TI  - Danish surgeons allow the most athletic activities after total hip and knee
      replacement.
AB  - BACKGROUND AND PURPOSE: Counselling patients for or against athletic activities
      after well performed total hip arthroplasty (THA) and total knee arthroplasty
      (TKA). Level of evidence is low, and the current international guidelines are
      based on North American expert opinions in 2001 and 2008. Could technical and
      operative development and social or cultural differences apply for different
      counselling? METHODS: All Danish experts in head of departments performing more
      than 100 THAs or TKAs per year, were invited to fill in a questionnaire regarding
      the most popular sport activities in the Danish 60-69 years old population
      RESULTS: Response rate was 74 and 89% for the TKA and THA departments,
      respectively. A pronounced variation between the departments was observed and
      compared to the latest published US recommendations in 2007, the present Danish
      recommendations are significantly more liberal. Athletic activities are now
      allowed by 87% of the Danish arthroplasty departments. Of these 55% allow for
      high-impact activities after THA compared to 21% in US in 2007 (p < 0.0001).
      Recommendations for TKA patients are less liberal. Only 38% of the departments
      allow for high-impact activities after TKA compared to the 55% after THA (p <
      0.0001). INTERPRETATION: Based on the pronounced variation between departments
      and the fact that a highly significant trend was observed over 5 years on an
      undocumented basis it was concluded that there is an imminent need for a higher
      scientific level on this issue-which hopefully can develop in a few years using
      PROMs in large scale follow-up studies.

PMID- 24664456
TI  - Updating and prospective validation of a prognostic model for high sickness
      absence.
AB  - OBJECTIVES: To further develop and validate a Dutch prognostic model for high
      sickness absence (SA). METHODS: Three-wave longitudinal cohort study of 2,059
      Norwegian nurses. The Dutch prognostic model was used to predict high SA among
      Norwegian nurses at wave 2. Subsequently, the model was updated by adding person
      related (age, gender, marital status, children at home, and coping strategies),
      health-related (BMI, physical activity, smoking, and caffeine and alcohol
      intake), and work-related (job satisfaction, job demands, decision latitude,
      social support at work, and both work-to-family and family-to-work spillover)
      variables. The updated model was then prospectively validated for predictions at
      wave 3. RESULTS: 1,557 (77 %) nurses had complete data at wave 2 and 1,342 (65 %)
      at wave 3. The risk of high SA was under-estimated by the Dutch model, but
      discrimination between high-risk and low-risk nurses was fair after re
      calibration to the Norwegian data. Gender, marital status, BMI, physical
      activity, smoking, alcohol intake, job satisfaction, job demands, decision
      latitude, support at the workplace, and work-to-family spillover were identified
      as potential predictors of high SA. However, these predictors did not improve the
      model's discriminative ability, which remained fair at wave 3. CONCLUSIONS: The
      prognostic model correctly identifies 73 % of Norwegian nurses at risk of high
      SA, although additional predictors are needed before the model can be used to
      screen working populations for risk of high SA.

PMID- 24664455
TI  - Work-family conflict, emotional exhaustion and performance-based self-esteem:
      reciprocal relationships.
AB  - OBJECTIVES: The three constructs of work-family conflict, emotional exhaustion
      and performance-based self-esteem are all related to tremendous negative
      consequences for the individual, the organization as well as for society. Even
      though there are studies that connect two of those constructs, the prospective
      relations between all three of them have not been studied yet. METHODS: We
      explored the prospective relations between the three constructs in a large
      Swedish data set representative of the Swedish workforce. Gender differences in
      the relations were investigated. Longitudinal data with a 2-year time lag were
      gathered from 3,387 working men and women who responded to the 2006 and 2008
      waves of the Swedish Longitudinal Occupational Survey of Health. Four different
      cross-lagged models were analysed. RESULTS: In the best fitting model, higher
      levels of work-family conflict at time 1 were associated with an increased level
      of performance-based self-esteem at time 2, but not with emotional exhaustion,
      after controlling for having children, gender, education and age. Also,
      relationships between emotional exhaustion at time 1 and work-family conflict and
      performance-based self-esteem at time 2 could be established. Furthermore,
      relationships between performance-based self-esteem time 1 and work-family
      conflict and emotional exhaustion time 2 were found. Multiple-group analysis did
      not show any differences in the relations of the tested constructs over time for
      either men or women. CONCLUSIONS: We conclude that the three constructs are
      interrelated and best understood through a reciprocal model. No differences were
      found between men and women.

PMID- 24664454
TI  - Novel mutations widen the phenotypic spectrum of slow skeletal/beta-cardiac
      myosin (MYH7) distal myopathy.
AB  - Laing early onset distal myopathy and myosin storage myopathy are caused by
      mutations of slow skeletal/beta-cardiac myosin heavy chain encoded by the gene
      MYH7, as is a common form of familial hypertrophic/dilated cardiomyopathy. The
      mechanisms by which different phenotypes are produced by mutations in MYH7, even
      in the same region of the gene, are not known. To explore the clinical spectrum
      and pathobiology, we screened the MYH7 gene in 88 patients from 21 previously
      unpublished families presenting with distal or generalized skeletal muscle
      weakness, with or without cardiac involvement. Twelve novel mutations have been
      identified in thirteen families. In one of these families, the father of the
      proband was found to be a mosaic for the MYH7 mutation. In eight cases, de novo
      mutation appeared to have occurred, which was proven in four. The presenting
      complaint was footdrop, sometimes leading to delayed walking or tripping, in
      members of 17 families (81%), with other presentations including cardiomyopathy
      in infancy, generalized floppiness, and scoliosis. Cardiac involvement as well as
      skeletal muscle weakness was identified in nine of 21 families. Spinal
      involvement such as scoliosis or rigidity was identified in 12 (57%). This report
      widens the clinical and pathological phenotypes, and the genetics of MYH7
      mutations leading to skeletal muscle diseases. 

PMID- 24664457
TI  - Association of adiponectin gene polymorphism 45TG with gestational diabetes
      mellitus diagnosed on the new IADPSG criteria, plasma adiponectin levels and
      adverse pregnancy outcomes.
AB  - The aim of this study was to identify the association of adiponectin gene single
      nucleotide polymorphism (SNP) 45TG with gestational diabetes mellitus (GDM)
      diagnosed on the new International Diabetes in Pregnancy Consensus Group (IADPSG)
      criteria, plasma adiponectin levels and adverse pregnancy outcomes in Han women
      of Nantong area in China. This cross-sectional study included 128 pregnant women
      with GDM (GDM group) and 140 pregnant women with normal glucose tolerance (NGT
      group) according to oral glucose tolerance test results based on the new IADPSG
      criteria. The GDM pregnant women were treated by diet control or diet control and
      insulin injection. All pregnant women attended antenatal cares and were recorded
      until delivery. Adiponectin gene was amplified through PCR, and SNP was detected
      using restriction enzyme SmaI. Plasma adiponectin levels were measured by ELISA.
      The G allele and TG+GG genotype were significantly more frequent than the T
      allele in the GDM group than in the NGT group (p < 0.05). Plasma adiponectin
      concentrations of TG+GG genotype carriers were significantly lower than those of
      TT genotype in both groups (p < 0.01). After adjustment for confounding factors,
      plasma adiponectin level remained significantly lower in pregnant women with
      TG+GG genotype than those with TT genotype (p < 0.05). Compared with the NGT
      group, the GDM group with glycemic control still had significantly higher
      incidences of macrosomia, neonatal hypoglycemia and asphyxia (p < 0.05). Further
      analysis revealed that the incidences of macrosomia and neonatal hypoglycemia
      were significantly higher in pregnant women with TG+GG genotype than those with
      TT genotype after adjustment for potential confounders in affecting pregnancy
      outcomes (p < 0.05). Even though pregnant women are diagnosed as GDM according to
      the new IADPSG criteria, the adiponectin SNP45 may be closely correlated with the
      prevalence of GDM in Han women of Nantong area in China, and the allele +45G in
      adiponectin gene might be associated with reduced plasma adiponectin levels and
      adverse pregnancy outcomes.

PMID- 24664458
TI  - The metalloproteinase ADAM17 and the epidermal growth factor receptor (EGFR)
      signaling drive the inflammatory epithelial response in Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disorder that
      particularly compromises the function of exocrine glands. The pathogenetic
      mechanisms of this autoimmune exocrinopathy have not been fully elucidated. Since
      increasing evidence actually suggests that the epidermal growth factor receptor
      (EGFR) pathway has a major impact on the inflammatory/immune reactions of the
      epithelial cells, in the apparent effort of enhancing innate immune defense while
      opposing overactivation of pro-inflammatory functions, the focus of the work
      presented here is clarify whether the EGFR-extracellular-signal-regulated kinase
      (ERK) pathway plays a role in the pro-inflammatory responses mounted by pSS
      salivary gland epithelial cells (SGEC). Investigations revealed that the EGFR
      mediated activation of the downstream effectors ERK1/2 in pSS SGEC appeared to
      require ADAM17-dependent release of the endogenous EGFR ligand amphiregulin and
      transactivation of the EGFR. Moreover, blockade of amphiregulin bioactivity using
      a neutralizing Ab significantly reduced EGFR transactivation and ERK1/2
      phosphorylation. In addition, pSS SGEC treated with the specific ADAM17 inhibitor
      TAPI-1 and with the EGFR inhibitor AG1478 exhibited deactivated AREG/EGFR/ERK
      signaling pathway and reduced pro-inflammatory cytokines released.

PMID- 24664459
TI  - Mouse organ coefficient and abnormal sperm rate analysis with exposure to tap
      water and source water in Nanjing reach of Yangtze River.
AB  - Organ coefficients (including kidney, testis, liver and spleen coefficient) and
      abnormal sperm rate were used in our study to reflect the exposure to the Yangzte
      River water. The concentrations of total dissolved metals and semi-volatile
      organic compounds in tap and source water were measured by ICP-OES and GC-MS,
      respectively. After mice were fed with purified water (CK), Nanjing tap water
      (NJT) and Nanjing source water (NJS) for 90 day, the individual and organs
      (including kidney, testis, liver and spleen) of each mouse were weighted. And
      abnormal sperm types (such as hook less, banana-like form, amorphous, folded and
      two tails) were determined by microscope. The results showed that significant
      differences of liver coefficient between experimental group (NJT, NJS) and
      control group (CK) were observed; furthermore liver coefficient is positive
      correlation with the concentrations of total dissolved metals. However, no
      significant differences of abnormal sperm rates between experimental group (NJT,
      NJS) and control group (CK) were noted. So liver coefficient might be more
      sensitive than other organ coefficients to reflect the exposure to tap water and
      source water, while abnormal sperm rate could not be used to reveal the exposure
      to them.

PMID- 24664461
TI  - New insight into the role of patients during medical appointments: a synthesis of
      three qualitative studies.
AB  - BACKGROUND: The complexity of the doctor-patient relationship requires in-depth
      research to enable a better understanding of the nature of the doctor's
      appointment. OBJECTIVE: To explore how patients can facilitate their medical
      appointments, and how they can be responsible for their relationship with their
      doctors. METHODS: A synthesis of our previous three qualitative studies of doctor
      patient relationships focussed on the consultations. The analysis involved three
      qualitative studies based on in-depth interviews with 94 patients of family
      doctors in Poland. RESULTS: A detailed analysis of these data allowed us to
      distinguish several different ways in which patients participate in medical
      consultation, namely: 1. facilitating the visit; 2. having an impact on both
      patient and doctor perception of satisfaction with the visit; and 3. showing
      concern for the doctor, understanding the doctor's situation and having empathy.
      CONCLUSION: This study concerning patient-doctor interactions shows that each
      participant can explicitly provide emotional support for the other, despite the
      evident asymmetry in the roles of doctor and patient. Patients can substantially
      contribute to the personalisation of their relationship with the doctor, which is
      often facilitated by the repetition and regularity of the interaction.

PMID- 24664460
TI  - Percutaneous mitral valve repair with the MitraClip system according to the
      predicted risk by the logistic EuroSCORE: preliminary results from the German
      Transcatheter Mitral Valve Interventions (TRAMI) Registry.
AB  - OBJECTIVE: To evaluate in-hospital and short-term outcomes of percutaneous mitral
      valve repair according to patients' logistic EuroSCORE (logEuroSCORE) in a
      multicenter registry BACKGROUND: The logEuroSCORE is an established tool to
      predict the risk of mortality during cardiac surgery. In high-risk patients
      percutaneous mitral valve repair with the MitraClip system represents a less
      invasive alternative METHODS: Data from 1002 patients, who underwent percutaneous
      mitral valve repair with the MitraClip system, were analyzed in the German
      Transcatheter Mitral Valve Interventions (TRAMI) Registry. A logEuroSCORE
      (mortality risk in %) >= 20 was considered high risk RESULTS: Of all patients,
      557 (55.6%) had a logEuroSCORE >= 20. Implantation of the MitraClip was
      successful in 95.5 % (942/986) patients. Moderate residual mitral valve
      regurgitation was more often detected in patients with a logEuroSCORE >= 20
      (23.8% vs. 17.1%, respectively, P < 0.05). In patients with a logEuroSCORE >= 20
      the procedural complication rate was 8.9% (vs. 6.4, n.s.) and the in-hospital
      MACCE rate 4.9% (vs. 1.4% P < 0.01). The in-hospital mortality rate in patients
      with a logEuroSCORE >= 20 and logEuroSCORE < 20 was 4.3 and 1.1%, respectively (P
      <= 0.01) CONCLUSION: Percutaneous mitral valve repair with the MitraClip system
      is feasible in patients with a logEuroSCORE >= 20 with similar procedural results
      compared to patients with lower predicted risk. Although mortality was four times
      higher than in patients with logEuroSCORE < 20, mortality in high risk patients
      was lower than predicted. In those with a logEuroSCORE >= 20, moderate residual
      mitral valve regurgitation was more frequent.

PMID- 24664462
TI  - The need for truly integrated environmental assessments.

PMID- 24664464
TI  - Developments affecting northern lakes: a littoral perspective.

PMID- 24664465
TI  - Environmental relevance: a necessary component of experimental design to answer
      the question, "so what?".

PMID- 24664466
TI  - Using terrestrial mammalian carnivores for global contaminant monitoring.

PMID- 24664467
TI  - Changes in environmental attitudes of industry: past motivation and future
      direction.

PMID- 24664468
TI  - Representation of women as authors of collaborative cancer clinical trials.

PMID- 24664469
TI  - Mod-seq: high-throughput sequencing for chemical probing of RNA structure.
AB  - The functions of RNA molecules are intimately linked to their ability to fold
      into complex secondary and tertiary structures. Thus, understanding how these
      molecules fold is essential to determining how they function. Current methods for
      investigating RNA structure often use small molecules, enzymes, or ions that
      cleave or modify the RNA in a solvent-accessible manner. While these methods have
      been invaluable to understanding RNA structure, they can be fairly labor
      intensive and often focus on short regions of single RNAs. Here we present a new
      method (Mod-seq) and data analysis pipeline (Mod-seeker) for assaying the
      structure of RNAs by high-throughput sequencing. This technique can be utilized
      both in vivo and in vitro, with any small molecule that modifies RNA and
      consequently impedes reverse transcriptase. As proof-of-principle, we used
      dimethyl sulfate (DMS) to probe the in vivo structure of total cellular RNAs in
      Saccharomyces cerevisiae. Mod-seq analysis simultaneously revealed secondary
      structural information for all four ribosomal RNAs and 32 additional noncoding
      RNAs. We further show that Mod-seq can be used to detect structural changes in
      5.8S and 25S rRNAs in the absence of ribosomal protein L26, correctly identifying
      its binding site on the ribosome. While this method is applicable to RNAs of any
      length, its high-throughput nature makes Mod-seq ideal for studying long RNAs and
      complex RNA mixtures. 

PMID- 24664470
TI  - A versatile assay for RNA-binding proteins in living cells.
AB  - RNA-binding proteins (RBPs) control RNA fate from synthesis to decay. Since their
      cellular expression levels frequently do not reflect their in vivo activity,
      methods are needed to assess the steady state RNA-binding activity of RBPs as
      well as their responses to stimuli. While electrophoresis mobility shift assays
      (EMSA) have been used for such determinations, their results serve at best as
      proxies for the RBP activities in living cells. Here, we describe a quantitative
      dual fluorescence method to analyze protein-mRNA interactions in vivo. Known or
      candidate RBPs are fused to fluorescent proteins (eGFP, YFP), expressed in cells,
      cross-linked in vivo to RNA by ultraviolet light irradiation, and
      immunoprecipitated, after lysis, with a single chain antibody fragment directed
      against eGFP (GFP-binding protein, GBP). Polyadenylated RNA-binding activity of
      fusion proteins is assessed by hybridization with an oligo(DT) probe coupled with
      a red fluorophore. Since UV light is directly applied to living cells, the assay
      can be used to monitor dynamic changes in RNA-binding activities in response to
      biological or pharmacological stimuli. Notably, immunoprecipitation and
      hybridization can also be performed with commercially available GBP-coupled 96
      well plates (GFP-multiTrap), allowing highly parallel RNA-binding measurements in
      a single experiment. Therefore, this method creates the possibility to conduct in
      vivo high-throughput RNA-binding assays. We believe that this fast and simple
      radioactivity-free method will find many useful applications in RNA biology. 

PMID- 24664471
TI  - Outfoxed by RBFOX1-a caution about ascertainment bias.
AB  - We report on two patients with intragenic deletions of RBFOX1 and one patient
      with an intragenic duplication of RBFOX1. These patients, by report, all had
      autism spectrum disorder and/or developmental delay and had strong family
      histories of these conditions. We initially hypothesized that RBFOX1 was another
      susceptibility locus for autism spectrum disorder or developmental delay.
      However, epidemiological evidence examining large numbers of individuals did not
      support this hypothesis and the data presented here suggests that RBFOX1
      intragenic copy number variants are not pathogenic. This contradicts previous
      reports that examined smaller numbers of patients and controls. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 24664472
TI  - Body mass index is positively associated with bone mineral density in US older
      adults.
AB  - Literature has been conflicting as to whether obesity is protective against
      osteoporosis. Understanding the relationship is particularly important in light
      of the increasing prevalence of obesity among older adults. Study results confirm
      a protective association between obesity and osteoporosis in a recent, nationally
      representative sample of US older adults. PURPOSE: Currently, the majority of US
      older adults are either overweight or obese. Evidence regarding the relationship
      between body composition measures and bone mass is conflicting, possibly because
      different measures of obesity reflect multiple mechanisms. Additionally, there
      are important age, gender, and racial differences in a risk of osteoporosis and
      fat mass composition. The objective of this study was to examine the association
      between body mass index (BMI) and bone mineral density (BMD) in a recent,
      nationally representative sample of US older adults as well as to see if this
      relationship differs by age, sex, and race. METHODS: Data for this study were
      obtained from the National Health and Nutrition Examination Survey (2005-2008)
      for adults ages 50 and older (n = 3,296). Linear regression models were used to
      predict BMD of the femoral neck (measured by dual-energy X-ray absorptiometry
      (DXA)) as a function of BMI (measured height and weight) and a range of study
      covariates. RESULTS: Every unit increase in BMI was associated with an increase
      of 0.0082 g/cm(2) in BMD (p < 0.001). Interaction terms for BMI and age (p =
      0.345), BMI and sex (p = 0.413), and BMI and race (p = 0.725) were not
      statistically significant. CONCLUSIONS: Study results confirm the positive
      association between BMI and BMD, and this relationship does not differ by age,
      sex, or race. A 10-unit increase in BMI (e.g., from normal BMI to obese) would
      result in moving an individual from an osteoporotic BMD level to a normal BMD
      level. Results demonstrate a protective, cross-sectional association between
      obesity and osteoporosis in a recent sample of US older adults.

PMID- 24664473
TI  - Positive regulation of rice RING E3 ligase OsHIR1 in arsenic and cadmium uptakes.
AB  - The metalloid arsenic (As) and the heavy metal cadmium (Cd) are ubiquitously
      found at low concentrations in the earth. High concentrations of these elements
      in the soil and crops are severely dangerous to human health. We attempted to
      retrieve the RING E3 ubiquitin ligase gene for regulating As and Cd uptakes via
      the ubiquitin 26S proteasome system. Semi-quantitative reverse transcription
      polymerase chain reaction was conducted for a total of 47 Oryza sativa RING
      finger protein (OsRFP) genes to assess their expression patterns when exposed to
      As and Cd treatments. We identified one gene Oryza sativa heavy metal induced
      RING E3 ligase 1 (OsHIR1), which was significantly upregulated with both
      treatments. A yeast hybrid screen and a bimolecular fluorescence complementation
      assay showed that OsHIR1 clearly interacts with 5 substrate proteins, including
      tonoplast intrinsic protein 4;1 (OsTIP4;1) in the plasma membrane. In addition,
      OsHIR1 strongly degraded the protein level of OsTIP4;1 via the ubiquitin 26S
      proteasome system. Heterogeneous overexpression of OsHIR1 in Arabidopsis
      exhibited As- and Cd-insensitive phenotypes and resulted in decreased As and Cd
      accumulation in the shoots and roots, relative to the control. Herein, we report
      the novel finding that the OsHIR1 E3 ligase positively regulates OsTIP4;1 related
      to As and Cd uptakes. 

PMID- 24664474
TI  - Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A
      case report.
AB  - Febrile neutropenia is an oncologic emergency that can result in serious
      consequences. Granulocyte colony stimulating factors (G-CSFs) are often used as
      prophylaxis for febrile neutropenia. Bone pain is the most notorious adverse
      effect caused by G-CSFs. Specifically, with pegfilgrastim (Neulasta((r))), the
      incidence of bone pain is higher in practice than was observed during clinical
      trials. Traditional analgesics, such as non-steroidal anti-inflammatory drugs
      (NSAIDs) and opioids, can be ineffective in severe pegfilgrastim-induced bone
      pain. With the high frequency of this adverse effect, it is clear that health
      practitioners need additional treatment options for patients who experience
      severe pegfilgrastim-induced bone pain. The mechanisms of bone pain secondary to
      G-CSFs are not fully known, but research has shown that histamine release is
      involved in the inflammatory process. There is scant previous clinical data on
      antihistamine use in the management of G-CSF-induced pain. We present the first
      case report in which loratadine prophylaxis completely alleviated NSAID-resistant
      severe pain secondary to pegfilgrastim. The result showed that loratadine may be
      a promising option for severe, resistant pegfilgrastim-induced bone pain. Further
      clinical studies are warranted and ongoing.

PMID- 24664475
TI  - Facing the challenges of new melanoma-targeted therapies: Treatment of severe
      fevers associated with dabrafenib/trametinib combination therapy.
AB  - With the emergence of new oral therapies for metastatic melanoma to the market,
      as well as ongoing pre-marketing trials and special access schemes, it is
      important to keep up to date with the side effect profiles of these medications.
      A common side effect associated with the BRAF inhibitor dabrafenib is severe
      fever symptoms such as pyrexia and rigors/chills; however, treatment options are
      limited. We report a patient who was debilitated by severe pyrexia and rigors
      caused by dabrafenib used in combination with trametinib to treat metastatic
      melanoma, who was treated with low-dose steroids. To our knowledge, the use of
      prednisolone for the treatment and prevention of further dabrafenib-associated
      pyrexia is not published; however, it is a low risk and low cost option that was
      very effective in this case. 

PMID- 24664476
TI  - An assessment of risk factors associated with ifosfamide-induced encephalopathy
      in a large academic cancer center.
AB  - PURPOSE: Ifosfamide-induced encephalopathy is a neurotoxic adverse effect of
      ifosfamide chemotherapy. The objective of this study was to determine the
      incidence of encephalopathy in patients with lymphoma and sarcoma receiving
      ifosfamide chemotherapy and assess for potential risk factors that influence the
      incidence of encephalopathy. METHODS: A retrospective study of sarcoma and
      lymphoma patients receiving ifosfamide chemotherapy was performed at the
      participating institutions. Enrollment began 1 July 2011 and continued
      chronologically backwards until 100 sarcoma and 100 lymphoma patients were
      enrolled. Identification of ifosfamide-induced encephalopathy events was
      performed by reviewing provider documentation of ifosfamide infusions. Logistic
      regression was employed to determine associations between risk factors and
      ifosfamide-induced encephalopathy events. RESULTS: Of the 200 patients enrolled,
      29 (14.5%) patients experienced encephalopathy. Ifosfamide-induced encephalopathy
      occurred more frequently in the sarcoma population than the lymphoma population
      (24 vs. 5 patients, p < 0.001). In addition to cancer type, prior use of
      cisplatin, concomitant opioids, and use of CYP2B6 inhibitors remained as
      significant variables in the multivariate model conferring a 12.47, 2.81, and
      5.17 increased odds of experiencing encephalopathy, respectively. The odds of
      experiencing encephalopathy were 9.0 and 1.37 times higher for a one-unit
      increase in serum creatinine and hemoglobin, respectively, and 0.15 times lower
      for a one-unit increase in albumin. CONCLUSIONS: This is the first study to
      demonstrate that patients with sarcoma experienced ifosfamide-induced
      encephalopathy more often than those with lymphoma. For all patients,
      predisposing factors for ifosfamide-induced encephalopathy included previous
      cisplatin exposure, concomitant opioids and CYP2B6 inhibitors. Laboratory values
      that increased ifosfamide-induced encephalopathy risk included low serum albumin,
      increased serum creatinine, and increased hemoglobin.

PMID- 24664477
TI  - Does gastric acid suppression affect sunitinib efficacy in patients with advanced
      or metastatic renal cell cancer?
AB  - INTRODUCTION: Renal cell cancer is a chemotherapy-insensitive cancer treated by
      vascular endothelial growth factor receptor antagonists. Recently, a question has
      arisen on whether there is an interaction between tyrosine kinase inhibitors,
      such as sunitinib, and acid suppressing agents. METHODS: A retrospective chart
      review was conducted for patients at two tertiary care centers who received
      sunitinib between 1 January 2006 and 31 March 2013. Using electronic systems and
      a province-wide electronic health records database, medication dispensing records
      were obtained. A univariate Cox's proportional hazard model determined if acid
      suppression had effects on progression-free survival and overall survival.
      RESULTS: Of 383 patient charts reviewed, 231 were included in the study. Patients
      on intermittent acid suppression, lost to follow-up or received sunitinib for
      less than one week were excluded from the study. The median age of the study
      population was 65. Patients who received no acid suppression (n = 186) had a
      median progression-free survival of 23.6 weeks (95% CI, 19.0-31.9 weeks) and
      patients who received continuous acid suppression (n = 45) had a median
      progression-free survival of 18.9 weeks (95% CI, 11.0-23.7 p = 0.04). A median
      overall survival of 62.4 weeks (95% CI, 42.0-82.7 weeks) was observed in the
      group with no acid suppression, while a median overall survival of 40.9 weeks
      (95% CI, 26.1-74.4 weeks) was observed in the continuous acid suppression group
      (p = 0.02). CONCLUSION: There was a significant difference in progression-free
      survival and overall survival between the acid suppressed and no acid suppression
      groups. Further research is required to confirm this potential interaction.

PMID- 24664478
TI  - Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report
      and review of literature.
AB  - Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal
      (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T
      cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally
      treated with induction chemotherapy followed by an autologous transplant. She
      developed relapsed disease 10 months later with leukemic involvement. She was re
      induced with nelarabine 1500 mg/m(2) on days 1, 3, and 5 with 1 dose of IT
      cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the
      time of treatment, she was on continuous renal replacement therapy due to
      sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a
      complete remission, and recovered her renal function. She received a second cycle
      of nelarabine without additional IT prophylaxis one month later. A week after
      this second cycle, she noted numbness in her lower extremities. Predominantly
      sensory, though also motor and autonomic, peripheral neuropathy started in her
      feet, ascended proximally to the mid-thoracic region, and eventually included her
      distal upper extremities. A magnetic resonance imaging (MRI) of her spine
      demonstrated changes from C2 to C6 consistent with subacute combined
      degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy
      stabilized and showed slight improvement and ultimately received an unrelated,
      reduced-intensity allogeneic transplant while in complete remission, but relapsed
      disease 10 weeks later. She is currently being treated with best supportive care.
      To our knowledge, this is the first published case report of severe neurotoxicity
      caused by nelarabine in a patient who received concurrent IT chemotherapy. 

PMID- 24664479
TI  - Cloning of intron-removed enolase gene and expression, purification, kinetic
      characterization of the enzyme from Theileria annulata.
AB  - Tropical theileriosis is a disease caused by infection with an apicomplexan
      parasite, Theileria annulata, and giving rise to huge economic losses. In recent
      years, parasite resistance has been reported against the most effective
      antitheilerial drug used for the treatment of this disease. This emphasizes the
      need for alternative methods of treatment. Enolase is a key glycolytic enzyme and
      can be selected as a macromolecular target of therapy of tropical theileriosis.
      In this study, an intron sequence present in T. annulata enolase gene was removed
      by PCR-directed mutagenesis, and the gene was first cloned into pGEM-T Easy
      vector and then subcloned into pLATE31 vector, and expressed in Escherichia coli
      cells. The enzyme was purified by affinity chromatography using Ni-NTA agarose
      column. Steady-state kinetic parameters of the enzyme were determined using
      GraFit 3.0. High quantities (~65 mg/l of culture) of pure recombinant T. annulata
      enolase have been obtained in a higly purified form (>95 %). Homodimer form of
      purified protein was determined from the molecular weights obtained from a single
      band on SDS-PAGE (48 kDa) and from size exclusion chromatography (93 kDa). Enzyme
      kinetic measurements using 2-PGA as substrate gave a specific activity of ~40
      U/mg, K m: 106 MUM, kcat: 37 s(-1), and k cat/K m: 3.5 * 10(5) M(-1) s(-1). These
      values have been determined for the first time from this parasite enzyme, and
      availability of large quantities of enolase enzyme will facilitate further
      kinetic and structural characterization toward design of new antitheilerial
      drugs.

PMID- 24664480
TI  - Severe metallosis following total knee arthroplasty: a case report and review of
      radiographic signs.
AB  - Metallosis is an uncommon complication following total knee arthroplasty that
      leads to osteolysis and implant loosening due to chronic inflammatory reaction.
      Abrasion between the metallic surfaces of the implant releases metallic debris
      that interacts with the periprosthetic soft tissues and causes chronic synovitis.
      Here we present a case of a 65-year-old man who had undergone total knee
      arthroplasty 10 years ago and developed implant loosening associated with severe
      metallosis and varus instability. Radiographs show the three typical signs of
      metallosis: metal-line sign, bubble sign, and cloud sign. This patient was
      subjected to revision surgery consisting of debridement and primary implant
      replacement by a hinged endoprosthesis. Knowledge of the typical radiographic and
      clinical findings of metallosis is important to rapidly diagnose this
      complication and avoid progressive joint destruction. 

PMID- 24664481
TI  - Stress injury of the rib in a swimmer.
AB  - Rib stress injuries are uncommonly reported but have been documented among
      athletes, most notably rowers. There have only been two prior case reports of rib
      stress injuries in swimmers, both of which were young females. Magnetic resonance
      (MR) imaging was either not obtained or the imaging characteristics were
      incompletely described. We present a case of an isolated third rib stress injury
      in a collegiate male swimmer diagnosed via MR imaging. We briefly discuss the
      possible etiologies for rib stress injuries, their MR appearance, as well as
      their treatment. 

PMID- 24664483
TI  - Bi2MoO6 nanobelts for crystal facet-enhanced photocatalysis.
AB  - gamma-Bi2MoO6 single-crystal nanobelts with dominant {010} facets exhibit facet
      enhanced photocatalytic property for the photodegradation of dye pollutants under
      visible light irradiation. The charge carriers are more efficiently separated on
      the low-index facets due to the exposure of more photoactive sites to the
      reacting substrates.

PMID- 24664484
TI  - Low-grade gliomas.
AB  - Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often
      arise in young, otherwise healthy patients and generally have an indolent course
      with longer-term survival in comparison with high-grade gliomas. Treatment
      options include observation, surgery, radiation, chemotherapy, or a combined
      approach, and management is individualized based on tumor location, histology,
      molecular profile, and patient characteristics. Moreover, in this type of brain
      tumor with a relatively good prognosis and prolonged survival, the potential
      benefits of treatment must be carefully weighed against potential treatment
      related risks. We review in this article current management strategies for LGG,
      including surgery, radiotherapy, and chemotherapy. In addition, the importance of
      profiling the genetic and molecular properties of LGGs in the development of
      targeted anticancer therapies is also reviewed. Finally, given the prevalence of
      these tumors in otherwise healthy young patients, the impact of treatment on
      neurocognitive function and quality of life is also evaluated. 

PMID- 24664485
TI  - Management of localized esophageal cancer in the older patient.
AB  - Most patients with gastroesophageal cancers are older than 65 years of age. The
      management of older patients poses challenges because they have multiple
      comorbidities and physiological changes associated with aging. Furthermore, data
      are limited on tolerance of cancer therapy and the use of combined-modality
      treatments in this patient population to guide their treatment. In this article,
      we focus on the management of older patients with localized esophageal cancer,
      highlighting the role of comprehensive geriatric assessment to identify and
      better tailor treatment approaches in this patient population. We review the
      literature and discuss the role of surgical resection and potential complications
      specific to an older patient. We review the rationale of combined-modality
      treatment and the potential benefits of a chemoradiotherapy-based approach in
      this patient population. 

PMID- 24664486
TI  - Implications of functional proteomics in breast cancer.
AB  - Breast cancer is one of the major public health problems of the Western world.
      Recent advances in genomics and gene expression-profiling approaches have
      enriched our understanding of this heterogeneous disease. However, progress in
      functional proteomics in breast cancer research has been relatively slow. Allied
      with genomics, the functional proteomics approach will be important in improving
      diagnosis through better classification of breast cancer and in predicting
      prognosis and response to different therapies, including chemotherapy, hormonal
      therapy, and targeted therapy. In this review, we will present functional
      proteomic approaches with a focus on the recent clinical implications of
      utilizing the reverse-phase protein array platform in breast cancer research. 

PMID- 24664487
TI  - Profiling cancer gene mutations in clinical formalin-fixed, paraffin-embedded
      colorectal tumor specimens using targeted next-generation sequencing.
AB  - PURPOSE: The success of precision oncology relies on accurate and sensitive
      molecular profiling. The Ion AmpliSeq Cancer Panel, a targeted enrichment method
      for next-generation sequencing (NGS) using the Ion Torrent platform, provides a
      fast, easy, and cost-effective sequencing workflow for detecting genomic
      "hotspot" regions that are frequently mutated in human cancer genes. Most
      recently, the U.K. has launched the AmpliSeq sequencing test in its National
      Health Service. This study aimed to evaluate the clinical application of the
      AmpliSeq methodology. METHODS: We used 10 ng of genomic DNA from formalin-fixed,
      paraffin-embedded human colorectal cancer (CRC) tumor specimens to sequence 46
      cancer genes using the AmpliSeq platform. In a validation study, we developed an
      orthogonal NGS-based resequencing approach (SimpliSeq) to assess the AmpliSeq
      variant calls. RESULTS: Validated mutational analyses revealed that AmpliSeq was
      effective in profiling gene mutations, and that the method correctly pinpointed
      "true-positive" gene mutations with variant frequency >5% and demonstrated high
      level molecular heterogeneity in CRC. However, AmpliSeq enrichment and NGS also
      produced several recurrent "false-positive" calls in clinically druggable
      oncogenes such as PIK3CA. CONCLUSION: AmpliSeq provided highly sensitive and
      quantitative mutation detection for most of the genes on its cancer panel using
      limited DNA quantities from formalin-fixed, paraffin-embedded samples. For those
      genes with recurrent "false-positive" variant calls, caution should be used in
      data interpretation, and orthogonal verification of mutations is recommended for
      clinical decision making.

PMID- 24664489
TI  - Engaging diverse populations about biospecimen donation for cancer research.
AB  - Clinical research increasingly relies upon the availability of appropriate
      genetic materials; however, the proportion of biospecimens from racial/ethnic
      minority patients and healthy controls are underrepresented, which preclude
      equitable research across all patient groups for cancer treatment. National
      Cancer Institute-funded Community Network Program Centers in California, Florida,
      and New York collaborated with local community partners to conduct three
      independent formative research studies with diverse (African American, Asian
      American, Hispanic, and White) participants to explore their knowledge,
      attitudes, and beliefs about biobanking, and their experiences with the donation
      of biospecimens. Our findings demonstrated similarities in overall low knowledge
      and understanding about the use of biospecimens for research. This was
      exacerbated for non-English speakers. Racial and ethnic groups differed with
      regard to a number of factors that are obstacles for participation, e.g.,
      continuing medical mistrust (African Americans), lack of benefit (Hispanics),
      apprehension about the physical toll of donating (Vietnamese), usage of
      biospecimen for research (Hmong and Chinese), and suspicion of exploitation by
      corporate entities (Whites). However, participants uniformly reported general
      interest and willingness to participate in biobanking for altruistic purposes,
      particularly to benefit future generations. This interest was framed with a
      strong admonition that donations should be accompanied by transparency about
      study sponsorship and ownership, distribution and use of biospecimens, and study
      information that fit participants' backgrounds and experiences. This cross
      cultural regional analysis offers significant insights into the similarities and
      variations in opinions and perceptions about biobanking and the collection of
      biospecimens for use in cancer research. 

PMID- 24664491
TI  - Strain-tunable superconducting field-effect transistor with an organic strongly
      correlated electron system.
AB  - A novel type of flexible organic field-effect transistor in which strain effects
      can be finely tuned continuously has been fabricated. In this novel device
      structure, electronic phases can be controlled both by "band-filling" and by
      "band-width" continuously. Finally, co-regulation of "band-filling" and "band
      width" in the strongly-correlated organic material realize field-induced
      emergence of superconducting fractions at low temperature. 

PMID- 24664490
TI  - Surgical treatment of giant liver hydatid cysts: comparison of cystojejunostomy
      and partial cystectomy.
AB  - PURPOSE: The aim of this study was to compare partial cystectomy and internal
      drainage of the cyst cavity with cystojejunostomy for the surgical treatment of
      giant hepatic hydatid cysts. METHODS: Patients who underwent any type of surgical
      treatment between March 2009 and May 2013 for giant hepatic hydatid cysts were
      retrospectively evaluated. The data collected included demographic variables,
      diagnostic methods, surgical procedures, morbidity and mortality rates. RESULTS:
      Twenty-eight patients who underwent surgery for giant hepatic hydatid cysts were
      included. There were 16 (57 %) female patients, with a mean age of 32.8 years.
      The diagnostic methods primarily included abdominal ultrasonography and computed
      tomography, which were performed in 62 % of the patients. The patients were
      divided into two groups with respect to the treatment modality: Group A (n = 13)
      treated with cystojejunostomy and Group B (n = 15) treated with partial
      cystectomy. The overall rate of cavity-related complications was 25 % in Group B,
      whereas none of the patients in Group A had a cavity-related complication during
      the follow-up period (p < 0.05). CONCLUSION: Cystojejunostomy is an effective and
      safe surgical approach for the treatment of giant hepatic hydatid cysts, with a
      lower rate of morbidity than partial cystectomy, and thus may be the surgical
      treatment of choice for giant hepatic hydatid cysts.

PMID- 24664492
TI  - Identification of a novel missense mutation of MAF in a Japanese family with
      congenital cataract by whole exome sequencing: a clinical report and review of
      literature.
AB  - Congenital cataracts are the most important cause of severe visual impairment in
      infants. Genetic factors contribute to the disease development and 29 genes are
      known to cause congenital cataracts. Identifying the genetic cause of congenital
      cataracts can be difficult because of genetic heterogeneity. V-maf avian
      musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic
      region/leucine zipper transcription factor that plays a key role as a regulator
      of embryonic lens fiber cell development. MAF mutations have been reported to
      cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other
      anterior segment dysgenesis. We report on six patients in a family who have
      congenital cataracts were identified MAF mutation by whole exome sequencing
      (WES). The heterozygous MAF mutation Q303L detected in the present family occurs
      in a well conserved glutamine residue at the basic region of the DNA-binding
      domain. All affected members showed congenital cataracts. Three of the six
      members showed microcornea and one showed iris coloboma. Congenital cataracts
      with MAF mutation exhibited phenotypically variable cataracts within the family.
      Review of the patients with MAF mutations supports the notion that congenital
      cataracts caused by MAF mutations could be accompanied by microcornea and/or iris
      coloboma. WES is a useful tool for detecting disease-causing mutations in
      patients with genetically heterogeneous conditions.

PMID- 24664493
TI  - The Pt-enriched PtNi alloy surface and its excellent catalytic performance in
      hydrolytic hydrogenation of cellulose.
AB  - Ni-based catalysts are currently a subject of intense research in the hydrolytic
      hydrogenation of cellulose. We previously reported that Ni/ZSM-5 catalyst gave
      high yield of hexitols. However, Ni-based catalysts suffered fast deactivation in
      hot-compressed water. In this follow-up study we designed highly active Ni-based
      bimetallic catalysts with excellent hydrothermal stability for the hydrolytic
      hydrogenation of microcrystalline cellulose. PtNi/ZSM-5 shows a 76.9 % yield of
      hexitols, which is the best obtained so far in the hydrolytic hydrogenation of
      microcrystalline cellulose over Ni-based catalysts. Furthermore, the yield of
      hexitols remained greater than 55 % after the catalyst was reused for 4 times.
      The results showed that PtNi nanoparticles were formed with a Pt-enriched alloy
      surface as confirmed by XRD, H2-TPR (temperature-programmed H2 reduction), XPS (X
      ray photoelectron spectroscopy), and H2-TPD (temperature-programmed H2
      desorption). The surface features of these nano-particles were characterized by
      CO-TPD (temperature-programmed CO desorption), CO-FTIR (CO adsorption FTIR
      spectroscopy), HRTEM (high resolution TEM), and O2-TPO (temperature programmed
      oxidation) and this special surface structure may be responsible for the high
      activity, selectivity, and stability in the hydrolytic hydrogenation of cellulose
      in hot-compressed water.

PMID- 24664494
TI  - Transcatheter closure of atrial septal defects in children and adolescents:
      single-center experience with the GORE(r) septal occluder.
AB  - OBJECTIVES: Device closure of atrial septal defects (ASD II) is an alternative to
      surgery. ASD morphology and intracardiac relationships may influence device
      selection. Biocompatibility, techniques for closing large or multiple defects,
      and the risk of erosion are main issues in children BACKGROUND: The GORE(r)
      Septal Occluder (GSO) is a non-self-centering device with a flat and conformable
      nitinol-frame covered with expanded polytetrafluoroethylene. We hereby evaluate
      our initial experience in children to demonstrate feasibility, efficacy, and
      safety. METHODS: Single-center retrospective intention-to-treat analysis of GSO
      procedures in children and adolescents with hemodynamically significant ASD. All
      procedures were conducted under general anesthesia, fluoroscopy and
      transesophageal echocardiography. All defects were sized using stop-flow
      technique. GSOs of 20-30 mm disc-diameter were implanted. RESULTS: GSO
      implantation was attempted in 45 with technical success in 41 patients, median
      age 6 (range 3-17) years, bodyweight 19 (12-95) kg. Median balloon-sized diameter
      was 13 (8-19) mm resulting in a GSO-to-ASD-ratio of 2 (1.7-2.5). Deficient retro
      aortic rims (<3 mm) were found in 12 patients, and 10 of these 12 defects could
      be closed. We observed no complications. Four extensive or multiple ASDs were not
      treated successfully with GSO. After retrieval, one was closed with a different
      device; three patients needed surgical therapy. The median follow-up of four
      (range 0.2-22) months was uneventful in all patients CONCLUSIONS: We found the
      GSO device closure of ASDs in children to be effective. However, our initial
      experience is limited to short- and mid-term-follow-up of a low number of
      patients.

PMID- 24664495
TI  - Odd-impact loading results in increased cortical area and moments of inertia in
      collegiate athletes.
AB  - PURPOSE: The purpose of this study was to investigate tibial changes in
      volumetric bone mineral density and geometry that take place in athletes from pre
      to post-season. METHODS: Female college athletes (n = 36) and ten controls
      recruited from the student population were included in the study. Participants
      had their left tibia scanned by pQCT at 4, 20, and 66 % of the overall length
      from the distal end before and after their competitive seasons. Subjects were
      divided into four groups: non-athlete (controls, n = 10), moderate-impact (cross
      country runners, n = 13), high-impact (volleyball and basketball, n = 11), and
      odd-impact (soccer, n = 12). RESULTS: Anterior-posterior and medial-lateral
      diameter increased at the 4 % site in control subjects. In the moderate-impact
      group, medial-lateral moment of inertia (MOI) increased by 1.2 +/- 1.8 (mean +/-
      SD) percent at the 20 % site. In high-impact group, anterior-posterior MOI
      increased by 1.6 +/- 2.0 percent at the 66 % site. In odd-impact group, cortical
      area (1.4 +/- 2.3 %) and cortical thickness (1.8 +/- 2.8 %) increased at the 20 %
      site increased, as did the polar MOI (1.8 +/- 2.2 %) at the 66 % site.
      CONCLUSIONS: Load-specific changes resulting in improved measures of bone
      strength take place in athletes during a competitive season. These changes may
      result in improved resistance to fractures and stress fractures.

PMID- 24664498
TI  - Holt-Oram syndrome with intermediate atrioventricular canal defect, and aortic
      coarctation: functional characterization of a de novo TBX5 mutation.
AB  - Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by
      upper limb defects and congenital heart defects (CHD), which are often simple
      septal and conduction defects, less frequently complex CHDs. We report on a 9
      year-old boy with clinical and radiologic features of HOS consisting of bilateral
      asymmetric hypoplastic thumbs, generalized brachydactyly, limited supination due
      to radioulnar synostosis, and sloping shoulders, and intermediate
      atrioventricular canal defect (AVCD) with aortic coarctation. A de novo,
      previously described mutation, (Arg279ter) was identified in the TBX5 gene.
      Molecular characterization of this mutation was carried out due to the atypical
      CHD. In order to investigate whether the mutated transcript of TBX5 was able to
      escape the post-transcriptional surveillance mechanism and to produce a truncated
      TBX5 protein, we analyzed the TBX5 transcript, and protein pattern in HOS, and WT
      cardiac tissues. Our results demonstrate that the mutant TBX5 transcript is
      cleared by the cellular mechanism of surveillance. This data provides some
      support for the hypothesis that a dominant negative mutation, which strongly
      impairs the WT allele, might be too hazardous to be maintained. The literature
      suggests that HOS is relatively common among syndromes associated with AVCD.

PMID- 24664497
TI  - Algorithm for fast monoexponential fitting based on Auto-Regression on Linear
      Operations (ARLO) of data.
AB  - PURPOSE: To develop a fast and accurate monoexponential fitting algorithm based
      on Auto-Regression on Linear Operations (ARLO) of data, and to validate its
      accuracy and computational speed by comparing it with the conventional Levenberg
      Marquardt (LM) and Log-Linear (LL) algorithms. METHODS: ARLO, LM, and LL
      performances for T2* mapping were evaluated in simulation and in vivo imaging of
      liver (n=15) and myocardial (n=1) iron overload patients and the brain (two
      healthy volunteers). RESULTS: In simulations, ARLO consistently delivered
      accuracy similar to LM and significantly superior to LL. In in vivo mapping of T2
      * values, ARLO showed excellent agreement with LM, while LL showed only limited
      agreements with ARLO and LM. Compared with LM and LL in the liver, ARLO was 125
      and 8 times faster using our Matlab implementations, and 156 and 13 times faster
      using our C++ implementations. In C++ implementations, ARLO reduced the online
      whole-brain processing time from 9 min 15 s of LM and 35 s of LL to 2.7 s,
      providing T2 * maps approximately in real time. CONCLUSION: Due to comparable
      accuracy and significantly higher speed, ARLO can be considered as a valid
      alternative to the conventional LM algorithm for online T2 * mapping.

PMID- 24664499
TI  - Predictors of reading in Urdu: does deep orthography have an impact?
AB  - The aim of this study was to establish the extent to which rapid automatized
      naming (RAN) and non-word repetition (NWR) tasks predict reading fluency and
      reading accuracy in Urdu. One hundred sixty (8-9 years) children attending two
      types of schools (Urdu and English medium schools) were distributed into two
      groups, a control and a reading disability group on the basis of teacher's
      report. The results confirmed the role of RAN in predicting reading fluency in
      both groups. The role of NWR as a predictor of accuracy was also confirmed,
      although the strength of the relationship was modulated by RAN in the reading
      disability group. There are no tests available to identify children with reading
      problems in Urdu. Our study supports the validity of NWR and RAN tasks for the
      purposes of screening for reading deficits. The performance results also confirm
      the original grouping based on teacher reports. The study further highlights the
      importance of medium of instruction and increased oral language input in learning
      to read.

PMID- 24664500
TI  - Well-defined iron complexes as efficient catalysts for "green" atom-transfer
      radical polymerization of styrene, methyl methacrylate, and butyl acrylate with
      low catalyst loadings and catalyst recycling.
AB  - Environmentally friendly iron(II) catalysts for atom-transfer radical
      polymerization (ATRP) were synthesized by careful selection of the nitrogen
      substituents of N,N,N-trialkylated-1,4,9-triazacyclononane (R3 TACN) ligands. Two
      types of structures were confirmed by crystallography: "[(R3 TACN)FeX2 ]"
      complexes with relatively small R groups have ionic and dinuclear structures
      including a [(R3 TACN)Fe(MU-X)3 Fe(R3 TACN)](+) moiety, whereas those with more
      bulky R groups are neutral and mononuclear. The twelve [(R3 TACN)FeX2 ]n
      complexes that were synthesized were subjected to bulk ATRP of styrene, methyl
      methacrylate (MMA), and butyl acrylate (BA). Among the iron complexes examined,
      [{(cyclopentyl)3 TACN}FeBr2 ] (4 b) was the best catalyst for the well-controlled
      ATRP of all three monomers. This species allowed easy catalyst separation and
      recycling, a lowering of the catalyst concentration needed for the reaction, and
      the absence of additional reducing reagents. The lowest catalyst loading was
      accomplished in the ATRP of MMA with 4 b (59 ppm of Fe based on the charged
      monomer). Catalyst recycling in ATRP with low catalyst loadings was also
      successful. The ATRP of styrene with 4 b (117 ppm Fe atom) was followed by
      precipitation from methanol to give polystyrene that contained residual iron
      below the calculated detection limit (0.28 ppm). Mechanisms that involve
      equilibria between the multinuclear and mononuclear species were also examined.

PMID- 24664501
TI  - Optoelectronics of organic nanofibers formed by co-assembly of porphyrin and
      perylenediimide.
AB  - Organic nanofibers are formed by simple ionic co-assembly of positively charged
      porphyrin (electron donor) and negatively charged perylenediimide (electron
      acceptor) derivatives in aqueous solution. Two kinds of electron transfer routes
      between electron donor and electron acceptor under light excitation in nanofibers
      are confirmed by DFT calculations and experimental data. 

PMID- 24664502
TI  - Interleukin 17A promotes pneumococcal clearance by recruiting neutrophils and
      inducing apoptosis through a p38 mitogen-activated protein kinase-dependent
      mechanism in acute otitis media.
AB  - Streptococcus pneumoniae is a Gram-positive and human-restricted pathogen
      colonizing the nasopharynx with an absence of clinical symptoms as well as a
      major pathogen causing otitis media (OM), one of the most common childhood
      infections. Upon bacterial infection, neutrophils are rapidly activated and
      recruited to the infected site, acting as the frontline defender against emerging
      microbial pathogens via different ways. Evidence shows that interleukin 17A (IL
      17A), a neutrophil-inducing factor, plays important roles in the immune responses
      in several diseases. However, its function in response to S. pneumoniae OM
      remains unclear. In this study, the function of IL-17A in response to S.
      pneumoniae OM was examined using an in vivo model. We developed a model of acute
      OM (AOM) in C57BL/6 mice and found that neutrophils were the dominant immune
      cells that infiltrated to the middle ear cavity (MEC) and contributed to
      bacterial clearance. Using IL-17A knockout (KO) mice, we found that IL-17A
      boosted neutrophil recruitment to the MEC and afterwards induced apoptosis, which
      was identified to be conducive to bacterial clearance. In addition, our
      observation suggested that the p38 mitogen-activated protein kinase (MAPK)
      signaling pathway was involved in the recruitment and apoptosis of neutrophils
      mediated by IL-17A. These data support the conclusion that IL-17A contributes to
      the host immune response against S. pneumoniae by promoting neutrophil
      recruitment and apoptosis through the p38 MAPK signaling pathway. 

PMID- 24664503
TI  - Clostridium difficile extracytoplasmic function sigma factor sigmaV regulates
      lysozyme resistance and is necessary for pathogenesis in the hamster model of
      infection.
AB  - Clostridium difficile is a clinically important pathogen and the most common
      cause of hospital-acquired infectious diarrhea. Expression of the C. difficile
      gene csfV, which encodes sigma(V), an extracytoplasmic function sigma factor, is
      induced by lysozyme, which damages the peptidoglycan of bacteria. Here we show
      that sigma(V) is required for lysozyme resistance in C. difficile. Using
      microarray analysis, we identified the C. difficile genes whose expression is
      dependent upon sigma(V) and is induced by lysozyme. Although the peptidoglycan of
      wild-type C. difficile is intrinsically highly deacetylated, we have found that
      exposure to lysozyme leads to additional peptidoglycan deacetylation. This
      lysozyme-induced deacetylation is dependent upon sigma(V). Expression of pdaV,
      which encodes a putative peptidoglycan deacetylase, was able to increase lysozyme
      resistance of a csfV mutant. The csfV mutant strain is severely attenuated
      compared to wild-type C. difficile in a hamster model of C. difficile-associated
      disease. We conclude that the sigma(V) signal transduction system, which senses
      the host innate immune defense enzyme lysozyme, is required for lysozyme
      resistance and is necessary during C. difficile infection. 

PMID- 24664504
TI  - Aerobactin mediates virulence and accounts for increased siderophore production
      under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella
      pneumoniae.
AB  - Hypervirulent (hypermucoviscous) Klebsiella pneumoniae (hvKP) strains are an
      emerging variant of "classical" K. pneumoniae (cKP) that cause organ and life
      threatening infection in healthy individuals. An understanding of hvKP-specific
      virulence mechanisms that enabled evolution from cKP is limited. Observations by
      our group and previously published molecular epidemiologic data led us to
      hypothesize that hvKP strains produced more siderophores than cKP strains and
      that this trait enhanced hvKP virulence. Quantitative analysis of 12 hvKP strains
      in iron-poor minimal medium or human ascites fluid showed a significant and
      distinguishing 6- to 10-fold increase in siderophore production compared to that
      for 14 cKP strains. Surprisingly, high-pressure liquid chromatography (HPLC)-mass
      spectrometry and characterization of the hvKP strains hvKP1, A1142, and A1365 and
      their isogenic aerobactin-deficient (DeltaiucA) derivatives established that
      aerobactin accounted for the overwhelming majority of increased siderophore
      production and that this was not due to gene copy number. Further, aerobactin was
      the primary factor in conditioned medium that enhanced the growth/survival of
      hvKP1 in human ascites fluid. Importantly the ex vivo growth/survival of hvKP1
      DeltaiucA was significantly less than that of hvKP1 in human ascites fluid, and
      the survival of outbred CD1 mice challenged subcutaneously or intraperitoneally
      with hvKP1 was significantly less than that of mice challenged with hvKP1
      DeltaiucA. The lowest subcutaneous and intraperitoneal challenge inocula of 3 *
      10(2) and 3.2 * 10(1) CFU, respectively, resulted in 100% mortality,
      demonstrating the virulence of hvKP1 and its ability to cause infection at a low
      dose. These data strongly support that aerobactin accounts for increased
      siderophore production in hvKP compared to cKP (a potential defining trait) and
      is an important virulence factor. 

PMID- 24664505
TI  - Modulation of vacuolar pH is required for replication of Edwardsiella ictaluri in
      channel catfish macrophages.
AB  - Previous in vitro work demonstrated that Edwardsiella ictaluri produces an acid
      activated urease that can modulate environmental pH through the production of
      ammonia from urea. Additional work revealed that expression of the E. ictaluri
      type III secretion system (T3SS) is upregulated by acidic pH. Both the urease and
      the T3SS were previously shown to be essential to intracellular replication. In
      this work, fluorescence microscopy with LysoTracker Red DND-99 (LTR) indicated
      that E. ictaluri-containing vacuoles (ECV) became acidified following ingestion
      by head kidney-derived macrophages (HKDM). In vivo ratiometric imaging
      demonstrated a lowered ECV pH, which fell to as low as pH 4 but subsequently
      increased to pH 6 or greater. Inhibition of vacuolar H(+)-ATPases by use of the
      specific inhibitor bafilomycin A1 abrogated both ECV acidification and
      intracellular replication in HKDM. Failure of an E. ictaluri urease knockout
      mutant to increase the ECV pH in the in vivo ratiometric assay suggests that
      ammonia produced by the urease reaction mediates the pH increase. Additionally,
      when the specific arginase inhibitor l-norvaline was used to treat E. ictaluri
      infected HKDM, the ECV failed to neutralize and E. ictaluri was unable to
      replicate. This indicates that the HKDM-encoded arginase enzyme produces the urea
      used by the E. ictaluri urease enzyme. Failure of the ECV to acidify would
      prevent both upregulation of the T3SS and activation of the urease enzyme, either
      of which would prevent E. ictaluri from replicating in HKDM. Failure of the ECV
      to neutralize would result in a vacuolar pH too low to support E. ictaluri
      replication. 

PMID- 24664506
TI  - DrsG from Streptococcus dysgalactiae subsp. equisimilis inhibits the
      antimicrobial peptide LL-37.
AB  - SIC and DRS are related proteins present in only 4 of the >200 Streptococcus
      pyogenes emm types. These proteins inhibit complement-mediated lysis and/or the
      activity of certain antimicrobial peptides (AMPs). A gene encoding a homologue of
      these proteins, herein called DrsG, has been identified in the related bacterium
      Streptococcus dysgalactiae subsp. equisimilis. Here we show that geographically
      dispersed isolates representing 14 of 50 emm types examined possess variants of
      drsG. However, not all isolates within the drsG-positive emm types possess the
      gene. Sequence comparisons also revealed a high degree of conservation in
      different S. dysgalactiae subsp. equisimilis emm types. To examine the biological
      activity of DrsG, recombinant versions of two major DrsG variants, DrsGS and
      DrsGL, were expressed and purified. Western blot analysis using antisera raised
      to these proteins demonstrated both variants to be expressed and secreted into
      culture supernatants. Unlike SIC, but similar to DRS, DrsG does not inhibit
      complement-mediated lysis. However, like both SIC and DRS, DrsG is a ligand of
      the cathelicidin LL-37 and is inhibitory to its bactericidal activity in in vitro
      assays. Conservation of prolines in the C-terminal region also suggests that
      these residues are important in the biology of this family of proteins. This is
      the first report demonstrating the activity of an AMP-inhibitory protein in S.
      dysgalactiae subsp. equisimilis and suggests that inhibition of AMP activity is
      the primary function of this family of proteins. The acquisition of the
      complement-inhibitory activity of SIC may reflect its continuing evolution. 

PMID- 24664507
TI  - RTX toxin plays a key role in Kingella kingae virulence in an infant rat model.
AB  - Kingella kingae is a human oral bacterium that can cause diseases of the skeletal
      system in children and infective endocarditis in children and adults. K. kingae
      produces a toxin of the RTX group, RtxA. To investigate the role of RtxA in
      disease pathogenesis in vivo, K. kingae strain PYKK081 and its isogenic RtxA
      deficient strain KKNB100 were tested for their virulence and pathological
      consequences upon intraperitoneal injections in 7-day-postnatal (PN 7) rats. At
      the doses above 8.0 * 10(6) cells/animal, PYKK081 was able to cause a fatal
      illness, resulting in rapid weight loss, bacteremia, and abdominal necrotic
      lesion formation. Significant histopathology was observed in thymus, spleen, and
      bone marrow. Strain KKNB100 was less toxic to animals. Neither weight loss,
      bacteremia, nor histopathological changes were evident. Animals injected with
      KKNB100 exhibited a significantly elevated circulating white blood cell (WBC)
      count, whereas animals injected with PYKK081 had a WBC count that resembled that
      of the uninfected control. This observation parallels the subtleties associated
      with clinical presentation of K. kingae disease in humans and suggests that the
      toxin contributes to WBC depletion. Thus, our results demonstrate that RtxA is a
      key K. kingae virulence factor. Furthermore, our findings suggest that the PN 7
      rat can serve as a useful model for understanding disease caused by K. kingae and
      for elucidating diagnostic parameters in human patients. 

PMID- 24664508
TI  - BEC, a novel enterotoxin of Clostridium perfringens found in human clinical
      isolates from acute gastroenteritis outbreaks.
AB  - Clostridium perfringens is a causative agent of food-borne gastroenteritis for
      which C. perfringens enterotoxin (CPE) has been considered an essential factor.
      Recently, we experienced two outbreaks of food-borne gastroenteritis in which non
      CPE producers of C. perfringens were strongly suspected to be the cause. Here, we
      report a novel enterotoxin produced by C. perfringens isolates, BEC (binary
      enterotoxin of C. perfringens). Culture supernatants of the C. perfringens
      strains showed fluid-accumulating activity in rabbit ileal loop and suckling
      mouse assays. Purification of the enterotoxic substance in the supernatants and
      high-throughput sequencing of genomic DNA of the strains revealed BEC, composed
      of BECa and BECb. BECa and BECb displayed limited amino acid sequence similarity
      to other binary toxin family members, such as the C. perfringens iota toxin. The
      becAB genes were located on 54.5-kb pCP13-like plasmids. Recombinant BECb (rBECb)
      alone had fluid-accumulating activity in the suckling mouse assay. Although rBECa
      alone did not show enterotoxic activity, rBECa enhanced the enterotoxicity of
      rBECb when simultaneously administered in suckling mice. The entertoxicity of the
      mutant in which the becB gene was disrupted was dramatically decreased compared
      to that of the parental strain. rBECa showed an ADP-ribosylating activity on
      purified actin. Although we have not directly evaluated whether BECb delivers
      BECa into cells, rounding of Vero cells occurred only when cells were treated
      with both rBECa and rBECb. These results suggest that BEC is a novel enterotoxin
      of C. perfringens distinct from CPE, and that BEC-producing C. perfringens
      strains can be causative agents of acute gastroenteritis in humans. Additionally,
      the presence of becAB on nearly identical plasmids in distinct lineages of C.
      perfringens isolates suggests the involvement of horizontal gene transfer in the
      acquisition of the toxin genes. 

PMID- 24664509
TI  - Early Changes by (18)Fluorodeoxyglucose positron emission tomography coregistered
      with computed tomography predict outcome after Mycobacterium tuberculosis
      infection in cynomolgus macaques.
AB  - Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop
      both active tuberculosis and latent infection similar to those of humans,
      providing an opportunity to study the clinically silent early events in
      infection. (18)Fluorodeoxyglucose radiotracer with positron emission tomography
      coregistered with computed tomography (FDG PET/CT) provides a noninvasive method
      to measure disease progression. We sought to determine temporal patterns of
      granuloma evolution that distinguished active-disease and latent outcomes.
      Macaques (n = 10) were infected with low-dose M. tuberculosis with FDG PET/CT
      performed during infection. At 24 weeks postinfection, animals were classified as
      having active disease (n = 3) or latent infection (n = 6), with one "percolator"
      monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size,
      mineralization, and distribution of lesions) were compared among active and
      latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were
      observed in animals that would later develop active disease than in those that
      would develop latent infection. Over time, new lesions developed in active
      disease animals but not in latent animals. Granulomas and mediastinal lymph nodes
      from active-disease but not latent animals consistently increased in metabolic
      activity at early time points. The presence of fewer lesions at 3 weeks and the
      lack of new lesion development in animals with latent infection suggest that
      innate and rapid adaptive responses are critical to preventing active
      tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of
      adaptive responses, especially in the airway, should be emphasized in newer
      vaccine strategies. 

PMID- 24664511
TI  - A fine-tuned interaction between trimeric autotransporter haemophilus surface
      fibrils and vitronectin leads to serum resistance and adherence to respiratory
      epithelial cells.
AB  - Haemophilus influenzae type b (Hib) escapes the host immune system by recruitment
      of the complement regulator vitronectin, which inhibits the formation of the
      membrane attack complex (MAC) by inhibiting C5b-C7 complex formation and C9
      polymerization. We reported previously that Hib acquires vitronectin at the
      surface by using Haemophilus surface fibrils (Hsf). Here we studied in detail the
      interaction between Hsf and vitronectin and its role in the inhibition of MAC
      formation and the invasion of lung epithelial cells. The vitronectin-binding
      region of Hsf was defined at the N-terminal region comprising Hsf amino acids 429
      to 652. Moreover, the Hsf recognition site on vitronectin consisted of the C
      terminal amino acids 352 to 374. H. influenzae was killed more rapidly in
      vitronectin-depleted serum than in normal human serum (NHS), and increased MAC
      deposition was observed at the surface of an Hsf-deficient H. influenzae mutant.
      In parallel, Hsf-expressing Escherichia coli selectively acquired vitronectin
      from serum, resulting in significant inhibition of the MAC. Moreover, when
      vitronectin was bound to Hsf, increased bacterial adherence and internalization
      into epithelial cells were observed. Taking our findings together, we have
      defined a fine-tuned protein-protein interaction between Hsf and vitronectin that
      may contribute to increased Hib virulence. 

PMID- 24664510
TI  - Borrelia burgdorferi RNA induces type I and III interferons via Toll-like
      receptor 7 and contributes to production of NF-kappaB-dependent cytokines.
AB  - Borrelia burgdorferi elicits a potent cytokine response through activation of
      multiple signaling receptors on innate immune cells. Spirochetal lipoproteins
      initiate expression of NF-kappaB-dependent cytokines primarily via TLR2, whereas
      type I interferon (IFN) production is induced through the endosomal receptors
      TLR7 and TLR9 in human dendritic cells and TLR8 in monocytes. We demonstrate that
      DNA and RNA are the B. burgdorferi components that initiate a type I IFN response
      by human peripheral blood mononuclear cells (PBMCs). IFN-alpha protein and
      transcripts for IRF7, MX1, and OAS1 were induced by endosomal delivery of B.
      burgdorferi DNA, RNA, or whole-cell lysate, but not by lysate that had been
      treated with DNase and RNase. Induction of IFN-alpha and IFN-lambda1, a type III
      IFN, by B. burgdorferi RNA or live spirochetes required TLR7-dependent signaling
      and correlated with significantly enhanced transcription and expression of IRF7
      but not IRF3. Induction of type I and type III IFNs by B. burgdorferi RNA could
      be completely abrogated by a TLR7 inhibitor, IRS661. In addition to type I and
      type III IFNs, B. burgdorferi RNA contributed to the production of the NF-kappaB
      dependent cytokines, IFN-gamma, interleukin-10 (IL-10), IL-1beta, IL-6, and tumor
      necrosis factor alpha (TNF-alpha), by human PBMCs. Collectively, these data
      indicate that TLR7-dependent recognition of RNA is pivotal for IFN-alpha and IFN
      lambda1 production by human PBMCs, and that RNA-initiated signaling contributes
      to full potentiation of the cytokine response generated during B. burgdorferi
      infection. 

PMID- 24664513
TI  - Prevalence of visual-functional mismatch regarding coronary artery stenosis in
      the CVIT-DEFER registry.
AB  - The fractional flow reserve (FFR) is considered to be a reliable index for the
      assessment of clinically relevant coronary artery stenosis. However, mismatch in
      assessing the severity of coronary stenosis between coronary angiography and the
      FFR has been pointed out. The cardiovascular intervention therapeutics (CVIT)
      DEFER registry is a prospective multicenter registry study that has enrolled
      3,228 consecutive patients among 3,804 patients with angiographically moderate
      coronary artery lesions in whom FFR analysis was clinically indicated. The
      demographic and angiographic parameters associated with an FFR <=0.8 were
      analyzed, and the incidence of discrepancy between the angiographic severity of
      coronary stenosis and the FFR was assessed. Based on the visual assessment, 1,609
      (42.9%) lesions were categorized as showing 50% stenosis, 1,882 lesions (50.2%)
      as 75% stenosis, and 257 lesions (6.9%) as 90% stenosis. Angiographic-FFR
      "mismatch," which was defined as visual stenosis >=75% with FFR >0.80, was found
      in 43.4% of lesions, while reverse angiographic mismatch (visual stenosis <75%
      with FFR <=0.8) was found in 23.2%. The independent predictors for "angiographic
      FFR mismatch" were the presence of percutaneous coronary intervention (PCI)
      history, one-vessel disease, non-left anterior descending artery (LAD) location,
      non-diffuse lesion, non-ostial lesion, and non-tandem lesion. Conversely,
      "reverse angiographic mismatch" was independently associated with the multivessel
      disease, LAD location, and diffuse lesion. The FFR is not only influenced by
      luminal stenosis but also by coronary artery morphology and the amount of
      jeopardized myocardium. Angiographic-FFR mismatch is frequent in patients with
      moderate coronary stenosis, which suggests the clinical importance of using
      physiological assessment to guide PCI.

PMID- 24664512
TI  - Effects of bariatric surgery on male obesity-associated secondary hypogonadism:
      comparison of laparoscopic gastric bypass with restrictive procedures.
AB  - Bariatric surgery results in the complete resolution of male obesity-associated
      secondary hypogonadism (MOSH) in many patients. However, the effects of different
      bariatric surgical procedures on male sexual hormone profiles and sexual
      dysfunction have not been compared to date. We compared the pre- and post
      operative (at least 6 months after initial surgery) sex hormone profiles of 20
      severely obese men submitted to laparoscopic gastric bypass (LGB) with 15 similar
      patients submitted to restrictive techniques (sleeve gastrectomy in 10 and
      adjustable gastric banding in 5). We calculated free testosterone (FT) levels
      from total testosterone (TT) and sex hormone binding globulin (SHBG)
      concentrations. Fasting glucose and insulin levels served for homeostatic model
      assessment of insulin resistance (HOMAIR). MOSH was present in 25 and 16 of the
      35 patients when considering TT and FT concentrations respectively, resolving
      after surgery in all but one of them. When considering all obese men as a whole,
      patients submitted to LGB or restrictive procedures did not differ in terms of
      excess weight loss, in the decrease of fasting glucose and insulin, HOMAIR and
      waist circumference, or in the increase of serum 25-hydroxyvitamin D, TT and FT
      levels. The improvement in TT correlated with the decrease in fasting glucose (r
      = -0.390, P = 0.021), insulin (r = -0.425, P = 0.015) and HOMAIR (r = -0.380, P =
      0.029), and with the increase in SHBG (r = 0.692, P < 0.001). The increase in FT
      correlated with the decrease in fasting glucose (r = -0.360, P = 0.034). LGB and
      restrictive techniques are equally effective in producing a remission of MOSH.

PMID- 24664514
TI  - Amyloid-beta aggregation with gold nanoparticles on brain lipid bilayer.
AB  - Understanding and manipulating amyloid-beta (Abeta) aggregation provide key
      knowledge and means for the diagnosis and cure of Alzheimer's disease (AD) and
      the applications of Abeta-based aggregation systems. Here, we studied the
      formation of various Abeta aggregate structures with gold nanoparticles (AuNPs)
      and brain total lipid extract-based supported lipid bilayer (brain SLB). The
      roles of AuNPs and brain SLB in forming Abeta aggregates were studied in real
      time, and the structural details of Abeta aggregates were monitored and analyzed
      with the dark-field imaging of plasmonic AuNPs that allows for long-term in situ
      imaging of Abeta aggregates with great structural details without further
      labeling. It was shown that the fluid brain SLB platform provides the binding
      sites for Abeta and drives the fast and efficient formation of Abeta aggregate
      structures and, importantly, large Abeta plaque structures (>15 MUm in diameter),
      a hallmark for AD, were formed without going through fibril structures when Abeta
      peptides were co-incubated with AuNPs on the brain SLB. The dark-field scattering
      and circular dichroism-correlation data suggest that AuNPs were heavily involved
      with Abeta aggregation on the brain SLB and less alpha-helix, less beta-sheet and
      more random coil structures were found in large plaque-like Abeta aggregates. 

PMID- 24664515
TI  - Overexpression of Aspergillus tubingensis faeA in protease-deficient Aspergillus
      niger enables ferulic acid production from plant material.
AB  - The production of ferulic acid esterase involved in the release of ferulic acid
      side groups from xylan was investigated in strains of Aspergillus tubingensis,
      Aspergillus carneus, Aspergillus niger and Rhizopus oryzae. The highest activity
      on triticale bran as sole carbon source was observed with the A. tubingensis T8.4
      strain, which produced a type A ferulic acid esterase active against methyl p
      coumarate, methyl ferulate and methyl sinapate. The activity of the A.
      tubingensis ferulic acid esterase (AtFAEA) was inhibited twofold by glucose and
      induced twofold in the presence of maize bran. An initial accumulation of
      endoglucanase was followed by the production of endoxylanase, suggesting a
      combined action with ferulic acid esterase on maize bran. A genomic copy of the
      A. tubingensis faeA gene was cloned and expressed in A. niger D15#26 under the
      control of the A. niger gpd promoter. The recombinant strain has reduced protease
      activity and does not acidify the media, therefore promoting high-level
      expression of recombinant enzymes. It produced 13.5 U/ml FAEA after 5 days on
      autoclaved maize bran as sole carbon source, which was threefold higher than for
      the A. tubingensis donor strain. The recombinant AtFAEA was able to extract 50 %
      of the available ferulic acid from non-pretreated maize bran, making this enzyme
      suitable for the biological production of ferulic acid from lignocellulosic plant
      material.

PMID- 24664517
TI  - Definition of culture conditions for Arxula adeninivorans, a rational basis for
      studying heterologous gene expression in this dimorphic yeast.
AB  - The yeast Arxula adeninivorans is considered to be a promising producer of
      recombinant proteins. However, growth characteristics are poorly investigated and
      no industrial process has been established yet. Though of vital interest for
      strain screening and production processes, rationally defined culture conditions
      remain to be developed. A cultivation system was evolved based on targeted
      sampling and mathematical analysis of rationally designed small-scale
      cultivations in shake flasks. The oxygen and carbon dioxide transfer rates were
      analyzed as conclusive online parameters. Oxygen limitation extended cultivation
      and led to ethanol formation in cultures supplied with glucose. Cultures were
      inhibited at pH-values below 2.8. The phosphorus demand was determined as 1.55 g
      phosphorus per 100 g cell dry weight. Synthetic SYN6 medium with 20 g glucose l(
      1) was optimized for cultivation in shake flasks by buffering at pH 6.4 with 140
      mmol MES l(-1). Optimized SYN6 medium and operating conditions provided non
      limited cultivations without by-product formation. A maximal specific growth rate
      of 0.32 h(-1) and short fermentations of 15 h were achieved. A pH optimum curve
      was derived from the oxygen transfer rates of differently buffered cultures,
      showing maximal growth between pH 2.8 and 6.5. Furthermore, it was shown that the
      applied medium and cultivation conditions were also suitable for non-limiting
      growth and product formation of a genetically modified A. adeninivorans strain
      expressing a heterologous phytase.

PMID- 24664518
TI  - Selective glycerol oxidation by electrocatalytic dehydrogenation.
AB  - This study demonstrates that an electrochemical dehydrogenation process can be
      used to oxidize glycerol to glyceraldehyde and glyceric acid even without using
      stoichiometric chemical oxidants. A glyceric acid selectivity of 87.0 % at 91.8 %
      glycerol conversion was obtained in an electrocatalytic batch reactor. A
      continuous-flow electrocatalytic reactor had over an 80 % high glyceric acid
      selectivity at 10 % glycerol conversion, as well as greater reaction rates than
      either an electrocatalytic or a conventional catalytic batch reactor.

PMID- 24664516
TI  - Development of a phenotypic assay for characterisation of ethanologenic yeast
      strain sensitivity to inhibitors released from lignocellulosic feedstocks.
AB  - Inhibitors released by the breakdown of plant cell walls prevent efficient
      conversion of sugar into ethanol. The aim of this study was to develop a fast and
      reliable inhibitor sensitivity assay for ethanologenic yeast strains. The assay
      comprised bespoke 96-well plates containing inhibitors in isolation or
      combination in a format that was compatible with the Phenotypic Microarray
      Omnilog reader (Biolog, hayward, CA, USA). A redox reporter within the assay
      permits analysis of inhibitor sensitivity in aerobic and/or anaerobic conditions.
      Results from the assay were verified using growth on spot plates and tolerance
      assays in which maintenance of viability was assessed. The assay allows for
      individual and synergistic effects of inhibitors to be determined. It was
      observed that the presence of both acetic and formic acid significantly inhibited
      the yeast strains assessed, although this impact could be partially mitigated by
      buffering to neutral pH. Scheffersomyces stipitis, Candida spp., and Pichia
      guilliermondii demonstrated increased sensitivity to short chain weak acids at
      concentrations typically present in lignocellulosic hydrolysates. S. cerevisiae
      exhibited robustness to short chain weak acids at these concentrations. However,
      S. stipitis, Candida spp., and P. guilliermondii displayed increased tolerance to
      HMF when compared to that observed for S. cerevisiae. The results demonstrate
      that the phenotypic microarray assay developed in the current study is a valuable
      tool that can be used to identify yeast strains with desirable resistance to
      inhibitory compounds found in lignocellulosic hydrolysates. 

PMID- 24664519
TI  - Unsuspected pulmonary embolism in cancer patients: a narrative review with pooled
      data.
AB  - Detection of pulmonary embolism (PE) is not uncommon in patients undergoing
      computed tomography (CT) for routine staging of malignancy. Several studies have
      been conducted in recent years to evaluate the impact of unsuspected pulmonary
      embolism (UPE) on the prognosis and management of cancer patients. We aimed at
      summarizing the available evidence, to improve the understanding of the frequency
      and clinical significance of UPE in terms of survival, recurrent venous
      thromboembolism (VTE) and major bleeding. Medline was searched up to the end of
      September 2013, by using the terms "unsuspected pulmonary embolism" OR
      "incidental pulmonary embolism" OR "asymptomatic pulmonary embolism". We found
      552 out of 35,990 cancer patients diagnosed with UPE (14 studies), for a mean
      weighted prevalence of 1.82 % (95 % CI 1.47-2.21). When comparing cancer patients
      diagnosed with UPE to those presenting with symptomatic PE, we found a pooled OR
      of 0.96 (95 % CI 0.58-1.57) for mortality (3 studies), 0.87 (95 % CI 0.47-1.60)
      for recurrent VTE (4 studies) and 0.90 (95 % CI 0.43-1.88) for major bleeding (4
      studies). In conclusion, UPE represents a non-infrequent finding on CT scans
      ordered for reasons other than suspected PE and is a challenging clinical
      situation in the management of cancer patients. Even if UPE is generally milder
      in the short term, it may share a similar impact on survival and recurrent VTE,
      as compared to symptomatic PE. Large collaborative projects and, hopefully,
      interventional trials are needed to clarify the best management strategies. 

PMID- 24664520
TI  - Gut microbiota modulation: probiotics, antibiotics or fecal microbiota
      transplantation?
AB  - Gut microbiota is known to have a relevant role in our health, and is also
      related to both gastrointestinal and extradigestive diseases. Therefore,
      restoring the alteration of gut microbiota represents an outstanding clinical
      target for the treatment of gut microbiota-related diseases. The modulation of
      gut microbiota is perhaps an ancestral, innate concept for human beings. At this
      time, the restoration of gut microbiota impairment is a well-established concept
      in mainstream medicine, and several therapeutic approaches have been developed in
      this regard. Antibiotics, prebiotics and probiotics are the best known and
      commercially available options to overcome gastrointestinal dysbiosis. Fecal
      microbiota transplantation is an old procedure that has recently become popular
      again. It has shown a clear effectiveness in the treatment of C. difficile
      infection, and now represents a cutting-edge option for the restoration of gut
      microbiota. Nevertheless, such weapons should be used with caution. Antibiotics
      can indeed harm and alter gut microbiota composition. Probiotics, instead, are
      not at all the same thing, and thinking in terms of different strains is probably
      the only way to improve clinical outcomes. Moreover, fecal microbiota
      transplantation has shown promising results, but stronger proofs are needed.
      Considerable efforts are needed to increase our knowledge in the field of gut
      microbiota, especially with regard to the future use in its modulation for
      therapeutic purposes. 

PMID- 24664521
TI  - Interleukin-23 mediates the intestinal response to microbial beta-1,3-glucan and
      the development of spondyloarthritis pathology in SKG mice.
AB  - OBJECTIVE: Spondyloarthritides (SpA) occur in 1% of the population and include
      ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD),
      with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies
      implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and
      IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by
      entheseal-resident T cells. However, in genetically prone individuals, it is not
      clear where IL-23 is produced and how it drives the SpA syndrome, including IBD
      or subclinical gut inflammation of AS. Moreover, it is unclear why specific
      tissue involvement varies between patients with SpA. We undertook this study to
      determine the location of IL-23 production and its role in SpA pathogenesis in
      BALB/c ZAP-70(W163C)-mutant (SKG) mice injected intraperitoneally with beta-1,3
      glucan (curdlan). METHODS: Eight weeks after curdlan injection in wild-type or IL
      17A(-/-) SKG or BALB/c mice, pathology was scored in tissue sections. Mice were
      treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic
      reticulum (ER) stress were determined in affected organs. RESULTS: In curdlan
      treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent.
      Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in
      the ileum, where it amplified ER stress, goblet cell dysfunction, and
      proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was
      protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina
      propria mononuclear cells of ileitis-resistant BALB/c mice, which developed
      ileitis after curdlan injection and anti-IL-22. CONCLUSION: In response to
      systemic beta-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation
      and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent
      enthesitis. Innate IL-22 production promotes ileal tolerance.

PMID- 24664522
TI  - S-Nitrosylation in Alzheimer's disease.
AB  - S-Nitrosylation, a redox-mediated posttranslational modification, is a result of
      the covalent binding nitric oxide (NO)-related species to cysteine residues of
      target proteins with the formation of nitrosothiols (SNOs). Normally, protein S
      nitrosylation could be a cellular signaling mechanism, as is often a reversible
      and selective process, akin to protein phosphorylation. Emerging evidences have
      certified that the occurrence of aberrant S-nitrosylation of protein reactions
      could lead to protein misfolding, mitochondrial fission, synaptic damage, or
      apoptosis, thus contributing to the pathogenesis of Alzheimer's disease (AD). In
      this review, we summarize the recent findings of key S-nitrosylated proteins
      which play crucial roles in the pathogenesis of AD and discuss how SNO proteins
      affect the progression of AD. In addition, it has been demonstrated that
      interference of S-nitrosylation could potentially protect from mitochondrial
      dysfunction, synaptic loss, or neuronal cell death in AD animal models. Hence, we
      also present the recent advances and challenges in targeting S-nitrosylated
      proteins for AD therapies.

PMID- 24664523
TI  - Cyanotoxin management and human health risk mitigation in recreational waters.
AB  - The occurrence and severity of harmful cyanobacterial or blue-green algal blooms
      (HABs) have increased in recent decades, posing a serious threat of illness to
      humans. In some countries, water contaminated with cyanotoxins that is used for
      drinking or haemodialysis has posed a particularly serious risk. However, it is
      now recognized that recreational exposure to natural toxins by skin contact,
      accidental swallowing of water or inhalation can also cause a wide range of acute
      or chronic illnesses. In this review, we focus on the importance of cyanotoxin
      management in recreational waters. The symptoms related with HAB poisonings, the
      recommended safety concentrations limit for cyanobacteria and cyanotoxins in such
      waters, as well as early health hazard indicators of their presence and their
      monitoring are all discussed. We also present in this review an overview of the
      methods developed in recent decades for eliminating cyanobacteria and the toxic
      compounds that they produce. 

PMID- 24664524
TI  - Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based
      case-control study.
AB  - Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent
      literatures. Population-based replicate studies would cause false positive
      results due to population stratification. 229 recruit IS patients and their 229
      non-IS siblings were used in this study to avoid population stratification. The
      family-based study was conducted in Beijing from June 2005 to June 2012.
      Association between SNPs and IS was found in the sibship discordant tests, and
      the conditional logistic regression was performed to identify effect size and
      explore gene-environment interactions. Significant allelic association was
      identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C eta gene
      rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold
      risk (95% CI 1.04-3.46; P = 0.043) of IS, and it conferred susceptibility to IS
      only in a dominant model (OR 2.69; 95% CI 1.06-6.78; P = 0.036]. Risk of IS was
      higher (HR 3.58; 95% CI 1.54-8.31; P = 0.003) especially when the carriers of
      rs11833579 AA genotype were smokers. The present study suggests A allele of
      rs11833579 may play a role in mediating susceptibility to IS and it may increase
      the risk of IS together with smoking.

PMID- 24664525
TI  - Validating concepts of mental disorder: precedents from the history of science.
AB  - A fundamental issue in any branch of the natural sciences is validating the basic
      concepts for use in that branch. In psychiatry, this issue has not yet been
      resolved, and indeed, the proper nature of the problem has scarcely been
      recognised. As a result, psychiatry (or at least those parts of the discipline
      which aspire to scientific status) still cannot claim to be a part of scientific
      medicine, or to be incorporated within the common language of the natural
      sciences. While this creates difficulties within the discipline, and its standing
      in relation to other branches of medicine, it makes it an exciting place for
      "frontiersmen" (and women). This is one of the key growing points in the natural
      science tradition. In this essay, which moves from the early history of that
      tradition to today's debates in scientific psychiatry, I give my views about how
      these fundamental issues can move towards resolution.

PMID- 24664526
TI  - Habit learning and brain-machine interfaces (BMI): a tribute to Valentino
      Braitenberg's "Vehicles".
AB  - Brain-Machine Interfaces (BMI) allow manipulation of external devices and
      computers directly with brain activity without involvement of overt motor
      actions. The neurophysiological principles of such robotic brain devices and BMIs
      follow Hebbian learning rules as described and realized by Valentino Braitenberg
      in his book "Vehicles," in the concept of a "thought pump" residing in
      subcortical basal ganglia structures. We describe here the application of BMIs
      for brain communication in totally locked-in patients and argue that the thought
      pump may extinguish-at least partially-in those people because of extinction of
      instrumentally learned cognitive responses and brain responses. We show that
      Pavlovian semantic conditioning may allow brain communication even in the
      completely paralyzed who does not show response-effect contingencies. Principles
      of skill learning and habit acquisition as formulated by Braitenberg are the
      building blocks of BMIs and neuroprostheses.

PMID- 24664527
TI  - Quantifying iron-oxide nanoparticles at high concentration based on longitudinal
      relaxation using a three-dimensional SWIFT Look-Locker sequence.
AB  - PURPOSE: Iron-oxide nanoparticles (IONPs) have proven utility as contrast agents
      in many MRI applications. Previous quantitative IONP mapping has been performed
      using mainly T2 * mapping methods. However, in applications requiring high IONP
      concentrations, such as magnetic nanoparticles based thermal therapies,
      conventional pulse sequences are unable to map T2 * because the signal decays too
      rapidly. In this article, sweep imaging with Fourier transformation (SWIFT)
      sequence is combined with the Look-Locker method to map T1 of IONPs in high
      concentrations. METHODS: T1 values of agar containing IONPs in different
      concentrations were measured with the SWIFT Look-Locker method and with inversion
      recovery spectroscopy. Precisions of Look-Locker and variable flip angle (VFA)
      methods were compared in simulations. RESULTS: The measured R1 (=1/T1 ) has a
      linear relationship with IONP concentration up to 53.6 mM of Fe. This
      concentration exceeds concentrations measured in previous work by almost an order
      of magnitude. Simulations show SWIFT Look-Locker method is also much less
      sensitive to B1 inhomogeneity than the VFA method. CONCLUSION: SWIFT Look-Locker
      can accurately measure T1 of IONP concentrations <=53.6 mM. By mapping T1 as a
      function of IONP concentration, IONP distribution maps might be used in the
      future to plan effective magnetic nanoparticle hyperthermia therapy.

PMID- 24664528
TI  - What is normal nasal airflow? A computational study of 22 healthy adults.
AB  - BACKGROUND: Nasal airflow is essential for the functioning of the human nose.
      Given individual variation in nasal anatomy, there is yet no consensus what
      constitutes normal nasal airflow patterns. We attempt to obtain such information
      that is essential to differentiate disease-related conditions. METHODS:
      Computational fluid dynamics (CFD) simulated nasal airflow in 22 healthy subjects
      during resting breathing. Streamline patterns, airflow distributions, velocity
      profiles, pressure, wall stress, turbulence, and vortical flow characteristics
      under quasi-steady state were analyzed. Patency ratings, acoustically measured
      minimum cross-sectional area (MCA), and rhinomanometric nasal resistance (NR)
      were examined for potential correlations with morphological and airflow-related
      variables. RESULTS: Common features across subjects included: >50% total pressure
      drop reached near the inferior turbinate head; wall shear stress, NR, turbulence
      energy, and vorticity were lower in the turbinate than in the nasal valve region.
      However, location of the major flow path and coronal velocity distributions
      varied greatly across individuals. Surprisingly, on average, more flow passed
      through the middle than the inferior meatus and correlated with better patency
      ratings (r = -0.65, p < 0.01). This middle flow percentage combined with peak
      postvestibule nasal heat loss and MCA accounted for >70% of the variance in
      subjective patency ratings and predicted patency categories with 86% success.
      Nasal index correlated with forming of the anterior dorsal vortex. Expected for
      resting breathing, the functional impact for local and total turbulence,
      vorticity, and helicity was limited. As validation, rhinomanometric NR
      significantly correlated with CFD simulations (r = 0.53, p < 0.01). CONCLUSION:
      Significant variations of nasal airflow found among healthy subjects; Key
      features may have clinically relevant applications.

PMID- 24664529
TI  - A CT-based Medina classification in coronary bifurcations: does the lumen
      assessment provide sufficient information?
AB  - AIMS: To evaluate the distribution of atherosclerosis at bifurcations with
      computed tomography coronary angiography (CTCA) and propose a novel CT-Medina
      classification for bifurcation lesions. METHODS: In 26 patients (age 55 +/- 10
      years, 81% male) imaged with CTCA, 39 bifurcations were studied. The bifurcations
      analysis included the proximal main vessel, the distal main vessel and the side
      branch (SB). Plaque contours were manually traced on CTCA; the lumen, vessel and
      plaque area were measured, as well as plaque burden (%). The carina cross
      sections were divided into four equal parts according to the expected wall shear
      stress (WSS) to assess circumferential plaque distribution. All the bifurcation
      lesions were classified using the Medina classification and a novel CT-Medina
      classification combining lumen narrowing and plaque burden >=70%. RESULTS:
      Presence of severe plaque (plaque burden >=70%) by CTCA was demonstrated in 12.8%
      (5/39) of the proximal segments, 15.4% (6/39) of the distal segments and 7.7%
      (3/39) of the SB segments. The thickest plaque was located more often in low WSS
      parts of the carina cross-sections, whereas the flow divider was rarely affected.
      Although in the majority of bifurcations plaque was present, based on the Medina
      classification 92% of the assessed bifurcations were identified as 0,0,0.
      Characterization of bifurcation lesions using the new CT-Medina classification
      provided additional information in seven cases (18%) compared to the Medina
      classification CONCLUSION: Atherosclerotic plaque is widely present in all
      bifurcation segments, even in the absence of coronary lumen stenosis. A CT-Medina
      classification combining lumen and plaque parameters is more informative than
      angiographic classification of bifurcation lesions and could potentially
      facilitate the decision-making on the treatment of these lesions.

PMID- 24664530
TI  - Directed axonal outgrowth using a propagating gradient of IGF-1.
AB  - The temporospatial regulation of axon outgrowth is useful for guiding de novo
      connectivity or re-connectivity of neurons in neurological injury or disease.
      Here we report the successful construction of a biocompatible guidance device, in
      which a linear propagation of IGF-1 gradient sequentially directs axon outgrowth.
      We observe the extensive in vitro axonal extension over 5 mm with a desired
      growth rate of ~ 1 mm/day.

PMID- 24664531
TI  - Exome analysis of connective tissue dysplasia: death and rebirth of clinical
      genetics?
AB  - Exome results are reported for two patients with connective tissue dysplasia, one
      refining a clinical diagnosis of Ehlers-Danlos to Marfan syndrome, the other
      suggesting arthrogryposis derived from maternofetal Stickler syndrome. Patient 1
      had mutations in transthyretin (TTR), fibrillin (FBN1), and a calcium channel
      (CACNA1A) gene suggesting diagnoses of transthyretin amyloidosis, Marfan
      syndrome, and familial hemiplegic migraines, respectively. Patient 2 presented
      with arthrogryposis that was correlated with his mother's habitus and arthritis
      once COL2A1 mutations suggestive of Stickler syndrome were defined. Although DNA
      results often defy prediction by the best of clinicians, these patients
      illustrate needs for ongoing clinical scholarship (e.g., to delineate guidelines
      for management of mutations like that for hyperekplexia in Patient 2) and for
      interpretation of polygenic change that is optimized by clinical
      genetic/syndromology experience (e.g., suggesting acetazolamide therapy for
      Patient 1 and explaining arthrogryposis in Patient 2).

PMID- 24664532
TI  - Exercise physiologists emerge as allied healthcare professionals in the era of
      non-communicable disease pandemics: a report from Australia, 2006-2012.
AB  - Exercise can be prescribed to prevent, manage, and treat many leading non
      communicable diseases (NCDs) and underlying risk factors. However, surprisingly,
      Australia is one of only a few countries where allied healthcare professionals
      with specialized university education and training in exercise prescription and
      delivery provide services within a government-run healthcare system (Medicare).
      This article presents data on Medicare-funded services provided by accredited
      exercise physiologists (AEPs) from the inclusion of the profession in the allied
      healthcare model (January, 2006) to the end of 2012. We conceptualize these data
      in relation to current NCD trends, and outline recommendations that can
      potentially help curtail the current chronic disease burden through the further
      integration of exercise professionals into the healthcare system in Australia,
      and internationally. From 2006 to 2012, the number of AEPs in Australia has
      increased 563 %. This rise in AEPs has been paralleled by increased delivery of
      services for eligible patients with a chronic medical condition (+614 %), type 2
      diabetes mellitus (+211 to 230 %), and of Aboriginal and Torres Strait Islander
      descent (+343 %). These trends, which were developed through the "early years" of
      the profession, are encouraging and suggest that AEPs have taken up a vital
      position within the healthcare system. However, the total number of services
      provided by AEPs currently remains very low in relation to the prevalence of
      overweight-obesity and type 2 diabetes in Australia. Furthermore, services for
      Aboriginal Australians are very low considering the extreme burden of chronic
      diseases in these vulnerable populations. We provide some recommendations that
      may help the exercise physiology profession play a greater role in tackling the
      NCD burden and shift the healthcare model in a direction that is more proactive
      and focused on disease prevention and health, including the early identification
      and treatment of major upstream risk factors.

PMID- 24664533
TI  - Mutations in HADHB, which encodes the beta-subunit of mitochondrial trifunctional
      protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy.
AB  - Mitochondrial trifunctional protein (MTP) is a hetero-octamer composed of four
      alpha- and four beta-subunits that catalyzes the final three steps of
      mitochondrial beta-oxidation of long chain fatty acids. HADHA and HADHB encode
      the alpha-subunit and the beta-subunit of MTP, respectively. To date, only two
      cases with MTP deficiency have been reported to be associated with
      hypoparathyroidism and peripheral polyneuropathy. Here, we report on two siblings
      with autosomal recessive infantile onset hypoparathyroidism, peripheral
      polyneuropathy, and rhabdomyolysis. Sequence analysis of HADHA and HADHB in both
      siblings shows that they were homozygous for a mutation in exon 14 of HADHB
      (c.1175C>T, [p.A392V]) and the parents were heterozygous for the mutation.
      Biochemical analysis revealed that the patients had MTP deficiency. Structural
      analysis indicated that the A392V mutation identified in this study and the N389D
      mutation previously reported to be associated with hypoparathyroidism are both
      located near the active site of MTP and affect the conformation of the beta
      subunit. Thus, the present patients are the second and third cases of MTP
      deficiency associated with missense HADHB mutation and infantile onset
      hypoparathyroidism. Since MTP deficiency is a treatable disease, MTP deficiency
      should be considered when patients have hypoparathyroidism as the initial
      presenting feature in infancy.

PMID- 24664534
TI  - Iron fluoride hollow porous microspheres: facile solution-phase synthesis and
      their application for Li-ion battery cathodes.
AB  - Iron fluoride cathodes have been attracting considerable interest due to their
      high electromotive force value of 2.7 V and their high theoretical capacity of
      237 mA h g(-1) (1 e(-) transfer). In this study, uniform iron fluoride hollow
      porous microspheres have been synthesized for the first time by using a facile
      and scalable solution-phase route. These uniform porous and hollow microspheres
      show a high specific capacity of 210 mA h g(-1) at 0.1 C, and excellent rate
      capability (100 mA h g(-1) at 1 C) between 1.7 and 4.5 V versus Li/Li(+) . When
      in the range of 1.3 to 4.5 V, stable capacity was achieved at 350 mA h g(-1) at a
      current of 50 mA g(-1) . 

PMID- 24664535
TI  - Bronchoscopic lung volume reduction with endobronchial valves for patients with
      heterogeneous emphysema and intact interlobar fissures (the BeLieVeR-HIFi trial):
      study design and rationale.
AB  - Although lung volume reduction surgery improves survival in selected patients
      with emphysema, there has been ongoing interest in developing and evaluating
      bronchoscopic approaches to try to reduce lung volumes with less morbidity and
      mortality. The placement of endobronchial valves is one such technique, and
      although some patients have had a significant improvement, responses have been
      inconsistent because collateral ventilation prevents lobar atelectasis. We
      describe the protocol of a trial (ISRCTN04761234) aimed to show that a responder
      phenotype, patients with heterogeneous emphysema and intact interlobar fissures
      on CT scanning, can be identified prospectively, leading to a consistent benefit
      in clinical practice. 

PMID- 24664537
TI  - Long-term cost-effectiveness analysis of endovascular versus open repair for
      abdominal aortic aneurysm based on four randomized clinical trials.
AB  - BACKGROUND: A number of published economic evaluations of elective endovascular
      aneurysm repair (EVAR) versus open repair for abdominal aortic aneurysm (AAA)
      have come to differing conclusions about whether EVAR is cost-effective. This
      paper reviews the current evidence base and presents up-to-date cost
      effectiveness analyses in the light of results of four randomized clinical
      trials: EVAR-1, DREAM, OVER and ACE. METHODS: Markov models were used to estimate
      lifetime costs from a UK perspective and quality-adjusted life-years (QALYs)
      based on the results of each of the four trials. The outcomes included in the
      model were: procedure costs, surveillance costs, reintervention costs, health
      related quality of life, aneurysm-related mortality and other-cause mortality.
      Alternative scenarios about complications, reinterventions and deaths beyond the
      trial were explored. RESULTS: Models based on the results of the EVAR-1, DREAM or
      ACE trials did not find EVAR to be cost-effective at thresholds used in the UK
      (up to L30,000 per QALY). EVAR seemed cost-effective according to models based on
      the OVER trial. These results seemed robust to alternative model scenarios about
      events beyond the trial intervals. CONCLUSION: These analyses did not find that
      EVAR is cost-effective compared with open repair in the long term in trials
      conducted in European centres. EVAR did appear to be cost-effective based on the
      OVER trial, conducted in the USA. Caution must be exercised when transferring the
      results of economic evaluations from one country to another.

PMID- 24664538
TI  - Copy number alterations and neoplasia-specific mutations in MELK, PDCD1LG2, TLN1,
      and PAX5 at 9p in different neoplasias.
AB  - Genetic alterations affecting 9p are commonly present in many cancer types and
      many cancer-related genes are located in this chromosomal region. We sequenced
      all of the genes located in a 32Mb region of 9p by targeted next generation
      sequencing (NGS) in 96 patients with different cancer types, including acute
      lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated
      pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy
      number alterations (CNA), and mutations were studied from the NGS data. We
      detected a deletion at the CDKN2A locus as being the most frequent genetic
      alteration in all cancer types. In addition to this locus, NGS also identified
      other small regions of copy number loss and gain. However, different cancer types
      did not reveal any statistically significant differences with regard to CNA
      frequency or type. Of the 191 genes within the target region, two novel recurrent
      mutations were found in the MELK and PDCD1LG2 genes. The most commonly mutated
      gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and
      RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1,
      and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p
      region, in addition to commonly deleted CDKN2A locus, we were able to identify a
      number of small deletions and gains, as well as novel recurrent mutations in
      different cancer types. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24664540
TI  - Programmed degradation of DNA multilayer films.
AB  - The design and assembly of DNA multilayer films with programmable degradation
      properties are reported. The nanostructured DNA films are assembled through the
      layer-by-layer (LbL) assembly technique and can be programmed to degrade by
      subsequently introducing DNA strands of specific sequences. The strands
      preferentially hybridize to the building blocks that stabilize the film
      structure, causing the film to rearrange and degrade. The rate of degradation is
      influenced by both the availability and accessibility of the complementary DNA
      binding sites within the film, as well as the degree of crosslinking within the
      film. Similar results are obtained for DNA multilayer films assembled on planar
      and particle supports. This approach offers an avenue to tailor degradability
      features into DNA-based materials that may find application in the biosciences,
      in areas such as biosensing and drug delivery. 

PMID- 24664539
TI  - Tolerability of the capsaicin 8% patch following pretreatment with lidocaine or
      tramadol in patients with peripheral neuropathic pain: a multicentre, randomized,
      assessor-blinded study.
AB  - BACKGROUND: Application of the capsaicin 8% patch is associated with treatment
      related discomfort. Consequently, pretreatment for 60 min with anaesthetic cream
      is recommended; however, this may be uncomfortable and time consuming. METHODS:
      We conducted a multicentre, randomized (1:1), assessor-blinded study in patients
      with peripheral neuropathic pain to assess tolerability of the capsaicin patch
      following topical lidocaine (4%) or oral tramadol (50 mg) pretreatment. The
      primary endpoint was the proportion of patients tolerating capsaicin patch
      application (ability to receive >=90% of a 60-min application). Numeric Pain
      Rating Scale (NPRS) scores were assessed before, during and after treatment.
      RESULTS: Overall, 122 patients were included (61 per arm). The capsaicin patch
      was tolerated by 121 patients. Tolerability of the capsaicin patch was similar
      following pretreatment with lidocaine and tramadol. Following patch application,
      pain levels increased up to 55 min (change from baseline of 1.3 for lidocaine and
      1.4 for tramadol). After patch removal, tramadol-treated patients experienced
      greater pain relief up to the end of day 1; in the evening, mean changes in NPRS
      scores from baseline were 0 for lidocaine and -1 for tramadol. Proportions of
      patients reporting increases of >=2 NPRS points or >33% from baseline at one or
      more time point(s) on the day of treatment were similar between arms. Adverse
      event incidence was comparable between arms. CONCLUSIONS: Capsaicin 8% patch
      tolerability was similar in the two arms, with comparable results for most
      secondary endpoints. Tramadol given 30 min before patch application should be
      considered as an alternative pretreatment option in patients receiving capsaicin
      patch treatment.

PMID- 24664541
TI  - Nitrooleate mediates nitric oxide synthase activation in endothelial cells.
AB  - Nitrated lipids such as nitrooleate (OLA-NO2) can act as endogenous peroxisome
      proliferator-activated receptor gamma (PPARgamma) ligands to exert vascular
      protective effects. However, the molecular mechanisms regarding nitric oxide (NO)
      production and its regulation are not fully defined in the vasculature. Here, we
      show that OLA-NO2 increased endothelial NO release by modulating activation of
      endothelial nitric oxide synthase (eNOS) in endothelial cells. Treatment with OLA
      NO2 (3 MUM) increased NO release in a time-dependent manner. OLA-NO2 decreased
      protein expression of eNOS and caveolin-1 (Cav-1) but increased heat shock
      protein 90 (Hsp90) expression. Immunoprecipitation analysis confirmed that OLA
      NO2 replaced eNOS/Cav-1 with eNOS/Hsp90 interaction, resulting in increasing eNOS
      activity. OLA-NO2 also induced eNOS phosphorylation at Ser633 and Ser1177 and
      eNOS dephosphorylation at Ser113 and Thr495. In addition, OLA-NO2 induced
      phosphorylation of Akt and extracellular signal-regulated protein kinase
      (ERK1/2), which might contribute to eNOS activation. Collectively, these results
      substantiate a new functional role for nitrated fatty acid, demonstrating that
      OLA-NO2 exerts vascular protective effects by increasing NO bioavailability
      through eNOS phosphorylation/dephosphorylation and interaction with associated
      proteins such as Hsp90 and Cav-1. 

PMID- 24664543
TI  - Fibro-osseous lesions of the craniofacial bones: beta-catenin immunohistochemical
      analysis and CTNNB1 and APC mutation analysis.
AB  - The canonical Wnt/beta-catenin pathway is involved in the formation of
      craniofacial skeleton and oral tissues. Aberrant nuclear localization of beta
      catenin protein has been described in several human diseases including a subset
      of odontogenic tumors thereby suggesting an important role in tumor development.
      Fibro-osseous lesions of the craniofacial skeleton comprise several neoplastic,
      and reactive mesenchymal proliferations in which beta-catenin status is unknown.
      To study this, we immunostained 171 fibro-osseous lesions for beta-catenin
      protein and, for lesions with nuclear positivity, sequenced exon 3 of the CTNNB1
      gene and exon 15 of the APC gene. Nuclear beta-catenin immunostaining was
      detected in 34 (20 %) tumors with no correlation between nuclear positivity and
      either age, gender, or tissue decalcification status (p = 0.2, 0.17, 0.12,
      respectively). Absent nuclear beta-catenin in fibrous dysplasia was the only
      diagnostically significant finding (p = 0.0034). A single point mutation at Asp56
      of CTNNB1 was identified in one case of ossifying fibroma. A second ossifying
      fibroma and one desmoplastic fibroma demonstrated point mutations (Glu1317 and
      Glu1536, respectively [corrected] ) in the APC gene. These findings show that
      apart from fibrous dysplasia where nuclear beta-catenin is rare, nuclear beta
      catenin staining has limited utility in discriminating among the craniofacial
      fibro-osseous lesions. The molecular mechanisms underlying nuclear beta-catenin
      accumulation in the positive tumors is unlikely to be mediated by CTNNB1 exon 3
      or APC exon 15 mutations in most cases.

PMID- 24664544
TI  - Skin Biomechanical Changes after Injection of Onabotulinum Toxin A: Prospective
      Assessment of Elasticity and Pliability.
AB  - OBJECTIVE: This study aimed to test the hypothesis that the administration of
      onabotulinum toxin A will result in an increase in skin pliability and
      elasticity. STUDY DESIGN: A prospective case series with planned data collection
      in which patients were treated with onabotulinum toxin and assessed at baseline,
      2 weeks post-injection, and 2 months post-injection. SETTING: A private cosmetic
      surgery clinic associated with a tertiary academic hospital. SUBJECTS AND
      METHODS: Forty women were prospectively enrolled to receive onabotulinum toxin A
      into their glabella, forehead, and lateral orbit. Outcomes were assessed at
      baseline, 2 weeks posttreatment, and 2 months posttreatment using the Cutometer
      MPA 580. Skin pliability (Uf) and the elastic recoil (Ua/Uf) were recorded as the
      2 primary outcome measures. RESULTS: There was a significant effect of
      onabotulinum toxin on skin elasticity (f = 47.8, P = .001) with a mean (+/- SE)
      increase in elastic recoil of 20% (4.4%) for the glabellar region (P < .001) and
      18% (4.0%) for the lateral orbit (P < .0001). There was a significant effect of
      the treatment on skin pliability (f = 46.9, P < .001) with a mean (+/- SE)
      increase of 26% (5.4%) for the lateral orbit (P = .001) and 52% (8.3%) for the
      glabellar region (P < .001). CONCLUSION: Injection of onabotulinum toxin into the
      lateral orbital, forehead, and glabellar regions results in skin that has
      increased pliability as well as increased elastic recoil. Although this study
      demonstrates the positive effect of onabotulinum toxin on biomechanical
      parameters, it is unclear what specific histological changes are occurring within
      the skin.

PMID- 24664542
TI  - Two Chinese pedigrees for adenomatous polyposis coli: new mutations at codon 1309
      and predisposition to phenotypic variations.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease
      caused by a mutation in the adenomatous polyposis coli (APC) gene. Some studies
      have attempted to correlate mutations at codon 1309 with classic FAP (>=100
      colorectal polyps). We report two Chinese FAP pedigrees with new frameshift
      mutations at codon 1309, in which affected individuals manifest phenotypic
      variations. Comprehensive physical examinations were performed for all living
      individuals and the medical data of deceased patients were collected. Screening
      of the APC and human mutY homolog (MUTYH) genes for germline mutations was
      conducted by direct polymerase chain reaction (PCR) sequencing. In two pedigrees,
      a heterozygous deletion in exon 16 of the APC gene was present in all FAP
      patients but absent in the unaffected individuals. There were no changes to the
      MUTYH gene. The first pedigree, with a new frameshift mutation at c.3926_3930 del
      AAAAG (p. Glu1309Aspfs X4), exhibited obvious differences in the polyp number
      such that the proband manifested only three colorectal polyps, whereas another
      patients showed the symptoms of classic FAP. The second pedigree, also traced a
      new mutation at c.3922_3925 del AAAG (p. Glu1309Argfs X11). Although all of the
      patients presented with classic polyposis, one of them exhibited a delayed onset
      of colorectal cancer in his 50s. Two novel mutations at codon 1309 in two Chinese
      families suffering from FAP could enrich the germline mutation spectrum of the
      APC gene. Families of individuals might manifest different phenotypes, even with
      an identical codon 1309 mutation, unlike in previous studies. 

PMID- 24664545
TI  - Utility of Stepping, Walking, and Head Impulses for Screening Patients for
      Vestibular Impairments.
AB  - OBJECTIVE: To determine if some common screening tests predict scores on
      detailed, objective diagnostic tests of the vestibular system. STUDY DESIGN:
      Sixty patients with vestibular disorders were compared with 60 asymptomatic
      controls. SETTING: Vestibular diagnostic laboratory, tertiary care center.
      SUBJECTS AND METHODS: Subjects were screened with head impulse tests, Fukuda
      stepping tests while walking and marching in place, and tandem walking tests with
      eyes open and closed. All subjects underwent bithermal caloric tests and Dix
      Hallpike maneuvers; patients underwent low-frequency sinusoidal tests of the
      vestibulo-ocular reflex in darkness and cervical vestibular evoked myogenic
      potentials. RESULTS: On tandem walking tests, patients differed significantly
      from controls, but receiver operating characteristic scores were < 0.80. On
      Fukuda tests, patients turned significantly more than controls for walking but
      not marching, but receiver operating characteristic values were considerably less
      than 0.80. On head impulse tests, patients with bithermal caloric weakness (>=20%
      and <60%) did not differ from controls, but patients with severe bithermal
      caloric weakness (>=60%) differed significantly from controls. Receiver operating
      characteristic values were >0.80 only for subjects with severe bithermal caloric
      weakness and were highest, at 0.88, for subjects with severe weakness and age >=
      60 years. CONCLUSIONS: The Fukuda test is a poor screening test because it does
      not correlate well with objective test findings. Tandem walking is best used for
      screening older patients for vestibular disorders. Positive findings on a head
      impulse test are probably consistent with severe peripheral vestibular impairment
      and may be most useful in older patients. In younger patients with vertigo,
      negative results on head impulse tests may not be informative.

PMID- 24664546
TI  - Surgical Anatomy of the Infralabyrinthine Approach.
AB  - OBJECTIVE: The objective of this study is to demonstrate the surgical anatomy of
      the infralabyrinthine approach (ILA) and ways to prevent complications based on
      the complex anatomy. STUDY DESIGN: Cadaveric study. SETTING: Ankara University
      Faculty of Medicine, Department of Anatomy. SUBJECTS AND METHODS: Temporal bones
      were selected from 30 sides of 20 fixed human cadaver heads. Computed tomography
      (CT) scans of the heads were performed and, afterward, the cadavers were
      dissected using a surgical microscope and electric drill. RESULTS: An appropriate
      tract could be achieved in 73.3% of the dissections by applying slight pressure
      to the jugular bulb (JB). The narrowest portion of the ILA was defined as the
      inner window, which was located superior-inferiorly between the inferior border
      of the cochlea and the inferior wall of the petrous apex and anterior-posteriorly
      between the posterior wall of the carotid canal and the cochlear opening of the
      cochlear aqueduct. The ILA could not be performed when the distances between the
      facial nerve-JB and JB-cochlea were less than 2.9 mm and 2.6 mm, respectively, on
      CT scan. CONCLUSION: Close attention should be paid to the access and inner
      window during preoperative temporal bone imaging to assess for ILA. The detailed
      anatomy of the route, measurements of the topography of the cochlea from the
      mastoid view, and angles of the route are defined to prevent complications.

PMID- 24664547
TI  - Cycloaddition of carbon dioxide and epoxides using pentaerythritol and halides as
      dual catalyst system.
AB  - The combination of pentaerythritol with nucleophilic halide salts such as nBu4NI
      is used as a dual catalyst system for the cycloaddition of carbon dioxide (CO2)
      with a broad range of organic epoxides yielding the respective cyclic carbonates.
      Due to synergistic effects of the organocatalysts, excellent yields and
      selectivities could be achieved under mild reaction conditions. Moreover, the
      nontoxic, cost-efficient, and readily available system is easily recyclable
      without significant loss of reactivity, representing an exceptional sustainable
      approach for the fixation of CO2.

PMID- 24664548
TI  - Fibrin accumulation secondary to loss of plasmin-mediated fibrinolysis drives
      inflammatory osteoporosis in mice.
AB  - OBJECTIVE: Osteoporosis is a skeletal disorder characterized by low bone mass and
      increased bone fragility associated with aging, menopause, smoking, obesity, or
      diabetes. Persistent inflammation has been identified as an instigating factor in
      progressive bone loss. In addition to the role of fibrin in coagulation,
      inordinate fibrin deposition within a tissue matrix results in increased local
      inflammation. Given that fibrin accumulation is a hallmark of osteoporosis
      related comorbidities, we undertook this study to test the hypothesis that
      persistent fibrin deposition causes inflammatory osteoporosis. METHODS: Multiple
      imaging modalities, bone integrity metrics, and histologic analyses were employed
      to evaluate skeletal derangements in relation to fibrin deposition, circulating
      fibrinogen levels, and systemic markers of inflammation in mice that were
      plasminogen deficient and in plasminogen-deficient mice that were concomitantly
      either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the
      alphaM beta2 binding motif. RESULTS: Mice generated with a genetic deficit in the
      key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis.
      Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the
      derangements in the bone remodeling unit were mechanistically tied to
      fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte
      integrin receptor alphaM beta2 on monocytes and secondary stimulation of
      osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the
      expression of a mutant form of fibrinogen retaining clotting function but lacking
      the alphaM beta2 binding motif prevented the degenerative skeletal phenotypes,
      resulting in normal local and systemic cytokine levels. CONCLUSION: Taken
      together, these data reveal for the first time that fibrin promotes inflammation
      driven systemic osteoporosis, which suggests a novel association between
      hemostasis, inflammation, and bone biology.

PMID- 24664549
TI  - Physical properties of sugar cookies containing chia-oat composites.
AB  - BACKGROUND: Omega-3 fatty acids of chia seeds (Salvia hispanica L.) and soluble
      beta-glucan of oat products are known for lowering blood cholesterol and
      preventing coronary heart disease. Nutrim, oat bran concentrate (OBC), and whole
      oat flour (WOF) were composited with finely ground chia, and used in cookies at
      20% replacement of wheat flour for improved nutritional and physical quality. The
      objective was to evaluate physical properties of chia-oat composites, dough, and
      cookies. RESULTS: These composites had improved water-holding capacities compared
      to the starting materials. The geometrical properties and texture properties of
      the cookies were not greatly influenced by a 20% flour replacement using chia-OBC
      or chia-WOF composites. There was a decrease in the cookie diameter, and
      increases in the height of cookies and dough hardness using 20% Chia- Nutrim
      composite. CONCLUSION: These fine-particle chia-oat composites were prepared by a
      feasible procedure for improved nutritional value and physical properties of
      foods. The cookies containing chia-oat composites can be considered a health
      promoting functional food.

PMID- 24664550
TI  - Highly sensitive KRAS mutation detection from formalin-fixed paraffin-embedded
      biopsies and circulating tumour cells using wild-type blocking polymerase chain
      reaction and Sanger sequencing.
AB  - BACKGROUND AND OBJECTIVES: Among patients with colorectal cancer (CRC), KRAS
      mutations were reported to occur in 30-51 % of all cases. CRC patients with KRAS
      mutations were reported to be non-responsive to anti-epidermal growth factor
      receptor (EGFR) monoclonal antibody (MoAb) treatment in many clinical trials.
      Hence, accurate detection of KRAS mutations would be critical in guiding the use
      of anti-EGFR MoAb therapies in CRC. METHODS: In this study, we carried out a
      detailed investigation of the efficacy of a wild-type (WT) blocking real-time
      polymerase chain reaction (PCR), employing WT KRAS locked nucleic acid blockers,
      and Sanger sequencing, for KRAS mutation detection in rare cells. Analyses were
      first conducted on cell lines to optimize the assay protocol which was
      subsequently applied to peripheral blood and tissue samples from patients with
      CRC. RESULTS: The optimized assay provided a superior sensitivity enabling
      detection of as little as two cells with mutated KRAS in the background of 10(4)
      WT cells (0.02 %). The feasibility of this assay was further investigated to
      assess the KRAS status of 45 colorectal tissue samples, which had been tested
      previously, using a conventional PCR sequencing approach. The analysis showed a
      mutational discordance between these two methods in 4 of 18 WT cases. CONCLUSION:
      Our results present a simple, effective, and robust method for KRAS mutation
      detection in both paraffin embedded tissues and circulating tumour cells, at
      single-cell level. The method greatly enhances the detection sensitivity and
      alleviates the need of exhaustively removing co-enriched contaminating
      lymphocytes.

PMID- 24664551
TI  - Is there a relationship between the number of lymph nodes and disease parameters
      in patients who underwent retropubic prostatectomy.
AB  - PURPOSE: We aimed to establish the relationship between lymph nodes (LNs) counts
      that were removed with standard pelvic lymph node dissection (sPLND) and
      different disease parameters in patients who underwent radical prostatectomy
      (RP). MATERIALS AND METHODS: A total of 70 patients who underwent sPLND during RP
      were scanned retrospectively. The scanned parameters were levels of serum PSA,
      the total weight of the removed prostate, the amount as a percentage of the tumor
      in the prostate tissue, the stage of the tumor, the total Gleason score (GS) and
      the number of standard pelvic lymph nodes that were removed from both right and
      left sides. RESULTS: The average age of the patients was 59 years. A positive
      correlation was found between the total GS and the number of lymph nodes; while
      this correlation was significant (p = 0.0038), there was no significant
      difference between lymph nodes counts and other scanned parameters. The average
      pelvic lymph node numbers of patients with GS of 6-7 and 8 were 10.4-11.5 and
      13.2, respectively. Lymph nodes metastases were found in 3 (4.2 %) patients whose
      average pelvic lymph node number was 17.3. CONCLUSION: The chance of cure or
      decreased recurrence is much more possible in patients who had received extended
      PLND or at least standard one, because of the removal of much more lymph node
      tissues that have a high probability of disseminating cancer cells. This position
      can especially be considered in patients with high GS.

PMID- 24664552
TI  - An economic analysis of prenatal cytogenetic technologies for sonographically
      detected fetal anomalies.
AB  - When congenital anomalies are diagnosed on prenatal ultrasound, the current
      standard of care is to perform G-banded karyotyping on cultured amniotic cells.
      Chromosomal microarray (CMA) can detect smaller genomic deletions and
      duplications than traditional karyotype analysis. CMA is the first-tier test in
      the postnatal evaluation of children with multiple congenital anomalies. Recent
      studies have demonstrated the utility of CMA in the prenatal setting and have
      advocated for widespread implementation of this technology as the preferred test
      in prenatal diagnosis. However, CMA remains significantly more expensive than
      karyotype. In this study, we performed an economic analysis of cytogenetic
      technologies in the prenatal diagnosis of sonographically detected fetal
      anomalies comparing four strategies: (i) karyotype alone, (ii) CMA alone, (iii)
      karyotype and CMA, and (iv) karyotype followed by CMA if the karyotype was
      normal. In a theoretical cohort of 1,000 patients, CMA alone and karyotype
      followed by CMA if the karyotype was normal identified a similar number of
      chromosomal abnormalities. In this model, CMA alone was the most cost-effective
      strategy, although karyotype alone and CMA following a normal karyotype are both
      acceptable alternatives. This study supports the clinical utility of CMA in the
      prenatal diagnosis of sonographically detected fetal anomalies.

PMID- 24664553
TI  - Leptin and adiponectin receptor expression in oesophageal cancer.
AB  - BACKGROUND: Oesophageal adenocarcinoma is an exemplar model of an obesity
      associated adenocarcinoma. Altered secretion of adipokines by visceral fat is
      believed to play a key role in tumorigenesis. This study examined leptin receptor
      (ObR) and adiponectin receptor (AdipoR1 and AdipoR2) expression in oesophageal
      cancer, and its relationship with patient obesity status, clinicopathological
      data and patient survival. METHODS: Tissue microarrays were constructed from
      paraffin-embedded oesophagectomy specimens. ObR, AdipoR1 and AdipoR2 expression
      was quantified by immunohistochemistry. Anthropometric data were measured at the
      time of diagnosis, and obesity status was assessed using visceral fat area
      determined by computed tomography and body mass index. Receptor expression was
      correlated with various clinicopathological and anthropometric variables. Patient
      survival was estimated using the Kaplan-Meier method, and results compared
      between those with low versus high receptor expression. A Cox multivariable
      regression model was used to assess the relationship between survival and a
      number of co-variables. RESULTS: All 125 tumours analysed expressed AdipoR1 and
      AdipoR2, whereas 96.8 per cent expressed ObR. There was no significant difference
      in tumour pathological features or patient obesity status between tumours with
      low versus high ObR expression. A high level of AdipoR1 expression was
      significantly associated with increased patient age, obesity and less advanced
      tumour (T) category. Expression of AdipoR2 was inversely associated with T
      category (P = 0.043). Low AdipoR1 expression was an independent predictor of
      improved overall survival (hazard ratio 0.56, 95 per cent confidence interval
      0.35 to 0.90; P = 0.017). CONCLUSION: The association between adiponectin
      receptor expression, obesity status and tumour category and survival suggests a
      potential mechanism linking obesity and oesophageal cancer.

PMID- 24664554
TI  - Physiology and Endocrinology Symposium: The next generation of metabolic
      endocrinology.

PMID- 24664555
TI  - A post-transcriptional mechanism regulates calpastatin expression in bovine
      skeletal muscle.
AB  - The objective of this study was to investigate whether single nucleotide
      polymorphisms (SNP) in the calpain 1 (CAPN1), calpain 3 (CAPN3) and calpastatin
      (CAST) genes, which have been shown to be associated with shear force and
      tenderness differences in the skeletal muscle of cattle, contribute to phenotypic
      variation in muscle tenderness by modulating the transcriptional activity of
      their respective gene. The mRNA expression of the calpain and CAST genes was
      assessed in the longissimus lumborum muscle (LLM) of cattle from two herds
      located in distinct production zones on the east (New South Wales, NSW) and west
      (Western Australia, WA) of Australia. The cattle in the herds were mainly Brahman
      cattle (Bos indicus) with smaller populations of Angus cattle (Bos taurus). There
      were 191 steers in the WA herd and 107 steers and 106 heifers in the NSW herd.
      These herds were established by choosing cattle from the diverse population which
      had different single nucleotide polymorphism (SNP) genotypes at the CAPN1, CAPN3
      and CAST loci. Using quantitative reverse transcriptase polymerase chain reaction
      (qRT-PCR), the transcriptional activities of the CAPN1 and the CAST genes, but
      not the CAPN3 gene, were found to differ between favorable, positively associated
      with tenderness, and unfavorable, negatively associated with tenderness, allelic
      variants of these genes. These findings suggest that the muscle shear force and
      consumer taste panel differences in tenderness explained by the CAPN1 and CAST
      gene markers are a consequence of alterations in their mRNA levels, which may
      ultimately influence the protein activity of these genes, thereby altering the
      rate and(or) the extent of postmortem proteolysis in skeletal muscle. Of
      particular importance were the significantly lower type II and type III CAST 5'
      splice variant mRNA levels that were detected in the LLM muscle of Brahman and
      Angus cattle with 2 favourable alleles of the CAST:c.2832A > G polymorphism.
      Moreover, a reduction in the abundance of an alternative polyadenylated variant
      of the CAST transcript, terminated at the proximal polyadenylation site, provides
      a unique insight into the potential involvement of a post-transcriptional
      regulatory mechanism which may influence protein expression levels in bovine
      skeletal muscle.

PMID- 24664556
TI  - Towards an improved estimation of the biological components of residual feed
      intake in growing cattle.
AB  - Residual feed intake (RFI) is the difference between observed and predicted feed
      intake. It is calculated as the residuals from a multiple regression model of DMI
      on the various energy expenditures (e.g., maintenance, growth, activity).
      Residual feed intake is often cited to be indicative of feed efficiency
      differences among animals. However, explaining a large proportion of the
      (phenotypic and genetic) interanimal variation in RFI remains difficult. Here we
      first describe a biological framework for RFI dwelling on similarities between
      RFI and energy balance. Alternative phenotypic and genetic statistical models are
      subsequently applied to a dataset of 1,963 growing bulls of 2 British and 3
      Continental breeds. The novel aspect of this study was the use of a mixed model
      framework to quantify the heritable interanimal variation in the partial
      regression coefficients on the energy expenditure traits within the RFI equation.
      Heritable genetic variation in individual animal regression coefficients for
      metabolic live weight existed. No significant genetic variation in animal-level
      regression coefficients for growth or body fat level, however, existed in the
      study population. The presence of genetic variation in the partial regression
      coefficient of maintenance suggests the existence of interanimal variation in
      maintenance efficiency. However, it could also simply reflect interanimal genetic
      variation in correlated energy expenditure traits not included in the statistical
      model. Estimated breeding values for the random regression coefficient could be
      useful phenotypes in themselves for studies wishing to elucidate the underlying
      mechanisms governing differences among animals in RFI. 

PMID- 24664557
TI  - Lifetime reproductive performance and survival analysis of mice divergently
      selected for heat loss.
AB  - Divergent selection for heat loss was implemented in mice creating maintenance
      high (MH) and low maintenance (ML) lines and an unselected control (MC) in 3
      independent replicates. Mice from the ML line have improved feed efficiency, due
      to decreased maintenance energy requirement, but there is potential for a
      correlated decline in reproductive performance and survivability. Number fully
      formed (NFF), number born alive (NBA), number weaned (NW), litter weaning weight
      (LWW), pup weaning weight (PWW), fraction alive at birth (FAB), fraction alive at
      weaning, and birth interval were recorded at every parity on 21 mating pairs from
      each line * replicate combination cohabitated at 7 wk of age and maintained for
      up to 1 yr. Traits were summed over parities to evaluate lifetime production.
      Pairs were culled due to death or illness, no first parity by 42 d cohabitation,
      2 consecutive litters with none born alive, 3 consecutive litters with none
      weaned, 42 d between parities, or average size of most recent 2 litters less than
      half the average of first 3 litters. Survival probabilities were produced and
      evaluated for each line and used to calculate mean number of parities using a
      Markov-chain algorithm assuming a maximum of 4, 6, 8, 10, or 12 parities or 1 yr.
      Line was insignificant for all litter traits while NFF, NW, and FAB decreased
      with parity (P < 0.05) and PWW tended to increase (P < 0.07). The MC mice had
      higher lifetime NW, LWW, and PWW (P < 0.04). Birth interval showed that MH mice
      had increasingly larger intervals while remaining the same in ML mice (P < 0.01).
      In the survival analysis, MC mice had the greatest survival rates overall, but ML
      mice had the greatest rates in the period up to 5 parities while MH mice had the
      greatest rates in later parities. This resulted in greater mean number of
      parities for ML mice up to maximum of 8 parities and higher means for MH mice
      when the maximum number of allowed parities was 10 or higher. Reproductive
      performance was not substantially affected by changing maintenance energy
      requirements. The ML animals appear to survive well in early parities and produce
      more parities when a low number of maximum parities is enforced, but this benefit
      declines in later parities and MH animals survive better and increase mean number
      of parities when turnover rates are low. Therefore, selection for low maintenance
      animals may be beneficial for systems desiring a short generation interval but
      less so for systems desiring longevity. 

PMID- 24664558
TI  - Impact of oral meloxicam on circulating physiological biomarkers of stress and
      inflammation in beef steers after long-distance transportation.
AB  - Transportation stress can result in significant economic losses to producers due
      to decreased animal productivity and increased medication costs associated with
      sickness such as bovine respiratory disease (BRD). Meloxicam (MEL) provides pain
      relief and anti-inflammatory effects in cattle for several days after a single
      oral treatment. Our hypothesis was that MEL administration before shipping would
      reduce the impact of long-distance transportation on circulating physiological
      biomarkers of stress and inflammation in beef steers. Ninety-seven beef steers
      were blood sampled for baseline biomarker determination and then randomly
      assigned to receive either 1 mg/kg MEL (n = 49) or a placebo (CONT; n = 48) per
      os before a 1,316-km transportation event lasting approximately 16 h. Calves were
      then blood sampled on arrival and 5 d later. Changes in the hemogram, circulating
      plasma proteins, total carbon dioxide (TCO2), fibrinogen, substance P (SP),
      cortisol, haptoglobin (Hp)-matrix metalloproteinase-9 (MMP-9) complexes, and
      tumor necrosis factor alpha (TNFalpha) between treatments over time were compared
      using a mixed effects model with statistical significance designated as P < 0.05.
      Analysis of covariance was conducted to assess the relationship between
      circulating MEL concentrations and biomarker changes over time. An increase in
      neutrophil, platelet, monocyte, white blood cell, and red blood cell counts
      occurred after transportation (P < 0.0001) and a decrease in lymphocyte count
      were observed (P < 0.0001). Meloxicam treatment reduced the stress-induced
      neutrophilia (P = 0.0072) and circulating monocyte count (P = 0.013) on arrival.
      Mean corpuscle hemoglobin (P = 0.05), mean corpuscle volume (P = 0.05), and
      lymphocyte count (P = 0.05) were also greater in the CONT calves compared with
      MEL calves after transportation. Furthermore, Hp-MMP-9 complexes, TCO2, TNFalpha,
      plasma proteins, and SP increased and cortisol decreased after shipping (P <
      0.01). Meloxicam treatment tended to reduce serum cortisol concentrations (P =
      0.08) and there was evidence of a time * treatment interaction (P = 0.04). An
      inverse relationship between plasma MEL concentrations and circulation cortisol
      concentrations (P = 0.002) and neutrophil (P = 0.04) and basophil counts (P =
      0.03) was also observed. The results suggest that MEL administration may reduce
      the impact of long-distance transportation on circulating physiological
      biomarkers of stress and inflammation in beef calves.

PMID- 24664559
TI  - Effects of fibroblast growth factor 9 on steroidogenesis and control of FGFR2IIIc
      mRNA in porcine granulosa cells.
AB  - The objectives of this study were to investigate the effects of fibroblast growth
      factor 9 (FGF9) on hormone-stimulated porcine granulosa cell proliferation and
      steroid production and to further elucidate the hormonal and developmental
      control of FGFR2IIIc gene expression in granulosa cells. Porcine ovaries were
      collected from a local slaughterhouse and granulosa cells were collected from
      small to medium (1 to 5 mm) follicles for 5 in vitro studies that were conducted.
      Cells were cultured for 48 h in 5% fetal calf serum plus 5% porcine serum and
      then treated with various combinations of FSH, IGF-I, FGF9, Sonic hedgehog (SHH),
      cortisol, PGE2, and/or wingless-type mouse mammary tumor virus integration site
      family member 5A (WNT5A) in serum-free medium for an additional 24 or 48 h.
      Medium was collected for analysis of steroid concentration via RIA, or RNA was
      collected for gene expression analysis of FGFR2IIIc via quantitative reverse
      transcription PCR. Fibroblast growth factor 9 stimulated (P < 0.05) IGF-I-induced
      estradiol production in the presence of FSH and testosterone. However, FGF9 had
      inconsistent effects on progesterone production, stimulating progesterone
      production in the presence of FSH and testosterone but inhibiting progesterone
      production in the presence of IGF-I, FSH, and testosterone. Cell numbers were
      increased (P < 0.05) by FGF9 in the presence of IGF-I and FSH but not in the
      presence of FSH and absence of IGF-I. For FGFR2IIIc mRNA studies, granulosa cells
      were treated with FSH, IGF-I, FGF9, SHH, cortisol, PGE2, or WNT5A. Follicle
      stimulating hormone alone had no effect (P > 0.10) whereas IGF-I increased (P <
      0.05) FGFR2IIIc mRNA abundance. Cortisol, PGE2, SHH, and WNT5A had no effect (P >
      0.10) on FGFR2IIIc gene expression whereas FGF9 in the presence of FSH and IGF-I
      inhibited (P < 0.05) FGFR2IIIc gene expression. In an in vivo study, granulosa
      cells from large (7 to 14 mm) follicles had greater (P < 0.05) abundance of
      FGFR2IIIc mRNA than small (1 to 3 mm) or medium (4 to 6 mm) follicles. In
      conclusion, IGF-I-induced FGFR2IIIc mRNA may be a mechanism for increased
      responses to FGF9 in FSH plus IGF-I-treated granulosa cells. Fibroblast growth
      factor 9 and IGF-I may work together as amplifiers of follicular growth and
      granulosa cell differentiation by stimulating estradiol production and
      concomitantly stimulating granulosa cell growth in pigs.

PMID- 24664560
TI  - Effects of maternal nutrient restriction followed by realimentation during early
      and midgestation on beef cows. I. Maternal performance and organ weights at
      different stages of gestation.
AB  - The objectives were to evaluate the effects of nutrient restriction during early
      to midgestation followed by realimentation on maternal performance and organ mass
      in pregnant beef cows. On d 30 of pregnancy, multiparous, nonlactating cows
      (initial BW = 620.5 +/- 11.3 kg and BCS = 5.1 +/- 0.1) were assigned to 1 of 3
      dietary treatments: control (CON; 100% NRC; n = 18) and restricted (RES; 60% NRC;
      n = 30). On d 85, cows were slaughtered (CON, n = 6; R, n = 6), remained on
      control (CC; n = 12) and restricted (RR; n = 12), or were realimented to control
      (RC; n = 11). On d 140, cows were slaughtered (CC, n = 6; RR, n = 6; RC, n = 5),
      remained on control (CCC, n = 6; RCC, n = 5), or were realimented to control
      (RRC, n = 6). On d 254, all remaining cows were slaughtered. Cows were weighed
      before slaughter and all maternal organs were dissected and weighed. The diet
      consisted of grass hay to meet 100 or 60% NEm recommendations for fetal growth
      and to meet or exceed recommendations for other nutrients. At d 85 slaughters, BW
      and empty BW (EBW) were not affected (P >= 0.84) by maternal nutrition. However
      back fat was decreased (P = 0.05) in RES vs. CON cows. Large intestine and
      abomasum mass were increased (P <= 0.05) in RES cows vs. CON. At d 140, BW was
      decreased (P = 0.05) and EBW tended to be decreased (P = 0.10) in RRC cows vs.
      CCC and RCC being intermediate. Liver mass was decreased (P = 0.02) in RR vs. CC
      with RC being intermediate. Ruminal mass was decreased (P = 0.003) in RR vs. CC
      and RC cows. At d 254, BW and EBW were similar (P >= 0.78) across treatments. We
      observed partial changes in maternal weight and organ masses due to different
      lengths of maternal nutrient restriction followed by realimentation. It appears
      that the dam undergoes some adaptations during an early to midgestation nutrient
      restriction and becomes more efficient in the utilization of nutrients after
      being realimented and as gestation advances.

PMID- 24664561
TI  - Effect of collection-maturation interval time and pregnancy status of donor mares
      on oocyte developmental competence in horse cloning.
AB  - The current limitations for obtaining ovaries from slaughterhouses and the low
      efficiency of in vivo follicular aspiration necessitate a complete understanding
      of the variables that affect oocyte developmental competence in the equine. For
      this reason, we assessed the effect on equine oocyte meiotic competence and the
      subsequent in vitro cloned embryo development of 1) the time interval between
      ovary collection and the onset of oocyte in vitro maturation (collection
      maturation interval time) and 2) the pregnancy status of the donor mares. To
      define the collection-maturation interval time, collected oocytes were classified
      according to the slaughtering time and the pregnancy status of the mare.
      Maturation rate was recorded and some matured oocytes of each group were used to
      reconstruct zona free cloned embryos. Nuclear maturation rates were lower when
      the collection-maturation interval time exceeded 10 h as compared to 4 h (32/83
      vs. 76/136, respectively; P = 0.0128) and when the donor mare was pregnant as
      compared to nonpregnant (53/146 vs. 177/329, respectively; P = 0.0004). Low rates
      of cleaved embryos were observed when the collection-maturation interval time
      exceeded 10 h as compared to 6 to 10 h (11/27 vs. 33/44, respectively; P =
      0.0056), but the pregnancy status of donor mares did not affect cloned equine
      blastocyst development (3/49 vs. 1/27 for blastocyst rates of nonpregnant and
      pregnant groups, respectively; P = 1.00). These results indicate that, to apply
      assisted reproductive technologies in horses, oocytes should be harvested within
      approximately 10 h after ovary collection. Also, even though ovaries from
      pregnant mares are a potential source of oocytes, they should be processed at the
      end of the collection routine due to the lower collection and maturation rate in
      this group.

PMID- 24664562
TI  - The effect of dietary hydroxyproline and dietary oxalate on urinary oxalate
      excretion in cats.
AB  - In humans and rodents, dietary hydroxyproline (hyp) and oxalate intake affect
      urinary oxalate (Uox) excretion. Whether Uox excretion occurs in cats was tested
      by feeding diets containing low oxalate (13 mg/100 g DM) with high (Hhyp-Lox),
      moderate (Mhyp-Lox), and low hyp (Lhyp-Lox) concentrations (3.8, 2.0, and 0.2
      g/100 g DM, respectively) and low hyp with high oxalate (93 mg/100 g DM; Lhyp
      Hox) to 8 adult female cats in a 48-d study using a Latin square design. Cats
      were randomly allocated to one of the four 12-d treatment periods and fed
      according to individual energy needs. Feces and urine were collected
      quantitatively using modified litter boxes during the final 5 d of each period.
      Feces were analyzed for oxalate and Ca, and urine was analyzed for specific
      density, pH, oxalate, Ca, P, Mg, Na, K, ammonia, citrate, urate, sulfate, and
      creatinine. Increasing hyp intake (0.2, 2.0, and 3.8 g/100 g DM) resulted in
      increased Uox excretion (Lhyp-Lox vs. Mhyp-Lox vs. Hhyp-Lox; P < 0.05), and the
      linear dose-response equation was Uox (mg/d) = 5.62 + 2.10 * g hyp intake/d (r(2)
      = 0.56; P < 0.001). Increasing oxalate intake from 13 to 93 mg/100 g DM did not
      affect Uox excretion but resulted in an increase in fecal oxalate output (P <
      0.001) and positive oxalate balance (32.20 +/- 2.06 mg/d). The results indicate
      that the intestinal absorption of the supplemental oxalate, and thereby its
      contribution to Uox, was low (5.90% +/- 5.24%). Relevant increases in endogenous
      Uox excretion were achieved by increasing dietary hyp intake. The hyp-containing
      protein sources should be minimized in Ca oxalate urolith preventative diets
      until their effect on Uox excretion is tested. The oxalate content (up to 93
      mg/100 g DM) in a diet with moderate Ca content does not contribute to Uox
      content. 

PMID- 24664564
TI  - Effects of supplementing endophyte-infected tall fescue with sainfoin and
      polyethylene glycol on the physiology and ingestive behavior of sheep.
AB  - Tannins in sainfoin (Onobrychis viciifolia) may bind to alkaloids in endophyte
      infected tall fescue [E+; Lolium arundinaceum (Schreb.) Darbysh.] and attenuate
      toxicosis. If so, supplementing E+ with sainfoin will increase use of E+ by
      sheep, and polyethylene glycol (PEG)-a polymer that selectively binds to tannins
      will reduce such response. To test these predictions, thirty-six 2-mo-old lambs
      were randomly assigned to 3 treatments (12 lambs/treatment). During exposure, all
      lambs were individually penned and fed E+ supplemented with beet pulp (CTRL),
      fresh-cut sainfoin and beet pulp (SAIN), or fresh-cut sainfoin plus PEG mixed in
      beet pulp (SAIN+PEG). Feed intake was measured daily. Rectal temperatures and
      jugular blood samples were taken at the beginning and end of exposure. After
      exposure, all lambs were offered choices between endophyte-free tall fescue (E-)
      and orchardgrass, and preference for E- was assessed. Then, all lambs were
      allowed to graze a choice of E+ and sainfoin or a monoculture of E+. The foraging
      behavior of lambs was recorded. When sainfoin was in mid-vegetative stage, lambs
      in SAIN ingested more E+ than lambs in CTRL (P = 0.05), but no differences were
      detected between lambs in SAIN+PEG and CTRL (P = 0.12). Sainfoin supplementation
      improved some physiological parameters indicative of fescue toxicosis. Lambs in
      SAIN had lower rectal temperatures (P = 0.02), greater numbers of leukocytes (P <
      0.001) and lymphocytes (P = 0.03), and greater plasmatic concentrations of
      globulin (P = 0.009) and prolactin (P = 0.019) than lambs in CTRL. Some of these
      differences were offset by the SAIN+PEG treatment. When lambs were offered
      choices between E- and orchardgrass, only lambs in SAIN had greater intake of E-
      than lambs in CTRL (P < 0.001). When lambs were allowed to graze a choice of E+
      and sainfoin, all treatments used E+ to the same extent (P > 0.05). On the other
      hand, when they grazed on a monoculture of E+, lambs in SAIN+PEG showed greater
      acceptance of E+ than lambs in SAIN or in CTRL (P < 0.05). In summary, sainfoin
      supplementation alleviated several of the classic signs of fescue toxicosis and
      increased intake of endophyte-infected tall fescue. Tannins in sainfoin partially
      accounted for this benefit since feeding a polymer that selectively binds to
      tannins (PEG) attenuated some these responses. However, sainfoin supplementation
      during initial exposure to E+ did not lead to an increased preference for E+
      during grazing.

PMID- 24664563
TI  - Effect of feeding dried distillers grains with solubles on ruminal
      biohydrogenation, intestinal fatty acid profile, and gut microbial diversity
      evaluated through DNA pyro-sequencing.
AB  - The objectives of this study were to evaluate the effect of dried distillers
      grains with solubles (DDGS) on ruminal biohydrogenation and duodenal flow of
      fatty acids, and to evaluate effects on the ruminal and duodenal microbial
      community using Roche 454 pyro-sequencing. Three crossbred steers (average BW 780
      +/- 137 kg) fitted with ruminal and duodenal cannulae were used in a 3-diet, 6
      period crossover design. Animals were housed in individual free stalls and fed
      twice daily at 0700 and 1900 h. Diets (DM basis) were 1) CONTROL, 19.5% corn
      bran, 20% sorghum silage, 60% brome hay, 0.5% trace minerals, and 0.25% urea, but
      no DDGS; 2) LOW DDGS, inclusion of 9.75% DDGS replacing equal percentage of corn
      bran; 3) HIGH DDGS, inclusion of 19.5% DDGS completely replacing corn bran. Feed
      ingredients and duodenal digesta samples were analyzed for fatty acid
      composition. The DNA was extracted from isolated mixed ruminal bacterial samples
      and from intestinal digesta samples. The V1-V3 region of the 16S rRNA gene was
      sequenced, and bacterial phylogenetic analysis was conducted. Data were analyzed
      using the MIXED procedure of SAS. Biohydrogenation of C18:1 increased (P < 0.01)
      with DDGS inclusion; means were 68.3, 75.6, and 79.3 +/- 4.3% for CONTROL, LOW
      DDGS, and HIGH DDGS, respectively. In the same order, means of biohydrogenation
      of C18:2 (P < 0.05) were 84.1, 91.5, and 93.3 +/- 3.4%. Duodenal flow of total
      fatty acids increased (P < 0.01) with DDGS inclusion; means were 134, 168, and
      223 +/- 33 g/d for CONTROL, LOW DDGS, and HIGH DDGS, respectively. In the same
      order, means of C18:0 flow (P < 0.01) were 51, 86, and 121 +/- 18 g/d. DDGS did
      not affect the predominant bacterial phyla in the gut, which were Bacteroidetes
      (P = 0.62) and Firmicutes (P = 0.71). However, the phylum Fibrobacteres decreased
      (P < 0.01) when DDGS was fed with means of 5.5, 6.0 and 3.7 +/- 0.6% for CONTROL,
      LOW DDGS, and HIGH DDGS, respectively. Fibrobacteres were lower (P < 0.01) in
      isolated ruminal bacterial samples compared to duodenal digesta samples with
      means of 0.1 and 10.1 +/- 0.6%, respectively. Overall, the inclusion of DDGS in
      diets increased ruminal biohydrogenation of C18:1 and C18:2, which increased
      duodenal flow of C18:0. In addition, the bacterial community of the rumen
      clustered separately from that of the duodenum suggesting different bacterial
      diversity between isolated ruminal bacteria and duodenal digesta.

PMID- 24664565
TI  - Foraging behavior of two cattle breeds, a whole-year study: II. Spatial
      distribution by breed and season.
AB  - Spatial distributions of 22 mature large-framed Beefmaster * Simford (BS) cross
      cows and 16 mature small-framed Baladi (BA) cows were determined. Cows were
      allocated to the same paddock of a Mediterranean pasture and monitored during 6
      consecutive seasons: spring (April 2006), summer (June 2006), autumn (September
      2006), winter (February 2007), early spring (March 2007), and summer (June 2007).
      The locations of the cows were determined at 5-min intervals for 3 to 4 d during
      each season by using Global Positioning System (GPS) collars. The distances
      between consecutive locations and the average locations of each breed at each
      hour of the day in each season were calculated. The Lateral Foraging Index (LFI)
      was calculated as the ratio between the average distance per day travelled by the
      cows of each breed and the perimeter of the diurnal itinerary of that breed,
      which was calculated from its hourly average locations. The 2 breeds maintained
      similar diurnal patterns of foraging and resting, characterized by morning and
      afternoon foraging, and resting at midday and during the night. In summer this
      pattern was more distinctive, with longer resting periods and more intense
      foraging periods than in winter, when the noon rest was shorter and only partial.
      The diurnal routes differed (P < 0.001) between the breeds in all seasons, in
      their locations, their travelling time, or both. The BA cows were more active
      than the BS cows in all seasons: they travelled longer distances (P < 0.001) and
      foraged for more hours during the day (P < 0.001). For both breeds the LFI was
      numerically greater in winter and spring (February, and March) than in summer
      (June and September), and it was numerically greater for BA than for BS cows in
      most seasons. 

PMID- 24664566
TI  - The effects of porcine intestinal mucosa protein sources on nursery pig growth
      performance.
AB  - Three studies were conducted to compare the effects of 4 different porcine
      intestinal mucosa products (PEP2, PEP2+, Peptone 50, and PEP-NS; TechMix Inc.,
      Stewart, MN) with select menhaden fish meal (SMFM) on nursery pig performance.
      These intestine-derived mucosal ingredients are byproducts of heparin production,
      with a similar amount of mucosal protein, but differ based on the carriers with
      which they are co-dried. Enzymatically processed vegetable protein is the carrier
      for PEP2 whereas PEP2+ is co-dried with enzymatically processed vegetable
      proteins and biomass from crystalline AA production. Peptone 50 uses vegetable
      protein as its carrier while PEP-NS is co-dried with byproducts of corn wet
      milling and biomass from crystalline AA production. In Exp. 1, 300 weanling pigs
      (PIC 327 * 1050; initially 5.4 kg and 19 d of age) were allotted to 1 of 5
      dietary treatments with 12 replications and 5 pigs per pen. Diets consisted of a
      negative control (NC) containing no specialty protein sources, NC with 4, 8, or
      12% PEP2 in phases 1 (d 0 to 11) and 2 (d 11 to 25), and a positive control
      containing 4% spray-dried animal plasma (SDAP) in phase 1 and 4% SMFM in phase 2.
      From d 0 to 11, pigs fed SDAP had greater (P < 0.05) ADG and G:F than pigs fed
      PEP2. From d 11 to 25, increasing PEP2 increased (quadratic; P < 0.01) ADG and
      G:F, with the greatest response observed at 4%. In Exp. 2, 960 weanling pigs
      (Newsham GPK35 * PIC 380; initially 5.6 kg, and 20 d of age) were allotted to 1
      of 5 dietary treatments with 32 pigs per pen and 6 replications per treatment.
      Diets included a control with 4.5% SDAP in phase 1 (d 0 to 7) and no specialty
      protein sources in phase 2 (d 7 to 21) or the control diet with 6% of the
      following: SMFM, PEP2+, Peptone 50, or PEP-NS. From d 0 to 21, pigs fed diets
      containing SMFM, PEP2+, or PEP-NS had greater (P < 0.05) ADG than pigs fed the
      control or 6% Peptone 50. In Exp. 3, 180 nursery pigs (PIC 327 * 1050; initially
      6.4 kg and 28 d of age) were allotted to 1 of 5 dietary treatments with 5 pigs
      per pen and 6 replications per treatment. Treatment diets were fed from d 7 to 21
      postweaning. Treatments consisted of a NC, NC with 3, 6, 9, or 12% PEP-NS, or NC
      with 6% SMFM. Overall, pigs fed increasing PEP-NS had improved (quadratic; P <
      0.01) ADG and G:F, with the greatest improvement observed in pigs fed 6% PEP-NS,
      similar to those fed 6% SMFM. These results suggest PEP2, PEP2+, and PEP-NS can
      effectively replace SMFM in nursery pig diets. 

PMID- 24664567
TI  - Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs
      during gas euthanasia.
AB  - The objectives of this study were to assess efficacy and welfare implications of
      gas euthanasia when applied to weaned and neonate pigs. Parameters associated
      with welfare, which were measured before loss of consciousness, included open
      mouth breathing, ataxia, righting response, and escape attempts. Two age groups
      (weaned and neonate) were assessed in 9 gas treatments arranged in a 2 * 4
      factorial design, with 2 gas types (CO2 = 100% CO2 and 50:50 = 50:50 CO2:argon)
      and 4 flow rates (box volume exchange/min: slow = 20%; medium = 35%; fast = 50%;
      prefill = prefilled followed by 20%) and a control treatment in which ambient air
      was passed through the box. Pig pairs (10/treatment) were placed in a modified
      Euthanex AgPro system (Euthanex Corp., Palmer, PA). Behavioral and physiological
      responses were observed directly and from video recordings for latency, duration,
      prevalence (percent of pigs affected), and frequency (number of occurrences/pig).
      Data were analyzed as linear mixed models or with a Cox proportional hazard model
      as appropriate. Piglet pair was the experimental unit. For the weaned pig,
      welfare was superior with CO2 relative to 50:50 within 1 or more flow rates on
      the basis of reduced duration of open-mouth breathing, duration of ataxia,
      frequency of escape attempts, and duration and frequency of righting response (P
      < 0.05). No measured parameters indicated superior welfare with the use of 50:50,
      whereas latencies to loss of posture and last movement favored CO2 (P < 0.05).
      Faster flow rates were associated with reduced (P < 0.05) duration or frequency
      of open-mouth breathing, ataxia, and righting response, as well as superior (P <
      0.05) indicators of efficacy, including latencies to loss of posture, gasping,
      and last movement, relative to slower flow rates. Weaned pigs were more likely to
      defecate (P < 0.01), display nasal discharge (P < 0.05), and display longer (P <
      0.001) latencies to loss of posture and last movement than neonates. Duration of
      ataxia was the only parameter for which neonates were superior (P < 0.01) to
      weaned pigs during euthanasia. As such, a 50:50 CO2:argon gas mixture and slower
      flow rates should be avoided when euthanizing weaned or neonate pigs with gas
      methods. Neonate pigs succumb to the effects of gas euthanasia quicker than
      weaned pigs and display fewer signs of distress.

PMID- 24664568
TI  - Effects of methionine supplementation on the redox state of acute heat stress
      exposed quails.
AB  - The aims of the present study were to evaluate the possible effects of heat
      stress (HS) on H2O2 production and to evaluate whether methionine supplementation
      (MS) could mitigate the deleterious effects on cell metabolism and the redox
      state induced by oxidative stress. Meat quails (Coturnix coturnix coturnix) were
      fed a diet that either met the nutritional demands for methionine or did not meet
      this demand (methionine deficient [MD] diet) for 7 d. The animals were either
      kept at a thermal comfort temperature (25 degrees C) or exposed to HS (38 degrees
      C for 24 h, starting on the sixth day). Heat stress induced decreased food intake
      (P = 0.0140), decreased daily weight gain (P < 0.0001), and increased water
      intake (P = 0.0211). A higher rate of H2O2 production was observed in HS animals
      (0.0802 vs. 0.0692 nmol of reactive oxygen species [ROS] produced per minute per
      milligram of protein; P = 0.0042) and in animals fed with the MD diet (0.0808 vs.
      0.0686 nmol of ROS produced per minute per milligram of protein; P = 0.0020). We
      observed effects of the interaction between diet and the environment on the
      activities of glutathione peroxidase (GP-x) and catalase (P = 0.0392 and P <
      0.0001, respectively). Heat stress induced higher levels of GP-x activity in
      animals on the MS diet and higher catalase activity in animals on the MD diet.
      Glutathione (GSH) levels were higher in animals on the MS diet (P = 0.0273) and
      in animals that were kept in thermal comfort (P = 0.0018). The thiobarbituric
      acid reactive substances level was higher in HS animals fed with the MD diet (P =
      0.0386). Significant effects of the interaction between supplementation and
      environment were observed on uric acid concentration levels, which were higher in
      HS animals fed the MS diet (P = 0.008), and on creatine kinase activity levels,
      which were lower in HS animals fed the MD diet (1,620.33 units/L; P = 0.0442).
      Our results suggest that under HS conditions, in which H2O2 production is
      increased, MS was able to mitigate ROS-induced damage, possibly by increasing the
      activities of antioxidant elements such as GSH, GPx activity, and uric acid
      concentration, which were present in higher levels in animals that were subjected
      to HS and fed the MS diet.

PMID- 24664569
TI  - Impact of oral meloxicam administered alone or in combination with gabapentin on
      experimentally induced lameness in beef calves.
AB  - This study examined the pharmacokinetics and analgesic effect of oral meloxicam
      (MEL) administered alone or in combination with gabapentin (GABA) in an
      experimental bovine lameness model. Eighteen male British * Continental beef
      calves aged 4 to 6 mo and weighing 297 to 392 kg were randomly assigned to
      receive either 1) 0.5 mg/kg lactose monohydrate placebo (PLBO; n = 6), 2) 0.5
      mg/kg MEL (n = 6), or 3) 0.5 mg/kg MEL combined with 15 mg/kg GABA (MEL-GABA; n =
      6) once daily for 4 d. The first treatment was administered 4 h after a chemical
      synovitis/arthritis was induced with injection of 15 mg amphotericin B into the
      left hind lateral distal interphalangeal joint. Changes in activity were
      evaluated continuously with pedometers. Contact force, contact area, contact
      pressure, impulse, and stride length were recorded once daily with a pressure mat
      and visual lameness scores were determined by a masked observer using a 5-point
      scale. Cortisol and drug concentrations were determined daily by immunoassay and
      HPLC-mass spectrometry, respectively. Outcomes were compared statistically using
      a random effects mixed model and analysis of covariance. There was a positive
      association between lameness scores and serum cortisol concentrations (P = 0.02)
      and a negative association between lameness score and step count (P < 0.0001),
      total force (P = 0.001), force applied to the lateral claw (P = 0.02), contact
      pressure (P = 0.005), and impulse of the lateral claw (P = 0.01). Step count was
      greater in MEL calves compared with PLBO (P = 0.008) and MEL-GABA (P = 0.04)
      calves. Impulse was greater in the MEL-GABA calves compared with the PLBO calves
      (P = 0.03). There was an inverse relationship between plasma MEL concentrations
      and lameness score (P = 0.02) and a positive association between MEL
      concentrations and force applied to the lateral claw (P = 0.03), total contact
      pressure (P = 0.03), and impulse on the lateral claw (P = 0.02). There was a
      tendency towards a positive association between GABA concentrations, total
      impulse, and impulse on the lateral claw (P = 0.08) and a negative associate
      between GABA concentrations and step count (P = 0.08). The results of this study
      suggest that MEL administered alone or in combination with GABA reduced the
      severity of lameness in calves following induction of lameness with amphotericin
      B. These findings have implications for developing analgesic protocols in lame
      calves that address both production and welfare concerns.

PMID- 24664570
TI  - Effects of residual feed intake classification and method of alfalfa processing
      on ewe intake and growth.
AB  - The objective of this research was to evaluate the effects of residual feed
      intake (RFI) determined under ad libitum feeding conditions on DMI and
      performance of yearling ewes fed either chopped or pelleted alfalfa hay. In Exp.
      1, 45 ewe-lambs had ad libitum access to a pelleted grower diet for 63 d and
      individual DMI was determined using an electronic feed delivery system. Residual
      feed intake values were assigned to each ewe-lamb as a measure of feed
      efficiency. Sixteen ewe-lambs with the most positive RFI values were classified
      as high RFI (inefficient) and 16 ewe-lambs with the most negative RFI values were
      classified as low RFI (efficient). In Exp. 2, half of the ewes from each
      efficiency group were placed into 1 of 2 pens and provided ad libitum access to
      either pelleted or chopped alfalfa hay. Individual DMI was again determined using
      an electronic feed delivery system. Body weight, LM area (LMA), and 12th-rib back
      fat thickness (BF) were measured at the beginning and end of both experiments. In
      Exp. 1, DMI by ewe-lambs in the low RFI group was 9% less (P = 0.01) than by ewe
      lambs in the high RFI group (2.21 vs. 2.43 kg/d); however, ADG and initial and
      final BW, LMA, and BF did not differ (P > 0.27) among RFI groups. In Exp. 2,
      there were no feed processing * RFI group interactions (P > 0.14) for any trait.
      By design, RFI values were lower (P < 0.01) by yearling ewes in the low than high
      RFI group (-0.27 vs. 0.27); however, RFI values did not differ (P = 1.0) between
      yearling ewes fed chopped versus pelleted alfalfa. Dry matter intake was 22% less
      (P < 0.01) by yearling ewes in the low than high RFI group (2.5 vs. 3.2 kg/d) and
      59% less (P < 0.01) by yearling ewes fed chopped versus pelleted alfalfa (2.2 vs.
      3.5 kg/d). Initial and final BW, ADG, and G:F did not differ (P > 0.45) between
      RFI groups but were greater (P < 0.01) by yearling ewes fed pelleted alfalfa
      compared to chopped alfalfa. Final LMA did not differ (P = 0.77) between RFI
      groups, but final BF tended to be greater (P = 0.06) for high than low RFI
      yearling ewes (0.63 vs. 0.57 cm). Final LMA and BF were greater (P < 0.01) by
      yearling ewes fed pelleted than chopped alfalfa. Low RFI ewes had lower DMI and
      BF compared to high RFI ewes. Ewe efficiency as determined by RFI was repeatable
      on subsequent forage based diets; however, differences in intake and efficiency
      were more apparent when alfalfa was pelleted. 

PMID- 24664571
TI  - Effects of dietary ractopamine hydrochloride and zilpaterol hydrochloride
      supplementation on performance, carcass traits, and carcass cutability in beef
      steers.
AB  - British * Continental steers (initial BW = 484.6 kg) were fed at a commercial
      feed yard to evaluate the effects of beta-agonists on live performance, carcass
      characteristics, and carcass subprimal yield. Weights and ultrasonic measurements
      were used to allocate steers to pens (n = 40) divided equally into 4 blocks, with
      2 treatment replicates per block. Pens were randomly assigned to 1 of 5
      treatments: control; ractopamine-HCl (RH) fed at 200 or 300 mg * steer(-1) * d(
      1), or 400 mg * steer(-1) * d(-1) top dress for the final 30 d of feeding; or
      zilpaterol-HCl (ZH) fed at 7.5 mg/kg beginning 23 d before slaughter with a 3-d
      withdrawal period. Steers were harvested by block at a commercial facility over 4
      wk. Carcass based performance measures were calculated using initial pen weights
      and actual DMI. From each pen, eight carcasses that were within +/- 13.6 kg of
      the mean pen HCW were selected such that two carcasses were within each of the
      following four Yield Grade (YG) ranges: YG <= 2.8; 2.9-3.2; 3.3-3.5; YG > 3.5.
      Carcasses were fabricated by plant personnel to determine subprimal yield. Steers
      fed ZH had higher carcass-based ADG and carcass-based G:F compared with all other
      treatments (P < 0.05). Carcass-based ADG and carcass-based G:F were higher in RH
      treatments compared with controls (P < 0.05). Steers fed ZH had higher dressing
      percentages (1.0 to 1.6%) and larger LM area (4.3 to 6.7 cm(2)) than all other
      treatments (P < 0.05). Use of RH 400 and ZH increased HCW 6.3 and 11.1 kg,
      respectively compared with controls (P < 0.05). Compared with controls, RH 300
      and ZH decreased marbling score and the frequency of carcasses qualifying for
      upper 2/3 Choice premiums (P < 0.05). Beta-agonists increased subprimal yield
      from the round and loin; however, blade meat was the only cut from the rib or
      chuck affected by beta-agonists. Results from this study indicated improvements
      in performance and carcass traits as a result of beta-agonist use; however,
      differences between ZH, RH 400, and RH 300 treatments were minimal for carcass
      traits and cutability. Increases in saleable yield following beta-agonist use
      were not uniformly distributed across the four major primals and the majority of
      weight gain occurred in the lower priced cuts of the round and chuck. Increased
      response of the lower priced cuts to beta-agonists could have economic
      implications to packers.

PMID- 24664572
TI  - Crista galli mucocele: endoscopic marsupialization via frontoethmoid approach.
AB  - BACKGROUND: We report the first report of an expansile crista galli (CG) mucocele
      treated surgically by an endoscopic endonasal approach. Only 1 other case of a CG
      mucocele has been previously reported in the literature. This was treated by a
      craniotomy approach. CASE REPORT: We describe the technique employed in
      endoscopic marsupialization. We also discuss relevant CG anatomy, pneumatization
      patterns, surgical approaches, and its potential to cause disease, including CG
      sinusitis and mucocele formation. CONCLUSION: We present this case to highlight
      that the growing experience with endoscopic techniques offer us less morbid and
      more functional alternatives to a variety of lesions that were once tackled by
      neurosurgical or external approaches. In the contemporary era, the indications
      for open approaches and craniotomy for frontal sinus and CG lesions is likely
      limited. We recommend these patients undergo careful evaluation by a surgeon
      experienced in advanced endoscopic techniques before being advised to undergo
      open or craniotomy techniques.

PMID- 24664573
TI  - Substitution effects on the formation of T-shaped palladium carbene and
      thioketone complexes from Li/Cl carbenoids.
AB  - The preparation of palladium thioketone and T-shaped carbene complexes by
      treatment of thiophosphoryl substituted Li/Cl carbenoids with a Pd(0) precursor
      is reported. Depending on the steric demand, the anion-stabilizing ability of the
      silyl moiety (by negative hyperconjugation effects) and the remaining negative
      charge at the carbenic carbon atom, isolation of a three-coordinate, T-shaped
      palladium carbene complex is possible. In contrast, insufficient charge
      stabilization results in the transfer of the sulfur of the thiophosphoryl moiety
      and thus in the formation of a thioketone complex. While the thioketones are
      stable compounds the carbene complexes are revealed to be highly reactive and
      decompose under elimination of Pd metal. Computational studies revealed that both
      complexes are formed by a substitution mechanism. While the ketone turned out to
      be the thermodynamically favored product, the carbene is kinetically favored and
      thus preferentially formed at low reaction temperatures. 

PMID- 24664575
TI  - Publication output in the field of Public Health and its appreciation at
      political level in Austria.
AB  - In a pilot study, we aimed to identify the output of public health research by
      Austrian university and non-university research institutions and compare it with
      its translation into Austrian public health policy. A keyword search in PubMed
      was conducted for the period 2000 to 2013. The 'Public Health Newsletter'
      published by the Austrian Ministry of Health and the 'Health Reform Law 2013'
      were used as surrogate indicators for the translation of research into public
      health policy.A total of 97 publications in peer-reviewed journals showed a wide
      variation in topics. Comparing the research topics with the articles of the
      'Public Health Newsletter', we found identity in the field of communicable
      diseases. The Health Reform Law 2013 confirms the importance of evidence-based
      decision-making; yet, it contains no direct mentioning of or relation to research
      results. Based on our methodology, moderate appreciation of research results at
      the political level could be found in Austria. 

PMID- 24664574
TI  - Sarcoidosis vs. Sarcoid-like reactions: The Two Sides of the same Coin?
AB  - Differentiating between sarcoidosis as an autonomous disease and sarcoid-like
      reactions requires considerable efforts. The epithelioid cell granuloma is not
      equivalent to sarcoidosis because it may be identified in a number of infectious
      and noninfectious disorders, including neoplastic diseases. At the current state
      of knowledge, accurate distinction between different causes of epithelioid cell
      granulomas is in many cases not possible. Despite being characteristic of
      sarcoidosis and sarcoid-like reactions, the epithelioid cell granuloma is not
      their synonym, as numerous other causes can give rise to such a type of
      granulomatous infiltrate. Its etiology should be sought through careful
      additional investigations, including the genetic signature of both
      conditions.Sarcoid-like reactions may be grouped generally into several subtypes.
      The differentiation between each one of them requires a certain combination of
      diagnostic tests. The major objective of these tests is to exclude or to prove
      the presence of an infectious, tumoral, or immunogenic antigen on the one hand,
      and to characterize the genetic profile of the affected patients (for example,
      sarcoidosis-specific genes) on the other. Only thus may one accurately
      differentiate between the two pathologic conditions described earlier in the
      abstract.The clear differentiation between sarcoidosis as a separate disease and
      sarcoid-like pathologies leads to the more precise clarification of the final
      diagnosis, which may in turn allow for a more appropriate therapy and improvement
      in the quality of life of the patients. Equating sarcoid granulomas with
      sarcoidosis can lead to serious consequences in a number of patients. Sadly
      enough, after scrutinizing the current available data in the world literature,
      one cannot find criteria to allow such distinction in a high percentage of the
      investigated cases.This critical review provides a completely new pathogenetic
      and diagnostic algorithm, helping in the differentiation between the disease
      sarcoidosis and the sarcoid-like pathologies with different etiology. An update
      on the inclusion criteria from the ATS/ERS/WASOG (American Thoracic
      Society/European Respiratory Society/World Association of Sarcoidosis and other
      Granulomatous Disorders) statement (which at the current state of knowledge seems
      to be ineffective) for the diagnosis of sarcoidosis is also suggested.In
      conclusion, molecular mimicry may be seen as the main pathogenic generator not
      only of sarcoidosis but also of sarcoid-like reactions. A completely new and
      exact definition of the notion of or the sarcoidosis disease itself will be
      possible only after 1. defining the genetic risk for the development of
      sarcoidosis as an autonomous disease and supplementing the sarcoidosis consensus
      of ATS/ERS/WASOG from 1999 with this important information, and 2. defining the
      notion of a sarcoid-like reaction and its subforms. 

PMID- 24664576
TI  - Volumetric R2 * mapping using z-shim multi-echo gradient echo imaging.
AB  - PURPOSE: To introduce macroscopic B0 field inhomogeneity-compensated volumetric
      R2 * mapping method with a three-dimensional (3D) z-shim multi-echo acquisition.
      METHODS: The proposed z-shim sequence acquired conventional and z-shimmed echoes
      alternately with bipolar readout gradients. A constant-valued z-shim gradient was
      applied prior to each negative readout gradient lobe. A phase combination
      algorithm was also proposed based on this pulse sequence, which acquires a B0
      inhomogeneity-compensated field map that was shown to play a critical role for
      accurate R2 * mapping. A modified signal model based on recently suggested model
      for 3D acquisition was proposed for R2 * quantification. RESULTS: To validate the
      performance of the proposed method, phantom and in vivo experiments were
      performed and compared with other methods. An increase in the range of field
      inhomogeneity correction was shown in the phantom results. For in vivo studies,
      the proposed method showed enhanced R2 * map quality for the different subjects.
      CONCLUSION: The proposed method improves R2 * estimation, especially in the
      frontal and temporal regions.

PMID- 24664577
TI  - Gemella parahaemolysans sp. nov. and Gemella taiwanensis sp. nov., isolated from
      human clinical specimens.
AB  - Four Gram-staining-positive, catalase-negative, coccoid isolates, designated
      NTUH_1465(T), NTUH_2196, NTUH_4957 and NTUH_5572(T), were isolated from human
      specimens. The four isolates displayed more than 99.6% 16S rRNA gene sequence
      similarity with Gemella haemolysans ATCC 10379(T), and 96.7 to 98.6% similarity
      with Gemella sanguinis ATCC 700632(T), Gemella morbillorum ATCC 27824(T) or
      Gemella cuniculi CCUG 42726(T). However, phylogenetic analysis of concatenated
      sequences of three housekeeping genes, groEL, rpoB and recA, suggested that the
      four isolates were distinct from G. haemolysans ATCC 10379(T) and other species.
      Isolates NTUH_2196, NTUH_4957 and NTUH_5572(T) clustered together and formed a
      stable monophyletic clade. DNA-DNA hybridization values among strains
      NTUH_1465(T) and NTUH_5572(T) and their phylogenetically related neighbours were
      all lower than 49%. The four isolates could be distinguished from G. haemolysans
      and other species by phenotypic characteristics. Based on the phylogenetic and
      phenotypic results, two novel species Gemella parahaemolysans sp. nov. (type
      strain NTUH_1465(T) = BCRC 80365(T) = JCM 18067(T)) and Gemella taiwanensis sp.
      nov. (type strain NTUH_5572(T) = BCRC 80366(T) = JCM 18066(T)) are proposed.

PMID- 24664578
TI  - Hoppeia youngheungensis gen. nov., sp. nov., a member of the Flavobacteriaceae
      isolated from tidal flat sediment, and emended descriptions of the genus
      Sediminibacter and Sediminibacter furfurosus.
AB  - A Gram-reaction-negative, proteorhodopsin-containing, yellow-pigmented, rod
      shaped, non-gliding and strictly aerobic bacterium, designated strain YIK12(T),
      was isolated from tidal flat sediment of Yeongheung Island at the coast of the
      West Sea of Korea. Cells produced non-diffusible carotenoid pigments, but not
      flexirubin-type pigment. Phylogenetic analyses based on 16S rRNA gene sequences
      indicated that the isolate was affiliated to the family Flavobacteriaceae and
      showed highest similarity to Sediminibacter furfurosus MAOS-86(T) (93.3%). Growth
      was observed at 24-44  degrees C (optimum 30  degrees C), at pH 6.5-8.0 (optimum
      7.0) and in the presence of 1.5-7.0% sea salts (optimum 2%). The DNA G+C content
      was 40.4 mol% and the predominant cellular fatty acids were iso-C(15 : 0), iso
      C(15 : 1) G, iso-C(17 : 0) 3-OH, iso-C(16 : 0) 3-OH, anteiso-C(15 : 0) and iso
      C(15 : 0) 3-OH. The major respiratory quinone was MK-6. On the basis of data from
      the present polyphasic taxonomic study, strain YIK12(T) is considered to
      represent a novel species of a new genus in the family Flavobacteriaceae, for
      which the name Hoppeia youngheungensis gen. nov., sp. nov. is proposed. The type
      strain of H. youngheungensis is YIK12(T) ( = KCCM 43023(T) = JCM 19488(T)).
      Emended descriptions of the genus Sediminibacter and Sediminibacter furfurosus
      are given.

PMID- 24664579
TI  - Bradyrhizobium paxllaeri sp. nov. and Bradyrhizobium icense sp. nov., nitrogen
      fixing rhizobial symbionts of Lima bean (Phaseolus lunatus L.) in Peru.
AB  - A group of strains isolated from root nodules of Phaseolus lunatus (Lima bean) in
      Peru were characterized by genotypic, genomic and phenotypic methods. All strains
      possessed identical 16S rRNA gene sequences that were 99.9% identical to that of
      Bradyrhizobium lablabi CCBAU 23086(T). Despite having identical 16S rRNA gene
      sequences, the Phaseolus lunatus strains could be divided into two clades by
      sequence analysis of recA, atpD, glnII, dnaK and gyrB genes. The genome sequence
      of a representative of each clade was obtained and compared to the genomes of
      closely related species of the genus Bradyrhizobium. Average nucleotide identity
      values below the species circumscription threshold were obtained when comparing
      the two clades to each other (88.6%) and with all type strains of the genus
      Bradyrhizobium (<=92.9%). Phenotypes distinguishing both clades from all
      described and closely related species of the genus Bradyrhizobium were found. On
      the basis of the results obtained, two novel species, Bradyrhizobium paxllaeri
      sp. nov. (type strain LMTR 21(T) = DSM 18454(T) = HAMBI 2911(T)) and
      Bradyrhizobium icense sp. nov. (type strain LMTR 13(T) = HAMBI 3584(T) = CECT
      8509(T) = CNPSo 2583(T)), are proposed to accommodate the uncovered clades of
      Phaseolus lunatus bradyrhizobia. These species share highly related but distinct
      nifH and nodC symbiosis genes.

PMID- 24664580
TI  - Thalassomonas eurytherma sp. nov., a marine proteobacterium.
AB  - Two Gram-staining-negative, aerobic, rod-shaped bacterial strains, designated
      Za6a-12(T) and Za6a-17, were isolated from seawater of the East China Sea. Cells
      of Za6a-12(T) and Za6a-17 were approximately 1.5-2.0 um*0.5-0.7 um and motile by
      a single polar flagellum. Strains grew optimally at pH 7.5-8.0, 28  degrees C,
      and in the presence of 2.5-3.0% (w/v) NaCl. Chemotaxonomic analysis showed that
      the predominant respiratory quinone of strains Za6a-12(T) and Za6a-17 was
      ubiquinone-8 (>97%), and the major fatty acids were C(14 : 0), C(16 : 1)omega7c
      and/or iso-C(15 : 0) 2-OH, C(16 : 0) and C(17 : 1)omega8c. Their DNA G+C contents
      were 42.7 mol% and 42.8 mol%, respectively. 16S rRNA gene sequence analysis
      revealed that the isolates belonged to the genus Thalassomonas and showed the
      highest sequence similarity to Thalassomonas loyana CBMAI 722(T) (95.9%). Strains
      Za6a-12(T) and Za6a-17 could be differentiated from T. loyana CBMAI 722(T)
      according to their phenotypic and chemotaxonomic features, DNA G+C contents and
      fatty acid composition. On the basis of these features, we propose strains Za6a
      12(T) and Za6a-17 to be representatives of a novel species of the genus
      Thalassomonas with the name Thalassomonas eurytherma sp. nov. suggested. Strain
      Za6a-12(T) ( = CGMCC 1.12115(T) = JCM 18482(T)) is the type strain of this novel
      species.

PMID- 24664581
TI  - Expression of targeted ribozyme against telomerase RNA causes altered expression
      of several other genes in tumor cells.
AB  - Telomeres are tandem repeat sequences present at chromosome end that are
      synthesized by RNA-protein enzyme called telomerase. The RNA component (TR)
      serves as template for telomerase reverse transcriptase (TERT) for generating
      telomere repeats. TERT is overexpressed in actively dividing cells including
      cancerous cells, absent in differentiated somatic cells whereas human telomerase
      RNA (hTR) is present in normal as well as in cancer cells. Telomerase
      overexpression in cancer cells ensures telomere length maintenance that actually
      provides proliferative advantage to cells. Stable expression of ribozyme against
      hTR in HeLa cells results in reduction of hTR levels, telomerase activity, and
      telomere length which is accompanied by altered cell morphology and expression of
      several specific cellular genes. The altered genes deduced from differentially
      display PCR and 2D gel electrophoresis upon hTR knockdown have function in
      ribosome biogenesis, chromatin modulation, cell cycle control, and p63-dependant
      pathways. Our observations shows hTR participates in diverse cellular functions
      other than telomere maintenance, validates as a possible drug targets in p53- and
      pRB-negative status, and indicated possible cross-talks between telomerase and
      other cellular pathways. 

PMID- 24664582
TI  - Neutropenia and invasive fungal infection in patients with hematological
      malignancies treated with chemotherapy: a multicenter, prospective, non
      interventional study in China.
AB  - In this study, we explored the relationship between neutropenia (absolute
      neutrophil count (ANC) <1,500/mm(3)) and invasive fungal infection (IFI) in
      Chinese patients who had hematological malignancies treated with chemotherapy. We
      conducted a multicenter, prospective, non-interventional study of consecutive
      patients with hematological malignancies undergoing chemotherapy in China and
      determined clinical characteristics of patients who developed neutropenia and
      IFI. The results indicated that for the 2,177 neutropenic patients, 88 (4.0 %)
      were diagnosed with IFI. We found that a high risk of IFI (P<0.05) is associated
      with male gender, non-remission of the primary disease, use of two or more broad
      spectrum antibiotics, treatment with parenteral nutrition, presence of
      cardiovascular disease, history of IFI, and neutropenia. When the ANC was less
      than 1,000, 1,000~500, 500~100, and <100/mm(3), the incidence of IFI was 0.5,
      5.2, 3.9, and 4.7 %, respectively (ANC>1,000/mm(3) versus other groups, P<0.001).
      When the ANC was less than 1,000, 500, or 100/mm(3) for 10 days or more, the
      incidence of IFI was 3.2 versus 6.1 % (P=0.0052), 3.5 versus 7.1 % (P=0.0021),
      and 3.1 versus 10.0 % (P<0.001). When the ANC was less than 100/mm(3), taking
      antifungal prophylaxis reduced the incidence of IFI (P<0.05). The IFI
      attributable mortality rate was 11.7 %. In conclusion, Chinese patients with IFI,
      severe and prolonged neutropenia increases the incidence of IFI. The incidence of
      IFI associated with neutropenia was reduced when antifungal prophylaxis was
      given. IFI was associated with a significantly increased high mortality rate in
      hematological malignancy patients with neutropenia.

PMID- 24664583
TI  - High-mobility group nucleosome-binding domain 5 increases drug resistance in
      osteosarcoma through upregulating autophagy.
AB  - Although tumor therapy has been improved in the past decades, the survival
      outcomes for osteosarcoma remain unsatisfactory, and one of the primary reasons
      for the failure of current treatment is that patients with late-stage cancer
      often develop resistance to anticancer drugs. High-mobility group nucleosome
      binding domain 5 (HMGN5) is a newly identified gene associated with cancer and
      autophagy, which could inhibit apoptosis induced by anticancer agents. However,
      it is still unclear whether HMGN5 regulated autophagy in osteosarcoma, and the
      mechanism and significance of HMGN5-mediated autophagy in tumor therapy is never
      investigated. In this study, we first detected HMGN5 in vivo and in vitro. HMGN5
      was highly expressed in osteosarcoma tumor, especially in posttreatment tumor.
      Next, we employed adenovirus-mediated overexpression of HMGN5 in U-2OS and MG63
      to investigate the role of HMGN5 in osteosarcoma cell lines. Adenovirus-mediated
      overexpression of HMGN5 could efficiently upregulate the expression level of
      HMGN5 in osteosarcoma cell lines at both messenger RNA (mRNA) and protein levels.
      Anticancer agents namely doxorubicin, cisplatin, and methotrexate each induced
      HMGN5 upregulation in human U-2OS and MG63 osteosarcoma cell lines. In addition,
      overexpression of HMGN5 reduced the chemosensitivity of osteosarcoma cells in
      vitro, and the mechanistic investigation revealed that HMGN5 increased drug
      resistance by upregulating autophagy. Therefore, HMGN5 is a critical factor in
      the development of chemoresistance through regulating autophagy, and it offers a
      novel target for improving osteosarcoma therapy. 

PMID- 24664584
TI  - NEDD9 overexpression correlates with poor prognosis in gastric cancer.
AB  - In this study, the expression of neural precursor cell expressed developmentally
      downregulated 9 (NEDD9) in benign and malignant gastric tissues was investigated,
      and the significance of NEDD9 in gastric cancer prognosis was explored.
      Immunohistochemistry was used to detect NEDD9 expression in gastric cancer,
      nontumor gastric, and normal gastric tissues. The relationship between NEDD9
      expression in gastric cancer tissues and the clinicopathologic factors was
      examined using the Mann-Whitney U test. The two factors between NEDD9 expression
      and tumor node metastasis (TNM) stage in gastric cancer patients were analyzed by
      Spearman rank correlation analysis. The Kaplan-Meier method and log-rank test
      were used to compare the overall survival of NEDD9 negative, weak positive
      expression, and strong positive expression group. NEDD9 expression rates were
      significantly higher (P < 0.001) in gastric cancer tissues (162 out of 187, 86.6
      %) compared with normal (2 out of 11, 18.2 %) and nontumor (11 out of 58, 19.0 %)
      gastric tissues. The upregulated NEDD9 expression in gastric cancer tissue was
      significantly correlated with high preoperative CEA level (P = 0.044), poor
      differentiation (P = 0.007), tissue invasion (P = 0.015), present lymph node
      metastasis (P < 0.001), and high TNM stage (P < 0.001). NEDD9 expression was
      positively correlated with clinical TNM stage. Advancing clinical TNM stage
      corresponded with higher NEDD9 expression (r s = 0.289, P < 0.001). The overall 5
      year survival of gastric cancer patients with strong positive NEDD9 expression
      was significantly shorter compared with the survival of NEDD9 negative and weakly
      positive expression group. NEDD9 may be used as a biomarker in the clinical
      setting to predict the prognosis of gastric cancer patients.

PMID- 24664585
TI  - Prognostic role of circulating microRNA-21 in cancers: evidence from a meta
      analysis.
AB  - Circulating microRNAs (miRNAs) exhibit altered expression in patients with cancer
      and could be considered as potential prognostic biomarker of cancer. Here, we
      performed a meta-analysis to summarize all the results from available studies,
      aiming to analyze the prognostic role of circulating microRNA-21 (miR-21) in
      human cancers. Eligible studies were identified from PubMed and EMBASE through
      multiple search strategies. We extracted and estimated the hazard ratios (HRs)
      for overall survival (OS), which compared the high and low expression levels of
      circulating miR-21 in patients with a variety of carcinomas. Pooled HRs and 95 %
      confidence intervals (CIs) were calculated. Eleven studies with a total of 1,224
      patients with various carcinomas were included this meta-analysis. For OS, higher
      circulating miR-21 expression could significantly predict worse outcome with the
      pooled HR of 2.11 (95 % CI 1.36-3.26, P = 0.0009). The subgroup analysis
      suggested that the elevated circulating miR-21 expression was correlated with
      worse OS in Asian population with the pooled HR of 2.36 (95 % CI 1.61-3.48, P <
      0.0001) and digestive system cancers with the pooled HR of 2.19 (95 % CI 1.01
      4.75, P = 0.05). The present meta-analysis suggests that circulating miR-21
      expression is associated with poor survival in patients with cancer and could be
      a prognostic biomarker for those patients.

PMID- 24664586
TI  - Comment on Gu et al. entitled "Prognostic significance of HER2 expression based
      on trastuzumab for gastric cancer (ToGA) criteria in gastric cancer: an updated
      meta-analysis".

PMID- 24664587
TI  - Chromosomal rearrangements in patients with clinical features of Silver-Russell
      syndrome.
AB  - Silver-Russell syndrome (SRS) is characterized by pre- and postnatal growth
      retardation, relative macrocephaly, asymmetry, and a triangular facial gestalt.
      In 5-10% of the patients the phenotype is caused by maternal UPD 7, and 38-64% of
      the patients present with hypomethylation at the imprinting center region 1
      (ICR1) on 11p15.5. The etiology of the remaining cases is so far not known and
      various (sub-)microscopic chromosome aberrations with a phenotype resembling SRS
      have been published, especially duplication 11p15 (n = 15), deletion 12q14 (n =
      19), ring chromosome 15, deletion 15qter, and various other mostly unique
      chromosomal aberrations (n = 30). In this study the phenotypes of these
      chromosomal aberrations were revisited and compared with the phenotypes of
      maternal UPD 7 and hypomethylation at ICR1 on 11p15.5. In some patients with a
      unique chromosomal aberration even the hallmarks of SRS were missing. Patients
      with duplication 11p15 show a more variable occipitofrontal head circumference at
      birth, a higher frequency of intellectual disability, and additional anomalies
      not reported in SRS. Deletion 12q14 is characterized by less severe pre- and
      postnatal growth retardation and less impressive relative macrocephaly. Patients
      with ring chromosome 15 and deletion 15qter have no relative macrocephaly (mostly
      even microcephaly) and more severe intellectual disability. Finally, deletion
      15qter lacks the triangular facial gestalt. In summary, as SRS seems not an
      adequate diagnosis in many of these patients, diagnosis should focus on the
      chromosomal aberration than on SRS.

PMID- 24664588
TI  - Effect of training on corticomotor excitability in clinical neck pain.
AB  - BACKGROUND: Corticomotor excitability has been shown to correlate with motor
      learning and functional recovery. The aim of the present study was to monitor
      changes in excitability of the corticomotor pathways induced by neck training and
      to compare the effects in patients with neck or knee pain and pain-free
      participants. METHODS: Corticomotor excitability was assessed using transcranial
      magnetic stimulation and electromyography at baseline, after 30 min and 1 h, and
      at a 1-week follow-up visit. The primary outcome measures were changes in
      amplitudes and latencies of motor evoked potentials (MEPs) at 1-week follow-up.
      RESULTS: MEP responses induced by neck training yielded significantly different
      outcomes in the three groups. In the group with neck pain and training, MEP
      amplitudes were significantly reduced between baseline and 30 min (p <= 0.05),
      but with no significant difference between baseline, 1 h (p = 0.178) and 1 week
      (p = 0.067). In the group with knee pain and training, MEP amplitudes
      significantly increased between baseline and 30 min (p <= 0.01) and 1 h (p <
      0.001), but not after 1 week (p = 0.524) compared with baseline. In the pain-free
      group, there were no changes over time. CONCLUSION: Neck training reduced
      neuroplastic responsiveness of corticomotor pathways in neck pain patients in
      contrast to knee pain patients and pain-free participants. Increased attention to
      adaptive and maladaptive neuroplastic responses induced by training may prove
      valuable in the process of optimizing clinical outcomes.

PMID- 24664589
TI  - Programmable photo-electrochemical hydrogen evolution based on multi-segmented
      CdS-Au nanorod arrays.
AB  - Programmable photocatalysts for hydrogen evolution have been fabricated based on
      multi-segmented CdS-Au nanorod arrays, which exhibited high-efficiency and
      programmability in hydrogen evolution as the photoanodes in the
      photoelectrochemical cell. Multiple different components each possess unique
      physical and chemical properties that provide these cascade nanostructures with
      multiformity, programmability, and adaptability. These advantages allow these
      nanostructures as promising candidates for high efficient harvesting and
      conversion of solar energy. 

PMID- 24664590
TI  - Can the world afford to eliminate congenital rubella?

PMID- 24664591
TI  - Mimicking bubble use in nature: propulsion of Janus particles due to hydrophobic
      hydrophilic interactions.
AB  - Bubbles are widely used by animals in nature in order to fulfill important
      functions. They are used by animals in order to walk underwater or to stabilize
      themselves at the water/air interface. The main aim of this work is to imitate
      such phenomena, which is the essence of biomimetics. Here, bubbles are used to
      propel and to control the location of Janus particles in an aqueous medium. The
      synthesis of Janus SiO2-Ag and polystyrene-Ag (PS-Ag) particles through embedment
      in Parafilm is presented. The Janus particles, partially covered with
      catalytically active Ag nanoparticles, are redispersed in water and placed on a
      glass substrate. The active Ag sites are used for the splitting of H2O2 into
      water and oxygen. As a result, an oxygen bubble is formed on one side of the
      particle and promotes its propulsion. Once formed, the bubble-particle complex is
      stable and therefore, can be manipulated by tuning hydrophilic-hydrophobic
      interactions with the surface. In this way a transition between two- and three-
      dimensional motion is possible by changing the hydrophobicity of the substrate.
      Similar principles are used in nature.

PMID- 24664593
TI  - An efficient alternative marker for specific identification of Mycobacterium
      tuberculosis.
AB  - Rapid and accurate identification of mycobacteria to the species level is
      important to provide epidemiological information and to guide the appropriate
      treatment, especially identification of the Mycobacterium tuberculosis (MTB)
      which is the leading pathogen causing tuberculosis. The genetic marker named as
      Mycobacterium tuberculosis specific sequence 90 (mtss90) was screened by a
      bioinformatics software and verified by a series of experiments. To test its
      specificity, 266 strains of microorganisms and human cells were used for the
      mtss90 conventional PCR method. Moreover, the efficiency of mtss90 was evaluated
      by comparing 16S rDNA (Mycobacterium genus-specific), IS6110 (specific
      identification of MTB complex), mtp40 (MTB-specific) and PNB/TCH method
      (traditional bacteriology testing) in Mycobacterium strains. All MTB isolates
      were mtss90 positive. No amplification was observed from any other tested strains
      with M. microti as an exception. Compared with the traditional PNB/TCH method,
      the coincidence rate was 99.1 % (233/235). All of the mtss90 positive strains
      were IS6110 and 16S rDNA positive, indicating a 100 % coincidence rate (216/216)
      between mtss90 and these two genetic markers. Additionally, mtss90 had a better
      specificity than mtp40 in the identification of MTB. Lastly, a real-time PCR
      diagnostic assay was developed for the rapid identification of MTB. In
      conclusion, mtss90 may be an efficient alternative marker for species-specific
      identification of MTB and could be used for the diagnosis of tuberculosis
      combined with other genetic markers.

PMID- 24664594
TI  - Digital necrosis revealing giant cell arteritis.

PMID- 24664592
TI  - Evening primrose oil and celecoxib inhibited pathological angiogenesis,
      inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of
      angiopoietin-1.
AB  - Rheumatoid arthritis is a chronic inflammatory disease characterized by
      overproduction of inflammatory mediators along with undermined oxidative
      defensive mechanisms. Pathological angiogenesis was found to play a critical role
      in the progression of this disease. The current study was carried out to evaluate
      the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening
      primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in
      combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis
      was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the
      right hind paw of male albino rats. All treatments were administered orally from
      day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till
      day 27 after CFA injection. In the arthritic group, the results revealed
      significant decrease in the body weight and increase in ankle circumference,
      plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-alpha) levels.
      Anti-oxidant status was suppressed as manifested by significant decline in
      reduced glutathione content along with decreased enzymatic activity of superoxide
      dismutase and increased lipid peroxidation. Oral administration of EPO exerted
      normalization of body weight, ANG-1, and TNF-alpha levels with restoration of
      activity as shown by reduced malondialdehyde levels. Moreover, histopathological
      examination demonstrated that EPO significantly reduced the synovial hyperplasia
      and inflammatory cells invasion in joint tissues, an effect that was enhanced by
      combination with aspirin or celecoxib. The joint use of GLA-rich natural oils,
      which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities,
      with traditional analgesics represents a promising strategy to restrain the
      progression of rheumatoid arthritis. 

PMID- 24664595
TI  - Spanish medical students' attitudes and views towards mental health and
      psychiatry: a multicentric cross-sectional study.
AB  - OBJECTIVE: The aim of this study is to investigate the attitudes towards mental
      illness and psychiatry among fifth year Spanish medical students. METHODS: The
      study included 171 students from three medical schools located in different areas
      of Spain: Cadiz; UCA (n = 113), Madrid; San Pablo-CEU (n = 22), and Barcelona;
      UAB (n = 36). They responded, prior to their undergraduate medical course in
      psychiatry, to the AMI questionnaire to measure the attitudes towards mental
      illness and to Balon's adapted questionnaire to investigate their view towards
      psychiatry. RESULTS: The students (93.4 %) had a positive attitude towards mental
      illness (AMI). Attitudes towards psychiatry were fairly positive with a few
      negative views, specifically regarding the role of psychiatrists (items 11 and
      13) and the prestige of the specialty (item 16). There were some statistically
      significant differences between the three medical schools in the perception of
      psychiatry as a medical discipline. A better attitude towards mental illness was
      associated with a better view of the overall merits of psychiatry. CONCLUSIONS:
      Findings suggest that Spanish medical students do not have a negative attitude
      towards mental illness and they have a good perception of psychiatry, although
      there are still some misconceptions about this specialty. These student's
      attitudes could favor an appropriate management of patients suffering from mental
      illness.

PMID- 24664596
TI  - The Calendar, Complementarity, Pacing, and Service Delivery in the College Mental
      Health Setting.
AB  - The author comments on the effect of the academic calendar on demand for mental
      health services. 

PMID- 24664597
TI  - Status of general medicine training and education in psychiatry residency.
AB  - OBJECTIVE: With the current emphasis on integrated care, the role of
      psychiatrists is expanding to either directly provide medical care or coordinate
      its delivery. The purpose of this study was to survey general psychiatry programs
      on the extent of general medicine training provided during residency. METHODS: A
      short web-based survey was sent to 173 residency program directors to recruit
      participants for a larger survey. Thirty-seven participants were recruited and
      surveyed, and of these, 12 (32.4%) responded. The survey assessed the extent of
      general medicine training and didactics during and after the first postgraduate
      year and attitudes towards enhancing this training in residency. This study was
      approved by the local institutional review board. RESULTS: Seventy-five percent
      of programs require only the minimum 4 months of primary care in the first
      postgraduate year, and didactics during these months is often not relevant to
      psychiatry residents. Some programs offer elective didactics on chronic medical
      conditions in the fourth postgraduate year. Respondents are in favor of enhancing
      general medicine training in psychiatry but indicate some resistance from their
      institutions. CONCLUSIONS: These results suggest that very few programs require
      additional clinical training in relevant medical illnesses after the first
      postgraduate year. Respondents indicated favorable institutional support for
      enhancing training, but also expected resistance. The reasons for resistance
      should be an area of future research. Also important is to determine if enhancing
      medical didactics improves patient care and outcomes. The changing role of
      psychiatrists entails a closer look at resident curricula.

PMID- 24664598
TI  - Building connections through teletechnologies to augment resident training in
      psychodynamic psychotherapy.
AB  - OBJECTIVE: This report describes the utilization of teletechnologies for training
      in psychodynamic psychotherapy in a residency training program. This includes the
      development of a unique psychodynamic psychotherapy case conference for
      residents, education in a particular model of short-term dynamic psychotherapy
      through distance education, and the use of web-based technologies to provide
      individual case supervision. METHODS: Evaluation forms and verbal feedback from
      trainees have been used as a preliminary evaluation of this program. RESULTS:
      Experience with educational models using web-based technologies have greatly
      enhanced the learning experience for residents beginning training in
      psychodynamic psychotherapy CONCLUSION: Web-based technologies can be used
      effectively to augment resources in a residency training program and might be
      considered to link programs to share resources.

PMID- 24664599
TI  - Parameters of training, academic involvement, and practice setting predictive of
      retention in combined medical-psychiatric practice.
AB  - OBJECTIVE: The authors contrasted physicians trained in both psychiatry and
      another specialty who continue to practice both specialties vs. those who
      practice only psychiatry, in terms of their training, academic profile, and
      practice setting. METHOD: The authors analyzed survey responses from 132 doubly
      boarded physicians who vary in whether or not they continue to practice both
      specialties. Group results were compared using chi square, Fisher exact, and t
      tests. RESULTS: Of graduates of double-board programs, 79.2% continue in dual
      practice. Other factors associated with continued combined practice were training
      in neurology-psychiatry, greater academic involvement, high motivation, practice
      in a non-public hospital setting, and demonstrated leadership capacity.
      CONCLUSION: Double-board training programs have been successful in producing a
      group of clinicians committed to long-term combined medical-psychiatric practice,
      but this effect is stronger in psychiatry-neurology than in other types of
      combined practice. Future research should investigate other practice parameters
      that foster or impede integrated medical-psychiatric care.

PMID- 24664600
TI  - Supervising the tearful trainee: opportunities for professional growth and
      learning.
AB  - Trainees in psychiatry sometimes become tearful during supervision, and this
      presents the supervisor with significant challenges and also opportunities for
      the development of professionalism. This paper describes two major anxieties of
      trainees: first, that they will be unable to control their feelings during their
      clinical work and that this will derail the fulfillment of their duties; second,
      that that their feelings stem from an identification with some aspect of the
      patient or the patient's circumstances and may fear that this exposes them to the
      stigma of mental illness. The author describes how the trainee's potential for
      shame can be greatly mitigated by supervisory interventions that treat this as a
      'teachable' moment and opportunity for growth in professionalism. The author
      outlines effective interventions including didactic instruction and education,
      role modeling of empathic connection in the context of a boundaried relationship,
      and sensitive referral to mental health services for unresolved emotional issues
      or psychiatric symptoms. Suggestions of specific wording of interventions are
      provided throughout. 

PMID- 24664601
TI  - What is the prevalence of the experience of death of a patient by suicide among
      medical students and residents? A systematic review.
AB  - OBJECTIVE: The purposes of this study were to examine the literature on the
      proportion of medical students and residents who experience the death of a
      patient by suicide and to identify curricula with data on outcomes that assist
      medical students or residents in preparing for or managing the psychological
      stress in dealing with those suicides. METHODS: The authors searched PubMed,
      Scopus, Google Scholar, and ScienceDirect databases using search terms patient
      suicide, trainee, medical student, and resident. They conducted a separate search
      to identify relevant curricula using the same terms in combination with coping,
      teaching, programs, and education. RESULTS: Eight studies met inclusion criteria,
      all of which concerned psychiatry residents alone. We found no studies that
      determined the prevalence of the experience of death of a patient by suicide
      among medical students or residents in specialties other than psychiatry. The
      prevalences were 31, 33, 43, 47, 54, 61, 68, and 69 %. All studies were cross
      sectional, and none collected data prospectively. Limitations of these data
      included single-site studies, lack of clarity of the specific question asked, low
      response rates, and uncertain reporting periods. The authors found two curricula
      with outcome data that assisted medical trainees in managing the psychologically
      distressing consequences of the death of a patient. CONCLUSION: Although the data
      are limited, psychiatry residents commonly experience the death of a patient by
      suicide. There is a paucity of data on this topic concerning the experiences of
      medical students and of residents in other specialties.

PMID- 24664602
TI  - A national survey of medical student suicides.
AB  - OBJECTIVE: Because there is no current information on medical student suicides,
      the authors surveyed US medical schools about deaths by suicide of medical
      students from June 2006 to July 2011. METHODS: In spring through summer of 2012,
      the authors sent electronic surveys to the 133 accredited US allopathic medical
      schools at the time, excluding Puerto Rican schools. The 15-item survey included
      questions about deaths by suicide and deaths by means other than suicide. In the
      case of a reported suicide, the survey obtained information regarding demographic
      characteristics and method of suicide. RESULTS: The 90 responding schools
      (response rate 69 %) reported a total of six suicides (four males, two females;
      five Caucasians, one Asian) from July 2006 to June 2011. Two deaths by suicide
      occurred in first year, two in second year, and two in third year. Two of the
      suicides occurred by gunshot, two by hanging, one by overdose, and for one, the
      cause of death was unknown. Three of the six students left a suicide note.
      CONCLUSION: Although the number and rate of suicides among medical students may
      be lower than a prior survey that was conducted more than 15 years ago, these
      data affirm the importance of suicide prevention programs for medical students.

PMID- 24664603
TI  - Personalized normative feedback for depression symptoms: a qualitative pilot
      study of female undergraduates.
AB  - OBJECTIVE: This pilot study explored students' responses to feedback about their
      own and their peers' depression symptoms. The study also examined how experiences
      with the normative feedback might vary according to academic exposure to
      depression-related topics. METHODS: For 9 weeks, female undergraduates (N=73)
      completed a weekly web-based version of the 8-item Patient Health Questionnaire,
      which gauges depression symptom levels. Next, they participated in semi
      structured face-to-face interviews where they responded to the personalized
      normative feedback. The interviews were transcribed, coded, and analyzed.
      RESULTS: Students responded favorably to the feedback and without notable
      distress. The feedback increased students' awareness of their own depression
      symptoms and those of their peers. Those with higher academic exposure to
      depression-related topics were more likely to have accurate perceptions of their
      peers' depression symptoms and were less likely to be surprised by information in
      the feedback than students with less exposure. CONCLUSIONS: Personalized
      normative feedback for depression symptoms has potential as an effective tool for
      promoting more accurate views of personal and peer depression symptoms and
      reducing barriers to help-seeking. Students with less academic exposure to
      depression-related topics may benefit from increased knowledge of how to gauge
      their own depression symptoms and increased awareness of their peers' symptoms.
      Further research is needed to more fully evaluate the effects of this feedback
      and to directly assess the effects of this feedback on help-seeking behaviors.

PMID- 24664604
TI  - Creating Opportunities for Organizational Leadership (COOL): Creating a culture
      and curriculum that fosters psychiatric leadership development and quality
      improvement.
AB  - The authors describe the Harvard South Shore Psychiatry Residency Training
      Program curriculum "Creating Opportunities for Organizational Leadership," an
      innovative, multitiered, resident-driven, outcome-focused set of experiences
      designed to develop residents' leadership skills in personal leadership,
      organizational leadership, negotiation, strategic thinking, and systems redesign.

PMID- 24664605
TI  - Helping psychiatry residents cope with patient suicide.
AB  - OBJECTIVE: Every clinical specialty has its own high risk patient challenges that
      threaten to undermine their trainees' professional identity, evolving sense of
      competence. In psychiatric training, it is patient suicide, an all-too frequently
      encountered consequence of severe mental illness that may leave the treating
      resident perplexed, guilt-ridden, and uncertain of their suitability for the
      profession. This study evaluates a patient suicide training program aimed at
      educating residents about patient suicide, common reactions, and steps to
      attenuate emotional distress while facilitating learning. METHODS: The
      intervention was selected aspects of a patient suicide educational program,
      "Collateral Damages,"-video vignettes, focused discussions, and a patient-based
      learning exercise. Pre- and post-survey results were compared to assess both
      knowledge and attitudes resulting from this educational program. Eight psychiatry
      residency training programs participated in the study, and 167 of a possible 240
      trainees (response rate = 69.58 %) completed pre- and post-surveys. RESULTS:
      Knowledge of issues related to patient suicide increased after the program.
      Participants reported increased awareness of the common feelings physicians and
      trainees often experience after a patient suicide, of recommended "next" steps,
      available support systems, required documentation, and the role played by risk
      management. CONCLUSIONS: This patient suicide educational program increased
      awareness of issues related to patient suicide and shows promise as a useful and
      long overdue educational program in residency training. It will be useful to
      learn whether this program enhances patient care or coping with actual patient
      suicide. Similar programs might be useful for other specialties.

PMID- 24664607
TI  - The ADMSEP Education Scholars Program: a novel approach to cultivating
      scholarship among psychiatry educators.
AB  - The author describes the Association of Directors of Medical Student Education in
      Psychiatry's Education Scholars Program, a 2-year longitudinal, guided mentorship
      program, anchored by didactic instruction in the fundamental concepts of
      educational scholarship.

PMID- 24664606
TI  - Teaching psychiatry to undergraduates: peer-peer learning using a "GP letter".
AB  - OBJECTIVE: The authors describe a novel peer-peer learning activity with medical
      students, encompassing a specialist psychiatrist-general practitioner (GP) dyadic
      interchange of letters, and a group discussion facilitated by a GP and a
      psychiatrist to enhance students' appreciation of the complexities of psychiatric
      assessment and formulation, emphasize the importance of the GP in the
      comprehensive longitudinal care of people with a mental illness, and improve
      students' written communication skills. METHODS: Quantitative and qualitative
      methods were employed to evaluate the activity. RESULTS: Twenty-eight fifth-year
      medical students undertook the learning activity; of these, 20 completed the
      questionnaires and 18 participated in the focus groups. Quantitative feedback was
      good, with most agreeing or strongly agreeing that the activity met the learning
      objectives. The qualitative outcomes suggested the students found the exercise
      relevant and useful in clarifying their communication style regarding a patient
      with a psychiatric problem. CONCLUSIONS: The use of peer-peer learning using a
      "GP letter" can go some way towards meeting a number of teaching and learning
      challenges pertinent to psychiatry.

PMID- 24664608
TI  - Psychiatry resident outpatient clinic supervision: how training directors are
      balancing patient care, education, and reimbursement.
AB  - OBJECTIVE: Recent literature on psychiatry resident outpatient clinic supervision
      is sparse. In designing outpatient supervision, training directors must balance
      optimization of patient care, education, and reimbursement. The authors sought to
      describe current practices for supervision within psychiatry resident outpatient
      clinics. METHODS: Directors of US psychiatric residency training programs were
      surveyed to examine methods used for supervision and billing in psychiatry
      resident outpatient clinics. RESULTS: Seventy of 183 (38%) training directors
      responded. Most programs utilize live supervision for medication management
      visits, but psychotherapy supervision is more varied. Billing practices are
      variable among programs. CONCLUSIONS: This report is intended to help training
      directors consider options for optimizing patient care and resident education in
      their outpatient clinics, while maintaining financial solvency. Ultimately,
      programs should have a way of ensuring all patient cases have some form of
      ongoing supervision, with possible modification based on training level, resident
      ability, patient acuity, and appointment type.

PMID- 24664610
TI  - Opportunities and challenges: residents' perspectives on the next accreditation
      system in psychiatry.

PMID- 24664609
TI  - Global health training in US graduate psychiatric education.
AB  - OBJECTIVE: Global health training opportunities have figured prominently into
      medical students' residency program choices across a range of clinical
      specialties. To date, however, the national scope of global mental health
      education has not heretofore been systematically assessed. We therefore sought to
      characterize the distribution of global health training opportunities in US
      graduate psychiatric education. METHODS: We examined the web pages of all US
      psychiatry residency training programs, along with search results from a
      systematic Google query designed to identify global health training
      opportunities. RESULTS: Of the 183 accredited US psychiatry residency programs,
      we identified 17 programs (9.3%) offering 28 global health training opportunities
      in 64 countries. Ten psychiatry residency programs offered their residents
      opportunities to participate in one or more elective-based rotations, eight
      offered research activities, and six offered extended field-based training. Most
      global health training opportunities occurred within the context of externally
      administered, institution-wide initiatives generally available to residents from
      a range of clinical specialties, rather than within internally administered
      departmental initiatives specifically tailored for psychiatry residents.
      CONCLUSIONS: There are relatively few global health training opportunities in US
      graduate psychiatric education. These activities have a clear role in enhancing
      mastery of Accreditation Council for Graduate Medical Education core
      competencies, but important challenges related to program funding and evaluation
      remain.

PMID- 24664611
TI  - Introduction and commentary on the psychiatry milestones.
AB  - OBJECTIVE: The Psychiatry Milestones are a major change in the accreditation of
      residency training and evaluation of residents and programs. This introduction
      provides an overview of the papers in this issue describing the Psychiatry
      Milestones and a commentary on the process of their development. METHODS: The
      author describes the challenges and experiences in creating the Psychiatry
      Milestones as a member of the Working Group and Advisory Group. RESULTS: While
      there were many potential obstacles in development, the Psychiatry Milestones
      were created due to the efforts of all those involved. CONCLUSION: The inclusive
      and participatory process was successful and serves as a model for the
      implementation and further development of the Psychiatry Milestones.

PMID- 24664612
TI  - Remediation practices in Canadian psychiatry clerkships.
AB  - OBJECTIVES: There is a lack of information regarding interventions for
      undergraduate students at Canadian medical schools who require remediation during
      their psychiatric training. The need for a theoretical framework to guide
      remediation has been identified. In this study, we sought to characterize
      remediation taking place in undergraduate psychiatry education, particularly
      during clerkship. A secondary goal was to ascertain whether those responsible for
      remediation were aware of the stages of change (transtheoretical) model, and
      whether they formally incorporated this framework (or another) into their
      remediation processes. METHODS: A short six-question survey on remediation
      practices was e-mailed to educators responsible for undergraduate psychiatry
      education at all 17 Canadian medical schools as identified through the Canadian
      Organization of Undergraduate Psychiatry Educators (COUPE). RESULTS: The response
      rate was 67 %. Respondents' overall impressions of their school's remediation
      process were that it was "highly effective" (25 %), or "somewhat effective" (67
      %); 8 % reported being unsure of its effectiveness. While 75 % of survey
      respondents were aware of the stages of change model, only 17 % reported using
      this framework: no alternate theoretical frameworks were reported. CONCLUSIONS:
      The most common form of evaluation was multiple-choice question (MCQ) exams, and
      the most common form of remediation was exam rewrites. There is little
      information regarding the long-term outcomes of remediation, and further research
      would be useful in formulating recommendations regarding best practices.

PMID- 24664613
TI  - Co-ordination of growth, gas exchange and hydraulics define the carbon safety
      margin in tree species with contrasting drought strategies.
AB  - Gas exchange, growth, water transport and carbon (C) metabolism diminish during
      drought according to their respective sensitivities to declining water status.
      The timing of this sequence of declining physiological functions may determine
      how water and C relations compromise plant survival. In this paper, we test the
      hypothesis that the degree of asynchrony between declining C supply
      (photosynthesis) and C demand (growth and respiration) determines the rate and
      magnitude of changes in whole-plant non-structural carbohydrates (NSC) during
      drought. Two complementary experiments using two tree species (Eucalyptus
      globulus Labill. and Pinus radiata D. Don) with contrasting drought response
      strategies were performed to (i) assess changes in radial stem growth,
      transpiration, leaf water potential and gas exchange in response to chronic
      drought, and (ii) evaluate the concomitant impacts of these drought responses on
      the temporal patterns of NSC during terminal drought. The three distinct phases
      of water stress were delineated by thresholds of growth cessation and stomatal
      closure that defined the 'carbon safety margin' (i.e., the difference between
      leaf water potential when growth is zero and leaf water potential when net
      photosynthesis is zero). A wider C safety margin in E. globulus was defined by an
      earlier cessation of growth relative to photosynthesis that reduced the demand
      for NSC while maintaining C acquisition. By contrast, the narrower C safety
      margin in P. radiata was characterized by a synchronous decline in growth and
      photosynthesis, whereby growth continued under a declining supply of NSC from
      photosynthesis. The narrower C safety margin in P. radiata was associated with
      declines in starch concentrations after ~ 90 days of chronic drought and
      significant depletion of starch in all organs at mortality. The observed
      divergence in the sensitivity of drought responses is indicative of a potential
      trade-off between maintaining hydraulic safety and adequate C availability.

PMID- 24664614
TI  - X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic
      insights from an international patient registry.
AB  - The web-based Ectodermal Dysplasia International Registry (EDIR) is a
      comprehensive patient-reported survey contributing to an understanding of
      ectodermal dysplasia (ED). XLHED is the most common of the genetic ED syndromes
      and was the primary diagnosis reported by 223/835 respondents (141 males and 82
      females). Overall, 96% of XLHED registrants reported as least one other affected
      family member and 21% reported a family history of infant or childhood deaths,
      consistent with the published mortality data in this disorder. In general, XLHED
      is diagnosed by the triad of decreased sweating, reduced hair, and hypodontia
      (present in 89%, 74%, and 74% of XLHED respondents). Additionally, the registry
      dataset confirmed a spectrum of life-long XLHED clinical complications including
      recurrent sinus infections (49% males, 52% females), nasal congestion often foul
      smelling and interfering with feeding (73% males, 27% females), eczema (66%
      males, 40% females), wheezing (66% males, 45% females), and a hoarse, raspy voice
      (67% males, 23% females). The Registry results also highlighted features
      consistently differentiating XLHED from the non-hypohidrotic ED syndromes
      including the frequency of infant/childhood deaths, the presence of limb/digit
      abnormalities, feeding issues related to nasal discharge, dentures, and a
      diagnosis of asthma. These results represent the largest collection of data on a
      broad-spectrum of health-related issues affecting ED patients. This project
      provides information for expanding knowledge of the natural history of XLHED, and
      as such may facilitate the diagnosis and treatment of its varied and lifelong
      medical challenges.

PMID- 24664615
TI  - Who benefits from diabetes self-management interventions? The influence of
      depression in the Latinos en Control trial.
AB  - BACKGROUND: Depressive symptoms are common among adults with diabetes. Depression
      and social support may influence diabetes self-management. PURPOSE: This study
      aimed to examine change in depressive symptoms and the role of depression and
      support on clinical and dietary outcomes among Latinos with type 2 diabetes
      participating in a diabetes self-management intervention. METHODS: Participants
      (N = 252) were randomized to the intervention or usual care. Mixed effects models
      were used to examine interaction effects between intervention status and
      depressive symptoms (Centers for Epidemiologic Studies Depression (CES-D) score)
      and support for diabetes self-management behaviors at baseline. Outcomes were
      measured at baseline and 4 and 12 months and included dietary quality, physical
      activity, depressive symptoms, and hemoglobin A1c levels. RESULTS: Intervention
      participants had lower CES-D scores at follow-up than control participants. An
      interaction effect between intervention status and CES-D scores predicted diet
      quality. CONCLUSION: Latinos with depressive symptoms may derive the greatest
      benefits from diabetes self-management interventions. Additional research on
      support during diabetes self-management interventions is warranted.

PMID- 24664616
TI  - Nickel(I) monomers and dimers with cyclopentadienyl and indenyl ligands.
AB  - The reaction of (MU-Cl)2Ni2(NHC)2 (NHC = 1,3-bis(2,6-diisopropylphenyl)-1,3
      dihydro-2H-imidazol-2-ylidene (IPr) or 1,3-bis(2,6-diisopropylphenyl)imidazolidin
      2-ylidene (SIPr)) with either one equivalent of sodium cyclopentadienyl (NaCp) or
      lithium indenyl (LiInd) results in the formation of diamagnetic NHC supported
      Ni(I) dimers of the form (MU-Cp)(MU-Cl)Ni2(NHC)2 (NHC = IPr (1 a) or SIPr (1 b);
      Cp = C5H5) or (MU-Ind)(MU-Cl)Ni2(NHC)2 (NHC = IPr (2 a) or SIPr (2 b); Ind =
      C7H9), which contain bridging Cp and indenyl ligands. The corresponding reaction
      between two equivalents of NaCp or LiInd and (MU-Cl)2Ni2(NHC)2 (NHC = IPr or
      SIPr) generates unusual 17 valence electron Ni(I) monomers of the form (eta(5)
      Cp)Ni(NHC) (NHC = IPr (3 a) or SIPr (3 b)) or (eta(5)-Ind)Ni(NHC) (NHC = IPr (4
      a) or SIPr (4 b)), which have nonlinear geometries. A combination of DFT
      calculations and NBO analysis suggests that the Ni(I) monomers are more strongly
      stabilized by the Cp ligand than by the indenyl ligand, which is consistent with
      experimental results. These calculations also show that the monomers have a lone
      unpaired-single-electron in their valence shell, which is the reason for the
      nonlinear structures. At room temperature the Cp bridged dimer (MU-Cp)(MU
      Cl)Ni2(NHC)2 undergoes homolytic cleavage of the Ni-Ni bond and is in equilibrium
      with (eta(5)-Cp)Ni(NHC) and (MU-Cl)2Ni2(NHC)2. There is no evidence that this
      equilibrium occurs for (MU-Ind)(MU-Cl)Ni2(NHC)2. DFT calculations suggest that a
      thermally accessible triplet state facilitates the homolytic dissociation of the
      Cp bridged dimers, whereas for bridging indenyl species this excited triplet
      state is significantly higher in energy. In stoichiometric reactions, the Ni(I)
      monomers (eta(5)-Cp)Ni(NHC) or (eta(5)-Ind)Ni(NHC) undergo both oxidative and
      reductive processes with mild reagents. Furthermore, they are rare examples of
      active Ni(I) precatalysts for the Suzuki-Miyaura reaction. Complexes 1 a, 2 b, 3
      a, 4 a and 4 b have been characterized by X-ray crystallography.

PMID- 24664617
TI  - Determinants of optimal mastectomy skin flap thickness.
AB  - BACKGROUND: There is a limited evidence base to guide surgeons on the ideal
      thickness of skin flaps during mastectomy. Here the literature relevant to
      optimizing mastectomy skin flap thickness is reviewed, including anatomical
      studies, oncological considerations, factors affecting viability, and the impact
      of surgical technique and adjuvant therapies. METHODS: A MEDLINE search was
      performed using the search terms 'mastectomy' and 'skin flap' or 'flap
      thickness'. Titles and abstracts from peer-reviewed publications were screened
      for relevance. RESULTS: A subcutaneous layer of variable thickness that contains
      minimal breast epithelium lies between the dermis and breast tissue. The
      thickness of this layer may vary within and between breasts, and does not appear
      to be associated with obesity or age. The existence of a distinct layer of
      superficial fascia in the breast remains controversial and may be present in only
      up to 56 per cent of patients. When present, it may not be visible
      macroscopically, and can contain islands of breast tissue. As skin flap necrosis
      occurs in approximately 5 per cent of patients, a balance must be sought between
      removing all breast tissue at mastectomy and leaving reliably viable skin flaps.
      CONCLUSION: The variable and unpredictable thickness of the breast subcutaneous
      layer means that a single specific universal thickness for mastectomy skin flaps
      cannot be recommended. It may be that the plane between the subdermal fat and
      breast parenchyma is a reasonable guide for mastectomy flap thickness, but this
      may not always correspond to a subcutaneous fascial layer.

PMID- 24664618
TI  - Bilateral juvenile nasopharyngeal angiofibroma: report of a case.
AB  - BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is the most common benign
      neoplasm of the nasopharynx. Almost always unilateral on diagnosis, JNAs are
      locally invasive and may extend across the midline, giving a false bilateral
      appearance; as such, true bilateral JNA is exceedingly rare. We present a recent
      case of true bilateral JNA. METHODS: Single case report of a patient with
      bilateral JNA, including clinical presentation, diagnosis, and management.
      RESULTS: The patient presented with unilateral nasal obstruction and recurrent
      epistaxis. Computed tomography and magnetic resonance imaging demonstrated
      bilateral, noncontiguous masses. Angiography revealed independent vascular
      supplies from each respective side with no bilateral supply noted. The patient
      underwent preoperative embolization followed by endoscopic surgical removal of
      the larger mass; no complications were noted. Follow-up at 2 years demonstrated
      no recurrence or growth. CONCLUSION: The vast majority of JNAs are unilateral,
      though invasive growth to the contralateral side may appear "bilateral" in
      presentation. Proper identification of true bilateral JNA is helpful in guiding
      management, wherein excision of both tumors may not be necessary.

PMID- 24664620
TI  - Efficacy of liraglutide in a real-life cohort.
AB  - INTRODUCTION: In the Liraglutide Effect and Action in Diabetes (LEAD) randomized
      clinical trials (RCTs) assessing liraglutide in type 2 diabetes mellitus (T2DM),
      glycated hemoglobin (A1c) was reduced by 7-16 mmol/mol and weight by up to 3.4
      kg. As real-life efficacy data on liraglutide is limited, the authors assessed
      clinical effects in a real-life cohort. METHODS: In this retrospective analysis
      from the Israeli Health Maintenance Organization Maccabi, of patients with T2DM,
      treated with liraglutide >=6 months during 2011-2012, evaluations were performed
      at baseline and 6 months. RESULTS: Insulin-naive patients (n = 1,101) treated
      with liraglutide with at least one A1c or weight measurement were identified. In
      933 patients with an additional A1c value after 6 months, A1c decreased by 9
      mmol/mol (p < 0.0001, 95% CI 7-11) from 72 mmol/mol. In patients receiving >2
      oral antidiabetic drugs (OADs) prior to liraglutide treatment (80.7% patients),
      A1c decreased by 7 mmol/mol, and in those receiving <=2 OADs, by 12 mmol/mol. In
      453 patients with baseline data available, weight decreased by 2.55 kg (p <
      0.0001); 173 patients (38.18%) achieved >=1% A1c reduction. Furthermore, 91
      patients (20.1%) achieved National Institute for Health and Care Excellence
      (NICE) criteria (decreased A1c >=1%; weight >=3%). Weight reduction was
      marginally correlated with A1c reduction. CONCLUSIONS: Evidence from real-life
      use of liraglutide demonstrated clinical effects similar to those demonstrated in
      RCTs.

PMID- 24664621
TI  - Compensating for magnetic field inhomogeneity in multigradient-echo-based MR
      thermometry.
AB  - PURPOSE: MR thermometry (MRT) is a noninvasive method for measuring temperature
      that can potentially be used for radio frequency (RF) safety monitoring. This
      application requires measuring absolute temperature. In this study, a
      multigradient-echo (mGE) MRT sequence was used for that purpose. A drawback of
      this sequence, however, is that its accuracy is affected by background gradients.
      In this article, we present a method to minimize this effect and to improve
      absolute temperature measurements using MRI. THEORY: By determining background
      gradients using a B0 map or by combining data acquired with two opposing readout
      directions, the error can be removed in a homogenous phantom, thus improving
      temperature maps. METHODS: All scans were performed on a 3T system using ethylene
      glycol-filled phantoms. Background gradients were varied, and one phantom was
      uniformly heated to validate both compensation approaches. Independent
      temperature recordings were made with optical probes. RESULTS: Errors correlated
      closely to the background gradients in all experiments. Temperature distributions
      showed a much smaller standard deviation when the corrections were applied (0.21
      degrees C vs. 0.45 degrees C) and correlated well with thermo-optical probes.
      CONCLUSION: The corrections offer the possibility to measure RF heating in
      phantoms more precisely. This allows mGE MRT to become a valuable tool in RF
      safety assessment.

PMID- 24664619
TI  - Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes:
      a systematic review and mixed treatment comparison.
AB  - OBJECTIVE: To compare the safety and efficacy of the dipeptidylpeptidase-4 (DPP
      4) inhibitors in patients with type 2 diabetes and inadequate glycemic control.
      DESIGN: Systematic review of randomized controlled trials (RCTs), health economic
      evaluation studies, systematic reviews, and meta-analyses, followed by primary
      Bayesian mixed treatment comparison meta-analyses (MTCs), and secondary
      frequentist direct-comparison meta-analyses using a random-effects model.
      Outcomes were reported as weighted mean change from baseline, or odds ratio (OR)
      with 95% credible interval. DATA SOURCES: MEDLINE, MEDLINE In-Process, EMBASE,
      and BIOSIS via Dialog ProQuest; Cochrane Central Register of Controlled Trials
      and Cochrane Database of Systematic Reviews via EBSCO; four diabetes and two
      technical congress abstracts; and health technology assessment organization
      websites. ELIGIBILITY CRITERIA: Patients with type 2 diabetes and inadequate
      glycemic control receiving any pharmacological anti-diabetic treatment. DATA
      EXTRACTION AND ANALYSIS: Title/abstracts were reviewed for eligibility, followed
      by full-text review of publications remaining after first pass. A three-person
      team filtered articles and an independent reviewer checked a random selection
      (10%) of filtered articles. Data extraction and quality assessment of studies
      were also independently reviewed. Five DPP-4 inhibitors (alogliptin, linagliptin,
      saxagliptin, sitagliptin, and vildagliptin) were compared via meta-analysis
      (where data were available) as monotherapy, dual therapy (plus metformin,
      sulfonylurea, pioglitazone, or insulin), and triple therapy (plus
      metformin/sulfonylurea). RESULTS: The review identified 6,601 articles; 163 met
      inclusion criteria and 85 publications from 83 RCTs contained sufficient or
      appropriate data for analysis. MTCs demonstrated no differences between DPP-4
      inhibitors in mean change from baseline in glycosylated hemoglobin (HbA1c) or
      body weight, or the proportions of patients achieving HbA1c <7% or experiencing a
      hypoglycemic event, apart from in patients on alogliptin plus metformin, who
      achieved HbA1c <7% more frequently than those treated with saxagliptin plus
      metformin [OR 6.41 (95% CI 3.15-11.98) versus 2.17 (95% CI 1.56-2.95)].
      CONCLUSIONS: This systematic review and MTC showed similar efficacy and safety
      for DPP-4 inhibitors as treatment for type 2 diabetes, either as monotherapy or
      combination therapy.

PMID- 24664623
TI  - A predictive tool to estimate the risk of axillary metastases in breast cancer
      patients with negative axillary ultrasound.
AB  - BACKGROUND: Sentinel node biopsy (SNB) is the "gold standard" in axillary staging
      in clinically node-negative breast cancer patients. However, axillary treatment
      is undergoing a paradigm shift and studies are being conducted on whether SNB may
      be omitted in low-risk patients. The purpose of this study was to evaluate the
      risk factors for axillary metastases in breast cancer patients with negative
      preoperative axillary ultrasound. METHODS: A total of 1,395 consecutive patients
      with invasive breast cancer and SNB formed the original patient series. A
      univariate analysis was conducted to assess risk factors for axillary metastases.
      Binary logistic regression analysis was conducted to form a predictive model
      based on the risk factors. The predictive model was first validated internally in
      a patient series of 566 further patients and then externally in a patient series
      of 2,463 patients from four other centers. All statistical tests were two-sided.
      RESULTS: A total of 426 of the 1,395 (30.5 %) patients in the original patient
      series had axillary lymph node metastases. Histological size (P < 0.001),
      multifocality (P < 0.001), lymphovascular invasion (P < 0.001), and palpability
      of the primary tumor (P < 0.001) were included in the predictive model. Internal
      validation of the model produced an area under the receiver operating
      characteristics curve (AUC) of 0.731 and external validation an AUC of 0.79.
      CONCLUSIONS: We present a predictive model to assess the patient-specific
      probability of axillary lymph node metastases in patients with clinically node
      negative breast cancer. The model performs well in internal and external
      validation. The model needs to be validated in each center before application to
      clinical use.

PMID- 24664625
TI  - Internal mammary sentinel lymph node biopsy: minimally invasive staging and
      tailored internal mammary radiotherapy.

PMID- 24664624
TI  - Regional chemotherapy for unresectable intrahepatic cholangiocarcinoma: a
      potential role for dynamic magnetic resonance imaging as an imaging biomarker and
      a survival update from two prospective clinical trials.
AB  - BACKGROUND: For patients with unresectable intrahepatic cholangiocarcinoma (ICC),
      treatment options are limited and survival is poor. This study summarizes the
      long-term outcome of two previously reported clinical trials using hepatic
      arterial infusion (HAI) with floxuridine and dexamethasone (with or without
      bevacizumab) in advanced ICC. METHODS: Prospectively collected clinicopathologic
      and survival data were retrospectively reviewed. Response was based on Response
      Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion
      data correlated with outcome. RESULTS: Forty-four patients were analyzed
      (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3
      months, 41 patients had died of disease. Partial response by RECIST was observed
      in 48 %, and 50 % had stable disease. Three patients underwent resection after
      response, and 82 % received additional HAI after removal from the trials. Median
      survival was similar in both trials (floxuridine 29.3 months vs.
      floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived >=3
      years, including 5 (11 %) who survived >=5 years. Tumor perfusion measured on pre
      treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s
      (AUC90 and AUC180, respectively)] was significantly higher in >=3-year survivors
      and was the only factor that distinguished this group from <3-year survivors
      (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p
      = 0.003, respectively). Median hepatic progression-free survival was longer in
      >=3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008). CONCLUSIONS:
      HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI
      DCE-MRI may predict treatment outcome.

PMID- 24664626
TI  - Perioperative risk assessment for gastrectomy by surgical apgar score.
AB  - BACKGROUND: Recently, a simple and easy complication prediction system, the
      surgical apgar score (SAS) calculated by three intraoperative parameters
      (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has
      been proposed for general surgery. In this study, we evaluated the predictability
      of the original SAS (oSAS) for severe complications after gastrectomy. In
      addition, the predictability of a modified SAS (mSAS) was evaluated, in which the
      cutoff value for blood loss was slightly modified. METHODS: We investigated 328
      patients who underwent gastrectomy at the Shizuoka Cancer Center in 2010.
      Clinical data, including intraoperative parameters, were collected
      retrospectively. Patients with postoperative morbidities classified as Clavien
      Dindo grade IIIa or more were defined as having severe complications. Univariate
      and multivariate analyses were performed to elucidate factors that affected the
      development of severe complications. RESULTS: Thirty-six patients (11.0 %) had
      severe complications postoperatively. Univariate analyses showed that the oSAS (p
      = 0.007) and mSAS (p < 0.001), as well as sex, preoperative chemotherapy, cStage,
      type of operation, thoracotomy, surgical approach, operation time, and extent of
      lymph node dissection, were associated with severe complications. Multivariate
      analysis showed that an mSAS <=6 was found to be an independent risk factor for
      severe complication, while an oSAS <=6 was not. CONCLUSIONS: The oSAS was not
      found to be a predictive factor for severe complications following gastrectomy in
      Japanese patients. A slightly modified SAS (i.e. the mSAS) is considered to be a
      useful predictor for the development of severe complications in elective surgery.

PMID- 24664627
TI  - High responsivity and gate tunable graphene-MoS2 hybrid phototransistor.
AB  - A 2D atomic-layer-thickness phototransistor based on a graphene-MoS2 bybrid
      device is constructed with a photoresponse much larger than that of individual
      graphene or MoS2 based phototransistors. Strong and selective light absorption in
      the MoS2 layer creates electric charges that are transferred to graphene layers
      derived by a build-in electrical field, where they recirculate many times due to
      the high carrier mobility of graphene. Gate tunable Fermi level in graphene layer
      allows the responsivity of this hybrid phototransistor to be continuously tuned
      from 0 to about 10(4) mA/W by the gate voltage. Furthermore, large scale,
      flexible, and transparent 2D phototransistors with high responsivity are
      constructed from the CVD-grown graphene and MoS2 flakes. The high responsivity,
      gate-tunable sensitivity, wavelength selectivity, and compatibility with current
      circuit technologies of this type device give it great potential for future
      application in integrated nano-optoelectronic systems. 

PMID- 24664628
TI  - Benchmark study on glyphosate-resistant crop systems in the United States.
      Economics of herbicide resistance management practices in a 5 year field-scale
      study.
AB  - BACKGROUND: Since the introduction of glyphosate-resistant (GR) crops, growers
      have often relied on glyphosate-only weed control programs. As a result, multiple
      weeds have evolved resistance to glyphosate. A 5 year study including 156 growers
      from Illinois, Iowa, Indiana, Nebraska, North Carolina and Mississippi in the
      United States was conducted to compare crop yields and net returns between grower
      standard weed management programs (SPs) and programs containing best management
      practices (BMPs) recommended by university weed scientists. The BMPs were
      designed to prevent or mitigate/manage evolved herbicide resistance. RESULTS:
      Weed management costs were greater for the BMP approach in most situations, but
      crop yields often increased sufficiently for net returns similar to those of the
      less expensive SPs. This response was similar across all years, geographical
      regions, states, crops and tillage systems. CONCLUSIONS: Herbicide use strategies
      that include a diversity of herbicide mechanisms of action will increase the long
      term sustainability of glyphosate-based weed management strategies. Growers can
      adopt herbicide resistance BMPs with confidence that net returns will not be
      negatively affected in the short term and contribute to resistance management in
      the long term.

PMID- 24664629
TI  - Electrodermal responses and memory recall in migraineurs and headache-free
      controls.
AB  - BACKGROUND: Chronic pain patients show increased peripheral activity when exposed
      to stimuli relevant to their pain problem. It has been suggested that in migraine
      there is a highly specific conditioning or sensitization to pain stimuli. The
      aims of this study were to analyse whether migraineurs (1) are sensitive not only
      to pain-related but also to other negative emotional words; and (2) show a memory
      bias for pain words, when compared to headache-free controls. METHODS: Sixty-six
      adults participated in the study ( X  = 27 years; SD = 7). They observed 30 words
      (pain or negative emotional or neutral) in a pseudo-randomized order.
      Subsequently, participants were asked to recall the words presented during the
      trial. RESULTS: Skin conductance responses (SCRs) induced by pain descriptors and
      emotional words were very similar to each other and significantly larger than
      those induced by neutral words; however, there were no differences between both
      groups in SCRs. Significant differences in immediate memory recall were found
      between the two groups: migraineurs recalled more emotional words than controls.
      CONCLUSIONS: The findings suggest that in migraine, not only pain-related but
      also negative emotional words may act as triggers. These outcomes may have
      therapeutic implications as interventions could target problematic pain-related
      memories that influence migraine pain perception and pain-related physiological
      responses.

PMID- 24664630
TI  - Malaria and anaemia in pregnancy: a cross-sectional study of pregnant women in
      rural communities of Southeastern Nigeria.
AB  - BACKGROUND: Several strategies are used in the care of pregnant women accessing
      antenatal care in primary health centres in Nigeria, with the aim of reducing the
      burden of malaria and anaemia. The objective of the study was to appraise the
      prevalence of malaria parasitaemia and anaemia in pregnant women attending
      antenatal clinics in rural communities of Southeastern Nigeria where malaria
      preventive strategies are in place. METHODS: We undertook a cross-sectional study
      of 300 pregnant women receiving antenatal care in randomly selected primary
      health centres in the Nkanu West local government area (LGA), Enugu state,
      Nigeria from August to September 2010. RESULTS: The prevalence of malaria
      parasitaemia was 92.0% (276/300) (mild in 86.7% [260/300] and moderate in 15.3%
      [16/300]). The prevalence of anaemia was 49.3% (148/300) (mild in 29.3% [88/300]
      and moderate in 20% [60/300]). There were no severe cases of malaria parasitaemia
      or anaemia. The educational status and occupation of participants were
      significantly associated with the occurrence of peripheral parasitaemia and
      anaemia respectively (p<0.05). CONCLUSION: The prevalence of malaria and anaemia
      is very high in the Nkanu West LGA of Enugu State, Nigeria. Efforts to reduce the
      prevalence of malaria parasitaemia and anaemia in pregnancy should be intensified
      in rural settings of Enugu state and Nigeria as a whole.

PMID- 24664631
TI  - Urinary angiotensinogen as a potential biomarker of intrarenal renin-angiotensin
      system activity in Chinese chronic kidney disease patients.
AB  - BACKGROUND: Urinary angiotensinogen (AGT) mainly derives from the AGT produced in
      proximal tubular cells. Evidence exists that supports the correlation between
      urinary AGT and circulating AGT. AIM: To investigate the role of urinary AGT as a
      potential biomarker of intrarenal renin-angiotensin system activity in Chinese
      chronic kidney disease (CKD) patients. METHODS: ELISA-based method used to
      quantify urinary AGT. Analyzed the relationship between urinary AGT and
      intrarenal angiotensin II (Ang II) activity in 128 CKD patients. ELISA was
      applied to measure the urinary and plasma renin activity, AGT, Ang II and
      aldosterone. Furthermore expression levels of intrarenal renin, AGT, Ang II and
      Ang II receptor were examined by immunohistochemistry staining (IHCS) in 72 CKD
      patients undergoing renal biopsy. RESULTS: The logarithmic transformation
      Log(urinary AGT/UCre) levels showed a normal distribution. Therefore, Log(urinary
      AGT/UCre) levels were used for the analyses. Average urinary AGT was 2.02 +/-
      0.55 ng/(mg Cr). Hypertension, urinary protein, urinary Ang II and urinary type
      IV collagen (Col IV) positively correlated with urinary AGT. Estimated glomerular
      filtration rate (eGFR), urinary sodium and serum AGT negatively correlated with
      urinary AGT. Multiple regression analysis indicated that low serum AGT, high
      urinary protein, urinary Ang II and urinary Col IV correlated significantly with
      high urinary AGT. CONCLUSIONS: We observed positive correlation between urinary
      AGT and positive IHCS area of AGT, Ang II and Ang II type 1 receptor in renal
      tissue. These data suggest that urinary AGT might be a potential biomarker of
      intrarenal Ang II activity in CKD patients.

PMID- 24664632
TI  - High performance all-polymer solar cell via polymer side-chain engineering.

PMID- 24664633
TI  - Relationship between whole-body tumor burden, clinical phenotype, and quality of
      life in patients with neurofibromatosis.
AB  - Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis share a
      predisposition to develop multiple nerve sheath tumors. Previous studies have
      demonstrated that patients with NF1 and NF2 have reduced quality of life (QOL),
      but no studies have examined the relationship between whole-body tumor burden and
      QOL in these patients. We administered a QOL questionnaire (the SF-36) and a
      visual analog pain scale (VAS) to a previously described cohort of adult
      neurofibromatosis patients undergoing whole-body MRI. One-sample t-tests were
      used to compare norm-based SF-36 scores to weighted population means. Spearman
      correlation coefficients and multiple linear regression analyses controlling for
      demographic and disease-specific clinical variable were used to relate whole-body
      tumor volume to QOL scales. Two hundred forty-five patients (142 NF1, 53 NF2, 50
      schwannomatosis) completed the study. Subjects showed deficits in selected
      subscales of the SF-36 compared to adjusted general population means. In
      bivariate analysis, increased tumor volume was significantly associated with pain
      in schwannomatosis patients, as measured by the SF-36 bodily pain subscale (rho =
      -0.287, P = 0.04) and VAS (rho = 0.34, P = 0.02). Regression models for NF2
      patients showed a positive relationship between tumor burden and increased pain,
      as measured by the SF-36 (P = 0.008). Patients with NF1, NF2, and schwannomatosis
      suffer from reduced QOL, although only pain shows a clear relationship to
      patient's overall tumor burden. These findings suggest that internal tumor volume
      is not a primary contributor to QOL and emphasize the need for comprehensive
      treatment approaches that go beyond tumor-focused therapies such as surgery by
      including psychosocial interventions.

PMID- 24664634
TI  - Sexual knowledge and victimization in adults with autism spectrum disorders.
AB  - There is a significant gap in understanding the risk of sexual victimization in
      individuals with autism spectrum disorders (ASD) and the variables that
      contribute to risk. Age appropriate sexual interest, limited sexual knowledge and
      experiences, and social deficits, may place adults with ASD at increased risk.
      Ninety-five adults with ASD and 117 adults without ASD completed questionnaires
      regarding sexual knowledge sources, actual knowledge, perceived knowledge, and
      sexual victimization. Individuals with ASD obtained less of their sexual
      knowledge from social sources, more sexual knowledge from non-social sources, had
      less perceived and actual knowledge, and experienced more sexual victimization
      than controls. The increased risk of victimization by individuals with ASD was
      partially mediated by their actual knowledge. The link between knowledge and
      victimization has important clinical implications for interventions. 

PMID- 24664635
TI  - Relationships between feeding problems, behavioral characteristics and
      nutritional quality in children with ASD.
AB  - Many children with autism spectrum disorders (ASD) have co-occurring feeding
      problems. However, there is limited knowledge about how these feeding habits are
      related to other behavioral characteristics ubiqitious in ASD. In a relatively
      large sample of 256 children with ASD, ages 2-11, we examined the relationships
      between feeding and mealtime behaviors and social, communication, and cognitive
      levels as well repetitive and ritualistic behaviors, sensory behaviors, and
      externalizing and internalizing behaviors. Finally, we examined whether feeding
      habits were predictive of nutritional adequacy. In this sample, we found strong
      associations between parent reported feeding habits and (1) repetitive and
      ritualistic behaviors, (2) sensory features, and (3) externalizing and
      internalizing behavior. There was a lack of association between feeding behaviors
      and the social and communication deficits of ASD and cognitive levels. Increases
      in the degree of problematic feeding behaviors predicted decrements in
      nutritional adequacy. 

PMID- 24664636
TI  - UMBRELLA: Using MicroBes for the REgulation of heavy metaL mobiLity at ecosystem
      and landscape scAle.

PMID- 24664637
TI  - Atmospheric concentrations, gaseous-particulate distribution, and carcinogenic
      potential of polycyclic aromatic hydrocarbons in Assiut, Egypt.
AB  - The concentrations of 15 priority PAHs were determined in the atmospheric gaseous
      and particulate phases from nine sites across Assiut City, Egypt. While
      naphthalene, acenaphthene, and fluorene were the most abundant in the gaseous
      phase with average concentrations of 377, 184, and 181 ng/m(3),
      benzo[b]fluoranthene, chrysene, and benzo[g,h,i]perylene showed the highest
      levels in the particulate phase with average concentrations of 76, 6, and 52
      ng/m(3). The average total atmospheric concentration of target PAHs (1,590
      ng/m(3)) indicates that Assiut is one of the highest PAH-contaminated areas in
      the world. Statistical analysis revealed a significant difference between the
      levels of PAHs in the atmosphere of urban and suburban sites (P = 0.029 and 0.043
      for gaseous and particulate phases, respectively). Investigation of diagnostic
      PAH concentration ratios revealed vehicular combustion and traffic exhaust
      emissions as the major sources of PAHs with a higher contribution of gasoline
      rather than diesel vehicles in the sampled areas. Benzo[a]pyrene has the highest
      contribution (average = 32, 4% for gaseous and particulate phases) to the total
      carcinogenic activity (TCA) of atmospheric PAHs. While particulate phase PAHs
      have higher contribution to the TCA, gaseous phase PAHs present at higher
      concentrations in the atmosphere are more capable of undergoing atmospheric
      reactions to form more toxic derivatives.

PMID- 24664638
TI  - Degradation of tetracycline at a boron-doped diamond anode: influence of initial
      pH, applied current intensity and electrolyte.
AB  - The anodic oxidation of tetracycline was performed in an up-flow reactor,
      operating in batch mode with recirculation, using as anode a boron-doped diamond
      electrode. The influence on the degradation rate of solution initial pH (2 to
      12), applied current intensity (25 to 300 A m(-2)) and type of electrolyte
      (sodium sulphate or sodium chloride) were investigated. For the assays run at
      equal current density, with sodium sulphate as electrolyte, the solution's
      initial pH of 2 presented the highest absorbance and chemical oxygen demand
      removals. Regarding the influence of current density, for equal charge passed,
      the organic load removal rate decreased with the increase in applied current.
      When sodium sulphate was used as an electrolyte, high-performance liquid
      chromatography (HPLC) results have shown an almost complete removal of
      tetracycline after a 2-h assay. HPLC results have also shown the presence of
      oxamic acid as one of the intermediates of tetracycline anodic oxidation. The
      complete removal of tetracycline was much faster in the presence of chloride ions
      that promoted the complete degradation of this antibiotic in 30 min. However, in
      the presence of chloride ions, the tetracycline mineralization is slower, as
      observed by the lower organic carbon removal rate when compared to that of the
      tetracycline degradation in the presence of sulphate.

PMID- 24664639
TI  - Sinonasal mucosal melanoma: 20-year experience at a tertiary referral center.
AB  - BACKGROUND: Sinonasal melanoma (SNM) is a rare cancer with extremely poor
      prognosis. Detecting melanoma on frozen section has historically been considered
      to be unreliable. A review of cases of sinonasal melanoma treated at a tertiary
      referral center was conducted to analyze treatment outcomes and identify
      prognostic factors for survival. In addition, an investigation was performed
      correlating sinonasal melanoma on frozen section and permanent analysis. METHODS:
      An institutional review board-approved search of the pathology database for cases
      of primary sinonasal melanoma treated between 1991 and 2011 was performed.
      Fourteen cases were identified and the medical charts were reviewed. RESULTS:
      Eleven patients had tumors arising from the nasal cavity, 2 arose from the
      maxillary sinus, and 1 from the ethmoid sinuses. Mean duration of follow-up was
      20.7 (range, 1.4 to 84.5) months. Overall, 5-year recurrence-free survival and
      overall survival was 23% and 35%, respectively. All patients had surgical
      resection with intent for cure and all but 1 patient had adjuvant therapy.
      Survival analysis showed that positive margin status (log rank p = 0.031) and the
      presence of perineural/lymphovascular invasion (log rank p = 0.021) negatively
      affected recurrence-free survival and overall survival, respectively. Nine cases
      had evaluation of intraoperative frozen sections with 32 total sections submitted
      for analysis. When compared with final pathology, there was a 0% false negative
      rate. CONCLUSION: Based on this series, positive margins and the presence of
      perineural/lymphovascular invasion are negative predictors of survival. In
      addition, intraoperative frozen section analysis of sinonasal mucosal melanoma
      correlates well with final pathology.

PMID- 24664640
TI  - Analysis of two candidate genes for Basan syndrome.
AB  - Basan syndrome is an extremely rare ectodermal dysplasia with autosomal dominant
      inheritance and variable expressivity. The etiology of Basan syndrome remains
      unknown. To identify the Basan syndrome gene, we sequenced keratin 14 (KRT14) and
      SMARCAD1 in a previously unreported kindred with the disease. Sequencing of the
      coding regions and splice junctions of KRT14 and SMARCAD1 was performed using PCR
      amplified genomic DNA isolated from blood or saliva and standard PCR protocols.
      In vitro functional studies were performed for a variant identified in SMARCAD1.
      While direct sequencing of KRT14 failed to reveal any likely pathogenic sequence
      alterations or splice site variants, a heterozygous splicing variant (c.378+3A>T)
      that segregated with the disease was identified in the skin-specific isoform of
      SMARCAD1. In vitro studies failed to demonstrate a splicing defect in SMARCAD1.
      We screened two candidate genes for Basan syndrome in a 3-generation pedigree.
      The skin-specific isoform of SMARCAD1 remains a good candidate for this disease.

PMID- 24664641
TI  - Aging and oxidative stress reduce the response of human articular chondrocytes to
      insulin-like growth factor 1 and osteogenic protein 1.
AB  - OBJECTIVE: To determine the effects of aging and oxidative stress on the response
      of human articular chondrocytes to insulin-like growth factor 1 (IGF-1) and
      osteogenic protein 1 (OP-1). METHODS: Chondrocytes isolated from normal articular
      cartilage obtained from tissue donors were cultured in alginate beads or
      monolayer. Cells were stimulated with 50-100 ng/ml of IGF-1, OP-1, or both.
      Oxidative stress was induced using tert-butyl hydroperoxide. Sulfate
      incorporation was used to measure proteoglycan synthesis, and immunoblotting of
      cell lysates was performed to analyze cell signaling. Confocal microscopy was
      performed to measure nuclear translocation of Smad4. RESULTS: Chondrocytes
      isolated from the articular cartilage of tissue donors ranging in age from 24
      years to 81 years demonstrated an age-related decline in proteoglycan synthesis
      stimulated by IGF-1 and IGF-1 plus OP-1. Induction of oxidative stress inhibited
      both IGF-1- and OP-1-stimulated proteoglycan synthesis. Signaling studies showed
      that oxidative stress inhibited IGF-1-stimulated Akt phosphorylation while
      increasing phosphorylation of ERK, and that these effects were greater in cells
      from older donors. Oxidative stress also increased p38 phosphorylation, which
      resulted in phosphorylation of Smad1 at the Ser(206) inhibitory site and reduced
      nuclear accumulation of Smad1. Oxidative stress also modestly reduced OP-1
      stimulated nuclear translocation of Smad4. CONCLUSION: These results demonstrate
      an age-related reduction in the response of human chondrocytes to IGF-1 and OP-1,
      which are 2 important anabolic factors in cartilage, and suggest that oxidative
      stress may be a contributing factor by altering IGF-1 and OP-1 signaling.

PMID- 24664643
TI  - Transforming hair into heteroatom-doped carbon with high surface area.
AB  - Herein, a unique approach to dispose of human hair by pyrolizing it in a
      regulated environment is presented, yielding highly porous, conductive hair
      carbons with heteroatoms and high surface area. alpha-keratin in the protein
      network of hair serves as a precursor for the heteroatoms and carbon. The carbon
      framework is ingrained with heteroatoms such as nitrogen and sulfur, which
      otherwise are incorporated externally through energy-intensive, hazardous,
      chemical reactions using proper organic precursors. This judicious transformation
      of organic-rich waste not only addresses the disposal issue, but also generates
      valuable functional carbon materials from the discard. This unique synthesis
      strategy involving moderate activation and further graphitization enhances the
      electrical conductivity, while still maintaining the precious heteroatoms. The
      effect of temperature on the structural and functional properties is studied, and
      all the as-obtained carbons are applied as metal-free catalysts for the oxygen
      reduction reaction (ORR). Carbon graphitized at 900  degrees C emerges as a
      superior ORR electrocatalyst with excellent electrocatalytic performance, high
      selectivity, and long durability, demonstrating that hair carbon can be a
      promising alternative for costly Pt-based electrocatalysts in fuel cells. The ORR
      performance can be discussed in terms of heteroatom doping, surface properties,
      and electrical conductivity of the resulting porous hair carbon materials. 

PMID- 24664642
TI  - Reduction of arterial partial volume effects for improved absolute quantification
      of DSC-MRI perfusion estimates: comparison between tail scaling and prebolus
      administration.
AB  - PURPOSE: To evaluate and mutually compare the tail-scaling approach and the
      prebolus administration concept for reduction of arterial partial volume effects
      (PVEs), because reproducible absolute quantification of cerebral blood flow (CBF)
      by dynamic susceptibility contrast magnetic resonance imaging (MRI) is often
      hampered by PVEs in the arterial input function (AIF) registration. MATERIALS AND
      METHODS: Twenty healthy volunteers were scanned in a test-retest study with 7-20
      days between investigations to examine the quantitative values and the
      repeatability of CBF estimates obtained from the tail-scaling and the prebolus
      administration approaches. RESULTS: Average grey matter CBF was 80 +/- 18 mL/100
      g/min (mean +/- SD) using tail-scaling and 56 +/- 18 mL/100 g/min using prebolus
      administration. The intraclass correlation coefficient was 0.52 for the tail
      scaling approach and 0.86 for the prebolus administration concept. CONCLUSION:
      Both correction methods resulted in considerably reduced arterial PVEs, leading
      to quantitative estimates of perfusion approaching those typically obtained by
      other perfusion modalities. The CBF estimates obtained using the prebolus
      administration concept showed superior repeatability. Potential sources of
      uncertainty in the tail-scaling approach include the use of venous concentration
      curves influenced by PVEs or by geometric distortions (ie, vessel pixel shifts)
      in the steady-state period.

PMID- 24664645
TI  - Rapid pulsing artefacts in pulsed-field gradient double-quantum filtered COSY
      spectra.

PMID- 24664646
TI  - Canadian approval sought for controversial pain drug.

PMID- 24664647
TI  - Obsessive-compulsive disorder.

PMID- 24664644
TI  - Is there B cell involvement in a rat model of spontaneous idiopathic nephrotic
      syndrome treated with LF15-0195?
AB  - BACKGROUND: The Buffalo/Mna (Buff/Mna) rat spontaneously develops idiopathic
      nephrotic syndrome (INS), and its nephropathy recurs after the renal
      transplantation of a healthy graft. Only LF15-0195 is able to cause regression of
      the Buff/Mna nephropathy and to induce regulatory T cells, which decrease
      proteinuria when transferred into proteinuric Buff/Mna rats. Based on previous
      research on B cells in human INS, we evaluated the involvement of B cells in our
      model and the impact of LF15-0195. METHODS: We studied the effect of LF15-0195 on
      peripheral B cells by flow cytometry and quantitative reverse transcription
      polymerase chain reaction. B cells were purified from LF15-0195-treated Buff/Mna
      rats in remission, and transferred into proteinuric Buff/Mna rats. We treated the
      Buff/Mna rats with mitoxantrone and measured the depletion of B/T cells in
      parallel with proteinuria. RESULTS: LF15-0195 changed the phenotype of B cells:
      the number of naive mature B cells increased significantly, while the number of
      switched, transitional 1, and transitional 2 B cells decreased. There were no
      changes in the amount of memory, activated or regulatory B cells. We observed a
      significant increase of immunoglobulin (Ig)M mRNA transcripts in the LF15-0195
      treated Buff/Mna B cells compared to controls, but no difference in the level of
      IgG. This profile is consistent with a block in B cell maturation at the IgM to
      IgG switch. The transfer of B cells from LF15-0195-treated rats into proteinuric
      Buff/Mna rats did not have an effect on proteinuria. Mitoxantrone, despite
      causing a significant depletion of B cells, did not reduce proteinuria.
      CONCLUSION: Despite LF15-0195 acting on B cells, the beneficial effects of this
      drug on nephrotic syndrome did not involve the induction of regulatory B cells.
      Moreover, the B cell depletion was not effective in reducing proteinuria,
      indicating that B cells are not a therapeutic target.

PMID- 24664648
TI  - Compliance.

PMID- 24664649
TI  - Reduction of radial-head subluxation in children by triage nurses in the
      emergency department: a cluster-randomized controlled trial.
AB  - BACKGROUND: Radial-head subluxation is an easily identified and treated injury.
      We investigated whether triage nurses in the emergency department can safely
      reduce radial-head subluxation at rates that are not substantially lower than
      those of emergency department physicians. METHODS: We performed an open,
      noninferiority, cluster-randomized control trial. Children aged 6 years and
      younger who presented to the emergency department with a presentation consistent
      with radial-head subluxation and who had sustained a known injury in the previous
      12 hours were assigned to either nurse-initiated or physician-initiated
      treatment, depending on the day. The primary outcome was the proportion of
      children who had a successful reduction (return to normal arm usage). We used a
      noninferiority margin of 10%. RESULTS: In total, 268 children were eligible for
      inclusion and 245 were included in the final analysis. Of the children assigned
      to receive physician-initiated care, 96.7% (117/121) had a successful reduction
      performed by a physician. Of the children assigned to receive nurse-treatment
      care, 84.7% (105/124) had a successful reduction performed by a nurse. The
      difference in the proportion of successful radial head subluxations between the
      groups was 12.0% (95% confidence interval [CI] 4.8% to 19.7%). Noninferiority of
      nurse-initiated radial head subluxation was not shown. INTERPRETATION: In this
      trial, the rate of successful radial-head subluxation performed by nurses was
      inferior to the physician success rate. Although the success rate in the nurse
      initiated care group did not meet the non-inferiority margin, nurses were able to
      reduce radial head subluxation for almost 85% of children who presented with
      probable radial-head subluxation. TRIAL REGISTRATION: Clinical Trials.gov, no.
      NCT00993954.

PMID- 24664650
TI  - The increasing inefficiency of private health insurance in Canada.

PMID- 24664651
TI  - BC adds ethnic diversity to new public cord blood bank.

PMID- 24664652
TI  - South Africa ground zero for reforming drug patents.

PMID- 24664654
TI  - Electronic medical records: preparing for the inevitable crash.

PMID- 24664655
TI  - Rising antipsychotic prescriptions for children and youth: cross-sectoral
      solutions for a multimodal problem.

PMID- 24664656
TI  - Stopping cyberbullying requires a combined societal effort.

PMID- 24664657
TI  - Encapsulated cobalt-porphyrin as a catalyst for size-selective radical-type
      cyclopropanation reactions.
AB  - A cobalt-porphyrin catalyst encapsulated in a cubic M8 L6 cage allows
      cyclopropanation reactions in aqueous media. The caged-catalyst shows enhanced
      activities in acetone/water as compared to pure acetone. Interestingly, the M8 L6
      encapsulated catalyst reveals size-selectivity. Smaller substrates more easily
      penetrate through the pores of the "molecular ship-in-a-bottle catalysts" and are
      hence converted faster than bigger substrates. In addition, N-tosylhydrazone
      sodium salts are easy to handle reagents for cyclopropanation reactions under
      these conditions. 

PMID- 24664658
TI  - Impact of routine intraoperative cholangiography during laparoscopic
      cholecystectomy on bile duct injury.
AB  - BACKGROUND: The role of intraoperative cholangiography (IOC) in the diagnosis,
      prevention and management of bile duct injury (BDI) remains controversial. The
      aim of the present study was to determine the value of routine IOC in the
      diagnosis and management of BDI sustained during laparoscopic cholecystectomy
      (LC) at a high-volume centre. METHODS: A retrospective analysis of a single
      institution database was performed. Patients who underwent LC with routine IOC
      between October 1991 and May 2012 were included. RESULTS: Among 11,423
      consecutive LCs IOC was performed successfully in 95.7 per cent of patients. No
      patient had IOC-related complications. Twenty patients (0.17 per cent) sustained
      a BDI during LC, and the diagnosis was made during surgery in 18 patients. Most
      BDIs were type D according to the Strasberg classification. The sensitivity of
      IOC for the detection of BDI was 79 per cent; specificity was 100 per cent. All
      injuries diagnosed during surgery were repaired during the same surgical
      procedure. Two patients developed early biliary strictures that were treated by
      percutaneous dilatation and a Roux-en-Y hepaticojejunostomy with satisfactory
      long-term results. CONCLUSION: The routine use of IOC during LC in a high-volume
      teaching centre was associated with a low incidence of BDI, and facilitated
      detection and repair during the same surgical procedure with a good outcome.

PMID- 24664659
TI  - Fungicide resistance risk assessment based on traits associated with the rate of
      pathogen evolution.
AB  - BACKGROUND: A new fungicide resistance risk assessment method is described, based
      on traits (of pathogens, fungicides and agronomic systems) that are associated
      with rapid or slow occurrence of resistance. Candidate traits tested for their
      predictive value were those for which there was a mechanistic rationale that they
      could be determinants of the rate of resistance evolution. RESULTS: A dataset of
      61 European cases of resistance against single-site-acting fungicides was
      assembled. For each case, the number of years from product introduction to first
      detection of resistance (the FDR time) was quantified - varying from 2 to 24
      years. Short and long predicted FDR times represent high and low resistance risk
      respectively. Regression analysis identified traits that were statistically
      associated with FDR time. A model combining these traits explained 61% of the
      variation in FDR time. Validation showed that this predictive power was highly
      unlikely to have occurred by chance. CONCLUSION: Unlike previous methods, trait
      based risk assessment can be used to assess resistance risk for fungicides with
      new modes of action, when there is no prior knowledge of resistance behaviour.
      Risk predictions using the new method provide a more reliable basis for
      resistance management decisions. (c) 2014 Society of Chemical Industry.

PMID- 24664661
TI  - Involvement of adrenomedullin in spinal glial activation following chronic
      administration of morphine in rats.
AB  - BACKGROUND: Adrenomedullin (AM) belongs to the calcitonin gene-related peptide
      (CGRP) family. Our previous studies show that chronic exposure to morphine
      increases spinal AM bioactivity, contributing to the development and maintenance
      of morphine tolerance. This study investigated the possible involvement of AM in
      morphine-evoked gliosis. METHODS: Real-time polymerase chain reaction was
      performed to determine interleukin-1beta (IL-1beta), IL-6 and tumour necrosis
      factor-alpha (TNF-alpha) mRNAs in the spinal dorsal horn and cultured sensory
      ganglion explants. Immunohistochemistry was performed to identify spinal
      microglia and astrocytes. RESULTS: Repetitive intrathecal (i.t.) injection of
      morphine (20 MUg) increased the expression of IL-1beta, IL-6 and TNF-alpha mRNAs
      in the spinal dorsal horn. The co-administration of the selective AM receptor
      antagonist AM22-52 (36 MUg) markedly attenuated chronic morphine-evoked increase
      in IL-1beta and IL-6, but not TNF-alpha, mRNA levels. Exposure of cultured dorsal
      root ganglion (DRG) explants to morphine (3.3 MUmol/L) for 6 days up-regulated IL
      1beta and IL-6 mRNA expressions. The depletion of AM gene using small interfering
      RNA (siRNA) approach abolished morphine-evoked increase in IL-1beta and IL-6
      syntheses in the cultured DRG. The blockade of AM receptors by i.t. AM22-52 also
      inhibited chronic morphine-evoked cell hypertrophy of microglia and astrocytes as
      well as an increase in OX-42 and GFAP (glial fibrillary acidic protein)
      immunoreactivities. Furthermore, the 6-day treatment with AM (10 MUg, i.t.)
      induced morphological changes of microglia and astrocytes as well as an increase
      in IL-1beta, IL-6 and TNF-alpha mRNA levels in the spinal dorsal horn.
      CONCLUSION: The present study supports the idea that up-regulation of the
      pronociceptive mediator AM can recruit spinal glial cells, resulting in an
      increase in cytokines during chronic use of morphine.

PMID- 24664662
TI  - Streptomyces amritsarensis sp. nov., exhibiting broad-spectrum antimicrobial
      activity.
AB  - A new actinobacterium strain, designated 2A(T), was isolated from a soil sample
      collected from Guru Nanak Dev University, Punjab (India) and characterized using
      a polyphasic taxonomic approach. It showed antimicrobial activity against various
      Gram-positive and Gram-negative bacteria including drug resistant bacteria and
      fungi. The strain had chemotaxononomic and morphological properties typical of
      the genus Streptomyces. The 16S rRNA gene sequence of the strain showed 99.9,
      99.5 and 99.5 % similarity with Streptomyces flavotricini DSM 40152(T),
      Streptomyces toxytricini DSM 40178(T) and Streptomyces globosus DSM 40815(T),
      respectively. This strain formed a coherent cluster with them and shared DNA-DNA
      homology of 37.6 +/- 0.6, 34.4 +/- 0.5 and 33.1 +/- 0.4 % with type strains, S.
      flavotricini DSM 40152(T), S. globosus DSM 40815(T) and S. toxytricini DSM
      40178(T), respectively. Further, the strain was readily distinguished from the
      phylogenetic close relatives in a variety of morphological, physiological and
      biochemical properties. Based on the genotypic and phenotypic characteristics, it
      is proposed that strain 2A(T) represents a novel species in the genus
      Streptomyces, for which the name Streptomyces amritsarensis sp. nov. is proposed,
      with the type strain 2A(T) (=MTCC 11845(T)=JCM 19660(T)). 

PMID- 24664663
TI  - Pseudoruegeria limi sp. nov. isolated from mud flats in the Yellow Sea in Korea.
AB  - A Gram-negative, aerobic, non-motile and rod-shaped bacterial strain, D-17(T),
      was isolated from mud flats in the Yellow Sea in Korea. Phylogenetic trees based
      on the 16S rRNA gene sequence showed that strain D-17(T) belongs to the genus
      Pseudoruegeria and it shared 97.5 % similarity with the type strain of
      Pseudoruegeria haliotis WM67(T). The sequence similarities with Pseudoruegeria
      litimaris HD-43(T) and Pseudoruegeria aquimaris SW-255(T) were 96.9 and 96.1 %,
      respectively. Strain D-17(T) was found to grow with 0.5-6 % (w/v) NaCl, at 20-30 
      degrees C, and at pH 6.5-8.0. Strain D-17(T) was determined to contain Q-10 as
      the predominant ubiquinone and summed feature 8 (C18:1 omega7c and/or C18:1
      omega6c, as defined by the MIDI system) as the major fatty acids. The major polar
      lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, an
      unidentified aminolipid, an unidentified glycolipid, an unidentified lipid and
      four unidentified phospholipids. The DNA G+C content was determined to be 63.6
      mol%. The DNA-DNA relatedness with P. haliotis WM67(T) was 32.5 %. The
      differential phenotypic properties revealed that strain D-17(T) can be separated
      from other Pseudoruegeria species. Based on the data presented in this study,
      strain D-17(T) represents a novel species, for which the name Pseudoruegeria limi
      sp. nov. is proposed. The type strain is D-17(T) (=KCTC 32460(T) =JCM 19487(T)). 

PMID- 24664660
TI  - Genetic epilepsy syndromes without structural brain abnormalities: clinical
      features and experimental models.
AB  - Research in genetics of epilepsy represents an area of great interest both for
      clinical purposes and for understanding the basic mechanisms of epilepsy. Most
      mutations in epilepsies without structural brain abnormalities have been
      identified in ion channel genes, but an increasing number of genes involved in a
      diversity of functional and developmental processes are being recognized through
      whole exome or genome sequencing. Targeted molecular diagnosis is now available
      for different forms of epilepsy. The identification of epileptogenic mutations in
      patients before epilepsy onset and the possibility of developing therapeutic
      strategies tested in experimental models may facilitate experimental approaches
      that prevent epilepsy or decrease its severity. Functional analysis is essential
      for better understanding pathogenic mechanisms and gene interactions. In vitro
      experimental systems are either cells that usually do not express the protein of
      interest or neurons in primary cultures. In vivo/ex vivo systems are organisms or
      preparations obtained from them (e.g., brain slices), which should better model
      the complexity of brain circuits and actual pathophysiological conditions.
      Neurons differentiated from induced pluripotent stem cells generated from the
      skin fibroblasts of patients have recently allowed the study of mutations in
      human neurons having the genetic background of a given patient. However, there is
      remarkable complexity underlying epileptogenesis in the clinical dimension, as
      reflected by the fact that experimental models have not provided yet results
      having clinical translation and that, with a few exceptions concerning rare
      conditions, no new curative treatment has emerged from any genetic finding in
      epilepsy. 

PMID- 24664664
TI  - Bayesian inferences for beta semiparametric-mixed models to analyze longitudinal
      neuroimaging data.
AB  - Diffusion tensor imaging (DTI) is a quantitative magnetic resonance imaging
      technique that measures the three-dimensional diffusion of water molecules within
      tissue through the application of multiple diffusion gradients. This technique is
      rapidly increasing in popularity for studying white matter properties and
      structural connectivity in the living human brain. One of the major outcomes
      derived from the DTI process is known as fractional anisotropy, a continuous
      measure restricted on the interval (0,1). Motivated from a longitudinal DTI study
      of multiple sclerosis, we use a beta semiparametric-mixed regression model for
      the neuroimaging data. This work extends the generalized additive model
      methodology with beta distribution family and random effects. We describe two
      estimation methods with penalized splines, which are formalized under a Bayesian
      inferential perspective. The first one is carried out by Markov chain Monte Carlo
      (MCMC) simulations while the second one uses a relatively new technique called
      integrated nested Laplace approximation (INLA). Simulations and the neuroimaging
      data analysis show that the estimates obtained from both approaches are stable
      and similar, while the INLA method provides an efficient alternative to the
      computationally expensive MCMC method. 

PMID- 24664666
TI  - Pharmacogenetics of antiplatelet therapy.
AB  - There has been substantial progress toward understanding and investigating the
      specific genetic factors that influence interindividual variations in platelet
      directed therapy. There has also been substantial progress toward better
      understanding of the pharmacogenetics of drug metabolism and phamacodynamic
      response to platelet antagonists. We summarize the relationship between genetic
      polymorphisms, response to platelet antagonists, and clinical impact on patient
      treatment for the commonly used antiplatelet drugs. The challenge faced in
      translating genotype identification into improved clinical outcomes reflects the
      complexity involved in the genomic influence on drug metabolism and activation. 

PMID- 24664667
TI  - One-step synthesis of N-doped graphene quantum sheets from monolayer graphene by
      nitrogen plasma.
AB  - High-quality N-doped graphene quantum sheets are successfully fabricated from as
      grown monolayer graphene on Cu using nitrogen plasma, which can be transferred as
      a film-like layer or easily dispersed in an organic solvent for further
      optoelectronic or photoelectrochemical applications. 

PMID- 24664668
TI  - Peripheral facial palsy caused by neoplastic meningitis.
AB  - OBJECTIVES/HYPOTHESIS: To describe the clinical presentation of peripheral facial
      palsy caused by neoplastic meningitis. STUDY DESIGN: Retrospective case series.
      METHODS: Retrospective review, including accompanying symptoms and magnetic
      resonance imaging (MRI) findings. RESULTS: Between January and December 2011, six
      patients were diagnosed with peripheral facial palsy caused by neoplastic
      meningitis. The patient age at presentation ranged from 56 to 77 years. The tumor
      origins were as follows: malignant lymphoma (n = 3), lung cancer (n = 2), and
      kidney cancer (n = 1). In three patients, sudden sensorineural hearing loss
      accompanied the facial palsy. Three patients were judged to be tumor-free at the
      onset of the facial palsy. In two patients, the malignancy was not diagnosed at
      the onset of facial palsy and hearing loss. Only one patient was diagnosed as
      having a tumor at the onset of the facial palsy. On the MRI, a mass lesion was
      detected in the internal auditory canals (IAC) of four patients; one had a
      solitary IAC tumor. In this patient, the diagnosis required a histopathological
      study using a translabyrinthine approach. In the other two patients, the facial
      nerve was enhanced with gadolinium, but it was difficult to differentiate the
      observed condition from Bell's palsy. In these patients, repeated cytological
      studies led to the correct diagnoses. CONCLUSIONS: The clinical symptoms and MRI
      findings of peripheral facial palsy caused by neoplastic meningitis sometimes
      mimic those of benign facial palsy.

PMID- 24664669
TI  - Autism and anxiety in males with fragile X syndrome: an exploratory analysis of
      neurobehavioral profiles from a parent survey.
AB  - Although it is suspected that anxiety modifies the clinical presentation of
      autism in fragile X syndrome (FXS), neuropsychiatric co-morbidity profiles of
      these two disorders have not been extensively studied. The National Fragile X
      Survey was completed for 1,027 males with FXS, for whom yes/no information
      regarding the presence of several disorders is provided. Although the survey
      exhibited limited depth and lacked validation by standardized measures, this
      exploratory study was conducted to take advantage of the data as an opportunity
      for identifying future lines of inquiry. We addressed the following questions:
      (i) how do the co-morbidity profiles of FXS males with both autism and anxiety
      compare to those without anxiety?; (ii) do individuals with autism exhibit
      specific co-morbidity profiles compared to FXS males with anxiety only, or
      without either autism or anxiety?; (iii) how do co-morbidity profiles in children
      ages 3-11 differ from profiles of individuals >12 years? The group with autism
      and anxiety reported the highest prevalence of attention problems,
      hyperactivity/impulsivity, self-injurious behavior and aggressiveness. In
      addition, the lowest prevalence rates of these conditions were often observed in
      non-anxious groups regardless of autism status. Overall, this exploratory
      analysis generated several hypotheses for further study: (i) anxiety increases
      the severity of autism in FXS, particularly through additional behavioral
      abnormalities; (ii) some neuropsychiatric and behavioral conditions (i.e.,
      attention problems, hyperactivity/impulsivity, aggressiveness) are primarily
      related to comorbid anxiety, not autism; (iii) prevalence of behavioral
      abnormalities increases with age. Future studies evaluating these hypotheses
      should incorporate validated neurobehavioral assessments, and control for
      cognitive level.

PMID- 24664671
TI  - Using natural language processing and machine learning to identify gout flares
      from electronic clinical notes.
AB  - OBJECTIVE: Gout flares are not well documented by diagnosis codes, making it
      difficult to conduct accurate database studies. We implemented a computer-based
      method to automatically identify gout flares using natural language processing
      (NLP) and machine learning (ML) from electronic clinical notes. METHODS: Of
      16,519 patients, 1,264 and 1,192 clinical notes from 2 separate sets of 100
      patients were selected as the training and evaluation data sets, respectively,
      which were reviewed by rheumatologists. We created separate NLP searches to
      capture different aspects of gout flares. For each note, the NLP search outputs
      became the ML system inputs, which provided the final classification decisions.
      The note-level classifications were grouped into patient-level gout flares. Our
      NLP+ML results were validated using a gold standard data set and compared with
      the claims-based method used by prior literatures. RESULTS: For 16,519 patients
      with a diagnosis of gout and a prescription for a urate-lowering therapy, we
      identified 18,869 clinical notes as gout flare positive (sensitivity 82.1%,
      specificity 91.5%): 1,402 patients with >=3 flares (sensitivity 93.5%,
      specificity 84.6%), 5,954 with 1 or 2 flares, and 9,163 with no flare
      (sensitivity 98.5%, specificity 96.4%). Our method identified more flare cases
      (18,869 versus 7,861) and patients with >=3 flares (1,402 versus 516) when
      compared to the claims-based method. CONCLUSION: We developed a computer-based
      method (NLP and ML) to identify gout flares from the clinical notes. Our method
      was validated as an accurate tool for identifying gout flares with higher
      sensitivity and specificity compared to previous studies.

PMID- 24664670
TI  - Using fractional polynomials to model the effect of cumulative duration of
      exposure on outcomes: applications to cohort and nested case-control designs.
AB  - PURPOSE: Determining the nature of the relationship between cumulative duration
      of exposure to an agent and the hazard of an adverse outcome is an important
      issue in environmental and occupational epidemiology, public health and clinical
      medicine. The Cox proportional hazards regression model can incorporate time
      dependent covariates. An important class of continuous time-dependent covariates
      is that denoting cumulative duration of exposure. METHODS: We used fractional
      polynomial methods to describe the association between cumulative duration of
      exposure and adverse outcomes. We applied these methods in a cohort study to
      examine the relationship between cumulative duration of use of the antiarrhythmic
      drug amiodarone and the risk of thyroid dysfunction. We also used these methods
      with a conditional logistic regression model in a nested case-control study to
      examine the relationship between cumulative duration of use of bisphosphonate
      medication and the risk of atypical femur fracture. RESULTS: Using a cohort
      design and a Cox proportional hazards model, we found a non-linear relationship
      between cumulative duration of use of the antiarrhythmic drug amiodarone and the
      risk of thyroid dysfunction. The risk initially increased rapidly with increasing
      cumulative use. However, as cumulative duration of use increased, the rate of
      increase in risk attenuated and eventually levelled off. Using a nested case
      control design and a conditional logistic regression model, we found evidence of
      a linear relationship between duration of use of bisphosphonate medication and
      risk of atypical femur fractures. CONCLUSIONS: Fractional polynomials allow one
      to model the relationship between cumulative duration of medication use and
      adverse outcomes.

PMID- 24664672
TI  - Surface modification of titanium substrates with silver nanoparticles embedded
      sulfhydrylated chitosan/gelatin polyelectrolyte multilayer films for
      antibacterial application.
AB  - To develop Ti implants with potent antibacterial activity, a novel "sandwich
      type" structure of sulfhydrylated chitosan (Chi-SH)/gelatin (Gel) polyelectrolyte
      multilayer films embedding silver (Ag) nanoparticles was coated onto titanium
      substrate using a spin-assisted layer-by-layer assembly technique. Ag ions would
      be enriched in the polyelectrolyte multilayer films via the specific interactions
      between Ag ions and -HS groups in Chi-HS, thus leading to the formation of Ag
      nanoparticles in situ by photo-catalytic reaction (ultraviolet irradiation).
      Contact angle measurement and field emission scanning electron microscopy
      equipped with energy dispersive X-ray spectroscopy were employed to monitor the
      construction of Ag-containing multilayer on titanium surface, respectively. The
      functional multilayered films on titanium substrate [Ti/PEI/(Gel/Chi-SH/Ag) n
      /Gel] could efficiently inhibit the growth and activity of Bacillus subtitles and
      Escherichia coli onto titanium surface. Moreover, studies in vitro confirmed that
      Ti substrates coating with functional multilayer films remained the biological
      functions of osteoblasts, which was reflected by cell morphology, cell viability
      and ALP activity measurements. This study provides a simple, versatile and
      generalized methodology to design functional titanium implants with good cyto
      compatibility and antibacterial activity for potential clinical applications.

PMID- 24664673
TI  - Comparative performance of collagen nanofibers electrospun from different
      solvents and stabilized by different crosslinkers.
AB  - Collagen electrospun scaffolds well reproduce the structure of the extracellular
      matrix (ECM) of natural tissues by coupling high biomimetism of the biological
      material with the fibrous morphology of the protein. Structural properties of
      collagen electrospun fibers are still a debated subject and there are conflicting
      reports in the literature addressing the presence of ultrastructure of collagen
      in electrospun fibers. In this work collagen type I was successfully electrospun
      from two different solvents, trifluoroethanol (TFE) and dilute acetic acid
      (AcOH). Characterization of collagen fibers was performed by means of SEM, ATR
      IR, Circular Dichroism and WAXD. We demonstrated that collagen fibers contained a
      very low amount of triple helix with respect to pristine collagen (18 and 16% in
      fibers electrospun from AcOH and TFE, respectively) and that triple helix
      denaturation occurred during polymer dissolution. Collagen scaffolds were
      crosslinked by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), a
      commonly employed crosslinker for electrospun collagen, and 1,4-butanediol
      diglycidyl ether (BDDGE), that was tested for the first time in this work as
      crosslinking agent for collagen in the form of electrospun fibers. We
      demonstrated that BDDGE successfully crosslinked collagen and preserved at the
      same time the scaffold fibrous morphology, while scaffolds crosslinked with EDC
      completely lost their porous structure. Mesenchymal stem cell experiments
      demonstrated that collagen scaffolds crosslinked with BDDGE are biocompatible and
      support cell attachment.

PMID- 24664674
TI  - Cell type-specific epigenetic signatures accompany late stages of mouse retina
      development.
AB  - We have used ChIP-seq to map the distribution of two important histone H3
      modifications, H3K4me2 and H3K27me3, over the whole genome at multiple time
      points during late mouse retina development. We merged these data with our
      previous retina developmental expression profiles and show that there are several
      epigenetic signatures specific for different functional groups of genes. The main
      conclusion from our study is that epigenetic signatures defined by H3K4me2 and
      H3K27me3 can distinguish cell-type specific genes from widespread transcripts and
      may be reflective of cell specificity during retina maturation. Rod photoreceptor
      specific genes have a striking signature, a de novo accumulation of H3K4me2 and a
      complete absence of H3K27me3. We were able to use this signature in an unbiased
      search of the whole genome and identified essentially all the known rod
      photoreceptor genes as well as a group of novel genes that have a high
      probability of being rod photoreceptor specific. Comparison of our genome-wide
      chromatin signature maps with available data sets for Polymerase-II (Pol-II) and
      CRX binding sites and DNase1 Hypersensitive Sites (DHS) for retina shows great
      agreement. Because our approach is not dependent on high levels of gene
      expression, it provides a new way of identifying cell type-specific genes,
      particularly genes that may be involved in retinal diseases. 

PMID- 24664675
TI  - Programmed cell death during retinal development of the mouse eye.
AB  - Similar to other parts of the central nervous system, there are two types of
      programmed cell death during retinal development. In early development, the
      neuronal progenitor population is affected. In the mouse eye, this kind of
      programmed cell death begins at around embryonic day (E) 12.5 and peaks between
      E14.5 and E16.5. The second phase of programmed cell death occurs during
      synaptogenesis within the first 2 postnatal weeks. Important signaling mechanisms
      that induce programmed cell death of retinal progenitors appear to involve nerve
      growth factor acting on the proapoptotic receptor to p75 neurotrophin receptor
      (p75(NTR)) and transforming growth factor-beta. 

PMID- 24664676
TI  - Spatial and temporal localization of caveolin-1 protein in the developing retina.
AB  - Caveolin-1 (Cav-1), the signature protein of caveolae is expressed in several
      cell types in the adult retina and is linked to ocular pathologies including
      uveitis, diabetic retinopathy, and primary open angle glaucoma. Genetic ablation
      of Cav-1 causes retinal functional deficits due to disruptions in environmental
      homeostasis. To better understand Cav-1 function in the retina, we examined its
      expression/localization during postnatal retinal development. From P0-P5, Cav-1
      was detected only in the developing superficial retinal vessels, in hyaloid and
      choroidal vasculature, and in the retinal pigment epithelium (RPE). At P7,
      staining began to be observed centrally in radial cells in the neuroretina, and
      this staining increased dramatically by P9/10 in identifiable Muller glia.
      Prominent vascular staining continued throughout development. These results
      support the idea that Cav-1 is an indicator of Muller glial differentiation and
      suggests that it plays an important role in Muller cell function. 

PMID- 24664677
TI  - Glutathione S-transferase pi isoform (GSTP1) expression in murine retina
      increases with developmental maturity.
AB  - BACKGROUND AND AIMS: Glutathione S-transferase pi isoform (GSTP1) is an
      intracellular detoxification enzyme that catalyzes reduction of chemically
      reactive electrophiles and is a zeaxanthin-binding protein in the human macula.
      We have previously demonstrated that GSTP1 levels are decreased in human age
      related macular degeneration (AMD) retina compared to normal controls (Joshi et
      al., Invest Ophthalmol Vis Sci, e-abstract, 2009). We also showed that GSTP1
      levels parallel survival of human retinal pigment epithelial (RPE) cells exposed
      to ultraviolet (UV) light, and GSTP1 over-expression protects them against UV
      light damage (Joshi et al., Invest Ophthalmol Vis Sci, e-abstract, 2010). In the
      present work, we determined the developmental time course of GSTP1 expression in
      murine retina and in response to light challenge. METHODS: Eyes from BALB/c mice
      at postnatal day 20, 1 month, and 2 months of age were prepared for retinal
      protein extraction and cryo sectioning, and GSTP1 levels in the retina were
      analyzed by Western blot and immunohistochemistry (IHC). Another group of BALB/c
      mice with the same age ranges was exposed to 1000 lx of white fluorescent light
      for 24 h, and their retinas were analyzed for GSTP1 expression by Western blot
      and IHC in a similar manner. RESULTS: GSTP1 levels in the murine retina increased
      in ascending order from postnatal day 20, 1 month, and 2 months of age. Moreover,
      GSTP1 expression in murine retina at postnatal day 20, 1 month, and 2 months of
      age increased in response to brief light exposure compared to age-matched
      controls under normal condition. CONCLUSIONS: GSTP1 expression in retina
      increases with developmental age in mice and accompanies murine retinal
      maturation. Brief exposure to light induces GSTP1 expression in the murine retina
      across various developmental ages. GSTP1 induction may be a protective response
      to light-induced oxidative damage in the murine retina.

PMID- 24664678
TI  - RETINA-specific expression of Kcnv2 is controlled by cone-rod homeobox (Crx) and
      neural retina leucine zipper (Nrl).
AB  - Cone dystrophy with supernormal rod response (CDSRR) is an autosomal recessive
      disorder that leads to progressive retinal degeneration with a distinct
      electroretinogram (ERG) phenotype. CDSRR patients show reduced sensitivity to dim
      light, augmented response to suprathreshold light and reduced response to
      flicker. The disorder is caused by mutations in the KCNV2 gene, which encodes the
      Kv11.1 subunit of a voltage-gated potassium channel. Here, we studied the retina
      specific expression and cis-regulatory activity of the murine Kcnv2 gene using
      electroporation of explanted retinas. Using qRT-PCR profiling of early postnatal
      retinas, we showed that Kcnv2 expression increased towards P14, which marks the
      beginning of visual activity in mice. In vivo electroporation of GFP-Kcnv2
      expressing plasmids revealed that Kv11.1 localizes to the inner segment membranes
      of adult P21 photoreceptors. Using bioinformatic prediction and chromatin
      immunoprecipitation (ChIP), we identified two Crx binding sites (CBS) and one Nrl
      binding site (NBS) in the Kcnv2 promoter. Reporter electroporation of the wild
      type promoter region induced strong DsRed expression, indicating high regulatory
      activity, whereas shRNA-mediated knockdown of Crx and Nrl resulted in reduced
      Kcnv2 promoter activity and low endogenous Kcnv2 mRNA expression in the retina.
      Site-directed mutagenesis of the CBS and NBS demonstrated that CBS2 is crucial
      for Kcnv2 promoter activity. We conclude that nucleotide changes in evolutionary
      conserved CBS could impact retina-specific expression levels of Kcnv2. 

PMID- 24664679
TI  - AIPL1 protein and its indispensable role in cone photoreceptor function and
      survival.
AB  - Mutations in Aryl hydrocarbon receptor interacting protein like-1 (AIPL1) are
      linked to Leber congenital amaurosis (LCA), a severe blinding disease that occurs
      in early childhood. The severity of disease is due to requirement for AIPL1 in
      both rod and cone photoreceptor cell survival and function. Aipl1 is expressed
      very early during retinal development in both rods and cones. In adult primates,
      robust expression of Aipl1 is found in rods but not in cones. Mouse models
      revealed the importance of AIPL1 in stability and function of heteromeric
      phosphodiesterase 6 (PDE6), an enzyme needed for visual response. However, the
      need for AIPL1 in cone cell survival and function is not clearly understood. In
      this chapter, using results obtained from multiple lines of animal models, we
      discuss the role for AIPL1 in photoreceptors. 

PMID- 24664680
TI  - Primate short-wavelength cones share molecular markers with rods.
AB  - Macaca, Callithrix jacchus marmoset monkey, Pan troglodytes chimpanzee and human
      retinas were examined to define if short wavelength (S) cones share molecular
      markers with L&M cone or rod photoreceptors. S cones showed consistent
      differences in their immunohistochemical staining and expression levels compared
      to L&M cones for "rod" Arrestin1 (S-Antigen), "cone" Arrestin4, cone alpha
      transducin, and Calbindin. Our data verify a similar pattern of expression in
      these primate retinas and provide clues to the structural divergence of rods and
      S cones versus L&M cones, suggesting S cone retinal function is "intermediate"
      between them. 

PMID- 24664681
TI  - Exploration of cone cyclic nucleotide-gated channel-interacting proteins using
      affinity purification and mass spectrometry.
AB  - Photopic (cone) vision essential for color sensation, central vision, and visual
      acuity is mediated by the activation of photoreceptor cyclic nucleotide-gated
      (CNG) channels. Naturally occurring mutations in the cone channel subunits CNGA3
      and CNGB3 are associated with achromatopsia and cone dystrophies. This work
      investigated the functional modulation of cone CNG channel by exploring the
      channel-interacting proteins. Retinal protein extracts prepared from cone
      dominant Nrl (- / -) mice were used in CNGA3 antibody affinity purification,
      followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)
      separation and matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry analysis. The peptide mass fingerprinting of the tryptic
      digests and database search identified a number of proteins including spectrin
      alpha-2, ATPase (Na(+)/K(+) transporting) alpha-3, alpha and beta subunits of ATP
      synthase (H(+) transporting, mitochondrial F1 complex), and alpha-2 subunit of
      the guanine nucleotide-binding protein. In addition, the affinity-binding assays
      demonstrated an interaction between cone CNG channel and calmodulin but not cone
      Na(+)/Ca(2+)-K(+) exchanger in the mouse retina. Results of this study provide
      insight into our understanding of cone CNG channel-interacting proteins and the
      functional modulations. 

PMID- 24664682
TI  - Electrophysiological characterization of rod and cone responses in the baboon
      nonhuman primate model.
AB  - Many monogenic retinal diseases target the human macula, and evaluating genetic
      treatments for these diseases in rodent models which lack a macula can be
      limiting. To better test the likelihood that novel treatments will be relevant to
      patients, assessing expression and distribution may be undertaken in a nonhuman
      primate (NHP) model. The purpose of this study was to establish baseline
      functional characteristics in the baboon (Papio anubis) eye to establish a
      control dataset for future experiments testing novel genetic therapies.
      Electroretinography (ERG) was conducted on 12 young (~ 3 years of age) dark
      adapted baboons. Scotopic responses were measured in response to a series of
      light intensities followed by a 10-min period of light adaptation after which
      photopic responses were measured following the same series of light intensities.
      At the highest flash intensity, scotopic amplitudes were 334 +/- 10 uV and 458 +/
      15 uV for a- and b-waves, respectively. At the highest flash intensity, photopic
      amplitudes were 82 +/- 5 uV and 81 +/- 4 uV for a- and b-waves, respectively.
      Waveforms for scotopic responses were similar in shape to rodent scotopic
      responses. In contrast, photopic baboon waveforms were quite different in shape
      from those of rodents and were more similar to waveforms recorded from humans or
      other NHPs. These results are consistent with the differences in the photopic
      visual system in rodents versus primates (presence of a macula) and provide an
      excellent baseline for future studies testing novel therapies in the baboon
      model.

PMID- 24664683
TI  - Animal Models, in "The Quest to Decipher RPE Phagocytosis".
AB  - Renewal and elimination of aged photoreceptor outer segment (POS) tips by cells
      from the retinal pigment epithelial (RPE) is a daily rhythmic process that is
      crucial for long-term vision. Anomalies can arise during any of the sequential
      steps required for completion of this phagocytic function, from POS recognition
      to complete digestion of POS components. During the past 15 years, many animal
      models helped us characterize the molecular machinery implicated in RPE
      phagocytosis as well as understand associated defects leading to various retinal
      pathologies. Depending on which part of the machinery is flawed, phenotypes can
      either appear early in life, such as retinitis pigmentosa or Usher syndrome, or
      develop with aging of the individual, like age-related macular degeneration,
      affecting first either the peripheral or the central retina. This chapter
      describes mouse and rat models related to defective phagocytosis, and how they
      have been a tremendous help for us to comprehend RPE phagocytosis, its rhythm,
      and its failures. 

PMID- 24664684
TI  - In vivo and in vitro monitoring of phagosome maturation in retinal pigment
      epithelium cells.
AB  - The ingestion and degradation of photoreceptor disk membranes is a critical and
      major role for the retinal pigment epithelium (RPE). To help elucidate the
      cellular events involved in this role, functional in vivo and in vitro assays
      need to be developed further. Here we propose a method to help monitor phagosome
      maturation, using antibodies against different epitopes of opsin. We show that
      antibodies specific for the C-terminus of opsin label only immature phagosomes
      located in the apical region of the RPE. In contrast, antibodies recognizing the
      N-terminus also label more mature phagosomes, located more basally. The combined
      use of antibodies against different opsin epitopes thus provides a valuable tool
      in the study of phagosome maturation in the RPE. 

PMID- 24664685
TI  - Lack of effect of microfilament or microtubule cytoskeleton-disrupting agents on
      restriction of externalized phosphatidylserine to rod photoreceptor outer segment
      tips.
AB  - In the mammalian retina, life-long renewal of rod photoreceptor outer segments
      involves circadian shedding of distal outer segment tips and their prompt
      phagocytosis by the adjacent retinal pigment epithelium (RPE) every morning after
      light onset. Failure of this process causes retinal dystrophy in animal models
      and its decline likely contributes to retinal aging and some forms of
      degeneration of the human retina. We previously found that surface exposure of
      the membrane phospholipid phosphatidylserine (PS) is restricted to outer segment
      tips with discrete boundaries in mouse retina and that both frequency and length
      of tips exposing PS peak after light onset. Here, we sought to test mechanisms
      photoreceptors use to restrict PS specifically to their outer segment tips. To
      this end, we tested whether nocodazole or cytochalasin D, perturbing microtubule
      or F-actin microfilament cytoskeleton, respectively, affect localization of
      externalized PS at outer segment tips. Fluorescence imaging of PS exposed by rods
      in freshly dissected, live mouse retina showed normal PS demarcation of outer
      segment tips regardless of drug treatment. These results suggest that the
      mechanism that restricts externalized PS to rod tips is independent of F-actin
      and microtubule cytoskeletal systems. 

PMID- 24664686
TI  - Vacuolar ATPases and their role in vision.
AB  - Vacuolar ATPases (v-ATPases) hydrolyze adenosine triphospate (ATP) to pump
      protons across cell membranes. Mutations in v-ATPase subunits are implicated in
      three human disorders: distal renal tubular acidosis, osteopetrosis, and cutis
      laxa type II. In the eye, the role of v-ATPases is only emerging. Mutations in v
      ATPase subunits are not linked to human blindness, but altered proton pump
      function may underlie ocular pathologies. For example, inhibition of v-ATPase by
      A2E may accentuate age-related macular degeneration (AMD). In animal models, v
      ATPase mutations perturb the retinal pigment epithelium (RPE) and photoreceptor
      outer segment (OS) phagocytosis, an event linked to retinal degeneration. As the
      RPE plays essential roles in eye development and vision, the study of v-ATPase
      induced RPE dysfunction may improve our understanding of RPE diseases. 

PMID- 24664687
TI  - Rescue of compromised lysosomes enhances degradation of photoreceptor outer
      segments and reduces lipofuscin-like autofluorescence in retinal pigmented
      epithelial cells.
AB  - Healthful cell maintenance requires the efficient degradative processing and
      removal of waste material. Retinal pigmented epithelial (RPE) cells have the
      onerous task of degrading both internal cellular debris generated through
      autophagy as well as phagocytosed photoreceptor outer segments. We propose that
      the inadequate processing material with the resulting accumulation of cellular
      waste contributes to the downstream pathologies characterized as age-related
      macular degeneration (AMD). The lysosomal enzymes responsible for clearance
      function optimally over a narrow range of acidic pH values; elevation of
      lysosomal pH by compounds like chloroquine or A2E can impair degradative enzyme
      activity and lead to a lipofuscin-like autofluorescence. Restoring acidity to the
      lysosomes of RPE cells can enhance activity of multiple degradative enzymes and
      is therefore a logical target in early AMD. We have identified several approaches
      to reacidify lysosomes of compromised RPE cells; stimulation of beta-adrenergic,
      A2A adenosine and D5 dopamine receptors each lowers lysosomal pH and improves
      degradation of outer segments. Activation of the CFTR chloride channel also
      reacidifies lysosomes and increases degradation. These approaches also restore
      the lysosomal pH of RPE cells from aged ABCA4(-/-) mice with chronically high
      levels of A2E, suggesting that functional signaling pathways to reacidify
      lysosomes are retained in aged cells like those in patients with AMD. Acidic
      nanoparticles transported to RPE lysosomes also lower pH and improve degradation
      of outer segments. In summary, the ability of diverse approaches to lower
      lysosomal pH and enhance outer segment degradation support the proposal that
      lysosomal acidification can prevent the accumulation of lipofuscin-like material
      in RPE cells. 

PMID- 24664688
TI  - The role of bestrophin-1 in intracellular Ca(2+) signaling.
AB  - Mutations in the BEST1 gene lead to a variety of retinal degenerations, among
      them Best's vitelliforme macular degeneration. To clarify the mechanism of the
      disease, the understanding of the function of BEST1 gene product, bestrophin-1,
      is mandatory. In overexpression studies bestrophin-1 appeared to function as a
      Ca(2+)-dependent Cl channel. On the other hand, bestrophin-1 is able to
      participate in intracellular Ca(2+) signaling. Endogenously expressed bestrophin
      1 largely localized to the cytosolic compartment close to the basolateral
      membrane of the retinal pigment epithelium (RPE) as it can be shown using
      differential centrifugation, immunohistochemistry, and transmission electron
      microscopy. To elucidate a cytosolic function of bestrophin-1, we explored the
      store-operated Ca(2+) entry in short-time cultured porcine RPE cells. Depletion
      of cytosolic Ca(2+)stores by SERCA inhibition led to activation of Orai-1 Ca(2+)
      channels. This resulted in an influx of extracellular Ca(2+) into the cell which
      was reduced when bestrophin-1 expression was knocked down using siRNA techniques.
      Quantification of Ca(2+) which can be released from cytosolic Ca(2+) stores
      revealed that after reduction of bestrophin-1 expression less Ca(2+) is stored in
      ER Ca(2+) stores. Thus, bestrophin-1 functions as an intracellular Cl channel
      which helps to accumulate and to release Ca(2+) from stores by conducting the
      counterion for Ca(2+). 

PMID- 24664689
TI  - Application of next-generation sequencing to identify genes and mutations causing
      autosomal dominant retinitis pigmentosa (adRP).
AB  - The goal of our research is to identify genes and mutations causing autosomal
      dominant retinitis pigmentosa (adRP). For this purpose we established a cohort of
      more than 250 independently ascertained families with adRP in the Houston
      Laboratory for Molecular Diagnosis of Inherited Eye Diseases. Affected members of
      each family were screened for disease-causing mutations in genes and gene regions
      that are commonly associated with adRP. By this approach, we detected mutations
      in 65 % of the families, leaving 85 families that are likely to harbor mutations
      outside of the "common" regions or in novel genes. Of these, 32 families were
      tested by several types of next-generation sequencing (NGS), including (a)
      targeted polymerase chain reaction (PCR) NGS, (b) whole exome NGS, and (c)
      targeted retinal-capture NGS. We detected mutations in 11 of these families (31
      %) bringing the total detected in the adRP cohort to 70 %. Several large families
      have also been tested for linkage using Afymetrix single nucleotide polymorphism
      (SNP) arrays. 

PMID- 24664690
TI  - Digital quantification of Goldmann visual fields (GVFs) as a means for genotype
      phenotype comparisons and detection of progression in retinal degenerations.
AB  - PURPOSE: To develop a reliable and efficient digital method to quantify
      planimetric Goldmann visual field (GVF) data to monitor disease course and
      treatment responses in retinal degenerative diseases. METHODS: A novel method to
      digitally quantify GVFs using Adobe Photoshop CS3 was developed for comparison to
      traditional digital planimetry (Placom 45C digital planimeter; Engineer Supply,
      Lynchburg, Virginia, USA). GVFs from 20 eyes from 10 patients with Stargardt
      disease were quantified to assess the difference between the two methods (a total
      of 230 measurements per method). This quantification approach was also applied to
      13 patients with X-linked retinitis pigmentosa (XLRP) with mutations in RPGR.
      RESULTS: Overall, measurements using Adobe Photoshop were more rapidly performed
      than those using conventional planimetry. Photoshop measurements also exhibited
      less inter- and intraobserver variability. GVF areas for the I4e isopter in
      patients with the same mutation in RPGR who were nearby in age had similar
      qualitative and quantitative areas. CONCLUSIONS: Quantification of GVFs using
      Adobe Photoshop is quicker, more reliable, and less user dependent than
      conventional digital planimetry. It will be a useful tool for both retrospective
      and prospective studies of disease course as well as for monitoring treatment
      response in clinical trials for retinal degenerative diseases.

PMID- 24664691
TI  - Simplified system to investigate alteration of retinal neurons in diabetes.
AB  - Diabetic retinopathy (DR) is traditionally considered as a microvascular
      complication in diabetic retinas. Emerging evidences suggest that the alteration
      of neuronal function and the death of retinal neurons are part of DR pathology.
      However, surprisingly little is known about how retinal neurons behave in DR. As
      diabetic animals are chronicle models that are difficult and expensive to
      maintain, we used a chemical hypoxia model that mimics the later stage of
      diabetes and investigated its potential in predicting retinal cell behaviors in
      diabetes in an efficient manner. In this chapter, we discuss the similarities and
      differences between diabetic and hypoxic models and the usefulness and limitation
      of the cobalt-chloride-generated hypoxia system in mice for studying retinal
      neurobiology in diabetes. 

PMID- 24664692
TI  - What is the nature of the RGC-5 cell line?
AB  - The immortalized RGC-5 cell line has been widely used as a cell culture model to
      study the neurobiology of retinal ganglion cells (RGCs). The cells were
      originally introduced as derived from rat RGC showing expression of various
      neuronal markers, in particular the RGC-characteristic proteins Brn3 and Thy1.
      Recent data gave rise to concerns regarding the origin and nature of the cells.
      RGC-5 cells were identified to be of mouse origin and their expression of RGC
      characteristics was questioned by some laboratories. This article summarizes the
      available data on the properties of RGC-5, discusses common protocols for their
      differentiation and is aimed at providing researchers some guidelines on the
      benefits and limitations of RGC-5 for research. 

PMID- 24664693
TI  - Modeling retinal dystrophies using patient-derived induced pluripotent stem
      cells.
AB  - Retinal degenerative disease involving photoreceptor (PR) cell loss results in
      permanent vision loss and often blindness. Generation of induced pluripotent stem
      cell (iPSC)-derived retinal cells and tissues from individuals with retinal
      dystrophies is a relatively new and promising method for studying retinal
      degeneration mechanisms in vitro. Recent advancements in strategies to
      differentiate human iPSCs (hiPSCs) into 3D retinal eyecups with a strong
      resemblance to the mature retina raise the possibility that this system could
      offer a reliable model for translational drug studies. However, despite the
      potential benefits, there are challenges that remain to be overcome before stem
      cell-derived retinal eyecups can be routinely used to model human retinal
      diseases. This chapter will discuss both the potential of these 3D eyecup
      approaches and the nature of some of the challenges that remain. 

PMID- 24664694
TI  - Mutation K42E in dehydrodolichol diphosphate synthase (DHDDS) causes recessive
      retinitis pigmentosa.
AB  - A single-nucleotide mutation in the gene that encodes DHDDS has been identified
      by whole exome sequencing as the cause of the non-syndromic recessive retinitis
      pigmentosa (RP) in a family of Ashkenazi Jewish origin in which three of the four
      siblings have early onset retinal degeneration. The peripheral retinal
      degeneration in the affected siblings was evident in the initial examination in
      1992 and only one had detectable electroretinogram (ERG) that suggested cone-rod
      dysfunction. The pigmentary retinal degeneration subsequently progressed rapidly.
      The identified mutation changes the highly conserved residue Lys42 to Glu,
      resulting in lower catalytic efficiency. Patterns of plasma transferrin
      isoelectric focusing gel were normal in all family members, indicating no
      significant abnormality in protein glycosylation. Dolichols have been shown to
      influence the fluidity and of the membrane and promote vesicle fusion.
      Considering that photoreceptor outer segments contain stacks of membrane discs,
      we believe that the mutation may lead to low dolichol levels in photoreceptor
      outer segments, resulting in unstable membrane structure that leads to
      photoreceptor degeneration. 

PMID- 24664695
TI  - IROme, a new high-throughput molecular tool for the diagnosis of inherited
      retinal dystrophies-a price comparison with Sanger sequencing.
AB  - The molecular diagnosis of retinal dystrophies (RD) is difficult because of
      genetic and clinical heterogeneity. Previously, the molecular screening of genes
      was done one by one, sometimes in a scheme based on the frequency of sequence
      variants and the number of exons/length of the candidate genes. Payment for these
      procedures was complicated and the sequential billing of several genes created
      endless paperwork. We therefore evaluated the costs of generating and sequencing
      a hybridization-based DNA library enriched for the 64 most frequently mutated
      genes in RD, called IROme, and compared them to the costs of amplifying and
      sequencing these genes by the Sanger method. The production cost generated by the
      high-throughput (HT) sequencing of IROme was established at CHF 2,875.75 per
      case. Sanger sequencing of the same exons cost CHF 69,399.02. Turnaround time of
      the analysis was 3 days for IROme. For Sanger sequencing, it could only be
      estimated, as we never sequenced all 64 genes in one single patient. Sale cost
      for IROme calculated on the basis of the sale cost of one exon by Sanger
      sequencing is CHF 8,445.88, which corresponds to the sale price of 40 exons. In
      conclusion, IROme is cheaper and faster than Sanger sequencing and therefore
      represents a sound approach for the diagnosis of RD, both scientifically and
      economically. As a drop in the costs of HT sequencing is anticipated, target
      resequencing might become the new gold standard in the molecular diagnosis of RD.

PMID- 24664696
TI  - Genetic heterogeneity and clinical outcome in a Swedish family with retinal
      degeneration caused by mutations in CRB1 and ABCA4 genes.
AB  - Genetic mechanisms underlying severe retinal dystrophy in a large Swedish family
      presenting two distinct phenotypes, Leber congenital amaurosis and Stargardt
      disease were investigated. In the family, four patients with Leber congenital
      amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1
      gene, while of two cases with Stargardt disease, one was homozygous for c.5461
      10T>C in the ABCA4 gene and another was a compound heterozygous for c.5461-10T>C
      and a novel ABCA4 mutation c.4773+3 A>G. Sequence analysis of the entire ABCA4
      gene in patients with Stargardt disease revealed complex alleles with additional
      sequence variants.Our results provide evidence of genetic complexity causative of
      different clinical features present in the same family, which is an obvious
      challenge for ophthalmologists, molecular geneticists and genetic counsellors. 

PMID- 24664697
TI  - FAM161A, a novel centrosomal-ciliary protein implicated in autosomal recessive
      retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is an inherited disease of the retina leading to vision
      impairment due to progressive photoreceptor cell death. Homozygous and compound
      heterozygous null mutations in the CRX-regulated FAM161A gene of unknown function
      were identified as a cause for autosomal recessive RP (RP28) in patients from
      India, Germany, Israel, the Palestinian territories, and the USA. The FAM161A
      protein has been found to be localized to the connecting cilium, the basal body,
      and the adjacent centriole in mammalian photoreceptors and was also present in
      synaptic layers and ganglion cells of the retina. In addition, FAM161A was shown
      to be part of microtubule-organizing centers in cultured cells and associates
      with the intracellular microtubule network. Moreover, FAM161A directly binds to
      microtubules and increases the acetylation of alpha-tubulin. An evolutionary
      highly conserved, C-terminal protein domain (UPF0564) of FAM161A was shown to
      mediate microtubule association, homo- and heterotypic interaction among UPF0564
      containing proteins and binding to several ciliopathy-associated proteins. In
      summary, FAM161A is a novel centrosomal-ciliary protein that likely is implicated
      in the regulation of microtubule-based cellular processes in the retina. 

PMID- 24664698
TI  - Molecular pathology of macrophages and interleukin-17 in age-related macular
      degeneration.
AB  - The pathology of age-related macular degeneration (AMD) is characterized by
      degeneration of photoreceptors and retinal pigment epithelial cells as well as by
      changes of choroidal capillaries in the macula. Although AMD is not a typical
      uveitis, there is a consistence and an imbalance of ocular para-inflammation.
      Ocular inflammation, particularly in the macula, plays a critical role in AMD
      pathogenesis. The inflammatory and immune-related elements involved in AMD
      include inflammatory and related cells as well as the secreted molecules and
      factors from these cells. Innate immune system elements such as macrophages and
      cytokines play an important role in AMD pathology and pathogenesis. This chapter
      reviews the observed deviation in macrophage plasticity and the elevated
      expression of interleukin-17 in AMD eyes while discussing potential contributions
      to AMD pathogenesis. Targeting of these specific inflammatory pathways and
      molecules at appropriate times should be explored and may become promising novel
      adjunct agents to AMD therapy. 

PMID- 24664699
TI  - The role of monocytes and macrophages in age-related macular degeneration.
AB  - White blood cells, particularly monocytes and their descendants, macrophages,
      have been implicated in age-related macular degeneration (AMD) pathology. In this
      minireview, we describe the current knowledge of monocyte and macrophage
      involvement in AMD. Chemokine receptors present on these cells such as CCR1,
      CCR2, and CX3CR1, and their roles in monocyte/macrophage recruitment to sites of
      injury and inflammation in the context of AMD will be reviewed. Mice models for
      perturbation of chemokine receptors that recapitulate some of the features of AMD
      are also described. The body of evidence from human and rodent studies at this
      point in time suggests that monocyte and macrophages may modulate the course of
      AMD. 

PMID- 24664700
TI  - Microglia in the aging retina.
AB  - In the healthy retina, microglial cells represent a self-renewing population of
      innate immune cells, which constantly survey their microenvironment. Equipped
      with receptors, a microglial cell detects subtle cellular damage and rapidly
      responds with activation, migration, and increased phagocytic activity. While the
      involvement of microglial cells has been well characterized in monogenic retinal
      disorders, it is still unclear how they contribute to the onset of retinal aging
      disorders including age-related macular degeneration (AMD). There is evidence,
      that microglial activation is not solely a secondary manifestation of retinal
      tissue damage in age-related disorders. Thus, work in the aging rodent and human
      retina suggests that long-lived and genetically predisposed microglia transform
      into a dystrophic state, with loss of neuroprotective functions. In this concept,
      malfunction of aging microglia can trigger a chronic low-grade inflammatory
      environment that favors the onset and progression of retinal degeneration. 

PMID- 24664701
TI  - The role of complement dysregulation in AMD mouse models.
AB  - Variations in several complement genes are now known to be significant risk
      factors for the development of age-related macular degeneration (AMD). Despite
      dramatic effects on disease susceptibility, the underlying mechanisms by which
      common polymorphisms in complement proteins alter disease risk have remained
      unclear. Genetically modified mice in which the activity of the complement has
      been altered are available and can be used to investigate the role of complement
      in the pathogenesis of AMD. In this mini review, we will discuss some existing
      complement models of AMD and our efforts to develop and characterize the ocular
      phenotype in a variety of mice in which complement is either chronically
      activated or inhibited. A spectrum of complement dysregulation was modeled on the
      APOE4 AMD mouse model by crossing these mice to complement factor H knockout (cfh
      /-) mice to test the impact of excess complement activation, and by crossing them
      to soluble-complement-receptor-1-related protein y (sCrry) mice, in which sCrry
      acts as a potent inhibitor of mouse complement acting in a manner similar to CFH.
      In addition, we have also generated humanized CFH mice expressing normal and risk
      variants of CFH. 

PMID- 24664702
TI  - Prolonged SRC kinase activation, a mechanism to turn transient, sublytic
      complement activation into a sustained pathological condition in retinal pigment
      epithelium cells.
AB  - Age-related macular degeneration (AMD) is a slowly progressing multifactorial
      disease involving genetic abnormalities and environmental insults. Genetic
      studies have demonstrated that polymorphisms in different complement proteins
      increase the risk for developing AMD. Previously, we have shown that in retinal
      pigment epithelium (RPE) monolayers, exposure to oxidative stress reduced
      complement inhibition on the cell surface, with the resulting increase in
      complement activation leading to vascular endothelial growth factor (VEGF)
      release and VEGF-receptor-2-mediated disruption of the monolayer barrier
      function. Complement activation was found to be sublytic and transient and
      require the assembly of the membrane attack complex (MAC). Here, we asked how
      this transient, sublytic complement activation could trigger long-term
      pathological changes in RPE cells. The initial activation of the L-type voltage
      gated calcium channels was followed by calcium influx and activation of several
      kinases. While Erk/Ras activation was found to be transient, Src kinase
      phosphorylation was sustained. We have shown previously that Src kinase controls
      VEGF release from RPE cells by altering the activity of the L-type channel. We
      propose that the prolonged Src kinase activation, and its resulting effects on
      membrane depolarization and calcium influx, leads to sustained VEGF secretion. In
      addition, the previously shown effect of the autocrine positive feedback loop in
      RPE cells, involving VEGF-induced VEGF production and secretion via VEGFR-2
      receptors, will augment and prolong the effects of sublytic complement
      activation. In summary, identification of the links between oxidative stress,
      chronic, low-grade activation of the complement system, and elevated VEGF
      expression and secretion might offer opportunities to selectively inhibit
      pathological VEGF release only. 

PMID- 24664703
TI  - Inflammation in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of legal blindness in
      elderly individuals in the developed world, affecting 30-50 million people
      worldwide. AMD primarily affects the macular region of the retina that is
      responsible for the majority of central, color and daytime vision. The presence
      of drusen, extracellular protein aggregates that accumulate under the retinal
      pigment epithelium (RPE), is a major pathological hallmark in the early stages of
      the disease. The end stage 'dry' and 'wet' forms of the disease culminate in
      vision loss and are characterized by focal degeneration of the RPE and cone
      photoreceptors, and choroidal neovascularization (CNV), respectively. Being a
      multifactorial and genetically heterogeneous disease, the pathophysiology of AMD
      remains unclear, yet, there is ample evidence supporting immunological and
      inflammatory processes. Here, we review the recent literature implicating some of
      these immune processes in human AMD and in animal models.

PMID- 24664705
TI  - Inflammatory biomarkers for AMD.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness
      worldwide, affecting an estimated 50 million individuals aged over 65
      years.Environmental and genetic risk-factors implicate chronic inflammation in
      the etiology of AMD, contributing to the formation of drusen, retinal pigment
      epithelial cell dysfunction and photoreceptor cell death. Consistent with a role
      for chronic inflammation in AMD pathogenesis, several inflammatory mediators,
      including complement components, chemokines and cytokines, are elevated at both
      the local and systemic levels in AMD patients. These mediators have diverse roles
      in the alternative complement pathway, including recruitment of inflammatory
      cells, activation of the inflammasome, promotion of neovascularisation and in the
      resolution of inflammation. The utility of inflammatory biomarkers in assessing
      individual risk and progression of the disease is controversial. However,
      understanding the role of these inflammatory mediators in AMD onset, progression
      and response to treatment may increase our knowledge of disease pathogenesis and
      provide novel therapeutic options in the future.

PMID- 24664704
TI  - Impairment of the ubiquitin-proteasome pathway in RPE alters the expression of
      inflammation related genes.
AB  - The ubiquitin-proteasome pathway (UPP) plays an important role in regulating gene
      expression. Retinal pigment epithelial cells (RPE) are a major source of ocular
      inflammatory cytokines. In this work we determined the relationship between
      impairment of the UPP and expression of inflammation-related factors. The UPP
      could be impaired by oxidative stress or chemical inhibition. Impairment of the
      UPP in RPE increased the expression of several inflammatory cytokines, such as IL
      6 and IL-8. However, the expression of monocyte chemoattractant protein-1 (MCP-1)
      and complement factor H (CFH) and was reduced upon impairment of the UPP. These
      data suggest that impairment of the UPP in RPE may be one of the causes of
      retinal inflammation and abnormal functions of monocyte and the complement system
      during the pathogenesis of age-related macular degeneration. 

PMID- 24664707
TI  - Should I stay or should I go? Trafficking of sub-lytic MAC in the retinal pigment
      epithelium.
AB  - Assembly of sub-lytic C5b-9 membrane attack complexes (MAC) on the plasma
      membrane of retinal pigment epithelial cells contributes to the pathogenesis of
      age-related macular degeneration. C5b-9 pores induce calcium influx, which
      activates signaling pathways that compromise cell function. Mechanisms that limit
      sub-lytic MAC activity include: cell surface complement regulatory proteins CD46,
      CD55, and CD59 that inhibit specific steps of MAC formation; elimination of
      assembled MAC by exocytosis of membrane vesicles or by endocytosis and subsequent
      lysosomal degradation; and rapid resealing of pores by the exocytosis of
      lysosomes. Aging in the post-mitotic retinal pigment epithelium is characterized
      by the accumulation of cellular debris called lipofuscin, which has also been
      associated with retinal diseases such as age-related macular degeneration.
      Lipofuscin has been shown to activate complement components both in vitro and in
      vivo, suggesting that it could contribute complement-mediated dysfunction in the
      retinal pigment epithelium. Here, we discuss emerging evidence that vesicular
      trafficking in the retinal pigment epithelium is critical for efficient removal
      of MAC from the cell surface and for limiting inflammation in the outer retina. 

PMID- 24664706
TI  - Oxidized low-density-lipoprotein-induced injury in retinal pigment epithelium
      alters expression of the membrane complement regulatory factors CD46 and CD59
      through exosomal and apoptotic bleb release.
AB  - Genetic and immunohistochemical studies have identified the alternative
      complement pathway as an important component of age-related macular degeneration
      (AMD). The objective of this chapter is to review the impact of complement
      regulators on complement activation in the macula as it relates to AMD. Our
      laboratory and other investigators have identified CD46 and CD59 as important
      retinal pigment epithelium (RPE) cell membrane complement regulators, which are
      decreased in AMD. Using oxidized low-density lipoproteins (oxLDLs), which are
      found in Bruch's membrane in AMD, we found that CD46 and CD59 were decreased in
      RPE cells in part, by their release in exosomes and apoptotic particles. The
      release of complement regulators could potentially impair complement regulation
      on RPE cells and contribute to lesion formation in the outer retina and Bruch's
      membrane during the development of AMD. 

PMID- 24664708
TI  - Hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF)
      signaling in the retina.
AB  - Over a span of two decades, it has become increasingly clear that vascular
      endothelial growth factor (VEGF) plays an important role in the pathogenesis of
      retinal diseases including age-related macular degeneration (AMD) and diabetic
      retinopathy (DR). Based on these observations, anti-VEGF therapies are being
      developed and approved for clinical use in the treatment of neovascular eye
      diseases. Hypoxia-inducible factors (HIFs) are transcriptional factors that are
      stabilized and activated under hypoxic conditions and induce expression of gene
      products, including VEGF, that are required for cell survival under hypoxia. Here
      we discuss recent findings from our lab and others that define roles of the HIF
      VEGF axis in the retina. 

PMID- 24664709
TI  - Is age-related macular degeneration a microvascular disease?
AB  - Age-related macular degeneration (AMD) is a common, degenerative disease of the
      central retina affecting millions of elderly in the USA alone and many more
      worldwide. A better understanding of the pathophysiology of AMD will be essential
      for developing new treatments. In this review, we discuss the potential impact of
      complement complex deposition at the choriocapillaris of aging eyes and the
      relationship between choriocapillaris loss and drusen formation. We further
      propose a model that integrates genetic and anatomical findings in AMD and
      suggest the implications of these findings for future therapies. 

PMID- 24664710
TI  - Genetic risk models in age-related macular degeneration.
AB  - Late-stage age-related macular degeneration (AMD) is a common sight-threatening
      disease of the central retina affecting approximately 1 in 30 Caucasians. Besides
      age and smoking, common genetic variants from at least 19 gene loci have
      reproducibly been associated with AMD likely explaining a large proportion of
      disease. Based on the current knowledge, several models were calculated to
      predict disease risk each with its own strength and weakness. Here, we review and
      compare published genetic risk models for AMD with or without additionally
      accounting for non-genetic factors. 

PMID- 24664711
TI  - A mechanistic review of cigarette smoke and age-related macular degeneration.
AB  - Age-related macular degeneration (AMD), a complex disease stemming from both
      genetic abnormalities and environmental insults, is the most common form of
      visual impairment in elderly individuals of the Western world. Many potential
      etiologies are linked to AMD, but smoking is the leading environmental insult
      associated with this maculopathy. Smoke-induced damage is mediated in part
      through direct oxidation, depletion of antioxidants, complement activation, and
      vascular transmutations. Clinically, these mechanisms manifest themselves as
      keystones of atrophic AMD: retinal pigment epithelium degeneration, formation of
      extracellular deposits such as drusen, and thickening of Bruch's membrane.
      Furthermore, smoking induces angiogenesis and choroidal neovascularization,
      advancing the course of the disease to late-stage AMD. Further exploration of the
      biological processes affected by cigarette smoke exposure will provide greater
      insight into the pathogenesis of AMD. 

PMID- 24664712
TI  - Measuring cone density in a Japanese macaque (Macaca fuscata) model of age
      related macular degeneration with commercially available adaptive optics.
AB  - The aim of this study was to assess the feasibility of using a commercially
      available high-resolution adaptive optics (AO) camera to image the cone mosaic in
      Japanese macaques (Macaca fuscata) with dominantly inherited drusen. The macaques
      examined develop drusen closely resembling those seen in humans with age-related
      macular degeneration (AMD). For each animal, we acquired and processed images
      from the AO camera, montaged the results into a composite image, applied custom
      cone-counting software to detect individual cone photoreceptors, and created a
      cone density map of the macular region. We conclude that flood-illuminated AO
      provides a promising method of visualizing the cone mosaic in nonhuman primates.
      Future studies will quantify the longitudinal change in the cone mosaic and its
      relationship to the severity of drusen in these animals. 

PMID- 24664713
TI  - Nuclear receptors as potential therapeutic targets for age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is the most important cause of blindness
      and visual impairment among the elderly. Nuclear receptors represent one of the
      largest families of transcription factors, with 48 present in the human genome.
      They are critical regulators and modulators of developmental and physiological
      processes and are both targets of drugs and chemicals of environmental
      significance. Many of the cellular processes regulated by nuclear receptors are
      disrupted in AMD. With this in mind, we recently created a nuclear receptor atlas
      of retinal pigment epithelial (RPE) cells, cells affected in AMD, highlighting
      the expression of all the nuclear receptors. The results of which provided
      scaffold to study individual receptors in aging and disease. This study led to
      several candidate receptors that have become the focus of detailed studies
      regarding their mechanistic role in the eye. One example of a nuclear receptor
      potentially relevant to AMD pathobiology is presented. 

PMID- 24664714
TI  - Utilizing stem cell-derived RPE cells as a therapeutic intervention for age
      related macular degeneration.
AB  - PURPOSE: Degeneration or dysfunction of the retinal pigment epithelium (RPE) can
      induce secondary photoreceptor atrophy and catastrophic vision loss in patients
      with age-related macular degeneration (AMD). AMD is the leading cause of vision
      loss in the elderly in industrialized countries and no cure exists for the "dry"
      or atrophic form to date. However, recent pre-clinical data from several groups
      suggests that embryonic stem cell-derived RPE cell transplantation may prevent
      photoreceptor degeneration in animal models of RPE degeneration. Another approach
      may be to derive RPE cells from autologous induced pluripotent stem cells (iPSCs)
      reprogrammed from dermal tissue. However, the safety of this approach has been
      questioned on several levels. In this chapter we will summarize work reported by
      several groups, including our own, that clearly demonstrate that transplanted RPE
      cells can provide anatomical and functional photoreceptor rescue in animal models
      of retinal degeneration. We will also discuss some of the prevailing concerns and
      challenges associated with this technique.

PMID- 24664715
TI  - Microglia-Muller cell interactions in the retina.
AB  - Microglia and Muller cells are cell types that feature prominently in responses
      to disease and injury in the retina. However, their mutual interactions have not
      been investigated in detail. Here, we review evidence that indicate that these
      two cell populations exchange functionally significant signals under uninjured
      conditions and during retinal inflammation. Under normal conditions, Muller cells
      constitute a potential source of extracellular ATP that mediates the activity
      dependent regulation of microglial dynamic process motility. Following microglial
      activation in inflammation, microglia can signal to Muller cells, influencing
      their morphological, molecular, and functional responses. Microglia-Muller cell
      interactions appear to be a mode of bi-directional communications that help shape
      the overall injury response in the retina. 

PMID- 24664716
TI  - Isolation and ex vivo characterization of the immunophenotype and function of
      microglia/macrophage populations in normal dog retina.
AB  - Microglia are the primary resident immune cells of the retina and are involved in
      the pathogenesis of various retinal diseases. In this study, we optimized
      experimental conditions to isolate microglia from canine retinas and
      characterized ex vivo their immunophenotype and function using flow cytometry
      (FACS). The most suitable protocol included a mechanical dissociation of the
      retina and an enzymatic digestion using DNAse and collagenase. Extraction was
      carried out by density gradient centrifugation, and retinal microglia accumulated
      on distinct interfaces of 1.072 and 1.088 g/mL of a Percoll gradient.
      Immunophenotypical characterization was performed with monoclonal antibodies
      CD11b, CD11c, CD18, CD45, CD44, B7-1 (CD80), B7-2 (CD86), CD1c, ICAM-1 (CD54),
      CD14, MHCI, MHCII, CD68, CD3, CD4, CD8alpha, and CD21. The most prevalent
      microglia population in the normal canine retina is CD11b(high)CD45(low).
      Functionally, retinal microglia exhibited phagocytosis and reactive oxygen
      species (ROS) generation activities. To conclude, ex vivo examinations of retinal
      microglia are feasible and possibly reflect the in vivo conditions, avoiding
      artifacts observed in tissue culture. The established method will be relevant to
      examine microglia from diseased canine retinas in order to elucidate their roles
      in degenerative processes. 

PMID- 24664717
TI  - Muller cells and microglia of the mouse eye react throughout the entire retina in
      response to the procedure of an intravitreal injection.
AB  - The animal model of N-methyl-D-aspartate (NMDA)-induced excitotoxic damage of
      retinal ganglion cells (RGC) is widely used to study the molecular mechanisms of
      RGC death and/or its prevention by neuroprotective agents. NMDA is typically
      applied by intravitreal injection, while contralateral control eyes are treated
      by the injection of PBS as vehicle. Herein we report that the procedure of an
      intravitreal injection alone is sufficient to cause substantial reactive changes
      in Muller cells and microglia throughout the entire retina. Six week old CD1 mice
      received a single intravitreal injection of PBS or NMDA. Immunohistochemistry
      showed the presence of reactive microglia and Muller cells in both NMDA- and PBS
      treated eyes during the first 24 h after injection. After 7 days, the reactive
      changes were only present in NMDA-injected eyes, but no longer in PBS-treated
      eyes. Investigators using intravitreal injections in the mouse eye should be
      aware that vehicle-injected control eyes will undergo phenotypic changes in
      microglia and Muller glia, and are likely to behave differently in their biology
      when compared with uninjected eyes, at least within the first 24 h after
      experiment. 

PMID- 24664719
TI  - Ambiguous role of glucocorticoids on survival of retinal neurons.
AB  - Glucocorticoids (GCs) have a wide range of functions on several mammalian cell
      types, most of which are aimed at boosting survival, which is the raison d'etre
      of the acute stress response. The role GCs play in the survival and viability of
      neurons is incongruous, as studies have revealed neuroprotective as well as
      neurodegenerative effects. These effects seem to depend on multiple factors
      amongst which are; the cell type involved, the mode of injury or underlying cause
      of cell death, likewise the concentration and or duration of GC exposure.In this
      mini review, we discuss mechanisms of GC action and their effect on
      neurodegeneration in general, and specifically review the effect of GCs on
      retinal neurons, in animal models of retinal degeneration or acute neuronal
      damage. Finally, we summarize potential protective and harmful GC-mediated
      mechanisms, which might be involved in the determination of neuronal fate in the
      retina following injury or during degeneration. 

PMID- 24664718
TI  - Subretinal infiltration of monocyte derived cells and complement misregulation in
      mice with AMD-like pathology.
AB  - We have characterized a naturally-occurring mutation in mice that causes slow,
      progressive photoreceptor degeneration, white fundus flecks, and late-onset RPE
      atrophy. These animals predictably lose visual function as photoreceptors
      degenerate. Genetic studies identified a deletion in the 5' coding sequence of
      Mfrp, designated Mfrp (174delG) , which essentially results in a complete
      knockout at the protein level. We have shown in Mfrp (174delG) mice that these
      white fundus flecks are due to the presence of F4/80+ inflammatory cells in the
      subretinal space. Here we expand on our initial description of the cells with
      additional markers and by determining their origin. We have also begun an
      analysis of complement factors in the RPE and found decreased levels of C3d,
      suggesting that the alternative complement pathway may be misregulated. Finally,
      we compare and contrast the characteristics of fundus images in Mfrp (174delG)
      mice with those of other mutations that cause similar irregularities, including
      Crb1 (rd8) and RDH5, and discuss the structural differences that may underlie
      them. 

PMID- 24664720
TI  - Microglia-Muller glia crosstalk in the rd10 mouse model of retinitis pigmentosa.
AB  - Retinitis pigmentosa refers to a large, genetically heterogeneous group of
      retinal dystrophies. This condition is characterized by the gradual onset of
      blindness due to progressive deterioration of the retina, a process that includes
      photoreceptor and retinal-pigmented-epithelium cell decay and death, microglial
      recruitment, reactive gliosis, and vascular disorganization and regression. We
      found that early in the degenerative process, the rd10 mouse retina exhibits high
      levels of photoreceptor cell death and reactive Muller gliosis. In explant
      cultures, both degenerative processes were abrogated by IGF-I treatment.
      Moreover, the beneficial effect of IGF-I was diminished by microglial depletion
      using clodronate-containing liposomes. Interestingly, in the absence of IGF-I,
      microglial depletion partially prevented cell death without affecting Muller
      gliosis. These findings strongly suggest a role for microglia-Muller glia
      crosstalk in neuroprotection. However, a subpopulation of microglial cells
      appears to promote neurodegeneration in the dystrophic retina. Our findings
      indicate that beneficial neuroprotective effects may be achieved through
      strategies that modulate microglial cell responses. 

PMID- 24664721
TI  - The neuroprotective potential of retinal Muller glial cells.
AB  - Retinal Muller glial cells (RMG) are recognized as essential players providing
      neurotrophic, metabolic and structural support for retinal neurons as well as
      mediating inflammatory responses in the retina. While some key neuroprotective
      molecules in the context of retinal degeneration, such as FGF2, LIF, PEDF have
      been demonstrated to be of RMG origin, there is yet no comprehensive
      understanding on the multifaceted role of RMG in orchestrating diverse
      intercellular functions. In order to systematically as well as functionally
      analyse RMG reactivity to retinal degeneration and thus explore the RMG-derived
      signalling molecules in depth, we combined genomics and proteomics approaches
      based on profiling primary RMGs from mouse and pig. However, since modulations in
      cell to cell communication by secretion of molecules may not necessarily present
      with changes in the mRNA profile, we developed shotgun proteomics approaches
      enabling direct protein profiling of the RMG lysates and secretomes using label
      free and SILAC quantitations. We have identified a pool of novel proteins
      relevant for pro-survival effects transmitted from RMG to retinal neurons and
      functionally valdidated selected molecules. Additionally, our approach allows to
      identify RMG reactions to intrinsic and extrinsic stimuli and thus enables to
      molecularly dissect RMG reactivity relevant for retinal health and disease. 

PMID- 24664722
TI  - Leukemia inhibitory factor signaling in degenerating retinas.
AB  - Degeneration of cells in the retina is a hallmark of various inherited and
      acquired blinding diseases in humans. One of the most challenging problems to
      establish successful treatments for these diseases is to understand the molecular
      mechanisms that result in retinal degeneration and to identify endogenous rescue
      pathways which support cell survival. In many mouse models for retinal
      degeneration, expression of LIF in glial cells in response to a disease condition
      is crucial for the activation of an elaborate protective system. This mini review
      will summarize the findings that are related to LIF signaling and discuss the
      neuroprotective effects of LIF in different animal models. 

PMID- 24664723
TI  - In vivo function of the ER-Golgi transport protein LMAN1 in photoreceptor
      homeostasis.
AB  - LMAN1 is a type I transmembrane protein that selectively transports its cargo
      proteins from ER to ER-Golgi intermediate compartment (ERGIC) and Golgi. Lman1 is
      a direct target of the transcription factor NRL in mouse retina. Therefore, we
      examined the in vivo function of LMAN1 in retina. Although Lman1 (- / -) mouse
      eyes did not show abnormality in histology and electroretinogram analysis at 3
      months, Lman1 (- / -) retina at 6 months showed a decrease in cis-Golgi markers
      GM130 and GRASP65. We also observed abnormal level and location of Rhodopsin in
      these mice. Taken together, LMAN1 may play a role in photoreceptor gene transport
      and homeostasis. 

PMID- 24664724
TI  - Investigating the role of retinal Muller cells with approaches in genetics and
      cell biology.
AB  - Muller cells are major macroglia and play many essential roles as a supporting
      cell in the retina. As Muller cells only constitute a small portion of retinal
      cells, investigating the role of Muller glia in retinal biology and diseases is
      particularly challenging. To overcome this problem, we first generated a Cre/lox
      based conditional gene targeting system that permits the genetic manipulation and
      functional dissection of gene of interests in Muller cells. To investigate
      diabetes-induced alteration of Muller cells, we recently adopted methods to
      analyze Muller cells survival/death in vitro and in vivo. We also used normal and
      genetically altered primary cell cultures to reveal the mechanistic insights for
      Muller cells in biological and disease processes. In this article, we will
      discuss the applications and limitations of these methodologies, which may be
      useful for research in retinal Muller cell biology and pathophysiology. 

PMID- 24664725
TI  - An overview of the involvement of interleukin-18 in degenerative retinopathies.
AB  - Age-related macular degeneration (AMD) is the leading cause of central vision
      loss worldwide and while polymorphisms in genes associated with the immune system
      have been identified as risk factors for disease development, the underlying
      pathways and mechanisms involved in disease progression have remained unclear. In
      AMD, localised inflammatory responses related to particulate matter accumulation
      and subsequent "sterile" inflammation has recently gained considerable interest
      amongst basic researchers and clinicians alike. Typically, inflammatory responses
      in the human body are caused as a result of bacterial or viral infection, however
      in chronic conditions such as AMD, extracellular particulate matter such as
      drusen can be "sensed" by the NACHT, LRR and PYD domains-containing protein 3
      (NLRP3) inflammasome, culminating in the release of the two pro-inflammatory
      cytokines IL-1beta and IL-18 in the delicate local tissue of the retina.
      Identification at the molecular level of mediators of the inflammatory response
      in AMD may yield novel therapeutic approaches to this common and often severe
      form of blindness. Here, we will describe the role of IL-18 in AMD and other
      forms of retinal disorders. We will outline some of the key functions of IL-18 as
      it pertains to maintaining tissue homeostasis in a healthy and
      degenerating/diseased retina. 

PMID- 24664726
TI  - Chronic intraocular inflammation and development of retinal degenerative disease.
AB  - Elevated levels of inflammatory cytokines in the vitreous of patients with
      chronic intraocular inflammatory (uveitis) have long been suspected to contribute
      to the pathogenesis of retinal degenerative diseases. However, direct connection
      between chronic inflammation and development of retinal degenerative diseases has
      been difficult to establish because we lack an appropriate animal model of co
      existing chronic intraocular inflammation and neurodegeneration. This report
      discusses new developments in immunological and diabetic research that suggest
      that persistent secretion of pro-inflammatory cytokines during uveitis might
      induce insulin resistance and retinal degenerative changes that contribute to the
      pathogenesis of Diabetic Retinopathy (DR), a retinal dystrophy of significant
      public health importance. 

PMID- 24664727
TI  - The relevance of chemokine signalling in modulating inherited and age-related
      retinal degenerations.
AB  - Systemic monocytes, tissue resident macrophages, dendritic cells and microglia
      have specific roles in immune surveillance and maintenance of tissue homeostasis
      and are key regulator and effector cells of the local immune response to acute
      and chronic tissue injury.Two major signalling pathways that differentially
      define trafficking behaviour and activation of systemic and local myeloid cell
      populations in response to exogenous and endogenous inflammatory stimuli are the
      Ccl2-Ccr2 and the Cx3cl1-Cx3cr1 chemokine pathways.Alterations in these pathways
      have been implicated in controlling myeloid cell activation during normal ageing
      and in age-related retinal degenerations, including age-related macular
      degeneration (AMD).We review the evidence for how altered chemokine signalling in
      acute and chronic inflammatory conditions regulate local and systemic myeloid
      cell responses in the retina and how this may contribute to or attenuate
      pathology in inherited and age-related retinal diseases. We discuss the role of
      environmental factors (e.g. light exposure) and the influence of genetic factors
      on the manifestation of pathology in experimental models and in human patients
      and how we envisage harnessing this knowledge for the development of targeted,
      more broadly applicable anti-inflammatory treatment strategies for a wide range
      of retinal degenerations. 

PMID- 24664728
TI  - The complement regulatory protein CD59: insights into attenuation of choroidal
      neovascularization.
AB  - Complement activation is associated with age-related macular degeneration (AMD),
      with the retinal pigment epithelium (RPE) being one of the main target tissues.
      In AMD, disease severity is correlated with the formation of the membrane attack
      complex (MAC), the terminal step in the complement cascade, as well as diminished
      RPE expression of CD59, a membrane-bound regulatory protein of MAC formation.
      This has prompted the search for therapeutic strategies based on MAC inhibition,
      and soluble forms of CD59 (sCD59) have been investigated in mouse laser-induced
      choroidal neovascularization, a model for "wet" AMD. Unlike membrane-bound CD59,
      sCD59 provides relatively poor cell protection from complement, and different
      strategies to increase sCD59 activity at the cell membrane level have been
      investigated. These include increasing the circulatory half-life of sCD59 by the
      addition of an Fc moiety; increasing the half-life of sCD59 in target tissues by
      modifying CD59 with a (non-specific) membrane-targeting domain; and by locally
      overexpressing sCD59 via adenoviral vectors. Finally, a different strategy
      currently under investigation employs complement receptor (CR)2-mediated
      targeting of CD59 exclusively to membranes under complement attack. CR2
      recognizes long-lasting membrane-bound breakdown activation fragments of
      complement C3. CR2-CD59 may have greater therapeutic potential than other
      complement inhibitory approaches, since it can be administered either
      systemically or locally, it will bind specifically to membranes containing
      activated complement activation fragments, and dosing can be regulated. Hence,
      this strategy might offer opportunities for site-specific inhibition of
      complement in diseases with restricted sites of inflammation such as AMD. 

PMID- 24664729
TI  - Regeneration-associated genes on optic nerve regeneration in fish retina.
AB  - It has been well documented that fish central nervous system, including retina
      and optic nerve, can regenerate and recover its function after nerve injury.
      Within a few decades, a number of regeneration-associated genes (RAGs) have been
      identified in fish retina following optic nerve injury (ONI). RAGs can be
      classified into two groups: cell survival- and axonal outgrowth-related genes. In
      fish retina after ONI, cell survival-related genes were upregulated in 1-6 days
      after ONI, which corresponds to the preparation stage for cell survival and
      axonal sprouting. Subsequently, axonal outgrowth-related genes were upregulated
      in 1-6 weeks after ONI, which corresponds to the axonal regrowth stage. Recently,
      we've found a novel type of RAGs, dedifferentiation-related genes, that are
      upregulated in overlapping time between cell survival and axonal regrowth (3-10
      days after ONI). In this chapter we summarize these three types of RAGs that
      promote optic nerve regeneration in the fish retina after ONI. 

PMID- 24664730
TI  - Dominant Stargardt Macular Dystrophy (STGD3) and ELOVL4.
AB  - Autosomal dominant Stargardt3 Macular Dystrophy (STGD3) results from mutations in
      the ELOVL4 gene. ELOVL4 protein localizes to the endoplasmic reticulum (ER),
      where it mediates the rate-limiting condensation reaction during very long-chain
      (VLC, >=  C28) fatty acid biosynthesis. The defective gene product is truncated
      at the C-terminus, leading to mislocalization and aggregation in other
      organelles. In this review, we summarize our current understanding of the disease
      causing mutation and its potential role in STGD3 pathogenesis. 

PMID- 24664732
TI  - Expression of poly(ADP-ribose) glycohydrolase in wild-type and PARG-110 knock-out
      retina.
AB  - Poly(ADP-ribose) (PAR) turnover is required for many cellular processes, and
      highly relevant for cell death and survival. This post-translational protein
      modification is regulated by the synthesizing enzyme poly(ADP)ribose-polymerase
      (PARP) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG).
      Previously, PARP activity was found to be involved in photoreceptor degeneration
      in the rd1 mouse and in rd1-like conditions PARP-1 was the main PARP family
      member contributing to photoreceptor cell death. Despite the manifest role of
      PARP and PAR accumulation in photoreceptor cell death, the influence of PAR
      degradation on photoreceptor viability was still unknown. Here, we investigated
      the role of PARG in photoreceptor degeneration using the PARG-110 knock out mouse
      and report for the first time on PARG expression in wild-type and knock-out
      retina. 

PMID- 24664731
TI  - Modulation of the rate of retinal degeneration in T17M RHO mice by reprogramming
      the unfolded protein response.
AB  - The goal of this study is to validate whether reprogramming of the UPR via
      modulation of pro-apoptotic caspase-7 and CHOP proteins could be an effective
      approach to slow down the rate of retinal degeneration in ADRP mice. In order to
      pursue our goal we created the T17M RHO CASP7 and T17M RHO CHOP mice to study the
      impact of the CASP7 or CHOP ablations in T17M RHO retina by ERG, SD-OCT,
      histology and western blot analysis. The scotopic ERG demonstrated that the
      ablation of the CASP7 in T17M RHO retina leads to significant preservation of the
      function of photoreceptors compared to control. Surprisingly, the ablation of pro
      apoptotic CHOP protein in T17M RHO mice led to a more severe form of retinal
      degeneration. Results of the SD-OCT and histology were in agreement with the ERG
      data. The further analysis demonstrated that the preservation of the structure
      and function or the acceleration of the onset of the T17M RHO photoreceptor
      degeneration occurred via reprogramming of the UPR. In addition, the CASP7
      ablation leads to the inhibition of cJUN mediated apoptosis, while the ablation
      of CHOP induces an increase in the HDAC. Thus, manipulation with the UPR requires
      careful examination in order to achieve a therapeutic effect. 

PMID- 24664733
TI  - Current therapeutic strategies for P23H RHO-linked RP.
AB  - The first autosomal dominant mutation identified to cause retinitis pigmentosa in
      the North American population was the substitution of proline to histidine at
      position 23 of the rhodopsin gene (P23H RHO). Many biochemical studies have
      demonstrated that P23H mutation induces rhodopsin (RHO) misfolding leading to
      endoplasmic reticulum stress. Herein, we review current thinking of this topic. 

PMID- 24664735
TI  - Unc119 gene deletion partially rescues the GRK1 transport defect of Pde6d (- /-)
      cones.
AB  - PrBP/delta, encoded by the Pde6d gene, is an isoprenyl-binding protein that
      regulates trafficking of isoprenylated proteins, such as PDE6 and GRK1, from
      photoreceptor inner segments to outer segments. Trafficking of PDE6 and GRK1 to
      photoreceptor outer segments is impeded in Pde6d knockout mice. In Pde6d (-/-)
      cones, PDE6 and GRK1 are nearly undetectable and the b-wave amplitudes of
      photopic ERGs in Pde6d (-/-) mice are reduced by over 50 %. We reported recently
      that UNC119, a homolog of PrBP/delta highly expressed in photoreceptors,
      functions as an acyl-binding protein and regulates transport of G-proteins in
      sensory neurons. Since both PrBP/delta and UNC119 regulate peripheral protein
      trafficking in photoreceptors, we generated Pde6d; Unc119 double knockout mice in
      order to study how PrBP/delta and UNC119 may interact. Surprisingly, knockout of
      Unc119 partially reversed the transport defect of GRK1 in cone photoreceptors
      caused by deletion of Pde6d, and the b-wave amplitudes of photopic ERGs in the
      double knockout mice were significantly higher than those in the Pde6d (-/-)
      mice. These results suggest that cone transport of isoprenylated and acylated
      proteins is interdependent. 

PMID- 24664734
TI  - Pathogenesis of X-linked RP3: insights from animal models.
AB  - Retinitis Pigmentosa (RP) is a genetically heterogeneous disorder characterized
      by rod and cone photoreceptor cell dysfunction. X-linked RP (XLRP) is one of the
      most severe forms of human retinal degeneration, as determined by age-of-set and
      progression, and accounts for six to 20 % of all RP cases. At least six XLRP loci
      have been identified, but RP3 is the major subtype of XLRP, accounting for 70 to
      80 % of affected families. The RPGR gene is responsible for the RP3 form of XLRP
      and is mutated in 10-20 % of all RP patients. The pathogenesis of retinitis
      pigmentosa GTPase regulator (RPGR) mutant-causing RP is not clear, different
      animal models have been used to understand the pathogenesis of these diseases. In
      this brief review, we will summarize the functional characterization of RPGR and
      highlight recent studies in animal models, which will not only shed light on the
      disease mechanisms in XLRP but will also provide therapeutic strategies for RP
      treatment.

PMID- 24664736
TI  - Retinal function in aging homozygous Cln3 (Deltaex7/8) knock-in mice.
AB  - Neuronal ceroid lipofuscinoses (NCL) are characterized by lysosomal accumulation
      of autofluorescent material and lead to degeneration of the central nervous
      system. Patients affected by the juvenile form of NCL (JNCL), the most common
      form of the disease, develop visual failure prior to mental and motor deficits.
      It is currently unclear if the corresponding mouse model, Cln3 (Deltaex7/8) knock
      in, develops the same retinal phenotype and electroretinogram (ERG) measurements
      as affected patients. The aim of our study was to investigate the visual disease
      progression in the Cln3 (Deltaex7/8) mice using scotopic and photopic ERGs as
      well as optokinetic tracking (OKT) at different ages. The results were then
      compared with age-matched controls.The amplitudes of the a-wave and b-wave
      (scotopic ERG) decrease significantly in Cln3 (Deltaex7/8) mice starting at the
      age of 12 months. A reduction in the b/a-amplitude ratio indicates a degeneration
      preferentially of the inner retina. An amplitude reduction observed in the Cln3
      (+/+) control mice may be attributed to an additional Crb1 (rd8) mutation. Using
      optokinetic tracking (OKT) the Cln3 (Deltaex7/8) mice show a progressive decline
      in visual acuity after 12 months of age. 

PMID- 24664737
TI  - Synergistic interaction of tubby and tubby-like protein 1 (Tulp1).
AB  - Mutations in either tubby or tubby-like protein 1 (Tulp1) cause retinal
      degeneration with undefined mechanisms. We recently identified both proteins with
      unconventional secretion as novel MerTK-specific phagocytosis ligands for retinal
      pigment epithelium (RPE) cells. Using our newly-developed open reading frame
      (ORF) phage display as a technology for protein-protein interactions, we
      identified Tulp1 as a Tubby-binding protein. The interaction of tubby and Tulp1
      was verified by yeast two-hybrid and protein pull-down assays. Tubby and Tulp1
      form heterodimer or heterooligomer and their interaction was functionally
      revealed by their synergistic stimulation of RPE phagocytosis. Tubby and Tulp1
      mediated phagocytosis through MerTK-dependent signaling with non-muscle myosin II
      redistribution leading to colocalization of phagocytosed vesicles with rearranged
      NMMIIA. 

PMID- 24664738
TI  - Interaction of tubby-like protein-1 (Tulp1) and microtubule-associated protein
      (MAP) 1A and MAP1B in the mouse retina.
AB  - Tubby-like protein-1 (Tulp1) is a photoreceptor-specific protein involved in the
      transport of specific proteins from the inner segment (IS) to the outer segment
      (OS) in photoreceptor cells. Mutations in the human TULP1 gene cause an early
      onset form of retinitis pigmentosa. Our previous work has shown an association
      between Tulp1 and the microtubule-associated protein, MAP1B. An allele of Mtap1a,
      which encodes the MAP1A protein, significantly delays photoreceptor degeneration
      in Tulp1 mutant mice. MAP1 proteins are important in stabilizing microtubules in
      neuronal cells, but their role in photoreceptors remains obscure. To investigate
      the relationship between Tulp1 and MAP1 proteins, we performed western blots,
      immunoprecipitations (IP), immunohistochemistry and proximity ligand assays (PLA)
      in wild-type and tulp1-/- mouse retinas. Our IP experiments provide evidence that
      Tulp1 and MAP1B interact while PLA experiments localize their interaction to the
      outer nuclear layer and IS of photoreceptors. Although MAP1A and MAP1B protein
      levels are not affected in the tulp1-/- retina, they are no longer localized to
      the OS of photoreceptors. This may be the cause for disorganized OSs in tulp1-/-
      mice, and indicate that their transport to the OS is Tulp1-dependent. 

PMID- 24664739
TI  - CEP290 and the primary cilium.
AB  - The protein CEP290 has recently emerged as a major player in the biology of the
      cilium and as a causative protein in a number of human syndromic diseases, most
      of which are associated with the devastating blinding disease Leber congenital
      amaurosis. (Coppieters et al., Hum Mutat 31, 2010, 1097-1108) CEP290 is known to
      be an important component of the primary cilium, localizing to the Y-links of the
      ciliary transition zone and having a role in the regulation of transport in and
      out of the ciliary compartment (Craige et al., J Cell Biol 190, 2010, 927-940).
      While many mutations in CEP290 have been identified in human patients, how these
      mutations result in the spectrum of human disease attributed to the protein
      remain unknown. As we begin to learn more about the normal role of CEP290, it is
      likely that we will begin to shed light on how these mutations result in the
      various CEP290 disease phenotypes. Here we discuss many of these diverse aspects
      of CEP290 biology and pathology in an attempt to link what we know about the
      molecular mechanisms of CEP290 function with what we know about CEP290-associated
      disease.

PMID- 24664740
TI  - Usher syndrome protein network functions in the retina and their relation to
      other retinal ciliopathies.
AB  - The human Usher syndrome (USH) is the most frequent cause of combined hereditary
      deaf-blindness. USH is genetically and clinically heterogeneous: 15 chromosomal
      loci assigned to 3 clinical types, USH1-3. All USH1 and 2 proteins are organized
      into protein networks by the scaffold proteins harmonin (USH1C), whirlin (USH2D)
      and SANS (USH1G). This has contributed essentially to our current understanding
      of the USH protein function in the eye and the ear and explains why defects in
      proteins of different families cause very similar phenotypes. Ongoing in depth
      analyses of USH protein networks in the eye indicated cytoskeletal functions as
      well as roles in molecular transport processes and ciliary cargo delivery in
      photoreceptor cells. The analysis of USH protein networks revealed molecular
      links of USH to other ciliopathies, including non-syndromic inner ear defects and
      isolated retinal dystrophies but also to kidney diseases and syndromes like the
      Bardet-Biedl syndrome. These findings provide emerging evidence that USH is a
      ciliopathy molecularly related to other ciliopathies, which opens an avenue for
      common therapy strategies to treat these diseases. 

PMID- 24664741
TI  - The phenotype of the good effort mutant zebrafish is retinal degeneration by cell
      death and is linked to the chromosome assembly factor 1b gene.
AB  - In a screen to identify zebrafish eye mutants, we isolated the good effort (gef)
      mutant. The retina of gef embryos is characterized by the successful initiation
      of the optic primordium and normal retinal development over the first 2 days post
      fertilization (dpf). The mutant retina, however, fails to continue to grow.
      Embryos from gef heterozygous incrosses were analyzed for cell death by acridine
      orange and by TUNEL labeling at 2 dpf. Significantly more TUNEL-positive and
      acridine orange-labeled dying cells were found in gef mutant embryos at 2 dpf
      relative to wild-type embryos. Because this time was earlier than any observable
      gross morphological differences, this cell death was likely the cause of the
      gross morphological defects. Meiotic mapping localized the mutation interval to a
      one-megabase interval on zebrafish chromosome 9. 

PMID- 24664742
TI  - Knock-down DHDDS expression induces photoreceptor degeneration in zebrafish.
AB  - A mutation in the dehydrodolichol diphosphate synthase (DHDDS) was recently
      identified as the cause of a subtype of recessive retinitis pigmentosa (RP).
      Molecular modeling indicates that this mutation could result in low enzymatic
      efficiency of DHDDS. To investigate the possible link between insufficient DHDDS
      activity and photoreceptor degeneration, the expression of DHDDS was knocked down
      by morpholino oligonucleotides (MO) injected into zebrafish one cell embryos. The
      general appearance and behavior of 4-day-old MO-injected fish were normal, but
      they failed to respond to light-off, suggesting loss of visual function.
      Morphological analysis showed that photoreceptor outer segments in retinas of MO
      injected fish are very short and in many cases completely missing. Peanut
      agglutinin (PNA) staining confirmed the absence of cone outer segments. These
      results demonstrate that suppression of DHDDS expression in zebrafish leads to
      the loss of photoreceptor outer segments and visual function. These results
      support the hypothesis that insufficient DHDDS function leads to retinal
      degeneration. 

PMID- 24664743
TI  - Spectral domain optical coherence tomography findings in CNGB3-associated
      achromatopsia and therapeutic implications.
AB  - We describe the spectral domain OCT findings in two siblings with CNGB3
      associated achromatopsia. A 33-year-old female and her 31-year-old sibling were
      evaluated for mild nystagmus and decreased visual acuity which had been present
      since childhood. They were each evaluated with full field Ganzfeld
      electroretinography which demonstrated flat photopic responses and preserved rod
      function. Genetic testing performed at Carver lab at the University of Iowa
      confirmed a diagnosis of achromatopsia with identical mutations in the CNGB3
      gene. Spectral domain optical coherence tomography was performed which revealed
      foveal changes in both siblings, with slight phenotypic variations in these
      genotypically identical siblings. OCT findings in achromatopsia emphasize the
      importance of early identification and treatment in this disorder. 

PMID- 24664744
TI  - Photoreceptor pathology in the X-linked retinoschisis (XLRS) mouse results in
      delayed rod maturation and impaired light driven transducin translocation.
AB  - Light-activated movement of transducin-alpha (Galphat1) from rod photoreceptor
      outer segments (ROS) into inner segments (IS) enables rods to rapidly adapt to
      changes in light intensity. The threshold light intensity at which Galphat1
      translocates from ROS into IS is primarily determined by the rates of activation
      and inactivation of Galphat1. Loss- of- expression of the retina specific cell
      surface protein, retinoschsin (Rs1-KO), led to a dramatic 3-10 fold increase,
      depending on age, in the luminance threshold for transducin translocation from
      ROS into IS compared with wild-type control. In contrast, arrestin translocated
      from IS into ROS at the same light intensity both in WT and Rs1-KO mice.
      Biochemical changes, including reduced transducin protein levels and enhanced
      transducin GTPase activity, explain the shift in light intensity threshold for
      Galphat1 translocation in Rs1-KO mice. These changes in Rs1-KO mice were also
      associated with age related alterations in photoreceptor morphology and
      transcription factor expression that suggest delayed photoreceptor maturation. 

PMID- 24664745
TI  - Mouse models for cone degeneration.
AB  - Loss of cone vision has devastating effects on everyday life. Even though much
      effort has been made to understand cone physiology and pathophysiology, no
      successful therapies are available for patients suffering from cone disorders. As
      complex retinal interactions cannot be studied in vitro, utilization of different
      animal models is inevitable. Due to recent advances in transgenesis, mice became
      the most popular animal model to study human diseases, also in ophthalmology.
      While there are similarities in retinal anatomy and pathophysiology between mice
      and humans, there are also differences, most importantly the lack of a cone-rich
      macula in mice. Instead, cones in mice are rare and distributed over the whole
      retina, which makes the analysis of cone pathophysiology very difficult in these
      animals. This hindrance is one of the reasons why our understanding of rod
      pathophysiological processes is much more advanced. Recently, however, the
      sparseness of cones was overcome by the generation of the Nrl (- / -) mouse that
      expresses only cone photoreceptors in the retina. This paper will give a brief
      overview of some of the known mouse models to study cone degeneration and discuss
      the current knowledge gained from the analysis of these models. 

PMID- 24664746
TI  - How long does a photoreceptor cell take to die? Implications for the causative
      cell death mechanisms.
AB  - The duration of cell death may allow deducing the underlying degenerative
      mechanism. To find out how long a photoreceptor takes to die, we used the rd1
      mouse model for retinal neurodegeneration, which is characterized by
      phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high
      cGMP levels. Based on cellular data on the progression of cGMP accumulation, cell
      death, and survival, we created a mathematical model to simulate the temporal
      development of the degeneration and the clearance of dead cells. Both cellular
      data and modelling suggested that at the level of the individual cell, the
      degenerative process was rather slow, taking around 80 h to complete. Organotypic
      retinal explant cultures derived from wild-type animals and exposed to the
      selective PDE6 inhibitor zaprinast, confirmed the surprisingly long duration of
      an individual photoreceptor cell's death. We briefly discuss the possibility to
      link different cell death stages and their temporal progression to specific
      enzymatic activities known to be causally connected to cell death. This in turn
      opens up new perspectives for the treatment of inherited retinal degeneration,
      both in terms of therapeutic targets and temporal windows-of-opportunity. 

PMID- 24664747
TI  - Endoplasmic reticulum stress in vertebrate mutant rhodopsin models of retinal
      degeneration.
AB  - Rhodopsin mutations cause many types of heritable retinitis pigmentosa (RP).
      Biochemical and in vitro studies have demonstrated that many RP-linked mutant
      rhodopsins produce misfolded rhodopsin proteins, which are prone to aggregation
      and retention within the endoplasmic reticulum, where they cause endoplasmic
      reticulum stress and activate the Unfolded Protein Response signaling pathways.
      Many vertebrate models of retinal degeneration have been created through
      expression of RP-linked rhodopsins in photoreceptors including, but not limited
      to, VPP/GHL mice, P23H Rhodopsin frogs, P23H rhodopsin rats, S334ter rhodopsin
      rats, C185R rhodopsin mice, T17M rhodopsin mice, and P23H rhodopsin mice. These
      models have provided many opportunities to test therapeutic strategies to prevent
      retinal degeneration and also enabled in vivo investigation of cellular and
      molecular mechanisms responsible for photoreceptor cell death. Here, we examine
      and compare the contribution of endoplasmic reticulum stress to retinal
      degeneration in several vertebrate models of RP generated through expression of
      mutant rhodopsins. 

PMID- 24664748
TI  - Bisretinoid degradation and the ubiquitin-proteasome system.
AB  - Bisretinoid fluorophores of retinal pigment epithelial (RPE) lipofuscin have been
      shown to undergo degradation in two ways, the first involving photofragmentation
      following photooxidation of their polyene structure and the second being enzyme
      mediated and limited, thus far, to in vitro models employing horseradish
      peroxidase (HRP). Here we show that both of these processes impact the ubiquitin
      proteasome system (UPS) of the RPE cell. By measuring the consumption of A2E and
      all-trans-retinal dimer by HPLC, we confirmed that both HRP-mediated and
      photodegradation of the compounds occurred and that in both cases the
      chymotrypsin-like and trypsin-like activities of the proteasome system were
      decreased. With HRP-mediated degradation of A2E, there was a small negative
      impact on cell viability that was not mitigated by elevating gluthathione in the
      cell.

PMID- 24664749
TI  - Analysis of mouse RPE sheet morphology gives discriminatory categories.
AB  - We are interested in developing quantitative tools to study retinal pigmented
      epithelium (RPE) morphology. We want to detect changes in the RPE by strain,
      disease, genotype, and age. Ultimately these tools should be useful in predicting
      retinal disease progression. The morphometric data will also help us to
      understand RPE sheet formation and barrier functions. A clear disruption of the
      regular cell size and shape appeared in mouse mutants. Aspect ratio and cell area
      together gave rise to principal components that predicted age and genotype
      accurately and well before visually obvious damage could be seen. 

PMID- 24664750
TI  - High glucose activates ChREBP-mediated HIF-1alpha and VEGF expression in human
      RPE cells under normoxia.
AB  - OBJECTIVE: Because retina-damaging angiogenesis is controlled by vascular
      endothelial growth factor (VEGF) and people with higher glucose intakes are more
      susceptible to retinal complications that may be due to increased VEGF, it is
      crucial to elucidate relations between glucose exposure and VEGF expression. We
      aimed to determine if a carbohydrate response element binding protein (ChREBP)
      plays a role in the transcriptional up-regulation of hypoxia-inducible factor
      1alpha (HIF-1alpha) and the downstream VEGF expression in retinal pigment
      epithelial (RPE) cells exposed to high glucose under normoxic conditions.
      METHODS: ARPE19 cells were exposed to 5.6, 11, 17, 25 and 30 mM glucose for 48 h
      in serum-free culture media under normoxic (21 % O2) conditions. Protein and mRNA
      expression of indicated genes were determined by immunoblot analyses and real
      time RT-PCR, respectively. An enzyme-linked immunosorbent assay (ELISA) was used
      to detect the concentrations of VEGF in the media. Immunofluorescence (IF) and
      chromatin immunoprecipitation (ChIP) for ChREBP were used to demonstrate nuclear
      translocation and HIF-1alpha gene promoter association, respectively. RESULTS:
      Immunoblot analyses showed that HIF-1alpha levels were positively related to
      levels of glucose exposure between 5.6-25 mM in the RPE cells, indicating the
      induction and stabilization of HIF-1alpha by elevated glucose under normoxic
      conditions. Human lens epithelial cells and HeLa cells did not respond to high
      glucose, implying that this phenomenon is cell type-specific. Real-time RT-PCR
      for HIF-1alpha and VEGF and ELISA for VEGF indicated that high glucose is
      associated with elevated production of HIF-1alpha-induced VEGF, an established
      inducer of neovascularization, in the RPE cells. IF analyses showed that,
      although ChREBP was expressed under both low (5.6 mM) and high (25 mM) glucose
      conditions, it appeared more in the nuclear region than in the cytosol of the RPE
      cells after the high glucose treatment. ChIP analyses suggested a HIF-1alpha gene
      promoter association with ChREBP under the high glucose condition. These results
      imply that RPE cells use cytosolic ChREBP as a glucose sensor to up-regulate HIF
      1alpha expression. CONCLUSION: These results suggest a high glucose-induced,
      ChREBP-mediated, and normoxic HIF-1alpha activation that may be partially
      responsible for neovascularization in both diabetic and age-related retinopathy.

PMID- 24664751
TI  - Sphingolipids in ocular inflammation.
AB  - Sphingolipids are essential to cell membrane structure and the development and
      maintenance of neural tissues. The role of bioactive sphingolipids has been
      established in numerous cellular events, including cell survival, growth, and
      apoptosis. Ocular inflammatory and autoimmune diseases involve activation and
      migration of endothelial cells, neovascularization, and infiltration of immune
      cells into various tissues. Clinically, the impact and role of sphingolipid
      mediated signaling is increasingly being appreciated in the pathogenesis and
      treatment of diseases ranging from multiple sclerosis to neovascularization in
      age-related macular degeneration and diabetic retinopathy. In this review, we
      discuss our current knowledge and understanding of sphingolipid metabolism and
      signaling associated with the pathogenesis of ocular diseases. 

PMID- 24664752
TI  - Biosynthesis of very long-chain polyunsaturated fatty acids in hepatocytes
      expressing ELOVL4.
AB  - Elongation of Very Long chain fatty acids-4 (ELOVL4) is a fatty acid condensing
      enzyme that mediates biosynthesis of very long chain polyunsaturated fatty acids
      (VLC-PUFA; >= C28) in a limited number of tissues. Depletion of VLC-PUFA in
      retinal photoreceptors leads to retinal dysfunction and likely contributes to
      autosomal dominant Stargardt-like macular dystrophy (STGD3) pathology. In
      addition, depletion of VLC-PUFA in rodent testicular tissues leads to sterility.
      These results suggest that VLC-PUFA synthesized in situ play a unique role that
      cannot be compensated for by other fatty acid species. Though liver is the major
      fatty acid biosynthetic organs, it does not express the ELOVL4 protein; hence, no
      VLC-PUFA are detected in the blood and plasma. Thus, delivery of these VLC-PUFA
      to target tissues to compensate for their reduction caused by disease presents a
      challenge. We hypothesized that expression of ELOVL4 in the liver will result in
      the biosynthesis of VLC-PUFA that could be transported via the bloodstream to
      target tissues such as retina, brain and testis. Hence, we evaluated the ability
      of rat hepatoma (4HIIE) and human hepatocyte (HepG2) cells to synthesize VLC-PUFA
      by expressing ELOVL4 in these cells. We showed that, in the presence of ELOVL4,
      both 4HIIE and HepG2 cells are capable of VLC-PUFA biosynthesis. We propose that
      transgenic expression of ELOVL4 in the liver will result in the biosynthesis of
      VLC-PUFA that can be transported to target. 

PMID- 24664753
TI  - Very long chain polyunsaturated fatty acids and rod cell structure and function.
AB  - The gene encoding Elongation of Very Long Chain Fatty Acids-4 (ELOVL4) is mutated
      in patients with autosomal dominant Stargardt's Macular Dystrophy Type 3 (STDG3).
      ELOVL4 catalyzes the initial condensation step in the elongation of
      polyunsaturated fatty acids (PUFA) containing more than 26 carbons (26C) to very
      long chain PUFA (VLC-PUFA; C28 and greater). To investigate the role of VLC-PUFA
      in rod photoreceptors, we generated mice with rod-specific deletion of Elovl4
      (RcKO). The mosaic deletion of rod-expressed ELOVL4 protein resulted in a 36 %
      lower amount of VLC-PUFA in the retinal phosphatidylcholine (PC) fraction
      compared to retinas from wild-type mice. However, this reduction was not
      sufficient to cause rod dysfunction at 7 months or photoreceptor degeneration at
      9 or 15 months. 

PMID- 24664754
TI  - Oxidative stress regulation by DJ-1 in the retinal pigment epithelium.
AB  - DJ-1 is a protein expressed in many tissues including the brain where it has been
      extensively studied due to its association with Parkinson's Disease (PD). DJ-1
      was reported to function as an antioxidant, redox-sensitive molecular chaperone,
      and transcription regulator, which protected cells from oxidative stress by
      modifying signaling pathways that regulate cell survival. Here we discuss our
      progress toward characterization of the DJ-1 function in the protection of RPE to
      oxidative stress. 

PMID- 24664755
TI  - The role of reactive oxygen species in ocular malignancy.
AB  - Increased production of reactive oxygen species (ROS) is an attribute of
      malignant cells and is linked to the development of many of the characteristics
      considered "hallmarks of cancer (Hanahan and Weinberg, Cell 144(5), 2011, 646
      674)." Among these are sustained proliferative signaling, induction of new
      vascular growth, promotion of invasion, and metastatic potential. Maintaining the
      balance between the beneficial biological functions of ROS and the dysregulation
      seen in human disease such as cancer, presents a daunting conundrum in the future
      of oncology research. ROS involvement is pervasive throughout the process of
      tumorigenesis and subsequent cancer growth, yet the response to both pro- and
      antioxidant based therapy is varied. We will review the ROS species in the
      pathogenesis of primary ocular malignancy with consideration of potential targets
      for therapeutic intervention. 

PMID- 24664757
TI  - Role of endothelial cell and pericyte dysfunction in diabetic retinopathy: review
      of techniques in rodent models.
AB  - Diabetic Retinopathy is one of the hallmark microvascular diseases secondary to
      diabetes. Endothelial cells and pericytes are key players in the pathogenesis.
      Interaction between the two cell types is important in the regulation of vascular
      function and the maintenance of the retinal homeostatic environment. There are
      currently several approaches to analyze changes in morphology and function of the
      two cell types. Morphologic approaches include trypsin digest, while functional
      approaches include studying blood flow. This review explores the advantages and
      limitations of various methods and summarizes recent experimental studies of EC
      and pericyte dysfunction in rodent models of DR. An improved understanding of the
      role played by EC and pericyte dysfunction can lead to enhanced insights into
      retinal vascular regulation in DR and open new avenues for future treatments that
      reverse their dysfunction. 

PMID- 24664756
TI  - The effects of IRE1, ATF6, and PERK signaling on adRP-linked rhodopsins.
AB  - Many mutations in rhodopsin gene linked to retinitis pigmentosa (RP) cause
      rhodopsin misfolding. Rod photoreceptor cells expressing misfolded rhodopsin
      eventually die. Identifying mechanisms to prevent rhodopsin misfolding or to
      remove irreparably misfolded rhodopsin could provide new therapeutic strategies.
      IRE1, ATF6, and PERK signaling pathways, collectively called the unfolded protein
      response (UPR), regulate the functions of endoplasmic reticulum, responsible for
      accurate folding of membrane proteins such as rhodopsin. We used chemical and
      genetic approaches to selectively activate IRE1, ATF6, or PERK signaling pathways
      one at a time and analyzed their effects on mutant rhodopsin linked to RP. We
      found that both artificial IRE1 and ATF6 signaling promoted the degradation of
      mutant rhodopsin with lesser effects on wild-type rhodopsin. Furthermore, IRE1
      and ATF6 signaling preferentially reduced levels of aggregated rhodopsins. By
      contrast, PERK signaling reduced levels of wild-type and mutant rhodopsin. These
      studies indicate that activation of either IRE1, ATF6, or PERK prevents mutant
      rhodopsin from accumulating in the cells. In addition, activation of IRE1 or ATF6
      can selectively remove aggregated or mutant rhodopsin from the cells and may be
      useful in treating RP associated with rhodopsin protein misfolding. 

PMID- 24664758
TI  - Autophagy induction does not protect retina against apoptosis in
      ischemia/reperfusion model.
AB  - The role played by autophagy after ischemia/reperfusion (I/R) in the retina
      remains unknown. Our study investigated whether ischemic injury in the retina,
      which causes an energy crisis, would induce autophagy. Retinal ischemia was
      induced by elevation of the intraocular pressure and modulation of autophagic
      markers was analyzed at the protein levels in an early and late phase of
      recovery. Following retinal ischemia an increase in LC3BII was first observed in
      the early phase of recovery but did not stay until the late phase of recovery.
      Post-ischemic induction of autophagy by intravitreal rapamycin administration did
      not provide protection against the lesion induced by the ischemic stress. On the
      contrary, an increase in the number of apoptotic cells was observed following I/R
      in the rapamycin treated retinas. 

PMID- 24664759
TI  - Advances in AAV vector development for gene therapy in the retina.
AB  - Adeno-associated virus (AAV) is a small, non-pathogenic dependovirus that has
      shown great potential for safe and long-term expression of a genetic payload in
      the retina. AAV has been used to treat a growing number of animal models of
      inherited retinal degeneration, though drawbacks-including a limited carrying
      capacity, slow onset of expression, and a limited ability to transduce some
      retinal cell types from the vitreous-restrict the utility of AAV for treating
      some forms of inherited eye disease. Next generation AAV vectors are being
      created to address these needs, through rational design efforts such as the
      creation of self-complementary AAV vectors for faster onset of expression and
      specific mutations of surface-exposed residues to increase transduction of viral
      particles. Furthermore, directed evolution has been used to create, through an
      iterative process of selection, novel variants of AAV with newly acquired,
      advantageous characteristics. These novel AAV variants have been shown to improve
      the therapeutic potential of AAV vectors, and further improvements may be
      achieved through rational design, directed evolution, or a combination of these
      approaches, leading to broader applicability of AAV and improved treatments for
      inherited retinal degeneration. 

PMID- 24664760
TI  - Cone specific promoter for use in gene therapy of retinal degenerative diseases.
AB  - Achromatopsia (ACHM) is caused by a progressive loss of cone photoreceptors
      leading to color blindness and poor visual acuity. Animal studies and human
      clinical trials have shown that gene replacement therapy with adeno-associate
      virus (AAV) is a viable treatment option for this disease. Although there have
      been successful attempts to optimize capsid proteins for increased specificity,
      it is simpler to restrict expression via the use of cell type-specific promoters.
      To target cone photoreceptors, a chimeric promoter consisting of an enhancer
      element of interphotoreceptor retinoid-binding protein promoter and a minimal
      sequence of the human transducin alpha-subunit promoter (IRBPe/GNAT2) was
      created. Additionally, a synthetic transducin alpha-subunit promoter
      (synGNAT2/GNAT2) containing conserved sequence blocks located downstream of the
      transcriptional start was created. The strength and specificity of these
      promoters were evaluated in murine retina by immunohistochemistry. The results
      showed that the chimeric, (IRBPe/GNAT2) promoter is more efficient and specific
      than the synthetic, synGNAT2/GNAT2 promoter. Additionally, IRBPe/GNAT2-mediated
      expression was found in all cone subtypes and it was improved over existing
      promoters currently used for gene therapy of achromatopsia. 

PMID- 24664761
TI  - Episomal maintenance of S/MAR-containing non-viral vectors for RPE-based
      diseases.
AB  - The efficacy of non-viral genetic therapies has historically been limited by
      transient gene expression and vector loss. Scaffold matrix attachment regions
      (S/MARs) have been shown to augment transcription, promote episomal maintenance,
      and provide insulator-like function to DNA in in vitro and in vivo systems. Here
      we explore the ability of S/MAR elements to mediate these effects in retinal
      pigment epithelial (RPE) cells with the eventual goal of improving the
      persistence of expression of our non-viral gene delivery tools. We engineered an
      RPE-specific reporter vector with or without an S/MAR immediately downstream of
      the eGFP expression cassette. We show that the S/MAR vector is maintained as an
      episome for up to 1 year. Experiments in which rhodamine-labeled DNA was
      delivered to the subretinal space of mice show better persistence of the S/MAR
      containing vector in the RPE than the non-S/MAR vector. These results suggest
      that inclusion of the S/MAR region promotes episomal maintenance of plasmid DNA
      in the RPE after subretinal delivery and that inclusion of this DNA element may
      be beneficial for non-viral ocular gene transfer. 

PMID- 24664762
TI  - Gene therapy in the rd6 mouse model of retinal degeneration.
AB  - The rd6 mouse is a natural model of an RPE-based (retinal pigment epithelium)
      autosomal recessive retinitis pigmentosa (RP) caused by mutations in the Mfrp
      (membrane-type frizzled related protein) gene. Previously, we showed that
      subretinal delivery of the wild-type mouse Mfrp mediated by a tyrosine-capsid
      mutant scAAV8 (Y733F) vector prevented photoreceptor cell death, and rescued
      retinal function as assessed by electroretinography. In this study, we describe
      the effect of gene therapy on the retinal structure and function in rd6 mice
      using a quadruple (Y272, 444, 500, 730F) tyrosine-capsid mutant scAAV2 viral
      vector delivered subretinally at postnatal day 14 (P14). We show that therapy is
      effective at slowing the photoreceptor degeneration, and in preventing the
      characteristic accumulation of abnormal phagocytic cells in the subretinal space.
      MFRP expression as driven by the ubiquitous chicken beta-actin (smCBA) promoter
      in treated rd6 mice was found predominantly in the RPE apical membrane and the
      entire length of its microvilli, as well as in the photoreceptor inner segments,
      suggesting a potential interaction with actin filaments. In spite of preserving
      retinal morphology, the effects of gene therapy on retinal function were minimal,
      suggesting that the scAAV8 (Y733F) vector may be more efficient for the treatment
      of RP caused by Mfrp mutations. 

PMID- 24664763
TI  - Gene therapy for Stargardt disease associated with ABCA4 gene.
AB  - Mutations in the photoreceptor-specific flippase ABCA4 lead to accumulation of
      the toxic bisretinoid A2E, resulting in atrophy of the retinal pigment epithelium
      (RPE) and death of the photoreceptor cells. Many blinding diseases are associated
      with these mutations including Stargardt's disease (STGD1), cone-rod dystrophy,
      retinitis pigmentosa (RP), and increased susceptibility to age-related macular
      degeneration. There are no curative treatments for any of these dsystrophies.
      While the monogenic nature of many of these conditions makes them amenable to
      treatment with gene therapy, the ABCA4 cDNA is 6.8 kb and is thus too large for
      the AAV vectors which have been most successful for other ocular genes. Here we
      review approaches to ABCA4 gene therapy including treatment with novel AAV
      vectors, lentiviral vectors, and non-viral compacted DNA nanoparticles.
      Lentiviral and compacted DNA nanoparticles in particular have a large capacity
      and have been successful in improving disease phenotypes in the Abca4 (-/-)
      murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat
      patients with ABCA4-associated Startgardt's disease (STGD1). As a result of the
      development of these novel technologies, effective therapies for ABCA4-associated
      diseases may finally be within reach. 

PMID- 24664764
TI  - Assessment of different virus-mediated approaches for retinal gene therapy of
      Usher 1B.
AB  - Usher syndrome type 1B, which is characterized by congenital deafness and
      progressive retinal degeneration, is caused by the loss of the function of MYO7A.
      Prevention of the retinal degeneration should be possible by delivering
      functional MYO7A to retinal cells. Although this approach has been used
      successfully in clinical trials for Leber congenital amaurosis (LCA2), it remains
      a challenge for Usher 1B because of the large size of the MYO7A cDNA. Different
      viral vectors have been tested for use in MYO7A gene therapy. Here, we review
      approaches with lentiviruses, which can accommodate larger genes, as well as
      attempts to use adeno-associated virus (AAV), which has a smaller packaging
      capacity. In conclusion, both types of viral vector appear to be effective.
      Despite concerns about the ability of lentiviruses to access the photoreceptor
      cells, a phenotype of the photoreceptors of Myo7a-mutant mice can be corrected.
      And although MYO7A cDNA is significantly larger than the nominal carrying
      capacity of AAV, AAV-MYO7A in single vectors also corrected Myo7a-mutant
      phenotypes in photoreceptor and RPE cells. Interestingly, however, a dual AAV
      vector approach was found to be much less effective. 

PMID- 24664765
TI  - Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse
      model of retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a severe retinal disease characterized by a
      progressive degeneration of rod photoreceptors and a secondary loss of cone
      function. Here, we used CNGB1-deficient (CNGB1(-/-)) mice, a mouse model for
      autosomal recessive RP, to evaluate the efficacy of adeno-associated virus (AAV)
      vector-mediated gene therapy for the treatment of RP. The treatment restored
      normal expression of rod CNG channels and rod-driven light responses in the
      CNGB1(-/-) retina. This led to a substantial delay of retinal degeneration and
      long-term preservation of retinal morphology. Finally, treated CNGB1(-/-) mice
      performed significantly better than untreated mice in a rod-dependent vision
      guided behavior test. In summary, this study holds promise for the treatment of
      rod channelopathy-associated retinitis pigmentosa by AAV-mediated gene
      replacement. 

PMID- 24664766
TI  - Therapy strategies for Usher syndrome Type 1C in the retina.
AB  - The Usher syndrome (USH) is the most common form of inherited deaf-blindness with
      a prevalence of ~ 1/6,000. Three clinical subtypes (USH1-USH3) are defined
      according to the severity of the hearing impairment, the presence or absence of
      vestibular dysfunction and the age of onset of retinitis pigmentosa (RP). USH1 is
      the most severe subtype with congenital severe to profound hearing loss and onset
      of RP before puberty. Currently only the amelioration of the hearing deficiency
      is implemented, but no treatment of the senso-neuronal degeneration in the eye
      exists.In our studies we are focusing on the evaluation of gene-based therapies
      to cure the retinal degeneration of USH1C patients: (i) gene augmentation using
      recombinant adeno-associated virus, (ii) genome editing by homologous
      recombination mediated by zinc-finger nucleases and, (iii) read-through therapy
      using novel designer aminoglycosides and PTC124. Latter compounds target in-frame
      nonsense mutations which account for ~ 20 % of all USH cases.All analyzed gene
      based therapy strategies lead to the restoration of USH protein expression. These
      adjustments may be sufficient to reduce the progression of retinal degeneration,
      which would greatly improve the life quality of USH patients. 

PMID- 24664767
TI  - Nipradilol promotes axon regeneration through S-nitrosylation of PTEN in retinal
      ganglion cells.
AB  - Nipradilol (Nip) is registered as an anti-glaucoma agent. More recently, a
      protective effect of Nip has been demonstrated in retinal ganglion cells (RGCs)
      mediated by S-nitrosylation of antioxidative-related Keap1 protein due to its
      nitric oxide (NO)-donating effect. It also has been reported that Nip promoted
      axon outgrowth in cat RGCs. However, the detailed mechanism remains unclear. NO
      physiologically regulates numerous cellular responses through S-nitrosylation of
      protein at cysteine residues. It has been reported that phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) deletion strongly showed axon
      regeneration after optic nerve injury. PTEN inactivation by S-nitrosylation
      results in the accumulation of phosphatidylinositol (3, 4, 5) triphosphate (PIP3)
      and the activation of Akt/mammalian target of rapamycin (mTOR) signaling. The
      ribosomal S6 kinase 1 (S6K) which can monitor as phospho-S6 (pS6) is one of major
      target of mTOR. In this study, we investigated the possibility that Nip can
      promote axon outgrowth in RGCs by Akt/mTOR signaling thorough S-nitrosylation of
      PTEN. 

PMID- 24664768
TI  - Reciprocal changes in factor XIII and retinal transglutaminase expressions in the
      fish retina during optic nerve regeneration.
AB  - Unlike mammals, fish retinal ganglion cells have the capacity to repair their
      axons even after optic nerve transection. In the process of fish optic nerve
      regeneration, a large number of genes have been described as regeneration
      associated molecules. Using molecular cloning techniques, we identified two types
      of cDNA clones belonging to the transglutaminase (TG) family which were
      upregulation genes; one is cellular factor XIII (cFXIII) and the other is a
      tissue type TG named retinal transglutaminase (TGR). cFXIII mRNA started to
      increase in the retinal ganglion cells at 1-2 days, peaked at 5-7 days, and
      returned to the control level by 20 days post optic nerve injury. In contrast,
      TGR mRNA started to increase at day 5-10, peaked at day 20, and then gradually
      decreased by day 40 after nerve injury. To elucidate the molecular involvement of
      these TGs in optic nerve regeneration, we studied the effects of recombinant TGR
      protein or overexpression of cFXIII using a retinal explant culture system.
      cFXIII effectively induced neurite outgrowth only from naive (intact) retinas. In
      contrast, the TGR protein significantly enhanced neurite outgrowth only from
      primed retinas, in which the optic nerve had been crushed 5-7 days previously.
      These reciprocal expressions of cFXIII and TGR suggest that these two types of
      TGs are important for the neurite sprouting and axonal elongation processes,
      respectively, during optic nerve regeneration processes. 

PMID- 24664769
TI  - N-acetylserotonin: circadian activation of the BDNF receptor and neuroprotection
      in the retina and brain.
AB  - TrkB is the cognate receptor for brain-derived neurotrophic factor (BDNF), a
      member of the neurotrophin family involved in neuronal survival, neurogenesis and
      synaptic plasticity. BDNF has been shown to protect photoreceptors from light
      induced retinal degeneration (LIRD) and to improve ganglion cell survival
      following optic nerve damage. However, the utility of BDNF as a retinal
      neuroprotectant is limited by its short half-life, inability to cross the blood
      brain and blood-retinal barriers, and activation of the proapoptotic p75
      neurotrophin receptor. N-Acetylserotonin (NAS) is a naturally occurring chemical
      intermediate in the melatonin biosynthetic pathway in the pineal gland and
      retina. Its synthesis occurs in a circadian fashion with high levels at night and
      is suppressed by light exposure. Until recently, NAS was thought to function
      primarily as a melatonin precursor with little or no biological function of its
      own. We have now shown that TrkB activation in the retina and hippocampus is
      circadian in C3H/f(+/+) mice, which synthesize NAS, but not in C57BL/6 mice,
      which have a mutation in the gene encoding the enzyme that converts serotonin to
      NAS. In addition, treatment of mice exogenous NAS, but not with serotonin or
      melatonin, activates TrkB during the daytime in a BDNF-independent manner. NAS
      appears to have neuroprotective properties and its administration reduces caspase
      3 activation in the brain in response to kainic acid, a neurotoxic glutamate
      analog. We have developed structural analogs of NAS that activate TrkB. One of
      these derivatives, N- [2-(-indol-3-yl)ethyl]-2-oxopiperideine-3-carboximide
      (HIOC), selectively activates TrkB with greater potency than NAS and has a
      significantly 5-hydroxy-1Hlonger biological half-life than NAS after systemic
      administration. HIOC administration results in long-lasting activation of TrkB
      and downstream signaling kinases. The compound can pass the blood-brain and blood
      retinal barriers when administered systemically and reduces kainic acid-induced
      neuronal cell death in a TrkB-dependent manner. Systemic administration of HIOC
      mitigates LIRD, assessed electrophysiologically and morphometrically. Hence, NAS
      may function as an endogenous circadian neurotrophin-like compound and HIOC is a
      good lead compound for further drug development for treatment of retinal
      degenerative diseases. 

PMID- 24664771
TI  - Antioxidant therapy for retinal disease.
AB  - Disease mechanisms associated with retinal disease are of immense complexity,
      mutations within 45 genes having been implicated, for example, in retinitis
      pigmentosa, while interplay between genetic, environmental, and demographic
      factors can lead to diabetic retinopathy, age-related macular degeneration, and
      glaucoma. In light of such diversity, any therapeutic modality that can be
      targeted to an early molecular process instrumental in multiple forms of disease,
      such as oxidative stress, holds much attraction. Here, we provide a brief
      overview of a selection of compounds displaying antioxidant activity, which have
      been shown to slow down degeneration of retinal tissues and highlight suggested
      modes of action. 

PMID- 24664770
TI  - A high content screening approach to identify molecules neuroprotective for
      photoreceptor cells.
AB  - PURPOSE: Retinal degenerations are a heterogeneous group of diseases in which
      there is slow but progressive loss of photoreceptors (PR). There are currently no
      approved therapies for treating retinal degenerations. In an effort to identify
      novel small molecules that are (1) neuroprotective and (2) promote PR
      differentiation, we have developed microscale (1,536 well) cell culture assays
      using primary retinal neurons. METHODS: Primary murine retinal cells are
      isolated, seeded, treated with a 1,280 compound chemical library in a 7 point
      titration and then cultured under conditions developed to assay protection
      against an introduced stress or enhance PR differentiation. In the protection
      assays a chemical insult is introduced and viability assessed after 72 h using
      CellTiterGlo, a single-step chemiluminescent reagent. In the differentiation
      assay, cells are isolated from the rhodopsin-GFP knock-in mouse and PR
      differentiation is assessed by fixing cells after 21 days in culture and imaging
      with the Acumen plate-based laser cytometer (TTP Labtech) to determine number and
      intensity of GFP-expressing cells. Positive wells are re-imaged at higher
      resolution with an INCell2000 automated microscope (GE). Concentration-response
      curves are generated to pharmacologically profile each compound and hits
      identified by xx. RESULTS: We have developed PR differentiation and
      neuroprotection assays with a signal to background (S/B) ratios of 11 and 3, and
      a coefficient of variation (CV) of 20 and 9 %, suitable for chemical screening.
      Staurosporine has been shown in our differentiation assay to simultaneously
      increase the number of rhodopsin positive objects while decreasing the mean
      rhodopsin intensity and punctate rhodopsin fluorescent objects. CONCLUSIONS:
      Using primary murine retinal cells, we developed high throughput assays to
      identify small molecules that influence PR development and survival. By screening
      multiple compound concentrations, dose-response curves can be generated, and the
      false negative rate minimized. It is hoped that this work will identify both
      potential preclinical candidates as well as molecular probes that will be useful
      for analysis of the molecular mechanisms that promote PR differentiation and
      survival.

PMID- 24664772
TI  - Pathophysilogical mechanism and treatment strategies for Leber congenital
      amaurosis.
AB  - Mutations in retinoid isomerase, RPE65, or lecithin-retinol acyltransferase
      (LRAT) disrupt 11-cis-retinal recycling and cause Leber congenital amaurosis
      (LCA), the most severe retinal dystrophy in early childhood. We used Lrat (-/-),
      a murine model for LCA, to investigate the mechanism of rapid cone degeneration.
      We found that mislocalized M-opsin was degraded whereas mislocalized S-opsin
      accumulated in Lrat (-/-) cones before the onset of massive ventral/central cone
      degeneration. Since the ventral and central retina expresses higher levels of S
      opsin than the dorsal retina in mice, our results may explain why ventral and
      central cones degenerate more rapidly than dorsal cones in Rpe65 (-/-) and Lrat (
      /-) LCA models. In addition, human blue opsin and mouse S-opsin, but not mouse M
      opsin or human red/green opsins, aggregated to form cytoplasmic inclusions in
      transfected cells, which may explain why blue cone function is lost earlier than
      red/green-cone function in LCA patients. The aggregation of short-wavelength
      opsins likely caused rapid cone degenerations through an ER stress pathway as
      demonstrated in both the Lrat (-/-) retina and transfected cells. Based on this
      mechanism, we designed a new therapy of LCA by reducing ER stress. We found that
      systemic injection of an ER chemical chaperone, tauroursodeoxycholic acid
      (TUDCA), is effective in reducing ER stress, preventing apoptosis, and preserving
      cones in Lrat (-/-) mice. 

PMID- 24664773
TI  - Current and emerging therapies for ocular neovascularisation.
AB  - Ocular neovascularisation (ONV) is a pathological feature of many human blinding
      diseases. Here, we review current pharmacological therapies for these disorders
      and highlight emerging therapies in clinical trial for ONV. Finally, we discuss
      desirable characteristics of future ONV therapies, including innovative
      strategies for novel delivery to the back of the eye. 

PMID- 24664774
TI  - Targeting the PI3K/Akt/mTOR pathway in ocular neovascularization.
AB  - Ocular neovascularization, a common pathological feature of wet age-related
      macular degeneration (AMD), proliferative and diabetic retinopathy (PDR) leads to
      fluid and blood leakage, scar formation and ultimately blindness. Elucidation of
      vascular endothelial growth factor (VEGF) as a key mediator of angiogenesis led
      to clinically approved anti-VEGF agents. However, these drugs are associated with
      adverse side-effects, high costs and extensive clinical burden. The
      phosphatidylinositol-3-kinase (PI3K) pathway is an alternative therapeutic target
      in angiogenic diseases. The PI3K/Akt/mTOR pathway orchestrates an array of normal
      cellular processes, including growth, survival and angiogenesis. Here, we review
      the potential of targeting the PI3K pathway, to treat ocular neovascularization. 

PMID- 24664775
TI  - Pigment epithelium-derived factor protects cone photoreceptor-derived 661W cells
      from light damage through Akt activation.
AB  - Pigment epithelium-derived factor (PEDF) can delay and prevent the death of
      photoreceptors in vivo. We investigated the survival activity of PEDF on cone
      photoreceptor-derived 661W cells in culture, the presence of PEDF receptor (PEDF
      R) in these cells and the activation of prosurvival Akt. Cell death was induced
      by light exposure in the presence of 9-cis retinal. Cell viability assays showed
      that PEDF increased the number of 661W cells exposed to these conditions. Western
      blots showed that PEDF-treated 661W cells had a higher ratio of phosphorylated
      Akt to total Akt than untreated cells. The PEDF receptor PEDF-R was
      immunodetected in the plasma membrane fractions of 661W cells. The results
      demonstrated that PEDF can protect 661W cells against light-induced cell death
      and suggest that the binding of PEDF to cell surface PEDF-R triggers a
      prosurvival signaling pathway. 

PMID- 24664776
TI  - Nanoceria as bona fide catalytic antioxidants in medicine: what we know and what
      we want to know....
AB  - Cerium oxide (CeO2) nanoparticles, CeNPs or nanoceria are inorganic and possess
      catalytic antioxidant activity. They scavenge reactive oxygen species and act as
      an oxygen buffer. Their application in industry is well-established. However,
      their usage as bona fide antioxidants in biological systems has been recent and
      is quite revolutionary. Other reviews have documented nanoceria's protective
      effect in reducing oxidative stress in cell culture and in animal disease models
      that are associated with oxidative stress. We specifically have targeted CeNPs as
      ophthalmic therapeutics to slow the progression of retinal degeneration and as
      anti-angiogenic agents in rodent models. The radical scavenging activity of CeNPs
      is mainly due to the dramatic increase of surface area to volume ratio in these
      nanocrystalline structures. The parameters for CeNPs usage in industrial settings
      are decidedly not suitable for biological applications. In this short review, we
      report the pharmacokinetics, biodistribution, and toxicity evaluation of CeNPs
      when applied as ophthalmic therapeutic agents in an in vivo system. We highlight
      studies that examine how CeNPs behave in biological environments and how they
      interact with bio-macromolecules. We also discuss studies that examine the
      dynamic changes of the surface chemistry of CeNPs in physiological buffers.
      Finally, we raise a list of questions that we think ought to be answered for
      CeNPs to be considered the antioxidants of choice in medicine, specifically in
      the treatment of ocular diseases. 

PMID- 24664777
TI  - Nanoceria and thioredoxin regulate a common antioxidative gene network in tubby
      mice.
AB  - Oxidative stress is a node common to the causes and effects of various ocular
      diseases. We have shown that thioredoxin has neuroprotective effects on tubby
      photoreceptors. We also demonstrated that nanoceria (cerium oxide nanoparticles),
      which are direct antioxidants, have long-term effects on prevention of retinal
      degeneration in tubby mice. Here, using commercially available PCR array plates,
      we surveyed the regulation in expression of 89 oxidative stress-associated genes
      in the eyes of P12 tubby mice which are either intravitreally injected with
      nanoceria or in which the Trx gene is overexpressed. Our data demonstrate that
      nanoceria and Trx regulate the same group of genes associated with antioxidative
      stress and antioxidant defense. 

PMID- 24664778
TI  - Intrascleral transplantation of a collagen sheet with cultured brain-derived
      neurotrophic factor expressing cells partially rescues the retina from damage due
      to acute high intraocular pressure.
AB  - We constructed brain-derived neurotrophic factor (BDNF) expressing rat retinal
      pigment epithelial (RPE) cells by stable transfection of BDNF cDNA, and the RPE
      cells were cultured on a cross-linked collagen sheet (Coll-RPE-BDNF). BDNF
      expression of the Coll-RPE-BDNF was confirmed by western blot, and the Coll-RPE
      BDNF was transplanted into the rabbit sclera. In vivo BDNF expression was
      confirmed by His expression that was linked to the expressing BDNF. The effect of
      the released BDNF was examined in a rabbit acute high intraocular pressure system
      by electroretinogram and histological examination. Statistically significant
      preservation of ERG b wave amplitude was observed in the rabbits treated by Coll
      RPE-BDNF when compared to that of no treatment. Statistically significant
      preservation of the thickness of the inner nuclear layer at the transplanted area
      was observed in the rabbits treated by Coll-RPE-BDNF compared to that of no
      treatment. Intra-scleral Coll-RPE-BDNF transplantation may partially rescue
      retinal cells from acute high intraocular pressure. 

PMID- 24664779
TI  - Neuroprotective effects of low level electrical stimulation therapy on retinal
      degeneration.
AB  - Low-level electrical stimulation applied to the eye has been shown to have
      neuroprotective effects on photoreceptors and retinal ganglion cells. In this
      review, we compare the effects of Subretinal Electrical Stimulation (SES),
      Transcorneal Electrical Stimulation (TES), and Whole Eye Stimulation (WES) on
      preserving retinal structure and function, and visual acuity, in retinal
      degeneration. Similarities and differences in stimulus parameters, targeted cells
      and growth factor expression will be discussed with emphasis on studies that have
      translated laboratory findings into clinical trials. 

PMID- 24664780
TI  - What does three years of hunting great cormorants, Phalacrocorax carbo, tell us?
      Shooting autumn-staging birds as a means of reducing numbers locally.
AB  - BACKGROUND: The population of great cormorants, Phalacrocorax carbo, has
      increased markedly in Europe in the last 30 years, creating conflicts primarily
      with fisheries' interests. Some advocate that there should be a reduction in bird
      numbers on anything from local to regional and pan-European levels. The effect of
      attempts to reduce cormorant numbers by shooting to kill and by shooting to
      reinforce the scaring of birds in two Danish fjords was studied. RESULTS: A total
      of 308, 364 and 459 cormorants were shot in the two fjords during each of three
      annual hunting seasons. When shooting was intensive over a series of days near
      the birds' main roosting and sleeping place, numbers dropped significantly
      compared with non-shooting years. No significant scaring effect was detected when
      shooting was carried out only at random along the shores of the fjords. None of
      the shooting treatments had an effect on the number of cormorants occurring in
      subsequent years. CONCLUSION: These results indicate that large efforts can be
      invested in shooting to scare and kill cormorants without reaching any desired
      reduction in numbers, in particular when the shooting is not coordinated in time
      and space and not undertaken at key roosting sites.

PMID- 24664781
TI  - Berberine reduces ischemia/reperfusion-induced myocardial apoptosis via
      activating AMPK and PI3K-Akt signaling in diabetic rats.
AB  - Diabetes increases the risk of cardiovascular diseases. Berberine (BBR), an
      isoquinoline alkaloid used in Chinese medicine, exerts anti-diabetic effect by
      lowering blood glucose and regulating lipid metabolism. It has been reported that
      BBR decreases mortality in patients with chronic congestive heart failure.
      However, the molecular mechanisms of these beneficial effects are incompletely
      understood. In the present study, we sought to determine whether BBR exerts
      cardioprotective effect against ischemia/reperfusion (I/R) injury in diabetic
      rats and the underlying mechanisms. Male Sprague-Dawley rats were injected with
      low dose streptozotocin and fed with a high-fat diet for 12 weeks to induce
      diabetes. The diabetic rats were intragastrically administered with saline or BBR
      (100, 200 and 400 mg/kg/d) starting from week 9 to 12. At the end of week 12, all
      rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion. BBR
      significantly improved the recovery of cardiac systolic/diastolic function and
      reduced myocardial apoptosis in diabetic rats subjected to myocardial I/R.
      Furthermore, in cultured neonatal rat cardiomyocytes, BBR (50 MUmol/L) reduced
      hypoxia/reoxygenation-induced myocardial apoptosis, increased Bcl-2/Bax ratio and
      decreased caspase-3 expression, together with enhanced activation of PI3K-Akt and
      increased adenosine monophosphate-activated protein kinase (AMPK) and eNOS
      phosphorylation. Pretreatment with either PI3K/Akt inhibitor wortmannin or AMPK
      inhibitor Compound C blunted the anti-apoptotic effect of BBR. Our findings
      demonstrate that BBR exerts anti-apoptotic effect and improves cardiac functional
      recovery following myocardial I/R via activating AMPK and PI3K-Akt-eNOS signaling
      in diabetic rats.

PMID- 24664785
TI  - Household air quality risk factors associated with childhood pneumonia in urban
      Dhaka, Bangladesh.
AB  - To inform interventions to reduce the high burden of pneumonia in urban settings
      such as Kamalapur, Bangladesh, we evaluated household air quality risk factors
      for radiographically confirmed pneumonia in children. In 2009-2010, we recruited
      children < 5 years of age with pneumonia and controls from a population-based
      surveillance for respiratory and febrile illnesses. Piped natural gas was used by
      85% of 331 case and 91% of 663 control households. Crowding, a tin roof in the
      living space, low socioeconomic status, and male sex of the child were risk
      factors for pneumonia. The living space in case households was 28% less likely
      than in control households to be cross-ventilated. Particulate matter
      concentrations were not significantly associated with pneumonia. With increasing
      urbanization and supply of improved cooking fuels to urban areas, the high burden
      of respiratory illnesses in urban populations such as Kamalapur may be reduced by
      decreasing crowding and improving ventilation in living spaces.

PMID- 24664784
TI  - Household water treatment uptake during a public health response to a large
      typhoid fever outbreak in Harare, Zimbabwe.
AB  - Locally manufactured sodium hypochlorite (chlorine) solution has been sold in
      Zimbabwe since 2010. During October 1, 2011-April 30, 2012, 4,181 suspected and
      52 confirmed cases of typhoid fever were identified in Harare. In response to
      this outbreak, chlorine tablets were distributed. To evaluate household water
      treatment uptake, we conducted a survey and water quality testing in 458 randomly
      selected households in two suburbs most affected by the outbreak. Although 75% of
      households were aware of chlorine solution and 85% received chlorine tablets,
      only 18% had reportedly treated stored water and had the recommended protective
      level of free chlorine residuals. Water treatment was more common among
      households that reported water treatment before the outbreak, and those that
      received free tablets during the outbreak (P < 0.01), but was not associated with
      chlorine solution awareness or use before the outbreak (P > 0.05). Outbreak
      response did not build on pre-existing prevention programs.

PMID- 24664787
TI  - Diazonium salts as grafting agents and efficient radical-hydrosilylation
      initiators for freestanding photoluminescent silicon nanocrystals.
AB  - The reactivity of diazonium salts towards freestanding, photoluminescent silicon
      nanocrystals (SiNCs) is reported. It was found that SiNCs can be functionalized
      with aryl groups by direct reductive grafting of the diazonium salts.
      Furthermore, diazonium salts are efficient radical initiators for SiNC
      hydrosilylation. For this purpose, novel electron-deficient diazonium salts,
      highly soluble in nonpolar solvents were synthesized. The SiNCs were
      functionalized with a variety of alkenes and alkynes at room temperature with
      short reaction times. 

PMID- 24664786
TI  - Topical microbicides and HIV prevention in the female genital tract.
AB  - Worldwide, HIV disproportionately affects women who are often unable to negotiate
      traditional HIV preventive strategies such as condoms. In the absence of an
      effective vaccine or cure, chemoprophylaxis may be a valuable self-initiated
      alternative. Topical microbicides have been investigated as one such option. The
      first generation topical microbicides were non-specific, broad-spectrum
      antimicrobial agents, including surfactants, polyanions, and acid buffering gels,
      that generally exhibited contraceptive properties. After extensive clinical
      study, none prevented HIV infection, and their development was abandoned. Second
      generation topical microbicides include agents with selective mechanisms of
      antiviral activity. Most are currently being used for, or have previously been
      explored as, drugs for treatment of HIV. The most advanced of these is tenofovir
      1% gel: the first topical agent shown to significantly reduce HIV infection by
      39% compared to placebo. This review summarizes the evolution of topical
      microbicides for HIV chemoprophylaxis, highlights important concepts learned, and
      offers current and future considerations for this area of research. 

PMID- 24664788
TI  - Somatosensory and vasomotor manifestations of individual and combined stimulation
      of TRPM8 and TRPA1 using topical L-menthol and trans-cinnamaldehyde in healthy
      volunteers.
AB  - BACKGROUND: Activation of TRPM8 and TRPA1 receptors generates cold and cold pain
      sensations, respectively, and is presumably important in clinical pain
      manifestations, such as cold hyperalgesia. This study investigated the
      interaction between TRPM8 and TRPA1 receptors through stimulation of glabrous
      human skin (volar forearm) by topical administration of 40% L-menthol and 10%
      trans-cinnamaldehyde (CA), individually and in combination. METHODS: Sensory
      manifestations were assessed in 10 healthy volunteers via a platform of 11
      quantitative sensory (thermal and mechanical stimuli) and vasomotor tests (skin
      temperature, perfusion and axon-reflex-flare) in a double-blinded randomized
      crossover design. RESULTS: Cold pain threshold was increased (p < 0.01, cold
      allodynia) by L-menthol alone and L-menthol + CA in combination but unaffected by
      CA. Mechanical pain threshold was significantly decreased (mechanical
      hyperalgesia) by all three substances (p < 0.01), with a significant intergroup
      difference found between CA alone and the less decreased L-menthol + CA (p <
      0.05). Application of CA alone and L-menthol + CA in combination showed an
      increase in skin temperature and perfusion significantly larger than that induced
      by L-menthol alone (p < 0.05). An axon-reflex-flare was present after CA
      administration, but was significantly reduced upon addition of L-menthol (p <
      0.01). CONCLUSION: This study elucidates the potential of L-menthol as a counter
      irritant to secondary neurogenic inflammation and provides evidence of an
      intricate interplay between cold receptors TRPA1 and TRPM8, warranting further
      investigation of the neural coding of cold pain perception.

PMID- 24664789
TI  - Development of a sequential multicolor-FISH approach with 13 chromosome-specific
      painting probes for the rapid identification of river buffalo (Bubalus bubalis,
      2n = 50) chromosomes.
AB  - The development of new molecular techniques (array CGH, M-FISH, SKY-FISH, etc.)
      has led to great advancements in the entire field of molecular cytogenetics.
      However, the application of these methods is still very limited in farm animals.
      In the present study, we report, for the first time, the production of 13 river
      buffalo (Bubalus bubalis, 2n = 50) chromosome-specific painting probes, generated
      via chromosome microdissection and the DOP-PCR procedure. A sequential multicolor
      FISH approach is also proposed on the same slide for the rapid identification of
      river buffalo chromosome/arms, namely, 1p-1q, 2p-2q, 3p-3q, 4p-4q, 5p-5q, 18, X,
      and Y, using both conventional and late-replicating banded chromosome
      preparations counterstained by DAPI. The provided 'bank' of chromosome-specific
      painting probes is useful for any further cytogenetic investigation not only for
      the buffalo breeds, but also for other species of the family Bovidae, such as
      cattle, sheep, and goats, for chromosome abnormality diagnosis, and, more
      generally, for evolutionary studies. 

PMID- 24664790
TI  - Nitrogen-doped holey graphitic carbon from 2D covalent organic polymers for
      oxygen reduction.
AB  - Using covalent organic polymer pre-cursors, we have developed a new strategy for
      location control of N-dopant heteroatoms in the graphitic porous carbon, which
      otherwise is impossible to achieve with conventional N-doping techniques. The
      electrocatalytic activities of the N-doped holey graphene analogues are well
      correlated to the N-locations, showing possibility for tailoring the structure
      and property of N-doped carbon nanomaterials. 

PMID- 24664791
TI  - A prospective feasibility study of primary prophylaxis against invasive fungal
      disease with voriconazole following umbilical cord blood transplantation with
      fludarabine-based conditioning.
AB  - Despite the recent introduction of a new class of anti-Aspergillus agents, no
      standard regimen for the prevention of invasive fungal disease (IFD) following
      allogeneic hematopoietic stem cell transplantation has been shown to be superior
      to fluconazole. The present prospective, single-arm study investigated the
      feasibility of voriconazole (VOR) administration as primary prophylaxis in 52
      recipients of umbilical cord blood transplantation (CBT) with fludarabine-based
      conditioning, who had no previous IFD episodes. Proven or probable IFD was
      determined using the European Organization for Research and Treatment of
      Cancer/Invasive Fungal Infections Cooperative Group, and the National Institute
      of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria were
      considered as breakthrough infections. VOR was administered as prophylaxis for a
      total of 6884 patient-days following CBT. The mean duration of VOR administration
      after transplantation was 132 days (range, 1-769); 44 patients (85 %) had
      advanced disease, 15 (29 %) had a history of allogeneic HSCT, and 29 (56 %)
      received systemic corticosteroid therapy for allogeneic immune-mediated
      complications. Under the prophylaxis with VOR, one patient developed probable
      invasive aspergillosis on day 71, and the cumulative incidence of IFD was 4.5 %
      at day 180. None of the patients developed breakthrough candida or zygomycetes
      infections. Under the extensive therapeutic dose monitoring, VOR was safely
      administered with a calcineurin inhibitor and was well tolerated. These results
      suggest that VOR represents a feasible primary prophylactic agent for IFD after
      CBT with fludarabine-based conditioning.

PMID- 24664792
TI  - Long-term use of valproic acid in US veterans is associated with a reduced risk
      of smoking-related cases of head and neck cancer.
AB  - BACKGROUND: Epigenetic events play a major role in the carcinogenesis of tobacco
      related cancers. The authors conducted a retrospective cohort study to evaluate
      the effects of exposure to the anticonvulsant agent valproic acid (VPA), a
      histone deacetylase inhibitor, on the risk of developing cancers of the lung,
      head and neck, prostate, bladder, and colon. METHODS: The study was based on the
      2002 through 2008 National Veterans Affairs (VA) medical SAS data set linked to
      the VA Central Cancer Registry. The cohort was defined as subjects aged>40 years
      who were followed in the VA system for at least 1 year for 1 of 4 diagnoses for
      which a VPA indication exists (bipolar disorder, posttraumatic stress disorder,
      migraines, and seizures). Multivariable Cox proportional hazards models were used
      to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) reflecting
      the association between use of VPA and cancer incidence. RESULTS: VPA use was
      associated with a significant reduction in the risk of cancers of the head and
      neck (HR, 0.66; 95% CI, 0.48-0.92). Additional associations were noted with the
      duration of treatment and median VPA drug levels. No significant differences in
      cancer incidence were observed for cancers of the lung (HR, 1.00; 95% CI, 0.84
      1.19), bladder (HR, 0.86; 95% CI, 0.64-1.15), colon (HR, 0.95; 95% CI, 0.74
      1.22), and prostate (HR, 0.96; 95% CI, 0.88-1.12). CONCLUSIONS: Use of VPA is
      associated with a lower risk of developing head and neck cancers.

PMID- 24664794
TI  - Total hip replacement due to primary osteoarthritis in relation to cumulative
      occupational exposures and lifestyle factors: a nationwide nested case-control
      study.
AB  - OBJECTIVE: To investigate the risk of total hip replacement (THR) due to primary
      osteoarthritis in relation to cumulative occupational mechanical exposures and
      lifestyle factors. METHODS: Using register information, we identified first-time
      THR cases within the Danish working population in 2005-2006. For each case, 2 age
      and sex-matched controls were drawn. Persons within 2,500 randomly selected case
      control sets received a questionnaire about job history, weight at age 25 years,
      present weight and height, smoking, and sports activities at age 25 years. The
      job history was combined with a job exposure matrix. Cumulative exposure
      estimates were expressed according to the pack-year concept of smoking (e.g.,
      cumulative lifting was expressed as ton-years). We used conditional logistic
      regression for statistical analyses. RESULTS: In total, 1,776 case-control sets
      (71%) were available for analysis. The adjusted odds ratio (OR) for exposure to
      >=20 ton-years was 1.35 (95% confidence interval [95% CI] 1.05-1.74) for men and
      1.00 (95% CI 0.73-1.41) for women. Standing/walking and whole body vibration
      showed no associations. The adjusted OR for body mass index (BMI) >=30 kg/m(2) at
      age 25 years was 2.44 (95% CI 1.38-4.32) for men and 5.12 (95% CI 2.30-11.39) for
      women. The corresponding adjusted ORs for an increase in BMI of >=10 kg/m(2)
      since age 25 years were 2.16 (95% CI 1.25-3.70) and 2.46 (95% CI 1.47-4.13).
      Sports participation showed weak positive associations, while pack-years of
      smoking showed no associations. CONCLUSION: The results indicated a modest
      increase in risk of THR in relation to cumulative lifting among men and an
      increased risk in relation to a high BMI at age 25 years and to a gain in BMI in
      both sexes.

PMID- 24664793
TI  - Validation of a claims-based antipsychotic polypharmacy measure.
AB  - Purpose Given the metabolic and neurologic side effects of antipsychotics and
      concerns about the increased risks associated with concomitant use, antipsychotic
      polypharmacy is a quality concern. This study assessed the operating
      characteristics of a Medicaid claims-based measure of antipsychotic polypharmacy.
      Methods A random sample from 10 public mental health clinics and 312 patients met
      criteria for this study. Medical record extractors were blind to measure status.
      We examined the prevalence, sensitivity, specificity, and positive predictive
      value (PPV) in Medicaid claims, testing nine different definitions of
      antipsychotic polypharmacy, including >14, >60, or >90 days concurrent use of >=2
      antipsychotic agents, each with allowable gaps of up to 0, 14, or 32 days in
      days' supply of antipsychotic medications. Results All Medicaid claims measure
      definitions tested had excellent specificity and PPV (>91%). Good to excellent
      sensitivity was dependent upon use of a 32-day gap allowance, particularly as
      duration of concurrent antipsychotic use increased. The proposed claims-based
      measure (90-day concurrent use of >=2 or more antipsychotics, allowing for a 32
      day gap) had excellent specificity (99.1%, 95%CI: 98.2-99.6) and PPV (90.9%,
      95%CI: 83.1-95.7) with good sensitivity (79.4%, 95%CI: 70.4-86.6). The overall
      level of concordance between claims and medical record-based categorization of
      antipsychotic polypharmacy was high (96.4%, n = 301/312 clients, Cohen's K =
      84.7, 95%CI: 75.9-93.5). Discrepant cases were reviewed, and implications are
      discussed. Conclusions Administrative claims data can be used to construct valid
      measures of antipsychotic polypharmacy.

PMID- 24664795
TI  - The role of screening and treatment in the transmission dynamics of HIV/AIDS and
      tuberculosis co-infection: a mathematical study.
AB  - In this paper, we present a deterministic non-linear mathematical model for the
      transmission dynamics of HIV and TB co-infection and analyze it in the presence
      of screening and treatment. The equilibria of the model are computed and
      stability of these equilibria is discussed. The basic reproduction numbers
      corresponding to both HIV and TB are found and we show that the disease-free
      equilibrium is stable only when the basic reproduction numbers for both the
      diseases are less than one. When both the reproduction numbers are greater than
      one, the co-infection equilibrium point may exist. The co-infection equilibrium
      is found to be locally stable whenever it exists. The TB-only and HIV-only
      equilibria are locally asymptotically stable under some restriction on
      parameters. We present numerical simulation results to support the analytical
      findings. We observe that screening with proper counseling of HIV infectives
      results in a significant reduction of the number of individuals progressing to
      HIV. Additionally, the screening of TB reduces the infection prevalence of TB
      disease. The results reported in this paper clearly indicate that proper
      screening and counseling can check the spread of HIV and TB diseases and
      effective control strategies can be formulated around 'screening with proper
      counseling'.

PMID- 24664796
TI  - Dynamics of lysozyme and its hydration water under an electric field.
AB  - The effects of a static electric field on the dynamics of lysozyme and its
      hydration water are investigated by means of incoherent quasi-elastic neutron
      scattering (QENS). Measurements were performed on lysozyme samples, hydrated
      respectively with heavy water (D2O) to capture the protein dynamics and with
      light water (H2O), to probe the dynamics of the hydration shell, in the
      temperature range from 210 < T < 260 K. The hydration fraction in both cases was
      about ~ 0.38 gram of water per gram of dry protein. The field strengths
      investigated were respectively 0 kV/mm and 2 kV/mm (~2 * 10(6) V/m) for the
      protein hydrated with D2O and 0 kV and 1 kV/mm for the H2O-hydrated counterpart.
      While the overall internal protons dynamics of the protein appears to be
      unaffected by the application of an electric field up to 2 kV/mm, likely due to
      the stronger intra-molecular interactions, there is also no appreciable
      quantitative enhancement of the diffusive dynamics of the hydration water, as
      would be anticipated based on our recent observations in water confined in silica
      pores under field values of 2.5 kV/mm. This may be due to the difference in
      surface interactions between water and the two adsorption hosts (silica and
      protein), or to the existence of a critical threshold field value Ec ~2-3 kV/mm
      for increased molecular diffusion, for which electrical breakdown is a limitation
      for our sample.

PMID- 24664797
TI  - Review of innovations in digital health technology to promote weight control.
AB  - Advances in technology have contributed to the obesity epidemic and worsened
      health by reducing opportunities for physical activity and by the proliferation
      of inexpensive calorie-dense foods. However, much of the same technology can be
      used to counter these troublesome trends by fostering the development and
      maintenance of healthy eating and physical activity habits. In contrast to
      intensive face-to-face treatments, technology-based interventions also have the
      potential to reach large numbers of individuals at low cost. The purpose of this
      review is to discuss studies in which digital technology has been used for
      behavioral weight control, report on advances in consumer technology that are
      widely adopted but insufficiently tested, and explore potential future directions
      for both. Web-based, mobile (eg, smartphone), virtual reality, and gaming
      technologies are the focus of discussion. The best evidence exists to support the
      use of digital technology for self-monitoring of weight-related behaviors and
      outcomes. However, studies are underway that will provide additional, important
      information regarding how best to apply digital technology for behavioral weight
      control. 

PMID- 24664800
TI  - In vivo administration of granulocyte colony-stimulating factor restores long
      term depression in hippocampal slices prepared from transgenic APP/PS1 mice.
AB  - Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that
      also possesses neurotrophic and antiapoptotic properties. G-CSF has been reported
      to decrease amyloid burden significantly, promote hippocampal neurogenesis, and
      improve spatial learning in a mouse model of Alzheimer's disease. To understand
      better the effects of G-CSF on hippocampal-dependent learning, the present study
      focused on electrophysiological correlates of neuroplasticity, long-term
      potentiation (LTP), and long-term depression (LTD). Two cohorts of transgenic
      APP/PS1 mice, with or without prior bone marrow transplantation from Tg GFP mice,
      were treated in vivo for 2 weeks with G-CSF or vehicle. After completion of the
      treatments, hippocampal slices were prepared for electrophysiological studies of
      LTP and LTD. LTP was induced and maintained in both G-CSF-treated and vehicle
      treated groups of Tg APP/PS1. In contrast, LTD could not be induced in vehicle
      treated Tg APP/PS1 mice, but G-CSF treatment restored LTD. The LTP and LTD
      results obtained from the cohort of bone marrow-grafted Tg APP/PS1 mice did not
      differ from those from nongrafted Tg APP/PS1 mice. The mechanism by which G-CSF
      restores LTD is not known, but it is possible that its capacity to reduce amyloid
      plaques results in increased soluble oligomers of amyloid-beta (A-beta), which in
      turn may facilitate LTD. This mechanism would be consistent with the recent
      report that soluble A-beta oligomers promote LTD in hippocampal slices.

PMID- 24664798
TI  - Long-term health outcomes in offspring born to women with diabetes in pregnancy.
AB  - In this review, we critically assess recent evidence from human studies regarding
      the potential implications of exposure to maternal diabetes in-utero for long
      term adiposity, cardiometabolic outcomes, and cognitive ability of the offspring.
      Evidence supports a direct causal role for exposure to maternal diabetes in utero
      in determining offspring long-term greater adiposity and adverse cardiometabolic
      health. Although a majority of observational studies report associations of
      exposure to maternal pregnancy diabetes with lower cognitive ability, there is
      also evidence supporting an opposite 'protective' intrauterine effect of exposure
      to maternal pregnancy diabetes on offspring cognitive ability. Epigenetic
      modification has been suggested as a mediator on the pathways from maternal
      pregnancy diabetes to long-term offspring outcomes and several recent studies
      that are reviewed here lend some support to this notion, but research in this
      area is still too novel to be conclusive. 

PMID- 24664802
TI  - Bio-inspired high-performance antireflection and antifogging polymer films.

PMID- 24664801
TI  - Glomerular filtration rate in the elderly and in the oldest old: correlation with
      frailty and mortality.
AB  - The equations for estimating kidney function have become very popular in the last
      decade. However, the clinical and prognostic meaning of these measures may be
      very different in older populations. Two cohorts of people aged 65-89 years
      (older sample) and 90 or more (oldest old sample) were used to investigate the
      prognostic significance of estimated glomerular filtration rate (eGFR).
      Additionally, we also investigated whether combining frailty and eGFR may improve
      the accuracy of frailty in predicting mortality. We found that lower eGFR values
      were significantly more frequent among frail subjects in both groups. eGFR < 30
      was associated with increased risk for all-cause mortality either in subjects
      aged 65-89 years (HR = 3.71, 95% CI = 1.23-11.2) or in those aged 90 or more (HR
      = 1.53, 95% CI = 1.05-2.23). In the latter group, a not significant trend for
      increasing mortality was also observed among people with eGFR > 60 (HR = 1.28,
      95% CI = 0.72-2.26). In addition, the oldest old subjects with eGFR > 60 and eGFR
      < 30 had the lowest hand-grip strength and ADL values. Combining eGFR and frailty
      status significantly improved the accuracy of frailty in predicting mortality
      only in the older sample. In conclusion, a U-shaped relationship exists between
      eGFR and mortality in the oldest old, but not in older individuals. Our findings
      suggest that eGFR needs to be adjusted for muscle mass/physical performance when
      estimating kidney function in people aged 90 or more. Nevertheless, in subjects
      aged 65-89 years, eGFR may improve the accuracy of frailty status in predicting
      prognosis, thus suggesting that eGFR may represent an additional dimension of
      frailty syndrome.

PMID- 24664803
TI  - Optimized flow cytometry isolation of murine spermatocytes.
AB  - Meiotic prophase I (MPI), is an initial stage of meiosis characterized by
      intricate homologous chromosome interactions, synapsis, and DNA recombination.
      These processes depend on the complex, but poorly understood early MPI events of
      homologous chromosome search, alignment, and pairing. Detailed molecular
      investigation of these early events requires isolation of individual MPI
      substages. Enrichment for Pachytene (P) and Diplotene (D) substages of late MPI
      was previously accomplished using flow cytometry. However, separation of early
      MPI spermatocytes, specifically, of Leptotene (L) and Zygotene (Z) substages, has
      been a challenge due to these cells' similar characteristics. In this report, we
      describe an optimized Hoechst-33342 (Hoechst)-based flow cytometry approach for
      isolating individual MPI populations from adult mouse testis. We get significant
      enrichment for individual L and Z spermatocytes, previously inseparable from each
      other, and optimize the isolation of other MPI substages. Our flow cytometry
      approach is a combination of three optimized strategies. The first is
      optimization of testis dissociation protocol that yields more consistent and
      reproducible testicular single cell suspension. The second involves optimization
      of flow cytometric gating protocol where a critical addition to the standard
      protocol for cell discrimination based on Hoechst fluorescence, involves a back
      gating technique based on light scattering parameters. This step specifies
      selection of individual MPI substages. The third, is an addition of DNA content
      restriction to the gating protocol to minimize contamination from non-meiotic
      cells. Finally, we confirm significant enrichment of high-purity Preleptotene
      (PreL), L, Z, P, and D MPI spermatocytes using stage-specific marker
      distribution. The technique will facilitate understanding of the molecular events
      underlying MPI.

PMID- 24664804
TI  - A newly recognized 13q12.3 microdeletion syndrome characterized by intellectual
      disability, microcephaly, and eczema/atopic dermatitis encompassing the HMGB1 and
      KATNAL1 genes.
AB  - Proximal deletions of the long arm of chromosome 13 have been reported only
      rarely. Here we present three unrelated patients with heterozygous, apparently de
      novo deletions encompassing 13q12.3. The patients present with moderate
      demonstrated or apparent intellectual disability, postnatal microcephaly, and
      eczema/atopic dermatitis as the predominant symptoms. In addition, they had
      pronounced feeding difficulties in early infancy. They displayed similar facial
      features such as malar flattening, a prominent nose with underdeveloped alae
      nasi, a smooth philtrum, and a thin vermillion of the upper lip. The proximal and
      distal breakpoints were clustered and the deletions spanned from 1.4 to 1.7 Mb,
      comprising at least 11 RefSeq genes. However, heterozygous deletions partially
      overlapping those observed in the present patients have been described in healthy
      parents of patients with Peters-Plus syndrome, an autosomal recessive disorder
      caused by inactivation of the B3GALTL gene. We therefore propose that the
      critical region of the 13q12.3 microdeletion syndrome contains only three genes,
      namely, KATNAL1, HMGB1, and LINC00426, a non-protein coding RNA. The KATNAL1
      protein belongs to a family of microtubule severing enzymes that have been
      implicated in CNS plasticity in experimental models, but little is known about
      its function in humans. The HMGB1 protein is an evolutionarily conserved
      chromatin-associated protein involved in many biologically important processes.
      In summary, we propose that microdeletion 13q12.3 represents a novel clinically
      recognizable condition and that the microtubule severing gene KATNAL1 and the
      chromatin-associated gene HMGB1 are candidate genes for intellectual disability
      inherited in an autosomal dominant pattern.

PMID- 24664806
TI  - Fragmentation of electrospray-produced deprotonated ions of
      oligodeoxyribonucleotides containing an alkylated or oxidized thymidine.
AB  - Alkylation and oxidation constitute major routes of DNA damage induced by
      endogenous and exogenous genotoxic agents. Understanding the biological
      consequences of DNA lesions often necessitates the availability of
      oligodeoxyribonucleotide (ODN) substrates harboring these lesions, and sensitive
      and robust methods for validating the identities of these ODNs. Tandem mass
      spectrometry is well suited for meeting these latter analytical needs. In the
      present study, we evaluated how the incorporation of an ethyl group to different
      positions (i.e., O(2), N3, and O(4)) of thymine and the oxidation of its 5-methyl
      carbon impact collisionally activated dissociation (CAD) pathways of electrospray
      produced deprotonated ions of ODNs harboring these thymine modifications. Unlike
      an unmodified thymine, which often manifests poor cleavage of the C3'-O3' bond,
      the incorporation of an alkyl group to the O(2) position and, to a much lesser
      extent, the O(4) position, but not the N3 position of thymine, led to facile
      cleavage of the C3'-O3' bond on the 3' side of the modified thymine. Similar
      efficient chain cleavage was observed when thymine was oxidized to 5-formyluracil
      or 5-carboxyluracil, but not 5-hydroxymethyluracil. Additionally, with the
      support of computational modeling, we revealed that proton affinity and acidity
      of the modified nucleobases govern the fragmentation of ODNs containing the
      alkylated and oxidized thymidine derivatives, respectively. These results
      provided important insights into the effects of thymine modifications on ODN
      fragmentation.

PMID- 24664805
TI  - Instrumental variable applications using nursing home prescribing preferences in
      comparative effectiveness research.
AB  - PURPOSE: Nursing home residents are of particular interest for comparative
      effectiveness research given their susceptibility to adverse treatment effects
      and systematic exclusion from trials. However, the risk of residual confounding
      because of unmeasured markers of declining health using conventional analytic
      methods is high. We evaluated the validity of instrumental variable (IV) methods
      based on nursing home prescribing preference to mitigate such confounding, using
      psychotropic medications to manage behavioral problems in dementia as a case
      study. METHODS: A cohort using linked data from Medicaid, Medicare, Minimum Data
      Set, and Online Survey, Certification and Reporting for 2001-2004 was
      established. Dual-eligible patients >=65 years who initiated psychotropic
      medication use after admission were selected. Nursing home prescribing preference
      was characterized using mixed-effects logistic regression models. The
      plausibility of IV assumptions was explored, and the association between
      psychotropic medication class and 180-day mortality was estimated. RESULTS: High
      prescribing and low-prescribing nursing homes differed by a factor of 2. Each
      preference-based IV measure described a substantial proportion of variation in
      psychotropic medication choice (beta(IV -> treatment): 0.22-0.36). Measured
      patient characteristics were well balanced across patient groups based on
      instrument status (52% average reduction in Mahalanobis distance). There was no
      evidence that instrument status was associated with markers of nursing home
      quality of care. CONCLUSION: Findings indicate that IV analyses using nursing
      home prescribing preference may be a useful approach in comparative effectiveness
      studies, and should extend naturally to analyses including untreated comparison
      groups, which are of great scientific interest but subject to even stronger
      confounding.

PMID- 24664807
TI  - Glycan side reaction may compromise ETD-based glycopeptide identification.
AB  - Tris(hydroxymethyl)aminomethane (Tris) is one of the most frequently used buffer
      ingredients. Among other things, it is recommended and is usually used for lectin
      based affinity enrichment of glycopeptides. Here we report that sialic acid, a
      common 'capping' unit in both N- and O-linked glycans may react with this
      chemical, and this side reaction may compromise glycopeptide identification when
      ETD spectra are the only MS/MS data used in the database search. We show that the
      modification may alter N- as well as O-linked glycans, the Tris-derivative is
      still prone to fragmentation both in 'beam-type' CID (HCD) and ETD experiments,
      at the same time--since the acidic carboxyl group was 'neutralized'--it will
      display a different retention time than its unmodified counterpart. We also
      suggest solutions that--when incorporated into existing search engines--may
      significantly improve the reliability of glycopeptide assignments.

PMID- 24664808
TI  - Fragmentation characteristics of deprotonated N-linked glycopeptides: influences
      of amino acid composition and sequence.
AB  - Glycopeptide structural analysis using tandem mass spectrometry is becoming a
      common approach for elucidating site-specific N-glycosylation. The analysis is
      generally performed in positive-ion mode. Therefore, fragmentation of protonated
      glycopeptides has been extensively investigated; however, few studies are
      available on deprotonated glycopeptides, despite the usefulness of negative-ion
      mode analysis in detecting glycopeptide signals. Here, large sets of
      glycopeptides derived from well-characterized glycoproteins were investigated to
      understand the fragmentation behavior of deprotonated N-linked glycopeptides
      under low-energy collision-induced dissociation (CID) conditions. The fragment
      ion species were found to be significantly variable depending on their amino acid
      sequence and could be classified into three types: (i) glycan fragment ions, (ii)
      glycan-lost fragment ions and their secondary cleavage products, and (iii)
      fragment ions with intact glycan moiety. The CID spectra of glycopeptides having
      a short peptide sequence were dominated by type (i) glycan fragments (e.g.,
      (2,4)AR, (2,4)AR-1, D, and E ions). These fragments define detailed structural
      features of the glycan moiety such as branching. For glycopeptides with medium or
      long peptide sequences, the major fragments were type (ii) ions (e.g., [peptide +
      (0,2)X0-H](-) and [peptide-NH3-H](-)). The appearance of type (iii) ions strongly
      depended on the peptide sequence, and especially on the presence of Asp, Asn, and
      Glu. When a glycosylated Asn is located on the C-terminus, an interesting
      fragment having an Asn residue with intact glycan moiety, [glycan + Asn-36](-),
      was abundantly formed. Observed fragments are reasonably explained by a
      combination of existing fragmentation rules suggested for N-glycans and peptides.

PMID- 24664809
TI  - LC-MS/MS peptide mapping with automated data processing for routine profiling of
      N-glycans in immunoglobulins.
AB  - Protein N-Glycan analysis is traditionally performed by high pH anion exchange
      chromatography (HPAEC), reversed phase liquid chromatography (RPLC), or
      hydrophilic interaction liquid chromatography (HILIC) on fluorescence-labeled
      glycans enzymatically released from the glycoprotein. These methods require time
      consuming sample preparations and do not provide site-specific glycosylation
      information. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) peptide
      mapping is frequently used for protein structural characterization and, as a
      bonus, can potentially provide glycan profile on each individual glycosylation
      site. In this work, a recently developed glycopeptide fragmentation model was
      used for automated identification, based on their MS/MS, of N-glycopeptides from
      proteolytic digestion of monoclonal antibodies (mAbs). Experimental conditions
      were optimized to achieve accurate profiling of glycoforms. Glycan profiles
      obtained from LC-MS/MS peptide mapping were compared with those obtained from
      HPAEC, RPLC, and HILIC analyses of released glycans for several mAb molecules.
      Accuracy, reproducibility, and linearity of the LC-MS/MS peptide mapping method
      for glycan profiling were evaluated. The LC-MS/MS peptide mapping method with
      fully automated data analysis requires less sample preparation, provides site
      specific information, and may serve as an alternative method for routine
      profiling of N-glycans on immunoglobulins as well as other glycoproteins with
      simple N-glycans. 

PMID- 24664810
TI  - Screening of complicated matrixes with paper assisted ultrasonic spray ionization
      mass spectrometry.
AB  - To analyze compounds in complicated matrixes using mass spectrometry, we describe
      a novel ambient ionization approach, termed paper assisted ultrasonic spray
      ionization (PAUSI). The ionization process is based on the ultrasonic vibration
      of the piezoelectric ceramic disk, on which the samples are placed. Porous
      materials are utilized to generate fine initial droplet, which could alleviate
      matrix effect during ionization process for complicated matrix. PAUSI was
      evaluated as an attractive tool to screen analytes from complicated matrixes,
      such as (1) bovine serum with NaCl 150 g/L, (2) viscous samples, and (3)
      biological fluid, without any sample preparation. Moreover, it provides great
      advantage in simplifying the mass spectrometry analysis process, and the
      ionization device is inexpensive and easy to operate. 

PMID- 24664811
TI  - Social support in late life mania: GERI-BD.
AB  - OBJECTIVE: Using the database of the National Institute of Mental Health
      sponsored acute treatment of late life mania study (GERI-BD), we assessed the
      role of social support in the presentation of late life bipolar mania. METHODS:
      In the first 100 subjects randomized in geriatric BD, we explored the
      demographic, clinical, and social support characteristics (assessed using the
      Duke Social Support Index) and aspects of manic presentation. We selected two
      dependent variables: symptom severity, as determined by the Young Mania Rating
      Scale (YMRS) at baseline, and duration of episode. We selected nine potential
      independent variables on the basis of Pearson correlation coefficients. We
      derived two final models using multiple regression analysis employing an
      iterative process. RESULTS: In our severity model, being married was associated
      with a higher YMRS score (p = 0.05), whereas higher social interaction scores
      with non-family members were associated with a lower YMRS score (p = 0.011). In
      the episode duration model, longer duration was associated with a higher Hamilton
      Depression Rating Scale score (p = 0.03) and higher social interaction scores
      with non-family members (p = 0.0003), younger age (p = 0.04), higher number of
      persons in one's family social network (p = 0.017), and higher instrumental
      support scores (p = 0.0062). CONCLUSIONS: In late life mania, more social
      interaction with one's community appears to be associated with less severe
      symptoms at presentation for treatment, however, it can also be associated with
      slightly longer the duration of episode. Two aspects of the Duke Social Support
      Index are associated with a shorter episode duration prior to seeking treatment:
      being part of a larger family network and a having a higher level of instrumental
      support prior to treatment. The Instrumental Support Subscale measures the degree
      of assistance that is available for the respondent in performing daily tasks.
      These findings suggest that in older adults with BD, close social interactions
      and support are important in limiting the length of the illness episode prior to
      treatment. Social interactions involving non-family members may be less important
      in moderating the intensity of the symptoms at presentation.

PMID- 24664812
TI  - An optimal frequency range for assessing the pressure reactivity index in
      patients with traumatic brain injury.
AB  - The objective of this study was to identify the optimal frequency range for
      computing the pressure reactivity index (PRx). PRx is a clinical method for
      assessing cerebral pressure autoregulation based on the correlation of
      spontaneous variations of arterial blood pressure (ABP) and intracranial pressure
      (ICP). Our hypothesis was that optimizing the methodology for computing PRx in
      this way could produce a more stable, reliable and clinically useful index of
      autoregulation status. The patients studied were a series of 131 traumatic brain
      injury patients. Pressure reactivity indices were computed in various frequency
      bands during the first 4 days following injury using bandpass filtering of the
      input ABP and ICP signals. Patient outcome was assessed using the extended
      Glasgow Outcome Scale (GOSe). The optimization criterion was the strength of the
      correlation with GOSe of the mean index value over the first 4 days following
      injury. Stability of the indices was measured as the mean absolute deviation of
      the minute by minute index value from 30-min moving averages. The optimal index
      frequency range for prediction of outcome was identified as 0.018-0.067 Hz
      (oscillations with periods from 55 to 15 s). The index based on this frequency
      range correlated with GOSe with rho=-0.46 compared to -0.41 for standard PRx, and
      reduced the 30-min variation by 23%.

PMID- 24664813
TI  - BTNL2 associated with the immune response to hepatitis B vaccination in a Chinese
      Han population.
AB  - No response to hepatitis B vaccination is a complex phenomenon, which is induced
      by the combinations of environmental and genetic factors. The aim of the study
      was to investigate the association between the polymorphisms of the butyrophilin
      like 2 (BTNL2) gene and the immune response to hepatitis B vaccination in a
      Chinese Han population. A total of 7 single nucleotide polymorphisms in the BTNL2
      gene were analyzed in 566 non-responders and 1,040 high-responders to hepatitis B
      vaccination. The alleles T, T, C, A, G of rs3763316, rs3763311, rs9268494,
      rs3806156, and rs2076530 were associated with no response to hepatitis B
      vaccination (P = 0.015, odds ratio (OR) = 1.20; P = 0.029, OR = 1.18; P = 2.00E
      07, OR = 1.58; P = 0.002, OR = 1.27; P = 2.90E-06, OR = 1.41, respectively).
      Whereas, the alleles T, C of rs9268501 and rs3763313 played significantly
      protective roles in the immune response to hepatitis B vaccination (P = 0.007, OR
      = 0.81; P = 0.004, OR = 0.74). Besides, the risks of no response to hepatitis B
      vaccination were increased significantly among individuals harbored the
      haplotypes of G-T-A-T-C-A-G (P = 0.038, OR = 1.48), G-T-A-T-C (P < 0.0001, OR =
      2.34), A-A (P < 0.0001, OR = 4.08), and C-G (P < 0.0001, OR = 4.75). However, the
      haplotype of G-C-A-T-C (P = 1.00E-04, OR = 0.54) exhibited a protective role in
      the immune response to hepatitis B vaccination in the study. These findings
      suggest that polymorphisms in the BTNL2 gene might play a vital role in
      determining the outcome of the immune response to hepatitis B vaccination.

PMID- 24664814
TI  - Palladium-catalyzed stereoselective intramolecular oxidative amidation of alkenes
      in the synthesis of 1,3- and 1,4-amino alcohols and 1,3-diamines.
AB  - An efficient and practical Pd-catalyzed intramolecular oxidative allylic
      amidation provides facile access to derivatives of 1,3- and 1,4-amino alcohols
      and 1,3-diamines. The method operates under mild reaction conditions (RT) with
      molecular oxygen (1 atm) as the sole reoxidant of Pd. Excellent
      diastereoselectivities were attained with substrates bearing a secondary
      stereogenic center.

PMID- 24664815
TI  - Arterial and venous thrombosis of the cerebral vasculature in GAPO syndrome.
AB  - A 37-year-old male, previously diagnosed with GAPO syndrome, was admitted to our
      hospital complaining of recurrent episodes of transient weakness and numbness in
      his left arm for 3 months, and severe headache with progressive dysphagia for 15
      days. His cranial magnetic resonance (MR) images showed multiple ischemic foci in
      the bilateral periventricular and supraventricular white matter. Cerebral MR
      angiography showed total occlusion of the right internal carotid artery and
      moderate stenosis in the left internal carotid. We also detected chronic
      thrombotic changes in the distal left sigmoid sinus, proximal right sigmoid
      sinus, and bilateral jugular veins on cerebral MR-venography. He was diagnosed
      with dilated cardiomyopathy at age 31 years, which was reported as a novel
      association; and later he had a myocardial infarction at age 34 years. To the
      best of our knowledge, this is the first patient with GAPO syndrome and arterial
      atherosclerosis in cerebral-as well as coronary-arteries and intracranial venous
      thrombosis. We report the evolution of the disease in this patient, who died at
      age 38 years due to respiratory failure secondary to lower respiratory tract
      infection.

PMID- 24664816
TI  - Highly stretchable polymer transistors consisting entirely of stretchable device
      components.

PMID- 24664817
TI  - The limited number of available nucleotide and protein sequence data from the
      recent H7N9 cases in China impeded investigation and characterization of the
      outbreak.

PMID- 24664818
TI  - Sustainability of rituximab therapy in different treatment strategies: results of
      a 3-year followup of a German biologics register.
AB  - OBJECTIVE: To compare the approved treatment of rheumatoid arthritis using
      rituximab + methotrexate (RTX + MTX) versus the off-label treatment variants of
      RTX in monotherapy or RTX in combination with leflunomide (RTX + LEF). METHODS:
      We included RTX-naive patients enrolled in the German biologics register RABBIT
      (Rheumatoid Arthritis: Observation of Biologic Therapy) between 2007 and 2012 (n
      = 907) who started treatment with RTX. Three treatment regimens (RTX + MTX, RTX +
      LEF, and RTX monotherapy) were analyzed regarding therapy discontinuation,
      dropout, RTX retreatment, and concomitant glucocorticoid therapy. Effectiveness
      was evaluated with linear mixed models. RESULTS: Baseline patient characteristics
      were similar across treatment regimens, except for poorer functional status and
      more comorbidities in RTX monotherapy. Average doses of glucocorticoids were
      lower in RTX + LEF compared to the 2 other groups. The frequency and timing of
      RTX retreatment (P > 0.62) as well as improvement in the Disease Activity Score
      in 28 joints (DAS28) over time (P > 0.15) were similar in all treatment regimens.
      Within the first 12 months of treatment, the DAS28 decreased by 1.5 units, and
      between months 12 and 36, by a further 0.4 unit equally in all groups.
      Nevertheless, therapy discontinuation and dropout were significantly increased on
      RTX monotherapy (hazard ratio [HR] 1.7 [95% confidence interval (95% CI) 1.2
      2.3]), and additionally when patients were rheumatoid factor negative (HR 1.5
      [95% CI 1.0-2.1]). CONCLUSION: In patients who continue therapy, RTX + LEF, RTX
      monotherapy, and RTX + MTX seem to be equally effective. However, given the lower
      adherence rates on monotherapy, this treatment option is not sufficient for all
      patients. Since many patients are intolerant to MTX, more licensed RTX treatment
      options are needed.

PMID- 24664819
TI  - Detection of Clostridium difficile diarrhoea in Harare, Zimbabwe.
AB  - BACKGROUND: Clostridium difficile is associated with nosocomial and community
      acquired diarrhoea and pseudomembranous colitis in humans. Little information is
      available on the importance of C. difficile as a causative agent of diarrhoea in
      developing countries such as Zimbabwe. The current study was carried out to
      determine the prevalence of C. difficile in diarrhoeal stools of outpatients over
      2 years of age presenting at healthcare centres in Harare, Zimbabwe, and to
      determine the antimicrobial susceptibility of the isolates. METHODS: Toxigenic
      stool culture was used in this study. Diarrhoeal stool specimens were cultured
      for C. difficile, followed by direct immunoassay on colonies of positive cultures
      with significant growth to detect toxins A or B. RESULTS: C. difficile was
      detected in 8.6% (n=23) of the 268 diarrhoeal stool specimens. All C. difficile
      isolates were susceptible to metronidazole, vancomycin, chloramphenicol and
      doxycyline, and resistant to clindamycin, ciprofloxacin, gentamicin and
      cefotaxime. About 70% of the isolates were resistant to co-trimoxazole.
      CONCLUSIONS: C. difficile was observed to be an important diarrhoeal pathogen and
      metronidazole was effective in treating diarrhoea caused by the bacterium. Co
      trimoxazole, which is widely used as prophylaxis against opportunistic infections
      in HIV/AIDS patients, was not very effective in preventing diarrhoea caused by C.
      difficile.

PMID- 24664820
TI  - Allogeneic stem cell transplantation for acute myeloid leukemia in first complete
      remission: are we closer to knowing who needs it?
AB  - Acute myeloid leukemia (AML) is a very heterogeneous disease. Prognosis is
      related not only to intrinsic characteristics such as cytogenetics and molecular
      markers, but also the patient's ability to tolerate therapy, and treatment
      response. Allogeneic stem cell transplantation (allo-HCT) has been traditionally
      indicated for poor-risk disease in first complete remission (CR1) or for
      treatment of relapsed or refractory AML. 'Poor-risk' disease is now better
      defined due to genetic subtyping, particularly in chromosomally normal AML. In
      addition, the presence of comorbid conditions should be included in the decision
      making process. Improvements in supportive care and the use of modern
      conditioning regimens have been associated with improved outcomes, mostly due to
      a reduction in treatment-related mortality. Therefore, a significant proportion
      of patients with AML-CR1 can potentially benefit from allo-HCT. We give general
      guidelines on how to incorporate cytogenetic and molecular risk factors, donor
      selection, and patient characteristics in order to determine when allo-HCT should
      be indicated in CR1. 

PMID- 24664821
TI  - Integrated chip-based physiometer for automated fish embryo toxicity biotests in
      pharmaceutical screening and ecotoxicology.
AB  - Transgenic zebrafish (Danio rerio) models of human diseases have recently emerged
      as innovative experimental systems in drug discovery and molecular pathology.
      None of the currently available technologies, however, allow for automated
      immobilization and treatment of large numbers of spatially encoded transgenic
      embryos during real-time developmental analysis. This work describes the proof-of
      concept design and validation of an integrated 3D microfluidic chip-based system
      fabricated directly in the poly(methyl methacrylate) transparent thermoplastic
      using infrared laser micromachining. At its core, the device utilizes an array of
      3D micromechanical traps to actively capture and immobilize single embryos using
      a low-pressure suction. It also features built-in piezoelectric microdiaphragm
      pumps, embryo-trapping suction manifold, drug delivery manifold, and optically
      transparent indium tin oxide heating element to provide optimal temperature
      during embryo development. Furthermore, we present design of the proof-of-concept
      off-chip electronic interface equipped with robotic servo actuator driven stage,
      innovative servomotor-actuated pinch valves, and embedded miniaturized
      fluorescent USB microscope. Our results showed that the innovative device has
      100% embryo-trapping efficiency while supporting normal embryo development for up
      to 72 hr in a confined microfluidic environment. We also showed data that this
      microfluidic system can be readily applied to kinetic analysis of a panel of
      investigational antiangiogenic agents in transgenic zebrafish lines. The optical
      transparency and embryo immobilization allow for convenient visualization of
      developing vasculature patterns in response to drug treatment without the need
      for specimen re-positioning. The integrated electronic interfaces bring the lab
      on-a-chip systems a step closer to realization of complete analytical automation.

PMID- 24664822
TI  - Methods for dynamic investigations of surface-attached in vitro bacterial and
      fungal biofilms.
AB  - Three dynamic models for the investigation of in vitro biofilm formation are
      described in this chapter. In the 6-well plate assay presented here, the placing
      of the plate on a rotating platform provides shear, thereby making the system
      dynamic with respect to the static microtiter assay.The second reported model,
      especially suitable for harvesting high amounts of cells for transcriptomic or
      proteomic investigations, is based on numerous glass beads placed in a flask
      incubated with shaking on a rotating platform, thus increasing the surface area
      for biofilm formation. Finally, the flow-cell system, that is the driving model
      for elucidating the biofilm-forming process in vitro as well as the biofilm
      tolerance towards antibiotics and host defense components, is illustrated here. 

PMID- 24664823
TI  - Aqueous two-phase system technology for patterning bacterial communities and
      biofilms.
AB  - We describe a novel method which makes use of polymer-based aqueous two-phase
      systems to pattern bacterial communities inside Petri dishes. This method allows
      us to culture submillimeter-sized bacterial communities in spatially distinct
      spots while maintaining a degree of chemical connectedness to each other through
      the aqueous phase. Given sufficient time, these bacterial cultures develop
      biofilms, each corresponding to the footprint of the droplet spot. This method
      can be used to study the interactions between bacterial communities and biofilms
      spotted adjacent to each other. Furthermore, it can be extended to study the
      interactions between different bacterial communities and an underlying epithelial
      cell layer. 

PMID- 24664824
TI  - Quorum sensing in gram-positive bacteria: assay protocols for staphylococcal agr
      and enterococcal fsr systems.
AB  - A thiolactone/lactone peptide-mediated quorum sensing (QS) system is commonly
      employed in gram-positive bacteria to control the expression of a variety of
      phenotypes, including the production of virulence factors and biofilm formation.
      Here, we describe assay protocols for the well-studied QS systems (agr and fsr)
      of two representative gram-positive pathogens, Staphylococcus aureus and
      Enterococcus faecalis. These convenient assay systems are useful for the
      screening of QS inhibitors as well as for basic research to address the mechanism
      of these QS systems. 

PMID- 24664825
TI  - Advanced techniques for in situ analysis of the biofilm matrix (structure,
      composition, dynamics) by means of laser scanning microscopy.
AB  - The extracellular constituents in bioaggregates and biofilms can be imaged four
      dimensionally by using laser scanning microscopy. In this protocol we provide
      guidance on how to examine the various extracellular compartments in between
      microbial cells and communities associated with interfaces. The current options
      for fluorescence staining of matrix compounds and extracellular microhabitats are
      presented. Furthermore, practical aspects are discussed and useful notes are
      added. The chapter ends with a brief introduction to other approaches for EPS
      analysis and an outlook for future needs.

PMID- 24664826
TI  - Multiplex fluorescence in situ hybridization (M-FISH) and confocal laser scanning
      microscopy (CLSM) to analyze multispecies oral biofilms.
AB  - Multiplex fluorescence in situ hybridization (M-FISH) constitutes a favorable
      microbiological method for the analysis of spatial distribution of highly
      variable phenotypes found in multispecies oral biofilms. The combined use of
      confocal laser scanning microscopy (CLSM) produces high-resolution three
      dimensional (3D) images of individual bacteria in their natural environment.
      Here, we describe the application of M-FISH on early (Streptococcus spp.,
      Actinomyces naeslundii) and late colonizers (Fusobacterium nucleatum, Veillonella
      spp.) of in situ-formed oral biofilms, the acquisition of CLSM images, as well as
      the qualitative and quantitative analysis of these digitally obtained and
      processed images.

PMID- 24664827
TI  - Field emission scanning electron microscopy of biofilm-growing bacteria involved
      in nosocomial infections.
AB  - Scanning electron microscopy (SEM) provides useful information on the shape,
      size, and localization within the biofilm of single bacteria as well as on the
      steps of biofilm formation process, on bacterial interactions, and on production
      of extracellular polymeric substances.When biofilms are constituted by microbial
      species involved in health care-associated infections, information provided by
      SEM can be fruitfully used not only for basic researches but also for diagnostic
      purposes.The protocols currently used in our laboratory for biofilm investigation
      by SEM are reported here. Particularly, the procedures to fix, dehydrate, and
      metalize in vitro-developed biofilms or ex vivo clinical specimens colonized by
      biofilm-growing microorganisms are described as well as the advantages of the
      observation of these samples by field emission scanning electron microscopy. 

PMID- 24664828
TI  - Experimental approaches to investigating the vaginal biofilm microbiome.
AB  - Unraveling the complex ecology of the vaginal biofilm microbiome relies on a
      number of complementary techniques. Here, we describe the experimental approaches
      for studying vaginal microbial biofilm samples with a focus on specimen
      preparation for subsequent analysis. The techniques include fluorescence
      microscopy, fluorescence in situ hybridization, and scanning and transmission
      electron microscopy. Isolation of microbial DNA and RNA from these samples is
      covered along with a brief discussion of chemical analysis methods. 

PMID- 24664829
TI  - Imaging bacteria and biofilms on hardware and periprosthetic tissue in orthopedic
      infections.
AB  - Infection is a major complication of total joint arthroplasty (TJA) surgery, and
      even though it is now as low as 1 % in some hospitals, the increasing number of
      primary surgeries translates to tens of thousands of revisions due to prosthetic
      joint infection (PJI). In many cases the only solution is revision surgery in
      which the hardware is removed. This process is extremely long and painful for
      patients and is a considerable financial burden for the health-care system. A
      significant proportion of the difficulties in diagnosis and treatment of PJI are
      associated with biofilm formation where bacteria attach to the surface of the
      prosthesis and periprosthetic tissue and build a 3-D biofilm community encased in
      an extracellular polymeric slime (EPS) matrix. Bacteria in biofilms have a low
      metabolic rate which is thought to be a major contributor to their recalcitrance
      to antibiotic treatment. The diagnosis of biofilm infections is difficult due to
      the fact that bacteria in biofilms are not readily cultured with standard
      clinical microbiology techniques. To identify and visualize in situ biofilm
      bacteria in orthopedic samples, we have developed protocols for the collection of
      samples in the operating room, for molecular fluorescent staining with 16S rRNA
      fluorescence in situ hybridization (FISH), and for imaging of samples using
      confocal laser scanning microscopy (CLSM). Direct imaging is the only method
      which can definitively identify biofilms on implants and complements both culture
      and culture-independent diagnostic methods.

PMID- 24664830
TI  - Animal models to evaluate bacterial biofilm development.
AB  - Medical biofilms have attracted substantial attention especially in the past
      decade. Animal models are contributing significantly to understand the
      pathogenesis of medical biofilms. In addition, animal models are an essential
      tool in testing the hypothesis generated from clinical observations in patients
      and preclinical testing of agents showing in vitro antibiofilm effect. Here, we
      describe three animal models - two non-foreign body Pseudomonas aeruginosa
      biofilm models and a foreign body Staphylococcus aureus model. 

PMID- 24664831
TI  - Animal models to investigate fungal biofilm formation.
AB  - Microbial biofilms play an essential role in several infectious diseases and are
      defined as extensive communities of sessile organisms irreversibly associated
      with a surface, encased within a polysaccharide-rich extracellular matrix (ECM),
      and exhibiting enhanced resistance to antimicrobial drugs. Forming a biofilm
      provides the microbes protection from environmental stresses due to contaminants,
      nutritional depletion, or imbalances, but is dangerous to human health due to
      their inherent robustness and elevated resistance.The use of indwelling medical
      devices (e.g., central venous catheters, CVCs) in current therapeutic practice is
      associated with 80-90 % of hospital-acquired bloodstream and deep tissue
      infections. Most cases of catheter-related bloodstream infections (CRBSIs)
      involve colonization of microorganisms on catheter surfaces where they form a
      biofilm. Additionally, Fusarium solani and F. oxysporum were the causative
      organisms of the 2005/2006 outbreak of contact lens-associated fungal keratitis
      in the United States, Europe, the UK, and Singapore, and these infections
      involved formation of biofilms on contact lens. Fungal biofilm formation is
      studied using a number of techniques, involving the use of a wide variety of
      substrates and growth conditions. In vitro techniques involving the use of
      confocal scanning laser/scanning electron microscopy, metabolic activity assay,
      dry weight measurements, and antifungal susceptibility assays are increasingly
      used by investigators to quantify and evaluate biofilm morphology. However, there
      are not many in vivo models used to validate biofilm-associated infections. In
      this protocol, we describe a clinically relevant rabbit model of C. albicans
      biofilm-associated catheter infection to evaluate the morphology, topography, and
      architecture of fungal biofilms. We also describe a murine model of contact lens
      associated Fusarium keratitis.Evaluation of the formation of fungal biofilms on
      catheters in vivo, their analysis using scanning electron microscopy (SEM) and
      quantitative catheter culture (QCC), and treatment of biofilms using
      antimicrobial lock therapy can be completed in ~20-25 days using the described
      methods. The rabbit model has utility in evaluating the efficacy of lock
      solutions. In addition, the murine model of contact lens-associated Fusarium
      keratitis enables characterizing/comparing the formation of Fusarium biofilms on
      contact lenses in vitro and determining their role in vivo.

PMID- 24664832
TI  - Nonmammalian model systems to investigate fungal biofilms.
AB  - Medical advances have resulted in an increase in the number of patients in
      immunocompromised states, vulnerable to infection, or individuals fitted with
      medical devices that form niches for microbial infections. These infections are
      difficult to treat and have significant morbidity and mortality rates. An
      important factor in the pathogenesis of fungal diseases is the development of
      biofilm-forming communities, enabling the invasion of host tissues and resistance
      to antimicrobial compounds. To investigate the genetic requirements for
      filamentation and seek compounds that inhibit the process, invertebrate hosts are
      employed as models of in vivo infection. The purpose of our review is to
      highlight methods that can be utilized to investigate fungal filamentation, an
      important step in the development of biofilms, in the invertebrate hosts Galleria
      mellonella, Caenorhabditis elegans, and Drosophila melanogaster. 

PMID- 24664833
TI  - Microbiological methods for target-oriented screening of biofilm inhibitors.
AB  - The ability of many pathogenic bacteria to grow as a biofilm results in lower
      susceptibility to antibiotic treatments and to the host immune response, thus
      leading to the development of chronic infections. The understanding that biofilms
      can play an important role in bacterial virulence has prompted the search for
      inhibitors of biofilm development and of biofilm-related cellular processes. In
      this report, we present two examples of target-based microbiological screenings
      for antimicrobials endowed with anti-biofilm activity, aimed respectively at the
      inhibition of the signal molecule cyclic di-GMP and of quorum sensing. 

PMID- 24664834
TI  - In vitro screening of antifungal compounds able to counteract biofilm
      development.
AB  - Fungi are able to grow as a single-species or a more complex biofilm attached to
      inert surfaces (catheters...) or tissues (lung...). This last form is a microbial
      niche which must be considered as a major risk factor of developing a human
      fungal infection. Nowadays, only a few therapeutic agents have been shown to be
      active against fungal biofilms in vitro and/or in vivo. So there is a real need
      to find new anti-biofilm molecules. Here we describe in detail some rapid, 96
      well microtiter plate-based methods, for the screening of compounds with anti
      biofilm activity against Candida spp. yeasts. Two approaches will be considered:
      prophylactic or curative effects of the tested compounds by producing biofilms on
      two supports - polystyrene well surfaces and catheter sections.

PMID- 24664835
TI  - Biofilm matrix-degrading enzymes.
AB  - Polymeric substances such as proteins, polysaccharides, and DNA constitute a
      major component of the biofilm matrix. Enzymes that depolymerize and degrade
      these components are useful tools for investigating the composition and function
      of the biofilm matrix. This chapter provides a brief overview of the most
      commonly used biofilm matrix-degrading enzymes and presents examples of their
      applications in biofilm research. 

PMID- 24664836
TI  - Efficacy evaluation of antimicrobial drug-releasing polymer matrices.
AB  - To assay in vitro antimicrobial activity of substances such as antibiotics or
      antiseptics, standard methods both in liquid and on solid media are available.
      These procedures cannot be adequate for testing antimicrobial-releasing or
      biocidal polymer systems.This chapter is focused on the description of methods
      that the authors have developed to evaluate the antimicrobial activity of either
      antimicrobial agent-releasing polymers or biocidal polymers. These assays can be
      applied to different types of water-soluble or insoluble polymer matrices. 

PMID- 24664837
TI  - Antibiotic polymeric nanoparticles for biofilm-associated infection therapy.
AB  - Polymeric nanoparticles are highly attractive as drug delivery vehicles due to
      their high structural integrity, stability during storage, ease of preparation
      and functionalization, and controlled release capability. Similarly, lipid
      polymer hybrid nanoparticles, which retain the benefits of polymeric
      nanoparticles plus the enhanced biocompatibility and prolonged circulation time
      owed to the lipids, have recently emerged as a superior alternative to polymeric
      nanoparticles. Drug nanoparticle complex prepared by electrostatic interaction of
      oppositely charged drug and polyelectrolytes represents another type of polymeric
      nanoparticle. This chapter details the preparation, characterization, and
      antibiofilm efficacy testing of antibiotic-loaded polymeric and hybrid
      nanoparticles and antibiotic nanoparticle complex.

PMID- 24664839
TI  - Contribution of confocal laser scanning microscopy in deciphering biofilm
      tridimensional structure and reactivity.
AB  - Confocal laser scanning microscopy (CLSM) became in last years an invaluable
      technique to study biofilms since it enables researchers to explore noninvasively
      the dynamic architecture and the reactivity of these biological edifices. The
      constant development of fluorescent markers and genetic tools along with the
      improvement of spatial, spectral, and temporal resolution of imaging facilities
      offers new opportunities to better decipher microbial biofilm properties. In this
      contribution, we proposed to describe the contribution of CLSM to the study of
      biofilm architecture and reactivity throughout two different illustrative
      approaches.

PMID- 24664838
TI  - Pharmacokinetics and pharmacodynamics of antibiotics in biofilm infections of
      Pseudomonas aeruginosa in vitro and in vivo.
AB  - Although progress on biofilm research has been obtained during the past decades,
      the treatment of biofilm infections with antibiotics remains a riddle. The
      pharmacokinetic (PK) and pharmacodynamic (PD) profiles of an antimicrobial agent
      provide important information helping to establish an efficient dosing regimen
      and to minimize the development of antimicrobial tolerance and resistance in
      biofilm infections. Unfortunately, most previous PK/PD studies of antibiotics
      have been done on planktonic cells, and extrapolation of the results on biofilms
      is problematic as bacterial biofilms differ from planktonic grown cells in the
      growth rate, gene expression, and metabolism. Here, we set up several protocols
      for the studies of PK/PD of antibiotics in biofilm infections of P. aeruginosa in
      vitro and in vivo. It should be underlined that none of the protocols in biofilms
      have yet been certificated for clinical use or proved useful for guidance of
      antibiotic therapy.

PMID- 24664840
TI  - Chip calorimetry for evaluation of biofilm treatment with biocides, antibiotics,
      and biological agents.
AB  - Any growth or bioconversion in biofilms is accompanied by the release of heat.
      The heat (in J) is tightly related to the stoichiometry of the respective process
      via law of Hess, and the heat production rate (in W or J/s) is additionally
      related to the process kinetics. This heat and the heat production rate can
      nowadays be measured by modern calorimetry with extremely high sensitivity. Flow
      through calorimetry allows the measurement of bioprocesses in biofilms in real
      time, without the need of invasive sample preparation and disturbing of biofilm
      processes. Furthermore, it can be applied for long-term measurements and is even
      applicable to turbid media. Chip or miniaturized calorimeters have the additional
      advantages of extremely short thermal equilibration times and the requirement of
      very small amounts of media and chemicals. The precision of flow-through chip
      calorimeters (about 3 mW/L) allows the detection of early stages of biofilm
      development (about 10(5) bacteria cm(-2)). 

PMID- 24664841
TI  - Bacteriophage attack as an anti-biofilm strategy.
AB  - Bacteriophages are bacterial viruses. Bacteriophages replicate inside their
      target host whether this is in planktonic or biofilm forms. Here, we describe the
      methods used to control readily formed biofilms using bacteriophages. 

PMID- 24664842
TI  - Photodynamic therapy as a novel antimicrobial strategy against biofilm-based
      nosocomial infections: study protocols.
AB  - Hospital-acquired infections (HAIs), also known as nosocomial infections, are one
      of the most serious health-care issues currently influencing health-care costs.
      Among them, those sustained by microbial biofilm represent a major public health
      concern. Here, we describe the experimental protocols for microbial biofilm
      inactivation relying on antimicrobial photodynamic therapy (APDT) as a new
      strategy for the control of these kinds of infections.

PMID- 24664843
TI  - Capturing air-water interface biofilms for microscopy and molecular analysis.
AB  - Described here is a simple and versatile technique for capturing small samples of
      the thin biofilm that is located at the meniscus of almost every air-water
      interface (AWI), an electrostatically distinct aquatic domain/habitat. The method
      uses a microscope slide (and other supporting surfaces) coated in the lab with a
      collodion membrane, which has a strong affinity for the upper surface of the AWI
      biofilm. The structural integrity of the biofilm is maintained during the capture
      process, and components of the biofilm are effectively separated from the
      subtending liquid. The captured thin biofilm can be analyzed in many ways
      including almost any form of light, electron, and atomic force optics; and
      spatially significant molecular analyses may be performed on the captured biofilm
      or its components.

PMID- 24664844
TI  - Biofilm-growing bacteria involved in the corrosion of concrete wastewater pipes:
      protocols for comparative metagenomic analyses.
AB  - Advances in high-throughput next-generation sequencing (NGS) technology for
      direct sequencing of environmental DNA (i.e., shotgun metagenomics) are
      transforming the field of microbiology. NGS technologies are now regularly being
      applied in comparative metagenomic studies, which provide the data for functional
      annotations, taxonomic comparisons, community profile, and metabolic
      reconstructions. For example, comparative metagenomic analysis of corroded pipes
      unveiled novel insights on the bacterial populations associated with the sulfur
      and nitrogen cycle, which may be directly or indirectly implicated in concrete
      wastewater pipe corrosion. The objective of this chapter is to describe the steps
      involved in the taxonomic and functional analysis of metagenome datasets from
      biofilm involved in microbial-induced concrete corrosion (MICC).

PMID- 24664845
TI  - Culture-independent methods to study subaerial biofilm growing on biodeteriorated
      surfaces of stone cultural heritage and frescoes.
AB  - Actinobacteria, cyanobacteria, algae, and fungi form subaerial biofilm (SAB) that
      can lead to material deterioration on artistic stone and frescoes. In studying
      SAB on cultural heritage surfaces, a general approach is to combine microscopy
      observations and molecular analyses. Sampling of biofilm is performed using
      specific adhesive tape and sampling of SAB and the substrate with sterile
      scalpels and chisels. Biofilm observations are carried out using optical and
      scanning electron microscopy. Specific taxa and EPS in biofilm can be readily
      visualized by fluorochrome staining and subsequent observation using fluorescence
      or confocal laser scanning microscopy. The observation of cross sections
      containing both SAB and the substrate shows if biofilm has developed not only on
      the surface but also underneath. Following nucleic acid extraction, 16S rRNA gene
      sequencing is used to identify bacterial taxa, while 18S rRNA gene and internal
      transcribed spacer (ITS) sequence analysis is used to study eukaryotic groups. In
      this chapter, we illustrate the protocols related to fluorescence in situ
      hybridization (FISH), scanning electron microscopy (SEM), and denaturing gradient
      gel electrophoresis (DGGE).

PMID- 24664846
TI  - Biofilms of thermophilic bacilli isolated from dairy processing plants and
      efficacy of sanitizers.
AB  - In many environments, bacteria can attach to a surface and grow into
      multicellular structures, otherwise known as biofilms. Many systems for studying
      these biofilms in the laboratory are available. To study biofilms of the
      thermophilic bacilli in milk powder-manufacturing plants, standard laboratory
      biofilm techniques need to be adapted. The focus of this chapter is on techniques
      that can be used for growing and analyzing biofilms of thermophilic bacilli that
      are isolated from dairy processing plants. These techniques include laboratory
      methods as well as how to set up a pilot-scale experiment. The laboratory methods
      consist of a microtiter plate assay, which is used for strain selection, and the
      CDC reactor, which is used for testing sanitizers and antimicrobial surfaces. In
      dairy processing, if a new sanitizer or antimicrobial surface appears to be
      promising, it is useful to carry out pilot-scale experiments before introducing
      it to a manufacturing plant. We describe how to set up a pilot-scale experiment
      for testing the efficacy of sanitizers against the thermophilic bacilli. 

PMID- 24664847
TI  - Cardiac iron overload in sickle-cell disease.
AB  - Chronically transfused sickle cell disease (SCD) patients have lower risk of
      myocardial iron overload (MIO) than comparably transfused thalassemia major (TM)
      patients. However, cardioprotection is incomplete. We present the clinical
      characteristics of six patients who have prospectively developed MIO, to identify
      potential risk factors for cardiac iron accumulation. From 2002 to 2011, cardiac,
      hepatic, and pancreatic iron overload were assessed by R2 and R2 * magnetic
      resonance imaging techniques in 201 chronic transfused SCD patients as part of
      their clinical care. At the time, they developed MIO, five of six patients had
      been on chronic transfusion for more than 11 years; only one was on exchange
      transfusion. The time to MIO was correlated with reticulocyte and hemoglobin S
      percentages. All patients had qualitatively poor chelation compliance (<50%). All
      patients had serum ferritin levels >4600 ng/ml and liver iron concentration >22
      mg/g. Pancreatic R2 * was >100 Hz in every patient studied (5/6). Cardiac iron
      rose proportionally to pancreas R2 *, with all patients having pancreas R2 *>100
      Hz when cardiac iron was present. MIO had a threshold relationship with liver
      iron that was higher than observed in TM patients. In conclusion, MIO occurs in a
      small percentage of chronically transfused SCD patients and is only associated
      with exceptionally poor control of total body iron stores. Duration of chronic
      transfusion is clearly important but other factors, such as levels of effective
      erythropoiesis, appear to contribute to cardiac risk. Pancreas R2 * can serve as
      a valuable screening tool for cardiac iron in SCD patients.

PMID- 24664849
TI  - The hepatitis B vaccine originally jointly developed by China and the US is safe
      and effective.

PMID- 24664851
TI  - Microsphere-based intracellular sensing of caspase-3/7 in apoptotic living cells.
AB  - A novel multifunctional probe to monitor intracellular enzymatic activity in
      living cells is successfully developed. Their use as accurate intracellular
      sensors by conjugation of an internal control (that gives an extra feature to
      both evaluate cellular-uptake efficiency and track probes over time) is reported.
      In particular, a specific application of these multifunctional microspheres as
      sensors of caspase-3/7 to monitor apoptosis by flow cytometry is described. The
      preparation of these devices together with a kinetic study towards caspase-3 and
      caspase-7 and their evaluation as flow cytometry probe in apoptotic living cells
      are reported. 

PMID- 24664850
TI  - Cytoplasmic dynein: a key player in neurodegenerative and neurodevelopmental
      diseases.
AB  - Cytoplasmic dynein is the most important molecular motor driving the movement of
      a wide range of cargoes towards the minus ends of microtubules. As a molecular
      motor protein, dynein performs a variety of basic cellular functions including
      organelle transport and centrosome assembly. In the nervous system, dynein has
      been demonstrated to be responsible for axonal retrograde transport. Many studies
      have revealed direct or indirect evidence of dynein in neurodegenerative diseases
      such as amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Alzheimer's
      disease, Parkinson's disease and Huntington's disease. Among them, a number of
      mutant proteins involved in various neurodegenerative diseases interact with
      dynein. Axonal transport disruption is presented as a common feature occurring in
      neurodegenerative diseases. Dynein heavy chain mutant mice also show features of
      neurodegenerative diseases. Moreover, defects of dynein-dependent processes such
      as autophagy or clearance of aggregation-prone proteins are found in most of
      these diseases. Lines of evidence have also shown that dynein is associated with
      neurodevelopmental diseases. In this review, we focus on dynein involvement in
      different neurological diseases and discuss potential underlying mechanisms. 

PMID- 24664852
TI  - Context effects as auditory contrast.
AB  - Three experiments are reported that collectively show that listeners perceive
      speech sounds as contrasting auditorily with neighboring sounds. Experiment 1
      replicates the well-established finding that listeners categorize more of a [d-g]
      continuum as [g] after [l] than after [r]. Experiments 2 and 3 show that
      listeners discriminate stimuli in which the energy concentrations differ in
      frequency between the spectra of neighboring sounds better than those in which
      they do not differ. In Experiment 2, [alga-arda] pairs, in which the energy
      concentrations in the liquid-stop sequences are H(igh) L(ow)-LH, were more
      discriminable than [alda-arga] pairs, in which they are HH-LL. In Experiment 3,
      [da] and [ga] syllables were more easily discriminated when they were preceded by
      lower and higher pure tones, respectively-that is, tones that differed from the
      stops' higher and lower F3 onset frequencies-than when they were preceded by H
      and L pure tones with similar frequencies. These discrimination results show that
      contrast with the target's context exaggerates its perceived value when energy
      concentrations differ in frequency between the target's spectrum and its
      context's spectrum. Because contrast with its context does more that merely shift
      the criterion for categorizing the target, it cannot be produced by neural
      adaptation. The finding that nonspeech contexts exaggerate the perceived values
      of speech targets also rules out compensation for coarticulation by showing that
      their values depend on the proximal auditory qualities evoked by the stimuli's
      acoustic properties, rather than the distal articulatory gestures. 

PMID- 24664853
TI  - Rewarding distractor context versus rewarding target location: a commentary on
      Tseng and Lleras (2013).
AB  - The influence of reward on cognitive processes including visual perception,
      spatial attention, and perceptual learning has become an increasingly important
      field of study in recent years. For example, Tseng and Lleras (Attention,
      Perception, & Psychophysics, 75(2), 287-298, 2013) investigated whether reward
      has an effect on implicit learning of target-distractor arrangements in visual
      search-that is, contextual cueing (Chun & Jiang Cognitive Psychology, 36(1), 28
      71, 1998). They found that reward expedited the development of the cueing effect
      that is, the reaction time difference between repeated and nonrepeated displays.
      However, their analysis did not account for potential effects of reward on the
      learning of individual target locations-that is, probability cueing (Jiang,
      Swallow, & Rosenbaum Journal of Experimental Psychology. Human Perception and
      Performance, 39, 285-297, 2013). The present study was a replication of Tseng and
      Lleras (Attention, Perception, & Psychophysics, 75(2), 287-298, 2013) that took
      into account reward effects on configural and locational learning, as well. We
      found that reward led to performance gains even in baseline ("new") displays,
      which contained only repeated target, but not distractor, locations. Furthermore,
      contextual cueing was smaller, and not larger, in high- than in low-reward
      trials. We concluded that reward modulates probability, and not contextual,
      cueing, and that this mechanism can account for the findings of Tseng and Lleras.

PMID- 24664854
TI  - Emotion recognition (sometimes) depends on horizontal orientations.
AB  - Face recognition depends critically on horizontal orientations (Goffaux & Dakin,
      Frontiers in Psychology, 1(143), 1-14, 2010): Face images that lack horizontal
      features are harder to recognize than those that have this information preserved.
      We asked whether facial emotional recognition also exhibits this dependency by
      asking observers to categorize orientation-filtered happy and sad expressions.
      Furthermore, we aimed to dissociate image-based orientation energy from object
      based orientation by rotating images 90 deg in the picture plane. In our first
      experiment, we showed that the perception of emotional expression does depend on
      horizontal orientations, and that object-based orientation constrained
      performance more than image-based orientation did. In Experiment 2, we showed
      that mouth openness (i.e., open vs. closed mouths) also influenced the emotion
      dependent reliance on horizontal information. Finally, we describe a simple
      computational analysis that demonstrates that the impact of mouth openness was
      not predicted by variation in the distribution of orientation energy across
      horizontal and vertical orientation bands. Overall, our results suggest that
      emotion recognition largely does depend on horizontal information defined
      relative to the face, but that this bias is modulated by multiple factors that
      introduce variation in appearance across and within distinct emotions.

PMID- 24664855
TI  - Healthcare databases in Europe for studying medicine use and safety during
      pregnancy.
AB  - PURPOSE: The aim of this study was to describe a number of electronic healthcare
      databases in Europe in terms of the population covered, the source of the data
      captured and the availability of data on key variables required for evaluating
      medicine use and medicine safety during pregnancy. METHODS: A sample of
      electronic healthcare databases that captured pregnancies and prescription data
      was selected on the basis of contacts within the EUROCAT network. For each
      participating database, a database inventory was completed. RESULTS: Eight
      databases were included, and the total population covered was 25 million. All
      databases recorded live births, seven captured stillbirths and five had full data
      available on spontaneous pregnancy losses and induced terminations. In six
      databases, data were usually available to determine the date of the woman's last
      menstrual period, whereas in the remainder, algorithms were needed to establish a
      best estimate for at least some pregnancies. In seven databases, it was possible
      to use data recorded in the databases to identify pregnancies where the offspring
      had a congenital anomaly. Information on confounding variables was more commonly
      available in databases capturing data recorded by primary-care practitioners. All
      databases captured maternal co-prescribing and a measure of socioeconomic status.
      CONCLUSION: This study suggests that within Europe, electronic healthcare
      databases may be valuable sources of data for evaluating medicine use and safety
      during pregnancy. The suitability of a particular database, however, will depend
      on the research question, the type of medicine to be evaluated, the prevalence of
      its use and any adverse outcomes of interest. (c) 2014 The Authors.
      Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

PMID- 24664856
TI  - Genetic counseling practice in next generation sequencing research: implications
      for the ethical oversight of the informed consent process.
AB  - The potential for next generation sequencing research (NGS) to generate
      individual genetic results could have implications for the informed consent
      process and the provision of genetic counseling. We undertook a content analysis
      of informed consent templates and guidelines produced by Canadian institutional
      review boards, purposively sampling documents used by researchers to obtain
      consent from participants in genetics studies. Our goal was to examine the extent
      to which the informed consent documents addressed genetic counseling and the
      return of individual genetic results. Our analysis reveals that the majority of
      informed consent documents did not mention genetic counseling while several did
      not mention the return of results. We found differences in the ways in which
      documents addressed availability of counseling, eligibility criteria for referral
      to a genetic counselor, genetic counselor involvement, provision of services to
      family members of participants and incidental findings. From an ethical
      standpoint, consent documents should provide appropriate information so that
      participants may make an informed decision about their participation in research.
      The need to ensure adequate counseling for study populations in an NGS research
      context will necessarily involve adapting values that underlie care in genetic
      counseling practice. If the interests of research participants are to be truly
      promoted, the drafting and review of informed consent documents should give
      proper due to genetic counseling. 

PMID- 24664857
TI  - Motivation to pursue genetic testing in individuals with a personal or family
      history of cardiac events or sudden cardiac death.
AB  - Genetic testing is becoming increasingly available for cardiac channelopathies,
      such as long QT syndrome and Brugada syndrome, which can lead to sudden cardiac
      death. Test results can be used to shape an individual's medical management and
      to identify at-risk family members. In our qualitative study, all participants
      had a personal or family history of a diagnosed cardiac arrhythmia syndrome or
      sudden cardiac death. Open-ended interviews were conducted individually and in
      focus groups. Interviews were audio recorded, transcribed verbatim, and analyzed
      using a qualitative grounded-theory approach. Of 50 participants, 37 described
      their motivations for pursuing genetic testing for long QT syndrome or another
      cardiac channelopathy. Participants' motivations included: to find an explanation
      for a family member's sudden death, to relieve uncertainty regarding a diagnosis,
      to guide future medical management, to allay concern about children or other
      family members, and to comply with recommendations of physicians or family
      members. Perceived reasons not to pursue genetic testing included denial, fear,
      and lack of information. The genetic counseling and informed consent process can
      be enhanced by understanding and addressing an individual's internal and external
      motivations either for or against pursuing genetic testing.

PMID- 24664858
TI  - Enhancing physical performance in male volleyball players with a caffeine
      containing energy drink.
AB  - There are no scientific data about the effects of caffeine intake on volleyball
      performance. The aim of this study was to investigate the effect of a caffeine
      containing energy drink to enhance physical performance in male volleyball
      players. A double-blind, placebo-controlled, randomized experimental design was
      used. In 2 different sessions separated by 1 wk, 15 college volleyball players
      ingested 3 mg of caffeine per kg of body mass in the form of an energy drink or
      the same drink without caffeine (placebo). After 60 min, participants performed
      volleyball-specific tests: standing spike test, maximal squat jump (SJ), maximal
      countermovement jump (CMJ), 15-s rebound jump test (15RJ), and agility T-test.
      Later, a simulated volleyball match was played and recorded. In comparison with
      the placebo drink, the ingestion of the caffeinated energy drink increased ball
      velocity in the spike test (73 +/- 9 vs 75 +/- 10 km/h, P < .05) and the mean
      jump height in SJ (31.1 +/- 4.3 vs 32.7 +/- 4.2 cm, P < .05), CMJ (35.9 +/- 4.6
      vs 37.7 +/- 4.4 cm, P < .05), and 15RJ (29.0 +/- 4.0 vs 30.5 +/- 4.6 cm, P <
      .05). The time to complete the agility test was significantly reduced with the
      caffeinated energy drink (10.8 +/- 0.7 vs 10.3 +/- 0.4 s, P < .05). In addition,
      players performed successful volleyball actions more frequently (24.6% +/- 14.3%
      vs 34.3% +/- 16.5%, P < .05) with the ingestion of the caffeinated energy drink
      than with the placebo drink during the simulated game. A caffeine-containing
      energy drink, with a dose equivalent to 3 mg of caffeine per kg body mass, might
      be an effective ergogenic aid to improve physical performance and accuracy in
      male volleyball players. 

PMID- 24664859
TI  - Oxidative DNA damage as a potential early biomarker of Helicobacter pylori
      associated carcinogenesis.
AB  - Helicobacter pylori infection is an established risk factor for gastritis,
      gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been
      associated with oxidative DNA damage of gastric mucosa but their combined role in
      the development of gastric cancer is still unknown. Here we compare the combined
      expression of cagA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in normal, gastritis
      and gastric cancer tissues. Two hundred gastric biopsies from patients with
      dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from
      non-dyspeptic individuals (controls) were included in this study and 8-OHdG was
      detected by immunohistochemistry (IHC). Histological features and the presence of
      H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and
      alcian blue-periodic acid-Schiff +/- diastase (AB-PAS +/- D) staining. DNA was
      extracted from tissues and polymerase chain reaction (PCR) performed to determine
      the presence of ureaseA and cagA genes of H. pylori. The results showed the
      presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic
      patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA
      gene and high expression of 8-OHdG was highly correlated with severe gastric
      inflammation and gastric cancer particularly, in cases with infiltration of
      chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2
      %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric
      cancer (95 %, 95.4 %) (p <= 0.01). In conclusion, H. Pylori cagA gene expression
      and the detection of 8-OHdG adducts in gastric epithelium can serve as potential
      early biomarkers of H. Pylori-associated gastric carcinogenesis.

PMID- 24664861
TI  - Photodynamics of [26]- and [28]hexaphyrin-bodipy hybrids.
AB  - A set of hybrids having gradual variation in distances between hexaphyrin and
      bodipy moieties, given by uses of phenylene, biphenylene, and triphenyelene
      bridges was prepared. Efficient PET processes from bodipy (donor) to [26]- or
      [28]hexaphyrin (acceptor) were successfully observed, where the PET speed was
      controlled by intramolecular distances between the donor and the acceptor. UV
      irradiation at 515 nm raised a band corresponding to the bodipy absorption. As
      the time delayed, the bodipy bands decreased and new absorption bands at 615 and
      580 nm corresponding to respective absorption bands of [28]- and [26]-hybrids
      gradually appeared. Whereas the femtosecond transient absorption spectra of
      [28]/[26]-hybrids having terphenylene bridges completely showed energy transfers
      from bodipy to hexaphyrin, irradiation of the hybrids using 615 and 580 nm pulses
      did not induce opposite ways of the PET process. On the basis of enlarged center
      to-center-distances of [26]-hybrids than those of [28]-hybrids, the set of [26]
      hybrids resulted in slow decay/rise processes. PET parameters obtained with the
      experiments were fairly consistent with the PET parameters calculated. 

PMID- 24664860
TI  - Physiological and behavioral signatures of reflective exploratory choice.
AB  - Physiological arousal, a marker of emotional response, has been demonstrated to
      accompany human decision making under uncertainty. Anticipatory emotions have
      been portrayed as basic and rapid evaluations of chosen actions. Instead, could
      these arousal signals stem from a "cognitive" assessment of value that utilizes
      the full environment structure, as opposed to merely signaling a coarse,
      reflexive assessment of the possible consequences of choices? Combining an
      exploration-exploitation task, computational modeling, and skin conductance
      measurements, we find that physiological arousal manifests a reflective
      assessment of the benefit of the chosen action, mirroring observed behavior.
      Consistent with the level of computational sophistication evident in these
      signals, a follow-up experiment demonstrates that anticipatory arousal is
      modulated by current environment volatility, in accordance with the predictions
      of our computational account. Finally, we examine the cognitive costs of the
      exploratory choice behavior these arousal signals accompany by manipulating
      concurrent cognitive demand. Taken together, these results demonstrate that the
      arousal that accompanies choice under uncertainty arises from a more reflective
      and "cognitive" assessment of the chosen action's consequences than has been
      revealed previously.

PMID- 24664862
TI  - The Nozoe Autograph Books: why sign them? Why publish them? Why read them? Why
      treasure them? Personal and professional reflections.

PMID- 24664863
TI  - Modeling developmental changes in yo-yo intermittent recovery test level 1 in
      elite pubertal soccer players.
AB  - PURPOSE: To model the development of soccer-specific aerobic performance,
      assessed by the Yo-Yo Intermittent Recovery Test Level 1 in 162 elite pubertal
      soccer players, age 11-14 y at baseline. METHODS: Longitudinal multilevel
      modeling analyses comprised predictors related to growth (chronological age, body
      size [height and weight] and composition [fat mass, fat-free mass]), and motor
      coordination [3 KOrperkoordination Test fur Kinder subtests: jumping sideways,
      moving sideways, backward balancing] and estimated biological-maturation groups
      (earliest [<percentile 33] and latest maturers [>percentile 66]). RESULTS: The
      best-fitting model on soccer-specific aerobic performance could be expressed as 
      3639.76 + 369.86 * age + 21.38 * age2 + 9.12 * height - 29.04 * fat mass + 0.06 *
      backward balance. Maturity groups had a negligible effect on soccer-specific
      aerobic performance (-45.32 +/- 66.28; P > .05). CONCLUSION: The current study
      showed that the development of aerobic performance in elite youth soccer is
      related to growth and muscularity and emphasized the importance of motor
      coordination in the talent-identification and -development process. Note that
      biological maturation was excluded from the model, which might endorse the
      homogeneity in estimated biological-maturation status in the current elite
      pubertal soccer sample.

PMID- 24664864
TI  - Widespread rapid reductions in body size of adult salamanders in response to
      climate change.
AB  - Reduction in body size is a major response to climate change, yet evidence in
      globally imperiled amphibians is lacking. Shifts in average population body size
      could indicate either plasticity in the growth response to changing climates
      through changes in allocation and energetics, or through selection for decreased
      size where energy is limiting. We compared historic and contemporary size
      measurements in 15 Plethodon species from 102 populations (9450 individuals) and
      found that six species exhibited significant reductions in body size over 55
      years. Biophysical models, accounting for actual changes in moisture and air
      temperature over that period, showed a 7.1-7.9% increase in metabolic expenditure
      at three latitudes but showed no change in annual duration of activity. Reduced
      size was greatest at southern latitudes in regions experiencing the greatest
      drying and warming. Our results are consistent with a plastic response of body
      size to climate change through reductions in body size as mediated through
      increased metabolism. These rapid reductions in body size over the past few
      decades have significance for the susceptibility of amphibians to environmental
      change, and relevance for whether adaptation can keep pace with climate change in
      the future. 

PMID- 24664865
TI  - The comparative gastrointestinal morphology of five species of muroid rodents
      found in Saudi Arabia.
AB  - Meriones rex (King jird), Meriones libycus (Libyan jird), Acomys dimidiatus
      (Eastern spiny mouse), Acomys cahirinus (Egyptian spiny mouse), and Dipodillus
      dasyurus (Wagner's dipodil) are five species of small rodents of the superfamily
      Muroidea with distributions in Eastern Africa, Egypt, and the desert regions of
      the Arabian Peninsula. Water is scarce in these regions and may result in
      relatively low-digestible food. The aim of the present study is to describe and
      compare the gastrointestinal tract morphology and morphometry of these five
      species in order to elucidate whether morphology is influenced by phylogeny or
      dietary preference. Each segment of the gastrointestinal tract of each species
      was macroscopically examined and the length and basal surface area of each
      segment was measured. Standard histologic procedures were performed to determine
      a surface enlargement factor to determine the mucosal luminal surface area. A
      unilocular-hemiglandular stomach was observed in all the species examined. The
      caeca of all the species were long and arranged into a loose spiral toward the
      caecal tip with the ileocaecal and caeco-colic openings positioned close
      together. Two rows of oblique folds could be observed in the proximal colon of
      all species except in D. dasyurus which had longitudinal folds. Morphometric
      analysis showed the largest stomach in A. cahirinus and the largest caecum and
      colon in M. libycus. All the species can be grouped in the family Muridae in two
      subfamilies and similarities were observed including the hemiglandular stomach
      and relatively large caecum. It could be concluded that phylogeny plays an
      important role in determining gastrointestinal morphology while diet plays a
      subordinate role in the desert rodents in the present study.

PMID- 24664868
TI  - Deficits in muscle mass, muscle density, and modified associations with fat in
      rheumatoid arthritis.
AB  - OBJECTIVE: To quantify muscle outcomes, independent of fat mass, in rheumatoid
      arthritis (RA) patients compared to healthy controls. METHODS: Quantitative
      computed tomography scans measured calf muscle and fat cross-sectional area (CSA)
      and muscle density (an index of intramuscular adipose tissue), and isometric
      dynamometry was used to measure ankle muscle strength in 50 participants with RA
      ages 18-70 years and 500 healthy controls. Multivariable linear regression models
      assessed muscle deficits in RA after adjusting for group differences in adiposity
      and assessing for an altered muscle-fat association. Associations between RA
      disease characteristics and fat-adjusted muscle outcomes were also assessed.
      RESULTS: Compared to controls, RA subjects had significantly greater body mass
      index (BMI) and fat area, and lower muscle area, muscle density, and muscle
      strength (P < 0.001 for all). Strength deficits were eliminated with adjustment
      for the smaller muscle area. The magnitude of muscle deficits, relative to
      controls, was significantly greater (P < 0.03 for interaction) in participants
      with lower fat area and BMI. Among those in the lower tertiles of adiposity, RA
      subjects demonstrated more significant deficits compared to controls with similar
      adiposity. In contrast, among those in the highest tertile for adiposity, RA was
      not associated with muscle deficits. Among RA, greater Sharp/van der Heijde
      scores were associated with lower muscle CSA and muscle density. Greater disease
      activity and disability were associated with low muscle density. CONCLUSION:
      Deficits in muscle area and muscle density are present in RA patients compared to
      controls and are most pronounced in subjects with low fat mass. Greater joint
      destruction is associated with greater muscle deficits.

PMID- 24664866
TI  - Oxidative stress in Alzheimer's disease.
AB  - Oxidative stress plays a significant role in the pathogenesis of Alzheimer's
      disease (AD), a devastating disease of the elderly. The brain is more vulnerable
      than other organs to oxidative stress, and most of the components of neurons
      (lipids, proteins, and nucleic acids) can be oxidized in AD due to mitochondrial
      dysfunction, increased metal levels, inflammation, and beta-amyloid (Abeta)
      peptides. Oxidative stress participates in the development of AD by promoting
      Abeta deposition, tau hyperphosphorylation, and the subsequent loss of synapses
      and neurons. The relationship between oxidative stress and AD suggests that
      oxidative stress is an essential part of the pathological process, and
      antioxidants may be useful for AD treatment.

PMID- 24664869
TI  - Charge-transfer complex crystal based on extended-pi-conjugated acceptor and
      sulfur-bridged annulene: charge-transfer interaction and remarkable high
      ambipolar transport characteristics.
AB  - A single crystal of a novel mixed-stack donor-acceptor complex formed by a
      tetracyanoquinodimethane derivative with an extended pi-conjugated system and a
      sulfur-bridged annulene displays the highest ambipolar transport behavior among
      donor-acceptor complexes reported with electron and hole mobilities reaching up
      to 0.24 and 0.77 cm(2) V(-1) s(-1) , respectively. 

PMID- 24664871
TI  - Sorting out meiosis.

PMID- 24664870
TI  - Nemo-like kinase regulates postnatal skeletal homeostasis.
AB  - Nemo-like kinase (Nlk) is related to the mitogen-activated protein (MAP) kinases
      and known to regulate signaling pathways involved in osteoblastogenesis. In vitro
      Nlk suppresses osteoblastogenesis, but the consequences of the Nlk inactivation
      in the skeleton in vivo are unknown. To study the function of Nlk, Nlk(loxP/loxP)
      mice, where the Nlk exon2 is flanked by lox(P) sequences, were mated with mice
      expressing the Cre recombinase under the control of the paired-related homeobox
      gene 1 (Prx1) enhancer (Prx1-Cre), the Osterix (Osx-Cre) or the osteocalcin/bone
      gamma carboxyglutamate protein (Bglap-Cre) promoter. Prx1-Cre;Nlk(Delta/Delta)
      mice did not exhibit a skeletal phenotype except for a modest increase in
      trabecular number and connectivity observed only in 3-month-old male mice. Osx
      Cre;Nlk(Delta/Delta) male and female mice exhibited an increase in trabecular
      bone volume secondary to an increased trabecular number at 3 months of age. Bone
      histomorphometry revealed a decrease in osteoclast number and eroded surface in
      male mice, and decreased osteoblast number and function in female mice.
      Expression of osteoprotegerin mRNA was increased in calvarial extracts,
      explaining the decreased osteoclast and osteoblast number. The conditional
      deletion of Nlk in mature osteoblasts (Bglap-Cre;Nlk(Delta/Delta) ) resulted in
      no skeletal phenotype in 1- to 6-month-old male or female mice. In conclusion,
      when expressed in undifferentiated osteoblasts, Nlk is a negative regulator of
      skeletal homeostasis possibly by targeting signals that regulate
      osteoclastogenesis and bone resorption.

PMID- 24664867
TI  - Environmental factors in the development and progression of late-onset
      Alzheimer's disease.
AB  - Late-onset Alzheimer's disease (LOAD) is an age-related neurodegenerative
      disorder characterized by gradual loss of synapses and neurons, but its
      pathogenesis remains to be clarified. Neurons live in an environment constituted
      by neurons themselves and glial cells. In this review, we propose that the
      neuronal degeneration in the AD brain is partially caused by diverse
      environmental factors. We first discuss various environmental stresses and the
      corresponding responses at different levels. Then we propose some mechanisms
      underlying the specific pathological changes, in particular, hypothalamic
      pituitary adrenal axis dysfunction at the systemic level; cerebrovascular
      dysfunction, metal toxicity, glial activation, and Abeta toxicity at the
      intercellular level; and kinase-phosphatase imbalance and epigenetic modification
      at the intracellular level. Finally, we discuss the possibility of developing new
      strategies for the prevention and treatment of LOAD from the perspective of
      environmental stress. We conclude that environmental factors play a significant
      role in the development of LOAD through multiple pathological mechanisms.

PMID- 24664874
TI  - Balancing the rate of cluster growth and etching for gram-scale synthesis of
      thiolate-protected Au(25) nanoclusters with atomic precision.
AB  - We report a NaOH-mediated NaBH4 reduction method for the synthesis of mono-, bi-,
      and tri-thiolate-protected Au25 nanoclusters (NCs) with precise control of both
      the Au core and thiolate ligand surface. The key strategy is to use NaOH to tune
      the formation kinetics of Au NCs, i.e., reduce the reduction ability of NaBH4 and
      accelerate the etching ability of free thiolate ligands, leading to a well
      balanced reversible reaction for rapid formation of thermodynamically favorable
      Au25 NCs. This protocol is facile, rapid (<=3 h), versatile (applicable for
      various thiolate ligands), and highly scalable (>1 g Au NCs). In addition, bi-
      and tri-thiolate-protected Au25 NCs with adjustable ratios of hetero-thiolate
      ligands were easily obtained. Such ligand precision in molecular ratios, spatial
      distribution and uniformity resulted in richly diverse surface landscapes on the
      Au NCs consisting of multiple functional groups such as carboxyl, amine, and
      hydroxy. Analysis based on NMR spectroscopy revealed that the hetero-ligands on
      the NCs are well distributed with no ligand segregation. The unprecedented
      synthesis of multi-thiolate-protected Au25 NCs may further promote the practical
      applications of functional metal NCs. 

PMID- 24664872
TI  - Baseline predictors of efavirenz-containing antiretroviral regimen adverse
      experiences.
AB  - PURPOSE: We aimed to identify modifiable, routinely available patient
      characteristics associated with adverse experiences potentially attributable to
      efavirenz-based regimens in patients in Botswana. METHODS: HIV-infected treatment
      naive individuals starting a standard antiretroviral regimen including two
      nucleoside analog reverse transcriptase inhibitors and efavirenz in Botswana were
      enrolled in a prospective cohort. Adverse experiences were measured at 1 and 6
      months using the efavirenz checklist, a 35-item instrument developed by the AIDS
      Clinical Trials Group. RESULTS: We enrolled 232 patients from 11 March 2010 to 17
      March 2011. One hundred ninety-six were included in the month 1 analyses. Of the
      196 included in the month 1 analyses, 157 (80%) completed the 6-month follow-up.
      Median efavirenz checklist score was 6 (interquartile range (IQR): 2-15) at month
      1 and 1 (IQR: 0-5) at month 6. The median change in efavirenz checklist score
      from month 1-6 was -4 (IQR: -11 to -1), representing an improvement. Depressive
      symptoms, low CD4 count and less alcohol use were associated with improvement in
      adverse experiences over time. Low weight was associated with increased extent of
      adverse experiences at month 1 and 6. There was no confounding or effect
      modification. CONCLUSIONS: Clinicians may want to consider more intensive and
      tailored adverse experience education and management in patients based on
      depressive symptoms, CD4 count, and weight. Further assessment of the mechanism
      of the effect of alcohol use on adverse experiences, including analysis of CYP2B6
      genotype and plasma efavirenz concentrations, is warranted.

PMID- 24664873
TI  - A three generation X-linked family with Kabuki syndrome phenotype and a
      frameshift mutation in KDM6A.
AB  - Kabuki syndrome is a rare malformation syndrome characterized by a typical facial
      appearance, skeletal anomalies, cardiac malformation, and mild to moderate
      intellectual disability. In 55-80% of patients with Kabuki syndrome, a mutation
      in MLL2 is identified. Recently, eight patients with Kabuki syndrome and a
      mutation in KDM6A were described. In this report, we describe two brothers with a
      mutation in KDM6A inherited from their mother and maternal grandmother. The two
      boys have Kabuki-like phenotypes whereas the mother and grandmother present with
      attenuated phenotypes. This family represents the first instance of hereditary X
      linked Kabuki syndrome. We present a short literature review of the patients
      described with a mutation in KDM6A.

PMID- 24664875
TI  - Views on human papillomavirus vaccination: a mixed-methods study of urban youth.
AB  - While the human papillomavirus (HPV) vaccine has potential to protect against the
      majority of HPV-associated cancers, vaccination rates in the United States remain
      low. Racial/ethnic and economic disparities exist for HPV vaccination completion
      rates. We conducted a mixed-methods study using the theory of planned behavior
      framework to explore attitudes and beliefs about HPV vaccination among urban,
      economically disadvantaged adolescents. Fifty adolescents aged 14-18 years were
      recruited from community-based organizations to complete a written survey and
      participate in a focus group. The mean age was 15.5 +/- 1.3 years; 98 % were
      African American or mixed race; 64 % were female; 52 % reported previous sexual
      intercourse; 40 % reported receipt of >=1 HPV vaccine dose. The knowledge deficit
      about the HPV vaccine was profound and seemed slightly greater among males.
      Mothers, fathers and grandmothers were mentioned as important referents for HPV
      vaccination, but peers and romantic partners were not. Common barriers to
      vaccination were lack of awareness, anticipated side effects (i.e., pain), and
      concerns about vaccine safety. Characteristics associated with >=1 vaccine dose
      were: having heard of the HPV vaccine versus not (65 vs. 20 %, p = 0.002) and
      agreeing with the statement "Most people I know would think HPV vaccine is good
      for your health" versus not (67 vs. 27 %, p = 0.007). Our work indicates a
      profound lack of awareness about HPV vaccination as well as the important
      influence of parents among urban, economically-disadvantaged youth. Awareness of
      these attitudes and beliefs can assist providers and health officials by
      informing specific interventions to increase vaccine uptake.

PMID- 24664876
TI  - Diagnostic Exome Sequencing and Tailored Bioinformatics of the Parents of a
      Deceased Child with Cobalamin Deficiency Suggests Digenic Inheritance of the MTR
      and LMBRD1 Genes.
AB  - Disorders of cobalamin deficiency are a heterogeneous group of disorders with at
      least 19 autosomal recessive-associated genes. Familial samples of an infant who
      died due to presumed cobalamin deficiency were referred for clinical exome
      sequencing. The patient died before obtaining a blood sample or skin biopsy,
      autopsy was declined, and DNA yielded from the newborn screening blood spot was
      insufficient for diagnostic testing. Whole-exome sequencing of the mother,
      father, and unaffected sister and tailored bioinformatics analysis was applied to
      search for mutations in underlying disorders with recessive inheritance. This
      approach identified alterations within two genes, each of which was carried by
      one parent. The mother carried a missense alteration in the MTR gene (c.3518C>T;
      p.P1173L) which was absent in the father and the sister. The father carried a
      translational frameshift alteration in the LMBRD1 gene (c.1056delG; p.L352Lfs*18)
      which was absent in the mother and present in the heterozygous state in the
      sister. These mutations in the MTR (MIM# 156570) and LMBRD1 (MIM# 612625) genes
      have been described in patients with disorders of cobalamin metabolism
      complementation groups cblG and cblF, respectively. The child's clinical
      presentation and biochemical results demonstrated overlap with both cblG and
      cblF. Sanger sequencing using DNA from the infant's blood spot confirmed the
      inheritance of the two alterations in compound heterozygous form. We present the
      first example of exome sequencing leading to a diagnosis in the absence of the
      affected patient. Furthermore, the data support the possibility for potential
      digenic inheritance associated with cobalamin deficiency. 

PMID- 24664877
TI  - Neurogenic bladder dysfunction presenting as urinary retention in neuronopathic
      Gaucher disease.
AB  - Neuronopathic Gaucher disease can present as a continuum of clinical findings,
      including somatic symptoms of anemia, thrombocytopenia, hepatosplenomegaly, and
      bone disease as well as neurologic sequelae. There is a spectrum of neurologic
      symptoms ranging from oculomotor apraxia to severe convulsions. The
      heterozygosity of phenotypes makes it difficult to predict the disease course. We
      describe an 8-year-old male with neuronopathic type III Gaucher disease who
      developed bladder dysfunction and was unable to completely void. He also
      presented with hypertension and acute renal insufficiency, most likely secondary
      to urinary retention. A complete evaluation was done for causes of urinary
      retention and bladder dysfunction. A renal bladder ultrasound demonstrated marked
      hydroureteronephrosis. There was no clinical evidence of infection and cystoscopy
      revealed no anatomic obstruction. In addition, MRI showed no spinal
      abnormalities. His bladder dysfunction was managed operatively by creating a
      catheterizable stoma, using his appendix, to empty his bladder, and surgical
      findings were consistent with neurogenic bladder. He continues to be managed for
      his Gaucher disease and neurogenic bladder by genetics, nephrology and urology.
      This is the first clinical report of neurogenic bladder dysfunction in
      neuronopathic Gaucher disease. 

PMID- 24664879
TI  - Synthesis and characterization of a triphenyl-substituted radical and an
      unprecedented formation of a carbene-functionalized quinodimethane.
AB  - The trichlorosilylcarbene monoradical (Cy-cAAC .)SiCl3 (1) was directly converted
      to (Cy-cAAC .)SiPh3 (2) by substitution of the three chlorine atoms with phenyl
      groups without affecting the radical center adjacent to the silicon atom. In
      addition to the structure determination, compound 2 was studied by EPR
      spectroscopy and DFT calculations. The three hyperfine lines in the EPR spectrum
      of 2 are due to the coupling with (14)N nucleus. Functionalized 1,4
      quinodimethane Me2-cAAC=C6H4=CPh2 (7) was isolated, whereas carbon analogue of
      radical 2 was targeted. Cyclic voltammogram of 7 indicated that a stable radical
      anion 7  .-, as well as a radical-cation 7  .+, can be prepared. Theoretical
      calculations showed that one-electron ionization energy and electron affinity of
      7 are 5.1 and 0.7 eV mol(-1), respectively.

PMID- 24664878
TI  - Changing patterns of HIV epidemic in 30 years in East Asia.
AB  - The HIV epidemic in East Asia started relatively late compared to the rest of the
      world. All countries or areas, except for North Korea, had reported HIV and AIDS
      cases, with China being the major contributor to the epidemic. Though initially
      driven by injecting drug use in China, East Asia did not experience an explosive
      spread. Strong commitment in China and early harm reduction programs in Taiwan
      managed to reduce transmission substantially among injecting drug users. In
      contrast to China and Taiwan, injection drug use has accounted just a little, if
      not at all, for the spread of HIV in other East Asian counties. However,
      following a global trend, sexual contact has become a major route of infection
      across the region. While much progress has been achieved in this region, with the
      epidemic among other key populations relatively stable, the emerging epidemic
      through sex between men is a growing concern. Recent estimates suggest that HIV
      prevalence among men who have sex with men (MSM) has reached 6.3 % in China, 7.5
      % in Mongolia, and ranges between 8.1 %-10.7 % in Taiwan and between 2.7 %- 6.5 %
      in South Korea. In Japan, 74 % of male HIV cases were among MSM in 2012, while
      Hong Kong has witnessed a sharp increase of HIV cases among MSM since 2004. There
      is urgent need to address issues of discrimination and stigma toward
      homosexuality, and to strengthen the strategies to reach and care for this
      population.

PMID- 24664880
TI  - Zipf's word frequency law in natural language: a critical review and future
      directions.
AB  - The frequency distribution of words has been a key object of study in statistical
      linguistics for the past 70 years. This distribution approximately follows a
      simple mathematical form known as Zipf's law. This article first shows that human
      language has a highly complex, reliable structure in the frequency distribution
      over and above this classic law, although prior data visualization methods have
      obscured this fact. A number of empirical phenomena related to word frequencies
      are then reviewed. These facts are chosen to be informative about the mechanisms
      giving rise to Zipf's law and are then used to evaluate many of the theoretical
      explanations of Zipf's law in language. No prior account straightforwardly
      explains all the basic facts or is supported with independent evaluation of its
      underlying assumptions. To make progress at understanding why language obeys
      Zipf's law, studies must seek evidence beyond the law itself, testing assumptions
      and evaluating novel predictions with new, independent data.

PMID- 24664881
TI  - Holistic processing improves change detection but impairs change identification.
AB  - It has been just over a century since Gestalt psychologists described the factors
      that contribute to the holistic processing of visually presented stimuli. Recent
      research indicates that holistic processing may come at a cost; specifically, the
      perception of holistic forms may reduce the visibility of constituent parts. In
      the present experiment, we examined change detection and change identification
      accuracy with Kanizsa rectangle patterns that were arranged to either form a
      Gestalt whole or not. Results from an experiment with 62 participants support
      this trade-off in processing holistic forms. Holistic processing improved the
      detection of change but obstructed its identification. Results are discussed in
      terms of both their theoretical significance and their application in areas
      ranging from baggage screening and the detection of changes in radiological
      images to the systems that are used to generate composite images of perpetrators
      on the basis of eyewitness reports. 

PMID- 24664882
TI  - The nature of altered vision near the hands: evidence for the magnocellular
      enhancement account from object correspondence through occlusion.
AB  - A growing body of evidence indicates that the perception of visual stimuli is
      altered when they occur near the observer's hands, relative to other locations in
      space (see Brockmole, Davoli, Abrams, & Witt, 2013, for a review). Several
      accounts have been offered to explain the pattern of performance across different
      tasks. These have typically focused on attentional explanations (attentional
      prioritization and detailed attentional evaluation of stimuli in near-hand
      space), but more recently, it has been suggested that near-hand space enjoys
      enhanced magnocellular (M) input. Here we differentiate between the attentional
      and M-cell accounts, via a task that probes the roles of position consistency and
      color consistency in determining dynamic object correspondence through occlusion.
      We found that placing the hands near the visual display made observers use only
      position consistency, and not color, in determining object correspondence through
      occlusion, which is consistent with the fact that M cells are relatively
      insensitive to color. In contrast, placing observers' hands far from the stimuli
      allowed both color and position contribute. This provides evidence in favor of
      the M-cell enhancement account of altered vision near the hands. 

PMID- 24664883
TI  - Synovial sarcoma relapses in children and adolescents: prognostic factors,
      treatment, and outcome.
AB  - INTRODUCTION: Twenty-five to 32% of patients with synovial sarcoma (SS) relapse
      after appropriate treatment, and experience a poor outcome. Patients who can be
      salvaged by second-line therapy need to be more clearly identified. PATIENTS AND
      METHODS: Data of patients treated in SFCE (Societe Francaise des Cancers de
      l'Enfant) centers with an initial diagnosis of localized SS before the age of 18
      years and treated from 1/1988 to 12/2008, and who experienced at least one
      relapse, were retrieved. After descriptive analysis, statistical analysis was
      performed to determine prognostic factors. RESULTS: Thirty-seven patients were
      identified. First relapse occurred after a median interval of 24 months and was
      localized in 73.0% of cases and metastatic in 24.3% of cases. Treatment of
      relapse consisted of new surgery in 75.7% of cases, second-line chemotherapy in
      73.0% of cases and radiotherapy in 48.6% of cases. Response rate to ifosfamide
      based regimens was 36.4%. Overall, 70.3% patients achieved a second complete
      remission. Median 5-year-event-free survival was 32.8% and 5-year overall
      survival was 42.1%. Factors significantly correlated with better survival were
      primary tumor involving the limbs, age less than 12 years at diagnosis, absence
      of chemotherapy or radiotherapy as initial treatment and local relapse.
      CONCLUSION: Despite its poor overall outcome, relapse of synovial sarcoma
      sometimes remains curable. Aggressive surgery, when possible, in combination with
      chemotherapy and radiotherapy is the recommended treatment. Ifosfamide-based
      regimens may remain effective in patients with relapsed SS. However, alternative
      therapies should be proposed in patients with poor prognostic factors.

PMID- 24664884
TI  - Polycaprolactone-thiophene-conjugated carbon nanotube meshes as scaffolds for
      cardiac progenitor cells.
AB  - The myocardium is unable to regenerate itself after infarct, resulting in
      scarring and thinning of the heart wall. Our objective was to develop a patch to
      buttress and bypass the scarred area, while allowing regeneration by incorporated
      cardiac stem/progenitor cells (CPCs). Polycaprolactone (PCL) was fabricated as
      both sheets by solvent casting, and fibrous meshes by electrospinning, as
      potential patches, to determine the role of topology in proliferation and
      phenotypic changes to the CPCs. Thiophene-conjugated carbon nanotubes (T-CNTs)
      were incorporated to enhance the mechanical strength. We showed that freshly
      isolated CPCs from murine hearts neither attached nor spread on the PCL sheets,
      both with and without T-CNT. As electrospun meshes, however, both PCL and PCL/T
      CNT supported CPC adhesion, proliferation, and differentiation. The incorporation
      of T-CNT into PCL resulted in a significant increase in mechanical strength but
      no morphological changes to the meshes. In turn, proliferation, but not
      differentiation, of CPCs into cardiomyocytes was enhanced in T-CNT containing
      meshes. We have shown that changing the topology of PCL, a known hydrophobic
      material, dramatically altered its properties, in this case, allowing CPCs to
      survive and differentiate. With further development, PCL/T-CNT meshes or similar
      patches may become a viable strategy to aid restoration of the postmyocardial
      infarction myocardium.

PMID- 24664885
TI  - Synthesis and biological activity of quaternary ammonium salt-type agents
      containing cholesterol and terpenes.
AB  - New quaternary ammonium salt-type compounds with lipophilic cholesterol and
      terpene moieties were synthesized. The compounds showed promising antibacterial
      and antimycobacterial activities. Those compounds containing the cholesterol
      moiety showed significant activity against Staphylococcus aureus, Staphylococcus
      epidermidis, and Enterococcus faecium. On the contrary, the antimycobacterial
      activity increased with the presence of the terpene unit in the molecule. 

PMID- 24664886
TI  - Evidence-based practice exposure and physiotherapy students' behaviour during
      clinical placements: a survey.
AB  - BACKGROUND AND PURPOSE: Physiotherapists are expected to practice in an evidence
      based way. Evidence-based practice (EBP) should be an integral part of the
      curriculum to ensure use of the five EBP steps: asking clinical questions,
      searching for and appraising research evidence, integrating the evidence into
      clinical practice and evaluating this process. The aim of this study was to
      compare self-reported EBP behaviour, abilities and barriers during clinical
      placements reported by five cohorts of final year physiotherapy students' with
      different EBP exposure across the 3-year bachelor programme. METHODS: A cross
      sectional study was conducted among five cohorts (2006-2010) with third year
      physiotherapy students at a University College in Norway. In total, 246 students
      were eligible for this study. To collect data, we used a questionnaire with 42
      items related to EBP behaviour, ability and barriers. Associations were
      investigated using the Spearman's rho (r). RESULTS: In total, 180 out of 246
      third year physiotherapy students, who had recently completed a clinical
      placement, filled out the questionnaire (73 %). The association between the level
      of EBP exposure and students' self-reported EBP behaviour, abilities and barriers
      was low for most items in the questionnaire. Statistically significant
      correlations were found for eight items, related to information need, question
      formulation, use of checklists, searching and perceived ability to search for and
      critically appraise research evidence. The strongest correlation was found
      between the level of EBP exposure and ability to critically appraise research
      evidence (r = 0.41, p < 0.001). CONCLUSIONS: An association between the level of
      EBP exposure and physiotherapy students' EBP behaviour was found for elements
      such as asking and searching, ability to search for and critically appraise
      research evidence, and experience of critical appraisal as a barrier. Further
      research need to explore strategies for EBP exposure throughout the curriculum,
      regarding content, timing, amount and type of training.

PMID- 24664887
TI  - PTX3 stimulates osteoclastogenesis by increasing osteoblast RANKL production.
AB  - Pentraxin-3 (PTX3), also known as tumor necrosis factor-stimulated gene 14 (TSG
      14), is produced by immune and vascular cells in response to pro-inflammatory
      signals and is therefore a multipotent inflammatory mediator. The present study
      showed that during human osteoblast (OB) differentiation, precursor OBs (pOBs),
      but not mature OB, highly expressed PTX3. TNFalpha treatment elevated the PTX3
      expression of pOBs. When mice were injected with lipopolysaccharide, which
      induces an inflammatory osteolytic condition characterized by trabecular bone
      destruction and high osteoclastogenesis, their bone marrow cells expressed
      elevated levels of PTX3 protein. Exogenous PTX3 did not directly affect
      osteoclast (OC) or OB differentiation. However, when pOBs and precursor OCs were
      co-cultured, exogenous PTX3 significantly increased the number of tartrate
      resistant acid phosphatase-positive multinucleated cells (i.e., OC cells) by
      increasing the pOB mRNA expression and protein secretion of RANK ligand (RANKL).
      This was accompanied with increased Runt-related transcription factor 2 (Runx2)
      expression in the pOBs. Knock-down of endogenous PTX3 with small-interfering RNA
      did not change the osteogenic potential of pOBs but suppressed their production
      of RANKL and reduced osteoclastogenesis. Finally, TNFalpha treatment of the co
      culture elevated PTX3 expression by the pOBs and increased OC formation. This
      effect was suppressed by PTX3 knock-down by decreasing RANKL expression. Thus,
      the PTX3-driven increase in the osteoclastogenic potential of pOBs appears to be
      mediated by the effect of PTX3 on pOB RANKL production. These findings suggest
      that PTX3 is an inflammatory mediator that contributes to the deteriorating
      osteolytic condition of inflamed bone. J. Cell. Physiol. 229: 1744-1752, 2014.
      (c) 2014 Wiley Periodicals, Inc. 

PMID- 24664888
TI  - Increased open-circuit voltage of organic solar cells by reduced donor-acceptor
      interface area.

PMID- 24664890
TI  - Single crystals popping under UV light: a photosalient effect triggered by a
      [2+2] cycloaddition reaction.
AB  - The extremely rare examples of dynamic single crystals where excitation by light
      or heat induces macroscopic motility present not only a visually appealing
      demonstration of the utility of molecular materials for conversion of energy to
      work, but they also provide a unique opportunity to explore the mechanistic link
      between collective molecular processes and their consequences at a macroscopic
      level. Here, we report the first example of a photosalient effect (photoinduced
      leaping) observed with crystals of three coordination complexes which is induced
      by a [2+2] photocycloaddition reaction. Unlike a plethora of other dimerization
      reactions, when exposed to even weak UV light, single crystals of these materials
      burst violently, whereby they are propelled to travel several millimeters. The
      results point to a multistep mechanism where the strain energy that has been
      accumulated during the dimerization triggers a rapid structure transformation
      which ultimately results in crystal disintegration. 

PMID- 24664891
TI  - Living with the physical and mental consequences of an ostomy: a study among 1-10
      year rectal cancer survivors from the population-based PROFILES registry.
AB  - BACKGROUND: This study examined the physical and mental consequences of an ostomy
      among 1-10-year rectal cancer survivors. METHODS: Patients with rectal cancer
      diagnosed from 2000 to 2009, as registered in the population-based Eindhoven
      Cancer Registry, received a questionnaire on quality of life (QOL; EORTC QLQ
      C30), disease-specific health status (EORTC QLQ-CR38), depression and anxiety
      (HADS), illness perceptions (Brief Illness Perception Questionnaire), and health
      care utilization; 76% (n = 1019) responded. RESULTS: A total of 408 (43%) rectal
      cancer survivors had an ostomy at survey and they reported a statistically
      significant and clinically relevant lower physical, role, and social functioning,
      and global health status/QOL but fewer problems with constipation and diarrhea
      compared with those without an ostomy. Also, they had a significantly worse body
      image, more male sexual problems, and fewer gastrointestinal problems although
      these differences were not clinically relevant. No differences regarding the
      prevalence of symptoms of anxiety and depression were found. Survivors with an
      ostomy believed that their illness have significantly more serious consequences,
      will last longer (clinically relevant), and were more concerned about their
      illness compared with those without an ostomy. Survivors with an ostomy visited
      their medical specialist, but not their general practitioner, significantly more
      often. Also, they more often received additional support after cancer treatment.
      CONCLUSIONS: Rectal cancer survivors with an ostomy have a lower QOL, worse
      illness perceptions, and a higher health care consumption compared with those
      without an ostomy 1-10 years after diagnosis.

PMID- 24664892
TI  - The E180splice mutation in the GHR gene causing Laron syndrome: witness of a
      Sephardic Jewish exodus from the Iberian Peninsula to the New World?
AB  - Laron syndrome (LS) is a genetic disorder caused by mutations in the growth
      hormone receptor (GHR) gene. The most frequent GHR mutation is E180splice
      (rs121909360), which was initially found in an inbred population of Spanish
      descent in Ecuador and subsequently in Israel, Brazil, Chile, and the United
      States. The aim of the present study is to determine if the E180splice mutation
      arose from a common origin. We studied 22 patients with LS from Ecuador, Israel
      (of Moroccan origin), Brazil, Chile, and the United States (of Mexican origin)
      who were homozygous for the E180splice mutation and compared them to control
      individuals for markers surrounding the GHR, intragenic polymorphisms, and Y
      chromosome STR. An identical haplotype was found in all but one of the subjects
      carrying the E180splice mutation: D5S665: 150/150; D5S2082: 192/192; D5S2087:
      246/246; rs6179 G/G; and rs6180 C/C. One patient differed from the others only at
      D5S2082 (168/192). This haplotype is rare (~1%) in control individuals and
      confirmed that the E180splice-associated haplotype was not derived from
      independent origins but represented recombination from a common ancestor. The
      analysis of paternal lineage markers showed that 50% belong to haplogroup R1b
      (found in Portugal and Spain) and 40% to haplogroups J and E (typical in the
      Middle East and in Eastern European Jews). The germline E180Splice mutation
      appears to have originated from a single common ancestor. The presence of Y
      chromosome markers associated with Sephardic populations in persons harboring the
      E180splice mutation provides genetic evidence in support of the historical
      tracking of the exodus of this specific population.

PMID- 24664894
TI  - Running world cross-country championships: a unique model for pacing.
AB  - The aim of this study was to describe the pacing distribution during 6 editions
      of the world cross-country championships. METHODS: Data from the 768 male runners
      participating from 2007 to 2013 were considered for this study. Blocks of 10
      participants according to final position (eg, 1st to 10th, 11 to 20th, etc) were
      considered. RESULTS: Taking data from all editions together, the effect of years
      was found to be significant (F(5,266) = 3078.69, P < .001, omega2 = 0.31), as
      well as the effect of blocks of runners by final position (F(4,266) = 957.62, P <
      .001, omega2 = 0.08). A significant general decrease in speed by lap was also
      found (F(5,1330) = 2344.02, P < .001, omega2 = 0.29). Post hoc analyses were
      conducted for every edition where several pacing patterns were found. All
      correlations between the lap times and the total time were significant. However,
      each lap might show different predicting capacity over the individual outcome.
      DISCUSSION: Top athletes seem to display different strategies, which allow them
      to sustain an optimal speed and/or kick as needed during the critical moments and
      succeed. After the first group (block) of runners, subsequent blocks always
      displayed a positive pacing pattern (fast to slow speed). Consequently, a much
      more stable pacing pattern should be considered to maximize final position.
      CONCLUSIONS: Top-10 finishers in the world cross-country championships tend to
      display a more even pace than the rest of the finishers, whose general behavior
      shows a positive (fast-to-slow) pattern.

PMID- 24664893
TI  - Relationship between strength, pain, and different measures of functional ability
      in patients with end-stage hip osteoarthritis.
AB  - OBJECTIVE: Performance tests and self-reported questionnaires capture different
      domains of function in patients with lower extremity osteoarthritis, but the
      impairments related to each of these domains have not been elucidated. The
      purpose of this study was to determine how strength and joint pain influence
      performance-based tests and self-reported questionnaires of functional ability of
      individuals with end-stage hip osteoarthritis. METHODS: Fifty-six patients
      scheduled to undergo unilateral total hip arthroplasty were included in this
      cross-sectional analysis. Subjects completed the Hip Outcome Survey (HOS) and
      pain in the affected hip was quantified on a scale from 0-10. Performance-based
      tests included the Six-Minute Walk Test (6MWT), the Timed Up & Go (TUG), and the
      Stair Climbing Test (SCT). Isometric strength of the hip abductors and knee
      extensors was tested and recorded. Hierarchical linear regressions were created
      to determine the contributions of pain, knee extensor strength, and hip strength
      for each outcome measure (TUG, 6MWT, SCT, and HOS). Height and body mass index
      were entered first, followed by pain, then knee extensor strength, and then hip
      abduction strength. RESULTS: Greater pain significantly predicted lower HOS
      scores, but hip strength did not significantly improve the model. Hip pain was
      also significantly related to TUG, SCT, and 6MWT values, but hip and knee
      strength explained additional variance for these performance-based measures.
      CONCLUSION: Self-report and performance-based measures capture different aspects
      of disability and are influenced by different underlying impairments. Both types
      of outcome measures should be used in studies that evaluate functional changes in
      patients with hip osteoarthritis.

PMID- 24664895
TI  - Effect of a Punica granatum enriched diet on immunocompetence in Rhinella marina.
AB  - Direct ingestion of plant materials has been shown to have immunomodulatory
      effects on a variety of herbivores. Studies have also shown that compounds
      ingested indirectly by predators through prey items can affect the general
      physiology of the ingesting organism. Relatively little data exists, however,
      concerning the modulation of a predator's immune system via compounds obtained
      indirectly through prey. In this study, we sought to determine if the immune
      stimulating properties of Punica granatum (pomegranate) could be conveyed from a
      prey organism, Acheta domestica, to a predator, Rhinella marina, through diet
      specialization. Experimental crickets were fed a diet of agar supplemented with
      10 mg/mL of lyophilized, powdered, whole pomegranate while control crickets were
      fed unadulterated agar. Experimental toads consumed a diet consisting of crickets
      fed the pomegranate-enriched diet, while control toads consumed a diet consisting
      of crickets fed the standard agar diet. Blood samples were taken weekly and
      leukocyte profiles and neutrophil phagocytic activity were determined for all
      toads over an 8-week period. Complement activity was measured at 6 weeks. Toads
      fed the pomegranate-enriched diet showed altered leukocyte profiles as evidenced
      by an increase in circulating eosinophil number and a decrease in the number of
      circulating lymphocytes, monocytes, and basophils as compared to controls,
      indicating an immunomodulatory effect of the pomegranate-enhanced diet. These
      results suggest that pomegranate-derived immunomodulatory compounds can be
      transferred from prey to predator, and suggests that the flora in the environment
      where insectivores forage could have a significant effect on the physiology of
      the animal.

PMID- 24664903
TI  - Fertility decline, girls' well-being, and gender gaps in children's well-being in
      poor countries.
AB  - The influences of recent dramatic declines in fertility on girls' and boys' well
      being in poorer countries are understudied. In panels of 67-75 poorer countries,
      using 152-185 Demographic and Health Surveys spanning 1985-2008, we examined how
      declining total fertility and women's increasing median age at first birth were
      associated with changes in girls' well-being and gender gaps in children's well
      being, as reflected in their survival, nutrition, and access to preventive
      healthcare. In adjusted random-effects models, these changes in fertility were
      associated with gains in girls' survival at ages 1-4 years, vaccination coverage
      at ages 12-23 months, and nutrition at 0-36 months (for women's later first
      childbearing). Declining total fertility was associated with similar gains for
      boys and girls with respect to vaccination coverage but intensified gender gaps
      in mortality at ages 1-4 years and malnutrition at ages 0-36 months, especially
      in higher-son-preference populations. Later increases in women's median age at
      first birth-reflecting more equitable gender norms-were associated with declines
      in these gaps. Promoting equitable investments in children through family
      planning programs in higher-fertility societies is warranted. 

PMID- 24664906
TI  - Parental and physician attitudes toward medulloblastoma treatment.

PMID- 24664904
TI  - Evidence for an interaction between exercise and nutrition for improving bone and
      muscle health.
AB  - Regular exercise and adequate nutrition, particularly dietary calcium, vitamin D,
      and protein, are prescribed as strategies to optimize peak bone mass and maintain
      bone and muscle health throughout life. Although the mechanism of action of
      exercise and nutrition on bone and muscle health are different-exercise has a
      site-specific modifying effect, whereas nutrition has a permissive generalized
      effect-there is evidence that combining calcium (or calcium rich dairy foods) or
      dietary protein with exercise can have a synergetic effect on bone mass and
      muscle health, respectively. However, many questions still remain as to whether
      there is a threshold level for these nutrients to optimize the exercise-induced
      gains. Further studies are also needed to investigate whether other dietary
      factors, such as vitamin D, soy isoflavones or omega-3 fatty acids, or a
      multinutrient supplement, can enhance the effects of exercise on bone and muscle
      health.

PMID- 24664907
TI  - The application of a thermoresponsive chitosan/beta-GP gel to enhance cell
      repopulation of decellularized vascular scaffolds.
AB  - Decellularized arterial scaffolds have achieved success in advancing towards
      clinical use for small diameter vascular graft applications. Issues remain with
      effectively cell seeding these scaffolds, which may result in slow remodeling in
      vivo and reduced patency rates. This study aims to efficiently bulk load
      decellularized arterial scaffolds with cells and/or growth factors to promote
      cell migration within the scaffold. A chitosan/beta-glycerophosphate (beta-GP)
      hydrogel was used as a delivery vehicle for scaffold repopulation with rat
      mesenchymal stem cells (rMSCs) and/or murine hepatocyte growth factor (HGF). The
      thermoresponsivity of the chitosan/beta-GP HGF gel was determined by rheological
      analysis and the release of HGF by ELISA. The chitosan/beta-GP gel was fully
      injectable with gelation at 30 degrees C in ~30 min and demonstrated sustained
      controlled HGF release up to 28 days. Encapsulation of rMSCs allowed for
      consistent efficient cell delivery within the scaffold. Directional migration
      toward the released HGF was demonstrated within the medial layer of the scaffold
      up to a distance of 3 mm. The gel/cell/growth factor combination demonstrates a
      means of accelerating scaffold repopulation, without costly excessive in vitro
      maturation times.

PMID- 24664908
TI  - p16INK4a, NAD(+) , and sestrins: new targets for combating aging-related chronic
      illness?
AB  - Aging-related chronic illness is a price we have to pay to live longer. Prevalent
      among the oldest old, the condition limits their functional independence and also
      aggravates the course of several age-related chronic diseases. Thus, the search
      is on for efficient therapies that will mitigate age-related pathologies. In this
      article, we point out the potential clinical implications of recent provocative
      basic research in the field. New possible targets have been recently discovered,
      are clearly involved in age-related pathologies and might benefit the treatment
      of other age-related conditions, particularly metabolic diseases.

PMID- 24664896
TI  - The multifaceted roles of RNA binding in APOBEC cytidine deaminase functions.
AB  - Cytidine deaminases have important roles in the regulation of
      nucleoside/deoxynucleoside pools for DNA and RNA synthesis. The APOBEC family of
      cytidine deaminases (named after the first member of the family that was
      described, Apolipoprotein B mRNA Editing Catalytic Subunit 1, also known as
      APOBEC1 or A1) is a fascinating group of mutagenic proteins that use RNA and
      single-stranded DNA (ssDNA) as substrates for their cytidine or deoxycytidine
      deaminase activities. APOBEC proteins and base-modification nucleic acid editing
      have been the subject of numerous publications, reviews, and speculation. These
      proteins play diverse roles in host cell defense, protecting cells from invading
      genetic material, enabling the acquired immune response to antigens and changing
      protein expression at the level of the genetic code in mRNA or DNA. The amazing
      power these proteins have for interphase cell functions relies on structural and
      biochemical properties that are beginning to be understood. At the same time, the
      substrate selectivity of each member in the family and their regulation remains
      to be elucidated. This review of the APOBEC family will focus on an open question
      in regulation, namely what role the interactions of these proteins with RNA have
      in editing substrate recognition or allosteric regulation of DNA mutagenic and
      host-defense activities.

PMID- 24664909
TI  - Barriers to recruitment in psycho-oncology: unique challenges in conducting
      research focusing on sexual health in female survivorship.

PMID- 24664910
TI  - Exploring the diversity of Jupiter-class planets.
AB  - Of the 900+ confirmed exoplanets discovered since 1995 for which we have
      constraints on their mass (i.e. not including Kepler candidates), 75% have masses
      larger than Saturn (0.3 MJ), 53% are more massive than Jupiter and 67% are within
      1 AU of their host stars. When Kepler candidates are included, Neptune-sized
      giant planets could form the majority of the planetary population. And yet the
      term 'hot Jupiter' fails to account for the incredible diversity of this class of
      astrophysical object, which exists on a continuum of giant planets from the cool
      jovians of our own Solar System to the highly irradiated, tidally locked hot
      roasters. We review theoretical expectations for the temperatures, molecular
      composition and cloud properties of hydrogen-dominated Jupiter-class objects
      under a variety of different conditions. We discuss the classification schemes
      for these Jupiter-class planets proposed to date, including the implications for
      our own Solar System giant planets and the pitfalls associated with compositional
      classification at this early stage of exoplanetary spectroscopy. We discuss the
      range of planetary types described by previous authors, accounting for (i)
      thermochemical equilibrium expectations for cloud condensation and favoured
      chemical stability fields; (ii) the metallicity and formation mechanism for these
      giant planets; (iii) the importance of optical absorbers for energy partitioning
      and the generation of a temperature inversion; (iv) the favoured photochemical
      pathways and expectations for minor species (e.g. saturated hydrocarbons and
      nitriles); (v) the unexpected presence of molecules owing to vertical mixing of
      species above their quench levels; and (vi) methods for energy and material
      redistribution throughout the atmosphere (e.g. away from the highly irradiated
      daysides of close-in giants). Finally, we discuss the benefits and potential
      flaws of retrieval techniques for establishing a family of atmospheric solutions
      that reproduce the available data, and the requirements for future spectroscopic
      characterization of a set of Jupiter-class objects to test our physical and
      chemical understanding of these planets. 

PMID- 24664911
TI  - Scenarios of giant planet formation and evolution and their impact on the
      formation of habitable terrestrial planets.
AB  - In our Solar System, there is a clear divide between the terrestrial and giant
      planets. These two categories of planets formed and evolved separately, almost in
      isolation from each other. This was possible because Jupiter avoided migrating
      into the inner Solar System, most probably due to the presence of Saturn, and
      never acquired a large-eccentricity orbit, even during the phase of orbital
      instability that the giant planets most likely experienced. Thus, the Earth
      formed on a time scale of several tens of millions of years, by collision of Moon
      to Mars-mass planetary embryos, in a gas-free and volatile-depleted environment.
      We do not expect, however, that this clear cleavage between the giant and
      terrestrial planets is generic. In many extrasolar planetary systems discovered
      to date, the giant planets migrated into the vicinity of the parent star and/or
      acquired eccentric orbits. In this way, the evolution and destiny of the giant
      and terrestrial planets become intimately linked. This paper discusses several
      evolutionary patterns for the giant planets, with an emphasis on the consequences
      for the formation and survival of habitable terrestrial planets. The conclusion
      is that we should not expect Earth-like planets to be typical in terms of
      physical and orbital properties and accretion history. Most habitable worlds are
      probably different, exotic worlds. 

PMID- 24664912
TI  - Chemical kinetics on extrasolar planets.
AB  - Chemical kinetics plays an important role in controlling the atmospheric
      composition of all planetary atmospheres, including those of extrasolar planets.
      For the hottest exoplanets, the composition can closely follow thermochemical
      equilibrium predictions, at least in the visible and infrared photosphere at
      dayside (eclipse) conditions. However, for atmospheric temperatures approximately
      <2000K, and in the uppermost atmosphere at any temperature, chemical kinetics
      matters. The two key mechanisms by which kinetic processes drive an exoplanet
      atmosphere out of equilibrium are photochemistry and transport-induced quenching.
      I review these disequilibrium processes in detail, discuss observational
      consequences and examine some of the current evidence for kinetic processes on
      extrasolar planets.

PMID- 24664913
TI  - Planetary system formation in thermally evolving viscous protoplanetary discs.
AB  - Observations of extrasolar planets are providing new opportunities for furthering
      our understanding of planetary formation processes. In this paper, we review
      planet formation and migration scenarios and describe some recent simulations
      that combine planetary accretion and gas-disc-driven migration. While the
      simulations are successful at forming populations of low- and intermediate-mass
      planets with short orbital periods, similar to those that are being observed by
      ground- and space-based surveys, our models fail to form any gas giant planets
      that survive migration into the central star. The simulation results are
      contrasted with observations, and areas of future model development are
      discussed. 

PMID- 24664914
TI  - High-dispersion spectroscopy of extrasolar planets: from CO in hot Jupiters to O2
      in exo-Earths.
AB  - Ground-based high-dispersion spectroscopy could reveal molecular oxygen as a
      biomarker gas in the atmospheres of twin-Earths transiting red dwarf stars within
      the next 25 years. The required contrasts are only a factor of 3 lower than that
      already achieved for carbon monoxide in hot Jupiter atmospheres today but will
      need much larger telescopes because the target stars will be orders of magnitude
      fainter. If extraterrestrial life is very common and can therefore be found on
      planets around the most nearby red dwarf stars, it may be detectable via
      transmission spectroscopy with the next-generation extremely large telescopes.
      However, it is likely that significantly more collecting area is required for
      this. This can be achieved through the development of low-cost flux collector
      technology, which combines a large collecting area with a low but sufficient
      image quality for high-dispersion spectroscopy of bright stars. 

PMID- 24664915
TI  - Melting in super-earths.
AB  - We examine the possible extent of melting in rock-iron super-earths, focusing on
      those in the habitable zone. We consider the energetics of accretion and core
      formation, the timescale of cooling and its dependence on viscosity and partial
      melting, thermal regulation via the temperature dependence of viscosity, and the
      melting curves of rock and iron components at the ultra-high pressures
      characteristic of super-earths. We find that the efficiency of kinetic energy
      deposition during accretion increases with planetary mass; considering the likely
      role of giant impacts and core formation, we find that super-earths probably
      complete their accretionary phase in an entirely molten state. Considerations of
      thermal regulation lead us to propose model temperature profiles of super-earths
      that are controlled by silicate melting. We estimate melting curves of iron and
      rock components up to the extreme pressures characteristic of super-earth
      interiors based on existing experimental and ab initio results and scaling laws.
      We construct super-earth thermal models by solving the equations of mass
      conservation and hydrostatic equilibrium, together with equations of state of
      rock and iron components. We set the potential temperature at the core-mantle
      boundary and at the surface to the local silicate melting temperature. We find
      that ancient (~4 Gyr) super-earths may be partially molten at the top and bottom
      of their mantles, and that mantle convection is sufficiently vigorous to sustain
      dynamo action over the whole range of super-earth masses. 

PMID- 24664916
TI  - Galactic planetary science.
AB  - Planetary science beyond the boundaries of our Solar System is today in its
      infancy. Until a couple of decades ago, the detailed investigation of the
      planetary properties was restricted to objects orbiting inside the Kuiper Belt.
      Today, we cannot ignore that the number of known planets has increased by two
      orders of magnitude nor that these planets resemble anything but the objects
      present in our own Solar System. Whether this fact is the result of a selection
      bias induced by the kind of techniques used to discover new planets--mainly
      radial velocity and transit--or simply the proof that the Solar System is a
      rarity in the Milky Way, we do not know yet. What is clear, though, is that the
      Solar System has failed to be the paradigm not only in our Galaxy but even 'just'
      in the solar neighbourhood. This finding, although unsettling, forces us to
      reconsider our knowledge of planets under a different light and perhaps question
      a few of the theoretical pillars on which we base our current 'understanding'.
      The next decade will be critical to advance in what we should perhaps call
      Galactic planetary science. In this paper, I review highlights and pitfalls of
      our current knowledge of this topic and elaborate on how this knowledge might
      arguably evolve in the next decade. More critically, I identify what should be
      the mandatory scientific and technical steps to be taken in this fascinating
      journey of remote exploration of planets in our Galaxy.

PMID- 24664917
TI  - Habitable worlds with no signs of life.
AB  - 'Most habitable worlds in the cosmos will have no remotely detectable signs of
      life' is proposed as a biological hypothesis to be tested in the study of
      exoplanets. Habitable planets could be discovered elsewhere in the Universe, yet
      there are many hypothetical scenarios whereby the search for life on them could
      yield negative results. Scenarios for habitable worlds with no remotely
      detectable signatures of life include: planets that are habitable, but have no
      biosphere (Uninhabited Habitable Worlds); planets with life, but lacking any
      detectable surface signatures of that life (laboratory examples are provided);
      and planets with life, where the concentrations of atmospheric gases produced or
      removed by biota are impossible to disentangle from abiotic processes because of
      the lack of detailed knowledge of planetary conditions (the 'problem of exoplanet
      thermodynamic uncertainty'). A rejection of the hypothesis would require that the
      origin of life usually occurs on habitable planets, that spectrally detectable
      pigments and/or metabolisms that produce unequivocal biosignature gases (e.g.
      oxygenic photosynthesis) usually evolve and that the organisms that harbour them
      usually achieve a sufficient biomass to produce biosignatures detectable to alien
      astronomers. 

PMID- 24664918
TI  - Infrared spectroscopy of exoplanets: observational constraints.
AB  - The exploration of transiting extrasolar planets is an exploding research area in
      astronomy. With more than 400 transiting exoplanets identified so far, these
      discoveries have made possible the development of a new research field, the
      spectroscopic characterization of exoplanets' atmospheres, using both primary and
      secondary transits. However, these observations have been so far limited to a
      small number of targets. In this paper, we first review the advantages and
      limitations of both primary and secondary transit methods. Then, we analyse what
      kind of infrared spectra can be expected for different types of planets and
      discuss how to optimize the spectral range and the resolving power of the
      observations. Finally, we propose a list of favourable targets for present and
      future ground-based observations. 

PMID- 24664919
TI  - Possible climates on terrestrial exoplanets.
AB  - What kind of environment may exist on terrestrial planets around other stars? In
      spite of the lack of direct observations, it may not be premature to speculate on
      exoplanetary climates, for instance, to optimize future telescopic observations
      or to assess the probability of habitable worlds. To begin with, climate
      primarily depends on (i) the atmospheric composition and the volatile inventory;
      (ii) the incident stellar flux; and (iii) the tidal evolution of the planetary
      spin, which can notably lock a planet with a permanent night side. The
      atmospheric composition and mass depends on complex processes, which are
      difficult to model: origins of volatiles, atmospheric escape, geochemistry,
      photochemistry, etc. We discuss physical constraints, which can help us to
      speculate on the possible type of atmosphere, depending on the planet size, its
      final distance for its star and the star type. Assuming that the atmosphere is
      known, the possible climates can be explored using global climate models
      analogous to the ones developed to simulate the Earth as well as the other
      telluric atmospheres in the solar system. Our experience with Mars, Titan and
      Venus suggests that realistic climate simulators can be developed by combining
      components, such as a 'dynamical core', a radiative transfer solver, a
      parametrization of subgrid-scale turbulence and convection, a thermal ground
      model and a volatile phase change code. On this basis, we can aspire to build
      reliable climate predictors for exoplanets. However, whatever the accuracy of the
      models, predicting the actual climate regime on a specific planet will remain
      challenging because climate systems are affected by strong positive feedbacks.
      They can drive planets with very similar forcing and volatile inventory to
      completely different states. For instance, the coupling among temperature,
      volatile phase changes and radiative properties results in instabilities, such as
      runaway glaciations and runaway greenhouse effect. 

PMID- 24664920
TI  - Disentangling degenerate solutions from primary transit and secondary eclipse
      spectroscopy of exoplanets.
AB  - Infrared transmission and emission spectroscopy of exoplanets, recorded from
      primary transit and secondary eclipse measurements, indicate the presence of the
      most abundant carbon and oxygen molecular species (H2O, CH4, CO and CO2) in a few
      exoplanets. However, efforts to constrain the molecular abundances to within
      several orders of magnitude are thwarted by the broad range of degenerate
      solutions that fit the data. Here, we explore, with radiative transfer models and
      analytical approximations, the nature of the degenerate solution sets resulting
      from the sparse measurements of 'hot Jupiter' exoplanets. As demonstrated with
      simple analytical expressions, primary transit measurements probe roughly four
      atmospheric scale heights at each wavelength band. Derived mixing ratios from
      these data are highly sensitive to errors in the radius of the planet at a
      reference pressure. For example, an uncertainty of 1% in the radius of a 1000 K
      and H2-based exoplanet with Jupiter's radius and mass causes an uncertainty of a
      factor of approximately 100-10,000 in the derived gas mixing ratios. The degree
      of sensitivity depends on how the line strength increases with the optical depth
      (i.e. the curve of growth) and the atmospheric scale height. Temperature
      degeneracies in the solutions of the primary transit data, which manifest their
      effects through the scale height and absorption coefficients, are smaller. We
      argue that these challenges can be partially surmounted by a combination of
      selected wavelength sampling of optical and infrared measurements and, when
      possible, the joint analysis of transit and secondary eclipse data of exoplanets.
      However, additional work is needed to constrain other effects, such as those
      owing to planetary clouds and star spots. Given the current range of open
      questions in the field, both observations and theory, there is a need for
      detailed measurements with space-based large mirror platforms (e.g. James web
      space telescope) and smaller broad survey telescopes as well as ground-based
      efforts.

PMID- 24664921
TI  - Molecular opacities for exoplanets.
AB  - Spectroscopic observations of exoplanets are now possible by transit methods and
      direct emission. Spectroscopic requirements for exoplanets are reviewed based on
      existing measurements and model predictions for hot Jupiters and super-Earths.
      Molecular opacities needed to simulate astronomical observations can be obtained
      from laboratory measurements, ab initio calculations or a combination of the two
      approaches. This discussion article focuses mainly on laboratory measurements of
      hot molecules as needed for exoplanet spectroscopy. 

PMID- 24664922
TI  - Radial velocity studies of cool stars.
AB  - Our current view of exoplanets is one derived primarily from solar-like stars
      with a strong focus on understanding our Solar System. Our knowledge about the
      properties of exoplanets around the dominant stellar population by number, the so
      called low-mass stars or M dwarfs, is much more cursory. Based on radial velocity
      discoveries, we find that the semi-major axis distribution of M dwarf planets
      appears to be broadly similar to those around more massive stars and thus
      formation and migration processes might be similar to heavier stars. However, we
      find that the mass of M dwarf planets is relatively much lower than the expected
      mass dependency based on stellar mass and thus infer that planet formation
      efficiency around low-mass stars is relatively impaired. We consider techniques
      to overcome the practical issue of obtaining good quality radial velocity data
      for M dwarfs despite their faintness and sustained activity and emphasize (i) the
      wavelength sensitivity of radial velocity signals, (ii) the combination of radial
      velocity data from different experiments for robust detection of small amplitude
      signals, and (iii) the selection of targets and radial velocity interpretation of
      late-type M dwarfs should consider Halpha behaviour. 

PMID- 24664923
TI  - Thermal escape from extrasolar giant planets.
AB  - The detection of hot atomic hydrogen and heavy atoms and ions at high altitudes
      around close-in extrasolar giant planets (EGPs) such as HD209458b implies that
      these planets have hot and rapidly escaping atmospheres that extend to several
      planetary radii. These characteristics, however, cannot be generalized to all
      close-in EGPs. The thermal escape mechanism and mass loss rate from EGPs depend
      on a complex interplay between photochemistry and radiative transfer driven by
      the stellar UV radiation. In this study, we explore how these processes change
      under different levels of irradiation on giant planets with different
      characteristics. We confirm that there are two distinct regimes of thermal escape
      from EGPs, and that the transition between these regimes is relatively sharp. Our
      results have implications for thermal mass loss rates from different EGPs that we
      discuss in the context of currently known planets and the detectability of their
      upper atmospheres. 

PMID- 24664924
TI  - Direct imaging of exoplanets.
AB  - Most of the exoplanets known today have been discovered by indirect techniques,
      based on the study of the host star radial velocity or photometric temporal
      variations. These detections allowed the study of the planet populations in the
      first 5-8 AU from the central stars and have provided precious information on the
      way planets form and evolve at such separations. Direct imaging on 8-10 m class
      telescopes allows the detection of giant planets at larger separations (currently
      typically more than 5-10 AU) complementing the indirect techniques. So far, only
      a few planets have been imaged around young stars, but each of them provides an
      opportunity for unique dedicated studies of their orbital, physical and
      atmospheric properties and sometimes also on the interaction with the 'second
      generation', debris discs. These few detections already challenge formation
      theories. In this paper, I present the results of direct imaging surveys obtained
      so far, and what they already tell us about giant planet (GP) formation and
      evolution. Individual and emblematic cases are detailed; they illustrate what
      future instruments will routinely deliver for a much larger number of stars. I
      also point out the limitations of this approach, as well as the needs for further
      work in terms of planet formation modelling. I finally present the progress
      expected in direct imaging in the near future, thanks in particular to
      forthcoming planet imagers on 8-10 m class telescopes. 

PMID- 24664925
TI  - Very high-density planets: a possible remnant of gas giants.
AB  - Data extracted from the Extrasolar Planets Encyclopaedia (see
      http://exoplanet.eu) show the existence of planets that are more massive than
      iron cores that would have the same size. After meticulous verification of the
      data, we conclude that the mass of the smallest of these planets is actually not
      known. However, the three largest planets, Kepler-52b, Kepler-52c and Kepler-57b,
      which are between 30 and 100 times the mass of the Earth, have indeed density
      larger than an iron planet of the same size. This observation triggers this study
      that investigates under which conditions these planets could represent the naked
      cores of gas giants that would have lost their atmospheres during their migration
      towards the star. This study shows that for moderate viscosity values (10(25) Pa
      s or lower), large values of escape rate and associated unloading stress rate
      during the atmospheric loss process lead to the explosion of extremely massive
      planets. However, for moderate escape rate, the bulk viscosity and finite-strain
      incompressibility of the cores of giant planets can be large enough to retain a
      very high density during geological time scales. This would make those a new kind
      of planet, which would help in understanding the interior structure of the gas
      giants. However, this new family of exoplanets adds some degeneracy for
      characterizing terrestrial exoplanets.

PMID- 24664926
TI  - Characterizing exoplanets.

PMID- 24664927
TI  - In vivo measurement of apparent diffusion coefficients of hyperpolarized 13C
      labeled metabolites.
AB  - The combination of hyperpolarized MRS with diffusion weighting (dw) allows for
      determination of the apparent diffusion coefficient (ADC), which is indicative of
      the intra- or extracellular localization of the metabolite. Here, a slice
      selective pulsed-gradient spin echo sequence was implemented to acquire a series
      of dw spectra from rat muscle in vivo to determine the ADCs of multiple
      metabolites after a single injection of hyperpolarized [1- 13C]pyruvate. An
      optimal control optimized universal-rotation pulse was used for refocusing to
      minimize signal loss caused by B1 imperfections. Non-dw spectra were acquired
      interleaved with the dw spectra and these were used to correct for signal decay
      during the acquisition as a result of T1 decay, pulse imperfections, flow etc.
      The data showed that the ADC values for [1- 13C]lactate (0.4-0.7 um2 /ms) and [1-
      13C]alanine (0.4-0.9 um2 /ms) were about a factor of two lower than the ADC of [1
      13C]pyruvate (1.1-1.5 um2/ms). This indicates a more restricted diffusion space
      for the former two metabolites consistent with lactate and alanine being
      intracellular. The higher ADC for pyruvate (similar to the proton ADC) reflected
      that the injected substance was not confined inside the muscle cells but also
      present extracellular.

PMID- 24664928
TI  - Construction of chiral bridged tricyclic benzopyrans: enantioselective catalytic
      Diels-Alder reaction and a one-pot reduction/acid-catalyzed stereoselective
      cyclization.
AB  - An asymmetric two-step approach to chiral bridged tricyclic benzopyrans, core
      structures featured in various natural products, is described. In the synthesis,
      an unprecedented enantioselective catalytic decarboxylative Diels-Alder reaction
      is developed using readily available coumarin-3-carboxylic acids and aldehydes as
      reactants under mild reaction conditions. Notably, the decarboxylation-assisted
      release of the catalyst enables the process to proceed efficiently with high
      enantio- and diastereoselectivity. Furthermore, a one-pot procedure for either a
      LiAlH4 - or NaBH4 -mediated reduction with subsequent acid-catalyzed
      intramolecular cyclization of the Diels-Alder adducts was identified for the
      efficient formation of the chiral bridged tricyclic benzopyrans. 

PMID- 24664930
TI  - Effect of maternal anxiety on maternal serum and fetal cord blood cortisol.
AB  - INTRODUCTION: Prenatal exposure to maternal anxiety and inappropriate levels of
      glucocorticoids may influence intrauterine growth and affect later health
      outcomes. We examined the relationship between maternal anxiety, maternal serum,
      and fetal cord blood cortisol. METHODS: Eighty-four pregnant women with
      gestational age above 37 weeks admitted for elective caesarian section were
      studied. The Spielberger State-Trait Anxiety Inventory was used to assess
      maternal anxiety. Maternal blood was sampled immediately before caesarean
      section. Cord blood sample was taken immediately after birth. Multiple regression
      analysis was performed. RESULTS: Maternal trait anxiety score, maternal serum
      cortisol, and neonatal weight were associated with the fetal cord blood cortisol
      (r = 0.21, P = 0.04). Bivariate correlation analysis revealed a positive
      correlation between maternal trait anxiety and fetal cord blood cortisol (r =
      0.21, P = 0.03). CONCLUSIONS: These data suggested that high maternal trait
      anxiety increases fetus cord blood cortisol and may regulate fetal growth.

PMID- 24664931
TI  - An intragenic deletion of the gene MNAT1 in a family with pectus deformities.
AB  - Pectus carinatum and excavatum have multiple genetic associations. We report on a
      novel association of these deformities in a 34-month-old male and his father,
      likely due to a small intragenic deletion of MNAT1 (menage a trois 1 gene). Both
      individuals share a deletion of MNAT1 located at 14q23.1 and an interstitial
      duplication of CHRNA7 located at 15q13.3. Deletion of MNAT1 has been associated
      with connective tissue abnormalities and is likely the etiology of the
      malformations, whereas the duplication of CHNRA7 is unlikely related due to the
      lack of association with any such connective tissue abnormalities.

PMID- 24664932
TI  - Novel acyclic phosphonylated 1,2,3-triazolonucleosides with an acetamidomethyl
      linker: synthesis and biological activity.
AB  - A new series of 4-substituted [(1,2,3-triazol-1-yl)acetamido]methylphosphonates
      as acyclic nucleotide analogs were synthesized from diethyl (2
      chloroacetamido)methylphosphonate via azidation followed by 1,3-dipolar
      cycloaddition with selected alkynes derived from natural nucleobases or their
      mimetics. All compounds were tested for their antiviral activities against DNA
      and RNA viruses as well as for cytostatic activity or cytotoxicity. Among all
      tested compounds, [(1,2,3-triazol-1-yl)acetamido]methylphosphonate 6e substituted
      with the N(3)-Bz-benzuracil moiety showed activity against the vesicular
      stomatitis virus (EC50 = 45 uM) in HeLa cell cultures.

PMID- 24664933
TI  - A universal strategy to prepare functional porous graphene hybrid architectures.

PMID- 24664934
TI  - Responses to exercise in normobaric hypoxia: comparison of elite and recreational
      ski mountaineers.
AB  - PURPOSE: Hypoxia is known to reduce maximal oxygen uptake (VO(2max)) more in
      trained than in untrained subjects in several lowland sports. Ski mountaineering
      is practiced mainly at altitude, so elite ski mountaineers spend significantly
      longer training duration at altitude than their lower-level counterparts. Since
      acclimatization in hypobaric hypoxia is effective, the authors hypothesized that
      elite ski mountaineers would exhibit a VO2max decrement in hypoxia similar to
      that of recreational ski mountaineers. METHODS: Eleven elite (E, Swiss national
      team) and 12 recreational (R) ski mountaineers completed an incremental treadmill
      test to exhaustion in normobaric hypoxia (H, 3000 m, F(1)O(2) 14.6% +/- 0.1%) and
      in normoxia (N, 485 m, F(1)O(2) 20.9% +/- 0.0%). Pulse oxygen saturation in blood
      (SpO(2)), VO(2max), minute ventilation, and heart rate were recorded. RESULTS: At
      rest, hypoxic ventilatory response was higher (P < .05) in E than in R (1.4 +/-
      1.9 vs 0.3 +/- 0.6 L . min-1 . kg-1). At maximal intensity, SpO(2) was
      significantly lower (P < .01) in E than in R, both in N (91.1% +/- 3.3% vs 94.3%
      +/- 2.3%) and in H (76.4% +/- 5.4% vs 82.3% +/- 3.5%). In both groups, SpO(2) was
      lower (P < .01) in H. Between N and H, VO(2max) decreased to a greater extent (P
      < .05) in E than in R (-18% and -12%, P < .01). In E only, the VO(2max) decrement
      was significantly correlated with the SpO(2) decrement (r = .74, P < .01) but
      also with VO(2max) measured in N (r = .64, P < .05). CONCLUSION: Despite a
      probable better acclimatization to altitude, VO(2max) was more reduced in E than
      in R ski mountaineers, confirming previous results observed in lowlander E
      athletes.

PMID- 24664935
TI  - Early tumor necrosis factor alpha antagonist therapy in everyday practice for
      inflammatory back pain suggesting axial spondyloarthritis: results from a
      prospective multicenter french cohort.
AB  - OBJECTIVE: To determine the frequency of and factors associated with early tumor
      necrosis factor alpha (TNFalpha) antagonist therapy in everyday clinical practice
      in patients with suspected axial spondyloarthropathy (SpA). METHODS: We used data
      from the prospective observational study in the French Devenir des
      Spondylarthropathies Indifferenciees Recentes (DESIR; Outcome of Recent
      Undifferentiated Spondylarthropathies) cohort of 708 patients with recent-onset
      (<3 years) inflammatory back pain (IBP) suggesting axial SpA. TNFalpha antagonist
      use was recorded at months 6 and 12 and factors independently associated with
      TNFalpha antagonist therapy were identified by multivariate logistic regression.
      RESULTS: Among the 708 patients (mean age 33.8 years, 46.2% men), 166 (23.4%)
      patients received TNFalpha antagonist therapy by month 12, including 120 (73.6%)
      patients who fulfilled Assessment of SpondyloArthritis international Society
      (ASAS) axial criteria and 157 (94.6%) who fulfilled at least 1 SpA criteria set;
      109 (65.6%) had no sacroiliitis. Factors independently associated with early
      TNFalpha antagonist therapy were high Ankylosing Spondylitis Disease Activity
      Score using the C-reactive protein level (odds ratio [OR]1-point increase 1.60,
      95% confidence interval [95% CI] 1.25-2.03, P < 0.001), high physician's global
      disease activity score (OR 1.37, 95% CI 1.21-1.54, P < 0.001), ASAS nonsteroidal
      antiinflammatory drug score >50 (OR 1.88, 95% CI 1.24-2.87, P = 0.003), current
      or past disease-modifying antirheumatic drug use (OR 2.09, 95% CI 1.22-3.59, P =
      0.008), systemic corticosteroid use (OR 2.48, 95% CI 1.43-4.34, P = 0.002), and
      mild to severe radiographic hip abnormalities (OR 9.43, 95% CI 2.11-42.09, P =
      0.003). After adjustment on these factors, Achilles enthesis hypervascularization
      by power Doppler and number of work days missed were associated with TNFalpha
      antagonist therapy. CONCLUSION: In the DESIR cohort, approximately one-fourth of
      patients with recent IBP suggestive of axial SpA were under anti-TNFalpha therapy
      after 1 year of followup. All factors associated with this early initiation
      reflected higher disease activity, refractoriness, or severity, which suggests
      compliance of French rheumatologists with current treatment guidelines.

PMID- 24664936
TI  - A repeated-measures analysis of the effects of soft tissues on wrist range of
      motion in the extant phylogenetic bracket of dinosaurs: Implications for the
      functional origins of an automatic wrist folding mechanism in Crocodilia.
AB  - A recent study hypothesized that avian-like wrist folding in quadrupedal
      dinosaurs could have aided their distinctive style of locomotion with semi
      pronated and therefore medially facing palms. However, soft tissues that
      automatically guide avian wrist folding rarely fossilize, and automatic wrist
      folding of unknown function in extant crocodilians has not been used to test this
      hypothesis. Therefore, an investigation of the relative contributions of soft
      tissues to wrist range of motion (ROM) in the extant phylogenetic bracket of
      dinosaurs, and the quadrupedal function of crocodilian wrist folding, could
      inform these questions. Here, we repeatedly measured wrist ROM in degrees through
      fully fleshed, skinned, minus muscles/tendons, minus ligaments, and skeletonized
      stages in the American alligator Alligator mississippiensis and the ostrich
      Struthio camelus. The effects of dissection treatment and observer were
      statistically significant for alligator wrist folding and ostrich wrist flexion,
      but not ostrich wrist folding. Final skeletonized wrist folding ROM was higher
      than (ostrich) or equivalent to (alligator) initial fully fleshed ROM, while
      final ROM was lower than initial ROM for ostrich wrist flexion. These findings
      suggest that, unlike the hinge/ball and socket-type elbow and shoulder joints in
      these archosaurs, ROM within gliding/planar diarthrotic joints is more restricted
      to the extent of articular surfaces. The alligator data indicate that the
      crocodilian wrist mechanism functions to automatically lock their semi-pronated
      palms into a rigid column, which supports the hypothesis that this palmar
      orientation necessitated soft tissue stiffening mechanisms in certain dinosaurs,
      although ROM-restricted articulations argue against the presence of an extensive
      automatic mechanism. Anat Rec, 297:1228-1249, 2014. (c) 2014 Wiley Periodicals,
      Inc. 

PMID- 24664937
TI  - Tandem high-dose chemotherapy and autologous stem cell rescue in children with
      newly diagnosed high-risk medulloblastoma or supratentorial primitive neuro
      ectodermic tumors.
AB  - BACKGROUND: To assess the feasibility and effectiveness of high-dose chemotherapy
      (HDC) with stem cell support followed by conventional craniospinal radiotherapy
      (RT) as treatment for children older than 5 years of age with newly diagnosed
      high-risk medulloblastoma (MB) or supratentorial PNET (sPNET). PROCEDURE: Between
      May 2001 and April 2010, 24 children older than 5 years of age (MB = 21; sPNET =
      3), fulfilling inclusion criteria at diagnosis, were treated at Gustave Roussy.
      After conventional chemotherapy, they received two courses of high-dose thiotepa
      (600 mg/m(2)) followed by craniospinal RT. RESULTS: The median follow-up was 4.4
      years (range, 0.8-11.3 years). For children with metastatic MB, the 5-year event
      free survival (EFS) and overall survival (OS) were 72% and 83%, respectively. The
      toxicity was manageable. No toxic death occurred. At the most recent evaluation,
      among the 24 children who had at least one Full Scale Intellectual Quotient
      (FSIQ) examination at a median follow-up of 3.79 years after diagnosis, the mean
      estimated FSIQ was 82 (range, 56-114). CONCLUSIONS: In children with metastatic
      MB, tandem HDCT with ASCT followed by conventional craniospinal RT proved its
      feasibility without jeopardizing survival.

PMID- 24664938
TI  - Histometric analysis and topographic characterization of cp Ti implants with
      surfaces modified by laser with and without silica deposition.
AB  - Biologic behavior of the bone tissue around implants with four different surfaces
      was evaluated. The surfaces were: modified by laser (LS); modified by laser with
      sodium silicate deposition (SS); and commercially available surfaces modified by
      acid etching (AS) and machined surface (MS). Topographic characterization of the
      surfaces was performed by scanning electron microscopy (SEM)- energy dispersive X
      ray spectrometry (EDX) before experimental surgery. Thirty rabbits received 60
      implants in their right and left tibias, 1 implant of each surface being placed
      in each tibia. The analyzed periods were 4, 8, and 12 weeks postoperatively.
      Histometric analysis was performed evaluating bone interface contact (BIC) and
      bone area (BA). The results obtained were submitted to the analysis of variance
      and the Tukey t-test. The elemental mapping was evaluated by means of SEM at 4
      weeks postoperatively. The topographic characterization showed differences
      between the analyzed surfaces. Generally, the BIC and BA of LS and SS implants
      were statistically higher than those of AS and MS in most of the analyzed
      periods. Elemental mapping showed high peaks of calcium and phosphorous in all
      groups. Based on the present methodology, it may be concluded that experimental
      modifications LS and SS accelerated the stages of the bone tissue repair process
      around the implants, providing the highest degree of osseointegration.

PMID- 24664940
TI  - [Moral appeals to donate organs undermine trust].

PMID- 24664939
TI  - Impact of chemotherapy-induced alopecia distress on body image, psychosocial well
      being, and depression in breast cancer patients.
AB  - PURPOSE: This study aims to evaluate the impact of chemotherapy-induced alopecia
      (CIA) distress on body image, psychosocial well-being, and depression among
      breast cancer patients. METHODS: A cross-sectional survey was conducted at the
      breast cancer advocacy events held at 16 hospitals in Korea. Alopecia distress
      was assessed using the 'Chemotherapy-Induced Alopecia Distress Scale', body image
      and psychosocial well-being were measured by the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and breast
      specific module (BR23), and depression was measured using the Center for
      Epidemiological Studies Depression scale. Means of outcomes were compared between
      low and high CIA distress groups. Univariable and multivariable linear regression
      models were used to analyze the relationship between the CIA distress and body
      image, psychosocial well-being, and depression. RESULTS: One hundred sixty-eight
      breast cancer patients participated in the study; the mean age was 48.4 (SD =
      8.4) years, and 55.3% of the patients experienced higher distress from alopecia.
      In fully adjusted models, the high distress group was more likely to have a
      poorer body image than the low distress group (35.2 vs. 62.0; p < 0.001).
      Distressed patients were also more likely to report lower emotional (55.3 vs.
      76.9; p < 0.001), role (58.6 vs. 72.0; p < 0.001), and social functioning (51.3
      vs. 70.9; p < 0.001). The high distress group was also more likely to have
      depression compared with the low distress group (19.6 vs. 14.8; p < 0.001).
      CONCLUSIONS: Chemotherapy-induced alopecia distress was negatively associated
      with body image, psychosocial well-being, and depression in women with breast
      cancer. It is necessary to develop specific interventions to minimize distress
      due to alopecia for women with breast cancer.

PMID- 24664941
TI  - [Moral appeals to donate organs undermine trust].

PMID- 24664942
TI  - [Moral appeals to donate organs undermine trust].

PMID- 24664943
TI  - [Moral appeals to donate organs undermine trust].

PMID- 24664944
TI  - Rapid progression of anemia related to tumor-lysis syndrome associated with
      bortezomib treatment in myeloma patients.
AB  - OBJECTIVE: Tumor-lysis syndrome is a rare complication in patients with multiple
      myeloma. However, bortezomib treatment for myeloma is often associated with tumor
      lysis syndrome. METHODS: We developed an index called the rapid anemia
      progression index, which represents the duration and progression of anemia, to
      evaluate risk factors for tumor-lysis syndrome. We retrospectively reviewed 35
      relapsed or refractory myeloma patients treated with bortezomib-containing
      treatment in our institution. We analyzed various parameters, including albumin,
      lactase dehydrogenase, beta2-microglobulin and creatinine, similar to the rapid
      anemia progression index, and evaluated the risk factors for tumor-lysis syndrome
      associated with bortezomib by the Cairo-Bishop definition. RESULTS: Clinical
      tumor-lysis syndrome occurred in six patients (17.1%). Tumor-lysis syndrome
      occurred during the first course of bortezomib-containing treatment among all the
      patients. The result of the area under the receiver operating characteristic
      curve for the rapid anemia progression index was 0.759 (P = 0.049). The rapid
      anemia progression index was more accurate than the index of lactate
      dehydrogenase, beta2-microglobulin, albumin and creatinine according to the
      receiver operating characteristic curve. For a cut-off point of -1.12 for the
      rapid anemia progression index, the sensitivity and specificity were 66.7 and
      82.8%, respectively. CONCLUSIONS: The rapid anemia progression index is related
      to clinical tumor-lysis syndrome associated with bortezomib treatment for
      multiple myeloma patients with a cut-off point of -1.12 g/dl/month.

PMID- 24664945
TI  - Trivascular coronary artery ectasia: challenging hybrid PET/CT myocardial blood
      flow measurement.

PMID- 24664947
TI  - Glutamate quantification in patients with supratentorial gliomas using chemical
      shift imaging.
AB  - This study aimed to evaluate and validate chemical shift imaging (CSI) for in
      vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If
      validated, CSI could become an extremely useful tool to investigate metabolic
      dysfunction of Glu in excitotoxic neuropathologies. Quantitative CSI estimates of
      Glu concentrations were compared with known concentrations of Glu in aqueous
      phantom solutions. Forty-one patients with known or likely supratentorial gliomas
      underwent preoperative CSI. The spectra obtained were analyzed for Glu
      concentrations and Glu to creatine (Cr) ratios. These in vivo measurements were
      correlated against ex vivo Glu content quantified by high performance liquid
      chromatography (HPLC) measured in 65 resected brain tumor and peritumoral brain
      specimens. For the phantom solutions the CSI estimates of Glu concentration and
      the Glu/Cr ratios were highly correlated with known Glu concentration (r2  =
      0.95, p = 0.002, and r2  = 0.97, p < 0.0001, respectively). There was a modest,
      but statistically significant, correlation between the ex vivo measured Glu and
      in vivo spectroscopic Glu concentration (r2  = 0.22, p = 0.04) and ratios of Glu
      to Cr (r2  = 0.30, p = 0.002). Quantitative measurement of Glu content is
      feasible in patients with supratentorial gliomas using CSI. The in vitro and in
      vivo results suggest that this has the potential to be a reliable quantitative
      imaging assay for brain tumor patients. This may have wide clinical research
      applications in a number of neurological disorders where Glu excitotoxicity and
      metabolic dysfunction are known to play a role in pathogenesis, including tumor
      associated epilepsy, epilepsy, stroke and neurotrauma.

PMID- 24664948
TI  - Circadian rhythm characteristics, poor sleep quality, daytime sleepiness and
      common psychiatric disorders among Thai college students.
AB  - INTRODUCTION: To investigate the relationship between common psychiatric
      disorders (CPDs) and sleep characteristics (evening chronotype, poor sleep
      quality and daytime sleepiness) among Thai college students. METHODS: A cross
      sectional study was conducted among 2,970 undergraduate students in Thailand.
      Students were asked to complete a self-administered questionnaire that collected
      information about lifestyle and demographic characteristics. The Horne and
      Ostberg Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality
      Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate circadian
      preference, sleep quality and daytime sleepiness, respectively. The General
      Health Questionnaire-12 (GHQ-12) was used to evaluate presence of CPDs. Logistic
      regression models were used to estimate adjusted odds ratios (ORs) and 95%
      confidence intervals (95% CIs) of CPDs in relation to the covariates of interest.
      RESULTS: A total of 337 students were classified as having CPDs (11.2%; 95% CI
      10.1-12.3%). Evening chronotype (OR = 3.35; 95% CI 2.09-5.37), poor sleep quality
      (OR = 4.89; 95% CI 3.66-6.54) and excessive daytime sleepiness (OR = 1.95; 95% CI
      1.54-2.47) were statistically significantly associated with CPDs. DISCUSSION: Our
      study demonstrated that CPDs are common among Thai college students. Further,
      evening chronotype, poor sleep quality and excessive daytime sleepiness were
      strongly associated with increased risk of CPDs. These findings highlight the
      importance of educating students and school administrators about the importance
      of sleep and their impact on mental health.

PMID- 24664949
TI  - Composite mapping experiences in airborne gamma spectrometry.
AB  - During an international intercomparison exercise of airborne gamma spectrometry
      held in Switzerland 2007 teams from Germany, France and Switzerland were proving
      their capabilities. One of the tasks was the composite mapping of an area around
      Basel. Each team was mainly covering the part of its own country at its own
      flying procedures. They delivered the evaluated data in a data format agreed in
      advance. The quantities to be delivered were also defined in advance.
      Nevertheless, during the process to put the data together a few questions raised:
      Which dose rate was meant? Had the dose rate to be delivered with or without
      cosmic contribution? Activity per dry or wet mass? Which coordinate system was
      used? Finally, the data could be put together in one map. For working procedures
      in case of an emergency, quantities of interest and exchange data format have to
      be defined in advance. But the procedures have also to be proved regularly. 

PMID- 24664950
TI  - A 1-year study of endurance runners: training, laboratory tests, and field tests.
AB  - PURPOSE: To examine the training and concomitant changes in laboratory- and field
      test performance of highly trained endurance runners. METHODS: Fourteen highly
      trained male endurance runners (mean +/- SD maximal oxygen uptake [VO2max] 69.8
      +/- 6.3 mL . kg-1 . min-1) completed this 1-y training study commencing in April.
      During the study the runners undertook 5 laboratory tests of VO2max, lactate
      threshold (LT), and running economy and 9 field tests to determine critical speed
      (CS) and the modeled maximum distance performed above CS (D'). The data for
      different periods of the year were compared using repeated-measures ANOVA. The
      influence of training on laboratory- and field-test changes was analyzed by
      multiple regression. RESULTS: Total training distance varied during the year and
      was lower in May-July (333 +/- 206 km, P = .01) and July-August (339 +/- 206 km,
      P = .02) than in the subsequent January-February period (474 +/- 188 km). VO2max
      increased from the April baseline (4.7 +/- 0.4 L/min) in October and January
      periods (5.0 +/- 0.4 L/min, P <= .01). Other laboratory measures did not change.
      Runners' CS was lowest in August (4.90 +/- 0.32 m/s) and highest in February
      (4.99 +/- 0.30 m/s, P = .02). Total training distance and the percentage of
      training time spent above LT velocity explained 33% of the variation in CS.
      CONCLUSION: Highly trained endurance runners achieve small but significant
      changes in VO2max and CS in a year. Increases in training distance and time above
      LT velocity were related to increases in CS.

PMID- 24664951
TI  - Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4
      plasma membrane translocation.
AB  - Grb10 is an intracellular adaptor protein which binds directly to several growth
      factor receptors, including those for insulin and insulin-like growth factor
      receptor-1 (IGF-1), and negatively regulates their actions. Grb10-ablated (Grb10(
      /-) ) mice exhibit improved whole body glucose homeostasis and an increase in
      muscle mass associated specifically with an increase in myofiber number. This
      suggests that Grb10 may act as a negative regulator of myogenesis. In this study,
      we investigated in vitro, the molecular mechanisms underlying the increase in
      muscle mass and the improved glucose metabolism. Primary muscle cells isolated
      from Grb10(-/-) mice exhibited increased rates of proliferation and
      differentiation compared to primary cells isolated from wild-type mice. The
      improved proliferation capacity was associated with an enhanced phosphorylation
      of Akt and ERK in the basal state and changes in the expression of key cell cycle
      progression markers involved in regulating transition of cells from the G1 to S
      phase (e.g., retinoblastoma (Rb) and p21). The absence of Grb10 also promoted a
      faster transition to a myogenin positive, differentiated state. Glucose uptake
      was higher in Grb10(-/-) primary myotubes in the basal state and was associated
      with enhanced insulin signaling and an increase in GLUT4 translocation to the
      plasma membrane. These data demonstrate an important role for Grb10 as a link
      between muscle growth and metabolism with therapeutic implications for diseases,
      such as muscle wasting and type 2 diabetes.

PMID- 24664952
TI  - The multidimensional sensation of desire to void differs between people with and
      without overactive bladder.
AB  - AIM: To determine whether the multidimensional sensation of desire to void can be
      reliability assessed and whether differences exist between people with and
      without overactive bladder (OAB). Assessing reliability and convergent validity
      of OAB screening tools comprised a secondary aim. METHODS: This observational,
      repeated-measures study involved 64 volunteers (47 female), aged >=50 years, with
      and without OAB symptoms. Six sensory dimensions (intensity, unpleasantness,
      suddenness, perceived difficulty "holding on," bladder fullness and location of
      sensation) were assessed by structured interview on two occasions. Overactive
      bladder status was determined using the OAB Symptom Score and OAB Awareness Tool.
      Reliability of sensory dimensions was assessed via random effects mixed modeling.
      The ability of each sensory dimension to predict OAB status was determined by
      partial least squares regression. RESULTS: With the exception of sensory
      intensity, perceived bladder fullness, and one location of sensation, sensory
      dimensions were reliably reported. Sensory intensity, unpleasantness, suddenness,
      and perceived difficulty "holding on" predicted OAB, whereas perceived bladder
      fullness and sensory location did not. The OAB screening questionnaires
      demonstrated comparable test-retest reliability and convergent validity.
      CONCLUSIONS: People with and without OAB can reliably describe the
      multidimensional sensation of desire to void. The sensation of desire to void is
      more intense, unpleasant, sudden, and perceived as more difficult to hold on in
      people with OAB.

PMID- 24664953
TI  - Properties of dehydrated human amnion/chorion composite grafts: Implications for
      wound repair and soft tissue regeneration.
AB  - PURION((r)) processed dehydrated human amnion/chorion membrane (dHACM; MiMedx
      Group, Marietta, GA) tissue products were analyzed for the effectiveness of the
      PURION((r)) process in retaining the native composition of the amniotic membrane
      and preserving bioactivity in the resulting products. dHACM was analyzed for
      extracellular matrix (ECM) composition through histological staining and for
      growth factor content via multiplex ELISA arrays. Bioactivity was assessed by
      evaluating endogenous growth factor production by human dermal fibroblasts in
      response to dHACM and for thermal stability by mechanical tests and in vitro cell
      proliferation assays. Histology of dHACM demonstrated preservation of the native
      amnion and chorion layers with intact, nonviable cells, collagen, proteoglycan,
      and elastic fibers distributed in the individual layers. An array of 36 cytokines
      known to regulate processes involved in inflammation and wound healing were
      identified in dHACM. When treated with dHACM extracts, bioactivity was
      demonstrated through an upregulation of basic fibroblast growth factor,
      granulocyte colony-stimulating factor, and placental growth factor biosynthesis,
      three growth factors involved in wound healing, by dermal fibroblasts in vitro.
      After conditioning at temperatures ranging from -78.7 to +73.5 degrees C, dHACM
      retained its tensile strength and ability to promote proliferation of dermal
      fibroblasts in vitro. Elution experiments demonstrated a soluble fraction of
      growth factors that eluted from the tissue and another fraction sequestered
      within the matrix. The PURION((r)) process retains the native composition of ECM
      and signaling molecules and preserves bioactivity. The array of cytokines
      preserved in dHACM are in part responsible for its therapeutic efficacy in
      treating chronic wounds by orchestrating a "symphony of signals" to promote
      healing.

PMID- 24664954
TI  - Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil
      lymphoid tissue; evidence for poor immune cell infiltration into devil facial
      tumors.
AB  - The Tasmanian devil is under threat of extinction due to the transmissible devil
      facial tumor disease (DFTD). This fatal tumor is an allograft that does not
      induce an immune response, raising questions about the activity of Tasmanian
      devil immune cells. T and B cell analysis has been limited by a lack of
      antibodies, hence the need to produce such reagents. Amino acid sequence analysis
      revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials.
      Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating
      bacterial fusion proteins. These, and commercial antibodies against CD1a and
      CD83, identified T cells, B cells and dendritic cells by immunohistochemistry.
      CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph
      nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical
      distribution was characteristic of mammalian lymphoid tissues with more CD4(+)
      than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B
      cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid
      tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells.
      Dendritic cells were identified in lymph node, spleen and skin. This distribution
      is consistent with eutherian mammals and other marsupials, indicating they have
      the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease
      tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were
      also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or
      IgG(+) B cells, consistent with poor immune cell infiltration.

PMID- 24664956
TI  - Synthesis of cyano-substituted diaryltetracenes from tetraaryl[3]cumulenes.
AB  - A versatile, two-step synthesis of highly substituted, cyano-functionalized
      diaryltetracenes has been developed, starting from easily accessible
      tetraaryl[3]cumulenes. This unprecedented transformation is initiated by [2+2]
      cycloaddition of tetracyanoethylene (TCNE) to the proacetylenic central double
      bond of the cumulenes to give an intermediate zwitterion, which after an
      electrocyclization cascade and dehydrogenation yields 5,5,11,11-tetracyano-5,11
      dihydrotetracenes in a one-pot procedure. A subsequent copper-assisted
      decyanation/aromatization provided the target 5,11-dicyano-6,12-diaryltetracene
      derivatives. All of the postulated structures were confirmed by X-ray
      crystallography. The new chromophores are thermally highly stable and feature
      promising fluorescence properties for potential use in optoelectronic devices.
      They are selective chemosensors for Cu(I) ions, which coordinate to one of the CN
      substituents and form a 1:1 complex with an association constant of Ka =1.5*10(5)
      L mol(-1) at 298 K. 

PMID- 24664955
TI  - A phase I trial of MK-2206 in children with refractory malignancies: a Children's
      Oncology Group study.
AB  - BACKGROUND: We report results of a phase I trial designed to estimate the maximum
      tolerated dose (MTD), describe dose-limiting toxicities (DLT), and characterize
      the pharmacokinetic profile of MK-2206, an AKT inhibitor, in children with
      refractory or recurrent malignancies. PROCEDURE: MK-2206 was administered either
      every other day (Schedule 1), or once a week (Schedule 2) in a 28-day cycle. Dose
      escalations in increments of ~30% were independently made in each part using the
      rolling-six design. Serial pharmacokinetic (PK) studies were obtained. Biological
      studies include analysis of PI3K/PTEN/AKT-cell signaling pathway in pre and post
      therapy in PBMC and in tumors at diagnosis or recurrence. RESULTS: Fifty patients
      (26 males, median age 12.6 years [range, 3.1-21.9]) with malignant glioma (16),
      ependymoma (4), hepatocellular carcinoma (3), gliomatosis cereberi (2), or other
      tumors (22) were enrolled; 40 were fully evaluable for toxicity (Schedule 1, n =
      23; Schedule 2, n = 17). Schedule 1 DLTs included: grade 3 dehydration in 1/6
      patients at 28 mg/m(2) ; grade 4 hyperglycemia and neutropenia in 1/6 patients at
      45 mg/m(2) ; and grade 3 rash in 3/6 patients at dose level 4 (58 mg/m(2) ).
      Schedule 2 DLTs included: grade 3 alkaline phosphatase in 1/6 patients at 90
      mg/m(2) ; grade 3 rash in 1/6 patients at 120 mg/m(2) ; and grade 3 rash in 2/6
      patients at 155 mg/m(2) . CONCLUSIONS: The recommended pediatric phase 2 dose of
      MK-2206 is 45 mg/m(2) /dose every other day or 120 mg/m(2) /dose weekly. PK
      appeared linear over the dose range studied.

PMID- 24664957
TI  - [One health, one world].

PMID- 24664958
TI  - Psychological distress and unsatisfied need for psychosocial support in
      adolescent and young adult cancer patients during the first year following
      diagnosis.
AB  - PURPOSE: Identifying at-risk adolescent and young adult (AYA) cancer patients and
      referring them to age-appropriate psychosocial support services may be
      instrumental in reducing psychological distress and promoting psychosocial
      adaptation. The purpose of this study is to identify trajectories of clinically
      significant levels of distress throughout the first year following diagnosis and
      to distinguish factors, including supportive care service use, that predict the
      extent to which AYAs report distress. METHODS: In this prospective multisite
      study, 215 AYAs aged 15-39 years were assessed for psychological distress and
      psychosocial support service use within the first 4 months of diagnosis and again
      6 and 12 months later. On the basis of distress scores, respondents were assigned
      to one of four distress trajectory groups (Resilient, Recovery, Delayed, and
      Chronic). Multiple logistic regression analyses examined whether demographics,
      clinical variables, and reports of unsatisfied need for psychosocial support were
      associated with distress trajectories over 1 year. RESULTS: Twelve percent of
      AYAs reported clinically significant chronic distress throughout the first 12
      months following diagnosis. An additional 15% reported delayed distress.
      Substantial proportions of AYAs reported that needs for information (57%),
      counseling (41%), and practical support (39%) remained unsatisfied at 12 months
      following diagnosis. Not getting counseling needs met, particularly with regard
      to professional mental health services, was observed to be significantly
      associated with distress over time. CONCLUSIONS: Substantial proportions of AYAs
      are not utilizing psychosocial support services. Findings suggest the importance
      of identifying psychologically distressed AYAs and addressing their needs for
      mental health counseling throughout a continuum of care.

PMID- 24664959
TI  - Fast multidimensional NMR spectroscopy for sparse spectra.
AB  - Multidimensional NMR spectroscopy is widely used for studies of molecular and
      biomolecular structure. A major disadvantage of multidimensional NMR is the long
      acquisition time which, regardless of sensitivity considerations, may be needed
      to obtain the final multidimensional frequency domain coefficients. In this
      article, a method for under-sampling multidimensional NMR acquisition of sparse
      spectra is presented. The approach is presented in the case of two-dimensional
      NMR acquisitions. It relies on prior knowledge about the support in the two
      dimensional frequency domain to recover an over-determined system from the under
      determined system induced in the linear acquisition model when under-sampled
      acquisitions are performed. This over-determined system can then be solved with
      linear least squares. The prior knowledge is obtained efficiently at a low cost
      from the one-dimensional NMR acquisition, which is generally acquired as a first
      step in multidimensional NMR. If this one-dimensional acquisition is
      intrinsically sparse, it is possible to reconstruct the corresponding two
      dimensional acquisition from far fewer observations than those imposed by the
      Nyquist criterion, and subsequently to reduce the acquisition time. Further
      improvements are obtained by optimizing the sampling procedure for the least
      squares reconstruction using the sequential backward selection algorithm.
      Theoretical and experimental results are given in the case of a traditional
      acquisition scheme, which demonstrate reliable and fast reconstructions with
      acceleration factors in the range 3-6. The proposed method outperforms the CS
      methods (OMP, L1) in terms of the reconstruction performance, implementation and
      computation time. The approach can be easily extended to higher dimensions and
      spectroscopic imaging.

PMID- 24664960
TI  - Emergence of Klebsiella pneumoniae liver abscesses in South-western Sydney.

PMID- 24664963
TI  - Phenotype of a patient with contiguous deletion of TBX5 and TBX3: expanding the
      disease spectrum.
AB  - The important roles that T-box genes play in the morphogenesis of the heart and
      its conduction system has long been established, and a number of disorders are
      linked to mutations in these T-box genes. Holt-Oram syndrome (HOS), the classic
      heart and hand syndrome, is clinically typified by radial ray upper limb
      abnormalities and cardiac malformations, and is caused by mutations involving
      TBX5. Another member of the T-box gene family, TBX3, is found in close proximity
      to TBX5 on chromosome 12q24. Mutations in TBX3 cause ulnar-mammary syndrome
      (UMS), which is distinguished by upper limb malformations affecting the ulnar
      ray, apocrine, and mammary gland hypoplasia, and genital defects. While disorders
      involving isolated mutations of TBX5 and TBX3 have been well described,
      contiguous deletions of these T-box genes remain exceptional. We report on a
      patient with features of both HOS and UMS consisting of bilateral symmetric limb
      malformations, congenital cardiac defects, and rapidly progressive cardiac
      conduction disease.

PMID- 24664962
TI  - Raynaud's phenomenon, inflammatory arthritis, and weight loss: pay attention to
      the man behind the curtain.

PMID- 24664964
TI  - The extent of ligament injury and its influence on pelvic stability following
      type II anteroposterior compression pelvic injuries--A computer study to gain
      insight into open book trauma.
AB  - Surgical stabilization of the pelvis following type II anteroposterior
      compression pelvic injuries (APCII) is based on the assumption that the anterior
      sacroiliac, sacrospinous, and sacrotuberous ligaments disrupt simultaneously.
      Recent data on the ligaments contradict this concept. We aimed at determining the
      mechanisms of ligament failure in APCII computationally. In an individual
      osteoligamentous computer model of the pelvis, ligament load, and strain were
      observed for the two-leg stance, APCII with 100-mm symphyseal widening and for
      two-leg stance with APCII-related ligament failure, and validated with body
      donors. The anterior sacroiliac and sacrotuberous ligaments had the greatest load
      with 80% and 17% of the total load, respectively. APCII causes partial failure of
      the anterior sacroiliac ligament and the pelvis to become horizontally instable.
      The other ligaments remained intact. The sacrospinous ligament was negligibly
      loaded but stabilized the pelvis vertically. The interosseous sacroiliac and
      sacrotuberous ligaments are likely responsible for reducing the symphysis and
      might serve as an indicator of vertical stability. The sacrospinous ligament
      appears to be of minor significance in APCII but plays an important role in
      vertical stabilization. Further research is necessary to determine the influence
      of alterations in ligament and bone material properties.

PMID- 24664965
TI  - Jumping and hopping in elite and amateur orienteering athletes and correlations
      to sprinting and running.
AB  - PURPOSE: Jumping and hopping are used to measure lower-body muscle power,
      stiffness, and stretch-shortening-cycle utilization in sports, with several
      studies reporting correlations between such measures and sprinting and/or running
      abilities in athletes. Neither jumping and hopping nor correlations with
      sprinting and/or running have been examined in orienteering athletes. METHODS:
      The authors investigated squat jump (SJ), countermovement jump (CMJ), standing
      long jump (SLJ), and hopping performed by 8 elite and 8 amateur male foot
      orienteering athletes (29 +/- 7 y, 183 +/- 5 cm, 73 +/- 7 kg) and possible
      correlations to road, path, and forest running and sprinting performance, as well
      as running economy, velocity at anaerobic threshold, and peak oxygen uptake
      (VO(2peak)) from treadmill assessments. RESULTS: During SJs and CMJs, elites
      demonstrated superior relative peak forces, times to peak force, and prestretch
      augmentation, albeit lower SJ heights and peak powers. Between-groups differences
      were unclear for CMJ heights, hopping stiffness, and most SLJ parameters. Large
      pairwise correlations were observed between relative peak and time to peak forces
      and sprinting velocities; time to peak forces and running velocities; and
      prestretch augmentation and forest-running velocities. Prestretch augmentation
      and time to peak forces were moderately correlated to VO(2peak). Correlations
      between running economy and jumping or hopping were small or trivial.
      CONCLUSIONS: Overall, the elites exhibited superior stretch-shortening-cycle
      utilization and rapid generation of high relative maximal forces, especially
      vertically. These functional measures were more closely related to sprinting
      and/or running abilities, indicating benefits of lower-body training in
      orienteering.

PMID- 24664966
TI  - Ultra-uniform SnOx/carbon nanohybrids toward advanced lithium-ion battery anodes.

PMID- 24664967
TI  - Free energy calculations, enhanced by a Gaussian ansatz, for the "chemical work"
      distribution.
AB  - The evaluation of the free energy is essential in molecular simulation because it
      is intimately related with the existence of multiphase equilibrium. Recently, it
      was demonstrated that it is possible to evaluate the Helmholtz free energy using
      a single statistical ensemble along an entire isotherm by accounting for the
      "chemical work" of transforming each molecule, from an interacting one, to an
      ideal gas. In this work, we show that it is possible to perform such a free
      energy perturbation over a liquid vapor phase transition. Furthermore, we
      investigate the link between a general free energy perturbation scheme and the
      novel nonequilibrium theories of Crook's and Jarzinsky. We find that for finite
      systems away from the thermodynamic limit the second law of thermodynamics will
      always be an inequality for isothermal free energy perturbations, resulting
      always to a dissipated work that may tend to zero only in the thermodynamic
      limit. The work, the heat, and the entropy produced during a thermodynamic free
      energy perturbation can be viewed in the context of the Crooks and Jarzinsky
      formalism, revealing that for a given value of the ensemble average of the
      "irreversible" work, the minimum entropy production corresponded to a Gaussian
      distribution for the histogram of the work. We propose the evaluation of the free
      energy difference in any free energy perturbation based scheme on the average
      irreversible "chemical work" minus the dissipated work that can be calculated
      from the variance of the distribution of the logarithm of the work histogram,
      within the Gaussian approximation. As a consequence, using the Gaussian ansatz
      for the distribution of the "chemical work," accurate estimates for the chemical
      potential and the free energy of the system can be performed using much shorter
      simulations and avoiding the necessity of sampling the computational costly tails
      of the "chemical work." For a more general free energy perturbation scheme that
      the Gaussian ansatz may not be valid, the free energy calculation can be
      expressed in terms of the moment generating function of the "chemical work"
      distribution.

PMID- 24664968
TI  - Evaluation of bone formation guided by DNA/protamine complex with FGF-2 in an
      adult rat calvarial defect model.
AB  - DNA/protamine complex paste (D/P) and D/P complex paste with Fibroblast Growth
      Factor-2 (FGF-2) (D/P-FGF) were prepared to investigate their new bone formation
      abilities using an ~40-week-old rat calvarial defect model. It was found that D/P
      could release FGF-2 proportionally in an in vitro experiment with an enzyme
      linked immunosorbent assay. It was also found that aging adversely affected self
      bone healing of rats by comparison with the results in a previous study using 10
      week-old rats. Microcomputed tomography and histopathological examinations showed
      that new bone formation abilities of D/P and D/P-FGF were superior to that of the
      control (sham operation). Control, D/P and D/P-FGF showed newly formed bone areas
      of 6.7, 58.3, and 67.0%, respectively, 3 months after the operation. Moreover, it
      was found that FGF-2 could support the osteoanagenesis ability of D/P. It was
      considered that FGF-2 could play an important role in new bone formation at early
      stages because it induced the genes such as collagen I, CBFA, OSX, and OPN, which
      are initiated first in the process of osteogenesis. Therefore, D/P-FGF will be a
      useful injectable biomaterial with biodegradable properties for the repair of
      bone defects in the elderly.

PMID- 24664969
TI  - Fusing N-heterocyclic carbenes with carborane anions.
AB  - Here we describe the fusion of two families of unusual carbon-containing
      molecules that readily disregard the tendency of carbon to form four chemical
      bonds, namely N-heterocyclic carbenes (NHCs) and carborane anions. Deprotonation
      of an anionic imidazolium salt with lithium diisopropylamide at room temperature
      leads to a mixture of lithium complexes of C-2 and C-5 dianionic NHC
      constitutional isomers as well as a trianionic (C-2, C-5) adduct. Judicious
      choice of the base and reaction conditions allows the selective formation of all
      three stable polyanionic carbenes. In solution, the so-called abnormal C-5 NHC
      lithium complex slowly isomerizes to the normal C-2 NHC, and the process can be
      proton-catalyzed by the addition of the anionic imidazolium salt. These results
      indicate that the combination of two unusual forms of carbon atoms can lead to
      unexpected chemical behavior, and that this strategy paves the way for the
      development of a broad new generation of NHC ligands for catalysis. 

PMID- 24664970
TI  - Aggressive variants of follicular cell-derived thyroid carcinomas: a
      cytopathologist's perspective.
AB  - Follicular cell-derived carcinomas of the thyroid gland comprise a heterogeneous
      group of malignant neoplasms of the thyroid gland with varied histologic
      appearance and molecular profiles. In most patients, these tumors represent
      relatively indolent neoplasms; however, certain subtypes/variants behave in an
      aggressive manner, and the recognition of this subset of tumors is essential
      because of their variable response to therapy and significant morbidity and
      mortality. Fine-needle aspiration is considered an essential tool for the
      diagnosis of suspicious thyroid nodules. In this review, the authors discuss the
      clinical, histologic, and molecular findings and the prognostic implications of
      aggressive thyroid neoplasms with emphasis on the characteristic cytomorphologic
      features on fine-needle aspiration smears.

PMID- 24664971
TI  - HIF-1alpha- and hypoxia-dependent immune responses in human CD4+CD25high T cells
      and T helper 17 cells.
AB  - The central oxygen sensitive transcription factor HIF-1alpha has been implicated
      in the differentiation of n(T(reg)) and Th17 cells and to orchestrate metabolic
      changes of activated T cells. However, data on the functional relevance of HIF
      1alpha and Hox, in general, for nT(reg)-suppressive activity and T cell function
      in primary human cells are still missing. Therefore, we analyzed the effect of
      Hox and HIF-1alpha on human T(res), n(Treg), and Th17 cells. Under Hox, nT(reg)
      mediated suppression of T(res) proliferation, CD25 expression, and secretion of
      IFN-gamma were significantly reduced, whereas expression levels of VEGF, TNF
      alpha, and IL-10 were significantly increased. In contrast to observations in
      mice, Th17 lineage commitment, as determined by RORgammat expression, was not
      affected by activation or inhibition of HIF-1alpha expression using DMOG or YC-1
      treatment, respectively. Nevertheless, the secretion of IL-17A was increased by
      DMOG and reduced by YC-1 under Th17-skewing conditions in a dose- dependent
      manner. In conclusion, Hox and HIF-1alpha substantially influence human T cell
      mediated immune responses by modulation of nT(reg)-suppressive function and IL
      17A secretion by Th17 cells.

PMID- 24664972
TI  - The startle paradigm in a forensic psychiatric setting: elucidating psychopathy.
AB  - BACKGROUND: Most people who meet the diagnostic criteria for anti-social
      personality disorder (ASPD) do not meet the criteria for psychopathy. A
      differentiating feature is affective-interpersonal style. Eye blink startle
      reflex paradigms have been used to study affect. AIM: The aim of this study is to
      explore an eye blink startle paradigm as a means of distinguishing between men
      with both ASPD and psychopathy, and men with ASPD alone. METHODS: One hundred and
      thirty-six men were recruited as follows: 31 patients with ASPD and a Psychopathy
      Checklist-Revised (PCL-R) score of 26 or more, 22 patients with ASPD and a PCL-R
      score of 25 or less, 50 forensic hospital employees and 33 general population
      men, none in the latter two groups having abnormal personality traits. Each was
      presented with 16 pleasant, 16 unpleasant and 16 neutral pictures. Acoustic
      probes were presented during each category at 300, 800, 1300 and 3800
      milliseconds (ms) after picture onset. Eye blink response was measured by
      electromyography. RESULTS: Overall, both patient groups showed significantly
      smaller eye blink responses to the startle stimuli compared with the community
      controls. Both the latter and the ASPD group showed the expected increase in eye
      blink response at longer startle latencies to unpleasant pictures than pleasant
      pictures, but this was not present either in the group with psychopathy or in the
      forensic hospital employees. With increasing startle latency onset, eye blink
      amplitude increased significantly in both the healthy comparison groups and the
      ASPD group, but not in the group with psychopathy. CONCLUSIONS: We replicated eye
      blink startle modulation deficiencies among men with psychopathy. We confirmed
      that the psychopathy and ASPD groups could be distinguished by startle stimulus
      onset asynchrony, but this pattern was also seen in one healthy group - the
      forensic hospital employees. This suggests a case for more research with more
      diverse comparison groups and more differentiation of personality traits before
      drawing definitive conclusions about distinctive startle response patterns among
      men with psychopathy.

PMID- 24664974
TI  - [Syllabus neuropediatrics structures, quality and perspectives of outpatient,
      inpatient and rehabilitative care version 2.0 (part 1)].

PMID- 24664975
TI  - N-cadherin/wnt interaction controls bone marrow mesenchymal cell fate and bone
      mass during aging.
AB  - Age-related bone loss is characterized by reduced osteoblastogenesis and
      excessive bone marrow adipogenesis. The mechanisms governing bone marrow
      mesenchymal stromal cell (BMSC) differentiation into adipocytes or osteoblasts
      during aging are unknown. We show here that overexpressing N-cadherin (Cadh2) in
      osteoblasts increased BMSC adipocyte differentiation and reduced osteoblast
      differentiation in young transgenic (Tg) mice whereas this phenotype was fully
      reversed with aging. The reversed phenotype with age was associated with enhanced
      Wnt5a and Wnt10b expression in osteoblasts and a concomitant increase in BMSC
      osteogenic differentiation. Consistent with this mechanism, conditioned media
      from young wild type osteoblasts inhibited adipogenesis and promoted osteoblast
      differentiation in BMSC from old Cadh2 Tg mice, and this response was abolished
      by Wnt5a and Wnt10b silencing. Transplantation of BMSC from old Cadh2 Tg mice
      into young Tg recipients increased Wnt5a and Wnt10b expression and rescued BMSC
      osteogenic differentiation. In senescent osteopenic mice, blocking the CADH2-Wnt
      interaction using an antagonist peptide increased Wnt5a and Wnt10b expression,
      bone formation, and bone mass. The data indicate that Cadh2/Wnt interaction in
      osteoblasts regulates BMSC lineage determination, bone formation, and bone mass
      and suggest a therapeutic target for promoting bone formation in the aging
      skeleton.

PMID- 24664976
TI  - Local area cartilage segmentation: a semiautomated novel method of measuring
      cartilage loss in knee osteoarthritis.
AB  - OBJECTIVE: To assess the responsiveness and reader time of a novel semiautomated
      tool to detect knee cartilage loss over 2 years in subjects with knee
      osteoarthritis. METHODS: A total of 122 subjects from the Osteoarthritis
      Initiative progression cohort were selected. A reader used the software method to
      segment cartilage on double-echo steady-state sequence scans in the medial
      compartment of the femur from the baseline and 24-month visits. Change in
      cartilage volume (DeltaV) was measured at a fixed weight-bearing (WB) location
      with respect to the 3-dimensional coordinate system based on cylindrical
      coordinates. Change was measured for 5 regions of varying WB surface area
      centered on the fixed point. The average change (DeltaV), the SD of DeltaV, and
      the standardized response mean (SRM) are reported. RESULTS: The SRM was -0.52 for
      the largest region and decreased in magnitude as smaller regions of cartilage
      were probed. The average evaluation time was <20 minutes per knee compartment,
      split approximately evenly between a technician and a trained reader. CONCLUSION:
      The results establish that measurement of cartilage loss in a local region can be
      done efficiently and that the resultant measures are responsive to loss of
      cartilage over time. The coordinate system can potentially be used to objectively
      examine and establish a consistent location for all knees that is most responsive
      to change in cartilage volume. This technique can provide rapidly an objective
      quantitative measure of cartilage loss and could substantially reduce study costs
      for large trials and data sets.

PMID- 24664979
TI  - Challenges of classifying double outlet right ventricle: importance for genotype
      phenotype analyses.

PMID- 24664977
TI  - Systematic prioritization and integrative analysis of copy number variations in
      schizophrenia reveal key schizophrenia susceptibility genes.
AB  - Schizophrenia is a common mental disorder with high heritability and strong
      genetic heterogeneity. Common disease-common variants hypothesis predicts that
      schizophrenia is attributable in part to common genetic variants. However, recent
      studies have clearly demonstrated that copy number variations (CNVs) also play
      pivotal roles in schizophrenia susceptibility and explain a proportion of missing
      heritability. Though numerous CNVs have been identified, many of the regions
      affected by CNVs show poor overlapping among different studies, and it is not
      known whether the genes disrupted by CNVs contribute to the risk of
      schizophrenia. By using cumulative scoring, we systematically prioritized the
      genes affected by CNVs in schizophrenia. We identified 8 top genes that are
      frequently disrupted by CNVs, including NRXN1, CHRNA7, BCL9, CYFIP1, GJA8, NDE1,
      SNAP29, and GJA5. Integration of genes affected by CNVs with known schizophrenia
      susceptibility genes (from previous genetic linkage and association studies)
      reveals that many genes disrupted by CNVs are also associated with schizophrenia.
      Further protein-protein interaction (PPI) analysis indicates that protein
      products of genes affected by CNVs frequently interact with known schizophrenia
      associated proteins. Finally, systematic integration of CNVs prioritization data
      with genetic association and PPI data identifies key schizophrenia candidate
      genes. Our results provide a global overview of genes impacted by CNVs in
      schizophrenia and reveal a densely interconnected molecular network of de novo
      CNVs in schizophrenia. Though the prioritized top genes represent promising
      schizophrenia risk genes, further work with different prioritization methods and
      independent samples is needed to confirm these findings. Nevertheless, the
      identified key candidate genes may have important roles in the pathogenesis of
      schizophrenia, and further functional characterization of these genes may provide
      pivotal targets for future therapeutics and diagnostics. 

PMID- 24664980
TI  - Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention,
      and clinical relevance.
AB  - Nitrate therapy has been an effective treatment for ischemic heart disease for
      over 100 years. The anti-ischemic and exercise-promoting benefits of sublingually
      administered nitrates are well established. Nitroglycerin is indicated for the
      relief of an established attack of angina and for prophylactic use, but its
      effects are short lived. In an effort to increase the duration of beneficial
      effects, long-acting orally administered and topical applications of nitrates
      have been developed; however, following their continued or frequent daily use,
      patients soon develop tolerance to these long-acting nitrate preparations. Once
      tolerance develops, patients begin losing the protective effects of the long
      acting nitrate therapy. By providing a nitrate-free interval, or declining
      nitrate levels at night, one can overcome or reduce the development of tolerance,
      but cannot provide 24-h anti-anginal and anti-ischemic protection. In addition,
      patients may be vulnerable to occurrence of rebound angina and myocardial
      ischemia during periods of absent nitrate levels at night and early hours of the
      morning, and worsening of exercise capacity prior to the morning dose of the
      medication. This has been a concern with nitroglycerin patches but not with oral
      formulations of isosorbide-5 mononitrates, and has not been adequately studied
      with isosorbide dinitrate. This paper describes problems associated with nitrate
      tolerance, reviews mechanisms by which nitrate tolerance and loss of efficacy
      develop, and presents strategies to avoid nitrate tolerance and maintain efficacy
      when using long-acting nitrate formulations. 

PMID- 24664982
TI  - Pacing by winners of a 161-km mountain ultramarathon.
AB  - PURPOSE: To examine pacing among the most successful runners in the 161-km
      Western States Endurance Run (WSER) to determine if variations in segmental speed
      relate to performance, ambient temperature, and calendar year. METHODS: Segmental
      speed and coefficient of variation (CV) in speed were analyzed for 10 race
      segments of 24 races from 1985 through 2013. RESULTS: Segmental speeds did not
      differ between the eventual winners and lead runners and only differed between
      the 1st and 2nd finishers in the 2nd half of the race. Mean CV in speed was lower
      (P < .01) for the winners (12%) than for the other top-5 finishers (14-15%). CV
      in speed was related (r = .80, P = .006) to finish time for the fastest 10 finish
      times at the WSER. Multiple linear-regression analysis revealed mean CV in speed
      for the top-5 runners to be related to maximum ambient temperature (coefficient
      =.14, P < .05) and calendar year (coefficient = -.086, P = .034). CONCLUSIONS:
      Mountain trail running is characterized by wide variations in speed, but the
      fastest times are achieved when speed fluctuations are limited. This is generally
      accomplished by the winners remaining relatively close behind the lead runners
      before taking the lead in the middle half of the race, and then avoiding slowing
      as much as the other top runners in the latter race stages. Variations in speed
      increase with high ambient temperatures, and the small decrease in segmental
      speed variability among top runners across the nearly 30 y of this study suggests
      that the best runners have improved at pacing this race.

PMID- 24664981
TI  - Initial testing (stage 1) of the notch inhibitor PF-03084014, by the pediatric
      preclinical testing program.
AB  - PF-03084014, a gamma-secretase inhibitor, was tested against the PPTP in vitro
      cell line panel (1.0 nM to 10 MUM) and against the in vivo xenograft panels
      (administered orally twice daily on Days 1-7 and 15-21). PF-03084014 demonstrated
      limited in vitro activity, with no cell line achieving >=50% inhibition. PF
      03084014 induced significant differences in EFS distribution in 14 of 35 (40%)
      solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1
      mutation), but objective responses were not observed. PF-03084014 demonstrated
      limited single agent activity in vitro and in vivo against the pediatric
      preclinical models studied.

PMID- 24664983
TI  - A virus-based miRNA suppression (VbMS) system for miRNA loss-of-function analysis
      in plants.
AB  - MicroRNAs (miRNAs) play key roles in plant development and defense against
      pathogens. To establish the function of individual miRNAs, gain-of-function
      analysis is usually done by overexpressing a specific miRNA in transgenic plants
      and has proved very effective. Loss-of-function analysis by the target mimic
      method is now also increasingly being used. The mimics expressed in the
      transgenic plants sequester a specific miRNA and lead to changed phenotypes that
      elucidate miRNA function. However, it takes time to obtain the transgenic plants.
      To avoid using transgenic plants, we have developed a virus-based miRNA
      suppression system (VbMS) based on a Tobacco rattle virus vector. The target
      mimic sequences of miR156, miR319, or miR164 were introduced into the viral
      genomic RNA, which was then inoculated to Arabidopsis thaliana plants. The
      resulting phenotypes were consistent with previous reports from transgenic
      plants, and the expression of targets of the miRNAs was also increased showing
      that the activity of the miRNAs had been inhibited. VbMS developed here is
      validated for loss-of-function analysis of miRNA in plants. Moreover, since only
      simple agroinfiltration rather than transformation is needed, VbMS is suitable
      for large-scale approaches to miRNA function analysis in plants. 

PMID- 24664985
TI  - Free-flap telemonitoring to the surgeon's handheld device: proof of concept.

PMID- 24664984
TI  - Consulting a traditional healer and negative illness perceptions are associated
      with non-adherence to treatment in Indonesian women with breast cancer.
AB  - OBJECTIVE: The aim of the present study was to test the association between
      psychosocial factors and delay in uptake of treatment and treatment non-adherence
      in Indonesian women with breast cancer. METHODS: Seventy consecutive patients
      with breast cancer who were treated at the Hasan Sadikin Hospital in Indonesia
      were recruited. They completed a demographic form, the non-adherence
      questionnaire, the Breast Cancer Knowledge Test, the Brief Illness Perception
      Questionnaire, the Multidimensional Health Locus of Control Scales, the
      Satisfaction with Cancer Information Profile and the Distress Thermometer.
      RESULTS: Seventeen (24%) out of 70 patients reported that they had delayed
      initiating treatment at the hospital, and nine (13%) out of 70 patients had
      missed two or more consecutive treatment sessions. In the bivariate analyses, we
      found no significant differences on any of the psychological variables between
      patients who delayed initiating treatment and those patients who did not, whereas
      patients who had missed two or more consecutive sessions had lower satisfaction
      with the type and timing of information provided and more negative illness
      perceptions than patients who had not missed their sessions. In multivariate
      regression analyses, consulting a traditional healer before diagnosis was
      associated with treatment delay (beta = 1.27, p = 0.04). More negative illness
      perceptions (beta = 0.10, p = 0.02) and whether a traditional healer had been
      consulted after diagnosis (beta = 1.67, p = 0.03) were associated with missing
      treatment sessions. CONCLUSIONS: Indonesian health professionals need to be aware
      of patients' negative illness perceptions and their unrealistic belief in
      traditional healers.

PMID- 24664986
TI  - Autism characteristics and behavioural disturbances in ~ 500 children with Down's
      syndrome in England and Wales.
AB  - Recent research shows that a significant minority of children with Down's
      syndrome (DS) also meet diagnostic criteria for an autism spectrum disorder
      (ASD). The present study investigated what proportion of children aged 6-15 years
      with a confirmed diagnosis of DS in England and Wales display autistic-type
      behaviours, and explored the characteristics of this group of children. The
      Social Communication Questionnaire (SCQ) was used to screen for autism
      characteristics and the Strengths and Difficulties Questionnaire (SDQ) to explore
      behavioural difficulties. The proportion of children who met the cut-off score
      for ASD on the SCQ (total score >= 15) was 37.7% (95% CI: 33.4-42.0%); for autism
      (total score >= 22) the proportion was 16.5% (95% CI: 13.2-19.8%). Children who
      met the cut-off for ASD were significantly more likely to be reported as having
      emotional symptoms, conduct problems and hyperactivity on the SDQ than children
      who scored well below cut-off (total score < 10). However, the profile of their
      autism characteristics on the SCQ was atypical compared with individuals with
      idiopathic ASD. The pervasiveness of ASD in children with DS in England and Wales
      is substantially higher than in the general population. These children also
      experience significantly greater behavioural problems than children with DS only.
      Early detection of autism characteristics is important for appropriate
      intervention. However, the unusual profile of autism characteristics in this
      group may affect the recognition of the disorder and hinder the implementation of
      appropriate interventions.

PMID- 24664987
TI  - Laser assisted drug delivery: a review of an evolving technology.
AB  - BACKGROUND: Topically applied drugs have a relatively low cutaneous
      bioavailability. OBJECTIVE: This article reviews the existing applications of
      laser assisted drug delivery, a means by which the permeation of topically
      applied agents can be enhanced into the skin. RESULTS: The existing literature
      suggests that lasers are a safe and effective means of enhancing the delivery of
      topically applied agents through the skin. The types of lasers most commonly
      studied in regards to drug delivery are the carbon dioxide (CO2 ) and
      erbium:yttrium-aluminum-garnet (Er:YAG) lasers. Both conventional ablative and
      fractional ablative modalities have been utilized and are summarized herein.
      LIMITATIONS: The majority of the existing studies on laser assisted drug delivery
      have been performed on animal models and additional human studies are needed.
      CONCLUSIONS: Laser assisted drug delivery is an evolving technology with
      potentially broad clinical applications. Multiple studies demonstrate that laser
      pretreatment of the skin can increase the permeability and depth of penetration
      of topically applied drug molecules for both local cutaneous and systemic
      applications.

PMID- 24664988
TI  - Modeling of time dependent localized flow shear stress and its impact on cellular
      growth within additive manufactured titanium implants.
AB  - Bone augmentation implants are porous to allow cellular growth, bone formation
      and fixation. However, the design of the pores is currently based on simple
      empirical rules, such as minimum pore and interconnects sizes. We present a three
      dimensional (3D) transient model of cellular growth based on the Navier-Stokes
      equations that simulates the body fluid flow and stimulation of bone precursor
      cellular growth, attachment, and proliferation as a function of local flow shear
      stress. The model's effectiveness is demonstrated for two additive manufactured
      (AM) titanium scaffold architectures. The results demonstrate that there is a
      complex interaction of flow rate and strut architecture, resulting in partially
      randomized structures having a preferential impact on stimulating cell migration
      in 3D porous structures for higher flow rates. This novel result demonstrates the
      potential new insights that can be gained via the modeling tool developed, and
      how the model can be used to perform what-if simulations to design AM structures
      to specific functional requirements.

PMID- 24664990
TI  - Novel donor-acceptor polymer containing 4,7-bis(thiophen-2
      yl)benzo[c][1,2,5]thiadiazole for polymer solar cells with power conversion
      efficiency of 6.21%.
AB  - In order to improve the solution processability of 4,7-bis(thiophen-2
      yl)benzo[c][1,2,5]thiadiazole (DTBT)-based polymers, novel donor-acceptor polymer
      PTOBDTDTBT containing DTBT and benzo[1,2-b:4,5-b']dithiophene (BDT) with
      conjugated side chain is designed and synthesized with narrow band gap 1.67 eV
      and low lying HOMO energy level -5.4 eV. The blend film of PTOBDTDTBT and PC71 BM
      exhibits uniform and smooth film with root-mean-square (RMS) surface roughness
      1.15 nm because of the excellent solubility of PTOBDTDTBT when six octyloxy side
      chains are introduced. The hole mobility of the blend film is measured to be 4.4
      * 10(-5) cm(2) V(-1) s(-1) by the space-charge-limited current (SCLC) model. The
      optimized polymer solar cells (PSCs) based on PTOBDTDTBT/PC71 BM exhibits an
      improved PCE of 6.21% with Voc = 0.80 V, Jsc = 11.94 mA cm(-2) and FF = 65.10%,
      one of the highest PCE in DTBT containing polymers. 

PMID- 24664991
TI  - Relationships between driving distance, rheumatoid arthritis diagnosis, and
      disease-modifying antirheumatic drug receipt.
AB  - OBJECTIVE: Disease-modifying antirheumatic drugs (DMARDs) are recommended for all
      patients with rheumatoid arthritis (RA). Some estimate that approximately one
      half of patients with RA do not receive DMARDs. We hypothesized that patients
      with RA living farther from rheumatologists would be less likely to receive RA
      diagnoses and to receive DMARDs. METHODS: US-based Medicare patients ages >65
      years were study eligible. We calculated driving distance from patients' homes to
      the nearest rheumatologist. Using multivariable logistic regression, we assessed
      relationships between driving distance and RA diagnosis and between driving
      distance and DMARD receipt. In one set of analyses, distance was divided into
      quartiles: 0-2, 2.1-5, 5.1-15.9, and >=16 miles. In a second set of analyses, we
      used predefined categories: 0-15, 15.1-30, 30.1-60, and >60 miles. RESULTS: Among
      59,426 Medicare beneficiaries, 918 had diagnosed RA. Compared to the first
      quartile, increased distance was associated with decreased odds of RA diagnosis
      (odds ratio [OR] 0.96 [95% confidence interval (95% CI) 0.80-1.16] in second
      quartile, OR 0.88 [95% CI 0.72-1.07] in third quartile, and OR 0.72 [95% CI 0.56
      0.93] in fourth quartile; P < 0.01 for trend). Similar results were observed
      using predefined categories. Among those with RA, increased distance was
      associated with increased odds of DMARD receipt across quartiles (OR 1.15 [95% CI
      1.06-1.25] in second quartile, OR 1.41 [95% CI 1.29-1.54] in third quartile, and
      OR 1.32 [95% CI 1.18-1.46] in fourth quartile; P = 0.001 for trend). There was no
      relationship between predefined categories and DMARD receipt (P = 0.45 for
      trend). CONCLUSION: Increased driving distance to rheumatologists was associated
      with decreased odds of RA diagnosis. Among those with diagnosed RA, the odds of
      DMARD receipt rose as distance increased from <2 to 16 miles, but not beyond.
      Urban residents living closer to rheumatologists may have barriers to DMARD use
      besides geographic access.

PMID- 24664992
TI  - Ethnic variations in suicidal ideation and behaviors: a prominent subtype marked
      by nonpsychiatric factors among asian americans.
AB  - OBJECTIVE: Main objectives were to utilize multivariate rather than traditional
      regression approaches to capture the heterogeneity of subtypes of suicidal
      ideation and behaviors within ethnic minority groups. Mental illness is
      associated with suicidal ideation and behaviors in a vast majority of the general
      population, making psychopathology a common identifier of suicide risk. Yet
      recent studies suggest a need to better characterize suicidal ideation and
      behaviors among ethnic minorities and Asian Americans who do not exhibit the most
      commonly assessed risk factors. METHOD: The present study examined adults 18
      years of age or older from the National Latino and Asian American Study and
      utilized latent class analysis to classify 191 Asian Americans with a history of
      serious suicidal ideation or attempts from a community sample into subtypes.
      RESULTS: Two main subtypes resulted, including 48% in a "psychiatric" and 52% in
      a "nonpsychiatric" subtype of suicidal ideation and behaviors. The nonpsychiatric
      subtype was predominantly characterized by sociocultural factors (discrimination,
      family conflict, and low acculturation), medical problems, and limited
      functioning. The nonpsychiatric was less likely than the psychiatric subtype to
      seek help for mental health but was no different in access to a medical doctor,
      highlighting possible points of outreach. CONCLUSIONS: Findings advance the
      culture and suicide literature by highlighting how current research and practice
      that characterize suicidal ideation and behaviors as a mental health phenomenon
      may not comprehensively identify suicidality among an ethnic minority group.

PMID- 24664993
TI  - CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway.
AB  - CRKL is recently defined as a new oncogene, which plays a role in the lung cancer
      progression. However, the potential mechanism of CRKL in human non-small cell
      lung cancer cell invasion is obscure. We investigated the potential mechanism of
      CRKL in lung cancer cell invasion using immunohistochemistry, plasmid
      transfection, Western blotting, real-time PCR, matrigel invasion assay, chromatin
      immunoprecipitation assay, and luciferase reporter assay. CRKL expression is
      higher in lymph node metastatic tumor compared with primary tumor. CRKL
      overexpression enhanced cell invasion and MMP9 expression in both HBE and H1299
      cell lines. There was a significant correlation between CRKL overexpression and
      high MMP9 expression in primary tumors. MMP-9 antibody treatment significantly
      blocked cell invasion. CRKL overexpression also activated AP-1 luciferase
      reporter activity, ERK phosphorylation and association of c-fos to MMP9 promoter.
      Treatment with ERK inhibitor PD98059 in cells with CRKL transfection inhibited
      ERK activity, cell invasion, and MMP9 expression. These results suggested that
      overexpression of CRKL promoted cell invasion through upregulation of MMP9
      expression and activation of ERK pathway.

PMID- 24664994
TI  - Current status and trends in performance-based risk-sharing arrangements between
      healthcare payers and medical product manufacturers.
AB  - Our objective was to identify and characterize publicly available cases and
      related trends for performance-based risk-sharing arrangements (PBRSAs). We
      performed a review of PBRSAs over the past 20 years (1993-2013) using available
      databases and reports from colleagues and healthcare experts. These were
      categorized according to a previously published taxonomy of scheme types and
      assessed in terms of the underlying product and market attributes for each
      scheme. Macro-level trends were identified related to the timing of scheme
      adoption, countries involved, types of arrangements, and product and market
      factors. Our search yielded 148 arrangements. From this set, 65 arrangements
      included a coverage with an evidence development component, 20 included a
      conditional treatment continuation component, 54 included a performance-linked
      reimbursement component, and 42 included a financial utilization component. Each
      type of scheme addresses fundamental uncertainties that exist when products enter
      the market. The pace of adoption appears to be slowing, but new countries
      continue to implement PBRSAs. Over this 20-year period, there has been a
      consistent movement toward arrangements that minimize administrative burden. In
      conclusion, the pace of PBRSA adoption appears to be slowing but still has
      traction in many health systems. These remain a viable coverage and reimbursement
      mechanism for a wide range of medical products. The long-term viability and
      growth of these arrangements will rest in the ability of the parties to develop
      mutually beneficial arrangements that entail minimal administrative burden in
      their development and implementation.

PMID- 24664995
TI  - WatchBP Home A for opportunistically detecting atrial fibrillation during
      diagnosis and monitoring of hypertension: a NICE Medical Technology Guidance.
AB  - The Microlife((r)) 'WatchBP Home A' oscillometric blood pressure monitor detects
      irregular pulse, suggestive of atrial fibrillation (AF). Early detection of AF
      can prevent thromboembolic stroke via anticoagulation therapy. The device was
      considered by the Medical Technologies Evaluation Programme of the UK National
      Institute for Health and Care Excellence (NICE). The sponsor (Microlife)
      identified 10 studies. These were reviewed by an External Assessment Centre (EAC)
      which considered three relevant to the decision problem, including one which
      found the device detected AF more accurately (sensitivity 96.8%, specificity
      88.8%) than pulse palpation (87.2, 81.3%). The EAC concluded the technology had
      potential to improve detection of AF, but the three studies had uncertain
      external validity. From a cost-consequence model with a 1-year timeframe, the
      sponsor calculated the device would reduce electrocardiogram (ECG) referrals and
      prevent strokes, but incur anticoagulation therapy costs, with net NHS savings of
      L11.6 million and prevention of 221 strokes, annually. The EAC criticised the
      model for its limited time horizon, and its consideration of symptomatic AF
      patients who were outside the scope issued by NICE. The EAC applied a de novo
      Markov model, with a 10-year timeframe. The per use saving was calculated as
      L2.98 for asymptomatic patients aged 65-74 years and L4.26 for those aged 75-84
      years, with the prevention of 53-117 nonfatal and 28-65 fatal strokes per 100,000
      people screened. Following consideration by the NICE Medical Technologies
      Advisory Committee, NICE judged that the case for adoption was supported by the
      evidence (Medical Technologies Guidance 13; MTG13).

PMID- 24664996
TI  - Fabricating shaped microfibers with inertial microfluidics.

PMID- 24664997
TI  - [Dry powder inhalers in cystic fibrosis].
AB  - Inhaled medications play an important role in the daily treatment of patients
      with cystic fibrosis (CF). The classic route of administration was nebulisation
      via jet nebulisers. Respiratory delivery of fluid particles should loosen the
      viscid respiratory secretions, making airway clearance via cough or physiotherapy
      more efficient. Until recently, only jet nebulisers allowed to administer high
      doses of aerosolised antipseudomonal antibiotics. Powder inhalers for the
      treatment of cystic fibrosis have recently been made available. The newly
      developed powders and inhalers differ considerably from conventional dry powder
      inhalers used for the treatment of chronic obstructive airway disease. The
      present article will review two inhaled antibiotics, i. e. tobramycin and
      colistin, and the hyperosmotic agent mannitol, which increases the hydration of
      the airways. Topics are particle engineering, efficacy and tolerability results
      from clinical trials, as well as functional and practical aspects related to
      these new drugs. 

PMID- 24664999
TI  - Predictors of future health-related quality of life in survivors of adolescent
      cancer.
AB  - The purpose of this study was to identify characteristics associated with health
      related quality of life (HRQOL) among long-term survivors of adolescent cancer
      enrolled in the Childhood Cancer Survivor Study. Thirty percent of survivors
      reported poor physical and/or mental HRQOL. Race/ethnicity, education, and
      head/neck disfigurement were significantly associated with poor mental HRQOL,
      while sex, age, household income, obesity, alkylating agents, pelvic radiation,
      head/neck or limb disfigurement, and walking with a limp were associated with
      poor physical HRQOL. Identification of high-risk adolescent cancer patients may
      facilitate timely intervention to attempt to minimize the impact of cancer and
      treatment on subsequent quality of life.

PMID- 24665000
TI  - Facile identification of dual FLT3-Aurora A inhibitors: a computer-guided drug
      design approach.
AB  - Computer-guided drug design is a powerful tool for drug discovery. Herein we
      disclose the use of this approach for the discovery of dual FMS-like receptor
      tyrosine kinase-3 (FLT3)-Aurora A inhibitors against cancer. An Aurora hit
      compound was selected as a starting point, from which 288 virtual molecules were
      screened. Subsequently, some of these were synthesized and evaluated for their
      capacity to inhibit FLT3 and Aurora kinase A. To further enhance FLT3 inhibition,
      structure-activity relationship studies of the lead compound were conducted
      through a simplification strategy and bioisosteric replacement, followed by the
      use of computer-guided drug design to prioritize molecules bearing a variety of
      different terminal groups in terms of favorable binding energy. Selected
      compounds were then synthesized, and their bioactivity was evaluated. Of these,
      one novel inhibitor was found to exhibit excellent inhibition of FLT3 and Aurora
      kinase A and exert a dramatic antiproliferative effect on MOLM-13 and MV4-11
      cells, with an IC50 value of 7 nM. Accordingly, it is considered a highly
      promising candidate for further development.

PMID- 24665001
TI  - De novo heterozygous FBN1 mutations in the extreme C-terminal region cause
      progeroid fibrillinopathy.

PMID- 24665002
TI  - Long-term follow-up of changing practice patterns in breast reconstruction due to
      increased use of tissue expanders and perforator flaps.
AB  - BACKGROUND: As the science of breast reconstruction evolves, significant changes
      in reconstruction strategies and outcomes are expected. The purpose of this study
      is to determine the changes in breast reconstruction trends and outcomes that
      occurred at a multidisciplinary academic institution during the last decade.
      METHODS: We compared 265 patients over two distinct 6-month intervals separated
      by 5 years (2002 vs. 2007) and performed long-term follow-up (4.75 +/- 3.38 years
      2002, 2.99 +/- 2.25 years 2007). We studied patients seeking prophylactic
      mastectomy, patients with early breast cancer, and patients with locally advanced
      disease. We analyzed demographic data, breast cancer history and treatment, type
      and timing of reconstruction, and complications. RESULTS: Implant to flap
      reconstruction ratio was 48:49 in 2002 and 76:102 in 2007. Use of transverse
      rectus abdominis myocutaneous flap declined from 57 to 4%; conversely, deep
      inferior epigastric perforator flap increased from 27 to 91% (P < 0.001).
      Correspondingly, donor site chronic pain (4 vs. 0, P = 0.012) and postoperative
      abdominal wall bulge (9 vs. 3, P = 0.004) rates decreased. Timing of
      reconstruction showed increased staged cases in 2007 compared to 2002 (P =
      0.045). Post-final reconstruction radiation therapy was reduced in 2007 (P =
      0.016), with subsequent lower rates of implant rupture (P < 0.001). CONCLUSIONS:
      At our institution and over the last decade, increasing staged reconstructions
      have successfully reduced the rates of post-final reconstruction radiotherapy
      with optimized outcomes. Contrary to national trends, the rates of autologous
      flap reconstructions have increased with reduced donor site morbidity. This
      suggests that academic breast reconstruction trends are independent from national
      trends.

PMID- 24664998
TI  - Niemann-Pick C disease and mobilization of lysosomal cholesterol by cyclodextrin.
AB  - Niemann-Pick type C (NPC) disease is a lysosomal storage disease in which
      endocytosed cholesterol becomes sequestered in late endosomes/lysosomes (LEs/Ls)
      because of mutations in either the NPC1 or NPC2 gene. Mutations in either of
      these genes can lead to impaired functions of the NPC1 or NPC2 proteins and
      progressive neurodegeneration as well as liver and lung disease. NPC1 is a
      polytopic protein of the LE/L limiting membrane, whereas NPC2 is a soluble
      protein in the LE/L lumen. These two proteins act in tandem and promote the
      export of cholesterol from LEs/Ls. Consequently, a defect in either NPC1 or NPC2
      causes cholesterol accumulation in LEs/Ls. In this review, we summarize the
      molecular mechanisms leading to NPC disease, particularly in the CNS. Recent
      exciting data on the mechanism by which the cholesterol-sequestering agent
      cyclodextrin can bypass the functions of NPC1 and NPC2 in the LEs/Ls, and
      mobilize cholesterol from LEs/Ls, will be highlighted. Moreover, the possible use
      of cyclodextrin as a valuable therapeutic agent for treatment of NPC patients
      will be considered. 

PMID- 24665003
TI  - HILIC-UPLC-MS/MS combined with hierarchical clustering analysis to rapidly
      analyze and evaluate nucleobases and nucleosides in Ginkgo biloba leaves.
AB  - Ginkgo biloba leaf extract has been widely used in dietary supplements and more
      recently in some foods and beverages. In addition to the well-known flavonol
      glycosides and terpene lactones, G. biloba leaves are also rich in nucleobases
      and nucleosides. To determine the content of nucleobases and nucleosides in G.
      biloba leaves at trace levels, a reliable method has been established by using
      hydrophilic interaction ultra performance liquid chromatography coupled with
      triple-quadrupole tandem mass spectrometry (HILIC-UPLC-TQ-MS/MS) working in
      multiple reaction monitoring mode. Eleven nucleobases and nucleosides were
      simultaneously determined in seven min. The proposed method was fully validated
      in terms of linearity, sensitivity, and repeatability, as well as recovery.
      Furthermore, hierarchical clustering analysis (HCA) was performed to evaluate and
      classify the samples according to the contents of the eleven chemical
      constituents. The established approach could be helpful for evaluation of the
      potential values as dietary supplements and the quality control of G. biloba
      leaves, which might also be utilized for the investigation of other medicinal
      herbs containing nucleobases and nucleosides.

PMID- 24665004
TI  - Comparison of the risk of postoperative infection between transurethral
      vaporesection and transurethral resection of the prostate.
AB  - BACKGROUND AND OBJECTIVE: We observed in our department at 3 months two episodes
      of bacteremia postoperatively to photoselective vaporization of the prostate
      (PVP). We decided to compare the frequency of postoperative urinary tract
      infections (POUTIs) in patients with preoperative bacterial colonization of urine
      between PVP and transurethral resection of the prostate (TURP). MATERIALS AND
      METHODS: From January 2010 to December 2011, we studied patients who underwent
      PVP or TURP for benign prostatic obstruction in our department. Preoperative
      urine culture (UC) was carried out for all patients and we included those with
      preoperative bacterial colonization of the urinary tract. Patients were treated
      preoperatively with an appropriate antibiotic treatment and/or inductive
      prophylactic antibiotics. Patients were diagnosed with POUTI if they had clinical
      signs of infections (e.g., fever) and a positive UC during the month after
      surgery. RESULTS: Patients were treated by PVP in 49 cases and TURP in 62 cases.
      A preoperative indwelling urinary catheter was inserted in 80% of the patients.
      During the postoperative period, eight episodes of fever were identified in the
      PVP group (16%), five (8%) in the TURP group (P = 0.18). We then studied the
      subgroup of patients with multiple bacteria strains present in the preoperative
      UC and identified significant differences. The risk of POUTI was significantly
      higher in patients treated by PVP than in those treated by TURP (P = 0.018).
      CONCLUSIONS: We found significant differences between subgroups of patients with
      positive preoperative cultures (containing various bacterial strains). The risk
      of POUTI was significantly higher in patients treated by PVP.

PMID- 24665006
TI  - A tortuous proximal urethra in urorectal septum malformation sequence?
AB  - We observed a newborn boy with urorectal septum malformation sequence. Anomalies
      of the genitalia and rectum were present. He expired on the first day of life,
      due to severe lung hypoplasia. Autopsy showed a colon that ended in a blind sac,
      an enlarged bladder with no grossly visible urethra, and dysplastic kidneys. A
      cone-shaped tissue at the usual site of the bladder outlet contained tortuous and
      slit-like lumina, suggesting an undeveloped proximal urethra. The urethral
      structure was lined by transitional epithelium with squamous metaplasia. Many
      small buds-lined with columnar epithelium-branched from the urethral structure.
      These ductal buds lined with columnar epithelium stained for prostatic acid
      phosphatase. Basal cells surrounding the ductal buds stained for p63 and high
      molecular weight cytokeratin-supporting an interpretation that the buds were
      early prostatic ducts with normal histology. To our knowledge, these are the
      first histological images of an undeveloped, obstructed urethra associated with
      the urorectal septum malformation sequence.

PMID- 24665007
TI  - Commentary: educational technology for the next five years: the NMC horizon
      report.

PMID- 24665005
TI  - Cadherin 5 is regulated by corticosteroids and associated with central serous
      chorioretinopathy.
AB  - Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from
      the choroid into the subretinal space and, consequently, loss of central vision.
      The disease is triggered by endogenous and exogenous corticosteroid imbalance and
      psychosocial stress and is much more prevalent in men. We studied the association
      of genetic variation in 44 genes from stress response and corticosteroid
      metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC
      cases and 1,400 matched controls. The expression of cadherin 5 (CDH5), the major
      cell-cell adhesion molecule in vascular endothelium, was downregulated by
      corticosteroids which may increase permeability of choroidal vasculature, leading
      to fluid leakage under the retina. We found a significant association of four
      common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic
      variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant
      associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P
      = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively. A common haplotype was
      present in 25.4% male CSC cases and in 35.8% controls (P = 0.0002; OR = 0.61, 95%
      CI [0.47-0.79]). We propose that genetically predetermined variation in CDH5,
      when combined with triggering events such as corticosteroid treatment or severe
      hormonal imbalance, underlie a substantial proportion of CSC in the male
      population.

PMID- 24665008
TI  - The effect of twisting on single and double based perforator flap viability: an
      experimental study in rats.
AB  - In this study, the histological and vital effects of rotation on multiple and
      single based perforator flaps were evaluated. A 6 cm * 6 cm abdominal perforator
      flap model was used on 80 male rats; half of these received a single-pedicled
      flap, and the other half double-pedicled. The flaps of control subgroups were
      raised and sutured without rotation. In rotation subgroups 90-, 180-, 270-degree
      rotations were performed, and rotation effects on flap viability and histological
      changes were analyzed. Among single- and double-pedicled perforator flaps,
      respectively, mean survival area was 12.59 cm(2) and 27.84 cm(2) in non-rotated
      subgroups, 12.49 cm(2) and 17.06 cm(2) in 90-degree rotation subgroups, 5.96
      cm(2) and 9.96 cm(2) in 180-degree rotation subgroups, and 1.45 cm(2) and 1.70
      cm(2) in 270-degree rotation subgroups. While survival areas of double- and
      single-pedicled perforator flaps with the same rotation degree showed no
      statistically significant difference, non-rotated double-pedicled perforator
      flaps had a statistically larger survival area compared to single-pedicled
      perforator flap (P = 0.001). In the single-pedicled flap group, there were no
      statistical differences between survival flap areas of the non-rotated subgroup
      and the 90- and 180-degree rotation subgroups (P > 0.05), but the non-rotated
      subgroup had a statistically larger survival area compared to the 270-degree
      rotation subgroup (P = 0.003). In double-pedicled perforator flap group, the
      control subgroup had a statistically larger flap survival area compared to 90
      degree, 180-degree, and 270-degree rotation subgroups (P = 0.004, P = 0.002, P =
      0.001). Degenerative histological changes gradually increased in correlation with
      the rotation angle in both single- and double-pedicled groups. When double- and
      single-pedicled groups were compared; degenerative histology score displayed no
      statistical difference between control subgroups and rotated subgroups (P >
      0.05). In this rat abdominal propeller perforator flap model, we found that
      double perforators without pedicle rotation could support larger flap survival
      when compared to the single pedicle. However, double perforators did not cause an
      increase of survival area when pedicles were rotated. In the single-pedicled
      perforator flap, the flap survival area did not significantly decrease until 180
      degree pedicle rotation. In the double-pedicled perforator flap, the flap
      survival area decreased when the degree of rotation increased. The degenerative
      changes increased in correlation with the rotation degree in both single- and
      double-pedicled perforator flaps.

PMID- 24665009
TI  - Functional core/shell drug nanoparticles for highly effective synergistic cancer
      therapy.
AB  - Gold (Au)-nanoshelled 10-hydroxycamptothecin nanoparticles (HCPT NPs) are
      developed with combination of photothermal therapy and chemotherapy for highly
      effective cancer therapy. The strong near-infrared (NIR) absorbance from Au
      nanoshells endows the nanocomposites photothermal effects and on-demand drug
      release. Notably, the drug-loading content reaches up to 63.7 wt%, which is much
      higher than that in the previously reported nanovehicles systems. Both in vitro
      and in vivo studies indicate that the combined local specific chemotherapy with
      external NIR photothermal therapy demonstrates a synergistic effect, which is
      significantly better than either of them alone. More importantly, due to the high
      drug-loading content and efficient photothermal effects of the nanocomposites,
      100% in vivo tumor elimination is achieved at a low laser irradiation power
      density of 1 W cm(-) (2) without weight loss and tumor recurrence. No obvious
      systematic toxicity is observed for the injected mice, indicating the good
      biocompatibility of this kind of multifunctional drug nanocomposites. This work
      highlights the great potential of drug-nanostructure-based multifunctional
      core/shell nanpocomposite for highly efficient cancer therapy. 

PMID- 24665011
TI  - [Triathlon sport -- doping und brain doping--hand in hand?].

PMID- 24665012
TI  - [Adaptive mechanisms and behavioural recommendations: playing football in heat,
      cold and high altitude conditions].
AB  - Football is played worldwide and players often have to cope with hot and cold
      temperatures as well as high altitude conditions. The upcoming and past world
      championships in Brazil, Qatar and South Africa illustrate the necessity for
      behavioural strategies and adaptation to extreme environmental conditions. When
      playing football in the heat or cold, special clothing, hydration and nutritional
      and acclimatisation strategies are vital for high-level performance. When playing
      at high altitude, the reduced oxygen partial pressure impairs endurance
      performance and alters the technical and tactical requirements. Special high
      altitude adaptation and preparation strategies are essential for football teams
      based at sea-level in order to perform well and compete successfully. Therefore,
      the aim of the underlying review is: 1) to highlight the difficulties and needs
      of football teams competing in extreme environmental conditions, 2) to summarise
      the thermoregulatory, physiological, neuronal and psychological mechanism, and 3)
      to provide recommendations for coping with extreme environmental conditions in
      order to perform at a high level when playing football in the heat, cold and at
      high altitude. 

PMID- 24665010
TI  - Epigenetic analysis of microRNA genes in tumors from surgically resected lung
      cancer patients and association with survival.
AB  - Aberrant microRNA (miRNA) expression is involved in tumorigenesis of several
      cancers, including non-small cell lung cancer (NSCLC). Furthermore, expression of
      some miRNAs has been shown to be under epigenetic regulation. However, less is
      known regarding the role of miRNA methylation in NSCLC development or clinical
      outcomes. Therefore, we tested miRNA methylation patterns by quantitative real
      time methylation-specific PCR for a panel of candidate miRNAs in 19 NSCLC paired
      tumor and adjacent normal tissues. For assessment of survival, methylation was
      measured in a total of 97 tumor tissues with complete clinical and follow-up
      data. Analysis was also performed for correlation with age at diagnosis, gender,
      smoking, and stage. Significant differences in methylation patterns were observed
      for 9 of the 12 miRNAs, all due to hypermethylation in the tumor tissue.
      Individuals with the highest levels of methylated miR-127 were at a significantly
      increased risk of dying with a hazard ratio of 1.93 (95% CI 1.17-3.19; P =
      0.010), in univariate analysis and remained significant after adjusting for age,
      gender, and stage (HR 1.97; 95% CI 1.15-3.40; P = 0.014). This increase in risk
      due to increased methylation were accompanied by significant, dramatic difference
      in survival duration of 17 months (P = 0.0089). Six of the 12 miRNAs were
      significantly positively correlated with age at diagnosis. Additionally,
      methylation of miR-127 was significantly greater in higher stage tumors compared
      to lower stage tumors (P = 0.0039). However, no significant associations between
      smoking and gender with miRNA methylation were observed. Our results demonstrate
      that miRNA methylation plays a role in NSCLC tumorigenesis and prognosis.

PMID- 24665013
TI  - [Tibial plateau fractures in alpine skiing--return to the slopes or career end?].
AB  - BACKGROUND: Fractures of the tibial plateau are among the most severe injuries of
      the knee joint and are often the result of sports accidents, especially skiing
      accidents. PATIENTS/MATERIALS AND METHODS: Between January 2003 and March 2009, a
      total of 37 skiers with tibial plateau fractures were treated operatively at
      Klinikum rechts der Isar, Munich (level I trauma center); 28 patients with a
      minimum follow-up of 24 months were included in this study. Sporting activity was
      determined at the time of injury and at the time of survey at an average follow
      up of 49.0 months postoperatively. RESULTS: At the time of the survey, 92.9% of
      all patients were engaged in sports; only 12 of the 28 patients returned to
      skiing. Of the competitive athletes (n = 5 at time of injury) no patient returned
      to competition. The number of different sporting activities declined
      significantly from 6.4 before the injury to 4.6 after the injury. The activity
      duration per week, being 5.0 hours at the time of injury, declined to 4.4 hours,
      although the difference is statistically not significant. The Lysholm score, 97.5
      points before accident, illustrated a significant decline to 84.4 points.
      Activity levels according to the Tegner scale declined significantly from 6.1 to
      4.7 after the tibial plateau fracture. CONCLUSION: The majority of patients could
      not return to their previous level of activity. For patients playing competitive
      sports, the tibial plateau fracture can be a career ender. Overall, 92.9% of the
      patients returned to sports, but we noticed a post-injury shift toward activities
      with less impact. Only 12 of the 28 (42.9%) skiers with tibial plateau fractures
      returned to skiing.

PMID- 24665014
TI  - [Balance trainability using the Nintendo Wii balance board in sportive people].
AB  - BACKGROUND: A multivariable training has a positive impact on balance skills and
      risk of injury. To date the effect of this training using the Nintendo Wii
      balance board in sportive people has not yet been investigated. OBJECTIVE: The
      aim of this study was to investigate whether training with the Nintendo Wii
      balance board can improve balance skills. METHOD: 20 people were randomized into
      a control and an intervention group each with 10 people who performed a
      unilateral stance test with eyes open and closed as well as the star excursion
      balance test before and after the intervention. The control group completed their
      usual sports and the intervention group an adjunct training with the Nintendo Wii
      balance board for 4 weeks. RESULTS: Adjunct Training using the Nintendo Wii
      Balance Board did not improve sportive people's balance skills significantly. The
      intervention group, however, attained better results in the star excursion
      balance test, whereas the control group did not show any changes. The unilateral
      stance tests did not provide significant differences before and after training
      within both groups. CONCLUSION: The use of the Nintendo Wii balance board should
      be further investigated by employing individual difficulty levels.

PMID- 24665015
TI  - [Dear readers].

PMID- 24665016
TI  - Collecting women's reproductive histories.
AB  - The importance of women's reproductive histories for scientific questions
      mandates rigor in collecting data. Unfortunately, few studies say much about how
      histories were constructed and validated. The aim of this report, therefore, is
      to illustrate the elements of a rigorous system of data collection. It focuses
      particularly on potential sources of inaccuracy in collecting reproductive
      histories and on options for avoiding them and evaluating the results. A few
      studies are exemplary in their description of methods of data collection and
      evaluation of data quality because they clearly address the main issues of
      ascertaining whether or not an event occurred and, if so, its timing. Fundamental
      variables such as chronological age, live birth, or marriage may have different
      meanings in different cultures or communities. Techniques start with asking the
      appropriate people meaningful questions that they can and will answer, in
      suitable settings, about themselves and others. Good community relations and well
      trained, aware interviewers who check and cross-check, are fundamental. A range
      of techniques estimate age, date events, and optimize the value of imperfect
      data. Robust data collection procedures rely on skillful and knowledgeable
      interviewing. Reliability can be improved, evaluated and explained. Researchers
      can plan to implement robust data collection procedures and should assess their
      data for the scientific community to raise confidence in reproductive history
      data.

PMID- 24665017
TI  - Facile cell sheet manipulation and transplantation by using in situ gelation
      method.
AB  - Cell sheets harvested from temperature-responsive cell culture dishes (TRDs) has
      attracted considerable attention as effective tools for reconstructing the lost
      functions of tissues and organs in the regenerative medicine field. However,
      because of their thinness, handling problems sometimes arise when transferring
      cell sheets from a TRD to a target surface. In this study, we developed a facile
      cell transfer method referred to as in situ gelation by using both gelatin
      hydrogel and a support membrane. Gelation and low-temperature processes were
      simultaneously performed on TRD. Confluent cultured cells were efficiently
      harvested from TRD in less than 5 min by decreasing the incubation temperature to
      20 degrees C. Harvested cells were found to maintain their cell viability,
      extracellular matrix, and original shape, thus allowing transfer of the cells to
      another surface with a short incubation time at 37 degrees C. This method is
      applicable for various cell types regardless of the formation of tight cell-cell
      junctions. In addition, because of the high flexibility of the gelatin-coated
      membrane, cells were efficiently transferred to the surface of a mouse subcutis
      and liver. When compared with conventional cell sheet manipulation methods, the
      interaction between the cell surface and membrane was reinforced by the uniformly
      formed gelatin gel layer without using a special device. Therefore, the in situ
      gelation method is a promising technique for cell sheet-based tissue engineering
      and regenerative medicine.

PMID- 24665019
TI  - What's the deal? Trends in Irish street-level heroin and cocaine 2010-2012.

PMID- 24665020
TI  - Electrically conductive ultrananocrystalline diamond-coated natural graphite
      copper anode for new long life lithium-ion battery.

PMID- 24665021
TI  - 'A la carte' peptide shuttles: tools to increase their passage across the blood
      brain barrier.
AB  - Noninvasive methods for efficient drug delivery to the brain is an unmet need.
      Molecular access to the brain is regulated by the blood-brain barrier (BBB)
      established by the endothelial cells of brain vessels. Passive diffusion is one
      of the main mechanisms that organic compounds use to travel through these
      endothelial cells. This passage across the BBB is determined mainly by certain
      physicochemical properties of the molecule such as lipophilicity, size, and the
      presence of hydrogen bond donors and acceptors. One emerging strategy to
      facilitate the passage of organic compounds across the BBB is the use of peptide
      shuttles.1 In using this approach the permeability in front the BBB is, clearly,
      determined by the combined physicochemical properties of both the cargo and the
      shuttle. Herein we report the synthesis of a series of variations of one of the
      more efficient peptide shuttles, (N-MePhe)n . These include diverse structural
      features such as various backbone stereochemistries or the presence of non
      natural amino acids, including halogenated residues. In several cases, we
      assessed the BBB permeability of both the shuttles alone and linked to a few
      cargos. Our results show how factors such as stereochemistry or halogen content
      influences the passage across the BBB and, more importantly, opens the way to a
      strategy of peptide shuttles 'a la carte', in which a particular fine-tuned
      shuttle is used for each specific cargo. 

PMID- 24665018
TI  - Developmental remodeling of corticocortical feedback circuits in ferret visual
      cortex.
AB  - Visual cortical areas in the mammalian brain are linked through a system of
      interareal feedforward and feedback connections, which presumably underlie
      different visual functions. We characterized the refinement of feedback
      projections to primary visual cortex (V1) from multiple sources in juvenile
      ferrets ranging in age from 4-10 weeks postnatal. We studied whether the
      refinement of different aspects of feedback circuitry from multiple visual
      cortical areas proceeds at a similar rate in all areas. We injected the neuronal
      tracer cholera toxin B (CTb) into V1 and mapped the areal and laminar
      distribution of retrogradely labeled cells in extrastriate cortex. Around the
      time of eye opening at 4 weeks postnatal, the retinotopic arrangement of feedback
      appears essentially adult-like; however, suprasylvian cortex supplies the
      greatest proportion of feedback, whereas area 18 supplies the greatest proportion
      in the adult. The density of feedback cells and the ratio of
      supragranular/infragranular feedback contribution declined in this period at a
      similar rate in all cortical areas. We also found significant feedback to V1 from
      layer IV of all extrastriate areas. The regularity of cell spacing, the
      proportion of feedback arising from layer IV, and the tangential extent of
      feedback in each area all remained essentially unchanged during this period,
      except for the infragranular feedback source in area 18, which expanded. Thus,
      while much of the basic pattern of cortical feedback to V1 is present before eye
      opening, there is major synchronous reorganization after eye opening, suggesting
      a crucial role for visual experience in this remodeling process.

PMID- 24665022
TI  - Congenital cytomegalovirus infection and small for gestational age infants.
AB  - OBJECTIVE: To evaluate the incidence of infants with birth weight less than the
      10(th) centile for small for gestational age (SGA) in primary maternal
      cytomegalovirus (CMV) infection and to determine whether SGA predicts poor
      neurodevelopmental outcome. METHODS: A retrospective cohort study, which included
      singleton live-born infants from pregnancies complicated by primary maternal CMV
      infection. Infants were classified as uninfected or infected based on viral virus
      isolation and real-time PCR in urine at birth. SGA neonates rate and long-term
      sequelae were evaluated. RESULTS: Between 2000 and 2012, 848 women with primary
      CMV infection were referred to our center with 588 infants assessed at birth.
      Congenital CMV infection was diagnosed in 119 cases (20%), of which 8 were SGA
      (6.7%) compared with 27 out of the 469 uninfected infants (5.7%) (p-value =
      0.69). Among the 119 infected babies, 14 infants were symptomatic at birth or at
      postnatal follow-up (12%), of whom two were SGA compared with six out of the 105
      asymptomatic neonates (5.7% versus 15%, respectively, p-value = 0.22).
      CONCLUSION: Congenital CMV infection does not seem to be associated with a higher
      incidence of SGA, and long-term outcomes do not seem to be affected by isolated
      impaired fetal growth.

PMID- 24665023
TI  - TP53 mutations in human cancer: database reassessment and prospects for the next
      decade.
AB  - More than 50% of human tumors carry TP53 gene mutations and in consequence more
      than 45,000 somatic and germline mutations have been gathered in the UMD TP53
      database (http://p53.fr). Analyses of these mutations have been invaluable for
      bettering our knowledge on the structure-function relationships within the TP53
      protein and the high degree of heterogeneity of the various TP53 mutants in human
      cancer. In this review, we discuss how with the release of the sequences of
      thousands of tumor genomes issued from high-throughput sequencing, the
      description of novel TP53 mutants is now reaching a plateau indicating that we
      are close to the full set of mutants that target the elusive tumor-suppressive
      activity of this protein. We performed an extensive and thorough analysis of the
      TP53 mutation database, focusing particularly on specific sets of mutations that
      were overlooked in the past because of their low frequencies, for example,
      synonymous mutations, splice mutations, or mutations-targeting residues subject
      to posttranslational modifications. We also discuss the evolution of the
      statistical methods used to differentiate TP53 passenger mutations and
      artifactual data from true mutations, a process vital to the release of an
      accurate TP53 mutation database that will in turn be an invaluable tool for both
      clinicians and researchers. 

PMID- 24665024
TI  - Detectability of new psychoactive substances, 'legal highs', in CEDIA, EMIT, and
      KIMS immunochemical screening assays for drugs of abuse.
AB  - The increasing number of new psychoactive substances made available for
      recreational drug use has created a challenge for clinical toxicology and drug
      testing laboratories. As a consequence, the routine immunoassay drug testing may
      become less effective due to an increased occurrence of false negative and false
      positive screening results. This work aimed to extend the knowledge about
      analytical cross-reactivity of new substances in selected CEDIA, EMIT, and KIMS
      immunoassays for drugs-of-abuse screening. Urine standards were prepared by
      spiking blank urine with 45 new substances. Authentic urine samples from
      intoxication cases identified by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) were also studied. Several new psychoactive substances were
      demonstrated to display cross-reactivity in the immunoassays. CEDIA
      Amphetamine/Ecstasy and EMIT d.a.u. Amphetamine Class tests showed the highest
      reactivity towards the new drugs, which was expected since many have amphetamine
      like structure and activity. In the samples from authentic cases, five new
      substances displayed 100% detection rate in the CEDIA Amphetamine/Ecstasy test.
      In conclusion, cross-reactivity data in routine urine drug screening immunoassays
      for a number of new psychoactive substances not studied before were reported. In
      both spiked and authentic urine samples, some new substances showed significant
      cross-reactivity and are thus detectable in the routine screening methods.

PMID- 24665025
TI  - [Salvage laparoscopic pyeloplasty in the worst case scenario: after failed open
      repair and endoscopic salvage].
AB  - OBJECTIVES: We present the video of a laparoscopic correction of a left
      ureteropelvic junction obstruction in a patient who has already undergone
      previous surgical open pyeloplasty and subsequent acucise for failure of the
      first surgery. At 8 years after the second surgery, the patient showed a
      recurrence of the obstruction of the left ureteropelvic junction.? It was decided
      to perform the retroperitoneal laparoscopic correction of the obstruction.?
      MATERIALS AND METHODS: With the patient placed in a 90 degrees  flank position, 4
      trocars are placed in the retroperitoneum space by the Hasson tecnique.? After
      the creation of the retroperitoneum space, the Gerota's fascia is opened. The
      posterior layer of the Gerota's fascia appears very thickened at the level of the
      lower pole of the kidney and is very adherent with the surrounding structures, in
      particular the psoas muscle.? Gerota's fascia is incised and removed from the
      previous surgery and the psoas muscle is identified. The distal lumbar ureter is
      tenaciously anchored to the psoas muscle. The lower pole of the kidney is freed
      from the adhesions of the previous surgery. The proximal ureter is hardly
      isolable for the presence of fibrosis. The renal pelvis is fixed to the psoas due
      to fibrotic tissue that is cut with scissors. Once the pelvis and the ureter are
      separated from the psoas, the surgery proceeds with the liberation of the pelvis
      from the adipose tissue and fibrosis that surround it. The pieloureteral
      obstruction is not easily identifiable. The renal pelvis is opened at the level
      of the ureteral junction, the ureter is spatulated on its medial side. The scar
      tissue is removed until well vascularized tissue is seen. The anastomosis between
      the ureter and pelvis is performed with 2 semicontinuous running sutures. Once
      the anterior plate of the anastomosis is completed a cystoscopic retrograde DJ
      ureteral stent insertion is performed. The procedure ends with the packaging of
      the posterior plate of the anastomosis with the second running suture.? RESULTS:
      The operation lasted 180 minutes. The postoperative course was uneventful, the
      drain was removed on the second day and the bladder catheter on the 4th. The
      patient was discharged on the 5th day and the DJ ureteral stent was removed on
      the 21st post-operative day. ? DISCUSSION: The laparoscopic reoperation in
      patients with previous open surgery interventions is definitely difficult. This
      kind of surgery has to be carried out after having gained considerable
      laparoscopy experience. Specifically, the reoperation of laparoscopic pyeloplasty
      after 2 previous intervention poses the following difficulties: the creation of
      appropriate space, dissection of the ureter and pelvis from the psoas muscle,
      appropriate mobilization of the lower pole of the kidney to get a "tension free"
      anastomosis, liberation of the pelvis and ureter from the tenaciously adherent
      fibrotic tissue, identification of the stenotic ureteropelvic junction.?
      CONCLUSIONS: Laparoscopic pyeloplasty after failure of past interventions remains
      a difficult procedure that should only be performed after major laparoscopic
      experience. In experienced hands, redo laparoscopic pyeloplasty provides high
      success rates.

PMID- 24665026
TI  - [Urethral injuries secondary to implantation of penile prosthesis. Analysis of
      the causes, prevention and treatment].
AB  - Urethral injuries due to penile prosthesis implant represent a rare complication
      of the intervention to position penile prosthesis, but unfortunately scientific
      literature about this is poor. This rare complication may occur during surgery
      and in the postoperative period, both early and late. It recognizes a variety of
      causes that may include anatomical or functional conditions, for example
      cavernosal fibrosis or outcomes of inflammations or previous urethral lesions and
      pathological sensibility due to diabetic neuropathy or other forms of neuropathy
      including those from spinal cord injury or myelopathy. This review evaluates the
      possible predisposing conditions, the clinical presentations, and the devices in
      the surgical procedures to use to minimize the risk of onset of this lesions and
      the measures to take if they occur. 

PMID- 24665027
TI  - [Sperm collection for medically assisted procreation in azoospermic patients].
AB  - Infertility is defined as the inability of a sexually active non-contracepting
      couple to achieve spontaneous pregnancy in one year.? Factors of male infertility
      are present in 50% of infertile couples.? Azoospermia is defined as the absence
      of sperm in the ejaculate, even after centrifugation of the sample, and affects
      10%-15% of the infertile male population. Therefore, it represents a pathological
      condition of primary importance in the context of infertility management.? Any
      assisted reproductive procedure must first refer to the availability of a
      suitable number of good quality gametes.? As regards sperm collection, if
      ejaculated semen is not suitable or available, it may be taken from the seminal
      duct or directly from the testicular parenchyma with different methodologies and
      techniques, which can be divided into percutaneous techniques and open surgical
      (TeSE and ESA) or micro-surgical (micro-TeSE) techniques.? The purpose of this
      work is to evaluate and compare the retrieval rate in infertile patients
      suffering from azoospermia and treated with the various surgical techniques.

PMID- 24665028
TI  - [Incidence and distribution of lymphoid neoplasm of the urinary tract and male
      genital organs in an urban area of northern Italy in the last decade].
AB  - INTRODUCTION: Lymphoid neoplasms of the urinary tract and male genital organs are
      relatively rare, comprising less than 5% of all primary extranodal lymphomas;
      only a handful of small case series and isolated case reports have been published
      to describe their predominant sites and subtypes.? MATERIALS AND METHODS: We
      searched our institution's electronic archive of pathology reports from ?2001 to
      2012. We considered lymphoid neoplasms involving the kidney, bladder, testes and
      prostate. Patient age at diagnosis, sex, clinical history, and outcome were
      recorded using the relevant electronic medical records.? RESULTS: We identified
      25 patients with lymphoid neoplasms of the urogenital tract. 11 cases out of 40
      were primary genitourinary lymphomas. Mean age at diagnosis was 61.7 years (range
      13-87 years). Among bladder lymphomas cases, a male predominance was noted. As
      regards the types of lymphoid neoplasms, the following subtypes were observed:
      diffuse large B-cell lymphoma (32%), chronic lymphocytic leukemia (24%), small
      lymphocytic lymphoma (20%), Malt lymphoma (8%), Burkitt lymphoma (4%), follicular
      lymphoma (4%); diffuse large B-cell ALK+ (4%) and lymphoblastic lymphoma (4%).?
      RESULTS: Genitourinary tract lymphomas most commonly occurred in the kidney. B
      cell non-Hodgkin's lymphomas were predominant, with diffuse large B-cell lymphoma
      being the most common subtype in the entire group. Although this study confirms
      the predominance of diffuse large B-cell lymphoma in extranodal sites, the
      findings also highlight the variety of lymphomas that may occur in the
      genitourinary tract. This diversity of subtypes affirms the importance of fully
      characterizing lymphomas by immunohistochemistry and other modalities, which are
      indispensable for accurate diagnosis.

PMID- 24665029
TI  - [?Robotic pyeloplasty: the results after the first 30 patients].
AB  - INTRODUCTION: The aim of this paper is to report the outcomes of 30 (first) robot
      assisted pyeloplasties (RPs) performed at our institute for the treatment of
      ureteropelvic junction obstruction (UPJO).? METHODS: In the period between March
      2005 and September 2012, 30 RPs due to UPJO have been performed at our institute
      using a three arms Da Vinci Robot, standard version. All the procedures were
      performed transperitoneally with Anderson-Hynes technique. 29/30 (97%) patients
      were affected by primary UPJO and 1/30 (3%) reported a recurrent disease. The
      access foresaw the positioning of three robotic trocars (one 12 mm trocar for the
      camera and two 8-mm trocars for the robotic arms) and one assistant 12 mm trocar.
      The anastomosis was confectioned on a double-J ureteral tutor with 4/0 monocryl
      running sutures. Outcome success was defined as resolution of preoperative
      symptoms and ureteropelvic junction obstruction, confirmed by the improvement of
      the diuretic renogram. Mean follow-up was 48.3 months (range 5-96).? RESULTS: All
      procedures have been completed robotically and no conversion was needed. ?Mean
      operative times, blood losses and hospital stay were respectively 189 minutes
      (range 105-420), 60 mL (range 25-100) and 4.2 days (range 2-14).? 29/30 patients
      were cured, with a success rate of 97%.? As regards mild complications, 3/30
      patients (10%) reported a moderate abdominal pain a few hours after surgery,
      which was successfully treated with common analgesic drugs.? A s for major
      complications, one patient (3%) developed ileus, probably due to a mild urine
      extravasation through the ureteropelvic suture, which spontaneously disappeared
      three days after surgery.? CONCLUSION: RP seems to be a "new gold standard" in
      the treatment of UPJO.? The three-dimensional versatility and the outstanding
      accuracy of robot-assisted intracorporeal suturing produced excellent results
      after the first procedures without requiring a previous 'sound' laparoscopic
      experience.

PMID- 24665030
TI  - [Prostate brachytherapy: oncological and functional results after 400 cases].
AB  - INTRODUCTION: Brachytherapy (BT) with real-time technique for the treatment of
      low and medium risk prostate cancer (CaP) has been a well known practice for over
      25 years in the USA and for over ?15 years in Italy. However, it is an uncommon
      procedure, because of problems related to the organization and cooperation among
      urologists, radiotherapists and physics, to the competition of alternative
      therapies, to dogmatic and educational beliefs, and to the poor knowledge of this
      technique.? METHODS: Between May1999 and July 2013, 400 patients with low and
      medium risk CaP underwent I 125 BT using a "real-time" approach. The seeds
      implantation was performed using a Mick applicator in the first 190 patients and
      the "QuickLink" technique in the last 210 cases. Oncologic results were reported
      for the first 250 cases with a mean follow-up of 10 years, while functional
      outcomes and complications were assessed in 350 patients with a minimum follow-up
      of 1 year.? RESULTS: A good quality implantation was assessed in 90% of the
      patients (D90>145 Gy). A biochemical failure was assessed, based on Phoenix
      criteria, in 12 patients (4.8%). Out of these patients, ?10 underwent prostate
      biopsy (the other 2 patients showed a systemic disease). The biopsy showed a CaP
      in 6/10 patients who underwent retropubic radical prostatectomy (4 patients) and
      external radiotherapy (2 patients) respectively. The remaining 4/10 patients with
      negative biopsy were treated with total androgen blockade (3 patients) and
      watchful waiting (1 patient) respectively. Functional results showed an incidence
      of postoperative irritative disorders in 70% of the patients during the first six
      months and a good recovery of erectile function in 78.8% and 68.2% of the
      patients after one and five years from BT respectively.? CONCLUSION:
      Brachytherapy is a good alternative to radical prostatectomy in the low and
      medium risk prostatic cancers with excellent oncologic and functional results.

PMID- 24665031
TI  - [Ejaculatory system cysts: a case report].
AB  - INTRODUCTION: Male pelvic floor cysts are a rare clinical entity that include:
      Wolffian duct remnants, Mullerian duct remnants, cysts of the seminal vesicles,
      prostate and ejaculatory duct/vas deferens cysts.? CASE REPORT: We report the
      clinical case of a 21-year-old male patient with a history of previous surgery in
      childhood and more precisely: partial colectomy for congenital megacolon, removal
      of dysplastic right kidney and subsequent surgical adhesiolysis for bowel
      obstruction.? At 17, the patient was submitted to MRI for groin pain with an
      incidental finding of a cystic mass at the level of the right seminal vesicle.
      Consequently, a TUR-ED was performed at another urology unit, for a suspected
      seminal vesicle ectasia, without resolution of pain symptoms. The patient was
      referred to us for persistent genitourinary infections, ejaculation disorder and
      episodes of gross hematuria. An additional MRI confirmed the presence of a cystic
      mass of 5,5 cm with a suspected opening into prostatic urethra. Urethrocystoscopy
      and urethrocystography retrograde confirmed this anatomical communication. For
      the persistence of the symptoms we performed retropubic surgical exeresis of the
      mass, with a histopathological finding of benign cyst of the vas deferens.? Two
      major postoperative complications were reported: a pelvic hematoma that required
      surgical exploration and a urinary extravasation at the level of prostatic
      urethra, which resolved with prolonged urethral catheterization.? CONCLUSIONS:
      Male pelvic floor cysts are a rare disease with a complex clinical and
      therapeutic management. A correct diagnosis is based on clinical signs and
      symptoms together with imaging studies of the pelvic region. The high risk of
      erectile dysfunction and ejaculatory disorders correlated to a surgical approach,
      recommend a treatment of these lesions only for symptomatic cases.

PMID- 24665032
TI  - Comparison of Contrast-Enhanced Ultrasound Scan (CEUS) and MRI in the follow-up
      of cryoablation for small renal tumors. Experience on 25 cases.
AB  - INTRODUCTION: Percutaneous ablation in the kidney is now performed as a standard
      therapeutic nephron-sparing option in patients who are poor candidates for
      resection. Its increasing use has been largely prompted by the rising incidental
      detection of renal cell carcinomas with cross-sectional imaging and the need to
      preserve renal function in patients with comorbid conditions, multiple renal cell
      carcinomas, and/or heritable renal cancer syndromes. To date, clinical studies
      indicate that cryoablation is an effective therapy with acceptable short- to
      intermediate-term outcomes and with a low risk in the appropriate setting. ?This
      article focuses on the efficiency of contrast enhanced ultrasound scan (CEUS) as
      compared to contrast enhanced magnetic resonance imaging (MRI) during the follow
      up after cryoablation of small renal tumors.? MATERIAL & METHODS: In our
      Department, percutaneous or laparoscopic assisted cryoablation is offered in the
      treatment of small renal masses. ?Between January 2009 and January 2013, 25
      patients (pts) were treated with laparoscopic assisted cryoablation or
      percutaneous cryoablation for renal tumors <3.5 cm in pts unfit for surgery. All
      pts had severe comorbidities (ASA score 3). Transperitoneal laparoscopic approach
      was performed in ?11 pts, extraperitoneal approach in 3 pts, percutaneous
      technique was performed in 11 patients. ?"Tru-cut biopsy" of the renal mass was
      always performed before cryoablation.? The SeedNet system (Galil Medical, Arden
      Hills, MN) was used in 12/25 pts; the Precise system (Galil Medical, Arden Hills,
      MN) was used in 13/25 pts. In all cases, IceRod needles were used. Real-time
      ultrasound guidance was used to localize the tumour and to monitor the
      progression of "iceball". A double "freeze-thaw cycle" was used. ?All pts had MRI
      and CEUS before cryoablation and the follow-up consisted in CEUS/MRI every ?3
      months during the first year and every 6 months thereafter.? RESULTS: The mean
      age of the 25 pts was 67.7 years (range 56-79); 5 pts were females and 20 were
      males. The mean tumor size was 2.8 cm (range 1.5-3.5). No patient required
      conversion to open procedure. 19 tumors were located at the lower pole, 4 were
      interpolar and 2 tumors were located at the upper pole. There were no
      intraoperative complications. The mean hospital stay was 4 days (range 1-7). Two
      pts required a blood transfusion; there was no statistically significant
      difference between preoperative and postoperative serum creatinine levels. The
      biopsy showed RCC in all cases. In 24/25 patients both CEUS and MRI showed no
      enhancement. In 1/25 pts, during the follow-up, CEUS and MRI showed a well
      visible recurrence at the perfusion study. It was histologically confirmed. The
      final results of CEUS and MRI were concordant in all pts. CONCLUSIONS: CEUS is
      effective during the follow-up of renal tumor cryoablation. It could be an
      alternative technique to standard CT and MRI, with some advantages: low cost,
      short time consuming procedure, no radiation exposure, reduced amount of contrast
      agent (1-2 mL) and rare adverse reactions.

PMID- 24665033
TI  - [History of laser in BPH therapy].
AB  - Laser technology has been used in the treatment of BPH for more than 15-20 years
      in order to challenge transurethral resection of the prostate. The aim of this
      review article is to analyze the evolution of laser in BPH therapy, from early
      coagulative techniques - progressively abandoned for their elevated postoperative
      morbidity and unfavorable outcomes - to the newer techniques of vaporization,
      resection and enucleation of the prostate. A better comprehension of tissue-laser
      interactions, the improvement of laser technology and a growing clinical
      experience have lead to the development of different laser systems (Holmium, KTP,
      Thulium laser) that challenge TURP. Today, HoLEP and, secondarily, PVP are the
      laser techniques supported by more clinical evidences and represent valid
      alternatives to TURP. 

PMID- 24665034
TI  - Multiple congenital anomalies-intellectual disability (MCA-ID) and neuroblastoma
      in a patient harboring a de novo 14q23.1q23.3 deletion.
AB  - Neuroblastoma is the most frequent extra cranial solid tumor in infants and
      children. Genetic predisposition to neuroblastoma has been suspected previously
      due to familial cases of sporadic NB and predisposition to NB in several
      syndromes. Here, we report on a de novo 14q23.1-q23.3 microdeletion in a male
      presenting with a neuroblastoma diagnosed at 9 months, and spherocytosis,
      congenital heart defect, cryptorchidism, hypoplasia of corpus callosum, epilepsy,
      and developmental delay. Myc-associated-factor X (MAX) haploinsufficiency could
      be regarded as the predisposing factor to NB. Indeed 14q deletion is a recurrent
      somatic rearrangement in NB and MAX somatic and germline loss of function
      mutation have recently been described in pheochromocytoma and paraganglioma.
      However, MAX was expressed in the tumor of the patient we report on and,
      accordingly, loss of heterozygosity, mutation, or promoter methylation were
      excluded. In addition, we discuss the potential involvement in the clinical
      spectrum presented by the patient of five of the deleted genes, namely DAAM1,
      PLEKHG3, SPTB, AKAP5, and ARID4A.

PMID- 24665036
TI  - The effectiveness of tetanus toxin on sciatic nerve regeneration: a preliminary
      experimental study in rats.
AB  - OBJECT: The purpose was to investigate the effects of local tetanus toxin (TeTx)
      application on sciatic nerve regeneration following a rat model of transection
      injury. METHODS: After both sciatic nerves were transected and repaired with
      three epineural sutures, 12 male Wistar albino rats were divided into two groups.
      0.25 ml (2.5 flocculation units) TeTx was injected into a piece of absorbable
      gelatin sponge in TeTx group. In controls, 0.25 ml saline injected. Assessments
      were performed by using climbing degrees, compound muscle action potentials
      (CMAPs) and histological parameters (axon number and axonal diameter) 12th week.
      RESULTS: CMAPs amplitudes were 11.6 +/- 4.7 mV and 1.4 +/- 1.3 mV in
      gastrocnemius and interdigital muscles in TeTx group (5.8 +/- 2.4 mV and 0.2 +/-
      0.1 mV, P < 0.05). Climbing degrees were significantly different (61.6 +/- 1.7
      vs. 38.3 +/- 2.6, P < 0.05). Total axon numbers were higher (1341.1 +/- 57.3 vs.
      877.5 +/- 34.9, P < 0.05) and the mean axon diameter was smaller (4.2 +/- 2.1 vs.
      2.5 +/- 1.9, P < 0.05) in the TeTx group. CONCLUSION: This preliminary study
      firstly demonstrated the effectiveness of TeTx on nerve repair in experimental
      sciatic rat model based on functional, electromyographic and histological
      parameters.

PMID- 24665035
TI  - Multifunctional PEGylated multiwalled carbon nanotubes for enhanced blood pool
      and tumor MR imaging.
AB  - Long-circulating multifunctional Gd(III)-loaded multiwalled carbon nanotubes
      (MWCNTs) modified with polyethylene glycol are designed and synthesized. The
      formed MWCNTs are water-dispersible, stable, and have good cytocompatibility and
      antifouling property. With the low r 2 /r 1 relaxivity ratio and relatively long
      blood circulation time, the multifunctional MWCNTs are able to be used as a
      platform for enhanced blood pool and tumor MR imaging. 

PMID- 24665037
TI  - Ernest Everett Just: Egg and embryo as excitable systems.
AB  - Ernest Everett Just (1883-1941) was an African American embryologist of
      international standing whose research interests lay in the area of fertilization
      and early development in marine invertebrates. Perhaps best known for his
      discovery of the dynamical and structural blocks to polyspermy that sweep over
      the egg upon fertilization, E. E. Just also was the first to associate cell
      surface changes with stages of embryonic development. He was deeply familiar with
      the natural history of the animals whose eggs he studied, and his knowledge of
      natural settings led him to emphasize the importance of using laboratory
      conditions that closely match those in nature. Based on more than 30 years of
      work, he came to believe that it was the cell surface that played the most
      critical role in development, heredity, and evolution. He promoted a holistic
      view of cells and organisms in opposition to the gene-centric view that was
      becoming more prevalent with the rise of genetics, but rejected the vitalism
      espoused by some biologists of his era, calling instead for "a physics and
      chemistry in a new dimension ...superimposed upon the now known physics and
      chemistry" to account for biological phenomena. Just's incisive critique of
      genetic reductionism finds echoes in contemporary multiscale, systems approaches
      in biology. His speculations on the relationship between developmental and
      evolutionary mechanisms resonate with today's evolutionary developmental biology.
      After a brief biographical sketch, this paper outlines and discusses some of
      Just's scientific contributions, and shows how his ideas remain relevant today.

PMID- 24665038
TI  - A new approach to prepare efficient blue AIE emitters for undoped OLEDs.
AB  - Two aggregation-induced emission active luminogens (TPE-pTPA and TPE-mTPA) were
      successfully synthesized. For comparison, another six similar compounds were
      prepared. Because of the introduced hole-dominated triphenylamine (TPA), fluorene
      groups with high luminous efficiency, and unconjugated linkages, the pi
      conjugation length of the obtained luminogens is effectively restricted to ensure
      their blue emission. The undoped organic light-emitting diodes based on TPE-pTPA
      and TPE-mTPA exhibited blue or deep-blue emissions, low turn-on voltages (3 V),
      and high electroluminescence efficiencies with Lmax, etaC,max, and etaP,max
      values of up to 26,697 cd m(-2), 3.37 cd A(-1), and 2.40 Lm W(-1).

PMID- 24665039
TI  - Near-infrared imaging for high-throughput screening of moisture induced changes
      in freeze-dried formulations.
AB  - Evaluation of freeze-dried biopharmaceutical formulations requires careful
      analysis of multiple quality attributes. The aim of this study was to evaluate
      the use of near-infrared (NIR) imaging for fast analysis of water content and
      related physical properties in freeze-dried formulations. Model formulations were
      freeze-dried in well plates. Samples were imaged with a NIR hyperspectral camera
      after freeze-drying and upon storage. On the basis of Karl Fischer titration
      reference values, a univariate quantification model was constructed and used to
      visualize the distribution of water within freeze-dried samples. Differences
      observed between samples stored at 11% and 43% relative humidity (RH) were found
      to be related to the amount of amorphous component in the sample. When stored at
      43% RH, the moisture content in samples with high sucrose content increased
      within 2 days and some degree of localized drying was observed within the samples
      after 3 days of storage. Further investigations with X-ray powder diffraction
      confirmed this local drying to be related to crystallization of sucrose. The
      combination of fast analysis of water content and spatial solid-state information
      makes NIR imaging a powerful tool for formulation development of freeze-dried
      samples.

PMID- 24665040
TI  - Nanomechanical measurement of astrocyte stiffness correlated with cytoskeletal
      maturation.
AB  - Astrocytes are known to serve as scaffolding cells that shape the brain. The
      physical properties of astrocytes, such as stiffness, are important for their
      scaffolding function. These properties may be altered in certain pathological
      conditions, such as in brain cancer. However, actual stiffness of astrocytes is
      not yet well understood. Here, we report that the astrocyte stiffness is
      positively correlated with the density of cytoskeletal proteins, such as actin
      filaments, microtubules, and intermediate filaments. The value of the stiffness
      of astrocytes as measured by atomic force microscopy (AFM) increases 38-fold in
      five-week-old rats compared to postnatal-day zero pups. Using multicolor confocal
      microscopy, we found that the complexity of cytoskeletal proteins, such as actin
      filaments, microtubules, and intermediate filaments, increase as the animal gets
      older. Our findings indicate that the change of stiffness positively correlates
      with the maturation of cytoskeletal proteins, and suggest that AFM can be useful
      as an analytical and diagnostic tool for neuroscience.

PMID- 24665042
TI  - Supramolecular proteoglycan aggregate mimics: cyclodextrin-assisted biodegradable
      polymer assemblies for electrostatic-driven drug delivery.
AB  - Self-assembled, noncovalent polymeric biodegradable materials mimicking
      proteoglycan aggregates were synthesized from inclusion complexes of cationic
      surfactants with gamma-cyclodextrin and the natural anionic polymer hyaluronan.
      The amorphous structure of this ternary system was proven by X-ray diffraction
      and thermal analysis. Light-scattering measurements showed that there was a
      competition between hyaluronic acid and the surfactant for the cyclodextrin
      cavity. These self-assembled supramolecular matrices were loaded with both
      hydrophilic and lipophilic drug substances for dissolution studies. The release
      of the entrapped drugs was found to be controlled by cations in the surrounding
      media and by biodegradation. Slow drug release in an ion-free medium became
      faster in physiological salt solution in which the macroscopic polymer matrix was
      disassembled. In contrast, the enzymatic degradation of hyaluronan was hindered
      in the polymeric matrix. The supramolecular systems consisting of gamma
      cyclodextrin as a macrocyclic host, a cationic surfactant guest, and hyaluronic
      acid as the anionic polymer electrostatically cross-linked by the inclusion
      complex of the first two was found to be a novel drug-delivery system for the
      controlled release of traditional drugs such as curcumin and ketotifen and
      proteins such as bovine serum albumin. 

PMID- 24665043
TI  - Eating disorders: when social rank perceptions are shaped by early shame
      experiences.
AB  - OBJECTIVES: Recent research has shown that early adverse experiences can be an
      important risk factor for eating disorders. However, the role of early shame
      memories and how they are structured as traumatic and central memories to self
      identity in eating disorders has never been investigated. This study explores the
      phenomenology of shame memories involving attachment figures and other agents
      from the wider social domain in patients with eating disorders, and examines the
      relationship between their traumatic and centrality features, social comparison
      based on physical appearance, and the severity of eating psychopathology. DESIGN:
      The study has a cross-sectional design using a structured interview to assess
      retrospective data. METHODS: Participants in this study were 36 patients with an
      eating disorder diagnosis, who were assessed using Eating Disorder Examination
      (EDE 16.0D), the Shame Experiences Interview (SEI), and self-report instruments
      measuring the traumatic features and centrality to identity of shame memories and
      social comparison. RESULTS: Results indicated that the traumatic and centrality
      qualities of shame memories involving social agents other than attachment figures
      (e.g., peers) are significantly correlated with unfavourable social rank
      perceptions and with increased eating psychopathology severity. Furthermore, the
      impact of such shame memories on eating psychopathology is fully mediated by
      social comparisons based on physical appearance. CONCLUSIONS: These findings
      highlight the importance of early shame experiences involving peers and other
      social agents that become traumatic memories, central to self-identity, to eating
      disorder patients' perceptions of inferiority and their core psychopathology
      features. PRACTITIONER POINTS: Early shame experiences of patients with eating
      disorders should be carefully assessed. Shame traumatic memories involving social
      agents outside the family circle (e.g., peers) seem to be especially damaging for
      patients with eating disorders, and influence how physical appearance is used as
      a central dimension to establish their social rank. Practitioners should directly
      work with these shame memories, focusing on diminishing their traumatic nature
      and reconstruct their central meaning to self-identity.

PMID- 24665044
TI  - Arsenic exposure through drinking water leads to senescence and alteration of
      telomere length in humans: A case-control study in West Bengal, India.
AB  - Arsenic (As) induces pre-malignant and malignant dermatological lesions, non
      dermatological health effects and cancers in humans. Senescence involves telomere
      length changes and acquisition of senescence-associated secretory phenotype
      (SASP), which promotes carcinogenesis. Though in vitro studies have shown that As
      induces senescence, population based studies are lacking. We investigated the
      arsenic-induced senescence, telomere length alteration and its contribution
      towards development of As-induced skin cancer. The study participants included 60
      each of As-exposed individuals with skin lesion (WSL), without skin lesions
      (WOSL) and 60 unexposed controls. Exposure assessment of drinking water and urine
      was done. SA beta-gal activity, ELISA, and quantification of senescence proteins,
      alternative lengthening of telomere (ALT) associated proteins and telomerase
      activity were performed. Relative telomere length (RTL) was determined by qPCR. A
      significantly higher number of senescent cells, over-expression of p53 and p21
      were observed in the As-exposed individuals when compared to unexposed. SASP
      markers, MMP-1/MMP-3 were significantly higher in the WSL but not IL-6/IL-8. A
      significant increase of RTL was observed in the WSL group, which was telomerase
      independent but exhibited an over-expression of ALT associated proteins TRF-1 and
      TRF-2 with higher increase in TRF-2. An increased risk for developing As-induced
      skin lesions was found for individuals having RTL greater than 0.827 (odds ratio,
      13.75; 95% CI: 5.66-33.41; P < 0.0001). Arsenic induces senescence in vivo, but
      the SASP markers are not strictly over-expressed in the As-induced skin lesion
      group, whereas telomerase-independent elongation of telomere length might be
      useful for predicting the risk of development of As-induced skin lesions.

PMID- 24665045
TI  - Human epithelial hair follicle stem cells and their progeny: current state of
      knowledge, the widening gap in translational research and future challenges.
AB  - Epithelial hair follicle stem cells (eHFSCs) are required to generate, maintain
      and renew the continuously cycling hair follicle (HF), supply cells that produce
      the keratinized hair shaft and aid in the reepithelialization of injured skin.
      Therefore, their study is biologically and clinically important, from alopecia to
      carcinogenesis and regenerative medicine. However, human eHFSCs remain ill
      defined compared to their murine counterparts, and it is unclear which murine
      eHFSC markers really apply to the human HF. We address this by reviewing current
      concepts on human eHFSC biology, their immediate progeny and their molecular
      markers, focusing on Keratin 15 and 19, CD200, CD34, PHLDA1, and EpCAM/Ber-EP4.
      After delineating how human eHFSCs may be selectively targeted experimentally, we
      close by defining as yet unmet key challenges in human eHFSC research. The
      ultimate goal is to transfer emerging concepts from murine epithelial stem cell
      biology to human HF physiology and pathology. 

PMID- 24665046
TI  - Production of human metabolites by gastrointestinal bacteria as a potential
      source of post-mortem alteration of antemortem drug/metabolite concentrations.
AB  - Previous studies have demonstrated that bacterial species are capable of
      transforming complex chemical substances. Several of these species, native to the
      human gastrointestinal tract, are active in postmortem decomposition. They have
      potential to cause biotransformations affecting compound-to-metabolite ratios
      within the human body, especially after death. Investigation of postmortem
      effects could supply valuable information, especially concerning compound
      identification and confirmation. The purpose of this research was to investigate
      the effects of Escherichia coli, Bacteroides fragilis, and Clostridium
      perfringens on diazepam and flunitrazepam in Reinforced Clostridial Medium, and
      to compare bacterial biotransformation products to those of human metabolism. A
      decrease in diazepam concentration between pre- and post-incubation was observed
      for samples inoculated with Escherichia coli (14.7-20.2%) as well as Bacteroides
      fragilis (13.9-25.7%); however there was no corresponding increase in
      concentration for the monitored human metabolites. Flunitrazepam demonstrated a
      greater concentration loss when incubated with individual bacterial species as
      well as mixed culture (79.2-100.0%). Samples incubated with Bacteroides fragilis,
      Clostridium perfringens, and mixed culture resulted in nearly complete conversion
      of flunitrazepam. Increased 7-aminoflunitrazepam concentrations accounted for the
      majority of the conversion; however discrepancies in the mass balance of the
      reaction suggested the possibility of a minor metabolite that was not monitored
      in the current analysis. These experiments served as a pilot study and proof of
      concept that can be adapted and applied to a realm of possibilities. Ultimately,
      this methodology would be ideal to study compounds that are too toxic or lethal
      for animal and human metabolic investigations.

PMID- 24665047
TI  - The role of surface functionality in nanoparticle exocytosis.
AB  - Getting out is just as important for nano-therapeutics as getting in. Exocytosis
      rates determine residency time in the cell, an important determinant for
      therapeutic efficacy and also for eventual clearance from the cell. In this
      study, it is shown that exocytosis efficiency is determined by surface
      functionality, providing a strategy for optimizing nanocarriers. 

PMID- 24665048
TI  - Rates of in vivo (arterial) and in vitro biocorrosion for pure magnesium.
AB  - The development of magnesium-based materials for bioabsorbable stents relies
      heavily on corrosion testing by immersion in pseudophysiological solutions, where
      magnesium degrades faster than it does in vivo. The quantitative difference in
      corrosion kinetics in vitro and in vivo is largely unknown, but, if determined,
      would help reduce dependence on animal models. In order to create a quantitative
      in vitro-in vivo correlation based on an accepted measure of corrosion
      (penetration rate), commercially pure magnesium wires were corroded in vivo in
      the abdominal aortas of rats for 5-32 days, and in vitro for up to 14 days using
      Dulbecco's modified eagle medium. Cross-sectioning, scanning electron microscopy,
      image analysis, a modified penetration rate tailored to degraded wires, and
      empirical modeling were used to analyze the corroded specimens. In vitro
      penetration rates were consistently higher than comparable in vivo rates by a
      factor of 1.2-1.9* (+/-0.2*). For a sample <20% corroded, an approximate in vitro
      in vivo multiplier of 1.3 +/- 0.2* was applied, whereas a multiplier of 1.8 +/-
      0.2* became appropriate when the magnesium specimen was 25-35% degraded.

PMID- 24665049
TI  - Development of a biomimetic phospholipid vesicle-based permeation assay for the
      estimation of intestinal drug permeability.
AB  - Permeability is a crucial property of orally administered drugs. Therefore, in
      drug discovery, it is important to employ methods suitable for rapidly and
      reliably screening the permeability of large numbers of new drug candidates. The
      phospholipid vesicle-based permeation assay (PVPA), a model consisting of a tight
      layer of liposomes immobilized on a filter, offers potential advantages unmet by
      other methods and has been successfully used in permeability testing of novel
      active substances as well as formulations. In this study, the PVPA was developed
      into a more robust, biomimetic model by employing a lipid composition matching
      that of the intestinal permeation barrier and performing the experiments at the
      more biologically relevant pH 6.2. As expected, positively charged basic
      compounds demonstrated increased permeability through the negatively charged
      biomimetic barriers, and the degree of correct classification according to in
      vivo absorption was comparable between the original PVPA and the biomimetic PVPA.
      The biomimetic PVPA further proved to be tremendously more robust toward the
      presence of tensides compared with the original PVPA; this is a promising finding
      that renders the biomimetic PVPA an enhanced ability to estimate the permeability
      of poorly soluble compounds. Hence, the PVPA model developed in this study has
      evolved an important step forward.

PMID- 24665050
TI  - Ultrafast dynamics of solvation and charge transfer in a DNA-based biomaterial.
AB  - Charge migration along DNA molecules is a key factor for DNA-based devices in
      optoelectronics and biotechnology. The association of a significant amount of
      water molecules in DNA-based materials for the intactness of the DNA structure
      and their dynamic role in the charge-transfer (CT) dynamics is less documented in
      contemporary literature. In the present study, we have used a genomic DNA
      cetyltrimethyl ammonium chloride (CTMA) complex, a technological important
      biomaterial, and Hoechest 33258 (H258), a well-known DNA minor groove binder, as
      fluorogenic probe for the dynamic solvation studies. The CT dynamics of CdSe/ZnS
      quantum dots (QDs; 5.2 nm) embedded in the as-prepared and swollen biomaterial
      have also been studied and correlated with that of the timescale of solvation. We
      have extended our studies on the temperature-dependent CT dynamics of QDs in a
      nanoenvironment of an anionic, sodium bis(2-ethylhexyl)sulfosuccinate reverse
      micelle (AOT RMs), whereby the number of water molecules and their dynamics can
      be tuned in a controlled manner. A direct correlation of the dynamics of
      solvation and that of the CT in the nanoenvironments clearly suggests that the
      hydration barrier within the Arrhenius framework essentially dictates the charge
      transfer dynamics. 

PMID- 24665051
TI  - Predictive risk factors of free flap thrombosis in breast reconstruction surgery.
AB  - Vascular thrombosis is one of the major postoperative complications of free flap
      microvascular breast reconstruction operations. It is associated with higher
      morbidity, higher cost, increased length of hospital stay, and potentially flap
      loss. Our purpose is to evaluate the rate of this complication and whether
      patient characteristics play a role. Using the Nationwide Inpatient Sample (NIS)
      database, we examined the clinical data of patients who underwent free flap
      breast reconstruction between 2009 and 2010 in the United States. Multivariate
      and univariate regression analyses were performed to identify independent risk
      factors of flap thrombosis. A total of 15,211 patients underwent free flap breast
      reconstruction surgery (immediate reconstruction: 43%). The most common flap was
      the free deep inferior epigastric perforator (DIEP) flap (53.6%), followed by
      free transverse rectus abdominis myocutaneous (TRAM) flap (43.1%), free
      superficial inferior epigastric artery (SIEA) flap (2%), and free gluteal artery
      perforator (GAP) flap (1.3%). The overall rate of flap thrombosis was 2.4 %, with
      the highest rate seen in the SIEA group (11.4%) and the lowest in the TRAM group
      (1.7%). Peripheral vascular disease (adjusted odds ration [AOR] 10.61), SIEA flap
      (AOR, 4.76) and delayed reconstruction (AOR, 1.42) were found to be statistically
      significant risk factors for flap thrombosis. Other comorbidities were not
      linked. While the overall rate of flap thrombosis in free flap breast
      reconstruction was relatively low (2.4%), Plastic Surgeons should be aware that
      patients with peripheral vascular disease and those undergoing free SIEA flap are
      at higher risk of flap thrombosis and they should closely monitor flaps to
      increase the chance for early salvage.

PMID- 24665052
TI  - Genetic counselor review of genetic test orders in a reference laboratory reduces
      unnecessary testing.
AB  - Genetic tests are routinely ordered by health care providers (HCPs) within a wide
      range of medical specialties. Many providers have limited knowledge or experience
      with ordering and interpreting genetic tests; thus, test order errors are common.
      Rigorous review of genetic test orders by genetic counselors (GCs) can provide a
      direct financial benefit to medical institutions, patients and insurers. GCs at
      ARUP (Associated Regional University Pathologists) Laboratories routinely perform
      a preanalytic assessment of complex molecular genetic test orders that includes
      reviewing clinical and family history information and considering the clinical
      utility and cost-effectiveness of ordered tests. GCs contact the ordering
      institution and/or HCP as needed to collect additional clinical information and
      confirm the test order or suggest alternative testing based on the provided
      information. A retrospective review of the GC-facilitated test changes over a 21
      month period at ARUP laboratories was performed. Approximately 26% of all
      requests for complex genetic tests assessing germ line mutations were changed
      following GC review. Testing fees associated with canceled tests were summed to
      estimate the cost-savings resulting from GC-facilitated test reviews. The test
      review process resulted in an average reduction in charges to the referring
      institutions of $48,000.00 per month. GC review of genetic test orders for
      appropriateness and clinical utility reduces healthcare costs to hospitals,
      insurers, and patients.

PMID- 24665053
TI  - Self management for patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Self management interventions help patients with chronic obstructive
      pulmonary disease (COPD) acquire and practise the skills they need to carry out
      disease-specific medical regimens, guide changes in health behaviour and provide
      emotional support to enable patients to control their disease. Since the first
      update of this review in 2007, several studies have been published. The results
      of the second update are reported here. OBJECTIVES: 1. To evaluate whether self
      management interventions in COPD lead to improved health outcomes.2. To evaluate
      whether self management interventions in COPD lead to reduced healthcare
      utilisation. SEARCH METHODS: We searched the Cochrane Airways Group Specialised
      Register of trials (current to August 2011). SELECTION CRITERIA: Controlled
      trials (randomised and non-randomised) published after 1994, assessing the
      efficacy of self management interventions for individuals with COPD, were
      included. Interventions with fewer than two contact moments between study
      participants and healthcare providers were excluded. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial quality and extracted
      data. Investigators were contacted to ask for additional information. When
      appropriate, study results were pooled using a random-effects model. The primary
      outcomes of the review were health-related quality of life (HRQoL) and number of
      hospital admissions. MAIN RESULTS: Twenty-nine studies were included. Twenty
      three studies on 3189 participants compared self management versus usual care;
      six studies on 499 participants compared different components of self management
      on a head-to-head basis. Although we included non-randomised controlled clinical
      trials as well as RCTs in this review, we restricted the primary analysis to RCTs
      only and reported these trials in the abstract.In the 23 studies with a usual
      care control group, follow-up time ranged from two to 24 months. The content of
      the interventions was diverse. A statistically relevant effect of self management
      on HRQoL was found (St George's Respiratory Questionnaire (SGRQ) total score,
      mean difference (MD) -3.51, 95% confidence interval (CI) -5.37 to -1.65, 10
      studies, 1413 participants, moderate-quality evidence). Self management also led
      to a lower probability of respiratory-related hospitalisation (odds ratio (OR)
      0.57, 95% CI 0.43 to 0.75, nine studies, 1749 participants, moderate-quality
      evidence). Over one year of follow-up, eight (95% CI 5 to 14) participants with a
      high baseline risk of respiratory-related hospital admission needed to be treated
      to prevent one participant with at least one hospital admission, and 20 (95% CI
      15 to 35) participants with a low baseline risk of hospitalisation needed to be
      treated to prevent one participant with at least one respiratory-related hospital
      admission.No statistically significant effect of self management on all-cause
      hospitalisation (OR 0.77, 95% CI 0.45 to 1.30, 6 studies, 1365 participants, low
      quality evidence) or mortality (OR 0.79, 95% CI 0.58 to 1.07, 8 studies, 2134
      participants, very low-quality evidence) was detected. Also, dyspnoea measured by
      the (modified) Medical Research Council Scale ((m)MRC) was reduced in individuals
      who participated in self management (MD -0.83, 95% CI -1.36 to -0.30, 3 studies,
      119 participants, low-quality evidence). The difference in exercise capacity as
      measured by the six-minute walking test was not statistically significant (MD
      33.69 m, 95% CI -9.12 to 76.50, 6 studies, 570 participants, very low-quality
      evidence). Subgroup analyses depending on the use of an exercise programme as
      part of the intervention revealed no statistically significant differences
      between studies with and without exercise programmes in our primary outcomes of
      HRQoL and respiratory-related hospital admissions.We were unable to pool head-to
      head trials because of heterogeneity among interventions and controls; thus
      results are presented narratively within the review. AUTHORS' CONCLUSIONS: Self
      management interventions in patients with COPD are associated with improved
      health-related quality of life as measured by the SGRQ, a reduction in
      respiratory-related hospital admissions, and improvement in dyspnoea as measured
      by the (m)MRC. No statistically significant differences were found in other
      outcome parameters. However, heterogeneity among interventions, study
      populations, follow-up time and outcome measures makes it difficult to formulate
      clear recommendations regarding the most effective form and content of self
      management in COPD.

PMID- 24665055
TI  - Genomics, evolution and development of amphioxus and tunicates: The Goldilocks
      principle.
AB  - Morphological comparisons among extant animals have long been used to infer their
      long-extinct ancestors for which the fossil record is poor or non-existent. For
      evolution of the vertebrates, the comparison has typically involved amphioxus and
      vertebrates. Both groups are evolving relatively slowly, and their genomes share
      a high level of synteny. Both vertebrates and amphioxus have regulative
      development in which cell fates become fixed only gradually during embryogenesis.
      Thus, their development fits a modified hourglass model in which constraints are
      greatest at the phylotypic stage (i.e., the late neurula/early larva), but are
      somewhat greater on earlier development than on later development. In contrast,
      the third group of chordates, the tunicates, which are sister group to
      vertebrates, are evolving rapidly. Constraints on evolution of tunicate genomes
      are relaxed, and they have discarded key developmental genes and organized much
      of their coding sequences into operons, which are transcribed as a single mRNA
      that undergoes trans-splicing. This contrasts with vertebrates and amphioxus,
      whose genomes are not organized into operons. Concomitantly, tunicates have
      switched to determinant development with very early fixation of cell fates. Thus,
      tunicate development more closely fits a progressive divergence model (shaped
      more like a wine glass than an hourglass) in which the constraints on the zygote
      and very early development are greatest. This model can help explain why tunicate
      body plans are so very diverse. The relaxed constraints on development after
      early cleavage stages are correlated with relaxed constraints on genome
      evolution. The question remains: which came first?

PMID- 24665054
TI  - Relationship between gestational fasting plasma glucose and neonatal birth
      weight, prenatal blood pressure and dystocia in pregnant Chinese women.
AB  - BACKGROUND: Little is known about the optimal cut-off point of fasting plasma
      glucose for the diagnosis of gestational diabetes mellitus for pregnant Chinese
      women. This study investigates the relationship between gestational fasting
      plasma glucose and several variables: neonatal birth weight, prenatal blood
      pressure and dystocia rate of pregnant women. In this study, we hoped to provide
      a useful tool to screen gestational diabetes mellitus in pregnant Chinese women.
      METHODS: For 1058 pregnant women enrolled in our hospital at pregnancy weeks 22
      30, fasting plasma glucose, neonatal birth weight and prenatal blood pressure, as
      well as dystocia conditions, were examined. We analysed the correlations between
      the following: gestational fasting plasma glucose and neonatal birth weight;
      prenatal blood pressure and gestational fasting plasma glucose as well as
      dystocia rate and gestational fasting plasma glucose group. RESULTS: A modest
      correlation was observed between gestational fasting plasma glucose and neonatal
      birth weight (r = 0.093, p = 0.003). The macrosomia rate was smallest when the
      gestational fasting plasma glucose was in the range 3.51-5.5 mmol/L. Prenatal
      blood pressure increased linearly with increasing gestational fasting plasma
      glucose (p = 0.000). There was a significant difference between the dystocia
      rates in different fasting plasma glucose groups (chi-squared = 13.015, p =
      0.043). The results showed that the dystocia rate significantly increased when
      gestational fasting plasma glucose was >4.9 mmol/L; p = 0.03, OR = 2.156 (95% CI,
      1.077-4.318). CONCLUSION: We suggest that the optimal range of gestational
      fasting plasma glucose for pregnant Chinese women is in the range 3.5-4.9 mmol/L.

PMID- 24665056
TI  - Thermal- and photo-induced phase-transition behaviors of a tapered dendritic
      liquid crystal with photochromic azobenzene mesogens and a bicyclic chiral
      center.
AB  - A ribbon-shaped chiral liquid crystalline (LC) dendrimer with photochromic
      azobenzene mesogens and an isosorbide chiral center (abbreviated as AZ3 DLC) was
      successfully synthesized and its major phase transitions were studied by using
      differential scanning calorimetry (DSC) and linear polarized optical microscopy
      (POM). Its ordered structures at different temperatures were further identified
      through structure-sensitive diffraction techniques. Based on the experimental
      results, it was found that the AZ3 DLC molecule exhibited the low-ordered chiral
      smectic (Sm*) LC phase with 6.31 nm periodicity at a high-temperature phase
      region. AZ3 DLC showed the reversible photoisomerization in both organic solvents
      and nematic (N) LC media. As a chiral-inducing agent, it exhibited a good
      solubility, a high helical-twisting power, and a large change in the helical
      twisting power due to its photochemical isomerization in the commercially
      available N LC hosts. Therefore, we were able to reversibly "remote-control" the
      colors in the whole visible region by finely tuning the helical pitch of the
      spontaneously formed helical superstructures. 

PMID- 24665060
TI  - Genome-wide association study of smoking behaviours among Bangladeshi adults.
AB  - BACKGROUND: The high prevalence of tobacco use in some developing nations,
      including Bangladesh, poses several public health challenges for these
      populations. Smoking behaviour is determined by genetic and environmental
      factors; however, the genetic determinants of smoking behaviour have not been
      previously examined in a Bangladeshi or South Asian population. We performed a
      genome-wide association study (GWAS) of tobacco smoking behaviour among a
      population-based sample of 5354 (2035 ever smokers and 3319 never smokers) men
      and women in Bangladesh. METHODS: Genome-wide association analyses were conducted
      for smoking initiation (ever vs never smokers), smoking quantity (cigarettes per
      day), age of smoking initiation, and smoking cessation (former vs current
      smokers). Sex-stratified associations were performed for smoking initiation.
      RESULTS: We observed associations for smoking initiation in the SLC39A11 region
      at 17q21.31 (rs2567519, p=1.33*10-7) among men and in the SLCO3A1 region at 15q26
      (rs12912184, p=9.32*10-8) among women. CONCLUSIONS: These findings suggest
      possible underlying mechanisms related to solute carrier transporter genes, which
      transport neurotransmitters, nutrients, heavy metals and other substrates into
      cells, for smoking initiation in a South Asian population in a sex-specific
      pattern. Genetic markers could have potential translational implications for the
      prevention or treatment of tobacco use and addiction in South Asian populations
      and warrant further exploration.

PMID- 24665059
TI  - Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese
      population.
AB  - BACKGROUND: Elucidating the genetic basis underlying hepatic gene expression
      variability is of importance to understand the aetiology of the disease and
      variation in drug metabolism. To date, no genome-wide expression quantitative
      trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the
      largest ethnic group in the world. METHODS: We performed a genome-wide eQTL
      mapping in a set of Han Chinese liver tissue samples (n=64). The data were then
      compared with published eQTL data from a Caucasian population. We then performed
      correlations between these eQTLs with important pharmacogenes, and genome-wide
      association study (GWAS) identified single nucleotide polymorphisms (SNPs), in
      particular those identified in the Asian population. RESULTS: Our analyses
      identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found
      that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide
      significance level (p=10-8). Both cis- and trans-eQTLs in the Asian population
      were also more likely to be eQTLs in Caucasians (p<10-4). Enrichment analyses
      revealed that trait-associated GWAS-SNPs were enriched within the eQTLs
      identified in our data, so were the GWAS-SNPs specifically identified in Asian
      populations in a separate analysis (p<0.001 for both). We also found that hepatic
      expression of very important pharmacogenetic (VIP) genes (n=44) and a manually
      curated list of major genes involved in pharmacokinetics (n=341) were both more
      likely to be controlled by eQTLs (p<0.002 for both). CONCLUSIONS: Our study
      provided, for the first time, a comprehensive hepatic eQTL analysis in a non
      European population, further generating valuable data for characterising the
      genetic basis of human diseases and pharmacogenetic traits.

PMID- 24665061
TI  - Mesoporous silica-coated plasmonic nanostructures for surface-enhanced Raman
      scattering detection and photothermal therapy.
AB  - The design and fabrication of core-shell and yolk-shell nanostructures with
      surface plasmon resonance (SPR)-active center protected by permeable mesoporous
      channels can raise the new vitality into the catalysis and biological
      applications. Hybrid plasmonic-mesoporous silica nanocarriers consisting of Ag
      and Au-Ag alloy nanoparticles are fabricated through spatially confined galvanic
      replacement approach. The plasmonic absorption peaks can be finely controlled to
      the near-infrared (NIR) region (500-790 nm) that is beneficial for tissue
      transmittance. The mesoporous silica shell facilitates also protection of Au-Ag
      cores and affords the channels between the exterior and interior capsule
      environments, thereby endowing the multiple applications. In the present work, it
      is successfully demonstrated that mesoporous silica-coated Au-Ag alloy core-shell
      and yolk-shell nanocarriers can serve as good substrates for surface-enhanced
      Raman scattering (SERS) detection. The SERS signal intensities of nanocarriers
      are highly dependent on the SPR peaks and the contents of gold. Simultaneously,
      the synthesized Au-Ag@mSiO2 nanocarriers with SPR peak at ~790 nm can be applied
      in NIR-sensitive SERS detection and photothermal therapy. 

PMID- 24665062
TI  - Effects of novel hydroxyapatite-based 3D biomaterials on proliferation and
      osteoblastic differentiation of mesenchymal stem cells.
AB  - The aim of this study was to examine the differential capacity of isolated dental
      pulp stem cells (SHED) cultured onto four different scaffold materials. The
      differential potential of isolated SHED was examined on the following scaffolds:
      porous hydroxyapatite (pHAP) alone or combined with three polymers [polylactic-co
      glycolic acid (PLGA), alginate, and ethylene vinylacetate / ethylene
      vinylversatate (EVA/EVV)]. SHED were isolated by "outgrowth" method and
      characterized by the flow cytometry. Viability of cells grown with scaffolds was
      assessed by MTT and LDH assays. No significant cytotoxic effect of any of the
      tested materials was shown. Staining with alizarin red and estimated alkaline
      phosphatase activity to identify differentiation, demonstrated osteoblastic
      phenotype of SHED and newly deposited and mineralized extra cellular matrix (ECM)
      in presence of all tested scaffolds. The developed ECM seen at scanning
      electronic micrographs additionally confirmed the osteogenic differentiation and
      biocompatibility between cells and materials. In summary, all studied
      biomaterials are suitable carriers for proliferation and osteoblastic
      differentiation of dental pulp mesenchymal stem cells in vitro.

PMID- 24665063
TI  - Loss of SMAD4 staining in pre-operative cell blocks is associated with distant
      metastases following pancreaticoduodenectomy with venous resection for pancreatic
      cancer.
AB  - BACKGROUND AND OBJECTIVES: Venous resection of locally advanced pancreatic cancer
      is associated with increased morbidity and mortality; therefore identification of
      patients most likely to benefit from this aggressive surgical approach is an
      important goal. Loss of SMAD4 staining on resected specimens has been associated
      with outcomes. Few studies have evaluated the prognostic significance of SMAD4
      staining of pre-operative cell blocks, which would be useful in clinical decision
      making for patients with locally advanced disease. METHODS: Clinical data were
      retrospectively evaluated from all patients undergoing pancreaticoduodenectomy
      with venous resection. Immunohistochemical staining for SMAD4 was performed on
      pre-operative cell blocks and subsequent post-operative resections. RESULTS: One
      hundred seventeen patients underwent pancreaticoduodenectomy with venous
      resection. Sixty had sufficient specimens available for SMAD4 staining. SMAD4
      loss was observed in 70% of resections and was associated with earlier time to
      metastatic disease. Pre-operative SMAD4 loss correlated well with post-operative
      staining and was associated with six times higher likelihood of developing
      metastases. CONCLUSION: In this pilot study, preoperative SMAD4 staining showed a
      strong correlation with postoperative staining and predicted metastases in
      locally advanced cancer. Preoperative SMAD4 status may be considered as one of
      several factors when selecting patients most likely to benefit from aggressive en
      bloc venous resection.

PMID- 24665064
TI  - A survey of microsurgery training among UK plastic surgery and maxillofacial
      surgery trainees.

PMID- 24665065
TI  - Segmental overgrowth syndrome due to an activating PIK3CA mutation identified in
      affected muscle tissue by exome sequencing.
AB  - Mosaic PIK3CA-mutations have been described in an increasing number of overgrowth
      syndromes. We describe a patient with a previously unreported segmental
      overgrowth syndrome with the mutation, PIKCA3 c.3140A>G (p.His1047Arg) in
      affected tissue diagnosed by exome sequencing. This PIK3CA-associated segmental
      overgrowth syndrome overlaps with CLOVES syndrome and fibroadipose hyperplasia
      but is distinct from each of these entities.

PMID- 24665066
TI  - Effect of various intercalators on the fenton-type oxidative cleavage of double
      stranded DNA.
AB  - The intensity of the linear dichroism (LD) in the absorption region of DNA (about
      260 nm) decreased with time in the presence of [Fe(EDTA)](2+) (EDTA =
      ethylenediaminetetraacetic acid), H2O2, and ascorbate. The decrease in the LD
      signal indicated either an increase in flexibility, a shortening of the DNA stem,
      or both, owing to oxidative cleavage, and was best described by the difference
      between the two single-exponential-decay curves, thereby suggesting the
      involvement of two sequential first-order reactions. The fast reaction was
      assigned to cleavage of one of two DNA strands, which increased the flexibility
      of the DNA. The slow reaction corresponded to cleavage at or near the first
      cleavage site, thereby shortening the DNA stem. The presence of an intercalator,
      including ethidium, propidium, 9-aminoacridine, and proflavine, inhibited the
      first step of the cleavage reaction. One of the possible reasons for the observed
      inhibition might be a change in the DNA conformation near the intercalation site.
      Intercalation caused an unwinding and elongation of the DNA and resulted in
      changes in the location of the H atoms of the sugar moiety, which is known to be
      the main site at which hydroxyl radicals react.

PMID- 24665067
TI  - Bioinspired carbon nanotube fuzzy fiber hair sensor for air-flow detection.
AB  - Artificial hair sensors consisting of a piezoresistive carbon-nanotube-coated
      glass fiber embedded in a microcapillary are assembled and characterized.
      Individual sensors resemble a hair plug that may be integrated in a wide range of
      host materials. The sensors demonstrate an air-flow detection threshold of less
      than 1 m/s with a piezoresistive sensitivity of 1.3% per m/s air-flow change. 

PMID- 24665068
TI  - Using standardized videos to validate a measure of handoff quality: the handoff
      mini-clinical examination exercise.
AB  - BACKGROUND: The most recent iteration of the Accreditation Council for Graduate
      Medical Education duty-hour regulations includes language mandating handoff
      education for trainees and assessments of handoff quality by residency training
      programs. However, there is a lack of validated tools for the assessment of
      handoff quality and for use in trainee education. METHODS: Faculty at 2 sites
      (University of Chicago and Yale University) were recruited to participate in a
      workshop on handoff education. Video-based scenarios were developed to represent
      varying levels of performance in the domains of communication, professionalism,
      and setting. Videos were shown in a random order, and faculty were instructed to
      use the Handoff Mini-Clinical Examination Exercise (CEX), a paper-based
      instrument with qualitative anchors defining each level of performance, to rate
      the handoffs. RESULTS: Forty-seven faculty members (14 at site 1; 33 at site 2)
      participated in the validation workshops, providing a total of 172 observations
      (of a possible 191 [96%]). Reliability testing revealed a Cronbach alpha of 0.81
      and Kendall coefficient of concordance of 0.59 (>0.6 = high reliability). Faculty
      were able to reliably distinguish the different levels of performance in each
      domain in a statistically significant fashion (ie, unsatisfactory professionalism
      mean 2.42 vs satisfactory professionalism 4.81 vs superior professionalism 6.01,
      P < 0.001 trend test). Two-way analysis of variance revealed no evidence of rater
      bias. CONCLUSIONS: Using standardized video-based scenarios highlighting
      differing levels of performance, we were able to demonstrate evidence that the
      Handoff Mini-CEX can draw reliable and valid conclusions regarding handoff
      performance. Future work to validate the tool in clinical settings is warranted.

PMID- 24665069
TI  - Animal models of spondyloarthritis: do they faithfully mirror human disease?

PMID- 24665070
TI  - Kilogram-scale production of SnO(2) yolk-shell powders by a spray-drying process
      using dextrin as carbon source and drying additive.
AB  - A simple and general method for the large-scale production of yolk-shell powders
      with various compositions by a spray-drying process is reported. Metal
      salt/dextrin composite powders with a spherical and dense structure were obtained
      by spray drying and transformed into yolk-shell powders by simple combustion in
      air. Dextrin plays a key role in the preparation of precursor powders for
      fabricating yolk-shell powders by spray drying. Droplets containing metal salts
      and dextrin show good drying characteristics even in a severe environment of high
      humidity. Sucrose, glucose, and polyvinylpyrrolidone are widely used as carbon
      sources in the preparation of metal oxide/carbon composite powders; however, they
      are not appropriate for large-scale spray-drying processes because of their
      caramelization properties and adherence to the surface of the spray dryer. SnO2
      yolk-shell powders were studied as the first target material in the spray-drying
      process. Combustion of tin oxalate/dextrin composite powders at 600  degrees C in
      air produced single-shelled SnO2 yolk-shell powders with the configuration SnO2
      @void@SnO2 . The SnO2 yolk-shell powders prepared by the simple spray-drying
      process showed superior electrochemical properties, even at high current
      densities. The discharge capacities of the SnO2 yolk-shell powders at a current
      density of 2000 mA g(-1) were 645 and 570 mA h g(-1) for the second and 100th
      cycles, respectively; the corresponding capacity retention measured for the
      second cycle was 88 %. 

PMID- 24665071
TI  - Percutaneous vertebroplasty for painful spinal metastasis with epidural
      encroachment.
AB  - BACKGROUND AND OBJECTIVES: Spinal metastasis with epidural encroachment is
      regarded by several authors to be a contraindication to percutaneous
      vertebroplasty (PVP) because of the risk of increasing symptomatic leakage of
      cement. This analysis aims to evaluate the safety and efficacy of PVP in patients
      with painful spinal metastasis and encroachment of epidural space. METHODS: A
      retrospective study was conducted to review 43 consecutive patients with spinal
      metastasis that underwent PVP, for a total of 69 affected levels. All patients
      had at least 1 level associated with epidural encroachment related to metastasis.
      Among these patients, 14 had signs of spinal cord or cauda equina compression.
      Pain intensity was scored on a visual-analog scale (VAS). The analgesic efficacy
      was defined as at least 50% improvement in pain score as compared with the pre
      procedure baseline and post-procedure. Clinical improvement of neurological
      compressive symptoms was defined as a decrease in ASIA impairment scale from
      baseline of 1 point or more. RESULTS: The analgesic efficacy was achieved in
      89.7% of survival patients at 1 month, 87.5% at 3 months, 86.9% at 6 months, and
      84.6% at 1 year. Small amount cement leakages were detected in 69.6% of treated
      levels without clinical complications. No deterioration of spinal cord or cauda
      equina compression symptoms was observed after a PVP in any patients. The
      different grade of epidural encroachment of the lesions was not correlated with
      filling volume or extraosseous leakage (P > 0.05). The treated levels with
      epidural encroachment showed a statistically significant relationship to spinal
      canal leakage (P < 0.05). CONCLUSIONS: PVP can be performed safely and
      effectively in patients with painful spinal metastasis and epidural encroachment.

PMID- 24665073
TI  - Adapted chondrogenic differentiation of human mesenchymal stem cells via
      controlled release of TGF-beta1 from poly(ethylene oxide)
      terephtalate/poly(butylene terepthalate) multiblock scaffolds.
AB  - Controlled release of TGF-beta1 from scaffolds is an attractive mechanism to
      modulate the chondrogenesis of human bone marrow mesenchymal stem cells (hBMSCs)
      that repopulate articular cartilage defects. Here, we evaluated the ability of
      porous scaffolds composed of poly(ethylene oxide)-terephtalate and poly(butylene
      terepthalate) (PEOT/PBT) to release bioactive TGF-beta1 for chondrogenesis of
      hBMSCs in a pellet culture model. Chondroinduction was compared with that
      promoted by direct addition of the recombinant factor to the culture medium. The
      data show a controlled release of TGF-beta1 from scaffolds for at least 21 days
      in vitro, with ~10% of TGF-beta1 released during this period. The delivered TGF
      beta1 was bioactive, as confirmed by successful chondrogenic differentiation of
      hBMSCs monitored by morphological, histological, immunohistochemical,
      biochemical, and real-time reverse transcription polymerase chain reaction
      analyses. Third, semiquantitative histological evaluations revealed a similar
      pattern of chondrogenesis compared with the positive controls. Importantly, TGF
      beta1-loaded scaffolds allowed for a ~700-fold upregulation of type-II collagen
      mRNA compared to when pellets were maintained in the presence of the soluble TGF
      beta1, reflected also in the highest score of immunoreactivity to type-II
      collagen, not significantly different from the positive controls. Likewise,
      aggrecan mRNA was ~200-fold upregulated. Interestingly, most (>94%) of the
      glycosaminoglycan produced remaining associated with the pellets. Analysis of
      hypertrophic events showed no significant difference in the average total
      hypertrophy score compared with the positive controls. These results demonstrate
      the suitability of controlled TGF-beta1 release from biocompatible scaffolds to
      promote hBMSC chondrogenesis at a physical distance and in the absence of soluble
      TGF-beta1.

PMID- 24665072
TI  - Modeling AEC-New approaches to study rare genetic disorders.
AB  - Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare
      monogenetic disorder that is characterized by severe abnormalities in ectoderm
      derived tissues, such as skin and its appendages. A major cause of morbidity
      among affected infants is severe and chronic skin erosions. Currently, supportive
      care is the only available treatment option for AEC patients. Mutations in TP63,
      a gene that encodes key regulators of epidermal development, are the genetic
      cause of AEC. However, it is currently not clear how mutations in TP63 lead to
      the various defects seen in the patients' skin. In this review, we will discuss
      current knowledge of the AEC disease mechanism obtained by studying patient
      tissue and genetically engineered mouse models designed to mimic aspects of the
      disorder. We will then focus on new approaches to model AEC, including the use of
      patient cells and stem cell technology to replicate the disease in a human tissue
      culture model. The latter approach will advance our understanding of the disease
      and will allow for the development of new in vitro systems to identify drugs for
      the treatment of skin erosions in AEC patients. Further, the use of stem cell
      technology, in particular induced pluripotent stem cells (iPSC), will enable
      researchers to develop new therapeutic approaches to treat the disease using the
      patient's own cells (autologous keratinocyte transplantation) after correction of
      the disease-causing mutations.

PMID- 24665074
TI  - M-shaped grating by nanoimprinting: a replicable, large-area, highly active
      plasmonic surface-enhanced Raman scattering substrate with nanogaps.
AB  - Plasmonic nanostructures separated by nanogaps enable strong electromagnetic
      field confinement on the nanoscale for enhancing light-matter interactions, which
      are in great demand in many applications such as surface-enhanced Raman
      scattering (SERS). A simple M-shaped nanograting with narrow V-shaped grooves is
      proposed. Both theoretical and experimental studies reveal that the
      electromagnetic field on the surface of the M grating can be pronouncedly
      enhanced over that of a grating without such grooves, due to field localization
      in the nanogaps formed by the narrow V grooves. A technique based on room
      temperature nanoimprinting lithography and anisotropic reactive-ion etching is
      developed to fabricate this device, which is cost-effective, reliable, and
      suitable for fabricating large-area nanostructures. As a demonstration of the
      potential application of this device, the M grating is used as a SERS substrate
      for probing Rhodamine 6G molecules. Experimentally, an average SERS enhancement
      factor as high as 5*108 has been achieved, which verifies the greatly enhanced
      light-matter interaction on the surface of the M grating over that of traditional
      SERS surfaces.

PMID- 24665075
TI  - H-shaped oligofluorenes for highly air-stable and low-threshold non-doped deep
      blue lasing.
AB  - H-shaped oligofluorenes as gain media exhibit excellent photo- (large robustness
      against oxidation) and thermal stabilities in ambient atmosphere for large sigmae
      and low-threshold (0.22 nJ pulse(-1) ) deep blue distributed feedback (DFB)
      lasers. Their amplified spontaneous emission (ASE) thresholds increase less than
      3-fold and the emission spectra exhibit almost no shift with film samples
      annealed up to 200  degrees C in open air. 

PMID- 24665080
TI  - Spontaneous H2 loss through the interaction of squaric acid derivatives and BeH2.
AB  - The most stable complexes between squaric acid and its sulfur- and selenium
      containing analogues (C4X4H2 ; X = O, S, Se) with BeY2 (Y = H, F) were studied by
      means of the Gaussian 04 (G4) composite ab initio theory. Squaric acid
      derivatives are predicted to be very strong acids in the gas phase; their acidity
      increases with the size of the chalcogen, with C4Se4H2 being the strongest acid
      of the series and stronger than sulfuric acid. The relative stability of the
      C4X4H2?BeY2 (X = O, S, Se; Y = H, F) complexes changes with the nature of the
      chalcogen atom; but more importantly, the formation of the C4X4H2?BeF2 complexes
      results in a substantial acidity enhancement of the squaric moiety owing to the
      dramatic electron-density redistribution undergone by the system when the
      beryllium bond is formed. The most significant consequence of this acidity
      enhancement is that when BeF2 is replaced by BeH2, a spontaneous exergonic loss
      of H2 is observed regardless of the nature of the chalcogen atom. This is another
      clear piece of evidence of the important role that closed-shell interactions play
      in the modulation of physicochemical properties of the Lewis acid and/or the
      Lewis base.

PMID- 24665079
TI  - Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their
      frequency is influenced by disease duration and therapy.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is thought to be a T cell-mediated disease,
      based on its strong association with HLA class II alleles, clinical
      responsiveness to T cell-directed therapies, and the presence of CD4+ T cells in
      rheumatoid joints. The presence of anti-citrullinated protein antibodies (ACPAs)
      in RA serum and the association of these antibodies with HLA-DR4 alleles
      implicate citrulline-specific autoreactive T cells in the development and
      progression of RA. The goal of this study was to determine the characteristics
      and specificity of autoreactive T cell responses in RA. METHODS: We developed a
      panel of HLA-DRB1*04:01 tetramers, selecting citrullinated peptides from synovial
      antigens and verifying their immunogenicity in DRB1*04:01-transgenic mice. Seven
      tetramers were used to examine the ex vivo frequency and surface phenotype of
      citrulline-specific (Cit-specific) T cells in patients with RA and healthy
      subjects with DRB1*04:01 haplotypes, using a magnetic enrichment procedure.
      RESULTS: Cit-specific T cells were detectable in peripheral blood samples from
      both healthy subjects and RA patients. In comparison to healthy subjects, RA
      patients had significantly higher frequencies of Cit-specific T cells, and a
      greater proportion of these cells displayed a Th1 memory phenotype. Among RA
      patients, the frequency of Cit-specific T cells was highest within the first 5
      years after diagnosis of RA and was decreased in patients taking biologic agents,
      irrespective of disease duration. CONCLUSION: These findings link the presence of
      ACPAs in RA with Th1 cells specific for citrullinated epitopes and provide tools
      for disease-specific immunomonitoring of autoreactive T cells.

PMID- 24665081
TI  - The intellectual disabilities evaluation and advice system (IDEAS): outcome of
      the first 55 cases.
AB  - IDEAS (intellectual disabilities evaluation and advice system) provides the
      opportunity for physicians who are sending samples for the Greenwood Genetic
      Center (GGC) 92-gene X-linked intellectual disability (XLID) (formerly X-linked
      mental retardation) panel to have their male patient's clinical features reviewed
      by an experienced panel of six Clinical Geneticists. They were asked to obtain
      parental consent, complete a one-page information form, and provide A-P and
      lateral photographs. The panel members independently reviewed the material and
      forwarded comments about clinical features, possible diagnoses, and/or further
      testing for the patient. We present the results of the first 55 patients
      evaluated. In only a single case did all panelists agree on a non-XLID diagnosis,
      later proven by genetic testing. The XLID gene panel diagnosed an additional five
      (9%) cases, but in only two cases did one panelist suggest the correct gene,
      which was one of four they suggested. This paper examines the possible reasons
      for the low rate of clinical diagnosis and suggests that, while the data received
      were often incomplete, the most important reasons for lack of diagnoses were the
      source of referral and selection of patients for review. We did note that there
      were a number of instances where we disagreed with the submitted information as
      to whether the individual was dysmorphic and with the stated presence of certain
      physical signs, most often downslanted palpebrae and posterior ear angulation.
      These differences in assessment of clinical signs and the general lack of
      completeness and detail provided in the standard data sheet, including that
      regarding the extended family history, lead us to raise concerns regarding the
      feasibility of establishing high quality central clinical databases designed to
      aid in the interpretation of exomic/genomic variants.

PMID- 24665082
TI  - The impact of the distance from the interventional cardiologist's home to the
      hospital during off hours.
AB  - OBJECTIVES: The impact of the distance from the interventional cardiologist's
      home to the hospital and door to balloon time (DTBT) BACKGROUND: The importance
      of DTBT is highlighted by its inclusion as one of the core quality measures
      collected by the center for Medicare and Medicaid services and by the Joint
      commission on Accreditation of Healthcare organizations. We investigated the
      effect of time of day on the DTBT in patients having primary percutaneous
      coronary intervention (pPCI) and the impact of distance of the on call
      interventional cardiologist from the hospital on the DTBT and major adverse
      cardiac events (MACE) in patients undergoing pPCI during the off hours METHODS:
      Patients enrolled in the study presented with STEMI either in the field or to the
      emergency department (ED) and underwent pPCI from October 2007 to July 2009
      RESULTS: Significant predictors of DTBT included a history of prior MI (P =
      0.001), prior percutaneous coronary intervention (P = 0.021), prior coronary
      artery bypass grafting (P < 0.001), and history of diabetes mellitus (P = 0.004).
      The strongest predictor of DTBT was on versus off hours. Mean DTB was 18.5 min
      greater during off hours (72 min) compared to on-hours (53.5 min). The distance
      from the cardiologist's home to the hospital was not associated with DTBT on
      multivariable analysis (P = 0.20) CONCLUSION: When pPCI is performed in a highly
      organized STEMI center with broad staff support and expertise in cardiac care,
      the increase in the DTBT during off hours was not associated with increase MACE
      rates.

PMID- 24665084
TI  - Correlated coordination and redox activity of a hemilabile noninnocent ligand in
      nickel complexes.
AB  - The compound [Ni(QM)2], QM = 4,6-di-tert-butyl-N-(2-methylthiomethylphenyl)-o
      iminobenzoquinone, is a singlet diradical species with approximately planar
      configuration at the tetracoordinate metal atom and without any Ni-S bonding
      interaction. One-electron oxidation results in additional twofold Ni-S
      coordination (dNi-S ~2.38 A) to produce a complex cation of [Ni(QM)2](PF6) with
      hexacoordinate Ni(II) and two distinctly different mer-configurated tridentate
      ligands. The O,O'-trans arrangement in the neutral precursor is changed to an
      O,O'-cis configuration in the cation. The EPR signal of [Ni(QM)2](PF6) has a very
      large g anisotropy and the magnetic measurements indicate an S = 3/2 state. The
      dication was structurally characterized as [Ni(QM)2](ClO4)2 to exhibit a similar
      NiN2O2S2 framework as the monocation. However, the two tridentate (O,N,S) ligands
      are now equivalent according to the formulation [Ni(II)(QM(0))2](2+). Cyclic
      voltammetry reflects the qualitative structure change on the first, but not on
      the second oxidation of [Ni(QM)2], and spectroelectrochemistry reveals a
      pronounced dependence of the 800-900 nm absorption on the solvent and counterion.
      Reduction of the neutral form occurs in an electrochemically reversible step to
      yield an anion with an intense near-infrared absorption at 1345 nm (epsilon =
      10,400 M(-1)  cm(-1)) and a conventional g factor splitting for a largely metal
      based spin (S = 1/2), suggesting a [(QM(.-))Ni(II)(QM(2-))](-) configuration with
      a tetracoordinate metal atom with antiferromagnetic Ni(II)-(QM(.-)) interactions
      and symmetry-allowed ligand-to-ligand intervalence charge transfer (LLIVCT).
      Calculations are used to understand the Ni-S binding activity as induced by
      remote electron transfer at the iminobenzoquinone redox system.

PMID- 24665086
TI  - SNMMI comment on ASCO 2013 "Choosing wisely" recommendation on use of PET/CT in
      recurrent cancer surveillance.

PMID- 24665085
TI  - First-in-human molecular imaging of HER2 expression in breast cancer metastases
      using the 111In-ABY-025 affibody molecule.
AB  - The expression status of human epidermal growth factor receptor type 2 (HER2)
      predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a
      small reengineered Affibody molecule targeting a unique epitope of the HER2
      receptor, not occupied by current therapeutic agents. This study evaluated the
      distribution, safety, dosimetry, and efficacy of (111)In-ABY-025 for determining
      the HER2 status in metastatic breast cancer. METHODS: Seven patients with
      metastatic breast cancer and HER2-positive (n = 5) or -negative (n = 2) primary
      tumors received an intravenous injection of approximately 100 MUg (~ 140 MBq) of
      (111)In-ABY-025. Planar gamma-camera imaging was performed after 30 min, followed
      by SPECT/CT after 4, 24, and 48 h. Blood levels of radioactivity, antibodies,
      shed serum HER2, and toxicity markers were evaluated. Lesional HER2 status was
      verified by biopsies. The metastases were located by (18)F-FDG PET/CT 5 d before
      (111)In-ABY-025 imaging. RESULTS: Injection of (111)In-ABY-025 yielded a mean
      effective dose of 0.15 mSv/MBq and was safe, well tolerated, and without drug
      related adverse events. Fast blood clearance allowed high-contrast HER2 images
      within 4-24 h. No anti-ABY-025 antibodies were observed. When metastatic uptake
      at 24 h was normalized to uptake at 4 h, the ratio increased in HER2-positive
      metastases and decreased in negative ones (P < 0.05), with no overlap and
      confirmation by biopsies. In 1 patient, with HER2-positive primary tumor, (111)In
      ABY-025 imaging correctly suggested a HER2-negative status of the metastases. The
      highest normal-tissue uptake was in the kidneys, followed by the liver and
      spleen. CONCLUSION: (111)In-ABY-025 appears safe for use in humans and is a
      promising noninvasive tool for discriminating HER2 status in metastatic breast
      cancer, regardless of ongoing HER2-targeted antibody treatment.

PMID- 24665087
TI  - Glypican-3-targeted 89Zr PET imaging of hepatocellular carcinoma: where antibody
      imaging dares to tread.

PMID- 24665088
TI  - Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic
      Encephalomyelitis: An 11C-(R)-PK11195 PET Study.
AB  - Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease
      characterized by chronic, profound, disabling, and unexplained fatigue. Although
      it is hypothesized that brain inflammation is involved in the pathophysiology of
      CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME.
      Activation of microglia or astrocytes is related to neuroinflammation. (11)C-(R)
      (2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide ((11)C
      (R)-PK11195) is a ligand of PET for a translocator protein that is expressed by
      activated microglia or astrocytes. We used (11)C-(R)-PK11195 and PET to
      investigate the existence of neuroinflammation in CFS/ME patients. METHODS: Nine
      CFS/ME patients and 10 healthy controls underwent (11)C-(R)-PK11195 PET and
      completed questionnaires about fatigue, fatigue sensation, cognitive impairments,
      pain, and depression. To measure the density of translocator protein,
      nondisplaceable binding potential (BP(ND)) values were determined using linear
      graphical analysis with the cerebellum as a reference region. RESULTS: The BP(ND)
      values of (11)C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala,
      thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in
      healthy controls. In CFS/ME patients, the BP(ND) values of (11)C-(R)-PK11195 in
      the amygdala, thalamus, and midbrain positively correlated with cognitive
      impairment score, the BP(ND) values in the cingulate cortex and thalamus
      positively correlated with pain score, and the BP(ND) value in the hippocampus
      positively correlated with depression score. CONCLUSION: Neuroinflammation is
      present in widespread brain areas in CFS/ME patients and was associated with the
      severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME
      patients may be essential for understanding the core pathophysiology and for
      developing objective diagnostic criteria and effective medical treatments.

PMID- 24665089
TI  - Diagnostic and prognostic value of pretreatment SUV in 18F-FDG/PET in breast
      cancer: comparison with apparent diffusion coefficient from diffusion-weighted MR
      imaging.
AB  - In oncology, the apparent diffusion coefficient (ADC) measured by diffusion
      weighted MR imaging (DWI) and the standardized uptake value (SUV) from (18)F-FDG
      PET have similar clinical applications. The purpose of this study was to assess
      the correlation between the ADC and SUV and compare their potential in the
      diagnosis and prediction of prognosis in breast tumors. METHODS: Seventy-nine
      female patients (age range, 19-69 y; average, 49.1 y) with 83 pathologically
      proven breast tumors were recruited. The diagnoses consisted of 70 malignant
      breast tumors (65 cases of invasive ductal carcinoma, 1 of medullary carcinoma, 1
      of mucinous carcinoma, 1 of squamous cell carcinoma, and 2 of micropapillary
      carcinoma) and 13 benign breast tumors (4 cases of fibroadenoma, 4 of mastopathy,
      3 of adenosis with atypia, and 2 of benign phyllodes tumor). All patients
      underwent mammary gland MR imaging with DWI and (18)F-FDG PET within a 2-wk
      interval. The patients' ADCs and SUVs were measured within the tumor by DWI and
      (18)F-FDG PET, respectively. For the malignant tumors, we evaluated the
      relationships among ADC, SUV, histopathologic appearance, and long-term
      prognosis. RESULTS: A significant difference (P < 0.05) was observed in both
      parameters (ADC and SUV) between the benign and malignant breast tumors, and the
      difference was more significant when we introduced a new parameter, SUV/ADC.
      There was a weak inverse correlation between ADC and SUV (r = -0.36; P = 0.06)
      among the total tumors; however, this correlation was not significant within the
      group of malignant tumors. High SUV was found to correlate with larger tumor
      size, higher nuclear grade, and the triple-negative hormonal receptor profile.
      High ADC was revealed to be correlated with negative progesterone receptor and
      positive human epidermal growth factor receptor 2 profile. Higher SUVs also
      showed a correlation with poor prognosis. No correlation was seen between ADC and
      prognosis. CONCLUSION: Both SUV and ADC are helpful parameters in differentiating
      benign from malignant breast tumors. The use of SUV and ADC in combination may
      help in the diagnosis because of their inverse relationship. High preoperative
      SUV was associated with poor prognosis, but the contribution of ADC to prognosis
      prediction was small.

PMID- 24665090
TI  - The impact of predictive cues and visual working memory on dynamic oculomotor
      selection.
AB  - Strategic use of advanced information about search display properties can benefit
      covert attentional selection. However, little work has investigated this benefit
      on overt selection. The present study examined how cued information impacts
      oculomotor selection over time and the role played by individual differences in
      visual working memory (VWM) capacity in utilizing such cues. Participants
      searched for a specific orientation target in a saccade localization search task.
      Prior to each trial, additional information regarding secondary display features
      (color singleton identity) was either provided by a word cue or not. The cue
      increased accuracy performance from the earliest saccadic responses. VWM capacity
      was measured via a change-detection task and results showed that individuals' VWM
      capacity scores were associated with cue impact, whereby participants with higher
      capacity derived an increased cue performance benefit. These findings suggest
      that strategic use of cue information to select and reject salient singletons can
      develop very early following display presentation and is related to an
      individual's VWM capacity. This research indicates that stimulus-driven and goal
      directed processes are not simply additive in oculomotor selection, but instead
      exhibit a distinct and dynamic profile of interaction. 

PMID- 24665091
TI  - Modularity in the motion system: independent oculomotor and perceptual processing
      of brief moving stimuli.
AB  - In addition to motion perception per se, we utilize motion information for a wide
      range of brain functions. These varied functions place different demands on the
      visual system, and therefore a stimulus that provides useful information for one
      function may be inadequate for another. For example, the direction of motion of
      large high-contrast stimuli is difficult to discriminate perceptually, but other
      studies have shown that such stimuli are highly effective at eliciting
      directional oculomotor responses such as the ocular following response (OFR).
      Here, we investigated the degree of independence between perceptual and
      oculomotor processing by determining whether perceptually suppressed moving
      stimuli can nonetheless evoke reliable eye movements. We measured reflexively
      evoked tracking eye movements while observers discriminated the motion direction
      of large high-contrast stimuli. To quantify the discrimination ability of the
      oculomotor system, we used signal detection theory to generate associated
      oculometric functions. The results showed that oculomotor sensitivity to motion
      direction is not predicted by perceptual sensitivity to the same stimuli. In
      fact, in several cases oculomotor responses were more reliable than perceptual
      responses. Moreover, a trial-by-trial analysis indicated that, for stimuli tested
      in this study, oculomotor processing was statistically independent from
      perceptual processing. Evidently, perceptual and oculomotor responses reflect the
      activity of independent dissociable mechanisms despite operating on the same
      input. While results of this kind have traditionally been interpreted in the
      framework of perception versus action, we propose that these differences reflect
      a more general principle of modularity. 

PMID- 24665092
TI  - Defending Yarbus: eye movements reveal observers' task.
AB  - In a very influential yet anecdotal illustration, Yarbus suggested that human eye
      movement patterns are modulated top down by different task demands. While the
      hypothesis that it is possible to decode the observer's task from eye movements
      has received some support (e.g., Henderson, Shinkareva, Wang, Luke, & Olejarczyk,
      2013; Iqbal & Bailey, 2004), Greene, Liu, and Wolfe (2012) argued against it by
      reporting a failure. In this study, we perform a more systematic investigation of
      this problem, probing a larger number of experimental factors than previously.
      Our main goal is to determine the informativeness of eye movements for task and
      mental state decoding. We perform two experiments. In the first experiment, we
      reanalyze the data from a previous study by Greene et al. (2012) and contrary to
      their conclusion, we report that it is possible to decode the observer's task
      from aggregate eye-movement features slightly but significantly above chance,
      using a Boosting classifier (34.12% correct vs. 25% chance level; binomial test,
      p = 1.0722e - 04). In the second experiment, we repeat and extend Yarbus's
      original experiment by collecting eye movements of 21 observers viewing 15
      natural scenes (including Yarbus's scene) under Yarbus's seven questions. We show
      that task decoding is possible, also moderately but significantly above chance
      (24.21% vs. 14.29% chance-level; binomial test, p = 2.4535e - 06). We thus
      conclude that Yarbus's idea is supported by our data and continues to be an
      inspiration for future computational and experimental eye-movement research. From
      a broader perspective, we discuss techniques, features, limitations, societal and
      technological impacts, and future directions in task decoding from eye movements.

PMID- 24665094
TI  - Agonists binding nicotinic receptors elicit specific channel-opening patterns at
      alphagamma and alphadelta sites.
AB  - 'Embryonic' muscle-type nicotinic acetylcholine receptor channels (nAChRs) bind
      ligands at interfaces of alpha- and gamma- or delta-subunits. alphagamma and
      alphadelta sites differ in affinity, but their contributions to opening the
      channel have remained elusive. We compared high-resolution patch clamp currents
      evoked by epibatidine (Ebd), carbamylcholine (CCh) and acetylcholine (ACh). Ebd
      binds with 75-fold higher affinity at alphagamma than at alphadelta sites,
      whereas CCh and ACh prefer alphadelta sites. Similar short (tauO1), intermediate
      (tauO2) and long (tauO3) types of opening were observed with all three agonists.
      tauO2 openings were maximally prevalent at low Ebd concentrations, binding at
      alphagamma sites. By contrast, tauO1 openings appear to be generated at
      alphadelta sites. In addition, two types of burst appeared: short bursts of an
      average of 0.75 ms (tauB1) that should arise from the alphagamma site, and long
      bursts of 12-25 ms (tauB2) in duration arising from double liganded receptors.
      Limited by the temporal resolution, the closings within bursts were invariant at
      3 MUs. Corrected for missed closings, in the case of ACh the openings within long
      bursts lasted 170 MUs and those in short bursts about 30 MUs. Blocking alphadelta
      sites with alpha-conotoxin M1 (CTx) eliminated both tauO1 and tauB2 and left only
      tauO2 and the short tauB1 bursts, as expected. Furthermore we found
      desensitization when the receptors bound ACh only at the alphagamma site. When
      CTx was applied to 'embryonic' mouse endplates, monoquantal current rise times
      were increased, and amplitude and decay time constants were reduced, as expected.
      Thus the alphagamma and alphadelta sites of nAChRs elicit specific channel
      opening patterns.

PMID- 24665093
TI  - Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial
      endothelial dysfunction in mice.
AB  - Age-related arterial endothelial dysfunction, a key antecedent of the development
      of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide
      (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a
      major source and target of vascular oxidative stress when dysregulated.
      Mitochondrial dysregulation is associated with primary ageing, but its role in
      age-related endothelial dysfunction is unknown. Our aim was to determine the
      efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular
      endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent
      dilation (EDD) to increasing doses of acetylcholine was impaired by ~30% in old
      (~27 months) compared with young (~8 months) mice as a result of reduced NO
      bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking
      water) administration of MitoQ completely restored EDD in older mice by improving
      NO bioavailability. There were no effects of age or MitoQ on endothelium
      independent dilation to sodium nitroprusside. The improvements in endothelial
      function with MitoQ supplementation were associated with the normalization of age
      related increases in total and mitochondria-derived arterial superoxide
      production and oxidative stress (nitrotyrosine abundance), as well as with
      increases in markers of vascular mitochondrial health, including antioxidant
      status. MitoQ also reversed the age-related increase in endothelial
      susceptibility to acute mitochondrial damage (rotenone-induced impairment in
      EDD). Our results suggest that mitochondria-derived oxidative stress is an
      important mechanism underlying the development of endothelial dysfunction in
      primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a
      promising novel strategy for the preservation of vascular endothelial function
      with advancing age and the prevention of age-related CVD.

PMID- 24665095
TI  - Nucleus accumbens neuronal maturation differences in young rats bred for low
      versus high voluntary running behaviour.
AB  - We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34
      day-old rats selectively bred for low (LVR) versus high voluntary running (HVR)
      behaviours in rats that never ran (LVR(non-run) and HVR(non-run)), as well as in
      rats after 6 days of voluntary wheel running (LVR(run) and HVR(run)). In
      addition, the NAc transcriptome of wild-type Wistar rats was compared. The
      purpose of this transcriptomics approach was to generate testable hypotheses as
      to possible NAc features that may be contributing to running motivation
      differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses
      suggested that 'cell cycle'-related transcripts and the running-induced
      plasticity of dopamine-related transcripts were lower in LVR versus HVR rats.
      From these data, a hypothesis was generated that LVR rats might have less NAc
      neuron maturation than HVR rats. Follow-up immunohistochemistry in G9-10 LVR(non
      run) rats suggested that the LVR line inherently possessed fewer mature medium
      spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive)
      neurons (P < 0.001) than their G9-10 HVR counterparts. However, voluntary running
      wheel access in our G9-10 LVRs uniquely increased their Darpp-32-positive and Dcx
      positive neuron densities. In summary, NAc cellularity differences and/or the
      lack of running-induced plasticity in dopamine signalling-related transcripts may
      contribute to low voluntary running motivation in LVR rats.

PMID- 24665096
TI  - Limb position sense, proprioceptive drift and muscle thixotropy at the human
      elbow joint.
AB  - These experiments on the human forearm are based on the hypothesis that drift in
      the perceived position of a limb over time can be explained by receptor
      adaptation. Limb position sense was measured in 39 blindfolded subjects using a
      forearm-matching task. A property of muscle, its thixotropy, a contraction
      history-dependent passive stiffness, was exploited to place muscle receptors of
      elbow muscles in a defined state. After the arm had been held flexed and elbow
      flexors contracted, we observed time-dependent changes in the perceived position
      of the reference arm by an average of 2.8 degrees  in the direction of elbow
      flexion over 30 s (Experiment 1). The direction of the drift reversed after the
      arm had been extended and elbow extensors contracted, with a mean shift of 3.5
      degrees  over 30 s in the direction of elbow extension (Experiment 2). The time
      dependent changes could be abolished by conditioning elbow flexors and extensors
      in the reference arm at the test angle, although this led to large position
      errors during matching (+/-10 degrees ), depending on how the indicator arm had
      been conditioned (Experiments 3 and 4). When slack was introduced in the elbow
      muscles of both arms, by shortening muscles after the conditioning contraction,
      matching errors became small and there was no drift in position sense
      (Experiments 5 and 6). These experiments argue for a receptor-based mechanism for
      proprioceptive drift and suggest that to align the two forearms, the brain
      monitors the difference between the afferent signals from the two arms.

PMID- 24665097
TI  - Synaptic and paracrine mechanisms at carotid body arterial chemoreceptors.
AB  - Mammalian carotid bodies are the main peripheral arterial chemoreceptors,
      strategically located at the bifurcation of the common carotid artery. When
      stimulated these receptors initiate compensatory respiratory and cardiovascular
      reflexes to maintain homeostasis. Thus, in response to low oxygen (hypoxia) or
      increased CO2/H(+) (acid hypercapnia), chemoreceptor type I cells depolarize and
      release excitatory neurotransmitters, such as ATP, which stimulate postsynaptic
      P2X2/3 receptors on afferent nerve terminals. The afferent discharge is shaped by
      autocrine and paracrine mechanisms involving both excitatory and inhibitory
      neuromodulators such as adenosine, serotonin (5-HT), GABA and dopamine. Recent
      evidence suggests that paracrine activation of P2Y2 receptors on adjacent glia
      like type II cells may help boost the ATP signal via the opening of pannexin-1
      channels. The presence of an inhibitory efferent innervation, mediated by release
      of nitric oxide, provides additional control of the afferent discharge. The broad
      array of neuromodulators and their receptors appears to endow the carotid body
      with a remarkable plasticity, most apparent during natural and pathophysiological
      conditions associated with chronic sustained and intermittent hypoxia. 

PMID- 24665098
TI  - Synaptic communication and signal processing among sensory cells in taste buds.
AB  - Taste buds (sensory structures embedded in oral epithelium) show a remarkable
      diversity of transmitters synthesized and secreted locally. The known
      transmitters accumulate in a cell type selective manner, with 5-HT and
      noradrenaline being limited to presynaptic cells, GABA being synthesized in both
      presynaptic and glial-like cells, and acetylcholine and ATP used for signalling
      by receptor cells. Each of these transmitters participates in local negative or
      positive feedback circuits that target particular cell types. Overall, the role
      of ATP is the best elucidated. ATP serves as a principal afferent transmitter,
      and also is the key trigger for autocrine positive feedback and paracrine
      circuits that result in potentiation (via adenosine) or inhibition (via GABA or 5
      HT). While many of the cellular receptors and mechanisms for these circuits are
      known, their impact on sensory detection and perception remains to be elaborated
      in most instances. This brief review examines what is known, and some of the open
      questions and controversies surrounding the transmitters and circuits of the
      taste periphery. 

PMID- 24665099
TI  - It's a gut feeling: how the gut microbiota affects the state of mind.
AB  - Common human experience shows that stress and anxiety may modulate gut function.
      Such observations have been combined with an increasing evidence base that has
      culminated in the concept of the brain-gut axis. Nevertheless, it has not been
      until recently that the gut and its attendant components have been considered to
      influence higher cerebral function and behaviour per se. Moreover, the proposal
      that the gut and the bacteria contained therein (collectively referred to as the
      microbiota) can modulate mood and behaviours, has an increasing body of
      supporting evidence, albeit largely derived from animal studies. The gut
      microbiota is a dynamic and diverse ecosystem and forms a symbiotic relationship
      with the host. Herein we describe the components of the gut microbiota and
      mechanisms by which it can influence neural development, complex behaviours and
      nociception. Furthermore, we propose the novel concept of a 'state of gut' rather
      than a state of mind, particularly in relation to functional bowel disorders.
      Finally, we address the exciting possibility that the gut microbiota may offer a
      novel area of therapeutic intervention across a diverse array of both affective
      and gastrointestinal disorders. 

PMID- 24665100
TI  - Mapping the cellular electrophysiology of rat sympathetic preganglionic neurones
      to their roles in cardiorespiratory reflex integration: a whole cell recording
      study in situ.
AB  - Sympathetic preganglionic neurones (SPNs) convey sympathetic activity flowing
      from the CNS to the periphery to reach the target organs. Although previous in
      vivo and in vitro cell recording studies have explored their electrophysiological
      characteristics, it has not been possible to relate these characteristics to
      their roles in cardiorespiratory reflex integration. We used the working heart
      brainstem preparation to make whole cell patch clamp recordings from T3-4 SPNs (n
      = 98). These SPNs were classified by their distinct responses to activation of
      the peripheral chemoreflex, diving response and arterial baroreflex, allowing the
      discrimination of muscle vasoconstrictor-like (MVC(like), 39%) from cutaneous
      vasoconstrictor-like (CVC(like), 28%) SPNs. The MVC(like) SPNs have higher
      baseline firing frequencies (2.52 +/- 0.33 Hz vs. CVC(like) 1.34 +/- 0.17 Hz, P =
      0.007). The CVC(like) have longer after-hyperpolarisations (314 +/- 36 ms vs.
      MVC(like) 191 +/- 13 ms, P < 0.001) and lower input resistance (346 +/- 49 MOmega
      vs. MVC(like) 496 +/- 41 MOmega, P < 0.05). MVC(like) firing was respiratory
      modulated with peak discharge in the late inspiratory/early expiratory phase and
      this activity was generated by both a tonic and respiratory-modulated barrage of
      synaptic events that were blocked by intrathecal kynurenate. In contrast, the
      activity of CVC(like) SPNs was underpinned by rhythmical membrane potential
      oscillations suggestive of gap junctional coupling. Thus, we have related the
      intrinsic electrophysiological properties of two classes of SPNs in situ to their
      roles in cardiorespiratory reflex integration and have shown that they deploy
      different cellular mechanisms that are likely to influence how they integrate and
      shape the distinctive sympathetic outputs.

PMID- 24665101
TI  - Physiological underpinnings of irritable bowel syndrome: neurohormonal
      mechanisms.
AB  - The gastrointestinal tract is a vast neuroendocrine organ with extensive
      extrinsic and intrinsic neural circuits that interact to control its function.
      Circulating and paracrine hormones (amine and peptide) provide further control of
      secretory, absorptive, barrier, motor and sensory mechanisms that are essential
      to the digestion and assimilation of nutrients, and the transport and excretion
      of waste products. Specialized elements of the mucosa (including enteroendocrine
      cells, enterocytes and immune cells) and the microbiome interact with other
      intraluminal contents derived from the diet, and with endogenous chemicals that
      alter the gut's functions. The totality of these control mechanisms is often
      summarized as the brain-gut axis. In irritable bowel syndrome (IBS), which is the
      most common gastrointestinal disorder, there may be disturbances at one or more
      of these diverse control mechanisms. Patients present with abdominal pain in
      association with altered bowel function. This review documents advances in
      understanding the pathophysiological mechanisms in the brain-gut axis in patients
      with IBS. It is anticipated that identification of one or more disordered
      functions in clinical practice will usher in a renaissance in the management of
      IBS, leading to effective therapy tailored to the needs of the individual
      patient. 

PMID- 24665104
TI  - Triennial Growth Symposium: Vitamin D--establishing the basics to dispel the
      hype.

PMID- 24665102
TI  - Novel roles of gastrin.
AB  - The existence of the hormone gastrin in the distal stomach (antrum) has been
      known for almost 110 years, and the physiological function of this amidated
      peptide in regulating gastric acid secretion via the CCK2 receptor is now well
      established. In this brief review we consider important additional roles of
      gastrin, including regulation of genes encoding proteins such as plasminogen
      activator inhibitors and matrix metalloproteinases that have important actions on
      extracellular matrix remodelling. These actions are, at least in part, effected
      by paracrine signalling pathways and make important contributions to maintaining
      functional integrity of the gastric epithelium. Recent studies also provide
      support for the idea that gastrin, in concert with other hormones, could
      potentially contribute a post-prandial incretin effect. We also review recent
      developments in the biology of other gastrin gene products, including the
      precursor progastrin, which causes proliferation of the colonic epithelium and in
      certain circumstances may induce cancer formation. Glycine-extended biosynthetic
      processing intermediates also have proliferative effects in colonic mucosa and in
      some oesophageal cancer cell lines. Whether these additional gene products exert
      their effects through the CCK2 receptor or a separate entity is currently a
      matter of debate. 

PMID- 24665103
TI  - Activation of glycine receptors modulates spontaneous epileptiform activity in
      the immature rat hippocampus.
AB  - While the expression of glycine receptors in the immature hippocampus has been
      shown, no information about the role of glycine receptors in controlling the
      excitability in the immature CNS is available. Therefore, we examined the effect
      of glycinergic agonists and antagonists in the CA3 region of an intact
      corticohippocampal preparation of the immature (postnatal days 4-7) rat using
      field potential recordings. Bath application of 100 MUM taurine or 10 MUM glycine
      enhanced the occurrence of recurrent epileptiform activity induced by 20 MUM 4
      aminopyridine in low Mg(2+) solution. This proconvulsive effect was prevented by
      3 MUM strychnine or after incubation with the loop diuretic bumetanide (10 MUM),
      suggesting that it required glycine receptors and an active NKCC1-dependent Cl(-)
      accumulation. Application of higher doses of taurine (>= 1 mM) or glycine (100
      MUM) attenuated recurrent epileptiform discharges. The anticonvulsive effect of
      taurine was also observed in the presence of the GABAA receptor antagonist
      gabazine and was attenuated by strychnine, suggesting that it was partially
      mediated by glycine receptors. Bath application of the glycinergic antagonist
      strychnine (0.3 MUM) induced epileptiform discharges. We conclude from these
      results that in the immature hippocampus, activation of glycine receptors can
      mediate both pro- and anticonvulsive effects, but that a persistent activation of
      glycine receptors is required to suppress epileptiform activity. In summary, our
      study elucidated the important role of glycine receptors in the control of
      neuronal excitability in the immature hippocampus.

PMID- 24665105
TI  - Triennial Growth Symposium--Novel roles for vitamin D in animal immunity and
      health.
AB  - Recent years have seen significant advances in the generation, validation, and
      implementation of nutritional supplements for food production animals.
      Examination of their impact on animal performance and health requires
      collaboration among animal scientists, nutritionists, biochemists, immunologists,
      veterinarians, and others. Each provides a unique perspective on the mechanisms
      of action, short and long-term impacts, and most effective strategies for
      implementation into continuously evolving industrial practices. In this review we
      provide a comparative immunology perspective on the impact of vitamin D on animal
      performance and health, describe the differential contributions of vitamin D3 and
      of a commercial hydroxylated version of vitamin D3, 25-hydroxyvitamin D3
      (25(OH)D3 or HyD) to swine immunity, and highlight recent advances in the
      technologies that can be used to dissect the cellular and molecular mechanisms
      that impact production animal immunity and health. Among others, we pay
      particular attention to how these novel approaches help decrease the variability
      often observed in immune-associated datasets. From a practical perspective, this
      is critical for evaluation of in vivo effects for this nutritional supplement as
      small but meaningful changes to specific immune responses are typical under
      normal physiological conditions. Furthermore, as the range of reagents and
      technologies expands for comparative animal models, it is imperative that
      continued efforts are placed on the capacity to compare results across different
      experimental platforms. 

PMID- 24665106
TI  - Does diverse grazing behavior of suckler cows have an impact on predicted methane
      emissions?
AB  - A modeling study based on a dataset from a large-scale grazing study was used to
      identify the potential impact of grazing behavior and performance of diverse cow
      genotypes on predicted methane (CH4) emissions. Lactating cows grazing extensive
      seminatural grassland and heath vegetation were monitored with Global Positioning
      System collars and activity sensors. The diet selected by cows of 3 different
      genotypes, Aberdeen Angus cross Limousin (AxL), Charolais (CHA), and Luing (LUI),
      was simulated by matching their locations during active periods with hill
      vegetation maps. Measured performance and activity were used to predict energy
      requirements, DMI, and CH4 output. The cumulative effect of actual performance,
      diet selection, and actual physical activity on potential CH4 output and yield
      was estimated. Sensitivity analyses were performed for the digestibility of
      intake, energy cost of activity, proportion of milk consumed by calves, and
      reproductive efficiency. Although with a better performance (P < 0.05), LUI
      required less total energy than the other genotypes (P < 0.001) as the other 2
      spent more energy for maintenance (P < 0.001) and activity (P < 0.001). By
      selecting a better quality diet (P < 0.03), estimated CH4 of CHA cow-calf pairs
      was lower than AxL (P = 0.001) and slightly lower than LUI (P = 0.08). Energy
      lost as CH4 was 0.17 and 0.58% lower for LUI than AxL and CHA (P < 0.002). This
      study suggests for the first time that measured activity has a major impact on
      estimated CH4 outputs. A 15% difference of the cow-calf pair CH4 was estimated
      when using different coefficients to convert actual activity into energy.
      Predicted CH4 was highly sensitive to small changes in diet quality, suggesting
      the relative importance of diet selection on heterogeneous rangelands. Extending
      these results to a farm systems scale, CH4 outputs were also highly sensitive to
      reductions in weaning rates, illustrating the impact on CH4 at the farm-system
      level of using poorly adapted genotypes on habitats where their performances may
      be compromised. This paper demonstrates that variations in grazing behavior and
      grazing choice have a potentially large impact on CH4 emissions, illustrating the
      importance of including these factors in calculating realistic national and
      global estimates. 

PMID- 24665108
TI  - How to incorporate the dose-rate effect into evaluation of cancer risk for
      radiation protection.

PMID- 24665110
TI  - Advanced REACH Tool: a Bayesian model for occupational exposure assessment.
AB  - This paper describes a Bayesian model for the assessment of inhalation exposures
      in an occupational setting; the methodology underpins a freely available web
      based application for exposure assessment, the Advanced REACH Tool (ART). The ART
      is a higher tier exposure tool that combines disparate sources of information
      within a Bayesian statistical framework. The information is obtained from expert
      knowledge expressed in a calibrated mechanistic model of exposure assessment,
      data on inter- and intra-individual variability in exposures from the literature,
      and context-specific exposure measurements. The ART provides central estimates
      and credible intervals for different percentiles of the exposure distribution,
      for full-shift and long-term average exposures. The ART can produce exposure
      estimates in the absence of measurements, but the precision of the estimates
      improves as more data become available. The methodology presented in this paper
      is able to utilize partially analogous data, a novel approach designed to make
      efficient use of a sparsely populated measurement database although some
      additional research is still required before practical implementation. The
      methodology is demonstrated using two worked examples: an exposure to copper
      pyrithione in the spraying of antifouling paints and an exposure to ethyl acetate
      in shoe repair. 

PMID- 24665109
TI  - Arabidopsis PECTIN METHYLESTERASE17 is co-expressed with and processed by SBT3.5,
      a subtilisin-like serine protease.
AB  - BACKGROUND AND AIMS: In Arabidopsis thaliana, the degree of methylesterification
      (DM) of homogalacturonans (HGs), the main pectic constituent of the cell wall,
      can be modified by pectin methylesterases (PMEs). In all organisms, two types of
      protein structure have been reported for PMEs: group 1 and group 2. In group 2
      PMEs, the active part (PME domain, Pfam01095) is preceded by an N-terminal
      extension (PRO part), which shows similarities to PME inhibitors (PMEI domain,
      Pfam04043). This PRO part mediates retention of unprocessed group 2 PMEs in the
      Golgi apparatus, thus regulating PME activity through a post-translational
      mechanism. This study investigated the roles of a subtilisin-type serine protease
      (SBT) in the processing of a PME isoform. METHODS: Using a combination of
      functional genomics, biochemistry and proteomic approaches, the role of a
      specific SBT in the processing of a group 2 PME was assessed together with its
      consequences for plant development. KEY RESULTS: A group 2 PME, AtPME17
      (At2g45220), was identified, which was highly co-expressed, both spatially and
      temporally, with AtSBT3.5 (At1g32940), a subtilisin-type serine protease
      (subtilase, SBT), during root development. PME activity was modified in roots of
      knockout mutants for both proteins with consequent effects on root growth. This
      suggested a role for SBT3.5 in the processing of PME17 in planta. Using transient
      expression in Nicotiana benthamiana, it was indeed shown that SBT3.5 can process
      PME17 at a specific single processing motif, releasing a mature isoform in the
      apoplasm. CONCLUSIONS: By revealing the potential role of SBT3.5 in the
      processing of PME17, this study brings new evidence of the complexity of the
      regulation of PMEs in plants, and highlights the need for identifying specific
      PME-SBT pairs.

PMID- 24665111
TI  - Computational fluid dynamics investigation of human aspiration in low velocity
      air: orientation effects on nose-breathing simulations.
AB  - An understanding of how particles are inhaled into the human nose is important
      for developing samplers that measure biologically relevant estimates of exposure
      in the workplace. While previous computational mouth-breathing investigations of
      particle aspiration have been conducted in slow moving air, nose breathing still
      required exploration. Computational fluid dynamics was used to estimate nasal
      aspiration efficiency for an inhaling humanoid form in low velocity wind speeds
      (0.1-0.4 m s(-1)). Breathing was simplified as continuous inhalation through the
      nose. Fluid flow and particle trajectories were simulated over seven discrete
      orientations relative to the oncoming wind (0, 15, 30, 60, 90, 135, 180 degrees
      ). Sensitivities of the model simplification and methods were assessed,
      particularly the placement of the recessed nostril surface and the size of the
      nose. Simulations identified higher aspiration (13% on average) when compared to
      published experimental wind tunnel data. Significant differences in aspiration
      were identified between nose geometry, with the smaller nose aspirating an
      average of 8.6% more than the larger nose. Differences in fluid flow solution
      methods accounted for 2% average differences, on the order of methodological
      uncertainty. Similar trends to mouth-breathing simulations were observed
      including increasing aspiration efficiency with decreasing freestream velocity
      and decreasing aspiration with increasing rotation away from the oncoming wind.
      These models indicate nasal aspiration in slow moving air occurs only for
      particles <100 um. 

PMID- 24665112
TI  - Positron emission tomography assessment of large vessel inflammation in patients
      with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case
      control study.
AB  - BACKGROUND: Positron emission tomography (PET) scan is emerging as a promising
      imaging technique to detect large-vessel inflammation in giant cell arteritis
      (GCA). However, the lack of a standardised definition of arteritis based on
      (18)fluorodeoxyglucose (FDG) uptake is an important limitation to the use of PET
      scan for diagnostic purposes. OBJECTIVE: To prospectively assess the intensity
      and distribution of FDG uptake at different vascular territories in patients with
      newly diagnosed GCA compared with controls. METHODS: 32 consecutive, biopsy
      proven, GCA patients treated with glucocorticoids for <=3 days were included. The
      control group consisted of 20 individuals, who underwent PET/CT for cancer
      staging. Maximal standardised uptake value (SUVm) was calculated at four aortic
      segments, supraaortic branches and iliac-femoral territory. Sensitivity and
      specificity was calculated by receiver-operator characteristic curves (ROC)
      analysis. RESULTS: Mean SUVm was significantly higher in patients than in
      controls in all vessels explored and correlated with acute-phase reactants and
      serum IL-6. Mean of the SUVm at all the vascular territories had an area under
      the curve (AUC) of 0.830, and a cut-off of 1.89 yielded a sensitivity of 80% and
      a specificity of 79% for GCA diagnosis. There were no significant differences in
      AUC among the vascular beds examined. CONCLUSIONS: FDG uptake by large vessels
      has a substantial sensitivity and specificity for GCA diagnosis.

PMID- 24665113
TI  - Reference intervals of spinal mobility measures in normal individuals: the
      MOBILITY study.
AB  - OBJECTIVES: To establish reference intervals (RIs) for spinal mobility measures
      as recommended for patients with axial spondyloarthritis, and to determine the
      effect of age, height and gender on spinal mobility, in normal individuals.
      METHODS: A cross-sectional study (MOBILITY) was conducted among normal
      individuals aged 20-69 years. Recruitment was stratified by gender, age (10-year
      categories) and height (10 cm categories). Eleven spinal mobility measures were
      assessed. Age specific RIs and percentiles were derived for each measure.
      RESULTS: 393 volunteers were included. All spinal mobility measures decreased
      with increasing age. Therefore, age specific RIs were developed. The 95% RIs
      (2.5th and 97.5th percentiles), as well as the 5th, 10th, 25th, 50th, 75th and
      90th percentiles for each spinal mobility measure and different ages are
      presented. Mobility percentile curves were also plotted for each of the measures.
      For instance, the 95% RI for lateral spinal flexion was 16.2-28.0 cm for a 25
      year-old subject, 13.2-25.0 cm for a 45-year-old subject and 10.1-21.9 cm for a
      65-year-old subject. After adjustment for age, there was no need for gender
      specific RIs, while RIs of some measures are height-adjusted. CONCLUSIONS: Age
      specific RIs and percentiles were derived for each of the spinal mobility
      measures for normal individuals. These may guide clinicians when assessing the
      mobility of patients with axial spondyloarthritis. The RIs may serve as cut-off
      levels for 'normal' versus 'abnormal', whereas the mobility percentile curves may
      be used to assess the level of mobility of patients with axial spondyloarthritis.

PMID- 24665114
TI  - A key role for Fut1-regulated angiogenesis and ICAM-1 expression in K/BxN
      arthritis.
AB  - OBJECTIVES: Angiogenesis contributes to the pathogenesis of rheumatoid arthritis.
      Fucosyltransferases (Futs) are involved in angiogenesis and tumour growth. Here,
      we examined the role of Fut1 in angiogenesis and K/BxN serum transfer arthritis.
      METHODS: We examined Fut1 expression in human dermal microvascular endothelial
      cells (HMVECs) by quantitative PCR. We performed a number of angiogenesis assays
      to determine the role of Fut1 using HMVECs, Fut1 null (Fut1(-/-)), and wild type
      (wt) endothelial cells (ECs) and mice. K/BxN serum transfer arthritis was
      performed to determine the contribution of Fut1-mediated angiogenesis in Fut1(-/
      ) and wt mice. A static adhesion assay was implemented with RAW264.7 (mouse
      macrophage cell line) and mouse ECs. Quantitative PCR, immunofluorescence and
      flow cytometry were performed with Fut1(-/-) and wt ECs for adhesion molecule
      expression. RESULTS: Tumour necrosis factor-alpha induced Fut1 mRNA and protein
      expression in HMVECs. HMVECs transfected with Fut1 antisense oligodeoxynucleotide
      and Fut1(-/-) ECs formed significantly fewer tubes on Matrigel. Fut1(-/-) mice
      had reduced angiogenesis in Matrigel plug and sponge granuloma angiogenesis
      assays compared with wt mice. Fut1(-/-) mice were resistant to K/BxN serum
      transfer arthritis and had decreased angiogenesis and leucocyte ingress into
      inflamed joints. Adhesion of RAW264.7 cells to wt mouse ECs was significantly
      reduced when Fut1 was lacking. Fut1(-/-) ECs had decreased intercellular adhesion
      molecule-1 (ICAM-1) expression at mRNA and protein levels compared with wt ECs.
      ICAM-1 was also decreased in Fut1(-/-) arthritic ankle cryosections compared with
      wt ankles. CONCLUSIONS: Fut1 plays an important role in regulating angiogenesis
      and ICAM-1 expression in inflammatory arthritis.

PMID- 24665116
TI  - The global burden of low back pain: estimates from the Global Burden of Disease
      2010 study.
AB  - OBJECTIVE: To estimate the global burden of low back pain (LBP). METHODS: LBP was
      defined as pain in the area on the posterior aspect of the body from the lower
      margin of the twelfth ribs to the lower glutaeal folds with or without pain
      referred into one or both lower limbs that lasts for at least one day. Systematic
      reviews were performed of the prevalence, incidence, remission, duration, and
      mortality risk of LBP. Four levels of severity were identified for LBP with and
      without leg pain, each with their own disability weights. The disability weights
      were applied to prevalence values to derive the overall disability of LBP
      expressed as years lived with disability (YLDs). As there is no mortality from
      LBP, YLDs are the same as disability-adjusted life years (DALYs). RESULTS: Out of
      all 291 conditions studied in the Global Burden of Disease 2010 Study, LBP ranked
      highest in terms of disability (YLDs), and sixth in terms of overall burden
      (DALYs). The global point prevalence of LBP was 9.4% (95% CI 9.0 to 9.8). DALYs
      increased from 58.2 million (M) (95% CI 39.9M to 78.1M) in 1990 to 83.0M (95% CI
      56.6M to 111.9M) in 2010. Prevalence and burden increased with age. CONCLUSIONS:
      LBP causes more global disability than any other condition. With the ageing
      population, there is an urgent need for further research to better understand LBP
      across different settings.

PMID- 24665115
TI  - The autoimmune-associated genetic variant PTPN22 R620W enhances neutrophil
      activation and function in patients with rheumatoid arthritis and healthy
      individuals.
AB  - OBJECTIVES: A genetic variant of the leukocyte phosphatase PTPN22 (R620W) is
      strongly associated with autoimmune diseases including rheumatoid arthritis (RA).
      Functional studies on the variant have focussed on lymphocytes, but it is most
      highly expressed in neutrophils. We have investigated the effects of the variant
      on neutrophil function in health and in patients with RA. METHODS: Healthy
      individuals and patients with RA were genotyped for PTPN22 (R620W) and
      neutrophils isolated from peripheral blood. Neutrophil adhesion and migration
      across inflamed endothelium were measured. Calcium (Ca(2+)) release and reactive
      oxygen species (ROS) production in response to fMLP stimulation were also
      assessed. RESULTS: Expression of R620W enhanced neutrophil migration through
      cytokine activated endothelium (non-R620W=24%, R620W=45% migrating cells,
      p<0.001). Following fMLP stimulation, neutrophils that were heterozygous and
      homozygous for R620W released significantly more Ca(2+) when compared to non
      R620W neutrophils, in healthy individuals and patients with RA. fMLP stimulation,
      after TNF-alpha priming, provoked more ROS from neutrophils heterozygous for
      R620W in patients with RA (non-R620W vs R620W=~1.75-fold increase) and healthy
      individuals (non-R620W vs R620W=fourfold increase) and this increase was
      statistically significant in healthy individuals (p<0.001) but not in patients
      with RA (p<0.25). CONCLUSIONS: Expression of PTPN22 (R620W) enhanced neutrophil
      effector functions in health and RA, with migration, Ca(2+) release and
      production of ROS increased. Neutrophils are found in large numbers in the RA
      joint, and this hyperactivity of R620W cells may directly contribute to the joint
      damage, as well as to the initiation and perpetuation of the chronic immune
      mediated inflammatory processes driving the disease.

PMID- 24665117
TI  - The global burden of occupationally related low back pain: estimates from the
      Global Burden of Disease 2010 study.
AB  - OBJECTIVES: The study was part of the Global Burden of Disease 2010 study and
      aimed to quantify the burden arising from low back pain (LBP) due to occupational
      exposure to ergonomic risk factors. METHODS: Exposure prevalence was based on
      occupation distribution; estimates of relative risk came from a meta-analysis of
      relevant published literature. The work-related burden was estimated as
      disability-adjusted life years (DALYs). Estimates were made for each of 21 world
      regions and 187 countries, separately for 1990 and 2010 using consistent methods.
      RESULTS: Worldwide, LBP arising from ergonomic exposures at work was estimated to
      cause 21.7 million DALYs in 2010. The overall population attributable fraction
      was 26%, varying considerably with age, sex and region. 62% of LBP DALYs were in
      males-the largest numbers were in persons aged 35-55 years. The highest relative
      risk (3.7) was in the agricultural sector. The largest number of DALYs occurred
      in East Asia and South Asia, but on a per capita basis the biggest burden was in
      Oceania. There was a 22% increase in overall LBP DALYs arising from occupational
      exposures between 1990 and 2010 due to population growth; rates dropped by 14%
      over the same period. CONCLUSIONS: LBP arising from ergonomic exposures at work
      is an important cause of disability. There is a need for improved information on
      exposure distributions and relative risks, particularly in developing countries.

PMID- 24665118
TI  - Allopurinol initiation and all-cause mortality in the general population.
AB  - BACKGROUND: Allopurinol is the most commonly used urate-lowering therapy, with
      rare but potentially fatal adverse effects. However, its impact on overall
      mortality remains largely unknown. In this study, we evaluated the impact of
      allopurinol initiation on the risk of mortality among individuals with
      hyperuricaemia and among those with gout in the general population. METHODS: We
      conducted an incident user cohort study with propensity score matching using a UK
      general population database. The study population included individuals aged >=40
      years who had a record of hyperuricaemia (serum urate level >357 MUmol/L for
      women and >416 MUmol/L for men) between January 2000 and May 2010. To closely
      account for potential confounders of allopurinol use and risk of death, we
      constructed propensity score matched cohorts of allopurinol initiators and
      comparators (non-initiators) within 6-month cohort accrual blocks. RESULTS: Of
      5927 allopurinol initiators and 5927 matched comparators, 654 and 718,
      respectively, died during the follow-up (mean=2.9 years). The baseline
      characteristics were well balanced in the two groups, including the prevalence of
      gout in each group (84%). Allopurinol initiation was associated with a lower risk
      of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited
      the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to
      0.92). CONCLUSIONS: In this general population study, allopurinol initiation was
      associated with a modestly reduced risk of death in patients with hyperuricaemia
      and patients with gout. The overall benefit of allopurinol on survival may
      outweigh the impact of rare serious adverse effects.

PMID- 24665119
TI  - Recent highlights of ATVB: aneurysms.

PMID- 24665120
TI  - Myeloperoxidase-mediated dysfunctional high-density lipoprotein.

PMID- 24665121
TI  - Skin autofluorescence, 5-year mortality, and cardiovascular events in peripheral
      arterial disease: all that glitters is surely not gold.

PMID- 24665122
TI  - The ABC of Thrombopoiesis.

PMID- 24665123
TI  - Risk of ischemic stroke and decreased serum bilirubin levels: is there a causal
      link?

PMID- 24665124
TI  - 2013 Russell Ross memorial lecture in vascular biology: cellular and molecular
      mechanisms of diabetes mellitus-accelerated atherosclerosis.
AB  - Adults with diabetes mellitus are much more likely to have cardiovascular disease
      than those without diabetes mellitus. Genetically engineered mouse models have
      started to provide important insight into the mechanisms whereby diabetes
      mellitus promotes atherosclerosis. Such models have demonstrated that diabetes
      mellitus promotes formation of atherosclerotic lesions, progression of lesions
      into advanced hemorrhaged lesions, and that it prevents lesion regression. The
      proatherosclerotic effects of diabetes mellitus are driven in part by the altered
      function of myeloid cells. The protein S100A9 and the receptor for advanced
      glycation end-products are important modulators of the effect of diabetes
      mellitus on myelopoiesis, which might promote monocyte accumulation in lesions.
      Furthermore, myeloid cell expression of the enzyme acyl-CoA synthetase 1 (ACSL1),
      which converts long-chain fatty acids into their acyl-CoA derivatives, has
      emerged as causal to diabetes mellitus-induced lesion initiation. The protective
      effects of myeloid ACSL1-deficiency in diabetic mice, but not in nondiabetic
      mice, indicate that myeloid cells are activated by diabetes mellitus through
      mechanisms that play minor roles in the absence of diabetes mellitus. The roles
      of reactive oxygen species and insulin resistance in diabetes mellitus
      accelerated atherosclerosis are also discussed, primarily in relation to
      endothelial cells. Translational studies addressing whether the mechanisms
      identified in mouse models are equally important in humans with diabetes mellitus
      will be paramount. 

PMID- 24665125
TI  - Inflammatory, metabolic, and genetic mechanisms of vascular calcification.
AB  - This review centers on updating the active research area of vascular
      calcification. This pathology underlies substantial cardiovascular morbidity and
      mortality, through adverse mechanical effects on vascular compliance, vasomotion,
      and, most likely, plaque stability. Biomineralization is a complex, regulated
      process occurring widely throughout nature. Decades ago, its presence in the
      vasculature was considered a mere curiosity and an unregulated, dystrophic
      process that does not involve biological mechanisms. Although it remains
      controversial whether the process has any adaptive value or past evolutionary
      advantage, substantial advances have been made in understanding the biological
      mechanisms driving the process. Different types of calcific vasculopathy, such as
      inflammatory versus metabolic, have parallel mechanisms in skeletal bone
      calcification, such as intramembranous and endochondral ossification. Recent work
      has identified important regulatory roles for inflammation, oxidized lipids,
      elastin, alkaline phosphatase, osteoprogenitor cells, matrix gamma
      carboxyglutamic acid protein, transglutaminase, osteoclastic regulatory factors,
      phosphate regulatory hormones and receptors, apoptosis, prelamin A, autophagy,
      and microvesicles or microparticles similar to the matrix vesicles of skeletal
      bone. Recent work has uncovered fascinating interactions between matrix gamma
      carboxyglutamic acid protein, vitamin K, warfarin, and transport proteins. And,
      lastly, recent breakthroughs in inherited forms of calcific vasculopathy have
      identified the genes responsible as well as an unexpected overlap of phenotypes.
      Until recently, vascular calcification was considered a purely degenerative,
      unregulated process. Since then, investigative groups around the world have
      identified a wide range of causative mechanisms and regulatory pathways, and some
      of the recent developments are highlighted in this review. 

PMID- 24665128
TI  - Drosophila epigenome reorganization during oocyte differentiation and early
      embryogenesis.
AB  - In sexually reproducing organisms, propagation of the species relies on
      specialized haploid cells (gametes) produced by germ cells. During their
      development in the adult germline, the female and male gametes undergo a complex
      differentiation process that requires transcriptional regulation and chromatin
      reorganization. After fertilization, the gametes then go through extensive
      epigenetic reprogramming, which resets the cells to a totipotent state essential
      for the development of the embryo. Several histone modifications characterize
      distinct developmental stages of gamete formation and early embryonic
      development, but it is unknown whether these modifications have any physiological
      role. Furthermore, accumulating evidence suggests that environmentally induced
      chromatin changes can be inherited, yet the mechanisms underlying zygotic
      inheritance of the gamete epigenome remain unclear. This review gives a brief
      overview of the mechanisms of transgenerational epigenetic inheritance and
      examines the function of epigenetics during oogenesis and early embryogenesis
      with a focus on histone posttranslational modifications. 

PMID- 24665126
TI  - Conserved transcriptional regulatory mechanisms in aortic valve development and
      disease.
AB  - There is increasing evidence for activation of developmental transcriptional
      regulatory pathways in heart valve disease. Here, we review molecular regulatory
      mechanisms involved in heart valve progenitor development, leaflet morphogenesis,
      and extracellular matrix organization that also are active in diseased aortic
      valves. These include regulators of endothelial-to-mesenchymal transitions, such
      as the Notch pathway effector RBPJ, and the valve progenitor markers Twist1,
      Msx1/2, and Sox9. Little is known of the potential reparative or pathological
      functions of these developmental mechanisms in adult aortic valves, but it is
      tempting to speculate that valve progenitor cells could contribute to repair in
      the context of disease. Likewise, loss of either RBPJ or Sox9 leads to aortic
      valve calcification in mice, supporting a potential therapeutic role in
      prevention of disease. During aortic valve calcification, transcriptional
      regulators of osteogenic development are activated in addition to valve
      progenitor regulatory programs. Specifically, the transcription factor Runx2 and
      its downstream target genes are induced in calcified valves. Runx2 and osteogenic
      genes also are induced with vascular calcification, but activation of valve
      progenitor markers and the cellular context of expression are likely to be
      different for valve and vascular calcification. Additional research is necessary
      to determine whether developmental mechanisms contribute to valve repair or
      whether these pathways can be harnessed for new treatments of heart valve
      disease. 

PMID- 24665130
TI  - Improving MEME via a two-tiered significance analysis.
AB  - MOTIVATION: With over 9000 unique users recorded in the first half of 2013, MEME
      is one of the most popular motif-finding tools available. Reliable estimates of
      the statistical significance of motifs can greatly increase the usefulness of any
      motif finder. By analogy, it is difficult to imagine evaluating a BLAST result
      without its accompanying E-value. Currently MEME evaluates its EM-generated
      candidate motifs using an extension of BLAST's E-value to the motif-finding
      context. Although we previously indicated the drawbacks of MEME's current
      significance evaluation, we did not offer a practical substitute suited for its
      needs, especially because MEME also relies on the E-value internally to rank
      competing candidate motifs. RESULTS: Here we offer a two-tiered significance
      analysis that can replace the E-value in selecting the best candidate motif and
      in evaluating its overall statistical significance. We show that our new approach
      could substantially improve MEME's motif-finding performance and would also
      provide the user with a reliable significance analysis. In addition, for large
      input sets, our new approach is in fact faster than the currently implemented E
      value analysis.

PMID- 24665129
TI  - Assessing multivariate gene-metabolome associations with rare variants using
      Bayesian reduced rank regression.
AB  - MOTIVATION: A typical genome-wide association study searches for associations
      between single nucleotide polymorphisms (SNPs) and a univariate phenotype.
      However, there is a growing interest to investigate associations between genomics
      data and multivariate phenotypes, for example, in gene expression or metabolomics
      studies. A common approach is to perform a univariate test between each genotype
      phenotype pair, and then to apply a stringent significance cutoff to account for
      the large number of tests performed. However, this approach has limited ability
      to uncover dependencies involving multiple variables. Another trend in the
      current genetics is the investigation of the impact of rare variants on the
      phenotype, where the standard methods often fail owing to lack of power when the
      minor allele is present in only a limited number of individuals. RESULTS: We
      propose a new statistical approach based on Bayesian reduced rank regression to
      assess the impact of multiple SNPs on a high-dimensional phenotype. Because of
      the method's ability to combine information over multiple SNPs and phenotypes, it
      is particularly suitable for detecting associations involving rare variants. We
      demonstrate the potential of our method and compare it with alternatives using
      the Northern Finland Birth Cohort with 4702 individuals, for whom genome-wide SNP
      data along with lipoprotein profiles comprising 74 traits are available. We
      discovered two genes (XRCC4 and MTHFD2L) without previously reported
      associations, which replicated in a combined analysis of two additional cohorts:
      2390 individuals from the Cardiovascular Risk in Young Finns study and 3659
      individuals from the FINRISK study. AVAILABILITY AND IMPLEMENTATION: R-code
      freely available for download at
      http://users.ics.aalto.fi/pemartti/gene_metabolome/.

PMID- 24665131
TI  - Prediction of individualized therapeutic vulnerabilities in cancer from genomic
      profiles.
AB  - MOTIVATION: Somatic homozygous deletions of chromosomal regions in cancer, while
      not necessarily oncogenic, may lead to therapeutic vulnerabilities specific to
      cancer cells compared with normal cells. A recently reported example is the loss
      of one of the two isoenzymes in glioblastoma cancer cells such that the use of a
      specific inhibitor selectively inhibited growth of the cancer cells, which had
      become fully dependent on the second isoenzyme. We have now made use of the
      unprecedented conjunction of large-scale cancer genomics profiling of tumor
      samples in The Cancer Genome Atlas (TCGA) and of tumor-derived cell lines in the
      Cancer Cell Line Encyclopedia, as well as the availability of integrated pathway
      information systems, such as Pathway Commons, to systematically search for a
      comprehensive set of such epistatic vulnerabilities. RESULTS: Based on homozygous
      deletions affecting metabolic enzymes in 16 TCGA cancer studies and 972 cancer
      cell lines, we identified 4104 candidate metabolic vulnerabilities present in
      1019 tumor samples and 482 cell lines. Up to 44% of these vulnerabilities can be
      targeted with at least one Food and Drug Administration-approved drug. We suggest
      focused experiments to test these vulnerabilities and clinical trials based on
      personalized genomic profiles of those that pass preclinical filters. We conclude
      that genomic profiling will in the future provide a promising basis for network
      pharmacology of epistatic vulnerabilities as a promising therapeutic strategy.
      AVAILABILITY AND IMPLEMENTATION: A web-based tool for exploring all
      vulnerabilities and their details is available at
      http://cbio.mskcc.org/cancergenomics/statius/ along with supplemental data files.

PMID- 24665133
TI  - Microvascular oxygen consumption during sickle cell pain crisis.
AB  - Sickle cell disease is an inherited blood disorder characterized by chronic
      hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs
      when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in
      the microvasculature, a process dependent on the concentration of hemoglobin S
      and the rate of deoxygenation, among other factors. We measured oxygen
      consumption in the thenar eminence during brachial artery occlusion in sickle
      cell patients and healthy individuals. Microvascular oxygen consumption was
      greater in sickle cell patients than in healthy individuals (median
      [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94]
      -DeltaHbO2/min, P < .05) and was elevated further during acute pain crisis
      (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -DeltaHbO2/min, P <
      .05). Increased microvascular oxygen consumption during pain crisis could affect
      the local oxygen saturation of hemoglobin when oxygen delivery is limiting.
      Identifying the mechanisms of elevated oxygen consumption during pain crisis
      might lead to the development of new therapeutic interventions. This trial was
      registered at www.clinicaltrials.gov as #NCT01568710. 

PMID- 24665132
TI  - Prevalence and causes of vision loss in high-income countries and in Eastern and
      Central Europe: 1990-2010.
AB  - BACKGROUND: To assess prevalence and causes of blindness and vision impairment in
      high-income regions and in Central/Eastern Europe in 1990 and 2010. METHODS:
      Based on a systematic review of medical literature, prevalence of moderate and
      severe vision impairment (MSVI; presenting visual acuity <6/18 but >=3/60 in the
      better eye) and blindness (presenting visual acuity <3/60) was estimated for 1990
      and 2010. RESULTS: Age-standardised prevalence of blindness and MSVI decreased
      from 0.2% to 0.1% (3.314 million to 2.736 million people) and from 1.6% to 1.0%
      (25.362 million to 22.176 million), respectively. Women were generally more
      affected than men. Cataract was the most frequent cause of blindness in all
      subregions in 1990, but macular degeneration and uncorrected refractive error
      became the most frequent causes of blindness in 2010 in all high-income
      countries, except for Eastern/Central Europe, where cataract remained the leading
      cause. Glaucoma and diabetic retinopathy were fourth and fifth most common causes
      for blindness for all regions at both times. Uncorrected refractive error,
      followed by cataract, macular degeneration, glaucoma and diabetic retinopathy,
      was the most common cause for MSVI in 1990 and 2010. CONCLUSIONS: In highly
      developed countries, prevalence of blindness and MSVI has been reduced by 50% and
      38%, respectively, and the number of blind people and people with MSVI decreased
      by 17.4% and 12.6%, respectively, even with the increasing number of older people
      in the population. In high-income countries, macular degeneration has become the
      most important cause of blindness, but uncorrected refractive errors continue to
      be the leading cause of MSVI.

PMID- 24665134
TI  - Practice guidelines for the diagnosis and management of microcytic anemias due to
      genetic disorders of iron metabolism or heme synthesis.
AB  - During recent years, our understanding of the pathogenesis of inherited
      microcytic anemias has gained from the identification of several genes and
      proteins involved in systemic and cellular iron metabolism and heme syntheses.
      Numerous case reports illustrate that the implementation of these novel molecular
      discoveries in clinical practice has increased our understanding of the
      presentation, diagnosis, and management of these diseases. Integration of these
      insights into daily clinical practice will reduce delays in establishing a proper
      diagnosis, invasive and/or costly diagnostic tests, and unnecessary or even
      detrimental treatments. To assist the clinician, we developed evidence-based
      multidisciplinary guidelines on the management of rare microcytic anemias due to
      genetic disorders of iron metabolism and heme synthesis. These genetic disorders
      may present at all ages, and therefore these guidelines are relevant for
      pediatricians as well as clinicians who treat adults. This article summarizes
      these clinical practice guidelines and includes background on pathogenesis,
      conclusions, and recommendations and a diagnostic flowchart to facilitate using
      these guidelines in the clinical setting. 

PMID- 24665136
TI  - Influenza virus H1N1 activates platelets through FcgammaRIIA signaling and
      thrombin generation.
AB  - Platelets play crucial functions in hemostasis and the prevention of bleeding.
      During H1N1 influenza A virus infection, platelets display activation markers.
      The platelet activation triggers during H1N1 infection remain elusive. We
      observed that H1N1 induces surface receptor activation, lipid mediator synthesis,
      and release of microparticles from platelets. These activation processes require
      the presence of serum/plasma, pointing to the contribution of soluble factor(s).
      Considering that immune complexes in the H1N1 pandemic were reported to play a
      pathogenic role, we assessed their contribution in H1N1-induced platelet
      activation. In influenza-immunized subjects, we observed that the virus scaffolds
      with immunoglobulin G (IgG) to form immune complexes that promote platelet
      activation. Mechanistically, this activation occurs through stimulation of low
      affinity type 2 receptor for Fc portion of IgG (FcgammaRIIA), a receptor for
      immune complexes, independently of thrombin. Using a combination of in vitro and
      in vivo approaches, we found that the antibodies from H3N2-immunized mice
      activate transgenic mouse platelets that express FcgammaRIIA when put in the
      presence of H1N1, suggesting that cross-reacting influenza antibodies suffice.
      Alternatively, H1N1 can activate platelets via thrombin formation, independently
      of complement and FcgammaRIIA. These observations identify both the adaptive
      immune response and the innate response against pathogens as 2 intertwined
      processes that activate platelets during influenza infections. 

PMID- 24665135
TI  - A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains
      causing heart amyloidosis.
AB  - Poor prognosis and limited therapeutic options characterize immunoglobulin light
      chain (AL) amyloidosis with major heart involvement. Reliable experimental models
      are needed to study light-chain (LC)/heart interactions and to explore strategies
      for prevention of cardiac damage. We have exploited the nematode Caenorhabditis
      elegans as a novel tool, because its pharynx is evolutionarily related to the
      vertebrate heart. Our data demonstrate that the pharyngeal pumping of C elegans
      is significantly and selectively reduced by LCs from AL patients suffering from
      cardiomyopathy, but not by amyloid LCs with different organ tropism or
      nonamyloidogenic LCs from multiple myeloma. This functional alteration is
      dependent on the LC concentration and results in persistent pharyngeal
      dysfunction and in a significant reduction of the worms' lifespan. These
      manifestations are paralleled by an increase of mitochondrial reactive oxygen
      species and can be prevented by treatment with antioxidant agents. In conclusion,
      these data indicate that this nematode-based assay is a promising surrogate model
      for investigating the heart-specific toxicity of amyloidogenic LCs and for a
      rapid screening of new therapeutic strategies. 

PMID- 24665137
TI  - Doctor one of two people to face first UK prosecutions for female genital
      mutilation.

PMID- 24665138
TI  - Meningitis B vaccine to be introduced in UK after U turn on its cost
      effectiveness.

PMID- 24665139
TI  - Medical fraudster Trudeau sentenced to 10 years in prison.

PMID- 24665140
TI  - Lateral radiograph of the knee.

PMID- 24665141
TI  - Ballistic injury.

PMID- 24665142
TI  - Inquiry into London NHS calls for new strategic health authority to plan and
      commission services.

PMID- 24665143
TI  - US court will hear religious challenge to health law's contraceptive mandate.

PMID- 24665144
TI  - Robust Estimation of the Parameters of g - and - h Distributions, with
      Applications to Outlier Detection.
AB  - The g - and - h distributional family is generated from a relatively simple
      transformation of the standard normal and can approximate a broad spectrum of
      distributions. Consequently, it is easy to use in simulation studies and has been
      applied in multiple areas, including risk management, stock return analysis and
      missing data imputation studies. A rapidly convergent quantile based least
      squares (QLS) estimation method to fit the g - and - h distributional family
      parameters is proposed and then extended to a robust version. The robust version
      is then used as a more general outlier detection approach. Several properties of
      the QLS method are derived and comparisons made with competing methods through
      simulation. Real data examples of microarray and stock index data are used as
      illustrations.

PMID- 24665145
TI  - RBP4 gene variants are associated with insulin resistance in women with previous
      gestational diabetes.
AB  - OBJECTIVE: This study aimed to examine possible genetic effects of some retinol
      binding protein-4 (RBP4) single nucleotide polymorphisms (SNPs) on the risk of
      gestational diabetes mellitus (GDM). In addition, the SNPs were examined for
      their possible association with insulin resistance at 6 weeks after delivery.
      METHODS: This was a prospective study of 100 women with GDM and 100 participants
      with normal gestation who were evaluated at gestational week 30 and 6 weeks
      postpartum. Three SNPs of RBP4 (rs3758539, rs116736522, and rs34571439) were
      genotyped using TaqMan assay. The genotype distributions between GDM patients and
      normal controls were analyzed using logistic regression models. In addition,
      differences in clinical characteristics among subjects grouped by genotype were
      assessed using the analysis of covariance test. RESULTS: The frequencies of the
      rare alleles were not significantly different between GDM patients and controls.
      However, we identified two variants rs3758539 and rs34571439 associated with
      insulin levels and insulin resistance in women with previous GDM. CONCLUSION:
      Noncoding SNPs of the RBP4 gene are not associated with GDM, but two SNPs showed
      associations with insulin resistance and insulin levels in women with prior GDM.
      Additional studies with increased sample size will be necessary in other GDM
      cohorts.

PMID- 24665146
TI  - Low paraoxonase 1 activity predicts mortality in surgical patients with sepsis.
AB  - INTRODUCTION: State of severe oxidative stress is encountered in sepsis.
      Paraoxonase 1 (PON1) protects against oxidative stress but also undergoes
      inactivation upon that condition. We investigated PON1 activity in surgical
      patients with sepsis in relation to oxidative stress status, inflammation,
      disease severity, and survival. METHODS: Prospective observational study. Sixty
      nine surgical patients with sepsis were compared to 69 age/sex matched healthy
      controls. PON1 paraoxonase and diazoxonase activities, selected biochemical,
      hematological and oxidative stress parameters were measured on admission to ICU
      and 24, 48, 72, and 96 hours later. Disease severity scores were calculated
      daily. RESULTS: Septic patients had significantly lower PON1 activities compared
      to control group at all time points. PON1 activities had good capacity to
      differentiate septic patients from healthy controls. Low PON1 activities were
      associated with higher disease severity scores and higher risk of death.
      Correlation between PON1 activity and markers of inflammation failed to reach
      significance. Decrease in PON1 activity was correlated with an increase in
      reducing components in plasma. CONCLUSION: Our study demonstrated lower PON1
      activity in surgical patients with sepsis compared to healthy controls. PON1
      activity also reflected severity of the disease. Low PON1 activity was associated
      with higher mortality of surgical patients with sepsis.

PMID- 24665148
TI  - Knowledge, awareness and practice regarding needle stick injuries in dental
      profession in India: A systematic review.
AB  - BACKGROUND: Hundreds of thousands of healthcare workers remain susceptible to
      deadly viruses throughout the year, including blood-borne pathogens. Needle stick
      injuries (NSI) constitute one of the most common occupational health hazards in
      healthcare profession. Dental professionals are at more risk of acquiring NSI due
      to their limited and restricted working area. The present systematic review was
      carried out to determine knowledge, awareness and practice regarding NSI in
      dental professionals and students in India. MATERIALS AND METHODS: A systematic
      review of cross-sectional studies available in the literature on the knowledge,
      attitude and practice among dental professionals and students in India was
      carried out. We identified relevant articles through electronic and manual search
      such as Pubmed and MEDLINE. Two investigators independently identified studies
      that were included in the review. RESULTS: Four articles were finally selected
      for inclusion in the review. All the studies were done involving dental students;
      89.23% of the students had correct knowledge about NSI and 91.55% of the students
      had adequate level of awareness regarding its management in one of the studies.
      Also, 89% of students in one of the studies were aware of taking post-exposure
      prophylaxis after accidental NSI. In another study, 44% of the students destroyed
      the needles using a needle destroyer and 15% destroyed them in puncture-resistant
      containers. CONCLUSION: The knowledge and awareness of the dental students is
      adequate, although there is considerable variation in practice and management of
      NSI among different studies. There is a need for more studies involving dental
      professionals.

PMID- 24665147
TI  - Serum anticholinergic activity: a possible peripheral marker of the
      anticholinergic burden in the central nervous system in Alzheimer's disease.
AB  - We review the utility of serum anticholinergic activity (SAA) as a peripheral
      marker of anticholinergic activity (AA) in the central nervous system (CAA). We
      hypothesize that the compensatory mechanisms of the cholinergic system do not
      contribute to SAA if their system is intact and that if central cholinergic
      system deteriorates alone in conditions such as Alzheimer's disease or Lewy body
      dementia, CAA and SAA are caused by way of hyperactivity of inflammatory system
      and SAA is a marker of the anticholinergic burden in CNS. Taking into account the
      diurnal variations in the plasma levels of corticosteroids, which are thought to
      affect SAA, it should be measured at noon or just afterward. 

PMID- 24665149
TI  - Aetio-pathogenesis of breast cancer.
AB  - This is a literature review on the aetiology and pathogenesis of breast cancer,
      which is the most common cancer worldwide, and the second leading cause of cancer
      death, especially in Western countries. Several aetiological factors have been
      implicated in its pathogenesis, and include age, genetics, family history, diet,
      alcohol, obesity, lifestyle, physical inactivity, as well as endocrine factors.
      These factors act separately or together in the causation of breast cancer. More
      recently, triple negative breast cancer has been described in certain categories
      of patients and is associated with poorer prognosis and earlier recurrence
      compared with the conventional breast cancer. Therefore, adequate knowledge of
      these factors is important in identifying high risk groups and individuals, which
      will help in screening, early detection and follow-up. This will help to decrease
      the morbidity and mortality from this life-threatening disease. 

PMID- 24665150
TI  - Interferon-gamma treatment kinetics among patients with active pulmonary
      tuberculosis.
AB  - INTRODUCTION: Interferon-gamma (IFN-gamma) is essential for defence against
      Mycobacterium tuberculosis; however, levels in patients with active tuberculosis
      (TB) and changes during treatment have not been documented in our tuberculosis
      patients in Nigeria, hence this study has been carried out. OBJECTIVE: To
      determine variations, treatment kinetics, and predictive value of IFN-gamma
      levels during treatment of active tuberculosis. DESIGN: Patients with pulmonary
      tuberculosis were recruited and subsequently followed up for 3 months during
      treatment with anti-TB. Peripheral blood was collected for IFN-gamma assays, C
      reactive protein and others followed by a Mantoux test. IFN-gamma levels produced
      by stimulation with TB antigens were determined by ELISA and repeated measurement
      of IFN-gamma were done at 1 and 3 months of anti-TB therapy. Chi Associations and
      correlations between IFN-gamma were determined. Regression analysis was done to
      determine association between serial IFN-gamma and treatment outcome. RESULTS: We
      recruited 47 patients with active tuberculosis with a mean age of 34.8 +/- 3.6
      years and M:F ratio of 1.12:1. Six (11%) were HIV positive. The mean level of IFN
      gamma induced by TB antigens was 629 +/- 114.1 pg/ml, higher for HIV-negative PTB
      patients compared with HIV-positive PTB patients, 609.78 +/- 723.9 pg/ml and
      87.88 +/- 130.0 pg/ml, respectively, P-value = 0.000. The mean level of IFN-gamma
      induced by TB antigen increased significantly from 629 +/- 114.1 pg/ml to 1023.46
      + 222.8 pg/ml, P-value = 0.03 and reduced to 272.3 +/- 87.7 pg/ml by the third
      month on anti-TB drugs, P-value = 0.001. Negative correlation was observed
      between the mean of baseline and chest X-ray involvement, P = 0.03. There was no
      significant correlation between sputum smear grade with baseline and follow-up
      IFN-gamma levels. Three-month IFN-gamma level among cured patients were higher
      than those with treatment failure, regression analysis showed that it does not
      predict outcome. CONCLUSION: IFN-gamma may be useful in early detection and
      monitoring response; however, large scale studies are needed.

PMID- 24665153
TI  - Trends of tuberculosis prevalence and treatment outcome in an under-resourced
      setting: The case of Enugu state, South East Nigeria.
AB  - BACKGROUND: The burden of tuberculosis (TB) in Nigeria is high. Unfortunately,
      the data from the TB programme of the States' ministries of health are usually
      unpublished, which possibly contribute to the prevailing ignorance and poor
      attitude of Nigerians to the disease. This study determined the trends of TB
      burden and treatment outcome in Enugu state, Nigeria; and relate the State's
      disease burden to that of the Nation. MATERIALS AND METHODS: A descriptive study
      of secondary data from the TB control programme, Ministry of Health, Enugu state,
      the National annual report of 2008, and World Health Organisation (WHO) TB
      database for the 10-year period of 2000-2009. RESULTS: The number of female TB
      cases was higher than males within the 0-14 age group only. The annual number of
      all TB cases showed a rising trend from 914 cases in the year 2000 to 1684 in
      2009; but the proportion of new sputum smear (ss+) pulmonary tuberculosis (PTB)
      cases declined (Trend X(2) = 7.37, P = 0.007). The average number of extra
      pulmonary TB cases increased fourfold from 2000-2004 to 2005-2009 (36 versus 150
      cases). The median treatment success rate was 82% (range: 78-85). For the period
      2004-2008, 2.0% of all new ss + PBT cases reported in Nigeria, originated from
      Enugu state. The proportion of new ss + PTB reported in Enugu state was
      significantly higher than national value (59.6% versus 52.6%) [P < 0.001, OR =
      1.33 (95% CI: 1.26, 1.40)]. CONCLUSION: The burden of TB in Enugu state of
      Nigeria had increased over the period reviewed. However, the State's contribution
      to the disease burden in Nigeria was low.

PMID- 24665152
TI  - Assessment of radiation protection practices among radiographers in Lagos,
      Nigeria.
AB  - BACKGROUND: Use of ionising radiation in diagnostic radiography could lead to
      hazards such as somatic and genetic damages. Compliance to safe work and
      radiation protection practices could mitigate such risks. The aim of the study
      was to assess the knowledge and radiation protection practices among
      radiographers in Lagos, Nigeria. MATERIALS AND METHODS: The study was a
      prospective cross sectional survey. Convenience sampling technique was used to
      select four x-ray diagnostic centres in four tertiary hospitals in Lagos
      metropolis. Data were analysed with Epi- info software, version 3.5.1. RESULTS:
      Average score on assessment of knowledge was 73%. Most modern radiation
      protection instruments were lacking in all the centres studied. Application of
      shielding devices such as gonad shield for protection was neglected mostly in
      government hospitals. Most x-ray machines were quite old and evidence of quality
      assurance tests performed on such machines were lacking. CONCLUSION:
      Radiographers within Lagos metropolis showed an excellent knowledge of radiation
      protection within the study period. Adherence to radiation protection practices
      among radiographers in Lagos metropolis during the period studied was, however,
      poor. Radiographers in Lagos, Nigeria should embrace current trends in radiation
      protection and make more concerted efforts to apply their knowledge in protecting
      themselves and patients from harmful effects of ionising radiation.

PMID- 24665151
TI  - Cardiac autonomic dysfunction in sickle cell anaemia and its correlation with QT
      parameters.
AB  - BACKGROUND: Abnormalities of QT parameters together with cardiac autonomic
      neuropathy (CAN) confer significant risks of cardiac morbidity and mortality in
      patients with diabetes mellitus. We questioned whether or not CAN influences
      occurrence of QT interval prolongation and dispersion in patients with sickle
      cell anaemia (SCA). MATERIALS AND METHODS: Forty stable adult sickle cell
      patients with 44 healthy haemoglobin AA controls were studied. Baseline
      electrocardiograms were obtained and cardiovascular autonomic function tests were
      performed using standard protocols. RESULTS: Mean corrected QT (QTc) in sickle
      cell patients was significantly higher (P = 0.001) than the mean of controls.
      Similarly, mean QT dispersion (QTcd) was higher (P = 0.001) in the former than in
      the latter. Mean QTc in patients with CAN was longer than patients with normal
      autonomic function (461 +/- 26 ms versus 411 +/- 23 ms), P = 0.001 (OR of 17.1,
      CI 3.48-83.71). Similarly, QTcd was higher (P = 0.001) in patients with CAN than
      those with normal cardiac autonomic function. Positive correlations were found
      between CAN with QTc and QTcd (r = 0.604, P = 0.001, r = 0.523, P = 0.001,
      respectively). CONCLUSION: CAN is a risk factor for abnormalities of QT
      parameters in SCA and both may be harbinger for cardiac death.

PMID- 24665154
TI  - A review of neonatal tetanus in University of Maiduguri Teaching Hospital, North
      eastern Nigeria.
AB  - BACKGROUND: Neonatal tetanus is a vaccine preventable disease and is a leading
      cause of neonatal mortality in developing countries. The effectiveness of
      immunization and hygienic umbilical cord care practices in the prevention of the
      disease has been established. OBJECTIVE: The objective of this study was to audit
      the scourge of neonatal tetanus in a tertiary health facility in a resource
      limited setting. MATERIALS AND METHODS: The study was a retrospective study. Case
      notes of neonates admitted with clinical diagnosis of tetanus into the Special
      Care Baby Unit (SCBU) between January 2009 and December 2010 were retrieved and
      evaluated to identify socio-demographic and clinical characteristics, mode of
      acquisition and severity of the disease, presence of co-morbidities, duration of
      hospital stay and outcome. RESULTS: Most of the mothers had no tetanus
      immunization (66.7%) and the main social class of the children was class V
      (45.1%) and IV (41.2%), respectively. Only 29.4% of the mothers attended ante
      natal care (ANC) while majority of the patients were delivered at home (94.1%).
      Half of the neonates presented with the severe form of the disease (51.0%).
      Sepsis is a prominent co-morbidity (59.2%). Morality was high with case fatality
      of 66.7%. CONCLUSION: This high prevalence of neonatal tetanus with high
      mortality is not only disappointing but unacceptable in the 21(st) century.
      Therefore, all efforts must be re-focused on current preventive strategies while
      pursuing new areas such as slow-release mono-dose tetanus vaccine and school
      health programme as well as advocacy on political will for the sustainability of
      immunization programmes of women of child-bearing age.

PMID- 24665156
TI  - Routine haemoglobin electrophoresis screening in day case herniotomy in Nigerian
      children: Is it evidence-based?
AB  - BACKGROUND: To determine the prevalence of haemoglobinopathies in children who
      require day case herniotomy in our centre and ascertain if routine screening is
      necessary in all patients who require herniotomy. MATERIALS AND METHODS: A 12
      month retrospective analysis of patients requiring herniotomy in our centre. Data
      including age, sex, diagnosis, haemoglobin electrophoresis status, surgical
      outcome and hospital stay were analysed. RESULTS: Ninety-five patients had
      complete records. There were 84 boys and 11 girls. M:F ratio: 7.6:1. The mean age
      was 3.2 +/- 0.6 years. Fifty-five point eight per cent of the patients had right
      inguinal hernias while 35.8% had left inguinal hernias. Eight patients (8.4%) had
      bilateral inguinal hernias. Twenty-six patients (27.4%) had haemoglobinopathies
      while 69 patients (72.6%) had homozygous Haemoglobin A. The Sickle Cell trait
      (HbAS) was found in 22 patients (23.2%) while the HbAC was found in three
      patients (3.2%). One patient (1.1%) had Sickle Cell disease (Haemoglobin SS). He
      had had blood transfusion and previous history of jaundice. All patients survived
      and all patients were discharged on the day of surgery (mean hospital stay: 4hrs
      (range: 2.5 hrs-12 hrs)) except the patient with Sickle Cell disease who was
      admitted a day before surgery and discharged a day after the operation.
      CONCLUSION: One in four children coming for day case herniotomy in our centre had
      the Sickle Cell trait while only 1% had the Sickle Cell disease. These findings
      are in keeping with the prevalence in the Nigerian population. Routine screening
      may not be necessary for all patients coming for herniotomy in our centre. Clear
      indication(s) should be outlined for screening.

PMID- 24665155
TI  - Association of body mass index and abdominal adiposity with atherogenic lipid
      profile in Nigerians with type 2 diabetes and/or hypertension.
AB  - BACKGROUND: We explored the relationship between anthropometric indices (obesity
      and abdominal adiposity) and the presence of an atherogenic lipid profile in
      Nigerians with major cardiovascular risk factors (type 2 diabetes mellitus-T2DM,
      hypertension-HBP, and concomitant disease). MATERIALS AND METHODS: Using a
      prospective design, 278 patients with T2DM, HBP, or concomitant disease,
      attending out-patient diabetes and hypertension clinics at a tertiary institution
      in Nigeria were evaluated. All patients were cholesterol-lowering oral medication
      naomicronve. Demographic and clinical data and anthropometric measurements were
      documented. Fasting lipid profiles were measured in all cases. The cut-off points
      for defining dyslipidaemia were: Elevated total cholesterol (TC) (mg/dL) >=200,
      elevated low-density lipoprotein cholestrol (LDL-C) (mg/dL) >=100, low high
      density lipoprotein cholesterol (HDL-C) (mg/dL) <40 for men and <50 for women,
      and high triglycerides (TG) (mg/dL) >=150 mg/dL. RESULTS: We found a
      significantly higher mean BMI (kg/m(2)) in the HBP group (30.5 +/- 6.0) compared
      to T2DM (28.1 +/- 5.9) and concomitant HBP and T2DM groups (29.4 +/- 5.2) (ANOVA;
      P = 0.02). The most frequent dyslipidaemia was elevated LDL-C in 92 (96.8%) HBP,
      73 (85.9%) T2DM and 79 (80.6%) concomitant disease. The frequency of low HDL-C
      was highest in T2DM (68.2%) compared to the other 2 groups (P = 0.03).
      CONCLUSIONS: Only TG levels were found to relate with any anthropometric index
      (waist circumference (WC) in this case) in Nigerians with major cardiovascular
      risk factors in this study. Routine anthropometric indices do not appear to be
      reliable surrogates for atherogenicity measured by abnormalities in TC, LDL-C and
      HDL-C.

PMID- 24665157
TI  - Retarded hippocampal development following prenatal exposure to ethanolic leaves
      extract of Datura metel in wistar rats.
AB  - BACKGROUND: Datura metel contains atropine alkaloids and has been used to treat
      complication like asthma and, bronchitis, because of its anticholinergic
      properties. AIM: This study aimed to determine the prenatal effects of ethanolic
      extract of D. metel leaves exposure on the development of hippocampus. MATERIALS
      AND METHODS: Twenty rats (12 females and 8 males) were purchased. The females
      were grouped into four groups (A_D). Group A were given 500 mg/kg body weight of
      the extract on the first day of fertilization to the end of gestation period,
      Group B were given 500 mg/kg body weight on the 8(th) day of fertilization to the
      end of gestation period, Group C were given 500 mg/kg body weight on 15(th) day
      of fertilization to the end of gestation period and Group D were given normal
      saline throughout the gestation period. RESULTS: Rats in Group A showed no
      implantation, rats in Group B had abortion on the 7(th) day after administration,
      and rats in Group C gave birth with their litters showing retarded hippocampus
      development and neural degeneration and rats in Group D (control) showed normal
      development. CONCLUSION: Ethanolic extract of D. metel leaf is teratogenic in the
      late stage of pregnancy, is abortificient and can serve as a contraceptive.

PMID- 24665158
TI  - Risk factors and perinatal outcome of uterine rupture in a low-resource setting.
AB  - BACKGROUND: Uterine rupture has continued to be a catastrophic feature of
      obstetric practice especially in the low-resource settings. This study determined
      the incidence, predisposing factors, treatment options and feto-maternal outcome
      of ruptured uterus. MATERIALS AND METHODS: A 10-year retrolective study of all
      cases of uterine ruptures that were managed in Nnamdi Azikiwe University Teaching
      Hospital, Nnewi, Nigeria between 1st January, 2001 and 31st December, 2010 was
      undertaken. The proforma was initially used for data collection, which was
      transferred to a data sheet before entering them into the Epi-info software.
      Analysis was done using Epi info 2008 (version 3.5.1). RESULTS: Out of 5,585
      deliveries over the study period, 47 had uterine rupture, giving an incidence of
      0.84% or 1 in 119 deliveries. All the patients were multiparous and majority
      (63.8%) was unbooked. Traumatic (iatrogenic) rupture predominated (72.1%).
      Uterine repair with (55.8%) or without (34.9%) bilateral tubal ligation was the
      commonest surgery performed. Case fatality rate was 16.3%, while the perinatal
      mortality rate was 88.4%. Average duration of hospitalization following uterine
      rupture was 10.3 days. CONCLUSION: Uterine rupture constituted a major obstetric
      emergency in the study hospital and its environs. The incidence, maternal and
      perinatal mortalities were high. The traumatic/iatrogenic ruptures constituted
      the majority of cases, hence, majority of the cases are preventable. There is
      therefore a dire need for education of our women on health-related issues,
      utilization of available health facilities, adequate supervision of labour and
      provision of facilities for emergency obstetric care.

PMID- 24665159
TI  - Orthopaedic surgical treatment delays at a tertiary hospital in sub Saharan
      Africa: Communication gaps and implications for clinical outcomes.
AB  - BACKGROUND: Delay in surgical treatment is a source of distress to patients and
      an important reason for poor outcome. We studied the delay before carrying out
      scheduled operative orthopaedic procedures and the factors responsible for it.
      MATERIALS AND METHODS: This prospective study was carried out between March 2011
      and December 2012. Temporal details of the surgical procedures at our hospital
      were recorded in a proforma including the patients' perception of the causes of
      the delay to surgery. Based on the urgency of the need for surgery, patients were
      classified into three groups using a modification of the method employed by
      Lankester et al. Data was analyzed using the Statistical Package for the Social
      Sciences, version 17.0. Predictors of surgical delay beyond 3 days were
      identified by logistic regression analysis. RESULTS: Two hundred and forty-nine
      patients with a mean age 36.2 +/- 19.2 years and M:F ratio 1.3 were recruited.
      34.1% were modified Lankester group A, 45.4% group B and 20.5% group C. 47
      patients (18.9%) had comorbidities, hypertension being the commonest (22
      patients; 8.8%). Median delay to surgery was 4 days (mean = 17.6 days). Fifty
      percent of emergency room admissions were operated on within 3 days, the figure
      was 13% for other admissions. Lack of theatre slot was the commonest cause of
      delay. There was full concordance between doctors and patients in only 70.7%
      regarding the causes of the delay. In 15.7%, there was complete discordance.
      Logistic regression analysis confirmed modified Lankester groups B and C (P =
      0.003) and weekend admission (P = 0.016) as significant predictors of delay to
      surgery of >3 days. CONCLUSION: Promptness to operative surgical care falls short
      of the ideal. Theatre inefficiency is a major cause of delay in treating surgical
      patients in our environment. Theatre facilities should be expanded and made more
      efficient. There is a need for better communication between surgeons and patients
      about delays in surgical treatment.

PMID- 24665160
TI  - Serum alpha-fetoprotein level is higher in hepatitis C than hepatitis B infected
      chronic liver disease patients.
AB  - BACKGROUND: The frequency of raised serum alpha-fetoprotein may vary in relation
      to hepatitis B or C infection in chronic liver disease (CLD). The study evaluated
      the frequency of hepatitis B and C in patients with chronic liver disease and
      correlated the levels of serum alpha-fetoprotein with hepatitis B and C infection
      in the patients. MATERIALS AND METHODS: Eighty-six patients with CLD were
      recruited for the study. Fifty subjects, with no CLD were used as control.
      Hepatitis B surface Antigen (HBsAg) and hepatitis C antibody were determined
      using enzyme-linked immunosorbent assay (ELISA) technique (Human diagnostics,
      Germany and HCV Murex 40 Anhet laboratories, USA) while liver function tests were
      evaluated using express plus chemistry auto analyzer. Alpha-fetoprotein was
      assayed using ELECSYS 1010 auto analyser. RESULTS: There were 60 males and 26
      females, with a mean age of 46 + 6.5 years, while the controls were 25 males and
      25 females with a mean age of 41 +/- 2.5 years. Thirty-six subjects (41.7%) were
      seropositive for HBsAg while 24 (27.9%) were seropositive for Hepatitis C Virus
      (HCV) antibody. The mean alpha fetoprotein level was 359 +/- 9.9 ng/mL while mean
      control value was 1.93 +/- 0.24 ng/mL. Liver function test parameters were
      elevated compared with control subjects (P < 0.001). The increase in serum alpha
      fetoprotein was higher (P < 0.001) in HCV than HBsAg positive patients.
      CONCLUSION: Serum alpha-fetoprotein level was highest in HCV compared to HBsAg
      positive and hepatitis negative patients with CLD.

PMID- 24665161
TI  - A Five (5) chamber heart (Cor Triatriatum) in Infancy: A rare congenital heart
      defect.
AB  - Five-chambered heart is extremely rare in children. We report a case of
      asymptomatic five chamber heart detected in infancy. The patient is 2-day-old and
      managed in a special care baby unit (SCBU) for neonatal sepsis. During routine
      follow-up at the age of 1 month, she was found to have an asymptomatic murmur.
      Echocardiograph reported five-chambered heart, concluding that it is Cor
      triatriatum, supravalvular pulmonary stenosis and secundum atrial septal defect.
      The child is still been followed-up and is still asymptomatic at 7 months. Five
      chambered heart, although rare, can occur even if asymptomatic. 

PMID- 24665162
TI  - Academic Responding During Instruction and Reading Outcomes for Kindergarten
      Students At-risk for Reading Difficulties.
AB  - The purpose of this study was to investigate the academic responding of students
      at-risk for reading difficulties in beginning reading instruction. Opportunities
      for kindergarten students at-risk for reading difficulties to respond
      academically during teacher-facilitated reading instruction in the general
      education classroom were examined in relation to student reading achievement as
      well as social behaviors. Student academic responding during teacher-facilitated
      instruction significantly predicted end of year reading achievement. Teacher
      perceptions of students' social skills (positive correlation) and problem
      behaviors (negative correlation) were significantly correlated with academic
      responding. When academic responding and teacher perceptions of social behaviors
      were examined together, only teacher perceptions of academic competence and
      problem behaviors predicted spring outcomes.

PMID- 24665165
TI  - Editor's desk - Own laws of work.

PMID- 24665163
TI  - Effect of the administration of alpha-lipoic acid on contrast sensitivity in
      patients with type 1 and type 2 diabetes.
AB  - The aim of this study was to estimate the effects of oral supplementation of
      alpha-lipoic acid (ALA) on contrast sensitivity (CS) in patients with type 1
      diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The study included
      12 patients with T1DM aged 43+/-12 years, 48 patients with T2DM aged 59+/-10
      years, and 20 control subjects aged 33+/-8 years. Patients from each studied
      group, including the control group, were randomly assigned to receive 300 mg of
      ALA orally once daily for 3 months. CS was evaluated with the Functional Acuity
      Contrast Test (FACT, Stereo Optical). In the group of patients with T1DM
      receiving ALA for 3 months CS remained stable and improved in those with T2DM.
      Reduction of CS in both T1DM and T2DM patients without alpha-lipoic acid
      supplementation was observed. In the control group on alpha-lipoic acid
      supplementation, CS improvement was noticed at one spatial frequency. Changes in
      the CS were observed, despite stable visual acuity and eye fundus image in all
      studied subjects. Our study demonstrated that oral administration of alpha-lipoic
      acid had influence on CS in both T1DM and T2DM patients.

PMID- 24665164
TI  - Interleukin-1 receptors are differentially expressed in normal and psoriatic T
      cells.
AB  - This study was carried out to examine the possible role of interleukin-1 (IL-1)
      in the functional insufficiency of regulatory T cells in psoriasis, by comparing
      the expression of IL-1 receptors on healthy control and psoriatic T cells.
      Patients with moderate-to-severe chronic plaque psoriasis and healthy volunteers,
      matched in age and sex, were selected for all experiments. CD4(+)CD25(-) effector
      and CD4(+)CD25(+)CD127(low) regulatory T cells were separated and used for the
      experiments. Expression of the mRNA of IL-1 receptors (IL-1R1, IL-1R2, and sIL
      1R2) was determined by quantitative real-time RT-PCR. Cell surface IL-1 receptor
      expression was assessed by flow cytometry. Relative expression of the signal
      transmitting IL-1 receptor type 1 (IL-1R1) mRNA is higher in resting psoriatic
      effector and regulatory T cells, and activation induces higher IL-1R1 protein
      expression in psoriatic T cells than in healthy cells. Psoriatic regulatory and
      effector T cells express increased mRNA levels of the decoy IL-1 receptors (IL
      1R2 and sIL-1R2) upon activation compared to healthy counterparts. Psoriatic T
      cells release slightly more sIL-1R2 into their surrounding than healthy T cells.
      In conclusion, changes in the expression of IL-1 receptors in psoriatic
      regulatory and effector T cells could contribute to the pathogenesis of
      psoriasis. 

PMID- 24665166
TI  - Blood gas analysis for bedside diagnosis.
AB  - Arterial blood gas is an important routine investigation to monitor the acid-base
      balance of patients, effectiveness of gas exchange, and the state of their
      voluntary respiratory control. Majority of the oral and maxillofacial surgeons
      find it difficult to interpret and clinically correlate the arterial blood gas
      report in their everyday practice. This has led to underutilization of this
      simple tool. The present article aims to simplify arterial blood gas analysis for
      a rapid and easy bedside interpretation. In context of oral and maxillofacial
      surgery, arterial blood gas analysis plays a vital role in the monitoring of
      postoperative patients, patients receiving oxygen therapy, those on intensive
      support, or with maxillofacial trauma with significant blood loss, sepsis, and
      comorbid conditions like diabetes, kidney disorders, Cardiovascular system (CVS)
      conditions, and so on. The value of this analysis is limited by the understanding
      of the basic physiology and ability of the surgeon to interpret the report. Using
      a systematic and logical approach by using these steps would make the
      interpretation simple and easy to use for oral and maxillofacial surgeons. 

PMID- 24665167
TI  - Dental implant survival in diabetic patients; review and recommendations.
AB  - Rising population of diabetic individuals across the world has become a big
      concern to the society. The persistent hyperglycemia may affect each and every
      tissue and consequently results in morbidity and eventually mortality in diabetic
      patients. A direct negative response of diabetes has been observed on oral
      tissues with few contradictions however, little are known about effect of
      diabetes on dental implant treatment and the consequent results. Many studies
      concerned with osteointegration and prognosis of dental implant in diabetic
      patients have been conducted and published since 1994. These studies have been
      critically reviewed to understand the impact of diabetes on the success of dental
      implant and the factors to improve osseointegration and consequently survival of
      dental implant in diabetic patients. Theoretical literatures and studies in
      diabetic animals substantiate high failure rate of implants but most of clinical
      studies indicated statistically insignificant failure of dental implants even in
      moderately uncontrolled diabetic patients. Success of dental implant in well and
      fairly controlled diabetic patients with proper treatment planning, prophylactic
      remedies and adequate postsurgical maintenance appears as good as normal
      individuals. 

PMID- 24665168
TI  - Bisphophonates related osteonecrosis of the jaw.
AB  - OBJECTIVE: With sporadic reporting of BPs related osteonecrosis of jaw and in
      absence of definitive guidelines regarding the management of such patients, the
      dentists and the oral and maxillofacial surgeons need to be updated about this
      issue. The objective of this article was to produce an updated bibliographic
      review of BPs related ONJ. This paper reviews the literature regarding the same
      for better understanding of the problem and its management. BACKGROUND:
      Bisphosphonates (BPs) are potent inhibitors of bone resorption and are widely
      used in the treatment of osteoporosis and other diseases that cause bone mass
      loss, such as Paget's disease, bone metastases, and multiple myeloma, to prevent
      pathological fractures. With increasing use, evidence is emerging that patients
      taking BP drugs are at risk of developing osteonecrosis of the jaws (ONJs),
      sometimes occurring spontaneously, but more commonly following dental extractions
      or oral bone surgery. MATERIALS AND METHODS: A bibliographic search was carried
      out using PubMed, Medline, and search engines ending in April, 2013. The search
      terms used were: Oral BPs, dental implants, and osteonecrosis. CONCLUSION: On the
      basis of available literature, the management of patients on bisphosphonates
      requiring dental treatment is classified according to the duration of BPs
      treatment, method of administration of BPs etc. Dental treatments when planned
      carefully in such patients have a fair to good prognosis.

PMID- 24665169
TI  - Soft tissue cephalometric analysis applied to regional Indian population.
AB  - INTRODUCTION: Importance of soft tissue consideration in establishing treatment
      goals for orthodontics and orthognathic surgery has been recognized and various
      cephalometric analysis incorporating soft tissue parameters have evolved. The
      great variance in soft tissue drape of the human face and perception of esthetics
      exists and normative data based on one population group cannot be applied to all.
      The study was conducted to compare the standard soft tissue cephalometric
      analysis (STCA) norms with norms derived for population of western Uttar Pradesh
      region of India. MATERIALS AND METHODS: The sample consisted of lateral
      cephalograms taken in natural head position of 33 normal subjects (16 males, 17
      females). The cephalograms were analyzed with soft tissue cephalometric analysis
      for orthodontic diagnosis and treatment planning, and the Student's t test was
      used to compare the difference in means between study population and standard
      STCA norms. RESULTS: Compared with established STCA norms, females in our study
      had steeper maxillary occlusal plane, more proclined mandibular incisors, and
      less protrusive lips. Both males and females showed an overall decrease in facial
      lengths, less prominent midface and mandibular structures and more convex profile
      compared with established norms for the White population. CONCLUSIONS:
      Statistically significant differences were found in certain key parameters of
      STCA for western Uttar Pradesh population when compared with established norms.

PMID- 24665171
TI  - Use of anteriolateral wall of maxilla for reconstruction of orbital floor
      fracture: A clinical study.
AB  - PURPOSE: The aim of the present study was to assess the utility of anterolateral
      wall of maxilla as a bone graft to reconstruct the continuity of orbital floor.
      MATERIALS AND METHODS: This study was carried out at Datarkar Institute of
      Maxillofacial Surgery, Pratap Nagar, Nagpur. Out of five patients selected, three
      were male and two were female. All the patients had intact anterolateral wall of
      maxilla on contralateral side. In all the patients the reduction of the zygomatic
      complex fracture was done by Keen's approach. The fractures were stabilized by
      miniplates. From the contralateral sides,bone graft of 1.5 * 2 cm size was
      harvested from which were intact in all the patients. All the patients were
      reviewed at regular interval, initially once every week for 1 month, followed by
      once in every month for next 6 months postoperatively. RESULTS: Five patients
      with orbital floor defects of medium size average 1.16 cm size (range 0.8-1.5 cm)
      were grafted by using autogenous bone graft harvested from anterolateral wall of
      maxilla. All the patients were successfully reconstructed with restoration of the
      orbital wall continuity. We have not come across any complications like
      infection, exposure, and extrusion of the graft. Only one patient did not show
      much improvement in enopthalmous where the size of the defect was large.
      CONCLUSIONS: The use of harvested bone graft from the anterolateral wall of the
      maxilla is better option for the reconstruction of orbital floor defects.

PMID- 24665170
TI  - To evaluate the efficacy of biodegradable plating system for fixation of
      maxillofacial fractures: A prospective study.
AB  - AIMS: The present study was undertaken to evaluate the efficacy of biodegradable
      plating system for fixation of maxillofacial fractures and to study the morbidity
      associated with the use of biodegradable plates and screws. MATERIALS AND
      METHODS: This prospective study consisted of 10 patients with maxillofacial
      fractures requiring open reduction and internal fixation. Fractures with
      infection, comminuted and pathological fractures were excluded. All were plated
      with biodegradable system (Inion CPS) using standard plating principles and
      observed for a total period of 24 weeks. Characteristics of the fractures, ease
      of use of bioresorbable plate/screw system and post operative complications were
      assessed. RESULTS: Of total 10 patients, eight patients were of midface fracture
      and two pediatric patients with mandibular fracture, with nine male and one
      female. The mean age was 32.8 years. Out of 20 plates and 68 screws applied to
      the 10 fractures sites; there were three incidences of screw breakage with no
      other intraoperative difficulties. Paresthesia of the infraorbital nerve was
      present in two patients, and recovered completely in four weeks after surgery.
      Fracture reduction was considered to be satisfactory in all cases. One patient
      developed postsurgical infection and was managed with oral antibiotics and
      analgesics. CONCLUSIONS: Favorable healing can be observed through the use of
      biodegradable plates and screws to stabilize selected midface fractures in
      patients of all ages, as well as mandible fractures in early childhood, however
      further studies with more sample size are required.

PMID- 24665172
TI  - Study over the clinical picture and histopathology of leukoplakia and to
      establish the correlation between causative factors in the patients of Garhwal
      hill region.
AB  - AIMS: This cross-sectional study was conducted to correlate the clinical picture,
      causative factors of leukoplakia with its histopathology in the patients of
      Garhwal hill region. MATERIALS AND METHODS: The study was carried out on indoor
      and outdoor patients of Department of Otorhinolaryngology, HNB Base Hospital,
      Srinagar, Garhwal, Uttarakhand. Patients were interviewed by a predesigned
      questionnaire and clinically examined. Finally, histopathological examination was
      done by using proper technique. STATISTICAL ANALYSIS: The data were analyzed by
      using SPSS version 15. RESULTS: The sample consisted of 90 patients were
      evaluated. Minimum age of presentation was 18 years while the maximum was 65
      years. The majority of patients were in age group of 31-40 years, with male
      predominance. Majority of cases were of minimum dysplasia and minimum of
      carcinoma in situ (CIS). Buccal mucosa is the most common site for leukoplakia,
      while hard palate is the least common site. One case of CIS was reported in
      buccal mucosa, while two cases of CIS were found in specialized mucosa. Smoking
      and pan masala (in both types with or without tobacco mixed) had a direct
      relation with the histological type of leukoplakia, as the amount and duration of
      consumption increased, the severity of dysplasia increased. CONCLUSIONS: Majority
      of cases were males in age group of 31-40 years. Probably, it was due to the
      addiction to smoking and pan masala started early in this region. Severity of
      dysplasia was related to the amount and duration of exposure to smoking and pan
      masala. Buccal mucosa was commonly involved because of general human tendency of
      keeping pan masala in buccal region for a long duration.

PMID- 24665173
TI  - Zygomatic complex fracture: A comparative evaluation of stability using titanium
      and bio-resorbable plates as one point fixation.
AB  - BACKGROUND: The malar bone represents a strong bone on fragile support and its
      processes - frontal, orbital, maxillary and zygomatic are frequently the site of
      fracture. Current study was done to compare the stability of zygomatic complex
      fracture using Biodegradable plates and titanium miniplates with one point
      fixation. MATERIALS AND METHODS: Twenty patients of zygomatic complex fracture
      were randomly selected and divided in two groups which were further divided into
      two subgroups (A, B). Group I patients were treated with titanium miniplate at
      zygomatic buttress and Group II was treated by bio-resorbable plates. One point
      fixation was done either at zygomatic buttress or at frontozygomatic suture and
      it was observed that both the site have been the most favored site of rigid
      internal fixation in terms of stability, aesthetics and prevention of rotation of
      the fracture segment in either vertical or horizontal axis. CONCLUSION: There is
      no significant difference in post operative outcomes between two groups, but
      still bioresorbable system has some advantage over titanium system as these
      plates resorbs over a period of time and does not cause any interference with
      growth and post operative radiotherapy. However application of biodegradable
      system demands highly precised technique.

PMID- 24665174
TI  - Evaluation of temporomandibular joint disc-repositioning surgery with Mitek mini
      anchors.
AB  - PURPOSE: The aim of this study is to evaluate outcome of Mitek mini anchors
      (DePuy Mitek, Raynham, MA) in TMJ discopexy and assess patient satisfaction based
      on MRI findings. PATIENTS AND METHODS: 7 patients suffered from significant pain
      and dysfunction diagnosed on MRI findings as anterior disc displacement without
      reduction selected for this study. Anchor stability, assessment of positional
      changes and roofing were evaluated by postop MRI and OPTGs. Satisfaction was
      assessed with VAS. Preop and postop maximum interincisal opening measurements
      were compared. RESULTS: There was significant difference between preop and posto
      P values of MIO and VAS. All 7 patients noted complete absence of pain at the
      postop 1-year follow-up. Only 1 patient had postop clicking but showed remarkable
      improvement of jaw functions (MIO). The articular disk was observed at its normal
      position in 6 patients except one patient whom MRI confirmed postop partial
      roofing. OPTGs reveal neither radiologic changes around the mini anchors in the
      condylar head nor any positional shifts. CONCLUSION: Disc repositioning with
      Mitek mini anchors represent improvement in post-op VAS scores and clinical
      findings (MIO) based on comparison preop and postop MRI scans and panoramic
      films. However, our study group consists of limited number of patients, further
      studies with more number of cases are required to evaluate the outcomes.

PMID- 24665175
TI  - Single puncture arthrocentesis of temporomandibular joint; introducing a novel
      device: A pilot study.
AB  - INTRODUCTION: Arthrocentesis is a method of irrigating the temporomandibular
      joint (TMJ) with a therapeutic substance. It is usually performed by dual
      puncture with two needles to the joint space. Several studies have shown that
      arthrocentesis of the upper compartment of the TMJ may be a highly effective
      method to restore normal maximal mouth opening and functioning. Nonetheless, the
      classical two needle technique has some limitations, such as the low tolerability
      and difficulty in performing it in the presence of intra-articular adherences.
      The adoption of a single puncture technique for both fluid injection and
      aspiration might have some advantages with respect to the traditional two needle
      approach in terms of time of execution, tolerability, and retention of
      medication. MATERIALS AND METHODS: A single puncture technique with a self
      fabricated device is used to assess the efficacy of this device. This study
      involved 20 patients of age ranging between 20- 64 years diagnosed with TMD.
      Patients follow up done at 3(rd), 14(th), 45(th) and 90(th) day and assessment of
      pain, mouth opening, clicking and deviation done with comparison of pre and post
      operative data. RESULTS: The procedure was successful in all the patients. Most
      of the patients reported reduction in pain more than half of the previous value
      and two patients reported only moderate reduction. There was a clinically
      significant improvement in mouth opening, clicking and deviation. CONCLUSION:
      Arthrocentesis is effective in treating TMJ internal derangement and restoring
      its function. Single puncture arthrocentesis, is a minimally invasive, simple,
      inexpensive & highly efficient procedure that can be performed under local
      anaesthesia.

PMID- 24665176
TI  - Turmeric - A new treatment option for lichen planus: A pilot study.
AB  - Turmeric is dried rhizome of the perennial herbs curcumalonga. It is called Haldi
      in Hindi, turmeric in English, ukon in Japanese. It has been used in Asian
      Medicine since the second millennium BC. It's utility is referred to in the
      ancient Hindu script the Ayurveda. Pathogenesis of the OLP should be taken in
      consideration for the treatment point of view. The Cell mediated immunity to
      secondary antigenic change in oral mucous membrane is thought to play a major
      role in its pathogenesis modified keratocyte surface antigens are the primary
      target for cytotoxic cellular response. Curcumin also been shown to have immune
      modulatory effect involving activation of host macrophages and natural killer
      cells and modulation of lymphocytes mediated function. 

PMID- 24665177
TI  - Cancers of upper gingivobuccal sulcus, hard palate and maxilla: A tertiary care
      centre study in North India.
AB  - INTRODUCTION: Oral cancer is the sixth most common malignancy in the world, and
      the third most common in southeast Asia. Cancers of the upper gingivo-buccal
      complex are uncommon and reported infrequently. In this article, we have assessed
      the clinicopathological features of such cancers and their optimal management.
      MATERIALS AND METHODS: We studied 64 patients with cancer of the upper
      gingivobuccal sulcus (GBS), hard palate, and maxilla seen between February 2009
      and 2013 over a span of 4 years. RESULTS: Of the 64 patients studied, 45 were
      male. The mean age at presentation was 50.59 years (24-80 years). Of the 64, 48
      patients (75%) had a history of substance abuse in the form of tobacco chewing,
      smoking or alcohol. On presentation, 48 of the 64 patients (75%) had T4 disease,
      eight had T3, six had T2 lesion, one had T1 lesion, and 1 patient had a neck
      recurrence with distant metastatic disease (Tx). Out of the 64 patients, 31 had
      clinically palpable neck disease and two patients had distant metastatic disease.
      Of the 64 patients, 58 had squamous cell carcinoma, two had adenoid cystic
      carcinoma of the hard palate and one patient each had melanoma, sarcoma,
      neuroendocrine tumor, and mucoepidermoid carcinoma. Following imaging, 18
      patients (28.13%) underwent upfront surgery and six following neoadjuvant
      chemotherapy. 14 of the 24 patients operated had simultaneous neck dissection. 2
      patients with distant metastasis and 1 with cavernous sinus thrombosis received
      palliative chemotherapy. Out of the 64 patients, the other 24 who were inoperable
      were referred to radiotherapy. CONCLUSION: Upper GBS, hard palate and maxilla
      cancers are uncommon and are diagnosed at an advanced stage due to delay in
      presentation and ignorance of our population. Surgery offers the best form of
      treatment. NACT may be tried to downstage the disease in selected patients with
      borderline operable disease. However, generous margins should be taken post
      chemotherapy with concomitant neck dissection. Adjuvant radiotherapy is
      recommended in selected patients after surgery.

PMID- 24665178
TI  - Distraction osteogenesis for correction of mandibular abnormalities.
AB  - INTRODUCTION: Management of mandibular deformities is challenging. Distraction
      osteogenesis is a relatively new technique with promising results. MATERIALS AND
      METHODS: We selected 12 patients. The osteotomy site decided was proximal to the
      antegonial notch. Latency time was five to seven days. Consolidation period was
      eight weeks in eleven cases and six weeks in one case. RESULTS: In all the
      patients, appreciable lengthening of mandible was achieved. DISCUSSION: The
      greatest advantage of distraction osteogenesis is growth of soft tissue along
      with the growth of hard tissue. This increases post operative stability.

PMID- 24665179
TI  - The epidemiological characteristics of zygomatic complex fractures: A comparison
      between the surgically and non-surgically treated patients.
AB  - INTRODUCTION: This retrospective study is aimed at the documentation of a more
      complete view of epidemiological data with particular focus on the
      characteristics of the surgically and non-surgically treated patients with
      zygomatic complex fractures. MATERIALS AND METHODS: A total of 133 surgically and
      150 non-surgically patients were treated with zygomatic complex fractures in VU
      University medical center Amsterdam from January 2007 to January 2012 were
      analyzed. These patient groups were further subdivided into displaced or non
      displaced fractures and compared with each other according to age, gender and
      trauma etiology. RESULTS: The mean age of all 286 patients was 42.8 years
      (standard deviation [SD: +/-19.8]). Surgically and non-surgically treated
      patients differed in presentation with a significantly overall higher age of
      females, especially within the non-surgically treated patient group with
      displaced fractures (mean age of 59.5 years, SD: +/-27.4). The mean ages of males
      from the different subgroups were more consistent with the overall mean age. The
      main causes were traffic accidents, whereas the contribution of falls and
      assaults depended on age group, gender, treatment management and even fracture
      displacement. CONCLUSIONS: This report provides us important epidemiological data
      of all patients with zygomatic complex fractures. The non-surgically treated
      patient group contained patients of higher age, more females and a fall-related
      cause, compared to the surgically treated patient group. The surgically treated
      patient group showed the same epidemiological characteristics as were
      demonstrated in previous studies.

PMID- 24665180
TI  - Association between mitochondrial C-tract alteration and tobacco exposure in oral
      precancer cases.
AB  - INTRODUCTION: Tobacco exposure is a known risk factor for oral cancer. India is
      home to oral cancer epidemic chiefly due to the prevalent use of both smoke and
      smokeless tobacco. To reduce the related morbidity early detection is required.
      The key to this is detailing molecular events during early precancer stage.
      Mitochondrion is an important cellular organelle involved in cell metabolism and
      apoptosis. Mitochondrial dysfunction is thought to be the key event in
      oncogenesis. Last decade has seen a spurt of reports implicating mitochondrial
      mutations in oral carcinogenesis. However, there are few reports that study
      mitochondrial deoxyribonucleic acid (mtDNA) changes in oral precancer. This study
      aims to understand and link effect of tobacco exposure on mtDNA in oral precancer
      cases. SUBJECTS AND METHODS: A total of 100 oral precancer cases of which 50 oral
      leukoplakia and 50 oral submucous fibrosis were recruited in the study and a
      detailed questionnaire were filled about the tobacco habits. Their tissue and
      blood samples were collected. Total genomic DNA was isolated from both sources.
      Mitochondrial C-tract was amplified and bidirectional sequencing was carried out.
      Mutations were scored over matched blood DNA. RESULTS: There was a significant
      association between the presence of mitochondrial C-tract alteration and duration
      of tobacco exposure. The probability increased with increasing duration of
      tobacco consumption. The risk of having this alteration was more in chewers than
      in smokers. CONCLUSIONS: Tobacco in both form, chewable and smoke, is oncogenic
      and causes early changes in mitochondrial genome and chances increases with
      increasing duration of tobacco consumption.

PMID- 24665181
TI  - Matrix miniplate versus locking miniplate in the management of displaced
      mandibular angle fractures.
AB  - AIM: The purpose of this study was to determine and compare various postoperative
      parameters like ease of operability, plate adaptability, stability etc.,
      associated with use of matrix miniplate versus locking miniplate in the treatment
      of displaced mandibular angle fractures. MATERIALS AND METHODS: The study was
      carried out in the Department of Oral and Maxillofacial surgery, King George's
      Medical College, GM and Associated Hospital, Lucknow. Total 50 patients were
      treated and included in the study. These were divided into two groups of 25 each
      and were treated with two of the standard techniques, i.e., one is matrix
      miniplate osteosynthesis and other is locking miniplate osteosynthesis. These
      patients were evaluated for postoperative complications and the differences
      between the two Groups were assessed. RESULTS: Patients treated by matrix
      miniplate showed better recovery phase postoperatively as compared to locking
      miniplate group. CONCLUSION: Based on this study matrix mini plate osteosynthesis
      may be considered as the better alternative method available for the treatment of
      displaced mandibular angle fractures.

PMID- 24665182
TI  - Temporalis myofascial flap transfer into the oral cavity without zygomatic arch
      osteotomy.
AB  - Among plethora of options, the temporalis myofascial flap remains a workhorse for
      the maxillofacial reconstruction. The inherent advantages include reliable
      vascularity, adequate size, and proximity to the defect. Although contemporary
      surgical techniques provide fair surgical results with low rate of complications,
      their intraoral transposition involve additional surgical trauma by intentional
      fracturing of the zygomatic arch. We have proposed herein a simpler technique of
      temporalis myofascial flap transposition into the oral cavity without zygomatic
      arch osteotomy. 

PMID- 24665183
TI  - Management of unicystic ameloblastoma of the mandible in a 5-year old child.
AB  - Unicystic ameloblastoma rarely seen in first decade of life. This tumour usually
      appears very similar to a non-neoplastic odontogenic cyst and is frequently
      clinically misdiagnosed as dentigerous cyst. The distinction from dentigerous
      cyst is important as unicystic ameloblastoma (UA) unlike dentigerous cyst needs
      different treatment approach and long term follow-up due to its chances of
      recurrence. This report highlights the importance of clinical examination in the
      diagnosis and management of UA in a 5 year old boy. 

PMID- 24665184
TI  - Malignant myoepithelioma of the maxilla posing a diagnostic dilemma.
AB  - Malignant myoepithelioma is an extremely rare tumor of the salivary glands.
      Myoepitheliomas make up less than 1% of all salivary gland tumors. We report of a
      case of malignant myoepithelioma of the upper jaw in a 55-year old man. The tumor
      primarily arose from the maxillary sinus and secondarily involved the palate. A
      diagnosis of pleomorphic adenoma was interpreted, following fine needle
      aspiration cytology and spindle cell tumor, following incision biopsy with a
      dilemma. The surgery consisted of subtotal maxillectomy preserving the infra
      orbital rim and posterior wall of the maxillary sinus, with wide local resection.
      Neck dissection was not carried out. The final histologic diagnosis of the tumor
      proper was made out to be malignant myoepithelioma. Three different diagnoses
      were made in dilemma to reach out the final diagnosis, which was confirmed by
      immunohistochemistry. The case presented and discussed, underscores the
      importance of diagnosis and treatment of this rare clinicopathologic entity. 

PMID- 24665185
TI  - Aggressive monophasic synovial sarcoma involving sublingual gland: First case.
AB  - Synovial sarcoma (SS) of the arising head and neck region is rare. The most
      common site being the hypopharynx. No case of SS from the sublingual of 35-year
      old salivary gland has been reported. We report a case of monophasic SS in
      sublingual gland a female making it the first documented case of English Language
      literature. 

PMID- 24665186
TI  - Chondrosarcoma of body of the mandible.
AB  - Chondrosarcomas are the malignant cartilaginous neoplasms rarely seen in the head
      and neck region. The chondrosarcomas may show an aggressive course and are mostly
      located in relation with anterior maxilla and base of the skull. Chondrosarcomas
      of the body of mandible are infrequent. We report a case of low-grade
      chondrosarcoma of body of mandible, which was treated with a simple excision
      without neck dissection. 

PMID- 24665187
TI  - Extraosseous calcifying cystic odontogenic tumor: An uncommon variant.
AB  - Odontogenic cysts comprise a diverse group of exceptional lesions derived from
      epithelial elements of the tooth-forming apparatus. Calcifying cystic odontogenic
      tumor is a rare odontogenic lesion, which represents about 2% of all odontogenic
      tumors and cysts. It may occur in a central (intraosseous) or peripheral
      (extraosseous calcifying cystic odontogenic tumor [ECCOT]) location. ECCOT in
      contrast to central, tends to affect the older patients, commonly located in the
      anterior lower jaw, is less aggressive and the recurrence is rare. Here, we
      report clinico-pathological and radiographic features of ECCOT located in
      relation to 48 (posterior lower jaw) measuring about 1 cm in the greatest
      diameter in a 17-year-old male. 

PMID- 24665188
TI  - Necrosis of maxilla, nasal, and frontal bone secondary to extensive rhino
      cerebral mucormycosis.
AB  - Mucormycosis is an opportunistic fulminant fungal infection caused by
      zygomycetes. This fungus can cause a variety of infections in human beings,
      particularly in the uncontrolled diabetes mellitus. Zygomycetes impinge into the
      vascular network, resulting in thrombosis and necrosis of the surrounding hard
      and soft tissues. The infection begins in the nose and paranasal sinuses due to
      inhalation of fungal spores and spread to orbital and intracranial structures
      either by direct invasion or through the blood vessels. Sinus mucormycosis is
      often accompanied by a poor prognosis and a high mortality rate. Hence,
      aggressive surgical intervention with antifungal therapy is usually necessary.
      Early diagnosis and prompt treatment can reduce the mortality and morbidity of
      this lethal fungal infection. We report a case of aggressive rhino-cerebral
      mucormycosis in a 58-year-old female patient with uncontrolled diabetes mellitus.

PMID- 24665189
TI  - Bilateral cavernous sinus thrombosis and facial palsy as complications of dental
      abscess.
AB  - Septic cavernous sinus thrombosis (CST) related to dental infection is a rare
      clinical event. The septic CST is a disease of high morbidity and mortality. The
      prompt diagnosis and timely treatment of septic CST is cornerstone of successful
      outcome. The dental infection should be given due attention, as to prevent CST.
      In this case report of immunocompetent female, we highlighted the role of dental
      abscess in producing bilateral CST and facial palsy. The close collaboration
      between dentist and neurologist and early institution of antibiotics led to
      complete recovery at follow-up after 3 months. The dental infection should never
      be neglected as it is the interface of serious intracranial complication like
      CST. 

PMID- 24665191
TI  - Hemisection-hope for last survival.

PMID- 24665190
TI  - Unilateral temporomandibular joint ankylosis with contralateral aplasia.
AB  - The temporomandibular joint (TMJ) is considered as one of the complex joints of
      the human body. Mandibular condylysis is distinguished from condylar aplasia by
      its non-association with aural/facial anomalies, and also as normal development
      appears to proceed until the lytic event occurs. It is further distinguished from
      primary and secondary condylar hypoplasia by the following: Absence of condyle
      rather than it being small, the normal development appears to proceed until the
      lytic event occurs, and its non-association with aural/facial anomalies or
      temporomandibular ankylosis. In the present report, a patient with a unilateral
      missing mandibular condyle with contralateral TMJ ankylosis is presented and the
      treatment is outlined and discussed. 

PMID- 24665192
TI  - Probabilistic method for context-sensitive detection of polyps in CT
      colonography.
AB  - Radiologists can outperform computer-aided detection (CAD) systems for CT
      colonography, because they consider not only local characteristics but also the
      context of findings. In particular, isolated findings are considered as more
      suspicious than clustered ones. We developed a computational method to model this
      problem-solving technique for reducing false-positive (FP) CAD detections in CT
      colonography. Lesion likelihood was estimated from shape and texture features of
      each candidate detection by use of a Bayesian neural network. Context features
      were calculated to characterize the distribution of candidate detections in a
      local neighborhood. A belief network was applied to detect isolated candidates at
      a higher sensitivity than clustered ones. The detection performances of the
      context-sensitive CAD and a conventional CAD were compared by use of leave-one
      patient-out evaluation on 73 patients. Conventional CAD detected 82% of the
      lesions 6 - 9 mm in size with a median of 6 false positives per CT scan, whereas
      context-sensitive CAD detected the lesions at a median of 4 false positives with
      significant increment in overall detection performance. For lesions >=10 mm in
      size, the detection sensitivity was 98% with a median of 7 false positives per
      patient, but the improvement in detection performance was not significant.

PMID- 24665193
TI  - Limit of the Accuracy of Parameter Estimation for Moving Single Molecules Imaged
      by Fluorescence Microscopy.
AB  - In this paper, we consider the problem of the accuracy of estimating the location
      and other attributes of a moving single molecule whose trajectory is imaged by
      fluorescence microscopy. As accuracy in parameter estimation is closely related
      to the Fisher information matrix, we first give a general expression of the
      Fisher information matrix for the estimated parameters for a single object moving
      in three-dimensional (3D) space. Explicit Cramer-Rao lower bound (CRLB)
      expressions are then obtained from the Fisher information matrix for a single
      object moving in the two-dimensional (2D) focus plane with the object trajectory
      being either linear or circular. We also investigate how extraneous noise
      sources, pixelation, parameters of the detection system and parameters of the
      trajectory affect the limit of the accuracy. The results obtained in this paper
      provide insights that enable the experimentalists to optimize their experimental
      setups for tracking single molecules in order to achieve the best possible
      accuracy. They are also applicable to the general problem of tracking an object
      using quantum limited detectors.

PMID- 24665194
TI  - Imperative role of dental pulp stem cells in regenerative therapies: a systematic
      review.
AB  - Stem cells are primitive cells that can differentiate and regenerate organs in
      different parts of the body such as heart, bones, muscles and nervous system.
      This has been a field of great clinical interest with immense possibilities of
      using the stem cells in regeneration of human organ those are damaged due to
      disease, developmental defects and accident. The knowledge of stem cell
      technology is increasing quickly in all medical specialties and in dental field
      too. Stem cells of dental origin appears to hold the key to various cell-based
      therapies in regenerative medicine, but most avenues are in experimental stages
      and many procedures are undergoing standardization and validation. Long-term
      preservation of SHED cells or DPSC is becoming a popular consideration, similar
      to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the
      adult multipotent cells that reside in the cell rich zone of the dental pulp. The
      multipotent nature of these DPSCs may be utilized in both dental and medical
      applications. A systematic review of the literature was performed using various
      internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco,
      Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like "dental pulp
      stem cells", "regeneration", "medical applications", "tissue engineering". DPSCs
      appears to be a promising innovation for the re-growth of tissues however, long
      term clinical studies need to be carried out that could establish some authentic
      guidelines in this perspective. 

PMID- 24665195
TI  - An Insight in to Paget's Disease of Bone.
AB  - Paget's disease of bone (PDB) is a common disorder which may affect one or many
      bones. Although many patients are asymptomatic, a variety of symptoms and
      complications may occur. PDB is a focal disorder of bone turnover characterized
      by excessive bone resorption coupled with bone formation. PDB begins with a
      period of increased osteoclastic activity and bone resorption, followed by
      increased osteoblast production of woven bone that is poorly mineralized. In the
      final phase of the disease process, dense cortical and trabecular bone deposition
      predominates, but the bone is sclerotic and poorly organized and lacks the
      structural integrity and strength of normal bone. This article briefly reviews
      the etiopathogenesis, clinical radiographic and histological features of Paget's
      disease. 

PMID- 24665196
TI  - Zaria universal oxygenator holder phase I.
AB  - INTRODUCTION: The conduct of cardiopulmonary bypass surgery requires the use of
      equipment and devices like the oxygenator. The oxygenator comes in different
      makes and each manufacturer customizes the carrier or 'holder' of this device
      specific to their design. AIM: This paper presents an innovation designed to
      overcome the need to purchase a different holder for every oxygenator thereby
      cutting the cost. MATERIALS AND METHODS: A sheet of iron measuring 1.9 cm (width)
      * 0.1 cm (thickness) was used to design the holder circular main frame. Another
      sheet measuring 2 cm (width) * 0.6 cm (thickness) * 24 cm (length) was used to
      construct a V-shaped handle with the arms of the V attached to the main frame 7
      cm apart. At the narrow base of the handle is a latch requiring two 13-gauge
      screws to attach the holder to the heart-lung machine. Within the circumference
      of the main frame are four T-shaped side arms which grip the oxygenator; located
      at 2, 5, 7 and 11 O'clock positions. The stem of the T consist of a 0.6 cm
      (thickness) * 13 cm (length) rod drilled through the main frame. The cross of the
      T consists of variable lengths of the same sheet as the mainframe attached to the
      stem by a screw mechanism. At the base of the T, is attached a circular handle (4
      cm in diameter) made of 0.4 cm iron rod. RESULT: An oxygenator holder which
      weighs 1.75 kg with a total length of 54 cm (the diameter of the mainframe is 30
      cm). Its advantages include (i) affordability, (ii) materials are locally
      accessible, (iii) versatility (iv) reproducibility. The disadvantages include,
      (i) it requires some time to fit, (ii) caution is required in fitting the
      oxygenator to avoid breakage, (iii) a spanner is required to lock the latch.
      CONCLUSION: The concept of a universal holder is pertinent, especially in
      resource poor environments to avoid purchasing a new holder whenever the usual
      oxygenator common to the centre is unavailable. This device is amenable to
      further modifications to meet the unforeseen challenges.

PMID- 24665197
TI  - Gallbladder Stones Following Ileal Resection for Gangrenous Intussusceptions: A
      Follow-up Study.
AB  - BACKGROUND: Intussusceptions are the most common causes of bowel obstruction in
      infancy and childhood in this environment they present late, resulting in
      gangrene of the intussusception consequently resection of the affected bowel and
      a limited or extended right hemicolectomy (RH) to establish bowel continuity.
      AIM: The aim of the following study is to follow-up these children that had a
      limited ileal resection for gangrenous intussusceptions and document the
      formation of stones in their gallbladders. MATERIALS AND METHODS: A total of 14
      patients who had limited ileal resection during infancy for gangrenous
      intussusceptions were matched with sixteen patients who had manual reduction for
      viable intussusceptions during infancy. Both groups had ultrasound scans of their
      gallbladders to document the formation of stones in their gallbladders. RESULTS:
      No gallbladder stones were found in both groups, however, one male child that had
      a resection and a RH for a gangrenous intussusception at the age of 4 months and
      was seen at an interval of 72 months had a thickened gallbladder on
      ultrasonography, another child, a female child operated on at the age of 6 months
      and seen at an interval of 57 months also had a thickened gallbladder on
      ultrasonography. CONCLUSION: Although no stones were seen, we suggest a prolonged
      follow-up of these patients with either periodic ultrasonography of the their
      gallbladders or with the periodic estimation of their serum bile acids.

PMID- 24665198
TI  - Pilot study on laparoscopic surgery in port-harcourt, Nigeria.
AB  - BACKGROUND: Video-laparoscopic surgery has long been practiced in western
      countries; however documented practice of this minimal access surgical technique
      are recently emanating from Nigeria. To the best of our knowledge, this is the
      first documented study on laparoscopic surgery from the Niger Delta region. AIM:
      To evaluate the feasibility of laparoscopy as a useful tool for management of
      common surgical abdominal conditions in our environment. PATIENTS AND METHODS:
      This was a prospective outcome study of all consecutive surgical patients who had
      laparoscopic procedures in general and pediatric surgery units of our institution
      from August 2011 to December 2012. Data on patient's age, gender, indication for
      surgery, duration of hospital stay and outcome of surgery were collected and
      analyzed. RESULTS: A total of 15 laparoscopic procedures were performed during
      this study period with age range of 2-65 years; mean: 32.27 +/- 17.86 years.
      There were 11 males and four females. Six laparoscopic appendicectomies, one
      laparoscopy-assisted orchidopexy, five diagnostic laparoscopy +/- biopsy, one
      laparoscopic trans-abdominal pre-peritoneal herniorrhaphy for bilateral indirect
      inguinal hernia and two laparoscopic adhesiolysis for small bowel obstruction
      were performed. All were successfully completed except one conversion (6.7%) for
      uncontrollable bleeding in an intra-abdominal tumor. CONCLUSION: The practice of
      laparoscopic surgery in our environment is feasible and safe despite the
      numerous, but surmountable challenges. There is the need for adequate training of
      the support staff and a dedicated theatre suite.

PMID- 24665199
TI  - Pattern of midface trauma with associated concomitant injuries in a nigerian
      referral centre.
AB  - AIM: The aim of this study was to determine the pattern of midface trauma with
      associated concomitant injuries seen in our environment. METHODOLOGY: This was a
      prospective analysis of trauma patients with midfacial injuries presenting at a
      referral center in South West Nigeria. In addition to socio-demographic data, the
      following information was also obtained: Mechanism of injuries, type of midfacial
      injuries, concomitant/associated injuries and treatment. RESULTS: A total of 101
      patients with midfacial injuries were involved. They were made up of 85 males and
      16 females. The 20-29 year age group was mostly affected (44.6%) and the most
      common cause of midface injuries was road traffic accident (91.1%). The zygoma
      was fractured more than any other midfacial bone (46.0%). A total of 144
      associated injuries were recorded among these patients, head and ocular injuries
      accounted for 49 (34%) and 35 (24.3%) respectively. The patients were mostly
      treated conservatively or by closed reduction. CONCLUSION: The rate of head and
      ocular injuries among patients with midfacial injury was high. Knowledge of these
      associated injuries provides useful strategies for patient care and prevention of
      further complications. A multidisciplinary approach is important for optimum
      management of these patients.

PMID- 24665200
TI  - Determinants of mortality in chest trauma patients.
AB  - BACKGROUND: Chest trauma is an important trauma globally accounting for about 10%
      of trauma admission and 25-50% of trauma death. Different types and severity of
      chest trauma in different subsets of patients with varying associated injuries
      result in differing outcomes measured with mortality. Early mitigation of poor
      prognostic factors could result in improved outcome, therefore the need to know
      such factors or determinants of mortality in chest trauma patients. PATIENTS AND
      METHODS: Retrospective and prospective analysis of demographic details, socio
      economic, clinical details, modified early warning signs (MEWS) score on
      presentation, investigation findings, treatment and outcome of chest trauma
      patients who presented to our cardiothoracic surgery unit was undertaken. Data
      were collected and were analyzed using WINPEPI Stone Mountain, Georgia: USD Inc;
      1995 statistical software. RESULTS: A total 149 patients with thoracic trauma
      were studied over a 5 year period constituting 40% of the unit workload. There
      were 121 males and 28 females (81.2% vs. 18.8%; m: f = 4:1) with age range from 7
      to 76 years (mean: 37.42 +/- 12.86 years) and about 55% aged 45 years or below
      and more blunt trauma than penetrating trauma (65.1% vs. 34.9%), but no
      statistical significance amongst the groups on outcome analysis. Sub-grouping of
      the 149 patients according to their on-admission MEWS score shows that 141
      patients had scores of 9 and less and all survived while the remaining eight had
      scores >9 but all died. As independent variables, age, sex and type of chest
      injury did not prove to be correlated with mortality with P values of 0.468,
      1.000 and 1.000 respectively. However presence of associated extra thoracic organ
      injury, high on-admission MEWS score >9, delayed presentation with injury to
      presentation interval longer than 24 h, and severe chest injury as characterized
      by bilateral chest involvement correlated positively with mortality with P values
      of 0.0003, 0.0001, 0.0293 and 0.0236 respectively. CONCLUSION: Associated extra
      thoracic organ injury, high on-admission MEWS score >9, late presentation beyond
      24 h post trauma and severe chest injury with bilateral chest involvement were
      found to be determinants of mortality in chest trauma.

PMID- 24665201
TI  - Early experiences with microvascular free tissue transfer in lagos, Nigeria.
AB  - OBJECTIVES: Microvascular free tissue transfer within our subregion is fraught
      with considerable challenges. We aim to highlight our experiences gained with our
      first fifteen cases of microvascular free tissue transfer at the Lagos University
      Teaching Hospital. We believe our report will be useful to colleagues embarking
      on such reconstructions in similar settings. MATERIALS AND METHODS: The clinical
      records of the first 15 cases of free flaps done at our center were reviewed. The
      indications for surgery, choice of flap, recipient vessels, duration of surgery
      and complications were noted. RESULTS: Fifteen cases were done, 10 flaps
      survived, ten defects occurred following trauma while remaining five followed
      cancer resections. Anterolateral thigh and radial forearm flaps were the most
      common flap used. The mean duration of surgeries was 7.1 hours SD +/- 1.10 hours.
      Our take back rate was 13.3%, with a salvage rate of 50%. Three flaps failed on
      account venous congestion while remaining two failed due to arterial occlusion.
      CONCLUSION: 66.67% free flap success rate recorded reflect our early experiences
      in our institution. We believe meticulous planning, careful vessel selection,
      close flap monitoring as well as improved infrastructural support can lead to
      much better success rates in microvascular reconstruction in our country.

PMID- 24665202
TI  - Breast lumps: a 21-year single-center clinical and histological analysis.
AB  - OBJECTIVE: To review the presentation and histological diagnosis of breast lumps
      of patients seen in Trans Ekulu Hospital Enugu Southeastern Nigeria from 1993 to
      2013 in a period of 21 years. MATERIALS AND METHODS: This is a retrospective
      study covering a period of 21 years. Case notes of patients containing clinical
      information and their histology reports were studied. RESULTS: Only 38% of the
      patients came within 3 months of finding lumps in their breast. One hundred and
      thirty-seven patients (83%) had benign disease, i.e., fibroadenoma, mammary
      dysplasia, cysts, adenomas, tuberculosis, phyllodes tumor, mastitis, and lipoma.
      Only 16.9% i.e., 28 patients had breast cancer, out of which two females were in
      their 20s, and three were males. CONCLUSIONS: Benign breast diseases, i.e.,
      fibroadenoma, fibroadenosis, cysts, adenomas, tuberculosis, phyllodes, mastitis,
      and lipoma are the commoner breast diseases in our locality.

PMID- 24665203
TI  - Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor,
      tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability
      and motility.
AB  - The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases
      regulate many tumorigenesis related cellular processes including cell metabolism,
      cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma
      (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has
      been shown that Akt activation is associated with tumor progression in ATC. Here
      we observed the additive effect between an Akt inhibitor (MK-2206) and a novel
      platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296) in ATC
      therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in
      suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296
      induces additive apoptosis, additive suppression of the Akt signaling pathway, as
      well as additive inhibition of cell migration and invasion of ATC cells.
      Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive
      suppression of ATC tumor growth in vivo. In summary, our studies suggest that the
      combination of Akt and receptor tyrosine kinase inhibitors may be an efficient
      therapeutic strategy for ATC treatment, which might shed new light on ATC
      therapy. 

PMID- 24665204
TI  - Is combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio a
      useful predictor of postoperative survival in patients with esophageal squamous
      cell carcinoma?

PMID- 24665205
TI  - Animal cancer models of skeletal metastasis.
AB  - The bony skeleton is one of the most common sites of metastatic spread of cancer
      and is a significant source of morbidity in cancer patients, causing pain and
      pathologic fracture, impaired ambulatory ability, and poorer quality of life.
      Animal cancer models of skeletal metastases are essential for better
      understanding of the molecular pathways behind metastatic spread and local growth
      and invasion of bone, to enable analysis of host-tumor cell interactions,
      identify barriers to the metastatic process, and to provide platforms to develop
      and test novel therapies prior to clinical application in human patients. Thus,
      the ideal model should be clinically relevant, reproducible and representative of
      the human condition. This review summarizes the current in vivo animal models
      used in the study of cancer metastases of the skeleton. 

PMID- 24665207
TI  - Enhancing Cancer Drug Discovery through Novel Cell Signaling Pathway Panel
      Strategy.
AB  - The link between signaling pathways and diseases suggests the importance of
      pathway analysis for drug discovery. This includes target identification and
      validation, compound mode of action and drug candidate optimization. Here, we
      propose to apply cell signaling pathway panel approaches for oncology drug
      discovery. The strategies and guiding principles of the pathway panel approach
      are discussed. 2 pathway analysis examples with related processes and technology
      platforms are illustrated to identify cancer drugs that target cancer growth and
      metastasis. Finally, we highlight potential challenges and opportunities
      presented by the pathway panel approach. 

PMID- 24665206
TI  - Curcuma Contra Cancer? Curcumin and Hodgkin's Lymphoma.
AB  - Curcumin, a phytochemical isolated from curcuma plants which are used as coloring
      ingredient for the preparation of curry powder, has several activities which
      suggest that it might be an interesting drug for the treatment or prevention of
      cancer. Curcumin targets different pathways which are involved in the malignant
      phenotype of tumor cells, including the nuclear factor kappa B (NFKB) pathway.
      This pathway is deregulated in multiple tumor entities, including Hodgkin's
      lymphoma (HL). Indeed, curcumin can inhibit growth of HL cell lines and increases
      the sensitivity of these cells for cisplatin. In this review we summarize
      curcumin activities with special focus on possible activities against HL cells. 

PMID- 24665208
TI  - The osteoblastic and osteoclastic interactions in spinal metastases secondary to
      prostate cancer.
AB  - Prostate cancer (PC) is one of the most common cancers arising in men and has a
      high propensity for bone metastasis, particularly to the spine. At this stage, it
      often causes severe morbidity due to pathological fracture and/or metastatic
      epidural spinal cord compression which, if untreated, inevitably leads to
      intractable pain, neurological deficit, and paralysis. Unfortunately, the
      underlying molecular mechanisms driving growth of secondary PC in the bony
      vertebral column remain largely unknown. Further investigation is warranted in
      order to identify therapeutic targets in the future. This review summarizes the
      current understanding of PC bone metastasis in the spine, highlighting
      interactions between key tumor and bone-derived factors which influence tumor
      progression, especially the functional roles of osteoblasts and osteoclasts in
      the bone microenvironment through their interactions with metastatic PC cells and
      the critical pathway RANK/RANKL/OPG in bone destruction. 

PMID- 24665209
TI  - Clinical utility of aromatase inhibitors as adjuvant treatment in postmenopausal
      early breast cancer.
AB  - Breast cancer is the most frequently diagnosed malignancy in women, with over
      200,000 new cases diagnosed each year. Adjuvant systemic endocrine therapy has
      demonstrated its benefits in reducing the risk of occult micro metastatic
      infiltration by preventing breast cancer cells from receiving endogenous estrogen
      stimulation. Initial adjuvant treatment with an aromatase inhibitor (AI) is
      considered the standard of care for most postmenopausal women with node-positive
      and high-risk node-negative estrogen receptor (ER)-positive breast cancer.
      Aromatase inhibitors (AIs) are generally preferred over tamoxifen due to their
      effectiveness in preventing breast cancer recurrence post surgery and when
      tamoxifen side effects are to be avoided. When compared with tamoxifen, AIs are
      associated with significantly improved disease-free survival, however no OS
      advantage has been noted. Potential toxicities such as bone loss, dyslipidemia,
      musculoskeletal and cardiovascular health issues should be taken into
      consideration when AIs are to be used. 

PMID- 24665211
TI  - Android shape independent of aerobic fitness: a risk factor for low bone mineral
      content in overweight and obese latina women.
AB  - OBJECTIVE: The link between central adiposity and osteopenia has not been
      extensively studied in Latina women. In particular, the association between
      abdominal weight and bone mineral content (BMC) and bone mineral density (BMD),
      independent of total weight and aerobic capacity, remains uncertain, especially
      in overweight and obese individuals. METHODS: Trunk weight, total body fat mass,
      fat-free mass, BMC, and BMD of 33 premenopausal Latina women age 22 to 51 years
      from Los Angeles, California were measured using dual-energy X-ray absorptiometry
      (DXA). Waist circumference (WC) was measured without clothing at the smallest
      circumference of the torso. Peak aerobic capacity (peak VO2) was determined by
      treadmill ergometry with direct measurement of oxygen consumption. RESULTS:
      Partial correlations controlling for total body fat mass, fat-free mass, and peak
      VO2 revealed a significant inverse relationship between BMC and WC (r = -0.54, P
      < 0.05) but not between BMD and WC (r = -0.18, P = 0.41). Similarly, while
      controlling for total body fat, fat-free mass, and peak VO2, BMC was inversely
      associated with trunk fat (r = -0.75, P < 0.001), with trunk lean (r = -0.61, P <
      0.05) and with total trunk weight (r = -0.75, P < 0.001); results were non
      significant for BMD. When these analyses were repeated separately in overweight
      (n = 10) versus in the obese (n = 18) women, inverse relationships between BMC
      and trunk fat as well as between BMC and total trunk weight became stronger in
      the obese compared with the overweight women. CONCLUSION: Although general
      obesity may prevent osteoporosis, these findings suggest that abdominal obesity
      (ie, trunk weight) specifically and independently may adversely influence bone
      mass.

PMID- 24665210
TI  - Abnormal bleeding during menopause hormone therapy: insights for clinical
      management.
AB  - OBJECTIVE: Our objective was to review the involved mechanisms and propose
      actions for controlling/treating abnormal uterine bleeding during climacteric
      hormone therapy. METHODS: A systemic search of the databases SciELO, MEDLINE, and
      Pubmed was performed for identifying relevant publications on normal endometrial
      bleeding, abnormal uterine bleeding, and hormone therapy bleeding. RESULTS:
      Before starting hormone therapy, it is essential to exclude any abnormal organic
      condition, identify women at higher risk for bleeding, and adapt the regimen to
      suit eachwoman's characteristics. Abnormal bleeding with progesterone/progestogen
      only, combined sequential, or combined continuous regimens may be corrected by
      changing the progestogen, adjusting the progestogen or estrogen/progestogen
      doses, or even switching the initial regimen to other formulation. CONCLUSION: To
      diminish the occurrence of abnormal bleeding during hormone therapy (HT), it is
      important to tailor the regimen to the needs of individual women and identify
      those with higher risk of bleeding. The use of new agents as adjuvant therapies
      for decreasing abnormal bleeding in women on HT awaits future studies.

PMID- 24665212
TI  - De materia medica versus codex alimentarius for the reinforcement of the
      gynecologic immune system: the case of endometriosis.
AB  - Since the first Pharmacopoeia under the title "De Materia Medica," the importance
      of the utilization of plants and herbs has been an invaluable medicinal tool
      successfully employed for strengthening the immune system for combating a number
      of diseases in general, or assisting fertility and reproductive issues in
      particular. The beneficial use of herbal extracts, constituting the basis of
      modern medicines, is lately under the shadow of Codex Alimentarius that
      threatens, if not properly applied, serious immunity features rendering the host
      defenseless for intercepting harmful invaders, one of which is the mesenchymal
      endometriotic stem cell causing endometriosis. 

PMID- 24665213
TI  - Efficacy and safety of remifentanil as an alternative labor analgesic.
AB  - The objective of this review was to evaluate the clinical efficacy and safety of
      remifentanil in the management of labor pain. Although neuraxial analgesia is the
      best option during labor, alternative analgesic options are needed for patients
      with contraindications. Using a systematic literature search, clinical outcomes
      of remifentanil for labor pain have been summarized. Also, comparisons of
      remifentanil to other options including meperidine, epidural analgesia, fentanyl,
      and nitrous oxide are provided. Based on the literature review, remifentanil is
      associated with high overall maternal satisfaction and favorable side-effect
      profile. However, due to the low reporting of adverse events, large, randomized
      controlled trials are needed to evaluate maternal and neonatal safety adequately
      and determine the optimal dosing needed to provide effective analgesia. While
      remifentanil is a feasible alternative for patients who cannot or do not want to
      receive epidural analgesia, administration should be monitored closely for
      potential adverse effects. 

PMID- 24665214
TI  - A new method for creating the bladder flap.
AB  - BACKGROUND: Bladder flaps are commonly created during routine cesarean deliveries
      and often require multiple steps that increase operating time and expose the
      surgeon to inadvertent injury. OBJECTIVE: We report a simple method of creating a
      bladder flap that eliminates the need for multiple instrument handoffs and
      repositioning. CONCLUSION: The simplicity of this method allows the surgeon
      decreased operative entry time while decreasing exposure to injuries from
      multiple instrument handoffs during bladder flap development.

PMID- 24665216
TI  - The Role of Vitamin D Supplements in Women's Health.
AB  - Vitamin D is pivotal to the absorption of calcium and maximizing bone health.
      Women suffer great morbidity and mortality related to osteoporosis and fractures,
      which may be decreased by interventions such as vitamin D. In addition,
      extraskeletal benefits of vitamin D have been postulated including positive
      effects on cancer. Both the classical and nonclassical functions of vitamin D
      will be discussed here, with a focus on women. 

PMID- 24665215
TI  - Effects of martial arts exercise on body composition, serum biomarkers and
      quality of life in overweight/obese premenopausal women: a pilot study.
AB  - Various exercise interventions have been shown to benefit weight control and
      general health in different populations. However, very few studies have been
      conducted on martial arts exercise (MAE). The objective of this pilot study is to
      evaluate the efficacy of 12 weeks of MAE intervention on body composition, serum
      biomarkers and quality of life (QOL) in overweight/obese premenopausal women. We
      found that subjects in the MAE group did not lose body weight, while they
      significantly decreased fat-free mass and muscle mass as compared to those in the
      control group, who demonstrated an increase in these parameters. The MAE group
      demonstrated an increase in serum IGF-I concentration, but no change in others.
      MAE may be a feasible and effective approach to improve body composition and QOL
      in overweight/obese premenopausal women. Our study underscores the need for
      further studies using larger samples to establish possible benefits of MAE in
      various populations. 

PMID- 24665217
TI  - Chemo-enzymatic Synthesis of Propionyl-ester-linked Taxol-monosaccharide
      Conjugate and its Drug Delivery System Using Hybrid-Bio-nanocapsules Targeting
      Brain Glioma Cells.
AB  - Taxol is recognized as one of the most potent anticancer agents used in the
      treatment of breast and ovarian cancers, which are common cancers in women. To
      overcome its shortcomings, that is, its low water-solubility that reduces drug
      loading capacity of DDS carriers when incorporating taxol, chemo-enzymatic
      synthesis of ester-linked taxol-glucose conjugate, i.e., 7-propionyltaxol 2"-O
      alpha-D-glucoside, as a water soluble taxol prodrug was achieved by using a
      glucosidase as a glucosylation catalyst. The water-solubility of 7-propionyltaxol
      2"-O-alpha-D-glucoside (25 mM) was 63 fold higher than that of taxol (0.4 mM).
      The pre-S1 peptide which displays on the surface of bio-nanocapsules, which are
      nanoparticles composed of the hepatitis B virus surface antigen, was replaced
      with the antibody affinity motif of protein A. Conjugation of such bio
      nanocapsules with anti-human epidermal growth factor receptor antibody gave
      hybrid bio-nanocapsules. The hybrid bio-nanocapsules were effective for
      delivering 7-propionyltaxol 2"-O-alpha-D-glucoside to human brain glioma cells. 7
      Propionyltaxol 2"-O-alpha-D-glucoside was effectively hydrolyzed to give taxol in
      95% by human glioma cells. The drug loading capacity of hybrid bio-nanocapsules
      incorporating 7-propionyltaxol 2"-O-alpha-D-glucoside was 120 times higher than
      that incorporating taxol itself. 

PMID- 24665218
TI  - Seven practical principles for improving patient education: Evidence-based ideas
      from cognition science.
AB  - An important role of the paediatrician is that of a teacher - every clinician is
      an educator to patients and their families. This education, however, often occurs
      under difficult or time-pressured learning conditions. The authors present
      principles derived from three basic theories of human cognition that may help to
      guide clinicians' instruction of parents and patients. Cognitive load theory
      holds that an individual's capacity to process information is finite. By
      controlling information flow rate, decreasing reliance on working memory and
      removing extraneous cognitive load, learning is improved. Dual code theory
      suggests that humans have separate cognitive 'channels' for text/audio
      information versus visual information. By constructing educational messages that
      take advantage of both channels simultaneously, information uptake may be
      improved. Multimedia theory is based on the notion that there is an optimal blend
      of media to accomplish a given learning objective. The authors suggest seven
      practical strategies that clinicians may use to improve patient education. 

PMID- 24665219
TI  - Case 2: A 20-month-old boy with asymmetric growth of the legs.

PMID- 24665220
TI  - Case 1: An infant with a low heart rate.

PMID- 24665221
TI  - Are salicylic formulations, liquid nitrogen or duct tape more effective than
      placebo for the treatment of warts in paediatric patients who present to
      ambulatory clinics?

PMID- 24665222
TI  - Outcome of patients with gastroschisis managed with and without multidisciplinary
      teams in Canada.
AB  - OBJECTIVE: To describe the outcomes of gastroschisis (GS) patients managed with
      and without a multidisciplinary team during the postoperative period in Canada.
      METHOD: The Canadian Pediatric Surgery Network (CAPSNet) collects patient data
      from all Canadian tertiary perinatal centres. The outcomes of 396 GS patients
      born between 2005 and 2009 who were managed with and without a multidisciplinary
      team were analyzed. RESULTS: Significantly more parenteral nutrition (PN) days
      (P=0.003) and longer lengths of stay (P=0.018) were observed among patients in
      centres with multidisciplinary teams. Higher mortality rate and earlier death
      were observed in centres without multidisciplinary teams, especially for high
      risk patients, although this was not statistically significant. With regard to
      low-risk patients, those in centres with multidisciplinary teams had
      significantly more PN days (P=0.019). CONCLUSIONS: GS patients managed by
      multidisciplinary teams had significantly more PN days and longer lengths of stay
      compared with patients who were not managed by multidisciplinary teams. This
      difference may be due to improved survival of high-risk patients in centres with
      multidisciplinary teams, and a uniform feeding approach for all patients.

PMID- 24665223
TI  - Implementation of the Canadian Paediatric Society's hyperbilirubinemia
      guidelines: A survey of Ontario hospitals.
AB  - INTRODUCTION: In 2007, the Canadian Paediatric Society (CPS) published guidelines
      aimed at preventing severe hyperbilirubinemia. OBJECTIVES: To determine whether
      hospitals had implemented these guidelines; to investigate how guideline
      recommended care is organized; and to understand the factors influencing
      guideline implementation. METHODS: The present study was an online survey
      conducted from December 2011 to May 2012 of all Ontario hospitals offering
      maternal-newborn services. RESULTS: A total of 97 of 100 eligible hospitals
      responded. Seventy-seven of the 97 (79%) respondents reported having implemented
      universal neonatal bilirubin screening. Among these hospitals, hospital-based
      postdischarge follow-up was reported more frequently than follow-up at community
      based locations: hospital laboratory (n=40 [52%]), mother-baby care unit (n=32
      [42%]), outpatient clinic (n=25 [33%]), primary care provider in community (n=19
      [25%]) and community laboratory (n=8 [10%]). The CPS guidelines were the most
      frequently reported factor influencing implementation (n=74 [96%]). DISCUSSION:
      The survey provides valuable insight into the impact of a complex guideline in
      Canada's largest province. There was heterogeneity in how hospitals organized
      services, but there was a notable trend toward hospital-based postdischarge care.
      The shift to hospital-based care runs counter to current health policy directions
      and highlights the lack of integration among health care sectors. CONCLUSION: The
      majority of Ontario hospitals implemented universal bilirubin screening following
      the release of the CPS guidelines. Further analysis is needed to determine the
      impact that the guidelines and the differences in implementation have had on
      clinical outcomes and the utilization of health services.

PMID- 24665224
TI  - Top 10 tips for effective use of electronic health records.

PMID- 24665225
TI  - Paediatric methadone ingestions: An under-recognized form of child maltreatment?

PMID- 24665226
TI  - Guidelines for the management of suspected and confirmed bacterial meningitis in
      Canadian children older than one month of age.
AB  - The incidence of bacterial meningitis in infants and children has decreased since
      the routine use of conjugated vaccines targeting Haemophilus influenzae type b,
      Streptococcus pneumoniae and Neisseria meningitidis. However, this infection
      continues to be associated with considerable mortality and morbidity if not
      treated effectively with empirical antimicrobial therapy. Diagnosis still rests
      on clinical signs and symptoms, and cerebrospinal fluid analysis. This position
      statement outlines the rationale for current recommended empirical therapy using
      a third-generation cephalosporin and vancomycin for suspected bacterial
      meningitis. It also provides new recommendations for the use of adjuvant
      corticosteroids in this setting. Once antibiotic susceptibilities of the pathogen
      are known, antimicrobials should be reviewed and modified accordingly.
      Recommendations for treatment duration as well as audiology testing are included.
      The present statement replaces a previous Canadian Paediatric Society position
      statement on bacterial meningitis published in 2007 and revised in 2008. 

PMID- 24665227
TI  - Sport-related concussion: Evaluation and management.
AB  - Concussion is a common injury among children and adolescents participating in
      organized sports and recreational activities. Any child or youth who sustains a
      concussion should be removed from play immediately and medically evaluated as
      soon as possible. Cognitive and physical rest are recommended to allow symptoms
      to resolve. Cognitive rest may require temporary school absence and/or a modified
      class work or homework load. After symptoms have completely resolved at rest and
      a full return to school is achieved, the student can progress through a medically
      supervised, stepwise exertion protocol to return to play. Everyone involved in
      child and youth sports must recognize the signs and symptoms of concussion, and
      ensure that any child or adolescent suspected of sustaining a concussion is
      properly evaluated and managed by qualified medical personnel. The present
      statement replaces a previous Canadian Paediatric Society position statement
      published in 2006 and revised in 2012. 

PMID- 24665228
TI  - Prevalence of vitamin D insufficiency among healthy school-age Cree children.
AB  - BACKGROUND: First Nations children are at higher risk for vitamin D deficiency
      and rickets. OBJECTIVE: To assess the prevalence of vitamin D deficiency and the
      correlations between fat mass, parathyroid hormone and dietary habits with serum
      vitamin D level in a random sample of Cree children eight to 14 years of age.
      METHODS: Serum 25-hydroxyvitamin D (25[OH]D) levels and additional information
      regarding anthropometrics and dietary habits were obtained from participants in
      two Cree communities. Vitamin D deficiency and insufficiency was defined as serum
      25(OH)D levels <30 nmol/L and <50 nmol/L, respectively. Proportions to estimate
      the vitamin D status were weighted to account for the complex sampling design,
      and Pearson's correlation coefficients were used to estimate the associations of
      milk and fish intake, parathyroid hormone and fat mass with serum 25(OH)D levels.
      RESULTS: Data from 52 healthy Cree children (mean [+/- SD] age 11.1+/-2.0 years;
      27 boys) were included in the analyses. The median serum 25(OH)D level was 52.4
      nmol/L (range 22.1 nmol/L to 102.7 nmol/L). Forty-three percent (95% CI 29% to
      58%) and 81% (95% CI 70% to 92%) of Cree children had vitamin D levels <50 nmol/L
      and <75 nmol/L, respectively. Vitamin D intake was positively associated with
      serum 25(OH)D levels. Obese children had lower vitamin D levels; however, the
      difference was nonsignificant. CONCLUSION: There may be a substantial proportion
      of Cree children who are vitamin D deficient. Increasing age, lower dietary
      vitamin D intake and, possibly, higher body mass index were associated with
      decreased vitamin D levels; however, causality cannot be inferred.

PMID- 24665229
TI  - Identification of the need for home visiting nurse: development of a new
      assessment tool.
AB  - OBJECTIVE: To develop a Home Visiting Nursing Service Need Assessment Form (HVNS
      NAF) to standardize the decision about the need for home visiting nursing
      service. METHODS: The sample consisted of older adults who had received
      coordinated services by care managers. We defined the need for home visiting
      nursing service by elderly individuals as the decision of the need by a care
      manager so that the elderly can continue to live independently. Explanatory
      variables included demographic factors, medical procedure, severity of illness,
      and caregiver variables. Multiple logistic regression was carried out after
      univariate analyses to decide the variables to include and the weight of each
      variable in the HVNS-NAF. We then calculated the sensitivity and specificity of
      each cutoff value, and defined the score with the highest sensitivity and
      specificity as the cutoff value. RESULTS: Nineteen items were included in the
      final HVNS-NAF. When the cutoff value was 2 points, the sensitivity was 77.0%,
      specificity 68.5%, and positive predictive value 56.8%. CONCLUSIONS: HVNS-NAF is
      the first validated standard based on characteristics of elderly clients who
      required home visiting nursing service. Using the HVNS-NAF may result in reducing
      the unmet need for home visiting nursing service and preventing hospitalization.

PMID- 24665230
TI  - Endocrine anesthesia: A rapidly evolving anesthesia specialty.

PMID- 24665231
TI  - A deeper understanding of anesthesiology practice: the biopsychosocial
      perspective.

PMID- 24665232
TI  - Low-dose ketamine infusion for labor analgesia: A double-blind, randomized,
      placebo controlled clinical trial.
AB  - BACKGROUND: Most primary and secondary level hospitals in developing countries
      provide inadequate labor analgesia due to various medical, technical and economic
      reasons. This clinical trial was an effort to study the efficacy, safety and
      feasibility of intravenous (IV) ketamine to provide labor analgesia. MATERIALS
      AND METHODS: A total of 70 parturients were consented and randomly assigned to
      receive either IV ketamine or 0.9% saline. A loading dose of ketamine (0.2 mg/kg)
      was followed-by an infusion (0.2 mg/kg/h) until the delivery of the neonate.
      Similar volume of saline was infused in the placebo-group. Intramuscular
      meperidine was the rescue analgesic in both groups. The pain score, hemodynamic
      parameters of mother and fetus and the anticipated side-effects of ketamine were
      observed for. The newborn was assessed by the Neonatologist. RESULTS: The pain
      score showed a decreasing trend in the ketamine group and after the 1(st) h more
      than 60% of women in the ketamine group had pain relief, which was statistically
      significant. There was no significant clinical change in the maternal
      hemodynamics and fetal heart rate. However, 17 (48.5%) of them had transient
      light headedness in the ketamine group. All the neonates were breast fed and the
      umbilical cord blood pH was between 7.1 and 7.2. The overall satisfaction was
      significantly high in the intervention group (P = 0.028). CONCLUSION: A low-dose
      ketamine infusion (loading dose of 0.2 mg/kg delivered over 30 min, followed-by
      an infusion at 0.2 mg/kg/h) could provide acceptable analgesia during labor and
      delivery.

PMID- 24665233
TI  - Use of oral tramadol to prevent perianesthetic shivering in patients undergoing
      transurethral resection of prostate under subarachnoid blockade.
AB  - CONTEXT: Under regional anesthesia, geriatric patients are prone to shivering
      induced perioperative complications that Anesthesiologists should prevent rather
      than treat. AIM: We investigated the prophylactic efficacy of oral tramadol 50 mg
      to prevent the perioperative shivering after transurethral resection of prostate
      (TURP) surgery under subarachnoid blockade (SAB). Shivering is usually overlooked
      in patients undergoing urological surgery under spinal anesthesia and may result
      in morbidity, prolonged hospital stay and increased financial burden. Use of
      prophylactic measures to reduce shivering in geriatric patients who undergo
      urological procedures could circumvent this. Oral formulation of tramadol is a
      universally available cost-effective drug with the minimal side-effects. SETTINGS
      AND DESIGN: Prospective, randomized, double-blinded, placebo-controlled study.
      PATIENTS AND METHODS: A total of 80 patients who were scheduled for TURP surgery
      under subarachnoid block were randomly selected. Group I and II (n = 40 each)
      received oral tramadol 50 mg and placebo tablet respectively. After achieving
      subarachnoid block, the shivering, body temperature (tympanic membrane, axillary
      and forehead), hemodynamic parameters and arterial saturation were recorded at
      regular intervals. STATISTICAL ANALYSIS USED: T-test, analysis of variance test,
      Z-test and Fisher exact test were utilized while Statistical Product and Service
      Solutions, IBM, Chicago (SPSS statistics (version 16.0)), software was used for
      analysis. RESULTS: Incidence of shivering was significantly less in patients who
      received tramadol (7.5% vs. 40%; P < 0.01). The use of tramadol was associated
      with clinically inconsequential side-effects. CONCLUSION: We conclude that the
      use of oral tramadol 50 mg is effective as a prophylactic agent to reduce the
      incidence, severity and duration of perioperative shivering in patients
      undergoing TURP surgery under SAB.

PMID- 24665234
TI  - Comparison of nasal Midazolam with Ketamine versus nasal Midazolam as a
      premedication in children.
AB  - BACKGROUND: This study was done to compare effects of intranasal midazolam and
      intranasal midazolam with ketamine for premedication of children aged 1-12 yrs
      undergoing intermediate and major surgeries. AIMS: Midazolam and Ketamine have
      already been used as premedicants in children. Our aim was to find out advantage
      of combination of midazolam with ketamine over midazolam by nasal route. METHODS:
      Sixty children of age group 1-12 yrs of American Society of Anesthesiologists
      (ASA) grade 1 and 2 were selected. Group A- midazolam (0.2 mg/kg), Group B-
      midazolam (0.15 mg/kg + ketamine 1 mg/kg). Both groups received drug intranasally
      30 min before surgery in recovery room with monitored anesthesia care. Onset of
      sedation, sedation score, emotional reaction, intravenous cannula acceptance, and
      mask acceptance were studied. STATISTICAL ANALYSIS: Unpaired t test and chi
      square test. RESULTS: Sedation score, anxiolysis, attitude, reaction to
      intravenous cannulation, face mask acceptance, and emotional reaction were
      significantly better in midazolam with ketamine group. Intra operatively, in both
      groups, pulse rate, oxygen saturation, and respiratory rate had no significant
      difference; also, post operatively, no significant difference was observed in
      above parameters, post operative analgesia was significantly better in midazolam
      with ketamine group. CONCLUSIONS: Intra nasal premedication allows rapid and
      predictable sedation in children. Midazolam as well as combination of Midazolam
      with ketamine gives good level of sedation and comfort. But quality of sedation,
      analgesia, and comfort is significantly better in midazolam with ketamine group.
      No significant side effects were observed in both groups.

PMID- 24665235
TI  - Albumin and fibrinogen levels' relation with orthopedics traumatic patients'
      outcome after massive transfusion.
AB  - BACKGROUND: Severe bleeding is common during limb trauma. It can lead to
      hemorrhagic shock required to massive blood transfusion. Coagulopathy is the
      major complication of massive transfusion-induced increased mortality rate. Aim
      of this study was evaluation of fibrinogen and albumin levels association with
      orthopedics traumatic patients' outcome who received massive transfusion.
      METHODS: In a cross sectional study, 23 patients with severe limb injury admitted
      to orthopedic emergency department were studied. All the patients received
      massive transfusion, that is, >10 unit blood. Albumin and fibrinogen levels are
      measured at admission and 24 h later, and compared according to final outcome.
      RESULTS: Twenty-three traumatic patients with severe limb injuries were studied,
      out of which ten (43.2%) died and 13 (56.8%) were alive. There was significant
      difference between patients outcome in fibrinogen level after 24 h, but no
      difference was observed in albumin levels. Based on regression model, fibrinogen
      after 24 h had a significant role in determining the final outcome in traumatic
      patients who received massive transfusion (odds ratio 0.48, 95% confidence
      interval 0.15-0.92, P = 0.02). CONCLUSIONS: According to our results, fibrinogen
      level is the most important factor in determination of orthopedics traumatic
      patients when received massive transfusion. However, serum albumin does not play
      any role in patients' outcome.

PMID- 24665236
TI  - PONV in Ambulatory surgery: A comparison between Ramosetron and Ondansetron: a
      prospective, double-blinded, and randomized controlled study.
AB  - BACKGROUND: postoperative nausea and vomiting (PONV) frequently hampers
      implementation of ambulatory surgery in spite of so many antiemetic drugs and
      regimens. AIMS: the study was carried out to compare the efficacy of Ramosetron
      and Ondansetron in preventing PONV after ambulatory surgery. SETTING AND DESIGN:
      it was a prospective, double blinded, and randomized controlled study. METHODS:
      124 adult patients of either sex, aged 25-55, of ASA physical status I and II,
      scheduled for day care surgery, were randomly allocated into Group A [(n=62)
      receiving (IV) Ondansetron (4 mg)] and Group B [(n=62) receiving IV Ramosetron
      (0.3 mg)] prior to the induction of general anesthesia in a double-blind manner.
      Episodes of PONV were noted at 0.5, 1, 2, 4 h, 6, 12, and 18 h postoperatively.
      STATISTICAL ANALYSIS AND RESULTS: statistically significant difference between
      Groups A and B (P <0.05) was found showing that Ramosetron was superior to
      Ondansetron as antiemetic both regarding frequency and severity. CONCLUSION: it
      was evident that preoperative prophylactic administration of single dose IV
      Ramosetron (0.3 mg) has better efficacy than single dose IV Ondansetron (4 mg) in
      reducing the episodes of PONV over 18 h postoperatively in patients undergoing
      day-care surgery under general anesthesia.

PMID- 24665237
TI  - A comparison between over-the-head and lateral cardiopulmonary resuscitation with
      a single rescuer by bag-valve mask.
AB  - CONTEXT: mask fixation in the lateral position is difficult during CPR. AIM: the
      aim of this study is to compare the lateral CPR for the use of bag-valve mask by
      single paramedic rescuer as well as over-the-head CPR on the chest compression
      and ventilation on the manikin. SETTINGS AND DESIGN: Mazandaran University of
      Medical Sciences. The design of this study was a randomized cross-over trial.
      METHODS: participants learned a standardized theoretical introduction CPR
      according to the 2010 guidelines. The total number of chest compressions per two
      minutes was measured. Total number of correct and wrong ventilation per two
      minutes was evaluated. STATISTICAL ANALYSIS: we used Wilcoxon signed-rank test to
      analyze the non-normally distributed data in dependence groups A. P-value of more
      than 0.05 was considered to show statistical significance. RESULTS: there were
      100 participants (45 women and 55 men) who participated in the study from
      September to March, 2011. The compression and ventilation rate in lateral CPR was
      lower than OTH CPR. Around 51% of participants had correct chest compression rate
      more than 90 beats per minute in lateral CPR and 65% of them had equal or more
      than ten correct ventilations per minute. CONCLUSIONS: in conclusion, this study
      confirmed that in a simulated CPR model over-the-head position CPR led to a
      better BLS than the lateral position CPR by a single paramedic student with a BVM
      device. We also concluded that by this new BVM fixation method on the face of the
      patients in the lateral position CPR can be a good alternative over-the-head mask
      fixation by a single trained rescuer.

PMID- 24665238
TI  - Lornoxicam versus tramadol for post-operative pain relief in patients undergoing
      ENT procedures.
AB  - BACKGROUND: Pain following ear-nose and throat surgery is one of the most
      important complaints for which, several drugs are used. This prospective,
      randomized, double-blind controlled trial was designed to compare the analgesic
      effect of tramadol versus lornoxicam for post-operative pain relief in patients
      undergoing ENT surgical procedures. METHODS: One hundred and twenty patients of
      ASA class I-II, who had undergone elective ENT surgical procedures under general
      anesthesia, were assigned in a randomized manner into three equal groups. Group L
      received lornoxicam8 mg IV, Group T received tramadol 1 mg/kg IV and Group C
      received IV saline after induction of anesthesia before the start of the surgery.
      Post-operative pain was assessed using the visual analogue scale (VAS) and
      sedation level was evaluated during stay in the post-anesthesia care unit with a
      four-point sedation scale. Intraoperative blood loss was estimated using the Five
      Point Scale. Adverse events in the first 24 h post-operative were recorded.
      RESULTS: The VAS pain scores were significantly higher in Group C as compared
      with those in Groups L and T at 30 min and 1, 2, 4and 6 h post-operatively, with
      no significant difference between Group L and Group T. The amount of morphine
      consumption post-operatively was significantly lower in Group L (5.2 +/- 2.5 mg)
      and Group T (5.0 +/- 2.0 mg) as compared with that in Group C (7.4 +/- 2.3 mg) (P
      = 0.001). The time for the first analgesic requirement was significantly less in
      Group L (92.62 +/- 24.23 min) and Group T (88 +/- 21.43 min) as compared with
      that in Group C (42.82 +/- 25.61 min), with no significant difference between the
      other two groups. Estimated intraoperative blood loss score by the surgeons
      showed no significant difference between the three groups. The most frequent side
      effects in the three groups were nausea and vomiting, and their incidence was
      significantly higher in the placebo group as compared with the other two groups.
      CONCLUSION: Tramadol 1 mg/kg was comparable to lornoxicam 8 mg for post-operative
      pain relief in patients undergoing ENT surgical procedures; both drugs helped to
      reduce the post-operative opioid requirement and consequently minimized the
      related adverse effects of the opioids.

PMID- 24665239
TI  - Ring block with levobupivacaine 0.25% and paracetamol vs. paracetamol alone in
      children submitted to three different surgical techniques of circumcision: A
      prospective randomized study.
AB  - BACKGROUND: circumcision in children is a painful procedure. We aim compare the
      intraoperative and postoperative efficacy of three different surgical procedures
      of the ring block using levobupivacaine 0.25% combined with rectal paracetamol as
      opposed to rectal paracetamol alone. METHODS: the study included 106 boys
      scheduled to undergo circumcision. The patients were randomly assigned within two
      groups to receive either ring block with levobupivacaine 0.25% and rectal
      paracetamol 30 mg/kg, or rectal paracetamol 30 mg/kg alone. The following
      surgical procedures were performed: sutureless proctoplasty, preputial plasty,
      and conventional circumcision. The efficacy of intraoperative analgesia was
      estimated on the basis of increases in heart rate and mean arterial pressure.
      Postoperatively, children were assessed for pain, pain-free (PF) period, and the
      total doses of analgesics administered during hospitalization, on the day after
      discharge, and on the first and second postoperative days. RESULTS: all children
      remained stable during anesthesia. Postoperatively, the mean pain score did not
      show statistical differences between the groups. Children who received combined
      analgesia had a longer PF period (P < 0.001). However, the total doses of
      paracetamol administered during the observational period showed no differences.
      Children undergoing sutureless prepuceplasty received lower doses of paracetamol
      postoperatively (P < 0.001). CONCLUSION: subcutaneous ring block either with
      levobupivacaine 0.25% plus rectal paracetamol or rectal paracetamol alone
      provides adequate intraoperative and postoperative analgesia in circumcised
      children. However, combined analgesia allows a longer PF period. The need for
      less analgesic administration in children undergoing sutureless prepuceplasty
      could mean that the circumcision techniques might be a mitigating factor in terms
      of pain.

PMID- 24665240
TI  - A comparison of the analgesic efficacy of transforaminal methylprednisolone alone
      and with low doses of clonidine in lumbo-sacral radiculopathy.
AB  - BACKGROUND: Although transforaminal epidural steroid injections under
      fluoroscopic guidance have become a common mode of treatment of lumbosacral
      radiculopathy due to herniated disc, the efficacy of steroid with low doses of
      clonidine has not been compared yet. OBJECTIVES: Comparison of the analgesic
      efficacy of methylprednisolone alone and with low doses of clonidine for
      transforaminal injection in lumbosacral radiculopathy. STUDY DESIGN: A
      randomized, double-blind trial. SETTING: This study was performed at the Pain
      Clinic under the Department of Anaesthesiology, Jawaharlal Nehru Medical College
      Hospital, Aligarh Muslim University, Aligarh, India. METHODS: One hundred and
      eighty ASA grade I and II patients aged between 18 and 55 years were allocated
      into groups I, II and III to receive methylprednisolone 60 mg alone or
      methylprednisolone 60 mg with or without low doses of clonidine (0.5 mcg/kg or 1
      mcg/kg) as transforaminal epidural injection. Pain relief and patient's
      satisfaction were evaluated with the global pain scale. Follow-up visits were
      advised at 1, 2, 4, 6 and 12 weeks and then at 6 months after injection.
      Associated complications were recorded. RESULTS: Maximum pain relief was observed
      at 2 weeks after injection in all the three groups, with no difference in
      complication rate among the three groups. The most common complication observed
      was paresthesia in the nerve distribution. Greater than 60% improvement in pain
      scores was seen in 40% of the patients in group I, 50% of the patients in group
      II and 75% of the patients in group III. LIMITATIONS: This study is limited by
      the lack of a placebo group. CONCLUSION: Adding 1 mcg/kg clonidine to 60 mg
      methylprednisolone in transforaminal epidural injections provided better pain
      relief than 60 mg methylprednisolone with 0.5 mcg/kg clonidine or 60 mg
      methylprednisolone alone in patients suffering from lumbosacral radiculopathy,
      with practically no significant side-effects.

PMID- 24665241
TI  - A randomized clinical trial comparing the efficacy and safety of ramosetron
      versus ondansetron in patients undergoing abdominal surgery under general
      anesthesia.
AB  - BACKGROUND: Post-operative nausea and vomiting is one of the most common and
      distressing complications after anesthesia and surgery. It may lead to serious
      post-operative complications. Ramosetron is a newer 5-HT3 receptor antagonist and
      has more potent and longer duration of antiemetic effects compared to first
      generation 5HT3 receptor antagonists. The purpose of this study was to compare
      the efficacy of Ramosetron for the prevention of post-operative nausea and
      vomiting with that of Ondansetron in patients undergoing abdominal surgeries
      under general anesthesia. METHODS: In this randomized, double-blind study, 60
      patients, 18-60 years of both genders falling under ASA I-II category scheduled
      for abdominal surgery were included. Group I received I.V ramosetron 0.3 mg while
      group II received I.V Ondansetron 4 mg at the time of extubation. The standard
      general anesthetic technique was used throughout. Postoperatively the incidences
      of nausea, vomiting, and safety assessments were performed at 1, 2, 6, and 24 h
      during the first 24 h after surgery. RESULTS: There were no differences between
      groups with respect to patient demographics. The percentage of patients who had
      complete response (no PONV, and no need for another rescue antiemetic) from 0 to
      24 h after anesthesia was 56% with ramosetron and 33% with ondansetron. The
      corresponding rates at 1, 2, 6, and 24 h after anesthesia were 76% and 63%, 76%
      and 50%, 100 and 83%, 100 and 93%, respectively. Safety profiles of the two drugs
      were comparable, as no clinically serious adverse effects caused by study drugs
      were observed in either of the groups. CONCLUSION: Our study concludes that
      prophylactic therapy with ramosetron is highly efficacious than ondansetron in
      preventing PONV in patients undergoing abdominal surgery under general
      anesthesia.

PMID- 24665242
TI  - Intrathecal fentanyl as an adjuvant to 0.75% isobaric ropivacaine for
      infraumbilical surgery under subarachnoid block: A prospective study.
AB  - BACKGROUND: Subarachnoid blockade can be used in all surgical procedures carried
      out on the infraumbilical region. This study was aimed to evaluate the clinical
      efficacy and safety of intrathecal fentanyl as an adjuvant to 0.75% isobaric
      ropivacaine on onset, duration, intensity, and recovery time of sensory and motor
      blockade of subarachnoid block for infra umbilical surgery. METHODS: One hundred
      sixty adult consented patients of either gender with American Society of
      Anesthesiologist ASA I and II scheduled for infraumbilical surgery were
      randomized into two groups of 80 patients each to receive either intrathecal
      study solution of 4 mL of 0.75% ropivacaine with 0.4 mL of 0.9% sodium chloride
      (Group I-Ropivacaine Control Group RC) or fentanyl (20 MUg) (Group II-Ropivacaine
      with Fentanyl RF). The end points were hemodynamic variability, onset of
      analgesia at T 10, maximum sensory analgesic level, time to complete motor
      blockade, duration of sensory and motor blockade and adequacy of surgical
      anesthesia. The post-spinal nausea and vomiting, shivering, pruritus, respiratory
      depression or any other side-effects were also assessed. At the end of study,
      data were systematically complied and analyzed for statistically significance.
      RESULT: The intrathecal fentanyl has accelerated the onset time to achieve
      sensory blockade to T10 dermatome and motor blockade. Small dose of intrathecal
      fentanyl with ropivacaine has prolonged the duration of analgesia in the early
      post-operative period when compared with intrathecal ropivacaine alone. The
      intraoperative hemodynamic variability showed no statistically significant
      differences between groups. CONCLUSION: Intrathecal fentanyl as an adjuvant to
      0.75% isobaric ropivacaine demonstrated better clinical profile as compared to
      ropivacaine alone.

PMID- 24665243
TI  - Effect of auditory stimulation on traumatic coma duration in intensive care unit
      of Medical Sciences University of Mazandarn, Iran.
AB  - BACKGROUND: Sensory deprivation is one of the common complications of coma
      patients in the intensive care unit (ICU). The purpose of this study was to
      investigate the impact of a familiar voice to consciousness level in coma
      patients. METHODS: A total of 13 patients with traumatic coma (8 >= Glasgow's
      coma scale [GCS]) admitted in ICU ward were randomly assigned to control and
      experimental groups. The experimental group was treated twice a daily each time
      15 min with a familiar recorded MP3 sound for 2 weeks. The control group received
      only natural voices of environment. GCS applied to evaluate patients' level of
      consciousness. FINDING: Findings showed that duration to reach GCS = 15 was
      significantly shorter in the experimental group (chi(2) = 12/96, P < 0/001).
      CONCLUSION: These findings imply that providing familiar auditory stimulation
      programs for coma patients in the ICU could be effective.

PMID- 24665244
TI  - Application of the upper lip catch test for airway evaluation in edentulous
      patients: An observational study.
AB  - BACKGROUND: Application of upper lip catch test (ULCT) for airway evaluation in
      edentulous patients. METHODS: This research is an evaluation of a clinical
      diagnostic test in edentulous patients prior to operation. Five hundred eighty
      eight edentulous patients in a referral university hospital, between March 2008
      and June 2011 scheduled for elective surgery under general anesthesia were
      enrolled. Those unable to open the mouth and those with pharyngo-laryngeal
      pathology were excluded. ULCT was assessed and compared with Cormack-Lehane
      grading as a gold standard for airway evaluation. RESULTS: A high negative
      predictive value of 99.4% was a notable finding for the ULCT. The results also
      showed a high specificity (89.4%), high sensitivity (75.0%) and a high accuracy
      (89.3%) in a comparatively higher range for the ULCT. CONCLUSION: The ULCT proved
      to be a useful predictor for airway assessment in edentulous patients in this
      setting. Further studies are needed to reconfirm its validity in other ethnic
      groups.

PMID- 24665245
TI  - Effect of continuous magnesium sulfate infusion on spinal block characteristics:
      A prospective study.
AB  - BACKGROUND: Spinal anesthesia is an established mode of anesthesia for lower limb
      orthopedic surgeries. The limitations of the technique are short duration of
      action and limited post-operative analgesia. Concomitant use of intravenous
      infusion of magnesium sulfate may have an effect on the block characteristics and
      duration of action of intrathecal bupivacaine. METHODS: A total of 80 American
      Society of Anesthesiologists I and II patients, either sex, 20-60 years of age
      scheduled for elective orthopedic fixation of fracture of long bones of lower
      limbs under spinal anesthesia were included. Spinal anesthesia administered with
      2.5 ml heavy bupivacaine mixed with 10 mcg fentanyl. The groups were then divided
      to receive an infusion of injection magnesium sulfate 50 mg/kg/h over 15 min
      followed by 15 mg/kg/h until the end of the surgery (Group M) and 15 ml of Normal
      Saline over 15 min followed by 100 ml/h until the end of surgery (Group S).
      Onset, duration of sensory and motor block and amount of post-operative analgesic
      were noted. RESULTS: A total of 6 patients (Group M) and seven patients (Group S)
      had inadequate block and excluded from the study. Mean block height was T6. Time
      required to achieve block height was 8.82 min versus 7.42 min in Groups M and S
      respectively (P = 0.04). Mean duration of motor block was longer in group M
      (160.63 +/- 17.76 min) compared with Group S (130.12 +/- 20.70 min) (P = 0.000).
      Time for regression of sensory block to T12/L1was 206.88 +/- 20.96 min (Group M)
      and 163.88 +/- 15.46 min (Group S) (P = 0.000). Hemodynamic parameters were
      similar and statistically not significant. Need for first analgesic requirement
      was after 262.88 +/- 21.11 min in group M and 193.25 +/- 17.74 min in the group S
      (P = 0.000). Mean dosage of tramadol needed in first 24 h was less in group M
      (190 +/- 30.38 mg vs. 265 +/- 48.30 mg, P = 0.000). CONCLUSION: Use of
      intravenous magnesium with spinal anesthesia reduces post-operative pain and
      analgesic consumption.

PMID- 24665246
TI  - A comparison of granisetron and nitroglycerine for attenuating rocuronium pain: A
      double-blinded randomized, placebo controlled trial.
AB  - BACKGROUND: The incidence of pain reported in literature after IV administration
      of rocuronium is 50-80%. The aim of our study was to determine whether pre
      treatment with intravenous granisetron and nitroglycerine would reduce rocuronium
      induced pain. METHODS: One hundred fifty patients of either sex, aged 18-65
      years, American society of Anaesthesiologist grading (ASA) I-II, scheduled for
      various surgeries under general anesthesia were randomly assigned to one of the
      groups. Group G: received 2 granisetron (1mg/ml) diluted with 3 ml of 0.9% normal
      saline) while the Group C: received 5 ml of 0.9% normal saline. Group N: received
      200?g of nitroglycerine diluted to a total of 5 ml(with 0.9% normal saline). It
      was accompanied by manual venous occlusion for 20 seconds. Then 0.06mg/kg of
      rocuronium was injected through same cannula over 10-15 sec. Patients were asked
      by a blinded investigator to score the pain on injection of rocuronium using
      visual analogue scale (0-10) with 0-no pain,1-3 mild pain, 4-6 moderate and >=7
      severe pain. At the same time discomfort in the form of patient's movement, such
      as no movement (grade 0), movement only wrist (grade 1), movement to the upper
      arm and shoulder of injected arm (grade 2) or generalized movements (grade3) was
      observed. Statistical analysis using independent t test, Mann-Whitney test and
      reverse ANOVA was done. RESULTS: 1. At 0 seconds, in group G number of patients
      who experienced withdrawl score of 0-1 were 92%,group N were 82% while only 26%
      of patients in group C had favourable withdrawl score.74% of patients in group C
      had score of 2-3 at same time. 2. At 0 sec, in group G number of patients who
      experienced VAS score of 0-3 were 96%, group N 72%. At same time Group C 48 % of
      patients had VAS score of 2-3. CONCLUSION: We conclude that pre-treatment with
      granisetron or nitroglycerine both are highly effective in attenuation of
      rocuronium induced pain.

PMID- 24665247
TI  - Efficacy of spinal ropivacaine versus ropivacaine with fentanyl in transurethral
      resection operations.
AB  - BACKGROUND: The low-dose ropivacaine provides differential spinal block to reduce
      adverse hemodynamic effects in elderly patients. Addition of intrathecal fentanyl
      with ropivacaine may enhance analgesia and early postoperative mobility. The
      present study was performed to evaluate the efficacy of intrathecal ropivacaine
      alone and in combination with fentanyl in transurethral resection operation.
      METHODS: Sixty male patients aged >50 years of ASA I-III scheduled for elective
      transurethral resection were included in a prospective, randomized, double
      blinded study and they were divided in two groups of 30 each. Group A (n = 30)
      received intrathecal injection of ropivacaine 2 ml (0.75%) and Group B (n = 30)
      ropivacaine 1.8 ml (0.75%) with fentanyl 10 MUg. The characteristics of onset and
      regression of sensory and motor blockade, hemodynamic stability, and side effects
      were observed. Student's t test (for parametric data) and Mann-Whitney U test
      (for non-parametric data) were used for statistical analyses. RESULTS: There were
      no significant differences between the two groups for patient demographic data,
      intraoperative hemodynamic parameters, side effects, and satisfaction to patients
      and surgeon. The highest level of sensory block was at T10 in group A and T9 in
      group B (P = 0.001). Duration of motor block was longer in group B being 210.51
      +/- 61.25 min than in group A being 286.25 +/- 55.65 min (P < 0.001). CONCLUSION:
      The addition of fentanyl to ropivacaine may offer the advantage of shorter
      duration of complete motor block, hemodynamic stability, and without any increase
      in the frequency of major side effects.

PMID- 24665248
TI  - Clonidine for management of chronic pain: A brief review of the current
      evidences.
AB  - Clonidine, an alpha-2 adrenergic receptor agonist, has well-established role in
      acute perioperative pain management. However, recently it has found increasing
      use in chronic pain conditions as well. In this review, we systematically
      searched and analyzed the clinical studies from "PubMed," "PubMed central" and
      "Scopus" database for use of clonidine in the chronic pain. Quantitative meta
      analysis was not possible as clonidine has been used in various patient
      populations through different routes. However, qualitative analysis of nearly
      thirty clinical studies provides some evidence that clonidine administered
      through epidural, intrathecal and local/topical route may be effective in chronic
      pain conditions where neuropathy is a predominant component. It may also be
      effective where opioids are of limited use due to inadequate pain relief or
      adverse effects. 

PMID- 24665249
TI  - Anesthetic management of descending thoracic aortobifemoral bypass for aortoiliac
      occlusive disease: Our experience.
AB  - BACKGROUND: Complete obstruction of the abdominal aorta at the renal artery level
      is a difficult surgical problem. Aortic clamping and declamping can lead to
      profound haemodynamic changes, myocardial infarction, ventricular failure or even
      death may result. These complications are important challenges in anesthetic
      management of these patients. METHODS: Between August, 2010 and April, 2012,
      descending thoracic aorta to femoral artery bypass grafting was used to
      revascularize lower limbs in 11 patients in our institute. The anesthetic
      management of these patients is described here. Epidural catheter placement was
      done in T 5-6 or T 6-7 space for post operative pain relief. Induction was done
      by, Inj. Glycopyrolate 0.2 mg, Inj. Fentanyl 5 MUg/kg., Inj. Pentothal sodium 5
      mg/kg, Inj. Rocuronium 0.9 mg/kg, IPPV done. Left sided double lumen tube was
      inserted, Maintenance of Anesthesia was done by O2 + N2 O (30:70). Increments of
      Vecuronium and Fentanyl were given Monitoring of Heart rate, arterial pressure,
      central venous pressure were continuously displayed. The available
      pharmacological agents were used when there is deviation of more than 15% from
      base line. RESULTS: In our study, inspite of measures taken to control rise in
      blood pressure during aortic cross clamping, a rise of 90 mm of Hg in one patient
      and 60-80 mm of Hg in four patients was observed, which was managed by sodium
      nitropruside infusion. At the end of surgery seven patients were extubated on the
      operation table. In remaining four patients DLT was replaced by single lumen
      endotracheal tube and were shifted to ICU on IPPV. They weaned off gradually in 3
      5 hours. In our series blood loss was 400 ml to 1000 ml. There was no mortality
      in the first 24 hours. Postoperative bleeding was reported in one case which was
      re-explored and stood well. CONCLUSION: The anesthetic technique during aortic
      surgery is directed at minimizing the hemodynamic effects of cross clamping in
      order to maintain the myocardial oxygen supply demand ratio.

PMID- 24665250
TI  - When place and time matter: How to conduct safe inter-hospital transfer of
      patients.
AB  - Inter-hospital transfer (IHT) of patients is often needed for diagnostic or
      therapeutic interventions. However, the transfer process carries its own risks as
      a poorly and hastily conducted transfer could lead to adverse events. In this
      article, we have reviewed literature on the key elements of IHT process including
      pre-transfer patient stabilization. We have also discussed various modes of
      transfer, physiological effects of transfer, possible adverse events and how to
      avoid or mitigate these. Even critically ill-patients can be transported safely
      by experienced and trained personnel using appropriate equipment. The patient
      must be maximally stabilized prior to transfer though complete optimization may
      be possible only at the receiving hospital. Ground or air transport may be
      employed depending on the urgency, feasibility and availability. Meticulous pre
      transfer check and adherence to standard protocols during the transfer will help
      keep the entire process smooth and event free. The transport team should be
      trained to anticipate and manage any possible adverse events, medical or
      technical, during the transfer. Coordination between the referring and receiving
      hospitals would facilitate prompt transfer to the definitive destination avoiding
      delay at the emergency or casualty. Documentation of the transfer process and
      transfer of medical record and investigation reports are important for
      maintaining continuity of medical care and for medico-legal purposes. 

PMID- 24665251
TI  - Pre-hospital and initial management of head injury patients: An update.
AB  - BACKGROUND: Most of the bad outcomes in patients with severe traumatic brain
      injury (TBI) are related to the presence of a high incidence of pre-hospital
      secondary brain insults. Therefore, knowledge of these variables and timely
      management of the disease at the pre-hospital period can significantly improve
      the outcome and decrease the mortality. The Brain Trauma Foundation guideline on
      "Prehospital Management" published in 2008 could provide the standardized
      protocols for the management of patients with TBI; however, this guideline has
      included the relevant papers up to 2006. METHODS: A PubMed search for relevant
      clinical trials and reviews (from 1 January 2007 to 31 March 2013), which
      specifically discussed about the topic, was conducted. RESULTS: Based on the
      evidence, majority of the management strategies comprise of rapid correction of
      hypoxemia and hypotension, the two most important predictors for mortality.
      However, there is still a need to define the goals for the management of
      hypotension and inclusion of newer difficult airway carts as well as proper
      monitoring devices for ensuring better intubation and ventilatory management.
      Isotonic saline should be used as the first choice for fluid resuscitation. The
      pre-hospital hypothermia has more adverse effects; therefore, this should be
      avoided. CONCLUSION: Most of the management trials published after 2007 have
      focused mainly on the treatment as well as the prevention strategies for
      secondary brain injury. The results of these trials would be certainly adopted by
      new standardized guidelines and therefore may have a substantial impact on the
      pre-hospital management in patients with TBI.

PMID- 24665252
TI  - Delayed Horner's syndrome following ultrasound- guided interscalene brachial
      plexus block.
AB  - We describe a case of Horner's syndrome that occurred shortly after post
      operative bolus administration of interscalene brachial plexus analgesia. 

PMID- 24665253
TI  - Anesthesia for tracheostomy for huge maxillofacial tumor.
AB  - Providing sedation for patients with compromised upper airway is challenging. A
      19-year-old female patient with huge maxillofacial tumor invading the whole
      pharynx scheduled for elective tracheostomy under local anesthesia due to
      compromised airway. The patient had gastrostomy tube for feeding. Venous
      cannulation was totally refused by the patient after repeated trials for
      exhausted sclerosed veins. Pre-operative mixture of dexmedetomidine with ketamine
      was administered through the gastrostomy tube with eutectic mixture of local
      anesthetics cream application over the planned tracheostomy site. The patient was
      sedated with eye opening to command. Local infiltration followed by tracheostomy
      was performed without patient complaints or recall of operative events. 

PMID- 24665254
TI  - Airway management in a patient with Le Fort III Fracture.
AB  - Maxillofacial fractures present unique airway problem to the anesthesiologist.
      Patients with LeFort III fractures are at great risk of requiring emergent airway
      control due to midface instability and oropharyngeal airway obstruction. We
      present a case where difficult intubation was managed with close cooperation
      between the anesthesiologist and the surgeon. 

PMID- 24665255
TI  - Spontaneous migration of central venous catheter tip following extubation.
AB  - Migration of the tip of central venous catheters is not an uncommon event and the
      mechanism for this is not clear. Increased intrathoracic pressure due to
      coughing, sneezing or weight lifting, changing the body position or physical
      movements such as abduction or adduction of the arms is thought to be the cause
      of such migration. We present here a case of a patient with a port catheter tip
      that migrated from the left subclavian to the superior vene cava following
      extubation. 

PMID- 24665257
TI  - Anesthetic management of a 2-day-old with complete congenital heart block.
AB  - Maternal connective tissue disorders such as Systemic Lupus Erythematosus (most
      common), Sjogren's syndrome, mixed connective tissue disorders may lead to the
      rare condition of complete congenital heart block in the neonate. Rare fetal
      syndromes such as myocarditis, 18p syndrome, mucopolysaccharidoses and
      mitochondrial diseases are other causes. The mortality rate of this condition is
      inversely propotional to the age of presentation being 6 % in the neonatal age
      group. As the cardiac output in the neonate is heart rate dependent, it is
      crucial to maintain the heart rate in these patients. Pharamacological
      interventions with dopamine, isoprenaline, epinephrine and atropine are known for
      their variable response. Although permanent pacing is the most reliable mode of
      management, the access to it is often not readily available, especially in the
      developing countries. In such cases temporary pacing methods become lifesaving.
      Of all the modalities of temporary pacing (transcutaneous, transesophageal and
      transvenous) transcutaneous pacing is the most readily available and immediate
      mode. In this case report we present a two day old neonate with isolated complete
      congenital heart block and a resting heart rate of 50-55/min in immediate need of
      palliative surgery for trachea-esophageal fistula (TEF). With pharmacological
      intervention the heart rate could only be raised to 75-80/min. The surgery was
      successfully carried out using transcutaneous pacing to maintain a heart rate of
      100/min. 

PMID- 24665258
TI  - Ventricular arrhythmia during Valsalva maneuver applied to facilitate resection
      of fourth ventricular neurocysticercosis cyst.

PMID- 24665259
TI  - Anesthetic management for elective cesarean section in a case of acromegaly with
      diabetes mellitus.

PMID- 24665260
TI  - A simple technique to avoid difficulty in guide wire insertion during pediatric
      central venous cannulation.

PMID- 24665261
TI  - Anatomical variations of interscalene brachial plexus block: Do they really
      matter?

PMID- 24665262
TI  - Hyperhomocysteinemia: Anesthetic concerns.

PMID- 24665263
TI  - A brachytherapy plan evaluation tool for interstitial applications.
AB  - Radiobiological metrics such as tumor control probability (TCP) and normal tissue
      complication probability (NTCP) help in assessing the quality of brachytherapy
      plans. Application of such metrics in clinics as well as research is still
      inadequate. This study presents the implementation of two indigenously designed
      plan evaluation modules: Brachy_TCP and Brachy_NTCP. Evaluation tools were
      constructed to compute TCP and NTCP from dose volume histograms (DVHs) of any
      interstitial brachytherapy treatment plan. The computation module was employed to
      estimate probabilities of tumor control and normal tissue complications in ten
      cervical cancer patients based on biologically effective equivalent uniform dose
      (BEEUD). The tumor control and normal tissue morbidity were assessed with
      clinical followup and were scored. The acute toxicity was graded using common
      terminology criteria for adverse events (CTCAE) version 4.0. Outcome score was
      found to be correlated with the TCP/NTCP estimates. Thus, the predictive ability
      of the estimates was quantified with the clinical outcomes. Biologically
      effective equivalent uniform dose-based formalism was found to be effective in
      predicting the complexities and disease control. 

PMID- 24665264
TI  - Predictors of venous thromboembolic events associated with central venous port
      insertion in cancer patients.
AB  - Insertion of central venous port (CVP) catheter in the cancer population is
      associated with increased incidence of venous thromboembolic events (VTE).
      However, trials have shown limited benefit of antithrombotic treatment to prevent
      catheter-related venous thrombosis. This prospective observational cohort study
      was designed to assess the incidence of VTE closely related to CVP implantation
      in patients with cancer and undergoing chemotherapy, and to identify a high risk
      subgroup of patients. Between February 2006 and December 2011, 1097 consecutive
      cancer patients with first CVP implantation were included. Catheter-related VTE
      were defined as deep venous thrombosis in the arm, with or without pulmonary
      embolism (PE), or isolated PE. The incidence of CVP-associated VTE was 5.9% (IC95
      4.4-7.3%) at 3 months, and 11.3% (IC95 9.4-13.2%) at 12 months. The incidence of
      any VTE was 7.6% (IC95 6.0-9.3%) at 3 months, and 15.3% (IC95 13.1-17.6%) at 12
      months. High Khorana risk score and lung cancer were significant predictors of 3
      month VTE. In conclusion, this large cohort study of patients with first CVP
      catheter implantation confirms the high incidence of VTE associated with the CVP
      implantation and allow identifying high risk patients who may benefit from
      thromboprophylaxis. 

PMID- 24665265
TI  - Hypertensive encephalopathy.

PMID- 24665266
TI  - Therapeutic effect of insulin in reducing critical illness; polyneuropathy and
      myopathy in the pediatric intensive care unit.
AB  - OBJECTIVE: Hyperglycemia may occur in the patients affected by any kind of
      critical illness. This complication makes an adverse effect on the clinical
      outcome of these patients by causing polyneuropathy and myopathy. It has been
      recently shown that treatment of hyperglycemia with insulin administration
      significantly reduces the prevalence of critical illness polyneuropathy and
      myopathy (CIPNM) and on the other hand reduces the demand for long-term
      mechanical ventilation in the patients admitted to the ICU for more than 1 week.
      The aim of this study was to determine the therapeutic effect of insulin in
      reducing the incidence of CIPNM in the pediatric intensive care unit (PICU).
      MATERIALS & METHODS: In this study, we recruited 30 patients admitted to the PICU
      of Tabriz Pediatric Hospital. The incidence of CIPNM following hyperglycemia was
      evaluated in these patients. The patients were categorized into two groups. In
      the case group, blood sugar was controlled in the range of 140-180mg/dl by
      administration of 0.05 unit per kilogram body weight of insulin as drip protocol
      in an hour and in the control group, placebo was used. Consequently, the
      incidence of CIPNM, duration of PICU and duration of mechanical ventilation were
      compared between the two groups. RESULTS: The incidence of CIPNM and duration of
      PICU stay and mechanical ventilation were significantly reduced in the patients
      treated with insulin compared to the control group. CONCLUSION: This study shows
      that blood sugar control decreases the incidence of CIPNM.

PMID- 24665267
TI  - Comparison of intravenous midazolam drip with intermittent intravenous diazepam
      in the treatment of refractory serial seizures in children.
AB  - OBJECTIVE: Serial seizures occur commonly in inpatient epileptic children. This
      type of seizure due to its characteristics has a significant impact on the
      patient's health. Untreated serial seizures lead to status epilepticus;
      therefore, finding a more effective treatment for such patients is essential.
      This study was performed to compare the outcome of intermittent intravenous
      diazepam in the pediatric neurology clinic and intravenous midazolam in the
      pediatric intensive care unit (PICU), in order to introduce an alternative
      treatment for serail seizures. MATERIALS & METHODS: In this study, 38 inpatient
      children aged 6 mo-15 years with refractory serial seizures were treated by first
      line antiepileptic drugs and then randomly treated with either intermittent
      intravenous diazepam in the neurology ward or intravenous midazolam in PICU.
      RESULTS: Fourteen (70%) diazepam group patients and 13 (72.2%) midazolam group
      patients had good response to treatment, there was no significant difference
      between the two groups. Four midazolam group patients and two diazepam group
      patients needed mechanical ventilation and were intubated during treatment, with
      no significant difference between the two groups. Durations of mechanical
      ventilation and PICU and hospital stay were not significantly different between
      the two groups. CONCLUSION: Intermittent intravenous diazepam is an effective
      alternative therapy for midazolam drip in the treatment of serial seizures due to
      similar therapeutic effects and fewer side effects.

PMID- 24665268
TI  - Relationship between migraine and abnormal EEG findings in children.
AB  - OBJECTIVE: Migraine is a disabling illness that causes absence from school and
      affects the quality of life. It has been stated that headache may represent an
      epileptic event. EEG abnormality is a prominent finding in children with
      migraine. The aim of this study was to evaluate EEG abnormalities in children
      with migraine. MATERIALS & METHODS: Two-hundred twenty-eight children were
      enrolled into the study. Evaluation and following of cases was performed by one
      physician, paraclinical tests were used to increase the accuracy. The study was
      conducted under the supervision of pediatric neurology masters and the selected
      cases were from different parts of the country. RESULTS: Comparing EEG
      abnormalities in different types of migraine revealed that there is an
      association between them. There was also a significant difference between EEG
      abnormalities in different types of aura. Migraine type was associated with the
      patient's age. Sleep disorders were more common in patients with a positive
      family history of seizure. CONCLUSION: Our study dosclosed migraine as a common
      problem in children with abnormalities present in approximately 20% of the
      patients. Migraine and abnormal EEG findings are significantly associated.

PMID- 24665269
TI  - Clinical and Para clinical Manifestations of Tuberous Sclerosis: A Cross
      Sectional Study on 81 Pediatric Patients.
AB  - OBJECTIVE: Tuberous sclerosis complex is an autosomal dominant neurocutaneous
      disease that presents with dermatological, neurological, cardiac, renal and
      ocular symptoms. We described the variable clinical manifestations, neuroimaging
      findings, Age and sex distribution of tuberous sclerosis in a group of 81
      patients referred to our clinic. MATERIALS & METHODS: Based on the diagnostic
      criteria, totally 81 tuberous sclerosis patients with sufficient data were
      enrolled into the study. These children were referred by child neurologists.
      RESULTS: The mean age of the patients was 52 months (range, 7-180 months). There
      were 28 girls and 53 boys. A positive familial history of TSC was seen in 29.6%
      of the patients. Hypo pigmented macules were the most common manifestation
      (82.7%). Facial angiofibroma, shagreen patches, cafe-au-lait lesions and seizure
      were observed in 32.1%, 12.3%, 7.4%. and 74.1% of the studied cases,
      respectively. Infantile spasm was present in the clinical course of 32.1 % of the
      patients. Cortical tubers were the most common MRI finding which were seen in 21
      cases (25.9%). Subepandymal giant cell astrocytoma was seen in four (4.9%)
      patients and intracranial calcification (detected by CT scan) was observed in 18
      (22.2%) of the patients. CONCLUSION: Dermatological and neurological findings
      were the most common symptoms in tuberous sclerosis with a significant
      correlation between them. Thus, careful skin examination is necessary in
      epileptic patients for detection of the mentioned lesions.

PMID- 24665270
TI  - Results of noncontrast brain computed tomography scans of 1-18 year old epileptic
      children.
AB  - OBJECTIVE: The advent of computed tomography (CT) scan revolutionized the
      diagnostic evaluation of neurologic patients. The aim of this study was to
      evaluate brain CT results of epileptic children. MATERIALS & METHODS: In a
      descriptive cross-sectional study, noncontrast brain CT scan of 150 consecutive 1
      18 year old epileptic children whom were referred to pediatric neurology clinic
      of Shahid Sadoughi University of Medical Sciences, from May 2008 to October 2010
      in Yazd-Iran, evaluated. RESULTS: Sixty two girls and 88 boys with mean age of
      6.6 +/- 4.3 years were evaluated. In 38 (25.3 %) children, seizure onset age was
      under one year and 38 others had abnormal mental / developmental status. Fifty
      three children (35.3 %) and 97 (64.7%) had partial and generalized seizures,
      respectively. Partial seizures were more prevalent in children with seizure onset
      in < 1 year [41.5% (22/53) vs. 16.5% (16/97)] Result of CT was normal in 74 %
      (n=111). Among the patients with abnormal results, 18(46%) had brain atrophy, 10
      (25.6%) structural CNS dysgenesia, six (15.4%) intracranial calcification, three
      (7.8%) hydrocephaly and two had (5.2%) brain tumor. Abnormal brain CT was more
      prevalent in patients with seizure onset in less than one year of age [60.5% (23
      of 38) vs. 14.3% (16 of 112), p = 0.003], partial epilepsy [51% (27 of 53) vs.
      12% (12/97)], and abnormal developmental status [ 81.5% (31 of 38) vs.7% (8 of
      112]. Mean age of seizure onset in epileptic children with abnormal brain CT scan
      was less (M +/- SD:1/17 +/- 0.6 years versus 4.02+/-1.9 years). CONCLUSION: Brain
      CT scan might be considered in evaluation of epileptic children with partial
      seizures, seizure onset in less than one year of age or neurodevelopmental delay.

PMID- 24665271
TI  - Epilepsy as a rare neurologic manifestation of oculodentodigitalis dysplasia.
AB  - Oculodentodigitalis dysplasia (ODDD) is an extremely rare inherited disorder
      involving the development of the face, eyes, teeth and limbs. In addition, some
      patients develop neurological problems mostly a spastic paraparesis associated
      with white matter abnormalities on magnetic resonance imaging. This report
      describes a patient with epilepsy, a rare neurologic manifestation of this
      syndrome. 

PMID- 24665272
TI  - A Case Report of Congenital Insensitivity to Pain and Anhidrosis (CIPA).
AB  - Congenital insensitivity to pain and anhidrosis (CIPA) or hereditary sensory
      autonomic neuropathies type IV (HSAN type IV) is an extremely rare autosomal
      recessive disorder initially described by Swanson in 1963. We report a 2.5-year
      old boy with clinical features of CIPA as the first case in Iran. The symptoms
      included recurrent episodes of hyperthermia and unexplained fever that began in
      early infancy, anhidrosis (inability to sweat), profound loss of pain
      sensitivity, neurodevelopmental delay, unconscious self-mutilation of fingers,
      lips and tongue, corneal lacerations, palmar hyperkeratosis, non-painful fracture
      and joint deformities in the right ankle. Tearing, deep tendon reflexes and motor
      and sensory nerve action potentials were normal. Prenatal screening is the sole
      accessible option to prevent the birth of an affected child as no cure is
      available. Early recognition of CIPA patients and its orthopedic complications,
      prevention of accidental injuries, regular visual and eye follow-up and specific
      dental management could be useful in the reduction of frequency and severity of
      complications. 

PMID- 24665273
TI  - Neurologic manifestations of childhood rheumatic diseases.
AB  - Children with rheumatic disorders may have a wide variety of clinical features
      ranging from fever or a simple arthritis to complex multisystem autoimmune
      diseases. Information about the prevalence of neurological manifestations in
      children with rheumatologic disorders is limited. This review describes the
      neurologic complications of childhood Rheumatic disease either solely or combined
      with symptoms of other organs involvement, as a primary manifestation or as a
      part of other symptoms, additionally. 

PMID- 24665274
TI  - Effects of piracetam on pediatric breath holding spells: a randomized double
      blind controlled trial.
AB  - OBJECTIVE: Breath holding spells (BHS) are common paroxysmal non-epileptic events
      in the pediatric population which are very stressfull despite their harmless
      nature. There has been no specific treatment found for the spells yet. The aim of
      this study was to evaluate the efficacy of piracetam (2-oxo-l-pyrrolidine) on
      these children. MATERIALS & METHODS: In this randomized double blind clinical
      trial study, 150 children with severe BHS referred to our pediatric outpatient
      service were enrolled from August 2011 to July 2012. The patients were randomized
      into two equal groups. One received 40mg/kg/day piracetam and the other group
      received placebo, twice daily. Patients were followed monthly for three months.
      The number of attacks/month before and after treatment were documented. RESULTS:
      Of the enrolled patients, 86 were boys. The mean age of the patients was 17
      months (range, 6 to 24 months). In the piracetam group, 1 month after treatment
      an 81% response to treatment was found. In the placebo group, none of the
      patients had complete remission and 7% of the cases had partial remission.
      Overall, control of breath-holding spells was observed in 91% of the patients in
      the group taking piracetam as compared with 16% in the group taking placebo at
      the end of the study. There was no significant difference detected between the
      groups regarding the prevalence of drug side effects. CONCLUSION: A significant
      difference was detected between piracetam and placebo in prevention and
      controlling BHS. Piracetam (40mg/kg/day) had a good effect on our patients.

PMID- 24665275
TI  - Atypical findings of guillain-barre syndrome in children.
AB  - OBJECTIVE: Guillain-Barre syndrome (GBS) is an immune-mediated polyneuropathy
      that occurs mostly after prior infection. The diagnosis of this syndrome is
      dependent heavily on the history and examination, although cerebrospinal fluid
      analysis and electrodiagnostic testing usually confirm the diagnosis. This is a
      retrospective study which was performed to investigate the atypical features of
      GBS. MATERIALS & METHODS: Thirty three patients (21/63.6% males and 12/36.4%
      females) with GBS were retrospectively studied and prospectively evaluated at the
      Child Neurology institute of Mofid Children Hospital of Shahid Beheshti
      University of Medical Sciences between May 2011 and September 2012. RESULTS: The
      mean age was 5.4 years (range, 1.5-10.5).Twenty one patients (87.9%) had previous
      history of infections. Eight patients (24.2%) admitted with atypical symptoms
      like upper limb weakness (3%), ptosis (3%), neck stiffness (3%), inability to
      stand (proximal weakness) (9.1%), headache (3%) and dysphagia (3%).According to
      disease process, weakness was ascending in 26 (78.8%), descending in 5 (15.2%)
      and static in 2 (6.1%) patients. Cranial nerve involvement was found in 8(24.3%)
      children, most commonly as facial palsy in 3 (9.1%). CONCLUSION: In this study,
      24.3% of our patients presented with atypical symptoms of GBS as upper limb
      weakness, ptosis, neck stiffness, inability to stand (proximal weakness),
      headache and dysphagia.

PMID- 24665276
TI  - Efficacy of levothyroxine in migraine headaches in children with subclinical
      hypothyroidism.
AB  - OBJECTIVE: Hypothyroidism may be an exacerbating factor for primary headaches and
      migraine is one of the most common primary headaches in childhood. The purpose of
      this study was to evaluate the effect of treatment of subclinical hypothyroidism
      on children with migraine headache. MATERIALS & METHODS: In a quasi-experimental
      study, the severity and monthly frequency of headache of 25 migraineur children
      with subclinical hypothyroidism who were referred to the pediatric neurology
      clinic of Shahid Sadoughi University of Medical Sciences,Yazd, Iran between
      January 2010 and February 2011 and were treated with levothyroxine for two months
      were evaluated. RESULTS: Thirteen girls (52%) and 12 boys (48%) with the mean age
      of 10.2 +/- 2.76 years were evaluated. In children with hypothyroidism, the
      monthly frequency of headache (mean +/- SD: 17.64 +/- 9.49 times vs. 1.2 +/- 1.1
      times) and the severity of headache (mean+/- SD: 6.24+/-1.8 scores vs. 1.33 +/-
      0.87 scores) were significantly decreased by treatment. CONCLUSION: Based on the
      results of this study, treatment of subclinical hypothyroidism was effective in
      reducing migraine headaches. Therefore, it is logical to check thyroid function
      tests in migraineur children.

PMID- 24665277
TI  - Iron status and febrile seizure- a case control study in children less than 3
      years.
AB  - OBJECTIVE: Febrile seizure is one of the most common neurological conditions of
      childhood. Several theories, such as iron deficiency anemia have been proposed as
      the pathogenesis of this condition. The aim of this study was to find the
      association between iron deficiency anemia and febrile seizures in children aged
      6 months to 3 years admitted in Valie Asr hospital in Zanjan. MATERIALS &METHODS:
      Hemoglobin (Hb), mean corpuscular volume (MCV), serum iron (SI), total iron
      binding capacity (TIBC) and SI/TIBC ratio were assessed in one hundred children
      with febrile seizures and compared to the values of one hundred healthy children
      presenting in a heath care center in the same period as the control group.
      RESULTS: A total of 6% of cases had iron deficiency anemia which was similar to
      the control group. In the case group SI/TIBC ratio below 12% was seen in 58% of
      children which was significantly higher than that of the control group (29%).
      CONCLUSION: The results of this study suggest that although anemia was not common
      among febrile seizure patients, iron deficiency was more frequent in these
      patients.

PMID- 24665278
TI  - Febrile seizure: demographic features and causative factors.
AB  - OBJECTIVE: Because of geographical and periodical variation, we prompted to
      determine the demographic features and causative factors for febrile seizure in
      Rasht. MATERIALS & METHODS: In this cross-sectional study, all 6-month- to 6-year
      old children with the diagnosis of febrile seizure admitted to 17 Shahrivar
      hospital in Rasht, from August, 2009 to August, 2010 were studied. Age, sex,
      family history of the disease, seizure types, body temperature upon admission and
      infectious causes of the fever were recorded. All statistical analysis was
      performed with SPSS software, version 16. RESULTS: Of the 214 children (mean age,
      25.24+/-15.40 months), 124 were boys and 109 had a positive family history.
      Complex seizures were seen in 39 cases. In patients with a complex febrile
      seizure, 59% had the repetitive type, 20.5% had the focal type and 20.5% had more
      than 15 minutes duration of seizures. Most of the repetitive seizures (78.3%)
      occurred in patients under 2 years old; the difference between under and over 2
      year-old patients was statistically significant. Study results did not show
      significant differences between the two genders for simple or complex seizures.
      The mean body temperature upon admission was 38.2+/-1.32?C (38.31+/-0.82 degrees
      in boys and 38.04+/-1.78 in girls). Upper respiratory infections were seen in
      most patients (74.29%). All cases of lower respiratory infections were boys.
      There was a statistically significant difference between boys and girls in causes
      of fever. CONCLUSION: Most of the children had a positive family history and the
      most common causative factor was upper respiratory infection.

PMID- 24665279
TI  - Effects of stress on mothers of hospitalized children in a hospital in iran.
AB  - OBJECTIVE: Hospitalization of a child can cause severe anxiety and stress in the
      parents, especially for the mother. This stress consequently affects the
      treatment course of the child. Hereby, we investigate the impact of different
      stressors in mothers of hospitalized children. MATERIALS & METHODS: In this cross
      sectional study, 225 mothers of hospitalized children in the pediatric ward of
      Besat hospital were randomly selected and studied. Data collection tool was a two
      part questionnaire gathered by interviewing the mother. The first part included
      demographic information of the patients. The second part included questions
      regarding stressors in four different categories; child-related factors,
      environmental factors, socioeconomic factors and health professional factors.
      SPSS 16.5 was used for statistical analysis and data were analyzed by one way
      ANOVA and T test. RESULTS: In the child-related factor category, fear of child
      death (84%); in the socioeconomic factor category, fear of disease in the other
      siblings (84%); in the environmental factor category, unpleasant odors in the
      ward (56%); and in the health professional category, not enough explanation about
      inserting IV lines, (54.2%) constituted the most important factors. There was a
      meaningful correlation between the stressors and the mothers' age and occupation,
      child age, days of hospitalization, types of admission and health insurance
      coverage, but there was no meaningful correlation between stressors and other
      factors. CONCLUSION: Professional and in depth training programs should be
      provided for health care providers and nursing staff regarding dealing with
      mothers of hospitalized children.

PMID- 24665280
TI  - A case of schizencephaly and septo-optic dysplasia presenting with anterior
      encephalocele.
AB  - Schizencephaly is a rare central nervous system disorder with variable
      presentations. Here we report a patient with a huge bilateral schizencephaly and
      septo-optic dysplasia presenting with anterior encephalocele. 

PMID- 24665281
TI  - Digital and dental malformation and short stature in a patient with neurological
      problems: a variant of the oculodentodigital dysplasia syndrome or a new
      syndrome?
AB  - Several syndromes have been recognized with digital abnormality and CNS
      involvement such as oculodentodigital dysplasia (ODDD), Mohr syndrome and Joubert
      syndrome. We report a patient who was referred to us because of the neurological
      signs suspicious of metabolic disorders. This case was a 22-year-old woman whose
      problems began 4 years ago with shortening of memory, ataxia, abnormal gait and
      diplopia which progressed slowly. She consulted many neurologists and was on
      treatment with the suspicion of vasculitis, but no response was detected. She had
      severe short stature, hypoplasia of the middle and distal phalanges of the first,
      second and third fingers, clinodactyly, abnormal toes, abnormal enamel and
      missing teeth. She had no characteristic faces of ODDD and ophthalmological
      abnormality. Our patient might be a variant of ODDD or a new syndrome with
      somatic and neurologic signs. 

PMID- 24665282
TI  - NCL Disorders: Frequent Causes of Childhood Dementia.
AB  - Dementia in children or young adults is most frequently caused by neuronal
      ceroidlipofuscinoses (NCL), a group of incurable lysosomal storage disorders
      linked by the accumulation of a characteristic intracellular storage material and
      progressive clinical deterioration, usually in combination with visual loss,
      epilepsy, and motor decline. The clinical characteristics can vary and the age at
      disease onset ranges from birth to over 30 years. Diagnosis of an NCL is
      difficult because of genetic heterogeneity with14 NCL forms (CLN1-CLN14)
      identified and a high phenotype variability. A new classification of the
      disorders is based on the affected gene and the age at disease onset and allows a
      precise and practicable delineation of every NCL disease. We present a clear
      diagnostic algorithm to identify each NCL form. A precise diagnosis is essential
      for genetic counseling of affected families and for optimizing palliative care.
      As patient management profits from recognizing characteristic complications, care
      supported by a specialized team of NCL clinicians is recommended. The development
      of curative therapies remains difficult as the underlying pathophysiological
      mechanism remains unclear for all NCL forms. 

PMID- 24665283
TI  - Prophylaxis of childhood migraine: topiramate versus propranolol.
AB  - OBJECTIVE: Headache is a common disabling neurological disorder and migraine
      comprises more than half the causes of recurrent headaches in children. Despite
      extended prevalence of this type of headache there is lack of evidence about best
      drug treatment for migraine. So we aimed to compare the therapeutic effects of
      these drugs on childhood migraine. MATERIALS & METHODS: In the current study, a
      randomized clinical trial consisting of 78 patients according to 2004
      International Headache Association criteria were randomly assigned to two groups
      that matched by age and sex. One of these two groups was treated with Topiramate,
      while the other was given Propranolol. After one and four months, the efficiency
      of these treatments was measured in terms of frequency, severity and duration of
      migraine attacks. RESULTS: Results obtained from the data collected showed that
      of these 78 studied patients, 38 patients received Topiramate treatment (group A)
      and the rest (40 patients; group B) was treated with Propranolol. The average age
      of group A was 8.5+/- 2.9 years and that of group B was 8.3 +/- 2.8 years. No
      significant difference was observed between these two groups in terms of
      reduction in frequency, severity and duration of migraine attacks. CONCLUSION:
      Results showed that both treatments had the same efficiency in healing migraine
      headaches and there was no significant difference between their treating results.
      However, further studies are needed to examine medical effects of these two
      medicines.

PMID- 24665284
TI  - Sleep Inducing for EEG Recording in Children: A Comparison between Oral Midazolam
      and Chloral Hydrate.
AB  - OBJECTIVE: Electroencephalography (EEG) recording is a long duration procedure
      that needs patient's cooperation for device setup and performing the procedure.
      Many children lose their cooperation during this procedure. Therefore, sedation
      and sleep are frequently induced using a few agents as pre procedure medication
      in children before EEG recording. We aimed to compare the sedative effects of
      oral midazolam versus chloral hydrate before the procedure along with their
      impacts on EEG recording in children. MATERIALS & METHODS: A randomized trial was
      carried out to compare the sedative effects of oral midazolam versus chloral
      hydrate and their impacts on EEG recording in children. A total of 198 children
      (100 in the midazolam group and 98 in the chloral hydrate group) were enrolled in
      the study and randomly allocated to receive either oral moidazolam or chloral
      hydrate. RESULTS: Oral midazolam had superiority neither in sleep onset latency
      nor in sleep duration when compared to chloral hydrate. Moreover, the yield of
      epileptiform discharges in the chloral hydrate group was more than the midazolam
      group. CONCLUSION: The results of this study showed that both chloral hydrate 5%
      (one ml/kg) and oral midazolam (0.5 mg/kg) could be administered as a pre
      medication agent for EEG recording in children. However, oral midazolam at this
      dose had no advantage compared with chloral hydrate.

PMID- 24665285
TI  - The role of chest physiotherapy in prevention of postextubation atelectasis in
      pediatric patients with neuromuscular diseases.
AB  - OBJECTIVE: There are controversial findings in the literature on the effects of
      chest physiotherapy on postextubation lung collapse in pediatric age group.
      Therefore, we aimed to investigate the efficacy of chest physiotherapy in
      prevention of postextubation atelectasis in pediatric patients. MATERIALS &
      METHODS: In a case-control study from March 2007 to March 2011, two groups of
      patients (35 patients in each group) susceptible to lung collapse were enrolled
      in the study. The studied patients had neuromuscular diseases such as spinal
      muscular atrophy, Guillain-Barre syndrome, critical illness
      polyneuropathy/myopathy, and cerebral palsy. The patients were randomly divided
      into two groups (case and control); The case group underwent daily chest
      physiotherapy through vibrator and chest percussion and the control group was
      under supervision. In the latter group, the underlying disease was treated and
      the lung collapse was managed, if occurred. RESULTS: The frequency of atelectasis
      was lower in the case group who received prophylactic chest physiotherapy
      compared to the control group (16.6% vs. 40%). CONCLUSION: Chest physiotherapy as
      well as appropriate and regular change of position can considerably reduce the
      rate of pulmonary collapse in pediatric patients.

PMID- 24665286
TI  - CNS structural anomalies in Iranian children with global developmental delay.
AB  - OBJECTIVE: Central Nervous system (CNS) malformations are one of the most
      important causes of global developmental delay (GDD) in Children. About one
      percent of infants with GDD have an inherited metabolic disorder and 3-10 percent
      have a chromosomal disorder. This study aimed to survey the frequency of brain
      structural anomalies and their subtypes among the variety of etiologic factors in
      children with GDD in our patients. MATERIALS & METHODS: This study used the
      results of neuroimaging studies [unenhanced brain Magnetic Resonance Imaging
      (MRI)] of all children who had been referred for evaluation of GDD to outpatient
      Clinic of Pediatric neurology at Children's Medical Center affiliated to Tehran
      University of Medical Science between September 2009 and September 2010. RESULTS:
      In this study, unenhanced brain MRI was performed on 405 children, of which 80
      cases (20 percent) had brain structural anomalies. In 8.7 percent of the cases,
      previous history of brain structural disorders existed in other children of the
      family and 20 percent of mothers had inadequate consumption of folate during
      pregnancy. CONCLUSION: Based on the results of this study, unenhanced cranial MRI
      seems to be a fundamental part of evaluation in all children with GDD. Adequate
      folate consumption as prophylaxis as well as genetic counseling can be worthy for
      high-risk mothers who have previous history of CNS anomaly or miscarriage to
      avoid repeated CNS anomalies in their next pregnancies.

PMID- 24665287
TI  - Evaluation of the young children with neurodevelopmental disability: a
      prospective study at hamadan university of medical sciences clinics.
AB  - OBJECTIVE: Developmental impairment is a common problem in children health that
      occurs in approximately 5-10% of the childhood population. The aim of this study
      was to determine the etiologic yield of subspecialists' evaluation of young
      children with developmental disability. MATERIALS & METHODS: All children aged
      between 2 months and 5 years referred over a 15-month period to Hamadan
      University of Medical Sciences subspecialty services for initial evaluation of a
      suspected developmental Disability, were enrolled in the present study.
      Diagnostic yield was determined after the completion of clinical assessments and
      laboratory tests requested by the evaluating physician. RESULTS: A total of 198
      children (129 boys and 69 girls) were eligible for our study. 108 children had
      global developmental delay and 90 children had isolated developmental delay.
      Approximately 1/4 of all patients did not have any specific etiology for
      developmental disability. Cerebral palsy (CP) was the most common clinical
      syndrome in all patients (41.4%). Hypoxic ischemic encephalopathy (13.8%), brain
      dysgenesis (13%), genetic disorder (13%), and neurodegenerative diseases (11%)
      were determined in more than one half of all children with global developmental
      disability. in our study, "developmental speech delay" was the common cause of
      isolated speech delay. CONCLUSION: Determination of an underlying etiology is an
      essential part of specialty evaluation of young children with developmental
      disability. The results of this study were similar closely to the results of
      other studies.

PMID- 24665288
TI  - Association of Brucella meningoencephalitis with cerebrospinal fluid shunt in a
      child: a case report.
AB  - OBJECTIVE: Brucellosis is an endemic zoonosis in Iran. It is a systemic infection
      that can involve any organs or systems of the body and have variable
      presentations. Ventriculoperitoneal (VP) shunt infections due to brucellosis have
      been rarely reported in the literatures. This is the history of a four years old
      boy who developed Brucella meningoencephalitis at the age of 42 months, whilst he
      had a VP shunt in situ for hydrocephalus treatment. Also, he presented
      brucellosis as acute abdomen. This patient was treated with trimethoprim
      sulfamethoxazole, gentamicin and rifampicin. The shunt was extracted and all
      clinical and laboratory test abnormalities subsided through this management. We
      propose that in a patient with Brucella meningoencephalitis, the cerebrospinal
      fluid shunt system can be extracted and treatment with appropriate combination of
      antibiotics could be successful. Moreover, it shows that brucellosis should be
      considered in the differential diagnosis for acute abdomen and ascites in endemic
      regions.

PMID- 24665289
TI  - Joubert syndrome in three children in a family: a case series.
AB  - Joubert syndrome (JS) is a rare autosomal recessive central nervous system
      malformation characterized by hypoplasia of the cerebellar vermis, hypotonia and
      abnormal psychomotor development, along with altered respiratory pattern and
      various ophthalmologic features. Here, we describe three children with Joubert
      syndrome in a family that had almost similar presentations, including ataxia,
      developmental delay, mental retardation and ocular disorders. Prevalence of
      Joubert syndrome is about 1 in 100,000 live birth. It may be accompanied by other
      organs' disorders. The molar tooth sign is pathognomonic for joubert syndrome
      that is ascertained by brain MRI. 

PMID- 24665290
TI  - Multiple sclerosis in children.
AB  - Multiple sclerosis (MS) is the most important immune-mediated demyelinated
      disease of human which is typically the disease of young adults. A total of 4% to
      5% of MS population are pediatric. Pediatric MS is defined as the appearance of
      MS before the age of sixteen. About 80% of the pediatric cases and nearly all
      adolescent onset patients present with attacks typical to adult MS. Approximately
      97% to 99% of the affected children have relapsing-remitting MS, while 85% to 95%
      of the adults experience such condition. MS in children is associated with more
      frequent and severe relapses. Treatment is the same as adults. We aimed to review
      the epidemiology, etiology, clinical manifestations, and treatment of MS in
      children. 

PMID- 24665291
TI  - A comparative study of the sedative effect of oral midazolam and oral
      promethazine medication in lumbar puncture.
AB  - OBJECTIVE: Lumbar puncture (LP) essentially is a painful and stressful procedure,
      however indicated for diagnosis and therapeutic purposes. One way to reduce the
      anxiety is to administer an oral premedication. The aim of this study is to
      compare clinical effects of oral midazolam and oral promethazine in LP. MATERIALS
      & METHODS: This prospective randomized controlled clinical trial study was
      performed on 80 children aged 2-7 years that were candidate for LP. They were
      divided into two randomized equal groups. First group received oral midazolam
      syrup 0.5 mg/kg and the other group received oral promethazine syrup 1mg/kg.
      Level of sedation, hemodynamic changes and any other complications were monitored
      every 5 minutes from 30 minutes before the start of the procedure. RESULTS:
      Midazolam group and promethazine group were similar in age, gender and weight.
      Midazolam had significantly shorter onset of sedation and also shorter duration
      to maximal sedation. The two groups were similar with respect to sedative effect
      at all time. The only complication that was significantly more in midazolam group
      was nausea and vomiting. CONCLUSION: Midazolam syrup and promethazine syrup have
      same sedative effect in children. Both of these medications are easy to use in
      preschool children and none of them appeared to be superior to another.

PMID- 24665292
TI  - Evaluation of one hundred pediatric muscle biopsies during a 2-year period in
      mofid children and toos hospitals.
AB  - OBJECTIVE: Muscle biopsy is a very important diagnostic test in the investigation
      of a child with suspected neuromuscular disorder. The goal of this study was to
      review and evaluate pediatric muscle biopsies during a 2-year period with focus
      on histopathology diagnosis and correlations with other paraclinic studies.
      MATERIALS & METHODS: We investigated 100 muscle biopsies belonging to patients
      with clinical impression of neuromuscular disorder. These patients have been
      visited consecutively by pediatric neurologists during 2010 to 2012. Samples were
      investigated by standard enzyme histochemical and immunohistochemical techniques.
      RESULT: Sixty-nine (69%) males and 39 (39%) females with a mean age of 5.7 years
      were evaluated. Major pathologic diagnoses were Muscular dystrophy (48 cases),
      Neurogenic atrophy (18 cases), nonspecific myopathic atrophy (12cases),
      congenital myopathy (6 cases), storage myopathies (4 cases) and in 6 cases there
      was no specific histochemical pathologic finding. EMG was abnormal in 79 cases.
      Degree of correlation between EMG and biopsy result was significant in children
      >= 2 years of age. CONCLUSION: This study confirms the high diagnostic yields of
      muscle biopsy especially only if standard and new techniques such as enzyme study
      and immunohistochemistry are implemented. Also, we report 11 cases of Merosin
      negative congenital muscular dystrophy. This is the largest documented case
      series of Merosin deficient congenital muscular dystrophy reported from Iran.

PMID- 24665293
TI  - A Novel Deletion Mutation in ASPM Gene in an Iranian Family with Autosomal
      Recessive Primary Microcephaly.
AB  - OBJECTIVE: Autosomal recessive primary microcephaly (MCPH) is a
      neurodevelopmental and genetically heterogeneous disorder with decreased head
      circumference due to the abnormality in fetal brain growth. To date, nine loci
      and nine genes responsible for the situation have been identified. Mutations in
      the ASPM gene (MCPH5) is the most common cause of MCPH. The ASPM gene with 28
      exons is essential for normal mitotic spindle function in embryonic neuroblasts.
      MATERIALS & METHODS: We have ascertained twenty-two consanguineous families with
      intellectual disability and different ethnic backgrounds from Iran. Ten out of
      twenty-two families showed primary microcephaly in clinical examination. We
      investigated MCPH5 locus using homozygosity mapping by microsatellite marker.
      RESULT: Sequence analysis of exon 8 revealed a deletion of nucleotide (T) in
      donor site of splicing site of ASPM in one family. The remaining nine families
      were not linked to any of the known loci .More investigation will be needed to
      detect the causative defect in these families. CONCLUSION: [corrected] We
      detected a novel mutation in the donor splicing site of exon 8 of the ASPM gene.
      This deletion mutation can alter the ASPM transcript leading to functional
      impairment of the gene product.

PMID- 24665294
TI  - Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross
      Sectional Study.
AB  - OBJECTIVE: Dravet syndrome or severe myoclonic epilepsy of infancy (SMEI) is a
      baleful epileptic encephalopathy that begins in the first year of life. This
      syndrome specified by febrile seizures followed by intractable epilepsy,
      disturbed psychomotor development, and ataxia. Clinical similarities between
      Dravet syndrome and generalized epilepsy with febrile seizure plus (GEFS+)
      includes occurrence of febrile seizures and joint molecular genetic etiology.
      Shared features of these two diseases support the idea that these two disorders
      represent a severity spectrum of the same illness. Nowadays, more than 60
      heterozygous pattern SCN1A mutations, which many are de novo mutations, have been
      detected in Dravet syndrome. MATERIALS & METHODS: From May 2008 to August 2012,
      35 patients who referred to Pediatric Neurology Clinic of Mofid Children Hospital
      in Tehran were enrolled in this study. Entrance criterion of this study was
      having equal or more than four criteria for Dravet syndrome. We compared clinical
      features and genetic findings of the patients diagnosed as Dravet syndrome or
      GEFS+. RESULTS: 35 patients (15 girls and 20 boys) underwent genetic testing.
      Mean age of them was 7.7 years (a range of 13 months to 15 years). Three criteria
      that were best evident in SCN1A mutation positive patients are as follows:
      "Normal development before the onset of seizures, onset of seizure before age of
      one year, and psychomotor retardation after onset of seizures. Our genetic
      testing showed that 1 of 3 (33.3%) patients with clinical Dravet syndrome and 3
      of 20 (15%) patients that diagnosed as GEFS+, had SCN1A mutation. CONCLUSION: In
      this study, normal development before seizure onset, seizures beginning before
      age of one year and psychomotor retardation after age of two years are the most
      significant criteria in SCN1A mutation positive patients.

PMID- 24665295
TI  - Zonisamide efficacy as adjunctive therapy in children with refractory epilepsy.
AB  - OBJECTIVE: Approximately one third of epileptic children do not achieve complete
      seizure improvement. Zonisamide is a new antiepileptic drug which is effective as
      adjunctive therapy in treatment of intractable partial seizures. The purpose of
      the current study was to evaluate the effectiveness, safety, and tolerability of
      Zonisamide in epileptic children. MATERIALS & METHODS: From November 2011 until
      October 2012, 68 children who referred to Children's Medical Center and Mofid
      Children Hospital due to refractory epilepsy (failure of seizure control with the
      use of two or more anticonvulsant drugs) entered the study. The patients were
      treated with Zonisamide by dose of 2- 12 mg/kg daily in addition to the previous
      medication. We followed the children every three to four-weeks intervals based on
      daily frequency, severity and duration of seizures. During the follow-up equal
      and more than fifty percent reduction in seizure frequency or severity known as
      response to the drug. RESULTS: In this study 68 patients were examined that 61
      children reached the last stage.35 (57.4%) were male and 26 (42.6%) patients were
      female. After first and six months of Zonisamide administration daily seizure
      frequency decreased to 2.95+/-3.54 and 3.73+/-3.5 respectively. There was
      significant difference between seizure frequency in first and six month after
      Zonisamide toward initial attacks. After six months ZNS therapy a little side
      effects were created in 10 patients (16.4%) including stuttering(4.9%), decreased
      appetite (4.9%), hallucination (1.6%), dizziness(1.6%), blurred vision(1.6%) and
      suspiring(1.6%) as all of them eliminated later dosage reduction. CONCLUSION:
      This study confirms the short term efficacy and safety of Zonisamide in children
      with refractory epilepsies.

PMID- 24665296
TI  - Joubert syndrome with variable features: presentation of two cases.
AB  - Joubert syndrome is a very rare disorder characterized by respiratory
      irregularities, nystagmus, hypotonia, and global developmental delay with
      abnormalities of cerebellum. We present two cases of this syndrome with different
      phenotypes. The first case was an 8-month-old girl with hypotonia, apnea, and
      mild developmental delay as well as retinal degeneration and unilateral renal
      cystic dysplasia. The second case was a 27-month-old boy who presented with
      episodes of hyperpnea, apnea, retinal dystrophy, and severe global developmental
      delay. Both patients had normal metabolic profile and prototype imaging of
      joubert syndrome including vermis agenesis and molar tooth sign. 

PMID- 24665297
TI  - Spontaneous ventral spinal epidural hematoma in an infant: an unusual
      presentation.
AB  - Spontaneous ventral spinal epidural hematomas are extremely rare in children and
      clinically recognized by the appearance of acute asymmetric focal motor and
      sensory involvement. In infants, the initial presenting symptoms are very non
      specific and irritability is often the only initial manifestation. Appearance of
      other neurological signs may be delayed up to hours or even days later. In the
      absence of significant precipitating factors such as severe trauma or previously
      known coagulopathies, the diagnosis is usually delayed until the full picture of
      severe cord compression is developed. The diagnosis is finally made by performing
      magnetic resonance imaging. We report a 5-month-old infant with spinal epidural
      hematoma who presented with symmetrical upper limb weakness and diaphragmatic
      involvement to highlight the importance of recognizing the atypical
      manifestations for early diagnosis and intervention. 

PMID- 24665298
TI  - Acute necrotizing encephalopathy of childhood; a case report.
AB  - Acute necrotizing encephalopathy of childhood (ANEC) is a disease characterized
      by respiratory or gastrointestinal infection and high fever accompanying with
      rapid alteration of consciousness and seizures. This disease is nearly
      exclusively seen in East Asian infants and children who had previously been
      completely healthy. Serial magnetic resonance imaging examinations have
      demonstrated symmetric lesions involving the thalami, brainstem, cerebellum, and
      white matter in this disease. The condition accompanies a poor prognosis with
      high morbidity and mortality rates. A 22-month-old toddler with ANEC hospitalized
      in Amirkola Children Hospital is being reviewed. 

PMID- 24665299
TI  - Approach To The First Unprovoked Seizure- PART I.
AB  - The approach to a child who has experienced a first unprovoked generalized tonic
      clonic seizure is challenging and at the same time controversial. How to
      establish the diagnosis, ways and means of investigation and whether treatment is
      appropriate, are different aspects of this subject. In this writing the above
      mentioned matters are discussed. 

PMID- 24665300
TI  - Paraneoplastic neurologic syndromes in children: a review article.
AB  - OBJECTIVE: Paraneoplastic neurological syndromes (PNS) were initially defined as
      neurological syndromes with unknown etiology that often associate with cancer.
      This broad definition may lead to misconception that any neurological syndrome,
      which coincides with a cancer might be considered as PNS. In the last two decades
      it has been suggested that PNSs are mainly immune-mediated. The detection of
      onconeural antibodies has been very helpful in indicating the existence of a
      tumor and defining a given neurological syndrome as paraneoplastic. However, PNS
      may occur without onconeural antibodies, and the antibodies can occur with no
      neurological syndrome; thus, their presence should not be the only condition to
      define a neurological syndrome as paraneoplastic. Diagnosis of paraneoplastic
      syndromes in children may result in early detection and treatment of the
      pediatric cancer and can reduce the neurological damage that is the major source
      of morbidity in children with successfully treated tumors. This study reviews the
      presenting symptoms, immunology, and management options for paraneoplastic
      syndromes, focusing on those most commonly reported in children.

PMID- 24665301
TI  - Ullrich Congenital Muscular Dystrophy (UCMD): Clinical and Genetic Correlations.
AB  - OBJECTIVE: Ullrich congenital muscular dystrophy (UCMD) corresponds to the severe
      end of the clinical spectrum of neuromuscular disorders caused by mutations in
      the genes encoding collagen VI (COL VI). We studied four unrelated families with
      six affected children that had typical UCMD with dominant and recessive
      inheritance. MATERIALS & METHODS: Four unrelated Iranian families with six
      affected children with typical UCMD were analyzed for COLVI secretion in skin
      fibroblast culture and the secretion of COLVI in skin fibroblast culture using
      quantitative RT-PCR (Q-RT-PCR), and mutation identification was performed by
      sequencing of complementary DNA. RESULTS: COL VI secretion was altered in all
      studied fibroblast cultures. Two affected sibs carried a homozygous nonsense
      mutation in exon 12 of COL6A2, while another patient had a large heterozygous
      deletion in exon 5-8 of COL6A2. The two other affected sibs had homozygote
      mutation in exon 24 of COL6A2, and the last one was homozygote in COL6A1.
      CONCLUSION: In this study, we found out variability in clinical findings and
      genetic inheritance among UCMD patients, so that the patient with complete
      absence of COLVI was severely affected and had a large heterozygous deletion in
      COL6A2. In contrast, the patients with homozygous deletion had mild to moderate
      decrease in the secretion of COL VI and were mildly to moderately affected.

PMID- 24665302
TI  - Antiepileptic drug-related adverse reactions and factors influencing these
      reactions.
AB  - OBJECTIVE: According to the basic role of drug side effects in selection of an
      appropriate drug, patient compliance and the quality of life in epileptic
      patients, and forasmuch as new drugs with unknown side effect have been
      introduced, necessity of this research is explained. This study was conducted to
      evaluate the incidence and clinical characteristics of anti epileptic drug (AED)
      related adverse reactions in children. MATERIAL & METHODS: In this descriptive
      study, children less than 14 years old with AED side effects referred to the
      Children's Medical Center and Mofid Childeren's Hospital (Tehran, Iran) were
      evaluated during 2010-2012. The informations were: sex, age, incriminating drug,
      type of drug side effect, incubation period, history of drug usage, and patient
      and family allergy history. Exclusive criterions were age more than 14 years old
      and reactions due to reasons other than AEDs. RESULTS: A total of 70 patients
      with AED reaction were enrolled in this study. They included 26 (37%) females and
      44 (63%) males. The maximum rate of incidence was seen at age less than 5 years
      old. All the patients had cutaneous eruptions that the most common cutaneous drug
      eruption was maculopapular rash. The most common culprit was phenobarbital (70%)
      and the least common was lamotrigine (1.4%). CONCLUSION: In this study, we found
      higher rates of drug rash in patients treated with aromatic AEDs and lower rates
      with non-aromatic AEDs. Various endogenous and environmental factors may
      influence the propensity to develop these reactions.

PMID- 24665303
TI  - A study on causes and types of abnormal increase in infants' head circumference
      in kashan/iran.
AB  - OBJECTIVE: Head circumference is a valuable index of brain growth and its
      disturbances can indicate different disorders of nervous system. Abnormal
      increased head circumference (macrocephaly) is common and observed in about 2% of
      infants. In this study, the causes and clinical types of abnormal increase in
      infants' head circumference were investigated in Kashan, Iran. MATERIALS AND
      METHODS: This cross-sectional study was performed on 90 infants less than 2 years
      of age with abnormal increase in head circumference in Kashan, during 2009- 2011.
      The data were collected by history taking, physical examination, growth chart,
      and imaging. RESULTS: 65 (72%) cases out of 90 infants were male and 25 ( 28%)
      cases were female. Fifty-three (58.8%) cases had familial megalencephaly, 30
      (33.4%) had hydrocephalus, and other causes were observed in 7 (7.8%) cases.
      Eighty-three percent of Infants with familial megalencephaly and 50% with
      hydrocephalus had normal fontanels. In 90.6% of cases with familial
      megalencephaly, family history for large head was positive. Motor development was
      normal in 100% of cases with familial megalencephaly and 76.7% of hydrocephalic
      infants. CONCLUSION: Familial megalencephaly was the most common cause of
      macrocephaly in the studied infants, and most of them had normal physical
      examination and development, so, parental head circumferences should be
      considered in the interpretation of infant's head circumference and in cases of
      abnormal physical examination or development, other diagnostic modalities,
      including brain imaging should be done.

PMID- 24665304
TI  - CSWS Versus SIADH as the Probable Causes of Hyponatremia in Children With Acute
      CNS Disorders.
AB  - OBJECTIVE: There is a major problem about the incidence, diagnosis, and
      differentiation of cerebral salt wasting syndrome (CSWS) and syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH) in patients with acute
      central nervous system (CNS) disorders. According to rare reports of these cases,
      this study was performed in children with acute CNS disorders for diagnosis of
      CSWS versus SIADH. MATERIALS & METHODS: This prospective study was done on
      children with acute CNS disorders. The definition of CSWS was hyponatremia (serum
      sodium <=130 mEq/L), urine volume output >=3 ml/kg/hr, urine specific gravity
      >=1020 and urinary sodium concentration >=100 mEq/L. Also, patients with
      hyponatremia (serum sodium <=130 mEq/L), urine output < 3 ml/kg/hr, urine
      specific gravity >=1020, and urinary sodium concentration >20 mEq/L were
      considered to have SIADH. RESULTS: Out of 102 patients with acute CNS disorders,
      62 (60.8%) children were male with mean age of 60.47+/-42.39 months. Among nine
      children with hyponatremia (serum sodium >=130 mEq/L), 4 children had CSWS and 3
      patients had SIADH. In 2 cases, the cause of hyponatremia was not determined. The
      mean day of hyponatremia after admission was 5.11+/-3.31 days. It was 5.25+/-2.75
      and 5.66+/-7.23 days in children with CSWS and SIADH, respectively. Also, the
      urine sodium (mEq/L) was 190.5+/-73.3 and 58.7+/-43.8 in patients with CSWS and
      SIADH, respectively. CONCLUSION: According to the results of this study, the
      incidence of CSWS was more than SIADH in children with acute CNS disorders. So,
      more attention is needed to differentiate CSWS versus SIADH in order to their
      different management.

PMID- 24665305
TI  - West syndrome in South Iran: electro-clinical manifestations.
AB  - OBJECTIVE: We aimed to determine the clinical and electroencephalographic (EEG)
      characteristics of the patients with West syndrome (WS) in south Iran. MATERIALS
      & METHODS: In this retrospective study, all patients with a clinical diagnosis of
      WS were recruited in the outpatient epilepsy clinic at Shiraz University of
      Medical Sciences between September 2008 and May 2012. Age, gender, age at seizure
      onset, seizure type(s), epilepsy risk factors, EEG and imaging studies of all
      patients were registered routinely. RESULTS: During the study period, 2500
      patients with epilepsy were registered at our epilepsy clinic. Thirty-two
      patients (1.3%) were diagnosed to have WS. Age of onset (mean +/- standard
      deviation) was 4.99 +/- 3.06 months. Sixteen patients were male and 16 were
      female. Nine (28.1%) were reported to have two or more seizure types and 23
      (71.8%) had one seizure type (epileptic spasms). At referral, no developmental
      delay was detected in two patients and in the rest, a mild to severe delay was
      noted. Electroencephalography showed typical hypsarrhythmia in 59.4% of our
      patients and modified hypsarrhythmia or atypical presentations were seen in
      40.6%. Two patients had pyridoxine (B6)-dependent seizures, confirmed by oral B6
      trial. CONCLUSION: Variants of the classical triad of WS including other seizure
      types, atypical EEG findings, and normal psychomotor function at the beginning
      could be observed in some patients. Rarely, treatable genetic disorders (e.g.,
      pyridoxine-dependent seizures) should be considered in those in whom no other
      diagnosis is evident.

PMID- 24665306
TI  - Risk factors for birth asphyxia in an urban health facility in cameroon.
AB  - OBJECTIVE: The World Health Organization (WHO) estimates that 4 million children
      are born with asphyxia every year, of which 1 million die and an equal number
      survive with severe neurologic sequelae. The purpose of this study was to
      identify the risk factors of birth asphyxia and the hospital outcome of affected
      neonates. MATERIALS & METHODS: This study was a prospective case-control study on
      term neonates in a tertiary hospital in Yaounde, with an Apgar score of < 7 at
      the 5th minute as the case group, that were matched with neonates with an Apgar
      score of >= 7 at the 5th minute as control group. Statistical analysis of
      relevant variables of the mother and neonates was carried out to determine the
      significant risk factors. RESULTS: The prevalence of neonatal asphyxia was 80.5
      per 1000 live births. Statistically significant risk factors were the single
      matrimonial status, place of antenatal visits, malaria, pre-eclampsia/eclampsia,
      prolonged labor, arrest of labour, prolonged rupture of membranes, and non
      cephalic presentation. Hospital mortality was 6.7%, that 12.2% of them had
      neurologic deficits and/or abnormal transfontanellar
      ultrasound/electroencephalogram on discharge, and 81.1% had a satisfactory
      outcome. CONCLUSION: The incidence of birth asphyxia in this study was 80.5%
      per1000 live birth with a mortality of 6.7%. Antepartum risk factors were: place
      of antenatal visit, malaria during pregnancy, and preeclampsia/eclampsia. Whereas
      prolonged labor, stationary labor, and term prolonged rupture of membranes were
      intrapartum risk faktors. Preventive measures during prenatal visits through
      informing and communicating with pregnant women should be reinforced.

PMID- 24665307
TI  - Neurological manifestations of an old disease: a case report.
AB  - OBJECTIVE: Neurological manifestations of neonatal disorders have various causes,
      among them neonatal tetanus, albeit rare, is a potentially fatal and preventable
      disease, which is seen in underdeveloped and developing countries. Although the
      disease has been eradicated from I.R. Iran, pregnant women immigrating to Iran
      from neighboring countries, especially from eastern border, may carry a risk of
      neonatal tetanus to the child due to inadequate tetanus immunization and
      inappropriate post-delivery care. It is then important to maintain a high index
      of suspicion for early diagnosis and prompt treatment, when infants present with
      poor feeding and abnormal behavior. Case presentation Here, we report the
      clinical course of a newborn with neonatal tetanus, who was admitted with
      complaints of poor feeding and muscle rigidity, more than a decade after
      eradication of the disorder.

PMID- 24665308
TI  - Mirror movements and myelomeningocele: report of a single case and review of
      literature.
AB  - OBJECTIVE: Mirror movements (MM) have been described in several pathological
      conditions. Their association with neural tube defects is rare, and only 5 cases
      have been reported in literature to date. We report on a case of MM associated
      with cervical myelomeningocele, and we discuss the diffusion tensor imaging
      findings and the underlying mechanism.

PMID- 24665309
TI  - Methylmalonic acidemia: diagnosis and neuroimaging findings of this
      neurometabolic disorder (an Iranian pediatric case series).
AB  - OBJECTIVE: Methylmalonic acidemia is one of the inborn errors of metabolism
      resulting in the accumulation of acylcarnitine in blood and increased urinary
      methylmalonic acid excretion. This disorder can have symptoms, such as
      neurological and gastrointestinal manifestations, lethargy, and anorexia.
      MATERIALS & METHODS: The patients who were diagnosed as methylmalonic acidemia in
      the Neurology Department of Mofid Children's Hospital in Tehran, Iran, between
      2002 and 2012 were included in our study. The disorder was confirmed by clinical
      findings, neuroimaging findings, and neurometabolic and genetic assessment in
      reference laboratory in Germany. We assessed the age, gender, past medical
      history, developmental status, clinical manifestations, and neuroimaging findings
      of 20 patients with methylmalonic acidemia. RESULTS: Eighty percent of the
      patients were offspring of consanguineous marriages. Half of the patients had
      Failure to thrive (FTT) due to anorexia; 85% had history of developmental delay
      or regression, and 20% had refractory seizure, which all of them were controlled.
      The patients with methylmalonic acidemia were followed for approximately 5 years
      and the follow-up showed that the patients with early diagnosis had a more
      favorable clinical response in growth index, refractory seizure, anorexia, and
      neurodevelopmental delay. Neuroimaging findings included brain atrophy, basal
      ganglia involvement (often in putamen), and periventricular leukomalacia.
      CONCLUSION: According to the results of this study, we suggest that early
      assessment and diagnosis have an important role in the prevention of disease
      progression and clinical signs.

PMID- 24665310
TI  - Approach To The First Unprovoked Seizure- PART II.
AB  - The approach to a child who has experienced a first unprovoked generalized tonic
      clonic seizure is challenging and at the same time controversial. How to
      establish the diagnosis, ways and means of investigation and whether treatment is
      appropriate, are different aspects of this subject. In this writing the above
      mentioned matters are discussed. 

PMID- 24665311
TI  - The efficacy and safety of topiramate for prophylaxis of migraine in children.
AB  - OBJECTIVE: Migraine is the most common acute intermittent primary headache in
      children and prophylactic therapy is indicated in children with frequent or
      disabling headaches. The purpose of this study was to evaluate the efficacy and
      safety of topiramate (TPM) for migraine prophylaxis in children. MATERIALS &
      METHODS: In a quasi-experimental study, monthly frequency, severity and duration
      of headache, migraine disability, and side-effects were evaluated in 100 children
      who were referred to the Pediatric Neurology Clinic of Shahid Sadoughi University
      of Medical Sciences, Yazd, Iran from April 2011 to March 2012, and were treated
      with 3 mg/kg/day of TPM for three months. RESULTS: Fifty eight (57.4%) girls and
      42 (41.6%) boys with the mean age of 10.46+/-2.11 years were evaluated. Monthly
      frequency, severity, and duration of headache decreased with treatment from
      15.34+/-7.28 to 6.07+/-3.16 attacks, from 6.21+/-1.74 to 3.15+/-2.22, and from
      2.28+/-1.55 to 0.94+/-0.35 hours, respectively, and the Pediatric Migraine
      Disability Assessment score reduced with TPM from 32.48+/-9.33 to 15.54+/-6.16.
      Transient side-effects were seen in 21% of the patients, including hyperthermia
      in 11%, anorexia and weight loss in 6%, and drowsiness in 4%. No serious side
      effects were reported. CONCLUSION: TPM could be considered as a safe and
      effective drug in pediatric migraine prophylaxis.

PMID- 24665312
TI  - The impacts of hinged and solid ankle-foot orthoses on standing and walking in
      children with spastic diplegia.
AB  - OBJECTIVE: The purpose of this study was to examine the impacts of hinged and
      solid anklefoot orthoses (AFOs) on standing and walking abilities in children
      with spastic diplegia. MATERIALS & METHODS: In a quasi-experimental design, 30
      children with spastic diplegia, aged 4-6 years were recruited. They were matched
      in terms of age, IQ, and level of GMFCS E&R. Children were randomly assigned into
      3 groups: a hinged AFO group (n=10) plus occupational therapy (OT), a solid AFO
      group (n=10) plus OT, a control group who used only OT for three months. Gross
      motor abilities were measured using Gross Motor Measure Function (GMFM). RESULTS:
      We obtained statistically significant differences in the values between baseline
      and after treatment in all groups. The groups were also significantly different
      in total GMFM after intervention. Furthermore, there were differences between
      hinged AFOs and solid AFOs groups, and between hinged AFOs and control groups.
      CONCLUSION: We concluded that gross motor function was improved in all groups;
      however, hinged AFOs group appears to improve the gross motor function better
      than solid AFOs and control groups.

PMID- 24665313
TI  - Zinc status in febrile seizure: a case-control study.
AB  - OBJECTIVE: Febrile seizure is the most common type of seizure in children. Their
      incidence is 2-5%. There are different hypotheses about relationship between
      neurotransmitters and trace elements (such as zinc) and febrile seizure. Zinc, as
      a major element of some enzymes, plays an important role in the central nervous
      system (CNS) and can affect some inhibitory mechanisms of CNS. The aim of the
      present study was to determine whether there were any changes in serum zinc level
      in children with febrile seizure in comparison with febrile children without
      seizure. MATERIALS & METHODS: This case-control study was performed on 100
      patients aged 6 months to 6 years. This study was conducted between January and
      August 2012, on 50 children with febrile seizures (case) and 50 febrile children
      without seizures (control), that were referred to Amirkola Children Hospital (a
      referral hospital in the north of Iran). Two groups were matched for age and sex.
      The serum zinc levels in the both groups were determined by atomic absorption
      spectrophotometry method. RESULTS: The mean serum zinc level was 0.585+/-0.166
      mg/L and 0.704+/-0.179 mg/L in the case group and the control group, respectively
      (p=0.001). The mean serum zinc level was significantly lower in the febrile
      seizure group compared to the control groups. CONCLUSION: Our findings revealed
      that serum zinc level was significantly lower in children with simple febrile
      seizure in comparison with febrile children without seizure. It can emphasize the
      hypothesis that there is a relation between serum zinc level and febrile seizure
      in children.

PMID- 24665314
TI  - Neuroimaging findings in first unprovoked seizures: a multicentric study in
      tehran.
AB  - OBJECTIVE: Seizure is an emergency in pediatrics. It really matters to the
      parents of the involved child to have information about the causes, management
      and prognosis. First unprovoked seizures (FUS) are seizures that occur in
      patients without fever, trauma or infection. Due to the rapid improvement in
      diagnostic techniques in the last few decades, the etiology will be revealed and
      this term will no longer exist. This Study was designed to evaluate brain imaging
      findings in FUS patients. MATERIALS & METHODS: Ninety-six children with FUS, who
      were admitted in three major children's hospitals in Tehran, underwent brain
      imaging and were enrolled into the study. The decision about the type of imaging
      (CT or MRI) was based on the patient's medical and financial conditions. An
      expert radiologist in the field of pediatric neuroimaging interpreted the images.
      RESULTS: Altogether, 27.1% had abnormal findings of which 29.2% were in the brain
      MRI group and 14.3% were in the brain CT scan group. Abnormal results were
      gliosis (10.4%), hemorrhage (4.2%), dysgenesis (2.1%), dysmyelination (7.3%),
      encephalomalacy (1%), atrophy (5.2%) and infarction (2.1%). In some patients, the
      lesions were in 2 or 3 sites and some had more than one type of lesion. There was
      no association between the duration, age and type of seizure and imaging
      abnormlities. However, we found an association between the location of the lesion
      and the type of seizure. CONCLUSION: We recommend brain imaging in all patients
      with FUS and apart from some exceptions, brain MRI is superior to CT.

PMID- 24665315
TI  - Accidental children poisoning with methadone: an Iranian pediatric sectional
      study.
AB  - OBJECTIVE: Toxic poisoning with methadone is common in children in Iran. Our
      study was carried out due to the changing pattern of methadone poisoning in
      recent years and increasing methadone toxicity. MATERIALS & METHODS: In this
      descriptive-sectional study, all of the methadone poisoned children younger than
      12 years who were admitted to the Loghman Hakim Hospital in 2012, were assessed.
      Clinical symptoms and signs, para-clinical findings, and treatment were
      evaluated. RESULTS: In this study, 16 boys and 15 girls who had been poisoned by
      methadone were enrolled. The mean age of patients was 55 months. All patients had
      been poisoned randomly or due to parent's mistakes. The mean time of symptoms
      onset after methadone consumption was 1 hour and 30 Min, indicating a relatively
      long time after onset of symptoms. Clinical findings were drowsiness (75%),
      miotic pupil (68 %), vomiting (61%), rapid shallow breathing (57%) and apnea
      (40%). In paraclinical tests, respiratory acidosis (69%) and leukocytosis (55.2%)
      were seen. The most important finding was increase in distance of QT in ECG
      (23.8%). The mean time of treatment with naloxone infusion was 51 hours. Three
      percent of patients had a return of symptoms after discontinuation of methadone.
      In patients with apnea, a longer course of treatment was required, and this
      difference was significant. Also, 17% of patients with apnea had aspiration
      pneumonia, which was statistically significant. CONCLUSION: We suggest long time
      treatment with naloxone and considering the probability of return of symptoms
      after discontinuation of methadone.

PMID- 24665316
TI  - Relationship between Changes in Serum Sodium Level and Seizures Occurrence in
      Children with Hypernatremic Dehydration.
AB  - OBJECTIVE: To assess any relationship between serum sodium changes and seizure
      occurrence in children aged 2 months to 5 years with hypernatremic dehydration.
      MATERIALS & METHODS: This cross-sectional study was performed on 63 patients aged
      2 months to 5 years from 20 March 2006 to 15 March 2012 at Ghaem Hospital and Dr.
      Sheikh Hospital in Mashhad, Iran. Patients were divided into 2 groups: case group
      with hypernatremic dehydration and seizure occurrence, and control group with
      hypernatremic dehydration and no seizures. RESULTS: The mean age of patients was
      10.38 (2-48) months. Thirteen patients had seizures, 11 out of them, before
      admission and 2 during hospital staying. Serum sodium level at admission in those
      2 patients with seizure occurrence after hospitalization was 169 (158-180)
      mmol/L, and in 50 patients without seizure was 162.8 (148-207) mmol/l. Also, the
      rate of decrease of serum sodium levels in these 2 cases within the first 12
      hours after admission was 1.12, and in those without seizure was 0.54
      (mmol/L/hour), and it was 0.47 and 0.53 (mmol/l/ hour) after 24 hours of
      admission, respectively. Severe dehydration was seen in 38.5% of cases and 14% of
      controls. CONCLUSION: There was not any relationship between changes in serum
      sodium level and seizure occurrence in children with hypernatremic dehydration.

PMID- 24665317
TI  - Neuroimaging in cerebral palsy - report from north India.
AB  - OBJECTIVE: Only few Indian reports exist on neuroimaging abnormalities in
      children with cerebral palsy (CP) from India. MATERIALS & METHODS: We studied the
      clinico-radiological profile of 98 children diagnosed as CP at a tertiary centre
      in North India. Relevant investigations were carried out to determine the
      etiology. RESULTS: Among the 98 children studied, 80.5% were males and 22.2% were
      premature. History of birth asphyxia was present in 41.9%. Quadriplegic CP was
      seen in 77.5%, hemiplegic in 11.5%, and diplegic in 10.5%. Other abnormalities
      were microcephaly (60.5%), epilepsy (42%), visual abnormality (37%), and hearing
      abnormality (20%). Neuroimaging was abnormal in 94/98 (95.91%). Abnormalities
      were periventricular white matter abnormalities (34%), deep grey matter
      abnormalities (47.8%), malformations (11.7%), and miscellaneous lesions (6.4%).
      Neuroimaging findings did not relate to the presence of birth asphyxia, sex,
      epilepsy, gestation, type of CP, or microcephaly. CONCLUSIONS: Neuroimaging is
      helpful for etiological diagnosis, especially malformations.

PMID- 24665318
TI  - Biotinidase deficiency: a reversible neurometabolic disorder (an Iranian
      pediatric case series).
AB  - OBJECTIVE: Biotinidase deficiency is one of the rare congenital metabolic
      disorders with autosomal recessive inheritance. If this disorder is diagnosed in
      newborn period, could be prevented well from mental and physical developmental
      delay and most of clinical manifestations. MATERIALS & METHODS: The patients were
      diagnosed as biotinidase deficiency in Neurology Department of Mofid Children's
      Hospital in Tehran, Iran, between 2009 and 2012 were included in this study. This
      study was conducted to define the age, gender, past medical history,
      developmental status, general appearance, clinical manifestations, neuroimaging
      findings, and response to treatment in 16 patients with biotinidase deficiency in
      this department. RESULTS: In clinical presentation, cutaneous lesions were not
      found in 37% of the patients and 43% patients had not alopecia. 75% patients had
      abnormal neuroimaging that in 56% of them, generalized brain atrophy and
      myelination delay were found. Results of the present study showed the efficacy of
      biotin in early diagnosed patients with seizure and dermatological
      manifestations. The seizure and skin manifestations were improved after biotin
      therapy. CONCLUSION: According to the results of this study, we suggest that
      early assessment and diagnosis have an important role in the prevention of
      disease progression and clinical signs.

PMID- 24665319
TI  - Hypoparathyroidism as the first manifestation of kearns-sayre syndrome: a case
      report.
AB  - OBJECTIVE: Kearns-Sayre syndrome is a mitochondrial myopathy, which was first
      described by Tomas Kearn in 1958. Diagnostic symptoms include retinitis
      pigmentosa, chronic and progressive external ophthalmoplegia plus one or more of
      following factors: heart conduction system disorders, cerebellar ataxia, or
      cerebrospinal fluid (CSF) protein content above 100 mg/dL. The nature of this
      uncommon disease is yet to be clarified. In this paper, we report a case of
      Kearns-Sayre syndrome. According to the previous records, the first manifestation
      of Kearns- Sayre syndrome as hypoparathyroidism is uncommon and in this article,
      we report a case with this problem.

PMID- 24665320
TI  - Downward vertical gaze palsy as a prominent manifestation of episodic ataxia type
      2: a case report.
AB  - OBJECTIVE: Episodic ataxia type 2 (EA2) is an inherited autosomal dominant
      disorder characterized by intermittent ataxia, nausea, vomiting, dysarthria, or
      nystagmus. We report a case of EA2, which downward gaze palsy exists as a common
      sign in all her attacks. Responsiveness of EA2 to acetazolamide was observed in
      this patient.

PMID- 24665321
TI  - Hepatic encephalopathy: early diagnosis in pediatric patients with cirrhosis.
AB  - OBJECTIVE: As acute liver failure (ALF) and chronic liver disease (cirrhosis)
      continue to increase in prevalence, we will see more cases of hepatic
      encephalopathy. Primary care physician are often the first to suspect it, since
      they are familiar with the patient's usual physical and mental status. This
      serious complication typically occurs in patients with severe comorbidities and
      needs multidisciplinary evaluation and care. Hepatic encephalopathy should be
      considered in any patient with acute liver failure and cirrhosis who presents
      with neuropsychiatric manifestations, decrease level of consciousness (coma),
      change of personality, intellectual and behavioral deterioration, speech and
      motor dysfunction. Every cirrhotic patient may be at risk; potential
      precipitating factors should be addressed in regular clinic visits. The
      encephalopathy of liver disease may be prominent, or can be present in subtle
      forms, such as decline of school performance, emotional outbursts, or depression.
      "Subtle form" of hepatic encephalopathy may not be obvious on clinical
      examination, but can be detected by neurophysiologic and neuropsychiatric
      testing.

PMID- 24665322
TI  - Randomised clinical efficacy trial of topiramate and nitrazepam in treatment of
      infantile spasms.
AB  - OBJECTIVE: Infantile spasms (IS) are among the most catastrophic epileptic
      syndromes of infancy. The purpose of this study was to compare efficacy and
      safety of topiramate (TPM) and nitrazepam (NZP) as first-line drugs in the
      treatment of IS. MATERIALS & METHODS: In a parallel single-blinded randomized
      clinical trial, 50 patients with IS referred to Pediatric Neurology Clinic of
      Shahid Sadoughi University of Medical Sciences, Yazd, Iran, were evaluated from
      September 2008 to March 2010. Patients were randomly assigned to two groups to be
      treated with TPM or with NZP for 6 months. The primary endpoint was efficacy in
      cessation of all spasms or reduction of more than 50% in weekly seizure
      frequency, which was evaluated before and 6 months after the drug use. Secondary
      outcome was clinical sideeffects of the drugs. RESULTS: Twenty boys (40%) and 30
      girls (60%) with the mean age of 9.4+/-3.8 months were evaluated. Cessation of
      all spasms occurred in 12 (48%) infants in TPM group and 4(16%) in NZP group.
      Eight (32%) children in TPM group and 7 (28%) in NZP group had more than 50%
      reduction in spasms frequency. So, TPM was more effective. Side effects were seen
      in 32% of TPM and in 36% of NZP groups. CONCLUSION: Topiramate is an effective
      and safe drug, which might be considered as the firstline drug for the treatment
      of ISs.

PMID- 24665323
TI  - The best time for EEG recording in febrile seizure.
AB  - OBJECTIVE: Some studies suggest that detection of epileptic discharge is unusual
      during the first postictal week of febrile seizure and others believe that EEGs
      carried out on the day of the seizure are abnormal in as many as 88% of the
      patients. In this study, we intend to compare early and late EEG abnormalities in
      febrile seizure. MATERIALS & METHODS: EEG was recorded during daytime sleep, 24
      48 hours (early EEG) and 2 weeks (late EEG) after the seizure in 36 children with
      febrile seizure (FS), aged between 3 months and 6 years. EEGs that showed
      generalized or focal spikes, sharp, spike wave complex, and slowing were
      considered as abnormal EEG. Abnormalities of the first EEG were compared with
      those of second EEG. RESULTS: The most common abnormal epileptiform discharges
      recorded in the early EEG were slow waves (27.6%) and sharp waves in late EEG
      (36%). Distribution of abnormalities in early and late EEG showed no significant
      statistical difference. CONCLUSION: The early and late EEG recording had the same
      results in patient with febrile seizure.

PMID- 24665324
TI  - Use of complementary and alternative medicine for epileptic children in tehran: a
      cross-sectional study (2009-2011).
AB  - OBJECTIVE: Although the use of Complementary and Alternative Medicine (CAM) has
      been evaluated globally, there are few studies in our country on this subject.
      The purpose of this study was to determine the prevalence, pattern of use,
      parental sources of information, and benefits of CAM in epileptic children in
      Tehran. MATERIALS & METHODS: One hundred thirty-three parents or relatives of
      epileptic children who were referred to outpatient clinics or admitted in
      neurologic ward of four major hospitals in Tehran, were interviewed by our
      researcher based on a structured questionnaire; from 2009 to 2010. The
      information obtained comprised the demographic data of patients and their
      parents, frequency and morphology of convulsions, the type and sources of CAM and
      finally, the benefits and adverse effects of this practice. RESULTS: Forty-four
      percent of the respondents had used CAM methods either alone or in combination
      with other methods. The most frequently used CAM was written prayers followed by
      oral herbs and special diets. CAM was mainly introduced to them by relatives.
      Only 16.7% of these parents had discussed this matter with their children's
      physicians. No efficacy to control seizure was observed for most of these
      methods. CONCLUSION: This study showed that use of CAM in our study group is
      relatively common and may have a potentially hazardous role in the treatment
      process. So, it is necessary for physicians to have enough information about CAM
      practice in their patients.

PMID- 24665325
TI  - Novel Point Mutations in Frataxin Gene in Iranian Patients with Friedreich's
      Ataxia.
AB  - OBJECTIVE: Friedreich's ataxia is the most common form of hereditary ataxia with
      autosomal recessive pattern. More than 96% of patients are homozygous for GAA
      repeat extension on both alleles in the first intron of FXN gene and the
      remaining patients have been shown to be heterozygous for a GAA extension in one
      allele and point mutation in other allele. MATERIALS & METHODS: In this study,
      exons of 1, 2, 3, and 5 of frataxin gene were searched by single strand
      conformation polymorphism polymerase chain reaction (PCR-SSCP) in 5 patients with
      GAA extension in one allele. For detection of exact mutation, samples with band
      shifts were sent for DNA sequencing. RESULTS: Three novel point mutations were
      found in patients heterozygous for the GAA repeat expansion, p.S81A, p.Y123D, and
      p.S192C. CONCLUSION: Our results showed that these point mutations in one allele
      with GAA extension in another allele are associated with FRDA signs. Thus, these
      results emphasize the importance of performing molecular genetic analysis for
      point mutations in FRDA patients.

PMID- 24665326
TI  - The effects of imitative vs. Cognitive methods on the speech development of
      children with autism.
AB  - OBJECTIVE: The present study was performed to examine the effects of two speech
      therapy methods on six verbal behaviors of autistic children, including oral
      speech, listening, organizing, speaking, semantics, and syntax. MATERIALS &
      METHODS: IN THIS STUDY, THIRTY CHILDREN WITH AUTISM WERE ASSIGNED TO ONE OF TWO
      GROUPS: imitative and cognitive groups. Before starting the main procedures of
      the study, the children of both groups were homogenized concerning their autism
      level. In the first phase of the study, the speech development level of the two
      groups was measured in a pre-test, in which both groups showed similar results.
      Then, both groups of children received 6 months of speech therapy instruction,
      during which one group was taught using an imitative method, while the other
      group was being worked with cognitive method. RESULTS: After 6-month treatment
      period, a post-test was done, and the t-tests based on the data of the two groups
      revealed a significant difference between the results. CONCLUSION: The statistics
      showed that after the teaching period, autistic that worked with cognitive method
      gained a better development in their speech abilities, comparing to those worked
      with the imitative method.

PMID- 24665328
TI  - Evaluation of the effects of psychotherapy on anxiety among mothers of children
      with leukemia.
AB  - OBJECTIVE: Children with leukemia and their families face a long period of
      medical treatment and uncertainty about the future. These families may suffer
      from short- and long-term emotional problems. The aim of the present study was to
      assess the effect of supportive psychotherapy on the anxiety of mothers whose
      children suffer from leukemia. MATERIALS & METHODS: The current research were
      performed on mothers who had a child with leukemia hospitalized in Mofid
      Children's Hospital, Tehran, Iran. They were randomly selected. The research
      method was a quasi-experimental study with pretest/posttest design. The pretest
      Kettles' anxiety questionnaire was given to all the mothers and after seven
      sessions of supportive psychotherapy, the posttest was performed and the grades
      were compared. RESULTS: Ten mothers finished all seven therapeutic sessions.
      There was a statistically significant difference between the pretest and posttest
      mean scores, confirming the mothers' reduced anxiety level. CONCLUSION: Finding
      effective and newer approaches to improve the well-being of parents with a sick
      child is an important challenge of today's medical researches. Based on our
      findings, it is possible to reduce the anxiety in mothers of children with
      leukemia through supportive psychiatric therapies. KEYWORDS: Leukemia; Mothers;
      Anxiety; Psychology; Child.

PMID- 24665327
TI  - Screening for depression in hospitalized pediatric patients.
AB  - OBJECTIVE: In chronically ill children who are hospitalized, many mood changes
      occur. For example, in children with cancer or renal failure, prolonged
      hospitalization and chemotherapy can lead to depression. With the improved
      survival of childhood malignancies, the effect of treatment on child's
      psychosocial well-being becomes increasingly relevant. In this study, we examined
      the prevalence of depression in hospitalized children with chronic and acute
      conditions in Dr Sheikh Pediatrics Hospital in Mashhad. MATERIALS & METHODS:
      After receiving the approval from the Ethics Committee of Mashhad University of
      Medical Sciences, we did this cross-sectional descriptive study, from April to
      June 2012 in Dr Sheikh Pediatric Hospital in Mashhad. Ninety children, between 8
      to 16 years, were screened for depression. The sampling method was census.
      Children with a history of depressive or other mental disorders were excluded.
      Three groups of children (children with chronic renal disease, malignancy, and
      acute disease) were evaluated for depression using standard Children Depression
      Inventory Questionnaire (CDI). Two specifically trained nurses filled out the
      questionnaires at patients' bedside under the supervision of a psychiatrist.
      Depression scores were then analyzed by SPSS software. RESULTS: Of 90 children,
      43(47.7%) were male and 47(52.2%) were female. The Children's mean age was 11+/
      2.3 years, and the mean length of hospitalization was 8+/-5.3 days. Depression
      was detected in various degrees in 63% of patients (N=57), and 36.6% of children
      (N=32) had no symptoms of depression. Severe depression was not seen in any of
      the patients with acute illness. More than half of patients with cancer and
      chronic kidney disease had moderate to severe depression. There was a significant
      statistical relationship between the duration of illness and severity of
      depression. There was also a significant correlation between severity of
      depression and frequency of hospitalization. Children who had been hospitalized
      more than 3 times in the previous year, experienced more severe levels of
      depression. We also found a significant correlation between pubertal age and
      severity of depression in patients with cancers and chronic renal failure.
      CONCLUSION: Children who are hospitalized due to chronic conditions are at a
      higher risk for mood disorders in comparison with the ones with acute conditions.
      It is therefore advisable to consider more practical plans to improve the care
      for hospitalized children's mental health.

PMID- 24665329
TI  - Propionic acidemia: diagnosis and neuroimaging findings of this neurometabolic
      disorder.
AB  - OBJECTIVE: Propionic acidemia is one of the rare congenital neurometabolic
      disorders with autosomal recessive inheritance. This disorder is caused by a
      defect in the propionyl-CoA carboxylase enzyme and can be presented with life
      threatening ketoacidosis, lethargy, failure to thrive, and developmental delay.
      MATERIALS & METHODS: The patients diagnosed as having propionic acidemia in
      Neurology Department of Mofid Children's Hospital in Tehran, Iran, between 2002
      and 2012 were include in our study. This disorder was confirmed by clinical
      manifestations, neuroimaging findings, and neurometabolic assessment in the
      reference laboratory in Germany. Our study was conducted to define the sex, age,
      gender, past medical history, developmental status, clinical findings, and
      neuroimaging manifestations in 10 patients with propionic acidemia. RESULTS:
      Seventy percent of patients were offspring of consanguineous marriages. In this
      study, only one patient had microcephaly at birth, but at detection time, 30% of
      patients had head circumference and weight below the 3rd percentile. The patients
      were followed for approximately 5 years and this follow-up showed that the
      patients with early diagnosis had a more favorable clinical response.
      Neuroimaging findings included brain atrophy, white matter and globus pallidus
      involvement. CONCLUSION: Finally we suggest that early diagnosis and treatment
      have an important role in the prevention of disease progression.

PMID- 24665331
TI  - Vincristine-induced cranial neuropathy.
AB  - Vincristine (VCR) is a vinca alkaloid that is used for treatment of many
      malignancies. The vinca alkaloids are neurotoxic, usually causing a peripheral
      neuropathy, but cranial neuropathies are rare as side effects. Described here is
      the case of a 2.5-year-old boy, a known case of Wilms' tumor, treated by
      vincristine (0.067 mg/kg/day) and dactinomycin (0.045 mg/kg/day) after surgery.
      Three weeks after treatment, he presented with bilateral ptosis. Neurological
      examination revealed bilateral ptosis with normal pupillary reflex and eye
      movement. He received 3.015 mg cumulative dose of vincristine before development
      of ptosis. Treatment with pyridoxine (150 mg/m2 p.o. BID) and pyridostigmine (3
      mg/kg p.o. BID) was started as neuroprotective agents, and after 7 days the
      problem disappeared. The treatment continued for 6 weeks and there were no signs
      of ptosis or a recurrence in follow up 2 months later. 

PMID- 24665330
TI  - Neuropsychiatric Symptoms as The First Manifestation of Juvenile Systemic Lupus
      Erythematosus: A Complicated Case with Klinefelter's Syndrome.
AB  - Systemic Lupus Erythematosus (SLE) is an autoimmune, multisystem disorder with
      various manifestations. There are limited reports on the neuropsychiatric
      findings as the first manifestation of SLE in children. Herein, we report a 14
      year-old Iranian boy with a two-year history of cognitive dysfunction and
      behavioural problems as well as a recent history of epistaxis. The patient workup
      ended with a diagnosis of Klinefelter's syndrome associated with juvenile SLE.
      Patients with Klinefelter's syndrome may exhibit behavioural problems and
      psychological disease. These psychiatric disorders could be complicated with
      lupus in children. In fact, psychiatric symptoms may occur as the first
      manifestation of juvenile SLE. Specially, if accompanied with Klinefelter's
      syndrome. We suggest the diagnosis of SLE must be considered in all children with
      neuropsychiatric manifestations. 

PMID- 24665332
TI  - Guillain-barre syndrome presenting with bilateral facial nerve palsy.
AB  - OBJECTIVE: This case study is about an 11-year-old girl with bilateral facial
      weakness, abnormal taste sensation, and absent deep tendon reflexes of both knees
      and ankles. However, the muscle power of the lower and upper extremities across
      all muscle groups was normal. After 2 days, she developed paresthesia and
      numbness in the lower extremities. Other neurologic examinations, such as
      fundoscopic evaluation of the retina were normal with the muscle power of both
      upper- and lower-extremities intact. A lumbar puncture revealed
      albumincytological dissociation. EMG and NCV were in favor of Guillain-Barre
      syndrome, for which IVIG was prescribed and the abnormal sensations in the lower
      limbs rapidly improved. Bilateral facial diplegia without weakness and
      paresthesia is a variant of Guillain-Barre syndrome that mostly presents with
      acute onset, rapid progression with or without limb weakness, paresthesia, and
      decreased or absent DTR and albumin-cytological dissociation.

PMID- 24665333
TI  - Deqi sensation in different kinds of acupuncture.

PMID- 24665334
TI  - The Effect of Acupuncture to SP6 on Skin Temperature Changes of SP6 and SP10: An
      Observation of "Deqi".
AB  - Background. Deqi sensation is a complex but an important component for
      acupuncture effect. In this study, we tried to observe the relationship between
      Deqi and skin temperature changes and whether there was some relativity between
      Deqi and needle stimulations on cold congealing and dysmenorrhea rat model.
      Thirty-two female Sprague Dawley (SD) rats were randomly divided into four groups
      (Saline Control Group, Model Group, Group A with strong stimulation, and Group B
      with small stimulation). Group A and Group B were performed with different
      stimulations. We found that, compared with saline control group, model group, and
      Group B, Group A showed that the skin temperature changes on right acupoint SP6
      and SP10 increased significantly at 5 min-10 min interval. The skin temperature
      changes on left SP6 decreased at instant-5 min interval. The skin temperature
      changes on right SP10 decreased significantly at instant-5 min interval and 10
      min-20 min interval. Thermogenic action along Spleen Meridian of Foot Greater Yin
      was manifested as simultaneous skin temperature increase on right SP6 and SP10 at
      5 min-10 min interval after needling SP6, which was helpful to illustrate the
      relationship between the characteristic of Deqi and needle stimulations. 

PMID- 24665336
TI  - Research highlights for issue 3.

PMID- 24665335
TI  - Protective Effect of Solanum nigrum Leaves Extract on Immobilization Stress
      Induced Changes in Rat's Brain.
AB  - The prophylactic or curative antioxidant efficacy of crude extract and the active
      constituent of S. nigrum leaves were evaluated in modulating inherent antioxidant
      system altered due to immobilization stress in rat brain tissues, in terms of
      measurement of glutathione (GSH), lipid peroxidation (thiobarbituric acid
      reactive substances, TBARS), and free radical scavenging enzymes activities. Rats
      were treated with single dose of crude extract of S. nigrum prior to and after 6
      h of immobilization stress exposure. Exposure to immobilization stress resulted
      in a decrease in the brain levels of glutathione, SOD, GST, and catalase, with an
      increase in thiobarbituric acid reactive substances (TBARS) levels. Treatment of
      S. nigrum extract and its active constituents to both pre- and poststressed rats
      resulted in significant modulation in the above mentioned parameters towards
      their control values with a relative dominance by the latter. Brain is vulnerable
      to stress induced prooxidant insult due to high levels of fat content. Thus, as a
      safe herbal medication the S. nigrum leaves extract or its isolated constituents
      can be used as nutritional supplement for scavenging free radicals generated in
      the brain due to physical or psychological stress or any neuronal diseases per
      se. 

PMID- 24665337
TI  - Time-series analysis reveals genetic responses to intensive management of
      razorback sucker (Xyrauchen texanus).
AB  - Time-series analysis is used widely in ecology to study complex phenomena and may
      have considerable potential to clarify relationships of genetic and demographic
      processes in natural and exploited populations. We explored the utility of this
      approach to evaluate population responses to management in razorback sucker, a
      long-lived and fecund, but declining freshwater fish species. A core population
      in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for
      decades and is maintained by harvesting naturally produced larvae from the lake,
      rearing them in protective custody, and repatriating them at sizes less
      vulnerable to predation. Analyses of mtDNA and 15 microsatellites characterized
      for sequential larval cohorts collected over a 15-year time series revealed no
      changes in geographic structuring but indicated significant increase in mtDNA
      diversity for the entire population over time. Likewise, ratios of annual
      effective breeders to annual census size (N b /N a) increased significantly
      despite sevenfold reduction of N a. These results indicated that conservation
      actions diminished near-term extinction risk due to genetic factors and should
      now focus on increasing numbers of fish in Lake Mohave to ameliorate longer-term
      risks. More generally, time-series analysis permitted robust testing of trends in
      genetic diversity, despite low precision of some metrics. 

PMID- 24665338
TI  - Genotyping by sequencing resolves shallow population structure to inform
      conservation of Chinook salmon (Oncorhynchus tshawytscha).
AB  - Recent advances in population genomics have made it possible to detect previously
      unidentified structure, obtain more accurate estimates of demographic parameters,
      and explore adaptive divergence, potentially revolutionizing the way genetic data
      are used to manage wild populations. Here, we identified 10 944 single-nucleotide
      polymorphisms using restriction-site-associated DNA (RAD) sequencing to explore
      population structure, demography, and adaptive divergence in five populations of
      Chinook salmon (Oncorhynchus tshawytscha) from western Alaska. Patterns of
      population structure were similar to those of past studies, but our ability to
      assign individuals back to their region of origin was greatly improved (>90%
      accuracy for all populations). We also calculated effective size with and without
      removing physically linked loci identified from a linkage map, a novel method for
      nonmodel organisms. Estimates of effective size were generally above 1000 and
      were biased downward when physically linked loci were not removed. Outlier tests
      based on genetic differentiation identified 733 loci and three genomic regions
      under putative selection. These markers and genomic regions are excellent
      candidates for future research and can be used to create high-resolution panels
      for genetic monitoring and population assignment. This work demonstrates the
      utility of genomic data to inform conservation in highly exploited species with
      shallow population structure. 

PMID- 24665339
TI  - Quantitative resistance can lead to evolutionary changes in traits not targeted
      by the resistance QTLs.
AB  - This paper addresses the general concern in plant pathology that the introduction
      of quantitative resistance in the landscape can lead to increased pathogenicity.
      Hereto, we study the hypothetical case of a quantitative trait loci (QTL) acting
      on pathogen spore production per unit lesion area. To regain its original
      fitness, the pathogen can break the QTL, restoring its spore production capacity
      leading to an increased spore production per lesion. Or alternatively, it can
      increase its lesion size, also leading to an increased spore production per
      lesion. A data analysis shows that spore production per lesion (affected by the
      resistance QTL) and lesion size (not targeted by the QTL) are positively
      correlated traits, suggesting that a change in magnitude of a trait not targeted
      by the QTL (lesion size) might indirectly affect the targeted trait (spore
      production per lesion). Secondly, we model the effect of pathogen adaptation
      towards increased lesion size and analyse its consequences for spore production
      per lesion. The model calculations show that when the pathogen is unable to
      overcome the resistance associated QTL, it may compensate for its reduced fitness
      by indirect selection for increased pathogenicity on both the resistant and
      susceptible cultivar, but whereby the QTLs remain effective. 

PMID- 24665340
TI  - Hybridization of an invasive shrub affects tolerance and resistance to
      defoliation by a biological control agent.
AB  - Evolution has contributed to the successful invasion of exotic plant species in
      their introduced ranges, but how evolution affects particular control strategies
      is still under evaluation. For instance, classical biological control, a common
      strategy involving the utilization of highly specific natural enemies to control
      exotic pests, may be negatively affected by host hybridization because of shifts
      in plant traits, such as root allocation or chemical constituents. We
      investigated introgression between two parent species of the invasive shrub
      tamarisk (Tamarix spp.) in the western United States, and how differences in
      plant traits affect interactions with a biological control agent. Introgression
      varied strongly with latitude of origin and was highly correlated with plant
      performance. Increased levels of T. ramosissima introgression resulted in both
      higher investment in roots and tolerance to defoliation and less resistance to
      insect attack. Because tamarisk hybridization occurs predictably on the western
      U.S. landscape, managers may be able to exploit this information to maximize
      control efforts. Genetic differentiation in plant traits in this system underpins
      the importance of plant hybridization and may explain why some biological control
      releases are more successful than others. 

PMID- 24665341
TI  - Exposure to phages has little impact on the evolution of bacterial antibiotic
      resistance on drug concentration gradients.
AB  - The use of phages for treating bacterial pathogens has recently been advocated as
      an alternative to antibiotic therapy. Here, we test a hypothesis that bacteria
      treated with phages may show more limited evolution of antibiotic resistance as
      the fitness costs of resistance to phages may add to those of antibiotic
      resistance, further reducing the growth performance of antibiotic-resistant
      bacteria. We did this by studying the evolution of phage-exposed and phage-free
      Pseudomonas fluorescens cultures on concentration gradients of single drugs,
      including cefotaxime, chloramphenicol, and kanamycin. During drug treatment, the
      level of bacterial antibiotic resistance increased through time and was not
      affected by the phage treatment. Exposure to phages did not cause slower growth
      in antibiotic-resistant bacteria, although it did so in antibiotic-susceptible
      bacteria. We observed significant reversion of antibiotic resistance after drug
      use being terminated, and the rate of reversion was not affected by the phage
      treatment. The results suggest that the fitness costs caused by resistance to
      phages are unlikely to be an important constraint on the evolution of bacterial
      antibiotic resistance in heterogeneous drug environments. Further studies are
      needed for the interaction of fitness costs of antibiotic resistance with other
      factors. 

PMID- 24665342
TI  - Inferring influenza global transmission networks without complete phylogenetic
      information.
AB  - Influenza is one of the most severe respiratory infections affecting humans
      throughout the world, yet the dynamics of its global transmission network are
      still contentious. Here, I describe a novel combination of phylogenetics, time
      series, and graph theory to analyze 14.25 years of data stratified in space and
      in time, focusing on the main target of the human immune response, the
      hemagglutinin gene. While bypassing the complete phylogenetic inference of huge
      data sets, the method still extracts information suggesting that waves of genetic
      or of nucleotide diversity circulate continuously around the globe for subtypes
      that undergo sustained transmission over several seasons, such as H3N2 and
      pandemic H1N1/09, while diversity of prepandemic H1N1 viruses had until 2009 a
      noncontinuous transmission pattern consistent with a source/sink model.
      Irrespective of the shift in the structure of H1N1 diversity circulation with the
      emergence of the pandemic H1N1/09 strain, US prevalence peaks during the winter
      months when genetic diversity is at its lowest. This suggests that a dominant
      strain is generally responsible for epidemics and that monitoring genetic and/or
      nucleotide diversity in real time could provide public health agencies with an
      indirect estimate of prevalence. 

PMID- 24665343
TI  - Hybridization increases invasive knotweed success.
AB  - Hybridization is one of the fundamental mechanisms by which rapid evolution can
      occur in exotic species. If hybrids show increased vigour, this could
      significantly contribute to invasion success. Here, we compared the success of
      the two invasive knotweeds, Fallopia japonica and F. sachalinensis, and their
      hybrid, F. * bohemica, in competing against experimental communities of native
      plants. Using plant material from multiple clones of each taxon collected across
      a latitudinal gradient in Central Europe, we found that knotweed hybrids
      performed significantly better in competition with a native community and that
      they more strongly reduced the growth of the native plants. One of the parental
      species, F. sachalinensis, regenerated significantly less well from rhizomes, and
      this difference disappeared if activated carbon was added to the substrate, which
      suggests allelopathic inhibition of F. sachalinensis regeneration by native
      plants. We found substantial within-taxon variation in competitive success in all
      knotweed taxa, but variation was generally greatest in the hybrid. Interestingly,
      there was also significant variation within the genetically uniform F. japonica,
      possibly reflecting epigenetic differences. Our study shows that invasive
      knotweed hybrids are indeed more competitive than their parents and that
      hybridization increased the invasiveness of the exotic knotweed complex. 

PMID- 24665344
TI  - Local adaptation and the potential effects of a contaminant on predator avoidance
      and antipredator responses under global warming: a space-for-time substitution
      approach.
AB  - The ability to deal with temperature-induced changes in interactions with
      contaminants and predators under global warming is one of the outstanding,
      applied evolutionary questions. For this, it is crucial to understand how
      contaminants will affect activity levels, predator avoidance and antipredator
      responses under global warming and to what extent gradual thermal evolution may
      mitigate these effects. Using a space-for-time substitution approach, we assessed
      the potential for gradual thermal evolution shaping activity (mobility and
      foraging), predator avoidance and antipredator responses when Ischnura elegans
      damselfly larvae were exposed to zinc in a common-garden warming experiment at
      the mean summer water temperatures of shallow water bodies at southern and
      northern latitudes (24 and 20 degrees C, respectively). Zinc reduced mobility and
      foraging, predator avoidance and escape swimming speed. Importantly, high
      latitude populations showed stronger zinc-induced reductions in escape swimming
      speed at both temperatures, and in activity levels at the high temperature. The
      latter indicates that local thermal adaptation may strongly change the ecological
      impact of contaminants under global warming. Our study underscores the critical
      importance of considering local adaptation along natural gradients when
      integrating biotic interactions in ecological risk assessment, and the potential
      of gradual thermal evolution mitigating the effects of warming on the
      vulnerability to contaminants. 

PMID- 24665346
TI  - Serum endocan as a novel prognostic biomarker in patients with hepatocellular
      carcinoma.
AB  - Endocan is a vascular endothelium-derived factor regulated by angiogenic factors.
      The aim of this study was to determine whether serum endocan levels are
      prognostic for survival in patients with hepatocellular carcinoma (HCC). Serum
      endocan levels were measured in 64 HCC patients who were naive to treatment,
      eight apparently healthy subjects, and 68 patients with liver cirrhosis; the
      latter two groups served as controls. Prognostic factors for the survival of HCC
      patients were examined using a Cox proportional hazards model. The median serum
      endocan levels were 1.145 ng/mL (range, 0.93-1.68 ng/mL) in healthy subjects,
      1.93 ng/mL (range, 0.45-8.47 ng/mL) in liver cirrhosis patients, and 3.73 ng/mL
      (range, 0.74-10.95 ng/mL) in HCC patients (P = 0.0001). In HCC patients, elevated
      serum endocan levels were significantly associated with poor hepatic function (P
      = 0.015), a greater number of tumors (P = 0.034), and vascular invasion (P =
      0.043). The median follow-up period was 23.0 months, and 33 HCC patients died
      during follow up. Multivariate analysis showed that serum endocan levels >= 2.20
      ng/mL (hazard ratio 2.36, 95% confidence interval 1.22-5.36, P = 0.008) as well
      as elevated serum alpha-fetoprotein and des-gamma-carboxy prothrombin levels were
      independent prognostic biomarkers for poor survival. The combination of serum
      endocan and these two additional markers was significantly predictive of worse
      survival (P < 0.0001). Thus, serum endocan may be a prognostic biomarker for
      survival in HCC patients, and the combination of serum endocan, alpha
      fetoprotein, and des-gamma-carboxy prothrombin levels can result in better
      prognostic stratification of these patients. 

PMID- 24665347
TI  - Cone Beam Computertomography (CBCT) in Interventional Chest Medicine - High
      Feasibility for Endobronchial Realtime Navigation.
AB  - INTRODUCTION: Currently there are several advanced guiding techniques for
      pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN):
      Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS)
      with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the
      pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom
      if ever used) endobronchial or (common) transthoracical approach. In several
      situations one technique is not enough for efficient diagnosis, therefore we
      investigated a new diagnostic technique of endobronchial guided biopsies by a
      Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim,
      Germany). METHOD AND MATERIAL: In our study 33 incidental solitary pulmonary
      nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest
      distance to pleura 25+/-18mm) were eligible according to in- and exclusion
      criteria. Realtime and onsite navigation were performed according to our standard
      protocol.22 All iSPN were controlled with a second technique when necessary and
      clinical feasible in case of unspecific or unexpected histological result. In all
      cases common guidelines of treatment of different iSPNs were followed in a
      routine manner. RESULTS: Overall navigational yield (ny) was 91% and diagnostic
      yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the
      subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean
      diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe
      a significant difference in specifity of biopsy results in regards to the
      position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the
      whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but
      inside the outer one third of an iSPN-3DV with the specifity of biopsies of
      centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a
      significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for
      centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered
      biopsies should be relied on especially in case of a benign result. CONCLUSION:
      The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB)
      only with forceps is at least up to twofold higher than conventional TBB for
      iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in
      invisible SPNs is at least in the range of other navigation studies which were
      performed partly with multiple navigation tools and multiple instruments. For
      future diagnostic and therapeutic approaches it is so far the only onsite and
      realtime extrathoracic navigation approach (except for computed tomography (CT)
      fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The
      system purchase represents an important investment for hospitals but it is a
      multidisciplinary and multinavigational tool with possible access via bronchial
      airways, transthoracical or vascular approach at the same time and on the same
      table without the need for an expensive disposable instrument use.

PMID- 24665348
TI  - Relationship between Serum Level of Lymphatic Vessel Endothelial Hyaluronan
      Receptor-1 and Prognosis in Patients with Lung Cancer.
AB  - BACKGROUND: Lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) is a
      hyaluronic acid receptor that is selectively expressed in the endothelia of
      lymphatic capillaries. The density of lymphatic vessels expressing LYVE-1 on
      immunohistochemistry negatively correlates with prognosis of patients with non
      small-cell lung cancer. However, the relationship between LYVE-1 serum levels and
      lung cancer staging is unknown. METHODS: We collected blood samples from 58 lung
      cancer patients before treatment and measured LYVE-1 serum levels using an enzyme
      linked immunosorbent assay. RESULTS: Mean serum LYVE-1 levels were 1,420 pg/mL.
      Serum LYVE-1 levels correlated positively with serum albumin levels, but
      inversely with primary tumor size, leukocyte counts, and platelet counts by
      Pearson's product-moment correlation coefficient. A high cancer staging,
      occurrence of lymph-node metastases, and occurrence of distant metastases were
      significantly associated with low LYVE-1 levels. Moreover, multiple logistic
      regression analyses revealed that LYVE-1 levels were predictive of the presence
      of lymph node and distant metastases, independently of the other factors. Kaplan
      Meier analysis showed that the survival of patients with serum LYVE-1 <=1,553
      pg/mL was significantly poorer than that of patients with serum LYVE-1 >1,553
      pg/mL. This survival difference relative to LYVE-1 levels remained statistically
      significant after adjusting for age and gender by the Cox proportional-hazard
      analysis. CONCLUSION: Serum LYVE-1 is significantly low in lung cancer patients
      with metastasis, compared with those without. Measuring LYVE-1 levels in lung
      cancer patients may be useful for evaluating lung cancer progression.

PMID- 24665349
TI  - Partial Response at Completion of Bortezomib-Thalidomide-Dexamethasone (VTd)
      Induction Regimen Upfront in Multiple Myeloma Does Not Preclude Response to VTd
      in Consolidation.
AB  - The impact of consolidation on response rates and PFS has recently been
      demonstrated after induction and autotransplantation upfront in Multiple Myeloma
      (MM). We further showed that patients in >=VGPR following the intensification
      procedure benefited most from consolidation. Question remains as to the benefit
      of consolidation for patients in PR at completion of induction - feature of
      partial resistance to the induction regimen. We collected data from 54 newly
      diagnosed MM treated with VTd-auto-VTd regimen that reached only PR at completion
      of the induction procedure. Overall, 37 patients (68%) improved depth of response
      (>=VGPR) at completion of consolidation, including 35% that reached CR and 38%
      solely related to consolidation. Of patients that remained on PR or improved
      depth of response after ASCT, 26% and 38% further responded to consolidation,
      respectively. With a median follow-up of 36 months, improved depth of response
      translated into lower relapse rate compared with patients remaining in PR, 19%
      vs. 36%. This difference was more striking in patients that reached CR vs.
      others, 8% and 38%, respectively (p=0.039). The median TTP was prolonged in
      patients that improved depth of response after consolidation (p=0.012), with a 3
      year TTP of 87% vs. 18% otherwise. In multivariate analysis, lack of improved
      depth of response to consolidation independently predicted shorten median TTP
      [OR=4.4, 95%CI=1-21; p=0.039], with elevated LDH and beta2m, and adverse FISH.
      This study shows that VTd consolidation should be recommended to patients solely
      on PR at completion of induction with VTd, feature of lower sensitivity to VTd. 

PMID- 24665351
TI  - The effect of concomitant cardiac resynchronization therapy on quality of life in
      patients with heart failure undergoing cardiac surgery.
AB  - OBJECTIVES: To evaluate the effect of concomitant cardiac resynchronization
      therapy (CRT) on health related quality of life (QoL) in patients with heart
      failure (HF) and ventricular dyssynchrony undergoing cardiac surgery. METHODS:
      Twenty-eight patients received permanent epicardial CRT in connection to coronary
      artery bypass grafting (CABG) and/or aortic valve replacement (AVR) (CRT group).
      Thirty-seven HF patients without concomitant CRT served as a comparison group
      (non-CRT group). SF-36 was used to assess QoL in the two groups and was also
      compared with the general Swedish population. RESULTS: The median follow-up time
      was 28 months after surgery (range 8 to 44 months). No difference in QoL could be
      shown between the CRT group and the comparison group. Several subscales of QoL in
      the CRT group were in range with the general Swedish population. CONCLUSION:
      Concomitant CRT for patients with HF and ventricular dyssynchrony undergoing CABG
      and/or AVR did not result in a higher estimated QoL compared to HF patients
      without CRT.

PMID- 24665350
TI  - Association between APE1 Single Nucleotide Polymorphism (rs1760944) and Cancer
      Risk: a Meta-Analysis Based on 6,419 Cancer Cases and 6,781 Case-free Controls.
AB  - Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base
      excision repair pathway. Epidemiological studies have suggested associations
      between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to
      evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We
      searched Pubmed, ISI Web of Knowledge, Embase, Chinese National Knowledge
      Infrastructure (CNKI) databases until September 2013 to identify eligible
      studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to
      estimate the strength of the associations. 12 studies from 11 articles on APE1
      rs1760944 genotypes and cancer risk were identified, including a total of 6,419
      cancer cases and 6,781 case-free controls. Overall, APE1 rs1760944 polymorphism
      was significantly associated with the decreased risk of cancer in any genetic
      models (G vs. T: OR = 0.86, 95% CI = 0.82-0.90; homozygote comparison: OR = 0.74,
      95% CI = 0.67-0.82; heterozygote comparison: OR =0.88, 95%CI = 0.81-0.95;
      dominant model TG+GG vs. TT: OR = 0.82, 95% CI = 0.76-0.89; recessive model GG
      vs. TT+TG: OR = 0.81, 95%CI = 0.75-0.88). In the stratified analysis by
      populations, the effect was remain in studies of Asian population (homozygote
      comparison: OR = 0.71, 95%CI = 0.63-0.79; heterozygote comparison: OR = 0.86, 95
      %CI = 0.79- 0.94; dominant model: OR = 0.80, 95% CI = 0.74 -0.87 and recessive
      model: OR = 0.78, 95%CI = 0.71-0.86). Moreover, a significantly decreased risk
      was found in lung cancer studies (homozygote comparison: OR = 0.68, 95% CI = 0.59
      0.79; heterozygote comparison: OR = 0.86, 95%CI = 0.77- 0.98; dominant model: OR
      = 0.80, 95%CI = 0.72-0.90 and recessive model: OR= 0.77, 95% CI= 0.68-0.87).
      These findings support that APE1 rs1760944 polymorphism has a possible protective
      effect on cancer susceptibility particularly among Asians. Further studies based
      on different ethnicity and various cancer types are warranted to verify our
      findings. 

PMID- 24665352
TI  - Resilience and treatment adhesion in patients with systemic lupus erythematosus.
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune, rheumatic
      inflammatory disease that can cause significant morbidity with evident
      psychological impacts and obvious harm to quality-of-life that require the
      patient to adapt treatment. OBJECTIVE: Assessment of resilience and the self
      reported treatment adhesion behaviors of patients with SLE, investigating which
      of these factors are associated to resilience. METHOD: Cross-sectional study of
      40 women with SLE. A questionnaire with social demographic data, health history
      and the Wagnild Young Resilience Scale were used. RESULTS: 62.5% followed the
      medical treatment properly but 55% found it difficult. 27.5% of the patients
      presented low resilience, 57.5% medium and 15% high resilience. Resilience was
      associated in the chi-square test (p-value < 0.05) with the variables work,
      understanding SLE, trying to find out about SLE, following the treatment
      correctly, difficulty in following the treatment and stopping some activity
      because of the disease. In the correlation analysis, resilience was associated
      with age (-0.3960), number of working hours (0.5533), specialized treatment
      duration (-0.8103) and disease duration from diagnosis (-0.8014). CONCLUSION:
      Patients with high resilience tended to follow treatment correctly, tried to
      understand the disease and adhered more to the treatment to avoid risks and
      promote protection factors. Therefore knowledge of resilience in patients with
      SLE is necessary. It is important that the state takes necessary actions to
      facilitate access to treatment, to educational programs and to medical support.
      Awareness and counselling sessions must be initiated to develop and promote
      individual capacities to learn how to tackle with the disease for which
      psychological support of family and doctors can play a significant role.

PMID- 24665353
TI  - Pitting type of pretibial edema in a patient with silent thyroiditis successfully
      treated by angiotensin ii receptor blockade.
AB  - PATIENT: Female, 56 FINAL DIAGNOSIS: Thyroiditis - silent Symptoms: Palpitations
      * pretibial pitting edema * short of breath * sweating MEDICATION: - Clinical
      Procedure: - Specialty: Endocrinology and Metabolic. OBJECTIVE: Unknown etiology.
      BACKGROUND: Hyper- or hypothyroidism sometimes causes pretibial myxedema
      characterized by non-pitting infiltration of a proteinaceous ground substance.
      However, in those patients, the "pitting" type of pretibial edema as a result of
      increased sodium and fluid retention or vascular hyper-permeability rarely
      occurs, except in cases complicated by heart failures due to severe
      cardiomyopathy or pulmonary hypertension. CASE REPORT: A 56-year-old woman
      developed bilateral pretibial pitting edema, followed by occasional sweating,
      palpitations, and shortness of breath, which persisted for more than 2 months.
      The diagnosis of hyperthyroidism due to silent thyroiditis was supported by
      elevated levels of free thyroxine (T4) and triiodothyronine (T3), with a marked
      decrease in thyroid-stimulating hormone (TSH), and the negative results for TSH
      receptor antibodies with typical findings of destructive thyrotoxicosis. Despite
      her "pitting" type of pretibial edema, a chest radio-graph demonstrated the
      absence of cardiomyopathy or congestive heart failure. Oral administration of
      angiotensin II receptor blocker (ARB) was initiated for her systolic
      hypertension, with a relatively higher elevation of plasma renin activity
      compared to that of the aldosterone level. Although the symptoms characteristic
      to hyperthyroidism, such as increased sweating, palpitations and shortness of
      breath, slowly improved with a spontaneous resolution of the disease, ARB quickly
      resolved the pretibial pitting edema shortly after the administration..
      CONCLUSIONS: In this case, increased activity of the renin-angiotensin
      aldosterone system stimulated by thyroid hormone was likely responsible for the
      patient's pitting type of edema. The pharmacological blockade of the renin
      angiotensin-aldosterone system was thought to be effective for the quick
      resolution of the symptom.

PMID- 24665354
TI  - Primary culture of trigeminal satellite glial cells: a cell-based platform to
      study morphology and function of peripheral glia.
AB  - Primary cell culture provides an experimental platform in which morphology,
      physiology, and cell-cell communication pathways can be studied under a well
      controlled environment. Primary cell cultures of peripheral and central glia
      offer unique possibilities to clarify responses and pathways to different
      stimuli. Peripheral glia, satellite glial cells (SGCs), which surround neuronal
      cell bodies within sensory ganglia, have recently been known as key players in
      inflammation and neuronal sensitization. The objectives of this study were 1) to
      establish a cell-based platform of cultured trigeminal SGCs to study glial marker
      expression and functions under control conditions; 2) to validate the cell-based
      platform by prostaglandin E2 (PGE2) release response following administration of
      Cisplatin; and 3) to investigate inhibition of PGE2 release by glial modulators,
      Ibudilast and SKF86002. Primary cell cultures of SGCs from rat trigeminal ganglia
      were established following enzymatically and mechanically dissociation of the
      ganglia. Cultures were characterized in vitro for up to 21 days post isolation
      for morphological and immunocytochemical characteristics. PGE2 release,
      determined by ELISA, was used as a pro-inflammatory marker to characterize SGCs
      response to chemotherapeutic agent, Cisplatin, known to contribute in
      chemotherapy-induced peripheral neuropathy. Our results indicate that 1) isolated
      SGCs maintained their characteristics in vitro for up to 21 days; 2) Cisplatin
      enhanced PGE2 release from the SGCs, which was attenuated by Ibudilast and
      SKF86002. These findings confirm the utility and validity of the cultured
      trigeminal SGCs platform for glial activation and modulation; and suggest further
      investigation on Ibudilast and SKF86002 in prevention of chemotherapy-induced
      pain. 

PMID- 24665355
TI  - Parametric transfer function analysis and modeling of blood flow autoregulation
      in the optic nerve head.
AB  - The aim of the study was to establish a parametric transfer function to describe
      the relationship between ocular perfusion pressure (OPP) and blood flow (BF) in
      the optic nerve head (ONH). A third-order parametric theoretical model was
      proposed to describe the ONH OPP-BF relationship within the lower OPP range of
      the autoregulation curve (< 80 mmHg) based on experimentally induced BF response
      to a rapid intraocular pressure (IOP) increase in 6 rhesus monkeys. The
      theoretical and actual data fitted well and suggest that this parametric third
      order transfer function can effectively describe both the linear and nonlinear
      feature in dynamic and static autoregulation in the ONH within the OPP range
      studied. It shows that the BF autoregulation fully functions when the OPP was >
      40 mmHg and becomes incomplete when the OPP was < 40 mmHg. This model may be used
      to help investigating the features of autoregulation in the ONH under different
      experimental conditions. 

PMID- 24665356
TI  - Evening primrose oil ameliorates platelet aggregation and improves cardiac
      recovery in myocardial-infarct hypercholesterolemic rats.
AB  - Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their role in
      cardiovascular disease (CVD). We proposed that Evening prime rose oil (EPO) can
      improve the outcome of a heart with myocardial infarction (MI) in the presence of
      diet-induced hyperaggregability. This study was designed to examine its
      cholesterol lowering, antithrombotic and anti-inflammatory effects. High fat diet
      was administered for 4 weeks then MI was induced by isoproterenol (85
      mg/kg/s.c./24 h). Treatment with EPO (5 or 10 gm/kg/day) for 6 weeks improved the
      electrocardiographic pattern, serum lipid profile, cardiac biomarkers as well as
      Platelet aggregation percent. We reported decreased serum level of TNF-alpha, IL
      6 and COX-2 with attenuation of TNF-alpha and TGF-beta in the cardiac homogenate.
      Moreover, histopathology revealed marked amelioration. Finally, we provide
      evidence that EPO improve cardiac recovery in hypercholesterolemic myocardial
      infarct rats. These effects are attributed to direct hypocholesterolemic effect
      and indirect effect on the synthesis of eicosanoids (prostaglandins, cytokines). 

PMID- 24665357
TI  - NOS1AP modulates intracellular Ca(2+) in cardiac myocytes and is up-regulated in
      dystrophic cardiomyopathy.
AB  - NOS1AP gene (nitric oxide synthase 1-adaptor protein) is strongly associated with
      abnormalities in the QT interval of the electrocardiogram and with sudden cardiac
      death. To determine the role of NOS1AP in the physiology of the cardiac myocyte,
      we assessed the impact of silencing NOS1AP, using siRNA, on [Ca(2+)]i transients
      in neonatal cardiomyocytes. In addition, we examined the co-localization of
      NOS1AP with cardiac ion channels, and finally, evaluated the expression of NOS1AP
      in a mouse model of dystrophic cardiomyopathy. Using siRNA, NOS1AP levels were
      reduced to ~30% of the control levels (p<0.05). NOS1AP silencing in cardiac
      myocytes reduced significantly the amplitude of electrically evoked calcium
      transients (p<0.05) and the degree of S-nitrosylation of the cells (p<0.05).
      Using confocal microscopy, we evaluated NOS1AP subcellular location and
      interactions with other proteins by co-localization analysis. NOS1AP showed a
      high degree of co-localization with the L-type calcium channel and the inwardly
      rectifying potassium channel Kir3.1, a low degree of co-localization with the
      ryanodine receptor (RyR2) and alfa-sarcomeric actin and no co-localization with
      connexin 43, suggesting functionally relevant interactions with the ion channels
      that regulate the action potential duration. Finally, using immunofluorescence
      and Western blotting, we observed that in mice with dystrophic cardiomyopathy,
      NOS1AP was significantly up-regulated (p<0.05). These results suggest for a role
      of NOS1AP on cardiac arrhythmias, acting on the L-type calcium channel, and
      potassium channels, probably through S-nitrosylation. 

PMID- 24665358
TI  - Comparison between cafeteria and high-fat diets in the induction of metabolic
      dysfunction in mice.
AB  - This study sought to compare the metabolic responses induced by high-fat (HF)
      diet and cafeteria (CA) diet in mice. Adult male C57BL/6J mice were assigned into
      groups fed a chow (C, n=13), CA (n=12) or HF (n=11) diet during 12 weeks. Diets
      did not change body weight, Lee index, inguinal subcutaneous fat, the weight of
      organs and muscles, resting arterial pressure and heart rate. CA and HF increased
      visceral fat pad mass compared to C group, but only CA group showed greater
      adipocyte diameter and food intake compared to the C. Food intake was reduced in
      HF compared to C group. CA and HF showed hyperglycemia in the 3(rd), 6(th), 9(th)
      and 12(th) week and all values were higher in CA than HF, except in the 6(th)
      week. CA group showed glucose intolerance (GI) in the 6(th) week, while HF group
      did not show GI until the 9(th) week. CA decreased insulin sensitivity compared
      to C in the 12(th) week (kITT=3.3+/-0.2%/min vs. 4.2+/-0.1%/min). CA and HF
      groups presented higher insulin, leptin, total cholesterol, LDL-C, triglycerides
      and FFA levels compared to the C group. Total cholesterol and LDL-C in mg/dL were
      higher in the HF (161.9+/-7.2 and 57.5+/-13.4) than the CA (110.5+/-9.1 and
      48.5+/-11.4), and HDL-C was higher in the HF than in the C and CA groups. In
      conclusion, the CA diet was more efficient to induce hyperphagia, adipocyte
      hypertrophy, hyperglycemia, earlier GI and insulin resistance, while the HF diet
      was more efficient to induce lipid profile changes. 

PMID- 24665359
TI  - Effect of Tai Chi exercise on the physical and mental health of the elder
      patients suffered from anxiety disorder.
AB  - OBJECTIVE: Observe the effect of Tai Chi exercise on the rehabilitation of elder
      patients suffered from the anxiety disorder. METHODS: 32 elder patients suffered
      from the anxiety disorder are randomly divided into the experimental group and
      the control group and each of them consists of 16 patients. The control group
      only receives the drug therapy, while the experimental group is treated with Tai
      Chi exercise in addition to the drug therapy. When they are chosen and 45 days
      after treatment, they are respectively evaluated by Hamilton Anxiety Scale (HAMA)
      and Generic Quality of Life Inventory-74 (GQOLI-74). The cured patients stop the
      drug therapy, but the cured patients in the experimental group continue to do Tai
      Chi exercise after stopping the drug therapy. After tracing and investigating
      each cured patient for 2 months, test and evaluate whether their disease reoccurs
      within the 2 months. RESULTS: After 45 days' treatment, it is found that HAMA and
      GQOLI-74 scores of the patients in the experimental group are improved
      significantly in comparison with those in the time of their selection and those
      in the control group (P<0.05); upon tracing and investigation of the cured
      patients, it is found that the recurrence rate is 42.86% in the control group,
      while that of the experimental group is only 9.09%. CONCLUSION: After the elder
      patients suffered from the anxiety disorder are treated with Tai Chi exercise in
      addition to the drug therapy, their effect is more significant than those who
      only are treated by the drug. Meanwhile, if the patients are only treated by the
      drug, their disease is easy to reoccur after curing. However, if they insist on
      Tai Chi exercise, the recurrence rate is low and the effect is significant.

PMID- 24665360
TI  - Effect of air temperature on the rectal temperature gradient at rest and during
      exercise.
AB  - The purpose of the current study was to determine the effect of air temperature
      on the rectal temperature gradient at rest and during exercise. It was
      hypothesized that the rectal temperature gradient would be exacerbated in cold
      environments and attenuated in warm environments both at rest and during
      exercise. Each subject completed three exercise bouts on a motor driven treadmill
      at approximately 55% of their previously determined maximal oxygen uptake. Three
      different air temperatures (10, 22, 39 degrees C) were used for the exercise
      bouts. Rectal temperature was measured at rest and every 5 min during each
      exercise bout using 4 temperature sensors affixed at 4, 7, 10 and 13 cm past the
      anal sphincter. Readings obtained from the 4-cm depth were significantly (p<0.05)
      lower than those obtained at deeper insertion depths both at rest and during
      exercise for all three air temperatures. Furthermore, the results showed that the
      rectal temperature gradient was exacerbated in cold environments and attenuated
      in warm environments both at rest and during exercise. 

PMID- 24665361
TI  - The endocytosis gene END3 is essential for the glucose-induced rapid decline of
      small vesicles in the extracellular fraction in Saccharomyces cerevisiae.
AB  - BACKGROUND: Protein secretion is a fundamental process in all living cells.
      Gluconeogenic enzymes are secreted when Saccharomyces cerevisiae are grown in
      media containing low glucose. However, when cells are transferred to media
      containing high glucose, they are internalized. We investigated whether or not
      gluconeogenic enzymes were associated with extracellular vesicles in glucose
      starved cells. We also examined the role that the endocytosis gene END3 plays in
      the internalization of extracellular proteins/vesicles in response to glucose
      addition. METHODS: Transmission electron microscopy was performed to determine
      the presence of extracellular vesicles in glucose-starved wild-type cells and the
      dynamics of vesicle transport in cells lacking the END3 gene. Proteomics was used
      to identify extracellular proteins that associated with these vesicles. RESULTS:
      Total extracts prepared from glucose-starved cells consisted of about 95% small
      vesicles (30-50 nm) and 5% large structures (100-300 nm). The addition of glucose
      caused a rapid decline in small extracellular vesicles in wild-type cells.
      However, most of the extracellular vesicles were still observed in cells lacking
      the END3 gene following glucose replenishment. Proteomics was used to identify 72
      extracellular proteins that may be associated with these vesicles. Gluconeogenic
      enzymes fructose-1,6-bisphosphatase, malate dehydrogenase, isocitrate lyase, and
      phosphoenolpyruvate carboxykinase, as well as non-gluconeogenic enzymes
      glyceraldehyde-3-phosphate dehydrogenase and cyclophilin A, were distributed in
      the vesicle-enriched fraction in total extracts prepared from cells grown in low
      glucose. Distribution of these proteins in the vesicle-enriched fraction required
      the integrity of the membranes. When glucose was added to glucose-starved wild
      type cells, levels of extracellular fructose-1,6-bisphosphatase, malate
      dehydrogenase, isocitrate lyase, phosphoenolpyruvate carboxykinase,
      glyceraldehyde-3-phosphate dehydrogenase, and cyclophilin A were reduced. In
      contrast, in cells lacking the END3 gene, levels of these proteins in the
      extracellular fraction remained high. CONCLUSION: The END3 gene is required for
      the rapid decline of extracellular proteins and vesicles in response to glucose
      addition.

PMID- 24665362
TI  - Regeneration of reptilian scales after wounding: neogenesis, regional difference,
      and molecular modules.
AB  - Lizard skin can produce scales during embryonic development, tail regeneration,
      and wound healing; however, underlying molecular signaling and extracellular
      matrix protein expression remains unknown. We mapped cell proliferation,
      signaling and extracellular matrix proteins in regenerating and developing lizard
      scales in different body regions with different wound severity. Following lizard
      tail autotomy (self-amputation), de novo scales regenerate from regenerating tail
      blastema. Despite topological differences between embryonic and adult scale
      formation, asymmetric cell proliferation produces the newly formed outer scale
      surface. Regionally different responses to wounding were observed; open wounds
      induced better scale regeneration from tail skin than trunk skin. Molecular
      studies suggest NCAM enriched dermal regions exhibit higher cell proliferation
      associated with scale growth. beta-catenin may be involved in epidermal scale
      differentiation. Dynamic tenascin-C expression suggests its involvement in
      regeneration. We conclude that different skin regions exhibit different
      competence for de novo scale formation. While cellular and morphogenetic paths
      differ during development and regeneration of lizard scale formation, they share
      general proliferation patterns, epithelial-mesenchymal interactions and similar
      molecular modules composed of adhesion and extracellular matrix molecules.

PMID- 24665363
TI  - Adolescence, Stress and Cortisol in Autism Spectrum Disorders.
AB  - Adolescence, the transition between childhood and adulthood, is a period of
      remarkable physiological, psychological and social change. A variety of
      physiological changes coincide with the dynamic transition, which is evident in
      the regulation and responsivity of the Limbic-Hypothalamic-Pituitary
      Adrenocortical (LHPA) axis. Specifically, elevations in diurnal basal cortisol
      levels have been reported, as well as higher cortisol in response to perceived
      stressors. While this enhanced responsivity may help prepare the individual to
      adapt to increased demands and new challenges, it may also mark a time of
      increased vulnerability in populations already prone to enhanced physiological
      arousal and poor adaption to change, such as autism. To date most studies
      investigating the integrity of the LHPA axis in children with autism spectrum
      disorders (ASD) have shown more variable diurnal regulation and a pattern of
      enhanced responsivity to stress. There is also evidence of more marked reactivity
      over development suggesting that adolescence may be a time of increased risk for
      enhanced physiological arousal and social stress. The following review briefly
      summarizes the literature to date on autism, adolescence and salivary cortisol.
      The current summary suggests that enhanced study of the interplay between social
      functioning and stress during the adolescent period in ASD is warranted.

PMID- 24665364
TI  - A metabolomic perspective on coeliac disease.
AB  - Metabolomics is an "omic" science that is now emerging with the purpose of
      elaborating a comprehensive analysis of the metabolome, which is the complete set
      of metabolites (i.e., small molecules intermediates) in an organism, tissue,
      cell, or biofluid. In the past decade, metabolomics has already proved to be
      useful for the characterization of several pathological conditions and offers
      promises as a clinical tool. A metabolomics investigation of coeliac disease (CD)
      revealed that a metabolic fingerprint for CD can be defined, which accounts for
      three different but complementary components: malabsorption, energy metabolism,
      and alterations in gut microflora and/or intestinal permeability. In this review,
      we will discuss the major advancements in metabolomics of CD, in particular with
      respect to the role of gut microbiome and energy metabolism. 

PMID- 24665365
TI  - Retrospective observations on the ability to diagnose and manage patients with
      asthma through the use of impulse oscillometry: comparison with spirometry and
      overview of the literature.
AB  - OBJECTIVE: Impulse oscillometry (IOS) is an evolving technology for the diagnosis
      and followup of patients with asthma. Our objective is to review the findings on
      patients who underwent both spirometry and IOS during clinical evaluations of
      their asthma. The goal was to retrospectively evaluate IOS during the initial
      diagnosis and followup of patients with asthma in comparison with spirometry.
      METHODS: We routinely perform IOS and spirometry evaluation in patients with
      suspected asthma during baseline visits and at followup. We reviewed the data on
      39 patients over the age of 13 with asthma at baseline and following treatment
      with inhaled corticosteroids. IOS and spirometry were both done at baseline,
      following short acting bronchodilator administration, and at followup after at
      least three months of inhaled corticosteroid treatment. RESULTS: IOS showed
      improvement in airway function both initially, following short acting
      bronchodilator introduction, and later after initiation of long term inhaled
      corticosteroid treatment, even when the spirometry did not reveal improvement. We
      noted the IOS improvement in the reactance or AX as well as the resistance in
      smaller airways or R5. CONCLUSION: IOS may provide a useful measure towards
      identifying an asthma diagnosis and followup without inducing the extra
      respiratory effort spirometry requires.

PMID- 24665366
TI  - Periventricular lesions help differentiate neuromyelitis optica spectrum
      disorders from multiple sclerosis.
AB  - Objective. To compare periventricular lesions in multiple sclerosis (MS) and
      neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal
      and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and
      40 group frequency-matched MS patients were evaluated by two neuroradiologists.
      On axial FLAIR, periventricular area was characterized as free of lesions/smooth
      bordered ("type A") or jagged-bordered ("type B") pattern. On sagittal FLAIR, the
      images were evaluated for presence of "Dawson's fingers." Results. Type A pattern
      was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in
      5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader
      1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers
      were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS,
      Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2.
      The differences in periventricular patterns and Dawson's finger detection between
      NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers
      and "jagged-bordered" periventricular hyperintensities are typical of MS and
      almost never seen in NMOsd, which suggests a practical method for differentiating
      the two diseases. 

PMID- 24665367
TI  - Association of body mass index with hemoglobin concentration and iron parameters
      in Iranian population.
AB  - Background. Studies have reported that obesity has an adverse effect on iron
      metabolism. Obesity is characterized by chronic, low-grade, systemic inflammation
      and anemia of chronic disease with elevated serum ferritin and decreased level of
      serum iron, transferrin saturation, and hemoglobin. Therefore, we examined the
      association of body mass index with hemoglobin concentration and iron parameters
      in this study. Methods. This cross-sectional study was conducted in Yazd to
      assess the relation of body mass index with hemoglobin and iron parameters among
      406 adult patients 18-65 years old. Diabetes and conditions that could influence
      body iron stores were excluded. Results. There is no difference in hemoglobin
      concentrations, MCV, serum iron, TIBC, transferrin saturation index, and ferritin
      between normal weight, overweight, and obese persons. Conclusion. Nutritional
      status of persons and intake of high iron foods by obese persons should be
      considered. Also, other inflammatory markers should be evaluated in the future
      studies. 

PMID- 24665368
TI  - Evaluation of the Efficacy of Topical Tetracycline in Enhancing the Effect of
      Narrow Band UVB against Vitiligo: A Double-Blind, Randomized, Placebo-Controlled
      Clinical Trial.
AB  - Background. Vitiligo is a pigmentary disorder characterized by depigmented
      macules due to absence of melanocytes. Increased levels of tumor necrosis factor
      alpha and interleukin-1 in the epidermis of lesions may play a role in
      keratinocyte apoptosis and less production of melanogenic cytokines.
      Tetracyclines reduce production of tumor necrosis factor alpha and interleukin-1.
      Objective. To evaluate the effect of topical tetracycline on vitiligo patients on
      phototherapy. Methods. Thirty cases of generalized stable vitiligo were chosen
      randomly and pigmentation of two assigned lesions on right and left sides (same
      size and location) was determined by vitiligo area severity index, and medication
      and placebo were randomly assigned to be applied twice daily on either right or
      left side, respectively. Images were taken of the lesions at the end of the 4th,
      8th, and 12th weeks and pigmentations were compared to baseline using
      aforementioned index. The patients also took narrow band ultraviolet B two to
      three times a week. Results. Mean pigmentation, based on vitiligo area severity
      index, changed significantly from 90.1667 to 86.6667 (P = 0.026) and on placebo
      side from 89.6667 to 86.8333 (P = 0.026). There was no significant difference
      between medication and placebo sides in terms of pigmentation (P = 0.566).
      Conclusions. No significant difference in improving repigmentation between
      medication and placebo sides was seen. 

PMID- 24665369
TI  - Serum Levels of the Adipokine Zinc- alpha 2-glycoprotein Are Decreased in
      Patients with Hypertension.
AB  - Objective. Zinc-alpha2-glycoprotein (ZAG) has recently been proposed as a new
      adipokine involved in body weight regulation. The purpose of this study is to
      investigate serum levels of ZAG in patients with hypertension and its association
      with related characteristics. Methods. 32 hypertension patients and 42 normal
      controls were recruited and the relationship between serum ZAG, total and high
      molecular weight (HMW) adiponectin, and tumor necrosis factor-alpha (TNFalpha)
      determined by enzyme-linked immunosorbent assay (ELISA) and metabolic-related
      parameters was investigated. Results. Serum ZAG concentrations were significantly
      lowered in patients with hypertension compared with healthy controls (61.4 +/- 32
      versus 78.3 +/- 42 MUg/mL, P < 0.05). The further statistical analysis
      demonstrated that serum ZAG levels were negatively correlated with waist-to-hip
      ratio (WHR) (r = -0.241, P < 0.05) and alanine aminotransferase (ALT) (r = 
      0.243, P < 0.05). Additionally, serum HMW adiponectin significantly decreased,
      while TNFalpha greatly increased in hypertension patients as compared with
      healthy controls (2.32 +/- 0.41 versus 5.24 +/- 1.02 MUg/mL, 3.30 +/- 1.56 versus
      2.34 +/- 0.99 pg/mL, P < 0.05). Conclusions. Serum ZAG levels are significantly
      lowered in hypertension patients and negatively correlated with obesity-related
      item WHR, suggesting ZAG is a factor associated with hypertension. 

PMID- 24665370
TI  - Packages of participation: Swedish employees' experience of Lean depends on how
      they are involved.
AB  - BACKGROUND: Lean Production is a dominant approach in Swedish and global
      manufacturing and service industries. Studies of Lean's employee effects are few
      and contradictory. PURPOSE: Employee effects from Lean are likely not uniform.
      This paper investigates the effect of employees' participation on their
      experiences of Lean. METHOD: This study investigated how different packages of
      employee participation in Lean affected manufacturing workers' experiences of
      Lean. During 2008-2011, qualitative and quantitative data were collected from
      Swedish manufacturing companies participating in the national Swedish Lean
      Production program Produktionslyftet. Data from 129 surveys (28 companies), 39
      semi-structured interviews, and 30 reports were analyzed. In the main analysis,
      comparisons were made of the survey-reported Lean experiences of employees in
      three groups: temporary group employees (N = 36), who participated in Lean mostly
      through intermittent projects; continuous group employees (N = 69), who
      participated through standing improvement groups; and combined group employees (N
      = 24), who participated in both ways. RESULTS: Continuous group employees had the
      most positive experience of Lean, followed by the combined group. Temporary group
      employees had the least positive experiences, being less likely than their
      counterparts to report that Lean improved teamwork, occupational safety, and
      change-related learning, decision making, and authority. CONCLUSIONS: These
      findings support the importance of continuous, structured opportunities for
      participation but raise the possibility that more participation may result in
      greater workload and role overload, mitigating some benefits of employee
      involvement. Consequently, companies should consider involving employees in
      change efforts but should attend to the specific design of participation
      activities.

PMID- 24665371
TI  - A bacterial encoded protein induces extreme multinucleation and cell-cell
      internalization in intestinal cells.
AB  - Despite extensive study, the molecular mechanisms that lead to multinucleation
      and cell enlargement (hypertrophy) remain poorly understood. Here, we show that a
      single bacterial virulence protein, EspF, from the human pathogen
      enteropathogenic E. coli induces extreme multi-nucleation in small intestinal
      epithelial cells. Ectopic expression of EspF induced cell-cell internalization
      events, presumably responsible for the enlarged multinucleated cells. These
      extreme phenotypes were dependent on a C-terminal polyproline-rich domain in EspF
      and not linked to the targeting of mitochondria or the nucleolus. The subversive
      functions of EspF may provide valuable insight into the molecular mechanisms that
      mediate cell fusion, multinucleation and cell hypertrophy. 

PMID- 24665372
TI  - JAM-A and aPKC: A close pair during cell-cell contact maturation and tight
      junction formation in epithelial cells.
AB  - Cell-cell adhesion plays a critical role in the formation of barrier-forming
      epithelia. The molecules which mediate cell-cell adhesion frequently act as
      signaling molecules by recruiting and/or assembling cytoplasmic protein
      complexes. Junctional Adhesion Molecule (JAM)-A interacts with the cell polarity
      protein PAR-3, a member of the PAR-3-aPKC-PAR-6 complex, which regulates the
      formation of cell-cell contacts and the development of tight junctions (TJs). In
      our recent study we found that JAM-A is localized at primordial, spot-like cell
      cell junctions (pAJs) in a non-phosphorylated form. After the recruitment of the
      PAR-aPKC complex and its activation at pAJs, aPKC phosphorylates JAM-A at Ser285
      to promote the maturation of immature junctions. In polarized epithelial cells,
      aPKC phosphorylates JAM-A selectively at the TJs to maintain the barrier function
      of TJs. Thus, through mutual regulation, JAM-A and aPKC form a functional unit
      that regulates the establishment of barrier-forming junctions in vertebrate
      epithelial cells. 

PMID- 24665373
TI  - Linking membrane trafficking and intestinal homeostasis.
AB  - A major challenge for the human body is to maintain symbiotic relationships with
      bacterial communities that colonize their intestines. Although several molecules
      important for intestinal homeostasis have been discovered, the vast array still
      needs to be identified. We approached this task using a forward genetic approach,
      which revealed several molecules essential for intestinal homeostasis. One
      recently identified molecule is Ypt1p-interacting protein 1 domain family, member
      6 (Yipf6). Mice with a null mutation in Yipf6 are hypersensitive to dextran
      sulfate sodium (DSS) induced colitis and develop spontaneous intestinal
      inflammation. Members of the Yip1 family are believed to be involved in ER to
      Golgi membrane transport.   In this review we summarize recent advances in the
      understanding of genes involved in intestinal homeostasis with a specific focus
      on the Yip family members. We speculate on how deficiency or dysfunction of Yip
      molecules may dysregulate intestinal homeostasis leading to pathogenic states. 

PMID- 24665374
TI  - Emerging roles of Semaphorins in the regulation of epithelial and endothelial
      junctions.
AB  - Tissue barriers maintain homeostasis, protect underlying tissues, are remodeled
      during organogenesis and injury and limit aberrant proliferation and
      dissemination. In this context, endothelial and epithelial intercellular
      junctions are the primary targets of various cues. This cellular adaptation
      requires plasticity and dynamics of adhesion molecules and the associated
      cytoskeleton, as well as the adhesive-linked signaling platforms. It is therefore
      not surprising that the guidance molecules from the Semaphorin family arise as
      novel modifiers of epithelia and endothelia in development and diseases. This
      review will focus on the actions of Semaphorins, and their cognate receptors,
      Plexins and Neuropilins, on epithelial and endothelial barrier properties. 

PMID- 24665376
TI  - A complex affair: Attraction and repulsion make occludin and ZO-1 function!
AB  - Tight junctions (TJs) are protein complexes comprised of claudins, which anchor
      them in the membrane and numerous cytosolic scaffolding proteins including MAGI,
      MUPP1, cingulin and members of the Zonula Occludens (ZO) family. Originally,
      their main function was thought to be as a paracellular barrier. More recently,
      however, additional roles in signal transduction, differentiation and
      proliferation have been reported. Dysregulation is associated with a wide range
      of disease states, including diabetic retinopathy, irritable bowel disease and
      some cancers. ZO proteins and occludin form a protein complex that appears to act
      as a master regulator of TJ assembly/disassembly. Recent studies have highlighted
      the structural character of the primary ZO-1:occludin interaction and identified
      regions on occludin that control association and disassociation of TJ in a
      phosphorylation-dependent manner. We hypothesize that regions within ZO-1 in the
      so-called U5 and U6 regions behave in a similar manner. 

PMID- 24665375
TI  - Role of grainyhead-like 2 in the formation of functional tight junctions.
AB  - Epithelial cells develop intercellular junctions, including tight junctions (TJs)
      and adherens junctions (AJs). In epithelial tissues, TJs act as barriers that
      protect bodies from dehydration, infection and toxic substances. However, the
      molecular mechanisms regulating the establishment of functional TJs during
      organogenesis remain largely unknown. Recently, we identified grainyhead-like 2
      (Grhl2) as a transcription factor that is specifically expressed in
      cholangiocytes, which are epithelial cells lining the bile duct tubules in the
      liver. Using our three-dimensional (3D) culture system of hepatic progenitor
      cells, we demonstrated that Grhl2 enhanced barrier functions of hepatic
      progenitor cells by upregulating claudin (Cldn) 3 and Cldn4, thereby promoting
      epithelial morphogenesis. In addition, we identified Rab25 as another target of
      Grhl2, which promotes the localization of Cldn4 at TJs. Our results indicate that
      a transcription factor promotes epithelial morphogenesis by establishing
      functional TJs by not only regulating the transcription of Cldns but also
      affecting their localization at TJs. 

PMID- 24665377
TI  - Overcoming physical barriers in cancer therapy.
AB  - Most solid tumors are of epithelial origin and, although malignant cells are de
      differentiated, they maintain intercellular junctions, a key feature of
      epithelial cells, both in the primary tumor as well as in metastatic lesions.
      These intercellular junctions represent a protective mechanism against attacks by
      the host's immune system and pose as physical barriers that prevent intratumoral
      penetration and dissemination of cancer therapeutics. A key protein of epithelial
      junctions is desmoglein 2 (DSG2). DSG2 is consistently upregulated in all cancers
      analyzed. Recently, we demonstrated that a group of human adenoviruses (Ad
      serotypes 3, 7, 11 and 14) use DSG2 as a primary attachment receptor for the
      infection of cells. We subsequently created a small recombinant protein derived
      from Ad serotype 3, which binds to DSG2 and triggers transient opening of
      epithelial intercellular junctions. We named the protein "JO-1" ("junction opener
      -1"). JO-1 is a small protein that can easily be produced in E. coli. JO-1
      binding to and clustering of DSG2 triggers an epithelial-to-mesenchymal
      transition that results in transient opening of epithelial junctions. We have
      shown in over 25 xenograft tumor models that the intravenous injection of JO-1
      increased the efficacy of monoclonal and chemotherapy, subsequently reducing the
      required treatment dose and concomitantly reducing the toxic side effect of these
      treatments. The application of JO-1 has not been associated with toxicities in
      safety studies performed in human DSG2-transgenic mice and monkeys. 

PMID- 24665378
TI  - How do your contacts (or their absence) shape your fate?
AB  - Tissue accumulation of contractile myofibroblasts is a key feature of a multitude
      of fibrotic diseases. Myofibroblast generation either from epithelial or
      mesenchymal precursors involves the activation of a myogenic program, hallmarked
      by the expression of alpha-smooth muscle actin (SMA). Recent research suggests
      that this robust phenotypic reprogramming requires two critical inputs: the
      fibrogenic cytokine transforming growth factor-beta1 (TGFbeta) and an injury (or
      absence) of intercellular junctions. This two-hit paradigm of epithelial
      myofibroblast transition (EMyT) postulates that the injured (contact-deprived)
      epithelium is locally and selectively sensitive (topically susceptible) to the
      transforming effect of TGFbeta, while the intact areas are quite resistant to the
      phenotype-changing effect of this cytokine. Searching for molecular mechanisms
      underlying the synergy between contact injury and TGFbeta, we found that an
      interplay among three multifunctional transcriptional (co)activators, the
      junction component beta-catenin, the TGFbeta receptor target Smad3, and the actin
      cytoskeleton-regulated myocardin-related transcription factor (MRTF) controls the
      magnitude and timing of SMA expression.(1) Moreover, this regulation is realized
      not only at the transcriptional level. Notably, these factors form a
      pretranscriptional circuit, in which they impact each other's activity and
      stability. Based on this recent paper we ponder about the mechanisms of cellular
      plasticity in the context of EMyT. We propose that topical susceptibility to
      TGFbeta, triggered by cell contact-modulated pretranscriptional and
      transcriptional control is realized through the crosstalk of a few master
      regulators, whose coordinated action tailors SMA expression and contributes to
      the major decision of whether injury leads to healing or fibrosis. 

PMID- 24665379
TI  - Locking endothelial junctions blocks leukocyte extravasation, but not in all
      tissues.
AB  - The passage of leukocytes across the blood vessel wall is a fundamental event in
      the inflammatory response. During the last decades, there has been significant
      progress in understanding the molecular mechanisms involved in leukocyte
      transmigration. However, it is still a matter of debate whether leukocytes
      migrate paracellularly or transcellularly through an endothelial cell layer. We
      could recently show that a VE-cadherin-alpha-catenin fusion protein locks
      endothelial junctions in the skin and strongly reduces leukocyte diapedesis in
      lung, skin and cremaster, establishing the paracellular route as the major
      transmigration pathway in these tissues. However, the homing of naive lymphocytes
      into lymph nodes and extravasation of neutrophils in the inflamed peritoneum were
      not affected by VE-cadherin-alpha-catenin. This unexpected heterogeneity of the
      diapedesis process in different tissues as well as the complexity and dynamics of
      the cadherin-catenin complex in regulating endothelial junctions will be
      discussed. 

PMID- 24665380
TI  - Possible roles of LI-Cadherin in the formation and maintenance of the intestinal
      epithelial barrier.
AB  - LI-cadherin belongs to the so called 7D-cadherins, exceptional members of the
      cadherin superfamily which are characterized by seven extracellular cadherin
      repeats and a small cytosolic domain. Under physiological conditions LI-cadherin
      is expressed in the intestine and colon in human and mouse and in the rat also in
      hepatocytes. LI-cadherin was shown to act as a functional Ca(2+)-dependent
      adhesion molecule, linking neighboring cells and a lot of biophysical and
      biochemical parameters were determined in the last time. It is also known that
      dysregulated LI-cadherin expression can be found in a variety of diseases.
      Although there are several hypothesis and theoretical models concerning the
      function of LI-cadherin, the physiological role of LI-cadherin is still
      enigmatic. 

PMID- 24665381
TI  - Cortactin regulates the activity of small GTPases and ICAM-1 clustering in
      endothelium: Implications for the formation of docking structures.
AB  - Cortactin is an actin-binding molecule that regulates various cellular processes
      requiring actin dynamics. We recently described cortactin-deficient mice and
      despite its pivotal role for actin remodeling in vitro, these mice are
      surprisingly healthy. Analyzing cortactin functions in endothelium under
      inflammatory conditions, we found that cortactin is required for endothelial
      barrier functions and leukocyte extravasation in vivo. Importantly, these effects
      were not regulated by defective actin dynamics but instead by a failure to
      activate the small GTPases Rap1 and RhoG in endothelial cells. Defective RhoG
      signaling led to reduced ICAM-1 clustering that supported the interaction with
      leukocytes. These clusters originally seen as rings surrounding adherent
      leukocytes actually represented in many cases ICAM-1 containing protrusions as
      they were described before as docking structures. Thus, cortactin is essential
      for the formation of endothelial docking structures as well as for leukocyte
      adhesion and extravasation. 

PMID- 24665382
TI  - S-nitrosation of proteins: An emergent regulatory mechanism in microvascular
      permeability and vascular function.
AB  - Nitric oxide (NO) is a key factor in inflammation as it regulates microvascular
      permeability, leukocyte adhesion and wound healing. This mini-review addresses
      mainly spatial and temporal requirements of NO regulatory mechanisms, with
      special emphasis on S-nitrosation. Endothelial nitric oxide synthase (eNOS)
      derived NO induces S-nitrosation of p120 and beta-catenin, particularly in
      response to platelet-activating factor (PAF), and through traffic and
      interactions at the adherens junction promotes endothelial hyperpermeability. S
      nitrosation is a determinant in vascular processes such as vasodilation and
      leukocyte-endothelium interactions. Interestingly, NO decreases leukocytes
      adhesion to endothelium, but the mechanisms are unknown. Advances in NO molecular
      biology and regulation may serve as a basis for the development of new
      therapeutic strategies in the treatment of diseases characterized by inflammation
      such as ischemia-reperfusion injury, stroke, cancer and atherosclerosis. 

PMID- 24665383
TI  - Welcome to tissue barriers.

PMID- 24665384
TI  - Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier
      function.
AB  - Blood testis barrier (BTB) is one of the tightest blood-barriers controlling the
      entry of substances into the intratubular fluid. Diabetes Mellitus (DM) is an
      epidemic metabolic disease concurrent with falling fertility rates, which
      provokes severe detrimental BTB alterations. It induces testicular alterations,
      disrupting the metabolic cooperation between the cellular constituents of BTB,
      with dramatic consequences on sperm quality and fertility. As Sertoli cells are
      involved in the regulation of spermatogenesis, providing nutritional support for
      germ cells, any metabolic alteration in these cells derived from DM may be
      responsible for spermatogenesis disruption, playing a crucial role in
      fertility/subfertility associated with this pathology. These cells have a glucose
      sensing machinery that reacts to hormonal fluctuations and several mechanisms to
      counteract hyper/hypoglycemic events. The role of DM on Sertoli/BTB glucose
      metabolism dynamics and the metabolic molecular mechanisms through which DM and
      insulin deregulation alter its functioning, affecting male reproductive potential
      will be discussed. 

PMID- 24665385
TI  - Disruption of blood-brain barrier in Alzheimer disease pathogenesis.
AB  - Blood-brain barrier (BBB) regulates transport of various molecules and maintains
      brain homeostasis. Perturbed intracellular Ca(2+) homeostasis and BBB damage have
      been implicated in the pathogenesis of Alzheimer disease (AD). Although receptor
      for advanced glycation end products (RAGE) is known to mediate Abeta transcytosis
      across the BBB, molecular mechanisms underlying Abeta-RAGE interaction-induced
      BBB alterations are largely unknown. We found enhanced permeability, decreased
      zonula occludin-1 (ZO-1) expression and increased intracellular calcium and MMP
      secretion in endothelial cells exposed to Abeta1-42. Abeta-induced changes in ZO
      1 were attenuated by neutralizing antibodies against RAGE and inhibitors of
      calcineurin (CaN) and MMPs, suggesting that Abeta-RAGE interactions disrupt tight
      junction proteins via the Ca(2+)-CaN pathway. We also found disrupted
      microvessels near Abeta plaque-deposited areas, elevated RAGE expression and
      enhanced MMP secretion in microvessels of the brains of 5XFAD mice, an animal
      model of AD. These results identify a potential molecular pathway underlying
      Abeta-RAGE interaction-induced breakage of BBB integrity. 

PMID- 24665387
TI  - ARHGEF11, a regulator of junction-associated actomyosin in epithelial cells.
AB  - Epithelial cells form organized sheets to protect underlying tissues and maintain
      the physiological environment by the assembly of tight junctions (TJs) and
      adherens junctions (AJs), which mainly regulate paracellular molecular passage
      and selective cell-cell adhesion, respectively. At the cytoplasmic surface, TJs
      and AJs associate with a specific actomyosin cytoskeletal structure called the
      perijunctional actomyosin ring (PJAR), which encircles cells in a belt-like
      manner. ZO family proteins play important roles in regulating TJ and PJAR
      organization. We recently found that ARHGEF11, a member of the RGS-RhoGEF family
      of proteins, associates with TJs by binding to ZO-1. ARHGEF11 mediates ZO-1
      dependent junction assembly and barrier formation in mammary epithelial cells.
      Another recent study demonstrated that ARHGEF11-dependent apical actomyosin
      contraction is coupled to planar cell polarity signaling in neuroepithelial cells
      for the control of neural tube formation. These findings suggest that ARHGEF11
      generally regulates apical junctions and junction-associated actomyosin in
      various epithelial tissues. 

PMID- 24665386
TI  - Mechanotransduction at the basis of endothelial barrier function.
AB  - Destabilization of cell-cell contacts involved in the maintenance of endothelial
      barrier function can lead to increased endothelial permeability. This increase in
      endothelial permeability results in an anarchical movement of fluid, solutes and
      cells outside the vasculature and into the surrounding tissues, thereby
      contributing to various diseases such as stroke or pulmonary edema. Thus, a
      better understanding of the molecular mechanisms regulating endothelial cell
      junction integrity is required for developing new therapies for these diseases.
      In this review, we describe the mechanotransduction mechanism at the basis of
      adherens junction strengthening at endothelial cell-cell contacts. More
      particularly, we report on the emerging role of alpha-catenin and EPLIN that act
      as a mechanotransmitter of myosin-IIgenerated traction forces. The interplay
      between alpha-catenin, EPLIN and the myosin-II machinery initiates the junctional
      recruitment of vinculin and alpha-actinin leading to a drastic remodeling of the
      actin cytoskeleton and to cortical actin ring reshaping. The pathways initiated
      by tyrosine phosphorylation of VE-cadherin at the basis of endothelial cell-cell
      junction remodeling is also reported, as it may be interrelated to alpha-catenin/
      EPLIN-mediated mechanotransduction mechanisms. We also describe the junctional
      mechanosensory complex composed of PECAM-1, VE-cadherin and VEGFR2 that is able
      to transmit signaling pathway under the onset of shear stress. This
      mechanosensing mechanism, involved in the earliest events promoting
      atherogenesis, is required for endothelial cell alignment along flow direction. 

PMID- 24665388
TI  - Focal adhesion kinase and actin regulatory/binding proteins that modulate F-actin
      organization at the tissue barrier: Lesson from the testis.
AB  - Focal adhesion kinase (FAK), as its name implied, is an important mediator of
      integrin-based signaling function in mammalian cells at the focal adhesion
      complex (FAC, also known as focal contact) at the cell-extracellular matrix
      interface. FAK is intimately related to cell movement, such as in macrophages,
      fibroblasts and also tumor cells. In the testis, however, FAK and two of its
      phosphorylated forms, p-FAK-Tyr(407) and -Tyr(397), are not found at the FAC
      since there is no ultrastructure analogous or similar to FAC in the mammalian
      testis vs. other epithelia. Instead, FAK and its two phosphorylated forms are
      detected along the seminiferous epithelium in the rat testis at the cell-cell
      interface in a testis-specific adherens junction (AJ) known as the ectoplasmic
      specialization (ES). ES is an F-actin-rich ultrastructure in which bundles of
      actin filaments are sandwiched in-between plasma membrane and cisternae of
      endoplasmic reticulum not found in other mammalian epithelial/endothelial cells.
      The ES is restricted to the interface of Sertoli cells and spermatids (step 8-19)
      known as the apical ES, and to the Sertoli cell-cell interface known as the basal
      ES. Interestingly, the basal ES is also an integrated component of the blood
      testis barrier (BTB), coexisting with tight junction (TJ) and gap junction (GJ),
      and it is conceivable that actin filament bundles at the ES undergo extensive
      organization, converting from their "bundled" to "de-bundled/branching"
      configuration to facilitate transport of germ cells across the epithelium and at
      the BTB during the epithelial cycle. A recent report (Lie et al. PNAS 109:12562
      12567, 2012) has demonstrated that the stage-specific and spatiotemporal
      expression of p-FAK-Tyr(407) and -Tyr(397) are crucial to the regulation of these
      events via their stage-specific and spatiotemporal expression during the
      epithelial cycle mediated by their effects on the organization of the actin
      filament bundles at the ES, involving actin binding/regulatory proteins. In this
      Commentary, we will critically evaluate these findings in light of other recent
      reports in the field. While these ideas are based on studies in the BTB in the
      rat testis, this information should be applicable and helpful to investigators
      studying other tissue barriers. 

PMID- 24665389
TI  - Ex vivo effect of gold nanoparticles on porcine synovial membrane.
AB  - Gold nanoparticles (AuNPs) have great potential as carriers for local drug
      delivery and as a primary therapeutic for treatment of inflammation. Here we
      report on the AuNP-synovium interaction in an ex vivo model of intra-articular
      application for treatment of joint inflammation. Sheets of porcine femoropatellar
      synovium were obtained post mortem and each side of the tissue samples was
      maintained in a separate fluid environment. Permeability to AuNPs of different
      sizes (5-52 nm) and biomarker levels of inflammation were determined to
      characterize the ex vivo particle interaction with the synovium.
      Lipopolysaccharide or recombinant human interleukin-1beta were added to fluid
      environments to assess the ex vivo effect of pro-inflammatory factors on
      permeability and biomarker levels. The synovium showed size selective
      permeability with only 5 nm AuNPs effectively permeating the entire tissues'
      width. This process was further governed by particle stability in the fluid
      environment. AuNPs reduced matrix metalloproteinase and lactate dehydrogenase
      activity and hyaluronic acid concentrations but had no effect on prostaglandin E2
      levels. Exposure to pro-inflammatory factors did not significantly affect AuNP
      permeation or biomarker levels in this model. Results with ex vivo tissue
      modeling of porcine synovium support an anti-inflammatory effect of AuNPs
      warranting further investigation. 

PMID- 24665390
TI  - Interleukin-4 and interleukin-13 cause barrier dysfunction in human airway
      epithelial cells.
AB  - Emerging evidence indicates that airway epithelial barrier function is
      compromised in asthma, a disease characterized by Th2-skewed immune response
      against inhaled allergens, but the mechanisms involved are not well understood.
      The purpose of this study was to investigate the effects of Th2-type cytokines on
      airway epithelial barrier function. 16HBE14o- human bronchial epithelial cells
      monolayers were grown on collagen coated Transwell inserts. The basolateral or
      apical surfaces of airway epithelia were exposed to human interleukin-4 (IL-4),
      IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP) alone or in combination
      at various concentrations and time points. We analyzed epithelial apical
      junctional complex (AJC) function by measuring transepithelial electrical
      resistance (TEER) and permeability to FITC-conjugated dextran over time. We
      analyzed AJC structure using immunofluorescence with antibodies directed against
      key junctional components including occludin, ZO-1, beta-catenin and E-cadherin.
      Transepithelial resistance was significantly decreased after both basolateral and
      apical exposure to IL-4. Permeability to 3 kDa dextran was also increased in IL-4
      exposed cells. Similar results were obtained with IL-13, but none of the innate
      type 2 cytokines examined (TSLP, IL-25 or IL-33) significantly affected barrier
      function. IL-4 and IL-13-induced barrier dysfunction was accompanied by reduced
      expression of membrane AJC components but not by induction of claudin- 2.
      Enhanced permeability caused by IL-4 was not affected by wortmannin, an inhibitor
      of PI3 kinase signaling, but was attenuated by a broad spectrum inhibitor of
      janus associated kinases. Our study indicates that IL-4 and IL-13 have disruptive
      effect on airway epithelial barrier function. Th2-cytokine induced epithelial
      barrier dysfunction may contribute to airway inflammation in allergic asthma. 

PMID- 24665391
TI  - Roles of the cellular prion protein in the regulation of cell-cell junctions and
      barrier function.
AB  - The cellular prion protein was historically characterized owing to its misfolding
      in prion disease. Although its physiological role remains incompletely
      understood, PrP(C) has emerged as an evolutionary conserved, multifaceted protein
      involved in a wide-range of biological processes. PrP(C) is a GPI-anchored
      protein targeted to the plasma membrane, in raft microdomains, where its
      interaction with a repertoire of binding partners, which differ depending on cell
      models, mediates its functions. Among identified PrP(C) partners are cell
      adhesion molecules. This review will focus on the multiple implications of PrP(C)
      in cell adhesion processes, mainly the regulation of cell-cell junctions in
      epithelial and endothelial cells and the consequences on barrier properties. We
      will show how recent findings argue for a role of PrP(C) in the recruitment of
      signaling molecules, which in turn control the targeting or the stability of
      adhesion complexes at the plasma membrane. 

PMID- 24665392
TI  - Trends in drug delivery through tissue barriers containing tight junctions.
AB  - A limitation in the uptake of many drugs is the restricted permeation through
      tissue barriers. There are two general ways to cross barriers formed by cell
      layers: by transcytosis or by diffusion through the intercellular space. In the
      latter, tight junctions (TJs) play the decisive role in the regulation of the
      barrier permeability. Thus, transient modulation of TJs is a potent strategy to
      improve drug delivery. There have been extensive studies on surfactant-like
      absorption enhancers. One of the most effective enhancers found is sodium
      caprate. However, this modulates TJs in an unspecific fashion. A novel approach
      would be the specific modulation of TJ-associated marvel proteins and claudins,
      which are the main structural components of the TJs. Recent studies have
      identified synthetic peptidomimetics and RNA interference techniques to
      downregulate the expression of targeted TJ proteins. This review summarizes
      current progress and discusses the impact on TJs' barrier function. 

PMID- 24665394
TI  - Netrin-1 guides inflammatory cell migration to control mucosal immune responses
      during intestinal inflammation.
AB  - The intestinal epithelium is a dynamic barrier playing an active role in
      intestinal homeostasis and inflammation. Intestinal barrier function is
      dysregulated during inflammatory bowel disease (IBD), with epithelial cells
      playing a significant part in generating an inflammatory milieu through the
      release of signals that attract leukocytes to the intestinal lamina propria.
      However, it is increasingly appreciated that the intestinal epithelium mediates a
      counterbalancing response to drive resolution. Drawing analogies with neuronal
      development, where the balance of chemoattractive and chemorepellent signals is
      key to directed neuronal movement it has been postulated that such secreted cues
      play a role in leukocyte migration. Netrin-1 is one of the best-described
      neuronal guidance molecules, which has been shown to play a significant role in
      directed migration of leukocytes. Prior to our study the potential role of netrin
      1 in IBD was poorly characterized. We defined netrin-1 as an intestinal
      epithelial-derived protein capable of limiting neutrophil recruitment to
      attenuate acute colitis. Our study highlights that the intestinal epithelium
      releases factors during acute inflammation that are responsible for fine-tuning
      the immune response. Exploration of these epithelial-mediated protective
      mechanisms will shed light on the complexity of the intestinal epithelial barrier
      in health and disease. 

PMID- 24665393
TI  - Cleavage of transmembrane junction proteins and their role in regulating
      epithelial homeostasis.
AB  - Epithelial tissues form a selective barrier that separates the external
      environment from the internal tissue milieu. Single epithelial cells are densely
      packed and associate via distinct intercellular junctions. Intercellular junction
      proteins not only control barrier properties of the epithelium but also play an
      important role in regulating epithelial homeostasis that encompasses cell
      proliferation, migration, differentiation and regulated shedding. Recent studies
      have revealed that several proteases target epithelial junction proteins during
      physiological maturation as well as in pathologic states such as inflammation and
      cancer. This review discusses mechanisms and biological consequences of
      transmembrane junction protein cleavage. The influence of junction protein
      cleavage products on pathogenesis of inflammation and cancer is discussed. 

PMID- 24665395
TI  - Understanding epithelial homeostasis in the intestine: An old battlefield of
      ideas, recent breakthroughs and remaining controversies.
AB  - The intestinal epithelium constitutes the barrier between the gut lumen and the
      rest of the body and a very actively renewing cell population. The crypt/villus
      and crypt/cuff units of the mouse small intestine and colon are its basic
      functional units. The field is confronted with competing concepts with regard to
      the nature of the cells that are responsible for all the day-to day cell
      replacement and those that act to regenerate the tissue upon injury and with two
      diametrically opposed models for lineage specification. The review revisits
      groundbreaking pioneering studies to provide non expert readers and crypt
      watchers with a factual analysis of the origins of the current models deduced
      from the latest spectacular advances. It also discusses recent progress made by
      addressing these issues in the crypts of the colon, which need to be better
      understood, since they are the preferred sites of major pathologies. 

PMID- 24665397
TI  - Claudin family members exhibit unique temporal and spatial expression boundaries
      in the chick embryo.
AB  - The claudin family of proteins are integral components of tight junctions and are
      responsible for determining the ion specificity and permeability of paracellular
      transport within epithelial and endothelial cell layers. Several members of the
      claudin family have been shown to be important during embryonic development and
      morphogenesis. However, detailed embryonic expression patterns have been
      described for only a few claudins. Here, we provide a phylogenetic analysis of
      the chicken claudins and a comprehensive analysis of their mRNA expression
      profiles. We found that claudin family members exhibit both overlapping and
      unique expression patterns throughout development. Especially striking were the
      distinct expression boundaries observed between neural and non-neural ectoderm,
      as well as within ectodermal derivatives. Claudins were also expressed in
      endodermally-derived tissues, including the anterior intestinal portal, pharynx,
      lung and pancreas and in mesodermally derived tissues such as the kidney, gonad
      and heart. The overlapping zones of claudin expression observed in the chick
      embryo may confer distinct domains of ion permeability within the early epiblast
      and in epithelial, mesodermal and endothelial derivatives that may ultimately
      influence embryonic patterning and morphogenesis during development. 

PMID- 24665396
TI  - Beyond cell-cell adhesion: Emerging roles of the tight junction scaffold ZO-2.
AB  - Zonula occludens proteins (ZO-1, ZO-2, ZO-3), which belong to the family of
      membrane-associated guanylate kinase (MAGUK) homologs, serve as molecular hubs
      for the assembly of multi-protein networks at the cytoplasmic surface of
      intercellular contacts in epithelial and endothelial cells. These multi-PDZ
      proteins exert crucial functions in the structural organization of intercellular
      contacts and in transducing intracellular signals from the plasma membrane to the
      nucleus. The junctional MAGUK protein ZO-2 not only associates with the C
      terminal PDZ-binding motif of various transmembrane junctional proteins but also
      transiently targets to the nucleus and interacts with a number of nuclear
      proteins, thereby modulating gene expression and cell proliferation. Recent
      evidence suggests that ZO-2 is also involved in stress response and
      cytoprotective mechanisms, which further highlights the multi-faceted nature of
      this PDZ domain-containing protein. This review focuses on ZO-2 acting as a
      molecular scaffold at the cytoplasmic aspect of tight junctions and within the
      nucleus and discusses additional aspects of its cellular activities. The
      multitude of proteins interacting with ZO-2 and the heterogeneity of proteins
      either influencing or being influenced by ZO-2 suggests an exceptional functional
      capacity of this protein far beyond merely serving as a structural component of
      cellular junctions. 

PMID- 24665398
TI  - Differential pathways of claudin oligomerization and integration into tight
      junctions.
AB  - Tight junctions are the critical intercellular structure required to establish an
      epithelial barrier. Among the several classes of proteins required to form tight
      junctions are the tetraspan transmembrane proteins known as claudins that
      directly determine paracellular permeability. Considerable progress has been made
      in understanding how incorporation of different claudins into tight junctions
      increase or decrease paracellular permeability and ion selectivity. However, it
      has proven difficult to identify discrete steps in claudin assembly and whether
      claudins exist in distinct oligomerization states prior to tight junction
      assembly. Studies of homomeric and heteromeric claudin-claudin interactions using
      complementary techniques suggest a diversity of pathways used by different
      claudins to oligomerize and integrate into tight junctions. 

PMID- 24665400
TI  - Barriers of the peripheral nerve.
AB  - This review introduces the traditionally defined anatomic compartments of the
      peripheral nerves based on light and electron microscopic topography and then
      explores the cellular and the most recent molecular basis of the different
      barrier functions operative in peripheral nerves. We also elucidate where, and
      how, the homeostasis of the normal human peripheral nerve is controlled in situ
      and how claudin-containing tight junctions contribute to the barriers of
      peripheral nerve. Also, the human timeline of the development of the barriers of
      the peripheral nerve is depicted. Finally, potential future therapeutic
      modalities interfering with the barriers of the peripheral nerve are discussed. 

PMID- 24665399
TI  - Regulation of claudins in blood-tissue barriers under physiological and
      pathological states.
AB  - Claudins are pivotal building blocks of tight junctions that form the
      paracellular barrier in epithelia and endothelia. In mammals, claudins are a 27
      gene family that encodes tetraspan membrane proteins, playing a crucial role in
      the formation and integrity of tight junctions and regulate the barrier function.
      Claudin isoforms are expressed in a tissue- and/or developmental stage-dependent
      manner. A growing body of evidence indicates that pathological states
      characterized by neuroinflammation, such as Alzheimer disease, multiple
      sclerosis, diabetic retinopathy and retinopathy of prematurity share a common
      feature: the barrier breakdown. This review aims integrating and summarizing the
      most relevant and recent work developed in the field of claudins, with particular
      attention to their role in blood-brain and blood-retinal barriers, as well as
      describing their regulation in the aforementioned human diseases. 

PMID- 24665401
TI  - Claudin interactions in and out of the tight junction.
AB  - Claudins form the paracellular tight junction seal in epithelial tissues.
      Although there is still limited information on how these proteins are organized
      at the junction, a number of recent studies have provided useful insights both
      into claudin-claudin interactions and into interactions between claudins and
      other proteins. The focus of this review is to summarize recent information about
      claudin interactions and to identify critical unanswered questions about claudin
      organization and tight junction structure which will be required to understand
      claudin function. 

PMID- 24665402
TI  - Claudins in teleost fishes.
AB  - Teleost fishes are a large and diverse animal group that represent close to 50%
      of all described vertebrate species. This review consolidates what is known about
      the claudin (Cldn) family of tight junction (TJ) proteins in teleosts. Cldns are
      transmembrane proteins of the vertebrate epithelial/endothelial TJ complex that
      largely determine TJ permeability. Cldns achieve this by expressing barrier or
      pore forming properties and by exhibiting distinct tissue distribution patterns.
      So far, ~63 genes encoding for Cldn TJ proteins have been reported in 16 teleost
      species. Collectively, cldns (or Cldns) are found in a broad array of teleost
      fish tissues, but select genes exhibit restricted expression patterns. Evidence
      to date strongly supports the view that Cldns play a vital role in the embryonic
      development of teleost fishes and in the physiology of tissues and organ systems
      studied thus far. 

PMID- 24665404
TI  - Claudin-20 promotes an aggressive phenotype in human breast cancer cells.
AB  - Claudin-20 is a member of the Claudin family of transmembrane proteins located in
      the tight junction (TJ) of cells of epithelial origin. Due to the increasing
      evidence supporting the role of TJ proteins in preventing tumor cell metastatic
      behavior, this study sought to evaluate the distribution of Claudin-20 in human
      breast cancer and the effect of Claudin-20 overexpression in human breast cancer
      cells. Q-PCR data from breast cancer primary tumors (n = 114) and matched
      background tissue (n = 30) showed that high claudin-20 expression was correlated
      with poor survival of patients with breast cancer (p = 0.022). Following
      transformation of the breast cancer cell lines MDA-MB-231 and MCF7 with a Claudin
      20 expression construct functional assays were performed to ascertain changes in
      cell behavior. Claudin-20 transformed cells showed significantly increased
      invasion (p < 0.005) and were significantly less adhesive than wild type cells (p
      < 0.05). There was no effect on growth (either in vitro or in vivo) for either
      cell line. Overexpression of Claudin-20 resulted in reduced transepithelial
      resistance (induced by the motogen HGF at 25 ng/ml, p = 0.0007). Interestingly,
      this was not mirrored by paracellular permeability, as overexpression of Claudin
      20 caused a decrease in permeability. The introduction of Claudin-20 into human
      breast cancer cells resulted in breast cancer cells with an aggressive phenotype
      and reduced trans-epithelial resistance. There was no corresponding decrease in
      paracellular permeability, indicating that this Claudin has a differential
      function in epithelial TJ. This provides further insight into the importance of
      correctly functioning TJ in preventing the progression of human breast cancer. 

PMID- 24665403
TI  - Claudins reign: The claudin/EMP/PMP22/gamma channel protein family in C. elegans.
AB  - The claudin family of integral membrane proteins was identified as the major
      protein component of the tight junctions in all vertebrates. Since their
      identification, claudins, and their associated pfam00822 superfamily of proteins
      have been implicated in a wide variety of cellular processes. Claudin homologs
      have been identified in invertebrates as well, including Drosophila and C.
      elegans. Recent studies demonstrate that the C. elegans claudins, clc-1-clc- 5,
      and similar proteins in the greater PMP22/EMP/claudin/voltage-gated calcium
      channel gamma subunit family, including nsy-4, and vab-9, while highly divergent
      at a sequence level from each other and from the vertebrate claudins, in many
      cases play roles similar to those traditionally assigned to their vertebrate
      homologs. These include regulating cell adhesion and passage of small molecules
      through the paracellular space, channel activity, protein aggregation,
      sensitivity to pore-forming toxins, intercellular signaling, cell fate
      specification and dynamic changes in cell morphology. Study of claudin
      superfamily proteins in C. elegans should continue to provide clues as to how
      claudin family protein function has been adapted to perform diverse functions at
      specialized cell-cell contacts in metazoans. 

PMID- 24665405
TI  - All about claudins.
AB  - Since the discovery of Claudins more than a decade ago, much has been learned
      about their structure-function relationships. Claudins are tetraspan membrane
      proteins responsible for the formation of tight junctions. In this capacity,
      Claudins form a tissue-specific selective permeability barrier that is critical
      for the function of the tissue. Claudins are developmentally regulated and
      expressed in a tissue- and cell-specific manner; chronic changes in their
      expression are associated with various disease states. The studies that have been
      put together in this Special Issue provide updates on both current knowledge as
      well as some of the unanswered questions and challenges in the field. 

PMID- 24665406
TI  - Tight junctions in human pancreatic duct epithelial cells.
AB  - Tight junctions of the pancreatic duct are essential regulators of physiologic
      secretion of the pancreas and disruption of the pancreatic ductal barrier is
      known to contribute to the pathogenesis of pancreatitis and progression of
      pancreatic cancer. Various inflammatory mediators and carcinogens can trigger
      tight junction disassembly and disruption of the pancreatic barrier, however
      signaling events that mediates such barrier dysfunctions remain poorly
      understood. This review focuses on structure and regulation of tight junctions in
      normal pancreatic epithelial cells and mechanisms of junctional disruption during
      pancreatic inflammation and cancer. We will pay special attention to a novel
      model of human telomerase reverse transcriptase-transfected human pancreatic
      ductal epithelial cells and will describe the roles of major signaling molecules
      such as protein kinase C and c-Jun N-terminal kinase in formation and disassembly
      of the pancreatic ductal barrier. 

PMID- 24665407
TI  - Barrier function of airway tract epithelium.
AB  - Airway epithelium contributes significantly to the barrier function of airway
      tract. Mucociliary escalator, intercellular apical junctional complexes which
      regulate paracellular permeability and antimicrobial peptides secreted by the
      airway epithelial cells are the three primary components of barrier function of
      airway tract. These three components act cooperatively to clear inhaled
      pathogens, allergens and particulate matter without inducing inflammation and
      maintain tissue homeostasis. Therefore impairment of one or more of these
      essential components of barrier function may increase susceptibility to infection
      and promote exaggerated and prolonged innate immune responses to environmental
      factors including allergens and pathogens resulting in chronic inflammation. Here
      we review the regulation of components of barrier function with respect to
      chronic airways diseases. 

PMID- 24665408
TI  - Build them up and break them down: Tight junctions of cell lines expressing
      typical hepatocyte polarity with a varied repertoire of claudins.
AB  - Tight junctions (TJs) of cells expressing simple epithelial polarity have been
      extensively studied, but less is known about TJs of cells expressing complex
      polarity. In this paper we analyzed, TJs of four different lines, that form bile
      canaliculi (BC) and express typical hepatocyte polarity; WIF-B9, 11-3, Can 3-1,
      Can 10. Striking differences were observed in claudin expression. None of the
      cell lines produced claudin-1. WIF-B9 and 11-3 expressed only claudin-2 while Can
      3-1 and Can 10 expressed claudin-2,-3,-4,-5. TJs of these two classes of lines
      differed in their ultra-stucture, paracellular permeability, and robustness.
      Lines expressing a large claudin repertoire, especially Can 10, had complex and
      efficient TJs, that were maintained when cells were depleted in calcium.
      Inversely, TJs of WIF-B9 and 11-3 were leaky, permissive and dismantled by
      calcium depletion. Interestingly, we found that during the polarization process,
      TJ proteins expressed by all lines were sequentially settled in a specific order:
      first occludin, ZO-1 and cingulin, then JAM-A and ZO-2, finally claudin-2.
      Claudins expressed only in Can lines were also sequentially settled: claudin-3
      was the first settled. Inhibition of claudin-3 expression delayed BC formation in
      Can10 and induced the expression of simple epithelial polarity. These results
      highlight the role of claudins in the settlement and the efficiency of TJs in
      lines expressing typical hepatocyte polarity. Can 10 seems to be the most
      promising of these lines because of its claudin repertoire near that of
      hepatocytes and its capacity to form extended tubular BC sealed by efficient TJs.

PMID- 24665409
TI  - Novel mechanism of cytokine-induced disruption of epithelial barriers: Janus
      kinase and protein kinase D-dependent downregulation of junction protein
      expression.
AB  - The ductal epithelium plays a key role in physiological secretion of pancreatic
      enzymes into the digestive system. Loss of barrier properties of the pancreatic
      duct may contribute to the development of pancreatitis and metastatic
      dissemination of pancreatic tumors. Proinflammatory cytokines are essential
      mediators of pancreatic inflammation and tumor progression; however, their
      effects on the integrity and barrier properties of the ductal epithelium have not
      been previously addressed. In the present study, we investigate mechanisms of
      cytokine-induced disassembly of tight junctions (TJs) and adherens junctions
      (AJs) in a model pancreatic epithelium. Exposure of HPAF-II human pancreatic
      epithelial cell monolayers to interferon (IFN)gamma disrupted integrity and
      function of apical junctions as manifested by increased epithelial permeability
      and cytosolic translocation of AJ and TJ proteins. Tumor necrosis factor
      (TNF)alpha potentiated the effects of IFNgamma on pancreatic epithelial
      junctions. The cytokine-induced increase in epithelial permeability and AJ/TJ
      disassembly was attenuated by pharmacological inhibition of Janus kinase (JAK)
      and protein kinase D (PKD). Loss of apical junctions in IFNgamma/TNFalpha-treated
      HPAF-II cells was accompanied by JAK and PKD dependent decrease in expression of
      AJ (E-cadherin, p120 catenin) and TJ (occludin, ZO-1) proteins. Depletion of E
      cadherin or p120 catenin recapitulated the effects of cytokines on HPAF-II cell
      permeability and junctions. Our data suggests that proinflammatory cytokines
      disrupt pancreatic epithelial barrier via expressional downregulation of key
      structural components of AJs and TJs. This mechanism is likely to be important
      for pancreatic inflammatory injury and tumorigenesis. 

PMID- 24665410
TI  - Aquaporin 5 regulates cigarette smoke induced emphysema by modulating barrier and
      immune properties of the epithelium.
AB  - Chronic obstructive pulmonary disease (COPD) causes significant morbidity and
      mortality. Cigarette smoke, the most common risk factor for COPD, induces airway
      and alveolar epithelial barrier permeability and initiates an innate immune
      response. Changes in abundance of aquaporin 5 (AQP5), a water channel, can affect
      epithelial permeability and immune response after cigarette smoke exposure. To
      determine how AQP5-derived epithelial barrier modulation affects epithelial
      immune response to cigarette smoke and development of emphysema, WT and AQP5(-/-)
      mice were exposed to cigarette smoke (CS). We measured alveolar cell counts and
      differentials, and assessed histology, mean-linear intercept (MLI), and surface
      to-volume ratio (S/V) to determine severity of emphysema. We quantified
      epithelial-derived signaling proteins for neutrophil trafficking, and manipulated
      AQP5 levels in an alveolar epithelial cell line to determine specific effects on
      neutrophil transmigration after CS exposure. We assessed paracellular
      permeability and epithelial turnover in response to CS. In contrast to WT mice,
      AQP5(-/-) mice exposed to 6 months of CS did not demonstrate a significant
      increase in MLI or a significant decrease in S/V compared with air-exposed mice,
      conferring protection against emphysema. After sub-acute (4 weeks) and chronic (6
      mo) CS exposure, AQP5(-/-) mice had fewer alveolar neutrophil but similar lung
      neutrophil numbers as WT mice. The presence of AQP5 in A549 cells, an alveolar
      epithelial cell line, was associated with increase neutrophil migration after CS
      exposure. Compared with CS-exposed WT mice, neutrophil ligand (CD11b) and
      epithelial receptor (ICAM-1) expression were reduced in CS-exposed AQP5(-/-)
      mice, as was secreted LPS-induced chemokine (LIX), an epithelial-derived
      neutrophil chemoattractant. CS-exposed AQP5(-/-) mice demonstrated decreased type
      I pneumocytes and increased type II pneumocytes compared with CS-exposed WT mice
      suggestive of enhanced epithelial repair. Absence of AQP5 protected against CS
      induced emphysema with reduced epithelial permeability, neutrophil migration, and
      altered epithelial cell turnover which may enhance repair. 

PMID- 24665411
TI  - Bile duct epithelial tight junctions and barrier function.
AB  - Bile ducts play a crucial role in the formation and secretion of bile as well as
      excretion of circulating xenobiotic substances. In addition to its secretory and
      excretory functions, bile duct epithelium plays an important role in the
      formation of a barrier to the diffusion of toxic substances from bile into the
      hepatic interstitial tissue. Disruption of barrier function and toxic injury to
      liver cells appear to be involved in the pathogenesis of a variety of liver
      diseases such as primary sclerosing cholangitis, primary biliary cirrhosis and
      cholangiocarcinoma. Although the investigations into understanding the structure
      and regulation of tight junctions in gut, renal and endothelial tissues have
      expanded rapidly, very little is known about the structure and regulation of
      tight junctions in the bile duct epithelium. In this article we summarize the
      current understanding of physiology and pathophysiology of bile duct epithelium,
      the structure and regulation of tight junctions in canaliculi and bile duct
      epithelia and different mechanisms involved in the regulation of disruption and
      protection of bile duct epithelial tight junctions. This article will make a case
      for the need of future investigations toward our understanding of molecular
      organization and regulation of canalicular and bile duct epithelial tight
      junctions. 

PMID- 24665413
TI  - HGF signaling regulates Claudin-3 dynamics through its C-terminal tyrosine
      residues.
AB  - The hormone HGF regulates morphogenesis and regeneration of multiple organs and
      increased HGF signaling is strongly associated with metastatic cancer. At the
      cellular level, one of the distinct effects of HGF is the de-stabilization of
      cell-cell junctions. Several molecular mechanisms have been shown to be involved
      that mostly culminate at the E-cadherin adhesion complex. One of the key
      determinants in HGF-driven morphological changes is the actomyosin cytoskeleton
      whose organization and physical parameters changes upon stimulation. Here we have
      investigated how HGF affects the different actomyosin-associated cell-cell
      junction complexes, Nectin Junctions, Adherens Junctions and Tight Junctions in
      MDCK cells. We find that components of all complexes stay present at cell-cell
      contacts until their physical dissociation. We find that at cell-cell junctions,
      the mobility of Claudin-3, but not that of other cell-cell adhesion receptors, is
      affected by HGF. This depends on tyrosine residues that likely affect PDZ-domain
      interactions at the C-terminal tail of Claudin-3, although their phosphorylation
      is not directly regulated by HGF. Thus we uncovered Claudins as novel targets of
      HGF signaling at cell-cell junctions. 

PMID- 24665414
TI  - Cognition in Late Life Depression: Treatment Considerations.
AB  - Late life depression (LLD) frequently presents with cognitive impairment, and
      growing evidence suggests that these disease processes are "linked" in multiple
      ways. For some individuals, LLD may be a recurrence of a long-standing depressive
      illness, while for others it may be the leading symptom of a developing
      neuropathological disorder. Overall, studies investigating the relationship
      between treatment of LLD and improvement in cognitive functioning have yielded
      mixed results. Research suggests that a subset of individuals with LLD and
      cognitive dysfunction will experience an improvement in cognitive function after
      antidepressant treatment, though a significant proportion will continue to
      exhibit cognitive impairment following resolution of their depressive symptoms.
      From a treatment standpoint, it is critical to ensure that an individual's
      depressive symptoms have been treated to remission, measured by a standardized
      rating scale such as the Geriatric Depression Scale (GDS). SSRI or SNRI
      monotherapy is often effective, and may be enhanced by employing an evidence
      based psychotherapy such as Problem Solving Therapy (PST) or Interpersonal
      Therapy (IPT), modified to accommodate cognitive impairments that may be present.
      With respect to specific treatment of cognitive dysfunction, cognitive
      augmentation or training strategies can be helpful for some patients, and may be
      explored in combination with treatment of the primary depressive episode. While
      the introduction of a cholinesterase inhibitor (e.g. donepezil) may be
      considered, the potential benefit (modest improvement in cognition and
      functioning) must be weighed against an increased risk for worsening or recurrent
      depression. Finally, lifestyle factors-such as aerobic exercise, follow-up with a
      primary care physician for management of co-morbid medical illnesses, and regular
      participation in stimulating activities (such as through a senior center)-are
      important and should be included as part of the overall treatment plan.

PMID- 24665416
TI  - The Editor's Role as a Harriet Shaw Weaver.

PMID- 24665415
TI  - High vitamin B12 levels are not associated with increased mortality risk for ICU
      patients after adjusting for liver function: a cohort study.
AB  - BACKGROUND AND AIMS: Recent research has suggested that high vitamin B12 levels
      may be associated with increased mortality after ICU admission. However, it is
      known that impaired liver function may lead to elevated B12 since B12 is
      metabolized through the liver, and therefore high B12 levels may serve as a proxy
      for poor liver function. The aim of this study is to assess the impact that liver
      function and liver disease have on the relationship between high vitamin B12
      levels and mortality in the ICU. METHODS: We performed an observational cohort
      study using ICU data that were collected from patients admitted to four ICU types
      (medical, surgical, cardiac care and cardiac surgery recovery) in one large urban
      hospital from 2001 to 2008. We analyzed the medical records of 1,684 adult
      patients (age >= 18 years) who had vitamin B12 and liver function measurements up
      to 14 days prior to ICU admission or within 24 hours after admission. RESULTS:
      While we found an association between high B12 and mortality when we did not
      control for any potential confounders, after we adjusted for liver function and
      liver disease, no significant association existed between B12 and mortality using
      multivariable logistic regression (30-day mortality: OR=1.18, 95% CI 0.81 to
      1.72, p=0.3890; 90-day mortality: OR=1.20, 95% CI 0.84 to 1.71, p=0.3077).
      CONCLUSIONS: Elevated B12 levels are not a significant predictor of mortality
      after ICU admission when liver function is controlled for, and may instead be a
      proxy for poor liver function.

PMID- 24665412
TI  - Ductal barriers in mammary epithelium.
AB  - Tissue barriers play an integral role in the biology and pathobiology of mammary
      ductal epithelium. In normal breast physiology, tight and adherens junctions
      undergo dynamic changes in permeability in response to hormonal and other
      stimuli, while several of their proteins are directly involved in mammary
      tumorigenesis. This review describes first the structure of mammary ductal
      epithelial barriers and their role in normal mammary development, examining the
      cyclical changes in response to puberty, pregnancy, lactation and involution. It
      then examines the role of adherens and tight junctions and the participation of
      their constituent proteins in mammary tumorigenic functions such as migration,
      invasion and metastasis. Finally, it discusses the potential of these adhesion
      proteins as both prognostic biomarkers and potential therapeutic targets in
      breast cancer. 

PMID- 24665417
TI  - Analysis of frequency of use of different scar assessment scales based on the
      scar condition and treatment method.
AB  - Analysis of scars in various conditions is essential, but no consensus had been
      reached on the scar assessment scale to select for a given condition. We reviewed
      papers to determine the scar assessment scale selected depending on the scar
      condition and treatment method. We searched PubMed for articles published since
      2000 with the contents of the scar evaluation using a scar assessment scale with
      a Journal Citation Report impact factor >0.5. Among them, 96 articles that
      conducted a scar evaluation using a scar assessment scale were reviewed and
      analyzed. The scar assessment scales were identified and organized by various
      criteria. Among the types of scar assessment scales, the Patient and Observer
      Scar Assessment Scale (POSAS) was found to be the most frequently used scale. As
      for the assessment of newly developed operative scars, the POSAS was most used.
      Meanwhile, for categories depending on the treatment methods for preexisting
      scars, the Vancouver Scar Scale (VSS) was used in 6 studies following a laser
      treatment, the POSAS was used in 7 studies following surgical treatment, and the
      POSAS was used in 7 studies following a conservative treatment. Within the 12
      categories of scar status, the VSS showed the highest frequency in 6 categories
      and the POSAS showed the highest frequency in the other 6 categories. According
      to our reviews, the POSAS and VSS are the most frequently used scar assessment
      scales. In the future, an optimal, universal scar scoring system is needed in
      order to better evaluate and treat pathologic scarring. 

PMID- 24665419
TI  - Effect of biopsy technique on the survival rate of malignant melanoma patients.
AB  - BACKGROUND: Cutaneous malignant melanoma has a poor prognosis. The detrimental
      effect of incisional biopsies on the outcome of malignant melanoma has been
      debated. The aim of this study was to determine the effect of the presence and
      type of biopsy on the prognosis of malignant melanoma. METHODS: The medical
      records of 109 malignant melanoma patients treated at Tokushima University
      Hospital from 1983 to 2007 were reviewed. After excluding 28 cases with stage 0
      disease or incomplete data, 81 cases were analyzed in detail with respect to
      patient sex, age, tumor site, clinical stage at diagnosis, presence of ulceration
      or lymph node metastasis, and prognosis. The five-year survival and five-year
      disease-free survival rates of patients who underwent incisional or excisional
      biopsies were compared with those who did not undergo a biopsy. RESULTS: The male
      to-female ratio was 1:1.19. The mean age was 61.3 years (range, 19-93 years). The
      most common site was a lower extremity, and the most common clinical stage was
      stage II. No significant differences in clinicopathological features, five-year
      survival rates, and five-year disease-free survival rates were observed among the
      three groups. CONCLUSIONS: The presence and type of biopsy neither affected the
      metastatic rate nor the prognosis of malignant melanoma. The use of incisional
      biopsies is not encouraged because tumor thickness cannot be measured accurately.
      However, they may be helpful for confirming the diagnosis if an excisional biopsy
      cannot be performed.

PMID- 24665418
TI  - Predictors of readmission after inpatient plastic surgery.
AB  - BACKGROUND: Understanding risk factors that increase readmission rates may help
      enhance patient education and set system-wide expectations. We aimed to provide
      benchmark data on causes and predictors of readmission following inpatient
      plastic surgery. METHODS: The 2011 National Surgical Quality Improvement Program
      dataset was reviewed for patients with both "Plastics" as their recorded surgical
      specialty and inpatient status. Readmission was tracked through the "Unplanned
      Readmission" variable. Patient characteristics and outcomes were compared using
      chi-squared analysis and Student's t-tests for categorical and continuous
      variables, respectively. Multivariate regression analysis was used for
      identifying predictors of readmission. RESULTS: A total of 3,671 inpatient
      plastic surgery patients were included. The unplanned readmission rate was 7.11%.
      Multivariate regression analysis revealed a history of chronic obstructive
      pulmonary disease (COPD) (odds ratio [OR], 2.01; confidence interval [CI], 1.12
      3.60; P=0.020), previous percutaneous coronary intervention (PCI) (OR, 2.69; CI,
      1.21-5.97; P=0.015), hypertension requiring medication (OR, 1.65; CI, 1.22-2.24;
      P<0.001), bleeding disorders (OR, 1.70; CI, 1.01-2.87; P=0.046), American Society
      of Anesthesiologists (ASA) class 3 or 4 (OR, 1.57; CI, 1.15-2.15; P=0.004), and
      obesity (body mass index >=30) (OR, 1.43; CI, 1.09-1.88, P=0.011) to be
      significant predictors of readmission. CONCLUSIONS: Inpatient plastic surgery has
      an associated 7.11% unplanned readmission rate. History of COPD, previous PCI,
      hypertension, ASA class 3 or 4, bleeding disorders, and obesity all proved to be
      significant risk factors for readmission. These findings will help to benchmark
      inpatient readmission rates and manage patient and hospital system expectations.

PMID- 24665421
TI  - Regional analysis of soft tissue thickness on korean buttocks and application to
      fasciocutaneous flap design.
AB  - BACKGROUND: Various shapes and designs of the gluteal artery perforator flap have
      been used for treating sacral pressure sores and reconstructing breasts. To
      establish the ideal fasciocutaneous flap design for use in the gluteal area, the
      soft tissue thickness distribution was measured. METHODS: Twenty-one buttocks of
      adult Korean cadavers were analyzed through rectangular subfascial dissection.
      Each buttock was divided horizontally into 10 sections and vertically into 10
      sections, and then, the thickness at the corners of the sections was measured.
      For the sake of comparison and statistical verification with living bodies,
      computed tomography (CT) images of 120 buttocks of patients were randomly
      selected. Five horizontal sections and 4 vertical sections were made, and the
      thickness at each corner was recorded. RESULTS: According to the dissection and
      the CT images, the area with the thinnest soft tissues in the buttock was around
      the posterior superior iliac spine, close to the sacral area. The thickest area
      was the superolateral area of the buttock, which was 3.24 times and 2.15 times
      thicker than the thinnest area in the studies on cadaver anatomy and the CT
      images, respectively. CONCLUSIONS: The thickness of the soft tissues in the
      buttocks differed by area. The superolateral area had the thickest soft tissues,
      and the superomedial area had the thinnest. This study includes information on
      the distribution of the thickness of the gluteal soft tissues of Koreans. The
      outcome of this study may contribute to the design of effective local flaps for
      pressure sore reconstruction and free flaps for breast reconstruction.

PMID- 24665420
TI  - A Simple Strategy in Avulsion Flap Injury: Prediction of Flap Viability Using
      Wood's Lamp Illumination and Resurfacing with a Full-thickness Skin Graft.
AB  - BACKGROUND: Extensive degloving injuries of the extremities usually result in
      necrosis of the flap, necessitating comprehensive skin grafting. Provided there
      is a sufficient tool to evaluate flap viability, full-thickness skin can be used
      from a nonviable avulsed flap. We used a Wood's lamp to determine the viability
      of avulsed flaps in the operation field after intravenous injection of
      fluorescein dye. METHODS: We experienced 13 cases during 16 months. Fifteen
      minutes after the intravenous injection of fluorescein dye, the avulsed skin
      flaps were examined and non-fluorescent areas were marked under Wood's lamp
      illumination. The marked area was defatted for full-thickness skin grafting. The
      fluorescent areas were sutured directly without tension. The non-fluorescent
      areas were covered by defatted skin. Several days later, there was soft tissue
      necrosis within the flap area. We measured necrotic area and revised the flap.
      RESULTS: Among all the cases, necrotic area was 21.3% of the total avulsed area.
      However, if we exclude three cases, one of a carelessly managed patient and two
      cases of the flaps were inappropriately applied, good results were obtained, with
      a necrotic area of only 8.4%. Eight patients needed split-thickness skin grafts,
      and heel pad reconstruction was performed with free flap. CONCLUSIONS: A full
      thickness skin graft from an avulsed flap is a good method for addressing
      aesthetic concerns without producing donor site morbidity. Fluorescein dye is a
      useful, simple, and cost-effective tool for evaluating flap viability. Avulsed
      flap injuries can be managed well with Wood's lamp illumination and a full
      thickness skin graft.

PMID- 24665422
TI  - Perforator flaps after excision of large epidermal cysts in the buttocks.
AB  - BACKGROUND: Epidermal cysts are commonly occurring masses usually less than 5 cm
      in diameter, but in predisposed patients, epidermal cysts can grow relatively
      large due to chronic infection. METHODS: From June 2002 to July 2010, 17 patients
      received 19 regional perforator-based island flaps to cover defects due to the
      excision of large epidermal cysts (diameter >5 cm) in the buttocks. Eight
      patients had diabetes, and seven had rheumatoid arthritis. The pedicles were not
      fully isolated to prevent spasms or twisting. RESULTS: All the flaps survived
      completely, except for one case with partial necrosis of the flap, which
      necessitated another perforator-based island flap for coverage. There were two
      cases of wound dehiscence, which were re-closed after meticulous debridement.
      There were no recurrences of the masses during follow-up periods of 8.1 months
      (range, 6-12 months). CONCLUSIONS: In patients with large epidermal cysts and
      underlying medical disorders, regional perforator-based island flaps can be the
      solution to coverage of the defects after excision.

PMID- 24665423
TI  - Free Flap Reconstruction of Head and Neck Defects after Oncologic Ablation: One
      Surgeon's Outcomes in 42 Cases.
AB  - BACKGROUND: Free flap surgery for head and neck defects has gained popularity as
      an advanced microvascular surgical technique. The aims of this study are first,
      to determine whether the known risk factors such as comorbidity, tobacco use,
      obesity, and radiation increase the complications of a free flap transfer, and
      second, to identify the incidence of complications in a radial forearm free flap
      and an anterolateral thigh perforator flap. METHODS: We reviewed the medical
      records of patients with head and neck cancer who underwent reconstruction with
      free flap between May 1994 and May 2012 at our department of plastic and
      reconstructive surgery. RESULTS: The patients included 36 men and 6 women, with a
      mean age of 59.38 years. The most common primary tumor site was the tongue (38%).
      The most commonly used free flap was the radial forearm free flap (57%), followed
      by the anterolateral thigh perforator free flap (22%). There was no occurrence of
      free flap failure. In this study, risk factors of the patients did not increase
      the occurrence of complications. In addition, no statistically significant
      differences in complications were observed between the radial forearm free flap
      and anterolateral thigh perforator free flap. CONCLUSIONS: We could conclude that
      the risk factors of the patient did not increase the complications of a free flap
      transfer. Therefore, the risk factors of patients are no longer a negative factor
      for a free flap transfer.

PMID- 24665424
TI  - Microsurgery: the top 50 classic papers in plastic surgery: a citation analysis.
AB  - BACKGROUND: The number of citations that a published article has received
      reflects the importance of the paper in the particular area of practice. In
      microsurgery, thus far, which journal articles are cited most frequently is
      unknown. The purpose of this study was to identify and analyze the
      characteristics of the top 50 papers in the field of microsurgery in the plastic
      surgery literature. METHODS: The 50 most cited papers published in high impact
      plastic surgery and microsurgery journals were identified. The articles were
      ranked in the order of the number of citations received. These 50 classic papers
      were analyzed for article type, journal distribution, and geographic and
      institutional origin. RESULTS: Six international journals contributed to the top
      50 papers in microsurgery. The most cited paper reported on the early use of the
      vascularized bone graft and was cited 116 times. The top 50 papers originated
      from just 10 countries with the United States producing the most. The Preston and
      Northcote Community Hospital, Melbourne published 5 papers and this was the most
      productive institution in the top 50. CONCLUSIONS: These papers represent many
      important milestones in the relatively short history of microsurgery.
      Furthermore, our citation analysis provides useful information to budding authors
      as to what makes a paper attain a "classic" status.

PMID- 24665425
TI  - Nipple reconstruction with rolled dermal graft support.
AB  - BACKGROUND: Loss of nipple projection is a common problem following nipple
      reconstruction. The aim of this study was to demonstrate that the use of a
      tightly rolled dermal graft is effective in the long-term maintenance of nipple
      projection. METHODS: Nipple reconstruction was performed using the C-V flap
      technique. A dermal graft was harvested from the dog-ear portion of previous
      scars. The graft was rolled tightly into a compact cylinder and used to augment
      the nipple reconstruction. Postoperatively, stacked Allevyn dressing was used for
      protecting the nipple from compression for a minimum of two months. Nipple
      projection was measured at the time of surgery and at 12 months postoperatively.
      RESULTS: Forty nipple reconstructions were performed using this technique. There
      were 19 transverse rectus abdominis musculocutaneous (TRAM) flaps, 10 latissimus
      dorsi (LD) flaps, and 11 tissue-expanded breast mounds. At one year, the mean
      projection was 0.80 cm (range, 0.62-1.22 cm). The twelve-month average
      maintenance of nipple projection was 70.2% for the TRAM flap group, 76.3% for the
      LD flap group, and 61.8% for the tissue-expanded group. In two patients with
      previous irradiation of the reconstructed breasts, relatively poor maintenance of
      nipple projection was noted (45.7%). No complications were noted, and all of the
      donor sites healed well primarily. CONCLUSIONS: Our results demonstrated that the
      use of a C-V flap with a tightly rolled dermal graft for nipple reconstruction
      improves the long-term maintenance of nipple projection. Its advantages include
      reproducibility, technical simplicity, cost-effectiveness, and minimal donor site
      morbidity.

PMID- 24665426
TI  - Analysis of the development of the nasal septum and measurement of the
      harvestable septal cartilage in koreans using three-dimensional facial bone
      computed tomography scanning.
AB  - BACKGROUND: The septal cartilage is the most useful donor site for autologous
      cartilage graft material in rhinoplasty. For successful nasal surgery, it is
      necessary to understand the developmental process of the nasal septum and to
      predict the amount of harvestable septal cartilage before surgery. METHODS: One
      hundred twenty-three Korean patients who underwent three-dimensional (3D) facial
      bone computed tomography (CT) were selected for evaluation of the midsagittal
      view of the nasal septum. Multiple parameters such as the area of each component
      of the nasal septum and the amount of harvestable septal cartilage were measured
      using Digimizer software. RESULTS: The area of the total nasal septum showed
      rapid growth until the teenage years, but thereafter no significant change
      throughout the lifetime. However, the development of the septal cartilage showed
      a gradual decline due to ossification changes with aging after puberty in spite
      of a lack of change in the total septal area. The area of harvestable septal
      cartilage in young adults was 549.84+/-151.26 mm(2) and decreased thereafter with
      age. CONCLUSIONS: A 3D facial bone CT scan can provide valuable information on
      the septal cartilage graft before rhinoplasty. Considering the developmental
      process of the septal cartilage identified in this study, septal surgery should
      not be performed until puberty due to the risk of nasal growth impairment.
      Furthermore, in elderly patients who show a decreased cartilage area due to
      ossification changes, septal cartilage harvesting should be performed carefully
      due to the risk of saddle nose deformity.

PMID- 24665427
TI  - A preoperative marking template for deep inferior epigastric artery perforator
      flap perforators in breast reconstruction.
AB  - Preoperative perforator marking for deep inferior epigastric artery perforator
      flaps is vital to the success of the procedure in breast reconstruction. Advances
      in imaging have facilitated accurate identification and preselection of
      potentially useful perforators. However, the reported imaging accuracy may be
      lost when preoperatively marking the patient, due to 'mapping errors', as this
      relies on the use of 2 reported vectors from a landmark such as the umbilicus.
      Observation errors have been encountered where inaccurate perforator vector
      measurements have been reported in relation to the umbilicus. Transcription
      errors have been noted where confusing and wordy reports have been typed or where
      incorrect units have been given (millimetres vs. centimetres). Interpretation
      errors have also occurred when using the report for preoperative marking.
      Furthermore, the marking process may be unnecessarily time-consuming. We describe
      a bespoke template, created using an individual computed tomography angiography
      image, that increases the efficiency and accuracy of preoperative marking. The
      template is created to scale, is individually tailored to the patient, and is
      particularly useful in cases where multiple potential suitable perforators exist.

PMID- 24665428
TI  - Facial transplantation surgery.

PMID- 24665429
TI  - Multiple sparganosis.

PMID- 24665430
TI  - Tracheal laceration related to endotracheal intubation.

PMID- 24665431
TI  - Surgical resection of acquired vulvar lymphangioma circumscriptum.

PMID- 24665432
TI  - An unexpected complication after periorbital tumor surgery in a patient later
      discovered to have myelodysplasia.

PMID- 24665433
TI  - Patient with psychosis undergoing cheek reconstruction.

PMID- 24665434
TI  - Thumb carpometacarpal dislocation and open dorsal metacarpophalangeal
      instability: a variation of the floating thumb.

PMID- 24665436
TI  - Aberrant p16INK4A methylation: Relation to viral related chronic liver disease
      and hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is currently the fifth most common
      solid tumor worldwide and the third leading cause of cancer related deaths.
      Several studies have shown that the tumor suppressor gene p16INK4A is frequently
      downregulated by aberrant methylation of the 5'-cytosine-phosphoguanine island
      within the promoter region. AIM: To find out the frequency of methylated p16INK4A
      in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in
      hepatocarcinogenesis. PATIENTS AND METHODS: This study was performed on 58
      subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers.
      Methylation of p16INK4A was examined using methylation specific polymerase chain
      reaction (PCR) (MSP). Comparison of quantitative variables between the study
      groups was done using Mann-Whitney U test for independent samples when not
      normally distributed. For comparing categorical data, Chi-square (chi(2)) test
      was performed. Exact test was used instead when the expected frequency was less
      than 5. RESULTS: Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of
      liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the
      p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV)
      antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A
      methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000
      MUg/mL). There were no significant associations between the status of p16INK4A
      methylation and tumor size. CONCLUSION: Hypermethylation of p16INK4A was found to
      be infrequent among Egyptian patients with HCC.

PMID- 24665435
TI  - Locally harvested foods support serum 25-hydroxyvitamin D sufficiency in an
      indigenous population of Western Alaska.
AB  - BACKGROUND: Low serum vitamin D is associated with higher latitude, age, body fat
      percentage and low intake of fatty fish. Little documentation of vitamin D
      concentrations is available for Alaska Native populations. OBJECTIVE: This study
      was undertaken to investigate serum 25-hydroxyvitamin D (25(OH)D) concentrations
      of the Yup'ik people of southwestern Alaska in relation to demographic and
      lifestyle variables, particularly with the use of locally harvested (local)
      foods. DESIGN: Cross-sectional study. METHODS: We estimated 25(OH)D, dietary
      vitamin D and calcium, percent of energy from local foods and demographic
      variables in 497 Yup'ik people (43% males) aged 14-92 residing in southwestern
      Alaska. Sampling was approximately equally divided between synthesizing and non
      synthesizing seasons, although the preponderance of samples were drawn during
      months of increasing daylight. RESULTS: Mean vitamin D intake was 15.1 +/- 20.2
      ug/d, while local foods accounted for 22.9 +/- 17.1% of energy intake. The
      leading sources of vitamin D were local fish (90.1%) followed by market foods.
      Mean 25(OH)D concentration was 95.6 +/- 40.7 nmol/L. Participants in the upper
      50th percentile of 25(OH)D concentration tended to be older, male, of lower body
      mass index, sampled during the synthesizing season, and among the upper 50th
      percentile of local food use. CONCLUSIONS: A shift away from locally harvested
      foods will likely increase the risk for serum 25(OH)D insufficiency in this
      population.

PMID- 24665437
TI  - Acute radiation toxicity in head and neck and lung malignancies.

PMID- 24665438
TI  - Role of oral glutamine in alleviation and prevention of radiation-induced oral
      mucositis: A prospective randomized study.
AB  - BACKGROUND: Oral mucositis is the most frequently occurring painful and dose
      limiting side-effect of radiation of the head and neck region. Few studies
      demonstrated that oral glutamine suspension may significantly reduce the duration
      and severity of objective oral mucositis during radiotherapy. MATERIALS AND
      METHODS: A randomized, prospective single institutional case control study was
      performed between April 2012 and November 2012 comparing the influence of oral
      glutamine on radiation induced mucositis in head and neck malignancy patients.
      Seventy biopsy proven patients with head and neck cancer receiving primary or
      adjuvant radiation therapy were randomized to receive either oral glutamine
      suspension daily 2h before radiation in the study arm (10 g in 1000 ml of water)
      (n = 35) or nothing before radiation; control arm (n = 35). RESULTS AND ANALYSIS:
      Total 32 patients (91.43%) in the glutamine arm and total 34 patients (97.15%)
      developed mucositis. Grade 3 mucositis (14.29%) and grade 4 mucositis (2.86%) in
      the study arm (who received oral glutamine) were significantly less (P = 0.02 and
      P = 0.04, respectively) in the glutamine arm. The mean duration of grade 3 or
      worse mucositis (grade 3 and grade 4) was significantly less (6.6 days vs. 9.2
      days) in study arm with P < 0.001. Mean time of onset of mucositis was
      significantly delayed in patients who took glutamine in comparison to control arm
      with P < 0.001. CONCLUSION: Glutamine delays oral mucositis in the head neck
      cancer patients. Moreover, it reduces the frequency and duration of grade 3 and
      grade 4 mucositis.

PMID- 24665440
TI  - Radiation oncology: Colors and hues.

PMID- 24665439
TI  - Ipsilateral lung dose volume parameters predict radiation pneumonitis in addition
      to classical dose volume parameters in locally advanced NSCLC treated with
      combined modality therapy.
AB  - PURPOSE: The purpose was to determine the correlation of clinical factors and
      lung dose volume parameters with significant radiation pneumonitis (RP) in non
      small cell lung cancer patients treated with combined modality therapy. MATERIALS
      AND METHODS: Between January 2008 and December 2010, 52 patients of non-small
      cell lung cancer were treated with combined modality therapy with radical intent.
      Radiation pneumonitis was correlated with ipsilateral (V20 ipsi, V5 ipsi and MLD
      ipsi) and whole lung (V20, V5, and MLD) dose volume parameters. Clinical factors
      like pulmonary function tests (PFT), site of tumor, planning target volume, and
      type of treatment were also correlated with incidence of significant pneumonitis.
      RESULTS: Out of 52 patients, 35.3% developed grade 2 or more pneumonitis. On
      univariate analysis, factors significantly correlating with radiation pneumonitis
      were V5 (P = 0.002), V5 ipsi (P = 0.000), V20 (P = 0.019), V20 ipsi (P = 0.004),
      MLD (P = 0.008) and MLD ipsi (P = 0.008). On multivariate analysis, V5 ipsi was
      retained as the most significant factor. Concurrent chemoradiation caused
      significantly more RP than neoadjuvant chemoradiation (P = 0.004). A cutoff of
      65% for V5 ipsi had a sensitivity of 65% and a specificity of 91%. CONCLUSION:
      The correlation between pneumonitis and dosimetric constraints has been
      validated. Adding ipsilateral V20, V5, and MLD to the classical total lung
      constraints identifies patients likely to develop pulmonary toxicity in patients
      undergoing chemoradiation.

PMID- 24665441
TI  - A dosimetric study of volumetric modulated arc therapy planning techniques for
      treatment of low-risk prostate cancer in patients with bilateral hip prostheses.
AB  - BACKGROUND AND PURPOSE: Recently, megavoltage (MV) photon volumetric modulated
      arc therapy (VMAT) has gained widespread acceptance as the technique of choice
      for prostate cancer patients undergoing external beam radiation therapy. However,
      radiation treatment planning for patients with metallic hip prostheses composed
      of high-Z materials can be challenging due to (1) presence of streak artifacts
      from prosthetic hips in computed tomography dataset, and (2) inhomogeneous dose
      distribution within the target volume. The purpose of this study was to compare
      the dosimetric quality of VMAT techniques in the form of Rapid Arc (RA) for
      treating low-risk prostate cancer patient with bilateral prostheses. MATERIALS
      AND METHODS: Three treatment plans were created using RA techniques utilizing 2
      arcs (2-RA), 3 arcs (3-RA), and 4 arcs (4-RA) for 6 MV photon beam in Eclipse
      treatment planning system. Each plan was optimized for total dose of 79.2 Gy
      prescribed to the planning target volume (PTV) over 44 fractions. All three RA
      plans were calculated with anisotropic analytical algorithm. RESULTS: The mean
      and maximum doses to the PTV as well as the homogeneity index among all three RA
      plans were comparable. The plan conformity index was highest in the 2-Arc plan
      (1.19) and lowest in the 4-Arc plan (1.10). In comparison to the 2-RA technique,
      the 4-RA technique reduced the doses to rectum by up to 18.8% and to bladder by
      up to 7.8%. In comparison to the 3-RA technique, the 4-RA technique reduced the
      doses to rectum by up to 14.6% and to bladder by up to 3.5%. CONCLUSION: Based on
      the RA techniques investigated for a low-risk prostate cancer patient with
      bilateral prostheses, the 4-RA plan produced lower rectal and bladder dose and
      better dose conformity across the PTV in comparison with the 2-RA and 3-RA plans.

PMID- 24665442
TI  - Prescribed dose versus calculated dose of spinal cord in standard head and neck
      irradiation assessed by 3-D plan.
AB  - BACKGROUND AND PURPOSE: Spinal cord toxicity can be dreaded complication while
      treating head and neck cancer by conventional radiotherapy. Cord sparing approach
      is applied by two phase planning in conventional head neck radiotherapy. In spite
      of cord sparing approach spinal cord still receives considerable scatter dose.
      Our study aims to do the volumetric analysis of spinal cord dosimetry and to
      correlate with the clinical findings. MATERIALS AND METHODS: Treatment planning
      was done in two phases. First phase treatment fields include gross disease- both
      tumor and involved nodes. in the second phase, treatment field shrinkage was done
      to cover the gross disease sparing the spinal cord. These fields are termed as
      off-cord fields. 42 patients with histological proven squamous cell carcinoma of
      the head and neck region were analysed with two groups. In Group A, 46 Gy was
      given in 23 fractions, and then tumor-boost with off-cord field received 24 Gy in
      12 fractions. In Group B 50 Gy was prescribed in 25 fractions initially, then off
      cord field given 20 Gy in 10 fractions to analyze theoutcome. Planning Computed
      tomography (CT) scan was done Philips Brilliance 16 slice CT scan machine, and
      contouring and dose calculation were done at ASHA treatment planning software.
      RESULTS: Maximum dose and dose at 1 cm3, 2 cm3, and 5 cm3 were calculated.
      Maximum dose to cord was 52.6 Gy (range 48.1-49.7 Gy) in Group A and 54.3 Gy
      (range 51.48-52.33 Gy) in Group B initially. Off-cord fields received mean dose
      8.07 Gy (85.85% of maximum) in Group A and 5.47 Gy (86.84% of maximum) in Group
      B. At the end of 6 months from the last date of radiotherapy, grade 1 spinal cord
      toxicity found in two patients in Group A and one patient in Group B respectively
      (P = 0.55). Both groups received additional dose, which are higher than the
      prescribed dose, but no patients show significant spinal cord toxicity after 6
      month of follow-up. CONCLUSION: Spinal cord received scatter dose which much
      higher than the predicted dose in conventional radiotherapy of head neck cancer.
      Short term follow up failed to establish clinical correlation with volumetric
      dose of spinal cord. Two phase cord sparing head neck radiation planning if
      practiced should be used with caution.

PMID- 24665443
TI  - Hemi body irradiation: An economical way of palliation of pain in bone metastasis
      in advanced cancer.
AB  - BACKGROUND: The primary aim of this prospective non-randomized study was to
      evaluate the effect of hemi-body irradiation (HBI) on pain and quality of life in
      cancer patients with extensive bone metastases. The secondary aim was to evaluate
      side-effects and cost-effectiveness of the treatment. MATERIALS AND METHODS:
      Between March 2008 and December 2010, a total of 23 (male = 14, female = 9,
      median age = 60 years) diagnosed cases of metastatic cancer patients (prostate =
      11, breast = 6, and lung = 6) received HBI, which was delivered as lower (n = 7)
      (dose = 8 Gy), upper (n = 8) (dose = 6 Gy), or sequential HBI (n = 8) with a
      Telecobalt unit (Theratron 780C). Among them, one lung cancer patient died at 2
      months and one prostate cancer patient defaulted after the second follow-up.
      Thus, 21 patients (male = 13, female = 8, median age = 65 years) (prostatic
      cancer = 10, breast cancer = 6, and lung cancer = 5) were followed up for a
      minimum of 6 months. Evaluations were performed before and at 2, 4, 8, 16, and 24
      weeks after treatment. Pain evaluation was done by Visual Analogue Scale (VAS),
      Verbal Rating Scale (VRS), Percentage of Pain Relief (PRR), and Global Pain Score
      (GPS). Toxicity was assessed by CTC v-3 toxicity scores in the medical record.
      Assessment of oral morphine consumption was done before and after radiation using
      paired t-test, and correlation analysis was also done with decrease of morphine
      consumption and reduction of pain score using statistical analysis. RESULTS:
      Response (control of pain) was partial (PR) in 67% and complete (CR) in 22% of
      patients. For most patients, the pain control lasted throughout the follow-up
      period (6 months). From 66.66% patients requiring 13 or more Morphine (10 mg)
      tablets per day prior to HBI, none of the patients required to consume 13 or more
      Morphine (10 mg) tablets per day following HBI, which was correlated with
      significant reduction in various pain scores (P < 0.05). One way ANOVA with
      Dunnett's Multiple Comparison Test (P < 0.05) was significant in VAS score
      changes, VRS score changes, PPR score changes, and GPS score changes. Along with
      the decrease in morphine tablets, the Linear Correlation of various scales for
      pain reduction like VAS, VRS, PPR, and GPS were significant. As such, the quality
      of life was better due to decreased pain and also, a decrease in the dose of
      analgesics. Grade 1 and 2 hematological toxicity and grade 1 diarrhea were
      observed as common side-effects. The average total cost of treatment including
      hospital stay, medicines, and radiation charges was around INR 400.00.
      CONCLUSION: This study shows that hemibody irradiation is not only an effective
      modality for palliation of severe bone pain in advanced cancer cases but also
      economical, involves short hospital stay, with acceptable side-effects, utilizes
      the simple Telecobalt machine, and is less cumbersome in comparison to other
      currently available pain palliation methods like oral morphine and
      radiopharmaceuticals.

PMID- 24665444
TI  - Gestational trophoblastic neoplasia: A 6 year retrospective study.
AB  - AIMS AND OBJECTIVES: To study the clinical presentations of gestational
      trophoblastic neoplasia and its response to chemotherapy. MATERIALS AND METHODS:
      This is a retrospective study of 28 women of gestational trophoblastic neoplasia
      evaluated over a period of 6 years from January 2004 to December 2009. Patients
      were evaluated on the basis of their age, number of deliveries, history of
      abortion or molar pregnancy, and the treatment received. All patients were scored
      on the basis of WHO scoring system. Patients with low risk (score </=6) received
      single agent chemotherapy with methotrexate or actinomycin D. Patients with high
      risk (score >/=7) received multiple agent chemotherapy with EMACO regimen. After
      completion of chemotherapy patients were followed for a minimum of 2 years. The
      response to treatment was evaluated during follow-up by clinical examination,
      beta hCG levels and imaging as and when required. RESULTS: Out of 28 women only
      27 could be evaluated, because 1 patient was lost to follow-up. Out of 27
      patients, 18 patients (66.67%) achieved complete remission with the first-line
      chemotherapy and additional 25.92% (7/27) achieved complete remission with second
      line chemotherapy resulting in complete remission of 92.5% (25/27). CONCLUSION:
      Gestational trophoblastic neoplasia is curable if patient is properly evaluated
      and scored. It shows good response to chemotherapy.

PMID- 24665445
TI  - Assessment of nutritional status of gynecological cancer cases in India and
      comparison of subjective and objective nutrition assessment parameters.
AB  - AIM: To assess the nutritional status of gynecological cancer patients using
      scored Patient Generated Subjective Global Assessment (PG-SGA) then compare it
      with the body mass index (BMI), hemoglobin, serum albumin, and approximate
      percentage weight lost in last 1 month so as to find any one parameter that can
      be used in place of the comprehensive assessment tool. MATERIALS AND METHODS:
      Sixty gynecological cancer patients were assessed for their nutritional status
      using BMI, serum albumin, hemoglobin, percentage weight lost in last 1 month, and
      scored PG-SGA. Correlation, sensitivity, specificity, and predictive values of
      the former four parameters compared to scored PG-SGA were calculated. RESULTS:
      88.33% of cases were at risk of or had some degree of malnutrition according to
      scored PG-SGA. Serum albumin level <= 2 g/dl had highest specificity and positive
      predictive value at 1, whereas percentage weight lost in last month had better
      overall sensitivity, specificity, and positive and negative predictive values of
      0.5833, 0.9444, 0.875, and 0.7727, respectively. The Pearson's correlation
      coefficient between scored PG-SGA and percentage weight lost in last 1 month was
      0.784, highest among all the parameters. CONCLUSION: 88.33% of gynecologic cancer
      cases had some degree of malnutrition or were at risk of malnutrition.
      Approximate percentage weight lost in last 1 month, that is, >= 5% may be used in
      place of the comprehensive scored PG-SGA to triage the patients in case the
      latter is not used for some reason. Severe hypoalbuminemia <= 2 g/dl is an
      indicator of severe malnutrition in gynecologic cancer cases.

PMID- 24665446
TI  - Serum zinc as a prognostic indicator in locally advanced cancer cervix patients
      receiving chemo-irradiation: A pilot study.
AB  - OBJECTIVE: To evaluate the prognostic significance of serum Zinc (S.Zn) in
      locally advanced cancer cervix (LACC) patients treated with chemo-irradiation.
      MATERIALS AND METHODS: S.Zn values in 34 females with histopathologically (HP)
      proven LACC (>/= stage II B) were prospectively measured using atomic absorption
      spectrophotometer pre- and post-treatment. Thirty-four age- and sex-matched
      healthy individuals were also evaluated for the parameter during the course of
      the study. After completion of treatment, the patients were divided into 2 groups
      based on the response, 1 - Complete response (CR) and 2 - Partial/No response
      (PR/NR). These groups were compared based on the observations of the studied
      parameter. RESULTS: The mean post-treatment S.Zn values were significantly higher
      in group 1 as compared to group 2 (P < 0.05). CONCLUSION: In our study, patients
      achieving CR had higher mean levels of S.Zn compared to patients achieving PR/NR.
      We advocate further in-depth studies to evaluate the role of S.Zn in the
      prognosis of LACC patients treated with chemo-irradiation.

PMID- 24665447
TI  - p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix
      and their correlation with human papilloma virus 16 and 18.
AB  - BACKGROUND AND OBJECTIVE: Persistent high risk human papilloma virus (HPV)
      infection is probably the best predictor of increased risk of cervical cancer,
      but expression of certain markers of cell proliferation and apoptosis have been
      studied. The present study was conducted to evaluate the expression of p53 and
      bcl2 in premalignant and malignant lesions of cervix and its correlation with HPV
      type 16 and 18. MATERIALS AND METHODS: The study comprised of 35 cases (including
      24 prospective cases and 11 retrospective cases) of premalignant and malignant
      lesions of the cervix. Slides were stained with Hematoxylin and Eosin and p53,
      bcl2 (immunohistochemistry), HPV 16 and HPV 18 (in situ hybridization). RESULTS:
      p53 positivity was seen in 8/19 (42.1%) cases of cervical intraepithelial
      neoplasia (CIN) and 8/16 (50%) cases of carcinoma cervix, the difference not
      significant statistically. The difference in bcl2 expression in CIN versus
      carcinoma cervix (84.21% vs. 43.75%) was statistically significant (P = 0.030).
      There was no significant difference between p53 and bcl2 expression and the stage
      and grade of the tumors. Seven out of 19 cases of CIN (36.84%) were positive for
      HPV 16/18 infection and 8/16 cases (50%) of carcinoma cervix were HPV positive (P
      = 0.628). CONCLUSIONS: No significant association was found between HPV 16/18
      infection and p53 and bcl2 expression in premalignant and malignant lesions of
      uterine cervix. Although, bcl2 staining showed a significant difference between
      CIN and carcinoma cervix, a larger case series is required to assess the
      association between HPV infection and overexpression of p53 and bcl2 proteins in
      these lesions.

PMID- 24665448
TI  - Study of socio-demographic determinants of esophageal cancer at a tertiary care
      teaching hospital of Western Maharashtra, India.
AB  - BACKGROUND: Esophageal cancer has a peculiar geographical distribution and shows
      marked differences in incidence within a particular geographical region.
      Presently, as there seems little prospect of early detection of this cancer, an
      understanding of the etiological factors may suggest opportunities for its
      primary prevention. OBJECTIVES: The present study was carried out to find out the
      socio-demographic determinants of esophageal cancer in a tertiary care teaching
      hospital of western Maharashtra, India. MATERIALS AND METHODS: A retrospective
      hospital record-based study was carried out for the period of five years (2007
      2011) in the department of Radiotherapy of Pravara Rural Hospital, Loni, western
      Maharashtra, India. A total of 5879 patients were diagnosed with cancer, of them,
      207 (3.52%) patients had esophageal cancer. Data was collected on the basis of
      the patients' record in the hospital and analyzed in the form of percentage and
      proportions whenever appropriate. RESULTS: Out of total 5879 patients who were
      diagnosed with cancer during the five studied years, 207 (3.52%) patients had
      esophageal cancer, of which 121 (58.46%) were males and 86 (41.54%) were females,
      which show predominance of males over females. Most of the patients (28.50%)
      belonged to lower class, while only 9.66% were from upper class. Majority of the
      patients (54.14%) had a history of tobacco chewing, followed by smoking
      (cigarette, bidi, or both) in 36.94% and alcohol in 21.65%. CONCLUSION: The
      present study shows that esophageal cancer constitutes 3.52% of cancer cases.
      There is a need to screen the high-risk group of people, improve socio-economic
      status, and efforts must be made to introduce a set of preventive measures that
      have the potential to significantly reduce the burden of disease and to help
      bridge the gap between research and public awareness.

PMID- 24665449
TI  - Eribulin drug review.
AB  - Eribulin is an anticancer drug approved for treatment of metastatic breast
      cancer. This drug is a synthetic derivative from Japanese marine sponge
      Halichondria okadai. It acts by interfering with the microtubular growth
      ultimately leading to apoptosis after prolonged mitotic blockage. In patients
      with metastatic breast cancer refractory to anthracyclines and taxanes, eribulin
      is one of the life-saving options. Neutropenia, neuropathy and QT prolongation
      are the most frequent adverse events associated with this drug. Phase I/II trials
      are also underway in refractory lung, ovarian, pancreatic, bladder, and soft
      tissue tumors. Larger prospective studies will define the role of this drug in a
      wide variety of tumors, and the future looks very promising. 

PMID- 24665450
TI  - Late effects of treatment in survivors of childhood cancer from a tertiary cancer
      center in South India.
AB  - BACKGROUND: Improved survival after childhood cancer is attributed to intensive,
      aggressive therapy, adverse sequelae of which can manifest months to years after
      completion of treatment. There is little information about the late adverse
      effects of both childhood cancer and its therapy in survivors in India. AIM: To
      determine the long-term sequelae associated with therapy in childhood cancer
      survivors attending a tertiary cancer center in India. MATERIALS AND METHODS: We
      studied 155 consecutive survivors of childhood cancer who were <=14 years at the
      time of diagnosis and had completed 3 years of follow-up. The study included a
      complete history and clinical examination, with specific investigations to detect
      organ toxicity. Quality of life (QOL) was assessed from responses to a
      standardized questionnaire. Neurocognitive assessment was carried out in 20
      survivors with an adaptation of the revised Wechsler adult intelligence scale for
      adults and the Malins intelligence scale for children. RESULTS: The late effects
      included impaired fertility in 38 patients (24.5%), impaired growth pattern in 7
      (4.5%), endocrine dysfunction in 7 (4.5%) and second malignancy in 2 (1.2%).
      Three of the 20 patients assessed had severe neurocognitive impairment. A high
      QOL was reported by 60% of survivors and an "average" QOL by 38%. CONCLUSION: Our
      study showed that most survivors had a good QOL and our results will help
      clinicians to better monitor childhood cancer survivors in countries with limited
      resources.

PMID- 24665451
TI  - Management of relapsed-refractory diffuse large B cell lymphoma.
AB  - Relapsed-Refractory Diffuse Large B Cell Lymphoma (RR DLBCL), which accounts for
      approximately one-third of patients with DLBCL, remains a major cause of
      morbidity and mortality. Managing RR DLBCL continues to be a challenge to the
      treating hemato-oncologist. Salvage high-dose chemotherapy followed by autologous
      stem cell transplantation is the standard of care for chemosensitive relapses in
      DLBCL. Various salvage regimens are available, but the quest for an optimal
      regimen continues. The addition of rituximab to the salvage regimen has improved
      the outcome of RR DLBCL. Several pertinent issues regarding the management of RR
      DLBCL are discussed in this short review. 

PMID- 24665452
TI  - Counterpoint: Angelina's choice-or the choice of anyone else in her place.

PMID- 24665453
TI  - Cancer notification in India.
AB  - In many developed countries, notification of cancer cases is compulsory.
      Developing countries including India accounts for more than half of new cancer
      cases in the world, however notification of cancer is not yet mandatory. The
      primary purpose of notification is to effect prevention and control and better
      utilization of resources. It is also a valuable source for incidence, prevalence,
      mortality and morbidity of the disease. Notification of cancer will lead to
      improved awareness of common etiologic agents, better understanding of common
      preventable causes and better utilization of health resources with better
      monitoring and evaluation of the effectiveness of health programs such as cancer
      screening and cancer treatment programs, which ultimately might improve survival.
      Notification of cancer can be done by the doctor or the hospital. Akin to the
      integrated disease surveillance project where more than 90% of the districts
      report weekly data through E-mail/portal, notification of cancer can be
      implemented if it is incorporated into the National Program for Prevention and
      Control of Cancer, Diabetes, Cardiovascular diseases and Stroke scheme. The need
      of the hour is cancer notification in India. 

PMID- 24665454
TI  - Overview of pediatric oncology and hematology in Myanmar.
AB  - Myanmar is a country in southeast Asia in political, economic and healthcare
      transition. There are currently only two pediatric oncology centers serving a
      population of almost 19 million children. An estimated 85-92% of children with
      cancer are undiagnosed or not receiving treatment. Abandonment of treatment is as
      high as 60%. Although a number of chemotherapy agents are available, difficulties
      remain concerning treatment costs, quality control and the availability of
      supportive care. Radiotherapy services are also limited and not usually included
      in pediatric protocols. Healthcare professional training, improved diagnostics,
      strategies to tackle abandonment of treatment and the development of a parents'
      support group are major priorities. Local and international partnerships
      including a recent partnership with world child cancer are essential in the
      interim to support the development of pediatric oncology and hematology in
      Myanmar. A unique opportunity exists to support the development of preventive,
      diagnostic, curative and palliative care for children's cancer in Myanmar from
      the outset. 

PMID- 24665455
TI  - Is imatinib still the best choice as first-line oral TKI.
AB  - Targeted therapy is the buzz word these days. A decade back the emergence of
      tyrosine kinase inhibitor Imatinib on the horizon, as the targeted therapy, had
      captured the imagination of everyone in the field of cancer. It is encouraging to
      see a large number of patients getting relief from deadly CML disease and leading
      a good quality of life with the help of this drug. However, sky is not the limit
      and now we have second and third generation tyrosine kinase inhibitors. I still
      remember the sagacious smile on the face of late Dr. John Goldman, when I asked
      him about his preferred choice and he replied and I quote "this is going to be
      the debate of the decade." Here I take the opportunity to contribute to this
      debate. I have scrutinized various aspects of the three TKIs, now recommended,
      for the treatment of CML. I'm still convinced it is too early to shift our
      practice completely towards 2G TKI as more time is required to make a clear
      recommendation. 

PMID- 24665456
TI  - Using 2(nd) generation tyrosine kinase inhibitors in frontline management of
      chronic phase chronic myeloid leukemia.
AB  - Choices in medicine come with responsibility. With several TKI's (Tyrosine kinase
      inhibitors) available for front-line management of CML (Chronic Myeloid
      Leukemia), an astute clinician has to personalise, rationalise and take a
      pragmatic approach towards selection of the best drug for the 'patient in
      question'. Though it is hotly debated as to which TKI will triumph, the truth of
      this debate lies in individualising treatment rather than a general 'all size
      fits all' approach with imatinib. I personally believe that the second generation
      TKI's will suit most patient clinical profiles rather than prescribing imatinib
      to all and I have strived to make a strong case for them in front line treatment
      of CML. Though Imatinib may remain the first line choice for some patients, my
      efforts in this debate are mainly geared towards breaking the myth that imatinib
      is the sole 'block buster' on the CML landscape. 

PMID- 24665457
TI  - Chronic myeloid leukemia: When the going gets tough.

PMID- 24665458
TI  - HPV vaccination in India.

PMID- 24665459
TI  - Authors' reply.

PMID- 24665460
TI  - Radiotherapy planning for breast cancer.

PMID- 24665461
TI  - Changes of skin collagen orientation associated with chronological aging as
      probed by polarized-FTIR micro-imaging.
AB  - During chronological skin aging, alterations in dermal structural proteins cause
      morphological modifications. Modifications are probably due to collagen fiber
      (type I collagen) rearrangement and reorientation with aging that have not been
      researched until now. FTIR microspectroscopy appears as an interesting method to
      study protein structure under normal and pathological conditions. Associated with
      a polarizer, this vibrational technique permits us to probe collagen orientation
      within skin tissue sections, by computing the ratio of integrated intensities of
      amide I and amide II bands. In this study, we used the polarized-FTIR imaging to
      evaluate molecular modifications of dermal collagen during chronological aging.
      The data processing of polarized infrared data revealed that type I collagen
      fibers become parallel to the skin surface in aged skin dermis. Our approach
      could find innovative applications in dermatology as well as in cosmetics. 

PMID- 24665462
TI  - The application of non-linear curve fitting routines to the analysis of mid
      infrared images obtained from single polymeric microparticles.
AB  - For the first time, we report a series of time resolved images of a single PLGA
      microparticle undergoing hydrolysis at 70  degrees C that have been obtained
      using attenuated total reflectance-Fourier transform infrared spectroscopic (ATR
      FTIR) imaging. A novel partially supervised non-linear curve fitting (NLCF) tool
      was developed to identify and fit peaks to the infrared spectrum obtained from
      each pixel within the 64 * 64 array. The output from the NLCF was evaluated by
      comparison with a traditional peak height (PH) data analysis approach and
      multivariate curve resolution alternating least squares (MCR-ALS) analysis for
      the same images, in order to understand the limitations and advantages of the
      NLCF methodology. The NLCF method was shown to facilitate consistent spatial
      resolution enhancement as defined using the step-edge approach on dry
      microparticle images when compared to images derived from both PH measurements
      and MCR-ALS. The NLCF method was shown to improve both the S/N and sharpness of
      images obtained during an evolving experiment, providing a better insight into
      the magnitude of hydration layers and particle dimension changes during
      hydrolysis. The NLCF approach facilitated the calculation of hydrolysis rate
      constants for both the glycolic (kG) and lactic (kL) acid segments of the PLGA
      copolymer. This represents a real advantage over MCR-ALS which could not
      distinguish between the two segments due to colinearity within the data. The NLCF
      approach made it possible to calculate the hydrolysis rate constants from a
      single pixel, unlike the peak height data analysis approach which suffered from
      poor S/N at each pixel. These findings show the potential value of applying NLCF
      to the study of real-time chemical processes at the micron scale, assisting in
      the understanding of the mechanisms of chemical processes that occur within
      microparticles and enhancing the value of the mid-IR ATR analysis. 

PMID- 24665463
TI  - Macroscopic Fourier transform infrared scanning in reflection mode (MA-rFTIR), a
      new tool for chemical imaging of cultural heritage artefacts in the mid-infrared
      range.
AB  - In this paper we demonstrate that by means of scanning reflection FTIR
      spectroscopy, it is possible to record highly specific distribution maps of
      organic and inorganic compounds from flat, macroscopic objects with cultural
      heritage value in a non-invasive manner. Our previous work involved the recording
      of macroscopic distributions of chemical elements or crystal phases from painted
      works of art based on respectively macroscopic X-ray fluorescence or X-ray powder
      diffraction analysis. The use of infrared radiation instead of X-rays has the
      advantage that more specific information about the nature and distribution of the
      chemical compounds present can be gathered. This higher imaging specificity
      represents a clear advantage for the characterization of painting and artist
      materials. It allows the distribution of metallo-organic compounds to be
      visualized and permits distinguishing between pigmented materials containing the
      same key metal. The prototype instrument allows the recording of hyperspectral
      datacubes by scanning the surface of the artefact in a contactless and sequential
      single-point measuring mode, while recording the spectrum of reflected infrared
      radiation. After the acquisition, spectral line intensities of individual bands
      and chemical distribution maps can be extracted from the datacube to identify the
      compounds present and/or to highlight their spatial distribution. Not only is
      information gained on the surface of the investigated artefacts, but also images
      of overpainted paint layers and, if present, the underdrawing may be revealed in
      this manner. A current major limitation is the long scanning times required to
      record these maps. 

PMID- 24665464
TI  - Compound identification in GC-MS by simultaneously evaluating the mass spectrum
      and retention index.
AB  - We report a compound identification method (SimMR), which simultaneously
      evaluates the mass spectrum similarity and the retention index distance using an
      empirical mixture score function, for the analysis of GC-MS data. The performance
      of the developed SimMR method was compared to that of two existing compound
      identification strategies. One is the mass spectrum matching method without
      incorporation of retention index information (SM). The other is the method that
      sequentially evaluates the mass spectrum similarity and retention index distance
      (SeqMR). For comparison purposes, we used the NIST/EPA/NIH Mass Spectral Library
      2005. Our study demonstrates that SimMR performs the best among the three
      compound identification methods, by improving the overall identification accuracy
      up to 1.53% and 4.81% compared to SeqMR and SM, respectively. 

PMID- 24665466
TI  - Alternating polymer micelle nanospheres for optical sensing.
AB  - A novel concept of nanosized fluorimetric sensors is proposed, using alternating
      polymers as self assembling micelles that can be crosslinked resulting in stable
      polymeric nanoparticles. The thus obtained nanospheres have sizes close to 250 nm
      or 130 nm, depending on the preparation procedure and the negative surface
      charge, due to the presence of carboxyl groups on the surface. By a simple
      procedure, the nanospheres can be effectively loaded with compounds of choice,
      e.g. ionophores and ion-exchangers previously used to induce ionic sensitivity in
      polyacrylate or poly(vinyl chloride) micro- and nanospheres (miniature optrodes),
      thus allowing for optical or fluorimetric quantification of analytes. As a proof
      of concept, H(+) sensitive colorimetric and fluorimetric sensors and K(+)
      fluorimetric sensors using classical optrode approach were prepared and tested.
      The obtained sensors were characterized by high sensitivity, fast and reversible
      responses. Both K(+) and H(+) sensors were characterized by a broad response
      range resulting from the significant effect of processes occurring on the surface
      of the nanospheres. Due to this effect, the fluorimetric responses of the
      obtained spheres are significantly different from those typically observed for
      miniature optrode systems, and were linear within a range of at least 5
      logarithmic units of analyte concentration. As shown, the surface groups of the
      herein proposed nanospheres can be used for the covalent linking of fluorophores
      that can be used as markers (if applied alone) or as reference dyes for
      fluorescent ion-sensitive nanospheres. 

PMID- 24665465
TI  - A novel strategy for real-time and in situ detection of cytochrome c and caspase
      9 in Hela cells during apoptosis.
AB  - Cytochrome c (cyt c) and caspase-9 were critical biomarkers in mitochondria
      mediated apoptosis. A novel electrochemical immunosensor was developed for in
      situ analysis of cyt c and caspase-9 in the cytosol. Gold nanoparticle
      polydopamine (AuNP/PDA) composites were used to fabricate the interface of the
      sensor. The anti-cyt c or anti-caspase-9 functionalized-immunosensor provided a
      biomimetic interface for immunosensing of cyt c or caspase-9 in Hela cells during
      apoptosis. The changes in the expression level of cyt c and caspase-9 in the
      cytosol upon curcumin-induced apoptosis were detected by using the proposed
      method, and also the influence of different concentrations and incubation times
      of curcumin-induced Hela cells was investigated. This method achieved a linear
      range (0.1-100 MUM) for standard cyt c and caspase-9, with a detection limit of
      0.03 +/- 0.01 MUM for standard cyt c and 0.08 +/- 0.02 MUM for standard caspase
      9. Moreover, this method was used to detect cells which could detect as low as
      100 cells which expressed cyt c and caspase-9, and also the results are in good
      agreement with standard flow cytometry analysis. The developed electrochemical
      immunosensor offered a simple and rapid approach for sensitive evaluation of
      apoptosis markers with considerable specificity and reproducibility, and also the
      developed strategy could be of great importance in clinical diagnosis and
      therapeutic research. 

PMID- 24665467
TI  - Response.

PMID- 24665468
TI  - Response.

PMID- 24665469
TI  - Reply to Coffino et al.: slippery substrates impair ATP-dependent protease
      function by slowing unfolding.

PMID- 24665470
TI  - How important was the Pill to women's economic well-being? If Roe v. Wade were
      overturned, how might society change?

PMID- 24665471
TI  - Recent evidence on the broad benefits of reproductive health policy.

PMID- 24665472
TI  - If only policy analysis were so easy.

PMID- 24665473
TI  - Further evidence on the internal validity of the early legal access research
      design.

PMID- 24665474
TI  - Breaking the cycle: drought and hunger in Kenya.

PMID- 24665475
TI  - Aesthetic deprivation in clinical settings.

PMID- 24665476
TI  - Creating your own virtual patient with CircAdapt Simulator.

PMID- 24665477
TI  - Changing times in cardiology II: interview with Prof. Panos Vardas, president of
      the European Society of Cardiology.

PMID- 24665478
TI  - [Bulk-fill-composites. Modern application technique of direct composites for
      posterior teeth].
AB  - Direct composite restorations in the posterior dentition have become an
      indispensable element of modern dentistry. The performance of these restoration,
      even in the masticatory load-bearing posterior region, has been conclusively
      proven in many clinical studies. This procedure is usually carreid out in an
      elaborate layering technique. This time-consuming procedure requires an
      economically sensible fee, corresponding to the effort involved. Aside from the
      possibilies that highly aesthetic composites offer in the application of
      polychromatic multiple-layer techniques, there is also a great market demand for
      the most simple and quick and therefore economical composite-based materials for
      posterior teeth. These products are offered in the category of bulk-fill
      composite.

PMID- 24665479
TI  - [Pediatric ophthalmology].

PMID- 24665481
TI  - Drug therapy for older adults.

PMID- 24665480
TI  - A multivariate calibration procedure for UV/VIS spectrometric monitoring of BHK
      21 cell metabolism and growth.
AB  - Monitoring mammalian cell culture with UV-vis spectroscopy has not been widely
      explored. The aim of this work was to calibrate Partial Least Squares (PLS)
      models from off-line UV-vis spectral data in order to predict some nutrients and
      metabolites, as well as viable cell concentrations for mammalian cell bioprocess
      using phenol red in culture medium. The BHK-21 cell line was used as a mammalian
      cell model. Spectra of samples taken from batches performed at different
      dissolved oxygen concentrations (10, 30, 50, and 70% air saturation), in two
      bioreactor configurations and with two strategies to control pH were used to
      calibrate and validate PLS models. Glutamine, glutamate, glucose, and lactate
      concentrations were suitably predicted by means of this strategy. Especially for
      glutamine and glucose concentrations, the prediction error averages were lower
      than 0.5060.10 mM and 2.2160.16 mM, respectively. These values are comparable
      with those previously reported using near infrared and Raman spectroscopy in
      conjunction with PLS. However, viable cell concentration models need to be
      improved. The present work allows for UV-vis at-line sensor development, decrease
      cost related to nutrients and metabolite quantifications and establishment of fed
      batch feeding schemes.

PMID- 24665482
TI  - In the spotlight: Rising stars in long term and post-acute care.

PMID- 24665483
TI  - Match making.

PMID- 24665484
TI  - In reply.

PMID- 24665485
TI  - [Care demand strenuousness model 1.0: to a model of random care allocation?].

PMID- 24665486
TI  - Insurers, behave yourselves: TMA pushes national code of conduct.

PMID- 24665487
TI  - [Increased ventral striatal CB1 receptor binding is related to negative symptoms
      in drug-free patients with schizophrenia].

PMID- 24665488
TI  - [Depression accelerates physical aging].

PMID- 24665489
TI  - [Cognitive remediation therapy in patients with a severe or enduring eating
      disorder].

PMID- 24665491
TI  - TMA practice consulting will change you for the better.

PMID- 24665492
TI  - Author's reply: To PMID 24379662.

PMID- 24665493
TI  - [Reply to Cense].

PMID- 24665494
TI  - [Reply to Schulte].

PMID- 24665495
TI  - [Retraction: Usefulness of micronutrients in the treatment of periodontitis].

PMID- 24665496
TI  - House of Delegates inaugural address.

PMID- 24665497
TI  - Caught in the middle of change.

PMID- 24665498
TI  - A conversation with MAG member and Georgia Rep. Ben Watson, M.D.

PMID- 24665499
TI  - A first-hand look at serving as MAG's "Doctor of the Day" at the Capitol.

PMID- 24665500
TI  - Criticizing your colleague in front of patients.

PMID- 24665501
TI  - Restrictive covenants: points to ponder.

PMID- 24665502
TI  - A legal primer on restrictive covenants.

PMID- 24665503
TI  - When cardiologists have chest pain.

PMID- 24665504
TI  - Some musings on business associate agreements.

PMID- 24665505
TI  - The medical staff and fraud?

PMID- 24665506
TI  - New Georgia Medicaid requirements for OPR physicians.

PMID- 24665507
TI  - Unusual circumstances stump a timely myocardial infarction diagnosis.

PMID- 24665508
TI  - Barium on.

PMID- 24665510
TI  - Couples counselling and marriage services provide huge benefits, new report
      reveals.

PMID- 24665509
TI  - The wonders of medical science.

PMID- 24665511
TI  - QNI fund for innovation and leadership 2014 projects announced.

PMID- 24665512
TI  - Parenting programmes can improve life chances of children with behavioural
      problems, new research reveals.

PMID- 24665513
TI  - Alert card launched to help young people with dyspraxia in difficult situations.

PMID- 24665514
TI  - 'Toxic climate' causing increasing mental health issues for young people.

PMID- 24665515
TI  - Scotland: the mental health of a nation examined.

PMID- 24665516
TI  - The cutting season.

PMID- 24665517
TI  - The differences between lactose intolerance and cow's milk protein allergy.

PMID- 24665518
TI  - Skin infections in children.

PMID- 24665519
TI  - Are babies' lives at risk?

PMID- 24665520
TI  - The big challenge.

PMID- 24665521
TI  - The study of dental history: Raison D'etre.

PMID- 24665522
TI  - Dental surgery in ancient Egypt.
AB  - Many different surgical procedures have over the years been attributed to the
      ancient Egyptians. This is also true regarding the field of dental surgery. The
      existence of dentists in ancient Egypt is documented and several recipes exist
      concerning dental conditions. However, no indications of dental surgery are found
      in the medical papyri or in the visual arts. Regarding the osteological
      material/mummies, the possible indications of dental surgery are few and weak.
      There is not a single example of a clear tooth extraction, nor of a filling or of
      an artificial tooth. The suggested examples of evacuation of apical abscesses can
      be more readily explained as outflow sinuses. Regarding the suggested bridges,
      these are constituted of one find likely dating to the Old Kingdom, and one
      possibly, but perhaps more likely, dating to the Ptolemaic era. Both seem to be
      too weak to have served any possible practical purpose in a living patient, and
      the most likely explanation would be to consider them as a restoration performed
      during the mummification process. Thus, while a form of dentistry did certainly
      exist in ancient Egypt, there is today no evidence of dental surgery.

PMID- 24665523
TI  - How the insightful leadership of James English transformed a traditional dental
      school into a leading educational institution.
AB  - During the 1960s, the dental school at the University of Buffalo underwent a
      profound change, as a result of its merger with the State University of New York
      (SUNY), and, very importantly, because of the outstanding leadership provided by
      Dean James A. English. This article contrasts what the school was like in 1960
      before Dean English's arrival, and what it had become in 1970 when his deanship
      ended. It also recounts the leadership qualities of Dean English and the measures
      he took to transform the dental school into a leading educational institution.
      During his tenure, the school experienced profound change, including integration
      of medicine with dentistry in the curriculum; "internationalization" of dental
      education and research; organization of the first Oral Biology Department and PhD
      graduate program in a dental school in the United States; insistence on
      "knowledge-driven" dental practice--a concept we now term "evidenced-based
      dentistry"; the establishment of novel approaches to dental education including
      the "diagonal" curriculum; incorporation of prevention in practice; elective
      courses for dental students; and comprehensive clinical care. All of these
      accomplishments were novel for the day and greatly influenced incorporation of
      similar innovations in many schools around the world.

PMID- 24665524
TI  - Twentieth century influences on Queensland dental practice: a tangential view.
AB  - Political scientists, historians and journalists intermittently suggest that,
      within the Australian context, public policy and its administration in Queensland
      are different. Significant evidence suggests that, from colonial times, distance
      and decentralization have influenced Queenslanders' demographic profiles and
      collective identity. Using historical analysis to qualify and quantify both the
      alleged difference and its social significance warrants caution. Nonetheless,
      some developments in public dental policy and the practice of dentistry across
      Queensland provide intriguing contrasts. This study, a literature review, uses
      historical method. The authors focus on pivotal proceedings that affected both
      the dental profession and dental practice in the twentieth century. These events
      embraced the genesis and evolution of dental education and influenced fluoride
      politics and policies controlling the delivery of public dental services. These
      developments reflected not only the contemporaneous social and political fabric
      but also the broader influences on Queensland history, namely: area, distance,
      decentralization, groundwater, isolation and topography. The events and
      observations in this report lend some support to hypotheses concerning a
      Queensland difference within the Australian context of public policy and its
      administration.

PMID- 24665525
TI  - Dental postcards LIV. An early female dentist practices oral surgery.

PMID- 24665526
TI  - Dental trade cards XXXIX. Josiah A Pearson, Baton, Vermont.

PMID- 24665527
TI  - [Reality show in the hospital? County councils should think twice].

PMID- 24665528
TI  - [The future increase in the number of sick elderly. Take care of life!].

PMID- 24665529
TI  - [Self-injurious behavior is common and stigmatizing. National self-injury project
      working for better treatment and care].

PMID- 24665530
TI  - [Strengthened role for statins in primary prevention of cardiovascular disease].

PMID- 24665531
TI  - [Treatment of non-suicidal self-injurious behavior requires a clear structure.
      Randomized controlled trials show evidence for dialectical behavior therapy and
      mentalization-based treatment].

PMID- 24665532
TI  - [High percentage approved intern reports in the R & D program VESTA. Evaluation
      of general practice program for the compulsory project work].

PMID- 24665533
TI  - [Increased nursing care needs primary cause of long hospital stay in medical
      clinics. A retrospective medical record study proves that early care planning
      could provide better hospital bed capacity].

PMID- 24665534
TI  - [WHO initiatives to increase access to surgery in resource-poor areas].

PMID- 24665535
TI  - [Our shared venereological future--broadened horizons and sensible choices].

PMID- 24665536
TI  - [One in three interns have felt discriminated].

PMID- 24665537
TI  - [The advocate Magnus Hirschfeld and Swedish physicians' view of homosexuality].

PMID- 24665538
TI  - A milestone.

PMID- 24665539
TI  - Reasons to be cheerful.

PMID- 24665540
TI  - Audit of the health service executive orthodontic referral pathway between 2009
      and 2011.

PMID- 24665541
TI  - Response from the author.

PMID- 24665542
TI  - Radio campaign reaches huge number of listeners, promotes dental visits.

PMID- 24665543
TI  - Most Irish adults believe their teeth and gums are healthy, says survey.

PMID- 24665544
TI  - IDA makes its case on infection control to Dental Council.

PMID- 24665545
TI  - Sixty volumes of the Journal.

PMID- 24665546
TI  - Intracranial abscess secondary to dental infection.
AB  - We report a case of Aggregatibacter actinomycetemcomitans (A.
      actinomycetemcomitans) bacteraemia and secondary brain abscess in a patient where
      periodontal disease was implicated as the probable source.

PMID- 24665547
TI  - Motivational interviewing for dental clinicians.
AB  - Motivational interviewing (MI) is a patient-centred, directive, therapeutic
      approach that supports patients' readiness to change by exploring their
      ambivalence about doing so. This increases the patients' motivation and helps
      them to commit to the process of change. In relation to dentistry, MI has been
      effectively used to: promote oral health behaviour; facilitate smoking cessation;
      and, alter health behaviours.

PMID- 24665548
TI  - Midazolam and drug-drug interactions in dental conscious sedation.
AB  - Careful prescribing is paramount in clinical practice. Potential drug-drug
      interactions need to be considered. Midazolam is the drug of choice for the
      purpose of IV sedation. To ensure safe clinical practice, the patient's current
      medications need to be recorded. CLINICAL RELEVANCE: An update on the drug
      interactions relating to midazolam are worthy of scrutiny as its use becomes more
      commonplace in clinical practice. OBJECTIVE: The dentist should understand the
      possible implications for drug interactions when sedating patients using
      midazolam.

PMID- 24665549
TI  - Stressed?

PMID- 24665550
TI  - A new vision of care. A smarter patient room. Design team creates a view into the
      future.

PMID- 24665551
TI  - Moving ahead. Executives assess facilities in light of Obamacare.

PMID- 24665552
TI  - Safe signals. Managing clinical alarm systems for optimal performance.

PMID- 24665553
TI  - Designing hospital office environments to foster teamwork.

PMID- 24665554
TI  - Plumbing protection. Latest fixtures for hospitals support water conservation,
      sustainability and cleaning ease--all while providing a more homelike feel.

PMID- 24665555
TI  - Partnering between ES and facilities teams.

PMID- 24665556
TI  - Common cause. Health care makes strides toward unified building codes.

PMID- 24665557
TI  - Lifting the sheets. Preventing and managing health care bed bug problems.

PMID- 24665558
TI  - The power of 3... Increasing member value and strengthening organized dentistry.

PMID- 24665559
TI  - Patient's page. Water fluoride.

PMID- 24665560
TI  - Introducing the ODA Insurance Exchange.

PMID- 24665561
TI  - Dr Tamara Berg changes lives through the Smiles for Sucess Foundation.

PMID- 24665562
TI  - New dentist spotlight: Dr. Matt Gray.

PMID- 24665563
TI  - Updates on the Affordable Care Act.

PMID- 24665564
TI  - Trusted profession-trusted professional nurses.

PMID- 24665565
TI  - Outgoing interim executive director.

PMID- 24665566
TI  - Nursing Peer Health Assistance Program: ten things nurses need to know.

PMID- 24665567
TI  - Colorado nurses embrace the practice of substance use screening and intervention.

PMID- 24665568
TI  - Meet a real "Call the Midwife".

PMID- 24665569
TI  - Nosocomial infections in the Intesive Care Unit, Univerisity Hospital for
      Infectious and Tropical Diseases, Belgrade, Serbia.
AB  - BACKGROUND/AIM: Nosocomial infections (NIs) are an important cause of morbidity,
      mortality and prolonged hospitalizations. Fifty percent of NIs have been reported
      in Intensive Care Units. The aim of this study was to determine the frequency and
      type of NIs among critically ill patients treated in the University Hospital for
      Infectious and Tropical Diseases, Clinical Centre of Serbia, as well as risk
      factors for acquiring them. METHODS: This prospective cohort study included 52
      patients treated in the Intensive Care Unit from January to June 2004. The
      diagnosis of NI was established according to the Centers for Disease Control and
      Prevention (CDC) definition, based on clinical presentation, radiological and
      microbiological findings, etc. Statistical data processing was done by using the
      electronic data base organized in SPSS for Windows version 10.0. The level of
      statistical significance was defined as p < 0.05. RESULTS: NIs were found in 33
      (63.4%) of 52 inpatients. Urinary tract infections (UTIs), pneumonia, and soft
      tissue infections, the most common nosocomial infections in our setting, were
      recorded in 41.0%, 25.6%, and 23.1%, of patients, respectively. Several factors
      contributed to a high incidence of these infections: chronic comorbidities (p <
      0.01), the presence of indwelling devices such as urinary tract catheters (p <
      0.01), endotracheal tubes (p < 0.05) along with mechanical ventilation (p <
      0.05). CONCLUSION: The majority of patients with NIs had chronic underlying
      comorbidities. All the patients with UTIs had urinary catheters. The most
      important risk factors for the development of nosocomial pneumonias were
      endotracheal intubation and mechanical ventilation. The patients with pneumonia
      had the highest mortality.

PMID- 24665570
TI  - Economic burden of cardiovascular diseases in Serbia.
AB  - BACKGROUND/AIM: Cardiovascular disease imposes a burden to society in terms of
      mortality, morbidity and economic losses. The aim of this study was to estimate
      the economic burden of cardiovascular disease in Serbia in 2009 from the
      perspective of the society. METHODS: For the purpose of the study cardiovascular
      disease was defined by the International Classification of Diseases, 10th
      revision, as the following diagnosis: hypertension, coronary heart disease,
      cardiomyopathy, heart failure and cerebrovascular disease. The prevalence, top
      down method was used to quantify the annual cardiovascular costs. Productivity
      losses were estimated using the human capital approach and the friction cost
      method. A discount rate of 5% was used to convert all future lifetime earnings
      into the present value. RESULTS: The total direct costs of cardiovascular disease
      in 2009 were Euro 400 million. The results showed that more than half a million
      working days were lost due to incapacity resulting from cardiovascular diseases,
      yielding the Euro 113.9 millon. The majority of total costs (Euro 514.3 million)
      were for: medication (29.94%), hospital days (28.97%) and hospital inpatient care
      -surgical and diagnostic interventions (17.84%). The results were robust to a
      change in 20% of volume or the unit price of all direct and indirect cost and to
      discount rate 2% and 10%. CONCLUSIONS; The total cardiovascular disease costs in
      2009 represented approximately 1.8% of the Serbian gross domestic product. The
      results of the study would be valuable to health policy makers to bridge the gap
      between invested resources and needs, in order to improve cardiovascular disease
      outcomes.

PMID- 24665571
TI  - Cost-effectiveness analysis of tocilizumab in combination with methotrexate for
      rheumatoid arthritis: a Markov model based on data from Serbia, country in
      socioeconomic transition.
AB  - BACKGROUND/AIM: Recent studies have shown that biological treatments for
      rheumatoid arthritis can change the course of rheumatoid arthritis and improve
      functional ability of patients with rheumatoid arthritis. In spite of this fact,
      use of biological therapy is still limited by high prices of these medicines,
      especially in countries in socioeconomic transition. The aim of our study was to
      compare cost-effectiveness of a combination of tocilizumab and methotrexate with
      methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic
      transition. METHODS: For the purpose of our study we designed a Markov model
      using data on therapy efficacy from the available literature, and data on the
      costs of health states calculated from records of actual patients treated in the
      Clinical Center Kragujevac, Serbia. The duration of one cycle in our model was
      set at one month, and the time horizon was 480 months (40 years). The study was
      done from the social perspective, and all the costs and outcomes were discounted
      for 3% per year. RESULTS: Treating rheumatoid arthritis with disease-modifying
      antirheumatic drugs (DMARDs) alone was more cost-effective in comparison with a
      combination of biologic treatment with tocilizumab and DMARDs. The total costs
      for treating a patient with DMARDs for one year were on average 261,945.42 RSD,
      or 2,497.70 Euro and the total costs for treatment with tocilizimab plus DMARDs
      were on average 1,959,217.44 RSD, or 18,659.20 Euro. However, these results are
      susceptible to changes in costs and treatment effects of tocilizumab in patients
      with more severe forms of rheumatoid arthritis. CONCLUSION: Our results show that
      the use of tocilizumab for rheumatoid arthrits in economic environment of Serbia
      is not cost-effective. Use of tocilizumab for treating rheumatoid arthritis can
      become affordable, if costs of its use become lower. In order to start using
      expensive biologic medicines in patients in transitional countries, special
      strategy and pricing policy of international pharmaceutical companies are
      necessary, which would include calculation of prices of biologic medicines on the
      basis of local pharmacoeconomic studies.

PMID- 24665572
TI  - The role of biochemical markers as early indicators of cardiac damage and
      prognostic parameters of perinatal asphyxia.
AB  - BACKGROUND/AIM: In recent years, the focus of interest of the scientific
      community is the application of heart markers as early indicators and prognostic
      parameters of perinatal asphyxia (PA). The aim of this study was to evaluate the
      significance of clinical application of heart markers in term newborns with
      perinatal asphyxia. METHODS: During a 3-year period we analyzed 91 full-term
      newborns (55 with and 36 without perinatal asphyxia). In all the subjects within
      the first 24-48 h after birth, we simultaneously determined serum concentrations
      of cardiac troponin I, brain natriuretic peptide, MB fraction of creatine kinase
      (CK-MB) and C-reactive protein. RESULTS: In the group of full-term neonates with
      PA significantly higher levels of cardiac tropon-inI (p = 0.000), CK-MB fraction
      (p = 0.000), brain natriuretic peptide (p = 0.003) and C-reactive protein (p =
      0.017) were found, compared to the group of healthy full-term newborns. In merged
      group (n = 91) cardiac troponin I level correlated with the fifth minute Apgar
      score (r = -0.637, p = 0.000) and the serum lactate concentration in the first
      12h after birth (r = 0.529, p = 0.000). Early increase in cardiac troponin I >
      0.135 microg/L predicted the risk of death with the sensitivity of 84.6% and
      specificity of 85.9%, while the increase in CK-MB fraction, brain natriuretic
      peptide and C-reactive protein did not have a predictive value with respect to a
      mortality outcome. CONCLUSION: Among the tested cardiac markers, cardiac troponin
      I is the most sensitive and the only reliable early predictor of mortality in
      full-term neonates with perinatal asphyxia.

PMID- 24665573
TI  - Clinical features of endobronchial tuberculosis.
AB  - BACKGROUND/AIM: Endobronchial tuberculosis (EBTB) is a specific type of pulmonary
      tuberculosis which often affect the tracheobronchial tree, and can be
      microbiologically and/or pathohistologically confirmed. The aim of the study was
      to determine the clinical features and diagnostic aspects of EBTB. METHODS: This
      retrospective study was conducted at the Clinic for Lung Diseases, Clinical
      Center of Serbia, Belgrade, from January 1997 to December 2007. All patients with
      EBTB confirmed by bronchoscopy with biopsy during a study period were analysed.
      Data included the patient's medical history, a physical exam, chest X-ray,
      mycobacterial analysis of sputum samples, endoscopic types and patohistological
      confirmation. RESULTS: In the study, 57.6% of the patients were males. The most
      frequent symptoms were cough (71.2%), malaise (54.20%), fever (49.2%), weight
      loss (40.7%), and hemoptysis (13.60%). Most of the patients were diagnosed within
      30 days of symptoms onset. Sputum examination showed acid-fast bacilli in 31.4%
      of the patients, while sputum culture for tuberculosis bacilli were positive in
      55.9% of the patients. The most common radiographic localization was in the upper
      lung lobes (63.5%). Cavities were present in 60.4% of the patients. The most
      common endoscopic subtype determined by bronchoscopy were nonspecific bronchitis
      (39.9%) and edematous-hyperemic subtype (36.4%). CONCLUSION: EBTB was more
      frequent among men, and among people in their fifties in our country. Detailed
      bronchoscopic examination, correlated with clinical and laboratory findings, will
      improve diagnostic rate and provide timely therapy.

PMID- 24665574
TI  - Blunt chest trauma--an audit of injuries diagnosed by the MDCT examination.
AB  - BACKGROUND/AIM: Multidetector computed tomography (MDCT) characterised by speed
      and precision is increasingly accessible in emergency wards. The aim of our study
      was to determine the most common injuries to the chest region, as well as type
      associated extrathoracic injuries, and the treatment outcome. METHODS: This
      prospective study included 61 patients with blunt trauma who were submitted to
      computed tomography (CT) of the thorax. The number of injuries was evaluated by
      organs and organ systems of the chest. The cause of the injury, the length and
      the outcome of the treatment, and the presence of injuries in other regions were
      assessed. RESULTS: Chest injuries were associated with injuries to other regions
      in 80.3% cases, predominantly injuries to extremities or pelvic bones in 54.1%
      cases, followed by head injuries in 39.3% patients. Associated thoracic injuries
      were present in 90.9% of patients with lethal outcome. Lung parenchymal lesions,
      pleural effusions and rib fractures were the most common injuries affecting
      77.1%, 65.6% and 63.9% of the cases, respectively. CONCLUSION: Blunt chest trauma
      is a significant problem affecting predominantly males in their forties and it is
      usually caused by a motor vehicle accident. In case of pneumomediastinum or
      mediastinal haematoma, the use of 3D reconstructions is advised for diagnosing
      possible tracheobronchial ruptures and thoracic aorta injuries. Increased
      resolution of CT scanners yielded a large number of findings that are occult on
      radiography, especially in the event of lung parenchymal and pleural injuries.
      However, none imaging modality can replace surgical judgement.

PMID- 24665576
TI  - Transference patterns and working alliance during the early phase of
      psychodynamic psychotherapy.
AB  - BACKGROUND/AIM: Working alliance, as a collaborative part of the therapeutic
      relationship has been proven to be one of the most powerful therapeutic factors
      in psychotherapy in general, regardless many technical differences between
      numerous psychotherapeutic modalities. On the other hand, transference is the
      basic concept of psychodynamic psychotherapy, and, according to the
      psychoanalytic theory and practice, it forms a major part of the therapeutic
      relationship. The aim of our paper was to determine the differences between the
      groups of patients with low, middle, and high working alliance scores and the
      dropout group in transference patterns, sociodemographic and clinical parameters,
      during the early phase of psychodynamic psychotherapy. METHODS: Our sample
      consisted of 61 non-psychotic patients, randomly selected by the method of
      consecutive admissions and treated with psychoanalytic psychotherapy in the
      outpatient clinical setting. The patients were prospectively followed during 5
      initial sessions of the therapeutic process. The working alliance inventory and
      Core conflictual relationship theme method were used for the estimation of
      working alliance and transference patterns, respectively. According to the
      Working Alliance Inventory scores, four groups of patients were formed and than
      compared. RESULTS: Our results show a significant difference between the groups
      of patients with low, middle, and high working alliance inventory scores and the
      dropout group on the variable--transference patterns in the therapeutic
      relationship. CONCLUSION: Disharmonious transference patterns are more frequent
      in patients who form poor quality working alliance in the early phase of
      psychotherapy, or early dropout psychotherapy. It is of great importance to
      recognize transference patterns of a patient at the beginning of the
      psychotherapeutic process, because of their potentially harmful influence on the
      quality of working alliance.

PMID- 24665575
TI  - Assessment of health status and quality of life of homeless persons in Belgrade,
      Serbia.
AB  - BACKGROUND/AIM: Homelessness is a problem with social, medical, economic,
      political and other implications. Despite a large number of studies, reports
      about health-related quality of life (HRQoL) of homeless persons remain sparse.
      There is a summary of consistent evidence that homeless people have higher
      prevalence of chronic disease (mental and somatic) than general population. The
      aim of this study was to assess HRQoL and depression in homeless persons in
      Belgrade, to describe their sociodemographic factors and health status (the
      presence of chronic mental and somatic diseases and addiction disorders) and
      analyse impact of sociodemographic factors and health status to HRQoL and
      depression of homeless persons. METHODS: The study was conducted in the Shelter
      for Adult and Elderly Persons in Belgrade, from January 1 to January 31, 2012. A
      set of questionnaires used in survey included Serbian translation of SF-36
      questionnaire, Serbian translation of Beck Depression Inventory-II (BDI-II) and
      sociodemographic questionnaire. Statistical analysis was performed by descriptive
      and analytic methods. RESULTS: Our study sample consisted of 104 adult
      participants. The majority of them were male (74%) and the mean age in the sample
      was 48.2 +/- 13.0 years. We have found that 35.6% participants had lifetime
      diagnosis of psychiatric disorder, most frequently depression (lifetime
      prevalence of 15.4% in the study group). The history of suicide attempts was
      registered in 28 (26.9%) participants. Lifetime illicit drugs use was reported by
      12.5%, daily smoking by 82.7% and daily alcohol consumption by 8.7% of the
      participants. Most common somatic chronic diseases were cardiovascular while
      chronic lung diseases were the second most frequent. Single chronic disaese was
      present in 33 (31.7%) of the participants and comorbidity of 2 chronic diseases
      was present in 20 of them. A statistically significant difference between
      participants HRQoL SF-36 domain scores and norms of general population was found
      only for role physical domain (lower in homeless, p < 0.001). ANOVA showed no
      statistically significant difference in SF-36 HRQoL domain and composite scores
      between different age groups, nor did marital status, education level, length of
      homelessness, alcohol use or smoking significantly affect the HRQoL. The mean BDI
      II score in the studied population was 19.1 +/- 11.6. Severe depression was
      registered in 20.2% of the participants, moderate in 23.1%, mild in 19.2% and
      minimal in 37.5%. A highly significant negative correlation was verified between
      BDI-II and all domains and composite scores of SF-36 (p < 0.001). CONCLUSION:
      Measures for prevention of homelessness should include: foundation of national
      registry of homeless persons, development of systemic multisectorial cooperation
      and special psychosocial intervention strategies. In homeless population, health
      care measures should be focused on prevention and treatment of mental health
      disorders and chronic somatic diseases.

PMID- 24665577
TI  - Bleeding gastroduodenal ulcers in patients without Helicobacter pylori infection
      and without exposure to non-steroidal anti-inflammatory drugs.
AB  - BACKGROUND/AIM: A high risk of bleeding in Helicobacter pylori (H. pylori)
      negative, non-steroidal anti-inflammatory drugs (NSAID)-negative ulcers
      highlights the clinical importance of analysis of the changing trends of peptic
      ulcer disease. The aim of the study was to investigate the risk factors for ulcer
      bleeding in patients with non-H. pylori infection, and with no NSAIDs use.
      METHODS: A prospective study included patients with endoscopically diagnosed
      ulcer disease. The patients were without H. pylori infection (verified by
      pathohistology and serology) and without exposure to NSAIDs and proton pump
      inhibitors (PPI) within 4 weeks before endoscopy. After endoscopy the patients
      were divided into 2 groups: the study group of 48 patients with bleeding ulcer
      and the control group of 47 patients with ulcer, but with no bleeding. Prior to
      endoscopy they had completed a questionnaire about demographics, risk factors and
      habits. The platelet function, von Willebrand factor (vWF) and blood groups were
      determined. Histopathological analysis of biopsy samples were performed with a
      modified Sydney system. The influence of bile reflux was analyzed by Bile reflux
      index (BRI). RESULTS: Age, gender, tobacco and alcohol use did not affect the
      bleeding rate. The risk of bleeding did not depend on concomitant diseases (p =
      0.509) and exposure to stress (p = 0.944). Aspirin was used by 16/48 (33.3%)
      patients with bleeding ulcer, as opposed to 7/47 (14.9%) patients who did not
      bleed (p = 0.036). Abnormal platelet function had 12/48 (25.0%) patients who
      bled, as opposed to 2/47 (4.3%) patients who did not bleed (p = 0.004). Patients
      with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023).
      There was no statistical difference between groups in regards to blood groups and
      range of vWF. Antrum atrophy was found in 14/48 (29.20%) patients with bleeding
      ulcer and in only 5/47 (10.6%) patients who had ulcer without bleeding (p =
      0.024). CONCLUSION: Abnormal platelet function, aspirin use and antrum atrophy
      were the risk factors for ulcer bleeding in non-H. pylori, non- NSAIDs ulcer
      disease.

PMID- 24665578
TI  - Exercise-induced bronchoconstriction and non-specific airway hyperreactivity in
      patients suffering from bronchial asthma.
AB  - BACKGROUND/AIM: Physical activity is a common stimulus of asthmatic symptoms
      manifestation. Airway hyperreactivity is a predisposing cause of exercise induced
      bronchial obstruction, diagnosed by histamine inhalation. The aim of this study
      was to determine the relation between the amounts of histamine needed to induce
      non-specific airway hyperreactivity and exercise-induced bronchial obstruction.
      METHODS: This randomized cross-over study included 160 male patients (age 19-27
      years) suffering from bronchial asthma who showed positive results as the
      reaction after the histamine bronchial provocation test. Histamine concentrations
      were in a range of 0.03 to 4 mg/mL. Each patient participated in the exercise
      stress test conducted on a conveyor belt. The results of the exercise stress test
      were considered positive if the FEV1 level dropped by at least 15% from its
      initial value, 5-10 minutes after the test. RESULTS: All the patients showed
      positive results as the reaction after the histamine bronchial provocation test,
      while 50 of them showed positive results after the exercise-induced stress test.
      There was a statistically highly significant difference in administrated
      histamine concentrations between the group of patients that had positive results
      on exercise stress test and those who did not (1 mg/mL vs 0.5 mg/mL; U = 1678; p
      < 0.01). Also, there was a statistically significant difference concerning the
      frequency of the positive results regarding histamine concentration after induced
      stress test (chi2 = 10.885; p = 0.001). Among the patients with positive results,
      there was a statistically highly significant number of patients with bronchial
      obstruction induced by less than 2 mg/mL of histamine (p < 0.01). A statistically
      significant relation between the amount of histamine needed to induce bronchial
      obstruction and the results of the exercise stress test (p < 0.01) was also
      observed after the testing. CONCLUSION: In the group of patients with positive
      results after the exercise-induced stress test, there were significantly more
      patients with positive results to non-specific bronchial provocation test with
      lower histamine concentrations. Histamine concentrations needed to induce non
      specific hyperreactivity of asthmatic airway were shown to be related to the
      reactivity to physical effort.

PMID- 24665579
TI  - Hippocampus--why is it studied so frequently?

PMID- 24665580
TI  - Human case of fasciolosis in Serbia treated with triclabendazole.
AB  - INTRODUCTION: The number of humans infected by Fasciola hepatica is increasing
      worldwide. Humans can become accidental hosts by ingesting drinking water or
      plants contaminated with metacercariae. CASE REPORT: We reported a case of a 68
      year-old Serbian woman, in which the diagnosis of acute fasciolosis had been
      established after serious diagnostic concerns. Based on clinical picture
      (episodic right upper quadrant abdominal pain, febrility and generalized body
      pain) and biochemical analyses (high eosinophilia and high activity of alkaline
      phosphatase), she was appointed as suspected to the acute fasciolosis. Stool and
      duodenal aspirate exams were negative for Fasciola ova. In the absence of
      adequate serologic diagnostic for fasciolosis in Serbia, the diagnosis was
      confirmed using enzyme immunoassays and immunoblot at the Institute for Tropical
      Diseases in Hamburg, Germany. Soon after triclabendazole was administered, the
      symptoms disappeared and biochemical values returned to normal. CONCLUSION: The
      diagnosis of human fasciolosis may be problematic and delayed, especially in non
      endemic areas, because physicians rarely encounter this disease and a long list
      of other diseases must be considered in the differential diagnosis. The syndrome
      of eosinophilia, fever, and right upper quadrant abdominal pain suggest acute
      fasciolosis. Unclear source does not rule out fasciolosis.

PMID- 24665581
TI  - Switch to hypomania induced by repetitive transcranial magnetic stimulation and
      partial sleep deprivation added to antidepressant: a case report.
AB  - INTRODUCTION: Bipolar depression is often unrecognized and difficult to treat
      because of two opposite problems: treatment resistance and risk of manic switch.
      CASE REPORT: A 53-year-old female was suffering from unipolar depressive disorder
      since the age of 36. During a recent major depressive episode pervasive feelings
      of sadness, lost of interest in activities, severe insomnia and highly expressed
      somatic anxiety dominated 7 months. After unsuccessful tries with two different
      antidepressants of adequate doses and duration, slow rate repetitive trascranial
      magnetic stimulation (rTMS) was started, but the patient stayed at the fixed dose
      of antidepressant. Partial sleep deprivation (PSD) was additionally applied twice
      during these 2 weeks with the idea to boost up, or enhance rTMS treatment
      response. At the last two rTMS sessions depression obviously meliorated, but the
      patient also expressed symptoms of hypomania. The therapy of rTMS was stopped,
      hypomanic symptoms gradually vanished and two weeks after the rTMS treatment the
      patient was euthymic. Antidepressant was kept on. In a follow-up period of 2
      years the diagnose of bipolar affective disorder was definitely established.
      CONCLUSION: This case report shows that a combination of slow rate rTMS and
      partial sleep deprivation in the patient at the fixed dose of antidepressants,
      have strong synergistic effect even with potential to induce hypomanic switch,
      that is the first description in the literature to our knowledge.

PMID- 24665582
TI  - Renal dysplasia with the ipsilateral ectopic ureter mimicking abscess of the
      prostate.
AB  - INTRODUCTION: In males the ectopic ureter usually drains into the prostate (50%).
      During ureteric developement a thin membrane (Chawalla's membrane) separates the
      lumen of the ureter and the urogenital sinus at the point where the ureter joins
      the urogenital sinus. This membrane ruptures allowing urin to drain from the
      ureter to the urogenital sinus. The authors reported a case of renal dysplasia
      associated with ipsilateral uretral ectopia mimicking prostatic abscess. CASE
      REPORT: A subfebrile (37.3 degrees C), 23-year-old patient, otherwise healthy,
      presented with persistent ascending perineal pain non-responsive to antibiotics
      and analgetics. Digitorectal examination (DRE) showed asymmetric prostate with a
      soft, tender, buldging left lobe suggestive of prostatic abscess. The diagnosis
      was suspected using transrectal ultrasonography (TRUS), but the picture of the
      anechoic tubular structure in the left lobe of the prostate with a proximal
      undefined extraprostatic extension and a caudal intraprostatic blind end was
      incoclusive for the definitive diagnosis of prostatic abscess. Magnetic resonance
      imaging (MRI) was ordered and definitive diagnosis of renal dysplasia associated
      with the ipsilateral ectopic ureter filled with inflamed content mimicking
      prostatic abscess was made. Transurethral incision/minimal resection of the
      distal, blindly closed end of left ectopic ureter was done. Endoscopic surgical
      treatment was sufficient for relief of clinical symptoms. The patient's recovery
      was uneventful. CONCLUSION: To the best of our knowledge, a case of renal
      dysplasia with the ipsilateral ectopic ureter mimicking prostate abscess has not
      been reported so far. Cystic pelvic malformations in males may result from too
      cranial sprouting of the ureteral bud, with delayed absorption and ectopic
      opening of the distal end of the ureter.

PMID- 24665583
TI  - Recurrent herpes zoster with segmental paresis and postherpetic neuralgia.
AB  - INTRODUCTION: Postherpetic neuralgia and segmental paresis represent rare
      complications of herpes zoster infection. Recurrent herpes zoster is also rare
      and occurs within the first 3 years of the beginning of the illness in only 1.40%
      of cases but it is generally higher in cases of chronic lymphatic leukemia
      (3.5%). CASE REPORT: We presented a patient with lymphatic leukemia who during
      the remission had 3 episodes of herpes zoster over a year. All of them took
      different parts of the body. One of these episodes was complicated by
      postherpetic neuralgia and segmental paresis. A complete recovery was seen in all
      the three episodes. CONCLUSION: As immunosuppression is one of mechanisms of
      virus reactivation, it is likely associated with the described rare complications
      of herpes zoster.

PMID- 24665584
TI  - Assessment of cardiomyopathies presenting with myocardial infarction-like
      clinical syndrome.

PMID- 24665585
TI  - Authors' reply.

PMID- 24665586
TI  - [The JAID/JSC Guideline to Clinical Management of Infectious Diseases
      (Respiratory infections)].

PMID- 24665587
TI  - [Long effect of a booster on rubella antibodies from each original HI titer
      following vaccination].
AB  - This study was performed to clarify which titers of a pre-existing antibody could
      be efficiently boosted by vaccination and to assess the persistence of the
      antibodies. Two hundred healthy volunteer students with HI antibody titers of <
      or = 1:32 were enrolled. There were 6-16% of subjects with the negative HI
      antibody who had B-cell memory against rubella, because the EIA-IgM antibody
      remained negative and/or the avidity of the EIA-IgG antibody was high after
      vaccination. Furthermore most of them had already been vaccinated just once
      before. The ratio of those in whom the antibody levels increased significantly at
      one month after vaccination were 98%, 87%, 67% and 32% in subjects with an HI
      antibody titer of <1:8, < or =1: 8, < or =1:16 and < or =1:32 at pre-vaccination,
      respectively. The titers decreased significantly at two years after vaccination,
      however the ratio of decrease under each original level being 4%, 21.9%, 42.6%
      and 73.5% in each group of <1:8, < or =1: 8, < or =1:16 and < or = 1: 32,
      respectively. In comparison with the numbers of the subjects with <1: 8, the ones
      with < or = 1: 8, < or = 1:16 and < or = 1:32 increased 1.5-, 2.5- and 4.7-fold,
      respectively. Therefore, the recommendation of an HI antibody titer < or = 1:16
      for vaccination in Japan is thought to be loose, although this is to decrease the
      risk of congenital rubella syndrome. We think that a new assay for cellular
      immunity for rubella should be developed in the future in order to ascertain
      whether congenital rubella syndrome will be prevented or not.

PMID- 24665588
TI  - [Comparison of the kinetics of granulocytes and lymphocytes between influenza
      A/H1N1/pdm09 and seasonal influenza A].
AB  - Peripheral blood tests are performed for the differentiation of febrile diseases,
      and are useful for diagnosing and determining the effectiveness of treatment in
      bacterial infections. However, their use for viral infections has not been well
      investigated, nor do any clear views exist regarding their use with viral
      infections. We retrospectively investigated the results of routine peripheral
      blood tests for febrile diseases (differential leukocyte count and C-reactive
      protein (CRP)) performed in 1162 patients between the 2004/05 and 2009/10
      influenza seasons, and identified the characteristic findings of influenza, along
      with the differences between cases of seasonal influenza A (including H3N2 and
      H1N1; hereafter, seasonal A; n = 614) and pandemic influenza (H1N1) 2009 seen
      during the 2009/10 influenza season (hereafter, A/H1N1/pdm09; n=548). The
      differential leukocyte count varies with age; therefore, analysis was performed
      by adjusting for the age of all patients using a generalized additive model
      (GAM). Increased granulocytes and decreased lymphocytes were confirmed during the
      initial stage of influenza infection, followed by inversion to decreased
      granulocytes and increased lymphocytes. The granulocyte count was significantly
      lower in A/H1N1/pdm09 compared to seasonal A, with levels 0.93- and 0.82-fold
      relative to seasonal A before and after treatment, respectively. The lymphocyte
      count was 1.12- to 1.30-fold greater in A/H1N1/pdm09 compared to seasonal A both
      before and after treatment, indicating significantly higher levels in
      A/H1N1/pdm09. CRP levels peaked 24-36 h after onset, with peaks of 0.88mg/dL for
      A/H1N1/pdm09 and 1.53 mg/dL for seasonal A. Peripheral blood counts change due to
      factors such as the time course of the disease, onset of complications,
      modification resulting from treatment, and side effects of pharmacotherapies. We
      report the present findings because we consider an understanding of the changes
      and kinetics of differential leukocyte counts in peripheral blood inherent to
      influenza to be important for diagnosis (particularly for the decision of doing
      rapid diagnosis test) and to promote recognition of the onset of complications
      and side effects during the course.

PMID- 24665589
TI  - [A case of spinal tuberculosis in a young Filipino man].
AB  - A 19-year-old Filipino man was admitted to our hospital because of persisting
      fever and back pain. He had recognized his symptoms 6 months previously, but a
      definite diagnosis was not made. Image testing demonstrated a compressed fracture
      of the thoracic vertebrae accompanied with a perivertebral abscess. A biopsy
      specimen revealed granuloma compatible with tuberculosis (TB). Anti-TB drugs were
      initiated, and his clinical symptoms steadily improved. However, he developed
      neuropathic symptoms due to exacerbation of the abscess two months after starting
      the anti-TB drugs. An immediate laminectomy was performed resulting in symptom
      relief; however severe kyphosis remained. Polymerase chain reaction testing of
      the abscess collected during the operation was positive for Mycobacterium
      tuberculosis, confirming the diagnosis of spinal TB. The diagnosis of spinal TB
      has been a challenge world-wide. Clinicians should be aware of the demographic
      background as well as the clinical and laboratory features of spinal
      tuberculosis, facilitating earlier diagnosis.

PMID- 24665590
TI  - [Bacteriologic characteristics of Arcanobacterium haemolyticum isolated from
      patients with soft tissue skin infection].

PMID- 24665591
TI  - [The psychological characteristics of the patents presenting with pain syndrome].
AB  - The psychological characteristics of 336 patients presenting with chronic somatic
      diseases and long-standing pain syndrome were analysed. It was found that the
      severity of pain is related to the combination of hypochondriacal, anxious and
      depressive disorders with rigidity and the tendency toward the formation of
      various fixations. The impaired quality of life in these patients was
      attributable to their dissatisfaction about limitations of daily physical
      activity and communication, as well as to the attitude of the relatives that
      changed after the disease was confirmed.

PMID- 24665592
TI  - [Accommodation effects of the audiovisual stimulation in the patients
      experiencing eyestrain with the concomitant disturbances of psychological
      adaptation].
AB  - The present study was designed to evaluate the effectiveness of audiovisual
      stimulation on the state of the eye accommodation system in the patients
      experiencing eyes train with the concomitant disturbances of psychological. It
      was shown that a course of audiovisual stimulation (seeing a psychorelaxing film
      accompanied by a proper music) results in positive (5.9-21.9%) dynamics of the
      objective accommodation parameters and of the subjective status (4.5-33.2%).
      Taken together, these findings whole allow this method to be regarded as
      "relaxing preparation" in the integral complex of the measures for the
      preservation of the professional vision in this group of the patients.

PMID- 24665593
TI  - [The application of transcranial magnetic stimulation for the functional
      diagnostics of motor disturbances in the patients presenting with ischemic
      stroke].
AB  - AIM: To estimate the informative value of transcranial magnetic stimulation (TMS)
      as a tool for the functional diagnostics of motor disturbances and to evaluate
      its remedial potential in the patients presenting with ischemic stroke (IS) and
      motility disorders in the acute phase of the disease and during the early
      rehabilitation period. MATERIALS AND METHODS: The present study included the
      comprehensive examination of 112 patients (mean age 59.2 +/- 5.67 years) with the
      newly emerged hemispheric IS in the basin of the right (n = 53) and left (n = 59)
      middle cerebral artery (MCA) in the acute phase of the disease and during the
      early rehabilitation period associated with a moderate neurologic deficit.
      Moreover, TMS was used to examined 30 subjects (mean age 57.8 +/- 4.33 years)
      presenting without neurological pathology who comprised the control group for the
      comparison of the motor evoked potentials (MEP). Correlation between different
      MEP values and numerical score estimates of neurological deficit based on the NIH
      stroke scale was calculated using nonparametric Spearman's correlation
      coefficient. RESULTS: In 42 (34.4%) patients with IS, MEP on the affected side
      were missing which was later manifested as the low rehabilitative potential for
      the restoration of the motor functions. In 70 of the 112 patients (65.6%) MEP
      were registered from the paretic limbs by TMS of the motor centers of the
      affected hemisphere even though with a decreased amplitude and increased latency
      that facilitated the well apparent recovery of the motor function during the
      rehabilitation process in these patients (from 5.4 +/- 0.3 points to 1.3 +/- 0.5
      points, p < 0.05). The persistence of MEP during TMS of the affected hemisphere
      in the patients with IS can be considered as the conservation of the
      rehabilitation potential for the recovery of the motor functions. All the time
      amplitude parameters of MEP in the upper extremities significantly correlated
      with the NIHSS scores. In the lower extremities correlation was statistically
      significant for the MEP amplitude parameters and the latency difference between
      the affected and unaffected sides. CONCLUSION: TMS with the determination of the
      time and amplitude parameters of MEP is a sensitive method for the quantitative
      assessment of the functional status of the motor system in the patients
      presenting with ischemic stroke and motility disorders in the acute phase of the
      disease and during the early rehabilitation period.

PMID- 24665594
TI  - [The clinical and functional rationale for the application of the baths
      containing the Siberian Stag velvet antler extracts in the rehabilitative
      treatment of the patients presenting with arterial hypertension and concomitant
      chronic psychoemothional overtension].
AB  - We have developed the method for the treatment of the patients presenting with
      arterial hypertension and concomitant chronic psychoemothional overtension. The
      method consists of the application of the baths containing the Siberian Stag
      velvet antler extracts in combination with exercise therapy and massage. A total
      of 35 patients with arterial hypertension and concomitant chronic
      psychoemothional overtension were enrolled in the study. It was shown that
      inclusion of the baths containing the Siberian Stag velvet antler extracts in the
      combined treatment of arterial hypertension and concomitant chronic
      psychoemothional overtension has positive effect on the parameters of the main
      homeostatic systems, enhances the working capacity of the patients, promotes
      their psychological stability, and increases the adaptive potential of the
      organism.

PMID- 24665595
TI  - [The influence of the pearl baths on the dynamics of cerebral circulation in the
      children presenting with the consequences of perinatal lesions in the central
      nervous system].
AB  - The present article is concerned with the problem of rehabilitation of the
      children at the age from 6 to 12 months presenting with perinatal lesions in the
      central nervous system (CNS) and the role of cerebral hemodynamics in the
      development of this disease. The results of dynamic clinical and laboratory
      examination of the children presenting with the consequences of perinatal lesions
      in the central nervous system are presented with special reference to the
      influence of the pearl baths on the dynamics of cerebral circulation. The study
      involving 65 patients showed that the inclusion of bubble bath sin the combined
      rehabilitative treatment of the children with this condition helps to optimize
      parameters of the disturbed cerebral blood flow. The positive influence of bubble
      bath son the dynamics of clinical symptoms and the state of the cardiovascular
      system has been demonstrated.

PMID- 24665596
TI  - [The role of therapeutic exercises in the correction of the static component of
      the motor stereotype in the patients presenting with cervical myofascial pain
      syndrome].
AB  - The present study was designed to estimate the influence of various modalities of
      therapeutic exercises on the static component of the motor stereotype in 200
      patients presenting with cervical myofascial pain syndrome. The study was
      performed with the use of computed optical topography. The course of therapeutic
      exercises included 10 sessions of the total duration of 14 days. It is concluded
      based on the data obtained in this study that remedial gymnastics based on the
      understanding of the internal body model ("body scheme") with the use of static
      symmetric exercises is 2.7 times as effective as the traditional approach.

PMID- 24665597
TI  - [The effectiveness of the spa and resort-based health-promoting treatment of the
      schoolchildren under conditions of the continuous academic process].
AB  - Two groups of schoolchildren were included in the present study; 59 of them were
      allocated to the experimental group while 66 others comprised the control group.
      All of them were examined to estimate psychological, psycho-physiological and
      physiological effects of the health-promoting treatment basedon a local health
      resort. Mean reaction time and mean root square deviation of this parameter
      determined with the use of the noise-immunity test improved significantly in both
      groups, but the number of 'late reaction' errors declined only in the
      experimental group. The analysis of the heart rate variability at rest
      demonstrated a significant increase of the total power spectrum as well as its
      very low-, low-, and high-frequency components in the supine position only in the
      experimental group but not in the control one. Moreover, the mean duration of
      cardiointervals also increased. The physical working capacity test showed a
      significantly enhanced working capacity in the treated children. The orthostatic
      test revealed an increase in the ratio of low-frequency/high-frequency components
      and a relative increase of the high-frequency component in the experimental group
      the amplitude of the transition process in the control group. The results of the
      study confirm the overall positive effects of the health promotion in
      schoolchildren presenting with heart rate variability treated at the local health
      resort on their psycho-physiological and physiological conditions, with the heart
      rate variability patterns being the most informative objective criteria of the
      physiological responsiveness.

PMID- 24665598
TI  - [Variations of the volume and segmental blood flow in the upper extremity of the
      patents presenting with breast cancer treated with the application of various
      regimes of pneumatic compression].
AB  - Post-mastectomy lymphedema on the side of the surgical intervention is a major
      complication of radical therapy of breast cancer patients. Pneumatic compression
      (compression pump technology) of various types, modes and techniques is used for
      their rehabilitation. A total of 192 breast cancer patients with I-IV degree
      lymphedema were available for the examination in the present study. All of them
      were treated with the application of different modes of one- and multi-chambered
      pneumatic compression. Based on the results of aqueous and impedance
      plethysmography, the multi-chambered pneumatic compression was identified as the
      most effective methods for the purpose, with the pressure inside the chambers
      below 60-80 mm Hg and the duration of the treatment 45-60 min per day. It is
      recommended to perform three treatment courses each consisting of 15 procedures
      with the intervals of 3-6 months between them (depending on the severity of the
      edema).

PMID- 24665599
TI  - [The pathogenetic rationale for the application of reflexotherapy in the
      rehabilitation of the patients presenting with cognitive disorders].
AB  - Cognitive disorders (CD) of variable severity are currently one of the leading
      causes of disability in the patients presenting with vascular and degenerative
      diseases of the brain; it is especially true of Alzheimer's disease. The
      discovery of the universal pathogenetic mechanism underlying the development of
      CD made it possible to explain the known cases of the successful application of
      acupuncture in the patients with disorders of seemingly different origin. The
      results of these studies suggest that acupuncture can affect the key pathogenetic
      "functional circles" involved in the development of CD. The present article is
      focused on the description of the humoral, neurotransmitter and
      electrophysiological mechanisms through which the positive effects of acupuncture
      on the cognitive function of the patients with various diseases are mediated.

PMID- 24665600
TI  - [50 years of the methodology of weather forecasting for medicine].
AB  - The materials reported in the present article illustrate the possibility of
      weather forecasting for the medical purposes in the historical aspect. The main
      characteristics of the relevant organizational and methodological approaches to
      meteoprophylaxis based of the standard medical forecasts are presented. The
      emphasis is laid on the priority of the domestic medical school in the
      development of the principles of diagnostics and treatment of meteosensitivity
      and meteotropic complications in the patients presenting with various diseases
      with special reference to their age-related characteristics.

PMID- 24665601
TI  - [Professor Aleksandr Efimovich Shcherbak and his role in the development of
      physiotherapy in Russia as estimated by contemporaries (on the occasion of his
      150th birthday anniversary)].

PMID- 24665602
TI  - Association of the use of statins with disease activity and functional status in
      Puerto Ricans with rheumatoid arthritis.
AB  - OBJECTIVE: Statins, which appear to have anti-inflammatory and immunomodulatory
      effects, may benefit patients with rheumatoid arthritis (RA). Our study sought to
      determine the association of statins use with disease activity and functional
      status in a group of patients with RA. METHODS: A cross-sectional study was
      performed in 209 Puerto Ricans with RA (per the 1987 classification criteria of
      the American College of Rheumatology). Demographic features, lifestyle-related
      behaviors, disease activity (per Disease Activity Score 28), comorbid conditions,
      functional status (per Health Assessment Questionnaire), pharmacologic therapy,
      and patients' and physicians' global assessments using visual analogue scales,
      were determined. Data were examined using univariate, bivariate, and multiple
      logistic regression analyses. RESULTS: The mean (standard deviation [SD]) age of
      the study population at study visit was 56.8 (13.5) years (range: 24-86 years);
      175 patients (83.7%) were women. The mean (SD) disease duration was 10.4 (9.5)
      years (range: 0.0-44.0 years). Thirty-two (15.3%) patients were using statins at
      study visit, and 36 (17.2%) had used statins in the past. In the multivariable
      analysis, the current use of statins was associated with higher functional status
      (odds ratio 0.42, 95% confidence interval 0.22-0.80) than was nonuse, after
      adjusting for age, disease duration, arterial hypertension, coronary artery
      disease, and dyslipidemia. No association between either current or past use of
      statins and disease activity was found. CONCLUSION: In this group of RA patients,
      the current use of statins was associated with a higher functional status;
      conversely, no association was found between statins use and disease activity.
      However, larger and longitudinal studies are required to confirm these findings.

PMID- 24665603
TI  - Prevalence of hypodontia in 10- to 14-year-olds seeking orthodontic treatment at
      a group of clinics in Puerto Rico.
AB  - OBJECTIVE: To estimate the prevalence of hypodontia in a group of 10- to 14-year
      olds from a group of orthodontic clinics in Puerto Rico. METHODS: A cross
      sectional study was conducted to estimate the prevalence of hypodontia in 10- to
      14-year-olds from orthodontic clinics located in each of 9 regions (as determined
      by the government-run health insurance program, Reforma) in Puerto Rico. A total
      of 1,911 patients, ranging in age from 10 to 14 years, were evaluated using
      patient charts covering from May 2004 through June of that same year. A logistic
      regression model was done to evaluate the relation between the prevalence of
      hypodontia in the study group and clinic location, gender, and age; a 5%
      significance level was used. RESULTS: The overall weighted prevalence of
      hypodontia was 6.02%. Females showed a higher weighted prevalence of hypodontia
      than did males (7.02% vs. 4.72%, respectively: p = 0.06). The prevalence also
      varied by geographic region, ranging from 3.21% at the San Juan clinic to 10.68%
      at the Aibonito clinic (p = 0.01). The most prevalent missing teeth were the
      maxillary lateral incisors, followed by the lower second premolars (1.9%).
      CONCLUSION: The prevalence of hypodontia in Puerto Rico was 6.02%. Females
      presented a higher prevalence of hypodontia than did males. Each of the clinics
      in Fajardo, Bayamon, San Juan, and Guayama had a lower prevalence of hypodontia
      than the Aibonito clinic did. The tooth most frequently missing in the study
      group was the maxillary right lateral incisor.

PMID- 24665605
TI  - Mohs micrographic surgery: 10 year experience in Puerto Rico.
AB  - OBJECTIVE: The incidence of nonmelanoma skin cancer (NMSC) is increasing rapidly
      worldwide. As NMSC incidence increases, the modalities to treat this condition
      have become diverse. However, Mohs surgery remains the standard treatment for
      skin cancer in several particular locations such as the face. The objective of
      this study is to compare the changes, occurring over a 10-year period, in the
      characteristics of those cancers that were treated with Mohs micrographic surgery
      (MMS) at the dermatology clinics of the University of Puerto Rico as well as the
      modifications in the repair patterns used to close the surgical defects. METHODS:
      A retrospective chart review of patients treated with MMS at the dermatology of
      the University of Puerto Rico in the years 2000 and 2010. Variables analyzed
      include patient demographics, the anatomic site of each patient's lesion,
      pathology, the preoperative tumor size, the postoperative defect size, and the
      repair method. RESULTS: Thirty-eight (38) patients in the year 2000 and 55
      patients in the year 2010 were treated with MMS, signifying a 44% increase in
      this kind of treatment over a 10-year period. The 2000 cohort was found to be
      slightly older (P = 0.22), with no gender predominance (P = 0.44). In both years,
      the majority of tumors were located on the head and neck region, being the nose
      the most frequent site of involvement (P = 0.06). Basal cell carcinoma (BCC) was
      the most common neoplasm (P = 0.65). No statistical difference was found in
      preoperative tumor sizes (P = 0.27). More stages were required to remove a given
      tumor completely in the year 2000 (P = 0.025). Postoperative defects were smaller
      in 2000 (P = 0.027) than they were in 2010. Flap repair was used more often in
      2010 (P = 0.001) than in 2000. CONCLUSION: This study shows a trend toward larger
      defects in a slightly younger population of patients in the 2010 cohort compared
      to the 2000 cohort. It also demonstrates a reduction in the number of stages
      required to excise the tumors, and a tendency to reconstruct the surgical defects
      with flaps. However, the tumor types, preoperative tumor sizes, and anatomic
      sites of the lesions were all similar in the 2 cohorts.

PMID- 24665604
TI  - Physical environment, diet quality, and body weight in a group of 12-year-old
      children from four public schools in Puerto Rico.
AB  - OBJECTIVE: Physical environment influences diet and has been proposed as a
      determinant of childhood obesity. This cross-sectional study explored physical
      environment and its associations with diet quality and weight status in a sample
      of 114 12-year-old children from 4 public schools in the metropolitan area of San
      Juan, PR. METHODS: Physical environment was assessed by asking questions
      regarding the availability and accessibility of healthy and unhealthy foods and
      food outlets as well as of recreational and sports facilities and equipment. Food
      intake was determined using a 24-hour diet-recall questionnaire, with the
      gathered data being used to assess diet quality and calculate the Healthy Eating
      Index (HEI)-2010. The HEI includes 12 components that are used to determine the
      compliance of a given diet with federal guidelines. HEI-2010 total score ranges
      from 0 to 100 and is divided into the following classifications: poor (< or =
      50), needs improvement (51-80), and good (> 80). Body mass index was computed
      using measured weight and height and categorized according to the CDC Growth
      Charts. RESULTS: Thirty-six percent of the participating children were overweight
      or obese. Nearly 57% had poor diet quality. The lowest HEI-2010 component scores
      were found for total fruits, whole fruits, total vegetables, whole grains,
      seafood and plant proteins, and fatty acids. However, diet quality was not
      associated with weight status or physical environment factors. Compared to the
      other children in the study, overweight or obese children reported having a
      significantly (p < 0.05) lower availability of unhealthy foods and the highest
      access to recreational and sports facilities at home but also lower utilization
      of recreational and sports facilities at school and reduced participation in the
      school breakfast program. CONCLUSION: This study showed that some home- and
      school-environment factors influenced body weight in the children in this sample.
      However, these same factors did not appear to affect diet quality.

PMID- 24665606
TI  - Granulomatous enterocolitis secondary to Yersinia in an 11-year-old boy from
      Puerto Rico, confirmed by PCR: a case report.
AB  - We report the case of an 11-year-old boy without any history of systemic illness
      and who developed fever and chills and experienced a 10 lbs. weight loss 3 weeks
      prior to admission. Two days before admission, he experienced abdominal pain that
      became localized to the right lower quadrant within 24 hours. A non-enhanced
      abdominal computed tomography scan revealed a 5 mm, amorphous, hyperdense, right
      lower quadrant calcification associated with a 9 mm fluid-filled structure. An
      exploratory laparotomy revealed thickening of the proximal vermiform appendix
      extending to the cecum, with mesenteric adenopathy. An en-bloc excision of the
      distal ileum, cecum, mesocolon, and vermiform appendix with an end-to-end ileo
      ascending colon anastomosis was performed because of a suspected neoplasm.
      Pathologic examination of the specimen revealed granulomatous enterocolitis with
      associated acute suppurative appendicitis and a cecum abscess. Polymerase chain
      reaction analysis of a paraffin-embedded tissue block confirmed Yersinia
      enterocolitica DNA in the tissue, pointing to Yersinia as being the etiologic
      microbe. To our knowledge, this is the first case of yersiniosis to be reported
      in Puerto Rico.

PMID- 24665607
TI  - [Application of MSCT's coronary artery calcification score in evaluation of
      sudden death caused by coronary artery disease].
AB  - OBJECTIVE: To access application value of multi-slice spiral computed tomography
      (MSCT) and coronary artery calcium scoring (CACS) in investigation the coronary
      artery disease (CAD), and to explore the effective way of virtual autopsy to
      evaluate the sudden death due to CAD. METHODS: Nine cases of sudden cardiac death
      were collected to analyze MSCT before the autopsy. The quantitative analysis of
      the degree of coronary artery calcium was made by Agatston's method. The CACS of
      all the subjects were calculated based on the diagnostic criteria for CAD, in
      which calcium scoring was more than 400. The results of CACS were compared with
      that of the autopsy. RESULTS: Only 2 cases got the high calcium scoring which
      were more than 400 in the 9 cases died of CAD confirmed by the autopsy. The
      prediction rate of CACS for CAD was only 22.2%. Pulmonary edema of different
      severity was found in both autopsy and MSCT. There was a higher morbidity rate in
      the left anterior descending of coronary artery than the other branches.
      CONCLUSION: Obvious calcification of coronary artery can be detected by MSCT and
      calculating CACS. To detect subtle calcification needs other technologies such as
      postmortem angiography.

PMID- 24665608
TI  - [Changes of postmortem human blood biochemical indexes].
AB  - OBJECTIVE: To investigate and analyze the changes of postmortem human biochemical
      indexes. METHODS: Subclavian venous blood samples were collected from 81 cases of
      traffic fatalities. Thirteen blood biochemical indexes including liver function
      (ALT, AST, TBIL and DBIL), renal function (UA and Cr), cardiac function (CK, CK
      MB and LDH), electrolytes (K+, Na+ and Cl-), and glucose (GLU) were tested by
      Roche cobas c311 automatic biochemical analyzer. The descriptive analysis was
      made by SPSS 17.0 statistical software. RESULTS: The values of ALT, AST, CK, CK
      MB, LDH and K+ were higher than normal reference values with more fluctuations.
      The values of TBIL, DBIL, UA, Cr, Na+, Cl- and GLU were relatively stable with
      less fluctuations. CONCLUSION: The postmortem human blood biochemical indexes of
      liver function, renal function, cardiac function, electrolytes and glucose could
      be affected by the factors, especially hemolysis and autolysis. The biochemical
      indexes, particularly enzymes, increased significantly with higher standard
      deviation.

PMID- 24665609
TI  - Reliability study on quantitative detection of extensor digitorum brevis strength
      with needle electromyography and nerve conduction.
AB  - OBJECTIVE: To study the objectivity and reliability of needle electromyography
      and nerve conduction for detection of musculus extensor digitorum brevis
      strength, which may provide a basis for establishing a quantitative detection of
      muscle strength in forensic clinical study. METHODS: Forty-four healthy people
      were enrolled as the subjects, and during toe dorsiflexion, the following items
      including needle electromyography indexes, motor unit potential (MUP) amplitude,
      MUP count, recruitment reaction type, and nerve conduction detection indexes,
      compound muscle action potential (CMAP) amplitude, CMAP latent period and motor
      nerve conduction velocity (MNCV), were simultaneously detected under the
      cooperation and disguise condition. RESULTS: Under the cooperation condition,
      regardless of the same operator or different operators, there were good test
      retest reliabilities in MUP amplitude, CMAP amplitude, CMAP latent period and
      MNCV, while there were normal test-retest reliabilities in MUP count and
      recruitment reaction type and the repeatability of the same operator was slightly
      better than the repeatability between different operators. Under the disguise
      condition, test-retest reliabilities of MUP amplitude, CMAP amplitude, CMAP
      latent period and MNCV were relatively high, while test-retest reliabilities of
      MUP count and recruitment reaction type were relatively low. CONCLUSION: There
      are good test-retest reliabilities in MUP amplitude, CMAP amplitude, CMAP latent
      period and MNCV, which can be conducive to comparison between different operators
      and results at various times; MUP count and recruitment reaction type, which can
      be easily affected by subjectivity of operators and examinees, can be used to
      differentiate whether an examinee disguises or not. The indexes used to
      objectively judge muscle strength remain to be further investigated.

PMID- 24665610
TI  - [Applicability of capacity of sexual self-defense assessment scale in psychiatric
      patients without mental retardation].
AB  - OBJECTIVE: To explore the applicability of Capacity of Sexual Self-defense
      Assessment Scale (CSSAS) in psychiatric patients without mental retardation.
      METHODS: Eighty-seven cases required for assessment of the capacity of sexual
      self-defense were collected and evaluated by trained professionals according to
      CSSAS, and the results were compared to the experts' opinions. RESULTS: The
      scores of three grades of capacity of sexual self-defense (none, limited and
      whole) were 5.97 +/- 5.83, 32.22 +/- 10.15 and 61.60 +/- 13.02, respectively,
      which were statistically significant among them (P < 0.01). The correlation
      coefficients between items and total score were 0.59 to 0.91, the Cronbach's
      alpha value was 0.96, the spilt half Cronbach's alpha value were 0.94 and 0.91,
      respectively, and the relation coefficient between them was 0.94. According to
      the original cut off scores, the Kappa value between scale results and experts'
      opinions was 0.32 (P < 0.01). By redefining the cut off scores, the Kappa value
      was improved to 0.84 (P < 0.01). Two factors were extracted by means of the
      factor analysis. The explanation rates of variance were 46.15% and 28.93%,
      respectively. The accuracy of retrospective cumulative square was 94.30%.
      CONCLUSION: The CSSAS could be applied in the psychiatric expertise of the
      capacity of sexual self-defense in psychiatric patients without mental
      retardation; however, the cut off scores and the factor weight should be
      redefined.

PMID- 24665611
TI  - [One-step methylation variable position analysis technology in single-tube].
AB  - OBJECTIVE: To develop the single-tube one-step methylation variable position
      (MVP) analysis technology-single-tube post-digestion PCR-melting curve analysis
      (PDP-MCA). METHODS: Based on differentially methylated region (DMR) reported
      previously as the model, a set of primers with different melting temperatures of
      products in the two sides of MVP were designed. By using the FastDigest
      methylation-sensitive restriction enzyme (MSRE), DNA digestion, multiplex
      amplification, MCA detection and MCA profiles were performed in a single reaction
      tube. Same samples (peripheral venous blood, semen, and vaginal fluid, 5 samples
      each type) were tested by single-tube one step MVP and traditional MSRE-PCR MCA
      technology. To verify the feasibility of this method, the results were compared
      with that of the traditional technology. The MCA/HRM profiles of different
      samples were analyzed and compared. RESULTS: When the melting temperature of the
      fragments had a differential of 2 degrees C, the MCA melting peaks separated
      well, and MCA detection after multiplex amplification was successful. The single
      tube PDP-MCA assay was developed, which integrated multiple reactions (digestion,
      amplification and detection) into one tube. By this method, the sample-specific
      profiles and data were analyzed in 2 h, which is similar to that of the
      traditional method. The rapid classifications of the samples were also realized.
      CONCLUSION: Multiplex MVPs can be analyzed in a single closed-tube. The single
      tube PDP-MCA technology is a simple, fast, and automatable method. It can be used
      for detection of DNA methylation variations.

PMID- 24665612
TI  - [Determination of 33 inorganic elements in human hair by electricity plate
      digestion and inductively coupled plasma-mass spectrometry].
AB  - OBJECTIVE: To establish the electricity plate digestion and inductively coupled
      plasma-mass spectrometry (ICP-MS) method for determination of 33 inorganic
      elements in human hair. METHODS: Lithium (6Li), Germanium (72Ge), Yttrium (89Y),
      Indium (115In), and Terbium (159Tb) were used as internal standards. The electric
      heating board digestion in a mixture of nitric acid and hydrogen peroxide was
      used as the pre-treatment of the hair. Thirty-three inorganic elements in human
      hair were analyzed by ICP-MS method. RESULTS: The detection limit of ICP-MS was
      0.0001 microg/g(Th)-10.9 microg/g (Ca) and the limit of quantitation was 0.0005
      microg/g (Th)-25 microg/g (Ca). The recovery rate of this method was 86%-113%.
      The RSD for the intra-day and inter-day were less than 9.2%. The method was not
      statistically different from microwave digestion method. CONCLUSION: This method
      is highly efficient and accurate. It can be used for analysis of 33 inorganic
      elements in human hair.

PMID- 24665613
TI  - [Forensic analysis of death caused by fat embolism: A study of 20 autopsy cases].
AB  - OBJECTIVE: To analyze the general and forensic pathological characteristics of
      death due to fat embolism syndrome (FES) and to provide reference data for
      forensic identification. METHODS: Twenty autopsy cases due to FES were selected
      from the forensic center of a medical college from 1999 to 2012. The general and
      forensic pathological characteristics such as the ways and types of injuries,
      clinical manifestation and the pathological changes were summarized. RESULTS: Fat
      embolism mainly occurred after long bone fracture or a large area of soft tissue
      injury with the majority of cases being fat embolism of lung and occasional cases
      being combined embolisms of lung and brain as well. The onset of symptoms
      appeared shortly after the injury or surgery. Lipid droplets could be observed
      within small pulmonary vessels and verified by special staining. CONCLUSION:
      There are particular characteristics in death due to FES in concern with types of
      injuries, onset of symptoms and pathological findings. In order to find out the
      direct evidence of FES, special staining (oil red O staining) can be used in the
      forensic identification.

PMID- 24665614
TI  - [A retrospective analysis of estimating postmortem interval in 256 murder cases].
AB  - OBJECTIVE: To discuss the method of reducing error in estimating postmortem
      interval (PMI). METHODS: Two hundred and fifty-six solved murder cases from 2003
      January to 2013 January in Changzhou and Nanjing City were collected, The PMI of
      all cases was estimated by traditional method and then compared with the real PMI
      obtained after the cases were solved. The cases were grouped according to the
      PMI, the accuracy was calculated, and the reasons of suboptimal PMI were
      analyzed. RESULTS: The accuracies of early PMI (less than 12h and 13-24 h) were
      90% and 89%, respectively; while the accuracies of late PMI (1-7 d, 1-2 weeks, 3
      4 weeks, 1-6 months, 7-12 months and 1-5 years) decreased over time, being 79%,
      76%, 83%, 79%, 60% and 50%, respectively. The common reasons of estimating error
      included improper inference methods, water submerged body, extreme temperature,
      lack of objective evidence, intentionally abandoned body, and changed or
      destroyed scene, etc. CONCLUSION: The multiple index data can reduce the error in
      estimating PMI.

PMID- 24665615
TI  - [Disability identification for cases with clinical diagnosis of diffuse axonal
      injury due to traffic accidents: a study of 89 cases].
AB  - OBJECTIVE: To study the disability identification for cases with clinical
      diagnosis of diffuse axonal injury (DAI) due to traffic accidents, and to explore
      the possible effects of DAI on identification results. METHODS: Five hundred and
      fifty-six cases of cerebral injury due to traffic accidents were collected,
      including 467 cases diagnosed with cerebral contusion or laceration and 89 cases
      diagnosed with DAI. The identification results of different groups with diagnosis
      of DAI diagnosis, diagnosis of DAI with cerebral contusion (laceration), and
      diagnosis of cerebral contusion or laceration without DAI were compared and
      statistically analyzed, based on the results of CT and MRI re-review. RESULTS:
      The disability identification levels in DAI group (20 cases), DAI group (69
      cases) with cerebral contusion (laceration) and DAI group (467 cases) not
      complicated by cerebral contusion (laceration) were 7.72 +/- 1.09, 7.78 +/- 1.11,
      and 8.86 +/- 0.66, respectively. The disability levels of the two groups
      diagnosed with DAI were higher than those of the group without DAI diagnosis (P <
      0.05). CONCLUSION: Patients with DAI diagnosis might have more severe cerebral
      injury. In the identification process, one should pay attention to the possible
      missed diagnosis and misdiagnosis, and meanwhile avoid relying on those evidences
      provided only by CT and MRI.

PMID- 24665616
TI  - [Genetic polymorphisms of 19 STR loci in Shandong Han population].
AB  - OBJECTIVE: To investigate the genetic polymorphisms of 19 STR Loci in Shandong
      Han population in order to provide the genetic data for paternity testing.
      METHODS: The genotypes of 205 unrelated individuals in Shandong Han population
      were typed by Goldeneye 20A kit to get the allele frequencies and population
      genetic parameters of 19 STR loci. Four kits, Identifiler kit, SinoFiler kit,
      PowerPlex 16 kit, and Goldeneye 20A kit, were compared with each other and used
      in the analysis of a special paternity test case. RESULTS: The population genetic
      parameters of 19 STR loci in Shandong Han Population were obtained. The
      cumulative discrimination power (CDP) and cumulative probability of exclusion
      (CPE) ranked from high to low were Goldeneye 20A kit, SinoFiler kit, PowerPlex 16
      kit and Identifiler kit, respectively. As duo case, the result of the real case
      showed that Identifiler kit had no excluding loci, and none of the SinoFiler kit,
      PowerPlex 16 kit or Goldeneye 20A kit could exclude fatherhood. CONCLUSION:
      Compared with Identifiler kit, SinoFiler kit, and PowerPlex 16 kit, Goldeneye 20A
      kit shows the higher efficiency than the others, but is not completely satisfied
      for duo cases.

PMID- 24665617
TI  - [Statistics analysis of tri-allelic patterns in STR loci].
AB  - OBJECTIVE: To investigate the statistical method of tri-allelic patterns of STR
      loci. METHODS: The DNAs of venous blood and blood stain samples from 8,846
      unrelated individuals were extracted using magnetic bead method, and STR
      genotypes were determined by multiplex fluorescent amplification and capillary
      electrophoresis and analyzed using GeneMapper ID v3.2 software. The genotype
      frequency and allele frequency of trizonal were determined by direct counting and
      formula, respectively, in order to deduce the formula of trizonal in paternity
      test and individual recognition. RESULTS: Of the 8,846 individuals, four tri
      alleles and three tri-genotypes were detected. The multiplying of allele
      frequency and actual rate showed significantly statistical difference. The
      formula of trizonal in paternity test and individual recognition was successfully
      deduced. CONCLUSION: The frequency of the two alleles inherited as a whole in the
      population could be calculated by multiplying the frequencies of each allele in
      the tri-allelic patterns.

PMID- 24665618
TI  - [Biological characteristics of calliphoridae and its application in forensic
      medicine].
AB  - Diptera Calliphoridae is the first major kind of flies that appears on the
      decomposed corpses. In forensic entomology, according to the living
      characteristics of Calliphoridae flies, we could accurately estimate postmortem
      interval (PMI) in a murder or unidentified case and could provide useful clues to
      solve the case. This paper introduces the characteristics of the biology and
      morphology of Diptera Calliphoridae, and reviews the combined application of
      forensic entomology, molecular biology, mathematical morphology and toxicology.

PMID- 24665619
TI  - [Progress on suxamethonium chloride analysis].
AB  - Abstract: Suxamethonium chloride is a depolarizing muscle relaxant used in
      general anesthesia. In overdose, it causes adverse reactions such as bradycardia,
      arrhythmia, cardiac arrest, and death. The article reviews the progress on
      testing methods of suxamethonium chloride such as infrared spectroscopy, chemical
      color reaction, chemical titration, enzyme electrode, chromatography and mass
      spectrometry.

PMID- 24665620
TI  - [Forensic evidence-based medicine in computer communication networks].
AB  - As an important component of judicial expertise, forensic science is broad and
      highly specialized. With development of network technology, increasement of
      information resources, and improvement of people's legal consciousness, forensic
      scientists encounter many new problems, and have been required to meet higher
      evidentiary standards in litigation. In view of this, evidence-based concept
      should be established in forensic medicine. We should find the most suitable
      method in forensic science field and other related area to solve specific
      problems in the evidence-based mode. Evidence-based practice can solve the
      problems in legal medical field, and it will play a great role in promoting the
      progress and development of forensic science. This article reviews the basic
      theory of evidence-based medicine and its effect, way, method, and evaluation in
      the forensic medicine in order to discuss the application value of forensic
      evidence-based medicine in computer communication networks.

PMID- 24665621
TI  - Genetic polymorphisms of 15 STR loci in Gansu Hui population.

PMID- 24665622
TI  - [Carcinogenicity of antineoplastic drugs: classification, protection and
      prevention, use and evidence].
AB  - Many antineoplastic agents have been shown to be mutagenic, teratogenic and
      carcinogenic in experimental studies and secondary malignant neoplasms are known
      to be associated with several specific therapeutic treatments. However, the
      occupational exposure to antineoplastic drugs in health care workers has
      different routes of exposure, dose and duration compared to patients undergoing
      treatment protocols. The aims of this review are to analyze and to update the
      National and International Classification, and deepening the topics of
      occupational exposure, current operating conditions, the technical and
      operational progress to reducing the exposure, the epidemiological evidence and
      exposure measurement data available. Finally, we illustrate the dispersion in the
      environment as a real risk for the general population.

PMID- 24665623
TI  - [Sleep apnea, CPAP therapy and work activity].
AB  - Obstructive Sleep Apnea syndrome (OSAS) is largely prevalent among the general
      adult population, particularly among obese subjects. Diurnal somnolence is a
      characteristic feature of OSAS, one that can interfere on daily life of the
      patients and also on his/her work-related activities. Aim of this study was to
      evaluate the impact of OSAS, its symptoms and its therapy with Continuous
      Positive Airway Pressure (CPAP) may have on work-related activities. Fourty-eight
      subjects were studied, all > 18 years old and in a work-related age (< 65 years
      for men, < 60 years for women). There were 34 males and 14 females, 38 actively
      working, 3 unemployed, 7 not actively working. Before diagnosis the Epworth
      Sleepiness Scale (ESS) was 12 +/- 4, after the use of CPAP it was 4 +/- 4 (p<
      0.001), the Apnea Hypopnea Index (AHI) before CPAP use was 44 +/- 24, after CPAP
      use 4 +/- 4 (p< 0.001). CPAP compliance was very good (mean hours of CPAP/night 5
      +/- 2). At yearly follow-up, work activity was confirmed in all patients, as all
      employed patients were still working. Our data seem to indicate that not only
      OSAS interferes with working performance, mainly due to OSAS-related diurnal
      somnolence, but also that appropriate CPAP therapy, reinforced with educational
      activities and followed after one year, is able to ameliorate OSAS-related
      symptoms, potential cause of inefficiency an occupational risk at work.

PMID- 24665624
TI  - [Hydrofluoric acid burns of the hands in the home environment: correct
      therapeutic approach].
AB  - The broad market penetration of products with components used primarily in the
      industrial sector requires the precise knowledge of their mechanism of action in
      order to perform a correct therapeutic approach. The article reports on three
      cases of domestic hydrofluoric acid burn that came to our Plastic Surgery Unit
      over the last three years. The treatment options are discussed in detail with
      emphasis on the importance of a constant update about such emerging diseases.

PMID- 24665625
TI  - [A survey of accidents during the clinical rotation of students in a nursing
      degree program].
AB  - Like Registered Nurses, students too should be considered a risk category during
      the period of their clinical training. Their lack of experience and the anxiety
      linked to the first impact with healthcare techniques may lead to accidents. The
      present study aims to investigate the number, the type, the mode, the cause of
      occupational injuries, when and where they happened. It also wants to check the
      level of knowledge of procedures to follow in case of contamination with organic
      material, the reporting of the event, the level of concern felt by the student
      and which of the people he/she turned to were supportive. The survey realized
      through a questionnaire given to 142 undergraduate nursing students at the
      University of Milan, all attending the Fondazione IRCCS Ca' Granda Ospedale
      Maggiore Policlinico, Milan. Out of the 127 who replied to the questionnaire, 32
      had been directly involved in a total of 38 accidents. The figure shows
      percentage (25.2%) stating that the sample of nursing students described arises
      at a lower level of involvement in accidents than reported in the literature for
      similar series. Preventive measures and specific formative interventions should
      be implemented in order to reduce the incidence of accidents involving nursing
      students, especially where cutting devices are used.

PMID- 24665626
TI  - [Evaluation of work-related stress in call-center workers: application of a
      methodology].
AB  - BACKGROUND: Several studies highlighting a correlation between call-center
      working conditions and psychosocial and ergonomic hazards. OBJECTIVES AND
      METHODS: The aim of this study is to provide an operating methodology for the
      risk assessment of work-related stress. The study involved 554 call-centre
      workers employed in three insurance organizations and a mixed work group (worker,
      company and public health representative) for the study management was defined.
      We experimented an objective self-made checklist and then we administered a
      modified version of the OSI (Occupational Stress Indicator) questionnaire. We
      obtained complementary information from the two different data collection
      methods. RESULTS AND CONCLUSIONS: The findings highlight a low level of perceived
      stress and health complaints compared with other studies previously carried out
      mainly in 'outsourcing' call centres: workers don't show stress symptoms without
      adopting coping strategies. Moreover the study underlines an acceptable level of
      work satisfaction, although there are low career opportunities. These results are
      probable due to the low job seniority associated to the high job security--the
      large majority of respondents, 87%, consisted of permanent workers--and the
      working time mainly consisted of daily shifts five days a week. Our methodology
      seems to be able to detect the level of work-related stress with a good degree of
      coherence. Furthermore the presence of a mixed work group determined a good level
      of involvement among the workers: 464 out of 554 operators completed and returned
      the questionnaire, representing a response rate of about 84%.

PMID- 24665628
TI  - [The economics of preventing psycho-social risks].
AB  - PREFACE: The aim of the essay is to show the SHIELD methodology for helping the
      firm management to improve the risks prevention policy. It has been tested in the
      field with positive results. SHIELD is a cost-benefit analysis application to
      compare prevention and non-prevention costs, which arise from non-market risks.
      In the economic perspective safety risks (which include psycho-social risks) are
      non-market ones as they cause injures to workers during the job. SHIELD (Social
      Health Indicators for Economic Labour Decisions), is the original method proposed
      by the author. It is a cost benefits analysis application, which compares safety
      prevention and non-prevention costs. The comparison allow stop management to
      evaluate the efficiency of the current safety prevention policy as it helps top
      management to answer to the policy question: how much to invest in prevention
      costs? The costs comparison is obtained through the reclassification of safety
      costs between prevention and non-prevention costs (which are composed by claim
      damages and penalty sanction costs). RESULTS AND CONCLUSION: SHIELD has been
      tested empirically in four companies operating in the agribusiness sector during
      a research financed by the Assessorato all'Agricoltura and INAI Regionale of
      Emilia Romagna Region. Results are postive: it has been found that the increase
      of prevention costs causes the cut of non-prevention costs in all companies
      looked into, as assumed by the high reliability organization theory. SHIELD can
      be applied to all companies which must have an accounting system by law, no
      matter of the industry they act. Its application has limited costs as SHIELD
      doesn't need changes in the accounting system. Safety costs sustained by the
      company are simply reclassified in prevention and non-prevention costs. The
      comparison of these two costs categories has been appreciated by top management
      of companies investigated as a useful support to decide the risks prevention
      policy for the company. The SHIELD original feature compared with others cost
      benefit analysis application is to compute registered costs in the company
      accounting system.

PMID- 24665627
TI  - [Measuring the perception of caring in patients and in nurses: Italian validation
      of the Caring Behaviors Inventory (CBIta)].
AB  - Caring is a key concept in nursing. A nursing practice based on caring behaviors
      can improve quality outcomes in health care services, such as patient
      satisfaction, and can also improve organizational outcomes, such as turnover
      rates and workers wellbeing. A widely used instrument to measure caring behaviors
      perceptions of both patients and nurses is the Caring Behaviors Inventory (CBI).
      The aim of this study is to validate the Italian translation of the 24 items
      version of the CBI on both patients and nurses samples. Content validity of the
      scale was obtained with forward-backward translation process. The scale was
      filled by 213 patients (response rate 88%) and 178 nurses (response rate 95%) in
      surgical settings and showed high reliability (Cronbach a respectively 0.94 and
      0.92). The CFA showed acceptable fit indexes for the 4-factors model in the
      nurses sample. Moreover high response rates indicates a good level of
      acceptability of the scale by both patients and nurses and this result could
      enable a wide use of this tool for a systematic evaluation of care in clinical
      settings and to deepening predictors of turnover and wellbeing in nurses.

PMID- 24665629
TI  - [A review of measures taken to improve organizational wellbeing in Italy].
AB  - INTRODUCTION: The Italian Decree Law D. Lgs. no. 81 dated 9 April 2008, dealing
      with the implementation of Article 1 of Law No. 123 dated 3 August 2007, on the
      topic of health and safety in the workplace, indicated that work-related stress
      (art. 28, section 1) was to be assessed in accordance with the European Agreement
      of 8 October 2004. It recalled the employer's legal obligation to safeguard
      workers' health and safety, and included psychosocial risk, in order to improve
      their wellbeing at work. The Decree Law specified that when risks had been
      assessed the employer could take all necessary measures, with reference to the
      "good practice", defined in the Law as organizational or procedural solutions
      coherent with current regulations and good technical rules, adopted voluntarily
      with the aim of promoting safety and health in the workplace by reducing risk and
      improving working conditions [...]" (art. 2, section 1 v); the practical
      solutions identified were to aim at eliminating, or at least reducing,
      psychosocial risk in the enterprise. METHOD: On the basis of the studies most
      widely accepted in Europe and the indications issued by the European Agency for
      Safety and Health at Work, we identified the good practice measures adopted by
      companies in Italy and other countries. The aim was to make known some of the
      practical solutions regarding psychosocial risk that companies can put in place
      with a view to improving their workers' health and wellbeing. RESULTS: We
      examined measures related to the content and context of work. Measures affecting
      the work content mainly involved the workplace itself and equipment, work
      planning and working hours. For the work context the measures centered mostly on
      organizational function and culture, career progress, and home/work interface.
      CONCLUSIONS: In accordance with good safety practice, the practical measures
      taken by the enterprises examined cantered on some potentially stressful features
      of work, indicating the growing attention being paid to workers' wellbeing.
      However, organizational wellbeing is a multifaceted concept and the European
      Agency points out that measures taken must cover all the aspects of the work that
      appear particularly critical in risk assessment; from the primary prevention
      viewpoint, this means all the organizational aspects that might affect a person's
      wellbeing. As we become increasingly aware of the problems, and of the measures
      that have proved successful, it is to be hoped that further solutions will be
      identified and developed in organizations.

PMID- 24665630
TI  - [Caries risk assessment in children].
AB  - Caries risk assessment (CRA) involves a combination and analysis of factors
      including individual's age, biological factors, and protective and clinical
      findings. CRA significantly guides pediatric dentists and oral health caregivers
      in their decision-making plan for clinical treatment. The following is an
      introduction on the aspects of harmfulness of childhood caries and CRA for
      children of different ages.

PMID- 24665632
TI  - [Increased invasion ability mechanism of salivary adenoid cystic carcinoma
      through elevated interstitial fluid pressure in vitro].
AB  - OBJECTIVE: Through a simulation of interstitial fluid pressure (IFP), we
      developed an in vitro model to explore the change law of biological
      characteristics of adenoid cystic carcinoma (ACC) under different IFP. METHODS: A
      pressure cooker was refitted into a controllable pressure device. Cultured ACC-2
      cells were subdivided into different groups, namely, negative control (untreated
      ACC-2) and experimental group (stressed for 3, 6, 12, 24 h under pressure of
      7.551, 7.649, 7.747 kPa). CCK-8 and immunofluorescence of Ki67 were used to
      reflect proliferation ability. Transwell chamber assay was performed to observe
      the invasion ability of cells. RESULTS: The proliferation ability was positively
      correlated with treatment time, and the peak value was obtained after the cells
      were subjected to 7.649 kPa of stress for 24 h. The invasion ability of ACC-2
      cells was upregulated under stress. CONCLUSION: We successfully developed an in
      vitro model of IFP and found that high IFP can stimulate cell proliferation
      ability and upregulate invasion ability.

PMID- 24665631
TI  - [Inhibitory effects of high mobility group chromosomal protein N2 on human tongue
      carcinoma transplanted in nude mice].
AB  - OBJECTIVE: To evaluate the inhibitory effect of high mobility group chromosomal
      protein N2 (HMGN2) on human tongue carcinoma tumor in nude mice. METHODS: A
      transplantation tumor model in nude mice was constructed by injecting Tca8113
      cells. After a week, negative control groups, masculine control groups, and HMGN2
      groups were established. Cell culture of the three groups were separately
      injected with washing buffer II, cis-dichlorodiamineplatinum (DDP), and HMGN2
      protein. The tumors were moved after four treatments, and then analyzed by
      hematoxylin-eosin (HE) staining. RESULTS: A transplanted tumor model was
      established successfully. The volumes of HMGN2 groups and masculine control
      groups were smaller than those of the negative groups. Mouse weight did not
      differ among the three groups. Average tumor weight of the negative group was
      (0.38 +/- 0.19)g, that of the HMGN2 group was (0.21 +/- 0.15)g, and that of the
      DDP group was (0.23 +/- 0.16)g. These factors indicated no statistically
      significant difference among the three groups. The tumor inhibitory rate of HMGN2
      group was 45.71%, and that of the positive group was 39.44%. Based on evaluation
      by naked eye, the tumor in the negative group was larger than that in other
      groups. In addition, cell necrosis was observed during HE staining. CONCLUSION:
      HMGN2 could significantly inhibit growth of the transplanted tumor in nude mice.

PMID- 24665633
TI  - [Effect of taper and inserting angle on stability of micro-implants in type II
      bone with three-dimensional finite element].
AB  - OBJECTIVE: To evaluate the effect of taper and inserting angle on stability of
      micro-implants in type II bone and to provide theoretical evidence for clinical
      selection of taper and inserting angle. METHODS: Three-dimensional finite element
      models of type II bone sections and micro-implants were fabricated. They were
      designed using different tapers (diameter between 1.1 to 1.6 mm, taper between 0
      to 0.0625) and different inserting angles ranging from 30 degrees to 90 degrees
      (30 degrees, 45 degrees, 60 degrees, 75 degrees, 90 degrees). Effects on the
      maximum von Mises stresses in mandible and micro-implants, as well as on the
      maximum displacements in micro-implants, were analyzed under an applied 2 N
      horizontal force. RESULTS: The inserting angle had a significant effect on
      stresses and displacements, with lower distribution of stresses and displacements
      occurring at 60 degrees. The effect of the taper was also related to the
      inserting angle. The minimum stresses were 5.013 4 MPa (cortical bone) and
      25.1310 MPa (micro-implant) in model D at 60 degrees. The displacements of micro
      implants were proportional to the taper. CONCLUSION: The inserting angle has a
      significant effect on stability of micro-implants, and the recommended inserting
      angle is 60 degrees. The influence of taper on the stability of micro-implants is
      related to the inserting angle. The micro-implant with 0.0375 taper (maximum
      diameter is 1.6 mm, minimum diameter is 1.3 mm) is more suitable for type II
      bones.

PMID- 24665634
TI  - [Study of the biological characteristics of p75 neurotrophin receptor positive
      tongue squamous cell carcinoma cells].
AB  - OBJECTIVE: To study the biological characteristics of p75 neurotrophin receptor
      positive (p75(NTR+)) tongue squamous cell carcinoma cells which were separated by
      flow cytometry cell sorting. METHODS: To determine the biological characteristics
      of p75(NTR+) cells which were separated from Tca-8113 and Cal-27 tongue squamous
      cell carcinoma cells by flow cytometry cell sorting, including study the capacity
      of cloning, 3-(4,5)-demethylthiazo(z-y1)-3,5-diphenytetrazoliumromide (MTT)
      assay, wound healing assay. p75(NTR+) cells with non-sorted cells were as control
      group. RESULTS: In Tca-8113 and Cal-27 tongue squamous cell carcinoma cell lines,
      the percentage of p75(NTR+) cells were 3.1% and 1.9%. Compared with p75(NTR+)
      cells with non-sorted cells, p75(NTR+) cells possess higher capacity of cloning
      (Tca-8113, P=0.024; Cal-27, P=0.009). The percentage of p75(NTR+) cells of the
      progeny cells generated from monoclonal p75(NTR+) cells decreased to 14.5% (Tca
      8113) and 5.8% (Cal-27) after cultured two weeks. p75(NTR+) cells possessed
      higher proliferation ability and higher metastasis ability than non-sorted cells.
      CONCLUSION: p75(NTR+) cells isolated from tongue squamous cell carcinoma have the
      characteristics of cancer stem cells.

PMID- 24665635
TI  - [Effect of carbon monoxide releasing molecule on experimental periodontitis in
      rats].
AB  - OBJECTIVE: To evaluate the effects of carbon monoxide releasing molecule-2 (CORM
      2) on experimental periodontitis in rats. METHODS: Forty-two Wistar rats were
      divided into three groups. Rats in the normal group (NL group) did not undergo
      any procedure, whereas the other rats were ligatured and treated with saline
      solution (NaCl 0.9%) (LO group) or treated with CORM-2 (10 mg kg(-1) per day) (CO
      group). A 3-0 silk suture was placed around the mandibular first molars. Rats
      were sacrificed after 3, 7, and 10 d. Blood samples were collected from all
      animals for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) analysis. Changes in alveolar bone levels were measured clinically, and
      periodontal tissues were histopathologically examined to assess the infiltration
      of inflammatory cells. RESULTS: Ligature placement increased alveolar bone loss
      and inflammatory cell infiltration in periodontal tissue. Alveolar bone loss in
      CO group was significantly higher than that in NL group, but was lower than that
      in LO group (P<0.05). The ratio of inflammatory cell infiltration in LO group was
      significantly higher than that in CO and NL groups, and that in CO group was
      lower than in LO group (P<0.05). Serum levels of TNF-alpha and IL-1beta in the LO
      group were significantly higher than those in the CO and NL groups, and those in
      CO group were lower than in LO group (P<0.05). CONCLUSION: Systemic
      administration of CORM-2 reduced periodontal inflammation and alveolar bone loss
      in experimental periodontitis in rats.

PMID- 24665636
TI  - [Preparation of sodium alginate-nanohydroxyapatite composite material for bone
      repair and its biocompatibility].
AB  - OBJECTIVE: To prepare sodium alginate-nanohydroxyapatite composite material and
      to explore its feasibility as a bone repair material. METHODS: Sodium alginate
      nanohydroxyapatite composite material was prepared using chemical cross-linking
      and freeze-drying technology. The composite was characterized by X-ray
      diffraction (XRD) and scanning electron microscope (SEM) and its porosity was
      measured by liquid displacement method. The fifth passage of bone marrow stromal
      stem cells (BMSCs) were incubated on the composite material and then growth was
      observed by inverted microscope and SEM. BMSCs were cultured with liquid extracts
      of the material, methyl thiazolyl tetrazolium (MTT) assay was used to calculate
      the relative growth rate (RGR) on 1, 3, 5 d and to evaluate the cytotoxicity.
      Fresh dog blood was added into the liquid extracts to conduct hemolysis test, the
      spectrophotometer was used to determine the optical density (OD) and to calculate
      the hemolysis rate. RESULTS: Sodium alginate-nanohydroxyapatite composite
      material displayed porosity, the porous pore rate was (88.6 +/- 4.5)%. BMSCs
      showed full stretching and vigorous growth under inverted microscope and SEM.
      BMSCs cultured with liquid extracts of the material had good activities. The
      toxicity of composite material was graded as 1. Hemolysis test results showed
      that the hemolysis rate of the composite material was 1.28%, thus meeting the
      requirement of medical biomaterials. CONCLUSION: The composite material
      fabricated in this study has high porosity and good biocompatibility.

PMID- 24665637
TI  - [Effect of arginine dentifrice on remineralization of initial enamel carious
      lesions].
AB  - OBJECTIVE: To evaluate remineralization efficacy of an arginine containing
      dentifrice on initial enamel carious lesions in vitro. METHODS: Human enamel
      blocks with early lesions were prepared and randomly divided into three treatment
      groups: negative control group (distilled and deionized water), positive control
      group (fluoride containing dentifrice and 0.14% sodium monofluorophosphate), and
      test dentifrice group (8.0% arginine and 0.14% sodium monofluorophosphate). The
      lesions were subjected to a pH-cycling regime for 10 days. Surface enamel
      microhardness of the enamel blocks from each group was measured before and after
      pH cycling, and the surface microhardness recovery was calculated. Then,
      specimens were analyzed for enamel fluoride uptake (EFU) through acid etching
      method, after which they were treated in demineralization solution for a 2 h
      period of acid challenge. The other specimens were sectioned and examined through
      polarized light microscopy. RESULTS: In the test dentifrice group, microhardness
      recovery and EFU were significantly higher than those in the negative control and
      positive groups. The test dentifrice group was significantly resistant to the
      acid challenge compared with the other groups. Conspicuous remineralization of
      enamel subsurface lesions was observed under polarized light microscopy among
      samples treated with test dentifrice, whereas the control groups showed no
      significant changes on enamel subsurface lesions. CONCLUSION: This study presents
      the potential superiority of Pro-Argin dentifrice over conventional fluoride
      dentifrice in promoting the remineralization of initial enamel lesions.

PMID- 24665638
TI  - [Investigation of accuracy of premolar length measured by cone beam CT in vivo].
AB  - OBJECTIVE: To investigate the feasibility and accuracy of length measurement of
      in vivo teeth by using cone beam CT (CBCT). METHODS: Before orthodontic
      extraction, 109 vital premolars from 40 participants were scanned by using CBCT
      and reconstructed by using InVivoDental software. Buccal-lingual sectional images
      along the long axis of teeth were then acquired, and the crown, root, and tooth
      length were measured separately. After careful extraction and fixation, the
      corresponding length of the same tooth was measured by using a digital caliper.
      CBCT measurement accuracy was then verified by using physical measurements as
      reference. RESULTS: CBCT and the physical method did not obtain significantly
      different measurements of the root, crown, and tooth length of experimental teeth
      (P=0.790, P=0.621, P=0.657, respectively), and the measurements were found to be
      consistent. The 95% limits of agreement of root, crown, and tooth length were 
      1.10 mm to 1.13 mm, -1.00 mm to 0.96 mm, and -1.00 mm to 1.05 mm, respectively.
      CONCLUSION: The difference between CBCT and the physical method was not
      significant, and good consistency was shown. CBCT could be applied in noninvasive
      measurement of in vivo teeth.

PMID- 24665639
TI  - [Short-term evaluation of clinical effect of bone ring grafting and immediate
      insertion].
AB  - OBJECTIVE: To observe the short-term clinical effectiveness of bone ring graft
      technique and to summarize the key points of related surgical operation to
      provide comprehensive clinical guidelines. METHODS: Fifteen patients with severe
      alveolar bone absorption were selected to receive bone ring grafting and
      immediate dental implant. Final fixed prostheses were cemented five months after
      initial implantation. Cone beam CT scans were conducted on all subjects before
      the procedure, as well as four months post-operation to evaluate alveolar bone
      height and level of bone height and absorption around the implants. Four to six
      months after prosthesis installation, each implant's Jemt classification, gingiva
      attachment, and probing depth (PD) were analyzed. The difference of PD between
      implants and adjacent teeth, as well as the difference of the bone absorption
      between labial and lingual sides, was compared. The survival rate of the bone
      ring and the retention rate of implants were calculated. Complications and
      patient satisfaction were also investigated. RESULTS: Bone graft survival rate
      was 94.4% and dental implantation retention rate was 100% four months post
      operation. Average bone level increase was (6.06 +/- 1.06) mm, average bone
      absorption was (1.33 +/- 0.84) mm, and average bone thickness at the neck of the
      dental implant body was (6.94 +/- 0.73) mm. Approximately 4 to 6 months after
      crown restoration, average bone level increase was (5.62 +/- 1.03) mm, average
      bone absorption was (1.51 +/- 1.02) mm, and average bone thickness at the neck of
      the dental implant body was (6.77 +/- 0.72) mm. The PD around the implant body
      and the adjacent teeth was statistically insignificant. No major post-operative
      complication was observed, restorations were successful, and patient satisfaction
      level was high. CONCLUSION: Bone ring graft technique and immediate dental
      implantation are relatively simple to perform, and these techniques facilitate
      reduction in required treatment time. Short-term effect is reliable and
      satisfactory, whereas long-term outcomes require further follow up and study.

PMID- 24665640
TI  - [Preliminary study of assessment of mental health level among oral tumor patients
      and difference of relevant material basis].
AB  - OBJECTIVE: To investigate the difference in mental health status of oral tumor
      patients and their spouses, and explore the differences on the basis of relevant
      materials. METHODS: Forty patients with oral cancer, eighteen spouses, and thirty
      five patients with oral benign tumor were diagnosed in the West China Hospital of
      Stomatology between December 2011 and August 2012 and assessed with symptom
      checklist-90 (SCL90) (the 5-grade scoring). Participants were assessed
      independently according to their conditions. Blood samples were obtained from the
      participants by syringe on the second admission day. A method was developed to
      determine the concentrations of catecholamine and glucocorticoid in the serum
      using high performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS). RESULTS: The scores for compel, depression and rests in the cancer group
      and benign tumor group were statistically significant (P<0.05). The scores for
      compel, dread and stubborn in the cancer group and their spouses were
      statistically significant (P<0.05). The differences between the total and other
      monomial factor scores were not statistically significant. However, the contents
      of epinephrine, norepinephrine, cortisone and hydrocortisone in the serum, as
      determined by HPLC-MS/MS, were significantly different (P<0.001). CONCLUSION:
      Psychiatric factors do not show a simple factor effect on patients. Symptoms of
      patients may be based on tumorigenesis and developed in small molecules. Further
      research is required.

PMID- 24665641
TI  - [Clinical research on the simultaneous surgical treatment of craniomaxillofacial
      fracture combined with other injuries].
AB  - OBJECTIVE: This study aimed to compare the treatment effects of simultaneous
      surgical treatment and stage operation for patients with craniomaxillofacial
      fracture combined with other injuries. METHODS: Fifty patients with maxillofacial
      fractures combined with other injuries were chosen and divided into simultaneous
      (28 patients) and staging (22 patients) operation groups. In simultaneous
      operation group, maxillofacial fracture reduction, internal fixation, and other
      parts of the surgery were simultaneously operated by relevant departments
      jointly. In the staging operation group, maxillofacial fracture reduction and
      internal fixation were performed after treatment of other injuries. Data on the
      treatment efficacy and associated injuries of the two groups were statistically
      analyzed. RESULTS: In the simultaneous operation group, 26 patients had good
      occluding relation, the maximum mouth opening was (34.5 +/- 3.7) mm, the symmetry
      and shape of hard tissues recovered well, and the bone plate of one patient was
      removed because of internal fixation infection. In the staging operation group,
      14 patients had good occluding relation, the maximum mouth opening was (28.5 +/-
      3.5) mm, the symmetry and shape of hard tissues poorly recovered, and the bone
      plates of 5 patients were removed because of internal fixation infection.
      Statistical significance was determined among occluding relation, maximum mouth
      opening, postoperative complications, and length of stay of the two groups (P<
      0.05). Treatment of the simultaneous operation group was more effective than that
      of the staging operation group. CONCLUSION: When a patient's condition is
      relatively stable, simultaneous surgical treatment of multiple specialties should
      be conducted to treat craniomaxillofacial fracture combined with other injuries.

PMID- 24665642
TI  - [Influential factors affecting the postoperative velopharyngeal function among
      aged cleft palate patients].
AB  - OBJECTIVE: To determine the factors affecting post-operative velopharyngeal
      function of cleft palate patients aged over two years old. METHODS: The data on
      245 patients, including first visit case records and those in the database, were
      searched and recorded. Post-operative velopharyngeal function and clinical
      features, such as cleft ratio, adequate ratio, diagnosis, operative age and
      method, were analyzed retrospectively. RESULTS: Cleft ratio and adequate ratio in
      the velopharyngeal competence (VPC) group were not statistically different from
      those in the velopharyngeal incompetence (VPI) group. The difference in VPC rate
      in different age groups and diagnosis was not significant. The post-operative VPC
      rates under different methods were significantly different. CONCLUSION: The
      current therapeutic schedule for patients younger than two years old is
      inappropriate for patients older than two years old. Cleft ratio is not the main
      factor affecting postoperative velopharygeal function. Sommerlad-Levator Veli
      Palatini reconstructional operation combined with sphincter pharyngoplasty can
      obviously improve the velopharyngeal function of patients aged 2 years old and
      up. This method should be applied in primary palatoplasty.

PMID- 24665643
TI  - [Analysis of imaging findings in jaw bone islands].
AB  - OBJECTIVE: To provide reference data on frequency and distribution of bone
      islands (BIs) and investigate their relationship with age, gender, and
      localization. METHODS: A population who received a pretreatment and at least one
      follow-up panoramic radiograph in the Department of Oral Radiology, West China
      Hospital of Stomatology, Sichuan University, were selected for this retrospective
      study. A sample population of 29,556 patients (12,824 males and 16,732 females)
      with different dental complaints and ages ranging from 8 to 80 years (mean age:
      23.95 years) were included. RESULTS: In the radiographic evaluation, BIs appeared
      as localized, well-defined, non-expansile, radiopaque masses which were round,
      elliptic, or irregular in shape. Their sizes varied from a few millimeters to
      about 2 cm in diameter. A total of 598 radiopacities were detected, and 545
      patients of 29,556 patients (1.84%) had BIs. Among subjects with multiple
      lesions, 49 patients had 2 BIs and 2 patients had 3 BIs. The BIs had immense
      mandibular predilection, with presentation primarily in the premolar/molar
      region. The condition appeared to have no tendencies based on sex. CONCLUSION:
      Recognition of BIs variation is significant in dental examinations.

PMID- 24665644
TI  - [Crown color match of implant-supported zirconia and porcelain-fused-to-metal
      restorations: a spectrophotometric comparison].
AB  - OBJECTIVE: This study aimed to compare the crown color match of implant-supported
      zirconia restorations and porcelain-fused-to-metal (PFM) restorations in the
      anterior maxillary region through spectrophotometric evaluation. METHODS:
      Eighteen patients with 29 implant-supported single crowns in the anterior
      maxillary area were recruited. Eleven of the implant crowns were zirconia
      restorations and 18 were PFM restorations. Color matching of the implant crown
      with contra-lateral/ neighboring tooth at the position of body 1/3 of the crown
      was assessed using a spectrophotometer (SpectroShade) in CIE L* a* b*
      coordinates. Subjective crown color match scores were evaluated. Independent
      sample t test of SPSS 17.0 was used to compare the difference between zirconia
      restoration and PFM restoration. Spearman correlation was used to analyze the
      relationship between the spectrophotometric color difference and the subjective
      crown color match score. Descriptive statistics was used to analyze the
      distribution of color coordinates of natural anterial teeth. RESULTS: The crown
      color of the implant-supported zirconia restorations and PFM restorations were
      both lighter than that of natural teeth (delta L, 4.5 +/- 3.2, 1.0 +/- 2.6). The
      lightness difference induced by zirconia restorations was significantly larger
      than that induced by PFM restorations (P=0.004). The spectrophotometric crown
      color difference (delta E) induced by zirconia restorations (7.0 +/- 2.8) was
      significantly larger than that induced by PFM restorations (4.0 +/- 1.9)
      (P=0.002), and both values were beyond the clinical thresholds (3.7). CONCLUSION:
      The spectrophotometric crown color difference induced by zirconia restorations
      was significantly larger than that induced by PFM restorations. However, they
      were indistinguishable in subjective evaluation.

PMID- 24665645
TI  - [Effects of non-surgical periodontal treatment on clinical response, serum
      inflammatory parameters, and metabolic control of type 2 diabetes patients with
      moderate to severe periodontitis].
AB  - OBJECTIVE: To evaluate the effects of periodontal treatment on the clinical
      response, systemic inflammatory parameters, and metabolic control of type 2
      diabetes patients with moderate to severe periodontitis. METHODS: A total of 56
      patients with mean clinical attachment level (CAL)>3 mm were included in the
      subgroup analysis. A repeated-measures ANOVA (group factor: treatment group and
      control group; time factor: initial visit, 1.5, 3, and 6 months) was used to
      analyze the probing depth (PD), CAL, bleeding on probing (BOP), high-sensitivity
      C-reactive protein (hsCRP), glycated hemoglobin (HbA1c), and fasting plasma
      glucose. RESULTS: Significantly lower PD (F=62.898, P-0.000), CAL (F=51.263, P
      0.000), BOP (F=75.164, P=0.000), hsCRP (F=6.391, P=0.010), HbA1c(F=4.536,
      P=0.011), and fasting plasma glucose level (F= 3.073, P=0.031) were observed
      after therapeutic periodontal improvement. The inter-group differences for PD (t=
      2.050, P=0.045), BOP (t=-4.538, P=0.000), and hsCRP (t=-2.261, P=0.028) were
      statistically significant after therapy. CONCLUSION: Non-surgical periodontal
      treatment can effectively improve periodontal status, circulating inflammatory
      status, and metabolic control of diabetic patients with moderate to severe
      periodontitis.

PMID- 24665646
TI  - [Comparative studies on cariogenic bacteria of the root surface before and after
      post-core crown restoration in aged people].
AB  - OBJECTIVE: To investigate the changes in the quantity of colonizing Streptococcus
      mutans(S. mutans) and Actinomyces on the root surface plaque before and after
      post-core crown restoration of the mandibular first molars in the elderly
      patients. METHODS: A total of 30 elderly patients, each with one post-core crown
      restoration of the mandibular first molar, were randomly chosen to participate in
      the studies. Patients with mandibular first molars with post-core crown
      restoration and those with healthy contralateral mandibular first molars were
      divided into the test and control groups, respectively. Root surface plaques of
      the two groups were collected before tooth preparation, 72 h after preparation,
      one week after preparation, and one month after restoration. S. mutans,
      Actinomyces naeslundii (A. naeslundii) and Actinomyces viscosus (A. viscosus),
      were identified using colony morphology, biochemical techniques, and polymerase
      chain reaction (PCR). Plaque count was measured using microbial colony count.
      RESULTS: The number of S. mutans and A. viscosus and A. naeslundii in the test
      group, which was statistically significant (P<0.05), increased 72 h after
      preparation. The quantities of S. mutans, A. viscosus, and A. naeslundii one week
      after preparation were significantly different (P<0.05). The plaque count of S.
      mutans, A. viscosus, and A. naeslundii in the test group decreased one month
      after restoration (P<0.05). CONCLUSION: The quantities of S. mutans, A. viscosus
      and A. naeslundii increase one week after preparation but decrease one month
      after restoration. The finding suggests that dentists should educate patients
      about plaque control during the early period after tooth preparation.

PMID- 24665647
TI  - [In vitro study evaluating the effect of different subgingival root exposure
      methods and ferrule designs on fracture resistance of residual root].
AB  - OBJECTIVE: To evaluate the effect of different subgingival root exposure methods,
      namely, crown lengthening or forced eruption, and different ferrule lengths on
      fracture resistance of a residual root restored with a carbon fiber post-and-core
      system. METHODS: Fifty-six extracted endodontically-treated mandibular first
      premolars were sectioned 1.0 mm coronal to the buccal cementoenamel junction. All
      the models were divided randomly into seven groups that each consist of eight
      roots. Group A was given non-ferrule as control. Simulated crown lengthening was
      performed for the dentin ferrule design in the cervical tooth structure for
      Groups B, C, and D with a ferrule length of 1.0, 2.0, and 3.0 mm, respectively.
      Simulated forced eruption was performed with a ferrule length of 1.0, 2.0, and
      3.0 mm in the cervical tooth structure for Groups E, F, and G, respectively.
      After restoration with prefabricated carbon fiber post-and-core system, each
      specimen was embedded in a self-cured acrylic resin block from 2.0 mm apical to
      the margins of a cast Ni-Cr alloy crown, then loaded at 150 degrees from the long
      axis in a universal testing machine at a crosshead speed of 1.0 mm min(-1) until
      fracture. Data of failure loads and fracture mode were recorded and analyzed.
      RESULTS: Mean failure loads for Groups A to G were (1.13 +/- 0.15), (1.27 +/-
      0.18), (1.02 +/- 0.11), (1.05 +/- 0.12), (1.63 +/- 0.14), (1.92 +/- 0.19), and
      (1.93 +/- 0.15) kN, respectively. The effects of root exposure method and ferrule
      design differed significantly, and two factors exhibited significant interaction
      (F=33.396, P<0.0001). When the ferrule lengths were the same, fracture loads in
      the simulated forced eruption groups were significantly higher than those of the
      simulated crown lengthening groups (P<0.001). No statistical differences in
      fracture mode were observed among all groups (P=1.00). CONCLUSION: More than 1.0
      mm ferrule placement on the apical crown margin by using forced eruption
      significantly increases fracture resistance.

PMID- 24665648
TI  - [The shRNA-mediated downregulation of protein kinase D-2 enhanced
      chemosensitivity of Tca8113].
AB  - OBJECTIVE: To explore the effect of silencing protein kinase D (PKD)-2 on Tca8113
      cell proliferation, programmed cell death, and chemosensitivity. METHODS: The
      stable cell lines of pkd-2 gene silencing and empty vector plasmid group were
      established. The proliferation and 50% inhibitory concentration (IC50) of shRNA
      mediated Tca8113 chemotherapy drugs were detected through methyl thiazolyl
      tetrazolium assay (MTT). The programmed cell death rate and sensitivity to
      Tca8113 chemotherapy drugs before or after pkd-2 gene silencing were measured
      through flow cytometry. P-glycoprotein (P-gp) expression of pkd-2 silencing cells
      was identified by immunohistochemical methods. RESULTS: Stable cell lines of pkd
      2 gene silencing were established. Compared with parental cells, the
      proliferation of shRNA-mediated Tca8113 was not significantly different, but its
      IC50 was lower. Meanwhile, cell programmed death rate and sensitivity to
      chemotherapeutic drugs of shRNA-mediated Tca8113 significantly increased.
      Compared with wild group Tca8113, a significant decrease in P-gp expression was
      induced by chemotherapy drugs with shRNA-pkd-2 gene silencing. CONCLUSION: The
      pkd-2 gene of shRNA interference silencing Tca8113 promotes programmed cell death
      of Tca8113, reduces the IC50 of the chemotherapy drugs, and significantly
      improves the sensitivity of Tca8113 to chemotherapeutic drugs while reducing the
      expression of P-gp.

PMID- 24665649
TI  - [Selection of optimal length and diameter of mini implant in two different
      forces: a three-dimensional finite element analysis].
AB  - OBJECTIVE: To investigate the effect of different length and diameters on the
      stability of mini implant and to select optimal length and diameter using
      continuous variation of parameters. METHODS: To perform 3-dimensional finite
      element analysis, finite element models of a maxilla, and mini implants with
      length of 6-12 mm and diameters of 1.2-2.0 mm were generated. Load of two
      different forces were applied to the head of mini implant. One type was
      horizontal force (HF), the other was composite force (CF). The maximum equivalent
      stress (Max EQV) in maxilla and the maximum displacement (Max DM) of mini implant
      were evaluated. RESULTS: The Max EQV in maxilla and Max DM of mini implant
      decreased as length and diameter increased. When length was more than 9 mm, the
      evaluation indexes were small and had a less change. Datas indicated that
      diameter played a more important role in reducing target, and was a more
      effective parameter in reducing Max EQV when CF was loaded. CONCLUSION: From
      biomechanical point of view, the choice of the length should not be more than 9
      mm. When CF is loaded using the mini implant, diameter exceeding 1.2 mm are
      optimal design for mini implant.

PMID- 24665650
TI  - [Effects of gossypol acetic acid on the proliferation and methylation level of
      the human MutL homologue 1 gene in human tongue carcinoma cell line Tca8113].
AB  - OBJECTIVE: This paper aims to study the effects of gossypol acetic acid (GAA) on
      proliferation and methylation level of human MutL homologue 1 (hMLH1) gene in
      human tongue cancer cell line Tca8113. METHODS: The MTT assay was used to
      determine the effects of the acid on the proliferation inhibition in Tca8113
      cells treated with different GAA concentrations. Nested methylation-specific
      polymerase chain reaction (nMSP) was used to detect the change in the methylation
      level of hMLH1 after 48 and 72 h with 30 and 15 micro mol L(-1) GAA treatment.
      RESULTS: MTT assay results showed the growth and proliferation inhibition of
      Tca8113 cells in the experimental GAA group after 24 h to 72 h of GAA treatment.
      The nMSP results indicated that the average optical density of hMLH1 in the
      Tca8113 cells significantly changed after the GAA treatment (30 micro mol L(-1)
      GAA for 48 h and 15 micro mol L(-1) for 72 h) (P<0.05) compared with that of the
      control group. CONCLUSION: GAA does not only inhibit Tca8113 proliferation but
      also has a demethylation effect on the hMLH1 gene. These phenomena may be part of
      an underlying tumor-suppression mechanism of GAA.

PMID- 24665651
TI  - [Tongue osteocartilaginous choristoma: a case report].
AB  - Tongue osteocartilaginous choristoma is the disease that there are well-developed
      bone and cartilage in the tongue. This article reported a case of tongue
      osteocartilaginous choristoma in the oral-cavity,which is rare.

PMID- 24665652
TI  - [Inversion of unerupted second deciduous molar and second premolar: a case
      report].
AB  - Impacted teeth are usually involved in permanent dentition but not in primary
      dentition. This paper reports a clinical case of unerupted mandibular second
      deciduous molar inferior to the second premolar.

PMID- 24665653
TI  - [Technology of nitrous oxide/oxygen inhalation sedation and its clinical
      application in pediatric dentistry].
AB  - Dental fear is a common problem in pediatric dentistry. Therefore, sedation for
      pediatric patients is an essential tool for anxiety management. Nitrous
      oxide/oxygen inhalation sedation is a safe, convenient, effective way to calm
      children. The review is about the technology of nitrous oxide/oxygen inhalation
      sedation and its clinical application in pediatric dentistry.

PMID- 24665654
TI  - [New approaches in acute kidney insufficiency and vasculitides ].

PMID- 24665655
TI  - [Epidemiology of community-acquired acute kidney injury].
AB  - Community-acquired acute kidney injury (CA-AKI) is on the rise and is nowadays a
      major public health problem. In the western world, CA-AKI concerns in priority
      elderly patients with multiple comorbidities and treated with nephrotoxic
      medications. Earlier detection of patients at risk and teaching them how to
      prevent CA-AKI will minimize its prevalence and complications.

PMID- 24665656
TI  - [Interpretation of volemia in acute kidney injury].
AB  - Assessment of volume status is often challenging in daily clinical practice. One
      of the clinician's tasks is to prevent or to treat organ systems failures that
      arise from a mismatch between the transport of oxygen and metabolic needs. Renal
      failure is a frequently encountered in-hospital diagnosis that is known to alter
      significantly the prognosis. In patients with acute renal failure in particular,
      the consequences of an inadequate volume management further increase morbidity
      and mortality.

PMID- 24665657
TI  - [Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].
AB  - Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome
      characterized by kidney damage that can lead to irreversible kidney failure. RPG
      can be caused by primary glomerular disease or can be part of a systemic
      autoimmune disorder. All RPG have a similar pathophysiology (proliferation of
      cells in Bowman's capsule and formation of crescents) and clinical evolution
      (rapidly progressive kidney failure with proteinuria and an active urine
      sediment). Immunosuppressive therapy and sometimes plasma exchanges are required.
      Overall- and kidney survival are closely linked to the blood creatinine level at
      presentation, the percentage of damaged glomeruli, and to the underlying cause.
      RPG is therefore a diagnostic and therapeutic emergency that needs quick referral
      to a nephrologist.

PMID- 24665659
TI  - [Renal disease in ANCA-associated vasculitis].
AB  - ANCA-associated vasculitis are systemic disorders characterized by inflammation
      predominantly involving small vessels. They are the most frequent cause of
      rapidly progressive glomerulonephritis in the elderly. They originate from
      complex interactions between genes and environment, resulting in autoimmunity and
      the generation of antibodies directed against neutrophil cytoplasmic antigens
      (ANCA), which may have pathogenic potential. Immunosuppressant agents,
      particularly cyclophosphamide, have considerably improved the prognosis, but
      infectious complications and relapses remain frequent. Recently, rituximab has
      been shown to be a good alternative to cyclophosphamide to induce remission.
      Additional knowledge should result in better clinical outcomes, minimizing side
      effects.

PMID- 24665658
TI  - [Use of antiplatelet agents in patients with chronic kidney disease: what is the
      evidence?].
AB  - Patients with chronic kidney disease are particularly prone to cardiovascular
      disorders because of a tendency to thrombosis, but also have an enhanced
      hemorrhagic risk. The use of antiplatelet agents in this subset of patients is
      not yet well defined and caution should be given on which AAP is prescribed to
      them.

PMID- 24665660
TI  - [Renal risks of dietary complements: a forgotten cause].
AB  - The use of dietary complements like vitamins, minerals, trace elements, proteins,
      aminoacids and plant-derived agents is prevalent in the general population, in
      order to promote health and treat diseases. Dietary complements are considered as
      safe natural products and are easily available without prescription. However,
      these can lead to severe renal toxicity, especially in cases of unknown pre
      existing chronic kidney disease (CKD). In particular, Chinese herbs including
      aristolochic acid, high doses of vitamine C, creatine and protein complements may
      lead to acute and chronic renal failure, sometimes irreversible. Dietary
      complement toxicity should be suspected in any case of unexplained renal
      impairement. In the case of pre-existing CKD, the use of potentially nephrotoxic
      dietary complements should be screened for.

PMID- 24665661
TI  - [Fit to work].

PMID- 24665662
TI  - [Alcoholic intoxication and speed: when ski runs become roads].

PMID- 24665663
TI  - [Can we stop feeding minimally conscious state patients? ].

PMID- 24665664
TI  - [Diary of plague patient---blogger before his time: Samuel Pepsys (1633-1703)].

PMID- 24665666
TI  - The transposition of the Directive on Patients' Rights in Cross-care Healthcare
      in national law by the Member States: still a lot of effort to be made and
      questions to be answered.

PMID- 24665665
TI  - [Personalized medicine and narcissistic future].

PMID- 24665667
TI  - Implementation of the Directive 2011/24/EU in the Czech Republic.
AB  - The article describes implementation of the Directive 2011/24/EU in the Czech
      Republic, its consequences with individual patient's rights and financing of
      healthcare for citizens of the European Union.

PMID- 24665668
TI  - Implementation of the Directive on the Application on Patient's Rights in Cross
      border Healthcare (2011/24/EU) in Finland.
AB  - Implementation of the Directive on the Application on Patient's Rights in Cross
      border Healthcare (2011/24/EU) has proved to be quite challenging in Finland.

PMID- 24665669
TI  - Cross-border healthcare: Directive 2011/24 and the Greek law.
AB  - The Greek legal framework on healthcare is characterized by the complexity of an
      immense number of laws and regulatory acts, particularly regarding the national
      health system. In the face front of that problem, the Directive stands as an
      effort (and an opportunity) to achieve a regulatory rationalization. The Law
      3918/2011 established the National Organisation for Healthcare (EOPYY). EOPYY is
      the unique national contact point in the country for the purposes of the
      Directive, having a responsibility to ensure that the services provided by its
      affiliated healthcare providers meet certain quality and safety standards.
      Furthermore, the Greek legal system encompasses an integrated body of legislation
      on informed consent, privacy, and data protection, as well as an explicit
      reference to the 'quality, safety and efficiency' of medical services, and
      provisions related to reimbursement issues that need further regulatory
      specification.

PMID- 24665670
TI  - Implementation of the Patients' Rights in Cross-border Healthcare directive in
      Latvia.
AB  - Latvia, being one of the EU Member States, has an obligation to implement the
      rules stated by the Directive 2011/24/EU on Patients' Rights in Cross-border
      Healthcare (hereinafter--the Directive) before 25 October 2013 in existing
      national legislation and practice. Implementation was carried out under pressured
      circumstances. A National Contact Point has been established, information is
      provided for patients in Latvian and to some extent in English, the Medical
      Treatment Risk Fund will start operations to provide compensation for harm, and
      the restrictions and procedure for prior authorisation have been stated. The need
      to secure quality of care and patient safety and well as privacy protection are
      the most challenging tasks for Latvia. It can be concluded that some progress in
      patients' rights can be achieved, but it is doubtful if patients' mobility will
      be stimulated.

PMID- 24665671
TI  - Implementation of the Cross-border Care Directive in EU Member States:
      Luxembourg.
AB  - The Cross-border Care Directive sets up basic patient rights in case of cross
      border healthcare. These rights concern both the country of affiliation and the
      country of treatment of the patient. The article briefly describes the state of
      the transposition in Luxembourg, with a focus on the draft act on patients'
      rights and obligations. This new act on patient rights and obligations will apply
      without distinction to domestic and cross-border patients, thus transposing most
      of Luxembourg's obligations as a country of treatment of a cross-border patient.

PMID- 24665672
TI  - The implementation of the Directive on the Application of Patients' Rights in
      Cross-border Healthcare in the Netherlands.
AB  - This article discusses the significance of the Directive 2011/24/EU on the
      application of patients' rights in cross-border healthcare for the protection of
      individual patients' rights in the Netherlands by describing how its provisions
      are implemented in Dutch health law. The responsible Dutch authorities take the
      view that most of the Directive's provisions and requirements are covered in
      existing Dutch law. Implementation of the Directive would only require
      adaptations to national legislation with regard to the establishment of a
      national contact point for cross-border healthcare and the recognition of medical
      prescriptions issued in another Member State. This article looks into the
      question of how far the Dutch law meets the requirements of the Directive in
      relation to the individual patients' rights addressed in this special issue of
      the European Journal of Health Law.

PMID- 24665673
TI  - Cross-border healthcare in Spain and the implementation of the Directive
      2011/24/EU on the Application of Patient's Rights in Cross-border Healthcare.
AB  - This work describes and assesses the implementation of the Cross-border
      Healthcare Directive in Spain. Although implementation has not yet taken place,
      the Government has already adopted a draft implementing regulation, on which this
      article is based. In addition, this article deals with a number of other rules
      that have been adopted in Spain, which are not strictly aimed at the
      implementation of the Directive but which are expected to facilitate its
      implementation and to help cement its effectiveness.

PMID- 24665674
TI  - European Court of Human Rights. ECHR 2014/1 Case of Mircea Dumitrescu v. Romania,
      30 July 2013, no. 14609/10 (Third Section).

PMID- 24665675
TI  - European Court of Human Rights. ECHR 2014/2 Case of H.W v. Germany, 19 September
      2013, no. 17167/11 (Fifth Section).

PMID- 24665676
TI  - European Court of Human Rights. ECHR 2014/3 Case of M.H. v. The United Kingdom,
      22 October 2013, no. 11577/06 (Fourth Section).

PMID- 24665677
TI  - European Court of Justice. ECJ 2014/1, IVD GmbH & Co. KG v. Arztekammer Westfalen
      Lippe, 12 September 2013 (Case C-526/11).

PMID- 24665678
TI  - European Court of Justice. ECJ 2014/2, BKK Mobil Oil Korperschaft des
      offentlichen Rechts v. Zentrale zur Bekampfung unlauteren Wettbewerbs eV, 3
      October 2013 (Case C-59/12).

PMID- 24665680
TI  - Status of Rhagoletis (Diptera: Tephritidae) pests in the NAPPO countries.
AB  - The North American Plant Protection Organization (NAPPO) is an organization
      comprising plant protection regulatory officials of the three signatory
      countries: the United States, Canada, and Mexico. NAPPO develops Regional
      Standards for Phytosanitary Measures (RSPMs) as well as discussion papers on
      important issues related to plant protection. The Fruit Panel of NAPPO organized
      a Technical Assistance Group (TAG) to develop a discussion paper on the status of
      pest species of Rhagoletis (Diptera: Tephritidae) within the NAPPO countries. As
      regulations are developed to prevent the spread of these pests both within and
      outside of the NAPPO countries, it was important to understand the pest status of
      these species. This article reviews the basic biology, host range, distribution,
      potential to spread, management, and regulatory status of pest species of
      Rhagoletis within the NAPPO countries.

PMID- 24665679
TI  - Assessing transmission of crop diseases by insect vectors in a landscape context.
AB  - Theory indicates that landscape composition affects transmission of vector-borne
      crop diseases, but few empirical studies have investigated how landscape
      composition affects plant disease epidemiology. Since 2006, Bemisia tabaci
      (Gennadius) has vectored the cucurbit yellow stunting disorder virus (CYSDV) to
      cantaloupe and honeydew melons (Cucumis melo L.) in the southwestern United
      States and northern Mexico, causing significant reductions in yield of fall
      melons and increased use of insecticides. Here, we show that a landscape-based
      approach allowing simultaneous assessment of impacts of local (i.e., planting
      date) and regional (i.e., landscape composition) factors provides valuable
      insights on how to reduce crop disease risks. Specifically, we found that
      planting fall melon fields early in the growing season, eliminating plants
      germinating from seeds produced by spring melons after harvest, and planting fall
      melon fields away from cotton and spring melon fields may significantly reduce
      the incidence of CYSDV infection in fall melons. Because the largest scale of
      significance of the positive association between abundance of cotton and spring
      melon fields and CYSDV incidence was 1,750 and 3,000 m, respectively, reducing
      areas of cotton and spring melon fields within these distances from fall melon
      fields may decrease CYSDV incidence. Our results indicate that landscape-based
      studies will be fruitful to alleviate limitations imposed on crop production by
      vector-borne diseases.

PMID- 24665681
TI  - Insecticide use in hybrid onion seed production affects pre- and postpollination
      processes.
AB  - Research on threats to pollination service in agro-ecosystems has focused
      primarily on the negative impacts of land use change and agricultural practices
      such as insecticide use on pollinator populations. Insecticide use could also
      affect the pollination process, through nonlethal impacts on pollinator
      attraction and postpollination processes such as pollen viability or pollen tube
      growth. Hybrid onion seed (Allium cepa L., Alliaceae) is an important pollinator
      dependent crop that has suffered yield declines in California, concurrent with
      increased insecticide use. Field studies suggest that insecticide use reduces
      pollination service in this system. We conducted a field experiment manipulating
      insecticide use to examine the impacts of insecticides on 1) pollinator
      attraction, 2) pollen/stigma interactions, and 3) seed set and seed quality.
      Select insecticides had negative impacts on pollinator attraction and
      pollen/stigma interactions, with certain products dramatically reducing pollen
      germination and pollen tube growth. Decreased pollen germination was not
      associated with reduced seed set; however, reduced pollinator attraction was
      associated with lower seed set and seed quality, for one of the two female lines
      examined. Our results highlight the importance of pesticide effects on the
      pollination process. Overuse may lead to yield reductions through impacts on
      pollinator behavior and postpollination processes. Overall, in hybrid onion seed
      production, moderation in insecticide use is advised when controlling onion
      thrips, Thrips tabaci, on commercial fields.

PMID- 24665682
TI  - Crop-emptying rate and the design of pesticide risk assessment schemes in the
      honey bee and wild bees (Hymenoptera: Apidae).
AB  - Recent scientific literature and reports from official sanitary agencies have
      pointed out the deficiency of current pesticide risk assessment processes
      regarding sublethal effects on pollinators. Sublethal effects include troubles in
      learning performance, orientation skills, or mobility, with possible contribution
      to substantial dysfunction at population scale. However, the study of sublethal
      effects is currently limited by considerable knowledge gaps, particularly for the
      numerous pollinators other than the honey bee Apis mellifera L.--the traditional
      model for pesticide risk assessment in pollinators. Here, we propose to use the
      crop-emptying time as a rule of thumb to guide the design of oral exposure
      experiments in the honey bee and wild bees. The administration of contaminated
      sucrose solutions is typically followed by a fasting time lapse to allow complete
      assimilation before the behavioral tests. The fasting duration should at least
      encompass the crop-emptying time, because no absorption takes place in the crop.
      We assessed crop-emptying rate in fasted bees and how it relates 1) with sucrose
      solution concentration in the honey bee and 2) with body mass in wild bees.
      Fasting duration required for complete crop emptying in honey bees fed 20 microl
      of a 50% sucrose solution was nearly 2 h. Actual fasting durations are usually
      shorter in toxicological studies, suggesting incomplete crop emptying, and
      therefore partial assimilation of experimental solutions that could imply
      underestimation of sublethal effects. We also found faster crop-emptying rates in
      large wild bees compared with smaller wild bees, and suggest operative rules to
      adapt sublethal assessment schemes accordingly.

PMID- 24665683
TI  - New methods and media for the centrifugation of honey bee (Hymenoptera: Apidae)
      drone semen.
AB  - Centrifugation of Apis mellifera L. drone semen is a necessary step in the
      homogenization of semen pools for the enlargement of the effective breeding
      population, as well as in the collection of semen by the so-called washing
      technique. It is also of interest for the removal of cryoprotectants after
      cryopreservation. The adoption of methods involving semen centrifugation has been
      hampered by their damaging effect to sperm. Here, we tested four new diluents as
      well as three additives (catalase, hen egg yolk, and a protease inhibitor), using
      sperm motility and dual fluorescent staining as indicators of semen quality.
      Three of the new diluents significantly reduced motility losses after
      centrifugation, as compared with the literature standard. Values of motility and
      propidium iodide negativity obtained with two of these diluents were not
      different from those measured with untreated semen. The least damaging diluent, a
      citrate-HEPES buffer containing trehalose, was then tested in an insemination
      experiment with centrifuged semen. Most queens receiving this semen produced
      normal brood, and the number of sperm reaching the storage organ of the queen was
      not significantly different from that in queens receiving untreated semen. These
      results could improve the acceptance of techniques involving the centrifugation
      of drone semen. The diluent used in the insemination experiment could also serve
      as semen extender for applications not involving centrifugation.

PMID- 24665685
TI  - Potential transmission of Pantoea spp. and Serratia marcescens
      (Enterobacteriales: Enterobacteriaceae) to plants by Lygus hesperus (Hemiptera:
      Miridae).
AB  - Lygus hesperus Knight (Hemiptera: Miridae) is a key agricultural pest in the
      western United States. In a recent study, proteins from Pantoea ananatis and
      Serratia marcescens (Enterobacteriales: Enterobacteriaceae) were identified in
      diet that was stylet probed and fed on by L. hesperus adults. P. ananatis and S.
      marcescens are ubiquitous bacteria that infect a wide range of crops. The
      objective of our study was to determine whether L. hesperus transfer P. ananatis
      and S. marcescens to food substrates during stylet-probing activities. Sucrose
      (5%) was spread under parafilm and exposed to adult L. hesperus for 24 h. Diet
      similarly prepared but not exposed to insects was used for controls. MacConkey
      agar was inoculated with stylet-probed or control diets and incubated at 25
      degrees C. After 24 h, bacterial colonies were observed on agar that was
      inoculated with stylet-probed diet, but were not observed on agar inoculated with
      control diet. Isolated bacterial colonies were putatively identified as either
      Pantoea spp. or S. marcescens using the API 20e identification kit. These results
      indicate that L. hesperus is capable of vectoring P. ananatis and S. marcescens.

PMID- 24665684
TI  - Evaluation of cage designs and feeding regimes for honey bee (Hymenoptera:
      Apidae) laboratory experiments.
AB  - The aim of this study was to improve cage systems for maintaining adult honey bee
      (Apis mellifera L.) workers under in vitro laboratory conditions. To achieve this
      goal, we experimentally evaluated the impact of different cages, developed by
      scientists of the international research network COLOSS (Prevention of honey bee
      COlony LOSSes), on the physiology and survival of honey bees. We identified three
      cages that promoted good survival of honey bees. The bees from cages that
      exhibited greater survival had relatively lower titers of deformed wing virus,
      suggesting that deformed wing virus is a significant marker reflecting stress
      level and health status of the host. We also determined that a leak- and drip
      proof feeder was an integral part of a cage system and a feeder modified from a
      20-ml plastic syringe displayed the best result in providing steady food supply
      to bees. Finally, we also demonstrated that the addition of protein to the bees'
      diet could significantly increase the level ofvitellogenin gene expression and
      improve bees' survival. This international collaborative study represents a
      critical step toward improvement of cage designs and feeding regimes for honey
      bee laboratory experiments.

PMID- 24665686
TI  - Plant water stress effects on stylet probing behaviors of Homalodisca vitripennis
      (Hemiptera: Cicadellidae) associated with acquisition and inoculation of the
      bacterium Xylella fastidiosa.
AB  - ABSTRACT The glassy-winged sharpshooter, Homalodisca vitripennis (Germar)
      (Hemiptera: Cicadellidae), is a xylem fluid-ingesting leafhopper that transmits
      Xylella fastidiosa Wells et al., a plant-infecting bacterium that causes several
      plant diseases in the Americas. Although the role of plant water stress on the
      population density and dispersal ofH. vitripennis has been studied, nothing is
      known about the effects of plant water stress on the transmission of X.
      fastidiosa by H. vitripennis. A laboratory study was conducted to determine the
      influence of plant water stress on the sharpshooter stylet probing behaviors
      associated with the acquisition and inoculation of X. fastidiosa. Electrical
      penetration graph was used to monitor H. vitripennis feeding behaviors for 20-h
      periods on citrus [Citrus sinensis (L.) Osbeck] and almond [Prunus dulcis
      (Miller) D.A. Webb] plants subjected to levels of water stress. Adult H.
      vitripennis successfully located xylem vessels, then performed behaviors related
      to the evaluation of the xylem cell and fluid, and finally ingested xylem fluid
      from citrus and almond plants under the tested fluid tensions ranging from -5.5
      to -33.0 bars and -6.0 to -24.5 bars, respectively. In general, long and frequent
      feeding events associated with the acquisition and inoculation of X. fastidiosa
      were observed only in fully irrigated plants (i.e., >-10 bars), which suggests
      that even low levels of plant water stress may reduce the spread of X.
      fastidiosa. Results provided insights to disease epidemiology and support the
      hypothesis that application of regulated deficit irrigation has the potential to
      reduce the incidence of diseases caused by X.fastidiosa by reducing the number of
      vectors and by decreasing pathogen transmission efficiency.

PMID- 24665687
TI  - Seasonal dynamics of thrips (Thrips tabaci) (Thysanoptera: Thripidae)
      transmitters of iris yellow spot virus: a serious viral pathogen of onion bulb
      and seed crops.
AB  - Thrips-transmitted Iris yellow spot virus (IYSV) is an important economic
      constraint to the production of bulb and seed onion crops in the United States
      and many other parts of the world. Because the virus is exclusively spread by
      thrips, the ability to rapidly detect the virus in thrips vectors would
      facilitate studies on the role of thrips in virus epidemiology, and thus
      formulation of better vector management strategies. Using a polyclonal antiserum
      produced against the recombinant, Escherichia coli-expressed nonstructural
      protein coded by the small (S) RNA of IYSV, an enzyme linked immunosorbent assay
      was developed for detecting IYSV in individual as well as groups of adult thrips.
      The approach enabled estimating the proportion of potential thrips transmitters
      in a large number of field-collected thrips collected from field-grown onion
      plants. Availability of a practical and inexpensive test to identify viruliferous
      thrips would be useful in epidemiological studies to better understand the role
      of thrips vectors in outbreaks of this economically important virus of onion.

PMID- 24665688
TI  - In vivo transmission of 'candidatus Phytoplasma ulmi' by Amplicephalus curtulus
      (Hemiptera: Cicadellidae) and its effect on ryegrass (Lolium multiflorum cv.
      tama).
AB  - In Chile, phytoplasmas have been reported in sugar beet, grapevine, peony, and
      Chilean shrubs. 'Candidatus Phytoplasma ulmi' have been detected in plants of
      Ugni molinae Turczaninow (Myrtaceae) and the leafhopper Amplicephalus curtulus
      Linnavuori & DeLong. We evaluated the possibility of phytoplasma transmission
      from native plants to grasses by A. curtulus and the possible effect on the plant
      hosts. Newly emerged adults were placed in cages with phytoplasma-infected U.
      molinae for 72 h (acquisition access period). These plants were then replaced by
      healthy ryegrasses for 20 d (latent period). They were again replaced for other
      healthy ryegrasses and were place in cages for 14, 7, and 1 d (inoculation access
      period [IAP]). After IAP, these plants were moved into different insect-free
      cages for 30 d, after which polymerase chain reaction (PCR) analyses were carried
      out. Phytoplasma-free insects on ryegrasses were considered as control
      treatments. Furthermore, plant height and leaf area were recorded for all
      treatments. After PCR, 46, 60, and 13% of the plants exposed to infected A.
      curtulus by 14, 7, and 1 d of IAP, respectively, were infected with 'Ca.
      Phytoplasma ulmi'. Similarly, plants exposed to an IAP of 14, 7, and 1 d with
      phytoplasma-infected leafhoppers showed a reduction in plant height of 19, 39,
      and 28% and leaf area of 302, 169, and 55%, respectively, in comparison to those
      exposed to phytoplasma-free leafhoppers. We showed that A. curtulus has the
      ability to transmit phytoplasma from U. molinae to ryegrasses, affecting ryegrass
      plant height and leaf area

PMID- 24665689
TI  - Southern rice black-streaked dwarf virus infection improves host suitability for
      its insect vector, Sogatella furcifera (Hemiptera: Delphacidae).
AB  - The impact of southern rice black-streaked dwarf virus (SRBSDV) on the life cycle
      of the vector Sogatella furcifera (Horvath) (Hemiptera: Delphacidae) was
      investigated. The adult longevity was significantly shorter when the insect was
      reared on the SRBSDV-infected rice plants than those reared on the noninfected
      rice treatment. The fecundity of S. furcifera reared on the SRBSDV-infected rice
      plants was slightly higher than that of those reared on the noninfected rice
      plants both in macropterous and brachypterous cohorts. In addition, SRBSDV
      infection in rice increased the population size of macropterous adults from both
      macropterous and brachypterous cohorts. After a 10 or 15 d feeding period on the
      SRBSDV-infected rice plants, the amount of honeydew excreted by the insect
      increased significantly when compared with those reared on the noninfected
      plants. These results revealed SRBSDV infection improves host suitability for its
      vector, S. furcifera.

PMID- 24665690
TI  - Rapid spread of a recently introduced virus (tomato yellow leaf curl virus) and
      its vector Bemisia tabaci (Hemiptera: Aleyrodidae) in Liaoning Province, China.
AB  - In Liaoning Province, China, tomato yellow leaf curl virus (TYLCV) was first
      detected in 2009 and in only four counties. To quantify the spread of TYLCV and
      to identify potential factors influencing its spread in Liaoning Province, we
      assayed for TYLCV within 1,055 whiteflies (Bemisia tabaci (Gennadius) complex)
      from 74 populations and 29 counties in 2011. The B. tabaci species of these
      individuals was determined based on molecular markers. TYLCV was found in 13
      counties (Donggang, Liaoyang, Kazuo, Lingyuan, Heishan, Liaozhong, Kaiyuan,
      Taian, Dawa, Dashiqiao, Beizhen, Linghai, and Xingcheng) and was most frequently
      detected in the central plain. In addition, the percentage of whiteflies with
      TYLCV was significantly higher in B. tabaci Q than in B. tabaci B but was
      unrelated to the hosts (pepper, eggplant, tomato, cucumber, and kidney bean) on
      which the whiteflies had been collected. These results demonstrate that TYLCV has
      spread rapidly in Liaoning Province since its first detection and suggest that
      its spread is more closely associated with the introduction of B. tabaci Q than
      with the species of host plant. These findings also indicate that controls are
      now needed to reduce the further spread of TYLCV and that these controls should
      include the management of B. tabaci Q populations.

PMID- 24665691
TI  - Natural enemies of Atta vollenweideri (Hymenoptera: Formicidae) leaf-cutter ants
      negatively affected by synthetic pesticides, chlorpyrifos and fipronil.
AB  - In southern South America, Ada vollenweideri Forel (Hymenoptera: Formicidae) is a
      significant pest of several crops and forestry, also considered to reduce the
      carrying capacity of pastures. The most usual control method used in Latin
      America is the application of synthetic pesticides, mainly chlorpyrifos and
      fipronil. However, no studies have assessed the effects of these agrochemicals on
      natural enemies of ants. We aimed to evaluate the efficiency of these pesticides
      on leaf-cutter ants' control and to test their effect on phorid fly parasitoids.
      Chlorpyrifos failed to exert complete control over ant colonies in the field and
      was gravely detrimental to specific parasitoids, reducing their percentage of
      parasitism, pupal survivorship, and adult longevity. Fipronil, however, exerted
      complete control over the treated colonies. Laboratory tests using both
      pesticides, either on ants from foraging trails or on pupariae, showed that
      chlorpyrifos and fipronil decreased larval and pupal survivorship, as well as
      adult longevity of parasitoids, in comparison to controls. In conclusion, these
      pesticides will likely affect parasitoids with regard to their reproductive
      capacity, leading to the decreased levels of natural parasitism observed in the
      field after treatments. We discuss why neither pesticide should be taken into
      account for integrated pest management programs.

PMID- 24665692
TI  - Tri-trophic studies using Cry1Ac-resistant Plutella xylostella demonstrate no
      adverse effects of Cry1Ac on the entomopathogenic nematode, Heterorhabditis
      bacteriophora.
AB  - The potential impacts on natural enemies of crops that produce insecticidal Cry
      proteins from Bacillus thuringiensis (Bt) are an important part of an
      environmental risk assessment. Entomopathogenic nematodes are important natural
      enemies of lepidopteran pests, and the effects of Bt crops on these nontarget
      organisms should be investigated to avoid disruption of their biological control
      function. The objective of this study was to investigate the effects of Cry1Ac
      expressing transgenic Bt broccoli on the entomopathogenic nematode,
      Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae), under tri
      trophic conditions. Using CrylAc-resistant Plutella xylostella L. (Lepidoptera:
      Plutellidae) larvae as hosts, we evaluated the potential impact of Cry1Ac
      expressing Bt broccoli on several fitness parameters of H. bacteriophora.
      Virulence, reproductive potential, time of emergence, and preference of H.
      bacteriophora for the host (P. xylostella) were not significantly affected when
      CrylAc-resistant P. xylostella larvae were reared on leaves of Cry1Ac or non-Bt
      broccoli. Also the aforementioned parameters of the subsequent generation of H.
      bacteriophora did not differ between nematodes obtained from P. xylostella reared
      on CrylAc broccoli compared with those obtained from P. xylostella reared on non
      Bt broccoli. To the best of our knowledge, the current study provides the first
      clear evidence that Cry1Ac does not affect important fitness parameters of H.
      bacteriophora.

PMID- 24665693
TI  - Efficacy of enthomopathogenic fungus Metarhizium anisopliae against Tuta absoluta
      (Lepidoptera: Gelechiidae).
AB  - The tomato borer Tuta absoluta Meyrick is a serious tomato pest that has lately
      undergone a rapid expansion, causing severe crop losses. An integrated management
      is required to control this insect, within which biological control is now
      beginning to play a key role. In this regard, the effectiveness of a liquid
      formulation based on strains of the fungus Metarhizium anisopliae variety
      anisopliae (Metschnikoff) Sorokin (4.46 x 10(9) viable conidia per milliliter),
      applied together with irrigation water, has been evaluated by laboratory tests on
      different populations of T. absoluta. A bioassay method has been developed to
      test the efficacy of the product. The technique chosen has been validated and the
      different studied populations have been typified according to their
      susceptibility, determining the baseline susceptibility of the pest to the
      fungus. The results revealed a complete efficacy of M. anisopliae against pupae
      of T. absoluta at the recommended label rate (5.58 x 10(9) viable conidia per
      liter) for the populations assayed. Moreover, a notably lower dose was also
      sufficiently effective to control the tomato borer populations because values of
      LC90 lower than 3 x 10(9) viable conidia per liter were obtained unfailingly. The
      most sensitive populations were those collected in Almeria and Nijar, Spain, with
      LC50 values of 0.21 and 0.22 x 10(9) viable conidia per liter(-1), respectively.
      The average value obtained for LC50 was 0.34 x 10(9) viable conidia per liter(-1)
      and 2 x 10(9) for LC90. These results show the potential of M. anisopliae to
      control pupae of the tomato borer in integrated pest management programs.

PMID- 24665694
TI  - Host range testing of Tamarixia radiata (Hymenoptera: Eulophidae) sourced from
      the Punjab of Pakistan for classical biological control of Diaphorina citri
      (Hemiptera: Liviidae: Euphyllurinae: Diaphorinini) in California.
AB  - ABSTRACT Tests evaluating the host range of Tamarixia radiata (Waterson)
      (Hymenoptera: Eulophidae), a parasitoid of the pestiferous Asian citrus psyllid,
      Diaphorina citri Kuwayama (Hemiptera: Liviidae), sourced from the Punjab of
      Pakistan, were conducted in quarantine at the University of California,
      Riverside, CA. Seven nontarget psyllid species (five native and two self
      introduced species) representing five families were exposed to T radiata under
      the following three different exposure scenarios: 1) sequential no-choice tests,
      2) static no-choice tests, and 3) choice tests. Nontarget species were selected
      for testing based on the following criteria: 1) taxonomic relatedness to the
      target, D. citri; 2) native psyllids inhabiting native host plants related to
      citrus that could release volatiles attractive to T. radiata; 3) native psyllids
      with a high probability of occurrence in native vegetation surrounding commercial
      citrus groves that could be encountered by T. radiata emigrating from D. citri
      infested citrus orchards; 4) a common native pest psyllid species; and 5) a
      beneficial psyllid attacking a noxious weed. The results of host range testing
      were unambiguous; T radiata exhibited a narrow host range and high host
      specificity, with just one species of nontarget psyllid, the abundant native pest
      Bactericera cockerelli Sulc, being parasitized at low levels (< 5%). These
      results suggest that the likelihood of significant nontarget impacts is low, and
      the establishment of T. radiata in southern California for the classical
      biological control of D. citri poses negligible environmental risk.

PMID- 24665695
TI  - Use of spent mushroom substrate for production of Bacillus thuringiensis by solid
      state fermentation.
AB  - The aim of this study was to explore a cost-effective method for the mass
      production of Bacillus thuringiensis (Bt) by solid-state fermentation. As a
      locally available agroindustrial byproduct, spent mushroom substrate (SMS) was
      used as raw material for Bt cultivation, and four combinations of SMS-based media
      were designed. Fermentation conditions were optimized on the best medium and the
      optimal conditions were determined as follows: temperature 32 degrees C, initial
      pH value 6, moisture content 50%, the ratio of sieved material to initial
      material 1:3, and inoculum volume 0.5 ml. Large scale production of B.
      thuringiensis subsp. israelensis (Bti) LLP29 was conducted on the optimal medium
      at optimal conditions. High toxicity (1,487 international toxic units/milligram)
      and long larvicidal persistence of the product were observed in the study, which
      illustrated that SMS-based solid-state fermentation medium was efficient and
      economical for large scale industrial production of Bt-based biopesticides. The
      cost of production of 1 kg of Bt was approximately US$0.075.

PMID- 24665696
TI  - Bioactivity of Piper hispidinervum (Piperales: Piperaceae) and Syzygium
      aromaticum (Myrtales: Myrtaceae) oils, with or without formulated Bta on the
      biology and immunology of Spodoptera frugiperda (Lepidoptera: Noctuidae).
AB  - The combination of essential oils and Bacillus thuringiensis Berliner may
      represent an interesting control strategy. Thus, the study tested the following
      hypothesis: the combination of long pepper oil (Piper hispidinervum L.) and clove
      (Syzygium aromaticum L.) oils in two concentrations with Xentari WG (Bta) yields
      a more effective control of Spodoptera frugiperda (JE Smith) (Lepidoptera:
      Noctuidae) affecting biological and reproductive parameters and leading to
      changes in the levels of phenoloxidase and nitric oxide in the hemolymph of the
      pest. The results demonstrate that only long pepper oil, at the highest
      concentration with Xentari WG (Bta), promotes reduced larval survival. However,
      both oils with or without the insecticide interfere in the biology and humoral
      immunity of S.frugiperda. All treatments caused a decrease in the amount of eggs,
      except for the clove oil at both concentrations without Bta. Therefore, the use
      of these oils is a promising alternative for the integrated management of S.
      frugiperda; however, its association with Bta demonstrated no significant
      increase in their efficiency.

PMID- 24665697
TI  - The potential of irradiation as a postharvest disinfestation treatment against
      Phlyctinus callosus (Coleoptera: Curculionidae).
AB  - Phlyctinus callosus (Boheman) (Coleoptera: Curculionidae) is a pest of major
      phytosanitary concern for some of South Africa's biggest export markets such as
      the United States and Europe because this pest does not occur there. At present,
      fumigation with methyl bromide is the only postharvest disinfestation treatment
      against this pest; therefore, sustainable alternatives are needed. One such
      alternative is irradiation treatment of whole pallets of packed fruit to
      sterilize insects that may be present within the cartons. Wild adult P. callosus
      weevils were treated with 5, 10, 20, 40, and 80 Gy of gamma-irradiation and then
      cross mated to breed with either treated or nontreated adults of the opposite
      sex. Fecundity and fertility were monitored and recorded. Trials were conducted
      during the 2009-2010 and 2010-2011 fruit harvesting seasons. The results from
      both seasons indicated that irradiation did not affect fecundity but fertility
      was significantly affected, decreasing as irradiation doses increased. Egg hatch
      was zero for mating crosses that involved females weevils treated with a dose of
      80 Gy gamma-irradiation. Probit analysis indicated that in the first season, the
      estimated LD95 for crosses involving treated males and treated females was 30 Gy,
      while in the second season it was 49.5 Gy. Respective estimated LD99S were 47.9
      and 169.4 Gy. Ultimately, a dose lower than the current generic dose of 400 Gy,
      approved for irradiation disinfestation treatments, would control P. callosus
      should they occur in packed export fruit.

PMID- 24665698
TI  - Large-scale confirmatory tests of a phytosanitary irradiation treatment against
      Sternochetus frigidus (Coleoptera: Curculionidae) in Philippine mango.
AB  - The mango pulp weevil, Sternochetus frigidus (F.), is an important quarantine
      pest preventing the export of mangoes from the Philippines to the United States
      and other countries. Previously, a radiation dose of 100 Gy was proposed for
      phytosanitary treatment of S. frigidus based on dose-response studies with
      larvae, pupae, and adult weevils. To validate an irradiation treatment, large
      scale confirmatory tests were conducted with adults (the most radiation-tolerant
      stage) in mangoes at 100 and 150 Gy. After treatment, adults were removed from
      fruit, sexed, and mated in pairs to observe any reproduction. At 100 Gy, adults
      laid a small number of eggs but none of the eggs hatched. At 150 Gy (measured
      doses 96.7-164.1 Gy),4,559 treated weevils laid no eggs, indicating that this
      dose caused complete sterility. Irradiation treatment with a minimum absorbed
      dose of 165 Gy will therefore provide quarantine security for S. frigidus in
      exported Philippine mangoes.

PMID- 24665699
TI  - Life history parameters of Chinavia hilaris (Hemiptera: Pentatomidae), a stink
      bug injurious to pistachios in California.
AB  - Life history parameters were established under controlled laboratory conditions
      for the green stink bug, Chinavia hilaris (Say) (= Acrosternum hilare), to
      improve pest control in pistachios in California. Parameters measured and
      calculated included survival and development at seven constant temperatures
      (ranging from 15 to 35 degrees C), development time, upper and lower development
      thresholds, thermal constants, fecundity, generation time, net reproductive rate,
      and intrinsic rate of increase. C. hilaris did not complete development at 15 and
      35 degrees C. Within the range of 20-27.5 degrees C, development time decreased
      linearly with temperature; it increased again at 30 degrees C. The lower
      threshold was calculated by linear methods to be 12.3 degrees C, and the thermal
      constant was calculated to be 588 degree days. Fastest development was recorded
      at 27.5 degrees C, whereas greatest survival was observed at 22.5 degrees C. At
      27.5 degrees C, mean fecundity was 53.5 eggs per female, mean generation time was
      74.4 d, net reproductive rate was 20.09, and intrinsic rate of increase was 0.04.
      Use of a nonlinear model yielded estimates of 13.2, 28.4, and 33.4 degrees C, for
      the lower threshold, optimum temperature, and upper threshold, respectively.
      Results were compared with similar studies and interpreted in the light of pest
      management needs in pistachio. Increased emphasis on monitoring and management
      ofoverwintering sites and early-season migration are recommended.

PMID- 24665700
TI  - Efficacy of heat treatment for the thousand cankers disease vector and pathogen
      in small black walnut logs.
AB  - Thousand cankers disease, caused by the walnut twig beetle (Pityophthorus
      juglandis Blackman) and an associated fungal pathogen (Geosmithia morbida M.
      Kolarik, E. Freeland, C. Utley, and N. Tisserat), threatens the health and
      commercial use of eastern black walnut (Juglans nigra L.), one of the most
      economically valuable tree species in the United States. Effective phytosanitary
      measures are needed to reduce the possibility of spreading this insect and
      pathogen through wood movement. This study evaluated the efficacy of heat
      treatments and debarking to eliminate P. juglandis and C. morbida in J. nigra
      logs 4-18 cm in diameter and 30 cm in length. Infested logs were steam heated
      until various outer sapwood temperatures (60, 65, and 70 degrees C in 2011; 36,
      42, 48, 52, and 56 degrees C in 2012) were maintained or exceeded for 30-40 min.
      In 2011, all heat treatments eliminated G. morbida from the bark, but logs were
      insufficiently colonized by P. juglandis to draw conclusions about treatment
      effects on the beetle. Debarking did not ensure elimination of the pathogen from
      the sapwood surface. In 2012, there was a negative effect of increasing
      temperature on P. juglandis emergence and G. morbida recovery. G. morbida did not
      survive in logs exposed to treatments in which minimum temperatures were 48
      degrees C or higher, and mean P. juglandis emergence decreased steadily to zero
      as treatment minimum temperature increased from 36 to 52 degrees C. A minimum
      outer sapwood temperature of 56 degrees C maintained for 40 min is effective for
      eliminating the thousand cankers disease vector and pathogen from walnut logs,
      and the current heat treatment schedule for the emerald ash borer (60 degrees C
      core temperature for 60 min) is more than adequate for treating P. juglandis and
      G. morbida in walnut firewood.

PMID- 24665701
TI  - Low-oxygen atmospheric treatment improves the performance of irradiation
      sterilized male cactus moths used in SIT.
AB  - As part of sterile insect technique (SIT) programs, irradiation can effectively
      induce sterility in insects by damaging genomic DNA. However, irradiation also
      induces other off-target side effects that reduce the quality and performance of
      sterilized males. Thus, treatments that reduce off-target effects of irradiation
      on male performance while maintaining sterility can improve the feasibility and
      economy of SIT programs. Exposure to ionizing radiation induces the formation of
      damaging free radicals in biological systems that may reduce sterile male
      performance. Here, we test whether exposure to an anoxic environment for 1 h
      before and during irradiation improves male performance, while maintaining
      sterility in males of the cactus moth, Cactoblastis cactorum (Berg). We show that
      exposure to 1 h of anoxia increases the moth's antioxidant capacity and that
      irradiation in anoxia after 1 h of anoxic conditioning decreases irradiation
      induced oxidative damage to the moth's lipids and proteins. Anoxia treatment that
      reduced oxidative damage after irradiation also produced moths with greater
      flight performance, mating success, and longevity, while maintaining F1 male
      sterility at acceptable levels for SIT. We conclude that anoxia pretreatment
      followed by irradiation in anoxia is an efficient way to improve the quality of
      irradiated moths and perhaps lower the number of moths needed for release SIT
      moth operations.

PMID- 24665702
TI  - Efficacy of commercial traps and food odor attractants for mass trapping of
      Anastrepha ludens (Diptera: Tephritidae).
AB  - One of the most important factors for the success of a mass trapping strategy to
      control a fruit fly involves the selection of an effective trap-lure combination.
      Because different species of fruit flies respond differently to the physical
      characteristics of a trap and to bait volatiles, the evaluation of commercial
      traps and lures that have proved useful against other tephtrids is necessary to
      determine their efficacy for mass trapping of Anastrepha ludens (Loew) (Diptera:
      Tephritidae). Under caged conditions, a commercial hemispherical trap with
      lateral holes (Maxitrap Plus) proved more attractive to A. ludens (both sexes)
      than five other commercial traps that were all baited with hydrolyzed protein.
      Among these traps, bottom invaginated traps and traps with invaginated lateral
      holes constructed with transparent cylinders had the best physical retention
      properties. When evaluated under field conditions, the lure was critical for the
      efficacy of the trap, and one of the traps that performed poorly in attraction
      and retention cage tests (MS2) resulted as one of the most effective traps when
      baited with CeraTrap lure. Considering the use of different trap models under
      field conditions, CeraTrap liquid bait was more effective in A. ludens capture
      than Biolure dry synthetic bait, but both lures were not replaced during the
      entire course of the experiment. The percentage of captured females was also
      slightly higher using CeraTrap lure (67.2%) than using Biolure baits (54.5
      58.8%). In field tests, 75-81% of females were mated and no significant
      differences were observed among trap-lure combinations. Trap selectivity against
      nontarget adult lacewings also differed among trap-lure combinations.

PMID- 24665703
TI  - Evaluation of a method to quantify glassy-winged sharpshooter (Hemiptera:
      Cicadellidae) egg maturation during a feeding assay.
AB  - A method to improve an assay relating adult feeding to egg maturation by the
      glassy-winged sharpshooter (Hemiptera: Cicadellidae) was evaluated. The assay
      consisted on confining females to cowpea stems and quantifying feeding and egg
      maturation. Feeding was quantified by measuring excreta production. The number of
      eggs matured during the assay was estimated by taking the difference between
      female egg load (number of mature eggs carried by a female) at end of the assay
      (determined by dissection) and mean egg load of a subset of females dissected at
      start of the assay. Estimates of the number of mature eggs produced by females
      using the aforementioned approach improve as variability in egg loads of females
      entering the assay declines. As egg loads of females are variable, a pretreatment
      designed to reduce variance in egg loads of females entering the assay was
      evaluated. To accomplish this, females were divided into two groups. The control
      group was placed directly into the assay. The pretreatment group was given an
      oviposition period on sorghum before the assay. An oviposition period on sorghum
      was expected to reduce variance in egg load among females, as previous research
      found that sorghum was suitable for oviposition but provided poor nutrition for
      egg maturation. Dissection of a subset of females from each group before the
      assay determined that the mean and variance in egg load of females receiving the
      pretreatment was significantly reduced compared with females in the control
      group. Analysis of results from the feeding assay found that there was a
      significant relationship between feeding and egg maturation for females receiving
      the pretreatment, but not for females in the control group. Thus, reducing the
      mean and variance in egg load of females entering feeding assays resulted in
      detection of a significant positive relationship between feeding and egg
      maturation that otherwise would not have been observed.

PMID- 24665704
TI  - Evaluation of insecticides for the control of Linepithema (Hymenoptera:
      Formicidae).
AB  - Linepithema micans (Forel) (Hymenoptera: Formicidae) is the main ant species
      responsible for the spreading of Eurhizococcus brasiliensis (Wille) (Hemiptera:
      Margarodidae), a soil scale that damages grapevine plants in southern Brazil. The
      effect of contact and ingestion of insecticides on the control of L. micans was
      evaluated in a greenhouse using grapevines (Vitis spp.) infested by L. micans.
      The insecticides thiamethoxam (250, 187.5, and 125 g/ha), fipronil (4, 5, and 50
      ml/ha), and imidacloprid (650 g/ha) were sprayed on the ground, whereas toxic
      baits containing boric acid (0.5, 1.0, and 1.2%), pyriproxyfen (0.3 and 0.5%),
      and hydramethylnon (0.5%) were evaluated in different formulations.
      Hydramethylnon (toxic bait) and thiamethoxam (chemical barrier) were the most
      efficient active ingredients for the control of L. micans.

PMID- 24665705
TI  - Accumulation and excretion of cadmium in three successive generations of
      Spodoptera exigua (Lepidoptera: Noctuidae) and impact on the population increase.
AB  - Nowadays, heavy metal pollution has become more and more serious. Cadmium is one
      of the heavy metals that have caused serious pollution. Spodoptera exigua Hubner
      (Lepidoptera: Noctuidae), one of important agricultural pests, has broken out
      more frequently in recent years. In this study, accumulation at different
      developmental stages and excretion of Cd were detected, and effect of cadmium (Cd
      concentrations were 0.2, 0.8, 3.2, 12.8, and 51.2 mg/kg, respectively) on three
      successive generations of beet armyworm was also studied using life table in the
      laboratory. Results showed that Cd2+ contents were significantly different when
      S. exigua was reared under different Cd2+ concentrations in the same generation
      in a significant dose-dependent manner. The concentration of Cd2+ increased with
      extension of stress time. Cd2+ concentration at different developmental stages
      was different, that is, larvae > pupa > adult. After emergence, Cd2+
      concentration in both females and males decreased gradually, but that in paired
      adults decreased to a greater extent than that in unpaired ones. Beet armyworm
      could excrete heavy metals by means of faeces, prepupa exuviate, and puparium.
      Life table of the laboratory population was constructed, which showed that low
      doses of cadmium promoted the increase of population, whereas high doses
      inhibited the increase, meanwhile, with the extension of exposure length, the
      index of population trend (I) declined more rapidly. The study might provide
      references for the long-term and objective assessment of heavy metal pollution
      and its effect on the populations of important agricultural pests.

PMID- 24665706
TI  - Soil application of an encapsulated CO2 source and its potential for management
      of western corn rootworm larvae.
AB  - Western corn rootworm (Diabrotica virgifera virgifera LeConte) larvae use carbon
      dioxide (CO2) to locate the roots of their hosts. This study investigated whether
      an encapsulated CO2 source (CO2-emitting capsules) is able to outcompete CO2
      gradients established by corn root respiration in the soil. Furthermore, the
      following two management options with the capsules were tested in semifield
      experiments (0.5- to 1-m2 greenhouse plots): the disruption of host location and
      an "attract-and-kill" strategy in which larvae were lured to a soil insecticide
      (Tefluthrin) between the corn rows. The attract-and-kill strategy was compared
      with an application of Tefluthrin in the corn rows (conventional treatment) at 33
      and 18% of the standard field application rate. Application of the CO2-emitting
      capsules 30 cm from the plant base increased CO2 levels near the application
      point for up to 20 d with a peak at day 10. Both the disruption of host location
      and an attract-and-kill strategy caused a slight but nonsignificant reduction in
      larval densities. The disruption of host location caused a 17% reduction in
      larval densities, whereas an attract-and-kill strategy with Tefluthrin added at
      33 and 18% of the standard application rate caused a 24 and 27% reduction in
      larval densities, respectively. As presently formulated, the CO2-emitting
      capsules, either with or without insecticide, do not provide adequate control of
      western corn rootworm.

PMID- 24665707
TI  - Infestation of grain fields and degree-day phenology of the cereal leaf beetle
      (Coleoptera: Chrysomelidae) in Utah: long-term patterns.
AB  - Scouting at key times in the seasonal development of insect pest populations, as
      guided by degree-day accumulation, is important for minimizing unwarranted
      insecticide application. Fields of small grains in northern Utah were censused
      weekly from 2001 to 2011, to assess infestation by the cereal leaf beetle, Oulema
      melanopus (L.) (Coleoptera: Chrysomelidae), and develop degree-day guidelines for
      measuring cereal leaf beetle abundance at peak egg and larval densities in any
      given year. Even in years of high overall numbers of cereal leaf beetle,
      relatively few fields were heavily infested (with 20 or more cereal leaf beetle
      eggs + larvae per 0.09 m2) at either egg or larval peak density during the
      growing season. In individual fields, the number of immature cereal leaf beetle
      (eggs + larvae) at peak larval density was positively related to the number of
      immature cereal leaf beetles present earlier at peak egg density. Although there
      was large variation among years in when cereal leaf beetle egg and larval numbers
      peaked during the season as measured by degree-day accumulation from 1 January,
      much of this variation was accounted for by the warmth of the early spring before
      significant egg laying occurred. Hence, degree-day estimates that account for
      early spring warmth can guide growers in scouting grain fields at peak egg
      densities to identify fields at high risk of subsequent economic damage from
      cereal leaf beetle larval feeding. The relatively low incidence of fields heavily
      infested by cereal leaf beetle in northern Utah emphasizes the benefit that
      growers can gain by scouting early before applying insecticide treatments.

PMID- 24665708
TI  - Impacts of trunk and soil injections of low rates of imidacloprid on hemlock
      woolly adelgid (Hemiptera: Adelgidae) and eastern hemlock (Pinales: Pinaceae)
      health.
AB  - Eastern hemlocks (Tsuga canadensis Carriere) at two sites in southwestern
      Virginia were treated by trunk and soil injections of imidacloprid to determine
      the insecticide's impact on hemlock woolly adelgid, Adelges tsugae Annand.
      Treatments were 25, 50, and 100% of the highest labeled dosage rates for both
      stem and soil injection. Three and 4 yr after treatment, the half and full rates
      had significantly reduced A. tsugae populations, which were accompanied by
      increased new hemlock shoot growth and higher hemlock health scores on a visual
      rating of tree appearance. Imidacloprid and metabolite concentrations in tissue
      of treated trees were determined by liquid chromatography-tandem mass
      spectrometry, and A. tsugae density decreased as imidacloprid concentrations
      increased in wood tissue. There were no observed A. tsugae populations in all
      trees with imidacloprid tissue concentrations >413 ppb. Olefin, di-hydroxy, and 6
      chloro-nicotinic-acid metabolites were the imidacloprid metabolites recovered in
      the highest concentrations. This suggests that hemlock metabolism of imidacloprid
      may increase efficacy of the parent compound. Stem and soil treatments of low
      rates of systemic imidacloprid reduce adelgid populations and promote hemlock
      health, but still may provide a remnant food source for beneficial predators.

PMID- 24665709
TI  - Generic lures attract cerambycid beetles in a tropical montane rain forest in
      southern China.
AB  - The attraction of cerambycid beetles to 10 known cerambycid pheromones was tested
      in a tropical montane rain forest in southern China. From 28 May to 25 June 2010,
      1,526 cerambycids representing 71 species were captured in pheromone-baited
      traps, with 14 species accounting for 92% of the specimens. Test compounds with a
      3-hydroxyalkan-2-one or 2,3-alkanediol motif attracted significant numbers of
      both sexes for eight species in the subfamily Cerambycinae, including species of
      Demonax, Rhaphuma, and Xylotrechus. Rhaphuma horsfieldi (White) was the only
      species that was strongly attracted to more than one test compound, with
      significant attraction to both (2R*,3R*)-2,3-hexanediol and (2R*,3R*)-2,3
      octanediol. Within the Lamiinae, males and females of five species were
      significantly attracted to 2-(undecyloxy) ethanol, including Acalolepta formosana
      (Breuning), Monochamus bimaculatus Gahan, Pharsalia subgemmata (Thomson),
      Pseudomacrochenus antennatus (Gahan), and Xenohammus bimaculatus Schwarzer. Only
      male Megopis costipennis White (Prioninae) were significantly attracted to
      (2R*,3S*)-2,3-octanediol, suggesting that this compound may be a sex pheromone
      component for this species. To date, 2,3-octanediols have only been reported as
      aggregation pheromone components for cerambycids in the subfamily Cerambycinae.
      Our results support the hypothesis that both closely related (congeners) and more
      distantly related cerambycid species (different tribes and even subfamilies) may
      share pheromone components. Our results also demonstrate that traps baited with
      even a limited number of different classes of pheromones may be useful tools for
      surveying cerambycid diversity, as well as for detecting and monitoring
      particular species, especially those that have the potential to be invasive pests
      in other parts of the world.

PMID- 24665710
TI  - Host selection and probing behavior of the poplar aphid Chaitophorus leucomelas
      (Sternorrhyncha: Aphididae) on two poplar hybrids with contrasting susceptibility
      to aphids.
AB  - Poplars are frequently attacked by aphids. The differential susceptibility of
      poplar hybrids to the aphid Chaitophorus leucomelas Koch (Sternorrhyncha:
      Aphididae) has been described, but the mechanism underlying this pattern is
      unknown. This work tested the hypothesis that poplar resistance to this aphid is
      associated with the presence of volatiles and secondary plant compounds that
      affect host selection and feeding behavior. This hypothesis was tested by
      studying the host choice and feeding behavior of C. leucomelas on two poplar
      hybrids with contrasting susceptibilities to this aphid ([Populus trichocarpa
      Torrey & Gray x Populus deltoides Bartram ex Marshall] x P. deltoides [TD x D],
      and [P. trichocarpa x Populus maximowiczii Henry] x [P. trichocarpa x P.
      maximowiczii] [TM x TM]). The results showed that C. leucomelas rejected leaves
      of the TM x TM hybrid and did not prefer odors from either hybrid. Electronic
      monitoring of the probing behavior of C. leucomelas suggested the involvement of
      antifeedant factors in the TM x TM hybrid. In addition, the chemical
      characterization of volatiles, epicuticular waxes, and internal phenols of leaves
      from both poplar hybrids revealed that TM x TM had a higher abundance of
      monoterpenes, sesquiterpenes, n-alkanes, and phenols. These results are discussed
      in terms of their contribution to poplar breeding programs aimed at enhancing
      insect resistance.

PMID- 24665711
TI  - Relative toxicity and residual activity of insecticides used in blueberry pest
      management: mortality of natural enemies.
AB  - A series of bioassays were conducted to determine the relative toxicities and
      residual activities of insecticides labeled for use in blueberry (Vaccinium
      corymbosum L.) on natural enemies, to identify products with low toxicity or
      short duration effects on biological control agents. In total, 14 insecticides
      were evaluated using treated petri dishes and four commercially available natural
      enemies (Aphidius colemani Viereck, Orius insidiosus [Say], Chrysoperla
      rufilabris [Burmeister], and Hippodamia convergens [Guerin-Meneville]). Dishes
      were aged under greenhouse conditions for 0, 3, 7, or 14 d before introducing
      insects to test residual activity. Acute effects (combined mortality and
      knockdown) varied by insecticide, residue age, and natural enemy species. Broad
      spectrum insecticides caused high mortality to all biocontrol agents, whereas
      products approved for use in organic agriculture had little effect. The reduced
      risk insecticide acetamiprid consistently caused significant acute effects, even
      after aging for 14 d. Methoxyfenozide, novaluron, and chlorantraniliprole, which
      also are classified as reduced-risk insecticides, had low toxicity, and along
      with the organic products could be compatible with biological control. This study
      provides information to guide blueberry growers in their selection of
      insecticides. Further research will be needed to determine whether adoption of a
      pest management program based on the use of more selective insecticides will
      result in higher levels of biological control in blueberry.

PMID- 24665712
TI  - Fumigant toxicity of summer savory and lemon balm oil constituents and efficacy
      of spray formulations containing the oils to B- and neonicotinoid-resistant Q
      biotypes of Bemisia tabaci (Homoptera: Aleyrodidae).
AB  - An assessment was made of the fumigant toxicity of 36 constituents from lemon
      balm oil (LBO) and summer savory oil (SSO) and another additional nine previously
      identified compounds of the oils, as well as of the control efficacy of four
      experimental spray formulations containing individual oils (0.5 and 0.1% sprays)
      and spinosad 10% suspension concentrate (SC) to females from B- and neonicotinoid
      resistant Q-biotypes of Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae).
      Based on 24-h LC50 values, Q-biotype females (0.20 microg/cm3) were 40 times less
      susceptible to dichlorvos than B-biotype females (0.005 microg/cm3). Thymol
      (LC50, 0.35 microg/cm3) and carvacrol (0.56 microg/cm3) were the most toxic
      compounds toward Q-biotype females, followed by (1S)-(-)-borneol, alpha
      terpineol, nerol, linalool, and carvone (1.06-1.38 microg/cm3). The toxicity of
      these compounds was virtually identical toward both biotype females, indicating
      that the terpenoids and the insecticides (neonicotinoids and dichlorvos) do not
      share a common mode of action or elicit cross-resistance. The 0.5% spray of LBO,
      SSO, and spinosad 10% SC resulted in >90% mortality toward both biotype females.
      Global efforts to reduce the level of toxic synthetic insecticides in the
      agricultural environment justify further studies on LBO- and SSO-derived
      materials as potential contact-action fumigants for the control of B. tabaci
      populations.

PMID- 24665713
TI  - Effectiveness of hand removal for small-scale management of Japanese beetles
      (Coleoptera: Scarabaeidae).
AB  - Hand removal is often recommended as a method for small-scale control of Japanese
      beetles (Popillia japonica Newman). In this study, we investigated the
      effectiveness of daily hand removal for controlling damage by Japanese beetles on
      grape plants. We also investigated whether the timing of the removal (at 0800,
      1400, or 1900 hours, or at all 3 periods) influenced the effectiveness of the
      technique. We found that hand removal significantly lowered the number of beetles
      on, and consequently the damage to, grape plants relative to nonremoval controls.
      Of the single removal treatments, removal of beetles at 1900 hours was most
      effective, with results similar to removing beetles three times per day. The
      majority of beetles removed from plants during the experiment were female, a
      pattern that matches our understanding of aggregation formation behavior in the
      species, and which may serve to enhance the benefits of hand removal. Hand
      removal seems to work by decreasing the number of feeding beetles, which in turn
      reduces the release of aggregation kairomones from the plant, and subsequently
      decreases the attractiveness of the plant to future beetles.

PMID- 24665715
TI  - Field distribution of Dasineura oxycoccana (Diptera: Cecidomyiidae) adults,
      larvae, pupae, and parasitoids and evaluation of monitoring trap designs in
      Florida.
AB  - Blueberry gall midge, Dasineura oxycoccana (Johnson), is a pest of cultivated
      blueberries throughout the world. Larvae feed and develop in developing leaf
      buds, and also in flower buds of rabbiteye blueberries, which causes buds to fall
      off the plant. These injuries can cause up to 80% yield loss in heavy
      infestations. As the larvae are protected from insecticides, adults must be
      targeted with foliar applications. Consequently, the detection of adults through
      an effective monitoring program is critical to time insecticide sprays against
      the blueberry gall midge. Understanding the distribution of the midge and its
      parasitoids is also important information for developing a more effective pest
      management program. A comparison of three monitoring trap types demonstrated that
      bucket emergence traps and clear panel traps captured similar numbers of midges,
      although the bucket trap is more sensitive at low population levels. Using bucket
      emergence traps, we found that nearly 80% of the midges collected pupated within
      48 cm of the blueberry bush, suggesting that a targeted soil treatment may be a
      viable integrated pest management tactic that could be included in a midge
      management program. Traps and bud samples demonstrated that adult and larval
      midges and parasitoids were randomly distributed throughout the field in both
      years, with the exception of larval aggregation in early 2012. As parasitoid
      distribution is parallel to host occurrence within blueberry plantings, this
      increases the potential for biological control activities against the blueberry
      gall midge in fields that do not receive broad-spectrum insecticide applications.

PMID- 24665714
TI  - Comparison of food-based attractants for Bactrocera invadens (Diptera:
      Tephritidae) and evaluation of mazoferm-spinosad bait spray for field suppression
      in mango.
AB  - Catches of Bactrocera invadens Drew, Tsuruta, & White (Diptera: Tephritidae) in
      Multi-lure traps baited with six commercial food-based attractants, Mazoferm
      E802, Torula yeast, GF-120, Hymlure, Biolure, and Nulure were compared in mango
      orchards in Kenya. In 2007, Mazoferm E802 and Torula yeast were the most
      effective attractants and captured 2.4-2.6 times more females and 3.4-4.0 times
      more males than the standard Nulure. All attractants captured more females than
      males (ranging from 63 to 74%). In 2008, Mazoferm E802 was the most effective
      bait capturing 5.6 and 9.1 times more females and males, respectively, than the
      standard Nulure. Among all the attractants, in both years, Nulure captured the
      greatest proportion of females: 74% compared with 51-68% for the other
      attractants. In 2008, the use of Mazoferm E802 in combination with spinosad as a
      bait spray in mango orchards reduced B. invadens catches relative to the control
      by 87% within 4 wk and 90% within 8 wk. At harvest, the proportion of fruit
      infested was significantly lower in the treated orchards (8%) compared with the
      control orchards (59%). Estimated mango yield was significantly higher in
      orchards receiving the bait sprays (12,487 kg/ha) compared with control orchards
      (3,606 kg/ha). Based on bait spray costs, yield data, and monetary gains, a cost
      benefit ratio of 1:9.1 was realized, which is acceptable for growers. In 2009,
      the experiment was repeated with similar results. We have demonstrated that
      Mazoferm E802, used alone for monitoring of B. invadens or in conjunction with
      spinosad for population suppression, shows great promise in Kenya.

PMID- 24665716
TI  - Pheromone-assisted techniques to improve the efficacy of insecticide sprays
      against Linepithema humile (Hymenoptera: Formicidae).
AB  - Outdoor residual sprays are among the most common methods for targeting
      pestiferous ants in urban pest management programs. If impervious surfaces such
      as concrete are treated with these insecticides, the active ingredients can be
      washed from the surface by rain or irrigation. As a result, residual sprays with
      fipronil and pyrethroids are found in urban waterways and aquatic sediments.
      Given the amount of insecticides applied to urban settings for ant control and
      their possible impact on urban waterways, the development of alternative
      strategies is critical to decrease the overall amounts of insecticides applied,
      while still achieving effective control of target ant species. Herein we report a
      "pheromone-assisted technique" as an economically viable approach to maximize the
      efficacy of conventional sprays targeting the Argentine ant. By applying
      insecticide sprays supplemented with an attractive pheromone compound, (Z)-9
      hexadecenal, Argentine ants were diverted from nearby trails and nest entrances
      and subsequently exposed to insecticide residues. Laboratory experiments with
      fipronil and bifenthrin sprays indicated that the overall kill of the
      insecticides on Argentine ant colonies was significantly improved (57-142%
      increase) by incorporating (Z)-9-hexadecenal in the insecticide sprays. This
      technique, once it is successfully implemented in practical pest management
      programs, has the potential of providing maximum control efficacy with reduced
      amount of insecticides applied in the environment.

PMID- 24665717
TI  - Field and laboratory efficacy of three insecticides for population management of
      the Asian cockroach (Dictyoptera: Blattellidae).
AB  - Toxicity, repellency, and performance of three insecticides, beta-cyfluthrin EC,
      fipronil granules, and an essential oil EC formulation, were evaluated against
      the Asian cockroach, Blattella asahinai Mizukubo, in field and laboratory
      experiments. The beta-cyfluthrin EC and fipronil granules were significantly more
      toxic than the essential oil EC formulation under continuous exposure conditions,
      with LT50 values of 0.014, 0.45, and 11.45 d, respectively. The beta-cyfluthrin
      EC and fipronil granules were also significantly more toxic than the essential
      oil EC formulation in an Ebeling choice box test with LT50 values of 0.64, 1.98,
      and 59.64 d, respectively. Field applications of insecticides at label rates to
      Asian cockroach populations in Dothan, AL, showed that beta-cyfluthrin EC and
      fipronil granules reduced populations by 100% at 7 and 30 d after treatment. The
      essential oil EC formulation initially reduced populations by 68% at 7 d, but
      control diminished to 2% by 30 d. Results of the field applications and
      laboratory experiments demonstrate that the beta-cyfluthrin EC and fipronil
      granules provide excellent control of Asian cockroach populations.

PMID- 24665718
TI  - Changes in insecticide resistance of the rice striped stem borer (Lepidoptera:
      Crambidae).
AB  - Application of insecticides is the most important method to control Chilo
      suppressalis (Walker) (Lepidoptera: Crambidae), and continuous use of individual
      insecticides has driven the rapid development of insecticide resistance in C.
      suppressalis during the past 30 yr. Monitoring insecticide resistance provides
      information essential for integrated pest management. Insecticide resistance of
      field populations to monosultap, triazophos, chlorpyrifos, and abamectin in China
      was examined in 2010 and 2011. The results indicated that the resistance levels
      of 14 field populations to four insecticides were significantly different. Four
      populations showed moderate resistance, and other populations possessed low-level
      resistance or were susceptible to monosultap. Nine populations displayed an
      extremely high or a high level of resistance to triazophos, whereas four
      populations were sensitive to this agent. Five populations exhibited a low level
      of resistance to abamectin, while the others remained sensitive. When compared
      with historical data, resistance to monosultap and triazophos decreased
      significantly, and the percentage of populations with high-level or extremely
      high-level resistance was obviously reduced. By contrast, the resistance to
      abamectin increased slightly. The increasing and decreasing resistance levels
      reported in this study highlight the different evolutionary patterns of
      insecticide resistance in C. suppressalis. An overreliance on one or two
      insecticides may promote rapid development of resistance. Slow development of
      resistance to abamectin, which was used mainly in mixtures with other
      insecticides, implies that the use of insecticide mixtures may be an effective
      method to delay the evolution of resistance to insecticides.

PMID- 24665719
TI  - Fitness costs associated with field-evolved resistance to Bt maize in Spodoptera
      frugiperda (Lepidoptera: Noctuidae).
AB  - Increasing adoption of transgenic crops expressing cry toxin genes from Bacillus
      thuringiensis (Bt crops) represents an augmented risk for development of insect
      resistance. While fitness costs can greatly influence the rate of resistance
      evolution, most available data related to Bt resistance have been obtained from
      laboratory-selected insect strains. In this article, we test the existence of
      fitness costs associated with high levels of field-evolved resistance to Bt maize
      event TC1507 in a strain of Spodoptera frugiperda (JE Smith) originated from
      maize fields in Puerto Rico. Fitness costs in resistant S. frugiperda were
      evaluated by comparing biological performance to susceptible insects when reared
      on meridic diet, maize or soybean leaf tissue, or cotton reproductive tissues.
      Parameters monitored included larval survival, larval and pupal weights,
      developmental time (larval and pupal), adult longevity, reproductive traits
      (fecundity and fertility), and sex ratio. We found that all monitored parameters
      were influenced to a similar extent by the host, independently of susceptibility
      to Bt maize. The only parameter that significantly differed between strains for
      all hosts was a longer larval developmental period in resistant S. frugiperda,
      which resulted in emergence asynchrony between susceptible and resistant adults.
      To test the relevance of fitness costs in resistant S. frugiperda, we performed a
      selection experiment to monitor the stability of resistance in a heterogeneous
      strain through 12 generations of rearing on meridic diet. Our data demonstrate
      lack of fitness costs relevant to stability of field-evolved resistance to Bt
      maize and help explain reported stability of field-evolved resistance in Puerto
      Rican populations of S. frugiperda.

PMID- 24665720
TI  - Effects of entomopathogens on mortality of western corn rootworm (Coleoptera:
      Chrysomelidae) and fitness costs of resistance to Cry3Bb1 maize.
AB  - Fitness costs can delay pest resistance to crops that produce insecticidal toxins
      derived from the bacterium Bacillus thuringiensis (Bt), and past research has
      found that entomopathogens impose fitness costs of Bt resistance. In addition,
      entomopathogens can be used for integrated pest management by providing
      biological control of pests. The western corn rootworm, Diabrotica virgifera
      virgifera LeConte (Coleoptera: Chrysomelidae), is a major pest of maize and is
      currently managed by planting of Bt maize. We tested whether entomopathogenic
      nematodes and fungi increased mortality of western corn rootworm and whether
      these entomopathogens increased fitness costs of resistance to Cry3Bb1 maize. We
      exposed western corn rootworm larvae to two species of nematodes, Heterorhabditis
      bacteriophora Poinar (Rhabditida: Heterorhabditidae) and Steinernemafeltiae
      Filipjev (Rhabditida: Steinernematidae), and to two species of fungi, Beauveria
      bassiana (Balsamo) Vuillemin (Hypocreales: Cordycipitaceae) (strain GHA) and
      Metarhizium brunneum (Metschnikoff) Sorokin (Hypocreales: Clavicipitaceae)
      (strain F52) in two assay types, namely, seedling mat and small cup. Larval
      mortality increased with the concentration of H. bacteriophora and S. feltiae in
      the small cup assay, and with the exception of S. feltiae and B. bassiana in the
      seedling mat assay, mortality from entomopathogens was significantly greater than
      zero for the remaining entomopathogens in both assays. However, no fitness costs
      were observed in either assay type for any entomopathogen. Increased mortality of
      western corn rootworm larvae caused by these entomopathogens supports their
      potential use in biological control; however, the lack of fitness costs suggests
      that entomopathogens will not delay the evolution of Bt resistance in western
      corn rootworm.

PMID- 24665721
TI  - A method to estimate the population level of Aceria litchii (Prostigmata:
      Eriophyidae) and a study of the population dynamics of this species and its
      predators on litchi trees in southern Brazil.
AB  - Litchi (Litchi chinensis Sonnerat) is native to Southeast Asia, where most of the
      world cultivation of this crop is done. Its commercial cultivation in Brazil is
      recent and concentrated in the state of Sao Paulo. This crop has been severely
      damaged in Asia and Brazil by the litchi erineum mite, Aceria litchii (Keifer)
      (Eriophyidae). The objectives of this study were the adaptation of a method to
      estimate the density of A. litchii, an evaluation of the population dynamics of
      this pest and of its associated predators in the state of Sao Paulo, and an
      estimation of its injury levels to litchi trees. To estimate the density of A.
      litchii, an adaptation of a method commonly used to evaluate nematode densities
      in plant roots was performed. This method was shown to be adequate for the
      estimation of the number of A. litchii, and it might also be useful for similar
      evaluations of other erineum forming mites. Field samples to determine the pest
      population dynamics were collected monthly from August 2011 to July 2012. Sampled
      leaves were examined under a stereomicroscope for removal of predators and
      subsequent extraction ofA. litchii by the adapted method. A. litchii reached
      maximum densities in November 2011 and June 2012, being found at low densities
      between January and March 2012. The pattern of variation of A. litchii injury
      levels was similar to that of the density of A. litchii. The main predatory mite
      co-occurring with A. litchii was the phytoseiid Phytoseius intermedius Evans and
      McFarlane. However, high injury levels due toA. litchii suggest that the predator
      was unable to prevent visible damages to the trees, indicating that control
      activities should be adopted by growers.

PMID- 24665722
TI  - Susceptibility and aversion of Spodoptera frugiperda (Lepidoptera: Noctuidae) to
      Cry1F Bt maize and considerations for insect resistance management.
AB  - Bacillus thuringiensis (Bt) maize was developed primarily for North American
      pests such as European corn borer (Ostrinia nubilalis (Hubner)). However, most Bt
      maize products are also cultivated outside of North America, where the primary
      pests may be different and may have lower susceptibility to Bt toxins. Fall
      armyworm (Spodoptera frugiperda JE Smith) is an important pest and primary target
      of Bt maize in Central and South America. S. frugiperda susceptibility to Cry1F
      (expressed in event TC1507) is an example of a pest-by-toxin interaction that
      does not meet the high-dose definition. In this study, the behavioral and toxic
      response of S. frugiperda to Cry1F maize was investigated by measuring the
      percentage of time naive third instars spent feeding during a 3-min exposure. S.
      frugiperda also were exposed as third instars to Cry1F maize for 14 d to measure
      weight gain and survival. S. frugiperda demonstrated an initial, postingestive
      aversive response to Cry1F maize, and few larvae survived the 14 d exposure. The
      role of susceptibility and avoidance are discussed in the context of global IRM
      refuge strategy development for Bt products.

PMID- 24665723
TI  - Susceptibility of 15 mango (Sapindales: Anacardiaceae) cultivars to the attack by
      Anastrepha ludens and Anastrepha obliqua (Diptera: Tephritidae) and the role of
      underdeveloped fruit as pest reservoirs: management implications.
AB  - We evaluated the susceptibility of 15 mango cultivars to the attack of Anastrepha
      ludens (Loew) and Anastrepha obliqua (Macquart) (Diptera: Tephritidae), the main
      tephritid pests of this crop in Mexico. In a field experiment, bagged fruit
      bearing branches were exposed to gravid females of both fly species. Infestation
      rates, developmental time, adult eclosion, and F1 adult longevity, fecundity, and
      fertility were recorded, ranking cultivars in terms of susceptibility to fly
      attack and development. We also compared the volatile profile in selected
      resistant and susceptible cultivars in search of possible correlations. In a
      second experiment, clutch size for A. ludens was determined in each cultivar.
      Infestation rates, developmental time, and F1 demographic parameters varied
      sharply among cultivars and between fly species for bagged fruit. Cultivars
      'Vishi,' '74-82,' and 'Brooks' were most susceptible to A. ludens infestation
      while "Tommy,' 'Sensation,' and 'Ataulfo "nino"' (parthenocarpic fruit) were most
      susceptible to A. obliqua infestation. 'Edward,' 'Kent,' 'Brooks late,' 'Palmer,
      and 'Ataulfo' exhibited tolerance to attack of both fly species. Fruit of
      susceptible and resistant cultivars exhibited unique volatile profiles. Fly
      development and F1 adult demographic parameters varied significantly among
      cultivars. A. ludens females laid larger clutches in larger and harder fruit. We
      highlight the important role of Ataulfo "nino" as pest reservoir if fruit is left
      unharvested on trees. We discuss the possible use of highly resistant cultivars
      as trap crops or egg sinks.

PMID- 24665724
TI  - Transient heat stress compromises the resistance of wheat (Poales: Poaceae)
      seedlings to Hessian fly (Diptera: Cecidomyiidae) infestation.
AB  - Heat stress exerts a profound impact on the resistance of plants to parasites. In
      this research, we investigated the impact of an acute transient heat stress on
      the resistance of the wheat line 'Molly,' which contains the R gene H13, to an
      avirulent Hessian fly (Mayetiola destructor (Say)) population. We found that a
      significant portion of Molly seedlings stressed at 40 degrees C for 6 h during or
      after the initial Hessian fly larval attack became susceptible to otherwise
      avirulent insects, whereas unstressed control plants remained 100% resistant.
      Specifically, 77.8, 73.3, 83.3, and 46.7% of plants heat stressed at 0, 6,12, and
      24 h, respectively, after the initial larval attack became susceptible.
      Biochemical analysis revealed that heat stress caused a transient decrease in 12
      oxo-phytodienoic acid, but an increase in salicylic acid accumulation in Molly
      plants. The change in phytohormones after heat stress and Hessian fly infestation
      was not observed in 'Newton,' a near-isogenic but Hessian fly susceptible wheat
      line. Instead, heat stress caused a relatively prolonged reduction in palmitoleic
      acid. The role of phytohormones in heat-induced loss of wheat resistance was
      discussed.

PMID- 24665725
TI  - How many adults of Mahanarva spectabilis (Hemiptera: Cercopidae) should be used
      for screening Brachiaria ruziziensis (Poales: Poaceae) resistance?
AB  - This study determined the number of spittlebug adults, Mahanarva spectabilis
      Distant (Hemiptera: Cercopidae), that should be used in selection tests of the
      forage grass, Brachiaria ruziziensis (Germain and Evrard). In this study, 0, 1,
      2, 4, or 8 M. spectabilis adults were kept in plants for 4 or 8 d per
      experimental plot. After these periods, the insects were removed from the plants
      and chlorophyll content, damage score, dry weight, fresh weight, and percent dry
      matter of shoots were evaluated. Chlorophyll content decreased significantly with
      higher density of M. spectabilis in plants exposed to the pest for 4 or 8 d.
      Plants that were exposed to eight spittlebugs for 8 d showed a approximately 60%
      loss of chlorophyll content. When the forage was infested with eight adults for 4
      d, the average damage score was 3 (50% of the leaf area was affected). The damage
      score and fresh and dry weights of the forage did not change depending on the
      exposure time of the plants to the spittlebugs. The percentage of dry matter of
      the plants infested was higher with the increase insect density and exposure time
      for all densities. Thus, the minimum recommended number is eight M. spectabilis
      adults for 4 d in resistance tests of B. ruziziensis to this pest species.

PMID- 24665726
TI  - Efficacy of pyramided Bt proteins Cry1F, Cry1A.105, and cry2Ab2 expressed in
      Smartstax corn hybrids against lepidopteran insect pests in the northern United
      States.
AB  - Commercial field corn (Zea mays L.) hybrids transformed to express some or all of
      the lepidopteran insect-resistant traits present in SmartStax corn hybrids were
      evaluated for insecticidal efficacy against a wide range oflepidopteran corn
      pests common to the northern United States, during 2008 to 2011 at locations in
      15 states. SmartStax hybrids contain a pyramid of two Bacillus thuringiensis (Bt)
      derived events for lepidopteran control: event TC1507 expressing Cry1F protein
      and MON 89034 expressing CrylA.105 + Cry2Ab2. These studies focused on
      characterization of the relative efficacy of each event when expressed alone or
      in combination, and compared with non-Bt hybrid. Corn hybrids containing
      pyramided insecticidal proteins Cry1F + Cry1A.105 + Cry2Ab2 (SmartStax)
      consistently showed reduced plant feeding damage by a wide range of lepidopteran
      larvae compared with single event and non-Bt hybrids. Corn hybrids expressing
      TC1507 or MON 89034 as single or pyramided events were consistently efficacious
      against Ostrinia nubilalis (Hubner). SmartStax hybrids had less injury from
      Agrotis ipsilon (Hufnagel) and Striacosta albicosta (Smith) than corn hybrids
      containing only event MON 89034 but were not more efficacious than single event
      TC1507 hybrids. Corn hybrids with event MON 89034 provided better control of
      Helicoverpa zea (Boddie), than event TC1507 alone. Spodoptera frugiperda (J.E.
      Smith) efficacy was higher for hybrids with pyramid events and single events
      compared with the non-Bt hybrids. The spectra of activity of events TC1507 and
      MON 89034 differed. The combination of TC1507 + MON 89034 provided redundant
      control of some pests where the spectra overlapped and thereby are expected to
      confer a resistance management benefit.

PMID- 24665727
TI  - Antixenosis resistance to Oulema melanopus (Coleoptera: Chrysomelidae) in central
      Asian wheat germplasm.
AB  - ABSTRACT The cereal leaf beetle, Oulema melanopus (L.) (Coleoptera:
      Chrysomelidae), which is Eurasian in origin, is an emerging pest of
      agriculturally important cereal crops in western Canada, including wheat, oat,
      and barley. Among these crops, wheat (Triticum aestivum L.) has the highest
      number of resistant genotypes to O. melanopus infestation. Here we explored six
      genotypes from central Asia with putative resistance to the beetle in comparison
      with a widely grown Canadian wheat variety. We noted the highest oviposition on
      the susceptible control genotype, CDC GO, and the lowest on one of the central
      Asian genotypes (NN-100) in both choice and no-choice tests. Two of the other
      Asian genotypes (NN-78 and NN-105) were also less attractive for oviposition than
      the CDC GO check. Feeding trials also indicated less damage on some of the Asian
      genotypes (NN-100, NN-105, and NN-78) relative to CDC GO, but other Asian
      genotypes (NN-41, NN-45, and NN-27) were highly attractive for feeding and
      oviposition and did not exhibit stronger resistance to O. melanopus infestation
      than moderately resistant central Asian genotypes (NN-103, NN-78, or NN-105).
      There were no significant differences in the amount of feeding by overwintered
      and teneral adults. The results indicated that some wheat genotypes developed in
      central Asia have categories of nonpreference for feeding and oviposition worth
      considering in further development of host-plant resistance and integrated
      management of this pest.

PMID- 24665728
TI  - Virulence and biotype analyses of Hessian fly (Diptera: Cecidomyiidae)
      populations from Texas, Louisiana, and Oklahoma.
AB  - Hessian fly, Mayetiola destructor (Say, 1817), is a major pest of wheat, and is
      controlled mainly through deploying fly-resistant wheat cultivars. The challenge
      for the plant resistance approach is that virulence of Hessian fly populations in
      the field is dynamic, and wheat cultivars may lose resistance within 6-8 yr. To
      ensure continuous success of host plant resistance, Hessian fly populations in
      the field need to be constantly monitored to determine which resistance genes
      remain effective in different geographic regions. This study investigated five
      Hessian fly populations collected from Texas, Louisiana, and Oklahoma, where
      infestation by Hessian fly has been high in recent years. Eight resistance genes,
      H12, H13, H17, H18, H22, H25, H26, and Hdic, were found to be highly effective
      against all tested Hessian fly populations in this region, conferring resistance
      to > or = 80% of plants containing one of these resistance genes. The frequencies
      ofbiotypes virulent to resistance genes H13 (biotype vH13), H18 (vH18), H21
      (vH21), H25 (vH25), H26 (vH26), and Hdic (vHdic) were determined, and were found
      to vary from population to population, ranging from 0 to 45%. A logistic
      regression model was established to predict biotype frequencies based on the
      correlation between the percentages of susceptible plants obtained in a virulence
      test and the log-odds of virulent biotype frequencies determined by a traditional
      approach.

PMID- 24665729
TI  - Evaluation of tetraploid switchgrass (Poales: Poaceae) populations for host
      suitability and differential resistance to four cereal aphids.
AB  - Switchgrass, Panicum virgatum L., is being developed as a bioenergy feedstock.
      The potential for large-scale production has encouraged its evaluation as a host
      for important grass pests. Eight no-choice studies were performed for two
      developmental stages of two switchgrass cultivars ('Kanlow' and'Summer') and two
      experimental strains, K x S, and S x K produced by reciprocal mating of these
      cultivars followed by selection for high yield. Plants were evaluated for host
      suitability and damage differences to herbivory by four important cereal aphids,
      Sipha flava (Forbes), Schizaphis graminum (Rondani) (biotype I), Rhopalosiphum
      padi (L.), and Diuraphis noxia (Mordvilko). All switchgrasses were found to be
      unsuitable feeding and reproductive hosts to R. padi and D. noxia, which were
      unable to establish on the plants. However, both S. flava and S. graminum were
      able to establish on all switchgrasses tested. Differential levels of resistance
      to S. flava and S. graminum were detected among the switchgrasses by both
      cumulative aphid days (CAD) and plant damage ratings. Kanlow was consistently
      rated as highly resistant based on CAD and damage ratings for both aphid species,
      while Summer was consistently among the most susceptible to both aphids at both
      developmental stages, with relatively high damage ratings. The resistance of the
      K x S and S x K populations in relationship to their Summer and Kanlow parents
      indicted that they inherited some resistance to S. graminum and S. flava from
      their Kanlow parent. These studies provide valuable baseline information
      concerning the host suitability of switchgrass to four cereal aphids and the
      plant-insect interactions within a system that has been largely overlooked and
      indicate that there are genetic differences among switchgrass populations for
      resistance to some insects.

PMID- 24665730
TI  - Inference on arthropod demographic parameters: computational advances using R.
AB  - We developed a computer program for life table analysis using the open source,
      free software programming environment R. It is useful to quantify chronic
      nonlethal effects of treatments on arthropod populations by summarizing
      information on their survival and fertility in key population parameters referred
      to as fertility life table parameters. Statistical inference on fertility life
      table parameters is not trivial because it requires the use of computationally
      intensive methods for variance estimation. Our codes present some advantages with
      respect to a previous program developed in Statistical Analysis System.
      Additional multiple comparison tests were incorporated for the analysis of
      qualitative factors; a module for regression analysis was implemented, thus,
      allowing analysis of quantitative factors such as temperature or agrochemical
      doses; availability is granted for users, once it was developed using an open
      source, free software programming environment. To illustrate the descriptive and
      inferential analysis implemented in lifetable.R, we present and discuss two
      examples: 1) a study quantifying the influence of the proteinase inhibitor
      berenil on the eucalyptus defoliator Thyrinteina arnobia (Stoll) and 2) a study
      investigating the influence of temperature on demographic parameters of a
      predaceous ladybird, Hippodamia variegata (Goeze).

PMID- 24665731
TI  - Spatial pattern in aerosol insecticide deposition inside a flour mill.
AB  - Aerosol insecticides are commonly used for management of stored-product pests
      inside food facilities, but the physical complexity of the interior of most food
      facilities may influence the dispersal and deposition of droplets and create
      spatial variation in dosage. The spatial pattern in aerosol deposition was
      evaluated inside a flour mill using a high density grid of bioassay insects.
      Three insecticides, Aerotech with NyGuard and Pyrocide 100 + Diacon II, both
      pyrethrin and insect growth regulator combinations, and Vap20, an
      organophosphate, were evaluated at normal (27 degrees C) and high (40 degrees C)
      target temperatures. Using a newly developed efficacy index, there was spatial
      pattern to aerosol deposition detected for the pyrethrin insecticides and the
      pattern differed between aerosols and temperatures. Walls and corners, especially
      behind the direction of application, were especially vulnerable to zones of lower
      efficacy, and open areas in center of the room tended to have the highest
      efficacy. The organophosphate insecticide provided complete efficacy at all
      bioassay dish locations, probably due in part to its vapor toxicity. Using boxes
      1 m in depth and 5, 10, or 20 cm in height and open on only one end, it was shown
      that aerosol dispersal under horizontal surfaces could be impacted by gap height,
      aerosol, and temperature. These results show the potential for spatial variation
      in aerosol efficacy within a food facility and identify locations with the
      potential to receive a lower insecticide dosage. To increase overall efficacy,
      these locations may be targeted for additional interventions to provide more
      uniform pest population suppression.

PMID- 24665732
TI  - An inexpensive feeding bioassay technique for stored-product insects.
AB  - ABSTRACT We used the red flour beetle, Tribolium castaneum Herbst (Coleoptera:
      Tenebrionidae), to compare three feeding bioassay techniques using flour disks.
      The area (scanner or digital photographs) and mass (sensitive balance) of the
      same flour disks were measured daily for 1 or 2 wk to assess feeding by insects.
      The loss in mass and area over 4 h was measured, as some variation over time was
      noticed in the disks with no insects feeding on them. The gravimetric method
      correlated well with both measurements of the area for the disks held in a growth
      chamber: scanner (R2 = 0.96), digital photography (R2 = 0.96). There was also a
      high correlation (R2 = 0.86) between the disk weight and area scanned at normal
      lab conditions. There were differences in the percentage of the disks remaining
      over time depending on the temperature and whether they were weighed or scanned.
      Measuring the mass of the disks resulted in a relatively larger percent of disk
      remaining compared with the scanned area. Mass measurements required a sensitive
      balance, handling of the disks and the insects, and appeared slightly more
      sensitive to humidity and temperature changes over time. Scanning the disks
      requires flat bed scanner access but less handling of both insects and disks.
      Digital photographs could be taken quickly, requiring less equipment, although
      photographs had to be further processed to determine area Scanning or taking
      digital photographs of flour disk area was an effective technique for measuring
      insect feeding.

PMID- 24665733
TI  - Evaluation of synergized pyrethrin aerosol for control of Tribolium castaneum and
      Tribolium confusum (Coleoptera: Tenebrionidae).
AB  - Aerosol insecticides are being used in flour mill pest management programs, but
      there is limited information on their efficacy on different insect life stages.
      In this study, we evaluated the efficacy of synergized pyrethrin applied as an
      aerosol against eggs, larvae, pupae, and adults of the red flour beetle,
      Tribolium castaneum (Herbst), and the confused flour beetle, Tribolium confusum
      Jacquelin du Val. Effects of direct and indirect exposure were evaluated by
      exposing each life stage to the aerosol and then transferring to untreated flour,
      transferring untreated insects to treated flour, or exposing both the insects and
      the flour to the aerosol. The aerosol produced >88% mortality of both species and
      all life stages when insects were directly treated and transferred to either
      treated or untreated flour. Mortality was significantly reduced when insects were
      either treated together with flour or untreated insects were transferred to
      treated flour (indirect exposure to the aerosol). Larvae and adults of both
      species were more tolerant compared with eggs and pupae. Recovery of moribund
      adults in the indirect exposure treatments was greater compared with recovery of
      moribund insects in the direct exposure treatments. Good sanitation before
      aerosol application could facilitate direct exposure of insects and thus increase
      aerosol efficacy inside flour mills.

PMID- 24665734
TI  - Effect of abiotic factors on initiation of red flour beetle (Coleoptera:
      Tenebrionidae) flight.
AB  - Traps baited with pheromones are used to monitor the red flour beetle, Tribolium
      castaneum (Herbst) (Coleoptera-Tenebrionidae), populations in flour mills to aid
      in making pest management decisions, but the factors that influence T. castaneum
      movement are not fully understood. We investigated the impact of photoperiod,
      light intensity, temperature, and relative humidity on flight initiation. The
      percentage of adults initiating flight reached a maximum at 30 -35 degrees C, and
      then fell to zero at 22.5 and 45 degrees C. Only 2% of beetles flew in complete
      darkness, and the number of beetles initiating flight increased to 41% under 18 h
      of light and then decreased slightly to 37% under 24 h of light. Rates of flight
      initiation did not vary with light intensities from 1,784 to 4,356 lux or
      relative humidities from 25 to 85%. Thus, temperature and photoperiod are the
      main abiotic factors tested that impact flight initiation in T castaneum, which
      have broad ranges of temperatures and photoperiods over which they can fly. The
      current results should be useful in helping to interpret trap catches based on
      abiotic conditions during the trapping period, and the results should be useful
      in helping to understand T. castaneum movement outside grain storages and
      processing facilities and their potential to infest structures.

PMID- 24665735
TI  - Attract-and-Kill and other pheromone-based methods to suppress populations of the
      Indianmeal moth (Lepidoptera: Pyralidae).
AB  - Three attract-and-kill formulations, a gel, a wax panel, and a plastic cylinder
      were tested in simulated warehouses at three densities of devices and at three
      densities of moths, Plodia interpunctella Hubner, per room. Wax panels and the
      cylinder formulations suppressed all the densities of moths with only one device
      per room. Two field experiments were then conducted during 2005 and 2006 in
      replicated commercial pet food and grocery stores that harbored natural
      populations of P. interpunctella. In the summer of 2005, the wax panel
      formulation suppressed adult male response to monitoring traps and also reduced
      the numbers of larvae in food bait oviposition cups after the first month of
      being established. This suppression was maintained until the third month. The
      second field experiment in 2006 compared three pheromone-based methods of moth
      suppression in buildings with moth populations in untreated buildings. The mass
      trapping treatment showed the lowest adult moth capture after the first month of
      the experiment until the end of the third month. However, this treatment was
      similar statistically to use of attract-and-kill panels, mating disruption, and
      untreated control establishments in most of the weeks. Monitoring of larvae in
      food cups revealed the pheromone-based methods were not significantly different
      from each other, but that they suppressed moth populations in most of the weeks
      when compared with untreated control buildings. This research shows potential for
      successful pheromone-based suppression methods for Indianmeal moths in commercial
      applications.

PMID- 24665736
TI  - [Reflection on the "publication bazaar"--academic evaluation and research
      integrity in China].

PMID- 24665737
TI  - [Regulation on EGFR function via its interacting proteins and its potential
      application].
AB  - Epidermal growth factor receptor (EGFR) is imptortant for cell activities,
      oncogenesis and cell migration, and EGFR inhibitor can treat cancer efficiently,
      but its side effects, for example, in skin, limited its usage. On the other hand,
      EGFR interacting proteins may also lead to oncogenesis and its interacting
      protein as drug targets can avoid cutaneous side effect, which implies possibly a
      better outcome and life quality of cancer patients. For the multiple EGFR
      interaction proteins, B1R enhances Erk/MAPK signaling, while PTPN12, Kek1,
      CEACAM1 and NHERF repress Erk/MAPK signaling. CaM may alter charge of EGFR
      juxamembrane domain and regulate activation of PI3K/Akt and PLC-gamma/PKC. STAT1,
      STAT5b are widely thought to be activated by EGFR, while there is unexpectedly
      inhibiting sequence within EGFR to repress the activity of STATs. LRIG1 and ACK1
      enhance the internalization and degration of EGFR, while NHERF and HIP1 repress
      it. In this article, proteins interacting with EGFR, their interacting sites and
      their regulation on EGFR signal transduction will be reviewed.

PMID- 24665738
TI  - [Current understanding of sleep, dreaming and related memory consolidation].
AB  - Sleep is a naturally recurring state found throughout the animal kingdom and
      characterized by a reversible loss of consciousness. Although in humans the daily
      amount of sleep decreases with aging, the total amount of time spent for sleep is
      estimated as up to one-third of one's lifetime. In mammals, sleep shows a clear
      daily rhythmicity as well as nightly phases, which are strongly controlled by the
      circadian clock located in the hypothalamic suprachiasmatic nuclei and are also
      regulated by ambient light. While it is certain that sleep is critical for
      survival in general, the functional significance of sleep is still under
      investigation. Dreaming is a common psychological phenomenon occurring during
      human sleep, yet its content and natural function, if any, are still a matter of
      debate. In recent years, accumulated evidence strongly supports the notion that
      new information acquired during the day time is processed and transformed into
      long-term memory in a complicated and sophisticated way during sleeping. Such
      information processing is commonly referred to as memory consolidation.

PMID- 24665739
TI  - [Progress in research of the mechanisms related with the hepatic steatosis in the
      nonalcoholic fatty liver disease].
AB  - With the increased morbidity of Nonalcoholic fatty liver disease, the
      pathogenesis of which has become one of the focuses for researchers. Many details
      need to be clarified. The hepatic steatosis has been taken as the clinical
      pathological characters and the "golden standard of diagnosis" for the
      nonalcoholic fatty liver disease. More and more studies have shown that the
      hepatic steatosis (mainly as triglycerides) is the consequence of hepatic lipid
      metabolism disequilibrium. Generally, the related metabolism pathways including
      lipid input, lipid uptake, de novo lipogenesis, fatty acid oxidation, fatty acid
      reesterification, and lipid secretion etc. In this review, we focused on the
      progress of some key enzymes involved in these pathways in order to clarify the
      possible molecular mechanisms and the effective targets so that to broad our
      vision about the prevention and treatment of non-alcoholic fatty liver disease.

PMID- 24665740
TI  - [FXR and its influence on hepatobiliary and gastrointestinal diseases].
AB  - Farnesoid X receptor (FXR), a bile acid receptor, serves as a member of the
      nuclear receptor superfamily. It plays a pivotal role in regulating hepatic
      inflammation and regeneration. Recent evidence suggests, that FXR and the bile
      acid are involved in diseases such as cholestatic and inflammatory liver
      diseases, hepatocellular carcinoma, and bacterial translocation. In this review
      we discuss the pathophysiology influence of FXR and the bile acid on liver,
      biliary and gastrointestinal diseases and its mechanisms.

PMID- 24665741
TI  - [PANDER in regulation of glucose and lipid metabolism].

PMID- 24665742
TI  - [Cardiovascular effects and pathophysiological significance of vasostatins].

PMID- 24665743
TI  - [Mechanisms mediating renal sympathetic activation in obesity-related
      hypertension].

PMID- 24665744
TI  - [Research progress of fast action of estrogen mediated by GPR30/GPER].

PMID- 24665745
TI  - [The research progress of post-translational modification of androgen receptor].

PMID- 24665746
TI  - [calpain 10 and glucose metabolism].

PMID- 24665747
TI  - [Biological researches of the relationship between TPH2 gene and stress
      response].

PMID- 24665748
TI  - [FOXP2 and its relevance to language].

PMID- 24665749
TI  - [Regulation of GDNF on drug addiction and its mechanism].

PMID- 24665750
TI  - [The role of RNA editing in serotonin 2C receptor].

PMID- 24665751
TI  - [The relevance between the import roles for alpha-synuclein in neurotransmitter
      release and the progress of Parkinsons disease].

PMID- 24665752
TI  - [The roles of FGF-2, inflammatory factor, nuclear factor-kappaB that cause
      endothelial mesenchymal transition in cornea].

PMID- 24665753
TI  - [Tradition and innovation in scientific research].

PMID- 24665754
TI  - Cambial periodicity and wood production in Acacia ehrenbergiana Hayne growing on
      dry sites of Saudi Arabia.
AB  - This study aimed at elucidating the process of cambial activity and wood
      formation in Acacia ehrenbergiana Hayne growing in the Al-Baha region of Saudi
      Arabia, has revealed that the vascular cambium was active for almost the whole
      year, producing phloem in two flushes (February-March and August-October), and
      xylem for about 11 months, with varying pace of cell division and
      differentiation. A close relationship existed between emergence of new leaves and
      initiation/acceleration of cambial activity and tissue differentiation. Monthly
      average of the maximum and mean daily temperature showed negative correlation
      with cambial-zone width. Relative humidity showed positive relationship with
      xylem differentiation. Leaf water deficit had an adverse effect on the cambial
      activity (r = -0.94, p < 0.01), xylem production (r = -0.93, p < 0.01) and phloem
      production (r = -0.97, p < 0.01). On the whole, moderate temperature, low water
      deficit and high relative humidity and rainfall favored cambial activity and
      vascular tissue formation. Annual production of xylem was about five times that
      of phloem. A. ehrenbergiana appears to be a drought-tolerant species by having
      narrow, dense and thick-walled vessels, thick-walled fibers, high wood density
      (0.9273 g cm(-3)), low vulnerability factor (4.20) and the capacity of thriving
      well at 35 to 47% water-saturation deficit.

PMID- 24665755
TI  - Effect of nitrogen fertigation and sowing time on the expression of Cry2Ab and on
      mortality of Spodoptera litura in Bollgard II cotton.
AB  - Toxin expression of Cry2Ab was studied in plant parts of Bollgard II cotton
      genotype MRC 7031 sown under different treatments of nitrogen application and
      planting dates. The expression was quantified by using Cry2Aa ELISA kit. Mean per
      cent mortality of one-day-old, 3rd and 5th instar larvae of Spodoptera litura was
      observed on different plant parts of MRC 7031 and their respective non-Bt cotton
      genotypes. The study deduced that mean maximum expression (19.24, 20.93 and 20.71
      microg g(-1) in leaves, squares and bolls, respectively) of Cry2Ab was observed
      at higher nitrogen dose @ 300 kg ha(-1) (N3), while it was minimum (18.67, 20.44
      and 20.14 microg g(-1) in leaves, squares and bolls, respectively) at low
      nitrogen dose @ 150 kg ha(-1) (N1). Studies conducted for different planting
      dates showed mean maximum expression (18.98, 20.72 and 20.42 microg g(-1) in
      leaves, squares and bolls, respectively) of Cry2Ab during late sown crop (15th
      May) as compared to early sown crop (15th April), the expression was 18.66, 20.32
      and 20.06 microg g(-1) in leaves, squares and bolls, respectively. Quantitative
      expression of Cry2Ab was found to vary among different plant parts, i.e more in
      squares followed by bolls and leaves. Regarding mortality of different instars of
      S. litura, it was significantly more at higher nitrogen doses and it ranged from
      83.04 to 96.27, 53.38 to 61.87 and 16.87 to 22.58% in case of S. litura one-day
      old larvae, 3rd and 5th instar, respectively. While, non significant difference
      in mortalitywas observed during different sowing dates.

PMID- 24665756
TI  - Effect of salt stress on morpho-physiology, vegetative growth and yield of rice.
AB  - Selection of salt tolerant rice varieties has a huge impact on global food supply
      chain. Five Malaysian rice (Oryza sativa L.) varieties, MR33, MR52, MR211, MR219
      and MR232 were tested in pot experiment under different salinity levels for their
      response in term of vegetative growth, physiological activities, development of
      yield components and grain yield. Rice varieties, BRRI dhan29 and IR20 were used
      as a salt-sensitive control and Pokkali was used as a salt-tolerant control.
      Three different salinity levels viz. 4, 8, and 12 dS m(-1) were used in a
      randomized complete block design with four replications under glass house
      conditions. Two Malaysia varieties, MR211 and MR232 performed better in terms of
      vegetative growth (plant height, leaf area plant(-1), number of tillers plant(
      1), dry matter accumulation plant(-1)), photosynthetic rate, transpiration rate,
      yield components, grain yield and injury symptoms. While, MR33, MR52 and MR219
      verities were able to withstand salinity stress over salt-sensitive control, BRRI
      dhan29 and IR20.

PMID- 24665757
TI  - Larvicidal potential of wild mustard (Cleome viscosa) and gokhru (Tribulus
      terrestris) against mosquito vectors in the semi-arid region of Western
      Rajasthan.
AB  - Cleome viscosa L. (Family: Capparaceae) commonly known as Tickweed or wild
      mustard and Tribulus terrestris L. (Family: Zygophyllaceae) commonly known as
      Gokhru, growing wildly in the desert areas in the monsoon and post monsoon
      season, are of great medicinal importance. Comparative larvicidal efficacy of the
      extracts from seeds of C. viscosa and fruits and leaves of T. terrestris was
      evaluated against 3rd or early 4th stage larvae of Anopheles stephensi (Liston),
      Aedes aegypti (Linnaeus) and Culex quinquefasciatus (Say) in different organic
      solvents. 24 and 48 hr LC50 and LC90 values along with their 95% fiducial limits,
      regression equation, chi-square (chi2)/ heterogeneity of the response was
      determined by log probit regression analysis. The 24 hr LC50 values as determined
      for seeds of C. viscosa were 144.1, 99.5 and 127.1 (methanol); 106.3, 138.9 and
      118.5 (acetone) and 166.4, 162.5 and 301.9 mg l(-1) (petroleum ether extracts)
      for all the three mosquito species respectively showing that methanol and acetone
      extracts were a little bit more effective than the petroleum ether extracts.
      Experiments were carried out with fruits and leaves of T. terrestris with all the
      solvents and mosquito species. The 24 hr LC50 values, as determined for fruits of
      T. terrestris were 70.8, 103.4 and 268.2 (methanol); 74.0,120.5 and 132.0
      (acetone) and 73.8,113.5 and 137.4 mg l(-1) (petroleum ether extracts) while the
      24 hr LC50 values for leaves were 124.3, 196.8 and 246.5 (methanol); 163.4, 196.9
      and 224.3 (acetone) and 135.8, 176.8 and 185.9 mg l(-1) (petroleum ether
      extracts) for all the three mosquito species respectively. The results clearly
      indicate that fruit extracts of T. terrestris were more effective as compared to
      leaves extracts in the three solvents tested. Larvae of An. stephensi were found
      more sensitive to both fruit and leaves extracts of T. terrestris followed by
      larvae of Ae. aegypti and Cx. quinquefasciatus. Extracts from the seeds of C.
      viscosa were found less effective as compared to the fruit extracts of T.
      terrestris indicating that active larvicidal principle may be present in the
      fruits of this plant species. The studywould be of great importance while
      formulating the control strategy, for vectors of malaria, dengue and lymphatic
      filariasis, based on alternative plant based insecticides in this semi-arid
      region.

PMID- 24665758
TI  - Study on individual and interactive effects of supplemental UV-B radiation and
      heavy metals on Spinacea oleracea.
AB  - The effects of supplemental ultraviolet-B (sUV-B) irradiation and heavy metals
      (Cd and Ni) treatment alone and in combination were evaluated on the growth,
      biomass and yield of spinach plants. All the stresses caused reduction in biomass
      yield vis-a-vis alteration in its distribution pattern with more retention in
      below ground parts leading to higher root shoot ratio. Absolute growth rate (AGR)
      decreased in all treated plants due to reduction in their height at successive
      growth stages. Decrease in leaf area and number of leaves due to various stresses
      was responsible for decline in net assimilation rate (NAR), an index of
      photosynthetic assimilatory capacity of the plant. Supplemental UV-B increased
      the bioaccumulation of Cd and Ni in the root and shoot of exposed plants as
      compared to the control ones. The present study suggested that soil contaminated
      with Cd or Ni had a more negative impact on yield with higher retention of heavy
      metals in spinach growing under natural field conditions and exposed with
      elevated UV-B.

PMID- 24665759
TI  - Seasonal variation of antibacterial activities in the green alga Ulva pertusa
      Kjellman.
AB  - The present study was performed to screen out the extracts of algae and assess
      the seasonal variation in antimicrobial activity of Ulva pertusa against
      Gardnerella vaginalis. Seasonal variation in antibacterial activity was observed,
      with the extracts showing no activity during summer and autumn, and showing
      antibacterial activity from early winter (December) to middle spring (April). The
      maximum value of antimicrobial activity (6.5 mm inhibition zone at 5 mg disk(-1))
      of U. pertusa against G. vaginalis was observed in April. Otherwise, for both
      chlorophyll a and b, the highest content (2.87 mg g(-1) and 1.37 mg g(-1)) was
      observed in March 2009. These results may reflect variation in cellular chemical
      compositions such as secondary metabolite(s) rather than chlorophyll and
      biological activities according to season.

PMID- 24665760
TI  - Reproductive biology of Indian Silurid catfish Ompok pabda in river Gomti.
AB  - Reproductive biology of an Indian Silurid catfish, Ompok pabda were determined in
      a moderately impacted tropical River Gomti in India. Samples offish were
      collected monthly between May 2008 to April 2009 in two zones; upstream site at
      Mishrikh, Sitapur and midstream site at Lucknow. Length at first maturity
      calculated through maturity curve was 12.9 cm (males) and 13.9 cm (females) in
      total length. The gonado-somatic index indicated that spawning generally occurred
      between June - September and sex ratio showed a predominance of females,
      representing 54.3% of the total sample. The fecundity was found to vary from 2460
      to 5986 nos, with mean of 4330 +/- 799 for the fish with total length of 11.5
      20.0 cm. The relationship of fecundity with total length and total body weight of
      the fish was Log F = 0.374 Log L+ 0.37, r2 = 0.999 and Log F = 0.337 Log W-0.40,
      r2 = 0.966. The well defined traits of O. pabda from the Ganges basin provide
      basic information which can be further used for species conservation planning.

PMID- 24665761
TI  - Effect of bacterial growth period on the sensitivity of the MTT assay for silver.
AB  - Respiratory activity inhibition by toxic compounds in bacteria and yeast has been
      used to detect toxic compounds in the environment. Often the age of culture
      contributes towards the sensitivity of detection. In the present work, the effect
      of growth period on the sensitivity of an inhibitive assay for heavy metals using
      bacterial respiratory assay system based on the reduction of the water soluble
      tetrazolium dye MTT is reported. A silver-sensitive isolate was discovered to
      exhibit different sensitivities towards silver at different growth periods. An
      exponential decay model adequately described the inhibition due to silver.
      Analysis using ANOVA with post-hoc Tukey's test showed that the IC50 obtained by
      strain DRYS8 grown at the 12 hr- period in nutrient broth at 28 degrees C gave
      the lowest value compared to other growth periods. This study highlights the
      importance of taking into accounts growth conditions and age of culture in
      developing cellular-based bioassays.

PMID- 24665762
TI  - Assessment of heavy metals in suspended particulate matter in Moradabad, India.
AB  - Samples of suspended particulate matter (PM10) were collected from three
      different sites in Moradabad, India. The sampling was done concurrently twice a
      week during the period of April 2011-March 2012. Elemental concentration of PM10
      was analyzed using an Inductively Coupled Plasma Optical Emission
      Spectrophotometer (ICP-OES). The monthly mean concentration of PM10 (RSPM) ranged
      between 63-226 microgm(-3), which was higher than the permissible limit of 100
      microgm(-3) of National Ambient Air Quality Standards. The maximum concentration
      of Zn, Fe, Cu, Cr and Ni found in the Industrial area of the city was 21.24,
      18.43, 15.23, 0.41, 0.03 microgm(-3), respectively; whereas the maximum
      concentration of Pb (2.72 microgm(-3)) and Cd (0.20 microgm(-3)) was found in
      heavy density traffic area, denoted as commercial area. The study shows that high
      number of vehicles and the brassware industries are responsible for enhanced
      concentration of heavy metals in the Brass City.

PMID- 24665763
TI  - Comparative study of seasonal variation in bacterial flora concomitant with farm
      raised fingerlings of Cyprinus carpio at tarai region of Uttarakhand.
AB  - The bacterial infection is an important economic and limiting factor in intensive
      fish production. The present study focuses on investigation of the bacterial
      population associated with farmed common carp fingerlings, its environment and
      limnological quality of pond, during winter and summer season. It was found that
      the bacterial count in the pond sediment (6.40 cfu x 10(4)) was about 10 times
      higher in comparison of pond water (6.93 cfu x 10(3)). Further, the intestinal
      bacterial count was about 100 times higher (6.67 cfu x 10(5)) during winter and
      1000 times higher (2.33 cfu x 10(6)) during summer season in comparison to the
      surfacial skin of fish during winter and summer (3.39 and 8.87 cfu x 10(3)),
      respectively. The isolated bacteria were both Gram negative and Gram positive,
      mostly aerobic rods. Furthermore, the temperature showed a significant relation
      with the bacterial counts of pond water. In the summer season, higher bacterial
      counts (8.72 cfu x 10(3)) were recorded as compared to winter (5.13 cfu x 10(3)).
      The dominant bacteria isolated from the sample of pond water, pond sediment and
      fish were identified as Aeromonas hydrophila, Pseudomonas fluorescens,
      Pseudomonas sp., Flavobacter sp., Bacillus sp., Micrococcus sp., Corynebacterium
      sp. Moreover, the bacterial density was dependent on C:N values, and the optimum
      range of C: N ratio was found between 16-23, for the carp culture ponds. Among
      the isolated bacterial flora, the presence of strains which were well known for
      their probiotic properties suggested an autochthonous source for use in
      aquaculture. Further, analysis of various physico-chemical parameters of pond
      water revealed that they were within the suitable range for the freshwater fish
      culture throughout farming phase.

PMID- 24665764
TI  - A three year study on distribution and ecology of Anophelines in Thenzawl,
      Mizoram, India.
AB  - A systematic survey on Anopheline species abundance, bionomics and habitat
      preference was conducted for three years in Thenzawl, Mizoram. A scoop-net method
      was employed for larval collection and a local made killing-jar for adults. A
      total of 10 species Anopheles campestris (25.8%), An. nivipes (24.0%), An. vagus
      (20.6%), An. jamesii (15.1%), An. jeyporiensis (11.4%), An. maculatus (1.7%), An.
      philippinensis (0.7%), An. annularis (0.26%), An. sinensis (0.23%) and An.
      peditaeniatus (0.22%) were collected. The survey site having thick tall grasses,
      numerous rural-huts as residents, small to relatively larger ponds and very slow
      running water bodies well shaded from sunlight with floating aquatic plants
      provided the largest area for Anopheles larvae breeding and accounted for 40% of
      all Anopheles larva and 25.4% total Anopheles spp. collected. An. campestris
      (NSK01), maculatus (NSK04), philippinensis (NSK06), nivipes (NSK10) and
      jeyporiensis (NSK09) were strongly anthropogenic and endophagic while vagus
      (NSK18) and jamesii (NSK03) were found to be highly zoophilic and exophilic and
      An. peditaeniatus (NSK02), annularis (NSK07) and sinensis (NSK15) were found to
      be highly zoophilic. Because of its abundance and bionomics, An. campestris,
      jeyporiensis and nivipes may have played a role in malarial transmission
      throughout the year. This is the first study reported on Anopheline distribution
      and abundance in Thenzawl, Mizoram.

PMID- 24665765
TI  - Profiling of the dichloromethane-induced proteome expression changes.
AB  - A colorless volatile liquid dichloromethane (DCM) is used as solvents in chemical
      manufacturing processes. The major route of exposure is via inhalation and to a
      lesser extent through the skin and digestive tract. We investigated the effects
      of DCM on rats and analyzed their liver proteome expression changes.
      Approximately 1,100 protein spots that were detected by 2-dimensional gel
      electrophoresis showed reproducible abundance. Mass spectrometry based proteomics
      was used to characterize the changes in the liver proteome in response to DCM
      exposure. Consequently, 7 of these spots showed significant changes in expression
      level after DCM treatment. These proteins were 3 paralogues of glutathione S
      transferase, beta 1 globin, 2 hemoglobin beta-2 and alpha-2 globulin. Of these,
      the expression of alpha-2 globulin was also confirmed by western blot. The
      differential expression of these proteins might be caused by DCM exposure.

PMID- 24665766
TI  - Heat stress tolerance in relation to oxidative stress and antioxidants in
      Brassica juncea.
AB  - In the present study fifty genotypes of Brassica juncea were evaluated for heat
      stress tolerance in terms of biochemical components, in four day old seedlings.
      Heat shock was given at 45 degrees C for 4.5 hr and thereafter survival
      percentage, electrolyte leakage and chlorophyll content were estimated. Tolerant
      genotypes (10) registered survival greater than 65%, moderately tolerant (20)
      between 35-65% and susceptible (20) less than 35%. Electrolyte leakage was
      significantly (p < 0.001) higher in susceptible genotypes than in tolerant ones
      with respect to control seedlings. Chlorophyll content showed no significant
      variation among the tolerant, moderately tolerant and susceptible genotypes,
      although it registered a decline in response to heat stress. Lipid peroxidation,
      assessed by malondialdehyde (MDA) in stressed conditions was 4.66 (MDA g(-1) f.
      wt. of tissue) in tolerant genotypes, 7.44 (MDA g(-1) f. wt. of tissue) in
      susceptible genotypes and correlated significantly (r = 0.563) with electrolyte
      leakage. Increase in POD activity under heat stress was maximum in tolerant class
      with respect to control. CAT activity showed decrease after heat shock treatment
      in all the three classes but the decrease was 1.3 fold in tolerant genotypes as
      compared to 1.6 fold in susceptible genotypes. The non-enzymatic antioxidants
      glutathione and proline registered a significantly (< 0.01) high value in
      tolerant genotypes on heat shock treatment in comparison to susceptible genotypes
      corroborating the role of antioxidants in mitigating the effect of heat stress in
      Bjuncea. The antioxidants and proline seemed to play role in mitigating the
      effect of heat stress.

PMID- 24665767
TI  - Isolation and immunohistochemical identification of Flavobacterium psychrophilum
      from the tissue of catfish, Clarias batrachus.
AB  - This study deals with the identification of bacteria in paraffin embedded tissue
      of Indian catfish, Clarias batrachus experimentally infected with F.
      psychrophilum to ascertain it's precise role in the occurrence and state of
      carrier stage of coldwater disease in asymptomatic fishes. Significant (P < 0.05)
      mortality was recorded in C. batrachus of this region due to persistent
      occurrence of creamish/yellowish with non smooth edged colonies of rod shaped
      flexible gram negative bacterium, F. psychrophillum. Serodiagnosis made through
      polyclonal antiserum dilutions (raised against H antigen of Aqb Fb-6 isolate in
      rabbit) revealed that staining intensity of this bacterium was dilution dependent
      as tissue and smears treated with 1:300 and 1:500 antiserum dilutions conferred
      close relationship at immunofluorescence level with F. psychrophilum and stained
      deeply in the tissues and smear prepared from liver, kidney and intestine of
      experimentally infected C. batrachus. Result of this study would be helpful in
      identifying the fish pathogenic bacteria in carrier fish where mortality occurs
      without explicit clinical signs of disease.

PMID- 24665768
TI  - Quinalphos induced alteration in respiratory rate and food consumption of
      freshwater fish Cyprinus carpio.
AB  - Acute toxicity of commercial grade organophosphate insecticide, quinalphos (25%
      emulsified concentration) to common carp (Cyprinus carpio) was tested through
      bioassay. The acute toxicity of quinalphos to the fingerlings exposed for 96 hr
      was found to be 2.75 ppm. For sub lethal toxicity study, the fish were exposed to
      two concentration viz., 1/10th of LC50 (0.275 ppm) and 1/5th of LC50 (0.55 ppm)
      along with lethal concentration (2.75 ppm) as reference for 48 hr. The carps were
      under stress and mortality was insignificant in both sub lethal and lethal
      concentrations. However, considerable variation in respiration rate and food
      consumption rate was observed in both lethal and sublethal concentrations. The
      alteration observed in the physiological condition may be a consequence of
      impaired oxidative metabolism and elevated physiological stress by fish against
      quinalphos.

PMID- 24665769
TI  - Growth kinetics of a diesel-degrading bacterial strain from petroleum
      contaminated soil.
AB  - A diesel-degrading bacterium was isolated from a diesel-contaminated site in
      Selangor, Malaysia. The isolate was tentatively identified as Acinetobacter sp.
      strain DRY12 based on partial 16S rDNA molecular phylogeny and Biolog GN
      microplate panels and Microlog database. Optimum growth occurred from 3 to 5%
      diesel and the strain was able to tolerate as high as 8% diesel. The optimal pH
      that supported growth of the bacterium was between pH 7.5 to 8.0. The isolate
      exhibited optimal growth in between 30 and 35 degrees C. The best nitrogen source
      was potassium nitrate (between 0.6 and 0.9% (w/v)) followed by ammonium chloride,
      sodium nitrite and ammonium sulphate in descending order. An almost complete
      removal of diesel components was seen from the reduction in hydrocarbon peaks
      observed using Solid Phase Microextraction Gas Chromatography analysis after 10
      days of incubation. The best growth kinetic model to fit experimental data was
      the Haldane model of substrate inhibiting growth with a correlation coefficient
      value of 0.97. The maximum growth rate- micromax was 0.039 hr(-1) while the
      saturation constant or half velocity constant Ks and inhibition constant Ki, were
      0.387% and 4.46%, respectively. MATH assays showed that 75% of the bacterium was
      found in the hexadecane phase indicating that the bacterium was hydrophobic. The
      characteristics of this bacterium make it useful for bioremediation works in the
      Tropics.

PMID- 24665770
TI  - Effect of lead on growth, protein and biosorption capacity of Bacillus cereus
      isolated from industrial effluent.
AB  - A bacterial strain (Bacillus cereus) with the ability to grow under conditions of
      high concentrations of lead was isolated from the industrial effluent collected
      from Peenya Industrial Area, Bangalore. The effect of lead on growth, protein
      content and lead biosorption capacity of Bacillus cereus was investigated. The
      results revealed that with increase in lead concentration (100, 200, 300, 400 and
      500 mg I(-1)) there was a decrease in growth, protein content (10.6, 8.2, 6.7,
      3.8 and 1.9 mg g(-1) d. wt.) and lead biosorption (90.3, 57.8, 48.94, 31.3 and
      22.24%) Bacillus cereus, signifying toxic effect of lead on the bacterial strain.
      Plasmid DNA was isolated from Bacillus cereus to study its resistance mechanism.
      The size of the plasmid was approximately 33kb. Transformation results suggest
      that lead resistance gene may be present on the chromosomal DNA ratherthan the
      plasmid DNA as the transformants did not show lead resistance.

PMID- 24665771
TI  - Distribution and abundance of modern dinoflagellate cysts from Marmara, Aegean
      and Eastern Seas of Turkey.
AB  - Twenty-one surface sediment samples were collected from coastal areas of Turkey
      to determine horizontal distribution and abundance of the cysts. A total of 40
      dinoflagellate cyst types were identified and recorded in the range of 34 and
      31532 cyst g(-1) d.wt. in the sediments. The concentration of Lingulodinium
      machaerophorum, Polykrikos kofoidii, Quinquecuspis concreta, Dubridinium
      caperatum and Spiniferites bulloideus cysts dominated over other species.
      Although cysts of potentially toxic species of Alexandrium affine type and A.
      catenella/tamarense complex were found only in Izmir Bay. A. minutum type,
      Lingulodinium machaerophorum and Operculodinium centrocarpum were observed in the
      surface sediments of Marmara Sea and Fethiye Bay. The present study provides a
      database on the distribution and composition of dinoflagellate cysts in the
      Eastern Mediterranean sea coastal waters of Turkey where modern dinoflagellate
      cysts have been little studied.

PMID- 24665772
TI  - Black fly (Simulium sp) composition, daytime biting activity and possible
      onchocerciasis infection in north-east, India.
AB  - Pupal stages of Simulium were collected and identified from various breeding
      habitats of twelve locations in northeastern India. Simulium flies, while
      attempting to land on human were collected between 07:00-17:00 hrs to understand
      the biting pattern. Seven species belonging to three sub-genera, Eusimulium (1),
      Gomphostilbia (1) and Simulium (5) belonging genus Simulium were encountered. Out
      of total seven species recorded, S. (E) aureohirtum, S. (G) tenuistylum and S.
      (S) rufibasis were predominant and shared 30.3%, 29.9% and 27.6% of total
      collection. Stream breeding habitat contributed 47.3% of total catch and was
      found to be preferred breeding habitat (p < 0.0001). S. (S) christophersi and S.
      (G) tenuistylum were recorded for the first time from the northeastern region of
      India. Simuliids biting rhythm showed bimodal pattern and were more active during
      sunny day (p < 0.0001). Microscopic dissection of simuliids (n = 266) did not
      incriminate simuliids as vector of onchocerciasis.

PMID- 24665773
TI  - Neurotoxic impact of organophosphate pesticide phosphomedon on the albino rat.
AB  - Organophosphate pesticide phosphomedon was exposed to albino rat at a
      concentration of 35 ppm in the time interval of 30, 45 and 60 days. During the
      exposure period neurobehavioral symptoms such as reduce food intake, weight loss,
      increase water intake, low defecation frequency, increase locomotion frequency at
      high dose were observed. Locomotion frequency were less initially but higher in
      increasing dose concentration. The result was also different in both the sexes. A
      decrease social interaction and increase force swimming with increasing dose
      concentration, which was not significant as comparison to control. A significant
      histopathological changes observed in three dose concentrations. In 30 days
      phosphomedon exposure the nuclear shape changes to oval, pear shaped along with
      fibrosis, lipidosis, 45 days exposure showed the increase number of nucleus,
      Chromatolysis, inflammatory nucleus, pyknosis. In 60 days test group
      histopathological picture showed the swelling of cell body, lipidosis,
      demylination, necrosis in brain cells. Over all result indicated that due to
      impact of O. P pesticide phosphomedon a severe histopathological changes occurs
      which was distinctly observed in neurobehavioural changes.

PMID- 24665774
TI  - Effect of farm yard manure on chemical fractionation of cadmium and its bio
      availability to maize crop grown on sewage irrigated coarse textured soil.
AB  - Cadmium is a potentially toxic heavy metal that enters food chain from the soil
      through various anthropogenic sources. Availability of metal ions in contaminated
      soils can be reduced by the addition of organic amendments. In this study, effect
      of organic matter -farm yard manure (FYM) amendment on fractionation and
      availability of Cd to maize was evaluated. A green house experiment was conducted
      to determine the toxicity and uptake of Cd by maize in sandy loam soil with and
      without organic matter. Four levels of Cd (0, 10, 20 and 40 mg kg(-1) soil) and
      two levels of FYM (0 and 20 tonnes ha(-1)) with three replication in a completely
      randomized factorial design. Concentration of Cd in maize increased with
      increasing rate of Cd application. Application of organic matter increased the
      dry matter yield of maize while reduced the uptake of metal. All the fractions
      exhibited increase with Cd rates. The addition of organic amendment declined
      significantly the concentration of water soluble and exchangeable Cd, but
      increased the amounts of these metals into less mobile fractions (Fe/Mn oxide,
      organic matter and residual). Dominance of insoluble forms of Cd after the
      application of organic amendments may be ascribed to the increases of soil OM,
      pH, EC and available P contents which caused transformation or redistribution of
      the sorbed phases. This resulted in increasing Cd retention in the more
      persistent fractions with application of FYM at the expense of reductions in the
      loosely bound fractions. Thus FYM appears to be agronomically feasible way to off
      set the adverse effect of Cd toxicity.

PMID- 24665775
TI  - The effect of phosphate bio-fertilizer (Barvar-2) on the growth of marigold.
AB  - The present study was conducted to study the individual and combined effect of
      bio-fertilizer (Barvar-2) and chemical phosphate fertilizer on the floral quality
      of marigold (Tagetes erecta L.). A factorial experiment was carried out which
      consisted of two factors: i) inoculation of seed, root and seed + root with bio
      fertilizer (Barvar-2) and control; application of chemical phosphorus at 100 mg
      I(-1), 200 mg l(-1), 300 mg l(-1) and 400 mg l(-1) levels. In this study,
      flowering time, display life, fresh and dry weight of flower, available soil
      phosphorus, shoot phosphorus and carotenoid content were evaluated. Results
      showed that the combined effect of bio- and chemical fertilizer was insignificant
      (p < 1 and 5%) for most of the characteristics studied except for shoot
      phosphorus and carotenoid content in petals. The lowest time to flowering (64.67
      days) was obtained in seeds and transplant roots inoculation to bio-fertilizer x
      400 mg I(-1) P. Maximum display life (25.35), fresh weight (16.20 g), carotenoid
      content (3.903 mg g(-1) d. wt.) and concentration of P in shoots (0.352%) were
      observed in transplant roots inoculation to bio-fertilizer x 400 mg I(-1) P.

PMID- 24665776
TI  - Looking forward. Walter Reed Medical Center: caring for the nation's wounded.

PMID- 24665777
TI  - Medicaid expansion likely to affect the delivery of surgical care.

PMID- 24665778
TI  - Health policy program produces surgeon advocates and leaders.

PMID- 24665779
TI  - Preparing for implementation of the Physician Payments Sunshine Act.

PMID- 24665780
TI  - Gundersen Health System studies effect of modifier 22 on reimbursement for
      complex operations.

PMID- 24665781
TI  - PQRS reporting in 2014.

PMID- 24665782
TI  - Blameless or blameworthy errors: does your organization make a distinction?

PMID- 24665783
TI  - NTDB data points: Zero tolerance.

PMID- 24665784
TI  - Military surgeon reflects on service.

PMID- 24665785
TI  - The essence of professionalism.

PMID- 24665786
TI  - ACS should study sleep deprivation.

PMID- 24665787
TI  - The debate continues: ACS at the AMA House of Delegates.

PMID- 24665788
TI  - Health care leaders focus on emergency and trauma care at Nothern California IQ
      forum.

PMID- 24665789
TI  - Inline skating for balance and strength promotion in children during physical
      education.
AB  - Deficiencies in balance and strength are common in children and they may lead to
      injuries. This study investigated the effects of inline skating exercise on
      balance and strength performance in healthy children. Twenty 11-12-year-old
      children (8 girls, 12 boys) were assigned to an intervention (n = 10) or a
      control (n = 10) group. Participants in the intervention group underwent a 4-week
      inline skating program (2 times/week, 90 min. each) integrated in their physical
      education lessons. Balance and strength were measured using the Star Excursion
      Balance test and the countermovement jump test. As compared to the control group,
      the intervention group significantly improved balance (17-48%, Cohen's d = 0.00
      1.49) and jump height (8%, Cohen's d = 0.48). In children, inline skating is a
      safe, feasible (90% adherence rate), and effective program that can be integrated
      in physical education lessons to promote balance and strength.

PMID- 24665790
TI  - Effects of rest interval length on Smith machine bench press performance and
      perceived exertion in trained men.
AB  - This study compared two different rest intervals (RI) between sets of resistance
      exercise. Ten resistance-trained men (M age = 24.3, SD = 3.5 yr.; M weigh t= 80.0
      kg, SD = 15.3; M height = 1.75 m, SD = 0.04) performed five sets of Smith machine
      bench presses at 60% of one repetition maximum, either with 1.5 min. or 3 min. RI
      between sets. Their repetition performance, total training volume, velocity,
      fatigue, rating of perceived exertion, and muscular power were measured. All of
      these measures indicated that performance was significantly better and fatigue
      was significantly lower in the 3 min. RI as compared with the 1.5 min. RI, except
      the rating of perceived exertion which did not show a significant difference. A
      longer RI between sets promotes superior performance for the bench press.

PMID- 24665791
TI  - Moderating effect of regulatory focus on burnout and exercise behavior.
AB  - Applying Higgins' regulatory focus, which assumes that people pursue goals using
      means that match their self-regulatory motivation, the authors examined whether
      individual's promotion- or prevention-focused motivations in work would decrease
      participation in physical activity. Participants were 197 employees (163 men, 34
      women, M age = 39 yr.) in five different Taiwanese manufacturing firms. They
      responded to Copenhagen Burnout Inventory, the Regulatory Focus Questionnaire,
      and Exercise Behavior at two different times, 8-10 weeks apart. Promotion
      oriented regulatory focus significantly moderated the relationship between
      burnout and exercise, but prevention-oriented focus did not. BMI, blood pressure,
      cholesterol, and work hours contributed small but significant amounts of
      variance. A prevention focus was associated with more time for physical activity,
      even when participants were tired, supporting regulatory focus theory.

PMID- 24665792
TI  - Autonomy and structure can enhance motivation of volunteers in sport
      organizations.
AB  - The goal was better understanding of the motivational factors of volunteers in
      non-profit sport organizations. The roles of two factors provided by supervisors
      to their subordinates were examined: autonomy support, i.e., the encouragement of
      self-initiation and emphasis on choice rather than control, and structure, i.e.,
      the introduction of order, definite procedures, and rules. 489 sport volunteers
      (289 men, 200 women; M age = 31.2 yr., SD = 7.4) were administered questionnaires
      assessing their perceived autonomy support, structure, and motivation. Regression
      analysis indicated that perceived autonomy support predicted motivation.
      Structure also mediated the effect of perceived autonomy support on motivation.
      Supervisors of sport organizations should provide adequate structure for their
      volunteers.

PMID- 24665793
TI  - Efficacy of a cognitive program for improving the physical self-concept of
      university students.
AB  - The aim of this study was to test the efficacy of a 6-wk. educational program
      designed to improve physical self-concept, which was carried out in the
      classrooms of a university physical activity and sports faculty. The experimental
      group comprised 45 students (M age = 18.8 yr., SD = 1.5) and a control group (N =
      41; M age = 21.7 yr., SD = 1.2). The Autokontzeptu Fisikoaren Itaunketa/Physical
      Self-concept Questionnaire (AFI) was administered pre- and post-intervention,
      with a statistically significant increase being observed in the post-test scores
      of the experimental group on the General physical self-concept scale, as well as
      on the Condition, Attractiveness, and Strength scales. No statistically
      significant changes were observed in the control group.

PMID- 24665794
TI  - Duration of membership at sports centers and reasons for quitting.
AB  - Reasons for quitting membership at a sports center and their relation with socio
      demographic characteristics and duration of membership were investigated. 642
      individuals (55.4% men, 44.6% women), who had recently quit membership at a
      Spanish sports center, completed a questionnaire. There were significant
      differences in reasons for quitting on age, occupation, type of activities, and
      time spent on membership activities. The main reason was financial, regardless of
      the duration of membership.

PMID- 24665795
TI  - Sport participation motives of young Brazilian athletes.
AB  - The objective of this study was to identify the motives for sport participation
      in a sample of young Brazilian athletes according to sex, age, and training
      history. A total of 1,517 participants (714 girls, 803 boys) ages 12 to 18 years
      were included in the study. The Portuguese version of the Participation
      Motivation Questionnaire was used to identify motives for sport participation.
      The most important motives were Skill Development and Fitness, whereas the least
      important were Fun and Achievement/Status. Sex, age, type of sport, onset of
      training, duration of training, training volume, and competitive experience
      significantly influenced the motives for sport participation reported by the
      athletes. These results will contribute to establish intervention programs
      designed to reduce sport dropout rates among young athletes.

PMID- 24665796
TI  - Understanding mechanisms in transitive inferences: an eye-tracking study in
      Korean reading.
AB  - The current experiment examined the mechanism of relational information
      processing by assessing transitive inferences in different syntactic structures.
      More specifically, the current experiment focused on whether the demands of
      conscious inference processing interact with the difficulty of syntactic
      processing. This research used the eye-tracking method to investigate online
      processing mechanisms in complex sentences with transitive inference. Overall
      sentence reading times, accuracy rates of comprehension questions, and the two
      eye-movement measures of gaze duration and re-reading times were examined in 32
      participants. The results showed that inference processing demands affected
      overall reading times and accuracy rates, while syntactic processing demands did
      not have an effect on overall reading times or accuracy rates. The results of the
      eye-tracking measures showed that syntactic processing demands affected gaze
      duration, while the inference processing demand affected re-reading times.
      Apparently, the difficulty of inference processing was not affected by the
      surface form of a sentence. The results of this study suggested that basic
      processes of sentence interpretation share resources with other cognitive
      processes such as inference.

PMID- 24665797
TI  - Relations among visual strategies, force fluctuations, and attention during a
      force-matching task.
AB  - Greater understanding of how people use visual information to minimize force
      fluctuations provides critical insight into visuomotor processing. Visual
      strategies were examined during a force-matching task with different feedback
      displays. When only vertical feedback was provided, young healthy participants (N
      = 20, 9 men) fixated their gaze centrally. When vertical and horizontal visual
      feedback was provided, participants performed saccades to maintain gaze near the
      leading edge of the force trace. Performance on a separate attention task
      assessed visual and motor attention capabilities in the same participants.
      Selecting the correct saccade trajectory on the attention task was positively
      correlated with measures predicting performance on the force-matching task.
      Optimal visual strategies, combined with motor attention, may contribute to
      minimizing pinch force variability at low force.

PMID- 24665798
TI  - Psychomotor performance of elite volleyball players during a game.
AB  - Prior studies have found that reaction time and movement time increase with
      fatigue (measured by blood lactate concentration) in laboratory situations. The
      study tested whether these relationships occurred for reaction time and movement
      time of elite volleyball players during a training game. Components of the
      players' psychomotor performance (reaction time, movement time) and physiological
      parameters (heart rate, blood lactate concentration) were analyzed. Fourteen
      male, adolescent volleyball players participated in the study. Reaction time and
      movement time were measured with the Optojump measurement system during the game
      in off-the-court periods. All measurements were performed during a pre-game test
      and during each of the four sets of the game. During Set 1, players' reaction
      time decreased significantly compared with the pre-game test indicating a likely
      warm-up effect. Blood lactate concentration increased significantly across sets.
      However, the players' reaction times remained constant across sets. The studied
      players did not exceed the psychomotor fatigue threshold anytime during the
      entire game. These findings indicate that the amount of training (20 hours a
      week) done by elite players is sufficient to prevent threshold fatigue levels
      that create significant decreases in psychomotor performance.

PMID- 24665799
TI  - Relations among dynamic balance tests and a coordination test using center of
      pressure to pursue a randomly moving target.
AB  - The CFP (center of foot pressure) Tracking Test, in which participants pursue a
      randomly moving target using CFP, is performed in standing position similar to
      the dynamic balance board and bass dynamic balance tests. The relations among the
      results of these three tests were examined in 30 young, healthy participants. No
      significant sex differences were observed between tests. Moderate correlations
      were observed between the results of the CFP Tracking Test and the balance tests,
      but not between the two balance tests. The CFP Tracking Test was related to the
      two balance tests, but evaluates unique abilities other than balance ability.

PMID- 24665800
TI  - Relationship between general and specific coordination in 8- to 17-year-old male
      basketball players.
AB  - The purpose of the present study was to investigate the relationships between
      general coordination, sport-specific coordination, and sport-specific fitness of
      8- to 17-year-old male basketball players. 312 males with training experience
      ranging from one year in the 8-year-old cohort up to 10 years for the 17-year
      olds performed basketball-specific fitness (20 m sprint, Illinois,
      countermovement jump), general coordination (20 m run with three obstacles), semi
      basketball-specific coordination (20 m sprint dribbling two balls,
      countermovement jump with arm swing) and basketball-specific coordination
      (Illinois ball dribbling) tests. There were moderate to large correlations
      between the results of both general and basketball-specific coordination with the
      results of most basketball-specific coordination tests in all age groups.
      Correlations between general and basketball-specific coordination were large in
      four age groups (11-14 yr., r = .52 to r = .76), moderate in five groups (8-10,
      15 & 16 yr., r = .37 to r = .46), while not significant in the 17-year-olds.
      These results suggest that the importance of general coordination for sport
      specific skills improvements during a sports-specific skill acquisition phase,
      remains high at the skill refinement phase, and decreases when sport-specific
      skills have been mastered to near-perfection.

PMID- 24665801
TI  - Relations between BMI, body mass and height, and sports competence among
      participants of the 2010 Winter Olympic Games: does sport metabolic demand
      differentiate?
AB  - This study characterizes the athletes participating in the 2010 Winter Olympic
      Games in terms of body height, body mass and BMI. The studied sample consisted of
      athletes in the top 20 places of each of 14 sports disciplines (1460 cases). Data
      on the athletes' age, height, body mass, and sports specialization were obtained
      from the Olympic Games' official website and from the International Ski
      Federation. The sampled athletes were grouped according to the predominant type
      of energy metabolism during competition. The anaerobic-glycolytic disciplines,
      such as cross-country sprint, figure skating, short track, and speed skating
      (500, 1000 and 1500 m), were found to have the youngest female athletes: 25.0 yr.
      (SD = 4.7). In the endurance sports (aerobic and aerobic-anaerobic), the female
      athletes were the oldest, being respectively 28.6 yr. (SD = 4.9) and 28.1 yr. (SD
      = 4.5) old. In the speed disciplines (anaerobic-alactic), the female athletes
      were the tallest (M = 172 cm; SD = 8.3). The male athletes in the anaerobic
      alactic sports were the tallest (M = 181.8 cm, SD = 6.7) and those in the
      anaerobic-glycolytic sports were the shortest (M = 179.2 cm, SD = 6.7). The large
      differences in body mass among the groups of athletes, which appear to be related
      to the predominant type of metabolism during competition, show that this
      parameter is partly correlated with the level of sports competence, but only in
      disciplines where the athletes need larger muscle mass. The largest average
      values of BMI were found for males and females in the anaerobic-alactic group.

PMID- 24665802
TI  - Enlargement of perceived target size: intentional or natural?
AB  - This study used a soccer context to examine the relations between scores and
      judgments of goal sizes. In Experiment 1, 18 participants (4 women, 14 men; M age
      = 21.9 yr., SD = 0.9) kicked balls into 5 goals of different sizes. Participants'
      estimates of the goal size correlated positively with their scores. In Experiment
      2, 17 participants (3 women, 14 men; M age = 22.1 yr., SD = 1.0) kicked the balls
      either from a standing position or while running. Participants' estimates of the
      goal sizes were higher when they were running. The enlargement of perceived goal
      size was seemingly related to scoring, and was scaled by the running action.
      Experiments reinforced the notion of affordance-based control. Differing views
      from Oriental philosophy and psychology were discussed.

PMID- 24665803
TI  - Psychophysical assessments of sourness in citric acid-ethanol mixtures.
AB  - The effect of ethanol in modulating the intensity and duration of the perceived
      sourness induced by citric acid was studied. Magnitude Estimation-Converging
      Limits method was applied to rate the sourness of seven solutions (3-70 mM) of
      citric acid in aqueous solution presented alone and mixed with 8% V/V or 15% V/V
      ethanol. Dynamic sourness ratings of 5, 15, and 45 mM citric acid alone and mixed
      with the same two ethanol levels were assessed by the Time Intensity Method (TI).
      Results were consistent with both methods. Sourness changed with citric acid
      concentration and ethanol levels. From TI measurements, a similar interactive
      pattern was obtained for parameters as duration, area under the curve, peak and
      average intensity.

PMID- 24665804
TI  - Effect of resistance exercise performed to volitional failure on ratings of
      perceived exertion.
AB  - The purpose of this investigation was to assess the effect of resistance exercise
      performed to volitional failure on ratings of perceived exertion (RPE) using
      power as an indication of fatigue. 12 male participants (M age = 21.9 yr., SD =
      1.3) performed one set of back squats at three different intensities (50%, 70%,
      and 90% of one repetition maximum) for both a pre-determined number of
      repetitions (3) and to volitional failure. RPE was significantly different
      between sets at 50%, 70%, and 90% when performed to a pre-determined number of
      repetitions, but not during volitional failure. A decrease in power between the
      first and the last repetitions in the volitional failure sets suggests that
      fatigue may confound the relationship between RPE and intensity.

PMID- 24665806
TI  - Processing female and male voices: a word spotting experiment.
AB  - Several previous studies showed that synthetic vowel identification is more
      difficult for voices with a high f0 (the lowest frequency that defines voice
      pitch), but it is not clear whether this means that female voices, which
      generally have a higher f0, are processed more slowly than male voices. A word
      spotting experiment was conducted with 25 French native listeners (8 men, 17
      women; M age = 27.6 yr., SD = 10.8). Words produced by four male and four female
      speakers were played to the participants. Their task was to press a button every
      time they identified the target word "etage." Response times were collected and
      compared in four different conditions: male voice preceded by male voices, female
      voice preceded by female voices, male voice preceded by female voices, and female
      voice preceded by male voices. Results showed that both sexes' voices were
      processed equally fast. Moreover, no significant correlation was found between
      mean f0 of the target word and response time. Nevertheless, when a target word
      produced by a male speaker occurred after several words produced by a female
      speaker (or vice-versa) the listener's RT decreased, suggesting that male and
      female voices are processed as two different entities.

PMID- 24665805
TI  - Association between different phases of menstrual cycle and body image measures
      of perceived size, ideal size, and body dissatisfaction.
AB  - The association between phases of the menstrual cycle and body image was
      investigated. 44 university women (M age = 23.3 yr., SD = 4.7) judged their
      perceived and ideal body size, and body dissatisfaction was calculated at each
      phase of the menstrual cycle, including premenstrual, menstrual, and
      intermenstrual. Participants selected one of nine figural drawings ranging from
      very thin to obese that represented their perceived size and ideal size. Body
      dissatisfaction was measured as the absolute difference between scores on
      perceived and ideal figural drawings. During each menstrual phase, anthropometric
      measures of weight, height, body mass index, circumference of waist and abdomen,
      and body composition were taken. There were no significant differences in any
      anthropometric measures between the three menstrual cycle phases. Perceived body
      size and body dissatisfaction were significantly different between menstrual
      phases, with the largest perceived body size and highest body dissatisfaction
      occurring during the menstrual phase. Ideal body size did not differ between
      menstrual phases, although participants desired a significantly smaller ideal
      size as compared to the perceived size.

PMID- 24665807
TI  - Executive functions as predictors of visual-motor integration in children with
      intellectual disability.
AB  - The goal of this study was to assess the relationship between visual-motor
      integration and executive functions, and in particular, the extent to which
      executive functions can predict visual-motor integration skills in children with
      intellectual disability. The sample consisted of 90 children (54 boys, 36 girls;
      M age = 11.3 yr., SD = 2.7, range 7-15) with intellectual disabilities of various
      etiologies. The measure of executive functions were 8 subscales of the Behavioral
      Rating Inventory of Executive Function (BRIEF) consisting of Inhibition,
      Shifting, Emotional Control, Initiating, Working memory, Planning, Organization
      of material, and Monitoring. Visual-motor integration was measured with the
      Acadia test of visual-motor integration (VMI). Regression analysis revealed that
      BRIEF subscales explained 38% of the variance in VMI scores. Of all the BRIEF
      subscales, only two were statistically significant predictors of visual-motor
      integration: Working memory and Monitoring. Possible implications of this finding
      are further elaborated.

PMID- 24665809
TI  - Development and use of an observation tool for active gaming and movement (OTAGM)
      to measure children's movement skill components during active video game play.
AB  - This article presents a direct observational tool for assessing children's body
      movements and movement skills during active video games. The Observation Tool of
      Active Gaming and Movement (OTGAM) was informed by the Test of Gross Motor
      Development-2. 18 elementary school children (12 boys, 6 girls; M age = 6.1 yr.,
      SD = 0.9) were observed during Nintendo Wii game play. Using the OTAGM,
      researchers were able to capture and quantify the children's body movements and
      movement skills during active play of video games. Furthermore, the OTAGM
      captured specific components of object control skills: strike, throw, and roll.
      Game designers, health promotion practitioners, and researchers could use this
      information to enhance children's physical activity and movement skills.

PMID- 24665808
TI  - Evaluation of the relative contribution of peripheral and focal vision to
      proprioceptive differentiation of underfoot inversion angles in young elite
      athletes.
AB  - Different visual conditions during proprioceptive testing have the potential to
      mask clinically meaningful differences in proprioceptive acuity, and must be
      understood in order to improve testing accuracy. This study compared the
      proprioceptive acuity achieved in estimating underfoot surface angles when
      looking ahead vs looking down during an active stepping task. 40 athletes from
      national development squads (23 male, 17 female, M age = 16 yr.) judged the
      inversion angle of a footplate when stepping onto and across it. 19 participants
      were permitted to briefly look down and see the footplate before stepping onto
      it, while 21 looked ahead and saw the footplate only in peripheral vision as they
      walked across. Looking down before stepping contributed to higher proprioceptive
      acuity scores. These results indicate that during a stepping task, a short
      opportunity to assess ground angle with focal vision supports the peripheral
      sensory receptors in proprioceptive acuity to a greater extent than peripheral
      vision alone.

PMID- 24665810
TI  - Pilot study on infant swimming classes and early motor development.
AB  - Alberta Infant Motor Scale (AIMS) scores were examined before and after four
      months of swimming classes in 12 babies (ages 7 to 9 mo.) assigned to
      Experimental (n = 6) and Control (n = 6) groups matched on age and developmental
      status. Infants from both groups improved their developmental status from pre- to
      post-test; the Experimental group improved on mean percentile rank. The sample
      size and the discriminative power of the AIMS do not allow conclusive judgments
      on these group differences, hence on the effect of infant swimming classes.
      Nevertheless, a number of recommendations are made for future studies on the
      effect of swimming classes on infant motor development.

PMID- 24665811
TI  - Influence of a health-related physical fitness model on students' physical
      activity, perceived competence, and enjoyment.
AB  - This study was designed to explore the effects of a health-related physical
      fitness physical education model on students' physical activity, perceived
      competence, and enjoyment. 61 students (25 boys, 36 girls; M age = 12.6 yr., SD =
      0.6) were assigned to two groups (health-related physical fitness physical
      education group, and traditional physical education group), and participated in
      one 50-min. weekly basketball class for 6 wk. Students' in-class physical
      activity was assessed using NL-1000 pedometers. The physical subscale of the
      Perceived Competence Scale for Children was employed to assess perceived
      competence, and children's enjoyment was measured using the Sport Enjoyment
      Scale. The findings suggest that students in the intervention group increased
      their perceived competence, enjoyment, and physical activity over a 6-wk.
      intervention, while the comparison group simply increased physical activity over
      time. Children in the intervention group had significantly greater enjoyment.

PMID- 24665812
TI  - Relationships of Borg's RPE 6-20 scale and heart rate in dynamic and static
      exercises among a sample of young Taiwanese men.
AB  - The objective of this study was to assess the relationship between the scores
      collected from Borg's rating of perceived exertion (RPE) scale and the heart
      rates (HR) of young Taiwanese men. Three exercises types (dynamic, partially
      dynamic, and static) were performed by 12 participants (six were familiar with
      Borg's scale and 6 were unfamiliar) under nine test conditions of three load
      levels for each exercise. The effect of familiarity on the relationship between
      RPE and HR was also examined. The results showed that the familiarity of the
      participants regarding the Borg's scale did not affect the scores. The
      relationship between Borg's RPE 6-20 scale and the HR values during dynamic
      exercise was described by the regression equation HR = 8.88 x RPE + 38.2
      (beats/min). The HR had lower correlations with RPE values when the participants
      performed both partially dynamic and static exercises. The findings may serve as
      a reference when using Borg's RPE scale to evaluate the physical exertion of
      young Taiwanese men.

PMID- 24665813
TI  - The nature and research on hypnosis and placebo effect.

PMID- 24665814
TI  - Placebo versus "standard" hypnosis rationale: attitudes, expectancies, hypnotic
      responses, and experiences.
AB  - In this study participants were provided with either the standard rationale that
      accompanies the Harvard Group Scale of Hypnotic Susceptibility: A (Shor & Orne,
      1962) or a rationale that presented hypnosis as a nondeceptive placebo,
      consistent with Kirsch's (1994) sociocognitive perspective of hypnosis. The
      effects of the placebo and standard rationales were highly comparable with
      respect to hypnotic attitudes; prehypnotic expectancies; objective, subjective,
      and involuntariness measures of hypnotic responding; as well as a variety of
      subjective experiences during hypnosis, as measured by the Phenomenology of
      Consciousness Inventory (Pekala, 1982). Differences among correlations were not
      evident when measures were compared across groups. However, indices of hypnotic
      responding were correlated with attitudes in the hypnosis but not the placebo
      condition, and, generally speaking, the link between subjective experiences
      during hypnosis and measures of hypnotic responding were more reliable in the
      placebo than the hypnosis group. Researcher findings are neutral with respect to
      providing support for altered state versus sociocognitive models of hypnosis.

PMID- 24665815
TI  - The role of tactile support in arm levitation.
AB  - How many persons need tactile support a la Milton H. Erickson to achieve arm
      levitation during hypnosis? How do these differ from those who do not need it?
      Hypnotic arm levitation was suggested three times consecutively to 30 medium
      suggestible students. Sixteen succeeded without any tactile support; 7 needed it
      one or two times; 5 needed it every time; and 2 achieved no arm levitation at
      all. Participants without any tactile support went more quickly into deeper
      hypnosis, experienced more involuntariness, less effort, and had higher
      electrodermal activity. This greater physiological activity seems necessary for
      hypnotic arm levitation as a form of "attentive hypnosis" in contrast to
      "relaxation hypnosis." A change in verbal suggestion from "imagine a helium
      balloon" to "leave levitation to your unconscious mind" revealed no differences.
      Several issues resulting from this exploratory arm levitation study are
      discussed. The idea of different proprioceptive-kinesthetic abilities is
      introduced and the profound need of co-creating an individual suggestion is
      emphasized.

PMID- 24665816
TI  - I-95 phobia treated with hypnotic systematic desensitization: a case report.
AB  - Systematic desensitization and hypnosis mediated therapy share empirical evidence
      of efficacy in the treatment of specific phobias. However, a review of the
      literature indicated there is limited documentation in the employment of these
      modalities for treating driving related phobias (DRP). This article reports on
      the use of hypnosis aided systematic desensitization (HASD) in the successful
      treatment of a case of non-accident related driving phobia, specifically
      manifested on Interstate 95 (I-95). The treatment consisted of 6 office sessions
      of HASD along with 14 in-vivo sessions where the patient performed multiple
      exposures/rehearsals of the behaviors that had been successfully mastered at the
      office visits. The results indicated that this patient with case of (DRP) was
      able to resume travel on I-95 at conclusion of treatment. The patient was symptom
      free at follow up 6 months later.

PMID- 24665817
TI  - Symptoms as solutions: hypnosis and biofeedback for autonomic regulation in
      autism spectrum disorders.
AB  - The Autonomic Dysregulation Theory of autism posits that a phylogenetically early
      autonomic defect leads to overarousal and impairments in language and social
      engagement. Cognitive rigidity and repetitive behaviors manifest as mitigating
      efforts. Focusing on the implications of this premise may provide more productive
      therapeutic approaches than existing methods. It suggests that self-regulation
      therapy using hypnosis and biofeedback should be highly effective, especially for
      young people. Hypnotic strategies can utilize restrictive repetitive behaviors in
      trance as resources for comfort and control. Biofeedback training can be tailored
      to focus on autonomic regulation. The authors develop this theory and describe
      methods of integrating hypnosis and biofeedback that have been therapeutic for
      people with autism. Directions for future research to validate this approach are
      discussed.

PMID- 24665818
TI  - A review of the history of hypnosis through the late 19th century.
AB  - A review of the history of hypnosis through the late 19th century is provided in
      this article. The author offers an important review for practitioners of hypnosis
      preparing to take diplomate board examinations. Clinicians will also be enabled
      to trace the evolution of clinical methods, principles, and techniques.

PMID- 24665819
TI  - Photophysical and photochemical trends in tricarbonyl rhenium(I) N-heterocyclic
      carbene complexes.
AB  - A family of tricarbonyl Re(I) complexes of the formulation fac-[Re(CO)3(NHC)L]
      has been synthesized and characterized, both spectroscopically and structurally.
      The NHC ligand represents a bidentate N-heterocyclic carbene species where the
      central imidazole ring is substituted at the N3 atom by a butyl, a phenyl, or a
      mesityl group and substituted at the N1 atom by a pyridyl, a pyrimidyl, or a
      quinoxyl group. On the other hand, the ancillary L ligand alternates between
      chloro and bromo. For the majority of the complexes, the photophysical properties
      suggest emission from the lowest triplet metal-to-ligand charge transfer states,
      which are found partially mixed with triplet ligand-to-ligand charge transfer
      character. The nature and relative energy of the emitting states appear to be
      mainly influenced by the identity of the substituent on the N3 atom of the
      imidazole ring; thus, the pyridyl complexes have blue-shifted emission in
      comparison to the more electron deficient pyrimidyl complexes. The quinoxyl
      complexes show an unexpected blue-shifted emission, possibly occurring from
      ligand-centered excited states. No significant variations were found upon
      changing the substituent on the imidazole N3 atom and/or the ancillary ligand.
      The photochemical properties of the complexes have also been investigated, with
      only the complexes bound to the pyridyl-substituted NHC ligands showing
      photoinduced CO dissociation upon excitation at 370 nm, as demonstrated by the
      change in the IR and NMR spectra as well as a red shift in the emission profile
      after photolysis. Temperature-dependent photochemical experiments show that CO
      dissociation occurs at temperatures as low as 233 K, suggesting that the Re-C
      bond cleaves from excited states of metal-to-ligand charge transfer nature rather
      than thermally activated ligand field excited states. A photochemical mechanism
      that takes into account the reactivity of the complexes bound to the pyridyl-NHC
      ligand as well as the stability of those bound to the pyrimidyl- and quinoxyl-NHC
      ligands is proposed. 

PMID- 24665820
TI  - Stacked quantum dot embedded silica film on a phosphor plate for superior
      performance of white light-emitting diodes.
AB  - Application of quantum dots as a color converter in white light-emitting diodes
      (WLEDs) has been highly restrained because of its lower stability under the
      operating conditions of LEDs. The feasibility of using quantum dots in WLEDs has
      been studied and demonstrated by developing a non-conventional packing technique.
      Multiple core shell CuInS2/ZnS quantum dots were coated by silica, and the silica
      coated quantum dots were dispersed in ethoxylated trimethylolpropane triacrylate
      to form a color conversion film. This along with phosphor in a glass plate made
      of Y3Al5O12:Ce(3+) phosphor was stacked in different configurations, and its
      effect on color rendering of WLEDs was studied. In addition, the configuration
      developed here protects the color converter from thermal strain and moisture. 

PMID- 24665821
TI  - Hydrogen sulfide upregulates glutamate-cysteine ligase catalytic subunit,
      glutamate-cysteine ligase modifier subunit, and glutathione and inhibits
      interleukin-1beta secretion in monocytes exposed to high glucose levels.
AB  - Glutathione (GSH) deficiency and interleukin-1beta (IL-1beta) upregulation are
      linked to the progression of vascular inflammation and atherosclerosis. The
      consumption of sulfide-rich vegetables is known to lower the risk of
      atherosclerosis. This study examined the hypothesis that hydrogen sulfide (H2S)
      upregulates the glutamate-cysteine ligase catalytic subunit (GCLC) and GSH and
      inhibits IL-1beta in a monocyte cell model. U937 monocytes were supplemented with
      H2S (0-12.5 MUM) for 2 hr and then exposed to a control or high glucose (HG, 25
      mM) for 22 hr. Levels of GCLC and glutamate-cysteine ligase modifier subunit
      (GCLM) expression were determined by western blotting and GSH using high
      performance liquid chromatography (HPLC), and IL-1beta using enzyme-linked
      immunoassay (ELISA). H2S significantly (P<0.05) upregulated expression of GCLC
      and GCLM, and formation of GSH, and inhibited IL-1beta secretion in controls and
      HG-treated monocytes. This is the first demonstration of H2S upregulation of GCLC
      and GSH and inhibition of IL-1beta levels, which may be what mediates the
      beneficial effects of H2S-rich compounds in mitigating the pathogenesis of
      metabolic syndrome and atherosclerosis.

PMID- 24665822
TI  - Hemicarceplexes modify the solubility and reduction potentials of C60.
AB  - A highly stable C60-incarcerated hemicarceplex, which retains its molecular
      integrity after heating at 523 K in air for at least 3 h, significantly increases
      the solubility of C60 in nonpolar solvents and increases the reduction potentials
      of the entrapped fullerene. Modification with [(eta(5)-C5Me5)Ru(II)](+)
      dramatically increases the solubility of this hemicarceplex in polar, protic
      solvents (e.g., MeOH).

PMID- 24665823
TI  - The innate immune response to HIV-1: to sense or not to sense.
AB  - The immune responses to viruses provide a means to quickly alert the host to the
      presence of an invader, activating a range of intrinsic and adaptive antiviral
      mechanisms. Several research groups have made advances in understanding the
      innate immune response to HIV-1, although their findings differ. Some
      investigators find that the virus slips under the radar of the pattern
      recognition receptors that sense viruses by co-opting host factors that restrict
      accessibility of the viral nucleic acids, while others find that the virus is
      sensed and activates a type-I interferon response. This article reviews the
      recent findings and discusses the similarities and differences. 

PMID- 24665824
TI  - Rapid qualitative and quantitative analyses of proanthocyanidin oligomers and
      polymers by UPLC-MS/MS.
AB  - This paper presents the development of a rapid method with ultraperformance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the qualitative
      and quantitative analyses of plant proanthocyanidins directly from crude plant
      extracts. The method utilizes a range of cone voltages to achieve the
      depolymerization step in the ion source of both smaller oligomers and larger
      polymers. The formed depolymerization products are further fragmented in the
      collision cell to enable their selective detection. This UPLC-MS/MS method is
      able to separately quantitate the terminal and extension units of the most common
      proanthocyanidin subclasses, that is, procyanidins and prodelphinidins. The
      resulting data enable (1) quantitation of the total proanthocyanidin content, (2)
      quantitation of total procyanidins and prodelphinidins including the
      procyanidin/prodelphinidin ratio, (3) estimation of the mean degree of
      polymerization for the oligomers and polymers, and (4) estimation of how the
      different procyanidin and prodelphinidin types are distributed along the
      chromatographic hump typically produced by large proanthocyanidins. All of this
      is achieved within the 10 min period of analysis, which makes the presented
      method a significant addition to the chemistry tools currently available for the
      qualitative and quantitative analyses of complex proanthocyanidin mixtures from
      plant extracts. 

PMID- 24665825
TI  - Treatment of a Patient With Implant Failure and Jaw Osteonecrosis: Successful
      Retreatment Using Implants.

PMID- 24665827
TI  - Inhibition of platelet activation could decrease thrombotic events in
      hemodialysis PF4/H antibody-positive patients.
AB  - BACKGROUND: Platelet factor 4/heparin (PF4/H) antibody detection is widely used
      to evaluate the risk of thrombosis in patients undergoing hemodialysis (HD). Most
      patients who are PF4/H-antibody-positive can survive thrombosis, but the reason
      has not been clarified. In addition, no valid preventive methods for thrombosis
      in patients undergoing HD have been confirmed. METHODS: A single-center, semi
      randomized controlled study was designed. In total, 157 patients fulfilled the
      inclusion criteria and participated. Patients were first divided according to
      PF4/H antibody detection and then subdivided randomly according to different anti
      platelet agent descriptions. RESULTS: (1) PF4/H antibody-positive patients
      suffered a significantly higher incidence of thrombosis than those who were
      antibody-negative; (2) PF4/H antibody-positive patients who survived a thrombosis
      manifested a significantly longer bleeding time and decreased maximum percentage
      of platelet aggregation inhibition; (3) aspirin and clopidogrel decreased the
      incidence of thrombosis in PF4/H antibody-positive patients by inhibiting
      platelet activation. CONCLUSION: The PF4/H antibody was effective for prediction
      of the risk of thrombosis, except in patients with dysfunctional platelets;
      aspirin manifested effects similar to clopidogrel in terms of prevention of
      thromboses in PF4/H antibody-positive patients, but costs much less and is
      therefore recommended.

PMID- 24665829
TI  - Review article: evidence for the role of gut microbiota in irritable bowel
      syndrome and its potential influence on therapeutic targets.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal
      disease with a substantial social and economic burden. Treatment options remain
      limited and research on the aetiology and pathophysiology of this multifactorial
      disease is ongoing. AIM: To discuss the potential role of gut microbiota in the
      pathophysiology of IBS and to identify possible interactions with
      pathophysiologic targets in IBS. METHODS: Articles were identified via a PubMed
      database search ['irritable bowel syndrome' AND (anti-bacterial OR antibiotic OR
      flora OR microbiota OR microflora OR probiotic)]. English-language articles were
      screened for relevance. Full review of publications for the relevant studies was
      conducted, including additional publications that were identified from individual
      article reference lists. RESULTS: The role of gut microbiota in IBS is supported
      by varying lines of evidence from animal and human studies. For example, post
      infectious IBS in humans is well documented. In addition, certain probiotics and
      nonsystemic antibiotics appear to be efficacious in the treatment of IBS.
      Mechanisms involved in improving IBS symptoms likely go beyond mere changes in
      the composition of the gut microbiota, and accumulating animal data support the
      interplay of microbiota with other IBS targets, such as the gut-brain axis,
      visceral hypersensitivity, mucosal inflammation and motility. CONCLUSION: The
      role of the gut microbiota is still being elucidated; however, it appears to be
      one of several important factors that contributes to the aetiology and
      pathophysiology of the irritable bowel syndrome.

PMID- 24665828
TI  - Effect of salinity on oxygen consumption in fishes: a review.
AB  - The effect of salinity on resting oxygen uptake was measured in the perch Perca
      fluviatilis and available information on oxygen uptake in teleost species at a
      variety of salinities was reviewed. Trans-epithelial ion transport against a
      concentration gradient requires energy and exposure to salinities osmotically
      different from the body fluids therefore imposes an energetic demand that is
      expected to be lowest in brackish water compared to fresh and sea water. Across
      species, there is no clear trend between oxygen uptake and salinity, and
      estimates of cost of osmotic and ionic regulation vary from a few per cent to
      >30% of standard metabolism. 

PMID- 24665830
TI  - The determination of optimal initial tension in rat coronary artery using wire
      myography.
AB  - The aim of the present study was to determine the optimal initial tension, i.e.
      initial stretch for rat coronary artery when using the multi-wire myograph
      system. We used the normalization procedure to mimic physiological conditions and
      to stretch the coronary arterial segments to normalized internal circumference
      (IC(1)). It is determined the internal circumference when the vessel relaxed
      under a transmural pressure of 100 mm Hg (IC(100)), and the IC(1) is calculated
      by multiplying the IC(100) by a factor k. The impact of different factor k on the
      initial stretch and agonist-induced tension of coronary arteries were
      investigated. The results showed that the maximal agonist-induced tension was
      achieved at the factor k value of 0.90 and the initial stretch tension was given
      1.16+/-0.04 mN/mm. The most appropriate factor k value was 0.90-0.95 and the most
      appropriate initial tension was 1.16-1.52 mN/mm. The equilibration time of the
      coronary artery segments should be at least 1.0 h. In the same optimal initial
      tension, the agonist-induced tension increased as equilibration time lengthened. 

PMID- 24665826
TI  - Movers and shakers: cell cytoskeleton in cancer metastasis.
AB  - Metastasis is responsible for the greatest number of cancer deaths. Metastatic
      disease, or the movement of cancer cells from one site to another, is a complex
      process requiring dramatic remodelling of the cell cytoskeleton. The various
      components of the cytoskeleton, actin (microfilaments), microtubules (MTs) and
      intermediate filaments, are highly integrated and their functions are well
      orchestrated in normal cells. In contrast, mutations and abnormal expression of
      cytoskeletal and cytoskeletal-associated proteins play an important role in the
      ability of cancer cells to resist chemotherapy and metastasize. Studies on the
      role of actin and its interacting partners have highlighted key signalling
      pathways, such as the Rho GTPases, and downstream effector proteins that, through
      the cytoskeleton, mediate tumour cell migration, invasion and metastasis. An
      emerging role for MTs in tumour cell metastasis is being unravelled and there is
      increasing interest in the crosstalk between key MT interacting proteins and the
      actin cytoskeleton, which may provide novel treatment avenues for metastatic
      disease. Improved understanding of how the cytoskeleton and its interacting
      partners influence tumour cell migration and metastasis has led to the
      development of novel therapeutics against aggressive and metastatic disease.
      LINKED ARTICLES: This article is part of a themed section on Cytoskeleton,
      Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view
      the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-24.

PMID- 24665831
TI  - Melatonin in the oral cavity: physiological and pathological implications.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this article was to summarize what is
      known about the function of melatonin in the oral cavity. MATERIAL AND METHODS:
      Databases were searched for the relevant published literature to 30 November,
      2013. The following search items were used in various combinations: melatonin,
      gingiva, periodontium, inflammation, herpes, alveolar bone, periodontal ligament,
      dental implants, xerostomia, methacrylate, chlorhexidine, cancer. The literature
      uncovered is summarized herein. RESULTS: Salivary melatonin levels exhibit a
      circadian rhythm with highest values at night. Melatonin has both receptor
      mediated and receptor-independent actions in cells of the oral cavity. Melatonin
      is released into the saliva by the acinar cells of the major salivary glands and
      via the gingival fluid. Functions of melatonin in the oral cavity are likely to
      relate primarily to its anti-inflammatory and antioxidant activities. These
      actions may suppress inflammation of the gingiva and periodontium, reduce
      alveolar bone loss, abrogate herpes lesions, enhance osteointegration of dental
      implants, limit oral cancer, and suppress disorders that have a free radical
      component. Sublingual melatonin tablets or oral melatonin sprays and topical
      melatonin-containing gel, if used on a regular basis, may improve overall oral
      health and reduce mucosal lesions. CONCLUSION: Collectively, the results indicate
      that endogenously-produced and exogenously-applied melatonin are beneficial to
      the oral cavity.

PMID- 24665832
TI  - Laparoendoscopic single-site versus conventional laparoscopic pyeloplasty: a
      matched pair analysis.
AB  - OBJECTIVE: To compare the outcomes of laparoendoscopic single-site pyeloplasty
      versus those of conventional laparoscopic pyeloplasty. METHODS: A total of 26
      laparoendoscopic single-site pyeloplasty cases carried out in University
      Hospital: Kyoto Prefectural University of Medicine, Kyoto, Japan, from 2008 to
      2013 were compared with a control group of 26 age-matched laparoscopic
      pyeloplasty cases carried out during the same study period. RESULTS: The mean age
      of the patients was 20.4 years (range 1-56 years). Laparoendoscopic single-site
      pyeloplasty was carried out on the right in nine cases and on the left in 17
      cases. The operative time was 246 +/- 68 min. Regarding the 14 pediatric
      patients, the mean age was 7.1 years (range 1-14 years). The operative time was
      243 +/- 49 min. As for the 12 adult patients, the mean age was 35.8 years (range
      16-56 years). The operative time was 248 +/- 86 min. The mean operative time of
      the control group in age-matched laparoscopic pyeloplasty was 239 +/- 51 min.
      Times were 229 +/- 54 min for the pediatric patients and 253 +/- 45 min for the
      adult patients. There was no significant difference in the operative time between
      the control group and the laparoendoscopic single-site group for both adults and
      children. Blood loss was minimal, and no intraoperative and postoperative
      complications were observed in the 26 laparoendoscopic single-site pyeloplasty
      cases. CONCLUSION: The present findings suggest that laparoendoscopic single-site
      pyeloplasty can be used in both pediatric and adult patients, offering a superior
      cosmetic outcome than conventional laparoscopic pyeloplasty, and a lower degree
      of postoperative pain. A large-scale prospective, randomized study is required to
      confirm these findings, and to define the future role of laparoendoscopic single
      site pyeloplasty.

PMID- 24665833
TI  - Osteoclast-like cells on deproteinized bovine bone mineral and biphasic calcium
      phosphate: light and transmission electron microscopical observations.
AB  - OBJECTIVES: The occurrence of multinucleated giant cells (MNGCs) on bone
      substitute materials has been recognized for a long time. However, there have
      been no studies linking material characteristics with morphology of the MNGCs.
      The aim was to analyze the qualitative differences of MNGCs on two commercially
      available calcium phosphate bone substitute materials retrieved from bone
      defects. MATERIAL AND METHODS: Six defects were prepared bilaterally in the
      mandibular body of three mini pigs. The defects were randomly grafted with either
      deproteinized bovine bone mineral (DBBM) or biphasic calcium phosphate (BCP).
      After a healing period of four weeks, bone blocks were embedded in LR White
      resin. Three consecutive sections per defect were analyzed as follows: two with
      light microscopy using toluidine blue and tartrate-resistant acid phosphatase
      (TRAP) staining and one with transmission electron microscopy. RESULTS:
      Multinucleated giant cells appeared on both biomaterials. On BCP, MNGCs had a
      flat morphology and were not observed in resorption lacunae. On DBBM, the MNGCs
      appeared more round and were often found in shallow concavities. MNGCs on both
      biomaterials demonstrated a varying degree of TRAP staining, with a tendency
      toward higher staining intensity of MNGCs on BCP. At the ultrastructural level,
      signs of superficial dissolution of BCP together with phagocytosis of minor
      fragments were observed. MNGCs on the surface of DBBM demonstrated sealing zones
      and ruffled borders, both features of mature osteoclasts. CONCLUSION: MNGCs
      demonstrated distinctly different histological features depending on the bone
      substitute material used. Further research is warranted to understand the
      clinical implications of these morphological observations.

PMID- 24665834
TI  - New flavonoids from the stem bark of Erythrina caffra Thunb.
AB  - Three new flavonoids 5,7-dihydroxy-2',4'-dimethoxy-5'-formylisoflavanone
      (erycaffra E) (1), 5,7-dihydroxy-3'-(2"-hydroxy-3"-methylbut-3-enyl)-5'-(3'''
      hydroxy-3'''-methyl-trans-but-1-enyl)-4'-methoxyflavanone (erycaffra D) (2) and
      5,7-dihydroxy-4'-methoxy-3',5'-di-(3"-hydroxy-3"-methyl-trans-but-1
      enyl)flavanone (erycaffra F) (3) were isolated from the stem bark of Erythrina
      caffra along with four known compounds, namely 5,4'-dihydroxy-6-(3"-methylbut-2"
      enyl)-5'''-hydroxyisopropyldihydrofurano[2''',3''':7,8]isoflavone
      (isosenegalensein) (4), 5,7-dihydroxy-4'-methoxy-3'-(3"-methylbut-2-enyl)-5'
      (3'''-hydroxy-3'''-methylbut-1-enyl)flavanone (burttinone) (5), 5,4'-dihydroxy-5"
      hydroxyisopropyldihydrofurano[2''',3''':7,6]isoflavone (erythrinin C) (6) and
      5,4'-dihydroxy-6"-hydroxymethyl-6"-methylpyrano[2",3":6,7]isoflavone (erysubin B)
      (7). The structures were determined on the basis of spectroscopic data (1D, 2D
      NMR and MS) and by comparison with literature values. 

PMID- 24665835
TI  - MicroRNA-mediated regulation of melanoma.
AB  - Melanoma is one of the most aggressive and deadly skin cancers, and, in its
      advanced stages, accounts for > 80% mortality. The incidence of melanoma is
      increasing worldwide; however, beyond surgical removal of the tumour, there is
      currently no curative therapy available, especially for its advanced stages. This
      may, in part, be owing to incomplete understanding of the molecular mechanisms
      that regulate the initiation and/or progression of melanoma to metastasis. The
      molecular mechanisms leading to the development and progression of melanoma are
      the focus of intense investigation, and many genetic/epigenetic alterations
      affecting melanoma progression and development have been identified. microRNAs
      (miRNAs) are emerging as important causal modulators in the development and
      progression of melanoma. The understanding of miRNA-mediated regulation of
      tumours has grown immensely over the last few years, as it has been understood to
      regulate most biological processes. Here, we review the currently available data
      on miRNAs associated with melanoma, highlighting those deregulated miRNAs that
      target important genes and pathways involved in the progression of melanocytes to
      primary and metastatic melanoma. We also review their potential clinical utility
      as biomarkers and potential use in targeted therapy. 

PMID- 24665836
TI  - Severe auditory processing disorder secondary to viral meningoencephalitis.
AB  - OBJECTIVE: To describe auditory function in an individual with bilateral damage
      to the temporal and parietal cortex. DESIGN: Case report. STUDY SAMPLE: A
      previously healthy 17-year old male is described who sustained extensive cortical
      injury following an episode of viral meningoencephalitis. He developed status
      epilepticus and required intubation and multiple anticonvulsants. RESULTS: Serial
      brain MRIs showed bilateral temporoparietal signal changes reflecting extensive
      damage to language areas and the first transverse gyrus of Heschl on both sides.
      The patient was referred for assessment of auditory processing but was so
      severely impaired in speech processing that he was unable to complete any formal
      tests of his speech processing abilities. Audiological assessment utilizing
      objective measures of auditory function established the presence of normal
      peripheral auditory function and illustrates the importance of the use of
      objective measures of auditory function in patients with injuries to the auditory
      cortex. CONCLUSIONS: Use of objective measures of auditory function is essential
      in establishing the presence of normal peripheral auditory function in
      individuals with cortical damage who may not be able to cooperate sufficiently
      for assessment utilizing behavioral measures of auditory function.

PMID- 24665837
TI  - Chondrogenic differentiation of marrow clots after microfracture with BMSC
      derived ECM scaffold in vitro.
AB  - Repairing articular cartilage by combining microfracture and various scaffolds
      has been extensively performed in in vivo animal models. We previously described
      a novel extracellular matrix (ECM) scaffold for cartilage tissue engineering. The
      aim of this study was to investigate the effect of a bone marrow-derived
      mesenchymal stem cells-derived ECM (BMSC-dECM) scaffold on the chondrogenic
      differentiation of marrow clots following microfracture in vitro. In this study,
      we manufactured the BMSC-dECM scaffold using a freeze-drying method. To obtain
      the marrow clots, a full-thickness cartilage defect was established and
      microholes were created in the trochlear groove of New Zealand white rabbits. The
      samples were divided and cultured in vitro for 1, 2, 4, and 8 weeks. The samples
      included a culture of the marrow clot alone (Group 1), a culture of the marrow
      clot with transforming growth factor-beta 3 (TGF-beta3) (Group 2), a culture of
      the composite of the BMSC-dECM scaffold and the marrow clot alone (Group 3), and
      a culture of the composite with TGF-beta3 (Group 4). A smooth and glossy surface
      was observed in Group 2 and Group 4 over time, but the surface for Group 4 was
      larger from week 1 onward. Compressive strength gradually increased in Groups 2
      and 4, and greater increases were observed in Group 4 during the 8-week culture
      period. Enhanced cartilage-like matrix deposition of glycosaminoglycan (GAG) and
      type II collagen were confirmed by Safranin O and immunohistochemistry staining,
      respectively, in Groups 2 and 4. The GAG and collagen contents also gradually
      increased over time in Groups 2 and 4; the increase was greater in Group 4. In
      addition, real-time-polymerase chain reaction demonstrated that the expression of
      chondrogenic genes, such as COL2, ACAN, and SOX9, was gradually upregulated in
      Groups 2 and 4. However, greater increases in the expression of these cartilage
      like genes were observed in Group 4 from week 4 onward. Our results suggest that
      the BMSC-dECM scaffold may favor the chondrogenesis of marrow clots following
      microfracture in vitro. In conclusion, these tissue engineering-like constructs
      could be potential candidates for cartilage repair. 

PMID- 24665838
TI  - Preface: In 2013 gene therapy is a Nike; for 2014, just do it!

PMID- 24665839
TI  - Targeted genome editing tools for disease modeling and gene therapy.
AB  - The development of custom-designed nucleases (CDNs), including zinc finger
      nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs),
      has made it possible to perform precise genetic engineering in many cell types
      and species. More recently, clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated (Cas) system has been successfully employed
      for genome editing. These RNA-guided DNA endonucleases are shown to be more
      efficient and flexible than CDNs and hold great potential for applications in
      both biological studies and medicine. Here, we review the progress that has been
      made for all three genome editing technologies in modifying both cells and model
      organisms, compare important aspects of each approach, and summarize the
      applications of these tools in disease modeling and gene therapy. In the end, we
      discuss future prospects of the field. 

PMID- 24665840
TI  - Recent advances and future trends in the targeted therapy of metastatic gastric
      cancer.
AB  - The better understanding of the molecular mechanisms behind gastric cancer has
      led to the development of new therapeutic strategies that are likely to improve
      patient outcomes in the near future. Recently, targeting the HER2 and the VEGF
      pathways with trastuzumab and ramucirumab, respectively, have been found to
      improve survival, while directed therapies against a number of other pathways are
      under clinical evaluation. These include the hepatocyte growth factor and its
      receptor c-MET, the insulin-like growth factor 1, the fibroblast growth factor,
      the mammalian target of rapamycin (mTOR), the epidermal growth factor receptor,
      and other pathways, as well as relevant immunotherapeutic strategies. This
      article reviews recent advances and future trends of these concepts for gastric
      cancer and adenocarcinoma of the gastroesophageal junction. 

PMID- 24665842
TI  - Expression of Fas (CD95/APO-1) and Fas ligand (FasL) in experimentally-induced
      acute pancreatitis.
AB  - INTRODUCTION: Acinar cell death is a crucial event in acute pancreatitis (AP) and
      may occur either by apoptosis or necrosis. The aim of this study was to
      investigate the expression of the apoptosis associated proteins Fas and FasL in
      experimentally induced severe AP. METHODS: AP was induced in 30 rats by injecting
      0.2 ml of 4.5% sodium taurocholate solution into the biliopancreatic duct. Sham
      operated animals (n = 30) and 10 normal controls were used for comparisons.
      Animals were killed at 6, 12, 24, 48, 72 hr and 1 week after operation (five
      animals at each time point) and both serum and pancreatic tissue were obtained.
      The severity of AP was graded by morphological evaluation and by measuring serum
      amylase levels. Acinar cell apoptosis was detected by the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling
      (TUNEL) assay. Tissue expressions of Fas and FasL were evaluated by
      immunohistochemistry. RESULTS: Sodium taurocholate injection resulted in severe
      acute necrotizing pancreatitis as early as six hr after taurocholate infusion
      with gradually increasing severity and a peak at 72 hr, and a significant
      increase of serum amylase at 6 and 12 hr. Apoptotic acinar cells were observed
      between 48 and 72 hr. The expression of both Fas and FasL in pancreatic tissue
      was induced in comparison with normal controls. Fas expression in AP was higher
      and statistically significant at 24 hr whereas FasL expression was consistently
      lower with a statistical significance observed at 12 hr when compared to sham
      operated animals suggesting Fas upregulation and FasL downregulation in this
      model of AP. CONCLUSIONS: Induction and sequential changes in the expressions of
      Fas and FasL occur during taurocholate induced severe AP in rats and their
      temporal modulation might associate with acinar cell death by apoptosis.

PMID- 24665843
TI  - Influence of laparoscopy vs. laparotomy on bacterial translocation and systemic
      inflammatory responses in a porcine model with peritonitis.
AB  - BACKGROUND: This study aimed to compare the effects of laparoscopy vs. laparotomy
      on bacterial translocation and immunologic responses in a porcine model with
      peritonitis caused by small bowel injuries (SBIs). METHODS: Pigs with SBIs were
      first established, assigned into either the laparoscopy group or the laparotomy
      group, and then received surgical intervention. During 72 hours (72 hr)
      observation period, blood, and tissues of different organs were obtained for
      bacterial cultures; endotoxin and peripheral leukocyte were determined; serum
      levels of IL-6, TNF-alpha, and CRP were measured. RESULTS: Blood cultures
      confirmed systemic bacteremia in all animals and the endotoxin level was
      comparable between groups at 24 hr after surgery. However, two days later,
      positive bacteremia was only detected in four pigs following laparoscopy and five
      following laparotomy. Eight and four pigs during laparoscopy (seven and six pigs
      during laparotomy) had translocated bacteria in mesenteric lymph nodes (MLN) and
      liver. The 72 hr later, bacteria in MLN, liver, lung, and kidney was found in 2,
      1, 2, and 0 pig after laparoscopy, respectively (3, 2, 2, and 1 pig after
      laparotomy). The peripheral blood monocytes (PBMC) counts remained at a much
      lower level after laparoscopy than after laparotomy. Serum IL-6, TNF-alpha, and
      CRP increased notably after both procedures when compared to preoperative levels.
      However, significantly faster and lower regression of IL-6, TNF-alpha, and CRP
      were observed in the laparoscopy group. CONCLUSION: Compared with laparotomy,
      laparoscopy does not result in increased bacterial translocation, but decrease IL
      6, TNF-alpha, and CRP release.

PMID- 24665841
TI  - Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse
      collagen-induced arthritis model.
AB  - Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid
      arthritis (RA). To support ongoing clinical development of an anti-C5aR
      monoclonal antibody, we have investigated for the first time the mechanism of
      action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR)
      surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was
      demonstrated in a multiple-dose treatment study. Almost complete inhibition of
      clinical disease progression was obtained, including reduced bone and cartilage
      destruction in anti-mC5aR-treated mice. Then, the mechanism of action was
      examined by looking for early effects of anti-mC5aR treatment in single-dose
      treatment studies. We found that 48 h after single-dose treatment with anti
      mC5aR, the neutrophil and macrophage infiltration into the paws was already
      reduced. In addition, several inflammatory markers, including tumour necrosis
      factor (TNF)-alpha, interleukin (IL)-6 and IL-17A were reduced locally in the
      paws, indicating reduction of local inflammation. Furthermore, dose-setting
      experiments supported a beneficial clinical effect of dosing above the C5aR
      saturation level. In conclusion, these preclinical data demonstrated rapid onset
      effects of antibody blockade of C5aR. The data have translational value in
      supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in
      rheumatoid arthritis patients, by identifying potential biomarkers of treatment
      effects as well as by providing information on pharmacodynamics and novel
      insights into the mechanism of action of monoclonal antibody blockade of C5aR. 

PMID- 24665844
TI  - The effect of intraoperative fluid volume administration on pancreatic fistulas
      after pancreaticoduodenectomy.
AB  - BACKGROUND: Fluid therapy may be one of the most controversial topics in
      perioperative management. However, data concerning the influence of perioperative
      fluid administration on complications after pancreaticoduodenectomy are sparse.
      METHODS: A group of 147 patients underwent pancreaticoduodenectomy for benign or
      malignant pathology of the pancreas or the periampullary region between 2005 and
      2009. Clinical data, overall morbidity, and long-term outcomes were recorded.
      RESULTS: We categorized the patients into two groups according to intraoperative
      fluid volume administration: a low fluid volume group (LFVG, <8.2 ml kg(-1) hr(
      1), n = 90) group, and a high fluid volume group (HFVG, >=8.2 ml kg(-1) hr(-1), n
      = 57). In terms of colloid administration, the high fluid volume group received
      significantly more colloid both during the intraoperative period and 0-12 hr
      after surgery (p < .001 and p < .007, respectively). Pancreatic fistula rates
      were significantly greater in the high fluid volume group (p = .035). However,
      the long-term survival rate was not different between the two groups.
      CONCLUSIONS: High intraoperative fluid volume administration is associated with
      an increased incidence of pancreatic fistulas after pancreaticoduodenectomy.

PMID- 24665848
TI  - TOC for proceedings.

PMID- 24665847
TI  - Editorial.

PMID- 24665846
TI  - Hematopoietic repopulating ability of CD34+ progenitor cells ex vivo expanded
      with different cytokine combinations.
AB  - Ex-vivo expansion technologies were developed for application of hematopoietic
      stem cells (HSCs) derived from cord blood (CB). The cytokine combination was
      essential to expand HSCs ex vivo and maintain the function of expanded HSCs.
      However the optimal cytokine combination was not determined. In this study, two
      combinations of cytokines were applied in ex-vivo expansion of HSCs to
      investigate the effect on the hematopoietic repopulating ability of expanded
      HSCs. CB CD34(+) cells were expanded with SCF + TPO + FL (STF) or SCF + TPO + FL
      + IL-3 + IL-6 (STF36) for 7 days and got 30.3 +/- 6.4 and 39.8 +/- 7.3 folds of
      total cells, respectively. The cells cultured by both STF and STF36 could engraft
      and repopulate in non-obese diabetic/severe combined immunodeficiency (NOD/SCID)
      mice effectively; however, the STF group achieved higher level of engraftment.
      These result demonstrated that the cytokine combination of STF36 favored the
      expansion of cells, while the cytokine combination of STF facilitated the
      engraftment and multi-lineage repopulating in vivo. These findings may have
      important implications for the cell therapy. 

PMID- 24665850
TI  - Call for papers 2015 ACC RAC.

PMID- 24665849
TI  - Peer review acknowledgments.

PMID- 24665851
TI  - Call for workshop proposals 2015 ACC RAC.

PMID- 24665852
TI  - Establishing a transoral robotic surgery program in an academic hospital in
      Germany.
AB  - The application of robot technology in the field of surgery has grown rapidly in
      recent years. Also in Europe, robot-assisted surgery has become increasingly
      popular, predominantly in the fields of urology and gynecology. Transoral robotic
      surgery (TORS) is widely practiced in North America after receiving FDA approval
      in 2009. This technique was also adopted and is being practiced at specialized
      institutions in various European countries, including Germany. Due to significant
      differences in the health-care system and divergent developments of the use of
      transoral surgery in the treatment of laryngeal and pharyngeal malignancies in
      the last decade between North America and Europe, there are unique barriers and
      challenges to introducing TORS in these two parts of the world. This article
      describes experiences in developing a TORS program at an academic hospital in
      Germany. Specifically, steps that were required to obtain institutional approval
      and financial support, as well as to train surgeons and allied health-care
      personnel, and to establish a sufficient and adequate technique for reprocessing
      the used instruments are presented. Introducing a TORS program in Europe is still
      a challenge in regard to financial issues, acceptance, and practicability and
      therefore it is only practiced in specialized centers, although systems are
      widely available and often used in the same hospital by urology departments.

PMID- 24665854
TI  - Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.
AB  - Neurological complications after renal transplantation constitute an important
      cause of morbidity and mortality. Their differential diagnosis is difficult and
      essential for subsequent patient's management. Valproate-induced hyperammonemic
      encephalopathy is an uncommon but serious effect of valproate treatment. Here, we
      describe the case of a 15-year-old girl who was on a long-term therapy with
      valproate due to epilepsy and revealed impaired consciousness with hyperammonemia
      12 days after renal transplantation. After withdraw of valproate, patients'
      symptoms resolved within 24 h. Clinicians should increase their awareness for
      potential complication of valproate, especially in transplanted patients.

PMID- 24665853
TI  - Surgical management of facial paralysis resulting from temporal bone fractures.
AB  - CONCLUSION: To achieve good facial reanimation in cases with facial paralysis
      resulting from temporal bone fractures, the ideal timing for surgical
      intervention is at least within 1 month of injury and an appropriate surgical
      approach should be selected depending on the site of facial nerve injury.
      OBJECTIVE: This paper aimed to address the ideal time for surgical intervention
      and the appropriate surgical approach for patients with facial paralysis
      resulting from temporal bone fractures. METHODS: We retrospectively investigated
      60 patients with facial paralysis due to temporal bone fractures who underwent
      facial nerve decompression via different operative approaches within 1 month
      after trauma, of which 48 were surgically treated by the middle cranial fossa
      approach (80%), 8 by a pure transmastoid approach (13.3%), and four by a combined
      transmastoid and middle cranial fossa approach (6.7%). The House-Brackmann (H-B)
      grading system was used to evaluate the recovery of facial nerve function.
      RESULTS: The follow-up period for all the patients was 1 year. Among 60 patients
      who were surgically treated, 39 achieved grade I of facial nerve function, 18
      achieved grade II, two achieved grade III, and one achieved grade IV according to
      the H-B grading system.

PMID- 24665855
TI  - Awareness of the role of science in the FDA regulatory submission process: a
      survey of the TERMIS-Americas membership.
AB  - The Industry Committee of the Tissue Engineering Regenerative Medicine
      International Society, Americas Chapter (TERMIS-AM) administered a survey to its
      membership in 2013 to assess the awareness of science requirements in the U.S.
      Food and Drug Administration (FDA) regulatory process. One hundred forty-four
      members responded to the survey. Their occupational and geographical
      representation was representative of the TERMIS-AM membership as a whole. The
      survey elicited basic demographic information, the degree to which members were
      involved in tissue engineering technology development, and their plans for future
      involvement in such development. The survey then assessed the awareness of
      general FDA scientific practices as well as specific science requirements for
      regulatory submissions to the Center for Biologics Evaluation and Research
      (CBER), the Center for Drug Evaluation and Research (CDER), the Center for
      Devices and Radiological Health (CDRH), and the Office of Combination Projects
      (OCP). The FDA-specific questions in the survey were culled from guidance
      documents posted on the FDA web site ( www.fda.gov ). One of the answer options
      was an opt-out clause that enabled survey respondents to claim a lack of
      sufficient awareness of the topic to answer the question. This enabled the
      stratification of respondents on the basis of confidence in the topic. Results
      indicate that across all occupational groups (academic, business, and government)
      that are represented in the TERMIS-AM membership, the awareness of FDA science
      requirements varies markedly. Those who performed best were for-profit company
      employees, consultants, and government employees; while students, professors, and
      respondents from outside the USA performed least well. Confidence in question
      topics was associated with increased correctness in responses across all groups,
      though the association between confidence and the ability to answer correctly was
      poorest among students and professors. Though 80% of respondents claimed
      involvement in the development of a tissue engineering technology, their
      responses were no more correct than those who were not. Among those developing
      tissue engineering technologies, few are taking advantage of existing standards
      organizations to strengthen their regulatory submissions. The data suggest that
      early exposure to regulatory experts would be of value for those seeking to bring
      their technology to the market. For all groups studied but especially for
      students and professors, formal initial or continuing education in Regulatory
      Science should be considered to best support translational tissue engineering
      research and development. In addition, the involvement of standards development
      organizations during tissue engineering technology development is strongly
      recommended. 

PMID- 24665856
TI  - The epigenetically regulated effects of Wnt antagonists on the expression of
      genes in the apoptosis pathway in human bladder cancer cell line (T24).
AB  - The epigenetic suppression of Wnt antagonists (sFRPs, DKKs, and WIF-1) causes the
      activation of both beta-catenin and target genes, which play an important role in
      cell proliferation, metastasis, and angiogenesis. This study is aimed to
      investigate, on transcriptional and protein levels, the synergic effects of
      unaccompanied and/or combined use of 5-aza-2'-deoxycytidine (DAC, 5-aza-dC),
      trichostatin A (TSA), and gemcitabine+cisplatin chemotherapeutic agents on the
      apoptotic pathway of human bladder cancer cell line T24. The anti-tumor effects
      of gemcitabine (0-500 nM), cisplatin (0-10 MUM), DAC (10 MUM), and TSA (300 nM)
      alone and/or together on T24 cells were determined by WST-1. ELISA method was
      used to analyze the effects of unaccompanied and combined use of
      gemcitabine+cisplatin, DAC, and TSA on cell proliferation and determine the
      cytotoxic and apoptotic dosages at the level of H3 histone acetylation.
      Methylation-specific PCR was used to evaluate methylation profiles of Wnt
      antagonist gene (WIF-1). In the case of unaccompanied and/or combined use of
      specified drugs, the variations in the expression levels of CTNNB1, GSK3beta, c
      MYC, CCND1, CASP-3, CASP-8, CASP-9, BCL2L1, and WIF-1 genes were determined by
      quantitative real-time PCR. Our results indicate that through inhibition of DNA
      methylation, expression of beta-catenin and Wnt antagonist re-activation and
      expressions of canonical Wnt/beta-catenin pathway target genes, c-myc and cyclin
      D1 (CCND1), have decreased. In addition, DAC, TSA, and gemcitabine+cisplatin
      combination caused an increase in GSK3beta mRNA levels, which in turn
      significantly decreased CCND1 mRNA levels. Moreover, BCL2L1, an anti-apoptotic
      gene, was downregulated significantly. Meanwhile, both CASP-3 mRNA and active
      caspase-3 protein levels increased with respect to control (p<0.01). The results
      revealed that use of quadruplicate gemcitabine+cisplatin+DAC+TSA combination led
      to a reduced inhibition of canonical Wnt/beta-catenin pathway and reduced cell
      proliferation. Our findings may offer a new approach to consider in the treatment
      of bladder cancer.

PMID- 24665857
TI  - Ratiometric fluorescent probe for rapid detection of bisulfite through 1,4
      addition reaction in aqueous solution.
AB  - A ratiometric fluorescent probe based on a positively charged benzo[e]indolium
      moiety for bisulfite is reported. The bisulfite underwent a 1,4-addition reaction
      with the C-4 atom in the ethylene group. This reaction resulted in a large
      emission wavelength shift (Deltalambda = 106 nm) and an observable fluorescent
      color change from orange to cyan. The reaction could be completed in 90 s in a
      PBS buffer solution and displayed high selectivity and sensitivity for bisulfite.
      A simple paper test strip system was developed to detect bisulfite rapidly. Probe
      1 was used to detect bisulfite in real samples with good recovery. 

PMID- 24665858
TI  - Proteomics in farm animals: quo vadis?

PMID- 24665859
TI  - Bispidine analogues of cisplatin, carboplatin, and oxaliplatin. synthesis,
      structures, and cytotoxicity.
AB  - Bispidine (3,7-diazabicyclo[3.3.1]nonane, C7H14N2) analogues of cisplatin,
      carboplatin, and oxaliplatin have been prepared. (C7H14N2)PtCl2.DMF (1b),
      obtained from (1,5-hexadiene)PtCl2 and bispidine in DMF, is dimeric in the solid
      state. Dissolving 1b in hot N-methylformamide allows crystallization of the
      solvent-free polymeric (C7H14N2)PtCl2 (1a). Recrystallization of 1a,b from hot
      water yields the trihydrate (C7H14N2)PtCl2.3H2O (1c). Reaction of 1 with
      Ag2(cbdca) (cbdca = 1,1-cyclobutanedicarboxylate) in water affords the
      pentahydrate (C7H14N2)Pt{C4H6(CO2)2}.5H2O (2b), which loses water in vacuo to
      give (C7H14N2)Pt{C4H6(CO2)2} (2a). Reaction of 1 with AgNO3 in water, followed by
      addition of Na2C2O4, affords the water-free polymeric (C7H14N2)Pt(C2O4) (3). All
      complexes have been structurally characterized, revealing various patterns of N
      H...Cl and N-H...O hydrogen bonds. In the hydrates 1c and 2b the complexes are
      embedded in intricate three-dimensional water networks. Complexes 1a, 2a, and 3
      have been tested for their cytotoxicity against human cancer cell lines K562
      (chronic myeloid leukemia), A2780 (ovarian cancer), and its platinum-resistant
      subline A2780 CisR and are compared to their parent analogues. The new complexes
      show significant cytotoxic activity along with a low platinum resistance factor. 

PMID- 24665860
TI  - Dumbbell-type fullerene-steroid hybrids: a join experimental and theoretical
      investigation for conformational, configurational, and circular dichroism
      assignments.
AB  - New [60]fullerene-steroid conjugates (4-6) have been synthesized by 1,3-dipolar
      cycloaddition and Bingel-Hirsch cyclopropanation reactions from suitably
      functionalized epiandrosterone and [60]fullerene. Since a new stereocenter is
      created in the formation of the Prato monoaduct, two different diastereomers were
      isolated by HPLC (4, 5) whose absolute configurations were assigned according to
      the highly reliable "sector rule" on fullerenes. A further reaction of the
      malonate-containing diastereomer 5 with a second C60 molecule has afforded
      dumbbell fullerene 6 in which the two fullerene units are covalently connected
      through an epiandrosterone moiety. The new compounds have been spectroscopically
      characterized and their redox potentials, determined by cyclic voltametry, reveal
      three reversible reduction waves for hybrids 4 and 5, whereas these signals are
      split in dumbbell 6. Theoretical calculations at semiempirical (AM1) and single
      point B3LYP/6-31G(d) levels have predicted the most stable conformations for the
      hybrid compounds (4-6), showing the importance of the chlorine atom on the D ring
      of the steroid. Furthermore, TDDFT calculations have allowed assignments of the
      experimentally determined circular dichroism (CD) of the [60]fullerene-steroid
      hybrids based on the sign and position of the Cotton effects, despite the
      exceptionally large systems under study.

PMID- 24665861
TI  - Synthesis of pH-responsive chitosan nanocapsules for the controlled delivery of
      doxorubicin.
AB  - Well-defined chitosan nanocapsules (CSNCs) with tunable sizes were synthesized
      through the interfacial cross-linking of N-maleoyl-functionalized chitosan (MCS)
      in miniemulsions, and their application in the delivery of doxorubicin (Dox) was
      investigated. MCS was prepared by the amidation reaction of CS with maleic
      anhydride in water/DMSO at 65  degrees C for 20 h. Subsequently, thiol-ene cross
      linking was conducted in oil-in-water miniemulsions at room temperature under UV
      irradiation for 1 h, using MCS as both a surfactant and precursor polymer, 1,4
      butanediol bis(3-mercapto-propionate) as a cross-linker, and D-alpha-tocopheryl
      poly(ethylene glycol) 1000 succinate as a cosurfactant. With the increase in
      cosurfactant concentration in the reaction systems, the sizes of the resulting
      CSNCs decreased steadily. Dox-loaded CSNCs were readily prepared by in situ
      encapsulation of Dox during miniemulsion cross-linking. With acid-labile beta
      thiopropionate cross-linkages, the Dox-loaded CSNCs demonstrated a faster release
      rate under acidic conditions. Relative to free Dox, Dox-loaded CSNCs exhibited
      enhanced cytotoxicity toward MCF-7 breast cancer cells without any noticeable
      cytotoxicity from empty CSNCs. The effective delivery of Dox to MCF-7 breast
      cancer cells via Dox-loaded CSNCs was also observed.

PMID- 24665862
TI  - Management of fatty liver disease with the metabolic syndrome.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the liver disease of this century,
      increasing in parallel with obesity, insulin resistance and the metabolic
      syndrome. NAFLD can be seen as a component of the metabolic syndrome, and as
      such, contributing as a risk factor for cardiovascular disease. In fact, these
      patients die more often from cardiovascular disease than from direct consequences
      of liver disease. In this review, we will summarize the data that link NAFLD as a
      central player in this dysmetabolism, as well as the evidence for appropriate
      therapy, in order to improve not only liver disease prognosis, but also the
      overall prognosis and risk of mortality, with particular focus on cardiovascular
      risk. 

PMID- 24665863
TI  - Detergent optimized membrane protein reconstitution in liposomes for solid state
      NMR.
AB  - For small helical membrane proteins, their structures are highly sensitive to
      their environment, and solid state NMR is a structural technique that can
      characterize these membrane proteins in native-like lipid bilayers and
      proteoliposomes. To date, a systematic method by which to evaluate the effect of
      the solubilizing detergent on proteoliposome preparations for solid state NMR of
      membrane proteins has not been presented in the literature. A set of experiments
      are presented aimed at determining the conditions most amenable to dialysis
      mediated reconstitution sample preparation. A membrane protein from M.
      tuberculosis is used to illustrate the method. The results show that a detergent
      that stabilizes the most protein is not always ideal and sometimes cannot be
      removed by dialysis. By focusing on the lipid and protein binding properties of
      the detergent, proteoliposome preparations can be readily produced, which provide
      double the signal-to-noise ratios for both the oriented sample and magic angle
      spinning solid state NMR. The method will allow more membrane protein drug
      targets to be structurally characterized in lipid bilayer environments. 

PMID- 24665864
TI  - Surface functionalization and electronic interactions of ZnO nanorods with a
      porphyrin derivative.
AB  - To optimize electron transfer and optoelectronic properties in nanoparticulate
      thin films for electronics we show the surface functionalization of ZnO nanorods
      by means of replacing surface active 2-[2-(2-methoxyethoxy)ethoxy]acetic acid
      (TODA) by a redoxactive organic component, that is, 5,10,15,20-(phenoxyacetat)
      porphyrin bearing four carboxylic acids as possible ZnO anchors. Microscopy
      transmission electron microscopy-and spectroscopy-optical spectroscopy-verifies
      the successful and homogenous integration of the porphyrin onto the surface of
      ZnO nanorods, a process that is facilitated by the four anchoring groups.
      Photophysical investigations based on emission and absorption spectroscopy prompt
      to distinct electronic interactions between ZnO nanorods and the porphyrins.
      Consequently, we performed further photophysical studies flanked by pulse
      radiolysis assays to corroborate the nature of the electronic interactions. 

PMID- 24665865
TI  - Visual assessment of the cervical vertebral maturation stages: A study of
      diagnostic accuracy and repeatability.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy and repeatability of the visual
      assessment of the cervical vertebral maturation (CVM) stages. MATERIALS AND
      METHODS: Ten operators underwent training sessions in visual assessment of CVM
      staging. Subsequently, they were asked to stage 72 cases equally divided into the
      six stages. Such assessment was repeated twice in two sessions (T1 and T2) 4
      weeks apart. A reference standard for each case was created according to a
      cephalometric analysis of both the concavities and shapes of the cervical
      vertebrae. RESULTS: The overall agreement with the reference standard was about
      68% for both sessions and 76.9% for intrarater repeatability. The overall kappa
      coefficients with the reference standard were up to 0.86 for both sessions, and
      0.88 for intrarater repeatability. Overall, disagreements one stage and twp stage
      apart were 23.5% (T1) and 5.1% (T2), respectively. Sensitivity ranged from 53.3%
      for CS5 (T1) to 99.9% for CS1 (T2), positive predictive values ranged from 52.4%
      for CS5 (T2) to 94.3% for CS6 (T1), and accuracy ranged from 83.6% for CS4 (T2)
      to 94.9% for CS1 (T1). CONCLUSIONS: Visual assessment of the CVM stages is
      accurate and repeatable to a satisfactory level. About one in three cases remain
      misclassified; disagreement is generally limited to one stage and is mostly seen
      in stages 4 and 5.

PMID- 24665866
TI  - Early-stage development of novel cyclodextrin-siRNA nanocomplexes allows for
      successful postnebulization transfection of bronchial epithelial cells.
AB  - BACKGROUND: Successful delivery of small interfering RNA (siRNA) to the lungs
      remains hampered by poor intracellular delivery, vector-mediated cytotoxicity,
      and an inability to withstand nebulization. Recently, a novel cyclodextrin (CD),
      SC12CDClickpropylamine, consisting of distinct lipophilic and cationic subunits,
      has been shown to transfect a number of cell types. However, the suitability of
      this vector for pulmonary siRNA delivery has not been assessed to date. To
      address this, a series of high-content analysis (HCA) and postnebulization assays
      were devised to determine the potential for CD-siRNA delivery to the lungs.
      METHODS: SC12CDClickpropylamine-siRNA mass ratios (MRs) were examined for size
      and zeta potential. In-depth analysis of nanocomplex uptake and toxicity in Calu
      3 bronchial epithelial cells was examined using IN Cell((r)) HCA assays.
      Nebulized SC12CDClickpropylamine nanocomplexes were assessed for volumetric
      median diameter (VMD) and fine particle fraction (FPF) and compared with saline
      controls. Finally, postnebulization stability was determined by comparing
      luciferase knockdown elicited by SC12CDClickpropylamine nanocomplexes before and
      after nebulization. RESULTS: SC12CDClickpropylamine-siRNA complexation formed
      cationic nanocomplexes of <=200 nm in size depending on the medium and led to
      significantly higher levels of siRNA associated with Calu-3 cells compared with
      RNAiFect-siRNA-treated cells at all MRs (p<0.001, n=3*4), with evidence of
      toxicity only at MRs 50-100. Nebulization of SC12CDClickpropylamine nanocomplexes
      using the Aeroneb((r)) Pro resulted in VMDs of ~4 MUm and FPFs of ~57% at all
      MRs. SC12CDClickpropylamine-siRNA-mediated luciferase knockdown was found to be
      39.8+/-3.6% at MR=20 before and 35.6+/-4.55% after nebulization, comparable to
      results observed using unnebulized commercial transfection reagent, RNAiFect.
      CONCLUSIONS: SC12CDClickpropylamine nanocomplexes can be effectively nebulized
      for pulmonary delivery of siRNA using Aeroneb technology to mediate knockdown in
      airway cells. To the best of our knowledge, this is the first study examining the
      suitability of SC12CDClickpropylamine-siRNA nanocomplexes for pulmonary delivery.
      Furthermore, this work provides an integrated nanomedicine-device combination for
      future in vitro and in vivo preclinical and clinical studies of inhaled siRNA
      therapeutics.

PMID- 24665867
TI  - Variability in clinical features of early versus late cardiovascular implantable
      electronic device pocket infections.
AB  - BACKGROUND: Cardiovascular implantable electronic device (CIED) pocket infections
      are often related to recent CIED placement or manipulation, but these infections
      are not well characterized. The clinical presentation of CIED pocket infection,
      based on temporal onset related to last CIED procedure, deserves further study.
      METHODS: The MEDIC (Multicenter Electrophysiologic Device Infection Cohort)
      prospectively enrolled subjects with CIED infection. Subjects were stratified
      into those whose infection occurred <12 months (early) or >= 12 months (late)
      since their last CIED-related procedure. RESULTS: There were 132 subjects in the
      early group and 106 in the late group. There were more females (P = 0.009) and
      anticoagulation use (P = 0.039) in the early group. Subjects with early
      infections were more likely to have had a generator change or lead addition as
      their last procedure (P = 0.03) and had more prior CIED procedures (P = 0.023).
      Early infections were more likely to present with pocket erythema (P < 0.001),
      swelling (P < 0.001), and pain (P = 0.007). Late infections were more likely to
      have pocket erosion (P = 0.005) and valvular vegetations (P = 0.009). In
      bacteremic subjects, early infections were more likely healthcare-associated (P <
      0.001). In-hospital and 6-month mortality were equivalent. CONCLUSION: A total of
      45% of patients with CIED pocket infection presented >12 months following their
      last CIED-related procedure. Patients with early infection were more likely to be
      female, on anticoagulation, and present with localized inflammation, whereas
      those with late infection were more likely to have CIED erosion or valvular
      endocarditis.

PMID- 24665868
TI  - Increased risk of rhinitis symptoms in subjects with gastroesophageal reflux.
AB  - CONCLUSION: This study shows that gastroesophageal reflux and tobacco smoke are
      associated with adult-onset non-infectious rhinitis (NIR). The results support an
      association between gastroesophageal reflux and upper airway inflammation.
      OBJECTIVES: To examine the incidence of adult-onset NIR in relation to several
      risk factors. METHODS: This is a follow-up study of 3307 randomly selected men
      and women aged 25-75 years from a general population-based sample. At baseline,
      the subjects were investigated with questionnaires, a pulmonary function test,
      blood samples, and FENO. At follow-up 4 years later, all the subjects were mailed
      a respiratory questionnaire. The incidence of NIR and associated risk factors,
      such as smoking, atopy, asthma, cough, obesity, and gastroesophageal reflux, was
      assessed. RESULTS: The response rate at follow-up was 92%. The incidence of new
      onset NIR was 14.9/1000 person-years (n = 247). In a regression model including
      age, gender, obesity, asthma, cough, and atopy, both current smoking (OR 1.7, 95%
      CI 1.2-2.5, p = 0.002) and gastroesophageal reflux (OR 2.5, 95% CI 1.4-3.1, p <
      0.001) were significantly associated with adult-onset NIR.

PMID- 24665869
TI  - Starting to develop self-help for social anxiety associated with vitiligo: using
      clinical significance to measure the potential effectiveness of enhanced
      psychological self-help.
AB  - BACKGROUND: Vitiligo can be associated with high levels of distress, yet there
      are currently no self-help interventions available. OBJECTIVES: To describe the
      initial development of a psychosocial self-help intervention designed to reduce
      social anxiety associated with vitiligo. Also to examine whether including a
      planning exercise, aimed at increasing use of the intervention (termed
      implementation intentions), has the potential to achieve a clinically significant
      reduction in distress. METHODS: Participants (n = 75) were randomized to one of
      three groups: cognitive behavioural self-help (CBSH), CBSH augmented with
      implementation intentions (CBSH+), or no intervention. Participants were assessed
      at baseline and after 8 weeks on measures of social anxiety, anxiety and
      depression, and appearance-related concern. The two intervention groups also
      completed a questionnaire evaluating their use of, and satisfaction with, the
      intervention. RESULTS: High levels of social anxiety and concern over appearance
      were reported. Twenty-four per cent of participants in the CBSH+ group
      experienced clinically significant change on the measure of social anxiety
      compared with 8% in the CBSH group and 0% in the control group. In addition, 58%
      of the control group deteriorated during the study period. There were no
      significant differences between the conditions on the other outcome measures.
      Participants reported that the self-help leaflets were helpful. CONCLUSIONS: The
      findings demonstrate that augmented CBSH provides a relatively simple and
      accessible intervention that can result in a clinically significant reduction in
      social anxiety. The augmented intervention has potential and might be further
      developed and evaluated in subsequent trials.

PMID- 24665870
TI  - Two novel lignans from Gaultheria yunnanensis.
AB  - Two new lignans, 9-salicyl-(+)-isolariciresinol (1) and gaultheroside G (2),
      together with seven known compounds, were isolated from the ethanolic extract of
      the whole plant of Gaultheria yunnanensis. Their structures were determined by
      extensive NMR and MS analyses. Gaultheroside G (2) was found to have an unusual
      ether linkage between the 2 and 9' positions of aryl-tetralin lignan skeleton.
      All nine compounds were assayed for inhibitory effects against nitric oxide and
      pro-inflammatory cytokines TNF-alpha and IL-6 release in LPS-induced RAW 246.7
      macrophages, while no significant activities were observed for the evaluated
      compounds. 

PMID- 24665871
TI  - Ozone as an adjunct to conventional nonsurgical therapy in chronic periodontitis:
      a randomized controlled clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Currently, only limited data are available from
      controlled clinical trials regarding the effect of irrigation by ozonated water
      in the treatment of periodontitis. The aim of the present study was to determine
      the clinical and biological effects of the adjunctive use of ozone in nonsurgical
      periodontal treatment. MATERIAL AND METHODS: Forty-one patients with chronic
      periodontitis were randomized to treatment with either subgingival scaling and
      root planing (SRP) followed by irrigation with ozonated water (test) or
      subgingival SRP followed by irrigation with distilled water irrigation (control).
      The following parameters were evaluated at baseline (T0), 3 mo (T1): plaque
      index; gingival index; bleeding on probing; probing pocket depth; gingival
      recession; and clinical attachment loss. In addition, the serum concentrations of
      high sensitivity C-reactive protein were measured at T0 and T1. RESULTS: Forty
      one patients with chronic periodontitis were included in the analysis (20 in the
      test group and 21 in the control group). There was statistically significant
      improvement in the study parameters in both groups between T0 and T1, except for
      gingival index. However, there were no significant differences in any study
      parameter between test and control groups. CONCLUSION: Irrigation with ozonated
      water as an adjunctive therapy to SRP produces no statistically significant
      benefit compared with SRP plus distilled water irrigation.

PMID- 24665872
TI  - The virtual patient in dental medicine.
AB  - OBJECTIVES: The aim of this Short Communication was to present a workflow for the
      superimposition of intraoral scan (IOS), cone-beam computed tomography (CBCT),
      and extraoral face scan (EOS) creating a 3D virtual dental patient. MATERIAL AND
      METHODS: As a proof-of-principle, full arch IOS, preoperative CBCT, and mimic EOS
      were taken and superimposed to a unique 3D data pool. The connecting link between
      the different files was to detect existing teeth as constant landmarks in all
      three data sets. RESULTS: This novel application technique successfully
      demonstrated the feasibility of building a craniofacial virtual model by image
      fusion of IOS, CBCT, and EOS under 3D static conditions. CONCLUSIONS: The
      presented application is the first approach that realized the fusion of intraoral
      and facial surfaces combined with skeletal anatomy imaging. This novel 3D
      superimposition technique allowed the simulation of treatment planning, the
      exploration of the patients' expectations, and the implementation as an effective
      communication tool. The next step will be the development of a real-time 4D
      virtual patient in motion.

PMID- 24665874
TI  - CTLA-4 gene and the susceptibility of multiple sclerosis: an updated meta
      analysis study including 12,916 cases and 15,455 controls.
AB  - Abstract Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface molecule
      involved in the regulation of T cells. Single-nucleotide polymorphisms (SNPs) of
      CTLA-4 gene are known to be associated with susceptibility to several autoimmune
      diseases, including multiple sclerosis (MS). This study aimed to evaluate the
      association between CTLA-4 and the risk of MS. Comprehensive meta-analysis was
      applied to case-control studies of the association between MS and CTLA-4 to
      assess the joint evidence for the association, the influence of individual
      studies, and evidence for publication bias. The authors searched PubMed, MEDLINE,
      Cochrane Library, and reference lists of relevant studies to September 2013. In
      all, the allele or genotype analysis showed no significant association between +
      49A/G, - 318C/T, or CT60A/G and MS. And the subgroups of the three polymorphisms
      divided into Americas, Europe, and Asia showed no significant association with
      MS. The sensitivity analysis or publication bias analysis showed no significance.
      In conclusion, this comprehensive meta-analysis suggested that + 49A/G, - 318C/T,
      or CT60A/G polymorphism, either in total analysis or in subgroup analyses, has no
      significant association with MS disease. 

PMID- 24665873
TI  - Maternal infant feeding behaviors and disparities in early child obesity.
AB  - BACKGROUND: Although disparities in child obesity exist during infancy, the
      underlying mechanisms are unclear. Assessing dissimilarities in feeding
      practices, styles, and beliefs may provide a better understanding of these
      mechanisms. This study sought to identify modifiable maternal-infant feeding
      behaviors that may contribute to disparities in early child obesity. METHODS:
      This study is a cross-sectional analysis comparing mothers with infants (2 weeks
      to 6 months old) in a low-risk group of high-income white mothers to a high-risk
      group of low-income Hispanic mothers. Regression analysis was used to explore
      relationships between each group and (1) infant feeding practices, including
      breastfeeding, giving juice, and adding cereal to bottles, (2) controlling
      feeding styles, (3) beliefs about infant hunger and satiety, and (4) infant
      weight status. RESULTS: The sample included 412 mothers (low-risk group, n = 208;
      high-risk group, n = 204). The high-risk group was less likely to exclusively
      breastfeed (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.22
      0.83), more likely to introduce juice (AOR, 12.25; 95% CI, 3.44-43.62), and add
      cereal to the bottle (AOR, 10.61; 95% CI, 2.74-41.0). The high-risk group
      exhibited greater restrictive and pressuring feeding styles and was more likely
      to believe that mothers can recognize infant hunger and satiety and less likely
      to believe that infants know their own hunger and satiety. High-risk infants were
      more likely to have a weight-for-length percentile >85th percentile (AOR, 2.66;
      95% CI, 1.10-6.45). CONCLUSIONS: Differences in infant feeding behaviors may
      contribute to disparities in early child obesity. Longitudinal studies are needed
      to determine the effect of these differences on child obesity.

PMID- 24665875
TI  - Biohydrogenation of fatty acids is dependent on plant species and feeding regimen
      of dairy cows.
AB  - Rumen biohydrogenation (BH) of C18:3n-3 (ALA) and C18:2n-6 (LA) has been shown to
      be reduced in cows fed species-rich herbage, but plant species offering the best
      protection against BH are yet to be elucidated. The aim of the present study was
      to investigate differences in rumen in vitro BH of ALA and LA between single
      plant species and feeding regimens. Rumen fluid was collected from cows fed
      either total mixed ration (TMR), species-rich silage (HERB), or grass silage
      (GRASS). Five single species (alfalfa, birdsfoot trefoil, chicory, English
      plantain, and salad burnet) and a grass-clover mixture (white clover and
      ryegrass) were incubated in three replicas up to 30 h and subsequently analyzed
      for fatty acid content. Michaelis-Menten kinetics was applied for quantifying the
      BH rate. BH proceeded at the lowest rate in alfalfa and salad burnet (P < 0.005),
      and independent of species BH rate was lower in HERB and GRASS compared to TMR (P
      < 0.001). 

PMID- 24665876
TI  - Mycoplasma pneumoniae-associated mucositis--case report and systematic review of
      literature.
AB  - BACKGROUND: Mycoplasma pneumoniae, a bacterium known to be a common cause of
      pneumonia, has been documented to cause complications such as debilitating
      mucositis previously described as an atypical Stevens-Johnson syndrome without
      skin lesions. However, in the spectrum of epidermal dermatopathies, the condition
      is increasingly recognized as a separate entity, now termed M. pneumoniae
      associated mucositis (MPAM). OBJECTIVES: We present a case of MPAM and
      systemically review the literature to discuss diagnostic and therapeutic options.
      METHODS: A systematic literature search was performed to find studies reporting
      MPAM in adults. We extracted and analysed patient demographics, disease
      symptomatology, diagnostic testing and treatment. RESULTS: Eleven articles,
      describing 12 patients and our own patient met the predefined criteria and were
      analysed. Respiratory, ocular and oral symptoms were present in all patients.
      Therapies predominantly included antibiotics (10 of 13) and immunosuppressive
      treatment (9 of 13) leading to complete resolution of symptoms in all patients.
      CONCLUSION: Our findings highlight that MPAM should be recognized as a distinct
      disease entity within the spectrum of epidermal dermatopathies. We discuss and
      show in our patient why M. pneumoniae IgA serum levels could prove to be more
      reliable diagnostic tools in the MPAM diagnosis than the widely used IgG and IgM
      titre levels.

PMID- 24665877
TI  - Possible association of FAS and FASLG polymorphisms with the risk of idiopathic
      azoospermia in southeast Turkey.
AB  - To investigate the association of the genetic variants of FAS/FASLG cell death
      pathway genes in male infertility, we genotyped the FAS -670A/G, -1377G/A, and
      FASLG -124A/G single-nucleotide polymorphisms (SNPs) by real-time polymerase
      chain reaction in 108 infertile men with idiopathic azoospermia and in 125 proven
      fertile controls. The distribution of genotypes and alleles for SNPs at FAS 
      1377G/A and FASLG -124A/G loci were determined not to be statistically different
      between the case and control groups. However, the genotype frequencies of SNPs,
      FAS -670AA and FAS -670AG, were found to be significantly different between the
      case and control groups. Whereas the FAS -670AA genotype might be regarded as a
      higher predisposition for idiopathic azoospermia, FAS -670AG could be interpreted
      to mean that this genotype provides protection against idiopathic azoospermia.
      The study of combined genotype and haplotype frequencies has found statistically
      significant differences between case and control subjects for some combinations.
      The AA-GG binary genotype for the FAS670 and FAS1377 loci couple, in particular,
      may have a high degree of predisposition to idiopathic azoospermia. Our results
      suggest that FAS -670A/G SNP may be a genetic predisposing factor of idiopathic
      azoospermia among southeastern Anatolian men. Larger studies are needed to verify
      these findings. Furthermore, our data indicated a possible linkage between the
      FAS and FASLG genes and idiopathic azoospermia. 

PMID- 24665878
TI  - Serum levels of malondialdehyde, vitamin C and E in idiopathic nephrotic
      syndrome: a meta-analysis.
AB  - It is well documented that oxidative stress is involved in the pathogenesis of
      idiopathic nephrotic syndrome (INS). Malondialdehyde (MDA) is a measurement of
      lipid oxidation; vitamin C and E are important components of antioxidants.
      However, the association between MDA, vitamin C or E levels and INS remains
      elusive. A meta-analysis was performed to investigate the alteration of serum
      levels of MDA, vitamin C and E in INS compared with controls. Eight studies were
      included in our meta-analysis according to predefined criteria. Active INS
      patients demonstrated significantly higher level of serum MDA (SMD: 2.13, 95% CI:
      1.511 to 2.749, p < 10(-4)), markedly lower levels of serum vitamin C (SMD: 
      1.449, 95% CI: -2.616 to -0.281, p = 0.015) and E (SMD: -1.45, 95% CI: -2.544 to 
      0.356, p = 0.009) compared with those in controls. Active steroid-sensitive
      nephrotic syndrome (SSNS) patients showed comparable levels of serum vitamin C
      and E to those in controls. INS subjects in the remission stage demonstrated
      significantly higher level of serum MDA (SMD: 1.028, 95% CI: 0.438 to 1.617, p <
      10(-4)), markedly lower level of serum vitamin C (SMD: -2.235, 95% CI: -3.048 to 
      1.421, p < 10(4)) and similar level of serum vitamin E compared with those in
      controls. No significant publication bias was observed. In conclusion, the
      disorder of MDA and vitamin C persists in the remission stage of INS. It seems
      that the serum levels of vitamin C and E is associated with the responsiveness of
      INS to steroids. However, more studies should be performed in the future.

PMID- 24665879
TI  - Effects of temperature change on cortisol release by common carp Cyprinus carpio.
AB  - Common carp Cyprinus carpio, stressed by fish handling practices, responded with
      a decrease in cortisol secretion when temperature was lowered from 20 to 14
      degrees  C within 3.5 h compared to those kept at 20 degrees  C. 

PMID- 24665880
TI  - Personalized ophthalmology.
AB  - Ophthalmology has been an early adopter of personalized medicine. Drawing on
      genomic advances to improve molecular diagnosis, such as next-generation
      sequencing, and basic and translational research to develop novel therapies,
      application of genetic technologies in ophthalmology now heralds development of
      gene replacement therapies for some inherited monogenic eye diseases. It also
      promises to alter prediction, diagnosis and management of the complex disease age
      related macular degeneration. Personalized ophthalmology is underpinned by an
      understanding of the molecular basis of eye disease. Two important areas of focus
      are required for adoption of personalized approaches: disease stratification and
      individualization. Disease stratification relies on phenotypic and genetic
      assessment leading to molecular diagnosis; individualization encompasses all
      aspects of patient management from optimized genetic counseling and conventional
      therapies to trials of novel DNA-based therapies. This review discusses the
      clinical implications of these twin strategies. Advantages and implications of
      genetic testing for patients with inherited eye diseases, choice of molecular
      diagnostic modality, drivers for adoption of personalized ophthalmology, service
      planning implications, ethical considerations and future challenges are
      considered. Indeed, whilst many difficulties remain, personalized ophthalmology
      truly has the potential to revolutionize the specialty.

PMID- 24665882
TI  - delta-Deuterium isotope effects as probes for transition-state structures of
      isoprenoid substrates.
AB  - The biosynthetic pathways to isoprenoid compounds involve transfer of the prenyl
      moiety in allylic diphosphates to electron-rich (nucleophilic) acceptors. The
      acceptors can be many types of nucleophiles, while the allylic diphosphates only
      differ in the number of isoprene units and stereochemistry of the double bonds in
      the hydrocarbon moieties. Because of the wide range of nucleophilicities of
      naturally occurring acceptors, the mechanism for prenyltransfer reactions may be
      dissociative or associative with early to late transition states. We have
      measured delta-secondary kinetic isotope effects operating through four bonds for
      substitution reactions with dimethylallyl derivatives bearing deuterated methyl
      groups at the distal (C3) carbon atom in the double bond under dissociative and
      associative conditions. Computational studies with density functional theory
      indicate that the magnitudes of the isotope effects correlate with the extent of
      bond formation between the allylic moiety and the electron-rich acceptor in the
      transition state for alkylation and provide insights into the structures of the
      transition states for associative and dissociative alkylation reactions.

PMID- 24665881
TI  - Identifying ligand-specific signalling within biased responses: focus on delta
      opioid receptor ligands.
AB  - Opioids activate GPCRs to produce powerful analgesic actions but at the same time
      induce side effects and generate tolerance, which restrict their clinical use.
      Reducing this undesired response profile has remained a major goal of opioid
      research and the notion of 'biased agonism' is raising increasing interest as a
      means of separating therapeutic responses from unwanted side effects. However, to
      fully exploit this opportunity, it is necessary to confidently identify biased
      signals and evaluate which type of bias may support analgesia and which may lead
      to undesired effects. The development of new computational tools has made it
      possible to quantify ligand-dependent signalling and discriminate this component
      from confounders that may also yield biased responses. Here, we analyse different
      approaches to identify and quantify ligand-dependent bias and review different
      types of confounders. Focus is on delta opioid receptor ligands, which are
      currently viewed as promising agents for chronic pain management. LINKED
      ARTICLES: This article is part of a themed section on Opioids: New Pathways to
      Functional Selectivity. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24665883
TI  - Growth and self-assembly of ultrathin Au nanowires into expanded hexagonal
      superlattice studied by in situ SAXS.
AB  - We report the self-assembly of gold nanowires into hexagonal superlattices in
      liquid phase followed by in situ small-angle X-ray scattering and give new
      insights into their growth mechanism. The unprecedented large interwire distance
      of 8 nm strongly suggests the stabilization of the ultrathin gold nanowires by a
      ligand's double layer composed of oleylamine and oleylammonium chloride. The one
      dimensional growth is discussed, opening perspectives toward the control growth
      and self-assemblies of metallic nanowires. 

PMID- 24665884
TI  - Breakdown of the energy gap law in molecular lanthanoid luminescence: the
      smallest energy gap is not universally relevant for nonradiative deactivation.
AB  - For several decades, the energy gap law has been the prevalent theoretical
      framework for the discussion of nonradiative deactivation of lanthanoid
      luminescence in molecular coordination chemistry. Here we show experimentally on
      samarium and dysprosium model complexes that the size of the energy gap DeltaE
      between a lanthanoid emitting state and the next-lower electronic state cannot be
      considered a reliable and accurate predictor of the quantitative extent of
      nonradiative deactivation by aromatic C-H and C-D oscillator overtones. Because
      the energy gap is the central pillar for the entire conceptual framework of the
      energy gap law, this finding amounts to largely invalidating this theory for the
      quantitative description of molecular multiphonon relaxation. 

PMID- 24665885
TI  - Functions of self-assembled ultrafine TiO2 nanocrystals for high efficient dye
      sensitized solar cells.
AB  - In this paper, we demonstrate a simple approach of self-assembled process to form
      a very smooth and compacted TiO2 underlayer film from ultrafine titanium oxide
      (TiO2) nanocrystals with dimension of 4 nm for improving the electrical
      properties and device performances of dye-sensitized solar cells (DSSCs). Because
      the TiO2 film self-assembles by simply casting the TiO2 on fluorine-doped tin
      oxide (FTO) substrate, it can save a lot of materials in the process. As compared
      with control DSSC without the self-assembled TiO2 (SA-TiO2) layer, short-circuit
      current density (Jsc) improves from 14.9 mA/cm(2) for control DSSC to 17.3
      mA/cm(2) for masked DSSC with the SA-TiO2 layer. With the very smooth SA-TiO2
      layer, the power conversion efficiency is enhanced from 8.22% (control) to 9.35%
      for the DSSCs with mask and from 9.79% (control) to 11.87% for the DSSCs without
      mask. To explain the improvement, we have studied the optical properties,
      morphology, and workfunction of the SA-TiO2 layer on FTO substrate as well as the
      impedance spectrum of DSSCs. Importantly, we find that the SA-TiO2 layers have
      better morphology, uniformity, and contact with FTO electrode, increased
      workfunction and optical transmission, as well as reduced charge recombination at
      the contact of FTO substrate contributing to the improved device performances.
      Consequently, our results show that the simple self-assembly of TiO2 ultrafine
      nanocrystals forms a very good electron extraction layer with both improved
      optical and electrical properties for enhancing performances of DSSCs. 

PMID- 24665886
TI  - Survival analysis of brackets and tubes: A twelve-month assessment.
AB  - OBJECTIVE: To compare the clinical performance of brackets bonded to anterior and
      posterior teeth, including second molars. MATERIALS AND METHODS: One operator,
      using the straight-wire technique, bonded metallic brackets to the teeth of 127
      consecutive patients. All patients were observed for 12 months during their
      regular orthodontic appointments. Bracket failures were recorded and summarized
      for statistical analysis. The Cox proportional hazards regression analysis was
      performed to evaluate bracket failure rates. RESULTS: Statistically significant
      differences in survival rates were observed between molar tubes and anterior
      brackets (P < .05). Twelve-month failure rates of incisor, canine, premolar, and
      molar brackets were 3.6, 1.6, 4.8, and 11.6%, respectively. The first and second
      molar did not show significant difference in bond failure. Young patients (age
      <18 years) showed a higher failure rate than old patients (>=18 years).
      CONCLUSIONS: Brackets directly bonded to the buccal surfaces of molars failed
      significantly more often than those directly bonded to anterior teeth or
      premolars, but showed acceptable failure rate especially in adult patients.
      Bonding on second molars seems to be as reliable as bonding on the first molars.

PMID- 24665887
TI  - Treatment and posttreatment effects induced by the Forsus appliance: A controlled
      clinical study.
AB  - OBJECTIVE: To evaluate treatment and posttreatment dentoskeletal effects induced
      by the Forsus device (FRD) in growing patients with Class II malocclusion in a
      retrospective controlled clinical study. MATERIALS AND METHODS: Thirty-six Class
      II patients (mean [SD] age 12.3 [1.2] years) were treated consecutively with the
      FRD protocol and compared with a sample of 20 subjects with untreated Class II
      malocclusion (mean [SD] age 12.2 [0.9] years). Lateral cephalograms were taken at
      the beginning of treatment, at the end of comprehensive treatment (after 2.3 +/-
      0.4 years), and at a postretention period (after 2.3 +/- 1.1 years from the end
      of comprehensive treatment). Statistical comparisons were carried out with the
      unpaired t-test and Benjamini-Hochberg correction (P < .05). RESULTS: After
      comprehensive treatment, the FRD sample showed a significant restriction of the
      sagittal maxillary growth together with a significant correction in overjet,
      overbite, and molar relationship. During the overall observation interval, the
      FRD group exhibited no significant sagittal or vertical skeletal changes, while
      significant improvements were recorded in overjet (-3.8 mm), overbite (-1.5 mm),
      and molar relationship (+3.7 mm). CONCLUSION: The FRD protocol was effective in
      correcting Class II malocclusion mainly at the dentoalveolar level when evaluated
      2 years after the end of comprehensive treatment.

PMID- 24665888
TI  - Assessment of pharyngeal airway volume in adolescent patients affected by
      bilateral cleft lip and palate using cone beam computed tomography.
AB  - OBJECTIVE: To test the null hypothesis that there were no significant differences
      for pharyngeal airway volumes between the adolescent patients affected by
      bilateral cleft lip and palate (BCLP) and well-matched controls using cone beam
      computed tomography. MATERIALS AND METHODS: The study sample consisted of 16
      patients (11 female and 5 male; mean [SD] age 14.1 [2.1] years) affected by BCLP
      and 16 patients (10 female and 6 male; mean [SD] age 13.4 [2.0] years) as age-
      and sex-matched control group. Craniofacial measurements and pharyngeal airway
      dimension, area, and volume measurements of patients in both groups were
      calculated and statistically examined using Student's t-test and multiple linear
      regression analyses. RESULTS: Statistically significant differences were found
      between the BCLP and control groups for SNB (P < .05), SN-GoGn (P < .05), Co-A (P
      < .05), PAS (P < .01), minAx (P < .01), and oropharyngeal airway volume (P <
      .05). The most predictive variables for oropharyngeal airway volume were found as
      PAS (r  =  .655 and P  =  .000) and minAx (r  =  .787 and P  =  .000).
      CONCLUSIONS: The null hypothesis was rejected. Oropharyngeal (P < .05) and total
      (P > .05) airway volumes were found to be less in the BCLP group, and thus the
      treatment choice in these patients should have positive effects on the pharyngeal
      airway.

PMID- 24665889
TI  - Role of lubricants on friction between self-ligating brackets and archwires.
AB  - OBJECTIVE: To evaluate the effect of different lubricants on friction between
      orthodontic brackets and archwires. MATERIALS AND METHODS: Active (Quick,
      Forestadent) and passive (Damon 3MX, Ormco) self-ligating brackets underwent
      friction tests in the presence of mucin- and carboxymethylcellulose (CMC)-based
      artificial saliva, distilled water, and whole human saliva (positive control).
      Dry friction (no lubricant) was used as the negative control. Bracket/wire
      samples (0.014 * 0.025 inch, CuNiTi, SDS Ormco) underwent friction tests eight
      times in a universal testing machine. RESULTS: Two-way analysis of variance
      showed no significant interaction between bracket type and lubricant (P  = 
      .324). Friction force obtained with passive self-ligating brackets was lower than
      that for active brackets (P < .001). Friction observed in the presence of
      artificial saliva did not differ from that generated under lubrication with
      natural human saliva, as shown by Tukey test. Higher friction forces were found
      with the use of distilled water or when the test was performed under dry
      condition (ie, with no lubricant). CONCLUSION: Lubrication plays a role in
      friction forces between self-ligating brackets and CuNiTi wires, with mucin- and
      CMC-based artificial saliva providing a reliable alternative to human natural
      saliva.

PMID- 24665890
TI  - Paraneoplastic immune-mediated neurological effects of systemic cancers.
AB  - Cancer patients may develop paraneoplastic neurological conditions associated
      with autoantibodies directed against neural or neuromuscular tissues. These
      syndromes are frequently manifested in advance of the cancer presentation by
      several months or years necessitating a detailed and expensive investigation to
      search for the presence of a malignancy. In such cases additional assistance may
      be obtained by the early employment of whole body 18F flurodeoxyglucose positron
      emission tomography as a cancer screening imaging procedure for early cancer
      diagnosis and potential therapy. Effective therapy of the primary cancer consists
      the best current therapy for a given paraneoplastic syndrome. However, other
      forms of immune modulation, such as plasma exchange, intravenous gamma globulin,
      other immune therapies and symptomatic treatment for certain PNS may have
      additional benefit.

PMID- 24665891
TI  - Unintended cultivation, shifting baselines, and conflict between objectives for
      fisheries and conservation.
AB  - The effects of fisheries on marine ecosystems, and their capacity to drive shifts
      in ecosystem states, have been widely documented. Less well appreciated is that
      some commercially valuable species respond positively to fishing-induced
      ecosystem change and can become important fisheries resources in modified
      ecosystems. Thus, the ecological effects of one fishery can unintentionally
      increase the abundance and productivity of other fished species (i.e.,
      cultivate). We reviewed examples of this effect in the peer-reviewed literature.
      We found 2 underlying ecosystem drivers of the effect: trophic release of prey
      species when predators are overfished and habitat change. Key ecological, social,
      and economic conditions required for one fishery to unintentionally cultivate
      another include strong top-down control of prey by predators, the value of the
      new fishery, and the capacity of fishers to adapt to a new fishery. These
      unintended cultivation effects imply strong trade-offs between short-term fishery
      success and conservation efforts to restore ecosystems toward baseline conditions
      because goals for fisheries and conservation may be incompatible. Conflicts are
      likely to be exacerbated if fisheries baselines shift relative to conservation
      baselines and there is investment in the new fishery. However, in the long-term,
      restoration toward ecosystem baselines may often benefit both fishery and
      conservation goals. Unintended cultivation can be identified and predicted using
      a combination of time-series data, dietary studies, models of food webs, and
      socioeconomic data. Identifying unintended cultivation is necessary for
      management to set compatible goals for fisheries and conservation.

PMID- 24665892
TI  - Ultrasound-guided venous puncture in electrophysiological procedures: a safe
      method, rapidly learned.
AB  - BACKGROUND: We sought to determine the feasibility and learning curve associated
      with systematic use of real-time ultrasound-guided venous puncture (UGVP) in
      patients undergoing electrophysiological (EP) procedures. METHODS: Four operators
      performed UGVP in consecutive patients undergoing EP procedures (group I).
      Puncture time was defined as the time from ultrasound (US) visualization of the
      femoral vein to the insertion of all sheaths. A learning curve as defined by UGVP
      evolution over the time was established for each operator. This population was
      compared to an historical group of patients in whom venous puncture was performed
      without US (group II). RESULTS: A total of 150 patients per group were included.
      UGVP was successfully achieved in all patients. Mean time for 2.8 +/- 0.7 sheaths
      per patient insertion was 280 +/- 151 seconds in group I. There was one minor
      vascular complication (VC) out of 150 patients (0.66%) without major VC in group
      I as compared with group II (2% major VC and 4.6% minor VC; P < 0.05). UGVP time
      reached a plateau at the sixth patient-case for each operator; thus, learning
      curve was estimated to six patients. CONCLUSION: UGVP is a short learning curve
      technique, significantly associated with a low incidence of minor VCs. This study
      supports wide use of UGVP in patients undergoing EP procedures.

PMID- 24665893
TI  - Comparative off-host survival of larval Rocky Mountain Wood Ticks (Dermacentor
      andersoni) collected from ecologically distinct field populations.
AB  - Dermacentor andersoni (Ixodida: Ixodidae) Stiles, also known as the Rocky
      Mountain Wood Tick (RMWT), is found throughout the western United States and
      transmits pathogens of importance to human and animal health. The distributions
      and activity patterns of RMWTs are shaped by regional climatic variation.
      However, it is unknown if responses to climatic variation differ across the
      tick's geographical range. The objective of this narrow study was to test the
      hypothesis that the responses of RMWTs to abiotic conditions [e.g. temperature
      and RH (relative humidity)] vary among populations. We collected RMWTs from
      ecologically distinct field sites in the states of Montana and Oregon (USA). In
      the laboratory, we tracked weekly survival of tick larvae under four combinations
      of RH (75% and 98%) and temperature (26 and 32  degrees C) that reflected the
      range of conditions observed in the source habitats during spring-summer. For
      both populations, larval survival time decreased at the higher ambient
      temperature (50% mortality 1-2 weeks earlier). Differences in RH did not affect
      the survival time of larvae from Oregon. By contrast, the survival time of larvae
      from Montana decreased at the lower RH (50% mortality 1 week earlier). These data
      suggest that the tolerance limits for water stress may differ among populations
      of D. andersoni. 

PMID- 24665894
TI  - Combined alkaline hydrolysis and ultrasound-assisted extraction for the release
      of nonextractable phenolics from cauliflower (Brassica oleracea var. botrytis)
      waste.
AB  - Cauliflower waste contains high amounts phenolic compounds, but conventional
      solvent extraction misses high amounts of nonextractable phenolics (NEP), which
      may contribute more to the valorization of these waste streams. In this study,
      the NEP content and composition of cauliflower waste were investigated. The
      ability of alkaline hydrolysis, sonication, and their combination to release NEP
      was assessed. Alkaline hydrolysis with sonication was found to extract the
      highest NEP content (7.3 +/- 0.17 mg gallic acid equivalents (GAE)/g dry waste),
      which was higher than the extractable fraction. The highest yield was obtained
      after treatment of 2 M NaOH at 60  degrees C for 30 min of sonication.
      Quantification and identification were done using U(H)PLC-DAD and U(H)PLC-ESI
      MS(E). Kaempferol and quercetin glucosides along with several phenolic acids were
      found. The results of the study show that there are higher amounts of valuable
      health-promoting compounds from cauliflower waste than what is currently
      described in the literature. 

PMID- 24665895
TI  - Assessing the potential biological implications of recreational inshore fisheries
      on sub-tidal fish communities of Azores (north-east Atlantic Ocean) using catch
      and effort data.
AB  - Recreational inshore fishing activities practiced on Faial and Pico Islands
      (Azorean archipelago) were surveyed between October 2004 and September 2005.
      Recreational inshore fishers employ three main methods of fishing (shore angling,
      spear fishing and intertidal collecting). The method that demanded the highest
      fishing effort (number of fishing operations) was shore angling, followed by
      intertidal collecting and spear fishing. Shore angling produced the highest
      diversity of catch composition (38), which is in part explained by the seven
      fishing techniques used by shore anglers. The estimates of annual catch were
      higher for shore angling than spear fishing (51.2 and 6.3 t) even though they
      were lower than commercial artisanal fishing (442 t). The weighted mean trophic
      level and vulnerability index values in the fish catch were higher for spear
      fishing (3.4 and 50.9) than for shore angling (3.1 and 44.5). Cumulative pressure
      by different recreational fishing activities was detected on species already
      subject to a heavy pressure from Azorean commercial fishing, and on vulnerable
      and top-predator species. There are important biological and ecological
      implications whereby fishery managers should implement additional regulations
      such as prohibiting catches of the most vulnerable species. 

PMID- 24665896
TI  - TexMi: development of tissue-engineered textile-reinforced mitral valve
      prosthesis.
AB  - Mitral valve regurgitation together with aortic stenosis is the most common
      valvular heart disease in Europe and North America. Mechanical and biological
      prostheses available for mitral valve replacement have significant limitations
      such as the need of a long-term anticoagulation therapy and failure by
      calcifications. Both types are unable to remodel, self-repair, and adapt to the
      changing hemodynamic conditions. Moreover, they are mostly designed for the
      aortic position and do not reproduce the native annular-ventricular continuity,
      resulting in suboptimal hemodynamics, limited durability, and gradually
      decreasing ventricular pumping efficiency. A tissue-engineered heart valve
      specifically designed for the mitral position has the potential to overcome the
      limitations of the commercially available substitutes. For this purpose, we
      developed the TexMi, a living textile-reinforced mitral valve, which
      recapitulates the key elements of the native one: annulus, asymmetric leaflets
      (anterior and posterior), and chordae tendineae to maintain the native annular
      ventricular continuity. The tissue-engineered valve is based on a composite
      scaffold consisting of the fibrin gel as a cell carrier and a textile tubular
      structure with the twofold task of defining the gross three-dimensional (3D)
      geometry of the valve and conferring mechanical stability. The TexMi valves were
      molded with ovine umbilical vein cells and stimulated under dynamic conditions
      for 21 days in a custom-made bioreactor. Histological and immunohistological
      stainings showed remarkable tissue development with abundant aligned collagen
      fibers and elastin deposition. No cell-mediated tissue contraction occurred. This
      study presents the proof-of-principle for the realization of a tissue-engineered
      mitral valve with a simple and reliable injection molding process readily
      adaptable to the patient's anatomy and pathological situation by producing a
      patient-specific rapid prototyped mold. 

PMID- 24665897
TI  - Influence of the implant design on osseointegration and crestal bone resorption
      of immediate implants: a histomorphometric study in dogs.
AB  - PURPOSE: The aim of this study was to evaluate bone-to-implant contact after
      immediate implant placement at different levels in relation to crestal bone in
      American foxhound dogs. MATERIALS AND METHODS: The mandibular second, third, and
      fourth premolars of six American foxhound dogs were extracted bilaterally.
      Randomly, three immediate implants were placed in the hemimandible of each dog at
      the bone crest (control group) or 2 mm subcrestally (test group). Three dogs were
      allowed an 8-week healing period; the other three were left a 12-week healing
      period. After healing periods, histomorphometric analyses of the specimens were
      carried out to measure BIC values and bone remodeling. RESULTS: All implants
      healed uneventfully and were available for histological analysis. The total BIC
      mean values were 44.52% (+/- 8.67) and 39.50% (+/- 9.25) at 8 and 12 weeks,
      respectively, for the control group, and 47.33% (+/- 5.23) and 53.85% (+/- 4.21)
      at 8 and 12 weeks after healing for the test group, respectively. There was
      observed less bone resorption in the group of implants placed subcrestally.
      CONCLUSION: Our findings suggest that less resorption may be expected when
      implants are inserted 2 mm subcrestally. Moreover, higher BIC values in the group
      of subcrestal implants were found.

PMID- 24665898
TI  - Determination of interventions for upper extremity tactile impairment in children
      with cerebral palsy: a systematic review.
AB  - AIM: This study reviewed interventions suitable for treating tactile dysfunction
      in children with cerebral palsy (CP). METHOD: A systematic review was conducted
      of six databases, searched for population: ('brain injury' OR 'cerebral palsy' OR
      'stroke' OR 'cerebrovascular accident') and intervention: ('tactile' OR
      'sensation'). Inclusion criteria were: (1) published after 1950 in English; (2)
      participants older than 4 years with brain injury; (3) upper limb intervention;
      and (4) examined tactile registration or perception. RESULTS: Of 2938 studies
      identified, 30 met the inclusion criteria. Results from included studies
      indicated that tactile function improved in adults with stroke after transfer
      enhanced training (t[47]=2.75, p=0.004), stimulus specific training (p<0.001),
      ice therapy (F=5.71, p=0.028), mirror therapy (F=7.7, p=0.009), and functional
      deafferentation using an anaesthetic cream (t=3.76; p<0.01). No intervention
      reported improvement in tactile dysfunction for children with CP. INTERPRETATION:
      Research is required to develop tactile interventions for children with CP that
      integrate methodology from effective approaches for adults after stroke. Stimulus
      specific training, transfer enhanced training, and mirror therapy are promising.
      Other approaches are less suitable for children because of invasiveness
      (electrical stimulation), safety (ice therapy), or limitation of bimanual
      function (eutectic mixture of local anaesthetics, pneumatic cuff).

PMID- 24665900
TI  - Folding of an unfolded protein by macromolecular crowding in vitro.
AB  - Protein folding in vivo takes place in a highly crowded environment. The
      resulting excluded volume forces are thought to stabilize folded forms of
      proteins. In agreement, many in vitro studies have shown that the presence of
      macromolecular crowding agents increases the stability of folded proteins but
      often by only a few kJ per mol. Although it should not matter at what position in
      the transition between folded and unfolded forms the effect of crowding is
      employed, there have been no studies assessing whether excluded volume forces
      alone can correctly fold polypeptides that are mostly unfolded. However, some
      studies have indicated that the effect of crowding becomes larger the more
      destabilized the protein is (but still being folded), suggesting that the
      crowding effect may be exaggerated for unfolded proteins. To address this
      question directly, we turned to a destabilized mutant of protein L that is mostly
      unfolded in water but can be folded upon addition of salt. We find that the
      effect of 200 mg/mL Dextran 20 on the folding equilibrium constant for unfolded
      protein L (DeltaDeltaGU ~ 2 kJ mol(-1)) matches the crowding effects found on the
      folded wild type protein and the mutant when prefolded by salt. This result
      indicates that the excluded volume effect is independent of starting protein
      stability and that crowding can shift the reaction toward the folded form when
      the polypeptide is in the transition region between folded and unfolded states. 

PMID- 24665899
TI  - Elevations in vascular markers and eosinophils in chronic spontaneous urticarial
      weals with low-level persistence in uninvolved skin.
AB  - BACKGROUND: In chronic spontaneous urticaria (CSU) mast cell activation together
      with inflammatory changes in the skin are well documented and may play an
      important role in mechanisms of tissue oedema. OBJECTIVES: To confirm and extend
      these observations by measuring microvascular markers, leucocytes and mast cell
      numbers in lesional and uninvolved skin and to compare findings with a control
      group. METHODS: Paired biopsies (one from 4-8-h spontaneous weals and one from
      uninvolved skin) were taken from eight patients with CSU and nine control
      subjects and studied using immunohistochemistry and confocal microscopy using the
      lectin Ulex europaeus agglutinin 1 (UEA-1). RESULTS: Lesional skin in CSU
      contained significantly more CD31+ endothelial cells; CD31+ blood vessels,
      neutrophils, eosinophils, basophils and macrophages; and CD3+ T cells than
      nonlesional skin. Increased vascularity was confirmed by confocal imaging using
      the lectin UEA-1. Uninvolved skin from CSU contained significantly more CD31+
      endothelial cells, CD31+ blood vessels and eosinophils compared with the control
      subjects. There was a threefold increase in mast cell numbers when CSU was
      compared with controls but no difference was observed between lesional and
      uninvolved skin. CONCLUSIONS: Increased vascular markers together with eosinophil
      and neutrophil infiltration are features of lesional skin in CSU and might
      contribute to tissue oedema. Eosinophils and microvascular changes persist in
      uninvolved skin, which, together with increased mast cells, suggests that
      nonlesional skin is primed for further wealing.

PMID- 24665901
TI  - Mechanisms of the InCl3-catalyzed type-I, II, and III cycloisomerizations of 1,6
      enynes.
AB  - InCl3-catalyzed cycloisomerizations of 1,6-enynes can give either type-I dienes
      and cyclohexenes (type-III dienes), or type-II dienes, depending on the
      substitutions in the substrates. Previously, we studied how the type-II diene
      products were generated and found that the real catalytic species for the
      cycloisomerizations is InCl2(+) (J. Org. Chem. 2012, 77, 8527-8540). In the
      present paper, we used density functional theory (DFT) calculations to reveal how
      the type-I and type-III dienes were generated. A unified model to explain how
      substituents affect the regiochemistry of type-I, II, and III cycloisomerizations
      has been provided. Experimental and computational investigation of the InCl3
      catalyzed cycloisomerization of 1,6-enynes with both substituents at the alkyne
      and alkene parts has also been reported in the present study. 

PMID- 24665902
TI  - Computational disease gene prioritization: an appraisal.
AB  - Bioinformatics aids in the understanding of the biological processes of living
      beings and the genetic architecture of human diseases. The discovery of disease
      related genes improves the diagnosis and therapy design for the disease. To save
      the cost and time involved in the experimental verification of the candidate
      genes, computational methods are employed for ranking the genes according to
      their likelihood of being associated with the disease. Only top-ranked genes are
      then verified experimentally. A variety of methods have been conceived by the
      researchers for the prioritization of the disease candidate genes, which differ
      in the data source being used or the scoring function used for ranking the genes.
      A review of various aspects of computational disease gene prioritization and its
      research issues is presented in this article. The aspects covered are gene
      prioritization process, data sources used, types of prioritization methods, and
      performance assessment methods. This article provides a brief overview and acts
      as a quick guide for disease gene prioritization.

PMID- 24665903
TI  - A small-molecule benzimidazole derivative that potently activates AMPK to
      increase glucose transport in skeletal muscle: comparison with effects of
      contraction and other AMPK activators.
AB  - AMPK (AMP-activated protein kinase) is an attractive therapeutic drug target for
      treating metabolic disorders. We studied the effects of an AMPK activator
      developed by Merck (ex229 from patent application WO2010036613), comparing
      chemical activation with contraction in intact incubated skeletal muscles. We
      also compared effects of ex229 with those of the Abbott A769662 compound and
      AICAR (5-amino-4-imidazolecarboxamide riboside). In rat epitrochlearis muscle,
      ex229 dose-dependently increased AMPK activity of alpha1-, alpha2-, beta1- and
      beta2-containing complexes with significant increases in AMPK activity seen at a
      concentration of 50 MUM. At a concentration of 100 MUM, AMPK activation was
      similar to that observed after contraction and importantly led to an ~2-fold
      increase in glucose uptake. In AMPK alpha1-/alpha2-catalytic subunit double
      knockout myotubes incubated with ex229, the increases in glucose uptake and ACC
      (acetyl-CoA carboxylase) phosphorylation seen in control cells were completely
      abolished, suggesting that the effects of the compound were AMPK-dependent. When
      muscle glycogen levels were reduced by ~50% after starvation, ex229-induced AMPK
      activation and glucose uptake were amplified in a wortmannin-independent manner.
      In L6 myotubes incubated with ex229, fatty acid oxidation was increased.
      Furthermore, in mouse EDL (extensor digitorum longus) and soleus muscles, ex229
      increased both AMPK activity and glucose uptake at least 2-fold. In summary,
      ex229 efficiently activated skeletal muscle AMPK and elicited metabolic effects
      in muscle appropriate for treating Type 2 diabetes by stimulating glucose uptake
      and increasing fatty acid oxidation.

PMID- 24665904
TI  - Methylisothiazolinone: a case of perianal dermatitis caused by wet wipes and
      review of an emerging pediatric allergen.
AB  - Methylisothiazolinone (MI) is a preservative found in cosmetic, personal hygiene,
      and industrial products. It has been characterized as a moderate to strong
      sensitizer and is an emerging allergen in the pediatric population. We discuss a
      case of perianal dermatitis in a child caused by contact allergy to MI-containing
      wet wipes. 

PMID- 24665905
TI  - Oxidative changes and apoptosis induced by 1800-MHz electromagnetic radiation in
      NIH/3T3 cells.
AB  - To investigate the potential adverse effects of mobile phone radiation, we
      studied reactive oxygen species (ROS), DNA damage and apoptosis in mouse
      embryonic fibroblasts (NIH/3T3) after intermittent exposure (5 min on/10 min off,
      for various durations from 0.5 to 8 h) to an 1800-MHz GSM-talk mode
      electromagnetic radiation (EMR) at an average specific absorption rate of 2 W/kg.
      A 2',7'-dichlorofluorescin diacetate fluorescence probe was used to detect
      intracellular ROS levels, immunofluorescence was used to detect gammaH2AX foci as
      a marker for DNA damage, and flow cytometry was used to measure apoptosis. Our
      results showed a significant increase in intracellular ROS levels after EMR
      exposure and it reached the highest level at an exposure time of 1 h (p < 0.05)
      followed by a slight decrease when the exposure continued for as long as 8 h. No
      significant effect on the number of gammaH2AX was detected after EMR exposure.
      The percentage of late-apoptotic cells in the EMR-exposed group was significantly
      higher than that in the sham-exposed groups (p < 0.05). These results indicate
      that an 1800-MHz EMR enhances ROS formation and promotes apoptosis in NIH/3T3
      cells.

PMID- 24665906
TI  - Good thermoelectric performance in strongly correlated system SnCCo3 with
      antiperovskite structure.
AB  - We report the magnetic, electrical, and thermoelectric properties of SnCCo3,
      where good thermoelectric performance [figure of merit ZT ~ 0.035(2), 258 K] and
      strong electron correlation (Kadowaki-Woods ratio RKW ~ 4a0) are observed. The
      thermoelectric properties of ACCo3 (A = Al, Ga, Ge) and SnCM3 (M = Mn, Fe) were
      also investigated for comparison. As a result, the ZT value of SnCCo3 is the
      largest among all of those samples, which is mainly attributed to the large
      Seebeck coefficient caused by the strong electron correlation and low carrier
      density. Moreover, the ZT value can be effectively enhanced by proper chemical
      doping in SnCCo3. 

PMID- 24665907
TI  - Combining auctions and performance-based payments in a forest enrichment field
      trial in Western Kenya.
AB  - Cost-effectiveness is an important aspect in the assessment of payments for
      environmental services (PES) initiatives. In participatory field trials with
      communities in Western Kenya, we combined procurement auctions for forest
      enrichment contracts with performance-based payments and compared the outcomes
      with a baseline scenario currently used by the Kenyan Forest Service. Procurement
      auctions were the most cost-effective. The competitive nature of the auction
      reduced contracting expenses (provision costs), and the result-oriented payments
      provided additional incentives to care for the planted seedlings, resulting in
      their improved survival rates (service quantity). These gains clearly exceeded
      increases in transaction costs associated with conducting an auction. The number
      of income-poor auction participants and winners was disproportionately high and
      local institutional buy-in was remarkably strong. Our participatory approach may,
      however, require adaptations when conducted at a larger scale. Although the
      number of contracts we monitored was limited and prohibited the use of
      statistical tests, our study is one of the first to reveal the benefits of using
      auctions for PES in developing countries.

PMID- 24665908
TI  - Do subjects with aggressive and chronic periodontitis exhibit a different
      cytokine/chemokine profile in the gingival crevicular fluid? A systematic review.
AB  - BACKGROUND AND OBJECTIVE: Microbiological and immunological hypotheses have been
      raised to explain the differences in the clinical manifestations of aggressive
      periodontitis and chronic periodontitis. However, studies comparing the
      cytokine/chemokine profiles in gingival crevicular fluid between these two
      clinical conditions have so far not been compiled. This systematic review aimed
      to answer the following question: "Do subjects with aggressive periodontitis and
      chronic periodontitis have a different profile of cytokines/chemokines in the
      gingival crevicular fluid?" MATERIAL AND METHODS: An electronic database search
      of MEDLINE/PubMed and Embase was performed from 1990 up to and including August
      2013, using MeSH terms and other keywords. Titles and abstracts were screened and
      the papers that satisfied eligibility criteria were assessed. RESULTS: Of 1954
      titles, 17 studies reporting the levels of 21 different cytokines/chemokines were
      included. Most studies did not find any significant differences in the gingival
      crevicular fluid levels of cytokines/chemokines between aggressive periodontitis
      and chronic periodontitis. Some studies demonstrated that the levels of specific
      proinflammatory and anti-inflammatory cytokines/chemokines were higher (n = 5)
      and lower (n = 3), respectively, in aggressive periodontitis than in chronic
      periodontitis. The studies differed in the manner in which they reported the
      results (e.g. concentrations or total amounts). It was not clear in some studies
      whether the sample sites from both groups were matched for disease severity. Some
      studies did not take into account confounders, such as smoking. CONCLUSION: The
      current weight of evidence is not sufficient to prove that there are distinct
      gingival crevicular fluid cytokine/chemokine profiles for patients with
      aggressive periodontitis and chronic periodontitis.

PMID- 24665910
TI  - Effect of treatment with methotrexate and coal tar on adipokine levels and
      indices of insulin resistance and sensitivity in patients with psoriasis
      vulgaris.
AB  - BACKGROUND AND OBJECTIVES: Recent studies have implicated adipokines in the
      pathogenesis of the immune-mediated inflammatory disease, psoriasis and its
      associated comorbidities. Hence, we undertook to study adipokine levels and
      indices of insulin resistance and sensitivity in patients with psoriasis
      vulgaris, in comparison with controls and their association with disease severity
      and response to therapy. METHODS: Sixty cases of psoriasis vulgaris and 60 age-
      and gender-matched healthy controls were included in this study. Severity grading
      according to psoriasis area severity index scoring was done in all psoriatics.
      Serum levels of adipokines [leptin, adiponectin, resistin and interleukin-6 (IL
      6)] and insulin were estimated in all psoriatics at baseline and at 12 weeks on
      follow-up and in controls. RESULTS: Baseline levels of the inflammatory
      adipokines (leptin, resistin and IL-6) and insulin resistance indices were
      significantly higher in psoriatics, as compared to controls, while that of the
      anti-inflammatory adipokine, adiponectin and insulin sensitivity indices were
      significantly lower in psoriatics, as compared with controls. Baseline
      inflammatory adipokines, serum insulin level and insulin resistance indices
      demonstrated a significant positive correlation with the severity of psoriasis,
      while the anti-inflammatory adipokine, adiponectin and insulin sensitivity
      indices demonstrated a significant negative correlation with the disease
      severity. After 12 weeks of therapy (both topical and systemic), there was a
      significant reduction in the levels of inflammatory adipokines and a significant
      increase in the levels of anti-inflammatory adipokine-adiponectin. However, a
      significant decrease in insulin levels and insulin resistance indices were
      observed only with systemic therapy with methotrexate. CONCLUSION: The present
      results implicate that adipokines are significantly associated with pathogenesis
      of psoriasis and hence adequate and early control of psoriasis may contribute to
      the decreased development of metabolic syndrome, including the risk of
      cardiovascular disease.

PMID- 24665911
TI  - Role of RASSF1A promoter methylation in the pathogenesis of ovarian cancer: a
      meta-analysis.
AB  - OBJECTIVE: The aim of the current meta-analysis was to comprehensively assess the
      role of RASSF1A promoter methylation in the pathogenesis of ovarian cancer.
      METHOD: A range of electronic databases were searched: Web of Science (1945
      2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966-2013), EMBASE
      (1980-2013), CINAHL (1982-2013), and the Chinese Biomedical Database (1982-2013)
      without language restrictions. Meta-analysis was conducted using the STATA 12.0
      software. The crude odds ratio (OR) with its corresponding 95% confidence
      interval (CI) was calculated. RESULTS: Twelve clinical cohort studies with a
      total of 739 ovarian cancer patients were included in the current meta-analysis.
      The results of our meta-analysis suggested that the frequency of RASSF1A promoter
      methylation in cancer tissues was higher compared with benign, adjacent, and
      normal tissues (cancer tissues vs. benign tissues: OR=9.92, 95% CI: 7.67-12.82,
      p<0.001; cancer tissues vs. adjacent tissues: OR=68.15, 95% CI: 39.30-118.18,
      p<0.001; cancer tissues vs. normal tissues: OR=30.71, 95% CI: 23.12-40.80,
      p<0.001; respectively). Subgroup analysis based on ethnicity and sample types
      revealed that RASSF1A gene methylation was closely associated with the
      pathogenesis of ovarian cancer in all subgroups (all p<0.05). CONCLUSION: Our
      findings indicated that abnormal RASSF1A promoter methylation may be strongly
      correlated with the pathogenesis of ovarian cancer.

PMID- 24665912
TI  - Park Play: a picture description task for assessing childhood motor speech
      disorders.
AB  - The purpose of this study was to develop a picture description task for eliciting
      connected speech from children with motor speech disorders. The Park Play scene
      is a child-friendly picture description task aimed at augmenting current
      assessment protocols for childhood motor speech disorders. The design process
      included a literature review to: (1) establish optimal design features for child
      assessment, (2) identify a set of evidence-based speech targets specifically
      tailored to tax the motor speech system, and (3) enhance current assessment
      tools. To establish proof of concept, five children (ages 4;3-11;1) with
      dysarthria or childhood apraxia of speech were audio-recorded while describing
      the Park Play scene. Feedback from the feasibility test informed iterative design
      modifications. Descriptive, segmental, and prosodic analyses revealed the task
      was effective in eliciting desired targets in a connected speech sample, thereby
      yielding additional information beyond the syllables, words, and sentences
      generally elicited through imitation during the traditional motor speech
      examination. Further discussion includes approaches to adapt the task for a
      variety of clinical needs.

PMID- 24665913
TI  - Creating communicatively accessible healthcare environments: perceptions of
      speech-language pathologists.
AB  - There is a growing body of research that indicates that a person with a
      communication disability communicates and participates more effectively given a
      communicatively accessible environment. If this research is to be translated into
      practice then one needs to determine who will take on the role of creating
      communicatively accessible environments. This research adopted a qualitative
      methodology to explore the perceptions of speech-language pathologists about
      working to create communicatively accessible healthcare settings. Fifteen speech
      language pathologists in three focus groups participated in this research. The
      focus group discussions were transcribed and analysed thematically. Thematic
      analysis indicated that speech-language pathologists believe there are four main
      benefits in creating communicatively accessible healthcare environments. These
      are Benefits for all people: Access for all, Benefits for healthcare
      administrators, Benefits for those wanting to improve communication with
      patients, and Benefits to the capacity to provide communicatively accessible
      environments. However, they believe these benefits can only be achieved if; The
      communication resources are available, Skilled, knowledgeable and supportive
      healthcare providers are available; and Systems are in place to support a whole
      of-hospital approach. This research supports the development of a new role to
      improve the communicative accessibility of healthcare settings.

PMID- 24665915
TI  - Multispecies spawning sites for fishes on a low-latitude coral reef: spatial and
      temporal patterns.
AB  - Spawning sites used by one or more species were located by intensively searching
      nearshore coral reefs of Kimbe Bay (New Britain, Papua New Guinea). Once
      identified, the spawning sites were surveyed repeatedly within fixed 5 m radius
      circular areas, for  > 2000 h of observations ranging from before dawn to after
      dusk spanning 190 days between July 2001 and May 2004. A total of 38 spawning
      sites were identified on the seven study reefs distributed at an average of one
      site every 60 m of reef edge. Pelagic spawning was observed in 41 fish species
      from six families. On three intensively studied reefs, all 17 spawning sites
      identified were used by at least three species, with a maximum of 30 different
      species observed spawning at a single site. Spawning was observed during every
      month of the study, on all days of the lunar month, at all states of the tide and
      at most hours of the day studied. Nevertheless, the majority of species were
      observed spawning on proportionately more days from December to April, on more
      days around the new moon and in association with higher tides. The strongest
      temporal association, however, was with species-specific diel spawning times
      spanning < 3 h for most species. While dawn spawning, afternoon spawning and dusk
      spawning species were differentiated, the time of spawning for the striated
      surgeonfish Ctenochaetus striatus also differed significantly among sites. The
      large number of species spawning at the same restricted locations during
      predictable times suggests that these sites are extremely important on this low
      latitude coral reef. 

PMID- 24665917
TI  - A meta-analysis of association of vitamin D receptor BsmI gene polymorphism with
      the risk of type 1 diabetes mellitus.
AB  - Association between vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism
      and the risk of type 1 diabetes mellitus (T1DM) from the published reports are
      still conflicting. This study was conducted to evaluate the relationship between
      VDR BsmI gene polymorphism and the risk of T1DM using meta-analysis method. The
      association studies were identified from PubMed, and Cochrane Library on 1
      December 2013, and eligible investigations were included and synthesized using
      meta-analysis method. Twenty-three reports were recruited into this meta-analysis
      for the association of VDR BsmI gene polymorphism with T1DM susceptibility. In
      overall populations, bb genotype was associated with T1DM, but the B allele and
      BB genotype were not. In Asians and Latino population, B allele and bb genotype
      were associated with TIDM risk, but BB genotype was not. In Caucasians, VDR BsmI
      gene polymorphism was not associated with the T1DM risk. In Africans, B allele
      and BB genotype were associated with T1DM risk, but the bb genotype was not.
      However, the sample size for Latino population and Africans was small. In
      conclusion, VDR BsmI B allele, bb genotype was associated with T1DM risk in
      Asians, and bb genotype was associated with T1DM risk in overall populations.
      However, more studies should be conducted to confirm it.

PMID- 24665909
TI  - Recent advances on the delta opioid receptor: from trafficking to function.
AB  - Within the opioid family of receptors, delta (DOPrs) and MU opioid receptors
      (MOPrs) are typical GPCRs that activate canonical second-messenger signalling
      cascades to influence diverse cellular functions in neuronal and non-neuronal
      cell types. These receptors activate well-known pathways to influence ion channel
      function and pathways such as the map kinase cascade, AC and PI3K. In addition
      new information regarding opioid receptor-interacting proteins, downstream
      signalling pathways and resultant functional effects has recently come to light.
      In this review, we will examine these novel findings focusing on the DOPr and, in
      doing so, will contrast and compare DOPrs with MOPrs in terms of differences and
      similarities in function, signalling pathways, distribution and interactions. We
      will also discuss and clarify issues that have recently surfaced regarding the
      expression and function of DOPrs in different cell types and analgesia. LINKED
      ARTICLES: This article is part of a themed section on Opioids: New Pathways to
      Functional Selectivity. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24665916
TI  - Methodology for establishing a population-based birth cohort focusing on couple
      fertility and children's development, the Upstate KIDS Study.
AB  - BACKGROUND: Critical data gaps remain regarding infertility treatment and child
      development. We assessed the utility of a birth certificate registry for
      developing a population cohort aimed at answering such questions. METHODS: We
      utilised the Upstate New York livebirth registry (n = 201,063) to select births
      conceived with (n = 4024) infertility treatment or exposed infants, who were then
      frequency-matched by residence to a random sample of infants conceived without (n
      = 14,455) treatment or unexposed infants, 2008-10. Mothers were recruited at 2-4
      months postpartum and queried about their reproductive histories, including
      infertility treatment for comparison with birth certificate data. Overall, 1297
      (32%) mothers of exposed and 3692 of unexposed (26%) infants enrolled. RESULTS:
      Twins represented 22% of each infant group. The percentage of infants conceived
      with/without infertility treatment was similar whether derived from the birth
      registry or maternal report: 71% none, 16% drugs or intrauterine insemination,
      and 14% assisted reproductive technologies (ART). Concordant reporting between
      the two data sources was 93% for no treatment, 88% for ART, and 83% for fertility
      drugs, but differed by plurality. Exposed infants had slightly (P < 0.01) earlier
      gestations than unexposed infants (38.3 +/- 2.8 and 38.7 +/- 2.7 weeks,
      respectively) based upon birth certificates but not maternal report (38.7 +/- 2.7
      and 38.7 +/- 2.9, respectively). Conversely, mean birthweight was comparable
      using birth certificates (3157 +/- 704 and 3194 +/- 679 g, respectively), but
      differed using maternal report (3167 +/- 692 and 3224 +/- 661, respectively P <
      0.05). CONCLUSIONS: The birth certificate registry is a suitable sampling
      framework as measured by concordance with maternally reported infertility
      treatment. Future efforts should address the impact of factors associated with
      discordant reporting on research findings.

PMID- 24665918
TI  - Spreading the concept: an attempt to translate an interprofessional clinical
      placement across a Danish hospital.
AB  - In a Danish Interprofessional Training Unit (ITU), the clinical tutors have
      succeeded in developing a safe learning environment combined with challenging the
      students by giving them responsibility for the patient's care and rehabilitation.
      In the ITU, students improved their uniprofessional and interprofessional
      knowledge and capability while strengthening their professional identity. It was,
      therefore, decided to make an attempt to transfer these interprofessional
      learning and teaching methods to another setting. The aims of this study were to
      evaluate whether the students learned about interprofessional collaboration and
      strengthened their professional identity and whether the clinical tutors could
      create a safe and challenging learning environment. Clinical tutors from the
      professions occupational therapy, physiotherapy, and nursing together planned the
      pedagogical approach and practical organization of two pilot studies in an
      orthopedic ward. After the intervention, focus group interviews of students and
      clinical tutors were performed and analyzed. The findings indicated that a one
      week interprofessional clinical placement can contribute to students learning
      about interprofessional collaboration and to their development of professional
      identity. The data from the clinical tutors indicated that they needed to create
      a safe and challenging learning environment but emphasized that a thorough
      planning and continuous monitoring and adjusting of the clinical placement is
      necessary for success. The study documents that it is possible to create
      successful interprofessional learning opportunities in a normal ward environment
      in a restricted time frame. This knowledge can be applied to other ward settings
      where interprofessional clinical training is a natural possibility.

PMID- 24665920
TI  - Symptomatic and asymptomatic long-term recurrences following transcatheter atrial
      fibrillation ablation.
AB  - BACKGROUND: Atrial fibrillation (AF) relapses, following transcatheter AF
      ablation, are frequently reported based on patients' symptoms, scheduled
      electrocardiograms (ECGs), or 24-hour Holter recordings. The aim of this study is
      to determine the incidence of asymptomatic and symptomatic AF recurrences, using
      continuous subcutaneous ECG monitoring, in the long-term follow-up of patients
      with paroxysmal or persistent AF undergoing transcatheter ablation. METHODS AND
      RESULTS: In total 113 consecutive patients symptomatic for paroxysmal or
      persistent AF were enrolled. All patients underwent pulmonary vein isolation plus
      left linear lesions. The insertable cardiac monitor (ICM), subcutaneously
      implanted during the ablation procedure, recorded the amount of AF per day (daily
      burden) and per last follow-up period (total AF burden). Based on symptoms and on
      scheduled 12-lead ECG performed during follow-up, 40 patients (35.4%) suffered AF
      recurrences. By means of ICM data, however, arrhythmia relapses were recorded
      within 75 patients (66.3%), of whom 35 (46.7%) were asymptomatic. Patients
      suffering symptomatic AF recurrences resulted, at univariate analysis, older
      (66.6 +/- 8.4 years vs 61.6 +/- 10.7 years) and suffering greater AF burden (88.8
      +/- 26.9% vs 8.0 +/- 8.0%). CONCLUSIONS: AF ablation outcome based on patients'
      symptoms and/or scheduled ECGs underestimated relapses, as up to half of the
      patients, during a long-term follow-up, suffer asymptomatic recurrences.

PMID- 24665919
TI  - Microbiological assessment of the implant-abutment interface in different
      connections: cross-sectional study after 5 years of functional loading.
AB  - OBJECTIVE: To evaluate the bacterial microflora present inside the implant
      connection and in the peri-implant sulcus fluid of healthy implants, and to
      analyze the relationships between these harboring sites for four different
      implant systems after at least 5 years of functional loading. MATERIALS AND
      METHODS: A cross-sectional study was performed involving 40 patients treated with
      metal-ceramic cemented bridges supported by at least two healthy implants
      functionally loaded for 5 years. Four different implant-abutment connections were
      studied: external hexagon (control group), double internal hexagon (test group
      1), internal hexagon with external collar (test group 2), and conical connection
      (test group 3). Samples for microbiological analysis were obtained from three
      types of sites: peri-implant sulci, connections' inside and abutments surface
      and, as control, gingival sulci of neighboring teeth. Quantitative real-time PCR
      was carried out for Total Bacterial Count and for 10 microorganisms:
      Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella
      forsythensis, Treponema denticola, Prevotella intermedia, Peptostreptococcus
      micros, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens, and
      Candida albicans. The response variables were percentage of positive sites and
      absolute bacterial load. The relations of the response variables with the type of
      connection and of sampling site were assessed using generalized estimating
      equations. RESULTS: Regarding the analysis of positivity to bacteria in the peri
      implant sulcus no significant differences were observed. Analyzing the
      connection's inside, none of the connection designs had the capacity to prevent
      microbiological leakage through the implant/abutment microgap. Test group 3
      presented the lowest mean values for red complex bacteria and control group the
      highest, although differences were non-significant. Statistical significance was
      only reached for Treponema denticola in the bacterial load analysis inside the
      connection. Test groups 1 and 2 yielded lower values for orange complex bacteria
      but only for Peptostreptococos micros the differences resulted significant. Test
      groups 2 and 3 had significantly lower total bacterial counts in the peri-implant
      sulcus and inside the connection. CONCLUSIONS: Outcomes suggested that all the
      analyzed connections resulted contaminated after 5 years of functional loading.
      However, the connection design might influence bacterial activity levels
      qualitatively and quantitatively, especially inside the implant connection.

PMID- 24665921
TI  - Theoretical investigation of bacteria polarizability under direct current
      electric fields.
AB  - We present a theoretical model to investigate the influence of soft
      polyelectrolyte layers on bacteria polarizability. We resolve soft-layer
      electrokinetics by considering the pH-dependent dissociation of ionogenic groups
      and specific interactions of ionogenic groups with the bulk electrolyte to go
      beyond approximating soft-layer electrokinetics as surface conduction. We model
      the electrokinetics around a soft particle by modified Poisson-Nernst-Planck
      equations (PNP) to account for the effects of ion transport in the soft layer and
      electric double layer. Fluid flow is modeled by modified Stokes equations
      accounting for soft-layer permeability. Two test cases are presented to
      demonstrate our model: fibrillated and unfibrillated Streptococcus salivarius
      bacteria. We show that electrolytic and pH conditions significantly influence the
      extent of soft-particle polarizability in dc fields. Comparison with an
      approximate analytical model based on Dukhin-Shilov theory for soft particles
      shows the importance of resolving soft-layer electrokinetics. Insights from this
      study can be useful in understanding the parameters that influence soft-particle
      dielectrophoresis in lab-on-a-chip devices. 

PMID- 24665923
TI  - Synthesis and comparative photoswitching studies of unsymmetrical 2,3
      diarylcyclopent-2-en-1-ones.
AB  - Photochromic diarylethenes (DAEs) based on the unsymmetrical ethene "bridge"
      bearing heterocycles of the different nature (oxazole and thiophene) as aromatic
      moieties have been designed and the photoswitching properties have been studied.
      The comparative studies of the photochromic characteristics of unsymmetrical
      isomeric 2,3-diarylcyclopent-2-en-1-ones have shown that the isomers have
      different thermal stability, absorption maxima, and quantum yields. It was found
      that the unsymmetrical diarylcyclopentenone bearing at second position of the
      cyclopentenone ring the thiophene unit displays high thermally stability,
      hypsochromic shift of absorption maxima wavelengths of initial and cyclic forms,
      and high quantum yields of cyclization and cycloreversion reactions. The
      replacement of the carbonyl group with oxime leads to a reduction of the
      difference in the photochromic properties of these isomers and just as the
      reduction of the carbonyl group to the hydroxy-group negates this difference to
      zero. The intramolecular hydrogen bond formation in the oxime and hydroxy
      derivatives was confirmed by IR and (1)H NMR spectral analysis, but the increase
      of the quantum yields of the cyclization reaction in a nonpolar hexane is
      observed only in the case of hydroxy derivatives that can be explained by the
      formation of more rigid six-membered heterocycle in hydrogen bonding.

PMID- 24665922
TI  - Genetic disorders of thyroid metabolism and brain development.
AB  - Normal thyroid metabolism is essential for human development, including the
      formation and functioning of the central and peripheral nervous system. Disorders
      of thyroid metabolism are increasingly recognized within the spectrum of
      paediatric neurological disorders. Both hypothyroid and hyperthyroid disease
      states (resulting from genetic and acquired aetiologies) can lead to
      characteristic neurological syndromes, with cognitive delay, extrapyramidal
      movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations.
      In this review, the neurological manifestations of genetic disorders of thyroid
      metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome
      and benign hereditary chorea. We report in detail the clinical features, major
      neurological and neuropsychiatric manifestations, molecular genetic findings,
      disease mechanisms, and therapeutic strategies for these emerging genetic 'brain
      thyroid' disorders. 

PMID- 24665924
TI  - Short- to intermediate-term follow-up in patients treated with the combination of
      311-nm ultraviolet B phototherapy and biological agents.

PMID- 24665925
TI  - Enthalpy/entropy compensation effects from cavity desolvation underpin broad
      ligand binding selectivity for rat odorant binding protein 3.
AB  - Evolution has produced proteins with exquisite ligand binding specificity, and
      manipulating this effect has been the basis for much of modern rational drug
      design. However, there are general classes of proteins with broader ligand
      selectivity linked to function, the origin of which is poorly understood. The
      odorant binding proteins (OBPs) sequester volatile molecules for transportation
      to the olfactory receptors. Rat OBP3, which we characterize by X-ray
      crystallography and NMR, binds a homologous series of aliphatic gamma-lactones
      within its aromatic-rich hydrophobic pocket with remarkably little variation in
      affinity but extensive enthalpy/entropy compensation effects. We show that the
      binding energetics are modulated by two desolvation processes with quite
      different thermodynamic signatures. Ligand desolvation follows the classical
      hydrophobic effect; however, cavity desolvation is consistent with the liberation
      of "high energy" water molecules back into bulk solvent with a strong, but
      compensated, enthalpic contribution, which together underpin the origins of broad
      ligand binding selectivity. 

PMID- 24665926
TI  - Definition and treatment of resistance to tyrosine kinase inhibitors in chronic
      myeloid leukemia.
AB  - Resistance to tyrosine kinase inhibitors (TKIs) has many facets. The causes of
      resistance include low patient compliance, low plasma or intracellular drug
      concentration, BCR-ABL1 mutations, and clonal chromosome abnormalities in Ph+
      cells, but in at least 50% of patients the causes are currently unknown. Primary
      resistance occurs when a predefined response level is not achieved within a
      prespecified period of time. Not achieving a complete hematologic response (CHR)
      within 3 months, not achieving a partial cytogenetic response and/or a BCR-ABL1
      transcripts level <=10% (international standard) within 6 months, and not
      achieving a complete cytogenetic response (CCyR) and/or a BCR-ABL1 transcripts
      level <1% within 12 months, define primary resistance. Secondary resistance is
      defined by a loss of CHR, or CCyR, or major molecular response. Resistance to
      imatinib calls without exceptions for a second-generation TKI. In case of
      resistance to two TKIs, an allogeneic stem cell transplantation should be
      considered. 

PMID- 24665927
TI  - Predicting extinction risk of Brazilian Atlantic forest angiosperms.
AB  - Understanding how plant life history affects species vulnerability to
      anthropogenic disturbances and environmental change is a major ecological
      challenge. We examined how vegetation type, growth form, and geographic range
      size relate to extinction risk throughout the Brazilian Atlantic Forest domain.
      We used a database containing species-level information of 6,929 angiosperms
      within 112 families and a molecular-based working phylogeny. We used decision
      trees, standard regression, and phylogenetic regression to explore the
      relationships between species attributes and extinction risk. We found a
      significant phylogenetic signal in extinction risk. Vegetation type, growth form,
      and geographic range size were related to species extinction risk, but the effect
      of growth form was not evident after phylogeny was controlled for. Species
      restricted to either rocky outcrops or scrub vegetation on sandy coastal plains
      exhibited the highest extinction risk among vegetation types, a finding that
      supports the hypothesis that species adapted to resource-limited environments are
      more vulnerable to extinction. Among growth forms, epiphytes were associated with
      the highest extinction risk in non-phylogenetic regression models, followed by
      trees, whereas shrubs and climbers were associated with lower extinction risk.
      However, the higher extinction risk of epiphytes was not significant after
      correcting for phylogenetic relatedness. Our findings provide new indicators of
      extinction risk and insights into the mechanisms governing plant vulnerability to
      extinction in a highly diverse flora where human disturbances are both frequent
      and widespread.

PMID- 24665928
TI  - A physiological framework to explain genetic and environmental regulation of
      tillering in sorghum.
AB  - Tillering determines the plant size of sorghum (Sorghum bicolor) and an
      understanding of its regulation is important to match genotypes to prevalent
      growing conditions in target production environments. The aim of this study was
      to determine the physiological and environmental regulation of variability in
      tillering among sorghum genotypes, and to develop a framework for this
      regulation. Diverse sorghum genotypes were grown in three experiments with
      contrasting temperature, radiation and plant density to create variation in
      tillering. Data on phenology, tillering, and leaf and plant size were collected.
      A carbohydrate supply/demand (S/D) index that incorporated environmental and
      genotypic parameters was developed to represent the effects of assimilate
      availability on tillering. Genotypic differences in tillering not explained by
      this index were defined as propensity to tiller (PTT) and probably represented
      hormonal effects. Genotypic variation in tillering was associated with
      differences in leaf width, stem diameter and PTT. The S/D index captured most of
      the environmental effects on tillering and PTT most of the genotypic effects. A
      framework that captures genetic and environmental regulation of tillering through
      assimilate availability and PTT was developed, and provides a basis for the
      development of a model that connects genetic control of tillering to its
      phenotypic consequences. 

PMID- 24665929
TI  - Androgenetic alopecia and polymorphism of the androgen receptor gene (SNP rs6152)
      in patients with benign prostate hyperplasia or prostate cancer.
AB  - BACKGROUND: Both androgenetic alopecia (AGA) and carcinoma of the prostate (CaP)
      or benign prostatic hyperplasia (BPH) are androgen-dependent disorders.
      OBJECTIVE: To investigate the relationships between male androgenetic alopecia,
      androgen receptor (AR) gene polymorphism (SNP rs6152) and clinical
      characteristics of BPH and prostate cancer. METHODS: Overall, 309 male subjects
      with prostate disease (BPH or CaP) were examined. We evaluated the standard
      grades of AGA (I-VII) by Hamilton-Norwood classification and 195 patients were
      also assessed by phototrichogram. Prostate-specific antigen (PSA) and
      testosterone levels were also measured. Polymorphism rs6152 of the AR was
      evaluated from blood samples by PCR-RFLP. Data were statistically evaluated.
      RESULTS: The expected positive correlation between age and AGA grade and the
      expected negative correlation between hair density and age and between
      anagen/telogen and AGA were found. A statistically significant difference between
      patients with A and G alleles in terms of AGA grade was found. The predominant G
      allele was more frequent in patients with higher grade of alopecia and in
      patients with significantly higher PSA. There was no correlation between
      diagnosis (BPH or CaP) and polymorphism. Patients with prostate inflammation had
      a statistically significant higher grade of AGA, together with higher PSA.
      CONCLUSIONS: We confirmed that the AR gene polymorphism (SNP rs6152 G>A) is
      associated with the development of AGA and higher PSA levels in patients with BPH
      but not cancer. A novel finding of our study is that BPH patients with prostate
      inflammation had a significantly higher grade of AGA together with significantly
      higher PSA levels.

PMID- 24665930
TI  - Recombinant activin A enhances the growth and survival of isolated preantral
      follicles cultured three-dimensionally in extracellular basement matrix protein
      (matrigel) under serum-free conditions.
AB  - Development of in vitro technologies that will allow the culture of early stage
      follicles before antral stage is an essential part of research in reproductive
      biology in order to understand the ovarian folliculogenesis better. Current
      evidence suggests that oocyte and somatic cells-derived growth factors
      interacting with each other and extracellular matrix proteins at paracrine level
      are involved in this early, gonadotrophin-independent phase of follicle growth.
      Basement membrane matrix protein (MatrigelTM) is a soluble gel rich in
      extracellular matrix proteins and growth factors. Activin A promotes preantral
      follicle growth in vivo by inducing the proliferation of granulosa cells and by
      upregulating the expression of FSH receptor and aromatase enzyme. We hypothesized
      that activin A and matrigel may provide a better in vitro environment for early
      stage preantral follicles. Preantral follicles isolated from 14-21 day old BALB/c
      mice were cultured in matrigel +/- activin A for four days. The growth (119.4%
      versus 45.4%, p < 0.05; respectively) and survival rates (76.3% versus 43.7%, p <
      0.05; respectively) of the follicles treated with activin A were significantly
      higher compared to those without activin A. These results suggest that Activin A
      and matrigel provide a better in vitro milieu for the growth of isolated ovarian
      follicles.

PMID- 24665931
TI  - KSbB2O6 and BaSb2B4O12: novel boroantimonates with 3D anionic architectures
      composed of 1D chains of SbO6 octahedra and B2O5 groups.
AB  - Two new boroantimonates, namely, KSbB2O6 and BaSb2B4O12, have been successfully
      synthesized through high-temperature solid state reactions. Their structures
      feature two types of novel anionic 3D frameworks composed of 1D chains of corner
      sharing SbO6 octahedra that are interconnected by B2O5 groups. The 1D chains of
      corner-sharing SbO6 octahedra in polar KSbB2O6 (space group Cc) are extended
      along the c-axis, whereas those in the centrosymmetric BaSb2B4O12 (space group
      C2/c) are propagated along the [101] direction. The K(+) ions are located at the
      1D tunnels of the anionic frameworks along both b- and c-axis, whereas Ba(2+)
      ions are located at the 1D tunnels of the anionic frameworks along both the a-
      and c-axis. KSbB2O6 is a polar material that displays weak SHG response, whereas
      BaSb2B4O12 is centrosymmetric and not SHG active. Studies on their optical
      properties, thermal stability, and band structure calculations based on DFT
      methods have been also performed. 

PMID- 24665932
TI  - Carotenoids, but not vitamin A, improve iron uptake and ferritin synthesis by
      Caco-2 cells from ferrous fumarate and NaFe-EDTA.
AB  - Due to the high prevalence of iron and vitamin A deficiencies and to the
      controversy about the role of vitamin A and carotenoids in iron absorption, the
      objectives of this study were to evaluate the following: (1) the effect of a
      molar excess of vitamin A as well as the role of tannic acid on iron uptake by
      Caco-2 cells; (2) iron uptake and ferritin synthesis in presence of carotenoids
      without pro-vitamin A activity: lycopene, lutein, and zeaxantin; and (3) iron
      uptake and ferritin synthesis from ferrous fumarate and NaFe-EDTA. Cells were
      incubated 1 h at 37  degrees C in PBS pH 5.5, containing (59) Fe and different
      iron compounds. Vitamin A, ferrous fumarate, beta-carotene, lycopene, lutein,
      zeaxantin, and tannic acid were added to evaluate uptake. Ferritin synthesis was
      measured 24 h after uptake experiments. Vitamin A had no effect on iron uptake by
      Caco-2 cells, and was significantly lower from NaFe-EDTA than from ferrous
      fumarate (15.2 +/- 2.5 compared with 52.5 +/- 8.3 pmol Fe/mg cell protein,
      respectively). Carotenoids increase uptake up to 50% from fumarate and up to 300%
      from NaFe-EDTA, since absorption from this compound is low when administered
      alone. We conclude the following: (1) There was no effect of vitamin A on iron
      uptake and ferritin synthesis by Caco-2cells. (2) Carotenoids significantly
      increased iron uptake from ferrous fumarate and NaFe-EDTA, and were capable of
      partially overcoming the inhibition produced by tannic acid. (3) Iron uptake by
      Caco-2 cell from NaFe-EDTA was significantly lower compared to other iron
      compounds, although carotenoids increased and tannic acid inhibited iron uptake
      comparably to ferrous fumarate. 

PMID- 24665933
TI  - Structure-property correlation in EEMAO fabricated TiO2-Al2O3 nanocomposite
      coatings.
AB  - We grew TiO2-Al2O3 nanocomposite coatings on titanium substrates by
      electrophoretic enhanced microarc oxidation (EEMAO) technique under several
      voltages and established a correlation between microstructure, surface hardness,
      and corrosion resistance of the coatings in sulfuric acid and sodium chloride
      solutions. Structural analysis revealed that the coatings contained anatase,
      rutile, alumina, and tialite phases. Formation kinetics of tialite phase was
      studied. It was found that increasing the voltage gives rise to a coarser
      morphology, i.e., larger pore size, and incorporation of more alumina
      nanoparticles into the layers. It is shown that surface hardness of the titanium
      substrates increased by a factor of 4 following EEMAO treatment. Corrosion
      resistance of titanium was enhanced significantly. Resistance against pitting
      corrosion was improved as well. We proposed a formation mechanism for the TiO2
      Al2O3 composite coatings at different voltages based on the chemical and
      electrochemical foundations. 

PMID- 24665934
TI  - Non-preferential fuelling of the Na(+)/K(+)-ATPase pump.
AB  - There is abundant evidence that glycolysis and the Na(+)/K(+)-ATPase pump are
      functionally coupled, and it is thought that the nature of the coupling is
      energetic, with glycolysis providing the ATP that fuels the pump. This notion has
      been instrumental to current models of brain energy metabolism. However,
      structural and biophysical considerations suggest that the pump should also have
      access to mitochondrial ATP, which is much more abundant. In the present study,
      we have investigated the source of ATP that fuels the Na(+) pump in astrocytes,
      taking advantage of the high temporal resolution of recently available FRET
      nanosensors for glucose, lactate and ATP. The activity of the Na(+) pump was
      assessed in parallel with the Na(+)-sensitive dye SBFI AM (Na(+)-binding
      benzofuran isophthalate acetoxymethyl ester). OXPHOS (oxidative phosphorylation)
      inhibition resulted in bulk ATP depletion and a 5-fold stimulation of glycolytic
      flux, in spite of which Na(+) pumping was inhibited by 90%. Mathematical
      modelling of ATP dynamics showed that the observed pump failure is inconsistent
      with preferential fuelling of the Na(+) pump by glycolytic ATP. We conclude that
      the nature of the functional coupling between the Na(+) pump and the glycolytic
      machinery is not energetic and that the pump is mainly fuelled by mitochondrial
      ATP.

PMID- 24665935
TI  - Novel use for polyvinylpyrrolidone as a macromolecular crowder for enhanced
      extracellular matrix deposition and cell proliferation.
AB  - Macromolecular crowding (MMC) is a biophysical effect that governs biochemical
      processes inside and outside of cells. Since standard cell culture media lack
      this effect, the physiological performance of differentiated and progenitor
      cells, including extracellular matrix (ECM) deposition, is impaired in vitro. To
      bring back physiological crowdedness to in vitro systems, we have previously
      introduced carbohydrate-based macromolecules to culture media and have achieved
      marked improvements with mixed MMC in terms of ECM deposition and differentiation
      of mesenchymal stem cells (MSCs). We show here that although this system is
      successful, it is limited, due to viscosity, to only 33% of the fractional volume
      occupancy (FVO) of full serum, which we calculated to have an FVO of
      approximately 54% v/v. We show here that full-serum FVO can be achieved using
      polyvinylpyrrolidone (PVP) 360 kDa. Under these conditions, ECM deposition in
      human fibroblasts and MSCs is on par, if not stronger than, with original MMC
      protocols using carbohydrates, but with a viscosity that is not significantly
      changed. In addition, we have found that the proliferation rate for bone marrow
      derived MSCs and fibroblasts increases slightly in the presence of PVP360,
      similar to that observed with carbohydrate-based crowders. A palette of MMC
      compounds is now emerging that enables us to tune the crowdedness of culture
      media seamlessly from interstitial fluid (9% FVO), in which the majority of
      tissue cells might be based, to serum environments mimicking intravascular
      conditions. Despite identical FVO's, individual crowder size effects play a role
      and different cell types appear to have preferences in terms of FVO and the
      crowder that this is achieved with. However, in the quest of crowders that we
      have predicted to have a smoother regulatory approval path, PVP is a highly
      interesting compound, as it has been widely used in the medical and food
      industries and shows a novel promising use in cell culture and tissue
      engineering. 

PMID- 24665936
TI  - A review of the chemistry and uses of crocins and crocetin, the carotenoid
      natural dyes in saffron, with particular emphasis on applications as colorants
      including their use as biological stains.
AB  - The perennial flowering plant, saffron crocus (Crocus sativus L.), is the source
      of the most expensive spice in the world. The dried stigmas of saffron flowers
      are the source of a natural dye, saffron, which has been used from ancient times
      for dyeing silk and fabric rugs, and for painting; it also has been used for
      cooking and in medicine. The yellow compounds present in the dye include crocins,
      which are 20-carbon water soluble glycosyl derivatives of the carotenoid,
      crocetin, and the dicarboxylic acid itself. We review the chemistry of these
      compounds and discuss various applications of saffron as a natural dye. We review
      in particular the use of saffron or its constituents in histopathologic
      techniques.

PMID- 24665937
TI  - Effects of high fat diet induced obesity on peripheral nerve regeneration and
      levels of GAP 43 and TGF-beta in rats.
AB  - The increasing frequency of obesity is important because of its accompanying
      related health problems. The effects of obesity on peripheral nerves have not
      been elucidated. We investigated the effects of obesity on sciatic nerve
      regeneration using electrophysiology, stereology, immunohistochemistry,
      histopathology and functional tests. We used control, obese, control injured and
      obese injured groups of rats. Electrophysiological results showed that nerve
      conduction velocity and EMG were same in the experimental groups, but the
      amplitude of the compound action potential of the control group was significantly
      higher than that of the obese group. Examination of the nerves showed that the
      control and obese groups had both larger axon diameters and thicker myelin
      sheaths. The number of myelinated axons was decreased in both of the injured
      groups. Axon diameters and myelin sheath thicknesses of the control injured group
      were significantly greater those of the obese injured group. There were no
      significant differences in functional tests among the groups. Although growth
      associated protein 43 immunostaining in the control injured group was
      significantly greater than that of the obese injured group, no significant
      difference was observed between the control and obese groups. There was no
      significant difference in immunohistochemical staining for transforming growth
      factor beta 3 between the control injured and obese injured groups. Our results
      suggest that obesity may affect peripheral nerve regeneration negatively after
      crush injury.

PMID- 24665938
TI  - Evaluation of palatal mucosal thickness and its association with age and gender.
AB  - The palatal masticatory mucosa is widely used as donor material for periodontal
      plastic surgery. The thickness of graft tissue is important for graft survival.
      We investigated the thickness of palatal mucosa using a bone sounding technique.
      We also examined the relation of age and gender to the thickness of palatal
      mucosa. Fifty healthy subjects were divided into a younger age group of 25
      subjects, 14-21 years old (mean, 19 years); the older age group consisted of 25
      subjects, 30-59 years old (mean, 34.4 years). A bone sounding method using a
      periodontal probe and endodontic spreader no. 60 was used to assess the thickness
      of palatal mucosa at 15 pre-determined sites defined according to the gingival
      margin and palatal lines. Student's 't' test was used to validate differences in
      mucosal thickness between the groups. The mean thickness of palatal masticatory
      mucosa ranged from 2.5 to 3.7 mm. The younger age group had a thinner mucosa than
      the older age group and females had a thinner mucosa than males. The canine and
      premolar areas appeared to be the most appropriate donor sites for grafting
      procedures.

PMID- 24665939
TI  - Accomplishments of the Trustees and laboratory staff of the Biological Stain
      Commission, 2002-2013.
AB  - During the 12 years from 2002 to 2013, the Trustees and laboratory personnel of
      the Biological Stain Commission (BSC) can claim many accomplishments. These
      accomplishments are itemized under 11 categories: continuous publication of the
      official journal, Biotechnic & Histochemistry; production of four special issues
      of Biotechnic & Histochemistry devoted to specific dyes or stains;
      standardization of staining and dye purity; mechanisms of staining and prediction
      of dye behavior; publication of books or book chapters; effects of fixation and
      processing on staining; cancer research; immunohistochemistry; BSC Laboratory
      activities; miscellaneous publications; and administrative accomplishments.

PMID- 24665940
TI  - Phenotypic and molecular characteristics in eleven Chinese patients with 5alpha
      reductase Type 2 deficiency.
AB  - CONTEXT: Steroid 5alpha-reductase type 2 deficiency (5alpha-RD2) is a male
      limited, autosomal recessive inherited disease. Affected 46, XY individuals
      usually present with ambiguous genitalia at birth. An early and precise diagnosis
      is of great value to the long-term prognosis of the disease. OBJECTIVE: To
      describe the clinical features and molecular determinants in 11 Chinese patients
      with the SRD5A2 gene mutation and to investigate the functional alteration
      arising from a novel splicing site mutation identified in one of the patients.
      SUBJECTS AND METHODS: Eleven subjects born with abnormal external genitalia from
      10 unrelated families were recruited. Among them, nine patients who were reared
      as girls underwent virilization and gender change after puberty. Genotyping
      analysis of the SRD5A2 gene was performed in each of the patients. Haplotype
      analysis was performed in five patients with a prevalent mutation of p.G203S to
      illustrate the founder effect in China. Functional impairment of the new variant
      was explored by an in vitro splicing study and enzymatic activity assay. RESULTS:
      Nine mutations in the SRD5A2 gene were detected in the eleven patients. In
      addition to the previously reported p.G203S, p.R227Q, p.N193S, p.R246Q, p.Q6X,
      p.A228V, c.655delT and IVS1-2 A>G, a novel splicing site mutation (IVS4 + 2 T>C)
      was identified. From an in vitro functional study, this mutation was found to
      result in a skipping of exon 4 in the course of mRNA splicing, leading to a
      truncated protein of 205 amino acids that lacks the catalysing activity. Two
      siblings with the same compound heterozygous mutation (IVS1-2A>G/p.G203S)
      exhibited differing phenotypes and opposite patterns of gender rearing. A
      prevalent variation p.V89L combined with c.655delT was revealed to cause a mild
      phenotype of 5alpha-RD2 with a micropenis. CONCLUSION: This cohort study
      describes the phenotypic, biochemical and long-term outcome in 11 Chinese
      patients with 5alpha-RD2 deficiency and defines the genotypic spectrum of SRD5A2
      mutations in China.

PMID- 24665941
TI  - Brugada ECG pattern obscured by right bundle branch block: how to resolve the
      enigma?

PMID- 24665942
TI  - Corrigendum.

PMID- 24665943
TI  - Shedding new light on the role of the sunshine vitamin D for skin health: the
      lncRNA-skin cancer connection.
AB  - Throughout evolution, vertebrates including humans have depended on the sunshine
      vitamin D for their calcified skeletons. As our hunter gatherer forefathers
      ventured from the equator, their skin tone became much lighter in order to permit
      an adequate amount of ultraviolet B radiation to enter the skin to produce the
      vitally important vitamin D. Although sensible sun exposure does not
      significantly increase risk of skin cancer, it has remained a mystery as to why.
      Jiang and Bikle in their viewpoint provide a novel insight as to how Mother
      Nature was able to balance the need for receiving adequate sun exposure to
      produce vitamin D while limiting damage caused by the DNA absorbing the
      ultraviolet B radiation. Long non-coding RNAs which are plentiful in cells have a
      dual personality. Some enhance malignancy, while others act as tumor suppressors.
      Jiang and Bikle provide compelling evidence that these long non-coding RNAs in
      skin cells are responsive to 1,25-dihydroxyvitamin D3 by decreasing their
      carcinogenic activity while enhancing their tumor suppression function presumably
      as a strategy for reducing ultraviolet-induced non-melanoma skin cancer. Mother
      Nature got it right. Sensible sun exposure is important for maintaining an
      adequate vitamin D status. Once formed in the skin, vitamin D can exit into the
      circulation to carry out its physiologic functions on calcium and bone
      metabolism. Some vitamin D however remains in the skin and is activated to
      interact with its vitamin D receptor to control cell proliferation using a
      variety of strategies including interacting with long non-coding RNAs to reduce
      risk of photocarcinogenesis.

PMID- 24665944
TI  - Direct time-resolved spectroscopic observation of arylnitrenium ion reactions
      with guanine-containing DNA oligomers.
AB  - The metabolic activation of a number of aromatic amine compounds to arylnitrenium
      ions that can react with DNA to form covalent adducts has been linked to
      carcinogenesis. Guanine in DNA has been shown to be the main target of N
      containing carcinogens, and many monomeric guanine derivatives have been utilized
      as models for product analysis and spectroscopic investigations to attempt to
      better understand the reaction mechanisms of DNA with arylnitrenium ions.
      However, there are still important unresolved issues regarding how arylnitrenium
      ions attack guanine residues in DNA oligomers. In this article, we employed ns-TA
      and ns-TR(3) spectroscopies to directly observe the reaction of the 2
      fluorenylnitrenium ion with selected DNA oligomers, and we detected an
      intermediate possessing a similar C8 structure as the intermediates produced from
      the reaction of monomeric guanosine derivatives with arylnitrenium ions. Our
      results suggest that the oligomeric structure can lead to a faster reaction rate
      of arylnitrenium ions with guanine residues in DNA oligomers and the reaction of
      arylnitrenium ions take place in a manner similar to reactions with monomeric
      guanosine derivatives.

PMID- 24665945
TI  - Flaws in animal studies exploring statins and impact on meta-analysis.
AB  - BACKGROUND: Animal experiments should be appropriately designed, correctly
      analysed and transparently reported to increase their scientific validity and
      maximise the knowledge gained from each experiment. This systematic review of
      animal experiments investigating statins evaluates their quality of reporting and
      methodological aspects as well as their implications for the conduction of meta
      analyses. METHODS: We searched medline and embase for studies reporting research
      on statins in mice, rats and rabbits. We collected detailed information about the
      characteristics of studies, animals and experimental methods. RESULTS: We
      retrieved 161 studies. A little over half did not report randomisation (55%) and
      most did not describe blinding (88%). All studies reported details on the
      experimental procedure, although many omitted information about animal gender,
      age or weight. Four percent did not report the number of animals used. None
      reported the sample size. Fixed- and random-effects models gave different results
      (ratio of effect size increased by five folds). Heterogeneity was consistently
      substantial within animal models, for which accounting for covariates had minimal
      impact. Publication bias is highly suspected across studies. CONCLUSIONS:
      Although statins showed efficacy in animal models, preclinical studies
      highlighted fundamental problems in the way in which such research is conducted
      and reported. Results were often difficult to interpret and reproduce. Different
      meta-analytic approaches were highly inconsistent: a reliable approach to
      estimate the true parameter was imperceptible. Policies that address these issues
      are required from investigators, editors and institutions that care about the
      quality standards and ethics of animal research.

PMID- 24665946
TI  - Unroofed coronary sinus atrial septal defect: diagnosis by multimodality cardiac
      imaging.

PMID- 24665948
TI  - Actinic damage on the back is significantly determined by MC1R variants and
      previous sun exposure compared with other body sites in a multivariate analysis.
AB  - BACKGROUND: Only recently, site-dependent associations of actinic damage with
      melanoma were identified in our study population. OBJECTIVES: To elucidate the
      diverse aetiologies for actinic damage at different body sites. METHODS: We
      performed multivariate logistic regression analyses to identify independent risk
      factors for actinic damage on the face, hands and the back in 2112 participants
      of central European origin. RESULTS: For actinic damage on the face, age was the
      only risk factor that remained consistently significant in a multivariate
      analysis, whereas actinic damage on the back was predominantly associated with
      number of sunburns, freckles in childhood, holiday weeks and male sex. Moreover,
      we identified a particular significance of MC1R variants and dorsal actinic skin
      damage. CONCLUSIONS: The particular effect of MC1R variants and sun exposure
      during recreational time on dorsal actinic damage indicates that actinic damage
      on the back is more informative regarding susceptibility to sunlight and past sun
      exposure associated with melanoma risk.

PMID- 24665947
TI  - Looking back to the future: predicting in vivo efficacy of small molecules versus
      Mycobacterium tuberculosis.
AB  - Selecting and translating in vitro leads for a disease into molecules with in
      vivo activity in an animal model of the disease is a challenge that takes
      considerable time and money. As an example, recent years have seen whole-cell
      phenotypic screens of millions of compounds yielding over 1500 inhibitors of
      Mycobacterium tuberculosis (Mtb). These must be prioritized for testing in the
      mouse in vivo assay for Mtb infection, a validated model utilized to select
      compounds for further testing. We demonstrate learning from in vivo active and
      inactive compounds using machine learning classification models (Bayesian,
      support vector machines, and recursive partitioning) consisting of 773 compounds.
      The Bayesian model predicted 8 out of 11 additional in vivo actives not included
      in the model as an external test set. Curation of 70 years of Mtb data can
      therefore provide statistically robust computational models to focus resources on
      in vivo active small molecule antituberculars. This highlights a cost-effective
      predictor for in vivo testing elsewhere in other diseases. 

PMID- 24665949
TI  - Evaluating the binding of selected biomolecules to cranberry derived
      proanthocyanidins using the quartz crystal microbalance.
AB  - Despite cranberry being associated with the prevention of bacterial infections
      for over a century, our understanding of the bioavailability and mechanisms by
      which cranberry prevents infection is limited. This study investigates the
      interactions between cranberry proanthocyanidins (CPAC) and human serum proteins
      (albumin, alpha-1-acid glycoprotein, and fibrinogen) that may be encountered
      during CPAC metabolism following ingestion. To better understand how CPAC might
      interfere with bacterial infection, we also examined the interactions between
      CPAC and selected bacterial virulence factors; namely, lipopolysaccharide (LPS)
      and rhamnolipid. The binding of CPAC to the serum proteins, rhamnolipids and LPS
      from Escherichia coli O111:B4 can be described by Langmuir-type isotherms,
      allowing the determination of the apparent adsorption affinity constants, with
      CPAC interacting most strongly with fibrinogen with a binding constant of 2.2 *
      10(8) M(-1). These binding interactions will limit the bioavailability of the
      CPAC at the site of action, an important consideration in designing further
      clinical trials. Furthermore, CPAC interacts with Pseudomonas aeruginosa 10 LPS,
      E. coli O111:B4 LPS, and P. aeruginosa rhamnolipids in fundamentally different
      manners, supporting the theory that cranberry prevents bacterial infections via
      multiple mechanisms. 

PMID- 24665950
TI  - Space use as an indicator of enclosure appropriateness in African wild dogs
      (Lycaon pictus).
AB  - A clear understanding of space use is required to more fully understand
      biological requirements of nonhuman animals in zoos, aid the design of exhibits,
      and maximize the animals' welfare. This study used electivity indexes to assess
      space use of two packs of African wild dogs (Lycaon pictus) and the
      appropriateness of two naturalistic, outdoor enclosures at the San Diego Zoo and
      Bronx Zoo. The results identified enclosure features that were both underutilized
      and overutilized. They suggest that replacing underutilized areas with features
      similar to areas that were overutilized may provide more preferred opportunities
      for the animals. Assessing space use of animals in human care may serve as an
      indicator of enclosure appropriateness and could have welfare implications. By
      looking at the possible reasons for area preferences, animal managers can get an
      idea of where improvements could be made. Designing future exhibits accordingly
      thus can provide possible welfare benefits for the animals concerned. 

PMID- 24665951
TI  - Animal housing and welfare: effects of housing conditions on body weight and
      cortisol in a medium-sized rodent (Cavia aperea).
AB  - Rodents are the most abundant experimental nonhuman animals and are commonly
      studied under standard laboratory housing conditions. As housing conditions
      affect animals' physiology and behavior, this study investigated the effects of
      indoor and outdoor housing conditions on body weight and cortisol level of wild
      cavies, Cavia aperea. The changing housing condition strongly influenced both
      parameters, which are commonly used as indicators for animal welfare. The
      transfer from outdoor to indoor enclosures resulted in a body-weight loss of
      about 8%. In contrast, animals kept indoors showed a substantial weight gain of
      about 12% when they were transferred outdoors. These effects were reversible. To
      substantiate a connection between body-weight changes and the health states of
      the animals, blood basal cortisol concentrations were measured. Animals kept
      outdoors had significantly lower cortisol levels than did animals kept indoors.
      These results imply that indoor conditions have a direct effect on the animals'
      states. The physiological and metabolic consequences as well as potential welfare
      aspects should be taken into account when planning experimental work, especially
      on nondomestic animals. 

PMID- 24665952
TI  - Computer-aided pattern recognition of large reptiles as a noninvasive application
      to identify individuals.
AB  - For large species, the capture and handling of individuals in capture-mark
      recapture studies introduces nonhuman animal welfare issues associated with
      handling, physical marking, and possible wounding due to tag loss. The use of
      photographic identification for these species offers an alternative and less
      invasive marking technique. This study investigated the opportunity offered by
      photo identification to individually mark individuals of a large reptile, the
      perentie (Varanus giganteus), in Australia and therefore avoid the stress of
      physically capturing and handling. Photographs submitted by a remotely located
      community were first validated to confirm whether perenties could be individually
      identified from their spots electronically using a computer program. Computer
      aided selection of unique patterns was found to be appropriate for the
      identification of individuals and confirmed 38 individuals during the sampling
      period. The value of this approach is 2-fold: There is a benefit to animal
      welfare in that handling an animal is not required to capture him or her, thus
      reducing capture-related stress; and confirmation that photo identification of
      distinctive patterns of the perentie is valid and offers a useful option to
      identify individuals of this large species. 

PMID- 24665953
TI  - Investigating some of the factors that influence "consumer" choice when adopting
      a shelter dog in the United kingdom.
AB  - This study examined which characteristics of dogs available at a large rehoming
      organization in the United Kingdom influenced prospective adopters' choices. The
      revealed preference data used to model "consumer" choice were from the Dogs Trust
      rehoming web pages. The analysis of the probability of adoption involved a
      logistic regression model with multiple imputation. The factors that had a
      significant impact on the adopters' choices were age, size, pedigree status, coat
      length, behavior (e.g., fearfulness, adjustment issues), friendliness (toward
      children, dogs, and other pets), and training. This study offers a quantitative
      analysis of adopters' preferences that could prove to be useful for shelter
      personnel and researchers interested in the analysis of companion animal markets.

PMID- 24665954
TI  - Supernumerary teat removal can be avoided in dairy sheep.
AB  - The aim of this work was to determine whether the removal of supernumerary teats
      from dairy sheep when they are born is a useful procedure in the farming routine.
      Ewes were divided into 3 groups according to the number of teats at milking: ewes
      who were born with 2 teats; ewes who were born with 4 teats and had the 2
      supernumerary nipples cut just after birth; and ewes who were born with 4 teats
      and did not have nipple amputation performed. Removal of supernumerary teats at
      lambing produced a significant reduction in milk production during the 2 first
      milking periods (p < .01). There were no differences between ewes with 2 or 4
      teats, which suggests that this procedure is not necessary on dairy sheep farms.
      Because the presence of supernumerary teats is highly heritable, the elimination
      of this trait could be accomplished through selection methods. 

PMID- 24665956
TI  - Potential of long-chain n-3 polyunsaturated fatty acids in melanoma prevention.
AB  - The possible antineoplastic activity of dietary long-chain n-3 polyunsaturated
      fatty acids (LC n-3 PUFAs) has been supported by ample preclinical studies that
      have identified a number of molecular factors and pathways affected by these
      fatty acids and involved in cell growth, apoptosis, invasion, and angiogenesis.
      The aim of this critical review is to assess the current state of knowledge on
      the potential anticancer effects of LC n-3 PUFAs against malignant melanoma, one
      of the most common cancers among Western populations. The results of preclinical
      as well as human observational and interventional studies investigating the
      effects of LC n-3 PUFAs in melanoma were examined. Overall, the analysis of the
      literature reveals that, even though a large body of information is available,
      further effort is needed to identify the main molecular targets of LC n-3 PUFAs
      in melanoma. Moreover, additional well-designed human observational studies are
      essential to shed further light on the issue. The results of these studies could
      provide support and specific information for the development of clinical studies,
      especially those performed in combination with conventional or innovative
      antineoplastic therapies. 

PMID- 24665957
TI  - Update on romosozumab : a humanized monoclonal antibody to sclerostin.
AB  - INTRODUCTION: Disorders with inactivating mutations of the SOST gene result in
      reduced or absent expression of sclerostin and are associated with high bone
      mass. Sclerostin is an important regulator of bone formation due to its
      inhibitory actions in the osteoanabolic Wnt signaling pathway. Advances in
      understanding the mechanisms of action of this signaling molecule have led to the
      development of a pharmacological inhibitor of sclerostin with potential clinical
      applications as an osteoanabolic drug for the treatment of osteoporosis. AREAS
      COVERED: Romosozumab is the first humanized monoclonal sclerostin antibody to be
      tested in clinical trials. Similar to preclinical animal studies with sclerostin
      antibodies, initial clinical studies show that romosozumab increases bone
      formation and bone mineral density. EXPERT OPINION: Blocking sclerostin action
      with romosozumab is a promising new therapeutic approach to osteoanabolic therapy
      of osteoporosis; efficacy and safety data on large controlled studies are
      awaited.

PMID- 24665958
TI  - Neonatal thrombocytopenia: etiology, management and outcome.
AB  - Thrombocytopenia is a very common hematological abnormality found in newborns,
      especially in preterm neonates. Two subgroups can be distinguished: early
      thrombocytopenia, occurring within the first 72 hours of life, and late
      thrombocytopenia, occurring after the first 72 hours of life. Early
      thrombocytopenia is associated with intrauterine growth restriction, whereas late
      thrombocytopenia is caused mainly by sepsis and necrotizing enterocolitis (NEC).
      Platelet transfusions are the hallmark of the treatment of neonatal
      thrombocytopenia. Most of these transfusions are prophylactic, which means they
      are given in the absence of bleeding. However, the efficacy of these transfusions
      in preventing bleeding has never been proven. In addition, risks of platelet
      transfusion seem to be more pronounced in preterm neonates. Because of lack of
      data, platelet transfusion guidelines differ widely between countries. This
      review summarizes the current understanding of etiology and management of
      neonatal thrombocytopenia. 

PMID- 24665959
TI  - Regional and seasonal differences in skin irritation and neurosensitivity in
      Chinese and South Korean women.
AB  - BACKGROUND: China has a great variety of geographical and climatic conditions,
      and several cultural differences exist within the country; thus, understanding
      the regional and seasonal differences that cause skin sensitivities in this
      country is important. OBJECTIVE: The aim of this study was to assess skin
      sensitivity of women from six cities in China and from South Korea during the
      winter and summer seasons to aid the development of suitable and effective
      dermatological products. METHODS: This multicentre study included 754 healthy
      female volunteers, and was conducted in the winter (between January and March)
      and summer (between June and July) of 2011. Patch tests were performed using 0.5%
      sodium lauryl sulphate (SLS) aqueous solution and 0.15% retinol in 1,3-butylene
      glycol on the back of the volunteers. Simultaneously, stinging tests were
      performed on their cheeks by using 5% lactic acid solution and 0.001% capsaicin
      solution, each in a negative control vehicle (distilled water and 10% ethanol
      solution, respectively). RESULTS: The patch test results showed that the subjects
      in Beijing and Shenyang were more sensitive to SLS, retinol and lactic acid in
      the winter than were those in Guangzhou, Shanghai, Wuhan, Chengdu and South
      Korea. The stinging test results revealed that the subjects in Beijing were more
      neurosensitive to lactic acid in the winter; however, during the same season, the
      subjects from Shanghai and Guangzhou were significantly more neurosensitive to
      capsaicin. CONCLUSION: Our observations indicate that skin sensitivity differs
      considerably between women from different parts of China and South Korea. We
      recommend that these differences be considered during the development of cosmetic
      products in these countries.

PMID- 24665960
TI  - Archaeological evidence of validity of fish populations on unexploited reefs as
      proxy targets for modern populations.
AB  - Reef-fish management and conservation is hindered by a lack of information on
      fish populations prior to large-scale contemporary human impacts. As a result,
      relatively pristine sites are often used as conservation baselines for
      populations near sites affected by humans. This space-for-time approach can only
      be validated by sampling assemblages through time. We used archaeological remains
      to evaluate whether the remote, uninhabited Northwestern Hawaiian Islands (NWHI)
      might provide a reasonable proxy for a lightly exploited baseline in the Main
      Hawaiian Islands (MHI). We used molecular and morphological techniques to
      describe the taxonomic and size composition of the scarine parrotfish catches
      present in 2 archaeological assemblages from the MHI, compared metrics of these
      catches with modern estimates of reproductive parameters to evaluate whether
      catches represented by the archaeological material were consistent with
      sustainable fishing, and evaluated overlap between size structures represented by
      the archaeological material and modern survey data from the MHI and the NWHI to
      assess whether a space-for-time substitution is reasonable. The parrotfish
      catches represented by archaeological remains were consistent with sustainable
      fishing because they were dominated by large, mature individuals whose average
      size remained stable from prehistoric (AD approximately 1400-1700) through
      historic (AD 1700-1960) periods. The ancient catches were unlike populations in
      the MHI today. Overlap between the size structure of ancient MHI catches and
      modern survey data from the NWHI or the MHI was an order of magnitude greater for
      the NWHI comparison, a result that supports the validity of using the NWHI
      parrotfish data as a proxy for the MHI before accelerated, heavy human impacts in
      modern times.

PMID- 24665961
TI  - Sleep problems and their relationship to cognitive and behavioral outcomes in
      young children with traumatic brain injury.
AB  - This study examined the effect of traumatic brain injury (TBI) in young children
      on sleep problems and the relationship of sleep problems to neuropsychological
      and psychosocial functioning. Participants were drawn from an ongoing
      longitudinal study of injury in young children recruited from 3 to 6 years of
      age. They constituted three groups: orthopedic injury (OI; n=92), complicated
      mild/moderate TBI (mTBI; n=55); and severe TBI (sTBI; n=20). Caregivers completed
      the Children's Sleep Habits Questionnaire (CSHQ), as well as ratings of
      behavioral adjustment, adaptive functioning, and everyday executive function at
      1, 6, 12, and 18 months postinjury. Retrospective ratings of preinjury sleep and
      psychosocial functioning were obtained at the initial assessment. Children
      completed neuropsychological testing at all occasions. Children with complicated
      mTBI demonstrated more total sleep problems than children with OI at 6 months
      postinjury, but not at 12 or 18 months. Children with sTBI displayed more bedtime
      resistance and shorter sleep duration than those with complicated mTBI or OI at
      several occasions. Across groups, total sleep problems predicted more emotional
      and behavioral problems and worse everyday executive function as rated by parents
      across follow-up occasions. In contrast, sleep problems were generally not
      related to neuropsychological test performance. The results suggest that young
      children with TBI demonstrate more sleep problems than children with injuries not
      involving the head. Sleep problems, in turn, significantly increase the risk of
      poor psychosocial outcomes across time, but are not associated with worse
      neuropsychological test performance.

PMID- 24665962
TI  - Evidence-based guidelines for wise use of electronic games by children.
AB  - Electronic games (e-games) are widely used by children, often for substantial
      durations, yet to date there are no evidence-based guidelines regarding their
      use. The aim of this paper is to present guidelines for the wise use of e-games
      by children based on a narrative review of the research. This paper proposes a
      model of factors that influence child-e-games interaction. It summarises the
      evidence on positive and negative effects of use of e-games on physical activity
      and sedentary behaviour, cardio-metabolic health, musculoskeletal health, motor
      coordination, vision, cognitive development and psychosocial health. Available
      guidelines and the role of guidelines are discussed. Finally, this information is
      compiled into a clear set of evidence-based guidelines, about wise use of e-games
      by children, targeting children, parents, professionals and the e-game industry.
      These guidelines provide an accessible synthesis of available knowledge and
      pragmatic guidelines based on e-game specific evidence and related research. 

PMID- 24665964
TI  - Antimony-doped tin oxide nanorods as a transparent conducting electrode for
      enhancing photoelectrochemical oxidation of water by hematite.
AB  - We report the growth of well-defined antimony-doped tin oxide (ATO) nanorods as a
      conductive scaffold to improve hematite's photoelectrochemical water oxidation
      performance. The hematite grown on ATO exhibits greatly improved performance for
      photoelectrochemical water oxidation compared to hematite grown on flat fluorine
      doped tin oxide (FTO). The optimized photocurrent density of hematite on ATO is
      0.67 mA/cm(2) (0.6 V vs Ag/AgCl), which is much larger than the photocurrent
      density of hematite on flat FTO (0.03 mA/cm(2)). Using H2O2 as a hole scavenger,
      it is shown that the ATO nanorods indeed act as a useful scaffold and enhanced
      the bulk charge separation efficiency of hematite from 2.5% to 18% at 0.4 V vs
      Ag/AgCl. 

PMID- 24665963
TI  - Modeling the fate of Escherichia coli O157:H7 and Salmonella enterica in the
      agricultural environment: current perspective.
AB  - The significance of fresh vegetable consumption on human nutrition and health is
      well recognized. Human infections with Escherichia coli O157:H7 and Salmonella
      enterica linked to fresh vegetable consumption have become a serious public
      health problem inflicting a heavy economic burden. The use of contaminated
      livestock wastes such as manure and manure slurry in crop production is believed
      to be one of the principal routes of fresh vegetable contamination with E. coli
      O157:H7 and S. enterica at preharvest stage because both ruminant and nonruminant
      livestock are known carriers of E. coli O157:H7 and S. enterica in the
      environment. A number of challenge-testing studies have examined the fate of E.
      coli O157:H7 and S. enterica in the agricultural environment with the view of
      designing strategies for controlling vegetable contamination preharvest. In this
      review, we examined the mathematical modeling approaches that have been used to
      study the behavior of E. coli O157:H7 and S. enterica in the manure, manure
      amended soil, and in manure-amended soil-plant ecosystem during cultivation of
      fresh vegetable crops. We focused on how the models have been applied to fit
      survivor curves, predict survival, and assess the risk of vegetable contamination
      preharvest. The inadequacies of the current modeling approaches are discussed and
      suggestions for improvements to enhance the applicability of the models as
      decision tools to control E. coli O157:H7 and S. enterica contamination of fresh
      vegetables during primary production are presented. 

PMID- 24665965
TI  - T-cell co-stimulation through the CD2 and CD28 co-receptors induces distinct
      signalling responses.
AB  - Full T-cell activation critically depends on the engagement of the TCR (T-cell
      receptor) in conjunction with a second signal by co-stimulatory receptors that
      boost the immune response. In the present study we have compared signalling
      patterns induced by the two co-receptors CD2 and CD28 in human peripheral blood T
      cells. These co-receptors were previously suggested to be redundant in function.
      By a combination of multi-parameter phosphoflow cytometry, phosphokinase arrays
      and Western blot analyses, we demonstrate that CD2 co-stimulation induces
      phosphorylation of the TCR-proximal signalling complex, whereas CD28 activates
      distal signalling molecules, including the transcription factors NF-kappaB
      (nuclear factor kappaB), ATF (activating transcription factor)-2, STAT3/5 (signal
      transducer and activator of transcription 3/5), p53 and c-Jun. These signalling
      patterns were conserved in both naive and effector/memory T-cell subsets. We show
      that free intracellular Ca(2+) and signalling through the PI3K (phosphoinositide
      3-kinase)/Akt pathway are required for proper CD28-induced NF-kappaB activation.
      The signalling patterns induced by CD2 and CD28 co-stimulation lead to distinct
      functional immune responses in T-cell proliferation and cytokine production. In
      conclusion, CD2 and CD28 co-stimulation induces distinct signalling responses and
      functional outcomes in T-cells.

PMID- 24665966
TI  - Evaluation of dysprosia aerogels as drug delivery systems: a comparative study
      with random and ordered mesoporous silicas.
AB  - Biocompatible dysprosia aerogels were synthesized from DyCl3.6H2O and were
      reinforced mechanically with a conformal nano-thin-polyurea coating applied over
      their skeletal framework. The random mesoporous space of dysprosia aerogels was
      filled up to about 30% v/v with paracetamol, indomethacin, or insulin, and the
      drug release rate was monitored spectrophotometrically in phosphate buffer (pH =
      7.4) or 0.1 M aqueous HCl. The drug uptake and release study was conducted
      comparatively with polyurea-crosslinked random silica aerogels, as well as with
      as-prepared (native) and polyurea-crosslinked mesoporous silica perforated with
      ordered 7 nm tubes in hexagonal packing. Drug uptake from random nanostructures
      (silica or dysprosia) was higher (30-35% w/w) and the release rate was slower
      (typically >20 h) relative to ordered silica (19-21% w/w, <1.5 h, respectively).
      Drug release data from dysprosia aerogels were fitted with a flux equation
      consisting of three additive terms that correspond to drug stored successively in
      three hierarchical pore sites on the skeletal framework. The high drug uptake and
      slow release from dysprosia aerogels, in combination with their low toxicity,
      strong paramagnetism, and the possibility for neutron activation render those
      materials attractive multifunctional vehicles for site-specific drug delivery. 

PMID- 24665967
TI  - Timing of radiological improvement after steroid therapy in patients with
      autoimmune pancreatitis.
AB  - OBJECTIVE: We retrospectively studied the timing of radiological improvement
      after steroid therapy in patients with autoimmune pancreatitis (AIP). MATERIAL
      AND METHODS: Patients with AIP (n = 31) received steroids followed by diagnostic
      imaging within 1 month. Pancreatic swelling, pancreatic and bile duct features,
      and apparent diffusion coefficient (ADC) were compared before and after
      treatment. The period from treatment initiation to evaluation was divided into
      five phases: early phase (days 3-5), week 1 (days 6 and 7), week 2 (days 8-14),
      week 3 (days 15-21), and week 4 (days 22-28). Five gastroenterologists evaluated
      pancreatic swelling and duct features (good/intermediate/no response), and the
      "good response" rate (response rate) was calculated for each phase. In addition,
      pancreatic volumes were measured with a 3D workstation before and after
      treatment, and the percentage change in volume was calculated. ADC values were
      calculated in 14 patients. RESULTS: The median ratio of pancreatic volume after
      relative to before treatment was 0.89, 0.79, 0.67, 0.59, and 0.47 for early
      phase, week 1, week 2, week 3, and week 4, respectively. The response rate of the
      pancreatic swelling was 37.5%, 57.1%, 83.3%, 100%, and 100%; response rate of the
      pancreatic duct was 0%, 20%, 75%, 75% and 100%; and response rate of the bile
      duct was 0%, 66.7%, 83.3%, 100%, and 80%. The ADC increased after treatment in
      all 14 patients, including the 7 patients evaluated in the early phase.
      CONCLUSIONS: Evaluation of pancreatic swelling and duct features is recommended
      in week 2 and thereafter. The ADC increased soon after treatment initiation,
      suggesting its usefulness for evaluating early treatment responses.

PMID- 24665968
TI  - Mycotic aneurysm and fungal spinal abscess due to tainted steroid injection.

PMID- 24665969
TI  - Remote extradural haematomas following extended transsphenoidal surgery for a
      craniopharyngioma--a case report.
AB  - We present the first recorded case of a remote extradural haematoma following
      extended transsphenoidal surgery (eTSS) for craniopharyngioma. We believe that
      this is a unique complication related to rapid and excessive intracranial
      hypotension caused by acute overdrainage of cerebrospinal fluid (CSF) during the
      eTSS procedure.

PMID- 24665970
TI  - Quantifying activity: a new assay reveals T-cell signalling in tiny skin biopsy
      samples.
AB  - Tissue-invasive T cells are observed in many inflammatory dermatological
      diseases, but in most cases, it is not known how they were attracted, what they
      might recognize, and to which extent they are activated. Answering these
      questions is surely essential for understanding pathogeneses of the diseases. In
      a recent issue of Experimental Dermatology, Smith et al. showed that early
      signalling events in skin-resident T cells may be investigated by multiplex
      immunoprecipitation flow cytometry, even if only few T cells are available from
      skin biopsy samples. This new technology will most likely contribute to
      elucidating the role of skin-invasive T cells and to understanding the pathology
      of dermatological diseases.

PMID- 24665971
TI  - Longitudinal evaluation of fluoride levels in nails of 18-30-month-old children
      that were using toothpastes with 500 and 1100 MUg F/g.
AB  - OBJECTIVES: This study aimed to evaluate the fluoride concentration in the
      fingernails and toenails of children aged 18-30 months during use of fluoride
      containing toothpastes supplemented with calcium glycerophosphate (CaGP) or
      sodium trimetaphosphate (TMP). METHODS: According to the toothpaste used,
      children (n = 56) were randomly assigned into three groups: 500 MUg F/g with 1%
      TMP, 500 MUg F/g with 0.25% CaGP, and 1100 MUg F/g. Fingernails and toenails were
      collected monthly over a period of 330 days, from the beginning of toothpaste
      use. Fluoride concentration in the water consumed by the volunteers and fluoride
      intake from diet and toothpaste were also determined. Fluoride analyses were
      performed with the electrode after hexamethyldisiloxane-facilitated diffusion or
      by the direct method, according to the samples. Data passed normality and
      homoscedasticity tests and were analyzed by 2-way analysis of variance (anova)
      and 1-way anova followed by Student-Newman-Keuls test (P < 0.05). RESULTS:
      Fluoride levels in the fingernails and toenails as well as fluoride intake from
      toothpaste were similar for the groups treated with 500 MUg F/g with 1% TMP and
      500 MUg F/g with 0.25% CaGP toothpastes, but significantly lower than the 1100
      MUg F/g group (P < 0.05). No significant differences were noted among the groups
      regarding fluoride intake from diet and that by water consumed by the volunteers
      (P > 0.05). CONCLUSION: The results of the longitudinal study suggest that the
      level of fluoride present in nails was lower with the use of toothpastes with a
      low fluoride concentration.

PMID- 24665972
TI  - Atrial fibrillation burden estimates derived from intermittent rhythm monitoring
      are unreliable estimates of the true atrial fibrillation burden.
AB  - BACKGROUND: Estimates of atrial fibrillation (AF) burden (AFB) derived from
      intermittent rhythm monitoring (IRM) are increasingly being used as an outcome
      measure after therapeutic interventions; however, their accuracy has never been
      validated. The aim of this study was to compare IRM-derived AFB estimates to the
      true AFB as measured by implantable continuous monitoring (CM) devices. METHODS:
      Rhythm histories from 647 patients (mean AFB: 12 +/- 22%; 687 patient.years) with
      CM devices were analyzed. IRM of various frequencies and durations were simulated
      and the obtained IRM-derived AF burdens were compared to the true AFB measured by
      CM. RESULTS: The relative error of the IRM burden estimates was dependent on the
      IRM length (P < 0.001), frequency of IRM (P < 0.001), the true AFB (P < 0.001),
      and its temporal aggregation (AF density, P < 0.001). In paroxysmal AF patients,
      the relative error even with aggressive IRM strategies was >80% of the true AFB.
      The relative error decreased with higher true AF burdens, lower AF densities, and
      higher IRM frequency or duration (P < 0.001). However, even in patients with high
      AF burdens and/or low AF densities, IRM estimates of AFB significantly deviated
      from the true AFB (relative error >20%, P < 0.001) and resulted in a substantial
      measurement error. CONCLUSION: IRM-derived AFB estimates are unreliable
      estimators of the true AFB. Particularly for paroxysmal AF patients, IRM-derived
      AFB estimates should not be used to evaluate outcomes after AF interventions.

PMID- 24665974
TI  - On the effectiveness of remediating groundwater contamination: waiting for the
      black swan.

PMID- 24665973
TI  - The word-length effect in reading: a review.
AB  - The finding that visual processing of a word correlates with the number of its
      letters has an extensive history. In healthy subjects, a variety of methods,
      including perceptual thresholds, naming and lexical decision times, and ocular
      motor parameters, show modest effects that interact with high-order effects like
      frequency. Whether this indicates serial processing of letters under some
      conditions or indexes low-level visual factors related to word length is unclear.
      Word-length effects are larger in pure alexia, where they probably reflect a
      serial letter-by-letter strategy, due to failure of lexical whole-word processing
      and variable dysfunction in letter encoding. In pure alexia, the word-length
      effect is systematically related to mean naming latency, with the word-length
      effect becoming proportionally greater as naming latency becomes more delayed in
      severe cases. Other conditions may also generate enhanced word-length effects.
      This occurs in right hemianopia: Computer simulations suggest a criterion of 160
      ms/letter to distinguish hemianopic dyslexia from pure alexia. Normal reading
      development is accompanied by a decrease in word-length effects, whereas
      persistently elevated word-length effects are characteristic of developmental
      dyslexia. Little is known about word-length effects in other reading disorders.
      We conclude that the word-length effect captures the efficiency of the perceptual
      reading process in development, normal reading, and a number of reading
      disorders, even if its mechanistic implications are not always clear.

PMID- 24665975
TI  - Facts, presumptions, and myths on the solvent-free and catalyst-free Biginelli
      reaction. What is catalysis for?
AB  - The current manuscript describes the role and importance of catalysis and solvent
      effects for the Biginelli multicomponent reaction. The overwhelming number of new
      catalysts and conditions recently published for the Biginelli synthesis,
      including in some manuscripts entitled "catalyst-free" and/or "solvent-free" have
      incentivized controversies and hot debates regarding the importance of developing
      new catalysts and reaction conditions to perform this very important
      multicomponent reaction. These so-called "catalyst-free" reports have generated
      much confusion in the field, requiring urgent elucidations. In this manuscript,
      we exemplify, demystify, and discuss the crucial role of catalysis, solvent
      effects, mechanisms, kinetics, facts, presumptions, and myths associated with the
      Biginelli reaction aiming to avoid current and future confusion and to stimulate
      new approaches.

PMID- 24665976
TI  - Sun protective behaviour of vacationers spending holidays in the tropics and
      subtropics.
AB  - BACKGROUND: The development of malignant melanoma has been associated with
      intense episodic sun exposure, as it typically occurs during holidays in high
      ultraviolet (UV)-index countries. OBJECTIVES: To investigate sun protective
      behaviour and sunburn experience of vacationers spending holidays in the tropics
      or subtropics. METHODS: Using standardized face-to-face interviews, we conducted
      cross-sectional surveys among air passengers waiting in the departure or the
      baggage claim area at the Airport Basel-Mulhouse (Switzerland/France), and among
      vacationers waiting for pretravel health advice at a travel clinic in Basel
      (Switzerland). RESULTS: We completed 533, 324 and 308 interviews with departing
      air passengers, returning air passengers and vacationers at the travel clinic,
      respectively. The interviews revealed widespread misconceptions about how to
      prepare the skin for the sun before holidays (e.g. pretanning in the solarium).
      At the holiday destination, almost all respondents used sunscreen, whereas
      wearing protective clothing and seeking shade were less practised. Among the
      returning air passengers, 44% had got sunburnt during their holiday stay.
      CONCLUSIONS: The sunburn rate among returning vacationers was alarmingly high.
      Skin cancer prevention campaigns and pretravel health advice should tackle
      misconceptions regarding the preparation of the skin for the sun, and emphasize
      the significance of covering up and seeking shade.

PMID- 24665977
TI  - The influence of the region of interest width on two-dimensional speckle tracking
      based measurements of strain and strain rate.
AB  - AIMS: There are significant variations in the published normal values of two
      dimensional speckle tracking-derived strain and strain rate. These occur even
      when authors use the same software. To measure strain, the operator creates a
      region of interest (ROI) to define the myocardium to be analyzed. The purpose of
      this study was to test the hypothesis that measurements vary significantly with
      the chosen ROI width. METHODS AND RESULTS: In 20 healthy subjects (11 males, mean
      age 17.6 +/- 6.18 years) an apical four-chamber view (4CH) and parasternal short
      axis view (SAX) were analyzed. Initially ROI width was set automatically by the
      software. Two subsequent measurements were obtained from each cine loop by
      choosing the ROI width one step narrower and one step wider than the automatic
      ROI width. The mean differences between the measurements of narrower and
      automatic ROI and between automatic and wider ROI were -1.8 +/- 0.7% and -0.9 +/-
      0.5% for global longitudinal strain (SL), -2.2 +/- 0.6% and -1.7 +/- 0.7% for
      global circumferential strain (SC), -0.10 +/- 0.06/sec and -0.07 +/- 0.06/sec for
      global longitudinal strain rate (SrL), and -0.15 +/- 0.09/sec and -0.12 +/-
      0.07/sec for global circumferential strain rate (SrC) (all P < 0.000). This
      corresponds to a relative difference to the mean of both measurements of -4.4 to 
      11.0%. CONCLUSION: Layer-specific myocardial deformation and curvature dependency
      lead to an inverse correlation between the chosen ROI width and strain and strain
      rate measurements. Just one step of ROI-width change leads to a significant bias.
      Precise ROI-width definition is essential but technical factors limit its
      feasibility.

PMID- 24665978
TI  - pH-sensitive fluorescent hepatocyte-targeting multilayer polyelectrolyte hollow
      microspheres as a smart drug delivery system.
AB  - Novel multilayer polyelectrolyte hollow microspheres with pH-sensitive
      fluorescence and hepatocyte-targeting functions were successfully fabricated via
      a layer-by-layer (LbL) assembly of fluorescein isothiocyanate (FITC)-modified
      chitosan (CSFITC) and sodium hyaluronate (HA) (as the polycation and polyanion,
      respectively) on polystyrene sulfonate (PSS) templates with galactosylated
      chitosan (GC) as the outermost layer; after etching the templates by dialysis,
      the aim was to use the microspheres to target hepatocytes specifically. TEM
      analysis revealed that they have a hollow structure with a particle size of about
      260 nm, and DLS analysis demonstrated that they have pH and ionic strength dual
      responsive characteristics. The hollow microspheres showed pH-sensitive
      fluorescence at a very low concentration by fluorescent emission spectra. MTT
      assays revealed that doxorubicin (a water-insoluble anticancer drug)-loaded
      (CSFITC/HA)4/GC hollow microspheres can specifically target hepatocytes and
      exhibit favorable cytocompatibility. Three typical model drugs were loaded into
      the (CSFITC/HA)4/GC hollow microspheres, and their drug-release kinetics in
      simulated body fluid (SBF) were estimated with different mathematical models. The
      results demonstrated that the drug-loading mechanism is chemosorption and the
      primary governing force for drug release is diffusion. Thus, the designed hollow
      microspheres are expected to be used for the diagnosis and therapy of hepatic
      cancer. 

PMID- 24665979
TI  - Anthropometric and body composition changes during expeditions at high altitude.
AB  - The purpose of this study is to investigate separately in the two sexes the
      physical adaptations associated to exposure to high altitude in a sample of 18
      nonacclimatized Caucasian subjects (10 males and 8 females, 22-59 years) who
      participated to scientific expeditions to Himalaya up to the Pyramid Laboratory
      (5050 m, Nepal) or Everest North Base Camp (5300 m, Tibet). Anthropometric traits
      (body height and weight, eight girths and six skinfolds) were collected according
      to standard procedures, before departure at sea level, during ascent (at altitude
      > 4000 m above sea level), and after return to low altitude. Body composition was
      assessed by means of the skinfold method. Both sexes lost on average 4.0% of
      initial body mass, corresponding to 7.6% of fat mass and 3.5% of fat free mass in
      males, and to 5.0% of fat mass and 3.6% of fat free mass in females. Average fat
      mass loss was greater in males than in females. Initial fat mass percentage was
      positively correlated to fat mass loss and negatively to FFM loss in males only,
      thus at HA leanest subjects lost more FFM and less FM than the fattest ones.
      Adaptations were faster in males than in females. In conclusion, the present
      research describes significant adaptations to high altitude, in terms of body
      weight reduction, regardless of the amount of performed physical activity.

PMID- 24665980
TI  - Corticotropin-releasing hormone expression in patients with intrahepatic
      cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial
      experience.
AB  - OBJECTIVE: Corticotropin-releasing hormone (CRH) is one of the most potent
      vasodilatory factors in the human feto-placental circulation. The expression of
      CRH was significantly down-regulated in patients with intrahepatic cholestasis of
      pregnancy (ICP). METHODS: One hundred pregnant women diagnosed with ICP at 34
      34(+6) weeks of gestation agreed to participate in this prospective nested case
      control study. Thirty ICP patients were finally recruited in this study, with 16
      cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in
      the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum
      samples were obtained in diagnosis and at 37-37(+6) weeks of gestation. Placental
      tissues were obtained from participants after delivery. ELISA, enzymatic
      colorimetric and Western blotting were used to evaluate the concentrations of
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid
      (TBA) and CRH in maternal serum and expression of CRH in placenta tissues.
      RESULTS: The UDCA group had greater reduction in maternal serum ALT, AST and TBA
      levels in ICP patients (all p < 0.01). Maternal serum CRH concentrations in the
      UDCA group after treatment (122.10 +/- 44.20) pg/ml was significantly higher than
      pretreatment (95.45 +/- 26.47) pg/ml (p < 0.01). After treatment, maternal serum
      CRH concentrations of the UDCA group (122.10 +/- 44.20) pg/ml was significantly
      higher than in the control group (80.71 +/- 41.10) pg/ml (p < 0.01). Placental
      CRH expression in the UDCA group (2.79 +/- 1.72) was significantly higher than in
      the control group (0.69 +/- 0.36) (p < 0.01). CONCLUSIONS: Maternal serum and
      placental CRH expression in ICP patients were up-regulated after treatment of
      UDCA. The up-regulation of CRH expression after UDCA treatment may play an
      important role in the therapeutic mechanism of ICP. All patients recruited in
      this study had severe cholestasis (TBA >= 40 umol/L). Further studies are
      warranted in different gestational weeks and TBA levels to provide more evidence
      for the correlation between UDCA treatment and CRH expression in ICP patients.

PMID- 24665981
TI  - Diamond Blackfan anemia: a model for the translational approach to understanding
      human disease.
AB  - Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome. As
      with the other rare inherited bone marrow failure syndromes, the study of these
      disorders provides important insights into basic biology and, in the case of DBA,
      ribosome biology; the disruption of which characterizes the disorder. Thus DBA
      serves as a paradigm for translational medicine in which the efforts of
      clinicians to manage DBA have informed laboratory scientists who, in turn, have
      stimulated clinical researchers to utilize scientific discovery to provide
      improved care. In this review we describe the clinical syndrome Diamond Blackfan
      anemia and, in particular, we demonstrate how the study of DBA has allowed
      scientific inquiry to create opportunities for progress in its understanding and
      treatment. 

PMID- 24665982
TI  - Nucleic acid vaccines: prospects for non-viral delivery of mRNA vaccines.
AB  - INTRODUCTION: Nucleic acid-based vaccines are being developed as a means to
      combine the positive attributes of both live-attenuated and subunit vaccines.
      Viral vectors and plasmid DNA vaccines have been extensively evaluated in human
      clinical trials and have been shown to be safe and immunogenic, although none
      have been licensed for human use. More recently, mRNA-based vaccine alternatives
      have emerged and might offer certain advantages over their DNA-based
      counterparts. AREAS COVERED: This review describes the two main categories of
      mRNA vaccines: conventional non-amplifying and self-amplifying mRNA. It
      summarizes the initial clinical proof-of-concept studies and outlines the
      preclinical testing of the next wave of innovations for the technology. Finally,
      this review highlights the versatile functionality of the mRNA molecule and
      introduces opportunities for future improvements in vaccine design. EXPERT
      OPINION: The prospects for mRNA vaccines are very promising. Like other types of
      nucleic acid vaccines, mRNA vaccines have the potential to combine the positive
      attributes of live attenuated vaccines while obviating many potential safety
      limitations. Although data from initial clinical trials appear encouraging, mRNA
      vaccines are far from a commercial product. These initial approaches have spurred
      innovations in vector design, non-viral delivery, large-scale production and
      purification of mRNA to quickly move the technology forward. Some improvements
      have already been tested in preclinical models for both prophylactic and
      therapeutic vaccine targets and have demonstrated their ability to elicit potent
      and broad immune responses, including functional antibodies, type 1 T helper
      cells-type T cell responses and cytotoxic T cells. Though the initial barriers
      for this nucleic acid vaccine approach seem to be overcome, in our opinion, the
      future and continued success of this approach lies in a more extensive evaluation
      of the many non-viral delivery systems described in the literature and gaining a
      better understanding of the mechanism of action to allow rational design of next
      generation technologies.

PMID- 24665984
TI  - The role of civil society in recalibrating conservation science incentives.

PMID- 24665985
TI  - Close to me: the effect of asymmetrical environments on spatial attention.
AB  - Attention can be captured by distractors and can affect performance. To examine
      whether asymmetrical distractors, such as a wall, affect spatial attention,
      Experiment 1 required participants (n = 20) to determine the relative length of
      pre-bisected lines when a temporary barrier was placed close to the left or right
      sides of the display. Post-hoc tests showed that attention was drawn towards
      left, but not right, walls. Experiment 2 (n = 18) sought to increase this effect
      using a solid brick wall rather than a temporary barrier. Instead of
      strengthening the result, no effect of barrier was observed. A non-effect was
      also observed in Experiment 3 (n = 18) when participants moved a cursor to the
      line's middle. Finally, Experiment 4 (n = 26) showed that asymmetrical barriers
      had no effect on visual search. While the data showed some evidence that
      attention is distracted by walls placed to the left, this effect is weak and task
      specific. PRACTITIONER SUMMARY: The ability to monitor critical information on
      displays can be affected by asymmetrical distractors. In many workplaces, a
      display may be placed alongside a wall. This study explored whether a wall placed
      to the left/right affects spatial attention. A weak, task-specific, attraction
      effect was observed for walls on the left.

PMID- 24665986
TI  - Core-shell heterojunction of silicon nanowire arrays and carbon quantum dots for
      photovoltaic devices and self-driven photodetectors.
AB  - Silicon nanostructure-based solar cells have lately intrigued intensive interest
      because of their promising potential in next-generation solar energy conversion
      devices. Herein, we report a silicon nanowire (SiNW) array/carbon quantum dot
      (CQD) core-shell heterojunction photovoltaic device by directly coating Ag
      assisted chemical-etched SiNW arrays with CQDs. The heterojunction with a barrier
      height of 0.75 eV exhibited excellent rectifying behavior with a rectification
      ratio of 10(3) at +/-0.8 V in the dark and power conversion efficiency (PCE) as
      high as 9.10% under AM 1.5G irradiation. It is believed that such a high PCE
      comes from the improved optical absorption as well as the optimized carrier
      transfer and collection capability. Furthermore, the heterojunction could
      function as a high-performance self-driven visible light photodetector operating
      in a wide switching wavelength with good stability, high sensitivity, and fast
      response speed. It is expected that the present SiNW array/CQD core-shell
      heterojunction device could find potential applications in future high
      performance optoelectronic devices. 

PMID- 24665987
TI  - Graphene size control via a mechanochemical method and electroresponsive
      properties.
AB  - Highly dispersible graphene oxide (GO) sheets of uniform submicrometer size were
      successfully fabricated from pristine graphite using a simple mechanochemical
      process. The GO flake morphology was transformed into a spherical form, and the
      density was decreased slightly via the ball-milling process. Ball-milled GO can
      be used as an electrorheological (ER) material because of its small particle
      size, low conductivity, and outstanding dispersibility in silicone oil. We found
      that the 2-h ball-milled GO-based ER fluid had the best ER performance (shear
      stress of 78.5 Pa and 630% ER efficiency), which was double that of the nonmilled
      GO-based ER fluid. The response time to form a fibrillar structure along the
      applied electric field direction and the recovery time to the starting level
      decreased with increasing ball-milling time. Additionally, the retarded settling
      velocity of isolated GO sheets and the electrostatic repulsion between oxygen
      functional groups on the GO sheets combined to improve the antisedimentation
      property. The ability to control the size of graphene sheets is a great
      opportunity to advance graphene commercialization in a high-quality, scalable
      production setting. 

PMID- 24665988
TI  - Analysis of selected volatile organic compounds in split and nonsplit swiss
      cheese samples using selected-ion flow tube mass spectrometry (SIFT-MS).
AB  - Splits/cracks are recurring product defects that negatively affect the Swiss
      cheese industry. Investigations to understand the biophysicochemical aspects of
      these defects, and thus determine preventive measures against their occurrence,
      are underway. In this study, selected-ion, flow tube mass spectrometry was
      employed to determine the volatile organic compound (VOC) profiles present in the
      headspace of split compared with nonsplit cheeses. Two sampling methodologies
      were employed: split compared with nonsplit cheese vat pair blocks; and
      comparison of blind, eye, and split segments within cheese blocks. The
      variability in VOC profiles was examined to evaluate the potential biochemical
      pathway chemistry differences within and between cheese samples. VOC profile
      inhomogeneity was most evident in cheeses between factories. Evaluation of
      biochemical pathways leading to the formation of key VOCs differentiating the
      split from the blind and eye segments within factories indicated release of
      additional carbon dioxide by-product. These results suggest a factory-dependent
      cause of split formation that could develop from varied fermentation pathways in
      the blind, eye, and split areas within a cheese block. The variability of VOC
      profiles within and between factories exhibit varied biochemical fermentation
      pathways that could conceivably be traced back in the making process to identify
      parameters responsible for split defect. 

PMID- 24665989
TI  - Genomic full-length sequence of two novel HLA-DRB1 alleles, DRB1*15:01:01:03 and
      DRB1*15:01:01:04, identified by cloning and sequencing.

PMID- 24665990
TI  - Acute pancreatitis in children: a tertiary hospital report.
AB  - INTRODUCTION: The incidence of acute pancreatitis (AP) in children has increased
      significantly in the past two decades. OBJECTIVE: All cases of AP, acute
      recurrent pancreatitis (ARP), and chronic pancreatitis examined between May 2002
      and May 2012 at Hospital de Braga, Portugal, were reviewed. MATERIAL AND METHODS:
      Patients were identified by searching the hospital's electronic discharge records
      for the International Classification of Disease, Ninth Revision (ICD-9) code
      577.0 (acute pancreatitis). ARP was considered as two or more episodes of AP per
      year or more than three episodes over a lifetime with intervening return to
      baseline. The following data were analyzed: demographic information, clinical,
      laboratory and imaging test results, etiology of pancreatitis, medical and
      surgical management, length of hospitalization, and outcome. The clinical and
      laboratory factors used in the pediatric acute pancreatitis severity score system
      and computed tomography severity index (CTSI) score were compared between
      patients with mild and severe disease. RESULTS: A total of 37 patients, 31
      episodes of AP and 6 patients with ARP, were documented. The most prevalent
      etiologies were biliary stones/sludge (24.3%) and trauma (16.2%). Admission
      elevated white blood cell count (p=0.011), 48-h trough calcium (p=0.007), and 48
      h rise in blood urea nitrogen (p=0.025) correlated significantly with disease
      severity. CTSI on admission had a score below 4 in three patients with severe
      disease. CONCLUSION: This Portuguese pediatric pancreatitis report highlights the
      multiple and complex etiology of this disease. Better pediatric scoring systems
      and management algorithms are needed.

PMID- 24665991
TI  - The nerve of McKenzie: anatomic study with application to intradural rhizotomy
      for spasmodic torticollis.
AB  - INTRODUCTION: Medically recalcitrant spasmodic torticollis may necessitate
      surgical intervention. One procedure used for this pathologic entity is
      intradural rhizotomy. However, some patients are symptomatic, perhaps due to an
      overlooked or underappreciated nerve of McKenzie. The authors' goal was to
      further elucidate the anatomy of this nerve of the craniocervical junction.
      MATERIALS AND METHODS: Fifteen adult cadavers (30 sides) underwent microsurgical
      dissection and observations of the nerve of McKenzie. Morphometrics were
      performed and anatomic relationships were documented under surgical
      magnification. RESULTS: The nerve of McKenzie was found on 70% of sides and was
      always a single branch. Average length was 5.2 mm for left sides and 6 mm for
      right sides. Average diameter was 0.9 mm (0.5-1.2 mm). In two specimens, the
      nerve was found bilaterally. It pierced the first denticulate ligament on 11
      sides (52.4%) and travelled through its two prongs on three sides (14.3%) to
      connect to the anteriorly placed C1 ventral root. On five sides, it was in
      intimate contact with the adventitia of the vertebral artery. It was more common
      on right sides and in males, and this was statistically significant. CONCLUSIONS:
      The authors identified the nerve of McKenzie in most specimens. This nerve, if
      overlooked during surgical treatment of spasmodic torticollis, may result in
      continued symptoms. The nerve of McKenzie was often concealed within the
      denticulate ligament or adventitia of the vertebral artery. The authors hope the
      data presented here will aid neurosurgeons and decrease complications in patients
      who undergo neurotomy for spasmodic torticollis.

PMID- 24665992
TI  - Implantable defibrillators with enhanced detection algorithms: detection
      performance and safety results from the PainFree SST study.
AB  - BACKGROUND: Implantable defibrillators (ICD) are highly effective in reducing
      arrhythmia-related mortality. ICD shock therapy has been shown to increase
      psychological distress, health care utilization, and is associated with increased
      mortality. The Protecta ICDs (Medtronic Inc., Minneapolis, MN, USA) have
      algorithms designed to reduce unnecessary and inappropriate shock therapy.
      METHODS AND RESULTS: The PainFree SmartShockTM Technology (PainFree SST) study is
      a prospective, multicenter, clinical trial with two consecutive phases, a
      premarket phase safety study and a postmarket phase effectiveness study. We
      report the results of the PainFree SST safety study. The premarket phase aimed to
      investigate safety in the first year postimplant, and to determine if the novel
      algorithms (T-wave discrimination, right ventricular lead noise discrimination
      and confirmation+) affect appropriate ventricular fibrillation (VF) detection.
      Patients (total: n = 246 [male 78%, mean age 63 year, primary prevention
      indication in 76%]) were implanted either with a Protecta XT dual-chamber ICD (n
      = 114 [46%]) or a defibrillator with cardiac resynchronization therapy (n = 132
      [54%]). Appropriate VF detection was measured during VF induction at implantation
      when the novel algorithms were programmed ON. A two-second delay in VF detection
      was classified as clinically significant. No delay in VF detection was observed
      with all algorithms programmed ON. No unanticipated serious adverse device
      effects occurred during first year postimplant. CONCLUSION: The results of the
      premarket phase of the PainFree SST trial demonstrate the safety of the Protecta
      XT defibrillators. Detection of induced VF was not delayed with SmartShockTM
      algorithms ON.

PMID- 24665994
TI  - Effect of the regional environment on the skin properties and the early wrinkles
      in young Chinese women.
AB  - BACKGROUND: There are ethnic differences in the skin characteristics, also the
      skin is susceptible to be influenced by the external environment such as UV
      radiation and the climates. It can be shown that the skin in same race or twins
      varies by the environment. OBJECTIVES: This study was designed to investigate the
      skin characteristics and the early wrinkles of young Chinese women from four
      different regions, and to identify the correlation among the wrinkles, the other
      skin characteristics, and environmental conditions. METHODS: A total of 441
      healthy Chinese women aged between 20 and 35 years participated in the study: 110
      from Beijing, 110 from Shanghai, 111 from Wuhan, and 110 from Guangzhou. The skin
      hydration, sebum contents, TEWL, pH, elasticity, and wrinkles were measured on
      the crow's feet area. RESULTS: There were regional differences in the skin
      characteristics and the wrinkles. Beijing women had dry skin and more wrinkles,
      but Guangzhou women had high sebum contents, low pH, and less wrinkles (P <
      0.01). Shanghai women's TEWL and Wuhan's women's skin elasticity were higher
      compared with that of women from other regions. The wrinkles' form (area, depth,
      and length) was different from region to region. Beijing women's wrinkles were
      deep and large, but Guangzhou women's wrinkles were shallow and small. The skin
      physical parameters that influenced the wrinkles were low sebum content and
      hydration, high TEWL, and pH (P < 0.05). CONCLUSION: In the Chinese women aged 20
      35 years, the skin was influenced by the climates, so they had regionally a
      different skin. The skin hydration, sebum contents, TEWL, and pH can affect the
      early wrinkle formation than skin elasticity.

PMID- 24665996
TI  - Modified nonsink equation for permeability estimation in cell monolayers:
      comparison with standard methods.
AB  - Cell culture permeability experiments are valuable tools in drug development and
      candidate selection, but the monolayer preparation protocols and the calculations
      procedures can affect the permeability estimation. Hence, standardization and
      method suitability demonstration are necessary steps for using permeability data
      for regulatory and in vivo prediction purposes. Much attention is usually paid to
      experimental procedure validation and less to the mathematical analysis of the
      results although the standard equations used imply several assumptions that many
      times do not hold. The aim of this study was to use a simulation strategy to
      explore the performance of a new proposed modified nonsink equation (MNS) for
      unidirectional apparent permeability estimation in different types of profiles
      (of cumulative drug amounts versus time) including those in which the initial
      permeation rate is altered, considering several levels of experimental
      variability. The second objective was to compare the MNS method with the
      classical sink and nonsink approaches and finally to explore its usefulness for
      BCS classification. Real data from permeability experiments representing atypical
      profiles have been used for fitting with the three approaches, MNS, sink, and
      nonsink equations, in order to validate the performance of the new proposed
      model. The results demonstrated that the MNS method is a precise and accurate
      equation for calculating the apparent unidirectional permeability in any type of
      profile and different scenarios of variability, in any sink and nonsink
      conditions, while the standard nonsink equation fails in obtaining good
      permeability estimations in those situations in which the initial permeation rate
      is altered. Linear regression models (S and SC) are not valid under nonsink
      conditions, as expected, as the underlying assumptions (sink conditions) do not
      hold, but also in situations in which sink conditions are fulfilled but the
      system variability is high. 

PMID- 24665995
TI  - Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and
      interleukin-6 during treatment for rheumatoid arthritis.
AB  - The Janus kinase inhibitor tofacitinib is currently being investigated as a
      disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo
      effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase
      serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from
      110.5 +/- 118.5 MUg/ml (mean +/- standard deviation) at treatment initiation to
      15.3 +/- 13.3 MUg/ml after 4 weeks treatment with tofacitinib. The reduction in
      SAA levels was greater in patients receiving tofacitinib plus methotrexate
      compared with those receiving tofacitinib monotherapy. Tofacitinib was also
      associated with reduced serum interleukin (IL)-6, but had no effect on serum
      levels of soluble IL-6 receptor. Patients were divided into groups with adequate
      (normalization) and inadequate SAA responses (without normalization). Serum IL-6
      levels were reduced more in the group with adequate SAA response compared with
      those with inadequate SAA response. These results suggest that tofacitinib down
      regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA
      levels in patients with active RA. The ability to regulate elevated serum IL-6
      and SAA levels may explain the anti-inflammatory activity of tofacitinib. 

PMID- 24665997
TI  - Three in the spotlight: Photoinduced stereoselective synthesis of (Z)
      acyloxyacrylamides through a multicomponent approach.
AB  - We report a straightforward approach to synthesize 2-acyloxyacrylamides, which
      are useful synthons in organic synthesis. This involves a photoactivated
      multicomponent reaction, performed both in batch and under continuous flow
      conditions. This process affords the desired compounds in a stereoselective
      fashion from readily available starting materials in one step, without the aid of
      metal catalysis. This paper illustrates the preliminary work, the extensive
      experiments carried out to understand the limitations of the approach, and the
      optimization of the conditions for the synthesis of these particular captodative
      olefins.

PMID- 24665998
TI  - Semi-arid aquifer responses to forest restoration treatments and climate change.
AB  - The purpose of this study was to develop an interpretive groundwater-flow model
      to assess the impacts that planned forest restoration treatments and anticipated
      climate change will have on large regional, deep (>400 m), semi-arid aquifers.
      Simulations were conducted to examine how tree basal area reductions impact
      groundwater recharge from historic conditions to 2099. Novel spatial analyses
      were conducted to determine areas and rates of potential increases in groundwater
      recharge. Changes in recharge were applied to the model by identifying zones of
      basal area reduction from planned forest restoration treatments and applying
      recharge-change factors to these zones. Over a 10-year period of forest
      restoration treatment, a 2.8% increase in recharge to one adjacent groundwater
      basin (the Verde Valley sub-basin) was estimated, compared to conditions that
      existed from 2000 to 2005. However, this increase in recharge was assumed to
      quickly decline after treatment due to regrowth of vegetation and forest
      underbrush and their associated increased evapotranspiration. Furthermore,
      simulated increases in groundwater recharge were masked by decreases in water
      levels, stream baseflow, and groundwater storage resulting from surface water
      diversions and groundwater pumping. These results indicate that there is an
      imbalance between water supply and demand in this regional, semi-arid aquifer.
      Current water management practices may not be sustainable into the far future and
      comprehensive action should be taken to minimize this water budget imbalance. 

PMID- 24665999
TI  - Cardiac function and its evolution with pulmonary vasodilator therapy: a
      myocardial deformation study.
AB  - Speckle tracking echocardiography-derived myocardial strain has useful clinical
      applications in adults with pulmonary hypertension (PH) as well as preterm
      infants with chronic lung disease. It is considered more sensitive compared to
      conventional indices. This report presents a 3-month-old infant with PH and poor
      right ventricular function who was treated with inhaled nitric oxide. Myocardial
      strain was noted to be impaired with paradoxical segmental strain. Impairment in
      strain improved after inhaled nitric therapy. Strain analysis can help improve
      understanding of cardiac adaptation in critical clinical situations. 

PMID- 24666000
TI  - Therapeutic potential of carbohydrate-based polymeric and nanoparticle systems.
AB  - INTRODUCTION: Carbohydrates are key participants in many biological processes
      including reproduction, inflammation, signal transmission and infection. Their
      biocompatibility and ability to be recognized by cell-surface receptors
      illustrate their potential therapeutic applications. alphaYet, they are not ideal
      candidates because they are complex and tedious to synthesize. However, recent
      advances in the field of polymer science and nanotechnology have led to the
      design of biologically relevant carbohydrate mimics for therapeutic uses. This
      review focuses mainly on the therapeutic potential of glycopolymers and
      glyconanoparticles (GNPs). AREAS COVERED: The significance of engineered
      glycopolymers and GNPs as nanomedicine is highlighted in areas such as targeted
      drug delivery, gene therapy, signal transduction, vaccine development, protein
      stabilization and anti-adhesion therapy. EXPERT OPINION: Major effort should be
      focused towards the design and synthesis of more complex and biologically
      relevant carbohydrate mimics in order to have a better understanding of the
      carbohydrate-carbohydrate and carbohydrate-protein interactions. The full
      therapeutic potential of these carbohydrate-based polymeric and nanoparticles
      systems can be achieved once the pivotal participation of the carbohydrates in
      biological systems is clarified.

PMID- 24666001
TI  - Predicting the need for muscle flap salvage after open groin vascular procedures:
      a clinical assessment tool.
AB  - Groin wound complications after open vascular surgery procedures are common,
      morbid, and costly. The purpose of this study was to generate a simple,
      validated, clinically usable risk assessment tool for predicting groin wound
      morbidity after infra-inguinal vascular surgery. A retrospective review of
      consecutive patients undergoing groin cutdowns for femoral access between 2005
      2011 was performed. Patients necessitating salvage flaps were compared to those
      who did not, and a stepwise logistic regression was performed and validated using
      a bootstrap technique. Utilising this analysis, a simplified risk score was
      developed to predict the risk of developing a wound which would necessitate
      salvage. A total of 925 patients were included in the study. The salvage flap
      rate was 11.2% (n = 104). Predictors determined by logistic regression included
      prior groin surgery (OR = 4.0, p < 0.001), prosthetic graft (OR = 2.7, p <
      0.001), coronary artery disease (OR = 1.8, p = 0.019), peripheral arterial
      disease (OR = 5.0, p < 0.001), and obesity (OR = 1.7, p = 0.039). Based upon the
      respective logistic coefficients, a simplified scoring system was developed to
      enable the preoperative risk stratification regarding the likelihood of a
      significant complication which would require a salvage muscle flap. The c
      statistic for the regression demonstrated excellent discrimination at 0.89. This
      study presents a simple, internally validated risk assessment tool that
      accurately predicts wound morbidity requiring flap salvage in open groin vascular
      surgery patients. The preoperatively high-risk patient can be identified and
      selectively targeted as a candidate for a prophylactic muscle flap.

PMID- 24666002
TI  - Alterations in different indices of skeletal health after prolonged residency at
      high altitude.
AB  - AIMS: The aim of this study was to evaluate the effect of prolonged residency at
      high altitude (HA) on different indices of bone health in sea level (SL)
      residents staying at an altitude of 3450 m for 4 months to 1 year. The assessment
      of bone health parameters included multisite quantitative bone speed of sound
      (SOS), and markers of bone metabolism such as serum alkaline phosphatase (ALP),
      bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD), C
      terminal propeptide of type I collagen (CICP), N-telopeptide of type I collagen
      (NTX), and hormonal regulators such as 25-hydroxy vitamin D3 (25Vit D), intact
      parathyroid hormone (i-PTH), and cortisol. RESULTS: The body weight in all the
      age groups was significantly lower at HA as compared to SL values. Prolonged
      residency at HA led to a significant decline in bone strength in terms of SOS,
      both at radius and phalanx. There was a significant increase in circulating Ca
      and ALP levels. Serum i-PTH and 25VitD levels decreased significantly.
      Significant decreases were also observed in CICP and BAP, bone formation markers,
      and serum NTX, DPD/Cr ratio, markers of bone resorption. CONCLUSION: These
      observations suggest that prolonged residency under hypoxic environment is
      associated with a decline in both bone formation and bone resorption markers,
      reflecting a lower bone turnover at HA.

PMID- 24666003
TI  - Muscle power training in the institutionalized frail: a new approach to
      counteracting functional declines and very late-life disability.
AB  - Skeletal muscle power decreases earlier than muscle strength with advancing age
      and is more strongly associated with functional test performance than muscle
      strength in elderly populations. In addition, some studies have shown that
      resistance training designed to improve muscle power output (high speed of
      movement) enhances several functional outcomes in the healthy elderly. Therefore,
      muscle power has emerged as a factor that is also potentially associated with
      functional limitations in frail elderly adults. The purpose of this review was to
      provide recent evidence regarding the association between skeletal muscle power
      and functional capacity in physically frail individuals. Scielo, Science Citation
      Index, MEDLINE, Scopus, Sport Discus and ScienceDirect databases were searched
      from 1990 to 2014. Recently, it has been shown that functional capacity among
      frail elderly adults could be improved by performing resistance training at a
      high speed of movement with a loading stimulus that optimizes muscle power
      output. Routine multicomponent interventions that include muscle power training
      should be prescribed to institutionalized oldest old because such interventions
      improve the overall physical status of frail elderly individuals and prevent
      disability and other adverse outcomes. This result is especially important in
      frail subjects, who urgently need to improve their functional capacities to
      prevent adverse outcomes such as falls, hospitalizations, disability, or even
      death.

PMID- 24666004
TI  - Phytochemical profiles and antimicrobial activity of aromatic Malaysian herb
      extracts against food-borne pathogenic and food spoilage microorganisms.
AB  - Preliminary phytochemical and flavonoid compounds of aqueous and ethanolic
      extracts of 6 aromatic Malaysian herbs were screened and quantified using Reverse
      Phase High Performance Liquid Chromatography (RP-HPLC). The herbal extracts were
      tested for their antimicrobial activity against 10 food-borne pathogenic and food
      spoilage microorganisms using disk diffusion assay. The minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC)/minimum
      fungicidal concentration (MFC) of herbal extracts were determined. In the
      phytochemical screening process, both aqueous and ethanolic extracts of P.
      hydropiper exhibited presence of all 7 tested phytochemical compounds. Among all
      herbal extracts, the aqueous P. hydropiper and E. elatior extracts demonstrated
      the highest antibacterial activity against 7 tested Gram-positive and Gram
      negative bacteria with diameter ranging from 7.0 to 18.5 mm and 6.5 to 19 mm,
      respectively. The MIC values for aqueous and ethanolic extracts ranged from 18.75
      to 175 mg/mL and 0.391 to 200 mg/mL, respectively while the MBC/MFC values for
      aqueous and ethanolic extracts ranged from 25 to 200 mg/mL and 3.125 to 50 mg/mL,
      respectively. Major types of bioactive compounds in aqueous P. hydropiper and E.
      elatior extracts were identified using RP-HPLC instrument. Flavonoids found in
      these plants were epi-catechin, quercetin, and kaempferol. The ability of aqueous
      Persicaria hydropiper (L.) H. Gross and Etlingera elatior (Jack) R.M. Sm.
      extracts to inhibit the growth of bacteria is an indication of its broad spectrum
      antimicrobial potential. Hence these herbal extracts may be used as natural
      preservative to improve the safety and shelf-life of food and pharmaceutical
      products. 

PMID- 24666005
TI  - When should a stent be placed in patients with vascular access
      dysfunction/failure?

PMID- 24666006
TI  - Characterization of a novel HLA-DQB1*05 allele, HLA-DQB1*05:03:09.

PMID- 24666007
TI  - A case of pseudoepitheliomatous hyperplasia to tattoos.

PMID- 24666009
TI  - Synthesis of an Fe rich amorphous structure with a catalytic effect to rapidly
      decolorize Azo dye at room temperature.
AB  - In this article, an amorphous Fe rich amorphous structure designed based on a
      competitive atomic cluster model was synthesized and characterized successfully.
      The constituent zero-valent iron (ZVI) has excellent activity and efficiency for
      decolorization of Orange G (OG) solution at room temperature. The decolorization
      is characterized by UV-vis spectrum and pseudo-first-order kinetics. The X-ray
      Micro fluorescence spectrometer, Inductively Coupled Plasma Optical Emission
      Spectrometry, and Scanning Electron Microscope were employed to trace the ZVI.
      The consumption of ZVI destabilizes the local atomic arrangement and yields the
      phase separation of Fe at the surface and responds to the high activity and the
      catalysis for decolorization. This observation is in accordance with the change
      of k1 0.011 min(-1) to k2 0.047 min(-1), which is supported by the cyclic
      decolorization test. This work provides a new strategy to design multifunctional
      metal materials and indicates their brilliant future in practical applications. 

PMID- 24666008
TI  - Mini-review: Antimicrobial peptides and enzymes as promising candidates to
      functionalize biomaterial surfaces.
AB  - Biomaterial-associated infections remain a serious concern in modern healthcare.
      The development of materials that can resist or prevent bacterial attachment
      constitutes a promising approach to dealing with this problem. Antimicrobial
      peptides (AMPs) and enzymes have been recognized as promising candidates for the
      new generation of antimicrobial surfaces. AMPs have been the focus of great
      interest in recent years owing to a low propensity for developing bacterial
      resistance, broad-spectrum activity, high efficacy at very low concentrations,
      target specificity, and synergistic action with classical antibiotics. Biofilm
      dispersing enzymes have been shown to inhibit biofilm formation, detach
      established biofilm, and increase biofilm susceptibility to other antimicrobials.
      This review critically examines the potential of these protein-like compounds for
      developing antibacterial coatings by reporting their immobilization into
      different substrata using different immobilization strategies.

PMID- 24666010
TI  - Significance of repeat programmed ventricular stimulation at electrophysiology
      study for arrhythmia prediction after acute myocardial infarction.
AB  - BACKGROUND: The prognostic significance of a second programmed ventricular
      stimulation (PVS) at electrophysiology study (EPS), when the first PVS is
      negative for inducible ventricular tachycardia (VT), in patients following
      myocardial infarction (MI) is unknown. METHODS: Consecutive ST-elevation MI
      patients with left ventricular ejection fraction <= 40% following
      revascularization underwent early EPS. An implantable cardioverter defibrillator
      (ICD) was implanted for a positive (inducible monomorphic VT) but not a negative
      (no arrhythmia or inducible ventricular fibrillation [VF]/flutter) EPS. The
      combined primary end point of death or arrhythmia (sudden death, resuscitated
      cardiac arrest, and spontaneous VT/VF) was assessed in EPS-positive patients
      grouped according to if VT was induced on the first PVS application, or the
      second PVS application, when the first was negative. RESULTS: EPS performed a
      median 8 days post-MI in 290 patients was negative in 70% (n = 203) and positive
      in 30% (n = 87). In patients with a positive EPS, VT was induced on the first PVS
      in 67% (n = 58) and the second PVS, after the first was negative, in 33% (n =
      29). Predischarge ICD was implanted in 79 of 87 patients with a positive EPS.
      Three-year primary end point occurred in 20.9 +/- 5.6% and 38.3 +/- 9.7% of
      patients with VT induced by the first and second PVS, respectively (P = 0.042)
      and in 6.3 +/- 1.9% of electrophysiology-negative patients (P < 0.001).
      CONCLUSIONS: In patients with post-MI left ventricular dysfunction, VT can be
      induced in a significant proportion with a second PVS when negative on the first.
      These patients have a similar higher risk of death or arrhythmia compared to
      patients with VT induced on the first PVS.

PMID- 24666011
TI  - Sequential release of autophagy inhibitor and chemotherapeutic drug with
      polymeric delivery system for oral squamous cell carcinoma therapy.
AB  - Autophagy inhibition is emerging as a new paradigm for efficient cancer therapy
      by overcoming multidrug resistance (MDR). Here, we developed an effective
      chemotherapeutic system for oral squamous cell carcinoma (OSCC) based on
      polymeric nanomicelles for codelivery of the anticancer drug doxorubicin (DOX)
      and the autophagy inhibitor LY294002 (LY). The hydrophobic DOX was conjugated
      onto a hydrophilic and pH-responsive hyperbranched polyacylhydrazone (HPAH),
      forming the DOX-conjugated HPAH (HPAH-DOX). Due to its amphiphilicity, HPAH-DOX
      self-assembled into nanomicelles in an aqueous solution and the autophagy
      inhibitor LY could be loaded into the HPAH-DOX micelles. The release of DOX and
      LY from the LY-loaded HPAH-DOX micelles was pH-dependent, whereas LY was released
      significantly faster than DOX at a mildly acidic condition. The in vitro
      evaluation demonstrated that the LY-loaded HPAH-DOX micelles could rapidly enter
      cancer cells and then release LY and DOX in response to an intracellular acidic
      environment. Compared to the HPAH-DOX micelles and the physical mixture of HPAH
      DOX and LY, the LY-loaded HPAH-DOX micelles induced a higher proliferation
      inhibition of tumor cells, illustrating a synergistic effect of LY and DOX. The
      preferentially released LY inhibited the autophagy of tumor cells and made them
      more sensitive to the subsequent liberation of DOX. The polymeric codelivery
      system for programmable release of the chemotherapy drug and the autophagy
      inhibitor provides a new platform for combination of traditional chemotherapy and
      autophagy inhibition. 

PMID- 24666012
TI  - Phase II study of concurrent selective lymph node late course accelerated hyper
      fractionated radiotherapy and pemetrexed and cisplatin for locally advanced
      oesophageal squamous cell carcinoma.
AB  - OBJECTIVE: To determine the clinical efficacy and toxicity of pemetrexed combined
      with low-dose cisplatin (CDDP) concurrent with late-course accelerated
      hyperfractionated (LCAF) intensity-modulated radiation therapy (IMRT) in patients
      with inoperable locally advanced oesophageal squamous cell carcinoma (ESCC).
      METHODS: Patients with locally advanced ESCC (less than or equal to 75 years of
      age, clinical stages IIB-IVA and Karnofsky performance status >=70) were enrolled
      into the study. A target group size of 22 was projected based on the estimation
      that 2-year overall survival (OS) would increase from 20% to 40%. Patients were
      treated with pemetrexed, low-dose CDDP and LCAF IMRT concurrently. The main
      objective of the study was for a 2-year OS, and the secondary objectives were
      progression-free survival (PFS), objective response, locoregional failure rate,
      and acute and late toxicities. RESULTS: 25 patients were recruited from October
      2008 to July 2011. The median OS was 21 months, with 2- and 5-year OS rates of
      44% and 44%, respectively. The median PFS was 18.2 months. The objective response
      rate was 96% (24/25), with 11 complete responses and 13 partial responses. The
      locoregional failure rate was 16%. Grades 4 and 5 acute toxicity rates were 8%
      and 4%, respectively, while no Grade 3 or greater late toxicity was observed.
      CONCLUSION: The findings of this Phase II study indicated that the therapeutic
      regimen appears to achieve an excellent response rate and favourable survival for
      locally advanced ESCC. However, the severe acute side effects should be
      considered cautiously in further studies. ADVANCES IN KNOWLEDGE: To our
      knowledge, this is the first study that introduced pemetrexed and low-dose CDDP
      combined with LCAF IMRT to treat locally advanced ESCC. The 5-year OS rate was as
      high as 44%, which was more favourable than other studies.

PMID- 24666013
TI  - Migration of Ti from nano-TiO2-polyethylene composite packaging into food
      simulants.
AB  - An analytical method based on ICP-MS was developed for the determination of Ti in
      food simulants (3% (w/v) aqueous acetic acid and 50% (v/v) aqueous ethanol). The
      method was used to determine the migration of Ti from nano-TiO2-PE films used for
      food packaging into food simulants under different temperature and migration time
      conditions. The maximum migration amounts into 3% (w/v) aqueous acetic acid were
      1.4 +/- 0.02, 6.3 +/- 0.5 and 12.1 +/- 0.2 MUg kg(-1) at 25, 70 and 100 degrees
      C, respectively, while into 50% (v/v) aqueous ethanol, the maximum migration
      amounts were 0.5 +/- 0.1, 0.6 +/- 0.03 and 2.1 +/- 0.1 MUg kg(-1) at 25, 70 and
      100 degrees C, respectively. Increasing the additive content in the film promoted
      migration of nanoparticles. The results indicated that the migration of
      nanoparticles might occur via dissolution from the surface and cut edges of the
      solid phase (film) into the liquid phase (food simulant).

PMID- 24666014
TI  - Epidemiology of headache disorders in the Asia-pacific region.
AB  - Headache disorder is a major public health issue and is a great burden for the
      person, the health care system, and society. This article reviews epidemiological
      surveys of primary headache disorders including migraine and tension-type
      headache (TTH) among adults in the Asia-Pacific region using the International
      Classification of Headache Disorders (ICHD), first or second edition. Chronic
      daily headache (CDH), which is not an official diagnosis in the ICHD, was also
      reviewed. In the Asia-Pacific region, the median (range) 1-year prevalence of
      primary headache disorders was 9.1% (1.5-22.8%) for migraine, 16.2% (10.8-33.8%)
      for TTH, and 2.9% (1.0-3.9%) for CDH. The 1-year prevalence of migraine and TTH
      were rather consistent; however, the extremes in the 1-year prevalence of
      migraine in earlier studies from Hong Kong (1.5%) and South Korea (22.3%) were
      not repeated in later surveys (Hong Kong: 12.5%; South Korea: 6%). According to
      the United Nations, the estimated population of the Asia-Pacific region was 3.85
      billion in 2010, equaling to headache suffers of 350 million patients with
      migraine, 624 million with TTH, and 112 million with CDH; many remain to be
      treated. The prevalence of headache disorders has remained stable over the last 2
      decades in this region, where the diversity of geography, race, and development
      is wide. Thus, the pursuit of better headache care in this region might be our
      next challenge. 

PMID- 24666015
TI  - Does gestational diabetes history increase epicardial fat and carotid intima
      media thickness?
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is defined as glucose intolerance
      that has begun during pregnancy. Recent studies have proven that development of
      atherosclerosis may be established in this population even without presence of
      type 2 diabetes. For assessment of atherosclerosis, epicardial fat thickness
      (EFT) is recently being used as a surrogate marker. In this study, we aimed to
      prove that women with GDM history are more inclined to have higher EFT levels
      than women without GDM history. METHODS: Sixty-two patients with previous GDM and
      33 age- and sex-matched controls were allocated. Epicardial fat thicknesses of
      the subjects were measured with transthorasic echocardiography and carotid intima
      media thickness (c-IMT) was measured with ultrasound. Insulin resistance (IR) of
      each subject was assessed with Homeostasis model of assessment-insulin resistance
      (HOMA-IR). RESULTS: Carotid IMT and EFT were significantly higher in previous GDM
      group than controls. Serum gamma-glutamyl transferase (GGT), uric acid, and high
      sensitivity C-reactive protein (hs-CRP) levels were also found significantly
      higher in the patients with previous GDM as compared to the controls. We observed
      that carotid IMT (beta = 310, P = 0.003), total cholesterol (beta = 315, P =
      0.002), BMI (beta = 308, P = 0.002), HbA1c (beta = 227, P = 0.018), and HOMA-IR
      (beta = 184, P = 0.049) were independently correlated with EFT. CONCLUSIONS:
      Although the number of patients included in this study is limited, high EFT
      results may indicate presence of atherosclerosis in women with previous GDM.

PMID- 24666016
TI  - Should sleep quality be part of the Lake Louise Acute Mountain Sickness Score?

PMID- 24666017
TI  - Lentiviral-mediated expression of SATB2 promotes osteogenic differentiation of
      bone marrow stromal cells in vitro and in vivo.
AB  - Special AT-rich sequence-binding protein 2 (SATB2 ) acts as a potent
      transcription factor to promote osteoblast differentiation and bone regeneration.
      In this study, we first used lentiviral-mediated gene transfer of Satb2 into
      mouse bone marrow stromal cells (BMSCs) and investigated the capacity of SATB2
      overexpression to promote osteogenic differentiation in vitro and in vivo. We
      found that LV-Satb2 -transduced BMSCs produced SATB2 protein and underwent rapid
      and marked osteogenic differentiation, as demonstrated by increased expression of
      osteoblastic genes, including runt-related transcription factor 2 (Runx2),
      transcription factor Sp7 (Sp7), activating transcription factor 4 (Atf4), and
      bone sialoprotein (Bsp), and increased alkaline phosphatase activity and Alizarin
      Red S staining. To analyze the induction of bone formation in vivo, LV-Satb2
      transduced BMSCs were implanted into the hindlimbs of syngeneic mice, with beta
      tricalcium phosphate as the scaffolding material. Four weeks after implantation,
      transduction with LV-Satb2 had greatly enhanced the formation of new bone. These
      data demonstrated the capacity of lentiviral-mediated SATB2 to promote the
      osteogenic differentiation of BMSCs in vitro and to enhance bone formation
      through a tissue-engineering technique that may be useful in bone-regenerative
      medicine.

PMID- 24666018
TI  - Use of methodological tools for assessing the quality of studies in
      periodontology and implant dentistry: a systematic review.
AB  - OBJECTIVE: To evaluate the methodological approaches used to assess the quality
      of studies included in systematic reviews (SRs) in periodontology and implant
      dentistry. MATERIALS & METHODS: Two electronic databases (PubMed and Cochrane
      Database of Systematic Reviews) were searched independently to identify SRs
      examining interventions published through 2 September 2013. The reference lists
      of included SRs and records of 10 specialty dental journals were searched
      manually. Methodological approaches were assessed using seven criteria based on
      the Cochrane Handbook for Systematic Reviews of Interventions. Temporal trends in
      methodological quality were also explored. RESULTS: Of the 159 SRs with meta
      analyses included in the analysis, 44 (28%) reported the use of domain-based
      tools, 15 (9%) reported the use of checklists and 7 (4%) reported the use of
      scales. Forty-two (26%) SRs reported use of more than one tool. Criteria were met
      heterogeneously; authors of 15 (9%) publications incorporated the quality of
      evidence of primary studies into SRs, whereas 69% of SRs reported methodological
      approaches in the Materials/Methods section. Reporting of four criteria was
      significantly better in recent (2010-2013) than in previous publications.
      CONCLUSION: The analysis identified several methodological limitations of
      approaches used to assess evidence in studies included in SRs in periodontology
      and implant dentistry.

PMID- 24666019
TI  - Emerging role of probiotics and antimicrobials in the management of irritable
      bowel syndrome.
AB  - OBJECTIVE: To review the potential role of probiotics and antimicrobials for
      management of functional bowel disorders (FBDs), with a focus on irritable bowel
      syndrome (IBS). RESEARCH DESIGN AND METHODS: Relevant adult data were identified
      via PubMed, with additional references obtained by reviewing bibliographies from
      selected articles. RESULTS: Probiotic treatment involves colonizing the
      intestines with beneficial microorganisms, whereas antimicrobial therapy involves
      modulation of the bacterial load and/or host response. A meta-analysis reported
      that all probiotic species evaluated improved flatulence compared with placebo;
      some, but not all, species improved abdominal pain and abdominal
      bloating/distension; and no species evaluated improved stool frequency or
      consistency, straining during stool evacuation, sense of incomplete evacuation,
      or fecal urgency. Two additional meta-analyses reported that probiotics
      significantly improved overall IBS symptoms. Individual studies have demonstrated
      potential benefits of probiotics for functional constipation symptoms. The
      nonsystemic antimicrobials neomycin and rifaximin have been evaluated in patients
      with IBS and other FBDs. Neomycin may improve global IBS symptoms and provide
      bowel normalization versus placebo, but the risk of ototoxicity and the
      development of clinically relevant bacterial resistance may limit its use for
      recurrent symptoms. In phase 3 randomized studies, rifaximin-treated patients
      were significantly more likely than placebo-treated patients to achieve adequate
      relief of global IBS symptoms and abdominal bloating. Although preliminary data
      suggest that development of clinically relevant bacterial resistance is unlikely
      with rifaximin, prospective data are needed, and a phase 3 study is ongoing.
      Limitations of evidence for probiotics include small populations analyzed and
      lack of clarity in optimal dosing regimen; antimicrobial evidence would benefit
      from better understanding of the effects of repeated treatment in patients with
      IBS. CONCLUSIONS: Probiotics and nonsystemic antibiotics have a place in IBS
      management. Additional studies are needed to establish optimal regimens and
      identify subgroups of patients most likely to benefit from these therapies.

PMID- 24666021
TI  - Use of eculizumab in refractory gemcitabine-induced thrombotic microangiopathy.

PMID- 24666022
TI  - Biomimetic nucleation of hydroxyapatite crystals mediated by Antheraea pernyi
      silk sericin promotes osteogenic differentiation of human bone marrow derived
      mesenchymal stem cells.
AB  - Biomacromolecules have been used as templates to grow hydroxyapatite crystals
      (HAps) by biomineralization to fabricate mineralized materials for potential
      application in bone tissue engineering. Silk sericin is a protein with features
      desirable as a biomaterial, such as increased hydrophilicity and biodegradation.
      Mineralization of the silk sericin from Antheraea pernyi (A. pernyi) silkworm has
      rarely been reported. Here, for the first time, nucleation of HAps on A. pernyi
      silk sericin (AS) was attempted through a wet precipitation method and
      consequently the cell viability and osteogenic differentiation of BMSCs on
      mineralized AS were investigated. It was found that AS mediated the nucleation of
      HAps in the form of nanoneedles while self-assembling into beta-sheet
      conformation, leading to the formation of a biomineralized protein based
      biomaterial. The cell viability assay of BMSCs showed that the mineralization of
      AS stimulated cell adhesion and proliferation, showing that the resultant AS
      biomaterial is biocompatible. The differentiation assay confirmed that the
      mineralized AS significantly promoted the osteogenic differentiation of BMSCs
      when compared to nonmineralized AS as well as other types of sericin (B. mori
      sericin), suggesting that the resultant mineralized AS biomaterial has potential
      in promoting bone formation. This result represented the first work proving the
      osteogenic differentiation of BMSCs directed by silk sericin. Therefore, the
      biomineralization of A. pernyi silk sericin coupled with seeding BMSCs on the
      resultant mineralized biomaterials is a useful strategy to develop the potential
      application of this unexplored silk sericin in the field of bone tissue
      engineering. This study lays the foundation for the use of A. pernyi silk sericin
      as a potential scaffold for tissue engineering. 

PMID- 24666023
TI  - Chamaerops humilis L. var. argentea Andre date palm seed oil: a potential
      dietetic plant product.
AB  - Chamaerops humilis L. var. argentea Andre (C. humilis) date palm seeds are an
      underutilized source of vegetable oil, and no studies describing their
      physicochemical characteristics to indicate the potential uses of this seed or
      seed oil have been reported. The oil content of the seeds is about 10%, mainly
      composed of oleic acid (38.71%), lauric acid (21.27%), linoleic acid (15.15%),
      palmitic acid (9.96%), and stearic acid (7.17%). The tocol (tocopherols and
      tocotrienols) content is 74 mg/100 g, with delta-tocotrienol as the major
      contributor (31.91%), followed by alpha-tocotrienol (29.37%), gamma-tocopherol
      (20.16%), and gamma-tocotrienol (11.86%). Furthermore, this oil shows high
      thermal stability. The differential scanning calorimetery curves revealed that
      the melting and crystallization points are 9.33  degrees C and -15.23  degrees C,
      respectively. 

PMID- 24666025
TI  - Effects of ventilation and catheter position on catheter movement on the
      tricuspid annulus during ablation in children.
AB  - INTRODUCTION: There are little data on the effect of catheter position and
      mechanical ventilation on ablation catheter stability during electrophysiology
      study in children. We sought to determine the magnitude of catheter movement with
      mechanical ventilation, the effect of ventilation maneuvers on catheter movement,
      and to compare the degree of movement observed between the right lateral (RL) and
      right posteroseptal (RPS) regions. METHODS: From June 2012 to June 2013, patients
      <= 21 years of age undergoing ablation for supraventricular tachycardia with
      CARTO(r) 3 (Biosense Webster, Diamond Bar, CA, USA) were included. During mapping
      the ablation catheter was placed in the RPS and RL regions and the magnitude of
      catheter movement (mm) was measured using CARTO(r) 3. Measurements were made
      during routine ventilation and with a maximal inspiration maneuver between end
      expiration (ENDEX) and peak-inspiration (PEAKINS). RESULTS: Twenty-one patients
      were included: 12 males (57%), age 13 +/- 3 years, weight 55 +/- 14 kg.
      Indications for ablation were: 10 Wolff-Parkinson-White, seven atrioventricular
      node re-entry tachycardia, four concealed accessory pathway. Mechanical
      ventilation was used in all cases. The magnitude of catheter movement was 3.6 +/-
      1.7 mm with routine ventilation and 6.2 +/- 4.1 mm between ENDEX and PEAKINS (P
      <= 0.01). Catheter movement was greater in the RL compared to the RPS region with
      routine ventilation (RL 4.3 +/- 1.6 vs RPS 3.0 +/- 1.5; P < 0.01) and between
      ENDEX and PEAKINS (RL 8.3 +/- 4.7 vs RPS 4.0 +/- 1.7; P < 0.01). CONCLUSIONS:
      Ventilation and catheter position both have significant impact on the degree of
      catheter movement during ablation. Movement was greatest in the RL position. This
      may partially explain the lower success rates of ablation in the RL region.

PMID- 24666024
TI  - T helper type 17 pathway suppression by appendicitis and appendectomy protects
      against colitis.
AB  - Appendicitis followed by appendectomy (AA) at a young age protects against
      inflammatory bowel disease (IBD). We wanted to characterize the role of the T
      helper type 17 (Th17) system involved in this protective effect. AA was performed
      on 5-week-old male BALB/c mice and distal-colon samples were harvested. Mice with
      two laparotomies each served as sham-sham (SS) controls. RNA was extracted from
      four individual colonic samples per group (AA and SS groups) and each sample
      microarray-analysed and reverse transcription-polymerase chain reaction (RT-PCR)
      validated. Gene-set enrichment analysis (GSEA) showed that the Th17 recruitment
      factor gene CCL20 was significantly suppressed at both 3 days post-AA and 28 days
      post-AA. Although Th17 cell development differentiation factor genes TGF-beta2
      and TGF-beta3 were significantly up-regulated 3 days post-AA, GSEA 28 days post
      AA showed that AA down-regulated 29 gene-sets associated with TGF-beta1, TGF
      beta2 and TGF-beta3 in contrast to none up-regulated with any of these genes.
      GSEA showed substantial down-regulation of gene-sets associated with Th17
      lymphocyte recruitment, differentiation, activation and cytokine expression in
      the AA group 28 days post-AA. We conclude that Th17-system cytokines are kept
      under control by AA via down-regulation of proinflammatory CCL20, a rapid down
      regulation of pro-Th17 cell differentiation genes TGF-beta2 and TGF-beta3,
      suppression of RORC-associated gene-sets, increased protective STAT1 expression
      and suppression of 81 'pro-Th17' system gene-sets. AA suppresses the Th17 pathway
      leading to colitis amelioration. Further characterization of Th17-associated
      genes and biological pathways will assist in the development of better
      therapeutic approaches in IBD management. 

PMID- 24666026
TI  - Proteomic analysis of phosphorylation in cancer.
AB  - Constitutive activity of kinases is known to be crucial for a tumor to maintain
      its malignant phenotype, a phenomenon which is often referred to as oncogene
      addiction. The in-depth analysis of aberrant signaling pathways by the analysis
      of protein phosphorylation has become feasible through recent advances in
      proteomics technology. In this article we will review developments in the field
      of phosphoproteomics and its application in cancer research. The most widely used
      technologies for the generic enrichment of phosphopeptides are discussed as well
      as targeted approaches for the analysis of a specific subset of phosphopeptides.
      Validation experiments of phosphorylation sites using targeted mass spectrometry
      are also explained. Finally, we will highlight applications of phosphoproteomic
      technology in cancer research using cell lines and tissue.

PMID- 24666027
TI  - Association of HLA-B27 and ERAP1 with ankylosing spondylitis susceptibility in
      Beijing Han Chinese.
AB  - This study investigated the genetic polymorphisms of HLA-B27, together with
      polymorphisms on endoplasmic reticulum aminopeptidase 1 (ERAP1), and
      susceptibility for ankylosing spondylitis (AS) in the Beijing Han population. A
      case-control study was carried out for 602 AS patient samples and 619 matched
      controls of Han Chinese. HLA-B27 genotyping was performed by polymerase chain
      reaction-sequence specific primers (PCR-SSP), and four ERAP1 SNPs (rs27037,
      rs27980, rs27582, and rs27434) were selected and genotyped on the Sequenom iPlex
      platform (Sequenom, San Diego, CA). Association analysis was performed using the
      likelihood ratio chi(2) test. This study identified four HLA-B27 alleles in
      Beijing Han AS patients, B*27:02, B*27:04, B*27:05, and B*27:07, of which B*27:05
      was the most significant geographical different subtype among AS patients in
      Chinese. Our results confirmed that HLA-B27 was strongly associated with AS
      (P=1.9 * 10(-150) ), and the most strongly associated alleles were B*27:04,
      B*27:05, and B*27:02. Our study also confirmed a weak association between ERAP1
      (rs27434) and AS. We also observed that for HLA-B*27:02 and HLA-B*27:04 positive
      AS patients, rs27434 and rs27582 were associated with AS. In contrast, for HLA
      B27-negative and HLA-B*27:05-positive AS patients, this association was not
      observed. This is the first study to show that both B27 and ERAP1 are AS genetic
      susceptibility genes in Beijing Han. Interactions between ERAP1 and HLA-B*27:02
      and B*27:04 may play an important role in the AS pathogenesis.

PMID- 24666028
TI  - A vanishing left ventricular outflow tract mass: an uncommon manifestation of
      systemic lupus erythematosus.

PMID- 24666029
TI  - Effects of acute systematic hypoxia on human urinary metabolites using LC-MS
      based metabolomics.
AB  - AIMS: The metabolic variability and response to acute systematic hypoxia have
      been characterized by the high resolution of liquid chromatography/time-of
      flight/mass spectrometry (LC-TOF/MS) in this study. Specifically, we compared the
      urinary metabolic profiles of six healthy sedentary men under normoxia (21% O2)
      with acute systematic hypoxic conditions of 12% (equivalent to about 4500 m in
      altitude) and 15% O2 (equivalent to about 3000 m in altitude) for 2 h in a
      normobaric hypoxia chamber. RESULTS: A clear separation of dose-dependent
      responses was visualized by Partial Least Squares Discriminant Analysis (PLS-DA)
      between normoxic and hypoxic conditions. Over one thousand features were found in
      this study, about 10% of which showed significant change from hypoxia treatment
      and 26 metabolites were identified; however, there is great variability in
      metabolite concentrations among the 6 subjects, which reflects the diversity of
      human systems. Within the variability, we found that 1-methyladenosine and 5
      methylthioadenosine are conspicuously upregulated; on the other hand, 3
      inodoleacetic acid and L-glutamic acid were downregulated. CONCLUSION: The
      increase in purine metabolic products (uric acid, xanthine, and hypoxathine)
      results from hypoxia; this increase can be used as a marker for the hypoxic
      condition. 1-Methyladenosine was also highly upregulated from MH to SH and may be
      a very sensitive biomarker that reflects cellular hypoxia, due to its potential
      connection to HIF-1. The increase of free carnitine and acetyl carnitines, on the
      other hand, signals a change in the pathway of energy, or lipid, metabolism.

PMID- 24666030
TI  - Effects of tourniquet ischaemia and time safety in toe surgery.

PMID- 24666031
TI  - Alkyl groups fold to fit within a water-soluble cavitand.
AB  - We report here a widened, deep cavitand host that binds hydrophobic and
      amphiphilic guests in D2O. Small alkanes (C6 to C11) are bound in compressed
      conformations and tumble rapidly within the space. Longer n-alkanes (C13 to C14),
      n-alcohols, and alpha,omega-diols are taken up in folded conformations. The
      guests' termini are exposed to solvent while atoms near the alkane's center are
      buried and protected. The cavitand acts as a concave template that pushes
      terminal atoms of the guest closer together. The unexpected binding modes are
      interpreted in terms of the size and shape of the space accessible in the new
      cavitand. 

PMID- 24666032
TI  - Effect of isomerism and chain length on electronic structure, photophysics, and
      sensitizer efficiency in quadrupolar (donor)2-acceptor systems for application in
      dye-sensitized solar cells.
AB  - We report on quadrupolar (donor)2-acceptor sensitizers for dye-sensitized solar
      cells (DSSCs). The acceptor units are based on dithieno[2,3-a:3',2'-c]phenazine
      and dithieno[3,2-a:2',3'-c]phenazine coupled to thiophene donors. The
      optoelectronic and photophysical properties of two sets of isomers reveal a rigid
      structure for linear isomers and an efficient nonradiative decay for branched
      isomers. These sensitizers were integrated into DSSCs, and the quadrupolar
      structure is an operational design, as the IPCE reached up to 38% from 400 nm to
      600 nm. The lengthening of the donor chain increases the efficiency,
      demonstrating the appeal of these oligomeric dyes for DSSCs. 

PMID- 24666033
TI  - Replication of migraine GWAS susceptibility loci in Chinese Han population.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have identified 3
      genetic variants that are strongly associated with migraine in Europeans. The
      effect of these risk variants in other populations is unknown. To further
      replicate the GWAS findings, we investigated the 3 variants rs2651899 (1p36.32,
      PRDM16), rs10166942 (2q37.1, TRPM8), and rs11172113 (12q13.3, LRP1) for their
      association with migraine in the Chinese Han population. METHODS: We performed a
      case-control association study. Genomic DNA was collected from 608 unrelated
      individuals, including 304 migraineurs (41 migraine with aura and 263 migraine
      without aura) and 304 healthy controls. Genotyping of single nucleotide
      polymorphisms (SNPs) was performed by ligase detection reaction method. RESULTS:
      We identified the minor allele of rs2651899 located in PRDM16 to be associated
      with migraine (P = .005, odds ratio = 1.382, 95% confidence interval = 1.100
      1.736), the association remain significant after Bonferroni correction. For the
      other 2 SNPs (rs10166942 and rs11172113), no statistically significant
      differences were observed in the allele/genotype frequencies between cases and
      controls. None of the 3 SNP was associated with specific migraine features.
      CONCLUSION: Our study confirmed the association of PRDM16 to migraine
      susceptibility in the Chinese Han population. The results also indicated that
      replication studies of previous GWAS findings across populations is of importance
      to validate these associations and to gain a better understanding of migraine
      susceptibility of potential genetic heterogeneity between populations. Further
      work is necessary to understand the functional mechanisms underlying these
      variants identified by GWAS.

PMID- 24666034
TI  - Should nephrology training programs continue to train fellows in the placement of
      temporary hemodialysis catheters?

PMID- 24666035
TI  - Nontoxic piperamides and their synthetic analogues as novel antifouling reagents.
AB  - Bioassay-guided isolation of an acetone extract from a terrestrial plant Piper
      betle produced four known piperamides with potent antifouling (AF) activities, as
      evidenced by inhibition of settlement of barnacle cypris larvae. The AF
      activities of the four piperamides and 15 synthesized analogues were compared and
      their structure-activity relationships were probed. Among the compounds,
      piperoleine B and 1-[1-oxo-7-(3',4'-methylenedioxyphenyl)-6E-heptenyl]-piperidine
      (MPHP) showed strong activity against settlement of cyprids of the barnacle
      Balanus amphitrite, having EC50 values of 1.1 +/- 0.3 and 0.5 +/- 0.2 MUg ml(-1),
      respectively. No toxicity against zebra fish was observed following incubation
      with these two compounds. Besides being non-toxic, 91% of piperoleine B-treated
      cyprids and 84% of MPHP-treated cyprids at a concentration of 100 MUM completed
      normal metamorphosis in recovery bioassays, indicating that the anti-settlement
      effect of these two compounds was reversible. Hydrolysis and photolysis
      experiments indicated that MPHP could be decomposed in the marine environment. It
      is concluded that piperamides are promising compounds for use in marine AF
      coatings.

PMID- 24666036
TI  - Organic solar cells based on three-dimensionally percolated polythiophene
      nanowires with enhanced charge transport.
AB  - The influence of micrometer-scale poly(3-hexylthiophene) (P3HT) nanowires (NWs)
      and P3HT nanocrystals (NCs) on the photocurrent generation in photoactive layers
      having various thickness values was investigated. Self-organizing P3HT NWs were
      fabricated using a marginal solvent. Transmission electron microtomography was
      used to characterize the vertical and horizontal crystalline morphologies of the
      NWs and their intergrain percolation networks in the active layers. The
      interpenetrating P3HT NWs promoted charge transport, as demonstrated by the
      enhanced percolation probability and the reduction in bimolecular recombination.
      The photovoltaic performances were enhanced as the photoactive layer thickness
      increased because internal quantum efficiencies of the solar devices prepared
      with active layers having NWs were maintained with varying thicknesses,
      suggesting that the conversion of absorbed photons into a photocurrent proceeded
      efficiently. By contrast, the photovoltaic performances of an NC-only photoactive
      layer were reduced by the increase in thickness due to its poorly developed
      percolation pathways. The incorporation of P3HT NWs into the P3HT:indene-C60
      bisadduct photoactive layers yielded a device power conversion efficiency (PCE)
      of 5.42%, and the photocurrent did not decrease significantly up to a thickness
      of 600 nm, resulting in a PCE of 3.75%, 70% of the maximum PCE of 5.42%. 

PMID- 24666037
TI  - NRLiSt BDB, the manually curated nuclear receptors ligands and structures
      benchmarking database.
AB  - Nuclear receptors (NRs) constitute an important class of drug targets. We created
      the most exhaustive NR-focused benchmarking database to date, the NRLiSt BDB (NRs
      ligands and structures benchmarking database). The 9905 compounds and 339
      structures of the NRLiSt BDB are ready for structure-based and ligand-based
      virtual screening. In the present study, we detail the protocol used to generate
      the NRLiSt BDB and its features. We also give some examples of the errors that we
      found in ChEMBL that convinced us to manually review all original papers. Since
      extensive and manually curated experimental data about NR ligands and structures
      are provided in the NRLiSt BDB, it should become a powerful tool to assess the
      performance of virtual screening methods on NRs, to assist the understanding of
      NR's function and modulation, and to support the discovery of new drugs targeting
      NRs. NRLiSt BDB is freely available online at http://nrlist.drugdesign.fr . 

PMID- 24666039
TI  - The DH is talking utter nonsense about pay.
AB  - 'Union leaders talk tough on pay' is a headline that could have been written
      thousands of times over the past 100 years, but rarely have nurses'
      representatives been so furious as they are now. Two weeks on from the decision
      to withhold a 1 per cent pay award from most NHS nursing staff in England and
      Wales, and tempers are continuing to flare. 

PMID- 24666038
TI  - mCare: using secure mobile technology to support soldier reintegration and
      rehabilitation.
AB  - BACKGROUND: The U.S. Army Medical Department conducted a pilot mobile health
      project to determine the requirements for coordination of care for "Wounded
      Warriors" using mobile messaging. The primary objective was to determine if a
      secure mobile health (mhealth) intervention provided to geographically dispersed
      patients would improve contact rates and positively impact the military
      healthcare system. METHODS AND MATERIALS: Over 21 months, volunteers enrolled in
      a Health Insurance Portability and Accountability Act-compliant, secure mobile
      messaging initiative called mCare. The study included males and females, 18-61
      years old, with a minimum of 60 days of outpatient recovery. Volunteers were
      required to have a compatible phone. The mhealth intervention included
      appointment reminders, health and wellness tips, announcements, and other
      relevant information to this population exchanged between care teams and
      patients. RESULTS: Provider respondents reported that 85% would refer patients to
      mCare, and 56% noted improvement in appointment attendance (n=90). Patient
      responses also revealed high acceptability of mCare and refined the frequency and
      delivery times (n=114). The pilot project resulted in over 84,000 outbound
      messages and improved contact rates by 176%. CONCLUSIONS: The mCare pilot project
      demonstrated the feasibility and administrative effectiveness of a scalable
      mhealth application using secure mobile messaging and information exchanges,
      including personalized patient education.

PMID- 24666040
TI  - Furious nurses protest against refusal to grant them a pay rise.
AB  - 'Demoralised' nurses have been making their voice heard in pickets after the
      majority of nursing staff in England were denied a pay rise. 

PMID- 24666042
TI  - Conviction for ill-treatment may deter whistleblowing.
AB  - Proposals to prosecute nurses who wilfully neglect patients could discourage
      staff from raising concerns about poor care, nurse leaders in Wales were warned. 

PMID- 24666044
TI  - Student who exposed cruelty urges others to act.
AB  - A former nursing student whose evidence helped to convict three healthcare
      support workers of abusing older patients has urged other students not to
      hesitate in speaking up if they witness patients being mistreated. 

PMID- 24666045
TI  - Call for more nurses to join military reservists and fill vital caring role.
AB  - The armed forces need more nurse reservists to cope with future conflicts and the
      changing face of the British military, the RCN has warned. 

PMID- 24666051
TI  - Support teams can help patients arriving at hospitals malnourished.
AB  - Almost one third of adults in the UK are malnourished on admission to hospital, a
      report states. 

PMID- 24666054
TI  - Greater attention needed for end of life and palliative care.
AB  - Hospitals must get better at identifying patients who are in their last year of
      life so they can provide appropriate care, according to the authors of a new
      Scottish study of hospital inpatients. 

PMID- 24666055
TI  - Don't rely on regulation - think for yourself, standards chief tells staff.
AB  - Regulation is not the key to assuring that the best nurses are working in the
      NHS, a patient safety and quality conference heard last week. 

PMID- 24666057
TI  - Feeling the registration fee squeeze.
AB  - As the Nursing and Midwifery Council decides this week whether to consult on
      increasing the registration fee to L120, opposition to the move grows. 

PMID- 24666058
TI  - Voting yes could help scots shake off shackles.

PMID- 24666064
TI  - Psychosis and schizophrenia.
AB  - Essential facts Psychosis and schizophrenia (the latter is often described as a
      psychotic disorder) are mental health conditions in which a person's perception,
      thoughts, mood and behaviour are significantly altered. Over a lifetime, about
      one in 100 people will experience the symptoms, according to the National
      Institute for Health and Care Excellence (NICE). 

PMID- 24666065
TI  - Keeping fiction true to life.
AB  - Nurse Teresa Lynch spent a day on the set of the BBC television drama Silk,
      advising the programme makers on the portrayal of character with advanced
      prostate cancer. She ensured equipment and procedures were accurate, and
      encouraged the script writer to make the storyline more hopefull.

PMID- 24666066
TI  - In the wake of the Francis shock wave.
AB  - the Francis into failures of care at Mid Staffordshire NHS Foundation Trust sent
      a shock wave through the NHS. A year after the final report was published,
      patient safety and quality of care are now higher priorities for trusts. But
      financial realities still hinder full implementation of the recommendations.

PMID- 24666069
TI  - Voices - Government action on pay in England beggars belief, says Peter Carter.
AB  - The government's decision to reject the recommendation of the independent pay
      review body and deny a cost of living increase to NHS staff in England is
      infuriating, ill-advised, and immoral. 

PMID- 24666085
TI  - Using humour to enhance the nurse-patient relationship.
AB  - The appropriate use of humour is a valuable asset in nursing practice. Used daily
      in interactions with patients, humour can help to develop the therapeutic
      relationship and build resilience. This article discusses how humour can promote
      physiological and psychological wellbeing, while reducing stress and anxiety.
      Recommendations for including humour in patient care are outlined. 

PMID- 24666086
TI  - Management of patients with empyema.
AB  - Empyema is the term used to describe an accumulation of pus in a body cavity such
      as the pleural space as a result of bacterial infection. The condition is serious
      because it is difficult for the immune system to resolve infection in this area.
      Empyema can be avoided by the use of appropriate antibiotic therapy and good
      aseptic technique when dealing with any situation that breaches the chest wall.
      Treatment of this condition may be medical but if the condition does not resolve,
      surgical intervention is required. The nursing role involves providing support,
      education and long-term management for patients with empyema. 

PMID- 24666087
TI  - Fever and feverish illness in children under five years.
AB  - This article discusses the causes and management of fever in children. In line
      with guidance from the National Institute for Health and Care Excellence, it
      explores the importance of identifying children at risk of serious illness and
      those that can be managed safely at home. The article also identifies the skills
      and knowledge required by paediatric and general nurses working with children,
      alongside the need to offer parents guidance on antipyretics and how to care for
      their child at home. 

PMID- 24666088
TI  - Parenteral nutrition.
AB  - Parenteral nutrition is a method of administering nutrition and hydration
      intravenously. Usually, nutrients are absorbed from the different foods we
      consume via the action of enzymes in the gastrointestinal tract. 

PMID- 24666089
TI  - Why we need dementia training.
AB  - The number of people with dementia is forecast to double from 800,000 over the
      next 20 years. Currently, up to half of all patients in acute medical wards are
      said to be affected by dementia or an associated condition. The latest figures on
      prevalence in care homes indicate that about 90 per cent of residents have
      dementia. 

PMID- 24666090
TI  - Transatlantic ticket to work.
AB  - While European Union (EU) trade agreement negotiations effectively make it easier
      for British nurses to obtain American or Canadian licences to practise, progress
      could be hindered by fragmented nursing regulations in North America. 

PMID- 24666092
TI  - A vital part of the team Erin Dean looks ahead at training for healthcare
      assistants.
AB  - Healthcare assistants (HCAs) in England are to receive improved and standardised
      training. While this will be a major change for the HCA workforce, it will also
      have a significant impact for the nurses who work with them. 

PMID- 24666093
TI  - Student life - duty of care or carefree?
AB  - Undergraduate nursing programmes differ from most other higher education degrees.
      In addition to the expectation that students will meet the required academic
      standard, there is a higher expectation that they will learn to adopt the Nursing
      and Midwifery Council (NMC) code of conduct in their practice and their
      professional lives generally. 

PMID- 24666094
TI  - Clinical analysis and prognostic significance of haemophagocytic
      lymphohistiocytosis-associated anaplastic large cell lymphoma in children.
AB  - Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children
      treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence,
      the clinical and histological characteristics and the prognosis of HLH associated
      ALCL. The medical, biological, cytological and histological data of patients
      treated for ALK-positive ALCL in the paediatric department of a single
      institution between 1975 and 2008 were analysed and assessed for HLH according to
      diagnosis criteria of the Histiocyte Society. Data concerning a series of 50
      consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in
      12% of the patients. Lung involvement was significantly more frequent in HLH
      associated ALCL patients than in the group without HLH (P = 0.004), as well as
      central nervous system (CNS) and bone marrow involvement (P = 0.001 and P = 0.007
      respectively). The histological subtype in children with HLH-associated ALCL did
      not differ from that of the group without HLH. There was no significant
      difference between the two groups in 5-year EFS and OS (P = 0.91 and P > 0.99
      respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high
      incidence of visceral, CNS and bone marrow involvement, HLH does not seem to
      exert a significant impact on outcome in children treated for ALCL.

PMID- 24666096
TI  - Hemisphere Preference Test: psychometric properties and relations with academic
      performance among adolescents.
AB  - The present study explored, in adolescents, the dimensionality (factorial
      structure), reliability (internal consistency and test-retest stability) and
      predictive validity (in relation with academic grades) of the Hemispheric
      Preference Test (HPT), a widely used self-report index of thinking styles among
      adults. A sample of 990 Spanish adolescents aged 10-14 completed HPT and reported
      their academic grades. Results indicated a two-factor structure for HPT that can
      be interpreted in terms of left- and right-Hemisphere Preference (HP). The two
      factor structure was clearer in boys compared to girls. The internal consistency
      and test-retest at 6 and 12 months were satisfactory. Left-HP scores decreased
      with age whereas girls obtained a higher mean score on right-HP sub-scale.
      Finally, Left-HP accounted for a significant variance percentage on academic
      grades after controlling for age and sex. Results suggested that Spanish version
      of the HPT was effective and reliable among adolescents. 

PMID- 24666095
TI  - Applying quality assurance in real time to compliant long-term periodontal
      maintenance patients utilizing cost-effectiveness and cost utility.
AB  - BACKGROUND: Little work has been done on quality assurance of long-term
      maintenance of periodontal therapy MATERIALS/METHODS: A quality assurance model
      was applied to 80 patients (50 females, 30 males) with an average age of 64.3
      years (SD. 8.83, range 45-91) and with 21.6 (SD. 2.65, range 16-26) maintenance
      years. The main elements were patients' expectations, objectives and patient
      based outcomes, human and financial costs and treatment deviations. For cost
      effectiveness, this group was compared with a control group of 25 patients with
      an average of 9.96 years not complying with maintenance therapy. RESULTS: The
      patients' main expectations and reasons for seeking treatment were to save teeth
      and a desire for better oral health. The patients had a total tooth-year loss of
      3.3%. 81.3% reported improved oral health. Total treatment discounted cost was
      ?5842. The cost of buying an extra tooth year was ?20.2. Patients reported
      anxiety of 4.6 (SD10.5, range 0-47) and discomfort of 11.8 (SD13.2 range 0-70)
      for the maintenance visits on the Visual Analogue Scale (VAS). Treatment
      deviations showed 3.8% extreme downhill patients, 6.3% with poor oral hygiene,
      3.8% reported a worsening of their oral health, 3.8% had high anxiety whereas
      5.0% experienced a high level of discomfort. CONCLUSION: It is possible to apply
      a number of elements of a quality assurance measure to a patient population of
      compliant maintenance patients in real time. The results obtained compare well
      with previous internal and external studies. This model should be useful to
      patients and practitioners as well as for larger population-based studies.

PMID- 24666097
TI  - Genipin-cross-linked layer-by-layer assemblies: biocompatible microenvironments
      to direct bone cell fate.
AB  - The design of biomimetic coatings capable of improving the osseointegration of
      bone biomaterials is a current challenge in the field of bone repair. Toward this
      end, layer-by-layer (LbL) films composed of natural components are suitable
      candidates. Chondroitin sulfate A (CSA), a natural glycosaminoglycan (GAG), was
      used as the polyanionic component because it promotes osteoblast maturation in
      vivo. In their native state, GAG-containing LbL films are generally cytophobic
      because of their low stiffness. To stiffen our CSA-based LbL films, genipin (GnP)
      was used as a natural cross-linking agent, which is much less cytotoxic than
      conventional chemical cross-linkers. GnP-cross-linked films display an original
      combination of microscale topography and tunable mechanical properties.
      Structural characterization was partly based on a novel donor/acceptor Forster
      resonance energy transfer (FRET) couple, namely, FITC/GnP, which is a promising
      approach for further inspection of any GnP-cross-linked system. GnP-cross-linked
      films significantly promote adhesion, proliferation, and early and late
      differentiation of preosteoblasts. 

PMID- 24666098
TI  - Optimization of human mtDNA control region sequencing for forensic applications.
AB  - Sequencing mitochondrial DNA hypervariable regions I and II (HVI and HVII) is
      useful in forensic missing person and unidentified remains cases. Improvements in
      ease and sensitivity of testing will yield results from more samples in a timely
      fashion. Routinely, amplification of HVI and HVII is followed by Sanger
      sequencing using the BigDye((r)) Terminator v3.1 Cycle Sequencing kit (Applied
      Biosystems) using 4 MUL of ready reaction mix (RRM). Each sequencing reaction is
      then purified through column filtration before capillary electrophoresis. Using
      lower amounts of RRM (2 MUL or 1 MUL) and purification using BigDye((r))
      XTerminator(TM) (Applied Biosystems) instead of columns showed no loss of
      sequence length and increased the quality and the sensitivity of testing,
      allowing HVI and HVII typing from mitochondrial genome equivalent to 125 fg of
      nuclear DNA, or 100 pg of HVI/HVII amplicons. Using this methodology, testing can
      be completed in 1 day, and the cost of testing is reduced.

PMID- 24666099
TI  - Influences of multiple tooth-loss on signal travel in the insular cortex of rats.
AB  - The insular cortex (IC) processes various kinds of sensory and emotional
      information. Multiple tooth-loss induces impairment of oral sensory and motor
      functions, which might result in the up- or down-regulation of signal processing
      in the IC. In the present study, we investigated how multiple tooth-loss affects
      neural activities in the IC. Slices of the IC were prepared from control
      (untreated) rats and rats raised following the loss of their upper molar teeth,
      and optical recordings with voltage-sensitive dye were made. Electrical
      stimulation was delivered to the agranular IC (AIC). The velocity of optical
      signal from the AIC to the granular IC (GIC) decreased in multiple tooth-loss
      rats compared with control rats. Field potentials from the GIC were recorded.
      Onset times of evoked response at the GIC recorded from multiple tooth-loss rats
      were prolonged compared with those recorded from control rats, suggesting that
      signal velocity in multiple tooth-loss rats had decreased. A reduced signal
      velocity was accompanied by neuronal loss in the GIC, which was confirmed by
      counting the cell numbers on Nissl-stained sections. Thus, multiple tooth-loss
      may have influences on the GIC where signal processing speed decreases.

PMID- 24666100
TI  - Interconversion of eta3-H2SiRR' sigma-complexes and 16-electron silylene
      complexes via reversible H-H or C-H elimination.
AB  - Solid samples of eta(3)-silane complexes [PhBP(Ph)3]RuH(eta(3)-H2SiRR') (R,R' =
      Et2, 1a; PhMe, 1b; Ph2, 1c, MeMes, 1d) decompose when exposed to dynamic vacuum.
      Gas-phase H2/D2 exchange between isolated, solid samples of 1c-d3 and 1c indicate
      that a reversible elimination of H2 is the first step in the irreversible
      decomposition. An efficient solution-phase trap for hydrogen, the 16-electron
      ruthenium benzyl complex [PhBP(Ph)3]Ru[eta(3)-CH2(3,5-Me2C6H3)] (3) reacts
      quantitatively with H2 in benzene via elimination of mesitylene to form the
      eta(5)-cyclohexadienyl complex [PhBP(Ph)3]Ru(eta(5)-C6H7) (4). This H2 trapping
      reaction was utilized to drive forward and quantify the elimination of H2 from
      1b,d in solution, which resulted in the decomposition of 1b,d to form 4 and
      several organosilicon products that could not be identified. Reaction of
      {[PhBP(Ph)3]Ru(MU-Cl)}2 (2) with (THF)2Li(SiHMes2) forms a new eta(3)-H2Si
      species [PhBP(Ph)3]Ru[CH2(2-(eta(3)-H2SiMes)-3,5-Me2C6H2)] (5) which reacts with
      H2 to form the eta(3)-H2SiMes2 complex [PhBP(Ph)3]RuH(eta(3)-H2SiMes2) (1e).
      Complex 1e was identified by NMR spectroscopy prior to its decomposition by
      elimination of Mes2SiH2 to form 4. DFT calculations indicate that an isomer of 5,
      the 16-electron silylene complex [PhBP(Ph)3]Ru(MU-H)(?SiMes2), is only 2 kcal/mol
      higher in energy than 5. Treatment of 5 with XylNC (Xyl = 2,6-dimethylphenyl)
      resulted in trapping of [PhBP(Ph)3]Ru(MU-H)(?SiMes2) to form the 18-electron
      silylene complex [PhBP(Ph)3]Ru(CNXyl)(MU-H)(?SiMes2) (6). A closely related
      germylene complex [PhBP(Ph)3]Ru[CN(2,6-diphenyl-4-MeC6H2)](H)(?GeH(t)Bu) (8) was
      prepared from reaction of (t)BuGeH3 with the benzyl complex [PhBP(Ph)3]Ru[CN(2,6
      diphenyl-4-MeC6H2)][eta(1)-CH2(3,5-Me2C6H3)] (7). Single crystal XRD analysis
      indicated that unlike for 6, the hydride ligand in 8 is a terminal hydride that
      does not engage in 3c-2e Ru-H -> Ge bonding. Complex 1b is an effective
      precatalyst for the catalytic Ge-H dehydrocoupling of (t)BuGeH3 to form
      ((t)BuGeH2)2 (85% yield) and H2. 

PMID- 24666101
TI  - Kinetochore composition and its function: lessons from yeasts.
AB  - Proper chromosome segregation during cell division is essential for
      proliferation, and this is facilitated by kinetochores, large protein complexes
      assembled on the centromeric region of the chromosomes. Although the sequences of
      centromeric DNA differ totally among organisms, many components of the
      kinetochores assembled on centromeres are very well conserved among eukaryotes.
      To define the identity of centromeres, centromere protein A (CENP-A), which is
      homologous to canonical histone H3, acts as a landmark for kinetochore assembly.
      Kinetochores mediate spindle-microtubule attachment and control the movement of
      chromosomes during mitosis and meiosis. To conduct faithful chromosome
      segregation, kinetochore assembly and microtubule attachment are elaborately
      regulated. Here we review the current understanding of the composition, assembly,
      functions and regulation of kinetochores revealed mainly through studies on
      fission and budding yeasts. Moreover, because recent cumulative evidence suggests
      the importance of the regulation of the orientation of kinetochore-microtubule
      attachment, which differs distinctly between mitosis and meiosis, we focus
      especially on the molecular mechanisms underlying this regulation.

PMID- 24666102
TI  - Tumour characteristics and surgical treatment of renal cell carcinoma in Sweden
      2005-2010: a population-based study from the national Swedish kidney cancer
      register.
AB  - OBJECTIVE: Tumour characteristics, preoperative work-up and surgical treatment in
      patients diagnosed with renal cell carcinoma (RCC) between 2005 and 2010, and
      changes over time were studied in a national population-based cohort. MATERIAL
      AND METHODS: The National Swedish Kidney Cancer Register (NSKCR) contains
      information on histopathology, Fuhrman grade and clinical stage at presentation,
      and on the preoperative work-up and surgical treatment of patients with RCC.
      Between 2005 and 2010, 5553 RCC patients were registered in the NSKCR, 99% of
      those registered in the National Cancer Registry. RESULTS: During the study
      period the mean tumour size decreased from 70 to 64 mm (p = 0.024) and the
      frequency of metastatic RCC decreased from 22% to 15% (p < 0.001). The use of
      preoperative chest computed tomography increased from 59% to 84%. In total, 4229
      (76%) patients were treated with curative intent, 3453 (82%) underwent radical
      nephrectomy, 606 (14%) partial nephrectomy (PN) and 170 (4%) cryotherapy or
      radiofrequency ablation. In tumours up to 4 cm, PN was performed in 33% of the
      surgically treated patients. PN irrespective of size increased from 8% to 20% and
      laparoscopic nephrectomy increased from 6% to 17% during the period. In patients
      with metastatic RCC, 55% underwent cytoreductive nephrectomy. CONCLUSIONS: The
      NSKCR explores population-based data on the clinical handling of patients with
      RCC. This study, between 2005 and 2010, shows significant decrease in tumour size
      and metastatic RCC at presentation, a more complete preoperative work-up, and
      significantly increased use of PN and laparoscopic nephrectomy in Sweden.

PMID- 24666103
TI  - Practice patterns for the surgical treatment of T1 renal cell carcinoma: a
      nationwide population-based register study.
AB  - OBJECTIVE: Treatment of renal cell carcinoma (RCC) with radical nephrectomy (RN)
      induces chronic kidney disease more frequently compared with nephron-sparing
      surgery (NSS), which may have an impact on overall survival. Thus, NSS is
      recommended for RCCs up to 7 cm (T1). The aim of this study was to determine the
      extent to which these recommendations are implemented in clinical practice.
      MATERIAL AND METHODS: Data were extracted from the Swedish National Kidney Cancer
      Register, a population-based register covering 98% of all RCCs in Sweden. In
      total, 3158 patients (1892 men, 1266 women) were primarily diagnosed with cT1N0M0
      and treated surgically during 2005-2011. The administered treatments were
      evaluated between different hospitals as well as between the 21 independent
      healthcare counties. RESULTS: In all, 742 patients were treated with NSS, 2339
      with RN and 77 with minimally invasive ablative treatments. For cT1a RCC,
      patients treated with NSS increased from 22% in 2005 to 53% in 2011, and for cT1b
      from 2% to 10%. Nephron-sparing treatments for cT1a RCC were performed in 62% in
      university hospitals, 34% in intermediate- and 11% in low-volume hospitals. There
      was significant (p < 0.001) variation (31-67%) between the university hospitals
      and also for patient care in the 21 different counties (16-78%). There was an
      increased relative survival after NSS for T1a patients compared with RN. The
      register design by itself indicates limitations using data gathered from all
      Swedish hospitals. CONCLUSIONS: NSS was underutilized in many hospitals and a
      patient's chance of being offered NSS varied according to their place of
      residence. Patients with cT1a RCC treated with NSS had a significantly better
      relative survival than those treated with RN.

PMID- 24666104
TI  - A review of real-world data on the effects of aripiprazole on weight and
      metabolic outcomes in adults.
AB  - BACKGROUND: Metabolic abnormalities observed with atypical antipsychotic
      treatment may be specific to each antipsychotic medication. The association
      between atypical antipsychotics and risk factors for cardiovascular disease
      prompted the American Diabetes Association (ADA) and the American Psychiatric
      Association (APA) to issue a consensus statement that categorized aripiprazole
      and ziprasidone as atypical antipsychotics with a lower likelihood of metabolic
      abnormalities. OBJECTIVE: The aim of the current systematic review was to
      evaluate real-world studies (i.e. observational/naturalistic and open-label
      studies) assessing the risk for weight gain, dyslipidemia, glucose abnormalities,
      and diabetes mellitus in adult patients receiving treatment with atypical
      antipsychotics, with a specific focus on aripiprazole. METHODS: A systematic
      PubMed search for articles published between 1 January 2000 and 4 October 2011
      was performed using the following search terms in the title and abstract:
      aripiprazole, atypical, glucose, insulin, cholesterol, triglycerides, diabetes,
      hemoglobin A1c, weight, body mass index, and hyperlipidemia. RESULTS: Twenty-two
      peer-reviewed articles were found that assessed the metabolic effects associated
      with aripiprazole treatment, including studies from small observational trials to
      large databases (n = 15 to n > 1,700,000). Thirteen articles reported
      observational or naturalistic studies, and nine were open-label trials evaluating
      weight gain, dyslipidemia, glucose abnormalities, and the risk of developing
      diabetes in adult patients receiving treatment with aripiprazole. Compared with
      other atypical antipsychotics, aripiprazole was either less likely to have an
      impact or had a comparable impact on weight gain and dyslipidemia; the degree of
      effect appeared to be dependent on study design. In addition, there was less risk
      of diabetes mellitus with aripiprazole compared with most other atypical
      antipsychotic agents. CONCLUSIONS: Consistent with data from randomized
      controlled studies, the current review of observational/naturalistic and open
      label studies suggests aripiprazole may be associated with a lower risk than
      other commonly used atypical antipsychotics for metabolic adverse events in
      adults, consistent with the ADA/APA consensus statement.

PMID- 24666106
TI  - MK-5172 : a second-generation protease inhibitor for the treatment of hepatitis C
      virus infection.
AB  - INTRODUCTION: Approximately 170 million people worldwide are chronic carriers of
      the hepatitis C virus (HCV). Twenty-five percent of them develop liver cirrhosis
      and hepatocellular carcinoma during their life. Successful antiviral treatment
      dramatically reduces the risk of disease progression. HCV infection is treated
      with pegylated interferon and ribavirin; the addition of a protease inhibitor
      (boceprevir or telaprevir) can also be considered for patients with genotype 1.
      AREAS COVERED: This review summarizes the data about the pharmacokinetics,
      pharmacodynamics, efficacy and safety of MK-5172 , a second-generation inhibitor
      of HCV NS3/4A protease. EXPERT OPINION: The pharmacokinetic profile allows for
      once-a-day administration. Combined with pegylated interferon and ribavirin, MK
      5172 results in a high rate of HCV eradication (in about 90% of cases) and a
      better outcome than boceprevir-based triple therapy. Also in interferon-free
      combinations, MK-5172-associated eradication rates are very high (89 - 100%). MK
      5172 has a higher barrier to resistance than first-generation protease inhibitors
      and is active against most variants associated with resistance to first
      generation protease inhibitors. Tolerability and safety profile are good.
      Although data are limited, MK-5172 appears to overcome most of the drawbacks of
      the first-generation protease inhibitors and is thus a very promising agent to be
      used in combination with other antivirals to eradicate HCV infection.

PMID- 24666107
TI  - Effects and mechanisms of ginseng and ginsenosides on cognition.
AB  - Reviewed here is the existing evidence for the effects of ginseng extracts and
      isolated ginsenosides relevant to cognition in humans. Clinical studies in
      healthy volunteers and in patients with neurological disease or deficit, evidence
      from preclinical models of cognition, and pharmacokinetic data are considered.
      Conditions under which disease modification may indirectly benefit cognition but
      may not translate to cognitive benefits in healthy subjects are discussed. The
      number of chronic studies of ginseng effects in healthy individuals is limited,
      and the results from acute studies are inconsistent, making overall assessment of
      ginseng's efficacy as a cognitive enhancer premature. However, mechanistic
      results are encouraging; in particular, the ginsenosides Rg3 , Rh1 , Rh2 , Rb1 ,
      Rd, Rg2 , and Rb3 , along with the aglycones protopanaxadiol and
      protopanaxatriol, warrant further attention. Compound K has a promising
      pharmacokinetic profile and can affect neurotransmission and neuroprotection.
      Properly conducted trials using standardized tests in healthy individuals
      reflecting the target population for ginseng supplementation are required to
      address inconsistencies in results from acute studies. The evidence summarized
      here suggests ginseng has potential, but unproven, benefits on cognition. 

PMID- 24666109
TI  - Acute effects of normobaric hypoxia on hand-temperature responses during and
      after local cold stress.
AB  - The purpose was to investigate acute effects of normobaric hypoxia on hand
      temperature responses during and after a cold-water hand immersion test. Fifteen
      males performed two right-hand immersion tests in 8 degrees C water, during which
      they were inspiring either room air (Fio2: 0.21; AIR), or a hypoxic gas mixture
      (Fio2: 0.14; HYPO). The tests were conducted in a counterbalanced order and
      separated by a 1-hour interval. Throughout the 30-min cold-water immersion (CWI)
      and the 15-min spontaneous rewarming (RW) phases, finger-skin temperatures were
      measured continuously with thermocouple probes; infrared thermography was also
      employed during the RW phase to map all segments of the hand. During the CWI
      phase, the average skin temperature (Tavg) of the fingers did not differ between
      the conditions (AIR: 10.2 +/- 0.5 degrees C, HYPO: 10.0 +/- 0.5 degrees C; p =
      0.67). However, Tavg was lower in the HYPO than the AIR RW phase (AIR: 24.5 +/-
      3.4 degrees C; HYPO: 22.0 +/- 3.8 degrees C; p = 0.002); a response that was
      alike in all regions of the immersed hand. Accordingly, present findings suggest
      that acute exposure to normobaric hypoxia does not aggravate the cold-induced
      drop in hand temperature of normothermic males. Still, hypoxia markedly impairs
      the rewarming responses of the hand.

PMID- 24666110
TI  - Beneficial effects of melatonin on in vitro bovine embryonic development are
      mediated by melatonin receptor 1.
AB  - In the current study, a fundamental question, that is, the mechanisms related to
      the beneficial effects of melatonin on mammalian embryonic development, was
      addressed. To examine the potential beneficial effects of melatonin on bovine
      embryonic development, different concentrations of melatonin (10(-11), 10(-9),
      10(-7), 10(-5), 10(-3) M) were incubated with fertilized embryos. Melatonin in
      the range of 10(-11) to 10(-5) M significantly promoted embryonic development
      both in early culture medium (CR1aa +3 mg/mL BSA) and in later culture medium
      (CR1aa + 6%FBS). The most effective concentrations applied in the current studies
      were 10(-9) and 10(-7) M. Using quantitative real-time PCR with
      immunofluorescence and Western blot assays, the expression of melatonin receptor
      MT1 and MT2 genes was identified in bovine embryos. Further studies indicate that
      the beneficial effects of melatonin on bovine embryo development were mediated by
      the MT1 receptor. This is based on the facts that luzindole, a nonselective MT1
      and MT2 antagonist, blocked the effect on melatonin-induced embryo development,
      while 4-P-PDOT, a selective MT2 antagonist, had little effect. Mechanistic
      explorations uncovered that melatonin application during bovine embryonic
      development significantly up-regulated the expression of antioxidative (Gpx4,
      SOD1, bcl-2) and developmentally important genes (SLC2A1, DNMT1A, and DSC2) while
      down-regulating expression of pro-apoptotic genes (P53, BAX, and Caspase-3). The
      results obtained from the current studies provide new information regarding the
      mechanisms by which melatonin promotes bovine embryonic development under both in
      vitro and in vivo conditions.

PMID- 24666108
TI  - Lessons from helminth infections: ES-62 highlights new interventional approaches
      in rheumatoid arthritis.
AB  - Parasitic worms are able to survive in their mammalian host for many years due to
      their ability to manipulate the immune response by secreting immunomodulatory
      products. It is increasingly clear that, reflecting the anti-inflammatory actions
      of such worm-derived immunomodulators, there is an inverse correlation between
      helminth infection and autoimmune diseases in the developing world. As the
      decrease in helminth infections due to increased sanitation has correlated with
      an alarming increase in prevalence of such disorders in industrialized countries,
      this 'hygiene hypothesis' has led to the proposal that worms and their secreted
      products offer a novel platform for the development of safe and effective
      strategies for the treatment of autoimmune disorders. In this study we review the
      anti-inflammatory effects of one such immunomodulator, ES-62 on innate and
      adaptive immune responses and the mechanisms it exploits to afford protection in
      the murine collagen-induced arthritis (CIA) model of rheumatoid arthritis (RA).
      As its core mechanism involves targeting of interleukin (IL)-17 responses, which
      despite being pathogenic in RA are important for combating infection, we discuss
      how its selective targeting of IL-17 production by T helper type 17 (Th17) and
      gammadelta T cells, while leaving that of CD49b(+) natural killer (NK and NK T)
      cells intact, reflects the ability of helminths to modulate the immune system
      without immunocompromising the host. Exploiting helminth immunomodulatory
      mechanisms therefore offers the potential for safer therapies than current
      biologicals, such as 'IL-17 blockers', that are not able to discriminate sources
      of IL-17 and hence present adverse effects that limit their therapeutic
      potential. 

PMID- 24666111
TI  - Can we predict recovery from severe acute kidney injury with biomarkers?

PMID- 24666112
TI  - Evaluation of HLA-DRB1 imputation using a Finnish dataset.
AB  - Owing to the vast amount of alleles, high-resolution human leukocyte antigen
      (HLA) typing is expensive and time-consuming. Scientists have attempted to
      develop computational approaches to define HLA alleles with high confidence. We
      tested the reliability of HLA*IMP and SNP2HLA for imputing HLA-DRB1 alleles in a
      Finnish material (n=161). The per-individual success rates varied between 16.68%
      and 25.4% using both softwares. One of the most prominent example was HLA
      DRB1*01:01 allele showing approximately a 30% success rate while being the most
      common wrongly imputed allele. In Finland, isolation and migration history have
      shaped the gene pool narrower showing HLA haplotype frequencies typical to the
      Finnish population when compared to Europeans. The imputation success for HLA
      DRB1 alleles was very low pointing to the importance of population-specific
      reference material.

PMID- 24666113
TI  - Hypertonic saline for cystic fibrosis: worth its salt?
AB  - Airway dehydration in cystic fibrosis (CF) leads to chronic inflammation, ongoing
      infection and progressive lung disease. Restoration of airway hydration by
      inhalation of an osmotic agent (hypertonic saline) has been shown to be safe,
      effective and well-tolerated in adults with CF. Although the safety of hypertonic
      saline in infants and young children with CF has also been established, recent
      studies have reported inconclusive evidence about its efficacy. In this
      editorial, we discuss the evidence behind hypertonic saline use for adults,
      children and infants with CF.

PMID- 24666114
TI  - Headache care in China.
AB  - Headache disorders are problematic worldwide. China is no different. A population
      based door-to-door survey revealed that the 1-year prevalence of primary headache
      disorders in China was 23.8%, constituting a major societal burden. Many headache
      centers and clinics have been established in China, and headache disorders (and
      associated stress) are receiving an increased level of expert attention. This
      review summarizes the outcomes of the epidemiological survey and the progress of
      clinical and basic research in China, describes the present situation in terms of
      headache diagnosis and treatment, and discusses the future of headache care in
      China. 

PMID- 24666115
TI  - Well-defined hydrophilic molecularly imprinted polymer microspheres for efficient
      molecular recognition in real biological samples by facile RAFT coupling
      chemistry.
AB  - A facile and highly efficient new approach (namely RAFT coupling chemistry) to
      obtain well-defined hydrophilic molecularly imprinted polymer (MIP) microspheres
      with excellent specific recognition ability toward small organic analytes in the
      real, undiluted biological samples is described. It involves the first synthesis
      of "living" MIP microspheres with surface-bound vinyl and dithioester groups via
      RAFT precipitation polymerization (RAFTPP) and their subsequent grafting of
      hydrophilic polymer brushes by the simple coupling reaction of hydrophilic macro
      RAFT agents (i.e., hydrophilic polymers with a dithioester end group) with vinyl
      groups on the "living" MIP particles in the presence of a free radical initiator.
      The successful grafting of hydrophilic polymer brushes onto the obtained MIP
      particles was confirmed by SEM, FT-IR, static contact angle and water dispersion
      studies, elemental analyses, and template binding experiments. Well-defined MIP
      particles with densely grafted hydrophilic polymer brushes (~1.8 chains/nm(2)) of
      desired chemical structures and molecular weights were readily obtained, which
      showed significantly improved surface hydrophilicity and could thus function
      properly in real biological media. The origin of the high grafting densities of
      the polymer brushes was clarified and the general applicability of the strategy
      was demonstrated. In particular, the well-defined characteristics of the
      resulting hydrophilic MIP particles allowed the first systematic study on the
      effects of various structural parameters of the grafted hydrophilic polymer
      brushes on their water-compatibility, which is of great importance for rationally
      designing more advanced real biological sample-compatible MIPs. 

PMID- 24666116
TI  - Local and collective reaction coordinates in the transport of the aqueous
      hydroxide ion.
AB  - We investigate local and collective reaction coordinates for the structural
      diffusion of the hydroxide ion in dilute aqueous NaOH solution using a multistate
      empirical valence bond (MS-EVB) simulation. We characterize a 15 fs time scale
      associated with shifting of the equally shared proton within a Zundel-like H3O2(
      ) ion to form a water molecule, a 550 fs relaxation from this transition state
      largely guided by electrostatic fluctuations of the surrounding environment, and
      a 9.6 ps time scale that corresponds to the solvation of the water molecule
      formed by the proton transfer event. When individual proton transfer events are
      examined, we are unable to identify a unique transition state solely on the basis
      of a decrease in the hydroxide ion's coordination number. Instead, we find that
      the collective electric field along the proton transfer direction is better
      suited to describe the creation and relaxation of Zundel-like transition states
      that allow structural diffusion of the hydroxide ion. 

PMID- 24666117
TI  - The use of an alternate light source for detecting bones underwater.
AB  - When searching underwater crime scenes or disaster scenes for fragmentary human
      remains, it may be advantageous for forensic divers to be able to detect the
      presence of bones and teeth among other marine materials (such as shells and
      rocks). In terrestrial environments, this can typically be accomplished by visual
      and instrumental methods, but underwater conditions make it difficult to employ
      detection and sorting techniques in these environments. This study investigates
      fluorescence of bones and teeth and other marine materials using a submersible
      alternate light source (ALS) and concludes that an ALS can be a useful tool for
      detecting bones and teeth in underwater searches as well in terrestrial searches
      and laboratory environments. The results could impact the methods and equipment
      used by forensic divers and forensic anthropologists when searching for skeletal
      remains, potentially increasing the quantity and efficiency of forensic evidence
      recovered. 

PMID- 24666119
TI  - Biotechnological production and applications of Cordyceps militaris, a valued
      traditional Chinese medicine.
AB  - Cordyceps militaris is a potential harborer of biometabolites for herbal drugs.
      For a long time, C. militaris has gained considerable significance in several
      clinical and biotechnological applications. Much knowledge has been gathered with
      regard to the C. militaris's importance in the genetic resources, nutritional and
      environmental requirements, mating behavior and biochemical pharmacological
      properties. The complete genome of C. militaris has recently been sequenced. This
      fungus has been the subject of many reviews, but few have focused on its
      biotechnological production of bioactive constituents. This mini-review focuses
      on the recent advances in the biotechnological production of bioactive
      compositions of C. militaris and the latest advances on novel applications from
      this laboratory and many others. 

PMID- 24666118
TI  - Engineering Saccharomyces cerevisiae for direct conversion of raw, uncooked or
      granular starch to ethanol.
AB  - The production of raw starch-degrading amylases by recombinant Saccharomyces
      cerevisiae provides opportunities for the direct hydrolysis and fermentation of
      raw starch to ethanol without cooking or exogenous enzyme addition. Such a
      consolidated bioprocess (CBP) for raw starch fermentation will substantially
      reduce costs associated with energy usage and commercial granular starch
      hydrolyzing (GSH) enzymes. The core purpose of this review is to provide
      comprehensive insight into the physiological impact of recombinant amylase
      production on the ethanol-producing yeast. Key production parameters, based on
      outcomes from modifications to the yeast genome and levels of amylase production,
      were compared to key benchmark data. In turn, these outcomes are of significance
      from a process point of view to highlight shortcomings in the current state of
      the art of raw starch fermentation yeast compared to a set of industrial
      standards. Therefore, this study provides an integrated critical assessment of
      physiology, genetics and process aspects of recombinant raw starch fermenting
      yeast in relation to presently used technology. Various approaches to strain
      development were compared on a common basis of quantitative performance measures,
      including the extent of hydrolysis, fermentation-hydrolysis yield and
      productivity. Key findings showed that levels of alpha-amylase required for raw
      starch hydrolysis far exceeded enzyme levels for soluble starch hydrolysis,
      pointing to a pre-requisite for excess alpha-amylase compared to glucoamylase for
      efficient raw starch hydrolysis. However, the physiological limitations of
      amylase production by yeast, requiring high biomass concentrations and long
      cultivation periods for sufficient enzyme accumulation under anaerobic
      conditions, remained a substantial challenge. Accordingly, the fermentation
      performance of the recombinant S. cerevisiae strains reviewed in this study could
      not match the performance of conventional starch fermentation processes, based
      either on starch cooking and/or exogenous amylase enzyme addition. As an
      alternative strategy, the addition of exogenous GSH enzymes during early stages
      of raw starch fermentation may prove to be a viable approach for industrial
      application of recombinant S. cerevisiae, with the process still benefitting from
      amylase production by CBP yeast during later stages of cultivation. 

PMID- 24666120
TI  - Steatocystoma multiplex associated with bilateral preauricular sinuses.
AB  - Steatocystoma multiplex is characterized by the development of numerous
      steatocystomas. The condition has occasionally been related to congenital
      bilateral preauricular sinuses. Herein, we present the third case of such an
      association, a 34-year-old male who was born with bilateral preauricular sinuses
      that were surgically repaired. When he was 14 years old, he presented with
      multiple steatocystomas on his forehead and temples, one of which was biopsied.
      There was no family history of the condition. 

PMID- 24666121
TI  - Mesoporous silica nanoparticles/hydroxyapatite composite coated implants to
      locally inhibit osteoclastic activity.
AB  - In an attempt to improve implant-bone integration and accelerate bone fracture
      healing from resisting osteoclastic resorption point of view, we have employed a
      novel procedure to develop a mesoporous silica nanoparticles/hydroxyapatite
      (MSNs/HA) composite coating onto stainless Kirschner wire substrate.
      Characterizations of the surface microstructures indicated enlarged specific
      surface area compared to HA-coated wires as control, thus the MSNs/HA composite
      coated implants are endowed with abilities to locally deliver biomedical
      substances and enhance fracture healing. Herein, zoledronic acid (ZOL) as a model
      drug, different doses of which were immobilized in the mesoporous coating toward
      decreasing osteoclastic resorption activity. The loading capacities of ZOL
      increased almost eight-folds to that of pure HA coating, and the introduction of
      MSNs obviously retarded ZOL release to achieve a more sustained release profile.
      After certain periods of osteoclast like cells co-culturing with ZOL contained
      wires, tartrat-resistant acid phosphatases (TRAP) staining of polynucleated cells
      and a pit formation assay were performed to investigate the ZOL dose-dependent
      anti-resorption activity. The promoted local effect on osteoclasts will be of
      clinical benefit to support implant integration and bone repair. 

PMID- 24666123
TI  - The impact of childhood experience on amygdala response to perceptually familiar
      black and white faces.
AB  - Given the well-documented involvement of the amygdala in race perception, the
      current study aimed to investigate how interracial contact during childhood
      shapes amygdala response to racial outgroup members in adulthood. Of particular
      interest was the impact of childhood experience on amygdala response to familiar,
      compared with novel, Black faces. Controlling for a number of well-established
      individual difference measures related to interracial attitudes, the results
      reveal that perceivers with greater childhood exposure to racial outgroup members
      display greater relative reduction in amygdala response to familiar Black faces.
      The implications of such findings are discussed in the context of previous
      investigations into the neural substrates of race perception and in consideration
      of potential mechanisms by which childhood experience may shape race perception. 

PMID- 24666122
TI  - Medical ethical standards in dermatology: an analytical study of knowledge,
      attitudes and practices.
AB  - BACKGROUND: Dermatology practice has not been ethically justified at all times.
      OBJECTIVE: The objective of the study was to find out dermatologists' knowledge
      about medical ethics, their attitudes towards regulatory measures and their
      practices, and to study the different factors influencing the knowledge, the
      attitude and the practices of dermatologists. METHODS: This is a cross-sectional
      comparative study conducted among 214 dermatologists, from five Academic
      Universities and from participants in two conferences. A 54 items structured
      anonymous questionnaire was designed to describe the demographical
      characteristics of the study group as well as their knowledge, attitude and
      practices regarding the medical ethics standards in clinical and research
      settings. Five scoring indices were estimated regarding knowledge, attitude and
      practice. Inferential statistics were used to test differences between groups as
      indicated. The Student's t-test and analysis of variance were carried out for
      quantitative variables. The chi-squared test was conducted for qualitative
      variables. The results were considered statistically significant at a P > 0.05.
      RESULTS: Analysis of the possible factors having impact on the overall scores
      revealed that the highest knowledge scores were among dermatologists who practice
      in an academic setting plus an additional place; however, this difference was
      statistically non-significant (P = 0.060). Female dermatologists showed a higher
      attitude score compared to males (P = 0.028). The highest significant attitude
      score (P = 0.019) regarding clinical practice was recorded among those practicing
      cosmetic dermatology. The different studied groups of dermatologists revealed a
      significant impact on the attitude score (P = 0.049), and the evidence-practice
      score (P < 0.001). CONCLUSION: Ethical practices will improve the quality and
      integrity of dermatology research.

PMID- 24666124
TI  - Persistent hemispheric differences in the perceptual selection of spatial
      frequencies.
AB  - Previous research has shown that the right hemisphere processes low spatial
      frequencies more efficiently than the left hemisphere, which preferentially
      processes high spatial frequencies. These studies have typically measured RTs to
      single, briefly flashed gratings and/or have directed observers to attend to a
      particular spatial frequency immediately before making a judgment about a
      subsequently presented stimulus. Thus, it is unclear whether the hemispheres
      differ in perceptual selection from multiple spatial frequencies that are
      simultaneously present in the environment, without bias from selective attention.
      Moreover, the time course of hemispheric asymmetry in spatial frequency
      processing is unknown. We addressed both of these questions with binocular
      rivalry, a measure of perceptual selection from competing alternatives over time.
      Participants viewed a pair of rivalrous orthogonal gratings with different
      spatial frequencies, presented either to the left or right of central fixation,
      and continuously reported which grating they perceived. At the beginning of a
      trial, the low spatial frequency grating was perceptually selected more often
      when presented in the left hemifield (right hemisphere) than in the right
      hemifield (left hemisphere), whereas the high spatial frequency grating showed
      the opposite pattern of results. This hemispheric asymmetry in perceptual
      selection persisted for the entire 30-sec stimulus presentation, continuing long
      after stimulus onset. These results indicate stable differences in the resolution
      of ambiguity across spatial locations and demonstrate the importance of
      considering sustained differences in perceptual selection across space when
      characterizing conscious representations of complex scenes. 

PMID- 24666125
TI  - Visual memory in unilateral spatial neglect: immediate recall versus delayed
      recognition.
AB  - Patients with unilateral spatial neglect (USN) often show impaired performance in
      spatial working memory tasks, apart from the difficulty retrieving "left-sided"
      spatial data from long-term memory, shown in the "piazza effect" by Bisiach and
      colleagues. This study's aim was to compare the effect of the spatial position of
      a visual object on immediate and delayed memory performance in USN patients.
      Specifically, immediate verbal recall performance, tested using a simultaneous
      presentation of four visual objects in four quadrants, was compared with memory
      in a later-provided recognition task, in which objects were individually shown at
      the screen center. Unlike healthy controls, USN patients showed a left-side
      disadvantage and a vertical bias in the immediate free recall task (69% vs. 42%
      recall for right- and left-sided objects, respectively). In the recognition task,
      the patients correctly recognized half of "old" items, and their correct
      rejection rate was 95.5%. Importantly, when the analysis focused on previously
      recalled items (in the immediate task), no statistically significant difference
      was found in the delayed recognition of objects according to their original
      quadrant of presentation. Furthermore, USN patients were able to recollect the
      correct original location of the recognized objects in 60% of the cases, well
      beyond chance level. This suggests that the memory trace formed in these cases
      was not only semantic but also contained a visuospatial tag. Finally, successful
      recognition of objects missed in recall trials points to formation of memory
      traces for neglected contralesional objects, which may become accessible to
      retrieval processes in explicit memory. 

PMID- 24666126
TI  - Mapping the semantic structure of cognitive neuroscience.
AB  - Cognitive neuroscience, as a discipline, links the biological systems studied by
      neuroscience to the processing constructs studied by psychology. By mapping these
      relations throughout the literature of cognitive neuroscience, we visualize the
      semantic structure of the discipline and point to directions for future research
      that will advance its integrative goal. For this purpose, network text analyses
      were applied to an exhaustive corpus of abstracts collected from five major
      journals over a 30-month period, including every study that used fMRI to
      investigate psychological processes. From this, we generate network maps that
      illustrate the relationships among psychological and anatomical terms, along with
      centrality statistics that guide inferences about network structure. Three terms-
      prefrontal cortex, amygdala, and anterior cingulate cortex--dominate the network
      structure with their high frequency in the literature and the density of their
      connections with other neuroanatomical terms. From network statistics, we
      identify terms that are understudied compared with their importance in the
      network (e.g., insula and thalamus), are underspecified in the language of the
      discipline (e.g., terms associated with executive function), or are imperfectly
      integrated with other concepts (e.g., subdisciplines like decision neuroscience
      that are disconnected from the main network). Taking these results as the basis
      for prescriptive recommendations, we conclude that semantic analyses provide
      useful guidance for cognitive neuroscience as a discipline, both by illustrating
      systematic biases in the conduct and presentation of research and by identifying
      directions that may be most productive for future research.

PMID- 24666127
TI  - Idiosyncratic grammars: syntactic processing in second language comprehension
      uses subjective feature representations.
AB  - Learning the syntax of a second language (L2) often represents a big challenge to
      L2 learners. Previous research on syntactic processing in L2 has mainly focused
      on how L2 speakers respond to "objective" syntactic violations, that is, phrases
      that are incorrect by native standards. In this study, we investigate how L2
      learners, in particular those of less than near-native proficiency, process
      phrases that deviate from their own, "subjective," and often incorrect syntactic
      representations, that is, whether they use these subjective and idiosyncratic
      representations during sentence comprehension. We study this within the domain of
      grammatical gender in a population of German learners of Dutch, for which
      systematic errors of grammatical gender are well documented. These L2 learners as
      well as a control group of Dutch native speakers read Dutch sentences containing
      gender-marked determiner-noun phrases in which gender agreement was either
      (objectively) correct or incorrect. Furthermore, the noun targets were selected
      such that, in a high proportion of nouns, objective and subjective correctness
      would differ for German learners. The ERP results show a syntactic violation
      effect (P600) for objective gender agreement violations for native, but not for
      nonnative speakers. However, when the items were re-sorted for the L2 speakers
      according to subjective correctness (as assessed offline), the P600 effect
      emerged as well. Thus, rather than being insensitive to violations of gender
      agreement, L2 speakers are similarly sensitive as native speakers but base their
      sensitivity on their subjective-sometimes incorrect-representations.

PMID- 24666128
TI  - Disposed to distraction: genetic variation in the cholinergic system influences
      distractibility but not time-on-task effects.
AB  - Both the passage of time and external distraction make it difficult to keep
      attention on the task at hand. We tested the hypothesis that time-on-task and
      external distraction pose independent challenges to attention and that the
      brain's cholinergic system selectively modulates our ability to resist
      distraction. Participants with a polymorphism limiting cholinergic capacity
      (Ile89Val variant [rs1013940] of the choline transporter gene SLC5A7) and matched
      controls completed self-report measures of attention and a laboratory task that
      measured decrements in sustained attention with and without distraction. We found
      evidence that distraction and time-on-task effects are independent and that the
      cholinergic system is strongly linked to greater vulnerability to distraction.
      Ile89Val participants reported more distraction during everyday life than
      controls, and their task performance was more severely impacted by the presence
      of an ecologically valid video distractor (similar to a television playing in the
      background). These results are the first to demonstrate a specific impairment in
      cognitive control associated with the Ile89Val polymorphism and add to behavioral
      and cognitive neuroscience studies indicating the cholinergic system's critical
      role in overcoming distraction. 

PMID- 24666130
TI  - Moving mirrors: a high-density EEG study investigating the effect of camera
      movements on motor cortex activation during action observation.
AB  - Action execution-perception links (mirror mechanism) have been repeatedly
      suggested to play crucial roles in social cognition. Remarkably, the designs of
      most studies exploring this topic so far excluded even the simplest traces of
      social interaction, such as a movement of the observer toward another individual.
      This study introduces a new design by investigating the effects of camera
      movements, possibly simulating the observer's own approaching movement toward the
      scene. We conducted a combined high-density EEG and behavioral study
      investigating motor cortex activation during action observation measured by event
      related desynchronization and resynchronization (ERD/ERS) of the mu rhythm.
      Stimuli were videos showing a goal-related hand action filmed while using the
      camera in four different ways: filming from a fixed position, zooming in on the
      scene, approaching the scene by means of a dolly, and approaching the scene by
      means of a steadycam. Results demonstrated a consistently stronger ERD of the mu
      rhythm for videos that were filmed while approaching the scene with a steadycam.
      Furthermore, videos in which the zoom was applied reliably demonstrated a
      stronger rebound. A rating task showed that videos in which the camera approached
      the scene were felt as more involving and the steadycam was most able to produce
      a visual experience close to the one of a human approaching the scene. These
      results suggest that filming technique predicts time course specifics of ERD/ERS
      during action observation with only videos simulating the natural vision of a
      walking human observer eliciting a stronger ERD than videos filmed from a fixed
      position. This demonstrates the utility of ecologically designed studies for
      exploring social cognition. 

PMID- 24666129
TI  - Functional specialization within macaque dorsolateral prefrontal cortex for the
      maintenance of task rules and cognitive control.
AB  - The abilities of switching between and maintaining task rules are fundamental
      aspects of goal-oriented behavior. The PFC is thought to implement the cognitive
      processes underling such rule-based behavior, but the specific contributions of
      the several cytoarchitecturally distinct subfields of PFC remain poorly
      understood. Here, we used bilateral cryogenic deactivation to investigate the
      relative contributions of two regions of the dorsolateral PFC (dlPFC)--the
      inferior dlPFC (idlPFC) area, consisting of the cortex lining the caudal
      principal sulcus, and the dorsally adjacent superior dlPFC (sdlPFC)--to different
      aspects of rule-based behavior. Macaque monkeys performed two variants of a task
      that required them to alternate unpredictably between eye movements toward
      (prosaccade) or away from (antisaccade) a visual stimulus. In one version of the
      task, the current rule was overtly cued. In the second, the task rule was uncued,
      and successful performance required the animals to detect rule changes on the
      basis of reward outcome and subsequently maintain the current task rule within
      working memory. Deactivation of the idlPFC impaired the monkeys' ability to
      perform pro- and antisaccades in the uncued task only. In contrast, deactivation
      of the sdlPFC had no effect on performance in either task. Combined deactivation
      of idlPFC and sdlPFC impaired performance on antisaccade, but not prosaccade,
      trials in both task variants. These results suggest that the idlPFC is required
      for mnemonic processes involved in maintenance of task rules, whereas both idlPFC
      and sdlPFC together are necessary for the deployment of the cognitive control
      required to perform antisaccades. Together, these data support the concept of a
      functional specialization of subregions within the dlPFC for rule-guided
      behavior.

PMID- 24666131
TI  - Reach out and touch someone: anticipatory sensorimotor processes of active
      interpersonal touch.
AB  - Anticipating the sensorimotor consequences of an action for both self and other
      is fundamental for action coordination when individuals socially interact.
      Somatosensation constitutes an elementary component of social cognition and
      sensorimotor prediction, but its functions in active social behavior remain
      unclear. We hypothesized that the somatosensory system contributes to social
      haptic behavior as evidenced by specific anticipatory activation patterns when
      touching an animate target (human hand) compared with an inanimate target (fake
      hand). fMRI scanning was performed during a paradigm that allowed us to isolate
      the anticipatory representations of active interpersonal touch while controlling
      for nonsocial sensorimotor processes and possible confounds because of
      interpersonal relationships or socioemotional valence. Active interpersonal touch
      was studied both as skin-to-skin contact and as object-mediated touch. The
      results showed weaker deactivation in primary somatosensory cortex and medial pFC
      and stronger activation in cerebellum for the animate target, compared with the
      inanimate target, when intending to touch it with one's own hand. Differently, in
      anticipation of touching the human hand with an object, anterior inferior
      parietal lobule and lateral occipital-temporal cortex showed stronger activity.
      When actually touching a human hand with one's own hand, activation was stronger
      in medial pFC but weaker in primary somatosensory cortex. The findings provide
      new insight on the contribution of simulation and sensory prediction mechanisms
      to active social behavior. They also suggest that literally getting in touch with
      someone and touching someone by using an object might be approached by an agent
      as functionally distinct conditions. 

PMID- 24666132
TI  - Set-relevance determines the impact of distractors on episodic memory retrieval.
AB  - We investigated the interplay between stimulus-driven attention and memory
      retrieval with a novel interference paradigm that engaged both systems
      concurrently on each trial. Participants encoded a 45-min movie on Day 1 and, on
      Day 2, performed a temporal order judgment task during fMRI. Each retrieval trial
      comprised three images presented sequentially, and the task required participants
      to judge the temporal order of the first and the last images ("memory probes")
      while ignoring the second image, which was task irrelevant ("attention
      distractor"). We manipulated the content relatedness and the temporal proximity
      between the distractor and the memory probes, as well as the temporal distance
      between two probes. Behaviorally, short temporal distances between the probes led
      to reduced retrieval performance. Distractors that at encoding were temporally
      close to the first probe image reduced these costs, specifically when the
      distractor was content unrelated to the memory probes. The imaging results
      associated the distractor probe temporal proximity with activation of the right
      ventral attention network. By contrast, the precuneus was activated for high
      content relatedness between distractors and probes and in trials including a
      short distance between the two memory probes. The engagement of the right ventral
      attention network by specific types of distractors suggests a link between
      stimulus-driven attention control and episodic memory retrieval, whereas the
      activation pattern of the precuneus implicates this region in memory search
      within knowledge/content-based hierarchies. 

PMID- 24666133
TI  - Effects of search difficulty on the selection, maintenance, and learning of
      attentional templates.
AB  - Prominent theories of attention claim that visual search is guided through
      attentional templates stored in working memory. Recently, the contralateral delay
      activity (CDA), an electrophysiological index of working memory storage, has been
      found to rapidly decrease when participants repeatedly search for the same
      target, suggesting that, with learning, the template moves out of working memory.
      However, this has only been investigated with pop-out search for distinct
      targets, for which a strong attentional template may not be necessary. More
      effortful search tasks might rely more on an active attentional template in
      working memory, leading to a slower handoff to long-term memory and thus a slower
      decline of the CDA. Using ERPs, we compared the rate of learning of attentional
      templates in pop-out and effortful search tasks. In two experiments, the rate of
      decrease in the CDA was the same for both search tasks. Similar results were
      found for a second component indexing working memory effort, the late positive
      complex. However, the late positive complex was also sensitive to anticipated
      search difficulty, as was expressed in a greater amplitude before the harder
      search task. We conclude that the amount of working memory effort invested in
      maintaining an attentional template, but not the rate of learning, depends on
      search difficulty. 

PMID- 24666134
TI  - Response to androgen therapy in patients with dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and
      telomere biology disorder characterized by dysplastic nails, reticular skin
      pigmentation and oral leucoplakia. Androgens are a standard therapeutic option
      for bone marrow failure in those patients with DC who are unable to undergo
      haematopoietic stem cell transplantation, but there are no systematic data on its
      use in those patients. We evaluated haematological response and side effects of
      androgen therapy in 16 patients with DC in our observational cohort study.
      Untreated DC patients served as controls. Seventy percent of treated DC patients
      had a haematological response with red blood cell and/or platelet transfusion
      independence. The expected age-related decline in telomere length was noted in
      androgen-treated patients. All treated DC patients had at least one significant
      lipid abnormality. Additional treatment-related findings included a significant
      decrease in thyroid binding globulin, accelerated growth in pre-pubertal children
      and splenic peliosis in two patients. Liver enzymes were elevated in both
      androgen-treated and untreated patients, suggesting underlying liver involvement
      in DC. This study suggests that androgen therapy can be effectively used to treat
      bone marrow failure in DC, but that side effects need to be closely monitored.

PMID- 24666136
TI  - The ghost of fouling communities past: the effect of original community on
      subsequent recruitment.
AB  - Biofouling on ships has been linked to the spread of invasive species, which has
      been identified as one of the current primary threats to the environment.
      Previous research on antifouling coatings suggested that the quantity of fouling,
      as well as community composition, on biocidal coatings was modified by prior
      fouling settlement. The experiment reported in this paper was designed to
      determine how preconditioning affected the rate and composition of subsequent
      fouling on transplanted silicone coatings. A series of 10 * 20 cm panels coated
      with Intersleek 700 or DC3140 were placed at three locations in Florida (Ponce
      Inlet, Sebastian Inlet, and Port of Miami), which were characterized by distinct
      fouling communities. Panels were immersed for four months, cleaned, and
      reciprocally transplanted among the three sites. Fouling community composition
      and coverage were characterized at bimonthly intervals both before and after
      transplantation. The original fouling community affected the subsequent fouling
      composition and recolonization by tunicates, sea anemones, barnacles, sponges,
      hydroids, and arborescent bryozoans. The community-level effects were short-term,
      lasting 2-4 months, but specific responses lasted up to 14 months post
      transplant.

PMID- 24666135
TI  - Elevated rates of atypical handedness in paedophilia: theory and implications.
AB  - Multiple factors determine handedness including genetics, prenatal stress and
      post-natal environmental conditions. Atypical handedness, whether manifest as
      increased sinistrality or decreased strength of lateral preference, has been
      noted in a wide variety of populations with neuropathology. Those with atypical
      sexual preferences, specifically paedophilia, also manifest reduced rates of
      right-handedness. This paper uses the largest sample of phallometrically assessed
      men to date to establish the pattern of atypical handedness in paedophilia.
      Specifically, whereas prior research has largely characterized participants
      dichotomously as right-handed or non-right-handed and/or used self-report of
      writing hand, this paper expands upon such reports by using the Edinburgh
      Handedness Inventory's laterality quotient. Participants' handedness and
      phallometrically assessed sexual preference were analyzed both as continuous and
      categorical variables, and the responses of those scoring in the range of
      ambiguous-handedness were evaluated to ascertain whether they were ambiguously
      handed or more accurately described as mixed-handed. Results indicated those
      producing scores in the range of ambiguous-handedness demonstrated response
      patterns consistent with ambiguous-handedness, rather than mixed-handedness.
      Paedophiles demonstrated high rates of non-right-handedness primarily manifested
      as sinistrality, whereas those who had a sexual preference for pubescent children
      evidenced increased ambiguous-handedness. Results support a view of ambiguous
      handedness as less pathological than previously hypothesized, and of a
      neurodevelopmental origin of paraphilic sexual preferences. 

PMID- 24666137
TI  - Kinetics and thermodynamics of H-/H*/H+ transfer from a rhodium(III) hydride.
AB  - The thermodynamics and kinetics of all three cleavage modes for Rh-H, the
      transfer of H(-), H(+), or H*, have been studied for the Rh(III) hydride complex
      Cp*Rh(2-(2-pyridyl)phenyl)H (1a). The thermodynamic hydricity, DeltaG degrees H(
      ), for 1a has been measured (49.5(1) kcal/mol) by heterolytic cleavage of H2 with
      Et3N in CH3CN. The transfer of H(-) from 1a to 1-(1
      phenylethylidene)pyrrolidinium is remarkably fast (kH(-) = 3.5(1) * 10(5) M(-1)
      s(-1)), making 1a a very efficient catalyst for the ionic hydrogenation of
      iminium cations. The pKa of 1a in CH3CN has been measured as 30.3(2) with (tert
      butylimino)tris(pyrrolidino)phosphorane (12), and the rate constant for H(+)
      transfer from 1a to 12 has been estimated (kH(+) = 5(1) * 10(-4) M(-1) s(-1))
      from the half-life of the equilibration. Thus, 1a is a poor H(+) donor both
      thermodynamically and kinetically. However, 1a transfers H* to TEMPO smoothly,
      forming a stable Rh(II) radical Cp*Rh(2-(2-pyridyl)phenyl)* (14a) that can
      activate H2 at room temperature and 1 atm. The metalloradical 14a has a g value
      of 2.0704 and undergoes reversible one-electron reduction at -1.85 V vs Fc(+)/Fc
      in benzonitrile, implying a bond-dissociation enthalpy for the Rh-H bond of 1a of
      58.2(3) kcal/mol--among the weakest Rh(III)-H bonds reported. The transfer of H*
      from 1a to Ar3C* (Ar = p-(t)BuC6H4) is fast, with kH* = 1.17(3) * 10(3) M(-1) s(
      1). Thus, 1a is a good H(-) and H* donor but a poor H(+) donor, a combination
      that reflects the high energy of the Rh(I) anion [Cp*Rh(2-(2-pyridyl)phenyl)](-).

PMID- 24666138
TI  - Modeling studies on the structural determinants for the DAG/phorbol ester binding
      to C1 domain.
AB  - C1 domains are small zinc-binding structural units of approximately 50 amino
      acids, originally discovered as lipid-binding modules in protein kinase C (PKC)
      isoforms. C1 domains that bind and respond to the DAG/phorbol ester are termed as
      typical, and those that do not respond to DAG/phorbol ester are termed as
      atypical. To design molecules targeting a specific C1 domain for regulating a
      specific disease state, it is important to understand the factors that make a C1
      domain responsive to DAG/phorbol ester. Here, we determined the volume and
      surface area of the ligand-binding site for all known C1 domains. No correlation
      was found between the volume/surface area of ligand-binding site and the
      DAG/phorbol ester-binding affinity. Solvated molecular dynamics simulation
      reveals that the presence of water molecules affects the flexibility of the
      ligand-binding site. Contributions of the binding site residues, their
      orientations, and the membrane lipids on the responsiveness of a C1 domain
      towards DAG/phorbol ester have been discussed. 

PMID- 24666139
TI  - Impact of adherence to treatment with fluticasone propionate/salmeterol in asthma
      patients.
AB  - OBJECTIVE: Low adherence with asthma treatment may be associated with suboptimal
      outcomes and hence create a treatment gap in the real-life setting. The objective
      of this study was to assess the long-term association between adherence to
      treatment with fixed-dose fluticasone propionate/salmeterol (FSC) and the risk of
      exacerbations and health care utilization in patients with asthma. RESEARCH
      DESIGN AND METHODS: Observational single cohort study utilizing the Quebec Health
      Insurance databases. All patients (age >12 years) with a diagnosis of asthma
      (ICD9-CM 493.xx) between 2001 and 2010 were entered into the study cohort at the
      time of their first prescription for FSC at any dose. Follow-up continued to the
      last known claim or death. Adherence to treatment was ascertained as compliance
      (medication possession ratio >=80%) and persistence (absence of treatment gap
      >=30 days). MAIN OUTCOME MEASURES: Outcomes assessed were exacerbations defined
      as one of the following: use of oral corticosteroid (OCS), emergency room (ER)
      visit for asthma or hospitalization for asthma. Asthma related health care
      resource utilizations ascertained were number of prescription claims for rescue
      medications, ER visits, hospitalizations, intensive care unit (ICU) stay,
      intubations, and general practitioner (GP) and respirologist visits. RESULTS: A
      total of 19,126 patients were included in the study. The proportion of compliant
      and persistent patients were 42.7% and 29.3% respectively. Multivariate logistic
      regression analyses showed a significantly reduced adjusted odds of exacerbations
      for compliant (OR = 0.48; 95% CI: 0.44-0.54) and persistent patients (OR = 0.42;
      95% CI: 0.38-0.48). Similarly, significantly lower rates of health care
      utilization were observed for compliant and persistent patients. CONCLUSIONS: The
      results of this large population-based study have shown that increased adherence
      to treatment with FSC is associated with lower risk for exacerbations, lower
      rescue medication use and lower health care utilization in asthma patients.
      Despite the typical limitations of an administrative database study including
      validity of the diagnosis, the fact that compliance and persistence are
      calculated based on filled claims which does not guarantee that the patients
      actually took their medications, and the absence of clinical and laboratory data,
      the findings have implications for physician and patient awareness of the
      importance of adherence in the management of asthma.

PMID- 24666140
TI  - Factors related to the return to work potential in persons with severe mental
      illness.
AB  - OBJECTIVE: This cross-sectional study aimed at investigating the relationship
      between the return to work potential, according to the Worker Role Interview
      (WRI) assessment, and clinical characteristics and level of empowerment and
      occupational engagement among persons with severe mental illness who express
      their own interest in working. METHODS: 120 participants entered the study. The
      WRI, the Brief Psychiatric and Rating Scale, a sociodemographic questionnaire,
      the Empowerment Scale, and the Profiles of Occupational Engagement in Severe
      mental illness were used for data collection. Correlation and regression analyses
      were used for statistics. RESULTS: The return to work potential was significantly
      associated with having fewer symptoms, rehabilitation support or productive
      activities, and higher levels of engagement and empowerment. A younger age had an
      inverse relation to the lifestyle component in WRI. Depressive symptoms and
      occupational engagement explained 42% of the variance. CONCLUSIONS: The findings
      support the use of an empowerment approach, taking into account the clients'
      symptoms, age, and time use. In addition, involvement in vocational support and
      productive activities may be advantageous early on in the recovery process.

PMID- 24666141
TI  - Are we all equal at death?: death competence in municipal cemetery management.
AB  - Managers of local government cemeteries should balance social and cultural
      expectations with fiscal responsibility and when they do so they demonstrate
      death competence in cemetery management. This study reviews the cultural and
      social equity aspects of the consumption of cemetery services and develops tools
      to take into account social equity and cultural concerns for public sector
      cemetery managers. Cemetery demand and pricing models are developed and applied
      to the case of Austin, Texas. These models enhance the estimation of demand by
      taking into account cultural factors and contextualize pricing in terms of social
      equity concerns. 

PMID- 24666142
TI  - Content and face validity of the marwitmeuser caregiver grief inventory (short
      form) in African American caregivers.
AB  - There may be cultural differences in the experience of predeath grief in African
      American (AA)/Black caregivers for persons with Alzheimers disease (AD). The most
      commonly used screening tool, the Marwit and Meuser Caregiver Grief Inventory
      Short Form (MMCGI-SF), was developed from focus groups with primarily
      Caucasian/White caregivers. Interviews were held with 19 AA spouse and adult
      child caregivers for persons with mild, moderate, and severe AD, and data were
      coded and compared with scale items on the MCMGI-SF to assess validity. Results
      from this study provide evidence for content and face validity of the MMCGI-SF
      for use in AA caregivers. 

PMID- 24666143
TI  - Experiences of african american parents following perinatal or pediatric death: a
      literature review.
AB  - A child's death is one of life's most difficult experiences. Little is known
      about the unique factors that influence the grief experience for bereaved African
      American parents. Through an integrative review of 10 publications, the authors
      describe the grief responses, outcomes, and implications for African American
      parents who experience the death of a child. Four themes emerged: (a) emotional
      response to loss; (b) factors that added to the burden of loss; (c) coping
      strategies; and (d) health consequences of grief. Healthcare providers,
      administrators, and policymakers should be sensitive to the unique needs of
      African American parents following a child's death. 

PMID- 24666144
TI  - Can a function-based therapy for spousally bereaved seniors accrue benefits in
      both functional and emotional domains?
AB  - Late-life spousal bereavement has detrimental effects in daily functioning and
      emotional distress. This study tested the hypothesis that a therapy based
      exclusively upon functioning issues (sleep and daily lifestyle regularity) would
      accrue benefits in both functional and emotional domains. A comparison was made
      with a control therapy that concentrated on emotional issues, and specifically
      avoided discussing sleep or lifestyle regularity. Thirty-eight spousally bereaved
      seniors were randomly assigned to either functional or control therapy.
      Assessments were made before, during, and after a 6-month, 10-session individual
      therapy. The functional therapy assisted in both functional and emotional domains
      and the hypothesis was confirmed. 

PMID- 24666145
TI  - Suicidal and online: how do online behaviors inform us of this high-risk
      population?
AB  - To assist suicide prevention we need a better understanding of how suicidal
      individuals act in their environment, and the online world offers an ideal
      opportunity to examine daily behaviors. This anonymous survey (N = 1,016)
      provides first-of-its-kind empirical evidence demonstrating suicide-risk people
      (n = 290) are unique in their online behaviors. Suicidal users reported more time
      online, greater likelihood of developing online personal relationships, and
      greater use of online forums. In addition, suicide-risk women reported more time
      browsing/surfing and social networking. The authors conclude that suicide
      prevention efforts should respond to suicide-risk users' greater demands for
      online interpersonal communications.

PMID- 24666146
TI  - Predictors of grief in bereaved family caregivers of person's with Alzheimer's
      disease: a prospective study.
AB  - The purpose of this prospective study was to identify factors in 66 spouses and
      adult child caregivers of person's with Alzheimer's disease prior to the death
      that predicted higher levels of grief in bereavement. A hierarchical regression
      model was tested. Predeath grief, dysfunctional coping, depression, social
      support, and decreased positive states of mind explained 54.7% of the variance in
      postdeath grief. Factors that contributed significantly to postdeath grief
      included predeath grief and depression. Results from this study indicate that
      risk factors for postdeath grief can be predicted prior to the death. 

PMID- 24666147
TI  - Changes in parental self-identity following the death of a child to cancer.
AB  - This study explored parental self-identity at 6, 12, and 18 months following the
      death of a child to cancer. Semi-structured interviews were analyzed using
      qualitative methodology. Two patterns of parental self-identity emerged: identity
      reintegration, characterized by 6 associated themes (e.g., positive reframing,
      focusing on surviving children); and identity disintegration, characterized by 7
      associated themes (e.g., negative perceptions of social support, self-destructive
      thoughts and behaviors). Patterns were stable from 6 to 12 months, but a shift
      towards identity disintegration was observed at 18 months. These findings suggest
      a need to support bereaved parents' well-being beyond the first year post-death. 

PMID- 24666148
TI  - Terror management theory applied clinically: implications for existential
      integrative psychotherapy.
AB  - Existential psychotherapy and Terror Management Theory (TMT) offer explanations
      for the potential psychological effects of death awareness, although their
      respective literatures bases differ in clarity, research, and implications for
      treating psychopathology. Existential therapy is often opaque to many therapists,
      in part due to the lack of consensus on what constitutes its practice, limited
      published practical examples, and few empirical studies examining its efficacy.
      By contrast, TMT has an extensive empirical literature base, both within social
      psychology and spanning multiple disciplines, although previously unexplored
      within clinical and counseling psychology. This article explores the implications
      of a proposed TMT integrated existential therapy (TIE), bridging the gap between
      disciplines in order to meet the needs of the aging population and current
      challenges facing existential therapists. 

PMID- 24666149
TI  - Self-related consequences of death fear and death denial.
AB  - This study explores self-related outcomes (e.g., esteem, self-concept clarity,
      existential well-being) as a function of the interaction between self-reported
      levels of death fear and death denial. Consistent with the idea that positive
      existential growth can come from individuals facing, rather than denying, their
      mortality (Cozzolino, 2006 ), the authors observed that not fearing and denying
      death can bolster important positive components of the self. That is, individuals
      low in death denial and death fear evidenced an enhanced self that is valued,
      clearly conceived, efficacious, and that has meaning and purpose. 

PMID- 24666150
TI  - Beyond the Paleolithic prescription: commentary.

PMID- 24666151
TI  - Is high cut-off hemodialysis effective in myeloma kidney?

PMID- 24666152
TI  - Hematology clinic. Sickle cell disease.

PMID- 24666153
TI  - Doxorubicin alters the mitochondrial dynamics machinery and mitophagy in the
      liver of treated animals.
AB  - Doxorubicin (Dox) is an effective chemotherapeutic agent, but known to cause
      cardiac and hepatic toxicity. Mechanisms of toxicity have not been clearly
      identified, but shown to involve oxidative stress and mitochondrial dysfunction.
      However, antioxidant supplementation has only shown modest protection from Dox
      induced toxicity in clinical trials. Therefore, further research is required to
      discern alternative mechanisms that may also play an important role in Dox
      induced toxicity. Thus, we aimed to investigate the role of mitochondrial fusion
      and fission in Dox-induced hepatic toxicity, which has not yet been investigated.
      Six-week-old male F344 rats were injected IP with 20 mg/kg of Dox or saline. Once
      administered, both groups of animals were fasted with no food or water until
      sacrifice 24 h later. Dox decreased content of primary regulators of
      mitochondrial fusion (OPA1, MFN1, and MFN2) with no effect on regulators of
      fission (DRP1 and FIS1), thus shifting the balance favoring mitochondrial
      fission. Moreover, it was determined that mitochondrial fission was likely not
      coupled to cell proliferation or cytochrome c release leading to the activation
      of mitochondrial-mediated apoptotic signaling. Rather, mitochondrial fission may
      be coupled to mitophagy and may be an adaptive response to protect against Dox
      induced hepatic toxicity. This is the first study to report the role of altered
      mitochondrial dynamics and mitophagy machinery in Dox-induced hepatic injury.

PMID- 24666155
TI  - Can temporal course of pain determine patient response to specific medication in
      nummular headache?

PMID- 24666154
TI  - Collecting and analyzing DNA evidence from fingernails: a comparative study.
AB  - Forensic practitioners and crime laboratories regularly collect and analyze
      fingernail evidence; however, the best techniques for processing such evidence
      have not been established. In this study, numerous aspects of fingernail evidence
      processing-collection of exogenous cells, transportation, purification of DNA,
      and STR analysis-were analyzed using fingernails harboring applied blood or
      epithelial cells from scratchings. Autosomal STR mixtures resulted when
      fingernails were soaked or swabbed, while scrapings rarely generated mixtures but
      exhibited allelic dropout. Y-STRs yielded single source profiles, with scrapings
      again showing dropout. A silica-based kit extraction recovered significantly more
      exogenous DNA than did organic extraction, neither of which was affected by nail
      polish. Swabbing nails in succession resulted in some cross-contamination from
      exogenous material, while transporting nails together did not, although there was
      loss of exogenous cells. Optimized nail processing produced complete Y-STR
      profiles of male volunteers from female fingernails following scratchings. 

PMID- 24666156
TI  - Advances in bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic respiratory condition primarily
      affecting infants born less than 28 weeks gestational age. BPD and the diagnostic
      criteria that define it have evolved since the initial description of the disease
      more than four decades ago. BPD is one of the most common and serious
      complications of extreme premature birth. Despite advances in neonatal care and
      continued research into therapeutic strategies the incidence of BPD remains
      unchanged. Pharmacologic approaches to the management of BPD include
      methylxanthines, corticosteroids, and vitamin A supplementation. Supportive
      therapies including the increased use of non-invasive ventilation and careful
      oxygen delivery strive to reduce injury inflicted on the developing lung. Stem
      cell-based therapies are a new investigational strategy showing promise for the
      prevention or treatment of BPD. The goal of this review is to highlight the
      evolution of BPD and review current and potential future therapeutic strategies
      for BPD.

PMID- 24666158
TI  - Effect of localized surface-plasmon mode on exciton transport and radiation
      emission in carbon nanotubes.
AB  - We report on a general theoretical approach to study exciton transport and
      emission in a single-walled carbon nanotube (SWNT) in the presence of a localized
      surface-plasmon (SP) mode within a metal nanoparticle interacting via near-field
      coupling. We derive a set of quantum mechanical equations of motion and
      approximate rate equations that account for the exciton, SP, and the
      environmental degrees of freedom. The material equations are complemented by an
      expression for the radiated power that depends on the exciton and SP populations
      and coherences, allowing for an examination of the angular distribution of the
      emitted radiation that would be measured in experiment. Numerical simulations for
      a (6,5) SWNT and cone-shaped Ag metal tip (MT) have been performed using this
      methodology. Comparison with physical parameters shows that the near-field
      interaction between the exciton-SP occurs in a weak coupling regime, with the
      diffusion processes being much faster than the exciton-SP population exchange. In
      such a case, the effect of the exciton population transfer to the MT with its
      subsequent dissipation (i.e., the Forster energy transfer) is to modify the
      exciton steady state distribution while reducing the equilibration time for
      excitons to reach a steady sate distribution. We find that the radiation
      distribution is dominated by SP emission for a SWNT-MT separation of a few tens
      of nanometers due to the fast SP emission rate, whereas the exciton-SP coherences
      can cause its rotation. 

PMID- 24666157
TI  - Discovery, optimization, and characterization of novel D2 dopamine receptor
      selective antagonists.
AB  - The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for
      neuropsychiatric and endocrine disorders. However, clinically approved drugs
      targeting D2 DAR display poor selectivity between the D2 and other receptors,
      especially the D3 DAR. This lack of selectivity may lead to undesirable side
      effects. Here we describe the chemical and pharmacological characterization of a
      novel D2 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5
      receptor selectivity. The final probe 65 was obtained through a quantitative high
      throughput screening campaign, followed by medicinal chemistry optimization, to
      yield a selective molecule with good in vitro physical properties, metabolic
      stability, and in vivo pharmacokinetics. The optimized molecule may be a useful
      in vivo probe for studying D2 DAR signal modulation and could also serve as a
      lead compound for the development of D2 DAR-selective druglike molecules for the
      treatment of multiple neuropsychiatric and endocrine disorders. 

PMID- 24666159
TI  - Giant magnetic anisotropy of transition-metal dimers on defected graphene.
AB  - Continuous miniaturization of magnetic units in spintronics and quantum computing
      devices inspires efforts to search for magnetic nanostructures with giant
      magnetic anisotropy energy (MAE) and high structural stability. Through density
      functional theory calculations, we found that either Pt-Ir or Os-Ru dimer forms a
      stable vertical structure on the defected graphene and possess an MAE larger than
      60 meV, sufficient for room-temperature applications. Interestingly, their MAEs
      can be conveniently manipulated by using an external electric field, which makes
      them excellent magnetic units in spintronics and quantum computing devices. 

PMID- 24666160
TI  - Graphene-supported nanoelectrocatalysts for fuel cells: synthesis, properties,
      and applications.

PMID- 24666161
TI  - Distinct neural specializations for learning to read words and name objects.
AB  - Understanding the neural systems that underpin reading acquisition is key if
      neuroscientific findings are to inform educational practice. We provide a unique
      window into these systems by teaching 19 adults to read 24 novel words written in
      unfamiliar letters and to name 24 novel objects while in an MRI scanner.
      Behavioral performance on trained items was equivalent for the two stimulus
      types. However, componential letter-sound associations were extracted when
      learning to read, as shown by correct reading of untrained words, whereas object
      name associations were holistic and arbitrary. Activity in bilateral anterior
      fusiform gyri was greater during object name learning than learning to read, and
      ROI analyses indicated that left mid-fusiform activity was predictive of success
      in object name learning but not in learning to read. In contrast, activity in
      bilateral parietal cortices was predictive of success for both stimulus types but
      was greater during learning and recall of written word pronunciations relative to
      object names. We argue that mid-to-anterior fusiform gyri preferentially process
      whole items and contribute to learning their spoken form associations, processes
      that are required for skilled reading. In contrast, parietal cortices
      preferentially process componential visual-verbal mappings, a process that is
      crucial for early reading development. 

PMID- 24666162
TI  - Prestimulus interhemispheric coupling of brain rhythms predicts cognitive-motor
      performance in healthy humans.
AB  - Physiological and neuroimaging studies suggest that human actions are
      characterized by time-varying engagement of functional distributed networks
      within the brain. In this study, we investigated whether specific prestimulus
      interhemispheric connectivity, as a measure of synchronized network between the
      two hemispheres, could lead to a better performance (as revealed by RT) in a
      simple visuomotor task. Eighteen healthy adults underwent EEG recording during a
      visual go/no-go task. In the go/no-go task, a central fixation stimulus was
      followed by a green (50% of probability) or red visual stimulus. Participants had
      to press the mouse button after the green stimuli (go trials). Interhemispheric
      coupling was evaluated by the spectral coherence among all the electrodes
      covering one hemisphere and matched with those on the other. The frequency bands
      of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2
      (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). The
      task-related results showed that interhemispheric connectivity decreased in delta
      and increased in alpha band. Furthermore, we observed positive delta and negative
      alpha correlations with the RT; namely, the faster the RT, the lower delta and
      the higher alpha connection between the two hemispheres. These results suggested
      that the best performance is anticipated by the better functional coupling of
      cortical circuits involved during the processing of the sensorimotor information,
      occurring between the two hemispheres pending cognitive go/no-go task. 

PMID- 24666164
TI  - On the utility of positive and negative feedback in a paired-associate learning
      task.
AB  - This study offers a neurophysiological examination of the relationship between
      feedback processing and learning. A two-choice paired-associate learning task
      borrowed and modified from Tricomi and Fiez [Tricomi, E., & Fiez, J. A. Feedback
      signals in the caudate reflect goal achievement on a declarative memory task.
      Neuroimage, 41, 1154-1167, 2008] was employed to examine the mediofrontal
      electrophysiological brain activity associated with the processing of performance
      feedback in a learning task and to elucidate the extent to which the processing
      of the initial informative feedback is related to learning outcomes. Twenty
      participants were tasked with learning to correctly pair 60 novel objects with
      their names by choosing on a trial-by-trial basis between two possible names and
      receiving feedback about the accuracy of their selection. The novel objects were
      presented in three blocks of trials (rounds), each of which presented the same
      set of 60 objects once. The rounds allowed the separation of the initial
      informative feedback in Round 1 from the other feedback stimuli in Rounds 2 and
      3. The results indicated differences in the processing of initial informative and
      proceeding feedback stimuli. More specifically, the difference appeared to be
      driven by the change in the processing of positive feedback. Moreover, very first
      positive feedback provided in association with a particular new object was found
      associated with learning outcomes. The results imply that signs of successful and
      unsuccessful learning may be detected as early as the initial positive feedback
      provided in a learning task. The results suggest that the process giving rise to
      the feedback-related negativity is sensitive to the utility of the feedback and
      that the processing of the first informative positive feedback is associated with
      learning outcomes.

PMID- 24666163
TI  - Perceptual expertise and top-down expectation of musical notation engages the
      primary visual cortex.
AB  - Most theories of visual processing propose that object recognition is achieved in
      higher visual cortex. However, we show that category selectivity for musical
      notation can be observed in the first ERP component called the C1 (measured 40-60
      msec after stimulus onset) with music-reading expertise. Moreover, the C1 note
      selectivity was observed only when the stimulus category was blocked but not when
      the stimulus category was randomized. Under blocking, the C1 activity for notes
      predicted individual music-reading ability, and behavioral judgments of musical
      stimuli reflected music-reading skill. Our results challenge current theories of
      object recognition, indicating that the primary visual cortex can be selective
      for musical notation within the initial feedforward sweep of activity with
      perceptual expertise and with a testing context that is consistent with the
      expertise training, such as blocking the stimulus category for music reading. 

PMID- 24666166
TI  - Conscious and unconscious representations of observed actions in the human motor
      system.
AB  - Action observation activates the observer's motor system. These motor resonance
      responses are automatic and triggered even when the action is only implied in
      static snapshots. However, it is largely unknown whether an action needs to be
      consciously perceived to trigger motor resonance. In this study, we used single
      pulse TMS to study the facilitation of corticospinal excitability (a measure of
      motor resonance) during supraliminal and subliminal presentations of implied
      action images. We used a forward and backward dynamic masking procedure that
      successfully prevented the conscious perception of prime stimuli depicting a
      still hand or an implied abduction movement of the index or little finger. The
      prime was followed by the supraliminal presentation of a still or implied action
      probe hand. Our results revealed a muscle-specific increase of motor facilitation
      following observation of the probe hand actions that were consciously perceived
      as compared with observation of a still hand. Crucially, unconscious perception
      of prime hand actions presented before probe still hands did not increase motor
      facilitation as compared with observation of a still hand, suggesting that motor
      resonance requires perceptual awareness. However, the presentation of a masked
      prime depicting an action that was incongruent with the probe hand action
      suppressed motor resonance to the probe action such that comparable motor
      facilitation was recorded during observation of implied action and still hand
      probes. This suppression of motor resonance may reflect the processing of action
      conflicts in areas upstream of the motor cortex and may subserve a basic
      mechanism for dealing with the multiple and possibly incongruent actions of other
      individuals. 

PMID- 24666165
TI  - ERPs recorded during early second language exposure predict syntactic learning.
AB  - Millions of adults worldwide are faced with the task of learning a second
      language (L2). Understanding the neural mechanisms that support this learning
      process is an important area of scientific inquiry. However, most previous
      studies on the neural mechanisms underlying L2 acquisition have focused on
      characterizing the results of learning, relying upon end-state outcome measures
      in which learning is assessed after it has occurred, rather than on the learning
      process itself. In this study, we adopted a novel and more direct approach to
      investigate neural mechanisms engaged during L2 learning, in which we recorded
      ERPs from beginning adult learners as they were exposed to an unfamiliar L2 for
      the first time. Learners' proficiency in the L2 was then assessed behaviorally
      using a grammaticality judgment task, and ERP data acquired during initial L2
      exposure were sorted as a function of performance on this task. High-proficiency
      learners showed a larger N100 effect to open-class content words compared with
      closed-class function words, whereas low-proficiency learners did not show a
      significant N100 difference between open- and closed-class words. In contrast,
      amplitude of the N400 word category effect correlated with learners' L2
      comprehension, rather than predicting syntactic learning. Taken together, these
      results indicate that learners who spontaneously direct greater attention to open
      rather than closed-class words when processing L2 input show better syntactic
      learning, suggesting a link between selective attention to open-class content
      words and acquisition of basic morphosyntactic rules. These findings highlight
      the importance of selective attention mechanisms for L2 acquisition. 

PMID- 24666167
TI  - Neurophysiological signals of ignoring and attending are separable and related to
      performance during sustained intersensory attention.
AB  - The ability to attend to an input selectively while ignoring distracting
      sensations is thought to depend on the coordination of two processes: enhancement
      of target signals and attenuation of distractor signals. This implies that
      attending and ignoring may be dissociable neural processes and that they make
      separable contributions to behavioral outcomes of attention. In this study, we
      tested these hypotheses in the context of sustained attention by measuring
      neurophysiological responses to attended and ignored stimuli in a noncued,
      continuous, audiovisual selective attention task. We compared these against
      responses during a passive control to quantify effects of attending and ignoring
      separately. In both sensory modalities, responses to ignored stimuli were
      attenuated relative to a passive control, whereas responses to attended stimuli
      were enhanced. The scalp topographies and brain activations of these modulatory
      effects were consistent with the sensory regions that process each modality. They
      also included parietal and prefrontal activations that suggest these effects
      arise from interactions between top-down and sensory cortices. Most importantly,
      we found that both attending and ignoring processes contributed to task accuracy
      and that these effects were not correlated--suggesting unique neural
      trajectories. This conclusion was supported by the novel observation that
      attending and ignoring differed in timing and in active cortical regions. The
      data provide direct evidence for the separable contributions of attending and
      ignoring to behavioral outcomes of attention control during sustained
      intersensory attention.

PMID- 24666168
TI  - From feedback- to response-based performance monitoring in active and
      observational learning.
AB  - Humans can adapt their behavior by learning from the consequences of their own
      actions or by observing others. Gradual active learning of action-outcome
      contingencies is accompanied by a shift from feedback- to response-based
      performance monitoring. This shift is reflected by complementary learning-related
      changes of two ACC-driven ERP components, the feedback-related negativity (FRN)
      and the error-related negativity (ERN), which have both been suggested to signal
      events "worse than expected," that is, a negative prediction error. Although
      recent research has identified comparable components for observed behavior and
      outcomes (observational ERN and FRN), it is as yet unknown, whether these
      components are similarly modulated by prediction errors and thus also reflect
      behavioral adaptation. In this study, two groups of 15 participants learned
      action-outcome contingencies either actively or by observation. In active
      learners, FRN amplitude for negative feedback decreased and ERN amplitude in
      response to erroneous actions increased with learning, whereas observational ERN
      and FRN in observational learners did not exhibit learning-related changes.
      Learning performance, assessed in test trials without feedback, was comparable
      between groups, as was the ERN following actively performed errors during test
      trials. In summary, the results show that action-outcome associations can be
      learned similarly well actively and by observation. The mechanisms involved
      appear to differ, with the FRN in active learning reflecting the integration of
      information about own actions and the accompanying outcomes. 

PMID- 24666169
TI  - Effects of obesity on occupant responses in frontal crashes: a simulation
      analysis using human body models.
AB  - The objective of this study is to investigate the effects of obesity on occupant
      responses in frontal crashes using whole-body human finite element (FE) models
      representing occupants with different obesity levels. In this study, the geometry
      of THUMS 4 midsize male model was varied using mesh morphing techniques with
      target geometries defined by statistical models of external body contour and
      exterior ribcage geometry. Models with different body mass indices (BMIs) were
      calibrated against cadaver test data under high-speed abdomen loading and frontal
      crash conditions. A parametric analysis was performed to investigate the effects
      of BMI on occupant injuries in frontal crashes based on the Taguchi method while
      controlling for several vehicle design parameters. Simulations of obese occupants
      predicted significantly higher risks of injuries to the thorax and lower
      extremities in frontal crashes compared with non-obese occupants, which is
      consistent with previous field data analyses. These higher injury risks are
      mainly due to the increased body mass and relatively poor belt fit caused by soft
      tissues for obese occupants. This study demonstrated the feasibility of using a
      parametric human FE model to investigate the obesity effects on occupant
      responses in frontal crashes. 

PMID- 24666170
TI  - Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier
      discharge plasma generator (PlasmaDerm((r)) VU-2010): results of a monocentric,
      two-armed, open, prospective, randomized and controlled trial (NCT01415622).
AB  - BACKGROUND: Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating
      promising tool in reducing bacteria. OBJECTIVE: We conducted the first clinical
      trial with the novel PlasmaDerm(r) VU-2010 device to assess safety and, as
      secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric
      plasma as add-on therapy against chronic venous leg ulcers. METHODS: From April
      2011 to April 2012, 14 patients were randomized to receive standardized modern
      wound care (n = 7) or plasma in addition to standard care (n = 7) 3* per week for
      8 weeks. The ulcer size was determined weekly (Visitrak(r) , photodocumentation).
      Bacterial load (bacterial swabs, contact agar plates) and pain during and between
      treatments (visual analogue scales) were assessed. Patients and doctors rated the
      applicability of plasma (questionnaires). RESULTS: The plasma treatment was safe
      with 2 SAEs and 77 AEs approximately equally distributed among both groups (P =
      0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma.
      Plasma treatment resulted in a significant reduction in lesional bacterial load
      (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was
      noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively,
      and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) ,
      standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer
      that closed after 7 weeks received plasma. Patients in the plasma group quoted
      less pain compared to the control group. The plasma applicability was not rated
      inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test).
      Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P =
      0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend. CONCLUSION: Cold
      atmospheric plasma displays favourable antibacterial effects. We demonstrated
      that plasma treatment with the PlasmaDerm(r) VU-2010 device is safe and effective
      in patients with chronic venous leg ulcers. Thus, larger controlled trials and
      the development of devices with larger application surfaces are warranted.

PMID- 24666171
TI  - Development of the writing readiness inventory tool in context (WRITIC).
AB  - This article describes the development of the Writing Readiness Inventory Tool in
      Context (WRITIC), a measurement evaluating writing readiness in Dutch
      kindergarten children (5 and 6 years old). Content validity was established
      through 10 expert evaluations in three rounds. Construct validity was established
      with 251 children following regular education. To identify scale constructs,
      factor analysis was performed. Discriminative validity was established by
      examining contrast groups with good (n = 142) and poor (n = 109) performers in
      paper-and-pencil tasks. Content validity was high with 94.4% agreement among the
      experts. Two reliable factors were found in the performance of paper-and-pencil
      tasks with Cronbach's alphas of 0.82 and 0.69 respectively. The contrast groups
      differed significantly in two WRITIC subdomains: "Sustained attention" and "Task
      performance". Our findings indicated that the WRITIC is feasible for use in the
      classroom.

PMID- 24666172
TI  - Relationships among family participation, team support, and intensity of early
      intervention services.
AB  - AIMS: In America, children with disabilities and their families may receive early
      intervention (EI) services under the Individuals with Disabilities Education
      Improvement Act (IDEA). The IDEA mandates that decisions on service delivery are
      based on the needs of the child and family. It is unclear how decisions on
      intensity of services are made in EI. The purpose of this study was to determine
      whether parent participation and team support are determinants of the
      recommendation for intensity of service at the initial Individualized Family
      Service Planning (IFSP) meeting. METHODS: The participants were 63 parents of
      children 2-33 months of age and 74 professionals. The first author observed all
      IFSP meetings and completed the Parent Participation Measure. Following the
      meeting, parents completed a demographic form, the Ages and Stages Questionnaire,
      and the Family Needs Survey. The recommended intensity of service was recorded.
      RESULTS AND CONCLUSIONS: Parent participation and team support were not
      significant determinants of intensity of EI service after controlling for child
      development and family needs (R2 = 0.145, p = .14). The recommended intensity of
      service was 240 min per month for 57% of the families suggesting that factors
      other than parent participation and team support influenced the decision on
      intensity of service.

PMID- 24666173
TI  - The changes in the expression levels of follicular markers in keratoacanthoma
      depend on the stage: keratoacanthoma is a follicular neoplasm exhibiting
      infundibular/isthmic differentiation without expression of CK15.
AB  - BACKGROUND: Although the precise etiology of keratoacanthoma (KA) is unknown, KA
      is generally assumed to differentiate toward hair follicles based on previous
      studies of experimental carcinogenesis. METHODS: We performed a comprehensive
      immunohistochemical study of various follicular markers in all stages of KA. A
      total of 67 tumors, including 16 early or proliferative stage lesions, 43 well
      developed stage lesions, five regressing stage lesions and three regressed stage
      lesions, were subjected to the analysis. RESULTS: CK15 (clone C8/144B), CK19 and
      CD34 were not expressed at any stage. CK1, CK10, CK16, CK17, CK15 (clone LHK15)
      and calretinin showed dynamic changes in their expression in KA depending on the
      stage. CONCLUSIONS: KA is a follicular neoplasm with infundibular/isthmic (upper
      segmental region of hair follicles) differentiation. It is considered that early
      or proliferative stage tumors show keratin-filled invaginations with infundibular
      differentiation and gradual isthmic differentiation. Well-developed examples of
      KA generally show isthmic differentiation in the whole lesions. The regressed
      stage KAs lose the features of this type of follicular differentiation and show
      epidermal characteristics. No expression of CK15 (clone C8/144B) was observed in
      KAs, although this finding is insufficient to completely rule out the correlation
      between the regression of KA and the hair follicle cycle.

PMID- 24666174
TI  - Lost-to-care and engaged-in-care HIV patients in Leningrad Oblast, Russian
      Federation: barriers and facilitators to medical visit retention.
AB  - Sixty-nine percent of the 1.5 million Eastern Europeans and Central Asians with
      HIV live in the Russian Federation. Antiretroviral therapy (ART) is effective but
      cannot help those who leave treatment. Focus groups with patients who dropped out
      of ART for >=12 months (lost-to-care, LTCs, n = 21) or continued for >=12 months
      (engaged-in-care; EICs; n = 24) were conducted in St. Petersburg. Structural
      barriers included stigma/discrimination and problems with providers and accessing
      treatment. Individual barriers included employment and caring for dependents,
      inaccurate beliefs about ART (LTC only), side-effects, substance use (LTCs,
      present; EICs, past), and depression. Desire to live, social support, and
      spirituality were facilitators for both; EICs also identified positive thinking
      and experiences with ART and healthcare/professionals. Interventions to
      facilitate retention and adherence are discussed. 

PMID- 24666175
TI  - Should target hemoglobin levels in dialysis patients be lowered to 9-10 g/dl?

PMID- 24666176
TI  - Impact of a new levonorgestrel intrauterine system, Levosert((r)), on heavy
      menstrual bleeding: results of a one-year randomised controlled trial.
AB  - OBJECTIVE: To evaluate a new levonorgestrel-releasing intrauterine system (LNG
      IUS) called Levosert((r)) for the treatment of heavy menstrual bleeding (HMB) in
      comparison to the reference product Mirena((r)). METHODS: A multicentre,
      randomised, controlled trial, in non-menopausal women diagnosed with functional
      HMB (defined as menstrual blood loss [MBL] >= 80 mL) randomised to either
      Levosert((r)) or Mirena((r)) and followed for up to one year. MBL was evaluated
      using a validated modified version of the Wyatt pictogram. RESULTS: A total of
      280 women were randomised (141 to Levosert((r)) and 139 to Mirena((r))). During
      the one-year treatment period, both Levosert((r)) and Mirena((r)) dramatically
      decreased MBL and increased haemoglobin and ferritin levels. There were no
      statistically significant differences between Levosert((r)) and Mirena((r))
      regarding any of the parameters evaluated during the study. Similar bleeding
      patterns were observed in both groups. Levosert((r)) was inserted with the same
      ease as Mirena((r)). Both treatments were associated with identical expulsion
      rates and no perforations occurred in either treatment group. CONCLUSION:
      Levosert((r)), a new LNG-IUS designed to release the same daily amount of LNG as
      Mirena((r)), is highly effective in the treatment of HMB. No differences were
      observed between Levosert((r)) and Mirena((r)) regarding all evaluated outcomes,
      including safety profile.

PMID- 24666177
TI  - 'Part of the job': male-to-male sexual experiences and abuse of young men working
      as 'truck cleaners' along the highways of Pakistan.
AB  - As part of a study on the sexual health and social protection needs of men who
      have sex with men in Pakistan, 11 young men employed as assistants to truckers
      ('truck cleaners') who acknowledged having had sexual experiences with men, were
      interviewed and their social background and sexual initiation and their
      subsequent sexual lives were explored. For most truck cleaners, the first
      instance of sexual contact between the truck cleaner and the driver was forced
      and happened at an early age. Sex with other men, as well as with women
      (including sex workers) was widely reported. Drug and alcohol use was common.
      There is strong potential for HIV and STIs to spread through these sexual
      networks. Measures to prevent young men from entering into a career as truck
      helpers should be considered, as well as interventions to improve the health and
      social situation of those already employed. 

PMID- 24666178
TI  - Molecular and cellular mechanisms of development underlying  congenital diseases.
AB  - In the last several decades, developmental biology has clarified the molecular
      mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated
      that the "tool-kit genes" essential for regulating developmental processes are
      not only highly conserved among species, but are also used as systems at various
      times and places in an organism to control distinct developmental events.
      Therefore, mutations in many of these tool-kit genes may cause congenital
      diseases involving morphological abnormalities. This link between genes and
      abnormal morphological phenotypes underscores the importance of understanding how
      cells behave and contribute to morphogenesis as a result of gene function. Recent
      improvements in live imaging and in quantitative analyses of cellular dynamics
      will advance our understanding of the cellular pathogenesis of congenital
      diseases associated with aberrant morphologies. In these studies, it is critical
      to select an appropriate model organism for the particular phenomenon of
      interest.

PMID- 24666179
TI  - Ofatumumab monotherapy in relapsed/refractory mantle cell lymphoma--a phase II
      trial.

PMID- 24666180
TI  - Losses related to everyday occupations for adults affected by mental illness.
AB  - OBJECTIVE: This paper presents findings from a larger study that explored losses
      from mental illness. Losses associated with occupations--a key theme from this
      participatory action research study--are the focus of this paper. METHODS: Semi
      structured in-depth interviews were carried out with 16 people who had been
      diagnosed with a mental illness and attended a community mental health centre.
      Interviews were transcribed verbatim and thematically analysed, guided by
      processes proposed by Dey. RESULTS: Numerous losses influenced participants'
      ability to initiate or engage in daily occupations. Some losses perpetuated
      further loss, at times with profound consequences, such as the loss of a house
      following a loss of work. Engaging in chosen occupations was often described as a
      longer-term goal or something participants did infrequently, due to losses such
      as motivation, energy, or normal sleeping patterns. The desire to work and
      participate in everyday occupations was emphasized and its benefits highlighted,
      despite previous difficulties. CONCLUSIONS: Implications for occupational
      therapists include the importance of exploring, validating, and responding to
      losses when these are shared, and being aware of and striving to support people
      experiencing losses in the areas of work, motivation, sleep patterns, and energy,
      which were perceived as especially challenging for participants in this study.

PMID- 24666181
TI  - Impact of adherence to treatment with tiotropium and fluticasone
      propionate/salmeterol in chronic obstructive pulmonary diseases patients.
AB  - OBJECTIVE: Poor adherence to treatment may contribute to the treatment gap in
      chronic obstructive pulmonary diseases (COPD). The aim of the current study was
      to describe the association between adherence to treatment and the risk of COPD
      moderate (ME) and severe (SE) exacerbations, and health care utilization.
      RESEARCH DESIGN AND METHODS: Observational single cohort study utilizing the
      Quebec Provincial Health Insurance databases. All patients older than 40 years
      with a diagnosis of COPD between 2001 and 2010 were entered in the study cohort
      at the time of their first prescription for tiotropium (TIO) alone or co
      administered with fluticasone propionate/salmeterol (TIO + FSC). Follow-up
      continued to the last known claim or death. Adherence was measured by the
      medication possession ratio (MPR) >=80% and persistence defined as no treatment
      gap >=30 days. MAIN OUTCOME MEASURES: ME was defined as use of an oral
      corticosteroid or antibiotic, SE as COPD related hospitalization or an emergency
      room (ER) visit. COPD related health care resource utilization ascertained was
      prescription of rescue medications, ER visits, hospitalizations, intensive care
      unit (ICU) admissions, intubations, and general practitioner (GP) and
      respirologist visits. RESULTS: There were 23,707 patients included in this study.
      Compliance and persistence with TIO for monotherapy patients were 61.1% and 47.6%
      respectively. For patients treated with TIO + FSC, compliance and persistence for
      TIO were 62.9% and 45.3% respectively, and for FSC they were 35.4% and 33.0%.
      Multivariate analyses showed a significant (P < 0.001) adjusted odds ratios for
      ME (OR(ME)) and SE (OR(SE)) for TIO compliant vs. non-compliant patients (TIO:
      OR(ME) = 0.543, OR(SE) = 0.712; TIO + FSC: OR(ME) = 0.436, OR(SE) = 0.570).
      Similarly for FSC compliance: OR(ME) = 0.546; OR(SE) = 0.749. Similar results
      were observed for persistence. Compliance and persistence with TIO and FSC were
      associated with significantly reduced rates of health care utilization.
      CONCLUSIONS: Despite the typical limitations of an administrative database study,
      the results of this large population-based study have shown that reduced
      adherence to treatment with TIO and FSC is associated with increased risk for
      exacerbations and higher health care utilization in COPD patients.

PMID- 24666183
TI  - Beyond the Paleolithic prescription: authors' reply to commentary.

PMID- 24666182
TI  - Ligand-enabled gamma-C-H olefination and carbonylation: construction of beta
      quaternary carbon centers.
AB  - Monoselective gamma-C-H olefination and carbonylation of aliphatic acids has been
      accomplished by using a combination of a quinoline-based ligand and a weakly
      coordinating amide directing group. The reaction provides a new route for
      constructing richly functionalized all-carbon quaternary carbon centers at the
      beta-position of aliphatic acids. 

PMID- 24666184
TI  - Single cell-derived clones from human adipose stem cells present different
      immunomodulatory properties.
AB  - Human adipose mesenchymal stem cells are a heterogeneous population, where cell
      cultures derived from single-cell-expanded clones present varying degrees of
      differential plasticity. This work focuses on the immunomodulatory/anti
      inflammatory properties of these cells. To this end, five single-cell clones were
      isolated (generally called 1.X and 3.X) from two volunteers. Regarding the
      expression level of the lineage-characteristic surface antigens, clones 1.10 and
      1.22 expressed the lowest amounts, while clones 3.10 and 3.5 expressed more CD105
      than the rest and clone 1.7 expressed higher amounts of CD73 and CD44. Regarding
      cytokine secretion, all clones were capable of spontaneously releasing high
      levels of interleukin (IL)-6 and low to moderate levels of IL-8. These
      differences can be explained in part by the distinct methylation profile
      exhibited by the clones. Furthermore, and after lipopolysaccharide stimulation,
      clone 3.X produced the highest amounts of proinflammatory cytokines such as IL
      1beta, while clones 1.10 and 1.22 highly expressed IL-4 and IL-5. In co-culture
      experiments, clones 1.X are, together, more potent inhibitors than clones 3.X for
      proliferation of total, CD3(+) T, CD4(+) T and CD8(+) T lymphocytes and natural
      killer (NK) cells. The results of this work indicate that the adipose stem cell
      population is heterogeneous in cytokine production profile, and that isolation,
      characterization and selection of the appropriate cell clone is a more exact
      method for the possible treatment of different patients or pathologies. 

PMID- 24666188
TI  - Highly efficient and scalable synthesis of clionamine D.
AB  - Herein we describe an efficient and scalable synthesis of clionamine D (4), a
      special member with autophagy bioactivity and an unprecedented spirobislactone
      side chain in the novel aminosteroid clionamines. This synthesis features a quick
      access to alpha-methylene-gamma-lactone 8 and a Mn(OAc)3-mediated radical [3 + 2]
      reaction to assemble the unique spirobislactone unit. Clionamine D (4) can also
      serve as a key synthetic precursor to other clionamine members. 

PMID- 24666187
TI  - An inter-laboratory comparison of PNH clone detection by high-sensitivity flow
      cytometry in a Russian cohort.
AB  - OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem
      cell disorder characterized by partial or absolute deficiency of
      glycophosphatidyl-inositol (GPI) anchor-linked surface proteins on blood cells. A
      lack of precise diagnostic standards for flow cytometry has hampered useful
      comparisons of data between laboratories. We report data from the first study
      evaluating the reproducibility of high-sensitivity flow cytometry for PNH in
      Russia. METHODS: PNH clone sizes were determined at diagnosis in PNH patients at
      a central laboratory and compared with follow-up measurements in six laboratories
      across the country. Analyses in each laboratory were performed according to
      recommendations from the International Clinical Cytometry Society (ICCS) and the
      more recent 'practical guidelines'. Follow-up measurements were compared with
      each other and with the values determined at diagnosis. RESULTS: PNH clone size
      measurements were determined in seven diagnosed PNH patients (five females, two
      males: mean age 37 years); five had a history of aplastic anemia and three (one
      with and two without aplastic anemia) had severe hemolytic PNH and elevated
      plasma lactate dehydrogenase. PNH clone sizes at diagnosis were low in patients
      with less severe clinical symptoms (0.41-9.7% of granulocytes) and high in
      patients with severe symptoms (58-99%). There were only minimal differences in
      the follow-up clone size measurement for each patient between the six
      laboratories, particularly in those with high values at diagnosis. CONCLUSIONS:
      The ICCS-recommended high-sensitivity flow cytometry protocol was effective for
      detecting major and minor PNH clones in Russian PNH patients, and showed high
      reproducibility between laboratories.

PMID- 24666189
TI  - Rationale and timing of perioperative chemotherapy for upper-tract urothelial
      carcinoma.
AB  - Radical surgery alone for high-risk upper-tract urothelial carcinoma (UTUC) is
      often inadequate for long-term cancer control. Numerous studies implicate failure
      presumably attributable to metastatic disease. Therefore, multimodal therapy by
      way of perioperative chemotherapy is integral to improve cancer outcomes and
      disease-specific survival. Despite this apparent reality, there is lack of
      consensus regarding which patients will need additional therapy, optimal timing
      for delivery of agents, and specific regimens to be utilized. Progress is being
      made, however, to explore these issues both by extrapolation from the bladder
      cancer literature as well as studying outcomes from retrospective UTUC series.
      Prospectively accruing studies for both neoadjuvant and adjuvant chemotherapy
      will likely mature in the next 5 years thereby providing higher level data to
      better guide standard of care. 

PMID- 24666186
TI  - Allosteric inhibition of human factor XIa: discovery of monosulfated benzofurans
      as a class of promising inhibitors.
AB  - Factor XIa (fXIa) is being recognized as a prime target for developing safer
      anticoagulants. To discover synthetic, small, allosteric inhibitors of fXIa, we
      screened an in-house, unique library of 65 molecules displaying many distinct
      scaffolds and varying levels of sulfation. Of these, monosulfated benzofurans
      were the only group of molecules found to inhibit fXIa (~100% efficacy) and led
      to the identification of monosulfated trimer 24 (IC50 0.82 MUM) as the most
      potent inhibitor. Michaelis-Menten kinetics studies revealed a classic
      noncompetitive mechanism of action for 24. Although monosulfated, the inhibitors
      did not compete with unfractionated heparin alluding to a novel site of
      interaction. Fluorescence quenching studies indicated that trimer 24 induces
      major conformational changes in the active site of fXIa. Docking studies
      identified a site near Lys255 on the A3 domain of fXIa as the most probable site
      of binding for 24. Factor XIa devoid of the A3 domain displayed a major defect in
      the inhibition potency of 24 supporting the docking prediction. Our work presents
      the sulfated benzofuran scaffold as a promising framework to develop allosteric
      fXIa inhibitors that likely function through the A3 domain. 

PMID- 24666190
TI  - Partial anhidrosis demonstrated by Q-SART in a patient with a novel mutation in
      the EDARADD gene.

PMID- 24666191
TI  - Systolic fluid-structure interaction model of the congenitally bicuspid aortic
      valve: assessment of modelling requirements.
AB  - A transient fluid-structure interaction (FSI) model of a congenitally bicuspid
      aortic valve has been developed which allows simultaneous calculation of fluid
      flow and structural deformation. The valve is modelled during the systolic phase
      (the stage when blood pressure is elevated within the heart to pump blood to the
      body). The geometry was simplified to represent the bicuspid aortic valve in two
      dimensions. A congenital bicuspid valve is compared within the aortic root only
      and within the aortic arch. Symmetric and asymmetric cusps were simulated, along
      with differences in mechanical properties. A moving arbitrary Lagrange-Euler mesh
      was used to allow FSI. The FSI model requires blood flow to induce valve opening
      and induced strains in the region of 10%. It was determined that bicuspid aortic
      valve simulations required the inclusion of the ascending aorta and aortic arch.
      The flow patterns developed were sensitive to cusp asymmetry and differences in
      mechanical properties. Stiffening of the valve amplified peak velocities, and
      recirculation which developed in the ascending aorta. Model predictions
      demonstrate the need to take into account the category, including any existing
      cusp asymmetry, of a congenital bicuspid aortic valve when simulating its fluid
      flow and mechanics. 

PMID- 24666192
TI  - The power of contextual effects in forensic anthropology: a study of biasability
      in the visual interpretations of trauma analysis on skeletal remains.
AB  - The potential for contextual information to bias assessments in the forensic
      sciences has been demonstrated, in several forensic disiplines. In this paper,
      biasability potential within forensic anthropology was examined by analyzing the
      effects of external manipulations on judgments and decision-making in visual
      trauma assessment. Three separate websites were created containing fourteen
      identical images. Participants were randomly assigned to one website. Each
      website provided different contextual information, to assess variation of
      interpretation of the same images between contexts. The results indicated a
      higher scoring of trauma identification responses for the Mass grave context.
      Furthermore, a significant biasing effect was detected in the interpretation of
      four images. Less experienced participants were more likely to indicate presence
      of trauma. This research demonstrates bias impact in forensic anthropological
      trauma assessments and highlights the importance of recognizing and limiting
      cognitive vulnerabilities that forensic anthropologists might bring to the
      analysis. 

PMID- 24666193
TI  - Linear absorption and two-dimensional infrared spectra of N-methylacetamide in
      chloroform revisited: polarizability and multipole effects.
AB  - The effect of solvent polarizability and multipole effects on the amide I
      vibrational spectra of a peptide unit is investigated. Four molecular dynamics
      force fields of increasing complexity for the solvent are used to model both the
      linear absorption and two-dimensional infrared spectra. It is observed that, at
      least in chloroform solution, the predicted solvent shift is considerably
      improved when accounting for the polarizabiltiy and multipole effects. The latter
      are typically connected with halogen bonding. Significant deviations are still
      observed for more sensitive line shape parameters such as the spectral width and
      line skewness. However, the findings demonstrate that previously observed
      deviations have an origin in the force field treatment rather than in the
      electrostatic mapping procedure frequently employed to simulate linear absorption
      and two-dimensional infrared spectroscopy. 

PMID- 24666194
TI  - Expression of lymphatic markers in angiokeratomas.
AB  - BACKGROUND: The term angiokeratoma refers to a group of unrelated diseases with
      similar histopathologic features. Four clinical variants of angiokeratoma have
      been described. However, it is not known whether some variants of angiokeratoma
      are of lymphatic origin, and an immunohistochemical study of lymphatic markers
      has not been previously performed. METHODS: We performed an immunohistochemical
      study of angiokeratomas using lymphatic markers. Fifteen cases of angiokeratoma
      corporis diffusum, 10 cases of Fordyce angiokeratoma, 10 cases of Mibelli
      angiokeratoma and 10 cases of solitary angiokeratoma were examined by
      immunohistochemical analysis using CD31, D2-40, Prox1 and Wilms' tumor 1 (WT-1).
      RESULTS: The vessels of angiokeratoma corporis diffusum, Fordyce angiokeratoma
      and solitary angiokeratoma were usually focally positive for D2-40 and positive
      for Prox1, whereas the vessels of Mibelli angiokeratoma were negative for D2-40
      and positive for Prox1. CONCLUSIONS: The results suggest lymphatic derivation of
      angiokeratoma corporis diffusum, Fordyce angiokeratoma and solitary
      angiokeratoma. However, the derivation of Mibelli angiokeratoma could not be
      determined based on the present immunohistochemical results.

PMID- 24666195
TI  - The effect of friendly touch on delay-of-gratification in preschool children.
AB  - Physical touch has many documented benefits, but past research has paid little
      attention to the effects of touch on children's development. Here, we tested the
      effect of touch on children's compliance behaviour in a modified delay-of
      gratification task. Forty children (M = 59 months) were randomly assigned to a
      touch or no touch group. Children in the intervention condition received a
      friendly touch on the back while being told that they should wait for permission
      to eat a candy. Results showed that children in the touch condition waited an
      average of two minutes longer to eat the candy than children in the no touch
      condition. This finding has implications for the potential of using touch to
      promote positive behaviours in children.

PMID- 24666196
TI  - Unusual cause of the headache and hypophyseal insufficient: intrasphenoidal
      encephalocele.

PMID- 24666197
TI  - Work and everyday activities: experiences from two interventions addressing
      people with common mental disorders.
AB  - OBJECTIVE: Lengthy sick leave makes demands on work ability enhancing
      interventions in primary health care. Problem-based method (PBM) and cognitive
      behavioural therapy (CBT) are interventions aimed at people with common mental
      disorders. This study aimed to describe how individuals experienced interventions
      and the impact the interventions had on the individuals' ability to work and
      perform other everyday activities. METHOD: Fourteen women and two men, eight each
      from two interventions, were interviewed. The interviews were analysed using
      qualitative content analysis. RESULTS: The analysis revealed one overarching
      theme: "Reaching safe ground or continuing to seek help". Four categories were
      identified: "From being passive to making one's own efforts in the rehabilitation
      process", "Being stuck on a treadmill or daring to change", "Evolving from
      routine to more aware behaviour", and "Fitting in or not fitting in with
      workplace situations". CONCLUSIONS: According to the participants, experiences
      from both PBM and CBT had a positive impact on their ability to work and perform
      other everyday activities in a more sustainable way. Reflecting on behaviour and
      achieving limiting strategies were perceived as helpful in both interventions,
      although varying abilities to incorporate strategies were described. In general,
      the results support the use of active coping-developing interventions rather than
      passive treatments.

PMID- 24666198
TI  - Introduction to single molecule imaging and mechanics: seeing and touching
      molecules one at a time.

PMID- 24666200
TI  - HLA-partially matched cellular therapy (stem-cell microtransplantation) for acute
      myeloid leukaemia: description of four cases.

PMID- 24666201
TI  - Sex differentials in the uptake of antiretroviral treatment in Zambia.
AB  - This study explores socio-structural factors that influence uptake of
      antiretroviral treatment (ART) in Zambia and assess differences between men and
      women. We conducted a case-control study nested in a community- and health
      facility-based survey, between September 2010 and February 2011. Cases were
      defined as HIV-positive individuals who, while eligible, never started ART and
      controls were HIV-positive individuals who were on ART. Cases and controls were
      matched by place of residence. We performed a conditional logistic regression
      analysis using a discrete logistic model stratified by sex. Overall, a
      significantly larger proportion of men (32.7%) than women (25.6%) did not uptake
      ART (Pearson chi(2) = 5.9135; p = 0.015). In the crude analysis, poor health
      status and low self-efficacy were common factors associated with non-uptake in
      both sexes. After adjusting for covariates, men were more likely than women to
      refuse ART even though men's self-rated health was lower than women's. In
      general, the adjusted analysis suggests that HIV status disclosure affects uptake
      in both sexes but women's uptake of ART is largely hampered by poverty-related
      factors while for men, side effects and social pressure, probably associated with
      masculinity, are more important barriers. Alarmingly men's health seems to
      deteriorate until they start treatment, in contrast to women. Understanding
      gender differences in uptake and attitudes to ART is a crucial component to
      providing effective and appropriate health care to both men and women living with
      HIV/AIDS in Zambia.

PMID- 24666199
TI  - Single-molecule fluorescence and in vivo optical traps: how multiple dyneins and
      kinesins interact.

PMID- 24666202
TI  - Epicardium is required for sarcomeric maturation and cardiomyocyte growth in the
      ventricular compact layer mediated by transforming growth factor beta and
      fibroblast growth factor before the onset of coronary circulation.
AB  - The epicardium, which is derived from the proepicardial organ (PE) as the third
      epithelial layer of the developing heart, is crucial for ventricular
      morphogenesis. An epicardial deficiency leads to a thin compact layer for the
      developing ventricle; however, the mechanisms leading to the impaired development
      of the compact layer are not well understood. Using chick embryonic hearts, we
      produced epicardium-deficient hearts by surgical ablation or blockade of the
      migration of PE and examined the mechanisms underlying a thin compact myocardium.
      Sarcomeric maturation (distance between Z-lines) and cardiomyocyte growth (size)
      were affected in the thin compact myocardium of epicardium-deficient ventricles,
      in which the amounts of phospho-smad2 and phospho-ERK as well as expression of
      transforming growth factor (TGF)beta2 and fibroblast growth factor (FGF)2 were
      reduced. TGFbeta and FGF were required for the maturation of sarcomeres and
      growth of cardiomyocytes in cultured ventricles. In ovo co-transfection of
      dominant negative (dN)-Alk5 (dN-TGFbeta receptor I) and dN-FGF receptor 1 to
      ventricles caused a thin compact myocardium. Our results suggest that immature
      sarcomeres and small cardiomyocytes are the causative architectures of an
      epicardium-deficient thin compact layer and also that epicardium-dependent
      signaling mediated by TGFbeta and FGF plays a role in the development of the
      ventricular compact layer before the onset of coronary circulation. 

PMID- 24666203
TI  - Discovery of trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as potent,
      orally bioavailable TGR5 (GPBAR1) agonists: structure-activity relationships,
      lead optimization, and chronic in vivo efficacy.
AB  - Activation of the G-protein coupled receptor (GPCR) Takeda G-protein receptor 5
      (TGR5), also known as G-protein bile acid receptor 1 (GPBAR1), has been shown to
      play a key role in pathways associated with diabetes, metabolic syndrome, and
      autoimmune disease. Nipecotamide 5 was identified as an attractive starting point
      after a high-throughput screen (HTS) for receptor agonists. A comprehensive hit
      to-lead effort culminated in the discovery of 45h as a potent, selective, and
      bioavailable TGR5 agonist to test in preclinical metabolic disease models. In
      genetically obese mice (ob/ob), 45h was as effective as a dipeptidyl peptidase-4
      (DPP-4) inhibitor at reducing peak glucose levels in an acute oral glucose
      tolerance test (OGTT), but this effect was lost upon chronic dosing. 

PMID- 24666205
TI  - Contextually appropriate access to treatment for interpersonal violence.

PMID- 24666206
TI  - From molecular dehydration to excess volumes of phase-separating PNIPAM
      solutions.
AB  - For aqueous poly(N-isopropyl acrylamide) (PNIPAM) solutions, a structural
      instability leads to the collapse and aggregation of the macromolecules at the
      temperature-induced demixing transition. The accompanying cooperative dehydration
      of the PNIPAM chains is known to play a crucial role in this phase separation. We
      elucidate the impact of partial dehydration of PNIPAM on the volume changes
      related to the phase separation of dilute to concentrated PNIPAM solutions. Quasi
      elastic neutron scattering enables us to directly follow the isotropic jump
      diffusion behavior of the hydration water and the almost freely diffusing water.
      As the hydration number decreases from 8 to 2 for the demixing 25 mass % PNIPAM
      solution, only a partial dehydration of the PNIPAM chains occurs. Dilatation
      studies reveal that the transition-induced volume changes depend in a remarkable
      manner on the PNIPAM concentration of the solutions. The excess volume per mole
      of H2O molecules expelled from the solvation layers of PNIPAM during phase
      separation probably strongly increases from dilute to concentrated PNIPAM
      solutions. This finding is qualitatively related to the immense strain-softening
      previously observed for demixing PNIPAM solutions. 

PMID- 24666207
TI  - Anemia in malignancies: pathogenetic and diagnostic considerations.
AB  - OBJECTIVES: The aim of this paper is to review the pathogenesis and diagnostic
      approaches to anemia in cancer patients. METHODS: PubMed was queried for various
      combinations of anemia and cancer-related terms using appropriate filters for
      articles and practice guidelines published in the last 5 years. Specific searches
      were conducted for individual pathogenetic mechanisms and malignancies of
      specific anatomic sites. RESULTS: Anemia is the commonest hematological
      manifestation of cancer, afflicting 40-64% of patients treated for malignancies.
      Pathophysiologically, cancer-related anemia can be classified into four broad but
      overlapping categories: hypoproliferative anemia including the common anemia of
      inflammation/chronic disease, hemolytic anemia, miscellaneous etiologies, and
      uncertain etiologies. Anemia incidence increases with the administration of
      chemotherapy/radiotherapy. It reduces the quality of life and shortens survival
      in cancer patients. A positive correlation is observed between anemia and tumor
      hypoxia. Experimentally, hypoxemia enhances tumor growth and resistance to
      therapy by stimulating angiogenesis, acquisition of genomic mutations, and
      increasing resistance to apoptosis as well as to the killing effects of
      chemo/radiotherapy-generated free radicals. DISCUSSION: Diagnostic approaches to
      the anemic cancer patient begin with a detailed clinical history and physical
      examination. Peripheral blood morphology and reticulocyte count are also helpful.
      Patients with unexplained anemia are evaluated by standard approaches also used
      in patients of similar age without malignancy. Serum iron profile and bone marrow
      examination are often required in difficult cases. This review focuses on major
      aspects of the pathogenesis of the individual entities. Diagnostic approaches and
      uncommon causes including hemophagocytic lymphohistiocytosis, acquired
      hemoglobinopathies, and myelodysplasia are also discussed.

PMID- 24666208
TI  - Reversible near-infrared light directed reflection in a self-organized helical
      superstructure loaded with upconversion nanoparticles.
AB  - Adding external, dynamic control to self-organized superstructures with desired
      functionalities is an important leap necessary in leveraging the fascinating
      molecular systems for applications. Here, the new light-driven chiral molecular
      switch and upconversion nanoparticles, doped in a liquid crystal media, were able
      to self-organize into an optically tunable helical superstructure. The resulting
      nanoparticle impregnated helical superstructure was found to exhibit
      unprecedented reversible near-infrared (NIR) light-guided tunable behavior only
      by modulating the excitation power density of a continuous-wave NIR laser (980
      nm). Upon irradiation by the NIR laser at the high power density, the reflection
      wavelength of the photonic superstructure red-shifted, whereas its reverse
      process occurred upon irradiation by the same laser but with the lower power
      density. Furthermore, reversible dynamic NIR-light-driven red, green, and blue
      reflections in a single thin film, achieved only by varying the power density of
      the NIR light, were for the first time demonstrated. 

PMID- 24666209
TI  - Pulmonary function studies, still a priority in COPD.

PMID- 24666212
TI  - Analysis of asphaltic binders modified with PPA by surface techniques.
AB  - Samples of unmodified and modified asphalt binders containing 1% polyphosphoric
      acid were studied. Fourier-transform infrared spectroscopy was used to evaluate
      the structural indices of the functional groups present in the samples and the
      results indicated there was a strong interaction between the polyphosphoric acid
      and oxygenated species. Contact angle measurements indicated that adhesion of the
      binder to the aggregate depended on the polyphosphoric acid content. Atomic force
      microscopy was used to relate features observed on the surface of the asphalt
      binder 50/70, with their local mechanical properties such as stiffness and
      elasticity. It was observed that the surface of the sample containing 1%
      polyphosphoric acid provides stiffness values lower than the unmodified asphalt
      binder. 

PMID- 24666211
TI  - Extraocular sebaceous carcinoma in situ: report of three cases and review of the
      literature.
AB  - Extraocular sebaceous carcinoma is a rare neoplasm. Purely in situ extraocular
      sebaceous carcinoma is extremely rare and somewhat controversial. Review of the
      literature reveals only three reported cases, two of which involved the head and
      neck and one the arm. The ones on the head and neck arose in association with an
      actinic keratosis. We report three cases of extraocular sebaceous carcinoma in
      situ and describe the first report of immunoperoxidase screening for mismatch
      repair proteins in such tumors.

PMID- 24666210
TI  - Quality assurance of spirometry in a population-based study -predictors of good
      outcome in spirometry testing.
AB  - BACKGROUND: The assurance of high-quality spirometry testing remains a challenge.
      METHODS: Spirometry training consisted of standardized coaching followed by
      certification for 35 spirometry-naive and 9 spirometry-experienced research
      assistants. Spirometry was performed before and after bronchodilator (BD) in
      random population samples of 5176 people aged 40 years and older from 9 sites in
      Canada. using the hand-held EasyOne spirometer (ndd Medical Technologies Inc.,
      Andover, MA, USA). Pulmonary function quality assurance with over reading was
      conducted centrally in Vancouver: spirograms were reviewed and graded according
      to ATS/ERS standards with prompt feedback to the technician at each site.
      Descriptive statistics were calculated for manoeuvre acceptability and
      repeatability variables. A logistic regression model was constructed for the
      predictors of spirometry quality success. RESULTS: 95% of test sessions achieved
      pre-determined quality standards for back extrapolated volume (BEV), time to peak
      flow (PEFT) and end of test volume (EOTV). The mean forced expiratory time (FET)
      was 11.2 seconds. Then, 90% and 95% of all manoeuvres had FEV1 and FVC that were
      repeatable within 150 ml and 200 ml respectively. Test quality was slightly
      better for post-BD test sessions compared with pre-BD for both groups of research
      assistants. Independent predictors of acceptable test quality included
      participant characteristics: female sex, younger age, greater BD responsiveness;
      but not study site or prior experience in completing spirometry by the
      technologist. CONCLUSIONS: Good quality spirometry tests are attainable in large
      multicenter epidemiological studies by trained research assistants, irrespective
      of their prior experience in spirometry.

PMID- 24666204
TI  - Neuromyelitis optica: clinical features, immunopathogenesis and treatment.
AB  - The term 'neuromyelitis optica' ('Devic's syndrome', NMO) refers to a syndrome
      characterized by optic neuritis and myelitis. In recent years, the condition has
      raised enormous interest among scientists and clinical neurologists, fuelled by
      the detection of a specific serum immunoglobulin (Ig)G reactivity (NMO-IgG) in up
      to 80% of patients with NMO. These autoantibodies were later shown to target
      aquaporin-4 (AQP4), the most abundant water channel in the central nervous system
      (CNS). Here we give an up-to-date overview of the clinical and paraclinical
      features, immunopathogenesis and treatment of NMO. We discuss the widening
      clinical spectrum of AQP4-related autoimmunity, the role of magnetic resonance
      imaging (MRI) and new diagnostic means such as optical coherence tomography in
      the diagnosis of NMO, the role of NMO-IgG, T cells and granulocytes in the
      pathophysiology of NMO, and outline prospects for new and emerging therapies for
      this rare, but often devastating condition. 

PMID- 24666213
TI  - Differences in contraceptive use between Spanish female healthcare providers and
      Spanish women in the general population aged 23 to 49 years: the HABITS Study.
AB  - OBJECTIVE: To compare the contraceptive modalities used in the general female
      population with those of female healthcare providers (HCPs) in Spain. METHODS: A
      nationwide survey of a representative sample of Spanish women and female Spanish
      HCPs aged 23 to 49 years (total sample size: 3200). RESULTS: The condom was the
      most widely used contraceptive method in both groups (30% and 23% in the general
      population and among HCPs, respectively). The reasons cited for relying on this
      method were ease of use (19% and 13%, respectively; p = 0.2), effectiveness (16%
      and 22%, respectively; p = 0.2), absence of side effects (14% and 22%,
      respectively; p = 0.1), and fear of side effects associated with oral
      contraception (13% and 2%, respectively; p < 0.0001). After the condom, oral
      contraceptives, the intrauterine device and the vaginal ring were the most widely
      used methods among HCPs (13% each). CONCLUSIONS: The spectrum of contraceptive
      methods used by female HCPs differs from that of women in the general Spanish
      population. HCPs opt more often for long-acting reversible contraceptives because
      of their effectiveness and safety whereas women in the general population rely
      more frequently on the condom and surgical methods.

PMID- 24666214
TI  - Isotopic investigation of niche partitioning among native carnivores and the non
      native coyote (Canis latrans).
AB  - We employed stable carbon (delta(13)C) and nitrogen (delta(15)N) isotopes within
      a hypothetico-deductive framework to explore potential resource partitioning
      among terrestrial mammalian carnivores. Isotope values were acquired using guard
      hair samples from bobcat (Lynx rufus), coyote (Canis latrans), gray fox (Urocyon
      cinereoargenteus), and red fox (Vulpes vulpes) in the Adirondack Park, NY, USA.
      Enrichment along the delta(13)C axis was expected to reflect the use of human
      sources of food (reflecting a corn subsidy), and by extension tolerance for human
      modified environments, whereas enrichment along the delta(15)N axis was expected
      to reflect a higher level of carnivory (i.e. amount of animal-based protein in
      the diet) - two mechanisms by which these now sympatric species may achieve a
      dynamic coexistence. Although bobcats were the only obligate carnivore, all four
      species shared a similar delta(15)N space. In contrast, bobcat had a lower and
      distinct delta(13)C signature compared to foxes, consistent with the a priori
      expectation of bobcats being the species least tolerant of human activities.
      Isotope signatures for coyotes, which colonized the region in the 1920s,
      overlapped all three native carnivores, bobcats the least, gray fox the most,
      indicating their potential competitive influence on this suite of native
      carnivores. 

PMID- 24666215
TI  - Risk of mucocutaneous toxicities in patients with solid tumors treated with
      sorafenib: an updated systematic review and meta-analysis.
AB  - We performed a systematic review and meta-analysis of mucocutaneous toxicities
      associated with sorafenib, an oral multi tyrosine kinase inhibitor. Eligible
      studies included randomized Phase II and III trials of patients with solid tumors
      on sorafenib daily describing events of hand foot skin reaction, skin rash,
      alopecia, stomatitis or pruritis. Patients treated with sorafenib had a
      significantly increased risk of all-grade mucocutaneous toxicities. The RR of all
      grade hand foot skin reaction, skin rash, alopecia, stomatitis and pruritis were
      4.33 (95% CI: 3.06-6.14), 2.67 (95% CI: 1.86-3.83), 3.93 (95% CI: 2.07-7.45), 2.9
      (95% CI: 2.26-3.73), 2.29 (95% CI: 1.87-3.03); respectively. Exploratory subgroup
      analysis showed no effect of tumor types or treatment regimen (monotherapy versus
      combination) on the RR of mucocutaneous toxicities. Our meta-analysis has
      demonstrated that sorafenib is associated with a higher risk of developing all
      grade mucocutaneous toxicities compared with control.

PMID- 24666216
TI  - Cervical referral of head pain in migraineurs: effects on the nociceptive blink
      reflex.
AB  - OBJECTIVE: To investigate cervical, interictal reproduction of usual head pain
      and its effect on the nociceptive blink reflex in migraineurs. BACKGROUND:
      Anatomical and neurophysiological studies in animals and humans have confirmed
      functional convergence of trigeminal and cervical afferent pathways. Migraineurs
      often present with occipital and neck symptoms, and cervical pain is referred to
      the head in most cases, suggesting that cervical afferent information may
      contribute to headache. Furthermore, the effectiveness of greater occipital nerve
      blockade in migraine and demonstrable modulation of trigeminal transmission
      following greater occipital nerve blockade suggest an important role for cervical
      afferents in migraine. However, to what extent cervical afferents contribute
      actively to migraine is still unknown. METHODS: The passive accessory
      intervertebral movements of the atlanto-occipital and C2-3 spinal segments of 15
      participants (14 females, 1 male; age 24-44 years, mean age 33.3 years) with
      migraine were examined interictally. During 1 session, either the atlanto
      occipital or C2-3 segment was examined, resulting in referred usual head pain,
      while in another session, pressure was applied over the common extensor origin
      (lateral epicondyle of the humerus) of the ipsilateral arm. Each intervention was
      repeated 4 times. The nociceptive blink reflex to a supraorbital electrical
      stimulus was elicited ipsilaterally during both sessions before and during each
      intervention. The main outcome variables were the number of recorded blinks, area
      under the curve and latencies of the R2 components of the nociceptive blink
      reflex. Participants also rated the intensity of referred head pain and the
      supraorbital stimulus on a scale of 0-10, where 0 = "no pain" and 10 =
      "intolerable pain," and rated the intensity of applied pressure where 0 =
      "pressure but no pain" and 10 = "intolerable pain." RESULTS: Participants
      reported a significant reduction in local tenderness ratings across the 4 trials
      for the cervical intervention but not for the arm (P = .005). The cervical
      intervention evoked head pain in all participants. As the cervical intervention
      was sustained, head pain decreased significantly from the beginning to the end of
      each trial (P = .000) and from the beginning of the first trial to the end of the
      last (P = .000). Pain evoked by the supraorbital stimulus was consistent from
      baseline to across the 4 trials (P = .635) and was similar for the cervical and
      arm interventions (P = .072). The number of blinks decreased significantly across
      the experiment (P = .000) and was comparable in the cervical and arm
      interventions (P = .624). While the R2 area under the curve decreased
      irrespective of intervention (P = .000), this reduction was significantly greater
      for the cervical intervention than when pressure was applied to the arm (P =
      .037). Analysis of the R2 latencies revealed a notable increase across the
      experiment (P = .037). However, this increase was significantly greater following
      the cervical than arm intervention (P = .012). CONCLUSIONS: Our findings
      corroborate previous results related to anatomical and functional convergence of
      trigeminal and cervical afferent pathways in animals and humans, and suggest that
      manual cervical modulation of this pathway is of potential benefit in migraine.

PMID- 24666217
TI  - Ivorenolide B, an immunosuppressive 17-membered macrolide from Khaya ivorensis:
      structural determination and total synthesis.
AB  - Ivorenolide B (1), an unprecedented 17-membered macrolide featuring conjugated
      acetylenic bonds and four chiral centers, was isolated from Khaya ivorensis. The
      structure of 1 was fully determined by spectroscopic analysis and total syntheses
      of its four most possible stereoisomers. Compound 1 showed significant
      immunosuppressive activity. 

PMID- 24666218
TI  - Effective treatment of scrotal lichen simplex chronicus with 0.1% tacrolimus
      ointment: an observational study.

PMID- 24666219
TI  - Harmlessness and narration.

PMID- 24666220
TI  - Occupational therapy and culture: a literature review.
AB  - BACKGROUND: Occupational therapy has culture as a relevant phenomenon of
      interest. Culture appears increasingly often in occupational therapy research,
      from diverse approaches and foci. As culture is difficult to define, and has
      political and ethical implications, an investigation into its usage is warranted.
      AIM: To identify and describe how culture as a broad phenomenon is expressed in
      OT research published between 2006 and 2011, regarding knowledge development in
      the discipline and its impact on practice. METHODS: A qualitative study was
      carried out, using an integrative literature review. Thirty-nine studies in
      English were included. RESULTS: From the analysis, two dimensions concerning
      expressions of culture emerged: "culture is alive" and "occupational therapy as a
      culture". Aside from these dimensions, a group of forces that have an impact on
      these dimensions is described. CONCLUSIONS: In its understanding of expressions
      of culture, occupational therapy stands at a crossroads between traditional and
      critical approaches. A lack of critical insight into professional knowledge
      increases the risk that occupational therapy will remain satisfied with the
      current understanding of culture, based on the dominant knowledge. The discipline
      could fail to address the political, ethical, and theoretical issues required to
      reach the targeted diversity in its practice.

PMID- 24666222
TI  - The differential diagnosis of splachnic vein thrombosis.

PMID- 24666221
TI  - 'Just a little hint': bisexual-specific microaggressions and their connection to
      epistemic injustices.
AB  - A growing body of evidence indicates disproportionate rates of mental health
      disorders among bisexual women compared to both heterosexual and lesbian women.
      Such disparities are often attributed to stressors related to minority status,
      including experiences of prejudice and discrimination. Prior research has made
      little distinction between the prejudicial experiences of bisexual groups as
      compared to lesbian/gay groups. Based on qualitative data gathered in focus
      groups with 10, predominantly White, bisexual-identified women, which occurred in
      a large city in the USA, we posit that differences in prejudicial experiences do
      exist for bisexual groups, and that such differences reside in the realms of the
      epistemic, yet have very real implications for bisexual women's daily lived
      experiences. We discuss everyday slights and insults, also known as
      microaggressions, reported by the participants vis-a-vis their bisexual identity.
      These bisexual-specific microaggressions include hostility; denial/dismissal;
      unintelligibility; pressure to change; lesbian, gay, bisexual and transgender
      legitimacy; dating exclusion; and hypersexuality. We consider how such
      microaggressions may adversely impact mental health and well-being and may assist
      in explaining the mental health disparities among bisexual women. 

PMID- 24666223
TI  - Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria.
AB  - Combination antibiotic therapy for Gram-negative sepsis is controversial. The
      present review provides a brief summary of the existing knowledge on combination
      therapy for severe infections with multidrug-resistant Pseudomonas spp.,
      Acinetobacter spp., and Enterobacteriaceae. Empirical combination antibiotic
      therapy is recommended for severe sepsis and septic shock to reduce mortality
      related to inappropriate antibiotic treatment. Because definitive combination
      therapy has not been proven superior to monotherapy in meta-analyses, it is
      generally advised to de-escalate antibiotic therapy when the antibiotic
      susceptibility profile is known, although it cannot be excluded that some
      subgroups of patients might still benefit from continued combination therapy.
      Definitive combination therapy is recommended for carbapenemase-producing
      Enterobacteriaceae and should also be considered for severe infections with
      Pseudomonas and Acinetobacter spp. when beta-lactams cannot be used. Because
      resistance to broad-spectrum beta-lactams is increasing in Gram-negative bacteria
      and because no new antibiotics are expected to become available in the near
      future, the antibacterial potential of combination therapy should be further
      explored. In vitro data suggest that combinations can be effective even if the
      bacteria are resistant to the individual antibiotics, although existing evidence
      is insufficient to support the choice of combinations and explain the synergistic
      effects observed. In vitro models can be used to screen for effective
      combinations that can later be validated in animal or clinical studies. Further,
      in the absence of clinical evidence, in vitro data might be useful in supporting
      therapeutic decisions for severe infections with multidrug-resistant Gram
      negative bacteria.

PMID- 24666224
TI  - Syntheses of new tuberculosis inhibitors promoted by microwave irradiation.
AB  - Tuberculosis (TB) represents a major public health problem. The growing number of
      (extensively) multi-drug resistance cases indicates that there is an urgent need
      for discovery of new anti-TB entities, addressed towards new and specific
      targets, and continuous development of fast and efficient synthetic strategies to
      access them easily. Microwave-assisted chemistry is well suited for small-scale
      laboratory synthetic work, allowing full control of reaction conditions, such as
      temperature, pressure, and time. Microwave-assisted high-speed organic synthesis
      is especially useful in the lead optimization phase of drug discovery. To
      illustrate the advantages of modern microwave heating technology, we herein
      describe applications and approaches that have been useful for the synthesis of
      new drug-like anti-TB compounds.

PMID- 24666225
TI  - Roles of retinoic acid signaling in normal and abnormal development of the palate
      and tongue.
AB  - Palatogenesis involves various developmental events such as growth, elevation,
      elongation and fusion of opposing palatal shelves. Extrinsic factors such as
      mouth opening and subsequent tongue withdrawal are also needed for the horizontal
      elevation of palate shelves. Failure of any of these steps can lead to cleft
      palate, one of the most common birth defects in humans. It has been shown that
      retinoic acid (RA) plays important roles during palate development, but excess RA
      causes cleft palate in fetuses of both rodents and humans. Thus, the coordinated
      regulation of retinoid metabolism is essential for normal palatogenesis. The
      endogenous RA level is determined by the balance of RA-synthesizing
      (retinaldehyde dehydrogenases: RALDHs) and RA-degrading enzymes (CYP26s). Cyp26b1
      is a key player in normal palatogenesis. In this review, we discuss recent
      progress in the study of the pathogenesis of RA-induced cleft palate, with
      special reference to the regulation of endogenous RA levels by RA-degrading
      enzymes. 

PMID- 24666227
TI  - Automated dispersive liquid-liquid microextraction-gas chromatography-mass
      spectrometry.
AB  - An innovative automated procedure, low-density solvent based/solvent
      demulsification dispersive liquid-liquid microextraction (automated DLLME)
      coupled to gas chromatography-mass spectrometry (GC/MS) analysis, has been
      developed. The most significant innovation of the method is the automation. The
      entire procedure, including the extraction of the model analytes (phthalate
      esters) by DLLME from the aqueous sample solution, breaking up of the emulsion
      after extraction, collection of the extract, and analysis of the extract by
      GC/MS, was completely automated. The applications of low-density solvent as
      extraction solvent and the solvent demulsification technique to break up the
      emulsion simplified the procedure and facilitated its automation. Orthogonal
      array design (OAD) as an efficient optimization strategy was employed to optimize
      the extraction parameters, with all the experiments conducted auotmatically. An
      OA16 (4(1) * 2(12)) matrix was initially employed for the identification of
      optimized extraction parameters (type and volume of extraction solvent, type and
      volume of dispersive solvent and demulsification solvent, demulsification time,
      and injection speed). Then, on the basis of the results, more levels (values) of
      five extraction parameters were investigated by an OA16 (4(5)) matrix and
      quantitatively assessed by the analysis of variance (ANOVA). Enrichment factors
      of between 178- and 272-fold were obtained for the phthalate esters. The
      linearities were in the range of 0.1 and 50 MUg/L and 0.2 and 50 MUg/L, depending
      on the analytes. Good limits of detection (in the range of 0.01 to 0.02 MUg/L)
      and satisfactory repeatability (relative standard deviations of below 5.9%) were
      obtained. The proposed method demonstrates for the first time integrated sample
      preparation by DLLME and analysis by GC/MS that can be operated automatically
      across multiple experiments. 

PMID- 24666226
TI  - HIV-related stigma and symptoms of post-traumatic stress disorder and depression
      in HIV-infected individuals: does social support play a mediating or moderating
      role?
AB  - HIV stigma plays a major role in the etiology of psychological distress among
      persons living with HIV, but may be ameliorated by social support. This cross
      sectional study examined whether social support mediates or moderates the
      relationship between HIV stigma and psychological symptoms. We recruited a
      convenience sample of 210 individuals living with HIV in three peri-urban
      communities in the Western Cape, South Africa. People living with HIV and AIDS
      (PLWHA) completed self-report questionnaires that assessed HIV-related stigma,
      social support, post-traumatic stress disorder (PTSD) and depression. Product
      term regression analyses showed that social support played a mediating role in
      the relationship between HIV-related stigma and symptoms of PTSD (not
      depression). Social support did not, however, moderate the relationship between
      HIV-related stigma and PTSD or depression. The results indicate that perceived
      HIV-related stigma may decrease PLWHA's perceived level of social support, which
      in turn may increase PTSD symptoms. Moreover, these findings suggest that despite
      the protective role of social support, there are other factors that affect the
      relationship between HIV-related stigma and mental health that hinder the
      buffering role of social support in this relationship. These findings may have
      implications for designing and implementing interventions that increase perceived
      social support and decrease perceived HIV-related stigma, which in turn may
      decrease symptoms of PTSD among PLWHA.

PMID- 24666228
TI  - A first-principles model of Fermi resonance in the alkyl CH stretch region:
      application to hydronaphthalenes, indanes, and cyclohexane.
AB  - The infrared (IR) spectroscopy of the alkyl CH stretch region (2750-3000 cm(-1))
      of a series of bicyclic hydrocarbons and free radicals has been studied under
      supersonic expansion cooling in the gas phase, and compared with a theoretical
      model that describes the local mode stretch-bend Fermi resonance interactions.
      The double resonance method of fluorescence-dip infrared (FDIR) spectroscopy was
      used on the stable molecules 1,2-dihydronaphthalene, 1,4-dihydronaphthalene,
      tetralin, indene, and indane using the S0-S1 origin transition as a monitor of
      transitions. Resonant ion-dip infrared (RIDIR) spectra were recorded for the
      trihydronaphthyl (THN) and inden-2-yl methyl (I2M) radicals. The previously
      developed model Hamiltonian (J. Chem. Phys. 2013, 138, 064308) incorporates cubic
      stretch-bend coupling with parameters obtained from density functional theory
      methods. Full dimensional calculations are compared to reduced dimensional
      Hamiltonian results in which anharmonic CH stretches and CH2 scissor modes are
      Fermi coupled. Excellent agreement between theoretical results is found. Scale
      factors of select terms in the reduced dimensional Hamiltonian, obtained by
      fitting the theoretical Hamiltonian predictions to the experimental spectra, are
      found to be similar to previous work. The resulting Hamiltonian predicts
      successfully all the major spectral features considered in this study. A
      simplified model is introduced in which the CH2 groups are decoupled. This model
      enables the assignment of many of the spectral features. The model results are
      extended to describe the CH stretch spectrum of the chair and twist-boat
      conformers of cyclohexane. The chair conformer is used to illustrate the
      shortcomings of the CH2 decoupling model. 

PMID- 24666229
TI  - Serum cytokine and chemokine profiles in patients with myasthenia gravis.
AB  - Myasthenia gravis (MG) is an autoimmune-mediated inflammatory disease of the
      neuromuscular junction. Previous studies of animal MG models have suggested
      important roles of cytokines in MG pathogenesis, but adequate studies on
      cytokines in human MG are lacking. Using a multiplex suspension array system, we
      measured the serum levels of 27 cytokines/chemokines in 47 anti-acetylcholine
      receptor antibody-positive patients with MG and 20 normal controls (NC) to
      investigate the contribution of cytokines/chemokines toward MG pathogenesis.
      Correlations between clinical parameters and cytokine/chemokine levels in
      patients with MG were also examined. The serum levels of interleukin (IL)-15
      (mean +/- standard deviation: 6.85 +/- 6.97 pg/ml) and vascular endothelial
      growth factor (VEGF) (96.21 +/- 71.60 pg/ml) significantly increased, whereas IL
      4 levels (3.57 +/- 0.86 pg/ml) decreased in patients with MG compared with NC (IL
      15: 4.42 +/- 1.55 pg/ml; VEGF: 63.51 +/- 32.95 pg/ml; IL-4: 4.15 +/- 0.81 pg/ml,
      P < 0.05). In addition, eight cytokines (IL-4, IL-8, IL-15, eotaxin, macrophage
      inflammatory protein-1alpha, macrophage inflammatory protein-1beta, VEGF and IL
      1b) were significantly changed among MG patients with thymoma, MG patients
      without thymoma and NC (P < 0.05). Some cytokines, such as IL-4, IL-15, and VEGF,
      may play roles in the pathogenesis of MG. 

PMID- 24666230
TI  - Chlorin e6 derivative radachlorin mainly accumulates in mitochondria, lysosome
      and endoplasmic reticulum and shows high affinity toward tumors in nude mice in
      photodynamic therapy.
AB  - The efficacy of photodynamic therapy (PDT) depends upon the amount of
      photosensitizer accumulated in the malignant tissues. Radachlorin is a popular
      photosensitizer used in photodynamic therapy to treat various types of cancer. In
      this study, we have studied the main organelles responsible for the accumulation
      of radachlorin in human anaplastic thyroid cancer in vitro and in vivo. The
      optimal time window for uptake and clearance of radachlorin also was studied.
      Confocal microscopic images confirmed that the radachlorin is mainly acquired by
      mitochondria and partially by lysosome and endoplasmic reticulum. Studies also
      showed that the maximum amount of radachlorin was accumulated within 3-6 h after
      the treatment. Radachlorin also showed a higher affinity toward malignant tumors
      compared to the other organs in mice xenograft model. Uptake of radachlorin
      reached an optimum amount within 6 h and most of the radachlorins were also
      cleared from the body in next 48 h. Therefore, detailed information regarding
      exact accumulation sites and a time window in which maximum amount of drug is
      accumulated and cleared were obtained by this study. Hence, not only the efficacy
      of the treatment can be increased but the phototoxicity after the treatment also
      can be controlled. 

PMID- 24666232
TI  - Judicious design of indoline chromophores for high-efficiency iodine-free dye
      sensitized solar cells.
AB  - Indoline photosensitizers exhibit impressive short-circuit photocurrent but
      generally low molar extinction coefficient and rapid charge recombination, which
      limits their application in thin-film dye-sensitizerd solar cells (DSCs). Here,
      we incorporate a new dithieno[3,2-b:2',3'-d]pyrrole (DTP) segment (i.e.,
      dihexyloxy-triphenylamine (DHO-TPA) substituted DTP) as the conjugated pi-linker
      to construct a series of high molar absorption coefficient indoline dyes (XW69,
      XW70, and XW71) for DSCs employing a cobalt(II/III) redox electrolyte.
      Interestingly, this DTP linker is demonstrated as an efficient building block,
      not only slowing down the kinetics of charge recombination of titania electrons
      with tris(1,10-phenanthroline)cobalt(III) ions but also making a great
      contribution to the light absorption properties in comparison with the
      dihexylaniline substituted DTP. With respect to the dihexyloxy-triphenylamine dye
      (XW68), these new indoline dyes exhibit stronger light-harvesting and thus better
      power conversion efficiency of DSCs made from thin titania films. Benefitting
      from the bulky rigidity of the donor and pi-conjugation unit, the XW70 dye
      displays a promising conversion efficiency as high as 8.78%, with a short-circuit
      current density (J(SC)) of 13.3 mA cm(-2), open-circuit voltage (V(OC)) of 943
      mV, and fill factor (FF) of 0.70 under AM 1.5 illumination (100 mW cm(-2)).
      Furthermore, the effect of light irradiation on these dyes adsorbed on
      nanocrystalline TiO2 films was investigated, proving the photostability of these
      indoline chromophores. Our work has valued the feasibility of judicious design of
      indoline chromophores to obtain organic photosensitizers for high-efficiency
      iodine-free DSCs made from thin titania films.

PMID- 24666231
TI  - Atypical fibrous histiocytoma of the skin with CD30 and p80/ALK1 positivity and
      ALK gene rearrangement.
AB  - We report the case of a two patients who presented with a solitary, asymptomatic,
      angiomatoid nodule on the right thigh. Histopathological finding showed a poorly
      circumscribed lesion, located in the dermis. The morphological aspect strongly
      suggested the diagnosis of atypical fibrous histiocytoma (AFH), but surprisingly,
      the neoplastic cells were diffusely CD30+, with a membrane staining devoid of
      paranuclear dot. The lesions were tested for p80/ALK1 expression. Surprisingly,
      we found a diffuse cytoplasmic positivity. Interestingly, using break-apart
      fluorescent in situ hybridization (FISH), we evidenced an ALK rearrangement in
      nearly 50% of the neoplastic cells. The expression of CD30 and ALK1 with ALK gene
      rearrangement raised the possibility of three diagnoses: a primary cutaneous
      anaplastic large cell lymphoma (ALCL), a cutaneous inflammatory myofibroblastic
      tumor (IMT), an AFH of the skin associated with ALK gene rearrangement and CD30
      positivity. The three hypotheses were discussed and finally, although p80/ALK1
      expression and cytogenetic abnormalities in fibrous histiocytoma (FH) are not yet
      reported to the best of our knowledge, we favored the diagnosis of AFH. 

PMID- 24666233
TI  - The importance of quality over in quantity in the social sharing of emotions
      (SSE) in people living with HIV/AIDS.
AB  - Research shows that chronic illness patients encounter difficulties in the social
      sharing of emotions (SSE). Since most SSE studies focus on quantitative aspects,
      the present study, aimed, among others, to study the associations between the
      quality of SSE in people living with HIV/AIDS and patients' psychological and
      physical well-being. A total of 101 HIV/AIDS patients answered a questionnaire
      (Likert scale items) which assessed: shame, guilt, perceived stigma, reasons for
      non-disclosure of serostatus, physical health, mental health, SSE and quality of
      SSE. While no associations were found between quantitative aspects of SSE,
      physical health and mental health, the quality of SSE was negatively correlated
      to shame and guilt, and positively correlated to physical and mental health.
      Furthermore, mediation analyses showed the mediating role of the quality of SSE
      in the relationship between, on the one hand, shame and guilt; and on the other
      hand, physical and mental health. Findings suggest the importance of qualitative
      aspects of SSE in the emergence of positive outcomes linked to emotional
      expression in people living with HIV/AIDS.

PMID- 24666235
TI  - X-ray structures of human furin in complex with competitive inhibitors.
AB  - Furin inhibitors are promising therapeutics for the treatment of cancer and
      numerous infections caused by bacteria and viruses, including the highly lethal
      Bacillus anthracis or the pandemic influenza virus. Development and improvement
      of inhibitors for pharmacological use require a detailed knowledge of the
      protease's substrate and inhibitor binding properties. Here we present a novel
      preparation of human furin and the first crystal structures of this enzyme in
      complex with noncovalent inhibitors. We show the inhibitor exchange by soaking,
      allowing the investigation of additional inhibitors and substrate analogues.
      Thus, our work provides a basis for the rational design of furin inhibitors. 

PMID- 24666237
TI  - Klippel-Trenaunay-Weber syndrome (KTWS) and spontaneous spinal CSF leak:
      coincidence or link.
AB  - OBJECTIVE: To highlight the occurrence of spontaneous cerebrospinal fluid (CSF)
      leak in the setting of Klippel-Trenaunay-Weber syndrome (KTWS). BACKGROUND: KTWS
      is a congenital multicomponent disorder of angiogenesis plus limb asymmetry. The
      cause of spontaneous CSF leaks often remains unknown, but the notion of a pre
      existing dural weakness related to a disorder of connective tissue matrix is
      gaining momentum. REPORT OF CASES AND METHODS: Two women with KTWS developed
      spontaneous CSF leaks. Each underwent extensive head and spine imaging studies.
      One patient underwent surgery to treat the CSF leak and later an epidural blood
      patch upon partial recurrence of her symptoms. The other patient, who had
      intermittent CSF leak, developed cerebral venous thrombosis requiring several
      months of anticoagulation therapy. Both patients have histories of visceral
      bleeding: gastrointestinal in 1 patient and genitourinary in the other. RESULTS:
      The predominant site of vascular anomaly was the left lower limb in 1 patient and
      the right upper limb in the other, while the involved limb was larger in 1
      patient and smaller in the other. Each patient presented with orthostatic
      headaches. One had additional choreiform movements and cognitive difficulties
      that responded to the treatment of the leak. Head magnetic resonance imaging in
      both patients showed diffuse pachy meningeal enhancement and evidence of sinking
      of the brain. Computed tomography myelography in 1 patient disclosed the site of
      the leak; and she underwent surgery to treat the leak, and later an epidural
      blood patch upon partial recurrence of her symptoms to which she responded well.
      The other patient had intermittent leak with history of long remission and was
      reluctant to go through invasive diagnostic or therapeutic measures. CONCLUSION:
      The occurrence of an uncommon disorder (spontaneous CSF leak) in the setting of a
      rare congenital disorder in 2 unrelated patients is intriguing. Whether this
      represents coincidence or a link is not clear but deserves further observations
      and investigation.

PMID- 24666234
TI  - Diet, Helicobacter pylori strain-specific infection, and gastric cancer risk
      among Chinese men.
AB  - Evidence for the association of diet and gastric cancer is equivocal, and the
      majority of previous studies have not evaluated the interaction of diet and
      infection with Helicobacter pylori, the leading risk factor for gastric cancer.
      We examined these associations among 226 cases and 451 controls nested within a
      prospective cohort. Dietary intakes were calculated from validated food frequency
      questionnaires. Blood levels of 15 antibodies to Helicobacter pylori proteins
      were assessed using multiplex serology. Odds ratios (ORs) were calculated using
      logistic regression. Among individuals infected with high-risk Helicobacter
      pylori (sero-positivity to 5-6 virulent H. pylori proteins), increasing intake of
      red meat, heme iron, and sodium increased risk (comparing highest tertile to
      lowest: ORs [95% confidence interval {CI}]: 1.85 [1.01-3.40]; 1.95 [1.06-3.57];
      and 1.76 [0.91-3.43], respectively) while increasing intake of fruit decreased
      gastric cancer risk (comparing highest tertile of intake to lowest: OR [95% CI]:
      0.52 [0.28-0.94]). No associations of diet with risk were found among individuals
      infected with low-risk H. pylori (P for interaction for red meat and sodium: 0.02
      and 0.01, respectively). In this population with over 90% prevalence of CagA
      positive H. pylori infection, categorizing individuals using H. pylori multiplex
      serology may identify individuals for whom a diet intervention may be effective. 

PMID- 24666236
TI  - Two new phenolic compounds from Ficus rumphii and their antiproliferative
      activity.
AB  - Two new compounds 2 and 4, along with two known compounds 1 and 3, were isolated
      for the first time from 95% ethanolic extract of the leaves of Ficus rumphii.
      Their structures were elucidated on the basis of chemical and physical evidences
      (elemental analysis, UV, IR, (1)H NMR, (13)C NMR and mass spectra) and comparison
      with the literature compounds. Structural authentication of compound 4 was
      further validated by single-crystal X-ray analysis and DFT calculations. The
      compounds 1-4 were screened for in vitro cytotoxicity against cancer and non
      cancer cells and also tested for genotoxicity (comet assay). Compounds 2 and 4
      displayed significant activity against HL-60 with IC50 values of 3.3 and 2.3 MUM,
      respectively. The results revealed that compound 4 has better prospectus to act
      as cancer chemotherapeutic candidate which warrants further in vivo anticancer
      investigations. 

PMID- 24666238
TI  - A novel simultaneous photoelastic and two-beam interferometric system: I. Dynamic
      full-field evaluation of the elasticity modulus profile of polymeric fibres.
AB  - A novel optical setup for simultaneous capturing of photoelastic and two-beam
      interference patterns was designed. The designed optical setup was used to
      simultaneously record two types of patterns. The first pattern is two-beam
      interference pattern, and the second one is photoelastic interference pattern
      produced by objects under stress. This simultaneous capturing of the two patterns
      allowed us to calculate the full-field distribution of the elasticity modulus
      profile of fibres. A mathematical expression of the profile of the elasticity
      modulus was derived. This was applied to evaluate the elasticity modulus of
      anisotropic isotactic polypropylene fibres during stretching processes. The
      profile of the elasticity modulus was determined for both static and dynamic in
      situ cases where the propagation of different structural deformations was
      observed and studied using the designed optical setup. Patterns were given for
      illustration.

PMID- 24666239
TI  - Suboptimal antiretroviral therapy adherence among HIV-infected adults in
      Guangzhou, China.
AB  - Despite China's free antiretroviral therapy (ART) program, there are high rates
      of treatment failure, large sociodemographic disparities in care outcomes and
      emerging medication resistance. Understanding patient medication adherence
      behaviors and challenges could inform adherence interventions to maximize the
      individual and prevention benefits of ART. This study assessed recent
      nonadherence and treatment interruption among 813 HIV-infected adult outpatients
      in Guangzhou, China. Participants completed a behavioral survey, underwent chart
      review, and were tested for syphilis, gonorrhea, and chlamydia. Factors
      associated with suboptimal adherence were identified using univariate and
      multivariate logistic regression. Among 721 HIV-infected adults receiving ART,
      18.9% reported recent nonadherence (any missed ART in the past four weeks) and
      6.8% reported treatment interruption (four or more weeks of missed ART in the
      past year). Lower education, living alone, alcohol use, and being on ART one to
      three years were associated with recent nonadherence. Male gender, lower
      education, and being on ART one to three years were associated with treatment
      interruption. ART medication adherence interventions are needed in China that
      include individualized, long-term adherence plans sensitive to patients'
      educational and economic situations. These interventions should also consider
      possible gender disparities in treatment outcomes and address the use of alcohol
      during ART. Successful ART medication adherence interventions in China can inform
      other international settings that face similar adherence challenges and
      disparities.

PMID- 24666240
TI  - The multidisciplinary management of giant cell tumor of bone.
AB  - Giant cell tumor of bone is a locally aggressive lesion with a predilection for
      local recurrence, and in a small proportion of patients, metastatic disease can
      develop. Surgery is the mainstay of management for extremity-based lesions. For
      tumors located in challenging anatomical locations such as the sacrum and spine
      however, surgery may be associated with unacceptable functional morbidity. There
      are limited data regarding other treatment modalities such as radiation therapy,
      cytotoxic chemotherapy, interferon and bisphosphonates. Serial arterial
      embolization can be effective in some cases. Recent evidence has demonstrated
      denosumab to be a promising agent in the treatment of unresectable or metastatic
      disease. 

PMID- 24666241
TI  - Iron-catalyzed hetero-cross-dehydrogenative coupling reactions of sulfoximines
      with diarylmethanes: a new route to N-alkylated sulfoximines.
AB  - An efficient iron-catalyzed C-N bond formation by hetero-cross-dehydrogenative
      coupling (CDC) between sulfoximines and diarylmethanes is described. The reaction
      shows good functional group tolerance and provides N-alkylated sulfoximines in
      moderate to good yields. 

PMID- 24666242
TI  - Stepping back.

PMID- 24666244
TI  - Does caries risk assessment predict the incidence of caries for special needs
      patients requiring general anesthesia?
AB  - OBJECTIVES: The aim of this study was to correlate the caries-related variables
      of special needs patients to the incidence of new caries. MATERIALS AND METHODS:
      Data for socio-demographic information and dental and general health status were
      obtained from 110 patients treated under general anesthesia because of their
      insufficient co-operation. The Cariogram program was used for risk assessment and
      other caries-related variables were also analyzed. Within a defined follow-up
      period (16.3 +/- 9.5 months), 64 patients received dental examinations to assess
      newly developed caries. RESULTS: At baseline, the mean (SD) values of the DMFT
      (decayed, missing and filled teeth) and DT (decayed teeth) for the total patients
      were 9.2 (6.5) and 5.8 (5.3), respectively. During the follow-up period, new
      caries occurred in 48.4% of the patients and the mean value (SD) of the increased
      DMFT (iDMFT) was 2.1 (4.2). The patients with a higher increment of caries (iDMFT
      >=3) showed significantly different caries risk profiles compared to the other
      patients (iDMFT <2) (p < 0.05). Close correlations existed between the caries
      increment and several caries-related variables; baseline DMFT, insufficient self
      tooth-brushing and malocclusion were greatly associated with new caries
      development. CONCLUSIONS: Caries risk assessment could predict the incidence of
      future caries in hospital-based dentistry. Past caries experience and inadequate
      oral hygiene maintenance were largely related to caries development in special
      needs patients.

PMID- 24666243
TI  - Is there a trend of decreasing prevalence of TMD-related symptoms with ageing
      among the elderly?
AB  - OBJECTIVE: Older adults have not been studied as much as younger ones regarding
      prevalence of TMD-related symptoms. The aim was to assess the prevalence of TMD
      related symptoms in two population samples, 70 and 80 years old. MATERIALS AND
      METHODS: Identical questionnaires were in 2012 sent to all subjects born in 1932
      and 1942 living in two Swedish counties. The response rate was 70.1%, resulting
      in samples of 5697 70- and 2922 80-year-old subjects. The questionnaire comprised
      53 questions. Answers to questions on problems regarding TMD-related symptoms and
      awareness of bruxism were analysed. RESULTS: Twelve per cent of the women and 7%
      of the men in the 70-year-old group reported some, rather great or severe
      problems regarding TMD pain. In the 80-year-olds the prevalence was 8% and 7%,
      respectively. Subjects who had problems with TMJ sounds reported difficulty to
      open the jaw wide 6-times and TMJ pain 10-13-times more frequently than subjects
      without such problems. Changes of taste and awareness of bruxism were the only
      variables significantly associated with TMD symptoms in both age groups. Number
      of teeth was not significantly associated with any of the TMD-related symptoms.
      CONCLUSIONS: Most of the elderly subjects had no severe problems with TMD-related
      symptoms, but 12% of the 70-year-old women reported some, rather great or severe
      problems. The marked gender difference at age 70 had disappeared in the 80-year
      old group. The prevalence was lower among the 80- compared with the 70-year-old
      subjects of both sexes. The results support the comorbidity between TMD-related
      symptoms and general health problems.

PMID- 24666245
TI  - Response to Letter to the editor: 'European guidelines for topical PDT part 1.
      JEADV 2013;27:536-544' DOI: 10.1111/jdv.12258.

PMID- 24666246
TI  - Co-existence of clonal expanded autologous and transplacental-acquired maternal T
      cells in recombination activating gene-deficient severe combined
      immunodeficiency.
AB  - It is commonly accepted that the presence of high amounts of maternal T cells
      excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We
      report a SCID patient with a novel mutation in the recombination activating gene
      (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS.
      Several assays, including representatives of specific T cell receptors (TCR),
      Vbeta families and TCR-gamma rearrangements, were performed in order to
      understand more clearly the nature and origin of the patient's T cells. The
      patient had oligoclonal T cells which, based on the patient-mother human
      leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal
      origin. These cell populations were different in their numbers of regulatory T
      cells (T(reg)) and the diversity of TCR repertoires. This is the first
      description of the co-existence of large amounts of clonal expanded autologous
      and transplacental-acquired maternal T cells in RAG1-deficient SCID.

PMID- 24666247
TI  - Hydrophilic interaction chromatography using a meter-scale monolithic silica
      capillary column for proteomics LC-MS.
AB  - A meter-scale monolithic silica capillary column modified with urea-functional
      groups for hydrophilic interaction liquid chromatography (HILIC) was developed
      for highly efficient separation of biological compounds. We prepared a
      ureidopropylsilylated monolithic silica capillary column with a minimum plate
      height of 12 MUm for nucleosides and a permeability of 2.1 * 10(-13) m(2), which
      is comparable with the parameters of monolithic silica-C18 capillary columns.
      Over 300,000 theoretical plates were experimentally obtained in HILIC with a 4 m
      long column at 8 MPa; this is the best result yet reported for HILIC. A 2 m long
      ureidopropylsilylated monolithic silica capillary column was utilized to develop
      a HILIC mode LC-MS system for proteomics applications. Using tryptic peptides
      from human HeLa cell lysate proteins, we identified the comparable numbers of
      peptides and proteins in HILIC with those in reversed-phase liquid chromatography
      (RPLC) using a C18-modified monolithic silica column when shallow gradients were
      applied. In addition, approximately 5-fold increase in the peak response on
      average was observed in HILIC for commonly identified tryptic peptides due to the
      high acetonitrile concentration in the HILIC mobile phase. Since HILIC mode LC-MS
      shows orthogonal selectivity to RPLC mode LC-MS, it is useful as a complementary
      tool to increase proteome coverage in proteomics studies. 

PMID- 24666248
TI  - Virtual reality exposure in anxiety disorders: impact on psychophysiological
      reactivity.
AB  - OBJECTIVES: Anxiety disorders are among the most frequently encountered
      psychiatric disorders. Recommended treatments include cognitive behavioural
      therapy (CBT) and/or medication. In recent years, beneficial effects of virtual
      reality (VR) exposure therapy have been shown, making this technique a promising
      addition to CBT. However, the ability of VR to mimic threatening stimuli in a way
      comparable to in vivo cues has been discussed. In particular, it has been
      questioned whether VR is capable of provoking psychophysiological symptoms of
      anxiety. Since psychophysiological arousal is considered a prerequisite for
      effective exposure treatment, this systematic review aims to evaluate the
      evidence for the potential of VR exposure to evoke and modulate
      psychophysiological fear reactions. METHODS: PubMed and PsycINFO/Academic Search
      Premier databases were searched. Thirty-eight studies investigating challenge or
      habituation effects were included. RESULTS: VR exposure does provoke
      psychophysiological arousal, especially in terms of electrodermal activity.
      Results on psychophysiological habituation in VR are inconclusive. Study design
      and methodological rigour vary widely. CONCLUSIONS: Despite several limitations,
      this review provides evidence that VR exposure elicits psychophysiological fear
      reactions in patients and healthy subjects, rendering VR a promising treatment
      for anxiety disorders, and a potent research tool for future investigations of
      psychophysiological processes and their significance during exposure treatment.

PMID- 24666249
TI  - Achievement of take-home dose privileges is associated with better-perceived
      sleep and with cognitive status among methadone maintenance treatment patients.
AB  - OBJECTIVES: Methadone maintenance treatment (MMT) patients may achieve up to a 2
      week privilege of methadone take-home doses (THD), which is associated with
      considerable responsibility. MMT patients are characterized as having poor sleep
      quality and low cognitive states. We studied sleep indices and cognitive status
      with respect to THD privileges. METHODS: A sample of 123 MMT patients stratified
      by THD groups was studied. Pittsburgh Sleep Quality Index (PSQI), Epworth
      Sleepiness Scale (ESS), and the cognitive Clock Drawing Test (CDT) were
      performed. RESULTS: Thirty-one of 123 patients never had any THD and 92 did (25
      had the maximum of 2 weeks). The never THD had history of longer duration of
      opiate usage and a shorter period in MMT. They had the highest rates of poor
      sleep (80.6%, PSQI > 5), daily sleepiness ("fall asleep while talking") (41.9%),
      and impaired cognitive status (58.1%, CDT < 3), while those who had 2-week
      privileges had the lowest (56, 8, and 28%, respectively). Logistic regression
      characterized THD patients as no-benzodiazepine and no-cocaine, short opiate
      usage duration, low ADHD scores, and no cognitive impairment (CDT = 3) and its
      interaction with treatment duration. CONCLUSION: Privileges that reflect
      patients' abstinence and rehabilitation were also expanded to be associated with
      better cognitive states. These finding confirm the THD dispensing performance.
      Including CDT as part of the decision for dispensing THD may be considered.

PMID- 24666251
TI  - Expression profiling of PPARgamma-regulated microRNAs in human subcutaneous and
      visceral adipogenesis in both genders.
AB  - Clinical evidence shows that visceral fat accumulation decreases whereas sc fat
      increases in patients treated with thiazolidinediones (TZDs), a type of
      peroxisome proliferator-activated receptor (PPAR)gamma agonist. To clarify the
      molecular mechanism of the differential effects of PPARgamma agonists on sc and
      visceral adipose, we investigated expression profiling of PPARgamma-regulated
      micro-RNAs (miRNAs) using miRNA microarray. The level of 182 miRNAs changed in
      human sc adipose treated with pioglitazone, whereas only 46 miRNAs changed in
      visceral adipose. Among these miRNAs, 27 miRNAs changed in both human sc and
      visceral adipocytes. Specifically, 7 miRNAs changed at the same direction in sc
      and visceral adipocytes, whereas 20 miRNAs changed at opposite directions in
      these two fat depots. Bioinformatics analysis showed that these miRNAs and the
      predicted target genes were involved in TGF-beta-, Wnt/beta-catenin-, and insulin
      signaling pathways and related to metabolic regulation or cell cycle. Among the
      miRNAs changed at the same direction in sc and visceral adipocytes, miR-378,
      located in the first intron of PPARgamma coactivator 1beta (PGC1beta), was
      coordinately expressed with PGC1beta during adipogenesis. Moreover, miR-378 and
      PGC1beta were both up-regulated by PPARgamma agonist. We also provided evidence
      that miR-378 promoted adipogenesis in sc fat, but not in visceral fat. These
      results display miRNAs expression profiling altered in sc and visceral
      adipogenesis regulated by PPARgamma and suggest a potential mechanism underlying
      the differential effects of TZDs on the 2 fat depot accumulations. 

PMID- 24666252
TI  - Contribution of CD39 to the immunosuppressive microenvironment of acute myeloid
      leukaemia at diagnosis.

PMID- 24666250
TI  - Historical control data on developmental toxicity studies in rodents.
AB  - Historical control data on rodent developmental toxicity studies, performed
      between 1994 and 2010, were obtained from 19 laboratories in Japan, including 10
      pharmaceutical and chemical companies and nine contract research organizations.
      Rats, mice, and hamsters were used for developmental toxicity studies. Data
      included maternal reproductive findings at terminal cesarean sections and fetal
      findings including the spontaneous incidences of external, visceral, and skeletal
      anomalies. No noticeable differences were observed in maternal reproductive data
      between laboratories. Inter-laboratory variations in the incidences of fetuses
      with anomalies appeared to be due to differences in the selection of observation
      parameters, observation criteria, classification of the findings, and terminology
      of fetal alterations. Historical control data are useful for the appropriate
      interpretation of experimental results and evaluation of the effects of chemical
      on reproductive and developmental toxicities. 

PMID- 24666253
TI  - Particle-associated extracellular enzyme activity and bacterial community
      composition across the Canadian Arctic Ocean.
AB  - Microbial enzymatic hydrolysis of marine-derived particulate organic carbon (POC)
      can be a dominant mechanism for attenuating carbon flux in cold Arctic waters
      during spring and summer. Whether this mechanism depends on composition of
      associated microbial communities and extends into other seasons is not known.
      Bacterial community composition (BCC) and extracellular enzyme activity (EEA, for
      leucine aminopeptidases, glucosidases and chitobiases) were measured on small
      suspended particles and potentially sinking aggregates collected during fall from
      waters of the biologically productive North Water and river-impacted Beaufort
      Sea. Although other environmental variables appeared influential, both BCC and
      EEA varied along a marine productivity gradient in the two regions. Aggregates
      harbored the most distinctive bacterial communities, with a small number of taxa
      driving differences between particle-size classes (1.0-60 and > 60 MUm) and free
      living bacteria (0.2-1.0 MUm). Significant relationships between patterns in
      particle-associated BCC and EEA suggest strong links between these two variables.
      Calculations indicated that up to 80% of POC in the euphotic zone of the North
      Water, and 20% in the Beaufort Sea, may be hydrolyzed enzymatically, underscoring
      the importance of this mechanism in attenuating carbon fluxes in Arctic waters
      even as winter approaches.

PMID- 24666254
TI  - A review of the solitary cutaneous T-cell lymphomas.
AB  - Cutaneous T-cell lymphomas (CTCL) account for almost 65-92% of all cutaneous
      lymphomas, many of which usually present with multiple lesions. However, a number
      of well-recognized and rare types of CTCL, including mycosis fungoides, can
      present in isolated fashion. These solitary lesions often run a relatively
      indolent clinical course but often pose diagnostic difficulties. We review
      histopathologically challenging solitary cutaneous T-cell lymphomas, including
      criteria for diagnosis, clinical course and prognosis, particularly for primary
      cutaneous CD4+ small/medium pleomorphic lymphoma and indolent CD8+ lymphoid
      proliferation of acral sites. In addition, we suggest an algorithm and
      nomenclature to aid in the diagnosis of such problematic lesions. 

PMID- 24666255
TI  - Formononetin induces apoptosis in PC-3 prostate cancer cells through enhancing
      the Bax/Bcl-2 ratios and regulating the p38/Akt pathway.
AB  - Formononetin (FN), a bioactive component extracted from the red clover (Trifolium
      pratense L.), has been long used for treating carcinomas in China. In the present
      study, we aim to investigate the potential therapeutical effects of FN on cell
      line of prostatic adenocarcinoma (PC-3) and human prostate epithelial cells
      (RWPE1). These findings indicated that FN significantly inhibited the cell growth
      of PC-3 in a dose-dependent manner, but no such effect was observed in RWPE1
      cells. The apoptotic counts were effectively increased following the treatments
      as shown in flow cytometry. The results from Western blotting assay suggested
      that FN treatment contributed to the reduced Bcl-2 protein level and the elevated
      Bax expression in PC-3 cells, thereby resulting in the increasing Bax/Bcl-2
      ratios. Furthermore, the phosphorylated level of p38 in PC-3 cells was activated
      through the FN treatment, whereas the endogenous Akt phosphorylation was blocked.
      Collectively, our findings demonstrate that FN exerts the anticarcinogenic effect
      on prostate cancer in vitro, in which the underlying mechanisms are associated
      with enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway, thus
      triggering apoptosis in tumor cells. 

PMID- 24666256
TI  - Illness self-concept in Type 1 diabetes: a cross-sectional view on clinical,
      demographic, and psychosocial correlates.
AB  - The present study assessed the centrality of one's illness self-concept, or the
      degree to which chronic illness intrudes upon one's self, in a sample of 478 18
      35-year-old patients with Type 1 diabetes. Confirmatory factor analysis indicated
      that illness self-concept centrality was a one-dimensional construct, despite the
      fact that three constituting components (i.e. pervasiveness, directionality, and
      illness self-consciousness) have been forwarded. Further, important demographic
      and clinical correlates of illness self-concept were identified: women,
      unemployed individuals, individuals with a lower educational level, and patients
      with an insulin pump had a more central illness self-concept. Finally, a series
      of correlation and regression analyses indicated that, despite the fact that
      illness self-concept centrality was negatively related to emotional stability,
      self-esteem, and diabetes integration, and positively to perceived consequences
      of diabetes, illness self-concept had unique predictive value over and above
      these variables for problem areas in diabetes and depressive symptoms.
      Implications and suggestions for future research are outlined.

PMID- 24666257
TI  - Differential clinical characteristics, treatment response and prognosis of
      locally advanced adenocarcinoma/adenosquamous carcinoma and squamous cell
      carcinoma of cervix treated with definitive radiotherapy.
AB  - OBJECTIVE: To compare tumor characteristics and clinical outcome of patients with
      cervical locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and
      squamous cell carcinoma (SCC). DESIGN: Retrospective study. SETTING: National
      Taiwan University Hospital, Taipei, Taiwan. POPULATION: All patients with
      cervical SCC (n = 35), AC or ASC (n = 194) with FIGO stage >=IIB who received
      definitive radiotherapy or concurrent chemoradiotherapy (CCRT) from January 1995
      to December 2009. METHOD: Medical and histopathological record review. MAIN
      OUTCOME MEASURES: Progression-free survival (PFS), local recurrence-free
      survival, distant metastasis-free survival, and overall survival (OS). RESULTS:
      Compared with the SCC subgroup, patients with AC/ASC were significantly younger
      (p = 0.007), more of them without clinical symptoms were diagnosed by abnormal
      Pap smear findings (p = 0.043), and less responded to treatment (p = 0.018).
      After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year
      PFS (30.0% vs. 47.6%, p = 0.044), worse 5-year distant metastasis-free survival
      (41.5% vs. 69.9%, p = 0.005), and trends toward worse 5-year local recurrence
      free survival (64.4% vs. 76.2%, p = 0.165) and worse 5-year OS (41.3% vs. 58.1%,
      p = 0.090) than patients with SCC. In univariate analysis, early FIGO stage and
      complete treatment response were significantly associated with PFS and OS.
      Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy
      fractions >85 Gy were significantly associated with better PFS, and CCRT was
      significantly associated with better OS. In multivariate analysis, complete
      treatment response and early FIGO stage remained significant factors for
      predicting better PFS and OS. CONCLUSIONS: Cervical AC/ASC may be more aggressive
      than is SCC. For cervical AC/ASC, more comprehensively effective treatments are
      warranted.

PMID- 24666258
TI  - Rapid prototyping of electrochromatography chips for improved two-photon excited
      fluorescence detection.
AB  - In the present study, we introduce two-photon excitation at 532 nm for label-free
      fluorescence detection in chip electrochromatography. Two-photon excitation at
      532 nm offers a promising alternative to one-photon excitation at 266 nm, as it
      enables the use of economic chip materials instead of fused silica. In order to
      demonstrate these benefits, one-photon and two-photon induced fluorescence
      detection are compared in different chip layouts and materials with respect to
      the achievable sensitivity in the detection of polycyclic aromatic hydrocarbons
      (PAHs). Customized chromatography chips with cover or bottom slides of different
      material and thickness are produced by means of a rapid prototyping method based
      on liquid-phase lithography. The design of thin bottom chips (180 MUm) enables
      the use of high-performance immersion objectives with low working distances,
      which allows one to exploit the full potential of two-photon excitation for a
      sensitive detection. The developed method is applied for label-free analysis of
      PAHs separated on a polymer monolith inside polymer glass sandwich chips made
      from fused silica or soda-lime glass. The obtained limits of detection range from
      40 nM to 1.95 MUM, with similar sensitivities in fused silica thin bottom chips
      for one-photon and two-photon excitation. In deep-UV non- or less-transparent
      devices two-photon excitation is mandatory for label-free detection of aromatics
      with high sensitivity. 

PMID- 24666259
TI  - Supramolecular chemistry of p-sulfonatocalix[n]arenes and its biological
      applications.
AB  - CONSPECTUS: Developments in macrocyclic chemistry have led to supramolecular
      chemistry, a field that has attracted increasing attention among researchers in
      various disciplines. Notably, the discoveries of new types of macrocyclic hosts
      have served as important milestones in the field. Researchers have explored the
      supramolecular chemistry of several classical macrocyclic hosts, including crown
      ethers, cyclodextrins, calixarenes, and cucurbiturils. Calixarenes represent a
      third generation of supramolecular hosts after cyclodextrins and crown ethers.
      Easily modified, these macrocycles show great potential as simple scaffolds to
      build podand-like receptors. However, the inclusion properties of the cavities of
      unmodified calixarenes are not as good as those of other common macrocycles.
      Calixarenes require extensive chemical modifications to achieve efficient endo
      complexation. p-Sulfonatocalix[n]arenes (SCnAs, n = 4-8) are a family of water
      soluble calixarene derivatives that in aqueous media bind to guest molecules in
      their cavities. Their cavities are three-dimensional and pi-electron-rich with
      multiple sulfonate groups, which endow them with fascinating affinities and
      selectivities, especially toward organic cations. They also can serve as
      scaffolds for functional, responsive host-guest systems. Moreover, SCnAs are
      biocompatible, which makes them potentially useful for diverse life sciences and
      pharmaceutical applications. In this Account, we summarize recent work on the
      recognition and assembly properties unique to SCnAs and their potential
      biological applications, by our group and by other laboratories. Initially
      examining simple host-guest systems, we describe the development of a series of
      functional host-guest pairs based on the molecular recognition between SCnAs and
      guest molecules. Such pairs can be used for fluorescent sensing systems,
      enzymatic activity assays, and pesticide detoxification. Although most
      macrocyclic hosts prevent self-aggregation of guest molecules, SCnAs can induce
      self-aggregation. Researchers have exploited calixarene-induced aggregation to
      construct supramolecular binary vesicles. These vesicles respond to internal and
      external stimuli, including temperature changes, redox reactions, additives, and
      enzymatic reactions. Such structures could be used as drug delivery vehicles.
      Although several biological applications of SCnAs have been reported, this field
      is still in its infancy. Continued exploration of the supramolecular chemistry of
      SCnAs will not only improve the existing biological functions but also open new
      avenues for the use of SCnAs in the fields of biology, biotechnology, and
      pharmaceutical research. In addition, we expect that other interdisciplinary
      research efforts will accelerate developments in the supramolecular chemistry of
      SCnAs.

PMID- 24666260
TI  - Identification of the phenolic compounds contributing to antibacterial activity
      in ethanol extracts of Brazilian red propolis.
AB  - The purpose of this study is to identify the quantity and antibacterial activity
      of the individual phenolic compounds in Brazilian red propolis. Quantitative
      analysis of the 12 phenolic compounds in Brazilian red propolis was carried out
      using reversed-phase high-performance liquid chromatography. The main phenolic
      compounds in Brazilian red propolis were found to be (3S)-vestitol (1), (3S)
      neovestitol (2) and (6aS,11aS)-medicarpin (4) with quantities of 72.9, 66.9 and
      30.8 mg g of ethanol extracts(- 1), respectively. Moreover, the antibacterial
      activities of each compound against Staphylococcus aureus, Bacillus subtilis and
      Pseudomonas aeruginosa were evaluated by measuring the minimum inhibitory
      concentrations. In particular, compound 4 exhibited the most potent antibacterial
      activity among all the assayed compounds against selected bacteria, indicating
      that 4 is the most active compound in Brazilian red propolis extracts. Thus,
      Brazilian red propolis may be used as food additives and pharmaceuticals to
      protect against bacteria.

PMID- 24666261
TI  - Tuning model drug release and soft-tissue bioadhesion of polyester films by
      plasma post-treatment.
AB  - Plasma treatments are investigated as a post-production method of tuning drug
      release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA
      films were treated under varying conditions by controlling gas flow rate,
      composition, treatment time, and radio frequency (RF) power. In vitro release of
      the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was
      tunable by controlling RF power; an increase of 65% cumulative release is
      reported compared to controls. Bioadhesion was sensitive to RF power and
      treatment time, assessed using ex vivo shear-stress tests with wetted swine
      aorta. We report a maximum bioadhesion ~6-fold that of controls and 5-fold that
      of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post
      treatment is the activation of a hydrophobic polyester film for bioadhesion,
      which can be quenched, while simultaneously tuning drug-release kinetics. This
      exemplifies the promise of plasma post-treatment for in-clinic bioadhesive
      activation, along with technological advancements, i.e., atmospheric plasma and
      hand-held "plasma pencils". 

PMID- 24666262
TI  - Epidemiology and prevention of carbapenem-resistant Enterobacteriaceae in the
      United States.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant organisms
      with few treatment options that cause infections associated with substantial
      morbidity and mortality. CRE outbreaks have been increasingly reported worldwide
      and are mainly due to the emergence and spread of strains that produce
      carbapenemases. In the United States, transmission of CRE is primarily driven by
      the spread of organisms carrying the Klebsiella pneumoniae carbapenemase enzyme,
      but other carbapenemase enzymes, such as the New-Delhi metallo-beta-lactamase,
      have also emerged. Currently recommended control strategies for healthcare
      facilities include the detection of patients infected or colonized with CRE and
      implementation of measures to prevent further spread. In addition to efforts in
      individual facilities, effective CRE control requires coordination across all
      healthcare facilities in a region. This review describes the current epidemiology
      and surveillance of CRE in the United States and the recommended approach to
      prevention. 

PMID- 24666263
TI  - Anticarcinogenic effects of products of heat-processed ginsenoside Re, a major
      constituent of ginseng berry, on human gastric cancer cells.
AB  - Ginsenoside Re is a triol type triterpene glycoside and is abundantly present in
      ginseng berry. In the present study, we verified that ginsenoside Re can be
      transformed into less-polar ginsenosides, namely, Rg2, Rg6, and F4, by heat
      processing. The products of heat-processed ginsenoside Re inhibited
      phosphorylation of CDK2 at Thr160 by upregulation of p21 level, resulting in S
      phase arrest. The products of heat-processed ginsenoside Re also activated
      caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of
      caspase-3, in a dose-dependent manner. Concurrently, alteration of mitochondrial
      factors such as Bcl-2 and Bax was also observed. Moreover, pretreatment with Z
      VAD-fmk abrogated caspase-8, -9, and -3 activations by the products of heat
      processed ginsenoside Re. We further confirmed that the anticancer effects of the
      products of heat-processed ginsenoside Re in AGS cells are mainly mediated via
      generation of less-polar ginsenosides Rg6 and F4.

PMID- 24666265
TI  - Salmonella survival and differential expression of fatty acid biosynthesis
      associated genes in a low-water-activity food.
AB  - The purpose of this study was to investigate the difference in expression of
      fatty acid biosynthesis genes and survival of different serotypes of Salmonella
      when incubated in a low-water-activity (aw ) food over a 14-day period.
      Stationary cells of five strains of Salmonella enterica belonging to 3 different
      serovars (Typhimurium ATCC 2486, Enteritidis H4267, Tennessee ARI-33, Tennessee
      S13952 and Tennessee K4643) were inoculated into granular sugar (aW   = 0.50) and
      held aerobically over a 14-day period at 25 degrees C. Survival was determined by
      enumerating colonies on TSA and XLT-4 plates at 0, 1, 3, 5, 7 and 14 days.
      Correspondingly, gene expression was evaluated for three selected genes involved
      in fatty acid biosynthesis and modification (fabA, fabD and cfa). After 14 days
      of incubation, the population was reduced from 2.29 to 3.36 log for all five
      strains. Salmonella Tennessee ARI-33 and Salm. Tennessee K4643 displayed greater
      survival than Salm. Typhimurium and Salm. Enteritidis. The increased expression
      of the cfa gene (involved in cyclopropane fatty acid biosynthesis) over 14 days
      was found associated with strains with a lower survival rate. The fabA gene
      (involved in unsaturated fatty acid biosynthesis) was observed up-regulated for
      all strains for at least one sampling time and for Salm. Tennessee ARI-33 for all
      time points tested, suggesting its potential role in enhancing Salmonella
      survival in low aw foods. SIGNIFICANCE AND IMPACT OF THE STUDY: Numerous
      outbreaks of salmonellosis associated with low-water-activity foods have been
      reported. Therefore, the adaptive mechanisms utilized by Salmonella to survive in
      low-water-activity foods for prolonged periods of time need to be better
      understood. The results in this study showed that low-water-activity environments
      increase expression of gene fabA, which is involved in unsaturated fatty acid
      biosynthesis of Salmonella, while the increased expression of cfa, associated
      with cyclopropane fatty acid synthesis, was associated with decreased survival
      over 14 days.

PMID- 24666264
TI  - Sorghum (Sorghum bicolor) varieties adopt strongly contrasting strategies in
      response to drought.
AB  - Sorghum is one of the most drought tolerant crops but surprisingly, little is
      known about the mechanisms achieving this. We have compared physiological and
      biochemical responses to drought in two sorghum cultivars with contrasting
      drought tolerance. These closely related cultivars have starkly contrasting
      responses to water deficit. In the less tolerant Samsorg 40, drought induced
      progressive loss of photosynthesis. The more drought tolerant Samsorg 17
      maintained photosynthesis, transpiration and chlorophyll content until the most
      extreme conditions. In Samsorg 40, there was a highly specific down-regulation of
      selected proteins, with loss of PSII and Rubisco but maintenance of PSI and
      cytochrome b6 f, allowing plants to maintain ATP synthesis. The nitrogen released
      allows for accumulation of glycine betaine and proline. To the best of our
      knowledge, this is the first example of specific reengineering of the
      photosynthetic apparatus in response to drought. In contrast, in Samsorg 17 we
      detected no substantial change in the photosynthetic apparatus. Rather, plants
      showed constitutively high soluble sugar concentration, enabling them to maintain
      transpiration and photosynthesis, even in extremely dry conditions. The
      implications for these strikingly contrasted strategies are discussed in relation
      to agricultural and natural systems. 

PMID- 24666266
TI  - Complications of endoscopic ultrasound-guided needle aspiration.

PMID- 24666267
TI  - The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment
      in metastatic colorectal cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: In metastatic colorectal cancer, mutation testing for KRAS exon 2 is
      widely implemented to select patients with wild-type tumors for treatment with
      the monocloncal anti-EGFR antibodies cetuximab and panitumumab. The added
      predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR
      pathways in colorectal cancer is uncertain, which led us to systematically review
      the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and
      PTEN in relation to the clinical benefit from anti-EGFR treatment. METHODS: In
      total, 22 studies that include 2395 patients formed the basis for a meta-analysis
      on alterations in KRAS exons 3 and 4, NRAS, BRAF, and PIK3CA and PTEN and outcome
      of anti-EGFR treatment. Odds ratios for objective response rate (ORR) and hazard
      ratios (HR) for progression-free survival (PFS) and overall survival (OS) were
      calculated. RESULTS: Mutations in KRAS exons 3 and 4, BRAF, PIK3CA and non
      functional PTEN (mutations or loss of protein expression) significantly predicted
      poor ORR (OR = 0.26, OR = 0.29, OR = 0.39, and OR = 0.41, respectively).
      Significantly shorter PFS applied to mutations in KRAS exons 3 and 4 (HR = 2.19),
      NRAS (HR = 2.30) and BRAF (HR = 2.95) and non-functional PTEN (HR = 1.88).
      Significantly shorter OS applied to mutations in KRAS exons 3 and 4 (HR = 1.78),
      NRAS (HR = 1.85), BRAF (HR = 2.52), PIK3CA (HR = 1.43) and alterations in PTEN
      (HR = 2.09). CONCLUSIONS: Meta-analysis suggests that mutations in KRAS exons 3
      and 4, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti
      EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should
      be implemented for prediction of clinical benefit from anti-EGFR antibodies in
      metastatic colorectal cancer.

PMID- 24666269
TI  - Effect of root morphology on biomechanical behaviour of premolars associated with
      abfraction lesions and different loading types.
AB  - The aim of this study was to investigate the biomechanical behaviour of maxillary
      premolar teeth regarding root morphology and abfraction depth, submitted to axial
      and oblique occlusal load. The investigation was conducted using 3D finite
      element analysis and strain gauge test. Sound maxillary premolar single and
      double root were selected for 3D model generation. The teeth were scanned for
      external morphology data acquisition. The 3D geometry was stored in *.STL and
      exported to Bio-CAD software (Rhinoceros-3D) to model generation. Mesh
      generation, mechanical properties and boundary conditions were performed in
      finite element software (Femap, Noran Engineering, USA). Twelve models were
      generated: sound tooth, 1.25 and 2.5 mm abfraction teeth. 100N compressive static
      load was applied: axially and 45 degrees  angle to the long axis on the palatine
      surface of the buccal cusp. Two strain gauges were bonded on the teeth mounted in
      a mechanical testing machine. Von Mises criterion showed that the double-root
      teeth associated with 2.5 mm abfraction and oblique loading presented higher
      stress values. Axial loading associated with single-root teeth propitiated the
      lowest stress rates. Double root sound 1.25 and 2.5 mm abfraction teeth
      associated with oblique loading showed the highest strain values (MUS): 692.6,
      1043.31 and 1236.14, respectively. Single root sound 1.25 and 2.5 mm abfraction
      teeth associated with oblique loading showed 467.10, 401.51 and 420.98 strain
      values, respectively. Axial loading showed lower strain rates, ranging from
      136.12 to 366.91. The association of deep lesions, oblique loading and double
      root tooth promoted higher stress and strain concentration.

PMID- 24666270
TI  - Leucocyte telomere length in patients with sickle cell disease.

PMID- 24666268
TI  - Minimizing adverse events while maintaining clinical improvement in a pediatric
      attention-deficit/hyperactivity disorder crossover trial with dextroamphetamine
      and methylphenidate.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the availability
      of both dextroamphetamine and methylphenidate provides an opportunity to minimize
      adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD)
      stimulant trial. METHODS: Thirty-six medication-naive children 9-14 years of age,
      diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks
      of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned,
      counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by
      parents, was used to assess adverse events. SERS were available for 34 children,
      and data were analyzed both at the group and the single-subject level. RESULTS:
      The side-effect profiles of dextroamphetamine and methylphenidate appeared
      similar at the group level. Overall, insomnia and decreased appetite were the
      only adverse events associated with the stimulants as compared with placebo. No
      significant increase from placebo to stimulant conditions was detected on SERS
      items reflecting emotional symptoms. Furthermore, dextroamphetamine and
      methylphenidate did not differ from each other on any SERS item, except that
      dextroamphetamine was associated with higher severity of "insomnia" and a higher
      prevalence of "unusually happy." Single-subject analyses showed that one or more
      adverse events were reported in 14 children (41%), and were evenly distributed
      between those with dextroamphetamine as the drug that showed the greatest
      reduction in their ADHD symptoms ("best drug") and those with methylphenidate as
      their best drug. Among children in whom both stimulants were associated with a
      decrease in ADHD symptoms, a clinically valid difference between the two
      stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In
      these children, the availability of both stimulants provided an opportunity to
      minimize adverse events, while maintaining a reduction in ADHD symptoms.
      CONCLUSIONS: The availability of both dextroamphetamine and methylphenidate may
      contribute to minimize adverse events in a subsample of children in pediatric
      ADHD stimulant trials. CLINICAL TRIALS REGISTRY: The study was first registered
      in clinical trials September 28, 2010. Clinical Trials.gov Identifier:
      NCT01220440.

PMID- 24666271
TI  - Subcellular localization, interactions and dynamics of the phage-shock protein
      like Lia response in Bacillus subtilis.
AB  - The liaIH operon of Bacillus subtilis is the main target of the envelope stress
      inducible two-component system LiaRS. Here, we studied the localization,
      interaction and cellular dynamics of Lia proteins to gain insights into the
      physiological role of the Lia response. We demonstrate that LiaI serves as the
      membrane anchor for the phage-shock protein A homologue LiaH. Under non-inducing
      conditions, LiaI locates in highly motile membrane-associated foci, while LiaH is
      dispersed throughout the cytoplasm. Under stress conditions, both proteins are
      strongly induced and colocalize in numerous distinct static spots at the
      cytoplasmic membrane. This behaviour is independent of MreB and does also not
      correlate with the stalling of the cell wall biosynthesis machinery upon
      antibiotic inhibition. It can be induced by antibiotics that interfere with the
      membrane-anchored steps of cell wall biosynthesis, while compounds that inhibit
      the cytoplasmic or extracytoplasmic steps do not trigger this response. Taken
      together, our data are consistent with a model in which the Lia system scans the
      cytoplasmic membrane for envelope perturbations. Upon their detection, LiaS
      activates the cognate response regulator LiaR, which in turn strongly induces the
      liaIH operon. Simultaneously, LiaI recruits LiaH to the membrane, presumably to
      protect the envelope and counteract the antibiotic-induced damage. 

PMID- 24666272
TI  - Supermarket medicine by proxy.

PMID- 24666274
TI  - Heparin solution for maintaining peripheral venous catheter patency in children:
      a survey of current practice in Italian pediatric units.
AB  - BACKGROUND: Prolonging the duration of peripheral venous catheters (PVC) as long
      as possible in children is a nursing priority. However, available studies provide
      conflicting evidence on what kind of flush/lock solution should be used to
      increase the life of PVCs in children. OBJECTIVES: To describe the clinical
      behavior of nurses working in Italian pediatric units with regards to PVCs
      flushing and locking practices. METHODS: Cross-sectional study. Nurses were
      invited to participate using the network of the Italian Society of Pediatric
      Nursing Science. Those participating completed an online questionnaire available
      on a website established for this specific purpose. Results: 405 questionnaires
      were completed. RESULTS: The majority of nurses reported using Normal saline
      solution (NS) to flush 22 gauge PVCs: 77.6% in children up to 6 months of age,
      74.7% in children 6 months to 2 years, and 74.6% in children over 2 years. Nurses
      tend to use heparin solutions (HS) more frequently when a smaller gauge PVC is
      used (24 instead of 22) and when access is less frequent. The use of HS for PVC
      lock is more common in onco-hematology units (54.5% in children over 6 months
      with 24 gauge PVC), pediatric surgery units (35%), and in short-stay units
      (55.6%), whereas NS is used more frequently in Intensive care units (9.4%) and
      neonatology units (12.2%). CONCLUSION: Although the majority of respondents use
      NS, we found a high variability in practices among Italian nurses. More research
      on the effectiveness and safety of HS in maintaining the patency of PVCs is
      needed.

PMID- 24666273
TI  - Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine.
AB  - This population-based descriptive epidemiology study demonstrates that rates of
      conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia
      in the Rivne province of Ukraine are among the highest in Europe. The province is
      200 km distant from the Chornobyl site and its northern half, a region known as
      Polissia, is significantly polluted by ionizing radiation. The rates of neural
      tube defects, microcephaly and microphthalmia in Polissia are statistically
      significantly higher than in the rest of the province. A survey of at-birth head
      size showed that values were statistically smaller in males and females born in
      one Polissia county than among neonates born in the capital city. These
      observations provide clues for confirmatory and cause-effect prospective
      investigations. The strength of this study stems from a reliance on international
      standards prevalent in Europe and a decade-long population-based surveillance of
      congenital malformations in two distinct large populations. The limitations of
      this study, as those of other descriptive epidemiology investigations, is that
      identified cause-effect associations require further assessment by specific
      prospective investigations designed to address specific teratogenic factors. 

PMID- 24666277
TI  - Iron-catalyzed arene alkylation reactions with unactivated secondary alcohols.
AB  - A simple, iron-based catalytic system allows for the inter- and intramolecular
      arylation of unactivated secondary alcohols. This transformation expands the
      substrate scope beyond the previously required activated alcohols and proceeds
      under mild reaction conditions, tolerating air and moisture. Furthermore, the use
      of an enantioenriched secondary alcohol provides an enantioenriched product for
      the intramolecular reaction, thereby offering a convenient approach to nonracemic
      products. 

PMID- 24666275
TI  - The effect of types I and III interferons on adrenocortical cells and its
      possible implications for autoimmune Addison's disease.
AB  - Autoimmune Addison's disease (AAD) is caused by selective destruction of the
      hormone-producing cells of the adrenal cortex. As yet, little is known about the
      potential role played by environmental factors in this process. Type I and/or
      type III interferons (IFNs) are signature responses to virus infections, and have
      also been implicated in the pathogenesis of autoimmune endocrine disorders such
      as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and
      exacerbation of established or subclinical disease, as well as the induction of
      autoantibodies associated with AAD, have been reported following therapeutic
      administration of type I IFNs. We therefore hypothesize that exposure to such
      IFNs could render the adrenal cortex susceptible to autoimmune attack in
      genetically predisposed individuals. In this study, we investigated possible
      immunopathological effects of type I and type III IFNs on adrenocortical cells in
      relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on
      NCI-H295R adrenocortical carcinoma cells and potentiated IFN-gamma- and
      polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion.
      Furthermore, we observed increased expression of human leucocyte antigen (HLA)
      class I molecules and up-regulation of 21-hydroxylase, the primary antigenic
      target in AAD. We propose that these combined effects could serve to initiate or
      aggravate an ongoing autoimmune response against the adrenal cortex in AAD. 

PMID- 24666278
TI  - The validity of the variable "NICU admission" as an outcome measure for neonatal
      morbidity: a retrospective study.
AB  - OBJECTIVE: To determine whether "neonatal intensive care unit (NICU) admission"
      is a valid surrogate outcome measure to assess neonatal condition in clinical
      studies. DESIGN: Retrospective study. SETTING: Tertiary hospital in the
      Netherlands. POPULATION: Neonates admitted to NICU during a 10-year period.
      Inclusion was restricted to singletons born beyond 37 weeks of gestation, and
      admitted to NICU in the first 24 h for delivery-related morbidity. METHODS:
      Patient characteristics and admission data were compared for four groups based on
      the line of care during delivery, i.e. home birth (Ia), midwife-led hospital
      delivery (Ib), secondary care (II), tertiary care (III). MAIN OUTCOME MEASURES:
      Percentage of neonates/infants that died during NICU admission, diagnosis on
      admission, treatment received and a Neonatal Therapeutic Intervention Score
      System (NTISS). RESULTS: We studied 776 newborns (Ia 52, Ib 25, II 160, III 512,
      27 unknown). The mortality rate differed significantly (Ia 15%, Ib 12%, II 22%,
      III 1%, p < 0.01), as did the NTISS morbidity scores at admission [Ia 12.0 (6.0
      23.0), Ib 8.5 (6.3-10.0), II 21.0 (15.0-30.0), III 6.0 (4.0-9.0); p < 0.01],
      diagnosis at admission, received treatment and the duration of admission.
      CONCLUSIONS: The severity of neonatal illness after 37 weeks of gestation
      differed depending on the line of care in which they were born, with neonates
      born in secondary care consistently having the highest morbidity, and those born
      in tertiary care having the lowest. NICU admission should not be used as an
      outcome measure for neonatal morbidity, specifically not when comparing different
      birth settings.

PMID- 24666279
TI  - In situ observation on the dynamic process of evaporation and crystallization of
      sodium nitrate droplets on a ZnSe substrate by FTIR-ATR.
AB  - Sodium nitrate is a main component of aging sea salt aerosol, and its phase
      behavior has been studied repeatedly with wide ranges observed in the
      efflorescence relative humidity (RH) in particular. Studies of the efflorescence
      dynamics of NaNO3 droplets deposited on a ZnSe substrate are reported, using an
      in situ Fourier transform infrared attenuated total reflection (FTIR-ATR)
      technique. The time-dependence of the infrared spectra of NaNO3 aerosols
      accompanying step changes in RH have been measured with high signal-to-noise
      ratio. From the IR difference spectra recorded, changes of the time-dependent
      absorption peak area of the O-H stretching band (nu-OH, ~3400 cm(-1)) and the
      nitrate out-of-plane bending band (nu2-NO3(-), ~836 cm(-1)) are obtained. From
      these measurements, changes in the IR signatures can be attributed to crystalline
      and solution phase nitrate ions, allowing the volume fraction of the solution
      droplets that have crystallized to be determined. Then, using these clear
      signatures of the volume fraction of droplets that have yet to crystallize, the
      homogeneous and heterogeneous nucleation kinetics can be studied from
      conventional measurements using a steady decline in RH. The nucleation rate
      measurements confirm that the rate of crystallization in sodium nitrate droplets
      is considerably less than in ammonium sulfate droplets at any particular degree
      of solute supersaturation, explaining the wide range of efflorescence RHs
      observed for sodium nitrate in previous studies. We demonstrate that studying
      nucleation kinetics using the FTIR-ATR approach has many advantages over
      brightfield imaging studies on smaller numbers of larger droplets or measurements
      made on single levitated particles. 

PMID- 24666280
TI  - Enzyme catalytic efficiency: a function of bio-nano interface reactions.
AB  - Biocatalyst immobilization onto carbon-based nanosupports has been implemented in
      a variety of applications ranging from biosensing to biotransformation and from
      decontamination to energy storage. However, retaining enzyme functionality at
      carbon-based nanosupports was challenged by the non-specific attachment of the
      enzyme as well as by the enzyme-enzyme interactions at this interface shown to
      lead to loss of enzyme activity. Herein, we present a systematic study of the
      interplay reactions that take place upon immobilization of three pure enzymes
      namely soybean peroxidase, chloroperoxidase, and glucose oxidase at carbon-based
      nanosupport interfaces. The immobilization conditions involved both single and
      multipoint single-type enzyme attachment onto single and multi-walled carbon
      nanotubes and graphene oxide nanomaterials with properties determined by Fourier
      transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDX),
      scanning electron microscopy (SEM), and atomic force microscopy (AFM). Our
      analysis showed that the different surface properties of the enzymes as
      determined by their molecular mapping and size work synergistically with the
      carbon-based nanosupports physico-chemical properties (i.e., surface chemistry,
      charge and aspect ratios) to influence enzyme catalytic behavior and activity at
      nanointerfaces. Knowledge gained from these studies can be used to optimize
      enzyme-nanosupport symbiotic reactions to provide robust enzyme-based systems
      with optimum functionality to be used for fermentation, biosensors, or biofuel
      applications. 

PMID- 24666282
TI  - Bacillus subtilis spore protein SpoVAC functions as a mechanosensitive channel.
AB  - A critical event during spore germination is the release of Ca-DPA (calcium in
      complex with dipicolinic acid). The mechanism of release of Ca-DPA through the
      inner membrane of the spore is not clear, but proteins encoded by the Bacillus
      subtilis spoVA operon are involved in the process. We cloned and expressed the
      spoVAC gene in Escherichia coli and characterized the SpoVAC protein. We show
      that SpoVAC protects E. coli against osmotic downshift, suggesting that it might
      act as a mechanosensitive channel. Purified SpoVAC was reconstituted in
      unilamellar lipid vesicles to determine the gating mechanism and pore properties
      of the protein. By means of a fluorescence-dequenching assay, we show that SpoVAC
      is activated upon insertion into the membrane of the amphiphiles lysoPC and
      dodecylamine. Patch clamp experiments on E. coli giant spheroplast as well as
      giant unilamellar vesicles (GUVs) containing SpoVAC show that the protein forms
      transient pores with main conductance values of about 0.15 and 0.1 nS
      respectively. Overall, our data indicate that SpoVAC acts as a mechanosensitive
      channel and has properties that would allow the release of Ca-DPA and amino acids
      during germination of the spore. 

PMID- 24666283
TI  - Arcobacter spp. isolated from untreated domestic effluent.
AB  - Arcobacter butzleri and Arcobacter cryaerophilus were isolated from samples of
      raw untreated domestic sewage influent from nine separate wastewater treatment
      facilities in Cheshire, UK. This is the first report of Arcobacter spp. from
      sewage in the UK and suggests that Arcobacter spp. may be present in the human
      community. SIGNIFICANCE AND IMPACT OF THE STUDY: Studies have shown Arcobacter
      spp. to be present in domestic sewage in several European countries. This study
      supports previous findings with the first report of Arcobacter spp. in domestic
      sewage in the UK. This study suggests that Arcobacter spp. is present amongst
      local human populations, implicating it as an underestimated gastrointestinal
      pathogen in the UK and contributing to our understanding of this emerging
      pathogen and its presence within the UK. Providing a confirmation of the presence
      of Arcobacter in sewage, which supports previous studies, this paper will appeal
      to fellow researchers of Arcobacter, as well as healthcare and water treatment
      professionals concerned with microbiology, water safety and gastroenterology,
      potentially having a wide impact.

PMID- 24666281
TI  - Human cathelicidin LL-37 and its derivative IG-19 regulate interleukin-32-induced
      inflammation.
AB  - Human cathelicidin LL-37 protects against infections and endotoxin-induced
      inflammation. In a recent study we have shown that IG-19, an LL-37-derived
      peptide, protects in a murine model of arthritis. Cytokine interleukin-32 (IL-32)
      is elevated and directly associated with the disease severity of inflammatory
      arthritis. Therefore, in this study we examined the effects of LL-37 and IG-19 on
      IL-32-induced responses in human peripheral blood-derived mononuclear cells
      (PBMC) and macrophages. We showed that CD14(+) monocytes are the primary cells
      that produce pro-inflammatory tumour necrosis factor-alpha (TNF-alpha) following
      stimulation of PBMC with IL-32. We demonstrated that LL-37 and IG-19
      significantly suppress IL-32-induced production of pro-inflammatory cytokines,
      e.g. TNF-alpha and IL-1beta, without altering chemokine production. In contrast,
      LL-37 and IG-19 enhance the production of the anti-inflammatory cytokine IL-1RA.
      Further mechanistic studies revealed that LL-37 and IG-19 suppress IL-32-mediated
      phosphorylation of Fyn (Y420) Src kinase. In contrast, IL-32-mediated
      phosphorylation of AKT-1 (T308) and MKP-1 (S359) is not suppressed by the
      peptides. LL-37 and IG-19 alone induce the phosphorylation of MKP-1 (S359), which
      is a known negative regulator of inflammation. Furthermore, the peptides induce
      the activity of p44/42 mitogen-activated protein kinase, which is known to
      phosphorylate MKP-1 (S359). This is the first study to demonstrate the regulation
      of IL-32-induced inflammation by LL-37 and its derivative peptide IG-19. The
      mechanistic results from this study suggest that regulation of immune-mediated
      inflammation by these peptides may be controlled by the dual phosphatase MKP-1.
      We speculate that LL-37 and its derivatives may contribute to the control of
      immune-mediated inflammatory diseases. 

PMID- 24666284
TI  - HPC-1/syntaxin 1A and syntaxin 1B play distinct roles in neuronal survival.
AB  - Two types of syntaxin 1 isoforms, HPC-1/syntaxin 1A (STX1A) and syntaxin 1B
      (STX1B), are thought to have similar functions in exocytosis of synaptic
      vesicles. STX1A(-/-) mice which we generated previously develop normally,
      possibly because of compensation by STX1B. We produced STX1B(-/-) mice using
      targeted gene disruption and investigated their phenotypes. STX1B(-/-) mice were
      born alive, but died before postnatal day 14, unlike STX1A(-/-) mice.
      Morphologically, brain development in STX1B(-/-) mice was impaired. In
      hippocampal neuronal culture, the cell viability of STX1B(-/-) neurons was lower
      than that of WT or STX1A(-/-) neurons after 9 days. Interestingly, STX1B(-/-)
      neurons survived on WT or STX1A(-/-) glial feeder layers as well as WT neurons.
      However, STX1B(-/-) glial feeder layers were less effective at promoting survival
      of STX1B(-/-) neurons. Conditioned medium from WT or STX1A(-/-) glial cells had a
      similar effect on survival, but that from STX1B(-/-) did not promote survival.
      Furthermore, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 supported
      survival of STX1B(-/-) neurons. BDNF localization in STX1B(-/-) glial cells was
      disrupted, and BDNF secretion from STX1B(-/-) glial cells was impaired. These
      results suggest that STX1A and STX1B may play distinct roles in supporting
      neuronal survival by glia. Syntaxin 1A (STX1A) and syntaxin 1B (STX1B) are
      thought to have similar functions as SNARE proteins. However, we found that STX1A
      and STX1B play distinct roles in neuronal survival using STX1A(-/-) mice and
      STX1B(-/-) mice. STX1B was important for neuronal survival, possibly by
      regulating the secretion of neurotrophic factors, such as BDNF, from glial cells.

PMID- 24666285
TI  - Polymyxins for the treatment of extensively-drug-resistant Gram-negative
      bacteria: from pharmacokinetics to bedside.
AB  - The initial use of polymyxins, polymyxin B and colistin (administered as a pro
      drug colistin methanesulfonate sodium [CMS]), mostly relied on old
      pharmacokinetic (PK) studies that lacked appropriate methodology. In recent
      years, many PK studies in both animals and humans have provided more consistent
      evidence supporting better use of these invaluable antibiotics. However,
      translating preclinical data to clinical practice is not always an easy task and
      some may experience difficulties on how recent knowledge on polymyxins can be
      applied into the patients' care. Although many questions are still unresolved,
      there are consistent data able to improve clinical practice when prescribing
      initial and maintenance doses of both polymyxin B and CMS. Considering the
      importance of optimal use of polymyxins, this editorial discusses recent PK
      findings and how to take advantage of them at the bedside to improve the
      treatment of patient with extensively-drug-resistant Gram-negative bacterial
      infections. 

PMID- 24666286
TI  - Extended-spectrum beta-lactamase-producing Escherichia coli isolated from
      poultry: a review of current problems, illustrated with some laboratory findings.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has been
      documented in humans as well as in food-producing birds, including chickens, and
      for unknown reasons the prevalence has increased significantly during the last
      decade. With E. coli as a major opportunistic pathogen in chickens and with a
      potential for zoonotic transfer to human beings, ESBL-producing E. coli
      represents a major risk both to poultry production and to human health. This
      review presents some of the current problems with ESBL-producing E. coli in
      relation to poultry production, with a focus on chickens. To illustrate issues in
      relation to screening and typing, two case studies are included where one
      collection of ESBL-producing E. coli isolates was obtained from asymptomatic
      carrier chickens while the other was obtained from lesions in chickens. Pulsed
      field gel electrophoresis and multi-locus sequence typing revealed a highly
      heterogeneous population of ESBL-producing E. coli. All isolates harboured
      between one and three large plasmids (>100 kb). Among isolates associated with
      asymptomatic chickens, the ESBL types SHV and TEM dominated, while CTX-M-1
      dominated in disease-associated isolates. The isolates from diseased birds were
      occasionally of sequence types often associated with human infections, such as
      ST131. With improved tools to trace and screen for ESBL-producing E. coli at farm
      level, strategies can be selected that aim to reduce or eliminate the presence of
      ESBL-producing E. coli in poultry and poultry products meant for human
      consumption. 

PMID- 24666287
TI  - Synthesis and in vitro and in vivo evaluation of SiFA-tagged bombesin and RGD
      peptides as tumor imaging probes for positron emission tomography.
AB  - Gastrin-releasing-peptide (GRP)-receptors and alphavbeta3-integrins are widely
      discussed as potential target structures for oncological imaging with positron
      emission tomography (PET). Favored by the overexpression of receptors on the
      surface of tumor cells good imaging characteristics can be achieved with highly
      specific radiolabeled receptor ligands. PEGylated bombesin (PESIN) derivatives as
      specific GRP receptor ligands and RGD (one-letter codes for arginine-glycine
      aspartic acid) peptides as specific alphavbeta3 binders were synthesized and
      tagged with a silicon-fluorine-acceptor (SiFA) moiety. The SiFA synthon allows
      for a fast and highly efficient isotopic exchange reaction at room temperature
      giving the [(18)F]fluoride labeled peptides in up to 62% radiochemical yields
      (d.c.) and >=99% radiochemical purity in a total synthesis time of less than 20
      min. Using nanomolar quantities of precursor high specific activities of up to 60
      GBq MUmol(-1) were obtained. To compensate the high lipophilicity of the SiFA
      moiety various hydrophilic structure modifications were introduced leading to
      significantly reduced logD values. Competitive displacement experiments with the
      PESIN derivatives showed a 32 to 6 nM affinity to the GRP receptor on PC3 cells,
      and with the RGD peptides a 7 to 3 MUM affinity to the alphavbeta3 integrins on
      U87MG cells. All derivatives proved to be stable in human plasma over at least
      120 min. Small animal PET measurements and biodistribution studies revealed an
      enhanced and specific accumulation of the RGD peptide (18)F-SiFA-LysMe3-gamma
      carboxy-d-Glu-RGD (17) in the tumor tissue of U87MG tumor-bearing mice of 5.3%
      ID/g whereas the PESIN derivatives showed a high liver uptake and only a low
      accumulation in the tumor tissue of PC3 xenografts. Stability studies with
      compound 17 provided further information on its metabolism in vivo. These results
      altogether demonstrate that the reduction of the overall lipophilicity of SiFA
      tagged RGD peptides is a promising approach for the generation of novel potent
      (18)F-labeled imaging agents. 

PMID- 24666288
TI  - Significance of the imidazoline receptors in toxicology.
AB  - INTRODUCTION: The alpha-2 adrenergic (AA-2) receptor agonists and imidazolines
      are common exposures in the American Association of Poison Control Centers
      (AAPCC) National Poison Data System (NPDS). Although the interaction between the
      AA-2 receptor and imidazoline receptors has been extensively studied, it largely
      remains unknown to health-care professionals. This review describes these
      interactions and mechanisms by which agonists affect physiologic responses
      binding to these receptors. METHODS: Papers published in English from 1960 to
      2013 were retrieved from PubMed. A total of 323 original articles were identified
      and 173 were included. Background. The toxicity associated with clonidine (e.g.,
      bradycardia, miosis, and hypotension) is largely assumed to be secondary to the
      functional overlap of the AA-2 receptors and the mu receptors. However, the
      effects at the AA-2 receptor could not fully account for these symptoms.
      Subsequently, clonidine was found to produce its pharmacologic effect in the
      central nervous system (CNS) by interaction not only with the AA-2 receptor but
      also on selective imidazoline receptors. IMIDAZOLINE RECEPTORS: Since their
      discovery, three distinct classes of imidazoline receptors, also known as
      imidazoline binding sites or imidazoline/guanidinium receptive sites, have been
      characterized. Imidazoline-1 (I-1) receptors are involved in the hypotensive
      activity of clonidine and related compounds supporting the idea that the I-1
      receptors are upstream from the AA-2 receptor and work in tandem for its effect
      on blood pressure. Additionally, stimulation of N-type Calcium-2 channels, G
      protein inwardly rectifying potassium channel, adenosine receptors, phosphatidyl
      choline-specific phospholipase C, and nicotinic receptors have been implicated to
      be involved. Previous studies have shown that I-1 receptors may also be involved
      in other physiologic responses beyond cardiac function. Imidazoline-2 (I-2)
      receptors interact with monoamine oxidase A and monoamine oxidase B leading to
      research that has focused on the effect of I-2 receptors and depression and the
      suggestion of a possible antidepressant action of the imidazolines. I-2 receptor
      ligands may have substantial antinociceptive activity and work synergistically
      with opioids in acute pain. Imidazoline-3 (I-3) receptors are located on the
      pancreatic beta-cells and modulate glucose homeostasis. IMIDAZOLINE LIGANDS: Four
      endogenous compounds have been found to bind and include clonidine-displacing
      substance, agmatine, harmane, and imidazole acetic acid. Significant interest in
      developing new agents with higher selectivity and affinity for I-1 receptors has
      resulted. Toxicology. Alpha-2 adrenoceptor and imidazoline receptor agonists such
      as clonidine and tetrahydrozoline are common ingestions reported to poison
      control centers. The most common toxic effects of clonidine are similar to those
      of the over-the-counter imidazolines and include CNS depression, bradycardia,
      hypotension, respiratory depression, miosis, hypothermia, and hypertension (early
      and transient). Based on their structure and subsequent studies, imidazoline
      receptors seem to be the primary binding site for these chemicals. Case reports
      typically illustrate rapid onset of action with serious side effects following
      ingestion of relatively small amounts. These agents have been reportedly used in
      drug-assisted sexual assaults. CONCLUSION: Much of the toxicity associated with
      drugs such as clonidine, guanfacine, and tetrahydrozoline are due to their
      binding to imidazoline receptors. Knowledge of the imidazoline receptors may lead
      to new therapeutic agents and inform management of patients with imidazoline
      overdose.

PMID- 24666289
TI  - Polyphenols pattern and correlation with antioxidant activities of berries
      extracts from four different populations of Sicilian Sambucus nigra L.
AB  - Sambucus nigra L. (Caprifoliaceae) is wide spread in temperate and sub-tropical
      zones. The consumption of its berries has been associated with health benefits
      especially for its high content of natural antioxidants such as polyphenols, in
      particular anthocyanins. In this work we investigated the polyphenolic
      composition and the in vitro antioxidant activities (ABTS, DPPH, BCB and FRAP
      ferrozine (FRAP-FZ) assays) of S. nigra berries, collected in four different
      Sicilian areas (Italy). Elderberries are considered one of the fruits with
      highest anthocyanins content, the amount of phenolic compounds, other than
      anthocyanins, is approximately 1.5 times greater than the latter. The LC-MS
      analyses have revealed an opposite trend in the polyphenols pattern in Sicilian
      populations. Moreover, a statistical correlation was found between cyanidin-3
      sambubioside-5-glucoside and antioxidant activity evaluated by FRAP-FZ and ABTS
      assays. In conclusion, Sicilian S. nigra berries are appealing for its
      antioxidant potential and for its particularly high content of anthocyanins. 

PMID- 24666290
TI  - MSX2 Gene Duplication in a Patient with Eye Development Defects.
AB  - BACKGROUND: MSX2 mutations are a very rare cause of craniosynostosis. Gain-of
      function mutations may lead to the Boston-type craniosynostosis with limb defects
      and refraction errors, whereas loss-of-function mutations causes primary osseous
      defects such as enlarged parietal foramina. MATERIALS AND METHODS: Herein we
      report the case of a child with bicoronal synostosis and cutaneous syndactylies,
      who presented iridal and chorioretinal colobomas. Due to the craniofacial
      features that were prominent in the clinical picture, the genes involved in
      craniosynostosis were explored. RESULTS: The patient disclosed an intragenic
      duplication of the entire MSX2 gene whereas no mutation was identified in any
      major genes known to be involved in craniosynostosis. CONCLUSION: This is the
      first report of an eye development defect due to an increase in the MSX2 copy
      number in a human being. The implication of this gene in eye development has
      already been shown in several animal models. Indeed, overexpression of the Msx2
      gene in a mouse model resulted also in optic nerve aplasia and microphthalmia.
      This report expands the phenotypic spectrum of the MSX2 mutations impacting early
      ocular development knowledge.

PMID- 24666291
TI  - Congenital hypothyroidism in Rieger Syndrome.
AB  - Rieger syndrome (RS) is a multiple malformation syndrome characterized by ocular
      manifestations and extraocular defects. Herein, we report a 9-year-old boy who
      exhibited Rieger Syndrome phenotype as well as congenital hypothyroidism which
      may be an underappreciated feature of RS. 

PMID- 24666292
TI  - New pyrano[2,3-c]pyridazine derivatives with antimicrobial activity synthesized
      using piperidine as the organocatalyst.
AB  - A simple and efficient method for the synthesis of highly diverse pyrano[2,3
      c]pyridazines was achieved by a one pot multicomponent reaction using piperidine
      as the organocatalyst. The synthesis of a series of heterocyclic derivatives with
      varying functionality (e.g. thiazine, tetrazole and pyrimidine) incorporating the
      pyrano[2,3-c]pyridazine moiety were achieved via reaction of 2a-e with different
      reagents. The structures of the synthesized derivatives were elucidated by FTIR,
      MS, (1)H and (13)C NMR spectroscopy. A number of the newly synthesized targeted
      compounds 2b-e, 3a-c and 4a-c were evaluated for their in vitro antibacterial
      activity and were compared with chloramphenicol and nystatin as broad spectrum
      reference standard antibiotics. Tests were carried out against Staphylococcus
      aureus (MTCC3160) and Enterococcusi fecalis as Gram-positive bacteria, and
      Escherichia coli (MTCC1652) and Klebsiella pneumonia as Gram-negative bacteria.
      Antifungal potential against Candida albicans, and Aspergillus albicans strains
      were also evaluated. The results revealed that compounds 3a and 3c showed strong
      significant activity relative to the reference against these bacterial and fungal
      strains.

PMID- 24666293
TI  - Ginsenoside F2 possesses anti-obesity activity via binding with PPARgamma and
      inhibiting adipocyte differentiation in the 3T3-L1 cell line.
AB  - Abstract Panax ginseng Meyer has been shown to be effective in mitigating various
      diseases. Protopanaxadiols (PPD) and protopanaxatriols (PPT), which are the main
      constituents of ginseng, have been shown to impact obesity. Therefore, we
      selected several important ginsenosides to perform our docking study and
      determine if they had binding affinity with the peroxisome proliferator activated
      receptor gamma (PPARgamma), which is a major transcription factor in adipocytes.
      Among them, only a few ginsenosides demonstrated binding affinity with PPARgamma.
      Other than ginsenoside F2 rest of them were previously reported by the
      researchers in experimental study in case of obesity cell line 3T3-L1 adipocyte.
      In few recent studies, it was reported that F2 has protective effects on
      malignant brain tumors as well as anti-cancer activity in breast cancer.
      Therefore, we felt it was important to focus on F2 when considering obesity. Our
      study focused on this ginsenoside and analyzed its impact on 3T3-L1 adipocytes.
      Following the molecular interaction studies, further experimental studies were
      carried out and demonstrated that ginsenoside F2 when treated with different
      doses reduces the level of lipid accumulated by the 3T3-L1 cell line during
      adipogenesis. Reverse transcriptase polymerase chain reaction (RT-PCR) and
      quantitative real-time PCR results showed reduction in PPARgamma and perilipin
      gene expression levels compared to that of differentiated adipocytes without any
      treatment. So considering the binding with a major adipocyte transcription factor
      and the performed experiments, we suggest that ginsenoside F2 may reduce obesity
      via the inhibition of adipogenesis in the 3T3-L1 cell line. 

PMID- 24666294
TI  - Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new
      series of sulfonamides incorporating aroylhydrazone-, [1,2,4]triazolo[3,4
      b][1,3,4]thiadiazinyl- or 2-(cyanophenylmethylene)-1,3,4-thiadiazol-3(2H)-yl
      moieties.
AB  - A series of benzenesulfonamides incorporating aroylhydrazone, piperidinyl,
      sulfone, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl- or 2-(cyanophenyl-methylene)
      1,3,4-thiadiazol-3(2H)-yl moieties was investigated as inhibitors of four alpha
      carbonic anhydrases (CAs, EC 4.2.1.1), the human (h) isoforms hCA I, II
      (cytosolic, offtarget enzymes) and hCA IX and XII (transmembrane, tumor
      associated isoforms). Low nanomolar activity was observed against hCA II (KIs of
      0.56-17.1 nM) with these sulfonamides, whereas the slow cytosolic isoform hCA I
      was less inhibited by these compounds (KIs of 86.4 nM-32.8 uM). Most of these
      sulfonamides significantly inhibited CA IX, with KIs in the range of 4.5-47.0 nM,
      although some of the derivatives incorporating bulkier bicyclic moieties, as well
      as 2-thienyl fragments, showed a weaker activity against this isoform (KIs in the
      range 50.1-553 nM). All the investigated compounds also inhibited CA XII with KIs
      in the range 0.85-376 nM. The best inhibitors were those incorporating bulky
      [1,2,4]triazolo[3,4-b][1,3,4]thiadiazinyl moieties and 1,3,4-thiadiazol-3(2H)-yl
      groups.

PMID- 24666295
TI  - New barbiturates and thiobarbiturates as potential enzyme inhibitors.
AB  - A series of 27 new barbiturates and thiobarbiturates have been synthesized by a
      convenient multi-component reaction in overall excellent yields (87-96%). All the
      synthesized compounds were characterized by 1H, 13C NMR, EIMS and elemental
      analysis (C, H, N and S). Furthermore, all compounds were screened for in vitro
      antioxidant (DPPH radical scavenging), lipoxygenase, chymotrypsin, alpha
      glucosidase and anti-urease activities. Out of the series, 23 in DPPH, 14 in
      lipoxygenase, 2 in chymotrypsin have shown appreciable IC50 values.

PMID- 24666296
TI  - Discovery of butyrylcholinesterase inhibitors among derivatives of
      azaphenothiazines.
AB  - The study presents the discovery of novel butyrylcholinesterase (BuChE)
      inhibitors among derivatives of azaphenothiazines by application of in silico and
      in vitro screening methods. From an in-house library of compounds, 143
      heterocyclic molecules derived from the azaphenothiazine scaffold were chosen for
      virtual screening. Based on results of the docking procedure, 15 compounds were
      identified as exhibiting the best fit for the two screening complexes (ligand -
      AChE and ligand - BuChE). Five compounds displayed moderate AChE and good BuChE
      inhibitory activity at screening concentrations of 10 uM. The IC50 values for
      active BuChE inhibitors were in the 11.8-122.2 nM range. Three of the most active
      inhibitors are tetra- or pentacyclic derivatives of azaphenothiazines with the
      same N-methyl-2-piperidinethyl substituent.

PMID- 24666297
TI  - Design, synthesis and pharmacological evaluation of indolylsulfonamide amines as
      potent and selective 5-HT6 receptor antagonists.
AB  - A series of N'-[3-(indole-1-sulfonyl) aryl]-N,N-dimethyl ethane-1,2-diamines and
      N'-[3-(indole-1-sulfonyl) aryl]-N,N-dimethyl propane-1,3-diamines was designed
      and synthesized as 5-HT6 receptor ligands. These compounds, when screened in a
      functional reporter gene-based assay, displayed potent antagonistic activity with
      Kb values in the range of 1.8-60 nM. The lead compound 9y has shown good ADME
      surrogate properties, acceptable pharmacokinetic profile and is active in animal
      models of cognition like novel object recognition test and Morris water maze. It
      was selected for detailed profiling.

PMID- 24666298
TI  - Antioxidant, anti-inflammatory potential and chemical constituents of Origanum
      dubium Boiss., growing wild in Cyprus.
AB  - Origanum dubium Boiss. is a flavouring herb widely used in Cyprus. In this study,
      both lipophilic and polar extracts of the aerial parts of O. dubium were
      investigated for their chemical contents and their antioxidant potential.
      Overall, 20 constituents were isolated and identified, belonging mainly to three
      significant classes of compounds: terpenes, phenolic derivatives, such as
      hydroquinone glycosides and flavonoids and alicyclic derivatives. None of them
      was previously reported as constituent of O. dubium The inhibitory potencies of
      all total extracts and the isolated compounds on lipid peroxidation and their
      interaction with 1,1-diphenyl-picrylhydrazyl (DPPH) activity is discussed. The
      polar extract showed strong interaction with DPPH stable radical and significant
      inhibition of lipoxygenase and lipid peroxidation.

PMID- 24666299
TI  - Investigation of arenesulfonyl-2-imidazolidinones as potent carbonic anhydrase
      inhibitors.
AB  - A series of arenesulfonyl-2-imidazolidinones incorporating methyl, isopropyl,
      methoxy, halogen and phenyl moieties were prepared and tested as possible
      inhibitors of two members of the pH regulatory enzyme family, carbonic anhydrase
      (CA; EC 4.2.1.1). The inhibitory potencies of the compounds against human
      isoforms hCA I and hCA II were analyzed by an esterase assay with 4-nitrophenyl
      acetate as substrate, and the inhibition constants (KI) were calculated. Most
      compounds investigated here exhibited micromolar inhibition constants against the
      two isoenzymes. KI values were in the range of 10.2-40.6 MUM for hCA I and of
      13.1-31.4 MUM for hCA II, respectively. Most of the imidazolidinones showed
      interesting CA inhibitory efficacy, some of them having comparable affinity (for
      hCA I) as the clinically used sulfonamide acetazolamide (AZA), but their efficacy
      against hCA II was much lower compared to AZA.

PMID- 24666300
TI  - Cholinesterase inhibitory triterpenoids from the bark of Garcinia hombroniana.
AB  - Context: Garcinia hombroniana Pierre, known as manggis hutan in Malaysia is a
      rich source of xanthones and benzophenones. OBJECTIVES: This study was aimed to
      isolate and characterize potential cholinesterase inhibitors from the extracts of
      G. hombroniana bark and investigate their interactions with the enzymes.
      MATERIALS AND METHODS: The dichloromethane extract afforded five triterpenoids
      which were characterized by NMR and mass spectral techniques. Cholinesterase
      inhibitory assay and molecular docking were performed to get insight of the
      inhibitory activity and molecular interactions of the compounds. The compounds
      were also tested for their antioxidant capacity. RESULTS: The isolated
      triterpenoids were identified as: 2beta-hydroxy-3alpha-O-caffeoyltaraxar-14-en-28
      oic acid (1), taraxerol (2), taraxerone (3), betulin (4) and betulinic acid (5).
      Compound 1 was the most active dual inhibitor of both AChE and BChE. Compound 1
      also showed good antioxidant activities. CONCLUSION: Compound 1 had dual and
      moderate inhibitory activity on AChE and BChE worthy for further investigations.

PMID- 24666301
TI  - Synthesis and evaluation of new thiadiazole derivatives as potential inhibitors
      of human carbonic anhydrase isozymes (hCA-I and hCA-II).
AB  - 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone
      derivatives (3a--s) were designed as human carbonic anhydrase isozymes (hCA-I and
      hCA-II) inhibitors and synthesized. hCA-I and hCA-II were purified from
      erythrocyte cells by the affinity chromatography. The inhibitory effects of 18
      newly synthesized acetophenones on hydratase activity of these isoenzymes were
      studied in vitro. The average IC50 values of the new compounds for hydratase
      activity ranged from 0.033 to 0.14 MUM for hCA-I and from 0.030 to 0.11 MUM for
      hCA-II. Among the newly synthesized compounds, 2-[[5-(2,4-dichlorophenylamino)
      1,3,4-thiadiazol-2-yl]thio]-4'-bromoacetophenone (3n) can be considered as a
      promising hCA-II inhibitor owing to its selective and potent inhibitory effect on
      hCA-II.

PMID- 24666302
TI  - Computational investigation of the selectivity of salen and tetrahydrosalen
      compounds towards the tumor-associated hCA XII isozyme.
AB  - In previous work, 14 salen and tetrahydrosalen compounds have been synthesized
      and tested in enzyme inhibition assays against cytosolic human carbonic anhydrase
      isozymes I and II (hCA I and II) and tumor-associated isozymes IX and XII (hCA IX
      and XII). These compounds show selectivity against hCA XII over hCA I, II and IX.
      In this study, molecular modeling and docking studies were applied to understand
      this preference of the compounds for hCA XII. Most likely, the compounds can
      displace the zinc-bound water molecule of hCA XII to form a direct interaction
      with the Zn(2+) ion. In the other isozymes, the compounds might not be able to
      displace the water molecule nor are they expected to interact with the Zn(2+)
      ion.

PMID- 24666304
TI  - Synthesis and biological activity of novel thiourea derivatives as carbonic
      anhydrase inhibitors.
AB  - A new series of chiral thiourea derivatives (5a-5c) and thiourea containing
      benzimidazole moieties (9b-9e) were synthesized from different amino acids (l
      valine, l-isoleucine, l-methionine, l-phenylalanine, and d-phenylglycine). The
      compounds were characterized and tested against the two most studied members of
      the pH regulatory enzyme family, carbonic anhydrase (CA, EC 4.2.1.1). KI values
      of the novel compounds were measured in the range of 3.4-73.6 MUM for hCA I
      isozyme and 8.7-1.44.2 MUM for hCA II isozyme, respectively. Phenol was also
      tested as standard in order to understand the structure activity relationship and
      the clinically used sulfonamide acetazolamide was tested for comparison reasons.
      All of the compounds exhibited competitive inhibition with 4-nitrophenylacetate
      as substrate.

PMID- 24666303
TI  - 2-Chloro-1,4-naphthoquinone derivative of quercetin as an inhibitor of aldose
      reductase and anti-inflammatory agent.
AB  - The ability of flavonoids to affect multiple key pathways of glucose toxicity, as
      well as to attenuate inflammation has been well documented. In this study, the
      inhibition of rat lens aldose reductase by 3,7-di-hydroxy-2-[4-(2-chloro-1,4
      naphthoquinone-3-yloxy)-3-hydroxy-phenyl]-5-hydroxy-chromen-4-one (compound 1),
      was studied in greater detail in comparison with the parent quercetin (compound
      2). The inhibition activity of 1, characterized by IC50 in low micromolar range,
      surpassed that of 2. Selectivity in relation to the closely related rat kidney
      aldehyde reductase was evaluated. At organ level in isolated rat lenses incubated
      in the presence of high glucose, compound 1 significantly inhibited accumulation
      of sorbitol in a concentration-dependent manner, which indicated that 1 was
      readily taken up by the eye lens cells and interfered with cytosolic aldose
      reductase. In addition, compound 1 provided macroscopic protection of colonic
      mucosa in experimental colitis in rats. At pharmacologically active
      concentrations, compound 1 and one of its potential metabolite 2-chloro-3-hydroxy
      [1,4]-naphthoquinone (compound 3) did not affect osmotic fragility of red blood
      cells.

PMID- 24666305
TI  - Carbonic anhydrase inhibition by 1-aroyl-3-(4-aminosulfonylphenyl)thioureas.
AB  - A series of 1-aroyl-3-(4-aminosulfonylphenyl)thioureas containing free
      sulfonamide group has been evaluated for their ability to inhibit bovine carbonic
      anhydrase II (bCA, EC 4.2.1.1). All compounds in the series were able to inhibit
      bCA II, the most active inhibitor had IC50 value of 0.26 +/- 0.01 uM. Molecular
      docking studies and detailed structure-activity relationship studies were carried
      out. The absorption, distribution, metabolism, excretion (ADME) properties, as a
      predictor of oral absorption, were computationally calculated and compared with
      the clinically used drug acetazolamide.

PMID- 24666306
TI  - Design, synthesis, characterization and in vitro and in vivo anti-inflammatory
      evaluation of novel pyrazole-based chalcones.
AB  - Abstract A series of novel pyrazole-based chalcones have been designed,
      synthesized from 1-methyl-5-(2,4,6-trimethoxyphenyl)-1H-pyrazole (6). The
      structures of regioisomers 6 and 7 were determined by 2D (1)H-(1)H COSY, (1)H
      (13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds were
      tested for their inhibitory activity against COX-1 and COX-2 using an in vitro
      cyclooxygenase (COX) inhibition assay. Moreover, they were investigated in vivo
      for their anti-inflammatory activities using carrageenan-induced rat paw edema
      model for acute inflammation and cotton pellet-induced granuloma model for
      chronic inflammation. All the synthesized compounds showed potential to
      demonstrate anti-inflammatory activities, of particular interest compounds 10i,
      10e, 10f, and 10h were found to be potent anti-inflammatory agents. 

PMID- 24666307
TI  - Recent advances in structure of progestins and their binding to progesterone
      receptors.
AB  - The role of progesterone in women's cancers as well as the knowledge of the
      progesterone receptor (PR) structure has prompted the design of different
      therapies. The aim of this review is to describe the basic structure of PR
      agonists and antagonists as well as the recent treatments for illness associated
      with the progesterone receptor. The rational design for potent and effective
      drugs for the treatment of female cancer must consider the structural changes of
      the androgen and progestogen skeleton which are an indicator of their activity as
      progestins or antiprogestins. The presence of a hydroxyl group at C-17 in the
      progesterone skeleton brings about a loss of progestational activity whereas
      acetylation induces a progestational effect. The incorporation of an ethynyl
      functional group to the testosterone framework results in a loss of androgenic
      activity with a concomitant enhancement of the progestational effect. On the
      other hand, an ester function at C-3 of dehydroepiandrosterone skeleton induces
      partial antagonism to the PR.

PMID- 24666308
TI  - Synthesis and potent antistaphylococcal activity of some new 2-[4-(3,4
      dimethoxyphenoxy)phenyl]-1,N-disubstituted-1H-benzimidazole-5-carboxamidines.
AB  - A series of new 2-[4-(3,4-dimethoxyphenoxy)phenyl]-1,N-disubstituted-1H
      benzimidazole-5-carboxamidines (23-33) have been synthesized and evaluated for
      their potential antistaphylococcal activity. Cytotoxic effects of the compounds
      were investigated by the neutral red uptake (NRU) cytotoxicity test. Most of the
      compounds exhibited good MICs values against Staphylococcus aureus and
      methicillin-resistant S. aureus (MRSA). Compound 28 with N
      cyclohexylcarboxamidine group at the 5-position was found to be the most potent
      agent, with the MIC value of 3.12 ug/mL.

PMID- 24666309
TI  - Design, synthesis, and antitumor screening of certain novel tetrahydroquinoline
      sulfonamides.
AB  - Sulfonamide containing molecules are of sound biomedical interest. This work
      comprises the synthesis and in vitro antitumor testing of new library of 20 such
      molecules. These compounds were screened for cytotoxic activity against three
      tumor cell lines MCF-7, HeLa, and HepG2 using MTT assay. The yield was low but
      all the target compounds exhibited antiproliferative activity better than the
      standard drug Doxorubicin (CAS-23214-92-8). Seven compounds were more potent and
      four compounds were as active as the standard drug. There were no great
      difference between compounds obtained from dimedone and those obtained from
      cyclohexandione. Also no significant difference found in activity between
      compounds bearing o-amino ethyl ester side chain and compounds bearing o-amino
      amide derivatives. However, compounds bearing o-amino-cyano group, although
      retained considerable activity they were far less active than the preceding two.
      It was clear that monohydroxy aldehyde derivatives were less active compared with
      the di and trihydroxy ones. 

PMID- 24666312
TI  - Diastereoselective hydroxymethylation of cyclic N-tert-butanesulfinylketimines
      using methoxymethanol as formaldehyde source.
AB  - Hydroxymethylation of cyclic tert-butanesulfinylketimine-derived lithium enamides
      with methoxymethanol proceeds with excellent diastereoselectivity (99:1 dr).
      Methoxymethanol is a stable and easy-to-handle source of anhydrous monomeric
      formaldehyde in the reaction with lithium enamides. Cyclic alpha-hydroxymethyl
      ketimines undergo highly diastereoselective reduction to syn- or anti-1,3-amino
      alcohols.

PMID- 24666311
TI  - Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and
      plain 2009-10 seasonal influenza vaccines in rheumatoid arthritis patients on
      biologicals.
AB  - Rheumatoid arthritis (RA) patients under immunosuppressive therapy are
      particularly susceptible to infections, mainly of the respiratory tract, thus
      vaccination may represent a strategy to reduce their incidence in this vulnerable
      population. In the 2009-10 influenza season, the safety and immunogenicity of co
      administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza
      vaccines were evaluated in this study in 30 RA patients under therapy with anti
      tumour necrosis factor (TNF)-alpha agents or Abatacept and in 13 healthy controls
      (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1
      (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a
      significant increase in total mild side effects in patients versus HC were
      observed. Both influenza vaccines fulfilled the three criteria of the Committee
      for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral
      strain in patients and HC was, respectively, 68 versus 45 for H1
      A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for
      B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in
      activated interferon (IFN)-gamma-, TNF-alpha- or interleukin (IL)-17A-secreting T
      cells at T1 compared to T0, followed by a reduction at T2 in both patients and
      HC, was registered. In conclusion, simultaneous administration of adjuvanted
      pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly
      immunogenic. The largely overlapping results between patients and HC, in terms of
      antibody response and cytokine-producing T cells, may represent further evidence
      for vaccine safety and immunogenicity in RA patients on biologicals. 

PMID- 24666313
TI  - Spondylocostal dysostosis with tetralogy of Fallot and herniation of the spleen
      through the diaphragm.
AB  - Spondylocostal dysostosis (SCD) is a very rare syndrome characterized by
      vertebral malformation and rib deformity. Some of the patients with SCD have
      other birth defects in the central nervous system, the genitourinary tract,
      diaphragm or heart and so forth. There have been reported SCD with complex
      congenital heart disease, such as pulmonary atresia, double outlet right
      ventricle, and d-transposition of great arteries. However, there have been no
      reported SCD patients with confirmed tetralogy of Fallot (TOF). Here, a patient
      with SCD having a very rare combination of rib defects on the right side and left
      sided scoliosis, tetralogy of Fallot, and diaphragmatic spleen herniation, which
      had not been reported before, was described. 

PMID- 24666314
TI  - Effects of inhalational anaesthetics in experimental allergic asthma.
AB  - We evaluated whether isoflurane, halothane and sevoflurane attenuate the
      inflammatory response and improve lung morphofunction in experimental asthma.
      Fifty-six BALB/c mice were sensitised and challenged with ovalbumin and
      anaesthetised with isoflurane, halothane, sevoflurane or pentobarbital sodium for
      one hour. Lung mechanics and histology were evaluated. Gene expression of pro
      inflammatory (tumour necrosis factor-alpha), pro-fibrogenic (transforming growth
      factor-beta) and pro-angiogenic (vascular endothelial growth factor) mediators,
      as well as oxidative process modulators, were analysed. These modulators included
      nuclear factor erythroid-2 related factor 2, sirtuin, catalase and glutathione
      peroxidase. Isoflurane, halothane and sevoflurane reduced airway resistance,
      static lung elastance and atelectasis when compared with pentobarbital sodium.
      Sevoflurane minimised bronchoconstriction and cell infiltration, and decreased
      tumour necrosis factor-alpha, transforming growth factor-beta, vascular
      endothelial growth factor, sirtuin, catalase and glutathione peroxidase, while
      increasing nuclear factor erythroid-2-related factor 2 expression. Sevoflurane
      down-regulated inflammatory, fibrogenic and angiogenic mediators, and modulated
      oxidant-antioxidant imbalance, improving lung function in this model of asthma.

PMID- 24666315
TI  - Use of the low-dose buprenorphine patch: author commentary.

PMID- 24666316
TI  - Stereospecific Ni-catalyzed cross-coupling of potassium alkenyltrifluoroborates
      with alkyl halides.
AB  - A general method for the alkenylation of alkyl electrophiles using nearly
      stoichiometric amounts of the air- and moisture-stable potassium
      organotrifluoroborates has been developed. Various functional groups were
      tolerated on both the nucleophilic and electrophilic partner. Reactions of highly
      substituted E- and Z-alkenyltrifluoroborates, as well as vinyl- and
      propenyltrifluoroborates, were successful, and no loss of stereochemistry or
      regiochemistry was observed. 

PMID- 24666317
TI  - Paediatric anaplastic large cell lymphoma with leukaemic presentation in
      children: a report of nine French cases.
AB  - This study aimed to describe the clinical features and outcome of anaplastic
      large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267
      patients included in the French paediatric ALCL database between 1989 and 2012,
      nine (3%) were described as having cytologically detectable circulating tumour
      cells. Clinical features combined fever (8/9), nodal and extra-nodal disease
      (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of
      hyperleucocytosis ranged from 30 to 120 * 10(9) /l, with 12-90% of tumour cells.
      Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody
      immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3
      positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only
      four patients achieved a complete remission with first-line therapy and 3/4
      relapsed. Four patients are alive with a median follow-up of 31 months, two of
      them after allogeneic haematopoietic stem cell transplantation (HSCT), and five
      patients died, two of them of disease. In conclusion, ALCL with leukaemic
      presentation is very unusual and should be considered as high-risk lymphoma
      requiring new therapeutic strategies. The respective role of new agents and
      allogeneic HSCT in first complete remission still has to be assessed. 

PMID- 24666318
TI  - A novel brominated triazine-based flame retardant (TTBP-TAZ) in plastic consumer
      products and indoor dust.
AB  - The presence of a novel brominated flame retardant named 2,4,6-tris(2,4,6
      tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) is reported for the first time in
      plastic parts of consumer products and indoor dust samples. TTBP-TAZ was
      identified by untargeted screening and can be a replacement of the banned
      polybrominated diphenyl ethers. Analysis techniques based on ambient mass
      spectrometry and on liquid chromatography with atmospheric pressure chemical
      ionization combined with high resolution time-of-flight mass spectrometry were
      developed for the screening, detection and quantification of this low volatility
      and high molecular weight compound. TTBP-TAZ was present in 8 of 13 plastic parts
      of consumer products (from mainly electric and electronic equipment acquired in
      2012) at estimated concentrations of 0.01-1.9% by weight of the product (%, w/w).
      It was not present in any of the older 13 plastic samples that were collected in
      a recycling park (manufacture date before 2006), this suggests a recent use of
      TTBP-TAZ. It was also found in 9 of 17 house dust samples in the range of 160
      22150 ng g(-1), with the highest levels being found in samples collected on
      electronic and electrical equipment. These preliminary results highlight the need
      for further research on TTBP-TAZ and the potential of using alternative analysis
      methods for the identification of new flame retardants. 

PMID- 24666320
TI  - Smoothly tunable surface properties of aluminum oxide core-shell nanoparticles by
      a mixed-ligand approach.
AB  - We present a facile solution-based procedure for tailoring the surface properties
      of aluminum oxide nanoparticles (AlOx-NPs) by the formation of tunable core-shell
      systems with self-assembled monolayers. By employing chained molecules with a
      phosphonic acid anchor group and either hydrophobic or hydrophilic chains the
      surface properties of the nanoparticles change dramatically. So, the solubility
      can be tuned orthogonal from trifluorotoluene (CF3-C6H5) for hydrophobic shell to
      water (H2O) for hydrophilic functionalization respectively. Spray coated films of
      those functionalized nanoparticles exhibited superhydrophobic or superhydrophilic
      properties. The surface properties can be tuned smoothly by the formation of a
      mixed ligand monolayer from corresponding stoichiometric mixtures of the ligands.
      The core-shell nanoparticles were investigated by means of thermogravimetric
      analysis, TGA; Fourier transform infrared spectroscopy, FTIR; and static contact
      angle goniometry, SCA. The effect of different dipole moments of the SAM
      molecules in mixed shell nanoparticles to their stability in dispersions was
      studied by zeta potential measurements. 

PMID- 24666319
TI  - Adventitious root formation in tree species: involvement of transcription
      factors.
AB  - Adventitious rooting is an essential step in the vegetative propagation of
      economically important horticultural and woody species. Populus has emerged as an
      experimental model for studying processes that are important in tree growth and
      development. It is highly useful for molecular genetic analysis of adventitious
      roots in trees. In this short review, we will highlight the recent progress made
      in the identification of transcription factors involved in the control of
      adventitious rooting in woody species. Their regulation will be discussed. 

PMID- 24666321
TI  - Infrared photodissociation spectroscopy of microhydrated nitrate-nitric acid
      clusters NO3(-)(HNO3)(m)(H2O)(n).
AB  - Infrared multiple photon dissociation (IRMPD) spectra of NO3(-)(HNO3)m(H2O)n(H2)z
      with m = 1-3, up to n = 8 and z >= 1, are measured in the fingerprint region (550
      1880 cm(-1)), directly probing the NO-stretching modes, as well as bending and
      other lower frequency modes. The assignment of the spectra is aided by electronic
      structure calculations. The IRMPD spectrum of the m = 1, n = 0 cluster is
      distinctly different from all the other measured spectra as a result of strong
      hydrogen bonding, leading to an equally shared proton in between two nitrate
      moieties (O2NO(-)...H(+)...ONO2(-)). It exhibits a strong absorption at 877 cm(
      1) and lacks the characteristic NO2-antisymmetric stretching/NOH-bending mode
      absorption close to 1650 cm(-1). Addition of at least one more nitric acid
      molecule or two more water molecules weakens the hydrogen bond network, breaking
      the symmetry of this arrangement and leading to localization of the proton near
      one of the nitrate cores, effectively forming HNO3 hydrogen-bonded to NO3(-). Not
      all IR active modes are observed in the IRMPD spectra of the bare nitrate-nitric
      acid clusters. Addition of a water or a hydrogen molecule lowers the dissociation
      limit of the complexes and relaxes (H2O) or lifts (H2) this IRMPD transparency. 

PMID- 24666323
TI  - Microwave-assisted chemistry: synthetic applications for rapid assembly of
      nanomaterials and organics.
AB  - The magic of microwave (MW) heating technique, termed the Bunsen burner of the
      21st century, has emerged as a valuable alternative in the synthesis of organic
      compounds, polymers, inorganic materials, and nanomaterials. Important
      innovations in MW-assisted chemistry now enable chemists to prepare catalytic
      materials or nanomaterials and desired organic molecules, selectively, in almost
      quantitative yields and with greater precision than using conventional heating.
      By controlling the specific MW parameters (temperature, pressure, and ramping of
      temperature) and choice of solvents, researchers can now move into the next
      generation of advanced nanomaterial design and development. Microwave-assisted
      chemical reactions are now well-established practices in the laboratory setting
      although some controversy lingers as to how MW irradiation is able to enhance or
      influence the outcome of chemical reactions. Much of the discussion has focused
      on whether the observed effects can, in all instances, be rationalized by purely
      thermal Arrhenius-based phenomena (thermal microwave effects), that is, the
      importance of the rapid heating and high bulk reaction temperatures that are
      achievable using MW dielectric heating in sealed reaction vessels, or whether
      these observations can be explained by so-called "nonthermal" or "specific
      microwave" effects. In recent years, innovative and significant advances have
      occurred in MW hardware development to help delineate MW effects, especially the
      use of silicon carbide (SiC) reaction vessels and the accurate measurement of
      temperature using fiber optic (FO) temperature probes. SiC reactors appear to be
      good alternatives to MW transparent borosilicate glass, because of their high
      microwave absorptivity, and as such they serve as valuable tools to demystify the
      claimed magical MW effects. This enables one to evaluate the influence of the
      electromagnetic field on the specific chemical reactions, under truly identical
      conventional heating conditions, wherein temperature is measured accurately by
      fiber optic (FO) probe. This Account describes the current status of MW-assisted
      synthesis highlighting the introduction of various prototypes of equipment,
      classes of organic reactions pursued using nanomaterials, and the synthesis of
      unique and multifunctional nanomaterials; the ensuing nanomaterials possess zero
      dimensional to three-dimensional shapes, such as spherical, hexagonal,
      nanoprisms, star shapes, and nanorods. The synthesis of well-defined
      nanomaterials and nanocatalysts is an integral part of nanotechnology and
      catalysis science, because it is imperative to control their size, shape, and
      compositional engineering for unique deployment in the field of nanocatalysis and
      organic synthesis. MW-assisted methods have been employed for the convenient and
      reproducible synthesis of well-defined noble and transition core-shell metallic
      nanoparticles with tunable shell thicknesses. Some of the distinctive attributes
      of MW-selective heating in the synthesis and applications of magnetic
      nanocatalysts in organic synthesis under benign reaction conditions are
      highlighted. Sustainable nanomaterials and their applications in benign media are
      an ideal blend for the development of greener methodologies in organic synthesis;
      MW heating provides superb value to the overall sustainable process development
      via process intensification including the flow systems.

PMID- 24666322
TI  - HIV-1 protein Tat produces biphasic changes in NMDA-evoked increases in
      intracellular Ca2+ concentration via activation of Src kinase and nitric oxide
      signaling pathways.
AB  - HIV-associated neurocognitive disorders afflict about half of HIV-infected
      patients. HIV-infected cells shed viral proteins, such as the transactivator of
      transcription (Tat), which can cause neurotoxicity by over activation of NMDA
      receptors. Here, we show that Tat causes a time-dependent, biphasic change in
      NMDA-evoked increases in intracellular Ca(2+) concentration ([Ca(2+)]i). NMDA
      evoked responses were potentiated following 2-h exposure to Tat (50 ng/mL). Tat
      induced potentiation of NMDA-evoked increases in [Ca(2+)]i peaked by 8 h and then
      adapted by gradually reversing to baseline by 24 h and eventually dropping below
      control by 48 h. Tat-induced potentiation of NMDA-evoked responses was blocked by
      inhibition of lipoprotein receptor-related protein (LRP) or Src tyrosine kinase.
      Potentiation was unaffected by inhibition of nitric oxide synthase (NOS).
      However, NOS activity was required for adaptation. Adaptation was also prevented
      by inhibition of soluble guanylate cyclase (sGC) and cyclic guanosine
      monophosphate-dependent protein kinase G (PKG). Together, these findings indicate
      that Tat potentiates NMDA-evoked increases in [Ca(2+)]i via LRP-dependent
      activation of Src and that this potentiation adapts via activation of the
      NOS/sGC/PKG pathway. Adaptation may protect neurons from excessive Ca(2+) influx
      and could reveal targets for the treatment of HIV-associated neurocognitive
      disorders. HIV-associated neurocognitive disorders (HAND) afflict about half of
      HIV-infected patients. HIV-infected cells shed viral proteins, such as the
      transactivator of transcription (Tat), which can cause neurotoxicity by over
      activation of NMDA receptors (NMDARs). We show that HIV-1 Tat evoked biphasic
      changes in NMDA-evoked [Ca(2+) ]i responses. Initially, Tat potentiated NMDA
      evoked responses following LRP-mediated activation of Src kinase. Subsequently,
      Tat-induced NMDAR potentiation adapted by activation of a NOS/sGC/PKG pathway
      that attenuated NMDA-evoked increases in [Ca(2+)]i . Adaptation may be a novel
      neuroprotective mechanism to prevent excessive Ca(2+) influx. Solid and dashed
      arrows represent direct and potentially indirect connections, respectively.

PMID- 24666324
TI  - Effect of the UK's revised paracetamol poisoning management guidelines on
      admissions, adverse reactions and costs of treatment.
AB  - AIMS: In September 2012 the UK's Commission on Human Medicines (CHM) recommended
      changes in the management of paracetamol poisoning: use of a single '100 mg l(-1)
      ' nomogram treatment line, ceasing risk assessment, treating all
      staggered/uncertain ingestions and increasing the duration of the initial
      acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this
      on presentation, admission, treatment, adverse reactions and costs of paracetamol
      poisoning. METHODS: Data were prospectively collected from adult patients
      presenting to three large UK hospitals from 3 September 2011 to 3 September 2013
      (year before and after change). Infusion duration effect on vomiting and
      anaphylactoid reactions was examined in one centre. A cost analysis from an NHS
      perspective was performed for 90 000 patients/annum with paracetamol overdose.
      RESULTS: There were increases in the numbers presenting to hospital (before 1703,
      after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703
      [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and
      proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95%
      CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the
      proportion of treated patients developing adverse reactions (15 min 87/323
      [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI -4.9, 7.5], P = 0.682).
      Across the UK the estimated cost impact is L8.3 million (6.4 million-10.2
      million) annually, with a cost-per-life saved of L17.4 million (13.4 million-21.5
      million). CONCLUSIONS: The changes introduced by the CHM in September 2012 have
      increased the numbers of patients admitted to hospital and treated with
      acetylcysteine without reducing adverse reactions. A safety and cost-benefit
      review of the CHM guidance is warranted, including novel treatment protocols and
      biomarkers in the assessment of poisoning.

PMID- 24666326
TI  - Health promotion strategies for families with adolescents orphaned by HIV and
      AIDS.
AB  - PURPOSE: This paper aims to explore and describe health promotion strategies for
      adolescents orphaned by human immunodeficiency virus (HIV) and acquired
      immunodeficiency syndrome (AIDS), as well as the evaluation thereof. INTRODUCTION
      AND BACKGROUND: Among the Sub-Saharan countries, such as Swaziland, Botswana and
      Lesotho, South Africa is rated as fourth in the list of countries with the
      highest number of people living with HIV and AIDS. METHOD: The study employed
      phenomenological qualitative design. The population consisted of the purposively
      selected health promoters working in the Hammanskraal region, directly and
      indirectly involved with families with adolescents orphaned by HIV and AIDS.
      Following the focus group interviews, data were analysed using the seven steps of
      Colaizzi. RESULTS: Four categories and eight subcategories were concluded as the
      strategies for adolescents orphaned by HIV and AIDS as well as the evaluation
      thereof. The main categories identified were: the door-to-door outcome, workshop
      outputs, statistical data and community projects. DISCUSSION: It is evident that
      the health promotion strategies informed by the four themes will be implemented.
      The outcomes may raise an awareness in the community, support families and
      provide statistics on the impact of HIV and AIDS on families. STUDY LIMITATIONS:
      The study was limited to one subdistrict and to health promoters in a rural area,
      therefore the results cannot be generalized to all other subdistricts including
      health promoters, especially those in urban areas. CONCLUSION: The successful
      evaluation programme will pin out the strong points and challenges while
      assisting in improving the quality of work provided in the communities.
      IMPLICATION FOR NURSING AND HEALTH POLICY: Continuing professional and practice
      development are required to maintain the standard of health care in South Africa.
      Therefore the policymakers need to include relevant information regarding health
      promotion strategies in reducing the statistics of people living with HIV and
      AIDS.

PMID- 24666325
TI  - Caffeine stabilizes Cdc25 independently of Rad3 in Schizosaccharomyces pombe
      contributing to checkpoint override.
AB  - Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle
      progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in
      a Rad3-dependent manner. Caffeine is believed to override activation of the
      replication and DNA damage checkpoints by inhibiting Rad3-related proteins in
      both Schizosaccharomyces pombe and mammalian cells. In this study, we have
      investigated the impact of caffeine on Cdc25 stability, cell cycle progression
      and checkpoint override. Caffeine induced Cdc25 accumulation in S. pombe
      independently of Rad3. Caffeine delayed cell cycle progression under normal
      conditions but advanced mitosis in cells treated with replication inhibitors and
      DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle
      progression even in the presence of hydroxyurea or phleomycin. Caffeine induces
      Cdc25 accumulation in S. pombe by suppressing its degradation independently of
      Rad3. The induction of Cdc25 accumulation was not associated with accelerated
      progression through mitosis, but rather with delayed progression through
      cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability
      to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell
      cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest
      that caffeine overrides checkpoint enforcement by inducing the inappropriate
      nuclear localization of Cdc25. 

PMID- 24666327
TI  - Axinelline A, a new COX-2 inhibitor from Streptomyces axinellae SCSIO02208.
AB  - Axinelline A, a new cyclooxygenase-2 (COX-2) inhibitor, was isolated from
      Streptomyces axinellae SCSIO02208. The structures of compounds 1-9 were
      determined by analysing the NMR and MS data. The absolute configuration of 1 was
      determined by using optical rotation and comparing with the reported data.
      Compound 1 exhibited COX-2 inhibitory activity, the IC50 value being 2.8 MUM.

PMID- 24666329
TI  - A polymorphism in XKR4 is significantly associated with serum prolactin
      concentrations in beef cows grazing tall fescue.
AB  - Fescue toxicosis is a common syndrome of poor growth and reproductive performance
      of beef cattle grazing endophyte-infected tall fescue infected with Lolium
      arundinaceum Schreb. Together with decreased feed intake, decreased growth rates
      and tissue necrosis due to vasoconstriction, depressed circulating serum
      prolactin concentrations are typically observed in cattle afflicted with fescue
      toxicosis. Polymorphisms within the XK, Kell blood group complex subunit-related
      family, member 4 (XKR4) gene located on BTA14 have been previously reported to be
      associated with rump fat thickness, residual feed intake, average daily feed
      intake and average daily gain in cattle. Associations also have been reported
      between XKR4 genotype and effectiveness of the dopamine antagonist iloperidone as
      a treatment of schizophrenia in humans. Domperidone, a related dopamine
      antagonist, mediates effects of fescue toxicosis on livestock, including
      restoring depressed concentrations of prolactin. A mixed-breed population of 592
      beef cattle grazing endophyte-infected tall fescue was used to examine the
      association between XKR4 genotype and circulating prolactin concentrations. The
      SNP rs42646708 was significantly (P = 0.0002) associated with serum prolactin
      concentrations and explained 2.45% of the phenotypic variation. Effect of
      genotype at the SNP was tested across five breeds, with significant associations
      within both Angus (P = 0.0275) and Simmental (P = 0.0224) breeds. These results
      suggest XKR4 may play a role in mediating the negative effects of fescue
      toxicosis, and polymorphisms within this gene may be useful markers for selection
      for genetic resistance to the debilitating effects of endophyte-infected tall
      fescue.

PMID- 24666328
TI  - Molecular characterization of turkey enteric reovirus S3 gene.
AB  - The molecular diversity in S3 gene sequences of turkey reovirus (TRV) was
      determined in poult enteritis syndrome (PES)-affected and apparently healthy
      turkey poults. Twenty-nine TRV-positive samples (15 from PES-affected flocks and
      14 from apparently healthy flocks) were tested using self-designed primers for
      the S3 gene. Phylogenetic analysis revealed that the TRV S3 sequences of this
      study clustered in clade III and formed two different groups in this clade. The
      avian reoviruses from duck and goose formed clade I and those from chickens
      formed clade II. The clade III TRV sequences had a nucleotide percent identity of
      88.9 to 100% among themselves but only of 59.5 to 63.5% and 69.2 to 72.6% with
      clades I and II, respectively. More amino acid substitutions were present in TRVs
      from PES-affected flocks than in those from apparently healthy flocks using ATCC
      VR-818 (AY444912) as a benchmark. All TRVs of this study showed substitutions at
      positions 244 and 285. The impact of these changes on the virulence of the virus,
      if any, needs to be studied. 

PMID- 24666330
TI  - Pyrimidine-fused heterocyclic frameworks based on an N4-arylcytosine scaffold:
      synthesis, characterization, and PNA oligomerization of the fluorescent cytosine
      analogue 5,6-benzopC.
AB  - A synthesis of an intrinsically fluorescent cytosine analogue 5,6-benzopC has
      been developed utilizing the reductive Ni-mediated cyclization of an N4-aryl,N4
      (Boc)cytosine intermediate as a key step. 5,6-BenzopC was found to possess
      interesting fluorescence properties (Phi = 0.79, EtOH; Stoke's shift 113 nm).
      Peptide nucleic acid (PNA) oligomerization of the 5,6-benzopC monomer was carried
      out, followed by hybridization studies with complementary deoxyribonucleic acid
      (DNA) and ribonucleic acid (RNA) which showed the modification to be well
      tolerated in the sequence contexts examined. Initial attempts to synthesize the
      heterocyclic skeleton present in 5,6-benzopC resulted in the discovery of routes
      to the pyrimido[1,6-a]benzimidazole, pyrimido[1,6-a]quinazoline, and pyrimido[1,6
      a]benzo[b]6-bora-1,3-diazine heterocyclic frameworks.

PMID- 24666331
TI  - Measuring the human body's microclimate using a thermal manikin.
AB  - The human body is surrounded by a microclimate, which results from its convective
      release of heat. In this study, the air temperature and flow velocity of this
      microclimate were measured in a climate chamber at various room temperatures,
      using a thermal manikin simulating the heat release of the human being. Different
      techniques (Particle Streak Tracking, thermography, anemometry, and thermistors)
      were used for measurement and visualization. The manikin surface temperature was
      adjusted to the particular indoor climate based on simulations with a
      thermoregulation model (UCBerkeley Thermal Comfort Model). We found that
      generally, the microclimate is thinner at the lower part of the torso, but
      expands going up. At the head, there is a relatively thick thermal layer, which
      results in an ascending plume above the head. However, the microclimate shape
      strongly depends not only on the body segment, but also on boundary conditions:
      The higher the temperature difference between the surface temperature of the
      manikin and the air temperature, the faster the airflow in the microclimate.
      Finally, convective heat transfer coefficients strongly increase with falling
      room temperature, while radiative heat transfer coefficients decrease. The type
      of body segment strongly influences the convective heat transfer coefficient,
      while only minimally influencing the radiative heat transfer coefficient.
      PRACTICAL IMPLICATIONS: The findings of this study generate a better
      understanding of the human body's microclimate, which is important in fields such
      as thermal comfort, HVAC, or indoor air quality. Additionally, the measurements
      can be used by CFD users for the validation of their simulations.

PMID- 24666332
TI  - LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 
      2014).
AB  - INTRODUCTION: Integration of the viral genome into the host cell chromatin is a
      central step in the replication cycle of the HIV. Blocking the viral integrase
      (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced
      by the recent clinical approval of three IN strand transfer inhibitors. Viral
      resistance and cross-resistance among these inhibitors, however, warrant the
      search for compounds targeting HIV integration through alternative mechanisms of
      action. AREAS COVERED: The most potent class of allosteric IN inhibitors was
      independently identified at the University of Leuven, Belgium, and at Boehringer
      Ingelheim, Canada. These compounds, coined LEDGINs (after the lens epithelium
      derived growth factor/p75 cofactor binding pocket on IN) or non-catalytic site IN
      inhibitors (NCINIs) by the respective groups, have shown remarkable antiviral
      activity. This review provides a brief introduction to the compound class and
      discusses the recent patent literature (2006 to the present). EXPERT OPINION:
      LEDGINs are still early in development. Trials with clinical candidate BI-224436
      were put on hold despite promising results. Literature, however, reveals that
      almost all major pharmaceutical companies active in the treatment of HIV/AIDS
      have taken a significant interest in this class. As a result, several of these
      inhibitors may soon enter clinical trials.

PMID- 24666333
TI  - Effect of Offset Implant Placement on the Stress Distribution Around a Dental
      Implant: A Three-Dimensional Finite Element Analysis.
AB  - There are some anatomical restrictions in which implants are not possible to be
      inserted in their conventional configuration. Offset placement of implants in
      relation to the prosthetic unit could be a treatment solution. The aim of this
      study was to evaluate the effect of the offset placement of implant-supported
      prosthesis on the stress distribution around a dental implant using 3D finite
      element analysis. 3D finite element models of implant placement in the position
      of a mandibular molar with 4 configurations (0, 0.5, 1, 1.5 mm offset) were
      created in order to investigate resultant stress/strain distribution. A vertical
      load of 100 N was applied on the center of the crown of the models. The least
      stress in peri-implant tissue was found in in-line configuration (0 mm offset).
      Stress concentration in the peri-implant tissue increased by increasing the
      amount of offset placement. Maximum stress concentration in all models was
      detected at the neck of the implant. It can be concluded that the offset
      placement of a single dental implant does not offer biomechanical advantages
      regarding reducing stress concentration over the in-line implant configuration.
      It is suggested that the amount of offset should be as minimum as possible. 

PMID- 24666334
TI  - Impact of genetic deficiencies of P-glycoprotein and breast cancer resistance
      protein on pharmacokinetics of aripiprazole and dehydroaripiprazole.
AB  - 1. We investigated how deficiencies in P-glycoprotein (P-gp) and breast cancer
      resistance protein (BCRP) affect the pharmacokinetics of atypical antipsychotics
      aripiprazole and its active metabolite (dehydroaripiprazole) using normal Friend
      leukemia virus strain B (FVB) mice, BCRP knockout (Bcrp[-/-]) mice, and P-gp and
      BCRP triple knockout (Mdr1a/1b[-/-]Bcrp[-/-]) mice. 2. While plasma
      concentrations of aripiprazole and dehydroaripiprazole after oral administration
      were slightly higher in both Bcrp(-/-) and Mdr1a/1b(-/-)/Bcrp(-/-) mice than in
      normal FVB mice, the difference was not marked. The increase in absolute
      bioavailability (F) compared with normal mice (approximately 1.3-fold increase)
      was comparable between Bcrp(-/-) and Mdr1a/1b(-/-)/Bcrp(-/-) mice. This finding
      suggests that BCRP may be involved in the intestinal absorption of aripiprazole
      in mice, albeit with minimal contribution to absorption at best. 3. In contrast,
      the brain-to-plasma concentration ratio (Kp,brain) for aripiprazole and
      dehydroaripiprazole after oral administration was significantly higher in
      Mdr1a/1b(-/-)/Bcrp(-/-) mice than in normal mice, whereas Bcrp(-/-) mice
      exhibited Kp,brain values similar to those in normal mice. In addition, the
      Kp,brain values in Mdr1a/1b(-/-)/Bcrp(-/-) mice were not drastically different
      from those previously reported in Mdr1a/1b(-/-) mice, suggesting that brain
      penetration of aripiprazole and dehydroaripiprazole can be affected by P-gp, but
      with little synergistic effect of BCRP.

PMID- 24666335
TI  - Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous
      administration in patients with advanced and/or metastatic solid tumors.
AB  - The disposition and metabolism of a Chk-1 inhibitor (LY2603618) was characterized
      following a 1-h intravenous administration of a single 250-mg dose of
      [14C]LY2603618 (50 uCi) to patients with advanced or metastatic solid tumors.
      LY2603618 was well tolerated with no clinically significant adverse events. Study
      was limited to three patients due to challenges of conducting ADME studies in
      patients with advanced cancer. Plasma, urine and feces were analyzed for
      radioactivity, LY2603618 and metabolites. LY2603618 had a half-life of 10.5 h and
      was the most abundant entity in plasma, accounting for approximately 69% of total
      plasma radioactivity. The second most abundant metabolites, H2 and H5, accounted
      for <10% of total circulating radioactivity. The major route of clearance was via
      CYP450 metabolism. The mean total recovery of radioactivity was 83%, with
      approximately 72% of the radioactivity recovered in the feces and approximately
      11% in the urine. LY2603618 represented approximately 6% and 3% of the
      administered dose in feces and urine, respectively. A total of 12 metabolites
      were identified. In vitro phenotyping indicated that CYP3A4 was predominantly
      responsible for the metabolic clearance of LY2603618. Additionally, aldehyde
      oxidase was involved in the formation of a unique human and non-human primate
      metabolite, H5.

PMID- 24666337
TI  - Is being the first ever 'better' than being the best?

PMID- 24666336
TI  - Neutrophils from vasculitis patients exhibit an increased propensity for
      activation by anti-neutrophil cytoplasmic antibodies.
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in
      ANCA-associated vasculitis (AAV) by stimulating polymorphonuclear leucocytes
      (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this
      study was to investigate if PMNs from AAV patients are stimulated more readily by
      ANCA compared with PMNs from healthy controls (HCs). Differences in ANCA
      characteristics that can account for different stimulation potential were also
      studied. PMNs from five AAV patients and five HCs were stimulated with 10
      different immunoglobulins (Ig)Gs, purified from PR3-ANCA-positive patients, and
      ROS production, degranulation and neutrophil extracellular trap (NET) formation
      was measured. ANCA levels, affinity and clinical data of the AAV donors were
      recorded. The results show that PMNs from AAV patients produce more intracellular
      ROS (P = 0.019), but degranulate to a similar extent as PMNs from HCs. ROS
      production correlated with NET formation. Factors that may influence the ability
      of ANCA to activate PMNs include affinity and specificity for N-terminal
      epitopes. In conclusion, our results indicate that PMNs from AAV patients in
      remission behave quite similarly to HC PMNs, with the exception of a greater
      intracellular ROS production. This could contribute to more extensive NET
      formation and thus an increased exposure of the ANCA autoantigens to the immune
      system. 

PMID- 24666338
TI  - Use of continuous veno-venous haemodiafiltration therapy in dabigatran overdose.
AB  - CONTEXT: Dabigatran etexilate is one of the newer oral anticoagulants and a
      direct thrombin inhibitor. Concerns regarding dabigatran's use include its lack
      of validated laboratory markers for measuring its anticoagulation effect, the
      impact of renal impairment on its clearance, and the lack of effective strategies
      for reversal of anticoagulation. Hemodialysis has been utilized to reverse the
      anticoagulant effects of dabigatran in therapeutic doses. However, hemodialysis
      may not be feasible in hemodynamically unstable patients. There is little data on
      clearance rates of dabigatran by continuous renal replacement therapies. CASE
      DETAILS: A 66-year-old male presented following a poly-pharmacy overdose of 9 g
      of dabigatran in combination with metoprolol, amlodipine, olmesartan, and
      moxonidine. Eleven hours post overdose extracorporeal elimination was implemented
      as the patient developed worsening coagulopathy with an elevated international
      normalized ratio of 11 IU, an activated partial thromboplastin time of 115 s, and
      had renal impairment with a creatinine of 158 MUmol/L. As the patient was
      hemodynamically unstable, continuous veno-venous hemodiafiltration was preferred
      over intermittent hemodialysis. Renal replacement therapy was performed for 32 h
      in total and the patient made a full recovery with no hemorrhagic complications
      or end organ injury. This patient developed a peak serum dabigatran level of 1560
      ng/ml, 11 h postoverdose. Clearance of dabigatran via continuous veno-venous
      hemodiafiltration was calculated, using both the recovery and A-V pair methods,
      with a mean clearance of 58.1 and 31.9 ml/h, respectively, and a calculated mean
      extraction ratio of 0.2. CONCLUSION: There are few case reports and little
      experience when dabigatran is taken in overdose. This is a case report of a large
      dabigatran overdose presenting data on the extraction ratio and clearance of
      dabigatran using continuous veno-venous hemodiafiltration.

PMID- 24666339
TI  - Exotic snake bites in the Czech Republic--Epidemiological and clinical aspects
      during 15-year period (1999-2013).
AB  - Only one natural venomous snake-the adder viper-lives in the central European
      region and its bite is usually associated only with mild course of envenoming.
      Cases of envenoming caused by exotic snakes among their breeders are clinically
      more important. OBJECTIVE: The aim of this study was to analyze the
      epidemiological and clinical aspects of registered venomous bites caused by
      exotic snakes in the Czech Republic over a period of 15 years (1999-2013).
      MATERIALS AND METHODS: This is an observational case series. Data have been
      collected retrospectively from a database and medical charts of the Toxinology
      Center belonging to the General University Hospital in Prague. RESULTS: In total,
      87 cases of exotic snakebites caused by 34 venomous snake species were registered
      during the study period, coming from 18 genera of Elapinae, Viperinae, and
      Crotalinae subfamilies. In the cohort, 29 patients (33.3%) developed systemic
      envenoming and 17 (19.5%) were treated with antivenom. Ten cases of envenoming
      (11.5%) were considered as potentially life threatening. No patient died due to
      envenoming caused by exotic snake bites during the study period. Four
      illustrative cases of envenoming (Echis pyramidum, Dendroaspis polylepis,
      Protobothrops mangshanensis, and Proatheris superciliaris) are described in
      detail. CONCLUSION: Bites caused by exotic snakes resulted in serious and life
      threatening envenomings in some patients. Early transfer to the Center, antivenom
      administration, and support of failing organ functions contributed to favorable
      outcome of victims.

PMID- 24666340
TI  - Modified bowel preparation regimen for use in second-generation colon capsule
      endoscopy in patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: We have reported that second-generation colon capsule
      endoscopy (CCE-2) might be feasible for assessing the severity of mucosal
      inflammation in ulcerative colitis (UC). However, because of the low rate (69%)
      of complete evaluation of the colon and owing to inadequate cleansing. We believe
      that the method of bowel preparation could be improved by reducing volume. In the
      present study, we attempted to improve the colon-cleansing regimen in order to
      optimize the usefulness of CCE-2 in the management of UC patients. METHODS:
      Twenty patients with histologically confirmed UC were enrolled. Patients took a
      maximum 2.2 L lavage solution (polyethylene glycol solution and magnesium
      citrate) in two or three divided doses. To assess the effectiveness of the
      modified bowel preparation regimen, we evaluated the rate of total
      colonobservation, the effectiveness of bowel cleansing, andinterobserver
      agreement in assessing UC disease activity. We used a four-point grading scale
      (poor, fair, good, and excellent) for evaluating the quality of bowel cleansing.
      Matts' endoscopic score was used to evaluate disease activity. RESULTS: The rate
      of total colon observation was 85%, and 15 patients (75%) excreted the CCE-2
      within 8 h. The proportion of excellent plus good cleansing was approximately
      60%. There was a substantial interobserver agreement (kappa = 0.777) in
      assessment of overall cleansing, which was still substantial at the fair
      cleansing level (kappa = 0.700). CONCLUSION: Using CCE-2, the modified bowel
      preparation regimen, with reduced volume has the potential to succeed in the
      evaluation of mucosal severity in UC.

PMID- 24666341
TI  - Facile preparation and thermoelectric properties of Bi2Te3 based alloy
      nanosheet/PEDOT:PSS composite films.
AB  - Bi2Te3 based alloy nanosheet (NS)/poly(3,4-ethylenedioxythiophene):poly(4
      styrenesulfonate) (PEDOT:PSS) composite films were prepared separately by spin
      coating and drop casting techniques. The drop cast composite film containing 4.10
      wt % Bi2Te3 based alloy NSs showed electrical conductivity as high as 1295.21
      S/cm, which is higher than that (753.8 S/cm) of a dimethyl sulfoxide doped
      PEDOT:PSS film prepared under the same condition and that (850-1250 S/cm) of the
      Bi2Te3 based alloy bulk material. The composite film also showed a very high
      power factor value, ~32.26 MUWm(-1) K(-2). With the content of Bi2Te3 based alloy
      NSs increasing from 0 to 4.10 wt %, the electrical conductivity and Seebeck
      coefficient of the composite films increase simultaneously. 

PMID- 24666342
TI  - Effect of maternal iron status on the number of CD34+ stem cells harvested from
      umbilical cord blood.
AB  - BACKGROUND: Hematopoietic progenitor cells (HPCs) from umbilical cord blood (UCB)
      are an alternative source of stem cells. However an adequate number of HPCs must
      be harvested from each UCB sample to make therapeutic applications possible. This
      study investigated the impact of selected maternal indices (in particular iron
      status) on the number of CD34+ cells collected in the UCB. STUDY DESIGN AND
      METHODS: Blood samples were collected from 91 matched mother and umbilical cord
      pairs and analyzed for full blood count, iron status, and C-reactive protein.
      Viable CD34 enumeration was performed on the cord blood samples. RESULTS: Low
      CD34+ cell counts were associated with higher maternal serum ferritin (SF), older
      mothers, lower UCB white blood cell count (WCC), lower UCB nucleated red blood
      cells (NRBCs), and lower birthweight. Maternal SF correlated with maternal
      variables of iron status and RBC indices, newborn weight, placental weight, and
      NRBCs/100 WCC. CONCLUSION: This study indicates that lower numbers of CD34+ cells
      are more likely to occur when collected from mothers with higher SF. This finding
      suggests that maternal SF and associated iron status play a significant, but as
      yet undefined, role in the generation of CD34+ cells in UCB.

PMID- 24666343
TI  - Soft ionization chemical analysis of secondary organic aerosol from green leaf
      volatiles emitted by turf grass.
AB  - Globally, biogenic volatile organic compound (BVOC) emissions contribute 90% of
      the overall VOC emissions. Green leaf volatiles (GLVs) are an important component
      of plant-derived BVOCs, including cis-3-hexenylacetate (CHA) and cis-3-hexen-1-ol
      (HXL), which are emitted by cut grass. In this study we describe secondary
      organic aerosol (SOA) formation from the ozonolysis of dominant GLVs, their
      mixtures and grass clippings. Near-infrared laser desorption/ionization aerosol
      mass spectrometry (NIR-LDI-AMS) was used for chemical analysis of the aerosol.
      The chemical profile of SOA generated from grass clippings was correlated with
      that from chemical standards of CHA and HXL. We found that SOA derived from HXL
      most closely approximated SOA from turf grass, in spite of the approximately 5*
      lower emission rate of HXL as compared to CHA. Ozonolysis of HXL results in
      formation of low volatility, higher molecular weight compounds, such as
      oligomers, and formation of ester-type linkages. This is in contrast to CHA,
      where the hydroperoxide channel is the dominant oxidation pathway, as oligomer
      formation is inhibited by the acetate functionality. 

PMID- 24666345
TI  - Water-soluble pillar[7]arene: synthesis, pH-controlled complexation with
      paraquat, and application in constructing supramolecular vesicles.
AB  - By the introduction of 14 anionic carboxylate groups at its two rims, a water
      soluble pillar[7]arene (WP7) was synthesized. Its pH-controlled complexation with
      paraquat G1 in water was investigated. Host WP7 and guest G1 formed a 1:1
      [2]pseudorotaxane with a high association constant of (2.96 +/- 0.31) * 10(9) M(
      1) in water. Furthermore, we took advantage of this novel molecular recognition
      motif to fabricate a supra-amphiphile based on WP7 and an amphiphilic paraquat
      derivative G2. The morphologies and sizes of self-assemblies of G2 and WP7?G2
      were identified by transmission electron microscopy and dynamic light scattering.

PMID- 24666344
TI  - Haptoglobin, alpha-thalassaemia and glucose-6-phosphate dehydrogenase
      polymorphisms and risk of abnormal transcranial Doppler among patients with
      sickle cell anaemia in Tanzania.
AB  - Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv)
      of basal intracranial vessels and is used clinically to detect stroke risk in
      children with sickle cell anaemia (SCA). Co-inheritance in SCA of alpha
      thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) polymorphisms is
      reported to associate with high CBFv and/or risk of stroke. The effect of a
      common functional polymorphism of haptoglobin (HP) is unknown. We investigated
      the effect of co-inheritance of these polymorphisms on CBFv in 601 stroke-free
      Tanzanian SCA patients aged <24 years. Homozygosity for alpha-thalassaemia 3.7
      deletion was significantly associated with reduced mean CBFv compared to wild
      type (beta-coefficient -16.1 cm/s, P = 0.002) adjusted for age and survey year.
      Inheritance of 1 or 2 alpha-thalassaemia deletions was associated with decreased
      risk of abnormally high CBFv, compared to published data from Kenyan healthy
      control children (Relative risk ratio [RRR] = 0.53 [95% confidence interval
      (CI):0.35-0.8] & RRR = 0.43 [95% CI:0.23-0.78]), and reduced risk of abnormally
      low CBFv for 1 deletion only (RRR = 0.38 [95% CI:0.17-0.83]). No effects were
      observed for G6PD or HP polymorphisms. This is the first report of the effects of
      co-inheritance of common polymorphisms, including the HP polymorphism, on CBFv in
      SCA patients resident in Africa and confirms the importance of alpha-thalassaemia
      in reducing risk of abnormal CBFv. 

PMID- 24666347
TI  - Self-assembly of intramolecular charge-transfer compounds into functional
      molecular systems.
AB  - Highly polarized compounds exhibiting intramolecular charge transfer (ICT) are
      used widely as nonlinear optical (NLO) materials and red emitters and in organic
      light emitting diodes. Low-molecular-weight donor/acceptor (D/A)-substituted ICT
      compounds are ideal candidates for use as the building blocks of hierarchically
      structured, multifunctional self-assembled supramolecular systems. This Account
      describes our recent studies into the development of functional molecular systems
      with well-defined self-assembled structures based on charge-transfer (CT)
      interactions. From solution (sensors) to the solid state (assembled structures),
      we have fully utilized intrinsic and stimulus-induced CT interactions to
      construct these functional molecular systems. We have designed some organic
      molecules capable of ICT, with diversity and tailorability, that can be used to
      develop novel self-assembled materials. These ICT organic molecules are based on
      a variety of simple structures such as perylene bisimide, benzothiadiazole,
      tetracyanobutadiene, fluorenone, isoxazolone, BODIPY, and their derivatives. The
      degree of ICT is influenced by the nature of both the bridge and the
      substituents. We have developed new methods to synthesize ICT compounds through
      the introduction of heterocycles or heteroatoms to the pi-conjugated systems or
      through extending the conjugation of diverse aromatic systems via another
      aromatic ring. Combining these ICT compounds featuring different D/A units and
      different degrees of conjugation with phase transfer methodologies and solvent
      vapor techniques, we have self-assembled various organic nanostructures,
      including hollow nanospheres, wires, tubes, and ribbonlike architectures, with
      controllable morphologies and sizes. For example, we obtained a
      noncentrosymmetric microfiber structure that possessed a permanent dipole along
      its fibers' long axis and a transition dipole perpendicular to it; the
      independent NLO responses of this material can be separated and tuned
      spectroscopically and spatially. The ready processability and intrinsically high
      NLO efficiency of these microfibers offer great opportunities for applications in
      photonic devices. We have also designed molecular sensors based on changes in the
      efficiency of the ICT process upon complexation of an analyte with the D or A
      moieties in the ICT compounds. Such sensors, which display evident Stokes shifts
      or changes in quantum yields or fluorescence lifetimes, have promise for
      applications in chemical and biological recognition and sensing. In this Account,
      we shed light on the structure-function relationships of these functional
      molecular systems with well-defined self-assembled structures based on ICT
      interactions. The encouraging results that we have obtained suggest that such
      self-assembled ICT molecular materials can guide the design of new nanostructures
      and materials from organic systems, and that these materials, across a range of
      compositions, sizes, shapes, and functionalities, can potentially be applied in
      the fields of electronics, optics, and optoelectronics.

PMID- 24666348
TI  - A new alpha-glucosidase inhibitor from Achillea fragrantissima (Forssk.) Sch.
      Bip. growing in Egypt.
AB  - alpha-Glucosidase inhibitors (AGIs) represent a class of oral antidiabetic drugs
      that delay the absorption of ingested carbohydrates, reducing the postprandial
      glucose and insulin peaks to reach normoglycaemia. In this study, a bioassay
      guided fractionation of the ethanolic extract of the aerial parts of Achillea
      fragrantissima (Forssk.) Sch. Bip. growing in Egypt led to the isolation of a new
      potent AGI; acacetin-6-C-(6"-acetyl-beta-D-glucopyranoside)-8-C-alpha-L
      arabinopyranoside (5) alongside with four known compounds: chondrillasterol (1),
      quercetin-3,6,7-trimethyl ether (chrysosplenol-D) (2), isovitexin-4'-methyl ether
      (3) and isovitexin (4). The structure of the new compound (5) was elucidated on
      the basis of its spectral data, including HR-FAB-MS, UV, (1)H NMR, (13)C NMR,
      (1)H-(1)H COSY, HSQC and HMBC. The new compound (5) exhibited the most
      significant alpha-glucosidase inhibitory activity (IC50 1.5 +/- 0.09 MUg/mL).
      Under the assay conditions, all the tested compounds were more potent than the
      positive control acarbose (IC50 224 +/- 2.31 MUg/mL).

PMID- 24666346
TI  - mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse.
AB  - The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC1) is a
      serine and threonine kinase that regulates cell growth, survival, and
      proliferation. mTORC1 is a master controller of the translation of a subset of
      mRNAs. In the central nervous system mTORC1 plays a crucial role in mechanisms
      underlying learning and memory by controlling synaptic protein synthesis. Here,
      we review recent evidence suggesting that the mTORC1 signaling pathway promotes
      neuroadaptations following exposure to a diverse group of drugs of abuse
      including stimulants, cannabinoids, opiates, and alcohol. We further describe
      potential molecular mechanisms by which drug-induced mTORC1 activation may alter
      brain functions. Finally, we propose that mTORC1 is a focal point shared by drugs
      of abuse to mediate drug-related behaviors such as reward seeking and excessive
      drug intake, and offer future directions to decipher the contribution of the
      kinase to mechanisms underlying addiction. Recent studies suggesting that
      exposure to diverse classes of drugs of abuse as well as exposure to drug
      associated memories lead to mTORC1 kinase activation in the limbic system. In
      turn, mTORC1 controls the onset and the maintenance of pathological
      neuroadaptions that underlie several features of drug addiction such as drug
      seeking and relapse. Therefore, we propose that targeting mTORC1 and its
      effectors is a promising strategy to treat drug disorders. 

PMID- 24666349
TI  - TCA cycle activity in Staphylococcus aureus is essential for iron-regulated
      synthesis of staphyloferrin A, but not staphyloferrin B: the benefit of a second
      citrate synthase.
AB  - Staphylococcus aureus elaborates two citrate-containing siderophores,
      staphyloferrin A (SA) and staphyloferrin B (SB), that enhance growth under iron
      restriction, yet, paradoxically, expression of the TCA cycle citrate synthase,
      CitZ, is downregulated during iron starvation. Iron starvation does, however,
      result in expression of SbnG, recently identified as a novel citrate synthase
      that is encoded from within the iron-regulated SB biosynthetic locus, suggesting
      an important role for SbnG in staphyloferrin production. We demonstrate that
      during growth of S. aureus in iron-restricted media containing glucose, SB is
      produced but, in contrast, SA production is severely repressed; accordingly, SB
      deficient mutants grow poorly in these media. Hypothesizing that reduced TCA
      cycle activity hinders SA production, we show that a citZ mutant is capable of SB
      synthesis, but not SA synthesis, providing evidence that SbnG does not generate
      citrate for incorporation into SA. A citZ sbnG mutant synthesizes neither
      staphyloferrin, is severely compromised for growth in iron-restricted media, and
      is significantly more impaired for virulence than either of the single-deletion
      mutants. We propose that SB is the more important of the two siderophores for S.
      aureus insofar as it is synthesized, and supports iron-restricted growth, without
      need of TCA cycle activity. 

PMID- 24666350
TI  - Mast cells as possible targets of propranolol therapy: an immunohistological
      study of beta-adrenergic receptors in infantile haemangiomas.

PMID- 24666351
TI  - Academic challenges and positive aspects: perceptions of male nursing students.
AB  - BACKGROUND: Nursing shortage remains a global issue that emphasizes the need for
      both male and female nurses. Understanding the educational experiences of male
      nursing students may help in recruiting and retaining male nurses in the nursing
      profession. AIM: The aim of this study was to explore the challenges and positive
      aspects that undergraduate male nursing students encounter during the course of
      their study. METHODS: A qualitative research design using inductive content
      analysis approach was used to explore perceptions of 20 undergraduate male
      nursing students in a baccalaureate nursing programme at a major public
      university in Jordan. RESULTS: Content analysis revealed two major themes:
      challenges (academic difficulties, biased policies, no social life, negative
      views of nursing and negative self-view) and positive aspects (personal benefits
      of studying nursing, every home need a nurse and nursing is a science).
      DISCUSSION: The findings added new insights and knowledge regarding the
      educational experiences of undergraduate male nursing students in a developing
      country, which is an understudied population. Understanding the challenges and
      positive aspects of nursing education from the perspectives of undergraduate male
      nursing students may help nursing educators better understand their students'
      educational experiences and help clarify their roles and responsibilities in
      dealing with these issues. CONCLUSION: Nursing as a career should continue to be
      a viable choice for both male and female students to address global nursing
      shortages. This can be ensured by decreasing challenges and supporting positive
      aspects that nursing students face during their nursing education. IMPLICATIONS
      FOR NURSING AND HEALTH POLICY: Higher education policy makers can use the
      findings of this study to appreciate the challenges that university students
      face. They can also reconsider existing policies that may hinder the acceptance
      of male student into nursing programmes and contribute to educational challenges.

PMID- 24666352
TI  - Two-piece zirconia implants supporting all-ceramic crowns: a prospective clinical
      study.
AB  - OBJECTIVES: The aim of this prospective clinical study is to evaluate the safety
      and efficacy of a new all-ceramic implant system to replace missing teeth in
      partially edentulous patients. MATERIAL AND METHODS: Thirty-two partially
      edentulous, systemically healthy patients were treated with 49 two-piece zirconia
      implants (ZERAMEX((r)) T Implant System). Zirconia abutments were connected with
      adhesive resin cement. Single-unit full-ceramic crowns were cemented. The cases
      have been followed for 588 +/- 174 days after loading (range 369-889 days). All
      patients have been re-evaluated 1 year after loading. RESULTS: The cumulative
      survival rate 1 year after loading was 87% implants. All failures were the result
      of aseptic loosening, and no implants were lost after the first year. The results
      of the other cases were good, and the patients were very satisfied. The
      cumulative soft tissue complication rate was 0%, the cumulative technical
      complication rate was 4% implants, the cumulative complication rate for bone loss
      >2 mm was 0%, and the cumulative esthetic complication rate was 0%. Including the
      data from 20 patients treated with an earlier version of the system, an over-all
      2-year cumulative survival rate of 86% was calculated for a total of 76 two-piece
      zirconia implants supporting all-ceramic crowns in 52 patients. CONCLUSIONS:
      Replacement of single teeth in the posterior area was possible with this new full
      ceramic implant system. Failures were due to aseptic loosening.

PMID- 24666353
TI  - Chronobiology and competitive sports: recent studies and future perspectives.

PMID- 24666355
TI  - Effect of Luting Agents on Retention of Dental Implant-Supported Prostheses.
AB  - To evaluate the retentive strength of 7 different luting agents in cement
      retained implant abutment/analog assemblies. Fifty-six externally hexed dental
      implant abutment/analog assemblies and cast superstructures were divided randomly
      into 7 groups for cementation with each of the 7 luting agents. Five definitive
      cements tested were zinc phosphate cement, All-Bond 2, Maxcem, RelyX Luting
      cement, HY-Bond, and two provisional cements, ImProv and Premier. Cast
      superstructures were cemented onto the implant abutments and exposed to 1000
      thermal cycles (0 degrees C-55 degrees C) and 100 000 cycles on a chewing
      simulator (75 N load). A universal testing machine was used to measure cement
      failure load of the assembled specimens. Cement failure load was evaluated with 1
      way ANOVA and Duncan's multiple range analysis. Significant differences in cement
      failure loads were measured (P < .0001). Post hoc testing with Duncan's multiple
      range indicated 4 separate groupings. Maxcem and All-Bond 2 were comparable,
      having the greatest load failure. RelyX and zinc phosphate cement were analogous,
      and higher than HY-Bond. Improv and Premier constituted a pair, which
      demonstrated the lowest retentive values. Within the limitations of this in vitro
      study, Maxcem and All-Bond 2 are good candidates for cement-retained implant
      prostheses while concerning retention. 

PMID- 24666354
TI  - Solid-phase synthesis and hybrization behavior of partially 2'/3'-O-acetylated
      RNA oligonucleotides.
AB  - Synthesis of partially 2'/3'-O-acetylated oligoribonucleotides has been
      accomplished by using a 2'/3'-O-acetyl orthogonal protecting group strategy in
      which non-nucleophilic strong-base (DBU) labile nucleobase protecting groups and
      a UV-light cleavable linker were used. Strong-base stability of the photolabile
      linker allowed on-column nucleobase and phosphate deprotection, followed by a
      mild cleavage of the acetylated oligonucleotides from the solid support with UV
      light. Two 17nt oligonucleotides, which were synthesized possessing one specific
      internal 2'- or 3'-acetyl group, were used as synthetic standards in a recent
      report from this laboratory detailing the prebiotically plausible ligation of RNA
      oligonucleotides. In order to further investigate the effect of 2'/3'-O-acetyl
      groups on the stability of RNA duplex structure, two complementary bis-acetylated
      RNA oligonucleotides were also expediently obtained with the newly developed
      protocols. UV melting curves of 2'-O-acetylated RNA duplexes showed a consistent
      ~3.1  degrees C decrease in Tm per 2'-O-acetyl group.

PMID- 24666356
TI  - Modelling effects of candidate genes on complex traits as variables over time.
AB  - In this study, changes in gene effects for milk production traits were analysed
      over time. Such changes can be expected by investigating daily milk production
      yields, which increase during the early phase of lactation and then decrease.
      Moreover, additive polygenic effects on milk production traits estimated in other
      studies differed throughout the 305 days of lactation, clearly indicating changes
      in the genetic determination of milk production throughout this period. Our study
      focused on particular candidate genes known to affect milk production traits and
      on the estimation of potential changes in the magnitude of their effects over
      time. With two independent data sets from Holstein-Friesian and Jersey breeds, we
      show that the effects of the DGAT1:p.Lys232Ala polymorphism on fat and protein
      content in milk change during lactation. The other candidate genes considered in
      this study (leptin receptor, leptin and butyrophilin, subfamily 1, member A1)
      exhibited effects that vary across time, but these could be observed in only one
      of the breeds. Longitudinal modelling of SNP effects enables more precise
      description of the genetic background underlying the variation of complex traits.
      A gene that changes the magnitude or even the sign of its effect cannot be
      detected by a time-averaged model. This was particularly evident when analysing
      the effect of butyrophilin, missed by many previous studies, which considered
      butyrophilin's effect as constant over time.

PMID- 24666357
TI  - Serum autoantibodies directed against transglutaminase-2 have a low avidity
      compared with alloantibodies against gliadin in coeliac disease.
AB  - Coeliac disease is characterized by intolerance to gliadin and related gluten
      components present in wheat, barley and rye. Coeliac disease patients harbour
      antibodies directed against alloantigens such as gliadin, but also against the
      autoantigen transglutaminase-2 (TG2). The type and quality of antibody responses
      provides insight into the underlying immune activation processes. Therefore, in
      this study we have analysed the avidity of the antibody response directed against
      the autoantigen TG2 and compared this with antibody responses against the
      alloantigens gliadin and Escherichia coli. We observed that the immunoglobulin
      (Ig)A autoantibody response directed against TG2 is of low avidity compared with
      the IgA response against the alloantigens gliadin and E. coli in the same
      patients; the same was true for IgG, both in IgA-deficient and in -sufficient
      coeliac patients. The observed avidities appear not to be related to disease
      stage, antibody levels, age or duration of exposure to gluten. In conclusion, in
      coeliac disease there is a clear difference in avidity of the antibody responses
      directed against the auto- and alloantigens, indicating different regulation or
      site of initiation of these responses.

PMID- 24666359
TI  - Antibiotic susceptibility in benzalkonium chloride-resistant and -susceptible
      Listeria monocytogenes strains.
AB  - This study aimed to investigate whether Listeria monocytogenes strains with
      resistance to a commonly used biocide display any cross-resistance to
      antibiotics. Using pulsed-field gel electrophoresis (PFGE), 29 different PFGE
      types were previously identified in an Iberian pig abattoir and processing plant.
      Only three PFGE types were resistant to benzalkonium chloride (BAC), but they
      represented a significant proportion of the PFGE types surviving in the plant
      after 4 years. In the present study, a subset of 29 strains, representing the 29
      different PFGE types, underwent antibiotic susceptibility testing. Antibiotic
      susceptibility was assessed by Etest, utilizing 12 commonly prescribed
      antibiotics. All of the 29 strains were susceptible to all of the antibiotics
      tested. The study revealed that this group of different PFGE types of L.
      monocytogenes, including those resistant to BAC, possesses uniform sensitivity to
      antibiotics.

PMID- 24666360
TI  - Recent advances in the discovery of metallo-beta-lactamase inhibitors for beta
      lactam antibiotic-resistant reversing agents.
AB  - The overuse of antibiotics which exerts the selective pressure for bacterial
      pathogens has facilitated the spread of antibiotics' resistance. Metallo-beta
      lactamases (MbetaLs) are zinc enzymes produced by an increasing number of
      bacterial pathogens. They can readily cleave carbapenems and most other beta
      lactams that are mainstays of therapy for bacterial infections. MbetaL-conferred
      resistance to antibiotics is most worrisome due to MbetaLs exhibiting very broad
      spectrum resistance. Therefore, the bacteria carrying MbetaLs have recently
      become a significant clinical threat. No clinically useful MbetaLs inhibitor has
      been discovered yet. To address the serious threat to public health posed by the
      MbetaL-conferred resistance to antibiotics, novel effective MbetaL inhibitors are
      urgently needed. This review mainly describes various MbetaL inhibitors, giving
      special attention to their antibacterial activity, mechanisms of action,
      structure-activity relationships and synergetic effect with clinically available
      antibiotics. 

PMID- 24666362
TI  - Myeloid sarcoma (chloroma) masquerading as typhlitis.

PMID- 24666361
TI  - Predictors of local adverse effects caused by topical tretinoin cream 0.1% in the
      Veterans Affairs Topical Tretinoin Chemoprevention trial.
AB  - BACKGROUND: Topical tretinoin is commonly prescribed, but its frequent adverse
      effects are barriers to use. Predictors of resistance or susceptibility to
      retinoid irritation are not known. OBJECTIVE: To identify baseline patient
      characteristics associated with adverse effects of topical tretinoin. METHODS:
      This cohort study used data collected from 324 participants in the Veterans
      Affairs Topical Tretinoin Chemoprevention trial who were randomized to apply
      tretinoin cream on the face and ears. Univariate and multivariate logistic
      regression models were used to examine the associations between baseline
      characteristics and local adverse effects. RESULTS: One hundred and ninety-seven
      patients (61% of those randomized to tretinoin) reported local adverse effects
      within 6 months. Clinical signs of severe photodamage at baseline [odds ratio
      (OR) 0.15, 95% confidence interval (CI) 0.04-0.54] and history of acne (OR 0.46,
      95% CI 0.27-0.77) were associated with a decreased risk of adverse effects to
      tretinoin. The use of other topical medications at enrolment (OR 1.88, 95% CI
      1.15-3.08) predicted an increase in adverse effects. CONCLUSIONS: In this study
      population, the common indications of topical tretinoin treatment were associated
      with lower risks of adverse effects. The concurrent use of other topical
      medications may worsen irritation caused by tretinoin.

PMID- 24666363
TI  - Highly asymmetric bromocyclization of tryptophol: unexpected accelerating effect
      of DABCO-derived bromine complex.
AB  - Highly asymmetric bromocyclization of tryptophol by using chiral anionic phase
      transfer catalyst and DABCO-derived brominating reagent is described.
      Optimization of the reaction conditions revealed that the reaction rate was
      accelerated together with improvement of enantioselectivity by addition of
      catalytic DABCO-derived brominating reagent. From tryptophol, 3-bromofuroindoline
      could be directly obtained in excellent enantioselectivities by employing this
      novel methodology. 

PMID- 24666364
TI  - Island bat diets: does it matter more who you are or where you live?
AB  - Differences in body size, echolocation call frequency and location may result in
      diet partitioning among bat species. Comparisons between island populations are
      one way to evaluate these competing hypotheses. We conducted a species-level diet
      analysis of three Rhinolophus and one Hipposideros species on the Philippine
      islands of Cebu, Bohol and Siquijor. We identified 655 prey (MOTUs) in the guano
      from 77 individual bats. There was a high degree of overlap among species' diets
      despite differences in body size and call frequency. For example, the diet of the
      3 g-Hipposideros pygmaeus (mean CF = 102 kHz) exhibited a diet overlap higher
      than expected by chance with all three Rhinolophus species, even the 13 g
      Rhinolophus inops (mean CF = 54 kHz). We observed more convergence in diet
      between Rhinolophus species and H. pygmaeus than between Rhinolophus species
      themselves, which may be explained by the broad diet of H. pygmaeus. There was
      less dietary overlap between Rhinolophus virgo from two islands than between R.
      virgo and congeners from Cebu. These data suggest that location causes
      convergence in diet, but specific species characteristics may drive niche
      specialization. The complex interplay between location and the perceptual ability
      of each species leads to a situation where simple explanations, for example body
      size, do not translate into predictable prey partitioning. In particular, our
      observations raise interesting questions about the foraging strategy and
      adaptability of the tiny H. pygmaeus.

PMID- 24666366
TI  - Successful use of miniphotopheresis for the treatment of graft-versus-host
      disease.
AB  - BACKGROUND: Extracorporeal photopheresis (ECP) is an important cell-based therapy
      for graft-versus-host disease (GVHD); however, the blood volume required per
      treatment to achieve a clinical response is unknown. STUDY DESIGN AND METHODS: We
      developed a mini-ECP technique (mini-ECP) using only 100 to 200 mL of whole blood
      for patients with contraindications for apheresis or low body weight. Sixteen
      patients (n=13 acute, n=3 chronic GVHD) with a median body weight of 19 kg
      (range, 7-48 kg) received 460 mini-ECP treatments with a median duration of 115
      days (range, 49-973 days). RESULTS: Mini-ECP was well tolerated, and acute GVHD
      resolved completely in nine of 13 patients and partially in two patients but not
      in two patients. Cutaneous chronic GVHD exhibited a mixed response (one complete,
      one partial, and one no response). CONCLUSION: These results indicate mini-ECP as
      a novel and less invasive therapy for patients with GVHD and contraindications
      for apheresis.

PMID- 24666365
TI  - Nociceptin/orphanin FQ peptide receptor antagonist JTC-801 reverses pain and
      anxiety symptoms in a rat model of post-traumatic stress disorder.
AB  - BACKGROUND AND PURPOSE: Single-prolonged stress (SPS), a rat model of post
      traumatic stress disorder (PTSD), also induces long-lasting hyperalgesia
      associated with hypocortisolism and elevated nociceptin/orphanin FQ (N/OFQ)
      levels in serum and CSF. Here, we determined the effect of JTC-801 (N-(4-amino-2
      methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride), a
      nociceptin/orphanin FQ peptide (NOP) receptor antagonist, on symptoms of pain and
      anxiety in rats after SPS exposure, and examined N/OFQ-NOP receptor system
      changes. EXPERIMENTAL APPROACH: Male Sprague Dawley rats received JTC-801 (6 mg
      kg(-1) i.p., once daily) during days 7-21 of SPS. The ability of JTC-801 to
      inhibit N/OFQ-stimulated [(35) S]-GTPgammaS binding was confirmed in rat brain
      membranes. Anxiety-like behaviour and pain sensitivity were monitored by changes
      in elevated plus maze performance and withdrawal responses to thermal and
      mechanical stimuli. Serum corticosterone and N/OFQ content in CSF, serum and
      brain tissues were determined by radioimmunoassay; NOP receptor protein and gene
      expression in amygdala, hippocampus and periaqueductal grey (PAG) were examined
      by immunoblotting and real-time PCR respectively. KEY RESULTS: JTC-801 treatment
      reversed SPS-induced mechanical allodynia, thermal hyperalgesia, anxiety-like
      behaviour and hypocortisolism. Elevated N/OFQ levels in serum, CSF, PAG and
      hippocampus at day 21 of SPS were blocked by JTC-801; daily JTC-801 treatment
      also reversed NOP receptor protein and mRNA up-regulation in amygdala and PAG.
      CONCLUSION AND IMPLICATIONS: JTC-801 reversed SPS-induced anxiety- and pain-like
      behaviours, and NOP receptor system up-regulation. These findings suggest that
      N/OFQ plays an important role in hyperalgesia and allodynia maintenance after
      SPS. NOP receptor antagonists may provide effective treatment for co-morbid PTSD
      and pain. LINKED ARTICLES: This article is part of a themed section on Opioids:
      New Pathways to Functional Selectivity. To view the other articles in this
      section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24666367
TI  - Involvement of astroglial glutamate-glutamine shuttle in modulation of the jaw
      opening reflex following infraorbital nerve injury.
AB  - To evaluate the mechanisms underlying orofacial motor dysfunction associated with
      trigeminal nerve injury, we studied the astroglial cell activation following
      chronic constriction injury (CCI) of the infraorbital nerve (ION)
      immunohistochemically, nocifensive behavior in ION-CCI rats, and the effect of
      the glutamine synthase (GS) blocker methionine sulfoximine (MSO) on the jaw
      opening reflex (JOR), and also studied whether glutamate-glutamine shuttle
      mechanism is involved in orofacial motor dysfunction. GFAP-immunoreactive (IR)
      cells were observed in the trigeminal motor nucleus (motV) 3 and 14 days after
      ION-CCI, and the nocifensive behavior and JOR amplitude were also strongly
      enhanced at these times. The number of GS- and GFAP-IR cells was also
      significantly higher in ION-CCI rats on day 7. The amplitude and duration of the
      JOR were strongly suppressed after MSO microinjection (m.i.) into the motV
      compared with that before MSO administration in ION-CCI rats. After MSO
      administration, the JOR amplitude was strongly suppressed, and the duration of
      the JOR was shortened. Forty minutes after m.i. of glutamine, the JOR amplitude
      was gradually returned to the control level and the strongest attenuation of the
      suppressive effect of MSO was observed at 180 min after glutamine m.i. In
      addition, glutamine also attenuated the MSO effect on the JOR duration, and the
      JOR duration was extended and returned to the control level thereafter. The
      present findings suggest that astroglial glutamate-glutamine shuttle in the motV
      is involved in the modulation of excitability of the trigeminal motoneurons
      affecting the enhancement of various jaw reflexes associated with trigeminal
      nerve injury. 

PMID- 24666368
TI  - Increased micronuclei and nuclear abnormalities in buccal mucosa and oxidative
      damage in saliva from patients with chronic and aggressive periodontal diseases.
AB  - BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic bacterial infection
      characterized by connective tissue breakdown and alveolar bone destruction
      because of inflammatory and immune response caused by periodontopathogens and
      long-term release of reactive oxygen species. A high number of reactive oxygen
      species result in periodontal tissue damage through multiple mechanisms such as
      lipid peroxidation, protein denaturation and DNA damage. The aim of this study
      was to evaluate DNA and oxidative damage in subjects with chronic or aggressive
      periodontitis and healthy controls. MATERIAL AND METHODS: Buccal mucosa cells and
      whole saliva were collected from 160 subjects, who were divided into three
      groups: subjects with chronic periodontitis (CP) (n = 58), subjects with
      aggressive periodontitis (AgP) (n = 42) and a control group (n = 60). DNA damage
      was determined by counting micronuclei (MN) and nuclear abnormalities (NAs) in
      exfoliated cells, including binucleated cells, cells with nuclear buds and
      karyolitic, karyorrhectic, condensed chromatin and pyknotic cells. The degree of
      oxidative stress was determined by quantifying 8-hydroxy-2'-deoxyguanosine (8
      OHdG) in whole saliva. RESULTS: Subjects with CP or AgP presented significantly
      more ( p < 0.05) MN and NAs and higher levels of 8-OHdG ( p < 0.05) compared with
      the control group. CONCLUSION: Our results indicate that subjects with
      periodontitis (CP or AgP) exhibited an increase in the frequency of MN, NAs and 8
      OHdG, which is directly related to DNA damage. In addition, a positive
      correlation exists between oxidative stress produced by periodontitis disease and
      MN.

PMID- 24666369
TI  - A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal
      tissue metabolism and cross-species dosimetry.
AB  - A PBPK model for naphthalene in the rat and human that incorporates a hybrid CFD
      PBPK description of the upper respiratory tract was developed to support cross
      species dosimetry comparisons of naphthalene concentrations and tissue normalized
      rate of metabolism in the nasal respiratory and olfactory epithelium, lung and
      liver. In vitro measurements of metabolic rates from microsomal incubations
      published for rat and monkey (surrogate for human) were scaled to the specific
      tissue based on the tissue microsomal content and volume of tissue. The model
      reproduces time courses for naphthalene blood concentrations from intravenous and
      inhalation exposures in rats and upper respiratory tract extraction data in both
      naive rats and rats pre-treated to inhibit nasal metabolism. This naphthalene
      model was applied to estimate human equivalent inhalation concentrations (HECs)
      corresponding to several NOAELs or LOAELs for the non-cancer effects of
      naphthalene in rats. Two approaches for cross-species extrapolation were
      compared: (1) equivalence based on tissue naphthalene concentration and (2)
      equivalence based on amount metabolized per minute (normalized to tissue volume).
      At the NOAEL of 0.1 ppm, the regional gas dosimetry ratio (RGDR) based on
      naphthalene concentration was 0.18 for the dorsal olfactory region; however, the
      RGDR rises to 5.4 when based on the normalized amount metabolized due to the
      lower of expression of CYP isozymes in the nasal epithelium of primates and
      humans. The resulting HEC is 0.12 ppm (0.63 mg/m(3)) continuous exposure at the
      rat NOAEL of 0.1 ppm (6 h/day, 5 days/week).

PMID- 24666370
TI  - Natural male contraceptive: phytochemical investigation and anti-spermatogenic
      activity of Pistia stratiotes Linn.
AB  - This work is an attempt to explore the anti-spermatogenic activity of Pistia
      stratiotes and to investigate it as a male contraceptive. The prepared extracts
      were screened for the presence of alkaloids, glycosides, steroids, flavonoids,
      saponin and phenolic compounds. To assess the anti-spermatogenic activity, mice
      were orally administered with the various extracts of P. stratiotes (dose: 100
      and 200 mg/kg body weight/day, for 45 days) and the most active, ethanolic
      extract was subjected to the isolation of phytoconstituent responsible for the
      activity. Diethyl ether fraction of ethanolic extract was taken to isolate a
      saponin, sitosterol-3-O-[2,4-di-O-acetyl-6-O-stearyl-beta-D-glucopyranoside].
      Anti-spermatogenic activity of the isolated saponin was evaluated at a dose of 50
      mg/kg body weight/day, for 45 days. The treatment caused significant decrease (P
      < 0.01) in the weight of reproductive organs (testis, epididymis and seminal
      vesicle). The sperm count, sperm viability and serum testosterone levels were
      significantly lowered compared with that of the control group.

PMID- 24666371
TI  - Use of mTOR inhibitors in the treatment of malignancies.
AB  - INTRODUCTION: mTOR and its effectors are central regulators of cellular
      metabolism in malignant cells and control mRNA translation that ultimately leads
      to generation of mitogenic proteins. Efforts to target this pathway have been
      ongoing for over a decade and have had a substantial impact in the management of
      certain patients with solid tumors. Although activity of mTOR inhibitors has been
      established in several trials, inability to predict responses remains a limiting
      factor for the successful incorporation of these agents in the treatment of a
      variety of malignancies. AREAS COVERED: Recent clinical findings are discussed
      and studies focused on advanced phase development of mTOR inhibitors are
      summarized. The emergence of precision medicine approaches and the effects that
      such approaches may have on prospective selection of patients for treatment with
      mTOR inhibitors are discussed. Also, potential approaches and future prospects to
      improve responses to mTOR inhibitors by modulating other parallel mitogenic
      pathways essential for malignant cell proliferation are discussed. EXPERT
      OPINION: Selective targeting of the mTOR pathway offers significant clinical
      advantage in subsets of patients with diverse malignancies. Approaches to enhance
      responses by concomitant targeting of resistance pathways and/or predict
      responses via identification of molecular markers should substantially impact
      this area in the near and distant future.

PMID- 24666372
TI  - Layered tantalum oxynitride nanorod array carpets for efficient
      photoelectrochemical conversion of solar energy: experimental and DFT insights.
AB  - Anodically fabricated tantalum oxide (Ta2O5) nanorod array carpets are converted
      into the corresponding tantalum oxynitride (TaON) through nitridation in an
      ammonia atmosphere. The measured optical bandgap energy of TaON is ~2.3 eV, which
      is also confirmed via the density functional theory calculations. When used to
      photoelectrochemically split water (AM 1.5G illumination, 1 M KOH, and 0.6 V
      applied DC bias), the multilayer nanorod films show visible-light incident photon
      conversion efficiencies (IPCE) as high as 7.5%. The enhanced photochemical
      activity is discussed in terms of the ordered one-dimensional morphology as well
      as the electron effective mass in TaON and Ta2O5. 

PMID- 24666374
TI  - MUC 4-negative FUS-CREB3L2 rearranged low-grade fibromyxoid sarcoma.

PMID- 24666373
TI  - Metal specificity of cyanobacterial nickel-responsive repressor InrS: cells
      maintain zinc and copper below the detection threshold for InrS.
AB  - InrS is a Ni(II)-responsive, CsoR/RcnR-like, DNA-binding transcriptional
      repressor of the nrsD gene, but the Ni(II) co-ordination sphere of InrS is unlike
      Ni(II)-RcnR. We show that copper and Zn(II) also bind tightly to InrS and in
      vitro these ions also impair InrS binding to the nrsD operator-promoter. InrS
      does not respond to Zn(II) (or copper) in vivo after 48 h, when Zn(II) sensor
      ZiaR responds, but InrS transiently responds (1 h) to both metals. InrS conserves
      only one (of two) second co-ordination shell residues of CsoR (Glu98 in InrS).
      The allosteric mechanism of InrS is distinct from Cu(I)-CsoR and conservation of
      deduced second shell residues better predicts metal specificity than do the metal
      ligands. The allosteric mechanism of InrS permits greater promiscuity in vitro
      than CsoR. The factors dictating metal-selectivity in vivo are that KNi(II) and
      DeltaG(C)(Ni(II)-InrS.DNA) are sufficiently high, relative to other metal
      sensors, for InrS to detect Ni(II), while the equivalent parameters for copper
      may be insufficient for copper-sensing in Synechocystis (at 48 h). InrS K(Zn(II))
      (5.6 * 10(-13)  M) is comparable to the sensory sites of ZiaR (and Zur), but
      DeltaG(C)(Zn(II)-InrS.DNA) is less than DeltaG(C)(Zn(II)-ZiaR.DNA) implying that
      relative to other sensors, DeltaG(C)(Zn(II)-Sensor.DNA) rather than K(Zn(II))
      determines the final detection threshold for Zn(II).

PMID- 24666375
TI  - A trophic cascade induced by predatory ants in a fig-fig wasp mutualism.
AB  - A trophic cascade occurs when predators directly decrease the densities, or
      change the behaviour, of herbivores and thus indirectly increase plant
      productivity. The predator-herbivore-plant context is well known, but some
      predators attack species beneficial to plants (e.g. pollinators) and/or enemies
      of herbivores (e.g. parasites), and their role in the dynamics of mutualisms
      remains largely unexplored. We surveyed the predatory ant species and studied
      predation by the dominant ant species, the weaver ant Oecophylla smaragdina,
      associated with the fig tree Ficus racemosa in southwest China. We then tested
      the effects of weaver ants on the oviposition behaviour of pollinating and non
      pollinating fig wasps in an ant-exclusion experiment. The effects of weaver ants
      on fig wasp community structure and fig seed production were then compared
      between trees with and without O. smaragdina. Oecophylla smaragdina captured more
      non-pollinating wasps (Platyneura mayri) than pollinators as the insects arrived
      to lay eggs. When ants were excluded, more non-pollinators laid eggs into figs
      and fewer pollinators entered figs. Furthermore, trees with O. smaragdina
      produced more pollinator offspring and fewer non-pollinator offspring, shifting
      the community structure significantly. In addition, F. racemosa produced
      significantly more seeds on trees inhabited by weaver ants. Oecophylla smaragdina
      predation reverses the dominance of the two commonest wasp species at the egg
      laying stage and favours the pollinators. This behavioural pattern is mirrored by
      wasp offspring production, with pollinators' offspring dominating figs produced
      by trees inhabited by weaver ants, and offspring of the non-pollinator P. mayri
      most abundant in figs on trees inhabited by other ants. Overall, our results
      suggest that predation by weaver ants limits the success of the non-pollinating
      P. mayri and therefore indirectly benefits the mutualism by increasing the
      reproductive success of both the pollinators and the plant. Predation is thus a
      key functional factor that can shape the community structure of a pollinator
      plant mutualistic system. 

PMID- 24666376
TI  - Mechanisms of immune injury and heterogeneity of bone marrow hematopoietic cells
      island in patients with auto-immuno-related hematocytopenia.
AB  - Because of environmental pollution more and more people are suffered with auto
      immuno-related hematocytopenia (AIRH). Serum IL-12, IL-17, and IFN-gamma levels
      were detected by ELISA and lymphocyte subsets were analyzed by flow cytometry.
      Peroxidase (POX) and HLA-DR of immune cells were detected by cytochemical and
      immunochemical staining. Cells expressing anti-human IgG, FcgammaR II, MR, and
      other molecules in HI were detected by immunofluorescence. Serum IL-12, IL-17,
      and IFN-gamma levels of patients were significantly higher than control group.
      Lymphocyte subsets of patients showed that the percentages of CD19+ B cells and
      CD3+ CD8+ T cell in peripheral blood were both significantly elevated. HI were
      mainly classified into three types, in these three types of hematopoietic cells
      island, peroxidase, and HLA-DR expression varied. Hematopoietic cells with
      pathological changes expressed anti-human IgG. The immunocytes with different
      levels of immunomolecules adhered captured and devoured abnormal hematopoietic
      cells. Immune cells expressed IL-12, IL-17A, and IL-17RA, leading to inflammatory
      injury of hematopoietic cells. HI destroys cells which connect auto-antibodies.
      Immune cells in HI express a variety of immune molecules, promote cell immune
      responses, and amplify the inflammatory reaction by ADCC effect or phagocytosis.
      These ultimately destruct directly and damage indirectly hematopoietic cells. 

PMID- 24666377
TI  - Gonadal function in males with autoimmune Addison's disease and autoantibodies to
      steroidogenic enzymes.
AB  - Steroidogenic enzyme autoantibodies (SEAbs) are frequently present and are
      markers of autoimmune premature ovarian failure (POF) in females with autoimmune
      Addison's disease (AAD). The prevalence and significance of SEAbs in males with
      AAD have not yet been defined. We studied the prevalence of SEAbs in a large
      cohort of males with AAD and assessed the relationship between SEAbs positivity
      and testicular function. A total of 154 males with AAD (mean age 34 years) were
      studied. SEAbs included autoantibodies to steroid-producing cells (StCA),
      detected by immunofluorescence, and steroid 17alpha-hydroxylase (17alpha-OHAbs)
      and side chain cleavage enzyme (SCCAbs) measured by immunoprecipitation assays.
      Gonadal function was evaluated by measuring follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin
      (SHGB), anti-mullerian hormone (AMH) and inhibin-B (I-B). Twenty-six males, 10
      SEAbs((+)) and 16 SEAbs((-)), were followed-up for a mean period of 7.6 years to
      assess the behaviour of SEAbs and testicular function. SEAbs were found in 24.7%
      of males with AAD, with the highest frequency in patients with autoimmune
      polyendocrine syndrome type 1 (APS-1). The levels of reproductive hormones in 30
      SEAbs((+)) males were in the normal range according to age and were not
      significantly different compared to 55 SEAbs((-)) males (P > 0.05). During follow
      up, both SEAbs((+)) and SEAbs((-)) patients maintained normal testicular
      function. SEAbs were found with high frequency in males with AAD; however, they
      were not associated with testicular failure. This study suggests that the
      diagnostic value of SEAbs in males with AAD differs compared to females, and this
      may be related to the immunoprivileged status of the testis.

PMID- 24666378
TI  - A prospective study of changes in oral health-related quality of life during
      immediate function implant procedures for edentulous individuals.
AB  - OBJECTIVE: The aim of this prospective clinical study was to evaluate
      longitudinal changes in oral health-related quality of life (OHRQoL) attributable
      to fixed dental prostheses during All-on-4((r)) treatment in one or both jaws.
      MATERIALS AND METHODS: Ten patients underwent placement of four or six endosteal
      dental implants on the basis of the All-on-4((r)) treatment concept in the
      edentulous maxilla or both jaws and immediate loading with acrylic interim
      prostheses. The prostheses were replaced after 3-6 months, and definitive
      prostheses with titanium framework and reinforced resin facing were fixed after
      another 5 months or more. The subjects completed the shortened Japanese version
      of the Oral Health Impact Profile (OHIP-J14) before the surgery (T0), 1 week
      after the initial (T1) and secondary (T2) interim prostheses were placed, and 3
      months after definitive prosthesis placement (T3). Complete data of nine subjects
      were analyzed with the Wilcoxon signed-rank test. RESULTS: The total OHIP-J14
      score significantly reduced only at T3 (P < 0.05). "Functional limitation,"
      "physical pain," "physical disability," and "psychological disability" scores
      significantly decreased at T3, and "psychological discomfort" scores also
      significantly dropped at T2. "Social disability" and "handicap" scores remained
      unchanged throughout. CONCLUSION: Fixed definitive prostheses with metal
      framework are more effective than fixed all-acrylic prostheses in improving
      OHRQoL during All-on-4((r)) treatment.

PMID- 24666379
TI  - Comparisons of ultrafine and fine particles in their associations with biomarkers
      reflecting physiological pathways.
AB  - Using a quasi-experimental opportunity offered by greatly restricted air
      pollution emissions during the Beijing Olympics compared to before and after the
      Olympics, we conducted the current study to compare ultrafine particles (UFPs)
      and fine particles (PM2.5) in their associations with biomarkers reflecting
      multiple pathophysiological pathways linking exposure and cardiorespiratory
      events. Number concentrations of particles (13.0-764.7 nm) and mass
      concentrations of PM2.5 were measured at two locations within 9 km from the
      residence and workplace of 125 participating Beijing residents. Each participant
      was measured 6 times for biomarkers of autonomic function (heart rate, systolic
      and diastolic blood pressures), hemostasis (von Willebrand factor, soluble CD40
      ligand, and P-selectin), pulmonary inflammation and oxidative stress (exhaled
      nitric oxide and exhaled breath condensate pH, malondialdehyde, and nitrite), and
      systemic inflammation and oxidative stress (urinary malondialdehyde and 8-hydroxy
      2'-deoxyguanosine, plasma fibrinogen, and white blood cells). Linear mixed models
      were used to estimate associations of biomarkers with UFPs and PM2.5 measured 1-7
      days prior to biomarker measurements (lags). We found that the correlation
      coefficient for UFPs at two locations (~ 9 km apart) was 0.45, and at the same
      location, the correlation coefficient for PM2.5 vs UFPs was -0.18. Changes in
      biomarker levels associated with increases in UFPs and PM2.5 were comparable in
      magnitude. However, associations of certain biomarkers with UFPs had different
      lag patterns compared to those with PM2.5, suggesting that the ultrafine size
      fraction (<= 100 nm) and the fine size fraction (~ 100 nm to 2.5 MUm) of PM2.5
      are likely to affect PM-induced pathophysiological pathways independently.

PMID- 24666380
TI  - Molecular characterization of "inconsistent" variants of Salmonella Typhimurium
      isolated in Italy.
AB  - Salmonella 4,[5],12:i:- is a variant of Salmonella Typhimurium, which lacks the
      expression of phase-2 flagellar antigen, generally associated with the deletion
      of the fljB gene. Additional mechanisms involving the fljAB operon ( fljA, fljB,
      and hin genes) lead to the lack of expression of phase-2 flagellar antigens also
      in Salmonella strains harboring the fljB gene. For 20 S. 4,[5],12:i:- strains,
      defined as "inconsistent" Salmonella Typhimurium variants since they had
      phenotypically behaved as monophasic, even though the fljB gene was conserved,
      the fljAB operon was characterized in order to explain the ineffective expression
      of the phase-2 flagellar antigen. The monophasic phenotype for a first group of
      strains (9) was likely due to the absence of the hin gene, leading to the
      inhibited switch between the expression of phase-1 and phase-2 flagellar genes.
      For a second group of strains (5), the monophasic phenotype could be attributed
      to nonconservative point mutations identified in fljA and hin genes, which could
      hamper the proper expression of invertase gene and the fljA, acting as repressor
      of the phase-1 flagellar gene. Finally, for a last group of inconsistent strains
      (6), a plausible reason for their monophasic phenotype was not found, since the
      genes involved in the expression of phase-2 flagellar antigen were fully
      conserved. Moreover, the collection of inconsistent Salmonella Typhimurium
      isolates investigated were characterized by distinct molecular profiles, as
      demonstrated by multiple-locus variable-number tandem repeat analysis, and
      phenotype variability, as demonstrated by phage-typing. This study highlights the
      usefulness of investigating the entire fljAB operon when a definitive
      identification of the monophasic or biphasic status of Salmonella Typhimurium
      strains is needed (for instance, in the context of epidemiological investigations
      aimed to identify the relatedness among strains).

PMID- 24666381
TI  - Anti-viral therapy for prevention of perinatal HBV transmission: extending
      therapy beyond birth does not protect against post-partum flare.
AB  - BACKGROUND: Antepartum anti-viral therapy (AVT) is often administered to prevent
      perinatal transmission of hepatitis B virus (HBV) infection. Little is known
      about the effect of AVT on post-partum flare rates and severity. AIM: To examine
      whether extending AVT beyond birth influences the post-partum course. METHODS:
      One hundred and one pregnancies in 91 women with HBV DNA levels >=log 7 IU/mL
      were included. AVT (initially lamivudine, later tenofovir disoproxil fumarate)
      was commenced from 32 weeks gestation and stopped soon after birth and at 12
      weeks post-partum. Outcomes according to post-partum treatment duration were
      examined: Group 1 = AVT <=4 weeks (n = 44), Group 2 = AVT >4 weeks (n = 43),
      Group 3 = no AVT (n = 14). RESULTS: The majority of women were HBeAg+ (97%),
      median age 29 years, baseline HBV DNA log 8.0 IU/mL and follow-up 48 weeks post
      partum. Post-partum treatment duration was 2 weeks for Group 1 and 12 weeks for
      Group 2, P < 0.01. Flare rates were not significantly different: Group 1 = 22/44
      (50%), Group 2 = 17/43 (40%) and Group 3 = 4/14 (29%), P = 0.32. Onset of flare
      was similar at 8/10/9 weeks post-partum for Groups 1/2/3 respectively, P = 0.34.
      The majority of flares spontaneously resolved. HBeAg seroconversion (n = 1/5/1 in
      Groups 1/2/3, P = 0.27) was not associated with treatment duration or the
      occurrence of a post-partum flare. CONCLUSIONS: Post-partum flares are common and
      usually arise early after delivery. They are often mild in severity and most
      spontaneously resolve. Extending anti-viral therapy does not protect against post
      partum flares or affect HBeAg seroconversion rates.

PMID- 24666383
TI  - A Prospective Noninterventional Study to Evaluate Survival and Success of Reduced
      Diameter Implants Made From Titanium-Zirconium Alloy.
AB  - Narrow diameter implants may be at increased risk of overload due to occlusal
      forces; therefore, implants with higher fatigue strength may be beneficial. The
      aim of this observational study was to evaluate survival and success of narrow
      diameter (O 3.3 mm) TiZr alloy (Roxolid, Institut Straumann AG, Basel,
      Switzerland) implants for 2 years in daily dental practice. This was a
      prospective, non-interventional, multicenter study; no specific patient inclusion
      or exclusion criteria were applied. Each patient received at least one TiZr
      implant; the treatment plan, including implant loading and final restoration, was
      at the investigator's discretion. The primary outcome was implant survival and
      success after 1 year. Secondary outcomes included 2-year survival and success and
      marginal bone level change. A total of 603 implants were placed in 357 patients.
      Cumulative survival and success rates were 97.8% and 97.6%, respectively, after 1
      year and 97.6% and 97.4%, respectively, after 2 years. Bone levels remained
      stable in the majority of patients, and soft tissue remained stable up to 2
      years. Within the limitations of a non-interventional study design, TiZr implants
      showed excellent survival and success with minimal bone loss up to 2 years in
      daily dental practice. The results compare favorably with those of small-diameter
      implants in controlled clinical trials. 

PMID- 24666382
TI  - E-cigarettes and unfair competition: a recent ruling in France.

PMID- 24666384
TI  - Duodenal villous morphology assessed using magnification narrow band imaging
      correlates well with histology in patients with suspected malabsorption syndrome.
AB  - BACKGROUND AND AIM: Narrow band imaging with magnification enables detailed
      assessment of duodenal villi and may be useful in predicting the presence of
      villous atrophy or normal villi. We aimed to assess the morphology of duodenal
      villi using magnification narrow band imaging and correlate it with histology
      findings in patients with clinically suspected malabsorption syndrome. METHODS:
      Patients with clinical suspicion of malabsorption presenting at a tertiary care
      center were prospectively recruited in this diagnostic intervention study.
      Patients underwent upper gastrointestinal endoscopy using magnification narrow
      band imaging. The villous morphology in the second part of the duodenum was
      assessed independently by two endoscopists and the presence of normal or atrophic
      villi was recorded. Biopsy specimen was obtained from the same area and was
      examined by two pathologists together. The sensitivity and specificity of
      magnification narrow band imaging in detecting the presence of duodenal villous
      atrophy was calculated and compared to the histology. RESULTS: One hundred
      patients with clinically suspected malabsorption were included in this study.
      Sixteen patients had histologically confirmed villous atrophy. The sensitivity
      and specificity of narrow band imaging in predicting villous atrophy was 87.5%
      and 95.2%, respectively, for one endoscopist. The corresponding figures for the
      second endoscopist were 81.3% and 92.9%, respectively. The interobserver
      agreement was very good with a kappa value of 0.87. CONCLUSION: Magnification
      narrow band imaging performed very well in predicting duodenal villous
      morphology. This may help in carrying out targeted biopsies and avoiding
      unnecessary biopsies in patients with suspected malabsorption.

PMID- 24666385
TI  - Brucellosis infection in an adult liver transplant recipient.

PMID- 24666386
TI  - Maternal hepatitis B and hepatitis C infection and neonatal neurological
      outcomes.
AB  - To examine the associations between maternal hepatitis B (HBV) and hepatitis C
      (HCV) infection status and selected infant neurological outcomes diagnosed at
      birth, we conducted a population-based, retrospective cohort study on singleton
      live births in Florida from 1998 to 2009. Primary exposures included maternal HBV
      and HCV monoinfection. The neurological outcomes included brachial plexus injury,
      cephalhematoma, foetal distress, feeding difficulties, intraventricular h
      aemorrhage and neonatal seizures. Multivariable logistic regression models were
      used to generate odds ratios (OR) and 95% confidence intervals (CI) that were
      adjusted for socio-demographic characteristics, risky behaviours, pregnancy
      complications and pre-existing medical conditions, and timing of delivery. The
      risk of an adverse neurological outcome was higher in infants born to mothers
      with hepatitis viral infection (7.2% for HCV, 5.0% for HBV), compared with
      infants of hepatitis virus-free mothers (4.2%). After adjusting for potential
      confounders, women with HBV were twice as likely to have infants who suffered
      from brachial plexus injury (OR = 2.04, 95% CI = 1.15-3.60), while those with HCV
      had an elevated odds of having an infant with feeding difficulties (OR: 1.32, 95%
      CI = 1.06-1.64) and a borderline increased likelihood for neonatal seizures (OR =
      1.74, 95% CI = 0.98-3.10). Additionally, HCV+ mothers had a 22% increased odds of
      having an infant with some type of adverse neurological outcome (OR: 1.22, 95% CI
      = 1.03-1.44). Our findings add to current understanding of the association
      between maternal HBV/HCV infections and infant neurological outcomes. Further
      research evaluating the role of maternal HBV and HCV infections (including
      viraemia, treatment) on pregnancy outcomes is warranted.

PMID- 24666387
TI  - Cell cycle inhibitors for the treatment of NSCLC.
AB  - INTRODUCTION: Lung cancer remains to be the leading cause of cancer-related death
      worldwide. Treatment of lung cancer still poses a significant challenge. Cell
      cycle is a tightly integrated process and is frequently aberrant in lung cancer.
      Cell cycle inhibitors have emerged as novel therapeutics, in anticipation of
      overcoming the unrestricted cell division and growth in lung cancer. AREAS
      COVERED: In this article, we first address the potential roles of cell cycle
      proteins and cell cycle deregulation in the development of lung cancer. The
      review then provides an overview for several major categories of cell cycle
      inhibitors with particular attention to their tolerability and disease control in
      early phases of lung cancer trials. EXPERT OPINION: Targeted agents against
      different components of cell cycle regulation, such as cyclin-dependent kinase,
      polo-like kinase, checkpoint kinase and aurora kinase, are currently in clinical
      development for lung cancer management. Their clinical benefits remain to be
      defined. When evaluated as single agents in lung cancer, cell cycle inhibitors
      are often associated with limited clinical activity and tolerable toxicities. The
      key challenges in the drug development are to understand resistance mechanisms
      and to identify predictive biomarkers that can potentially guide patient
      selection and optimize the utility of these targeted inhibitors.

PMID- 24666390
TI  - Parallel and combinatorial liquid-phase synthesis of alkylbiphenyls using
      pentaerythritol support.
AB  - Unfunctionalized alkylbiphenyls were fabricated by a parallel and combinatorial
      synthesis using pentaerythritol as a tetrapodal soluble support for a sulfonate
      based traceless multifunctional linker system. Nickel N-heterocyclic carbene
      catalyzed reactions of pentaerythritol tetrakis(biphenylsulfonate)s with primary
      alkylmagnesium bromides generated the alkylbiphenyl derivatives by desulfitative
      cleavage/cross-coupling of the C-S bond without any "memory" of the attachment on
      the support. Though the reactions were completed with sufficient yields in 12 h
      at room temperature, even with only 1.5 equiv of nucleophiles, they still
      retained the benefits of facile isolation observed in polymer-supported
      reactions. 

PMID- 24666389
TI  - Reduced levels of brain-derived neurotrophic factor contribute to synaptic
      imbalance during the critical period of respiratory development in rats.
AB  - Previously, our electrophysiological studies revealed a transient imbalance
      between suppressed excitation and enhanced inhibition in hypoglossal motoneurons
      of rats on postnatal days (P) 12-13, a critical period when abrupt neurochemical,
      metabolic, ventilatory and physiological changes occur in the respiratory system.
      The mechanism underlying the imbalance is poorly understood. We hypothesised that
      the imbalance was contributed by a reduced expression of brain-derived
      neurotrophic factor (BDNF), which normally enhances excitation and suppresses
      inhibition. We also hypothesised that exogenous BDNF would partially reverse this
      synaptic imbalance. Immunohistochemistry/single-neuron optical densitometry, real
      time quantitative PCR (RT-qPCR) and whole-cell patch-clamp recordings were done
      on hypoglossal motoneurons in brainstem slices of rats during the first three
      postnatal weeks. Our results indicated that: (1) the levels of BDNF and its high
      affinity tyrosine receptor kinase B (TrkB) receptor mRNAs and proteins were
      relatively high during the first 1-1.5 postnatal weeks, but dropped precipitously
      at P12-13 before rising again afterwards; (2) exogenous BDNF significantly
      increased the normally lowered frequency of spontaneous excitatory postsynaptic
      currents but decreased the normally heightened amplitude and frequency of
      spontaneous inhibitory postsynaptic currents (sIPSCs) during the critical period;
      (3) exogenous BDNF also decreased the normally heightened frequency of miniature
      IPSCs at P12-13; and (4) the effect of exogenous BDNF was partially blocked by
      K252a, a TrkB receptor antagonist. Thus, our results are consistent with our
      hypothesis that BDNF and TrkB play an important role in the synaptic imbalance
      during the critical period. This may have significant implications for the
      mechanism underlying sudden infant death syndrome. 

PMID- 24666392
TI  - Microenvironment regulation of pluripotent stem cell-derived neural progenitor
      aggregates by human mesenchymal stem cell secretome.
AB  - Neural progenitor cells (NPCs) derived from pluripotent stem cells (PSCs),
      including embryonic stem cells (ESCs) and induced PSCs, are promising cell source
      for the treatment of various neurological diseases. NPC derivation from PSCs is
      regulated by microenvironment factors that influence cell fate via paracrine and
      autocrine effects. In this study, ESC-derived NPC aggregates were replated in the
      secretomes of bone marrow-derived human mesenchymal stem cells (hMSCs) generated
      under hypoxia or normoxia to investigate the effects of hMSC secretome on NPC
      cellular behaviors. The results demonstrated that hMSC secretomes stimulated
      endogenous secretion of extracellular matrices from NPC aggregates and enhanced
      cell adhesion and proliferation. NPC functional differentiation measured by
      migration length, neurite extension, and the yield of neural and glial cells were
      also increased by threefold to fourfold. Inhibition of fibroblast growth factor
      2, transforming growth factor-beta1, and brain-derived neurotrophic factor
      signaling differentially reduced the adherent cell number, migration length, and
      neurite extension, suggesting the regulatory effects of a broad spectrum of hMSC
      derived factors. In summary, ESC-derived NPC aggregates in hypoxic hMSC
      secretomes may represent a suitable combination to promote the engraftment and
      neurogenesis in vivo. 

PMID- 24666393
TI  - The efficacy of the ultraviolet C pathogen inactivation system in the reduction
      of Babesia divergens in pooled buffy coat platelets.
AB  - BACKGROUND: Babesia spp. is an intraerythrocytic parasite that causes human
      babesiosis and its transmission by transfusion has been extensively demonstrated.
      The aim of this study was to ascertain the efficacy of an ultraviolet C (UVC)
      based pathogen inactivation system in the reduction of Babesia divergens-infected
      platelet (PLT) concentrates and to determine the parasite's ability to survive in
      PLT concentrates stored under blood bank conditions. STUDY DESIGN AND METHODS:
      This study was conducted using in vitro cultures of B. divergens. The detection
      limit of the culture assay was established and, subsequently, 15 buffy coat
      derived PLT concentrates (BC-PCs) were inoculated with 10(7) B. divergens
      infected red blood cells. Infected BC-PCs were irradiated with 0.2 J/cm(2) UVC
      light using the THERAFLEX UV-Platelets method (Macopharma). Viability and
      parasite growth were evaluated before and after inactivation. Culture growth
      kinetics were monitored by DNA incorporation of [(3) H]thymidine. The ability of
      B. divergens to survive in PLT concentrates was also analyzed. RESULTS: The limit
      of detection in cultures was established at 0.1 * 10(-6) % parasites. The
      THERAFLEX UV-Platelets system inactivated B. divergens to below the limit of
      detection in 12 of 15 BC-PCs (log reduction, >6.0) and to the limit of detection
      (log reduction, 5.0) in three of 15. It was also demonstrated that B. divergens
      remains viable in BC-PCs stored up to 7 days. CONCLUSION: Since B. divergens can
      survive in PLT concentrates and given the performance of UVC, this system could
      be considered as an alternative to prevent B. divergens and other Babesia species
      from being transmitted through PLT transfusions.

PMID- 24666391
TI  - In vivo opioid receptor heteromerization: where do we stand?
AB  - Opioid receptors are highly homologous GPCRs that modulate brain function at all
      levels of neural integration, including autonomous, sensory, emotional and
      cognitive processing. Opioid receptors functionally interact in vivo, but the
      underlying mechanisms involving direct receptor-receptor interactions, affecting
      signalling pathways or engaging different neuronal circuits, remain unsolved.
      Heteromer formation through direct physical interaction between two opioid
      receptors or between an opioid receptor and a non-opioid one has been postulated
      and can be characterized by specific ligand binding, receptor signalling and
      trafficking properties. However, despite numerous studies in heterologous
      systems, evidence for physical proximity in vivo is only available for a limited
      number of opioid heteromers, and their physiopathological implication remains
      largely unknown mostly due to the lack of appropriate tools. Nonetheless, data
      collected so far using endogenous receptors point to a crucial role for opioid
      heteromers as a molecular entity that could underlie human pathologies such as
      alcoholism, acute or chronic pain as well as psychiatric disorders. Opioid
      heteromers therefore stand as new therapeutic targets for the drug discovery
      field. LINKED ARTICLES: This article is part of a themed section on Opioids: New
      Pathways to Functional Selectivity. To view the other articles in this section
      visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24666394
TI  - Asymmetric synthesis of alpha-allyl-alpha-aryl alpha-amino acids by tandem
      alkylation/pi-allylation of alpha-iminoesters.
AB  - The first asymmetric synthesis of alpha-allyl-alpha-aryl alpha-amino acids by
      means of a three-component coupling of alpha-iminoesters, Grignard reagents, and
      cinnamyl acetate is reported. Notably, the enolate from the tandem process
      provides a much higher level of reactivity and selectivity than the same enolate
      generated via direct deprotonation, presumably due to differences in the
      solvation/aggregation state. A novel method for removal of a homoallylic amine
      protecting group delivers the free amine congeners. The alpha-allyl group offers
      a means to generate further valuable alpha-amino acid structures as exemplified
      by ring closing metathesis to generate a higher ring homologue of alpha-aryl
      proline. 

PMID- 24666395
TI  - In vitro antioxidant and antimicrobial activities of flavonoids from Panax
      notoginseng flowers.
AB  - Panax notoginseng and its flowers are both well-known traditional Chinese
      medicinal herbs. To date, antimicrobial and antioxidant activities of flavonoids
      from P. notoginseng flowers (PNF) remain unclear. In this study, antimicrobial
      and antioxidant activities of flavonoids from PNF were investigated. The crude
      flavonoids were purified using a column (25 cm * 1.5 cm) packed with AB-8
      macroporous adsorption resin. Compared with ascorbic acid, the purified
      flavonoids excelled in scavenging activities on 2,2'-azino-bis-3
      ethylbenzthiazoline-6-sulphonic acid, superoxide anion and hydroxyl radicals at
      0.2-1.0 mg/mL concentration. However, flavonoids exhibited weaker reducing power
      than ascorbic acid at 20-100 MUg/mL concentration. In addition, the flavonoids
      exhibited obvious inhibitory effects on Staphylococcus aureus, Aeromonas
      hydrophila and Pseudomonas aeruginosa. These results clearly indicate that
      flavonoids from PNF are effective in scavenging free radicals and have the
      potential to be used as antioxidants and antimicrobial agents, and also provide
      the theoretical data for supporting the use of PNF in food, pharmaceutical and
      cosmetics industries.

PMID- 24666396
TI  - Increasing skin cancer incidence in young, affluent, urban populations: a
      challenge for prevention.
AB  - BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in white
      people, but is registered inconsistently by population-based registries.
      OBJECTIVES: To analyse the changing profile of NMSC in a national population, to
      interpret evolving patterns of sun exposure and to recommend measures to reduce
      risk. METHODS: We analysed trends in the demographic, clinical and socioeconomic
      profile of > 50 000 cases of NMSC registered between 1994 and 2011 by the Irish
      National Cancer Registry, which aims to register all episodes of NMSC in the
      Irish population to a high degree of completeness. RESULTS: The incidence of
      cutaneous basal cell (BCC) and squamous cell carcinoma (SCC) was stable from 1994
      to 2002, but increased significantly (BCC more than SCC) in the subsequent
      decade. The largest relative increases in the incidence of BCC were in younger
      populations and in clothed body sites. The incidence of both cancers was lower in
      rural areas. Incidence of BCC and, to a lesser extent, of SCC, increased with
      increasing affluence in urban, but not in rural, areas. CONCLUSIONS: Recent
      increases in skin cancers on the trunk and limbs in younger people appear to be
      related to increasing affluence and consequent leisure-related, episodic sun
      exposure. This population is at high risk of subsequent skin cancers throughout
      life and will need active surveillance. As preventive programmes are cost
      effective in lowering the incidence of NMSC, they should be targeted at leisure
      exposure in young people. The recording of consistent international data on NMSC
      should also be a priority.

PMID- 24666397
TI  - Prevalence and correlates of erectile dysfunction in type 2 diabetes mellitus: a
      cross-sectional single-center study among Turkish patients.
AB  - OBJECTIVE: The aim of this study was to evaluate prevalence of erectile
      dysfunction (ED) in patients with type 2 diabetes mellitus (T2DM) in relation to
      vascular and neurogenic correlates. METHODS: A total of 116 males including T2DM
      patients [n=68; mean age, 56.7 (5.8) years] and age-matched healthy controls
      [n=48; mean age, 57.0 (6.6) years] were included in this cross-sectional single
      center study. Data on anthropometrics, blood biochemistry, concomitant
      hypertension, hyperlipidemia, and coronary artery disease (CAD) were recorded in
      each subject along with measurement of carotid artery intima media thickness
      (CIMT) and evaluation of erectile dysfunction (ED) via International Index of
      Erectile Function (IIEF-5) Questionnaire. A univariate analysis was performed to
      determine the relationship of cardiovascular risk factors and diabetes-related
      complications to ED. RESULTS: Patient and control groups were similar in terms of
      percentage patients with hyperlipidemia (51.5% and 39.6%, respectively) and CAD
      (33.8% and 22.9%, respectively), whereas concomitant hypertension was more common
      (P=0.05) and CIMT values were significantly higher (P=0.020) in patients with
      T2DM compared with controls. Polyneuropathy was noted in 46.2% of patients,
      nephropathy in 30.8%, and retinopathy in 33.8%. ED scores were significantly
      lower in patients than controls [14.3 (7.3) vs. 18.2 (6.3), P=0.004] with a
      significantly higher percentage of patients than controls in the category of
      severe dysfunction (29.4 vs. 10.4%, P=0.014). Univariate analysis revealed that
      diabetic polyneuropathy was the only factor to be associated with higher
      likelihood (93.3% in the presence and 60.0% in the absence of neuropathy) and
      severity (43.3% in the presence and 14.3% in the absence of neuropathy) of ED
      (P=0.004). CONCLUSION: Findings from the present cross-sectional single-center
      study revealed the prevalence of ED to be considerably higher in patients with
      T2DM than age-matched healthy controls, with identification of diabetic
      polyneuropathy as the only risk factor associated with higher likelihood and more
      severe forms of ED.

PMID- 24666398
TI  - Extrahepatic metabolism at the body's internal-external interfaces.
AB  - In general, xenobiotic metabolizing enzymes (XMEs) are expressed in lower levels
      in the extrahepatic tissues than in the liver, making the former less relevant
      for the clearance of xenobiotics. Local metabolism, however, may lead to tissue
      specific adverse responses, e.g. organ toxicities, allergies or cancer. This
      review summarizes the knowledge on the expression of phase I and phase II XMEs
      and transporters in extrahepatic tissues at the body's internal-external
      interfaces. In the lung, CYPs of families 1, 2, 3 and 4 and epoxide hydrolases
      are important phase I enzymes, while conjugation is less relevant. In skin, phase
      I-related enzymatic reactions are considered less relevant. Predominant skin XMEs
      are phase II enzymes, whereby glucuronosyltransferases (UGT) 1, glutathione-S
      transferase (GST) and N-acetyltransferase (NAT) 1 are important for
      detoxification. The intestinal epithelium expresses many transporters and phase I
      XME with high levels of CYP3A4 and CYP3A5 and phase II metabolism is mainly
      related to UGT, NAT and Sulfotransferases (SULT). In the kidney, conjugation
      reactions and transporters play a major role for excretion processes. In the
      bladder, CYPs are relevant and among the phase II enzymes, NAT1 is involved in
      the activation of bladder carcinogens. Expression of XMEs is regulated by several
      mechanisms (nuclear receptors, epigenetic mechanisms, microRNAs). However, the
      understanding why XMEs are differently expressed in the various tissues is
      fragmentary. In contrast to the liver - where for most XMEs lower expression is
      demonstrated in early life - the XME ontogeny in the extrahepatic tissues remains
      to be investigated.

PMID- 24666399
TI  - The glucagon-like peptide-1-based therapeutics exenatide and saxagliptin did not
      cause detrimental effects on the pancreas in mice, rats, dogs and monkeys.
AB  - AIMS: Recent reports in the literature have suggested that glucagon-like peptide
      1 (GLP-1)-based therapies may lead to increased risk of pancreatic pathology
      leading to chronic pancreatic injury and pancreatic neoplasia. Extensive non
      clinical and clinical safety testing was conducted to support the global
      development of exenatide twice daily, exenatide once weekly and saxagliptin. Our
      aim was to integrate these non-clinical data obtained with both mechanisms of GLP
      1-based drugs to provide complementary data regarding the potential for drug
      induced pancreatic safety signals. METHODS: More than 70 regulated non-clinical
      toxicology studies in rodents and non-rodents were conducted in accordance with
      International Conference on Harmonisation and US Food and Drug Administration
      guidance documents, current industry standards, animal welfare regulations and in
      compliance with Good Laboratory Practice regulations. Treatment duration was up
      to 2 years in rodents and up to 12 months in non-rodents using high doses
      representing large multiples of human exposures (up to 130* for exenatide and
      2200* for saxagliptin). Comprehensive pancreas assessments involved more than
      2400 pancreata from animals exposed to exenatide and over 1700 pancreata from
      animals exposed to saxagliptin. RESULTS: Neither exenatide nor saxagliptin
      treatment resulted in drug-related microscopic changes indicative of acute or
      chronic adverse effects (including neoplasia) in the endocrine or exocrine
      pancreas, at doses far exceeding the maximum human systemic exposures.
      CONCLUSIONS: These data substantially add to the weight of evidence supporting
      the lack of non-clinical drug-induced pancreatic safety signals in animals
      exposed to GLP-1-based therapies.

PMID- 24666400
TI  - The smell of good food: volatile infochemicals as resource quality indicators.
AB  - Foraging success generally depends on various environmental and physiological
      factors. Particularly for organisms with limited motility such as gastropods,
      food searching is a very cost-intensive process. As energy gain through foraging
      is dependent on both resource quality and quantity, consumers have to be able to
      differentiate between varying resource items. The effectiveness of food searching
      could be increased through the perception of diet-derived chemical signals that
      convey information about a food resource's quality over a certain distance. This
      strategy would clearly help to optimize movement decisions. In this study, we
      investigated the foraging behaviour of a freshwater gastropod towards volatile
      signal substances released from benthic algae grown under high and low nutrient
      availability, representing high and low food quality, using behavioural assays in
      the laboratory. Our results demonstrate that volatile organic compounds (VOCs)
      serve as foraging kairomones for these aquatic, benthic herbivores. Further, we
      were able to show for the first time that snails are able to differentiate
      between high- and low-quality food sources, only by the perception of food odours
      alone (volatile infochemicals). Gas chromatography coupled with mass spectrometry
      demonstrated quantitative as well as qualitative differences in the chemical
      composition of the VOCs bouquet, dependent on algal nutrient content. Our results
      suggest that the recognition of resource quality via the reception of signal
      substances is likely to be adaptive for consumers with low mobility to maximize
      ingestion of high-quality resources. 

PMID- 24666401
TI  - Restoration of peripheral blood natural killer and B cell levels in patients
      affected by rheumatoid and psoriatic arthritis during etanercept treatment.
AB  - Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-alpha agent used in
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on
      the effects of anti-TNF-alpha on peripheral blood cells. We aimed to evaluate
      peripheral blood cells in RA and PsA patients during ETN treatment and to explore
      their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients
      who started ETN were included into the study and evaluated prospectively before
      the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were
      studied in terms of disease activity score on 28 joints (DAS28), clinical
      response and laboratory findings. Natural killer (NK) cells, B cells and T cells
      were characterized by immunophenotyping. Both the RA and the PsA patients showed
      reduced NK and B cell count before ETN treatment compared with controls. A
      negative correlation was demonstrated between DAS28 and B cell count in RA
      patients at baseline. Sustained significant increase of NK and B cells up to
      normal levels was observed in RA and PsA patients along ETN treatment. Increase
      of NK cell count was associated with a good-moderate clinical response to ETN in
      both RA and PsA patients. During ETN treatment peripheral blood NK and B cells
      levels were restored in RA and PsA patients. Correlations between NK and B cells
      with disease activity were observed, suggesting that those effects could be
      mediated by ETN treatment. 

PMID- 24666403
TI  - Recently published hypertension guidelines of the JNC 8 panelists, the American
      Society of Hypertension/International Society of Hypertension and other major
      organizations: introduction to a focus issue of the Journal of Clinical
      Hypertension.

PMID- 24666402
TI  - A spatiotemporal study of gliosis in relation to depth electrode tracks in drug
      resistant epilepsy.
AB  - Key questions remain regarding the processes governing gliogenesis following
      central nervous system injury that are critical to understanding both beneficial
      brain repair mechanisms and any long-term detrimental effects, including
      increased risk of seizures. We have used cortical injury produced by intracranial
      electrodes (ICEs) to study the time-course and localization of gliosis and
      gliogenesis in surgically resected human brain tissue. Seventeen cases with ICE
      injuries of 4-301 days age were selected. Double-labelled immunolabelling using a
      proliferative cell marker (MCM2), markers of fate-specific transcriptional
      factors (PAX6, SOX2), a microglial marker (IBA1) and glial markers (nestin, GFAP)
      was quantified in three regions: zone 1 (immediate vicinity: 0-350 MUm), zone 2
      (350-700 MUm) and zone 3 (remote >=2000 MUm) in relation to the ICE injury site.
      Microglial/macrophage cell densities peaked at 28-30 days post-injury (dpi) with
      a significant decline in proliferating microglia with dpi in all zones. Nestin
      expressing cells (NECs) were concentrated in zones 1 and 2, showed the highest
      regenerative capacity (MCM2 and PAX6 co-expression) and were intimately
      associated with capillaries within the organizing injury cavity. There was a
      significant decline in nestin/MCM2 co-expressing cells with dpi in zones 1 and 2.
      Nestin-positive fibres remained in the chronic scar, and NECs with neuronal
      morphology were noted in older injuries. GFAP-expressing glia were more evenly
      distributed between zones, with no significant decline in density or
      proliferative capacity with dpi. Colocalization between nestin and GFAP in zone 1
      glial cells decreased with increasing dpi. In conclusion, NECs at acute injury
      sites are a proliferative, transient cell population with capacity for maturation
      into astrocytes with possible neuronal differentiation observed in older
      injuries.

PMID- 24666404
TI  - Designed synthesis of titania nanoparticles coated hierarchially ordered
      macro/mesoporous silica for selective enrichment of phosphopeptides.
AB  - Metal oxide affinity chromatography (MOAC) is a powerful technique in
      phosphoproteome research. However, the achievement of highly specific enrichment
      and sensitive detection of phosphopeptide by MOAC remains a big challenge since
      the lack of high specificity and large binding capacity of conventional MOAC
      materials. In this work, a new MOAC material, TiO2-coated hierarchically ordered
      macro/mesoporous silica (denoted as HOMMS@TiO2) composites, was prepared via a
      facile process. The HOMMS@TiO2 composites were demonstrated to have low limit of
      detection (8 fmol) and great specificity with a very rapid enrichment speed
      (within 1 min). These experimental results have demonstrated that the HOMMS@TiO2
      exhibit great potential in phosphoproteome research. 

PMID- 24666405
TI  - Epstein-Barr virus BZLF1 gene polymorphisms: malignancy related or geographically
      distributed variants?
AB  - The ubiquitous Epstein-Barr virus (EBV) is related to the development of several
      lymphoid and epithelial malignancies and is also the aetiological agent for
      infectious mononucleosis (IM). BZLF1, an immediate early gene, plays a key role
      in modulating the switch from latency to lytic replication, hence enabling viral
      propagation. Polymorphic variations in the coded protein have been studied in
      other geographical regions in a search for viral factors that are inherent to
      malignancies and differ from those present in benign infections. In the present
      study, in samples of paediatric patients with benign IM and paediatric patients
      with malignant lymphomas, we detected previously described sequence variations as
      well as distinctive sequence polymorphisms from our region. By means of
      phylogenetic reconstruction, we characterized new phylogenetically distinct
      variants. Moreover, we described an association between specific variants and the
      studied pathologies in our region, particularly variant BZLF1-A2 with lymphomas
      and BZLF1-C with IM. Additionally, length polymorphisms within intron 1 were also
      assessed and compared between pathologies resulting in an association between 29
      bp repeated units and lymphomas. In conclusion, this is the first report to
      characterize BZLF1 gene polymorphisms in paediatric patients from our
      geographical region and to suggest the association of these polymorphisms with
      malignant lymphomas. 

PMID- 24666406
TI  - Impact of forestry on total and methyl-mercury in surface waters: distinguishing
      effects of logging and site preparation.
AB  - Forestry operations can increase the export of mercury (both total and methyl) to
      surface waters. However, little is known about the relative contribution of
      different forestry practices. We address this question using a paired-catchment
      study that distinguishes the effects of site preparation from the antecedent
      logging. Runoff water from three catchments, two harvested and one untreated
      control, was sampled biweekly during one year prior to logging, two years after
      logging, and three years after site preparation. The logging alone did not
      significantly increase the concentrations of either total or methyl-mercury in
      runoff, but export increased by 50-70% in one of the harvested catchments as a
      consequence of increased runoff volume. The combined effects of logging and site
      preparation increased total and methyl-mercury concentrations by 30-50% relative
      to preharvest conditions in both treated catchments. The more pronounced
      concentration effect after site preparation compared to logging could be related
      to site preparation being conducted during summer. This caused more soil
      disturbance than logging, which was done during winter with snow covering the
      ground. The results suggest that the cumulative impact of forest harvest on
      catchment mercury outputs depends on when and how forestry operations are
      implemented. 

PMID- 24666407
TI  - Criterion validity, reliability and clinical responsiveness of the
      CareConnections Functional Index.
AB  - This study established the criterion validity, test-retest reliability and
      responsiveness of the CareConnections Functional Index (CCFI). The CCFI is
      composed of four body-region specific subscales, measuring functional ability.
      Reference standards included the Neck Disability Index; Modified Oswestry
      Disability Index; Quick Disabilities of the Arm, Shoulder and Hand and the Lower
      Extremity Functional Scale. One hundred subjects per body region were enrolled.
      Subject's rated their perceived improvement based on the 15-point Global Rating
      of Change questionnaire. Minimal clinically important differences (MCID) were
      calculated via receiver operator characteristic curve. Test-retest reliability
      coefficients were good to excellent. Validity correlations with the reference
      standard measures were acceptable (r > 0.7) for all subscales. MCID for the
      cervical subscale = 7 points, lumbar = 8 points, upper extremity = 16 points and
      lower extremity = 11 points. The results of this study support the use of the
      CCFI in outpatient physical therapy practice as a responsive tool with good
      reliability and validity. The results also indicate that future work should focus
      on the impact of baseline patient factors that may affect future outcome.

PMID- 24666408
TI  - Concurrent validity and reliability of the Simple Goniometer iPhone app compared
      with the Universal Goniometer.
AB  - OBJECTIVES: The aim of this study was to assess the concurrent validity and
      reliability of the Simple Goniometer (SG) iPhone(r) app compared to the Universal
      Goniometer (UG). DESIGN: Within subject comparison design comparing the UG with
      the SG app. SETTING: James Cook University, Townsville, Queensland, Australia.
      PARTICIPANTS: Thirty-six volunteer participants, with a mean age of 60.6 years
      (SD 6.2). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Thirty-six
      participants performed three standing lunges during which the knee joint angle
      was measured with the SG app and the UG. RESULTS: There were no significant
      differences in the measures of individual knee joint angles between the UG and
      the SG app. Pearson correlations of 0.96-0.98 and intraclass correlation
      coefficients of 0.97-0.99 (95% confidence interval: 0.95-1.00) were recorded for
      all measures. Using the Bland-Altman method, the standard error of the mean of
      the differences and the standard deviation of the mean of the differences were
      low. CONCLUSION: The measurements from the SG iPhone(r) app were reliable and
      possessed concurrent validity for this sample and protocol when compared to the
      UG.

PMID- 24666409
TI  - The validity of using an electrocutaneous device for pain assessment in patients
      with cervical radiculopathy.
AB  - The purpose of this study was to evaluate the validity and preference for
      assessing pain magnitude with electrocutaneous testing (ECT) compared to the
      visual analogue scale (VAS) and Borg CR10 scale in men and women with cervical
      radiculopathy of varying sensory phenotypes. An additional purpose was to
      investigate ECT sensory and pain thresholds in men and women with cervical
      radiculopathy of varying sensory phenotypes. This is a cross-sectional study of
      34 patients with cervical radiculopathy. Scatterplots and linear regression were
      used to investigate bivariate relationships between ECT, VAS and Borg CR10
      methods of pain magnitude measurement as well as ECT sensory and pain thresholds.
      The use of the ECT pain magnitude matching paradigm for patients with cervical
      radiculopathy with normal sensory phenotype shows good linear association with
      arm pain VAS (R(2) = 0.39), neck pain VAS (R(2) = 0.38), arm pain Borg CR10 scale
      (R(2) = 0.50) and neck pain Borg CR10 scale (R(2) = 0.49) suggesting acceptable
      validity of the procedure. For patients with hypoesthesia and hyperesthesia
      sensory phenotypes, the ECT pain magnitude matching paradigm does not show
      adequate linear association with rating scale methods rendering the validity of
      the procedure as doubtful. ECT for sensory and pain threshold investigation,
      however, provides a method to objectively assess global sensory function in
      conjunction with sensory receptor specific bedside examination measures.

PMID- 24666410
TI  - Genetics of juvenile idiopathic arthritis.

PMID- 24666411
TI  - Special interest groups for 'sustainable rheumatology'.

PMID- 24666412
TI  - Direct cholangioscopy using an ultrathin endoscope for the diagnosis of
      hemobilia.

PMID- 24666413
TI  - Misconduct in research: a descriptive survey of attitudes, perceptions and
      associated factors in a developing country.
AB  - BACKGROUND: Misconduct in research tarnishes the reputation, credibility and
      integrity of research institutions. Studies on research or scientific misconduct
      are still novel in developing countries. In this study, we report on the
      attitudes, perceptions and factors related to the work environment thought to be
      associated with research misconduct in a group of researchers in Nigeria - a
      developing country. METHOD: A survey of researchers attending a scientific
      conference was done using an adapted Scientific Misconduct Questionnaire-Revised
      (SMQ-R). Initial descriptive analysis of individual items using frequencies and
      proportions for all quantitative data was performed. Thereafter, Likert scale
      responses were transformed into dichotomous responses. Fisher exact test was
      performed for associations as appropriate. A two-tailed p-value of less than 0.05
      was accepted as significant. RESULT: Half of the respondents (50.4%) were aware
      of a colleague who had committed misconduct, defined as "non-adherence to rules,
      regulations, guidelines, and commonly accepted professional codes or norms". Over
      88% of the researchers were concerned about the perceived amount of misconduct
      prevalent in their institution and 96.2% believed that one or more forms of
      scientific misconduct had occurred in their workplace. More than half (52.7%)
      rated the severity of penalties for scientific misconduct in their work
      environment as low. Furthermore  the majority (56.1%) were of the view that the
      chance of getting caught for scientific misconduct in their work environment was
      low. CONCLUSION: Researchers in Nigeria perceive that scientific misconduct is
      commonplace in their institutions, but are however worried about the negative
      effects of scientific misconduct on the credibility of scientific research. We
      recommend that researchers be empowered with the knowledge and virtues necessary
      for self-regulation that advance research integrity. Research institutions should
      however also step into their role of fostering a responsible research ethic and
      discouraging misconduct.

PMID- 24666415
TI  - Regioselective nucleophilic addition of organometallic reagents to 3-geminal
      bis(silyl) N-acyl pyridinium.
AB  - A regioselective nucleophilic addition to 3-geminal bis(silyl) N-acyl pyridinium
      has been described. Geminal bis(silane) shows contrasting roles that lead to
      different regioselectivities for the addition of different nucleophiles: its
      steric effect dominates to favor 1,6-addition of alkyl, vinyl, and aryl
      organometallic reagents; its directing effect dominates to favor 1,2-addition of
      less sterically demanding alkynyl Grignard reagents. 

PMID- 24666414
TI  - Primary small cell carcinoma of the esophagus: clinicopathological study of 44
      cases.
AB  - BACKGROUND: Primary small cell carcinoma of the esophagus (SCCE) is a highly
      aggressive disease characterized by early dissemination and poor prognosis.
      Because of the rarity of this disease, few previous studies have investigated the
      biomarkers associated with its prognosis. Leucine-rich repeat-containing G
      protein coupled receptor 5 (Lgr5) is a stem cell marker and a member of the
      canonical Wnt-signaling cascade. However, the clinical role of Lgr5 in SCCE
      remains unknown. METHODS: Tissue sections were obtained from 44 patients
      diagnosed with SCCE and expression of Lgr5 was examined by immunohistochemistry.
      The correlations between Lgr5 expression, and clinical parameters and prognostic
      significance were evaluated. RESULTS: Lgr5 was expressed in SCCE cancer tissues.
      High Lgr5 expression was significantly correlated with lymph node metastasis (p =
      0.003), late stage (p = 0.003) and unfavorable response to chemotherapy (p =
      0.013) according to RECIST 1.0 criteria. Patients with higher Lgr5 expression
      levels had shorter overall survival times than those with lower expression
      levels. CONCLUSIONS: These results demonstrated that overexpression of Lgr5 was
      significantly correlated with lymph node metastasis, tumor stage, and response to
      chemotherapy. Furthermore, high levels of Lgr5 expression appeared to be
      associated with poorer survival in patients with SCCE.

PMID- 24666416
TI  - Wogonin-enhanced reactive oxygen species-induced apoptosis and potentiated
      cytotoxic effects of chemotherapeutic agents by suppression Nrf2-mediated
      signaling in HepG2 cells.
AB  - Cancer cells, compared with normal cells, are under increased oxidative stress
      with higher level of reactive oxygen species (ROS). When exposed to environmental
      stresses such as ROS, NFE-related factor 2 (Nrf2) is the key to antioxidant
      response by transcriptionally activating various detoxification and antioxidant
      enzymes. Previously, we have shown that wogonin, a flavonoid isolated from the
      root of Scutellaria baicalensis Georgi, could reverse drug resistance in MCF
      7/DOX cells by blocking the translocation of Nrf2 into nucleus. However, the
      exact mechanism underlying the effect remains unclear. In this study, we observed
      that wogonin reduced the Nrf2 nuclear translocation, and therefore elevated the
      level of intracellular ROS to accomplish the purpose of killing malignant cells.
      Furthermore, the suppression of Nrf2 by wogonin can potentiate cytotoxic effects
      of chemotherapeutic agents in HepG2 cells. On one hand, down-regulation of Nrf2
      lead to reduction of cytoprotective effect by inducing phage II enzymes which
      sensitize cells to chemotherapeutic agents. On the other hand, inhibition of
      multidrug resistance-associated proteins (MRPs) by wogonin enhances the effective
      drug level in cancer cells and potentiates their chemotherapeutic effects.
      Finally, we found that the decrease of Nrf2 may be related to overexpression of
      p53. Using p53 siRNA to knock down the endogenous p53 expression, the levels of
      both c-myc and Nrf2 in nucleus increased when exposed to wogonin. The present
      study indicates that wogonin can be used in chemotherapy not only because of its
      own antitumor ability, but also due to the enhanced cytotoxic effects of
      chemotherapeutic agents.

PMID- 24666418
TI  - Simple and reusable picoinjector for liquid delivery via nanofluidics approach.
AB  - Precise control of sample volume is one of the most important functions in lab-on
      a-chip (LOC) systems, especially for chemical and biological reactions. The
      common approach used for liquid delivery involves the employment of capillaries
      and microstructures for generating a droplet which has a volume in the nanoliter
      or picoliter range. Here, we report a novel approach for constructing a
      picoinjector which is based on well-controlled electroosmotic (EO) flow to
      electrokinetically drive sample solutions. This picoinjector comprises an array
      of interconnected nanochannels for liquid delivery. Such technique for liquid
      delivery has the advantages of well-controlled sample volume and reusable
      nanofluidic chip, and it was reported for the first time. In the study of the
      pumping process for this picoinjector, the EO flow rate was determined by the
      intensity of the fluorescent probe. The influence of ion concentration in
      electrolyte solutions over the EO flow rate was also investigated and discussed.
      The application of this EO-driven picoinjector for chemical reactions was
      demonstrated by the reaction between Fluo-4 and calcium chloride with the
      reaction cycle controlled by the applied square waves of different duty cycles.
      The precision of our device can reach down to picoliter per second, which is much
      smaller than that of most existing technologies. This new approach, thus, opens
      further possibilities of adopting nanofluidics for well-controlled chemical
      reactions with particular applications in nanoparticle synthesis, bimolecular
      synthesis, drug delivery, and diagnostic testing. PACS: 85.85.+ j; 87.15.hj;
      82.39.Wj.

PMID- 24666419
TI  - Bilevel positive airway pressure for obstructive sleep apnea.
AB  - For most patients with obstructive sleep apnea syndrome (OSA), continuous
      positive airway pressure (CPAP) is an effective therapy. However, for a subset of
      individuals, CPAP is either not effective or is poorly tolerated. Bilevel
      positive airway pressure (BPAP) is potentially capable of treating OSA at a lower
      mean pressure than CPAP and can help augment ventilation via pressure support.
      This review summarizes the evidence for the use of BPAP in spontaneous mode in
      the initial treatment of patients with OSA and in those who are poorly compliant
      with CPAP therapy. It also examines evidence regarding use of BPAP in OSA with
      associated hypoventilation, such as in chronic obstructive pulmonary disease or
      severe obesity. Finally, current clinical guidelines that help determine which
      patients would be candidates for a BPAP device and how to manually titrate BPAP
      to determine the optimal settings to be prescribed are also discussed.

PMID- 24666417
TI  - Change in functional selectivity of morphine with the development of
      antinociceptive tolerance.
AB  - BACKGROUND AND PURPOSE: Opioids, such as morphine, are the most effective
      treatment for pain but their efficacy is diminished with the development of
      tolerance following repeated administration. Recently, we found that morphine
      activated ERK in opioid-tolerant but not in naive rats, suggesting that morphine
      activation of MU-opioid receptors is altered following repeated morphine
      administration. Here, we have tested the hypothesis that MU-opioid receptor
      activation of ERK in the ventrolateral periaqueductal gray (vlPAG) is dependent
      on dynamin, a protein implicated in receptor endocytosis. EXPERIMENTAL APPROACH:
      Rats were made tolerant to repeated microinjections of morphine into the vlPAG.
      The effects of dynamin on ERK activation and antinociception were assessed by
      microinjecting myristoylated dominant-negative dynamin peptide (Dyn-DN) or a
      scrambled control peptide into the vlPAG. Microinjection of a fluorescent
      dermorphin analogue (DERM-A594) into the vlPAG was used to monitor MU-opioid
      receptor internalization. KEY RESULTS: Morphine did not activate ERK and Dyn-DN
      administration had no effect on morphine-induced antinociception in saline
      pretreated rats. In contrast, morphine-induced ERK activation in morphine
      pretreated rats that was blocked by Dyn-DN administration. Dyn-DN also inhibited
      morphine antinociception. Finally, morphine reduced DERM-A594 internalization
      only in morphine-tolerant rats indicating that MU-opioid receptors were
      internalized and unavailable to bind DERM-A594. CONCLUSIONS AND IMPLICATIONS:
      Repeated morphine administration increased MU-opioid receptor activation of ERK
      signalling via a dynamin-dependent mechanism. These results demonstrate that the
      balance of agonist signalling to G-protein and dynamin-dependent pathways is
      altered, effectively changing the functional selectivity of the agonist-receptor
      complex. LINKED ARTICLES: This article is part of a themed section on Opioids:
      New Pathways to Functional Selectivity. To view the other articles in this
      section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

PMID- 24666421
TI  - Transient residence of a seropositive organ is sufficient to transfer human
      cytomegalovirus to a seronegative recipient.
AB  - Many aspects of the pathogenesis of human cytomegalovirus (HCMV) infection in
      liver transplantation remain unclear. This study examined the transfer of HCMV
      from the transient residence of a seropositive organ in seronegative recipients.
      All subjects receiving >1 orthotopic liver transplant (LT) were identified from
      an LT database. The patients of interest were HCMV-seronegative LT recipients who
      received their first organ from a seropositive donor, and subsequently a second
      LT from a seronegative donor within 30 days. Of 98 patients identified, 6 met
      these criteria and 4 developed viremia; in 2 cases, after the seropositive organ
      was in situ for 28 and 109 h. We can therefore conclude that 28 h is sufficient
      to allow HCMV to transmit, but the minimum time has not yet been defined.

PMID- 24666420
TI  - The evolution of nursing in Australian general practice: a comparative analysis
      of workforce surveys ten years on.
AB  - BACKGROUND: Nursing in Australian general practice has grown rapidly over the
      last decade in response to government initiatives to strengthen primary care.
      There are limited data about how this expansion has impacted on the nursing role,
      scope of practice and workforce characteristics. This study aimed to describe the
      current demographic and employment characteristics of Australian nurses working
      in general practice and explore trends in their role over time. METHODS: In the
      nascence of the expansion of the role of nurses in Australian general practice
      (2003-2004) a national survey was undertaken to describe nurse demographics,
      clinical roles and competencies. This survey was repeated in 2009-2010 and
      comparative analysis of the datasets undertaken to explore workforce changes over
      time. RESULTS: Two hundred eighty four nurses employed in general practice
      completed the first survey (2003/04) and 235 completed the second survey
      (2009/10). Significantly more participants in Study 2 were undertaking follow-up
      of pathology results, physical assessment and disease specific health education.
      There was also a statistically significant increase in the participants who felt
      that further education/training would augment their confidence in all clinical
      tasks (p < 0.001). Whilst the impact of legal implications as a barrier to the
      nurses' role in general practice decreased between the two time points, more
      participants perceived lack of space, job descriptions, confidence to negotiate
      with general practitioners and personal desire to enhance their role as barriers.
      Access to education and training as a facilitator to nursing role expansion
      increased between the two studies. The level of optimism of participants for the
      future of the nurses' role in general practice was slightly decreased over time.
      CONCLUSIONS: This study has identified that some of the structural barriers to
      nursing in Australian general practice have been addressed over time. However, it
      also identifies continuing barriers that impact practice nurse role development.
      Understanding and addressing these issues is vital to optimise the effectiveness
      of the primary care nursing workforce.

PMID- 24666422
TI  - Reduction of the water wettability of cellulose film through controlled
      heterogeneous modification.
AB  - A facile method had been applied to introduce hydrophobic properties to cellulose
      materials by incorporation of polyurethane acrylate (PUA) prepolymers into the
      porous structured cellulose matrix through dip-coating; then, PUA prepolymers
      were cured around interconnected cellulose fibers under UV light, encapsulating a
      cellulose matrix with a hydrophobic polymer shell. The characterization of the
      composite films confirmed the success of the heterogeneous modification, and the
      chemical structure of the cellulose matrix was preserved. The composite films
      integrated the merits of cellulose and PUA resin, but the highly hydrophilic
      behavior of cellulose has been reduced. Contact angle measurements with water
      demonstrated that the composite films had obvious hydrophobic properties and an
      obvious reduction in the water uptake and the permeability toward water vapor gas
      at different relative humidity was also observed. The transmittance of the
      composite films at 550 nm was about 85%. The thermal and mechanical properties of
      the composite films were improved when compared with that of PUA resin. The
      obtained composite based on cellulose and UV curing technology was a good choice
      for the development of biomass materials with modified surface properties. 

PMID- 24666424
TI  - Inhibition of polyamine formation antagonizes vascular smooth muscle cell
      proliferation and preserves the contractile phenotype.
AB  - The polyamines putrescine, spermidine and spermine play essential roles in cell
      proliferation and migration, two processes involved in the development of
      vascular disease. Thus, intervention with polyamine formation may represent a way
      to inhibit unwanted vascular smooth muscle cell (VSMC) proliferation. The aim of
      the present study was to assess the importance of polyamines for VSMC
      proliferation and vascular contractility. The rate-limiting step in polyamine
      biosynthesis is catalysed by ornithine decarboxylase (ODC). Treatment with alpha
      difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, reduced DNA
      synthesis in primary rat VSMCs in a concentration-dependent manner with an IC50
      value of 100 MUM. Moreover, DFMO reduced VSMC migration assessed in a scratch
      assay. The DFMO-induced attenuation of VSMC proliferation was associated with
      lowered cellular amount of polyamines. The antiproliferative effect of DFMO was
      specific because supplementation with polyamines reversed the effect of DFMO on
      proliferation and normalized cellular polyamine levels. Isometric force
      recordings in cultured rat tail artery rings showed that DFMO counteracts the
      decrease in contractility caused by culture with foetal bovine serum as growth
      stimulant. We conclude that inhibition of polyamine synthesis by DFMO may limit
      the first wave of cell proliferation and migration, which occurs in the acute
      phase after vascular injury. Besides its antiproliferative effect, DFMO may
      prevent loss of the smooth muscle contractile phenotype in vascular injury. 

PMID- 24666423
TI  - Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced
      murine lupus-like model.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide exhibiting
      anti-inflammatory activity in experimental models of autoimmune diseases.
      However, no studies thus far have examined the effects of alpha-MSH on systemic
      lupus erythematosus (SLE). This study aimed to determine the effects of an alpha
      MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in
      which lupus was induced by pristane. Groups of lupus animals were treated daily
      with the alpha-MSH analogue [Nle4, DPhe7]-alpha-MSH (NDP-MSH) (1.25 mg/kg)
      injected intraperitoneally or saline for 180 days. Normal animals comprised the
      control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti
      nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was
      assessed by proteinuria and histopathological lesion. Glomerular levels of IgG,
      alpha-smooth muscle actin (alpha-SMA), inducible nitric oxide synthase (iNOS),
      C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and
      alpha-MSH was estimated by immunohistochemistry. When compared with normal
      controls, lupus animals exhibited increased arthritis, IgG levels, ANA,
      interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together
      with glomerular expression of alpha-SMA and iNOS. Glomerular expression of MCR1
      was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70%
      and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus,
      NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits,
      and expression levels of alpha-SMA, iNOS and CRF were also all decreased. Taken
      together, our results suggest for the first time that alpha-MSH treatment
      improves several parameters of SLE disease activity in mice, and indicate that
      this hormone is an interesting potential future treatment option.

PMID- 24666425
TI  - Formation of community-based hypertension practice networks: success, obstacles,
      and lessons learned.
AB  - Community-based practice networks for research and improving the quality of care
      are growing in size and number but have variable success rates. In this paper,
      the authors review recent efforts to initiate a community-based hypertension
      network modeled after the successful Outpatient Quality Improvement Network
      (O'QUIN) project, located at the Medical University of South Carolina. Key
      lessons learned and new directions to be explored are highlighted. 

PMID- 24666426
TI  - Properties of 4 Hz stimulation-induced parallel fiber-Purkinje cell presynaptic
      long-term plasticity in mouse cerebellar cortex in vivo.
AB  - Cerebellar parallel fiber-Purkinje cell (PF-PC) long-term synaptic plasticity is
      important for the formation and stability of cerebellar neuronal circuits, and
      provides substrates for motor learning and memory. We previously reported both
      presynaptic long-term potentiation (LTP) and long-term depression (LTD) in
      cerebellar PF-PC synapses in vitro. However, the expression and mechanisms of
      cerebellar PF-PC synaptic plasticity in the cerebellar cortex in vivo are poorly
      understood. In the present study, we studied the properties of 4 Hz stimulation
      induced PF-PC presynaptic long-term plasticity using in vivo the whole-cell patch
      clamp recording technique and pharmacological methods in urethane-anesthetised
      mice. Our results demonstrated that 4 Hz PF stimulation induced presynaptic LTD
      of PF-PC synaptic transmission in the intact cerebellar cortex in living mice.
      The PF-PC presynaptic LTD was attenuated by either the N-methyl-D-aspartate
      receptor antagonist, D-aminophosphonovaleric acid, or the group 1 metabotropic
      glutamate receptor antagonist, JNJ16259685, and was abolished by combined D
      aminophosphonovaleric acid and JNJ16259685, but enhanced by inhibition of nitric
      oxide synthase. Blockade of cannabinoid type 1 receptor activity abolished the PF
      PC LTD and revealed a presynaptic PF-PC LTP. These data indicate that both
      endocannabinoids and nitric oxide synthase are involved in the 4 Hz stimulation
      induced PF-PC presynaptic plasticity, but the endocannabinoid-dependent PF-PC
      presynaptic LTD masked the nitric oxide-mediated PF-PC presynaptic LTP in the
      cerebellar cortex in urethane-anesthetised mice. 

PMID- 24666427
TI  - A new method for the comparison of 1H NMR predictors based on tree-similarity of
      spectra.
AB  - A methodology based on spectral similarity is presented that allows to compare
      NMR predictors without the recourse to assigned experimental spectra, thereby
      making the task of benchmarking NMR predictors less tedious, faster, and less
      prone to human error. This approach was used to compare four popular NMR
      predictors using a dataset of 1000 molecules and their corresponding experimental
      spectra. The results found were consistent with those obtained by directly
      comparing deviations between predicted and experimental shifts. 

PMID- 24666428
TI  - Pharmacokinetics of buprenorphine following intravenous and intramuscular
      administration in male rhesus macaques (Macaca mulatta).
AB  - This study reports the pharmacokinetics of buprenorphine in conscious rhesus
      macaques (Macaca mulatta) after intravenous (i.v.) and intramuscular (i.m.)
      administration. Four healthy, opioid-naive, socially housed, adult male macaques
      were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus
      or intramuscularly on separate occasions. Blood samples were collected prior to,
      and up to 24 h, postadministration. Serum buprenorphine concentrations were
      analyzed with liquid chromatography-mass spectrometry. Noncompartmental
      pharmacokinetic analysis was performed with commercially available software. Mean
      residence time in the i.v. study as compared to the i.m. study was 177 (159-189)
      vs. 185 (174-214) min, respectively [median (range)]. In the i.v. study,
      concentration back-extrapolated to time zero was found to be 33.0 (16.8-57.0)
      ng/mL [median (range)]. On the other hand, the maximum serum concentration found
      in the i.m. study was 11.8 (6.30-14.8) ng/mL [median (range)]. Rhesus macaques
      maintained concentrations >0.10 ng/mL for over 24 h in the i.v. study and over 12
      h in the i.m. study. Bioavailability was found to be 68.1 (59.3-71.2)% [median
      (range)]. No significant adverse effects were observed in the monkeys at the 0.03
      mg/kg dose of buprenorphine during either study. 

PMID- 24666429
TI  - An autologous bone marrow mesenchymal stem cell-derived extracellular matrix
      scaffold applied with bone marrow stimulation for cartilage repair.
AB  - PURPOSE: It is well known that implanting a bioactive scaffold into a cartilage
      defect site can enhance cartilage repair after bone marrow stimulation (BMS).
      However, most of the current scaffolds are derived from xenogenous tissue and/or
      artificial polymers. The implantation of these scaffolds adds risks of pathogen
      transmission, undesirable inflammation, and other immunological reactions, as
      well as ethical issues in clinical practice. The current study was undertaken to
      evaluate the effectiveness of implanting autologous bone marrow mesenchymal stem
      cell-derived extracellular matrix (aBMSC-dECM) scaffolds after BMS for cartilage
      repair. METHODS: Full osteochondral defects were performed on the trochlear
      groove of both knees in 24 rabbits. One group underwent BMS only in the right
      knee (the BMS group), and the other group was treated by implantation of the
      aBMSC-dECM scaffold after BMS in the left knee (the aBMSC-dECM scaffold group).
      RESULTS: Better repair of cartilage defects was observed in the aBMSC-dECM
      scaffold group than in the BMS group according to gross observation, histological
      assessments, immunohistochemistry, and chemical assay. The glycosaminoglycan and
      DNA content, the distribution of proteoglycan, and the distribution and
      arrangement of type II and I collagen fibers in the repaired tissue in the aBMSC
      dECM scaffold group at 12 weeks after surgery were similar to that surrounding
      normal hyaline cartilage. CONCLUSIONS: Implanting aBMSC-dECM scaffolds can
      enhance the therapeutic effect of BMS on articular cartilage repair, and this
      combination treatment is a potential method for successful articular cartilage
      repair.

PMID- 24666430
TI  - Tubular urinary biomarkers do not identify aetiology of acute kidney injury in
      kidney transplant recipients.
AB  - AIM: To evaluate the performance of urinary neutrophil gelatinase-associated
      lipocalin (uNGAL), kidney injury molecule, interleukin-18 and heat shock protein
      72 for differential diagnosis between causes of acute kidney injury in kidney
      transplant recipients, especially immunological rejection. PATIENTS AND METHODS:
      We measured these biomarkers in 67 kidney transplant recipients with acute kidney
      injury according to the RIFLE criteria. RESULTS: There were no statistical
      differences in biomarkers between kidney transplant recipients with immunological
      rejection (n = 20), pre-renal causes (n = 20) and other AKI causes (n = 27). Only
      the uNGAL level relative to urinary creatinine (uNGAL/uCr) for immunological
      rejection was different in comparison with others (P < 0.001); a cut-off of 59
      MUg/g of uNGAL/uCr had a sensitivity and specificity of 60% and 58% respectively
      (area under the curve in receiver-operating characteristic curve, 0.65). The
      other biomarkers were not useful in differentiating the causes of acute kidney
      injury. CONCLUSION: The biomarkers tested are not useful in identifying
      immunological rejection as cause of acute kidney injury in kidney transplant
      recipients.

PMID- 24666431
TI  - Decisions that hasten death: double effect and the experiences of physicians in
      Australia.
AB  - BACKGROUND: In Australian end-of-life care, practicing euthanasia or physician
      assisted suicide is illegal. Despite this, death hastening practices are common
      across medical settings. Practices can be clandestine or overt but in many
      instances physicians are forced to seek protection behind ambiguous medico-legal
      imperatives such as the Principle of Double Effect. Moreover, the way they
      conceptualise and experience such practices is inconsistent. To complement the
      available statistical data, the purpose of this study was to understand the
      reasoning behind how and why physicians in Australia will hasten death. METHOD: A
      qualitative investigation was focused on palliative and critical/acute settings.
      A thematic analysis was conducted on semi-structured in-depth interviews with 13
      specialist physicians. Attention was given to eliciting meanings and experiences
      in Australian end-of-life care. RESULTS: Highlighting the importance of a
      multidimensional approach, physicians negotiated multiple influences when death
      was regarded as hastened. The way they understood and experienced end-of-life
      care practices were affected by politico-religious and cultural influences,
      medico-legal imperatives, and personal values and beliefs. Interpersonal and
      intrapsychic aspects further emphasised the emotional and psychological
      investment physicians have with patients and others. In most cases death occurred
      as a result of treating suffering, and sometimes to fulfil the wishes of patients
      and others who requested death. Experience was especially subject to the efficacy
      with which physicians negotiated complex but context-specific situations, and was
      reflective of how they considered a good death. Although many were compelled to
      draw on the Principle of Double Effect, every physician reported its inadequacy
      as a medico-legal guideline. CONCLUSIONS: The Principle of Double Effect, as a
      simplistic and generalised guideline, was identified as a convenient mechanism to
      protect physicians who inadvertently or intentionally hastened death. But its
      narrow focus on the physician's intent illuminated how easily it may be
      manipulated, thus impairing transparency and a physician's capacity for honesty.
      It is suggested the concept of "force majeure" be examined for its applicability
      in Australian medical end-of-life law where, consistent with a multidimensional
      and complex world, a physician's motivations can also be understood in terms of
      the emotional and psychological pressures they face in situations that hasten
      death.

PMID- 24666432
TI  - Screening of atmospheric short- and medium-chain chlorinated paraffins in India
      and Pakistan using polyurethane foam based passive air sampler.
AB  - Production and use of chlorinated paraffins (CPs) have been increasing in India.
      Distribution of CPs in the area and vicinity have become a great concern due to
      their persistency and toxicity. Polyurethane foam based passive air samplers (PUF
      PAS) was deployed in order to screen the presence of short- and medium- chain
      chlorinated paraffins (SCCPs and MCCPs) in the outdoor atmosphere at many sites
      in India (in winter 2006) and Pakistan (in winter 2011). Concentrations of SCCPs
      and MCCPs ranged from not detected (ND) to 47.4 and 0 to 38.2 ng m(-3) with means
      of 8.11 and 4.83 ng m(-3), respectively. Indian concentrations showed higher
      average levels of both SCCPs and MCCPs India (10.2 ng m(-3) and 3.62 ng m(-3)than
      the samples from Pakistan (5.13 ng m(-3) and 4.21 ng m(-3)). Relative abundance
      patterns of carbon number are C10 > C11 > C12 ~ C13 for SCCPs and C14 > C15 > C16
      C17 for MCCP with similarity to the profiles of samples from China, the biggest
      CPs producer in the world. Principal Component Analysis suggested that detected
      SCCPs and MCCPs in this study originated from the same emission source. 

PMID- 24666433
TI  - Aloe vera: an in vitro study of effects on corneal wound closure and collagenase
      activity.
AB  - PURPOSE: To evaluate the in vitro effects of an aloe vera solution on (i) the
      viability and wound healing response of corneal cells and (ii) the ability to
      alter collagenase and gelatinase activities. METHODS: Primary cultures of corneal
      epithelial cells and fibroblasts were prepared from grossly normal enucleated
      canine globes and treated with an aloe solution (doses ranging from 0.0-2 mg/mL).
      Cellular viability was evaluated using a colorimetric assay. A corneal wound
      healing model was used to quantify cellular ingrowth across a defect made on the
      confluent surface. Anticollagenase and antigelatinase activities were evaluated
      by incubating a bacterial collagenase/gelatinase with aloe solution (doses
      ranging from 0.0-500 MUg/mL) and comparing outcome measures to a general
      metalloproteinase inhibitor, 1, 10-phenanthroline, and canine serum (doses
      ranging from 0.0-100%). RESULTS: None of the concentrations of aloe solution
      tested significantly affected the viability of corneal epithelial cells or
      fibroblasts. Concentrations <=175 MUg/mL slightly accelerated corneal epithelial
      cell wound closure; this change was not significant. Concentrations >=175 MUg/mL
      significantly (P <= 0.001) slowed the rate of corneal fibroblast wound closure,
      while aloe concentrations <175 MUg/mL did not significantly alter fibroblast
      wound closure. Aloe solution did not alter the ability for collagenase to degrade
      gelatin or collagen Type I but increased the ability for collagenase to degrade
      Type IV collagen. CONCLUSIONS: Although additional experiments are required,
      lower concentrations of aloe solution may be beneficial in healing of superficial
      corneal wounds to help decrease fibrosis and speed epithelialization. An increase
      in collagenase activity with aloe vera warrants further testing before
      considering in vivo studies.

PMID- 24666434
TI  - Rheumatoid factor in idiotypic regulation of autoimmunity.
AB  - AIM: Rheumatoid factor (RF) is known to be heterogeneous, and RFs detected by
      various methods exhibit different characteristics. In addition to interacting
      with the Fc region of immunoglobulin G (IgG), certain RFs are able to recognize
      idiotypes of antibodies. Given the important role of idiotypic interactions in
      regulating autoimmunity, we hypothesize that RF is involved in regulation of
      lymphocyte activity against autoimmune disease-inducing antigens via idiotype
      anti-idiotype interactions with these lymphocytes. METHOD: RF level and the
      existence of idiotype-anti-idiotype interactions between RF and antibodies to
      autoimmunity-inducing antigens were studied in rats resistant and sensitive to
      collagen-induced arthritis, encephalomyelitis and atherosclerosis. RF was assayed
      by agglutination of tanned IgG-loaded erythrocytes. RESULTS: Rat resistance to
      autoimmune disease is associated with high RF production during the initiation of
      the immune response, and a low RF level during this period may be a preclinical
      marker of experimental autoimmune disease manifestation. RF-containing sera
      compete with an antigen if the RF-containing sera were obtained from rats
      immunized with that antigen, and they non-specifically inhibit binding of
      different antigen-antibody pairs. This suggests that RFs are anti-idiotypic
      antibodies that carry two kinds of paratopes: a particular paratope that
      recognizes the antigen-binding sites of antibodies, and a shared paratope that
      serves to recognize the recurrent idiotype on antibodies. Antigenic epitopes for
      the shared RF paratope can be created in the hinge region of Fc fragments of
      homologous IgG. CONCLUSION: RF detected by agglutination of tanned IgG-loaded
      erythrocytes is involved in negative idiotypic regulation of lymphocytes specific
      to autoimmunity-inducing antigens.

PMID- 24666435
TI  - Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA
      silencing of metabolic enzymes.
AB  - BACKGROUND: Cancer cells may undergo metabolic adaptations that support their
      growth as well as drug resistance properties. The purpose of this study is to
      test if oral cancer cells can overcome the metabolic defects introduced by using
      small interfering RNA (siRNA) to knock down their expression of important
      metabolic enzymes. METHODS: UM1 and UM2 oral cancer cells were transfected with
      siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western
      blotting was used to confirm the knockdown. Cellular uptake of glucose and
      glutamine and production of lactate were compared between the cancer cells with
      either TKT or AK2 knockdown and those transfected with control siRNA. Statistical
      analysis was performed with student T-test. RESULTS: Despite the defect in the
      pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or
      UM2 cells utilized more glucose and glutamine and secreted a significantly higher
      amount of lactate than the cells transferred with control siRNA. We also
      demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and
      UM2 cells but similarly led to an increased uptake of glucose/glutamine and
      production of lactate by the UM1 or UM2 cells survived from siRNA silencing of
      AK2. CONCLUSIONS: Our results indicate that the metabolic defects introduced by
      siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative
      feedback metabolic mechanisms, suggesting that cancer cells may overcome single
      defective pathways through secondary metabolic network adaptations. The highly
      robust nature of oral cancer cell metabolism implies that a systematic medical
      approach targeting multiple metabolic pathways may be needed to accomplish the
      continued improvement of cancer treatment.

PMID- 24666436
TI  - Graphene-enhanced visible-light photocatalysis of large-sized CdS particles for
      wastewater treatment.
AB  - The hybrid composites of graphene decorated by large-sized CdS particles (G/M
      CdS) were prepared by a one-pot solvothermal route in which the reduction of
      graphite oxide into graphene was accompanied by the generation of microsized CdS
      particles. The structure and composition of the obtained nanocomposites were
      studied by means of X-ray diffraction, scanning electron microscopy, and
      transmission electron microscopy. The CdS particles with the average sizes of
      approximately 640 nm were formed on graphene sheets. The as-prepared composite
      was used as adsorbent to remove dye from wastewater using the organic dye
      Rhodamine B as the adsorbate. The G/M-CdS composite reveals a high
      photodegradation rate under visible light irradiation. Our results demonstrate
      that the G/M-CdS is very promising for removing organic dyes from wastewater. 

PMID- 24666439
TI  - Platelet-rich plasma and bone defect healing.
AB  - On activation, platelets secrete an array of growth factors that contribute to
      bone regeneration. Combining platelet-rich plasma (PRP) with bone graft
      substitutes has the potential to reduce or replace the reliance on autografts.
      Lack of standardization and improper use may contribute to the conflicting
      outcomes reported within both preclinical and clinical investigations using PRP.
      This study investigates the effect of PRP dose on bone augmentation. Eighty
      critical-sized defects were created in the cancellous bone of the medial proximal
      tibia and the distal femur of 20 five-year-old female sheep. The defects were
      treated with three doses of an autologous thrombin-activated PRP combined with a
      biphasic calcium phosphate (BCP) or autograft and empty defects. Radiography,
      micro-computed tomography, histology, histomorphometry, and fluorochrome bone
      labels were examined at 4 weeks. The empty defects did not spontaneously heal.
      The highest dose of PRP treatment had a significantly greater micro-CT bone
      volume/total volume compared with the BCP alone (PRP: 30.6%+/-1.8%; BCP: 24.5%+/
      0.1%). All doses of PRP treatment were significantly greater than the BCP alone
      for histomorphometric new bone area (PRP: 14.5%+/-1.3%; BCP: 9.7%+/-1.5%) and
      bone ingrowth depth (PRP: 2288+/-210 MUm; BCP:1151+/-268 MUm). From week 2
      onward, PRP had a significant effect on the weekly bone ingrowth compared with
      BCP; however, autografts had the highest amount of weekly fluorescent bone
      labeling. PRP induces new bone formation with a dose-dependent response at 4
      weeks when used with a BCP in sheep. 

PMID- 24666437
TI  - Age-associated Epstein-Barr virus-specific T cell responses in seropositive
      healthy adults.
AB  - Epstein-Barr virus (EBV) is present in 95% of the world's adult population. The
      immune response participates in immune vigilance and persistent infection
      control, and this condition is maintained by both a good quality (functionality)
      and quantity of specific T cells throughout life. In the present study, we
      evaluated EBV-specific CD4(+) and CD8(+) T lymphocyte responses in seropositive
      healthy individuals younger and older than 50 years of age. The assessment
      comprised the frequency, phenotype, functionality and clonotypic distribution of
      T lymphocytes. We found that in both age groups a similar EBV-specific T cell
      response was found, with overlapping numbers of tumour necrosis factor (TNF)
      alpha(+) T lymphocytes (CD4(+) and CD8(+)) within the memory and effector cell
      compartments, in addition to monofunctional and multi-functional T cells
      producing interleukin (IL)-2 and/or interferon (IFN)-gamma. However, individuals
      aged more than 50 years showed significantly higher frequencies of IL-2-producing
      CD4(+) T lymphocytes in association with greater production of soluble IFN-gamma,
      TNF-alpha and IL-6 than subjects younger than 50 years. A polyclonal T cell
      receptor (TCR)-variable beta region (Vbeta) repertoire exists in both age groups
      under basal conditions and in response to EBV; the major TCR families found in
      TNF-alpha(+) /CD4(+) T lymphocytes were Vbeta1, Vbeta2, Vbeta17 and Vbeta22 in
      both age groups, and the major TCR family in TNF-alpha(+) /CD8(+) T cells was
      Vbeta13.1 for individuals younger than 50 years and Vbeta9 for individuals aged
      more than 50 years. Our findings suggest that the EBV-specific T cell response
      (using a polyclonal stimulation model) is distributed throughout several T cell
      differentiation compartments in an age-independent manner and includes both
      monofunctional and multi-functional T lymphocytes.

PMID- 24666440
TI  - High definition video teaching module for learning neck dissection.
AB  - INTRODUCTION: Video teaching modules are proven effective tools for enhancing
      student competencies and technical skills in the operating room. Integration into
      post-graduate surgical curricula, however, continues to pose a challenge in
      modern surgical education. To date, video teaching modules for neck dissection
      have yet to be described in the literature. PURPOSE: To develop and validate an
      HD video-based teaching module (HDVM) to help instruct post-graduate
      otolaryngology trainees in performing neck dissection. METHODS: This prospective
      study included 6 intermediate to senior otolaryngology residents. All consented
      subjects first performed a control selective neck dissection. Subjects were then
      exposed to the video teaching module. Following a washout period, a repeat
      procedure was performed. Recordings of the both sets of neck dissections were de
      identified and reviewed by an independent evaluator and scored using the
      Observational Clinical Human Reliability Assessment (OCHRA) system. RESULTS: In
      total 91 surgical errors were made prior to the HDVM and 41 after exposure,
      representing a 55% decrease in error occurrence. The two groups were found to be
      significantly different. Similarly, 66 and 24 staff takeover events occurred pre
      and post HDVM exposure, respectively, representing a statistically significant
      64% decrease. CONCLUSION: HDVM is a useful adjunct to classical surgical
      training. Residents performed significantly less errors following exposure to the
      HD-video module. Similarly, significantly less staff takeover events occurred
      following exposure to the HDVM.

PMID- 24666438
TI  - Intervention to improve social and family support for caregivers of dependent
      patients: ICIAS study protocol.
AB  - BACKGROUND: Despite the existence of formal professional support services,
      informal support (mainly family members) continues to be the main source of
      eldercare, especially for those who are dependent or disabled. Professionals on
      the primary health care are the ideal choice to educate, provide psychological
      support, and help to mobilize social resources available to the informal
      caregiver.Controversy remains concerning the efficiency of multiple
      interventions, taking a holistic approach to both the patient and caregiver, and
      optimum utilization of the available community resources. .For this reason our
      goal is to assess whether an intervention designed to improve the social support
      for caregivers effectively decreases caregivers burden and improves their quality
      of life. METHODS/DESIGN:  DESIGN: CONTROLled, multicentre, community intervention
      trial, with patients and their caregivers randomized to the intervention or
      control group according to their assigned Primary Health Care Team (PHCT). STUDY
      AREA: Primary Health Care network (9 PHCTs). STUDY PARTICIPANTS: Primary informal
      caregivers of patients receiving home health care from participating PHCTs.
      SAMPLE: Required sample size is 282 caregivers (141 from PHCTs randomized to the
      intervention group and 141 from PHCTs randomized to the control group.
      INTERVENTION: a) PHCT professionals: standardized training to implement
      caregivers intervention. b) Caregivers: 1 individualized counselling session, 1
      family session, and 4 educational group sessions conducted by participating PHCT
      professionals; in addition to usual home health care visits, periodic telephone
      follow-up contact and unlimited telephone support. CONTROL: Caregivers and
      dependent patients: usual home health care, consisting of bimonthly scheduled
      visits, follow-up as needed, and additional attention upon request.Data
      analysisDependent variables: Caregiver burden (short-form Zarit test),
      caregivers' social support (Medical Outcomes Study), and caregivers' reported
      quality of life (SF-12)INDEPENDENT VARIABLES: a) Caregiver: sociodemographic
      data, Goldberg Scale, Apgar family questionnaire, Holmes and Rahe Psychosocial
      Stress Scale, number of chronic diseases. b) Dependent patient: sociodemographic
      data, level of dependency (Barthel Index), cognitive impairment (Pfeiffer test).
      DISCUSSION: If the intervention intended to improve social and family support is
      effective in reducing the burden on primary informal caregivers of dependent
      patients, this model can be readily applied throughout usual PHCT clinical
      practice. TRIAL REGISTRATION: Clinical trials registrar: NCT02065427.

PMID- 24666441
TI  - Education through recreation.

PMID- 24666443
TI  - Prevention of delirium in trauma patients: are we giving thiamine prophylaxis a
      fair chance?
AB  - BACKGROUND: Delirium is associated with increased morbidity and mortality in
      injured patients. Wernicke encephalopathy (WE) is delirium linked to malnutrition
      and chronic alcoholism. It is prevented with administration of thiamine. Our
      primary goal was to evaluate current blood alcohol level (BAL) testing and
      thiamine prophylaxis in severely injured patients. METHODS: We retrospectively
      reviewed the cases of 1000 consecutive severely injured patients admitted to
      hospital between Mar. 1, 2009, and Dec. 31, 2009. We used the patients' medical
      records and the Alberta Trauma Registry. RESULTS: Among 1000 patients (mean age
      48 yr, male sex 70%, mean injury severity score 23, mortality 10%), 627 underwent
      BAL testing at admission; 221 (35%) had a BAL greater than 0 mmol/L, and 189
      (30%) had a BAL above the legal limit of 17.4 mmol/L. The mean positive BAL was
      41.9 mmol/L. More than 4% had a known history of alcohol abuse. More patients
      were assaulted (20% v. 9%) or hit by motor vehicles (10% v. 6%) when intoxicated
      (both p < 0.05). Most injuries occurred after falls (37%) and motor vehicle
      collisions (33%). Overall, 17% of patients received thiamine prophylaxis. Of the
      221 patients with elevated BAL, 44% received thiamine prophylaxis. Of those with
      a history of alcohol abuse, 77% received thiamine prophylaxis. CONCLUSION:
      Despite the strong link between alcohol abuse, trauma and WE, more than one-third
      of patients were not screened for alcohol use. Furthermore, a minority of
      intoxicated patients received adequate prophylaxis against WE. Given the low risk
      and cost of BAL testing and thiamine prophylaxis and the high cost of delirium,
      standard protocols for prophylaxis are essential.

PMID- 24666444
TI  - Is there any evidence of a "July effect" in patients undergoing major cancer
      surgery?
AB  - BACKGROUND: The "July effect" refers to the phenomenon of adverse impacts on
      patient care arising from the changeover in medical staff that takes place during
      this month at academic medical centres in North America. There has been some
      evidence supporting the presence of the July effect, including data from surgical
      specialties. Uniformity of care, regardless of time of year, is required for
      patients undergoing major cancer surgery. We therefore sought to perform a
      population-level assessment for the presence of a July effect in this field.
      METHODS: We used the Nationwide Inpatient Sample to abstract data on patients
      undergoing 1 of 8 major cancer surgeries at academic medical centres between Jan.
      1, 1999, and Dec. 30, 2009. The primary outcomes examined were postoperative
      complications and in-hospital mortality. Univariate analyses and subsequently
      multivariate analyses, controlling for patient and hospital characteristics, were
      performed to identify whether the time of surgery was an independent predictor of
      outcome after major cancer surgery. RESULTS: On univariate analysis, the overall
      postoperative complication rate, as well as genitourinary and hematologic
      complications specifically, was higher in July than the rest of the year.
      However, on multivariate analysis, only hematologic complications were
      significantly higher in July, with no difference in overall postoperative
      complication rate or in-hospital mortality for all 8 surgeries considered
      separately or together. CONCLUSION: On the whole, the data confirm an absence of
      a July effect in patients undergoing major cancer surgery.

PMID- 24666445
TI  - Emotional intelligence in orthopedic surgery residents.
AB  - BACKGROUND: Emotional intelligence (EI) is the ability to understand and manage
      emotions in oneself and others. It was originally popularized in the business
      literature as a key attribute for success that was distinct from cognitive
      intelligence. Increasing focus is being placed on EI in medicine to improve
      clinical and academic performance. Despite the proposed benefits, to our
      knowledge, there have been no previous studies on the role of EI in orthopedic
      surgery. We evaluated baseline data on EI in a cohort of orthopedic surgery
      residents. METHODS: We asked all orthopedic surgery residents at a single
      institution to complete an electronic version of the Mayer-Salovey-Caruso
      Emotional Intelligence Test (MSCEIT). We used completed questionnaires to
      calculate total EI scores and 4 branch scores. Data were analyzed according to a
      priori cutoff values to determine the proportion of residents who were considered
      competent on the test. Data were also analyzed for possible associations with
      age, sex, race and level of training. RESULTS: Thirty-nine residents (100%)
      completed the MSCEIT. The mean total EI score was 86 (maximum score 145). Only 4
      (10%) respondents demonstrated competence in EI. Junior residents (p = 0.026),
      Caucasian residents (p = 0.009) and those younger than 30 years (p = 0.008) had
      significantly higher EI scores. CONCLUSION: Our findings suggest that orthopedic
      residents score low on EI based on the MSCEIT. Optimizing resident competency in
      noncognitive skills may be enhanced by dedicated EI education, training and
      testing.

PMID- 24666446
TI  - A patient-centred approach toward surgical wait times for colon cancer: a
      population-based analysis.
AB  - BACKGROUND: Administrative wait times reflect the time from the decision to treat
      until surgery; however, this does not reflect the total time a patient actually
      waits for treatment. Several factors may prolong the wait for colon cancer
      surgery. We sought to analyze the time from the date of surgical consultation to
      the date of surgery and any events within this time frame that may extend wait
      times. METHODS: We retrospectively reviewed the cases of all adult patients in
      Ontario aged 18-80 years with diagnosed colon cancer who did not receive
      neoadjuvant therapy and underwent resection electively between Jan. 1, 2002, and
      Dec. 31, 2009. Wait times were measured from the date of surgical consultation to
      the date of surgery. We chose a wait time of 28 days, reflecting local
      administrative targets, as a comparative benchmark. We performed univariate and
      multivariate analyses to identify variables contributing to a waits longer than
      28 days. Variables were analyzed in continuous linear and logistic regression
      models. RESULTS: We included 10 223 patients in our study. The median wait time
      from initial surgical consultation to resection was 31 (range 0-182) days. Age
      older than 65 years had a negative impact on wait time. Preoperative services,
      including computed tomography, cardiac consultation, echocardiography, multigated
      acquisition scan, magnetic resonance imaging, colonoscopy and cardiac
      catheterization also significantly increased wait times. Wait times were longer
      in rural hospitals. CONCLUSION: Preoperative services significantly increased
      wait times between initial surgical consultation and surgery.

PMID- 24666447
TI  - Laparoscopic sleeve gastrectomy: perioperative outcomes, weight loss and impact
      on type 2 diabetes mellitus over 2 years.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an increasingly performed
      operation for morbid obesity worldwide. To date there has been limited experience
      in Canada. We report our intermediate results, assessing whether LSG can be
      safely performed at a Canadian academic teaching hospital and whether it is
      effective as a bariatric procedure and as metabolic therapy for type 2 diabetes
      mellitus. METHODS: We performed a retrospective review of all patients who
      underwent LSG at our institution from Sept. 1, 2007, to June 30, 2011. RESULTS:
      We included 166 patients (mean age 44 yr, 82% female) in our study. The mean
      preoperative body mass index was 49.61. At baseline, 87 (52%) patients had type 2
      diabetes. For this subgroup, mean preoperative HbA1c and AC glucose were 7.6% and
      8.3 mmol/L, respectively. The mean duration of surgery was 93 minutes. Major
      complications included 1 staple line leak (0.6%), and 2 patients required
      reintervention for bleeding (1.2%). The mean hospital stay was 2.6 days. Two
      patients required readmission (1.2%). Seven minor complications occurred (4%).
      Postoperative excess weight loss was 49.3% at 6 months, 54.2% at 12 months and
      64.4% at 24 months. In the type 2 diabetes subgroup, resolution occurred in 78%
      and improvement in 7% of patients at 12 months. CONCLUSION: Laparoscopic sleeve
      gastrectomy can be safely performed at Canadian teaching hospitals. It is
      effective both as a bariatric procedure and as a therapeutic intervention for
      type 2 diabetes mellitus.

PMID- 24666448
TI  - Endoscopic management of gastric band erosions: a 7-year series of 14 patients.
AB  - BACKGROUND: Intragastric band migration is an unusual but major complication of
      gastric banding. We review our experience with endoscopic removal of eroded
      gastric bands. METHODS: We retrospectively evaluated the cases of 110 morbidly
      obese patients who underwent adjustable gastric banding between 2005 and 2012 to
      identify those who experienced band erosion. To remove the migrated band, we used
      an endoscopic approach with a Gastric Band Cutter. RESULTS: Band or tube erosion
      occurred in 14 patients (12.7%). The median time interval from the initial
      gastric band placement to the diagnosis of band erosion was 32 (range 18-52)
      months. Upper abdominal pain, port site infection, loss of restriction and weight
      regain were the most common symptoms. We used the Gastric Band Cutter to remove
      the band endoscopically. It was able to cut the band successfully in all but 1
      patient, in whom twisting of the cutting wire required conversion from endoscopy
      to laparotomy. In 2 patients, the band, after being cut, was locked in the
      gastric wall and required laparotomic removal. In 1 patient, we performed surgery
      for intragastric penetration of the connecting tube broken close to the band.
      CONCLUSION: The Gastric Band Cutter was successful in dividing the band in all
      but 1 patient, although we could not always complete the procedure
      endoscopically. Endoscopic removal seems to be effective and safe for band
      erosion.

PMID- 24666449
TI  - Distal revascularization and interval ligation (DRIL) procedure requires a long
      bypass for optimal inflow.
AB  - BACKGROUND: Distal revascularization and interval ligation (DRIL) is commonly
      used to treat ischemic steal syndrome caused by arteriovenous hemodialysis access
      and has been associated with good outcomes. However, the literature lacks
      technical details of a successful intervention. We tested the hypothesis that a
      brachial-level arteriovenous fistula (AVF) generates a zone of low arterial blood
      pressure in the brachial artery near the AVF origin. METHODS: We identified
      patients with ischemic steal syndrome caused by an AVF originating from the
      brachial artery level who were eligible for the DRIL procedure. All patients were
      studied with invasive pressure monitoring in the brachial artery at the time of
      digital subtraction angiography. We measured systolic, diastolic and mean
      arterial blood pressure at 5 cm intervals from a point in the arterial
      circulation 5 cm distal to the origin of the AVF and continuing proximally into
      the subclavian artery. RESULTS: Our series involved 10 patients with a mean age
      of 66.5 (range 53-81) years. Four patients were women and 8 had diabetes. All
      patients had grade 3 ischemic steal syndrome with ischemic rest pain and/or
      ischemic tissue loss. Mean systolic, diastolic and arterial pressures increased
      from the level of the AVF until central pressures were reached. Systolic blood
      pressure was significantly lower than central blood pressure until a level 20-25
      cm proximal to the AVF. CONCLUSION: The benefits of the DRIL procedure in
      alleviating ischemic steal syndrome associated with hemodialysis access are best
      achieved with a DRIL bypass for which inflow originates at least 20-25 cm
      proximal to the origin of the AVF.

PMID- 24666450
TI  - The role of the laparoendoscopic single site totally extraperitoneal approach to
      inguinal hernia repairs: a review and meta-analysis of the literature.
AB  - BACKGROUND: Laparoendoscopic single site (LESS) surgery may have perceived
      benefits of reduced visible scarring compared to conventional laparoscopic (LAP)
      totally extraperitoneal (TEP) hernia repairs. We reviewed the literature to
      compare LESS TEP inguinal hernia repairs with LAP TEP repairs. METHODS: We
      searched electronic databases for research published between January 2008 and
      January 2012. RESULTS: A total of 13 studies reported on 325 patients. The
      duration of surgery was 40-98 minutes for unilateral hernia and 41-121 minutes
      for bilateral repairs. Three studies involving 287 patients compared LESS TEP (n
      = 128) with LAP TEP (n = 159). There were no significant differences in operative
      duration for unilateral hernias (p = 0.63) or bilateral repairs (p = 0.29), and
      there were no significant differences in hospital stay (p > 0.99), intraoperative
      complications (p = 0.82) or early recurrence rates (p = 0.82). There was a trend
      toward earlier return to activity in the LESS TEP group (p = 0.07). CONCLUSION:
      Laparoendoscopic single site surgery TEP hernia repair is a relatively new
      technique and appears to be safe and effective. Advantages, such as less visible
      scarring, mean patients may opt for LESS TEP over LAP TEP. Further studies with
      clear definitions of outcome measures and robust follow-up to assess patient
      satisfaction, return to normal daily activities and recurrence are needed to
      strengthen the evidence.

PMID- 24666452
TI  - The effect of bariatric surgery on gastroesophageal reflux disease.
AB  - Obesity is an epidemic that is known to play a role in the development of
      gastroesophageal reflux disease (GERD). Studies have shown that increasing body
      mass index plays a role in the incompetence of the gastroesophageal junction and
      that weight loss and lifestyle modifications reduce the symptoms of GERD. As a
      method of producing effective and sustainable weight loss, bariatric surgery
      plays a major role in the treatment of obesity. We reviewed the literature on the
      effects of different types of bariatric surgery on the symptomatic relief of GERD
      and its complications. Roux-en- Y gastric bypass was considered an effective
      method to alleviate symptoms of GERD, whereas laparoscopic sleeve gastrectomy
      appeared to increase the incidence of the disease. Adjustable gastric banding was
      seen to initially improve the symptoms of GERD; however, a subset of patients
      experienced a new onset of GERD symptoms during long-term follow-up. The
      literature suggests that different surgeries have different impacts on the
      symptomatology of GERD and that careful assessment may be needed before
      performing bariatric surgery in patients with GERD. 

PMID- 24666451
TI  - Transanal endoscopic microsurgery: a review.
AB  - Rectal adenomas and cancers occur frequently. Small adenomas can be removed
      colonoscopically, whereas larger polyps are removed via conventional transanal
      excision. Owing to technical difficulties, adenomas of the mid- and upper rectum
      require radical resection. Transanal endoscopic microsurgery (TEM) was first
      designed as an alternative treatment for these lesions. However, since its
      development TEM has been also used for a variety of rectal lesions, including
      carcinoids, rectal prolapse and diverticula, early stage carcinomas and
      palliative resection of rectal cancers. The objective of this review is to
      describe the current status of TEM in the treatment of rectal lesions. Since the
      1980s, TEM has advanced substantially. With low recurrence rates, it is the
      method of choice for resection of endoscopically unresectable adenomas. Some
      studies have shown benefits to its use in treating early T1 rectal cancers
      compared with radical surgery in select patients. However, for more advanced
      rectal cancers TEM should be considered palliative or experimental. This
      technique has also been shown to be safe for the treatment of other uncommon
      rectal tumours, such as carcinoids. Transanal endoscopic microsurgery may allow
      for new strategies in the treatment of rectal pathology where technical
      limitations of transanal techniques have limited endoluminal surgical
      innovations. 

PMID- 24666453
TI  - Dislocation after the first and multiple revision total hip arthroplasty:
      comparison between acetabulum-only, femur-only and both component revision hip
      arthroplasty.
AB  - BACKGROUND: Dislocation may complicate revision total hip arthroplasty (THA). We
      examined the correlation between the components revised during hip arthroplasty
      (femur only, acetabulum only and both components) to the rates of dislocation in
      the first and multiple revision THA. METHODS: We obtained data from consecutive
      revision THAs performed between January 1982 and December 2005. Patients were
      grouped into femur-only revision, acetabulum-only revision and revision THA for
      both components. RESULTS: A total of 749 revision THAs performed during the study
      period met our inclusion criteria: 369 first-time revisions and 380 repeated
      revisions. Dislocation rates in patients undergoing first-time revisions (5.69%)
      were significantly lower than in those undergoing repeated revisions (10.47%; p =
      0.022). Within the group of first-time revisions, dislocation rates for
      acetabulum-only revisions (10.28%) were significantly higher than those for both
      components (4.61%) and femur-only (0%) reconstructions (p = 0.025). CONCLUSION:
      Although patients undergoing first-time revisions had lower rates of dislocations
      than those undergoing repeated revisions, acetabulum-only reconstructions
      performed at first-time revision arthroplasty entailed an increased risk for
      instability.

PMID- 24666454
TI  - A simple strategy to reduce stereotype threat for orthopedic residents.
AB  - BACKGROUND: Stereotype threat, defined as the predicament felt by people in
      either positive or negative learning experiences where they could conform to
      negative stereotypes associated with their own group membership, can interfere
      with learning. The purpose of this study was to determine if a simple orientation
      session could reduce stereotype threat for orthopedic residents. METHODS: The
      intervention group received an orientation on 2 occasions focusing on their
      possible responses to perceived poor performance in teaching rounds and the
      operating room (OR). Participants completed a survey with 7 questions typical for
      stereotype threat evaluating responses to their experiences. The questions had 7
      response options with a maximum total score of 49, where higher scores indicated
      greater degree of experiences typical of stereotype threat. RESULTS: Of the 84
      eligible residents, 49 participated: 22 in the nonintervention and 27 in the
      intervention group. The overall scores were 29 and 29.4, and 26.2 and 25.8 in the
      nonintervention and intervention groups for their survey responses to perceived
      poor performance in teaching rounds (p = 0.85) and the OR (p = 0.84),
      respectively. Overall, responses typical of stereotype threat were greater for
      perceived poor performance at teaching rounds than in the OR (p = 0.001).
      CONCLUSION: Residents experience low self-esteem following perceived poor
      performance, particularly at rounds. A simple orientation designed to reduce
      stereotype threat was unsuccessful in reducing this threat overall. Future
      research will need to consider longer-term intervention as possible strategies to
      reduce perceived poor performance at teaching rounds and in the OR.

PMID- 24666455
TI  - Hepatic parenchymal preserving technique in the management of diffuse bilateral
      neuroendocrine tumour liver metastases: a feasible approach.
AB  - BACKGROUND: Aggressive surgical resection of neuroendocrine tumour liver
      metastases (NET-LM) is associated with symptomatic relief. Debulking up to 90% of
      tumour burden, even with positive margins, may be beneficial. However, patients
      with diffuse hepatic metastases may not qualify for resection owing to associated
      insufficient remnant liver parenchyma. The purpose of this study is to describe
      an early experience with a hepatic parenchymal preserving (HPP) approach.
      METHODS: We retrospectively reviewed our institutional neuroendocrine tumours
      database to identify patients with NET-LM, including symptomatic patients with
      extensive bilobar involvement, who underwent virtual volumetric assessment (VVA)
      combined with HPP resection between October 2008 and July 2011. RESULTS: Our
      study involved 9 patients. The median number of liver metastases resected was 10
      (range 4-50). Symptomatic improvement was observed in all patients. Immediate
      postoperative normalization of 5-HIAA 24-hour urine levels occurred in 89% of
      patients. Symptomatic and biochemical response remained stable or improved in 75%
      of patients at 12 months of follow-up. Four patients had postoperative
      complications. There was no 90-day mortality. CONCLUSION: The described HPP
      approach is feasible and safe. Most patients experienced symptomatic and
      biochemical improvement. This reproducible approach could expand surgical
      resection options for patients with NET-LM and diffuse bilobar involvement.

PMID- 24666456
TI  - Spine surgeons' requirements for imaging at the time of referral: a survey of
      Canadian spine surgeons.
AB  - BACKGROUND: Routine imaging of patients with spine-related complaints referred
      for surgical assessment may represent an inefficient use of technological
      resources. Our objective was to explore Canadian spine surgeons' requirements
      with respect to imaging studies accompanying spine-related referrals. METHODS: We
      administered an 8-item survey to all 100 actively practising surgeon members of
      the Canadian Spine Society that inquired about demographic variables and imaging
      requirements for patients referred with spine-related complaints. RESULTS: Fifty
      five spine surgeons completed our survey, for a response rate of 55%. Most
      respondents (43; 78%) required imaging studies to accompany all spine-related
      referrals. The type of imaging required was highly variable, with respondents
      endorsing 7 different combinations. Half (47%) required magnetic resonance
      imaging and 38% required plain radiographs either alone or in combination with
      other forms of imaging. Half of the respondents refused to see 20% or more of all
      patients referred for spine-related complaints. CONCLUSION: Most Canadian spine
      surgeons require imaging studies to accompany spine-related referrals; however,
      the type and combination of studies is highly variable, and many patients who are
      referred are never seen (for a consultation). Standardization and optimization of
      imaging practices for patients with spine-related complaints referred for
      surgical assessment may be an important area for cost savings.

PMID- 24666457
TI  - "iBIM"--internet-based interactive modules: an easy and interesting learning tool
      for general surgery residents.
AB  - BACKGROUND: The increased use of information technology supports a resident-
      centred educational approach that promotes autonomy, flexibility and time
      management and helps residents to assess their competence, promoting self
      awareness. We established a web-based e-learning tool to introduce general
      surgery residents to bariatric surgery and evaluate them to determine the most
      appropriate implementation strategy for Internet-based interactive modules (iBIM)
      in surgical teaching. METHODS: Usernames and passwords were assigned to general
      surgery residents at the University of Alberta. They were directed to the
      Obesity101 website and prompted to complete a multiple-choice precourse test.
      Afterwards, they were able to access the interactive modules. Residents could
      review the course material as often as they wanted before completing a multiple
      choice postcourse test and exit survey. We used paired t tests to assess the
      difference between pre- and postcourse scores. RESULTS: Out of 34 residents who
      agreed to participate in the project, 12 completed the project (35.3%). For these
      12 residents, the precourse mean score was 50 +/- 17.3 and the postcourse mean
      score was 67 +/- 14 (p = 0.020). CONCLUSION: Most residents who participated in
      this study recommended using the iBIMs as a study tool for bariatric surgery.
      Course evaluation scores suggest this novel approach was successful in
      transferring knowledge to surgical trainees. Further development of this tool and
      assessment of implementation strategies will determine how iBIM in bariatric
      surgery may be integrated into the curriculum.

PMID- 24666458
TI  - Current management of penetrating torso trauma: nontherapeutic is not good enough
      anymore.
AB  - A highly organized approach to the evaluation and treatment of penetrating torso
      injuries based on regional anatomy provides rapid diagnostic and therapeutic
      consistency. It also minimizes delays in diagnosis, missed injuries and
      nontherapeutic laparotomies. This review discusses an optimal sequence of
      structured rapid assessments that allow the clinician to rapidly proceed to gold
      standard therapies with a minimal risk of associated morbidity. 

PMID- 24666460
TI  - Massive panniculectomy: a novel method of treatment of postlaparotomy wound
      dehiscence in morbid obesity.

PMID- 24666459
TI  - Prognostic factors for morbidity and mortality in elderly patients undergoing
      acute gastrointestinal surgery: a systematic review.
AB  - BACKGROUND: Elderly patients undergoing acute gastrointestinal (GI) surgery
      experience increased morbidity and mortality compared with younger and elective
      patients. Prognostic factors can be used to counsel patients of these risks and,
      if modifiable, to minimize them. We reviewed the literature on prognostic factors
      for adverse outcomes in elderly patients undergoing acute GI surgery. METHODS: We
      searched PubMed and Embase using a strategy developed in collaboration with an
      expert librarian. Studies examining independent associations between prognostic
      factors and morbidity or mortality in patients aged 65 and older undergoing acute
      GI surgery were selected. We extracted data using a standardized form and
      assessed study quality using the QUIPS tool. RESULTS: Nine cohort studies
      representing 2958 patients satisfied our selection criteria. All studies focused
      on postoperative mortality. Thirty-four prognostic factors were examined, with
      significant variability across studies. There was limited or conflicting evidence
      for most prognostic factors. Meta-analysis was only possible for the American
      Society of Anesthesiologists (ASA) score, which was found to be associated with
      mortality in 4 studies (pooled odds ratio 2.77, 95% confidence interval 0.92
      8.41). CONCLUSION: While acute GI surgery in elderly patients is becoming
      increasingly common, the literature on prognostic factors for morbidity and
      mortality in this patient population lags behind. Further research is needed to
      help guide patient care and potentially improve outcomes.

PMID- 24666461
TI  - Ancillary tests to improve the accuracy of laparoscopy in the diagnosis of
      tuberculous peritonitis.

PMID- 24666462
TI  - Implementation of an acute care emergency surgical service: a cost analysis from
      the surgeon's perspective.
AB  - BACKGROUND: Acute care surgical services provide comprehensive emergency general
      surgical care while potentially using health care resources more efficiently. We
      assessed the volume and distribution of emergency general surgery (EGS)
      procedures before and after the implementation of the Acute Care and Emergency
      Surgery Service (ACCESS) at a Canadian tertiary care hospital and its effect on
      surgeon billings. METHODS: This single-centre retrospective case-control study
      compared adult patients who underwent EGS procedures between July and December
      2009 (pre-ACCESS), to those who had surgery between July and December 2010 (post
      ACCESS). Case distribution was compared between day (7 am to 3 pm), evening (3 pm
      to 11 pm) and night (11 pm to 7 am). Frequencies were compared using the chi(2)
      test. RESULTS: Pre-ACCESS, 366 EGS procedures were performed: 24% during the day,
      55% in the evening and 21% at night. Post-ACCESS, 463 operations were performed:
      55% during the day, 36% in the evening and 9% at night. Reductions in night-time
      and evening EGS were 57% and 36% respectively (p < 0.001). Total surgeon billings
      for operations pre- and post-ACCESS were $281 066 and $287 075, respectively:
      remuneration was $6008 higher post-ACCESS for an additional 97 cases (p = 0.003).
      Using cost-modelling analysis, post-ACCESS surgeon billing for appendectomies,
      segmental colectomies, laparotomies and cholecystectomies all declined by $67
      190, $125 215, $66 362, and $84 913, respectively (p < 0.001). CONCLUSION: Acute
      care surgical services have dramatically shifted EGS from nighttime to daytime.
      Cost-modelling analysis demonstrates that these services have cost-savings
      potential for the health care system without reducing overall surgeon billing.

PMID- 24666463
TI  - Association between tumor necrosis factor-alpha gene polymorphisms and prostate
      cancer risk: a meta-analysis.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory
      cytokine that may play a role in controlling the progression of prostate cancer.
      Two common polymorphisms in the TNF-alpha gene, -308G/A and -238C/T, have been
      suggested to alter the risk for prostate cancer, but the results have been
      inconclusive so far. In order to obtain a better understanding of the effects of
      these two polymorphisms on prostate cancer risk, all available studies were
      considered in a meta-analysis. METHODS: We conducted a comprehensive literature
      search in the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature
      database (CBM), and the China National Knowledge Infrastructure (CNKI). The
      associations were evaluated by calculating the pooled odds ratio (OR) with 95%
      confidence interval (95% CI). RESULTS: In this meta-analysis, we included 14
      studies with 5,757 patients and 6,137 control subjects for the TNF-alpha-308G/A
      polymorphism and 1,967 patients and 2,004 control subjects for the TNF-alpha
      238C/T polymorphism. A significantly increased prostate cancer risk was found to
      be associated with the TNF-alpha-308C/T polymorphism in studies with healthy
      volunteers (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093-2.145; P = 0.013; AG vs.
      GG: OR = 1.477, 95% CI = 1.047-2.085; P = 0.026). No significant association was
      found between the TNF-alpha-238G/A polymorphism and prostate cancer risk in the
      overall or subgroup analyses. There was no risk of publication bias in this meta
      analysis. CONCLUSIONS: Our results suggest that while the TNF-alpha-238G/A
      polymorphism may not be associated with prostate cancer the TNF-alpha-308C/T
      polymorphism may significantly contribute to prostate cancer susceptibility in
      healthy volunteers. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1629288120116301.

PMID- 24666464
TI  - Effect of music on pain, anxiety, and patient satisfaction in patients who
      present to the emergency department in Turkey.
AB  - AIM: The objective of this study is to evaluate the effect of music therapy on
      pain, anxiety, and patient satisfaction in patients who present to the emergency
      department in Turkey. METHODS: This controlled and experimental study was
      conducted in the emergency department of a hospital in Turkey between July and
      October 2012. The study sample consisted of 200 patients in total, 100 forming
      the intervention group and 100 being the control group, who fell under color code
      green in the triage system and came with complaints of pain due to
      nausea/vomiting and diarrhea, abdominal pain, headaches, and joint pain. A
      questionnaire, the State Anxiety Scale, and the Visual Analog Scale to measure
      the patients' level of pain were used in the study. The questionnaires of the
      intervention group were administered after playing the music. RESULTS: When the
      intervention and control groups were compared, it was observed that there was a
      significant decrease in the VASP and STAI-S scores in favor of the intervention
      group. It was observed that 21.0% of the patients in the intervention group were
      very pleased to hear music in the emergency department, 58% of them were
      moderately or at least a little pleased, and 21.0% were not pleased at all.
      CONCLUSION: The results showed that music therapy had a positive effect in terms
      of reducing the severity of pain and the level of anxiety in patients, that only
      a very small portion of the patients were not pleased to listen to music in the
      emergency department.

PMID- 24666465
TI  - Intravenous infusion of electrolyte solution changes pharmacokinetics of drugs:
      pharmacokinetics of ampicillin.
AB  - The pharmacokinetics of ampicillin in dogs was determined after intravenous
      (i.v.) bolus and constant rate infusion. Ampicillin was administered to six
      beagle dogs as an i.v. bolus at 20 mg/kg and as a constant rate i.v. infusion
      (CRI) at 20 mg/kg during 8 h (0.042 mL/min/kg) in Ringer's lactate (Hartmann's)
      solution. The concentrations were determined by an LC/MS/MS method. After i.v.
      bolus, ampicillin total body clearance, apparent volume of distribution at steady
      state, mean residence time (MRT), and half-life were 4.53 +/- 0.70 mL/min/kg,
      0.275 +/- 0.044 L/kg, 61 +/- 13 min, and 111 (85-169) min, respectively. The
      corresponding parameters calculated after CRI were 13.5 +/- 1.06 mL/min/kg, 0.993
      +/- 0.415 L/kg, 73 +/- 27 min, and 49 (31-69) min. Ampicillin concentration
      decreased by 30% in the Ringer's lactate infusion solution mostly during the
      first hour after preparation of the solution. Constant rate infusion of Ringer's
      lactate solution during 8 h caused significant changes in ampicillin
      pharmacokinetics. The results suggested that special attention should be given to
      drug pharmacokinetics when co-administered intravenously with electrolyte
      solutions. 

PMID- 24666466
TI  - Reduced residual gene expression of nuclear factor of activated T cells-regulated
      genes correlates with the risk of cytomegalovirus infection after liver
      transplantation.
AB  - BACKGROUND: Pharmacokinetic monitoring of calcineurin inhibitors (CNIs) is
      unsatisfactory because, at comparable blood concentrations, side effects vary
      considerably. We recently confirmed the applicability of a pharmacodynamic (PD)
      assay that measures the suppression of CNI target genes, specifically the
      suppression of nuclear factor of activated T cells (NFAT)-regulated genes in
      liver transplant (LT) recipients. The aim of this prospective study was to prove
      the clinical reliability of this assay. Therefore, we quantified the residual
      gene expression (RGE) of NFAT-regulated genes and evaluated the association
      between the RGE of NFAT-regulated genes and the incidence of cytomegalovirus
      (CMV) infection. PATIENTS AND METHODS: In 20 LT recipients, 10 patients on
      cyclosporine (CsA) and 10 patients on tacrolimus (Tac) therapy, who presented
      with CMV infection, the RGEs of interleukin-2, interferon-gamma (IFNgamma), and
      granulocyte-monocyte colony-stimulating factor were measured and compared with
      the RGEs of these cytokines in 40 healthy dose-matched LT controls. RESULTS: CsA
      treated CMV patients demonstrated a lower RGE of all NFAT-regulated genes
      compared with controls (30 +/- 17 vs. 44 +/- 20, P = 0.067). For IFNgamma, the
      level of significance was reached (26 +/- 17 vs. 43 +/- 17, P = 0.0125). Daily
      CsA dosage, CsA baseline (C0 ) and 2 h (C2 ) concentrations were comparable (CsA
      dosage 169 mg/day vs. 165 mg/day; CsA C0 94 MUg/L vs. 85 MUg/L; CsA C2 389 MUg/L
      vs. 381 MUg/L). In addition, Tac-treated CMV patients demonstrated a lower RGE of
      all NFAT-regulated genes compared with controls (68 +/- 25 vs. 84 +/- 22, P =
      0.0769). Analogous to CsA-treated CMV patients, the level of significance was
      reached for IFNgamma (61 +/- 24 vs. 88 +/- 29, P = 0.0154). Daily Tac dosage and
      Tac 1.5 h concentrations (C1.5 ) were comparable in both groups (Tac dosage 4
      mg/day vs. 4 mg/day; Tac C1.5 8 MUg/L vs. 10 MUg/L), whereas Tac C0
      concentrations were significantly higher in controls (Tac C0 4 MUg/L vs. 6 MUg/L,
      P = 0.0276). CONCLUSION: Measuring the RGE of NFAT-regulated genes is appropriate
      to assess the risk of infections in LT recipients. Measuring the RGE of IFNgamma
      is particularly suitable to assess the risk of CMV infection. PD monitoring of
      CNIs in LT recipients is an approach to individualize immunosuppression, which
      may help to reduce infectious complications.

PMID- 24666467
TI  - The ethical tightrope: politics of intimacy and consensual method in sexuality
      research.
AB  - This paper seeks to analyze the construction of ethics in sexuality research in
      which qualitative methods are employed in the field of social sciences. Analyses
      are based on a bibliographic review of current discussions on research methods of
      queer theory and on the authors' own experiences of past research on sexuality.
      The article offers a theoretical perspective on the ways ethnography and in-depth
      interviews become methods that can rely on a consensual method and create a
      politics of intimacy between the researchers and research participants. The
      politics of intimacy may contribute to the production of a politically engaged
      knowledge while escaping from the moral matrix that usually governs the
      relationship between researchers and research participants. It is argued here
      that the researcher's sexed and gendered body matters for fieldwork; that the
      consensual method among participants may be employed in sexuality research as a
      fruitful tool; and that the relationships created among researchers and
      participants can pose a challenge to predetermined ethical guidelines in
      research. As a result, discussions problematize the existence of a politics of
      intimacy in sexuality research that is characterized by ethical relations among
      research participants. 

PMID- 24666468
TI  - Essential infantile esotropia: postoperative motor outcomes and inferential
      analysis of strabismus surgery.
AB  - BACKGROUND: The aim of this retrospective study is a long-term evaluation of
      postoperative motor outcomes and the inferential analysis of strabismus surgery
      in infant eyes with essential infantile esotropia. METHODS: 576 patients were
      compatible with the criteria: confirmed EIE diagnosis, angle >= 30 pD, absence of
      associated ocular anomalies, onset by 6 months of age, absence of hyperopia > 3
      Diopters, operation before age 4. Preoperative deviation classes (30-40 pD, 41-59
      pD, >= 60 pD) were established, different types of surgery were performed. Follow
      up was conducted for 5 years after surgery. Longitudinal data were analyzed using
      general linear mixed models stratified according to the class of pre-operative
      deviation. A random intercept and a random slope with time (in months) was
      assumed with an unstructured within subject correlation structure for repeated
      measurements. RESULTS: In patients with preoperative angle <= 40 pD, a
      significant interaction effect for intervention by time (F5,155.9 = 3.56, p =
      0.004) and a significant intervention effect (F5,226.1 = 6.41, p < 0.001) on
      residual deviation were observed; only the intervention 5 showed a residual
      deviation inside the limits of a partial success. In Class 41-59, a significant
      interaction effect for intervention by time (F4,166.7 = 5.16, p = 0.001),
      intervention (F4,178.1 = 2.48, p = 0.046) and time (F1,174.6 = 9.99, p = 0.002)
      on residual deviation were observed; intervention 7 had the highest degree of
      stability showing an outcome within the range of a partial success. In Class >=
      60 pD no significant effect for intervention (F4,213.9 = 0.74, p = 0.567), time
      (F1,169.5 = 0.33, p = 0.569) or intervention by time (F4,160.9 = 1.08, p = 0.368)
      on residual deviation was observed; intervention 3,6 and 7 resulted in a residual
      deviation within the range of a partial success. CONCLUSIONS: We suggest, where
      possible, a two-horizontal muscles approach in small angle EIE, while a multiple
      muscles surgery in large angle EIE.

PMID- 24666469
TI  - Genomic evaluation of both purebred and crossbred performances.
AB  - BACKGROUND: For a two-breed crossbreeding system, Wei and van der Werf presented
      a model for genetic evaluation using information from both purebred and crossbred
      animals. The model provides breeding values for both purebred and crossbred
      performances. Genomic evaluation incorporates marker genotypes into a genetic
      evaluation system. Among popular methods are the so-called single-step methods,
      in which marker genotypes are incorporated into a traditional animal model by
      using a combined relationship matrix that extends the marker-based relationship
      matrix to non-genotyped animals. However, a single-step method for genomic
      evaluation of both purebred and crossbred performances has not been developed
      yet. RESULTS: An extension of the Wei and van der Werf model that incorporates
      genomic information is presented. The extension consists of four steps: (1) the
      Wei van der Werf model is reformulated using two partial relationship matrices
      for the two breeds; (2) marker-based partial relationship matrices are
      constructed; (3) marker-based partial relationship matrices are adjusted to be
      compatible to pedigree-based partial relationship matrices and (4) combined
      partial relationship matrices are constructed using information from both
      pedigree and marker genotypes. The extension of the Wei van der Werf model can be
      implemented using software that allows inverse covariance matrices in sparse
      format as input. CONCLUSIONS: A method for genomic evaluation of both purebred
      and crossbred performances was developed for a two-breed crossbreeding system.
      The method allows information from crossbred animals to be incorporated in a
      coherent manner for such crossbreeding systems.

PMID- 24666470
TI  - Molecular characterization of an Australian serotype 1 Streptococcus pneumoniae
      outbreak.
AB  - Serotype 1 Streptococcus pneumoniae is a cause of invasive pneumococcal disease
      (IPD) worldwide and has been associated with IPD outbreaks, while carriage is
      rarely detected in healthy adults or children. This study details an Australian
      multi-state and territory outbreak of serotype 1 S. pneumoniae IPD between 2010
      and 2012. Molecular characterization demonstrated the outbreak was largely due to
      the clonal expansion of sequence type 306, MLVA type 261 S. pneumoniae serotype
      1.

PMID- 24666472
TI  - The new American guidelines on hypertension: a favorable opinion.

PMID- 24666471
TI  - A study of clinical and information management processes in the surgical pre
      assessment clinic.
AB  - BACKGROUND: Establishing day-case surgery as the preferred hospital admission
      route for all eligible patients requires adequate preoperative assessment of
      patients in order to quickly distinguish those who will require minimum
      assessment and are suitable for day-case admission from those who will require
      more extensive management and will need to be admitted as inpatients. METHODS: As
      part of a study to elucidate clinical and information management processes within
      the patient surgical pathway in NHS Scotland, we conducted a total of 10 in-depth
      semi-structured interviews during 4 visits to the Dumfries & Galloway Royal
      Infirmary surgical pre-assessment clinic. We modelled clinical processes using
      process-mapping techniques and analysed interview data using qualitative methods.
      We used Normalisation Process Theory as a conceptual framework to interpret the
      factors which were identified as facilitating or hindering information
      elucidation tasks and communication within the multi-disciplinary team. RESULTS:
      The pre-assessment clinic of Dumfries & Galloway Royal Infirmary was opened in
      2008 in response to clinical and workflow issues which had been identified with
      former patient management practices in the surgical pathway. The preoperative
      clinic now operates under well established processes and protocols. The use of a
      computerised system for managing preoperative documentation substantially
      transformed clinical practices and facilitates communication and information
      sharing among the multi-disciplinary team. CONCLUSION: Successful deployment and
      normalisation of innovative clinical and information management processes was
      possible because both local and national strategic priorities were synergistic
      and the system was developed collaboratively by the POA staff and the health
      board IT team, resulting in a highly contextualised operationalisation of
      clinical and information management processes. Further concerted efforts from a
      range of stakeholders are required to fully integrate preoperative assessment
      within the health-board surgical care pathway. A substantial - yet unfulfilled -
      potential benefit in embedding information technology in routine use within the
      preoperative clinic would be to improve the reporting of surgical outcomes.

PMID- 24666473
TI  - Hepatitis C virus: a silent killer relevant to dentistry.
AB  - Around 25 years ago, hepatitis C virus (HCV) was identified, and following
      intense research and tremendous advancements, the infection is now potentially
      curable and even complete viral eradication is possible. It is also evident that
      HCV can be involved in some oral disorders, but more research is clearly
      warranted on oral health of HCV-infected patients. Given the global estimates on
      HCV epidemic and its likely huge economic impact, primary prevention and
      secondary prevention are worldwide priorities. However, investments are still
      insufficient to achieve these goals. 

PMID- 24666474
TI  - Radiologic features of breast cancer after mantle radiation therapy for Hodgkin
      disease: a study of 230 cases.
AB  - PURPOSE: To retrospectively review diagnostic mammography in women diagnosed with
      breast cancer who previously had mantle field radiation therapy for Hodgkin
      disease in England and Wales over a period of 30 years. MATERIALS AND METHODS:
      From a national cohort study of 5002 women treated with supradiaphragmatic
      radiation therapy when they were younger than 36 years (mean, 22.1 years) during
      1956-2003, 392 patients developed breast cancer. With ethics committee approval
      and informed consent, mammograms were obtained that showed 230 tumors in 222
      (56.6%) patients from 95 hospitals, and the size and appearance of each carcinoma
      was recorded by two breast radiologists. Comparison was made with a historical
      report of more than 1000 general-population breast cancers by using Pearson
      chi(2) test. RESULTS: Thirty-eight tumors were occult on mammograms. Mean tumor
      maximum diameter was 12.3 mm (n = 81) on oblique view. The quadrant distribution
      of the tumors was significantly different (P < .001) from the historic controls,
      and chest radiation therapy patients had a greater proportion of tumors in the
      upper outer (66.9% [107 of 160] vs 48.7% [385 of 784]) and, to a lesser extent,
      lower inner (10.6% [17 of 160] vs 7.8% [61 of 784]) quadrants. The dominant
      radiologic feature was of an irregular mass (56.8% [109 of 192]) followed by
      microcalcifications (25.0% [48 of 192]). CONCLUSION: This study suggests that in
      patients who previously underwent mantle radiation therapy for Hodgkin disease,
      breast cancers are more commonly seen within the upper outer quadrants than are
      cancers in the general population. Poorly defined masses were the most common
      appearance.

PMID- 24666475
TI  - Diode laser photoablation to correct distal nasolacrimal duct atresia in an adult
      horse.
AB  - CASE DESCRIPTION: An 8-year-old Hanoverian mare was presented for chronic
      mucopurulent discharge in the left eye, which was responsive to topical
      antibiotic therapy. CLINICAL FINDINGS: The nasolacrimal orifice was absent in the
      left nasal meatum, and anterograde irrigation of left nasolacrimal duct was not
      possible. Dacryocystorhinography was performed and revealed about 4-6 cm of
      distal nasolacrimal duct atresia. SURGICAL TREATMENT AND OUTCOME: A novel
      technique was attempted with the horse under standing sedation using an urinary
      catheter and a 980 nm diode laser with a 600 MUm diameter flexible bare quartz
      fiber. A nasolacrimal orifice was successfully created by ablating the nasal
      mucosa directly over the tip of the urinary catheter, and patency was maintained
      with a soft catheter sutured in place for 4 weeks. At 3 months re-evaluation, the
      left nasolacrimal duct was patent and functional. CONCLUSION: This case report
      describes a successful novel surgical technique used to correct congenital distal
      nasolacrimal duct atresia in an adult horse under standing sedation. Advantages
      over conventional surgical techniques are shorter operating time and limited
      hemorrhage.

PMID- 24666476
TI  - [Transmission of antiretroviral drug resistant strains in patients diagnosed with
      human immunodeficiency virus infection in Gran Canaria in the period 2009-2012].

PMID- 24666478
TI  - Probing the chemical structure in diamond-based materials using combined low-loss
      and core-loss electron energy-loss spectroscopy.
AB  - We report the analysis of the changes in local carbon structure and chemistry
      caused by the self-implantation of carbon into diamond via electron energy-loss
      spectroscopy (EELS) plasmon energy shifts and core-edge fine structure
      fingerprinting. These two very different EELS energy and intensity ranges of the
      spectrum can be acquired under identical experimental conditions and nearly
      simultaneously using specially designed deflectors and energy offset devices
      known as "DualEELS." In this way, it is possible to take full advantage of the
      unique and complementary information that is present in the low- and core-loss
      regions of the EELS spectrum. We find that self-implanted carbon under the
      implantation conditions used for the material investigated in this paper creates
      an amorphous region with significant sp 2 content that varies across the
      interface. 

PMID- 24666477
TI  - Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular
      administration of a single dose of 8 mg/kg: dose proportionality, influence of
      the age of the animals and urinary elimination.
AB  - The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of
      dose and animal age following intravenous and intramuscular administration of a
      16% solution (Forcyl((r)) ). The absolute bioavailability of marbofloxacin as
      well as the dose proportionality was evaluated in 27-week-old fattening pigs.
      Blood PK and urinary excretion of marbofloxacin were evaluated after a single
      intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12
      week-old weaned piglets was used for the evaluation of age-related kinetics. The
      plasma and urine concentration of marbofloxacin was determined using a HPLC
      method. Pharmacokinetic parameters were calculated using noncompartmental
      methods. After intravenous administration in 27-week-old fattening pigs, the
      total body clearance was 0.065 L/h.kg. After intramuscular administration to the
      same animals, the mean observed Cmax was 6.30 MUg/mL, and the AUCINF was 115
      MUg.h/mL. The absolute bioavailability was 91.5%, and dose proportionality was
      shown within the dose range of 4-16 mg/kg. The renal clearance was about half of
      the value of the total clearance. The total systemic clearance values
      significantly decreased as a function of age, being 0.092 L/h.kg and 0.079 L/h.kg
      in pigs aged 12 and 16 weeks, respectively. 

PMID- 24666479
TI  - Minor surgical procedures and musculoskeletal injections by primary care
      physicians - an Israeli experience.
AB  - ABSTARCT BACKGROUND: Since minor surgical and musculoskeletal problems are
      commonly seen in primary care, primary care physicians are expected to possess
      the skills required to perform minor surgical procedures (MSP) and
      musculoskeletal injections (MSI). OBJECTIVE: To evaluate the performance of MSP
      and MSI by primary care physicians in the Southern District (Negev) of Clalit
      Health Services (CHS) health maintenance organization (HMO) in Israel. METHODS: A
      structured self-report questionnaire was sent to all 277 primary care physicians,
      other than pediatricians, working in the Southern District (Negev) of CHS HMO.
      RESULTS: One hundred fifty one of the 277 questionnaires (54%) were completed and
      returned. Sixty five percent of the primary care physicians perform any MSP and
      46% perform any MSI. The main barriers reported for performing MSP and MSI were
      lack of time (74% and 66%, respectively) and training (41% and 60%,
      respectively). Forty percent of the physicians cited remuneration as a potential
      motivating factor. A logistic regression model showed that male physicians and
      physicians who work full or part-time in rural areas, are more likely to perform
      MSP (Odds ratio 2.12 and 2.24, respectively). Male physicians, especially board
      certified family physicians, are more likely to perform MSI (Odds ratio 2.86 and
      7.0 respectively). CONCLUSION: MSP and MSI are practiced by only some primary
      care physicians. HMOs and individuals responsible for designing training
      curricula in family medicine and primary care can encourage primary care
      physicians to perform MSP and MSI by providing courses, specific compensation,
      and dedicated time. This can strengthen the bond between primary care physicians
      and patients, reduce waiting time for patients, and save money for HMO's.

PMID- 24666480
TI  - [Decitabine in myelodysplastic syndromes: the current status and future].

PMID- 24666481
TI  - [Study on the induction and differentiation of megakaryocyte progenitor cell
      derived from umbilical cord blood].
AB  - OBJECTIVE: To build a protocol of separation and induction of megakaryocytes
      derived from cord blood mononuclear cells. METHODS: Red blood cells were
      precipitated by hydroxyethyl starch (HES). Mononuclear cells were obtained by
      density gradient centrifugation with Ficoll. The inducing efficiencies of
      megakaryocytes by using of different cytokine cocktails and culture media were
      analyzed. RESULTS: The best choice for erythrocyte sedimentation and high
      efficiency of nucleated cells retrieving were obtained by using of 1.5% HES. The
      isolated cord blood mononuclear cells were cultured with domestic serum-free
      medium supplemented with 116t (IL-11, IL-6, TPO), st36(SCF, TPO, IL-3, IL-6),
      pt36 (PDGF,TPO,IL-3,IL-6) or pst36 for 7 days. St36 group (50 ng/ml SCF, 50 ng/ml
      TPO, 20 ng/ml IL-3 and 50 ng/ml IL-6) yielded the most CD41/CD61 positive
      [(6.79+/-1.97)*104]. The cell viability [(82.85 +/- 0.64)%] of st36 group by
      using of imported serum-free medium was better than [(60.90+/-6.93)%] that in
      domestic medium on day 7 after induction, and CD41/CD61 positive cells count
      [(18.60+/-1.97)*104] were more than domestic serum-free medium group. Therefore,
      we chose imported serum-free medium containing st36 to induce cord blood
      mononuclear cells. After a prolonged culture, the total cell numbers increased
      accompanied with an elevated percentage of CD41/CD61 positive cells, which
      reached (54.27 +/- 6.31)% on day 14. Wright-Giemsa staining showed that different
      phase cells, such as megakaryoblast, promegakaryocyte and granular megakaryocyte,
      occurred after 10 days'culture. Clone forming unit-megakarocytes (CFU-MK) assay
      showed that the colonies count increased with the prolonged incubation. CFU-MK
      colonies were [1 236.0+/-32.9] on day 14, which was higher than that in medium
      without induction (P<0.01). Platelets from megakaryocytes showed agglutination
      function after 10 days'culture. CONCLUSION: 1.5% HES was the best solution to
      precipitate erythrocytes. The combination of an imported serum-free medium with
      IL-3, IL-6, SCF and TPO showed better induction efficiency than domestic medium
      or other cytokine cocktails. Meanwhile, induced megakaryocytes produced
      functional platelets.

PMID- 24666482
TI  - [The functional study of antithrombin L99 mutation].
AB  - OBJECTIVE: To study the molecular mechanisms of inherited antithrombin (AT)
      deficiency caused by AT L99 mutation. METHODS: Wild type (WT), L99V, L99A, L99I
      and L99S AT were purified from drosophila expression system. The binding capacity
      of AT and the low molecular weight heparin sodium was analyzed by the heparin
      binding assay. Surface plasmon resonance (SPR) was used to detect the binding
      ability of AT to thrombin (FIIa) or AT to coagulation factor Xa (FXa). The
      activity of AT(AT?A)was detected by chromogenic assay. RESULTS: The purified WT
      and mutant AT were at the same size. No additional band was observed by coomassie
      blue staining and western blot assay. Compared to the WT AT, the binding
      abilities of the low molecular weight heparin sodium to the AT L99V, L99A, L99I
      and L99S were (44.8+/-3.6)%, (118.9+/-14.0)%, (15.2+/-8.8)%, and(23.0+/-8.2)%,
      respectively. The binding abilities of FIIa to AT L99V, L99A, L99I and L99S were
      13%, 57%, 3%, and 29%, while the binding of FXa to AT L99V, L99A, L99I and L99S
      were 7%, 51%, 1%, and 25%. The AT?A of WT, L99V, L99A, L99I and L99S AT were
      146.5%, 21.4%, 120.9%, 10.8%, and 39.0%, respectively. CONCLUSION: The binding
      abilities of AT to heparin, FIIa and FXa were damaged by the L99 mutation, which
      resulted in decreased AT?A and inherited AT deficiency.

PMID- 24666483
TI  - [Effects of arsenic trioxide on the methylation of TMS1 gene in K562 cells].
AB  - OBJECTIVE: To detect the methylation status of TMS1 gene and its demethylation by
      arsenic trioxide (As2O3) in K562 cells. METHODS: K562 cells were treated with
      different concentrations of As2O3 for 48 hours. Methylation-specific PCR (MSP)
      was used to determine the methylation status of TMS1. RT-PCR and Western blot
      were used to detect the levels of TMS1 mRNA and protein. TMS1 associated
      apoptosis proteins Bcl-2/Bax were also analyzed by Western blot. Apoptosis were
      evaluated by flow cytometry using Annexin V/propium iodide (PI) double staining.
      RESULTS: TMS1 gene was completely methylated in K562 cells and the levels of TMS1
      mRNA and protein were low (0.01+/-0.01, 0.09+/-0.02), which could be reversed
      (mRNA: 0.72+/-0.04; protein: 1.30+/-0.06; P<0.01) by 2 MUmol/L As2O3 via overt
      demethylation of TMS1 gene. Apoptosis in experiment group (12.24+/-1.06) was
      significantly higher than that in control group (2.05+/-0.16, P<0.05). In
      experiment group, the down-expression of antiapoptotic protein Bcl-2 and up
      expression of pro-apoptotic protein Bax led to an obvious decline ratio of Bcl
      2/Bax (0.56+/-0.12), as compared to the control group (1.94+/-0.14, P<0.01).
      CONCLUSION: As2O3 could up-regulate TMS1 gene expression by reversing its
      hypermethylation and induced apoptosis by down-regulation of Bcl-2/Bax ratio in
      K562 cells.

PMID- 24666484
TI  - [Culture and regulation of osteoblasts in multiple myeloma patients].
AB  - OBJECTIVE: To investigate the biological characteristics of osteoblasts cultured
      in vitro from bone marrow (BM) of multiple myeloma (MM) patients and to explore
      their generation and osteogenic potential. Effects of some factors such as
      bortezomib and MM patient serum on the osteoblasts were observed. METHODS: Twenty
      MM patients and 10 healthy donors as controls were enrolled in this study.
      Osteoblasts from MM patients'BM were cultured in vitro. The generation and
      osteogenic potential of osteoblasts from MM patients and normal subjects were
      compared. The changes of their osteogenic potential and biological
      characteristics were observed. The antigens (CD34,CD138,CD45) on osteoblasts were
      catalyzed by flow cytometry. The levels of IL-7 were measured by ELISA. The BMP2
      mRNAs were measured by RT-PCR. RESULTS: Osteoblasts from MM patients'BM could be
      cultured in vitro. The quantity of osteoblasts from MM patients (6.3+/-1.5) was
      less than normal subjects (8.2+/-2.6) (P<0.05). The osteoblasts cultured with MM
      patient serum (7.4+/-1.1) were less than those without patient serum (8.2+/-2.6)
      (P<0.05). Bortezomib increased those from MM patients after 6 days culture (8.9+/
      2.1 vs 6.3+/-1.5) (P<0.05). Von Kossa staining showed that there were more
      calcium depositions in MM osteoblasts with bortezomib (8.8+/-1.9) than those
      without bortezomib (6.1+/-1.6) (P<0.05), but less than those from normal controls
      (15.8+/-2.2) (P<0.05). CD138, CD45, CD34 were not detected on the cultured cells.
      The level of IL-7 in MM patients'serum (2.07+/-0.71) was higher than that in
      normal controls (1.62+/-0.15) (P<0.05). The expression of BMP2 mRNA was seen in
      the normal osteoblasts and MM patients'osteoblasts cultured with bortezomib, but
      not be seen in those without bortezomib. CONCLUSION: Osteoblasts could be
      cultured in vitro from MM patients' BM. The proliferation and osteogenic
      potential of osteoblasts from MM patients were decreased. Bortezomib was a
      positive regulatory of osteoblasts and MM patient serum was a negative one. They
      both could affect the proliferation and osteogenic potential of osteoblasts.

PMID- 24666485
TI  - [Detection of BRAF V600E mutation in hairy cell leukemia by high- resolution
      melting analysis].
AB  - OBJECTIVE: To explore the feasibility and diagnostic implication of BRAF V600E
      mutation identified by high-resolution melting (HRM) assay in patients with hairy
      cell leukemia (HCL). METHODS: The V600E mutation of BRAF exon 15 in four HCL
      patients were detected by HRM assay and patients' clinical data were
      retrospectively analyzed. RESULTS: All four HCL patients were positive for the
      BRAF V600E mutation, which were identical to the results of DNA sequencing.
      CONCLUSION: The HRM assay for BRAF V600E mutation provides a useful tool to aid
      the laboratory diagnosis of HCL with easy operability, accuracy, and low cost.

PMID- 24666486
TI  - [A clinical and laboratory study of chronic myeloid leukemia with atypical BCR
      ABL fusion gene subtypes].
AB  - OBJECTIVE: To explore the clinical and laboratory features of chronic myeloid
      leukemia (CML) with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.
      METHODS: We retrospectively analyzed a cohort of CML patients with Ph chromosome
      positive confirmed by cytogenetic and FISH but classical e13a3(b2a2),
      e14a2(b3a2)and e1a2 fusion transcripts negative identified by conventional real
      time quantification RT-PCR (RQ-PCR). Further RQ-PCR was done with the forward
      primer and reverse primer designed to detect rare atypical BCR-ABL fusion genes
      including e14a3 and e19a2 transcripts. Direct sequencing analysis was performed
      on the PCR products and mutations in the BCR-ABL kinase domain were detected. The
      clinical data of patients were retrospectively analyzed. RESULTS: Six CML
      patients were found to carry t(9;22) abnormality and BCR-ABL rearrangement
      confirmed by FISH but classical BCR-ABL fusion genes negative detected by RQ-PCR.
      Further RQ-PCR and sequencing analysis confirmed the fusion of BCR exon 14 and
      ABL exon 3 in five CML patients (case 1-5) and the fusion of BCR exon 19 and ABL
      exon 2 in one CML patient (case 6). E255K and I293T IM-resistant mutations were
      detected in case 1 and 2, respectively. Among five cases with e14a3 transcripts,
      four were CML-CP, one CML-AP. Four patients were male and one was female. The
      median age was 48 years. The patient (case 6) with e19a2 transcripts was 40-year
      old female with a diagnosis of CML-CP and PLT count was more than 1 000*109/L.
      Imatinib (IM) therapy was administer in case 1, 2, 3, 4 and hematopoietic stem
      cell transplantation (HSCT) was undergone in case 5 after hydroxyurea (Hu) or
      interferon failure. Case 1 who had E255K IM resistant mutation, responded poorly
      to IM but obtained a complete cytogenetic remission (CCyR) after a substitution
      of dasatinib for IM. Case 2 and 3 achieved CCyR 6 months later after IM treatment
      and had been maintained well with IM despite I293T mutation in case 2. Case 4
      attained CCyR 3 months later after IM treatment but relapsed and died soon. Case
      5 was still in CCyR after HSCT. Case 6 with e19a2 transcripts got complete
      hematologic response after Hu treatment and CCyR was achieved soon after IM
      therapy. CONCLUSION: Incidence of CML with atypical transcripts is extremely low.
      They could benefit from tyrosine kinase inhibitors or HSCT. Rare and atypical BCR
      ABL fusion gene subtypes could be missed by conventional RQ-PCR.

PMID- 24666487
TI  - [IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA
      matched sibling donor allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To explore the impact of interleukin-18 (IL-18) single nucleotide
      polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling
      donor hematopoietic stem cell transplantation (allo-HSCT). METHODS: Single-
      nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific
      primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors.
      Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and
      infections, transplant related mortality (TRM), and disease free survival (DFS)
      were analyzed. RESULTS: In comparison with -137 G/C+C/C donor genotype, patients
      with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11
      23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD
      (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery
      [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic
      GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that
      (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype
      also had higher incidence (33.3%) of extensive chronic GVHD than those with
      C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM,
      and DFS between different genotypes. CONCLUSION: IL-18 -137 G homozygous genotype
      in donor facilitated neutrophil reconstitution, but increased the risk of
      extensive chronic GVHD in patients with allo-HSCT.

PMID- 24666488
TI  - [Fludarabine-based increased-intensity conditioning regimen for allogeneic
      hematopoietic stem cell transplantation in acquired severe aplastic anemia].
AB  - OBJECTIVE: To observe the effects of increased-intensity conditioning regimen
      with FBCA (Fludarabine, Busulfan, Cyclophosphamide, and Antithymocyte globulin)
      for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acquired
      severe aplastic anemia (SAA). METHODS: From January 2000 to June 2011, twenty-two
      patients (male 12, female 10) with SAA underwent allo-HSCT with FBCA conditioning
      regimen which consisted of fludarabine (30 mg.m-2.d-1*5 d), busulfan (3 mg/kg*2
      d), cyclophosphamide (60 mg.kg-1.d-1*2 d) and ATG (2.5 mg.kg-1.d-1*5 d). GVHD
      prophylaxis was performed by cyclosporine and short-term course methotrexate.
      Nine patients received mobilized peripheral blood stem cells transplantation and
      13 patients underwent mobilized peripheral blood combined with bone marrow stem
      cells. Fourteen cases were human leukocyte antigen (HLA)-matched related donors,
      while the other 8 cases were HLA-haploidentical transplantation. Engraftment was
      documented by short tandem repeats with polymerase chain reaction (STR-PCR) on
      approximately day + 30, + 90, + 180, + 1 year and + 2 year, respectively. Long
      term survival and transplantation-related complications were analyzed. RESULTS:
      All patients obtained prompt and sustained hematopoietic reconstitution. Median
      time for neutrophil and PLT engraftment was 15 (range: 11-22) days and 16 (range:
      12-27) days, respectively. All patients were full donor chimerism identified by
      STR-PCR. 2 of the total 22 cases (9.1%) had grade I-III acute GVHD and 3 (15.8%)
      was chronic GVHD. Three patients (13.6%) died of transplantation related
      mortality and the other 19 cases were disease-free survival with a median time of
      24 (range: 0.5-140.5) months. The causes of death were cytomegalovirus pneumonia
      (n=1), acute GVHD (n=1) and severe pulmonary infection (n=1). CONCLUSION:
      Increased-intensity of FBCA conditioning regimen could favor donor stem cell
      sustained engraftment for allo-HSCT in SAA.

PMID- 24666489
TI  - [Bortezomib-based chemotherapy for patients with multiple myeloma: a single
      center experience].
AB  - OBJECTIVE: To evaluate the efficacy and safety of bortezomib-based chemotherapy
      for 80 patients with multiple myeloma (MM). METHODS: A total of 80 cases with a
      median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib
      based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib,
      doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo
      hematopoietic stem cell transplantation (HSCT). RESULTS: The overall response
      (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median
      follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and
      72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%,
      respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT,
      while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In
      univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial
      response (VGPR), and HSCT were prognostic factors for OS. Gender and
      extramedullary plasmacytomas were important prognostic factors for PFS.
      Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon
      group A, and HSCT were prognostic factors for better OS; while male and patients
      without extramedullary plasmacytomas were prognostic factors for longer PFS.
      CONCLUSION: MM patients could benefit from bortezomib-based chemotherapy with
      satisfactory efficacy and safety. HSCT could improve the OS for young MM
      patients.

PMID- 24666490
TI  - [Comparison of 18F-FDG PET/CT and large-scale DWI for evaluation of non-Hodgkin
      lymphoma bone marrow infiltration].
AB  - OBJECTIVE: To compare the diagnostic value of 18F-fluorodeoxyglucose-positron
      emission tomography/computed tomography (18F-FDG PET/CT) and large-scale
      diffusion weighted imaging (DWI) for evaluation of non-Hodgkin lymphoma (NHL)
      bone marrow (BM) infiltration. METHODS: A total of 79 patients with
      pathologically diagnosed NHL underwent 18F-FDG PET/CT, large scale DWI and BM
      pathological examination. BM examination as the "gold standard", the performance
      (the sensitivity, specificity, accuracy, positive and negative predictive value)
      of 18F-FDG PET/CT and large scale DWI for evaluation of BM infiltration was
      compared and the risk of BM infiltration of different subtypes and sources of NHL
      was analyzed. RESULTS: 25 of 79 cases were diagnosed as BM infiltration by
      pathological examination with 57 BM sites. Abnormal high BM metabolisms were
      identified in 22 cases with 56 BM sites by 18F-FDG PET/CT and 25 cases with 58 BM
      sites by large-scale DWI. The sensitivity, specificity, accuracy, positive and
      negative predictive value of 18F-FDG PET/CT were 80.0%, 96.3%, 91.1%, 90.9%,
      91.2%, respectively. And they were 84.0%, 92.6%, 89.9%, 84.0%, and 92.6% by large
      scale DWI, respectively. A receiver operating characteristic (ROC) analysis
      demonstrated that there was no statistical difference in 18F-FDG PET/CT and large
      scale DWI (P>0.05). The area under ROC curve for 18F-FDG PET/CT and large-scale
      DWI were 0.911 and 0.883 respectively. The incidences of BM infiltration in
      aggressive NHL patients by 18F-FDG PET/CT (21/69, 30.4%) and large-scale DWI
      (23/69, 33.3%) were higher than those (PET/CT: 10.0%; large-scale DWI: 20.0%;
      P>0.05) in indolent NHL patients. CONCLUSION: 18F-FDG PET/CT and large-scale DWI
      had important clinical value in diagnosing BM infiltration of NHL. A combination
      of 18F-FDG PET/CT, large-scale DWI and pathological examination could improve the
      positive rate of BM infiltration in NHL.

PMID- 24666491
TI  - [Lower dose of rituximab in the treatment of elderly autoimmune hemolytic
      anemia].
AB  - OBJECTIVE: To explore the safety and efficacy of lower dose of rituximab in the
      treatment of elderly autoimmune hemolytic anemia (AIHA). METHODS: From May 2008
      to February 2013, a total of 37 patients with newly diagnosed elderly AIHA
      patients were enrolled in the study, including 25 cases treated with prednisone 1
      mg . kg-1 . d-1 for 4 weeks and 12 cases ineligible for glucocorticoid receiving
      rituximab (100 mg/week for 4 times). RESULTS: Of the 25 patients with
      conventional glucocorticoid, 5 cases (20.0%) were complete remission (CR), 15
      cases with partial remission (PR) and 5 cases without response. The overall
      response rate was 80.0%. Of the 12 cases with rituximab, 8 cases (66.7%) were CR,
      3 cases with PR and 1 without response. The overall response rate was 91.7%. A
      significantly higher CR rate was seen in lower dose of rituximab, as compared to
      that in conventional glucocorticoid (P=0.038). CONCLUSION: A lower dose of
      rituximab, with satisfactory safety and efficacy, was better than the
      conventional glucocorticoid in the treatment of elderly AIHA patients.

PMID- 24666492
TI  - [A case report of pure red cell aplasia secondary to Richter syndrome].

PMID- 24666493
TI  - [The prevalence of Acinetobacter baumannii in hematology ward of single center
      from 2010 to 2012].

PMID- 24666494
TI  - [Study on the correlation between FcgammaR IIIA-158V/F single nucleotide
      polymorphisms and adult primary immune thrombocytopenia].

PMID- 24666495
TI  - [Resveratrol can reduce the expression of WT1 by methylation in K562 cells].

PMID- 24666496
TI  - [Effects of arsenic trioxide on Id4 methylation status in bone marrow mononuclear
      cells and its clinical efficacy for myelodysplastic syndrome].

PMID- 24666497
TI  - [Outcome of autologous hematopoietic stem cell transplantation in combination
      with imatinib for 16 cases of Philadelphia chromosome positive acute
      lymphoblastic leukemia].

PMID- 24666498
TI  - [Allogeneic hematopoietic stem cell transplantation for aggressive-phase chronic
      myeloid leukemia -- outcomes of unrelated umbilical cord blood and sibling
      donor].

PMID- 24666499
TI  - [Observation of low-dose HA/HAA regimen as induction chemotherapy on elderly
      patients with acute myeloid leukemia].

PMID- 24666500
TI  - [The family-based research and genetic diagnosis of beta-thal major in Dai
      ethnic].

PMID- 24666501
TI  - [Alternative donor transplantation in adult hematologic malignancies].

PMID- 24666502
TI  - [A case report of prostate sarcoma with bone marrow metastasis].

PMID- 24666503
TI  - [Anticomplement treatment of PNH in the era of Eculizumab: problems and outlook].

PMID- 24666504
TI  - [Hotspot report of 55th American Society of Hematology Annual Meeting:
      hematopoietic stem cell transplantation].

PMID- 24666505
TI  - [Hotspot report of 55th American Society of Hematology annual meeting: acute
      leukemia].

PMID- 24666506
TI  - [Hotspot report of 55th American Society of Hematology annual meeting: primary
      immune thrombocytopenia].

PMID- 24666507
TI  - Medication prescribing for asthma and COPD: a register-based cross-sectional
      study in Swedish primary care.
AB  - BACKGROUND: There is a gap between prescribed asthma medication and diagnosed
      asthma in children and adolescents. However, few studies have explored this issue
      among adults, where asthma medication is also used for the treatment of chronic
      obstructive pulmonary disease (COPD). The aim of this study was to examine the
      relationship between prescribing of medications indicated for asthma and COPD and
      the recorded diagnosis for these conditions. METHOD: In a register-based study,
      individuals prescribed a medication indicated for asthma and COPD during 2004
      2005 (Group A; n = 14 101) and patients with diagnoses of asthma or COPD recorded
      during 2000-2005 (Group B; n = 12 328) were identified from primary health care
      centers in Skaraborg, Sweden. From a 5% random sample of the medication users (n
      = 670), the written medical records were accessed. PRIMARY OUTCOMES: prevalence
      of medication and diagnoses, reasons for prescription. SECONDARY OUTCOMES: type
      and number of prescribed drugs and performance of peak expiratory flow or
      spirometry. RESULTS: Medications indicated for asthma and COPD was prescribed to
      5.6% of the population in primary care (n = 14 101). Among them, an asthma
      diagnosis was recorded for 5876 individuals (42%), 1116 (8%) were diagnosed with
      COPD and 545 (4%) had both diagnoses. The remaining 6564 individuals (46%) were
      lacking a recorded diagnosis. The gap between diagnosis and medication was
      present in all age-groups. Medication was used as a diagnostic tool among 30% of
      the undiagnosed patients and prescribed off-label for 54%. Missed recording of
      ICD-codes for existing asthma or COPD accounted for 16%. CONCLUSION: There was a
      large discrepancy between prescribing of medication and the prevalence of
      diagnosed asthma and COPD. Consequently, the prevalence of prescriptions of
      medications indicated for asthma and COPD should not be used to estimate the
      prevalence of these conditions. Medication was used both as a diagnostic tool and
      in an off-label manner. Therefore, the prescribing of medications for asthma and
      COPD does not adhere to national clinical guidelines. More efforts should be made
      to improve the prescribing of medication indicated for asthma and COPD so that
      they align with current guidelines.

PMID- 24666508
TI  - Folic acid-conjugated 4-amino-phenylboronate, a boron-containing compound
      designed for boron neutron capture therapy, is an unexpected agonist for human
      neutrophils and platelets.
AB  - Boron neutron capture therapy (BNCT) is an anticancer treatment based on the
      accumulation in the tumor cells of (10) B-containing molecules and subsequent
      irradiation with low-energy neutrons, which bring about the decay of (10) B to
      very toxic (7) Li(3+) and (4) He(2+) ions. The effectiveness of BNCT is limited
      by the low delivery and accumulation of the used (10) B-containing compounds.
      Here, we report the development of folic acid-conjugated 4-amino-phenylboronate
      as a novel possible compound for the selective delivery of (10) B in BNCT. An
      extensive analysis about its biocompatibility to mature blood cells and platelet
      progenitors revealed that the compound markedly supports platelet aggregation,
      neutrophil oxidative burst, and inhibition of megakaryocyte development, while it
      does not have any manifest effect on red blood cells. 

PMID- 24666509
TI  - Sugammadex and anaphylaxis in the operating theater.

PMID- 24666510
TI  - Anesthesia for bariatric surgery: 8-year retrospective study: are our patients
      now easier to manage?
AB  - OBJECTIVES: To review the perioperative management of patients who had undergone
      bariatric surgery in our institution during an 8-year period, with the aim of
      identifying variables that correlated with improved clinical outcomes and changes
      in perioperative practice. METHODS: This was a retrospective observational study
      of 437 patients who had undergone bariatric surgery from January 2005 to June
      2013. Of these patients, 163 had undergone open or laparoscopic biliopancreatic
      diversion (Group 1), and 274 had been managed according to a Tailored
      Laparoscopic Approach Program (TLAP) (Group 2). We analyzed major
      cardiocirculatory, pulmonary, and surgery-related complications, mortality rate,
      intensive care unit (ICU) admissions, post-anesthetic care unit (PACU) length of
      stay, and perioperative management standards, throughout the study period.
      RESULTS: Changes were observed in anesthetic patterns and perioperative care
      standards during the study period: 25% of patients had combined epidural
      anesthesia in 2005, compared with none at present; ICU admissions decreased from
      28.6% in 2005 to 3.1% at present; and time in PACU declined from a median of 23 h
      in 2005 to 5.12h at present. Duration of postoperative opioid therapy was also
      significantly reduced (from 48 h to 6h). Group 2 had a significantly lower
      mortality rate than Group 1 (0.37% versus 4.3%, respectively, P=0.004).
      CONCLUSIONS: In our institution, adoption of a TLAP for bariatric surgery has led
      to changes in perioperative care standards that have been followed by clear
      improvements according to morbidity, mortality and management indicators.

PMID- 24666511
TI  - Combined effects of nitrogen addition and litter manipulation on nutrient
      resorption of Leymus chinensis in a semi-arid grassland of northern China.
AB  - Plant growth in semi-arid ecosystems is usually severely limited by soil nutrient
      availability. Alleviation of these resource stresses by fertiliser application
      and aboveground litter input may affect plant internal nutrient cycling in such
      regions. We conducted a 4-year field experiment to investigate the effects of
      nitrogen (N) addition (10 g N.m(-2) .year(-1)) and plant litter manipulation on
      nutrient resorption of Leymus chinensis, the dominant native grass in a semi-arid
      grassland in northern China. Although N addition had no clear effects on N and
      phosphorus (P) resorption efficiencies in leaves and culms, N fertilisation
      generally decreased leaf N resorption proficiency by 54%, culm N resorption
      proficiency by 65%. Moreover, N fertilisation increased leaf P resorption
      proficiency by 13%, culm P resorption proficiency by 20%. Under ambient or
      enriched N conditions, litter addition reduced N and P resorption proficiencies
      in both leaves and culms. The response of P resorption proficiency to litter
      manipulation was more sensitive than N resorption proficiency: P resorption
      proficiency in leaves and culms decreased strongly with increasing litter amount
      under both ambient and enriched N conditions. In contrast, N resorption
      proficiency was not significantly affected by litter addition, except for leaf N
      resorption proficiency under ambient N conditions. Furthermore, although litter
      addition caused a general decrease of leaf and culm nutrient resorption
      efficiencies under both ambient and enriched N conditions, litter addition
      effects on nutrient resorption efficiency were much weaker than the effects of
      litter addition on nutrient resorption proficiency. Taken together, our results
      show that leaf and non-leaf organs of L. chinensis respond consistently to
      altered soil N availability. Our study confirms the strong effects of N addition
      on plant nutrient resorption processes and the potential role of aboveground
      litter, the most important natural fertiliser in terrestrial ecosystems, in
      influencing plant internal nutrient cycling.

PMID- 24666512
TI  - SPECT myocardial perfusion versus fractional flow reserve for evaluation of
      functional ischemia: a meta analysis.
AB  - PURPOSE: The present meta-analysis illustrates the accuracy of myocardial
      perfusion SPECT (MPS) to diagnose functional stenotic coronary artery disease
      (CAD) with fractional flow reserve (FFR) as standard reference. METHODS: All
      investigators screened and selected studies that compared MPS with FFR in
      symptomatic patients with suspected CAD. Patients and study characteristics were
      independently extracted by two investigators; differences were resolved by
      consensus. RESULTS: 13 articles, including 1,017 patients, 699 vessels were
      included in the study. No significant publication bias was detected (P=0.65). At
      the patient level, the summary sensitivity and specificity were 77% (95%
      confidence interval [CI], 70-83%) and 77% (95%CI, 67-84%) for MPS. Vessel-level
      pooled sensitivity was 66% (95%CI, 57-74%) and specificity was 81% (95%CI, 70
      89%). The overall diagnostic performance of MPS was moderate. [The area under the
      summary receiver operating characteristic (sROC) curve was 0.83]. No study
      influenced the pooled results larger than 0.03. CONCLUSIONS: The accuracy between
      FFR and MPS SPECT was moderate.

PMID- 24666513
TI  - Underestimation of invasive lesions in patients with ductal carcinoma in situ of
      the breast diagnosed by ultrasound-guided biopsy: a comparison between patients
      with and without HER2/neu overexpression.
AB  - PURPOSE: To determine the rate of underestimation of ductal carcinoma in situ
      (DCIS) diagnosed at imaging-guided biopsy and to analyze its association with
      HER2/neu oncogene, an important biomarker in assessing the tumour aggressiveness
      and guiding hormone therapy for breast cancer. METHODS: We retrospectively
      reviewed 162 patients with DCIS diagnosed by imaging-guided core needle biopsy
      between January 2008 and March 2013. All of these patients received surgical
      excision, and in 25, the diagnosis was upgraded to invasive breast cancer. In
      this study, we examined the ultrasound, mammographic features and
      histopathological results for each patient, and compared these parameters between
      those with and without HER2/neu overexpression. RESULTS: Of the 162 DCIS lesions,
      110 (67.9%) overexpressed HER2/neu. Nineteen patients with HER2/neu
      overexpressing DCIS (n=19/110, 17.3%) were upgraded after surgery to a diagnosis
      of invasive breast cancer. In this group, the upgrade rate was highest in
      patients with a dilated mammary duct pattern (42.1%, n=8/19, p=0.02) and the
      presence of abnormal axillary nodes (40.0%, n=12/30, p<0.01) at ultrasound and
      was significantly associated with comedo tumour type on pathology. CONCLUSIONS:
      Biopsy may underestimate the invasive component in DCIS patients. Sonographic
      findings of dilated mammary ducts and presence of abnormal axillary lymph nodes
      may help predicting the invasive components and possibly driving more targeted
      biopsy procedures.

PMID- 24666515
TI  - Acute painful neuropathy in a heroin body packer.

PMID- 24666514
TI  - Serum paraoxonase 1 (PON1) measurement: an update.
AB  - Paraoxonase 1 (PON1) is a widely studied enzyme based on its protective role
      against poisoning by organophosphate (OP) metabolites of specific OP insecticides
      and in vascular disease, as well as its use as biomarker of diseases involving
      oxidative stress, inflammation and liver diseases.This review provides an update
      about the current knowledge in the field of the analytical procedures that are
      used for PON1 measurements. It will be specially focused on: (a) characteristics
      of the different substrates used for measuring PON1, with emphasis in four
      aspects: toxicity, polymorphism influence, rate of hydrolysis and diagnostic
      performance. And (b) the technical aspects of PON1 assays, in which the reagents
      and reaction conditions, sources of variation, quality control systems, equipment
      and interferences with other esterases will be discussed.The information provided
      in this review can contribute to a more accurate and safe measurements of PON1 in
      laboratories and encourage researchers to explore the wide areas of PON1 in
      veterinary medicine that are still unknown. 

PMID- 24666518
TI  - Novel therapies targeting eosinophilic inflammation in asthma.

PMID- 24666516
TI  - Amelioration of adriamycin-induced cardiotoxicity by Salsola kali aqueous extract
      is mediated by lowering oxidative stress.
AB  - OBJECTIVES: To assess the cardioprotective effect of the Salsola kali aqueous
      extract against adriamycin (ADR)-induced cardiotoxicity in male Swiss albino
      mice. METHODS: The aqueous extract of S. kali was phytochemically screened by
      traditional methods for different classes and further evaluated for antioxidant
      activity in vitro. In vivo, cardioprotective evaluation of the extract was
      designed to have four groups of mice: (1) control group (distilled water, orally;
      normal saline, intraperitoneally (i.p.)); (2) ADR group (15 mg/kg, i.p.); (3)
      aqueous S. kali extract (200 mg/kg, orally); and (4) ADR + S. kali group. ADR (5
      mg/kg) was injected three times over 2 weeks while S. kali was orally
      administered daily for 3 weeks (1 week before and 2 weeks during ADR treatment).
      Cardioprotective properties were assessed using biochemical and histopathological
      approaches. RESULTS: ADR caused a significant increase in serum enzymes (lactate
      dehydrogenase, creatine phosphokinase, aspartate aminotransferase, and alanine
      aminotransferase). Myocardial levels of malondialdehyde, nitric oxide, and
      reduced glutathione, as well as the activities of superoxide dismutase and
      catalase increased while the activities of glutathione peroxidase and glutathione
      S-transferase declined. Histopathological examination of heart sections revealed
      that ADR caused myofibrils loss, necrosis and cytoplasmic vacuolization.
      DISCUSSION: Pretreatment with S. kali aqueous extract normalized serum and
      antioxidant enzymes minimized lipid peroxidation and cardiac damage. These
      results have suggested that the extract has antioxidant activity, indicating that
      the mechanism of cardioprotection during ADR treatment is mediated by lowering
      oxidative stress.

PMID- 24666519
TI  - Is there a place for B cells as regulators of immune tolerance in allergic
      diseases?

PMID- 24666520
TI  - Cleaning agents and disinfectants: moving from recognition to action and
      prevention.

PMID- 24666522
TI  - Chronic alcohol alters rewarded behaviors and striatal plasticity.
AB  - Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated
      by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the
      effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors.
      Ex vivo electrophysiological recordings revealed loss in efficacy of DLS
      synaptically induced activation and absent long-term depression after CIE. CIE
      increased two-bottle choice drinking and impaired Pavlovian-to-instrumental
      transfer but not discriminated approach. These data suggest prolonged CIE
      impaired DLS plasticity, to produce associated changes in drinking and cue
      controlled reward-seeking. Given recent evidence that less-prolonged CIE can
      promote certain dorsal striatal-mediated behaviors, CIE may drive chronicity
      dependent adaptations in corticostriatal systems regulating behavior. 

PMID- 24666524
TI  - Combined treatment for Coats' disease: retinal laser photocoagulation combined
      with intravitreal bevacizumab injection was effective in two cases.
AB  - BACKGROUND: The exact pathogenetic mechanisms of Coats' disease remain unknown.
      In this report, we show two cases of Coats' disease that achieved a favorable
      prognosis with the combined treatment of intravitreal bevacizumab (IVB) injection
      prior to photocoagulation, although both initially resisted photocoagulation
      therapy. CASE PRESENTATIONS: Case 1 was a 15-year-old boy with initial visual
      acuity of 0.4 OD. At the temporal retina, aneurysms and abnormal telangiectatic
      vessels were observed. Hard exudates and an exudative retinal detachment extended
      to the fovea. He was diagnosed as having Coats' disease at stage 3A and we
      performed laser photocoagulation as an initial approach to treat peripheral
      aneurysms and telangiectatic vessels. After the treatment, the exudative retinal
      detachment was eased and visual acuity improved to 1.0; however, recurrence
      occurred after 5 months. The exudative change was resistant against laser
      photocoagulation therapy and we therefore added IVB as an adjuvant before
      photocoagulation. Fourteen days after IVB injection phased laser photocoagulation
      was given to cover the abnormal capillaries, aneurysms and the leakage area
      spotted in FA. A good prognosis was obtained with decreased exudation and
      improved visual acuity.Case 2 was an 11-year-old boy with decreased visual acuity
      of 0.15 OS at the initial visit. Hard exudates, retinal edema and serous retinal
      detachment were seen at the macula and peripheral retina. Fluorescein angiography
      revealed telangiectatic capillaries at the temporal retina. Our diagnosis was
      Coats' disease at stage 3A. Extensive photocoagulation was performed as an
      initial treatment to the lesion. However, the exudative change was severe and
      resistant against the photocoagulation treatment. Therefore, we added IVB as an
      adjuvant before photocoagulation. Exudative change in the retina seemed to be
      eased 7 days after IVB injection, therefore, phased laser phototherapy was added
      to cover the abnormal capillaries. After the combination therapy, exudative
      change was remarkably ameliorated and better visual acuity was achieved.
      CONCLUSION: Bevacizumab is considered an effective adjuvant for Coats' disease
      with exudative change resistant to retinal photocoagulation therapy.

PMID- 24666525
TI  - Gender disparity in LDL-induced cardiovascular damage and the protective role of
      estrogens against electronegative LDL.
AB  - BACKGROUND: Increased levels of the most electronegative type of LDL, L5, have
      been observed in the plasma of patients with metabolic syndrome (MetS) and ST
      segment elevation myocardial infarction and can induce endothelial dysfunction.
      Because men have a higher predisposition to developing coronary artery disease
      than do premenopausal women, we hypothesized that LDL electronegativity is
      increased in men and promotes endothelial damage. METHODS: L5 levels were
      compared between middle-aged men and age-matched, premenopausal women with or
      without MetS. We further studied the effects of gender-influenced LDL
      electronegativity on aortic cellular senescence and DNA damage in leptin receptor
      deficient (db/db) mice by using senescence-associated-beta-galactosidase and
      gammaH2AX staining, respectively. We also studied the protective effects of
      17beta-estradiol and genistein against electronegative LDL-induced senescence in
      cultured bovine aortic endothelial cells (BAECs). RESULTS: L5 levels were higher
      in MetS patients than in healthy subjects (P < 0.001), particularly in men (P =
      0.001). LDL isolated from male db/db mice was more electronegative than that from
      male or female wild-type mice. In addition, LDL from male db/db mice contained
      abundantly more apolipoprotein CIII and induced more BAEC senescence than did
      female db/db or wild-type LDL. In the aortas of db/db mice but not wild-type
      mice, we observed cellular senescence and DNA damage, and the effect was more
      significant in male than in female db/db mice. Pretreatment with 17beta-estradiol
      or genistein inhibited BAEC senescence induced by male or female db/db LDL and
      downregulated the expression of lectin-like oxidized LDL receptor-1 and tumor
      necrosis factor-alpha protein. CONCLUSION: The gender dichotomy of LDL-induced
      cardiovascular damage may underlie the increased propensity to coronary artery
      disease in men.

PMID- 24666523
TI  - Genetic polymorphisms modify bladder cancer recurrence and survival in a USA
      population-based prognostic study.
AB  - OBJECTIVE: To identify genetic variants that modify bladder cancer prognosis
      focusing on genes involved in major biological carcinogenesis processes
      (apoptosis, proliferation, DNA repair, hormone regulation, immune surveillance,
      and cellular metabolism), as nearly half of patients with bladder cancer
      experience recurrences reliable predictors of this recurrent phenotype are needed
      to guide surveillance and treatment. PATIENTS AND METHODS: We analysed variant
      genotypes hypothesised to modify these processes in 563 patients with urothelial
      cell carcinoma enrolled in a population-based study of incident bladder cancer
      conducted in New Hampshire, USA. After diagnosis, patients were followed over
      time to ascertain recurrence and survival status, making this one of the first
      population-based studies with detailed prognosis data. Cox proportional hazards
      regression was used to assess the relationship between single nucleotide
      polymorphisms (SNPs) and prognosis endpoints. RESULTS: Patients with aldehyde
      dehydrogenase 2 (ALDH2) variants had a shorter time to first recurrence (adjusted
      non-invasive hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.29-2.78).
      There was longer survival among patients with non-invasive tumours associated
      with DNA repair X-ray repair cross-complementing protein 4 (XRCC4) heterozygous
      genotype compared with wild-type (adjusted HR 0.53, 95% CI 0.38-0.74). Time to
      recurrence was shorter for patients who had a variant allele in vascular cellular
      adhesion molecule 1 (VCAM1) and were treated with immunotherapy (P interaction <
      0.001). CONCLUSIONS: Our analysis suggests candidate prognostic SNPs that could
      guide personalised bladder cancer surveillance and treatment.

PMID- 24666526
TI  - Impact of multimorbidity: acute morbidity, area of residency and use of health
      services across the life span in a region of south Europe.
AB  - BACKGROUND: Concurrent diseases, multiple pathologies and multimorbidity patterns
      are topics of increased interest as the world's population ages. To explore the
      impact of multimorbidity on affected patients and the consequences for health
      services, we designed a study to describe multimorbidity by sex and life-stage in
      a large population sample and to assess the association with acute morbidity,
      area of residency and use of health services. METHODS: A cross-sectional study
      was conducted in Catalonia (Spain). Participants were 1,749,710 patients aged 19+
      years (251 primary care teams). PRIMARY OUTCOME: Multimorbidity (>=2 chronic
      diseases). Secondary outcome: Number of new events of each acute disease. Other
      variables: number of acute diseases per patient, sex, age group (19-24, 25-44, 45
      64, 65-79, and 80+ years), urban/rural residence, and number of visits during
      2010. RESULTS: Multimorbidity was present in 46.8% (95% CI, 46.7%-46.8%) of the
      sample, and increased as age increased, being higher in women and in rural areas.
      The most prevalent pair of chronic diseases was hypertension and lipid disorders
      in patients older than 45 years. Infections (mainly upper respiratory infection)
      were the most common acute diagnoses. In women, the highest significant RR of
      multimorbidity vs. non-multimorbidity was found for teeth/gum disease (aged 19
      24) and acute upper respiratory infection. In men, this RR was only positive and
      significant for teeth/gum disease (aged 65-79). The adjusted analysis showed a
      strongly positive association with multimorbidity for the oldest women (80+
      years) with acute diseases and women aged 65-79 with 3 or more acute diseases,
      compared to patients with no acute diseases (OR ranged from 1.16 to 1.99, p <
      0.001). Living in a rural area was significantly associated with lower
      probability of having multimorbidity. The odds of multimorbidity increased
      sharply as the number of visits increased, reaching the highest probability in
      those aged 65-79 years. CONCLUSIONS: Multimorbidity is related to greater use of
      health care services and higher incidence of acute diseases, increasing the
      burden on primary care services. The differences related to sex and life-stage
      observed for multimorbidity and acute diseases suggest that further research on
      multimorbidity should be stratified according to these factors.

PMID- 24666527
TI  - Amygdala-frontal couplings characterizing SSRI and placebo response in social
      anxiety disorder.
AB  - In patients with social anxiety disorder (SAD) it has been reported that
      selective serotonin reuptake inhibitors (SSRIs) and placebo induce anxiolytic
      effects by attenuating neural activity in overlapping amygdala subregions, i.e.
      left basolateral and right ventrolateral amygdala. However, it is not known
      whether these treatments inhibit amygdala subregions via similar or distinct
      brain pathways. As anxiolytic treatments may alter amygdala-frontal couplings we
      investigated differences and similarities in amygdala-frontal functional co
      activation patterns between responders and nonresponders to SSRIs and placebo in
      patients with SAD. Positron emission tomography (PET) with oxygen-15-labeled
      water was used to measure anxiety-related regional cerebral blood flow in 72
      patients with SAD before and after 6-8 wk of treatment under double-blind
      conditions. Functional couplings were evaluated with a seed region approach using
      voxel values from the left basolateral and right ventrolateral amygdala.
      Responders and nonresponders to SSRIs and placebo showed different treatment
      induced co-activations between the left amygdala and the dorsolateral prefrontal
      cortex (dlPFC) as well as the rostral anterior cingulate cortex (ACC).
      Conjunction analysis suggested shared anxiolysis-dependent inverse co-activations
      in SSRI and placebo responders between the left amygdala-dlPFC and left amygdala
      rostral ACC, and a shared positive co-activation between left amygdala-dorsal
      ACC. We demonstrate that amygdala-frontal co-activation patterns differentiate
      effective from ineffective anxiolytic treatments and that SSRI and placebo
      responders share overlapping neuromodulatory paths that may underlie improved
      emotion regulation and reduced expression of anxiety. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00343707.

PMID- 24666528
TI  - [The resting heart rate].
AB  - Assessment of resting heart rate is frequently performed and is easy, reliable
      and inexpensive. Heart rate is used in many algorithms to assess the prognosis of
      acutely ill patients. Elevated resting heart rate is independently related to the
      development of type 2 diabetes, cardiovascular disease and premature all-cause
      mortality. Adding heart rate to cardiovascular prediction models does not lead to
      improved prediction of vascular events or mortality. Beta blockers and non
      dihydropyridine calcium channel blockers decrease heart rate (and blood pressure)
      and lower the risk of premature mortality in patients with heart failure or
      recent myocardial infarction. In two recent randomised trials, ivabradine
      specifically decreased heart rate (but not blood pressure) and the risk of
      cardiovascular events in patients with heart failure or coronary artery disease,
      decreased left ventricular function and resting heart rate of >= 70 beats/minute.
      Selective heart rate reduction is a potential treatment option to decrease
      cardiovascular risk.

PMID- 24666529
TI  - [Practice guideline 'Diagnosis and treatment of the subacromial pain syndrome'].
AB  - In shoulder pain there is often no direct relationship between the symptoms and
      the anatomical substrate; for this reason, the term 'subacromial pain syndrome'
      (SAPS) is better than 'impingement'. The diagnosis of SAPS can only be made using
      a combination of tests. Imaging diagnostics, preferably ultrasound, can be
      carried out if conservative treatment does not give the required result. Acute
      pain is treated by giving advice and if necessary analgesics; a subacromial
      injection of glucocorticoids is indicated if symptoms recur or are persistent.
      Exercise therapy should be specific, of low intensity and high frequency,
      including eccentric training, scapula stabilization and trigger point massage.
      Rehabilitation in a specialized unit may be considered if pain maintaining
      behaviour is playing a role. There is no convincing evidence that surgical
      treatment is more effective than conservative management and there is no
      indication for the surgical treatment of asymptomatic rotator cuff tears.

PMID- 24666530
TI  - [Contemporary interpretation of lung function test results].
AB  - OBJECTIVE: To determine which changes take place in the interpretation of
      spirometric examination results when the transition is made from reference values
      for children (Zapletal) and adults (European Community for Steel and Coal (ECSC))
      to those from the Global Lung Function Initiative (GLI). DESIGN: Retrospective
      study. METHOD: We analysed spirometric data (forced expiratory volume in 1 s,
      FEV1 and forced vital capacity, FVC) obtained pre- and post-bronchodilation in
      patients: 1012 children (aged 6-17 years, 47.1% girls) and 4653 adults (aged 18
      91 years, 48.6% females). Prevalence rates of airway obstruction based on the
      lower limit of predicted values (FEV1/FVC < 5th percentile) and an abnormally low
      FVC (FEV1/FVC > 0.85, FVC < 5th percentile) were calculated in 9 groups of
      patients. Airway obstruction was also classified based on the Global Initiative
      for Chronic Obstructive Lung Disease (GOLD) criterion: FEV1/FVC < 0.70. RESULTS:
      Predicted values for FEV1 and FVC according to ECSC and Zapletal were too low.
      The prevalence rates of spirometrically determined airway obstruction using the
      three prediction equations varied little; an abnormally low FVC occurred more
      frequently, especially in young adults. GOLD-defined airway obstruction led to
      13.5% underdiagnosis in those aged < 45 years, and about 33% overdiagnosis in
      elderly subjects, being markedly age-dependent. CONCLUSION: The prevalence rate
      of spirometrically determined airway obstruction is little affected by adopting
      the GLI reference values. The GOLD criterion for airway obstruction leads to
      underdiagnosis in adults aged < 45 years, and appreciable overdiagnosis in those
      aged > 45 years. Using z-scores to interpret test results removes biases related
      to age, height and sex and ethnic group and is clinically valid.

PMID- 24666532
TI  - [Recurrent isolated angioedema as a result of acquired C1 inhibitor deficiency].
AB  - Isolated angioedema may be the presenting symptom of acquired C1 inhibitor (C1
      INH) deficiency. C1-INH deficiency is associated with lymphoproliferative
      disorders. Treatment of the underlying disease can result in a complete reversal
      of clinical and complement abnormalities. We describe a 41-year-old woman who was
      referred to our emergency department with recurrent episodes of isolated
      angioedema. Initially, her angioedema was linked to the use of angiotensin
      receptor blockers. However, after discontinuation of this drug angioedema
      recurred. Additional investigations revealed the presence of acquired C1-INH
      deficiency caused by an indolent non-Hodgkin's lymphoma. Treatment with rituximab
      resulted in complete clinical and biochemical remission of the acquired
      angioedema. 

PMID- 24666533
TI  - [The Alice in Wonderland syndrome].
AB  - BACKGROUND: Alice in Wonderland syndrome (AIWS) is characterised by abnormal
      perception, such as metamorphopsia, macropsia, micropsia, teleopsia and pelopsia.
      Although brief and transient, these episodes of visual distortion may lead to
      great anxiety, especially in children. AIWS seems to be associated with specific
      viral infections, epilepsy, migraine, and brain tumours. CASE DESCRIPTION: An 8
      year-old boy had episodes of seeing persons further away than they actually were
      (teleopsia). These perceptual distortions occurred when he was about to go to
      sleep. The episodes never exceeded 10 minutes. He was referred to a paediatrician
      and an ophthalmologist, who found no abnormalities. Serological tests showed a
      positive IgG for both Epstein-Barr and varicella zoster virus. CONCLUSION: The
      cause of AIWS is unclear. When occurring in the young patient, parents often
      become worried. In most cases no serious pathological cause is found. Usually,
      reassurance is sufficient. Therefore, general practitioners should be able to
      recognise the symptoms.

PMID- 24666534
TI  - [Clinical guideline 'Turner syndrome'].
AB  - Turner syndrome occurs in women who are missing one X chromosome. The most
      obvious symptoms are small stature and ovarian failure. Turner patients have an
      increased risk of a large number of disorders, and should therefore have lifelong
      medical supervision. Recent insights into patient management have been
      incorporated into the guidelines. Patients are increasingly involved in their own
      treatment. In patients with 45,X karyotype, Y-chromosomal material is actively
      sought in a larger number of cells and/or other tissues, using FISH. Pubertal
      induction therapy, if required, is initiated at an appropriate age. Egg donation
      or vitrification are new therapeutic options for fertility treatment. Monitoring
      for cardiac and vascular disease using cardiac ultrasound and MRI is performed
      more often, partly in connection with the risk of aortal dissection. The
      coordination of care of patients with Turner syndrome is concentrated in
      specialized centres in the Netherlands and Belgium.

PMID- 24666535
TI  - [Position of guidelines under new law: consequences of new legislation on health
      care quality].
AB  - Recent legislation in the Netherlands has led to the creation of an institute for
      health care quality ('Zorginstituut Nederland'). This institute maintains a
      public register of medical practice guidelines. The legislation does not
      influence the legal position of these guidelines, but may lead to problems with
      regard to the process of developing guidelines, and to the authority of the
      institute to accept guidelines without the full cooperation of the medical
      profession. 

PMID- 24666536
TI  - [Interpretation of spirometry: distinguishing prevalence from function].
AB  - To interpret spirometric data, it helps if (a) we make a distinction between
      prevalence and function; and (b) consider the test result within its clinical
      context. The reference values recently described by the Global Lung Function
      Initiative provide both predicted values and the fifth percentile for a set of
      spirometric parameters. The use of the fifth percentile to distinguish 'normal'
      from 'abnormal' has the advantage that the percentage of healthy subjects who are
      incorrectly classified as 'abnormal' is known. With respect to function, a score
      based on the spread of spirometric parameters in the healthy population does not
      appear to be appropriate. Instead, there are good reasons to evaluate the
      severity of the functional impairment by mapping the lung function parameters on
      a scale from 0 to 100% of the predicted value. 

PMID- 24666538
TI  - Patient participation in hospital care: Nursing staffs' point of view.
AB  - The aim was to investigate nursing staff's perceptions related to patient
      participation and the parameters affecting it during nursing care. A cross
      sectional study with both a quantitative and qualitative orientation was
      conducted. The sample consisted of all nursing staff working in medical and
      surgical wards in three Greek hospitals. A questionnaire was developed and the
      data were analysed with exploratory factor analysis, whereas content analysis was
      used for qualitative data. Nursing staff perceived participation as the process
      of information giving to patients, communication of symptoms by patients and
      compliance with the staff's orders. 'Information providing' and 'ability to
      influence and responsibility' were significant aspects of the content of
      participation, whereas the parameters affecting participation were related to
      patients, nursing staff and the care context. These results support patient
      engagement in dialogue and shared decision-making, while highlighting the need to
      implement participation systematically and stimulate changes in nursing care
      organization. 

PMID- 24666539
TI  - Students' experiences of school suspension.
AB  - ISSUE ADDRESSED: School inclusion and academic attainment are key social
      determinants of health. Students who have been suspended from school are more
      likely to disengage from school and consequently not receive the health promoting
      benefits of social inclusion and academic achievement. This study sought to
      explore the experiences of students who have been previously suspended (i.e. had
      experienced school exclusion). METHODS: Seventy-four previously suspended
      adolescents from five schools in the state of Victoria, Australia, completed a
      written questionnaire. Students reported their understanding of the process of
      being suspended; what they did and with whom they spent the day(s) of suspension;
      and their perceptions of their return to school post-suspension. RESULTS: While
      suspended, a minority of suspended students received adult supervision and most
      suspended students participated in benign leisure activities. Upon return to
      school, students reported diminished teacher assistance and found that suspension
      did not help resolve the underlying issues that lead to the suspension.
      CONCLUSIONS: Removal of a student displaying problem behaviours from the
      classroom may provide temporary relief to the school community but suspended
      students report minimal benefits from suspension. Suspension removes the
      potential pro-social normative influences of school and provides an opportunity
      to establish antisocial peer networks. Suspended students appear to perceive a
      stigma upon their return to school, further diminishing an already tenuous school
      relationship. So what? School suspension exposes disadvantaged students to
      several negative social determinants of health. Students displaying problem
      behaviours would benefit from interventions that maintain the student's
      relationship with school. Should suspension be necessary, schools could assist by
      ensuring that suspended students receive appropriate adult supervision and a
      formal reintegration to school to promote social inclusion and academic
      attainment, two recognised key determinants of health.

PMID- 24666537
TI  - Physiological responses to food intake throughout the day.
AB  - Circadian rhythms act to optimise many aspects of our biology and thereby ensure
      that physiological processes are occurring at the most appropriate time. The
      importance of this temporal control is demonstrated by the strong associations
      between circadian disruption, morbidity and disease pathology. There is now a
      wealth of evidence linking the circadian timing system to metabolic physiology
      and nutrition. Relationships between these processes are often reciprocal, such
      that the circadian system drives temporal changes in metabolic pathways and
      changes in metabolic/nutritional status alter core molecular components of
      circadian rhythms. Examples of metabolic rhythms include daily changes in glucose
      homeostasis, insulin sensitivity and postprandial response. Time of day alters
      lipid and glucose profiles following individual meals whereas, over a longer time
      scale, meal timing regulates adiposity and body weight; these changes may occur
      via the ability of timed feeding to synchronise local circadian rhythms in
      metabolically active tissues. Much of the work in this research field has
      utilised animal and cellular model systems. Although these studies are highly
      informative and persuasive, there is a largely unmet need to translate basic
      biological data to humans. The results of such translational studies may open up
      possibilities for using timed dietary manipulations to help restore circadian
      synchrony and downstream physiology. Given the large number of individuals with
      disrupted rhythms due to, for example, shift work, jet-lag, sleep disorders and
      blindness, such dietary manipulations could provide widespread improvements in
      health and also economic performance. 

PMID- 24666541
TI  - Loss of contrast enhancement of the inferior rectus muscle on magnetic resonance
      imaging in acute fulminant invasive fungal sinusitis.

PMID- 24666540
TI  - Regenerative defect in vastus lateralis muscle of patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Impaired skeletal muscle regeneration could contribute to the
      progression of muscle atrophy in patients with chronic obstructive pulmonary
      disease (COPD). METHODS: Satellite cells and myogenesis-related proteins were
      compared between healthy subjects and patients with COPD, with or without muscle
      atrophy. Satellite cells were isolated and cultured to assess their proliferative
      and differentiation aptitudes. RESULTS: Although satellite cell numbers in muscle
      samples were similar between groups, the proportion of muscle fibers with central
      nuclei was increased in COPD. In muscle homogenates, increased expression of MyoD
      and decreased expression of myogenin and MRF4 were observed in COPD. In cultured
      satellite cells of patients with COPD, increased protein content was observed for
      Pax7, Myf5 (proliferation phase) and myogenin (differentiation phase) while
      myosin heavy chain protein content was significantly lower during
      differentiation. CONCLUSION: In COPD, the number of central nuclei was increased
      in muscle fibers suggesting a greater number of attempts to regenerate muscle
      tissue than in healthy subjects. Myogenesis signaling was also altered in muscle
      homogenates in patients with COPD and there was a profound reduction in the
      differentiation potential in this population as indicated by a reduced ability to
      incorporate myosin heavy chain into newly formed myotubes. Collectively, these
      results indicate that skeletal muscle regenerative capacity termination is
      impaired in COPD and could contribute to the progression of muscle atrophy
      progression in this population.

PMID- 24666542
TI  - Cognitive dysfunction following desflurane versus sevoflurane general anesthesia
      in elderly patients: a randomized controlled trial.
AB  - As life expectancy increases, more patients >=65 years undergo general
      anesthesia. Anesthetic agents may contribute to postoperative cognitive
      dysfunction, and incidence may differ with anesthetic agents or intraoperative
      anesthesia depth. Responses to anesthetic adjuvants vary among elderly patients.
      Processed electroencephalography guidance of anesthetic may better ensure
      equivalent cerebral suppression. This study investigates postoperative cognitive
      dysfunction differences in elderly patients given desflurane or sevoflurane using
      processed electroencephalography guidance.IRB approved, randomized trial enrolled
      consenting patients >=65 years scheduled for elective surgery requiring general
      anesthesia >=120 minute duration. After written informed consent, patients were
      randomly assigned to sevoflurane or desflurane. No perioperative benzodiazepines
      were administered. Cognitive impairment was measured by an investigator blinded
      to group assignment using mini-Mental Status Examination (MMSE) at baseline; 1,
      6, and 24 hours after the end of anesthesia. Mean arterial pressure was
      maintained within 20% of baseline. Anesthetic dose was adjusted to maintain
      moderate general anesthesia per processed electroencephalograpy (Patient State
      Index 25 to 50). The primary outcome measure was intergroup difference in MMSE
      change 1 hour after anesthesia (median; 95% confidence interval).110 patients
      consented; 26 were not included for analysis (no general anesthesia; withdrew
      consent; baseline MMSE abnormality; inability to perform postoperative MMSE; data
      capture failure); 47 sevoflurane and 37 desflurane were analyzed. There were no
      significant differences in patient characteristics; intraoperative mean blood
      pressure (desflurane 86.4; 81.3 to 89.6 versus sevoflurane 82.5; 80.2 to 86.1
      mmHg; p = 0.42) or Patient State Index (desflurane 41.9; 39.0 to 44.0 versus
      sevoflurane 41.0; 37.5 to 44.0; p = 0.60) despite a lower MAC fraction in
      desflurane (0.82; 0.77 to 0.86) versus sevoflurane (0.96; 0.91 to 1.03; p <
      0.001). MMSE decreased 1 hour after anesthesia (p < 0.001). The decrease at one
      hour was larger in sevoflurane (-2.5; -3.3 to -1.8) than desflurane (-1.3; -2.2
      to -0.5; p = 0.03). MMSE returned to baseline by 6 hours after anesthesia.
      CONCLUSIONS: For elderly patients in whom depth of anesthesia is maintained in
      the moderate range, both desflurane and sevoflurane are associated with transient
      decreases in cognitive function as measured by MMSE after anesthesia, with
      clinically insignificant differences between them in this setting. TRIAL
      REGISTRY: ClinicalTrials.gov NCT01199913.

PMID- 24666543
TI  - Protection and pathology during parasite infection: IL-10 strikes the balance.
AB  - The host response to infection requires an immune response to be strong enough to
      control the pathogen but also restrained, to minimize immune-mediated pathology.
      The conflicting pressures of immune activation and immune suppression are
      particularly apparent in parasite infections, where co-evolution of host and
      pathogen has selected many different compromises between protection and
      pathology. Cytokine signals are critical determinants of both protective immunity
      and immunopathology, and, in this review, we focus on the regulatory cytokine IL
      10 and its role in protozoan and helminth infections. We discuss the sources and
      targets of IL-10 during parasite infection, the signals that initiate and
      reinforce its action, and its impact on the invading parasite, on the host
      tissue, and on coincident immune responses. 

PMID- 24666544
TI  - Examining and addressing evidence-practice gaps in cancer care: a systematic
      review.
AB  - BACKGROUND: There is increasing recognition of gaps between best scientific
      evidence and clinical practice. This systematic review aimed to assess the volume
      and scope of peer-reviewed cancer research output in the years 2000, 2005, and
      2010. METHODS: Eligible papers were published in English and reported on evidence
      practice gaps in cancer care. The electronic database Medline was searched for
      three time periods using MeSH headings and keywords. Abstracts were assessed
      against eligibility criteria by one reviewer and checked by a second. Papers
      meeting eligibility criteria were coded as data-based or non-data-based, and by
      cancer type of focus. All data-based papers were then further classified as
      descriptive studies documenting the extent of, or barriers to addressing, the
      evidence-practice gap; or intervention studies examining the effectiveness of
      strategies to reduce the evidence-practice gap. RESULTS: A total of 176 eligible
      papers were identified. The number of publications significantly increased over
      time, from 25 in 2000 to 100 in 2010 (p < 0.001). Of the 176 identified papers,
      160 were data-based. The majority of these (n = 150) reported descriptive
      studies. Only 10 studies examined the effectiveness of interventions designed to
      reduce discrepancies between evidence and clinical practice. Of these, only one
      was a randomized controlled trial. Of all data-based studies, almost one-third (n
      = 48) examined breast cancer care. CONCLUSIONS: While the number of publications
      investigating evidence-practice gaps in cancer care increased over a ten-year
      period, most studies continued to describe gaps between best evidence and
      clinical practice, rather than rigorously testing interventions to reduce the
      gap.

PMID- 24666545
TI  - Clinical characteristics of basilar-type migraine in the neurological clinic of a
      university hospital.
AB  - OBJECTIVES: The aim of this study was to investigate the prevalence and clinical
      characteristics of basilar-type migraine in the neurology outpatient clinic of a
      university hospital in China. METHODS: This cross-sectional study was conducted
      in the neurology outpatient of a tertiary care hospital in Chongqing between
      January 2010 and December 2011. All consecutive patients citing headache as their
      chief complaint were asked to complete a face-to-face interview by a qualified
      headache specialist using a detailed questionnaire for headache. The diagnosis of
      basilar-type migraine was made according to International Classification of
      Headache Disorders Second Edition. RESULTS: Of the 1,526 headache patients, 23
      (1.5%) were diagnosed with basilar-type migraine (19 women, four men). Basilar
      type migraine occurred in 6.6% (23/348) of patients with migraine with
      nonhemiplegic aura. Mean age at onset was 20.3 +/- 11.7 years (range 6-49 years).
      Among these patients, 65% (15/23) reported bilateral pain, 35% (8/23) unilateral
      pain. The basilar-type aura comprised diplopia 52%, vertigo 43%, tinnitus 43%,
      bilateral visual symptoms 39%, hypacusia 26%, ataxia 26%, dysarthria 22%,
      bilateral paresthesias 13%, and decreased level of consciousness 13%. Intense
      emotional stimuli (74%) and sleep disorders (65%) were the most common trigger
      factors, followed by change in weather, sunshine, cold wind, acute stress,
      alcohol, and fatigue. CONCLUSION: Basilar-type migraine is an episodic disorder
      and occurred in 1.5% of patients with headache. More than one-half of patients
      have their first attack in the second and third decade of life. Trigger factors
      were common, and patients should be educated to avoid trigger factors.

PMID- 24666546
TI  - Exploring intentions to discriminate against patients living with HIV/AIDS among
      future healthcare providers in Malaysia.
AB  - OBJECTIVES: Stigma towards people living with HIV/AIDS (PLWHA) is strong in
      Malaysia. Although stigma has been understudied, it may be a barrier to treating
      the approximately 81 000 Malaysian PLWHA. The current study explores correlates
      of intentions to discriminate against PLWHA among medical and dental students,
      the future healthcare providers of Malaysia. METHODS: An online, cross-sectional
      survey of 1296 medical and dental students was conducted in 2012 at seven
      Malaysian universities; 1165 (89.9%) completed the survey and were analysed.
      Socio-demographic characteristics, stigma-related constructs and intentions to
      discriminate against PLWHA were measured. Linear mixed models were conducted,
      controlling for clustering by university. RESULTS: The final multivariate model
      demonstrated that students who intended to discriminate more against PLWHA were
      female, less advanced in their training, and studying dentistry. They further
      endorsed more negative attitudes towards PLWHA, internalised greater HIV-related
      shame, reported more HIV-related fear and disagreed more strongly that PLWHA
      deserve good care. The final model accounted for 38% of the variance in
      discrimination intent, with 10% accounted for by socio-demographic
      characteristics and 28% accounted for by stigma-related constructs. CONCLUSIONS:
      It is critical to reduce stigma among medical and dental students to eliminate
      intentions to discriminate and achieve equitable care for Malaysian PLWHA. Stigma
      reduction interventions should be multipronged, addressing attitudes,
      internalised shame, fear and perceptions of deservingness of care.

PMID- 24666547
TI  - Exercise-induced bronchospasm related to different phenotypes of rhinitis without
      asthma in primary schoolchildren: the French Six Cities Study.
AB  - BACKGROUND: Exercise-induced bronchospasm (EIB) is frequent among asthmatic
      children. However, opinions differ on the relation between EIB and rhinitis in
      the absence of asthma. OBJECTIVES: We assessed the relationship between EIB and
      various phenotypes of rhinitis according to asthmatic status at the general
      population level in the Six Cities Study. METHODS: Of 7781 schoolchildren with a
      mean age of 10 years underwent an EIB test and skin prick test to assess allergic
      sensitization. Their parents completed a standardized questionnaire recording
      asthma-like symptoms and past-year rhinoconjunctivitis, ever hay fever (EHF), and
      a score for allergic rhinitis (SFAR) >=7 as a marker of 'past-year allergic
      rhinitis'. Exercise-induced bronchospasm was defined as a fall in peak expiratory
      flow rate >=15% after exercise. RESULTS: Of the 6813 schoolchildren retained for
      analysis, 227 (3.33%) experienced EIB after exercise. Odds ratios [95% confidence
      intervals] between EIB and allergic rhinitis phenotypes in the absence of asthma
      were 1.56 [0.92-2.63] for EHF, 1.97 [1.16-3.35] for past-year
      rhinoconjunctivitis, and 1.84 [1.16-2.91] for a SFAR >=7. Results were unchanged
      after adjustment for confounders. Multiple correspondence analysis showed that
      EIB, although related to asthma, constitutes a separate entity. Exercise-induced
      bronchospasm was not significantly related to familial history of asthma.
      CONCLUSION: In our large population-based sample of children, different
      phenotypes of atopic rhinitis were associated with EIB, independently of asthma.
      Exercise-induced bronchospasm, although related to asthma, seems to constitute a
      separate entity. CLINICAL RELEVANCE: In this large (6813) sample of 10-year
      children drawn from the general population, EIB is associated with rhinitis
      phenotypes in the absence of asthma. Furthermore, it constitutes an entity
      independent from asthma and is not related to a familial history of asthma. Thus,
      investigating these symptoms could be important in this disease, as a specific
      nasal treatment might improve EIB in these children.

PMID- 24666548
TI  - The impact of COX-2 on invasion of osteosarcoma cell and its mechanism of
      regulation.
AB  - BACKGROUND: Recently, cyclooxygenase-2 (COX-2) has become an important new target
      in the field of tumor metastasis. However, the relationship between COX-2 gene
      expression and the behavior of osteosarcoma metastasis is largely unknown. The
      study is to investigate how antisense oligonucleotides (ODNs) of COX-2 inhibit
      the invasion of human osteosarcoma cell line OS-732 and their mechanism of
      regulation. METHODS: A COX-2 antisense oligonucleotide was designed, synthesized,
      and transfected into OS-732 human osteosarcoma cells. RT-PCR and western blotting
      were performed to determine the transfection efficiency. A modified Boyden
      transwell assay was used to measure the inhibition rate of tumor cell invasion.
      In OS-732 cells transfected with COX-2 antisense ODNs, RT-PCR was used to examine
      the mRNA expression of urokinase-type plasminogen activator (uPA) and that of its
      receptor, uPAR. RESULTS: Both the mRNA and protein expression levels of COX-2
      were significantly reduced when cells were transfected with COX-2 antisense ODNs,
      which significantly reduced the invasive ability of OS-732 cells in a dose
      dependent manner. The expression levels of uPA and uPAR were also significantly
      reduced (p < 0.01). CONCLUSION: COX-2 antisense ODNs significantly inhibited the
      invasion of OS-732 cells, primarily by decreasing the mRNA expression of uPA and
      uPAR.

PMID- 24666549
TI  - Cross-sectional study of attitudes about suicide among psychiatrists in Shanghai.
AB  - BACKGROUND: Attitudes and knowledge about suicide may influence psychiatrists'
      management of suicidal patients but there has been little research about this
      issue in China. METHODS: We used the Scale of Public Attitudes about Suicide
      (SPAS)--a 47-item scale developed and validated in China--to assess knowledge
      about suicide and seven specific attitudes about suicide in a sample of 187
      psychiatrists from six psychiatric hospitals in Shanghai. The results were
      compared to those of 548 urban community members (assessed in a previous study).
      RESULTS: Compared to urban community members, psychiatrists were more likely to
      believe that suicide can be prevented and that suicide is an important social
      problem but they had more stigmatizing beliefs about suicidal individuals and
      felt less empathy for them. The belief that suicide can be prevented was more
      common among female psychiatrists than male psychiatrists but male psychiatrists
      felt more empathy for suicidal individuals. Only 37% of the psychiatrists
      correctly agreed that talking about suicide-related issues with an individual
      would not precipitate suicidal behavior and only 41% correctly agreed that those
      who state that they intend to kill themselves may actually do so. CONCLUSIONS:
      Many psychiatrists in Shanghai harbor negative attitudes about suicidal
      individuals and are concerned that directly addressing the issue with patients
      will increase the risk of suicide. Demographic factors, educational status and
      work experience are associated with psychiatrists' attitudes about suicide and,
      thus, need to be considered when training psychiatrists about suicide prevention.

PMID- 24666550
TI  - Significant benefits after renal transplantation in patients with chronic heart
      failure and chronic kidney disease.
AB  - BACKGROUND: Chronic heart failure (CHF) and chronic kidney disease (CKD) are
      serious medical conditions with significant morbidity and mortality and often
      coexist. Because of perioperative risks in these patients, they may not be
      considered a candidate for renal transplantation (RTx). MATERIAL AND METHODS: We
      compare retrospectively RTx outcomes [graft/patient survival, rejection rates and
      adverse cardiac events] in study group [low left ventricular ejection fraction
      (LVEF) <= 45% by echocardiogram, n = 63] and control group [normal LVEF >= 50%, n
      = 537] from a developing country. RESULTS: The mean EF was 35 +/- 5.6 and 57 +/-
      3% for the study and control groups, respectively (p < 0.001). Majority of these
      patients (98%) showed normalization of LVEF post-transplant. The median EF was
      60% at 1-3 months post-transplant. No difference was noted in graft survival,
      patient survival, rejection rates, serum creatinine and adverse cardiac events of
      study group at 1.3-year mean follow-up compared to control group. Outcome was not
      adversely affected by preexisting LV dysfunction. The study and control groups
      had nearly similar percent of patients with established CAD but significantly
      more hospitalization for CHF pre RTx in the study group compared with the control
      group. CONCLUSION: RTx may play a role in reversing LV systolic dysfunction. Once
      thought by many to be a contraindication for renal transplantation, this appears
      not to be the case. The outcomes between the 2 groups are comparable and
      transplant is an option for even low EF patients.

PMID- 24666551
TI  - Prevalence of metabolic syndrome and cardiovascular risk level in a vulnerable
      population.
AB  - This study examined the prevalence of metabolic syndrome and the risk level of
      cardiovascular disease (CVD) in a vulnerable population of 407 subjects in Korea.
      This descriptive study was a part of the Tailed Health Visiting Service Program,
      using baseline data from public health centres in Suwon, Korea. The definition of
      metabolic syndrome was based on the National Cholesterol Education Program
      criteria, and risk of CVD was estimated according to the Framingham study
      equation. This study demonstrated that the prevalence of metabolic syndrome was
      40.8% higher and the risk of CVD was significantly 3.1 times higher among those
      with metabolic syndrome than among those without it. Of those with metabolic
      syndrome, 50.6% overall and 81.1% of men had a high risk for CVD. These findings
      suggest a need to screen and prevent the risk of CVD in vulnerable populations
      with metabolic syndrome. 

PMID- 24666552
TI  - Short term micronutrient-antioxidant supplementation has no impact on a
      serological marker of gastric atrophy in Zambian adults: retrospective analysis
      of a randomised controlled trial.
AB  - BACKGROUND: Gastric cancer is a major contributor to cancer deaths in Zambia but,
      as elsewhere, no preventive strategies have been identified. We set out to
      investigate the possibility of reducing gastric atrophy, a premalignant lesion,
      using micronutrient-antioxidant supplementation. METHODS: We analysed 215
      archival samples from a randomised controlled trial of micronutrient-antioxidant
      supplementation carried out from 2003 to 2006. Participants were randomised to
      receive either the supplement or placebo and had been taking the allocated
      intervention for a mean of 18 (range 14-27) months when the samples used in this
      study were taken. We used low pepsinogen 1 to 2 (PEP1:2) ratio as a surrogate
      marker of gastric atrophy. A PEP 1:2 ratio of less than three was considered low.
      HIV serology, age, nutritional status, smoking, alcohol intake and gastric pH
      were also analysed. Ethical approval was obtained from the University of Zambia
      Biomedical Research Ethics Committee (011-04-12). The randomized trial was
      registered (ISRCTN31173864). RESULTS: The overall prevalence of low PEP 1:2 ratio
      was 15/215 (7%) and it did not differ between the placebo (8/103, 7.8%) and
      micronutrient groups (7/112, 6.3%; HR 1.24; 95% CI 0.47-3.3; P = 0.79). The
      presence of low PEP 1:2 ratio was not influenced by HIV infection (HR 1.07; 95%
      CI 0.37-3.2; P =0.89) or nutritional status but it inversely correlated with
      gastric pH (Spearman's rho = -0.34; P = 0.0001). Age above 40 years was
      associated with atrophy, but neither alcohol nor smoking had any influence.
      CONCLUSION: Short term micronutrient supplementation does not have any impact on
      PEP 1:2 ratio, a serological marker of gastric atrophy. PEP 1:2 ratio inversely
      correlates with gastric pH.

PMID- 24666554
TI  - Association between dietary carbohydrate intake quality and micronutrient intake
      adequacy in a Mediterranean cohort: the SUN (Seguimiento Universidad de Navarra)
      Project.
AB  - Epidemiological research confirms that the prevalence of suboptimal micronutrient
      intakes across Europe is an emerging concern in terms of public health. The aim
      of the present study was to investigate the association between a new index of
      carbohydrate (CHO) quality and micronutrient intake adequacy in the 'Seguimiento
      Universidad de Navarra (SUN)' cohort. The baseline assessment extended from 1999
      to March 2012. We assessed 16,841 participants who completed a validated 136-item
      semi-quantitative FFQ at baseline. We created a new index to evaluate CHO quality
      for the following four criteria: dietary fibre intake; glycaemic index; whole
      grains:total grains ratio; solid CHO:total CHO ratio. The subjects were
      classified into quintiles according to this index. We evaluated the intakes of
      Zn, I, Se, Fe, Ca, K, P, Mg, Cr and vitamins B1, B2, B3, B6, B12, C, A, D, E and
      folic acid. The probability of intake adequacy was evaluated using the estimated
      average requirement cut-point approach and the probabilistic approach. Logistic
      regression analysis was used to assess the nutritional adequacy according to the
      CHO quality index (CQI). Participants in the highest quintile of CQI were found
      to have the lowest prevalence of inadequacy. A higher quality of CHO intake was
      found to be associated with a lower risk of nutritional inadequacy in comparison
      with the lowest quintile of CQI (adjusted OR 0.06, 95 % CI 0.02, 0.16; P for
      trend < 0.001). A higher CQI was found to be strongly associated with better
      micronutrient intake adequacy in the young Mediterranean cohort, stressing the
      importance of focusing nutritional education not only on CHO quantity, but also
      on quality.

PMID- 24666555
TI  - Teachers' perspectives of supporting pupils with long-term health conditions in
      mainstream schools: a narrative review of the literature.
AB  - Teachers are supporting an increasing number of pupils with long-term health
      conditions in mainstream schools. The aim of this literature review was to
      critically appraise and synthesise research that has examined teachers'
      perceptions of the key barriers and facilitators to supporting pupils with long
      term conditions, teachers' training needs and interventions that aim to improve
      teachers' knowledge of long-term conditions, and teachers' confidence in
      supporting children and young people. A narrative literature review was conducted
      using a systematic search of computerised databases and manual searches of key
      journals and reference lists to retrieve studies published between 2003 and 2013.
      Studies were critically appraised and key themes across studies identified. In
      total, 61 papers from 58 studies were included in the review. The findings
      suggest that teachers receive little formal training relevant to long-term
      condition management and are fearful of the risks involved in teaching children
      and young people with long-term conditions. Communication between families,
      school and health and social care services appears to be poor. Educational
      programmes developed in conjunction with and/or delivered by healthcare
      professionals seem to have the potential to increase teachers' knowledge and
      confidence. This review suggests that healthcare professionals have an important
      role to play in supporting teachers in identifying and meeting the needs of
      pupils with long-term conditions. It is vital that pupils with long-term
      conditions receive appropriate care and support in schools to ensure their safety
      and help them to integrate with their peers and achieve their academic potential.
      Limitations in the current evidence are highlighted and implications for future
      research are identified. 

PMID- 24666553
TI  - Misconceptions about fructose-containing sugars and their role in the obesity
      epidemic.
AB  - A causal role of fructose intake in the aetiology of the global obesity epidemic
      has been proposed in recent years. This proposition, however, rests on
      controversial interpretations of two distinct lines of research. On one hand, in
      mechanistic intervention studies, detrimental metabolic effects have been
      observed after excessive isolated fructose intakes in animals and human subjects.
      On the other hand, food disappearance data indicate that fructose consumption
      from added sugars has increased over the past decades and paralleled the increase
      in obesity. Both lines of research are presently insufficient to demonstrate a
      causal role of fructose in metabolic diseases, however. Most mechanistic
      intervention studies were performed on subjects fed large amounts of pure
      fructose, while fructose is ordinarily ingested together with glucose. The use of
      food disappearance data does not accurately reflect food consumption, and hence
      cannot be used as evidence of a causal link between fructose intake and obesity.
      Based on a thorough review of the literature, we demonstrate that fructose, as
      commonly consumed in mixed carbohydrate sources, does not exert specific
      metabolic effects that can account for an increase in body weight. Consequently,
      public health recommendations and policies aiming at reducing fructose
      consumption only, without additional diet and lifestyle targets, would be
      disputable and impractical. Although the available evidence indicates that the
      consumption of sugar-sweetened beverages is associated with body-weight gain, and
      it may be that fructose is among the main constituents of these beverages, energy
      overconsumption is much more important to consider in terms of the obesity
      epidemic. 

PMID- 24666556
TI  - Socio-economic inequalities in patient, primary care, referral, diagnostic, and
      treatment intervals on the lung cancer care pathway: protocol for a systematic
      review and meta-analysis.
AB  - BACKGROUND: Early diagnosis and treatment of cancer is thought to be important
      for improving survival. Longer time between the onset of cancer symptoms and
      receipt of treatment may help explain the poorer survival of UK cancer patients
      compared to that in other countries.Socio-economic inequalities in receipt of,
      and time to, treatment may contribute to socio-economic differences in cancer
      survival. Socio-economic inequalities in receipt of lung cancer treatment have
      been shown in a recent systematic review. However, no systematic review of the
      evidence for socio-economic inequalities in time to presentation (patient
      interval), time to first investigation (primary care interval), time to secondary
      care investigation (referral interval), time to diagnosis (diagnostic interval),
      and time to treatment (treatment interval) has been conducted.This review aims to
      assess the published and grey literature evidence for socio-economic inequalities
      in the length of time spent on the lung cancer diagnostic and treatment pathway,
      examining interim intervals on the pathway where inequalities might occur.
      METHODS: Systematic methods will be used to identify relevant studies, assess
      study eligibility for inclusion, and evaluate study quality. The online databases
      of MEDLINE, EMBASE, and CINAHL will be searched to locate cohort studies of
      adults with a primary diagnosis of lung cancer; where the outcome is mean or
      median time to the interval endpoint (or a suitable proxy measure of this), or
      the likelihood of longer or shorter time to the endpoint; analysed by a measure
      of socio-economic position. Meta-analysis will be conducted if there are
      sufficient studies available with suitable data. DISCUSSION: This review will
      systematically determine if there are socio-economic inequalities in time from
      symptom onset to treatment for lung cancer. If such inequalities are present, our
      review evidence will help inform the development of interventions to reduce the
      time to diagnosis and treatment, ultimately helping to reduce socio-economic
      inequalities in survival. TRIAL REGISTRATION: PROSPERO CRD42014007145.

PMID- 24666557
TI  - Closing the chasm between research and practice: evidence of and for change.
AB  - The usual remedy suggested for bridging the science-to-practice gap is to improve
      the efficiency of disseminating the evidence-based practices to practitioners.
      This reflection on the gap takes the position that it is the relevance and fit of
      the evidence with the majority of practices that limit its applicability and
      application in health promotion and related behavioural, community and population
      level interventions where variations in context, values and norms make uniform
      interventions inappropriate. To make the evidence more relevant and actionable to
      practice settings and populations will require reforms at many points in the
      research-to-practice pipeline. These points in the pipeline are described and
      remedies for them suggested. 

PMID- 24666559
TI  - False belief in infancy: a fresh look.
AB  - Can infants appreciate that others have false beliefs? Do they have a theory of
      mind? In this article I provide a detailed review of more than 20 experiments
      that have addressed these questions, and offered an affirmative answer, using
      nonverbal 'violation of expectation' and 'anticipatory looking' procedures.
      Although many of these experiments are both elegant and ingenious, I argue that
      their results can be explained by the operation of domain-general processes and
      in terms of 'low-level novelty'. This hypothesis suggests that the infants'
      looking behaviour is a function of the degree to which the observed (perceptual
      novelty) and remembered or expected (imaginal novelty) low-level properties of
      the test stimuli - their colours, shapes and movements - are novel with respect
      to events encoded by the infants earlier in the experiment. If the low-level
      novelty hypothesis is correct, research on false belief in infancy currently
      falls short of demonstrating that infants have even an implicit theory of mind.
      However, I suggest that the use of two experimental strategies - inanimate
      control procedures, and self-informed belief induction - could be used in
      combination with existing methods to bring us much closer to understanding the
      evolutionary and developmental origins of theory of mind. 

PMID- 24666558
TI  - A randomized clinical trial to assess the influence of a three months training
      program (gym-based individualized vs. calisthenics-based non-invidualized) in
      COPD-patients.
AB  - INTRODUCTION: Pulmonary rehabilitation has been demonstrated to improve exercise
      capacity, dyspnoea, quality of life and to reduce the adverse effects of acute
      exacerbations. Current guidelines recommend exercise training in patients with
      mild to very severe disease. However, there is insufficient data comparing the
      efficacy of different training approaches and intensities. METHODS: Between
      January 2009 and December 2012, 105 COPD patients were screened to participate in
      the study. 61 patients were randomly assigned into an individualized training
      group or into a non-individualized training group. Both groups exercised once a
      week for 60 minutes over a time period of three months. At the beginning and
      after three months, the following measurements were performed: 6-minute walking
      test (6-MWT), health-related quality of life (St. Georges Respiratory
      Questionnaire; SGRQ and COPD-Assessment-Test; CAT), M. rectus femoris cross
      sectional area, and inflammatory markers in peripheral blood. RESULTS: Only in
      the individualized training group we observed a significant change of the 6-MWT
      (increase of 32.47 m; p = 0.012) and the cross-sectional area of the M. rectus
      fermoris (increase of 0.57 cm2; p = 0.049), while no significant changes occurred
      in the non-individualized training group. Peroxisome-proliferator-activated
      receptor-gamma coactivator 1alpha increased in the individualized training only
      after the three months training period (increase of 0.43 relative copies; p =
      0.017), all other myokines and inflammatory markers were not influenced by either
      of the programs. The total drop-out-rate was 44.3%. CONCLUSION: A low frequency
      outpatient training program may induce modest improvements in exercise capacity
      and muscle mass only if it is performed on an individualized basis.

PMID- 24666560
TI  - Changes in pain perception after pelvis manipulation in women with primary
      dysmenorrhea: a randomized controlled trial.
AB  - OBJECTIVE: This study aims to evaluate the immediate effect of a global pelvic
      manipulation (GPM) technique, bilaterally applied, on low back pelvic pain in
      women with primary dysmenorrhea (PD). DESIGN: A prospective, randomized, double
      blind, controlled trial. SETTING: Faculty of Nursing, Physiotherapy and Podiatry.
      University of Sevilla, Spain. METHODS: The sample group included 40 women (30 +/-
      6.10 years) that were divided into an experimental group (EG) (N = 20) who
      underwent a bilateral GPM technique and a control group (CG) (N = 20) who
      underwent a sham (placebo) intervention. Evaluations were made of self-reported
      low back pelvic pain (visual analog scale), pressure pain threshold (PPT) in
      sacroiliac joints (SIJs), and the endogenous response of the organism to pain
      following catecholamines and serotonin release in blood levels. RESULTS: The
      intragroup comparison showed a significant improvement in the EG in the self
      perceived low back pelvic pain (P = 0.003) and in the mechanosensitivity in both
      SIJs (P = 0.001). In the between-group comparison, there was a decrease in pain
      perception (P = 0.004; F(1,38) = 9.62; R(2) = 0.20) and an increase in the PPT of
      both SIJs, in the right side (P = 0.001; F(1,38) = 21.29; R(2) = 0.35) and in the
      left side (P = 0.001; F(1,38) = 20.63; R(2) = 0.35). There were no intergroup
      differences for catecholamines plasma levels (adrenaline P = 0.123; noradrenaline
      P = 0.281; dopamine P = 0.173), but there were for serotonin levels (P = 0.045;
      F(1,38) = 4.296; R(2) = 0.10). CONCLUSION: The bilateral GPM technique improves
      in a short term the self-perceived low back pelvic pain, the PPT in both SIJs,
      and the serotonin levels in women with PD. It shows no significant differences
      with a sham intervention in catecholamines plasma levels.

PMID- 24666561
TI  - Factors influencing the implementation of integrated management of childhood
      illness (IMCI) by healthcare workers at public health centers & dispensaries in
      Mwanza, Tanzania.
AB  - BACKGROUND: Integrated Management of Childhood Illness (IMCI) was developed by
      the World Health Organization (WHO) and the United Nations International
      Children's Fund (UNICEF) and aims at reducing childhood morbidity and mortality
      in resource-limited settings including Tanzania. It was introduced in 1996 and
      has been scaled up in all districts in the country. The purpose of this study was
      to identify factors influencing the implementation of IMCI in the health
      facilities in Mwanza, Tanzania since reports indicates that the guidelines are
      not full adhered to by the healthcare workers. METHODS: A cross-sectional study
      design was used and a sample size of 95 healthcare workers drawn from health
      centers and dispensaries within Mwanza city were interviewed using self
      administered questionnaires. Structured interview was also used to get views from
      the city IMCI focal person and the 2 facilitators. Data were analyzed using SPSS
      and presented using figures and tables. RESULTS: Only 51% of healthcare workers
      interviewed had been trained. 69% of trained Healthcare workers expressed
      understanding of the IMCI approach. Most of the respondents (77%) had a positive
      attitude that IMCI approach was a better approach in managing common childhood
      illnesses especially with the reality of resource constraint in the health
      facilities. The main challenges identified in the implementation of IMCI are low
      initial training coverage among health care workers, lack of essential drugs and
      supplies, lack of onsite mentoring and lack of refresher courses and regular
      supportive supervision. Supporting the healthcare workers through training,
      onsite mentoring, supportive supervision and strengthening the healthcare system
      through increasing access to essential medicines, vaccines, strengthening supply
      chain management, increasing healthcare financing, improving leadership &
      management were the major interventions that could assist in IMCI implementation.
      CONCLUSIONS: The healthcare workers can implement better IMCI through the
      collaboration of supervisors, IMCI focal person, Council Health Management Teams
      (CHMT) and other stakeholders interested in child health. However, significant
      barriers impede a sustainable IMCI implementation. Recommendations have been made
      related to supportive supervision and HealthCare system strengthening among
      others.

PMID- 24666563
TI  - Plant DNA barcoding: from gene to genome.
AB  - DNA barcoding is currently a widely used and effective tool that enables rapid
      and accurate identification of plant species; however, none of the available loci
      work across all species. Because single-locus DNA barcodes lack adequate
      variations in closely related taxa, recent barcoding studies have placed high
      emphasis on the use of whole-chloroplast genome sequences which are now more
      readily available as a consequence of improving sequencing technologies. While
      chloroplast genome sequencing can already deliver a reliable barcode for accurate
      plant identification it is not yet resource-effective and does not yet offer the
      speed of analysis provided by single-locus barcodes to unspecialized laboratory
      facilities. Here, we review the development of candidate barcodes and discuss the
      feasibility of using the chloroplast genome as a super-barcode. We advocate a new
      approach for DNA barcoding that, for selected groups of taxa, combines the best
      use of single-locus barcodes and super-barcodes for efficient plant
      identification. Specific barcodes might enhance our ability to distinguish
      closely related plants at the species and population levels. 

PMID- 24666562
TI  - Plasmodium falciparum clearance in clinical studies of artesunate-amodiaquine and
      comparator treatments in sub-Saharan Africa, 1999-2009.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) is the recommended first
      line therapy for uncomplicated Plasmodium falciparum malaria worldwide but
      decreased artemisinin susceptibility, phenotypically characterized as slow
      parasite clearance time (PCT), has now been reported in Southeast Asia. This
      makes it all too important to measure the dynamics of parasite clearance in
      African patients treated with ACT over time, to understand trends and detect
      changes early enough to intervene METHODS: Individual patient data from 27
      clinical trials of artesunate-amodiaquine (ASAQ) vs comparators conducted between
      1999 and 2009 were analysed for parasite clearance on modified intent-to-treat
      (ITT) basis. RESULTS: Overall 15,017 patients treated for uncomplicated P.
      falciparum malaria at 44 sites in 20 sub-Saharan African countries were included
      in the analysis; 51% (n=7,660) vs 49% (n=7,357) were treated with ASAQ and
      comparator treatments, respectively. Seventy-seven per cent (77%) were children
      under six years of age. The proportion of the patients treated with ASAQ with
      persistent parasitaemia on Day 2 was 8.6%, and 1.5% on Day 3. Risk factor for not
      clearing parasites on Day 2 and Day 3 calculated by multivariate logistic
      regression with random effect on site and controlling for treatment were: high
      parasitaemia before treatment was (adjusted risk ratios (AOR) 2.12, 95% CI 1.91
      2.35, AOR 2.43, 95% CI 1.98-3.00, respectively); non-ACT treatment (p=0.001, for
      all comparisons). Anaemia (p=0.001) was an additional factor for Day 2 and young
      age (p=0.005) for Day 3.In patients treated with ASAQ in studies who had complete
      parasitaemia data every 24 hours up to Day 3 and additionally Day 7, the parasite
      reduction ratio was 93.9% by Day 1 and 99.9% by Day 2. Using the median
      parasitaemia before treatment (p0=27,125 MUL) and a fitted model, the predicted
      PCT (pPCT = 3.614*ln (p0) - 6.135, r(2) = 0.94) in ASAQ recipients was 31 hours.
      CONCLUSION: Within the period covered by these studies, rapid Plasmodium
      falciparum clearance continues to be achieved in Sub-Saharan African patients
      treated with ACT, and in particular with ASAQ. The prediction formula for
      parasite clearance time could be a pragmatic tool for studies with binary
      outcomes and once-daily sampling, both for research and monitoring purposes.

PMID- 24666564
TI  - L-type Ca(2+) channel current characteristics are preserved in rat tail artery
      myocytes after one-day storage.
AB  - AIM: To develop a cheap and simple method of storing for 24-h vascular tissue and
      single myocytes while preserving therein the biophysical and pharmacological
      characteristics of L-type Ca(2+) channels and contractile activity. METHODS:
      Rings or vascular smooth muscle cells obtained from the rat tail main artery were
      used either freshly (R0h and VSMC0h) or stored for 24 h (R24h and VSMC24h) at 4 
      degrees C, to record whole-cell L-type Ca(2+) currents (IC a(L) ) or measure
      contractile responses. RESULTS: R0h/VSMC0h and R24h/VSMC24h comparably contracted
      when stimulated with phenylephrine, high KCl or ATP. In both VSMC0h and VSMC24h,
      IC a(L) was identified and characterized as a stable inward current for at least
      35 min; IC a(L) was comparably inhibited by the Ca(2+) antagonists nifedipine,
      verapamil and diltiazem and increased by the Ca(2+) channel agonist (S)-(-)-Bay K
      8644; current density and current-voltage relationships were similar; at more
      hyperpolarized holding potentials, IC a(L) intensity increased comparably;
      nifedipine shifted the steady-state inactivation curve towards more negative
      potentials, while verapamil blocked IC a(L) in a frequency-dependent manner and
      slowed down the rate of recovery from inactivation in a comparable way.
      CONCLUSION: Findings show that smooth muscle contractile activity and the
      biophysical and pharmacological features of L-type Ca(2+) channels are similar in
      VSMC24h and VSMC0h. The fact that reproducible results were obtained in vascular
      myocytes up to 24 h after dissociation may facilitate vascular smooth muscle cell
      investigation by increasing throughput and reducing the number of animals
      required.

PMID- 24666566
TI  - Review of the prevalence of diabetic retinopathy in Indigenous Australians.
AB  - The purpose of this review is to compare the prevalence of diabetic retinopathy
      (DR) between Indigenous and non-Indigenous Australians with Diabetes Mellitus
      (DM). Australian DR prevalence data from 6 Indigenous studies (n = 2865) and 5
      non-Indigenous studies (n = 9801) conducted between 1985 and 2013 were included
      for analysis. Estimated prevalence of any DR among Indigenous Australians with DM
      was 23.4% compared with 28.9% for non-Indigenous Australians (chi(2)  = 26.9, P <
      0.001). In studies performed after 1990, a significantly higher rate of diabetic
      macular edema was found in Indigenous compared with non-Indigenous Australians
      with DM (7.6% versus 4.9%, chi(2)  = 6.67, P = 0.01). Although there are
      limitations in comparing these studies, one explanation for the observed data
      could be a model in which Indigenous Australians are relatively resistant to
      early stage DR, but with a subset progressing to sight threatening DR due to
      individual genetic and environmental susceptibility factors coupled with poor
      glycemic control. 

PMID- 24666565
TI  - 25-hydroxy vitamin D levels are associated with childhood asthma in a population
      based study in Peru.
AB  - BACKGROUND: Vitamin D deficiency may be associated with an increased risk of
      asthma. OBJECTIVE: We studied the association between 25-hydroxy (25-OH) vitamin
      D deficiency and asthma prevalence in two Peruvian populations close to the
      equator but with disparate degrees of urbanization. METHODS: We conducted a
      population-based study in 1441 children in two communities in Peru, of which 1134
      (79%) provided a blood sample for 25-OH vitamin D analysis. RESULTS: In these
      1134 children, mean age was 14.8 years; 52% were boys; asthma and atopy
      prevalence was 12% in Lima vs. 3% in Tumbes (P < 0.001) and 59% in Lima vs. 41%
      in Tumbes (P < 0.001), respectively; and, mean 25-OH vitamin D level was 20.8
      ng/mL in Lima vs. 30.1 ng/mL in Tumbes (P < 0.001). Prevalence of 25-OH vitamin D
      deficiency (< 20 ng/mL) was 47% in Lima vs. 7% in Tumbes (P < 0.001). In multi
      variable logistic regression, we found that lower 25-OH vitamin D levels were
      associated with an increased odds of asthma (OR = 1.7 per each 10 ng/mL decrease
      in 25-OH vitamin D levels, 95% CI 1.2-2.6; P < 0.01). In stratified analyses, the
      association between lower 25-OH vitamin D levels and asthma was limited to
      children with atopy (OR = 2.2, 95% CI 1.3-3.6) and not in those without atopy (OR
      = 0.9, 95% CI 0.5-2.0). We did not find associations between 25-OH vitamin D
      levels and other clinical biomarkers for asthma, including exhaled nitric oxide,
      total serum IgE and pulmonary function. CONCLUSION AND CLINICAL RELEVANCE: Both
      asthma and 25-OH vitamin D deficiency were common among children living in Lima
      (latitude = 12.0  degrees S) but not among those in Tumbes (3.6  degrees S). The
      relationship between 25-OH vitamin D deficiency and asthma was similar in both
      sites and was limited among children with atopy. Future supplementation trials
      may need to consider stratification by atopy at the time of design.

PMID- 24666567
TI  - Rational use of antibiotics for the management of children's respiratory tract
      infections in the ambulatory setting: an evidence-based consensus by the Italian
      Society of Preventive and Social Pediatrics.
AB  - BACKGROUND: Several guidelines for the management of respiratory tract infections
      in children are available in Italy, as well as in other European countries and
      the United States of America. However, poor adherence to guidelines and the
      sustained inappropriate use of antibiotics have been reported. In the outpatient
      setting, almost half of antibiotics are prescribed for the treatment of common
      respiratory tract infections. In Italy the antibiotic prescription rate is
      significantly higher than in other European countries, such as Denmark or the
      Netherlands, and also the levels of antibiotic resistance for a large variety of
      bacteria are higher. Therefore, the Italian Society of Preventive and Social
      Paediatrics organised a consensus conference for the treatment of respiratory
      tract infections in children to produce a brief, easily readable, evidence-based
      document. METHODS: The conference method was used, according to the National
      Institute of Health and the National Plan Guidelines. A literature search was
      performed focusing on the current guidelines for the treatment of airway
      infections in children aged 1 month-18 years in the ambulatory setting. RESULTS:
      Recommendations for the treatment of acute pharyngitis, acute otitis media,
      sinusitis, and pneumonia have been summarized. Conditions for which antibiotic
      treatment should not be routinely prescribed have been highlighted. CONCLUSION:
      This evidence-based document is intended to accessible to primary care
      pediatricians and general practice physicians in order to make clinical practice
      uniform, in accordance with the recommendations of the current guidelines.

PMID- 24666568
TI  - Multimodal treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) represents the most common liver cancer with an
      increasing incidence and it accounts for the third most common cause of cancer
      related death worldwide. Even though the clinical diagnosis and management of HCC
      improved significantly in the last decades, this malignant disease is still
      associated with a poor prognosis. It has to be distinguished between patients
      with HCCs, which developed from liver cirrhosis, and patients without underlying
      liver cirrhosis as classification systems, prognosis estimation and therapy
      recommendations differ in-between. In case of HCC in patients with liver
      cirrhosis in Europe, treatment allocation and prognosis estimation are mainly
      based on the Barcelona-Clinic Liver Cancer (BCLC) staging system. Based on this
      staging system different surgical, interventional radiological/sonographical and
      non-interventional procedures have been established for the multimodal treatment
      of HCC. The BCLC classification system represents a decision guidance; however
      because of its limitations in selected patients treatment allocation should be
      determined on an individualized rather than a guideline-based medicine by a
      multidisciplinary board in order to offer the best treatment option for each
      patient. This review summarizes the current management of HCC and illustrates
      controversial areas of therapeutic strategies.

PMID- 24666570
TI  - [Health services supply and the economic crisis: either we fund goods and
      services according to their value or we become bankrupt. SESPAS report 2014].
AB  - Health policy has reacted to the financial crisis by overemphasising measures
      targeted at reducing unit costs, increasing barriers to access (waiting lists) or
      closing premises. It is too soon for scientific assessment of the impact of this
      reshaping of supply on equity, quality and safety, and on individual and
      population health. Nevertheless, the emergency measures taken to achieve fiscal
      stabilization have shifted the focus to resolving budget problems at the expenses
      of sounder and deeper initiatives aimed at deciding what must be funded and how.
      This article advocates a policy based on selective funding of services and
      benefits on the basis of their value. Other countries' experiences can serve as a
      useful guide, including robust methods to identify technologies (or their uses)
      of questionable value, prioritization criteria, and careful consideration of
      limitations associated with the elimination of a certain benefit, especially if
      it affects the founding values of the system. The necessary tools are available
      to the Spanish health system: the regulatory framework and technical bodies able
      to identify lower value care, support for decision-making, and timely evaluation
      of such decisions. Despite the numerous hurdles, maintaining the status quo is
      too expensive a choice, given the opportunity costs of effectiveness and safety
      losses, measured in terms of equity and the economic efficiency of the Spanish
      health system, which may ultimately translate into worsening of the population's
      health status. 

PMID- 24666569
TI  - [Trends in socioeconomic inequalities in general mortality in the city of Cadiz,
      Spain (1992-2007)].
AB  - OBJECTIVE: To analyze trends in socioeconomic inequality in mortality in the city
      of Cadiz (Spain) from 1992 to 2007. METHODS: An ecological study was performed of
      trends over 3 cross-sections, with the census tract as the unit of analysis.
      Deaths were grouped into three periods: 1992-1996, 1997-2001 and 2002-2007 and
      were then classified according to a deprivation index of the census tract. We
      calculated adjusted rates by the direct method and three measures of health
      inequality. RESULTS: Of 18,586 deaths, 96.7% was geocoded to a census tract. The
      population-attributable risk decreased in men and women, respectively, from 15.4%
      and 12.2% in 1992-1996 to 9.3% and 5.6% in 2002-2007. The other measures, slope
      index and the relative index also showed a decline in inequality but only among
      women. CONCLUSIONS: Despite a decreasing trend, social inequalities are a
      substantial component in the distribution of overall mortality in the city of
      Cadiz.

PMID- 24666571
TI  - Selection for sex in finite populations.
AB  - Finite population size generates interference between selected loci, which has
      been shown to favour increased rates of recombination. In this article, I present
      different analytical models exploring selection acting on a 'sex modifier locus'
      (that affects the relative investment into asexual and sexual reproduction) in a
      finite population. Two forms of selective forces act on the modifier: direct
      selection due to intrinsic costs associated with sexual reproduction and indirect
      selection generated by one or two other loci affecting fitness. The results show
      that indirect selective forces differ from those acting on a recombination
      modifier even in the case of a haploid population: in particular, a single
      selected locus generates indirect selection for sex, while two loci are required
      in the case of a recombination modifier. This effect stems from the fact that
      modifier alleles increasing sex escape more easily from low-fitness genetic
      backgrounds than alleles coding for lower rates of sex. Extrapolating the results
      from three-locus models to a large number of loci at mutation-selection balance
      indicates that in the parameter range where indirect selection is strong enough
      to outweigh a substantial cost of sex, interactions between selected loci have a
      stronger effect than the sum of individual effects of each selected locus.
      Comparisons with multilocus simulation results show that such extrapolations may
      provide correct predictions for the evolutionarily stable rate of sex, unless the
      cost of sex is high. 

PMID- 24666572
TI  - Removal of partial volume averaging with free water in MR diffusion tensor
      imaging using inversion recovery for b0 image.
AB  - PURPOSE: To remove the partial volume averaging effect of free water in MR
      diffusion imaging of neural tissues by use of the fluid attenuated inversion
      recovery (FLAIR) without the penalty of an extended scan time. MATERIALS AND
      METHODS: The magnetic resonance images were obtained from a normal volunteer in a
      coronal slice orientation at 3T with the 20-channel rf coil. In diffusion imaging
      only the b0 images were obtained with the FLAIR contrast while the diffusion
      weighted images were obtained without the FLAIR contrast. A composition of FLAIR
      b0 and non-FLAIR diffusion weighted images was used in calculating the diffusion
      tensor and fractional anisotropy after compensating the reduced signal amplitude
      due to the inversion recovery in the FLAIR b0 images. The fractional anisotropy
      of the non-FLAIR, FLAIR, and the composite methods were analyzed for the mean and
      histogram in the corpus callosum, cervical spine, and the fornix tracts. RESULTS:
      The partial volume averaging effect was observed in the corpus callosum, the
      cervical spine, and the fornix tracts in the non-FLAIR b0 and diffusion images.
      The partial volume averaging effect was removed in the FLAIR diffusion images
      which took more than twice the scan time than the non-FLAIR diffusion imaging.
      The proposed composite FLAIR diffusion imaging removed the partial volume
      averaging effect as in the FLAIR diffusion imaging. The distribution of the FA
      histogram was very different between the non-FLAIR and FLAIR diffusion images,
      while it was very similar between the FLAIR and the composite FLAIR after
      correcting the white matter signal in the FLAIR b0 images. CONCLUSIONS: The
      proposed composite FLAIR diffusion imaging method was equally effective in
      removing the partial volume averaging effect as the FLAIR diffusion imaging at a
      limited increase of the scan time since only a small number of b0 images needed
      to be obtained with the FLAIR contrast.

PMID- 24666573
TI  - Improving detection specificity of iron oxide nanoparticles (IONPs) using the
      SWIFT sequence with long T(2) suppression.
AB  - In order to improve the detection specificity of iron oxide nanoparticles (IONPs)
      delivered to tumors, we embedded saturation pulses into the sweep imaging using
      Fourier transformation (SWIFT) sequence to suppress long T(2) tissues and fat.
      Simulation of the Bloch equation was first conducted to study behavior of the
      saturation pulses of various lengths under different T(2) and off-resonance
      conditions. MR experiments were then conducted using in vivo mouse xenografts and
      a phantom consisting of IONPs, vegetable oil, and explanted tumor specimen,
      without and with long T(2) suppression under a 7T magnetic field. For the in vivo
      study, arginine-glycine-aspartate (RGD) coated 10nm IONPs (RGD-IONPs) were
      delivered to tumors implanted in nude mice through both intra-tumor and
      intravenous injections. Histological studies confirmed that RGD-IONPs efficiently
      homed to tumors through RGD-integrin interaction. Compared to conventional SWIFT,
      the proposed method resulted in sufficient suppression on long T(2) species but
      less influence on short T(2) species. For both the in vivo and ex vivo studies,
      significantly improved contrast-to-noise ratio (CNR) was achieved between the
      IONPs and the long T(2) species.

PMID- 24666574
TI  - Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MR finding
      of radiation-induced hepatic injury: relationship to absorbed dose and time
      course after irradiation.
AB  - PURPOSE: To evaluate if Gd-EOB-DTPA-enhanced MRI could identify liver tissue
      damage caused by radiation exposure in patients undergoing external beam
      radiation therapy. MATERIALS AND METHODS: We enrolled 11 patients who underwent
      Gd-EOB-DTPA-enhanced MRI during or after radiotherapy in which the radiation
      field included the liver. External beam radiotherapy was delivered through
      multiple fields using a 10-MV linear accelerator. The hepatobiliary phase images
      of Gd-EOB-DTPA-enhanced MRI were qualitatively evaluated for the presence of a
      decreased uptake of Gd-EOB-DTPA in the irradiated area in the liver. Next, signal
      intensity (SI) ratio of the irradiated area to the non-irradiated liver
      parenchyma was also calculated. The absorbed dose of the irradiated area in the
      liver was standardized using equivalent dose in 2Gy fraction (EQD2) and
      biological effective dose (BED). The results of qualitative analysis were
      compared with EQD2 or BED, and linear regression analysis was performed between
      EQD2 or BED and SI ratio. RESULTS: Twenty-two irradiated areas were evaluated.
      Qualitative analysis revealed a decreased uptake of Gd-EOB-DTPA in 14 areas and
      no decreased uptake of Gd-EOB-DTPA in eight areas. The thresholds of EQD2 and BED
      causing a decreased uptake of Gd-EOB-DTPA were considered to be 24 to 29Gy and 29
      to 35Gy, respectively. Quantitatively, SI ratio decreased as EQD2 or BED
      increased (r=0.89, p<0.001), and the inverse relationship between signal
      enhancement and the absorbed dose in the irradiated area was obtained. One area
      with EQD2 of 50Gy and BED of 60Gy showed a slightly decreased uptake of Gd-EOB
      DTPA on the 40th day but a clearly decreased uptake of Gd-EOB-DTPA on the 123rd
      day from initiation of radiotherapy. CONCLUSIONS: Gd-EOB-DTPA-enhanced MRI
      described RLI as a decreased uptake of Gd-EOB-DTPA matching the irradiated area.
      The occurrence of this finding was significantly correlated with the absorbed
      dose of the irradiated area in the liver.

PMID- 24666575
TI  - Questions in response to "improved survival after adding dissection of the
      superior mesenteric vein lymph node in advanced distal gastric cancer".

PMID- 24666576
TI  - Reply to: appropriate statistical descriptions for evaluating the predictive role
      of epithelial-to-mesenchymal transition in patients with pancreatic cancer.

PMID- 24666577
TI  - Why was there no mention of informed consent and ethics committee approval in a
      prospective trial?

PMID- 24666578
TI  - Dermatomyositis-like eruption associated with hydroxyurea therapy: a premalignant
      condition?

PMID- 24666579
TI  - Measuring the health systems impact of disease control programmes: a critical
      reflection on the WHO building blocks framework.
AB  - BACKGROUND: The WHO health systems Building Blocks framework has become
      ubiquitous in health systems research. However, it was not developed as a
      research instrument, but rather to facilitate investments of resources in health
      systems. In this paper, we reflect on the advantages and limitations of using the
      framework in applied research, as experienced in three empirical vaccine studies
      we have undertaken. DISCUSSION: We argue that while the Building Blocks framework
      is valuable because of its simplicity and ability to provide a common language
      for researchers, it is not suitable for analysing dynamic, complex and inter
      linked systems impacts. In our three studies, we found that the mechanical
      segmentation of effects by the WHO building blocks, without recognition of their
      interactions, hindered the understanding of impacts on systems as a whole. Other
      important limitations were the artificial equal weight given to each building
      block and the challenge in capturing longer term effects and opportunity costs.
      Another criticism is not of the framework per se, but rather how it is typically
      used, with a focus on the six building blocks to the neglect of the dynamic
      process and outcome aspects of health systems.We believe the framework would be
      improved by making three amendments: integrating the missing "demand" component;
      incorporating an overarching, holistic health systems viewpoint and including
      scope for interactions between components. If researchers choose to use the
      Building Blocks framework, we recommend that it be adapted to the specific study
      question and context, with formative research and piloting conducted in order to
      inform this adaptation. SUMMARY: As with frameworks in general, the WHO Building
      Blocks framework is valuable because it creates a common language and shared
      understanding. However, for applied research, it falls short of what is needed to
      holistically evaluate the impact of specific interventions on health systems. We
      propose that if researchers use the framework, it should be adapted and made
      context-specific.

PMID- 24666580
TI  - Cooling of pirapitinga (Piaractus brachypomus) embryos stored at -10oC.
AB  - Cryopreservation has not been used successfully to preserve fish embryos,
      although chilling techniques have been used with good results. The aim of this
      study was to chill Piaractus brachypomus embryos at - 10 degrees C for various
      storage times. Embryos at the following ontogenetic stages were used: blastoderm 
      1.2 hours post-fertilization (hpf); epiboly - 5 hpf; blastopore closure - 8 hpf;
      and appearance of the optic vesicle - 13 hpf. One hundred embryos were selected
      from each ontogenetic stage and chilled at - 10 degrees C for 6 or 10 h. The
      results were analysed using analysis of variance (ANOVA) and Tukey's test at a 5%
      significance level. A significantly greater number of completely developed live
      larvae were observed following embryonic treatment with a cryoprotectant solution
      that contained 17.5% sucrose and 10% methanol. There was no survival for embryos
      cooled at - 10 degrees C in initial developmental stages (1, 2 and 5 h hpf).
      Furthermore, higher survival rates were observed when embryos were treated at
      more advanced developmental stages (8 and 13 hpf). Therefore, P. brachypomus
      embryos at the blastopore-closure (8 hpf) or appearance-of-optic-vesicle (13 hpf)
      stages should be used for embryo chilling protocols and chilling should be
      performed using a 17.5% sucrose with a 10% methanol solution at - 10 degrees C
      for up to 6 h. The best results were obtained with 13-hpf and 8-hpf embryos and
      cooling at 6 h of storage. 

PMID- 24666581
TI  - GLP-1-mediated gene therapy approaches for diabetes treatment.
AB  - Glucagon-like peptide (GLP)-1 is an incretin hormone with several antidiabetic
      functions including stimulation of glucose-dependent insulin secretion, increase
      in insulin gene expression and beta-cell survival. Despite the initial technical
      difficulties and profound inefficiency of direct gene transfer into the pancreas
      that seriously restricted in vivo gene transfer experiments with GLP-1, recent
      exploitation of various routes of gene delivery and alternative means of gene
      transfer has permitted the detailed assessment of the therapeutic efficacy of GLP
      1 in animal models of type 2 diabetes (T2DM). As a result, many clinical benefits
      of GLP-1 peptide/analogues observed in clinical trials involving induction of
      glucose tolerance, reduction of hyperglycaemia, suppression of appetite and food
      intake linked to weight loss have been replicated in animal models using gene
      therapy. Furthermore, GLP-1-centered gene therapy not only improved insulin
      sensitivity, but also reduced abdominal and/or hepatic fat associated with
      obesity-induced T2DM with drastic alterations in adipokine profiles in treated
      subjects. Thus, a comprehensive assessment of recent GLP-1-mediated gene therapy
      approaches with detailed analysis of current hurdles and resolutions, is
      discussed. 

PMID- 24666582
TI  - Efficacy and safety of bevacizumab in elderly patients with metastatic colorectal
      cancer: results from the Czech population-based registry.
AB  - BACKGROUND: Patients aged 65 years and older represent the majority of patients
      with metastatic colorectal cancer (mCRC). However, this patient population is
      often underrepresented in clinical trials and probably undertreated in the
      clinical practice. METHODS: We have analysed the outcomes of 3,187 mCRC patients
      treated with first-line bevacizumab based on data from the Czech national
      registry of mCRC patients aiming to compare the treatment efficacy and safety
      according to the age categories. RESULTS: In total, 2,126 (66.7%), 932 (29.2%),
      and 129 (4.0%) patients were aged <65 years, 65 to 75 years, and 75+ years,
      respectively. Median progression-free survival (PFS) was 11.4, 11.3, and 11.8
      months for patients aged <65 years, 65 to 75 years, and 75+ years, respectively
      (p = 0.94). Median overall survival (OS) was 26.9, 27.5, and 25.1 months for
      patients aged <65 years, 65 to 75 years, and 75+ years, respectively (p = 0.73).
      Using multivariable Cox model for both PFS and OS, the patient age was not
      significantly associated with either PFS or OS. No increase in bevacizumab
      related toxicity was observed among the elderly mCRC patients with the exception
      of hypertension, which was observed in 71 (3.3%), 34 (3.6%), and 10 (7.8%)
      patients aged <65 years, 65 to 75 years, and 75+ years, respectively.
      CONCLUSIONS: The results of the present study suggest similar outcome in terms of
      OS and PFS with bevacizumab-containing therapy in elderly mCRC patients fit for
      chemotherapy combined with targeted therapy compared to younger patients. Thus,
      chronological age should not be considered to represent a limitation in
      prescribing bevacizumab-containing therapy in mCRC patients.

PMID- 24666583
TI  - Successful treatment of spontaneous intracranial hypotension due to prominent
      cervical cerebrospinal fluid leak with cervical epidural blood patch.
AB  - OBJECTIVE: To report a case of successful treatment of a patient with spontaneous
      intracranial hypotension correlated with MRI finding of cerebrospinal fluid (CSF)
      leak with extradural collection at the upper cervical spinal level. DESIGN: Case
      report. SETTING: An academic tertiary pain management center. METHODS:
      Fluoroscopically guided placement of an 18-gauge epidural needle into epidural
      space at the C7-T1 level was performed; an epidural catheter (Braun Perifix 20G)
      was advanced to C2 level (first patch) and C3 level (second patch). An
      epidurogram with Omnipaque injections confirmed contrast in the posterior and
      lateral epidural space. Autologous venous blood was then administered through the
      catheter. RESULTS: This patient received two lumbar epidural blood patches
      without lasting relief. Given the radiographic evidence of prominent CSF leak
      with extradural fluid collection at C1-2 level, the patient was then treated with
      a cervical epidural blood patch, which provided headache pain relief lasting 6
      months. A second cervical epidural blood patch was performed, and the patient has
      been headache-free for nearly one year to date. CONCLUSION: Based on the
      successful treatment of this patient's spontaneous intracranial hypotension, we
      advocate that patients undergo epidural blood patches to target the site of any
      CSF leak identified by imaging studies to improve the efficacy of this
      intervention. This case demonstrates that cervical epidural blood patch, despite
      its inherent risks, may be more effective than lumbar epidural blood patch in
      treatment of cervical CSF leak.

PMID- 24666584
TI  - A data repository and analysis framework for spontaneous neural activity
      recordings in developing retina.
AB  - BACKGROUND: During early development, neural circuits fire spontaneously,
      generating activity episodes with complex spatiotemporal patterns. Recordings of
      spontaneous activity have been made in many parts of the nervous system over the
      last 25 years, reporting developmental changes in activity patterns and the
      effects of various genetic perturbations. RESULTS: We present a curated
      repository of multielectrode array recordings of spontaneous activity in
      developing mouse and ferret retina. The data have been annotated with minimal
      metadata and converted into HDF5. This paper describes the structure of the data,
      along with examples of reproducible research using these data files. We also
      demonstrate how these data can be analysed in the CARMEN workflow system. This
      article is written as a literate programming document; all programs and data
      described here are freely available. CONCLUSIONS: 1. We hope this repository will
      lead to novel analysis of spontaneous activity recorded in different
      laboratories. 2. We encourage published data to be added to the repository. 3.
      This repository serves as an example of how multielectrode array recordings can
      be stored for long-term reuse.

PMID- 24666585
TI  - Fructose in obesity and cognitive decline: is it the fructose or the excess
      energy?
AB  - We read with interest the review by Lakhan and Kirchgessner, proposing that high
      fructose intake promotes obesity, metabolic syndrome, diabetes, and cognitive
      decline. Their focus on the role of fructose seems premature due to confounding
      from energy and the heavy reliance on low quality evidence from animal models.
      There is a lack of high quality evidence directly assessing the role of fructose
      in cognitive decline. Although one cannot exclude the possibility of a link, it
      remains an unconfirmed hypothesis. 

PMID- 24666586
TI  - The relationship between South Korean clinical nurses' attitudes toward
      organizations and voluntary turnover intention: A path analysis.
AB  - The purpose of this study was to examine the relationship between attitudes
      toward their organizations and voluntary turnover intention among South Korean
      clinical nurses. Data from a total of 312 clinical nurses in six hospitals in
      South Korea were collected for the study. Both hierarchical multiple regression
      analysis and path analysis were used to analyse the data. The overall fit of the
      hypothetical model was good. Voluntary turnover intention was found to have
      significant direct pathways to job embeddedness and organizational commitment.
      Organizational commitment and satisfaction with organizational rewards had
      indirect pathways to voluntary turnover intention through job embeddedness. All
      variances explained 62.3% of the voluntary turnover intention scores. The
      findings suggest that greater job embeddedness, organizational commitment and
      satisfaction with organizational rewards lead to lower voluntary turnover
      intention among clinical nurses in South Korea. 

PMID- 24666589
TI  - How fresh a look? A reply to Heyes.

PMID- 24666587
TI  - Bioinformatics analysis of transcriptional regulation of circadian genes in rat
      liver.
AB  - BACKGROUND: The circadian clock is a critical regulator of biological functions
      controlling behavioral, physiological and biochemical processes. Because the
      liver is the primary regulator of metabolites within the mammalian body and the
      disruption of circadian rhythms in liver is associated with severe illness,
      circadian regulators would play a strong role in maintaining liver function.
      However, the regulatory structure that governs circadian dynamics within the
      liver at a transcriptional level remains unknown. To explore this aspect, we
      analyzed hepatic transcriptional dynamics in Sprague-Dawley rats over a period of
      24 hours to assess the genome-wide responses. RESULTS: Using an unsupervised
      consensus clustering method, we identified four major gene expression clusters,
      corresponding to central carbon and nitrogen metabolism, membrane integrity,
      immune function, and DNA repair, all of which have dynamics which suggest
      regulation in a circadian manner. With the assumption that transcription factors
      (TFs) that are differentially expressed and contain CLOCK:BMAL1 binding sites on
      their proximal promoters are likely to be clock-controlled TFs, we were able to
      use promoter analysis to putatively identify additional clock-controlled TFs
      besides PARF and RORA families. These TFs are both functionally and temporally
      related to the clusters they regulate. Furthermore, we also identified
      significant sets of clock TFs that are potentially transcriptional regulators of
      gene clusters. CONCLUSIONS: All together, we were able to propose a regulatory
      structure for circadian regulation which represents alternative paths for
      circadian control of different functions within the liver. Our prediction has
      been affirmed by functional and temporal analyses which are able to extend for
      similar studies.

PMID- 24666590
TI  - Chronic glucocorticoid treatment increases de novo lipogenesis in visceral
      adipose tissue.

PMID- 24666588
TI  - The regulatory T cells induction by epicutaneous immunotherapy is sustained and
      mediates long-term protection from eosinophilic disorders in peanut-sensitized
      mice.
AB  - BACKGROUND: Allergen-specific immunotherapy favours immune deviation from a Th2
      to a Th1 response and increases the number of regulatory T cells (Tregs).
      Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and
      the allergen-specific Th2 responses and increases local and peripheral Foxp3(+)
      Tregs. OBJECTIVE: To investigate the role of Tregs in EPIT and characterize their
      phenotype and maintenance following EPIT. METHODS: Tregs were investigated using
      in vivo depletion or adoptive transfer into BALB/c mice. Tregs were depleted
      using anti-CD25 antibody injection during EPIT, and allergen-specific responses
      were compared with Sham, EPIT alone and naive mice. To demonstrate that Tregs can
      mediate protection by their own, and to study their maintenance following the end
      of EPIT, CD25(+) CD4(+) Tregs isolated from mice just after or 8 weeks after EPIT
      were transferred into peanut-sensitized mice. Foxp3-IRES-mRFP mice were
      transferred with EPIT-induced Tregs to analyse the induction of host Tregs.
      RESULTS: The anti-CD25 antibody injection to EPIT mice abrogated the induction of
      Tregs in spleen and the expression of Foxp3 in oesophagus. This resulted in
      levels of peanut-induced eosinophilic infiltration in oesophagus similar to Sham
      and significantly higher than EPIT. Whereas the transfer of Tregs from Sham
      treated mice demonstrated no effect, the transfer of Tregs isolated just after
      EPIT prevented peanut-induced eosinophil infiltration and eotaxin expression and
      induced Foxp3 in oesophagus. The transfer of Tregs isolated 8 weeks after EPIT
      suppressed allergen-specific responses as efficiently as did Tregs isolated just
      after EPIT and increased spleen Foxp3(+) CD25(+) CD4(+) cells similarly. The use
      of reporter mice demonstrated an increase in host Tregs. CONCLUSIONS: These
      results confirm the Tregs-mediated mechanism of EPIT and demonstrate the
      persistence of efficient Tregs during a long period of time after treatment
      cessation. This suggests that EPIT induces long-term tolerance in peanut
      sensitized mice.

PMID- 24666592
TI  - Recent developments in the field of bending rigidity measurements on membranes.
AB  - This review gives a brief overview of experimental approaches used to assess the
      bending rigidity of membranes. Emphasis is placed on techniques based on the use
      of giant unilamellar vesicles. We summarize the effect on the bending rigidity of
      membranes as a function of membrane composition, presence of various inclusions
      in the bilayer and molecules and ions in the bathing solutions. Examples for the
      impact of temperature, cholesterol, some peptides and proteins, sugars and salts
      are provided and the literature data are discussed critically. Future directions,
      open questions and possible developments in this research field are also
      included. 

PMID- 24666593
TI  - A peptide hormone gene, GhPSK promotes fibre elongation and contributes to longer
      and finer cotton fibre.
AB  - Cotton fibres, the single-celled trichomes derived from the ovule epidermis,
      provide the most important natural material for the global textile industry. A
      number of studies have demonstrated that regulating endogenous hormone levels
      through transgenic approaches can improve cotton fibre qualities. Phytosulfokine
      alpha (PSK-alpha) is a novel peptide hormone in plants that is involved in
      regulating cell proliferation and elongation. However, its potential applications
      in crop genetic improvement have not been evaluated. In this study, we describe
      how exogenous PSK-alpha application promotes cotton fibre cell elongation in
      vitro. Chlorate, an effective inhibitor of peptide sulfation, suppressed fibre
      elongation in ovule culture. Exogenously applied PSK-alpha partly restored the
      chlorate-induced suppression. A putative PSK gene (GhPSK) was cloned from
      Gossypium hirsutum. Expression pattern analysis revealed that GhPSK is
      preferentially expressed in rapidly elongating fibre cells (5-20 days
      postanthesis). Overexpression of GhPSK in cotton increased the endogenous PSK
      alpha level and promoted cotton fibre cell elongation, resulting in longer and
      finer fibres. Further results from electrophysiological and physiological
      analyses suggest that GhPSK affects fibre development through regulation of K(+)
      efflux. Digital gene expression (DGE) profile analysis of GhPSK overexpression
      lines indicates that PSK signalling may regulate the respiratory electron
      transport chain and reactive oxygen species to affect cotton fibre development.
      These results imply that peptide hormones are involved in cotton fibre growth and
      suggest a new strategy for the biotechnological improvement of cotton fibre
      quality. 

PMID- 24666591
TI  - Thrombolysis ImPlementation in Stroke (TIPS): evaluating the effectiveness of a
      strategy to increase the adoption of best evidence practice--protocol for a
      cluster randomised controlled trial in acute stroke care.
AB  - BACKGROUND: Stroke is a leading cause of death and disability internationally.
      One of the three effective interventions in the acute phase of stroke care is
      thrombolytic therapy with tissue plasminogen activator (tPA), if given within 4.5
      hours of onset to appropriate cases of ischaemic stroke. OBJECTIVES: To test the
      effectiveness of a multi-component multidisciplinary collaborative approach
      compared to usual care as a strategy for increasing thrombolysis rates for all
      stroke patients at intervention hospitals, while maintaining accepted benchmarks
      for low rates of intracranial haemorrhage and high rates of functional outcomes
      for both groups at three months. METHODS AND DESIGN: A cluster randomised
      controlled trial of 20 hospitals across 3 Australian states with 2 groups: multi-
      component multidisciplinary collaborative intervention as the experimental group
      and usual care as the control group. The intervention is based on behavioural
      theory and analysis of the steps, roles and barriers relating to rapid assessment
      for thrombolysis eligibility; it involves a comprehensive range of strategies
      addressing individual-level and system-level change at each site. The primary
      outcome is the difference in tPA rates between the two groups post-intervention.
      The secondary outcome is the proportion of tPA treated patients in both groups
      with good functional outcomes (modified Rankin Score (mRS <2) and the proportion
      with intracranial haemorrhage (mRS >=2), compared to international benchmarks.
      DISCUSSION: TIPS will trial a comprehensive, multi-component and
      multidisciplinary collaborative approach to improving thrombolysis rates at
      multiple sites. The trial has the potential to identify methods for optimal care
      which can be implemented for stroke patients during the acute phase. Study
      findings will include barriers and solutions to effective thrombolysis
      implementation and trial outcomes will be published whether significant or not.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12613000939796.

PMID- 24666594
TI  - What does high and low have to do with it? Performance classification to identify
      health system factors associated with effective prevention of mother-to-child
      transmission of HIV delivery in Mozambique.
AB  - INTRODUCTION: Efforts to implement and take to scale highly efficacious, low-cost
      interventions to prevent mother-to-child HIV transmission (pMTCT) have been a
      cornerstone of reproductive health services in sub-Saharan Africa for over a
      decade. Yet efforts to increase access and utilization of these services remain
      far from optimal. This study developed and applied an approach to systematically
      classify pMTCT performance to identify modifiable health system factors
      associated with pMTCT performance which may be replicated in other pMTCT systems.
      METHODS: Facility-level performance measures were collected at 30 sites over a 12
      month period and reviewed for consistency. Five combinations of three indicators
      (1. HIV testing; 2. CD4 testing; 3. antiretroviral prophylaxis and combined
      antiretroviral therapy initiation) were compared including a composite of all
      three, a combination of 1. and 3., and each individually. Approaches were
      visually assessed to describe facility performance, focusing on rank order
      consistency across high, medium and low categories. Modifiable and non-modifiable
      factors were ascertained at each site and ranking process was reviewed to
      estimate association with facility performance through unadjusted Chi-square
      tests and logistic regression. After describing factors associated with high
      versus low performing pMTCT clinics, the effect of inclusion of the 10 middle
      performers was assessed. RESULTS: The indicator most consistently associated with
      the reference composite indicator (HIV testing, antiretroviral prophylaxis and
      combined antiretroviral therapy) was the single measure of antiretroviral
      prophylaxis and combined antiretroviral therapy. Lower performing pMTCT clinics
      ranked consistently low across measurement strategies; high and middle performing
      clinics demonstrated more variability. Association between clinic characteristics
      and high pMTCT performance varied markedly across ranking strategies. Using the
      reference composite indicator, larger catchment area, higher number of
      institutional deliveries, onsite CD4 point-of-care capacity, and higher numbers
      of nurses and doctors were associated with high clinic performance while clinic
      location, NGO support, women's support group, community linkages patient-tracking
      systems and stock-outs were not associated with high performance. CONCLUSIONS:
      Classifying high and low performance provided consistent results across ranking
      measures, though granularity was improved by aggregating middle performers with
      either high or low performers. Human resources, catchment size and utilization
      were positively associated with effective pMTCT service delivery.

PMID- 24666595
TI  - Getting health services to three million people with TB.

PMID- 24666596
TI  - Selenium status affects selenoprotein expression, reproduction, and F1 generation
      locomotor activity in zebrafish (Danio rerio).
AB  - Se is an essential trace element, and is incorporated into selenoproteins which
      play important roles in human health. Mammalian selenoprotein-coding genes are
      often present as paralogues in teleost fish, and it is unclear whether the
      expression patterns or functions of these fish paralogues reflect their mammalian
      orthologues. Using the model species zebrafish (Danio rerio; ZF), we aimed to
      assess how dietary Se affects key parameters in Se metabolism and utilisation
      including glutathione peroxidase (GPX) activity, the mRNA expression of key Se
      dependent proteins (gpx1a, gpx1b, sepp1a and sepp1b), oxidative status,
      reproductive success and F1 generation locomotor activity. From 27 d until 254 d
      post-fertilisation, ZF were fed diets with graded levels of Se ranging from
      deficient ( < 0.10 mg/kg) to toxic (30 mg/kg). The mRNA expression of gpx1a and
      gpx1b and GPX activity responded in a similar manner to changes in Se status. GPX
      activity and mRNA levels were lowest when dietary Se levels (0.3 mg/kg) resulted
      in the maximum growth of ZF, and a proposed bimodal mechanism in response to Se
      status below and above this dietary Se level was identified. The expression of
      the sepp1 paralogues differed, with only sepp1a responding to Se status. High
      dietary Se supplementation (30 mg/kg) decreased reproductive success, while the
      offspring of ZF fed above 0.3 mg Se/kg diet had lower locomotor activity than the
      other groups. Overall, the novel finding of low selenoprotein expression and
      activity coinciding with maximum body growth suggests that even small Se-induced
      variations in redox status may influence cellular growth rates.

PMID- 24666598
TI  - From waste to art--The IWWG Art Gallery.

PMID- 24666599
TI  - Feeding behaviour of artificially reared Romane lambs.
AB  - A consequence of increasing litter size in sheep is that a portion of the lambs
      have to be reared artificially. Detailed information about the pattern of milk
      consumption of artificially reared lambs would help improve their management. The
      purpose of this study is to describe the individual and group feeding behaviour
      of 94 Romane artificially reared lambs from 5 to 28 days of age using an
      electronic automatic lamb feeder. Animals were located in four pens of 8 to 15
      lambs of similar age with one teat per pen. They were fed ad libitum. In our
      experimental situation (group rearing, continuous lightning) on average a lamb
      made 1.4+/-0.7 visits to the teat per meal and 9.5+/-3 meals per day. Mean meal
      duration was 247+/-158 s and the mean daily time spent feeding was 38+/-25 min.
      The mean quantity of milk intake was 176+/-132 ml per meal and 1.68+/-0.8 l per
      day. With age, the number of daily meals and their duration decreased while the
      quantity of milk consumed per meal and per day increased. Females tended to make
      more visits to the teat per meal and perform more meals per day but their milk
      consumption per meal was lower. The feed conversion ratio was 1.36+/-0.2.
      Synchrony in feeding (group meal) was estimated as the percentage of lambs that
      wanted to access the teat within the same short period (relative group meal
      size). On average 65% of lambs in the pen wanted to access the teat within the
      same period, but for 35% of group meals the relative group meal size was >90%.
      There was no consistency in the order in which lambs accessed the teat during a
      group meal. Our evaluation suggested that electronic automatic lamb feeders are
      tools that can provide, on a large scale, data describing the feeding behaviour
      of artificially reared lambs. It is then possible to study factors influencing
      these traits in order to improve the outcome of artificially reared lambs. 

PMID- 24666600
TI  - Genetic causes of transitions from sexual reproduction to asexuality in plants
      and animals.
AB  - The persistence of sexual reproduction in the face of competition from asexual
      invaders is more likely if asexual lineages are produced infrequently or have low
      fitness. The generation rate and success of new asexual lineages will be
      influenced by the proximate mechanisms underlying transitions to asexuality. As
      such, characterization of these mechanisms can help explain the distribution of
      reproductive modes among natural populations. Here, we synthesize the literature
      addressing proximate causes of transitions from sexual to asexual reproduction in
      plants and animals. In cyclical and facultatively asexual taxa, individual
      mutations can cause obligate asexuality. The evolution of asexuality in
      obligately sexual groups is more complex, requiring the simultaneous acquisition
      of two traits generally controlled by different genetic factors: unreduced gamete
      formation and spontaneous development of unfertilized gametes. At least three
      'pre-adaptations' could favour transitions to obligate asexuality in obligate
      sexuals. First, linkage among loci affecting separate key components of
      asexuality facilitates its spread, with evidence for these linkage blocks in
      plants. Second, asexuality should evolve more readily in haplodiploids; support
      for this hypothesis comes from two examples where a single locus causes
      transitions to asexuality. Third, standing genetic variation for the production
      of unreduced gametes could facilitate transitions to asexuality, but whether the
      ability to produce unreduced gametes contributes to the evolution of obligate
      asexuality remains unclear. We close by reviewing the associations between
      asexuality, hybridization and polyploidy, and argue that current data suggest
      that hybridization is more likely to play a causal role in transitions to
      asexuality than polyploidy. 

PMID- 24666601
TI  - Middle Paleolithic and Uluzzian human remains from Fumane Cave, Italy.
AB  - The site of Fumane Cave (western Lessini Mountains, Italy) contains a
      stratigraphic sequence spanning the Middle to early Upper Paleolithic. During
      excavations from 1989 to 2011, four human teeth were unearthed from the
      Mousterian (Fumane 1, 4, 5) and Uluzzian (Fumane 6) levels of the cave. In this
      contribution, we provide the first morphological description and morphometric
      analysis of the dental remains. All of the human remains, except for Fumane 6,
      are deciduous teeth. Based on metric data (crown and cervical outline analysis,
      and lateral enamel thickness) and non-metric dental traits (e.g., mid-trigonid
      crest), Fumane 1 (lower left second deciduous molar) clearly belongs to a
      Neandertal. For Fumane 4 (upper right central deciduous incisor), the taxonomic
      attribution is difficult due to heavy incisal wear. Some morphological features
      observed in Fumane 5 (lower right lateral deciduous incisor), coupled with the
      large size of the tooth, support Neandertal affinity. Fumane 6, a fragment of a
      permanent molar, does not show any morphological features useful for taxonomic
      discrimination. The human teeth from Fumane Cave increase the sample of Italian
      fossil remains, and emphasize the need to develop new methods to extract
      meaningful taxonomic information from deciduous and worn teeth. 

PMID- 24666602
TI  - Evolutionary responses of solitary and social Hymenoptera to predation by
      primates and overwhelmingly powerful vertebrate predators.
AB  - Insects provide an important part of the diet of primates, including hominins.
      Investigations of insectivory in primates has focused primarily on the value of
      insects in the diet, and on the means of obtaining the insects, with little
      attention devoted to the predator-prey relationship itself and less to
      evolutionary aspects of insect defense against predatory vertebrates, including
      primates. Data indicate that, far from being a passive half of the relationship,
      insects in general, and stinging Hymenoptera in particular, are active
      participants that have greatly influenced the relationship. Predators have been a
      strong component of the selection pressure in the evolution of painful and toxic
      bee, wasp, and ant stings and these insects, in turn, have influenced hunting
      behavior and learning in at least higher primates. The special example of honey
      bees and humans is highlighted. Both humans and the bees have benefitted from a
      relationship that represents an unprecedented example of a predator-prey
      interaction evolving recently into facultative mutualism.

PMID- 24666603
TI  - Gluteal muscle composition differentiates fallers from non-fallers in community
      dwelling older adults.
AB  - BACKGROUND: Impaired balance, loss of mobility and falls are major problems
      associated with changes in muscle in older adults. However, the extent to which
      muscle composition and related performance measures for different lower limb
      muscles are associated with falls in older individuals is unclear. This study
      evaluated lower limb muscle attenuation, intramuscular adipose tissue (IMAT)
      infiltration and muscle performance in older fallers and non-fallers. METHODS:
      For this cross-sectional study, fifty-eight community dwelling older individuals
      (>65 years) were classified into fallers (n = 15) or non-fallers (n = 43).
      Computed tomography (CT) was used to determine muscle attenuation and
      intramuscular adipose tissue (IMAT) of multiple thigh and hip muscles. Muscle
      performance was assessed with isokinetic dynamometry. RESULTS: For both groups,
      Rectus Femoris showed the highest muscle attenuation and lowest IMAT
      infiltration, and Gluteus Maximus and Gluteus Medius/Minimus muscles had the
      lowest muscle attenuation and highest IMAT infiltration. Fallers exhibited lower
      muscle attenuation and higher IMAT infiltration than non-faller participants in
      most muscles, where the gluteal muscles were the most affected (p < 0.05).
      Fallers also showed a lower peak hip abduction torque (p < 0.05). There were
      significant associations (r = 0.31 to 0.53) between joint torques and muscle
      composition, with the strongest associations between Gluteus Medius/Minimus and
      hip abduction strength. CONCLUSIONS: While fallers were generally differentiated
      from non-fallers by muscle composition, the most affected muscles were the
      proximal gluteal muscles of the hip joint accompanied by lower hip abduction
      strength, which may contribute to impaired balance function and increased risk
      for falls.

PMID- 24666604
TI  - In vitro development of secondary follicles from pre-pubertal and adult goats
      cultured in two-dimensional or three-dimensional systems.
AB  - The aim of this study was to evaluate the influence of two-dimensional (2D) and
      three-dimensional (3D) alginate culture systems on in vitro development of pre
      antral caprine follicles. In addition, the influence of the reproductive age of
      the ovary donor on the in vitro culture success was investigated. Pre-antral
      follicles from pre-pubertal or adult goats were isolated and cultured directly on
      a plastic surface (2D) or encapsulated in an alginate-based matrix (3D). After 18
      days, the oocytes underwent in vitro maturation (IVM) and in vitro fertilization
      (IVF) to produce embryos. The 3D system showed higher rates of follicle survival,
      lower rates of oocyte extrusion, and a greater number of recovered oocytes for
      IVM and IVF (P < 0.05). Only pre-antral follicles from adult animals produced MII
      oocytes and embryos. The estradiol concentrations increased from day 2 to day 12
      of culture in all groups tested (P < 0.05). Conversely, progesterone
      concentrations were lower in 3D-cultured follicles than in 2D-cultured follicles,
      with differences on days 2 and 6 of culture (P < 0.05). We provide compelling
      evidence that a 2D or 3D alginate in vitro culture system offers a promising
      approach to achieving full in vitro development of caprine pre-antral follicles
      to produce mature oocytes that are capable of fertilization and viable embryos. 

PMID- 24666606
TI  - Transcutaneous magnetic stimulation (TMS) in alleviating post-traumatic
      peripheral neuropathic pain States: a case series.
AB  - BACKGROUND: Peripheral nerve injury can result in the formation of neuroma/nerve
      entrapment, a persistent peripheral neuropathic pain state which is often
      refractory to invasive interventions or medications. Therefore, there is a need
      in the field of pain management to develop innovative noninvasive therapy in
      treating post-traumatic peripheral neuropathic pain states. A new intervention,
      transcutaneous magnetic stimulation (tMS), is derived from the use of
      transcranial magnetic stimulation in which a rapid discharge of electric current
      is converted into dynamic magnetic flux for modulating neuronal functions.
      METHODS: Low-frequency (0.5 Hz) tMS was developed over the site of neuroma/nerve
      entrapment in five patients who have failed both steroid injection and
      conventional pain medications. Four hundred pulses of stimulation were delivered
      per treatment session. Each patient received three to four sessions of treatment
      over a period of 2 months. Pre- and post-intervention spontaneous pain levels
      were assessed with a numerical rating pain scale (NRS). RESULT: Five patients
      with post-traumatic neuroma/nerve entrapment pain received the treatment. Average
      pre and postscores (+/-standard deviation) on the NRS were 5.00 (+/-1.41) and
      0.80 (+/-1.10), respectively, with an average pain reduction of 84 (+/-21.91)% in
      the NRS after three to four treatments within 2 months. This analgesic effect
      appeared to be sustainable with repeated treatment delivered at a 6- to 8-week
      duration. Pretreatment tactile allodynia found in three patients resolved after
      the initial 2-month treatment sessions. CONCLUSION: tMS offers a noninvasive
      treatment option for neuroma-related neuropathic pain conditions. Randomized
      controlled studies are required in further validating the efficacy of this
      treatment modality. Additional studies are also needed to assess the underlying
      electrophysiological mechanisms of the observed analgesic benefit.

PMID- 24666605
TI  - Association between obesity and metabolic co-morbidities among children and
      adolescents in South Korea based on national data.
AB  - BACKGROUND: Childhood obesity has become a serious public health threat worldwide
      due to its many short- and long-term adverse health effects. We assessed the
      association between weight status and metabolic co-morbidities among South Korean
      children using nationally representative data. METHODS: Data from the 2007-2008
      Korea National Health and Nutrition Examination Surveys for 1,526 children aged
      10-19 years were used. Logistic regression models were fit to examine the
      association between weight status [overweight, 85th percentile<=BMI<95th
      percentile; obese, BMI>=95th percentile; and central obesity, waist
      circumference>=90th percentile, based on 2007 Korean National Growth Charts] and
      metabolic outcomes. RESULTS: More obese children had metabolic co-morbidities
      than normal-weight children (P<0.05). Boys had higher means BMI than girls, WC,
      and BP, while girls had higher means of total blood cholesterol and HDL
      cholesterol (P<0.05). Attributable risk of metabolic syndrome was high due to
      overweight and obesity: 91.1% for central obesity and 29.6% for high TG. Obese
      children had increased risk of having high BP (adjusted odds ratio (OR): 1.90;
      95% CI: 1.05-3.45), dyslipidemia (OR: 6.21; 95% CI: 3.59-10.75), high TG (OR:
      6.87; 95% CI: 4.05-11.64), low HDL (OR: 4.46; 95% CI: 2.23-8.89), and >=2 co
      morbidities (OR: 26.97; 95% CI: 14.95-48.65) compared to normal-weight subjects,
      while the associations between weight status and metabolic outcomes were stronger
      in boys. CONCLUSIONS: Obesity was strongly associated with metabolic co
      morbidities in South Korean children.

PMID- 24666607
TI  - Exploring the variation in state-level prescription utilization using a
      triangulation of analytic methods.
AB  - BACKGROUND: Retail prescription fill data have consistently shown wide variation
      in prescription drug utilization across states, with state-level rates ranging
      from 8.5 to 19.3 filled prescriptions per capita per year. Empirical explanations
      for this wide variation have not yet been sought. OBJECTIVES: To examine which
      factors potentially explain the wide variation in prescription drug utilization
      across US states. METHODS: Summary data (proportions, counts, rates, etc) on
      sociodemographics, health, insurance, provider density, health service use, and
      retail prescription drug fills for each of the 50 states and the District of
      Columbia, from 2008 to 2010, were retrieved from multiple national data sources,
      such as the Kaiser Family Foundation's "State Health Facts" Web Portal. Pooled
      cross-sectional linear, negative binomial, and ordered logit multivariable
      regressions were used to model states' prescription utilization as a function of
      the aforementioned possible explanatory variables. Principal components analysis
      also was employed so as to overcome high correlations among some of the
      covariates. RESULTS: Among US states, higher levels of employer-sponsored
      insurance or Medicaid coverage were associated with both higher levels of
      prescription utilization and a higher likelihood of being in upper utilization
      quartiles. A higher density of nurse practitioners was also positively associated
      with both the level of utilization and the likelihood of higher utilization,
      whereas a higher density of active physicians was associated with opposite
      effects. Higher prevalence of physical activity was associated with lower
      utilization levels as well as a lower likelihood of high utilization. State-level
      prevalence of chronic conditions and poor health mattered only for the level of
      prescription utilization. States' sociodemographics were not significantly
      associated with prescription utilization. CONCLUSIONS: This study suggests that
      higher prescription utilization across states was associated with the variations
      in provider types, Medicaid and private insurance coverage, as well as the
      prevalence of chronic diseases. Further investigation of how each of these
      factors may contribute to a particular state's prescription drug utilization
      level is needed.

PMID- 24666608
TI  - Identification of two novel cytolysins from the hydrozoan Olindias sambaquiensis
      (Cnidaria).
AB  - BACKGROUND: Although the hydrozoan Olindias sambaquiensis is the most common
      jellyfish associated with human envenomation in southeastern and southern Brazil,
      information about the composition of its venom is rare. Thus, the present study
      aimed to analyze pharmacological aspects of O. sambaquiensis venom as well as
      clinical manifestations observed in affected patients. Crude protein extracts
      were prepared from the tentacles of animals; peptides and proteins were sequenced
      and submitted to circular dichroism spectroscopy. Creatine kinase, cytotoxicity
      and hemolytic activity were evaluated by specific methods. RESULTS: We identified
      two novel cytolysins denominated oshem 1 and oshem 2 from the tentacles of this
      jellyfish. The cytolysins presented the amino acid sequences
      NEGKAKCGNTAGSKLTFKSADECTKTGQK (oshem 1) and NNSKAKCGDLAGWSKLTFKSADECTKTGQKS
      (oshem 2) with respective molecular masses of 3.013 kDa and 3.375 kDa. Circular
      dichroism revealed that oshem 1 has random coils and small alpha-helix
      conformation as main secondary structure whereas oshem 2 presents mainly random
      coils as its main secondary structure probably due to the presence of W (13) in
      oshem 2. The hemolysis levels induced by oshem 1 and oshem 2 using a peptide
      concentration of 0.2 mg/mL were, respectively, 51.7 +/- 6.5% and 32.9 +/- 8.7% (n
      = 12 and p <= 0.05). Oshem 1 and oshem 2 showed significant myonecrotic activity,
      evaluated by respective CK level measurements of 1890.4 +/- 89 and 1212.5 +/- 103
      (n = 4 and p <= 0.05). In addition, myonecrosis was also evaluated by cell
      survival, which was measured at 72.4 +/- 8.6% and 83.5 +/- 6.7% (n = 12 and p <=
      0.05), respectively. The structural analysis showed that both oshem 1 and oshem 2
      should be classified as a small basic hemolytic peptide. CONCLUSION: The amino
      acid sequences of two peptides were highly similar while the primary amino acid
      sequence analysis revealed W (22th) as the most important mutation. Finally oshem
      1 and oshem 2 are the first cytolytic peptides isolated from the Olindias
      sambaquiensis and should probably represent a novel class of cytolytic peptides.

PMID- 24666609
TI  - Determinants of 1-year changes in disease-specific health status in patients with
      advanced chronic obstructive pulmonary disease: A 1-year observational study.
AB  - We aimed to identify baseline and longitudinal determinants of change in disease
      specific health status in patients with advanced chronic obstructive pulmonary
      disease (COPD). Demographic and clinical characteristics as well as disease
      specific health status (St George's Respiratory Questionnaire, SGRQ) were
      assessed in 105 outpatients with advanced COPD at baseline and at 4, 8 and 12
      months. Eighty-five patients (81.0%) had complete SGRQ data at baseline and 12
      months and were included in analyses. Stepwise multiple regression analysis
      revealed that lower SGRQ total score, higher depression scores and longer time
      needed to complete the Timed Up and Go (TUG) test at baseline, as well as
      increase in time needed to complete the TUG test and increase in dyspnoea during
      the 1-year follow-up period, were predictors of deterioration in disease-specific
      health status. The current study reinforces the stimulation of physical mobility
      and the targeting of dyspnoea as components for treatment programs to optimize
      disease-specific health status in patients with advanced COPD. 

PMID- 24666610
TI  - Changing epidemiology of infections due to extended spectrum beta-lactamase
      producing bacteria.
AB  - BACKGROUND: Community-associated infections caused by extended-spectrum beta
      lactamase (ESBL) producing bacteria are a growing concern. METHODS: Retrospective
      cohort study of clinical infections due to ESBL-producing bacteria requiring
      admission from 2006-2011 at a tertiary care academic medical center in
      Providence, RI. RESULTS: A total of 321 infections due to ESBL-producing bacteria
      occurred during the study period. Fifty-eight cases (18%) were community
      acquired, 170 (53%) were healthcare-associated, and 93 (29%) were hospital
      acquired. The incidence of ESBL infections per 10,000 discharges increased during
      the study period for both healthcare-associated infections, 1.9 per year (95% CI
      1-2.8), and for community-acquired infections, 0.85 per year (95% CI 0.3-1.4) but
      the rate remained unchanged for hospital-acquired infections. For ESBL-producing
      E. coli isolates, resistance to both ciprofloxacin and trimethoprim
      sulfamethoxazole was 95% and 65%, respectively but 94% of isolates were
      susceptible to nitrofurantoin. CONCLUSIONS: Community-acquired and healthcare
      associated infections due to ESBL-producing bacteria are increasing in our
      community, particularly urinary tract infections due to ESBL-producing E. coli.
      Most isolates are resistant to oral antibiotics commonly used to treat urinary
      tract infections. Thus, our findings have important implications for outpatient
      management of such infections.

PMID- 24666611
TI  - openBEB: open biological experiment browser for correlative measurements.
AB  - BACKGROUND: New experimental methods must be developed to study interaction
      networks in systems biology. To reduce biological noise, individual subjects,
      such as single cells, should be analyzed using high throughput approaches. The
      measurement of several correlative physical properties would further improve data
      consistency. Accordingly, a considerable quantity of data must be acquired,
      correlated, catalogued and stored in a database for subsequent analysis. RESULTS:
      We have developed openBEB (open Biological Experiment Browser), a software
      framework for data acquisition, coordination, annotation and synchronization with
      database solutions such as openBIS. OpenBEB consists of two main parts: A core
      program and a plug-in manager. Whereas the data-type independent core of openBEB
      maintains a local container of raw-data and metadata and provides annotation and
      data management tools, all data-specific tasks are performed by plug-ins. The
      open architecture of openBEB enables the fast integration of plug-ins, e.g., for
      data acquisition or visualization. A macro-interpreter allows the automation and
      coordination of the different modules. An update and deployment mechanism keeps
      the core program, the plug-ins and the metadata definition files in sync with a
      central repository. CONCLUSIONS: The versatility, the simple deployment and
      update mechanism, and the scalability in terms of module integration offered by
      openBEB make this software interesting for a large scientific community. OpenBEB
      targets three types of researcher, ideally working closely together: (i)
      Engineers and scientists developing new methods and instruments, e.g., for
      systems-biology, (ii) scientists performing biological experiments, (iii)
      theoreticians and mathematicians analyzing data. The design of openBEB enables
      the rapid development of plug-ins, which will inherently benefit from the "house
      keeping" abilities of the core program. We report the use of openBEB to combine
      live cell microscopy, microfluidic control and visual proteomics. In this
      example, measurements from diverse complementary techniques are combined and
      correlated.

PMID- 24666612
TI  - Effect of simvastatin on castration-resistant prostate cancer cells.
AB  - BACKGROUND: In castration-resistant prostate cancer (CRPC), recent evidence has
      demonstrated the persistence of the intratumoral androgens. The multi-step
      androgen synthesis pathway originates from cholesterol, which can be obtained by
      cells from several major sources including intracellular synthesis through an
      enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). The inhibition of
      this enzyme by the use of statins has been investigated in prostate cancer as a
      possible therapeutic target for blocking the de novo androgen synthesis resulting
      in decreased tumor growth. However, the effectiveness of statins in CRPC has not
      been investigated. METHODS: Castration-resistant C4-2 and androgen-sensitive
      LNCaP cells were treated with Simvastatin for 48 hours. Dose-dependent responses
      to Simvastatin were analyzed using cell proliferation and cytotoxicity assays.
      Cellular growth curve was generated using haemocytometer. HMGCR activity was
      assessed using 14C-acetic acid detected by thin layer chromatography, and the
      protein expression was quantified using western blot analysis. Intracellular
      cholesterol and prostate specific antigen (PSA) levels were quantified using
      enzyme-linked immunosorbent assays (ELISA). RESULTS: Significant decrease in cell
      viability and growth curve observed at 75 MUM of Simvastatin compared to no
      treatment group in the castration-resistant C4-2 cells. HMGCR activity was
      significantly decreased up to 50% and 70% at 50 MUM and 75 MUM of Simvastatin
      respectively compared to the vehicle control in C4-2 cells. Simvastatin did not
      affect the protein expression. 80% decrease in the amount of total intracellular
      cholesterol levels was observed in 75 MUM Simvastatin treatment group compared to
      vehicle control. PSA secretion levels were significantly reduced in the C4-2 cell
      line at 50 MUM and 75 MUM of Simvastatin compared to vehicle control. CONCLUSION:
      The inhibition of HMGCR via Simvastatin lowered the viability of castration
      resistant C4-2 cells. Simvastatin's ability to limit the endogenous supply of
      cholesterol contributes to the effects seen in cell viability.

PMID- 24666613
TI  - Leucocyte telomere length as marker for cardiovascular ageing.

PMID- 24666615
TI  - Rich interpretations of infant behaviour are popular, but are they valid? A reply
      to Scott and Baillargeon.

PMID- 24666614
TI  - Artemisinin derivative artesunate induces radiosensitivity in cervical cancer
      cells in vitro and in vivo.
AB  - OBJECTIVE: Cervical cancer is the third most common type of cancer in women
      worldwide and radiotherapy remains its predominant therapeutic treatment.
      Artesunate (ART), a derivative of artemisinin, has shown radiosensitization
      effect in previous studies. However, such effects of ART have not yet been
      revealed for cervical cancer cells. METHODS: The effect of ART on
      radiosensitivity of human cervical cancer cell lines HeLa and SiHa was assessed
      using the clonogenic assay. Cell cycle progression and apoptosis alterations were
      analyzed by flow cytometry. For in vivo study, HeLa or SiHa cells were inoculated
      into nude mice to establish tumors. Tissues from xenografts were obtained to
      detect the changes of microvessel density, apoptosis and cell cycle distribution.
      Microarray was used to analyze differentially expressed genes. RESULTS: ART
      increased the radiosensitivity of HeLa cells (SER=1.43, P<0.001) but not of SiHa
      cells. Apoptosis and the G2-M phase transition induced by X-ray irradiation (IR)
      were enhanced by ART via increased Cyclin B1 expression in HeLa cells. Tumor
      growth of xenografts from HeLa but not SiHa cells was significantly inhibited by
      irradiation combined with ART (tumor volume reduction of 72.34% in IR+ART group
      vs. 41.22% in IR group in HeLa cells and 48.79% in IR+ART group vs. 44.03% in IR
      alone group in SiHa cells). Compared with the irradiated group, cell apoptosis
      was increased and the G2/M cell cycle arrest was enhanced in the group receiving
      irradiation combined with ART. Furthermore, compared with radiation alone, X-ray
      irradiation plus ART affected the expression of 203 genes that function in
      multiple pathways including RNA transport, the spliceosome, RNA degradation and
      p53 signaling. CONCLUSION: ART potently abrogates the G2 checkpoint control in
      HeLa cells. ART can induce radiosensitivity of HeLa cells in vitro and in vivo.

PMID- 24666616
TI  - Decade-long trends in the magnitude, treatment, and outcomes of patients aged 30
      to 54 years hospitalized with ST-segment elevation and non-ST-segment elevation
      myocardial infarction.
AB  - Although acute myocardial infarction (AMI) occurs primarily in the elderly, this
      disease also affects young adults. Few studies have, however, presented data on
      relatively young patients hospitalized with AMI. The objectives of this
      population-based study were to examine recent trends in the magnitude, clinical
      characteristics, management, and in-hospital and long-term outcomes associated
      with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment
      elevation myocardial infarction (NSTEMI) in patients aged 30 to 54 years. We
      reviewed the medical records of 955 residents of the Worcester (Massachusetts)
      metropolitan area aged 30 to 54 years who were hospitalized for an initial STEMI
      or NSTEMI in 6 biennial periods from 1999 to 2009 at 11 greater Worcester medical
      centers. From 1999 to 2009, the proportion of young adults hospitalized with an
      STEMI decreased from approximately 2/3 to 2/5 of all patients with an initial
      AMI. Patients with STEMI were less likely to have a history of heart failure,
      hypertension, hyperlipidemia, and kidney disease than those with NSTEMI. Both
      groups received similar effective medical therapies during their acute
      hospitalization. In-hospital clinical complications and mortality were low and no
      significant differences in these end points were observed between patients with
      STEMI and NSTEMI or with regard to 1-year postdischarge death rates (1.9% vs
      2.8%). The present results demonstrate recent decreases in the proportion of
      relatively young patients diagnosed with an initial STEMI. Patients with STEMI
      and NSTEMI had similar in-hospital outcomes and long-term survival. Trends in
      these and other important outcomes warrant continued monitoring.

PMID- 24666617
TI  - Impact of dual antiplatelet therapy on outcomes among aspirin-resistant patients
      following coronary artery bypass grafting.
AB  - Coronary artery bypass grafting is pivotal in the contemporary management of
      complex coronary artery disease. Interpatient variability to antiplatelet agents,
      however, harbors the potential to compromise the revascularization benefit by
      increasing the incidence of adverse events. This study was designed to define the
      impact of dual antiplatelet therapy (dAPT) on clinical outcomes among aspirin
      resistant patients who underwent coronary artery surgery. We randomly assigned
      219 aspirin-resistant patients according to multiple electrode aggregometry to
      receive clopidogrel (75 mg) plus aspirin (300 mg) or aspirin-monotherapy (300
      mg). The primary end point was a composite outcome of all-cause death, nonfatal
      myocardial infarction, stroke, or cardiovascular hospitalization assessed at 6
      months postoperatively. The primary end point occurred in 6% of patients assigned
      to dAPT and 10% of patients randomized to aspirin-monotherapy (relative risk
      0.61, 95% confidence interval 0.25 to 1.51, p = 0.33). No significant treatment
      effect was noted in the occurrence of the safety end point. The total incidence
      of bleeding events was 25% and 19% in the dAPT and aspirin-monotherapy groups,
      respectively (relative risk 1.34, 95% confidence interval 0.80 to 2.23, p =
      0.33). In the subgroup analysis, dAPT led to lower rates of adverse events in
      patients with a body mass index >30 kg/m(2) (0% vs 18%, p <0.01) and those <65
      years (0% vs 10%, p = 0.02). In conclusion, the addition of clopidogrel in
      patients found to be aspirin resistant after coronary artery bypass grafting did
      not reduce the incidence of adverse events, nor did it increase the number of
      recorded bleeding events. dAPT did, however, lower the incidence of the primary
      end point in obese patients and those <65 years.

PMID- 24666618
TI  - Effect of change in body weight on incident diabetes mellitus in patients with
      stable coronary artery disease treated with atorvastatin (from the treating to
      new targets study).
AB  - Features of the metabolic syndrome are independent risk factors for new-onset
      diabetes mellitus (NODM) related to statin therapy. Obesity is the predominant
      underlying risk factor for the metabolic syndrome and diabetes mellitus. This
      study investigated whether change in body weight may predict NODM in statin
      treated patients. A total of 7,595 patients without prevalent diabetes mellitus
      at baseline from the Treating to New Targets (TNT) study were included in this
      analysis. They were randomized to atorvastatin 10 or 80 mg/day and monitored for
      a median of 4.9 years. NODM developed in 659 patients (8.1% in the 10-mg group
      and 9.2% in the 80-mg group). There was a significant increase in body weight
      (0.9 kg, p <0.01 in both men and women) over 1 year after randomization. The
      increase in body weight was greater in patients with NODM than those without NODM
      (1.6 vs 0.9 kg, p <0.001). The association of change in body weight with NODM
      risk remained significant after adjusting for confounding factors (hazard ratios
      1.33, 1.42, and 1.88 for quartiles 2, 3, and 4 compared with quartile 1,
      respectively). Similar results were obtained in patients with normal fasting
      glucose level. In conclusion, 1-year change in body weight is predictive of NODM
      in patients who underwent statin therapy from the TNT trial. Our study highlights
      the importance of weight control as a lifestyle measure to prevent statin-related
      NODM.

PMID- 24666619
TI  - Readmission rate after coronary artery bypass grafting versus percutaneous
      coronary intervention for unprotected left main coronary artery narrowing.
AB  - Many studies have reported comparable risk of hard end points between
      percutaneous coronary intervention (PCI) and coronary artery bypass grafting
      (CABG) for unprotected left main coronary artery (ULMCA) stenosis. However, there
      are limited data regarding the morbidity associated with ULMCA revascularization.
      This study sought to compare the cause and risk of readmissions after PCI and
      CABG for ULMCA stenosis. We evaluated the unadjusted and adjusted risk of
      readmissions in 1,352 patients (783 PCI treated and 569 CABG treated) who were
      consecutively enrolled in a multicenter registry of patients with ULMCA stenosis,
      named the Premier of Randomized Comparison of Bypass Surgery versus Angioplasty
      Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease
      trial. Overall, 206 PCI-treated patients (26.3%) experienced at least 1
      readmission after the index procedure during 48.7 +/- 16.0 months of follow-up
      compared with 84 CABG-treated patients (14.8%, p <0.001). The most frequent
      causes of readmission were repeat revascularization after PCI (41%) and
      noncardiac readmissions after CABG (48%). Through repeated events analysis, PCI
      was associated with more frequent readmissions than CABG (hazard ratio 2.037, 95%
      confidence interval 1.542 to 2.692, p <0.001), being an independent predictor of
      readmission (hazard ratio 1.820, 95% confidence interval 1.420 to 2.331, p
      <0.001). Except for the acute period, defined as the first 3 months, when there
      was no significant difference in readmission rate, a higher readmission rate
      after PCI was consistently observed over the remainder of the follow-up period.
      In conclusion, PCI was shown to be associated with a higher risk of readmission
      than CABG in treating ULMCA disease. This higher risk was attributable to more
      frequent revascularization in the PCI group.

PMID- 24666620
TI  - Usefulness of a low CHADS2 or CHA2DS2-VASc score to predict normal diagnostic
      testing in emergency department patients with an acute exacerbation of previously
      diagnosed atrial fibrillation.
AB  - International guidelines do not specify what testing should be performed during
      emergency department (ED) evaluations for patients presenting with an
      exacerbation of previously diagnosed atrial fibrillation (AF). We hypothesized
      that low CHADS2 and CHA2DS2-VASc scores predict normal routine diagnostic testing
      in these patients. We conducted an analysis within a prospective observational
      cohort study at a university-affiliated hospital. We included patients with
      previously diagnosed AF and who presented to the ED primarily for an AF-related
      complaint. Logistic regression was used to analyze the association between CHADS2
      and CHA2DS2-VASc scores and abnormal results for blood counts, electrolytes,
      cardiac markers, thyroid function, and chest x-rays. We included 216 patients in
      this analysis. The odds ratios (95% confidence interval) for each point increase
      in CHADS2 for abnormal blood counts, electrolytes, troponin I, brain natriuretic
      peptide, thyroid function, and chest x-ray were 1.28 (0.99 to 1.65), 1.48 (1.19
      to 1.84), 1.42 (1.10 to 1.82), 1.66 (1.15 to 2.41), 0.95 (0.70 to 1.29), and 1.17
      (0.94 to 1.44), respectively. The corresponding odds ratios (95% confidence
      interval) for each point increase in CHA2DS2-VASc were 1.17 (0.96 to 1.42), 1.27
      (1.09 to 1.49), 1.30 (1.07 to 1.57), 1.57 (1.18 to 2.10), 0.98 (0.79 to 1.22),
      and 1.14 (0.97 to 1.33), respectively. Among ED patients with established AF who
      underwent evaluation for acutely symptomatic AF, nearly 3/4 of routine diagnostic
      tests return to normal. In conclusion, patients with CHADS2 or CHA2DS2-VASc score
      of 0 have the lowest likelihood of abnormal studies and may represent an easily
      identifiable group of patients who need fewer ED tests. 

PMID- 24666621
TI  - Carbon footprint and land requirement for dairy herd rations: impacts of feed
      production practices and regional climate variations.
AB  - Feed production is a significant source of greenhouse gas (GHG) emissions from
      dairy production and demands large arable and pasture acreage. This study
      analysed how regional conditions influence GHG emissions of dairy feed rations in
      a life cycle perspective, that is the carbon footprint (CF) and the land area
      required. Factors assessed included regional climate variations, grass/clover
      silage nutrient quality, feedstuff availability, crop yield and feed losses.
      Using the Nordic feed evaluation model NorFor, rations were optimised for
      different phases of lactation, dry and growing periods for older cows, first
      calvers and heifers by regional feed advisors and combined to annual herd
      rations. Feed production data at farm level were based on national statistics and
      studies. CF estimates followed standards for life cycle assessment and used
      emissions factors provided by IPCC. The functional unit was 'feed consumption to
      produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9
      900 kg ECM including replacement animals and feed losses'. Feed ration CF varied
      from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of
      total GHG emissions. Use of higher quality silage increased ration CF by up to 5%
      as a result of an additional cut and increased rates of synthetic N-fertiliser.
      Domestically produced horse bean (Vicia faba), by-products from the sugar
      industry and maize silage were included in the rations with the lowest CF, but
      horse bean significantly increased ration land requirement. Rations required
      between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg
      ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG
      emissions from land use change associated with Brazilian soya feed significantly
      increased ration CF. Ration CF and land use depended on ration composition, which
      was highly influenced by the regional availability and production of feedstuffs.
      The impact of individual feedstuffs on ration CF varies due to, for example,
      cultivation practices and climate conditions and feedstuffs should therefore be
      assessed in a ration and regional perspective before being used to decrease milk
      CF. Land use efficiency should be considered together with ration CF, as these
      can generate goal conflicts. 

PMID- 24666622
TI  - FNA cytology revealing Langerhans cell histiocytosis and papillary thyroid
      carcinoma.

PMID- 24666623
TI  - Duodenal switch versus Roux-en-Y gastric bypass for morbid obesity: systematic
      review and meta-analysis of weight results, diabetes resolution and early
      complications in single-centre comparisons.
AB  - Long-term weight loss after Roux-en-Y gastric bypass (RYGB) in super-obese
      patients has not been ideal. Biliopancreatic diversion with duodenal switch (DS)
      is argued to be better; however, additional side effects are feared. The aim of
      the present study was to determine differences in results after DS and RYGB in
      publications from single-centre comparisons. A systematic review of studies
      containing DS and RYGB performed at the same centre was performed. Outcome data
      were weight results, resolution of comorbid conditions, perioperative results and
      complications. Main outcome was difference in weight loss after DS and RYGB.
      Secondary outcomes were difference in resolution of comorbidities, perioperative
      results and complications. The final analysis included 16 studies with in total
      874 DS and 1,149 RYGB operations. When comparing weight results at the longest
      follow-up of each study, DS yielded 6.2 (95% confidence interval 5.0-7.5) body
      mass index units additional weight loss compared with RYGB, P < 0.001. Operative
      time and length of stay were significantly longer after DS, as well as the risk
      for post-operative leaks, P < 0.05. DS is more effective than RYGB as a weight
      reducing procedure. However, this comes at the price of more early complications
      and might also yield slightly higher perioperative mortality.

PMID- 24666624
TI  - Maturity indices in co-composting of chicken manure and sawdust with biochar.
AB  - Several maturity indices were evaluated for in-vessel co-composting of chicken
      manure and pine sawdust with three different biochars. All the seven mixtures
      (piles) contained chicken manure and sawdust. Six of these piles contained
      biochar; each biochar was added at two rates, 5% and 10% wet weight. The maturity
      of composts was assessed by C/N, dissolved organic carbon (DOC), seed
      germination, NO3(-)-N/NH4(+)-N, and the Solvita test. The C/N values of finished
      composts were from 31.5 to 35.7, which were much higher than the optimum value of
      21 for matured compost. Nevertheless, the rest of the parameters indicated that
      the composts were matured. The C/N values were high because of the high amount of
      recalcitrant carbon present in the feedstocks: biochar and sawdust. Biochar
      treated piles showed higher respiration as well as decomposition of DOC
      indicating higher microbial activity. Use of biochar in composting may reduce NH3
      emission and nitrate leaching. 

PMID- 24666625
TI  - Transcriptional responses of bacterial amoA gene to dimethyl sulfide inhibition
      in complex microbial communities.
AB  - This study presented an approach by combining the real-time reverse transcription
      polymerase chain reaction with the terminal restriction fragment length
      polymorphism (T-RFLP) to investigate transcriptional responses of ammonia
      oxidizing bacteria (AOB) to dimethyl sulfide (DMS) inhibition. Batch experiments
      with added ammonium and DMS were conducted using three activated sludges and
      Nitrosomonas europaea, and the transcriptional responses of the amo subunit A
      (amoA) mRNA were evaluated. It was found that DMS inhibited ammonium oxidation
      and amoA mRNA expression in all batch experiments but the inhibition degree
      observed was different for different sludges examined. It is likely that the
      different inhibitory effects of DMS on ammonium oxidation and amoA mRNA
      expression stemmed from different dominant AOB populations in the sludges. The T
      RFLP results for amoA mRNA suggested that inhibition of ammonium oxidation by DMS
      to Nm. europaea-like AOB with T-RF 219/270 is relatively minor compared to other
      AOB populations in the examined sludges, such as Nm. europaea-like AOB with T-RF
      491/491. 

PMID- 24666626
TI  - Trace element supplementation in the biogas production from wheat stillage-
      optimization of metal dosing.
AB  - A trace element dosing strategy for the anaerobic digestion of wheat stillage was
      developed in this study. Mesophilic CSTR reactors were operated with the sulfuric
      substrate wheat stillage in some cases under trace element deficiency. After
      supplementing trace elements during the start-up, one of the elements of Fe, Ni,
      Co, Mo, and W were depleted in one digester while still augmenting the other
      elements to determine minimum requirements for each element. The depletion of Fe
      and Ni resulted in a rapid accumulation of volatile fatty acids while Co and W
      seem to have a long-term effect. Based on the results it was possible to reduce
      the dosing of trace elements, which is positive with reference to economic and
      environmental aspects. 

PMID- 24666627
TI  - Oral health in Libya: addressing the future challenges.
AB  - Libya is a vast country situated in North Africa, having a relatively better
      functioning economy with a scanty population. This article is the first known
      attempt to review the current state of oral health care in Libya and to explore
      the present trends and future challenges. Libyan health system, oral health care,
      and human resources with the present status of dental education are reviewed
      comprehensively. A bibliographic study of oral health research and publications
      has been carried out. The results point toward a common indicator that oral
      health-related research is low. Strategies have to be developed to educate the
      medical and dental professionals, to update the current curriculum and enable the
      system to be competent in all aspects of oral health care management. 

PMID- 24666628
TI  - Benzodiazepine discontinuation and patient outcome in a chronic geriatric
      medical/psychiatric unit: a retrospective chart review.
AB  - AIM: A substantial number of elderly patients take benzodiazepines (BZD)
      regularly despite concerns about toxicity and possible dependence, and there are
      relatively few data to guide clinicians' decisions regarding discontinuing
      benzodiazepines in the elderly. METHODS: We carried out a retrospective chart
      review of 75 elderly patients admitted to a chronic medical/psychiatric unit who
      were taking a standing dose of benzodiazepines on admission, comparing 40
      patients who discontinued benzodiazepines versus 35 who did not discontinue.
      PURPOSE: We examined the association of BZD discontinuation versus continuation
      with clinical outcomes on discharge, and further examined clinical
      characteristics associated with BZD discontinuation. RESULTS: Discontinuers had
      shorter length of stay without evidence of worse cognitive and functional outcome
      except a trend toward increased incidence of agitation. Logistic regression
      models suggested anxiety, higher age and higher dose of antidepressants at the
      beginning were significantly related to successful discontinuation during
      admission after regression. CONCLUSION: These data imply that BZD withdrawal
      during admission can be safe and feasible in many elderly frail patients, and
      that withdrawal might be associated with shorter duration of chronic
      hospitalization.

PMID- 24666629
TI  - The Fukushima-137Cs deposition case study: properties of the multi-model
      ensemble.
AB  - In this paper we analyse the properties of an eighteen-member ensemble generated
      by the combination of five atmospheric dispersion modelling systems and six
      meteorological data sets. The models have been applied to the total deposition of
      (137)Cs, following the nuclear accident of the Fukushima power plant in March
      2011. Analysis is carried out with the scope of determining whether the ensemble
      is reliable, sufficiently diverse and if its accuracy and precision can be
      improved. Although ensemble practice is becoming more and more popular in many
      geophysical applications, good practice guidelines are missing as to how models
      should be combined for the ensembles to offer an improvement over single model
      realisations. We show that the ensemble of models share large portions of bias
      and variance and make use of several techniques to further show that subsets of
      models can explain the same amount of variance as the full ensemble mean with the
      advantage of being poorly correlated, allowing to save computational resources
      and reduce noise (and thus improving accuracy). We further propose and discuss
      two methods for selecting subsets of skilful and diverse members, and prove that,
      in the contingency of the present analysis, their mean outscores the full
      ensemble mean in terms of both accuracy (error) and precision (variance). 

PMID- 24666630
TI  - Cooperative personalities and social niche specialization in female meerkats.
AB  - The social niche specialization hypothesis predicts that group-living animals
      should specialize in particular social roles to avoid social conflict, resulting
      in alternative life-history strategies for different roles. Social niche
      specialization, coupled with role-specific life-history trade-offs, should thus
      generate between-individual differences in behaviour that persist through time,
      or distinct personalities, as individuals specialize in particular nonoverlapping
      social roles. We tested for support for the social niche specialization
      hypothesis in cooperative personality traits in wild female meerkats (Suricata
      suricatta) that compete for access to dominant social roles. As cooperation is
      costly and dominance is acquired by heavier females, we predicted that females
      that ultimately acquired dominant roles would show noncooperative personality
      types early in life and before and after role acquisition. Although we found
      large individual differences in repeatable cooperative behaviours, there was no
      indication that individuals that ultimately acquired dominance differed from
      unsuccessful individuals in their cooperative behaviour. Early-life behaviour did
      not predict social role acquisition later in life, nor was cooperative behaviour
      before and after role acquisition correlated in the same individuals. We suggest
      that female meerkats do not show social niche specialization resulting in
      cooperative personalities, but that they exhibit an adaptive response in
      personality at role acquisition. 

PMID- 24666631
TI  - Soya protein stimulates bile acid excretion by the liver and intestine through
      direct and indirect pathways influenced by the presence of dietary cholesterol.
AB  - Several studies using different animal models have demonstrated that the
      consumption of soya protein (SP) reduces serum cholesterol concentrations by
      increasing the excretion of bile acids (BA). However, the mechanism by which SP
      enhances BA excretion is not fully understood. Therefore, the aim of the present
      study was to determine whether the consumption of SP regulates the expression of
      key enzymes involved in hepatic BA synthesis and the transporters involved in
      reverse cholesterol transport (RCT) via fibroblast growth factor 15 (FGF15)
      and/or small heterodimer protein (SHP) in rats. To achieve this aim, four groups
      of rats were fed experimental diets containing 20 % casein (C) or SP with or
      without the addition of 0.2 % cholesterol and the expression of hepatic genes
      involved in BA synthesis and the ileal and hepatic RCT was measured. Rats fed the
      SP diet had higher concentrations of ileal FGF15 and hepatic FGF15 receptor
      (FGFR4) and increased expression of SHP and liver receptor homolog 1 (LRH1) than
      those fed the C diet; as a result, the excretion of faecal BA was greater. The
      addition of cholesterol to the diet repressed the protein abundance of FGF15 and
      FGFR4; however, SP increased the expression of SHP and LRH1 to a lesser extent.
      Nonetheless, the expression of ABCG5/8 was increased in the intestine of rats fed
      the SP diet, and the effect was enhanced by the addition of cholesterol to the
      diet. In conclusion, SP in the presence of cholesterol increases BA synthesis via
      the repressions of FGF15 and SHP and accelerates BA excretion to prevent
      cholesterol overload in the enterocytes by increasing RCT.

PMID- 24666632
TI  - Children of Senegal River Basin show the highest prevalence of Blastocystis sp.
      ever observed worldwide.
AB  - BACKGROUND: Blastocystis sp. is currently the most common intestinal protist
      found in human feces and considered an emerging parasite with a worldwide
      distribution. Because of its potential impact in public health, we reinforced the
      picture of Blastocystis sp. prevalence and molecular subtype distribution in
      Africa by performing the first survey of this parasite in Senegal. METHODS: Stool
      samples from 93 symptomatic presenting with various gastrointestinal disorders or
      asymptomatic children living in three villages of the Senegal River Basin were
      tested for the presence of Blastocystis sp. by non-quantitative and quantitative
      PCR using primer pairs targeting the SSU rDNA gene. Positive samples were
      subtyped to investigate the frequency of Blastocystis sp. subtypes in our cohort
      and the distribution of subtypes in the symptomatic and asymptomatic groups of
      children. RESULTS: By the use of molecular tools, all 93 samples were found to be
      positive for Blastocystis sp. indicating a striking parasite prevalence of 100%.
      Mixed infections by two or three subtypes were identified in eight individuals.
      Among a total of 103 subtyped isolates, subtype 3 was most abundant (49.5%)
      followed by subtype 1 (28.2%), subtype 2 (20.4%) and subtype 4 (1.9%). Subtype 3
      was dominant in the symptomatic group while subtypes 1 and 2 were detected with
      equal frequency in both symptomatic and asymptomatic groups. The distribution of
      subtypes was compared with those available in other African countries and
      worldwide. Comparison confirmed that subtype 4 is much less frequently detected
      or absent in Africa while it is commonly found in Europe. Potential sources of
      Blastocystis sp. infection including human-to-human, zoonotic, and waterborne
      transmissions were also discussed. CONCLUSIONS: The prevalence of Blastocystis
      sp. in our Senegalese population was the highest prevalence ever recovered
      worldwide for this parasite by reaching 100%. All cases were caused by subtypes
      1, 2, 3 and 4 with a predominance of subtype 3. More than half of the children
      infected by Blastocystis sp. presented various gastrointestinal disorders. Such
      high prevalence of blastocystosis in developing countries makes its control a
      real challenge for public health authorities.

PMID- 24666633
TI  - A community based prevention of weight gain intervention (Mothers In Motion)
      among young low-income overweight and obese mothers: design and rationale.
AB  - BACKGROUND: Over 45% of American women 20-39 years old are at risk for type 2
      diabetes, cardiovascular disease, and other health conditions because they are
      overweight or obese. The prevalence of overweight and obesity is
      disproportionately high among low-income women. This paper describes the study
      design and rationale of a community based intervention (Mothers In Motion, MIM)
      aimed to prevent weight gain among low-income overweight and obese mothers 18-39
      years old by promoting stress management, healthy eating, and physical activity.
      METHODS/DESIGN: Peer recruiters approach participants from 5 Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) in Michigan. The MIM
      delivers theory-based, culturally-sensitive intervention messages via a
      combination of DVDs and peer support group teleconferences (PSGTs). The DVD
      features African American and white overweight and obese WIC mothers who
      participated in a healthy lifestyle intervention patterned after MIM. The PSGTs
      are led by paraprofessionals from Michigan State University Extension and WIC
      providers in Michigan who are trained in motivational interviewing and group
      facilitation skills. Participants are randomly assigned to an intervention
      (n=350) or comparison group (n=175). The intervention group receives a 16-week
      intervention on a weekly or bi-weekly basis. Participants are asked to watch 10
      MIM DVD chapters at home and join 10 PSGT sessions by phone. The comparison group
      receives printed educational materials. The primary outcome is body weight.
      Secondary outcomes include dietary fat, fruit, and vegetable intake; physical
      activity; stress, and affect. Mediators are self-efficacy, emotional coping
      response, social support, and autonomous motivation. Telephone interviews and in
      person data collection at WIC offices occur at 3 time points: baseline,
      immediately, and 3 months after the 16-week intervention. DISCUSSION: If MIM
      shows effectiveness, it could have a favorable impact on public health and
      community programs. The DVDs and PSGTs will be disseminated in WIC, Extension,
      clinical practice that promote healthy lifestyles for similar target audiences to
      make a broad contribution to the prevention of weight gain in low-income mothers.
      Also, our methodology can be adapted by researchers and community stakeholders to
      help other low-income populations prevent weight gain. TRIAL REGISTRATION:
      Clinical Trials Number: NCT01839708.

PMID- 24666634
TI  - Reprint of "Methylmercury production in and export from agricultural wetlands in
      California, USA: the need to account for physical transport processes into and
      out of the root zone".
AB  - Concentration and mass balance analyses were used to quantify methylmercury
      (MeHg) loads from conventional (white) rice, wild rice, and fallowed fields in
      northern California's Yolo Bypass. These analyses were standardized against
      chloride to distinguish transport pathways and net ecosystem production (NEP).
      During summer, chloride loads were both exported with surface water and moved
      into the root zone at a 2:1 ratio. MeHg and dissolved organic carbon (DOC)
      behaved similarly with surface water and root zone exports at ~3:1 ratio. These
      trends reversed in winter with DOC, MeHg, and chloride moving from the root zone
      to surface waters at rates opposite and exceeding summertime root zone fluxes.
      These trends suggest that summer transpiration advectively moves constituents
      from surface water into the root zone, and winter diffusion, driven by
      concentration gradients, subsequently releases those constituents into surface
      waters. The results challenge a number of paradigms regarding MeHg. Specifically,
      biogeochemical conditions favoring microbial MeHg production do not necessarily
      translate to synchronous surface water exports; MeHg may be preserved in the
      soils allowing for release at a later time; and plants play a role in both
      biogeochemistry and transport. Our calculations show that NEP of MeHg occurred
      during both summer irrigation and winter flooding. Wild rice wet harvesting and
      winter flooding of white rice fields were specific practices that increased MeHg
      export, both presumably related to increased labile organic carbon and
      disturbance. Outflow management during these times could reduce MeHg exports.
      Standardizing MeHg outflow:inflow concentration ratios against natural tracers
      (e.g. chloride, EC) provides a simple tool to identify NEP periods. Summer MeHg
      exports averaged 0.2 to 1MUgm(-2) for the different agricultural wetland fields,
      depending upon flood duration. Average winter MeHg exports were estimated at
      0.3MUgm(-2). These exports are within the range reported for other shallow
      aquatic systems. 

PMID- 24666635
TI  - Seroprevalence of flaviviruses antibodies in water buffaloes (Bubalus bubalis) in
      Brazilian Amazon.
AB  - BACKGROUND: The state of Para encompasses 26% of Brazilian Amazon where an
      enormous diversity of arboviruses has been found. This study aimed to assess the
      prevalence and distribution of hemagglutination-inhibition antibodies against
      antigens of six Flavivirus (yellow fever virus, Ilheus virus, Saint Louis
      encephalitis virus, Cacipacore virus, Bussuquara virus and Rocio virus) in water
      buffaloes in Para state, Brazil. The prevalence of antibodies in these farm
      animals is important to determine the circulating arboviruses. FINDINGS: All
      investigated arboviruses were detected in the species studied and our results
      indicate that water buffaloes are susceptible to Flavivirus infection.
      Furthermore, there is solid evidence of active circulation of these viruses in
      the Brazilian Amazon. CONCLUSIONS: Water buffaloes showed higher prevalence of
      heterotypic antibody reactions and we hypothesized that they can serve as
      sentinels to detect the movement of such arboviruses in the Brazilian Amazon.

PMID- 24666636
TI  - Complex regional pain syndrome in a young athlete with von Willebrand disease.
AB  - A 17-year-old female with type 1 Von Willebrand Disease (vWD) developed left
      medial calf pain while running track. Over the next 6 months, orthopedic surgery,
      sports medicine, vascular surgery, and neurology treated her under various
      working diagnoses; however, the pain, allodynia, coldness, and pale skin color
      worsened. She was admitted to a tertiary pediatric hospital for intractable pain
      where PM&R diagnosed her with complex regional pain syndrome (CRPS) type 1, began
      gabapentin, and initiated an aggressive inpatient rehabilitation program. During
      her 3 weeks of inpatient rehabilitation, passive range of motion of knee
      extension improved from 40 degrees  from extension to full extension, and ankle
      dorsiflexion improved from 15 degrees  from neutral to a consistent range of
      motion beyond neutral. Additional outcome measures were distance of ambulation
      and assistive device usage; from admission to inpatient rehabilitation to 2
      months postdischarge, her weight-bearing tolerance progressed from nonweight
      bearing to partial weight-bearing, and ambulation improved from 20 feet with a
      three-point crutch gait to unlimited distances with a four-point crutch gait.
      This is the first known case of a bleeding disorder as the likely underlying
      microvascular pathology associated with CRPS, a theory exposed in 2010. 

PMID- 24666637
TI  - Production of somatic cell nuclear transfer embryos using in vitro-grown and in
      vitro-matured oocytes in rabbits.
AB  - We examined growing oocytes collected from follicles remaining in superovulated
      rabbit ovaries, that were grown (in vitro growth, IVG) and matured (in vitro
      maturation, IVM) in vitro. We produced somatic cell nuclear transfer (SCNT)
      embryos using the mature oocytes and examined whether these embryos have the
      ability to develop to the blastocyst stage. In addition, we examined the effects
      of trichostatin A (TSA), a histone deacetylase inhibitor (HDACi), on the
      developmental competence of SCNT embryos derived from IVG-IVM oocytes. After
      growth for 7 days and maturation for 14-16 h in vitro, the growing oocytes
      reached the metaphase II stage (51.4%). After SCNT, these reconstructed embryos
      reached the blastocyst stage (20%). Furthermore, the rate of development to the
      blastocyst stage and the number of cells in the blastocysts in SCNT embryos
      derived from IVG-IVM oocytes were significantly higher for TSA-treated embryos
      compared with TSA-untreated embryos (40.6 versus 21.4% and 353.1 +/- 59.1 versus
      202.5 +/- 54.6, P < 0.05). These results indicate that rabbit SCNT embryos using
      IVG-IVM oocytes have the developmental competence to reach the blastocyst stage. 

PMID- 24666638
TI  - A novel early precursor cell population from rat bone marrow promotes
      angiogenesis in vitro.
AB  - BACKGROUND: Some studies demonstrated therapeutic angiogenesis attributable to
      the effects of endothelial progenitor cells (EPC), others have reported
      disappointing results. This may be due to the fact that EPC populations used in
      these contradictory studies were selected and defined by highly variable and
      differing experimental protocols. Indeed, the isolation and reliable
      characterization of ex vivo differentiated EPC raises considerable problems due
      to the fact there is no biomarker currently available to specifically identify
      EPC exclusively. On the other hand traditional differentiation of primary
      immature bone marrow cells towards the endothelial lineage is a time-consuming
      process of up to 5 weeks. To circumvent these shortcomings, we herein describe a
      facile method to isolate and enrich a primary cell population from rat bone
      marrow, combining differential attachment methodology with cell sorting
      technology. RESULTS: The combination of these techniques enabled us to obtain a
      pure population of early endothelial precursor cells that show homogenous
      upregulation of CD31 and VEGF-R2 and that are positive for CD146. These cells
      exhibited typical sprouting on MatrigelTM. Additionally, this population
      displayed endothelial tube formation when resuspended in MatrigelTM as well as in
      fibrin glue, demonstrating its functional angiogenic capacity. Moreover, these
      cells stained positive for DiI-ac-LDL and FITC-UEA, two markers that are commonly
      considered to stain differentiating EPCs. Based upon these observations in this
      study we describe a novel and time-saving method for obtaining a pure endothelial
      precursor cell population as early as 2-3 weeks post isolation that exhibits
      endothelial abilities in vitro and which still might have retained its early
      endothelial lineage properties. CONCLUSION: The rapid isolation and the high
      angiogenic potential of these syngeneic cells might facilitate and accelerate the
      pre-vascularization of transplanted tissues and organs also in a human setting in
      the future.

PMID- 24666639
TI  - Role of non-coding RNAs in pancreatic beta-cell development and physiology.
AB  - The progression of diabetes is accompanied by increasing demand to the beta-cells
      to produce and secrete more insulin, requiring complex beta-cell adaptations.
      Functionally active and ubiquitous non-coding RNAs (ncRNAs) have the capacity to
      take part in such adaptations as they have been shown to be key regulatory
      molecules in various biological processes. In the pancreatic islets, the function
      of ncRNAs and their contribution to disease development is beginning to be
      understood. Here, we review the different classes of ncRNAs, such as long non
      coding RNAs (lncRNAs) and microRNAs (miRNAs), and their potential contribution to
      insulin secretion. A special focus will be on miRNAs and their regulatory
      function in beta-cell physiology and insulin exocytosis. As important players in
      gene regulation, ncRNAs have huge potential in opening innovative therapeutic
      avenues against diabetes and associated complications. 

PMID- 24666640
TI  - Perineal approach for a gastrointestinal stromal tumor on the anterior wall of
      the lower rectum.
AB  - BACKGROUND: Wide margins of resection and regional lymphadenectomy for GIST are
      not necessary. Several procedures for rectal GIST have been designed according to
      the location and size of the tumor to preserve the anal function and decrease the
      morbidity rate. CASE PRESENTATION: We report a 61-year-old-man with rectal
      bleeding. Proctologic examination revealed a small mass of approximately 2 cm in
      diameter on the anterior wall of the rectum at a distance of 4 cm from the anal
      verge. Histological examination of the biopsy sample via the rectum led to a
      diagnosis of GIST due to immunohistochemical positivity for C117 and CD34.
      Perineal resection was planned because abdominoperineal resection with
      sacrificing the sphincter function was excessive for this small tumor, and low
      anterior resection with the double stapling technique was difficult due to the
      lower position. A hemispheric incision was made from one mid-ischial tuberosity
      to the other with an apex of approximately 2 cm above the anus. The fascia band
      and muscles were successively transected in order to expose the anterior wall of
      the rectum, and excision of the tumor was performed. The postoperative course was
      uneventful, and the patient remained free from incontinence and recurrence.
      CONCLUSIONS: This perineal approach for a GIST on the anterior wall of the rectum
      is one option for preserving the anal function and decreasing the morbidity rate.

PMID- 24666641
TI  - The perceptions of nurses towards barriers to the safe administration of
      medicines in mental health settings.
AB  - The purpose of this study was to investigate perceptions of barriers to safe
      administration of medicines in mental health settings. A cross-sectional survey
      was used, and 70 mental health nurses and 41 students were recruited from a
      mental health trust and a university in Yorkshire, UK. Respondents completed a
      questionnaire comprising closed- and open-response questions. One item, which
      contained seven sub-items, addressed barriers to safe administration of
      medication. Seven themes--five nurse- and prescriber-focused and two service user
      focused--were abstracted from the data, depicting a range of barriers to safe
      administration of medicines. Nurse- and prescriber-focused themes included
      environmental distractions, insufficient pharmacological knowledge, poorly
      written and incomplete medication documentation, inability to calculate
      medication dosage correctly, and work-related pressure. Service user-focused
      themes comprised poor adherence to medication regimens, and cultural and
      linguistic communication barriers with service users. Tackling medication
      administration error is predominantly an organizational rather than individual
      practitioner responsibility.

PMID- 24666642
TI  - Primary Langerhans cell histiocytosis of the thyroid gland: role of langerin in
      FNA cytological diagnosis.

PMID- 24666643
TI  - Release of monocyte migration signals by breast cancer cell lines after ablative
      and fractionated gamma-irradiation.
AB  - BACKGROUND: Radiotherapy, administered in fractionated as well as ablative
      settings, is an essential treatment component for breast cancer. Besides the
      direct tumor cell death inducing effects, there is growing evidence that immune
      mechanisms contribute - at least in part - to its therapeutic success. The
      present study was designed to characterize the type and the extent of cell death
      induced by fractionated and ablative radiotherapy as well as its impact on the
      release of monocyte migration stimulating factors by dying breast cancer cells.
      METHODS: Cell death and senescence assays were employed to characterize the
      response of a panel of breast cancer cell lines with different receptor and p53
      status towards gamma-irradiation applied in a fractionated (daily doses of 2 Gy)
      or ablative setting (single dose of 20 Gy). Cell-free culture supernatants were
      examined for their monocyte migration stimulating potential in transwell
      migration and 2D chemotaxis/chemokinesis assays. Irradiation-induced
      transcriptional responses were analyzed by qRT-PCR, and CD39 surface expression
      was measured by flow cytometry. RESULTS: Fast proliferating, hormone receptor
      negative breast cancer cell lines with defective p53 predominantly underwent
      primary necrosis in response to gamma-irradiation when applied at a single,
      ablative dose of 20 Gy, whereas hormone receptor positive, p53 wildtype cells
      revealed a combination of apoptosis, primary, and secondary (post-apoptotic)
      necrosis. During necrosis the dying tumor cells released apyrase-sensitive
      nucleotides, which effectively stimulated monocyte migration and chemokinesis. In
      hormone receptor positive cells with functional p53 this was hampered by
      irradiation-induced surface expression of the ectonucleotidase CD39. CONCLUSIONS:
      Our study shows that ablative radiotherapy potently induces necrosis in fast
      proliferating, hormone receptor negative breast cancer cell lines with mutant
      p53, which in turn release monocyte migration and chemokinesis stimulating
      nucleotides. Future studies have to elucidate, whether these mechanisms might be
      utilized in order to stimulate intra-tumoral monocyte recruitment and subsequent
      priming of adaptive anti-tumor immune responses, and which breast cancer subtypes
      might be best suited for such approaches.

PMID- 24666644
TI  - Comparative metagenomic analyses reveal viral-induced shifts of host metabolism
      towards nucleotide biosynthesis.
AB  - BACKGROUND: Viral genomes often contain metabolic genes that were acquired from
      host genomes (auxiliary genes). It is assumed that these genes are fixed in viral
      genomes as a result of a selective force, favoring viruses that acquire specific
      metabolic functions. While many individual auxiliary genes were observed in viral
      genomes and metagenomes, there is great importance in investigating the abundance
      of auxiliary genes and metabolic functions in the marine environment towards a
      better understanding of their role in promoting viral reproduction. RESULTS: In
      this study, we searched for enriched viral auxiliary genes and mapped them to
      metabolic pathways. To initially identify enriched auxiliary genes, we analyzed
      metagenomic microbial reads from the Global Ocean Survey (GOS) dataset that were
      characterized as viral, as well as marine virome and microbiome datasets from the
      Line Islands. Viral-enriched genes were mapped to a "global metabolism network"
      that comprises all KEGG metabolic pathways. Our analysis of the viral-enriched
      pathways revealed that purine and pyrimidine metabolism pathways are among the
      most enriched pathways. Moreover, many other viral-enriched metabolic pathways
      were found to be closely associated with the purine and pyrimidine metabolism
      pathways. Furthermore, we observed that sequential reactions are promoted in
      pathways having a high proportion of enriched genes. In addition, these enriched
      genes were found to be of modular nature, participating in several pathways.
      CONCLUSIONS: Our naive metagenomic analyses strongly support the well-established
      notion that viral auxiliary genes promote viral replication via both degradation
      of host DNA and RNA as well as a shift of the host metabolism towards nucleotide
      biosynthesis, clearly indicating that comparative metagenomics can be used to
      understand different environments and systems without prior knowledge of pathways
      involved.

PMID- 24666645
TI  - Alternative intrapopulation life-history strategies and their trade-offs in an
      African annual fish.
AB  - In ephemeral habitats, the same genotypes cope with unpredictable environmental
      conditions, favouring the evolution of developmental plasticity and alternative
      life-history strategies (ALHS). We tested the existence of intrapopulation ALHS
      in an annual killifish, Nothobranchius furzeri, inhabiting temporary pools. The
      pools are either primary (persisting throughout the whole rainy season) or
      secondary (refilled after desiccation of the initial pool), representing
      alternative niches. The unpredictable conditions led to the evolution of
      reproductive bet-hedging with asynchronous embryonic development. We used a
      common garden experiment to test whether the duration of embryonic period is
      associated with post-embryonic life-history traits. Fish with rapid embryonic
      development (secondary pool strategy, high risk of desiccation) produced
      phenotypes with more rapid life-history traits than fish with slow embryonic
      development (primary pool strategy). The fast fish were smaller at hatching but
      had larger yolk sac reserves. Their post-hatching growth was more rapid, and they
      matured earlier. Further, fast fish grew to a smaller body size and died earlier
      than slow fish. No differences in fecundity, propensity to mate or physiological
      ageing were found, demonstrating a combination of plastic responses and
      constraints. Such developmentally related within-population plasticity in life
      history is exceptional among vertebrates. 

PMID- 24666646
TI  - Thiophene carboxamide inhibitors of JAK2 as potential treatments for
      myleoproliferative neoplasms.
AB  - A series of carboxamide-substituted thiophenes demonstrating inhibition of JAK2
      is described. Development of this chemical series began with the bioisosteric
      replacement of a urea substituent by a pyridyl ring. Issues of chemical and
      metabolic stability were solved using the results of both in vitro and in vivo
      studies, ultimately delivering compounds such as 24 and 25 that performed well in
      an acute PK/PD model measuring p-STAT5 inhibition. 

PMID- 24666647
TI  - Novel chlorantraniliprole derivatives as potential insecticides and probe to
      chlorantraniliprole binding site on ryanodine receptor.
AB  - The lepidopteran pests such as diamondback moth are the regularly harmful pests
      of crops in the world, which brings enormous losses in crop production.
      Chlorantraniliprole is an anthranilic diamide insecticide registered for the
      control of lepidopteran pests with high insecticidal activity, however with
      uncertain binding site action target of chlorantraniliprole on ryanodine
      receptor, a series of new chlorantraniliprole derivatives were synthesized and
      the insecticidal activities of these compounds against diamondback moth were
      evaluated with chlorantraniliprole and indoxacarb as control. All compounds
      except 8h, 8p and 8t exhibited varying degree of activities against diamondback
      moth. Especially, compounds 8c, 8i, 8k and 8l displayed good insecticidal
      activities against diamondback moth and the activities are even better than that
      of indoxacarb during 72 h period. The Ki values of all synthesized compounds were
      calculated through autodocking program respectively. The relationship between
      calculation value of molecular docking and results of insecticidal activities
      indicated that the proposed specific receptor, the membrane-spanning domain
      protein of diamondback moth ryanodine receptor in our study might have
      chlorantraniliprole binding sites.

PMID- 24666648
TI  - Bexarotene prodrugs: targeting through cleavage by NQO1 (DT-diaphorase).
AB  - Bexarotene, a retinoid X receptor (RXR) agonist, is being tested as a potential
      disease modifying treatment for neurodegenerative conditions. To limit the
      peripheral exposure of bexarotene and release it only in the affected areas of
      the brain, we designed a prodrug strategy based on the enzyme NAD(P)H/quinone
      oxidoreductase (NQO1) that is elevated in neurodegenerative diseases. A series of
      indolequinones (known substrates of NQO1) was synthesized and coupled to
      bexarotene. Bexarotene-3-(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7
      dione ester 7a was cleaved best by NQO1. The prodrugs are not cleaved by
      esterase. 

PMID- 24666649
TI  - Reversal of new, factor-specific oral anticoagulants by rFVIIa, prothrombin
      complex concentrate and activated prothrombin complex concentrate: a review of
      animal and human studies.
AB  - INTRODUCTION: Recombinant activated factor VII (rFVIIa), prothrombin complex
      concentrate (PCC) and activated PCC (aPCC) are three non-specific haemostatic
      agents sometimes employed to reverse new, factor-specific oral anticoagulants.
      METHODS: We conducted a review in the literature to compare the abilities of
      rFVIIa, PCC and aPCC to reverse factor-specific anticoagulants. MEDLINE and
      EMBASE databases were searched up to Oct 2013. RESULTS: Eleven animal studies and
      two human trials met predefined inclusion criteria. To account for dosing
      variations of anticoagulants among studies, data were interpreted based on
      standards referenced from human trials at therapeutic doses. In animal studies,
      inconsistencies in the reversal abilities of rFVIIa, PCC and aPCC can be partly
      attributed to inter-species differences in the affinity among various clotting
      factors and tissue factors. Moreover, the differences in the affinity between
      species-specific clotting factors and anticoagulants that were initially designed
      to inhibit human factor may impose additional obstacles when comparing single
      factor rFVIIa with agents that contained multiple clotting factors. In the
      absence of a common clinical indication for the utilization of rFVIIa, PCC and
      aPCC, it is difficult, if not impossible, to establish an equivalent dose among
      these haemostatic agents when comparing their effectiveness in reversing factor
      specific oral anticoagulants. Human trials were too few and sub-optimally
      designed to draw definite conclusions. CONCLUSION: While preclinical studies may
      hint at a role for these haemostatic agents in reversing the anticoagulant
      effects of oral, factor-specific anticoagulants, existing trials offer
      inconclusive evidence to guide a clinical decision among individual agents with
      respect to potency and thrombosis risk. The mechanistic differences of these
      hemostatic agents in terms of their interactions with other coagulation factors
      impose major obstacles for the scientists using animal models to compare the
      efficacy of these reversal agents.

PMID- 24666650
TI  - Is the Cambridge Cognitive Examination - revised a good tool for detection of
      dementia in illiterate Brazilian older adults?
AB  - AIMS: Few studies have been published on the use of the Cambridge Cognitive
      Examination Test - Revised (CAMCOG-R) for cognitive assessment of low educational
      level older adults. The aim of the present study was to determine the accuracy of
      the Brazilian version of the CAMCOG-R (Br-CAMCOG-R) within a sample of low
      educational level and illiterate older adults. METHODS: The Br-CAMCOG-R was
      administered to outpatients in a public geriatric clinic. The diagnosis of
      dementia was based on the Diagnostic and Statistical Manual of Mental Disorders
      Fourth Edition criteria. The receiving operator characteristic curves were
      plotted, and the best trade-offs between sensitivities and specificities were
      calculated. RESULTS: A total of 189 participants were evaluated. The mean age was
      77 +/- 6.9 years. The mean educational level was 3.1 +/- 2.2 years. The mean test
      score was 66.5 +/- 13.1 points; there were 56 (29.6%) participants with dementia.
      The best cut-off score for illiterate participants was 50/51; sensitivity,
      specificity and area under the curve (AUC) were 69%, 69% and 0.75, respectively;
      for participants with a low educational level, the best cut-off point was 60/61;
      the sensitivity, specificity and AUC were 83%, 85%, and 0.93, respectively; for
      participants with a middle educational level, the best cut-off point was 69/70;
      the sensitivity, specificity and AUC were 90%, 76% and 0.91, respectively.
      CONCLUSIONS: The Br-CAMCOG-R was useful for identifying cases of dementia among
      older adults with middle and low levels of literacy, but inadequate for the
      illiterate individuals.

PMID- 24666651
TI  - Cardiotoxicity and oncological treatments.
AB  - BACKGROUND: Cardiotoxic and other side effects limit the usefulness of treatments
      for cancer. METHOD: This article is based on pertinent articles that were
      retrieved by a selective search in PubMed and other databases, and on the
      guidelines of the European Society of Cardiology, the Association of Scientific
      Medical Societies in Germany, and the European Society of Medical Oncology.
      RESULTS: Prospective studies have shown that some treatments for cancer are
      cardiotoxic. The heart damage that they cause can manifest itself as arrhythmia,
      arterial hypertension, thromboembolism, angina pectoris, myocardial infarction,
      or heart failure. It has been observed that potentially lethal complications can
      arise as late as 40 years after treatment of the original cancer. The
      anthracycline drug doxorubicin, given in a dose of 500 mg/m2 of body surface
      area, has been found to cause cardiac complications in 4-36% of the patients
      treated with it. Trastuzumab and epirubicin cause dose-limiting cardiac events in
      1.7-5% of patients, depending on the dosage. Paclitaxel causes bradycardia,
      intracardiac conduction block, or arrhythmia in 0.5% of patients. 18% of patients
      treated with sunitimib or sorafenib have clinical manifestations relating to the
      heart (angina pectoris, dyspnea). 5-fluorouracil can cause angina pectoris at the
      beginning of treatment and rarely causes myocardial infarction. Cardiac radiation
      therapy, a form of treatment practiced in earlier decades, can cause cardiac
      complications 20 years after the event. The opportunity to prevent cardiac
      complications of anthracycline drugs with dexrazoxane is decidedly limited, but
      initial studies have shown that treatment with beta-blockers and ACE inhibitors
      lessens the likelihood of cardiotoxic side effects. When cardiac complications
      arise, the generally applicable rules for the treatment of each type of cardiac
      problem should be followed. The oncological treatment protocol should be adjusted
      or switched to one that is less damaging to the heart. CONCLUSION: Treating
      physicians need to be thoroughly acquainted with the cardiotoxic effects of anti
      cancer drugs so that they can diagnose them early on and avoid jeopardizing the
      overall success of treatment.

PMID- 24666652
TI  - Nodular goiter: cautious indications for surgery.

PMID- 24666654
TI  - Rekindling the role of nurses in patients' oral nutrition.
AB  - Hospital malnutrition is a worldwide problem. A nutritional care policy was
      evaluated to determine whether nutrition was enhanced by improving patients'
      access and nurses' supervision of meals. Fourteen pre-audit wards (435 patients)
      and 20 postaudit wards (422 patients) across three hospitals participated in a
      pre-post audit and observation study with an examination of documentation. A food
      satisfaction survey was completed by 226 patients (pre) and 240 patients (post).
      A modest increase in the proportion of patients receiving supervision with meals
      (83% pre, 88% post, P = 0.058) was not associated with an increase in consumption
      (50% or more of meal). Patients report poor appetite in the presence of good to
      fair food quality. The nurse's role in nutritional care was defined. Protected
      mealtimes supported by nurse managers reorganizing staff mealtimes with
      assistance from carers, volunteers and other health professionals were endorsed.
      Nurses must ensure that patient's meal trays are accessible. 

PMID- 24666653
TI  - The surgical treatment of bilateral benign nodular goiter: balancing invasiveness
      with complications.
AB  - BACKGROUND: About 100,000 thyroid operations are performed in Germany each year.
      There is a current trend toward more radical surgery for bilateral euthyroid
      nodular goiter. In recent years, thyroid specialists and specialty guidelines
      have recommended total thyroidectomy, because it ensures that nodules will not
      recur and already provides an adequately radical excision in case an incidental
      carcinoma is found postoperatively on histological study of the specimen. An
      alternative method is unilateral hemithyroidectomy with contralateral subtotal
      resection (the Dunhill procedure). METHOD: Selective literature review. RESULTS:
      Three randomized controlled trials (RCTs) have compared the longterm outcomes of
      different surgical methods. In addition, retrospective studies have been
      published, but their findings must be interpreted with caution because of
      limitations of method. When all of the data are considered, it appears that
      radical procedures are often not justified. According to the RCTs, nodules arose
      during long-term follow-up in 4.7-14% of patients who had undergone subtotal
      resection; yet, in the two more recent and methodologically more valid RCTs,
      surgery for recurrent goiter was needed in only 0-0.5% of patients treated with a
      Dunhill procedure and given adequate hormone supplementation. Most incidental
      carcinomas are papillary microcarcinomas; this entity is usually adequately
      treated with hemithyroidectomy. The reported complication rates of total
      thyroidectomy for permanent hypoparathyroidism in particular range from 0.5% (in
      specialized centers) to 10% (in a cross-sectional study) and thus seem higher
      than the corresponding rate for a Dunhill procedure (1-2%). CONCLUSION: Total
      thyroidectomy has significant risks and should only be performed if the
      indication has been critically assessed. Alternative methods such as the Dunhill
      procedure are often radical enough with a much lower rate of postoperative
      hypoparathyroidism; they remain an important option in thyroid surgery. Further
      RCTs with sufficient long-term follow-up are needed so that the different
      surgical methods can be reliably compared in detail.

PMID- 24666656
TI  - On the frontline of eastern Burma's chronic conflict--listening to the voices of
      local health workers.
AB  - Globally, attacks on and interferences with health workers and healthcare
      delivery, including targeted violence towards providers, attacks on hospitals and
      delays and denial of health care, represent a serious humanitarian and human
      rights issue. However, gaps in research about these events persist, limiting the
      evidence base from which to understand and address the problem. This paper
      focuses on experiences of local health workers in eastern Burma's chronic
      conflict, including their strategies for addressing security and ensuring access
      to vulnerable ethnic communities in the region. Face-to-face in-depth interviews
      were conducted in June and August 2012 with 27 health workers from three health
      organizations that operate throughout eastern Burma, with their operational head
      quarters located in Mae Sot, Tak Province, Thailand. Qualitative analysis found
      that health workers in this setting experience violent and non-violent
      interferences with their work, and that the Burmese government's military
      activities in the region have severely impacted access to care, which remains
      restricted. Data show that innovative security strategies have emerged, including
      the important role of the community in ensuring securer access to health care.
      This study underscores health workers' concern for improved data collection to
      support the rights of health workers to provide health care, and the rights of
      community members to receive health care in conflict-affected settings. Findings
      will inform the development of an incident reporting form to improve systematic
      data collection and documentation of attacks on health in this setting. 

PMID- 24666655
TI  - Allergic sensitization in Canadian chronic rhinosinusitis patients.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is a societal burden and cause of
      morbidity in Canada; however, the prevalence of allergic sensitization in
      Canadian CRS patients has remained poorly characterized. OBJECTIVE: In this
      study, we used skin prick test (SPT) and specific immunoglobulin E (sIgE) and G
      (sIgG) titers to regionally relevant allergen sources in order to determine
      whether allergic sensitization is more prevalent in CRS patients compared to
      chronic idiopathic urticaria (CIU) control patients. METHODS: One hundred and
      fifty eight subjects (19-70 years of age) were recruited into the study. 101
      subjects had a confirmed diagnostic history of CRS and 57 subjects with a
      clinical diagnosis of CIU were recruited as controls. Enrolled subjects underwent
      SPT to a panel of perennial and seasonal allergens and sIgE titers were
      quantified to selected environmental allergen mixes (grass, mold, and tree
      species) using Phadia ImmunoCAP. sIgG was additionally quantified to Alternaria
      alternata, Aspergillus versicolor, Cladosporium herbarum, and Stachybotrys atra.
      Differences between CRS and control CIU patient SPT and serological data were
      examined by chi-squared analysis and analysis of variance. RESULTS: Reactivity to
      at least one SPT extract occurred in 73% of CRS patients. Positive SPT reactivity
      to A. alternata (odds ratio (OR): 4.34, 95% confidence interval: 1.57, 12.02),
      cat (OR: 3.23, 95% CI: 1.16, 9.02), and ragweed (OR: 2.31, 95% CI: 1.02, 5.19)
      extracts were more prevalent in patients with CRS (p < 0.05). Although dust mite
      and timothy grass sensitization approached statistical significance in the chi
      squared analysis of SPT data, other common perennial and seasonal allergens were
      not associated with CRS. No statistically significant differences were observed
      between mean sIgE and sIgG titers in CRS and control patients. CONCLUSIONS: This
      study supports previous data that suggests A. alternata sensitization is
      associated with CRS; however, these findings additionally highlight the
      contribution of other regionally important allergens including cat and ragweed.

PMID- 24666657
TI  - The association between socioeconomic status and disability after stroke:
      findings from the Adherence eValuation After Ischemic stroke Longitudinal (AVAIL)
      registry.
AB  - BACKGROUND: Stroke is the leading cause of disability among adults in the United
      States. The association of patients' pre-event socioeconomic status (SES) with
      post-stroke disability is not well understood. We examined the association of
      three indicators of SES--educational attainment, working status, and perceived
      adequacy of household income--with disability 3-months following an acute
      ischemic stroke. METHODS: We conducted retrospective analyses of a prospective
      cohort of 1965 ischemic stroke patients who survived to 3 months in the Adherence
      eValuation After Ischemic stroke--Longitudinal (AVAIL) study. Multivariable
      logistic regression was used to examine the relationship of level of education,
      pre-stroke work status, and perceived adequacy of household income with
      disability (defined as a modified Rankin Scale of 3-5 indicating activities of
      daily living limitations or constant care required). RESULTS: Overall, 58% of
      AVAIL stroke patients had a high school or less education, 61% were not working,
      and 27% perceived their household income as inadequate prior to their stroke.
      Thirty five percent of patients were disabled at 3-months. After adjusting for
      demographic and clinical factors, stroke survivors who were unemployed or
      homemakers, disabled and not-working, retired, less educated, or reported to have
      inadequate income prior to their stroke had a significantly higher odds of post
      stroke disability. CONCLUSIONS: In this cohort of stroke survivors, socioeconomic
      status was associated with disability following acute ischemic stroke. The
      results may have implications for public health and health service interventions
      targeting stroke survivors at risk of poor outcomes.

PMID- 24666658
TI  - Uterine sutures at prior caesarean section and placenta accreta in subsequent
      pregnancy: a case-control study.
AB  - OBJECTIVE: To clarify the effects of uterine myometrial suture techniques at
      prior caesarean section on the incidence of pathologically diagnosed placenta
      accreta in placenta praevia with prior caesarean section (PPPC). DESIGN: Case
      control study. SETTING: Eleven tertiary referral hospitals in central Japan.
      POPULATION: A total of 98 cases of placenta praevia, a history of one or more
      prior caesarean sections, and a history of uterine transverse incision and usage
      of only absorbable thread for myometrial sutures at the prior caesarean section.
      Exclusions were a history of myomectomy or Strassmann's operation. METHODS: Cases
      were grouped into a pathologically diagnosed placenta accreta group (38 cases)
      and a no accreta group (60 cases). Clinical characteristics including uterine
      suture methods at prior caesarean section were compared (single-layer versus
      double-layer closure; continuous versus interrupted sutures in the inner
      myometrial layer). MAIN OUTCOME MEASURE: The incidence of placenta accreta.
      RESULTS: No difference was found comparing single-layer with double-layer closure
      in the incidence of placenta accreta (37.1 versus 39.7%, P = 0.805); however, a
      significant difference was found comparing continuous with interrupted sutures
      (58.1 versus 29.9%, P = 0.008). Multivariable logistic regression analysis with
      stepwise selection for the eight factors meeting the criterion of P < 0.10 in
      univariate analysis was used, and four independent factors were selected, as
      follows: gravidity >= 3 (adjusted odds ratio, aOR, 3.4, 95% confidence interval,
      95% CI, 0.99-11.6, P = 0.050); total praevia (versus non-total, aOR 18.4, 95% CI
      3.2-107.0, P = 0.001); anterior/centre placenta (versus posterior, aOR 16.4, 95%
      CI 3.7-72.2, P < 0.001); and continuous sutures (versus interrupted, aOR 6.0, 95%
      CI 1.4-25.2, P = 0.015). CONCLUSIONS: In this limited study, a history of
      continuous sutures on the inner side of the uterine wall showed potential to
      influence the development of placenta accreta in PPPC patients.

PMID- 24666659
TI  - Feline eosinophilic dermatoses: a retrospective immunohistochemical and
      ultrastructural study of extracellular matrix remodelling.
AB  - BACKGROUND: Feline eosinophilic dermatoses (FEDs) are common diseases of cats
      with an unknown pathogenesis. They are histologically characterized by an
      eosinophilic infiltration and often by the presence of flame figures (FFs) and/or
      areas of loss of tissue architecture, here termed necrotic foci (NF). It has been
      postulated that an alteration in the degradation of the extracellular matrix
      could be responsible for these histological features. Matrix metalloproteinases
      (MMPs) are a group of proteases that are fundamental in extracellular matrix
      remodelling. HYPOTHESIS/OBJECTIVES: The aim of the study was to investigate
      retrospectively the expression of a subgroup of MMPs, in particular MMP-2 and MMP
      9 gelatinases, in FEDs. The expression of one of their inhibitors, TIMP-2, was
      also investigated in order to establish the role of these molecules in the
      pathogenesis of FEDs. The ultrastructural characteristics of extracellular matrix
      in FFs and NF were subsequently assessed. METHODS: Fifty-one formalin-fixed,
      paraffin-embedded specimens from cutaneous and mucosal biopsies diagnosed as FEDs
      were investigated immunohistochemically. Two selected samples were processed for
      electron microscopy. RESULTS: This study revealed an increased expression of MMP
      2 in NF and a decreased expression of this gelatinase in FFs. An imbalance
      between MMP-2 and TIMP-2 was evident using immunohistochemistry. No significative
      results were observed for MMP-9 expression. Electron microscopy confirmed the
      lack of normal collagen fibres in NF, whereas in FFs only occasional, amorphous
      material was observed among normal collagen fibres. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Our study suggests that an imbalance in the expression of matrix
      metalloproteinases could be responsible for different morphological findings in
      FEDs. Further studies are needed to assess the role of matrix metalloproteinases
      in the pathogenesis of FEDs.

PMID- 24666660
TI  - Fipronil-amitraz-S-methoprene-triggered pemphigus foliaceus in 21 dogs: clinical,
      histological and immunological characteristics.
AB  - BACKGROUND: A recently launched topical ectoparasiticide containing fipronil,
      amitraz and S-methoprene has been associated with the development of an
      acantholytic pustular dermatitis similar to that of Promeris-triggered pemphigus
      foliaceus (PF). HYPOTHESIS/OBJECTIVES: Our objectives were to describe the
      clinical, histological and immunological features of this PF-like cutaneous
      adverse drug reaction. ANIMALS: Twenty-one dogs with a probable or definitive
      diagnosis of PF-like cutaneous adverse drug reaction were identified between May
      2012 and February 2013. MATERIAL AND METHODS: Histology, direct and indirect
      immunofluorescence were employed to address the study objectives. RESULTS: Most
      dogs were middle-aged or older (median, 9 years) and of large size (median, 23
      kg). In six dogs (29%), the PF-like lesions remained confined to the site of
      application, while 15 dogs (71%) exhibited lesions at distant sites. One or two
      applications of the ectoparasiticide were sufficient to trigger PF-like lesions
      in seven (33%) and six (29%) dogs, respectively. Systemic signs were reported in
      nine dogs (43%), all with lesions extending to sites distant from application
      areas. Tissue-bound antikeratinocyte IgG was detected in the lesional epidermis
      of eight of 19 (42%) cases by direct immunofluorescence, while serum
      antikeratinocyte IgG was detected in 10 of 14 (71%) cases by indirect
      immunofluorescence. Autoantibodies were found to target canine desmocollin-1 in
      11 of 14 dogs (79%), but not canine desmoglein-1, by indirect immunofluorescence
      on transfected cells. These immunological findings were similar in cases with
      localized and distant disease. CONCLUSIONS AND CLINICAL IMPORTANCE: This new
      topical ectoparasiticide containing fipronil, amitraz and S-methoprene is capable
      of triggering the development of an acantholytic pustular dermatosis that is a
      clinical, histological and immunological close match for Promeris-triggered PF
      and naturally occurring autoimmune PF in dogs.

PMID- 24666661
TI  - Clinical and histological characterization of multifocal, spontaneous,
      noninfectious alopecia in Norwegian puffin dogs (lundehunds).
AB  - BACKGROUND: A noninfectious, spontaneous, multifocal alopecia has been recognized
      in Norwegian puffin dogs. HYPOTHESIS/OBJECTIVES: This study aimed to report
      demographic information, history, clinical signs, histopathological features and
      follow-up information for alopecic Norwegian puffin dogs from Sweden. MATERIAL
      AND METHODS: A questionnaire was sent out to all members of the breed
      association. Dogs clinically diagnosed with alopecia and biopsied were allocated
      to Group A. Dogs reported with alopecia for which histopathology was not
      available were allocated to Group B. RESULTS: Group A included 14 dogs (11.7% of
      the breed population in Sweden). Information regarding 72 dogs (60% of the breed
      population) was collected via questionnaire, and alopecia without histopathology
      was reported in another five dogs (Group B). Gender distribution was equal.
      Median age of onset was 1.5 years (range 8 months to 7 years). Multifocal or
      serpiginous alopecia, follicular plugging, dry skin, slight scaling and pruritus
      were characteristic. Extensive, widespread alopecia was not seen, and lesions
      were recorded only in haired skin. A lymphoplasmacytic, mural, isthmus
      folliculitis/perifolliculitis with follicular and perifollicular mucin was
      observed. Inflammation did not involve the hair bulb; atrophy was sometimes
      present. The inflammation sometimes extended to sebaceous glands, resulting in
      atrophy and absence of glands. Follow-up ranged from 6 months to 12 years (mean
      3.2 years). Spontaneous remission was rare. Estrus was associated with worsening
      of the disease or relapse. Oral prednisolone reduced pruritus but was not
      effective in resolving clinical lesions. All dogs treated with ciclosporin went
      into remission. CONCLUSIONS AND CLINICAL IMPORTANCE: This is the first report of
      mural, mucinotic, isthmus folliculitis alopecia in Norwegian puffin dogs.

PMID- 24666662
TI  - mecC- and mecA-positive meticillin-resistant Staphylococcus aureus (MRSA)
      isolated from livestock sharing habitat with wildlife previously tested positive
      for mecC-positive MRSA.

PMID- 24666663
TI  - Cognitive function, body mass index and mortality in a rural elderly Chinese
      cohort.
AB  - BACKGROUND: Previous studies have shown that poor cognition and low body mass
      index were associated with increased mortality. But few studies have investigated
      the association between cognition and mortality across the entire cognitive
      spectrum while adjusting for BMI. The objective of this study is to examine the
      associations between cognitive function, BMI and 7-year mortality in a rural
      elderly Chinese cohort. METHODS: A prospective cohort of 2,000 Chinese age 65 and
      over from four rural counties in China were followed for 7-years. Cognitive
      function, BMI and other covariate information were obtained at baseline. Cox's
      proportional hazard models were used to determine the effects of cognitive
      function and BMI on mortality risk. RESULTS: Of participants enrolled, 473
      (23.7%) died during follow-up. Both lower cognitive function (HR = 1.48, p =
      0.0049) and lower BMI (HR = 1.6, p < 0.0001) were independently associated with
      increased mortality risk compared to individuals with average cognitive function
      and normal weight. Higher cognitive function was associated with lower mortality
      risk (HR = 0.69, p = 0.0312). We found no significant difference in mortality
      risk between overweight/obese participants and those with normal weight.
      CONCLUSIONS: Cognitive function and BMI were independent predictors of mortality
      risk. Intervention strategies for increasing cognitive function and maintaining
      adequate BMI may be important in reducing morality risk in the elderly
      population.

PMID- 24666664
TI  - Aberrant drug-related behavior observed during a 12-week open-label extension
      period of a study involving patients taking chronic opioid therapy for persistent
      pain and fentanyl buccal tablet or traditional short-acting opioid for
      breakthrough pain.
AB  - OBJECTIVE: Evaluate aberrant drug-related behaviors in patients administering
      fentanyl buccal tablet or traditional short-acting opioids for breakthrough pain.
      DESIGN: Twelve-week open-label extension. SETTING: Forty-two US sites. SUBJECTS:
      Opioid-tolerant patients with chronic pain who completed the previous randomized,
      double-blind, crossover portion of a study comparing fentanyl buccal tablet and
      immediate-release oxycodone for treatment of breakthrough pain. METHODS: Patients
      were rerandomized to continue treatment with fentanyl buccal tablet or begin any
      traditional short-acting opioid. Assessments included Screener and Opioid
      Assessment for Patients with Pain-Revised (SOAPP-R) at baseline and Addiction
      Behaviors Checklist and Current Opioid Misuse Measure at baseline and final
      visit. Case report forms were reviewed retrospectively to identify aberrant drug
      related behaviors. RESULTS: One hundred thirty patients entered the open-label
      extension (fentanyl buccal tablet, N = 65; traditional short-acting opioid, N =
      65). SOAPP-R scores were <18 (low risk of aberrant drug-related behavior) in 74%
      of patients; no significant differences in SOAPP-R scores were observed between
      treatment groups. At the final visit, <=14% of patients in each treatment group
      had scores indicating potential aberrant drug-related behavior (Addiction
      Behaviors Checklist >=3, Current Opioid Misuse Measure >=9); no significant
      differences in scores were observed between treatment groups. Baseline SOAPP-R
      score >=18 was not predictive of Addiction Behaviors Checklist >=3 but was
      predictive of Current Opioid Misuse Measure >=9. Aberrant behaviors were
      identified in 12 (18%) fentanyl buccal tablet patients and 13 (20%) traditional
      short-acting opioid patients. CONCLUSIONS: Incidence of aberrant drug-related
      behaviors was similar between patients taking fentanyl buccal tablet and
      traditional short-acting opioids over 12 weeks.

PMID- 24666665
TI  - Comparison of the long-term effects of high-fat v. low-fat diet consumption on
      cardiometabolic risk factors in subjects with abnormal glucose metabolism: a
      systematic review and meta-analysis.
AB  - The aim of the present systematic review and meta-analysis was to examine the
      long-term effects (>= 12 months) of high-fat (HF) v. low-fat (LF) diet
      consumption on the indicators of glycaemic control as well as cardiovascular risk
      factors in pre-diabetic and diabetic individuals. Literature search was carried
      out using the electronic databases MEDLINE, Embase and the Cochrane Trial
      Register until November 2013. Study-specific weighted mean differences (MD) were
      pooled using a random-effects model of the Cochrane software package Review
      Manager 5.1 and Stata 12.0 was used for meta-regressions. A total of fourteen
      trials met the inclusion criteria and a maximum of 1753 subjects were included in
      the meta-analysis. HF regimens were found to result in a significant decrease in
      TAG levels (MD -0.19 mmol/l, 95 % CI -0.23, -0.14, P< 0.001; I2 = 0 %, P= 0.58)
      and diastolic blood pressure (MD -1.30 mmHg, 95 % CI -1.73, -0.87, P< 0.001; I2 =
      0 %, P= 0.60) and a significant increase in HDL-cholesterol levels (MD 0.05
      mmol/l, 95 % CI 0.01, 0.08, P= 0.01; I2 = 57 %, P= 0.01). In addition, MD in the
      reductions of fasting glucose levels (-0.41 mmol/l, 95 % CI -0.74, -0.08, P=
      0.01; I2 = 56 %, P= 0.02) were significantly high in patients with type 2
      diabetes adhering to a HF diet. HF and LF diets might not be of equal value in
      the management of either pre-diabetes or type 2 diabetes, leading to emphasis
      being placed on the recommendations of HF diets.

PMID- 24666666
TI  - A complete response to mFOLFOX6 and panitumumab chemotherapy in advanced stage
      rectal adenocarcinoma: a case report.
AB  - BACKGROUND: Pathological complete remission of advanced stage rectal
      adenocarcinoma by chemotherapy alone is rare. A case of advanced stage, low-lying
      rectal adenocarcinoma in which a complete response to treatment was obtained with
      mFOLFOX6 and panitumumab (Pmab) is reported. CASE PRESENTATION: A 53-year-old man
      was referred to Shiga University of Medical Science hospital Shiga, Japan,
      complaining of bloody stool. Gastrointestinal endoscopy was performed, and
      advanced stage rectal adenocarcinoma was diagnosed. Computed tomography (CT)
      revealed regional lymph node metastases in the mesorectum. Neoadjuvant
      chemotherapy (NAC) with mFOLFOX6 and Pmab was planned.Endoscopy following four
      courses of chemotherapy revealed that the rectal cancer had been markedly
      reduced, and the results of biopsies of the rectal tumor were negative for
      cancer. On CT, the mesorectal lymph node metastases had disappeared. Total
      intersphincteric resection (ISR) with a handsewn coloanal anastomosis was
      performed. Histological examination showed a complete response to mFOLFOX6 and
      Pmab in advanced stage rectal cancer. CONCLUSION: The result seen in this case
      suggests that short-term NAC with mFOLFOX6 and Pmab was effective for low-lying
      rectal adenocarcinoma.

PMID- 24666667
TI  - PerCEN: a cluster randomized controlled trial of person-centered residential care
      and environment for people with dementia.
AB  - BACKGROUND: There is good evidence of the positive effects of person-centered
      care (PCC) on agitation in dementia. We hypothesized that a person-centered
      environment (PCE) would achieve similar outcomes by focusing on positive
      environmental stimuli, and that there would be enhanced outcomes by combining PCC
      and PCE. METHODS: 38 Australian residential aged care homes with scope for
      improvement in both PCC and PCE were stratified, then randomized to one of four
      intervention groups: (1) PCC; (2) PCE; (3) PCC +PCE; (4) no intervention. People
      with dementia, over 60 years of age and consented were eligible. Co-outcomes
      assessed pre and four months post-intervention and at 8 months follow-up were
      resident agitation, emotional responses in care, quality of life and depression,
      and care interaction quality. RESULTS: From 38 homes randomized, 601 people with
      dementia were recruited. At follow-up the mean change for quality of life and
      agitation was significantly different for PCE (p = 0.02, p = 0.05, respectively)
      and PCC (p = 0.0003, p = 0.002 respectively), compared with the non-intervention
      group (p = 0.48, p = 0.93 respectively). Quality of life improved non
      significantly for PCC+PCE (p = 0.08), but not for agitation (p = 0.37).
      Improvements in care interaction quality (p = 0.006) and in emotional responses
      to care (p = 0.01) in PCC+PCE were not observed in the other groups. Depression
      scores did not change in any of the groups. Intervention compliance for PCC was
      59%, for PCE 54% and for PCC+PCE 66%. CONCLUSION: The hypothesis that PCC+PCE
      would improve quality of life and agitation even further was not supported, even
      though there were improvements in the quality of care interactions and resident
      emotional responses to care for some of this group. The Australian New Zealand
      Clinical Trials Registry Number is ACTRN 12608000095369.

PMID- 24666669
TI  - Minimally invasive lateral lumbar interbody fusion with direct psoas
      visualization.
AB  - BACKGROUND: Minimally invasive lateral approaches to the lumbar spine have been
      adopted to allow access to the intervertebral disc space while avoiding the
      complications associated with anterior or posterior approaches. This report
      describes a minimally invasive technique for lateral lumbar interbody fusion LLIF
      that allows direct intraoperative visualization of the psoas and surrounding
      neurovasculature (DV-LIF). METHODS: The technique utilizes a radiolucent tubular
      retractor and a secondary psoas retractor that allows a muscle-sparing approach
      while offering excellent visualization of the operative site. The unique
      advantage of this procedure is that the psoas muscle and surrounding nerves can
      be directly visualized intraoperatively to supplement neuromonitoring. We
      retrospectively reviewed complication rates in 34 patients treated with DV-LLIF
      (n = 19) or standard lateral lumbar interbody fusion (S-LLIF, n = 15). RESULTS:
      There were 29 complications (median: 1 per patient) with DV-LLIF and 20 (median:
      1 per patient) complications with S-LLIF. Postoperative sensory deficits were
      reported in eight (42%) and seven (47%) patients, respectively. Thigh pain or
      numbness was reported in eight (42%) and five (33%) patients, respectively. The
      percentage of the overall complications directly attributable to the procedure
      was 69% with DV-LLIF and 83% with S-LLIF. One severe complication (back pain) was
      reported in one DV-LLIF patient and four severe complications (severe bleeding,
      respiratory failure, deep venous thrombosis and gastrointestinal prophylaxis, and
      nicked renal vein and aborted procedure) were reported in two S-LLIF patients.
      CONCLUSIONS: Preliminary evidence suggests that minimally invasive lateral
      interbody fusion with direct psoas visualization may reduce the risk for severe
      procedural complications.

PMID- 24666668
TI  - Genome-wide association study for intramuscular fat deposition and composition in
      Nellore cattle.
AB  - BACKGROUND: Meat from Bos taurus and Bos indicus breeds are an important source
      of nutrients for humans and intramuscular fat (IMF) influences its flavor,
      nutritional value and impacts human health. Human consumption of fat that
      contains high levels of monounsaturated fatty acids (MUFA) can reduce the
      concentration of undesirable cholesterol (LDL) in circulating blood. Different
      feeding practices and genetic variation within and between breeds influences the
      amount of IMF and fatty acid (FA) composition in meat. However, it is difficult
      and costly to determine fatty acid composition, which has precluded beef cattle
      breeding programs from selecting for a healthier fatty acid profile. In this
      study, we employed a high-density single nucleotide polymorphism (SNP) chip to
      genotype 386 Nellore steers, a Bos indicus breed and, a Bayesian approach to
      identify genomic regions and putative candidate genes that could be involved with
      deposition and composition of IMF. RESULTS: Twenty-three genomic regions (1-Mb
      SNP windows) associated with IMF deposition and FA composition that each explain
      >=1% of the genetic variance were identified on chromosomes 2, 3, 6, 7, 8, 9, 10,
      11, 12, 17, 26 and 27. Many of these regions were not previously detected in
      other breeds. The genes present in these regions were identified and some can
      help explain the genetic basis of deposition and composition of fat in cattle.
      CONCLUSIONS: The genomic regions and genes identified contribute to a better
      understanding of the genetic control of fatty acid deposition and can lead to DNA
      based selection strategies to improve meat quality for human consumption.

PMID- 24666670
TI  - Expression of three Trichoderma reesei cellulase genes in Saccharomyces
      pastorianus for the development of a two-step process of hydrolysis and
      fermentation of cellulose.
AB  - AIMS: To compare the production of recombinant cellulase enzymes in two
      Saccharomyces species so as to ascertain the most suitable heterologous host for
      the degradation of cellulose-based biomass and its conversion into bioethanol.
      METHOD AND RESULTS: cDNA copies of genes representing the three major classes of
      cellulases (Endoglucanases, Cellobiohydrolases and beta-glucosidases) from
      Trichoderma reesei were expressed in Saccharomyces pastorianus and Saccharomyces
      cerevisiae. The recombinant enzymes were secreted by the yeast hosts into the
      medium and were shown to act in synergy to hydrolyse cellulose. The conditions
      required to achieve maximum release of glucose from cellulose by the recombinant
      enzymes were defined and the activity of the recombinant enzymes was compared to
      a commercial cocktail of T. reesei cellulases. CONCLUSIONS: We demonstrate that
      significantly higher levels of cellulase activity were achieved by expression of
      the genes in S. pastorianus compared to S. cerevisiae. Hydrolysis of cellulose by
      the combined activity of the recombinant enzymes was significantly better at 50
      degrees C than at 30 degrees C, the temperature used for mesophilic yeast
      fermentations, reflecting the known temperature profiles of the native enzymes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results demonstrate that host choice is
      important for the heterologous production of cellulases. On the basis of the low
      activity of the T. reesei recombinant enzymes at fermentation temperatures, we
      propose a two-step process for the hydrolysis of cellulose and its fermentation
      into alcohol using cellulases produced in situ.

PMID- 24666672
TI  - The roles of traditional Chinese medicine in gene therapy.
AB  - The field of gene therapy has been increasingly studied in the last four decades,
      and its clinical application has become a reality in the last 15 years.
      Traditional Chinese medicine (TCM), an important component of complementary and
      alternative medicine, has evolved over thousands of years with its own unique
      system of theories, diagnostics and therapies. TCM is well-known for its various
      roles in preventing and treating infectious and chronic diseases, and its usage
      in other modern clinical practice. However, whether TCM can be applied alongside
      gene therapy is a topic that has not been systematically examined. Here we
      provide an overview of TCM theories in relation to gene therapy. We believe that
      TCM theories are congruent with some principles of gene therapy. TCM-derived
      drugs may also act as gene therapy vehicles, therapeutic genes, synergistic
      therapeutic treatments, and as co-administrated drugs to reduce side effects. We
      also discuss in this review some possible approaches to combine TCM and gene
      therapy. 

PMID- 24666673
TI  - Natural modulators of liver X receptors.
AB  - Nuclear receptor transcription factors are ligand-activated proteins that control
      various biological events from cell growth and development to lipid metabolism,
      and energy and glucose homeostasis. Nuclear receptors are important drug targets
      for metabolic diseases. Liver X receptors (LXRs) are nuclear receptor
      transcription factors that play essential roles in regulation of cholesterol,
      triglyceride, fatty acid, and glucose homeostasis. LXR-deficient mice have shown
      the association of LXR-signaling pathway dysfunction with several human
      pathologies including atherosclerosis, hyperlipidemia, Alzheimer's disease and
      cancer. Thus, LXRs are promising pharmacological targets for these diseases.
      Synthetic LXR agonists may lower cholesterol, but increase triglyceride and
      induce fatty liver. The naturally occurring LXR ligands, with moderate activity,
      may serve as nutraceuticals for prevention or treatment of the disorders, while
      minimizing potential side effects. In this review, recent advances in natural LXR
      modulators are summarized including agonist, antagonist and the modulator of LXR
      pathway. 

PMID- 24666674
TI  - Pharmacological effects and active phytoconstituents of Swietenia mahagoni: a
      review.
AB  - The usage of Swietenia mahagoni, a popular medicinal plant in India and some
      African countries, dates back to ancient times for its curative properties in
      diseases like malaria, diabetes, and diarrhea. It is also used as an anti
      pyretic, bitter tonic and astringent. Its pharmacological activities are being
      widely explored. Although many important groups of phytochemicals have been
      identified and isolated from various parts of the plant, most of these researches
      have been focused on seeds. Toxicological studies have established the safety of
      many of these plant extracts, and found insignificant side effects. Here we
      present a comprehensive review of all the pharmacological effects and constituent
      phytochemicals of the plant. 

PMID- 24666671
TI  - Modular organization of cardiac energy metabolism: energy conversion, transfer
      and feedback regulation.
AB  - To meet high cellular demands, the energy metabolism of cardiac muscles is
      organized by precise and coordinated functioning of intracellular energetic units
      (ICEUs). ICEUs represent structural and functional modules integrating multiple
      fluxes at sites of ATP generation in mitochondria and ATP utilization by
      myofibrillar, sarcoplasmic reticulum and sarcolemma ion-pump ATPases. The role of
      ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and
      fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to
      adjust to intracellular energy needs through the dynamic system of
      compartmentalized phosphoryl transfer networks. One of the key elements in
      regulation of energy flux distribution and feedback communication is the
      selective permeability of mitochondrial outer membrane (MOM) which represents a
      bottleneck in adenine nucleotide and other energy metabolite transfer and
      microcompartmentalization. Based on the experimental and theoretical
      (mathematical modelling) arguments, we describe regulation of mitochondrial ATP
      synthesis within ICEUs allowing heart workload to be linearly correlated with
      oxygen consumption ensuring conditions of metabolic stability, signal
      communication and synchronization. Particular attention was paid to the structure
      function relationship in the development of ICEU, and the role of mitochondria
      interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM
      permeability in response to energy metabolic signals providing regulation of
      mitochondrial respiration. Emphasis was given to the importance of creatine
      metabolism for the cardiac energy homoeostasis. 

PMID- 24666675
TI  - Hand self-Shiatsu for sleep problems in persons with chronic pain: a pilot study.
AB  - OBJECTIVE: Difficulty falling asleep (sleep latency) and staying asleep (sleep
      maintenance) are common problems for persons living with pain. Research
      demonstrates that sleep problems are, in turn, related to exacerbation of chronic
      pain. There is a growing body of evidence for a range of pragmatic, non
      pharmacological sleep interventions that can potentially be incorporated into
      pain management programs. This study looks at the outcome of teaching patients
      with musculoskeletal pain standardized pre-bedtime hand self-Shiatsu (HSS) to
      reduce sleep latency. METHODS: A case series design, with participants acting as
      their own controls, was selected to facilitate hypothesis generation for this
      novel, under-researched intervention. Sleep efficiency, latency and maintenance,
      sleep beliefs, pain intensity and basic participant demographics were collected
      at baseline with actigraphy and standardized self-report questionnaires. After
      one week of baseline data collection, the HSS intervention was taught to
      participants. Follow-up data were collected at 2 and 8 weeks post-intervention.
      RESULTS: Data collected at baseline and the two follow-up periods revealed no
      apparent changes in the objective actigraphy data. However a trend toward
      improved self-reported sleep latency (time to fall asleep) and sleep duration
      (time spent asleep) emerged. A number of participants reported they were more
      concerned with increasing their period of unbroken sleep as opposed to their
      total sleep time and it is possible that HSS may be useful to be applied during
      nighttime awakenings as well as before bed. None of the participants reported
      adverse effects of the intervention. CONCLUSION: These preliminary findings are
      promising and future studies exploring the mechanism of action and with stronger
      control of treatment fidelity are indicated.

PMID- 24666676
TI  - Oleanolic acid isolated from ethanolic extract of Phytolacca decandra induces
      apoptosis in A375 skin melanoma cells: drug-DNA interaction and signaling
      cascade.
AB  - OBJECTIVE: Oleanolic acid (OA) has been reported to have anticancer effects, but
      the extent of its cytotoxicity, its ability to interact with nuclear DNA, its
      action against skin melanoma, as well as the molecular mechanism of its action
      against cell proliferation and in support of cell death are still unexplored.
      This led us to examine the efficacy of OA, a bioactive compound isolated from
      Phytolacca decandra, on these issues in the present investigation. METHODS:
      Studies related to analyses of cell viability, drug-DNA interaction, cell
      proliferation, cell cycle and epidermal growth factor receptor (EGFR) activity
      were performed. To investigate whether cells undergo apoptosis, studies like
      fluorescence microscopy, poly (ADP-ribose) polymerase (PARP) degradation, annexin
      V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial
      membrane potential and activity of some relevant signaling proteins were
      performed. RESULTS: OA displayed a minimal and negligible cytotoxic effect on
      normal HaCaT cells (skin keratinocytes) and peripheral blood mononuclear cells
      but by contrast it reduced A375 cell viability significantly. OA interacted with
      nuclear DNA quickly after exposure. It acted as an anti-proliferative agent. It
      suppressed EGFR activity. OA administration led the cells to mitochondria
      dependent caspase 3-mediated apoptosis. CONCLUSION: OA interacts with cellular
      DNA, inhibits proliferation possibly through modulating EGFR activity and induces
      mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would
      qualify it as a potent anticancer agent.

PMID- 24666678
TI  - Medicinal potential of Passiflora foetida L. plant extracts: biological and
      pharmacological activities.
AB  - OBJECTIVE: To investigate analgesic, antidiarrhoeal and cytotoxic activities of
      the ethanol extract of Passiflora foetida L. (Passifloraceae) by three
      experimental methods. METHODS: Analgesic activity of the ethanol extract of
      Passiflora foetida L. (EEPF) acetic acid-induced writhing inhibition in mice. The
      method of castor oil-induced diarrhoea in mice was utilized to evaluate
      antidiarrhoeal activity. The cytotoxic activity of EEPF was explored with a brine
      shrimp lethality bioassay. RESULTS: The extract showed 68.75% and 30.00%
      inhibition of writhe at the doses of 500 and 250 mg/kg body weight, respectively.
      The extract increased the mean latent period prior to diarrhoeal onset to about
      1.55 h and 1.17 h, and decreased the mean number of stools to 4.4 and 5.6 at the
      doses of 500 and 250 mg/kg body weight. The extract also demonstrated cytotoxic
      activity in the brine shrimp lethality assay, and the median lethal concentration
      for brine shrimp nauplii was 80 MUg/mL. CONCLUSION: The results suggest that the
      plant extract has analgesic and antidiarrhoeal activities, supporting its uses in
      traditional medicine. The results also demonstrate that the plant extract
      possesses cytotoxic activities.

PMID- 24666677
TI  - Protective effect of ginger volatile oil against acetic acid-induced colitis in
      rats: a light microscopic evaluation.
AB  - OBJECTIVE: Ulcerative colitis is a chronically recurrent inflammatory bowel
      disease of unknown origin. In the present study, the effect of ginger (rhizome of
      Zingiber officinale Roscoe) volatile oil on a rat model of colitis was evaluated.
      METHODS: Volatile oil of ginger with doses of 100, 200, and 400 mg/kg,
      prednisolone (4 mg/kg), or vehicle were administered orally to groups of male
      Wistar rats (n = 6) for 5 d. Animals were randomly divided into 6 groups, each
      group consisting of 6 rats. Colitis was induced by intracolonic instillation of 2
      mL of 4% (v/v) acetic acid solution. All rats were sacrificed 24 h later and the
      tissue injuries were assessed macroscopically and histopathologically. RESULTS:
      Ginger volatile oil with all doses reduced colon weight/length ratio (P < 0.01)
      and the effects were similar to the reference drugs. Higher oral doses of
      volatile oil (200 and 400 mg/kg) reduced ulcer severity (P < 0.05 and P < 0.01),
      ulcer area (P < 0.01) and ulcer index (P < 0.01). On the other hand, evaluation
      of microscopic scores showed that the dose of 400 mg/kg of volatile oil was
      effective to reduce inflammation severity (P < 0.01) and inflammation extent (P <
      0.05) compared to the control group. CONCLUSION: It is concluded that ginger
      volatile oil could effectively reduce symptoms of experimental colitis in a dose
      dependent manner.

PMID- 24666679
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      Diseases of Gynecology and Obstetrics (Part 1).

PMID- 24666680
TI  - A descriptive study on complementary and alternative medicine use in 0 to 1-year
      old infants and nurses' awareness and recommendation for complementary and
      alternative medicine.
AB  - This study aimed to determine complementary and alternative medicine (CAM)
      recommended by midwives and nurses and used by mothers on their 0 to 1-year-old
      infants. A cross-sectional survey design was used. The sample of the study
      consisted of 65 midwives and mothers of 349 infants registered at these health
      care centres. The frequency of CAM use on a regular basis by mothers
      participating in the study on their infants was 24.6%, whereas the frequency of
      CAM use for a while was 41.3%. Of the mothers using CAM, 81.5-98.5% stated that
      the method they were employing was useful. The mothers used CAM on their infants,
      and the midwives and nurses recommended CAM use. However, the midwives and nurses
      themselves should be first trained to be able to inform individuals/mothers about
      CAM. Evidence-based studies on CAM are needed. 

PMID- 24666681
TI  - Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells
      for T cell proliferation and cytokine response.
AB  - BACKGROUND: Tissue-resident antigen-presenting cells (APC) exert a major
      influence on the local immune environment. Microglia are resident myeloid cells
      in the central nervous system (CNS), deriving from early post-embryonic
      precursors, distinct from adult hematopoietic lineages. Dendritic cells (DC) and
      macrophages infiltrate the CNS during experimental autoimmune encephalomyelitis
      (EAE). Microglia are not considered to be as effective APC as DC or macrophages.
      METHODS: In this work we compared the antigen presenting capacity of CD11c+ and
      CD11c- microglia subsets with infiltrating CD11c+ APC, which include DC. The
      microglial subpopulations (CD11c- CD45dim CD11b+ and CD11c+ CD45dim CD11b+) as
      well as infiltrating CD11c+ CD45high cells were sorted from CNS of C57BL/6 mice
      with EAE. Sorted cells were characterised by flow cytometry for surface phenotype
      and by quantitative real-time PCR for cytokine expression. They were co-cultured
      with primed T cells to measure induction of T cell proliferation and cytokine
      response. RESULTS: The number of CD11c+ microglia cells increased dramatically in
      EAE. They expressed equivalent levels of major histocompatibility complex and co
      stimulatory ligands CD80 and CD86 as those expressed by CD11c+ cells infiltrating
      from blood. CD11c+ microglia differed significantly from blood-derived CD11c+
      cells in their cytokine profile, expressing no detectable IL-6, IL-12 or IL-23,
      and low levels of IL-1beta. By contrast, CD11c- microglia expressed low but
      detectable levels of all these cytokines. Transforming growth factor beta
      expression was similar in all three populations. Although CNS-resident and blood
      derived CD11c+ cells showed equivalent ability to induce proliferation of myelin
      oligodendrocyte glycoprotein-immunised CD4+ T cells, CD11c+ microglia induced
      lower levels of T helper (Th)1 and Th17 cytokines, and did not induce Th2
      cytokines. CONCLUSIONS: Our findings show distinct subtypes of APC in the
      inflamed CNS, with a hierarchy of functional competence for induction of CD4+ T
      cell responses.

PMID- 24666682
TI  - Asthma incidence and risk factors in a national longitudinal sample of adolescent
      Canadians: a prospective cohort study.
AB  - BACKGROUND: Estimates of asthma incidence and its possible determinants in
      adolescent populations have rarely been obtained using prospective designs. We
      sought to identify socio-demographic and other patterns in the incidence of
      asthma among Canadian adolescents and to examine possible behavioural and
      environmental determinants of asthma incidence using longitudinal analyses.
      METHODS: We used data from the National Population Health Survey (NPHS), a
      nationally representative longitudinal survey of Canadians. All persons aged 12
      18 years without asthma at baseline were followed up to a maximum of 12 years.
      The outcome was a reported diagnosis of asthma during the follow-up period.
      Analyses were weighted to the population and bootstrapping procedures were used
      to estimate variances. RESULTS: Participants (n = 956) represented 2,038,890
      adolescents of whom 293,450 (14.4%) developed asthma over the 21,274,890 person
      years of follow-up. Overall, the incidence of asthma was 10.2 per 1000 person
      years. In adjusted Cox regression analysis, being female (HR = 2.13, 95% CI =
      1.26-3.62, p = 0.005) and being exposed to passive smoking (HR = 2.06, 95% CI =
      1.27-3.34, p = 0.003) were associated with the development of asthma while no
      statistically significant associations were identified for rural residence, being
      overweight, and other health behaviours. There was also an apparent cohort effect
      among girls where girls who were older at baseline reported being diagnosed with
      asthma more over the follow-up than their younger counterparts. This was not
      observed among males. CONCLUSIONS: Asthma prevention initiatives for adolescents
      should target girls and focus on smoking exposures. The role that differential
      diagnostic patterns play in these observations should be investigated to more
      accurately assess the incidence of asthma.

PMID- 24666683
TI  - Endoscopically assisted removal of a fish bone penetrating the parotid duct: an
      unusual case.
AB  - PURPOSE: The aim was to evaluate the efficacy of endoscopy-assisted surgery for
      treating a foreign body (fish bone) deeply embedded in the parotid duct. PATIENTS
      AND METHODS: We report the case of a 67-year-old man with diffuse swelling of the
      cheek and the discharge of pus from the parotid duct orifice caused by a fish
      bone that had penetrated into the parotid duct. The preoperative examination
      using ultrasonography and computed tomography showed a linear foreign body.
      RESULTS: The fish bone was thought to be embedded deeply in the parotid duct;
      therefore, we used a combined approach (endoscopy with open surgery), because we
      anticipated difficulties with endoscopic removal of the fish bone. The endoscopic
      view showed that the fish bone had partially penetrated the soft tissue in the
      parotid duct wall, but the fish bone could not be removed endoscopically. With
      endoscopic assistance, the impacted fish bone was removed using an intraoral
      surgical approach. The clinical outcome was satisfactory during a 10-month follow
      up period, with no evidence of complications. CONCLUSIONS: The combined surgical
      and endoscopic approach resulted in the safe and effective removal of a foreign
      body from the salivary duct that could not be removed using sialendoscopy alone.

PMID- 24666684
TI  - Marked, transient, emotion-triggered QT accentuation in an adolescent female with
      type 1 long QT syndrome.
AB  - Type 1 long QT syndrome is the most common long QT syndrome genetic subtype.
      Exercise and emotional stress can precipitate sudden cardiac events in patients
      with type 1 long QT syndrome; however, the precise mechanism remains elusive. We
      report the case of a teenage girl with type 1 long QT syndrome secondary to a
      rare frameshift mutation (p. L191fs+90X) in the KCNQ1-encoded Kv7.1 potassium
      channel. During emotional distress, her continuous QTc recordings precipitously
      increased, peaking within minutes to 669 ms and then returning to baseline (520
      ms) as she calmed without concomitant increase in heart rate. This is the first
      described case documenting transient, marked accentuation of the QTc interval in
      a long QT syndrome patient during emotional distress. Such events may be
      triggered by transient accentuation of the intrinsic perturbation in cardiac
      repolarisation and increase the risk of degeneration to a ventricular arrhythmia.
      This case illustrates the need improved understanding of the complex interaction
      between emotion and cardiac stability in patients with long QT syndrome. 

PMID- 24666685
TI  - Serum AMH level as a marker of acute and long-term effects of chemotherapy on the
      ovarian follicular content: a systematic review.
AB  - Anti-Mullerian hormone (AMH) is a very sensitive indicator of the ovarian
      follicular content. Chemotherapeutic agents are notoriously ovariotoxic in that
      they damage follicles. The aim of this systematic review was to investigate the
      interest of serum AMH variations in determining the acute and long-term effects
      of chemotherapy on the ovarian reserve. According to the PRISMA guidelines,
      searches were conducted on PubMed for all English language articles until
      December 2013. Fifteen articles that focused on dynamic variations of AMH levels
      before and after chemotherapy were selected. Cancer patients have significantly
      lower AMH after chemotherapy than age-matched controls. Longitudinal studies of
      AMH variations before, during and after chemotherapy provide information about
      the degree of follicle loss for each patient according to different chemotherapy
      regimens. Different patterns of AMH levels during the ovarian recovery phase make
      it possible to discriminate between high and low gonadotoxic chemotherapy
      protocols. In addition, pretreatment AMH levels are shown to predict the long
      term ovarian function after the end of treatment. These results may help to
      better understand the ovarian toxicity mechanisms of chemotherapy and to predict
      the degree of the ovarian follicle loss. Therefore, it can be useful for
      fertility preservation strategies, fertility counseling and future family
      planning. 

PMID- 24666687
TI  - Six-month prospective study of fall risk factors identification in patients post
      stroke.
AB  - AIM: To determine if the findings at month 1 could correctly identify stroke
      patients who fell in the 6 months post-stroke; and to describe the
      characteristics of fallers and non-fallers, and their courses of recovery.
      METHODS: Of 133 volunteers who had their first stroke, 98 participants completed
      the assessment three times. Fall incidence and history were collected by
      telephone every 2 weeks and recorded. Fear of falling measured by the Fall
      Efficacy Scale (FES-S), the amount of time that physical therapy was received,
      and standardized outcome measures according to the International Classification
      Functioning, Disability and Health model were measured at month 1, 3 and 6 after
      stroke. The Berg Balance Scale, Barthel Index, Timed Up & Go, 10-m (10mWT) and 2
      min walks and participation subscore of Stroke Impact Scale were used for
      assessment. RESULTS: A total of 25 patients (25%) fell in the 6 months; 13 had
      multiple falls. Fallers showed less improvement in impairments, activity and
      community participation compared with non-fallers. The risk of falling was
      greater than 1 (odds ratio [OR]) when assessed by all outcome measures at month
      1, and was double at month 3. The FES-S >= 33 at month 1 could accurately
      identify a faller (OR 2.99, 95% confidence interval 1.07-8.37), moderate to high
      sensitivity (76%), specificity (49%), and positive and negative predicted value
      (34% and 85%). CONCLUSIONS: Fear of falling was the best indicator of falling.
      Receiving physical therapy after a stroke seems to highly contribute to improved
      functional independence of activities in daily living, and increased self
      confidence and cognitive function.

PMID- 24666686
TI  - The pharmacokinetics of methadone and its metabolites in neonates, infants, and
      children.
AB  - BACKGROUND: The lack of methadone pharmacokinetic data in children and neonates
      restrains dosing to achieve the target concentration in these populations. A
      minimum effective analgesic concentration of methadone in opioid naive adults is
      0.058 mg.l(-1) , while no withdrawal symptoms were observed in neonates suffering
      opioid withdrawal if plasma concentrations of methadone were above 0.06 mg.l(-1)
      . The racemate of methadone which is commonly used in pediatric and anesthetic
      care is metabolized to 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)
      and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP). METHODS: Data from four
      studies (age 33-week PMA-15 years) were pooled (n = 56) for compartment analysis
      using nonlinear mixed effects modeling. Parameter estimates were standardized to
      a 70-kg person using an allometric model approach. Investigation was made of the
      racemate and metabolite (EDDP and EMDP) dispositions. In addition, neonatal data
      (n = 7) allowed further study of R- and S-enantiomer pharmacokinetics. RESULTS: A
      three-compartment linear disposition model best described the observed time
      concentration profiles with additional compartments for metabolites. Population
      parameter estimates (between-subject variability) were central volume (V1) 21.5
      (29%) l.70 kg(-1) , peripheral volumes of distribution V2 75.1 (23%) l.70 kg(-1)
      and V3 484 (8%) l.70 kg(-1) , clearance (CL) 9.45 (11%) l.h(-1) .70 kg(-1) , and
      intercompartment clearances Q2 325 (21%) l.h(-1) .70 kg(-1) and Q3 136 (14%) l.h(
      1) .70 kg(-1) . EDDP formation clearance was 9.1 (11%) l.h(-1) .70 kg(-1) ,
      formation clearance of EMDP from EDDP 7.4 (63%) l.h(-1) .70 kg(-1) , elimination
      clearance of EDDP was 40.9 (26%) l.h(-1) .70 kg(-1) and the rate constant for
      intermediate compartments 2.17 (43%) h(-1) . CONCLUSIONS: Current pharmacokinetic
      parameter estimates in children and neonates are similar to those reported in
      adults. There was no clearance maturation with age. Neonatal enantiomer
      clearances were similar to those described in adults. A regimen of 0.2 mg.kg(-1)
      per 8 h in neonates achieves a target concentration of 0.06 mg.l(-1) within 36 h.
      Infusion, rather than intermittent dosing, should be considered if this target is
      to be achieved in older children after cardiac surgery.

PMID- 24666688
TI  - Normal values for heart rate variability parameters in children 6-8 years of age:
      the PANIC Study.
AB  - BACKGROUND: Measurement of heart rate variability (HRV) is a useful method for
      examining cardiac autonomic control. HRV has been measured in many studies among
      adults, but research on this topic among children is limited. We therefore
      defined reference values for a large number of HRV parameters among children.
      METHODS: The subjects were a population sample of 465 mainly prepubertal children
      6-8 years of age. Electrocardiogram (ECG) was recorded at rest, and 1- and 5-min
      ECG samples were selected for HRV analyses. HRV data were analysed in boys and
      girls separately to study possible gender differences in HRV parameters.
      Pearson's coefficients for correlation of age, maturity stage, height, weight and
      body mass index - standard deviation score (BMI-SDS) with HRV parameters were
      computed to study whether these factors confounded the definition of the
      reference values for HRV parameters. RESULTS: We found no statistically
      significant differences in HRV parameters between genders. Therefore, we defined
      the reference values for all HRV parameters as 5th, 25th, 50th, 75th and 95th
      percentiles from the ECG samples in all children, but not in boys and girls
      separately. Age, maturity stage, height, weight and BMI-SDS had weak, if any,
      associations with HRV parameters, suggesting that they did not confound the
      definition of the reference values. CONCLUSION: Same reference values for HRV
      parameters can be used in boys and girls. Although 5-min ECG recordings are
      preferable for measuring HRV, also 1-min recordings provide reliable data on most
      HRV parameters, especially those that mainly describe cardiac parasympathetic
      regulation.

PMID- 24666690
TI  - Energy intake, growth rate and body composition of young Labrador Retrievers and
      Miniature Schnauzers fed different dietary levels of vitamin A.
AB  - Research in rodents has shown that dietary vitamin A reduces body fat by
      enhancing fat mobilisation and energy utilisation; however, their effects in
      growing dogs remain unclear. In the present study, we evaluated the development
      of body weight and body composition and compared observed energy intake with
      predicted energy intake in forty-nine puppies from two breeds (twenty-four
      Labrador Retriever (LAB) and twenty-five Miniature Schnauzer (MS)). A total of
      four different diets with increasing vitamin A content between 5.24 and 104.80
      MUmol retinol (5000-100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable
      energy were fed from the age of 8 weeks up to 52 (MS) and 78 weeks (LAB). The
      daily energy intake was recorded throughout the experimental period. The body
      condition score was evaluated weekly using a seven-category system, and food
      allowances were adjusted to maintain optimal body condition. Body composition was
      assessed at the age of 26 and 52 weeks for both breeds and at the age of 78 weeks
      for the LAB breed only using dual-energy X-ray absorptiometry. The growth curves
      of the dogs followed a breed-specific pattern. However, data on energy intake
      showed considerable variability between the two breeds as well as when compared
      with predicted energy intake. In conclusion, the data show that energy intakes of
      puppies particularly during early growth are highly variable; however, the growth
      pattern and body composition of the LAB and MS breeds are not affected by the
      intake of vitamin A at levels up to 104.80 MUmol retinol (100 000 IU vitamin
      A)/4184 kJ (1000 kcal).

PMID- 24666691
TI  - In the parents' view: weight perception accuracy, disturbed eating patterns and
      mental health problems among young adolescents.
AB  - BACKGROUND: An accurate weight perception has been associated with motivation to
      change eating habits in the case of under- or overweight. However, recent studies
      have reported frequent misperceptions among parents and their offspring, both in
      the form of under- and overestimation of weight status. The aim of the present
      study was to investigate weight perception accuracy among parents of young
      adolescents in relation to reports on disturbed eating patterns and mental health
      problems. METHODS: Weight perception accuracy was assessed among parents of young
      adolescents (N = 5,781, aged 11 - 13 years) who participated in the ongoing
      Bergen Child Study (BCS). Parental weight perception was classified in
      overestimation, underestimation and accurate. Other measures included demographic
      variables, the parents' evaluations of disturbed eating patterns and mental
      health problems among their offspring as well as the adolescents' own weight
      perception accuracy. RESULTS: The parents accurately perceived more than 80% of
      normal weight adolescents, but nearly 60% of the underweight adolescents were
      overestimated, and a substantial proportion of overweight girls (34. 8%) and boys
      (12.8%) were underestimated. In general, parents who were aware of deviations
      from average weight in their child also reported higher levels of disturbed
      eating patterns, emotional problems, and behavioral problems. After controlling
      for demographic factors, the risk of parental over- and underestimation was
      significantly predicted by weight status, the adolescents' weight perception
      accuracy as well as disturbed eating patterns reported by the parents (p < .05).
      CONCLUSIONS: Adolescents with under- or overweight proved most likely to be
      misperceived by their parents in this study. The pattern of perceptually
      correcting deviations from normal weight was interpreted as a positivity bias
      among the parents. These results suggest that weight perception accuracy should
      be targeted in family-focused interventions in order to strengthen adequate
      weight control among young adolescents.

PMID- 24666689
TI  - Field evaluation of a new antibody-based diagnostic for Schistosoma haematobium
      and S. mansoni at the point-of-care in northeast Zimbabwe.
AB  - BACKGROUND: Rapid diagnostic tests (RDTs) for use at the point-of-care (POC) are
      likely to become increasingly useful as large-scale control programmes for
      schistosomiasis get underway. Given the low sensitivity of the reference standard
      egg count methods in detecting light infections, more sensitive tests will be
      required to monitor efforts aimed at eliminating schistosomiasis as advocated by
      the World Health Assembly Resolution 65.21 passed in 2012. METHODS: A recently
      developed RDT incorporating Schistosoma mansoni cercarial transformation fluid
      (SmCTF) for detection of anti-schistosome antibodies in human blood was here
      evaluated in children (mean age: 7.65 years; age range: 1-12 years) carrying
      light S. mansoni and S. haematobium infections in a schistosome-endemic area of
      Zimbabwe by comparison to standard parasitological techniques (i.e. the Kato-Katz
      faecal smear and urine filtration). Enzyme-linked immunosorbent assays (ELISAs)
      incorporating S. haematobium antigen preparations were also employed for
      additional comparison. RESULTS: The sensitivity of the SmCTF-RDT compared to
      standard parasitological methods was 100% while the specificity was 39.5%. It was
      found that the sera from RDT "false-positive" children showed significantly
      higher antibody titres in IgM-cercarial antigen preparation (CAP) and IgM-soluble
      egg antigen (SEA) ELISA assays than children identified by parasitology as "true
      negatives". CONCLUSIONS: Although further evaluations are necessary using more
      accurate reference standard tests, these results indicate that the RDT could be a
      useful tool for the rapid prevalence-mapping of both S. mansoni and S.
      haematobium in schistosome-endemic areas. It is affordable, user-friendly and
      allows for diagnosis of both schistosome species at the POC.

PMID- 24666692
TI  - Sulforhodamine 101 selectively labels human astrocytoma cells in an animal model
      of glioblastoma.
AB  - Sulforhodamine 101 (SR101) is a useful tool for immediate staining of astrocytes.
      We hypothesized that if the selectivity of SR101was maintained in astrocytoma
      cells, it could prove useful for glioma research. Cultured astrocytoma cells and
      acute slices from orthotopic human glioma (n=9) and lymphoma (n=6) xenografts
      were incubated with SR101 and imaged with confocal microscopy. A subset of slices
      (n=18) were counter-immunostained with glial fibrillary acidic protein and CD20
      for stereological assessment of SR101 co-localization. SR101 differentiated
      astrocytic tumor cells from lymphoma cells. In acute slices, SR101 labeled 86.50%
      (+/-1.86; p<0.0001) of astrocytoma cells and 2.19% (+/-0.47; p<0.0001) of
      lymphoma cells. SR101-labeled astrocytoma cells had a distinct morphology when
      compared with in vivo astrocytes. Immediate imaging of human astrocytoma cells in
      vitro and in ex vivo rodent xenograft tissue labeled with SR101 can identify
      astrocytic tumor cells and help visualize the tumor margin. These features are
      useful in studying astrocytoma in the laboratory and may have clinical
      applications.

PMID- 24666694
TI  - Widespread endotheliopathy in adults with cyanotic congenital heart disease.
AB  - INTRODUCTION: Cyanotic congenital heart disease is associated with functional
      limitation and vascular events. The nature and extent of endothelial dysfunction
      in cyanotic adults is poorly understood. We sought to characterise endothelial
      function in this setting. METHODS: A total of fourteen adults with cyanotic
      congenital heart disease (40+/-3 years) together with age- and sex-matched
      healthy controls underwent assessment of nitric oxide-dependent vascular
      responses, including flow-mediated dilatation of the brachial artery and dynamic
      vessel analysis of the retina in response to flickering light. Plasma levels of
      the endothelium-derived vasoconstrictor endothelin-1 and the nitric oxide
      antagonist, asymmetric dimethylarginine, were measured. Circulating endothelial
      progenitor cells were assessed by flow cytometry. RESULTS: Flow-mediated
      dilatation was significantly lower in cyanosed adults than controls (4.0+/-0.8
      versus 7.2+/-1.0%, p=0.019, n=11 per group). Retinal arterial and venous dilatory
      responses were also impaired (2.9+/-0.8 versus 5.0+/-0.6%, p=0.05 and 3.4+/-0.3
      versus 5.2+/-0.7%, p=0.04, n=13). Serum levels of endothelin-1 and asymmetric
      dimethylarginine were higher in cyanosed adults (3.0+/-0.6 versus 1.1+/-0.1
      pg/ml, p=0.004 and 0.68+/-0.05 versus 0.52+/-0.02 MUmol/L, p=0.03, n=11).
      Endothelial progenitor cells (CD34+CD45dimCD133+KDR+) were reduced in those with
      chronic cyanosis (17+/-4 versus 40+/-6 per million white blood cells, p=0.005,
      n=11). CONCLUSIONS: Endothelial function is impaired in the systemic arteries and
      retinal vessels in adults with cyanotic congenital heart disease, suggesting a
      widespread endotheliopathy. Diminished numbers of endothelial progenitor cells
      might potentially contribute to these observations.

PMID- 24666693
TI  - Structures of the Leishmania infantum polymerase beta.
AB  - Protozoans of the genus Leishmania, the pathogenic agent causing leishmaniasis,
      encode the family X DNA polymerase Li Pol beta. Here, we report the first crystal
      structures of Li Pol beta. Our pre- and post-catalytic structures show that the
      polymerase adopts the common family X DNA polymerase fold. However, in contrast
      to other family X DNA polymerases, the dNTP-induced conformational changes in Li
      Pol beta are much more subtle. Moreover, pre- and post-catalytic structures
      reveal that Li Pol beta interacts with the template strand through a
      nonconserved, variable region known as loop3. Li Pol beta Deltaloop3 mutants
      display a higher catalytic rate, catalytic efficiency and overall error rates
      with respect to WT Li Pol beta. These results further demonstrate the subtle
      structural variability that exists within this family of enzymes and provides
      insight into how this variability underlies the substantial functional
      differences among their members.

PMID- 24666696
TI  - Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with
      refractory chronic cough: a double-blind randomized controlled trial.
AB  - BACKGROUND: Inhalation of capsaicin, the extract of hot chili peppers, induces
      coughing in both animals and human subjects through activation of transient
      receptor potential vanilloid 1 (TRPV1) on airway sensory nerves. Therefore the
      TRPV1 receptor is an attractive target for the development of antitussive agents.
      OBJECTIVE: We sought to assess the antitussive effect of TRPV1 antagonism in
      patients with refractory chronic cough. METHODS: Twenty-one subjects with
      refractory chronic cough (>8 weeks) attending a specialist clinic were recruited
      to a randomized, double-blind, placebo-controlled crossover trial assessing a
      TRPV1 antagonist (SB-705498). Cough reflex sensitivity to capsaicin
      (concentration of capsaicin inducing at least 5 coughs) and 24-hour cough
      frequency were coprimary end points assessed after a single dose of SB-705498
      (600 mg) and matched placebo. Cough severity and urge to cough were reported on
      visual analog scales, and cough-specific quality of life data were also
      collected. RESULTS: Treatment with SB-705498 produced a significant improvement
      in cough reflex sensitivity to capsaicin at 2 hours and a borderline significant
      improvement at 24 hours compared with placebo (adjusted mean difference of +1.3
      doubling doses at 2 hours [95% CI, +0.3 to +2.2; P = .0049] and +0.7 doubling
      doses at 24 hours [95% CI, +0.0 to +1.5; P = .0259]). However, 24-hour objective
      cough frequency was not improved compared with placebo. Patient-reported cough
      severity, urge to cough, and cough-specific quality of life similarly suggested
      no effect of SB-705498. CONCLUSION: This study raises important questions about
      both the role of TRVP1-mediated mechanisms in patients with refractory chronic
      cough and also the predictive value of capsaicin challenge testing in the
      assessment of novel antitussive agents.

PMID- 24666697
TI  - Ruptured urinary bladder attributable to urethral compression by a haematoma
      after vertebral fracture in a bull.
AB  - BACKGROUND: In male cattle, rupture of the urinary bladder is usually associated
      with urethral obstruction by uroliths. Less common causes include urethral
      compression or stricture. This case report describes the findings in a young
      Limousion breeding bull with rupture of the urinary bladder because of urethral
      compression by a haematoma after coccygeal fracture. CASE PRESENTATION: The bull
      had been introduced into a 40-head Red-Holstein herd one week before being
      injured. One week after introduction to the herd, the bull had an acute onset of
      anorexia and he was referred to the clinic. There was marked abdominal
      distension, reduced skin turgor and enophthalmus. The serum concentration of urea
      and creatinine was increased. Ultrasonographic examination revealed severe
      ascites and abdominocentesis yielded clear yellow fluid with high urea and
      creatinine concentrations, which supported a diagnosis of uroperitoneum. The bull
      was euthanatized because of a poor prognosis. Postmortem examination revealed a
      comminuted fracture of the first two coccygeal vertebrae associated with a
      massive haematoma that obstructed entire pelvic cavity. The haematoma compressed
      the urethra thereby preventing outflow of urine, which resulted in a 5-cm tear
      ventrally at the neck of the bladder. It was assumed that the newly-introduced
      bull had sustained the vertebral fractures when he was mounted by a cow.
      CONCLUSIONS: The present case study serves to expand the differential diagnosis
      of urinary bladder rupture. Therefore, in addition to obstructive urolithiasis,
      compression and stricture of the urethra might be considered in male cattle with
      uroperitoneum.

PMID- 24666698
TI  - Postoperative pain in complex ophthalmic surgical procedures: comparing practice
      with guidelines.
AB  - OBJECTIVE: To analyze the management of postoperative pain after complex
      ophthalmic surgery and to compare it to the guidelines. DESIGN: A retrospective
      study. SETTING: University Hospital Split, Croatia. SUBJECTS: Patients (N = 447)
      who underwent complex ophthalmic surgical procedures from 2008 to 2012. METHODS:
      The following data were extracted from patient medical records: age, gender, type
      and dosage of premedication, preoperative patient's physical status, type of
      procedure, duration of procedure-surgical and anesthesia time, type and dosage of
      anesthesia, the type and dosage of postoperative analgesia for each postoperative
      day. RESULTS: None of the patients had information about pain intensity in their
      records. There were 90% patients who did not receive any medication the night
      before surgery, 54% did not receive any premedication immediately before surgery,
      19% did not receive any pain medication after the surgery in the operating room
      and 46% of patients did not receive any analgesics after being released to the
      ophthalmology department. Among those who received analgesia after surgery, 98%
      received only one dose of an analgesic, and 93% of patients received analgesia
      only on the day of the surgery. Furthermore, patients were returned to the
      department immediately after surgery, without intensive monitoring. During the
      analyzed five years there were no educational session organized by
      anesthesiologist to the ophthalmic surgeons. CONCLUSIONS: Postoperative pain
      management and perioperative care of patients undergoing major ophthalmic surgery
      indicates lack of attention towards pain intensity and postoperative analgesia.
      Appropriate interventions should be employed to improve postoperative pain
      management, to facilitate patient recovery.

PMID- 24666695
TI  - Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in
      the absence of allergic inflammation.
AB  - BACKGROUND: Although eosinophilic inflammation typifies allergic asthma, it is
      not a prerequisite for airway hyperresponsiveness (AHR), suggesting that
      underlying abnormalities in structural cells, such as airway smooth muscle (ASM),
      contribute to the asthmatic diathesis. Dysregulation of procontractile G protein
      coupled receptor (GPCR) signaling in ASM could mediate enhanced contractility.
      OBJECTIVE: We explored the role of a regulator of procontractile GPCR signaling,
      regulator of G protein signaling 5 (RGS5), in unprovoked and allergen-induced
      AHR. METHODS: We evaluated GPCR-evoked Ca(2+) signaling, precision-cut lung slice
      (PCLS) contraction, and lung inflammation in naive and Aspergillus fumigatus
      challenged wild-type and Rgs5(-/-) mice. We analyzed lung resistance and dynamic
      compliance in live anesthetized mice using invasive plethysmography. RESULTS:
      Loss of RGS5 promoted constitutive AHR because of enhanced GPCR-induced Ca(2+)
      mobilization in ASM. PCLSs from naive Rgs5(-/-) mice contracted maximally at
      baseline independently of allergen challenge. RGS5 deficiency had little effect
      on the parameters of allergic inflammation, including cell counts in
      bronchoalveolar lavage fluid, mucin production, ASM mass, and subepithelial
      collagen deposition. Unexpectedly, induced IL-13 and IL-33 levels were much lower
      in challenged lungs from Rgs5(-/-) mice relative to those seen in wild-type mice.
      CONCLUSION: Loss of RGS5 confers spontaneous AHR in mice in the absence of
      allergic inflammation. Because it is selectively expressed in ASM within the lung
      and does not promote inflammation, RGS5 might be a therapeutic target for asthma.

PMID- 24666699
TI  - Changes in the activity and expression of protein phosphatase-1 accompany the
      differential regulation of NHE3 before and after the onset of hypertension in
      spontaneously hypertensive rats.
AB  - AIM: The Na(+) /H(+) exchanger NHE3 activity decreases in the proximal tubule of
      spontaneously hypertensive rats (SHRs) as blood pressure increases, and this
      reduction is correlated with higher NHE3 phosphorylation levels at the PKA
      consensus site serine 552. This study tested the hypothesis that this lowered
      NHE3 activity is associated with an increase in PKA activity and expression,
      and/or a decrease in protein phosphatase-1 (PP1) activity and expression.
      METHODS: Proximal tubule NHE3 activity was measured as the rate of bicarbonate
      reabsorption by stationary microperfusion. NHE3 phosphorylation and protein
      expression were determined by immunoblotting. PKA and PP1 activities were
      determined using specific substrates under optimal enzymatic conditions. RESULTS:
      The PKA activator, 6-MB-cAMP, increased the phosphorylation levels of NHE3 at
      serine 552 in the renal cortex; this increase happens to a much greater extent in
      young pre-hypertensive SHRs (Y-SHRs) compared to adult SHRs with established
      hypertension (A-SHRs). Likewise, the inhibitory effect of 6-MB-cAMP on NHE3
      transport activity was much more pronounced in the proximal tubules of Y-SHRs
      than in those of A-SHRs. Renal cortical activity of PKA was not significantly
      different between Y-SHRs and A-SHRs. On the other hand, Y-SHRs exhibited higher
      protein phosphatase 1 (PP1) activity, and their expression of the PP1 catalytic
      subunit PP1alpha in the renal cortex was also higher than in A-SHRs. CONCLUSION:
      Collectively, these results support the idea that the lower NHE3 transport
      activity and higher phosphorylation occurring after the development of
      hypertension in SHRs are due, at least in part, to reduced PP1-mediated
      dephosphorylation of NHE3 at serine 552.

PMID- 24666700
TI  - MALDI-TOF MS identification of anaerobic bacteria: assessment of pre-analytical
      variables and specimen preparation techniques.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) has emerged as a tool for identifying clinically relevant
      anaerobes. We evaluated the analytical performance characteristics of the Bruker
      Microflex with Biotyper 3.0 software system for identification of anaerobes and
      examined the impact of direct formic acid (FA) treatment and other pre-analytical
      factors on MALDI-TOF MS performance. A collection of 101 anaerobic bacteria were
      evaluated, including Clostridium spp., Propionibacterium spp., Fusobacterium
      spp., Bacteroides spp., and other anaerobic bacterial of clinical relevance. The
      results of our study indicate that an on-target extraction with 100% FA improves
      the rate of accurate identification without introducing misidentification
      (P<0.05). In addition, we modify the reporting cutoffs for the Biotyper "score"
      yielding acceptable identification. We found that a score of >=1.700 can maximize
      the rate of identification. Of interest, MALDI-TOF MS can correctly identify
      anaerobes grown in suboptimal conditions, such as on selective culture media and
      following oxygen exposure. In conclusion, we report on a number of simple and
      cost-effective pre- and post-analytical modifications could enhance MALDI-TOF MS
      identification for anaerobic bacteria. 

PMID- 24666701
TI  - Comparison of VITEK2, MALDI-TOF MS, and 16S rDNA sequencing for identification of
      Myroides odoratus and Myroides odoratimimus.
AB  - The genus Myroides comprises the 2 medically relevant species Myroides odoratus
      and Myroides odoratimimus that are rare opportunistic pathogens and cause
      infections in immunocompromised patients. A fast identification of Myroides is of
      importance because these bacterial strains show multiple resistance against
      antibiotics and therefore limit treatment options. They are associated, for
      instance, with urinary tract infections, sepsis, meningitis, pneumonia, and
      infectious cellulitis. Since more and more Myroides spp. are being described,
      additional potentially pathogenic bacteria may be identified in the future
      demanding the need for fast and reliable identification methods at species level.
      However, to date, only molecular approaches meet these demands. In this study,
      we, therefore, attempt to define an appropriate method other than DNA
      fingerprinting that will permit a comparable efficacy and, possibly, a more
      economical strain identification. For this purpose, we compared 2 widely used
      automated diagnostic systems (VITEK 2 [bioMerieux, Nurtingen, Germany] and Matrix
      Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF
      MS) [Bruker Daltonics, Bremen, Germany]) and correlated the results to 16S rDNA
      sequencing data. In total, we analyzed 22 strains collected in the course of
      routine diagnostics. In this study, we demonstrate that VITEK 2 reliably
      identifies the genus Myroides but cannot differentiate between M. odoratimimus
      and M. odoratus. In contrast to this, both MALDI-TOF MS and 16S rDNA sequencing
      efficiently distinguish between the 2 species. 

PMID- 24666702
TI  - FilmArray(r) respiratory panel performance in respiratory samples from neonatal
      care units.
AB  - FilmArray Respiratory Panel (RP) (Idaho Technology, Inc., Salt Lake City, UT,
      USA) performance was retrospectively evaluated in respiratory samples collected
      from neonates in 2 reference neonatology units. Using the FilmArray RP assay,
      121/152 (79.6%) samples were positive for at least 1 respiratory virus, while
      31/152 (20.4%) were negative. FilmArray RP results were concordant in 68/72
      (94.4%) respiratory samples tested with laboratory-developed real-time PCR
      assays, while in 4/72 (5.6%) samples, the FilmArray RP assay detected an
      additional virus (2 human rhinovirus/enterovirus and 2 bocavirus). In addition,
      FilmArray RP results for 70 of 80 (87.5%) respiratory samples tested were
      concordant with the Seegene Seeplex RV15(r) detection assay (Seegene, Inc.,
      Seoul, South Korea), while 10/80 (12.5%) were discordant. The advantages of the
      FilmArray RP are the rapid detection of respiratory viruses (1 hour), the wide
      number of pathogens detectable in a single assay, and the reduced hands-on time. 

PMID- 24666703
TI  - A rapid ELISA for the diagnosis of MB leprosy based on complementary detection of
      antibodies against a novel protein-glycolipid conjugate.
AB  - Despite the widespread use of multidrug therapy for treatment, delays in clinical
      recognition and under-reporting of leprosy indicate that Mycobacterium leprae
      transmission is continuing. Thus, leprosy is likely to persist as a significant
      burden on health systems in many regions. In this study, we combined 2 previously
      characterized leprosy antigens, leprosy IDRI diagnostic-1 (LID-1) and ND-O, into
      the single fusion complex (ND-O-LID) and determined the serum antibody responses
      of leprosy patients from Colombia and the Philippines. Following confirmation
      that antibodies recognized each component within the conjugate, we assessed the
      performance of a rapid enzyme-linked immunosorbent assay (ELISA) system (Leprosy
      Detect(TM) fast ELISA; InBios International, Inc., Seattle, WA, USA) based on ND
      O-LID capable of generating results within 1.5hours of sample addition. We found
      ELISA results correlated with the bacteriological index and Ridley-Jopling
      categorization, with lepromatous leprosy patients having the highest responses,
      while those of borderline tuberculoid patients were lower. Multibacillary (MB)
      leprosy patients were distinguished with a high degree of sensitivity (95.7%) and
      specificity (93.2%), suggesting that this ELISA could potentially replace
      invasive and insensitive skin slit smear procedures that require expert
      microscopic examinations. Due to the speed and robustness of this assay, we
      believe this is an excellent tool for detecting MB leprosy patients in a simple
      and highly-quantitative manner. 

PMID- 24666704
TI  - Candidemia surveillance in Iowa: emergence of echinocandin resistance.
AB  - We performed prospective surveillance for candidemia at 14 Iowa hospitals in 2011
      2012. A total of 163 episodes were analyzed. Candida albicans (n = 69 [42%]) and
      Candida glabrata (n = 58 [36%]) were the most common species. Antifungal
      resistance was uncommon; 9% of C. glabrata were fluconazole resistant, and 5% (3
      isolates) were intermediate or resistant to 1 or more of the echinocandins.
      Molecular analyses of the fks1 and fks2 hotspots of the C. glabrata revealed no
      mutations except in 2 of these 3 isolates (L628R and S629P in fks1). Compared
      with previous surveillance performed in 1998-2001, there was a decrease in
      proportion of candidemia due to C. albicans (58 to 42%) and an increased
      proportion due to C. glabrata (20 to 36%). Further emergence of echinocandin
      resistance among the increasingly common species C. glabrata would complicate the
      management of this life-threatening infection. 

PMID- 24666705
TI  - Association between viral load of varicella zoster virus in cerebrospinal fluid
      and the clinical course of central nervous system infection.
AB  - Varicella zoster virus (VZV) like other alphaherpes viruses stays latent after
      its primary infection. During its reactivation, it can infect the central nervous
      system (CNS) causing a variety of clinical presentations. Using polymerase chain
      reaction (PCR) for detection of VZV DNA in cerebrospinal fluid (CSF), it is now
      recognized in some series as the most common causative agent of viral CNS
      infection. We aimed to investigate in our study the correlation between VZV viral
      load in the CSF and the clinical course of its infection, using quantitative real
      time PCR. For this purpose, we examined 56 specimens of consecutive patients with
      positive CSF for VZV DNA in a qualitative test, with a clinical picture of
      meningitis or encephalitis collected over 10years in Rambam medical center. We
      found a significant correlation between VZV viral load and the severity and
      duration of neurological disease. We believe that using quantitative measurement
      of VZV DNA in the CSF, could serve as a prognostic marker which would influence
      treatment decisions. 

PMID- 24666706
TI  - Association of clinical and demographic factors in invasive candidiasis caused by
      fluconazole-resistant Candida species: a study in 15 hospitals, Medellin,
      Colombia 2010-2011.
AB  - Candida is the most important agent of fungal infections. Several risk factors
      have been described associated with invasive infection by fluconazole-resistant
      Candida spp. A prospective cross-sectional study with case-control analysis was
      conducted. Case group patients with fluconazole-resistant Candida isolate were
      included; control group were patients with fluconazole-susceptible Candida spp. A
      multivariate logistic regression model was performed. Three hundred isolates of
      Candida spp. were analyzed. Most frequent species were Candida albicans/Candida
      dubliniensis (48.3%) and Candida tropicalis (22.3%). Posaconazole susceptibility
      was 93.7%; voriconazole, 84%; and fluconazole, 78.7%. Susceptibility to
      anidulafungin and caspofungin was 92.7% and 92.3%, respectively. Neutropenia
      (adjusted odds ratio [aOR] 6.5, 95% confidence interval [CI] 1.0-43.1),
      antifungal exposure (aOR 5.1, 95% CI 2.3-11.2), and antituberculosis therapy (aOR
      7.7, 95% CI 1.4-43.2) were associated to fluconazole resistance. Susceptibility
      results are useful to guide the selection of empiric antifungal treatment and the
      design of local therapeutic guidelines. Previous antifungal exposure suggests
      possible resistance to fluconazole, pointing towards the selection of a different
      class of antifungal agents. 

PMID- 24666707
TI  - Detection of high-risk human papillomavirus type 16 and 18 using isothermal
      helicase-dependent amplification.
AB  - Persistent infection with human papillomavirus (HPV) induces cervical cancer.
      Here, we describe a sensitive, specific, and rapid assay for high-risk HPV16 and
      18 detection by isothermal helicase-dependent amplification. This method can be
      used as cost-effective diagnostic method for low-income countries, where highest
      incidences worldwide of cervical cancer are registered. 

PMID- 24666708
TI  - Differences in the age-drug use curve among students and non-students in the UK.
AB  - INTRODUCTION AND AIMS: The aim of this study is to assess whether the delayed
      peak in the age-drug use prevalence curve among college students compared with
      non-college students observed in studies in the USA would be replicated in the
      UK. DESIGN AND METHODS: The analysis was based on data collected as part of the
      Crime Survey for England and Wales 2010-2011, a national general household survey
      of young people and adults. A random sample of approximately 26 000 respondents
      was asked questions covering use of 19 drugs. RESULTS: The study provides
      evidence of a delayed age-drug use peak among students compared with non-students
      of similar age. During the period of age 20-22, drug use prevalence among
      students was similar to, or higher than, that of non-students. The relationship
      of student status and elevated drug use only occurred during the narrow age range
      associated with emerging adulthood (ages 20-22). University attendance before or
      after this period was not associated with higher prevalence rates among students
      compared with non-students. DISCUSSION AND CONCLUSION: Explanations of the age
      drug use peak among students would need to take into account that university
      attendance alone might not result in higher drug use prevalence rates. This would
      mean that explanations that focus on the interaction between university life and
      emerging adulthood might provide the most promising lines of enquiry.

PMID- 24666709
TI  - Maternal high-fat diet consumption modulates hepatic lipid metabolism and
      microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring.
AB  - Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is
      closely related to hepatic lipid accumulation, insulin resistance and increased
      serum cytokine levels in offspring and into their adulthood. MicroRNA (miRNA)
      have been implicated in cholesterol biosynthesis and fatty acid metabolism. We
      evaluated the modulation of hepatic fatty acid synthesis (de novo), beta
      oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in
      recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard
      chow (SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice
      weighed more, had a larger adipose tissue mass and were more intolerant to
      glucose and insulin (P< 0.05). HFD-O mice also presented more levels of serum
      cholesterol, TAG, NEFA and hepatic IkappaB kinase and c-Jun N-terminal kinase
      phosphorylation compared with SC-O mice (P< 0.05). Protein levels of fatty acid
      synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase
      were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and
      protein were more abundant in HFD-O mice than in SC-O mice (P< 0.05).
      Interestingly, mRNA expression levels of the beta-oxidation-related genes ACADVL
      and CPT1 were decreased in HFD-O mice (P< 0.05). Furthermore, the expression of
      miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with
      that in SC-O mice (P< 0.05). Changes in hepatic lipid metabolism were accompanied
      by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P< 0.05).
      Taken together, the present results strongly suggest that maternal consumption of
      a HFD affects the early lipid metabolism of offspring by modulating the
      expression of hepatic beta-oxidation-related genes and miRNA that can contribute
      to metabolic disturbances in adult life.

PMID- 24666710
TI  - Peroxidase gene discovery from the horseradish transcriptome.
AB  - BACKGROUND: Horseradish peroxidases (HRPs) from Armoracia rusticana have long
      been utilized as reporters in various diagnostic assays and histochemical
      stainings. Regardless of their increasing importance in the field of life
      sciences and suggested uses in medical applications, chemical synthesis and other
      industrial applications, the HRP isoenzymes, their substrate specificities and
      enzymatic properties are poorly characterized. Due to lacking sequence
      information of natural isoenzymes and the low levels of HRP expression in
      heterologous hosts, commercially available HRP is still extracted as a mixture of
      isoenzymes from the roots of A. rusticana. RESULTS: In this study, a normalized,
      size-selected A. rusticana transcriptome library was sequenced using 454 Titanium
      technology. The resulting reads were assembled into 14871 isotigs with an average
      length of 1133 bp. Sequence databases, ORF finding and ORF characterization were
      utilized to identify peroxidase genes from the 14871 isotigs generated by de novo
      assembly. The sequences were manually reviewed and verified with Sanger
      sequencing of PCR amplified genomic fragments, resulting in the discovery of 28
      secretory peroxidases, 23 of them previously unknown. A total of 22 isoenzymes
      including allelic variants were successfully expressed in Pichia pastoris and
      showed peroxidase activity with at least one of the substrates tested, thus
      enabling their development into commercial pure isoenzymes. CONCLUSIONS: This
      study demonstrates that transcriptome sequencing combined with sequence motif
      search is a powerful concept for the discovery and quick supply of new enzymes
      and isoenzymes from any plant or other eukaryotic organisms. Identification and
      manual verification of the sequences of 28 HRP isoenzymes do not only contribute
      a set of peroxidases for industrial, biological and biomedical applications, but
      also provide valuable information on the reliability of the approach in
      identifying and characterizing a large group of isoenzymes.

PMID- 24666711
TI  - The fabella syndrome - a rare cause of posterolateral knee pain: a review of the
      literature and two case reports.
AB  - BACKGROUND: The purpose of this article was to evaluate the risks and benefits of
      non-operative treatment versus surgical excision of a fabella causing
      posterolateral knee pain. We performed a systematic review of literature and also
      present two case reports.Twelve publications were found in a PubMed literature
      review searching the word "fabella syndrome". Non-operative treatment and
      surgical excision of the fabella has been described. CASE PRESENTATION: Two
      patients presented to our outpatient clinic with persisting posterolateral knee
      pain. In both cases the presence of a fabella was identified, located in close
      proximity to the posterolateral femoral condyle. All other common causes of intra
      and extra articular pathologies possibly causing the posterolateral knee pain
      were excluded.Following failure to respond to physiotherapy both patients
      underwent arthroscopy which excluded other possible causes for posterolateral
      knee pain. The decision was made to undertake surgical excision of the fabella in
      both cases without complication.Both patients were examined 6 month and one year
      after surgery with the Tegner activity score, the Visual Analogue Scale (VAS),
      and International Knee Documentation Committee Score (IKDC). CONCLUSION:
      Consistent posterolateral pain during exercise might indicate the presence of a
      fabella syndrome. Resecting the fabella can be indicated and is a minor surgical
      procedure with minimal risk. Despite good results in the literature
      posterolateral knee pain can persist and prevent return to a high level of
      sports. LEVEL OF EVIDENCE: IV, case reports and analysis of literature.

PMID- 24666712
TI  - Viral coinfection in childhood respiratory tract infections.
AB  - INTRODUCTION: The introduction of molecular techniques has enabled better
      understanding of the etiology of respiratory tract infections in children. The
      objective of the study was to analyze viral coinfection and its relationship to
      clinical severity. METHODS: Hospitalized pediatric patients with a clinical
      diagnosis of respiratory infection were studied during the period between 2009
      2010. Clinical and epidemiological data, duration of hospitalization, need for
      oxygen therapy, bacterial coinfection and need for mechanical ventilation were
      collected. Etiology was studied by multiplex PCR and low-density microarrays for
      19 viruses. RESULTS: A total of 385 patients were positive, 44.94% under 12
      months. The most frequently detected viruses were RSV-B: 139, rhinovirus: 114,
      RSV-A: 111, influenza A H1N1-2009: 93 and bocavirus: 77. Coinfection was detected
      in 61.81%, 36.36% with 2 viruses, 16.10% and 9.35% with 3 to 4 or more.
      Coinfection was higher in 2009 with 69.79 vs. 53.88% in 2010. Rhinovirus/RSV-B on
      10 times and RSV-A/RSV-B on 5 times were the most detected coinfections.
      Hospitalization decreased with greater number of viruses (P<0,001). Oxygen
      therapy was required by 26.75% (one virus was detected in 55.34% of cases). A
      larger number of viruses resulted in less need for oxygen (P<0,001). Ten cases
      required mechanical ventilation, 4 patients with bacterial coinfection and 5 with
      viral coinfection (P=0,69). CONCLUSIONS: An inverse relationship was found
      between the number of viruses detected in nasopharyngeal aspirate, the need for
      oxygen therapy and hospitalization days. More epidemiological studies and
      improved quantitative detection techniques are needed to define the role of viral
      coinfections in respiratory disease and its correlation with the clinical
      severity.

PMID- 24666713
TI  - The role of temperament and character in the outcome of depressive mood in eating
      disorders.
AB  - OBJECTIVES: The aims were to see which temperament and character dimensions were
      associated with depression, mainly with its outcome at two-year follow up in
      eating disorders (EDs). METHODS: Participants (N=151) were 44 Anorexia nervosa
      (AN), 55 Bulimia nervosa (BN) and 52 Eating disorders not otherwise specified
      (EDNOS) patients. The Beck Depression Inventory (BDI), State and Trait Anxiety
      Inventory (STAI), Rosenberg Self Esteem Questionnaire (RSE), Eating Disorder
      Inventory (EDI-2) and Temperament and Character Inventory (TCI) were
      administered. RESULTS: Depression at the beginning (t0) was severe in 22% of the
      cases. Harm Avoidance and Novelty Seeking had an effect on depressed mood at t0,
      mediated by Ineffectiveness. Responsibility (SD1) was associated with scores on
      the BDI at two-year follow up (beta=-0.37, 95% CI -2.6, -0.6, p<0.01).
      CONCLUSION: The evaluation of personality dimension in EDs has therapeutic and
      prognostic implications: To enhance self-efficacy and self-directness is crucial
      for good clinical outcome.

PMID- 24666714
TI  - Controlled shifting of attention in schizophrenia and bipolar disorder through a
      dichotic listening paradigm.
AB  - The dichotic listening (DL) task was developed originally to examine bottom-up or
      "automatic" information processing. More recently, however, it has been used as a
      tool in the study of top-down or "controlled" information processing. This has
      been done by including forced-choice conditions, wherein the examinee is required
      to focus attention on one or the other ear. It has been widely utilized with
      patients with schizophrenia, who exhibit rather severe deficits in managing their
      attention, but not with other patient groups, such as patients with bipolar
      disorder. In the present study, we examined potential performance similarities in
      the DL listening task. In total, the sample consisted of 38 patients with
      schizophrenia, 20 patients with psychotic bipolar disorder and 35 healthy
      individuals, who performed a DL task with verbal stimuli once at the beginning of
      their hospitalization and again on the last day before discharge. Our findings
      indicated that both patient groups showed similarly diminished performance when
      compared to healthy participants at both times of administration. Symptom
      improvement between the two evaluations did not significantly influence
      performance in the DL task. In conclusion, impaired automated and controlled
      information processing appears to be a common deficit in both schizophrenia and
      bipolar disorder. 

PMID- 24666715
TI  - The tridimensional personality of male heroin users treated with methadone in
      Taiwan.
AB  - It was our assumption that male heroin users have the personality traits of high
      impulsivity and low social interaction. Compliance regarding methadone
      maintenance therapy (MMT) is hypothesized to be related to personality features.
      We recruited 43 patients that had been receiving MMT and 43 healthy volunteers.
      All participants completed a Tridimensional Personality Questionnaire (TPQ).
      Information related to the Opiate Treatment Index (OTI) was gathered from the
      heroin group. The personality dimensions in the heroin user group and the control
      group were compared. We further investigated the association between TPQ and OTI.
      The heroin group presented with lower reward dependence than the control group.
      Regarding sub-dimensions, heroin users showed higher impulsivity and
      fatigability, and lower exploratory excitability and social dependence. The
      explosive (borderline) pattern was more common among the heroin users. The odds
      ratio of explosive pattern developing to heroin dependence was 4.19. Q scores of
      heroin use and the maximal methadone dose were associated with persistence. 

PMID- 24666716
TI  - Lifetime experiences of hypomanic symptoms are associated with delayed and
      irregular sleep-wake cycle and seasonality in non-clinical adult samples.
AB  - OBJECTIVES: Disturbances of the sleep-wake cycle and seasonality have been
      reported in patients with bipolar disorder (BD). Considering that BD seems to be
      a spectrum condition in terms of clinical and biological characteristics,
      circadian and seasonal rhythm related to BD could be detected in non-clinical
      individuals with subthreshold bipolarity. The aim of this study was to screen
      past hypomanic symptoms in non-clinical samples and investigate their association
      with deviated sleep-wake cycle and seasonality. METHODS: Lifetime history of
      hypomanic symptoms was assessed with the Hypomania Checklist-32 (HCL-32).
      Circadian preference, variability of sleep-wake time and seasonal changes in mood
      and behavior were evaluated on a lifetime-basis in non-clinical adult samples
      (n=313), using the Composite Scale of Morningness (CSM), the Sleep Timing
      Questionnaire (STQ), and the Seasonal Pattern Assessment Questionnaire (SPAQ).
      RESULTS: Two subdomains of hypomanic symptoms were identified through factor
      analysis of HCL-32, i.e., "active/elated" factor and "irritable/risk-taking"
      factor. The HCL-32 total score (p<0.001) and the "active/elated" factor score
      (p=0.028) were weakly correlated only with seasonality, whereas the
      "irritable/risk-taking" factor score was associated not only with seasonality
      (p<0.001), but also with evening preference (p<0.001) and irregularity of sleep
      wake times (p=0.001~0.011). CONCLUSION: Circadian and seasonal characteristics
      related to BD are also associated with a past history of hypomanic symptoms in
      non-clinical samples, especially "irritable/risk-taking" symptoms, suggesting the
      existence of subclinical presentation of BD and their biological traits.

PMID- 24666717
TI  - Validation of the University of Sao Paulo's Sensory Phenomena Scale -- English
      version.
AB  - INTRODUCTION: Sensory phenomena (SP) are disturbing sensations, feelings or
      urges. Although such feelings are often found in obsessive-compulsive disorder
      (OCD) and Tourette's Syndrome (TS) patients, sensory phenomena are usually not
      addressed in assessment measures. The University of Sao Paulo's Sensory Phenomena
      Scale (USP-SPS) was designed to measure sensory phenomena among all ages of
      patients with OCD and TS, and it was validated in Portuguese. OBJECTIVES: The aim
      of this study is to validate the English version of the USP-SPS and to examine
      its psychometric properties. MATERIAL AND METHODS: Sixty subjects, between the
      ages of 7 and 60 years, completed the USP-SPS, Y-BOCS or CY-BOCS and YGTSS. An
      expert clinician also performed a Clinical Inquiry about SP. Inter-rater
      reliability, sensitivity, specificity, convergent and divergent validity were
      evaluated. RESULTS: The USP-SPS symptom checklist showed good sensitivity in all
      ages, however its severity scale did not show good validity results for the
      pediatric population.

PMID- 24666718
TI  - Validity and applicability of a video-based animated tool to assess mobility in
      elderly Latin American populations.
AB  - AIM: To assess the reliability and the validity of Portuguese- and Spanish
      translated versions of the video-based short-form Mobility Assessment Tool in
      assessing self-reported mobility, and to provide evidence for the applicability
      of these videos in elderly Latin American populations as a complement to physical
      performance measures. METHODS: The sample consisted of 300 elderly participants
      (150 from Brazil, 150 from Colombia) recruited at neighborhood social centers.
      Mobility was assessed with the Mobility Assessment Tool, and compared with the
      Short Physical Performance Battery score and self-reported functional
      limitations. Reliability was calculated using intraclass correlation
      coefficients. Multiple linear regression analyses were used to assess
      associations among mobility assessment tools and health, and sociodemographic
      variables. RESULTS: A significant gradient of increasing Mobility Assessment Tool
      score with better physical function was observed for both self-reported and
      objective measures, and in each city. Associations between self-reported mobility
      and health were strong, and significant. Mobility Assessment Tool scores were
      lower in women at both sites. Intraclass correlation coefficients of the Mobility
      Assessment Tool were 0.94 (95% confidence interval 0.90-0.97) in Brazil and 0.81
      (95% confidence interval 0.66-0.91) in Colombia. Mobility Assessment Tool scores
      were lower in Manizales than in Natal after adjustment by Short Physical
      Performance Battery, self-rated health and sex. CONCLUSIONS: These results
      provide evidence for high reliability and good validity of the Mobility
      Assessment Tool in its Spanish and Portuguese versions used in Latin American
      populations. In addition, the Mobility Assessment Tool can detect mobility
      differences related to environmental features that cannot be captured by
      objective performance measures.

PMID- 24666719
TI  - PET quantification with a histogram derived total activity metric: superior
      quantitative consistency compared to total lesion glycolysis with absolute or
      relative SUV thresholds in phantoms and lung cancer patients.
AB  - INTRODUCTION: The increasing use of molecular imaging probes as biomarkers in
      oncology emphasizes the need for robust and stable methods for quantifying tracer
      uptake in PET imaging. The primary motivation for this research was to find an
      accurate method to quantify the total tumor uptake. Therefore we developed a
      histogram-based method to calculate the background subtracted lesion (BSL)
      activity and validated BSL by comparing the quantitative consistency with the
      total lesion glycolysis (TLG) in phantom and patient studies. METHODS: A thorax
      phantom and a PET-ACR quality assurance phantom were scanned with increasing FDG
      concentrations. Volumes of interest (VOIs) were placed over each chamber. TLG was
      calculated with a fixed threshold at SUV 2.5 (TLG2.5) and a relative threshold at
      42% of SUVmax (TLG42%). The histogram for each VOI was built and BSL was
      calculated. Comparison with the total injected FDG activity (TIA) was performed
      using concordance correlation coefficients (CCC) and the slope (a). Fifty
      consecutive patients with FDG-avid lung tumors were selected under an IRB waiver.
      TLG42%, TLG2.5 and BSL were compared to the reference standard calculating CCC
      and the slope. RESULTS: In both phantoms, the CCC for lesions with a TIA
      <=50ml*SUV between TIA and BSL was higher and the slope closer to 1 (CCC=0.933,
      a=1.189), than for TLG42% (CCC=0.350, a=0.731) or TLG2.5 (CCC=0.761, a=0.727). In
      50 lung lesions BSL had a slope closer to 1 compared to the reference activity
      than TLG42% (a=1.084 vs 0.618 - for high activity lesions) and also closer to 1
      than TLG2.5 (a=1.117 vs 0.548 - for low activity lesions). CONCLUSION: The
      histogram based BSL correlated better with TIA in both phantom studies than
      TLG2.5 or TLG42%. Also in lung tumors, the BSL activity is overall more accurate
      in quantifying the lesion activity compared to the two most commonly applied TLG
      quantification methods.

PMID- 24666720
TI  - Physical optimization of production by deuteron irradiation of high specific
      activity (177g)Lu suitable for radioimmunotherapy.
AB  - Deuteron-induced nuclear reactions for generation of no-carrier-added (NCA) Lu
      isotopes were investigated using the stacked-foil activation technique on natural
      Yb targets at energies up to Ed=18.18MeV. The decay curve of 177Yb, the growth
      curve of the cumulative (direct and indirect) and the direct production of
      (177g)Lu were determined. The analysis of these curves conducts to the evidence
      that the predominant route for the production of (177g)Lu is the indirect
      reaction 176Yb(d,p)177Yb, which decays to (177g)Lu. In the spectra acquired one
      year from the EOB the gamma lines of (177m)Lu are not evident. A comparison
      between the calculated activity of (177g)Lu produced with a cyclotron and with a
      nuclear reactor is given.

PMID- 24666721
TI  - Animal study assessing safety of an acoustic coupling fluid that holds the
      potential to avoid surgically induced artifacts in 3D ultrasound guided
      operations.
AB  - BACKGROUND: Use of ultrasound in brain tumor surgery is common. The difference in
      attenuation between brain and isotonic saline may cause artifacts that degrade
      the ultrasound images, potentially affecting resection grades and safety. Our
      research group has developed an acoustic coupling fluid that attenuates
      ultrasound energy like the normal brain. We aimed to test in animals if the newly
      developed acoustic coupling fluid may have harmful effects. METHODS: Eight rats
      were included for intraparenchymal injection into the brain, and if no adverse
      reactions were detected, 6 pigs were to be included with injection of the
      coupling fluid into the subarachnoid space. Animal behavior, EEG registrations,
      histopathology and immunohistochemistry were used in assessment. RESULTS: In
      total, 14 animals were included, 8 rats and 6 pigs. We did not detect any
      clinical adverse effects, seizure activity on EEG or histopathological signs of
      tissue damage. CONCLUSION: The novel acoustic coupling fluid intended for brain
      tumor surgery appears safe in rats and pigs under the tested circumstances.

PMID- 24666722
TI  - Job stress and job satisfaction among new graduate nurses during the first year
      of employment in Taiwan.
AB  - Nurse graduates are leaving their first employment at an alarming rate. The
      purpose of this study was to explore the relationships between job stress, job
      satisfaction and related factors over time among these nurses. This study applied
      a longitudinal design with three follow-ups after nurse graduates' first
      employment began. Using convenience sampling, participants were 206 new graduates
      from a university. The Work Environment Nursing Satisfaction Survey and the
      Clinical Stress Scale were used in this study. Results indicated that job stress
      remained moderate across three time points. Participants working 12 h shifts
      exhibited less job stress. Job satisfaction significantly increased in the
      twelfth month. Participants working 12 h shifts had a higher degree of job
      satisfaction. Job stress was negatively correlated with job satisfaction. The 12
      h work shifts were related to job stress and job satisfaction. These results
      implied that health-care administrators need to provide longer orientation
      periods and flexible shift schedules for new graduate nurses to adapt to their
      work environment. 

PMID- 24666723
TI  - Ketofol simulations for dosing in pediatric anesthesia.
AB  - BACKGROUND: Propofol mixed with racemic ketamine (or 'ketofol') is popular for
      short procedural sedation and analgesia. Use is creeping into anesthesia, yet
      neither the optimal combination nor infusion rate is known. The EC(50) of
      propofol's antiemetic effect is reported to be 0.343 mg.l(-1), while ketamine
      analgesia is thought to persist with concentrations above 0.2 mg.l(-1). We aimed
      to determine a ketofol dosing regimen for anesthesia 30-min and 1.5-h duration in
      a healthy child that did not unduly compromise recovery. METHODS: Pharmacokinetic
      pharmacodynamic parameters were used to simulate drug concentration and effect
      profiles over time for different ratios of propofol to ketamine ratios (1 : 1 to
      10 : 1) and rates. The target effect was the 95% probability of loss of response
      to a 5-s transcutaneous tetanus (P05). Combined effects were additive, with a
      propofol EC(50) of 3.1 mg.l(-1), ketamine EC(50) of 0.64 mg.l(-1), and slope of
      5.4. The time to predicted 50% probability of return of this response after
      ceasing infusion (P(50)) was determined for a 5-year-old 20-kg healthy child.
      RESULTS: The addition of ketamine to propofol infused using a manual infusion
      regimen (loading dose 3 mg.kg(-1), then 15 mg.kg(-1) .h(-1) for 15 min, 13 mg.kg(
      1) .h(-1) for 15 min, 11 mg.kg(-1) .h(-1) for 30 min, and 10 mg.kg(-1) .h(-1) for
      1-2 h) caused prolonged postoperative sedation. The P(50) after a 1.5-h infusion
      using a 1 : 1 mixture was 4.5 h, 2 : 1 mixture was 3.25 h, 5 : 1 mixture was 1.6
      h, and 10 : 1 mixture was 40 min. These P(50) estimates could be reduced by
      slowing administration infusion rates to 20%, 33%, 50%, 67%, 80%, and 90% for
      mixtures 1 : 1, 2 : 1, 3 : 1, 5 : 1, 6.7 : 1, and 10 : 1, respectively. These
      rates achieve a P(50) of approximately 20 min for 30-min duration anesthesia and
      60 min for 1.5-h duration anesthesia. CONCLUSIONS: The addition of ketamine to
      propofol infusion will prolong recovery unless infusion rates are decreased. We
      suggest an optimal ratio of racemic ketamine to propofol of 1 : 5 for 30-min
      anesthesia and 1 : 6.7 for 90-min anesthesia. Delivery of these ratios achieves
      propofol concentrations above an antiemetic threshold for longer than the
      ketamine concentration above the analgesic threshold during, potentially reducing
      postoperative nausea incidence.

PMID- 24666724
TI  - Transcriptional override: a regulatory network model of indirect responses to
      modulations in microRNA expression.
AB  - BACKGROUND: Documented changes in levels of microRNAs (miRNA) in a variety of
      diseases including cancer are leading to their development as early indicators of
      disease, and as a potential new class of therapeutic agents. A significant hurdle
      to the rational application of miRNAs as therapeutics is our current inability to
      reliably predict the range of molecular and cellular consequences of
      perturbations in the levels of specific miRNAs on targeted cells. While the
      direct gene (mRNA) targets of individual miRNAs can be computationally predicted
      with reasonable degrees of accuracy, reliable predictions of the indirect
      molecular effects of perturbations in miRNA levels remain a major challenge in
      molecular systems biology. RESULTS: Changes in gene (mRNA) and miRNA expression
      levels between normal precursor and ovarian cancer cells isolated from patient
      tissue samples were measured by microarray. Expression of 31 miRNAs was
      significantly elevated in the cancer samples. Consistent with previous reports,
      the expected decrease in expression of the mRNA targets of upregulated miRNAs was
      observed in only 20-30% of the cancer samples. We present and provide
      experimental support for a network model (The Transcriptional Override Model;
      TOM) to account for the unexpected regulatory consequences of modulations in the
      expression of miRNAs on expression levels of their target mRNAs in ovarian
      cancer. CONCLUSIONS: The direct and indirect regulatory effects of changes in
      miRNA expression levels in vivo are interactive and complex but amenable to
      systems level modeling. Although TOM has been developed and validated within the
      context of ovarian cancer, it may be applicable in other biological contexts as
      well, including of potential future use in the rational design of miRNA-based
      strategies for the treatment of cancers and other diseases.

PMID- 24666725
TI  - ICSH guidelines for the evaluation of blood cell analysers including those used
      for differential leucocyte and reticulocyte counting.
AB  - This revision is intended to update the 1994 ICSH guidelines. It is based on
      those guidelines but is updated to include new methods, such as digital image
      analysis for blood cells, a flow cytometric method intended to replace the
      reference manual 400 cell differential, and numerous new cell indices not
      identified morphologically are introduced. Haematology analysers are becoming
      increasingly complex and with technological advancements in instrumentation with
      more and more quantitative parameters are being reported in the complete blood
      count. It is imperative therefore that before an instrument is used for testing
      patient samples, it must undergo an evaluation by an organization or laboratory
      independent of the manufacturer. The evaluation should demonstrate the
      performance, advantages and limitations of instruments and methods. These
      evaluations may be performed by an accredited haematology laboratory where the
      results are published in a peer-reviewed journal and compared with the
      validations performed by the manufacturer. A less extensive
      validation/transference of the equipment or method should be performed by the
      local laboratory on instruments prior to reporting of results. 

PMID- 24666726
TI  - Brain metastasis from gastrointestinal cancers: a systematic review.
AB  - BACKGROUND: Brain metastases (BM) from the gastrointestinal tract (GIT) cancers
      are relatively rare. Despite those advances in diagnostic and treatment options,
      life expectancy and quality of life in these patients are still poor. In this
      review, we present an overview of the studies which have been previously
      performed as well as a comprehensive strategy for the assessment and treatment of
      BM from the GIT cancers. METHOD: To obtain information on brain metastases from
      GIT, we performed a systematic review of Medline, EMBASE and the Cochrane Central
      Register of Controlled Trials (CENTRAL). The collected data included patient
      characteristics, primary tumor data and brain metastases data. RESULT: In our
      search of the literature, we found 74 studies between 1980 and 2011, which
      included 2538 patients with brain metastases originated from gastrointestinal
      cancer. Analysis of available data showed that among 2538 patients who had brain
      metastases from GIT, a total of 116 patients (4.57%) had esophageal cancer, 148
      patients (5.83%) had gastric cancer, 233 patients (9.18%) had liver cancer, 13
      patients had pancreas cancer (0.52%) and 2028 patients (79.90%) had colorectal
      cancer. The total median age of the patients was 58.9 years. CONCLUSION: Brain
      metastases have been considered the most common structural neurological
      complication of systemic cancer. Due to poor prognosis they influence the
      survival rate as well as the quality of life of the patients. The treatment of
      cerebral metastasis depends on the patients' situation and the decisions of the
      treating physicians. The early awareness of a probable metastasis from GI to the
      brain will have a great influence on treatment outcomes as well as the survival
      rate and the quality-of-life of the patients.

PMID- 24666727
TI  - Chondrosarcoma presenting with pulmonary embolism in a 9-year-old girl: a case
      report.
AB  - Chondrosarcoma is a malignant bone tumour common in adults, third to myeloma and
      osteosarcoma, but is exceptionally rare in children. Here we discuss a 9-year-old
      girl presenting with occlusive right pulmonary artery neoplastic embolus,
      resulting from a primary right proximal humerus chondrosarcoma. To the best of
      our knowledge, this the first pediatric and only second overall case reported in
      the United States of a neoplastic pulmonary embolus resulting from a primary
      chondrosarcoma. 

PMID- 24666729
TI  - Perceptual effects and efficacy of intermittent or continuous blood flow
      restriction resistance training.
AB  - Blood flow restriction (BFR) exercise may be an alternative form of resistance
      training; however, a side of effect of BFR resistance exercise is acute muscle
      pain. Typically, BFR exercise studies restrict blood flow with a cuff
      continuously during the exercise bout, including rest periods. However, others
      have used intermittent BFR where the cuff is inflated only during sets. We
      performed two studies to compare intermittent and continuous BFR exercise. In
      study one, eleven subjects randomly proceeded through three treatments of
      unilateral leg extensions to failure: (i) continuous BFR, (ii) intermittent BFR
      and (iii) control (exercise without BFR). Pain measurements were taken
      immediately after each set. In study two, subjects (n = 32) underwent a 5-week
      resistance training programme after random assignment to one of the three
      conditions. Lean mass and strength were assessed at baseline and after training.
      Continuous BFR resulted in significantly greater pain than intermittent BFR or
      control. Both BFR conditions resulted in significantly fewer repetitions to
      failure than control. This suggests that an acute bout of intermittent BFR
      exercise may produce as much muscle fatigue as an acute bout of continuous BFR
      exercise, but with less pain. With training, maximal knee extension (P = 0.033)
      and maximum knee flexion (P = 0.007) strength increased among all groups. There
      were no significant differences between groups in strength or lean mass. These
      results suggest that short-term low-load resistance training increases muscle
      strength to a similar extent as low-load resistance training without BFR.

PMID- 24666728
TI  - Detection of hepatocellular carcinoma in hepatitis C patients: biomarker
      discovery by LC-MS.
AB  - Hepatocellular carcinoma (HCC) accounts for most cases of liver cancer worldwide;
      contraction of hepatitis C (HCV) is considered a major risk factor for liver
      cancer even when individuals have not developed formal cirrhosis. Global,
      untargeted metabolic profiling methods were applied to serum samples from
      patients with either HCV alone or HCC (with underlying HCV). The main objective
      of the study was to identify metabolite based biomarkers associated with cancer
      risk, with the long term goal of ultimately improving early detection and
      prognosis. Serum global metabolite profiles from patients with HCC (n=37) and HCV
      (n=21) were obtained using high performance liquid chromatography-mass
      spectrometry (HPLC-MS) methods. The selection of statistically significant
      metabolites for partial least-squares discriminant analysis (PLS-DA) model
      creation based on biological and statistical significance was contrasted to that
      of a traditional approach utilizing p-values alone. A PLS-DA model created using
      the former approach resulted in a model with 92% sensitivity, 95% specificity,
      and an AUROC of 0.93. A series of PLS-DA models iteratively utilizing three to
      seven metabolites that were altered significantly (p<0.05) and sufficiently
      (FC<=0.7 or FC>=1.3) showed good performance using p-values alone; the best of
      these PLS-DA models was capable of generating 73% sensitivity, 95% specificity,
      and an AUROC of 0.92. Metabolic profiles derived from LC-MS readily distinguish
      patients with HCC and HCV from those with HCV only. Differences in the metabolic
      profiles between high-risk individuals and HCC indicate the possibility of
      identifying the early development of liver cancer in at risk patients. The use of
      biological significance as a selection process prior to PLS-DA modeling may offer
      improved probabilities for translation of newly discovered biomarkers to clinical
      application. 

PMID- 24666730
TI  - A mock juror investigation of blame attribution in the punishment of hate crime
      perpetrators.
AB  - We examined blame attribution as a moderator of perceptions of hate crimes
      against gay, African American, and transgender victims. Participants were 510
      Texas jury panel members. Results of vignette-based crime scenarios showed that
      victim blame displayed significant negative, and perpetrator blame significant
      positive, effects on sentencing recommendations. Also as hypothesized, victim and
      perpetrator blame moderated the effect of support for hate crime legislation.
      Interaction patterns suggested that both types of blame attribution influence
      sentencing recommendations, but only for participants disagreeing with hate crime
      legislation. Three-way interactions with victim type also emerged, indicating
      that the effects of both types of blame attribution show particular influences
      when the victim is gay, as opposed to transgender or African American.
      Implications for attribution theory, hate crime policy, and jury selection are
      discussed.

PMID- 24666732
TI  - Workplace harassment: a test of definitional criteria derived from an analysis of
      research definitions and Canadian social definitions.
AB  - Public awareness of the occurrence and effects of workplace harassment continues
      to grow. However, despite increasing awareness, ambiguity remains about how
      harassment is defined and, consequently, how to determine whether a questionable
      situation should be judged as harassment. For this research we reviewed
      definitions of workplace harassment and identified four elements that were
      frequently included as criteria for making judgments of whether harassment had
      occurred (i.e., repetition, intent, perceived intent, consequences). In two
      separate studies, fictional scenarios were used to evaluate the extent to which
      participants' judgments about harassment were affected by the presence or absence
      of the four elements. Ratings of the scenarios provided by student participants
      (study one; N=160) and a convenience sample of community participants (study two;
      N=292) with varying levels of work experience and diverse professional
      backgrounds were analysed. According to our results the four elements
      significantly influenced participants' judgments of harassment. The intent of the
      harasser had the strongest and most consistent effect on harassment judgements
      and whether the behaviour was repeated had the weakest and least consistent
      effect. In addition to the unique effects of the individual elements, significant
      interactions between the elements emerged and suggest that harassment judgements
      depend on the interplay of a variety of factors. Though the results of these
      studies add to the growing body of research that focuses on defining workplace
      harassment, they also highlight the need for additional research in the area.

PMID- 24666733
TI  - Social support among releasing men prisoners with lifetime trauma experiences.
AB  - High rates of lifetime trauma experiences exist among men incarcerated in US
      state and federal prisons. Because lifetime trauma experiences have been linked
      to problematic behavioral and psychiatric outcomes for incarcerated populations,
      trauma-informed interventions could improve post-release well-being of releasing
      men prisoners with trauma histories. Social support has consistently been found
      to have a positive impact on trauma-related outcomes in non-incarcerated
      populations. Therefore, it is reasonable to hypothesize that social support may
      be an important intervention component for releasing men prisoners with trauma
      experiences; yet, the relationship between trauma experiences, psychiatric and
      behavioral factors, and social support has received almost no attention in
      research with men prisoners. Using a probability sample of 165 soon-to-be
      released men, the present study examined differences in certain demographic,
      criminal justice history, mental health, substance abuse, and social support
      (type, quality, amount, and source) variables between releasing men prisoners
      with and without lifetime trauma experiences. Results indicate that men with
      trauma histories had more negative social support experiences and fewer positive
      social support resources before prison than their counterparts. Men with trauma
      histories also had more lifetime experiences with mental health and substance use
      problems. On further investigation of the subsample of men with trauma histories,
      those who were older, had substance use disorders, and histories of mental health
      problems anticipated fewer post-release social support resources. Study findings
      underscore the nuances of social support for men prisoners with trauma
      experiences and point to implications for future directions in targeted trauma
      informed intervention development for releasing men prisoners. 

PMID- 24666731
TI  - Envisioning the next generation of behavioral health and criminal justice
      interventions.
AB  - The purpose of this paper is to cast a vision for the next generation of
      behavioral health and criminal justice interventions for persons with serious
      mental illnesses in the criminal justice system. The limitations of first
      generation interventions, including their primary focus on mental health
      treatment connection, are discussed. A person-place framework for understanding
      the complex factors that contribute to criminal justice involvement for this
      population is presented. We discuss practice and research recommendations for
      building more effective interventions to address both criminal justice and mental
      health outcomes. 

PMID- 24666734
TI  - Goats excel at learning and remembering a highly novel cognitive task.
AB  - INTRODUCTION: The computational demands of sociality (maintaining group cohesion,
      reducing conflict) and ecological problems (extractive foraging, memorizing
      resource locations) are the main drivers proposed to explain the evolution
      cognition. Different predictions follow, about whether animals would
      preferentially learn new tasks socially or not, but the prevalent view today is
      that intelligent species should excel at social learning. However, the
      predictions were originally used to explain primate cognition, and studies of
      species with relatively smaller brains are rare. By contrast, domestication has
      often led to a decrease in brain size, which could affect cognition. In domestic
      animals, the relaxed selection pressures compared to a wild environment could
      have led to reduced social and physical cognition. Goats possess several features
      commonly associated with advanced cognition, such as successful colonization of
      new environments and complex fission-fusion societies. Here, we assessed goat
      social and physical cognition as well as long-term memory of a complex two-step
      foraging task (food box cognitive challenge), in order to investigate some of the
      main selection pressures thought to affect the evolution of ungulate cognition.
      RESULTS: The majority of trained goats (9/12) successfully learned the task
      quickly; on average, within 12 trials. After intervals of up to 10 months, they
      solved the task within two minutes, indicating excellent long-term memory. The
      goats did not learn the task faster after observing a demonstrator than if they
      did not have that opportunity. This indicates that they learned through
      individual rather than social learning. CONCLUSIONS: The individual learning
      abilities and long-term memory of goats highlighted in our study suggest that
      domestication has not affected goat physical cognition. However, these cognitive
      abilities contrast with the apparent lack of social learning, suggesting that
      relatively intelligent species do not always preferentially learn socially. We
      propose that goat cognition, and maybe more generally ungulate cognition, is
      mainly driven by the need to forage efficiently in harsh environments and feed on
      plants that are difficult to access and to process, more than by the
      computational demands of sociality. Our results could also explain why goats are
      so successful at colonizing new environments.

PMID- 24666735
TI  - Varying ethics rules in clinical research and routine patient care--research
      ethics committee chairpersons' views in Finland.
AB  - BACKGROUND: To present empirical data on how the variation in regulating clinical
      research and patient care was perceived in Finland between 2009 and 2012.
      METHODS: Notes of interviews with 22 research ethics committee (REC) chairpersons
      were analyzed to identify whether differences in the regulation of clinical
      research and patient care were addressed. REC chairpersons' opinions on three
      imaginary cases of clinical research projects challenging current research ethics
      rules (vignettes) were requested with a questionnaire; 18 of the 22 interviewed
      chairpersons responded. RESULTS: Based on REC chairpersons' interviews, the
      differences between care and research regulation were not considered important
      issues in Finland. In the vignettes, REC chairpersons' assumptions on how their
      REC would decide varied in regard to allowing research without informed consent,
      while solutions that are not allowed by current law were even anticipated.
      Mostly, but not always, the chairpersons' own personal view agreed with their
      REC. CONCLUSIONS: The distinction between care and research regulation has not
      been publicly challenged by Finnish RECs, even though it is a challenge when
      research relevant to health care is carried out. There is a need for debate and
      changes in laws and practices.

PMID- 24666737
TI  - Reconfirmation of endotracheal tube depth after clinical method.

PMID- 24666736
TI  - CNX-011-67, a novel GPR40 agonist, enhances glucose responsiveness, insulin
      secretion and islet insulin content in n-STZ rats and in islets from type 2
      diabetic patients.
AB  - BACKGROUND: GPR40 is a G-protein coupled receptor regulating free fatty acid
      induced and also glucose induced insulin secretion. We generated neonatally
      streptozotocin-treated female rats (n-STZ) and treated them with CNX-011-67, a
      GPR40 agonist to examine the role of GPR40 in modulation of glucose metabolism,
      insulin secretion and content. METHODS: Female n-STZ animals were orally
      administered with CNX-011-67 (15 mg/kg body weight, twice daily) or with vehicle
      for 8 weeks (n = 8 per group). Glucose tolerance in treated animals and insulin
      secretion, islet insulin content and gene expression in isolated islets were
      determined. Islets from type 2 diabetic mellitus (T2DM) patients were treated
      with different concentrations of glucose in presence or absence of CNX-011-67 and
      insulin secretion was measured. RESULTS: Treatment of n-STZ rats with GPR40
      agonist CNX-011-67 enhanced insulin secretion in response to oral glucose load on
      day 0 and this response persisted during the treatment period. The treatment also
      produced a 'memory effect' during which insulin secretion in response to oral
      glucose load remained enhanced, for a week, even in absence of the agonist.
      Activation of GPR40 enhanced responsiveness of islets to glucose and increased
      glucose induced insulin secretion and islet insulin content. An increase in islet
      mRNA expression of GCK, PDX1, insulin and PC was also observed. Acute treatment
      of islets from n-STZ rats with GPR40 agonist enhanced cellular ATP content.
      Activation of GPR40 enhanced mitochondrial calcium level in NIT-1 insulinoma
      cells. CNX-011-67 increased insulin secretion in islets from T2DM patients which
      were non-responsive to increased glucose concentration CONCLUSIONS: Our data
      provide evidence that activation of GPR40 with CNX-011-67 stimulates glucose
      metabolism, enhances glucose responsiveness, increases insulin secretion and
      content and that pharmacological activation of GPR40 will prove beneficial for
      treatment of T2DM.

PMID- 24666738
TI  - Life-threatening bleeding from gastrointestinal stromal tumor: successful
      embolization with subsequent laparoscopic surgery.

PMID- 24666739
TI  - Risk screening for long QT prior to prescribing levofloxacin.

PMID- 24666740
TI  - Mechanical factors affecting nebulized albuterol aerosol particle sizes for
      asthma drug delivery.
AB  - BACKGROUND: Nebulized particles must have diameters between 1 to 5 MUm (optimal
      particle size range [OPSR]) to be deposited in the lower respiratory tract. The
      purpose of this study is to determine factors that affect the particle size
      distributions of nebulized albuterol. METHODS: We used a sophisticated laser
      diffraction machine to measure aerosol particle size distributions. We compared
      the percentage of particles in the OPSR at different flow rates through single
      use disposable (SUD) and semipermanent nebulizers at different flow rates under
      different conditions. RESULTS: The SUD nebulizer produced OPSR percentages of
      16%, 28%, 40%, 50%, 56%, and 62% at 3, 4, 5, 6, 7, and 8 Liters per minute (Lpm),
      respectively. The semipermanent nebulizer, however, produced OPSR percentages of
      57%, 57%, 60%, and 64% at 3, 4, 5, and 6 Lpm, respectively. The home pump
      produced a gas flow rate of 5.2 Lpm through the SUD nebulizer and 4.2 Lpm through
      the semipermanent nebulizer. Single-use disposable nebulizer performance did not
      degrade with use up to 150 nebulizations. Optimal particle size range percentages
      did not change significantly with large or small nebulization volumes.
      CONCLUSION: Single-use disposable nebulizers do not degrade with use, but their
      performance is highly dependent on gas flow rates. At the flow rate achieved by
      the home pump, the semipermanent nebulizer performs better than the SUD
      nebulizer.

PMID- 24666741
TI  - Intra-abdominal injury is easily overlooked in the patients with concomitant
      unstable hemodynamics and pelvic fractures.
AB  - INTRODUCTION: Transcatheter arterial embolization (TAE) is usually necessary in
      the management of hemodynamically unstable patients with concomitant pelvic
      fractures. Given the critical conditions of such patients, TAE is at times
      performed only according to the results of a primary evaluation without computed
      tomographic (CT) imaging. Therefore, the evaluation of associated intra-abdominal
      injuries (IAIs) might be insufficient. Clinically, some patients have required
      post-TAE laparotomy due to further deterioration. In this study, we attempted to
      determine a feasible protocol for post-TAE observation. MATERIALS AND METHODS:
      This study focused on patients who received TAE to achieve hemostasis of
      retroperitoneal hemorrhage and who did not undergo CT imaging due to their
      unstable hemodynamics. The characteristics of patients with and without
      associated IAIs requiring post-TAE laparotomy were compared. We also analyzed the
      effects of the timing of post-TAE CT imaging on patients with IAIs requiring
      surgery. RESULTS: A total of 41 patients were enrolled in the study. Of these
      patients, all of whom underwent primary TAE without preprocedure CT imaging; 15
      patients (15/41, 36.6%) required post-TAE laparotomy due to further
      deterioration. Comparisons between the 2 patient groups revealed no significant
      differences in the rate of endotracheal intubation (80.0% vs 65.4%, P=.480), loss
      of consciousness (66.7% vs 73.1%, P=.730), or abdominal symptoms (20.0% vs 23.1%,
      P=1.000). CONCLUSION: In the management of hemodynamically unstable patients with
      concomitant pelvic fractures, greater attention should be paid to associated
      IAIs. Early CT imaging is encouraged after the patient's hemodynamic status is
      stabilized with TAE.

PMID- 24666742
TI  - Heatstroke model for desert dry-heat environment and observed organ damage.
AB  - BACKGROUND: Heatstroke is one of the most common clinical emergencies. Heatstroke
      that occurred in a dry-heat environment such as desert is usually more seriously
      effective and often leads to death. However, the report of the pathophysiologic
      mechanisms about heatstroke in dry-heat environment of desert has not been seen.
      OBJECTIVES: Our objectives are to establish a rat model of heatstroke of dry-heat
      environment of desert, to assess the different degrees of damage of organ, and to
      preliminarily discuss the mechanism of heatstroke in dry-heat environment of
      desert. METHODS: The first step, we have established a rat heatstroke model of
      dry heat environment of desert. The second step, we have accessed changes in
      morphology and blood indicators of heatstroke rats in dry-heat environment of
      desert. RESULTS: The heatstroke rats have expressed the changing characteristics
      of mean arterial pressure, core temperature, and heart rate. The organ damage
      changed from mild to serious level, specifically in the morphology and blood
      enzymology parameters such as alanine aminotransferase, aspartate
      aminotransferase, creatinine, urea, uric acid, creatine kinase-MB, creatine
      kinase, and blood gas parameters such as base excess extracellular fluid and
      bicarbonate ions (HCO3-). CONCLUSIONS: We have successfully established the rat
      heatstroke model of dry-heat environment of desert. We have identified heatstroke
      rats that presented changing characteristics on physiological indicators and
      varying degrees of organ damage, which are aggravated by the evolution of
      heatstroke in dry-heat environment of desert. We have preliminarily discussed the
      mechanism of heatstroke in dry-heat environment of desert.

PMID- 24666743
TI  - Towards a less invasive approach to the early goal-directed treatment of septic
      shock in the ED.
AB  - INTRODUCTION: Early goal-directed therapy (EGDT) in septic shock defined by
      Rivers et al was proven to reduce mortality and validated by observational
      studies. However, criticism is centered in particular on the early requirement of
      a central venous catheter (CVC) and on central venous pressure (CVP) as an
      indicator of volume responsiveness. The present study is a pivotal study to
      investigate the reliability of a less invasive approach, which uses inferior vena
      cava (IVC) and lung ultrasounds (US) to guide the infusion of fluids and lactate
      clearance to monitor tissue perfusion. METHODS: We enrolled 51 patients with
      septic shock. As a marker of preload optimization, we measured IVC collapse in
      place of CVP and serum lactate clearance in place of central venous oxygen
      saturation as a marker of tissue perfusion. As outcomes, we considered the
      accomplishment of the noninvasive EGDT goals, the number of patients treated
      without the need of a CVC, the amount of fluids administered in the first 6
      hours, the development of pulmonary edema, and the overall mortality rate.
      RESULTS: Inferior vena cava US evaluation resulted feasible in 92% of patients.
      Lung US was performed in 100% of cases. In the first 6 hours, only 61.7% of
      patients received a CVC, an average of 5.5 L of crystalloids were administered,
      and only 4 patients developed clinical overt pulmonary edema. Mortality was 34%
      at 28 days and 38.3% at 60 days. CONCLUSIONS: Our approach to resuscitation in
      septic shock appears feasible in the emergency department and needs further study
      with a randomized controlled trial.

PMID- 24666744
TI  - Retrospective analysis of clinical data associated with patients enrolled in a
      molecular diagnostic feasibility study highlights the potential utility for rapid
      detection of bloodstream infection.
AB  - BACKGROUND: Measurement of pathogen DNA polymerase activity by enzymatic template
      generation and amplification (ETGA) has shown promise in detecting pathogens in
      bloodstream infection (BSI). We perform an in-depth analysis of patients with
      clinical BSI enrolled in ETGA feasibility experiments. METHODS: In addition to
      hospital blood cultures, 1 study aerobic culture bottle was drawn from patients
      with suspected BSI. The study bottle was split into 2 bottles and was
      additionally subjected to ETGA analysis. Enzymatic template generation and
      amplification sensitivity/specificity for BSI detection was determined against
      the Centers for Disease Control BSI definition. When split cultures were both
      positive, time course analysis was performed to determine time to detection. The
      records of patients with BSI were reviewed for presence of systemic inflammatory
      response syndrome, antibiotic timing and appropriateness, and organism
      identification. RESULTS: Of 307 enrollees, 38 met the Centers for Disease Control
      BSI definition. Seventy-four percent met systemic inflammatory response syndrome
      criteria on admission. Antibiotic coverage was adequate in 76% of patients.
      Antibiotics were more often delayed in afebrile patients (odds ratio, 5). Twenty
      seven of the split study culture bottles were positive in at least 1 sample, and
      ETGA detected microbes within all samples (sensitivity/specificity, 70.3%/99.3%).
      Of these, 22 were culture positive in both split study bottles and underwent ETGA
      time course analysis. Enzymatic template generation and amplification detected
      microbes within these 3-fold faster than culture. CONCLUSIONS: Patients with BSI
      often have diagnostic and treatment delays. Enzymatic template generation and
      amplification provides clinically meaningful data more rapidly than cultures.
      Future development should focus on real-time application of assays that detect
      microbes at the molecular level.

PMID- 24666745
TI  - An unusual complication of cardiopulmonary resuscitation: stomach perforation.

PMID- 24666746
TI  - Rescue of the limb after accidental injection of diazepam into femoral artery.

PMID- 24666747
TI  - Cost Utility Analysis of Percutaneous Adhesiolysis in Managing Pain of Post
      lumbar Surgery Syndrome and Lumbar Central Spinal Stenosis.
AB  - BACKGROUND: The increase in the number of interventions for the management of
      chronic pain and associated escalation of healthcare costs has captured the
      attention of health policymakers, in no small part due to the lack of
      documentation of efficacy, cost-effectiveness, or cost utility analysis. A recent
      cost utility analysis of caudal epidural injections in managing chronic low back
      pain of various pathologies showed a high cost utility with improvement in
      quality of life years, competitive with various other modalities of treatments.
      However, there are no analyses derived from high-quality controlled studies
      related to the cost utility of percutaneous adhesiolysis in the treatment of post
      lumbar surgery syndrome or lumbar central spinal stenosis. STUDY DESIGN: This
      analysis is based on 2 previously published controlled studies. OBJECTIVE: To
      assess the cost utility of percutaneous adhesiolysis procedures in managing
      chronic low back and lower extremity pain secondary to post-lumbar surgery
      syndrome and lumbar central spinal stenosis. SETTING: A private, specialty
      referral interventional pain management center in the United States. METHODS: Two
      controlled studies were conducted assessing the clinical effectiveness of
      percutaneous adhesiolysis for post-lumbar surgery syndrome and lumbar central
      spinal stenosis in an interventional pain management setting utilizing
      contemporary interventional pain management practices. A cost utility analysis
      was performed with direct payment data for a total of 130 patients in treatment
      groups over a 2-year period. Various outcome measures were included with
      significant improvement, defined as at least 50% improvement with reduction in
      pain and disability status. RESULTS: The results of 2 controlled studies of low
      back pain with 60 and 70 patients and a 2-year follow-up with the actual
      reimbursement data showed cost utility for 1 year of quality-adjusted life year
      (QALY) of USD $2,652 for post-lumbar surgery syndrome and USD $2,649 for lumbar
      central spinal stenosis. The results of this assessment show that the cost
      utility of managing chronic, intractable low back pain with percutaneous
      adhesiolysis at a QALY that is similar or lower in price than medical therapy
      only, physical therapy, manipulation, spinal cord stimulation, and surgery.
      LIMITATIONS: The limitations of this cost utility analysis are that it is a
      single-center evaluation, with the inclusion of costs of adhesiolysis procedures
      in an ambulatory surgery center and physician visits, rather than all related
      costs including drug therapy and costs of disability in multiple settings.
      CONCLUSION: This cost utility analysis of percutaneous adhesiolysis in the
      treatment of post-lumbar surgery syndrome and lumbar central spinal stenosis
      shows the clinical effectiveness and cost utility of these procedures at USD
      $2,650 per one year of QALY when performed in an ambulatory surgery center.

PMID- 24666748
TI  - Needs of Aboriginal Australian women with comorbid mental and alcohol and other
      drug use disorders.
AB  - INTRODUCTION AND AIMS: Aboriginal Australian women have an important role in
      raising strong families. Yet there are many challenges for women with mental
      health disorders, sometimes following past traumas. This study examines
      experiences of Aboriginal women engaging with treatment services for co-occurring
      mental health and substance use disorders (SUD), and the experiences of their
      family, and of health staff seeking to support them. DESIGN AND METHODS: The
      study was implemented by four Aboriginal Community Controlled Health Services in
      urban and regional New South Wales to inform improvements to local health service
      delivery. All Aboriginal female clients with a diagnosed comorbid mental health
      and SUD were offered study participation by staff of that Aboriginal Medical
      Service. Semi-structured interviews were conducted by an independent Aboriginal
      interviewer: 21 with clients, 12 with adult family members of these clients and
      11 with Aboriginal health workers from these services. RESULTS: Clients (aged 21
      60) experienced a range of mental health and SUD, attributed by them to negative
      events early in life. Clients and family members reported that the disorders have
      severe impacts on the women and their families, including children. Considerable
      barriers to accessing relevant services were described. Suggested service
      improvements included more local inpatient treatment options, more friendly and
      flexible services, better service promotion and improved staff professional
      development opportunities. DISCUSSION AND CONCLUSION: Barriers to accessing
      mental health and SUD treatment (Aboriginal and mainstream) need addressing.
      Research is needed to optimise treatment to meet the complex needs of Aboriginal
      Australians with co-occurring mental health and SUD.

PMID- 24666749
TI  - RNA-seq analysis identifies an intricate regulatory network controlling cluster
      root development in white lupin.
AB  - BACKGROUND: Highly adapted plant species are able to alter their root
      architecture to improve nutrient uptake and thrive in environments with limited
      nutrient supply. Cluster roots (CRs) are specialised structures of dense lateral
      roots formed by several plant species for the effective mining of nutrient rich
      soil patches through a combination of increased surface area and exudation of
      carboxylates. White lupin is becoming a model-species allowing for the discovery
      of gene networks involved in CR development. A greater understanding of the
      underlying molecular mechanisms driving these developmental processes is
      important for the generation of smarter plants for a world with diminishing
      resources to improve food security. RESULTS: RNA-seq analyses for three
      developmental stages of the CR formed under phosphorus-limited conditions and two
      of non-cluster roots have been performed for white lupin. In total 133,045,174
      high-quality paired-end reads were used for a de novo assembly of the root
      transcriptome and merged with LAGI01 (Lupinus albus gene index) to generate an
      improved LAGI02 with 65,097 functionally annotated contigs. This was followed by
      comparative gene expression analysis. We show marked differences in the
      transcriptional response across the various cluster root stages to adjust to
      phosphate limitation by increasing uptake capacity and adjusting metabolic
      pathways. Several transcription factors such as PLT, SCR, PHB, PHV or AUX/IAA
      with a known role in the control of meristem activity and developmental processes
      show an increased expression in the tip of the CR. Genes involved in hormonal
      responses (PIN, LAX, YUC) and cell cycle control (CYCA/B, CDK) are also
      differentially expressed. In addition, we identify primary transcripts of miRNAs
      with established function in the root meristem. CONCLUSIONS: Our gene expression
      analysis shows an intricate network of transcription factors and plant hormones
      controlling CR initiation and formation. In addition, functional differences
      between the different CR developmental stages in the acclimation to phosphorus
      starvation have been identified.

PMID- 24666751
TI  - A case of ecological specialization in ladybirds: Iberorhyzobius rondensis
      (Coleoptera: Coccinellidae), potential biocontrol agent of Matsucoccus feytaudi
      (Hemiptera: Matsucoccidae).
AB  - Specialization is an important attribute of a biological control agent. The
      maritime pine bast scale, Matsucoccus feytaudi Ducasse (Hemiptera Matsucoccidae),
      is an invasive species in Southeast France and the North of Italy. Iberorhyzobius
      rondensis Eizaguirre (Coleoptera: Coccinellidae), is a recently described
      ladybird species. Both adults and larvae are predaceous, feeding on egg masses of
      M. feytaudi, and are strongly attracted to M. feytaudi's sex pheromone. To
      evaluate the potential of I. rondensis as a biocontrol agent of the scale, we
      studied its niche breadth and prey range with emphasis on pine forests and
      hemipterans as tested prey. In this study, I. rondensis was found to achieve
      complete development only when fed on M. feytaudi egg masses (92.9% survival) and
      an artificial prey: eggs of Ephestia kuehniella Zeller (27.6% survival). From the
      2nd instar onwards, complete development could be achieved using other prey
      species, although larvae had significantly higher mortality and slower
      development. In choice tests, M. feytaudi was the preferred prey. Surveys of the
      ladybird populations in the Iberian Peninsula revealed that it was found
      exclusively on Pinus pinaster Aiton, the sole host of M. feytaudi. The unusual
      specialization of I. rondensis, among other predaceous ladybirds, makes it an
      appropriate candidate for classical biological control of M. feytaudi. 

PMID- 24666750
TI  - Risk factors for eczema in infants born in Cuba: a population-based cross
      sectional study.
AB  - BACKGROUND: There is a concern that allergic disease in childhood is higher than
      expected in Cuba. The aim of this study was to determine the risk factors for
      eczema of infants aged 12-15 months living in Havana. METHODS: We used a cross
      sectional epidemiological study design. Data on eczema symptoms and a wide range
      of lifestyle factors were collected by researcher administered questionnaires.
      RESULTS: Data were collected on 1956 children (96% response rate), of whom 672
      (34%) were reported as having had eczema. Independent risk factors for eczema
      included young maternal age (adjusted odds ratio (OR) 0.98 per additional year of
      age; 95% confidence interval (CI) 0.97-0.99), child's weight (OR 1.13 per
      additional kg; 95% CI: 1.03-1.25), insect sting allergy (OR 2.11; 95% CI: 1.33
      3.35), rodents in the home (OR 1.39; 95% CI: 1.10-1.76), attendance at childcare
      facilities (OR 1.34: 95% CI: 1.05-1.70) and self-reported mould in the home (OR
      1.23; 95% CI: 1.07-1.41). Infant exposure to paracetamol was associated with an
      increased risk of eczema even after adjustment for wheeze (OR 1.22; 95% CI: 1.03
      1.46). CONCLUSION: Despite a very different culture and environment, the
      consistency of these findings with those from more economically developed
      countries suggests potential causal associations. The association with
      paracetamol, even after adjustment for wheeze, suggests that intervention studies
      are required in young infants, to ascertain if this commonly used anti-pyretic
      medication increases allergic disease.

PMID- 24666752
TI  - Metabolic profile of the different phenotypes of polycystic ovary syndrome in two
      Latin American populations.
AB  - OBJECTIVE: To evaluate the metabolic profile of Chilean and Argentinian women
      with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria.
      DESIGN: Observational cross-sectional study. SETTING: Academic centers.
      PATIENT(S): Women with PCOS, aged 18-39 years: 220 Chilean (PCOSCh) and 206
      Argentinian (PCOSAr). INTERVENTION(S): Physical examination, fasting blood
      samples for androgens, gonadotropins, metabolic parameters, and a transvaginal
      ultrasound. MAIN OUTCOME MEASURE(S): Comparative analysis of the metabolic
      profile in both populations divided into four phenotypes. RESULT(S): The
      distribution of the different phenotypes was different in both populations.
      PCOSCh women showed a higher body mass index and a higher percentage of metabolic
      syndrome in all phenotypes compared with the PCOSAr women. The PCOSAr women
      exhibited a statistically significantly higher diastolic blood pressure in
      phenotypes A, B, and C and a higher percentage of hypertension in phenotypes A
      and D compared with the PCOSCh women. CONCLUSION(S): The data show differences in
      the metabolic profile of both populations. PCOSCh women presented with greater
      metabolic alterations such as dysglycemia and dyslipidemia and a higher
      prevalence of metabolic syndrome, independent of the phenotype. The PCOSAr
      patients showed more elevated blood pressure. Ethnic diversity associated with
      environmental factors are fundamental elements in the analysis of the PCOS
      phenotypes.

PMID- 24666753
TI  - The influence of prior oral contraceptive use on risk of endometriosis is
      conditional on parity.
AB  - OBJECTIVE: To estimate the influence of prior oral contraceptive pill (OCP) use
      on future diagnosis of endometriosis in young women. DESIGN: Prospective cohort
      study, the Australian Longitudinal Study on Women's Health. SETTING: Community
      based sample. PATIENT(S): 9,585 women age 18-23 at study onset. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Risk of self-reported endometriosis estimated with
      Cox proportional-hazards regression with time-dependent covariates. RESULT(S):
      Compared with never users, endometriosis hazard ratios in nulliparous women with
      <5 years and >= 5 years of OCP use (preceding diagnosis) were 1.8 (95% CI, 1.30
      2.53) and 2.3 (95% CI, 1.59-3.40), respectively. Similar risk was seen in both
      women reporting infertility and unsure fertility. In parous women with <5 years
      of use, the hazard ratio for endometriosis was 0.41 (95% CI, 0.15-0.56) and for
      >= 5 years of use was 0.45 (95% CI, 0.16-1.23). Women reporting early
      noncontraceptive OCP use had a twofold higher risk (odds ratio 2.07; 95% CI, 1.72
      2.51). CONCLUSION(S): Prior OCP exposure reduces the risk of diagnosis of
      endometriosis in parous women but increases it among nulliparous women; these
      associations appear unaffected by fertility status. An increased risk of
      endometriosis diagnosis seen in women reporting early noncontraceptive OCP use
      may explain some of the positive OCP risk seen in nulliparous women.

PMID- 24666754
TI  - Human chorionic gonadotropin discriminatory zone in ectopic pregnancy: does assay
      harmonization matter?
AB  - OBJECTIVE: To determine the effect that lack of hCG assay harmonization has on
      the interpretation of a serum hCG concentration with regards to the hCG
      discriminatory zone. DESIGN: A multisite method comparison study. SETTING:
      Clinical laboratories. PATIENT(S): Eighty serum samples containing various
      concentrations of hCG. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Concentrations of hCG obtained from seven hCG reagent platforms. RESULT(S): The
      hCG concentrations were significantly different across hCG reagent platforms.
      Seventy-one percent of assay pairs showed significant differences with samples
      selected based on hCG concentrations between 1,500 and 3,500 IU/L as determined
      by a comparative method. Relative to the comparative method, the calculated hCG
      discriminatory zones for five assays were within 9%, and one assay was within 40%
      of the target concentrations of 1,500 and 3,500 IU/L. CONCLUSION(S): Despite
      significant differences in hCG concentrations across hCG immunoassays, an hCG
      concentration within a discriminatory zone of 1,500-3,500 IU/L can be used for
      all but one commonly used hCG reagent platform.

PMID- 24666755
TI  - Risk factors for early miscarriage among Chinese: a hospital-based case-control
      study.
AB  - OBJECTIVE: To investigate the risk factors for early miscarriage among Chinese
      women. DESIGN: Hospital-based matched case-control study. SETTING: Academic
      medical center and maternal health hospital. PATIENT(S): 620 women with early
      miscarriage (less than 13 weeks of gestation) and 1,240 normal pregnant women.
      INTERVENTION(S): Face-to-face questionnaire. MAIN OUTCOME MEASURE(S):
      Multivariable conditional odds ratio (OR) and 95% confidence interval (CI) to
      measure risk factors. RESULT(S): After adjustment for confounding factors, the
      following were independently associated with increased risk: history of
      miscarriage, repeated induced abortion, working night shifts, and frequent
      staying up late. Vitamin supplementation and regular physical activity reduced
      the risk of miscarriage. We did not find paternal age, alcohol consumption, or
      smoking status to be linked with early miscarriage. CONCLUSION(S): Our findings
      suggest that a healthy diet, regular physical activity, and planned pregnancy may
      be advantageous for women in pre-pregnancy or early pregnancy. Induced abortion,
      working night shifts, and frequent staying up late were associated with an
      increased risk of miscarriage. Further work in larger populations is warranted.

PMID- 24666756
TI  - Delayed diagnosis of human immunodeficiency virus infection in a patient with non
      specific neurological symptoms and pancytopenia: a case report.
AB  - INTRODUCTION: Both non-specific presentation and asymptomatic course of human
      immunodeficiency virus infection lead to undiagnosed long-term persistence of the
      virus in a patient's organism. CASE PRESENTATION: Here, we present a case of a 31
      year-old Caucasian man with non-specific neurological symptoms and pancytopenia,
      who was referred to an internal medicine ward for further diagnosis. Upon
      admission to our hospital, he denied any past risky behaviors and refused to have
      his blood collected for human immunodeficiency virus testing. Later, he
      eventually provided consent to conduct the human immunodeficiency virus test
      which turned out to have a positive result. The overall clinical pattern
      indicated an advanced-stage of acquired immunodeficiency syndrome, which
      contrasted with the history he had provided. CONCLUSIONS: This case report
      indicates the need to consider human immunodeficiency virus/acquired
      immunodeficiency syndrome diagnosis in patients with non-specific neurological
      and hematological disorders. Our report also demonstrates difficulties that can
      be experienced by the physician while trying to obtain both a clear history and
      consent to perform human immunodeficiency virus testing.

PMID- 24666759
TI  - Changes in liver stiffness using acoustic radiation force impulse imaging in
      patients with obstructive cholestasis and cholangitis.
AB  - BACKGROUND: Acoustic radiation force impulse imaging is used to assess stages of
      liver fibrosis. The aim of our study was to evaluate liver stiffness changes in
      patients with biliary obstruction with or without sclerosing cholangitis after
      biliary drainage. METHODS: A total of 71 patients were enrolled in this
      prospective study (cohort N=51, control group N=20); 51 patients with obstructive
      cholestasis, indicated for endoscopic retrograde cholangiography, received
      stiffness measurement by acoustic radiation force impulse imaging before and 1-2
      days after endoscopic retrograde cholangiography. Seventeen patients with
      obstructive cholestasis had primary or secondary sclerosing cholangitis. Forty
      one patients had a follow-up acoustic radiation force impulse imaging measurement
      after 3.0 +/- 9.31 weeks. RESULTS: In all patients with obstructive cholestasis,
      stiffness decreased significantly after biliary drainage (p<0.001). The main
      decrease was observed within 2 days after endoscopic retrograde cholangiography
      (1.92-1.57 m/s, p<0.001) and correlated with the decrease of bilirubin and
      alkaline phosphatase (p=0.04 and p=0.002, respectively). In patients with
      sclerosing cholangitis, the initial decrease of stiffness after biliary drainage
      was weaker than in those without (2.1-1.85 m/s vs. 1.81-1.43 m/s, p=0.016).
      CONCLUSION: Acoustic radiation force impulse imaging elastography shows that
      liver stiffness is increased by biliary obstruction, and decreases after
      endoscopic retrograde cholangiography irrespective of the aetiology. In patients
      with sclerosing cholangitis the reduction in stiffness after biliary drainage is
      impaired.

PMID- 24666760
TI  - Objectively measured physical activity levels of young children with congenital
      heart disease.
AB  - Physical activity tends to be lower in school-age children with congenital heart
      disease than in healthy controls. To the best of our knowledge, objectively
      measured physical activity levels of preschool-age children with congenital heart
      disease have not been studied. METHODS: A total of 10 children with either
      coarctation of the aorta (n=6; age 3.8+/-0.9) or tetralogy of Fallot (n=4, age
      4.3+/-0.9) were recruited from the cardiology unit of McMaster Children's
      Hospital. Height (103.7+/-8.2 cm) and weight (17.3+/-2.7 kg) measurements were
      recorded, and physical activity was determined using accelerometry over 7
      consecutive days. Patients were compared with age-, sex-, and season of data
      acquisition-matched controls. Parents completed a questionnaire regarding the
      child's physical activity and sedentary behaviours. RESULTS: Patients spent on
      average 219.4+/-39.9 minutes engaged in total physical activity per day at the
      following intensities: light, 147.5+/-22.3; moderate, 44.0+/-11.8; moderate-to
      vigorous, 71.9+/-22.6; and vigorous, 27.9+/-11.7. No significant differences were
      observed between patients and controls for total physical activity (p=0.80) or
      any of the intensities (p=0.71, 0.46, 0.43, and 0.45, respectively). Only 40% of
      patients and controls met the new Canadian Physical Activity Guidelines for the
      Early Years of at least 180 minutes of physical activity at any intensity every
      day. Of the patients' parents, 90% believed that their child was as active, if
      not more active, than his/her siblings, and 80% of parents reported their child
      spending 1-3 hours in screen time activities daily. CONCLUSION: Children aged 3-5
      years old with congenital heart disease have comparable physical activity levels
      to age-, sex-, and season-matched controls, and many do not meet Canadian
      Physical Activity Guidelines.

PMID- 24666761
TI  - The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to
      human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) causes a highly prevalent and lifelong infection,
      with a multifaceted impact in human health. NK cells play an important role in
      the immune response to HCMV and the virus has reciprocally developed a variety of
      immune evasion strategies. We originally reported that HCMV infection promotes,
      to a variable degree in healthy individuals, a redistribution of the NK-cell
      receptor (NKR) repertoire which persists under steady-state conditions. Its
      hallmark is an expansion of a mature NK-cell subset displaying high surface
      levels of the CD94/NKG2C activating receptor, with additional distinctive
      phenotypic and functional features. Such adaptation of host NK cells to HCMV
      infection, confirmed in different clinical settings, is particularly magnified in
      immunocompromised patients and influenced by NKG2C gene copy number. The
      mechanism(s) underlying the differentiation and proliferation of NKG2C+ NK cells,
      the basis for the individual differences in the magnitude of their expansion, and
      their precise role in anti-viral defence remain open issues. Moreover, the
      possibility that the impact of HCMV infection on the NK-cell compartment may
      exert a broader influence on immunity deserves further attention. 

PMID- 24666763
TI  - Outcomes of surgical versus endovascular repair of unruptured brain aneurysms in
      individuals aged >= 75 years.
AB  - AIM: Therapeutic intervention to repair unruptured aneurysms (UA) has not been
      strongly recommended for the elderly, because of their limited life expectancy
      and low annual bleeding rate. However, physically and mentally healthy older
      adults with seemingly high risk of aneurysmal bleeding might benefit from having
      their UA repaired. METHODS: A single-center retrospective study was carried out.
      Among 1078 patients admitted for treatment of UA between 2007 and 2011, the
      number of patients aged >= 75 years who underwent surgical and endovascular
      repair of UA was 30 and 31, respectively. The operative and mid-term outcomes
      were compared between the two groups. For evaluation of the operative outcomes,
      frequency and types of adverse events that occurred within 30 days of
      intervention (operative morbidity) were described. For assessment of the mid-term
      outcomes, activities of daily living (ADL) at 24 months after intervention were
      evaluated with the modified Rankin Scale (mRS). RESULTS: The operative morbidity
      rate was 6.7% in the open surgery group and 6.5% in the endovascular surgery
      group, and they did not differ significantly. The frequency of patients with mRS
      0-2 at 24 months after intervention was 85.7% in the open surgery group and 82.8%
      in the endovascular surgery group, and they did not differ significantly. The
      adverse event rate of patients with middle cerebral artery aneurysms treated
      endovascularly was high (80%). CONCLUSIONS: The outcomes of individuals aged >=
      75 years who underwent repair of UA were generally favorable in either treatment
      group, with more than 80% living an independent life at 24 months after
      intervention.

PMID- 24666762
TI  - Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo
      AML cohort.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of
      hemopoietic progenitor cells diagnosed in individuals of any age, but with a
      median age of 67 years at presentation in adults. Assessment of the mutation
      status of nucleophosmin protein-1 (NPM1) and FMS-like tyrosine kinase 3 internal
      tandem duplication (FLT3-ITD) is essential for the prognosis, and treatment of
      AML. METHODS: A total of 160 de novo AML cases, both cytogenetically normal and
      abnormal, were analyzed for the presence of NPM1 and FLT3-ITD mutations, and the
      results assessed in conjunction with epidemiological, clinical, and laboratory
      findings. RESULTS: Nucleophosmin protein-1 mutations were found in 7.5%, while
      FLT3-ITD was present in 12% of these cases. Both of these were lower than
      expected. The median age at diagnosis of AML was 41 years, and for the FLT3-ITD
      only cases, median age was 33 years; these ages were younger than expected.
      CONCLUSION: The lower reported frequencies and younger median age at diagnosis of
      AML and these specific mutations may be contributed to by a number of factors
      including effects of race on age of presentation, inclusion of patients diagnosed
      with de novo AML only, and a generally younger median age of the South African
      population.

PMID- 24666764
TI  - Impact of an educational intervention on hand hygiene compliance and infection
      rate in a developing country neonatal intensive care unit.
AB  - Nosocomial infections are a significant problem in neonatal intensive care units
      (NICUs) and hand hygiene (HH) has been stated as an effective mean to prevent
      spread of infections. The aim of study was to assess the baseline compliance HH
      practices and to evaluate the impact of hand washing educational programme on
      infection rate in a NICU. Continuous surveillance of nosocomial infections was
      done. A total of 15,797 and 12 ,29 opportunities for HH were observed in pre
      intervention and postintervention phases, respectively. Compliance of health-care
      workers for all HH opportunities combined was 46% before intervention and
      improved significantly to 69% in postintervention (RR 1.49, CI 1.46-1.52, P <
      0.0001). Compliance for nurses and doctors was similar. Nosocomial sepsis rate
      showed a significant decline from 96 per 1000 patient-days in pre-intervention to
      47 per 1000 patient-days in postintervention phase (RR 0.44, CI 0.33-0.58, P <
      0.0001). We conclude that effective HH practices can serve as an economical and
      effective nosocomial infection control approach especially important in
      developing nations.

PMID- 24666765
TI  - Effect of once-daily tadalafil on confidence and perceived difficulty in
      performing sexual intercourse in men who were incomplete responders to as-needed
      PDE5 inhibitor treatment.
AB  - INTRODUCTION: For men with erectile dysfunction (ED), the expectation of
      difficulty and level of confidence in achieving and maintaining an erection have
      an impact on sexual performance. OBJECTIVE AND METHODS: This 12-week, double
      blind study investigated once-daily tadalafil (2.5 mg titrated to 5 mg or 5 mg)
      (n = 176) or placebo (n = 79) on confidence and perceived difficulty in
      performing sexual intercourse in men with ED who were incomplete responders to as
      needed phosphodiesterase-5 inhibitor therapy. The Confidence in Performing Sexual
      Intercourse Questionnaire (CPSIQ) and Difficulty in Performing Sexual Intercourse
      Questionnaire (DPSIQ) were administered at baseline and 12 weeks. RESULTS: The
      mean change in CPSIQ for the tadalafil group was 1.8, which represents a shift
      from 'very low' to 'moderate' sexual confidence vs. a mean change of 0.5 in the
      placebo group (p < 0.0001). The mean change in DPSIQ for tadalafil was 1.6, which
      represents a shift from 'very difficult' to 'moderately' or 'slightly difficult'
      sexual performance vs. a mean change of 0.4 in the placebo group (p < 0.0001).
      Among men receiving tadalafil with an International Index of Erectile Function
      Erectile Function (IIEF-EF) end-point score of >= 26 or who achieved a minimal
      clinically important difference in IIEF-EF score at end-point, the mean changes
      in CPSIQ were 3.0 and 2.4, respectively (both p < 0.0001). CONCLUSION: Once-daily
      tadalafil vs. placebo improves confidence and decreases difficulty in performing
      sexual intercourse for men with ED who were incomplete responders to as-needed
      PDE5 inhibitor therapy.

PMID- 24666766
TI  - Mammographic images segmentation based on chaotic map clustering algorithm.
AB  - BACKGROUND: This work investigates the applicability of a novel clustering
      approach to the segmentation of mammographic digital images. The chaotic map
      clustering algorithm is used to group together similar subsets of image pixels
      resulting in a medically meaningful partition of the mammography. METHODS: The
      image is divided into pixels subsets characterized by a set of conveniently
      chosen features and each of the corresponding points in the feature space is
      associated to a map. A mutual coupling strength between the maps depending on the
      associated distance between feature space points is subsequently introduced. On
      the system of maps, the simulated evolution through chaotic dynamics leads to its
      natural partitioning, which corresponds to a particular segmentation scheme of
      the initial mammographic image. RESULTS: The system provides a high recognition
      rate for small mass lesions (about 94% correctly segmented inside the breast) and
      the reproduction of the shape of regions with denser micro-calcifications in
      about 2/3 of the cases, while being less effective on identification of larger
      mass lesions. CONCLUSIONS: We can summarize our analysis by asserting that due to
      the particularities of the mammographic images, the chaotic map clustering
      algorithm should not be used as the sole method of segmentation. It is rather the
      joint use of this method along with other segmentation techniques that could be
      successfully used for increasing the segmentation performance and for providing
      extra information for the subsequent analysis stages such as the classification
      of the segmented ROI.

PMID- 24666767
TI  - The effect of fentanyl and clonidine on early postoperative negative behavior in
      children: a double-blind placebo controlled trial.
AB  - BACKGROUND: Early negative postoperative behavior (e-PONB) is common in children
      and manifests itself as emergence agitation (EA), emergence delirium (ED), and
      pain. The objective of this prospective double blind, randomized, placebo
      controlled trial was to determine whether IV clonidine or IV fentanyl prior to
      surgery modifies e-PONB in children. METHODS: Ninety children scheduled for
      subumbilical surgery under sevoflurane anesthesia supplemented with regional
      anesthesia were randomized to either receive IV clonidine 2 mcg.kg(-1) , IV
      fentanyl 2 mcg.kg(-1) or placebo (IV saline) before surgery. Primary outcome
      measures were the incidence of EA, ED and pain during the first hour after
      awakening. Secondary outcome measures were side effects such as nausea and
      vomiting and delayed discharge from PACU. RESULTS: Eighty-seven children (n = 29
      per group) completed the study. EA was present in 10 children (six clonidine,
      none fentanyl, and four placebo, P = 0.04) whereas ED was observed in 20 children
      (nine clonidine, three fentanyl, and eight placebo P = 0.13). Sixteen children
      who received placebo had a CHIPPS score of >=4 compared with nine children in
      fentanyl group and 18 children receiving clonidine (P = 0.04). Ten children
      receiving fentanyl vomited during the first postoperative day, compared with six
      children in placebo group and none in clonidine group (P = 0.003). Discharge from
      PACU was not affected. CONCLUSIONS: IV fentanyl before surgery but not IV
      clonidine modifies e-PONB in children undergoing lower abdominal surgery under
      general anesthesia supplemented with regional anesthesia. The use of fentanyl in
      this population was also associated with reduced pain scores after awakening but
      with significantly greater incidence of PONV.

PMID- 24666769
TI  - Comparison of problems and unmet needs of patients with advanced cancer in a
      European country and an Asian country.
AB  - BACKGROUND: Patients with advanced cancer experience problems and unmet needs.
      However, we assume that patients with advanced cancer will have more problems and
      unmet needs in a country with a lower economic status than in an economically
      stronger country. We studied whether patients with advanced cancer in Indonesia
      have more problems and unmet needs than a similar group of patients in the
      Netherlands. METHODS: We performed a cross-sectional survey. We compared the data
      for 180 Indonesian and 94 Dutch patients relating to 24 items of the Problems and
      Needs in Palliative Care-short version questionnaire. We performed descriptive
      and chi(2) analysis with Bonferroni correction. RESULTS: The prevalence of most
      physical problems, including pain, was similar in the 2 groups. In Indonesia,
      financial problems were the most common: 70 to 80% vs. 30 to 42% in the
      Netherlands. In Indonesia, 25 to 50% of the patients reported psychological and
      autonomy problems versus 55 to 86% in the Netherlands. The Indonesian group had
      many more unmet needs for each problem (> 54%) than the Dutch group (< 35%).
      CONCLUSION: Apparently, economic and cultural differences hardly influence
      physical problems. Nonetheless, fewer Indonesian patients reported psychological
      and autonomy problems than Dutch patients. This difference contradicts our
      hypothesis. However, we found more unmet needs for professional attention in
      Indonesia than in the Netherlands, which is compatible with our hypothesis. These
      simple comparative data provide interesting insights into problems and unmet
      needs and give rise to our new hypothesis about cultural influences. This
      hypothesis should be studied in more depth.

PMID- 24666768
TI  - Mast cells: versatile gatekeepers of pain.
AB  - Mast cells are important first responders in protective pain responses that
      provoke withdrawal from intense, noxious environmental stimuli, in part because
      of their sentinel location in tissue-environment interfaces. In chronic pain
      disorders, the proximity of mast cells to nerves potentiates critical molecular
      cross-talk between these two cell types that results in their synergistic
      contribution to the initiation and propagation of long-term changes in pain
      responses via intricate signal networks of neurotransmitters, cytokines and
      adhesion molecules. Both in rodent models of inflammatory pain and chronic pain
      disorders, as well as in increasing evidence from the clinic, it is abundantly
      clear that understanding the mast cell-mediated mechanisms underlying protective
      and maladaptive pain cascades will lead to improved understanding of mast cell
      biology as well as the development of novel, targeted therapies for the treatment
      and management of debilitating pain conditions. 

PMID- 24666771
TI  - Determination of hematological and immunological parameters among HIV positive
      patients taking highly active antiretroviral treatment and treatment naive in the
      antiretroviral therapy clinic of Gondar University Hospital, Gondar, Northwest
      Ethiopia: a comparative cross-sectional study.
AB  - BACKGROUND: Anemia, leucopenia and thrombocytopenia are the commonest
      hematological abnormalities resulting from human immunodeficiency virus
      infection. The use of antiretroviral drugs could positively or negatively affect
      these disorders. Thus a specific diagnosis and a determination of hematological
      and immunological parameters are required for initiating and monitoring early
      treatment to avert disease progression. Therefore, this study aimed to compare
      hematological and immunological parameters in HIV positive patients taking
      antiretroviral therapy and those treatment naive patients in Gondar University
      Hospital. METHODS: A comparative cross-sectional study was conducted on a total
      of 290 HIV patients from February to May 2012 in Gondar University Hospital.
      Study subjects were divided in to two groups: 145 HIV positive treatment naive
      and 145 on HAART. Data of socio demographic characteristics and clinical
      conditions of the study subjects was collected using structured pretested
      questionnaire at their follow up date. Hematological and immunological parameters
      were collected and processed by cell Dyne 1800 and BD FACS count respectively.
      The variables compared here were Hematological parameters (Total and differential
      WBC, RBC, Hgb, HCT, MCV, MCH, MCHC, RDW, PLT, and MPV) and CD4 count. In order to
      compare means independent sample T-test was conducted using SPSS version 20
      statistical software. P- Value < 0.05 was considered as significant. RESULT:
      Prevalence of anemia, leucopenia, thrombocytopenia, neutropenia and lymphopenia
      were 11.7%, 35.9%, 4.1%, 28.3% and 2.1% in patients on HAART and 29.7%, 16.6%,
      9%, 14.5% and 2.1% in HAART naive patients respectively. There was a significant
      difference in total WBC, RBC, Hgb, MCV, MCH, MCHC, MPV and CD4 counts between
      patients on HAART and HAART naive patients. CONCLUSION: Prevalence of anemia was
      high in HAART naive patients while leucopenia and neutropenia prevalence was
      higher in patients on HAART and their prevalence increased as the CD4 count
      decreased. HIV Patients should be investigated for hematological and
      immunological changes following with appropriate therapeutic interventions.

PMID- 24666770
TI  - Associations between the school food environment, student consumption and body
      mass index of Canadian adolescents.
AB  - BACKGROUND: Increasing attention has been paid to the school food environment as
      a strategy to reduce childhood obesity. The purpose of this study was to examine
      associations between the school food environment, students' dietary intake, and
      obesity in British Columbia (BC), Canada. METHODS: In 2007/08, principal
      responses about the school environment (N=174) were linked to grades 7-12
      students (N=11,385) from corresponding schools, who participated in the BC
      Adolescent Health Survey. Hierarchical mixed-effect regression analyses examined
      the association between the school food environment and student's intake of sugar
      sweetened beverages (SSBs), food consumption, and body mass index. Analyses
      controlled for school setting, neighborhood education level and student's age and
      sex. RESULTS: School availability of SSBs was positively associated with moderate
      (Odds Ratio (OR)=1.15, 95% Confidence Interval (CI)=1.02-1.30) and high (OR=1.43,
      95% CI=1.13-1.80) SSB intake as were less healthful school nutrition guidelines
      for moderate SSB consumers only (OR=0.65, 95% CI=0.48-0.88). Availability of SSBs
      at school and its consumption were positively associated with student obesity
      (OR=1.50, 95% CI=1.12-2.01 and OR=1.66, 95% CI=1.19-2.34, respectively) but not
      with overweight. In contrast, consumption of less healthful food was positively
      associated with overweight (OR=1.03, 95% CI=1.01-1.06). CONCLUSIONS: The results
      of this study provide further evidence to support the important role of schools
      in shaping adolescents' dietary habits. Availability and consumption of SSBs, but
      not less healthful foods, at school were associated with higher adolescent
      obesity highlighting that other environments also contribute to adolescent
      obesity.

PMID- 24666772
TI  - Congestive heart failure self-management among US veterans: The role of personal
      and professional advocates.
AB  - OBJECTIVE: Understand patients' experiences with primary care services for
      congestive heart failure (CHF) and explore the relationship between health
      services and self-management. METHODS: We conducted semi-structured interviews
      with thirty-nine patients with CHF receiving care at one Veterans Affairs Medical
      Center (VA). We analyzed data using thematic content analysis. RESULTS:
      Participants acknowledged the importance of ongoing engagement in the plan of
      care for CHF. They attributed success in this effort to be greatly influenced by
      personal advocates. The advocates included both members of the healthcare team
      with whom they had a continuity relationship and friends or family members who
      assisted on a daily basis. Participants also identified psychological symptoms as
      a major barrier to carrying out self-care. CONCLUSION: Patients identify
      relationships with health care workers, help from family and friends, and mental
      health problems as major influences on the ability to manage their CHF. PRACTICE
      IMPLICATIONS: Efforts to optimize CHF self-management should attend to health
      system and psychosocial barriers to care.

PMID- 24666773
TI  - Mandatory communication training of all employees with patient contact.
AB  - In 2010 a communication program that included mandatory communication skills
      training for all employees with patient contact was developed and launched at a
      large regional hospital in Denmark. OBJECTIVE: We describe the communication
      program, the implementation process, and the initial assessment of the process to
      date. METHOD: The cornerstone of the program is a communication course based on
      the Calgary Cambridge Guide and on the experiences of several efficacy and
      effectiveness studies conducted at the same hospital. The specific elements of
      the program are described in steps and a preliminary assessment based on feedback
      from the departments will be presented. RESULTS: The elements of the
      communication program are as follows: (1) education of trainers; (2) courses for
      health professionals employed in clinical departments; (3) education of new
      staff; (4) courses for health professionals in service departments; and (5)
      maintenance of communication skills. Thus far, 70 of 86 staff have become
      certified trainers and 17 of 18 departments have been included in the program.
      CONCLUSION AND PRACTICE IMPLICATIONS: Even though the communication program is
      resource-intensive and competes with several other development projects in the
      clinical departments, the experiences of the staff and the managers are positive
      and the program continues as planned.

PMID- 24666774
TI  - Thinking outside the black box: the importance of context in understanding the
      impact of a preoperative education nursing intervention among Chinese cardiac
      patients.
AB  - OBJECTIVE: In a randomized controlled trial of a preoperative education
      intervention conducted for Chinese cardiac patients, we observed a greater effect
      on symptoms of anxiety and depression than that reported with regard to similar
      interventions in western care settings. The objective of this qualitative study
      was to help explain the findings of the trial by exploring Chinese patients'
      experience of seeking and receiving information before cardiac surgery. METHODS:
      Semi-structured interviews were conducted with a purposive sample of 20 trial
      participants before discharge (ten from the preoperative education group; ten
      from the usual care control group). Data were analyzed using a thematic analysis
      approach. RESULTS: A total of five themes were generated: the role of reputation
      and hierarchy; gaining strength from knowledge; information as a low priority;
      being kept in the dark; and learning through peer support. CONCLUSION: In health
      care systems where service users are given relatively little information,
      interventions designed to inform patients about their treatment are likely to
      have a much greater impact on their psychological health. PRACTICE IMPLICATIONS:
      Providers of services for patients undergoing cardiac surgery in China should be
      encouraged to incorporate information giving into routine practice, tailored
      according to individual need.

PMID- 24666775
TI  - Abstracts of the Forty Second Annual Meeting International Neuropsychological
      Society, February 12-15, 2014, Seattle, Washington, USA.

PMID- 24666776
TI  - From SNP co-association to RNA co-expression: novel insights into gene networks
      for intramuscular fatty acid composition in porcine.
AB  - BACKGROUND: Fatty acids (FA) play a critical role in energy homeostasis and
      metabolic diseases; in the context of livestock species, their profile also
      impacts on meat quality for healthy human consumption. Molecular pathways
      controlling lipid metabolism are highly interconnected and are not fully
      understood. Elucidating these molecular processes will aid technological
      development towards improvement of pork meat quality and increased knowledge of
      FA metabolism, underpinning metabolic diseases in humans. RESULTS: The results
      from genome-wide association studies (GWAS) across 15 phenotypes were subjected
      to an Association Weight Matrix (AWM) approach to predict a network of 1,096
      genes related to intramuscular FA composition in pigs. To identify the key
      regulators of FA metabolism, we focused on the minimal set of transcription
      factors (TF) that the explored the majority of the network topology. Pathway and
      network analyses pointed towards a trio of TF as key regulators of FA metabolism:
      NCOA2, FHL2 and EP300. Promoter sequence analyses confirmed that these TF have
      binding sites for some well-know regulators of lipid and carbohydrate metabolism.
      For the first time in a non-model species, some of the co-associations observed
      at the genetic level were validated through co-expression at the transcriptomic
      level based on real-time PCR of 40 genes in adipose tissue, and a further 55
      genes in liver. In particular, liver expression of NCOA2 and EP300 differed
      between pig breeds (Iberian and Landrace) extreme in terms of fat deposition.
      Highly clustered co-expression networks in both liver and adipose tissues were
      observed. EP300 and NCOA2 showed centrality parameters above average in the both
      networks. Over all genes, co-expression analyses confirmed 28.9% of the AWM
      predicted gene-gene interactions in liver and 33.0% in adipose tissue. The
      magnitude of this validation varied across genes, with up to 60.8% of the
      connections of NCOA2 in adipose tissue being validated via co-expression.
      CONCLUSIONS: Our results recapitulate the known transcriptional regulation of FA
      metabolism, predict gene interactions that can be experimentally validated, and
      suggest that genetic variants mapped to EP300, FHL2, and NCOA2 modulate lipid
      metabolism and control energy homeostasis in pigs.

PMID- 24666778
TI  - Estimating the impact of somatic cell count on the value of milk utilising
      parameters obtained from the published literature.
AB  - The impact of mastitis on milk value per litre independent of the effect of
      mastitis on milk volume, was quantified for Ireland using a meta-analysis and a
      processing sector model. Changes in raw milk composition, cheese processing and
      composition associated with increased bulk milk somatic cell count (BMSCC) were
      incorporated into the model. Processing costs and market values were
      representative of current industry values. It was assumed that as BMSCC increased
      (i) milk fat and milk protein increased and milk lactose decreased, (ii) fat and
      protein recoveries decreased, (iii) cheese protein decreased and cheese moisture
      increased. Five BMSCC categories were examined from ?100 000 to >400 000
      cells/ml. The analysis showed that as BMSCC increased the production quantities
      reduced. An increase in BMSCC from 100 000 to >400 000 cells/ml saw a reduction
      in net revenue of 3.2% per annum (?51.3 million) which corresponded to a
      reduction in the value of raw milk of ?0.0096 cents/l. 

PMID- 24666777
TI  - Honey - a potential agent against Porphyromonas gingivalis: an in vitro study.
AB  - BACKGROUND: Honey has been discussed as a therapeutic option in wound healing
      since ancient time. It might be also an alternative to the commonly used
      antimicrobials in periodontitis treatment. The in-vitro study was aimed to
      determine the antimicrobial efficacy against Porphyromonas gingivalis as a major
      periodontopathogen. METHODS: One Manuka and one domestic beekeeper honey have
      been selected for the study. As a screening, MICs of the honeys against 20 P.
      gingivalis strains were determined. Contents of methylglyoxal and hydrogen
      peroxide as the potential antimicrobial compounds were determined. These
      components (up to 100 mg/l), propolis (up to 200 mg/l) as well as the two honeys
      (up to 10% w/v) were tested against four P. gingivalis strains in planktonic
      growth and in a single-species biofilm. RESULTS: 2% of Manuka honey inhibited the
      growth of 50% of the planktonic P. gingivalis, the respective MIC50 of the German
      beekeeper honey was 5%. Manuka honey contained 1.87 mg/kg hydrogen peroxide and
      the domestic honey 3.74 mg/kg. The amount of methylglyoxal was found to be 2
      mg/kg in the domestic honey and 982 mg/kg in the Manuka honey. MICs for hydrogen
      peroxide were 10 mg/l - 100 mg/l, for methylglyoxal 5 - 20 mg/l, and for propolis
      20 mg/l - 200 mg/l. 10% of both types of honey inhibited the formation of P.
      gingivalis biofilms and reduced the numbers of viable bacteria within 42 h-old
      biofilms. Neither a total prevention of biofilm formation nor a complete
      eradication of a 42 h-old biofilm by any of the tested compounds and the honeys
      were found. CONCLUSIONS: Honey acts antibacterial against P. gingivalis. The
      observed pronounced effects of Manuka honey against planktonic bacteria but not
      within biofilm can be attributed to methylglyoxal as the characteristic
      antimicrobial component.

PMID- 24666779
TI  - Adaptation to short photoperiods augments circadian food anticipatory activity in
      Siberian hamsters.
AB  - This article is part of a Special Issue "Energy Balance". Both the light-dark
      cycle and the timing of food intake can entrain circadian rhythms. Entrainment to
      food is mediated by a food entrainable circadian oscillator (FEO) that is
      formally and mechanistically separable from the hypothalamic light-entrainable
      oscillator. This experiment examined whether seasonal changes in day length
      affect the function of the FEO in male Siberian hamsters (Phodopus sungorus).
      Hamsters housed in long (LD; 15 h light/day) or short (SD; 9h light/day)
      photoperiods were subjected to a timed-feeding schedule for 10 days, during which
      food was available only during a 5h interval of the light phase. Running wheel
      activity occurring within a 3h window immediately prior to actual or anticipated
      food delivery was operationally-defined as food anticipatory activity (FAA).
      After the timed-feeding interval, hamsters were fed ad libitum, and FAA was
      assessed 2 and 7 days later via probe trials of total food deprivation. During
      timed-feeding, all hamsters exhibited increases FAA, but FAA emerged more rapidly
      in SD; in probe trials, FAA was greater in magnitude and persistence in SD.
      Gonadectomy in LD did not induce the SD-like FAA phenotype, indicating that
      withdrawal of gonadal hormones is not sufficient to mediate the effects of
      photoperiod on FAA. Entrainment of the circadian system to light markedly affects
      the functional output of the FEO via gonadal hormone-independent mechanisms.
      Rapid emergence and persistent expression of FAA in SD may reflect a seasonal
      adaptation that directs behavior toward sources of nutrition with high temporal
      precision at times of year when food is scarce.

PMID- 24666780
TI  - Oncology scan--defining dose, fractionation, and target volume in small cell lung
      cancer.

PMID- 24666781
TI  - Retracted: Executive functions in chronic hepatitis C virus infected elderly
      patients.

PMID- 24666782
TI  - Acute cocaine-related health problems in patients presenting to an urban
      emergency department in Switzerland: a case series.
AB  - BACKGROUND: Emergency departments may be a useful information source to describe
      the demographics and clinical characteristics of patients with acute cocaine
      related medical problems. We therefore conducted a retrospective analysis of 165
      acute, laboratory-confirmed cocaine intoxications admitted to an urban emergency
      department in Switzerland between January 2007 and March 2011. RESULTS: A total
      of 165 patients with a mean age of 32 years were included. Most patients were
      male (73%) and unemployed (65%). Only a minority (16%) had abused cocaine alone
      while 84% of the patients had used at least one additional substance, most
      commonly ethanol (41%), opioids (38%), or cannabis (36%) as confirmed by their
      detection in blood samples. The most frequently reported symptoms were chest pain
      (21%), palpitations (19%), anxiety (36%) and restlessness (36%). Psychiatric
      symptoms were present in 64%. Hypertension and tachycardia were observed in 53%
      and 44% of the patients, respectively. Severe poisonings only occurred in
      patients with multiple substance intoxication (15%). Severe intoxications were
      non-significantly more frequent with injected drug use compared to nasal, oral,
      or inhalational drug use. Severe complications included acute myocardial
      infarction (2 cases), stroke (one case), and seizures (3 cases). Most patients
      (75%) were discharged home within 24 h after admission. A psychiatric evaluation
      in the ED was performed in 24% of the patients and 19% were referred to a
      psychiatric clinic. CONCLUSIONS: Patients with acute cocaine intoxication often
      used cocaine together with ethanol and opioids and presented with sympathomimetic
      toxicity and/or psychiatric disorders. Severe acute toxicity was more frequent
      with multiple substance use. Toxicity was typically short-lasting but psychiatric
      evaluation and referral was often needed.

PMID- 24666783
TI  - Percutaneous management of coronary sinus atrial septal defect: two cases
      representing the spectrum for device closure and a review of the literature.
AB  - Coronary sinus atrial septal defects are the rarest defects of the atrial septum
      comprising <1% of the five different types of atrial septal defects. Despite the
      widespread adoption of percutaneous device closure of secundum atrial septal
      defects, the published experience with percutaneous device closure of coronary
      sinus atrial septal defects is limited to only a few isolated case reports
      because of uncertainty regarding safety and efficacy. Open-heart surgical repair
      remains the treatment of choice for coronary sinus atrial septal defects,
      although this may not be the only treatment option in selected cases. Herein we
      describe our own experience with two patients with different clinical
      presentations and our method of successful percutaneous coronary sinus atrial
      septal defect closure in each. We then present a review of the anatomic spectrum
      of coronary sinus atrial septal defects along with a review of contemporary
      surgical and percutaneous device treatment. 

PMID- 24666784
TI  - Recovery of linear and nonlinear heart rate dynamics after coronary artery bypass
      grafting surgery.
AB  - BACKGROUND: Conventional coronary artery bypass grafting (C-CABG) and off-pump
      CABG (OPCAB) surgery may produce different patients' outcomes, including the
      extent of cardiac autonomic (CA) imbalance. The beneficial effects of an exercise
      based inpatient programme on heart rate variability (HRV) for C-CABG patients
      have already been demonstrated by our group. However, there are no studies about
      the impact of a cardiac rehabilitation (CR) on HRV behaviour after OPCAB. The aim
      of this study is to compare the influence of both operative techniques on HRV
      pattern following CR in the postoperative (PO) period. METHODS: Cardiac autonomic
      function was evaluated by HRV indices pre- and post-CR in patients undergoing C
      CABG (n = 15) and OPCAB (n = 13). All patients participated in a short-term
      (approximately 5 days) supervised CR programme of early mobilization, consisting
      of progressive exercises, from active-assistive movements at PO day 1 to climbing
      flights of stairs at PO day 5. RESULTS: Both groups demonstrated a reduction in
      HRV following surgery. The CR programme promoted improvements in HRV indices at
      discharge for both groups. The OPCAB group presented with higher HRV values at
      discharge, compared to the C-CABG group, indicating a better recovery of CA
      function. CONCLUSION: Our data suggest that patients submitted to OPCAB and an
      inpatient CR programme present with greater improvement in CA function compared
      to C-CABG.

PMID- 24666785
TI  - Internationally recruited neonatal nurses' experiences in the National Health
      Service in London.
AB  - The aim of this study was to explore internationally recruited neonatal nurses'
      (IRNNs) perceptions of their experiences of working in the National Health
      Service (NHS) in London. This was an exploratory study. A purposive sample of 13
      nurses (all females) from two teaching hospitals in London participated in this
      study. Semi-structured face-to-face interviews were used to capture IRNNs views
      of working in the NHS in London. Five themes emerged, namely: motivation to
      migrate, lack of preparation for neonatal nurses, environmental conditions
      impacting on care delivery, neonatal nurses deskilling, and role restrictions as
      well as professional development. The findings of this study provide first-hand
      insights from the subjective perspectives of IRNN experiences. IRNNs experienced
      some challenges to their working lives; however, good preparation is important
      when recruiting them to work in the NHS. 

PMID- 24666786
TI  - [Menetriers disease associated with cytomegalovirus infection].
AB  - Menetrier's disease is a rare entity in children, characterized by a protein
      losing gastroenteropathy with thickening of the gastric mucosa and generalized
      edema. The most common etiology is viral, and cytomegalovirus is the agent most
      frequently implicated. Unlike in the adult, it is a self-limited disorder with a
      good prognosis in children. Four patients (three boys and one girl) diagnosed
      with Menetrier disease in the past five years were reviewed. The mean age at
      presentation was 28.7 months (range: 10-48 months). The most common clinical
      symptoms were fever, vomiting, and edema. Endoscopy showed thickened gastric
      folds and erosions in several stages. All patients had an associated gastric
      cytomegalovirus infection, and a favorable outcome, with resolution of the
      disorder,was observed within a few weeks. 

PMID- 24666787
TI  - [Positive smooth muscle antibody without autoimmune hepatitis].

PMID- 24666788
TI  - [Influence of medical and neuropsychiatric comorbidities on the course of
      childhood epilepsy].
AB  - INTRODUCTION: Comorbidity has a significant influence in the management of
      patients with epilepsy. MATERIAL AND METHODS: A descriptive study of all patients
      with epilepsy, from a suburban area in the Community of Madrid followed up for at
      least 1 year. Children under 2 years, those with symptomatic acute febrile
      seizures were excluded. RESULTS: Out of a total of 46 patients (54% male, age
      median 9.1 years), more than half (52.5%) were on monotherapy, 45.7% were "free
      of seizures", 23.9% had "drug resistant epilepsy", and 30.4% were "undetermined".
      As regards comorbidities, 28.3% had chronic medical conditions, and 41.3%
      associated neuropsychiatric disorders. In32.6%, the seizures were of sudden
      onset, and those with chronic medical and neuropsychiatric comorbidities had a
      risk of 15 and 8.3 times, respectively, than those patients without
      comorbidities. CONCLUSIONS: Comorbidities may have an important role in the
      course of epilepsy.

PMID- 24666789
TI  - Transient abdominal wall deformity in an infant Blaming the caudal?
AB  - Locoregional anesthesia is an important aspect of perioperative analgesia. It
      decreases requirements for anesthetic agents and opioids, decreases the surgical
      stress response, and provides postoperative analgesia. Nonetheless, pediatric
      patients, especially infants, demonstrate specificities towards regional
      anesthesia techniques, as an increased sensitivity to local anesthetics (LA) and
      a higher ease of LA spread especially when using blocks that rely on the volume
      of LA and its spread as those used for abdominal wall analgesia or caudal. Thus,
      we present a case of transient abdominal wall deformity following caudal
      anesthesia in an infant. 

PMID- 24666790
TI  - On vision in birds: coordination of head-bobbing and gait stabilises vertical
      head position in quail.
AB  - INTRODUCTION: Head-bobbing in birds is a conspicuous behaviour related to vision
      comprising a hold phase and a thrust phase. The timing of these phases has been
      shown in many birds, including quail, to be coordinated with footfall during
      locomotion. We were interested in the biomechanics behind this phenomenon. During
      terrestrial locomotion in birds, the trunk is subjected to gait-specific vertical
      oscillations. Without compensation, these vertical oscillations conflict with the
      demands of vision (i.e., a vertically stable head position). We tested the
      hypothesis that the coordination between head-bobbing and trunk movement is a
      means of reconciling the conflicting demands of vision and locomotion which
      should thus vary according to gait. RESULTS: Significant differences in the
      timing of head-bobbing were found between gaits. The thrust phase was initiated
      just prior to the double support phase in walking (vaulting) trials, whereas in
      running (bouncing) trials, thrust started around midstance. Altering the timing
      of head-trunk-coordination in simulations showed that the timing naturally
      favoured by birds minimizes the vertical displacement of the head. When using a
      bouncing gait the timing of head bobbing had a compensatory effect on the
      fluctuation of the potential energy of the bird's centre of mass. CONCLUSION: The
      results are consistent with expectations based on the vertical trunk fluctuations
      observed in biomechanical models of vaulting and bouncing locomotion. The timing
      of the head-bobbing behaviour naturally favoured by quail benefits vision during
      vaulting and bouncing gaits and potentially helps reducing the mechanical cost
      associated with head bobbing when using a bouncing gait.

PMID- 24666791
TI  - Prevalence of lipid abnormalities and attainment of normal lipid levels among
      patients with dyslipidaemia: a pooled analysis of observational studies from five
      Asian countries.
AB  - AIMS: Guidelines emphasise the importance of low-density lipoprotein cholesterol
      (LDL-C) goals for cardiovascular risk reduction. Given the importance of
      association between high-density lipoprotein (HDL-C) and triglycerides (TG)
      normal levels and cardiovascular risk, there is an additional need to further
      evaluate diverse dyslipidaemic populations. METHODS: A retrospective longitudinal
      observational study of patients aged >= 35 years on lipid-modifying therapy (LMT)
      for >= 12 months was conducted from patient records pooled from five Asian
      countries (Malaysia, Korea, Hong Kong, Thailand and Philippines). The prevalence
      of lipid abnormalities and goal attainment was assessed 12 months before and
      after LMT initiation. RESULTS: Among 3256 patients (mean age - 58.6 years, 50.4%
      men), 65.4% were high-risk patients and 88% were on statin therapy. At baseline
      94.7% of all patients had at least one abnormal lipid value elevated, LDL-C
      (86.2%) being the most prevalent. Non-smokers [OR (95% CI): 1.42 (1.08-1.87)],
      non-diabetics [2.35 (1.96-2.82)], non-cardiovascular disease patients [1.77 (1.42
      2.21)] and those from Korea [2.56 (1.83-3.59)] were more likely to attain LDL-C
      goals. On the contrary, women [0.82 (0.68-0.98)], subjects with FRS > 20% [0.56
      (0.41-0.77)] those from Malaysia [0.55 (0.39-0.77)] and the Philippines [0.18
      (0.12-0.28)] were less likely to reach LDL-C goals. Fewer characteristics were
      independently associated with reaching normal levels of HDL-C and TG and
      attaining at least two normal lipid levels. CONCLUSIONS: While current LMT
      reduced the prevalence of dyslipidaemia, a third of patients still failed to
      achieve target/normal levels. We highlight country differences and the importance
      of improving therapy to attain multiple lipid goals/normal levels.

PMID- 24666793
TI  - The IncI1 plasmid carrying the blaCTX-M-1 gene persists in in vitro culture of a
      Escherichia coli strain from broilers.
AB  - BACKGROUND: Commensal bacteria are a reservoir for antimicrobial-resistance
      genes. In the Netherlands, bacteria producing Extended Spectrum Beta-Lactamases
      (ESBL) are found on chicken-meat and in the gut of broilers at a high prevalence
      and the predominant ESBL-gene is the bla(CTX-M-1) located on IncI1 plasmids. We
      aim to determine the fitness costs of this plasmid for the bacterium.We
      investigated the conjugation dynamics of IncI1 plasmids carrying the bla(CTX-M-1)
      gene in a batch culture and its impact on the population dynamics of three E.
      coli populations: donors, recipients and transconjugants. The intrinsic growth
      rate (psi), maximum density (K) and lag-phase (lambda) of the populations were
      estimated as well as the conjugation coefficient. Loss of the plasmid by
      transconjugants was either assumed constant or depended on the effective growth
      rate of the transconjugants.Parameters were estimated from experiments with pure
      culture of donors, recipients and transconjugants and with mixed culture of
      donors and recipients with a duration of 24 or 48 hours. Extrapolation of the
      results was compared to a 3-months experiment in which a mixed culture of
      recipient and transconjugant was regularly diluted in new medium. RESULTS: No
      differences in estimated growth parameters (psi, K or lambda) were found between
      donor, recipient and transconjugant, and plasmid loss was not observed. The
      conjugation coefficient of transconjugants was 104 times larger than that of the
      donor. In the 3-months experiment, the proportion of transconjugants did not
      decrease, indicating no or very small fitness costs. CONCLUSIONS: In vitro the
      IncI1 plasmid carrying the blaCTX-M-1 gene imposes no or negligible fitness costs
      on its E. coli host, and persists without antimicrobial usage.

PMID- 24666794
TI  - Comment on "Re: Is there a need for a clinical decision rule in blunt wrist
      trauma?".

PMID- 24666795
TI  - Survival and hospitalization among patients with acute myeloid leukemia treated
      with azacitidine or decitabine in a large managed care population: a real-world,
      retrospective, claims-based, comparative analysis.
AB  - BACKGROUND: This study examined patient outcomes using real world data for acute
      myeloid leukemia (AML) patients initiating treatment. METHODS: A retrospective,
      administrative claims-based, comparative analysis was developed to study outcomes
      for AML patients initiating treatment with decitabine or azacitidine between
      January 2006 and June 2012. RESULTS: Treatment with azacitidine was associated
      with a longer median overall survival (10.1 versus 6.9 mos., p = 0.007) and a
      lower risk of hospitalization (HR 0.787, p = 0.02) compared to treatment with
      decitabine. CONCLUSIONS: This analysis of the outcomes of real-world treatment of
      AML patients with demethylating agents suggests that azacitidine may result in
      clinically superior outcomes than decitabine.

PMID- 24666796
TI  - Assessment of tissue oxygenation of periodontal inflammation in patients with
      coronary artery diseases using optical spectroscopy.
AB  - BACKGROUND: We have recently developed a non-invasive periodontal diagnostic tool
      that was validated in periodontitis patients without systemic disorders like
      coronary artery disease (CAD). The purpose of present study is to verify whether
      this optical instrument can also be used in periodontitis patients with CAD.
      METHODS: A total of 62 periodontitis patients with CAD were recruited along with
      a control group consisting of 59 age and gender matched periodontitis volunteers
      without systemic disorders. Using a portable optical near-infrared spectrometer,
      optical spectra were obtained, processed and evaluated from the two groups. A
      modified Beer-Lambert unmixing model that incorporates a nonparametric scattering
      loss function was used to determine the relative contribution of deoxygenated
      hemoglobin (Hb) and oxygenated hemoglobin (HbO2) to the overall spectrum. The
      balance between tissue oxygen delivery and utilization in periodontal tissues was
      then assessed. RESULTS: Tissue oxygen saturation was significantly decreased in
      the periodontitis sites (p < 0.01), compared to the healthy sites in those
      individuals with CAD. There was a trend towards increased concentration of Hb and
      decreased concentration of HbO2 from healthy to diseased sites, without
      statistical significance (p > 0.05). No statistical differences were found in
      tissue oxygen saturation between the CAD and control groups either in periodontal
      healthy or inflammatory sites. CONCLUSION: This study supports the hypothesis
      that optical spectroscopy can determine the periodontal inflammation in patients
      with certain systemic disorders like CAD. And the overall periodontal oxygenation
      profiles in CAD patients resemble those in non-CAD individuals either in healthy
      or inflammatory sites.

PMID- 24666798
TI  - Antenatal prediction of neonatal mortality in very premature infants.
AB  - OBJECTIVE: To develop a prognostic model for antenatal prediction of neonatal
      mortality in infants threatening to be born very preterm (<32 weeks). STUDY
      DESIGN: Nationwide cohort study in The Netherlands between 1999 and 2007. We
      studied 8500 singletons born between 25(+0) and 31(+6) weeks of gestation where
      fetus was alive at birth without congenital anomalies. We developed a multiple
      logistic regression model to estimate the risk of neonatal mortality within 28
      days after birth, based on characteristics that are known before birth. We used
      bootstrapping techniques for internal validation. Discrimination (AUC), accuracy
      (Brier score) and calibration (graph, c-statistics) were used to assess the
      model's predictive performance. RESULTS: Neonatal mortality occurred in 766 (90
      per 1000) live births. The final model consisted of seven variables. Predictors
      were low gestational age, no antental corticosteroids, male gender, maternal age
      >=35 years, Caucasian ethnicity, non-cephalic presentation and non-3rd level of
      hospital. The predicted probabilities ranged from 0.003 to 0.697 (IQR 0.02-0.11).
      The model had an AUC of 0.83, the Brier score was 0.065. The calibration graph
      showed good calibration, and the test for the Hosmer Lemeshow c-statistic showed
      no lack of fit (p=0.43). CONCLUSIONS: Neonatal mortality can be predicted for
      very preterm births based on the antenatal factors gestational age, antental
      corticosteroids, fetal gender, maternal age, ethnicity, presentation and level of
      hospital. This model can be helpful in antenatal counseling.

PMID- 24666799
TI  - Gestational age-dependent risk factors for preterm birth: associations with
      maternal education and age early in gestation.
AB  - OBJECTIVES: Preterm birth (PTB) before 37 weeks can occur over a wide range of
      gestational ages, but few studies have assessed if associations between risk
      factors and PTB vary over the duration of gestation. We sought to evaluate if
      associations between two major risk factors (maternal education and age) and PTB
      depend on gestational age at delivery. STUDY DESIGN: We estimated hazard ratios
      of PTB for education and age in a time-to-event analysis using a retrospective
      cohort of 223,756 live singleton births from the province of Quebec, Canada for
      the years 2001-2005. Differences in hazards of maternal education and age with
      PTB were assessed over gestational age in a Cox proportional hazards model using
      linear and nonlinear time interaction terms, adjusting for maternal
      characteristics. RESULTS: Associations of PTB with lower (vs. higher) education
      and older (vs. younger) age strengthened progressively at earlier gestational
      ages, such that the risk of PTB for maternal education and age was not constant
      over the course of gestation. CONCLUSIONS: Associations of PTB with risk factors
      such as maternal low education and older age may be stronger early in gestation.
      Models that capture the time-dependent nature of PTB may be useful when the goal
      is to assess associations at low gestational ages, and to avoid masked or biased
      associations early in gestation.

PMID- 24666800
TI  - Recurrent miscarriage and birth sex ratio.
AB  - OBJECTIVE: To examine the relationship between birth sex ratio and unexplained
      recurrent miscarriage (RM). STUDY DESIGN: Retrospective, observational study
      including a total of 138 women with primary recurrent miscarriage (PRM) and 170
      women with secondary recurrent miscarriage (SRM) in a tertiary referral recurrent
      miscarriage clinic between 1992 and 2010. The sex ratio of the first birth and
      subsequent birth were the main outcome measures. RESULTS: In women with SRM: (i)
      The male:female sex ratio of the first stillbirth was 10:2, significantly
      (OR=4.76) higher than the male:female sex ratio of 1.05 among all births in UK.
      (ii) When the first born was a male, the male:female sex ratio of the subsequent
      birth was 21:35, significantly (OR=0.57) lower than the sex ratio among the
      general population. (iii) A male firstborn did not affect the chance of a
      subsequent live-birth. The findings did not apply to sex ratio in primary RM.
      CONCLUSION: There was a subtle relationship between the sex of the first and
      subsequent births and secondary recurrent miscarriage, but not primary recurrent
      miscarriage.

PMID- 24666801
TI  - Frailty as a predictor of all-cause mortality in older men and women.
AB  - AIMS: To investigate the modifying effect of sex on the association between
      frailty and all-cause mortality, and to determine the effects of changes in
      frailty status on mortality. METHODS: This population-based study comprised 654
      persons aged 76-100 years (mean age 82 +/- 4.6 years). Frailty status was
      assessed at baseline in 2005, and reassessed in 2007 (n=546) using the
      Cardiovascular Health Study criteria. Death dates were received from the official
      register until the end of 2009. The associations between frailty, changes in
      frailty and mortality were investigated using Cox regression models. RESULTS: At
      baseline, 93 (14%) participants were classified as frail, and 311 (48%) as pre
      frail. Over the 4-year follow up, 173 (27%) baseline respondents died. The
      mortality risk for participants who were frail at baseline was 2.7 (95% CI 1.6
      4.5) compared with the robust. In the fully adjusted model, the association was
      significant for women (HR 2.8, 95% CI 1.5-5.3), and of borderline significance
      for men (HR 2.4, 95% CI 1.0-5.9). In men, pre-frailty and frailty were both
      associated with increased mortality risk only in the age-adjusted model (pre
      frailty HR 2.3, 95% CI 1.2-4.5; frailty HR 4.0, 95% CI 1.9-8.9). Decline in
      frailty status during the 2-year follow-up period also markedly increased the
      risk for mortality over the succeeding 2 years. CONCLUSIONS: Frailty is strongly
      associated with higher mortality, especially among women. Among men, the
      association was explained by baseline functional capacity, comorbidity and
      lifestyle factors. Changes in frailty status should also be taken into
      consideration when planning geriatric care, as such changes could indicate a more
      rapid decline in health.

PMID- 24666802
TI  - Prospective, randomised, controlled trial comparing delivery of patient
      information for functional endoscopic sinus surgery via website versus printed
      leaflet.
AB  - OBJECTIVE: To compare the efficacy of two modes of delivery of information for
      patients undergoing functional endoscopic sinus surgery: website and printed
      leaflet. METHODS: A two-centre, prospective, single-blinded, randomised,
      controlled trial was conducted, comparing mode of information delivery. Adult
      patients were randomly allocated to receive pre-operative information regarding
      functional endoscopic sinus surgery, either via a website or a printed leaflet.
      Primary outcomes, measured by questionnaire, were: readability, usability and
      recall of complications. RESULTS: Fifty-eight patients were recruited. Fifty met
      the inclusion criteria, of which 40 were analysed in the study (20 patients per
      group), meeting the power criteria set. There were 18 male and 22 female
      patients, ranging in age from 21 to 76 years (mean, 47 years). Patients found
      both the printed leaflet and the website readable, and were satisfied with the
      usability of both modes. There were similar rates for recall of complications in
      both study arms. CONCLUSION: Patient information on functional endoscopic sinus
      surgery can be provided either as a printed leaflet or a website, with similar
      rates for usability, readability and recall of complications. These findings
      could help tailor the provision of pre-operative information for patients
      undergoing functional endoscopic sinus surgery, based on patient preference.

PMID- 24666803
TI  - Hypocalcaemia following total thyroidectomy: early post-operative parathyroid
      hormone assay as a risk stratification and management tool.
AB  - OBJECTIVE: To develop a practical, efficient and predictive algorithm to manage
      potential or actual post-operative hypocalcaemia after complete thyroidectomy,
      using a single post-operative parathyroid hormone assay. METHODS: This paper
      reports a prospective study of 59 patients who underwent total or completion
      thyroidectomy over a period of 24 months. Parathyroid hormone levels were checked
      post-operatively on the day of surgery, and all patients were evaluated for
      hypocalcaemia both clinically and biochemically with serial corrected calcium
      measurements. RESULTS: No patient with an early post-operative parathyroid
      hormone level of 23 ng/l or more (i.e. approximately twice the lower limit of the
      normal range) developed hypocalcaemia. All the patients who initially had post
      operative hypocalcaemia but had an early parathyroid hormone level of 8 ng/l or
      more (i.e. approximately two-thirds of the lower limit of the normal range) had
      complete resolution of their hypocalcaemia within three months. CONCLUSION: Early
      post-operative parathyroid hormone measurement can reliably predict patients at
      risk of post-thyroidectomy hypocalcaemia, and predict those patients expected to
      recover from temporary hypocalcaemia. A suggested post-operative management
      algorithm is presented.

PMID- 24666805
TI  - Prevalence of overweight and obesity among patients with congenital and acquired
      heart disease in Kocaeli, Turkey.
AB  - BACKGROUND: Childhood obesity has increased in the last half of the century. The
      aim of this study was to evaluate the frequency of obesity in the children with
      congenital or acquired heart disease. METHODS: A total of 1410 children were
      assessed in this study. The study population was composed of 518 children (289
      boys, 229 girls) as control group and 892 children (477 boys, 415 girls) as heart
      disease group. Patients were grouped into four categories: (I) "Clinic control
      subjects"; (II) "mild heart disease" that has not been treated with either
      surgical or catheter intervention; (III) congenital heart disease treated with
      surgical and/or catheter intervention; and (IV) "arrhythmias". A body mass index
      ?85th percentile was defined as overweight, ?95th percentile as obese, and <5th
      percentile was defined as underweight. RESULTS: We did not detect any association
      between heart disease and obesity. There was no difference in the rates of
      overweight, obesity, and underweight between the healthy control subjects and
      patients with heart disease (8.1%, 13.3%, and 5.0%; 9.0%, 10.7%, and 4.7%,
      respectively, p=0.145). All subgroups had a similar prevalence of underweight,
      overweight, and obesity as the healthy control population. Within the heart
      disease population, the overall prevalence rates for overweight, obesity, and
      underweight were similar between the boys and girls. CONCLUSION: Obesity is a
      common problem in children with heart disease, at least in general population. It
      is an important additional risk factor for long-term cardiovascular morbidity and
      mortality in children with heart disease. Precautions to prevent obesity should
      be a part of paediatric cardiologist's examination.

PMID- 24666806
TI  - Juvenile xanthogranuloma: a case report and review of the literature.
AB  - BACKGROUND: Juvenile xanthogranuloma is a rare disorder which may be present at
      birth, or appears in infancy. It can also occur in adults of all ages; appears
      with lesions that may be solitary or multiple nodules several millimeters in
      diameter. The predilection sites are head and neck, but it may occur on the
      extremities and trunk also. There can also be involved internal organs such as
      lung, kidney, gastrointestinal tract, etc. The most frequent extracutaneous
      location is the eye. CASE PRESENTATION: We report a case of juvenile
      xanthogranuloma in a male child with onset in the fourth month of life. He
      presented with a nodule 8 millimeters in diameter, tan-orange in color, ulcerated
      in the centre, located on the left corner of the left eye. A biopsy without total
      excision was performed. After the biopsy, the nodule enlarged to 1.5 cm in
      diameter and became haemorrhagic. The histologic evaluation and
      immunohistochemistry analysis resulted in the diagnosis of juvenile
      xanthogranuloma. For aesthetic reasons the nodule was removed by surgical
      resection. CONCLUSION: Juvenile xanthogranuloma is on a spectrum of histiocytic
      disorders, which is necessary to differentiate from maligniances in childhood by
      biopsy.

PMID- 24666807
TI  - Updating on the fungal composition in Sardinian sheep's milk by culture
      independent methods.
AB  - This work applies culture-independent methods for the characterization of fungal
      populations (yeasts and moulds) naturally occurring in Sardinian ewe's milk
      sampled in the Italian areas with the largest dairy production (Sardinia and
      Lazio regions). Sequences of the D1/D2 variable domains at the 5' end of the 26S
      rRNA gene were obtained by amplification of DNA directly isolated from milk, and
      this allowed identification of a total of 6 genera and 15 species of fungi. Among
      the 6 identified genera Geotrichum spp., Candida spp., Phaeosphaeriopsis spp.,
      Pestalotiopsis spp. and Cladosporium spp. belong to the phylum of Ascomycota,
      while Cryptococcus spp. is part of the phylum of Basidiomycota. In particular,
      two genera (Pestalotiopsis and Phaeosphaeriopsis) and two species
      (Plectosphaerella cucumerina and Pryceomyces carsonii) have never been reported
      in dairy ecosystems before. Results provide evidence that several moulds and
      yeasts, previously described only in ovine cheeses, are transferred directly from
      raw milk. The knowledge of fungal consortia inhabiting sheep raw milk is a
      particularly relevant issue because several species are directly involved in
      cheese making and ripening, determining the typical aroma. On the other hand,
      spoilage yeasts and moulds are involved in anomalous fermentation of cheese and
      may be responsible for considerable economic losses and serious risks for
      consumers' health. 

PMID- 24666808
TI  - Degree of conversion of resin-based materials cured with dual-peak or single-peak
      LED light-curing units.
AB  - BACKGROUND: There is a lack of data on polymerization of resin-based materials
      (RBMs) used in paediatric dentistry, using dual-peak light-emitting diode (LED)
      light-curing units (LCUs). OBJECTIVE: To evaluate the degree of conversion (DC)
      of RBMs cured with dual-peak or single-peak LED LCUs. METHODS: Samples of Vit-l
      escence (Ultradent) and Herculite XRV Ultra (Kerr) and fissure sealants Delton
      Clear and Delton Opaque (Dentsply) were prepared (n = 3 per group) and cured with
      either one of two dual-peak LCUs (bluephase((r)) G2; Ivoclar Vivadent or Valo;
      Ultradent) or a single-peak (bluephase((r)) ; Ivoclar Vivadent). High-performance
      liquid chromatography and nuclear magnetic resonance spectroscopy were used to
      confirm the presence or absence of initiators other than camphorquinone. The DC
      was determined using micro-Raman spectroscopy. Data were analysed using general
      linear model anova; alpha = 0.05. RESULTS: With Herculite XRV Ultra, the single
      peak LCU gave higher DC values than either of the two dual-peak LCUs (P < 0.05).
      Both fissure sealants showed higher DC compared with the two RBMs (P < 0.05); the
      DC at the bottom of the clear sealant was greater than the opaque sealant, (P <
      0.05). 2,4,6-trimethylbenzoyldiphenylphosphine oxide (Lucirin((r)) TPO) was found
      only in Vit-l-escence. CONCLUSIONS: Dual-peak LED LCUs may not be best suited for
      curing non-Lucirin((r)) TPO-containing materials. A clear sealant showed a better
      cure throughout the material and may be more appropriate than opaque versions in
      deep fissures.

PMID- 24666809
TI  - Twenty-four hour variation in heart rate variability indices derived from
      fractional differintegration.
AB  - Assuming that RR time-series behave as a fractionally differintegrated Gaussian
      process, Garcia-Gonzalez et al. (2003) recently proposed new indices for
      quantifying variability and structure in RR data. One of these was the
      'fractional noise quantifier' (fnQ), measuring the departure of an RR time-series
      from a monofractal structure (i.e. a measure of its multifractality). Sixty-nine
      participants (aged = 34.5 +/- 12.4 years, body mass index (BMI) = 23.9 +/- 2.9 kg
      m(-2) , maximal oxygen uptake rate (VO2peak ) = 42.4 +/- 10.9 ml min(-1)  kg(-1)
      , 39 males) provided continuous beat-to-beat ECG recordings for a 24-h period.
      Fractional differintegration was used to quantify fnQ, and heart rate variability
      was calculated in the time domain. All variables were evaluated during
      consecutive 1-h periods and also during four 6-h blocks corresponding to morning,
      afternoon, evening and night periods. Apart from RR, circadian trends in all
      variables were independent of gender (P = 0.11-0.59). Apart from fnQ, all
      variables exhibited circadian variation (0.0005<P<0.012). Although fnQ was
      statistically uniform during the 24-h period, it showed a trend towards elevated
      values during evening and night. The main finding of this study was that fnQ was
      elevated by around 10% during the evening and night, although this was not
      statistically significant. This suggests that the structure of RR time-series in
      healthy individuals is most strongly 'multifractal' during evening and night
      periods. fnQ appears to be a plausible surrogate measure of multifractality in RR
      time-series. 

PMID- 24666810
TI  - Reducing alcohol use among 9th grade students: 6 month outcomes of a brief, Web
      based intervention.
AB  - This study tested a brief, Web-based personalized feedback program aimed at
      reducing alcohol use and alcohol-related consequences among 9th grade students
      (N=513). Results indicated no differences between the control group and
      intervention group on either frequency of drinking or alcohol-related
      consequences at the 6-month follow-up. Reductions in alcohol use and the
      associated consequences found at the 3-month follow-up were not sustained across
      the academic year. Results indicate that brief, Web-based feedback programs may
      not be sufficient to provide a sustained impact on alcohol use and alcohol
      related consequences over time, suggesting either booster sessions or adjunctive
      interventions, such as parent-based interventions, may be warranted for this age
      group. 

PMID- 24666812
TI  - Attentional bias modification in smokers trying to quit: a longitudinal study
      about the effects of number of sessions.
AB  - Attentional bias modification (ABM) to avoid smoking-related cues is a
      potentially new intervention in addition to existing therapy to stop smoking. We
      examined immediate and long-term changes in attentional bias and treatment
      outcomes from multiple ABM sessions in 67 smokers trying to quit. After assessing
      attentional bias baseline, participants were randomly allocated to one of three
      training groups: three sessions of ABM (avoid 3); two sessions of placebo-ABM and
      one session of ABM (avoid 1); and three sessions of placebo-ABM (avoid 0). At
      baseline, all groups had similar positive attentional bias, which became negative
      at 24h post-training. After 1 month, avoid 1 and avoid 3 still exhibited negative
      attentional biases. Only avoid 3 maintained this effect at 6-month, but not at 12
      month assessments. ABM produced a long-lasting automatic and maintained avoidance
      to smoking-related cues which depended on number of sessions; however its effects
      on treatment outcomes are uncertain.

PMID- 24666792
TI  - Development of a definition for Rapid Progression (RP) of renal function in HIV
      positive persons: the D:A:D study.
AB  - BACKGROUND: No consensus exists on how to define abnormally rapid deterioration
      in renal function (Rapid Progression, RP). We developed an operational definition
      of RP in HIV-positive persons with baseline estimated glomerular filtration rate
      (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on
      Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. METHODS: Two
      definitions were evaluated; RP definition A: An average eGFR decline (slope) >=5
      ml/min/1.73 m2/year over four years of follow-up with >=3 eGFR measurements/year,
      last eGFR <90 ml/min/1.73 m2 and an absolute decline >=5 ml/min/1.73 m2/year in
      two consecutive years. RP definition B: An absolute annual decline >=5
      ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity
      analyses were performed considering two and three years' follow-up. The
      percentage with and without RP who went on to subsequently develop incident
      chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months
      apart) was calculated. RESULTS: 22,603 individuals had baseline eGFR >=90
      ml/min/1.73 m2. 108/3655 (3.0%) individuals with >=4 years' follow-up and >=3
      measurements/year experienced RP under definition A; similar proportions were
      observed when considering follow-up periods of three (n=195/6375; 3.1%) and two
      years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions
      experienced RP when considering two years (n=476/10756; 4.4%) instead of three
      (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition
      A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6%
      of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%);
      whereas for RP definition B, fewer RP individuals progressed to CKD. CONCLUSIONS:
      Our results suggest using three years' follow-up and at least two eGFR
      measurements per year is most appropriate for a RP definition, as it allows
      inclusion of a reasonable number of individuals and is associated with the known
      risk factors. The definition does not necessarily identify all those that
      progress to incident CKD, however, it can be used alongside other renal
      measurements to early identify and assess those at risk of developing CKD. Future
      analyses will use this definition to identify other risk factors for RP,
      including the role of antiretrovirals.

PMID- 24666813
TI  - Autoimmune response in children with dengue. Case reports.
AB  - Dengue is an infectious disease caused by the dengue virus (DV), which can
      progress to dengue hemorrhagic fever and dengue shock syndrome. DV causes the
      production of auto-antibodies against human cells. A variety of factors have been
      associated with macrophage activation syndrome, including infections, drugs and
      autoimmune pathologies (systemic lupus erythematosus, systemic onset juvenile
      idiopathic arthritis). We present three cases of patients that clinically
      developed an autoimmune response related to a DV infection. Our country currently
      has endemic cases of dengue, with hyperimmune responses. Therefore, the physician
      should consider this possibility in the presence of unusual conditions. 

PMID- 24666811
TI  - A preliminary, randomized trial of aerobic exercise for alcohol dependence.
AB  - Interventions targeting physical activity may be valuable as an adjunct to
      alcohol treatment, but have been relatively untested. In the current study,
      alcohol dependent, physically sedentary patients were randomized to: a 12-week
      moderate-intensity, group aerobic exercise intervention (AE; n=25) or a brief
      advice to exercise intervention (BA-E; n=23). Results showed that individuals in
      AE reported significantly fewer drinking and heavy drinking days, relative to BA
      E during treatment. Furthermore adherence to AE strengthened the beneficial
      effect of intervention on alcohol use outcomes. While high levels of moderate
      intensity exercise appeared to facilitate alcohol recovery regardless of
      intervention arm, attending the group-based AE intervention seemed to further
      enhance the positive effects of exercise on alcohol use. Study findings indicate
      that a moderate intensity, group aerobic exercise intervention is an efficacious
      adjunct to alcohol treatment. Improving adherence to the intervention may enhance
      its beneficial effects on alcohol use. 

PMID- 24666815
TI  - Differences in nursing practice environment among US acute care unit types: a
      descriptive study.
AB  - BACKGROUND: The hospital nursing practice environment has been found to be
      crucial for better nurse and patient outcomes. Yet little is known about the
      professional nursing practice environment at the unit level where nurses provide
      24-hour bedside care to patients. OBJECTIVES: To examine differences in nursing
      practice environments among 11 unit types (critical care, step-down, medical,
      surgical, combined medical-surgical, obstetric, neonatal, pediatric, psychiatric,
      perioperative, and emergency) and by Magnet status overall, as well as four
      specific aspects of the practice environment. DESIGN: Cross-sectional study.
      SETTINGS: 5322 nursing units in 519 US acute care hospitals. METHODS: The nursing
      practice environment was measured by the Practice Environment Scale of the
      Nursing Work Index. The Practice Environment Scale of the Nursing Work Index mean
      composite and four subscale scores were computed at the unit level. Two
      statistical approaches (one-way analysis of covariance and multivariate analysis
      of covariance analysis) were employed with a Tukey-Kramer post hoc test. RESULTS:
      In general, the nursing practice environment was favorable in all unit types.
      There were significant differences in the nursing practice environment among the
      11 unit types and by Magnet status. Pediatric units had the most favorable
      practice environment and medical-surgical units had the least favorable. A
      consistent finding across all unit types except neonatal units was that the
      staffing and resource adequacy subscale scored the lowest compared with all other
      Practice Environment Scale of the Nursing Work Index subscales (nursing
      foundations for quality of care, nurse manager ability, leadership, and support,
      and nurse-physician relations). Unit nursing practice environments were more
      favorable in Magnet than non-Magnet hospitals. CONCLUSIONS: Findings indicate
      that there are significant variations in unit nursing practice environments among
      11 unit types and by hospital Magnet status. Both hospital-level and unit
      specific strategies should be considered to achieve an excellent nursing practice
      environment in all hospital units.

PMID- 24666816
TI  - Spirituality: Everyone has it, but what is it?
AB  - Spirituality has been the subject of discussion over many years, yet
      understanding its nature, and usefulness during illness, can be elusive. Nurses
      and other health-care practitioners can often be in the position to help patients
      discuss spiritual matters because of their direct contact on a frequent basis,
      but might not feel confident to do so because the subject can appear to be overly
      complex. This paper summarizes some of the essential elements of spirituality as
      synthesized from literature that refers to it. The literature draws attention to
      spirit as the core of a person's being, and the notion that spirituality
      comprises multiple dimensions that exist internally or become externally manifest
      through behaviours. The presence and use of spirituality can lead to such
      outcomes as peace of mind, self-fulfilment and alleviation of suffering.
      Underpinning all spirituality is the concept of transcendence where a person can
      be 'lifted up' above the challenges of illness. 

PMID- 24666814
TI  - Clinical features and outcomes of focal segmental glomerulosclerosis pathologic
      variants in Korean adult patients.
AB  - BACKGROUND: Many studies have shown that clinical characteristics and outcomes
      differ depending on pathologic variants of focal segmental glomerulosclerosis
      (FSGS). However, these are not well defined in Asian populations. METHODS: This
      retrospective study evaluated clinical features and outcomes of pathologic FSGS
      variants in 111 adult patients between January 2004 and December 2012. Primary
      outcome was the composite of doubling of baseline serum creatinine concentrations
      (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included
      complete (CR) or partial remission (PR). RESULTS: There were 70 (63.1%), 20
      (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified
      (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At
      presentation, nephrotic-range proteinuria occurred more commonly in tip lesion
      than in other variants. The overall 5-year renal survival rate was 76.8%. During
      a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion
      reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in
      perihilar and NOS variants, but this difference was not statistically significant
      in an adjusted Cox model. However, tip lesion was associated with a significantly
      increased probability of achieving CR (P = 0.044). CONCLUSION: Similar to other
      populations, Korean adult patients with FSGS have distinct clinical features with
      the exception of a rare frequency of cellular and collapsing variants. Although
      pathologic variants were not associated with overall outcome, the tip variant
      exhibited favorable outcome in terms of achieving remission. Further studies are
      required to delineate long-term outcome and response to treatment of the
      pathologic variants.

PMID- 24666817
TI  - Feasibility of an online and a face-to-face version of a self-management program
      for young adults with a rheumatic disease: experiences of young adults and peer
      leaders.
AB  - BACKGROUND: Based on the self-efficacy theory, an online and a face-to-face self
      management programs 'Challenge your Arthritis' for young adults with a rheumatic
      disease have recently been developed. These two courses are led by young peer
      leaders. The objective of this study was to test the feasibility of the online
      and face-to-face self-management program. METHODS: Feasibility was evaluated on
      items of perceived usefulness, perceived ease of use, user-acceptance, and
      adherence to both programs in young adults and peer leaders. Additional analyses
      of interactions on the e-Health applications, discussion board and chat board,
      were conducted. RESULTS: Twenty-two young adults with a diagnosed rheumatic
      disease participated in the study: 12 young adults followed the online program
      and 10 followed the face-to-face program. Both programs appeared to be feasible,
      especially in dealing with problems in daily life, and the participants indicated
      the time investment as 'worthwhile'. In using the online program, no technical
      problems occurred. Participants found the program easy to use, user friendly, and
      liked the 'look and feel' of the program. CONCLUSIONS: Both the online and the
      face-to-face versions of a self-management program. 'Challenge your arthritis'
      were found to be feasible and well appreciated by young adults with a rheumatic
      disease. Because these programs are likely to be a practical aid to health
      practices, a randomized controlled study to investigate the effects on patient
      outcomes is planned.

PMID- 24666818
TI  - Gait speed as a predictor of outcomes in post-acute transitional care for older
      people.
AB  - AIMS: Gait speed has been advocated as a marker of vulnerability, but its
      discriminatory utility and predictive ability in frail older people in a post
      acute community-based rehabilitation program has not been extensively
      investigated. The aims of this research were to examine whether there was a
      meaningful improvement in gait speed in post-acute care patients, and to
      determine whether gait speed predicted outcomes at 6-month follow up. METHODS: In
      a prospective cohort study, 351 older persons admitted to a transition care
      program were comprehensively assessed using the interRAI Home Care instrument.
      This included a timed 4-m walk at admission and discharge. A telephone interview
      6 months after admission determined functional independence, living status and
      readmissions to hospital. RESULTS: Mean (SD) gait speed was 0.34 m/s (0.21 m/s)
      at admission and 0.54 m/s (0.33 m/s) at discharge. The improvement in gait speed
      over the program was significant (P<0.001), and represents a clinically
      meaningful change. At 6 months postadmission to transition care, a majority of
      patients (86.9%) were living in the community and 40.5% had at least one
      readmission to hospital. Higher gait speed at admission was associated with
      increased likelihood of living in the community (OR 1.34, P=0.015) and being
      functionally independent (OR 1.19 P=0.017) at follow up, as well as a reduced
      risk of hospital readmissions (OR 1.18, P=0.006). CONCLUSIONS: Gait speed is an
      inexpensive, feasible and objective measure of physical performance in frail
      older people. It could be a useful tool in community-based transition care
      settings to predict outcomes.

PMID- 24666819
TI  - Endoplasmic reticulum stress is accompanied by activation of NF-kappaB in
      amyotrophic lateral sclerosis.
AB  - BACKGROUND: Recent studies have indicated that endoplasmic reticulum (ER) stress
      is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). ER stress
      occurs when the ER-mitochondria calcium cycle is disturbed and misfolded proteins
      accumulate in the ER. To cope with ER stress, cells activate the unfolded protein
      response (UPR). Accumulating evidence from non-neuronal cell models suggests that
      there is extensive cross-talk between the UPR and the NF-kappaB pathway. METHODS:
      Here we investigated the expression of NF-kappaB and the main UPR markers X-box
      binding protein 1 (XBP1), basic leucine-zipper transcription factor 6 (ATF6) and
      phosphorylated eukaryotic initiation factor-2alpha (p-eIF2) in mutated SOD1(G93A)
      cell models of ALS, as well as their modulation by lipopolysaccharide and ER
      stressing (tunicamycin) stimuli. RESULTS: Expression of NF-kappaB was enhanced in
      the presence of SOD1(G93A). Lipopolysaccharide did not induce the UPR in NSC34
      cells and motor neurons in a mixed motor neuron-glia coculture system. The
      induction of the UPR by tunicamycin was accompanied by activation of NF-kappaB in
      NSC34 cells and motor neurons. CONCLUSION: Our data linked two important
      pathogenic mechanisms of ALS, ER stress and NF-kappaB signalling, in motor
      neurons.

PMID- 24666821
TI  - Diagnosing irritable bowel syndrome with a combination of biomarkers and
      "psychomarkers".

PMID- 24666820
TI  - High coffee consumption and different brewing methods in relation to
      postmenopausal endometrial cancer risk in the Norwegian women and cancer study: a
      population-based prospective study.
AB  - BACKGROUND: Coffee and its compounds have been proposed to inhibit endometrial
      carcinogenesis. Studies in the Norwegian population can be especially interesting
      due to the high coffee consumption and increasing incidence of endometrial cancer
      in the country. METHODS: A total of 97 926 postmenopausal Norwegian women from
      the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were
      included in the present analysis. We evaluated the general association between
      total coffee consumption and endometrial cancer risk as well as the possible
      impact of brewing method. Multivariate Cox regression analysis was used to
      estimate risks, and heterogeneity tests were performed to compare brewing
      methods. RESULTS: During an average of 10.9 years of follow-up, 462 incident
      endometrial cancer cases were identified. After multivariate adjustment,
      significant risk reduction was found among participants who drank >=8 cups/day of
      coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79).
      However, we did not observe a significant dose-response relationship. No
      significant heterogeneity in risk was found when comparing filtered and boiled
      coffee brewing methods. A reduction in endometrial cancer risk was observed in
      subgroup analyses among participants who drank >=8 cups/day and had a body mass
      index >=25 kg/m2, and in current smokers. CONCLUSIONS: These data suggest that in
      this population with high coffee consumption, endometrial cancer risk decreases
      in women consuming >=8 cups/day, independent of brewing method.

PMID- 24666822
TI  - Predictive models for hepatocellular carcinoma.

PMID- 24666823
TI  - Response to empiric proton pump inhibitor therapy in patients with esophageal
      eosinophilia.

PMID- 24666824
TI  - Prognostic value of the neutrophil-to-lymphocyte ratio in patients with acute-on
      chronic liver failure.
AB  - OBJECTIVES: The neutrophil-to-lymphocyte ratio (NLR) is a novel inflammation
      index that has been shown to independently predict poor clinical outcomes. We
      aimed to evaluate the role of NLR in the prediction of 3-month mortality in
      patients with acute-on-chronic liver failure (AoCLF). METHODS: One hundred and
      twenty-seven patients, including 46 patients with chronic hepatitis B (CHB), 81
      with AoCLF and 58 healthy controls (HCs), were enrolled in the study. All
      patients were followed up for 4 months. The primary end-point was in-hospital
      mortality at the end of 90 days. A blood sample was collected for all subjects at
      admission to examine liver function, renal function, international normalised
      ratio, C-reactive protein and neutrophil and lymphocyte counts, and NLRs were
      calculated. A total of six clinical chemistry and biochemical variables were
      analysed for potential associations with outcomes using Cox proportional hazards
      and multiple regression models. RESULTS: Acute-on-chronic liver failure patients
      had significantly higher NLRs on admission compared with HCs and CHB patients
      (all p = 0.001). Patients with elevated NLRs were associated with increased
      severity of liver disease and 3-month mortality rates. According to multivariate
      analysis, only NLR was an independent predictor for mortality (p = 0.025).
      CONCLUSIONS: The NLR measured at admission can serve as an independent predictor
      for 3-month mortality rate in AoCLF patients.

PMID- 24666825
TI  - Homing trajectories and initial orientation in a Neotropical territorial frog,
      Allobates femoralis (Dendrobatidae).
AB  - INTRODUCTION: The ability to relocate home or breeding sites after experimental
      removal has been observed in several amphibians and the sensory basis of this
      behavior has been studied in some temperate-region species. However, the actual
      return trajectories have rarely been quantified in these studies and it remains
      unknown how different cues guide the homing behavior. Dendrobatidae (dart-poison
      frogs) exhibit some of the most complex spatial behaviors among amphibians, such
      as territoriality and tadpole transport. Recent data showed that Allobates
      femoralis, a frog with paternal tadpole transport, successfully returns to the
      home territories after experimental translocations of up to 400 m. In the present
      study, we used harmonic direction finding to obtain homing trajectories.
      Additionally, we quantified the initial orientation of individuals, translocated
      10 m to 105 m, in an arena assay. RESULTS: Tracking experiments revealed that
      homing trajectories are characterized by long periods of immobility (up to
      several days) and short periods (several hours) of rapid movement, closely
      fitting a straight line towards the home territory. In the arena assay, the frogs
      showed significant homeward orientation for translocation distances of 35 m to 70
      m but not for longer and shorter distances. CONCLUSIONS: Our results describe a
      very accurate homing behavior in male A. femoralis. The straightness of
      trajectories and initial homeward orientation suggest integration of learned
      landmarks providing a map position for translocated individuals. Future research
      should focus on the role of learning in homing behavior and the exact nature of
      cues being used.

PMID- 24666826
TI  - Half-molar sodium lactate infusion improves cardiac performance in acute heart
      failure: a pilot randomised controlled clinical trial.
AB  - INTRODUCTION: Acute heart failure (AHF) is characterized by inadequate cardiac
      output (CO), congestive symptoms, poor peripheral perfusion and end-organ
      dysfunction. Treatment often includes a combination of diuretics, oxygen,
      positive pressure ventilation, inotropes and vasodilators or vasopressors.
      Lactate is a marker of illness severity but is also an important metabolic
      substrate for the myocardium at rest and during stress. We tested the effects of
      half-molar sodium lactate infusion on cardiac performance in AHF. METHODS: We
      conducted a prospective, randomised, controlled, open-label, pilot clinical trial
      in 40 patients fulfilling two of the following three criteria for AHF: (1) left
      ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory
      failure of predominantly cardiac origin requiring mechanical ventilation and (3)
      currently receiving vasopressor and/or inotropic support. Patients in the
      intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the
      course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The
      control group received only a 3 ml/kg bolus of Hartmann's solution without
      continuous infusion. The primary outcome was CO assessed by transthoracic
      echocardiography 24 hours after randomisation. Secondary outcomes included a
      measure of right ventricular systolic function (tricuspid annular plane systolic
      excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters,
      along with length of stay and mortality. RESULTS: The infusion of half-molar
      sodium lactate increased (mean +/- SD) CO from 4.05 +/- 1.37 L/min to 5.49 +/-
      1.9 L/min (P < 0.01) and TAPSE from 14.7 +/- 5.5 mm to 18.3 +/- 7 mm (P = 0.02).
      Plasma sodium and pH increased (136 +/- 4 to 146 +/- 6 and 7.40 +/- 0.06 to 7.53
      +/- 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate
      levels decreased. There were no significant differences in the need for
      vasoactive therapy, respiratory support, renal or liver function tests, duration
      of ICU and hospital stay or 28- and 90-day mortality. CONCLUSIONS: Infusion of
      half-molar sodium lactate improved cardiac performance and led to metabolic
      alkalosis in AHF patients without any detrimental effects on organ function.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT01981655. Registered 13 August 2013.

PMID- 24666827
TI  - APUM5, encoding a Pumilio RNA binding protein, negatively regulates abiotic
      stress responsive gene expression.
AB  - BACKGROUND: A mutant screening was carried out previously to look for new genes
      related to the Cucumber mosaic virus infection response in Arabidopsis. A Pumilio
      RNA binding protein-coding gene, Arabidopsis Pumilio RNA binding protein 5
      (APUM5), was obtained from this screening. RESULTS: APUM5 transcriptional
      profiling was carried out using a bioinformatics tool. We found that APUM5 was
      associated with both biotic and abiotic stress responses. However, bacterial and
      fungal pathogen infection susceptibility was not changed in APUM5 transgenic
      plants compared to that in wild type plants although APUM5 expression was induced
      upon pathogen infection. In contrast, APUM5 was involved in the abiotic stress
      response. 35S-APUM5 transgenic plants showed hypersensitive phenotypes under salt
      and drought stresses during germination, primary root elongation at the seedling
      stage, and at the vegetative stage in soil. We also showed that some abiotic
      stress-responsive genes were negatively regulated in 35S-APUM5 transgenic plants.
      The APUM5-Pumilio homology domain (PHD) protein bound to the 3' untranslated
      region (UTR) of the abiotic stress-responsive genes which contained putative
      Pumilio RNA binding motifs at the 3' UTR. CONCLUSIONS: These results suggest that
      APUM5 may be a new post-transcriptional regulator of the abiotic stress response
      by direct binding of target genes 3' UTRs.

PMID- 24666830
TI  - Bile acid aspiration associated with lung chemical profile linked to other
      biomarkers of injury after lung transplantation.
AB  - Aspiration of gastrointestinal contents has been linked to worse outcomes
      following lung transplantation but uncertainty exists about underlying
      mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage
      fluid (BALF) in patients with episodic aspiration (defined by bile acids in the
      BALF) to identify potential metabolic changes associated with aspiration. Paired
      samples, one with bile acids and another without, from 29 stable lung transplant
      patients were studied. Liquid chromatography coupled to high-resolution mass
      spectroscopy was used to interrogate metabolomic contents of these samples. Data
      were obtained for 7068 ions representing intermediary metabolites, environmental
      agents and chemicals associated with microbial colonization. A substantial number
      (2302) differed between bile acid positive and negative samples when analyzed by
      false discovery rate at q = 0.01. These included pathways associated with
      microbial metabolism. Hierarchical cluster analysis defined clusters of chemicals
      associated with bile acid aspiration that were correlated to previously reported
      biomarkers of lung injury including T cell granzyme B level and the
      chemoattractants CXCL9 and CXCL10. These data specifically link bile acids
      presence in lung allografts to inflammatory pathways known to segregate with
      worsening allograft outcome, and provide additional mechanistic insight into the
      association between reflux and lung allograft injury.

PMID- 24666831
TI  - Antibody desensitization therapy in highly sensitized lung transplant candidates.
AB  - As HLAs antibody detection technology has evolved, there is now detailed HLA
      antibody information available on prospective transplant recipients. Determining
      single antigen antibody specificity allows for a calculated panel reactive
      antibodies (cPRA) value, providing an estimate of the effective donor pool. For
      broadly sensitized lung transplant candidates (cPRA >= 80%), our center adopted a
      pretransplant multi-modal desensitization protocol in an effort to decrease the
      cPRA and expand the donor pool. This desensitization protocol included
      plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19
      days followed by intravenous immunoglobulin. Eight of 18 candidates completed
      therapy with the primary reasons for early discontinuation being transplant (by
      avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis,
      there were no significant changes in PRA or cPRA changes over time with the
      protocol. A sub-analysis of the median fluorescence intensity (MFI) change
      indicated a small decline that was significant in antibodies with MFI 5000
      10,000. Nine of 18 candidates subsequently had a transplant. Posttransplant
      survival in these nine recipients was comparable to other pretransplant
      sensitized recipients who did not receive therapy. In summary, an aggressive
      multi-modal desensitization protocol does not significantly reduce pretransplant
      HLA antibodies in a broadly sensitized lung transplant candidate cohort.

PMID- 24666833
TI  - Advisory committee on immunization practices recommended immunization schedules
      for persons aged 0 through 18 years-United States, 2014.

PMID- 24666832
TI  - Adapted treatment of Epstein-Barr virus infection to prevent posttransplant
      lymphoproliferative disorder after heart transplantation.
AB  - Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur
      within 1 year of transplantation, and over 50% are associated with Epstein-Barr
      virus (EBV). EBV primary infection and reactivation are PTLD predictive factors,
      but there is no consensus for their treatment. We conducted a prospective single
      center study on 299 consecutive heart-transplant patients treated with the same
      immunosuppressive regimen and monitored by repetitive EBV viral-load measurements
      and endomyocardial biopsies to detect graft rejection. Immunosuppression was
      tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary
      infection. In the absence of response at 1 month or a viral load >10(6)
      copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients
      responded to treatment without increased graft rejection. One primary infection
      case developed a possible PTLD, which completely responded to diminution of
      immunosuppression, and one patient, whose EBV load was unevaluable, died of
      respiratory complications secondary to PTLD. Compared with a historical cohort of
      820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol
      analysis. This is the largest study on EBV primary infection/reactivation
      treatment, the first using rituximab following solid organ transplantation to
      prevent PTLD and the first to demonstrate an acceptable tolerability profile in
      this setting.

PMID- 24666834
TI  - Persistent shortness of breath in a kidney transplant recipient.

PMID- 24666835
TI  - Adjunctive glucocorticoid therapy for non-HIV-related pneumocystis carinii
      pneumonia (NH-PCP).

PMID- 24666836
TI  - Extracellular matrix is modulated in advanced glycation end products milieu via a
      RAGE receptor dependent pathway boosted by transforming growth factor-beta1 RAGE.
AB  - BACKGROUND: Interstitial fibrosis is induced by imbalances in extracellular
      matrix homeostasis. Advanced glycation end products (AGEs) can bind and activate
      the receptor for AGEs (RAGE), which is involved in diabetic nephropathy. We set
      out to identify the role of AGEs in producing alterations leading to matrix
      hypertrophy and the pathway through which aminoguanidine, as well as anti-RAGE
      and anti-transforming growth factor (TGF)-beta1 antibody treatments could prevent
      these modifications. METHODS: Human embryonic kidney (HEK-293) cells were exposed
      to glycated bovine serum albumin (AGE-BSA) and co-treated with neutralizing
      antibodies or aminoguanidine. The effects on the transcriptional and
      translational levels of RAGE, TGF-beta1 and collagen IV were evaluated, while
      metalloproteinase activity was assessed by gelatin zymography. RESULTS: AGE-BSA
      (200 MUg/mL) upregulated RAGE's expression, while TGF-beta1 synthesis and the
      formation of its bioactive form were increased in a dose-dependent manner by
      AGEs. AGE-BSA exposure increased both matrix metalloproteinase (MMP) activity and
      collagen IV synthesis, boosted by TGF-beta1 upregulation. Aminoguanidine's
      effects revealed that small concentrations (10 MUmol/L) enhance AGE-BSA effects,
      by increasing the expression of RAGE and TGF-beta1, while higher concentrations
      (100 MUmol/L) contribute to their downregulation. CONCLUSIONS: Although AGEs
      regulate RAGE and TGF-beta1 by distinct pathways, RAGE activation leads to a
      further increase of TGF-beta1 levels. MMP-2 activity seems to rely on TGF-beta1,
      while MMP-9 was dependent on RAGE. These factors converge to control collagen IV
      turnover. Furthermore, although the antibody treatments might appear more
      efficient than AG in decreasing collagen IV levels, the cells compensate the RAGE
      and TGF-beta1 blockade by increasing the mRNA expression of these proteins.

PMID- 24666837
TI  - Is dexmedetomidine superior to midazolam as a premedication in children? A meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: In the current published literature, there are controversial results
      regarding the effectiveness of dexmedetomidine compared with midazolam as
      premedication in children. The aim of this meta-analysis was to compare the use
      of dexmedetomidine as a premedication in pediatric patients with that of
      midazolam. METHODS: We searched for articles published in English that matched
      the key words 'dexmedetomidine', 'midazolam', and 'children' in the PubMed,
      Cochrane Library, Ovid, and Google Scholar databases. Additional studies were
      identified from the reference lists of the retrieved articles. Only prospective
      randomized controlled trials (RCTs) that compared the use of dexmedetomidine and
      midazolam as premedications in children were included. The extraction of data
      from the articles was performed independently by two authors using a predesigned
      Excel spreadsheet. The relative risks (RRs), weighted mean differences (WMDs),
      and their corresponding 95% confidence intervals (95% CIs) were calculated for
      dichotomous and continuous outcome data using the quality effects model of the
      MetaXL version 1.3 software. RESULTS: Eleven prospective RCTs (829 children) met
      our criteria. Compared with midazolam, dexmedetomidine premedication was
      associated with more satisfactory sedation upon parent separation (eight RCTs
      [679 children]; RR: 1.25; 95% CI: 1.06, 1.46) and upon mask acceptance (seven
      RCTs [559 children]; RR: 1.17; 95% CI: 1.01, 1.36). During the postoperative
      period, premedication with dexmedetomidine lowered the numbers of requests for
      rescue analgesia (six RCTs [477 children]; RR: 0.55; 95% CI: 0.40, 0.74) and
      lowered the risks of agitation or delirium (seven RCTs with [466 children]; RR:
      0.59; 95% CI: 0.40, 0.88), and shivering (three RCTs [192 children]; RR: 0.33;
      95% CI: 0.18, 0.61). However, dexmedetomidine premedication reduced systolic
      blood pressure (three RCTs [242 children]; WMD: -11.47 mm.Hg(-1) ; 95% CI: 
      13.95, -8.98), mean blood pressure (three RCTs [202 children]; WMD: -5.66 mm.Hg(
      1) ; 95% CI: -8.89, -2.43), and heart rate (six RCTs [444 children]; WMD: -12.71
      beat.min(-1) ; 95% CI: -14.80, -10.62), and prolonged the onset of sedation (two
      RCTs [132 children] WMD: 13.78 min; 95% CI: 11.33, 16.23; I(2) = 0%) relative to
      midazolam. CONCLUSION: This meta-analysis demonstrated that dexmedetomidine
      premedication is superior to midazolam premedication in terms of producing
      satisfactory sedation upon parent separation and mask acceptance. Dexmedetomidine
      premedication provides clinical benefits that included reducing the requirements
      for rescue analgesia and reducing agitation or delirium and shivering during the
      postoperative period. However, the risks of heart rate and blood pressure
      decreases, and the prolonged onset of sedation associated with dexmedetomidine
      should be considered.

PMID- 24666838
TI  - Biphasic modulation of cancer stem cell-driven solid tumour dynamics in response
      to reactivated replicative senescence.
AB  - OBJECTIVES: Cell senescence is a physiological programme of irreversible mitotic
      arrest that is triggered after a variety of intracellular and extracellular
      events. Its purpose is to protect tissue integrity by disabling mitosis in
      stressed or damaged cells. The senescence program serves as a tumour suppressor,
      and cancer cells are believed to bypass senescence to advance to malignancy.
      Recent studies have shown that senescence can be reactivated in cancer cells
      through a number of external perturbations, including oncogene activation, tumour
      suppressor gene withdrawal and irradiation. MATERIALS AND METHODS: We have
      developed an agent-based model of solid tumour growth whose input population
      composition is based on the cancer stem-cell hypothesis. It is used to show how
      cancer stem cells can drive tumour progression, while non-stem cancer cells (CCs)
      interfere with this by impeding cancer stem-cell dynamics. RESULTS: Here we show
      that intratumoural competition between the two cell types may arise to modulate
      tumour progression and ultimately cancer presentation risk. Model simulations
      reveal that reactivation of the replicative senescence programme in CCs initially
      increases total tumour burden, as attrition from cell death is partially averted,
      but evolves to provide tumour control in the long-term through increasing
      constraints on stem-cell compartment kinetics. CONCLUSIONS: Reactivation of
      replicative senescence can prolong CC competition with cancer stem cells, thereby
      ultimately inhibiting malignant progression regardless of tumour size.

PMID- 24666839
TI  - Prospective study of diagnostic accuracy comparing prostate cancer detection by
      transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with
      subsequent MR-guided biopsy in men without previous prostate biopsies.
AB  - BACKGROUND: The current diagnosis of prostate cancer (PCa) uses transrectal
      ultrasound-guided biopsy (TRUSGB). TRUSGB leads to sampling errors causing
      delayed diagnosis, overdetection of indolent PCa, and misclassification. Advances
      in multiparametric magnetic resonance imaging (mpMRI) suggest that imaging and
      selective magnetic resonance (MR)-guided biopsy (MRGB) may be superior to TRUSGB.
      OBJECTIVE: To compare the diagnostic efficacy of the magnetic resonance imaging
      (MRI) pathway with TRUSGB. DESIGN, SETTING, AND PARTICIPANTS: A total of 223
      consecutive biopsy-naive men referred to a urologist with elevated prostate
      specific antigen participated in a single-institution, prospective, investigator
      blinded, diagnostic study from July 2012 through January 2013. INTERVENTION: All
      participants had mpMRI and TRUSGB. Men with equivocal or suspicious lesions on
      mpMRI also underwent MRGB. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The
      primary outcome was PCa detection. Secondary outcomes were histopathologic
      details of biopsy and radical prostatectomy specimens, adverse events, and MRI
      reader performance. Sensitivity, specificity, negative predictive values (NPVs),
      and positive predictive values were estimated and basic statistics presented by
      number (percentage) or median (interquartile range). RESULTS AND LIMITATIONS: Of
      223 men, 142 (63.7%) had PCa. TRUSGB detected 126 cases of PCa in 223 men (56.5%)
      including 47 (37.3%) classed as low risk. MRGB detected 99 cases of PCa in 142
      men (69.7%) with equivocal or suspicious mpMRI, of which 6 (6.1%) were low risk.
      The MRGB pathway reduced the need for biopsy by 51%, decreased the diagnosis of
      low-risk PCa by 89.4%, and increased the detection of intermediate/high-risk PCa
      by 17.7%. The estimated NPVs of TRUSGB and MRGB for intermediate/high-risk
      disease were 71.9% and 96.9%, respectively. The main limitation is the lack of
      long follow-up. CONCLUSIONS: We found that mpMRI/MRGB reduces the detection of
      low-risk PCa and reduces the number of men requiring biopsy while improving the
      overall rate of detection of intermediate/high-risk PCa. PATIENT SUMMARY: We
      compared the results of standard prostate biopsies with a magnetic resonance (MR)
      image-based targeted biopsy diagnostic pathway in men with elevated prostate
      specific antigen. Our results suggest patient benefits of the MR pathway. Follow
      up of negative investigations is required.

PMID- 24666840
TI  - Zometa European Study (ZEUS): another failed crusade for the holy grail of
      prostate cancer bone metastases prevention?

PMID- 24666841
TI  - Myocardial hydrophilic polymer emboli following cardiac catheterization: a case
      report and literature review.
AB  - BACKGROUND: Intravascular polymer emboli have been reported in the skin, lungs,
      and brain following vascular procedures utilizing hydrophilic polymer coated
      devices. The Cook arterial introducer sheath was the first of these devices to be
      introduced, after which case reports followed documenting sterile inflammation at
      the sheath access site, characterized histologically by perivascular granulomas
      containing hydrophilic polymer. More recently, hydrophilic polymer emboli have
      been reported in the vessels of the lungs and brain in association with ischemia
      and infarct following vascular procedures using polymer coated devices. METHODS:
      We report a case of intravascular myocardial emboli associated with acute
      myocardial infarction following cardiac catheterization. The patient was a 65
      year-old man who received cardiac catheterization with placement of a bare metal
      stent following myocardial infarction. One month later, the patient presented
      with angina and died shortly after admission. RESULTS: Autopsy revealed
      hemopericardium with rupture of the left ventricle through an aneurismal defect
      within the area of prior infarction. Microscopically, an area of acute infarction
      was present within the aneurismal defect. Numerous small and medium-sized vessels
      within the left ventricle were occluded by basophilic amorphous granular material
      with an inflammatory giant cell response. CONCLUSION: The emboli were most
      frequent in the area of acute infarction, suggesting that the emboli may have
      resulted in ischemia leading to the patient's death. This is the third documented
      case of intramyocardial polymer emboli following cardiac catheterization and the
      first case to our knowledge to document an association between intravascular
      myocardial polymer emboli and acute myocardial infarction.

PMID- 24666843
TI  - Right heart failure: what etiology?

PMID- 24666842
TI  - Use of cheese whey for biomass production and spray drying of probiotic
      lactobacilli.
AB  - The double use of cheese whey (culture medium and thermoprotectant for spray
      drying of lactobacilli) was explored in this study for adding value to this
      wastewater. In-house formulated broth (similar to MRS) and dairy media (cheese
      and ricotta whey and whey permeate) were assessed for their capacity to produce
      biomass of Lactobacillus paracasei JP1, Lb. rhamnosus 64 and Lb. gasseri 37.
      Simultaneously, spray drying of cheese whey-starch solution (without lactobacilli
      cells) was optimised using surface response methodology. Cell suspensions of the
      lactobacilli, produced in in house-formulated broth, were spray-dried in cheese
      whey-starch solution and viability monitored throughout the storage of powders
      for 2 months. Lb. rhamnosus 64 was able to grow satisfactorily in at least two of
      the in-house formulated culture media and in the dairy media assessed. It also
      performed well in spray drying. The performance of the other strains was less
      satisfactory. The growth capacity, the resistance to spray drying in cheese whey
      starch solution and the negligible lost in viability during the storage (2
      months), makes Lb. rhamnosus 64 a promising candidate for further technological
      studies for developing a probiotic dehydrated culture for foods, utilising
      wastewaters of the dairy industry (as growth substrate and protectant) and spray
      drying (a low-cost widely-available technology). 

PMID- 24666844
TI  - Identification and survival studies of Mycobacterium tuberculosis within
      Laboratory-Fermented bovine milk.
AB  - BACKGROUND: Mycobacterium tuberculosis and Mycobacterium bovis are the classic
      agents causing tuberculosis (TB) in humans and animals respectively. Transmission
      of tuberculous bacteria to humans usually occurs by inhalation of aerosols
      containing droplets of tubercle bacilli or via consumption of contaminated foods
      and drinks, primarily milk. The practice of milk pooling, including from cows
      with TB of the udder, further exacerbates the situation by rendering the whole
      milk supply infective. The simultaneous presence of indigenous lactic acid
      bacteria (LAB) in Mycobacterium-contaminated milk is believed to confer
      protective effect when the milk is adequately fermented. This study assessed the
      effect of LAB on the viability of mycobacteria in inherently contaminated pool of
      raw milk during fermentation as a function of time. FINDINGS: Growth was obtained
      in the pooled raw milk culture, and identified to be M. tuberculosis. This M.
      tuberculosis growth was undetectable in the milk culture by day 7 as assessed by
      plating serial dilutions of the milk culture for up to 14 days. CONCLUSIONS: Some
      LAB species appear to show inhibitory effect on tubercle bacilli. If proven by
      more rigorous, controlled experimental results regarding such effect, selected
      LAB (with proven safety and efficacy) may have potential applications as anti
      mycobacterial agents.

PMID- 24666845
TI  - Effect of nitrogen atomic percentage on N+-bombarded MWCNTs in cytocompatibility
      and hemocompatibility.
AB  - N+-bombarded multi-walled carbon nanotubes (N+-bombarded MWCNTs), with different
      nitrogen atomic percentages, were achieved by different N ion beam currents using
      ion beam-assisted deposition (IBAD) on MWCNTs synthesized by chemical vapor
      deposition (CVD). Characterizations of N+-bombarded MWCNTs were evaluated by X
      ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM),
      Raman spectroscopy, and contact angle. For comparison, the in vitro
      cytocompatibility of the N+-bombarded MWCNTs with different N atomic percentages
      was assessed by cellular adhesion investigation using human endothelial cells
      (EAHY926) and mouse fibroblast cells (L929), respectively. The results showed
      that the presence of nitrogen in MWCNTs accelerated cell growth and proliferation
      of cell culture. The higher nitrogen content of N+-bombarded MWCNTs, the better
      cytocompatibility. In addition, N+-bombarded MWCNTs with higher N atomic
      percentage displayed lower platelet adhesion rate. No hemolysis can be observed
      on the surfaces. These results proved that higher N atomic percentage led N+
      bombarded MWCNTs to better hemocompatibility. 

PMID- 24666847
TI  - Tube banding to correct steal syndrome after arteriovenous fistula construction
      for hemodialysis.

PMID- 24666848
TI  - A minimally invasive novel repair of a combined organo-mesenteraxial volvulus.

PMID- 24666846
TI  - Systematic literature review and validity evaluation of the Expanded Disability
      Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in
      patients with multiple sclerosis.
AB  - BACKGROUND: There are a number of instruments that describe severity and
      progression of multiple sclerosis and they are increasingly used as endpoints to
      assess the effectiveness of therapeutic interventions. We examined to what extent
      the psychometric properties of two accepted instruments--EDSS and MSFC--meet
      methodological standards and the value they have in clinical trials. METHODS: We
      conducted a systematic literature search in relevant databases [MEDLINE (PubMed),
      ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results.
      Relevant full-text publications were identified using abstract and then full-text
      reviews, and the literature was reviewed. RESULTS: For evaluation of psychometric
      properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120
      relevant full-text publications were identified, 54 of them assessed the EDSS, 26
      the MSFC and 40 included both instruments. The EDSS has some documented
      weaknesses in reliability and sensitivity to change. The main limitations of the
      MSFC are learning effects and the z-scores method used to calculate the total
      score. However, the methodological criterion of validity applies sufficiently for
      both instruments.For use in clinical studies, we found the EDSS to be preferred
      as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC).
      CONCLUSIONS: Recognizing their strengths and weaknesses, both EDSS and MSFC are
      suitable to detect the effectiveness of clinical interventions and to monitor
      disease progression. Almost all publications identify the EDSS as the most widely
      used tool to measure disease outcomes in clinical trials. Despite some
      limitations, both instruments are accepted as endpoints and neither are discussed
      as surrogate parameters in identified publications. A great advantage of the EDSS
      is its international acceptance (e.g. by EMA) as a primary endpoint in clinical
      trials and its broad use in trials, enabling cross-study comparisons.

PMID- 24666849
TI  - Surgical treatment in drug body packers.

PMID- 24666851
TI  - Granulomatous mastitis: presentation, treatment, and outcome.

PMID- 24666850
TI  - DeBakey type II aortic dissection: a rare catastrophic complication of pregnancy.

PMID- 24666852
TI  - Intracystic papillary carcinoma of the breast in a male patient.

PMID- 24666853
TI  - Mucinous cystadenoma of the mesorectum.

PMID- 24666854
TI  - Cholangitis resulting from a fragmented plastic biliary stent.

PMID- 24666855
TI  - The 'mature' acute care model.

PMID- 24666856
TI  - Acute tracheal tear: an open and shut case?

PMID- 24666857
TI  - Phytobezoar within Meckel's diverticulum: an unusual cause of intestinal
      obstruction.

PMID- 24666858
TI  - Broadly reactive anti-HLA antibodies after a single unit transfusion with
      nonleukoreduced red blood cells.

PMID- 24666859
TI  - The clinical characteristics of surgical diseases among patients with HIV/AIDS.

PMID- 24666860
TI  - Defining new directions for more effective management of surgical pain in the
      United States: highlights of the inaugural Surgical Pain CongressTM.
AB  - Despite advances in pharmacologic options for the management of surgical pain,
      there appears to have been little or no overall improvement over the last two
      decades in the level of pain experienced by patients. The importance of adequate
      and effective surgical pain management, however, is clear, because inadequate
      pain control 1) has a wide range of undesirable physiologic and immunologic
      effects; 2) is associated with poor surgical outcomes; 3) has increased
      probability of readmission; and 4) adversely affects the overall cost of care as
      well as patient satisfaction. There is a clear unmet need for a national surgical
      pain management consensus task force to raise awareness and develop best practice
      guidelines for improving surgical pain management, patient safety, patient
      satisfaction, rapid postsurgical recovery, and health economic outcomes. To
      comprehensively address this need, the multidisciplinary Surgical Pain CongressTM
      has been established. The inaugural meeting of this Congress (March 8 to 10,
      2013, Celebration, Florida) evaluated the current surgical pain management
      paradigm and identified key components of best practices. 

PMID- 24666861
TI  - Mary H. Gibbon: teamwork of the heart.

PMID- 24666862
TI  - Radiofrequency ablation as first-line treatment of varicose veins.
AB  - Endovascular radiofrequency ablation is a minimally invasive method to safely
      treat symptomatic refluxing varicose veins. A retrospective chart review was used
      to determine patient demographics, disease severity, treatment algorithm, and
      outcome in patients who underwent radiofrequency ablation of symptomatic
      refluxing veins that had failed conservative management. Statistical analysis was
      done using GraphPad Demo Version (San Diego, CA). Two hundred forty-one limbs in
      179 patients (average age, 53 years; 73% females, 27% males) were treated.
      Preprocedure Clinical Etiological Anatomic and Pathologic (CEAP) scores were C2s:
      236, C3s: 4, and C5s:1. Procedures were performed in the office using tumescent
      anesthetic; all patients could ambulate immediately after the procedure.
      Postprocedure total occlusion (TO) rate was seen in 93 per cent of limbs (223
      limbs) at 3 months and 91 per cent of limbs (220 limbs) at 12 months
      posttreatment. No relationship was found between patients who did not have total
      occlusion and age, sex, diameter of veins, CEAP scores, preoperative reflux time,
      and volume of tumescent anesthetic (P > 0.05). The VNUS procedure is an in
      office, minimally invasive procedure with a low complication rate and quick
      recovery. Total occlusion rates are high and there is improvement in disease
      severity after treatment. 

PMID- 24666863
TI  - Selective hepatic vascular exclusion versus pringle maneuver in partial
      hepatectomy for liver hemangioma compressing or involving the major hepatic
      veins.
AB  - Massive blood loss remains a problem during resection for giant liver hemangioma.
      This present study was designed to compare selective hepatic vascular exclusion
      (SHVE) versus Pringle maneuver in surgery for liver hemangioma compressing the
      major (right, middle, or left) hepatic veins. From January 2003 to December 2011,
      589 consecutive patients with hemangioma underwent liver resection in our
      department, and 273 patients had their tumors compressing at least one of the
      three major hepatic veins (right, middle, or left). Either SHVE (n = 120
      patients) or Pringle maneuver (n = 153 patients) was used to minimize blood loss
      during resection. Data regarding the intraoperative and postoperative courses of
      these patients were retrospectively analyzed. There was no significant difference
      between the two groups of patients regarding age, sex, tumor size, types of
      hepatectomy, and extent of tumor involvement of the major hepatic veins.
      Intraoperative blood loss, transfusion requirements, and transfusion volume were
      significantly less in the SHVE group (P < 0.01). For the Pringle group, major
      hepatic veins were lacerated in 19 patients during hepatic parenchymal
      transection. For the SHVE group, a major hepatic vein was lacerated during
      extrahepatic dissection of the hepatic vein in two patients and during hepatic
      parenchymal transection in 14 patients. SHVE was more efficacious in minimizing
      intraoperative bleeding during liver resection for hemangiomas compressing the
      major hepatic veins. It prevented intraoperative major bleeding and air embolism
      and significantly decreased postoperative liver failure and in-hospital
      mortality. 

PMID- 24666864
TI  - The efficacy and morbidity of different surgical treatment techniques for chronic
      anal fissure: an academic colorectal experience.
AB  - Up to 40 per cent of chronic fissures will fail to heal with medical treatment
      alone. Open (OLIS) and closed (CLIS) lateral internal sphincterotomies are
      considered by many to be the treatment of choice for chronic anal fissures (CAF).
      The aim of this study was to compare the efficacy and clinical outcomes of
      different surgical techniques for treatment of CAF. We performed a retrospective
      chart review of 387 patients with CAF who underwent surgical intervention
      performed by colorectal surgeons between 2006 and 2012 at Greenville Hospital
      System. Of 387 patients, 199 underwent OLIS, 124 CLIS, and 64 patients underwent
      fissurectomy alone (FE). We investigated the effect of the surgical technique on
      time of healing, rate of flatus incontinence, wound infection, recurrence, and
      the need for additional intervention. There was no statistically significant
      difference among patients undergoing OLIS, CLIS, and FE in demographic
      characteristic, time of healing, rate of wound infections, and fecal continence,
      or recurrence rate. Comparison of a combined lateral internal sphincterotomy
      (LIS) group with FE showed that there is similar time of healing (P = 0.58), no
      statistical difference in flatus incontinence rate (P = 0.61), urinary retention
      (P = 1.0), fissure recurrence (P = 0.11), and prolonged healing (P = 0.2).
      Patients in FE group more likely required additional treatment to complete wound
      healing (P = 0.02). LIS is a safe and effective technique for treatment of CAF.
      Although there was no difference in complications rate and healing time, patients
      in the FE group required additional surgical or medical treatment more frequently
      to achieve complete healing. 

PMID- 24666865
TI  - Watchful waiting for ventral hernias: a longitudinal study.
AB  - Ventral hernias are a common clinical problem. Immediate repair is recommended
      for most ventral hernias despite significant recurrence rates. This practice may
      be related to a lack of understanding of the natural history of ventral hernias.
      The purpose of this study was to determine the natural history of ventral hernias
      and to determine if watchful waiting is an acceptable and safe option. Forty-one
      patients with ventral hernias were enrolled in a longitudinal cohort study of
      watchful waiting. Primary outcomes were functional impairment resulting from
      hernia disease as measured by the Activities Assessment Scale (AAS) and changes
      from baseline to two years in the physical and mental component score of the SF
      36 Health Survey. Secondary outcomes included complications such as
      incarceration. Mixed-effects model for repeated measures and Student's t tests
      were used to evaluate scale performance. The mean age of enrollees was 64 years,
      and the mean hernia size was 239 cm(2). Eleven patients were lost to follow-up,
      and seven patients died of other causes. All remaining patients were followed for
      two years. There was one incarceration during the follow-up period. There was no
      deterioration in the AAS score (baseline vs 24 months = 28 vs 25, P = 0.60).
      There was deterioration of the physical functioning dimension of the SF-36
      (baseline vs 24 months = 40 vs 32, P < 0.01), but the mental functioning
      dimension was improved (45 vs 51; P = 0.01). Watchful waiting was a safe option
      for patients in this study with ventral hernias. 

PMID- 24666866
TI  - The effect of trauma care on the temporal distribution of homicide mortality in
      Jefferson County, Alabama.
AB  - The distribution of time from acute traumatic injury to death has three peaks:
      immediate (less than or equal to one hour), early (6 to 24 hours), and late (days
      to weeks). It has been suggested that coordinated trauma care dampens the late
      peak; however, this research may be more reflective of unintentional than
      intentional deaths. This study examines whether a coordinated trauma system (TS)
      alters the temporal distribution for assault-related deaths. Data were obtained
      from homicides examined by the Jefferson County Coroner's/Medical Examiner's
      Office from 1987 to 2008. Homicides were categorized-based on year of death-as
      occurring in the presence of no TS, during TS implementation, in the early years
      of the TS, or in a mature TS. The temporal distribution of homicide mortality was
      compared among TS categories using a chi(2) test. A Cox Markov multistate model
      was used to estimate proportional changes in the temporal distribution of death
      adjusted for assault mechanism. With a TS, after adjusting for assault mechanism,
      a lower proportion of homicide victims survived through the first hour (hazard
      ratio [HR], 0.75; 95% confidence interval [CI], 0.54 to 1.03) and from one to six
      hours (HR, 0.68; 95% CI, 0.49 to 0.96). Additionally, the presence of a TS was
      associated with a proportional decrease in deaths after 24 hours (P = 0.0005).
      These results suggest that a trauma system is effective in preventing late
      homicide deaths; however, other means of preventing death (such as violence
      prevention programs) are needed to decrease the burden of immediate homicide
      related deaths. 

PMID- 24666867
TI  - A comparative analysis between laparoscopic and open adhesiolysis at a tertiary
      care center.
AB  - Laparotomy has been the favored approach regarding surgical management of small
      bowel obstruction (SBO); however, laparoscopy may offer improved outcomes.
      Patients undergoing laparoscopic lysis of adhesions (LOA) at our institution for
      SBO will have lower postoperative morbidity and 30-day mortality. Patients
      undergoing LOA at our institution, from 2000 to 2011, were reviewed. Categorical
      data were analyzed with chi(2) or Fisher's exact tests. Continuous data were
      analyzed with Student's t test or Wilcoxon rank sum. One hundred two (38
      laparoscopic, 64 open) LOA cases were selected. Perioperative contamination and
      conservative management were higher in the open group. Open cases had a greater
      incidence of intensive care unit (ICU) admissions and longer length of stay.
      Stratified analysis determined a strong association between perioperative
      contamination and a higher incidence of ICU admission, perioperative
      contamination and longer LOS, and conservative management and longer LOS.
      Finally, patient outcome did not differ between those treated by surgeons trained
      in minimally invasive surgery (MIS) compared with those not trained in MIS.
      Careful consideration of surgical approach and timing is called for in all
      patients with SBO; however, whenever possible, laparoscopic preference should be
      given to most patients in an expeditious fashion irrespective of MIS training. 

PMID- 24666868
TI  - The risk of lymph node involvement in malignant cutaneous adnexal tumors.
AB  - Malignant cutaneous adnexal tumors (MCATs) are rare neoplasms that do not have a
      well-studied treatment algorithm. They are generally treated by excision alone.
      Given its successful application in other cutaneous malignancies, sentinel lymph
      node biopsy (SLNB) has been advocated by some for use in MCATs. A retrospective
      chart review was performed. Clinicopathological factors, recurrence patterns, and
      long-term follow-up were documented. Survival analysis was performed. Forty-eight
      subjects were identified. Mean age was 69 years with locations on the face (52%),
      including periocular sites (16%), extremities (25%), and all other sites (7%).
      Histologic distribution was sebaceous carcinoma (56%), porocarcinoma (17%),
      eccrine carcinoma (13%), adenocarcinoma (10%), and hidradenocarcinoma (4%). Mean
      follow-up was 3.9 years (range, 0 to 17 years). Nine subjects (18.8%) recurred
      locally, and recurrence was inversely associated with age (P = 0.04). Four (8.3%)
      demonstrated lymph node involvement, none without first developing local
      recurrence. Five-year disease-specific survival was 97 per cent (confidence
      interval, 81.4 to 99.6%). Despite being one of the largest reported analyses of
      MCATs, this study is limited by the small number of subjects. MCATs seemingly
      develop nodal recurrence only after demonstrating aggressive local biology. SLNB
      may best be applied selectively, possibly only in patients with local recurrence.

PMID- 24666869
TI  - Ligaments of the rectum: anatomical and surgical considerations.
AB  - The ligaments of the rectum have been the subject of controversy for decades. Not
      only have their contents and components been a source of contention, but also the
      very existence of these ligaments has been called into question. This article
      explores the anatomical features of these ligaments with implications for
      surgical treatment of rectal prolapse, rectal cancer, and resection of the rectum
      and mesorectum. A theory about the evolution of the lateral rectal ligaments and
      the mesorectum in humans and higher mammals is also presented. 

PMID- 24666870
TI  - Predictors of hospital discharge to an extended care facility after major general
      thoracic surgery.
AB  - Failure to anticipate the need to discharge patients to rehabilitation centers
      and skilled nursing facilities results in expensive delays in the discharge of
      patients after surgery. Early identification of patients at high risk for
      discharge to these extended care facilities could mitigate these delays and
      expenditures. The purpose of this study was to identify preoperative patient
      factors associated with discharge to extended care facilities after major general
      thoracic surgery. Discharge records were identified for all patients undergoing
      major general thoracic surgery admitted to a university hospital between January
      2006 and May 2009 who had a stay of longer than one day. The following risk
      factors were selected a priori based on clinical judgment: age, preoperative
      albumin, preoperative Zubrod score, history of peripheral vascular disease, and
      use of home oxygen. Multiple logistic regression analysis was used to estimate
      the statistical significance and magnitude of risk associated with each predictor
      of patient discharge to extended care facilities. Of the 1646 patients
      identified, 68 (4.1%) were discharged to extended care facilities. Hospital
      length of stay was on average six days longer for patients discharged to these
      facilities than for patients discharged home (P < 0.0001). Multivariate analysis
      demonstrated that advanced age, lower preoperative albumin, and increased
      preoperative Zubrod score were statistically significant predictors of discharge
      to extended care facilities. Age, preoperative nutritional status, and functional
      status are strong predictors of patient discharge to extended care facilities.
      Early identification of these patients may improve patient discharge planning and
      reduce hospital length of stay after major thoracic surgery. 

PMID- 24666871
TI  - Hypometabolizers: characteristics of obese patients with abnormally low resting
      energy expenditure.
AB  - Weight gain or loss is determined by the difference between calorie intake and
      energy expenditure. The Mifflin metabolic equation most accurately predicts
      resting energy expenditure (REE) in morbidly obese patients. Hypometabolizers
      have a measured REE that is much less than predicted and pose the greatest
      challenge for weight loss induced by restriction of calorie intake. We studied
      628 morbidly obese patients (467 female and 161 men, aged 52.5 +/- 15.7 years,
      body mass index [BMI] of 42.6 +/- 7.6 m/kg(2) [mean +/- SD]). REE was measured
      using the MedGem(r) device (REEm) and the percentage variance (DeltaREE%) from
      the Mifflin-predicted expenditure (REEp) was calculated. Patients with DeltaREE%
      more than 1 standard deviation from the mean were defined as hypometabolizers
      (REEm greater than 27% below REEp) and hypermetabolizers (REEm less than 13%
      above REEp), respectively. Hypometabolizers had greater REEp (1900 +/- 301 vs
      1719 +/- 346 calories, P = 0.005) and lower REEm (1244 +/- 278 vs 2161 +/- 438
      calories, P < 0.0001) than hypermetabolizers. Hypometabolizers, when compared
      with hypermetabolizers, were taller (167.2 +/- 8.4 vs 164.0 +/- 10.9 cm, P =
      0.04), heavier (123.6 +/- 22.2 vs 110.2 +/- 23.1 kg, P = 0.006), and had
      increased BMI (44.1 +/- 6.5 vs 40.8 +/- 6.5 kg/m(2), P = 0.04). Other measured
      anthropometrics were not different between hypo- and hypermetabolizers.
      Hypometabolizers were less likely to be diabetic (23 vs 43%, P = 0.03) and more
      likely to be black (25 vs 5%, P = 0.002) than hypermetabolizers. This study
      defines hypometabolizers as having variance in REEm more than 27 per cent below
      that predicted by the Mifflin equation. We could not identify any distinguishing
      phenotypic characteristics of hypometabolizers, suggesting an influence unrelated
      to body composition. 

PMID- 24666872
TI  - Comparison of standard distal pancreatectomy and splenectomy with radical
      antegrade modular pancreatosplenectomy.
AB  - Radical antegrade modular pancreatosplenectomy (RAMPS) has been reported to
      provide improved margin resection and lymph node retrieval for tumors of the body
      and tail of the pancreas compared with standard resection. We examined our
      experience with RAMPS and standard resection to determine differences in
      clinicopathologic outcomes. A comparison of RAMPS procedures was made to standard
      distal pancreatectomy and splenectomy examining various clinicopathologic
      variables through retrospective chart review. Twenty-six patients underwent
      distal pancreatectomy with or without splenectomy between November 2004 and June
      2011. Twenty patients underwent standard resection and six patients underwent
      RAMPS procedures for a variety of histologies. As a result of the heterogeneity
      of diseases, which included benign lesions, margin status was not applicable in
      some cases and therefore was not assessed overall. Fisher's exact test and
      Wilcoxon rank sum tests demonstrated a significant difference in number of lymph
      nodes removed with mean of 4.3 and 11.2 lymph nodes obtained for standard
      resection and RAMPS, respectively (P = 0.03). The RAMPS procedure for lesions of
      the body and tail of the pancreas retrieved significantly more lymph nodes than
      standard distal pancreatectomy and splenectomy. It should be the preferred
      surgical approach when lymph node count is important for tumor staging. 

PMID- 24666873
TI  - Time to resuscitate a sacred cow...with normal saline.
AB  - Normal saline (NS) is not used for trauma resuscitation because of its potential
      for acidosis. Lactated Ringer's (LR) is preferred instead. However, the two
      crystalloids have never been compared in trauma patients. We hypothesized that NS
      would be an acceptable fluid for resuscitation in the trauma patient. In 2011, a
      Level I trauma center switched resuscitation fluid from LR to NS. Admissions
      before and after the change were retrospectively reviewed. Demographics, vitals,
      blood work, and fluid intake were recorded over 24 hours. Acidosis level,
      stratified by Injury Severity Score (ISS), was compared. Four hundred ten
      patients were included, 207 in the LR cohort and 203 in the NS. Chloride (LR
      105.26 +/- 4.75 vs NS 106.48 +/- 4.19), base excess (-2.53 +/- 3.77 vs -3.28 +/-
      4.15), pH (7.37 +/- 0.08 vs 7.36 +/- 0.07), and bicarbonate (22.83 +/- 3.45 vs
      21.65 +/- 5.06) were statistically different but not clinically significant. This
      was also true when results were stratified by ISS. In addition, there was no
      difference in the number of blood gases drawn between the groups (584 vs 544, P =
      nonsignificant). NS resuscitation is a safe, viable alternative to LR in the
      trauma population studied. Its use carries a potentially substantial cost savings
      on a national level. 

PMID- 24666874
TI  - Addressing trainees' concerns through a resident advocacy committee.

PMID- 24666875
TI  - Is surgery always necessary in patients with abdominal pain and computed
      tomography-suggested intussusception?

PMID- 24666876
TI  - Prospective evaluation of posttraumatic vasospasm: determining its clinical
      significance after traumatic brain injury.

PMID- 24666877
TI  - Retrograde flow upper extremity fillet flap for coverage of a large thoracic wall
      defect.

PMID- 24666878
TI  - Treatment of perforated appendicitis in children: focus on phlegmon.

PMID- 24666879
TI  - The non-designated preliminary pathway in general surgery residency: implications
      for the national surgical workforce.

PMID- 24666880
TI  - Neuroendocrine tumor of the gallbladder treated with neoadjuvant chemotherapy and
      surgery.

PMID- 24666881
TI  - Cardiac rhabdomyoma presenting as infective endocarditis: a case report.
AB  - We report a case of cardiac rhabdomyomas in an infant who presented with right
      ventricular tachycardia, and a clinical picture of infective endocarditis.
      Typical features of tuberous sclerosis developed subsequently. To the best of our
      knowledge, cardiac rhabdomyoma has not been reported previously in association
      with infective endocarditis. 

PMID- 24666882
TI  - Sexual concerns of cardiac patients: A psychometric analysis.
AB  - The primary aim of this study was to evaluate the psychometric properties of the
      Steinke Sexual Concerns Inventory-General Cardiac Version (SSCI-GCV) and to
      examine its use across multiple cardiac diagnoses. A sub-analysis of a cross
      sectional sample of 205 cardiac patients from the central USA was completed. Our
      analyses yielded promising evidence that the SSCI-GCV is a reliable (Cronbach's
      alpha = 0.86) and valid measure of sexual concerns and supported three subscales
      for this 11-item instrument. Further means testing suggested that participants
      with a diagnosis of stroke or kidney disease reported more sexual concerns than
      those without such diagnoses, but differences were not found for any specific
      cardiac health problem or intervention. These findings support the use of the
      SSCI-GCV as a brief and easily administered instrument that can be used to
      broadly assess sexual concerns in cardiac populations and to inform sexual
      counselling of cardiac patients in practice.

PMID- 24666883
TI  - Qualitative and quantitative assessment of viral contamination in bivalve
      molluscs harvested in Italy.
AB  - Bivalve molluscs are a well documented source of viral infection. Further data on
      shellfish viral contamination are needed to implement European Regulations with
      sanitary measures more effective against viral pathogens. To this aim, 336
      samples of bivalve molluscs (185 mussels, 66 clams, 23 oysters and 62 samples
      from other species) collected in harvesting areas of class A and B of four
      Italian Regions were analyzed for qualitative and quantitative determination of
      hepatitis A virus (HAV) and Norovirus (NoV) GI and GII, using real time RT-PCR.
      The results showed a wide diffusion of viral contamination in the shellfish
      production areas considered. HAV prevalence was low (0.9%) with contamination
      levels that varied from 5 to 7 * 10(2)copies/g. On the contrary, NoV showed a
      high prevalence (51.5%), with a large variability according to the group
      considered (e.g. 47.8% for Crassostrea in Veneto, 79.7% for Mytilus in Campania,
      84.6% for Tapes in Sardinia). NoV contamination affected class A and class B
      production areas to a different extent, with a statistically significant
      difference in both contamination prevalence (22.1% vs. 66.3%; p<0.0001) and
      quantity (average contamination level of 3.1 * 10(2) vs. 1.9 * 10(3) copies/g;
      p<0.05). The different species analyzed from class B harvesting areas (Mytilus,
      Tapes/Ruditapes and Crassostrea) showed a NoV prevalence respectively of 70.3%,
      66.0% and 47.8% but comparable NoV contamination levels (between 8.4 * 10(2) and
      4.9 * 10(3)copies/g). Other two bivalve species considered in the study (Donax
      spp. and Solen spp.) showed a relevant NoV presence (40.0% and 34.4% of samples).
      Finally, samples analyzed before and after commercial purification treatment
      showed a decrease of contamination prevalence after the treatment, but
      inconsistent results were recorded on NoV levels. The data obtained, together
      with other quantitative information to estimate consumer exposure, in association
      with studies on dose-response and on the effectiveness of post-harvest
      treatments, will provide a useful tool for the definition of microbiological
      criteria related to the different shellfish species.

PMID- 24666884
TI  - Clinical safety, tolerability and efficacy of combination tolterodine/pilocarpine
      in patients with overactive bladder.
AB  - AIMS: The purpose of this study was to assess the safety, tolerability and impact
      on overactive bladder (OAB) symptoms of a novel combination of tolterodine
      immediate-release (IR) 2 mg and delayed-release pilocarpine 9 mg in patients with
      OAB. METHODS: Eligible patients with OAB were randomised to each of three
      treatments [tolterodine/pilocarpine (2/9 mg), tolterodine IR 2 mg or placebo]
      twice daily for 4 weeks in a double-blind, crossover fashion. At the end of the
      12-week, double-blind treatment period, patients could enter an open-label
      extension during which they were re-randomised to either tolterodine/pilocarpine
      (3/13.5 mg) twice daily or tolterodine extended-release 4 mg once daily for 12
      weeks. RESULTS: A total of 138 patients were randomised to double-blind
      medication. Both tolterodine/pilocarpine (2/9) and tolterodine IR 2 mg
      significantly reduced incontinence episodes and daily micturitions (p < 0.001 vs.
      placebo), with similar reductions in symptoms observed between active treatment
      groups. Tolterodine/pilocarpine (2/9) was associated with consistently lower
      Visual Analogue Scale (VAS) scores for all dry mouth parameters compared with
      tolterodine alone. Salivary flow over a 3 h period remained fairly constant after
      tolterodine/pilocarpine (2/9) administration, similar to placebo, but decreased
      markedly after administration of tolterodine alone. In the extension study,
      patients receiving tolterodine/pilocarpine (3/13.5) reported comparable dry mouth
      VAS scores to tolterodine extended-release alone without additional side effects
      or loss of efficacy. The combination was well tolerated, and the adverse effects
      observed were consistent with the known safety profiles of tolterodine and
      pilocarpine. CONCLUSIONS: A combination of tolterodine/pilocarpine (2/9)
      effectively reduced the incidence of dry mouth compared with tolterodine IR alone
      while maintaining treatment efficacy in OAB.

PMID- 24666885
TI  - Automated DNA-based plant identification for large-scale biodiversity assessment.
AB  - Rapid degradation of tropical forests urges to improve our efficiency in large
      scale biodiversity assessment. DNA barcoding can assist greatly in this task, but
      commonly used phenetic approaches for DNA-based identifications rely on the
      existence of comprehensive reference databases, which are infeasible for
      hyperdiverse tropical ecosystems. Alternatively, phylogenetic methods are more
      robust to sparse taxon sampling but time-consuming, while multiple alignment of
      species-diagnostic, typically length-variable, markers can be problematic across
      divergent taxa. We advocate the combination of phylogenetic and phenetic methods
      for taxonomic assignment of DNA-barcode sequences against incomplete reference
      databases such as GenBank, and we developed a pipeline to implement this approach
      on large-scale plant diversity projects. The pipeline workflow includes several
      steps: database construction and curation, query sequence clustering, sequence
      retrieval, distance calculation, multiple alignment and phylogenetic inference.
      We describe the strategies used to establish these steps and the optimization of
      parameters to fit the selected psbA-trnH marker. We tested the pipeline using
      infertile plant samples and herbivore diet sequences from the highly threatened
      Nicaraguan seasonally dry forest and exploiting a valuable purpose-built
      resource: a partial local reference database of plant psbA-trnH. The selected
      methodology proved efficient and reliable for high-throughput taxonomic
      assignment, and our results corroborate the advantage of applying 'strict' tree
      based criteria to avoid false positives. The pipeline tools are distributed as
      the scripts suite 'BAGpipe' (pipeline for Biodiversity Assessment using GenBank
      data), which can be readily adjusted to the purposes of other projects and
      applied to sequence-based identification for any marker or taxon.

PMID- 24666886
TI  - Over-expression of Arabidopsis AtCHR23 chromatin remodeling ATPase results in
      increased variability of growth and gene expression.
AB  - BACKGROUND: Plants are sessile organisms that deal with their -sometimes adverse-
      environment in well-regulated ways. Chromatin remodeling involving SWI/SNF2-type
      ATPases is thought to be an important epigenetic mechanism for the regulation of
      gene expression in different developmental programs and for integrating these
      programs with the response to environmental signals. In this study, we report on
      the role of chromatin remodeling in Arabidopsis with respect to the variability
      of growth and gene expression in relationship to environmental conditions.
      RESULTS: Already modest (2-fold) over-expression of the AtCHR23 ATPase gene in
      Arabidopsis results in overall reduced growth compared to the wild-type. Detailed
      analyses show that in the root, the reduction of growth is due to reduced cell
      elongation. The reduced-growth phenotype requires sufficient light and is
      magnified by applying deliberate abiotic (salt, osmotic) stress. In contrast, the
      knockout mutation of AtCHR23 does not lead to such visible phenotypic effects. In
      addition, we show that over-expression of AtCHR23 increases the variability of
      growth in populations of genetically identical plants. These data indicate that
      accurate and controlled expression of AtCHR23 contributes to the stability or
      robustness of growth. Detailed RNAseq analyses demonstrate that upon AtCHR23 over
      expression also the variation of gene expression is increased in a subset of
      genes that associate with environmental stress. The larger variation of gene
      expression is confirmed in individual plants with the help of independent qRT-PCR
      analysis. CONCLUSIONS: Over-expression of AtCHR23 gives Arabidopsis a phenotype
      that is markedly different from the growth arrest phenotype observed upon over
      expression of AtCHR12, the paralog of AtCHR23, in response to abiotic stress.
      This demonstrates functional sub-specialization of highly similar ATPases in
      Arabidopsis. Over-expression of AtCHR23 increases the variability of growth among
      genetically identical individuals in a way that is consistent with increased
      variability of expression of a distinct subset of genes that associate with
      environmental stress. We propose that ATCHR23-mediated chromatin remodeling is a
      potential component of a buffer system in plants that protects against
      environmentally-induced phenotypic and transcriptional variation.

PMID- 24666887
TI  - Factors influencing adherence to regular exercise in middle-aged women: a
      qualitative study to inform clinical practice.
AB  - BACKGROUND: About half of women decrease their regular exercise during middle
      age. Concurrently, they experience a reduction in basal metabolic rate and loss
      of lean muscle as they transition to menopause. The combined effects place these
      women at increased risk for body weight gain and associated co-morbidities.
      Further research is required to better assess their barriers to regular exercise
      and to develop more applied knowledge aimed to improve the applicability of
      clinical interventions aimed at this population. The main aim of this study was
      to identify enablers and barriers influencing adherence to regular exercise in
      middle-aged women who exercise. METHODS: An interpretive description qualitative
      study was conducted using individual interviews. The two key questions were
      focused on planning to engage in physical activity and succeeding or planning to
      engage in physical activity and not succeeding. Inductive content analysis was
      used. RESULTS: Fifty-three women interviewed were aged 40-62 years and
      experiencing mild to moderate menopausal symptoms. Six broad themes influencing
      adhering to regular exercise were: routine, intrinsic motivation, biophysical
      issues, psychosocial commitments, environmental factors, and resources. Common
      sub-themes were identified as enabling factors: daily structure that incorporated
      physical activity (broad theme routine), anticipated positive feelings associated
      with physical activity (intrinsic), and accountability to others (psychosocial).
      Other common sub-themes identified as barriers were disruptions in daily
      structure (routine), competing demands (routine) and self-sacrifice
      (psychosocial). CONCLUSIONS: The most common barrier middle-aged women describe
      as interfering with adhering to regular exercise was attributable to the demands
      of this life stage at home and with others. Lack of time and menopausal symptoms
      were not identified as the common barriers. To support women to adhere to regular
      exercise, healthcare professionals should consider a narrative approach to
      assessing barriers and focus on enablers to overcoming identified barriers.

PMID- 24666888
TI  - Systematic changes in position sense accompany normal aging across adulthood.
AB  - BACKGROUND: Development of clinical neurological assessments aimed at separating
      normal from abnormal capabilities requires a comprehensive understanding of how
      basic neurological functions change (or do not change) with increasing age across
      adulthood. In the case of proprioception, the research literature has failed to
      conclusively determine whether or not position sense in the upper limb
      deteriorates in elderly individuals. The present study was conducted a) to
      quantify whether upper limb position sense deteriorates with increasing age, and
      b) to generate a set of normative data that can be used for future comparisons
      with clinical populations. METHODS: We examined position sense in 209 healthy
      males and females between the ages of 18 and 90 using a robotic arm position
      matching task that is both objective and reliable. In this task, the robot moved
      an arm to one of nine positions and subjects attempted to mirror-match that
      position with the opposite limb. Measures of position sense were recorded by the
      robotic apparatus in hand-and joint-based coordinates, and linear regressions
      were used to quantify age-related changes and percentile boundaries of normal
      behaviour. For clinical comparisons, we also examined influences of sex (male
      versus female) and test-hand (dominant versus non-dominant) on all measures of
      position sense. RESULTS: Analyses of hand-based parameters identified several
      measures of position sense (Variability, Shift, Spatial Contraction, Absolute
      Error) with significant effects of age, sex, and test-hand. Joint-based
      parameters at the shoulder (Absolute Error) and elbow (Variability, Shift,
      Absolute Error) also exhibited significant effects of age and test-hand.
      CONCLUSIONS: The present study provides strong evidence that several measures of
      upper extremity position sense exhibit declines with age. Furthermore, this data
      provides a basis for quantifying when changes in position sense are related to
      normal aging or alternatively, pathology.

PMID- 24666890
TI  - A review of the surface and internal anatomy of the caudal canal in children.
AB  - The anatomy of the sacral hiatus and caudal canal is prone to significant
      variation, yet studies assessing this in the pediatric population remain limited.
      Awareness of the possible anatomical variations is critical to the safety and
      success of caudal epidural blocks, particularly when image guidance is not
      employed. This systematic review analyzes the available evidence on the clinical
      anatomy of the caudal canal in pediatric patients, emphasizing surface anatomy
      and internal anatomical variations. A literature search using three electronic
      databases and standard pediatric and anatomy reference texts was conducted
      yielding 24 primary and seven secondary English-language sources. Appreciating
      that our current landmark-guided approaches to the caudal canal are not well
      studied in the pediatric population is important for both clinicians and
      researchers. 

PMID- 24666889
TI  - The consequences of sudden fluid shifts on body composition in critically ill
      patients.
AB  - INTRODUCTION: Estimation of body composition as fat-free mass (FFM) is subjected
      to many variations caused by injury and stress conditions in the intensive care
      unit (ICU). Body cell mass (BCM), the metabolically active part of FFM, is
      reported to be more specifically correlated to changes in nutritional status.
      Bedside estimation of BCM could help to provide more valuable markers of
      nutritional status and may promote understanding of metabolic consequences of
      energy deficit in the ICU patients. We aimed to quantify BCM, water compartments
      and FFM by methods usable at the bedside for evaluating the impact of sudden and
      massive fluid shifts on body composition in ICU patients. METHODS: We conducted a
      prospective experimental study over an 6 month-period in a 18-bed ICU. Body
      composition of 31 consecutive hemodynamically stable patients requiring acute
      renal replacement therapy for fluid overload (ultrafiltration >=5% body weight)
      was investigated before and after the hemodialysis session. Intra-(ICW) and
      extracellular (ECW) water volumes were calculated from the raw values of the low-
      and high-frequency resistances measured by multi-frequency bioelectrical
      impedance. BCM was assessed by a calculated method recently developed for ICU
      patients. FFM was derived from BCM and ECW. RESULTS: Intradialytic weight loss
      was 3.8 +/- 0.8 kg. Percentage changes of ECW (-7.99 +/- 4.60%) and of ICW (-7.63
      +/- 5.11%) were similar, resulting ECW/ICW ratio constant (1.26 +/- 0.20). The
      fall of FFM (-2.24 +/- 1.56 kg, -4.43 +/- 2.65%) was less pronounced than the
      decrease of ECW (P < 0.001) or ICW (P < 0.001). Intradialytic variation of BCM
      was clinically negligible (-0.38 +/- 0.93 kg, -1.56 +/- 3.94%) and was
      significantly less than FFM (P < 0.001). CONCLUSIONS: BCM estimation is less
      driven by sudden massive fluid shifts than FMM. Assessment of BCM should be
      preferred to FFM when severe hydration disturbances are present in ICU patients.

PMID- 24666891
TI  - Quercetin ameliorates tunicamycin-induced endoplasmic reticulum stress in
      endothelial cells.
AB  - OBJECTIVE: Endothelial dysfunction highlights that it is a potential contributor
      in the pathogenesis of vascular complications arising from endoplasmic reticulum
      stress (ER stress) and has been emerging as a main causative factor in vascular
      failure. Here, we hypothesize that the natural flavonoid, quercetin plays an
      effective role in reducing ER stress in human umbilical vein endothelial cells.
      MATERIALS AND METHODS: Human umbilical vein endothelial cells were pre-treated
      with different concentrations of quercetin (0-100 MUm) before inducing ER stress
      using tunicamycin (TUN) (0.75 MUg/ml); cytotoxicity was assessed by MTT assay.
      Expression levels of ER stress responsive genes, antioxidant enzymes and
      apoptotic markers were assessed by qRT-PCR, while roles of caspase-3 and PARP
      cleavage were measured by western blot analysis. RESULTS: Quercetin pre-treatment
      at 25 and 50 MUm had a cytoprotective effect on cells against TUN-induced
      toxicity. Quercetin administration modulated expression level of ER stress genes
      coding for glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein
      (CHOP), and antioxidant enzymes such as superoxide dismutase and catalase, along
      with free radical generation assessed by malondialdehyde assay. Induction of
      apoptosis was prevented with reduction in expression level of Bax, and
      concomitant increase in Bcl-2 levels, thus proving its potential against ER
      stress. CONCLUSION: The current study indicates that quercetin modulated stress
      responsive genes GRP78 and CHOP, helping endothelial cells prevent TUN-induced ER
      stress.

PMID- 24666892
TI  - Parasitic antigens alter macrophage polarization during Schistosoma japonicum
      infection in mice.
AB  - BACKGROUND: Schistosome eggs are trapped in host liver and elicit severe hepatic
      granulomatous inflammation, which can lead to periportal fibrosis, portal
      hypertension, hemorrhage, or even death in the host. It was reported that the
      macrophage plays an important role in host immune responses to schistosome
      infection. Nitric oxide (NO) produced by classically activated macrophages (M1
      macrophages) is cytotoxic to schistosomula and can prevent hepatic schistosomal
      fibrosis, while arginase-1 (Arg-1) expressed by alternatively activated
      macrophages (M2 macrophages) promotes hepatic schistosomal fibrosis. However, the
      dynamics of macrophage polarization, as well as the possible factors that
      regulate macrophage polarization, during schistosome infection remain unclear.
      METHODS: We first analyzed M1 and M2-phenotypic markers of peritoneal macrophages
      from mice infected with Schistosoma japonicum (S. japonicum) at indicated time
      points using flow cytometry (FCM) analysis and real-time PCR. Then we treated
      peritoneal macrophages from normal mice with schistosome worm antigen (SWA) or
      schistosome soluble egg antigen (SEA) and determined M1 and M2-phenotypic
      markers, in order to identify macrophage polarization in responding to
      schistosomal antigens. RESULTS: In this study, we showed that macrophages were
      preferentially differentiated into the M1 subtype during the acute stage of S.
      japonicum infection. However, the level of M1 macrophages decreased and M2
      macrophages significantly increased during the chronic stage of infection.
      Furthermore, we showed that SWA favors the generation of M1 macrophages, whereas
      SEA preferentially promotes M2-polarized phenotype. CONCLUSION: These findings
      not only reveal the parasite antigen-driven dynamic changes in macrophage
      polarization, but also suggest that manipulation of macrophage polarization may
      be of therapeutic benefit in controlling excessive hepatic granulomas and
      fibrosis in the host with schistosomiasis.

PMID- 24666894
TI  - Determination of the location of the mental foramen: a critical review.
AB  - INTRODUCTION: The mental foramen (MF) is an important landmark to consider during
      surgical endodontic procedures. The purpose of this review article was to discuss
      the variety of techniques that have been developed to determine the location of
      the MF, to make recommendations for the current best technique available, and to
      discuss upcoming technologies. METHODS: Articles that have addressed the location
      of the MF were evaluated for information pertinent to include in this review.
      RESULTS: Different technologies have been used to help operators determine the
      clinical location of the MF. Most of the techniques have shortcomings such as
      magnification, radiation, and cost. Cone-beam computed tomographic imaging is the
      best current available imaging technology to determine the accurate location of
      the MF, but it has shortcomings such as radiation, cost, and not being real time,
      which means the data must be interpreted at a later time than when the
      information was computed. CONCLUSIONS: In the future, magnetic resonance imaging
      and ultrasound technologies seem to provide promising noninvasive imaging
      techniques.

PMID- 24666893
TI  - Clinical effectiveness of basic root canal treatment after 24 months: a
      randomized controlled trial.
AB  - INTRODUCTION: The purpose of this study was to investigate the effectiveness of
      basic root canal treatment (BRT) with tactile working length determination in
      terms of radiographic and clinical outcome parameters compared with endodontic
      treatment with standard radiographic working length control. METHODS: This was a
      clinical, multicenter, controlled, open-label trial to evaluate BRT effectiveness
      after 24 months. The primary end point was the apical extension score of the
      radiographic quality parameter of root canal fillings. The secondary radiographic
      end point was the periapical index, and the secondary clinical end point was
      tooth tender to percussion. The safety end point was tooth loss as a consequence
      of endodontic failure. Statistical analyses of binary and categoric data were
      calculated using cross tables and the chi-square test. RESULTS: BRT with tactile
      working length determination compared with standard radiographic working length
      control did not significantly differ in terms of radiographic and clinical
      outcomes after 24 months. The apical extension of the root canal fillings and the
      periapical anatomic structures showed no significant differences according to
      radiographic analyses (P = .5). Corresponding results were found in clinical
      aspects of tooth tender to percussion (P = .6) and tooth loss (P = .7).
      CONCLUSIONS: Tactile working length determination in BRT resulted in comparable
      treatment outcomes compared with standard endodontic treatment with radiographic
      working length control and turned out to be an accurate method in BRT.

PMID- 24666895
TI  - Prevalence of ciliated epithelium in apical periodontitis lesions.
AB  - INTRODUCTION: This article reports on the morphologic features and the frequency
      of ciliated epithelium in apical cysts and discusses its origin. METHODS: The
      study material consisted of 167 human apical periodontitis lesions obtained
      consecutively from patients presenting for treatment during a period of 12 years
      in a dental practice operated by one of the authors. All of the lesions were
      obtained still attached to the root apices of teeth with untreated (93 lesions)
      or treated canals (74 lesions). The former were obtained by extraction and the
      latter by extraction or apical surgery. Specimens were processed for
      histopathologic and histobacteriologic analyses. Lesions were classified, and the
      type of epithelium, if present, was recorded. RESULTS: Of the lesions analyzed,
      49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated
      teeth, and 23 (47%) related to root canal-treated teeth. Ciliated columnar
      epithelium was observed partially or completely lining the cyst wall in 4 cysts,
      and all of them occurred in untreated maxillary molars. Three of these lesions
      were categorized as pocket cysts, and the other was a true cyst. CONCLUSIONS:
      Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the
      apical periodontitis lesions and 8% of the cysts of endodontic origin in the
      population studied. This epithelium is highly likely to have a sinus origin in
      the majority of cases. However, the possibility of prosoplasia or upgraded
      differentiation into ciliated epithelium from the typical cystic lining squamous
      epithelium may also be considered.

PMID- 24666896
TI  - Signaling pathways activation by primary endodontic infectious contents and
      production of inflammatory mediators.
AB  - INTRODUCTION: This study investigated the bacterial community involved in primary
      endodontic diseases, evaluated its ability to activate the macrophage Toll-like
      receptor 4 receptor through p38 mitogen-activated protein kinase (MAPK) and
      nuclear factor kappa B (NF-kappaB) signaling pathways, and determined the levels
      of endotoxins and interleukins (interleukin [IL]-6 and -10) produced by
      endodontic content-stimulated macrophages. METHODS: Samples were taken from 21
      root canals by using sterile/apyrogenic paper points. Raw 264.7 macrophages were
      stimulated with root canal contents. Checkerboard DNA-DNA hybridization was used
      for bacterial analysis and the limulus amebocyte lysate assay for endotoxin
      measurement; p38 MAPK and NF-kappaB activation was determined by Western blot
      analysis. IL-6 and IL-10 were measured using the enzyme-linked immunosorbent
      assay. RESULTS: Bacteria and endotoxins were detected in 100% of the samples
      (21/21). The most frequently observed species were Parvimonas micra (16/21, 76%),
      Fusobacterium nucleatum ssp. nucleatum (15/21, 71%), and Porphyromonas
      endodontalis (14/21, 66%). Correlations were found between endotoxins and IL-6
      and IL-10 (P < .05); p38 phosphorylation had a peak at 60 minutes, and NF-kappaB
      was quickly activated after 10 minutes of stimulation. CONCLUSIONS: It was
      concluded that the complex bacterial community was shown to be a potent activator
      of TLR-4 determined by the p38 MAPK and NF-kappaB signaling pathways, culminating
      in a high antigenicity against macrophages through the levels of IL-6 and IL-10,
      all significantly affected by endotoxin levels.

PMID- 24666897
TI  - Comparison of clinical outcomes of endodontic microsurgery: 1 year versus long
      term follow-up.
AB  - INTRODUCTION: The purpose of this study was to examine and compare the clinical
      outcome of endodontic microsurgery after 1 year of follow-up and over a period of
      4 years. METHODS: The database of the Department of Conservative Dentistry,
      Yonsei University, Seoul, South Korea, was searched for patients who had
      undergone endodontic microsurgery and had been evaluated 1 year after surgery and
      over a period of 4 years. Two examiners independently evaluated the postoperative
      radiographs taken 1 year after surgery and over a period of 4 years using Rud's
      criteria. To analyze and compare the success rate based on the observation
      period, the McNemar test was performed with a significance level of 0.05.
      RESULTS: The study included 115 cases. Using Rud's criteria, the overall success
      rate of cases with 4 or more years of follow-up was 87.8% compared with 91.3% at
      1 year of follow-up. There was no significant difference between the follow-up
      periods (P = .344). CONCLUSIONS: There was no significant difference in the
      clinical outcome after endodontic microsurgery when comparing 1-year follow-up
      periods with longer follow-up periods.

PMID- 24666898
TI  - Role of ultrasonography in differentiating facial swellings of odontogenic
      origin.
AB  - INTRODUCTION: Differentiating an acute, odontogenic facial swelling clinically as
      cellulitis or an abscess has not been thoroughly investigated in endodontics. It
      has been suggested in the medical and dental literature that the use of
      ultrasound may aid in differentiating cellulitis from an abscess. Therefore, if
      ultrasound were more accurate than a blind incision for drainage procedure in
      locating purulence, perhaps the outcome of the incision for drainage procedure
      would be beneficial in the resolution of odontogenic infections. The purpose of
      this prospective study was to compare clinical examination plus ultrasonography
      versus clinical examination alone in differentiating cellulitis from abscesses in
      patients with facial swelling of odontogenic origin. METHODS: Eighty-two
      emergency patients participated in this study. Each patient was examined and
      diagnosed by clinical examination and clinical examination plus ultrasonography.
      An incision for drainage procedure was performed, and a definitive diagnosis was
      recorded as cellulitis (no purulence) or an abscess (presence of purulence).
      RESULTS: With the incision for drainage procedure, cellulitis occurred 37% of the
      time and abscesses 63%. With clinical examination alone, a correct diagnosis was
      made 68% of the time. With clinical examination plus ultrasonography, a correct
      diagnosis was made 70% of the time. There was no statistically significant
      difference between the 2 examination methods. CONCLUSIONS: The addition of
      ultrasonography to a clinical examination did not significantly increase the
      number of correct diagnoses.

PMID- 24666899
TI  - Cellular and molecular tissue response to triple antibiotic intracanal dressing.
AB  - INTRODUCTION: The aim of this study was to characterize the response of mouse
      subcutaneous tissue to triple antibiotic paste (TAP) using conventional light
      microscopy and real-time PCR (qRT-PCR). METHODS: Polyethylene tubes containing
      TAP or calcium hydroxide (CH) (ie, the control group) were implanted in mouse
      subcutaneous tissue. Animals that received empty tubes or no tubes were used as
      additional controls. After periods of 7, 21, and 63 days postimplantation, the
      specimens were removed and subjected to histologic processing. The number of
      inflammatory cells and vessels, vessel areas, vascular density, and relative
      percentage of collagen were evaluated. Gene expression of proinflammatory
      (interleukin-1 beta, tumor necrosis factor alpha, and interleukin 17) and anti
      inflammatory (transforming growth factor beta) cytokines and angiogenic factors
      (vascular endothelial growth factor and hypoxia-inducible factor-1 alpha) was
      quantified by 7 and 21 days postimplantation. Results were analyzed using the
      Student t test, analysis of variance, and the Tukey test (alpha = 0.05). RESULTS:
      TAP induced an exuberant inflammatory and angiogenic response, with higher
      numbers of inflammatory cells, higher vascular area and density, and lower
      relative percentage of collagen compared with CH. In general, the expression of
      genes involved in inflammation and angiogenesis was higher in the TAP group
      compared with animals that received CH or empty tubes. CONCLUSIONS: The response
      of mouse subcutaneous tissue to TAP was characterized by exuberant and persistent
      inflammatory and angiogenic responses with no repair and high gene expression of
      biomarkers associated with inflammation and angiogenesis.

PMID- 24666900
TI  - Dentin extends the antibacterial effect of endodontic sealers against
      Enterococcus faecalis biofilms.
AB  - INTRODUCTION: The purpose of this study was to evaluate the antimicrobial effects
      of root canal sealers on Enterococcus faecalis biofilms in dentinal tubules by
      using a novel dentin infection model. METHODS: Cells of E. faecalis were
      introduced into the dentinal tubules by centrifugation and incubated in brain
      heart infusion broth for 3 weeks. An equal thickness of AH Plus, Endosequence BC
      sealer (BC sealer), and pulp canal sealer EWT (PCEWT) was placed on the root
      canal wall of the dentin specimens for 1, 7, and 30 days in humid conditions at
      37 degrees C. Gutta-percha and water were used in a similar manner as the tested
      sealers. The proportions of dead and live bacteria inside the dentinal tubules
      after exposure to root canal sealers were assessed by confocal laser scanning
      microscopy. RESULTS: Significantly more bacteria were killed in the 3 sealer
      groups than in the 2 control groups (P < .05). BC sealer and AH Plus resulted in
      significantly more dead cells than PCEWT did. There was no statistically
      significant difference between BC sealer and AH Plus at any time point (P > .05).
      Thirty days of exposure to BC sealer and AH Plus resulted in significantly more
      dead bacteria in dentin than 7-day and 1-day exposures in the biofilms, whereas
      no statistically significant increase of the proportion of dead bacteria was
      detected between 7-day and 30-day PCEWT (P > .05). CONCLUSIONS: The 3 endodontic
      root canal sealers had antibacterial effects against E. faecalis in the dentinal
      tubules. BC sealer and AH Plus had superior antibacterial effects compared with
      PCEWT. The antibacterial effects of sealers in dentinal tubules continued after
      setting.

PMID- 24666901
TI  - Effect of long-term exposure to endodontic disinfecting solutions on young and
      old Enterococcus faecalis biofilms in dentin canals.
AB  - INTRODUCTION: The purpose of this study was to evaluate the antimicrobial
      activity on Enterococcus faecalis biofilms in dentin canals of short-term and
      long-term exposure to different endodontic disinfecting solutions by using a
      dentin infection model and confocal laser scanning microscopy. METHODS: Dentinal
      tubules in semi-cylindrical dentin blocks were filled with E. faecalis by
      centrifugation and incubated to form 1-day-old and 3-week-old biofilms. The young
      and mature biofilms in dentin were subjected to sterile water, 2% chlorhexidine,
      2% sodium hypochlorite (NaOCl), and 6% NaOCl for 3, 10, and 30 minutes. After
      treatments, the proportion of bacteria killed by the disinfectants was analyzed
      by confocal laser scanning microscopy by using LIVE/DEAD bacterial viability
      stain. RESULTS: The proportion of killed bacteria was lower after 3 minutes than
      after 10 and 30 minutes of exposure to the disinfecting agents (P < .05). The
      killing of bacteria in the E. faecalis biofilms was fastest during the first 3
      minutes and slowed down greatly after 10 minutes. Six percent NaOCl was the most
      effective antibacterial solution against both the 1-day-old and 3-week-old
      biofilms (P < .05). No significant difference in bacterial killing was detected
      between 2% chlorhexidine and 2% NaOCl (P > .05). Significantly more cells were
      killed in young biofilms than in old biofilms in all groups (P < .05).
      CONCLUSIONS: The killing of bacteria in infected dentin by disinfecting solutions
      is time-dependent. However, little additional killing is obtained after the first
      10 minutes of exposure.

PMID- 24666902
TI  - Histologic examinations of teeth treated with 2 scaffolds: a pilot animal
      investigation.
AB  - INTRODUCTION: A growing body of evidence is building a case for the possibility
      of tissue regeneration within the root canal of necrotic teeth, allowing for
      continued root development. However, it remains unknown what type of tissue is
      produced after regenerative endodontics. The purpose of this study was to use
      blood clots and platelet-rich plasma (PRP) as scaffolds in regenerative
      endodontics under ideal conditions in a ferret model to examine the tissues
      generated within the root canals. METHODS: The pulps of 21 canine teeth from 7
      young ferrets were extirpated using broaches without filing the canal walls.
      Bleeding was stimulated from the periapical tissues, and a blood clot was induced
      in the canal space to the level of the cementoenamel junction in 12 teeth. PRP
      was prepared and placed in the canals to the level of the cementoenamel junction
      in 9 teeth. The coronal access was sealed with mineral trioxide aggregate. Seven
      canines were not operated on and served as controls. Three months later, block
      sections including each canine and its surrounding tissues were removed for
      histologic evaluation. The tissues found in the canals of experimental teeth were
      compared with those in the control teeth. RESULTS: Almost all of the experimental
      teeth showed the presence of intracanal bonelike tissue. No evidence of dentinal
      wall thickening or apical narrowing was noted in the experimental teeth.
      CONCLUSIONS: In this experimental model, the use of either PRP or blood clots
      during regenerative endodontics leads to the formation of intracanal bonelike
      tissue without continual root maturation.

PMID- 24666903
TI  - Effect of dentin conditioning with intracanal medicaments on survival of stem
      cells of apical papilla.
AB  - INTRODUCTION: Regenerative endodontics is a valuable treatment modality for
      immature teeth with pulpal necrosis. A common feature in regenerative cases is
      the use of intracanal medicaments. Although these medicaments are chosen because
      of their antibacterial properties, their enduring effect on dentin (conditioning)
      and the subsequent impact on stem cell survival has never been evaluated. In this
      study, we hypothesized that triple antibiotic paste (TAP), double antibiotic
      paste (DAP), or Ca(OH)2 has an indirect adverse effect on the survival of stem
      cells of apical papilla (SCAP) by dentin conditioning. METHODS: Human dentin
      disks were created with a standardized root canal diameter of 3.2 mm. The disks
      were then exposed to either TAP or DAP (at concentrations of 1 mg/mL or 1000
      mg/mL), Ca(OH)2 (Ultracal), or Hank's balanced salt solution for 7 or 28 days.
      Next, the medicaments were removed with copious irrigation, followed by placement
      of SCAP in a Matrigel scaffold in the lumen of the disks. The bioengineered
      constructs were cultured for 7 days, followed by determination of cellular
      viability by using the CellTiter-Glo luminescence assay. Data were analyzed using
      1-way analysis of variance with Bonferroni post hoc test. RESULTS: Exposure of
      dentin to TAP or DAP at 1000 mg/mL resulted in no viable SCAP, whereas the use of
      these medicaments at 1 mg/mL had no adverse effect on cell viability. In
      contrast, Ca(OH)2 treatment significantly increased SCAP survival and
      proliferation when compared with the control group. CONCLUSIONS: Dentin
      conditioning with TAP and DAP at commonly used clinical concentration
      (approximately 1000 mg/mL) alters dentin in such a way as to prevent SCAP
      survival. This lethal indirect effect of both TAP and DAP can be largely avoided
      if these medicaments are used at the 1 mg/mL concentration. Conversely, dentin
      conditioning with Ca(OH)2 promotes SCAP survival and proliferation.

PMID- 24666904
TI  - Assessment of apically extruded debris produced by the self-adjusting file
      system.
AB  - INTRODUCTION: This study was designed to quantitatively evaluate the amount of
      apically extruded debris by the Self-Adjusting-File system (SAF; ReDent-Nova,
      Ra'anana, Israel). Hand and rotary instruments were used as references for
      comparison. METHODS: Sixty mesial roots of mandibular molars were randomly
      assigned to 3 groups (n = 20). The root canals were instrumented with hand files
      using a crown-down technique. The ProTaper (Dentsply Maillefer, Ballaigues,
      Switzerland) and SAF systems were used according to the manufacturers'
      instructions. Sodium hypochlorite was used as an irrigant, and the apically
      extruded debris was collected in preweighted glass vials and dried afterward. The
      mean weight of debris was assessed with a microbalance and statistically analyzed
      using 1-way analysis of variance and the post hoc Tukey multiple comparison test.
      RESULTS: Hand file instrumentation produced significantly more debris compared
      with the ProTaper and SAF systems (P < .05). The ProTaper system produced
      significantly more debris compared with the SAF system (P < .05). CONCLUSIONS:
      Under the conditions of this study, all systems caused apical debris extrusion.
      SAF instrumentation was associated with less debris extrusion compared with the
      use of hand and rotary files.

PMID- 24666905
TI  - Setting time affects in vitro biological properties of root canal sealers.
AB  - INTRODUCTION: Biocompatibility of root canal sealers is important because of the
      long-term contact of their eluates and/or degradation products with periapical
      tissues. The literature still lacks studies about the genotoxic effects of these
      materials and the influence of setting time on biological properties. The
      cytotoxicity and genotoxicity of an epoxy resin-based sealer (AH Plus), a single
      methacrylate-based sealer (EndoRez), and a silicone-based sealer (RoekoSeal) were
      assessed. METHODS: Chinese hamster fibroblasts (V79) were cultured and exposed to
      different dilutions of extracts from the sealers that were left to set for 0, 12,
      and 24 hours before contact with culture medium. Cell viability was measured by
      the methyl-thiazol-diphenyltetrazolium assay. Genotoxicity was assessed by the
      comet assay. Data were statistically analyzed by Kruskal-Wallis and Dunn tests (P
      < .05). RESULTS: Root canal sealers were statistically more cytotoxic than the
      untreated control group, except for the silicon-based sealer. Cell viability
      ranking was the following (from the most to the least cytotoxic): methacrylate
      based > epoxy resin-based > silicone-based. The setting time influenced the epoxy
      resin-based sealer cytotoxicity (decreased at 12 hours) and the general
      genotoxicity (increased at 24 hours). DNA damage ranking was the following (from
      the most to the least genotoxic): methacrylate-based > silicone-based = epoxy
      resin-based. CONCLUSIONS: The setting time had influence on the cytotoxicity of
      the epoxy resin-based sealer and genotoxicity of all tested sealers. The
      methacrylate-based sealer was the most cytotoxic, and the silicone-based sealer
      was not cytotoxic. Genotoxicity was observed for all sealers.

PMID- 24666906
TI  - A new method to assess available chlorine in small volumes of liquid.
AB  - INTRODUCTION: There is no robust and simple way to quantify available chlorine
      from small volumes such as human root canals. Therefore, a new method was
      developed and assessed. METHODS: Standardized size-40 paper points were soaked in
      a 15% (w/v) potassium iodide solution for 1 minute. Subsequently, the paper
      points were placed in an incubator and dried at 110 degrees C for 4 hours. The
      paper points (n = 5 per measurement) were then dipped in different concentrations
      of NaOCl and photographed under standardized conditions in RAW format. The
      pictures were imported to image processing software and adjusted to the
      standardized background. The red, green, and blue levels of the paper points were
      assessed at a predefined area. Inverse regression was used to determine NaOCl
      concentration from red, green, and blue values, with both explanatory and outcome
      variables log-transformed to base 10. RESULTS: The red value measurements were
      chosen for further analysis based on a comparison of the coefficient of
      determination (R(2)) and a residual analysis. The method was applied to
      concentrations of NaOCl between 0.0001% and 1% (R(2) = 0.92). In this range,
      NaOCI concentrations could be assessed with an error not larger than 3-fold the
      determined concentration. CONCLUSIONS: The present method proved to be robust to
      determine the order of magnitude of available chlorine that is present in a small
      volume. This should be useful for endodontic research.

PMID- 24666907
TI  - Histopathological condition of the remaining tissues after endodontic infection
      of rat immature teeth.
AB  - INTRODUCTION: Recently, case reports have shown that immature teeth diagnosed
      with necrotic pulp and periapical periodontitis can be repaired through a
      regenerative endodontic procedure. True regeneration depends on the presence of
      stem cells in the remaining vital tissues. The aim of this study was to evaluate
      the histologic condition of the pulp tissue, root apical papilla, and periapical
      tissues after inducing endodontic infection in immature rat teeth for different
      periods. METHODS: This study evaluated 18 first upper rat molars (36 roots).
      Periapical lesions were induced and were confirmed radiographically, and the
      animals were divided into 3 groups according to the days of pulp exposure for
      endodontic infection induction: 30, 60, and 90 days. Histologic analysis was
      performed in 5 different areas (ie, cervical, middle, and apical root canal
      thirds; the apical papilla; and the periapex surrounding the apical papilla).
      RESULTS: At 30 days, one third of the specimens still showed vital but intensely
      inflamed pulp tissue in the apical third and vital apical papilla with varying
      degrees of inflammation. After 60 days, the results were similar with respect to
      the apical pulp tissue and apical papilla. Completely necrotic pulp tissue in the
      space canal and vital apical papilla were observed in about 67% of the cases
      after 90 days. CONCLUSIONS: Vital pulp tissue was observed in the apical third
      until 60 days and in the vital apical papilla until 90 days of infection in a rat
      model.

PMID- 24666908
TI  - Efficacy of 2 reciprocating systems compared with a rotary retreatment system for
      gutta-percha removal.
AB  - INTRODUCTION: The maximum removal of root canal filling material is essential for
      successful endodontic retreatment. The purpose of this study was to assess the
      efficacy of 2 reciprocating systems (Reciproc [VDW, Munich, Germany] and WaveOne
      [Dentsply Maillefer, Ballaigues, Switzerland]) compared with a nickel-titanium
      (NiTi) rotary system (ProTaper Universal Retreatment [Dentsply Maillefer]) in the
      removal of root canal filling material. METHODS: Sixty root canals of extracted
      human maxillary incisors were prepared using the NiTi ProTaper rotary system with
      the complementary use of a #40 K-type file and then obturated. The specimens were
      divided into 3 groups (n = 20) according to the system used for filling removal:
      group 1: instrument R25 of the Reciproc system, group 2: primary instrument of
      the WaveOne system, and group 3: NiTi rotary instruments of the ProTaper
      Universal Retreatment system. The teeth were cleaved longitudinally and
      photographed under a dental operating microscope with 5 * magnification. Images
      were transferred to a computer, and residual filling material was quantified
      using Image Tool software (University of Texas Health Science Center, San
      Antonio, TX). Results were compared using 1-way analysis of variance (P < .05).
      RESULTS: All teeth examined had filling remnants within the canal. No
      statistically significant difference (P > .05) in residual filling material was
      observed among the groups, with 4.30% in group 1, 2.98% in group 2, and 3.14% in
      group 3. CONCLUSIONS: The Reciproc and WaveOne reciprocating systems were as
      effective as the ProTaper Universal retreatment system for gutta-percha and
      sealer removal.

PMID- 24666909
TI  - Influence of operator's experience on root canal shaping ability with a rotary
      nickel-titanium single-file reciprocating motion system.
AB  - INTRODUCTION: The aim of this study was to evaluate the influence of the
      operator's experience on the shaping of double-curvature simulated root canals
      with a nickel-titanium single-file reciprocating motion system. METHODS: Sixty
      double-curvature root canals simulated in methacrylate blocks were prepared by 10
      students without any experience in endodontics and by 10 professionals who had
      studied endodontics at the postgraduate level. The Reciproc-VDW system's R25 file
      was used in the root canal preparation. The blocks were photographed before and
      after the instrumentation, and the time of instrumentation was also evaluated.
      Changes in root canal dimensions were analyzed in 6 positions. RESULTS:
      Significant differences (P < .05) were found in the apical transport of the first
      root canal curvature, with a larger percentage of increase of the root canal
      occurring in the novice group than in the expert one, as well as in the canal
      deviation at the beginning of the curvatures, whereas no significant results were
      obtained in the growth rate of the canal area. There was difference in the time
      of instrumentation, with 3.76 minutes observed in the novice group, as opposed to
      2.05 minutes in the expert group. CONCLUSIONS: The use of the single-file
      reciprocating motion system Reciproc is not seen to be influenced by the
      operator's experience regarding the increase of the canal area. Previous training
      and the need to acquire experience are important in the use of this system, in
      spite of its apparent simplicity.

PMID- 24666910
TI  - Fracture strength of roots instrumented with self-adjusting file and the ProTaper
      rotary systems.
AB  - INTRODUCTION: The purpose of this study was to evaluate the fracture strength of
      roots instrumented with the Self-Adjusting File (SAF; ReDent-Nova, Ra'anana,
      Israel) and the ProTaper system (Dentsply Maillefer, Ballaigues, Switzerland) and
      filled with the cold lateral compaction technique. METHODS: In total, 50
      mandibular premolar teeth were sectioned at or below the cementoenamel junction
      to obtain roots 13 mm in length. The roots were balanced with respect to
      buccolingual-mesiodistal diameters and weight. They were distributed into 4
      experimental groups and 1 control group (n = 10): no instrumentation (control
      group), instrumentation with ProTaper rotary files but no filling (PT),
      instrumentation with ProTaper rotary files and filling with cold lateral
      compaction (PT filling), instrumentation with SAF but no filling (SAF), and
      instrumentation with SAF and filling with cold lateral compaction (SAF filling).
      AH Plus sealer (Dentsply DeTrey, Konstanz, Germany) was used along with gutta
      percha points. One week later, a vertical load was applied to the specimen's
      canal until fracture occurred. Data were statistically analyzed using 1-way
      analysis of variance (P = .05). RESULTS: The mean fracture load was 244 +/- 51 N
      for the control group, 226 +/- 21 N for the PT, 242 +/- 45 N for PT filling, 233
      +/- 14 N for the SAF, and 271 +/- 44 N for SAF filling. However, the differences
      were not statistically significant (P > .05). CONCLUSIONS: Instrumentation with
      the SAF or the ProTaper rotary system did not change the fracture strength of
      standardized roots with respect to cross-sectional diameter and weight.

PMID- 24666911
TI  - Investigation of the effect of sealer use on the heat generated at the external
      root surface during root canal obturation using warm vertical compaction
      technique with System B heat source.
AB  - INTRODUCTION: During warm vertical compaction of gutta-percha, root canal sealers
      with different chemical compositions absorb the heat generated inside the root
      canal. The aim of this research was to assess physicochemical modifications of
      sealers subjected to the System B heat source (Analytic Technology, Redmond, WA)
      and to evaluate the effect that the use of different sealers has on the heat
      transfer to the external root surface. METHODS: Three proprietary brand sealers
      (AH Plus [Dentsply International, Addlestone, UK], Pulp Canal Sealer [Kerr
      Corporation, Orange, CA], MTA Fillapex [Angelus Dental Solutions, Londrina, PR,
      Brazil]) and a prototype sealer based on Portland cement were assessed. The heat
      generated on the surfaces of System pluggers and the heat dissipation at
      different levels (apical, midroot, and cervical) over root surface while using
      different sealers was assessed using thermocouples. Data were collected in 3
      different environmental conditions with the tooth suspended in air, immersed in
      Hank's balanced salt solution, or gelatinized Hank's balanced salt solution.
      Chemical changes in the sealers induced by the heat were monitored by Fourier
      transform infrared spectroscopy. The effect of heat changes on the setting time
      and compressive strength of the sealers was also assessed. RESULTS: The
      continuous wave plugger sustained a rise in temperature at a maximum of 80
      degrees C at the instrument shank. The highest change in temperature on the
      external root surface was recorded after 1.5 minutes from the start of heating,
      and it was restored to body temperature by 6 minutes. Environmental conditions
      affected heat dissipation for all the sealers in the midroot and cervical regions
      and the highest increase in temperature (~60 degrees C) recorded in air. In the
      midroot and cervical regions, the type of sealer used did not affect the rise in
      temperature. In the apical region, AH Plus obturations resulted in a greater rise
      in temperature, and the chemical composition of this sealer was affected by high
      temperature; it also induced a reduction in sealer setting time and strength.
      CONCLUSIONS: It could be concluded that surrounding conditions, such as
      temperature and humidity, exerted influence on heating dissipation during the
      continuous wave of the condensation obturation technique and that root canal
      sealers presented different conductive/isolating properties. Furthermore, the
      physical and chemical properties of AH Plus were negatively affected by the
      changes in temperature.

PMID- 24666912
TI  - Effect of fatigue on torsional failure of nickel-titanium controlled memory
      instruments.
AB  - INTRODUCTION: The purpose of this study was to understand how fatigue affects the
      torsional properties of both traditional nickel-titanium (NiTi) and NiTi
      controlled memory (CM) files. METHODS: Typhoon (TYP; Clinician's Choice Dental
      Products, New Milford, CT) 25/.04 and 40/.04 rotary files in both NiTi and CM
      were tested to obtain the mean number of cycles of failure (Nf) using a 3-point
      bending apparatus. New files were then precycled to 4 conditions (0%, 25%, 50%,
      and 75% of the Nf), and torsional resistance tests were performed. Each file was
      exposed to torsional stress until failure, and at that point the torque and
      distortion angles were measured. The fracture surface of each fragment was
      examined with a scanning electron microscope. RESULTS: TYP CM files had an Nf 7
      times higher than that of TYP files (P < .05). No difference in torque between
      the CM files and the conventional NiTi files of either file size was detected (P
      > .05). The torque of the size 40/.04 files was significantly higher than the
      torque of the size 25/.04 files (P < .05). In the 40/.04 files group, TYP files
      in the 75% precycling group had a significantly lower torque than files in the
      group with no precycling (P < .05), whereas slight precycling (25%) significantly
      reduced the distortion angle on TYP CM files (P < .05). The CM files of both
      sizes had a significantly higher distortion angle than the corresponding NiTi
      files (P < .05). The fractured files in the precycling groups showed the typical
      pattern of torsional failure. CONCLUSIONS: Within the same amount of precycling
      (25%, 50%, and 75%), the cyclic fatigue life of TYP CM instruments was
      significantly higher than that of the TYP instruments. However, the torque value
      of TYP CM was similar to TYP files. The larger instruments were not only less
      resistant to cyclic fatigue but were affected most by prestressing of both TYP
      and TYP CM files.

PMID- 24666913
TI  - Antibacterial efficacy of photosensitizer functionalized biopolymeric
      nanoparticles in the presence of tissue inhibitors in root canal.
AB  - INTRODUCTION: Application of antibacterial nanoparticles to improve root canal
      disinfection has received strong interest recently. The current study aims to
      assess the antibacterial effect of a novel photosensitizer (rose bengal
      functionalized chitosan nanoparticles [CSRBnp]) to eliminate bacteria in the
      presence of various root canal constituents that are known to inhibit the
      antibacterial efficacy of root canal disinfectants. METHODS: The synthesized
      CSRBnp were evaluated for size, charge, and singlet oxygen release. The
      antibacterial effect of CSRBnp was tested on planktonic Enterococcus faecalis
      with or without pretreatment by using different inhibiting agents such as dentin,
      dentin-matrix, pulp tissue, bacterial lipopolysaccharides, and bovine serum
      albumin (BSA). Bacterial survival was assessed in a time-dependent manner. The
      antibacterial effects after photodynamic activation on CSRBnp, a cationic
      photosensitizer (methylene blue), and an anionic photosensitizer (rose bengal
      [RB]) in the presence of inhibitors were also evaluated. RESULTS: CSRBnp were 60
      +/- 20 nm in size and showed reduced rate of singlet oxygen release as compared
      with methylene blue and RB. Pulp and BSA inhibited the antibacterial effect of
      CSRBnp (without photoactivation) significantly (P < .05) even after 24 hours of
      interaction. In case of photodynamic therapy, the pulp and BSA significantly
      inhibited the antibacterial activity of all 3 photosensitizers. CSRBnp showed
      residual effect and completely eliminated the bacteria after 24 hours of
      interaction after photodynamic therapy. CONCLUSIONS: The inherent antibacterial
      activity of polycationic chitosan nanoparticles and the singlet oxygen released
      after photoactivation of RB synergistically provided CSRBnp the potential to
      achieve significant antibacterial efficacy even in the presence of tissue
      inhibitors within root canals.

PMID- 24666914
TI  - Comparative assessment of the effects of Gates-Glidden, Largo, LA-Axxess, and New
      Brazilian Drill CPdrill on coronal pre-enlargement: cone-beam computed
      tomographic analysis.
AB  - INTRODUCTION: The removal of dentin interferences from the cervical third of root
      canals is essential for their correct cleaning and shaping and to facilitate
      access of endodontic instruments to the critical apical region. In mandibular
      molars, the concavity observed in the furcation area reduces dentin thickness,
      making this region more susceptible to perforation. The present ex vivo study
      used cone-beam computed tomographic imaging to compare 3 rotary burs with a new
      rotary bur recently launched in Brazil (ie, CPdrill; Helse Industry and Commerce
      Ltda, Santa Rosa, Sao Paulo, Brazil) regarding the amount of dentin removal from
      the distal wall of the mesial root of mandibular first molars. METHODS: A total
      of 40 root canals were selected and randomly divided into 4 groups for cervical
      preparation: Gates-Glidden burs #2 and #3 (Dentsply Maillefer, Ballaigues,
      Switzerland), Largo burs #1 and #2 (Dentsply Maillefer), LA-Axxess burs #1 and #2
      (SybronEndo, Glendora, CA), and CPdrill burs (1-size only). Dentin thickness in
      the distal wall of mesial canals at 2 mm from the furcation was measured using I
      CATvision software before and after cervical preparation. RESULTS: There was no
      statistically significant difference between groups regarding residual dentin
      thickness after instrumentation with the drills (P = .684). CONCLUSIONS: It was
      concluded that CPdrill is safe for use in cervical preparation of the mesial root
      of mandibular first molars because it did not promote excessive dentin removal on
      distal walls.

PMID- 24666915
TI  - Bending resistance and dynamic and static cyclic fatigue life of Reciproc and
      WaveOne large instruments.
AB  - INTRODUCTION: The aim of the present study was to evaluate the bending resistance
      and the dynamic and static cyclic fatigue life of Reciproc R40 and WaveOne large
      instruments. METHODS: A sample of 68 nickel-titanium instruments (25 mm in
      length) for use under reciprocation movement (Reciproc and WaveOne) from 3
      different lots was tested. Reciproc R40 and WaveOne Large files, both of which
      had a nominal size of 0.40 mm at D0, were selected. The bending resistance was
      performed in 10 instruments of each system by using a universal testing machine.
      Dynamic and static models for cyclic fatigue testing were performed by using a
      custom-made device. For these tests, an artificial canal measuring 1.4 mm in
      diameter and 19 mm total length was fabricated from a stainless steel tube.
      Scanning electron microscopy analysis was performed to determine the mode of
      fracture. Statistical analysis was performed by using parametric methods, 1-way
      analysis of variance. Post hoc pair-wise comparisons were performed by using
      Tukey test for multiple comparisons. RESULTS: WaveOne instruments presented
      significantly higher bending resistance than Reciproc (P < .05). Moreover,
      Reciproc revealed a significantly longer cyclic fatigue life (P < .05) in both
      static and dynamic tests (P < .05). CONCLUSIONS: Reciproc R40 instruments
      resisted dynamic and static cyclic fatigue significantly more than WaveOne Large
      instruments. Furthermore, WaveOne instruments presented significantly less
      flexibility than Reciproc.

PMID- 24666916
TI  - Cavitation measurement during sonic and ultrasonic activated irrigation.
AB  - INTRODUCTION: The aims of this study were to quantify and to visualize the
      possible occurrence of transient cavitation (bubble formation and implosion)
      during sonic and ultrasonic (UAI) activated irrigation. METHODS: The amount of
      cavitation generated around several endodontic instruments was measured by
      sonochemiluminescence dosimetry inside 4 root canal models of human dimensions
      and varying complexity. Furthermore, the spatial distribution of the
      sonochemiluminescence in the root canal was visualized with long-exposure
      photography. RESULTS: Instrument oscillation frequency, ultrasonic power, and
      file taper influenced the occurrence and amount of cavitation. In UAI, cavitation
      was distributed between the file and the wall extending beyond the file and
      inside lateral canals/isthmuses. In sonic activated irrigation, no cavitation was
      detected. CONCLUSIONS: Cavitation was shown to occur in UAI at clinically
      relevant ultrasonic power settings in both straight and curved canals but not
      around sonically oscillating instruments, driven at their highest frequency.

PMID- 24666917
TI  - Elimination of intracanal tissue and debris through a novel laser-activated
      system assessed using high-resolution micro-computed tomography: a pilot study.
AB  - INTRODUCTION: Laser-activated irrigation to remove organic debris from canal
      isthmuses was investigated using x-ray microfocus computed tomographic imaging.
      METHODS: A total of 14 extracted human mandibular molars were used. The mesial
      canals were prepared using a standardized instrumentation protocol. Two groups (n
      = 7) underwent final irrigation using either standard needle irrigation (SNI) or
      photon-induced photoacoustic streaming (PIPS). After enlarging canals to 30/.06,
      canal volumes were reconstructed from micro-computed tomographic scans before and
      after irrigation to assess removal of organic tissue and inorganic debris by
      quantitative analysis of the superimposed volumes. Comparisons of the volumes
      were made using 2-way analysis of variance and Tukey method, with statistical
      differences considered significant at the alpha = 0.05 level. RESULTS: Debris
      removal and an increase in root canal system volume for the laser-activated PIPS
      group was more significant (P < .001) than for the SNI group (P = .04).
      Irrigation using PIPS increased the canal volume and eliminated debris from the
      canal system 2.6 times greater than SNI. CONCLUSIONS: Eliminating debris from
      complex canal spaces found in mandibular molars was achieved at a significantly
      greater level using laser-activated PIPS irrigation compared with SNI.

PMID- 24666918
TI  - Regaining apical patency after obturation with gutta-percha and a sealer
      containing mineral trioxide aggregate.
AB  - INTRODUCTION: MTA Fillapex (Angelus Solucoes Odontologicas, Londrina PR, Brazil)
      was introduced as a mineral trioxide aggregate (MTA)-based sealer used for
      endodontic obturation. There is a lack of research that evaluates the ability of
      different solvents to soften MTA-based sealers during retreatment. This study
      tested the ability of 4 commonly used endodontic solvents to soften gutta-percha
      and MTA Fillapex to allow for the re-establishment of apical patency. METHODS:
      Eighty-six extracted maxillary anterior teeth were instrumented to the working
      length to a size 45 (.04 taper size). Teeth were divided into 2 groups (n = 43
      for each group). MTA Fillapex was placed into all canals. Group 1 was obturated
      with gutta-percha to the working length, and group 2 was obturated 2 mm short of
      the working length to ensure the apical 2 mm was filled with sealer only. Both
      groups were divided into 4 subgroups (n = 10). The remaining teeth served as the
      control group. Each subgroup was exposed to 1 of the following solvents:
      chloroform, Endosolv R (Septodont, Saint-Maur, France), Endosolv E (Septodont),
      or eucalyptol. RESULTS: Patency was re-established in 100% of the teeth in groups
      1 and 2 when tested with chloroform or Endosolv E, 80% of the teeth in group 1
      and 90% in group 2 when tested with eucalyptol, and 10% of the teeth in group 1
      and 50% in group 2 tested when with Endosolv R. The chi-square test indicated
      there was a statistical difference between Endosolv R and the other tested
      solvents for both groups. CONCLUSIONS: Chloroform, Endosolv E, and Eucalyptol
      soften GP and MTA Fillapex sufficiently to aid in re-establishing apical patency
      during endodontic retreatment.

PMID- 24666920
TI  - The impact of Scottish Government protocols on practice in Scotland.
AB  - Objectives: To investigate rates of septorhinoplasty and rhinoplasty in Scotland
      between 2006 and 2010, and to establish the impact of government legislation.
      Methods: Data on the rates of rhinoplasty and septorhinoplasty were collected and
      analysed according to specialty, region and year. Results: In 2006, 754
      septorhinoplasty and rhinoplasty cases were recorded (147 per million
      population), rising to 893 (171 per million population) in 2010. Mean annual
      rates per million population were 152 (87 per cent of procedures) in ENT, 13.9 (8
      per cent) in plastic surgery and 8.7 (8 per cent) in oromaxillofacial surgery.
      After 2009, there was a 43 per cent reduction in the rhinoplasty rate (p <
      0.0001), although the oromaxillofacial surgery rate increased by 68 per cent (p <
      0.05). Over the same period, the septorhinoplasty rate increased in ENT (46 per
      cent, p < 0.0001), and declined in plastic surgery (24 per cent, p = 0.49) and
      oromaxillofacial surgery (45 per cent, p = 0.05). Overall, the rate for
      rhinoplasty plus septorhinoplasty only declined by 1 per cent. There was
      significant regional variation. Conclusion: Overall, septorhinoplasty rates have
      increased and rhinoplasty rates have decreased. There was only a 1 per cent
      decrease in the overall rate following the 2009 legislation. Practice differs
      between regions.

PMID- 24666919
TI  - Maxillary premolar with 4 separate canals.
AB  - INTRODUCTION: Recognition of anatomic variations is a challenge for clinicians
      regardless of which tooth is treated. Maxillary premolars usually have 2 root
      canals, but the presence of 3 distinct root canals has been reported in 1%-6% of
      cases. METHODS AND RESULTS: This report describes the case of a maxillary right
      second premolar with 4 separate canals: 1 mesial, 1 palatal, and 2 distal canals.
      This was confirmed by using cone-beam computed tomography and was successfully
      treated with rotary files and obturated by using a warm vertical compaction
      technique. CONCLUSIONS: The clinical significance of the present case is that
      this is the first report of 3 roots and 4 separate canals in a maxillary
      premolar. Precise knowledge of root canal morphology and its variation is also
      underlined. Cone-beam computed tomography examination and the operating
      microscope are excellent tools for identifying and managing these complex root
      canal systems.

PMID- 24666921
TI  - Gilded nanoparticles for plasmonically enhanced fluorescence in TiO2:Sm3+ sol-gel
      films.
AB  - Silica-gold core-shell nanoparticles were used for plasmonic enhancement of rare
      earth fluorescence in sol-gel-derived TiO2:Sm3+ films. Local enhancement of Sm3+
      fluorescence in the vicinity of separate gilded nanoparticles was revealed by a
      combination of dark field microscopy and fluorescence spectroscopy techniques. An
      intensity enhancement of Sm3+ fluorescence varies from 2.5 to 10 times depending
      on the used direct (visible) or indirect (ultraviolet) excitations. Analysis of
      fluorescence lifetimes suggests that the locally stronger fluorescence occurs
      because of higher plasmon-coupled direct absorption of exciting light by the Sm3+
      ions or due to plasmon-assisted non-radiative energy transfer from the excitons
      of TiO2 host to the rare earth ions. PACS: 78; 78.67.-n; 78.67.Bf.

PMID- 24666922
TI  - Hypoglycaemia and QT interval prolongation in type 1 diabetes--bridging the gap
      between clamp studies and spontaneous episodes.
AB  - AIMS: We propose a study design with controlled hypoglycaemia induced by
      subcutaneous injection of insulin and matched control episodes to bridge the gap
      between clamp studies and studies of spontaneous hypoglycaemia. The observed
      prolongation of the heart rate corrected QT interval (QTc) during hypoglycaemia
      varies greatly between studies. METHODS: We studied ten adults with type 1
      diabetes (age 41+/-15years) without cardiovascular disease or neuropathy. Single
      blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a
      control episode on two occasions separated by 4weeks. QT intervals were measured
      using the semi-automatic tangent approach, and QTc was derived by Bazett's (QTcB)
      and Fridericia's (QTcF) formulas. RESULTS: QTcB increased from baseline to
      hypoglycaemia (403+/-20 vs. 433+/-39ms, p<0.001). On the euglycaemia day, QTcB
      also increased (398+/-20 vs. 410+/-27ms, p<0.01), but the increase was less than
      during hypoglycaemia (p<0.001). The same pattern was seen for QTcF. Plasma
      adrenaline levels increased significantly during hypoglycaemia compared to
      euglycaemia (p<0.01). Serum potassium levels decreased similarly after insulin
      injection during both hypoglycaemia and euglycaemia. CONCLUSIONS: Hypoglycaemia
      as experienced after a subcutaneous injection of insulin may cause QTc
      prolongation in type 1 diabetes. However, the magnitude of prolongation is less
      than typically reported during glucose clamp studies, possible because of the
      study design with focus on minimizing unwanted study effects.

PMID- 24666923
TI  - Sudden cardiac death and diabetes mellitus.
AB  - Sudden cardiac death (SCD) affects a significant percentage of diabetic patients.
      SCD in these patients can be due to several factors, such as diastolic
      dysfunction, heart failure, altered platelet function, inflammation, sympathetic
      nervous stimulation and other factors. In the present review, we discuss the
      association between diabetes mellitus and SCD. 

PMID- 24666924
TI  - Thrombus in the left atrial appendage: a case report of neonate.
AB  - A Japanese girl first pointed out the mass in the left atrial appendage by the
      echocardiography on the 3rd day of life. At 30th day of life, the mass in the
      left atrial appendage was excised en bloc successfully under cardiopulmonary
      bypass because it appeared mobile. Its pathologic finding revealed an old
      organised thrombus. She is doing well with no episode of thrombus formation or
      thromboembolism, 2 years postoperatively. 

PMID- 24666925
TI  - Health-related quality of life and functionality in elderly men and women before
      and after a fall-related wrist fracture.
AB  - AIMS: To evaluate health-related quality of life (HRQoL) and functionality among
      older men and women who suffered a wrist fracture because of a fall and to
      identify postfracture consequences. METHODS: Observational, prospective cohort
      study of patients recruited in the emergency departments (ED) of six public
      hospitals of the Basque Health Service and one of the Catalan Health Service. Two
      groups of adults aged 65 or older were recruited: 960 with wrist fractures
      because of falls (fracture cohort) and 119 without fall-related wrist fractures
      in the previous year (non-fracture cohort). We collected sociodemographical and
      clinical data; general and specific HRQoL data measured by the 12-Item Short Form
      Health Survey (SF-12) and a short version of the Disabilities of the Arm,
      Shoulder, and Hand instrument (QuickDASH); and data about basic (BADL) and
      instrumental (IADL) activities of daily living, measured by the Barthel Index and
      the Lawton and Brody Index (LBI). RESULTS: Women with wrist fractures exhibited
      greater declines than men 6 months after the fall in all questionnaires except
      the LBI, and greater declines than those in the non-fracture cohort independent
      of gender. Patients aged 80 years and older presented with worse baseline scores
      in all the outcome measures and lost more HRQoL and functionality after wrist
      fractures. DISCUSSION: Women and older individuals experienced the greatest
      reductions in HRQoL and functionality after a fall-related wrist facture,
      suggesting that they might merit special attention in clinical care and public
      health policy. CONCLUSIONS: Specific prevention strategies may be needed to avoid
      or reduce the consequences of fall-related wrist fractures.

PMID- 24666926
TI  - Magnitude and risk factors of abortion among regular female students in Wolaita
      Sodo University, Ethiopia.
AB  - BACKGROUND: Induced abortion is one of the greatest human rights dilemmas of our
      time. Yet, abortion is a very common experience in every culture and society.
      According to the World Health Organization, Ethiopia had the fifth largest number
      of maternal deaths in 2005 and unsafe abortion was estimated to account for 32%
      of all maternal deaths in Ethiopia. Youth are disproportionately affected by the
      consequences of unsafe abortion. The objective of this study was, therefore, to
      determine the magnitude and identify factors associated with abortion among
      female Wolaita Sodo University students. METHODS: A descriptive, cross-sectional
      study was conducted in Wolaita Sodo University between May and June 2011. Data
      were collected from 493 randomly selected female students using structured and
      pre-tested questionnaires. RESULTS: The rate of abortion among students was found
      to be 65 per 1000 women, making it three fold the national rate of abortion for
      Ethiopia (23/1000 women aged 15-44). Virtually all of the abortions (96.9%) were
      induced and only half (16) were reported to be safe. Students with history of
      alcohol use, who are first-year and those enrolled in faculties with no post
      Grade 10 Natural Science background had higher risk of abortion than their
      counterparts. About 23.7% reported sexual experience. Less than half of the
      respondents (44%) ever heard of emergency contraception and only 35.9% of those
      who are sexually experienced ever used condom. CONCLUSIONS: High rate of abortion
      was detected among female Wolaita Sodo University students and half of the
      abortions took place/initiated under unsafe circumstances. Knowledge of students
      on legal and safe abortion services was found to be considerably poor. It is
      imperative that improved sexual health education, with focus on safe and legal
      abortion services is rendered and wider availability of Youth Friendly family
      planning services are realized in Universities and other places where young men
      and women congregate.

PMID- 24666927
TI  - High level of molecular and phenotypic biodiversity in Jatropha curcas from
      Central America compared to Africa, Asia and South America.
AB  - BACKGROUND: The main bottleneck to elevate jatropha (Jatropha curcas L.) from a
      wild species to a profitable biodiesel crop is the low genetic and phenotypic
      variation found in different regions of the world, hampering efficient plant
      breeding for productivity traits. In this study, 182 accessions from Asia (91),
      Africa (35), South America (9) and Central America (47) were evaluated at genetic
      and phenotypic level to find genetic variation and important traits for oilseed
      production. RESULTS: Genetic variation was assessed with SSR (Simple Sequence
      Repeat), TRAP (Target Region Amplification Polymorphism) and AFLP (Amplified
      fragment length polymorphism) techniques. Phenotypic variation included seed
      morphological characteristics, seed oil content and fatty acid composition and
      early growth traits. Jaccard's similarity and cluster analysis by UPGM
      (Unweighted Paired Group Method) with arithmetic mean and PCA (Principle
      Component Analysis) indicated higher variability in Central American accessions
      compared to Asian, African and South American accessions. Polymorphism
      Information Content (PIC) values ranged from 0 to 0.65. In the set of Central
      American accessions. PIC values were higher than in other regions. Accessions
      from the Central American population contain alleles that were not found in the
      accessions from other populations. Analysis of Molecular Variance (AMOVA; P <
      0.0001) indicated high genetic variation within regions (81.7%) and low variation
      across regions (18.3%). A high level of genetic variation was found on early
      growth traits and on components of the relative growth rate (specific leaf area,
      leaf weight, leaf weight ratio and net assimilation rate) as indicated by
      significant differences between accessions and by the high heritability values
      (50-88%). The fatty acid composition of jatropha oil significantly differed (P <
      0.05) between regions. CONCLUSIONS: The pool of Central American accessions
      showed very large genetic variation as assessed by DNA-marker variation compared
      to accessions from other regions. Central American accessions also showed the
      highest phenotypic variation and should be considered as the most important
      source for plant breeding. Some variation in early growth traits was found within
      a group of accessions from Asia and Africa, while these accessions did not differ
      in a single DNA-marker, possibly indicating epigenetic variation.

PMID- 24666928
TI  - Reversal of English trend towards hospital death in dementia: a population-based
      study of place of death and associated individual and regional factors, 2001
      2010.
AB  - BACKGROUND: England has one of the highest rates of hospital death in dementia in
      Europe. How this has changed over time is unknown. This study aimed to analyse
      temporal trends in place of death in dementia over a recent ten year period.
      METHODS: Population-based study linking Office for National Statistics mortality
      data with regional variables, in England 2001-2010. Participants were adults aged
      over 60 with a death certificate mention of dementia. Multivariable Poisson
      regression was used to determine the proportion ratio (PR) for death in care home
      (1) and home/hospice (1) compared to hospital (0). Explanatory variables included
      individual factors (age, gender, marital status, underlying cause of death), and
      regional variables derived at area level (deprivation, care home bed provision,
      urbanisation). RESULTS: 388,899 deaths were included. Most people died in care
      homes (55.3%) or hospitals (39.6%). A pattern of increasing hospital deaths
      reversed in 2006, with a subsequent decrease in hospital deaths (-0.93% per year,
      95% CI -1.08 to -0.79 p < 0.001), and an increase in care home deaths (0.60% per
      year, 95% CI 0.45 to 0.75 p < 0.001). Care home death was more likely with older
      age (PR 1.11, 1.10 to 1.13), and in areas with greater care home bed provision
      (PR 1.82, 1.79 to 1.85) and affluence (PR 1.29, 1.26 to 1.31). Few patients died
      at home (4.8%) or hospice (0.3%). Home/hospice death was more likely in affluent
      areas (PR 1.23, 1.18 to 1.29), for women (PR 1.61, 1.56 to 1.65), and for those
      with cancer as underlying cause of death (PR 1.84, 1.77 to 1.91), and less likely
      in the unmarried (PRs 0.51 to 0.66). CONCLUSIONS: Two in five people with
      dementia die in hospital. However, the trend towards increasing hospital deaths
      has reversed, and care home bed provision is key to sustain this. Home and
      hospice deaths are rare. Initiatives which aim to support the end of life
      preferences for people with dementia should be investigated.

PMID- 24666929
TI  - Effects of music on complications during hemodialysis for chronic renal failure
      patients.
AB  - The study was planned as a case-control study to examine the effects of music on
      some of the complications experienced by chronic renal failure (CRF) patients
      during hemodialysis. A total of 60 patients (30 intervention and 30 control)
      diagnosed with end-stage renal failure undergoing hemodialysis treatment
      participated in this study. The study was conducted in Manisa Merkez Efendi State
      Hospital Hemodialysis Unit and Manisa Ozel Anemon Hemodialysis between April 2012
      and July 2012. The intervention group listened 30 minutes in each session (12
      total sessions) Turkish art music at the beginning of the third hour of their
      hemodialysis sessions. Patient Information Form and visual analog scale to assess
      pain, nausea, vomiting, and cramps during hemodialysis session were used. For the
      analysis of data, the number, percentage, chi-square test, and significance test
      of independent group differences between two averages were conducted. According
      to the findings of the study, the average of the intervention and control group
      ages, respectively, was 50.86 +/- 11.3 and 55.13 +/- 9.68. The primary duration
      of hemodialysis treatment for both intervention and control groups was "1 year
      and above" (70.0%). The intervention group's pain and nausea scores were lower
      than the control group for all 12 sessions. The difference between the
      intervention and the control group's pain scores was significant (P < 0.05).
      However, in pain scores from the first session to 12th session, continuous
      decreasing trend was not observed. According to the results, music can be used as
      an independent nursing practice for reduction of complications for CRF patients
      receiving hemodialysis treatment. 

PMID- 24666930
TI  - First confirmation of imported dengue virus serotype 2 complete genome in urine
      from a Chinese traveler returning from India.
AB  - Dengue virus (DENV) is a mosquito-borne virus that has four serotypes. Collection
      of serum from patients is time- and labor- consuming, and presents a high injury
      risk for infants and children. The genomic and serological diagnosis of imported
      dengue fever from a urine sample was used as a non-invasive diagnostic method in
      this study. A serum sample was collected on disease day 5, and a serum and urine
      sample were collected on disease day 8 and 18. The results of serological tests
      for DENV IgM revealed that the serum samples were positive for DENV. The results
      of RT-qPCR assay revealed that the serum sample collected on day 5 was DENV
      positive; however, the serum sample collected on day 8 and 18 were negative for
      DENV. The urine sample collected on day 8 and 18 were DENV-positive. We also
      sequenced the complete DENV genome (10723 bp) from the urine sample (GenBank
      KF479233). The results of phylogenetic and epidemiological analysis indicated
      strong confirmation that the strain was located within the DENV-2 group with a
      100% bootstrap value. In this report, we (1) provided the first evidence of a
      DENV infection that was imported from India to a non-endemic city of China, (2)
      investigated the DENV genome detection having a longer timeframe for positive
      detection in urine sample compared to previous studies, (3) provided the sequence
      results for the complete DENV-2 genome from a concentrated urine sample (4)
      discussed how virus-typing results could be used to manage the risk of sero
      specific and re-infected travel-associated dengue fever. 

PMID- 24666931
TI  - Comparison of the modified shuttle walk test and cardiopulmonary exercise test in
      sarcoidosis.
AB  - BACKGROUND AND OBJECTIVE: Dyspnoea and exercise intolerance are common in
      sarcoidosis and are often poorly correlated with resting lung function.
      Measurement of peak exercise capacity is likely to be helpful in assessing and
      monitoring disease. The aim of this study was to compare the modified shuttle
      walk test (MSWT) to cardiopulmonary exercise test (CPET) as a measure of peak
      exercise capacity in sarcoidosis. METHODS: Thirty-three (17 male, mean age 48
      years) patients with sarcoidosis completed a standardized exponential exercise
      protocol cycle ergometer CPET and a single corridor MSWT in random order.
      RESULTS: Subjects has a mean forced expiratory volume in 1 s (FEV1) 2.4 L
      (75.7%predicted), forced vital capacity (FVC) 3.43 L (88.7%predicted) and
      diffusing capacity for carbon monoxide (DLCO) 20.3 mL/min/mm Hg (71.4%predicted).
      There was a strong correlation between MSWT distance and peak oxygen uptake (VO2)
      during CPET (r = 0.87; P < 0.0001), and between maximum heart rate during MSWT
      and CPET (r = 0.82; P < 0.0001). There was a moderate correlation between FEV1 ,
      FVC and DLCO with MSWT distance (r = 0.55, r = 0.61, r = 0.61, respectively; all
      P < 0.001) and with peak VO2 (r = 0.62, r = 0.63, r = 0.62, respectively; all P <
      0.0001). CONCLUSIONS: Peak VO2 achieved during CPET strongly correlated with MSWT
      distance. MSWT is a measure of peak exercise capacity in sarcoidosis that does
      not require equipment and can be readily available in the clinic.

PMID- 24666932
TI  - The role of incretin-based therapies in prediabetes: a review.
AB  - Prediabetes, a high-risk state for future development of diabetes, is prevalent
      globally. Abnormalities in the incretin axis are important in the progression of
      B-cell failure in type 2 diabetes. Incretin based therapy was found to improve B
      cell mass and glycaemic control in addition to having multiple beneficial effects
      on the systolic and diastolic blood pressure, weight loss in addition to their
      other beneficial effects on the liver and cardiovascular system. In prediabetes,
      several well-designed preventive trials have shown that lifestyle and
      pharmacologic interventions such as metformin, thiazolidinediones (TZD), acarbose
      and, nateglinide and orlistat, are effective in reducing diabetes development. In
      recent small studies, incretin based therapy (DPP IV inhibitors and GLP-1
      agonists) have also been extended to patients with prediabetes since it was shown
      to better preserve B-cell function and mass in animal studies and in clinical
      trials and it was also shown to help maintain good long term metabolic control.
      Because of the limited studies and clinical experience, their side effects and
      costs currently guidelines do not recommend incretin-based therapies as an option
      for treatment in patients with prediabetes. With future clinical trials and
      studies they may be recommended for patients with impaired fasting glucose or
      impaired glucose tolerance. 

PMID- 24666933
TI  - Does surgery influence the outcome of Aspergillus osteomyelitis?

PMID- 24666934
TI  - Clavulanic acid production estimation based on color and structural features of
      Streptomyces clavuligerus bacteria using self-organizing map and genetic
      algorithm.
AB  - The utilization of antibiotics produced by Clavulanic acid (CA) is an increasing
      need in medicine and industry. Usually, the CA is created from the fermentation
      of Streptomycen Clavuligerus (SC) bacteria. Analysis of visual and morphological
      features of SC bacteria is an appropriate measure to estimate the growth of CA.
      In this paper, an automatic and fast CA production level estimation algorithm
      based on visual and structural features of SC bacteria instead of statistical
      methods and experimental evaluation by microbiologist is proposed. In this
      algorithm, structural features such as the number of newborn branches, thickness
      of hyphal and bacterial density and also color features such as acceptance color
      levels are extracted from the SC bacteria. Moreover, PH and biomass of the medium
      provided by microbiologists are considered as specified features. The level of CA
      production is estimated by using a new application of Self-Organizing Map (SOM),
      and a hybrid model of genetic algorithm with back propagation network (GA-BPN).
      The proposed algorithm is evaluated on four carbonic resources including malt,
      starch, wheat flour and glycerol that had used as different mediums of bacterial
      growth. Then, the obtained results are compared and evaluated with observation of
      specialist. Finally, the Relative Error (RE) for the SOM and GA-BPN are achieved
      14.97% and 16.63%, respectively. 

PMID- 24666935
TI  - Confirmation of 13 sulfonamides in honey by liquid chromatography-tandem mass
      spectrometry for monitoring plans: validation according to European Union
      Decision 2002/657/EC.
AB  - A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the simultaneous confirmation of 13 sulfonamides in honey was
      developed and fully validated in accordance with the European Commission Decision
      No 2002/657/EC. The validation scheme was built in accordance with the target
      level of 50MUgkg(-1) for all analytes. The sulfonamides investigated were as
      follows: sulfaguanidine (SGN), sulfanilamide (SNL), sulfadiazine (SDZ),
      sulfathiazole (STZ), sulfamerazine (SMR), sulfamethizole (SMZ), sulfadimerazine
      (SDM), sulfamonomethoxine (SMNM), sulfamethoxypiridazine (SMP), sulfadoxine
      (SDX), sulfamethoxazole (SMX), sulfaquinoxaline (SQX) and sulfadimethoxine (SDT).
      Several extraction procedures were investigated during the development phase.
      Finally, the best results were obtained with a procedure using acidic hydrolysis
      and cation exchange purification. Chromatographic separation was achieved on a
      C18 analytical column. Matrix effects were also investigated. Data acquisition
      implemented for the confirmatory purpose was performed by monitoring 2 MRM
      transitions per analyte under the positive electrospray mode. Mean relative
      recoveries ranged from 85.8% to 110.2% and relative standard deviations lying
      between 2.6% and 19.8% in intra-laboratory reproducibility conditions. The
      decision limits (CCalpha) ranged from 1.8 to 15.5MUgkg(-1). High resolution mass
      spectrometry was used to investigate the possible formation of sulfonamide
      metabolites in honey. The validation results proved that the method is suitable
      for the screening and confirmatory steps as implemented for the French monitoring
      residue plan for sulfonamides residue control in honeybees. 

PMID- 24666936
TI  - Coacervative extraction as a green technique for sample preparation for the
      analysis of organic compounds.
AB  - One of the present trends in analytical chemistry is miniaturization, which is
      one of the methods of green analytical chemistry application. A particular
      emphasis is placed on the elimination of the use of large amounts of organic
      solvents which are toxic and harmful to the environment, maintaining high
      efficiency of the extraction process, high recovery values and low values of
      quantification (LOQ) and detection (LOD) limits. These requirements are fulfilled
      by coacervative extraction (CAE) technique. In this review, theoretical aspects
      of the coacervation process are presented along with environmental and
      bioanalytical applications of this technique, its advantages, limitations and
      competitiveness with other techniques. Due to its simplicity and rapidity, CAE is
      an excellent alternative for currently practiced procedures of sample preparation
      for the analysis of organic compounds. 

PMID- 24666937
TI  - Determination of the pore size distribution of high-performance liquid
      chromatography stationary phases via inverse size exclusion chromatography.
AB  - Stationary phases in liquid chromatography exhibit quite different pore
      structures. Whereas most of the fully porous packing materials possess a narrow
      pore size distribution, core-shell particles are usually of rather wide pore size
      distribution. Recently a novel theory of size exclusion chromatography was
      introduced to model the effect of pore size distribution. The molecular theory of
      chromatography allows taking into account the kinetics of the pore ingress and
      egress processes, the heterogeneity of the pore sizes and polymer polydispersity
      as well. The novel model was applied to inverse size exclusion chromatography
      data. In this study, we have determined the actual pore size distribution of a
      number of HPLC stationary phases. Our results agree well with the results
      obtained with the model introduced by Knox and Scott. 

PMID- 24666938
TI  - Exploring drug-protein interactions using the relationship between injection
      volume and capacity factor.
AB  - Affinity chromatography is the most widespread and widely accepted methodology
      for exploring drug-protein and protein-protein interactions. Despite the
      successful application of frontal analysis and zonal elution in affinity
      chromatography, research into the creation of new mathematical tools for data
      processing is encouraged due to these two methods' drawbacks of long analysis
      times and high ligand consumption. In this work, we created a novel mathematical
      model using the relationship between the molar amount of an injected solute and
      its capacity factor. We validated the method by analyzing the binding of drugs to
      human serum albumin (HSA) and beta2-adrenoceptor (beta2-AR). The association
      constants of omeprazole, propranolol and promethazine binding to HSA were
      determined to be (4.10+/-0.24)*10(4), (2.30+/-0.12)*10(4) and (1.24+/
      0.14)*10(4)M(-1), respectively. These constants agreed with previously reported
      literature results of 4.60*10(4), 2.30*10(4) and 1.40*10(4)M(-1). Salbutamol,
      norepinephrine, isoprenaline, bamethane and methoxyphenamine were found to bind
      to beta2-AR with association constants of (1.11+/-0.06)*10(3), (0.95+/
      0.03)*10(3), (1.66+/-0.12)*10(3), (0.47+/-0.04)*10(3) and (0.43+/-0.02)*10(3)M(
      1), respectively, which positively correlated to the negative logarithm of the
      dissociation constants obtained via radio-ligand binding assays. The proposed
      model is relatively fast and conserves ligand, and it has the potential to serve
      as an alternative method for rapidly revealing drug-protein and protein-protein
      interactions. 

PMID- 24666940
TI  - Effect of pressure on the selectivity of polymeric C18 and C30 stationary phases
      in reversed-phase liquid chromatography. Increased separation of isomeric fatty
      acid methyl esters, triacylglycerols, and tocopherols at high pressure.
AB  - A high-density, polymeric C18 stationary phase (Inertsil ODS-P) or a polymeric
      C30 phase (Inertsil C30) provided improved resolution of the isomeric fatty acids
      (FAs), FA methyl esters (FAMEs), triacylglycerols (TAGs), and tocopherols with an
      increase in pressure of 20-70MPa in reversed-phase HPLC. With respect to isomeric
      C18 FAMEs with one cis-double bond, ODS-P phase was effective for recognizing the
      position of a double bond among petroselinic (methyl 6Z-octadecenoate), oleic
      (methyl 9Z-octadecenoate), and cis-vaccenic (methyl 11Z-octadecenoate),
      especially at high pressure, but the differentiation between oleic and cis
      vaccenic was not achieved by C30 phase regardless of the pressure. A monomeric
      C18 phase (InertSustain C18) was not effective for recognizing the position of
      the double bond in monounsaturated FAME, while the separation of cis- and trans
      isomers was achieved by any of the stationary phases. The ODS-P and C30 phases
      provided increased separation for TAGs and beta- and gamma-tocopherols at high
      pressure. The transfer of FA, FAME, or TAG molecules from the mobile phase to the
      ODS-P stationary phase was accompanied by large volume reduction (-30~-90mL/mol)
      resulting in a large increase in retention (up to 100% for an increase of 50MPa)
      and improved isomer separation at high pressure. For some isomer pairs, the ODS-P
      and C30 provided the opposite elution order, and in each case higher pressure
      improved the separation. The two stationary phases showed selectivity for the
      isomers having rigid structures, but only the ODS-P was effective for
      differentiating the position of a double bond in monounsaturated FAMEs. The
      results indicate that the improved isomer separation was provided by the
      increased dispersion interactions between the solute and the binding site of the
      stationary phase at high pressure. 

PMID- 24666939
TI  - A new method for immediate derivatization of hydroxyl groups by fluoroalkyl
      chloroformates and its application for the determination of sterols and
      tocopherols in human serum and amniotic fluid by gas chromatography-mass
      spectrometry.
AB  - A new method has been described for efficient derivatization of secondary
      alicyclic hydroxyl groups in steroids by alkyl chloroformates (RCFs).
      Cholesterol, an essential human sterol and a steroid precursor in eukaryotic
      cells, was used as a model for treatment with various RCFs in an aqueous and non
      aqueous environment. While the cholesterol hydroxyl group did not react
      completely with any of the tested RCFs reagents in the former case,
      trifluoroethyl chloroformate (TFECF) or heptafluorobutyl chloroformate (HFBCF)
      fully converts cholesterol and related metabolites into the corresponding mixed
      carbonates under anhydrous conditions in seconds. The acylation reaction was
      combined with liquid-liquid microextraction (LLME) between isooctane and
      acetonitrile phase. The sample preparation requires just a stepwise addition of
      50MUl isooctane with 5MUl of a pyridine catalyst, 100MUl acetonitrile and 100MUl
      isooctane with dissolved 5MUl of the fluoroalkyl chloroformate reagent to a dried
      sample. The protocol developed in this study was successfully tested for GC-MS
      analysis of 12 important model steroids and four main tocopherols. Each analyte
      provided a single peak with excellent GC separation properties, well defined EI
      spectra containing diagnostic fragment ions suitable for their identification and
      quantitation. The new method was further validated for the determination of six
      diagnostic non-cholesterol sterols and four main tocopherols in human serum and
      in amniotic fluid. Satisfactory data were obtained in terms of calibration,
      quantitation limits (for sterols and tocopherols, 0.05 and 0.15MUg/ml,
      respectively), within-run precision (0.9-19.5%) and between-run precision (0.2
      19.0%), accuracy (82-115%) and recovery (90-110%). The validated method was
      successfully applied to GC-MS analysis of the analytes in woman sera and amniotic
      fluids and the results are well-comparable with those reported by other authors.
      The presented work demonstrates for the first time capability of the RCFs to
      derivatize alicyclic hydroxyls in steroids and tocopherols metabolites for GC-MS
      with excellent reaction rates, highest reaction yields, minor reagent consumption
      and easy conjunction with LLME methods. 

PMID- 24666942
TI  - Selection method of quasi-continuous wavelength combination with applications to
      the near-infrared spectroscopic analysis of soil organic matter.
AB  - Equidistant combination multiple linear regression (EC-MLR) for the quasi
      continuous wavelength selection of spectroscopic analysis was proposed and
      successfully applied to the reagent-free determination of soil organic matter
      with near-infrared spectroscopy. For comparison, the continuous-mode moving
      window partial least squares (MWPLS) and the discrete-mode successive projections
      algorithm (SPA) were improved by considering the stability and applied to the
      same analysis object as well. All methods exhibited good effect, but the modeling
      accuracy, stability, and validation effect of EC-MLR were better than that of the
      other two methods. Compared with MWPLS, the optimal EC-MLR model contained only
      16 wavelengths, and method complexity was substantially reduced. Compared with
      SPA-MLR, the optimal EC-MLR model could easily undergo spectral preprocessing to
      improve predictive capability. Moreover, appropriate equidistant discrete
      wavelength combination with EC-MLR corresponded to the spectral absorption band
      with proper resolution and can effectively overcome co-linearity interruption for
      the MLR model. Thus, the EC-MLR method has great potential in practical
      application and instrument design. 

PMID- 24666941
TI  - Double impact of cigarette smoke and mechanical ventilation on the alveolar
      epithelial type II cell.
AB  - INTRODUCTION: Ventilator-induced lung injury (VILI) impacts clinical outcomes in
      acute respiratory distress syndrome (ARDS), which is characterized by neutrophil
      mediated inflammation and loss of alveolar barrier function. Recent
      epidemiological studies suggest that smoking may be a risk factor for the
      development of ARDS. Because alveolar type II cells are central to maintaining
      the alveolar epithelial barrier during oxidative stress, mediated in part by
      neutrophilic inflammation and mechanical ventilation, we hypothesized that
      exposure to cigarette smoke and mechanical strain have interactive effects
      leading to the activation of and damage to alveolar type II cells. METHODS: To
      determine if cigarette smoke increases susceptibility to VILI in vivo, a
      clinically relevant rat model was established. Rats were exposed to three
      research cigarettes per day for two weeks. After this period, some rats were
      mechanically ventilated for 4 hours. Bronchoalveolar lavage (BAL) and
      differential cell count was done and alveolar type II cells were isolated.
      Proteomic analysis was performed on the isolated alveolar type II cells to
      discover alterations in cellular pathways at the protein level that might
      contribute to injury. Effects on levels of proteins in pathways associated with
      innate immunity, oxidative stress and apoptosis were evaluated in alveolar type
      II cell lysates by enzyme-linked immunosorbent assay. Statistical comparisons
      were performed by t-tests, and the results were corrected for multiple
      comparisons using the false discovery rate. RESULTS: Tobacco smoke exposure
      increased airspace neutrophil influx in response to mechanical ventilation. The
      combined exposure to cigarette smoke and mechanical ventilation significantly
      increased BAL neutrophil count and protein content. Neutrophils were
      significantly higher after smoke exposure and ventilation than after ventilation
      alone. DNA fragments were significantly elevated in alveolar type II cells. Smoke
      exposure did not significantly alter other protein-level markers of cell
      activation, including Toll-like receptor 4; caspases 3, 8 and 9; and heat shock
      protein 70. CONCLUSIONS: Cigarette smoke exposure may impact ventilator
      associated alveolar epithelial injury by augmenting neutrophil influx. We found
      that cigarette smoke had less effect on other pathways previously associated with
      VILI, including innate immunity, oxidative stress and apoptosis.

PMID- 24666943
TI  - Atomization of cadmium compounds under reactive and inert high-temperature
      environment with stationary sample introduction.
AB  - Atomization of cadmium compounds (acetate, chloride, nitrate, perchlorate,
      sulfate, formate, propionate) was studied using flame atomic absorption
      spectrometry. Our goal was to study processes influencing atomization separately,
      the focus was on the contribution of thermal properties of substances to
      atomization. For this purpose new techniques and equipment have been developed,
      such as a special separated three-slot burner, quartz flame furnace, and an
      electrically heated thermospectrometer. According to quartz flame furnace and
      thermospectrometric measurements, cadmium salts do not atomize below 600  degrees
      C in an inert atmosphere. We found that in the thermospectrometer the atomization
      of cadmium compounds follows at least two different reaction courses. At lower
      temperatures (650-700  degrees C) a slower mechanism is dominant at higher
      regions of the furnace, while at 800  degrees C a faster mechanism demanding less
      residence time in the furnace becomes dominant. Under inert atmosphere the degree
      of atomization strongly depends on the thermal properties of substances. 

PMID- 24666944
TI  - Nuclear magnetic resonance spectra and (207)Pb chemical-shift tensors of lead
      carboxylates relevant to soap formation in oil paintings.
AB  - Soap formation in traditional oil paintings occurs when heavy-metal-containing
      pigments, such as lead white, 2PbCO3.Pb(OH)2, and lead tin yellow type I,
      Pb2SnO4, react with fatty acids in the binding medium. These soaps may form
      aggregates that can be 100-200 MUm in diameter, which swell and protrude through
      the paint surface, resulting in the degradation of the paint film and damage to
      the integrity of the artwork. The factors that trigger soap formation and the
      mechanism(s) of the process are not yet well understood. To elucidate these
      issues, chemical and structural information is necessary, which can be obtained
      using solid-state (207)Pb and (13)C nuclear magnetic resonance (NMR). In this
      article, we report (207)Pb and (13)C solid-state NMR spectra and (207)Pb chemical
      shift tensors of lead carboxylates implicated in soap formation: lead stearate,
      lead palmitate, and lead azelate, in addition to lead oleate and lead heptanoate
      for comparison. The (13)C cross polarization with magic-angle spinning (MAS)
      spectra of these lead carboxylates show resonance doubling for the carbons
      closest to the lead, indicating two different conformations of the fatty acid
      chains in the asymmetric unit. The (207)Pb NMR spectra, from which tensors were
      determined, were obtained with direct excitation and spin-temperature
      alternation, with and without MAS, and with the wide band uniform rate smooth
      truncation Carr-Purcell-Meiboom-Gill pulse sequence. The results of these
      experiments show that the local coordination environment of lead azelate is
      different from lead palmitate and lead stearate and could thus be distinguished
      from these in a paint film displaying soap formation. In addition, comparing the
      (207)Pb NMR chemical-shift tensors of the lead carboxylates studied shows that
      crystal packing of the acyl chains may be a factor in determining the
      coordination environment around the lead. 

PMID- 24666945
TI  - Surface-enhanced Raman scattering detection of ammonium nitrate samples
      fabricated using drop-on-demand inkjet technology.
AB  - The United States Army and the first responder community are increasingly
      focusing efforts on energetic materials detection and identification. Main
      hazards encountered in theater include homemade explosives and improvised
      explosive devices, in part fabricated from simple components like ammonium
      nitrate (AN). In order to accurately detect and identify these unknowns
      (energetic or benign), fielded detection systems must be accurately trained using
      well-understood universal testing substrates. These training substrates must
      contain target species at known concentrations and recognized polymorphic phases.
      Ammonium nitrate is an explosive precursor material that demonstrates several
      different polymorphic phases dependent upon how the material is deposited onto
      testing substrates. In this paper, known concentrations of AN were uniformly
      deposited onto commercially available surface-enhanced Raman scattering (SERS)
      substrates using a drop-on-demand inkjet printing system. The phase changes
      observed after the deposition of AN under several solvent conditions are
      investigated. Characteristics of the collected SERS spectra of AN are discussed,
      and it is demonstrated that an understanding of the exact nature of the AN
      samples deposited will result in an increased ability to accurately and reliably
      "train" hazard detection systems. 

PMID- 24666946
TI  - Determination of antimony by surface-enhanced Raman spectroscopy.
AB  - A highly sensitive method for the detection and quantitative evaluation of
      antimony(III) using the surface-enhanced Raman scattering (SERS) technique is
      demonstrated. The method is based on the analysis of SERS spectra intensity of
      antimony bound to phenylfluorone (Sb-PhF). Phenylfluorone is widely used as an
      organic reagent for the spectrophotometric determination of some heavy metals.
      For the SERS experiment a Sb-PhF complex was adsorbed onto the silvered porous
      silicon substrate. The significant degradation of the SERS signal was observed
      during measurements in the air. The time evolution of SERS spectra at ambient and
      degassed conditions was investigated to find an optimal regime for SERS
      measurements. The limit of Sb detection in degassed samples was determined to be
      near 1 ng/mL, which is one order of magnitude less than that attainable by the
      photometric approach. The linear range of the method to Sb(III) was found to a
      mass concentration range of 1-10 ng/mL. This approach permits an absolute
      quantity of Sb(III) to be detected at the picogram level (~50 pg). It is
      remarkable that a very small sample volume (50 MUL) is required for SERS
      analysis. Moreover this technique offers high selectivity owing to the
      distinctive vibrational features for the metallorganic complex and to the
      resonance character of Raman spectra. The proposed SERS-based detection of Sb is
      a fast and highly sensitive method for use in environmental and industrial waste
      monitoring as well as for forensic science to determine gunshot residue. We
      expect that the approach reported herein can be further extended to develop new
      detection techniques for other heavy metals. 

PMID- 24666947
TI  - Interactions between the antifungal drug myclobutanil and gold and silver
      nanoparticles in Penicillium digitatum investigated by surface-enhanced Raman
      scattering.
AB  - Surface-enhanced Raman scattering (SERS) of an antifungal reagent, myclobutanil
      (MCB), was performed on Au and Ag nanoparticles (NPs) to estimate the drug
      release behaviors in fungal cells. A density functional theory (DFT) calculation
      was introduced to predict a favorable binding site of MCB to either the Ag or Au
      atom. Myclobutanil was presumed to bind more strongly to Au than to Ag in their
      most stable, optimized geometries of the N4 atom in its 1,2,4-triazole unit
      binding to the metal atom. Strong intensities were observed in the Ag SERS
      spectra only at acidic pH values, whereas the most prominent peaks in the Au SERS
      spectra of MCB matched quite well with those of 1,2,4-triazole regardless of pH
      conditions. The Raman spectral intensities of the MCB-assembled Ag and Au NPs
      decreased after treatment with either potato dextrose agar (PDA) or glutathione
      (GSH). Darkfield microscopy and confocal SERS were performed to analyze the MCB
      assembled metal NPs inside Penicillium digitatum fungal cells. The results
      suggested that MCB was released from the metal NPs in the intracellular GSH in
      the fungi because we observed only fungal cell peaks. 

PMID- 24666948
TI  - Long-pulsed luminescence for the measurement of dissolved oxygen.
AB  - Thin-film luminescent sensors were used to measure dissolved oxygen in picoliter
      volumes for the purpose of monitoring single-cell oxygen consumption rates, and
      that work served as the motivation for the development of the method described
      here. A few different platinum porphyrin sensor materials were examined, with all
      measurements conducted microscopically. By employing convolution theory to
      understand observed responses, including an unexpected red luminescent emission
      from an optic, we developed a new, rapid method for the determination of
      exponential decay lifetime. This new method of long-pulsed luminescence offers
      substantially improved signal-to-noise ratios for detected signals as long as
      self-illumination sources are carefully controlled in the experimental set-up. 

PMID- 24666949
TI  - High-pressure-low-temperature cryostat designed for use with fourier transform
      infrared spectrometers and time-resolved infrared spectroscopy.
AB  - The design for a new high-pressure-low-temperature infrared (IR) cell for
      performing experiments using conventional Fourier transform infrared or fast
      laser-based time-resolved infrared spectroscopy, in a range of solvents, is
      described. The design builds upon a commercially available compressor and cold
      end (Polycold PCC((r)) and CryoTiger((r))), which enables almost vibration-free
      operation, ideal for use with sensitive instrumentation. The design of our cell
      and cryostat allows for the study of systems at temperatures from 77 to 310 K and
      at pressures up to 250 bar. The CaF2 windows pass light from the mid-IR to the
      ultraviolet (UV), enabling a number of experiments to be performed, such as
      Raman, UV-visible absorption spectroscopy, and time-resolved techniques where
      sample excitation/probing using continuous wave or pulsed lasers is required. We
      demonstrate the capabilities of this cell by detailing two different
      applications: (i) the reactivity of a range of Group V-VII organometallic alkane
      complexes using time-resolved spectroscopy on the millisecond timescale and (ii)
      the gas-to-liquid phase transition of CO2 at low temperature, which is applicable
      to measurements associated with transportation issues related to carbon capture
      and storage. 

PMID- 24666950
TI  - Near-infrared spectral image analysis of pork marbling based on Gabor filter and
      wide line detector techniques.
AB  - Marbling is an important quality attribute of pork. Detection of pork marbling
      usually involves subjective scoring, which raises the efficiency costs to the
      processor. In this study, the ability to predict pork marbling using near
      infrared (NIR) hyperspectral imaging (900-1700 nm) and the proper image
      processing techniques were studied. Near-infrared images were collected from pork
      after marbling evaluation according to current standard chart from the National
      Pork Producers Council. Image analysis techniques-Gabor filter, wide line
      detector, and spectral averaging-were applied to extract texture, line, and
      spectral features, respectively, from NIR images of pork. Samples were grouped
      into calibration and validation sets. Wavelength selection was performed on
      calibration set by stepwise regression procedure. Prediction models of pork
      marbling scores were built using multiple linear regressions based on derivatives
      of mean spectra and line features at key wavelengths. The results showed that the
      derivatives of both texture and spectral features produced good results, with
      correlation coefficients of validation of 0.90 and 0.86, respectively, using
      wavelengths of 961, 1186, and 1220 nm. The results revealed the great potential
      of the Gabor filter for analyzing NIR images of pork for the effective and
      efficient objective evaluation of pork marbling. 

PMID- 24666951
TI  - Photothermal response of near-infrared-absorbing NanoGUMBOS.
AB  - The photothermal properties of several near-infrared-absorbing nanoparticles
      derived from group of uniform materials based on organic salts (GUMBOS) and
      composed of cationic dyes coupled with biocompatible anions are evaluated. These
      nanoparticles were synthesized using a reprecipitation method performed at
      various pH values: 2.0, 5.0, 7.0, 9.0, and 11.0. The cations for the
      nanoparticles derived from GUMBOS (nanoGUMBOS), [1048] and [1061], have
      absorbance maxima at wavelengths overlapping with human soft tissue absorbance
      minima. Near-infrared-absorbing nanoGUMBOS excited with a 1064 nm continuous
      laser led to heat generation, with an average temperature increase of 20.4 +/-
      2.7  degrees C. Although the [1061][Deoxycholate] nanoGUMBOS generated the
      highest temperature increase (23.7 +/- 2.4  degrees C), it was the least
      photothermally efficient compound (13.0%) due to its relatively large energy band
      gap of 0.892 eV. The more photothermally efficient compound [1048][Ascorbate]
      (64.4%) had a smaller energy band gap of 0.861 eV and provided an average
      photothermal temperature increase of 21.0 +/- 2.1  degrees C. 

PMID- 24666952
TI  - New design method for a phase plate in super-resolution fluorescence microscopy.
AB  - The performance of a super-resolution fluorescence depletion microscope system
      depends crucially on the precise alignment of the pump and erase beams with the
      axis of the focusing objective. Here, we propose a new design method for a two
      color spiral phase plate with a single-layer structure (S2SPP), and we
      experimentally investigate the image properties given by the phase plate. In
      spite of its simple structure, the plate can provide a super-resolution image
      with a spatial resolution better than 70 nm. Beside eliminating alignment
      problems and yielding a compact setup, the simplicity of fabrication of the S2SPP
      makes our proposed method very suitable for commercial microscope systems. 

PMID- 24666954
TI  - Carbon swan spectra measurements following breakdown of nitro compound explosive
      simulants.
AB  - Our measurements of micro-plasma following laser-induced optical breakdown of
      nitro compound explosive simulants, here 3-nitrobenzoic acid, show well-developed
      molecular spectra during the first several hundreds of nanoseconds. Analysis of
      recorded carbon spectra is accomplished using accurate line strengths for the
      diatomic molecular Swan system. Presence of hydrogen-beta allows us to infer
      electron density in the plasma evolution. Computational challenges include
      accounting for background variation and appropriate modeling of hydrogen embedded
      in molecular spectra. Recorded and computed spectra agree nicely for time delays
      on the order of 1.6 MUs from optical breakdown when using a single temperature
      for local thermodynamic equilibrium plasma. 

PMID- 24666953
TI  - Aluminum flame temperature measurements in solid propellant combustion.
AB  - The temperature in an aluminized propellant is determined as a function of height
      and plume depth from diatomic AlO and thermal emission spectra. Higher in the
      plume, 305 and 508 mm from the burning surface, measured AlO emission spectra
      show an average temperature with 1sigma errors of 2980 +/- 80 K. Lower in the
      plume, 152 mm from the burning surface, an average AlO emission temperature of
      2450 +/- 100 K is inferred. The thermal emission analysis yields higher
      temperatures when using constant emissivity. Particle size effects along the
      plume are investigated using wavelength-dependent emissivity models. 

PMID- 24666955
TI  - Thermal behavior of poly(lactic acid)-nanocomposite studied by near-infrared
      imaging based on roundtrip temperature scan.
AB  - The thermal behavior of poly(lactic acid) (PLA) was studied by near-infrared
      imaging to provide a molecular-level understanding of the physical improvement
      caused by nanoclay dispersion. A set of PLA samples, each having different
      nanoclay dispersion, was prepared under varying sonication time. Crystallinity
      variation of the polymer interacting with the nanoclay particles was analyzed by
      a roundtrip temperature scan below the melting temperature. Namely, the samples
      underwent heating and then cooling in the opposite way during the spectral
      measurement. The discrepancy of the spectral feature between the heating and the
      cooling indicated the development of the hysteresis associated with the cold
      crystallization of the PLA lamellae. The generation of the spectral residuals
      revealed the inner working mechanism of how the polymer structure undergoes
      variation depending on the presence of the clay particles and their dispersions.
      The sonication brings substantial dispersion of the nanoclay over the polymer
      matrix. The nanoclay particles then induce the additional development of the
      crystalline structure due to the molecular interaction between the PLA and
      nanoclay arising from the presence of enormous surface area, which in turn
      induces variation of mechanical strength to the polymer. 

PMID- 24666956
TI  - First direct body fat content measurement during pregnancy using Fourier
      transform near-infrared spectroscopy.
AB  - Currently, there are no direct and reliable methods to measure the body fat
      content of women during pregnancy. Estimates of fat accretion can significantly
      affect calculations of energy requirements. We report here the first direct
      measurement of determining the body fat content of two women during pregnancy
      using the Fourier transform near-infrared spectroscopy (FT-NIR) method. Fourier
      transform near-infrared spectroscopy was shown to provide comparable results to
      dual-energy X-ray absorptiometry and magnetic resonance imaging. These latter
      methods, even though very reliable to measure body fat levels, cannot be used to
      measure the body fat of women during pregnancy because of health concerns, while
      FT-NIR poses no health risk. The FT-NIR results showed the percent body fat
      remained relatively constant throughout pregnancy, but fat mass and fat free mass
      increased. Fat mass followed an S curve with a maximum increase between 15 to 25
      weeks of gestation that was only detected by repeated measurements using the FT
      NIR technique. These results demonstrate the value of the FT-NIR method to
      directly measure the fat content of pregnant women in minutes instead of relying
      on indirect calculations or taking measurements before and after pregnancy to
      track gestational fat mass accretion. 

PMID- 24666957
TI  - Variation in the transmission near-infrared signal with depth in turbid media.
AB  - Transmission near-infrared (NIR) measurements of a 1 mm thick aspirin disk were
      made at different positions as it was moved through a stack of eight 0.5 mm thick
      disks of microcrystalline cellulose (Avicel). The magnitude of the first
      derivative of absorbance for the aspirin interlayer at 8934 cm(-1) was lower when
      the disk was placed at the top or bottom of the stack of Avicel disks, with the
      largest signal observed when the aspirin was positioned at the central positions.
      The variation in signal with depth is consistent with that observed previously
      for transmission Raman spectrometry. In both cases, the trend observed can be
      attributed to lower photon density at the air-sample interface, relative to the
      center of the sample, owing to loss of photons to the air. This results in a
      reduction in the number of photons absorbed or Raman photons generated and
      subsequently detected when the interlayer occupies a near-surface position. 

PMID- 24666958
TI  - A reproducible automated segmentation algorithm for corneal epithelium cell
      images from in vivo laser scanning confocal microscopy.
AB  - PURPOSE: To evaluate an automated process to find borders of corneal basal
      epithelial cells in pictures obtained from in vivo laser scanning confocal
      microscopy (Heidelberg Retina Tomograph III with Rostock corneal module).
      METHODS: On a sample of 20 normal corneal epithelial pictures, images were
      segmented through an automated four-step segmentation algorithm. Steps of the
      algorithm included noise reduction through a fast Fourier transform (FFT) band
      pass filter, image binarization with a mean value threshold, watershed
      segmentation algorithm on distance map to separate fused cells and Voronoi
      diagram segmentation algorithm (which gives a final mask of cell borders). Cells
      were then automatically counted using this border mask. On the original image
      either with contrast enhancement or noise reduction, cells were manually counted
      by a trained operator. RESULTS: The average cell density was 7722.5 cells/mm(2)
      as assessed by automated analysis and 7732.5 cells/mm(2) as assessed by manual
      analysis (p = 0.93). Correlation between automated and manual analysis was strong
      (r = 0.974 [0.934-0.990], p < 0.001). Bland-Altman method gives a mean difference
      in density of 10 cells/mm(2) and a limits of agreement ranging from -971 to +991
      cells/mm(2) . Visually, the algorithm correctly found almost all borders.
      CONCLUSION: This automated segmentation algorithm is worth for assessing corneal
      epithelial basal cell density and morphometry. This procedure is fully
      reproducible, with no operator-induced variability.

PMID- 24666959
TI  - Obesity and perioperative acute kidney injury: a focused review.
AB  - Obesity has reached epidemic proportions in the developed world today. Obesity is
      a significant risk factor for cardiovascular disease, hypertension, diabetes
      mellitus, and chronic kidney disease. There has been renewed interest in the role
      of perioperative renal dysfunction with the establishment of new diagnostic
      criteria for kidney dysfunction such as the Acute Kidney Injury Network criteria
      and the Risk-Injury-Failure-Loss End-stage kidney disease criteria. There is
      increasing evidence pointing to the role of visceral adipose tissue and
      adipokines in the pathophysiology of obesity. Furthermore, the traditional
      methods of quantifying obesity such as body mass index are increasing being
      questioned because they may not accurately reflect true visceral obesity and may
      skew epidemiologic classification of metabolically healthy patients. Recent
      epidemiologic studies suggest the existence of an obesity paradox wherein obese
      patients seem to have superior perioperative outcomes compared with patients with
      normal and low body mass index. We seek to review the epidemiologic and
      pathophysiologic aspects of obesity, especially with respect to structural and
      functional changes in kidney function and their impact on perioperative outcomes.

PMID- 24666960
TI  - Cycling-off criteria during pressure support ventilation: what do we have to
      monitor?

PMID- 24666961
TI  - Influence of abdominal obesity on multiorgan dysfunction and mortality in acute
      respiratory distress syndrome patients treated with prone positioning.
AB  - PURPOSE: Obesity is a worldwide pandemic, and obese patients face an increased
      risk of developing acute respiratory distress syndrome (ARDS). Prone positioning
      (PP) is a frequently used intervention in the treatment of ARDS. There are no
      data describing the impact of PP on morbidity and mortality in abdominally obese
      patients. We report our observations in abdominally obese ARDS patients treated
      with PP. MATERIALS AND METHODS: Patients with ARDS (n=82) were retrospectively
      divided into 2 groups characterized by presence (n=41) or absence (n=41) of
      abdominal obesity as defined by a sagittal abdominal diameter of 26 cm or more.
      RESULTS: There was no difference in cumulative time abdominally obese patients
      were placed in prone position from admission to day 7 (41.0 hours [interquartile
      range, 50.5 hours] vs 39.5 hours [interquartile range, 61.5 hours]; P=.65) or in
      overall intensive care unit mortality (34% vs 34%; P=1). However, abdominally
      obese patients developed renal failure (83% vs 35%; P<.001) and hypoxic hepatitis
      (22% vs 2%; P=.015) more frequently. A significant interaction effect between
      abdominal obesity and prone position with respect to mortality risk (likelihood
      ratio, P=.0004) was seen if abdominally obese patients were treated with
      prolonged cumulative PP. CONCLUSION: A cautious approach to PP should be
      considered in abdominally obese patients.

PMID- 24666962
TI  - Digital imaging approaches for phenotyping whole plant nitrogen and phosphorus
      response in Brachypodium distachyon.
AB  - This work evaluates the phenotypic response of the model grass (Brachypodium
      distachyon (L.) P. Beauv.) to nitrogen and phosphorus nutrition using a
      combination of imaging techniques and destructive harvest of shoots and roots.
      Reference line Bd21-3 was grown in pots using 11 phosphorus and 11 nitrogen
      concentrations to establish a dose-response curve. Shoot biovolume and biomass,
      root length and biomass, and tissue phosphorus and nitrogen concentrations
      increased with nutrient concentration. Shoot biovolume, estimated by imaging, was
      highly correlated with dry weight (R(2) > 0.92) and both biovolume and growth
      rate responded strongly to nutrient availability. Higher nutrient supply
      increased nodal root length more than other root types. Photochemical efficiency
      was strongly reduced by low phosphorus concentrations as early as 1 week after
      germination, suggesting that this measurement may be suitable for high throughput
      screening of phosphorus response. In contrast, nitrogen concentration had little
      effect on photochemical efficiency. Changes in biovolume over time were used to
      compare growth rates of four accessions in response to nitrogen and phosphorus
      supply. We demonstrate that a time series image-based approach coupled with
      mathematical modeling provides higher resolution of genotypic response to
      nutrient supply than traditional destructive techniques and shows promise for
      high throughput screening and determination of genomic regions associated with
      superior nutrient use efficiency.

PMID- 24666964
TI  - An in vitro model to study brain tissue recovery.
AB  - Brain tissue slices can be maintained within metabolically stable conditions for
      long periods of time (hours). This experimental setting has been productive for
      investigating long-term neural function in vitro. Here, we utilize this
      experimental approach to describe the recovery of functional connectivity in
      slices from the mouse hippocampus. Hippocampal slices were cut up bisecting the
      CA1 region (parietal cut) and each severed half placed adjacent to the other.
      Stimulation and recording electrodes were placed on each side of the cut; with
      one electrode stimulating one hemi-slice (20 V, 0.033 Hz) and the other electrode
      recording the evoked response from the adjacent hemi-slice. As expected, no
      evoked response was observed shortly after the beginning of stimulation. However,
      20-40 min after the initiation of stimulation a large depolarization signal was
      detected. Right after that, fiber volley potentials were observed in the adjacent
      hemi-slice. After 1h excitatory postsynaptic potentials (EPSP) were detected.
      Based on this observation, we hypothesize that recovery of functional
      connectivity is enhanced by constant delivery of electrical pulses at low
      frequency to the damaged neural tissue. The described in vitro slice system may
      become a very suitable experimental method to investigate strategies to enhance
      the recovery of neural connectivity after brain injury.

PMID- 24666963
TI  - The feasibility and acceptability of training volunteer mealtime assistants to
      help older acute hospital inpatients: the Southampton Mealtime Assistance Study.
AB  - AIMS AND OBJECTIVES: To determine the feasibility and acceptability of using
      trained volunteers as mealtime assistants for older hospital inpatients.
      BACKGROUND: Poor nutrition among hospitalised older patients is common in many
      countries and associated with poor outcomes. Competing time pressures on nursing
      staff may make it difficult to prioritise mealtime assistance especially on wards
      where many patients need help. DESIGN: Mixed methods evaluation of the
      introduction of trained volunteer mealtime assistants on an acute female medicine
      for older people ward in a teaching hospital in England. METHODS: A training
      programme was developed for volunteers who assisted female inpatients aged 70
      years and over on weekday lunchtimes. The feasibility of using volunteers was
      determined by the proportion recruited, trained, and their activity and retention
      over one year. The acceptability of the training and of the volunteers' role was
      obtained through interviews and focus groups with 12 volunteers, nine patients
      and 17 nursing staff. RESULTS: Fifty-nine potential volunteers were identified:
      38 attended a training session, of whom 29 delivered mealtime assistance,
      including feeding, to 3911 (76%) ward patients during the year (mean duration of
      assistance 5.5 months). The volunteers were positive about the practical aspects
      of training and ongoing support provided. They were highly valued by patients and
      ward staff and have continued to volunteer. CONCLUSIONS: Volunteers can be
      recruited and trained to help acutely unwell older female inpatients at
      mealtimes, including feeding. This assistance is sustainable and is valued.
      RELEVANCE TO CLINICAL PRACTICE: This paper describes a successful method for
      recruitment, training and retention of volunteer mealtime assistants. It includes
      a profile of those volunteers who provided the most assistance, details of the
      training programme and role of the volunteers and could be replicated by nursing
      staff in other healthcare units.

PMID- 24666965
TI  - Quantum dot cascade laser.
AB  - We demonstrated an unambiguous quantum dot cascade laser based on
      InGaAs/GaAs/InAs/InAlAs heterostructure by making use of self-assembled quantum
      dots in the Stranski-Krastanow growth mode and two-step strain compensation
      active region design. The prototype generates stimulated emission at lambda ~
      6.15 MUm and a broad electroluminescence band with full width at half maximum
      over 3 MUm. The characteristic temperature for the threshold current density
      within the temperature range of 82 to 162 K is up to 400 K. Moreover, our
      materials show the strong perpendicular mid-infrared response at about 1,900 cm
      1. These results are very promising for extending the present laser concept to
      terahertz quantum cascade laser, which would lead to room temperature operation.
      PACS: 42.55.Px; 78.55.Cr; 78.67.Hc.

PMID- 24666966
TI  - Implementation of best medical therapy for cardiovascular risk factors in
      vascular surgery patients treated in a tertiary referral regional unit.
AB  - OBJECTIVE: Current clinical evidence reports that antiplatelet, statin,
      angiotensin-converting enzyme inhibitor and beta blockade therapies have
      advantageous effects on vascular surgery patient morbidity and mortality.
      Unfortunately, such patients appear to be less likely to receive optimal medical
      management when compared with coronary artery disease patients. This study
      assessed medical therapy prescribing in patients attending a regional vascular
      surgery unit. METHODS: A retrospective review between February 2010 and February
      2011 was performed for patients undergoing aortic aneurysm, carotid, peripheral
      arterial and amputation surgeries. Gender, age, smoking history, body mass index
      and cardiovascular risk factors were documented from inpatient charts. Current
      admission medications and subsequent modification by the vascular team were
      recorded. RESULTS: Two hundred and forty-four patients (male = 165, mean age = 71
      years) were identified. Prevalence of hypertension, hypercholesterolaemia,
      myocardial infarction, angina, stroke and diabetes was higher than in the general
      population. A total of 201 (82.3%) patients were on antiplatelets or
      antithrombotics upon admission to the vascular ward, which was improved to 231
      (94.6%) patients on discharge. A total of 180 (73.7%) patients were on lipid
      lowering therapy upon admission, which was improved to 213 (87.2%) patients on
      discharge. A total of 115 (47.1%) patients were on ACE-inhibitor or angiotensin 2
      receptor blocker medications on admission and this was improved to 118 (48.3%)
      upon discharge. A total of 87 (35.6%) patients were on a beta-blocker, which was
      improved to 93 (38.1%) patients upon discharge. CONCLUSION: Despite increased
      implementation of best medical therapy in the community with compliance rates
      greater than 73% for aspirin and statin therapy, further improvement is
      warranted. Vascular surgeons should remain vigilant for further opportunities to
      optimise medical therapy in this high-risk patient group particularly with
      antithrombotic, lipid lowering and antihypertensive therapies.

PMID- 24666967
TI  - Tetralogy of Fallot with coarctation of the aorta: a newly recognised
      developmental and anatomic syndrome.
AB  - Tetralogy of Fallot and coarctation of the aorta is an exceptional association.
      We report here four cases of infants referred for tetralogy of Fallot with or
      without pulmonary atresia associated with aortic coarctation from 1974 to 2013.
      All had a right aortic arch, and the coarctation was abnormally situated between
      the right common carotid and the right subclavian arteries. In all, two infants
      had an abnormal left subclavian artery and one child had DiGeorge syndrome. All
      underwent staged surgical repair of the left and right-sided obstructions. A
      review of the literature shows two types of coarctation in this context. In left
      aortic arch, coarctation is situated distal to the left subclavian artery. In
      right aortic arch, coarctation is distal to the right common carotid artery,
      mirror-image of interrupted left aortic arch type B, associated with anomalies of
      the branches of the aorta, and should be considered a complex anomaly of aortic
      arches in the setting of an outflow tract defect due to abnormal migration of
      cardiac neural crest cells. Screening for this unusual association is critical in
      the initial assessment of all patients with tetralogy of Fallot. 

PMID- 24666968
TI  - Multilocus microsatellite typing reveals a genetic relationship but, also,
      genetic differences between Indian strains of Leishmania tropica causing
      cutaneous leishmaniasis and those causing visceral leishmaniasis.
AB  - BACKGROUND: Leishmaniases are divided into cutaneous (CL) and visceral
      leishmaniasis (VL). In the Old World, CL is caused by Leishmania (L.) major, L.
      tropica and L. aethiopica. L. tropica can also visceralize and cause VL. In
      India, the large epidemics of VL are caused by L. donovani and cases of CL are
      caused by L. major and L. tropica. However, strains of L. tropica have also been
      isolated from Indian cases of VL.This study was done to see if Indian strains of
      L. tropica isolated from human cases of CL are genetically identical to or
      different from Indian strains of L. tropica isolated from human cases of VL and
      to see if any genetic differences found correlated with clinical outcome
      presenting as either CL or VL. METHODS: Multilocus microsatellite typing (MLMT),
      employing 12 independent genetic markers specific to L. tropica, was used to
      characterize and identify eight strains of L. tropica isolated from human cases
      of CL examined in clinics in Bikaner City, Rajasthan State, north-west India.
      Their microsatellite profiles were compared to those of 156 previously typed
      strains of L. tropica from various geographical locations that were isolated from
      human cases of CL and VL, hyraxes and sand fly vectors. RESULTS: Bayesian,
      distance-based and factorial correspondence analyses revealed two confirmed
      populations: India/Asia and Israel/Palestine that subdivided, respectively, into
      two and three subpopulations. A third population, Africa/Galilee, as proposed by
      Bayesian analysis was not supported by the other applied methods. The strains of
      L. tropica from Bikaner isolated from human cases of CL fell into one of the
      subpopulations in the population India/Asia together with strains from other
      Asian foci. Indian strains isolated from human cases of VL fell into the same sub
      population but were not genetically identical to the Bikaner strains of L.
      tropica. CONCLUSIONS: It seems that the genetic diversity encountered between the
      two groups of Indian strains is mainly owing to their geographical origins rather
      than their different times of isolation. Also, the genetic differences seen
      between the dermatotropic and viscerotropic strains might be connected with the
      difference in pathogenicity.

PMID- 24666969
TI  - The involvement of AMPK/GSK3-beta signals in the control of metastasis and
      proliferation in hepato-carcinoma cells treated with anthocyanins extracted from
      Korea wild berry Meoru.
AB  - BACKGROUND: Activation of the Wnt pathway is known to promote tumorigenesis and
      tumor metastasis, and targeting Wnt pathway inhibition has emerged as an
      attractive approach for controlling tumor invasion and metastasis. The major
      pathway for inhibiting Wnt is through the degradation of beta-catenin by the GSK3
      beta/CK1/Axin/APC complex. It was found that Hep3B hepato-carcinoma cells respond
      to anthocyanins through GSK3-beta-induced suppression of beta-catenin; however,
      they cannot dephosphorylate GSK3-beta without AMPK activation. METHODS: We tested
      the effects of anthocyanins on proliferation and apoptosis by MTT and Annexin V
      PI staining in vitro. Mouse xenograft models of hepato-carcinomas were
      established by inoculation with Hep3B cells, and mice were injected with 50
      mg/kg/ml of anthocyanins. In addition, protein levels of p-GSK3-beta, beta
      catenin, p-AMPK, MMP-9, VEGF, and Ang-1 were also analyzed using western blot.
      RESULTS: Anthocyanins decrease phospho-GSK3-beta and beta-catenin expression in
      an in vivo tumor xenograft model, increase AMPK activity in this model, and
      inhibit cell migration and invasion, possibly by inhibiting MMP-2 (in vitro) and
      the panendothelial marker, CD31 (in vivo). To elucidate the role of the GSK3
      beta/beta-catenin pathway in cancer control, we conditionally inactivated this
      pathway, using activated AMPK for inhibition. Further, we showed that AMPK siRNA
      treatment abrogated the ability of anthocyanins to control cell proliferation and
      metastatic potential, and Compound C, an AMPK inhibitor, could not restore GSK3
      beta regulation, as exhibited by anthocyanins in Hep3B cells. CONCLUSION: These
      observations imply that the AMPK-mediated GSK3-beta/beta-catenin circuit plays
      crucial roles in inhibiting cancer cell proliferation and metastasis in
      anthocyanin-treated hepato-carcinoma cells of Meoru origin.

PMID- 24666970
TI  - Kinetics of pulmonary immune cells, antibody responses and their correlations
      with the viral clearance of influenza A fatal infection in mice.
AB  - Fatal influenza A virus infection is a major threat to public health throughout
      the world. Lung macrophages and neutrophils have critical roles for both the
      pathogenesis and viral clearance of fatal viral infections. These are complicated
      by the interaction of innate immunity and adaptive immunity against viral
      infection. In this study, we investigated the overall kinetics of lung
      macrophages, neutrophils, CD4+T cells, CD8+T cells, CD38+ cells, and CD138+
      cells, the levels of antibody and cytokine responses, both in the early and late
      phases of fatal infection with A/PR/8/34 (H1N1) virus in mice. The changes in
      lung viral load were also evaluated. We found that pulmonary macrophages and
      neutrophils both accumulated in the early and late phases of fatal infections and
      they positively correlated with the lung and serum antibody titers, and
      negatively correlated with the viral load locally. The secretion of IL-6 might
      relate to high numbers of macrophages and neutrophils in the early infection. The
      work implies that pulmonary macrophages, neutrophils and the antibody response
      all have an essential role in virus elimination of fatal influenza A viral
      infection. These findings may have implications for the development of
      prophylactic and therapeutic strategies in fatal influenza A viral infection.
      Further evaluation of the cooperation among macrophages, neutrophils and antibody
      responses in eliminating the virus with fatal infection is needed.

PMID- 24666972
TI  - Relationship of the recurrent laryngeal nerve to the superior parathyroid gland
      during thyroidectomy.
AB  - Design: The relationship of the recurrent laryngeal nerve to the superior
      parathyroid gland during consecutive thyroidectomies was prospectively evaluated.
      When one structure was noted, careful dissection was performed to locate the
      other structure, to preserve their natural anatomical relationship. Patients: In
      total, 103 consecutive thyroid lobectomies were performed on 73 patients. The
      distance from the superior parathyroid gland to the recurrent laryngeal nerve was
      recorded. Results: In 88 cases (88.9 per cent), the superior parathyroid gland
      was identified within 5 mm of the recurrent laryngeal nerve. In 62 cases (62.6
      per cent), the gland was within 1 mm of the recurrent laryngeal nerve. The height
      of the thyroid lobe was positively associated with the distance between the two
      structures (p = 0.001), as was the incidence of cancer (p = 0.033). The incidence
      of recurrent laryngeal nerve paresis was less than 4 per cent. Conclusion: In
      most cases, the recurrent laryngeal nerve was found in close proximity to the
      superior parathyroid gland. In a thyroid gland with a large height, or in a
      cancerous lobe, this relationship is less reliable.

PMID- 24666971
TI  - Aldosterone to active renin ratio is associated with nocturnal blood pressure in
      obese and treated hypertensive patients: the Styrian Hypertension Study.
AB  - High aldosterone levels are considered to play a key role in arterial
      hypertension. Data on the relationship between the aldosterone to active renin
      ratio (AARR), a quantity of aldosterone excess, and ambulatory blood pressure
      (BP) monitoring (ABPM) during the night are, however, sparse. Hypertensive
      patients were recruited from local outpatient clinics who underwent 24-hour urine
      collection and in parallel ABPM. Plasma aldosterone and renin concentrations were
      measured by radioimmunoassay. A total of 211 patients (age, 60.2+/-10.2 years;
      51.9% female) with a mean systolic/diastolic ABPM value of 128.7+/-12.8/77.1+/
      9.2 mm Hg were evaluated. In backwards linear regression analyses adjusted for
      age, sex, body mass index, smoking, glomerular filtration rate, hemoglobin A1c ,
      N-terminal prohormone of brain natriuretic peptide, urinary sodium/potassium
      ratio, and ongoing antihypertensive medication, AARR was significantly associated
      with nocturnal systolic (beta-coefficient: 0.177; P=.017) and diastolic BP (beta
      coefficient: 0.162; P=.027). In patients with arterial hypertension, a
      significant association between AARR and nighttime BP even after adjustment for a
      broad panel of confounders was found. 

PMID- 24666973
TI  - Ultrasound study of carotid and cardiac remodeling and cardiac-arterial coupling
      in normal pregnancy and preeclampsia: a case control study.
AB  - BACKGROUND: Cardiovascular adaptions, such as cardiac and uterine spiral arterial
      remodeling, and aortic arterial stiffening during pregnancy have been extensively
      investigated, while the interactions between the elastic artery and the left
      ventricle are poorly understood. This study was to evaluate the cardiac-arterial
      coupling in both normal pregnancy and preeclampsia using ultrasound techniques.
      METHODS: Twenty-three preeclamptic women with no antihypertensive treatment prior
      to admission, and 40 age- (27.2 +/- 3.0 y vs. 29.1 +/- 5.7 y, p = 0.0805) and
      gestational week- (35.6 +/- 3.4 wk vs. 34.8 +/- 3.6 wk, p = 0.3573) matched
      normotensive pregnant women were included. All women signed informed consent. All
      were nulliparas, had singleton pregnancies, and had no other risk factors for
      arterial stiffening. Carotid and cardiac ultrasound was performed using a
      MylabTwice ultrasound unit (Esaote, Italy). Cardiac and carotid remodeling and
      their associations were analyzed. Left ventriculo-carotid coupling was
      characterized by the ratio between the arterial elastance (Ea) and the left
      ventricular systolic elastance (Ees). Follow-up study was performed 16-20 months
      after parturition. RESULTS: Left ventricular and carotid arterial remodeling was
      seen more frequently in preeclamptic women than in normal pregnant controls (96%
      vs. 40%, 82% vs. 48%, both p < 0.0001). The relative carotid arterial wall
      thickness showed no significant difference between the two groups. However, the
      carotid cross-sectional area, a surrogate for carotid arterial mass, was
      significantly greater in preeclampsia than that in normal controls (11.23 +/-
      0.17 mm2 vs. 8.58 +/- 1.88 mm2, p < 0.00001). Carotid arterial stiffness and
      intima-media thickness correlated significantly with cardiac diastolic function
      parameters and blood pressures (p < 0.05). Both Ea and Ees were significantly
      greater in preeclampsia, compared with values in normal pregnant controls (Ea:
      2.41 +/- 0.57 mmHg/ml vs. 1.98 +/- 0.46 mmHg/ml, p = 0.0005; Ees: 11.68 +/- 9.51
      m/s2 vs. 6.91 +/- 6.13 m/s2, p = 0.002). However, there was no significant
      difference in the left ventriculo-carotid coupling index, Ea/Ees, between the two
      groups. Carotid remodeling persisted in both preeclamptic women and normal
      pregnant controls 16-20 months after parturition. CONCLUSIONS: Significant
      cardiac and carotid remodeling and similar left ventriculo-carotid coupling were
      observed in both preeclampsia and normal pregnancy. Carotid remodeling may
      persist postpartum. Further studies with larger populations are needed to confirm
      these findings.

PMID- 24666974
TI  - Bile acid malabsorption assessed by 7 alpha-hydroxy-4-cholesten-3-one in
      pediatric inflammatory bowel disease: correlation to clinical and laboratory
      findings.
AB  - BACKGROUND AND AIMS: Measurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in
      serum is a semiquantitative test for bile acid malabsorption (BAM). We have
      previously established pediatric normal values for C4 with an upper limit of
      normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test
      in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC).
      METHODS: C4 was measured using high performance liquid chromatography (HPLC) in
      fasting serum samples of 44 patients with CD (range 7-19 years) and 14 with UC (4
      18 years). Disease activity was assessed by the pediatric CD and UC activity
      indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal
      inflammatory markers (calprotectin). RESULTS: C4 concentrations were increased in
      10 CD (23%) (range: 70.8-269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD
      patients with diarrhea (n=12) had higher C4-values compared to those without
      (76.9 vs. 30.4 ng/mL; p=0.0043). Ileal resection in CD patients (n=10) was
      associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p=0.0004). No
      correlation was found between C4 values and inflammatory markers. Six of 7 CD
      patients with persistent diarrhea but quiescent disease (PCDAI <=12.5) had C4
      values indicating BAM. CONCLUSION: Elevated C4 concentrations indicating BAM are
      common in children with CD. They are associated with ileal resection and non
      bloody diarrhea in the absence of active disease or elevated inflammatory
      markers. The C4-test identifies a subgroup of CD patients with persistent
      diarrhea in spite of clinical remission which may benefit from bile acid binding
      therapy.

PMID- 24666975
TI  - Vitamin D deficiency in Crohn's disease and healthy controls: a prospective case
      control study in the Netherlands.
AB  - BACKGROUND AND AIMS: Vitamin D deficiency has been observed in a wide range of
      medical conditions including Crohn's disease (CD). We aimed to assess whether CD
      patients have lower vitamin D levels than healthy controls, and to determine risk
      factors for vitamin D deficiency. METHODS: 25(OH)D was measured by
      chemiluminescent immunoassay in serum obtained from 101 CD patients and 41
      controls. Demographics, sunlight exposure, dietary vitamin D intake,
      comorbidities and medication were recorded using validated questionnaires. In CD
      patients the Harvey-Bradshaw index, Montreal classification and surgical
      resections were also evaluated. 25(OH)D levels of > 75 nmol/L, between 50 and 75
      nmol/L and < 50 nmol/L were considered as normal, suboptimal and deficient,
      respectively. RESULTS: Vitamin D levels were rather low but comparable among CD
      patients and controls (mean 25(OH)D 51.6 nmol/L(+/- 26.6) in CD, and 60.8
      nmol/L(+/- 27.6) in controls. Multivariate regression analysis revealed BMI, sun
      protection behaviour, non-Caucasian ethnicity, no use of tanning beds, and no
      holidays in the last year as significantly associated with serum 25(OH)D levels
      in CD patients (R=0.62). In the control group no statistically significant
      factors were identified that had an impact on 25(OH)D serum levels. CONCLUSIONS:
      Vitamin D deficiency is common in CD patients, but also in healthy controls.
      Appropriate vitamin D screening should be advised in patients with CD. Moreover,
      the positive effect of sunlight on the vitamin D status should be discussed with
      CD patients, but this should be balanced against the potential risk of developing
      melanomas, especially in patients using thiopurines.

PMID- 24666976
TI  - Sequential capsule endoscopy of the small bowel for follow-up of patients with
      known Crohn's disease.
AB  - BACKGROUND AND AIMS: The aim of this study was to perform sequential small bowel
      (SB) capsule endoscopy (CE) studies in patients with known active Crohn's disease
      (CD) during different treatments, to characterize the changes in the SB mucosa
      over time, and to correlate the CE findings with clinical and laboratory
      parameters of inflammation. METHODS: Consecutive patients with known moderately
      active CD were prospectively recruited. After proven patency with Agile capsule,
      CE studies were performed at baseline and after 4, 12 and 24 weeks. CE parameters
      and a Lewis score were calculated. Clinical and laboratory parameters were
      correlated. A control group of 178 non-CD patients was used for comparisons.
      RESULTS: Thirty-one CD patients were recruited and 19 met the inclusion criteria.
      A total of 43 CE studies were performed over the time. There was no capsule
      retention despite a high rate of previous SB surgery. The mean baseline CDAI,
      IBDQ and Lewis scores were 306+/-56, 135+/-26.6 and 1730+/-1780, respectively.
      There was no correlation at the baseline between clinical and laboratory
      parameters (CDAI, CRP, IBDQ) and mucosal disease (Lewis scores). CDAI and IBDQ
      changes over a period of 4 and 12 weeks did not correlate with the Lewis score.
      The cecum arrival rate of the CD patients was significantly lower (p=0.0047) and
      the SB transit time was significantly longer (p=0.005) compared to those of the
      controls. CONCLUSIONS: Sequential CE studies are feasible and safe in CD
      patients. In patients with complete CE studies, they provide reliable information
      on mucosal changes in CD and should be considered as an independent and objective
      follow-up tool in known CD patients.

PMID- 24666977
TI  - Surgical treatment of a brown recluse spider bite: a case study and literature
      review.
AB  - Spider bite envenomation can cause local, constitutional, and/or systemic
      symptoms. The present case study reports on 5 years of follow-up for a "probable"
      brown recluse spider bite of the foot and ankle that was refractory to
      conservative treatment and was subsequently treated with surgery. The present
      case study reports the atypical occurrence of long-term peripheral neuropathy
      after necrotic arachnidism induced by "probable" brown recluse (Loxosceles
      recluse) envenomation, in a 46-year-old male. The state of published data
      suggests to minimize inflammation and tissue necrosis, prevent bacterial
      superinfection, and control pain levels. For patients with long-term peripheral
      neuropathy refractory to conservative therapy, surgical intervention may further
      improve their symptoms. 

PMID- 24666978
TI  - Commercially available trabecular metal ankle interpositional spacer for
      tibiotalocalcaneal arthrodesis secondary to severe bone loss of the ankle.
AB  - Retrograde tibiotalocalcaneal nailing arthrodesis has proved to be a viable
      salvage procedure; however, extended bone loss around the ankle has been
      associated with high rates of nonunion and considerable shortening of the
      hindfoot. We present the surgical technique and the first 2 cases in which a
      trabecular metalTM interpositional spacer, specifically designed for
      tibiotalocalcaneal nailing arthrodesis, was used. The spacer can be implanted
      using either an anterior or a lateral approach. An integrated hole in the spacer
      allows a retrograde nail to be inserted, which provides excellent primary
      stability of the construct. Trabecular metalTM is a well-established and well
      described material used to supplement deficient bone stock in surgery of the
      spine, hip, and knee. It has shown excellent incorporation and reduces the need
      for auto- and allografts. The trabecular metalTM interpositional ankle spacer is
      the first trabecular metal spacer designed specifically for ankle surgery. Its
      shape and variable size will make it a valuable tool for reconstructing bone loss
      in tibiotalocalcaneal nailing arthrodesis. 

PMID- 24666979
TI  - Collagen ribbon augmentation of Achilles tendon tears: a biomechanical
      evaluation.
AB  - Early motion of a repaired Achilles tendon has been accepted to improve both
      clinical and biomechanical outcomes. It has been postulated that augmenting a
      primary Achilles tendon repair with a collagen ribbon will improve the repair
      construct's initial strength, thereby facilitating early motion. The purpose of
      the present study was to compare the failure load of Achilles tendon defects
      repaired with suture, with or without augmentation with a collagen ribbon. Ten
      matched pairs of cadaveric feet and tibiae underwent simulated Achilles tendon
      tear in the watershed area and were then repaired with 4-strand Krackow sutures
      only or were sutured and augmented with a box weave collagen ribbon xenograft.
      The specimens were prepared for testing by keeping the insertion of the Achilles
      to the calcaneus intact and dissecting the gastrocnemius at its origin, leaving
      the repair undisturbed. The mean load at failure for the augmented (suture plus
      collagen ribbon) specimens was 392.4 +/- 74.9 N. In contrast, the mean load at
      failure for the suture-only (control) construct was 98.0 +/- 17.6 N (p < .001).
      The augmented specimens demonstrated a greater mean strength of 4.1 +/- 0.9 N
      (range 3.2 to 5.6). After cyclic loading, the mean gap across the Achilles repair
      was significantly smaller in the augmented group than in the control group (p =
      .006). We have concluded that box weave collagen ribbon augmentation of the
      primary suture Achilles tendon repairs can provide enhanced gap resistance and
      strength under cyclic loading and ramped tensile testing. 

PMID- 24666980
TI  - Successful arthrodesis of the first metatarsophalangeal joint in patients with
      inflammatory and noninflammatory arthritis: a comparative analysis.
AB  - Arthrodesis of the first metatarsophalangeal (MTP) joint has been a reliable
      treatment option for end-stage osteoarthritis (OA) and rheumatoid arthritis (RA).
      The disease process is very different between these 2 types of degeneration. It
      is unknown whether first MTP fusions performed for each disease process will heal
      the same or differently. The purpose of the present study was to compare the
      fusion rate and interval to fusion between patients with first MTP OA and those
      with RA. The present study was an institutional review board-approved
      retrospective radiographic and medical record review funded by a not-for-profit
      educational research grant. The demographic and clinical variables were collected
      and compared between the 2 groups. A total of 155 first MTP fusion procedures for
      OA and RA were analyzed. Of these, 116 (74.83%) had been performed for pain from
      OA and 39 (25.16%) for RA. The RA group had a statistically significantly shorter
      interval to fusion than did those with OA (93 and 113 days, respectively; p =
      .025). The overall incidence of fusion for those with RA was 94% and for those
      with OA was 89%; however, this difference was neither clinically nor
      statistically significantly different (p = .36). The incidence of first MTP
      arthrodesis was high for both patients with OA and those with RA, and those with
      RA appeared to achieve fusion more rapidly. 

PMID- 24666981
TI  - Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an
      observational case series.
AB  - INTRODUCTION: Current guidelines for spontaneous intracerebral hemorrhage (ICH)
      recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg,
      depending on the state of autoregulation. We continuously assessed dynamic
      cerebral autoregulation and the possibility of determination of an optimal CPP
      (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and
      functional outcome were explored. METHODS: Intracranial pressure (ICP), mean
      arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with
      38 patients included in the analysis. The pressure reactivity index (PRx) was
      calculated as moving correlation between MAP and ICP. CPPopt was defined as the
      CPP associated with the lowest PRx values. CPPopt was calculated using hourly
      updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3
      months and associations between PRx, CPPopt and outcomes were explored using
      Pearson correlation and Fisher's exact test. Multivariate stepwise logistic
      regression models were calculated including standard outcome predictors along
      with percentage of time with PRx >0.2 and percentage of time within the CPPopt
      range. RESULTS: An overall PRx indicating impairment of pressure reactivity was
      found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx >
      0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46,
      P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median
      CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of
      patients with a CPP close to their CPPopt. However, for none of the CPPopt
      variables a significant association to outcome was found. The percentage of time
      with impaired autoregulation and hemorrhage volume were independent predictors
      for acceptable outcome (mRS 1 to 4) at three months. CONCLUSIONS: Failure of
      pressure reactivity seems common following severe ICH and is associated with
      unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might
      provide a tool for an autoregulation-oriented CPP management. A larger trial is
      needed to explore if a CPPopt management results in better functional outcomes.

PMID- 24666982
TI  - Circadian oscillatory transcriptional programs in grapevine ripening fruits.
AB  - BACKGROUND: Temperature and solar radiation influence Vitis vinifera L. berry
      ripening. Both environmental conditions fluctuate cyclically on a daily period
      basis and the strength of this fluctuation affects grape ripening too.
      Additionally, a molecular circadian clock regulates daily cyclic expression in a
      large proportion of the plant transcriptome modulating multiple developmental
      processes in diverse plant organs and developmental phases. Circadian cycling of
      fruit transcriptomes has not been characterized in detail despite their putative
      relevance in the final composition of the fruit. Thus, in this study, gene
      expression throughout 24 h periods in pre-ripe berries of Tempranillo and Verdejo
      grapevine cultivars was followed to determine whether different ripening
      transcriptional programs are activated during certain times of day in different
      grape tissues and genotypes. RESULTS: Microarray analyses identified oscillatory
      transcriptional profiles following circadian variations in the photocycle and the
      thermocycle. A higher number of expression oscillating transcripts were detected
      in samples carrying exocarp tissue including biotic stress-responsive transcripts
      activated around dawn. Thermotolerance-like responses and regulation of circadian
      clock-related genes were observed in all studied samples. Indeed, homologs of
      core clock genes were identified in the grapevine genome and, among them,
      VvREVEILLE1 (VvRVE1), showed a consistent circadian expression rhythm in every
      grape berry tissue analysed. Light signalling components and terpenoid
      biosynthetic transcripts were specifically induced during the daytime in Verdejo,
      a cultivar bearing white-skinned and aromatic berries, whereas transcripts
      involved in phenylpropanoid biosynthesis were more prominently regulated in
      Tempranillo, a cultivar bearing black-skinned berries. CONCLUSIONS: The
      transcriptome of ripening fruits varies in response to daily environmental
      changes, which might partially be under the control of circadian clock
      components. Certain cultivar and berry tissue features could rely on specific
      circadian oscillatory expression profiles. These findings may help to a better
      understanding of the progress of berry ripening in short term time scales.

PMID- 24666983
TI  - Molecular biology of K+ transport across the plant cell membrane: what do we
      learn from comparison between plant species?
AB  - Cloning and characterizations of plant K(+) transport systems aside from
      Arabidopsis have been increasing over the past decade, favored by the
      availability of more and more plant genome sequences. Information now available
      enables the comparison of some of these systems between species. In this review,
      we focus on three families of plant K(+) transport systems that are active at the
      plasma membrane: the Shaker K(+) channel family, comprised of voltage-gated
      channels that dominate the plasma membrane conductance to K(+) in most
      environmental conditions, and two families of transporters, the HAK/KUP/KT K(+)
      transporter family, which includes some high-affinity transporters, and the HKT
      K(+) and/or Na(+) transporter family, in which K(+)-permeable members seem to be
      present in monocots only. The three families are briefly described, giving
      insights into the structure of their members and on functional properties and
      their roles in Arabidopsis or rice. The structure of the three families is then
      compared between plant species through phylogenic analyses. Within clusters of
      ortologues/paralogues, similarities and differences in terms of expression
      pattern, functional properties and, when known, regulatory interacting partners,
      are highlighted. The question of the physiological significance of highlighted
      differences is also addressed. 

PMID- 24666984
TI  - Potassium K+ in plants.

PMID- 24666985
TI  - In vitro fermentation of feed ingredients by fresh or frozen pig fecal inocula.
AB  - In vitro techniques can offer a rapid, repeatable and cost-effective alternative
      to in vivo experiments. We investigated the gas production (GP) of nine different
      feeds commonly used in Italian and Maltese pig farms in order to assess the use
      of the Ankom system in this species and to compare the in vitro microbial
      activity fresh or frozen inocula derived from piglet feces. Proximate and
      polyphenolic analyses were determined for all substrates. Fermentation profiles
      were measured according to the cumulative GP technique. Analysis of GP values
      revealed significant differences in the fermentation patterns mainly due to
      substrate and inoculum effects. Fermentation parameters varied significantly
      according to the substrate ingredients. The frozen inoculum generally led to more
      total GP than for fresh, with the exception of hard wheat bran pellets (HWBP),
      pelleted pulp and mature carob. Conversely the fresh fecal inoculum had an
      earlier maximum time to reach maximum GP than the frozen, showing a higher
      maximum rate of GP in all substrates excepting for HWBP. A significant difference
      in frozen and fresh inocula was found for the complete formulation. Further
      studies are required to confirm the variation between fresh and frozen fecal
      inocula to a wider range of feed, including those that could have negative
      biological effects. 

PMID- 24666986
TI  - The role of clinical care pathways: an experience with distal pancreatectomy.
AB  - BACKGROUND: Previous studies have indicated that clinical pathways may shorten
      hospital length of stay (HLOS) among patients undergoing distal pancreatectomy
      (DP). Here, we evaluate an institutional standardized care pathway (SCP) for
      patients undergoing DP. MATERIALS AND METHODS: A retrospective review of patients
      undergoing DP from November 2006 to November 2012 was completed. Patients treated
      before and after implementation of the SCP were compared. Multivariable linear
      regression was then performed to identify independent predictors of HLOS.
      RESULTS: There were no differences in patient characteristics between SCP (n=50)
      and pre-SCP patients (n=100). Laparoscopic technique (62% versus 13%, P<0.001),
      splenectomy (52% versus 38%, P=0.117), and concomitant major organ resection (24%
      versus 13%, P=0.106) were more common among SCP patients. Overall, important
      complication rates were similar (24% versus 26%, P=0.842). SCP patients resumed a
      normal diet earlier (4 versus 5 d, P=0.025) and had shorter HLOS (6 versus 7 d,
      P=0.026). There was no increase in 30-d resurgery or readmission. In univariate
      comparison, SCP, cancer diagnoses, intraductal papillary mucinous neoplasm
      diagnoses, neoadjuvant therapy, operative technique, major organ resection, and
      feeding tube placement were associated with HLOS; however, after multivariable
      adjustment, only laparoscopic technique (-33%, P=0.001), concomitant major organ
      resection (+38%, P<0.001), and feeding tube placement (+68%, P<0.001) were
      independent predictors of HLOS. CONCLUSIONS: Implementation of a clinical pathway
      did not improve HLOS at our institution. The increasing use of laparoscopy likely
      accounts for shorter HLOS in the SCP cohort. In the future, it will be important
      to identify clinical scenarios most likely to benefit from implementation of a
      clinical pathway.

PMID- 24666987
TI  - Correlating surgical clerkship evaluations with performance on the National Board
      of Medical Examiners examination.
AB  - BACKGROUND: Evaluation of medical students during the surgical clerkship is
      controversial. Performance is often based on subjective scoring, whereas
      objective knowledge is based on written examinations. Whether these measures
      correspond or are relevant to assess student performance is unknown. We
      hypothesized that student evaluations correlate with performance on the National
      Board Of Medical Examiners (NBME) examination. METHODS: Data were collected from
      the 2011-2012 academic year. Medical students underwent a ward evaluation using a
      seven-point Likert scale assessing six educational competencies. Students also
      undertook the NBME examination, where performance was recorded as a percentile
      score adjusted to national standards. RESULTS: A total of 129 medical students
      were studied. Scores on the NBME ranged from the 52nd to the 96th percentile with
      an average in the 75th percentile (+/-9). Clerkship scores ranged from 3.2-7.0
      with a mean of 5.7 (+/-0.8). There was a strong positive association between
      higher NBME scores and higher clerkship evaluations shown by a Pearson
      correlation coefficient of 0.47 (P<0.001). Students clustered with below average
      ward evaluations (3.0-4.0) were in the 69.5th percentile of NBME scores, whereas
      students clustered with above average ward evaluations (6.0-7.0) were in the
      79.2th percentile (P<0.001). CONCLUSIONS: A strong positive relationship exists
      between subjective ward evaluations and NBME performance. These data may afford
      some confidence to surgical faculty and surgical resident ability to accurately
      evaluate medical students during clinical clerkships. Understanding factors in
      student performance may help in improving the surgical clerkship experience.

PMID- 24666988
TI  - Delirium prevention program in the surgical intensive care unit improved the
      outcomes of older adults.
AB  - BACKGROUND: Hospital-acquired delirium is a known risk factor for negative
      outcomes in patients admitted to the surgical intensive care unit (SICU).
      Outcomes worsen as the duration of delirium increases. The purpose of this study
      was to evaluate the efficacy of a delirium prevention program and determine
      whether it decreased the incidence and duration of hospital-acquired delirium in
      older adults (age>50 y) admitted to the SICU. METHODS: A prospective pre- or post
      intervention cohort study was done at an academic level I trauma center. Older
      adults admitted to the SICU were enrolled in a delirium prevention program. Those
      with traumatic brain injury, dementia, or 0 d of obtainable delirium status were
      excluded from analysis. The intervention consisted of multidisciplinary
      education, a pharmacologic protocol to limit medications associated with
      delirium, and a nonpharmacologic sleep enhancement protocol. Primary outcomes
      were incidence of delirium and delirium-free days/30. Secondary outcomes were
      ventilator-free days/30, SICU length of stay (LOS), daily and cumulative doses of
      opioids (milligram, morphine equivalents) and benzodiazepines (milligram,
      lorazepam equivalents), and time spent in severe pain (greater than or equal to 6
      on a scale of 1-10). Delirium was measured using the Confusion Assessment Method
      for the ICU. Data were analyzed using Chi-squared and Wilcoxon rank sum analysis.
      RESULTS: Of 624 patients admitted to the SICU, 123 met inclusion criteria: 57
      preintervention (3/12-6/12) and 66 postintervention (7/12-3/13). Cohorts were
      similar in age, gender, ratio of trauma patients, and Injury Severity Score.
      Postintervention, older adults experienced delirium at the same incidence (pre
      47% versus 58%, P=0.26), but for a significantly decreased duration as indicated
      by an increase in delirium-free days/30 (pre 24 versus 27, P=0.002). After
      intervention, older adults with delirium had more vent-free days (pre 21 versus
      25, P=0.03), shorter SICU LOS (pre 13 [median 12] versus 7 [median 6], P=0.01)
      and were less likely to be treated with benzodiazepines (pre 85% versus 63%,
      P=0.05) with a lower daily dose when prescribed (pre 5.7 versus 3.6 mg, P=0.04).
      After intervention, all older adults spent less time in pain (pre 4.7 versus 3.1
      h, P=0.02), received less total opioids (pre 401 versus 260 mg, P=0.01), and had
      shorter SICU LOS (pre 9 [median 5] versus 6 [median 4], P=0.04). CONCLUSIONS:
      Although delirium prevention continues to be a challenge, this study successfully
      decreased the duration of delirium for older adults admitted to the SICU. Our
      simple, cost-effective program led to improved pain and sedation outcomes. Older
      adults with delirium spent less time on the ventilator and all patients spent
      less time in the SICU.

PMID- 24666989
TI  - Variation in ambulatory surgery utilization in Michigan.
AB  - BACKGROUND: The practice of ambulatory surgery has expanded greatly as a result
      of advances in surgical technology and rising financial pressures. We sought to
      characterize the utilization of ambulatory surgical practices for common general
      surgical procedures in Michigan. MATERIALS AND METHODS: We identified 33,655
      patients within the Michigan Surgery Quality Collaborative clinical registry
      undergoing general surgical procedures performed on an ambulatory basis between
      25% and 75% of the time. Our primary outcome was the incidence of ambulatory
      surgery. Using multilevel mixed-effects logistic regression models, we adjusted
      ambulatory surgery utilization rates for patient comorbidities, procedure
      composition, and hospital characteristics. We then assessed the incidence of
      postoperative complications across hospitals grouped by their ambulatory surgery
      utilization rates. RESULTS: Adjusted utilization rates of ambulatory surgery
      varied widely across 34 hospitals from 29%-75% (mean = 54%). Risk-adjusted
      complication rates for ambulatory cases were similar between hospitals performing
      the least (2.2%) and the most ambulatory surgery (2.3%, P = 0.365). Patient
      factors and hospital characteristics accounted for 23.3% of the between-hospital
      variability in ambulatory surgery utilization, whereas most variation was
      explained by effects at the surgeon level. CONCLUSIONS: Despite wide variation in
      ambulatory surgery utilization for general surgical procedures, we were unable to
      explain observed differences by patient comorbidities, case mix, or hospital
      characteristics. These data suggest that understanding factors associated with
      ambulatory surgery utilization may represent a novel avenue for quality
      improvement within our statewide surgical collaborative.

PMID- 24666990
TI  - Predictive factors and models for trauma patient disposition.
AB  - BACKGROUND: Hospital length of stay for trauma patients can be unnecessarily
      prolonged due to delays in disposition planning. Demographic characteristics,
      comorbidities, and other patient variables may help in planning early during
      hospitalization. MATERIALS AND METHODS: The data of 2836 trauma patients were
      retrospectively analyzed. Analysis of variance and the chi-square test were used
      to determine univariate predictors of discharge location (i.e., home, nonhome,
      and rehabilitation), and multivariable logistic regression was used to determine
      independent predictors. Clinical decision rules for discharge location were
      developed for two models: (1) a regular discharge (RD) model to predict discharge
      location based on demographic and clinical characteristics at the completion of
      hospital stay and (2) an admission planning discharge (APD) model based on data
      available shortly after admission. RESULTS: The discharge locations differed on
      age, sex, certain comorbidities, and various hospital and clinical variables.
      Increased age, female sex, longer intensive care unit and hospital stays, and the
      comorbidities of neurologic deficiencies, coagulopathy, and diabetes were
      independent predictors of nonhome discharge in the RD model. For the APD model,
      increased age, female sex, the comorbidities of neurologic deficiencies,
      diabetes, coagulopathy, and obesity were independent predictors of nonhome
      discharge. The RD and APD models correctly predicted the discharge location 87.2%
      and 82.9% of the time, respectively. CONCLUSIONS: Demographic and clinical
      information for trauma patients predicts disposition early in the hospital stay.
      If the clinical decision rules are validated, discharge steps can be taken
      earlier in the hospital course, resulting in increased patient satisfaction,
      timely rehabilitation, and cost savings.

PMID- 24666992
TI  - Spray-coated nanoscale conductive patterns based on in situ sintered silver
      nanoparticle inks.
AB  - Nanoscale patterns with high conductivity based on silver nanoparticle inks were
      fabricated using spray coating method. Through optimizing the solution content
      and spray operation, accurate nanoscale patterns consisting of silver
      nanoparticles with a square resistance lower than 1 Omega /cm2 were obtained. By
      incorporating in situ sintering to substitute the general post sintering process,
      the time consumption could be significantly reduced to one sixth, qualifying it
      for large-scale and cost-effective fabrication of printed electronics. To testify
      the application of spray-coated silver nanoparticle inks, an inverted polymer
      solar cell was also fabricated, which exhibited a power conversion efficiency of
      2.76%. 

PMID- 24666991
TI  - Prevalence, predictors and outcome of hypofibrinogenaemia in trauma: a
      multicentre observational study.
AB  - INTRODUCTION: Exsanguination due to trauma-induced coagulopathy is a continuing
      challenge in emergency trauma care. Fibrinogen is a crucial factor for
      haemostatic competence, and may be the factor that reaches critically low levels
      first. Early fibrinogen substitution is advocated by a number of authors. Little
      evidence exists regarding the indications for fibrinogen supplementation in the
      acute phase. This study aims to estimate the prevalence of hypofibrinogenaemia in
      a multi-center trauma population, and to explore how initial fibrinogen
      concentration relates to outcome. Also, factors contributing to low fibrinogen
      levels are identified. METHODS: Patients arriving in hospital less than 180
      minutes post-injury requiring full trauma team activation in four different
      centers were included in the study. Time from injury, patient demographics,
      injury severity scores (ISS) and 28 days outcome status were recorded. Initial
      blood samples for coagulation and blood gas were analyzed. Generalized additive
      regression, piecewise linear regression, and multiple linear regression models
      were used for data analyses. RESULTS: Out of 1,133 patients we identified a
      fibrinogen concentration <=1.5g/L in 8.2%, and <2 g/L in 19.2%. A non-linear
      relationship between fibrinogen concentration and mortality was detected in the
      generalized additive and piecewise linear regression models. In the piecewise
      linear regression model we identified a breakpoint for optimal fibrinogen
      concentration at 2.29 g/L (95% confidence interval (CI): 1.93 to 2.64). Below
      this value the odds of death by 28 days was reduced by a factor of 0.08 (95% CI:
      0.03 to 0.20) for every unit increase in fibrinogen concentration. Low age, male
      gender, lengthened time from injury, low base excess and high ISS were unique
      contributors to low fibrinogen concentrations on arrival. CONCLUSIONS:
      Hypofibrinogenaemia is common in trauma and strongly associated with poor
      outcome. Below an estimated critical fibrinogen concentration value of 2.29 g/L a
      dramatic increase in mortality was detected. This finding indicates that the
      negative impact of low fibrinogen concentrations may have been previously
      underestimated. A number of clinically identifiable factors are associated with
      hypofibrinogenaemia. They should be considered in the management of massively
      bleeding patients. Interventional trials with fibrinogen substitution in high
      risk patients need to be undertaken.

PMID- 24666993
TI  - Ruscogenin ameliorates diabetic nephropathy by its anti-inflammatory and anti
      fibrotic effects in streptozotocin-induced diabetic rat.
AB  - BACKGROUND: Ruscogenin is a major steroid sapogenin in the traditional Chinese
      herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have
      demonstrated that ruscogenin is involved in down-regulation of intercellular
      adhesion molecule-1 (ICAM-1) and nuclear factor-kappaB (NF-kappaB) activation in
      anti-inflammatory pathways. We hypothesized that ruscogenin protects against
      diabetic nephropathy (DN) by inhibiting NF-kappaB-mediated inflammatory pathway.
      To test this hypothesis, the present study was to examine the effects of
      ruscogenin in rats with streptozotocin (STZ)-induced DN. METHODS: Diabetes was
      induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after
      STZ injection, rats in the treatment group were orally dosed with 0.3, 1.0 or 3.0
      mg/kg ruscogenin for 8 weeks. The normal rats were chosen as nondiabetic control
      group. The rats were sacrificed 10 weeks after induction of diabetes. Changes in
      renal function-related parameters in plasma and urine were analyzed at the end of
      the study. Kidneys were isolated for pathology histology, immunohistochemistry,
      and Western blot analyses. RESULTS: Ruscogenin administration did not lower the
      levels of plasma glucose and glycosylated hemoglobin in STZ-diabetic rats.
      Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine
      clearance, blood urea nitrogen and proteinuria, along with marked elevation in
      the ratio of kidney weight to body weight, that were reversed by ruscogenin.
      Ruscogenin treatment was found to markedly improve histological architecture in
      the diabetic kidney. Renal NF-kappaB activity, as wells as protein expression and
      infiltration of macrophages were increased in diabetic kidneys, accompanied by an
      increase in protein content of intercellular adhesion molecule-1 and monocyte
      chemoattractant protein-1 in kidney tissues. All of the above abnormalities were
      reversed by ruscogenin treatment, which also decreased the expression of
      transforming growth factor-beta1 and fibronectin in the diabetic kidneys.
      CONCLUSIONS: Our data demonstrated that ruscogenin suppressed the inflammation
      and ameliorated the structural and functional abnormalities of the diabetic
      kidney in rats might be associated with inhibition of NF-kappaB mediated
      inflammatory genes expression.

PMID- 24666994
TI  - Ultrastructure of UVR-B-induced cataract and repair visualized with electron
      microscopy.
AB  - PURPOSE: The aim of the study is to investigate and visualize the ultrastructure
      of cataract morphology and repair, after in vivo exposure to double threshold
      dose UVR-B in the C57BL/6 mouse lens. METHODS: Twenty-six-week-old C57BL/6 mice
      received in vivo double threshold dose (6.4 kJ/m2) UVR-B for 15 min. The
      radiation output of the UVR-source had lambdaMAX at 302.6 nm. After a latency
      period of 1, 2, 4 and 8 days following UVR-B exposure, the induced cataract was
      visualized with electron microscopy techniques. Induced, cataract was quantified
      as forward lens light scattering. Damage to the lens epithelium and the anterior
      cortex was investigated with light microscopy in toluidine blue-stained semi-thin
      sections, transmission electron microscopy (TEM), scanning electron microscopy
      (SEM) and dark field illumination photography. RESULTS: UVR-B-exposed lenses
      developed anterior subcapsular and/or cortical and nuclear cataract after 1 day.
      Lens light scattering peaked 2 days after exposure. Lens epithelial cell damage
      was seen in TEM as apoptotic cells, apoptotic bodies, nuclear chromatin
      condensation, and swollen and disrupted anterior cortex fibres throughout the
      sections of the whole anterior lens surface. These morphologic changes were also
      visualized with SEM. Within 8 days, anterior subcapsular cataract was repaired
      towards the anterior sutures. CONCLUSION: UVR-B exposure of double cataract
      threshold dose induces a subtotal loss of epithelial cells across the whole
      anterior surface of the lens. This damage to the epithelium is repaired by
      epithelial cell movement from the equator towards the lens sutures, thus in
      retrograde direction to regular epithelial cell differentiation.

PMID- 24666996
TI  - Plasmodial Hsp40 and Hsp70 chaperones: current and future perspectives.
AB  - Plasmodium falciparum displays a large and remarkable variety of heat shock
      protein 40 family members (PfHsp40s). The majority of the PfHsp40s are poorly
      characterized, and although the functions of some of them have been suggested,
      their exact mechanism of action is still elusive and their interacting partners
      and client proteins are unknown. The P. falciparum heat shock protein 70 family
      members (PfHsp70s) have been more extensively characterized than the PfHsp40s,
      with certain members shown to function as molecular chaperones. However, little
      is known about the PfHsp70-PfHsp40 chaperone partnerships. There is mounting
      evidence that these chaperones are important not only in protein homoeostasis and
      cytoprotection, but also in protein trafficking across the parasitophorous
      vacuole (PV) and into the infected erythrocyte. We propose that certain members
      of these chaperone families work together to maintain exported proteins in an
      unfolded state until they reach their final destination. In this review, we
      critically evaluate what is known and not known about PfHsp40s and PfHsp70s.

PMID- 24666995
TI  - Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo
      and in vitro gut epithelia.
AB  - BACKGROUND: TiO2 particles are commonly used as dietary supplements and may
      contain up to 36% of nano-sized particles (TiO2-NPs). Still impact and
      translocation of NPs through the gut epithelium is poorly documented. RESULTS: We
      show that, in vivo and ex vivo, agglomerates of TiO2-NPs cross both the regular
      ileum epithelium and the follicle-associated epithelium (FAE) and alter the
      paracellular permeability of the ileum and colon epithelia. In vitro, they
      accumulate in M-cells and mucus-secreting cells, much less in enterocytes. They
      do not cause overt cytotoxicity or apoptosis. They translocate through a model of
      FAE only, but induce tight junctions remodeling in the regular ileum epithelium,
      which is a sign of integrity alteration and suggests paracellular passage of NPs.
      Finally we prove that TiO2-NPs do not dissolve when sequestered up to 24 h in gut
      cells. CONCLUSIONS: Taken together these data prove that TiO2-NPs would possibly
      translocate through both the regular epithelium lining the ileum and through
      Peyer's patches, would induce epithelium impairment, and would persist in gut
      cells where they would possibly induce chronic damage.

PMID- 24666997
TI  - Phylogenetic analysis of pectin-related gene families in Physcomitrella patens
      and nine other plant species yields evolutionary insights into cell walls.
AB  - BACKGROUND: Pectins are acidic sugar-containing polysaccharides that are
      universally conserved components of the primary cell walls of plants and modulate
      both tip and diffuse cell growth. However, many of their specific functions and
      the evolution of the genes responsible for producing and modifying them are
      incompletely understood. The moss Physcomitrella patens is emerging as a powerful
      model system for the study of plant cell walls. To identify deeply conserved
      pectin-related genes in Physcomitrella, we generated phylogenetic trees for 16
      pectin-related gene families using sequences from ten plant genomes and analyzed
      the evolutionary relationships within these families. RESULTS: Contrary to our
      initial hypothesis that a single ancestral gene was present for each pectin
      related gene family in the common ancestor of land plants, five of the 16 gene
      families, including homogalacturonan galacturonosyltransferases,
      polygalacturonases, pectin methylesterases, homogalacturonan methyltransferases,
      and pectate lyase-like proteins, show evidence of multiple members in the early
      land plant that gave rise to the mosses and vascular plants. Seven of the gene
      families, the UDP-rhamnose synthases, UDP-glucuronic acid epimerases,
      homogalacturonan galacturonosyltransferase-like proteins, beta-1,4-galactan beta
      1,4-galactosyltransferases, rhamnogalacturonan II xylosyltransferases, and pectin
      acetylesterases appear to have had a single member in the common ancestor of land
      plants. We detected no Physcomitrella members in the xylogalacturonan
      xylosyltransferase, rhamnogalacturonan I arabinosyltransferase, pectin
      methylesterase inhibitor, or polygalacturonase inhibitor protein families.
      CONCLUSIONS: Several gene families related to the production and modification of
      pectins in plants appear to have multiple members that are conserved as far back
      as the common ancestor of mosses and vascular plants. The presence of multiple
      members of these families even before the divergence of other important cell wall
      related genes, such as cellulose synthases, suggests a more complex role than
      previously suspected for pectins in the evolution of land plants. The presence of
      relatively small pectin-related gene families in Physcomitrella as compared to
      Arabidopsis makes it an attractive target for analysis of the functions of
      pectins in cell walls. In contrast, the absence of genes in Physcomitrella for
      some families suggests that certain pectin modifications, such as
      homogalacturonan xylosylation, arose later during land plant evolution.

PMID- 24666998
TI  - Absolute lymphocyte count: a potential prognostic factor for Merkel cell
      carcinoma.
AB  - BACKGROUND: Absolute lymphocyte count (ALC) is a laboratory value commonly
      obtained during workup of patients with Merkel cell carcinoma (MCC). OBJECTIVE:
      We report the prognostic impact of ALC as a surrogate of immune status in MCC.
      METHODS: A complete blood cell count was available for 64 patients with MCC in
      the month before definitive surgery, chemotherapy, or radiation. Statistical
      analysis was performed with classification and regression tree analysis, log rank
      test, and Cox model. RESULTS: Median overall survival (OS) for the cohort was 97
      months. Median OS for patients with an ALC less than 1.1 k/mm(3) was 18.8 versus
      110.1 months for those with ALC greater than or equal to 1.1 k/mm(3) (P = .002,
      hazard ratio 0.29). Multivariate analysis of OS controlling for ALC, sex, stage,
      adjuvant chemotherapy, hematologic malignancy, and immunosuppression demonstrated
      ALC as a prognostic factor (P = .03). Disease-free survival at 36 months for ALC
      less than 1.1 k/mm(3) was 26.9% versus 64.4% for those with ALC greater than or
      equal to 1.1 k/mm(3) (P = .01). ALC was not a significant predictor for disease
      free survival on multivariate analysis (P = .12). LIMITATIONS: This is a single
      institution retrospective data set. CONCLUSION: ALC is associated with OS but not
      disease-free survival in MCC using a threshold of less than 1.1 k/mm(3). This
      test may provide additional prognostic information for patients with MCC.

PMID- 24666999
TI  - High-risk single ventricle palliation in children with Down syndrome: single
      institution experience.
AB  - BACKGROUND: Of the children with Down syndrome 40-50% have cardiac defects and
      the majority of these cardiac defects are amenable to biventricular repair. The
      outcome of single ventricle palliation is improving; nonetheless, there are
      limited data on Down syndrome patients with associated high-risk factors
      undergoing single ventricle palliation. Our aim was to study the outcomes of
      children with Down syndrome and high-risk factors on the single ventricle
      palliation pathway. METHODS: A retrospective study on all patients with Down
      syndrome on the single ventricle palliation pathway from 2005 until 2011 was
      conducted. Operative, clinical, echocardiographic, haemodynamic data, and follow
      up data were reviewed. RESULTS: A total of 310 patients underwent at least one
      single ventricle surgical intervention. Of those, eight patients had Down
      syndrome, five of which had associated risk factors - low birth weight, high
      pulmonary vascular resistance, pulmonary vein stenosis, significant
      atrioventricular valve regurgitation, and extracardiac anomalies. Mortality in
      the high-risk group was 80% (4/5), compared with 33% (1/3) in the non-high-risk
      patients. Overall, after a median follow-up period of 138 days (8-576 days), only
      37.5% (3/8) of patients were alive. CONCLUSION: Despite many improvements in the
      care of single ventricle patients, the fate of those with Down syndrome and
      associated high-risk factors remains poor. Further multicentre longer-term
      studies are needed to validate and quantify the cumulative effects of negative
      prognostic factors in this complex group of patients.

PMID- 24667000
TI  - The oxidative status and inflammatory level of the peripheral blood of rabbits
      infested with Psoroptes cuniculi.
AB  - BACKGROUND: Psoroptes cuniculi can parasitise the ear canal of the rabbit, and
      cause the afflicted animals to cease feeding and become severely debilitated,
      sometimes resulting in death. In this study, we examined the oxidative status and
      inflammatory level of the peripheral blood of rabbits infested with Psoroptes
      cuniculi and investigated the pathogenesis of this disease. METHODS: A total of
      24 rabbits were divided into a healthy rabbit group and two infested rabbit
      groups. After weighing the rabbits, approximately 5 ml of blood was obtained from
      each animal. Then, the blood serum was extracted and used to assess the levels of
      antioxidant enzymes and inflammatory factors. RESULTS: Compared to the healthy
      rabbits, the activities of catalase and glutathione-S-transferase and the level
      of malonyldialdehyde were increased, but the activity of superoxide dismutase was
      reduced in the infested rabbits. At the same time, a variety of inflammatory
      cells were activated, and the levels of inflammatory factors such as
      prostaglandin E2, interleukin-6, interleukin-8 and transforming growth factor
      beta1 were increased in peripheral blood. CONCLUSION: Animal acariasis was
      associated with immunosuppressive disorders and inflammatory reaction. These
      results advance our understanding of the pathogenesis of Psoroptes cuniculi
      infestation in rabbits and can help guide the effectual treatment of this disease
      in clinics.

PMID- 24667001
TI  - Is antenatal care preparing mothers to care for their newborns? A community-based
      cross-sectional study among lactating women in Masindi, Uganda.
AB  - BACKGROUND: Neonatal mortality has remained resistant to change in the wake of
      declining child mortality. Suboptimal newborn care practices are predisposing
      factors to neonatal mortality. Adherence to four ANC consultations is associated
      with improved newborn care practices. There is limited documentation of this
      evidence in sub-Saharan Africa where suboptimal newborn care practices has been
      widely reported. METHODS: Structured interviews were held with 928 women having
      children under-five months old at their homes in Masindi, Uganda, from October
      December 2011. Four/more ANC consultations (sufficient ANC) was considered the
      exposure variable. Three composite variables (complete cord care, complete
      thermal care and complete newborn vaccination status) were derived by combining
      related practices from a list of recommended newborn care practices. Logistic
      regression models were used to assess for associations. RESULTS: One in five
      women 220(23.7%) were assessed to practice complete cord care. Less than ten
      percent 57(6.1%) were considered to practice complete thermal care and 611(65.8%)
      were assessed to have complete newborn vaccination status. Application of
      substance on the cord 744 (71.6%) and early bathing 816 (87.9%) were main drivers
      of sub-optimal newborn care practices. Multivariable logistic models did not
      demonstrate significant association between four/more ANC consultations and
      complete cord care, complete thermal care or complete newborn vaccination status.
      Secondary or higher education was associated with complete cord care [adjusted
      Odds Ratio (aOR): 2.72; 95% CI: 1.63-4.54] and complete newborn vaccination [aOR:
      1.37; 95% CI: 1.04-1.82]. Women who reported health facility delivery were more
      likely to report complete thermal care [aOR: 3.63; 95% CI: 2.21-5.95] and newborn
      vaccination [aOR: 1.84; 95% CI: 1.23-2.75], but not complete cord care. Having
      the first baby was associated with complete thermal care [aOR: 2.00; 95% CI: 1.24
      3.23]. CONCLUSION: Results confirm suboptimal newborn care practices in Masindi.
      Despite being established policy, adherence to four or more ANC consultations was
      not associated with complete cord care, complete thermal care or complete newborn
      vaccination. This finding has important implications for the implementation of
      focused ANC to improve newborn care practices. Future ANC interventions should
      focus on addressing application of substance on the cord and early bathing of the
      baby during the immediate neonatal period.

PMID- 24667002
TI  - Early osmotic adjustment responses in drought-resistant and drought-sensitive
      oilseed rape.
AB  - The impact of osmotic stress on growth, physiology, and metabolism of winter
      oilseed rape (Brassica napus L.) was investigated by detailed analysis of biomass
      traits, hormone metabolites and osmolytes in two genetically unrelated drought
      tolerant genotypes and two unrelated drought-sensitive genotypes. Seedlings were
      grown in vitro under controlled conditions and osmotic stress was simulated by
      applying a gradual treatment with polyethylene glycol (PEG 6000), followed by
      hypo-osmotic treatment of variants used for metabolite determination. The results
      provide a basis for the identification of reliable selection criteria for drought
      resistance in oilseed rape. The in vitro cultivation system established during
      this study enabled effective discrimination of early osmotic stress responses
      between drought-resistant and -susceptible oilseed rape genotypes that also show
      large differences in relative seed yield under drought conditions in the field.
      Clear physiological and metabolic differences were observed between the drought
      resistant and drought-sensitive genotypes, suggesting that osmotic adjustment is
      a key component of drought response in oilseed rape. Unexpectedly, however, the
      drought-resistant genotypes did not show typical hormonal adjustment and osmolyte
      accumulation, suggesting that they possess alternative physiological mechanisms
      enabling avoidance of stress symptoms. 

PMID- 24667003
TI  - Blood pressure and uric acid in diabetes mellitus.

PMID- 24667004
TI  - Therapeutic inertia in hypercholesterolaemia is associated with ischaemic events
      in primary care patients. A case-control study.
AB  - BACKGROUND: The frequency of therapeutic inertia (TI) is very high in the
      management of vascular risk factors, although its impact on the incidence of
      ischaemic events is not well-established. Our aim was to investigate the
      relationship between TI in the treatment of hypercholesterolaemia and the
      appearance of ischaemic events. METHODS: An observational, multicentre, case
      control study was conducted in 70 primary care centres in Spain. Case subjects (n
      = 235) were high-risk hypercholesterolaemic patients (both genders, >= 18 years)
      who had had a first event in the 12 months prior to recruitment. They were
      matched with 235 controls (by vascular risk, age and gender). The observation
      period was 18 months prior to the onset of a first event (cases) or to date of
      recruitment (control subjects). RESULTS: The TI in the basal visit (an average of
      7.8 months before the event) was slightly higher in cases than in controls (39.7%
      vs. 34.8%, NS). However, the accumulated TI was similar in both groups (70.7% for
      cases and 73.95% for controls, NS). The multivariate analysis, taking ischaemic
      events as the dependent variable, showed that the TI at baseline visit was
      significantly associated with the development of the event [OR 2.18 (95% CI 1.04
      4.51), p < 0.05]. Other variables also associated with the ischaemic event were a
      family history of premature vascular disease [OR 3.38 (95% CI 1.35-8.49), p <
      0.05] and uncontrolled hypertension [OR 2.35 (95% CI 1.02-5.43), p < 0.05].
      CONCLUSION: The TI in high-risk hypercholesterolaemic patients in primary
      prevention in Spanish primary care centres doubled the risk of an ischaemic event
      in the short term.

PMID- 24667005
TI  - Clinical and biological changes under treatment with lithium carbonate and
      valproic acid in sporadic amyotrophic lateral sclerosis.
AB  - The aim of this study was to evaluate the ability of lithium carbonate and
      valproate cotreatment to modify the survival rate and functional score of
      patients with definite sporadic amyotrophic lateral sclerosis (ALS). The clinical
      response of 18 enrolled patients was compared to the evolution of 31 ALS out
      patients, carefully paired by age, gender, evolution rate and time of the
      disease, who never received treatment with lithium and/or valproate. The ALS
      functional rating scale, revised version (ALSFRS-R), was applied at baseline, 1
      month, and every 4 months until the outcome (death or an adverse event).
      Biochemical markers, such as Cu/Zn superoxide dismutase and glutathione
      peroxidase activity, and reduced glutathione were assayed in plasma samples
      obtained at the baseline visit and after 5 and 9 months of treatment. Our results
      showed that lithium and valproate cotreatment significantly increased survival
      (p=0.016), and this treatment also exerted neuroprotection in our patients
      because all three markers reached levels that were not significantly different
      from the matched samples of healthy donors. The trial stopped after 21 months,
      when the sample was reduced to under two-thirds, due to the late adverse events
      of the treatment. The results call for large randomized clinical trials with the
      dual association, but at low doses to avoid adverse events.

PMID- 24667006
TI  - New pathways for an old molecule: the role of the Na+-K+ ATPase pump in
      peripheral neuropathy.

PMID- 24667007
TI  - Stuck in the middle with you: close concordance between geographical clines in a
      cricket hybrid zone.
AB  - Students of speciation have long recognized that hybridization between
      populations does not affect all parts of the genome in the same way (Key 1968,
      Bazykin 1969, Wu 2001, Nosil et al. 2009). For example, divergence is expected to
      be high at loci involved in Dobzhansky-Muller incompatibilities or at loci under
      divergent natural selection, while those that are effectively neutral should show
      only weak divergence. Studies that examine geographical clines at divergent loci
      in a hybrid zone can be particularly powerful, as here one can estimate how net
      selection is affecting each locus (Payseur 2010). An excellent example of this
      approach appears in this issue (Larson et al. 2014) for a hybrid zone between the
      crickets Gryllus firmus and Gryllus pennsylvanicus in the eastern United States.

PMID- 24667008
TI  - The shape of things to come in the study of the origin of species?
AB  - Perhaps Darwin would agree that speciation is no longer the mystery of mysteries
      that it used to be. It is now generally accepted that evolution by natural
      selection can contribute to ecological adaptation, resulting in the evolution of
      reproductive barriers and, hence, to the evolution of new species (Schluter &
      Conte 2009; Meyer 2011; Nosil 2012). From genes that encode silencing proteins
      that cause infertility in hybrid mice (Mihola et al. 2009), to segregation
      distorters linked to speciation in fruit flies (Phadnis & Orr 2009), or
      pollinator-mediated selection on flower colour alleles driving reinforcement in
      Texan wildflowers (Hopkins & Rausher 2012), characterization of the genes that
      drive speciation is providing clues to the origin of species (Nosil & Schluter
      2011). It is becoming apparent that, while recent work continues to overturn
      historical ideas about sympatric speciation (e.g. Barluenga et al. 2006),
      ecological circumstances strongly influence patterns of genomic divergence, and
      ultimately the establishment of reproductive isolation when gene flow is present
      (Elmer & Meyer 2011). Less clear, however, are the genetic mechanisms that cause
      speciation, particularly when ongoing gene flow is occurring. Now, in this issue,
      Franchini et al. (2014) employ a classic genetic mapping approach augmented with
      new genomic tools to elucidate the genomic architecture of ecologically divergent
      body shapes in a pair of sympatric crater lake cichlid fishes. From over 450
      segregating SNPs in an F2 cross, 72 SNPs were linked to 11 QTL associated with
      external morphology measured by means of traditional and geometric morphometrics.
      Annotation of two highly supported QTL further pointed to genes that might
      contribute to ecological divergence in body shape in Midas cichlids, overall
      supporting the hypothesis that genomic regions of large phenotypic effect may be
      contributing to early-stage divergence in Midas cichlids.

PMID- 24667009
TI  - Pool and conquer: new tricks for (c)old problems.
AB  - The early period of genetics is closely associated with the study of chromosomal
      inversions. For almost a century, evolutionary biologists found evidence for the
      role of inversions in central processes such as adaptation and speciation. In
      spite of huge efforts, many questions remain about the evolutionary forces
      underlying the distribution and dynamics of inversions in natural populations.
      Fortunately, old problems can be solved with new tools. In this issue, Kapun et
      al. (2014) present a remarkable combination of resources and techniques,
      including publicly available data, karyotyping, statistical estimation of
      haplotypes, Pool-Seq data and experimental evolution, setting the ground for
      exciting developments in the field.

PMID- 24667011
TI  - Impact of four sequential measures on the prevention of ventilator-associated
      pneumonia in cardiac surgery patients.
AB  - INTRODUCTION: Ventilator-associated pneumonia (VAP) is the most frequent
      infection in patients admitted to intensive care units. METHODS: We compared
      rates of VAP, days on mechanical ventilation (MV), and cost of antimicrobial
      agents before and during implementation. RESULTS: We collected data from 401
      patients before the intervention and from 1,534 patients during the intervention.
      Both groups were comparable. No significant differences in EuroSCORE were
      observed between the patients of both periods (6.4 versus 6.3; P = 0.7). The
      rates of VAP (episodes/1,000 days of ventilation) were, respectively, 23.9 versus
      13.5 (P = 0.005). Mean number of days of MV/1,000 days of stay was 507 versus 375
      (P = 0.001), and the cost of antimicrobial therapy (Euros/1,000 days of stay) was
      ?70,612 versus ?52,775 (P = 0.10). The main effect of sequential application of
      preventive measures in time achieved a relative-rate reduction of VAP of 41%
      (IRR, 0.41; 95% CI, 0.28 to 0.62). The mortality rate before and during the
      intervention was 13.0% and 10.2%, respectively. CONCLUSIONS: A sequentially
      applied bundle of four preventive measures reduces VAP rates, days of MV, and the
      cost of antimicrobial therapy in patients admitted to the major heart surgery
      ICU. TRIAL REGISTRATION: Clinical Trials.gov: NCT02060045. Registered 4 February
      2014.

PMID- 24667010
TI  - Nicotine dependence as a moderator of genetic influences on smoking cessation
      treatment outcome.
AB  - BACKGROUND: Genetic influences on smoking cessation treatment outcome may be
      affected by pretreatment patient characteristics. Nicotine dependence is arguably
      the most salient clinical factor in smoking cessation. METHODS: In this secondary
      analysis of clinical trial data (N=793), we examined nicotine dependence severity
      as a moderator of the effects of 1198 single nucleotide polymorphisms (SNPs) in
      53 biologically-relevant gene regions on smoking cessation outcomes. P-values
      were adjusted to account for multiple correlated SNPs within a gene region;
      corrected system-wide significance was 5 * 10(-4). RESULTS: SNP * nicotine
      dependence interactions reached region-wide significance for several SNPs in the
      Dopamine Beta Hydroxylase (DBH) locus (0.0005<Adjusted-P<0.05), including
      rs1541333, which reached system-wide significance for predicting end of treatment
      (EOT) abstinence (Adjusted-P=0.0004). A haplotype including 6 DBH SNPs predicted
      abstinence at EOT (OR=1.7, P=0.001) and 6-month follow-up (OR=1.6, P=0.008) in
      those with high nicotine dependence (n=526) but not in those with low dependence
      (n=227). The DBH signal observed here may be distinct from a previously reported
      genome-wide significant signal for former smoking status and from the principal
      haplotype associated with plasma dopamine beta-hydroxylase activity. A haplotype
      within the Chromosome 15 Nicotinic Acetylcholine Receptor gene region predicted
      abstinence at EOT in those with high (OR=2.0, P=0.0004) but not low (P=0.6)
      dependence in post hoc analyses. CONCLUSIONS: Considering pre-treatment nicotine
      dependence level may optimize the prediction of genetic influences on cessation
      outcomes. If replicated, results like these may inform prognosticative genomic
      screening panels designed to identify smokers at high risk of relapse when
      coupled with severe nicotine dependence.

PMID- 24667012
TI  - Comparison of mathematical morphological descriptors of hyporeflective cavities
      in optical coherence tomography of patients with macular telangiectasia compared
      to patients with diabetic maculopathy.

PMID- 24667013
TI  - Carboxymethyl chitosan-folic acid-conjugated Fe3O4@SiO2 as a safe and targeting
      antitumor nanovehicle in vitro.
AB  - A synthetic method to prepare a core-shell-structured Fe3O4@SiO2 as a safe
      nanovehicle for tumor cell targeting has been developed. Superparamagnetic iron
      oxide is encapsulated inside nonporous silica as the core to provide magnetic
      targeting. Carboxymethyl chitosan-folic acid (OCMCS-FA) synthesized through
      coupling folic acid (FA) with OCMCS is then covalently linked to the silica shell
      and renders new and improved functions because of the original biocompatible
      properties of OCMCS and the targeting efficacy of FA. Cellular uptake of the
      nanovehicle was assayed by confocal laser scanning microscope using rhodamine B
      (RB) as a fluorescent marker in HeLa cells. The results show that the surface
      modification of the core-shell silica nanovehicle with OCMCS-FA enhances the
      internalization of nanovehicle to HeLa cells which over-express the folate
      receptor. The cell viability assay demonstrated that Fe3O4@SiO2-OCMCS-FA
      nanovehicle has low toxicity and can be used as an eligible candidate for drug
      delivery system. These unique advantages make the prepared core-shell nanovehicle
      promising for cancer-specific targeting and therapy. 

PMID- 24667014
TI  - Control options for Neospora caninum--is there anything new or are we going
      backwards?
AB  - Recent work has highlighted and enumerated the economic annual losses due to
      Neospora caninum abortions worldwide, which should provide strong motivation for
      the control of bovine neosporosis. However, with the recent withdrawal from sale
      of the only commercially available vaccine, control options for N. caninum have
      become more restricted. While researchers continue to work on developing
      alternative efficacious vaccines, what are the control options presently
      available for the cattle industries? At the practical level, recommendations for
      'Test-and-cull', or 'not breeding from seropositive dams' stand diametrically
      opposed to alternative options put forward that suggest a primary producer is
      better advised to keep those cows in the herd that are already seropositive,
      i.e., assumed to be chronically infected, and indeed those that have already
      aborted once. Treatment with a coccidiostat has been recommended as the only
      economically viable option, yet no such treatment has gained official, regulatory
      approval. Dogs are central to the life cycle of N. caninum and have repeatedly
      been associated with infection and abortions in cattle by epidemiological
      studies. Knowledge and understanding of that pivotal role should be able to be
      put to use in control programmes. The present review canvasses the relevant
      literature for evidence for control options for N. caninum (some of them proven,
      many not) and assesses them in the light of the authors' knowledge and experience
      with control of N. caninum.

PMID- 24667015
TI  - The effect of acupuncture needle combination on central pain processing--an fMRI
      study.
AB  - BACKGROUND: Empirical acupuncture treatment paradigm for acute pain utilizing
      Tendinomuscular Meridians (TMM) calls for the stimulation of Ting Points (TPs)
      and Gathering point(GP). This study aims to compare the supraspinal neuronal
      mechanisms associated with both TPs and GP needling (EA3), and TPs needling alone
      (EA2) with fMRI. RESULTS: A significant (P < 0.01) difference between pre-scan
      (heat Pain) HP, and post-EA HP VAS scores in both paradigms was noted (n = 11).
      The post-EA HP VAS score was significantly (P < 0.05) lower with EA3 comparing to
      EA2 Within-group random effect analysis indicated that EA3+HP>EA3 (condition
      EA3+HP subtracted by condition EA3) appeared to exert a significant degree of
      activity suppression in the affective supraspinal regions including the IPL,
      anterior cingulate cortex (ACC) and the insular cortex (IN). This level of
      suppression was not observed in the EA2+HP>EA2 (condition EA2+HP subtracted by
      condition EA2) within-group random effect analysis Between-group random effect
      analysis indicated that EA3 induced a significantly (P < 0.01, cluster size
      threshold 150) higher degree of deactivation than EA2 in several pain related
      supraspinal regions including the right prefrontal cortex, rostral anterior
      cingulate (rACC), medial cingulate cortex, left inferior frontal lobe and
      posterior cerebellum. The 2-factor ANOVA in those regions indicated both rACC and
      posterior cerebellum had a significant (P < 0.01) needle effect, and the right
      prefrontal area showed a significant (P < 0.01) HP effect. However, a significant
      interaction between the two factors was only found in the right prefrontal lobe.
      Granger causality analysis showed EA3 induced a much higher degree of inference
      among HP related supraspinal somatosensory, affective and modulatory components
      than EA2. Deactivation pattern at the medullary-pontine area casted a direct
      inference on the deactivation pattern of secondary somatosensory cortices which
      also affected the deactivation of the IN. CONCLUSIONS: While both EA2 and EA3
      induced a significant degree of deactivation in the human brain regions related
      to pain processing, the addition of GP stimulation further exerts an inhibitory
      effect on the ascending spinoreticular pain pathway. Therefore, different
      needling position as mandated in different empirical acupuncture treatment
      paradigms may play a different role in modulating pain related neuronal
      functions.

PMID- 24667017
TI  - Feasibility of implementing a meditative movement intervention with bariatric
      patients.
AB  - Successful interventions are needed to help improve obesity rates in the United
      States. Roughly two-thirds of adults in the United States are overweight, and
      almost one-third are obese. In 1991, the National Institutes of Health released a
      consensus statement endorsing bariatric surgery as the only means for sustainable
      weight loss for severely obese patients. However, approximately one-third of
      bariatric patients will experience significant post surgical weight gain. PURPOSE
      OF STUDY: This study is designed to determine if meditative movement (MM) would
      be a feasible physical activity (PA) modality to initiate weight loss in
      bariatric surgery patients who have re-gained weight. METHODS USED: A feasibility
      study was recently completed in 39 bariatric patients at Scottsdale Bariatric
      Center (SBC) during regularly scheduled bariatric support groups at SBC. A short
      demonstration of MM was presented after which a short focus group was conducted
      to gauge interest level, acceptability and the potential demand for MM programs
      in this population. Attitudes and intentions surrounding MM were also collected.
      FINDINGS: Approximately 75% of participants indicated they would consider
      practicing MM as part of their post surgical PA routine. CONCLUSIONS: MM may be a
      feasible PA modality in bariatric patients to improve bariatric surgery weight
      outcomes.

PMID- 24667016
TI  - Urine pi-Glutathione S-transferase but not Tamm-Horsfall protein correlates with
      carotid artery intima media thickness in childhood type1 diabetes.
AB  - BACKGROUND: Renal disease remains a serious threat in patients with insulin
      dependent (type1) diabetes. Hence its detection early in the life of patients
      with type1 diabetes is crucial. Several lines of evidence suggest similar
      mechanisms for the development of both renal and arterial disease. We sought to
      investigate in young patients with type1 diabetes whether pi-Glutathione S
      transferase to creatinine (pi-GST:crea) and Tamm-Horsfall protein to creatinine
      (THP:crea) ratios, markers of distal tubular renal function, relate to
      subclinical markers of arterial disease, which appear to onset early and develop
      rapidly in type1 diabetes. METHODS: Seventy-one children and adolescents (median
      age and diabetes duration 14 and 6 years, respectively) with type1 diabetes for
      at least 6 months were assessed for timed urine levels of pi-GST, THP, HbA1c,
      albumin, and plasma C-reactive protein (CRP). Carotid artery intima-media
      thickness (IMT), brachial artery flow-mediated dilatation (FMD), and cutaneous
      microvascular function were assessed by high-resolution ultrasound and laser
      Doppler, respectively. RESULTS: Two patients had microalbuminuria (> 20 MUg/min),
      and were therefore removed from the study population. pi-GST:crea ratio and
      THP:crea showed no relationship to the demographic, diabetes, or inflammatory
      indices. Lower pi-GST:crea ratio was associated with greater IMT (p = 0.01, r = 
      0.29), particularly in female patients (p = 0.004, r = -0.49). The association of
      pi-GST:crea ratio with IMT was stronger in patients with passive smoke exposure
      (p = 0.002, r = -0.43). Among post-pubertal patients, lower pi-GST:crea ratio was
      also associated with lower microvascular response to Ach (acetylcholine; p =
      0.03, r = 0.49). CONCLUSIONS: In young patients with type1 diabetes, proximal
      tubular dysfunction as suggested by lower levels of pi-GST:crea ratio seems to be
      paralleled by changes in arterial structure and microvascular function.

PMID- 24667018
TI  - Strategies to enhance participant recruitment and retention in research involving
      a community-based population.
AB  - Challenges associated with recruiting and retaining community-based populations
      in research studies have been recognized yet remain of major concern for
      researchers. There is a need for exchange of recruitment and retention techniques
      that inform recruitment and retention strategies. Here, the authors discuss a
      variety of methods that were successful in exceeding target recruitment and
      retention goals in a randomized clinical trial of hearing protector use among
      farm operators. Recruitment and retention strategies were 1) based on a
      philosophy of mutually beneficial engagement in the research process, 2)
      culturally appropriate, 3) tailored to the unique needs of partnering agencies,
      and 4) developed and refined in a cyclical and iterative process. Sponsoring
      organizations are interested in cost-effective recruitment and retention
      strategies, particularly relating to culturally and ethnically diverse groups.
      These approaches may result in enhanced subject recruitment and retention,
      concomitant containment of study costs, and timely accomplishment of study aims. 

PMID- 24667020
TI  - Roles of small RNAs in plant disease resistance.
AB  - The interaction between plants and pathogens represents a dynamic competition
      between a robust immune system and efficient infectious strategies. Plant innate
      immunity is composed of complex and highly regulated molecular networks, which
      can be triggered by the perception of either conserved or race-specific
      pathogenic molecular signatures. Small RNAs are emerging as versatile regulators
      of plant development, growth and response to biotic and abiotic stresses. They
      act in different tiers of plant immunity, including the pathogen-associated
      molecular pattern-triggered and the effector-triggered immunity. On the other
      hand, pathogens have evolved effector molecules to suppress or hijack the host
      small RNA pathways. This leads to an arms race between plants and pathogens at
      the level of small RNA-mediated defense. Here, we review recent advances in small
      RNA-mediated defense responses and discuss the challenging questions in this
      area. 

PMID- 24667019
TI  - Serum uric acid and hypertension in adults: a paradoxical relationship in type 1
      diabetes.
AB  - Adults with type 1 diabetes have lower serum uric acid levels compared with
      nondiabetic adults. Little is known about the relationship between serum uric
      acid and blood pressure in type 1 diabetes and whether it differs from the
      positive relationship found in nondiabetic adults. The authors assessed the cross
      sectional and longitudinal relationships over 6 years between serum uric acid and
      blood pressure in adults with (35+/-9 years [n=393]) and without (38+/-9 years
      [n=685]) type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes
      study. In nondiabetic adults, serum uric acid was associated with systolic blood
      pressure in multivariable models adjusted for cardiovascular risk factors. In
      adults with type 1 diabetes, a negative association was observed between serum
      uric acid and systolic blood pressure after multivariable adjustments. A positive
      association was observed between serum uric acid and systolic blood pressure in
      nondiabetic adults. In contrast, an inverse relationship was demonstrated after
      multivariable adjustments in type 1 diabetes. 

PMID- 24667021
TI  - Very late outcomes for mitral valve replacement with the Carpentier-Edwards
      pericardial bioprosthesis: 25-year follow-up of 450 implantations.
AB  - OBJECTIVE: The aim of the present study was to evaluate the very-long-term
      results of the Carpentier-Edwards pericardial bioprosthesis in the mitral
      position. METHODS: From 1984 to 2011, 450 Carpentier-Edwards PERIMOUNT
      pericardial mitral bioprostheses were implanted in 404 consecutive patients (mean
      age, 68 years; 53% female). Patients undergoing multiple valve replacements were
      excluded. The clinical, operative, and follow-up data were prospectively
      recorded. The mean follow-up was 7.2+/-5.1 years, for a total of 3258 valve
      years. The follow-up data were 97.8% complete. RESULTS: The operative mortality
      rate was 3.3%. A total of 188 late deaths occurred, for a linearized rate of
      5.8%/valve-year. At 20 years, the overall actuarial survival rate was 16.9%+/
      3.9%. Age at implantation, preoperative New York Heart Association class III or
      IV, and redo procedure were significant risk factors affecting late survival. The
      actuarial freedom from complications at 20 years was thromboembolism, 83.9%+/
      7.6%; hemorrhage, 80.2%+/-10.8%; endocarditis, 94.8%+/-1.4%; structural valve
      deterioration, 23.7%+/-6.9%; and explantation owing to structural valve
      deterioration, 40.5%+/-8.0%. The competing risk analysis demonstrated an actual
      risk of explantation owing to structural valve deterioration at 20 years of
      25.5%+/-2.9%. The expected valve durability was 16.6 years for the entire cohort
      (11.4, 16.6, and 19.4 years for patients aged <60, 60 to 70, and >70 years,
      respectively). CONCLUSIONS: With a low rate of valve-related events at 20 years
      and, in particular, a low rate of structural valve deterioration, the Carpentier
      Edwards PERIMOUNT pericardial bioprosthesis remains a reliable choice for a
      mitral tissue valve, especially in patients >60 years old.

PMID- 24667022
TI  - A clinicopathologic prediction model for postoperative recurrence in stage Ia non
      small cell lung cancer.
AB  - OBJECTIVE: Controversy remains over the appropriate postoperative management for
      patients with stage Ia non-small cell lung cancer who underwent complete surgical
      resection as a result of a heterogeneous prognosis. We aimed to identify the
      predictive factors for recurrence in these patients to aid in the decision
      making. METHODS: We reviewed 344 patients with stage Ia non-small cell lung
      cancer to analyze the associations between recurrence-free survival and the
      following clinicopathologic variables: age, gender, smoking history, family
      history, preoperative serum carcinoembryonic antigen level, type of surgical
      resection, tumor location, tumor histology, lymphovascular invasion, tumor
      differentiation, and pathologic T status. RESULTS: Cox multivariate survival
      analysis revealed that central tumor location (P=.019), stage T1b (P=.006), high
      histologic grade (including large cell carcinoma, solid predominant,
      micropapillary predominant, and invasive mucinous adenocarcinoma, P=.007), poor
      differentiation (P=.022), and lymphovascular invasion (P=.035) were independently
      associated with recurrence-free survival. A nomogram for predicting the
      probability of 3-year recurrence-free survival was developed using the 5
      variables. This model shows good calibration, reasonable discrimination
      (concordance index=0.733), and small overfitting (2.6%) demonstrated by
      bootstrapping. CONCLUSIONS: We developed a clinicopathologic prediction model for
      postoperative recurrence in stage Ia non-small cell lung cancer. This model can
      help with the selection of appropriate postoperative therapeutic strategies for
      these patients.

PMID- 24667023
TI  - Discussion.

PMID- 24667024
TI  - Event recorder monitoring to compare the efficacy of a left versus biatrial
      lesion set in patients undergoing concomitant surgical ablation for atrial
      fibrillation.
AB  - OBJECTIVES: Various lesion sets and subsequent success rates have been reported
      in patients receiving concomitant surgical ablation for atrial fibrillation.
      However, most of these results have been obtained by discontinuous monitoring. We
      report results using continuous event recorder rhythm monitoring to compare more
      accurately the efficacy of a left versus biatrial lesion set to treat patients
      with persistent atrial fibrillation. METHODS: Between July 2008 and December
      2011, 66 patients with persistent or long-standing persistent atrial fibrillation
      underwent concomitant surgical atrial fibrillation ablation with a biatrial
      lesion set and subcutaneous event recorder implantation. The results and outcomes
      were compared with a propensity score-matched cohort of 66 patients with a left
      atrial lesion set and event recorder implantation. Event recorder interrogation
      was performed at 3, 6, and 12 months follow-up. RESULTS: The mean patient age was
      70.2+/-7.4 years, and 70.3% were male. No major ablation-related complications
      occurred. One-year survival was 94.8% with no statistically significant
      differences between the 2 groups. The overall rate of freedom from atrial
      fibrillation was 57.3% and 64.4% after 3 and 12 months follow-up, respectively.
      Three months postoperatively, patients in the biatrial group had a slightly
      higher rate of freedom from atrial fibrillation (63.6% vs 52.3% P=.22), but it
      did not reach statistical significance. At 12 months follow-up, a statistically
      significant higher rate of freedom from atrial fibrillation was observed in
      patients with a biatrial lesion set (74.4% vs 55.8%; P=.026). The mean atrial
      fibrillation burden in all patients was 15.1%+/-12.5% in the biatrial group and
      21.2%+/-14.4% in the left atrial group 12 months postoperatively (P=.03).
      CONCLUSIONS: Continuous rhythm monitoring by subcutaneous event recorder
      implantation was safe and feasible. In patients undergoing biatrial ablation, a
      statistically significant higher rate of freedom from atrial fibrillation was
      observed at 12 months follow-up.

PMID- 24667025
TI  - A simple surgical technique for closure of apical muscular ventricular septal
      defect.
AB  - OBJECTIVE: Ventricular septal defect (VSD) is among the most common congenital
      heart diseases encountered in pediatric cardiac patients. Apical muscular VSD
      constitutes nearly 2% of defects, which may or may not be associated with other
      congenital heart defects. The purpose of our study is to present our innovative
      and simple surgical technique using custom-made low-profile
      polytetrafluoroethylene (PTFE) single disc device for closing multiple apical
      muscular and isolated apical muscular VSD. METHOD: Between January 2010 and July
      2013, 17 patients with isolated or multiple apical muscular VSDs with or without
      associated heart diseases underwent operation at our institute. The apical VSD
      was closed using our custom-made low-profile single disc polytetrafluoroethylene
      device. The operative technique and the technique used to prepare the single disc
      device are detailed. RESULTS: Seventeen patients of ages ranging from 3 months to
      7 years underwent operation over 3 years. One 8-month-old patient with
      transposition of the great arteries with multiple VSDs died after 35 days due to
      severe pulmonary artery hypertension and sepsis. Another newborn infant with
      infracardiac total anomalous pulmonary venous connection with a 4-mm apical VSD
      also died after 3 days because this VSD could not be identified. All other
      patients are doing well on follow-up. CONCLUSIONS: The technique described by us
      has the advantage of apical VSD closure through the left ventricle without left
      ventriculotomy. Our technique is simple and cost-effective.

PMID- 24667026
TI  - Improving interstage survival after Norwood operation: outcomes from 10 years of
      home monitoring.
AB  - OBJECTIVE: Infants who undergo Norwood stage 1 palliation (S1P) continue with
      high-risk circulation until stage 2 palliation (S2P). Routine care during the
      interstage period is associated with 10% to 20% mortality. This report
      illustrates the sustained reduction of interstage mortality over 10 years
      associated with use of home monitoring. METHODS: Daily monitoring of oxygen
      saturation and weight was done for all patients discharged to home after S1P.
      Notification of the care team occurred for oxygen saturation<75% or >90%, weight
      gain<20 g over 3 days, weight loss>30 g, or intake<100 cc/kg/d. Breach of these
      criteria marked an interstage event. Interstage outcomes are reported. Patient
      characteristics and perioperative variables were compared between patients with
      and without interstage events. RESULTS: Over 10 years, 157 patients were
      discharged after S1P with home monitoring. Interstage survival was 98%. Breach of
      home criteria occurred in 59% (93 out of 157), with violation of oxygen
      saturation<75% the most common event. Patient characteristics, operative data,
      and early postoperative morbidity did not differ between patients with and
      without events. CONCLUSIONS: Home monitoring after S1P is associated with
      excellent interstage survival. Although a breach of monitoring criteria occurred
      in more than half of patients, our analysis failed to identify independent
      predictors of interstage events. Analysis of variables predicting mortality could
      not be assessed due to the low frequency of death in this cohort. Failure to
      identify specific variables for interstage events suggests that home monitoring,
      as part of an interstage surveillance program, should be applied to all S1P
      hospital survivors.

PMID- 24667027
TI  - Continuative statin therapy after percutaneous coronary intervention improves
      outcome in coronary bypass surgery: a propensity score analysis of 2501 patients.
AB  - OBJECTIVES: A history of percutaneous coronary intervention increases the risk of
      death and complications of coronary artery bypass grafting. This retrospective
      multicenter study evaluated the impact of continuative use of statin on
      postoperative outcomes when subsequent elective coronary artery bypass grafting
      is required after percutaneous coronary intervention. METHODS: Among 14,575
      patients who underwent isolated first-time coronary artery bypass grafting
      between January 2000 and December 2010, 2501 who had previous percutaneous
      coronary intervention with stenting and fulfilled inclusion criteria were
      enrolled. Continuative statin therapy was used in 1528 patients and not used in
      973 patients. Logistic multiple regression and propensity score analyses were
      used to assess the risk-adjusted impact of statin therapy on in-hospital
      mortality and major adverse cardiac events. The Cox proportional hazards model
      was constructed to assess the effect of continuative statin therapy on 24-month
      outcome. RESULTS: At multivariate analysis, age more than 70 years, 3-vessel or 2
      vessel plus left main coronary disease, multivessel percutaneous coronary
      intervention, ejection fraction 0.40 or less, diabetes mellitus, and logistic
      European System for Cardiac Operative Risk Evaluation 5 or greater were
      independent predictors of hospital mortality and major adverse cardiac events.
      After propensity score matching, conditional logistic regression analysis
      demonstrated that continuative statin therapy before coronary artery bypass
      grafting reduced the risk for hospital and 2-year mortality (odds ratio [OR],
      0.27; 95% confidence interval [CI], 0.12-0. 57; P=.004 and OR, 0.6; 95% CI, 0.36
      0.96; P=.04, respectively) and major adverse cardiac events (OR, 0.31; 95% CI,
      0.18-0.78; P=.003 and OR, 0.5; 95% CI, 0.34-0.76; P=.006, respectively).
      CONCLUSIONS: Long-term statin treatment after percutaneous coronary intervention
      improves early and midterm outcome when surgical revascularization will be
      required.

PMID- 24667028
TI  - Valve-sparing aortic root replacement and remodeling with complex aortic valve
      reconstruction in children and young adults with moderate or severe aortic
      regurgitation.
AB  - OBJECTIVES: The durability of valve-sparing aortic root procedures with aortic
      regurgitation due to leaflet disease is questioned. Here, we review our
      experience in combined aortic root and valve reconstruction in children and young
      adults. METHODS: All valve-sparing aortic root procedures from 2000 to 2012 were
      reviewed, and patients with aortic valve repair beyond resuspension were
      included. Root procedures were classified as replacement with reimplantation,
      root remodeling, or aortic annular and sinotubular junction stabilization. The
      primary end point was structural valve deterioration, a composite of aortic valve
      reoperation and/or moderate or greater regurgitation at follow-up. RESULTS:
      Thirty-four patients were included during the study period. The surgery consisted
      of reimplantation in 13 patients, remodeling in 16 patients, and annular and
      sinotubular junction stabilization in 5 patients. Valve repair consisted of
      leaflet procedures in 26 patients and subannular reduction in 15 patients. During
      a median follow-up of 4.2 months (range, 2 weeks-8 years), there were 5
      reoperations for aortic valve replacement due to aortic regurgitation, and 2
      patients presented with moderate or greater regurgitation. Freedom from
      structural valve deterioration was 70.1% +/- 10.3% at 1 year and remained stable
      thereafter, although it was significantly worse in the reimplantation group (P =
      .039). A more severe degree of preoperative aortic regurgitation (P = .001) and
      smaller graft to aortic annulus ratio (P = .003) were predictors of structural
      valve deterioration. CONCLUSIONS: Valve-sparing root and valve reconstruction can
      be done with low operative risk and allows valve preservation in most patients.
      These data should question the assumption that reimplantation is superior when
      associated with complex valve reconstruction.

PMID- 24667029
TI  - A standardized repair-oriented strategy for mitral insufficiency in infants and
      children: midterm functional outcomes and predictors of adverse events.
AB  - OBJECTIVE: Surgical management of mitral regurgitation (MR) in children remains a
      challenge because of the heterogeneity of the anatomy, growth potential, and
      necessity to avoid valve replacement. Our objective was to assess the functional
      outcomes and prognostic factors of a standardized strategy of mitral valve (MV)
      repair for children with MR. METHODS: Consecutive patients aged <18 years who had
      undergone surgery for severe MR from 2001 to 2012 were studied retrospectively.
      The standardized repair strategy mainly included leaflet debridement,
      annuloplasty, and leaflet augmentation. Multivariable risk analyses for recurrent
      MR (grade>II), transmitral mean echocardiographic gradient>5 mm Hg, MV
      reoperation, replacement, and mortality were performed. RESULTS: A total of 106
      patients were included (median age, 5.1 years; range, 11 days to 18 years). The
      mean follow-up period was 3.9+/-3.2 years (range, 2 months to 11 years). The
      proportion of congenital and left heart obstruction-related (left ventricular
      outflow tract obstruction) etiology was 49% (n=52) and 11% (n=12), respectively.
      MV repair was performed primarily in 97% of the patients. The mortality,
      reoperation, replacement, and MR rate at the last follow-up visit was 4.5% (n=5),
      23% (n=24), 5.5% (n=6), and 17% (n=18), respectively. Actuarial survival was
      93%+/-2% at 10 years. Freedom from MV replacement was 95%+/-2% and 86%+/-7% at 5
      and 15 years, respectively. Native valve preservation was obtained in 85% of the
      infants and 94% beyond infancy. Independent predictors of recurrent MR, MV
      reoperation, and replacement included left ventricular outflow tract obstruction
      etiology (hazard ratio, 45; P=.004), associated preoperative mitral stenosis
      (hazard ratio, 21; P=.03), and young age (hazard ratio, 1.2; P=.04). CONCLUSIONS:
      A standardized and reproducible MV repair strategy can achieve satisfactory
      functional results in infants and children with severe MR, allowing native valve
      preservation. The left ventricular outflow tract obstruction-related etiology was
      the main independent predictor of recurrent MR, MV reoperation, and MV
      replacement.

PMID- 24667030
TI  - Schistosoma haematobium hotspots in south Nyanza, western Kenya: prevalence,
      distribution and co-endemicity with Schistosoma mansoni and soil-transmitted
      helminths.
AB  - BACKGROUND: Schistosomiasis studies in western Kenya have mainly focused on the
      intestinal form, with evidence of urinary schistosomiasis remaining anecdotal.
      Detailed disease mapping has been carried out predominantly along the shores of
      Lake Victoria, but there is a paucity of information on intestinal and urinary
      schistosomiasis in inland sites. METHODS: This cross-sectional survey of 3,487
      children aged 7-18 years from 95 schools in south Nyanza, western Kenya
      determined the prevalence, infection intensity, and geographical distribution of
      Schistosoma haematobium, evaluating its co-endemicity with Schistosoma mansoni
      and soil-transmitted helminths (STHs). Helminth eggs were analyzed from single
      urine (for S. haematobium) and stool (for S. mansoni and STHs) samples by
      centrifugation and Kato-Katz, respectively. Hematuria was used as a proxy
      indicator for S. haematobium. Schools and water bodies (ponds, water-points,
      streams, dams and rivers) were mapped using Geographical Information System and
      prevalence maps obtained using ArcView GIS Software. RESULTS: S. haematobium
      infections with an overall prevalence of 9.3% (95% CI = 8.4-10.2%) were mostly
      prevalent in Rachuonyo, 22.4% (95% CI = 19.2-25.9% and 19.7 eggs/10 ml) and
      Migori, 10.7% (95% CI = 9.2-12.3% and 29.5 eggs/10 ml) districts, particularly
      around Kayuka pond and Ongoche river respectively. Overall infections correlated
      with hematuria (r = 0.9, P < 0.0001) and were more likely in boys (P < 0.0001, OR
      = 0.624). S. mansoni infections with an overall prevalence of 13% (95% CI =11.9
      14.1%) were majorly confined along the shores of Lake Victoria. STH infections
      were homogenously distributed with A. lumbricoides occurring in 5.4% (95% CI =
      4.7-6.3%) and T. trichiura in 2.8% (95% CI = 2.3-3.4%) of the children. Although
      S. mansoni infections were more co-endemic with S. haematobium, only A.
      lumbricoides infections were positively associated with S. haematobium (P =
      0.0295, OR = 0.4585). Overall prevalence of S. haematobium monoinfection was 7.2%
      (95% CI = 6.4-8%), S. mansoni monoinfection was 12.3% (95% CI = 10.4-12.5%), and
      S. haematobium-S. mansoni coinfection was 1.2% (95% CI = 0.9-1.6%). There was no
      significant difference in infection intensity between mono and coinfections.
      CONCLUSION: Prevalence distribution maps obtained are important for planning and
      implementing disease control programs in these areas.

PMID- 24667031
TI  - Intravenous ferric carboxymaltose for anaemia in pregnancy.
AB  - BACKGROUND: Iron deficiency is a common nutritional deficiency amongst women of
      childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with
      significant maternal, fetal and infant morbidity. Current options for treatment
      are limited: these include oral iron supplementation, which can be ineffective
      and poorly tolerated, and red blood cell transfusions, which carry an inherent
      risk and should be avoided. Ferric carboxymaltose is a new treatment option that
      may be better tolerated.The study was designed to assess the safety and efficacy
      of iron deficiency anaemia (IDA) correction with intravenous ferric
      carboxymaltose in pregnant women with mild, moderate and severe anaemia in the
      second and third trimester. METHODS: Prospective observational study; 65 anaemic
      pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40
      weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment
      effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient
      report of well-being in the postpartum period. Safety was assessed by analysis of
      adverse drug reactions and fetal heart rate monitoring during the infusion.
      RESULTS: Intravenous ferric carboxymaltose infusion significantly increased Hb
      values (p < 0.01) above baseline levels in all women. Increased Hb values were
      observed at 3 and 6 weeks post infusion and up to 8 weeks post-infusion. Ferritin
      values increased significantly after the infusion. Only 4 women had repeat
      ferritin values post-partum which remained above baseline levels. Fetal heart
      rate monitoring did not indicate a drug related negative impact on the fetus. Of
      the 29 (44.6%) women interviewed, 19 (65.5%) women reported an improvement in
      their well-being and 9 (31%) felt no different after the infusion. None of the
      women felt worse. No serious adverse effects were found and minor side effects
      occurred in 13 (20%) patients. CONCLUSIONS: Our prospective data is consistent
      with existing observational reports of the safe and effective use of ferric
      carboxymaltose in the treatment of iron deficiency anaemia in pregnancy.

PMID- 24667032
TI  - Cys327Cys polymorphism of the PAPP-A gene (pregnancy associated plasma protein A)
      is related to mortality of long term hemodialysis patients.
AB  - OBJECTIVES: PAPP-A is an independent mortality predictor of long term
      hemodialysis patients and a prognostic marker of acute coronary syndrome in
      general population. Cys327Cys PAPP-A polymorphism (SNP) (rs12375498) was found to
      be of significance in preeclampsia and the C allele of the PAPP-A C/G SNP
      (rs13290387) was defined as an independent risk factor for acute myocardial
      infarction. The aim of the study was to test the role of these PAPP-A SNPs in
      long term hemodialysis patients. DESIGN AND METHODS: The studied group consisted
      of 464 subjects - 319 long term hemodialysis patients (183 men, 136 women, 62+/
      14years) and 145 controls (65 men, 80 women, 49+/-14years). A subgroup of 211
      hemodialysis patients (118 men, 93 women, 63+/-13years) was prospectively
      followed up for 4.5years. During the follow up, 111 patients died, 51 of them due
      to cardiovascular events. PAPP-A SNPs were analyzed by DNA sequencing and serum
      PAPP-A was measured by TRACE. RESULTS: Both SNPs were in Hardy-Weinberg
      equilibrium. Allelic and genotype frequencies did not differ between patients and
      controls and were not related to serum PAPP-A concentrations. Cys327Cys SNP was
      significant for patients' survival (HR (95% CI): 1.616 (1.110-2.353), nominal
      p=0.012, corrected p=0.036) while C/G SNP was not. CONCLUSIONS: Our study shows
      for the first time the significance of Cys327Cys PAPP-A SNP (rs12375498) for
      overall mortality of long term hemodialysis patients. Although it does not
      influence the concentration of PAPP-A it still could affect the correct function
      of this enzyme which has to be clarified in further studies.

PMID- 24667033
TI  - Disaster Research and Evaluation Frameworks.

PMID- 24667034
TI  - p19INK4d is involved in the cellular senescence mechanism contributing to
      heterochromatin formation.
AB  - BACKGROUND: During evolution, organisms with renewable tissues have developed
      mechanisms to prevent tumorigenesis, including cellular senescence and apoptosis.
      Cellular senescence is characterized by a permanent cell cycle arrest triggered
      by both endogenous stress and exogenous stress. The p19INK4d, a member of the
      family of cyclin-dependent kinase inhibitors (INK4), plays an important role on
      cell cycle regulation and in the cellular DNA damage response. We hypothesize
      that p19INK4d is a potential factor involved in the onset and/or maintenance of
      the senescent state. METHODS: Senescence was confirmed by measuring the cell
      cycle arrest and the senescence-associated beta-galactosidase activity. Changes
      in p19INK4d expression and localization during senescence were determined by
      Western blot and immunofluorescence assays. Chromatin condensation was measured
      by microccocal nuclease digestion and histone salt extraction. RESULTS: The data
      presented here show for the first time that p19INK4d expression is up-regulated
      by different types of senescence. Changes in senescence-associated hallmarks were
      driven by modulation of p19 expression indicating a direct link between p19INK4d
      induction and the establishment of cellular senescence. Following a senescence
      stimulus, p19INK4d translocates to the nucleus and tightly associates with
      chromatin. Moreover, reduced levels of p19INK4d impair senescence-related global
      genomic heterochromatinization. Analysis of p19INK4d mRNA and protein levels in
      tissues from differently aged mice revealed an up-regulation of p19INK4d that
      correlates with age. CONCLUSION: We propose that p19INK4d participates in the
      cellular mechanisms that trigger senescence by contributing to chromatin
      compaction. GENERAL SIGNIFICANCE: This study provides novel insights into the
      dynamics process of cellular senescence, a central tumor suppressive mechanism.

PMID- 24667036
TI  - Characterization of Liver-Specific Functions of Human Fetal Hepatocytes in
      Culture.
AB  - This study was designed to assess liver-specific functions of human fetal liver
      cells proposed as a potential source for hepatocyte transplantation. Fetal liver
      cells were isolated from livers of different gestational ages (16-22 weeks), and
      the functions of cell preparations were evaluated by establishing primary
      cultures. We observed that 20- to 22-week-gestation fetal liver cell cultures
      contained a predominance of cells with hepatocytic traits that did not divide in
      vitro but were functionally competent. Fetal hepatocytes performed liver-specific
      functions at levels comparable to those of their adult counterpart. Moreover,
      exposure to dexamethasone in combination with oncostatin M promptly induced
      further maturation of the cells through the acquisition of additional functions
      (i.e., ability to store glycogen and uptake of indocyanine green). In some cases,
      particularly in cultures obtained from fetuses of earlier gestational ages (16-18
      weeks gestation), cells with mature hepatocytic traits proved to be sporadic, and
      the primary cultures were mainly populated by clusters of proliferating cells.
      Consequently, the values of liver-specific functions detected in these cultures
      were low. We observed that a low cell density culture system rapidly prompted
      loss of the mature hepatocytic phenotype with downregulations of all the liver
      specific functions. We found that human fetal liver cells can be cryopreserved
      without significant loss of viability and function and evaluated up to 1 year in
      storage in liquid nitrogen. They might, therefore, be suitable for cell banking
      and allow for the transplantation of large numbers of cells, thus improving
      clinical outcomes. Overall, our results indicate that fetal hepatocytes could be
      used as a cell source for hepatocyte transplantation. Fetal liver cells have been
      used so far to treat end-stage liver disease. Additional studies are needed to
      include these cells in cell-based therapies aimed to treat liver failure and
      inborn errors of metabolism. 

PMID- 24667035
TI  - Launching a salt substitute to reduce blood pressure at the population level: a
      cluster randomized stepped wedge trial in Peru.
AB  - BACKGROUND: Controlling hypertension rates and maintaining normal blood pressure,
      particularly in resource-constrained settings, represent ongoing challenges of
      effective and affordable implementation in health care. One of the strategies
      being largely advocated to improve high blood pressure calls for salt reduction
      strategies. This study aims to estimate the impact of a population-level
      intervention based on sodium reduction and potassium increase - in practice,
      introducing a low-sodium, high-potassium salt substitute - on adult blood
      pressure levels. METHODS/DESIGN: The proposed implementation research study
      includes two components: Phase 1, an exploratory component, and Phase 2, an
      intervention component. The exploratory component involves a triangle taste test
      and a formative research study designed to gain an understanding of the best
      implementation methods. Phase 2 involves a pragmatic stepped wedge trial design
      where the intervention will be progressively implemented in several clusters
      starting the intervention randomly at different times. In addition, we will
      evaluate the implementation strategy using a cost-effectiveness analysis.
      DISCUSSION: This is the first project in a Latin-American setting to implement a
      salt substitution intervention at the population level to tackle high blood
      pressure. Data generated and lessons learnt from this study will provide a strong
      platform to address potential interventions applicable to other similar low- and
      middle-income settings. TRIAL REGISTRATION: This study is registered in
      ClinicalTrials.gov NCT01960972.

PMID- 24667038
TI  - Randomized, contralateral eye study to evaluate the effect of standard and
      inverted side-cut angle on corneal biomechanical properties during femtosecond
      laser-assisted in situ keratomileusis.
AB  - PURPOSE: To evaluate the effect of side-cut angle profile on corneal
      biomechanical properties after femtosecond laser in situ keratomileusis (FS
      LASIK). METHODS: Ninety-six myopic eyes of 48 patients underwent FS-LASIK. One
      eye of each patient was randomized to flap creation with a side-cut angle of 115
      degrees . The fellow eye flap side-cut angle was adjusted to 70 degrees . Mean
      absolute error of flap diameter and mean change in Goldmann-correlated intra
      ocular pressure (IOPg), corneal-compensated IOP (IOPcc), corneal hysteresis (CH),
      corneal resistance factor (CRF), p1 area, p2 area, p1 area 1 and p2 area 1 were
      compared between both groups. RESULTS: Overall, the mean IOPg and CRF showed
      significant reduction at the end of 1 and 3 months, as well as between 1 and 3
      months postoperatively (p <= 0.03). The mean IOPcc and CH showed significant
      reduction (p < 0.001) at the end of 3 months postoperatively. The parameters p1
      area, p2 area, p1 area 1 and p2 area 1 changed significantly at the end of 1 and
      3 months postoperatively (p < 0.001). There was no significant difference between
      both groups with regards to the mean change of IOPg, IOPcc, CH, CRF, p1 area, and
      p1 area 1. In 115 degrees  group, the mean absolute error in flap diameter was
      greater compared with 70 degrees  group (p = 0.014). CONCLUSIONS: The stability
      of IOP and corneal biomechanical properties were not enhanced in FS-LASIK flaps
      with an inverted side-cut angle. The size of corneal flap created with 70 degrees
      side-cut angle was more accurate compared with 115 degrees  side-cut angle.

PMID- 24667039
TI  - Catheter-directed thrombolysis-assisted angioplasty for chronic lower limb
      ischemia.
AB  - BACKGROUND: Thrombolysis is an appropriate treatment for acute arterial
      occlusion. There remains controversy as to whether thrombolysis before
      angioplasty helps to identify the underlying lesion and improve results for
      chronic ischemia of the lower extremity. We sought to investigate the feasibility
      of catheter-directed thrombolysis-assisted angioplasty for chronic lower limb
      ischemia. METHODS: Between July 2008 and December 2009, the data of patients with
      chronic lower limb ischemia undergoing catheter-directed thrombolysis-assisted
      angioplasty were retrospectively analyzed. RESULTS: Twenty consecutive patients
      (18 men with a mean age of 56.35 +/- 8.5 years) underwent thrombolysis-assisted
      angioplasty for occlusion of a native artery (n = 18) or bypass graft (n = 2).
      The median duration of symptoms was 19 months (range: 3-48 months). Symptoms
      included disabling claudication in 12 patients, rest pain in 5 patients, and
      gangrene of the toes in 3 patients. Urokinase or recombinant tissue plasminogen
      activator as a thrombolytic agent was used before angioplasty. The mean length of
      occlusive lesions decreased significantly from 150 mm to 30 mm after thrombolysis
      (P < 0.01). Four patients had no change in their lesions. Improvement of Inter
      Society Consensus for the Management of Peripheral Arterial Disease (TASC II)
      classification was achieved in 16 patients, with 14 TASC IIA lesions and 2 TASC
      IIB lesions after thrombolysis. Subsequent stenting was successfully performed in
      all patients. The ankle-brachial index increased significantly from 0.33 to 0.63
      (P < 0.01). No perioperative deaths occurred. Morbidity included access site
      bleeding in 1 patient and distal embolization in 2 patients without further
      intervention. The primary patency rate at 1 year was 95%, with a median follow-up
      time of 19 months. CONCLUSIONS: Catheter-directed thrombolysis-assisted
      angioplasty is a safe and effective treatment in some patients with chronic lower
      limb ischemia. It may reduce the magnitude of the lesion and simplify the
      expected intervention procedures.

PMID- 24667037
TI  - Ethnic differences and predictors of colonoscopy, prostate-specific antigen, and
      mammography screening participation in the multiethnic cohort.
AB  - PURPOSE: Given the relation between screening and improved cancer outcomes and
      the persistence of ethnic disparities in cancer mortality, we explored ethnic
      differences in colonoscopy, prostate-specific antigen (PSA), and mammography
      screening in the Multiethnic Cohort Study. METHODS: Logistic regression was
      applied to examine the influence of ethnicity as well as demographics, lifestyle
      factors, comorbidities, family history of cancer, and previous screening history
      on self-reported screening participation collected in 1999-2002. RESULTS: The
      analysis included 140,398 participants who identified as white, African American,
      Native Hawaiian, Japanese American, US born-Latino, or Mexican born-Latino. The
      screening prevalences overall were mammography: 88% of women, PSA: 45% of men,
      and colonoscopy: 35% of men and women. All minority groups reported 10-40% lower
      screening utilization than whites, but Mexican-born Latinos and Native Hawaiian
      were lowest. Men were nearly twice as likely to have a colonoscopy (OR=1.94, 95%
      CI=1.89-1.99) as women. A personal screening history, presence of comorbidities,
      and family history of cancer predicted higher screening utilization across
      modalities, but to different degrees across ethnic groups. CONCLUSIONS: This
      study confirms previously reported sex differences in colorectal cancer screening
      and ethnic disparities in screening participation. The findings suggest it may be
      useful to include personal screening history and family history of cancer into
      counseling patients about screening participation.

PMID- 24667041
TI  - MDCT of renal trauma: correlation to AAST organ injury scale.
AB  - Renal injuries affect 8-10% of patients presenting with blunt abdominal trauma.
      Imaging with multidetector computed tomography (MDCT) is the preferred modality
      at most trauma centers. Renal injuries have been categorized by several grading
      schemes in the literature. The classification proposed by the American
      Association for the Surgery of Trauma (AAST) predicts clinical outcome with
      reasonable accuracy. Although the AAST classification for renal injury is
      primarily based on findings during surgery, it has a strong correlation with MDCT
      findings. 

PMID- 24667042
TI  - Clunealgia: CT-guided therapeutic posterior femoral cutaneous nerve block.
AB  - Clunealgia is caused by neuropathy of inferior cluneal branches of the posterior
      femoral cutaneous nerve resulting in pain in the inferior gluteal region. Image
      guided anesthetic nerve injections are a viable and safe therapeutic option in
      sensory peripheral neuropathies that provides significant pain relief when
      conservative therapy fails and surgery is not desired or contemplated. The
      authors describe two cases of clunealgia, where computed-tomography-guided
      technique for nerve blocks of the posterior femoral cutaneous nerve and its
      branches was used as a cheaper, more convenient, and faster alternative with
      similar face validity as the previously described magnetic-resonance-guided
      injection. 

PMID- 24667043
TI  - Interobserver agreement between radiologists and radiology residents and
      emergency physicians in the detection of PE using CTPA.
AB  - OBJECTIVE: To assess interobserver agreement between thoracic radiologists,
      radiology residents, and emergency physicians in diagnosing pulmonary embolism
      (PE). MATERIALS AND METHODS: Emergency physicians, radiology residents, and
      thoracic radiologists evaluated 123 computed tomography pulmonary angiography
      images. Interobserver agreement was analysed using kappa statistics. RESULTS:
      Very good agreements were observed between thoracic radiologists and radiology
      residents (0.81 and 0.82). Fair and moderate agreements (0.39 and 0.42) were
      demonstrated between emergency physicians and thoracic radiologists. CONCLUSIONS:
      Important differences in interobserver agreement were found, with emergency
      physicians tending to overdiagnose PE.

PMID- 24667044
TI  - Intramedullary spinal cord and leptomeningeal metastases from intracranial low
      grade oligodendroglioma.
AB  - We present an unusual case of a patient with an intracranial low-grade
      oligodendroglioma who developed recurrence with an intramedullary spinal cord
      metastasis and multiple spinal leptomeningeal metastases. The intramedullary
      spinal cord metastasis showed mild enhancement similar to the original
      intracranial primary, while the multiple spinal leptomeningeal metastases
      revealed no enhancement. This is the seventh reported case of symptomatic
      intramedullary spinal cord metastasis from a low-grade oligodendroglioma. 

PMID- 24667045
TI  - Clustered pulmonary sclerosing pneumocytoma in a young man: a case report.
AB  - Pulmonary sclerosing pneumocytoma is a rare, benign lung tumor that usually
      occurs in middle-aged women. It usually manifests as isolated pulmonary nodules
      and is often confused with other solitary, benign nodules. We present a case of
      sclerosing pneumocytoma with clustered lung nodules and surrounding ground-glass
      opacity in a single lobe in a young man. Progressive growth was seen on serial
      computed tomography observations, and the nodules appeared similar to those seen
      in active pulmonary tuberculosis. 

PMID- 24667046
TI  - Unusual splenic hemangioma of a pediatric patient: hypointense on T2-weighted
      image.
AB  - Splenic hemangioma is a very rare neoplasm in children. On magnetic resonance
      imaging, splenic hemangioma shows high signal intensity on T2-weighted images. In
      this report, we present the first pediatric case of a splenic hemangioma, which
      was significantly hypointense on T2-weighted images. 

PMID- 24667047
TI  - Chemical-shift MRI of rebound thymic hyperplasia with unusual appearance and
      intense (18)F-FDG uptake in adulthood: report of two cases.
AB  - Rebound thymic hyperplasia (RTH) with increased (18)F-FGD uptake at positron
      emission tomography (PET) computed tomography (CT) is typical of pediatric
      patients after chemotherapy, although it may occasionally occur in adults. At CT,
      RTH usually appears as a diffusely enlarged thymus with areas of fatty
      attenuation. We report two cases of RTH in adults detected at follow-up: both
      showed unusual morphology on CT and were confirmed at PET-CT as areas of strongly
      increased radiopharmaceutical uptake, which suggested disease recurrence.
      Chemical-shift magnetic resonance imaging, however, demonstrated fat infiltration
      within the tissue. Such finding was consistent with the diagnosis of RTH and was
      paramount in preventing unnecessary invasive procedures or treatments. 

PMID- 24667048
TI  - Evolutionary model of the divergence of enterohemorrhagic Escherichia coli O157
      lineage I/II clades reconstructed from high resolution melting and Shiga-like
      toxin 2 analyses.
AB  - We have studied 167 epidemiologically unlinked strains of enterohemorrhagic
      Escherichia coli O157 (O157) isolated from patients with hemorrhagic colitis
      (HC), 87 strains from patients not with HC and 35 asymptomatic carriers (the not
      HC group), and differentiated these strains into clades using high resolution
      melting analysis. In addition, lineage analysis was carried out using lineage
      specific polymorphism assay-6 and analysis of the distribution of IS629 insertion
      sites was carried out using IS-printing. Most strains were correctly clustered by
      minimum spanning tree analysis, and strains in the major clades showed linkage
      disequilibrium, confirming the clade differentiation in this study. The number of
      O157 strains in the different clades isolated from HC patients and the not HC
      group was significantly different (Chi square test, P<0.05), indicating that
      strains in different clades had different pathogenicities for hemorrhagic
      colitis. Pairwise comparison of the number of strains in different clades
      isolated from HC patients indicated that clade 12 strains were weakly pathogenic
      for HC. Stx2 titers and the number of strains carrying an stx2 gene were
      significantly different for different clades (Kruscal-Wallis test and Chi square
      test, P<0.05). Pairwise comparison of the Stx2 titer and the number of strains
      with an stx2 gene in different clades showed that the weak HC pathogenicity of
      clade 12 strains would be related to the low number of clade 12 strains with an
      stx2 gene and the low Stx2 production in those strains. Interestingly, the Stx2
      titer and the prevalence of strains with an stx2 gene were significantly higher
      among clade 6 and 8 strains compared to clade 7 strains, although clades 6, 7,
      and 8 were all in lineage I/II. These results were discordant with the O157
      evolutionary model, suggesting that insertion of an stx2 gene in lineage I/II
      strains after divergence of each clade. 

PMID- 24667040
TI  - An international effort towards developing standards for best practices in
      analysis, interpretation and reporting of clinical genome sequencing results in
      the CLARITY Challenge.
AB  - BACKGROUND: There is tremendous potential for genome sequencing to improve
      clinical diagnosis and care once it becomes routinely accessible, but this will
      require formalizing research methods into clinical best practices in the areas of
      sequence data generation, analysis, interpretation and reporting. The CLARITY
      Challenge was designed to spur convergence in methods for diagnosing genetic
      disease starting from clinical case history and genome sequencing data. DNA
      samples were obtained from three families with heritable genetic disorders and
      genomic sequence data were donated by sequencing platform vendors. The challenge
      was to analyze and interpret these data with the goals of identifying disease
      causing variants and reporting the findings in a clinically useful format.
      Participating contestant groups were solicited broadly, and an independent panel
      of judges evaluated their performance. RESULTS: A total of 30 international
      groups were engaged. The entries reveal a general convergence of practices on
      most elements of the analysis and interpretation process. However, even given
      this commonality of approach, only two groups identified the consensus candidate
      variants in all disease cases, demonstrating a need for consistent fine-tuning of
      the generally accepted methods. There was greater diversity of the final clinical
      report content and in the patient consenting process, demonstrating that these
      areas require additional exploration and standardization. CONCLUSIONS: The
      CLARITY Challenge provides a comprehensive assessment of current practices for
      using genome sequencing to diagnose and report genetic diseases. There is
      remarkable convergence in bioinformatic techniques, but medical interpretation
      and reporting are areas that require further development by many groups.

PMID- 24667049
TI  - Genetic host specificity of hepatitis E virus.
AB  - Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis
      worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with
      swine being the primary reservoir. The relevance of HEV genetic diversity to host
      adaptation is poorly understood. We employed a Bayesian network (BN) analysis of
      HEV3 and HEV4 to detect epistatic connectivity among protein sites and its
      association with the host specificity in each genotype. The data imply
      coevolution among ~70% of polymorphic sites from all HEV proteins and association
      of numerous coevolving sites with adaptation to swine or humans. BN models for
      individual proteins and domains of the nonstructural polyprotein detected the
      host origin of HEV strains with accuracy of 74-93% and 63-87%, respectively.
      These findings, taken together with lack of phylogenetic association to host,
      suggest that the HEV host specificity is a heritable and convergent phenotypic
      trait achievable through variety of genetic pathways (abundance), and explain a
      broad host range for HEV3 and HEV4. 

PMID- 24667050
TI  - Competition between Plasmodium falciparum strains in clinical infections during
      in vitro culture adaptation.
AB  - We evaluated the dynamics of parasite populations during in vitro culture
      adaptation in 15 mixed Plasmodium falciparum infections, which were collected
      from a hypoendemic area near the China-Myanmar border. Allele types at the msp1
      block 2 in the initial clinical samples and during subsequent culture were
      quantified weekly using a quantitative PCR method. All mixed infections carried
      two allele types based on the msp1 genotyping result. We also genotyped several
      polymorphic sites in the dhfr, dhps and mdr1 genes on day 0 and day 28, which
      showed that most of the common sites analyzed were monomorphic. Two of the three
      clinical samples mixed at dhps 581 remained stable while one changed to wild-type
      during the culture. During in vitro culture, we observed a gradual loss of
      parasite populations with 10 of the 15 mixed infections becoming monoclonal by
      day 28 based on the msp1 allele type. In most cases, the more abundant msp1
      allele types in the clinical blood samples at the beginning of culture became the
      sole or predominant allele types on day 28. These results suggest that some
      parasites may have growth advantages and the loss of parasite populations during
      culture adaptation of mixed infections may lead to biased results when comparing
      the phenotypes such as drug sensitivity of the culture-adapted parasites. 

PMID- 24667052
TI  - Hypertension guidelines in need of guidance.

PMID- 24667051
TI  - There is no correlation between sublineages and drug resistance of Mycobacterium
      tuberculosis Beijing/W lineage clinical isolates in Xinjiang, China.
AB  - The Beijing/W lineage strains are the major prevalent strains in China. The
      prevalence, mortality and drug-resistant rates of tuberculosis in Xinjiang,
      Northwestern China are higher than in other parts of the country. Our previous
      study results showed that the dominant strains of Mycobacterium tuberculosis
      (MTB) were 'Beijing/W lineage' MTB in Xinjiang; those strains had no significant
      correlation with drug resistance. We investigated whether the prevalence of
      'Beijing/W lineage' sublineage strains was associated with drug resistance. We
      collected 478 sputum specimens from patients with pulmonary tuberculosis.
      Beijing/W strains and their sublineages were identified by distinguishing five
      specific large sequence polymorphisms, using polymerase chain reaction. All
      strains were subjected to a drug susceptibility test using the proportion method
      on Lowenstein-Jensen culture medium. In total, 379 clinical isolates of MTB were
      isolated and identified, 57.26% of these isolates were identified as Beijing/W
      strains, of which 11.06% isolates were in sublineage 105, 14.74% isolates in
      sublineage 207, 69.59% isolates in sublineage 181, and 4.61% isolates in
      sublineage 150. None of the isolates was in sublineage 142. Our data showed there
      were four sublineages of Beijing/W isolates in Xinjiang province, China. However,
      there were no correlations between drug resistance and the sublineages of
      Beijing/W strains.

PMID- 24667053
TI  - Unique morphologic and clinical features of liver predominant/primary small cell
      carcinoma--autopsy and biopsy case series.
AB  - Liver predominant small cell carcinoma is rare but often presents as hyperacute
      liver failure with unknown primary and is a medical emergency. We present 2
      autopsy and 7 biopsy cases of liver predominant small cell carcinoma and
      demonstrate that these patients present with liver failure and identifiable
      hepatomegaly but lack discrete lesions on imaging as well as no mass lesions
      identified in other organs including lung. Compared with the multiple nodules of
      metastatic small cell carcinoma in the liver, unique morphologic feature of liver
      predominant/primary small cell carcinoma in autopsy and biopsy specimens was a
      diffuse infiltration of small blue neoplastic cells predominantly in the
      sinusoidal space in the liver parenchyma. Before diagnosing liver
      predominant/primary small cell carcinoma, other infiltrating small blue cell
      neoplasms including lymphoma and peripheral neuroectodermal tumor need to be
      ruled out through immunohistochemistry. We, therefore, demonstrate that liver
      biopsy together with a rapid panel of immunostains is necessary to firmly
      establish a diagnosis of liver predominant small cell carcinoma and allow
      clinicians to immediately implement potentially lifesaving chemotherapy. 

PMID- 24667054
TI  - Large nasopharyngeal inverted papilloma presenting with rustling tinnitus.
AB  - Tinnitus is a common symptom caused by numerous diseases. The etiology is unknown
      in most cases; however, nasopharyngeal lesions may cause a certain tinnitus. We
      herein report a case of nasopharyngeal inverted papilloma which presents with
      rustling tinnitus as the sole initial symptom. The tympanic membrane was intact,
      and results of hearing test and impedance audiometry were normal. However,
      sonotubometry showed a complete blockage of the Eustachian tube. A large tumor
      was found that originated from the choana and occupied the nasopharynx which
      caused a rustling sound when she swallowed or spoke. Tinnitus totally subsided
      after removal of this tumor. To our knowledge, the tumor origin and presenting
      symptom of this case are very rare, and nasopharyngeal examination is required in
      the diagnosis of unknown hearing symptoms. 

PMID- 24667055
TI  - Round window reinforcement for superior semicircular canal dehiscence: a
      retrospective multi-center case series.
AB  - PURPOSE: To evaluate the outcome of round window (RW) tissue reinforcement in the
      management of superior semicircular canal dehiscence (SSCD). MATERIALS AND
      METHODS: Twenty-two patients with confirmed diagnosis of SSCD by clinical
      presentation, imaging, and/or testing were included in the study. Six surgeons at
      four institutions conducted a multicenter chart review of patients treated for
      symptomatic superior canal dehiscence using RW tissue reinforcement or complete
      RW occlusion. A transcanal approach was used to reinforce the RW with various
      types of tissue. Patients completed a novel postoperative survey, grading
      preoperative and postoperative symptom severity. RESULTS: Analysis revealed
      statistically significant improvement in all symptoms with the exception of
      hearing loss in 19 patients who underwent RW reinforcement. In contrast, 2 of 3
      participants who underwent the alternate treatment of RW niche occlusion
      experienced worsened symptoms requiring revision surgery. CONCLUSION: RW tissue
      reinforcement may reduce the symptoms associated with SSCD. The reinforcement
      technique may benefit SSCD patients by reducing the "third window" effect created
      by a dehiscent semicircular canal. Given its low risks compared to middle cranial
      fossa or transmastoid canal occlusion, RW reinforcement may prove to be a
      suitable initial procedure for intractable SSCD. In contrast, complete RW
      occlusion is not advised.

PMID- 24667056
TI  - Necrotizing sialometaplasia of the palatal mucosa in patient with history of
      anorexia: review and case report.
AB  - Necrotizing sialometaplasia is a self-limiting disorder affecting minor salivary
      glands resembling a malignant process both clinically and histopathologically.
      The etiology of this rare inflammatory' disorder is related to an ischemic event.
      Identified risk factors include alcohol abuse, smoking, drugs, denture wearing,
      injury and systemic diseases. Also reported are cases of necrotizing
      sialometaplasia associated with bulimia. This paper identifies the whole body
      incitement among additional risk factors by presenting a case of necrotizing
      sialometaplasia in an 18 year old patient with the history of anorexia nervosa.
      Furthermore it describes the effects of extreme cooling of palatal mucosa with
      ice chips resulting in constriction of blood vessels as the direct cause,
      reinforcing ischemic etiology of necrotizing sialometaplasia.

PMID- 24667057
TI  - A randomized prospective trial of a novel device for measuring perforation size
      during inlay 'butterfly' myringoplasty.
AB  - AIM: This study introduces a new device to facilitate perforation size
      measurement during "butterfly" myringoplasty. The purpose of this study is to
      evaluate the use of 'otological compass' on short-term results of inlay
      cartilaginous 'butterfly' tympanoplasty technique in adult patients. STUDY
      DESIGN: Prospective, randomized, controlled, blinded. PATIENTS AND METHODS: This
      study included 25 patients who underwent inlay cartilage myringoplasty. All
      operations were performed under general anesthesia by the same surgeon with a
      microscope-assisted approach. The patients were divided randomly and
      consecutively into two groups: Group 1 (n=12) had perforation dimensions and
      shape measured using the Otologic Compass (OC) and the control group (n=13) had
      perforation measured by means of a Fisch elevator. The duration of surgery,
      number of trials for correct placement of the cartilage graft, results and
      complications of the surgery were evaluated and compared. RESULTS: The mean
      follow-up duration was 6 months. Groups were similar in terms of age and
      perforation diameters (p>0.05). Average number of cartilage shaping before
      satisfactory graft fitting was significantly fewer in the OC group: 1.1 +/- 0.3
      and 2.2 +/- 0.6 trials for OC and control groups, respectively (p<0.001). Mean
      duration of preparation and satisfactory graft fitting was 9.6 +/- 4.2 minutes in
      the OC group whereas it was 18.1 +/- 5.2 minutes for the control group. Operative
      duration was significantly shorter in the OC group (p<0.001). At the end of the
      follow-up period, successful closure occurred 91.7% and 84.6% patients in the OC
      and control groups, respectively (p>0.05). The mean preoperative to postoperative
      three-tone air-bone gap improved 7.9 dB and 9.0 dB in OC and control groups,
      respectively (p>0.05). CONCLUSION: This study shows that OC presents as a useful
      tool that expedites and refines butterfly myringoplasty procedure. The number of
      cartilage shaping prior to satisfactory graft fitting revealed significantly
      better results: almost all surgeries in the OC group were complete after a single
      cartilage shaping attempt.

PMID- 24667058
TI  - The limitations of computed tomography in adult cochlear implant evaluation.
AB  - OBJECTIVE: To demonstrate the added value of magnetic resonance imaging (MRI)
      over computed tomography (CT) during adult cochlear implant evaluation. PATIENTS:
      Two adult patients are discussed in whom MRI studies diagnosed bilateral
      vestibular schwannomas during cochlear implant candidacy evaluation.
      INTERVENTIONS: Temporal bone CT and MRI. MAIN OUTCOME MEASURE: Diagnosis of NF2.
      RESULTS: Two adult patients, ages 67 and 68 years, were evaluated for cochlear
      implant candidacy. Both patients experienced slowly progressive, bilateral
      hearing loss without complaints of vertigo, and neither patient had a family
      history of hearing loss or neurogenic tumors. Both patients had near-symmetric
      pure tone thresholds on audiometric testing. An MRI and a CT scan were performed
      on both patients, and bilateral vestibular schwannomas were identified on MRI.
      CONCLUSIONS: Though MRI is not routinely utilized in adult cochlear implant
      evaluation, it may be of greater clinical value than CT in the setting of adult
      onset hearing loss. MRI allows for sensitive evaluation of cochlear patency and
      architecture, and cochlear nerve status. As demonstrated in the two index cases,
      MRI also provides the added benefit of evaluating for causes of retrocochlear
      hearing loss. These two patients would have likely experienced a significant
      delay in diagnosis of NF2 without preoperative MRI, particularly given the
      limitations of scanning following CI magnet placement.

PMID- 24667059
TI  - Study of the cytotoxicity of asiaticoside on rats and tumour cells.
AB  - BACKGROUND: Cancer chemoprevention is considered one of the most promising areas
      in current cancer research, and asiaticoside, which is derived from the plant
      Centella asiatica, has a relative lack of systemic toxicity. The purpose of this
      study was to investigate whether asiaticoside is effective against 7,12
      dimethylbenz(a)anthracene (DMBA)-induced carcinogenicity in vitro (MCF-7 and
      other cells) and in vivo (DMBA-induced rat cancer). METHODS: An MTT assay was
      performed involving the treatment of MCF-7 cells for 48 h with H2O2 alone and
      H2O2 + different asiaticoside concentrations. Flow cytometry was performed, and
      the level of caspase 3, tumour necrosis factor-alpha (TNF-alpha) and interleukin
      1 (IL-1) were quantified. Adult female Sprague-Dawley (SD) rats were divided into
      five groups designated I (control), II (DMBA-induced cancer), III (pre- and post
      treatment with asiaticoside (200 MUg/animal) in DMBA-induced cancer), IV (post
      treatment with asiaticoside in DMBA-induced cancer), and V (treated with
      asiaticoside alone, drug control). Twelve weeks post-DMBA, rats developed mammary
      tumours. Rats either were sacrificed or imaged with MIBI. Histological
      examination of tumour tissues was performed. Tumour MIBI uptake ratios were
      determined. The data are expressed as the means +/- standard deviation.
      Appropriate t-test and ANOVA statistical methods were used to compare data.
      RESULTS: The IC50 of asiaticoside for MCF-7 cells was determined to be 40 MUM.
      Asiaticoside has potential for hydrogen peroxide cytotoxicity, and the caspase-3
      activity increased with increasing asiaticoside dose in MCF-7 cells treated for
      48 h. The expression of the cytokines TNF-alpha and IL-1beta was significantly
      decreased and correlated with MIBI uptake ratios in vitro and in vivo after
      asiaticoside administration. CONCLUSION: This study demonstrates that
      asiaticoside is effective in vitro and in vivo in inducing apoptosis and
      enhancing anti-tumour activity.

PMID- 24667060
TI  - PLA2R1: expression and function in cancer.
AB  - The phospholipase A2 receptor 1 (PLA2R1 or PLA2R) was isolated twenty years ago
      for its ability to bind several secretory phospholipase A2 proteins (sPLA2).
      Since its identification, it has attracted only a limited interest, mainly in the
      sPLA2 biology field, as it is viewed uniquely as a regulator of sPLA2 activities.
      Recent discoveries outline novel important functions of this gene in cancer
      biology. Indeed, PLA2R1 gain or loss of function experiments in vitro and in vivo
      shows that this receptor promotes several tumor suppressive responses including
      senescence, apoptosis and inhibition of transformation. Supporting a tumor
      suppressive role of PLA2R1, its expression decreases in numerous cancers, and
      known oncogenes such as HIF2alpha and c-MYC repress its expression. PLA2R1
      promoter methylation, a classical way to repress tumor suppressive gene
      expression in cancer cells, is observed in leukemia, in kidney and in breast
      cancer cells. Mechanistically, PLA2R1 activates the kinase JAK2 and orients its
      activity towards a tumor suppressive one. PLA2R1 also promotes accumulation of
      reactive oxygen species which induce cell death and senescence. This review
      compiles recent data demonstrating an unexpected tumor suppressive role of PLA2R1
      and outlines the future work needed to improve our knowledge of the functions of
      this gene in cancer. 

PMID- 24667061
TI  - A current review of avian influenza in pigeons and doves (Columbidae).
AB  - Recent reports of the detection of the zoonotic low pathogenic avian influenza
      (LPAI) H7N9 viruses in healthy pigeons have again put the spotlight on the
      potential role of pigeons and doves in the transmission of avian influenza
      between infected poultry and humans. A surge in studies followed the highly
      pathogenic avian influenza (HPAI) H5N1 epidemic, and this review collates the new
      data on AIV in pigeons and doves, both from a surveillance perspective, as well
      as the results of numerous clinical studies. Collectively, results of 32 field
      studies representing 24 countries across four continents indicate an antibody
      prevalence of 8.01% in pigeons and doves but only 0.37% of the total was
      associated with exposure to the same serotype as a highly pathogenic avian
      influenza (HPAI) outbreak occurring in poultry at the time. Only 1.1% of 6155
      columbids sampled tested positive for the virus, and only 9/6155 (0.15%) viruses
      were detected in regions that were experiencing outbreaks of a notifiable
      serotype at the time. In 22 experimental infection studies with HPAI and LPAI
      viruses since 1944, only 26/715 (3.64%) mortalities were reported, and these
      could usually be associated with excessive doses of inoculum, which would induce
      fatal inflammatory responses. Since seroconversion and virus detection was
      demonstrated in many of these studies, albeit without clinical signs in most
      cases, it is clear that columbids are susceptible to infection, but ineffective
      propagators and disseminators of the virus, i.e. "dead end" hosts for AIVs, even
      HPAI. Viruses are shed in minute quantities from both the choana and in the feces
      for a short duration but titers are below the minimum threshold require to infect
      other species. 

PMID- 24667062
TI  - First report of a new alphaherpesvirus in a freshwater turtle (Pseudemys concinna
      concinna) kept in Germany.
AB  - Herpesviruses represent important pathogenic agents in zoological chelonian
      collections. Infections in tortoises are actually most commonly associated with
      necrotizing lesions in the upper digestive tract. Herpesvirus infections in sea
      turtles are most commonly associated with fibropapillomatosis, although other
      disease complexes caused by other herpesviruses have been described.
      Herpesviruses are known to cause latent infections and may be reactivated upon
      various endogenous or exogenous stimuli resulting in acute and sometimes fatal
      disease. The present description represents the first report about a new
      alphaherpesvirus found in a fresh water turtle (Pseudemys concinna concinna). The
      animal died suddenly without showing clinical signs. Macroscopically, no lesions
      typically associated with a herpesvirus infection were found. Light microscopic
      examination showed hepatic lipidosis and countless numbers of intranuclear
      inclusion bodies in hepatocytes as the only significant light microscopic lesion.
      Transmission electron microscopy revealed typical herpesvirus particles in the
      nucleus of hepatocytes. To further substantiate these observations a molecular
      identification using PCR followed by sequencing of the obtained fragments was
      performed. Phylogenetic analysis indicated a new alphaherpesvirus called Emydid
      herpesvirus 1. 

PMID- 24667063
TI  - SYRCLE's risk of bias tool for animal studies.
AB  - BACKGROUND: Systematic Reviews (SRs) of experimental animal studies are not yet
      common practice, but awareness of the merits of conducting such SRs is steadily
      increasing. As animal intervention studies differ from randomized clinical trials
      (RCT) in many aspects, the methodology for SRs of clinical trials needs to be
      adapted and optimized for animal intervention studies. The Cochrane Collaboration
      developed a Risk of Bias (RoB) tool to establish consistency and avoid
      discrepancies in assessing the methodological quality of RCTs. A similar
      initiative is warranted in the field of animal experimentation. METHODS: We
      provide an RoB tool for animal intervention studies (SYRCLE's RoB tool). This
      tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias
      that play a specific role in animal intervention studies. To enhance transparency
      and applicability, we formulated signalling questions to facilitate judgment.
      RESULTS: The resulting RoB tool for animal studies contains 10 entries. These
      entries are related to selection bias, performance bias, detection bias,
      attrition bias, reporting bias and other biases. Half these items are in
      agreement with the items in the Cochrane RoB tool. Most of the variations between
      the two tools are due to differences in design between RCTs and animal studies.
      Shortcomings in, or unfamiliarity with, specific aspects of experimental design
      of animal studies compared to clinical studies also play a role. CONCLUSIONS:
      SYRCLE's RoB tool is an adapted version of the Cochrane RoB tool. Widespread
      adoption and implementation of this tool will facilitate and improve critical
      appraisal of evidence from animal studies. This may subsequently enhance the
      efficiency of translating animal research into clinical practice and increase
      awareness of the necessity of improving the methodological quality of animal
      studies.

PMID- 24667064
TI  - Single tube genotyping of TYMS 1494del6 polymorphism in the Chinese Han
      population by duplex scorpion primers.
AB  - BACKGROUND: The development of pharmacogenomics has created an urgent need for
      robust molecular characterization. And it has become a challenge to develop
      suitable detecting methods for routine clinical use. AIM: The aim of the current
      study is to develop a simple and reliable TYMS 1494del6 polymorphism genotyping
      assay by duplex scorpion primers in the Chinese Han population. METHOD: We
      evaluated the performance of the duplex scorpion primer assay in the genotyping
      of TYMS 1494del6 polymorphism and screened 54 DNA samples of the Chinese Han
      population. The results were further validated by pyrosequencing. RESULTS: The
      duplex scorpion primer assay showed high specificity and accuracy for genotyping
      TYMS 1494del6 polymorphism. Complete concordance was observed between the duplex
      scorpion primer assay and pyrosequencing. The frequency of the TYMS +6 bp allele
      was 34% and the -6 bp allele was 66% in 54 Chinese Han population DNA samples.
      CONCLUSION: The duplex scorpion primer assay provides a rapid, reliable and high
      throughput method to genotype TYMS 1494del6 polymorphism in the Chinese Han
      population.

PMID- 24667065
TI  - First report of Babesia gibsoni in Central America and survey for vector-borne
      infections in dogs from Nicaragua.
AB  - BACKGROUND: Although many vector-borne diseases are important causes of morbidity
      and mortality in dogs in tropical areas and potential zoonoses, there is little
      information on these conditions in Central America. METHODS: Seven qPCRs for
      vector-borne pathogens were performed on a Roche LightCycler PCR Instrument to
      investigate their prevalence in a convenience sample of whole blood samples from
      apparently healthy dogs in Nicaragua. Also, a qPCR targeting the canine
      hydroxymethylbilane synthase (HMBS) gene was used as an endogenous internal
      control and verified the quality and quantity of DNA in the samples was
      appropriate for the study. RESULTS: We found DNA of Rickettsia felis (5%),
      Babesia spp. (26%), Hepatozoon canis (51%), Anaplasma platys (13%) and Ehrlichia
      canis (56%) in the 39 dogs studied. The qPCRs for Coxiella burnetii and
      Dirofilaria immitis were negative. Of the 30 (80%) dogs that were positive by
      qPCR, 12 (31%) were positive for one agent, 11 (28%) for two, 3 (8%) for three,
      and 4 (10%) for four agents. CONCLUSIONS: This is the first report of B. gibsoni
      in dogs from Central America and the first recording of vector-borne agents in
      dogs from Nicaragua. Dogs in Nicaragua are commonly infected with a variety of
      vector-borne pathogens, some of which may also infect people.

PMID- 24667066
TI  - Thickness variations and absence of lateral compositional fluctuations in
      aberration-corrected STEM images of InGaN LED active regions at low dose.
AB  - Aberration-corrected scanning transmission electron microscopy images of the
      In(0.15)Ga(0.85)N active region of a blue light-emitting diode, acquired at ~0.1%
      of the electron dose known to cause electron beam damage, show no lateral
      compositional fluctuations, but do exhibit one to four atomic plane steps in the
      active layer's upper boundary. The area imaged was measured to be 2.9 nm thick
      using position averaged convergent beam electron diffraction, ensuring the sample
      was thin enough to capture compositional variation if it was present. A focused
      ion beam prepared sample with a very large thin area provides the possibility to
      directly observe large fluctuations in the active layer thickness that constrict
      the active layer at an average lateral length scale of 430 nm.

PMID- 24667067
TI  - [Number of suicides in Spain: differences between data from the Spanish
      Statistical Office and the Institutes of Legal Medicine].
AB  - BACKGROUND AND OBJECTIVES: To be able to prevent suicides, The exact magnitude of
      suicides must be known in order to prevent them. There is evidence that data
      provided on the number of suicides by the Spanish Statistical Office (Instituto
      Nacional de Estadistica [INE]) differs from that identified by forensic
      pathologists. This paper aims to determine whether the INE data are to the same
      as those recorded by the agencies responsible for conducting autopsies in Spain
      (IML), and calculate the number of missing cases. METHOD: IML were requested to
      provide the number of suicides in a five year period (2006-2010) and this was
      compared with those offered by INE in its site. A new rate of suicides per
      100,000 was obtained and used to calculate the number of suicides in Spain.
      RESULTS: For every year of the studied period, the number of suicides reported by
      the INE was lower than that obtained directly from the IML. Using the highest
      annual suicide rate registered by province and the total, a count was obtained of
      identified suicides that for some reason had not been recorded in the INE or the
      IML data. Based on these figures, the mean rate of suicides per 100,000 was 0.97
      (SD 0.10) higher than official INE data, which indicates a mean loss of 443.86
      (SD 46.72) cases reported each year. Possible factors that may influence the
      missing recorded cases are discussed. CONCLUSIONS: According to the results,
      there is a discrepancy between INE and IML about the number of suicides in Spain.
      Neither of the two sources can be considered more reliable than the other.

PMID- 24667068
TI  - Plasma vitamin D and serum total immunoglobulin E levels in patients with
      seasonal allergic conjunctivitis.
AB  - PURPOSE: To evaluate plasma 25-hydroxyvitamin D and serum total immunoglobulin E
      (IgE) levels in patients with seasonal allergic conjunctivitis (SAC). METHODS:
      This observational case-control study involved 49 patients with SAC without any
      other ocular and systemic diseases, and 44 consecutive, age- and sex-matched
      healthy subjects. Plasma 25-hydroxyvitamin D and serum total IgE levels of all
      subjects were quantified with electrochemiluminescence technique. Results were
      compared between the groups, and p values of <0.05 were considered as
      statistically significant. RESULTS: No significant differences were found between
      the groups with respect to age (p = 0.41) and sex (p = 0.98). Plasma vitamin D
      levels of the subjects with SAC (median 8.03 ng/ml, range 3.00-17.97 ng/ml) were
      significantly lower than the control group (median 10.52 ng/ml, range 3.30-25.92
      ng/ml) (p = 0.007). Serum total IgE levels of patients with SAC (median 48.65
      IU/ml, range 1.77-812.00 IU/ml) were significantly higher when compared to the
      control group (median 32.49 IU/ml, range 0.14-104.60 IU/ml) (p = 0.003).
      CONCLUSIONS: We found lower plasma vitamin D levels and higher serum total IgE
      levels in patients with SAC.

PMID- 24667069
TI  - Thermal stability and refolding capability of shark derived single domain
      antibodies.
AB  - Single-domain antibodies (sdAb) from camelids and sharks represent the smallest
      immunoglobulin-based functional binding domains, and are known for their thermal
      stability and ability to refold after denaturation. Whereas target-binding sdAb
      have been derived from both immunized and naive sharks and camelids, the
      stability of camelid-derived sdAb have been evaluated much more extensively. To
      address this disparity we characterized 20 sdAb derived from spiny dogfish shark
      and smooth dogfish shark in terms of their protein production, melting
      temperature and ability to refold after heat denaturation. Using the same
      expression system and protocol as we follow to produce camelid sdAb, production
      of the shark sdAb was quite poor, often resulting in less than a tenth of the
      typical yield for camelid sdAb. We measured the melting temperature of each of
      the sdAb. Similar to camelid sdAb, the shark-derived sdAb, showed a range of
      melting temperature values from 42 degrees C to 77 degrees C. Also similar to
      what has been observed in camelids, the sdAb from both shark species showed a
      range of ability to refold after heat denaturation. This work demonstrated that
      although shark sdAb can possess high melting temperatures and refolding ability,
      no clear advantage over sdAb derived from camelids in terms of thermostability
      and renaturation was obtained. 

PMID- 24667070
TI  - Characterization of an anti-Bla g 1 scFv: epitope mapping and cross-reactivity.
AB  - Bla g 1 is a major allergen from Blatella germanica and one of the primary
      allergens used to assess cockroach allergen exposure. The epitope of an anti-Bla
      g 1 scFv was mapped in order to better understand cross reactivity with other
      group 1 cockroach allergens and patient IgE epitopes. X-ray crystallography was
      used to determine the structure of the scFv. The scFv epitope on Bla g 1 was
      located by alanine scanning site-directed mutagenesis and ELISA. Twenty-six rBla
      g 1-GST alanine mutants were evaluated for variations in binding to the scFv
      compared to the wild type allergen. Six mutants showed a significant difference
      in scFv binding affinity. These mutations clustered to form a discontinuous
      epitope mainly comprising two helices of Bla g 1. The allergen-scFv complex was
      modeled based on the results, and the epitope region was found to have low
      sequence similarity with Per a 1, especially among the residues identified as
      functionally important for the scFv binding to Bla g 1. Indeed, the scFv failed
      to bind Per a 1 in American cockroach extract. The scFv was unable to inhibit the
      binding of IgE antibodies from a highly cockroach allergic patient to Bla g 1.
      Based on the surface area of Bla g 1 occluded by the scFv, putative regions of
      patient IgE-Bla g 1 interactions can be inferred. This scFv could be best
      utilized as a capture antibody in an IgE detection ELISA, or to differentiate Bla
      g 1 from Per a 1 in environmental exposure assays. 

PMID- 24667071
TI  - Altered DNA methylation profile in Norwegian patients with Autoimmune Addison's
      Disease.
AB  - Autoimmune Addison's Disease (AAD) is an endocrine and immunological disease of
      uncertain pathogenesis resulting from the immune system's destruction of the
      hormone producing cells of the adrenal cortex. The underlying molecular
      mechanisms are largely unknown, but it is commonly accepted that a combination of
      genetic susceptibility and environmental impact is critical. In the present
      study, we identified multiple hypomethylated gene promoter regions in patients
      with isolated AAD using DNA isolated from CD4+ T cells. The identified
      differentially methylated regions were distributed evenly across the 10.5-kb
      promoter regions covered by the array, and a substantial number localized to
      promoters of genes involved in immune regulation and autoimmunity. This study
      reveals a hypomethylated status in CD4+ T cells from AAD patients and indicates
      differential methylation of promoters of key genes involved in immune responses. 

PMID- 24667072
TI  - Severity of cough in idiopathic pulmonary fibrosis is associated with MUC5 B
      genotype.
AB  - BACKGROUND: A polymorphism (rs35705950) in the promoter region of the mucin MUC5B
      is associated with both familial and sporadic forms of idiopathic pulmonary
      fibrosis. (IPF) We hypothesize that this common MUC5B variant will impact the
      expression of cough, a frequent disabling symptom seen in subjects with IPF.
      METHODS: We genotyped 136 subjects with IPF. All living subjects were provided
      with a Leicester Cough Questionnaire (LCQ) to measure cough severity. We assessed
      allele effects of the MUC5B polymorphism on the LCQ scores using SAS General
      Linear Models (GLM) in the patients with IPF. RESULTS: In the 68 of the total 136
      IPF patients who returned the LCQ, MUC5B minor allele frequency (T) is consistent
      with prior published studies (31%). We found a significant independent effect of
      the T allele on the LCQ score (p = 0.002 for subjects with IPF). This effect is
      independent of other common causes of cough, including gastroesophogeal reflux
      disease and upper airway cough syndrome. CONCLUSIONS: Cough severity, a common
      disabling phenotypic component of IPF, is significantly associated with the
      presence of the minor allele of a MUC5B promoter polymorphism. This study
      highlights a possible genetic mechanism for phenotypic heterogeneity in pulmonary
      fibrosis.

PMID- 24667075
TI  - Surface coverage dictates the surface bio-activity of D-amino acid oxidase.
AB  - This work presents a systematic study on the relationship between the adsorption
      mechanism and the surface bio-activity of D-amino acid oxidase (pkDAAO). This
      rational approach is based on measuring the characteristic filling and relaxation
      times under different experimental conditions. With such a goal, real-time
      adsorption-desorption experiments at different degrees of surface coverage were
      performed tuning the electrostatic and hydrophobic interactions by changing the
      pH condition for the adsorption and the substrate properties (silica or gold).
      Surface bio-activity was measured in situ by amperometry using the bio-functional
      surface as the working electrode and ex situ by spectrophotometry. On both solid
      substrates, pkDAAO adsorption is a transport-controlled process, even under
      unfavorable electrostatic interactions (charged protein and substrate with the
      same sign) due to the high percentage of basic amino acids in the enzyme. On
      silica, the relaxation step is electrostatic in nature and occurs in the same
      time-scale as filling the surface when the substrate and the enzyme are
      oppositely charged at low surface coverage. Under unfavorable electrostatic
      conditions, the relaxation (if any) occurs at long time. Accordingly, the bio
      activity of the native pkDAAO is preserved at any surface coverage. On gold, this
      step is driven by hydrophobic interactions (pH-independent) and the surface bio
      activity is highly dependent on the degree of surface coverage. Under these
      conditions, the surface bio-activity is preserved only at high surfaces coverage.
      Our results clearly indicate that pkDAAO bio-functionalized surfaces cannot be
      coupled to amperometry because the analyte interferes the electrochemical signal.
      However, this simple bio-functionalized strategy can be joined to other detection
      methods.

PMID- 24667074
TI  - Assessing the complications and effectiveness of open carpal tunnel release in a
      tertiary care centre in a developing country.
AB  - INTRODUCTION: Open surgical release for carpal tunnel syndrome is not devoid of
      complications and its quantitative assessment with the Boston questionnaire in a
      developing country had not been conducted, where, lack of facilities and surgical
      technique can influence the outcome. PRESENTATION OF CASE: This was a prospective
      study in which all cases of carpal tunnel syndrome undergoing open release
      between June 2007 and June 2012 and who returned for follow up were included.
      Each patient was requested to fill out the Boston questionnaire twice both pre
      and post op at 3 months. All complications were recorded as well as bio-data of
      patients and co morbidities. Follow up was at 2 weeks and at 3 months. Those
      reporting complications at 3 months were further followed up until 6 months. 373
      patients were included in the study. Twenty four patients developed
      complications. Of these, 12 experienced pain resulting from reflex sympathetic
      dystrophy. Three patients developed wound dehiscence, 2 cases acquired
      infections, 4 patients developed immediate post-operative haemorrhage and in 3
      patients there was late recurrence of median nerve compression. The symptom
      severity score pre-operatively was 3.30 (+/-0.60) and it improved to 1.65 (+/
      0.75) post-operatively indicating a significant change (p<0.0001). The
      preoperative functional status score was 2.58 (+/-0.75) and post-op it became
      1.60 (+/-0.80) again implying a good improvement with an effect size of 1.3.
      DISCUSSION: All of the complications produced were well managed. The complication
      incidence was low. The open release procedure produced good improvement in hand
      function and in decreasing the symptom severity. CONCLUSION: Conducting open
      release for carpal tunnel syndrome in a tertiary referral centre in a developing
      country offers a good outcome.

PMID- 24667073
TI  - A prospective comparative study of risperidone long-acting injectable for
      treatment-resistant schizophrenia with dopamine supersensitivity psychosis.
AB  - OBJECTIVE: Dopamine supersensitivity psychosis (DSP) is considered to be one
      cause of treatment-resistant schizophrenia (TRS). The authors investigated the
      efficacy of risperidone long-acting injections (RLAI) in patients with TRS and
      DSP. METHOD: This is a multicenter, prospective, 12-month follow-up,
      observational study that included unstable and severe TRS patients with and
      without DSP. 115 patients with TRS were recruited and divided into two groups
      according to the presence or absence of DSP which was judged on the basis of the
      clinical courses and neurological examinations. RLAI was administered
      adjunctively once every 2weeks along with oral antipsychotics. We observed
      changes in scores for the Brief Psychiatric Rating Scales (BPRS), Clinical Global
      Impression-Severity of Illness (CGI-S), Global Assessment of Functioning Scale
      (GAF), and Extrapyramidal Symptom Rating Scale (ESRS) during the study. Of the
      assessed 94 patients, 61 and 33 were categorized into the DSP and NonDSP groups,
      respectively. RESULTS: While baseline BPRS total scores, CGI-S scores and GAF
      scores did not differ, the ESRS score was significantly higher in the DSP group
      compared with the NonDSP group. Treatment significantly reduced BPRS total scores
      and CGI-S scores, and increased GAF scores in both groups, but the magnitudes of
      change were significantly greater in the DSP group relative to the NonDSP group.
      ESRS scores were also reduced in the DSP group. Responder rates (>=20% reduction
      in BPRS total score) were 62.3% in the DSP group and 21.2% in the NonDSP group.
      CONCLUSIONS: It is suggested that DSP contributes to the etiology of TRS.
      Atypical antipsychotic drugs in long-acting forms, such as RLAI, can provide
      beneficial effects for patients with DSP. CLINICAL TRIALS REGISTRATION: UMIN
      (UMIN000008487).

PMID- 24667076
TI  - Ion pairing with linoleic acid simultaneously enhances encapsulation efficiency
      and antibacterial activity of vancomycin in solid lipid nanoparticles.
AB  - Ion pairing of a fatty acid with an antibiotic may be an effective strategy for
      formulation optimization of a nanoantibiotic system. The aim of this study was
      therefore to explore the potential of linoleic acid (LA) as an ion pairing agent
      to simultaneously enhance encapsulation efficiency and antibacterial activity of
      triethylamine neutralized vancomycin (VCM) in solid lipid nanoparticles (SLNs).
      The prepared VCM-LA2 conjugate was characterized by Fourier transform-infrared
      (FT-IR) spectroscopy, logP and binding energy calculations. The shifts in the FT
      IR frequencies of COOH, NH2 and CO functionalities, an increase in logP value
      (1.37) and a lower interaction energy between LA and VCM (-125.54 kcal/mol)
      confirmed the formation of the conjugate. SLNs were prepared by a hot
      homogenization and ultrasonication method, and characterized for size,
      polydispersity index (PI), zeta potential (ZP), entrapment efficiency (%EE),
      surface morphology and physical stability. In vitro antibacterial activity
      studies against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA)
      were conducted. Size, PI and ZP for VCM-LA2_SLNs were 102.7+/-1.01, 0.225+/-0.02
      and -38.8+/-2.1 (mV) respectively. SLNs were also stable at 4  degrees C for 3
      months. %EE for VCM-HCl_SLNs and VCM-LA2_SLNs were 16.81+/-3.64 and 70.73+/-5.96
      respectively, indicating a significant improvement in encapsulation of the drug
      through ion pairing with LA. Transmission electron microscopy images showed
      spherical nanoparticles with sizes in the range of 95-100 nm. After 36 h, VCM-HCl
      showed no activity against MRSA. However, the minimum inhibitory concentration
      for VCM-HCl_SLNs and VCM-LA2_SLNs were 250 and 31.25 MUg/ml respectively against
      S. aureus, while against MRSA it was 500 and 15.62 MUg/ml respectively. This
      confirms the enhanced antibacterial activity of VCM-LA2_SLNs over VCM-HCl_SLNs.
      These findings therefore suggest that VCM-LA2_SLNs is a promising nanoantibiotic
      system for effective treatment against both sensitive and resistant S. aureus
      infections.

PMID- 24667077
TI  - Cellular response to rare earth mixtures (La and Gd) as components of degradable
      Mg alloys for medical applications.
AB  - Rare earth (RE) elements have been proposed to improve the corrosion resistance
      of degradable Mg alloys for medical applications. However, good biocompatibility
      of the elements released by Mg alloys during degradation is essential for their
      use in implants. Most studies are focused on material science and engineering
      aspects, but the effects of ions released at the biological interface are not
      frequently addressed. The aim of this study was to contribute to the knowledge of
      in vitro toxicological effects of two RE Mg-alloying elements, La and Gd, as
      individual ions and in mixtures with and without Mg ions. Different combinations
      (Mg+Gd, Mg+La, and Mg+Gd+La) were used to evaluate their possible synergistic
      effects on CHO-K1 cells. Two sets of experiments were designed to assess (1) the
      cyto-genotoxic effect of La and Gd ions by neutral red (NR) technique, Reduction
      of tetrazolium salt (MTT), Viability with Acridine Orange staining, Clonogenic
      test, and Comet assay; and, (2) the possible synergistic toxicological effect of
      La and Gd ions in mixtures, and the influence of osmolarity increase on cellular
      response. Cytotoxic effects of RE were found at concentrations >=200 MUM RE while
      DNA damage was detected for doses >=1500 MUM and >=1600 MUM for La and Gd,
      respectively. When mixtures of ions were evaluated, neither synergistic cytotoxic
      effects nor biological damage related to osmolarity increase were detected.

PMID- 24667078
TI  - Effect of antiplatelet/anticoagulant therapy on severe ischemic complications in
      patients with giant cell arteritis: a cumulative meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of antiplatelet/anticoagulant therapy on the
      occurrence of severe ischemic complications in GCA patients at diagnosis and
      while on treatment with corticosteroids (CS), and the risk of bleeding in these
      patients. METHODS: A comprehensive search of PubMed and the Cochrane Central
      Register of Controlled Trials databases was completed and supplemented by hand
      searching of the references of all selected articles published from 1992 through
      December 2012. The cumulative meta-analysis included 6 retrospective studies that
      provided a total of 914 GCA patients. The effect of established
      antiplatelet/anticoagulant therapy on the occurrence of severe ischemic
      complications in patients with GCA at diagnosis and on the development of new
      severe ischemic complications in patients with GCA after diagnosis and while on
      treatment with CS were evaluated; as well as the risk of bleeding in patients
      with GCA on concomitant treatment with CS and antiplatelet/anticoagulant therapy.
      RESULTS: Antiplatelet/anticoagulant therapy before the diagnosis of GCA was not
      associated with a protection to develop severe ischemic complications (OR: 0.661;
      95% CI [0.287-1.520]; p=0.33). However, such a therapy may prevent from severe
      ischemic complications after the diagnosis of GCA (OR: 0.318; [0.101-0.996];
      p=0.049) without increasing the risk of bleeding in patients with GCA on
      concomitant treatment with CS (OR: 0.658; [0.089-4.856]; p=0.682). CONCLUSIONS:
      Antiplatelet/anticoagulant therapy prior to the diagnosis of GCA was not
      associated with reduction in severe ischemic complications. However,
      antiplatelet/anticoagulant therapy demonstrated a marginal benefit when used
      together with CS therapy in patients with established GCA without associated
      bleeding risk.

PMID- 24667080
TI  - Struck-off doctor refuses to attend "farcical" regulatory hearing.

PMID- 24667079
TI  - Cell Therapy With G-CSF-Mobilized Stem Cells in a Rat Osteoarthritis Model.
AB  - G-CSF-mobilized peripheral blood stem cells (gm-PBSCs) offer a convenient cell
      source for treatment of hematopoietic and vascular disorders. Whether gm-PBSCs
      provide beneficial effects on skeleton diseases, such as osteoarthritis (OA),
      remains unknown. This study was undertaken to address the hypothesis that gm
      PBSCs promote articular regeneration in OA. Here we studied the effect of single
      dose intra-articular injection of gm-PBSCs from male donors delivered in
      hyaluronic acid (HA) on papain-induced OA in the knee joints of female Sprague
      Dawley (SD) rats. Contralateral OA knee joints received single-dose HA alone and
      served as vehicle controls. We evaluated the histologic changes in
      glycosaminoglycan, type II collagen, type X collagen, modified Mankin score, and
      cell apoptosis rate in the articular cartilage of rat knees. We demonstrated that
      gm-PBSCs were mobilized to the peripheral blood via G-CSF infusion for 5 days in
      SD rats with increasing CD34(+) percentage up to 55-fold. We showed that gm-PBSCs
      inhibit progression of papain-induced OA via reducing articular surface
      irregularity, fibrillation, and erosion, preventing cellular necrosis and loss of
      chondrogenic proteins, such as glycosaminoglycan and type II collagen, at both 3
      and 6 weeks after treatment. Moreover, gm-PBSCs reduced modified Mankin scores
      and cellular apoptosis rates compared with HA alone. Our findings demonstrate
      that HA plus gm-PBSCs, rather than HA alone, inhibits progression of OA in rats
      in vivo. Thus, intra-articular injection of gm-PBSCs is a convenient protocol for
      treating OA with consistent beneficial effects. 

PMID- 24667082
TI  - Sapropterin dihydrochloride use in pregnant women with phenylketonuria: an
      interim report of the PKU MOMS sub-registry.
AB  - For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine
      (Phe)<360MUmol/L is critical due to the toxicity of elevated Phe to the fetus.
      Sapropterin dihydrochloride (sapropterin) lowers blood Phe in tetrahydrobiopterin
      (BH4) responsive patients with PKU, in conjunction with a Phe-restricted diet,
      but clinical evidence supporting its use during pregnancy is limited. As of June
      3, 2013, the Maternal Phenylketonuria Observational Program (PKU MOMS) sub
      registry contained data from 21 pregnancies - in women with PKU who were treated
      with sapropterin either before (N=5) or during (N=16) pregnancy. Excluding data
      for spontaneous abortions (N=4), the data show that the mean of median blood Phe
      [204.7+/-126.6MUmol/L (n=14)] for women exposed to sapropterin during pregnancy
      was 23% lower, and had a 58% smaller standard deviation, compared to blood Phe
      [267.4+/-300.7MUmol/L (n=3)] for women exposed to sapropterin prior to pregnancy.
      Women on sapropterin during pregnancy experienced fewer blood Phe values above
      the recommended 360MUmol/L threshold. When median blood Phe concentration was
      <360MUmol/L throughout pregnancy, 75% (12/16) of pregnancy outcomes were normal
      compared to 40% (2/5) when median blood Phe was >360MUmol/L. Severe adverse
      events identified by the investigators as possibly related to sapropterin use
      were premature labor (N=1) and spontaneous abortion (N=1) for the women and
      hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital
      malformation (cleft palate) of unknown etiology was reported as unrelated to
      sapropterin. Although there is limited information regarding the use of
      sapropterin during pregnancy, these sub-registry data show that sapropterin was
      generally well-tolerated and its use during pregnancy was associated with lower
      mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is
      without question, sapropterin should be considered as a treatment option in
      pregnant women with PKU who cannot achieve recommended ranges of blood Phe with
      dietary therapy alone. 

PMID- 24667083
TI  - Maiden outbreaks of dengue virus 1 genotype III in rural central India.
AB  - Dengue is regarded as the most important arboviral disease. Although sporadic
      cases have been reported, serotypes responsible for outbreaks have not been
      identified from central India over the last 20 years. We investigated two
      outbreaks of febrile illness, in August and November 2012, from Korea district
      (Chhattisgarh) and Narsinghpur district (Madhya Pradesh), respectively. Fever and
      entomological surveys were conducted in the affected regions. Molecular and
      serological tests were conducted on collected serum samples. Dengue-specific
      amplicons were sequenced and phylogenetic analyses were performed. In Korea and
      Narsinghpur districts 37.3% and 59% of cases were positive, respectively, for
      dengue infection, with adults being the worst affected. RT-PCR confirmed dengue
      virus serotype 1 genotype III as the aetiology. Ninety-six percent of infections
      were primary. This is the first time that dengue virus 1 outbreaks have been
      documented from central India. Introduction of the virus into the population and
      a conducive mosquitogenic environment favouring increased vector density caused
      the outbreak. Timely diagnosis and strengthening vector control measures are
      essential to avoid future outbreaks.

PMID- 24667081
TI  - Phenylketonuria Scientific Review Conference: state of the science and future
      research needs.
AB  - New developments in the treatment and management of phenylketonuria (PKU) as well
      as advances in molecular testing have emerged since the National Institutes of
      Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science
      Conference was convened in 2012 to address new findings, particularly the use of
      the medication sapropterin to treat some individuals with PKU, and to develop a
      research agenda. Prior to the 2012 conference, five working groups of experts and
      public members met over a 1-year period. The working groups addressed the
      following: long-term outcomes and management across the lifespan; PKU and
      pregnancy; diet control and management; pharmacologic interventions; and
      molecular testing, new technologies, and epidemiologic considerations. In a
      parallel and independent activity, an Evidence-based Practice Center supported by
      the Agency for Healthcare Research and Quality conducted a systematic review of
      adjuvant treatments for PKU; its conclusions were presented at the conference.
      The conference included the findings of the working groups, panel discussions
      from industry and international perspectives, and presentations on topics such as
      emerging treatments for PKU, transitioning to adult care, and the U.S. Food and
      Drug Administration regulatory perspective. Over 85 experts participated in the
      conference through information gathering and/or as presenters during the
      conference, and they reached several important conclusions. The most serious
      neurological impairments in PKU are preventable with current dietary treatment
      approaches. However, a variety of more subtle physical, cognitive, and behavioral
      consequences of even well-controlled PKU are now recognized. The best outcomes in
      maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained
      between 120 and 360 MUmol/L before and during pregnancy. The dietary management
      treatment goal for individuals with PKU is a blood Phe concentration between 120
      and 360 MUmol/L. The use of genotype information in the newborn period may yield
      valuable insights about the severity of the condition for infants diagnosed
      before maximal Phe levels are achieved. While emerging and established genotype
      phenotype correlations may transform our understanding of PKU, establishing
      correlations with intellectual outcomes is more challenging. Regarding the use of
      sapropterin in PKU, there are significant gaps in predicting response to
      treatment; at least half of those with PKU will have either minimal or no
      response. A coordinated approach to PKU treatment improves long-term outcomes for
      those with PKU and facilitates the conduct of research to improve diagnosis and
      treatment. New drugs that are safe, efficacious, and impact a larger proportion
      of individuals with PKU are needed. However, it is imperative that treatment
      guidelines and the decision processes for determining access to treatments be
      tied to a solid evidence base with rigorous standards for robust and consistent
      data collection. The process that preceded the PKU State-of-the-Science
      Conference, the conference itself, and the identification of a research agenda
      have facilitated the development of clinical practice guidelines by professional
      organizations and serve as a model for other inborn errors of metabolism.

PMID- 24667085
TI  - Community responses of intertidal soft-bottom macrozoobenthos to oil pollution in
      a tropical mangrove ecosystem, Niger Delta, Nigeria.
AB  - Preliminary impact assessment of two large oil spill incidents at Bodo Creek, in
      the Niger Delta, was undertaken, focusing on intertidal macrozoobenthos. Post
      spill number of species and abundance were measured against recent pre-spill
      baseline data from the same study area. Results show that surface and infauna
      communities suffered severe reduction in abundance and number of species reduced
      by 81% after the spills, with two of the resampled sites having no taxa at all.
      Capitella capitata populations increased several-fold over pre-spill numbers. The
      impact of the oil spills is discussed in relation to local livelihoods and
      ecosystem integrity. The Niger Delta endemic lucinid, Keletistes rhizoecus, is
      proposed as a potential bioindicator for monitoring hydrocarbon contamination in
      Niger Delta estuaries. 

PMID- 24667086
TI  - Macrobenthic succession and characteristics of a man-made intertidal sandflat
      constructed in the diversion channel of the Ohta River Estuary.
AB  - We compared succession and characteristics of the macrobenthic community in a
      small-scale experimental intertidal sandflat constructed in the artificial
      diversion channel of the Ohta River Estuary with those of three natural
      intertidal sandflats at lower elevation in the same channel. The macrobenthic
      population density in the man-made intertidal sandflat increased significantly
      between 3 and 9 months after construction. Simplisetia erythraeensis was dominant
      (98% of individuals) after 9 months, but its proportion gradually declined with
      the increase in biodiversity until 26 months, indicating that succession of the
      macrobenthic community was nearly complete by 26 months. The macrobenthic
      community in the man-made intertidal sandflat differed from those of the three
      natural intertidal sandflats, and its population density was about double that at
      the natural sites, with smaller temporal fluctuation. The different structures of
      the macrobenthic communities in the man-made and natural intertidal sandflats
      were likely caused by differences in elevation.

PMID- 24667084
TI  - Prospective study of high-risk, BRCA1/2-mutation negative women: the 'negative
      study'.
AB  - BACKGROUND: We previously reported that women from high-risk families who tested
      negative for a BRCA1 or BRCA2 (BRCA1/2) mutation were four times more likely to
      develop breast cancer compared to women in the general population. Preventive
      measures and risk factors for breast cancer development in these high-risk women
      have not been evaluated to the same extent as BRCA1/2 positive women. Further,
      there is virtually no scientific evidence about best practices in their
      management and care. The proposed study will examine a role of genetic and non
      genetic factors and develop the systems and parameters for the monitoring and
      surveillance necessary to help establish guidelines for the care of this high
      risk population. METHODS/DESIGN: To achieve our goals, we will assemble and
      follow a Canadian cohort of 1,000 cancer-free women with a strong family history
      breast cancer (defined as two or more relatives affected by breast cancer under
      the age of 50, or three or more relatives diagnosed with breast cancer at any age
      from one side of the family and with no BRCA1/2 mutation in the family). All
      eligible participants will be mailed a study package including invitation to
      participate, consent form, a research questionnaire to collect data regarding
      family history, reproductive and lifestyle factors, as well as screening and
      surgery. Usual dietary intake will be assessed by a diet history questionnaire.
      Biological samples including toenail clippings, urine and blood samples will be
      collected. These women will be followed every two years by questionnaire to
      update exposure information, screening practices, surgical and chemoprevention,
      and disease development. DISCUSSION: Findings from this study will serve to help
      establish clinical guidelines for the implementation of prevention, counseling,
      and treatment practices for women who face an elevated risk of breast cancer due
      to family history, but who do not carry a BRCA1/2 mutation.

PMID- 24667087
TI  - Reproductive long-term effects, endocrine response and fatty acid profile of
      rabbit does fed diets supplemented with n-3 fatty acids.
AB  - The effect of a diet enriched with polyunsaturated n-3 fatty acids (PUFA) on
      endocrine, reproductive, and productive responses of rabbit females and the
      litters has been studied. Nulliparous does (n=125) were fed ad libitum from
      rearing to second weaning two diets supplemented with different fat sources:
      7.5g/kg lard for the control diet (group C; n=63) or 15g/kg of a commercial
      supplement containing a 50% ether extract and 35% of total fatty acids (FAs) as
      PUFA n-3 (Group P; n=62). Dietary treatments did not affect apparent
      digestibility coefficients of nutrients, or reproductive variables of does
      including milk production, mortality and average daily gain of kits over two
      lactations. However, on Day 5 and 7 post-induction of ovulation, progesterone of
      Group P tended to increase to a greater extent than in does of Group C. Total
      PUFAs, n-6 and n-3 and eicosapentanoic (EPA) contents were greater in adipose
      tissues of does in Group P than in Group C. Docosapentaenoic acid (DPA), EPA, and
      docosahexaenoic acid (DHA) concentrations were greater in peri-ovarian than in
      scapular fat with abdominal fat being intermediate in concentration. In PUFA
      supplemented does, kit mortality at the second parturition tended to be less than
      in control does. Also, kits born to does of the PUFA-supplemented group weighed
      more and were of greater length than from does of control group. In conclusion,
      effectiveness of dietary intervention on reproductive and performance response is
      greater in the second parity, which suggests an accumulative long-term beneficial
      effect of n-3 FA supplementation in reproductive rabbit does. 

PMID- 24667088
TI  - Role of MMP-9 in the breakdown of barrier integrity of the corneal endothelium in
      response to TNF-alpha.
AB  - TNF-alpha induces loss of barrier integrity of the corneal endothelium through
      mechanisms involving the activation of p38 MAP kinase. This study has
      investigated the role of matrix metalloproteinase-9 (MMP-9), known to be
      activated by mechanisms downstream of p38 MAP kinase, on the breakdown of the
      barrier integrity. Experiments were performed with primary cultures of bovine
      corneal endothelium. Changes in the trans-endothelial electrical resistance
      (TER), a measure of barrier integrity, were measured by electric cell-substrate
      impedance sensing. The integrity of the apical junctional assembly was imaged by
      immunolocalization of ZO-1. MMP-9 activity in the conditioned medium of cells
      treated with TNF-alpha was visualized by gelatin zymography. Transcriptional
      activation of MMP-9 was assessed by real-time RT-PCR. Exposure to TNF-alpha led
      to significant disruption of ZO-1 and also caused a continuous decline in TER for
      more than 20 h. These effects were opposed by cycloheximide (protein synthesis
      inhibitor), GM-6001 (broad spectrum inhibitor of MMPs), minocycline (MMP-2 and
      MMP-9 inhibitor), and MMP-9 inhibitor I (selective MMP-9 inhibitor).
      Cycloheximide, GM-6001, and MMP-9 inhibitor I also attenuated the increase in
      permeability to FITC-dextran (10 kDa). In addition, TNF-alpha led to an increased
      MMP-9 activity in the conditioned medium as well as a nearly 20-fold increase in
      mRNA for MMP-9 but not for MMP-2. The functional activity and increase in mRNA
      levels of MMP-9 were blocked by SB-203580 (selective p38 MAP kinase inhibitor)
      and cycloheximide. In conclusion, transcriptional and translational activation of
      MMP-9, downstream of p38 MAP kinase signaling, is involved in the (TNF-alpha)
      induced loss of corneal endothelial barrier integrity. 

PMID- 24667089
TI  - The PEG13-DMR and brain-specific enhancers dictate imprinted expression within
      the 8q24 intellectual disability risk locus.
AB  - BACKGROUND: Genomic imprinting is the epigenetic marking of genes that results in
      parent-of-origin monoallelic expression. Most imprinted domains are associated
      with differentially DNA methylated regions (DMRs) that originate in the gametes,
      and are maintained in somatic tissues after fertilization. This allelic
      methylation profile is associated with a plethora of histone tail modifications
      that orchestrates higher order chromatin interactions. The mouse chromosome 15
      imprinted cluster contains multiple brain-specific maternally expressed
      transcripts including Ago2, Chrac1, Trappc9 and Kcnk9 and a paternally expressed
      gene, Peg13. The promoter of Peg13 is methylated on the maternal allele and is
      the sole DMR within the locus. To determine the extent of imprinting within the
      human orthologous region on chromosome 8q24, a region associated with autosomal
      recessive intellectual disability, Birk-Barel mental retardation and dysmorphism
      syndrome, we have undertaken a systematic analysis of allelic expression and DNA
      methylation of genes mapping within an approximately 2 Mb region around TRAPPC9.
      RESULTS: Utilizing allele-specific RT-PCR, bisulphite sequencing, chromatin
      immunoprecipitation and chromosome conformation capture (3C) we show the
      reciprocal expression of the novel, paternally expressed, PEG13 non-coding RNA
      and maternally expressed KCNK9 genes in brain, and the biallelic expression of
      flanking transcripts in a range of tissues. We identify a tandem-repeat region
      overlapping the PEG13 transcript that is methylated on the maternal allele, which
      binds CTCF-cohesin in chromatin immunoprecipitation experiments and possesses
      enhancer-blocker activity. Using 3C, we identify mutually exclusive approximately
      58 and 500 kb chromatin loops in adult frontal cortex between a novel brain
      specific enhancer, marked by H3K4me1 and H3K27ac, with the KCNK9 and PEG13
      promoters which we propose regulates brain-specific expression. CONCLUSIONS: We
      have characterised the molecular mechanism responsible for reciprocal allelic
      expression of the PEG13 and KCNK9 transcripts. Therefore, our observations may
      have important implications for identifying the cause of intellectual
      disabilities associated with the 8q24 locus.

PMID- 24667090
TI  - Nutrition-education program improves preschoolers' at-home diet: a group
      randomized trial.
AB  - OBJECTIVE: This study evaluated whether a nutrition-education program in child
      care centers improved children's at-home daily consumption of fruits and
      vegetables, at-home use of low-fat/fat-free milk, and other at-home dietary
      behaviors. MATERIALS AND METHODS: Twenty-four child-care centers serving low
      income families were matched by region, type, and size, and then randomly
      assigned to either an intervention or control condition. In the 12 intervention
      centers, registered dietitian nutritionists provided nutrition education to
      children and parents separately during a 6- to 10-week period. They also held two
      training sessions for center staff, to educate them on healthy eating and
      physical activity policies at the centers, and distributed weekly parent
      newsletters that included activities and recipes. Parents (n=1,143) completed a
      mail or telephone survey at baseline and follow-up to report information on their
      child's fruit, vegetable, and milk consumption and other dietary behaviors at
      home. This study used general and generalized linear mixed models to evaluate
      program impacts, while accounting for the clustering of children within centers.
      This study included child age, child sex, household size, respondent
      race/ethnicity, respondent age, and respondent sex as covariates. RESULTS: The
      program had a substantial impact on children's at-home daily consumption of
      vegetables and use of low-fat/fat-free milk. This study also found a significant
      increase in the frequency of child-initiated vegetable snacking, which might have
      contributed to the significant increase in vegetable consumption. The program did
      not have a significant impact on fruit consumption or parental offerings of
      fruits and vegetables, child-initiated fruit snacking, or child fruit
      consumption. CONCLUSIONS: This intervention in child-care settings that
      emphasized children, parents, and teachers significantly increased at-home
      vegetable and low-fat/fat-free milk consumption among low-income preschoolers.

PMID- 24667091
TI  - Clinicopathological and EBV analysis of respiratory epithelial adenomatoid
      hamartoma.
AB  - BACKGROUND: To investigate the clinicopathological characteristics of respiratory
      epithelial adenomatoid hamartoma (REAH) in residents of Southern China and to
      study the correlation between REAH and Epstein-Barr virus (EBV). METHODS:
      Clinicopathological data of 53 cases of REAH were retrospectively analyzed. The
      immunoreactivity for CK 7, CK20, CEA, p53, and Ki-67, Alcian blue-periodic acid
      Schiff (AB-PAS) staining and in situ hybridization for EBV-encoded RNA (EBER)
      were carried out. RESULTS: REAH lesions were covered with ciliated columnar
      epithelium and proliferation of subepithelial glands, which were positive for
      CK7, and negative for CK20, CEA, and p53. Goblet cell metaplasia was stained blue
      by AB-PAS. The frequency of EBER positive cases in REAH located in nasopharynx
      was 27.78%, compared with that in the nasal cavity (15.79%) and paranasal sinuses
      (12.50%), there were no statistical differences. CONCLUSIONS: REAH is an uncommon
      entity with distinctive morphologic features and EBV may have nothing to do with
      REAH. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here:http://www.diagnosticpathology.diagnomx.eu/vs/5875687401178748.

PMID- 24667092
TI  - Nucleation dynamics of water nanodroplets.
AB  - The origin of the condensation of water begins at the nanoscale, a length-scale
      that is challenging to probe for liquids. In this work we directly image
      heterogeneous nucleation of water nanodroplets by in situ transmission electron
      microscopy. Using gold nanoparticles bound to a flat surface as heterogeneous
      nucleation sites, we observe nucleation and growth of water nanodroplets. The
      growth of nanodroplet radii follows the power law: R(t)~(t-t 0) beta , where
      beta~0.2-0.3. 

PMID- 24667093
TI  - [Non-celiac gluten sensitivity: a critical review of current evidence].
AB  - Non-celiac gluten sensitivity (NCGS) is an emerging disorder characterized by
      intestinal and extra-intestinal symptoms related to the ingestion of gluten
      containing food in non-celiac patients. Its prevalence has been estimated to be
      six to ten-times higher than that of celiac disease (CD). A gluten-free diet is
      the most widely recommended therapy, but the causative agent remains unknown and
      there are no consensus diagnostic criteria. Recent studies on NCGS have included
      patients with possibly overlooked minor CD and diarrhea-predominant irritable
      bowel syndrome without self-reported gluten intolerance, but showing a response
      to a gluten-free diet. Furthermore, FODMAPs (Fermentable Oligosaccharides,
      Disaccharides, Monosaccharides And Polyols) have recently been postulated as the
      culprit component for NCGS in wheat, instead of gluten. This review updates
      evidence on the pathophysiology of NCGS and the efficacy of different dietary
      interventions in its treatment, stressing the need for proper screening for CD
      before a diagnosis of NCGS is made. 

PMID- 24667094
TI  - [Surgical options for familial adenomatous polyposis depending on genetic
      factors].

PMID- 24667095
TI  - The effect of variants in the promoter of BMPER on the intramuscular fat
      deposition in longissimus dorsi muscle of pigs.
AB  - The aim of the study was to evaluate the contribution of BMPER promoter SNPs to
      the gene expression and intramuscular fat content in longissimus dorsi muscle.
      Firstly the promoter region of BMPER was comparatively scanned by direct
      sequencing with pool DNA of two groups (n=15 for each group) with high (H) or low
      (L) IMF content. Two SNPs, c.-1423A>G and c.-1344A>C, were found to have reverse
      allele distribution in the two groups. Genotyping by PCR-SSCP in a larger
      population revealed that the two SNPs interlock completely to form only A-A or G
      C haplotype. The IMF content and BMPER expression level of A-A/A-A genotype were
      higher than G-C/G-C genotype, and luciferase assay revealed that A-A haplotype
      promoter activity was also higher than G-C haplotype. Putative transcription
      factor prediction suggested that c.-1344 A>C mutation might shift the promoter
      binding affinity with GATAs. We concluded that BMPER promoter polymorphisms have
      an effect on IMF content, and A-A haplotype could be used as a candidate genetic
      marker for preferable IMF deposition.

PMID- 24667096
TI  - Olopatadine hydrochloride restores histamine-induced impaired sweating.

PMID- 24667097
TI  - Distribution of IL-31 and its receptor expressing cells in skin of atopic
      dermatitis.
AB  - BACKGROUND: To understand the clinical segments of IL-31 signaling blockade
      therapy in pruritus of atopic dermatitis (AD), direct detection of the target
      proteins in the diseased tissues will provide crucial information. There is a
      lack of direct evidence concerning the cellular origin of IL-31 in AD skins, and
      data on the expression of IL-31RA in AD are inconsistent. Also, there is no
      available information regarding IL-31RA protein expression in human dorsal root
      ganglia (DRG), which mediates the sensation of itch and is the long-suspected
      source of the protein. OBJECTIVE: We sought to obtain direct evidence concerning
      the distribution of IL-31- and IL-31RA-protein expressing cells and their
      characteristics in AD skin samples and in human DRG. METHODS: IL-31 was detected
      immunohistochemically in AD skins, and representative sections were double
      stained with IL-31 and several immune-markers. IL-31RA was stained
      immunohistochemically in AD skins and normal human DRG, and representative AD
      skins were double stained with IL-31RA and PGP9.5 (a nerve marker). RESULTS: IL
      31-positive cells were observed as mononuclear infiltrating cells and as CD11b co
      expressing cells in severe AD samples. As for IL-31RA, positive reactions were
      detected in keratinocytes and nerve fibers in the dermis of AD and in the neurons
      of normal DRG. CONCLUSION: The detection of IL-31 in infiltrating cells of severe
      AD skin and of IL-31RA in nerve fibers of AD dermis and normal DRG indicates IL
      31 signaling may be a contributing factor in the persistence and exacerbation of
      AD skin lesions.

PMID- 24667099
TI  - Kikuchi-Fujimoto disease.

PMID- 24667098
TI  - Microbial biosynthesis of designer outer membrane vesicles.
AB  - Outer membrane vesicles (OMVs) are nanoscale proteoliposomes that are
      ubiquitously secreted by Gram-negative bacteria. Interest in these bioparticles
      has escalated over the years, leading to discoveries regarding their composition,
      production, and vaccine potential. Given that many steps in vesicle biogenesis
      are 'engineerable,' it is now possible to tailor OMVs for specific applications.
      Such tailoring involves modifying the OMV-producing bacterium through protein,
      pathway, or genome engineering in a manner that specifically alters the final OMV
      product. For example, targeted deletion or upregulation of genes associated with
      the cell envelope can modulate vesicle production or remodel the composition of
      vesicle components such as lipopolysaccharide. Likewise, bacteria can be
      reprogrammed to incorporate heterologously expressed proteins into either the
      membrane or lumenal compartment of OMVs. We anticipate that further research in
      the field of OMV engineering will enable continued design and biosynthesis of
      specialized vesicles for numerous biotechnological purposes ranging from the
      delivery of vaccines to the deconstruction of cellulosic substrates. 

PMID- 24667100
TI  - Embodied accounts of HIV and hope: using audio diaries with interviews.
AB  - Capturing the complexity of the experience of chronic illness over time presents
      significant methodological and ethical challenges. In this article, we present
      methodological and substantive insights from a longitudinal qualitative study
      with 20 people living with HIV in Serbia. We used both repeated in-depth
      interviews and audio diaries to explore the role of hope in coping with and
      managing HIV. Using thematic longitudinal analysis, we found that the audio
      diaries produced distinctive, embodied accounts that straddled the public/private
      divide and engaged with alternative social scripts of illness experience. We
      suggest that this enabled less socially anticipated accounts of coping, hoping,
      and distress to be spoken and shared. We argue that examining the influence of
      different methods on accounting not only illustrates the value of qualitative
      mixed-method study designs but also provides crucial insights to better
      understand the lived experience of chronic illness. 

PMID- 24667101
TI  - Characterization of Insulin-Secreting Porcine Bone Marrow Stromal Cells Ex Vivo
      and Autologous Cell Therapy In Vivo.
AB  - Cell therapy could potentially meet the need for pancreas and islet
      transplantations in diabetes mellitus that far exceeds the number of available
      donors. Bone marrow stromal cells are widely used in clinical trials mainly for
      their immunomodulatory effects with a record of safety. However, less focus has
      been paid to developing these cells for insulin secretion by transfection.
      Although murine models of diabetes have been extensively used in gene and cell
      therapy research, few studies have shown efficacy in large preclinical animal
      models. Here we report optimized conditions for ex vivo expansion and
      characterization of porcine bone marrow stromal cells and their permissive
      expression of a transfected insulin gene. Our data show that these cells resemble
      human bone marrow stromal cells in surface antigen expression, are homogeneous,
      and can be reproducibly isolated from outbred Yorkshire-Landrace pigs. Porcine
      bone marrow stromal cells were efficiently expanded in vitro to >10(10) cells
      from 20 ml of bone marrow and remained karyotypically normal during expansion.
      These cells were electroporated with an insulin expression plasmid vector with
      high efficiency and viability, and secreted human insulin and C-peptide
      indicating appropriate processing of proinsulin. We showed that autologous
      insulin-secreting bone marrow stromal cells implanted and engrafted in the liver
      of a streptozotocin-diabetic pig that modeled type 1 diabetes resulted in
      partial, but significant, improvement in hyperglycemia that could not be ascribed
      to regeneration of endogenous beta-cells. Glucose-stimulated insulin secretion in
      vivo from implanted cells in the treated pig was documented by a rise in serum
      human C-peptide levels during intravenous glucose tolerance tests. Compared to a
      sham-treated control pig, this resulted in significantly reduced fasting
      hyperglycemia, a slower rise in serum fructosamine, and prevented weight loss.
      Taken together, this study suggests that bone marrow stromal cells merit further
      development as autologous cell therapy for diabetes. 

PMID- 24667102
TI  - The prevalence and risk of human papillomavirus infection in pregnant women.
AB  - A series of observational studies were evaluated concerning the risk of human
      papillomavirus (HPV) infection in pregnancy; however, the results were
      controversial. We systematically reviewed and collected data on studies regarding
      HPV prevalence published up to 30 April 2013, in which HPV was detected in
      pregnant women or both in pregnant and non-pregnant women. In total, 28 eligible
      studies were included that provided data on HPV infection concerning 13 640
      pregnant women. The overall HPV prevalence in pregnant and age-matched non
      pregnant women was 16.82% [95% confidence interval (CI) 16.21-17.47] and 12.25%
      (95% CI 11.50-13.01), respectively. The prevalence in the in three trimesters was
      18.20%, 14.38%, and 19.32%, respectively. HPV-16 was the most frequently observed
      type, with a prevalence of 3.86% (95% CI 3.40-4.32). The overall HPV prevalence
      varied by study region, age, and HPV type. The meta-analysis showed a
      significantly increased risk of HPV infection in pregnant women, with a summary
      odds ratio (OR) of 1.42 (95% CI 1.25-1.61), especially for those aged <25 years
      (OR 1.79, 95% CI 1.22-2.63). The results suggest that pregnant women, especially
      those aged <25 years, are more susceptible to HPV infection.

PMID- 24667103
TI  - Dietary supplements for aquatic sports.
AB  - Many athletes use dietary supplements, with use more prevalent among those
      competing at the highest level. Supplements are often self-prescribed, and their
      use is likely to be based on an inadequate understanding of the issues at stake.
      Supplementation with essential micronutrients may be useful when a diagnosed
      deficiency cannot be promptly and effectively corrected with food-based dietary
      solutions. When used in high doses, some supplements may do more harm than good:
      Iron supplementation, for example, is potentially harmful. There is good evidence
      from laboratory studies and some evidence from field studies to support health or
      performance benefits from appropriate use of a few supplements. The available
      evidence from studies of aquatic sports is small and is often contradictory.
      Evidence from elite performers is almost entirely absent, but some athletes may
      benefit from informed use of creatine, caffeine, and buffering agents. Poor
      quality assurance in some parts of the dietary supplements industry raises
      concerns about the safety of some products. Some do not contain the active
      ingredients listed on the label, and some contain toxic substances, including
      prescription drugs, that can cause health problems. Some supplements contain
      compounds that will cause an athlete to fail a doping test. Supplement quality
      assurance programs can reduce, but not entirely eliminate, this risk. 

PMID- 24667104
TI  - Clinical spectrum of epileptic spasms in children.
AB  - PURPOSE: To compare etiologic, semiologic, and electrographic features of
      epileptic spasms (ES) in children with West syndrome (WS) vs. in children with
      other epilepsy syndromes and nonsyndromic epilepsies. METHODS: The 24h-video/EEG
      recordings of consecutive children with ES were reviewed for etiology, ictal
      semiology, and interictal and ictal EEG features. We created three objectively
      defined groups for interictal EEG: (A) background voltage > 300 MUV with multiple
      independent spike foci (MISF) and disorganization consistent with hypsarhythmia;
      (B) voltage between 200 and 300 MUV with MISF and moderate disorganization,
      similar but not identical to hypsarhythmia; (C) voltage <200MUV+/-MISF , not
      consistent with hypsarhythmia. RESULTS: We identified 161 children (group A, 70;
      group B, 32; group C, 59). The greatest difference between the groups A, B, and
      C, respectively was in age (in months) both at onset (6.4 +/- 4.4, 15.3 +/- 22.1
      and 31.6 +/- 38.1, p<0.0001) and at EEG (10.8 +/- 6.9, 22.9 +/- 26.2 and 45.6 +/-
      42.1, p<0.0001). The groups also showed some differences in the frequency of
      preceding or admixed seizures, and in seizure semiology. By contrast, there were
      no significant differences in the underlying causes or in patterns of ictal
      discharges between the groups. CONCLUSION: ES clearly exist outside of the
      confines of WS with some phenomenological variations. The causes and ictal
      patterns, however, are remarkably similar among all patients with ES. The subtle
      difference in seizure semiology may reflect maturational changes. These findings
      support the concept of a spectrum of ES with a degree of age-dependency in its
      manifestations rather than entirely different clinical entities.

PMID- 24667106
TI  - Change in Balance Confidence and Its Associations With Increasing Disability in
      Older Community-Dwelling Women at Risk for Falling.
AB  - OBJECTIVES: To describe change in balance confidence, and to identify associated
      factors and disabling consequences. METHOD: Secondary analysis of 2 years of data
      collected from 272 older women enrolled in a randomized clinical trial of fall
      prevention. Balance confidence and disability measures were assessed at baseline,
      after the 12 week intervention, and at 1 and 2 years follow-up. Associated
      factors were measured at baseline. RESULTS: Balance confidence varied at baseline
      and decreased 5% over 2 years, but no variables predicted this decline. Baseline
      balance confidence was associated with poor physical function and mental health.
      Decreasing balance confidence was associated with increasing impairments in
      balance and hip flexion strength, increasing functional limitations in mobility
      and chair rises, reduced physical activity levels, increased activity
      restrictions, and decreasing social networks. DISCUSSION: Decreasing balance
      confidence plays an important role in disablement. More research is needed to
      identify predictors of decreasing balance confidence.

PMID- 24667107
TI  - Study design and implementation of the PINE study.
AB  - OBJECTIVE: Multiple barriers in research participation have excluded the Chinese
      older adults from benefitting the recent advancement of aging sciences. The
      paucity of systematic understanding of Chinese aging population necessitated the
      Population-Based Study of Chinese Elderly in Chicago (PINE). METHOD: Guided by
      community-based participatory research approach, the PINE study is a population
      based epidemiological study of Chinese older adults aged 60 and above in the
      Greater Chicago area. RESULTS: We described study design and implantation of the
      PINE study, highlighting strategies in adapting a population-based study design
      to the Chinese community. These measures included community-engaged recruitment,
      innovative data collection methods, and culturally and linguistically sensitive
      study infrastructure. DISCUSSION: The intricate cultural and linguistic diversity
      among U.S. Chinese older adults, coupled with their demographic characteristics
      and residential pattern, present challenges and opportunities in implementing a
      population-based study of older adults. Implications for the research and
      practice in relation to future minority aging and social sciences studies are
      discussed.

PMID- 24667108
TI  - Amplification of Mdmx and overexpression of MDM2 contribute to mammary
      carcinogenesis by substituting for p53 mutations.
AB  - BACKGROUND: The p53 tumor suppressor gene is mutated or deleted in nearly half of
      human cancers. The murine double minute 2 (Mdm2) and Mdmx represent two important
      cellular regulators of p53. The aim of this study was to evaluate the
      abnormalities of p53, Mdmx and Mdm2 genes in archived breast cancers. METHODS: We
      assessed the genetic instability at p53, Mdmx and Mdm2 using high resolution
      multi-color fluorescent in situ hybridization (FISH) protocol and detected the
      expression status of the tumor protein p53 (TP53), MDMx and MDM2 by
      immunohistochemistry in 115 archived samples of infiltrating ductal breast
      carcinomas with foci of ductal carcinoma in situ (DCIS) components. RESULTS: The
      presence of p53 allelic loss and/or TP53 overexpression was observed in 38% out
      of all patients, and was significantly more often in larger, high grade, ER
      negative and high ki67 tumors. Mdmx amplification with low-level increase of gene
      copy number is at high frequency while Mdm2 amplification is rare in primary
      breast cancer. Mdmx amplification was seen in more invasive carcinomas than
      preinvasive lesions. MDMx and MDM2 overexpression were detected in 65% and 38% of
      all cases respectively. Moreover it was showed that most tumors contained either
      p53 dysfunction or Mdm2 alteration, but not both. This distribution was
      significant (P < 0.05). Inverse correlation between Mdmx
      amplification/overexpression and p53 disfunction was also observed (P < 0.05).
      CONCLUSIONS: Our results suggest the involvement of Mdm2 and Mdmx in p53
      independent breast carcinogenesis and Mdmx may contribute to the regulation of
      p53 independently of Mdm2. VIRTUAL SLIDES: The virtual slides for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1450529994118798.

PMID- 24667109
TI  - Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage:
      new therapeutic challenging opportunities.
AB  - Because maternal alloreactive lymphocytes are not depleted during pregnancy,
      local and/or systemic mechanisms have to play a key role in altering the maternal
      immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal
      interface are necessary in situ to prevent early abortion, but only those pTregs
      that have been previously exposed to paternal alloantigens. It has been showed
      that pregnancy selectively stimulates the accumulation of maternal
      Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly,
      after delivery, foetal-specific pTregs persist at elevated levels, maintain
      tolerance to pre-existing foetal antigen, and rapidly re-accumulate during
      subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible
      future therapeutic strategy in humans. 

PMID- 24667110
TI  - [Childhood obesity: have we bottomed out? Can we bring out the bubbly?].

PMID- 24667111
TI  - [Acute lymphoblastic leukemia of T progenitors: from biology to clinics].
AB  - Acute lymphoblastic leukemia (ALL) is the most common cancer in children and the
      main cause of morbidity among childhood blood disorders. There are 2 subtypes
      according to the affected lymphoid progenitor: B-ALL and T-ALL. The T-ALL is the
      less common and, although historically was associated with poor prognosis in both
      adults and children, at present, treatment outcomes do not differ significantly
      between the 2 types of ALL. The T-ALL subtype is the most complex and
      heterogeneous at the genetic level and currently the one with less new
      therapeutic alternatives available. This trend is changing thanks to the
      remarkable progress upon understanding its biology. This review summarizes the
      most recent and important biological findings in T-ALL and their possible
      therapeutic implications. 

PMID- 24667112
TI  - [Public access to the results of clinical trials with drugs: is this enough for
      practicing physicians and patients?].

PMID- 24667113
TI  - [Prediction of bacteremia: the first step of an early intervention program for
      patients discharged from the Emergency Department].

PMID- 24667114
TI  - [Vitamin D levels in elderly patients hospitalized with hip fracture].

PMID- 24667115
TI  - Enhanced catalytic site thermal stability of cold-adapted esterase EstK by a
      W208Y mutation.
AB  - Hydrophobic interactions are known to play an important role for cold-adaptation
      of proteins; however, the role of amino acid residue, Trp, has not been
      systematically investigated. The extracellular esterase, EstK, which was isolated
      from the cold-adapted bacterium Pseudomonas mandelii, has 5 Trp residues. In this
      study, the effects of Trp mutation on thermal stability, catalytic activity, and
      conformational change of EstK were investigated. Among the 5 Trp residues, W(208)
      was the most crucial in maintaining structural conformation and thermal stability
      of the enzyme. Surprisingly, mutation of W(208) to Tyr (W(208)Y) showed an
      increased catalytic site thermal stability at ambient temperatures with a 13-fold
      increase in the activity at 40 degrees C compared to wild-type EstK. The
      structure model of W(208)Y suggested that Y(208) could form a hydrogen bond with
      D(308), which is located next to catalytic residue H(307), stabilizing the
      catalytic domain. Interestingly, Tyr was conserved in the corresponding position
      of hyper-thermophilic esterases EstE1 and AFEST, which are active at high
      temperatures. Our study provides a novel insight into the engineering of the
      catalytic site of cold-adapted enzymes with increased thermal stability and
      catalytic activity at ambient temperatures.

PMID- 24667116
TI  - [Clinical relevance of drug interactions between nonsteroidal antiinflammatory
      drugs (NSAIDs) and antihypertensives].
AB  - OBJECTIVE: To establish the clinical relevance of drug interactions between
      nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensives, based on the
      interaction severity and probability of occurrence. DESIGN: Systematic review.
      DATA SOURCES: A PubMed/Medline search was made using the MeSH terms: NSAIDs,
      Antihypertensive drugs, and Drug interactions. DATA EXTRACTION: Articles between
      2002 and 2012, human studies, in Spanish and English and full text access were
      included. Found articles were included and some of the references used in this
      works. Studies with in vitro methods, effects on ocular hypertension and those
      who do not consider the interaction NSAIDs, antihypertensives were excluded. For
      the selection of the papers included three independent reviewers were involved.
      We used a tool for data extraction and for assess of the interaction clinical
      relevance. RESULTS: Nineteen of 50 papers found were included. There were
      identified 21 interactions with pharmacodynamic mechanism, classified by their
      clinical relevance in level-2 high risk (76.2%) and level-3 medium risk (23.8%).
      In addition, evidence of 16 combinations of no interaction were found.
      CONCLUSIONS: Some NSAIDs may attenuate the effectiveness of antihypertensive
      drugs when used concurrently, especially with angiotensin converting enzyme
      inhibitors, diuretics, beta blockers and angiotensin receptorsii blockers. There
      was no evidence of effect modification of calcium channel antagonists, especially
      dihydropyridine, by concurrent use of NSAIDs.

PMID- 24667117
TI  - A comprehensive association analysis confirms ZMIZ1 to be a susceptibility gene
      for vitiligo in Chinese population.
AB  - BACKGROUND: ZMIZ1 has been shown to be associated with multiple autoimmune
      diseases and play a role in the development of melanocyte. The association of
      ZMIZ1 with vitiligo was also suggested, but the evidence did not reach genome
      wide significance and has not been confirmed by independent studies. METHODS: A
      fine mapping analysis of the ZMIZ1 locus was carried out in the dataset of 1117
      vitiligo patients and 3437 controls through deep imputation. Ten suggestive SNPs
      were then analysed in an independent validation cohort of 7458 cases and 7542
      controls. SNPs within ZMIZ1 locus were functionally annotated using the ENCODE
      and RegulomeDB databases and published eQTL dataset of primary immune cells.
      RESULTS: A genome-wide significant association was discovered at rs1408944
      (OR(combined)=1.18, p(combined)=1.38E-09) that locates at a DNAse
      hypersensitivity site and within a Myb_1 motif carried by the binding sites of
      six overlapping transcription factors (TFs) within the region. Gene Relationships
      Across Implicated Loci (GRAIL) analysis revealed biological connectivity between
      ZMIZ1 and previously discovered susceptibility loci for vitiligo as well as the
      six TFs. CONCLUSIONS: Our study has confirmed ZMIZ1 as a novel susceptibility
      locus for vitiligo and further suggested rs1408944 to be the putative causal
      variant that potentially interrupts TF binding and thus the transcriptional
      regulation of ZMIZ1.

PMID- 24667118
TI  - Variable phenotypic expression of COG6 mutations.

PMID- 24667119
TI  - Expanding the clinical phenotype of COG6 deficiency.

PMID- 24667122
TI  - DDAH activity is not associated with oxidative stress in elderly patients with
      peripheral arterial occlusive disease.

PMID- 24667120
TI  - Genome-wide association study identifies new disease loci for isolated clubfoot.
AB  - BACKGROUND: Clubfoot is a common congenital birth defect with complex inheritance
      patterns. Currently, the genetic and morphological basis of clubfoot is poorly
      understood. To identify genetic risk factors associated with clubfoot, we
      performed a genome-wide association study of common genetic variants. METHODS:
      The DNA of 396 isolated clubfoot patients and 1000 controls of European descent
      was genotyped for >600 000 single nucleotide polymorphisms (SNP) using the
      Affymetrix 6.0 array. Replication was performed with an independent cohort of 370
      isolated clubfoot cases and 363 controls of European descent. RESULTS: Strongest
      evidence for an association of clubfoot was found with an intergenic SNP on
      chromosome 12q24.31 between NCOR2 and ZNF664 (rs7969148, OR=0.58, p=1.25*10-5)
      that was significant on replication (combined OR=0.63, p=1.90*10-7). Additional
      suggestive SNPs were identified near FOXN3, SORCS1 and MMP7/TMEM123 that also
      confirmed on replication. CONCLUSIONS: Our study suggests a potential role for
      common genetic variation in several genes that have not previously been
      implicated in clubfoot pathogenesis.

PMID- 24667123
TI  - Influence of age on osteoarthritis progression after anterior cruciate ligament
      transection in rats.
AB  - The anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in
      young rats is widely used to study the pathogenesis of OA and possible treatment
      approaches. As aging is a key factor in the progression of this condition, it is
      hypothesized that animals may vary in their responses to ACLT according to their
      age. The histopathological features of young (2month-old) and middle-aged
      (12month-old) rats in the presence or absence of ACLT were compared. The results
      indicated that moderate degradative changes can be detected in the knee joints of
      sham-operated middle-aged rats compared with young animals. After ACLT, cartilage
      degradation was significantly higher in middle-aged rats in relation to young
      animals. An increase in interleukin(IL)-1beta and IL-17 suggests the presence of
      a local inflammatory response represented by synovitis in ACLT rats which is not
      dependent on age. Our study indicates that age is an important factor affecting
      the pathogenesis of OA changes after ACLT and it should be considered in studies
      using this experimental model. 

PMID- 24667124
TI  - Computational approaches to mapping allosteric pathways.
AB  - Allosteric signaling occurs when chemical and/or physical changes at an
      allosteric site alter the activity of a primary orthosteric site often many
      Angstroms distant. A number of recently developed computational techniques,
      including dynamical network analysis, novel topological and molecular dynamics
      methods, and hybrids of these methods, are useful for elucidating allosteric
      signaling pathways at the atomistic level. No single method prevails as best to
      identify allosteric signal propagation path(s), rather each has particular
      strengths in characterizing signals that occur over specific timescale ranges and
      magnitudes of conformational fluctuation. With continued improvement in accuracy
      and predictive power, these computational techniques aim to become useful drug
      discovery tools that will allow researchers to identify allostery critical
      residues for subsequent pharmacological targeting. 

PMID- 24667125
TI  - Predictive value of the complex magnetocardiographic index in patients with
      intermediate pretest probability of chronic coronary artery disease: results of a
      two-center study.
AB  - INTRODUCTION: The aim of this paper is to investigate the predictive value of the
      new integrated magnetocardiographic (MCG) index (CI) in the diagnosis of coronary
      artery disease (CAD) in patients with suspected CAD with intermediate pretest
      probability of the disease and uninformative results of routine tests. PATIENTS
      AND METHODS: The study was carried out in the Clinic of Cardiology of the Main
      Military Clinical Hospital of Ukraine, Kiev (clinic 1), and in the Second Medical
      Clinic of the 'Katholisches Klinikum Essen', Germany (clinic 2).The main group
      (group 1) included 89 patients without a history of myocardial infarction.
      Coronary angiography was performed because of chest pain. Depending on the
      results of coronary angiography, this group was divided into two subgroups: (i)
      those with at least 70% stenosis in at least one of the main coronary arteries
      (subgroup 1a) and (ii) those without hemodynamically significant stenosis
      (subgroup 1b). The control group included 43 healthy volunteers.In all
      participants, the MCG examination was performed using a seven-channel MCG system
      located in an unshielded room. An integrated MCG index (CI), consisting of six
      parameters, was calculated. RESULTS: It can be shown that CI was significantly
      higher in patients with stenosis 70% or more compared with the patients without
      stenosis and healthy volunteers. Sensitivity was 93%, specificity was 84%,
      positive predictive value was 85%, and negative predictive value was 93%.
      CONCLUSION: The MCG test at rest has the potential to be useful in the
      noninvasive diagnosis of CAD in patients with intermediate pretest probability of
      disease and uninformative results of routine tests.

PMID- 24667126
TI  - Long-term outcomes of patients with complex coronary artery disease according to
      agreement between the SYNTAX score and revascularization procedure in
      contemporary practice.
AB  - AIMS: The SYNTAX score (SS) has been shown to identify subgroups of patients with
      left main or triple-vessel coronary artery disease (LM/3VCAD) that can be treated
      with a percutaneous coronary intervention (PCI) with equal clinical outcomes as
      coronary artery bypass surgery (CABG).We sought to assess the adequacy of
      referral to PCI/CABG of patients with LM/3VCAD at our institution. PATIENTS AND
      METHODS: We retrospectively matched all patients with LM/3VCAD referred to CABG
      (n=145) to patients referred to PCI in our institution during 2009-2010. We
      calculated the SS and clinical SS (cSS) according to the European Society of
      Cardiology guidelines and compared the agreement rates between the
      revascularization modality and the SS as well as clinical outcomes at the 3-year
      follow-up. RESULTS: The overall agreement rates between the revascularization
      procedure and the SS was 67%, for example the rate was higher in patients
      referred to PCI compared with CABG (78 vs. 49%) and patients with 3VCAD compared
      with patients with LMCAD (68 vs. 51%). Patients without agreement between the
      revascularization modality and the SS had higher rates of combined adverse
      cardiac events (42.6 vs. 27% P=0.008). Similar results were observed when using
      the cSS at different cutoff levels. CONCLUSION: At our institution, there was
      considerable disagreement between a clinical judgment-based coronary
      revascularization and the SS/cSS-based allocation process as to the preferred
      revascularization modality for patients with complex CAD. Our results suggest
      that integrating the SS/cSS into the decision-making process for assigning
      patients to revascularization would yield better clinical outcomes.

PMID- 24667127
TI  - Determination of the severity of underlying lesions in acute myocardial
      infarction on the basis of collateral vessel development.
AB  - BACKGROUND: We aimed to address the conflict over whether the underlying lesion
      that leads to acute myocardial infarction (AMI) is representative of low-grade or
      high-grade stenosis. Because the development of collateral vessels is an
      indication of ischemia, their presence was used as a surrogate marker for the
      existence of a high-grade lesion. METHODS: Coronary angiography was used to
      assess 159 patients, divided into two groups, with (Rentrop 1-3) and without
      (Rentrop 0) collateral vessels, who had AMI with ST-segment elevation for which
      they underwent a percutaneous coronary intervention with the implantation of a
      coronary stent and had baseline thrombolysis in myocardial infarction 0/1 flow.
      RESULTS: Of the 159 patients recruited, the presence of collateral vessels was
      detected in 95 (collateral group; 60%), indicating that the causal lesion was
      representative of a high-grade stenosis. Among these 95 patients, the Rentrop
      scores were 1, 2, and 3 in 57 (60%), 33 (34.7%), and six (5.3%) patients,
      respectively. Logistic regression analysis showed that a baseline thrombolysis in
      myocardial infarction 0 flow (hazard ratio, 4.6; 95% confidence interval, 1.4
      14.6; P=0.01) and a culprit right coronary artery (hazard ratio, 3.0; 95%
      confidence interval, 1.4-6.2; P=0.007) were independent predictors of the
      development of collateral vessels. CONCLUSION: The majority of AMI cases can be
      attributed to a severe stenosis, as demonstrated by the presence of collateral
      vessels in 60% of the patients in this study.

PMID- 24667128
TI  - Inhibition of PCSK9: a novel approach for the treatment of dyslipidemia.
AB  - Hypercholesterolemia is a key risk factor for atherosclerosis. Because of its
      role in controlling serum levels of low-density lipoprotein (LDL) through the
      regulation of hepatic LDL-receptors, the recently discovered proprotein
      convertase subtilisin/kexin-type 9 (PCSK9) is a promising pharmacological target.
      This review aims to discuss the impact of natural mutations in the PCSK9 gene on
      cholesterol metabolism and thus coronary artery disease, as well as molecular
      mechanisms and therapeutic strategies for PCSK9 inhibition. We summarize data
      from recent clinical trials using fully humanized monoclonal antibodies, showing
      that PCSK9 inhibition results in a significant reduction in LDL-cholesterol in
      high-risk cardiovascular patients. Future studies will have to address the long
      term safety and efficacy as well as the impact of PCSK9-targeting therapies on
      cardiovascular outcomes. 

PMID- 24667129
TI  - Impaired testicular function after an ifosfamide-containing regimen for pediatric
      osteosarcoma: a case series and review of the literature.
AB  - To assess testicular function after standard dose ifosfamide, we evaluated 6
      young adult osteosarcoma survivors (median age at diagnosis, 16.5 y; median
      follow-up, 4 y) treated with ifosfamide (median dose, 45.5 g/m) as part of a
      chemotherapy regimen (adriamycin/cisplatin/methotrexate/ifosfamide/+/- muramyl
      tripeptide-phosphatidyl-ethanolamine). Four of 6 survivors (67%) had abnormal
      semen analysis (2 oligospermic, 2 azoospermic). Of those, 1/4 had reduced
      testicular volume, and 2/3 elevated FSH levels. All reported adequate sexual
      function, 6/6 had normal testosterone levels, but 4/6 had elevated LH levels.
      Ifosfamide exposure in the context of this regimen was associated with a high
      likelihood of impaired spermatogenesis and Leydig cell insufficiency.

PMID- 24667130
TI  - Therapeutic effect of polysaccharide of large yellow croaker swim bladder on
      lupus nephritis of mice.
AB  - The therapeutic effect of polysaccharide of large yellow croaker swim bladder
      (PLYCSB) on lupus nephritis has been studied in vivo. A high concentration (50
      mg/kg dose) of PLYCSB reduced the levels of serum inflammatory cytokine levels of
      IL-6, IL-12, TNF-alpha and IFN-gamma compared to a low concentration (25 mg/kg
      dose) and control mice. SCr, BUN, TC and TG serum levels of PLYCSB treated mice
      were lower than those of control mice, and TP and ALB serum levels were higher
      than control mice. Control mice tested ds-DNA positive at the 6th week, and 50
      mg/kg treated mice tested at the 10th week after the experiment began. The output
      of urine protein of 50 mg/kg PLYCSB treated mice was most closely comparable to
      the normal mice. The glomerular number of 50 mg/kg PLYCSB treated mice was more
      than the 25 mg/kg dose and control groups, and the 50 mg/kg dose group showed the
      lowest glomerular sclerosis index in lupus nephritis mice. By RT-PCR and western
      blot assay, PLYCSB significantly induced inflammation in kidney tissues of mice
      by downregulating NF-kappaB-p65, TGF-beta1, Fas, FasL and upregulating IkappaB
      alpha. These results suggest that PLYCSB showed a potential curative effect on
      lupus nephritis as a drug or functional food. 

PMID- 24667131
TI  - The role of hypertriglyceridemia in the development of atherosclerosis and
      endothelial dysfunction.
AB  - A hereditary postprandial hypertriglyceridemic rabbit (PHT rabbit) is a new
      dyslipidemic model showing remarkably high plasma triglycerides with only limited
      elevation of plasma total cholesterol. In PHT rabbits, plasma triglyceride was
      markedly elevated postprandially compared with healthy Japanese white (JW)
      rabbits. In physiological experiments, the ring preparation of the thoracic aorta
      was suspended in an organ bath filled with modified Krebs-Henseleit solution, and
      the developed tension was recorded. Endothelial function was evaluated by
      acetylcholine-induced vasorelaxation in each preparation with intact endothelium.
      The acetylcholine-induced endothelium-dependent relaxation was diminished in PHT
      compared with JW rabbits, suggesting endothelial dysfunction in PHT rabbits.
      Histological examination was carried out in adipose tissue, liver and aorta. They
      were fixed in formaldehyde and embedded in paraffin. The tissues were sliced (4
      MUm) and stained using hematoxylin-eosin solution. In the adipose tissue, the
      visceral fat accumulated, and the size of adipose cells was enlarged in PHT
      rabbits. The liver of the PHT rabbit was fatty and degenerated. In aorta,
      increased intimal thickness was observed, suggesting the progression of
      atherosclerosis in the PHT rabbit. This study suggests the important role of
      postprandial hypertriglyceridemia in atherosclerosis. By using PHT rabbits, the
      effects of hypertriglyceridemia on health and diseases could be evaluated
      precisely. 

PMID- 24667132
TI  - Selenium fortification of an Italian rice cultivar via foliar fertilization with
      sodium selenate and its effects on human serum selenium levels and on erythrocyte
      glutathione peroxidase activity.
AB  - Selenium food fortification could be a cost-effective strategy to counteract the
      inadequacy of selenium intake among the Italian population. In this study, the
      effect of foliar fertilization with sodium selenate of an Italian rice cultivar
      and the increase of serum selenium and of erythrocyte glutathione peroxidase
      (GPx) activity after intake of fortified rice, have been evaluated. The effect of
      foliar fertilization with sodium selenate (50 g Se/ha) vs. water was studied.
      Moreover, in a randomized, double-blind study, 10 healthy women supplemented
      their usual diet with a daily dose of 80 g of Se-enriched-rice and 10 matched
      women with 80 g of regular rice. Before, after 5 and 20 days of supplementation,
      serum Se and GPx-activity were evaluated. The mean selenium content in Se
      enriched-rice was 1.64 +/- 0.28 MUg/g, while in regular rice it was 0.36 +/- 0.15
      MUg/g (p < 0.001). A significant increase of serum Se and GPx-activity was
      observed only in the intervention group and only after 20 days. The results show
      that selenium fortification of rice can be achieved with foliar fertilization
      with sodium selenate and that the 20 days intake of this Se-enriched-rice
      increases the serum selenium levels and GPx-activity. 

PMID- 24667133
TI  - Metabolic interactions between vitamin A and conjugated linoleic acid.
AB  - Lipid-soluble molecules share several aspects of their physiology due to their
      common adaptations to a hydrophilic environment, and may interact to regulate
      their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA)
      is a fatty acid with a conjugated diene structure that is found in low
      concentrations in ruminant products and available as a nutritional supplement.
      CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and
      its sole specific circulating carrier protein retinol-binding protein (RBP or
      RBP4). However, the precise mechanism of this action has not been elucidated yet.
      Here, we provide a summary of the current knowledge in this specific area of
      research and speculate that retinol and CLA may compete for catabolic pathways
      modulated by the activity of PPAR-alpha and RXR heterodimer. We also present
      preliminary data that may position PPAR-alpha at the crossroads between the
      metabolism of lipids and vitamin A. 

PMID- 24667134
TI  - Impact of polyphenol antioxidants on cycling performance and cardiovascular
      function.
AB  - This investigation sought to determine if supplementation with polyphenol
      antioxidant (PA) improves exercise performance in the heat (31.5  degrees C, 55%
      RH) by altering the cardiovascular and thermoregulatory responses to exercise.
      Twelve endurance trained athletes ingested PA or placebo (PLAC) for 7 days.
      Consecutive days of exercise testing were performed at the end of the
      supplementation periods. Cardiovascular and thermoregulatory measures were made
      during exercise. Performance, as measured by a 10 min time trial (TT) following
      50 min of moderate intensity cycling, was not different between treatments (PLAC:
      292 +/- 33 W and PA: 279 +/- 38 W, p = 0.12). Gross efficiency, blood lactate,
      maximal neuromuscular power, and ratings of perceived exertion were also not
      different between treatments. Similarly, performance on the second day of
      testing, as assessed by time to fatigue at maximal oxygen consumption, was not
      different between treatments (PLAC; 377 +/- 117 s vs. PA; 364 +/- 128 s, p =
      0.61). Cardiovascular and thermoregulatory responses to exercise were not
      different between treatments on either day of exercise testing. Polyphenol
      antioxidant supplementation had no impact on exercise performance and did not
      alter the cardiovascular or thermoregulatory responses to exercise in the heat. 

PMID- 24667136
TI  - Comparison of nutritional quality of the vegan, vegetarian, semi-vegetarian,
      pesco-vegetarian and omnivorous diet.
AB  - The number of studies comparing nutritional quality of restrictive diets is
      limited. Data on vegan subjects are especially lacking. It was the aim of the
      present study to compare the quality and the contributing components of vegan,
      vegetarian, semi-vegetarian, pesco-vegetarian and omnivorous diets. Dietary
      intake was estimated using a cross-sectional online survey with a 52-items food
      frequency questionnaire (FFQ). Healthy Eating Index 2010 (HEI-2010) and the
      Mediterranean Diet Score (MDS) were calculated as indicators for diet quality.
      After analysis of the diet questionnaire and the FFQ, 1475 participants were
      classified as vegans (n = 104), vegetarians (n = 573), semi-vegetarians (n =
      498), pesco-vegetarians (n = 145), and omnivores (n = 155). The most restricted
      diet, i.e., the vegan diet, had the lowest total energy intake, better fat intake
      profile, lowest protein and highest dietary fiber intake in contrast to the
      omnivorous diet. Calcium intake was lowest for the vegans and below national
      dietary recommendations. The vegan diet received the highest index values and the
      omnivorous the lowest for HEI-2010 and MDS. Typical aspects of a vegan diet (high
      fruit and vegetable intake, low sodium intake, and low intake of saturated fat)
      contributed substantially to the total score, independent of the indexing system
      used. The score for the more prudent diets (vegetarians, semi-vegetarians and
      pesco-vegetarians) differed as a function of the used indexing system but they
      were mostly better in terms of nutrient quality than the omnivores. 

PMID- 24667137
TI  - Physical exercise protects myenteric neurons and reduces parasitemia in
      Trypanosoma cruzi infection.
AB  - To evaluate the parasitemia, nitrergic neurons, and cytokines in Trypanosoma
      cruzi-infected mice subjected to moderate physical exercise, forty male Swiss
      mice, 30days of age, were divided: Trained Control (TC), Trained Infected (TI),
      Sedentary Control (SC), and Sedentary Infected (SI). The moderate physical
      exercise program on a treadmill lasted 8weeks. Three days after completing the
      moderate physical exercise program, the TI and SI groups were inoculated with
      1300 blood trypomastigotes of the Y strain of T. cruzi, and parasitemia was
      evaluated from day 4 to day 22 after inoculation. After 75days of infection,
      cytokines were measured and colonic neurons were quantified using
      immunofluorescence to identify neuronal nitric oxide synthase (nNOS). The results
      were analyzed using analysis of variance - Tukey and Kruskal-Wallis tests, to 5%
      significance. Moderate physical exercise reduced the parasite peak on day 8 of
      infection and total parasitemia (p<0.05), contributed to survival of number of
      nNOS-immunoreactive neurons (p<0.01) and promoted neuronal hypertrophy of the
      neurons (p<0.05), increased the synthesis of tumor necrosis factor-alpha (p<0.01)
      and transforming growth factor-beta (p>0.05), providing beneficial effects to the
      host by acting on the immune system to preserve nitrergic neurons. 

PMID- 24667135
TI  - Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty
      acids, and perspectives for the natural combination of both in krill oil.
AB  - The consumption of marine fishes and general seafood has long been recommended by
      several medical authorities as a long-term nutritional intervention to preserve
      mental health, hinder neurodegenerative processes, and sustain cognitive
      capacities in humans. Most of the neurological benefits provided by frequent
      seafood consumption comes from adequate uptake of omega-3 and omega-6
      polyunsaturated fatty acids, n-3/n-6 PUFAs, and antioxidants. Optimal n-3/n-6
      PUFAs ratios allow efficient inflammatory responses that prevent the initiation
      and progression of many neurological disorders. Moreover, interesting in vivo and
      clinical studies with the marine antioxidant carotenoid astaxanthin (present in
      salmon, shrimp, and lobster) have shown promising results against free radical
      promoted neurodegenerative processes and cognition loss. This review presents the
      state-of-the-art applications of n-3/n-6 PUFAs and astaxanthin as nutraceuticals
      against neurodegenerative diseases associated with exacerbated oxidative stress
      in CNS. The fundamental "neurohormesis" principle is discussed throughout this
      paper. Finally, new perspectives for the application of a natural combination of
      the aforementioned anti-inflammatory and antioxidant agents (found in krill oil)
      are also presented herewith. 

PMID- 24667138
TI  - Immunologic treatments for precancerous lesions and uterine cervical cancer.
AB  - Development of HPV-associated cancers not only depends on efficient negative
      regulation of cell cycle control that supports the accumulation of genetic
      damage, but also relies on immune evasion that enable the virus to go undetected
      for long periods of time. In this way, HPV-related tumors usually present MHC
      class I down-regulation, impaired antigen-processing ability, avoidance of T-cell
      mediated killing, increased immunosuppression due to Treg infiltration and
      secrete immunosuppressive cytokines. Thus, these are the main obstacles that
      immunotherapy has to face in the treatment of HPV-related pathologies where a
      number of different strategies have been developed to overcome them including new
      adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV
      vaccines was proved extremely efficacious in pre-clinical models, its progression
      through clinical trials suffered poor responses in the initial trials. Later
      attempts seem to have been more promising, particularly against the well-defined
      precursors of cervical, anal or vulvar cancer, where the local immunosuppressive
      milieu is less active. This review focuses on the advances made in these fields,
      highlighting several new technologies (such as mRNA vaccine, plant-derived
      vaccine). The most promising immunotherapies used in clinical trials are also
      summarized, along with integrated strategies, particularly promising in
      controlling tumor metastasis and in eliminating cancer cells altogether.After the
      early promising clinical results, the development of therapeutic HPV vaccines
      need to be implemented and applied to the users in order to eradicate HPV
      associated malignancies, eradicating existing perception (after the effectiveness
      of commercial preventive vaccines) that we have already solved the problem. 

PMID- 24667139
TI  - MUC1: a multifaceted oncoprotein with a key role in cancer progression.
AB  - The transmembrane glycoprotein Mucin 1 (MUC1) is aberrantly glycosylated and
      overexpressed in a variety of epithelial cancers, and plays a crucial role in
      progression of the disease. Tumor-associated MUC1 differs from the MUC1 expressed
      in normal cells with regard to its biochemical features, cellular distribution,
      and function. In cancer cells, MUC1 participates in intracellular signal
      transduction pathways and regulates the expression of its target genes at both
      the transcriptional and post-transcriptional levels. This review highlights the
      structural and functional differences that exist between normal and tumor
      associated MUC1. We also discuss the recent advances made in the use of MUC1 as a
      biomarker and therapeutic target for cancer. 

PMID- 24667140
TI  - Acute hypoxia and exercise-induced blood oxidative stress.
AB  - Hypoxic exercise is characterized by workloads decrements. Because exercise and
      high altitude independently elicit redox perturbations, the study purpose was to
      examine hypoxic and normoxic steady-state exercise on blood oxidative stress.
      Active males (n = 11) completed graded cycle ergometry in normoxic (975 m) and
      hypoxic (3,000 m) simulated environments before programing subsequent matched
      intensity or workload steady-state trials. In a randomized counterbalanced
      crossover design, participants completed three 60-min exercise bouts to
      investigate the effects of hypoxia and exercise intensity on blood oxidative
      stress. Exercise conditions were paired as such; 60% normoxic VO(2)peak performed
      in a normoxic environment (normoxic intensity-normoxic environment, NI-NE), 60%
      hypoxic VO(2)peak performed in a normoxic environment (HI-NE), and 60% hypoxic
      VO(2)peak performed in a hypoxic environment (HI-HE). Blood plasma samples drawn
      pre (Pre), 0 (Post), 2 (2HR) and 4 (4HR) hr post exercise were analyzed for
      oxidative stress biomarkers including ferric reducing ability of plasma (FRAP),
      trolox equivalent antioxidant capacity (TEAC), lipid hydroperoxides (LOOH) and
      protein carbonyls (PCs). Repeated-measures ANOVA were performed, a priori
      significance of p <= .05. Oxygen saturation during the HI-HE trial was lower than
      NI-NE and HI-NE (p < .05). A Time * Trial interaction was present for LOOH (p =
      .013). In the HI-HE trial, LOOH were elevated for all time points post while PC
      (time; p = .001) decreased post exercise. As evidenced by the decrease in
      absolute workload during hypoxic VO(2)peak and LOOH increased during HI-HE versus
      normoxic exercise of equal absolute (HI-NE) and relative (NI-NE) intensities.
      Results suggest acute hypoxia elicits work decrements associated with post
      exercise oxidative stress.

PMID- 24667142
TI  - Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression
      in osteosarcoma.
AB  - BACKGROUND: Defects in Human Leukocyte Antigen (HLA) class I antigen expression
      and/or function in tumor cells have been extensively investigated, because of
      their potential role in the escape of tumor cells from T cell recognition and
      destruction. The researchers evaluated HLA class I expression in tumor tissue as
      a prognostic factor in osteosarcoma patients and as a predictor of their
      survival. This retrospective cohort study was conducted at the pathology
      laboratory of Ain Shams University Hospital, and Ain Shams University Specialized
      Hospital during the period between January 2009 and January 2012. METHODS: The
      researchers investigated HLA class I expression in primary osteosarcoma by
      immunohistochemistry using EMR8-5 mAbs. Furthermore, researchers evaluated the
      correlation between HLA class I expression and the clinicopathological status and
      outcome in formalin fixed paraffin embedded tissues from thirty six (36) patients
      with osteosarcoma. RESULTS: A high expression of HLA class I was detected in 18
      (50) % of tumor samples examined; while tumors with low or negative expression
      represented 9 (25%) cases each. Data indicate that the overall survival rate of
      patients with tumors highly expressing HLA class I was significantly higher than
      those with low or negative expression. CONCLUSION: Down-regulation of class I
      antigen expression is associated with features of aggressive disease and a poorer
      prognosis. Therefore, it is imperative to identify HLA as a prognostic factor at
      the time of diagnosis to detect chemotherapy-resistant tumors and to generate a
      modified treatment regimen. VIRTUAL SLIDES: The virtual slides for this article
      can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1159334857109547.

PMID- 24667141
TI  - Global phosphoproteomic profiling reveals distinct signatures in B-cell non
      Hodgkin lymphomas.
AB  - Deregulation of signaling pathways controlled by protein phosphorylation
      underlies the pathogenesis of hematological malignancies; however, the extent to
      which deregulated phosphorylation may be involved in B-cell non-Hodgkin lymphoma
      (B-NHL) pathogenesis is largely unknown. To identify phosphorylation events
      important in B-NHLs, we performed mass spectrometry-based, label-free,
      semiquantitative phosphoproteomic profiling of 11 cell lines derived from three B
      NHL categories: Burkitt lymphoma, follicular lymphoma, and mantle-cell lymphoma.
      In all, 6579 unique phosphopeptides, corresponding to 1701 unique phosphorylated
      proteins, were identified and quantified. The data are available via
      ProteomeXchange with identifier PXD000658. Hierarchical clustering highlighted
      distinct phosphoproteomic signatures associated with each lymphoma subtype.
      Interestingly, germinal center-derived B-NHL cell lines were characterized by
      phosphorylation of proteins involved in the B-cell receptor signaling. Of these
      proteins, phosphoprotein associated with glycosphingolipid-enriched microdomains
      1 (PAG1) was identified with the most phosphorylated tyrosine peptides in Burkitt
      lymphoma and follicular lymphoma. PAG1 knockdown resulted in perturbation of the
      tyrosine phosphosignature of B-cell receptor signaling components. Significantly,
      PAG1 knockdown increased cell proliferation and response to antigen stimulation
      of these germinal center-derived B-NHLs. These data provide a detailed annotation
      of phosphorylated proteins in human lymphoid cancer. Overall, our study revealed
      the utility of unbiased phosphoproteome interrogation in characterizing signaling
      networks that may provide insights into pathogenesis mechanisms in B-cell
      lymphomas. 

PMID- 24667144
TI  - Proteome responses to nitrate in bioethanol production contaminant Dekkera
      bruxellensis.
AB  - Dekkera bruxellensis is an industrially relevant yeast, especially in bioethanol
      production. The capacity of D. bruxellensis to assimilate nitrate can confer
      advantages of this yeast over Saccharomyces cerevisiae at industrial conditions.
      In the present work we present the consequences of nitrate assimilation, using
      ammonium as reference, to the proteomics of D. bruxellensis. Thirty-four protein
      spots were overproduced in nitrate medium and were identified by MS-TOF/TOF
      analysis and were putatively identified by using local Mascot software. Apart
      from the overexpression of genes of nitrate metabolism, ATP synthesis and PPP and
      TCA pathways previously reported, cultivation on nitrate induced overproduction
      of glycolytic enzymes, which corroborate the high energy demand and NADH
      availability for nitrate assimilation. Overproduction of alcohol dehydrogenase
      (Adh) protein was also observed. Proteomic profile of D. bruxellensis cultivated
      in nitrate and described in the present work agrees with the hypothesis of
      metabolic flux regulation, making available the energy in the form of NADH to
      support nitrate assimilation. This work contributes with an initial picture of
      proteins presenting differential accumulation in industrial contaminant yeast, in
      strict association with possible metabolic responses to nitrate as sole nitrogen
      source in cultivation medium. BIOLOGICAL SIGNIFICANCE: The present study
      investigated the gene expression at translational level of yeast D. bruxellensis
      for nitrate assimilation. This study corroborated with biological models that
      consider the ability to assimilate this nitrogen source confers advantages on
      this yeast during the fermentation process industry. However, larger studies are
      needed in this way as our group is investigating new proteins under LC-MS/MS
      approach. Together, these studies will help in understanding the operation of
      networks and cellular regulation of the process of assimilation of nitrogen
      sources for the D. bruxellensis, unravelling new aspects of the physiology of
      this yeast by proteomic analysis. This article is part of a Special Issue
      entitled: Environmental and structural proteomics.

PMID- 24667143
TI  - SWATHTM- and iTRAQ-based quantitative proteomic analyses reveal an overexpression
      and biological relevance of CD109 in advanced NSCLC.
AB  - To identify cancer-related proteins, we used isobaric tags in a relative and
      absolute quantitation (iTRAQ) proteomic approach and SWATHTM quantification
      approach to analyze the secretome of an isogenic pair of highly metastatic and
      low metastatic non-small-cell lung cancer (NSCLC) cell lines. In addition, we
      compared two groups of pooled serum samples (12 early-stage and 12 late-stage
      patients) to mine data for candidates screened by iTRAQ-labeled proteomic
      analysis. A total of 110 proteins and 71 proteins were observed to be
      significantly differentially expressed in the cell line secretome and NSCLC sera,
      respectively. Among these proteins, CD109 was found to be highly expressed in
      both the highly metastatic cell line secretome and the group of late-stage
      patients. A sandwich ELISA assay also demonstrated an elevation of serum CD109
      levels in individual NSCLC patients (n=30) compared with healthy subjects (n=19).
      Furthermore, CD109 displayed higher expression in lung cancer tissues compared
      with their matched noncancerous lung tissues (n=72). In addition, the knockdown
      of CD109 influenced several NSCLC cell bio-functions, for instance, depressing
      cell growth, affecting cell cycle phases. These phenomena suggest that CD109
      plays a critical role in NSCLC progression. BIOLOGICAL SIGNIFICANCE: We
      simultaneously applied two quantitative proteomic approaches-iTRAQ-labeling and
      SWATHTM-to analyze the secretome of metastatic cell lines, in order to explore
      the cancer-associated proteins in conditioned media. In this study, our results
      indicate that CD109 plays a critical role in non-small-cell lung cancer (NSCLC)
      progression, and is overexpressed in advanced NSCLC.

PMID- 24667145
TI  - Sensitivity and feeding efficiency of the black garden ant Lasius niger to sugar
      resources.
AB  - Carbohydrate sources such as plant exudates, nectar and honeydew represent the
      main source of energy for many ant species and contribute towards maintaining
      their mutualistic relationships with plants or aphid colonies. Here we
      characterise the sensitivity, feeding response curve and food intake efficiency
      of the aphid tending ant, Lasius niger for major sugars found in nectar, honeydew
      and insect haemolymph (i.e. fructose, glucose, sucrose, melezitose and
      trehalose). We found that sucrose concentrations - ranging from 0.1 to 2.5 M -
      triggered food acceptance by L.niger workers with their food intake efficiency
      being enhanced by sugar concentrations of 1M or higher at which points energy
      intake was maximised. The range of sucrose concentrations that elicit a feeding
      response by L. niger scouts thus overlaps with that of natural sugar resources.
      The response curves of feeding acceptance by scouts consistently increased with
      sugar concentration, except for trehalose which was disregarded by the ants. Ants
      are highly sensitive to sucrose and melezitose exhibiting low response
      thresholds. Sucrose, fructose and glucose share a same potential to act as
      phagostimulants as they had similar half feeding efficiency concentration values
      when expressed as the energetic content of sugar solution. Aphid-biosynthezised
      melezitose generated the highest sensitivity and phagostimulant potential. The
      feeding behavior of ants appears to be primarily regulated by the energy content
      of the food solution for the main sugars present in nectar and honeydew. However,
      feeding by scouts is also influenced by the informative value of individual
      sugars when it serves as a cue for the presence of aphid partners such as the
      aphid-biosynthesised melezitose.

PMID- 24667146
TI  - Cortex glial cells activation, associated with lowered mechanical thresholds and
      motor dysfunction, persists into adulthood after neonatal pain.
AB  - We investigated if changes in glial activity in cortical areas that process
      nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain
      was induced by repetitive needle prickling on the right paw, twice per day for 15
      days starting at birth. Wistar rats received either neonatal pain or tactile
      stimulation and were tested behaviorally for mechanical withdrawal thresholds of
      the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains
      from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX
      42) and the following cortical areas were analyzed for immunoreactivity density:
      prefrontal, anterior insular, anterior cingulated, somatosensory and motor
      cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180
      after neonatal pain when compared to controls. Neonatal pain animals showed
      increased density for both GFAP and MCP-1 staining, but not for OX-42, in all
      investigated cortical areas on both experimental times (P15 and P180). Painful
      stimuli in the neonatal period produced pain behaviors immediately after injury
      that persisted in adult life, and was accompanied by increase in the glial
      markers density in cortical areas that process and interpret pain. Thus, long
      lasting changes in cortical glial activity could be, at least in part,
      responsible for the persistent hyperalgesia in adult rats that suffered from
      neonatal pain. 

PMID- 24667147
TI  - Methamphetamine exposure during pregnancy at pharmacological doses produces
      neurodevelopmental and behavioural effects in rat offspring.
AB  - In recent years methamphetamine (MA) use has become more prevalent, and of
      particular concern is its growing popularity of MA among women of childbearing
      age. However, to date, studies examining MA effects on the developing offspring
      in laboratory animals are limited. Thus, the aim of this study was to determine
      if in utero MA exposure in rats at pharmacological doses can have a negative
      impact on neonatal neurodevelopment and behaviour. Pregnant Sprague-Dawley dams
      (n=10 dams/group) received MA (0, 0.625, 1.25, 2.5mg/kg) once daily via oral
      gavage from gestational day 7 to 21. Maternal body weight, food and water
      consumption were recorded daily. A range of standard neurodevelopment parameters
      was examined in the offspring during the neonatal period. There were no
      neurodevelopmental deficits observed with offspring exposed to 0.625mg/kg MA, in
      fact, there were enhancements of neurodevelopment in some parameters at this low
      dose. However, exposure to the 1.25mg/kg MA dose resulted in significant
      impairments in surface righting reflex and forelimb grip in both sexes. Exposure
      to the 2.5mg/kg MA dose resulted in a significant reduction in ano-genital
      distance in males, and in both sexes resulted in delayed fur appearance and eye
      opening, impairments in surface righting reflex and negative geotaxis, and a
      reduction in body length. In conclusion, this study demonstrates that
      pharmacologically relevant doses of MA can have profound dose-related effects on
      neonatal outcome. If extrapolated to the clinical scenario this will give cause
      for concern regarding the risks associated with this drug of abuse at relatively
      low doses. 

PMID- 24667148
TI  - Treatment of complex intercondylar humeral fractures in adolescents by open
      reduction and internal fixation through the transolecranon approach.
AB  - This is a review of six cases of complex intercondylar fractures of the humerus
      in adolescents, treated operatively through a transolecranon approach. Outcome
      was assessed by means of the Mayo Elbow score, the Disability of the Arm,
      Shoulder and Hand score, and the Oxford Elbow score. All patients reported 'good'
      to 'excellent' results. One patient required revision surgery because of fracture
      nonunion, and all patients underwent removal of hardware from the olecranon after
      osteotomy union. The transolecranon approach is effective in visualization of
      complex intercondylar fractures, and good outcomes are expected following stable
      surgical fixation in adolescents.

PMID- 24667149
TI  - Geometrically protected reversibility in hydrodynamic Loschmidt-echo experiments.
AB  - When periodically driven, a number of markedly different systems (colloids,
      droplets, grains, flux lines) have revealed a transition from a reversible to an
      irreversible dynamics that hardly depends on the very nature of the interacting
      objects. Yet, no clear structural signature has been found for this collective
      self-organization. Here, we demonstrate an archetypal Loschmidt-echo experiment
      involving thousands of droplets that interact in a reversible fashion via a
      viscous fluid. First, we show that periodically driven microfluidic emulsions
      self-organize and geometrically protect their macroscopic reversibility. Self
      organization is not merely dynamical: it has a clear structural signature.
      Second, we show that, above a maximal shaking amplitude, structural order and
      reversibility are lost simultaneously through a first-order non-equilibrium phase
      transition. We account for this discontinuous transition in terms of a memory
      loss process. Finally, we suggest potential applications of microfluidic echo as
      a robust tool to tailor colloidal self-assembly at large scales. 

PMID- 24667150
TI  - Representation and misrepresentation of scientific evidence in contemporary
      tobacco regulation: a review of tobacco industry submissions to the UK Government
      consultation on standardised packaging.
AB  - BACKGROUND: Standardised packaging (SP) of tobacco products is an innovative
      tobacco control measure opposed by transnational tobacco companies (TTCs) whose
      responses to the UK government's public consultation on SP argued that evidence
      was inadequate to support implementing the measure. The government's initial
      decision, announced 11 months after the consultation closed, was to wait for
      'more evidence', but four months later a second 'independent review' was
      launched. In view of the centrality of evidence to debates over SP and TTCs'
      history of denying harms and manufacturing uncertainty about scientific evidence,
      we analysed their submissions to examine how they used evidence to oppose SP.
      METHODS AND FINDINGS: We purposively selected and analysed two TTC submissions
      using a verification-oriented cross-documentary method to ascertain how published
      studies were used and interpretive analysis with a constructivist grounded theory
      approach to examine the conceptual significance of TTC critiques. The companies'
      overall argument was that the SP evidence base was seriously flawed and did not
      warrant the introduction of SP. However, this argument was underpinned by three
      complementary techniques that misrepresented the evidence base. First, published
      studies were repeatedly misquoted, distorting the main messages. Second,
      'mimicked scientific critique' was used to undermine evidence; this form of
      critique insisted on methodological perfection, rejected methodological
      pluralism, adopted a litigation (not scientific) model, and was not rigorous.
      Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence
      base to deflect attention from SP and excluding company-held evidence relevant to
      SP. The study's sample was limited to sub-sections of two out of four
      submissions, but leaked industry documents suggest at least one other company
      used a similar approach. CONCLUSIONS: The TTCs' claim that SP will not lead to
      public health benefits is largely without foundation. The tools of Better
      Regulation, particularly stakeholder consultation, provide an opportunity for
      highly resourced corporations to slow, weaken, or prevent public health policies.

PMID- 24667152
TI  - Fathers' child feeding practices: a review of the evidence.
AB  - Despite their expanding role in child rearing, fathers are underrepresented in
      child feeding research. To address this knowledge gap and encourage father
      focused research, this review compiles child feeding research that has included
      fathers and (i) documents characteristics of studies assessing fathers' feeding
      practices including study design, setting, recruitment strategies, participant
      characteristics, theoretical models utilized and measures of child feeding, (ii)
      outlines general patterns in fathers' feeding practices along with similarities
      and differences in mothers' and fathers' feeding practices, (iii) summarizes
      evidence on child and parent correlates of fathers' feeding practices and (iv)
      generates future research recommendations. A literature review of relevant
      articles published up to February 2014 was conducted. Studies were eligible for
      inclusion if they: (i) included fathers, or primary male caregivers, of children
      2-18 years of age, (ii) measured fathers' child feeding practices or perceived
      role in child feeding through objective (e.g., meal observations) or subjective
      (i.e., fathers' self-report) methods, (iii) analyzed and presented data on
      fathers separately from mothers and (iv) were published in a peer reviewed
      journal in the English language. Twenty studies met eligibility criteria. Few
      studies included an operational definition of "father". Samples were generally
      small and focused on white, well-educated fathers, cohabiting with the child's
      mother. Most studies utilized self-report measures of child feeding practices
      that have not been validated specifically for use with fathers. Pressuring
      children to eat was a common feeding strategy adopted by fathers. Some
      differences were noted in mothers' and fathers' feeding practices; fathers were
      generally less likely to monitor children's food intake and to limit access to
      food compared with mothers. Child adiposity and a range of child and parent
      characteristics were associated with fathers' feeding practices. The literature
      on fathers' child feeding practices is scant. This review consolidates what is
      known to date and highlights focal areas for future research including the need
      to recruit diverse samples of fathers and utilize measures validated for use with
      fathers. 

PMID- 24667151
TI  - Snail modulates the assembly of fibronectin via alpha5 integrin for myocardial
      migration in zebrafish embryos.
AB  - The Snail family member snail encodes a zinc finger-containing transcriptional
      factor that is involved in heart formation. Yet, little is known about how Snail
      regulates heart development. Here, we identified that one of the duplicated snail
      genes, snai1b, was expressed in the heart region of zebrafish embryos. Depletion
      of Snai1b function dramatically reduced expression of alpha5 integrin, disrupted
      Fibronectin layer in the heart region, especially at the midline, and prevented
      migration of cardiac precursors, resulting in defects in cardiac morphology and
      function in zebrafish embryos. Injection of alpha5beta1 protein rescued the
      Fibronectin layer and then the myocardial precursor migration in snai1b knockdown
      embryos. The results provide the molecular mechanism how Snail controls the
      morphogenesis of heart during embryonic development. 

PMID- 24667153
TI  - Effects of a price increase on purchases of sugar sweetened beverages. Results
      from a randomized controlled trial.
AB  - Sugar sweetened beverage (SSB) taxes are receiving increased political interest.
      However, there have been no experimental studies of the effects of price
      increases on SSBs or the effects on close substitutes such as diet drinks,
      alcohol or sugary snacks. Therefore, the aim of this study was to examine the
      effects of a price increase on SSBs on beverage and snack purchases using a
      randomized controlled design within a three-dimensional web-based supermarket.
      The trial contained two conditions: experimental condition with a 19% tax on SSBs
      (to reflect an increase in Dutch value added tax from 6% to 19%); and a control
      condition with regular prices. N = 102 participants were randomized and purchased
      groceries on a single occasion at a three-dimensional Virtual Supermarket. Data
      were analysed using independent t-tests and regression analysis. Results showed
      that participants in the price increase condition purchased significantly less
      SSBs than the control group (B = -.90; 95% CI = -1.70 to -.10 L per household per
      week). There were no significant effects on purchases in other beverage or snack
      food categories. This means that the higher VAT rate was effective in reducing
      SSB purchases and had no negative side-effects. 

PMID- 24667155
TI  - Disordered eating and eating disorders in aquatic sports.
AB  - Disordered eating behavior (DE) and eating disorders (EDs) are of great concern
      because of their associations with physical and mental health risks and, in the
      case of athletes, impaired performance. The syndrome originally known as the
      Female Athlete Triad, which focused on the interaction of energy availability,
      reproductive function, and bone health in female athletes, has recently been
      expanded to recognize that Relative Energy Deficiency in Sport (RED-S) has a
      broader range of negative effects on body systems with functional impairments in
      both male and female athletes. Athletes in leanness-demanding sports have an
      increased risk for RED-S and for developing EDs/DE. Special risk factors in
      aquatic sports related to weight and body composition management include the
      wearing of skimpy and tight-fitting bathing suits, and in the case of diving and
      synchronized swimming, the involvement of subjective judgments of performance.
      The reported prevalence of DE and EDs in athletic populations, including athletes
      from aquatic sports, ranges from 18 to 45% in female athletes and from 0 to 28%
      in male athletes. To prevent EDs, aquatic athletes should practice healthy eating
      behavior at all periods of development pathway, and coaches and members of the
      athletes' health care team should be able to recognize early symptoms indicating
      risk for energy deficiency, DE, and EDs. Coaches and leaders must accept that
      DE/EDs can be a problem in aquatic disciplines and that openness regarding this
      challenge is important. 

PMID- 24667154
TI  - Food consumption and weight gain after cessation of chronic amphetamine
      administration.
AB  - Cessation of drug use often coincides with increased food consumption and weight
      gain in recovering addicts. However, it is not known whether this phenomenon
      (particularly the weight gain) is uniquely human, or whether it represents a
      consequence of drug cessation common across species. To address this issue, rats
      (n = 10/group) were given systemic injections of D-amphetamine (3 mg/kg) or an
      equal volume of saline vehicle for 9 consecutive days. Beginning 2 days after the
      final injection, rats were given free access to a highly palatable food mixture
      (consisting of sugar and butter) along with their standard chow diet, and food
      consumption and body weight were measured every 48 h for 30 days. Consistent with
      clinical observations, amphetamine-treated rats showed a greater increase in body
      weight over the course of the 30 days relative to vehicle-treated rats.
      Surprisingly, there was no difference in highly palatable food consumption
      between amphetamine- and vehicle-treated groups, but the amphetamine-treated
      group consumed significantly more standard chow than the control group. The
      finding that a history of chronic amphetamine exposure increases food consumption
      is consistent with previous work in humans showing that withdrawal from drugs of
      abuse is associated with overeating and weight gain. The current findings may
      reflect amphetamine-induced sensitization of mechanisms involved in reward
      motivation, suggesting that weight gain following drug cessation in humans could
      be due to similar mechanisms. 

PMID- 24667156
TI  - Looking in the right direction: Carl Woese and evolutionary biology.
AB  - Carl Woese is known to the scientific community primarily through his landmark
      contributions to microbiology, in particular, his discovery of the third Domain
      of Life, which came to be known as the Archaea. While it is well known how he
      made this discovery, through the techniques he developed based on his studies of
      rRNA, the reasons why he was driven in this scientific direction, and what he saw
      as the principle outcome of his discovery--it was not the Archaea!--are not so
      widely appreciated. In this essay, I discuss his vision of evolution, one which
      transcends population genetics, and which has ramifications not only for our
      understanding of the origin of life on Earth and elsewhere, but also for our
      understanding of biology as a novel class of complex dynamical systems.

PMID- 24667157
TI  - Intramuscular Transplantation of Pig Amniotic Fluid-Derived Progenitor Cells Has
      Therapeutic Potential in a Mouse Model of Myocardial Infarction.
AB  - Acute myocardial infarction (MI) is a fatal event that causes a large number of
      deaths worldwide. MI results in pathological remodeling and decreased cardiac
      function, which could lead to heart failure and fatal arrhythmia. Cell therapy is
      a potential strategy to repair the damage through enhanced angiogenesis or by
      modulation of the inflammatory process via paracrine signaling. Amniotic fluid
      derived progenitor cells (AFPCs) have been reported to differentiate into several
      lineages and can be used without ethical concerns or risk of teratoma formation.
      Since pigs are anatomically, physiologically, and genetically similar to humans,
      and pregnant pigs can be an abundant source of AFPCs, we used porcine AFPCs
      (pAFPCs) as our target cells. Intramyocardial injection of AFPCs has been shown
      to cure MI in animal models. However, intramuscular transplantation of cells has
      not been extensively investigated. In this study, we investigated the therapeutic
      potential of intramuscular injection of pAFPCs on acute MI. MI mice were divided
      into 1) PBS control, 2) medium cell dose (1 * 10(6) cells per leg; cell-M), and
      3) high cell dose (4 * 10(6) cells per leg; cell-H) groups. Cells or PBS were
      directly injected into the hamstring muscle 20 min after MI surgery. Four weeks
      after MI surgery, the cell-M and cell-H groups exhibited significantly better
      ejection fraction, significantly greater wall thickness, smaller infarct scar
      sizes, and lower LV expansion index compared to the PBS group. Using in vivo
      imaging, we showed that the hamstring muscles from animals in the cell-M and cell
      H groups had RFP-positive signals. In summary, intramuscular injection of porcine
      AFPCs reduced scar size, reduced pathological remodeling, and preserved heart
      function after MI. 

PMID- 24667158
TI  - Therapeutic aphaeresis: experience in Puerto Rico.
AB  - The Puerto Rico (PR) Region of the American Red Cross (ARC) evaluated the
      therapeutic aphaeresis program and we conducted 1609 procedures in 30 months
      between 2011 and 2013. The primary objective of the present review was to
      demonstrate our data and compare it to the reviewed medical evidence regarding
      the adequacy of applying therapeutic aphaeresis (TA) for chosen indications based
      on data in the literature. It was concluded that our service is very active and
      appropriate, and the number of TA's done varies and it's not steady year-by-year.
      The indications are the same as most common indicators across the World and the
      adverse reactions are too. We are the only ones doing apheresis in the pediatric
      population of PR. No deaths have been reported from our procedures. We understand
      that clinicians do not have enough knowledge about TA and tend to apply TA's in
      many cases as a last resort treatment for many diseases. Education at medical
      faculties and of hospital staff (nurses and medical technologists) about TA is
      very important. There is a need for symposia about this topic to the medical and
      general community.

PMID- 24667159
TI  - Is Next Generation Sequencing the future of blood group testing?
AB  - Blood group genotyping has many advantages over conventional phenotyping for both
      blood donors and patients, and a number of high-throughput methods have now been
      developed. However, these are limited by a requirement for existing knowledge of
      the relevant blood group gene polymorphisms, and rare or novel mutations will not
      be detected. These mutations could be successfully identified by DNA sequencing
      of the blood group genes, and such an approach has been made feasible by the
      introduction of Next Generation Sequencing (NGS) technology. NGS enables many
      genes from multiple samples to be sequenced in parallel, resulting in sequencing
      information that could be used to obtain accurate blood group phenotype
      predictions in both blood donors and patients. 

PMID- 24667160
TI  - Successful management of thrombotic thrombocytopenic purpura associated with
      pregnancy.
AB  - Thrombotic thrombocytopenic purpura (TTP) is an uncommon, severe, potentially
      life-threatening disease characterized by microangiopathic hemolytic anemia,
      thrombocytopenia, altered mental status, fever, and renal abnormalities. It can
      be seen at any age or sex but affects women of childbearing age more commonly.
      Pregnancy is known as one of the most common precipitating events for the onset
      of TTP and occurs mostly in the late third trimester or during the puerperium.
      Because of relatively low prevalence of pregnancy-related TTP, here we report the
      clinical characteristics and successful outcomes of 7 women with pregnancy
      related TTP. Median age of patients was 25 (19-32). While 4 out of 7 women were
      primiparous, others were multiparous. Total plasma exchange (TPE) procedure was
      started within 24h after admission to our hospital. All patients got into
      complete remission without any maternal mortality. Fetal mortality was found to
      be 28%. Pregnancy-related TTP is still associated with high maternal and fetal
      mortality rates. However, the prognosis of TTP has improved dramatically with
      early diagnosis and plasma- based therapies. 

PMID- 24667161
TI  - Clinically meaningful effect of strontium ranelate on symptoms in knee
      osteoarthritis: a responder analysis.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of strontium
      ranelate in improving symptoms in knee OA. METHODS: Symptoms were assessed over 3
      years in patients with primary knee OA receiving strontium ranelate 2 g/day (n =
      454), 1 g/day (n = 445) or placebo (n = 472) in the Strontium Ranelate Efficacy
      in Knee Osteoarthritis Trial. Clinical response was evaluated using WOMAC
      subscores, minimal perceptible clinical improvement (MPCI), minimal clinically
      important improvement (MCII) and a modified OMERACT-Osteoarthritis Research
      Society International (OARSI) responder definition. Patients who withdrew
      prematurely from the study were considered non-responders. RESULTS: There was no
      significant effect on symptoms for strontium ranelate 1 g/day. At the dosage of 2
      g/day, strontium ranelate was associated with greater response than placebo in
      terms of >=20% improvement in WOMAC pain from baseline to the last visit (58% vs
      47%, P = 0.002) and >=50% improvement in WOMAC pain (42% vs 36%, P = 0.083).
      Significant differences were found in MPCI response for WOMAC pain (52% vs 40%, P
      < 0.001), stiffness (47% vs 39%, P = 0.009) and physical function (46% vs 37%, P
      = 0.009) and in MCII response for WOMAC physical function (46% vs 37%, P =
      0.013). There were also more OMERACT-OARSI-like responders with strontium
      ranelate (44% vs 35%, P = 0.004). The treatment-placebo difference in MPCI
      response for WOMAC pain was significant after 6 months (P = 0.024), while that in
      MPCI and MCII response for WOMAC physical function reached significance after 12
      months (P = 0.027 and P = 0.019, respectively). CONCLUSION: Treatment with
      strontium ranelate 2 g/day over 3 years is associated with a clinically
      meaningful improvement in pain from 6 months as well as physical function and
      stiffness as assessed by the number of responders above thresholds of clinical
      relevance. TRIAL REGISTRATION: Current Controlled Trials. http://www.controlled
      trials.com/ (ISRCTN41323372).

PMID- 24667162
TI  - Mesenchymal stem cells from rats with chronic kidney disease exhibit premature
      senescence and loss of regenerative potential.
AB  - Mesenchymal stem cell (MSC) transplantation has the potential for organ repair.
      Nevertheless, some factors might lessen the regenerative potential of MSCs, e.g.
      donor age or systemic disease. It is thus important to carefully assess the
      patient's suitability for autologous MSC transplantation. Here we investigated
      the effects of chronic kidney disease (CKD) on MSC function. We isolated bone
      marrow MSCs from remnant kidney rats (RK) with CKD (CKD-RK-MSC) and found signs
      of premature senescence: spontaneous adipogenesis, reduced proliferation
      capacity, active senescence-associated-beta-galactosidase, accumulation of actin
      and a modulated secretion profile. The functionality of CKD-RK-MSCs in vivo was
      tested in rats with acute anti-Thy1.1-nephritis, where healthy MSCs have been
      shown to be beneficial. Rats received healthy MSCs, CKD-RK-MSC or medium by
      injection into the left renal artery. Kidneys receiving healthy MSCs exhibited
      accelerated healing of glomerular lesions, whereas CKD-RK-MSC or medium exerted
      no benefit. The negative influence of advanced CKD/uremia on MSCs was confirmed
      in a second model of CKD, adenine nephropathy (AD). MSCs from rats with adenine
      nephropathy (CKD-AD-MSC) also exhibited cellular modifications and functional
      deficits in vivo. We conclude that CKD leads to a sustained loss of in vitro and
      in vivo functionality in MSCs, possibly due to premature cellular senescence.
      Considering autologous MSC therapy in human renal disease, studies identifying
      uremia-associated mechanisms that account for altered MSC function are urgently
      needed. 

PMID- 24667163
TI  - Association between drug insurance cost sharing strategies and outcomes in
      patients with chronic diseases: a systematic review.
AB  - BACKGROUND: Prescription drugs are used in people with hypertension, diabetes,
      and cardiovascular disease to manage their illness. Patient cost sharing
      strategies such as copayments and deductibles are often employed to lower
      expenditures for prescription drug insurance plans, but the impact on health
      outcomes in these patients is unclear. OBJECTIVE: To determine the association
      between drug insurance and patient cost sharing strategies on medication
      adherence, clinical and economic outcomes in those with chronic diseases (defined
      herein as diabetes, hypertension, hypercholesterolemia, coronary artery disease,
      and cerebrovascular disease). METHODS: Studies were included if they examined
      various cost sharing strategies including copayments, coinsurance, fixed
      copayments, deductibles and maximum out-of-pocket expenditures. Value-based
      insurance design and reference based pricing studies were excluded. Two reviewers
      independently identified original intervention studies (randomized controlled
      trials, interrupted time series, and controlled before-after designs). MEDLINE,
      EMBASE, Cochrane Library, CINAHL, and relevant reference lists were searched
      until March 2013. Two reviewers independently assessed studies for inclusion,
      quality, and extracted data. Eleven studies, assessing the impact of seven policy
      changes, were included: 2 separate reports of one randomized controlled trial, 4
      interrupted time series, and 5 controlled before-after studies. FINDINGS:
      Outcomes included medication adherence, clinical events (myocardial infarction,
      stroke, death), quality of life, healthcare utilization, or cost. The
      heterogeneity among the studies precluded meta-analysis. Few studies reported the
      impact of cost sharing strategies on mortality, clinical and economic outcomes.
      The association between patient copayments and medication adherence varied across
      studies, ranging from no difference to significantly lower adherence, depending
      on the amount of the copayment. CONCLUSION: Lowering cost sharing in patients
      with chronic diseases may improve adherence, but the impact on clinical and
      economic outcomes is uncertain.

PMID- 24667164
TI  - Enzymatic and metabolic engineering for efficient production of syringin, sinapyl
      alcohol 4-O-glucoside, in Arabidopsis thaliana.
AB  - To promote efficient production of syringin, a plant-derived bioactive monolignol
      glucoside, synergistic effects of enzymatic and metabolic engineering were
      combined. Recombinant UGT72E3/E2 chimeras, generated by exchanging parts of the C
      terminal domain including the Putative Secondary Plant Glycosyltransferase (PSPG)
      motif of UGT72E3 and UGT72E2, were expressed in leaves of transgenic Arabidopsis
      plants; syringin production was measured in vivo and by enzymatic assays in
      vitro. In both tests, UGT72E3/2 displayed substrate specificity for sinapyl
      alcohol like the parental enzyme UGT72E3, and the syringin production was
      significantly increased compared to UGT72E3. In particular, in the in vitro
      assay, which was performed in the presence of a high concentration of sinapyl
      alcohol, the production of syringin by UGT72E3/2 was 4-fold higher than by
      UGT72E3. Furthermore, to enhance metabolic flow through the phenylpropanoid
      pathway and maintain a high basal concentration of sinapyl alcohol in the leaves,
      UGT72E3/2 was combined with the sinapyl alcohol synthesis pathway gene F5H
      encoding ferulate 5-hydroxylase and the lignin biosynthesis transcriptional
      activator MYB58. The resulting UGT72E3/2+F5H+MYB58 OE plants, which
      simultaneously overexpress these three genes, accumulated a 56-fold higher level
      of syringin in their leaves than wild-type plants. 

PMID- 24667165
TI  - Scale evolution, sequence phylogeny, and taxonomy of thaumatomonad Cercozoa: 11
      new species and new genera Scutellomonas, Cowlomonas, Thaumatospina and
      Ovaloplaca.
AB  - We describe 11 new species of Thaumatomonadida using light and electron
      microscopy and rDNA gene sequences (18S, ITS1, 5.8S, ITS2). We found clear
      distinctions between major clades in molecular and morphological traits that
      support now splitting Thaumatomastix into three genera: new marine genera
      Ovaloplaca (oval plate-scales) and Thaumatospina (triangular plate-scales), both
      with distinctive radially-symmetric bobbin-based spine-scales, restricting
      Thaumatomastix to freshwater species with putatively non-homologous eccentric
      spine scales and thicker triangular plate-scales. New genus Scutellomonas lacks
      spine-scales, having oval plate-scales with deeply-dished upper tier as in
      Ovaloplaca, with which it forms a clade having short/absent anterior cilium.
      Cowlomonas gen. n. is possibly naked. We describe two new Allas species, two new
      Thaumatomonas, and one new Reckertia species, and transfer R. hindoni to
      Thaumatomonas. Triangular-scaled Reckertia has varied plate-scales and ciliary
      scales. Thaumatomonas rDNA trees reveal two clades: zhukovi/seravini
      (predominantly triangular scales);
      coloniensis/oxoniensis/lauterborni/constricta/solis (scales mostly oval). We
      hypothesise that the ancestor of Thaumatomonadidae had radially-symmetric bobbin
      based spine-scales and triangular plate-scales, bobbin-based spine-scales being
      lost in one lineage and eccentric-spine scales evolving in Thaumatomastix. Bobbin
      based spine-scales arguably evolved from triangular plate-scales and single-tier
      ciliary scales (Ovaloplaca and Reckertia only) from plate-scale rudiments. We
      present a unified scheme for scale evolution and development in Imbricatea. 

PMID- 24667166
TI  - Memory and mood during MDMA intoxication, with and without memantine
      pretreatment.
AB  - Previous studies have shown that single doses of MDMA can affect mood and impair
      memory in humans. The neuropharmacological mechanisms involved in MDMA-induced
      memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic
      acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory
      impairment in rats. This study investigated whether treatment with memantine can
      prevent MDMA-induced memory impairment in humans. 15 subjects participated in a
      double-blind, placebo controlled, within-subject design. Subjects received both
      pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg)
      (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was
      assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective
      Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning
      Task. Profile of Mood State and psychomotor performance were also assessed to
      control whether MDMA and memantine interactions would selectively pertain to
      memory or transfer to other domains as well. MDMA significantly impaired
      performance in the visual verbal learning task and abstract visual pattern
      learning task. Pre-treatment with memantine did not prevent MDMA-induced memory
      impairment in these two tasks. Both positive (vigour, arousal, elation) and
      negative mood effects (anxiety) were increased by MDMA. The responses were not
      altered by pretreatment with memantine which had no effect on memory or mood when
      given alone. These preliminary results suggest that memantine does not reverse
      MDMA-induced memory impairment and mood in humans. This article is part of the
      Special Issue entitled 'CNS Stimulants'.

PMID- 24667167
TI  - Reperfusion promotes mitochondrial biogenesis following focal cerebral ischemia
      in rats.
AB  - BACKGROUND AND PURPOSE: Reperfusion after transient cerebral ischemia causes
      severe damage to mitochondria; however, little is known regarding the continuous
      change in mitochondrial biogenesis during reperfusion. Mitochondrial biogenesis
      causes an increase in the individual mitochondrial mass of neurons and maintains
      their aerobic set-point in the face of declining function. The aim of this study
      was to examine mitochondrial biogenesis in the cortex during reperfusion
      following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to
      transient focal cerebral ischemia. The relative amount of cortical mitochondrial
      DNA was analyzed using quantitative real-time PCR at 0 h, 24 h, 72 h, and 7 d
      after reperfusion. Three critical transcriptional regulators of mitochondrial
      biogenesis were measured by semi-quantitative reverse-transcription PCR. The
      protein expression of cytochrome C oxidase subunits I and IV was detected by
      Western blotting. RESULTS: Evidence of increased mitochondrial biogenesis was
      observed after reperfusion. The cortical mitochondrial DNA content increased
      after 24 h, peaked after 72 h, and maintained a high level for 7 d. The cortical
      expression of three critical genes for the transcriptional regulation of
      mitochondrial biogenesis, namely, peroxisome proliferator-activated receptor
      coactivator-1alpha, nuclear respiratory factor-1, and mitochondrial transcription
      factor A, also increased at 24 h and 72 h. The expression of peroxisome
      proliferator-activated receptor coactivator-1alpha returned to the baseline level
      at 7 d, but two other factors maintained higher levels compared with the
      controls. Moreover, the expression of cytochrome C oxidase subunits I and IV was
      increased in the cortex. CONCLUSIONS: These results indicate that reperfusion
      increased mitochondrial biogenesis following focal cerebral ischemia, and this
      tendency was exacerbated as the reperfusion time was extended. Reperfusion
      induced mitochondrial biogenesis was mediated through up-regulation of critical
      transcriptional regulators of mitochondrial biogenesis.

PMID- 24667169
TI  - Low-intensity pulsed ultrasound in lower limb bone stress injuries: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of low-intensity pulsed ultrasound
      (LIPUS) for the improvement of lower limb bone stress injuries in a civilian
      population. DESIGN: A prospective, randomized, double-blinded, placebo-controlled
      trial to compare LIPUS with placebo. SETTING: Civilian private practice
      population in Sydney, Australia. PARTICIPANTS: Subjects were recruited if a grade
      II-IV bone stress injury was diagnosed on magnetic resonance imaging (MRI) of
      either the postero-medial tibia, fibula or second, third, or fourth metatarsal.
      Subjects of all levels of sporting activity were included. Thirty subjects were
      initially recruited, and 23 subjects were included in the final analysis.
      INTERVENTIONS: Subjects were randomized into either the treatment or placebo arm
      and matched to the site of injury (tibia, fibula, or metatarsal). Subjects in
      both arms used either treatment or placebo devices for 20 minutes daily for 4
      weeks. MAIN OUTCOME MEASURES: Six clinical parameters (night pain, pain at rest,
      pain on walking, pain with running, tenderness, and pain with single leg hop)
      were compared before and after intervention. The changes in MRI grade and bone
      marrow edema size were also compared. RESULTS: There were no significant
      differences between the treatment and placebo conditions for changes in MRI
      grading (2.2 vs 2.4, P = 0.776) or bone marrow edema size (3 vs 4.1, P = 0.271).
      There were no significant differences between the treatment and placebo
      conditions for the 6 clinical parameters. CONCLUSIONS: Low-intensity pulsed
      ultrasound was found not to be an effective treatment for the healing of lower
      limb bone stress injuries in this study. However, this was measured over a
      relatively short duration of 4 weeks in a small, mostly female population.
      CLINICAL RELEVANCE: This double-blinded, randomized, placebo-controlled trial has
      shown that LIPUS is not an effective treatment for lower limb bone stress
      injuries.

PMID- 24667168
TI  - Low 2012-13 influenza vaccine effectiveness associated with mutation in the egg
      adapted H3N2 vaccine strain not antigenic drift in circulating viruses.
AB  - BACKGROUND: Influenza vaccine effectiveness (VE) is generally interpreted in the
      context of vaccine match/mismatch to circulating strains with evolutionary drift
      in the latter invoked to explain reduced protection. During the 2012-13 season,
      however, detailed genotypic and phenotypic characterization shows that low VE was
      instead related to mutations in the egg-adapted H3N2 vaccine strain rather than
      antigenic drift in circulating viruses. METHODS/FINDINGS: Component-specific VE
      against medically-attended, PCR-confirmed influenza was estimated in Canada by
      test-negative case-control design. Influenza A viruses were characterized
      genotypically by amino acid (AA) sequencing of established haemagglutinin (HA)
      antigenic sites and phenotypically through haemagglutination inhibition (HI)
      assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell
      passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted
      strain as per actually used in vaccine production. Among the total of 1501
      participants, influenza virus was detected in 652 (43%). Nearly two-thirds of
      viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were
      A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%).
      Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2
      activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI
      characterized as well-matched to the WHO-recommended A/Victoria/361/2011
      prototype whereas all but one were antigenically distinct from the egg-adapted
      strain as per actually used in vaccine production. The egg-adapted strain was
      itself antigenically distinct from the WHO-recommended prototype, and bore three
      AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely,
      circulating viruses were identical to the WHO-recommended prototype at these
      positions with other genetic variation that did not affect antigenicity. VE was
      59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata
      (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine
      lineage) viruses. CONCLUSIONS: These findings underscore the need to monitor
      vaccine viruses as well as circulating strains to explain vaccine performance.
      Evolutionary drift in circulating viruses cannot be regulated, but influential
      mutations introduced as part of egg-based vaccine production may be amenable to
      improvements.

PMID- 24667171
TI  - Mycobacterium abscessus MAB2560 induces maturation of dendritic cells via Toll
      like receptor 4 and drives Th1 immune response.
AB  - In this study, we showed that Mycobacterium abscessus MAB2560 induces the
      maturation of dendritic cells (DCs), which are representative antigen-presenting
      cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory
      cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-1beta, and
      IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using TLR4-/-
      DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4
      (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential
      for DC maturation. Furthermore, MAB2560- treated DCs induced the transformation
      of naive T cells to polarized CD4+ and CD8+ T cells, which would be crucial for
      Th1 polarization of the immune response. Taken together, our results indicate
      that MAB2560 could potentially regulate the host immune response to M. abscessus
      and may have critical implications for the manipulation of DC functions for
      developing DC-based immunotherapy.

PMID- 24667170
TI  - Polo-like kinase-1 in DNA damage response.
AB  - Polo-like kinase-1 (Plk1) belongs to a family of serine-threonine kinases and
      plays a critical role in mitotic progression. Plk1 involves in the initiation of
      mitosis, centrosome maturation, bipolar spindle formation, and cytokinesis, well
      reported as traditional functions of Plk1. In this review, we discuss the role of
      Plk1 during DNA damage response beyond the functions in mitotsis. When DNA is
      damaged in cells under various stress conditions, the checkpoint mechanism is
      activated to allow cells to have enough time for repair. When damage is repaired,
      cells progress continuously their division, which is called checkpoint recovery.
      If damage is too severe to repair, cells undergo apoptotic pathway. If damage is
      not completely repaired, cells undergo a process called checkpoint adaptation,
      and resume cell division cycle with damaged DNA. Plk1 targets and regulates many
      key factors in the process of damage response, and we deal with these subjects in
      this review.

PMID- 24667172
TI  - Stathmin 1 in normal and malignant hematopoiesis.
AB  - Stathmin 1 is a microtubule destabilizer that plays an important role in cell
      cycle progression, segregation of chromosomes, clonogenicity, cell motility and
      survival. Stathmin 1 overexpression has been reported in malignant hematopoietic
      cells and Stathmin 1 inhibition reduces the highly proliferative potential of
      leukemia cell lines. However, during the differentiation of primary hematopoietic
      cells, Stathmin 1 expression decreases in parallel to decreases in the
      proliferative potential of early hematopoietic progenitors. The scope of the
      present review is to survey the current knowledge and highlight future
      perspectives for Stathmin 1 in normal and malignant hematopoiesis, with regard to
      the expression, function and clinical implications of this protein.

PMID- 24667173
TI  - Proteomic analysis of differentially expressed skin proteins in iRhom2(Uncv)
      mice.
AB  - A mouse homozygous for the spontaneous mutation uncovered (Uncv) has a hairless
      phenotype. A 309-bp non-frameshift deletion mutation in the N-terminal
      cytoplasmic domain of iRhom2 was identified in Uncv mice (iRhom2(Uncv)) using
      target region sequencing. The detailed molecular basis for how the iRhom2
      mutation causes the hairless phenotype observed in the homozygous iRhom2(Uncv)
      mouse remains unknown. To identify differentially expressed proteins in the skin
      of wild-type and homozygous iRhom2(Uncv) littermates at postnatal day 5,
      proteomic approaches, including two-dimensional gel electrophoresis and mass
      spectrometry were used. Twelve proteins were differentially expressed in the skin
      in a comparison between wild-type and homozygous iRhom2(Uncv) mice. A selection
      of the proteomic results were tested and verified using qRT-PCR, western blot and
      immunohistochemistry. These data indicate that differentially expressed proteins,
      especially KRT73, MEMO1 and Coro-1, might participate in the mechanism by which
      iRhom2 regulates the development of murine skin.

PMID- 24667174
TI  - Synergistic effect of two E2 ubiquitin conjugating enzymes in SCF(hFBH1)
      catalyzed polyubiquitination.
AB  - Ubiquitination is a post translational modification which mostly links with
      proteasome dependent protein degradation. This process has been known to play
      pivotal roles in the number of biological events including apoptosis, cell
      signaling, transcription and translation. Although the process of ubiquitination
      has been studied extensively, the mechanism of polyubiquitination by multi
      protein E3 ubiquitin ligase, SCF complex remains elusive. In the present study,
      we identified UbcH5a as a novel stimulating factor for poly-ubiquitination
      catalyzed by SCF(hFBH1) using biochemical fractionations and MALDI-TOF. Moreover,
      we showed that recombinant UbcH5a and Cdc34 synergistically stimulate SCF(hFBH1)
      catalyzed polyubiquitination in vitro. These data may provide an important cue to
      understand the mechanism how the SCF complex efficiently polyubiquitinates target
      substrates.

PMID- 24667175
TI  - Celastrol inhibits gastric cancer growth by induction of apoptosis and autophagy.
AB  - Recently, the interest in natural products for the treatment of cancer is
      increasing because they are the pre-screened candidates. In the present study, we
      demonstrate the therapeutic effect of celastrol, a triterpene extracted from the
      root bark of Chinese medicine on gastric cancer. The proliferation of AGS and YCC
      2 cells were most sensitively decreased in six kinds of gastric cancer cell lines
      after the treatment with celastrol. Celastrol inhibited the cell migration and
      increased G1 arrest in cell-cycle populations in both cell lines. The treatment
      with celastrol significantly induced autophagy and apoptosis and increased the
      expression of autophagy and apoptosis-related proteins. We also found an increase
      in phosphorylated AMPK following a decrease in all phosphorylated forms of AKT,
      mTOR and S6K after the treatment with celastrol. Moreover, gastric tumor burdens
      were reduced in a dose-dependent manner by celastrol administration in a
      xenografted mice model. Taken together, celastrol distinctly inhibits the gastric
      cancer cell proliferation and induces autophagy and apoptosis.

PMID- 24667176
TI  - Association study of newly identified age-related macular degeneration
      susceptible loci SOD2, MBP, and C8orf42 in Han Chinese population.
AB  - A recent genome-wide association study has reported three newly identified
      susceptible loci (rs2842992 near the gene SOD2, rs1789110 near the gene MBP and
      rs722782 near the gene C8orf42) to be associated with the geographic atrophy
      subtype of age-related macular degeneration in European-descent population. We
      investigated the correlation between these variants and advanced age-related
      macular degeneration for the first time in a Han Chinese cohort; however, no
      evidence supports these previously identified loci contribute to advanced age
      related macular degeneration susceptibility in Chinese population. 

PMID- 24667177
TI  - TBL1XR1 promotes lymphangiogenesis and lymphatic metastasis in esophageal
      squamous cell carcinoma.
AB  - OBJECTIVE: Transducin (beta)-like 1 X-linked receptor 1 (TBL1XR1) plays an
      important role in controlling the precisely regulated switch between gene
      repression and gene activation in transcriptional regulation. We investigated its
      biological function and clinical significance in esophageal squamous cell
      carcinoma (ESCC). DESIGN: Immunoblotting and immunochemistry were used to
      determine TBL1XR1 expression in ESCC cell lines, ESCC clinical tissues and 230
      clinicopathologically characterised ESCC specimens. The role of TBL1XR1 in
      lymphangiogenesis and lymphatic metastasis was examined by tube formation, cell
      invasion and wound-healing assays in vitro, and by a popliteal lymph node
      metastasis model in vivo. The molecular mechanism by which TBL1XR1 upregulates
      vascular endothelial growth factor C (VEGF-C) expression was explored using real
      time PCR, ELISA, luciferase reporter assay and chromatin immunoprecipitation.
      RESULTS: TBL1XR1 expression was significantly upregulated in ESCC, positively
      correlated with disease stage and patient survival, and identified as an
      independent prognostic factor for patient outcome. We found that TBL1XR1
      overexpression promoted lymphangiogenesis and lymphatic metastasis in ESCC in
      vitro and in vivo, whereas TBL1XR1 silencing had the converse effect. We
      demonstrated that TBL1XR1 induced VEGF-C expression by binding to the VEGF-C
      promoter. We confirmed the correlation between TBL1XR1 and VEGF-C expression in a
      large cohort of clinical ESCC samples and through analysis of published datasets
      in gastric, colorectal and breast cancer. CONCLUSIONS: Our results demonstrated
      that TBL1XR1 induced lymphangiogenesis and lymphatic metastasis in ESCC via
      upregulation of VEGF-C, and may represent a novel prognostic biomarker and
      therapeutic target for patients with ESCC.

PMID- 24667178
TI  - Chaos and robustness in a single family of genetic oscillatory networks.
AB  - Genetic oscillatory networks can be mathematically modeled with delay
      differential equations (DDEs). Interpreting genetic networks with DDEs gives a
      more intuitive understanding from a biological standpoint. However, it presents a
      problem mathematically, for DDEs are by construction infinitely-dimensional and
      thus cannot be analyzed using methods common for systems of ordinary differential
      equations (ODEs). In our study, we address this problem by developing a method
      for reducing infinitely-dimensional DDEs to two- and three-dimensional systems of
      ODEs. We find that the three-dimensional reductions provide qualitative
      improvements over the two-dimensional reductions. We find that the reducibility
      of a DDE corresponds to its robustness. For non-robust DDEs that exhibit high
      dimensional dynamics, we calculate analytic dimension lines to predict the
      dependence of the DDEs' correlation dimension on parameters. From these lines, we
      deduce that the correlation dimension of non-robust DDEs grows linearly with the
      delay. On the other hand, for robust DDEs, we find that the period of oscillation
      grows linearly with delay. We find that DDEs with exclusively negative feedback
      are robust, whereas DDEs with feedback that changes its sign are not robust. We
      find that non-saturable degradation damps oscillations and narrows the range of
      parameter values for which oscillations exist. Finally, we deduce that natural
      genetic oscillators with highly-regular periods likely have solely negative
      feedback. 

PMID- 24667179
TI  - Procollagen type 1 amino-terminal propeptide (P1NP) and risk of hip fractures in
      elderly Norwegian men and women. A NOREPOS study.
AB  - The current study aimed to assess a possible association between the bone
      turnover marker procollagen type 1 amino-terminal propeptide (P1NP) and future
      hip fractures in elderly Norwegian men and women and to elucidate the relation
      between P1NP, bone mineral density and 25-hydroxyvitamin D (25(OH)D). Men and
      women aged 71 to 77 from two population based health studies in Norway (1999
      2001) were followed for a median period of 7.3 years with respect to hip
      fractures. The study was designed as a case-cohort study. P1NP and 25(OH)D were
      analysed in frozen serum samples obtained at baseline in hip fracture patients
      (n=340) and in randomly selected sex stratified sub-cohorts. Bone mineral density
      was measured by dual-energy X-ray absorptiometry (DXA) in a subset of
      participants. Cox proportional hazards regression with inverse probability
      weighting and robust variance was performed. No significant correlation between
      25(OH)D and P1NP was found. A negative correlation between P1NP and BMD was
      observed in women (Rho=-0.36, p=0.001). A similar trend was observed in men. No
      association between quartiles of P1NP and rate of subsequent hip fractures was
      found. Spline analyses suggested a higher rate of hip fracture at P1NP levels
      above 60 MUg/L in both men and women. A higher hip fracture rate, which was
      independent of BMD, was also indicated in women with very low levels of P1NP.

PMID- 24667181
TI  - Underwater births should be limited to clinical trials, says US pediatric and
      obstetrics panel.

PMID- 24667180
TI  - Can senior volunteers deliver reminiscence and creative activity interventions?
      Results of the legacy intervention family enactment randomized controlled trial.
AB  - CONTEXT: Palliative care patients and their family caregivers may have a
      foreshortened perspective of the time left to live, or the expectation of the
      patient's death in the near future. Patients and caregivers may report distress
      in physical, psychological, or existential/spiritual realms. OBJECTIVES: To
      conduct a randomized controlled trial examining the effectiveness of retired
      senior volunteers (RSVs) in delivering a reminiscence and creative activity
      intervention aimed at alleviating palliative care patient and caregiver distress.
      METHODS: Of the 45 dyads that completed baseline assessments, 28 completed
      postintervention and 24 completed follow-up assessments. The intervention group
      received three home visits by RSVs; control group families received three
      supportive telephone calls by the research staff. Measures included symptom
      assessment and associated burden, depression, religiousness/spirituality, and
      meaning in life. RESULTS: Patients in the intervention group reported a
      significantly greater reduction in frequency of emotional symptoms (P=0.02) and
      emotional symptom bother (P=0.04) than the control group, as well as improved
      spiritual functioning. Family caregivers in the intervention group were more
      likely than control caregivers to endorse items on the Meaning of Life Scale
      (P=0.02). Only improvement in intervention patients' emotional symptom bother
      maintained at follow-up after discontinuing RSV contact (P=0.024). CONCLUSION:
      Delivery of the intervention by RSVs had a positive impact on palliative care
      patients' emotional symptoms and burden and caregivers' meaning in life.
      Meaningful prolonged engagement with palliative care patients and caregivers,
      possibly through alternative modes of treatment delivery such as continued RSV
      contact, may be necessary for maintenance of therapeutic effects.

PMID- 24667182
TI  - Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy.
AB  - Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of
      phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver.
      Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER)
      stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in
      mice to explore the therapeutic impact of Pemt on the progression of diabetic
      nephropathy and diabetes, which was induced by the injection of streptozotocin
      (STZ). Although the blood glucose levels were similar in STZ-induced diabetic
      Pemt+/+ and Pemt-/-mice, the glomerular hypertrophy and albuminuria in Pemt-/-
      mice were significantly reduced. Pemt deficiency reduced the intraglomerular
      F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial
      fibrosis and tubular atrophy. The expression of glucose-regulated protein-78
      (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and
      this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells,
      the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased
      the expression of GRP78, which was reduced by transfection of a shRNA lentivirus
      for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was
      significantly reduced in Pemt-/- diabetic mice, and shRNA-Pemt upregulated the
      phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24
      cells. Taken together, these findings indicate that the inhibition of Pemt
      activity ameliorates the ER stress associated with diabetic nephropathy in a
      model of type 1 diabetes and corrects the functions of the three major pathways
      downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis. 

PMID- 24667184
TI  - Detecting free radicals in sunscreens exposed to UVA radiation using
      chemiluminescence.
AB  - One of the current concerns with the application of nanoparticles in sunscreens,
      and in particular nano-TiO2 and ZnO, is their potential to photogenerate free
      radicals and reactive oxygen species (ROS) when they absorb ultraviolet
      wavelengths from sunlight. Free radicals and ROS are known to be associated with
      UV-induced skin damage and oxidative stress, from which sunscreens are expected
      to offer significant protection. Here we describe a simple method, based on
      chemiluminescence emission, for detecting free radicals generated in commercial
      sunscreens alone, and when applied to various substrates, following exposure to
      UVA (320-400nm) radiation. This photo-induced chemiluminescence (PICL) technique
      could be used to optimise sunscreen formulations so as to minimise free radical
      photogeneration during exposure to sunlight. 

PMID- 24667185
TI  - The Academic Health Department: antidote to antipathy.

PMID- 24667186
TI  - The Academic Health Department: the process of maturation.
AB  - The Academic Health Department (AHD) involves an arrangement between a
      governmental health agency and an academic institution, which provides mutual
      benefits in teaching, service, research, and practice. From its initial
      development in the mid-1980s as the public health equivalent of the relationship
      between a teaching hospital and a medical school, the AHD concept has evolved to
      include multiple levels of governmental public health agencies (local, state, and
      federal) as well as multiple academic institutions (public health, medicine, and
      primary care medical residencies). Throughout the decade of the 2000s, multiple
      influences have impacted both the quality and quantity of AHDs, leading to an
      expansion of AHDs through the Council on Linkages' AHD Learning Community. The
      value of the AHD--as described from prior studies as well as the AHD case
      examples in this current special issue--is evident in its impact on the quality
      of educational experiences and workforce development, agency and academic
      accreditation, practice-based research, and the potential to influence health
      reform.

PMID- 24667183
TI  - High-yield novel leech hyaluronidase to expedite the preparation of specific
      hyaluronan oligomers.
AB  - Hyaluronidases (HAases), particularly leech HAases, have attracted intense
      attention due to their broad applications in medical treatments and great
      potential for the enzymatic production of hyaluronan oligosaccharides. However,
      little is known about this third interesting family of HAases. Here, we applied
      the random amplification of cDNA ends polymerase chain reaction (RACE-PCR)
      approach to identify the first leech HAase-encoding gene. By combining protein
      engineering and high-density culture, we achieved high-level production (8.42 *
      10(5) U ml(-1)) in the yeast Pichia pastoris secretory expression system.
      Compared with the commercial bovine testicular HAase, the recombinant leech HAase
      exhibited superior enzymatic properties. Furthermore, analysis of the hydrolytic
      process suggested that this novel enzyme adopts a nonprocessive endolytic mode,
      yielding a narrow-spectrum of specific HA oligosaccharides with different
      incubation times. Large-scale production of this novel leech HAase will not only
      greatly promote medical applications but also facilitate the enzymatic production
      of specific HA oligosaccharides.

PMID- 24667187
TI  - Integrating public health education in a public health practice setting: the
      experience of the School of Public Health, University at Albany and the New York
      State Department of Health.
AB  - The New York State Department of Health (DOH) has a long history of biomedical
      research, public health policy and program development, peer-reviewed
      scholarship, and teaching. Its evolution as an academic health department
      advanced significantly when the University at Albany and DOH formed the School of
      Public Health Sciences in 1985 to further develop these functions while formally
      training the next generation of public health workers. The School, renamed in
      1990 as the School of Public Health (SPH), was initially located within the DOH
      with its staff as the founding faculty. The curriculum was heavily influenced by
      public health practice imperatives. The SPH has evolved to have an independent
      campus and full-time academic faculty, but the DOH remains closely linked. The
      relationship is governed by a memorandum of understanding that commits both
      partners to provide substantial and continuing resources to the SPH. The SPH
      brings value to the DOH's mission to improve the health of the state's citizens
      by providing an academic focus to problems faced in health department practice
      settings. The opportunity to teach and be involved in an academic environment
      increases the DOH's ability to recruit, retain, and improve the skill level of
      its professional and scientific staff and thereby improve its ability to assess
      health problems and to design and evaluate public health programs. The SPH also
      provides training and support to county health departments and nongovernment
      organizations, which further the DOH's mission, through continuing education
      programs and an online MPH degree program. International exchanges including
      those with China, Vietnam, and the Republic of Georgia have enriched the academic
      environment. Challenges include maintaining sufficient full-time faculty members,
      the need for the SPH to take on broader public health issues than those
      applicable to New York, and the shrinkage of the DOH's workforce and departure of
      many senior scientists who served as faculty. 

PMID- 24667188
TI  - The University of Washington's Community-Oriented Public Health Practice program
      and Public Health-Seattle & King County partnership.
AB  - The Community-Oriented Public Health Practice (COPHP) program, a 2-year in
      residence MPH degree program in the University of Washington School of Public
      Health, has partnered with Public Health-Seattle & King County (PHSKC) since 2002
      to create a mutually beneficial set of programs to improve teaching and address
      community-based public health problems in a practice setting. The COPHP program
      uses a problem-based learning approach that puts students in small groups to work
      on public health problems. Both University of Washington-based and PHSKC-based
      faculty facilitate the classroom work. In the first year for students, COPHP, in
      concert with PHSKC, places students in practicum assignments at PHSKC; in the
      second year, students undertake a master's project (capstone) in a community or
      public health agency. The capstone project entails taking on a problem in a
      community-based agency to improve either the health of a population or the
      capacity of the agency to improve population health. Both the practicum and the
      capstone projects emphasize applying classroom learning in actual public health
      practice work for community-based organizations. This partnership brings PHSKC
      and COPHP together in every aspect of teaching. In essence, PHSKC acts as the
      "academic health department" for COPHP. There are detailed agreements and
      contracts that guide all aspects of the partnership. Both the practicum and
      capstone projects require written contracts. The arrangements for getting non
      University of Washington faculty paid for teaching and advising also include
      formal contracts. 

PMID- 24667189
TI  - Evolution of the Academic Health Department through public health academic and
      practice collaborations.
AB  - In 1997, the Office of Public Health Practice was chartered at Northeast Ohio
      Medical University (NEOMED). Through this office, public health practitioners and
      academics have engaged in informal collaborations, formal collaborations, and
      formal agreements. Projects that have helped public health practitioners included
      a sanitarian preparation course, educational opportunities, and shared faculty
      arrangements. The academic programs have benefited through support in
      accreditation activities, teaching and precepting of public health and medical
      students, and advice on community-oriented curriculum. Formal affiliation
      agreements have been developed between the medical school and 5 local health
      departments, and public health practitioners have been given faculty
      appointments. Factors that have resulted in the longevity of Academic Health
      Department relationships through the Office of Public Health Practice include
      individuals dedicated to these relationships, agencies willing to support
      collaborative efforts, mutually beneficial activities, and a culture conducive to
      continued engagement. 

PMID- 24667190
TI  - The journey to becoming an Academic Health Department in northern Kentucky.
AB  - Various forces of change have come together to create an environment that
      encourages public health departments to explore the Academic Health Department
      concept. This article presents the journey of one health department to meld
      public health practice with academia for the betterment of the community's
      health. Lessons learned are presented to demonstrate how the partnerships
      anticipated possible barriers, avoided problems, moved through the implementation
      stage, and positioned the partnerships for future growth. Key factors that have
      contributed to the success of these collaborations are explored, including why
      they hold promise to meet the needs of the various partners and enable the
      community-academic partnership to thrive beyond the current generation of
      decision makers. While this example is based on one health department's efforts,
      the processes and key factors can be applied to others who wish to take the same
      journey. 

PMID- 24667191
TI  - Forming an academic health department: a case example.
AB  - The disconnect between public health practice and its academic base has major
      implications for training and hiring the future public health workforce, for
      practice-based research, and ultimately for improving the public's health. To
      bridge this disconnect, the University of Tennessee Department of Public Health
      and the Knox County Health Department established an academic health department
      in early 2011 through a memorandum of understanding. This action followed a long
      history of informal collaborations, built on mutual trust. The memorandum of
      understanding identified the scope of academic health department activities,
      clarified responsibilities of each organization, and created a shared coordinator
      position. Accomplishments during the first 18 months include improving the
      efficiency and effectiveness of student field placements; establishing
      collaborative learning sessions delivered jointly by University of Tennessee
      Department of Public Health faculty and Knox County Health Department staff; and
      exploring opportunities for practice-based research. The shared coordinator
      position and an active steering committee are considered fundamental to achieving
      sustainable academic-practice linkages. 

PMID- 24667193
TI  - Developing an academic health department in Northeast Tennessee: a sustainable
      approach through student leadership.
AB  - In an effort to bridge the gap between public health practice and academia, the
      Health Resources and Services Administration-funded Tennessee Public Health
      Training Center (LIFEPATH) has supported establishment of an academic health
      department (AHD) involving the East Tennessee State University College of Public
      Health (COPH) and the Sullivan County Regional Health Department (SCRHD). The
      SCRHD identified a need to increase internal capacity to conduct ongoing
      community health assessment and community-centered practice. Similarly, the COPH
      recognized the need to expand evidence-based practice implementation and
      evaluation opportunities for public health students. Personnel from the SCRHD,
      LIFEPATH, and the COPH developed a formal AHD agreement during the summer of 2012
      and launched the program the subsequent fall semester. One aspect of the
      COPH/SCRHD/LIFEPATH model that addresses financial barriers experienced by other
      AHDs is the competitive awarding of the coordinator position to a doctor of
      public health student from the COPH, demonstrating investment in the model by the
      college. The doctor of public health student gains leadership experience through
      project management, coordination of the local health council, and day-to-day
      facilitation of undergraduate and master's student interns. The SCRHD benefits
      from the formal academic background of graduate-level interns dedicated to
      working in the community. This AHD framework offers an opportunity for doctoral
      level students to develop practical leadership skills in a health department
      while enhancing the capacity of the SCRHD and the COPH to serve their community
      and stakeholders. 

PMID- 24667192
TI  - An academic-public health department partnership for education, research,
      practice, and governance.
AB  - Public health departments and medical schools are often disconnected, yet each
      has much to offer the other. There are 4 areas in which the 2 entities can
      partner; in Atlanta, Georgia, the Morehouse School of Medicine (particularly its
      Prevention Research Center or PRC) and the Fulton County Department of Health and
      Wellness have demonstrated partnership in each area. With respect to teaching,
      the 2 have collaborated on clerkships for medical students and rotations for
      preventive medicine residents. In research, Morehouse faculty and health
      department staff have worked together on projects. In service, the 2 entities
      have been able to put into practice interventions developed through their joint
      research efforts. In governance, the health department has a representative on
      the PRC board, while the PRC principal investigator serves on the Fulton County
      Board of Health. Benefits have accrued to both entities and to the communities
      that they serve. 

PMID- 24667194
TI  - Academic health departments as training sites for future public health leaders: a
      partnership model in Wisconsin.
AB  - BACKGROUND: In 2004, 2 Wisconsin academic health departments partnered with the
      School of Medicine and Public Health, University of Wisconsin-Madison to
      strengthen the public health workforce through a service-learning program that
      prepares the next generation of leaders while addressing local public health
      needs. The Wisconsin Population Health Service Fellowship annually provides 4 to
      6 master's or doctorally trained fellows with 2-year service-learning placements
      in health departments and community-based organizations. PROGRAM BENEFITS:
      Placement communities benefit from fellows' contributions to a broad range of
      public health issues, including chronic and communicable disease prevention,
      health equity, community practice, and policy and systems change. Academic health
      departments and the UW School of Medicine and Public Health enjoy additional
      program benefits, along with the advantages that accrue to the fellows
      themselves. For the academic health departments, this includes increased
      organizational capacity, generation of resources for public health, and a
      stronger and more diverse public health workforce. LESSONS LEARNED: The success
      of the partnership depends upon shared decision making and management, written
      agreements to clarify partner expectations, shared financial and in-kind
      contributions, and collaboration on program evaluation and dissemination.
      CONCLUSIONS: By building upon their respective organizational strengths,
      Wisconsin's academic health departments and the UW School of Medicine and Public
      Health have developed a successful model for transforming talented, highly
      motivated young professionals into confident, emerging public health leaders with
      the cutting-edge skills and connections necessary to improve population health
      outcomes and advance health equity.

PMID- 24667195
TI  - State procurement law: facilitating the collaboration between health department
      and school of public health.
AB  - The mark of an "academic health department" includes shared activity by academic
      and practice partners sustained over time. Despite a long history of productive
      interactivity, the Pennsylvania Department of Health and the University of
      Pittsburgh's Graduate School of Public Health often faced administrative hurdles
      in contracting for projects of mutual interest. Seeking to overcome these
      hurdles, the Commonwealth of Pennsylvania and the University of Pittsburgh's
      Graduate School of Public Health negotiated a Master Agreement on the basis of
      statutes designating both as "public procurement units." This provided a template
      for project specifications, standard financial terms, and a contracting process.
      Since taking effect, the Master Agreement has supported projects in policy
      development, capacity building, workforce development, program evaluation, data
      analysis, and program planning. This experience suggests an approach potentially
      useful for other states and localities seeking to solidify academic health
      department partnerships either envisioned for the future or already in place. 

PMID- 24667196
TI  - Institutionalizing the academic health department within the context of the 3
      fold academic mission.
AB  - A mature model of an academic health department (AHD) that has been
      institutionalized over 2 decades is described within the context of the 3-fold
      traditional mission of academics (teaching, research, and service/practice). This
      adaptive model for AHDs, based on mutual benefits that can be viewed through the
      lenses of both the academic health center mission and the public health functions
      and services, has important implications for AHD sustainability. Continued
      collaboration in any academic-public health partnership will depend in part on
      the commitments of the changing leadership. However, institutionalizing support
      for the academic mission enables this collaboration to transcend changing
      leadership styles and priorities. The collaboration of Duval County Health
      Department and University of Florida College of Medicine-Jacksonville is an
      example of a model of AHD that has endured major changes in leadership within
      both the academic center and the Duval County Health Department. 

PMID- 24667197
TI  - Academic-health department collaborative relationships are reciprocal and
      strengthen public health practice: results from a study of academic research
      centers.
AB  - BACKGROUND: Collaborations between academic institutions and state and local
      health departments have been shown to enhance the public health core functions of
      Assurance by improving the public health workforce's knowledge and skills. Few
      studies have analyzed how academic-health department collaborations enhance
      Assessment and Policy Development core functions. This qualitative study explores
      types of collaborations between health departments and Prevention Research
      Centers (PRCs) and how they align with the core functions. Prevention Research
      Centers are academic institutions funded by the Centers for Disease Control and
      Prevention to conduct public health research and translate research results for
      policies and practices. METHODS: We reviewed each PRC's annual report from fiscal
      year 2011 and abstracted descriptions of PRC-health department collaborations. We
      identified 14 themes of PRC-health department collaborations and conducted a
      qualitative analysis to describe the dimensions and distribution of themes.
      RESULTS: Of the 37 PRCs, 36 reported 215 collaborations with 19 city, 97 county,
      31 state, and 46 tribal health departments. Themes of research, survey, and
      surveillance aligned with the Assessment core function and evaluation, strategic
      planning, technical assistance, and program implementation supported the Policy
      Development and Assurance core functions. Overall, health departments provided on
      the-ground expertise to inform PRC research, ensuring its applicability to public
      health practice. Reciprocally, PRCs improved data quality, increased the
      scientific rigor of health department processes and programs, and filled
      knowledge gaps within health departments. Both PRCs and health departments
      enhanced the relevance of public health programs and practices by grounding
      implementation and evaluation in community needs and views. CONCLUSION: Findings
      from this study demonstrate that PRC-health department collaborations often
      enhanced multiple core functions that could lead to implementation of evidence
      based interventions and continuous quality improvement of public health
      administration at the local, state, and tribal levels. This study highlights the
      value and importance of reciprocal academic-health department partnerships.

PMID- 24667198
TI  - Local health department and academic institution linkages for community health
      assessment and improvement processes: a national overview and local case study.
AB  - Community health improvement processes that yield community health assessments
      (CHAs) and community health improvement plans (CHIPs) provide data and a process
      to determine key community priorities and take action and are ideally
      collaborative endeavors. Nationally, increased focus on CHAs and CHIPs highlights
      the role that Academic Health Departments or other local health department (LHD)
      academic linkages can play in completing CHAs and CHIPs. Drawn from the
      experiences of 5 LHD-academic partnerships that participated in a national
      demonstration and a detailed account of the experience of one, this article
      presents how such linkages can support CHA and CHIP work, ways to anticipate and
      overcome challenges, and the tangible benefits that may be realized for both the
      LHD and the academic partner. Community health improvement processes are ripe
      opportunities for LHD-academic linkages and can be fruitful and mutually
      beneficial partnerships to be used in completing CHAs and CHIPs to measurably
      improve the public's health. 

PMID- 24667199
TI  - Leadership and management--guiding principles, best practices, and core
      attributes.

PMID- 24667200
TI  - Local perspectives on the environmental public health tracking program.
AB  - Strong state-local relationships within the Environmental Public Health Tracking
      Program (Tracking Program) can enhance the ability of the Centers for Disease
      Control and Prevention and state and local health departments to collect and
      analyze data that would help determine links between environmental exposure and
      health. Since the National Association of County & City Health Officials is
      particularly interested in how local-state partnerships could benefit the
      Environmental Public Health Tracking Network, this article features strategies to
      engage local health departments. First, state-local facilitated discussions have
      been shown to positively impact the public's health. Second, Martin County
      conducted a program that taught women to avoid overconsumption of high-mercury
      seafood, which was also implemented in other Florida counties. Finally, the
      Cincinnati Health Department initiated a project that promoted data sharing with
      the state, and the results have also been promising. Such efforts indicate that
      state-local partnerships have the potential to support and enrich the Tracking
      Program. 

PMID- 24667201
TI  - Measuring preparedness: the National Health Security Preparedness Index.

PMID- 24667202
TI  - A liaison-based academic health department in Georgia: a partnership for
      improving community health.
AB  - Public health practice in Georgia and the North Central Health District 5.2 in
      particular is facing several challenges. In recent years, public health program
      funding in the state department and district has been cut or eliminated. Many
      public health workers are scheduled to retire in the next few years. Low pay also
      makes it difficult to attract and retain qualified applicants to local health
      departments. This has become increasingly challenging in an environment where
      experienced public health professionals are becoming limited. Furthermore,
      accredited public health programs such as Mercer University are expected to
      provide practical learning experiences for students. Mutual benefits have
      prompted the North Central Health District and the Public Health Program of
      Mercer University to enter into a formal partnership through an affiliation
      agreement to form the academic health department. This article discusses the
      logic model underlying the academic health department and lessons learned from
      its initial implementation. 

PMID- 24667203
TI  - Physician training rotations in a large urban health department.
AB  - Hospitals are the normal setting for physician residency training within the
      United States. When a hospital cannot provide the specific training needed, a
      special rotation for that experience is arranged. Linkages between clinical and
      public health systems are vital to achieving improvements in overall health
      status in the United States. Nevertheless, most physicians in postgraduate
      residency programs receive neither training nor practical experience in the
      practice of public health. For many years, public health rotations have been
      available within the Los Angeles County Department of Public Health (and its
      antecedent organizations). Arrangements that existed with local medical schools
      for residents to rotate with Los Angeles County Department of Health hospitals
      were extended to include a public health rotation. A general model for the
      rotation ensured that each resident received education and training relevant to
      the clinician in practice. Some parts of the model for experience have changed
      over time while others have not. Also, the challenges and opportunities for both
      trainees and preceptors have evolved and varied over time. A logic model
      demonstrates the components and changes with the public health rotation. Changes
      included alterations in recruitment, expectations, evaluation, formal education,
      and concepts related to the experience. Changes in the rotation model occurred in
      the context of other major environmental changes such as new electronic
      technology, changing expectations for residents, and evolving health services and
      public health systems. Each impacted the public health rotation. The evaluation
      method developed included content tests, assessment of competencies by residents
      and preceptors, and satisfaction measures. Results from the evaluation showed
      increases in competency and a high level of satisfaction after a public health
      rotation. The article includes examples of challenges and benefits to a local
      health department in providing a public health rotation for physicians-in
      training and how these challenges were overcome. 

PMID- 24667204
TI  - Building a sustainable Academic Health Department: the South Carolina model.
AB  - Given the limited resources available to public health, it is critical that
      university programs complement the development needs of agencies. Unfortunately,
      academic and practice public health entities have long been challenged in
      building sustainable collaborations that support practice-based research,
      teaching, and service. The academic health department concept offers a promising
      solution. In South Carolina, the partners started their academic health
      department program with a small grant that expanded into a dynamic infrastructure
      that supports innovative professional exchange and development programs. This
      article provides a background and describes the key elements of the South
      Carolina model: joint leadership, a multicomponent memorandum of agreement, and a
      shared professional development mission. The combination of these elements allows
      the partners to leverage resources and deftly respond to challenges and
      opportunities, ultimately fostering the sustainability of the collaboration. 

PMID- 24667205
TI  - Adequacy of nutrient intakes in elite junior basketball players.
AB  - PURPOSE: The aim of this study was to assess the nutrient intakes of elite junior
      basketball players in comparison with nonathletes. METHODS: A previously designed
      food frequency questionnaire was undertaken by 57 male elite junior basketball
      players 15 to 16 years of age and 53 nonathlete peers. RESULTS: Mean estimated
      energy intake was more than 700 kcal higher in basketball players than in the
      nonathletes (p = .002). In both groups estimated energy intake was ~14% from
      protein, 38% from fat, and ~48% from carbohydrates. For the basketball players,
      estimated protein intake was below 1.4 g/kg in 32% of the group and above 1.7 g/
      kg in 51%, while carbohydrate intake was below 6 g/kg in 56%. Percentages of
      participants who apparently failed to meet the estimated average requirement for
      micronutrients were higher in the nonathlete group. The nutrients most likely to
      fail to meet the recommendations for nutrient density were vitamin A (~70%), zinc
      (49% in basketball players and 30% in nonathletes), niacin and calcium (~30% for
      both micronutrients in both groups). CONCLUSION: Within the limitations of the
      survey methodology, elite junior basketball players appear to consume higher
      absolute energy, macronutrient and micronutrient intakes than nonathletes, but
      the contribution of macronutrients to daily energy intake and the nutrient
      density of food choices was similar for both groups. Elite junior basketball
      players might benefit from nutrition education targeting carbohydrate and protein
      intake. Dietary modifications that increase intakes of vitamin A, zinc, calcium
      and niacin in the diets of both groups might also be of value.

PMID- 24667206
TI  - Treatment of cerebral cavernous malformations: a systematic review and meta
      regression analysis.
AB  - OBJECTIVE: The reported effects of treating cerebral cavernous malformations
      (CCMs) by neurosurgical excision or stereotactic radiosurgery are imprecise and
      vary between studies. METHODS: We searched Ovid Medline, EMBASE and The Cochrane
      Library for peer-reviewed publications of cohort studies describing outcomes of
      treating 20 or more patients with CCM with at least 80% completeness of follow
      up. Two reviewers extracted data to quantify the incidence of a composite outcome
      (death, non-fatal intracranial haemorrhage, or new/worse persistent focal
      neurological deficit) after CCM treatment. We explored associations between
      summary measures of study characteristics and outcome using Poisson meta
      regression analyses. RESULTS: We included 63 cohorts, involving 3424 patients.
      The incidence of the composite outcome was 6.6 (95% CI 5.7 to 7.5) per 100 person
      years after neurosurgical excision (median follow-up 3.3 years) and 5.4 (95% CI
      4.5 to 6.4) after stereotactic radiosurgery (median follow-up 4.1 years). After
      neurosurgical excision the incidence of the composite outcome increased with
      every per cent point increase in patients with brainstem CCM (rate ratio (RR)
      1.03, 95% CI 1.01 to 1.05), and decreased with each more recent study midyear (RR
      0.91, 95% CI 0.85 to 0.98) and each per cent point increase in patients
      presenting with haemorrhage (RR 0.98, 95% CI 0.96 to 1.00). We did not find
      significant associations in studies of stereotactic radiosurgery. CONCLUSIONS:
      The reported risks of CCM treatment (and the lower risks of neurosurgical
      excision over time, from recently bled CCMs, and for CCMs outside the brainstem)
      compare favourably with the risks of recurrent haemorrhage from CCM. Long-term
      effects, especially important for stereotactic radiosurgery, are unknown.

PMID- 24667207
TI  - Risk factors for congenital hydrocephalus: a nationwide, register-based, cohort
      study.
AB  - OBJECTIVES: To investigate the associations between isolated congenital
      hydrocephalus (CHC) and maternal characteristics, maternal medical diseases, and
      medicine intake during pregnancy as well as birth characteristics of the child in
      a retrospective, register-based, nationwide cohort study. Furthermore, to
      identify the risk factors unique for isolated CHC as compared to syndromic CHC.
      METHODS: We established a cohort of all children born in Denmark between 1978 and
      2008. Information on CHC and maternal medical diseases were obtained from the
      National Patient Discharge Register, maternal intake of medicine during pregnancy
      from the National Prescription Drug Register, and birth characteristics of the
      child from the Danish National Birth Register. Rate ratios (RR) of isolated and
      syndromic CHC with 95% CI were estimated using log-linear Poisson regression.
      RESULTS: In a cohort of 1928666 live-born children, we observed 1193 cases of
      isolated CHC (0.062/1000) born children. First-borns had an increased risk of
      isolated CHC compared to later-borns (1.32 95% CI 1.17 to 1.49) (0.72/1000 born
      children). First trimester exposure to maternal use of antidepressants was
      associated with a significantly increased risk of isolated CHC compared to
      unexposed children (RR 2.52, 95% CI 1.47 to 4.29) (1.5/1000 born children). Risk
      factors also found for syndromic CHC were: Male gender, multiples and maternal
      diabetes. CONCLUSIONS: The higher risk for isolated CHC in first-born children as
      well as behavioural aspects and comorbidities associated with maternal use of
      antidepressants, should be the targets for future research. Potential biological
      pathways by which antidepressants may cause hydrocephalus remain to be
      elucidated.

PMID- 24667208
TI  - Enhancement of steroid hydroxylation yield from dehydroepiandrosterone by
      cyclodextrin complexation technique.
AB  - The cyclodextrins (CDs) complexation technique was performed for the enhancement
      of hydroxylation yield from dehydroepiandrosterone (DHEA) by Colletotrichum lini
      ST-1. Using DHEA/methyl-beta-cyclodextrin (M-beta-CD) or DHEA/hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) inclusion complexes as substrate (10g/L), the
      hydroxylation yields were increased by 14.98% and 20.54% respectively, and the
      biotransformation course was shortened by 12h. X-ray diffractometry, differential
      scanning calorimetry, and phase solubility analyses showed an inclusion complex
      was formed between CDs and DHEA at a molar ratio of 1:1, which remarkably
      increased the solubility of DHEA, and then improved substrate biotransformation
      efficiency and hydroxylation yield. Meanwhile, results of thermodynamic
      parameters (DeltaG, DeltaH, DeltaS and Ks) analysis revealed the complexation
      process was spontaneous and DHEA/CDs inclusion complex was stable. Scanning
      electron microscopy and transmission electron microscopy showed that the
      enhancement of DHEA hydroxylation yield also depended on the improvement of cell
      permeability through interaction between cytomembrane and CDs. These results
      suggested that the CDs complexation technique was a promising method to enhance
      steroids hydroxylation yield by increasing steroids solubility and decreasing
      membrane resistance of substrate and product during biotransformation process. 

PMID- 24667209
TI  - Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor
      protein NDP52.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription
      factor in the defence against oxidative stress. Here we provide evidence that
      activation of the Nrf2 pathway reduces the levels of phosphorylated tau by
      induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in
      neurons. The expression of NDP52, which we show has three antioxidant response
      elements (AREs) in its promoter region, is strongly induced by Nrf2, and its
      overexpression facilitates clearance of phosphorylated tau in the presence of an
      autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl
      insoluble tau accumulates in the brains concurrent with decreased levels of
      NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical
      samples of Alzheimer disease cases, and the amount of phosphorylated tau in
      sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These
      results suggest that NDP52 plays a key role in autophagy-mediated degradation of
      phosphorylated tau in vivo. 

PMID- 24667210
TI  - Hypofractionated external beam radiotherapy to boost the prostate with >=85
      Gy/equivalent dose for patients with localised disease at high risk of lymph node
      involvement: feasibility, tolerance and outcome.
AB  - AIMS: To evaluate the tolerance and preliminary outcome of prostate cancer
      patients at high risk of lymph node involvement treated with normofractionated
      whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the
      prostate with an intensity-modulated radiotherapy (IMRT) technique. MATERIALS AND
      METHODS: Between 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk
      of lymph node involvement (70 patients with a Roach index >= 15%; 57 with T-stage
      >= 3a; 40 with Gleason score >= 8) underwent WPRT to a median normofractionated
      dose of 50.4 Gy (range 48.0-50.4 Gy) with conformal three-dimensional techniques
      for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered
      to the prostate with IMRT. The total median delivered dose was 74.4 Gy,
      equivalent to 85.2 Gy in 2 Gy/fractions (alpha/beta = 1.5 Gy). All patients
      underwent androgen deprivation for a total median time of 10.8 months. The
      maximum gastrointestinal and genitourinary acute and late toxicity scores were
      recorded according to the Radiation Therapy Oncology Group scoring system.
      RESULTS: All patients completed treatment as planned. Only 1% of patients
      presented with grade 3 genitourinary or gastrointestinal acute toxicity and none
      scored >= grade 4. With a median follow-up of 57 months, the 5 year probability
      of late grade >=2 genitourinary and gastrointestinal toxicity-free survival was
      79.1 +/- 4.8% and 84.1 +/- 4.5%, respectively. The 5 year biochemical disease
      free survival, local relapse-free survival and distant metastasis-free survival
      were 84.5 +/- 4.5%, 96.0 +/- 2.8% and 86.4 +/- 4.4%, respectively. A pre
      radiotherapy prostate-specific antigen <=0.3 ng/ml was associated with a better 5
      year biochemical disease-free survival (P = 0.036) and distant metastasis-free
      survival (P = 0.049). CONCLUSIONS: The use of a hypofractionated IMRT boost after
      WPRT may allow a minimally invasive dose escalation to successfully treat
      patients with non-metastatic prostate cancer at high risk of lymph node
      involvement. Higher prostate-specific antigen values before radiotherapy may
      require alternative adjuvant treatments to further optimise the outcome of this
      high-risk group of patients.

PMID- 24667211
TI  - Patient selection and radiotherapy volume definition - can we improve the weakest
      links in the treatment chain?

PMID- 24667213
TI  - Prenatal diagnosis in a fetus with de-novo 20q11.2q13.1 deletion and review of
      the literature.

PMID- 24667212
TI  - Changes in HbA1c level over a 12-week follow-up in patients with type 2 diabetes
      following a medication change.
AB  - BACKGROUND: Current guidance about the interval needed before retesting HbA1c
      when monitoring for glycaemic control is based on expert opinion rather than well
      powered studies. The aim of our work was to explore how fast HbA1c changes after
      a change in glucose-lowering medication. This has implications for whether
      routine HbA1c testing intervals before 12 weeks could inform diabetes medication
      adjustments. METHODS: This 12-week cohort study recruited patients from 18
      general practices in the United Kingdom with non-insulin treated diabetes who
      were initiating or changing dose of oral glucose-lowering medication. HbA1c was
      measured at baseline and 2, 4, 8 and 12 weeks after recruitment. HbA1c levels at
      earlier time intervals were correlated with 12-week HbA1c. A ROC curve analysis
      was used to identify the 8-week threshold above which medication adjustment may
      be clinically appropriate. RESULTS: Ninety-three patients were recruited to the
      study. Seventy-nine patients with no change in medication and full 12-week follow
      up had the following baseline characteristics: mean +/- standard deviation age of
      61.3 +/- 10.8 years, 34% were female and diabetes duration of 6.0 +/- 4.3 years.
      Mean HbA1c at baseline, 2, 4, 8 and 12 weeks was 8.7 +/- 1.5%, (72.0 +/- 16.8
      mmol/mol) 8.6 +/- 1.6% (70.7 +/- 17.0 mmol/mol), 8.4 +/- 1.5% (68.7 +/- 15.9
      mmol/mol), 8.2 +/- 1.4% (66.3 +/- 15.8 mmol/mol) and 8.1 +/- 1.4% (64.8 +/- 15.7
      mmol/mol) respectively. At the end of the study 61% of patients had sub-optimal
      glycaemic control (HbA1c>7.5% or 59 mmol/mol). The 8-week change correlated
      significantly with the 12-week change in HbA1c and an HbA1c above 8.2% (66
      mmol/mol) at 8 weeks correctly classified all 28 patients who had not achieved
      glycaemic control by 12 weeks. CONCLUSIONS/INTERPRETATION: This is the first
      study designed with sufficient power to examine short-term changes in HbA1c. The
      12-week change in HbA1c can be predicted 8 weeks after a medication change. Many
      participants who had not achieved glycaemic control after 12 weeks may have
      benefitted from an earlier review of their HbA1c and medication.

PMID- 24667214
TI  - Proteomics analysis of the DF-1 chicken fibroblasts infected with avian reovirus
      strain S1133.
AB  - BACKGROUND: Avian reovirus (ARV) is a member of the Orthoreovirus genus in the
      Reoviridae family. It is the etiological agent of several diseases, among which
      viral arthritis and malabsorption syndrome are the most commercially important,
      causing considerable economic losses in the poultry industry. Although a small
      but increasing number of reports have characterized some aspects of ARV
      infection, global changes in protein expression in ARV-infected host cells have
      not been examined. The current study used a proteomics approach to obtain a
      comprehensive view of changes in protein levels in host cells upon infection by
      ARV. METHODOLOGY AND PRINCIPAL FINDINGS: The proteomics profiles of DF-1 chicken
      fibroblast cells infected with ARV strain S1133 were analyzed by two-dimensional
      differential-image gel electrophoresis. The majority of protein expression
      changes (>= 1.5 fold, p<0.05) occurred at 72 h post-infection. Matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry identified 51
      proteins with differential expression levels, including 25 that were upregulated
      during ARV infection and 26 that were downregulated. These proteins were divided
      into eight groups according to biological function: signal transduction, stress
      response, RNA processing, the ubiquitin-proteasome pathway, lipid metabolism,
      carbohydrate metabolism, energy metabolism, and cytoskeleton organization. They
      were further examined by immunoblotting to validate the observed alterations in
      protein expression. CONCLUSION/SIGNIFICANCE: This is the first report of a time
      course proteomic analysis of ARV-infected host cells. Notably, all identified
      proteins involved in signal transduction, RNA processing, and the ubiquitin
      proteasome pathway were downregulated in infected cells, whereas proteins
      involved in DNA synthesis, apoptosis, and energy production pathways were
      upregulated. In addition, other differentially expressed proteins were linked
      with the cytoskeleton, metabolism, redox regulation, and stress response. These
      proteomics data provide valuable information about host cell responses to ARV
      infection and will facilitate further studies of the molecular mechanisms
      underlying ARV pathogenesis.

PMID- 24667216
TI  - Prevalent RNA recognition motif duplication in the human genome.
AB  - The sequence-specific recognition of RNA by proteins is mediated through various
      RNA binding domains, with the RNA recognition motif (RRM) being the most frequent
      and present in >50% of RNA-binding proteins (RBPs). Many RBPs contain multiple
      RRMs, and it is unclear how each RRM contributes to the binding specificity of
      the entire protein. We found that RRMs within the same RBP (i.e., sibling RRMs)
      tend to have significantly higher similarity than expected by chance. Sibling RRM
      pairs from RBPs shared by multiple species tend to have lower similarity than
      those found only in a single species, suggesting that multiple RRMs within the
      same protein might arise from domain duplication followed by divergence through
      random mutations. This finding is exemplified by a recent RRM domain duplication
      in DAZ proteins and an ancient duplication in PABP proteins. Additionally, we
      found that different similarities between sibling RRMs are associated with
      distinct functions of an RBP and that the RBPs tend to contain repetitive
      sequences with low complexity. Taken together, this study suggests that the
      number of RBPs with multiple RRMs has expanded in mammals and that the multiple
      sibling RRMs may recognize similar target motifs in a cooperative manner. 

PMID- 24667217
TI  - Spinal subdural abscess: a rare complication of decubitus ulcer.
AB  - Spinal subdural abscess (SSA) is an uncommon entity. The exact incidence is
      unknown, with very few cases reported in the literature. This condition may
      result in spinal cord compression, thus constituting a medical and neurosurgical
      emergency. The pathogenesis of SSA is not well-described, and the available
      knowledge is based on case observations only. There is only one case report that
      describes direct seeding from decubitus ulcers as a possible mechanism for
      development of SSA. We report a case of subacute onset of quadriplegia in a male
      patient, age 55 years, due to spinal cord compression from SSA and superimposed
      spinal subdural hematoma. The direct seeding from decubitus ulcers is thought to
      be the cause of infection in our patient. We present this case of SSA to
      elucidate and review the predisposing factors, pathogenesis, clinical
      presentation, diagnostic modalities, and treatment regarding management of this
      rare disorder. 

PMID- 24667215
TI  - RF3:GTP promotes rapid dissociation of the class 1 termination factor.
AB  - Translation termination is promoted by class 1 and class 2 release factors in all
      domains of life. While the role of the bacterial class 1 factors, RF1 and RF2, in
      translation termination is well understood, the precise contribution of the
      bacterial class 2 release factor, RF3, to this process remains less clear. Here,
      we use a combination of binding assays and pre-steady state kinetics to provide a
      kinetic and thermodynamic framework for understanding the role of the
      translational GTPase RF3 in bacterial translation termination. First, we find
      that GDP and GTP have similar affinities for RF3 and that, on average, the t1/2
      for nucleotide dissociation from the protein is 1-2 min. We further show that
      RF3:GDPNP, but not RF3:GDP, tightly associates with the ribosome pre- and post
      termination complexes. Finally, we use stopped-flow fluorescence to demonstrate
      that RF3:GTP enhances RF1 dissociation rates by over 500-fold, providing the
      first direct observation of this step. Importantly, catalytically inactive
      variants of RF1 are not rapidly dissociated from the ribosome by RF3:GTP, arguing
      that a rotated state of the ribosome must be sampled for this step to efficiently
      occur. Together, these data define a more precise role for RF3 in translation
      termination and provide insights into the function of this family of
      translational GTPases. 

PMID- 24667218
TI  - Finding the key to a better code: code team restructure to improve performance
      and outcomes.
AB  - Code teams respond to acute life threatening changes in a patient's status 24
      hours a day, 7 days a week. If any variable, whether a medical skill or non
      medical quality, is lacking, the effectiveness of a code team's resuscitation
      could be hindered. To improve the overall performance of our hospital's code
      team, we implemented an evidence-based quality improvement restructuring plan.
      The code team restructure, which occurred over a 3-month period, included a
      defined number of code team participants, clear identification of team members
      and their primary responsibilities and position relative to the patient, and
      initiation of team training events and surprise mock codes (simulations). Team
      member assessments of the restructured code team and its performance were
      collected through self-administered electronic questionnaires. Time-to
      defibrillation, defined as the time the code was called until the start of
      defibrillation, was measured for each code using actual time recordings from code
      summary sheets. Significant improvements in team member confidence in the skills
      specific to their role and clarity in their role's position were identified.
      Smaller improvements were seen in team leadership and reduction in the amount of
      extra talking and noise during a code. The average time-to-defibrillation during
      real codes decreased each year since the code team restructure. This type of code
      team restructure resulted in improvements in several areas that impact the
      functioning of the team, as well as decreased the average time-to-defibrillation,
      making it beneficial to many, including the team members, medical institution,
      and patients. 

PMID- 24667219
TI  - Cannabinoid hyperemesis syndrome: a case report and review of pathophysiology.
AB  - Cannabis is the most widely used illicit drug in the United States, with lifetime
      prevalence of use estimated at 42% to 46%. The antiemetic properties of cannabis
      are well-known by the medical community and the general public; however, less
      well-recognized is the paradoxical potential for certain chronic users to develop
      hyperemesis. We describe in this case a patient with prior extensive work-up for
      nausea and vomiting and previous diagnosis of cyclic vomiting syndrome who
      presented with characteristic features of cannabinoid hyperemesis syndrome. We
      review the current literature for this condition and highlight potential
      mechanisms for its pathogenesis. 

PMID- 24667220
TI  - Variability of door-to-device times at a rural tertiary care center.
AB  - OBJECTIVES: Target door-to-device (DTD) time for ST-elevation myocardial
      infarction (STEMI) patients has been 90 minutes, with no distinction between
      urban and rural hospitals. Rural hospitals have longer DTD times for transferred
      patients attributed to long transportation times from referring hospitals. Longer
      DTD times have also been reported during after-hours. The aim of the study was to
      determine whether DTD times at our rural facility were impacted by arrival
      method, arrival time period, and season. DESIGN: Retrospective chart review.
      SETTING: Rural tertiary care center in central Wisconsin. METHODS: We studied 412
      patients presenting with STEMI after initiation of the Rescue One program for
      rapid triage and transfer from October 2006 through December 2012. They were
      subdivided by arrival method, arrival time (ON=Monday-Friday, 8 AM-5 PM;
      OFF=after-hours, weekends, holidays), and season. Median DTD times and
      proportions below and above 90 minutes were compared. RESULTS: Median DTD time
      for all groups, which include both directly admitted and transferred patients,
      was 85 minutes with 60% of patients achieving DTD times below 90 minutes while 30
      day mortality was 5.3%. Median DTD time was 67 minutes for the Emergency
      Department (ED) (n=164), 95 minutes for Transfers (n=204), 68 minutes for Urgent
      Care (n=22) and 86 minutes for Field (n=22). ED had the highest proportion of
      patients achieving goal DTD time (81%) compared to Transfers (42%). Patients
      arriving by ED during OFF hours had a median DTD time 28 minutes longer than
      during ON hours with 21% fewer patients achieving goal DTD time, attributed to
      the time required to call in the catheterization team. Seasonal variability was
      observed due to differences in pre-hospital ambulance transportation times in the
      Field group. CONCLUSIONS: Our data confirm that in a rural facility such as ours,
      ED patients arriving during after-hours and transferred patients have longer DTD
      times. Methods are being implemented to shorten the time to assemble the
      catheterization lab team during after-hours. Better performance will be seen once
      the first medical contact to device (FTD) time goal of 120 minutes for
      transferred patients is adopted at our institution. Fibrinolytic therapy should
      be considered at referring institutions where the FTD time is expected to exceed
      120 minutes.

PMID- 24667221
TI  - Intramuscular abdominal wall endometriosis treated by ultrasound-guided ethanol
      injection.
AB  - Abdominal wall endometriosis (AWE) is a rare condition that usually develops in a
      surgical scar resulting from a Caesarean section. While commonly seen in the
      cutaneous and subcutaneous fat tissue at the Caesarean scar level, its
      intramuscular localization is quite rare. Its treatment options consist of the
      excision of the lesion and/or hormonal therapies, although wide surgical excision
      is the treatment of choice in the literature. Wide surgical excision may create a
      defect in the abdominal wall and may increase the risk of hernia formation and
      mesh complications. This case report describes the clinical and radiological
      findings and treatment modalities of endometriosis that have appeared in the
      rectus abdominis muscle of a 25-year-old patient at the Caesarean scar level.
      Sclerotherapy may be used for endometrioma. We present a new and alternative
      treatment method using ultrasound-guided intralesional ethanol injection for AWE.
      Compared with the complications of surgical excision, the complications of
      sclerotherapy by ethanol are at a more acceptable level. Sclerotherapy by ethanol
      injection may be an alternative treatment to surgery for AWE. 

PMID- 24667222
TI  - Synchronous distal pancreatic metastatic lesion arising from colonic
      adenocarcinoma: case report and literature review.
AB  - Solitary metastatic pancreatic lesions comprise 0.5% to 3% of all pancreas
      neoplasms, most commonly arising from primary tumors of the kidney, lung, or
      colon. Synchronous metastatic pancreatic lesions are exceptionally rare. Only 25
      cases of isolated colorectal pancreatic metastasis amenable to resection have
      been reported, 11 of those in the distal pancreas. To our knowledge we report the
      first case of a primary colonic malignancy with a synchronous distal pancreatic
      metastatic lesion treated with resection. 

PMID- 24667223
TI  - Blessing for the bleeder: bevacizumab in hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized
      by uncontrolled multisystem angiogenesis with epistaxis, gastrointestinal
      bleeding, iron-deficiency anemia, and arteriovenous malformations, and is often
      associated with increased levels of vascular endothelial growth factor (VEGF).
      Bevacizumab, a VEGF inhibitor, reduces epistaxis, telangiectasias, and iron
      deficiency anemia. We present the case of a woman with HHT and chronic
      gastrointestinal bleeding who required iron supplementation and multiple blood
      transfusions. Bevacizumab resulted in marked symptom improvement and transfusion
      independence. Our report describes the dose schedule and calls for a randomized,
      controlled trial demonstrating the value of bevacizumab therapy.

PMID- 24667224
TI  - Streptococcus pyogenes sternoclavicular septic arthritis in a healthy adult.
AB  - Sternoclavicular septic arthritis is a rare infection, accounting for
      approximately 1% of septic arthritis in the general population. Staphylococcus
      aureus is the predominant etiologic agent, and it usually occurs in relatively
      young adults with some type of predisposition to infection. We report, to the
      best of our knowledge, the first case of group A streptococcal, sternoclavicular
      arthritis in a previously healthy 62-year-old male patient. We present a detailed
      history and physical examination, with laboratory findings, imaging studies,
      cultures, and therapy. 

PMID- 24667225
TI  - Joint British Societies' consensus recommendations for the prevention of
      cardiovascular disease (JBS3).

PMID- 24667226
TI  - Expression and potential roles of HLA-G in human spermatogenesis and early
      embryonic development.
AB  - As one of the non-classical major histocompatibility complex(MHC)-1 antigens,
      Human Leukocyte Antigen G (HLA-G), has been suggested as a prognostic marker to
      identify the embryo developmental potential. In the present study, we
      investigated the potential roles of HLA-G in human spermatogenesis and early
      embryonic development. Quantitative real-time PCR analysis revealed that HLA-G's
      expression was increased with increased Johnsen score in testicular tissues.
      There was no significant difference in HLA-G mRNA expression between testicular
      tissues with Johnsen score of 8-9 and normal sperm from ejaculated semen. HLA-G
      mRNA expression was detected in human zygotes, embryos and blastocysts but not in
      unfertilized oocytes. In testicular tissues where sperm was obtained by
      testicular sperm extraction (Johnsen score was 8 to 9), there were no
      correlations between HLA-G mRNA expression and fertilization, cleavage and high
      quality embryo rates. At 48-72 h post-fertilization, HLA-G expression was higher
      in fast growing embryos. HLA-G specific siRNA injection into zygotes not only
      slowed down embryonic cleavage rate at 48 h post-fertilization, but also down
      regulated the expression of embryo metabolism related gene (SLC2A1) and cell
      cycle-regulated gene (CCND2). Taken together, our findings suggested that HLA-G
      plays significant roles in human spermatogenesis and early embryonic development.

PMID- 24667227
TI  - Model-based analysis of thromboxane B2 and prostaglandin E2 as biomarkers in the
      safety evaluation of naproxen.
AB  - The assessment of safety in traditional toxicology protocols relies on evidence
      arising from observed adverse events (AEs) in animals and on establishing their
      correlation with different measures of drug exposure (e.g., Cmax and AUC). Such
      correlations, however, ignore the role of biomarkers, which can provide further
      insight into the underlying pharmacological mechanisms. Here we use naproxen as a
      paradigm drug to explore the feasibility of a biomarker-guided approach for the
      prediction of AEs in humans. A standard toxicology protocol was set up for the
      evaluation of effects of naproxen in rat, in which four doses were tested (7.5,
      15, 40 and 80 mg/kg). In addition to sparse blood sampling for the assessment of
      exposure, thromboxane B2 and prostaglandin E2 were also collected in satellite
      groups. Nonlinear mixed effects modelling was used to evaluate the predictive
      performance of the approach. A one-compartmental model with first order
      absorption was found to best describe the pharmacokinetics of naproxen. A
      nonlinear relationship between dose and bioavailability was observed which leads
      to a less than proportional increase in naproxen concentrations with increasing
      doses. The pharmacodynamics of TXB2 and PGE2 was described by direct inhibition
      models with maximum pharmacological effects achieved at doses >7.5 mg/kg. The
      predicted PKPD relationship in humans was within 10-fold of the values previously
      published. Moreover, our results indicate that biomarkers can be used to assess
      interspecies differences in PKPD and extrapolated data from animals to humans.
      Biomarker sampling should be used systematically in general toxicity studies.

PMID- 24667228
TI  - Thinking beyond the silos: emerging priorities in workforce development for state
      and local government public health agencies.
AB  - CONTEXT: Discipline-specific workforce development initiatives have been a focus
      in recent years. This is due, in part, to competency-based training standards and
      funding sources that reinforce programmatic silos within state and local health
      departments. OBJECTIVE: National leadership groups representing the specific
      disciplines within public health were asked to look beyond their discipline
      specific priorities and collectively assess the priorities, needs, and
      characteristics of the governmental public health workforce. DESIGN: The
      challenges and opportunities facing the public health workforce and crosscutting
      priority training needs of the public health workforce as a whole were evaluated.
      Key informant interviews were conducted with 31 representatives from public
      health member organizations and federal agencies. Interviews were coded and
      analyzed for major themes. Next, 10 content briefs were created on the basis of
      priority areas within workforce development. Finally, an in-person priority
      setting meeting was held to identify top workforce development needs and
      priorities across all disciplines within public health. PARTICIPANTS:
      Representatives from 31 of 37 invited public health organizations participated,
      including representatives from discipline-specific member organizations, from
      national organizations and from federal agencies. RESULTS: Systems thinking,
      communicating persuasively, change management, information and analytics, problem
      solving, and working with diverse populations were the major crosscutting areas
      prioritized. CONCLUSIONS: Decades of categorical funding created a highly
      specialized and knowledgeable workforce that lacks many of the foundational
      skills now most in demand. The balance between core and specialty training should
      be reconsidered.

PMID- 24667229
TI  - Does nonprofit hospital community benefit vary by state?
AB  - The initial analysis of the revised Internal Revenue Service Schedule H community
      benefit report revealed that only about 5% of these dollars are allocated for
      community health improvement activities. These results have prompted suggestions
      for improved community health via community benefit reform, given the poor
      performance of the US population health system. However, if such a reform were
      enacted, it would have differential impacts across states due to variation in
      nonprofit hospitals, expenditures, and community benefit allocations. We model
      this variation, indicating that the range in per capita benefit across states
      would approximately range from $30 to $335. This variation should be taken into
      account as community benefit reform is considered.

PMID- 24667230
TI  - Bifurcation of the endocytic pathway into Rab5-dependent and -independent
      transport to the vacuole.
AB  - The yeast Rab5 homologue, Vps21p, is known to be involved both in the vacuolar
      protein sorting (VPS) pathway from the trans-Golgi network to the vacuole, and in
      the endocytic pathway from the plasma membrane to the vacuole. However, the
      intracellular location at which these two pathways converge remains unclear. In
      addition, the endocytic pathway is not completely blocked in yeast cells lacking
      all Rab5 genes, suggesting the existence of an unidentified route that bypasses
      the Rab5-dependent endocytic pathway. Here we show that convergence of the
      endocytic and VPS pathways occurs upstream of the requirement for Vps21p in these
      pathways. We also identify a previously unidentified endocytic pathway mediated
      by the AP-3 complex. Importantly, the AP-3-mediated pathway appears mostly intact
      in Rab5-disrupted cells, and thus works as an alternative route to the
      vacuole/lysosome. We propose that the endocytic traffic branches into two routes
      to reach the vacuole: a Rab5-dependent VPS pathway and a Rab5-independent AP-3
      mediated pathway. 

PMID- 24667231
TI  - Water intake accelerates parasympathetic reactivation after high-intensity
      exercise.
AB  - It has been shown that water intake (WI) improves postexercise parasympathetic
      recovery after moderate-intensity exercise session. However, the potential
      cardiovascular benefit promoted by WI has not been investigated after high
      intensity exercise. PURPOSE: To assess the effects of WI on post high-intensity
      parasympathetic recovery. METHODS: Twelve recreationally active young men
      participated in the study (22 +/- 1.4 years, 24.1 +/- 1.6 kg.m(-2)). The
      experimental protocol consisted of two visits to the laboratory. Each visit
      consisted in the completion of a 30-min high-intensity [~80% of maximal heart
      rate (HR)] cycle ergometer aerobic session performing randomly the WI or control
      (CON, no water consumption) intervention at the end of the exercise. HR and RR
      intervals (RRi) were continuously recorded by a heart rate monitor before, during
      and after the exercise. Differences in HR recovery [e.g., absolute heart rate
      decrement after 1 min of recovery (HRR60s) and time-constant of the first order
      exponential fitting curve of the HRR (HRRtau)] and in postexercise vagal-related
      heart rate variability (HRV) indexes (rMSSD30s, rMSSD, pNN50, SD1 and HF) were
      calculated and compared for WI and CON. RESULTS: A similar HR recovery and an
      increased postexercise HRV [SD1 = 9.4 +/- 5.9 vs. 6.0 +/- 3.9 millisecond, HF(ln)
      = 3.6 +/- 1.4 vs. 2.4 +/- 1.3 millisecond(2), for WI and CON, respectively; p <
      .05] was observed in WI compared with CON. CONCLUSION: The results suggest that
      WI accelerates the postexercise parasympathetic reactivation after high-intensity
      exercise. Such outcome reveals an important cardioprotective effect of WI.

PMID- 24667232
TI  - Tissue-, sex- and development-specific transcription profiles of eight UDP
      glucuronosyltransferase genes in zebrafish (Danio rerio) and their regulation by
      activator of aryl hydrocarbon receptor.
AB  - UDP-Glucuronosyltransferases (Ugts) are phase II biotransformation enzymes that
      glucuronidate numerous endogenous and xenobiotic substrates. Based on the
      reported zebrafish Ugt gene repertoire, primers for the Ugt1a and Ugt1b family
      and for individual Ugt5a1, Ugt5a3, Ugt5a4, Ugt5a5, Ugt5c2 and Ugt5c3 were
      designed and applied in RT-qPCR analyses. Transcriptional expression profiles of
      these Ugts were analyzed in intestine, liver, gonad and brain of female and male
      adult zebrafish and at different embryonic developmental stages. We found tissue
      , sex- and developmental-specific expression patterns for all isoforms.
      Throughout all tissues, the most abundant Ugts were Ugt1a, Ugt1b, Ugt5a1 and
      Ugt5a3. Expression during embryonic development was assessed between 24 and 120
      hpf. Ugts showed a development-dependent expression. The pattern of Ugt1a, Ugt1b,
      Ugt5a1, Ugt5a3 and Ugt5a4 were similar with highest expression at 24 hpf followed
      by a decrease and rebound increase up to 120 hpf. To analyze for transcriptional
      regulation of Ugts by the arylhydrocarbon receptor (ahr2), zebrafish eleuthero
      embryos were exposed to 5, 25 and 50MUg/L benzo(a)pyrene (BaP), a model ahr2
      regulator for cyp1a. Besides transcriptional induction of ahr2 and cyp1a, BaP
      produced a significant induction of Ugt1a, Ugt5a1, Ugt5a3 and Ugt5a5 as well as a
      down-regulation of Ugt1b. These data demonstrate the link between ahr2 signalling
      and transcriptional expression of Ugt genes. This is the first study showing
      transcriptional expression of eight different Ugts in tissues and during
      embryonic development and offers new perspectives on the involvement of Ugts in
      fish xenobiotic metabolism.

PMID- 24667233
TI  - Metabolomic, behavioral, and reproductive effects of the synthetic estrogen 17
      alpha-ethinylestradiol on the unionid mussel Lampsilis fasciola.
AB  - The endocrine disrupting effects of estrogenic compounds in surface waters on
      fish, such as feminization of males and altered sex ratios, may also occur in
      aquatic invertebrates. However, the underlying mechanisms of action and toxicity,
      especially in native freshwater mussels (Order Unionoida), remain undefined. This
      study evaluated the effects of a 12-day exposure of 17 alpha-ethinylestradiol
      (EE2), a synthetic estrogen in oral contraceptives commonly found in surface
      waters, on the behavior, condition, metabolism, and reproductive status of
      Lampsilis fasciola. Adult mussels of both sexes were exposed to a control and two
      concentrations of EE2 (0 ng/L, 5 ng/L considered to be environmentally relevant,
      and 1,000 ng/L designed to provide a positive metabolic response), and samples of
      gill tissue were taken on days 4 and 12; gills were used because of the variety
      of critical processes they mediate, such as feeding, ion exchange, and siphoning.
      Observations of mussel behavior (mantle display, siphoning, and foot movement)
      were made daily, and condition of conglutinates (packets of eggs and/or
      glochidia) released by females was examined. No significant effects of EE2 on
      glochidia mortality, conglutinate condition, female marsupial gill condition, or
      mussel foot extension were observed. However, exposure to both concentrations of
      EE2 significantly reduced male siphoning and mantle display behavior of females.
      Metabolomics analyses identified 207 known biochemicals in mussel gill tissue and
      showed that environmentally relevant EE2 concentrations led to decreases in
      glycogen metabolism end products, glucose, and several essential fatty acids in
      females after 12 days, indicating reductions in energy reserves that could
      otherwise be used for growth or reproduction. Moreover, males and females showed
      significant alterations in metabolites involved in signal transduction, immune
      response, and neuromodulation. Most of these changes were apparent at 1,000 ng/L
      EE2, but similar metabolites and pathways were also affected at 5 ng/L EE2.
      Components of the extracellular matrix of gill tissue were also altered. These
      results demonstrate the utility of metabolomics when used in conjunction with
      traditional physiological and behavioral toxicity test endpoints and establish
      the usefulness of this approach in determining possible underlying toxicological
      mechanisms of EE2 in exposed freshwater mussels.

PMID- 24667234
TI  - Identification of the Nrf2-Keap1 pathway in the European eel Anguilla anguilla:
      role for a transcriptional regulation of antioxidant genes in aquatic organisms.
AB  - Antioxidant defences play a central role in cell protection against a wide
      variety of environmental stressors, their variations being thus frequently
      studied to reveal oxidative stress conditions in fish. The Nrf2-Keap1 pathway is
      among the main mechanisms of transcriptional regulation in mammalians, but its
      involvement in modulation of antioxidant system of aquatic organisms is still
      largely unexplored. The present study focused on the identification of Nrf2 and
      Keap1 in the European eel Anguilla anguilla using liver slices as an in vitro
      model during an oxidative challenge. The mRNA levels of Nrf2, Keap1 and typical
      Nrf2 target genes (catalase, glutathione peroxidase 1 and glutathione S
      transferase pi) were analyzed at different H2O2 exposure times to investigate the
      time course activation of these molecular responses. Obtained results showed a
      coordinated transcriptional regulation of CAT, GPx1 and GSTpi, also suggesting
      that Nrf2 de novo synthesis is required for the protracted induction of such
      antioxidant genes. Further, Keap1 variations would support its role in switching
      off these molecular responses, providing novel insight on the importance of the
      Nrf2-Keap1 pathway in the regulation of antioxidant genes in marine species.

PMID- 24667235
TI  - Early life perfluorooctanesulphonic acid (PFOS) exposure impairs zebrafish
      organogenesis.
AB  - As a persistent organic contaminant, perfluorooctanesulphonic acid (PFOS) has
      been widely detected in the environment, wildlife, and humans. The present study
      revealed that zebrafish embryos exposed to 16 MUM PFOS during a sensitive window
      of 48-96 hour post-fertilization (hpf) disrupted larval morphology at 120 hpf.
      Malformed zebrafish larvae were characterized by uninflated swim bladder, less
      developed gut, and curved spine. Histological and ultrastructural examination of
      PFOS-exposed larvae showed structural alterations in swim bladder and gut. Whole
      genome microarray was used to identify the early transcripts dysregulated
      following exposure to 16 MUM PFOS at 96 hpf. In total, 1278 transcripts were
      significantly misexpressed (p<0.05) and 211 genes were changed at least two-fold
      upon PFOS exposure in comparison to the vehicle-exposed control group. A PFOS
      induced network of perturbed transcripts relating to swim bladder and gut
      development revealed that misexpression of genes were involved in organogenesis.
      Taken together, early life stage exposure to PFOS perturbs various molecular
      pathways potentially resulting in observed defects in swim bladder and gut
      development.

PMID- 24667236
TI  - Comprehensive analysis of single- and multi-vehicle large truck at-fault crashes
      on rural and urban roadways in Alabama.
AB  - The research described in this paper analyzed injury severities at a disaggregate
      level for single-vehicle (SV) and multi-vehicle (MV) large truck at-fault
      accidents for rural and urban locations in Alabama. Given the occurrence of a
      crash, four separate random parameter logit models of injury severity (with
      possible outcomes of major, minor, and possible or no injury) were estimated. The
      models identified different sets of factors that can lead to effective policy
      decisions aimed at reducing large truck-at-fault accidents for respective
      locations. The results of the study clearly indicated that there are differences
      between the influences of a variety of variables on the injury severities
      resulting from urban vs. rural SV and MV large truck at-fault accidents. The
      results showed that some variables were significant only in one type of accident
      model (SV or MV) but not in the other accident model. Again, some variables were
      found to be significant in one location (rural or urban) but not in other
      locations. The study also identified important factors that significantly impact
      the injury severity resulting from SV and MV large truck at-fault accidents in
      urban and rural locations based on the estimated values of average direct pseudo
      elasticity. A careful study of the results of this study will help policy makers
      and transportation agencies identify location specific recommendations to
      increase safety awareness related to large truck involved accidents and to
      improve overall highway safety. 

PMID- 24667239
TI  - Making a hash of data: what risks to privacy does the NHS's care.data scheme
      pose?

PMID- 24667237
TI  - Characterization of chikungunya virus induced host response in a mouse model of
      viral myositis.
AB  - While a number of studies have documented the persistent presence of chikungunya
      virus (CHIKV) in muscle tissue with primary fibroblast as the preferable cell
      target, little is known regarding the alterations that take place in muscle
      tissue in response to CHIKV infection. Hence, in the present study a permissive
      mouse model of CHIKV infection was established and characterized in order to
      understand the pathophysiology of the disease. The two dimensional
      electrophoresis of muscle proteome performed for differential analysis indicated
      a drastic reprogramming of the proteins from various classes like stress,
      inflammation, cytoskeletal, energy and lipid metabolism. The roles of the
      affected proteins were explained in relation to virus induced myopathy which was
      further supported by the histopathological and behavioural experiments proving
      the lack of hind limb coordination and other loco-motor abnormalities in the
      infected mice. Also, the level of various pro-inflammatory mediators like IL-6,
      MCP-1, Rantes and TNF-alpha was significantly elevated in muscles of infected
      mice. Altogether this comprehensive study of characterizing CHIKV induced mouse
      myopathy provides many potential targets for further evaluation and biomarker
      study. 

PMID- 24667238
TI  - Menage a trois: post-transcriptional control of the key enzyme for cell envelope
      synthesis by a base-pairing small RNA, an RNase adaptor protein, and a small RNA
      mimic.
AB  - In Escherichia coli, small RNAs GlmY and GlmZ feedback control synthesis of
      glucosamine-6-phosphate (GlcN6P) synthase GlmS, a key enzyme required for
      synthesis of the cell envelope. Both small RNAs are highly similar, but only GlmZ
      is able to activate the glmS mRNA by base-pairing. Abundance of GlmZ is
      controlled at the level of decay by RNase adaptor protein RapZ. RapZ binds and
      targets GlmZ to degradation by RNase E via protein-protein interaction. GlmY
      activates glmS indirectly by protecting GlmZ from degradation. Upon GlcN6P
      depletion, GlmY accumulates and sequesters RapZ in an RNA mimicry mechanism, thus
      acting as an anti-adaptor. As a result, this regulatory circuit adjusts synthesis
      of GlmS to the level of its enzymatic product, thereby mediating GlcN6P
      homeostasis. The interplay of RNase adaptor proteins and anti-adaptors provides
      an elegant means how globally acting RNases can be re-programmed to cleave a
      specific transcript in response to a cognate stimulus. 

PMID- 24667241
TI  - Highly dynamic animal contact network and implications on disease transmission.
AB  - Contact patterns among hosts are considered as one of the most critical factors
      contributing to unequal pathogen transmission. Consequently, networks have been
      widely applied in infectious disease modeling. However most studies assume static
      network structure due to lack of accurate observation and appropriate analytic
      tools. In this study we used high temporal and spatial resolution animal position
      data to construct a high-resolution contact network relevant to infectious
      disease transmission. The animal contact network aggregated at hourly level was
      highly variable and dynamic within and between days, for both network structure
      (network degree distribution) and individual rank of degree distribution in the
      network (degree order). We integrated network degree distribution and degree
      order heterogeneities with a commonly used contact-based, directly transmitted
      disease model to quantify the effect of these two sources of heterogeneity on the
      infectious disease dynamics. Four conditions were simulated based on the
      combination of these two heterogeneities. Simulation results indicated that
      disease dynamics and individual contribution to new infections varied
      substantially among these four conditions under both parameter settings. Changes
      in the contact network had a greater effect on disease dynamics for pathogens
      with smaller basic reproduction number (i.e. R0 < 2). 

PMID- 24667240
TI  - A high throughput screening assay system for the identification of small molecule
      inhibitors of gsp.
AB  - Mis-sense mutations in the alpha-subunit of the G-protein, Gsalpha, cause fibrous
      dysplasia of bone/McCune-Albright syndrome. The biochemical outcome of these
      mutations is constitutively active Gsalpha and increased levels of cAMP. The aim
      of this study was to develop an assay system that would allow the identification
      of small molecule inhibitors specific for the mutant Gsalpha protein, the so
      called gsp oncogene. Commercially available Chinese hamster ovary cells were
      stably transfected with either wild-type (WT) or mutant Gsalpha proteins (R201C
      and R201H). Stable cell lines with equivalent transfected Gsalpha protein
      expression that had relatively lower (WT) or higher (R201C and R201H) cAMP levels
      were generated. These cell lines were used to develop a fluorescence resonance
      energy transfer (FRET)-based cAMP assay in 1536-well microplate format for high
      throughput screening of small molecule libraries. A small molecule library of
      343,768 compounds was screened to identify modulators of gsp activity. A total of
      1,356 compounds with inhibitory activity were initially identified and
      reconfirmed when tested in concentration dose responses. Six hundred eighty-six
      molecules were selected for further analysis after removing cytotoxic compounds
      and those that were active in forskolin-induced WT cells. These molecules were
      grouped by potency, efficacy, and structural similarities to yield 22 clusters
      with more than 5 of structurally similar members and 144 singleton molecules.
      Seven chemotypes of the major clusters were identified for further testing and
      analyses. 

PMID- 24667242
TI  - Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical
      cords of gestational diabetic mothers reveals candidate sites for an epigenetic
      modulation of specific gene expression.
AB  - Within the complex pathological picture associated to diabetes, high glucose (HG)
      has "per se" effects on cells and tissues that involve epigenetic reprogramming
      of gene expression. In fetal tissues, epigenetic changes occur genome-wide and
      are believed to induce specific long term effects. Human umbilical vein
      endothelial cells (HUVEC) obtained at delivery from gestational diabetic women
      were used to study the transcriptomic effects of chronic hyperglycemia in fetal
      vascular cells using Affymetrix microarrays. In spite of the small number of
      samples analyzed (n=6), genes related to insulin sensing and extracellular matrix
      reorganization were found significantly affected by HG. Quantitative PCR analysis
      of gene promoters identified a significant differential DNA methylation in TGFB2.
      Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates
      recent evidences suggesting that epigenetic reprogramming of gene expression
      occurs with persistent HG and provides a background for future investigations
      addressing genomic consequences of chronic HG. 

PMID- 24667244
TI  - YuGene: a simple approach to scale gene expression data derived from different
      platforms for integrated analyses.
AB  - Gene expression databases contain invaluable information about a range of cell
      states, but the question "Where is my gene of interest expressed?" remains one of
      the most difficult to systematically assess when relevant data is derived on
      different platforms. Barriers to integrating this data include disparities in
      data formats and scale, a lack of common identifiers, and the disproportionate
      contribution of a platform to the 'batch effect'. There are few purpose-built
      cross-platform normalization strategies, and most of these fit data to an
      idealized data structure, which in turn may compromise gene expression
      comparisons between different platforms. YuGene addresses this gap by providing a
      simple transform that assigns a modified cumulative proportion value to each
      measurement, without losing essential underlying information on data
      distributions or experimental correlates. The Yugene transform is applied to
      individual samples and is suitable to apply to data with different distributions.
      Yugene is robust to combining datasets of different sizes, does not require
      global renormalization as new data is added, and does not require a common
      identifier. YuGene was benchmarked against commonly used normalization
      approaches, performing favorably in comparison to quantile (RMA), Z-score or rank
      methods. Implementation in the www.stemformatics.org resource provides users with
      expression queries across stem cell related datasets. Probe performance
      statistics including poorly performing (never expressed) probes, and examples of
      probes/genes expressed in a sample-restricted manner are provided. The YuGene
      software is implemented as an R package available from CRAN. 

PMID- 24667243
TI  - Identification and characterization of a subset of microRNAs in wheat (Triticum
      aestivum L.).
AB  - MicroRNAs (miRNAs) represent a class of endogenous regulator for post
      transcriptionally modulating gene expression. Elucidating complete miRNA
      repertoires for individual species is a long-desired goal in miRNA research. So
      far only 42 have been annotated for common wheat (Triticum aestivum) due to its
      large genome. Here, we employed miRDeep-P, a program developed previously for
      retrieving miRNAs from deep sequencing data in plants, to parse 14 sequenced
      small RNA libraries of wheat using expression sequence tags (ESTs) as the
      reference in lieu of a complete genome sequence. This effort identified 145
      miRNAs along with the corresponding stem-looped precursors with many
      differentially expressed in development and associated with powdery mildew
      infection. Examination of the phylogenetic distribution of these miRNAs and their
      target genes revealed that many are conserved in monocots. The set of miRNAs
      identified in this study is thus useful to further miRNA research in wheat and
      other important cereal crop species. 

PMID- 24667245
TI  - Comparative transcriptome analysis of sex pheromone glands of two sympatric
      lepidopteran congener species.
AB  - Two internal apple feeders of Grapholita molesta and Grapholita dimorpha share
      two major sex pheromone components (stereoisomers) and exhibit a similar
      circadian rhythm of mating behavior. This study aimed to determine the genetic
      factors diversifying these two congeners with respect to sex pheromone
      biosynthetic machinery. Transcriptomes of sex pheromone glands in both species
      were analyzed with a deep sequencing technology. To find out the gene(s)
      responsible for the stereoisomer ratios of G. molesta and G. dimorpha, a
      hypothetic sex pheromone biosynthetic pathway was predicted based on the
      transcriptomes of their sex pheromone glands. Some orthologs of Delta10
      desaturase and FARs in the synthetic pathway were specifically expressed in sex
      pheromone glands. The relatively high variation in DNA sequence and expression
      levels between G. molesta and G. dimorpha suggest their crucial roles in
      generating differential ratios of the sex pheromone stereoisomers in these two
      sympatric congeners. 

PMID- 24667247
TI  - Nutrient regulation of insulin secretion and action.
AB  - Pancreatic beta-cell function is of critical importance in the regulation of fuel
      homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus
      (DM). The beta-cell is an intricately designed cell type that couples metabolism
      of dietary sources of carbohydrates, amino acids and lipids to insulin secretory
      mechanisms, such that insulin release occurs at appropriate times to ensure
      efficient nutrient uptake and storage by target tissues. However, chronic
      exposure to high nutrient concentrations results in altered metabolism that
      impacts negatively on insulin exocytosis, insulin action and may ultimately lead
      to development of DM. Reduced action of insulin in target tissues is associated
      with impairment of insulin signalling and contributes to insulin resistance (IR),
      a condition often associated with obesity and a major risk factor for DM. The
      altered metabolism of nutrients by insulin-sensitive target tissues (muscle,
      adipose tissue and liver) can result in high circulating levels of glucose and
      various lipids, which further impact on pancreatic beta-cell function, IR and
      progression of the metabolic syndrome. Here, we have considered the role played
      by the major nutrient groups, carbohydrates, amino acids and lipids, in mediating
      beta-cell insulin secretion, while also exploring the interplay between amino
      acids and insulin action in muscle. We also focus on the effects of altered lipid
      metabolism in adipose tissue and liver resulting from activation of inflammatory
      processes commonly observed in DM pathophysiology. The aim of this review is to
      describe commonalities and differences in metabolism related to insulin secretion
      and action, pertinent to the development of DM. 

PMID- 24667246
TI  - Interleukin-6 secretion by astrocytes is dynamically regulated by PI3K-mTOR
      calcium signaling.
AB  - After contusion spinal cord injury (SCI), astrocytes become reactive and form a
      glial scar. While this reduces spreading of the damage by containing the area of
      injury, it inhibits regeneration. One strategy to improve the recovery after SCI
      is therefore to reduce the inhibitory effect of the scar, once the acute phase of
      the injury has passed. The pleiotropic cytokine interleukin-6 (IL-6) is secreted
      immediately after injury and regulates scar formation; however, little is known
      about the role of IL-6 in the sub-acute phases of SCI. Interestingly, IL-6 also
      promotes axon regeneration, and therefore its induction in reactive astrocytes
      may improve regeneration after SCI. We found that IL-6 is expressed by astrocytes
      and neurons one week post-injury and then declines. Using primary cultures of rat
      astrocytes we delineated the molecular mechanisms that regulate IL-6 expression
      and secretion. IL-6 expression requires activation of p38 and depends on NF
      kappaB transcriptional activity. Activation of these pathways in astrocytes
      occurs when the PI3K-mTOR-AKT pathway is inhibited. Furthermore, we found that an
      increase in cytosolic calcium concentration was necessary for IL-6 secretion. To
      induce IL-6 secretion in astrocytes, we used torin2 and rapamycin to block the
      PI3K-mTOR pathway and increase cytosolic calcium, respectively. Treating injured
      animals with torin2 and rapamycin for two weeks, starting two weeks after injury
      when the scar has been formed, lead to a modest effect on mechanical
      hypersensitivity, limited to the period of treatment. These data, taken together,
      suggest that treatment with torin2 and rapamycin induces IL-6 secretion by
      astrocytes and may contribute to the reduction of mechanical hypersensitivity
      after SCI. 

PMID- 24667248
TI  - Development of repeated sprint ability in talented youth basketball players.
AB  - Factors affecting repeated sprint ability (RSA) were evaluated in a mixed
      longitudinal sample of 48 elite basketball players 14-19 years of age (16.1 +/-
      1.7 years). Players were observed on 6 occasions during the 2008-09 and 2009-10
      seasons. Three following basketball-specific field tests were administered on
      each occasion: the shuttle sprint test for RSA, the vertical jump for lower body
      explosive strength (power), and the interval shuttle run test for interval
      endurance capacity. Height and weight were measured; body composition was
      estimated (percent fat, lean body mass). Multilevel modeling of RSA development
      curve was used with 32 players (16.0 +/- 1.7 years) who had 2 or more
      observations. The 16 players (16.1 +/- 1.8 years) measured on only 1 occasion
      were used as a control group to evaluate the appropriateness of the model. Age,
      lower body explosive strength, and interval endurance capacity significantly
      contributed to RSA (p <= 0.05). Repeated sprint ability improved with age from 14
      to 17 years (p <= 0.05) and reached a plateau at 17-19 years. Predicted RSA did
      not significantly differ from measured RSA in the control group (p >= 0.05). The
      results suggest a potentially important role for the training of lower body
      explosive strength and interval endurance capacity in the development of RSA
      among youth basketball players. Age-specific reference values for RSA of youth
      players may assist basketball coaches in setting appropriate goals for individual
      players.

PMID- 24667249
TI  - Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in
      a human xenograft model.
AB  - OBJECTIVE: Uterine serous carcinoma (USC) represents an aggressive subtype of
      endometrial cancer. We sought to understand Notch pathway activity in USC and
      determine if pathway inhibition has anti-tumor activity. METHODS: Patient USC
      tissue blocks were obtained and used to correlate clinical outcomes with Notch1
      expression. Three established USC cell lines were treated with gamma-secretase
      inhibitor (GSI) in vitro. Mice harboring cell line derived or patient derived USC
      xenografts (PDXs) were treated with vehicle, GSI, paclitaxel and carboplatin
      (P/C), or combination GSI and P/C. Levels of cleaved Notch1 protein and Hes1 mRNA
      were determined in GSI treated samples. Statistical analysis was performed using
      the Wilcoxon rank sum and Kaplan-Meier methods. RESULTS: High nuclear Notch1
      protein expression was observed in 58% of USC samples with no correlation with
      overall survival. GSI induced dose-dependent reductions in cell number and
      decreased levels of cleaved Notch1 protein and Hes1 mRNA in vitro. Treatment of
      mice with GSI led to decreased Hes1 mRNA expression in USC xenografts. In
      addition, GSI impeded tumor growth of cell line xenografts as well as UT1 USC
      PDXs. When GSI and P/C were combined, synergistic anti-tumor activity was
      observed in UT1 xenografts. CONCLUSIONS: Notch1 is expressed in a large subset of
      USC. GSI-mediated Notch pathway inhibition led to both reduced cell numbers in
      vitro and decreased tumor growth of USC some xenograft models. When combined with
      conventional chemotherapy, GSI augmented anti-tumor activity in one USC PDX line
      suggesting that targeting of the Notch signaling pathway is a potential
      therapeutic strategy for future investigation.

PMID- 24667250
TI  - Low expression of long noncoding XLOC_010588 indicates a poor prognosis and
      promotes proliferation through upregulation of c-Myc in cervical cancer.
AB  - OBJECTIVE: The identification and investigation of cancer-associated long non
      coding RNAs are important for understanding the molecular biology of cancer. The
      aim of the present study was to examine the expression pattern of lncRNA
      XLOC_010588 in cervical cancer and to evaluate its biological role and clinical
      significance in tumor progression. METHODS: We examined the expression of
      XLOC_010588 in 218 cervical cancer tissues and matched 218 adjacent normal
      tissues using real-time qRT-PCR. Over-expression and RNA interference approaches
      were used to investigate the biological functions of XLOC_010588. The effect of
      XLOC_010588 on proliferation was evaluated by MTT and BrdU assays. Western blot
      assays were used to investigate the molecular mechanism by which XLOC_010588
      increases cervical cancer cell proliferation. RESULTS: The results showed that
      XLOC_010588 expression in cervical cancer was significantly downregulated.
      Decreased XLOC_010588 expression was correlated with FIGO stage, tumor size and
      SCC-Ag. Moreover, cervical cancer patients with XLOC_010588 lower expression have
      shown poorer prognosis. Multivariate Cox regression analyses showed that
      XLOC_010588 expression served as an independent predictor for overall survival.
      Ectopic expression of XLOC_010588 inhibited the proliferation of HeLa and SiHa
      cells. By contrast, knockdown of XLOC_010588 promoted the growth of HCC94 cells.
      Western blot assays confirmed that XLOC_010588 physically associates with c-Myc,
      consequently decreasing the expression of c-Myc. The expression of XLOC_010588
      and c-Myc is strongly correlated in cervical cancer tissues. CONCLUSION: These
      results suggested that XLOC_010588 plays a pivotal role in cervical cancer cell
      proliferation via decreasing c-Myc expression and implicated the potential
      application of XLOC_010588 in cervical cancer therapy.

PMID- 24667252
TI  - [Screening and establishment of human lung cancer cell lines with organ-specific
      metastasis potential].
AB  - BACKGROUND: Cancer metastasis is not only the malignant marker and
      characteristics, but also the main cause of failure to cure and lose their life
      in the patients with lung cancer. Lung cancer metastasis has organ-specific
      characteristics. The most common sites of lung cancer metastasis are mediastinal
      lymph node, brain, bone, liver and adrenal gland. The aim of this study is to
      screen and establish lung cancer cell model with organ-specific metastasis
      potential with human high-metastatic large cell lung cancer cell line L9981
      established by our laboratory previously, and to provide cell models for studying
      the mechanisms and signal regulation of organ-specific metastasis of lung cancer.
      METHODS: The parent lung cancer cell line, L9981-Luc, was inoculated in the
      armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect
      the lung cancer organ-specific metastasis every week. When the organ-specific
      metastasis were established, the nude mices bearing the lung cancer were
      sacrificed when they became moribund. Under sterile conditions, the organs
      (mediastinal lymph nodes, lung, spinal column and brain) with lung cancer organ
      specific metastasis were removed and the metastasized nodules were dissected free
      of connective tissue and blood clots, and rinsed twice with medium. The
      metastasized nodules were finely minced using sterile scalpel blades in medium,
      and the cells were seeded in tissue culture dishes. Then, the cells with organ
      specific metastasis potential were reinoculated into the armpit of nude mice,
      respectively. This processes were repeated to establish the organ-specific
      metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ
      specific metastasis sublines of L9981-Luc were screened and established, which
      the four cell lines have the characteristics only metastasized to brian, lung,
      bone and mediastinal lymph node. RESULTS: A group of organ-specific metastasis
      cell lines which only metastasized to brian, lung, bone and mediastinal lymph
      node were successfully established through repeating reinoculatation, live animal
      imaging in nude mice, and screening and identification in vitro. We named the
      four cell lines as L9981-BoM, L9981-LuM, L9981-BrM and L9981-LnM, respectively.
      The L9981-BoM cell was only metastasized to bone. The l9981-LuM cell was only
      metastasized to lung. The L9981-BrM only metastasized to brain. The L9981-LnM
      cell was only metastasized to midiastinal lymph nodes. CONCLUSIONS: A human large
      cell lung cancer cell model with bone, lung, brain and lymph node-specific
      metastasis potential was successfully established. It will be helpful to further
      study the molecular mechanisms and signal regulation of lung cancer organ-
      specific metastasis. It will be to also provide reliable cell model for
      developing new techniques and molecular targeting drugs of inhibiting or
      reversing lung cancer metastasis.

PMID- 24667251
TI  - A framework for organizing cancer-related variations from existing databases,
      publications and NGS data using a High-performance Integrated Virtual Environment
      (HIVE).
AB  - Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD,
      RefSeq and other database biocurators has led to a rich repository of information
      on functional sites of genes and proteins. This information along with variation
      related annotation can be used to scan human short sequence reads from next
      generation sequencing (NGS) pipelines for presence of non-synonymous single
      nucleotide variations (nsSNVs) that affect functional sites. This and similar
      workflows are becoming more important because thousands of NGS data sets are
      being made available through projects such as The Cancer Genome Atlas (TCGA), and
      researchers want to evaluate their biomarkers in genomic data. BioMuta, an
      integrated sequence feature database, provides a framework for automated and
      manual curation and integration of cancer-related sequence features so that they
      can be used in NGS analysis pipelines. Sequence feature information in BioMuta is
      collected from the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar,
      UniProtKB and through biocuration of information available from publications.
      Additionally, nsSNVs identified through automated analysis of NGS data from TCGA
      are also included in the database. Because of the petabytes of data and
      information present in NGS primary repositories, a platform HIVE (High
      performance Integrated Virtual Environment) for storing, analyzing, computing and
      curating NGS data and associated metadata has been developed. Using HIVE, 31 979
      nsSNVs were identified in TCGA-derived NGS data from breast cancer patients. All
      variations identified through this process are stored in a Curated Short Read
      archive, and the nsSNVs from the tumor samples are included in BioMuta.
      Currently, BioMuta has 26 cancer types with 13 896 small-scale and 308 986 large
      scale study-derived variations. Integration of variation data allows
      identifications of novel or common nsSNVs that can be prioritized in validation
      studies. Database URL: BioMuta:
      http://hive.biochemistry.gwu.edu/tools/biomuta/index.php; CSR:
      http://hive.biochemistry.gwu.edu/dna.cgi?cmd=csr; HIVE:
      http://hive.biochemistry.gwu.edu.

PMID- 24667253
TI  - [Construction and expression of nm23-H1 gene with different enzyme activities and
      resistant specific shRNA in eukaryotic expression vector].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that nm23-H1 gene was a tumor
      metastatic suppressor gene. However, it's molecular mechanism of suppressing
      metastasis remains unexplored. There is a closely relationship between the
      abnormality of stucturs and functions of nm23-H1 gene, and cancer invasion and
      metastasis. We have constructed the vector with nm23-H1-shRNA and the vector with
      nm23-H1cDNA resistant to the specific shRNA. So, we plan to construct shRNA
      resistant eukaryotic expression vector of nm23-H1 gene by site-directed
      mutagenesis, rescue experiment was performed to verify the nm23-H1 gene
      expression, and to provide basement for studying the biochemical mechanisms of
      nm23-H1 gene. METHODS: Site-directed mutagenesis of nm23-H1 gene was performed by
      overlap extension PCR method. Pure plasmid containing gene of nm23-H1 (shRNA
      resistant) was prepared. The desired five mutations were constructed and cloned
      into the eukaryotic vector pcDNA3.1Hygro(+). The human lung adenocarcinoma cell
      A549/nm23-H1-shRNA (stable nm23-H1 gene silencing) was transfected with the five
      mutants, and the expression of the mutant proteins was determined by Western
      blot. RESULTS: Five eukaryotic expression vectors (shRNA-resistant) of nm23-H1,
      nm23-H1S44A, nm23-H1(P96S), nm23-H1(H118F), nm23-H1(S120G), nm23-H1(P96S-S120G),
      were successfully constructed. The results of DNA sequencing confirmed that the
      base sequences of the genes were completely concordant with experiment design.
      The expression of nm23-H1 mutant proteins was verified by Western blot.
      CONCLUSION: Five eukaryotic expression vectors (shRNA-resistant) of nm23-H1 gene
      were successfully constructed, and the mutant proteins were verified. The site
      directed mutagenesis technical of overlap extension PCR is a efficient, simple
      and economical method.

PMID- 24667254
TI  - [Radio-labeling of T7 peptide with 99mTc and its biodistribution in nude mice
      bearing non-small cell lung cancer].
AB  - BACKGROUND: Lung cancer is a malignant tumor with high mortality rates. This
      study aims to develop potential candidates of integrin alphavbeta3 imaging
      agents, which can facilitate the diagnosis and treatment of lung cancer. METHODS:
      The T7 peptide was labeled with carbonyl technetium. The thin layer
      chromatography with acetone as the development system was performed to
      investigate the purity and stability of (99m)Tc-T7. The binding affinity of
      (99m)Tc-T7 with NCI-H157 tumor cells was determined. The biodistribution of
      (99m)Tc-T7 in nude mice bearing non-small cell lung carcinoma was observed after
      injection of (99m)Tc-T7 at 0.5 h, 1 h, 2 h, 4 h, and 8 h, and the radioactive
      ratio of tumor (T) and non-tumor tissues (NT) was calculated. RESULTS: 99mTc
      labeled T7 had high radiochemical purity of more than 90%, which does not require
      further purification, with good stability in vitro. The association and
      dissociation constant (KD) of (99m)Tc-T7 with NCI-H157 tumor cells was 196.1 nM.
      (99m)Tc-T7 was mainly metabolism through the internal organs with rapid blood
      removal. Moreover, the uptake in tumor tissue was significantly higher than the
      muscle with tumor/muscle ratio of 5.8. In addition, the (99m)Tc-T7 exhibited a
      transient accumulation in the lungs. CONCLUSIONS: The (99m)Tc-T7 could be
      prepared using a simple method, had high labeling rate and good stability, and
      could be accumulated at tumor site. Thus, (99m)Tc-T7 is a potential lung cancer
      SPECT/CT imaging agent.

PMID- 24667255
TI  - [Application of the Ca2+ indicator fluo-3 and fluo-4 in the process of H2O2
      induced apoptosis of A549 cell].
AB  - BACKGROUND AND OBJECTIVE: Lung cancer is a common malignant tumor all over the
      world, and Ca(2+) is a critical regulator for apoptosis of cancer cells. The
      monitoring of cytoplastic Ca(2+) level in real-time will contribute to further
      investigate the molecular mechanisms of apoptosis mediated by Ca2+ in lung cancer
      cells. To evaluate the Ca(2+) indicator fluo-3 and fluo-4 in the process of H2O2
      induced the apoptosis of lung adenocarcinoma A549 cells. The cytoplastic Ca(2+)
      concentration ([Ca(2+)]i) was determined in real-time, and the correlations
      between [Ca(2+)]i and cell apoptosis were investigated. The differences in
      fluorescence intensity and measured value were compared between the two Ca(2+)
      indicators. METHODS: Cells were loaded with the Ca(2+) indicator fluo-3 or fluo-4
      for 1 h, and then stimulated with 50 mM H2O2. Laser scanning confocal microscope
      was applied to perform real-time monitoring on the variation of [Ca(2+)]i in
      selected cells. DAPI staining was used to observe apoptosis in H2O2 treated
      cells. RESULTS: Our results showed that the fluorescence intensity of fluo-4 was
      stronger than that of fluo-3 in the same condition of dye concentration, loading
      time and image acquisition parameters before or after H2O2 stimulation. The
      cytoplastic [Ca(2+)]i was rapidly elevated in H2O2 stimulated A549 cells. The
      range of [Ca(2+)]i in selected cells loaded with fluo-3 was 112.2 nM-1,069.6 nM,
      and that in selected cells loaded with fluo-4 was 7.6 nM-505.4 nM. Moreover, the
      apoptotic rate was significantly increased in H2O2 treated cells, compared with
      untreated ones (P<0.01). CONCLUSION: In summary, H2O2 promoted Ca(2+) release in
      A549 cells, and induced cell apoptosis. Ca(2+) indicator fluo-4 was probably more
      applicable to measure [Ca(2+)]i in cells with less content of Ca(2+).

PMID- 24667256
TI  - [Occurrence and survival condition of lung cancer with different histologies
      among residents in Pudong new area].
AB  - BACKGROUND: Different histologies of lung cancer vary in occurrence and
      prognosis. This study aims to analyze the incidence and occurrence trend of lung
      cancer and investigate the survival rate and its influential factors among lung
      cancer patients with different histologies. METHODS: Permanent residents were
      recruited between 2002 and 2009 in Pudong New Area (former Nanhui Area and former
      Pudong Area), Shanghai, China. Annual percent changes were estimated by a linear
      regression of the logarithm on the incidence rates for eight years. Survival
      rates were calculated and compared by using life-table analysis and Log-rank
      test, respectively. RESULTS: The standardized incidence rates of lung cancer were
      52.28 and 18.86 per 100,000 in males and females, respectively. The median
      survival time was 410.72 days for specific classified lung cancer. The incidence
      rates of adenocarcinoma ranked the highest and showed an upward tendency
      (P<0.05). Patients with small cell lung cancer showed the worst survival
      condition. The survival condition in males with squamous cell lung cancer living
      in former Nanhui Area was better compared with those living in former Pudong
      Area. CONCLUSIONS: Lung cancers with different histologies demonstrated different
      occurrence trends and survival rates. Gender, age, and living area influence the
      survival rates of lung cancer with different histologies.

PMID- 24667257
TI  - [A study on quality of life after thoracoscopic assistant lobectomy for lung
      cancer].
AB  - BACKGROUND: Conventional radical surgeries for lung cancer incur a large amount
      of trauma, thoracoscopic surgeries can reduce trauma, and hopefully improve
      patients' postoperative quality of life (QOL). The aim of this study is to
      evaluate the impact of thoracoscopic radical surgeries on quality of life of
      patients with non-small cell lung cancer (NSCLC). METHODS: Use Quality of Life
      Core 30 Questionnaire (QLQ-C30) which was exploited by European Organization for
      Research and Treatment (EORTC) and Quality of Life-Lung Cancer 13 Questionnaire
      (QLQ-LC13) which is the supplementary questionnaire according to the lung cancer
      patients to evaluate QOL of 60 NSCLC patients in thoracoscopic surgery group and
      conventional surgery group from 3 days before operation to 24 weeks after
      operation. RESULTS: A total of 215 questionnaires were collected from 60
      patients; 25 postoperative questionnaires were not completed because patients
      could not be contacted for follow-up visits. QOL declined markedly in all
      patients at 3 days postoperatively; preoperative and 3-day postoperative global
      QOL scores in the conventional surgery and thoracoscopic surgery group were 87.8
      +/- 10.3 vs 38.3 +/- 13.1 (P<0.001) and 82.7 +/- 9.6 vs 56.3 +/- 14.8 (P<0.001),
      respectively. Thereafter, QOL recovered gradually in all patients. Patients who
      underwent open surgery showed the most pronounced decline in QOL; global scores
      were lower in this group than in the thoracoscopic surgery group (P=0.012,9) at 3
      days postoperatively and was not restored to the preoperative level at 24 weeks
      postoperatively (P=0.012,4). QOL declined less in patients undergoing
      thoracoscopic surgery, and most indices had recovered to preoperative levels at
      24 weeks postoperatively. CONCLUSIONS: With the advantages of small trauma,
      faster recovery and higher postoperative QOL, thoracoscopic surgery is a
      preferable lung cancer surgery.

PMID- 24667258
TI  - [The value of transbronchial needle aspiration combined with rapid on-site
      evaluation of cytology in the diagnosis of lung cancer].
AB  - BACKGROUND: There have been several studys about transbronchial needle aspiration
      (TBNA) combined with rapid on-site evaluation (ROSE) so far at home and abroad,
      yet few studys were especially for patients with lung cancer. The aim of our
      study is to investigate the effect of TBNA combined with ROSE in the diagnosis of
      lung cancer. METHODS: The data of the patients from December 2012 to December
      2013, who were performed with TBNA and ultimately diagnosed with lung cancer in
      the People's Hospital of Binzhou City, were retrospectively analyzed. The
      patients were divided into two groups, ROSE group (rapid on-site evaluation
      group) and no-ROSE group (the group without rapid on-site evaluation). Among
      these patients, 37 patients were in the ROSE group and 32 patients were in the no
      ROSE group. The result of ROSE and HE stain, the diagnostic yields and needle
      passes of each lymph node, the complication and cytology diagnostic cost of TBNA
      with ROSE and without ROSE were compared. RESULTS: The coherence of ROSE and HE
      stain was 94.1% (32/34). The diagnostic yields of TBNA were 91.9% (34/37) and
      78.1% (25/32) in ROSE group and no-ROSE group respectively, no significant
      differences were found. But the median number of needle passes of each lymph node
      and the percentage of the complication in ROSE group and no-ROSE group was
      significantly lower (t=29.5, P<0.05 and chi(2)=4.4, P<0.05, respectively). The
      cytopathological diagnostic cost of ROSE group was significantly lower compared
      with no-Rose group (t=10.9, P<0.05). CONCLUSIONS: TBNA combined with ROSE has
      good concordance with HE stain in the diagnosis of lung cancer, and could reduce
      the needle passes, cytopathological diagnostic cost and complication, worthy of
      popularized.

PMID- 24667259
TI  - [Expression of MiRNA-221 in non-small cell lung cancer tissues and correlation
      with prognosis].
AB  - BACKGROUND: MicroRNAs were important regulators of tumors and the expression of
      miRNA-221 was associated with malignant proliferation and invasion in many
      tumors. The aim of this study is to explore the expression of miRNA-221 in non
      small cell lung cancer (NSCLC) tissues and its correlation with prognosis.
      METHODS: We retrospectively analyzed the clinical characteristics of 117 NSCLC
      patients who underwent surgery in our hospital from November 2005 to January
      2007. Real-time PCR was used to detect the expression of miRNA-221. Chi-square
      test was utilized to analyze the relationship between miRNA-221 expression and
      clinicopathologic features. Survival curves were plotted by using the Kaplan
      Meier method and compared by the Log-rank test. A Cox proportional hazard
      regression model was applied to examine the joint effect of covariants. A P-value
      less than 0.05 was evaluated as statistically significant. RESULTS: The patients
      were divided into two groups according to the relatively expression of miRNA-221.
      No statistically significance was observed between the expression of miRNA-221
      and the clinicopathologic parameters, including gender (chi(2)=0.070, P=0.791),
      histology (chi(2)=0.414, P=0.520), p-TNM stage (chi(2)=0.068, P=0.794) and
      history of smoking (chi(2)=0.206, P=0.650). Kaplan-Meier analysis showed that
      high expression of miRNA-221 was closely associated with a shorter survival time
      (P<0.001). Finally, both univariate and multivariate analyses demonstrated that
      high miRNA-221 expression might be a poor prognostic marker of NSCLC patients.
      CONCLUSIONS: Our results indicated that down-regulation of miRNA-221 was
      associated with poor prognosis of patients with NSCLC. MiRNA-221 may serve as a
      molecular prognosis marker for patients with NSCLC.

PMID- 24667260
TI  - [The research of clinical pathological features of ALK positive lung cancer in
      525 patients and the discussion of detection methods].
AB  - BACKGROUND: The fusion (rearrangement) of anaplastic lymphoma kinase (ALK) gene
      has been identified as an import factor to the tumorigenesis and development of
      lung cancer. ALK tyrosine kinase inhibitors (ALK-TKIs) have been proved to have
      good effects to ALK positive lung cancers. The increasement of the relevance
      ratio of ALK will be very important to patients. The aim of this study is to
      investigate the clinical pathological features of ALK positive lung cancer, and
      the roles of immunohistochemistry (IHC) and fluorescence in situ hybridization
      (FISH) in screening and confirming the ALK positive cases in the testing flow of
      ALK. METHODS: IHC analysis of ALK in tumor specimens was performed on 525 lung
      cancer patients. 34 cases among them were confirmed by FISH. RESULTS: The
      positive incidence of ALK by IHC was 5.14% (27/525). The ALK positive patients
      were significantly younger than ALK negative patients (P<0.05), and femal was
      predominant (P<0.05). The proportion of solid predominant adenocarcinoma was
      significantly higher in ALK positive patients (P<0.05). While acinar and lepidic
      predominant adenocarcinoma were significantly lower in ALK positive patients
      (P<0.05). FISH was applied in 34 cases. The coincidence rate was increased with
      the increasement of positive intensity of IHC staining. All the IHC positive
      cases with or without EGFR mutation must be confirmed by FISH. CONCLUSIONS: IHC
      is a reliable detection method to screening the ALK in lung cancer, and then
      enhance the relevance ration. To make a definite diagnosis of ALK positive lung
      cancer, FISH is a significant detection method.

PMID- 24667261
TI  - [The relationship between FHIT gene promoter methylation and lung cancer risk: a
      meta-analysis].
AB  - BACKGROUND: Tumor-suppressor gene promoter DNA methylation in tumor cells is
      associated with its reduced expression. FHIT (fragile histindine triad) was one
      of the important tumor suppressor genes which was found hypermethylated in the
      promoter region in most of tumors. The aim of this study is to evaluate the
      relationship between FIHT gene promother methylation and lung cancer risk by meta
      analysis. METHODS: By searching Pubmed, CNKI and Wanfang, the open published
      articles related to FHIT gene promoter methylation and lung carcinoma risk were
      collected. The odds ratio (OR) and range of FHIT gene of cancer tissue of lung
      cancer patients compared with normal lung tissue, plasma and the bronchial lavage
      fluid were pooled by statistical software Stata 11.0. RESULTS: Eleven studies
      were finally included in this meta-analysis. The median methylation rate were
      P(median)=40.0% (0-68.3%), P(median)=8.7% (0-35.0%), P(media)n=33.3% (17.1%
      38.3%) and P(median)=35.9% (31.1%-50.8%) in cancer tissue, NLT, BALF and plasm
      respectively. The pooled results showed the methylation rate in tumor tissue was
      much higer than that of NLT OR=5.82 (95%CI: 3.74-9.06, P<0.05), but without
      statistical significance for BALF OR=1.55 (95%CI: 0.89-2.70, P>0.05) and plasma
      OR=1.41 (95%CI: 0.90-2.20, P>0.05). CONCLUSIONS: Hypermethylation of FHIT gene
      promoter region was found more frequent in cancer tissue than that of NLT which
      may demonstrated association between lung cancer risk and FHIT gene promoter
      methylation.

PMID- 24667262
TI  - [High resolution melting curve method for detection of BIM deletion].
AB  - BACKGROUND: The aim of this study is to establish a HRM (high resolution melting
      curve) method for detection of deletion in human BIM gene and to detect this site
      deletion with the above method in 30 lung cancer samples and 30 normal samples.
      METHODS: The primers for detection of BIM deletion were designed and synthesized.
      The HRM method for geng deletion was established. And select the part of samples
      to detect BIM delection by normal PCR and sequencing assay. The Tm value of wild
      type PCR products was higher than that of the deletion PCR products. The
      difference of the corresponding Tm value is 2.5 oC. RESULTS: By detection with
      HRM methods, 1 samples were confirmed to be mutant, 7 samples were confirmed to
      be heterozygous and the other 22 samples were all wild type in the lung cancer
      samples. 2 samples were confirmed to be heterozygous and the other 28 samples
      were all wild type in the normal samples. CONCLUSIONS: The HRM method for
      detection of BIM deletion established in this study is a sensitive, accurate,
      simple and high throughput method.

PMID- 24667263
TI  - [Clinicopathological and prognostic significance of a panel of tumor biomarkers
      in lung adenocarcinoma: a tissue microarray study].
AB  - BACKGROUND: Lung adenocarcinoma is one of the most common histological subtypes
      of lung cancer. The incidence of this disease was continuously increased. This
      study aims to detect the expressions of Napsin A, TTF-1, ERCC1, RRM1, EGFR, HER2,
      ERalpha, ERbeta, PR, and Bcl-2 in lung adenocarcinoma and to explore their
      correlations with clinicopathological characteristics and prognosis. METHODS: A
      total of 227 lung adenocarcinoma specimens were constructed in tissue
      microarrays. The expressions of the 10 tumor biomarkers were analyzed by
      immunohistochemistry on paraffin-embedded sections. RESULTS: Among the 10
      markers, Napsin A was gender-related (P=0.049). Napsin A, PR, and EGFR were
      significantly associated with smoking. TTF-1 and ERCC1 were closely associated
      with tumor size. Napsin A, TTF-1, ERalpha, and PR were remarkably associated with
      tumor differentiation. TTF-1, Bcl-2, and ERCC1 were closely associated with tumor
      stage (P<0.05). No marker was related to age. No correlations were observed
      between ERbeta, HER2, and RRM1 expressions and clinicopathological parameters
      (P>0.05). Univariate analysis results showed that Napsin A, TTF-1, and ERCC1 were
      significantly associated with overall survival. TTF-1 was remarkably associated
      with disease-free survival (P<0.05). Stage I cases were further analyzed and
      revealed that only Napsin A expression was associated with overall survival
      (P<0.05). No marker was correlated with disease-free survival (P>0.05).
      Multivariate analysis results showed that pathological staging was significantly
      associated with overall survival and disease-free survival (P<0.05). No marker
      was identified as a predictor of patient outcome (P>0.05). CONCLUSIONS: Napsin A,
      TTF-1, and ERCC1 are the markers indicating good prognosis of lung
      adenocarcinoma.

PMID- 24667264
TI  - [Clinical features in 23 lung cancer patients complicated with pulmonary
      thromboembolism].
AB  - BACKGROUND: Malignant tumors are often complicated with pulmonary thromboembolism
      (PTE), particularly in lung cancer (LC). This study investigated the clinical
      characteristics, risk factors, and survival time of patients with PTE and LC.
      METHODS: We retrospectively reviewed the clinical data of patients with LC in
      Medical Oncology of Tianjin Medical University General Hospital between June 2009
      and July 2013. A total of 23 patients suffered from both PTE and LC. A total of
      46 cases were used as control subjects. The survival of these patients was
      compared with that of the control subjects by Kaplan-Meier analysis. RESULTS: A
      total of 1128 cases were diagnosed with LC, in which 23 were clearly diagnosed
      with PTE, and 16 (69.6%) patients who suffered from both LC and PTE developed
      adenocarcinoma. These patients also exhibited a higher incidence of unexplained
      dyspnea than those who were diagnosed with LC only (P<0.01). The patients with
      both PTE and LC displayed lower counts of hemoglobin (Hb), albumin (ALB), and
      blood oxygen pressure (PO2) than those with LC only (P<0.05). The patients with
      both PTE and LC also exhibited higher counts of leukocyte (WBC) and D-dimer than
      those with LC only (P<0.05). No statistical difference was found between the two
      groups in terms of platelet counts, glutamic pyruvic transaminase level, and
      glutamic oxaloacetic transaminase level (P>0.05). Ten cases (43.48%) with deep
      venous thrombosis were observed in the PTE and LC group, and six patients
      (26.09%) were at a high risk of acute pulmonary embolism. Hb<100 g/L, WBC>11 *
      10(9)/L, D-Dimer>500 ng/ml, PO2<80 mmHg, ALB<30 g/L were the risk factors of LC
      with PTE (odds ratio values were listed as follows: 5.50, 11.03, 4.83, 4.68,
      9.63, respectively). On July 29, 2013, the median survival time of patients with
      PTE and LC was 7.77 months. This result was significantly lower than that (19.27
      months) of patients with LC only (P=0.02). The survival time of patients
      suffering from both LC and PTE and undergoing chemotherapy was higher than that
      of patients who did not undergo such treatment. CONCLUSIONS: The common
      pathological type observed in patients with both LC and PTE was adenocarcinoma.
      The common clinical manifestations were unexplained dyspnea and cough. The first
      five months after LC diagnosis corresponded to a high period of PTE. Patients
      with LC and PTE exhibited less survival time. As such, chemotherapy is beneficial
      for the survival of patients with LC and PTE.

PMID- 24667265
TI  - [Research progress of the relationship between tumor suppressor gene ? PTEN and
      non-small cell lung cancer].

PMID- 24667266
TI  - [Advances in hypoxia microenvironment and chemotherapy-resistant of lung cancer].
AB  - Lung cancer is one of the malignant tumors with highest incidence recently in our
      country. Tumor hypoxia phenomenon was first discovered in lung cancer. It plays
      important roles in tumor cell drug-resistance, apoptosis, invasion and
      metastasis, angiogenesis. Chemotherapy-resistant is one of the core reasons of
      treatment failure and disease progress, and many works on the study of
      chemotherapy-resistant have been done. This article reviewed the research
      progress of those mechanisms by which lung cancer hypoxia microenvironment could
      induce chemotherapy-resistance. 

PMID- 24667267
TI  - [Advances in the relationship between microRNA and cisplatin resistance of lung
      cancer].
AB  - MicroRNAs (miRNAs) are a class of small, about 22 nucleotides endogenous
      noncoding RNAs that negatively regulate their target genes' expression through
      post-transcriptional suppression. MicroRNA has a broad effect on tumorigenesis
      and tumor biological processes, including tumor development, differentiation,
      metastasis and chemoresistance. Chemoresistance represents a major obstacle in
      effective clinical treatment of tumors, how to conquer the chemoresistance in
      tumor arouses people's interst. A growing number of studies have proved that
      microRNAs play a crucial role in tumor chemoresistance. This view will discuss
      the the progress research between microRNA and tumor therapy, especially the
      cisplatin chemotherapy in tumor.

PMID- 24667269
TI  - [Advances in immunotherapies for non-small cell lung cancer].
AB  - Globally, Lung cancer is the leading cause of cancer-related death of high
      morbidity and mortality with poor prognosis, which needs some more effective and
      less toxic therapies. The immunotherapies offer a novel approach for the
      treatment of patients with non-small cell lung cancer (NSCLC) in both the
      adjuvant and palliative disease settings. A number of promising immunotherapies
      based on different mechanism have now been evaluated showing an increasing
      response rate. Moreover, further phase II/III clinical trials will be indicated
      to explore its value. These include checkpoint inhibitors (anti-CTLA4 antibody,
      anti-PD-1 antibody, anti-PD-L1 antibody), active vaccination (L-BLP25 liposome
      vaccine, Belagenpumatucel-L vaccine, MAGE-A3 protein vaccine) and adoptive
      vaccination (CIK cells). The purpose of this paper will draw a summary on the
      theory, clinical trials, toxicity and problems to be solved of the
      immunotherapies in NSCLC. 

PMID- 24667268
TI  - [Vascular normalization and cancer immunotherapy].
AB  - Immunotherapies, as a promising anticancer therapy stratrgy, has been paid more
      and more attentions. However, the abnormal tumor vasculature creates a hypoxic
      microenvironment that make immune cells toward immune suppression. The
      immunosuppressive microenvironment seems to impede the development of
      immunotherapies. Hence, normalization tumor vascular by anti-angiogenesis
      properly could improve the immunosuppressive miroenvironment. Consequently, the
      efficacy of the immunotherapies was enhanced. Here, we discuss the effects of
      vascular normalizing on tumor immunity and propose a potentially strategy to re
      engineer the tumor-immune microenvironment and improve cancer immunotherapy. 

PMID- 24667270
TI  - [Clinical diagnosis and therapy strategies of lung metastasis].

PMID- 24667271
TI  - [Postoperative nursing experience of tracheobronchial plasty].

PMID- 24667272
TI  - Dido3-dependent HDAC6 targeting controls cilium size.
AB  - Primary cilia are involved in a variety of physiological processes such as
      sensing of the environment, cell growth and development. Numerous developmental
      disorders and pathologies arise from defects in these organelles. Multiple
      proteins that promote formation and disassembly of the primary cilium have been
      identified, but little is known about the mechanisms that control steady-state
      cilium size. Here, we show that death inducer obliterator (Dido3)-dependent
      targeting of histone deacetylase 6 (HDAC6) is a key determinant of cilium size in
      growth-arrested cells. The amount of either protein negatively correlates with
      cilium size. Dido3 availability at the centrosome governs ciliary HDAC6 levels,
      and redistribution of the two proteins controls tubulin acetylation. In turn,
      basal body localization of Dido3 and HDAC6 depends on the actin network,
      previously shown to limit cilium size independent of the cell cycle. These
      results show that not only kinase-dependent activation of a deacetylase but also
      its subcellular distribution controls substrate selection. 

PMID- 24667273
TI  - Basic timing abilities stay intact in patients with musician's dystonia.
AB  - Task-specific focal dystonia is a movement disorder that is characterized by the
      loss of voluntary motor control in extensively trained movements. Musician's
      dystonia is a type of task-specific dystonia that is elicited in professional
      musicians during instrumental playing. The disorder has been associated with
      deficits in timing. In order to test the hypothesis that basic timing abilities
      are affected by musician's dystonia, we investigated a group of patients (N = 15)
      and a matched control group (N = 15) on a battery of sensory and sensorimotor
      synchronization tasks. Results did not show any deficits in auditory-motor
      processing for patients relative to controls. Both groups benefited from a pacing
      sequence that adapted to their timing (in a sensorimotor synchronization task at
      a stable tempo). In a purely perceptual task, both groups were able to detect a
      misaligned metronome when it was late rather than early relative to a musical
      beat. Overall, the results suggest that basic timing abilities stay intact in
      patients with musician's dystonia. This supports the idea that musician's
      dystonia is a highly task-specific movement disorder in which patients are mostly
      impaired in tasks closely related to the demands of actually playing their
      instrument.

PMID- 24667274
TI  - Proton-detected MAS NMR experiments based on dipolar transfers for backbone
      assignment of highly deuterated proteins.
AB  - Proton-detected solid-state NMR was applied to a highly deuterated insoluble, non
      crystalline biological assembly, the Salmonella typhimurium type iii secretion
      system (T3SS) needle. Spectra of very high resolution and sensitivity were
      obtained at a low protonation level of 10-20% at exchangeable amide positions. We
      developed efficient experimental protocols for resonance assignment tailored for
      this system and the employed experimental conditions. Using exclusively dipolar
      based interspin magnetization transfers, we recorded two sets of 3D spectra
      allowing for an almost complete backbone resonance assignment of the needle
      subunit PrgI. The additional information provided by the well-resolved proton
      dimension revealed the presence of two sets of resonances in the N-terminal helix
      of PrgI, while in previous studies employing (13)C detection only a single set of
      resonances was observed. 

PMID- 24667275
TI  - A guide to prepare patients with inflammatory bowel diseases for anti-TNF-alpha
      therapy.
AB  - Current therapy of moderate-to-severe inflammatory bowel disease (IBD) often
      involves the use of anti-tumor necrosis factor alpha (TNF-alpha) agents. Although
      very effective, theses biologics place the patient at increased risk for
      developing infections and lymphomas, the latter especially when in combination
      with thiopurines. Appropriate patient selection, counseling, and education are
      all important features for the successful use of anti-TNF-alpha therapy. A
      thorough history to rule-out contraindications of this therapy and emphasis on
      monitoring guidelines are important steps preceding administration of anti-TNF
      alpha agents. This therapy should only be considered if a recent evaluation has
      established that the patient has active IBD. In addition, it is important to
      exclude disease mimickers. Anti-TNF-alpha agents have been considered to present
      a globally favorable benefit/risk ratio. However, it is important that in routine
      practice, initiation of anti-TNF-alpha therapy be carefully discussed with the
      patient, extensively explaining the potential benefits and risks of such
      treatment. Prior to starting anti-TNF-alpha therapy, the patients need to be
      screened for latent tuberculosis, hepatitis B virus infection, and (usually)
      hepatitis C virus and HIV infection. Vaccination schedules of IBD patients should
      be evaluated and updated prior to the commencement of anti-TNF-alpha therapy.
      Ordinarily, immunization in adult patients with IBD should not deviate from
      recommended guidelines for the general population. With the exception of live
      vaccines, immunizations can be safely administered in patients with IBD, even
      those on immunosuppressants or biologics. The purpose of this review is providing
      an overview of appropriate steps to prepare patients with IBD for anti-TNF-alpha
      therapy.

PMID- 24667277
TI  - Measurement and simulation of neutron beam fluence energy distributions at the
      neutron time-of-flight facility of iThemba Labs.
AB  - A NE213 proton recoil detector using the time-of-flight technique was used to
      measure neutron beam fluence energy distributions at the neutron time-of-flight
      facility of iThemba Labs. A comparison was performed between neutron beam fluence
      energy distributions calculated by the Monte Carlo code MCNPX and that measured
      for neutron beams of energies up to ~64 MeV for the calibration of detectors. The
      results obtained showed good agreement between the calculated and measured
      distributions. 

PMID- 24667276
TI  - Better quality sleep promotes daytime physical activity in patients with chronic
      pain? A multilevel analysis of the within-person relationship.
AB  - BACKGROUND: Promoting physical activity is key to the management of chronic pain,
      but little is understood about the factors facilitating an individual's
      engagement in physical activity on a day-to-day basis. This study examined the
      within-person effect of sleep on next day physical activity in patients with
      chronic pain and insomnia. METHODS: 119 chronic pain patients monitored their
      sleep and physical activity for a week in their usual sleeping and living
      environment. Physical activity was measured using actigraphy to provide a mean
      activity score each hour. Sleep was estimated with actigraphy and an electronic
      diary, providing an objective and subjective index of sleep efficiency (A-SE, SE)
      and a sleep quality rating (SQ). The individual and relative roles of these sleep
      parameters, as well as morning ratings of pain and mood, in predicting subsequent
      physical activity were examined in multilevel models that took into account
      variations in relationships at the 'Day' and 'Participant' levels. RESULTS: Of
      the 5 plausible predictors SQ was the only significant within-person predictor of
      subsequent physical activity, such that nights of higher sleep quality were
      followed by days of more physical activity, from noon to 11 pm. The temporal
      association was not explained by potential confounders such as morning pain, mood
      or effects of the circadian rhythm. CONCLUSIONS: In the absence of interventions,
      chronic pain patients spontaneously engaged in more physical activity following a
      better night of sleep. Improving nighttime sleep may well be a novel avenue for
      promoting daytime physical activity in patients with chronic pain.

PMID- 24667278
TI  - Nutritional recommendations for synchronized swimming.
AB  - The sport of synchronized swimming is unique, because it combines speed, power,
      and endurance with precise synchronized movements and high-risk acrobatic
      maneuvers. Athletes must train and compete while spending a great amount of time
      underwater, upside down, and without the luxury of easily available oxygen. This
      review assesses the scientific evidence with respect to the physiological
      demands, energy expenditure, and body composition in these athletes. The role of
      appropriate energy requirements and guidelines for carbohydrate, protein, fat,
      and micronutrients for elite synchronized swimmers are reviewed. Because of the
      aesthetic nature of the sport, which prioritizes leanness, the risks of energy
      and macronutrient deficiencies are of significant concern. Relative Energy
      Deficiency in Sport and disordered eating/eating disorders are also of concern
      for these female athletes. An approach to the healthy management of body
      composition in synchronized swimming is outlined. Synchronized swimmers should be
      encouraged to consume a well-balanced diet with sufficient energy to meet demands
      and to time the intake of carbohydrate, protein, and fat to optimize performance
      and body composition. Micronutrients of concern for this female athlete
      population include iron, calcium, and vitamin D. This article reviews the
      physiological demands of synchronized swimming and makes nutritional
      recommendations for recovery, training, and competition to help optimize athletic
      performance and to reduce risks for weight-related medical issues that are of
      particular concern for elite synchronized swimmers. 

PMID- 24667279
TI  - Overexpression of Wilms tumor 1 gene as a negative prognostic indicator in acute
      myeloid leukemia.
AB  - Chromosomal aberrations are useful in assessing treatment options and clinical
      outcomes of acute myeloid leukemia (AML) patients. However, 40 ~ 50% of the AML
      patients showed no chromosomal abnormalities, i.e., with normal cytogenetics aka
      the CN-AML patients. Testing of molecular aberrations such as FLT3 or NPM1 can
      help to define clinical outcomes in the CN-AML patients but with various
      successes. Goal of this study was to test the possibility of Wilms' tumor 1 (WT1)
      gene overexpression as an additional molecular biomarker. A total of 103 CN-AML
      patients, among which 28% had overexpressed WT1, were studied over a period of 38
      months. Patient's response to induction chemotherapy as measured by the complete
      remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were
      measured. Our data suggested that WT1 overexpression correlated negatively with
      the CR rate, DFS and OS. Consistent with previous reports, CN-AML patients can be
      divided into three different risk subgroups based on the status of known
      molecular abnormalities, i.e., the favorable (NPM1(mt)/no FLT3(ITD)), the
      unfavorable (FLT3(ITD)) and the intermediate risk subgroups. The WT1
      overexpression significantly reduced the CR, DFS and OS in both the favorable and
      unfavorable groups. As the results, patients with normal WT1 gene expression in
      the favorable risk group showed the best clinical outcomes and all survived with
      complete remission and disease-free survival over the 37 month study period; in
      contrast, patients with WT1 overexpression in the unfavorable risk group
      displayed the worst clinical outcomes. WT1 overexpression by itself is an
      independent and negative indicator for predicting CR rate, DFS and OS of the CN
      AML patients; moreover, it increases the statistical power of predicting the same
      clinical outcomes when it is combined with the NPM1(mt) or the FLT3(ITD)
      genotypes that are the good or poor prognostic markers of CN-AML.

PMID- 24667280
TI  - Scaling of geometric quantum discord close to a topological phase transition.
AB  - Quantum phase transition is one of the most interesting aspects in quantum many
      body systems. Recently, geometric quantum discord has been introduced to
      signature the critical behavior of various quantum systems. However, it is well
      known that topological quantum phase transition can not be described by the
      conventional Landau's symmetry breaking theory, and thus it is unknown that
      whether previous study can be applicable in this case. Here, we study the
      topological quantum phase transition in Kitaev's 1D p-wave spinless quantum wire
      model in terms of its ground state geometric quantum discord. The derivative of
      geometric quantum discord is nonanalytic at the critical point, in both zero
      temperature and finite temperature cases. The scaling behavior and the
      universality are verified numerically. Therefore, our results clearly show that
      all the key ingredients of the topological phase transition can be captured by
      the nearest neighbor and long-range geometric quantum discord. 

PMID- 24667281
TI  - Beta-adrenergic blockade combined with subcutaneous B-type natriuretic peptide: a
      promising approach to reduce ventricular arrhythmia in heart failure?
AB  - AIMS: Clinical studies failed to prove convincingly efficiency of intravenous
      infusion of neseritide during heart failure and evidence suggested a pro
      adrenergic action of B-type natriuretic peptide (BNP). However, subcutaneous BNP
      therapy was recently proposed in heart failure, thus raising new perspectives
      over what was considered as a promising treatment. We tested the efficiency of a
      combination of oral beta1-adrenergic receptor blocker metoprolol and subcutaneous
      BNP infusion in decompensated heart failure. METHODS AND RESULTS: The effects of
      metoprolol or/and BNP were studied on cardiac remodelling, excitation-contraction
      coupling and arrhythmias in an experimental mouse model of ischaemic heart
      failure following postmyocardial infarction. We determined the cellular and
      molecular mechanisms involved in anti-remodelling and antiarrhythmic actions. As
      major findings, the combination was more effective than metoprolol alone in
      reversing cardiac remodelling and preventing ventricular arrhythmia. The
      association of the two molecules improved cardiac function, reduced hypertrophy
      and fibrosis, and corrected the heart rate, sympatho-vagal balance (low
      frequencies/high frequencies) and ECG parameters (P to R wave interval (PR), QRS
      duration, QTc intervals). It also improved altered Ca(2+) cycling by normalising
      Ca(2+)-handling protein levels (S100A1, SERCA2a, RyR2), and prevented pro
      arrhythmogenic Ca(2+) waves derived from abnormal Ca(2+) sparks in ventricular
      cardiomyocytes. Altogether these effects accounted for decreased occurrence of
      ventricular arrhythmias. CONCLUSIONS: Association of subcutaneous BNP and oral
      metoprolol appeared to be more effective than metoprolol alone. Breaking the
      deleterious loop linking BNP and sympathetic overdrive in heart failure could
      unmask the efficiency of BNP against deleterious damages in heart failure and
      bring a new potential approach against lethal arrhythmia during heart failure.

PMID- 24667282
TI  - The Janus face of BNP therapy in chronic heart failure: beneficial effects
      unmasked by beta blockers?

PMID- 24667283
TI  - Temporal dynamics of norovirus GII.4 variants in Brazil between 2004 and 2012.
AB  - Noroviruses (NoVs) are the major cause of acute gastroenteritis outbreaks, and,
      despite a wide genetic diversity, genotype II.4 is the most prevalent strain
      worldwide. Mutations and homologous recombination have been proposed as
      mechanisms driving the epochal evolution of the GII.4, with the emergence of new
      variants in 1-3-year intervals causing global epidemics. There are no data
      reporting the dynamics of GII.4 variants along a specific period in Brazil.
      Therefore, to improve the understanding of the comportment of these variants in
      the country, the aim of this study was to evaluate the circulation of NoV GII.4
      variants during a 9-year period in 3 out of 5 Brazilian regions. A total of 147
      samples were sequenced, and a phylogenetic analysis of subdomain P2 demonstrated
      the circulation of six GII.4 variants, Asia_2003, Hunter_2004, Den Haag_2006b,
      Yerseke_2006a, New Orleans_2009, and Sydney_2012, during this period. The most
      prevalent variant was Den Haag_2006b, circulating in different Brazilian regions
      from 2006 to 2011. A Bayesian coalescent analysis was used to calculate the mean
      evolutionary rate of subdomain P2 as 7.3 * 10(-3) (5.85 * 10(-3) -8.82 * 10(-3))
      subst./site/year. These analyses also demonstrated that clade Den Haag_2006b
      experienced a rapid expansion in 2005 and another in 2008 after a period of
      decay. The evaluation of the temporal dynamics of NoV GII.4 in Brazil revealed a
      similar pattern, with few exceptions, to the worldwide observation. These data
      highlight the importance of surveillance for monitoring the emergence of new
      strains of NoV GII.4 and its impact on cases of acute gastroenteritis.

PMID- 24667285
TI  - The evolving integrated vascular surgery residency curriculum.
AB  - BACKGROUND: Since their introduction several years ago, integrated (0 + 5)
      vascular surgery residency programs are being increasingly developed across the
      country. To date, however, there is no defined "universal" curriculum for these
      programs and each program is responsible for creating its own curriculum. The aim
      of this study was to review the experiences of current 0 + 5 program directors
      (PDs) to determine what factors contributed to the curricular development within
      their institution. METHODS: Semistructured interviews were conducted with 0 + 5
      PDs to explore their experiences with program development, factors influencing
      the latter, and rationale for current curricula. The interview script was loosely
      structured to explore several factors including time of incoming residents' first
      exposure to the vascular surgical service, timing and rationale behind the timing
      of core surgical rotations throughout the 5 year program, educational value of
      nonsurgical rotations, opportunities for leadership and scholarly activity, and
      influence the general surgery program and institutional climate had on curricular
      structure. All interviews were conducted by a single interviewer. All interviews
      were qualitatively analyzed using emergent theme analysis. RESULTS: Twenty-six 0
      + 5 PDs participated in the study. A total of 69% believed establishing
      professional identity early reduces resident attrition and recommend starting
      incoming trainees on vascular surgical services. Sixty-two percent spread core
      surgical rotations over the first 3 years to optimize general surgical exposure
      and most of the programs have eliminated specific rotations, as they were not
      considered valuable to the goals of training. Factors considered most important
      by PDs in curricular development include building on existing institutional
      opportunities (96%), avoiding rotations considered unsuccessful by "experienced"
      programs (92%), and maintaining a good working relationship with general surgery
      (77%). Fifty-eight percent of PDs voiced concern over the lack of standardization
      among the differing programs and most of the PDs agree that some degree of
      programmatic standardization is critical for the continued success of the 0 + 5
      training paradigm. CONCLUSIONS: Qualitative evaluation of PD experiences with the
      development of 0 + 5 vascular surgery residency programs reveals the key factors
      that commonly influence program design. Programs continue to evolve in both
      structure and content as PDs respond to these influences. Learning from the
      collective experience of PDs and some standardization of the curricula may help
      current and future programs avoid common pitfalls in curricular development.

PMID- 24667284
TI  - Common femoral vein reconstruction using internal jugular vein after blast
      injury.
AB  - Common femoral vein traumatic injuries are rare. Surgical management is
      controversial and by nature case specific. In this report, we present an unusual
      case of an isolated common femoral vein injury from a gunshot blast repaired with
      an interposition internal jugular vein bypass. To our knowledge, this is the
      first reported case of an isolated common femoral vein reconstructed in this
      manner. 

PMID- 24667286
TI  - Assessing the impact of copy number variants on miRNA genes in autism by Monte
      Carlo simulation.
AB  - Autism Spectrum Disorders (ASDs) are childhood neurodevelopmental disorders with
      complex genetic origins. Previous studies have investigated the role of de novo
      Copy Number Variants (CNVs) and microRNAs as important but distinct etiological
      factors in ASD. We developed a novel computational procedure to assess the
      potential pathogenic role of microRNA genes overlapping de novo CNVs in ASD
      patients. Here we show that for chromosomes # 1, 2 and 22 the actual number of
      miRNA loci affected by de novo CNVs in patients was found significantly higher
      than that estimated by Monte Carlo simulation of random CNV events. Out of 24
      miRNA genes over-represented in CNVs from these three chromosomes only hsa-mir
      4436b-1 and hsa-mir-4436b-2 have not been detected in CNVs from non-autistic
      subjects as reported in the Database of Genomic Variants. Altogether the results
      reported in this study represent a first step towards a full understanding of how
      a dysregulated expression of the 24 miRNAs genes affect neurodevelopment in
      autism. We also propose that the procedure used in this study can be effectively
      applied to CNVs/miRNA genes association data in other genomic disorders beyond
      autism. 

PMID- 24667287
TI  - Treatment of hereditary autoinflammatory diseases.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances in
      the treatment of the hereditary autoinflammatory diseases, focusing on Familial
      Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic
      syndrome (TRAPS), cryopyrin-associated periodic syndromes (CAPS) and mevalonate
      kinase deficiency (MKD). We discuss recently published studies and their
      implications for current patient care and future clinical research. RECENT
      FINDINGS: Interleukin (IL)-1 blockade is effective in most autoinflammatory
      conditions. Younger patients require a higher dose per kg of body weight. In FMF,
      colchicine remains the treatment of choice. Single daily dosing appears adequate.
      When colchicine fails, IL-1 blockade is effective. In CAPS, the beneficial effect
      of IL-1 blockade is sustained, and side-effects are limited. There is no evidence
      that one IL-1 blocker is superior to the other. In TRAPS and MKD, IL-1 blockade
      appears effective. Some patients have sufficient suppression of inflammatory
      symptoms with NSAIDs or corticosteroids. SUMMARY: Apart from CAPS and FMF,
      therapy of autoinflammatory diseases is based on small and retrospective studies.
      IL-1 blockade appears effective, but larger prospective trials are needed,
      especially in MKD, TRAPS and colchicine-resistant FMF patients. VIDEO ABSTRACT: 

PMID- 24667288
TI  - Editorial: pregnancy and rheumatoid arthritis - do not let the perfect become the
      enemy of the good.

PMID- 24667289
TI  - Considerations in using registry and health plan data for studying pregnancy in
      rheumatic diseases.
AB  - PURPOSE OF REVIEW: The purpose of this review is to critically evaluate the
      strengths and limitations of different data sources for pregnancy-related
      research in patients with rheumatic diseases. We describe challenges in studying
      adverse pregnancy outcomes in the setting of observational research, with a
      particular focus on the studies of maternal drug exposures. RECENT FINDINGS: We
      discuss potential threats to validity in the assessment of exposure and outcomes
      and controlling for confounding; present findings from selected pregnancy-related
      observational studies conducted using data from registries and health plans; and
      highlight future research opportunities for pregnancy research. SUMMARY: Registry
      and health plan data contribute complementary information to each other. Used
      together, linked data sources may allow clinicians, researchers, and patients to
      obtain a more complete understanding of the risk and benefits associated with
      maternal drug exposure and of the risk factors associated with adverse birth
      outcomes in women with rheumatic disease.

PMID- 24667291
TI  - Local translation of TC10 is required for membrane expansion during axon
      outgrowth.
AB  - The surface of developing axons expands in a process mediated by the exocyst
      complex. The spatio-temporal regulation of the exocyst is only partially
      understood. Here we report that stimulated membrane enlargement in dorsal root
      ganglion (DRG) axons is triggered by intra-axonal synthesis of TC10, a small
      GTPase required for exocyst function. Induced membrane expansion and axon
      outgrowth are inhibited after axon-specific knockdown of TC10 mRNA. To determine
      the relationship of intra-axonal TC10 synthesis with the previously described
      stimulus-induced translation of the cytoskeletal regulator Par3, we investigate
      the signalling pathways controlling their local translation in response to NGF.
      Phosphoinositide 3-kinase (PI3K)-dependent activation of the Rheb-mTOR pathway
      triggers the simultaneous local synthesis of TC10 and Par3. These results reveal
      the importance of local translation in the control of membrane dynamics and
      demonstrate that localized, mTOR-dependent protein synthesis triggers the
      simultaneous activation of parallel pathways. 

PMID- 24667292
TI  - GeneSense: a new approach for human gene annotation integrated with protein
      protein interaction networks.
AB  - Virtually all cellular functions involve protein-protein interactions (PPIs). As
      an increasing number of PPIs are identified and vast amount of information
      accumulated, researchers are finding different ways to interrogate the data and
      understand the interactions in context. However, it is widely recognized that a
      significant portion of the data is scattered, redundant, not considered high
      quality, and not readily accessible to researchers in a systematic fashion. In
      addition, it is challenging to identify the optimal protein targets in the
      current PPI networks. The GeneSense server was developed to integrate gene
      annotation and PPI networks in an expandable architecture that incorporates
      selected databases with the aim to assemble, analyze, evaluate and disseminate
      protein-protein association information in a comprehensive and user-friendly
      manner. Three network models including nodenet, leafnet and loopnet are used to
      identify the optimal protein targets in the complex networks. GeneSense is freely
      available at www.biomedsense.org/genesense.php. 

PMID- 24667293
TI  - Rural oncology: overcoming the tyranny of distance for improved cancer care.
AB  - Approximately one third of Australians with cancer live in regional and rural
      areas of the country. They have a lower rate of survival than those in city areas
      because of less availability of diagnostic and treatment services, later
      diagnosis, and lower socioeconomic status. This article explores rural oncology
      and how it allows patients to access specialist services usually available only
      to those situated in major cities. As the remoteness of hospitals increases,
      treatment and support are increasingly provided by less specialized staff. Rural
      oncology services offer patients access to an oncologist in their community. It
      combines research with community care. It puts together a whole team of
      oncologists, general practitioners, nursing and support staff, other allied
      health staff, and patients and their families. The use of technology, enabling
      teleconferencing and videoconferencing, allows contact among all members of a
      patient's care team and the patient. It allows for shared care of the patient
      with the general practitioner during follow-up and results in a reduction in
      hospital visits. This article gives an overview of the rural oncology experience
      in the New England region of Australia and of the future direction of the
      oncology team in this region. This includes community-oriented projects focused
      on improving cancer care for patients of the New England region, including one
      involving the Aboriginal community. 

PMID- 24667294
TI  - Physician perspective on incorporation of oncology patient quality-of-life,
      fatigue, and pain assessment into clinical practice.
AB  - PURPOSE: Patient-reported outcomes (PROs) such as pain, fatigue, and quality of
      life (QOL) are important for morbidity and mortality in patients with cancer.
      Systematic approaches to collect and incorporate PROs into clinical practice are
      still evolving. We set out to determine the impact of PRO assessment on routine
      clinical practice. METHODS: Beginning in July 2010, the symptom assessment
      questionnaire (SAQ) was administered to every patient in a solid tumor oncology
      practice at an academic center. The SAQ measures pain, fatigue, and QOL, each on
      a scale of 0 to 10 points. Results were available to providers before each visit
      in the electronic medical record. Eighteen months after the SAQ was implemented,
      an online survey was sent to 83 oncology care providers regarding the use of the
      SAQ and how it affected their clinical practice, including discussion with
      patients, duration of visits, and work burden. RESULTS: A total of 53% of care
      providers completed the online survey, producing 44 evaluable surveys. Of these,
      86% of care providers reported using information from the SAQ; > 90% of care
      providers indicated the SAQ did not change the length of clinic visits or
      contribute to increased work burden. A majority of care providers felt that the
      SAQ had helped or enhanced their practice. Providers endorsed the SAQ for
      facilitating communication with their patients. CONCLUSION: This study indicates
      that simple single-item measures of pain, fatigue, and QOL can be incorporated
      into oncology clinical practice with positive implications for both patients and
      physicians without increasing duration of visits or work burden.

PMID- 24667295
TI  - The role of macrophage migration inhibitory factor in anesthetic-induced
      myocardial preconditioning.
AB  - INTRODUCTION: Anesthetic-induced preconditioning (AIP) is known to elicit
      cardioprotective effects that are mediated at least in part by activation of the
      kinases AMPK and PKCepsilon as well as by inhibition of JNK. Recent data
      demonstrated that the pleiotropic cytokine macrophage migration inhibitory factor
      (MIF) provides cardioprotection through activation and/or inhibition of kinases
      that are also known to mediate effects of AIP. Therefore, we hypothesized that
      MIF could play a key role in the AIP response. METHODS: Cardiomyocytes were
      isolated from rats and subjected to isoflurane preconditioning (4 h; 1.5 vol. %).
      Subsequently, MIF secretion and alterations in the activation levels of
      protective kinases were compared to a control group that was exposed to ambient
      air conditions. MIF secretion was quantified by ELISA and AIP-induced activation
      of protein kinases was assessed by Western blotting of cardiomyocyte lysates
      after isoflurane treatment. RESULTS: In cardiomyocytes, preconditioning with
      isoflurane resulted in a significantly elevated secretion of MIF that followed a
      biphasic behavior (30 min vs. baseline: p = 0.020; 24 h vs. baseline p = 0.000).
      Moreover, quantitative polymerase chain reaction demonstrated a significant
      increase in MIF mRNA expression 8 h after AIP. Of note, activation of AMPK and
      PKCepsilon coincided with the observed peaks in MIF secretion and differed
      significantly from baseline. CONCLUSIONS: These results suggest that the
      pleiotropic mediator MIF is involved in anesthetic-induced preconditioning of
      cardiomyocytes through stimulation of the protective kinases AMPK and PKCepsilon.

PMID- 24667296
TI  - Searching for the true diet of marine predators: incorporating Bayesian priors
      into stable isotope mixing models.
AB  - Reconstructing the diet of top marine predators is of great significance in
      several key areas of applied ecology, requiring accurate estimation of their true
      diet. However, from conventional stomach content analysis to recent stable
      isotope and DNA analyses, no one method is bias or error free. Here, we evaluated
      the accuracy of recent methods to estimate the actual proportion of a controlled
      diet fed to a top-predator seabird, the Little penguin (Eudyptula minor). We
      combined published DNA data of penguins scats with blood plasma delta(15)N and
      delta(13)C values to reconstruct the diet of individual penguins fed
      experimentally. Mismatch between controlled (true) ingested diet and dietary
      estimates obtained through the separately use of stable isotope and DNA data
      suggested some degree of differences in prey assimilation (stable isotope) and
      digestion rates (DNA analysis). In contrast, combined posterior isotope mixing
      model with DNA Bayesian priors provided the closest match to the true diet. We
      provided the first evidence suggesting that the combined use of these
      complementary techniques may provide better estimates of the actual diet of top
      marine predators- a powerful tool in applied ecology in the search for the true
      consumed diet.

PMID- 24667297
TI  - Optimising end of life care requires an individualised approach.

PMID- 24667298
TI  - Females and males rely on different cortical regions in Raven's Matrices
      reasoning capacity: evidence from a voxel-based morphometry study.
AB  - Raven's Matrices test (RMT) is a non-verbal test designed to assess individuals'
      ability to reason and solve new problems without relying extensively on
      declarative knowledge derived from schooling or previous experience. Despite a
      large number of behavioral studies that demonstrated gender differences in
      Raven's Matrices reasoning ability, no neural evidence supported this difference.
      In this study, voxel-based morphometry (VBM) was used in an attempt to uncover
      the gender-specific neural basis of Raven's Matrices reasoning ability as
      measured by the combined Raven's Matrices test (CRT) in 370 healthy young adults.
      The behavioral results showed no difference between males and females. However,
      the VBM results showed that the relationship between reasoning ability and
      regional gray matter volume (rGMV) differed between sexes. The association
      between CRT scores and rGMV in the dorsolateral prefrontal cortex (associated
      with visuospatial ability) was significantly greater in males than in females,
      whereas the reverse was true for the inferior frontal cortex (relating to verbal
      reasoning ability) and the medial frontal cortex (engaged in information binding)
      where the association was greater in females. These findings suggest that males
      and females use differently structured brains in different ways to achieve
      similar levels of overall Raven's Matrices reasoning ability. 

PMID- 24667299
TI  - Quantifying anatomical shape variations in neurological disorders.
AB  - We develop a multivariate analysis of brain anatomy to identify the relevant
      shape deformation patterns and quantify the shape changes that explain
      corresponding variations in clinical neuropsychological measures. We use kernel
      Partial Least Squares (PLS) and formulate a regression model in the tangent space
      of the manifold of diffeomorphisms characterized by deformation momenta. The
      scalar deformation momenta completely encode the diffeomorphic changes in
      anatomical shape. In this model, the clinical measures are the response
      variables, while the anatomical variability is treated as the independent
      variable. To better understand the "shape-clinical response" relationship, we
      also control for demographic confounders, such as age, gender, and years of
      education in our regression model. We evaluate the proposed methodology on the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) database using baseline
      structural MR imaging data and neuropsychological evaluation test scores. We
      demonstrate the ability of our model to quantify the anatomical deformations in
      units of clinical response. Our results also demonstrate that the proposed method
      is generic and generates reliable shape deformations both in terms of the
      extracted patterns and the amount of shape changes. We found that while the
      hippocampus and amygdala emerge as mainly responsible for changes in test scores
      for global measures of dementia and memory function, they are not a determinant
      factor for executive function. Another critical finding was the appearance of
      thalamus and putamen as most important regions that relate to executive function.
      These resulting anatomical regions were consistent with very high confidence
      irrespective of the size of the population used in the study. This data-driven
      global analysis of brain anatomy was able to reach similar conclusions as other
      studies in Alzheimer's disease based on predefined ROIs, together with the
      identification of other new patterns of deformation. The proposed methodology
      thus holds promise for discovering new patterns of shape changes in the human
      brain that could add to our understanding of disease progression in neurological
      disorders. 

PMID- 24667300
TI  - Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in
      chemotherapy-naive patients with advanced melanoma and low-normal serum lactate
      dehydrogenase: 'The AGENDA trial'.
AB  - In a previous large randomized, open-label study, retrospective subset analysis
      revealed that the addition of the Bcl-2 antisense oligonucleotide oblimersen to
      dacarbazine (Dac) significantly improved overall survival, progression-free
      survival, and the response rate in chemotherapy-naive patients with advanced
      melanoma and normal baseline serum lactate dehydrogenase (LDH) levels. To confirm
      and expand on this observation, we conducted a prospective double-blind, placebo
      controlled study to determine whether oblimersen augmented the efficacy of Dac in
      advanced melanoma patients with low-normal baseline LDH levels. A total of 314
      chemotherapy-naive patients were randomly assigned to receive Dac (1000 mg/m(2))
      preceded by a 5-day continuous intravenous infusion of either oblimersen sodium
      (7 mg/kg/day) or placebo every 21 days for less than eight cycles. Co-primary
      efficacy endpoints were overall survival and progression-free survival. Response
      and progression of the disease were assessed by independent blinded review of
      computed tomography scan images. No difference in overall nor progression-free
      survival was observed between the Dac-oblimersen and Dac-placebo groups. Although
      the overall (17.2 vs. 12.1%) and durable (10.8 vs. 7.6%) response rates
      numerically favored Dac-oblimersen over Dac-placebo, they did not differ
      significantly (P=0.19 and 0.32, respectively). The incidence of hematologic
      adverse events, particularly thrombocytopenia and neutropenia, was higher in the
      Dac-oblimersen group than in the Dac-placebo group. Withdrawals from the study
      because of treatment-related adverse events were low (i.e. <2.5%) in both groups.
      The addition of oblimersen to Dac did not significantly improve overall survival
      nor progression-free survival in patients with advanced melanoma and low-normal
      levels of LDH at baseline.

PMID- 24667301
TI  - Mitral valve replacement in the elderly is associated with low mortality and
      similar survival to the general population.
AB  - BACKGROUND: With the increase in the elderly population, cardiologists and
      surgeons are faced with an increased incidence of mitral regurgitation. Most of
      these patients are denied surgery due to a misconceived perception of ominous
      surgical results. Our objective was to analyze early and late survival in elderly
      patients after mitral valve surgery in a center in which replacement is the
      procedure of choice. MATERIAL AND METHODS: We obtained clinical follow-up of
      patients older than 70 years who underwent first-time isolated replacement from
      January 2000 to January 2012. Observed survival was compared with expected
      survival in the general population of Uruguay. Independent predictors of
      operative mortality and survival were determined. RESULTS: A total of 127
      patients were included. Global operative mortality was 9.4% (1.8% after year 2006
      vs 15.3% before 2006; p<0.05). Surgery performed before 2006, preoperative
      hematocrit and creatinine were independent predictors for operative mortality
      after multivariate analysis. 6-year survival was 70.2% for females (72.4%
      expected survival, p=ns) and 40.1% in males (63.5% expected survival, p<0.05).
      Independent predictors of survival were surgery performed before 2006 (HR=3.2)
      and female sex (HR=0.4). CONCLUSION: Mitral valve replacement is a feasible
      option for elderly patients with mitral valve disease in centers with lack
      expertise in valve repair. Actual surgical results provide low operative
      mortality and similar survival to general the population (mainly in females).

PMID- 24667302
TI  - Rapid and real-time detection of Porcine Sapelovirus by reverse transcription
      loop-mediated isothermal amplification assay.
AB  - The present study describes the development and validation of a one-step, single
      tube, and real-time reverse transcription loop-mediated isothermal amplification
      (RT-LAMP) detecting Porcine Sapelovirus. RT-LAMP characterized by one strand
      displacement reaction with the specific stem-loop structure and Bst DNA
      polymerase could be finished in 60 min under isothermal condition at 63  degrees
      C. RT-LAMP assay showed higher sensitivity with 10(1) copies/MUL than RT-PCR for
      the detection of Sapelovirus. The specificity of RT-LAMP assay was validated by
      the absence of any cross-reaction with other closely related virus in
      Picornaviridae group and other common virus causing porcine diarrhea. 7 positive
      Sapelovirus infection out of 63 fecal samples were identified using RT-LAMP,
      while 5 positive samples were determined by a conventional RT-PCR. A cost
      effective method for Saplovirus detection with high sensitivity and specificity
      was developed and evaluated.

PMID- 24667303
TI  - Single genome amplification of proviral HIV-1 DNA from dried blood spot specimens
      collected during early infant screening programs in Lusaka, Zambia.
AB  - The ability to evaluate individual HIV-1 virions from the quasispecies of
      vertically infected infants was evaluated in a field setting at the Centre for
      Infectious Disease Research in Zambia. Infant heel-prick blood specimens were
      spotted onto dried blood spot (DBS) filter paper cards at government health
      clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA
      detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On
      samples that tested positive by commercial diagnostic assay, amplification of DNA
      was performed using an in-house assay of the 5' and 3' region of the HIV-1
      genome. Additionally, fragments covering 1200 nucleotides within pol (full length
      protease and partial reverse transcriptase) and 1400 nucleotides within env
      (variable 1-variable 5 region) were further analyzed by single genome
      amplification (SGA). In summary, we have demonstrated an in-house assay for
      amplifying the 5' and 3' proviral HIV-1 DNA as well as pol and env proviral DNA
      fragments from DBS cards collected and analyzed entirely in Zambia. In
      conclusion, this study shows the feasibility of utilizing DBS cards to amplify
      the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes. 

PMID- 24667304
TI  - Does movement proficiency impact on exergaming performance?
AB  - There is growing interest in the use of consumer level exergames in movement
      skill acquisition. The purpose of this study was to investigate the relationship
      between movement proficiency and performance in virtual exergaming. Twenty seven
      children, aged 10-15years participated in an experiment completing the Movement
      Assessment Battery for Children 2 (MABC-2) and a series of XBOX360 Kinect Sports
      exergaming tasks. Significant correlations were observed between MABC-2 aiming
      and catching percentile and exergame javelin and target kick, where the more
      proficient movers tended to perform better in the exergame. Statistically
      significant correlations were observed between MABC-2 balance percentile and
      exergaming sprint and target kick performance. In this study children who scored
      better in real life gross motor movement tasks performed better in most related
      exergaming activities. This suggests current exergaming technology has advanced
      to a point where body movement unencumbered by a physical or remote game device
      tether can extract movements resembling real life tasks, translate them into game
      play and reward proficient movers with higher in-game performance. It is possible
      that benefit gained in an exergaming environment by more proficient movers was a
      result of either their more proficient movement, or a greater ability to adapt to
      the exergame. 

PMID- 24667305
TI  - Nutrition considerations for open-water swimming.
AB  - Open-water swimming (OWS) is a rapidly developing discipline. Events of 5-25 km
      are featured at FINA World Championships, and the international circuit includes
      races of 5-88 km. The Olympic OWS event, introduced in 2008, is contested over 10
      km. Differing venues present changing environmental conditions, including water
      and ambient temperatures, humidity, solar radiation, and unpredictable tides.
      Furthermore, the duration of most OWS events (1-6 hr) creates unique
      physiological challenges to thermoregulation, hydration status, and muscle fuel
      stores. Current nutrition recommendations for open-water training and competition
      are either an extension of recommendations from pool swimming or are extrapolated
      from other athletic populations with similar physiological requirements.
      Competition nutrition should focus on optimizing prerace hydration and glycogen
      stores. Although swimmers should rely on self-supplied fuel and fluid sources for
      shorter events, for races of 10 km or greater, fluid and fuel replacement can
      occur from feeding pontoons when tactically appropriate. Over the longer races,
      feeding pontoons should be used to achieve desirable targets of up to 90 g/ hr of
      carbohydrates from multitransportable sources. Exposure to variable water and
      ambient temperatures will play a significant role in determining race nutrition
      strategies. For example, in extreme environments, thermoregulation may be
      assisted by manipulating the temperature of the ingested fluids. Swimmers are
      encouraged to work with nutrition experts to develop effective and efficient
      strategies that enhance performance through appropriate in-competition nutrition.

PMID- 24667307
TI  - A study of the antibacterial activity of L-phenylalanine and L-tyrosine esters in
      relation to their CMCs and their interactions with 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine, DPPC as model membrane.
AB  - Cationic amino acid-based surfactants are known to interact with the lipid
      bilayer of cell membranes resulting in depolarization, lysis and cell death
      through a disruption of the membrane topology. A range of cationic surfactant
      analogues derived from L-Phenylalanine (C1-C20) and L-Tyrosine (C8-C14) esters
      have been synthesized and screened for their antibacterial activity. The esters
      were more active against gram positive than gram negative bacteria. The activity
      increased with increasing chain length, exhibiting a cut-off effect at C12 for
      gram positive and C8/C10 for gram negative bacteria. The cut-off effect for gram
      negative bacteria was observed at a lower alkyl chain length. The CMC was
      correlated with the MIC, inferring that micellar activity contribute to the cut
      off effect in antibacterial activity. The interaction of the cationic surfactants
      with the phospholipid vesicles (1,2-dipalmitoyl-sn-glycero-3-phosphocholine,
      DPPC) in the presence of 1-anilino-8-naphthalene sulfonate (ANS) and 1,6-diphenyl
      1,3,5-hexatriene (DPH) as fluorescence probes showed that an increase in ionic
      interaction causes an increase in antibacterial activity. Increase in hydrophobic
      interaction increases the antibacterial activity only to a certain chain length,
      attributing to the cut-off effect. Therefore, both electrostatic and hydrophobic
      interactions, involving the polar and nonpolar moieties are of paramount
      importance for the bactericidal properties.

PMID- 24667306
TI  - MYPT1 regulates contractility and microtubule acetylation to modulate integrin
      adhesions and matrix assembly.
AB  - Although much is known about how individual cytoskeletal systems contribute to
      physiological processes such as cell migration and branching morphogenesis,
      little is known about how these different systems actively coordinate their
      functions after polymerization. Here we show that both fibroblasts and developing
      glands reciprocally coordinate levels of cellular contractility and microtubule
      acetylation. We find that this balance is achieved by interaction of the myosin
      phosphatase target subunit of myosin phosphatase with either myosin light chain
      or HDAC6, a microtubule deacetylase. This balance of contractility and
      microtubule acetylation controls progression of adhesion maturation by regulating
      surface density of alpha5beta1 integrin and fibronectin. Thus, we propose that a
      homeostatic balance between contractility and microtubule acetylation is mediated
      by myosin phosphatase via controlled activation and deactivation of myosin II and
      HDAC6. This regulates the surface density of alpha5beta1 integrin to modulate
      fibronectin matrix assembly and governs rates of cell migration and branching
      morphogenesis. 

PMID- 24667308
TI  - MicroRNA319 positively regulates cold tolerance by targeting OsPCF6 and OsTCP21
      in rice (Oryza sativa L.).
AB  - The microRNA319 (miR319) family is conserved among diverse plant species. In rice
      (Oryza sativa L.), the miR319 gene family is comprised of two members, Osa
      miR319a and Osa-miR319b. We found that overexpressing Osa-miR319b in rice
      resulted in wider leaf blades and delayed development. Here, we focused on the
      biological function and potential molecular mechanism of the Osa-miR319b gene in
      response to cold stress in rice. The expression of Osa-miR319b was down-regulated
      by cold stress, and the overexpression of Osa-miR319b led to an enhanced
      tolerance to cold stress, as evidenced by higher survival rates and proline
      content. Also, the expression of a handful of cold stress responsive genes, such
      as DREB1A/B/C, DREB2A, TPP1/2, was increased in Osa-miR319b transgenic lines.
      Furthermore, we demonstrated the nuclear localization of the transcription
      factors, OsPCF6 and OsTCP21, which may be Osa-miR319b-targeted genes. We also
      showed that OsPCF6 and OsTCP21 expression was largely induced by cold stress, and
      the degree of induction was obviously repressed in plants overexpressing Osa
      miR319b. As expected, the down-regulation of OsPCF6 and OsTCP21 resulted in
      enhanced tolerance to cold stress, partially by modifying active oxygen
      scavenging. Taken together, our findings suggest that Osa-miR319b plays an
      important role in plant response to cold stress, maybe by targeting OsPCF6 and
      OsTCP21. 

PMID- 24667309
TI  - The child as econometrician: a rational model of preference understanding in
      children.
AB  - Recent work has shown that young children can learn about preferences by
      observing the choices and emotional reactions of other people, but there is no
      unified account of how this learning occurs. We show that a rational model, built
      on ideas from economics and computer science, explains the behavior of children
      in several experiments, and offers new predictions as well. First, we demonstrate
      that when children use statistical information to learn about preferences, their
      inferences match the predictions of a simple econometric model. Next, we show
      that this same model can explain children's ability to learn that other people
      have preferences similar to or different from their own and use that knowledge to
      reason about the desirability of hidden objects. Finally, we use the model to
      explain a developmental shift in preference understanding. 

PMID- 24667310
TI  - British and American prevention guidelines: different committees, same science,
      considerable agreement.

PMID- 24667311
TI  - Prevention of cardiovascular disease: new guidelines, new tools, but challenges
      remain.

PMID- 24667312
TI  - Anaerobic organic acid metabolism of Candida zemplinina in comparison with
      Saccharomyces wine yeasts.
AB  - Organic acid production under oxygen-limited conditions has been thoroughly
      studied in the Saccharomyces species, but practically never investigated in
      Candida zemplinina, which seems to be an acidogenic species under oxidative
      laboratory conditions. In this study, several strains of C. zemplinina were
      tested for organic acid metabolism, in comparison with Saccharomyces cerevisiae,
      Saccharomyces uvarum and Candida stellata, under fermentative conditions. Only C.
      stellata produced significantly higher acidity in simple minimal media (SM) with
      low sugar content and two different nitrogen sources (ammonia or glutamic acid)
      at low level. However, the acid profile differed largely between the
      Saccharomyces and Candida species and showed inverse types of N-dependence in
      some cases. Succinic acid production was strongly enhanced on glutamic acid in
      Saccharomyces species, but not in Candida species. 2-oxoglutarate production was
      strongly supported on ammonium nitrogen in Candida species, but remained low in
      Saccharomyces. Candida species, C. stellata in particular, produced more pyruvic
      acid regardless of N-sources. From the results, we concluded that the anaerobic
      organic acid metabolisms of C. zemplinina and C. stellata are different from each
      other and also from that of the Saccharomyces species. In the formation of
      succinic acid, the oxidative pathway from glutamic acid seems to play little or
      no role in C. zemplinina. The reductive branch of the TCA cycle, however,
      produces acidic intermediates (malic, fumaric, and succinic acid) in a level
      comparable with the production of the Saccharomyces species. An unidentified
      organic acid, which was produced on glutamic acid only by the Candida species,
      needs further investigation. 

PMID- 24667313
TI  - Active polymers containing Lactobacillus curvatus CRL705 bacteriocins:
      effectiveness assessment in Wieners.
AB  - Bacteriocins from lactic acid bacteria have potential as natural food
      preservatives. In this study two active (synthetic and gluten) films were
      obtained by the incorporation of lactocin 705 and lactocin AL705, bacteriocins
      produced by Lactobacillus curvatus CRL705 with antimicrobial activity against
      spoilage lactic acid bacteria and Listeria. Antimicrobial film effectiveness was
      determined in Wieners inoculated with Lactobacillus plantarum CRL691 and Listeria
      innocua 7 (10(4)CFU/g) stored at 5 degrees C during 45days. Active and control
      (absence of bacteriocins) packages were prepared and bacterial counts in
      selective media were carried out. Visual inspection and pH measurement of Wieners
      were also performed. Typical growth of both inoculated microorganisms was
      observed in control packages which reached 10(6)-10(7)CFU/g at the end of storage
      period. In the active packages, L. innocua 7 was effectively inhibited (2.5 log
      cycles reduction at day 45), while L. plantarum CRL691 was only slightly
      inhibited (0.5 log cycles) up to the second week of storage, then counts around
      10(6)-10(7)CFU/g were reached. Changes in pH values from 6.3 to 5.8 were produced
      and gas formation was observed in active and control packages. The low inhibitory
      effectiveness against lactic acid bacteria is in correlation with the low
      activity observed for lactocin 705 in the presence of fat; Wieners fat content
      (20-30%) may adversely affect antimicrobial activity. This study supports the
      feasibility of using polymers activated with L. curvatus CRL705 bacteriocins to
      control Listeria on the surface of Wieners and highlights the importance of
      evaluating antimicrobial packaging systems for each particular food application. 

PMID- 24667314
TI  - Fungi and mycotoxins in cocoa: from farm to chocolate.
AB  - Cocoa is an important crop, as it is the raw material from which chocolate is
      manufactured. It is grown mainly in West Africa although significant quantities
      also come from Asia and Central and South America. Primary processing is carried
      out on the farm, and the flavour of chocolate starts to develop at that time.
      Freshly harvested pods are opened, the beans, piled in heaps or wooden boxes, are
      fermented naturally by yeasts and bacteria, then dried in the sun on wooden
      platforms or sometimes on cement or on the ground, where a gradual reduction in
      moisture content inhibits microbial growth. Beans are then bagged and marketed.
      In processing plants, the dried fermented beans are roasted, shelled and ground,
      then two distinct processes are used, to produce powdered cocoa or chocolate.
      Filamentous fungi may contaminate many stages in cocoa processing, and poor
      practices may have a strong influence on the quality of the beans. Apart from
      causing spoilage, filamentous fungi may also produce aflatoxins and ochratoxin A.
      This review deals with the growth of fungal species and formation of mycotoxins
      during the various steps in cocoa processing, as well as reduction of these
      contaminants by good processing practices. Methodologies for fungal and mycotoxin
      detection and quantification are discussed while current data about dietary
      exposure and regulation are also presented. 

PMID- 24667315
TI  - Acid stress management by Cronobacter sakazakii.
AB  - Cronobacter sakazakii is a foodborne pathogenic microorganism associated with
      sporadic cases of neonatal meningitis, necrotising enterocolitis, septicaemia,
      bloody diarrhoea and brain abscesses acquired through the consumption of
      contaminated powdered infant formula (PIF). This study aimed to investigate the
      growth of C. sakazakii DPC6529, a particularly stress tolerant clinical isolate,
      in acidified laboratory media and PIF. The possibility of a stationary-phase acid
      tolerance response (ATR) was also investigated. C. sakazakii DPC6529 grew in LB
      broth acidified to pH4.2 with hydrochloric acid (HCl) and was capable of
      relatively fast growth in PIF acidified to pH5.0 with HCl, representing the
      stomach pH reported for newborns and infants. Moreover, bacterial growth in LB
      broth supplemented with 1% (w/v) glucose gave rise to a stationary-phase ATR
      which resulted in enhanced survival against a subsequent acid challenge at pH3.0.
      A transposon mutagenesis approach was used to shed light on some of the molecular
      mechanisms involved in the response C. sakazakii DPC6529 to normally lethal acid
      exposures. The data suggests that repairing damage in proteins and nucleic acids,
      posttranscriptional modification of tRNA molecules and maintenance of the
      integrity of the cellular envelope are key processes in the defence against acid
      stress. Clones carrying transposon insertions in genes encoding the envelope
      stress response regulators CpxR and OmpR were identified as acid-sensitive
      mutants. Further analyses of the ompR defective mutant and its complemented
      counterpart evidenced that OmpR is a key player in the response of C. sakazakii
      to acid stress, although it was not essential to mount an active stationary-phase
      ATR, at least under the tested conditions. The ability of C. sakazakii DPC6529 to
      grow in acid environments and to develop an adaptive stationary-phase ATR may
      allow for its survival or even proliferation within the infant gastrointestinal
      tract after consumption of contaminated milk formulae. 

PMID- 24667316
TI  - Genetic diversity and antibiotic resistance profiles of Campylobacter jejuni
      isolates from poultry and humans in Turkey.
AB  - In this study, the investigation of clonal relations between human and poultry
      Campylobacter jejuni isolates and the determination of susceptibilities of
      isolates to various antibiotics were aimed. A total of 200 C. jejuni isolates
      concurrently obtained from 100 chicken carcasses and 100 humans were genotyped by
      the Pulsed-Field Gel Electrophoresis (PFGE) and automated Repetitive Extragenic
      Palindromic PCR (Rep-PCR, DiversiLab system) methods and were tested for their
      susceptibility to six antibiotics with disk diffusion method. The minimum
      inhibitory concentration (MIC) values of ciprofloxacin (CI), enrofloxacin (EF)
      and erythromycin (EM) were evaluated by E-test. By using PFGE 174 of (87.0%) the
      isolates were able to be typed. The clonally related strains were placed in 35
      different clusters and 115 different genotypes were obtained. All of the two
      hundred isolates could be typed by using Rep-PCR and were divided into 133
      different genotypes. One hundred and fourteen clonally related isolates (57.0%)
      were included in 47 clusters. In disk diffusion test, while the susceptibility
      rates of AMC and S to human and chicken derived C. jejuni isolates were 84.0%
      96.0% and 96.0%-98.0%, respectively, all isolates were susceptible to gentamicin.
      The resistance rates of human isolates to AMP, NA and TE were detected as 44.0%,
      84.0% and 38.0% of the resistances of chicken isolates to these antibiotics were
      34.0%, 95.0% and 56.0%, respectively. The MIC values of human and chicken
      isolates to CI, EF and EM were detected as 81.0-93.0%, 85.0-88.0% and 6.0-7.0%,
      respectively. The clonal proximity rates were detected between human and poultry
      origin C. jejuni isolates. The discriminatory power of PFGE and Rep-PCR was
      similar, with Simpson's diversity indexes of 0.993 and 0.995, respectively.
      Concordance of the two methods as determined by Adjusted Rand coefficient was
      0.198 which showed the low congruence between Rep-PCR and PFGE. High rates of
      quinolone resistance were detected in C. jejuni isolates. This study demonstrated
      that chicken meat played an important role for infections caused by C. jejuni in
      Turkey and erythromycin, amoxicillin clavulanic acid and gentamicin are
      recommended for the treatment of Campylobacteriosis in humans. 

PMID- 24667317
TI  - Acidification of apple and orange hosts by Penicillium digitatum and Penicillium
      expansum.
AB  - New information about virulence mechanisms of Penicillium digitatum and
      Penicillium expansum could be an important avenue to control fungal diseases. In
      this study, the ability of P. digitatum and P. expansum to enhance their
      virulence by locally modulating the pH of oranges and apples was evaluated. For
      each host, pH changes with a compatible pathogen and a non-host pathogen were
      recorded, and the levels of different organic acids were evaluated to establish
      possible relationships with host pH modifications. Moreover, fruits were
      harvested at three maturity stages to determine whether fruit maturity could
      affect the pathogens' virulence. The pH of oranges and apples decreased when the
      compatible pathogens (P. digitatum and P. expansum, respectively) decayed the
      fruit. The main organic acid detected in P. digitatum-decayed oranges was
      galacturonic acid produced as a consequence of host maceration in the rot
      development process. However, the obtained results showed that this acid was not
      responsible for the pH decrease in decayed orange tissue. The mixture of malic
      and citric acids could at least contribute to the acidification of P. digitatum
      decayed oranges. The pH decrease in P. expansum decayed apples is related to the
      accumulation of gluconic and fumaric acids. The pH of oranges and apples was not
      affected when the non-host pathogen was not able to macerate the tissues.
      However, different organic acid contents were detected in comparison to healthy
      tissues. The main organic acids detected in P. expansum-oranges were oxalic and
      gluconic and in P. digitatum-apples were citric, gluconic and galacturonic.
      Further research is needed to identify the pathogenicity factors of both fungi
      because the contribution of organic acids has profound implications. 

PMID- 24667318
TI  - Kefir fermented milk and kefiran promote growth of Bifidobacterium bifidum
      PRL2010 and modulate its gene expression.
AB  - Bifidobacteria constitute one of the dominant groups of microorganisms colonizing
      the human gut of infants. Their ability to utilize various host-derived glycans
      as well as dietary carbohydrates has received considerable scientific attention.
      However, very little is known about the role of fermented foods, such as kefir,
      or their constituent glycans, such as kefiran, as substrates for bifidobacterial
      growth and for the modulation of the expression of bifidobacterial host-effector
      molecules. Here, we show that Bifidobacterium bifidum PRL2010 exhibits high
      growth performance among the bifidobacterial strains tested when cultivated on
      kefir and/or kefiran polymer. Furthermore, a 16S rRNA metagenomic approach
      revealed that the microbiota of kefir is modified upon the addition of PRL2010
      cells to the kefir matrix. Finally, our results show that kefir and kefiran are
      able to influence the transcriptome of B. bifidum PRL2010 causing increased
      transcription of genes involved in the metabolism of dietary glycans as well as
      genes that act as host-microbe effector molecules such as pili. Altogether, these
      data support the use of kefir as a valuable means for the delivery of effective
      microbial cells in probiotic therapy. 

PMID- 24667319
TI  - Storage of pork meat under modified atmospheres containing vapors from commercial
      alcoholic beverages.
AB  - The present study aimed to evaluate the effect of AB vapors on microbial,
      physicochemical, and sensory profile of pork meat stored in different MAP
      conditions. Pork pieces (10g) and cotton/cellulose absorbent cloths (2*2cm) were
      placed into compartmentalized Petri-dishes in two sections. Aliquots (1mL) of
      water (control), 30% v/v and 40% v/v ethanol, whisky, brandy, tsipouro, raki, and
      ouzo were added separately to the cotton/cellulose absorbent cloths. Each pork
      sample was placed in one compartment and cotton/cellulose absorbent cloths
      supplemented with different ABs were placed in a separate compartment of each
      Petri-dish. Samples were packaged in 40% CO2: 30% O2: 30% N2 and 80% O2: 20% CO2
      and stored at 4 and 10 degrees C. Total viable counts, Pseudomonas sp.,
      Brochothrix thermosphacta, lactic acid bacteria, yeasts and molds, and
      Enterobacteriaceae, were enumerated during storage. Changes in pH, color (L*, a*,
      b*), odor, taste, and overall appearance of pork meat were also evaluated along
      with changes in organic acid levels via HPLC. At 4 degrees C, lactic acid
      bacteria and B. thermosphacta were the dominant organisms under 40% CO2: 30% N2:
      30% O2 and 80% O2: 20% CO2, respectively, while at 10 degrees C, lactic acid
      bacteria dominated in both MAP conditions. All applied ABs were effective
      (p<0.05) against lactic acid bacteria, pseudomonads, and B. thermosphacta. The
      inhibitory effect of ABs was also reflected through lower levels of glucose
      consumption or accumulation of lactic, acetic, succinic, and formic acid compared
      to controls. Moreover, packaged samples in 40% CO2: 30% O2: 30% N2 exhibited a
      significant increase (p<0.05) of acetic acid during storage at 4 degrees C, but
      the concentrations of acetic acid in samples exposed to AB vapors were lower than
      those in controls. Both antimicrobial active MAPs extended the shelf-life of pork
      meat by ca. 2-fold, while samples exposed to alcoholic beverages (especially
      ouzo) under 80% O2: 20% CO2 resulted in better (p<0.05) sensory properties
      compared to the respective samples under 40% CO2: 30% O2: 30% N2. Overall, vapor
      action of ABs in combination with MAP may constitute a promising, antimicrobial
      packaging technology for extending the shelf-life of pork meat. 

PMID- 24667320
TI  - Accurate and economical detection of ALK positive lung adenocarcinoma with
      semiquantitative immunohistochemical screening.
AB  - Right detection of anaplastic lymphoma kinase (ALK) gene rearrangement is pivotal
      to selection of patients with lung adenocarcinoma for ALK-targeted therapy. We
      explored the potential of combination of immunohistochemistry (IHC) screening and
      fluorescence in situ hybridization (FISH) as an affordable practice. We analyzed
      410 unselected lung adenocarcinomas by ALK IHC (D5F3 clone) and FISH. Some
      equivocal cases were further analyzed by RT-PCR. The EGFR mutation was detected
      by pyrosequencing assay. In total 368 cases which got all IHC, FISH, EGFR
      mutation results were eligible for analysis. Cases were evaluated as IHC score 3+
      (n = 26), score 2+ (n = 9), score 1+ (n = 51), and score 0 (n = 282),
      respectively. 23 of 26 IHC 3+ and 5 of 9 IHC 2+ cases were FISH positive, whereas
      3 of 26 IHC 3+, 4 of 9 IHC 2+ and all 333 IHC 1+/0 cases were FISH negative. If
      considering FISH as the standard, the sensitivity and specificity of ALK IHC
      3+/2+ as ALK positive were 100% and 97.9%, respectively. Three IHC 3+ cases
      reported as FISH "negative" were actually ALK positive confirmed by ALK RT-PCR or
      re-detected. Based on the final classify, ALK IHC 3+/2+ was 100% sensitive and
      98.8% specific. However, FISH was 90.3% sensitive and 100% specific. IHC 2+ was
      regarded as equivocal and need to be confirmed by FISH or RT-PCR. In the 368
      cases, 8.4% cases had ALK positive, 52.2% cases had EGFR mutation, and only one
      case had a coexisting. Manually semiquantitative ALK IHC (primary antibody D5F3
      coupled with secondary DAKO Envision system) used as the initial screening
      combined with auxiliary FISH confirmation is a reliable, economical approach to
      identify ALK positive lung adenocarcinoma. The IHC can find some ALK positive
      cases which would be missed by FISH only.

PMID- 24667321
TI  - Genetic variation in the non-coding genome: Involvement of micro-RNAs and long
      non-coding RNAs in disease.
AB  - It has been found that the majority of disease-associated genetic variants
      identified by genome-wide association studies are located outside of protein
      coding regions, where they seem to affect regions that control transcription
      (promoters, enhancers) and non-coding RNAs that also can influence gene
      expression. In this review, we focus on two classes of non-coding RNAs that are
      currently a major focus of interest: micro-RNAs and long non-coding RNAs. We
      describe their biogenesis, suggested mechanism of action, and discuss how these
      non-coding RNAs might be affected by disease-associated genetic alterations. The
      discovery of these alterations has already contributed to a better understanding
      of the etiopathology of human diseases and yielded insight into the function of
      these non-coding RNAs. We also provide an overview of available databases,
      bioinformatics tools, and high-throughput techniques that can be used to study
      the mechanism of action of individual non-coding RNAs. This article is part of a
      Special Issue entitled: From Genome to Function.

PMID- 24667322
TI  - Involvement of IGF-II receptors in the antioxidant and neuroprotective effects of
      IGF-II on adult cortical neuronal cultures.
AB  - Insulin-like growth factor-II (IGF-II) is a naturally occurring peptide that
      exerts known pleiotropic effects ranging from metabolic modulation to cellular
      development, growth and survival. IGF-II triggers its actions by binding to and
      activating IGF (IGF-I and IGF-II) receptors. In this study, we assessed the
      neuroprotective effect of IGF-II on corticosterone-induced oxidative damage in
      adult cortical neuronal cultures and the role of IGF-II receptors in this effect.
      We provide evidence that treatment with IGF-II alleviates the glucocorticoid
      induced toxicity to neuronal cultures, and this neuroprotective effect occurred
      due to a decrease in reactive oxygen species (ROS) production and a return of the
      antioxidant status to normal levels. IGF-II acts via not only the regulation of
      synthesis and/or activity of antioxidant enzymes, especially manganese superoxide
      dismutase, but also the restoration of mitochondrial cytochrome c oxidase
      activity and mitochondrial membrane potential. Although the antioxidant effect of
      IGF-I receptor activation has been widely reported, the involvement of the IGF-II
      receptor in these processes has not been clearly defined. The present report is
      the first evidence describing the involvement of IGF-II receptors in redox
      homeostasis. IGF-II may therefore contribute to the mechanisms of neuroprotection
      by acting as an antioxidant, reducing the neurodegeneration induced by oxidative
      insults. These results open the field to new pharmacological approaches to the
      treatment of diseases involving imbalanced redox homeostasis. In this study, we
      demonstrated that the antioxidant effect of IGF-II is at least partially mediated
      by IGF-II receptors. 

PMID- 24667323
TI  - A novel functional TagSNP Rs7560488 in the DNMT3A1 promoter is associated with
      susceptibility to gastric cancer by modulating promoter activity.
AB  - DNA-methyltransferase (DNMT)-3A which contains DNMT3A1 and DNMT3A2 isoforms have
      been suggested to play a crucial role in carcinogenesis and showed aberrant
      expression in most cancers. Accumulated evidences also indicated that single
      nucleotide polymorphisms (SNP) in DNMT genes were associated with susceptibility
      to different tumors. We hypothesized that genetic variants in DNMT3A1 promoter
      region are associated with gastric cancer risk. We selected the tagSNPs from the
      HapMap database for the Chinese and genotyped in a case-control study to evaluate
      the association with gastric cancer (GC) in a Chinese population. We identified
      that the functional tagSNP rs7560488 T>C associated with a significantly
      increased risk of GC. In vitro functional analysis by luciferase reporter assay
      and EMSA indicated that the tagSNP rs7560488 T>C substantially altered
      transcriptional activity of DNMT3A1 gene via influencing the binding of some
      transcriptional factors, although a definite transcriptional factor remains to be
      established. Compared with TT homozygotes, subjects who were TC heterozygotes and
      CC homozygotes exhibited a reduced expression of DNMT3A1. Furthermore, stratified
      analysis showed that individuals who harbor TC or CC genotypes less than 60 years
      old were more susceptible to GC. Our results suggest that the genetic variations
      in the DNMT3A1 promoter contribute to the susceptibility to GC and also provide
      an insight that tagSNP rs7560488 T>C may be a promising biomarker for predicting
      GC genetic susceptibility and a valuable information in GC pathogenesis. 

PMID- 24667324
TI  - HBx down-regulated Gld2 plays a critical role in HBV-related dysregulation of miR
      122.
AB  - miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic
      gene expression via post-transcription regulation, and it is potentially
      associated with the development of hepatocellular carcinoma. It has been
      confirmed that miR-122 is down-regulated during HBV infection; however, how HBV
      affects miR-122 is still debated. One research provided evidence that HBx could
      reduce the miR-122 transcription level, but the other insisted that HBV had no
      significant effect on miR-122 transcription level but reduce miR-122 level via
      binding and sequestering endogenous miR-122. It is determinate that Gld2 could
      increase the specific miRNA stabilization by monoadenylation which was a post
      transcription regulation. In this study, we aimed to investigate the mechanism of
      HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it.
      According to the results of a microRNA microarray, we found miR-122 was the most
      down-regulated microRNA in HepG2.2.15 compared to HepG2. As revealed by qRT-PCR
      and western blotting analyses, both miR-122 and Gld2 levels were reduced in
      hepatic cell lines with expression of HBV or HBx but not other proteins of HBV,
      and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR
      122 level. What's more, both HBV and HBx have no significant effect on pre-miR
      122 levels. And the dual-luciferase assay implicated that HBx could reduce the
      Gld2 promoter activity but had no significant effect on miR-122 promoter
      activity. In conclusion, HBx is a critical protein derived from HBV, which
      regulates miR-122 via down-regulating Gld2. 

PMID- 24667325
TI  - Transmission of ranavirus between ectothermic vertebrate hosts.
AB  - Transmission is an essential process that contributes to the survival of
      pathogens. Ranaviruses are known to infect different classes of lower vertebrates
      including amphibians, fishes and reptiles. Differences in the likelihood of
      infection among ectothermic vertebrate hosts could explain the successful
      yearlong persistence of ranaviruses in aquatic environments. The goal of this
      study was to determine if transmission of a Frog Virus 3 (FV3)-like ranavirus was
      possible among three species from different ectothermic vertebrate classes:
      Cope's gray treefrog (Hyla chrysoscelis) larvae, mosquito fish (Gambusia
      affinis), and red-eared slider (Trachemys scripta elegans). We housed individuals
      previously exposed to the FV3-like ranavirus with naive (unexposed) individuals
      in containers divided by plastic mesh screen to permit water flow between
      subjects. Our results showed that infected gray treefrog larvae were capable of
      transmitting ranavirus to naive larval conspecifics and turtles (60% and 30%
      infection, respectively), but not to fish. Also, infected turtles and fish
      transmitted ranavirus to 50% and 10% of the naive gray treefrog larvae,
      respectively. Nearly all infected amphibians experienced mortality, whereas
      infected turtles and fish did not die. Our results demonstrate that ranavirus can
      be transmitted through water among ectothermic vertebrate classes, which has not
      been reported previously. Moreover, fish and reptiles might serve as reservoirs
      for ranavirus given their ability to live with subclinical infections.
      Subclinical infections of ranavirus in fish and aquatic turtles could contribute
      to the pathogen's persistence, especially when highly susceptible hosts like
      amphibians are absent as a result of seasonal fluctuations in relative abundance.

PMID- 24667326
TI  - Small non-coding RNAs in streptomycetes.
AB  - Streptomycetes are Gram-positive, GC-rich, soil dwelling bacteria, occurring
      ubiquitary throughout nature. They undergo extensive morphological changes from
      spores to filamentous mycelia and produce a plethora of secondary metabolites.
      Owing to their complex life cycle, streptomycetes require efficient regulatory
      machinery for the control of gene expression. Therefore, they possess a large
      diversity of regulators. Within this review we summarize the current knowledge
      about the importance of small non-coding RNA for the control of gene expression
      in these organisms. 

PMID- 24667327
TI  - Type I TARPs promote dendritic growth of early postnatal neocortical pyramidal
      cells in organotypic cultures.
AB  - The ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate
      receptors (AMPARs) have been implicated in the establishment of dendritic
      architecture. The transmembrane AMPA receptor regulatory proteins (TARPs)
      regulate AMPAR function and trafficking into synaptic membranes. In the current
      study, we employ type I and type II TARPs to modulate expression levels and
      function of endogenous AMPARs and investigate in organotypic cultures (OTCs) of
      rat occipital cortex whether this influences neuronal differentiation. Our
      results show that in early development [5-10 days in vitro (DIV)] only the type I
      TARP gamma-8 promotes pyramidal cell dendritic growth by increasing spontaneous
      calcium amplitude and GluA2/3 expression in soma and dendrites. Later in
      development (10-15 DIV), the type I TARPs gamma-2, gamma-3 and gamma-8 promote
      dendritic growth, whereas gamma-4 reduced dendritic growth. The type II TARPs
      failed to alter dendritic morphology. The TARP-induced dendritic growth was
      restricted to the apical dendrites of pyramidal cells and it did not affect
      interneurons. Moreover, we studied the effects of short hairpin RNA-induced
      knockdown of endogenous gamma-8 and showed a reduction of dendritic complexity
      and amplitudes of spontaneous calcium transients. In addition, the cytoplasmic
      tail (CT) of gamma-8 was required for dendritic growth. Single-cell calcium
      imaging showed that the gamma-8 CT domain increases amplitude but not frequency
      of calcium transients, suggesting a regulatory mechanism involving the gamma-8 CT
      domain in the postsynaptic compartment. Indeed, the effect of gamma-8
      overexpression was reversed by APV, indicating a contribution of NMDA receptors.
      Our results suggest that selected type I TARPs influence activity-dependent
      dendritogenesis of immature pyramidal neurons.

PMID- 24667328
TI  - Cyp26 enzymes are required to balance the cardiac and vascular lineages within
      the anterior lateral plate mesoderm.
AB  - Normal heart development requires appropriate levels of retinoic acid (RA)
      signaling. RA levels in embryos are dampened by Cyp26 enzymes, which metabolize
      RA into easily degraded derivatives. Loss of Cyp26 function in humans is
      associated with numerous developmental syndromes that include cardiovascular
      defects. Although previous studies have shown that Cyp26-deficient vertebrate
      models also have cardiovascular defects, the mechanisms underlying these defects
      are not understood. Here, we found that in zebrafish, two Cyp26 enzymes, Cyp26a1
      and Cyp26c1, are expressed in the anterior lateral plate mesoderm (ALPM) and
      predominantly overlap with vascular progenitors (VPs). Although singular
      knockdown of Cyp26a1 or Cyp26c1 does not overtly affect cardiovascular
      development, double Cyp26a1 and Cyp26c1 (referred to here as Cyp26)-deficient
      embryos have increased atrial cells and reduced cranial vasculature cells.
      Examining the ALPM using lineage tracing indicated that in Cyp26-deficient
      embryos the myocardial progenitor field contains excess atrial progenitors and is
      shifted anteriorly into a region that normally solely gives rise to VPs. Although
      Cyp26 expression partially overlaps with VPs in the ALPM, we found that Cyp26
      enzymes largely act cell non-autonomously to promote appropriate cardiovascular
      development. Our results suggest that localized expression of Cyp26 enzymes cell
      non-autonomously defines the boundaries between the cardiac and VP fields within
      the ALPM through regulating RA levels, which ensures a proper balance of
      myocardial and endothelial lineages. Our study provides novel insight into the
      earliest consequences of Cyp26 deficiency that underlie cardiovascular
      malformations in vertebrate embryos. 

PMID- 24667329
TI  - Degradation of 4-chloro-3-nitrophenol via a novel intermediate, 4
      chlororesorcinol by Pseudomonas sp. JHN.
AB  - A 4-chloro-3-nitrophenol (4C3NP)-mineralizing bacterium, Pseudomonas sp. JHN was
      isolated from a waste water sample collected from a chemically-contaminated area,
      India by an enrichment method. Pseudomonas sp. JHN utilized 4C3NP as a sole
      carbon and energy source and degraded it with the release of stoichiometric
      amounts of chloride and nitrite ions. Gas chromatography and gas chromatography
      mass spectrometry detected 4-chlororesorcinol as a major metabolite of the 4C3NP
      degradation pathway. Inhibition studies using 2,2'-dipyridyl showed that 4
      chlororesorcinol is a terminal aromatic compound in the degradation pathway of
      4C3NP. The activity for 4C3NP-monooxygenase was detected in the crude extracts of
      the 4C3NP-induced JHN cells that confirmed the formation of 4-chlororesorcinol
      from 4C3NP. The capillary assay showed that Pseudomonas sp. JHN exhibited
      chemotaxis toward 4C3NP. The bioremediation capability of Pseudomonas sp. JHN was
      monitored to carry out the microcosm experiments using sterile and non-sterile
      soils spiked with 4C3NP. Strain JHN degraded 4C3NP in sterile and non-sterile
      soil with same degradation rates. This is the first report of (i) bacterial
      degradation and bioremediation of 4C3NP, (ii) formation of 4-chlororesorcinol in
      the degradation pathway of 4C3NP, (iii) bacterial chemotaxis toward 4C3NP. 

PMID- 24667330
TI  - The cyanobacterial clock and metabolism.
AB  - Cyanobacteria possess the simplest known circadian clock, which presents a unique
      opportunity to study how rhythms are generated and how input signals from the
      environment reset the clock time. The kaiABC locus forms the core of the
      oscillator, and the remarkable ability to reconstitute oscillations using
      purified KaiABC proteins has allowed researchers to study mechanism using the
      tools of quantitative biochemistry. Autotrophic cyanobacteria experience major
      shifts in metabolism following a light-dark transition, and recent work suggests
      that input mechanisms that couple the day-night cycle to the clock involve energy
      and redox metabolites acting directly on clock proteins. We offer a summary of
      the current state of knowledge in this system and present a perspective for
      future lines of investigation.

PMID- 24667331
TI  - Boswellia serrata extract attenuates inflammatory mediators and oxidative stress
      in collagen induced arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads to
      destruction of joints. Current treatment modalities for RA either produce
      symptomatic relief (NSAIDs) or modify the disease process (DMARDs). Though
      effective, their use is also limited by their side effects. As a result, the
      interest in alternative, well tolerated anti-inflammatory remedies has re
      emerged. Our aim was to evaluate the antioxidant and antiarthritic activity of
      Boswellia serrata gum resin extract (BSE) in collagen induced arthritis.
      Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA)
      method. BSE was administered at doses of 100 and 200mg/kg body weight once daily
      for 21 days. The effects of treatment in the rats were assessed by biochemical
      (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators
      (IL-1beta, IL-6, TNF-alpha, IL-10, IFN-gamma and PGE2), and histological studies
      in joints. BSE was effective in bringing significant changes on all the
      parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied.
      Oral administration of BSE resulted in significantly reduced levels of
      inflammatory mediators (IL-1beta, IL-6, TNF-alpha, IFN-gamma and PGE2), and
      increased level of IL-10. The protective effects of BSE against RA were also
      evident from the decrease in arthritis scoring and bone histology. The abilities
      to inhibit proinflammatory cytokines and modulation of antioxidant status suggest
      that the protective effect of Boswellia serrata extract on arthritis in rats
      might be mediated via the modulation of immune system. 

PMID- 24667332
TI  - NICE replies to concerns about scanning patients with head injury who are taking
      anticoagulants and antiplatelet drugs.

PMID- 24667335
TI  - Strongly underestimated dispersion energy in cryptophanes and their complexes.
AB  - Cryptophanes, composed of two bowl-shaped cyclotriveratrylene subunits linked by
      three aliphatic linker groups, are prototypal organic host molecules which bind
      reversibly neutral small guest compounds via London forces. The binding constants
      for these complexes are usually measured in tetrachloroethane and are in the
      range of 10(2)-10(3) M(-1). Here we show that tetrachloroethane is--in contrast
      to the scientific consensus--enclosed by the cryptophane-E cavity. By means of
      NMR spectroscopy we show that the binding constant for CHCl3@cryptophane-E is in
      larger solvents two orders of magnitudes higher than the one measured before. Ab
      initio calculations reveal that attractive dispersion energy is responsible for
      high binding constants and for the formation of imploded cryptophanes which seem
      to be more stable than cryptophanes with empty cavities.

PMID- 24667333
TI  - Evaluation of customised lineage-specific sets of MIRU-VNTR loci for genotyping
      Mycobacterium tuberculosis complex isolates in Ghana.
AB  - BACKGROUND: Different combinations of variable number of tandem repeat (VNTR)
      loci have been proposed for genotyping Mycobacterium tuberculosis complex (MTBC).
      Existing VNTR schemes show different discriminatory capacity among the six human
      MTBC lineages. Here, we evaluated the discriminatory power of a "customized
      MIRU12" loci format proposed previously by Comas et al. based on the standard 24
      loci defined by Supply et al. for VNTR-typing of MTBC in Ghana. METHOD: One
      hundred and fifty-eight MTBC isolates classified into Lineage 4 and Lineage 5
      were used to compare a customized lineage-specific panel of 12 MIRU-VNTR loci
      ("customized MIRU-12") to the standard MIRU-15 genotyping scheme. The resolution
      power of each typing method was determined based on the Hunter-Gaston-
      Discriminatory Index (HGDI). A minimal set of customized MIRU-VNTR loci for
      typing Lineages 4 (Euro-American) and 5 (M. africanum West African 1) strains
      from Ghana was defined based on the cumulative HGDI. RESULTS AND CONCLUSION:
      Among the 106 Lineage 4 strains, the customized MIRU-12 identified a total of 104
      distinct genotypes consisting of 2 clusters of 2 isolates each (clustering rate
      1.8%), and 102 unique strains while standard MIRU-15 yielded a total of 105
      different genotypes, including 1 cluster of 2 isolates (clustering rate: 0.9%)
      and 104 singletons. Among, 52 Lineage 5 isolates, customized MIRU-12 genotyping
      defined 51 patterns with 1 cluster of 2 isolates (clustering rate: 0.9%) and 50
      unique strains whereas MIRU-15 classified all 52 strains as unique. Cumulative
      HGDI values for customized MIRU-12 for Lineages 4 and 5 were 0.98 respectively
      whilst that of standard MIRU-15 was 0.99. A union of loci from the customised
      MIRU-12 and standard MIRU-15 revealed a set of customized eight highly
      discriminatory loci: 4052, 2163B, 40, 4165, 2165, 10,16 and 26 with a cumulative
      HGDI of 0.99 for genotyping Lineage 4 and 5 strains from Ghana.

PMID- 24667334
TI  - Evaluation of potential genotoxicity of HIV entry inhibitors derived from natural
      sources.
AB  - AIDS is a global pandemic that has seen the development of novel and effective
      treatments to improve the quality of life of those infected and reduction of
      spread of the disease. Palmitic Acid (PA), which we identified and isolated from
      Sargassum fusiforme, is a naturally occurring fatty acid that specifically
      inhibits HIV entry by binding to a novel pocket on the CD4 receptor. We also
      identified a structural analogue, 2-bromopalmitate (2-BP), as a more effective
      HIV entry inhibitor with a 20-fold increase in efficacy. We have used the
      structure-activity relationship (SAR) of 2-BP as a platform to identify new small
      chemical molecules that fit into the various identified active sites in an effort
      to identify more potent CD4 entry inhibitors. To validate further drug
      development, we tested the PA and 2-BP scaffold molecules for genotoxic
      potential. The FDA and International Conference on Harmonisation (ICH) recommends
      using a standardized 3-test battery for testing compound genotoxicity consisting
      of the bacterial reverse mutation assay, mouse lymphoma assay, and rat
      micronucleus assay. PA and 2-BP and their metabolites tested negative in all
      three genotoxicty tests. 2-BP is the first derivative of PA to undergo pre
      clinical screening, which will enable us to now test multiple simultaneous small
      chemical structures based on activity in scaffold modeling across the dimension
      of pre-clinical testing to enable transition to human testing. 

PMID- 24667336
TI  - Molecular basis of the association of H208Y and thymidine analogue resistance
      mutations M41L, L210W and T215Y in the HIV-1 reverse transcriptase of treated
      patients.
AB  - Thymidine analogue resistance mutations (TAMs) in HIV-1 reverse transcriptase
      (RT) associate in two clusters: (i) TAM1 (M41L, L210W and T215Y) and TAM2 (D67N,
      K70R, K219E/Q, and sometimes T215F). The amino acid substitution H208Y shows
      increased prevalence in patients treated with nucleoside analogues and is
      frequently associated with TAM1 mutations. We studied the molecular mechanism
      favoring the selection of H208Y in the presence of zidovudine, tenofovir and
      other nucleoside RT inhibitors (NRTIs). NRTI susceptibility was not affected by
      the addition of H208Y in phenotypic assays carried out in MT-4 cells using
      recombinant HIV-1 containing wild-type (subtype B, BH10), H208Y, M41L/L210W/T215Y
      or M41L/H208Y/L210W/T215Y RTs. However, enzymatic studies carried out with
      purified RTs revealed that in the presence of M41L/L210W/T215Y, H208Y increases
      the RT's ability to unblock and extend primers terminated with zidovudine,
      tenofovir and in a lesser extent, stavudine. These effects were observed with
      DNA/DNA complexes (but not with RNA/DNA) and resulted from the higher ATP
      dependent excision activity of the M41L/H208Y/L210W/T215Y RT compared with the
      M41L/L210W/T215Y mutant. The increased rescue efficiency of the
      M41L/H208Y/L210W/T215Y RT was observed in the presence of ATP but not with GTP or
      ITP. Molecular dynamics studies predict an alteration of the stacking
      interactions between Tyr(215) and the adenine ring of ATP due to long-distance
      effects caused by tighter packaging of Tyr(208) and Trp(212). These studies
      provide a mechanistic explanation for the association of TAM-1 and H208Y
      mutations in viral isolates from patients treated with NRTIs. 

PMID- 24667339
TI  - Right mini-parasternotomy may be a good minimally invasive alternative to full
      sternotomy for cardiac valve operations-a propensity-adjusted analysis.
AB  - AIM: Limited realworld data existed for miniparasternotomy approach with good
      sample size in Asian cohorts and most previous studies were eclipsed by case
      heterogeneity. The goal of this study was to compare safety and quality outcomes
      of cardiac noncoronary valve operations by miniparasternotomy and full sternotomy
      approaches on riskadjusted basis. METHODS: From our hospital database, we
      retrieved the cases of non-coronary valve operations from 1 January 2005 to 31
      December 2012, including re-do, emergent, and combined procedures. Estimated
      EuroScore-II and propensity score for choosing mini-parasternotomy were adjusted
      for in the regression models on hospital mortality, complications (pneumonia,
      stroke, sepsis, etc.), and quality parameters (length of stay, ICU time,
      ventilator time, etc.). Non-complicated cases, defined as survival to discharge,
      ventilator use not over one week, and intensive care unit stay not over two
      weeks, were used for quality parameters. RESULTS: There were 283
      miniparasternotomy and 177 full sternotomy cases. EuroScore-II differed
      significantly (medians 2.1 vs. 4.7, p<0.001). Propensity scores for choosing
      miniparasternotomy were higher with lower EuroScore-II (OR=0.91 per 1%, p<0.001),
      aortic regurgitation (OR=2.3, p=0.005), and aortic non-mitral valve disease
      (OR=3.9, p<0.001). Adjusted for propensity score and EuroScore-II, mini
      parasternotomy group had less pneumonia (OR=0.32, p=0.043), less sepsis (OR=0.31,
      p=0.045), and shorter non-complicated length of stay (coefficient=7.2 (day),
      p<0.001) than full sternotomy group, whereas Kaplan-Meier survival, non
      complicated ICU time, non-complicated ventilator time, and 30-day mortality did
      not differ significantly. CONCLUSION: The propensity-adjusted analysis
      demonstrated encouraging safety and quality outcomes for mini-parasternotomy
      valve operation in carefully selected patients.

PMID- 24667337
TI  - Mortality from Alzheimer's disease, Parkinson's disease, and dementias in France
      and Italy: a comparison using the multiple cause-of-death approach.
AB  - OBJECTIVE: We perform an in-depth analysis of all death certificates collected in
      France and Italy with an entry of Parkinson's disease (PD), Alzheimer's disease
      (AD), or another dementia. METHOD: Data are for 2008. We measure how frequently
      these conditions are the underlying cause of death. We then examine what other
      causes are reported on the certificates. RESULTS: In both countries, AD is the
      underlying cause for about 6 in 10 certificates with an AD entry. The proportion
      is lower for PD and dementia, but higher in France than in Italy. Many
      contributing causes reflect the circumstances surrounding the end of life in AD,
      PD, and dementia, often characterized by bed confinement and frailty. DISCUSSION:
      Our research highlights several consequences of the conditions under study that
      could be targeted by public health policy. It also speaks to the existence of
      differences in diagnosis/certification practices that may explain differences in
      mortality levels.

PMID- 24667341
TI  - Double tract vein graft of the lower limb: its efficacy as a conduit for tibial
      bypass.

PMID- 24667342
TI  - Dietary supplement usage, motivation, and education in young, Canadian athletes.
AB  - PURPOSE: To evaluate dietary supplement use in young Canadian athletes, their
      motivation for consuming supplements, and their sources of information. METHODS:
      A questionnaire tested for content validity and reliability was administered to
      567 athletes between the ages of 11 and 25 years from the Canadian athletic
      community in face-to-face meetings. Demographics and sport variables were
      analyzed using descriptive statistics. Fisher's exact tests were used to examine
      dietary supplementation patterns and sources of information regarding dietary
      supplement use between categories of gender, age, sport type, and competition
      level. RESULTS: Ninety-eight percent of athletes were taking at least one dietary
      supplement. Males were more likely to consume protein powder, energy drinks,
      recovery drinks, branched chain amino acids, beta-alanine, and glutamine (p <
      .01); supplements typically associated with increased muscle mass. Athletes 11-17
      years old focused on vitamin and mineral supplements; whereas, athletes 18-25
      years old focused on purported ergogenic supplements. Strength training athletes
      were more likely to consume creatine, glutamine, and protein powders (p < .02).
      Reasons for supplement use included to stay healthy, increase energy, immune
      system, recovery, and overall performance. Primary sources of information were
      family and friends, coaches, and athletic trainers; with 48% of athletes having
      met with a dietitian. Preferred means of education included individual
      consultations, presentations, and the internet. CONCLUSIONS: The majority of
      young athletes are using dietary supplements with the belief they will improve
      performance and health; however, may not always have reliable information.
      Educational programs using individual consultations and electronic media are
      recommended for this demographic.

PMID- 24667340
TI  - Proximal aortic neck angle does not affect early and late EVAR outcomes: an
      AnacondaTM Italian Registry analysis.
AB  - AIM: The aim of this paper was to evaluate early and 3-year results of the
      endovascular repair (EVAR) for abdominal aortic aneurysm (AAA) using the
      AnacondaTM endograft in patients with severe proximal aortic neck angle. METHODS:
      A retrospective analysis of the AnacondaTM Italian Registry was carried out. Two
      groups of patients were identified according to the presence of a severe (Group
      A, GA: >= 60 degrees ) or an absent (Group B, GB: <45 degrees ) proximal aortic
      neck angle. Preoperative, procedural and follow-up data were evaluated.
      Mortality, proximal type I endoleak, freedom from iliac leg thrombosis and
      conversion to open repair were analyzed at 30-day and 3-year follow-up. The
      results of GA and GB were compared. RESULTS: From 2005 to 2012, 1030 patients
      were enrolled in the Registry. Sixty-five patients (6.3%) were included in GA and
      737 (71.5%) in GB. The mean age and AAA diameter were respectively 76.8 years and
      62.7 mm in GA and 77.2 years and 56.5 mm in GB (P=NS). The ASA >= 3 was reported
      in the 95.3% of GA vs. 81% of GB (P=0.005). The endograft main-body was
      repositioned in 35% of cases in GA and 20.7% in GB (P=0.008); there were no
      differences in the main-body ballooning and proximal aortic cuff placement. There
      were no statistical differences in 30-day mortality (GA 1.5% vs. GB 1.3%),
      proximal type I endoleaks (GA 1.5% vs. GB 0.8%), iliac leg thrombosis (GA 1.5%
      vs. GB 1.4%) and conversion to open repair (GA 3% vs. GB 0.6%). The 3-year
      survival was 95.4% in GA and 94.7% in GB (P=NS). Freedom from proximal type I
      endoleak, iliac leg thrombosis and conversion to open repair were respectively
      98.5%, 95.4%, and 95.4% in GA and 97.8%, 96.9%, and 98.5% in GB (P=NS).
      CONCLUSION: The AnacondaTM Italian Registry reports good results in terms of
      clinical success at 3-year follow-up. AAA with severe proximal aortic neck can be
      treated with similar outcomes to AAA with favorable neck anatomy. The endograft
      repositionability is a benefit in cases with severe neck angle.

PMID- 24667343
TI  - Validity of electronically administered Recent Physical Activity Questionnaire
      (RPAQ) in ten European countries.
AB  - OBJECTIVE: To examine the validity of the Recent Physical Activity Questionnaire
      (RPAQ) which assesses physical activity (PA) in 4 domains (leisure, work,
      commuting, home) during past month. METHODS: 580 men and 1343 women from 10
      European countries attended 2 visits at which PA energy expenditure (PAEE), time
      at moderate-to-vigorous PA (MVPA) and sedentary time were measured using
      individually-calibrated combined heart-rate and movement sensing. At the second
      visit, RPAQ was administered electronically. Validity was assessed using
      agreement analysis. RESULTS: RPAQ significantly underestimated PAEE in women
      [median(IQR): 34.9 (22.3, 52.8) vs. 40.6 (32.4, 50.9) kJ/kg/day, 95%LoA: -44.4,
      66.1 kJ/kg/day) and overestimated PAEE in men [45.9 (30.6, 71.1) vs. 45.5 (34.1,
      57.6) kJ/kg/day, 95%LoA: -44.8, 102.6 kJ/kg/day]. Using individualised definition
      of 1MET, RPAQ significantly underestimated MVPA in women [median(IQR): 63.7
      (30.5, 126.9) vs. 73.6 (47.8, 107.2) min/day, 95%LoA: -127.4, 311.9 min/day] and
      overestimated MVPA in men [90.0 (42.3, 188.6) vs. 83.3 (55.1, 125.0) min/day,
      95%LoA: -134.8, 427.3 min/day]. Correlations (95%CI) between subjective and
      objective estimates were statistically significant [PAEE: women, rho = 0.20 (0.15
      0.26); men, rho = 0.37 (0.30-0.44); MVPA: women, rho = 0.18 (0.13-0.24); men, rho
      = 0.31 (0.24-0.38)]. When using non-individualised definition of 1MET (3.5
      mlO2/kg/min), MVPA was substantially overestimated (16 min/day, and 32 min/day in
      women and men, respectively). Revisiting occupational intensity assumptions in
      questionnaire estimation algorithms with occupational group-level empirical
      distributions reduced median PAEE-bias in manual (38.8 kJ/kg/day vs. 6.8
      kJ/kg/day, p<0.001) and heavy manual workers (63.6 vs. -2.8 kJ/kg/day, p<0.001)
      in an independent hold-out sample [corrected]. CONCLUSION: Relative validity of
      RPAQ-derived PAEE and MVPA is comparable to previous studies but underestimation
      of PAEE is smaller. Electronic RPAQ may be used in large-scale epidemiological
      studies including surveys, providing information on all domains of PA.

PMID- 24667345
TI  - Extreme violation of local realism with a hyper-entangled four-photon-eight-qubit
      Greenberger-Horne-Zelinger state.
AB  - The highest qubit Ardehali inequality violation with 203 standard deviations is
      first experimentally demonstrated using the hyper-entangled four-photon-eight
      qubit Greenberger-Horne-Zeilinger (GHZ) state. Moreover, we experimentally
      investigate the robustness of the Ardehali inequality for the four-, six-, and
      eight-qubit GHZ states in a rotary noisy environment systematically. Our results
      first validate the Ardehali' theoretical statement of relation between violation
      of Ardehali inequality and particle number, and proved that Ardehali inequality
      is more robust against noise in larger number qubit GHZ states, and provided an
      experimental benchmark for us to estimate the safety of quantum channel in the
      noisy environment. 

PMID- 24667344
TI  - GABA and glutamate pathways are spatially and developmentally affected in the
      brain of Mecp2-deficient mice.
AB  - Proper brain functioning requires a fine-tuning between excitatory and inhibitory
      neurotransmission, a balance maintained through the regulation and release of
      glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by
      mutations in the methyl-CpG binding protein 2 (MECP2) gene affecting the
      postnatal brain development. Dysfunctions in the GABAergic and glutamatergic
      systems have been implicated in the neuropathology of RTT and a disruption of the
      balance between excitation and inhibition, together with a perturbation of the
      electrophysiological properties of GABA and glutamate neurons, were reported in
      the brain of the Mecp2-deficient mouse. However, to date, the extent and the
      nature of the GABA/glutamate deficit affecting the Mecp2-deficient mouse brain
      are unclear. In order to better characterize these deficits, we simultaneously
      analyzed the GABA and glutamate levels in Mecp2-deficient mice at 2 different
      ages (P35 and P55) and in several brain areas. We used a multilevel approach
      including the quantification of GABA and glutamate levels, as well as the
      quantification of the mRNA and protein expression levels of key genes involved in
      the GABAergic and glutamatergic pathways. Our results show that Mecp2-deficient
      mice displayed regional- and age-dependent variations in the GABA pathway and, to
      a lesser extent, in the glutamate pathway. The implication of the GABA pathway in
      the RTT neuropathology was further confirmed using an in vivo treatment with a
      GABA reuptake inhibitor that significantly improved the lifespan of Mecp2
      deficient mice. Our results confirm that RTT mouse present a deficit in the
      GABAergic pathway and suggest that GABAergic modulators could be interesting
      therapeutic agents for this severe neurological disorder. 

PMID- 24667346
TI  - RNA synthesis and purification for structural studies.
AB  - RNAs play pivotal roles in the cell, ranging from catalysis (e.g., RNase P),
      acting as adaptor molecule (tRNA) to regulation (e.g., riboswitches). Precise
      understanding of its three-dimensional structures has given unprecedented insight
      into the molecular basis for all of these processes. Nevertheless, structural
      studies on RNA are still limited by the very special nature of this polymer. The
      most common methods for the determination of 3D RNA structures are NMR and X-ray
      crystallography. Both methods have their own set of requirements and give
      different amounts of information about the target RNA. For structural studies,
      the major bottleneck is usually obtaining large amounts of highly pure and
      homogeneously folded RNA. Especially for X-ray crystallography it can be
      necessary to screen a large number of variants to obtain well-ordered single
      crystals. In this mini-review we give an overview about strategies for the
      design, in vitro production, and purification of RNA for structural studies. 

PMID- 24667347
TI  - Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3beta
      related T regulatory cell insufficiency.
AB  - BACKGROUND: Oral administration of bacterial extracts (eg, Broncho-Vaxom (BV))
      has been proposed to attenuate asthma through modulating Treg cells. However, the
      underlying mechanism has not been fully characterized. This study sought to
      assess the effects of oral administration of BV on GSK-3beta expression and Treg
      cells in ovalbumin (OVA)-induced asthmatic mice models. METHOD: Asthmatic mice
      models were established with OVA challenge and treated with oral administration
      of BV. Next, infiltration of inflammatory cells including eosinophil and
      neutrophils, mucous metaplasia, levels of Th1/Th2/Treg-typed cytokines and
      expression of GSK3beta and Foxp3 were examined in asthmatic mice models by
      histological analysis, Bio-Plex and western blot, respectively. Moreover, the
      frequencies of Treg cells were evaluated in cultured splenocytes by flow
      cytometry in the presence of BV or GSK3beta siRNA interference. RESULTS: We found
      significant decrease of infiltrated inflammatory cells in bronchoalveolar lavage
      fluid (BALF) in asthmatic mice models after oral administration of BV. Oral
      administration of BV was shown to significantly suppress mucus metaplasia, Th2
      typed cytokine levels and GSK3beta expression while increasing Foxp3 production
      in asthmatic mice models. Moreover, BV significantly enhanced GSK3beta-related
      expansion of Treg cells in cultured spleen cells in vitro. CONCLUSION: Our
      findings provide evidence that oral administration of BV is capable of
      attenuating airway inflammation in asthmatic mice models, which may be associated
      with GSK3beta-related expansion of Treg cells.

PMID- 24667348
TI  - Life-threatening coagulopathy and hypofibrinogenaemia induced by tigecycline in a
      patient with advanced liver cirrhosis.
AB  - Bacterial infections because of multidrug-resistant (MDR) bacteria are spreading
      worldwide. In patients with advanced liver cirrhosis, healthcare-acquired and
      hospital-acquired infections are common and are frequently sustained by MDR
      bacteria. In these settings, tigecycline, a new antibiotic, has been shown to be
      useful in the treatment of MDR bacteria, and it has been proposed for the
      treatment of hospital-acquired infections in patients with cirrhosis.
      Nevertheless, poor data exist on the safety profile of tigecycline in patients
      with cirrhosis. Here, an experience is reported in a female patient with advanced
      liver cirrhosis, who developed sepsis by an MDR Stenotrophomonas maltophilia and
      was treated with tigecycline. She experienced life-threatening side effects
      consisting of severe coagulopathy with hypofibrinogenaemia and subsequent
      gastrointestinal haemorrhage. The side effect disappeared after the withdrawal of
      tigecycline. Therefore, a strict monitoring of coagulation parameters in patients
      with cirrhosis treated with tigecycline is recommended. 

PMID- 24667349
TI  - Serum alanine aminotransferase predicts interventricular septum thickness and
      left ventricular mass in patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Alanine aminotransferase (ALT) is a marker of nonalcoholic fatty
      liver disease (NAFLD) and predicts type 2 diabetes mellitus (DM2) as well as
      coronary events independently of traditional risk factors and the features of the
      metabolic syndrome. The extent to which interventricular septum thickness (IVS)
      and left ventricular mass (LVM) are associated with ALT levels in cohorts of
      individuals with body weights ranging from overweight to morbid obesity and NAFLD
      remains still unknown. MATERIALS AND METHODS: This was a cross-sectional pilot
      study involving 151 young White participants with liver ultrasound-proven NAFLD.
      Standard echocardiograms were used to define LVM, IVS, and left ventricle
      diastolic function [mitral inflow velocity pattern (E/A ratio) and mitral annulus
      velocity by tissue Doppler imaging (Em/Am ratio)]. Participants were classified
      according to ALT quartiles: p25, p50, p75, and p100. RESULTS: The study included
      36 men and 115 women with an age of 38.4 +/- 0.7 years and BMI of 43.9 +/- 0.6
      kg/m2. p100 participants disclosed significantly higher homeostasis model
      assessment (P=0.003), DM2 (P=0.002), and hypertension (P=0.01) prevalence,
      whereas LVM, IVS, E/A, and Em/Am ratios were significantly higher in this group
      when compared with their p25 peers (P<0.01). IVS's and LVM's variance were
      significantly predicted by the statistical models including ALT independently of
      BMI, hypertension, and DM2. CONCLUSION: ALT levels predict both IVS and LVM in
      NAFLD individuals irrespective of their BMI, DM2, hypertension, age, and sex. ALT
      levels behave as a surrogate marker of left ventricular hypertrophy in overweight
      and/or obese NAFLD patients. Hence, it seems worth obtaining cardiac ultrasounds
      in NAFLD patients with elevated ALT levels.

PMID- 24667350
TI  - Isolation, identification and activities of natural antioxidants from Callicarpa
      kwangtungensis Chun.
AB  - Reactive oxygen species leads to some diseases associated with oxidative stress.
      Callicarpa kwangtungensis Chun (CK) is a common remedy in traditional Chinese
      medicine and possesses diverse biological activities involving antioxidant
      properties; its main compounds phenylethanoid glycosides (PG) and flavonoids are
      always reported as antioxidants. In order to develop CK as a safe and activated
      antioxidant, our investigation was performed to validate antioxidant properties
      and assess which types of compounds (similar polarity or similar structure), even
      which compounds, played the role of antioxidants. The extracted compounds of CK
      were analyzed qualitatively and quantitatively by HPLC-DAD-ESI-Trap MS and UV for
      their contents and antioxidant activities. The correlations between antioxidant
      activities and known contents were respectively counted and a semi-quantitative
      experiment was designed to screen antioxidant compounds of CK with HPLC-UV. The n
      butanol fraction (BF) showed the highest total phenolic and flavonoid contents
      (TPC, TFC), and three PG (forsythiaside B, poliumoside and acteoside) contents.
      BF showed the significantly best (P<0.05) activities in most assays. There were
      significant correlations (P<0.05) between DPPH*, ABTS(+)*, *O2(-) scavenging,
      Cu(2+)-chelating, anti-lipidperoxidation activities and TPC. BF also has
      significant antioxidant activities on CCl4-induced acute liver injury Mice and
      TBHP-reduced HepG2 cells. Nine PG (forsythiaside B, poliumoside, acteoside,
      alyssonoside, brandioside and their derivatives) and one flavone (rhamnazin) were
      screened out as antioxidants. BF in CK contained abundant polyphenolic, which
      reflected some definite antioxidant properties. The antioxidant compounds
      consisted at the least of nine PG and one flavone.

PMID- 24667351
TI  - Effects of high affinity leptin antagonist on prolactin receptor deficient male
      mouse.
AB  - Hyperprolactinemia occurs during gestation and lactation with marked hyperphagia
      associated with leptin resistance. Prolactin (PRL) induces the expression of
      orexigenic neuropeptide Y (NPY) in hypothalamic dorsomedial nucleus (DMH) leading
      to hyperphagia. Along this line prolactin receptor deficient (PRLR-/-) mice are
      resistant to obesity under high fat diet due to increased energy expenditure. As
      these mice have an altered food intake, our objective was to test whether leptin
      is responsible for these characteristics. PRLR-/- male mice and control
      littermates were injected subcutaneously every other day with 12 mg/kg pegylated
      superactive mouse leptin antagonist (PEG-SMLA) for 3 weeks. We tested the effect
      of PEG-SMLA on body weight, food intake and metabolic parameters. The antagonist
      led to a rapid increase in body weight (20%) but increased adipose mass in PEG
      SMLA treated mice was less pronounced in PRLR-/- than in WT mice. Food intake of
      PEG-SMLA-injected animals increased during the first week period of the
      experiment but then declined to a similar level of the control animals during the
      second week. Interestingly, PRLR-/- mice were found to have the same bone volume
      than those of control mice although PEG-SMLA increased bone mass by 7% in both
      strains. In addition, PEG-SMLA led to insulin resistance and glucose intolerance
      as well as an altered lipid profile in treated mice. Altogether, these results
      suggest that PRLR-/- mice respond to leptin antagonist similarly to the control
      mice, indicating no interaction between the actions of the two hormones. 

PMID- 24667352
TI  - Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and
      hospitalization rates among sickle cell patients in Cameroon.
AB  - BACKGROUND: Genetic variation at loci influencing adult levels of HbF have been
      shown to modify the clinical course of sickle cell disease (SCD). Data on this
      important aspect of SCD have not yet been reported from West Africa. We
      investigated the relationship between HbF levels and the relevant genetic loci in
      610 patients with SCD (98% HbSS homozygotes) from Cameroon, and compared the
      results to a well-characterized African-American cohort. METHODS AND FINDINGS:
      Socio-demographic and clinical features were collected and medical records
      reviewed. Only patients >5 years old, who had not received a blood transfusion or
      treatment with hydroxyurea were included. Hemoglobin electrophoresis and a full
      blood count were conducted upon arrival at the hospital. RFLP-PCR was used to
      describe the HBB gene haplotypes. SNaPshot PCR, Capillary electrophoresis and
      cycle sequencing were used for the genotyping of 10 selected SNPs. Genetic
      analysis was performed with PLINK software and statistical models in the
      statistical package R. Allele frequencies of relevant variants at BCL11A were
      similar to those detected in African Americans; although the relationships with
      Hb F were significant (p <.001), they explained substantially less of the
      variance in HbF than was observed among African Americans (~ 2% vs 10%). SNPs in
      HBS1L-MYB region (HMIP) likewise had a significant impact on HbF, however, we did
      not find an association between HbF and the variations in HBB cluster and
      OR51B5/6 locus on chromosome 11p, due in part to the virtual absence of the
      Senegal and Indian Arab haplotypes. We also found evidence that selected SNPs in
      HBS1L-MYB region (HMIP) and BCL11A affect both other hematological indices and
      rates of hospitalization. CONCLUSIONS: This study has confirmed the associations
      of SNPs in BCL11A and HBS1L-MYB and fetal haemoglobin in Cameroonian SCA
      patients; hematological indices and hospitalization rates were also associated
      with specific allelic variants.

PMID- 24667353
TI  - "Permethrin chronic exposure alters motor coordination in rats: effect of calcium
      supplementation and amlodipine".
AB  - Recently was observed that pyrethroids decrease motor coordination and that
      calcium channels can be important targets for this effect. To contribute with
      this observation, this work studied the motor coordination and exploration (using
      hole-board apparatus), and locomotion (using open-field apparatus) of rats
      exposed to following treatments: permethrin (PM), PM plus calcium gluconate (CG)
      and PM plus amlodipine (AML). The results obtained show that CG or AML alone not
      changed the motor coordination while PM decreases it. CG kept the effect of
      permethrin; AML, however, decreased the values of permethrin to the control.
      Locomotor activity and exploration, which could confound results of motor
      coordination, were not modified by treatments. The concentration of PM in brain
      tissue was increased by the CG and AML. The neurosomatic index (weight brain/body
      weight) was increased by the PM and PM+CG. In conclusion, the combined results
      here obtained indicates that the calcium ion and the channels in which it is
      involved can be important targets for the toxic effect of pyrethroid insecticide
      permethrin on motor nerve activity of rats. 

PMID- 24667354
TI  - Differential expression of microRNAs in periurethral vaginal wall tissues of
      postmenopausal women with and without stress urinary incontinence.
AB  - OBJECTIVE: The aims of this study were to investigate microRNA (miRNA) expression
      profiles in the periurethral vaginal wall tissues of postmenopausal women with
      and without stress urinary incontinence (SUI) and to explore the putative target
      genes associated with SUI via miRNA-messenger RNA (mRNA) pair prediction.
      METHODS: Periurethral vaginal wall tissues of postmenopausal women with SUI (n =
      13) and matched continent postmenopausal women (n = 13) were collected during
      transvaginal surgical operation. Total RNAs were extracted and miRNAs were
      profiled by TaqMan Array Human MicroRNA assays in three case-control pairs.
      TargetScanS, PicTar, and miRanda were used to obtain the putative miRNA-mRNA
      pairs based on sequence data, and three pairs were predicated. The relative
      expression levels of miRNAs in predicated miRNA-mRNA pairs were quantified in 10
      other case-control pairs by real-time polymerase chain reaction. The expression
      levels of mRNAs and corresponding proteins were estimated via real-time
      polymerase chain reaction and Western blot analysis. RESULTS: Twelve miRNAs were
      identified to be differentially expressed between two groups: the significantly
      up-regulated let-7a, miR-101#, miR-125b-2#, miR-190b, and miR-892b, and the down
      regulated miR-124, miR-330-3p, miR-485-3p, miR-517b, miR-523, miR-589, and miR
      93#. Moreover, three miRNA-mRNA pairs of interest were established via
      computational algorithms: miR-124 and growth factor receptor-bound protein 2; miR
      330-3p and bicaudal D homolog 2; and miR-93# and signal transducer and activator
      of transcription 3. The expression levels of the three miRNAs were quantified,
      and a reduction in SUI was revealed. On the other hand, increased expression
      levels of predicated mRNAs and their protein products were detected. CONCLUSIONS:
      This study reports the differential expression of 12 miRNAs in SUI and predicates
      three miRNA-mRNA pairs. Interestingly, all three predicated target genes are
      associated with neurodegenerative conditions, indicating the potential
      significance of neurodegenerative mechanisms in the etiology of SUI.

PMID- 24667355
TI  - Ovary and unilateral oophorectomy: is having one the same as having two?

PMID- 24667356
TI  - Hormone therapy and vasomotor symptoms after the Women's Health Initiative.

PMID- 24667357
TI  - An overview of current and emerging SERMs.
AB  - Selective estrogen receptor modulators (SERMs) are compounds that exhibit tissue
      specific estrogen receptor (ER) agonist or antagonist activity, and are used for
      various indications, including treatment of breast cancer, osteoporosis, and
      menopausal symptoms. Endometrial safety has been a key differentiator between
      SERMs in clinical practice. For example, tamoxifen exhibits ER agonist activity
      in the uterus, resulting in an increased risk of endometrial hyperplasia and
      malignancy, whereas raloxifene and bazedoxifene have neutral effects on the
      uterus. Based on their efficacy and long-term safety, SERMs are increasingly
      being prescribed for women who cannot tolerate other treatment options and for
      younger women at an increased risk of fracture who may remain on therapy for long
      periods of time. Continuing advances in the understanding of SERM mechanisms of
      action and structural interactions with the ER may lead to the development of new
      agents and combinations of agents to provide optimal treatments to meet the
      varying needs of postmenopausal women. One such example is the tissue selective
      estrogen complex, which partners a SERM with 1 or more estrogens, with the aim of
      blending the desired estrogen-receptor agonist activities of estrogens on
      vasomotor symptoms, vulvar-vaginal atrophy, and loss of bone mass with the tissue
      selectivity of a SERM. 

PMID- 24667358
TI  - Nutrient transitions are a source of persisters in Escherichia coli biofilms.
AB  - Chronic and recurrent infections have been attributed to persisters in biofilms,
      and despite this importance, the mechanisms of persister formation in biofilms
      remain unclear. The plethora of biofilm characteristics that could give rise to
      persisters, including slower growth, quorum signaling, oxidative stress, and
      nutrient heterogeneity, have complicated efforts to delineate formation pathways
      that generate persisters during biofilm development. Here we sought to
      specifically determine whether nutrient transitions, which are a common metabolic
      stress encountered within surface-attached communities, stimulate persister
      formation in biofilms and if so, to then identify the pathway. To accomplish
      this, we established an experimental methodology where nutrient availability to
      biofilm cells could be controlled exogenously, and then used that method to
      discover that diauxic carbon source transitions stimulated persister formation in
      Escherichia coli biofilms. Previously, we found that carbon source transitions
      stimulate persister formation in planktonic E. coli cultures, through a pathway
      that involved ppGpp and nucleoid-associated proteins, and therefore, tested the
      functionality of that pathway in biofilms. Biofilm persister formation was also
      found to be dependent on ppGpp and nucleoid-associated proteins, but the
      importance of specific proteins and enzymes between biofilm and planktonic
      lifestyles was significantly different. Data presented here support the
      increasingly appreciated role of ppGpp as a central mediator of bacterial
      persistence and demonstrate that nutrient transitions can be a source of
      persisters in biofilms. 

PMID- 24667360
TI  - Dipeptidyl peptidase-4 inhibition by Pterocarpus marsupium and Eugenia jambolana
      ameliorates streptozotocin induced Alzheimer's disease.
AB  - Alzheimer's disease (AD), the most common form of dementia, is characterized by
      the loss of normal functions of brain cells and neuronal death, ultimately
      leading to memory loss. Recent accumulating evidences have demonstrated the
      therapeutic potential of anti-diabetic agents, such as dipeptidyl peptidase-4
      (DPP-4) inhibitors, for the treatment of Alzheimer's disease (AD), providing
      opportunities to explore and test the DPP-4 inhibitors for treating this fatal
      disease. Prior studies determining the efficacy of Pterocarpus marsupium (PM,
      Fabaceae) and Eugenia jambolana (EJ, Myrtaceae) extracts for ameliorating type 2
      diabetes have demonstrated the DPP-4 inhibitory properties indicating the
      possibility of using of these extracts even for the treating AD. Therefore, in
      the present study, the neuroprotective roles of PM and EJ for ameliorating the
      streptozotocin (STZ) induced AD have been tested in rat model. Experimentally, PM
      and EJ extracts, at a dose range of 200 and 400mg/kg, were administered orally to
      STZ induced AD Wistar rats and cognitive evaluation tests were performed using
      radial arm maze and hole-board apparatus. Following 30 days of treatment with the
      extracts, a dose- and time-dependent attenuation of AD pathology, as evidenced by
      decreasing amyloid beta 42, total tau, phosphorylated tau and neuro-inflammation
      with an increase in glucagon-like peptide-1 (GLP-1) levels was observed.
      Therefore, PM and EJ extracts contain cognitive enhancers as well as
      neuroprotective agents against STZ induced AD. 

PMID- 24667359
TI  - Calcineurin/NFAT signaling represses genes Vamp1 and Vamp2 via PMCA-dependent
      mechanism during dopamine secretion by Pheochromocytoma cells.
AB  - BACKGROUND: Plasma membrane Ca(2+)-ATPases (PMCA) extrude Ca(2+) ions out of the
      cell and contribute to generation of calcium oscillations. Calcium signaling is
      crucial for transcriptional regulation of dopamine secretion by neuroendocrine
      PC12 cells. Low resting [Ca(2+)]c in PC12 cells is maintained mainly by two
      Ca(2+)-ATPases, PMCA2 and PMCA3. Recently, we found that Ca(2+) dependent
      phosphatase calcineurin was excessively activated under conditions of
      experimental downregulation of PMCA2 or PMCA3. Thus, the aim of this study was to
      explain if, via modulation of the Ca(2+)/calcineurin-dependent nuclear factor of
      activated T cells (NFAT) pathway, PMCA2 and PMCA3 affect intracellular signaling
      in pheochromocytoma/neuronal cells/PC12 cells. Secondly, we tested whether this
      might influence dopamine secretion by PC12 cells. RESULTS: PMCA2- and PMCA3
      deficient cells displayed profound decrease in dopamine secretion accompanied by
      a permanent increase in [Ca(2+)]c. Reduction in secretion might result from
      changes in NFAT signaling, following altered PMCA pattern. Consequently,
      activation of NFAT1 and NFAT3 transcription factors was observed in PMCA2- or
      PMCA3-deficient cells. Furthermore, chromatin immunoprecipitation assay indicated
      that NFATs could be involved in repression of Vamp genes encoding vesicle
      associated membrane proteins (VAMP). CONCLUSIONS: PMCA2 and PMCA3 are crucial for
      dopamine secretion in PC12 cells. Reduction in PMCA2 or PMCA3 led to calcium
      dependent activation of calcineurin/NFAT signaling and, in consequence, to
      repression of the Vamp gene and deterioration of the SNARE complex formation in
      PC12 cells.

PMID- 24667361
TI  - Glutamatergic neurotransmission in the inferior colliculus influences
      intrastriatal haloperidol-induced catalepsy.
AB  - The inferior colliculus (IC) is an important midbrain relay station for the
      integration of descending and ascending auditory information. In addition, it has
      also been implicated in the processing of acoustic information of aversive
      nature, as well as in sensory-motor gating. There is evidence that glutamate
      mediated mechanisms at the IC level influence haloperidol-induced catalepsy. The
      present study investigated the influence of glutamate-mediated mechanisms in the
      IC on catalepsy induced by intrastriatal microinjection of haloperidol (10
      MUg/0.5 MUl). Male Wistar rats received bilateral intracollicular microinjections
      of the glutamate receptor agonist NMDA (10 or 20 nmol/0.5 MUl), the NMDA receptor
      antagonists MK-801 (15 or 30 nmol/0.5 MUl) or physiological saline (0.5 MUl),
      followed by bilateral microinjections of haloperidol (10 MUg/0.5 MUl) or vehicle
      (0.5 MUl) into the dorso-rostral or ventro-rostral striatum. The catalepsy test
      was performed positioning both forepaws of the rats on an elevated horizontal
      wooden bar and recording the time during which the animal remained in this
      position. The results showed that the administration of physiological saline in
      the IC followed by the microinjection of haloperidol in the dorso-rostral region
      of the striatum was not able to induce catalepsy. However, when the bilateral
      administration of NMDA into the IC was followed by microinjection of haloperidol
      into the dorso-rostral striatum, catalepsy was observed. The microinjection of
      haloperidol into the ventro-rostral striatum induced catalepsy, counteracted by
      previous administration of MK-801 into the IC. These findings suggest that
      glutamate-mediated mechanisms in the IC can influence the intrastriatal
      haloperidol-induced catalepsy and that the IC plays an important role as a
      sensorimotor interface.

PMID- 24667362
TI  - Enrichment and individual housing reinforce the differences in aggressiveness and
      amphetamine response in 129S6/SvEv and C57BL/6 strains.
AB  - As different kinds of enrichment equipment are applied to standard rodent
      laboratory housing conditions in Europe (Directive 2010/63/EU) and worldwide, it
      is essential to understand how it may influence the brain and behaviour of
      animals. We observed common inbred mouse strains 129S6/SvEv/Tac (129) and C57BL/6
      Bkl (B6) reared in 3 different environments: standard housing (SH), individual
      housing (IH) and enriched environment (EE). We measured common behavioural
      parameters, social behaviour and BDNF mRNA expression in hippocampus and frontal
      cortex. Our results demonstrate that the robust behavioural differences between
      B6 and 129 mouse strains which are well studied in the literature persist in
      varied housing conditions, but the response to these conditions has different
      directionality in studied strains. EE appears to reinforce the existing coping
      strategies in both strains: B6 became more agile, sensitive and venturous in
      behavioural models, whereas 129 became even more inhibited than they are in
      standard conditions. The stimulating effect of amphetamine is decreased in 129
      animals that have been reared in EE. This may indicate desensitisation or
      inhibition of their dopamine system by EE. A frequently used biomarker in
      enrichment studies, BDNF, is a likely mediator for the long-term phenotype
      effects of EE. In this paper we demonstrate the differences of BDNF expression
      pattern in 129 and B6 mice. 

PMID- 24667363
TI  - Female-dependent impaired fear memory of adult rats induced by maternal
      separation, and screening of possible related genes in the hippocampal CA1.
AB  - Early life stress is one of the major susceptible factors for stress-related
      pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats
      suggest that rather than being overall unfavorable, early life stress may prepare
      the organism to perform optimally to stressful environments later in life. In
      this study, severely adverse early life stress was conducted by six consecutive
      hours of maternal separation (MS), from PND1 to PND21, and contextual fear
      conditioning model was used on PND90 to mimic the second stress in adulthood and
      the re-experiencing symptom of PTSD. It was observed that in this investigation
      pups experienced MS showed decreased sensibility to contextual fear conditioning
      in adulthood, and there sex plays an important role. For example, female rats
      suffered MS had much lower freezing than males and controls. Meanwhile, Morris
      water maze test indicated that MS did not impair rat's performance of spatial
      learning and memory. Furthermore, suppression subtractive hybridization (SSH) was
      used to screen the related genes of fear memory, by examining the changes of mRNA
      expression in CA1 area between female MS and control rats after contextual fear
      conditioning. Finally, nine up-regulated and one down-regulated genes, including
      beta2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is
      assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased
      sensitivity of PTSD induced by MS. 

PMID- 24667365
TI  - Clinical application of shock wave therapy (SWT) in musculoskeletal disorders.
AB  - Currently the application of shock wave therapy (SWT) in musculoskeletal
      disorders has been primarily used in the treatment of tendinopathies (proximal
      plantar fasciopathy, lateral elbow tendinopathy, calcific tendinopathy of the
      shoulder, and patellar tendinopathy, etc.) and bone defects (delayed- and non
      union of bone fractures, avascular necrosis of femoral head, etc.). Although the
      mechanism of their therapeutic effects are still unknown, the majority of
      published papers have shown positive and beneficial effects of using SWT as a
      treatment for musculoskeletal disorders, with a success rate ranging from 65% to
      91%, while the complications are low or negligible. The purpose of this paper is
      to inform the reader about the published data on the clinical application of SWT
      in the treatment of musculoskeletal disorders. In this paper, with the help of a
      literature review, indications and success rates for SWT in the treatment of
      musculoskeletal disorders are outlined, while adequate SWT parameters (e.g., rate
      of impulses, energy flux density, etc.) are defined according to the present
      state of knowledge. 

PMID- 24667364
TI  - Luteolin protects against high fat diet-induced cognitive deficits in obesity
      mice.
AB  - The epidemic and experimental studies have confirmed that the obesity can lead to
      neuroinflammation, neurodegenerative diseases and adversely affect cognition.
      Despite the numerous elucidations on the impact of obesity on cognition decline,
      the contributors to the impairments in obesity remain unclear. Male C57BL/6J mice
      were fed either a control or high-fat diet (HFD) for 16 weeks and then randomized
      into four groups treated with their respective diets for 4 weeks including
      control diet (CD); control diet+luteolin (CDL); high-fat diet (HFD), high-fat
      diet+luteolin (HFDL). The dose of luteolin was 10mg/kg, oral. We showed that
      adding luteolin in high-fat diet can significantly reduce body weight gain, food
      intake and plasma cytokines as well as improving glucose metabolism of mice on
      HFD. Importantly, we showed that luteolin treatment had the effects of
      alleviating neuroinflammation, oxidative stress and neuronal insulin resistance
      in the mouse brain, restored blood adipocytokines level to normal. Furthermore,
      luteolin increased the level of brain-derived neurotrophic factor (BDNF), the
      action of synapsin I (SYP) and postsynaptic density protein 95 (PSD-95) in the
      cortex and hippocampus as to that the behavioral performance in Morris water maze
      (MWM) and step-through task were significantly improved. These results indicate a
      previously unrecognized potential of luteolin in alleviating obesity-induced
      cognitive impairment for type-2 diabetes mellitus and Alzheimer disease (AD). 

PMID- 24667366
TI  - Heart rate and heart rate variability assessment identifies individual
      differences in fear response magnitudes to earthquake, free fall, and air puff in
      mice.
AB  - Fear behaviors and fear memories in rodents have been traditionally assessed by
      the amount of freezing upon the presentation of conditioned cues or unconditioned
      stimuli. However, many experiences, such as encountering earthquakes or
      accidental fall from tree branches, may produce long-lasting fear memories but
      are behaviorally difficult to measure using freezing parameters. Here, we have
      examined changes in heartbeat interval dynamics as physiological readout for
      assessing fearful reactions as mice were subjected to sudden air puff, free-fall
      drop inside a small elevator, and a laboratory-version earthquake. We showed that
      these fearful events rapidly increased heart rate (HR) with simultaneous
      reduction of heart rate variability (HRV). Cardiac changes can be further
      analyzed in details by measuring three distinct phases: namely, the rapid rising
      phase in HR, the maximum plateau phase during which HRV is greatly decreased, and
      the recovery phase during which HR gradually recovers to baseline values. We
      showed that durations of the maximum plateau phase and HR recovery speed were
      quite sensitive to habituation over repeated trials. Moreover, we have developed
      the fear resistance index based on specific cardiac response features. We
      demonstrated that the fear resistance index remained largely consistent across
      distinct fearful events in a given animal, thereby enabling us to compare and
      rank individual mouse's fear responsiveness among the group. Therefore, the fear
      resistance index described here can represent a useful parameter for measuring
      personality traits or individual differences in stress-susceptibility in both
      wild-type mice and post-traumatic stress disorder (PTSD) models. 

PMID- 24667367
TI  - N-acetyltransferase (nat) is a critical conjunct of photoperiodism between the
      circadian system and endocrine axis in Antheraea pernyi.
AB  - Since its discovery in 1923, the biology of photoperiodism remains a mystery in
      many ways. We sought the link connecting the circadian system to an endocrine
      switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two
      pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the
      circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results
      suggest that a melatonin pathway is present in the circadian neurons. Melatonin
      receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons
      suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a
      peak four hours after lights off in adult brain both under LD16:8 (LD) and
      LD12:12 (SD), and both the peak and the baseline levels were higher under LD than
      SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to
      10 cycles of LD, or stored at 4  degrees C for 4 months under constant darkness,
      an increase of NAT activity was observed when PTTH released ecdysone. DNA
      sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat
      transcription was turned off by clk or cyc dsRNA. dsRNA(NAT) caused dysfunction
      of photoperiodism. dsRNA(PER) upregulated nat transcription as anticipated, based
      on findings in the Drosophila melanogaster circadian system. Transcription of
      nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT) decreased melatonin
      while dsRNA(PER) increased melatonin. Thus nat, a clock controlled gene, is the
      critical link between the circadian clock and endocrine switch. MT-binding may
      release PTTH, resulting in termination of diapause. This study thus examined all
      of the basic functional units from the clock: a photoperiodic counter as an
      accumulator of mRNA(NAT), to endocrine switch for photoperiodism in A. pernyi
      showing this system is self-complete without additional device especially for
      photoperiodism.

PMID- 24667368
TI  - Protocatechuic acid improves cognitive deficits and attenuates amyloid deposits,
      inflammatory response in aged AbetaPP/PS1 double transgenic mice.
AB  - Protocatechuic acid (PCA), a phenolic compound of Radix Salviae Miltiorrhizae
      (RSM), has been found to have a protective effect on improving cognitive deficits
      in STZ-induced AD rats. The present study aimed to evaluate the potential
      protection activity of PCA on improving cognitive deficits and attenuating Abeta
      deposition and inflammatory responses in aged AbetaPP/PS1 double transgenic AD
      model mice. The results of Morris water maze test showed that PCA (100mg/kg)
      significantly prolonged the mean latency time and the path length of AbetaPP/PS1
      mice. PCA could significantly reduce the number of Abeta positive expressions in
      the hippocampus and cerebral cortex of AbetaPP/PS1 mice by immunocytochemical
      assay with Congo red staining and decrease remarkably APP expression level by
      Western blot analysis (P<0.01). The results from ELISA and Western blot analysis
      showed that the levels of inflammatory cytokines including TNF-alpha, IL-1beta,
      IL-6 and IL-8 decreased remarkably by the treatment with PCA (P<0.01). Further,
      there was a substantial increase of brain derived neurotrophic factor (BDNF) in
      the hippocampus and cerebral cortex of AbetaPP/PS1 mice treated with PCA
      (P<0.01). The present study provided confirmatory evidence that PCA significantly
      decreased Abeta deposits, APP and inflammatory response, whereas increased
      learning and memory ability, as well as enhanced BDNF level. Our findings
      indicated that PCA is an effective neuroprotective agent for AD therapy. It might
      be associated with the attenuation on Abeta deposits and inflammation responses
      involved in the process. 

PMID- 24667369
TI  - Increased eNOS levels in hereditary angioedema.
AB  - BACKGROUND: Hereditary angio-edema (HAE), characterized by recurrent episodes of
      angioedema involving the skin and the mucosa of the upper respiratory or the
      gastrointestinal tracts, results from heterozygosity for deficiency of the serine
      proteinase inhibitor (serpin), C1 inhibitor (C1-INH). OBJECTIVE: In this study,
      serum inflammatory cytokine levels and circulating endothelial cells collected
      from HAE patients during both acute attacks and asymptomatic periods were
      evaluated. METHOD: Twenty-four patients with Type I and 1 patient with Type II
      HAE in an asymptomatic period (Group I), 8 patients with Type I HAE during a mild
      to moderate acute attack (Group II) and 20 healthy subjects (13 females, mean
      age: 32.1+/-8.2years) were included. Serum IL-6, IL-8, IL-1beta, TNF-alpha,
      vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase
      (eNOS) levels were detected by ELISA. Circulating endothelial cells (CECs) and
      circulating endothelial progenitors (CEPs) were evaluated using Fluorescence
      Activated Cell Sorting (FACS). RESULTS: Serum eNOS levels of HAE patients were
      significantly higher than healthy subjects (p<0.006) while mean TNF-alpha levels
      in Group I were slightly lower (p<0.03) than Group II. There were no differences
      in terms of other inflammatory cytokines between the control subjects and HAE
      patients who were either in an asymptomatic period or experiencing an acute
      attack. CECs and CEPs were also similar. CONCLUSION: These results suggest that
      an inflammatory response is not necessary to trigger HAE attacks. On the other
      hand, increased eNOS levels might reflect a sustained hyperpermeability state in
      HAE patients.

PMID- 24667370
TI  - An auto-inducible mechanism for ionic liquid resistance in microbial biofuel
      production.
AB  - Ionic liquids (ILs) are emerging as superior solvents for numerous industrial
      applications, including the pretreatment of biomass for the microbial production
      of biofuels. However, some of the most effective ILs used to solubilize cellulose
      inhibit microbial growth, decreasing efficiency in the overall process. Here we
      identify an IL-resistance mechanism consisting of two adjacent genes from
      Enterobacter lignolyticus, a rain forest soil bacterium that is tolerant to an
      imidazolium-based IL. These genes retain their full functionality when
      transferred to an Escherichia coli biofuel host, with IL resistance established
      by an inner membrane transporter, regulated by an IL-inducible repressor.
      Expression of the transporter is dynamically adjusted in direct response to IL,
      enabling growth and biofuel production at levels of IL that are toxic to native
      strains. This natural auto-regulatory system provides the basis for engineering
      IL-tolerant microbes, which should accelerate progress towards effective
      conversion of lignocellulosic biomass to fuels and renewable chemicals. 

PMID- 24667372
TI  - Metasynthesis of research on the role of psychiatric inpatient nurses: what is
      important to staff?
AB  - BACKGROUND: Inpatient psychiatric nurses are a large workforce, but their work is
      poorly articulated and thus poorly understood outside of the professional
      inpatient community. OBJECTIVE: To learn how inpatient psychiatric nurses depict
      their work, define important aspects of their role, and view the impact of the
      unit environment on their clinical practice. DESIGN: Metasynthesis of research
      that has focused on the ideas and perceptions of inpatient psychiatric nurses
      around their role and practice on inpatient psychiatric units. RESULTS: Three
      themes emerged from the analysis; the first was an umbrella for three important
      aspects of nursing work: the nurses' efforts to forge engagement with patients;
      their activities which maintained the safety of the unit and interventions nurses
      viewed as educating/empowering patients. The second theme captures the conditions
      that enabled nurses to do this work such as a cohesive nursing team and their
      sense of self-direction in their role. The final theme centers on difficulties
      nurses encountered in enacting their role which included multiple
      responsibilities for patient care and management of the milieu; intense work
      often with low visibility and scant support within the organization. CONCLUSIONS:
      Nurses need to articulate their practice so they can assert for the staffing and
      resources needed to keep units safe and promote patients' well-being, strive
      toward quality, and promote the development of the specialty.

PMID- 24667371
TI  - Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and
      intrarectal inocula used in nonhuman primate models of HIV transmission.
AB  - Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but
      the underlying basis for this transmission bottleneck remains to be elucidated.
      Nonhuman primate models of mucosal virus transmission allow opportunities to gain
      insight into the basis of this mucosal bottleneck. We used simulated inocula
      consisting of either non-infectious vital dye or contrast dye with non-invasive
      magnetic resonance imaging (MRI) to visualize mucosal exposure and passive
      lymphatic drainage patterns following vaginal and rectal exposures in Indian
      origin rhesus macaques. Results revealed a limited overall distance of dye
      coverage from the anal verge following 1 ml (n = 8) intrarectally administered,
      which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure
      using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix,
      however dye was not detectable in the endocervix, uterus, fallopian tubes or
      ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition,
      following submucosal and intranodal injections of vital dye or MRI contrast dye
      in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic
      drainage pathways were identified as first the internal then common iliac chain
      followed by para-aortic lymph nodes. Drainage from the distal descending colon (n
      = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and
      para-aortic lymph nodes. Analysis after vaginal challenge with infectious
      SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral
      dissemination consistent with the imaging results. These results provide insights
      into potential patterns of viral dissemination that can help guide efforts to
      better elucidate the earliest events of virus transmission and potential
      intervention strategies.

PMID- 24667373
TI  - Focus issue: Refining the war on cancer.
AB  - Treating cancer involves not only stemming the growth of the primary tumor but
      also preventing its progression to metastatic disease. Advances in our
      understanding of the molecular pathways that transform healthy cells and maintain
      the proliferative advantage of tumor cells have enabled the development of
      targeted therapeutics, but preventing drug resistance and the switch to
      metastatic disease remains challenging. As this week's issue of Science Signaling
      highlights, dissection of the pathways that regulate inflammation in the tumor
      microenvironment and insight into the molecular changes that occur in cells in
      response to therapy may improve clinical strategies, particularly for aggressive
      breast and skin cancers. 

PMID- 24667374
TI  - MicroRNA circuits regulate the cancer-inflammation link.
AB  - Genetic and epigenetic perturbations are required to transform normal cells into
      cancer cells. Inflammatory signaling pathways are activated in various cancers,
      linking chronic inflammation to oncogenesis. However, the molecular circuits that
      result in sustained activation of these inflammatory factors are not yet well
      understood. In the 28 January 2014 issue of Science Signaling, Xiang et al.
      identified a microRNA-mediated anti-inflammatory circuit that is repressed
      epigenetically in receptor-negative breast cancers. A high-throughput screen for
      signal transducer and activator of transcription 3 (STAT3)-regulated microRNAs
      revealed microRNA miR-146b as a direct STAT3 target in mammary epithelial cells,
      but DNA methylation in its promoter area suppressed miR-146b expression in cancer
      cells. Overexpression of miR-146b suppressed nuclear factor kappaB (NF-kappaB)
      dependent expression of IL6 and subsequent STAT3 activation and decreased the
      STAT3-induced invasiveness and mesenchymal phenotype of breast cancer cells.
      Overall, this study contributes to our understanding of how inflammation is
      involved in oncogenic transformation. Further studies could evaluate the
      therapeutic potential of targeting this circuit in estrogen receptor-negative
      breast cancers. 

PMID- 24667375
TI  - Flipping the switch: integrin switching provides metastatic competence.
AB  - Integrin switching plays a critical role in the progression to metastatic
      disease, but the mechanism by which it contributes remains poorly understood. In
      the 11 February 2014 issue of Science Signaling, Truong et al. identified a
      transforming growth factor-beta-mediated, prometastatic switch that is activated
      by beta1 integrin inhibition in triple-negative breast cancers (TNBCs). Their
      work provides insight into the complex signaling changes that arise from integrin
      switching. Further characterization of beta-integrin switching will require
      elucidation of the distribution of specific alpha-beta integrin heterodimers and
      the role of ligand binding. Identifying the nature of the molecular interactions
      and the influence of a specific oncogenic context, including the status of driver
      mutations such as those in Myc and p53, will define the next phase in integrin
      cancer biology. 

PMID- 24667377
TI  - BRAF inhibitors induce metastasis in RAS mutant or inhibitor-resistant melanoma
      cells by reactivating MEK and ERK signaling.
AB  - Melanoma is a highly metastatic and lethal form of skin cancer. The protein
      kinase BRAF is mutated in about 40% of melanomas, and BRAF inhibitors improve
      progression-free and overall survival in these patients. However, after a
      relatively short period of disease control, most patients develop resistance
      because of reactivation of the RAF-ERK (extracellular signal-regulated kinase)
      pathway, mediated in many cases by mutations in RAS. We found that BRAF
      inhibition induces invasion and metastasis in RAS mutant melanoma cells through a
      mechanism mediated by the reactivation of the MEK (mitogen-activated protein
      kinase kinase)-ERK pathway, increased expression and secretion of interleukin 8,
      and induction of protease-dependent invasion. These events were accompanied by a
      cell morphology switch from predominantly rounded to predominantly elongated
      cells. We also observed similar responses in BRAF inhibitor-resistant melanoma
      cells. These data show that BRAF inhibitors can induce melanoma cell invasion and
      metastasis in tumors that develop resistance to these drugs. 

PMID- 24667376
TI  - Antagonism of EGFR and HER3 enhances the response to inhibitors of the PI3K-Akt
      pathway in triple-negative breast cancer.
AB  - Both abundant epidermal growth factor receptor (EGFR or ErbB1) and high activity
      of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway are common and
      therapeutically targeted in triple-negative breast cancer (TNBC). However,
      activation of another EGFR family member [human epidermal growth factor receptor
      3 (HER3) (or ErbB3)] may limit the antitumor effects of these drugs. We found
      that TNBC cell lines cultured with the EGFR or HER3 ligand EGF or heregulin,
      respectively, and treated with either an Akt inhibitor (GDC-0068) or a PI3K
      inhibitor (GDC-0941) had increased abundance and phosphorylation of HER3. The
      phosphorylation of HER3 and EGFR in response to these treatments was reduced by
      the addition of a dual EGFR and HER3 inhibitor (MEHD7945A). MEHD7945A also
      decreased the phosphorylation (and activation) of EGFR and HER3 and the
      phosphorylation of downstream targets that occurred in response to the
      combination of EGFR ligands and PI3K-Akt pathway inhibitors. In culture,
      inhibition of the PI3K-Akt pathway combined with either MEHD7945A or knockdown of
      HER3 decreased cell proliferation compared with inhibition of the PI3K-Akt
      pathway alone. Combining either GDC-0068 or GDC-0941 with MEHD7945A inhibited the
      growth of xenografts derived from TNBC cell lines or from TNBC patient tumors,
      and this combination treatment was also more effective than combining either GDC
      0068 or GDC-0941 with cetuximab, an EGFR-targeted antibody. After therapy with
      EGFR-targeted antibodies, some patients had residual tumors with increased HER3
      abundance and EGFR/HER3 dimerization (an activating interaction). Thus, we
      propose that concomitant blockade of EGFR, HER3, and the PI3K-Akt pathway in TNBC
      should be investigated in the clinical setting.

PMID- 24667378
TI  - Super-resolution microscopy reveals decondensed chromatin structure at
      transcription sites.
AB  - Remodeling of the local chromatin structure is essential for the regulation of
      gene expression. While a number of biochemical and bioimaging experiments suggest
      decondensed chromatin structures are associated with transcription, a direct
      visualization of DNA and transcriptionally active RNA polymerase II (RNA pol II)
      at super-resolution is still lacking. Here we investigate the structure of
      chromatin isolated from HeLa cells using binding activatable localization
      microscopy (BALM). The sample preparation method preserved the structural
      integrity of chromatin. Interestingly, BALM imaging of the chromatin spreads
      revealed the presence of decondensed chromatin as gap structures along the
      spreads. These gaps were enriched with phosphorylated S5 RNA pol II, and were
      sensitive to the cellular transcriptional state. Taken together, we could
      visualize the decondensed chromatin regions together with active RNA pol II for
      the first time using super-resolution microscopy. 

PMID- 24667379
TI  - Overexpression of OsMYB48-1, a novel MYB-related transcription factor, enhances
      drought and salinity tolerance in rice.
AB  - MYB-type transcription factors (TFs) play essential roles in plant growth,
      development and respond to environmental stresses. Role of MYB-related TFs of
      rice in drought stress tolerance is not well documented. Here, we report the
      isolation and characterization of a novel MYB-related TF, OsMYB48-1, of rice.
      Expression of OsMYB48-1 was strongly induced by polyethylene glycol (PEG),
      abscisic acid (ABA), H2O2, and dehydration, while being slightly induced by high
      salinity and cold treatment. The OsMYB48-1 protein was localized in the nucleus
      with transactivation activity at the C terminus. Overexpression of OsMYB48-1 in
      rice significantly improved tolerance to simulated drought and salinity stresses
      caused by mannitol, PEG, and NaCl, respectively, and drought stress was caused by
      drying the soil. In contrast to wild type plants, the overexpression lines
      exhibited reduced rate of water loss, lower malondialdehyde (MDA) content and
      higher proline content under stress conditions. Moreover, overexpression plants
      were hypersensitive to ABA at both germination and post-germination stages and
      accumulated more endogenous ABA under drought stress conditions. Further studies
      demonstrated that overexpression of OsMYB48-1 could regulate the expression of
      some ABA biosynthesis genes (OsNCED4, OsNCED5), early signaling genes (OsPP2C68,
      OSRK1) and late responsive genes (RAB21, OsLEA3, RAB16C and RAB16D) under drought
      stress conditions. Collectively, these results suggested that OsMYB48-1 functions
      as a novel MYB-related TF which plays a positive role in drought and salinity
      tolerance by regulating stress-induced ABA synthesis. 

PMID- 24667380
TI  - Small non-coding RNAs in plant-pathogenic Xanthomonas spp.
AB  - The genus Xanthomonas comprises a large group of plant-pathogenic bacteria. The
      infection and bacterial multiplication in the plant tissue depends on the type
      III secretion system and other virulence determinants. Recent studies revealed
      that bacterial virulence is also controlled at the post-transcriptional level by
      small non-coding RNAs (sRNAs). In this review, we highlight our current knowledge
      about sRNAs and RNA-binding proteins in Xanthomonas species. 

PMID- 24667381
TI  - Does a GLP-1 receptor agonist change glucose tolerance in patients treated with
      antipsychotic medications? Design of a randomised, double-blinded, placebo
      controlled clinical trial.
AB  - BACKGROUND: Metabolic disturbances, obesity and life-shortening cardiovascular
      morbidity are major clinical problems among patients with antipsychotic
      treatment. Especially two of the most efficacious antipsychotics, clozapine and
      olanzapine, cause weight gain and metabolic disturbances. Additionally, patients
      with schizophrenia-spectrum disorders not infrequently consume alcohol. Glucagon
      like peptide-1 (GLP-1) has shown to improve glycaemic control and reduce alcohol
      intake among patients with type 2 diabetes. OBJECTIVES: To investigate whether
      the beneficial effects of GLP-1 analogues on glycaemic control and alcohol
      intake, in patients with type 2 diabetes, can be extended to a population of pre
      diabetic psychiatric patients receiving antipsychotic treatment. METHODS AND
      ANALYSIS: Trial design, intervention and participants: The study is a 16-week,
      double-blinded, randomised, parallel-group, placebo-controlled clinical trial,
      designed to evaluate the effects of the GLP-1 analogue liraglutide on glycaemic
      control and alcohol intake compared to placebo in patients who are prediabetic,
      overweight (body mass index >=27 kg/m(2)), diagnosed with a schizophrenia
      spectrum disorder and on stable treatment with either clozapine or olanzapine.
      OUTCOMES: The primary endpoint is the change in glucose tolerance from baseline
      (measured by area under the curve for the plasma glucose excursion following a 4
      h 75 g oral glucose tolerance test) to follow-up at week 16. The secondary
      endpoints include changes of dysglycaemia, body weight, waist circumference,
      blood pressure, secretion of incretin hormones, insulin sensitivity and beta cell
      function, dual-energy X-ray absorption scan (body composition), lipid profile,
      liver function and measures of quality of life, daily functioning, severity of
      the psychiatric disease and alcohol consumption from baseline to follow-up at
      week 16. Status: Currently recruiting patients. ETHICS AND DISSEMINATION: Ethical
      approval has been obtained. Before screening, all patients will be provided oral
      and written information about the trial. The study will be disseminated by peer
      review publications and conference presentations. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov: NCT01845259, EudraCT: 2013-000121-31.

PMID- 24667382
TI  - Is adequate pain relief and time to analgesia associated with emergency
      department length of stay? A retrospective study.
AB  - OBJECTIVES: Evaluate the association of adequate analgesia and time to analgesia
      with emergency department (ED) length of stay (LOS). SETTING AND DESIGN: Post hoc
      analysis of real-time archived data. PARTICIPANTS: We included all consecutive ED
      patients >=18 years with pain intensity >6 (verbal numerical scale from 0 to 10),
      assigned to an ED bed, and whose pain was re-evaluated less than 1 h after
      receiving analgesic treatment. OUTCOME MEASURES: The main outcome was ED-LOS in
      patients who had adequate pain relief (AR=?50% pain intensity) compared with
      those who did not have such relief (NR). RESULTS: A total of 2033 patients (mean
      age 49.5 years; 51% men) met our inclusion criteria; 58.3% were discharged, and
      41.7% were admitted. Among patients discharged or admitted, there was no
      significant difference in ED-LOS between those with AR (median (25th-75th
      centile): 9.6 h (6.3-14.8) and 18.2 h (11.6-25.7), respectively) and NR (median
      (25th-75th centile): 9.6 h (6.6-16.0) and 17.4 h (11.3-26.5), respectively).
      After controlling for confounding factors, rapid time to analgesia (not AR) was
      associated with shorter ED-LOS of discharged and admitted patients (p<0.001 and
      <0.05, respectively). When adjusting for confounding variables, ED-LOS is
      shortened by 2 h (95% CI 1.1 to 2.8) when delay to receive analgesic is <90 min
      compared with >90 min for discharged and by 2.3 h (95% CI 0.17 to 4.4) for
      admitted patients. CONCLUSIONS: In our study, AR was not linked with short ED
      LOS. However, rapid administration of analgesia was associated with short ED-LOS.

PMID- 24667383
TI  - A national, cross-sectional survey of children's hospital-based safety resource
      centres.
AB  - OBJECTIVE: To describe the location, staffing, clientele, safety product
      disbursement patterns, education provided and sustainability of safety resource
      centres (SRCs) in US children's hospitals. METHODS: A cross-sectional survey was
      distributed to children's hospital-based SRC directors. Survey categories
      included: funding sources, customer base, items sold, items given free of charge,
      education provided and directors' needs. RESULTS: 32/38 (84.2%) SRC sites
      (affiliated with 30 hospitals) completed the survey. SRCs were in many hospital
      locations including lobby (28.1%), family resource centres (12.5%), gift
      shop/retail space (18.8%), mobile units (18.8%) and patient clinics (12.5%). 19%
      of respondents reported that their SRC was financially self-sustainable. Sales to
      patients predominated (mean of 44%); however, hospital employees made up a mean
      of 20% (range 0-60%) of sales. 78.1% of SRCs had products for children with
      special healthcare needs. Documentation kept at SRC sites included items
      purchased (96.9%), items given free of charge (65.6%) and customer demographics
      (50%). 56.3% of SRCs provided formal injury prevention education classes. The
      SRCs' directors' most important needs were finances (46.9%), staffing (50%) and
      space (46.9%). All of the directors were 'somewhat interested' or 'very
      interested' in each of the following: creation of a common SRC listserv, national
      SRC data bank and multisite SRC research platform. CONCLUSIONS: SRCs are located
      in many US children's hospitals, and can be characterised as heterogeneous in
      location, products sold, data kept and ability to be financially sustained.
      Further research is needed to determine best practices for SRCs to maximise their
      impact on injury prevention.

PMID- 24667384
TI  - RSO interview with Stan Bravenec.

PMID- 24667385
TI  - Monitoring performance of the cameras under the high dose-rate gamma ray
      environments.
AB  - CCD/CMOS cameras, loaded on a robot system, are generally used as the eye of the
      robot and monitoring unit. A major problem that arises when dealing with images
      provided by CCD/CMOS cameras under severe accident situations of a nuclear power
      plant is the presence of speckles owing to the high dose-rate gamma irradiation
      fields. To use a CCD/CMOS camera as a monitoring unit in a high radiation area,
      the legibility of the camera image in such intense gamma-radiation fields should
      therefore be defined. In this paper, the authors describe the monitoring index as
      a figure of merit of the camera's legibleness under a high dose-rate gamma ray
      irradiation environment. From a low dose-rate (10 Gy h) to a high dose-rate (200
      Gy h) level, the legible performances of the cameras owing to the speckles are
      evaluated. The numbers of speckles generated by gamma ray irradiation in the
      camera image are calculated by an image processing technique. The legibility of
      the sensor indicator (thermo/hygrometer) owing to the number of speckles is also
      presented. 

PMID- 24667386
TI  - Site-specific reference person parameters and derived concentration standards for
      the Savannah River Site.
AB  - The U.S. Department of Energy Order 458.1 states that the compliance with the 1
      mSv annual dose constraint to a member of the public may be demonstrated by
      calculating dose to the maximally exposed individual (MEI) or to a representative
      person. Historically, the MEI concept was used for dose compliance at the
      Savannah River Site (SRS) using adult dose coefficients and adult male usage
      parameters. For future compliance, SRS plans to use the representative person
      concept for dose estimates to members of the public. The representative person
      dose will be based on the reference person dose coefficients from the U.S. DOE
      Derived Concentration Technical Standard and on usage parameters specific to SRS
      for the reference and typical person. Usage parameters and dose coefficients were
      determined for inhalation, ingestion and external exposure pathways. The
      reference intake for air, water, meat, dairy, freshwater fish, saltwater
      invertebrates, produce (fruits and vegetables), and grains for the 95th
      percentile are 17.4 m d, 2.19 L d, 220.6 g d, 674 cm d, 66.4 g d, 23.0 g d, 633.4
      g d (448.5 g dand 631.7 g d) and 251.3 g d, respectively. For the 50th
      percentile: 13.4 m d, 0.809 L d, 86.4 g d, 187 cm d, 8.97 g d, 3.04 g d, 169.5 g
      d (45.9 g d and 145.6 g d), 101.3 g d, respectively. These parameters for the
      representative person were used to calculate and tabulate SRS-specific derived
      concentration standards (DCSs) for the pathways not included in DOE-STD-1196
      2011. 

PMID- 24667387
TI  - The Internet's role in a biodosimetric response to a radiation mass casualty
      event.
AB  - Response to a large-scale radiological incident could require timely medical
      interventions to minimize radiation casualties. Proper medical care requires
      knowing the victim's radiation dose. When physical dosimetry is absent, radiation
      specific chromosome aberration analysis can serve to estimate the absorbed dose
      in order to assist physicians in the medical management of radiation injuries. A
      mock exercise scenario was presented to six participating biodosimetry
      laboratories as one individual acutely exposed to Co under conditions suggesting
      whole-body exposure. The individual was not wearing a dosimeter and within 2-3 h
      of the incident began vomiting. The individual also had other medical symptoms
      indicating likelihood of a significant dose. Physicians managing the patient
      requested a dose estimate in order to develop a treatment plan. Participating
      laboratories in North and South America, Europe, and Asia were asked to evaluate
      more than 800 electronic images of metaphase cells from the patient to determine
      the dicentric yield and calculate a dose estimate with 95% confidence limits. All
      participants were blind to the physical dose until after submitting their
      estimates based on the dicentric chromosome assay (DCA). The exercise was
      successful since the mean biological dose estimate was 1.89 Gy whereas the actual
      physical dose was 2 Gy. This is well within the requirements for guidance of
      medical management. The exercise demonstrated that the most labor-intensive step
      in the entire process (visual evaluation of images) can be accelerated by taking
      advantage of world-wide expertise available on the Internet. 

PMID- 24667388
TI  - An analysis of radiation therapy medical events in New York State: the role of
      the state radiation programs in patient safety.
AB  - From 2001 through 2009, the New York State Department of Health (NYSDOH) has
      documented 244 reports of radiation therapy events, of which 228 have resulted
      from the delivery of radiation beam therapy using linear accelerators (LINACs).
      Historically, radiation therapy events involving LINACs have not been uniformly
      reported across the country because LINACs are regulated by state radiation
      control programs, and reporting requirements vary among states. The Nuclear
      Regulatory Commission's Nuclear Material Events Database (NMED) only tracks
      events involving radioactive materials (RAM). Efforts to track medical events
      involving LINACs at a national level have begun only recently. This article
      highlights the importance of tracking and analyzing all medical radiation events
      in order to improve quality of care and patient safety. An analysis of a subset
      of the data collected by the NYSDOH from 2001-2009 is presented. This subset
      consists of only events arising from the use of LINACs in radiation therapy.
      There are very few publications on errors and error rates in the use of medical
      accelerators in radiation therapy. This analysis highlights the most common types
      of errors, causes and contributing factors, areas for improvement and actions
      taken to bring this information to the regulated community. An error rate of
      0.07% per patient receiving radiation treatment is estimated using these data and
      the New York State Tumor Registry data for the same period. NY State Regulations
      governing the practice of Radiation Oncology have been revised recently to
      reflect the increased complexity in the delivery of therapeutic radiation.
      Collaboration and sharing of data such as those presented here, between federal,
      state and local regulators, professional organizations such as the Conference of
      Radiation Control Program Directors (CRCPD), American Society for Radiation
      Oncology (ASTRO), American Association of Physicists in Medicine (AAPM), American
      College of Radiology (ACR), American College of Radiation Oncology (ACRO),
      manufacturers of medical radiation equipment and software developers and the
      regulated community has begun and will contribute to improved quality of care and
      patient safety. 

PMID- 24667389
TI  - Hand calculations for transport of radioactive aerosols through sampling systems.
AB  - Workplace air monitoring programs for sampling radioactive aerosols in nuclear
      facilities sometimes must rely on sampling systems to move the air to a sample
      filter in a safe and convenient location. These systems may consist of probes,
      straight tubing, bends, contractions and other components. Evaluation of these
      systems for potential loss of radioactive aerosols is important because
      significant losses can occur. However, it can be very difficult to find fully
      described equations to model a system manually for a single particle size and
      even more difficult to evaluate total system efficiency for a polydispersed
      particle distribution. Some software methods are available, but they may not be
      directly applicable to the components being evaluated and they may not be
      completely documented or validated per current software quality assurance
      requirements. This paper offers a method to model radioactive aerosol transport
      in sampling systems that is transparent and easily updated with the most
      applicable models. Calculations are shown with the R Programming Language, but
      the method is adaptable to other scripting languages. The method has the
      advantage of transparency and easy verifiability. This paper shows how a set of
      equations from published aerosol science models may be applied to aspiration and
      transport efficiency of aerosols in common air sampling system components. An
      example application using R calculation scripts is demonstrated. The R scripts
      are provided as electronic attachments. 

PMID- 24667390
TI  - Modeling population screening process for maximizing throughputs.
AB  - Following a large-scale radiation emergency, affected populations will need to be
      screened soon after for potential contamination (external or internal). Effective
      management of the available resources can help maximize the screening
      throughputs. This paper reports the modeling results for screening throughputs in
      a population screening center using a set resource, considering two major
      variables, the arrival rate (number of people arriving at the screening center
      per minute) and the contamination probability (the probability of finding a
      contaminated group). Both the full process (including all sub-processes in a
      population screening center) and the core process (including only the screening
      sub-processes: pre-screening, portal monitoring, and whole body counting) were
      simulated. As expected, for both processes, as the arrival rate increases, the
      screening center can get overwhelmed. Interestingly, the contamination
      probability becomes a significant factor for screening throughputs only when the
      arrival rate becomes high. The results show that following an emergency, when the
      arrival rate is high, much more resources will need to be deployed to the
      population screening center or multiple screening centers will need to be
      established. 

PMID- 24667391
TI  - Effect of intraoperative high-dose remifentanil on postoperative pain: a
      prospective, double blind, randomized clinical trial.
AB  - BACKGROUND: Remifentanil, an ultra-short-acting opioid, is widely used for pain
      control during surgery. However, regular dose (RD) remifentanil exacerbates
      postoperative pain in a dose-dependent manner. Recent studies suggest that high
      dose (HD) remifentanil offers sustained analgesia in experimental studies. We
      thus hypothesized that intraoperative administration of high-dose remifentanil
      may attenuate postoperative pain. METHODS: In this prospective, randomized,
      double blind, controlled clinical study, sixty patients undergoing thyroidectomy
      (18-60 years-of-age) received an intraoperative infusion of 0.2 (RD group) or 1.2
      MUg kg(-1) min(-1) (HD group) remifentanil during thyroidectomy. A visual
      analogue scale (VAS) was used to measure pain intensity. Mechanical pain
      threshold on the forearm was assessed using von Frey filaments before surgery
      (baseline), 2 h postoperatively and 18-24 h postoperatively. The primary outcome
      was to compare the difference of VAS score at different time points after
      operation and morphine consumption 24 h postoperatively between RD and HD groups.
      The second outcome was to compare the difference of mechanical pain thresholds in
      the forearm postoperatively between RD and the HD groups. RESULTS: VAS scores
      were lower 30 min postoperatively in the HD group (1.29 +/- 1.67, 95% CI 0.64
      1.94) compared with the RD group (2.21 +/- 1.67, 95% CI 1.57-2.84) (t = 3.427, p
      = 0.0043, RD group vs. HD group). Postoperative morphine consumption was much
      lower in the HD group compared with the RD group (1.27 +/- 1.88 mg vs. 0.35 +/-
      1.25 mg, p = 0.033). In both groups, mechanical pain threshold was decreased 18
      24 h postoperatively (2.93 +/- 0.209 Ln(g) vs. 3.454 +/- 2.072 Ln(g), p = 0.032
      in RD group; 2.910 +/- 0.196 Ln(g) vs. 3.621 +/- 0.198 Ln(g), p = 0.006 in HD
      group, 18-24 h postoperatively vs baseline). CONCLUSIONS: Intraoperative
      administration of high-dose remifentanil decreased VAS scores and morphine
      consumption postoperatively. Thus, modulation of intraoperative opiates may be a
      simple and effective method of postoperative pain management. TRIAL REGISTRATION:
      This trial is registered in ClinicalTrials.gov, with the Name: Effect of Higher
      Doses of Remifentanil on Postoperative Pain in Patients Undergoing Thyroidectomy,
      and ID number: NCT01761149.

PMID- 24667392
TI  - Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in
      CCl4-induced acute hepatic injury.
AB  - We previously reported that F4/80(+) Kupffer cells are subclassified into CD68(+)
      Kupffer cells with phagocytic and ROS producing capacity, and CD11b(+) Kupffer
      cells with cytokine-producing capacity. Carbon tetrachloride (CCl4)-induced
      hepatic injury is a well-known chemical-induced hepatocyte injury. In the present
      study, we investigated the immunological role of Kupffer cells/macrophages in
      CCl4-induced hepatitis in mice. The immunohistochemical analysis of the liver and
      the flow cytometry of the liver mononuclear cells showed that clodronate liposome
      (c-lipo) treatment greatly decreased the spindle-shaped F4/80(+) or CD68(+)
      cells, while the oval-shaped F4/80+ CD11b(+) cells increased. Notably, severe
      hepatic injury induced by CCl4 was further aggravated by c-lipo-pretreatment. The
      population of CD11b(+) Kupffer cells/macrophages dramatically increased 24 hour
      (h) after CCl4 administration, especially in c-lipo-pretreated mice. The CD11b(+)
      Kupffer cells expressed intracellular TNF and surface Fas-ligand (FasL).
      Furthermore, anti-TNF Ab pretreatment (which decreased the FasL expression of
      CD11b(+) Kupffer cells), anti-FasL Ab pretreatment or gld/gld mice attenuated the
      liver injury induced by CCl4. CD1d-/- mouse and cell depletion experiments showed
      that NKT cells and NK cells were not involved in the hepatic injury. The adoptive
      transfer and cytotoxic assay against primary cultured hepatocytes confirmed the
      role of CD11b(+) Kupffer cells in CCl4-induced hepatitis. Interestingly, the
      serum MCP-1 level rapidly increased and peaked at six h after c-lipo
      pretreatment, suggesting that the MCP-1 produced by c-lipo-phagocytized CD68(+)
      Kupffer cells may recruit CD11b(+) macrophages from the periphery and bone
      marrow. The CD11b(+) Kupffer cells producing TNF and FasL thus play a pivotal
      role in CCl4-induced acute hepatic injury.

PMID- 24667393
TI  - Iron status and the acute post-exercise hepcidin response in athletes.
AB  - This study explored the relationship between serum ferritin and hepcidin in
      athletes. Baseline serum ferritin levels of 54 athletes from the control trial of
      five investigations conducted in our laboratory were considered; athletes were
      grouped according to values <30 MUg/L (SF<30), 30-50 MUg/L (SF30-50), 50-100
      MUg/L (SF50-100), or >100 MUg/L (SF>100). Data pooling resulted in each athlete
      completing one of five running sessions: (1) 8 * 3 min at 85% vVO2peak; (2) 5 * 4
      min at 90% vVO2peak; (3) 90 min continuous at 75% vVO2peak; (4) 40 min continuous
      at 75% vVO2peak; (5) 40 min continuous at 65% vVO2peak. Athletes from each
      running session were represented amongst all four groups; hence, the mean
      exercise duration and intensity were not different (p>0.05). Venous blood samples
      were collected pre-, post- and 3 h post-exercise, and were analysed for serum
      ferritin, iron, interleukin-6 (IL-6) and hepcidin-25. Baseline and post-exercise
      serum ferritin levels were different between groups (p<0.05). There were no group
      differences for pre- or post-exercise serum iron or IL-6 (p>0.05). Post-exercise
      IL-6 was significantly elevated compared to baseline within each group (p<0.05).
      Pre- and 3 h post-exercise hepcidin-25 was sequentially greater as the groups
      baseline serum ferritin levels increased (p<0.05). However, post-exercise
      hepcidin levels were only significantly elevated in three groups (SF30-50, SF50
      100, and SF>100; p<0.05). An athlete's iron stores may dictate the baseline
      hepcidin levels and the magnitude of post-exercise hepcidin response. Low iron
      stores suppressed post-exercise hepcidin, seemingly overriding any inflammatory
      driven increases.

PMID- 24667394
TI  - Acute appendicitis--we thought we knew it all?

PMID- 24667396
TI  - Spinal oncology: an innovative field of its own?

PMID- 24667397
TI  - Primary spine tumors: diagnosis and treatment.
AB  - BACKGROUND: Primary tumors are rare and those localized to a single location
      offer the potential for cure. To achieve this, early recognition of the primary
      tumor and proper workup and treatment are essential. METHODS: The authors
      reviewed the literature and best practices to provide recommendations on primary
      spine tumor treatment. Appropriate workup of primary spine tumors and treatment
      algorithms are also discussed. RESULTS: Patients suspected of a primary spine
      tumor should undergo fine-needle aspirate biopsy following consultation with the
      surgical team to ensure the biopsy tract is surgically resectable should the need
      arise. Once pathology is confirmed, metastatic workup should be performed to
      guide the level of treatment. If a localized lesion with poor radiation and
      chemotherapeutic response is diagnosed, then en bloc resection may be required
      for cure. If en bloc resection is not feasible or metastatic lesions are present,
      then radiation and medical oncology specialists must work in conjunction with the
      surgical team to determine the best treatment options. CONCLUSIONS: Patients with
      suspected primary tumors of the spine should be treated in a multidisciplinary
      fashion from the outset. With thoughtful management, these lesions offer the
      opportunity for surgical cure.

PMID- 24667398
TI  - Spinal tumor surgery: management and the avoidance of complications.
AB  - BACKGROUND: Complication avoidance is paramount to the success of any surgical
      procedure. In the case of spine tumor surgery, the risk of complications is
      increased because of the primary disease process and the radiotherapy and
      chemotherapeutics used to treat the disease. If complications do occur, then life
      saving adjuvant treatment must be delayed or withheld until the issue is
      resolved, potentially impacting overall disease control. METHODS: We reviewed the
      literature and our own best practices to provide recommendations on complication
      avoidance as well as the management of complications that may occur. Appropriate
      workup of suspected complications and treatment algorithms are also discussed.
      RESULTS: Appropriate patient selection and a multidisciplinary workup are
      imperative in the setting of spinal tumors. Intraoperative complications may be
      avoided by employing proper surgical technique and an understanding of the
      pathological changes in anatomy. Major postoperative issues include wound
      complications and spinal reconstruction failure. Preoperative surgical planning
      must include postoperative reconstruction. Patients undergoing spinal tumor
      resection should be closely monitored for local tumor recurrence, recurrence
      along the biopsy tract, and for distant metastatic disease. Any suspected
      recurrence should be closely watched, biopsied if necessary, and promptly
      treated. CONCLUSIONS: Because patients with spinal tumors are normally treated
      with a multidisciplinary approach, emphasis should be placed on the recognition
      of surgical complications beyond the surgical setting.

PMID- 24667399
TI  - Surgical management of primary and metastatic spinal tumors.
AB  - BACKGROUND: The axial skeleton is a common site for primary tumors and metastatic
      disease, with metastatic disease being much more common. Primary and metastatic
      spinal tumors have a diverse range of aggressiveness, ranging from benign lesions
      to highly infiltrative malignant tumors. METHODS: The authors reviewed the
      results of articles describing the treatment and outcomes of patients with
      metastatic disease or primary tumors of the spinal column. RESULTS: En bloc
      resection is the mainstay of treatment for malignant primary tumors of the spinal
      column. Intralesional resection is generally appropriate for benign primary
      tumors. Low-quality evidence supports the use of chemotherapy in select primary
      tumors; however, radiation therapy is often used for incompletely resected or
      unresectable lesions. Surgical considerations for the treatment of metastatic
      disease are more nuanced and require that the health care professional consider
      patient performance status and the pathology of the primary tumor. CONCLUSIONS:
      The treatment of metastatic and primary tumors of the spinal column requires a
      multidisciplinary approach in order to offer patients the best opportunity for
      long-term survival.

PMID- 24667400
TI  - Palliative strategies for the management of primary and metastatic spinal tumors.
AB  - BACKGROUND: Technological advances during the last few decades have improved the
      success rate of surgery for the treatment of malignant spinal tumors.
      Nonetheless, many patients present with widespread tumor burden and minimal life
      expectancy, which excludes them from being surgical candidates. For these
      patients, palliative management is recommended. METHODS: The authors reviewed
      prospective and retrospective clinical studies as well as case series regarding
      palliative treatments for primary and metastatic spinal tumors. RESULTS:
      Analgesics, ranging from nonopioids to strong opioids, may be used depending on
      the degree of pain. Steroids may also improve pain relief, although they are
      associated with a number of adverse events. Vertebroplasty and kyphoplasty are
      conservative treatments with high rates of pain relief and vertebral body
      stabilization. Radiotherapy is the gold standard for palliative management, with
      approximately 60% of patients experiencing a decrease in tumor-related spinal
      pain and up to 35% experiencing complete relief. Stereotactic radiosurgery
      delivers high doses of radiation to patients to provide pain relief while also
      sparing delicate anatomical structures. CONCLUSION: Palliative management of
      spinal tumors is diverse. Analgesics may be used in conjunction with radiotherapy
      and/or kyphoplasty or vertebroplasty to offer pain relief.

PMID- 24667401
TI  - Spinal neoplastic instability: biomechanics and current management options.
AB  - BACKGROUND: Often the spine is afflicted from primary or metastatic neoplastic
      disease, which can lead to instability. Instability can cause deformity, pain,
      and spinal cord compression and is an indication for surgery. Although overt
      instability is uniformly agreed upon, it is sometimes difficult for specialists
      to agree on subtle degrees of instability due to lack of objective criteria.
      METHODS: In this article, treatment options and the spine instability neoplastic
      system are discussed and the neoplastic instability literature is reviewed.
      RESULTS: The Spinal Instability Neoplastic Score helps specialists determine
      whether instability is present and when surgery may be indicated. However, other
      parameters such as spinal cord compression and extent of disease dictate whether
      surgery is the most appropriate option. A wide range of fusion techniques exists,
      each one tailored to the location of the lesion and goals for surgery.
      CONCLUSIONS: To optimize results, expert knowledge on the techniques and patient
      selection is of importance. Furthermore, a multidisciplinary approach is required
      because treatment of neoplastic disease is multimodal.

PMID- 24667402
TI  - Controversial issues in kyphoplasty and vertebroplasty in malignant vertebral
      fractures.
AB  - BACKGROUND: Kyphoplasty (KP) and vertebroplasty (VP) have been successfully
      employed in the treatment of pathological vertebral fractures. METHODS: A
      critical review of the medical literature was performed and controversial issues
      were analyzed. RESULTS: Evidence supports KP as the treatment of choice to
      control fracture pain and the possible restoration of sagittal balance, provided
      that no overt instability or myelopathy is present, the fracture is painful and
      other pain generators have been excluded, and positive radiological findings are
      present. Unilateral procedures yield similar results to bilateral ones and should
      be pursued whenever feasible. Biopsy should be routinely performed and 3 to 4
      levels may be augmented in a single operation. Higher cement filling appears to
      yield better results. Radiotherapy is complementary with KP and VP but must be
      individualized. CONCLUSIONS: In cases of painful cancer fractures, if overt
      instability or myelopathy is not present, unilateral KP should be pursued,
      whenever feasible, followed by radiotherapy. The technological advances in
      hardware and biomaterials, as well as combining KP with other modalities, will
      help ensure a safe and more effective procedure. Address.

PMID- 24667403
TI  - Management of locally advanced pancoast (superior sulcus) tumors with spine
      involvement.
AB  - BACKGROUND: The preferred treatment for locally aggressive lung cancers is triple
      modality therapy with concurrent and induction chemotherapy with radiation
      therapy followed by surgery. Patients with locally advanced T4 Pancoast tumors
      with spine involvement, without mediastinal N2 lymph node involvement and without
      distant metastases, are appropriate candidates for complete resection with
      subsequent spine reconstruction. This review addresses the questions of whether
      triple modality therapy with complete en bloc resection of locally advanced
      Pancoast tumors offers an advantage in terms of overall survival and complication
      rates compared with other therapeutic modalities or therapies with incomplete
      resection. METHODS: A comprehensive literature search was conducted using common
      medical databases. Inclusion and exclusion criteria for the articles were
      prospectively defined. The articles were independently reviewed and a consensus
      decision was made about each article. Selected papers were graded by level of
      evidence. RESULTS: A total of 1,001 abstracts and 93 articles fulfilled the
      criteria; from these studies, 14 were included in this systematic review. No
      level 1 study was found in this search. Four level 2 studies and 10 level 3
      retrospective case series were found. The overall 5-year survival rate reported
      in these studies ranged from 37% to 59% and the mortality rate ranged from 0% to
      6.9%. CONCLUSIONS: Evidence suggests that triple modality therapy with complete
      resection of locally advanced Pancoast tumors with involvement of the spine
      offers an advantage over other therapeutic modalities or therapies with
      incomplete resections.

PMID- 24667404
TI  - Separation surgery for spinal metastases: effect of spinal radiosurgery on
      surgical treatment goals.
AB  - BACKGROUND: The treatment of epidural spinal cord compression due to metastatic
      cancer represents an important clinical challenge. The NOMS (neurologic,
      oncologic, mechanical, and systemic) framework facilitates the determination of
      the optimal combination of systemic, radiation, and surgical therapies for
      individual patients. Spinal stereotactic radiosurgery (SRS) is an effective and
      safe modality for achieving durable control of local disease. Integrating SRS
      into the postoperative treatment plan allows surgical goals to be modified, thus
      decreasing the extent of tumor resection required. METHODS: Separation surgery is
      indicated for patients with spinal cord compression secondary to solid tumor
      metastases. During separation surgery, the spinal column is stabilized and the
      epidural tumor is resected without requiring significant vertebral body
      resection. RESULTS: Tumor separation from the spinal cord allows patients to
      undergo postoperative SRS. CONCLUSIONS: The combination of separation surgery and
      high-dose hypofractionated or single-fraction SRS results in high local tumor
      control at 1 year and is an effective palliative paradigm for this patient
      population.

PMID- 24667405
TI  - Controversy surrounding mammography screening? Not in our opinion.

PMID- 24667406
TI  - Female refugees: sensitive care needed.

PMID- 24667407
TI  - Caregiver perceptions and motivation for disclosing or concealing the diagnosis
      of HIV infection to children receiving HIV care in Mbarara, Uganda: a qualitative
      study.
AB  - BACKGROUND: Disclosure of the diagnosis of HIV to HIV-infected children is
      challenging for caregivers. Despite current recommendations, data suggest that
      levels of disclosure of HIV status to HIV-infected children receiving care in
      resource-limited settings are very low. Few studies describe the disclosure
      process for children in these settings, particularly the motivators, antecedent
      goals, and immediate outcomes of disclosure to HIV-infected children. This study
      examined caregivers' perception of the disclosure concept prior to disclosure,
      their motivation towards or away from disclosure, and their short- and long-term
      intentions for disclosure to their HIV-infected children. METHODS: In-depth
      interviews were conducted with primary caregivers of 40 HIV-infected children
      (ages 5-15 years) who were receiving HIV care but did not know their HIV status.
      RESULTS: Caregivers of HIV-infected children mainly perceived disclosure as a
      single event rather than a process of gradual delivery of information about the
      child's illness. They viewed disclosure as potentially beneficial both to
      children and themselves, as well as an opportunity to explain the parents' role
      in the transmission of HIV to the children. Caregivers desired to personally
      conduct the disclosure; however, most reported being over-whelmed with fear of
      negative outcomes and revealed a lack of self-efficacy towards managing the
      disclosure process. Consequently, most cope by deception to avoid or delay
      disclosure until they perceive their own readiness to disclose. CONCLUSIONS:
      Interventions for HIV disclosure should consider that caregivers may desire to be
      directly responsible for disclosure to children under their care. They, however,
      need to be empowered with practical skills to recognize opportunities to initiate
      the disclosure process early, as well as supported to manage it in a phased,
      developmentally appropriate manner. The potential role for peer counselors in the
      disclosure process deserves further study.

PMID- 24667408
TI  - Long-term results of aortic valve replacement with posterior root enlargement.
AB  - BACKGROUND: Posterior root enlargement provides the implantation of suitable
      sized prosthetic valves in patients with a small aortic root. The aim of this
      study was to evaluate the long-term results of posterior root enlargement in
      patients undergoing aortic valve replacement. METHODS: Between 1997 and 2011, 103
      patients with a small aortic annulus (indexed effective orifice area < 0.75 cm(
      2) . m(-2)) underwent aortic valve replacement with posterior aortic root
      enlargement. Forty-six (44%) patients were male. The mean age was 28.62 +/- 18.56
      years. Survivors were followed up for a mean of 45.6 +/- 32.4 months. RESULTS:
      Early mortality was 9.6%. The most common cause of early mortality was low
      cardiac output syndrome (6 patients). There were 2 (1.9%) late deaths due to
      cerebrovascular events. During the follow-up period, mild paravalvular leakage
      occurred in only one (1%) patient, and one suffered a malfunction of the
      prosthesis. A significant reduction was seen in the peak pressure gradients
      across the replaced aortic valves (p < 0.001). Moreover, a significant increase
      was noted in left ventricular ejection fraction (p = 0.001). CONCLUSIONS: Aortic
      root enlargement using the Manouguian technique can be applied with acceptable
      safety. It effectively decreases postoperative gradients and increases left
      ventricular ejection fraction. Short- and long-term mortality and morbidity rates
      are satisfactory.

PMID- 24667409
TI  - Quantitative evaluation of the cell penetrating properties of an iodinated Tyr-L
      maurocalcine analog.
AB  - L-Maurocalcine (L-MCa) is the first reported animal cell-penetrating toxin.
      Characterizing its cell penetration properties is crucial considering its
      potential as a vector for the intracellular delivery of drugs. Radiolabeling is a
      sensitive and quantitative method to follow the cell accumulation of a molecule
      of interest. An L-MCa analog containing an additional N-terminal tyrosine residue
      (Tyr-L-MCa) was synthesized, shown to fold and oxidize properly, and successfully
      radioiodinated to (125)I-Tyr-L-MCa. Using various microscopy techniques, the
      average volume of the rat line F98 glioma cells was evaluated at 8.9 to 18.9*10(
      7)MUl. (125)I-Tyr-L-MCa accumulates within cells with a dose-dependency similar
      to the one previously published using 5,6-carboxyfluorescein-L-MCa. According to
      subcellular fractionation of F98 cells, plasma membranes keep less than 3% of the
      peptide, regardless of the extracellular concentration, while the nucleus
      accumulates over 75% and the cytosol around 20% of the radioactive material.
      Taking into account both nuclear and cytosolic fractions, cells accumulate
      intracellular concentrations of the peptide that are equal to the extracellular
      concentrations. Estimation of (125)I-Tyr-L-MCa cell entry kinetics indicate a
      first rapid phase with a 5min time constant for the plasma membrane followed by
      slower processes for the cytoplasm and the nucleus. Once inside cells, the
      labeled material no longer escapes from the intracellular environment since 90%
      of the radioactivity remains 24h after washout. Dead cells were found to have a
      lower uptake than live ones. The quantitative information gained herein will be
      useful for better framing the use of L-MCa in biotechnological applications. This
      article is part of a Special Issue entitled: Calcium Signaling in Health and
      Disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann,
      Joachim Krebs, and Marc Moreau. 

PMID- 24667410
TI  - Notch4 reveals a novel mechanism regulating Notch signal transduction.
AB  - Notch4 is a divergent member of the Notch family of receptors that is primarily
      expressed in the vasculature. Its expression implies an important role for Notch4
      in the vasculature; however, mice homozygous for the Notch4(d1) knockout allele
      are viable. Since little is known about the role of Notch4 in the vasculature and
      how it functions, we further investigated Notch4 in mice and in cultured cells.
      We found that the Notch4(d1) allele is not null as it expresses a truncated
      transcript encoding most of the NOTCH4 extracellular domain. In cultured cells,
      NOTCH4 did not signal in response to ligand. Moreover, NOTCH4 inhibited
      signalling from the NOTCH1 receptor. This is the first report of cis-inhibition
      of signalling by another Notch receptor. The NOTCH4 extracellular domain also
      inhibits NOTCH1 signalling when expressed in cis, raising the possibility that
      reported Notch4 phenotypes may not be due to loss of NOTCH4 function. To better
      address the role of NOTCH4 in vivo, we generated a Notch4 null mouse in which the
      entire coding region was deleted. Notch4 null mice exhibited slightly delayed
      vessel growth in the retina, consistent with our novel finding that NOTCH4
      protein is expressed in the newly formed vasculature. These findings indicate a
      role of NOTCH4 in fine-tuning the forming vascular plexus. 

PMID- 24667411
TI  - p62 provides dual cytoprotection against oxidative stress in the retinal pigment
      epithelium.
AB  - As a signaling hub, p62/sequestosome plays important roles in cell signaling and
      degradation of misfolded proteins. p62 has been implicated as an adaptor protein
      to mediate autophagic clearance of insoluble protein aggregates in age-related
      diseases, including age-related macular degeneration (AMD), which is
      characterized by dysfunction of the retinal pigment epithelium (RPE). Our
      previous studies have shown that cigarette smoke (CS) induces oxidative stress
      and inhibits the proteasome pathway in cultured human RPE cells, suggesting that
      p62-mediated autophagy may become the major route to remove impaired proteins
      under such circumstances. In the present studies, we found that all p62 mRNA
      variants are abundantly expressed and upregulated by CS induced stress in
      cultured human RPE cells, yet isoform1 is the major translated form. We also show
      that p62 silencing exacerbated the CS induced accumulation of damaged proteins,
      both by suppressing autophagy and by inhibiting the Nrf2 antioxidant response,
      which in turn, increased protein oxidation. These effects of CS and p62 reduction
      were further confirmed in mice exposed to CS. We found that over-expression of
      p62 isoform1, but not its S403A mutant, which lacks affinity for ubiquitinated
      proteins, reduced misfolded proteins, yet simultaneously promoted an Nrf2
      mediated antioxidant response. Thus, p62 provides dual, reciprocal enhancing
      protection to RPE cells from environmental stress induced protein misfolding and
      aggregation, by facilitating autophagy and the Nrf2 mediated antioxidant
      response, which might be a potential therapeutic target against AMD. 

PMID- 24667413
TI  - Symmetry-protected topological phases from decorated domain walls.
AB  - Symmetry-protected topological phases generalize the notion of topological
      insulators to strongly interacting systems of bosons or fermions. A sophisticated
      group cohomology approach has been used to classify bosonic symmetry-protected
      topological phases, which however does not transparently predict their
      properties. Here we provide a physical picture that leads to an intuitive
      understanding of a large class of symmetry-protected topological phases in
      d=1,2,3 dimensions. Such a picture allows us to construct explicit models for the
      symmetry-protected topological phases, write down ground state wave function and
      discover topological properties of symmetry defects both in the bulk and on the
      edge of the system. We consider symmetries that include a Z2 subgroup, which
      allows us to define domain walls. While the usual disordered phase is obtained by
      proliferating domain walls, we show that symmetry-protected topological phases
      are realized when these domain walls are decorated, that is, are themselves
      symmetry-protected topological phases in one lower dimension. This construction
      works both for unitary Z2 and anti-unitary time reversal symmetry. 

PMID- 24667412
TI  - Functional studies of p.R132C, p.R149C, p.M283V, p.E431K, and a novel c.652-2A>G
      mutations of the CYP21A2 gene.
AB  - Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most
      frequent inborn error of metabolism and accounts for 90-95% of CAH cases. In the
      present work, we analyzed the functional consequence of four novel previously
      reported point CYP21A2 mutations -p.R132C, p.R149C, p.M283V, p.E431K- found in
      Argentinean 21-hydroxylase deficient patients. In addition, we report an acceptor
      splice site novel point mutation, c.652-2A>G, found in a classical patient in
      compound heterozygosity with the rare p.R483Q mutation. We performed
      bioinformatic and functional assays to evaluate the biological implication of the
      novel mutation. Our analyses revealed that the residual enzymatic activity of the
      isolated mutants coding for CYP21A2 aminoacidic substitutions was reduced to a
      lesser than 50% of the wild type with both progesterone and 17-OH progesterone as
      substrates. Accordingly, all the variants would predict mild non-classical
      alleles. In one non-classical patient, the p.E431K mutation was found in cis with
      the p.D322G one. The highest decrease in enzyme activity was obtained when both
      mutations were assayed in the same construction, with a residual activity most
      likely related to the simple virilizing form of the disease. For the c.652-2A>G
      mutation, bioinformatic tools predicted the putative use of two different cryptic
      splicing sites. Nevertheless, functional analyses revealed the use of only one
      cryptic splice acceptor site located within exon 6, leading to the appearance of
      an mRNA with a 16 nt deletion. A severe allele is strongly suggested due to the
      presence of a premature stop codon in the protein only 12 nt downstream. 

PMID- 24667414
TI  - Genetic prion disease: no role for the immune system in disease pathogenesis?
AB  - Prion diseases, which can manifest by transmissible, sporadic or genetic
      etiologies, share several common features, such as a fatal neurodegenerative
      outcome and the aberrant accumulation of proteinase K (PK)-resistant PrP forms in
      the CNS. In infectious prion diseases, such as scrapie in mice, prions first
      replicate in immune organs, then invade the CNS via ascending peripheral tracts,
      finally causing death. Accelerated neuroinvasion and death occurs when activated
      prion-infected immune cells infiltrate into the CNS, as is the case for scrapie
      infected mice induced for experimental autoimmune encephalomyelitis (EAE), a CNS
      inflammatory insult. To establish whether the immune system plays such a central
      role also in genetic prion diseases, we induced EAE in TgMHu2ME199K mice, a line
      mimicking for late onset genetic Creutzfeldt Jacob disease (gCJD), a human prion
      disease. We show here that EAE induction of TgMHu2ME199K mice neither accelerated
      nor aggravated prion disease manifestation. Concomitantly, we present evidence
      that PK-resistant PrP forms were absent from CNS immune infiltrates, and most
      surprisingly also from lymph nodes and spleens of TgMHu2ME199K mice at all ages
      and stages of disease. These results imply that the mechanism of genetic prion
      disease differs widely from that of the infectious presentation, and that the
      conversion of mutant PrPs into PK resistant forms occurs mostly/only in the CNS.
      If the absence of pathogenic PrP forms form immune organs is also true for gCJD
      patients, it may suggest their blood is devoid of prion infectivity. 

PMID- 24667415
TI  - Treatment with an antibody directed against Nogo-A delays disease progression in
      the SOD1G93A mouse model of Amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disorder in
      which motor neurons in the spinal cord and motor cortex degenerate. Although the
      majority of ALS cases are sporadic, mutations in Cu-Zn superoxide dismutase-1
      (SOD1) are causative for 10-20% of familial ALS (fALS), and recent findings show
      that a hexanucleotide repeat expansion in the C9ORF72 gene may account for >30%
      of fALS cases in Europe. SOD1(G93A) transgenic mice have a phenotype and
      pathology similar to human ALS. In both ALS patients and SOD1(G93A) mice, the
      first pathological features of disease manifest at the neuromuscular junction,
      where significant denervation occurs prior to motor neuron degeneration.
      Strategies aimed at preventing or delaying denervation may therefore be of
      benefit in ALS. In this study, we show that Nogo-A levels increase in muscle
      fibres of SOD1(G93A) mice along with the elevation of markers of neuromuscular
      dysfunction (CHRNA1/MUSK). Symptomatic treatment of SOD1(G93A) mice from 70 days
      of age with an anti-Nogo-A antibody (GSK577548) significantly improves hindlimb
      muscle innervation at 90 days, a late symptomatic stage of disease, resulting in
      increased muscle force and motor unit survival and a significant increase in
      motor neuron survival. However, not all aspects of this improvement in anti-Nogo
      A antibody-treated SOD1(G93A) mice were maintained at end-stage disease. These
      results show that treatment with anti-Nogo-A antibody significantly improves
      neuromuscular function in the SOD1(G93A) mouse model of ALS, at least during the
      earlier stages of disease and suggest that pharmacological inhibition of Nogo-A
      may be a disease-modifying approach in ALS. 

PMID- 24667417
TI  - Preliminary studies of the effects of psychological stress on circulating
      lymphocytes analyzed by synchrotron radiation based-Fourier transform infrared
      microspectroscopy.
AB  - Psychological stress is a condition that not only generates behavioral disorders
      but also disrupts homeostasis and immune activity that can exacerbate or lead to
      inflammatory diseases. The aim of this work was to study biochemical changes in
      circulating immune cells from rats under psychological stress by using
      vibrational spectroscopy. A stress model was used, where exposure to a stressor
      was repeated for 5 days. Subsequently, circulating lymphocytes were examined for
      their biomolecular vibrational fingerprints with synchrotron radiation based
      Fourier transform infrared microspectroscopy. The results showed an increased
      absorption at the ester lipid region (1720-1755 cm(-1)) in lymphocytes from
      stressed rats, suggesting lipid peroxidation. Statistical significant changes in
      wavenumber peak position and absorbance in the nucleic acid region were also
      observed (915-950 cm(-1) Z-DNA, 1090-1150 cm(-1) symmetric stretching of P-O-C,
      1200-1260 cm(-1) asymmetric PO2 and 1570-1510 cm(-1) methylated nucleotides)
      which suggest a reduction of transcriptional activity in lymphocytes from
      stressed rat. These results unravel part of the mechanisms by which psychological
      stress may affect the immune system leading to systemic consequences.

PMID- 24667416
TI  - Assays to monitor autophagy in Drosophila.
AB  - The term autophagy refers to the engulfment and degradation of cytoplasmic
      components within the lysosome. This process can benefit cells and organisms by
      removing damaged, superfluous, or harmful cellular components, and by generating
      a supply of recycled macromolecules that can support biosynthesis or energy
      production. Recent interest in autophagy has been driven by its potential role in
      several disease-related phenomena including neurodegeneration, cancer, immunity
      and aging. Drosophila provides a valuable animal model context for these studies,
      and work in this system has also begun to identify novel developmental and
      physiological roles of autophagy. Here, we provide an overview of methods for
      monitoring autophagy in Drosophila, with a special emphasis on the larval fat
      body. These methods can be used to investigate whether observed vesicles are of
      autophagic origin, to determine a relative rate of autophagic degradation, and to
      identify specific step(s) in the autophagic process in which a given gene
      functions. 

PMID- 24667418
TI  - Novel colorimetric sensors for cyanide based on azo-hydrazone tautomeric
      skeletons.
AB  - The monoazo dyes, 4-carboxyl-2, 6-dinitrophenylazohydroxynaphthalenes dyes (AZ
      01, AZ-03 and AZ-04), were evaluated as a highly selective colorimetric
      chemosensor for cyanide ion. The recognition of cyanide ion gave an obvious
      colour change from light yellow to brownish red and upon dilution with acetone
      produced a purple to lilac colour. Optimum conditions for the reaction between
      the azo dyes and cyanide ion were established at 30 degrees C for 5 min, and
      different variables affecting the reaction were carefully studied and optimised.
      Under the optimum conditions, linear relationships between the CN(-)
      concentrations and light absorption were established. Using these azo-hydrazone
      molecular switch entities, excellent selectivity towards the detection of CN(-)
      in aqueous solution over miscellaneous competitive anions was observed. Such
      selectivity mainly results from the possibility of nucleophilic attack on the azo
      hydrazone chemosensors by cyanide anions in aqueous system, which is not afforded
      by other competing anions. The cyanide chemosensor method described here should
      have potential application as a new family probes for detecting cyanide in
      aqueous solution.

PMID- 24667419
TI  - Evaluation of the photocatalytic activity of Ln3+-TiO2 nanomaterial using
      fluorescence technique for real wastewater treatment.
AB  - Evaluation the photocatalytic activity of different Ln(3+) modified TiO2
      nanomaterials using fluorescence based technique has rarely been reported. In the
      present work, xmol Ln(3+) modified TiO2 nanomaterials (Ln = Nd(3+), Sm(3+),
      Eu(3+), Gd(3+), Dy(3+) and Er(3+) ions; x = 0.005, 0.008, 0.01, 0.02 and 0.03)
      were synthesized by sol-gel method and characterized using different advanced
      techniques. The photocatalytic efficiency of the modified TiO2 expressed in the
      charge carrier separation and OH radicals formation were assigned using TiO2
      fluorescence quenching and fluorescence probe methods, respectively. The obtained
      fluorescence measurements confirm that doping treatment significantly decreases
      the electron-hole recombination probability in the obtained Ln(3+)/TiO2.
      Moreover, the rate of OH radicals formation is increased by doping. The highly
      active nanoparticles (0.02Gd(3+)/TiO2 and 0.01Eu(3+)/TiO2) were applied for
      industrial wastewater treatment using solar radiation as a renewable energy
      source.

PMID- 24667420
TI  - MRCI study on potential energy curves and spectroscopic properties of HF
      molecule.
AB  - The potential energy curves of the low-lying electronic states of Hydrogen
      fluoride (HF) have been investigated by using multireference configuration
      interaction (MRCI) approach in combination with cc-pV5Z basis sets for H and aug
      cc-pV6Z basis sets for F. Three singlet states (X(1)Sigma(+),B(1)Sigma(+),
      1(1)Delta), two triplet valence states ((3)PiV,(3)SigmaV(+)) and five triplet
      Rydberg states ((3)SigmaR1(+),(3)PiR1,(3)DeltaR1,(3)SigmaR1(-),(3)PiR2) of HF
      molecular are identified. (3)PiV and (3)SigmaV(+) states are repulsive, the
      spectroscopic parameters (De, Re, omegae, Be and Te) of the bound states are
      derived in the present work. We find that the order of energy levels of
      (3)SigmaR1(+),(3)PiR1,(3)DeltaR1 electronic states is different with other
      literatures, (3)SigmaR1(+) is the lowest in these three states, which undergoes a
      strongly avoided crossing with the valence state (3)SigmaV(+). The (3)SigmaR1(-)
      state is studied at the first time. In addition, the dipole moments (DM),
      transition dipole moments (TDM), Einstein coefficients (Av'v'') , Franck-Condon
      factors (qv'v'') and radiative lifetime (tauv') for B(1)Sigma(+)-X(1)Sigma(+)
      systems are predicted.

PMID- 24667421
TI  - Selective recognition of sulfate anions in a 95% ethanol solvent with a simple
      neutral salicylaldehyde dansyl hydrazine Schiff base tuned by Bronsted-Lowry acid
      base reaction.
AB  - A new Schiff base compound, 5-(dimethylamino)-N'-(2
      hydroxybenzylidene)naphthalene-1-sulfonohydrazide (R), has been synthesized,
      characterized, and employed as a selective fluorescence receptor for the
      recognition of sulfate anions. UV-vis absorption, fluorescence emission, (1)H NMR
      spectra and DFT calculation studies on the system have been carried out to
      determine the nature of the interactions between R and anions. The results reveal
      that the deprotonation of the phenol without the need of a strong base leads to
      the formation of a hydrogen-bonding complex with a -SO2-NH- group, which is
      responsible for the spectra changes. The deprotonation process for the
      selectivity recognition of sulfate can be tuned by the Bronsted-Lowry acid-base
      reaction in nonaqueous solutions, revealing that suitable phenolic hydroxyl
      acidity is the key factor for anion recognition selectivity.

PMID- 24667422
TI  - HCl yield and chemical kinetics study of the reaction of Cl atoms with CH3I at
      the 298K temperature using the infra-red tunable diode laser absorption
      spectroscopy.
AB  - Pulsed ArF excimer laser (193 nm)-CW infrared (IR) tunable diode laser Herriott
      type absorption spectroscopic technique has been made for the detection of
      product hydrochloric acid HCl. Absorption spectroscopic technique is used in the
      reaction chlorine atoms with methyl iodide (Cl+CH3I) to the study of kinetics on
      reaction Cl+CH3I and the yield of (HCl). The reaction of Cl+CH3I has been studied
      with the support of the reaction Cl+C4H10 (100% HCl) at temperature 298 K. In the
      reaction Cl+CH3I, the total pressure of He between 20 and 125 Torr at the
      constant concentration of [CH3I] 7.0*10(14) molecule cm(-3). In the present work,
      we estimated adduct formation is very important in the reaction Cl+CH3I and
      reversible processes as well and CH3I molecule photo-dissociated in the methyl
      [CH3] radical. The secondary chemistry has been studied as CH3+CH3ICl = product,
      and CH3I+CH3ICl = product2. The system has been modeled theoretically for
      secondary chemistry in the present work. The calculated and experimentally HCl
      yield nearly 65% at the concentration 1.00*10(14) molecule cm(-3) of [CH3I] and
      24% at the concentration 4.0*10(15) molecule cm(-3) of [CH3I], at constant
      concentration 4.85*10(12) molecule cm(-3) of [CH3], and at 7.3*10(12) molecule
      cm(-3) of [Cl]. The pressure dependent also studied product of HCl at the
      constant [CH3], [Cl] and [CH3I]. The experimental results are also very good
      matching with the modelling work at the reaction CH3+CH3ICl = product (k =
      (2.75+/-0.35)*10(-10) s(-1)) and CH3I+CH3ICl = product2 (k = 1.90+/-0.15)*10(-12)
      s(-1). The rate coefficients of the reaction CH3+CH3ICl and CH3I+CH3ICl has been
      made in the present work. The experimental results has been studied by two method
      (1) phase locked and (2) burst mode.

PMID- 24667423
TI  - Anti-inflammatory drugs interacting with Zn (II) metal ion based on thiocyanate
      and azide ligands: synthesis, spectroscopic studies, DFT calculations and
      antibacterial assays.
AB  - Zinc (II) complexes with non-steroidal anti-inflammatory drugs (NSAIDs) naproxen
      (nap) and ibuprofen (ibu) were synthesized in the presence of nitrogen donor
      ligands (thiocyanate or azide). The complexes were characterized by elemental
      analysis, FT-IR, (1)H NMR and UV-Vis spectroscopes. The binding modes of the
      ligands in complexes were established by means of molecular modeling of the
      complexes, and calculation of their IR, NMR and absorption spectra at DFT
      (TDDFT)/B3LYP level were studied. The experimental and calculated data verified
      monodentate binding through the carboxylic oxygen atoms of anti-inflammatory
      drugs in the zinc complexes. The calculated (1)H, FT-IR and UV-Vis data are in
      better agreement with the experimental results, and confirm the predicted
      tetrahedral structures for the Zn (II) complexes. In addition to DFT calculations
      of complexes, natural bond orbital (NBO) was performed at B3LYP/6-31+G(d,p) level
      of theory. Biological studies showed the antibacterial activity of zinc complexes
      against Gram-positive and Gram-negative bacterial strains. 

PMID- 24667424
TI  - beta-Cyclodextrin assisted solubilization of Cu and Cr complexes of flavonoids in
      aqueous medium: a DNA-interaction study.
AB  - Cu and Cr complexes of three flavonoids (morin, quercetin and 6-hydroxyflavone)
      were synthesized and included in beta-cyclodextrin (betaCD) with the objective of
      improving their pharmacokinetic profiles. Then binding with ds.DNA was studied to
      monitor their interactive tendencies at physiological conditions. The binding
      constants and other thermodynamic data from UV-vis spectroscopy and cyclic
      voltammetry revealed Cr-flavonoid-betaCD to interact with ds.DNA at pH-7.4
      through electrostatic mode of binding while Cu-flavonoid-betaCD can intercalate
      into DNA. The strong binding propensity of Cu-flavonoid-betaCD with ds.DNA
      encourages their application as anticancerous agent. 

PMID- 24667425
TI  - Synthesis, characterization and optoelectronic properties of a new perylene
      diimide-benzimidazole type solar light harvesting dye.
AB  - A perylene diimide type small molecule (BI-PDI) has been synthesized through
      Suzuki coupling reaction between N,N'-bis(2,6-diisopropylphenyl)-1,7
      dibromoperylene-3,4,9,10-tetracarboxylic diimide and 2-(2-hydroxyphenyl)-7-phenyl
      1H-benzimidazole-4-boronic acid. BI-PDI small molecule has showed an absorption
      band between 350 and 750 nm on thin films. HOMO and LUMO energy levels of BI-PDI
      dye have been calculated to be about -5.92 eV and -3.82 eV, respectively.
      Solution-processed bulk heterojunction (BHJ) solar cells have been constructed
      using BI-PDI as donor and [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) as
      acceptor or poly(3-hexylthiophene) (P3HT) as donor and BI-PDI as acceptor. The
      external quantum efficiencies (EQE) of the devices cover the most of the visible
      region between 400 and 700 nm for both configurations. Photovoltaic performances
      of BI-PDI-based organic solar cells are limited by the aggregation tendency of
      PDI structure and poor hole/electron mobilities of the active layer.

PMID- 24667426
TI  - A vibrational spectroscopic study of the silicate mineral inesite
      Ca2(Mn,Fe)7Si10O28(OH)?5H2O.
AB  - We have studied the hydrated hydroxyl silicate mineral inesite of formula
      Ca2(Mn,Fe)7Si10O28(OH)?5H2O using a combination of scanning electron microscopy
      with EDX and Raman and infrared spectroscopy. SEM analysis shows the mineral to
      be a pure monomineral with no impurities. Semiquantitative analysis shows a
      homogeneous phase, composed by Ca, Mn(2+), Si and P, with minor amounts of Mg and
      Fe. Raman spectrum shows well resolved component bands at 997, 1031, 1051, and
      1067 cm(-1) attributed to a range of SiO symmetric stretching vibrations of
      [Si10O28] units. Infrared bands found at 896, 928, 959 and 985 cm(-1) are
      attributed to the OSiO antisymmetric stretching vibrations. An intense broad band
      at 653 cm(-1) with shoulder bands at 608, 631 and 684 cm(-1) are associated with
      the bending modes of the OSiO units of the 6- and 8-membered rings of the
      [Si10O28] units. The sharp band at 3642 cm(-1) with shoulder bands at 3612 and
      3662 cm(-1) are assigned to the OH stretching vibrations of the hydroxyl units.
      The broad Raman band at 3420 cm(-1) with shoulder bands at 3362 and 3496 cm(-1)
      are assigned to the water stretching vibrations. The application of vibrational
      spectroscopy has enabled an assessment of the molecular structure of inesite to
      be undertaken.

PMID- 24667428
TI  - Preparation, structural and morphological studies of Ni doped titania
      nanoparticles.
AB  - TiO2 nanoparticles doped with different weight percentages (4%, 8%, 12% and 16%)
      of nickel contents were prepared by a modified sol-gel method using Titanium
      tetra iso propoxide and nickel nitrate as precursors and 2-propanol as a solvent.
      X-ray diffraction studies show that the as prepared and annealed products show
      anatase structure with average particle sizes running between of 8 and 16 nm.
      FTIR results demonstrate the presence of strong chemical bonding at the interface
      of TiO2 nanoparticles. The optical properties of bare and doped samples were
      carried out using UV-DRS and photoluminescence measurements. The surface
      morphology and the element constitution of the nickel doped TiO2 nanoparticles
      were studied by scanning electron microscope attached with energy dispersive X
      ray spectrometer arrangement. The non linear optical properties of the products
      were confirmed by Kurtz second harmonic generation (SHG) test and the output
      power generated by the nanoparticle was compared with that of potassium di
      hydrogen phosphate (KDP).

PMID- 24667427
TI  - DFT study of Raman spectra of hexakis(4-N'(-di(4-oxyphenethylamino)
      (thio)phosphonyl)-N'-methyl-diazobenzene)cyclotriphosphazene.
AB  - The FT-Raman spectrum of the hexakis(4-N'(-di(4-oxyphenethylamino)
      (thio)phosphonyl)-N'-methyl-diazobenzene)cyclotriphosphazene which is the first
      generation dendrimer G1 built from the cyclotriphosphazene core, six arms -O-C6H4
      CH=N-N(CH3)-P(S)< and twelve 4-oxyphenethylamino terminal groups -O-C6H4-(CH2)2
      NH2 G1 has been recorded. The structural optimization and normal mode analysis
      were performed for model compound C, consisting of cyclotriphosphazene core, one
      arm -O-C6H4-CH=N-N(CH3)-P(S)< and two 4-oxyphenethylamino terminal groups -O-C6H4
      (CH2)2-NH2 on the basis of the density functional theory (DFT) at the PBE/TZ2P
      level. The calculated geometrical parameters and harmonic vibrational frequencies
      are predicted in good agreement with the experimental data. It was found that G1
      has a concave lens structure with planar -O-C6H4-CH=N-N(CH3)-P(S)< fragments and
      slightly non-planar cyclotriphosphazene core. The 4-oxyphenethylamino groups
      attached to different arms show significant deviations from a symmetrical
      arrangement relative to the local planes of repeating units. The experimental
      Raman spectra of G1 dendron was interpreted by means of potential energy
      distribution. Relying on DFT calculations, as well as on experimental
      information, a spectral interpretation was proposed.

PMID- 24667429
TI  - Spectroscopic and density functional theory studies of 5,7,3',5'
      tetrahydroxyflavanone from the leaves of Olea ferruginea.
AB  - 5,7,3',5'-Tetrahydroxyflavanone (1) was isolated from the leaves of Olea
      ferruginea and a theoretical model was developed for obtaining the electronic and
      spectroscopic properties of 1. The geometric and electronic properties were
      calculated at B3LYP/6-311 G (d, p) level of Density Functional Theory (DFT). The
      theoretical data was in good agreement with the experimental one. The optimized
      geometric parameters of compound 1 were calculated for the first time. The
      theoretical vibrational frequencies of 1 were found to correlate with the
      experimental IR spectrum after a scaling factor of 0.9811. The UV and NMR
      spectral data computed theoretically were in good agreement with the experimental
      data. Electronic properties of the compound i.e., ionization potential (IP),
      electron affinity (EA), coefficients of HOMO and LUMO were estimated
      computationally for the first time which can be used to explain its antioxidant
      as well as other related activities and more active sites on it. The
      intermolecular interactions and their effects on IR frequencies, electronic and
      geometric parameters were simulated using water molecule as a model for hydrogen
      bonding with flavonoid hydroxyl groups. 

PMID- 24667430
TI  - Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and
      concentrated growth factor (CGF) in rabbit-skull defect healing.
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of platelet
      rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor
      (CGF) on bone healing. STUDY DESIGN: Twelve rabbits were included in this
      randomized, blinded, prospective study. 15-mm*10-mm-sized defects were created in
      the parietal bone, filled with PRP, PRF, CGF, and void. The bone mineral density
      and bone volume were analyzed with microscopic computed tomography (micro-CT) and
      histomorphometrics at the 6th and 12th week. RESULTS: In micro-CT analysis, bone
      mineral density and bone volume were greater in the experimental group than in
      controls at both 6th and 12th week, but not among the experimental groups.
      Similarly, histomorphometric examination revealed that more bone formation was
      seen in the experimental group. CONCLUSION: The addition of PRP, PRF, and CGF had
      significantly increased bone formation at the 6th week. The effect of PRP, PRF,
      and CGF was similar and may be useful in the future to increase the success rate
      of bone grafting.

PMID- 24667431
TI  - Constructing hierarchical submicrotubes from interconnected TiO2 nanocrystals for
      high reversible capacity and long-life lithium-ion batteries.
AB  - Here, we report a facile hydrothermal approach for synthesizing anatase TiO2
      hierarchical mesoporous submicrotubes (ATHMSs) with the aid of long-chain polymer
      as soft template. The TiO2 nanocrystals, with sizes of 6-8 nm, are well
      interconnected with each other to build tubular architectures with diameters of
      0.3-1.5 MUm and lengths of 10-25 MUm. Such highly porous structures give rise to
      very large specific surface area of 201.9 m(2) g(-1) and 136.8 m(2) g(-1) for the
      as-prepared and annealed samples, respectively. By using structurally stable
      ATHMSs as anode materials for lithium-ion batteries, they exhibited high
      reversible capacity, long cycling life and excellent cycling stability. Even
      after 1000 cycles, such ATHMS electrodes retained a reversible discharge capacity
      as high as 150 mAh g(-1) at the current density of 1700 mA g(-1), maintaining 92%
      of the initial discharge capacity (163 mAh g(-1)).

PMID- 24667433
TI  - Different phosphatidylinositol 3-phosphate asymmetries in yeast and mammalian
      autophagosomes revealed by a new electron microscopy technique.
AB  - Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid essential for
      autophagy, but the detailed distribution of PtdIns3P in the membrane of
      autophagosomes, autophagic bodies, and other organelles is unclear due to
      technical difficulties. In the present study, we examined PtdIns3P distribution
      in autophagic membranes with an electron microscopy method called the quick
      freeze freeze-fracture replica labeling method (QF-FRL), which can define the
      distribution of membrane lipids at the nanometer scale. In this method, membranes
      are split into 2 leaflets so that membrane asymmetry, i.e., differences between
      the 2 leaflets, can be defined unambiguously. As a result, PtdIns3P in the yeast
      autophagosome was found to exist much more abundantly in the lumenal leaflet
      (i.e., the leaflet facing the space between the outer and inner autophagosomal
      membranes) than in the cytoplasmic leaflet. In contrast, PtdIns3P in the
      mammalian autophagosome was confined to the cytoplasmic leaflet, showing an
      opposite asymmetry from that found in yeast. In yeast deleted for 2 cytoplasmic
      PtdIns3P phosphatases, Ymr1 and Sjl3, PtdIns3P distributed in an equivalent
      density in the 2 leaflets of the autophagosome membrane, suggesting that the
      asymmetry in wild-type yeast is generated as a result of unilateral PtdIns3P
      hydrolysis. The contrasting PtdIns3P distribution revealed in the present study
      suggested that formation of autophagic membranes may proceed in different ways in
      yeast and mammals.

PMID- 24667435
TI  - Direct evidences for sympathetic hyperactivity and baroreflex impairment in Tako
      Tsubo cardiopathy.
AB  - BACKGROUND: The exact pathophysiology of Tako-Tsubo cardiomyopathy (TTC) remains
      unknown but a role for sympathetic hyperactivity has been suggested. Up to now,
      no direct evidence of sympathetic nerve hyperactivity has been established nor
      involvement of sympathetic baroreflex identified. The aim of our study was to
      determine, by direct sympathetic nerve activity (SNS) recording if sympathetic
      nervous system activity is increased and spontaneous baroreflex control of
      sympathetic activity reduced in patients with TTC. METHODS: We included 13
      patients who presented with TTC and compared their SNS activity and spontaneous
      baroreflex control of sympathetic activity with that of 13 control patients with
      acutely decompensated chronic heart failure. SNS activity was evaluated by
      microneurography, a technique assessing muscle sympathetic nerve activity (MSNA).
      Spontaneous baroreflex control of sympathetic activity was evaluated as the
      absolute value of the slope of the regression line representing the relationship
      between spontaneous diastolic blood pressure values and concomitant SNS activity.
      Control patients were matched for age, sex, left ventricular ejection fraction
      and creatinine clearance. RESULTS: The mean age of the patients with TTC was 80
      years, all patients were women. There were no significant differences between the
      two groups of patients for blood pressure, heart rate or oxygen saturation level.
      TTC patients presented a significant increase in sympathetic nerve activity (MSNA
      median 63.3 bursts/min [interquartile range 61.3 to 66.0] vs median 55.7
      bursts/min [interquartile range 51.0 to 61.7]; p = 0.0089) and a decrease in
      spontaneous baroreflex control of sympathetic activity compared to matched
      control patients (spontaneous baroreflex control of sympathetic activity median
      0.7%burst/mmHg [interquartile range 0.4 to 1.9] vs median 2.4%burst/mmHg
      [interquartile range 1.8 to 2.9]; p = 0.005). CONCLUSIONS: We report for the
      first time, through direct measurement of sympathetic nerve activity, that
      patients with TTC exhibit elevated SNS activity associated with a decrease in
      spontaneous baroreflex control of sympathetic activity. These data may explain
      the pathophysiology and clinical presentation of patient with TTC.

PMID- 24667436
TI  - Toxicity and biodistribution of the serotype 2 recombinant adeno-associated viral
      vector, encoding Aquaporin-1, after retroductal delivery to a single mouse
      parotid gland.
AB  - In preparation for testing the safety of using serotype 2 recombinant adeno
      associated vector, encoding Aquaporin-1 to treat radiation-induced salivary gland
      damage in a phase 1 clinical trial, we conducted a 13 week GLP biodistribution
      and toxicology study using Balb/c mice. To best assess the safety of rAAV2hAQP1
      as well as resemble clinical delivery, vector (10(8), 10(9), 10(10), or 4.4 *
      10(10) vector particles/gland) or saline was delivered to the right parotid gland
      of mice via retroductal cannulation. Very mild surgically induced inflammation
      was caused by this procedure, seen in 3.6% of animals for the right parotid
      gland, and 5.3% for the left parotid gland. Long term distribution of vector
      appeared to be localized to the site of cannulation as well as the right and left
      draining submandibular lymph nodes at levels >50 copies/MUg in some animals. As
      expected, there was a dose-related increase in neutralizing antibodies produced
      by day 29. Overall, animals appeared to thrive, with no differences in mean body
      weight, food or water consumption between groups. There were no significant
      adverse effects due to treatment noted by clinical chemistry and pathology
      evaluations. Hematology assessment of serum demonstrated very limited changes to
      the white blood cell, segmented neutrophils, and hematocrit levels and were
      concluded to not be vector-associated. Indicators for liver, kidney, cardiac
      functions and general tissue damage showed no changes due to treatment. All of
      these indicators suggest the treatment is clinically safe.

PMID- 24667434
TI  - Human traumatic brain injury induces autoantibody response against glial
      fibrillary acidic protein and its breakdown products.
AB  - The role of systemic autoimmunity in human traumatic brain injury (TBI) and other
      forms of brain injuries is recognized but not well understood. In this study, a
      systematic investigation was performed to identify serum autoantibody responses
      to brain-specific proteins after TBI in humans. TBI autoantibodies showed
      predominant immunoreactivity against a cluster of bands from 38-50 kDa on human
      brain immunoblots, which were identified as GFAP and GFAP breakdown products.
      GFAP autoantibody levels increased by 7 days after injury, and were of the IgG
      subtype predominantly. Results from in vitro tests and rat TBI experiments also
      indicated that calpain was responsible for removing the amino and carboxyl
      termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody
      staining co-localized with GFAP in injured rat brain and in primary rat
      astrocytes. These results suggest that GFAP breakdown products persist within
      degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter
      living astroglia cells in culture and its presence appears to compromise glial
      cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP
      autoantibody levels from early (0-1 days) to late (7-10 days) times post injury.
      Changes in autoantibody levels were negatively correlated with outcome as
      measured by GOS-E score at 6 months, suggesting that TBI patients with greater
      anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of
      IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal
      window for assessment of brain damage in human patients. 

PMID- 24667437
TI  - Light-mediated kinetic control reveals the temporal effect of the Raf/MEK/ERK
      pathway in PC12 cell neurite outgrowth.
AB  - It has been proposed that differential activation kinetics allows cells to use a
      common set of signaling pathways to specify distinct cellular outcomes. For
      example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce
      different activation kinetics of the Raf/MEK/ERK signaling pathway and result in
      differentiation and proliferation, respectively. However, a direct and
      quantitative linkage between the temporal profile of Raf/MEK/ERK activation and
      the cellular outputs has not been established due to a lack of means to precisely
      perturb its signaling kinetics. Here, we construct a light-gated protein-protein
      interaction system to regulate the activation pattern of the Raf/MEK/ERK
      signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to
      significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the
      absence of growth factors. Compared with NGF stimulation, light stimulation
      induces longer but fewer neurites. Intermittent on/off illumination reveals that
      cells achieve maximum neurite outgrowth if the off-time duration per cycle is
      shorter than 45 min. Overall, light-mediated kinetic control enables precise
      dissection of the temporal dimension within the intracellular signal transduction
      network. 

PMID- 24667439
TI  - Nano-based systems for oil spills control and cleanup.
AB  - This paper reports the development of superhydrophobic nanocomposite systems
      which are also oleophilic. As hydrophobicity is based on low energy surface and
      surface roughness, the electrospinning technique was selected as the
      manufacturing technique. N,N' dimethylformamide (DMF) was employed as the
      polystyrene (PS) solvent. The "Tea-bag" (T-B) nanocomposite system is based on
      exfoliated graphite surrounded by PS superhydrophobic membranes. The T-B systems
      were tested regarding its adsorption and absorption rates. To test these
      properties, it was employed three different water/oil emulsions, i.e., new and
      used motor oil, which have physical properties (viscosity and specific gravity)
      similar to heavy crude oil extracted in Brazil, and vacuum pump oil (which does
      not form oil/water emulsion). It was observed that oil adsorption rate is
      dependent on oil surface tension, while the absorption rate is mainly dependent
      on membrane/exfoliated graphite surface area. Experimental data show that oil
      absorption rates ranged between 2.5g/g and 40g/g, while the adsorption rate
      oscillated from 0.32g/g/min to 0.80g/g/min. Furthermore, T-B systems were tested
      as containment barriers and sorbent materials with good results including its
      recyclability. 

PMID- 24667438
TI  - Percutaneous bone marrow transplantation using fractional ablative Erbium:YAG
      laser.
AB  - Topical application of therapeutic agents has been a mainstay in Dermatology for
      the treatment of skin disorders but is not commonly used for systemic delivery.
      For a topically applied agent to reach distant body sites it must first overcome
      the barrier function of the skin and then penetrate into deeper structures before
      reaching the systemic circulation. This has limited the use of topically applied
      agents to those having specific charge, solubility and size restrictions.
      Pretreatment of the skin with ablative fractional laser appears to enhance the
      uptake of some topically applied drugs but the ability to effectively deliver
      agents to distant sites is largely unproven. In this report we used a fractional
      ablative Erb:YAG (Erbium/Yttrium Aluminum Garnet) laser to facilitate the
      transfer of bone marrow stem cells through the skin in a murine bone marrow
      transplant model. Chimerism could be detected in the peripheral blood of
      recipient C57BL/6 mice that were pretreated with ablative fractional laser and
      had topically applied enhanced green fluorescent protein (GFP) labeled bone
      marrow cells from syngeneic donor transgenic mice. This study indicates that
      fractional laser can be used to deliver stem cells through the skin and remain
      functionally intact. 

PMID- 24667440
TI  - Association of FCGR2A with the response to infliximab treatment of patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: We aimed to assess a functional polymorphism in FCGR2A H131R, for
      association with the treatment response to Fc-containing inhibitors of tumor
      necrosis factor (TNF). METHODS: A total of 429 biologic-naive patients with
      rheumatoid arthritis collected in two sets (299 and 130) were treated during
      standard care with infliximab (INX), etanercept, or adalimumab. Response to the
      treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the
      Disease Activity Score (DAS) 28 from baseline and as the response by the European
      League Against Rheumatism (EULAR) criteria. These variables were analyzed for
      association with linear and logistic regression models that included sex,
      inhibitors of TNF, and baseline DAS28 as covariates. RESULTS: Significant
      association was found between the FCGR2A H131R polymorphism and the response to
      treatment with INX, but not with the other two TNF inhibitors. The 131R allele
      was associated with a lower change in DAS28 (P=0.04-0.008 at different times) in
      the first set of patients and confirmed in the second group of patients (P=0.026
      at 3 months of follow-up). Association was also found in the comparison between
      nonresponders and responders to INX by the EULAR criteria. CONCLUSION: We found
      an association of the FCGR2A 131R allele with poor response to INX. This finding
      could be of utility to understand the mechanisms behind treatment failure and
      contribute to biomarker panels for INX response prediction.

PMID- 24667441
TI  - Contrasting effects of singlet oxygen and hydrogen peroxide on bacterial
      community composition in a humic lake.
AB  - Light excitation of humic matter generates reactive oxygen species (ROS) in
      surface waters of aquatic ecosystems. Abundant ROS generated in humic matter rich
      lakes include singlet oxygen ((1)O2) and hydrogen peroxide (H2O2). Because these
      ROS differ in half-life time and toxicity, we compared their effects on microbial
      activity ((14)C-Leucine incorporation) and bacterial community composition (BCC)
      in surface waters of humic Lake Grosse Fuchskuhle (North-eastern Germany). For
      this purpose, experiments with water samples collected from the lake were
      conducted in July 2006, September 2008 and August 2009. Artificially increased
      (1)O2 and H2O2 concentrations inhibited microbial activity in water samples to a
      similar extent, but the effect of the respective ROS on BCC varied strongly. BCC
      analysis by 16S rRNA gene clone libraries and RT-PCR DGGE revealed ROS specific
      changes in relative abundance and activity of major bacterial groups and
      composition of dominating phylotypes. These changes were consistent in the three
      experiments performed in different years. The relative abundance of
      Polynucleobacter necessarius, Limnohabitans-related phylotypes
      (Betaproteobacteria), and Novosphingobium acidiphilum (Alphaproteobacteria)
      increased or was not affected by photo-sensitized (1)O2 exposure, but decreased
      after H2O2 exposure. The opposite pattern was found for Actinobacteria of the
      freshwater AcI-B cluster which were highly sensitive to (1)O2 but not to H2O2
      exposure. Furthermore, group-specific RT-PCR DGGE analysis revealed that particle
      attached P. necessarius and Limnohabitans-related phylotypes exhibit higher
      resistance to (1)O2 exposure compared to free-living populations. These results
      imply that (1)O2 acts as a factor in niche separation of closely affiliated
      Polynucleobacter and Limnohabitans-related phylotypes. Consequently, oxidative
      stress caused by photochemical ROS generation should be regarded as an
      environmental variable determining abundance, activity, and phylotype composition
      of environmentally relevant bacterial groups, in particular in illuminated and
      humic matter rich waters.

PMID- 24667442
TI  - Balance between a higher degree of heterosis and increased reproductive
      isolation: a strategic design for breeding inter-subspecific hybrid rice.
AB  - The application of heterosis (hybrid vigor) has brought great success to plant
      breeding, particularly of hybrid rice, achieving significant yield increases.
      Attempts to explore the heterosis of inter-subspecific hybrids between indica and
      japonica rice, which result in even greater yield increases, have greatly
      increased in the past decades. However, because of the reduced seed setting rate
      in F1 hybrids as a result of increased reproductive isolation, the application of
      inter-subspecific hybrids in rice has slowed. Understanding the balance between
      heterosis and the reproductive isolation of inter-subspecific hybrids will
      facilitate the strategic design of inter-subspecific hybrid breeding. In this
      study, five indica and seven japonica rice varieties were chosen as the parental
      lines of a complete diallel mating design. Data from six group traits from all of
      the hybrids and inbred lines were collected. We found that the grain weight per
      plant, grain number per panicle, tiller per plant, thousand grain weight and
      plant height, which reflected increased heterosis, were associated with the
      genetic divergence index (GDI) of the parents. Meanwhile, owing to the reduced
      seed setting rate, which was also associated with the parents' GDI, the grain
      production of the hybrids was negatively affected. After analyzing the
      relationships between the GDI of indica-japonica parents and the grain weight per
      plant of the F1 hybrids, an ideal GDI value (0.37) for the two indica-japonica
      parents that could provide an optimal balance between the inter-subspecific
      heterosis and reproductive isolation was proposed. Our findings will help in the
      strategic design of an inter-subspecific hybrid rice breeding program by
      identifying the ideal indica and japonica parents for a hybrid combination to
      achieve hybrid rice with an optimal yield. This strategic design of an inter
      subspecific hybrid rice breeding program will be time saving and cost effective. 

PMID- 24667443
TI  - A solution to the collective action problem in between-group conflict with within
      group inequality.
AB  - Conflict with conspecifics from neighbouring groups over territory, mating
      opportunities and other resources is observed in many social organisms, including
      humans. Here we investigate the evolutionary origins of social instincts, as
      shaped by selection resulting from between-group conflict in the presence of a
      collective action problem. We focus on the effects of the differences between
      individuals on the evolutionary dynamics. Our theoretical models predict that
      high-rank individuals, who are able to usurp a disproportional share of resources
      in within-group interactions, will act seemingly altruistically in between-group
      conflict, expending more effort and often having lower reproductive success than
      their low-rank group-mates. Similar behaviour is expected for individuals with
      higher motivation, higher strengths or lower costs, or for individuals in a
      leadership position. Our theory also provides an evolutionary foundation for
      classical equity theory, and it has implications for the origin of coercive
      leadership and for reproductive skew theory. 

PMID- 24667444
TI  - Non-thermal atmospheric pressure plasma inhibits thyroid papillary cancer cell
      invasion via cytoskeletal modulation, altered MMP-2/-9/uPA activity.
AB  - Plasma, the fourth state of matter, is defined as a partially or completely
      ionized gas that includes a mixture of electrons and ions. Advances in plasma
      physics have made it possible to use non-thermal atmospheric pressure plasma
      (NTP) in cancer research. However, previous studies have focused mainly on
      apoptotic cancer cell death mediated by NTP as a potential cancer therapy. In
      this study, we investigated the effect of NTP on invasion or metastasis, as well
      as the mechanism by which plasma induces anti-migration and anti-invasion
      properties in human thyroid papillary cancer cell lines (BHP10-3 and TPC1). Wound
      healing, pull-down, and Transwell assays demonstrated that NTP reduced cell
      migration and invasion. In addition, NTP induced morphological changes and
      cytoskeletal rearrangements, as detected by scanning electron microscopy and
      immunocytochemistry. We also examined matrix metalloproteinase (MMP)-2/-9 and
      urokinase-type plasminogen activator (uPA) activity using gelatin zymography, uPA
      assays and RT-PCR. FAK, Src, and paxillin expression was detected using Western
      blot analyses and immunocytochemistry. NTP decreased FAK, Src, and paxillin
      expression as well as MMP/uPA activity. In conclusion, NTP inhibited the invasion
      and metastasis of BHP10-3 and TPC1 cells by decreasing MMP-2/-9 and uPA
      activities and rearranging the cytoskeleton, which is regulated by the FAK/Src
      complex. These findings suggest novel actions for NTP and may aid in the
      development of new therapeutic strategies for locally invasive and metastatic
      cancers. 

PMID- 24667446
TI  - Obstetric airway management.

PMID- 24667445
TI  - The autism and schizophrenia associated gene CYFIP1 is critical for the
      maintenance of dendritic complexity and the stabilization of mature spines.
AB  - Copy number variation (CNV) at the 15q11.2 region has been identified as a
      significant risk locus for neurological and neuropsychiatric conditions such as
      schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the individual
      roles for genes at this locus in nervous system development, function and
      connectivity remain poorly understood. Haploinsufficiency of one gene in this
      region, Cyfip1, may provide a model for 15q11.2 CNV-associated neuropsychiatric
      phenotypes. Here we show that altering CYFIP1 expression levels in neurons both
      in vitro and in vivo influences dendritic complexity, spine morphology, spine
      actin dynamics and synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptor lateral diffusion. CYFIP1 is highly enriched at synapses and
      its overexpression in vitro leads to increased dendritic complexity. Neurons
      derived from Cyfip1 heterozygous animals on the other hand, possess reduced
      dendritic complexity, increased mobile F-actin and enhanced GluA2-containing AMPA
      receptor mobility at synapses. Interestingly, Cyfip1 overexpression or
      haploinsufficiency increased immature spine number, whereas activity-dependent
      changes in spine volume were occluded in Cyfip1 haploinsufficient neurons. In
      vivo, Cyfip1 heterozygous animals exhibited deficits in dendritic complexity as
      well as an altered ratio of immature-to-mature spines in hippocampal CA1 neurons.
      In summary, we provide evidence that dysregulation of CYFIP1 expression levels
      leads to pathological changes in CNS maturation and neuronal connectivity, both
      of which may contribute to the development of the neurological symptoms seen in
      ASD and SCZ.

PMID- 24667447
TI  - Phenylephrine infusions during cesarean section under spinal anesthesia.

PMID- 24667448
TI  - Oxytocin protocols for cesarean delivery.

PMID- 24667449
TI  - Anesthetic and obstetric management of the opioid-dependent parturient.

PMID- 24667450
TI  - Patient safety in obstetrics and obstetric anesthesia.

PMID- 24667451
TI  - Regional analgesic techniques for postoperative cesarean section pain.

PMID- 24667453
TI  - Preface: Obstetric anesthesia update, Volume 1--treatment protocols.

PMID- 24667454
TI  - Distinct regions of anterior cingulate cortex signal prediction and outcome
      evaluation.
AB  - A number of theories have been proposed to account for the role of anterior
      cingulate cortex (ACC) and the broader medial prefrontal cortex (mPFC) in
      cognition. The recent Prediction of Response Outcome (PRO) computational model
      casts the mPFC in part as performing two theoretically distinct functions:
      learning to predict the various possible outcomes of actions, and then evaluating
      those predictions against the actual outcomes. Simulations have shown that this
      new model can account for an unprecedented range of known mPFC effects, but the
      central theory of distinct prediction and evaluation mechanisms within ACC
      remains untested. Using combined computational neural modeling and fMRI, we show
      here that prediction and evaluation signals are indeed each represented in the
      ACC, and furthermore, they are represented in distinct regions within ACC. Our
      task independently manipulated both the number of predicted outcomes and the
      degree to which outcomes violated expectancies, the former providing assessment
      of regions sensitive to prediction and the latter providing assessment of regions
      sensitive to evaluation. Using quantitative regressors derived from the PRO
      computational model, we show that prediction-based model signals load on a
      network including the posterior and perigenual ACC, but outcome evaluation model
      signals load on the mid-dorsal ACC. These findings are consistent with distinct
      prediction and evaluation signals as posited by the PRO model and provide new
      perspective on a large set of known effects within ACC. 

PMID- 24667455
TI  - Neural repetition suppression in ventral occipito-temporal cortex occurs during
      conscious and unconscious processing of frequent stimuli.
AB  - Stimulus repetition can produce neural response attenuation in stimulus-category
      selective networks within the occipito-temporal lobe. It is hypothesized that
      this neural suppression reflects the functional sharpening of local neuronal
      assemblies which boosts information processing efficiency. This neural
      suppression phenomenon has been mainly reported during conditions of conscious
      stimulus perception. The question remains whether frequent stimuli processed in
      the absence of conscious perception also induce repetition suppression in those
      specialized networks. Using rare intracranial EEG recordings in the ventral
      occipito-temporal cortex (VOTC) of human epileptic patients we investigated
      neural repetition suppression in conditions of conscious and unconscious visual
      processing of words. To this end, we used an orthogonal design manipulating
      respectively stimulus repetition (frequent vs. unique stimuli) and conscious
      perception (masked vs. unmasked stimuli). By measuring the temporal dynamics of
      high-frequency broadband gamma activity in VOTC and testing for main and
      interaction effects, we report that early processing of words in word-form
      selective networks exhibits a temporal cascade of modulations by stimulus
      repetition and masking: neuronal attenuation initially is observed in response to
      repeated words (irrespective of consciousness), that is followed by a second
      modulation contingent upon word reportability (irrespective of stimulus
      repetition). Later on (>300ms post-stimulus), a significant effect of conscious
      perception on the extent of repetition suppression was observed. The temporal
      dynamics of consciousness, the recognition memory processes and their interaction
      revealed in this study advance our understanding of their contributions to the
      neural mechanisms of word processing in VOTC. 

PMID- 24667456
TI  - The respiratory cycle modulates brain potentials, sympathetic activity, and
      subjective pain sensation induced by noxious stimulation.
AB  - To test the hypothesis that a respiratory cycle influences pain processing, we
      conducted an experimental pain study in 10 healthy volunteers. Intraepidermal
      electrical stimulation (IES) with a concentric bipolar needle electrode was
      applied to the hand dorsum at pain perceptual threshold or four times the
      perceptual threshold to produce first pain during expiration or inspiration
      either of which was determined by the abrupt change in an exhaled CO2 level. IES
      evoked potentials (IESEPs), sympathetic skin response (SSR), digital
      plethysmogram (DPG), and subjective pain intensity rating scale were
      simultaneously recorded. With either stimulus intensity, IES during expiration
      produced weaker pain feeling compared to IES during inspiration. The mean
      amplitude of N200/P400 in IESEPs and that of SSR were smaller when IES was
      applied during expiration. The magnitude of DPG wave gradually decreased after
      IES, but a decrease in the magnitude of DPG wave was less evident when IES was
      delivered during expiration. Regardless of stimulus timing or stimulus intensity,
      pain perception was always concomitant with appearance of IESEPs and SSR, and
      changes in DPG. Our findings suggest that pain processing fluctuates during
      normal breathing and that pain is gated within the central nervous system during
      expiration. 

PMID- 24667457
TI  - Cardiometabolic implications of postpartum weight changes in the first year after
      delivery.
AB  - OBJECTIVE: The cumulative effect of postpartum weight retention from each
      pregnancy in a woman's life may contribute to her ultimate risk of diabetes and
      vascular disease. However, there is little direct evidence supporting this
      hypothesis. In this context, we sought to evaluate the cardiometabolic
      implications of patterns of postpartum weight change and the time course thereof
      in the first year after pregnancy. RESEARCH DESIGN AND METHODS: Three hundred
      five women underwent cardiometabolic characterization at recruitment in pregnancy
      and at 3 and 12 months postpartum. Based on their respective weight changes
      between prepregnancy and 3 months postpartum (loss or gain) and between 3 and 12
      months postpartum (loss or gain), participants were stratified into four groups:
      loss/loss, gain/loss, loss/gain, and gain/gain. RESULTS: Most women (81.0%) had
      higher weight at 3 months postpartum compared with prepregnancy. Between 3 and 12
      months, most women (74.4%) lost weight. At 3 months, there were modest
      differences between the four groups in mean adjusted LDL cholesterol (P = 0.01)
      and apolipoprotein-B (apoB; P = 0.02) but no significant differences in adjusted
      blood pressure, fasting and 2-h glucose, HDL, triglycerides, homeostasis model
      assessment of insulin resistance (HOMA-IR), adiponectin, and C-reactive protein.
      By 12 months postpartum, however, clear gradients emerged, with mean adjusted
      diastolic blood pressure (P = 0.02), HOMA-IR (P = 0.0003), LDL (P = 0.001), and
      apoB (P < 0.0001) all progressively increasing from the loss/loss group to
      gain/loss to loss/gain to gain/gain. Similarly, at 12 months, mean adjusted
      adiponectin showed a stepwise decrease from loss/loss to gain/loss to loss/gain
      to gain/gain (P = 0.003). CONCLUSIONS: An adverse cardiometabolic profile emerges
      as early as 1 year postpartum in women who do not lose weight between 3 and 12
      months after delivery.

PMID- 24667458
TI  - Interarm blood pressure difference in people with diabetes: measurement and
      vascular and mortality implications: a cohort study.
AB  - OBJECTIVE: Differences in blood pressure between arms are associated with
      vascular disease and increased mortality; this has not been reported in diabetes.
      We explored these associations, and assessed reference standard and pragmatic
      measurement techniques, in people with diabetes and in nondiabetic controls.
      RESEARCH DESIGN AND METHODS: A prospective cohort study in Devon, England,
      recruited 727 people with type 1 or type 2 diabetes and 285 nondiabetic controls.
      Simultaneous repeated measurements of bilateral blood pressure were made at
      recruitment. Data were used to inform a pragmatic measurement strategy. Interarm
      differences were examined for cross-sectional associations with target organ
      disease and prospective mortality associations (median follow-up 52 months).
      RESULTS: We found 8.6% of participants with diabetes and 2.9% of controls had
      systolic interarm differences >=10 mmHg. Single pairs of blood pressure
      measurements had high negative predictive values (97-99%) for excluding interarm
      differences. Systolic interarm differences >=10 mmHg in diabetes were associated
      with peripheral arterial disease (odds ratio [OR] 3.4 [95% CI 1.2-9.3]).
      Differences >=15 mmHg were associated with diabetic retinopathy (OR 5.7 [1.5
      21.6]) and chronic kidney disease (OR 7.0 [1.7-29.8]). Systolic interarm
      differences were associated prospectively with increased cardiovascular
      mortality: hazard ratios 3.5 (1.0-13.0) for >=10 mmHg and 9.0 (2.0-41.0) for >=15
      mmHg. CONCLUSIONS: Blood pressure should be measured in both arms during initial
      assessment in diabetes. Systolic interarm differences can be excluded with a
      single pair of measurements. In the population with diabetes, systolic
      differences may be associated with an increased risk of morbidity and mortality.

PMID- 24667459
TI  - Changes over time in high out-of-pocket health care burden in U.S. adults with
      diabetes, 2001-2011.
AB  - OBJECTIVE: High out-of-pocket (OOP) costs can be an obstacle to health care
      access and treatment compliance. This study investigated trends in high OOP
      health care burden in people with diabetes. RESEARCH DESIGN AND METHODS: Using
      Medical Expenditure Panel Survey 2001-2011 data, we examined trends in the
      proportion of people aged 18-64 years with diabetes facing a high OOP burden. We
      also examined whether the trend differed by insurance status (private insurance,
      public insurance, or no insurance) or by income level (poor and near poor, low
      income, middle income, or high income). RESULTS: In 2011, 23% of people with
      diabetes faced high OOP burden. Between 2001-2002 and 2011, the proportion of
      people facing high OOP burden fell by 5 percentage points (P < 0.01). The
      proportion of those who were publicly insured decreased by 22 percentage points
      (P < 0.001) and of those who were uninsured by 12 percentage points (P = 0.01).
      Among people with diabetes who were poor and near poor and those with low income,
      the proportion facing high OOP burden decreased by 21 (P < 0.001) and 13 (P =
      0.01) percentage points, respectively; no significant change occurred in the
      proportion with private insurance or middle and high incomes between 2001-2002
      and 2011. CONCLUSIONS: The past decade has seen a narrowing of insurance coverage
      and income-related disparities in high OOP burden in people with diabetes; yet,
      almost one-fourth of all people with diabetes still face a high OOP burden.

PMID- 24667460
TI  - Exploratory trial of intranasal administration of glucagon-like peptide-1 in
      Japanese patients with type 2 diabetes.
AB  - OBJECTIVE: This study aimed to assess the efficacy and safety of our newly
      developed nasal glucagon-like peptide-1 (GLP-1) compound and injector. RESEARCH
      DESIGN AND METHODS: Twenty-six patients with type 2 diabetes were enrolled in
      this double-blind placebo-controlled study. The nasal compound containing 1.2 mg
      of human GLP-1 (7-36) amide or placebo was administered immediately before every
      meal for 2 weeks. RESULTS: The plasma peak concentration of active GLP-1 was 47.2
      pmol/L, and its Tmax was 8.1 min. The early phase of insulin and glucagon
      secretion were recovered and suppressed, respectively, in the GLP-1 group.
      Glycoalbumin levels became significantly lower and 1,5-anhydroglucitol levels
      significantly higher after GLP-1 administration. No marked adverse events were
      observed after using nasal GLP-1. CONCLUSIONS: The newly developed nasal GLP-1
      compound may be a potential treatment for type 2 diabetes. The long-term
      application of the drug should be evaluated in future trials.

PMID- 24667461
TI  - Simultaneous GLP-1 and insulin administration acutely enhances their
      vasodilatory, antiinflammatory, and antioxidant action in type 2 diabetes.
AB  - OBJECTIVE: To test the hypothesis that the simultaneous administration of GLP-1
      and insulin may increase their vasodilatory, antiinflammatory, and antioxidant
      action in type 2 diabetes. RESEARCH DESIGN AND METHODS: In two groups of persons
      with type 2 diabetes, two sets of experiments were performed. The first group had
      two normoglycemic-normoinsulinemic clamps with or without GLP-1 and two
      normoglycemic-hyperinsulinemic clamps with or without GLP-1. The second group had
      two hyperglycemic-normoinsulinemic clamps and two hyperglycemic-hyperinsulinemic
      clamps with or without GLP-1. RESULTS: During the normoglycemic-hyperinsulinemic
      clamp, flow-mediated dilatation (FMD) increased, while soluble intercellular
      adhesion molecule (sICAM-1), plasma 8-iso-prostaglandin F2alpha (8-iso
      PGF2alpha), nitrotyrosine, and interleukin (IL)-6 decreased compared with
      normoglycemic-normoinsulinemic clamp. Similar results were obtained with the
      infusion of GLP-1 during the normoglycemic-normoinsulinemic clamp. The
      combination of hyperinsulinemia and GLP-1 in normoglycemia was accompanied by a
      further FMD increase and sICAM-1, 8-iso-PGF2alpha, nitrotyrosine, and IL-6
      decrease. During the hyperglycemic-normoinsulinemic clamp, FMD significantly
      decreased, while sICAM-1, 8-iso-PGF2alpha, nitrotyrosine, and IL-6 significantly
      increased. When hyperglycemia was accompanied by hyperinsulinemia or by the
      simultaneous infusion of GLP-1, these phenomena were attenuated. The simultaneous
      presence of hyperinsulinemia and GLP-1 had an increased beneficial effect.
      CONCLUSIONS: Our results show that the combination of insulin and GLP-1 is more
      effective than insulin or GLP-1 alone in improving endothelial dysfunction,
      inflammation, and oxidative stress in type 2 diabetes.

PMID- 24667462
TI  - The association between patient-reported self-management behavior, intermediate
      clinical outcomes, and mortality in patients with type 2 diabetes: results from
      the KORA-A study.
AB  - OBJECTIVE: Little is known about the impact of diabetes self-management behavior
      (SMB) on long-term outcomes. We aimed to examine the association among patient
      reported SMB, intermediate clinical outcomes, and mortality in patients with type
      2 diabetes. RESEARCH DESIGN AND METHODS: Data were collected from 340 patients
      with type 2 diabetes of the KORA-A study (1997/1998) who were recruited from two
      previous population-based surveys (n = 161) and a myocardial infarction registry
      (n = 179) in southern Germany. Based on previous methodological work, a high
      level of SMB was defined as being compliant with at least four of six different
      self-care dimensions, comprising physical exercise, foot care, blood glucose self
      monitoring, weight monitoring, having a diet plan, and keeping a diabetes diary.
      The vital status of the participants was observed until 2009. Multivariable
      linear, logistic, and Cox regression models were applied to assess the
      association with intermediate clinical outcomes at baseline and to predict
      mortality over the follow-up period, adjusted for sociodemographic, behavioral,
      and disease-related factors. RESULTS: In the cross-sectional perspective, a high
      level of SMB was weakly associated with a lower glycated hemoglobin A1c level (
      0.44% [-4.8 mmol/mol] [95% CI -0.88 to 0.00]), but not with low-density
      lipoprotein cholesterol, systolic blood pressure, or the presence of
      microalbuminuria, peripheral arterial disease, or polyneuropathy. During a mean
      follow-up time of 11.6 years, 189 patients died. SMB was a preventive factor for
      all-cause (hazard ratio 0.61 [95% CI 0.40-0.91]) and cardiovascular mortality
      (0.65 [95% CI 0.41-1.03]). CONCLUSIONS: Although measuring SMB is difficult and
      the used operationalization might be limited, our results give some indication
      that a high level of SMB is associated with prolonged life expectancy in patients
      with type 2 diabetes and highlight the potential impact of the patients' active
      contribution on the long-term trajectory of the disease. We assume that the used
      proxy for SMB is associated with unmeasured, but important, dimensions of health
      behavior.

PMID- 24667463
TI  - Hyaluronic acid gel distribution pattern in periocular area with high-resolution
      ultrasound imaging.
AB  - BACKGROUND: High-resolution ultrasound (HRUS) is a useful tool in defining
      anatomic and dynamic soft tissue relationships in the periocular area. It also
      allows visualization of hyaluronic acid (HA) gel within the soft tissue.
      OBJECTIVES: The authors investigate the difference in the distribution pattern
      between 2 HA fillers in the periocular tissue using HRUS. METHODS: The charts of
      10 patients who underwent periocular injection using HA gel filler and were
      subsequently examined with HRUS were reviewed. Half of the patients (n = 5) were
      treated with Restylane-L (Medicis Aesthetics, Inc, Scottsdale, Arizona) and the
      remaining 5 with Belotero Balance (Merz Aesthetics, Inc, San Mateo, California).
      Ultrasonographic evaluation (Logiq p6; GE Healthcare, Waukesha, Washington) was
      performed before and immediately after HA filler injection. RESULTS: The HA
      appears as a hypoechoic image within the soft tissue plane on HRUS. Restylane-L
      filler formed a localized hypoechoic image within the tissue, with some spread
      into bubbles or pearl-like configuration. Belotero Balance spread more widely
      into the tissue plane and diffused into an elongated or spindle-shaped hypoechoic
      image. CONCLUSIONS: Our preliminary data suggest that HA gel fillers with
      differing production technologies show distinct spread and distribution patterns
      in the periocular tissues on HRUS examination.

PMID- 24667464
TI  - Making the fourth year more meaningful.

PMID- 24667465
TI  - Ethical considerations for health-related service-learning programs.

PMID- 24667466
TI  - In reply to Ventres.

PMID- 24667467
TI  - Potential benefits of collaboration in short-term global health learning
      experiences.

PMID- 24667468
TI  - In reply to Loh and Lin.

PMID- 24667469
TI  - Global health training should be structured, standardized, and universal.

PMID- 24667470
TI  - In reply to Drain and Rhatigan.

PMID- 24667471
TI  - A standard for medical Spanish credentialing.

PMID- 24667472
TI  - In reply to O'Rourke and Gruener.

PMID- 24667474
TI  - Thanksgiving.

PMID- 24667475
TI  - Medicine and the arts. Work-related: a coal miner's story by Cynthia Feltner.
      Commentary.

PMID- 24667477
TI  - See what you cannot see.

PMID- 24667478
TI  - AM last page: what entrustable professional activities add to a competency-based
      curriculum.

PMID- 24667479
TI  - Characteristics and clinical impact of stimulation-evoked seizures during
      extraoperative cortical mapping.
AB  - Extraoperative electrocortical stimulation mapping (ESM) is used to identify
      functional cortex prior to epilepsy surgery, with the goal of preserving function
      postoperatively. Although attempts are made to avoid stimulation-evoked seizure
      activity, the clinical impact of these events with regard to safety, clinical
      utility, functional outcome, and even disruption to the procedure itself is
      unknown. We conducted a retrospective review of 57 patients with
      pharmacoresistant focal epilepsy who underwent intracranial electrode
      implantation and ESM. Stimulation-evoked seizures (afterdischarges associated
      with clinical signs or symptoms) occurred in 19 patients (33%). Mapping sessions
      were disrupted for 11 of these patients (i.e., 19% of the full sample and 58% of
      the subgroup of patients with stimulation-evoked seizures). Patients who had ESM
      disruption were no less likely than patients without ESM disruption to be seizure
      free at one year (p=0.63) and two years (p=0.57) postoperatively. Among 23
      patients who underwent language assessment pre- and postoperatively, 4 (17%) had
      evoked seizures that disrupted language mapping; these patients were no more
      likely to show postoperative language declines relative to those who had no ESM
      disruption (p=0.26). Results suggest that evoked seizures occur frequently during
      ESM and can disrupt the procedure; however, these events do not appear to
      adversely affect postoperative outcomes. Nevertheless, attempts should be made to
      limit stimulation-evoked seizures in order to reduce patient discomfort, increase
      efficiency, and maximize the utility of ESM. 

PMID- 24667480
TI  - Severe hippocampal atrophy is not associated with depression in temporal lobe
      epilepsy.
AB  - Depression in temporal lobe epilepsy (TLE) is common, is a strong predictor of
      subjective disability, and may have unique pathophysiological characteristics.
      Previous studies showed that reduced hippocampal volume is associated with
      significant depressive symptoms in patients with TLE. We utilized regions of
      interest analysis of high-resolution brain MRI and a reliable and valid measure
      of depressive symptoms to evaluate 28 consecutive adult subjects with video-EEG
      confirmed TLE. Regions of interest were based on prior human and animal studies
      of mood and behavioral dysfunction. Forty-three percent of the entire group had
      significant symptoms of depression, defined by a Beck Depression Inventory (BDI)
      score of greater than 15. Total hippocampal volumes were significantly smaller in
      the group with BDI<15, (p<0.007). None of the subjects in the quartile with the
      smallest left hippocampal volume had a BDI score greater than 15 compared with
      57% of the subjects in the upper three quartiles (p<0.008). No other limbic brain
      structures (amygdala, subcallosal gyrus, subgenual gyrus, gyrus rectus), or total
      cerebral volume were associated with depressive symptoms. Adequate hippocampal
      integrity may be necessary to maintain depression symptoms in mesial temporal
      lobe epilepsy. This finding also supports the possibility of a unique mechanism
      for depression in mesial temporal lobe epilepsy, such as hyperexcitable neuronal
      influence on the limbic network. 

PMID- 24667481
TI  - The origin, mechanisms, incidence and clinical consequences of chromosomal
      mosaicism in humans.
AB  - BACKGROUND: Chromosomal mosaicism, the presence of two or more distinct cell
      lines, is prevalent throughout human pre- and post-implantation development and
      can lead to genetic abnormalities, miscarriages, stillbirths or live births. Due
      to the prevalence and significance of mosaicism in the human species, it is
      important to understand the origins, mechanisms and incidence of mosaicism
      throughout development. METHODS: Literature searches were conducted utilizing
      Pubmed, with emphasis on human pre- and post-implantation mosaicism. RESULTS:
      Mosaicism persists in two separate forms: general and confined. General mosaicism
      is routine during human embryonic growth as detected by preimplantation genetic
      screening at either the cleavage or blastocyst stage, leading to mosaicism within
      both the placenta and fetus proper. Confined mosaicism has been reported in the
      brain, gonads and placenta, amongst other places. Mosaicism is derived from a
      variety of mechanisms including chromosome non-disjunction, anaphase lagging or
      endoreplication. Anaphase lagging has been implicated as the main process by
      which mosaicism arises in the preimplantation embryo. Furthermore, mosaicism can
      be caused by any one of numerous factors from paternal, maternal or exogenous
      factors such as culture media or possibly controlled ovarian hyperstimulation
      during in vitro fertilization (IVF). Mosaicism has been reported in as high as 70
      and 90% of cleavage- and blastocyst-stage embryos derived from IVF, respectively.
      CONCLUSIONS: The clinical consequences of mosaicism depend on which chromosome is
      involved, and when and where an error occurs. Mitotic rescue of a meiotic error
      or a very early mitotic error will typically lead to general mosaicism while a
      mitotic error at a specific cell lineage point typically leads to confined
      mosaicism. The clinical consequences of mosaicism are dependent on numerous
      aspects, with the consequences being unique for each event.

PMID- 24667482
TI  - NIMEFI: gene regulatory network inference using multiple ensemble feature
      importance algorithms.
AB  - One of the long-standing open challenges in computational systems biology is the
      topology inference of gene regulatory networks from high-throughput omics data.
      Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to
      benchmark network inference techniques using gene expression measurements. In
      these challenges the overall top performer was the GENIE3 algorithm. This method
      decomposes the network inference task into separate regression problems for each
      gene in the network in which the expression values of a particular target gene
      are predicted using all other genes as possible predictors. Next, using tree
      based ensemble methods, an importance measure for each predictor gene is
      calculated with respect to the target gene and a high feature importance is
      considered as putative evidence of a regulatory link existing between both genes.
      The contribution of this work is twofold. First, we generalize the regression
      decomposition strategy of GENIE3 to other feature importance methods. We compare
      the performance of support vector regression, the elastic net, random forest
      regression, symbolic regression and their ensemble variants in this setting to
      the original GENIE3 algorithm. To create the ensemble variants, we propose a
      subsampling approach which allows us to cast any feature selection algorithm that
      produces a feature ranking into an ensemble feature importance algorithm. We
      demonstrate that the ensemble setting is key to the network inference task, as
      only ensemble variants achieve top performance. As second contribution, we
      explore the effect of using rankwise averaged predictions of multiple ensemble
      algorithms as opposed to only one. We name this approach NIMEFI (Network
      Inference using Multiple Ensemble Feature Importance algorithms) and show that
      this approach outperforms all individual methods in general, although on a
      specific network a single method can perform better. An implementation of NIMEFI
      has been made publicly available. 

PMID- 24667483
TI  - Does postponement of first pregnancy increase gender differences in sickness
      absence? A register based analysis of Norwegian employees in 1993-2007.
AB  - BACKGROUND: From 1970-2012, the average age at first delivery increased from 23.2
      28.5 in Norway. Postponement of first pregnancy increases risks of medical
      complications both during and after pregnancy. Sickness absence during pregnancy
      has over the last two decades increased considerably more than in non-pregnant
      women. The aim of this paper is twofold: Firstly to investigate if postponement
      of pregnancy is related to increased sickness absence and thus contributing to
      the increased gender difference in sickness absence; and secondly, to estimate
      how much of the increased gender difference in sickness absence that can be
      accounted for by increased sickness absence amongst pregnant women. METHODS: We
      employed registry-data to analyse sickness absence among all Norwegian employees
      with income equivalent to full-time work in the period 1993-2007. RESULTS: After
      control for age, education, and income, pregnant women's sickness absence (age 20
      44) increased on average 0.94 percentage points each year, compared to 0.29 in
      non-pregnant women and 0.14 in men. In pregnant women aged 20-24, sickness
      absence during pregnancy increased by 0.96 percent points per calendar year,
      compared to 0.60 in age-group 30-34. Sickness absence during pregnancy accounted
      for 25% of the increased gender gap in sickness absence, accounting for changes
      in education, income and age. CONCLUSIONS: Postponement of first pregnancy does
      not explain the increase in pregnant women's sickness absence during the period
      1993-2007 as both the highest level and increase in sickness absence is seen in
      the younger women. Reasons are poorly understood, but still important as it
      accounts for 25% of the increased gender gap in sickness absence.

PMID- 24667485
TI  - Mucormycosis outbreak associated with hospital linens.
AB  - BACKGROUND: Mucormycosis is an invasive fungal infection with a high fatality
      rate. We investigated an outbreak of mucormycosis in a pediatric hospital to
      determine routes of pathogen transmission from the environment and prevent
      additional infections. METHODS: A case was defined as a hospital-onset illness
      consistent with mucormycosis, confirmed by culture or histopathology. Case
      patient medical records were reviewed for clinical course and exposure to items
      and locations within the hospital. Environmental samples were collected from air
      and surfaces. Fungal isolates collected from case-patients and the environmental
      samples were identified using DNA sequencing. RESULTS: Five case-patients had
      hospital-associated cutaneous mucormycosis over an 11-month period; all
      subsequently died. Three case-patients had conditions known to be associated with
      susceptibility to mucormycosis, while 2 had cardiac conditions with persistent
      acidosis. The cases occurred on several different wards throughout the hospital,
      and hospital linens were the only exposure identified as common to the case
      patients. Rhizopus species were recovered from 26 (42%) of 62 environmental
      samples from clean linens and associated areas and from 1 (4%) of 25 samples from
      nonlinen-related items. Case-patients were infected with Rhizopus delemar, which
      was also isolated from cultures of clean linens and clean linen delivery bins
      from the off-site laundry facility. CONCLUSIONS: Hospital linens were identified
      as a vehicle that carried R. delemar into contact with susceptible patients.
      Fungal species identification using DNA-based methods is useful for corroborating
      epidemiologic links in hospital outbreak investigations. Hospital linens should
      be laundered, packaged, shipped and stored in a manner that minimizes exposure to
      environmental contaminants.

PMID- 24667484
TI  - Cortical and spinal mechanisms of task failure of sustained submaximal fatiguing
      contractions.
AB  - In this and the subsequent companion paper, results are presented that
      collectively seek to delineate the contribution that supraspinal circuits have in
      determining the time to task failure (TTF) of sustained submaximal contractions.
      The purpose of this study was to compare adjustments in supraspinal and spinal
      excitability taken concurrently throughout the performance of two different
      fatigue tasks with identical mechanical demands but different TTF (i.e., force
      matching and position-matching tasks). On separate visits, ten healthy volunteers
      performed the force-matching or position-matching task at 15% of maximum strength
      with the elbow flexors to task failure. Single-pulse transcranial magnetic
      stimulation (TMS), paired-pulse TMS, paired cortico-cervicomedullary stimulation,
      and brachial plexus electrical stimulation were delivered in a 6-stimuli sequence
      at baseline and every 2-3 minutes throughout fatigue-task performance. Contrary
      to expectations, the force-matching task TTF was 42% shorter (17.5 +/- 7.9 min)
      than the position-matching task (26.9 +/- 15.11 min; p<0.01); however, both tasks
      caused the same amount of muscle fatigue (p = 0.59). There were no task-specific
      differences for the total amount or rate of change in the neurophysiologic
      outcome variables over time (p>0.05). Therefore, failure occurred after a similar
      mean decline in motorneuron excitability developed (p<0.02, ES = 0.35-0.52)
      coupled with a similar mean increase in measures of corticospinal excitability
      (p<0.03, ES = 0.30-0.41). Additionally, the amount of intracortical inhibition
      decreased (p<0.03, ES = 0.32) and the amount of intracortical facilitation
      (p>0.10) and an index of upstream excitation of the motor cortex remained
      constant (p>0.40). Together, these results suggest that as fatigue develops prior
      to task failure, the increase in corticospinal excitability observed in
      relationship to the decrease in spinal excitability results from a combination of
      decreasing intracortical inhibition with constant levels of intracortical
      facilitation and upstream excitability that together eventually fail to provide
      the input to the motor cortex necessary for descending drive to overcome the
      spinal cord resistance, thereby contributing to task failure.

PMID- 24667486
TI  - Lymph node-independent liver metastasis in a model of metastatic colorectal
      cancer.
AB  - Deciphering metastatic routes is critically important as metastasis is a primary
      cause of cancer mortality. In colorectal cancer (CRC), it is unknown whether
      liver metastases derive from cancer cells that first colonize intestinal lymph
      nodes, or whether such metastases can form without prior lymph node involvement.
      A lack of relevant metastatic CRC models has precluded investigations into
      metastatic routes. Here we describe a metastatic CRC mouse model and show that
      liver metastases can manifest without a lymph node metastatic intermediary.
      Colorectal tumours transplanted onto the colonic mucosa invade and metastasize to
      specific target organs including the intestinal lymph nodes, liver and lungs.
      Importantly, this metastatic pattern differs from that observed following caecum
      implantation, which invariably involves peritoneal carcinomatosis. Anti
      angiogenesis inhibits liver metastasis, yet anti-lymphangiogenesis does not
      impact liver metastasis despite abrogating lymph node metastasis. Our data
      demonstrate direct hematogenous spread as a dissemination route that contributes
      to CRC liver malignancy. 

PMID- 24667487
TI  - Efficacy of levomilnacipran extended-release in improving functional impairment
      associated with major depressive disorder: pooled analyses of five double-blind,
      placebo-controlled trials.
AB  - Major depressive disorder (MDD) is characterized by increased rates of impaired
      function and disability. During antidepressant treatment, functional improvement
      often lags behind symptomatic resolution, and residual impairment is associated
      with an increased risk for relapse. When evaluating MDD treatments, it is
      important to assess not only depressive symptoms but also functional outcomes. In
      this post-hoc analysis, data from five studies were pooled to examine the effect
      of levomilnacipran extended-release (ER) versus placebo on functional impairment
      as measured using the Sheehan Disability Scale. The mean change in the Sheehan
      Disability Scale total score was significantly greater for levomilnacipran ER
      versus placebo in the overall pooled population, for both sexes, and across all
      ages. Statistically significantly higher rates of functional response, functional
      remission, combined (functional and symptomatic) response, and combined remission
      were achieved with levomilnacipran ER compared with placebo in the pooled
      population, as well as in the male, female, younger, and middle-aged population
      subgroups. The levomilnacipran ER group also showed significantly improved
      functional outcomes versus placebo regardless of baseline depression severity.
      Similarly, functional impairment was significantly improved and higher functional
      and combined response and remission rates were achieved with levomilnacipran ER
      compared with placebo regardless of the baseline level of functional impairment. 

PMID- 24667488
TI  - Beneficial effect of low-dose mirtazapine in acute aripiprazole-induced
      akathisia.
AB  - Low-dose mirtazapine was found to be efficacious for neuroleptic-induced
      akathisia. We evaluated whether mirtazapine is also effective for akathisia
      induced by the partial dopamine D2 receptor agonist aripiprazole. Medical charts
      were retrospectively analyzed for eight patients who developed akathisia while
      being treated with aripiprazole. All scored at least 2 (mild akathisia) on the
      Barnes Akathisia Rating Scale (BARS) and were treated with mirtazapine (15
      mg/day) for a mean of 8.5 days. There was a statistically significant reduction
      in the BARS subjective, distress, and global (P<0.01 to P<0.001), but not
      objective (P=0.21) subscales. Five (62.5%) patients fulfilled the criteria of
      response, a decrease of at least two points on the BARS global subscale. Low-dose
      mirtazapine was well tolerated, and mild sedation, the only side effect (three
      patients), was transient. A large-scale controlled investigation is warranted to
      substantiate clinical utility of mirtazapine for akathisia induced by
      aripiprazole and other second-generation antipsychotics. 

PMID- 24667489
TI  - Time-efficient myocardial contrast partition coefficient measurement from early
      enhancement with magnetic resonance imaging.
AB  - OBJECTIVE: Our purpose was to validate an early enhancement time point for
      accurately measuring the myocardial contrast partition coefficient (lambda) using
      dynamic-equilibrium magnetic resonance imaging. MATERIALS AND METHODS: The pre-
      and post-contrast longitudinal relaxation rates (reciprocal of T1) of the
      interventricular septum (R1(m)) and blood pool (R1(b)) were obtained from fifteen
      healthy volunteers and three diabetic patients with hypertension using two
      optimized T1 mapping sequences (modified Look-Locker inversion recovery) on a 3
      Tesla magnetic resonance scanner. Reference lambda values were calculated as the
      slope of the regression line of R1(m) versus R1(b) at dynamic equilibrium (multi
      point regression method). The simplified pre-/post-enhancement two-acquisition
      method (two-point method) was used to calculate lambda by relating the change in
      R1(m) and R1(b) using different protocols according to the acquisition stage of
      the post-enhancement data point. The agreement with the referential method was
      tested by calculating Pearson's correlation coefficient and the intra-class
      correlation coefficient. RESULTS: The lambda values measured by the two-point
      method increased (from 0.479 +/- 0.041 to 0.534 +/- 0.043) over time from 6 to 45
      minutes after contrast and exhibited good correlation with the reference at each
      time point (r >= 0.875, p<0.05). The intra-class correlation coefficient on
      absolute agreement with the reference lambda was 0.946, 0.929 and 0.922 at the
      6th, 7th and 8th minutes and dropped from 0.878 to 0.403 from the 9th minute on.
      CONCLUSIONS: The time-efficient two-point method at 6-8 minutes after the Gd-DTPA
      bolus injection exhibited good agreement with the multi-point regression method
      and can be applied for accurate lambda measurement in normal myocardium.

PMID- 24667490
TI  - Activation of platelet-derived growth factor receptor alpha contributes to liver
      fibrosis.
AB  - Chronic liver injury leads to fibrosis, cirrhosis, and loss of liver function.
      Liver cirrhosis is the 12th leading cause of death in the United States, and it
      is the primary risk factor for developing liver cancer. Fibrosis and cirrhosis
      result from activation of hepatic stellate cells (HSCs), which are the primary
      collagen producing cell type in the liver. Here, we show that platelet-derived
      growth factor receptor alpha (PDGFRalpha) is expressed by human HSCs, and
      PDGFRalpha expression is elevated in human liver disease. Using a green
      fluorescent protein (GFP) reporter mouse strain, we evaluated the role of
      PDGFRalpha in liver disease in mice and found that mouse HSCs express PDGFRalpha
      and expression is upregulated during carbon tetrachloride (CCl4) induced liver
      injury and fibrosis injection. This fibrotic response is reduced in Pdgfralpha
      heterozygous mice, consistent with the hypothesis that liver fibrosis requires
      upregulation and activation of PDGFRalpha. These results indicate that Pdgfralpha
      expression is important in the fibrotic response to liver injury in humans and
      mice, and suggest that blocking PDGFRalpha-specific signaling pathways in HSCs
      may provide therapeutic benefit for patients with chronic liver disease. 

PMID- 24667491
TI  - Contradictory reasoning network: an EEG and FMRI study.
AB  - Contradiction is a cornerstone of human rationality, essential for everyday life
      and communication. We investigated electroencephalographic (EEG) and functional
      magnetic resonance imaging (fMRI) in separate recording sessions during
      contradictory judgments, using a logical structure based on categorical
      propositions of the Aristotelian Square of Opposition (ASoO). The use of ASoO
      propositions, while controlling for potential linguistic or semantic confounds,
      enabled us to observe the spatial temporal unfolding of this contradictory
      reasoning. The processing started with the inversion of the logical operators
      corresponding to right middle frontal gyrus (rMFG-BA11) activation, followed by
      identification of contradictory statement associated with in the right inferior
      frontal gyrus (rIFG-BA47) activation. Right medial frontal gyrus (rMeFG, BA10)
      and anterior cingulate cortex (ACC, BA32) contributed to the later stages of
      process. We observed a correlation between the delayed latency of rBA11 response
      and the reaction time delay during inductive vs. deductive reasoning. This
      supports the notion that rBA11 is crucial for manipulating the logical operators.
      Slower processing time and stronger brain responses for inductive logic suggested
      that examples are easier to process than general principles and are more likely
      to simplify communication. 

PMID- 24667492
TI  - The influence of declining air lead levels on blood lead-air lead slope factors
      in children.
AB  - BACKGROUND: It is difficult to discern the proportion of blood lead (PbB)
      attributable to ambient air lead (PbA), given the multitude of lead (Pb) sources
      and pathways of exposure. The PbB-PbA relationship has previously been evaluated
      across populations. This relationship was a central consideration in the 2008
      review of the Pb national ambient air quality standards. OBJECTIVES: The
      objectives of this study were to evaluate the relationship between PbB and PbA
      concentrations among children nationwide for recent years and to compare the
      relationship with those obtained from other studies in the literature. METHODS:
      We merged participant-level data for PbB from the National Health and Nutrition
      Examination Survey (NHANES) III (1988-1994) and NHANES 9908 (1999-2008) with PbA
      data from the U.S. Environmental Protection Agency. We applied mixed-effects
      models, and we computed slope factor, d[PbB]/d[PbA] or the change in PbB per unit
      change in PbA, from the model results to assess the relationship between PbB and
      PbA. RESULTS: Comparing the NHANES regression results with those from the
      literature shows that slope factor increased with decreasing PbA among children 0
      11 years of age. CONCLUSION: These findings suggest that a larger relative public
      health benefit may be derived among children from decreases in PbA at low PbA
      exposures. Simultaneous declines in Pb from other sources, changes in PbA
      sampling uncertainties over time largely related to changes in the size
      distribution of Pb-bearing particulate matter, and limitations regarding sampling
      size and exposure error may contribute to the variability in slope factor
      observed across peer-reviewed studies.

PMID- 24667494
TI  - Locus coeruleus neuromodulation of memories encoded during negative or unexpected
      action outcomes.
AB  - When people experience surprising or sub-optimal performance outcomes, an
      increase in autonomic arousal helps allocate cognitive resources to adjust
      behavior accordingly. The locus-coeruleus-norepinephrine (LC-NE) system regulates
      a central orienting response to behaviorally relevant events, and might therefore
      signal the need to attend to and learn from performance feedback. Memories of
      such events also rely on elevated NE, suggesting that LC activity not only
      responds to salient performance outcomes but also strengthens memory for stimuli
      associated with their occurrence. In the present study, we used a monetary
      incentive delay paradigm to determine whether LC functional connectivity during
      reaction time feedback relates to trial-by-trial memory of preceding photo
      objects. We used one psychophysiological interaction (PPI) analysis to examine
      patterns of LC functional connectivity that were associated with subsequent
      memory for picture trials in which negative or positive feedback was given, and a
      second PPI analysis to investigate whether successfully encoded objects from
      trials with uncertain outcomes were related to distinct patterns of LC functional
      connectivity across the brain. The PPI results revealed that successfully encoded
      negative feedback trials (i.e., responses exceeding the response deadline) were
      uniquely associated with enhanced functional coupling between the LC and left
      anterior insula. Furthermore, successful memory for objects in low reaction time
      certainty trials (i.e., responses closest to the response deadline) were linked
      to positive LC functional coupling with left dorsolateral prefrontal cortex.
      These findings suggest that noradrenergic influences help facilitate memory
      encoding during outcome processing via dynamic interactions with regions that
      process negative or unexpected feedback. 

PMID- 24667495
TI  - Either the dorsal hippocampus or the dorsolateral striatum is selectively
      involved in consolidation of forced swim-induced immobility depending on genetic
      background.
AB  - Healthy subjects differ in the memory system they engage to learn dual-solution
      tasks. Both genotype and stress experience could contribute to this phenotypic
      variability. The present experiments tested whether the hippocampus and the
      dorsal striatum, the core nodes of two different memory systems, are differently
      involved in 24 h retention of a stress-associated memory in two genetically
      unrelated inbred strains of mice. Mice from both the C57BL/6J and the DBA/2J
      inbred strains showed progressive increase of immobility during 10 min exposure
      to forced swim (FS) and retrieved the acquired levels of immobility when tested
      24h later. The pattern of c-fos immunostaining promoted by FS revealed activation
      of a large number of brain areas in both strains, including CA1 and CA3 fields of
      the hippocampus. However, only DBA/2J mice showed activation of the dorsolateral
      striatum (DLS). In addition, FS induced a positive correlation between c-fos
      expression in the amygdala and CA1 and CA3 in C57BL/6J mice whereas it induced a
      positive correlation between c-fos expression in the amygdala and DLS in DBA/2J
      mice. Finally, temporary post-training inactivation of the dorsal hippocampus, by
      local infusion of lidocaine, prevented 24h retention of immobility in C57BL/6J
      mice only, whereas inactivation of the DLS prevented retention in DBA/2J mice
      only. These findings support the view that genetic factors can determine whether
      the dorsal hippocampus or the DLS are selectively engaged to consolidate stress
      related memory.

PMID- 24667496
TI  - Snake and bird predation drive the repeated convergent evolution of correlated
      life history traits and phenotype in the Izu Island Scincid lizard (Plestiodon
      latiscutatus).
AB  - Predation may create strong natural selection pressure on the phenotype and life
      history characteristics of prey species. The Izu scincid lizards (Plestiodon
      latiscutatus) that inhabit the four Japanese Izu Islands with only bird predators
      are drab brown, mature later, lay small clutches of large eggs, and hatch large
      neonates. In contrast, skinks on seven islands with both snake and bird predators
      are conspicuously colored, mature early, lay large clutches of small eggs, and
      hatch small neonates. We test the hypothesis that these suites of traits have
      evolved independently on each island via natural selection pressures from one of
      two predator regimes--birds-only and birds + snakes. Using two mtDNA genes and a
      nuclear locus, we infer a time-calibrated phylogeny of P. latiscutatus that
      reveals a basal split between Mikura and all islands south, and Miyake, all
      islands north, and the Izu Peninsula. Populations inhabiting Miyake, Niijima,
      Shikine, and Toshima are not monophyletic, suggesting either multiple
      colonizations or an artifact of incomplete lineage sorting (ILS). We therefore
      developed novel phylogenetic comparative analyses that assume either a multiple
      colonization or more restrictive single colonization ILS scenario and found 1)
      statistically significant support for the of different suites of phenotypic and
      life history characteristics with the presence of bird-only or bird + snake
      predator assemblages, and 2) strong phylogenetic support for at least two
      independent derivations of either the "bird-only" or "snakes + birds" phenotypes
      regardless of colonization scenario. Finally, our time-calibrated phylogeographic
      analysis supports the conclusion that the ancestor to modern Izu Island P.
      latiscutatus dispersed from the mainland to the Izu proto-islands between 3-7.6
      million years ago (Ma). These lineages remained present in the area during
      successive formation of the islands, with one lineage re-colonizing the mainland
      0.24-0.7 Ma.

PMID- 24667497
TI  - Viscous pumping inspired by flexible propulsion.
AB  - Fluid-suspended microorganisms have evolved different swimming and feeding
      strategies in order to cope with an environment dominated by viscous effects. For
      instance, ciliated organisms rely on the collective motion of flexible appendages
      to move and feed. By performing a non-reciprocal motion, flexible filaments can
      produce a net propulsive force, or pump fluid, in the absence of inertia.
      Inspired by such a fundamental concept, we propose a strategy to produce
      macroscopic pumping and mixing in creeping flow. We measured experimentally the
      net motion of a Newtonian viscous fluid induced by the reciprocal motion of a
      flapper. When the flapper is rigid no net motion is induced. In contrast, when
      the flapper is made of a flexible material, a net fluid pumping is measured. We
      quantify the effectiveness of this pumping strategy and show that optimal pumping
      is achieved when the length of the flapper is on the same order as the elasto
      hydrodynamic penetration length. We finally discuss the possible applications of
      flexible impellers in mixing operations at low Reynolds numbers. 

PMID- 24667499
TI  - The status of interprofessional education and interprofessional prevention
      education in academic health centers: a national baseline study.
AB  - PURPOSE: Given the emphasis on prevention in U.S. health care reform efforts, the
      importance of interprofessional education (IPE) that prepares health professions
      students to be part of effective health care teams is greater than ever. This
      study examined the prevalence and nature of IPE and interprofessional (IP)
      prevention education in U.S. academic health centers. METHOD: The authors
      extracted a 10-item survey from the longer published IPE Assessment and Planning
      Instrument. In September 2010, they sent the survey to 346 health professions
      leaders in health sciences schools and colleges at 100 academic health centers.
      These institutions were identified via the online membership list of the
      Association of Academic Health Centers. The authors conducted descriptive
      statistical analysis and cross-tabulations. RESULTS: Surveys were completed by
      127 contacts at 68 universities in 31 states and the District of Columbia. IPE
      was more prevalent than IP prevention education in all categories of measurement.
      Respondents affirmed existence of IPE in courses (85.0%) and in clinical
      rotations/internships (80.3%). The majority reported personnel with
      responsibility for IPE (68.5%) or prevention education (59.8%) at their
      institutional unit, and 59.8% reported an IPE office or center. CONCLUSIONS: This
      study provides evidence that IPE and IP prevention education exist in academic
      health centers, but additional attention should be paid to the development of IP
      prevention education. Sample syllabi, job descriptions, and policies may be
      available to support adoption of IPE and IP prevention education. Further effort
      is needed to increase the integration of IP and prevention education into
      practice.

PMID- 24667500
TI  - The use of cognitive task analysis to reveal the instructional limitations of
      experts in the teaching of procedural skills.
AB  - PURPOSE: Because of the automated nature of knowledge, experts tend to omit
      information when describing a task. A potential solution is cognitive task
      analysis (CTA). The authors investigated the percentage of knowledge experts
      omitted when teaching a cricothyrotomy to determine the percentage of additional
      knowledge gained during a CTA interview. METHOD: Three experts were videotaped
      teaching a cricothyrotomy in 2010 at the University of Southern California. After
      transcription, they participated in CTA interviews for the same procedure. Three
      additional surgeons were recruited to perform a CTA for the procedure, and a
      "gold standard" task list was created. Transcriptions from the teaching sessions
      were compared with the task list to identify omitted steps (both "what" and "how"
      to do). Transcripts from the CTA interviews were compared against the task list
      to determine the percentage of knowledge articulated by each expert during the
      initial "free recall" (unprompted) phase of the CTA interview versus the amount
      of knowledge gained by using CTA elicitation techniques (prompted). RESULTS:
      Experts omitted an average of 71% (10/14) of clinical knowledge steps, 51%
      (14/27) of action steps, and 73% (3.6/5) of decision steps. For action steps,
      experts described "how to do it" only 13% (3.6/27) of the time. The average
      number of steps that were described increased from 44% (20/46) when unprompted to
      66% (31/46) when prompted. CONCLUSIONS: This study supports previous research
      that experts unintentionally omit knowledge when describing a procedure. CTA is a
      useful method to extract automated knowledge and augment expert knowledge recall
      during teaching.

PMID- 24667498
TI  - JMJD6 promotes colon carcinogenesis through negative regulation of p53 by
      hydroxylation.
AB  - Jumonji domain-containing 6 (JMJD6) is a member of the Jumonji C domain
      containing family of proteins. Compared to other members of the family, the
      cellular activity of JMJD6 is still not clearly defined and its biological
      function is still largely unexplored. Here we report that JMJD6 is physically
      associated with the tumor suppressor p53. We demonstrated that JMJD6 acts as an
      alpha-ketoglutarate- and Fe(II)-dependent lysyl hydroxylase to catalyze p53
      hydroxylation. We found that p53 indeed exists as a hydroxylated protein in vivo
      and that the hydroxylation occurs mainly on lysine 382 of p53. We showed that
      JMJD6 antagonizes p53 acetylation, promotes the association of p53 with its
      negative regulator MDMX, and represses transcriptional activity of p53. Depletion
      of JMJD6 enhances p53 transcriptional activity, arrests cells in the G1 phase,
      promotes cell apoptosis, and sensitizes cells to DNA damaging agent-induced cell
      death. Importantly, knockdown of JMJD6 represses p53-dependent colon cell
      proliferation and tumorigenesis in vivo, and significantly, the expression of
      JMJD6 is markedly up-regulated in various types of human cancer especially in
      colon cancer, and high nuclear JMJD6 protein is strongly correlated with
      aggressive clinical behaviors of colon adenocarcinomas. Our results reveal a
      novel posttranslational modification for p53 and support the pursuit of JMJD6 as
      a potential biomarker for colon cancer aggressiveness and a potential target for
      colon cancer intervention. 

PMID- 24667501
TI  - Frequency and negative impact of medical student mistreatment based on specialty
      choice: a longitudinal study.
AB  - PURPOSE: According to responses to the Association of American Medical Colleges'
      Medical School Graduation Questionnaire, 17% to 20% of medical students report
      mistreatment. This study examined the longitudinal nature of medical student
      mistreatment based on specialty choice. METHOD: From 2003 to 2010, the authors
      surveyed all medical students at one institution at the end of their third year,
      assessing the frequency and impact of any mistreatment based on specialty choice.
      They analyzed quantitative data on the frequency, impact, sources, and trends
      over time and qualitative data from students' open-ended responses and compared
      data by specialty interest (primary care versus subspecialty). RESULTS: Of the
      1,059 students sent the survey, 801 (76%) responded. Mistreatment based on
      specialty choice was common. The frequency and impact of such mistreatment were
      tightly correlated (Pearson r = 0.8, P < .001). The nature of mistreatment
      differed between students interested in primary care and those interested in a
      subspecialty, occurred more commonly on specific clerkships, and originated most
      often from resident physicians. Students perceived that teaching opportunities
      and evaluations were negatively affected by their specialty choice. An
      association was found between the theme of respect and students reconsidering
      their specialty choice. These patterns of mistreatment were stable over the study
      period, despite several professionalism initiatives. CONCLUSIONS: Mistreatment
      based on specialty choice is a distinct and common phenomenon perpetuated by
      faculty, residents, and peers. More research is needed to explore the potential
      hidden curriculum drivers of these findings and to develop interventions
      specifically targeting this type of mistreatment.

PMID- 24667502
TI  - Anatomy education and classroom versus laparoscopic dissection-based training: a
      randomized study at one medical school.
AB  - PURPOSE: Anatomy education on embalmed specimens is presumed to have added
      educational value. However, although embalmed specimens have been used for
      anatomy education for years, there is little evidence on the added educational
      value of dissection-based teaching. The objective of this randomized study is to
      examine the added value of dissection-based teaching, using models of the
      inguinal region in embalmed specimens. METHOD: In 2011, medical students at
      Erasmus Medical Center, The Netherlands, were randomly assigned to three groups.
      Group I attended lectures, group II attended dissection-based training using
      laparoscopic dissection models, and group III attended lectures as well as
      dissection-based laparoscopic training. To assess the improvement of anatomical
      knowledge, all students had to complete a practical test before, immediately
      after, and two weeks after training. Data were analyzed with mixed modeling.
      RESULTS: Forty-six students participated in this study. No significant difference
      in results was observed among the three groups before the start of training.
      Immediately after the course, groups II and III scored significantly higher than
      group I (P < .001; P < .001), and group II scored higher than group III (P =
      .009). The difference between group I and groups II and III persisted during
      follow-up (P = 012; P = .001). The difference between groups II and III
      disappeared. CONCLUSIONS: Three-dimensional anatomy education with dissection
      models enhances anatomy learning by medical students. Students who received
      dissection-based training scored higher in the short- and long term compared with
      students who did not receive this type of education.

PMID- 24667504
TI  - Milestones of critical thinking: a developmental model for medicine and nursing.
AB  - Critical thinking is essential to a health professional's competence to assess,
      diagnose, and care for patients. Defined as the ability to apply higher-order
      cognitive skills (conceptualization, analysis, evaluation) and the disposition to
      be deliberate about thinking (being open-minded or intellectually honest) that
      lead to action that is logical and appropriate, critical thinking represents a
      "meta-competency" that transcends other knowledge, skills, abilities, and
      behaviors required in health care professions. Despite its importance, the
      developmental stages of critical thinking have not been delineated for nurses and
      physicians. As part of a task force of educators who considered different
      developmental stage theories, the authors have iteratively refined and proposed
      milestones in critical thinking. The attributes associated with unreflective,
      beginning, practicing, advanced, accomplished, and challenged critical thinkers
      are conceived as independent of an individual's level of training. Depending on
      circumstances and environmental factors, even the most experienced clinician may
      demonstrate attributes associated with a challenged thinker. The authors use the
      illustrative case of a patient with abdominal pain to demonstrate how critical
      thinking may manifest in learners at different stages of development, analyzing
      how the learner at each stage applies information obtained in the patient
      interaction to arrive at a differential diagnosis and plan for evaluation. The
      authors share important considerations and provide this work as a foundation for
      the development of effective approaches to teaching and promoting critical
      thinking and to establishing expectations for learners in this essential meta
      competency. 

PMID- 24667503
TI  - The prevalence of medical student mistreatment and its association with burnout.
AB  - PURPOSE: Medical student mistreatment has been recognized for decades and is
      known to adversely impact students personally and professionally. Similarly,
      burnout has been shown to negatively impact students. This study assesses the
      prevalence of student mistreatment across multiple medical schools and
      characterizes the association between mistreatment and burnout. METHOD: In 2011,
      the authors surveyed a nation ally representative sample of third-year medical
      students. Students reported the frequency of experiencing mistreatment by
      attending faculty and residents since the beginning of their clinical rotations.
      Burnout was measured using a validated two-item version of the Maslach Burnout
      Inventory. RESULTS: Of 960 potential respondents from 24 different medical
      schools, 605 (63%) completed the survey, but 41 were excluded because they were
      not currently in their third year of medical school. Of the eligible students,
      the majority reported experiencing at least one incident of mistreatment by
      faculty (64% [361/562]) and by residents (76% [426/562]). A minority of students
      reported experiencing recurrent mistreatment, defined as occurring "several" or
      "numerous" times: 10% [59/562] by faculty and 13% [71/562] by residents.
      Recurrent mistreatment (compared with no or infrequent mistreatment) was
      associated with high burnout: 57% versus 33% (P < .01) for recurrent mistreatment
      by faculty and 49% versus 32% (P < .01) for recurrent mistreatment by residents.
      CONCLUSIONS: Medical student mistreatment remains prevalent. Recurrent
      mistreatment by faculty and residents is associated with medical student burnout.
      Although further investigation is needed to assess causality, these data provide
      impetus for medical schools to address student mistreatment to mitigate its
      adverse consequences.

PMID- 24667505
TI  - Learning about medical student mistreatment from responses to the medical school
      graduation questionnaire.
AB  - Although evidence of medical student mistreatment has accumulated for more than
      20 years, only recently have professional organizations like the Association of
      American Medical Colleges (AAMC) and the American Medical Association truly
      acknowledged it as an issue. Since 1991, the AAMC's annual Medical School
      Graduation Questionnaire (GQ) has included questions about mistreatment.
      Responses to the GQ have become the major source of evidence of the prevalence
      and types of mistreatment. This article reviews national mistreatment data, using
      responses to the GQ from 2000 through 2012; examines how students' experiences
      have changed over time; and highlights the implications of this information for
      the broader medical education system. The authors discuss what mistreatment is,
      including the changing definitions from the GQ; the prevalence, types, and
      sources of mistreatment; and evidence of students reporting incidents. In
      addition, they discuss next steps, including better defining mistreatment,
      specifically public humiliation and belittling, taking into account students'
      subjective evaluations; understanding and addressing the influence of
      institutional culture and what institutions can learn from current approaches at
      other institutions; and developing better systems to report and respond to
      reports of mistreatment. They conclude with a discussion of how mistreatment
      currently is conceptualized within the medical education system and the
      implications of that conceptualization for eradicating mistreatment in the
      future. 

PMID- 24667506
TI  - Achieving balance on the inpatient internal medicine wards: a performance
      improvement project to restructure resident work hours at a tertiary care center.
AB  - PROBLEM: In an era of increasing duty hours restrictions, a growing body of
      literature describes how fatigue and handoffs affect patient care and educational
      experience. Although many studies examine these elements independently, there
      remains little understanding of how they interact. Previously reported
      interventions have yielded unexpected results that are likely dependent on local
      factors. APPROACH: The authors collected data on admissions, emergency department
      disposition, and team continuity during an 8-day period before and a 12-day
      period after changing from a night float system to a resident long-call system
      with a graded transition to a night team. House staff and attendings were
      surveyed afterwards. OUTCOMES: The intervention increased the portion of patients
      admitted to their primary resident from 47% (43/91) to 82% (75/91) (P < .01) and
      improved the percentage of emergency room admissions performed in less than 90
      minutes from 39% (7/18) to 70% (39/44) (P = .02). The percentage of self-reported
      duty hours violations decreased from 55% (16/29) to 6.8% (3/44) (P < .01). Survey
      respondents reported an improved sense of patient involvement, quality of care,
      and handoffs. NEXT STEPS: Designing a call system around a brief assessment of
      admission intensity resulted in better alignment of resident resources with
      workload and improvements in multiple outcomes. Optimization of inpatient work
      structure appears to be significantly affected by local factors. Future trials
      assessing work hour balance will need to take work intensity into account and
      assess a wide variety of potential consequences.

PMID- 24667507
TI  - Defining the key roles and competencies of the clinician-educator of the 21st
      century: a national mixed-methods study.
AB  - PURPOSE: To determine a consensus definition of a clinician-educator and the
      related domains of competence. METHOD: During September 2010 to March 2011, the
      authors conducted a two-phase mixed-methods national study in Canada using (1)
      focus groups of deans of medicine and directors of medical education centers to
      define the attributes, domains of competence, and core competencies of clinician
      educators using a grounded theory analysis, and (2) a survey of 1,130 deans,
      academic chairs, and residency program directors to validate the focus group
      results. RESULTS: The 22 focus group participants described being active in
      clinical practice, applying theory to practice, and engaging in education
      scholarship-but not holding a particular administrative position-as essential
      attributes of clinician-educators. Program directors accounted for 68% of the 350
      survey respondents, academic chairs for 19%, and deans for 13% (response rate:
      31%). Among respondents, 85% endorsed the need for physicians with advanced
      training in medical education to serve as educational consultants. Domains of
      clinician-educator competence endorsed by >85% of respondents as important or
      very important were assessment, communication, curriculum development, education
      theory, leadership, scholarship, and teaching. With regard to training
      requirements, 55% endorsed a master's degree in education as effective
      preparation, whereas 39% considered faculty development programs effective.
      CONCLUSIONS: On the basis of this study's findings, the authors defined a
      clinician-educator as a clinician active in health professional practice who
      applies theory to education practice, engages in education scholarship, and
      serves as a consultant to other health professionals on education issues.

PMID- 24667508
TI  - A tiered quality assurance review process for clinical data management standard
      operating procedures in an academic health center.
AB  - PROBLEM: Standard operating procedures (SOPs) were once considered the province
      of the pharmaceutical industry but are now viewed as a key component of quality
      assurance programs. To address variability and increase the rigor of clinical
      data management (CDM) operations, the Cincinnati Children's Hospital Medical
      Center (CCHMC) decided to create CDM SOPs. APPROACH: In response to this
      challenge, and as part of a broader institutional initiative, the CCHMC
      leadership established an executive steering committee to oversee the development
      and implementation of CDM SOPs. This resulted in the creation of a quality
      assurance review process with three review panels: an SOP development team (16
      clinical data managers and technical staff members), a faculty review panel (8
      senior faculty and administrators), and an expert advisory panel (3 national CDM
      experts). This innovative, tiered review process helped ensure that the new SOPs
      would be created and implemented in accord with good CDM practices and standards.
      OUTCOMES: Twelve fully vetted, institutionally endorsed SOPs and one CDM template
      resulted from the intensive, iterative 10-month process (December 2011 to early
      October 2012). Phased implementation, which incoporated the CDM SOPs into the
      existing audit process for certain types of clinical research studies, was on
      schedule at the time of this writing. NEXT STEPS: Once CCHMC researchers have had
      the opportunity to use the SOPs over time and across a broad range of research
      settings and conditions, the SOPs will be revisited and revalidated.

PMID- 24667509
TI  - Training mentors of clinical and translational research scholars: a randomized
      controlled trial.
AB  - PURPOSE: To determine whether a structured mentoring curriculum improves research
      mentoring skills. METHOD: The authors conducted a randomized controlled trial
      (RCT) at 16 academic health centers (June 2010 to July 2011). Faculty mentors of
      trainees who were conducting clinical/translational research >=50% of the time
      were eligible. The intervention was an eight-hour, case-based curriculum focused
      on six mentoring competencies. The primary outcome was the change in mentors'
      self-reported pretest to posttest composite scores on the Mentoring Competency
      Assessment (MCA). Secondary outcomes included changes in the following: mentors'
      awareness as measured by their self-reported retrospective change in MCA scores,
      mentees' ratings of their mentors' competency as measured by MCA scores, and
      mentoring behaviors as reported by mentors and their mentees. RESULTS: A total of
      283 mentor-mentee pairs were enrolled: 144 mentors were randomized to the
      intervention; 139 to the control condition. Self-reported pre-/posttest change in
      MCA composite scores was higher for mentors in the intervention group compared
      with controls (P < .001). Retrospective changes in MCA composite scores between
      the two groups were even greater, and extended to all six subscale scores (P <
      .001). More intervention-group mentors reported changes in their mentoring
      practices than control mentors (P < .001). Mentees working with intervention
      group mentors reported larger changes in retrospective MCA pre-/posttest scores
      (P = .003) and more changes in their mentors' behavior (P = .002) than those
      paired with control mentors. CONCLUSIONS: This RCT demonstrates that a competency
      based research mentor training program can improve mentors' skills.

PMID- 24667510
TI  - Gender differences in publication productivity, academic position, career
      duration, and funding among U.S. academic radiation oncology faculty.
AB  - PURPOSE: This study aimed to analyze gender differences in rank, career duration,
      publication productivity, and research funding among radiation oncologists at
      U.S. academic institutions. METHOD: For 82 domestic academic radiation oncology
      departments, the authors identified current faculty and recorded their academic
      rank, degree, and gender. The authors recorded bibliographic metrics for
      physician faculty from a commercially available database (Scopus, Elsevier BV),
      including numbers of publications from 1996 to 2012 and h-indices. The authors
      then concatenated these data with National Institutes of Health (NIH) funding per
      Research Portfolio Online Reporting Tools. The authors performed descriptive and
      correlative analyses, stratifying by gender and rank. RESULTS: Of 1,031 faculty,
      293 (28%) women and 738 (72%) men, men had a higher median m-index, 0.58 (range 0
      3.23) versus 0.47 (0-2.5) (P < .05); h-index, 8 (0-59) versus 5 (0-39) (P < .05);
      and publication number, 26 (0-591) versus 13 (0-306) (P < .05). Men were more
      likely to be senior faculty and receive NIH funding. After stratifying for rank,
      these differences were largely nonsignificant. On multivariate analysis, there
      were correlations between gender, career duration and academic position, and h
      index (P < .01). CONCLUSIONS: Determinants of a successful career in academic
      medicine are multifactorial. Data from radiation oncologists show a systematic
      gender association, with fewer women achieving senior faculty rank. However,
      women achieving seniority have productivity metrics comparable to those of male
      counterparts. This suggests that early career development and mentorship of
      female faculty may narrow productivity disparities.

PMID- 24667511
TI  - Variations in senior medical student diagnostic justification ability.
AB  - PURPOSE: To determine the diagnostic justification proficiency of senior medical
      students across a broad spectrum of cases with common chief complaints and
      diagnoses. METHOD: The authors gathered diagnostic justification exercise data
      from the Senior Clinical Comprehensive Examination taken by Southern Illinois
      University School of Medicine's students from the classes of 2011 (n = 67), 2012
      (n = 66), and 2013 (n = 79). After interviewing and examining standardized
      patients, students listed their key findings and diagnostic possibilities
      considered, and provided a written explanation of how they used key findings to
      move from their initial differential diagnoses to their final diagnosis. Two
      physician judges blindly rated responses. RESULTS: Student diagnostic
      justification performance was highly variable from case to case and often rated
      below expectations. Of the students in the classes of 2011, 2012, and 2013, 57%
      (38/67), 23% (15/66), and 33% (26/79) were judged borderline or poor on
      diagnostic justification performance for more than 50% of the cases on the
      examination. CONCLUSIONS: Student diagnostic justification performance was
      inconsistent across the range of cases, common chief complaints, and underlying
      diagnoses used in this study. More than 20% of students exhibited borderline or
      poor diagnostic justification performance on more than 50% of the cases. If these
      results are confirmed in other medical schools, attention needs to be directed to
      investigating new curricular methods that ensure deliberate practice of these
      competencies across the spectrum of common chief complaints and diagnoses and do
      not depend on the available mix of patients.

PMID- 24667512
TI  - Harassment and discrimination in medical training: a systematic review and meta
      analysis.
AB  - PURPOSE: Harassment and discrimination include a wide range of behaviors that
      medical trainees perceive as being humiliating, hostile, or abusive. To
      understand the significance of such mistreatment and to explore potential
      preventive strategies, the authors conducted a systematic review and meta
      analysis to examine the prevalence, risk factors, and sources of harassment and
      discrimination among medical trainees. METHOD: In 2011, the authors identified
      relevant studies by searching MEDLINE and EMBASE, scanning reference lists of
      relevant studies, and contacting experts. They included studies that reported the
      prevalence, risk factors, and sources of harassment and discrimination among
      medical trainees. Two reviewers independently screened all articles and
      abstracted study and participant characteristics and study results. The authors
      assessed the methodological quality in individual studies using the Newcastle
      Ottawa Scale. They also conducted a meta-analysis. RESULTS: The authors included
      57 cross-sectional and 2 cohort studies in their review. The meta-analysis of 51
      studies demonstrated that 59.4% of medical trainees had experienced at least one
      form of harassment or discrimination during their training (95% confidence
      interval [CI]: 52.0%-66.7%). Verbal harassment was the most commonly cited form
      of harassment (prevalence: 63.0%; 95% CI: 54.8%-71.2%). Consultants were the most
      commonly cited source of harassment and discrimination, followed by patients or
      patients' families (34.4% and 21.9%, respectively). CONCLUSIONS: This review
      demonstrates the surprisingly high prevalence of harassment and discrimination
      among medical trainees that has not declined over time. The authors recommend
      both drafting policies and promoting cultural change within academic institutions
      to prevent future abuse.

PMID- 24667513
TI  - Reconceptualizing variable rater assessments as both an educational and clinical
      care problem.
AB  - The public is calling for the U.S. health care and medical education system to be
      accountable for ensuring high-quality, safe, effective, patient-centered care. As
      medical education shifts to a competency-based training paradigm, clinician
      educators' assessment of and feedback to trainees about their developing clinical
      skills becomes paramount. However, there is substantial variability in the
      accuracy, reliability, and validity of the assessments faculty make when they
      directly observe trainees with patients. These difficulties have been treated
      primarily as a rater cognition problem focusing on the inability of the assessor
      to make reliable and valid assessments of the trainee.The authors' purpose is to
      reconceptualize the rater cognition problem as both an educational and clinical
      care problem. The variable quality of faculty assessments is not just a
      psychometric predicament but also an issue that has implications for decisions
      regarding trainee supervision and the delivery of quality patient care. The
      authors suggest that the frame of reference for rating performance during
      workplace-based assessments be the ability to provide safe, effective, patient
      centered care. The authors developed the Accountable Assessment for Quality Care
      and Supervision equation to remind faculty that supervision is a dynamic, complex
      process essential for patients to receive high-quality care. This fundamental
      shift in how assessment is conceptualized requires new models of faculty
      development and emphasizes the essential and irreplaceable importance of the
      clinician educator in trainee assessment. 

PMID- 24667514
TI  - Is poor performance on NBME clinical subject examinations associated with a
      failing score on the USMLE step 3 examination?
AB  - PURPOSE: To investigate the association between poor performance on National
      Board of Medical Examiners clinical subject examinations across six core
      clerkships and performance on the United States Medical Licensing Examination
      Step 3 examination. METHOD: In 2012, the authors studied matriculants from the
      Uniformed Services University of the Health Sciences with available Step 3 scores
      and subject exam scores on all six clerkships (Classes of 2007-2011, N = 654).
      Poor performance on subject exams was defined as scoring one standard deviation
      (SD) or more below the mean using the national norms of the corresponding test
      year. The association between poor performance on the subject exams and the
      probability of passing or failing Step 3 was tested using contingency table
      analyses and logistic regression modeling. RESULTS: Students performing poorly on
      one subject exam were significantly more likely to fail Step 3 (OR 14.23 [95% CI
      1.7-119.3]) compared with students with no subject exam scores that were 1 SD
      below the mean. Poor performance on more than one subject exam further increased
      the chances of failing (OR 33.41 [95% CI 4.4-254.2]). This latter group
      represented 27% of the entire cohort, yet contained 70% of the students who
      failed Step 3. CONCLUSIONS: These findings suggest that individual schools could
      benefit from a review of subject exam performance to develop and validate their
      own criteria for identifying students at risk for failing Step 3.

PMID- 24667516
TI  - Executive onboarding: ensuring the success of the newly hired department chair.
AB  - The success of newly recruited medical school department chairs has become
      increasingly important for achievement of organizational goals. An effective
      onboarding program for these chairs can greatly facilitate early success, as well
      as satisfaction of the new hire with the position and the school. Onboarding
      programs can include traditional orientation items such as payroll signup and
      parking details, but should focus heavily on sharing organizational structure,
      culture, and how things get done. The goals of onboarding will be well served by
      implementation of three roles in the process. An Orientation Navigator can assist
      the new chair in the orientation phase, completing new employee documents and
      navigating the day-to-day challenges of working at the location. A Peer Mentor,
      generally a sitting chair, serves as both "buddy" and mentor, providing moral
      support as well as ensuring that the new chair gains an understanding of the
      people and processes important for getting things done. A Transition Mentor
      serves over a longer term as a sounding board and coach outside the peer group,
      assisting in a variety of ways to promote the chair's growth, development, and
      success as a leader. Finally, any onboarding process is significantly compromised
      without the active participation of the dean, meeting regularly with the chair to
      clarify expectations, promote assimilation, and solve problems. Successful
      onboarding begins with a mindfulness of the needs of the newly hired chair, and a
      well-designed and well-implemented plan will have wide-ranging benefits for the
      chair and the organization. 

PMID- 24667515
TI  - More than a list of values and desired behaviors: a foundational understanding of
      medical professionalism.
AB  - The term "professionalism" has been used in a variety of ways. In 2012, the
      American Board of Medical Specialties (ABMS) Standing Committee on Ethics and
      Professionalism undertook to develop an operational definition of professionalism
      that would speak to the variety of certification and maintenance-of-certification
      activities undertaken by ABMS and its 24 member boards. In the course of this
      work, the authors reviewed prior definitions of professions and professionalism
      and found them to be largely descriptive, or built around lists of proposed
      professional attributes, values, and behaviors. The authors argue that while
      making lists of desirable professional characteristics is necessary and useful
      for teaching and assessment, it is not, by itself, sufficient either to fully
      define professionalism or to capture its social functions. Thus, the authors
      sought to extend earlier work by articulating a definition that explains
      professionalism as the motivating force for an occupational group to come
      together and create, publicly profess, and develop reliable mechanisms to enforce
      shared promises-all with the purpose of ensuring that practitioners are worthy of
      patients' and the public's trust.Using this framework, the authors argue that
      medical professionalism is a normative belief system about how best to organize
      and deliver health care. Believing in professionalism means accepting the premise
      that health professionals must come together to continually define, debate,
      declare, distribute, and enforce the shared competency standards and ethical
      values that govern their work. The authors identify three key implications of
      this new definition for individual clinicians and their professional
      organizations. 

PMID- 24667517
TI  - Publications in academic medical centers: technology-facilitated culture clash.
AB  - Academic culture has a set of norms, expectations, and values that are sometimes
      tacit and sometimes very explicit. In medical school and other health professions
      educational settings, probably the most common norm includes placing a high value
      on peer-reviewed research publications, which are seen as the major evidence of
      scholarly productivity. Other features of academic culture include encouraging
      junior faculty and graduate students to share their research results at
      professional conferences and lecturing with slides as a major way to convey
      information. Major values that faculty share with journal editors include
      responsible conduct of research and proper attribution of others' words and
      ideas. Medical school faculty also value technology and are often quick to
      embrace technological advances that can assist them in their teaching and
      research. This article addresses the effects of technology on three aspects of
      academic culture: education, presentations at professional meetings, and research
      publications.The technologies discussed include online instruction, dissemination
      of conference proceedings on the Internet, plagiarism-detection software, and new
      technologies deployed by the National Center for Biotechnology Information, the
      home of PubMed. The author describes how the ease of deploying new technologies
      without faculty changing their norms and behavior in the areas of teaching and
      research can lead to conflicts of values among key stakeholders in the academic
      medical community, including faculty, journal editors, and professional
      associations. The implications of these conflicts and strategies for managing
      them are discussed. 

PMID- 24667518
TI  - Promoting mentorship in translational research: should we hope for Athena or
      train mentor?
AB  - Despite consensus that mentorship is a critical determinant of career success,
      many academic health centers (AHCs) do not provide formal training for their
      mentors. In part, this problem arises from a lack of evidence-based mentorship
      training curricula. In this issue of Academic Medicine, Pfund and colleagues from
      16 AHCs, including 15 Clinical Translational Science Award institutions report
      the results of a randomized, controlled trial that addressed this research gap.
      In their study, mentors randomized to undertake a formal mentoring curriculum
      reported significant gains in self-assessed competencies. These improvements were
      corroborated by the most critical and objective observers of mentorship skills:
      their own mentees.Evidence-based curricula will not transform research mentorship
      in isolation. An organization-wide culture of mentorship is necessary to meet the
      mentorship needs of all research trainees and faculty. The development of a
      culture of mentorship requires attention to structural issues such as the
      provision of protected time, physical resources, and targeted funding in addition
      to evidence-based curricula. Organizations must monitor the implementation of
      these structures in the day-to-day process of mentorship. Finally, institutions
      must develop measures to track outcomes for both mentors and mentees, and create
      incentives to achieve those outcomes. In the current environment of constrained
      research funding and competing demands from clinical and educational programs, a
      substantive organizational commitment to mentorship is necessary to ensure that
      the next generation of mentees achieves success in translational research. 

PMID- 24667519
TI  - Transcendent professionalism: keeping promises and living the questions.
AB  - Wynia and colleagues propose a definition of professionalism as a belief system
      by which to shape health care rather than a list of values and behaviors. The
      belief that professionalism is the best way to organize and deliver health care
      constitutes a promise to society. The notion that the medical profession as a
      whole as well as its individual members should be held accountable to standards
      of competence, ethical values, and interpersonal attributes developed, declared,
      and enforced by the profession itself is also a promise to society. The author
      argues that good promises offer a stabilizing influence over the inherent
      uncertainty in human relationships and may provide the ground for a lasting
      trustworthy relationship between the medical profession and society; however, the
      professionalism belief system itself is vulnerable if the promise is breached.
      The modern world has challenged the professionalism model of organizing health
      care, and individual practitioners as well as their professional organizations
      are seeking clarity about what professionalism means given current realities.
      This commentary reflects on these circumstances and provides some recommendations
      for developing a construct of professionalism. 

PMID- 24667520
TI  - Controllable fatigue cracking mechanisms of copper bicrystals with a coherent
      twin boundary.
AB  - High-angle grain boundaries are always the preferential fatigue cracking sites,
      while the intrinsic fatigue cracking mechanism of coherent twin boundary remains
      elusive. Here we systematically investigate the fatigue cracking behaviours of
      copper bicrystals with a coherent twin boundary as their sole internal boundary.
      It is found with direct experimental evidence for the first time that, unlike the
      random grain boundaries, the cracking behaviour of the twin boundary strongly
      depends on its orientation with respect to the loading direction. When the twin
      boundary is parallel or perpendicular to the loading direction, the fatigue
      cracks nucleate along the slip bands preferentially; when it is inclined at an
      angle to the loading direction, the fatigue crack is especially apt to nucleate
      along the twin boundary first. The controllable fatigue cracking mechanisms of
      the twin boundary may provide new and important implications for the optimized
      interfacial design of the high-performance materials. 

PMID- 24667521
TI  - An effective filter for IBD detection in large data sets.
AB  - Identity by descent (IBD) inference is the task of computationally detecting
      genomic segments that are shared between individuals by means of common familial
      descent. Accurate IBD detection plays an important role in various genomic
      studies, ranging from mapping disease genes to exploring ancient population
      histories. The majority of recent work in the field has focused on improving the
      accuracy of inference, targeting shorter genomic segments that originate from a
      more ancient common ancestor. The accuracy of these methods, however, is achieved
      at the expense of high computational cost, resulting in a prohibitively long
      running time when applied to large cohorts. To enable the study of large cohorts,
      we introduce SpeeDB, a method that facilitates fast IBD detection in large
      unphased genotype data sets. Given a target individual and a database of
      individuals that potentially share IBD segments with the target, SpeeDB applies
      an efficient opposite-homozygous filter, which excludes chromosomal segments from
      the database that are highly unlikely to be IBD with the corresponding segments
      from the target individual. The remaining segments can then be evaluated by any
      IBD detection method of choice. When examining simulated individuals sharing 4 cM
      IBD regions, SpeeDB filtered out 99.5% of genomic regions from consideration
      while retaining 99% of the true IBD segments. Applying the SpeeDB filter prior to
      detecting IBD in simulated fourth cousins resulted in an overall running time
      that was 10,000x faster than inferring IBD without the filter and retained 99% of
      the true IBD segments in the output. 

PMID- 24667522
TI  - Comparative outcomes of trocar puncture with sump drain, percutaneous drainage,
      and surgical drainage in the management of intra-abdominal abscesses in Crohn's
      disease.
AB  - BACKGROUND: Intra-abdominal abscess is a common complication in Crohn's disease
      (CD). Traditional percutaneous catheter drainage (PCD) and surgical intervention
      could not obtain satisfactory results in some cases. We herein demonstrate a
      novel management option and compare it with traditional strategies. METHODS: A
      total of 77 patients were retrospectively collected into 3 groups. Postoperative
      complication, postoperative recurrence of abscess, subsequent surgery, ultimate
      stoma creation rate, and survival rate were analyzed. RESULTS: Patients were
      divided into the trocar group (n = 21), PCD group (n = 25), and surgery group (n
      = 31). The incidences of postoperative complication as well as the incidence of
      recurrent abscess were lowest in trocar group, and ultimate stoma creation rate
      was highest in the surgery group. Subsequent surgery after initial intervention
      and survival rate during the follow-up period were similar among the 3 groups.
      CONCLUSIONS: Trocar puncture with sump drain had lower incidence of postoperative
      complication, postoperative recurrence of abscess, and ultimate stoma creation
      compared with conventional PCD and surgical interventions. This novel technique
      might be an optimal option in the management of intra-abdominal abscesses in CD.

PMID- 24667523
TI  - The use of time-of-flight camera for navigating robots in computer-aided surgery:
      monitoring the soft tissue envelope of minimally invasive hip approach in a
      cadaver study.
AB  - BACKGROUND: Time-of-flight (TOF) cameras can guide surgical robots or provide
      soft tissue information for augmented reality in the medical field. In this
      study, a method to automatically track the soft tissue envelope of a minimally
      invasive hip approach in a cadaver study is described. METHODS: An algorithm for
      the TOF camera was developed and 30 measurements on 8 surgical situs (direct
      anterior approach) were carried out. The results were compared to a manual
      measurement of the soft tissue envelope. RESULTS: The TOF camera showed an
      overall recognition rate of the soft tissue envelope of 75%. On comparing the
      results from the algorithm with the manual measurements, a significant difference
      was found (P > .005). CONCLUSIONS: In this preliminary study, we have presented a
      method for automatically recognizing the soft tissue envelope of the surgical
      field in a real-time application. Further improvements could result in a robotic
      navigation device for minimally invasive hip surgery.

PMID- 24667524
TI  - Operation of lumbar zygoapophyseal joint cysts using a full-endoscopic
      interlaminar and transforaminal approach: prospective 2-year results of 74
      patients.
AB  - In appropriate situations, extensive decompression with laminectomy often
      continues to be described as the method of choice for operations involving lumbar
      zygoapophyseal joint (z-joint) cysts. Tissue-sparing procedures are nevertheless
      becoming more common. Endoscopic techniques have become the standard procedures
      in many areas because of the advantages they offer in terms of surgical technique
      and in rehabilitation. One key aspect in spinal surgery was the development of
      instruments for sufficient bone resection carried out under continuous visual
      control. This enabled endoscopes to be used when operating on z-joint cysts. The
      objective of this prospective study was to examine the technical possibilities
      for the full-endoscopic interlaminar and transforaminal technique in lumbar z
      joint cysts. A total of 74 patients were followed up for 2 years. The results
      show that 85% of the patients no longer have any leg pain or that the pain had
      been almost completely eliminated, and 11 % experience occasional pain. The
      complication rate was low. The full-endoscopic techniques brought advantages in
      the following areas: operation, complications, traumatization, and
      rehabilitation. The recorded results show that full-endoscopic resection of a z
      joint cyst using an interlaminar and transforaminal approach provides an adequate
      and safe supplement, and is an alternative to conventional procedures when the
      indication criteria are fulfilled. It also offers the advantages of a minimally
      invasive intervention. 

PMID- 24667525
TI  - A comparison between two simulation models for spread of foot-and-mouth disease.
AB  - Two widely used simulation models of foot-and-mouth disease (FMD) were used in
      order to compare the models' predictions in term of disease spread, consequence,
      and the ranking of the applied control strategies, and to discuss the effect of
      the way disease spread is modeled on the predicted outcomes of each model. The
      DTU-DADS (version 0.100), and ISP (version 2.001.11) were used to simulate a
      hypothetical spread of FMD in Denmark. Actual herd type, movements, and location
      data in the period 1st October 2006 and 30th September 2007 was used. The models
      simulated the spread of FMD using 3 different control scenarios: 1) A basic
      scenario representing EU and Danish control strategies, 2) pre-emptive
      depopulation of susceptible herds within a 500 meters radius around the detected
      herds, and 3) suppressive vaccination of susceptible herds within a 1,000 meters
      radius around the detected herds. Depopulation and vaccination started 14 days
      following the detection of the first infected herd. Five thousand index herds
      were selected randomly, of which there were 1,000 cattle herds located in high
      density cattle areas and 1,000 in low density cattle areas, 1,000 swine herds
      located in high density swine areas and 1,000 in low density swine areas, and
      1,000 sheep herds. Generally, DTU-DADS predicted larger, longer duration and
      costlier epidemics than ISP, except when epidemics started in cattle herds
      located in high density cattle areas. ISP supported suppressive vaccination
      rather than pre-emptive depopulation, while DTU-DADS was indifferent to the
      alternative control strategies. Nonetheless, the absolute differences between
      control strategies were small making the choice of control strategy during an
      outbreak to be most likely based on practical reasons. 

PMID- 24667526
TI  - Overexpression of Nrf2 protects against microcystin-induced hepatotoxicity in
      mice.
AB  - Oxidative stress and glutathione (GSH) depletion are implicated in mycocystin
      hepatotoxicity. To investigate the role of nuclear factor erythroid 2-related
      factor 2 (Nrf2) in microcystin-induced liver injury, Nrf2-null, wild-type, and
      Keap1-hepatocyte knockout (Keap1-HKO) mice were treated with microcystin (50
      MUg/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Microcystin
      increased serum alanine aminotransferase and aspartate aminotransferase
      activities, and caused extensive inflammation and necrosis in Nrf2-null and wild
      type mice, but not in Keap1-HKO mice. Oxidative stress and inflammation are
      implicated in microcystin-induced hepatotoxicity, as evidenced by increased lipid
      peroxidation and increased expression of pro-inflammatory genes, such as
      neutrophil-specific chemokines mKC and MIP-2, and pro-inflammatory cytokines IL
      1beta and IL-6. The increased expression of these pro-inflammatory genes was
      attenuated in Keap1-HKO mice. Nrf2 and Nqo1 mRNA and protein were higher in Keap1
      HKO mice at constitutive levels and after microcystin. To further investigate the
      mechanism of the protection, hepatic GSH and the mRNA of GSH-related enzymes were
      determined. Microcystin markedly depleted liver GSH by 60-70% in Nrf2 and WT mice
      but only 35% in Keap1-HKO mice. The mRNAs of GSH conjugation and peroxide
      reduction enzymes, such as Gstalpha1, Gstalpha4, GstMU, and Gpx2 were higher in
      livers of Keap1-HKO mice, together with higher expression of the rate-limiting
      enzyme for GSH synthesis (Gclc). Organic anion transport polypeptides were
      increased by microcystin with the most increase in Keap1-HKO mice. In conclusion,
      this study demonstrates that higher basal levels of Nrf2 and GSH-related genes in
      Keap1-HKO mice prevented microcystin-induced oxidative stress and liver injury. 

PMID- 24667527
TI  - RNA-Seq-based analysis of cold shock response in Thermoanaerobacter
      tengcongensis, a bacterium harboring a single cold shock protein encoding gene.
AB  - BACKGROUND: Although cold shock responses and the roles of cold shock proteins in
      microorganisms containing multiple cold shock protein genes have been well
      characterized, related studies on bacteria possessing a single cold shock protein
      gene have not been reported. Thermoanaerobacter tengcongensis MB4, a thermophile
      harboring only one known cold shock protein gene (TtescpC), can survive from 50
      degrees  to 80  degrees C, but has poor natural competence under cold shock at 50
      degrees C. We therefore examined cold shock responses and their effect on
      natural competence in this bacterium. RESULTS: The transcriptomes of T.
      tengcongensis before and after cold shock were analyzed by RNA-seq and over 1200
      differentially expressed genes were successfully identified. These genes were
      involved in a wide range of biological processes, including modulation of DNA
      replication, recombination, and repair; energy metabolism; production of cold
      shock protein; synthesis of branched amino acids and branched-chain fatty acids;
      and sporulation. RNA-seq analysis also suggested that T. tengcongensis initiates
      cell wall and membrane remodeling processes, flagellar assembly, and sporulation
      in response to low temperature. Expression profiles of TtecspC and failed
      attempts to produce a TtecspC knockout strain confirmed the essential role of
      TteCspC in the cold shock response, and also suggested a role of this protein in
      survival at optimum growth temperature. Repression of genes encoding ComEA and
      ComEC and low energy metabolism levels in cold-shocked cells are the likely basis
      of poor natural competence at low temperature. CONCLUSION: Our study demonstrated
      changes in global gene expression under cold shock and identified several
      candidate genes related to cold shock in T. tengcongensis. At the same time, the
      relationship between cold shock response and poor natural competence at low
      temperature was preliminarily elucidated. These findings provide a foundation for
      future studies on genetic and molecular mechanisms associated with cold shock and
      acclimation at low temperature.

PMID- 24667528
TI  - Evidence for genetic susceptibility to the alcohol dependence syndrome from the
      thiamine transporter 2 gene solute carrier SLC19A3.

PMID- 24667529
TI  - Intraspecific differences in lipid content of calanoid copepods across fine-scale
      depth ranges within the photic layer.
AB  - Copepods are among the most abundant and diverse groups of mesozooplankton in the
      world's oceans. Each species has a certain depth range within which different
      individuals (of the same life stage and sex) are found. Lipids are accumulated in
      many calanoid copepods for energy storage and reproduction. Lipid content in some
      species increases with depth, however studies so far focused mostly on temperate
      and high-latitude seasonal vertically migrating copepods and compared lipid
      contents among individuals either from coarse layers or between diapausing, deep
      dwelling copepods and individuals found in the photic, near-surface layer. Here
      we examined whether lipid contents of individual calanoid copepods of the same
      species, life stage/sex differ between finer depth layers within the upper water
      column of subtropical and Arctic seas. A total of 6 calanoid species were
      collected from samples taken at precise depths within the photic layer in both
      cold eutrophic and warm oligotrophic environments using SCUBA diving, MOCNESS and
      Multinet. Measurements of lipid content were obtained from digitized photographs
      of the collected individuals. The results revealed significant differences in
      lipid content across depth differences as small as 12-15 meters for Mecynocera
      clausi C5 and Ctenocalanus vanus C5 (Red Sea), Clausocalanus furcatus males and
      two clausocalanid C5s (Mediterranean Sea), and Calanus glacialis C5 (Arctic). We
      suggest two possible explanations for the differences in lipid content with depth
      on such a fine scale: predator avoidance and buoyancy. 

PMID- 24667530
TI  - Beau's lines of the fingernails.

PMID- 24667531
TI  - TrueAllele casework on Virginia DNA mixture evidence: computer and manual
      interpretation in 72 reported criminal cases.
AB  - Mixtures are a commonly encountered form of biological evidence that contain DNA
      from two or more contributors. Laboratory analysis of mixtures produces data
      signals that usually cannot be separated into distinct contributor genotypes.
      Computer modeling can resolve the genotypes up to probability, reflecting the
      uncertainty inherent in the data. Human analysts address the problem by
      simplifying the quantitative data in a threshold process that discards
      considerable identification information. Elevated stochastic threshold levels
      potentially discard more information. This study examines three different mixture
      interpretation methods. In 72 criminal cases, 111 genotype comparisons were made
      between 92 mixture items and relevant reference samples. TrueAllele computer
      modeling was done on all the evidence samples, and documented in DNA match
      reports that were provided as evidence for each case. Threshold-based Combined
      Probability of Inclusion (CPI) and stochastically modified CPI (mCPI) analyses
      were performed as well. TrueAllele's identification information in 101 positive
      matches was used to assess the reliability of its modeling approach. Comparison
      was made with 81 CPI and 53 mCPI DNA match statistics that were manually derived
      from the same data. There were statistically significant differences between the
      DNA interpretation methods. TrueAllele gave an average match statistic of 113
      billion, CPI averaged 6.68 million, and mCPI averaged 140. The computer was
      highly specific, with a false positive rate under 0.005%. The modeling approach
      was precise, having a factor of two within-group standard deviation. TrueAllele
      accuracy was indicated by having uniformly distributed match statistics over the
      data set. The computer could make genotype comparisons that were impossible or
      impractical using manual methods. TrueAllele computer interpretation of DNA
      mixture evidence is sensitive, specific, precise, accurate and more informative
      than manual interpretation alternatives. It can determine DNA match statistics
      when threshold-based methods cannot. Improved forensic science computation can
      affect criminal cases by providing reliable scientific evidence. 

PMID- 24667532
TI  - Demographic and clinical predictors of mortality from highly pathogenic avian
      influenza A (H5N1) virus infection: CART analysis of international cases.
AB  - BACKGROUND: Human infections with highly pathogenic avian influenza (HPAI) A
      (H5N1) viruses have occurred in 15 countries, with high mortality to date.
      Determining risk factors for morbidity and mortality from HPAI H5N1 can inform
      preventive and therapeutic interventions. METHODS: We included all cases of human
      HPAI H5N1 reported in World Health Organization Global Alert and Response updates
      and those identified through a systematic search of multiple databases (PubMed,
      Scopus, and Google Scholar), including articles in all languages. We abstracted
      predefined clinical and demographic predictors and mortality and used bivariate
      logistic regression analyses to examine the relationship of each candidate
      predictor with mortality. We developed and pruned a decision tree using
      nonparametric Classification and Regression Tree methods to create risk strata
      for mortality. FINDINGS: We identified 617 human cases of HPAI H5N1 occurring
      between December 1997 and April 2013. The median age of subjects was 18 years
      (interquartile range 6-29 years) and 54% were female. HPAI H5N1 case-fatality
      proportion was 59%. The final decision tree for mortality included age, country,
      per capita government health expenditure, and delay from symptom onset to
      hospitalization, with an area under the receiver operator characteristic (ROC)
      curve of 0.81 (95% CI: 0.76-0.86). INTERPRETATION: A model defined by four
      clinical and demographic predictors successfully estimated the probability of
      mortality from HPAI H5N1 illness. These parameters highlight the importance of
      early diagnosis and treatment and may enable early, targeted pharmaceutical
      therapy and supportive care for symptomatic patients with HPAI H5N1 virus
      infection.

PMID- 24667533
TI  - Genetic diversity and distribution patterns of host insects of Caterpillar Fungus
      Ophiocordyceps sinensis in the Qinghai-Tibet Plateau.
AB  - The caterpillar fungus Ophiocordyceps sinensis is one of the most valuable
      medicinal fungi in the world, and it requires host insects in family Hepialidae
      (Lepidoptera) to complete its life cycle. However, the genetic diversity and
      phylogeographic structures of the host insects remain to be explored. We analyzed
      the genetic diversity and temporal and spatial distribution patterns of genetic
      variation of the host insects throughout the O. sinensis distribution. Abundant
      haplotype and nucleotide diversity mainly existed in the areas of Nyingchi,
      ShangriLa, and around the edge of the Qinghai-Tibet Plateau, where are considered
      as the diversity center or micro-refuges of the host insects of O. sinensis.
      However, there was little genetic variation among host insects from 72.1% of all
      populations, indicating that the host species composition might be relatively
      simple in large-scale O. sinensis populations. All host insects are monophyletic
      except for those from four O. sinensis populations around Qinghai Lake.
      Significant phylogeographic structure (NST>GST, P<0.05) was revealed for the
      monophyletic host insects, and the three major phylogenetic groups corresponded
      with specific geographical areas. The divergence of most host insects was
      estimated to have occurred at ca. 3.7 Ma, shortly before the rapid uplift of the
      QTP. The geographical distribution and star-like network of the haplotypes
      implied that most host insects were derived from the relicts of a once-widespread
      host that subsequently became fragmented. Neutrality tests, mismatch distribution
      analysis, and expansion time estimation confirmed that most host insects
      presented recent demographic expansions that began ca. 0.118 Ma in the late
      Pleistocene. Therefore, the genetic diversity and distribution of the present-day
      insects should be attributed to effects of the Qinghai-Tibet Plateau uplift and
      glacial advance/retreat cycles during the Quaternary ice age. These results
      provide valuable information to guide the protection and sustainable use of these
      host insects as well as O. sinensis. 

PMID- 24667534
TI  - Effect of S-adenosyl-L-methionine (SAM), an allosteric activator of cystathionine
      beta-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in
      vitro.
AB  - Recent data show that colon cancer cells selectively overexpress cystathionine
      beta-synthase (CBS), which produces hydrogen sulfide (H2S), to maintain cellular
      bioenergetics, support tumor growth and stimulate angiogenesis and vasorelaxation
      in the tumor microenvironment. The purpose of the current study was to
      investigate the effect of the allosteric CBS activator S-adenosyl-L-methionine
      (SAM) on the proliferation and bioenergetics of the CBS-expressing colon cancer
      cell line HCT116. The non-transformed, non-tumorigenic colon epithelial cell line
      NCM356 was used as control. For assessment of cell proliferation, the xCELLigence
      system was used. Bioenergetic function was measured by Extracellular Flux
      Analysis. Experiments using human recombinant CBS or HCT116 homogenates
      complemented the cell-based studies. SAM markedly enhanced CBS-mediated H2S
      production in vitro, especially when a combination of cysteine and homocysteine
      was used as substrates. Addition of SAM (0.1-3 mM) to HCT116 cells induced a
      concentration-dependent increase H2S production. SAM exerted time- and
      concentration-dependent modulatory effects on cell proliferation. At 0.1-1 mM SAM
      increased HCT116 proliferation between 0 and 12 h, while the highest SAM
      concentration (3 mM) inhibited proliferation. Over a longer time period (12-24
      h), only the lowest concentration of SAM used (0.1 mM) stimulated cell
      proliferation; higher SAM concentrations produced a concentration-dependent
      inhibition. The short-term stimulatory effects of SAM were attenuated by the CBS
      inhibitor aminooxyacetic acid (AOAA) or by stable silencing of CBS. In contrast,
      the inhibitory effects of SAM on cell proliferation was unaffected by CBS
      inhibition or CBS silencing. In contrast to HCT116 cells, the lower rate of
      proliferation of the low-CBS expressor NCM356 cells was unaffected by SAM. Short
      term (1 h) exposure of HCT116 cells to SAM induced a concentration-dependent
      increase in oxygen consumption and bioenergetic function at 0.1-1 mM, while 3 mM
      was inhibitory. Longer-term (72 h) exposure of HCT116 cells to all concentrations
      of SAM tested suppressed mitochondrial oxygen consumption rate, cellular ATP
      content and cell viability. The stimulatory effect of SAM on bioenergetics was
      attenuated in cells with stable CBS silencing, while the inhibitory effects were
      unaffected. In NCM356 cells SAM exerted smaller effects on cellular bioenergetics
      than in HCT116 cells. We have also observed a downregulation of CBS in response
      to prolonged exposure of SAM both in HCT116 and NCM356 cells. Taken together, the
      results demonstrate that H2S production in HCT116 cells is stimulated by the
      allosteric CBS activator, SAM. At low-to intermediate levels and early time
      periods the resulting H2S serves as an endogenous cancer cell growth and
      bioenergetic factor. In contrast, the inhibition of cell proliferation and
      bioenergetic function by SAM does not appear to relate to adverse autocrine
      effects of H2S resulting from CBS over-stimulation but, rather to CBS-independent
      pharmacological effects.

PMID- 24667535
TI  - Controlled exposures to air pollutants and risk of cardiac arrhythmia.
AB  - BACKGROUND: Epidemiological studies have reported associations between air
      pollution exposure and increases in cardiovascular morbidity and mortality.
      Exposure to air pollutants can influence cardiac autonomic tone and reduce heart
      rate variability, and may increase the risk of cardiac arrhythmias, particularly
      in susceptible patient groups. OBJECTIVES: We investigated the incidence of
      cardiac arrhythmias during and after controlled exposure to air pollutants in
      healthy volunteers and patients with coronary heart disease. METHODS: We analyzed
      data from 13 double-blind randomized crossover studies including 282 participants
      (140 healthy volunteers and 142 patients with stable coronary heart disease) from
      whom continuous electrocardiograms were available. The incidence of cardiac
      arrhythmias was recorded for each exposure and study population. RESULTS: There
      were no increases in any cardiac arrhythmia during or after exposure to dilute
      diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered
      carbon nanoparticles, or high ambient levels of air pollution in either healthy
      volunteers or patients with coronary heart disease. CONCLUSIONS: Acute controlled
      exposure to air pollutants did not increase the short-term risk of arrhythmia in
      participants. Research employing these techniques remains crucial in identifying
      the important pathophysiological pathways involved in the adverse effects of air
      pollution, and is vital to inform environmental and public health policy
      decisions.

PMID- 24667536
TI  - Two enhancers control transcription of Drosophila muscleblind in the embryonic
      somatic musculature and in the central nervous system.
AB  - The phylogenetically conserved family of Muscleblind proteins are RNA-binding
      factors involved in a variety of gene expression processes including alternative
      splicing regulation, RNA stability and subcellular localization, and miRNA
      biogenesis, which typically contribute to cell-type specific differentiation. In
      humans, sequestration of Muscleblind-like proteins MBNL1 and MBNL2 has been
      implicated in degenerative disorders, particularly expansion diseases such as
      myotonic dystrophy type 1 and 2. Drosophila muscleblind was previously shown to
      be expressed in embryonic somatic and visceral muscle subtypes, and in the
      central nervous system, and to depend on Mef2 for transcriptional activation.
      Genomic approaches have pointed out candidate gene promoters and tissue-specific
      enhancers, but experimental confirmation of their regulatory roles was lacking.
      In our study, luciferase reporter assays in S2 cells confirmed that regions P1
      (515 bp) and P2 (573 bp), involving the beginning of exon 1 and exon 2,
      respectively, were able to initiate RNA transcription. Similarly, transgenic
      Drosophila embryos carrying enhancer reporter constructs supported the existence
      of two regulatory regions which control embryonic expression of muscleblind in
      the central nerve cord (NE, neural enhancer; 830 bp) and somatic (skeletal)
      musculature (ME, muscle enhancer; 3.3 kb). Both NE and ME were able to boost
      expression from the Hsp70 heterologous promoter. In S2 cell assays most of the ME
      enhancer activation could be further narrowed down to a 1200 bp subregion (ME.3),
      which contains predicted binding sites for the Mef2 transcription factor. The
      present study constitutes the first characterization of muscleblind enhancers and
      will contribute to a deeper understanding of the transcriptional regulation of
      the gene. 

PMID- 24667538
TI  - Thermodynamic investigation of Z33-antibody interaction leads to selective
      purification of human antibodies.
AB  - Antibodies, such as IgGs, are widely applied as detection probes, purification
      ligands and targeting moieties in research and medicine. Protein A from
      Staphylococcus aureus is capable of selectively binding to antibodies. Z33, a 33
      amino acid peptide sequence derived from Protein A, is a minimized binding domain
      with comparable interaction potential. This peptide was fused to two different
      proteins without perturbing the properties of both the protein and the Z33
      domain. The thermodynamic parameters for the interaction of the fusion proteins
      with antibodies from various species were determined by isothermal titration
      calorimetry. This showed that binding was enthalpically driven and entropically
      unfavorable. A difference in Z33 binding affinity of several orders of magnitude
      was observed between human and bovine antibodies. This selectivity toward human
      IgGs was utilized for the efficient and selective purification of human IgGs from
      mixtures containing bovine IgGs and other proteins by affinity precipitation
      employing a fusion protein of Z33 and a stimulus-responsive elastin-like
      polypeptide. 

PMID- 24667537
TI  - Coronin 1 regulates cognition and behavior through modulation of cAMP/protein
      kinase A signaling.
AB  - Cognitive and behavioral disorders are thought to be a result of neuronal
      dysfunction, but the underlying molecular defects remain largely unknown. An
      important signaling pathway involved in the regulation of neuronal function is
      the cyclic AMP/Protein kinase A pathway. We here show an essential role for
      coronin 1, which is encoded in a genomic region associated with neurobehavioral
      dysfunction, in the modulation of cyclic AMP/PKA signaling. We found that coronin
      1 is specifically expressed in excitatory but not inhibitory neurons and that
      coronin 1 deficiency results in loss of excitatory synapses and severe
      neurobehavioral disabilities, including reduced anxiety, social deficits,
      increased aggression, and learning defects. Electrophysiological analysis of
      excitatory synaptic transmission in amygdala revealed that coronin 1 was
      essential for cyclic-AMP-protein kinase A-dependent presynaptic plasticity. We
      further show that upon cell surface stimulation, coronin 1 interacted with the G
      protein subtype Galphas to stimulate the cAMP/PKA pathway. The absence of coronin
      1 or expression of coronin 1 mutants unable to interact with Galphas resulted in
      a marked reduction in cAMP signaling. Strikingly, synaptic plasticity and
      behavioral defects of coronin 1-deficient mice were restored by in vivo infusion
      of a membrane-permeable cAMP analogue. Together these results identify coronin 1
      as being important for cognition and behavior through its activity in promoting
      cAMP/PKA-dependent synaptic plasticity and may open novel avenues for the
      dissection of signal transduction pathways involved in neurobehavioral processes.

PMID- 24667539
TI  - 13 C-metabolic flux analysis in heterologous cellulase production by Bacillus
      subtilis genome-reduced strain.
AB  - The great potential of Bacillus subtilis to produce biomaterials would be further
      enhanced by the development of strains with deletions of non-essential genomic
      regions. Here, using stationary (13)C-metabolic flux analysis ((13)C-MFA), we
      investigated the metabolism during cellulase production by the genome-reduced B.
      subtilis strain MGB874. We transformed MGB874 and wild-type strains with the
      heterologous cellulase gene, and cultured these on a synthetic medium containing
      glucose as carbon source. The addition of glutamate and the genome reduction
      enhanced cellulase production, which led us to use (13)C-MFA to assess the
      effects of glutamate addition and gene deletions on metabolism. We found that
      there was a significant increase in the flux in the pentose phosphate (PP)
      pathway, whereas the fluxes of reactions from acetyl-CoA to alpha-ketoglutarate
      were repressed in the presence of glutamate. We hypothesize that the increase in
      the PP pathway flux was caused by the decrease of citrate synthase flux through
      the accumulation of glycolytic intermediates. Excess NADPH produced by the PP
      pathway may affect the increase in cellulase production. Furthermore, the fluxes
      on glycolysis and the acetate formation of the cellulase-producing wild-type
      strain were significantly larger than that of the cellulase-producing MGB874
      strain when the strains were cultured with glucose and glutamate. 

PMID- 24667540
TI  - Microarray-based screening of heat shock protein inhibitors.
AB  - Based on the importance of heat shock proteins (HSPs) in diseases such as cancer,
      Alzheimer's disease or malaria, inhibitors of these chaperons are needed. Today's
      state-of-the-art techniques to identify HSP inhibitors are performed in
      microplate format, requiring large amounts of proteins and potential inhibitors.
      In contrast, we have developed a miniaturized protein microarray-based assay to
      identify novel inhibitors, allowing analysis with 300 pmol of protein. The assay
      is based on competitive binding of fluorescence-labeled ATP and potential
      inhibitors to the ATP-binding site of HSP. Therefore, the developed microarray
      enables the parallel analysis of different ATP-binding proteins on a single
      microarray. We have demonstrated the possibility of multiplexing by immobilizing
      full-length human HSP90alpha and HtpG of Helicobacter pylori on microarrays.
      Fluorescence-labeled ATP was competed by novel geldanamycin/reblastatin
      derivatives with IC50 values in the range of 0.5 nM to 4 MUM and Z(*)-factors
      between 0.60 and 0.96. Our results demonstrate the potential of a target-oriented
      multiplexed protein microarray to identify novel inhibitors for different members
      of the HSP90 family.

PMID- 24667542
TI  - Flexible propulsors in ground effect.
AB  - We present experimental evidence for the hydrodynamic benefits of swimming 'in
      ground effect', that is, near a solid boundary. This situation is common to fish
      that swim near the substrate, especially those that are dorsoventrally
      compressed, such as batoids and flatfishes. To investigate flexible propulsors in
      ground effect, we conduct force measurements and particle image velocimetry on
      flexible rectangular panels actuated at their leading edge near the wall of a
      water channel. For a given actuation mode, the panels swim faster near the
      channel wall while maintaining the same propulsive economy. In conditions
      producing net thrust, panels produce more thrust near the ground. When operating
      in resonance, swimming near the ground can also increase propulsive efficiency.
      Finally, the ground can act to suppress three-dimensional modes, thereby
      increasing thrust and propulsive efficiency. The planform considered here is non
      biological, but the hydrodynamic benefits are likely to apply to more complex
      geometries, especially those where broad flexible propulsors are involved such as
      fish bodies and fins. Such fish could produce more thrust by swimming near the
      ground, and in some cases do so more efficiently. 

PMID- 24667543
TI  - Influence of 20-year organic and inorganic fertilization on organic carbon
      accumulation and microbial community structure of aggregates in an intensively
      cultivated sandy loam soil.
AB  - To evaluate the long-term effect of compost (CM) and inorganic fertilizer (NPK)
      application on microbial community structure and organic carbon (OC) accumulation
      at aggregate scale, soils from plots amended with CM, NPK and no fertilizer
      (control) for 20 years (1989-2009) were collected. Soil was separated into large
      macroaggregate (>2,000 MUm), small macroaggregate (250-2,000 MUm), microaggregate
      (53-250 MUm), silt (2-53 MUm) and clay fraction (<2 MUm) by wet-sieving, and
      their OC concentration and phospholipid fatty acids (PLFA) were measured. The 20
      year application of compost significantly (P<0.05) increased OC by 123-134% and
      accelerated the formation of macroaggregates, but decreased soil oxygen diffusion
      coefficient. NPK mainly increased OC in macroaggregates and displayed weaker
      influence on aggregation. Bacteria distributed in all aggregates, while fungi and
      actinobacteria were mainly in macroaggregates and microaggregates. The ratio of
      monounsaturated to branched (M/B) PLFAs, as an indicator for the ratio of aerobic
      to anaerobic microorganisms, increased inversely with aggregate size. Both NPK
      and especially CM significantly (P<0.05) decreased M/B ratios in all aggregates
      except the silt fraction compared with the control. The increased organic C in
      aggregates significantly (P<0.05) negatively correlated with M/B ratios under CM
      and NPK. Our study suggested that more efficient OC accumulations in aggregates
      under CM-treated than under NPK-treated soil was not only due to a more effective
      decrease of actinobacteria, but also a decrease of monounsaturated PLFAs and an
      increase of branched PLFAs. Aggregations under CM appear to alter micro-habitats
      to those more suitable for anaerobes, which in turn boosts OC accumulation. 

PMID- 24667541
TI  - Platelet serotonin transporter function predicts default-mode network activity.
AB  - BACKGROUND: The serotonin transporter (5-HTT) is abundantly expressed in humans
      by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from
      extracellular space. A blood-brain relationship between platelet and synaptosomal
      5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT
      uptake can predict neural activation of human brain networks that are known to be
      under serotonergic influence. METHODS: A functional magnetic resonance study was
      performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was
      assessed in blood platelets. We used a mixed-effects multilevel analysis
      technique (MEMA) to test for linear relationships between whole-brain, blood
      oxygen-level dependent (BOLD) activity and platelet Vmax. RESULTS: The present
      study demonstrates that increases in platelet Vmax significantly predict default
      mode network (DMN) suppression in healthy subjects independent of genetic
      variation within SLC6A4. Furthermore, functional connectivity analyses indicate
      that platelet Vmax is related to global DMN activation and not intrinsic DMN
      connectivity. CONCLUSION: This study provides evidence that platelet Vmax
      predicts global DMN activation changes in healthy subjects. Given previous
      reports on platelet-synaptosomal Vmax coupling, results further suggest an
      important role of neuronal 5-HT reuptake in DMN regulation.

PMID- 24667544
TI  - Spontaneous tumour regression in keratoacanthomas is driven by Wnt/retinoic acid
      signalling cross-talk.
AB  - A fundamental goal in cancer biology is to identify the cells and signalling
      pathways that are keys to induce tumour regression. Here we use a spontaneously
      self-regressing tumour, cutaneous keratoacanthoma (KAs), to identify
      physiological mechanisms that drive tumour regression. By using a mouse model
      system that recapitulates the behaviour of human KAs, we show that self
      regressing tumours shift their balance to a differentiation programme during
      regression. Furthermore, we demonstrate that developmental programs utilized for
      skin hair follicle regeneration, such as Wnt, are hijacked to sustain tumour
      growth and that the retinoic acid (RA) signalling pathway promotes tumour
      regression by inhibiting Wnt signalling. Finally, we find that RA signalling can
      induce regression of malignant tumours that do not normally spontaneously
      regress, such as squamous cell carcinomas. These findings provide new insights
      into the physiological mechanisms of tumour regression and suggest therapeutic
      strategies to induce tumour regression. 

PMID- 24667545
TI  - Characterisation of FUT4 and FUT6 alpha-(1 -> 2)-fucosyltransferases reveals that
      absence of root arabinogalactan fucosylation increases Arabidopsis root growth
      salt sensitivity.
AB  - Plant type II arabinogalactan (AG) polysaccharides are attached to
      arabinogalactan proteins (AGPs) at hydroxyproline residues, and they are very
      diverse and heterogeneous structures. The AG consists of a beta-(1 -> 3)-linked
      galactan backbone with beta-(1 -> 6)-galactan side chains that are modified
      mainly with arabinose, but they may also contain glucuronic acid, rhamnose or
      other sugars. Here, we studied the positions of fucose substitutions in AGPs, and
      we investigated the functions of this fucosylation. Monosaccharide analysis of
      Arabidopsis leaf AGP extracts revealed a significant reduction in L-Fucose
      content in the fut4 mutant, but not in the fut6 mutant. In addition, Fucose was
      reduced in the fut4 mutant in root AGP extracts and was absent in the fut4/fut6
      mutant. Curiously, in all cases reduction of fucose was accompanied with a
      reduction in xylose levels. The fucosylated AGP structures in leaves and roots in
      wild type and fut mutant plants were characterised by sequential digestion with
      AG specific enzymes, analysis by Polysaccharide Analysis using Carbohydrate gel
      Electrophoresis, and Matrix Assisted Laser Desorption/Ionisation (MALDI)-Time of
      Flight Mass spectrometry (MS). We found that FUT4 is solely responsible for the
      fucosylation of AGPs in leaves. The Arabidopsis thaliana FUT4 and FUT6 genes have
      been previously proposed to be non-redundant AG-specific fucosyltransferases.
      Unexpectedly, FUT4 and FUT6 enzymes both fucosylate the same AGP structures in
      roots, suggesting partial redundancy to each other. Detailed structural
      characterisation of root AGPs with high energy MALDI-Collision Induced
      Dissociation MS and NMR revealed an abundant unique AG oligosaccharide structure
      consisting of terminal xylose attached to fucose. The loss of this structure in
      fut4/fut6 mutants explains the reduction of both fucose and xylose in AGP
      extracts. Under salt-stress growth conditions the fut4/fut6 mutant lacking AGP
      fucosylation exhibited a shorter root phenotype than wild type plants,
      implicating fucosylation of AGPs in maintaining proper cell expansion under these
      conditions.

PMID- 24667548
TI  - Temporal profile of the renal transcriptome of HIV-1 transgenic mice during
      disease progression.
AB  - Profiling of temporal changes of gene expression in the same kidney over the
      course of renal disease progression is challenging because repeat renal biopsies
      are rarely indicated in clinical practice. Here, we profiled the temporal change
      in renal transcriptome of HIV-1 transgenic mice (Tg26), an animal model for human
      HIV-associated nephropathy (HIVAN), and their littermates at three different time
      points (4, 8, and 12 weeks of age) representing early, middle, and late stages of
      renal disease by serial kidney biopsy. We analyzed both static levels of gene
      expression at three stages of disease and dynamic changes in gene expression
      between different stages. Analysis of static and dynamic changes in gene
      expression revealed that up-regulated genes at the early and middle stages are
      mostly involved in immune response and inflammation, whereas down-regulated genes
      mostly related to fatty acid and retinoid metabolisms. We validated the
      expression of a selected panel of genes that are up-regulated at the early stage
      (CCL2, CCL5, CXCL11, Ubd, Anxa1, and Spon1) by real-time PCR. Among these up
      regulated genes, Spon1, which is a previously identified candidate gene for
      hypertension, was found to be up-regulated in kidney of human with diabetic
      nephropathy. Immunostaining of human biopsy samples demonstrated that protein
      expression of Spon1 was also markedly increased in kidneys of patients with both
      early and late HIVAN and diabetic nephropathy. Our studies suggest that analysis
      of both static and dynamic changes of gene expression profiles in disease
      progression avails another layer of information that could be utilized to gain a
      more comprehensive understanding of disease progression and identify potential
      biomarkers and drug targets. 

PMID- 24667547
TI  - Effects of duloxetine and WAY100635 on pudendal inhibition of bladder
      overactivity in cats.
AB  - This study was aimed at determining the effect of duloxetine (a serotonin
      norepinephrine reuptake inhibitor) on pudendal inhibition of bladder
      overactivity. Cystometrograms were performed on 15 cats under alpha-chloralose
      anesthesia by infusing saline and then 0.25% acetic acid (AA) to induce bladder
      overactivity. To inhibit bladder overactivity, pudendal nerve stimulation (PNS)
      at 5 Hz was applied to the right pudendal nerve at two and four times the
      threshold (T) intensity for inducing anal twitch. Duloxetine (0.03-3 mg/kg) was
      administered intravenously to determine the effect on PNS inhibition. AA
      irritation significantly (P < 0.01) reduced bladder capacity to 27.9 +/- 4.6% of
      saline control capacity. PNS alone at both 2T and 4T significantly (P < 0.01)
      inhibited bladder overactivity and increased bladder capacity to 83.6 +/- 7.6%
      and 87.5 +/- 7.7% of saline control, respectively. Duloxetine at low doses (0.03
      0.3 mg/kg) caused a significant reduction in PNS inhibition without changing
      bladder capacity. However, at high doses (1-3 mg/kg) duloxetine significantly
      increased bladder capacity but still failed to enhance PNS inhibition. WAY100635
      (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridyl)cyclohexanecarboxamide; a 5-HT1A receptor antagonist, 0.5-1 mg/kg i.v.)
      reversed the suppressive effect of duloxetine on PNS inhibition and significantly
      (P < 0.05) increased the inhibitory effect of duloxetine on bladder overactivity
      but did not enhance the effect of PNS. These results indicate that activation of
      5-HT1A autoreceptors on the serotonergic neurons in the raphe nucleus may
      suppress duloxetine and PNS inhibition, suggesting that the coadministration of a
      5-HT1A antagonist drug might be useful in enhancing the efficacy of duloxetine
      alone and/or the additive effect of PNS-duloxetine combination for the treatment
      of overactive bladder symptoms. 

PMID- 24667549
TI  - Systemic safety of ranibizumab for diabetic macular edema: meta-analysis of
      randomized trials.
AB  - PURPOSE: To evaluate systemic safety of ranibizumab for diabetic macular edema.
      METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and
      ClinicalTrials.gov were systematically reviewed. Eligible studies were randomized
      trials on ranibizumab for diabetic macular edema with observation at least 6
      months and >=80% completion rate that reported systemic adverse events of
      cerebrovascular accident, myocardial infarction, vascular death, and overall
      mortality. The numbers of adverse events were compared between patients treated
      with ranibizumab and those without. Furthermore, dose-dependent effect of
      ranibizumab was estimated for overall mortality through Poisson meta-regression.
      RESULTS: Six trials with 2,459 patients were included. All trials had exclusion
      criteria on systemic vascular conditions for enrollment. Risk ratio for
      cerebrovascular accident, myocardial infarction, vascular death, and overall
      mortality were 0.80 (95% confidence interval, 0.37-1.73; P = 0.57), 0.91 (95%
      confidence interval, 0.46-1.80; P = 0.78), 1.29 (95% confidence interval, 0.58
      2.86; P = 0.53), and 1.92 (95% confidence interval, 0.78-4.73; P = 0.16),
      respectively. Poisson regression model showed a significant dose-dependent
      increase in overall mortality in the largest randomized trial using monthly
      ranibizumab (P = 0.04). However, the significance disappeared (P = 0.133) when
      pooled with other studies using ranibizumab on pro re nata basis. CONCLUSION:
      Ranibizumab for diabetic macular edema is considered safe when the patients are
      carefully selected based on systemic vascular conditions and it is used on pro re
      nata basis. Further evaluation is necessary on more intensive use or on high-risk
      patients.

PMID- 24667550
TI  - Bimanual intraocular lens rescue with transconjunctival scleral fixation.

PMID- 24667557
TI  - Thermoregulatory development and behavior of Ctenomys talarum pups during brief
      repeated postnatal isolation.
AB  - In altricial mammals, the role of the mother and siblings throughout pup's early
      ontogeny is critical to determine "normal" development in neonates. It has been
      reported that variations in parental investment during pups' development affect
      thermoregulatory capacity, growth patterns, brain development and behavior during
      lifetime, such as spatial learning and memory in adults. Ctenomys talarum (tuco
      tuco) is a solitary subterranean rodent, who inhabits complex burrows and
      exhibits developed spatial orientation abilities. Tuco-tuco's pups display an
      altricial development, spending more than 80% of the time in contact with the
      mother. Throughout weaning period, pups display active exploratory behavior and
      improvements in their spatial capabilities. Then, we determined the effect of
      repeated brief postnatal isolations on the acquisition of physiological
      thermoregulation and the development of spatial learning capabilities in tuco
      tuco's pups. As it occurs in wild animals, daily brief isolations (30min) did not
      affect the acquisition of adult's body temperature nor resting metabolic rate's
      development pattern. Moreover, behavioral response and adult spatial abilities of
      isolated pups were similar to that observed in non-isolated ones. Then, during
      periods of mother's absence, minor physiological and behavioral adjustments, such
      as shivering and postural changes, are required to keep C. talarum pups within
      allostasis.

PMID- 24667558
TI  - Carotenoid-based coloration in cichlid fishes.
AB  - Animal colors play important roles in communication, ecological interactions and
      speciation. Carotenoid pigments are responsible for many yellow, orange and red
      hues in animals. Whereas extensive knowledge on the proximate mechanisms
      underlying carotenoid coloration in birds has led to testable hypotheses on avian
      color evolution and signaling, much less is known about the expression of
      carotenoid coloration in fishes. Here, we promote cichlid fishes (Perciformes:
      Cichlidae) as a system in which to study the physiological and evolutionary
      significance of carotenoids. Cichlids include some of the best examples of
      adaptive radiation and color pattern diversification in vertebrates. In this
      paper, we examine fitness correlates of carotenoid pigmentation in cichlids and
      review hypotheses regarding the signal content of carotenoid-based ornaments.
      Carotenoid-based coloration is influenced by diet and body condition and is
      positively related to mating success and social dominance. Gaps in our knowledge
      are discussed in the last part of this review, particularly in the understanding
      of carotenoid metabolism pathways and the genetics of carotenoid coloration. We
      suggest that carotenoid metabolism and transport are important proximate
      mechanisms responsible for individual and population-differences in cichlid
      coloration that may ultimately contribute to diversification and speciation.

PMID- 24667559
TI  - Lipoprotein metabolism indicators improve cardiovascular risk prediction.
AB  - BACKGROUND: Cardiovascular disease risk increases when lipoprotein metabolism is
      dysfunctional. We have developed a computational model able to derive indicators
      of lipoprotein production, lipolysis, and uptake processes from a single
      lipoprotein profile measurement. This is the first study to investigate whether
      lipoprotein metabolism indicators can improve cardiovascular risk prediction and
      therapy management. METHODS AND RESULTS: We calculated lipoprotein metabolism
      indicators for 1981 subjects (145 cases, 1836 controls) from the Framingham Heart
      Study offspring cohort in which NMR lipoprotein profiles were measured. We
      applied a statistical learning algorithm using a support vector machine to select
      conventional risk factors and lipoprotein metabolism indicators that contributed
      to predicting risk for general cardiovascular disease. Risk prediction was
      quantified by the change in the Area-Under-the-ROC-Curve (DeltaAUC) and by risk
      reclassification (Net Reclassification Improvement (NRI) and Integrated
      Discrimination Improvement (IDI)). Two VLDL lipoprotein metabolism indicators
      (VLDLE and VLDLH) improved cardiovascular risk prediction. We added these
      indicators to a multivariate model with the best performing conventional risk
      markers. Our method significantly improved both CVD prediction and risk
      reclassification. CONCLUSIONS: Two calculated VLDL metabolism indicators
      significantly improved cardiovascular risk prediction. These indicators may help
      to reduce prescription of unnecessary cholesterol-lowering medication, reducing
      costs and possible side-effects. For clinical application, further validation is
      required.

PMID- 24667560
TI  - TRAIL deficiency contributes to diabetic nephropathy in fat-fed ApoE-/- mice.
AB  - BACKGROUND: We recently demonstrated that TNF-related apoptosis-inducing ligand
      (TRAIL) is protective of diet-induced diabetes in mice. While TRAIL has been
      implicated in chronic kidney disease, its role in vivo in diabetic nephropathy is
      not clear. The present study investigated the role of TRAIL in the pathogenesis
      of diabetic nephropathy using TRAIL(-/-)ApoE(-/-) mice. METHODS: TRAIL(-/-)ApoE(
      /-) and ApoE(-/-) mice were fed a high fat diet for 20 w. Plasma glucose and
      insulin levels were assessed over 0, 5, 8 and 20 w. At 20 w, markers of kidney
      function including creatinine, phosphate, calcium and cystatin C were measured.
      Changes in mRNA expression of MMPs, TIMP-1, IL-1beta and IL-18 were assessed in
      the kidney. Functional and histological changes in kidneys were examined. Glucose
      and insulin tolerance tests were performed. RESULTS: TRAIL(-/-)ApoE(-/-) mice had
      significantly increased urine protein, urine protein:creatinine ratio, plasma
      phosphorous, and plasma cystatin C, with accelerated nephropathy. Histologically,
      increased extracellular matrix, mesangial expansion and mesangial cell
      proliferation in the glomeruli were observed. Moreover, TRAIL(-/-)ApoE(-/-)
      kidneys displayed loss of the brush border and disorganisation of tubular
      epithelium, with increased fibrosis. TRAIL-deficient kidneys also had increased
      expression of MMPs, TIMP-1, PAI-1, IL-1beta and IL-18, markers of renal injury
      and inflammation. Compared with ApoE(-/-) mice, TRAIL-/-ApoE-/- mice displayed
      insulin resistance and type-2 diabetic features with reduced renal insulin
      receptor expression. CONCLUSIONS: Here, we show that TRAIL-deficiency in ApoE(-/
      ) mice exacerbates nephropathy and insulin resistance. Understanding TRAIL
      signalling in kidney disease and diabetes, may therefore lead to novel strategies
      for the treatment of diabetic nephropathy.

PMID- 24667562
TI  - The evolutionary biology of musical rhythm: was Darwin wrong?
AB  - In The Descent of Man, Darwin speculated that our capacity for musical rhythm
      reflects basic aspects of brain function broadly shared among animals. Although
      this remains an appealing idea, it is being challenged by modern cross-species
      research. This research hints that our capacity to synchronize to a beat, i.e.,
      to move in time with a perceived pulse in a manner that is predictive and
      flexible across a broad range of tempi, may be shared by only a few other
      species. Is this really the case? If so, it would have important implications for
      our understanding of the evolution of human musicality. 

PMID- 24667561
TI  - Routes of allergic sensitization and myeloid cell IKKbeta differentially regulate
      antibody responses and allergic airway inflammation in male and female mice.
AB  - Gender influences the incidence and/or the severity of several diseases and
      evidence suggests a higher rate of allergy and asthma among women. Most
      experimental models of allergy use mice sensitized via the parenteral route
      despite the fact that the mucosal tissues of the gastrointestinal and respiratory
      tracts are major sites of allergic sensitization and/or allergic responses. We
      analyzed allergen-specific Ab responses in mice sensitized either by gavage or
      intraperitoneal injection of ovalbumin together with cholera toxin as adjuvant,
      as well as allergic inflammation and lung functions following subsequent nasal
      challenge with the allergen. Female mice sensitized intraperitoneally exhibited
      higher levels of serum IgE than their male counterparts. After nasal allergen
      challenge, these female mice expressed higher Th2 responses and associated
      inflammation in the lung than males. On the other hand, male and female mice
      sensitized orally developed the same levels of allergen-specific Ab responses and
      similar levels of lung inflammation after allergen challenge. Interestingly, the
      difference in allergen-specific Ab responses between male and female mice
      sensitized by the intraperitoneal route was abolished in IKKbetaDeltaMye mice,
      which lack IKKbeta in myeloid cells. In summary, the oral or systemic route of
      allergic sensitization and IKKbeta signaling in myeloid cells regulate how the
      gender influences allergen-specific responses and lung allergic inflammation. 

PMID- 24667564
TI  - Science, policy, and the transparency of values.
AB  - BACKGROUND: Opposing groups of scientists have recently engaged in a heated
      dispute over a preliminary European Commission (EC) report on its regulatory
      policy for endocrine-disrupting chemicals. In addition to the scientific issues
      at stake, a central question has been how scientists can maintain their
      objectivity when informing policy makers. OBJECTIVES: Drawing from current
      ethical, conceptual, and empirical studies of objectivity and conflicts of
      interest in scientific research, we propose guiding principles for communicating
      scientific findings in a manner that promotes objectivity, public trust, and
      policy relevance. DISCUSSION: Both conceptual and empirical studies of scientific
      reasoning have shown that it is unrealistic to prevent policy-relevant scientific
      research from being influenced by value judgments. Conceptually, the current
      dispute over the EC report illustrates how scientists are forced to make value
      judgments about appropriate standards of evidence when informing public policy.
      Empirical studies provide further evidence that scientists are unavoidably
      influenced by a variety of potentially subconscious financial, social, political,
      and personal interests and values. CONCLUSIONS: When scientific evidence is
      inconclusive and major regulatory decisions are at stake, it is unrealistic to
      think that values can be excluded from scientific reasoning. Thus, efforts to
      suppress or hide interests or values may actually damage scientific objectivity
      and public trust, whereas a willingness to bring implicit interests and values
      into the open may be the best path to promoting good science and policy.

PMID- 24667563
TI  - Reference gene selection for quantitative real-time RT-PCR normalization in the
      half-smooth tongue sole (Cynoglossus semilaevis) at different developmental
      stages, in various tissue types and on exposure to chemicals.
AB  - Quantitative real time RT-PCR has been described as the most sensitive method for
      the detection of low abundance mRNA. To date, no reference genes have been
      screened in the half-smooth tongue sole (Cynoglossus semilaevis). The aim of this
      study was to select the most stable genes for quantitative real-time RT-PCR.
      Eight housekeeping genes (18S, TUBA, B2M, ACTB, EF1A, GAPDH, RPL17 and UBCE) were
      tested at different developmental stages, in different tissues, and following
      exposure to the drug SB-431542. Using geNorm, BestKeeper and NormFinder software,
      GAPDH/B2M, GAPDH/18S and UBCE/GAPDH were identified as the most suitable genes
      from samples taken of different developmental stages while 18S/RPL17 were
      consistently ranked as the best reference genes for different tissue types.
      Furthermore, TUBA/B2M, TUBA/UBCE and B2M/TUBA were found to be the most suitable
      genes in samples treated with the drug, SB-431542 by geNorm, BestKeeper and
      NormFinder respectively. Across both different developmental stages and tissue
      types, the combination of 18S and GAPDH was the most stable reference gene
      analyzed by Ref-Finder. To test and verify the screened reference genes, the
      expression profiles of LEFTY-normalized to the combination of GAPDH/18S and ACTB
      were presented. These results will be useful for future gene-expression studies
      in the half-smooth tongue sole. 

PMID- 24667565
TI  - In vitro metabolism of the alkaloid piplartine by rat liver microsomes.
AB  - Because piplartine (PPT) has demonstrated biological activities, such as
      cytotoxic, anxiolytic, antidepressant, antifungal and antiplatelet activities,
      this molecule is a relevant drug candidate. The metabolic fate of drug candidates
      is an essential requirement in assessing their safety and efficacy. Based on this
      requirement, the biotransformation of PPT by cytochrome P450 enzymes (CYP) was
      investigated for the first time. To determine the in vitro enzymatic kinetic
      parameters, an HPLC method was developed and validated to quantify PPT. All
      samples were separated on a reversed-phase C18 column using a mobile phase of
      acetonitrile:water (40:60, v/v). The method exhibited a linear range of 2.4-157.7
      MUmol/L, with the following calibration curve: y=0.0934 (+/-0.0010)x+0.0027,
      r=0.9975. The lower limit of quantitation was verified to be 2.4 MUmol/L, with an
      RSD below 7%. The precision and accuracy were assessed for both within-day and
      between-day determinations; neither relative standard (RSD%) deviations nor
      relative errors (RER) exceeded a value of 15%. The mean absolute recovery was
      85%, with an RSD value below 6%. The enzymatic kinetic parameters revealed a
      sigmoidal profile, with V(max)=4.7+/-0.3 MUmol/mg mL-1/min, h=2.5+/-0.4,
      S50=44.7+/-0.3 MUmol/L and CL(max)=0.054 MUL/min/mg protein, indicating
      cooperativity behavior. Employing a mammalian model, PPT metabolism yielded two
      unreported monohydroxylated products (m/z 334). The identification and structural
      elucidation of the metabolites were performed by comparing their mass spectra
      with those spectra of the parent drug. For the first time, the in vitro
      metabolism studies employing microsomes were demonstrated to be a suitable tool
      for data regarding enzymatic kinetics and for the metabolites formed in the PPT
      mammalian metabolism.

PMID- 24667566
TI  - Flow injection combined with ICP-MS for accurate high throughput analysis of
      elemental impurities in pharmaceutical products according to USP <232>/<233>.
AB  - New guidelines of the United States Pharmacopeia (USP), European Pharmacopeia
      (EP) and international organization (ICH, International Conference on
      Harmonization) regulating elemental impurity limits in pharmaceuticals seal the
      end of unspecific analysis of metal(oid)s as outlined in USP <231> and EP 2.4.8.
      Chapter USP <232> and EP 5.20 as well as drafts from ICH Q3D specify both daily
      doses and concentration limits of metallic impurities in pharmaceutical final
      products and in active pharmaceutical ingredients (API) and excipients. In
      chapters USP <233> and EP 2.4.20 method implementation, validation and quality
      control during the analytical process are described. By contrast with the--by now
      -applied methods, substance specific quantitative analysis features new basic
      requirements, further, significantly lower detection limits ask for the necessity
      of a general changeover of the methodology toward sensitive multi element
      analysis by ICP-AES and ICP-MS, respectively. A novel methodological approach
      based on flow injection analysis and ICP-SFMS/ICP-QMS for the quick and accurate
      analysis of Cd, Pb, As, Hg, Ir, Os, Pd, Pt, Rh, Ru, Cr, Mo, Ni, V, Cu, Mn, Fe and
      Zn in drug products by prior dilution, dissolution or microwave assisted closed
      vessel digestion according to the regulations is presented. In comparison to the
      acquisition of continuous signals, this method is advantageous with respect to
      the unprecedented high sample throughput due to a total analysis time of
      approximately 30s and the low sample consumption of below 50 MUL, while meeting
      the strict USP demands on detection/quantification limits, precision and
      accuracy.

PMID- 24667567
TI  - Testing of potential glycan-based heparanase inhibitors in a fluorescence
      activity assay using either bacterial heparinase II or human heparanase.
AB  - Heparanase, an endo-beta-glucuronidase cleaving heparan sulfate (HS) chains at
      cell surfaces and in the extracellular matrix (ECM), is involved in angiogenesis,
      tumor progression and metastasis as well as in inflammation and kidney
      dysfunction. Therefore, heparanase is considered a promising therapeutic target
      and diagnostic marker. Recently, we have developed a simple, rapid, fully
      automatable fluorimetric activity assay using the synthetic sulfated
      pentasaccharide fondaparinux as substrate and bacterial heparinase II (HEP-II)
      instead of human heparanase (hHEP). The aim of this study was to evaluate this
      assay for inhibitor testing as well as to check whether the assay principle is
      applicable to measure the activity and inhibition, respectively, of the actual
      target enzyme hHEP. Besides the known hHEP inhibitor suramin and the
      antiinflammatory and antimetastatic PS3, two series of beta-1,3-glucan sulfates
      differing in their chain length and degree of sulfation, further semisynthetic
      sulfated glycans, and two sulfated polysaccharides isolated from algae were
      included to examine structure-activity relationships. The inhibitory activity of
      sulfated glycans showed to be greatly dependent on both their degree of sulfation
      and their basic glycan structure, but independent of their molecular size. The
      beta-1,3-glucan sulfates were superior to suramin as well as to the other glycans
      with similar degree of sulfations. The most active inhibitor was found to be the
      beta-1,3-glucan sulfate PS3 (IC50=0.017 MUM). By using hHEP instead of HEP-II
      comparable results were obtained. With an IC50 being about 160 times lower than
      that of suramin, PS3 exhibited again the strongest inhibitory effects. Inhibition
      of hHEP may therefore contribute to the potent antiinflammatory and
      antimetastatic activities of PS3 in vivo. In conclusion, the fluorimetric hHEP
      activity assay proved to be a simple, fully automatable tool for testing
      potential inhibitors. In case of HS mimetic inhibitors, the assay variant with
      HEP-II may provide a fast and inexpensive option for initial screening purposes.

PMID- 24667569
TI  - En face spectral domain optical coherence tomography analysis of lamellar macular
      holes.
AB  - PURPOSE: To analyze the anatomical characteristics of lamellar macular holes
      using cross-sectional and en face spectral domain optical coherence tomography.
      METHODS: Forty-two lamellar macular holes were retrospectively identified for
      analysis. The location, cross-sectional length, and area of lamellar holes were
      measured using B-scans and en face imaging. The presence of photoreceptor inner
      segment/outer segment disruption and the presence or absence of epiretinal
      membrane formation were recorded. RESULTS: Forty-two lamellar macular holes were
      identified. Intraretinal splitting occurred within the outer plexiform layer in
      97.6% of eyes. The area of intraretinal splitting in lamellar holes did not
      correlate with visual acuity. Eyes with inner segment/outer segment disruption
      had significantly worse mean logMAR visual acuity (0.363 +/- 0.169; Snellen =
      20/46) than in eyes without inner segment/outer segment disruption (0.203 +/-
      0.124; Snellen = 20/32) (analysis of variance, P = 0.004). Epiretinal membrane
      was present in 34 of 42 eyes (81.0%). CONCLUSION: En face imaging allowed for
      consistent detection and quantification of intraretinal splitting within the
      outer plexiform layer in patients with lamellar macular holes, supporting the
      notion that an area of anatomical weakness exists within Henle's fiber layer,
      presumably at the synaptic connection of these fibers within the outer plexiform
      layer. However, the en face area of intraretinal splitting did not correlate with
      visual acuity, disruption of the inner segment/outer segment junction was
      associated with significantly worse visual acuity in patients with lamellar
      macular holes.

PMID- 24667568
TI  - Improving furosemide polymorphs properties through supramolecular complexes of
      beta-cyclodextrin.
AB  - In this work, complexes of beta-cyclodextrin and the two solid forms of
      furosemide were prepared and characterized for their potential pharmaceutical
      applications, with the interactions between the two compounds being studied in
      the solution and solid states. The solubility studies revealed different
      behaviors of the polymorphs. In particular, it was observed that the binary
      complex significantly increased the solubility of furosemide form I in the
      gastric simulated fluid, which resulted in a rise in the bioavailability of this
      formulation after oral administration. In addition, results using ssNMR, FT-IR,
      DSC, TGA, SEM and XRPD provided evidence of the formation of complexes after
      utilizing kneading and freeze-drying methods. A comparison with previous
      developed complexes that used maltodextrin as the ligand was performed. Our
      results suggest that these novel supramolecular complexes showed promise to be
      used in drug delivery systems with an application in pharmaceutical formulations.

PMID- 24667570
TI  - Subfoveal choroidal thickness change after intravitreal ranibizumab for
      idiopathic choroidal neovascularization.
AB  - PURPOSE: To investigate changes in subfoveal choroidal thickness (SFCT) after
      intravitreal injections of ranibizumab for idiopathic subfoveal choroidal
      neovascularization (ISCNV). METHODS: The prospective consecutive case series
      study included 16 patients with unilateral ISCNV. All eyes with ISCNV were
      treated with a single intravitreal injection of 0.5 mg ranibizumab followed by as
      needed dosing. Subfoveal choroidal thickness was measured using enhanced depth
      imaging optical coherence tomography. RESULTS: The mean total follow-up time was
      4.9 +/- 1.5 months, and the follow-up after the last intravitreal ranibizumab
      injection was 4.4 +/- 1.3 months. In the treated eyes, the SFCT decreased
      significantly from 354 +/- 84 MUm at baseline to 328 +/- 79 MUm at 1 month later
      (P < 0.001) and reincreased (P = 0.02) to 342 +/- 75 MUm at the final visit (P =
      0.15 versus baseline value). Change in SFCT was marginally (P = 0.11) associated
      with the change in retinal foveal thickness. In the contralateral unaffected
      eyes, the SFCT did not change significantly during follow-up (P = 0.76).
      CONCLUSION: In patients with unilateral ISCNV, intravitreal ranibizumab therapy
      was associated with a thinning of an abnormally thick subfoveal choroid,
      marginally in association with a parallel decrease in retinal foveal thickness.
      It remained elusive whether the choroidal thinning was due to a direct
      pharmacological effect of ranibizumab or whether it was secondary due to the
      foveal retinal thinning. In view of the significant differences in SFCT between
      affected eyes and unaffected contralateral eyes at baseline and in view of the
      significant therapy-associated decrease in SFCT, the potential role of SFCT as an
      additional marker for the diagnosis and follow-up of ISCNV and other neovascular
      maculopathies may be examined in future studies.

PMID- 24667572
TI  - Engineered nanocrystal technology: in-vivo fate, targeting and applications in
      drug delivery.
AB  - Formulation of nanocrystals is a robust approach which can improve delivery of
      poorly water soluble drugs, a challenge pharmaceutical industry has been facing
      since long. Large scale production of nanocrystals is done by techniques like
      precipitation, media milling and, high pressure homogenization. Application of
      appropriate stabilizers along with drying accords long term stability and
      commercial viability to nanocrystals. These can be administered through oral,
      parenteral, pulmonary, dermal and ocular routes showing their high therapeutic
      applicability. They serve to target drug molecules in specific regions through
      size manipulation and surface modification. This review dwells upon the in-vivo
      fate and varying applications in addition to the facets of drug nanocrystals
      stated above. 

PMID- 24667571
TI  - Utility of intraoperative optical coherence tomography during vitrectomy surgery
      for vitreomacular traction syndrome.
AB  - PURPOSE: To assess the microarchitectural changes occurring during surgery for
      vitreomacular traction using intraoperative optical coherence tomography (iOCT).
      METHODS: A retrospective, consecutive case series of eyes undergoing pars plana
      vitrectomy for vitreomacular traction with performance of concurrent iOCT. A
      custom, microscope-mounted portable spectral domain optical coherence tomography
      system was used. Clinical characteristics and iOCT images were analyzed. RESULTS:
      Twelve eyes of 12 patients were included with a mean preoperative visual acuity
      of 20/78 improving to 20/51 (P = 0.02), postoperatively. Intraoperative optical
      coherence tomography was successfully performed in 100% of cases.
      Microarchitectural changes were noted on iOCT after surgical release of the
      vitreomacular traction particularly in the outer retina with increased subretinal
      hyporeflectivity (e.g., expansion of the distance between the retinal pigment
      epithelium and photoreceptor layers). In 5 of 12 eyes (42%), iOCT findings
      altered the surgical procedure (e.g., internal limiting membrane peeling, gas
      tamponade) to address the subclinical findings (e.g., full-thickness macular hole
      formation, residual membrane). CONCLUSION: Intrasurgical imaging using iOCT
      during vitreomacular traction surgery may identify subclinical changes (e.g.,
      occult full-thickness macular hole formation) that may impact surgical decision
      making. Architectural changes may occur after surgical maneuvers that are
      particularly noted in the outer retina. The functional significance of these
      changes requires further investigation.

PMID- 24667573
TI  - Cancer specific mortality in insulin-treated type 2 diabetes patients.
AB  - AIMS: To test the hypothesis that cumulative exposure to insulin and long-acting
      insulin analogs might be associated with cancer mortality in diabetes patients.
      METHODS: All consecutive diabetes patients aged over 40 years, residing in a
      major urban area were screened at their first diabetes outpatient visit between
      01/01/2001-12/31/2008 (n = 79869). Exclusion criteria were insulin treatment at
      screening, no insulin treatment until 12/31/2008, less than 6 months of glucose
      lowering treatment alone before insulin initiation, insulin prescription before
      glargine became available, age <40/>= 80 years at first insulin prescription, and
      <6 months of insulin exposure. A total 4990 subjects were followed-up for death
      based on death certificate, until 12/31/2011. Adjusted time-dependent competing
      risk regression analysis, with daily updates of treatment modalities was
      performed. Results are expressed for every 10,000 IU of cumulative dose or one
      year of cumulative time exposure to insulin. RESULTS: Mean baseline age was 62 +/
      9 years, and follow-up 4.7 +/- 1.9 years. Glargine cumulative dose was
      associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI
      0.89-0.99, p = 0.033)). Cumulative exposure limited to that attained one year
      prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89-0.99, p
      = 0.018)) and cumulative dose of glargine (0.92 (95%CI 0.86-0.98, p = 0.014)).
      Glargine cumulative time and cumulative dose were significant predictors for
      lower pancreatic and breast cancer mortality, but not for deaths from lung,
      colorectal, female genital, liver, and urinary tract cancer. No increased hazards
      were found for any other subtypes of insulins. CONCLUSIONS: The cumulative dose
      exposure to insulin glargine was associated with a lower risk of cancer mortality
      in general, and of breast and pancreatic cancer in particular. This effect
      remained even after additional "fixed" cohort or propensity score analyses.

PMID- 24667574
TI  - Reversed theta sequences of hippocampal cell assemblies during backward travel.
AB  - Hippocampal cell assemblies coding for past, present and future events form theta
      timescale (~100 ms) sequences that represent spatio-temporal episodes. However,
      the underlying mechanisms remain largely unknown. We recorded hippocampal and
      entorhinal cortical activity as rats experienced backward travel on a model
      train. Although the firing fields of place cells remained stable, the order in
      which they were activated in the theta sequence was reversed during backward
      travel. Thus, hippocampal cell assemblies coordinated their relative timing to
      correctly predict the sequential traversal of place fields in reverse order. At
      the single-cell level, theta phase represented distance traveled through the
      field, even though the head of the rat was oriented opposite to travel direction
      and entorhinal head-direction cells maintained their preferred firing direction.
      Our results challenge most theoretical models of theta sequence generation in the
      hippocampus.

PMID- 24667575
TI  - Esophageal eosinophilia is increased in rural areas with low population density:
      results from a national pathology database.
AB  - OBJECTIVES: Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic
      disease arising from an allergy/immune-mediated process. Generally, the risk of
      atopic disease differs in rural and urban environments. The relationship between
      population density and EoE is unknown. Our aim was to assess the relationship
      between EoE and population density. METHODS: We conducted a cross-sectional, case
      control study of patients with esophageal biopsies in a US national pathology
      database between January 2009 and June 2012 to assess the relationship between
      population density and EoE. Using geographic information systems, the population
      density (individuals per square mile) was determined for each patient zip code.
      The odds of esophageal eosinophilia and EoE were estimated for each quintile of
      population density and adjusted for potential confounders. Sensitivity analyses
      were conducted with varying case definitions and to evaluate the potential for
      bias from endoscopy volume and patient factors. RESULTS: Of 292,621 unique
      patients in the source population, 89,754 had normal esophageal biopsies and
      14,381 had esophageal eosinophilia with >=15 eosinophils per high-power field.
      The odds of having esophageal eosinophilia increased with decreasing population
      density (P for trend <0.001). Compared with those in the highest quintile of
      population density, odds of having esophageal eosinophilia were significantly
      higher among those in the lowest quintile of population density (adjusted odds
      ratio (aOR) 1.27, 95% confidence interval (CI): 1.18, 1.36). A similar dose
      response trend was observed across case definitions with increased odds of EoE in
      the lowest population density quintile (aOR 1.59, 95% CI: 1.45-1.76). Estimates
      were robust to sensitivity analyses. CONCLUSIONS: Population density is strongly
      and inversely associated with esophageal eosinophilia and EoE. This association
      is robust to varying case definitions and adjustment factors. Environmental
      exposures that are more prominent in rural areas may be relevant to the
      pathogenesis of EoE.

PMID- 24667576
TI  - Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK
      over two decades: population-based study.
AB  - OBJECTIVES: Few studies have quantified the incidence and prevalence of celiac
      disease (CD) and dermatitis herpetiformis (DH) nationally and regionally by time
      and age groups. Understanding this epidemiology is crucial for hypothesizing
      about causes and quantifying the burden of disease. METHODS: Patients with CD or
      DH were identified in the Clinical Practice Research Datalink between 1990 and
      2011. Incidence rates and prevalence were calculated by age, sex, year, and
      region of residence. Incidence rate ratios (IRR) adjusted for age, sex, and
      region were calculated with Poisson regression. RESULTS: A total of 9,087
      incident cases of CD and 809 incident cases of DH were identified. Between 1990
      and 2011, the incidence rate of CD increased from 5.2 per 100,000 (95% confidence
      interval (CI), 3.8-6.8) to 19.1 per 100,000 person-years (95% CI, 17.8-20.5; IRR,
      3.6; 95% CI, 2.7-4.8). The incidence of DH decreased over the same time period
      from 1.8 per 100,000 to 0.8 per 100,000 person-years (average annual IRR, 0.96;
      95% CI, 0.94-0.97). The absolute incidence of CD per 100,000 person-years ranged
      from 22.3 in Northern Ireland to 10 in London. There were large regional
      variations in prevalence for CD but not DH. CONCLUSIONS: We found a fourfold
      increase in the incidence of CD in the United Kingdom over 22 years, with large
      regional variations in prevalence. This contrasted with a 4% annual decrease in
      the incidence of DH, with minimal regional variations in prevalence. These
      contrasts could reflect differences in diagnosis between CD (serological
      diagnosis and case finding) and DH (symptomatic presentation) or the possibility
      that diagnosing and treating CD prevents the development of DH.

PMID- 24667577
TI  - Adiponectin enhances intercellular adhesion molecule-1 expression and promotes
      monocyte adhesion in human synovial fibroblasts.
AB  - Adiponectin is a protein hormone secreted predominantly by differentiated
      adipocytes and is involved in energy homeostasis. Adiponectin expression is
      significantly high in the synovial fluid of patients with osteoarthritis (OA).
      Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that
      mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin
      induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was
      examined by using qPCR, flow cytometry and western blotting. The intracellular
      signaling pathways were investigated by pretreated with inhibitors or
      transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion
      assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1
      expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors
      (AraA and compound C) or transfection with siRNA against AMPKalpha1 and two AMPK
      upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein
      kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression.
      Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII,
      AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter.
      In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1
      pathway increased the adhesion of monocytes to the OASF monolayer. Our results
      suggest that adiponectin increases ICAM-1 expression in human OASFs via the
      LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1
      expression promoted the adhesion of monocytes to human OASFs. These findings may
      provide a better understanding of the pathogenesis of OA and can utilize this
      knowledge to design a new therapeutic strategy. 

PMID- 24667578
TI  - Implied dynamics biases the visual perception of velocity.
AB  - We expand the anecdotic report by Johansson that back-and-forth linear harmonic
      motions appear uniform. Six experiments explore the role of shape and spatial
      orientation of the trajectory of a point-light target in the perceptual judgment
      of uniform motion. In Experiment 1, the target oscillated back-and-forth along a
      circular arc around an invisible pivot. The imaginary segment from the pivot to
      the midpoint of the trajectory could be oriented vertically downward (consistent
      with an upright pendulum), horizontally leftward, or vertically upward (upside
      down). In Experiments 2 to 5, the target moved uni-directionally. The effect of
      suppressing the alternation of movement directions was tested with curvilinear
      (Experiment 2 and 3) or rectilinear (Experiment 4 and 5) paths. Experiment 6
      replicated the upright condition of Experiment 1, but participants were asked to
      hold the gaze on a fixation point. When some features of the trajectory evoked
      the motion of either a simple pendulum or a mass-spring system, observers
      identified as uniform the kinematic profiles close to harmonic motion. The bias
      towards harmonic motion was most consistent in the upright orientation of
      Experiment 1 and 6. The bias disappeared when the stimuli were incompatible with
      both pendulum and mass-spring models (Experiments 3 to 5). The results are
      compatible with the hypothesis that the perception of dynamic stimuli is biased
      by the laws of motion obeyed by natural events, so that only natural motions
      appear uniform. 

PMID- 24667579
TI  - Peripheral CD4CD8 double positive T cells with a distinct helper cytokine profile
      are increased in rheumatoid arthritis.
AB  - Peripheral CD4CD8 double positive (DP) T cells have been reported to play a role
      in several autoimmune diseases, virus infections and cancer. In rheumatoid
      arthritis (RA), both CD4 and CD8 single positive (SP) T cells are known to be
      involved in the pathogenesis, but the role of peripheral CD4CD8 DP T cells has
      not been investigated in detail. Anti cyclic citrullinated antibodies (ACPA)
      positive and ACPA negative RA patients, patients with systemic lupus
      erythematodes (SLE) and age matched healthy donors (HD) were enrolled in the
      analysis. The frequencies and phenotype of DP T cells in PBMC were investigated.
      In addition, DP T cells were quantified in biopsies from rheumatoid synovium.
      After in vitro restimulation, the cytokine production of DP T cells was
      investigated in cultures of PBMC. CMV specific cytokine secretion as well as
      proliferation was analyzed following antigen specific restimulation after an
      appropriate culture duration. DP T cells were found more frequently in RA
      patients than in healthy controls or patients with SLE. These DP T cells express
      alphabeta TCRs, are of a memory phenotype and share features of both CD4 as well
      as CD8 SP T cells. Importantly, DP T cells were found to also be present in the
      rheumatoid synovium. Further characterization of DP T cells from RA patients
      revealed increased production of IL-21 and IL-4, implying a possible role as T
      helper cells. In addition, DP T cells in RA seem to contribute to the
      inflammatory process, because they produce significantly more IFNgamma than
      counterparts from HD and are increased in CMV+ RA patients. Given their capacity
      to produce a variety of cytokines (IL4, IL21 and IFNgamma), their association
      with ACPA positive RA and their presence in the synovium, we suggest an important
      role of double positive T cells in the pathogenesis of rheumatoid arthritis. 

PMID- 24667580
TI  - Insulin-like growth factor 1 receptor (IGF-1R) as a target of MiR-497 and plasma
      IGF-1R levels associated with TNM stage of pancreatic cancer.
AB  - The expression levels and regulatory roles of miR-497 in pancreatic cancer are
      unclear. The clinical value of plasma insulin-like growth factor 1 receptor (IGF
      1R) in pancreatic cancers has not been investigated. In the present study, we
      demonstrated that miR-497 was significantly downregulated in pancreatic cancer
      tissues. Upregulation of miR-497 in BxPC-3 and AsPC-1 pancreatic cancer cell
      lines inhibited proliferation, enhanced apoptosis, re-sensitized cells to
      gemcitabine and suppressed IGF-1R and p-AKT expression through direct
      downregulation of IGF-1R protein expression. Opposite effects were observed after
      downregulation of miR-497. Plasma IGF-1R levels in patients with pancreatic
      cancer increased significantly, compared with that in patients with chronic
      pancreatitis, other pancreatic tumors and pancreatic neuroendocrine tumors (P =
      0.006, P = 0.018 and P = 0.004, respectively), and displayed potential values for
      distinguishing pancreatic lesions. However, the levels in pancreatic cancer
      patients were comparable to that in healthy volunteers (P = 0.095). The tumor
      locations and TNM stage were associated with plasma IGF-1R levels (P = 0.013 and
      P = 0.01, respectively). There was no significant difference of overall survival
      between high and low IGF-1R expression groups. In conclusion, we demonstrated
      that miR-497 attenuated the malignancy of pancreatic cancer cells and promoted
      sensitivity of cells to gemcitabine by directly downregulation of IGF-1R
      expression. Plasma IGF-1R displayed a potential value for distinguishing
      pancreatic lesions and could be a new biomarker for guiding TNM stage of
      pancreatic cancer.

PMID- 24667582
TI  - What is the optimal revascularization technique for isolated disease of the left
      anterior descending artery: minimally invasive direct coronary artery bypass or
      percutaneous coronary intervention?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was, 'What is the optimal revascularization
      technique for isolated disease of the left anterior descending artery (LAD) in
      terms of patient survival, morbidity such as myocardial infarction (MI) and need
      for repeat target vessel revascularization: minimally invasive direct coronary
      artery bypass graft (MIDCAB) or percutaneous coronary intervention (PCI)?'
      Altogether 504 papers were found using the reported search, of which 13
      represented the best evidence to answer the clinical question. Outcome parameters
      that were used in the assessment include the incidence of major adverse
      cardiovascular or cerebral events (MACCEs), mortality and the rate of repeat
      target vessel revascularization. The authors, journal, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of the papers are tabulated. One meta-analysis showed no
      significant difference in terms of individual incidences of MI, stroke or
      mortality, but when considered as a composite MACCE outcome, this was found to be
      significantly lower in the MIDCAB group. Moreover, further meta-analytical data
      have revealed a 5-fold increase in the need for repeat revascularization with
      PCI, with some centres reporting rates of up to 34%. However, retrospective data
      have shown that average length of hospital stay was longer in the MIDCAB group
      (7.4 +/- 3.2 vs 3.4 +/- 3.5 days; P < 0.001). We conclude that there are obvious
      proven benefits with MIDCAB, namely in terms of a reduced need for repeat target
      vessel revascularization and incidence of MACCE, and one study has even shown
      that there is a long-term survival benefit in 'real-world' clinical practice.
      However, given that there is a lack of well-powered randomized controlled trial
      and long-term follow-up data to prove a mortality benefit in support of MIDCAB,
      patients requiring revascularization of isolated proximal LAD stenosis and being
      considered for percutaneous coronary intervention should be discussed in a
      multidisciplinary team setting prior to intervention. 

PMID- 24667581
TI  - Chemoprevention of esophageal cancer with black raspberries, their component
      anthocyanins, and a major anthocyanin metabolite, protocatechuic acid.
AB  - Diets containing either freeze-dried black raspberries (BRBs) or their
      polyphenolic anthocyanins (ACs) have been shown to inhibit the development of N
      nitrosomethylbenzylamine (NMBA)-induced esophageal cancer in rats. The present
      study was conducted to determine whether PCA, a major microbial metabolite of
      black raspberry (BRB) ACs, also prevents NMBA-induced esophageal cancer in rats.
      F344 rats were injected with NMBA three times a week for 5 weeks and then fed
      control or experimental diets containing 6.1% BRBs, an anthocyanin (AC)-enriched
      fraction derived from BRBs, or protocatechuic acid (PCA). Animals were
      exsanguinated at weeks 15, 25, and 35 to quantify the development of
      preneoplastic lesions and tumors in the esophagus, and to relate this to the
      expression of inflammatory biomarkers. At weeks 15 and 25, all experimental diets
      were equally effective in reducing NMBA-induced esophageal tumorigenesis, as well
      as in reducing the expression of pentraxin-3 (PTX3), a cytokine produced by
      peripheral blood mononuclear cells in response to interleukin (IL)-1beta and TNF
      alpha. All experimental diets were also active at reducing tumorigenesis at week
      35; however, the BRB diet was significantly more effective than the AC and PCA
      diets. Furthermore, all experimental diets inhibited inflammation in the
      esophagus via reducing biomarker (COX-2, iNOS, p-NF-kappaB, and sEH) and cytokine
      (PTX3) expression. Overall, our data suggest that BRBs, their component ACs, and
      PCA inhibit NMBA-induced esophageal tumorigenesis, at least in part, by their
      inhibitory effects on genes associated with inflammation.

PMID- 24667583
TI  - The cost impact of short-term ventricular assist devices and extracorporeal life
      support systems therapies on the National Health Service in the UK.
AB  - OBJECTIVES: The objective of the study was to assess the cost of using different
      blood pumps for short-term ventricular assist device (VAD) and extracorporeal
      life support (ECLS) systems for cardiac and cardiorespiratory failure in the UK.
      METHODS: The cost analysis presented was based on evaluation of the time required
      to provide circulatory support for the following indications: post-cardiac
      surgery cardiogenic shock, postacute myocardial infarction cardiogenic shock,
      deteriorating end-stage heart failure (ESHF) and the ability of different blood
      pumps to provide support for the necessary duration. The maximum length of
      support for each device was based on the manufacturers' recommendations. Direct
      medical cost of each treatment was evaluated only for the period of mechanical
      circulatory support in adults and children. Only the cost of device, placement
      and replacement procedures were considered. List prices were used for devices;
      resource use was based on expert opinion; unit costs were obtained from official
      UK sources and Wythenshawe hospital, Manchester, UK. Hospital perspective was
      utilized for analysis. Three VADs were selected for comparison in adults and two
      in children. Four centrifugal ECLS systems were selected for comparison in adults
      and two in children. RESULTS: In both VAD and ECLS indications, the CentriMag(r)
      was the least expensive when used for support of patients with end-stage heart
      failure. Compared with Cardiohelp(r) for ECLS (which has the same maximum claim
      duration of support of 30 days), CentriMag(r) lead to cost savings of L4294 per
      patient in all three clinical conditions considered. In post-cardiac surgery
      cardiogenic shock, CentriMag(r) VAD lead to savings of L5014 per patient compared
      with BPX-80. Results were robust in one-way sensitivity analysis in comparison
      with Cardiohelp(r). CONCLUSIONS: CentriMag(r) and PediVAS(r) blood pumps can lead
      to significant cost savings to the National Health Service, when used instead of
      other pumps for short-term VAD or ECLS treatment.

PMID- 24667584
TI  - Early prosthetic valve degeneration with Mitroflow aortic valves: determination
      of incidence and risk factors?.
AB  - OBJECTIVES: We describe a cluster of early valve degeneration (EVD) in a series
      of 281 Mitroflow valves implanted during 1999-2013. Patients with EVD were
      identified as having symptomatic stenosis or regurgitation within 6 years of
      implantation leading to reoperation. METHODS: Freedom from reoperation was
      estimated by Kaplan-Meier actuarial analysis. Patient and valve characteristics
      in the EVD group were compared with those without using univariate and Cox
      proportional hazard multivariate regression analysis. RESULTS: The rate of
      actuarial freedom from reoperation was 97% at 6 years and 92.5% at 10 years. The
      linearized rate of reoperation was 0.7% per patient-year. Ten patients required
      repeat surgery for EVD. Reoperation occurred from 2 years of implantation in
      patients with a mean age of 60, compared with 70 in those without EVD. Causes of
      explantation were stenosis (8), regurgitation (1) and mixed disease (1). The age
      was the only significant predictor of early degeneration; P = 0.03, hazard ratio
      = 2.89. Other factors analysed were atrial fibrillation, hypertension, chronic
      obstructive pulmonary disease, stroke, diabetes, preoperative angina, poor left
      ventricular function, renal dysfunction and extracardiac arteriopathy. There were
      no significant postoperative complications or operative mortality in those
      patients undergoing repeat surgery. CONCLUSIONS: There is an unexplained
      incidence (3.6%) of EVD resulting in explantation in some patients at 2 years
      after surgery. Mitroflow valves may not be suited to a younger age population.

PMID- 24667585
TI  - Is early surgical management of chylothorax following oesophagectomy beneficial?
AB  - A best evidence topic in surgery was written according to a structured protocol.
      The question addressed was whether the initial surgical management of chylothorax
      after oesophagectomy results in a better outcome. Altogether 357 papers were
      found as a result of the reported search, of which 4 represented the best
      evidence to answer the clinical question. The authors, journal, date and country
      of publication, patient group studied, study type, relevant outcomes and results
      of these papers were tabulated. Three studies were retrospective and from single
      centres with small patient numbers, while one study was a prospective, randomized
      controlled trial, from which a subgroup analysis was included in our results. We
      conclude that although all studies to date have had very small patient numbers
      and some contradictory results, there is some evidence that early surgical
      intervention of chylothorax following oesophagectomy reduces hospital stay when
      compared with conservative treatment. 

PMID- 24667586
TI  - Review of the evidence supports role for routine prophylaxis against
      postoperative supraventricular arrhythmia in patients undergoing pulmonary
      resection.
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was 'Is there an indication for routine
      prophylaxis against postoperative supraventricular arrhythmia in patients
      undergoing pulmonary resection surgery?' Altogether almost 150 papers were found
      as a result of the reported search, of which 14 represented the best evidence to
      reach conclusions regarding the issues of interest for this review. The major
      outcome of interest that was investigated was the incidence of supraventricular
      arrhythmia (SVA), notably atrial fibrillation (AF). The authors, journal, date
      and country of publication, patient group studied, study type, relevant outcomes,
      results and study weakness of the papers were tabulated. Current guidance from
      the Society of Thoracic Surgeons (STS) supports the use of diltiazem and
      amiodarone in most patients undergoing major pulmonary resection. Robust data
      from a large randomized, controlled trial (RCT) showed a reduction from 25 to 15%
      in the incidence of clinically significant atrial arrhythmia with diltiazem;
      P<0.03. Moreover, numerous RCTs have shown that there is a clear benefit with the
      use of amiodarone in reducing the incidence of postoperative SVA. Of note, one
      prospective clinical trial randomized 242 patients into a treatment group with
      amiodarone (n = 122) and a placebo group (n = 120). The incidence of
      postoperative AF was reduced from 32 to 9% in the active arm; P < 0.001. The risk
      of acute lung injury with amiodarone has not been substantiated further in more
      recent clinical trials and has in fact been shown to be safe. The STS guidelines
      do, however, advise against the use of amiodarone in extensive lung resection
      such as pneumonectomy. We conclude that there is an indication for routine
      prophylaxis against postoperative supraventricular arrhythmia in patients
      undergoing pulmonary resection. However, further data are needed to ascertain the
      impact of said anti-arrhythmic medications on the length of postoperative
      hospital stay, intensive care unit stay and cost. Those patients deemed high-risk
      need to be promptly identified, so the anti-arrhythmic therapy can be tailored to
      the cohort thus optimizing on cost and safety. 

PMID- 24667587
TI  - Parasites in the fossil record: a Cretaceous fauna with isopod-infested decapod
      crustaceans, infestation patterns through time, and a new ichnotaxon.
AB  - Parasites are common in modern ecosystems and are also known from the fossil
      record. One of the best preserved and easily recognisable examples of parasitism
      in the fossil record concerns isopod-induced swellings in the branchial chamber
      of marine decapod crustaceans. However, very limited quantitative data on the
      variability of infestation percentages at the species, genus, and family levels
      are available. Here we provide this type of data for a mid-Cretaceous (upper
      Lower Cretaceous, upper Albian) reef setting at Koskobilo, northern Spain, on the
      basis of 874 specimens of anomurans and brachyurans. Thirty-seven specimens
      (4.2%), arranged in ten species, are infested. Anomurans are more heavily
      infested than brachyurans, variability can be high within genera, and a
      relationship may exist between the number of specimens and infestation percentage
      per taxon, possibly suggesting host-specificity. We have also investigated
      quantitative patterns of infestation through geological time based on 88 infested
      species (25 anomurans, 55 brachyurans, seven lobsters, and one shrimp), to show
      that the highest number of infested species can be found in the Late Jurassic,
      also when corrected for the unequal duration of epochs. The same Late Jurassic
      peak is observed for the percentage of infested decapod species per epoch. This
      acme is caused entirely by infested anomurans and brachyurans. Biases (taphonomic
      and otherwise) and causes of variability with regard to the Koskobilo assemblage
      and infestation patterns through time are discussed. Finally, a new ichnogenus
      and -species, Kanthyloma crusta, are erected to accommodate such swellings or
      embedment structures (bioclaustrations). 

PMID- 24667588
TI  - Prevention of neonatal hepatitis B virus transmission.
AB  - Hepatitis B virus (HBV) vertical transmission remains a worldwide issue but is
      fairly uncommon in the western world due to routine screening and vaccination.
      Universal screening of pregnant women during the second trimester facilitates
      interruption of mother-to-child transmission (MTCT) by identifying HBV-infected
      mothers for whom intervention may reduce MTCT risk. HBV DNA level is the single
      most important predictor of MTCT. Other risk factors include HBeAg, HBe Ab, anti
      HB core IgG, and HIV status. Current recommendations for infants born to HBsAg
      positive mothers include administration of HBIG within 12 hours of birth and
      first dose of HBV vaccine within 24 hours of birth. Antiviral therapy is
      recommended in the third trimester of pregnancy in a subset of patients based on
      HBeAg and HBV DNA status for prophylaxis of MTCT, although discontinuation of
      antivirals after delivery is associated with significant increased risk of
      flares. This article outlines the data for prevention of vertical transmission of
      HBV. 

PMID- 24667589
TI  - Mucosal healing with thalidomide in refractory Crohn's disease patients
      intolerant of anti-TNF-alpha drugs: report of 3 cases and literature review.
AB  - Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor
      necrosis factor-alpha (TNF-alpha) activity. Several case reports and some
      clinical trials have demonstrated its efficacy in the treatment of refractory
      Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3
      patients with moderate-to-severe CD who were not responsive to anti-TNF-alpha
      therapies, and review the relevant literature. The first case is of a 28-year-old
      female affected by Crohn's colitis complicated by a severe fistulizing perianal
      disease; she was treated with infliximab, adalimumab, and certolizumab pegol,
      which were stopped because of intolerance. The second case is of a 39-year-old
      female with fistulizing ileocolitis complicated by severe arthralgias and
      perianal disease with loss of response to infliximab and intolerance of
      certolizumab pegol. The third case is of a 39-year-old male with gastric and
      ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All
      the 3 cases achieved complete clinical remission and endoscopic healing of
      mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients
      who experienced loss of response or were unable to tolerate anti-TNF-alpha drugs,
      thalidomide was an effective and well-tolerated therapy for inducing and
      maintaining long-term remission. 

PMID- 24667590
TI  - Fecal microbiota transplantation inducing remission in Crohn's colitis and the
      associated changes in fecal microbial profile.
AB  - Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine
      of unclear etiology. Increasing evidence has pointed to intestinal dysbiosis as a
      potential factor in a genetically susceptible individual. Fecal microbiota
      transplantation (FMT) has been used to treat inflammatory bowel disease with
      variable degrees of success. Herein, we report a patient with Crohn's colitis,
      previously failing an immunosuppressant, who achieved clinical, endoscopic, and
      histologic remission after a single fecal microbiota transplantation infusion. We
      have further characterized the changes in the fecal microbiota associated with
      this observation. 

PMID- 24667591
TI  - Impact of provider type on hepatitis C outcomes with boceprevir-based and
      telaprevir-based regimens.
AB  - GOALS: To examine the effect of provider type on outcomes and safety in a large
      hepatitis C virus (HCV)-infected cohort treated in routine medical practice.
      BACKGROUND: Nonphysician providers (NPP) are uniquely positioned to expand health
      care infrastructure to meet HCV treatment demands. STUDY: Retrospective,
      observational cohort analysis of 820 HCV genotype 1-infected veterans initiated
      on peginterferon/ribavirin and boceprevir or telaprevir in routine medical
      practice at 94 VA facilities before January 1, 2012 and followed through July 30,
      2013. Provider type was determined from prescription records and included
      physicians (MD) or NPPs (ie, nurse practitioners, physician assistants, and
      pharmacists). Inverse probability-of-treatment weighting and unweighted logistic
      regression analysis was used for comparison of sustained virologic response
      (SVR), treatment discontinuation rates, and adverse hematologic events. RESULTS:
      There was no significant difference in SVR by provider type overall (NPPs 52% vs.
      MDs 49%, P=0.33) and within patient subgroups, or in treatment discontinuation
      rates. In multivariate analyses, provider type was not associated with any
      significant difference in the odds of achieving SVR (NPP vs. MD; odds ratio 1.17;
      95% confidence interval, 0.84-1.63; P=0.37 inverse probability of treatment
      weighting; odds ration 1.16, 95% confidence interval, 0.84-1.59, P=0.38
      unweighted). Hematologic adverse event rates were similar: anemia: 57% NPP, 62%
      MD; thrombocytopenia: 43% NPP, 40% MD; neutropenia: 40% NPP, 39% MD. CONCLUSIONS:
      Treatment prescribed by NPPs was as likely to result in SVR as treatment
      prescribed by MDs, even after accounting for patient differences. Engaging more
      NPPs as HCV treatment providers may allow wider access to HCV treatment.

PMID- 24667592
TI  - Effects of probiotic intake and gender on nontyphoid Salmonella infection.
AB  - GOALS: The goal of the study was to examine if intake of Lactobacillus plantarum
      can accelerate clearance of nontyphoid Salmonella and reduce infection-related
      symptoms. BACKGROUND: Nontyphoid Salmonella is a major cause of gastroenteritis
      worldwide. Few studies have explored the effect of probiotics in these
      infections. STUDY: Patients with Salmonella infection were randomized to daily
      intake of 5 * 10 colony forming units of freeze-dried Lactobacillus plantarum 299
      v or placebo. Symptoms were recorded daily. Feces were cultured weekly. Treatment
      continued until 4 consecutive stool cultures negative for Salmonella had been
      obtained. RESULTS: The treatment and placebo groups did not differ significantly
      with regard to time to clearance of Salmonella, or time to resolution of
      symptoms. Irrespective of treatment, women tended to clear Salmonella more
      rapidly than men (19 vs. 28 d, P=0.18), despite a longer diarrheal phase (5 vs. 3
      days after inclusion, P=0.001). After Salmonella clearance (postinfectious
      phase), women experienced loose stools, nausea, and flatulence more frequently
      than men. In women, L. plantarum treatment was associated with more abdominal
      pain, whereas in men L. plantarum treatment reduced the prevalence of hard
      stools, and increased the presence of diarrheal symptoms in the postinfectious
      phase. CONCLUSIONS: Gender, but not administration of the probiotic strain L.
      plantarum 299 v, may influence acute symptoms during Salmonella infection and
      possibly clearance of Salmonella. Symptoms in the postinfectious phase were
      modified by the probiotics in a gender-specific way, but our results give little
      support for positive effects of L. plantarum 299 v treatment in nontyphoid
      salmonellosis.

PMID- 24667593
TI  - Prevalence and correlates of suspected nonalcoholic fatty liver disease in
      Chinese American children.
AB  - GOALS: The aim of this study was to evaluate the prevalence and clinical
      correlates of nonalcoholic fatty liver disease (NAFLD) in children of Chinese
      immigrants. BACKGROUND: NAFLD is increasing in prevalence and is frequently
      identified in children. High rates of NAFLD were found in adult Chinese
      immigrants. However, there are limited data regarding NAFLD in Chinese American
      children. STUDY: Clinical and laboratory data were collected from 407 children,
      aged 6 to 18 years, who had routine office visits at a Chinatown medical
      practice. Children were classified as having suspected NAFLD if common causes of
      liver disease were excluded, alanine aminotransferase levels exceeded established
      thresholds (>22.1 IU/L for girls and >25.8 IU/L for boys), and elevated alanine
      aminotransferase levels were confirmed by repeat measurement. RESULTS: 6.1% of
      Chinese American children had suspected NAFLD, including 33% of obese children.
      Seventeen percent of children were overweight, 14% were obese, and 52% had 25
      hydroxy vitamin D levels <20 ng/mL. In univariable analysis, children with
      suspected NAFLD were more frequently male, had higher body mass index percentile
      and lipid levels, and lower vitamin D levels compared with children without
      evidence of NAFLD. In multivariable analysis, suspected NAFLD was associated with
      higher BMI percentile and lower vitamin D levels when adjusting for other
      factors. CONCLUSIONS: Chinese American children with obesity are at high risk for
      NAFLD. They should be screened accordingly, including testing for metabolic
      disorders and low vitamin D levels. Early identification of NAFLD in childhood
      will allow for intervention with lifestyle modification, providing a means to
      reduce the prevalence of NAFLD in children and adults.

PMID- 24667594
TI  - Thoracoscopic long myotomy in the prone position to treat rapid esophageal
      contractions with normal latency.
AB  - A 56-year-old woman with an 8-year history of dysphagia and chest pain received a
      diagnosis of diffuse esophageal spasm by esophageal high-resolution manometry
      (HRM). Approximately 2 years of medical therapy was ineffective, and the
      patient's symptoms were worsening. Therefore, surgery was considered to be the
      most optimal treatment for this patient. The right thoracoscopic approach was
      selected because a long myotomy from the distal to proximal level of the
      esophagus was needed based on the HRM findings. The operation was performed in
      the prone position with establishment of pneumothorax. The total length of the
      myotomy was 16 cm, and the operation was finished within 2 hours. After the
      operation, the symptoms were considerably improved and no contractions were
      detected by HRM. The HRM findings before the operation were classified as rapid
      contractions with normal latency based on the 2012 Chicago classification of
      esophageal motility. Treatment for patients with rapid esophageal contractions
      with normal latency has not been previously described; however, treatment for
      diffuse esophageal spasm was considered to be pertinent to this patient. In
      conclusion, right thoracoscopic esophageal long myotomy in the prone position
      with establishment of pneumothorax may be useful when a proximal-level
      esophagomyotomy is required based on preoperative mapping by HRM. 

PMID- 24667595
TI  - Cloning and characterization of a wheat homologue of apurinic/apyrimidinic
      endonuclease Ape1L.
AB  - BACKGROUND: Apurinic/apyrimidinic (AP) endonucleases are key DNA repair enzymes
      involved in the base excision repair (BER) pathway. In BER, an AP endonuclease
      cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases
      and/or oxidative damage. A Triticum aestivum cDNA encoding for a putative
      homologue of ExoIII family AP endonucleases which includes E. coli Xth, human
      APE1 and Arabidopsis thaliana AtApe1L has been isolated and its protein product
      purified and characterized. METHODOLOGY/PRINCIPAL FINDINGS: We report that the
      putative wheat AP endonuclease, referred here as TaApe1L, contains AP
      endonuclease, 3'-repair phosphodiesterase, 3'-phosphatase and 3' -> 5'
      exonuclease activities. Surprisingly, in contrast to bacterial and human AP
      endonucleases, addition of Mg(2+) and Ca(2+) (5-10 mM) to the reaction mixture
      inhibited TaApe1L whereas the presence of Mn(2+), Co(2+) and Fe(2+) cations (0.1
      1.0 mM) strongly stimulated all its DNA repair activities. Optimization of the
      reaction conditions revealed that the wheat enzyme requires low divalent cation
      concentration (0.1 mM), mildly acidic pH (6-7), low ionic strength (20 mM KCl)
      and has a temperature optimum at around 20  degrees C. The steady-state kinetic
      parameters of enzymatic reactions indicate that TaApe1L removes 3'-blocking sugar
      phosphate and 3'-phosphate groups with good efficiency (kcat/KM = 630 and 485
      MUM(-1) . min(-1), respectively) but possesses a very weak AP endonuclease
      activity as compared to the human homologue, APE1. CONCLUSIONS/SIGNIFICANCE:
      Taken together, these data establish the DNA substrate specificity of the wheat
      AP endonuclease and suggest its possible role in the repair of DNA damage
      generated by endogenous and environmental factors.

PMID- 24667596
TI  - Digitalis-induced cell signaling by the sodium pump: on the relation of Src to
      Na(+)/K(+)-ATPase.
AB  - In addition to performing its essential transport function, the sodium pump also
      activates multiple cell signaling pathways in response to digitalis drugs such as
      ouabain. Based mainly on cell-free studies with mixtures of purified Src kinase
      and Na(+)/K(+)-ATPase, a well-advocated hypothesis on how ouabain initiates the
      activation of signaling pathways is that there is a preexisting physiological
      complex of inactive Src bound to the alpha-subunit of Na(+)/K(+)-ATPase, and that
      ouabain binding to this subunit disrupts the bound Src and activates it. Because
      of the published disagreements of the results of such cell-free experiments of
      two other laboratories, our aim was to attempt the resolution of these
      discrepancies. We reexamined the effects of ouabain, vanadate, and oligomycin on
      mixtures of Src, Na(+)/K(+)-ATPase, Mg(2+), and ATP as specified in prior
      studies; and assayed for Src-418 autophosphorylation as the measure of Src
      activation. In contrast to the findings of the proponents of the above
      hypothesis, our results showed similar effects of the three inhibitors of
      Na(+)/K(+)-ATPase; indicating that Src activation in such experiments is
      primarily due to the ATP-sparing effect of the ATPase inhibitor on the mixture of
      two enzymes competing for ATP. We conclude that there is no solid evidence for
      direct molecular interaction of Src with Na(+)/K(+)-ATPase under physiological
      conditions. 

PMID- 24667597
TI  - Rv1027c-Rv1028c encode functional KdpDE two--component system in Mycobacterium
      tuberculosis.
AB  - In Mycobacteriumtuberculosis Rv1027c-Rv1028c genes are predicted to encode KdpDE
      two component system, which is highly conserved across all bacterial species.
      Here, we show that the system is functionally active and KdpD sensor kinase
      undergoes autophosphorylation and transfers phosphoryl group to KdpE, response
      regulator protein. We identified His(642) and Asp(52) as conserved
      phosphorylation sites in KdpD and KdpE respectively and by SPR analysis confirmed
      the physical interaction between them. KdpD was purified with prebound divalent
      ions and their importance in phosphorylation was established using protein
      refolding and ion chelation approaches. Genetically a single transcript encoded
      both KdpD and KdpE proteins. Overall, we report that M. tuberculosis KdpDE system
      operates like a canonical two component system. 

PMID- 24667598
TI  - New insights into the location and form of sclerostin.
AB  - Sclerostin is widely reported to be a monomeric osteocyte specific protein. In
      this study we have investigated whether sclerostin is produced in different forms
      and in which cell and tissue types they are produced. We have demonstrated that
      recombinant sclerostin is composed of monomers and dimers, and that these, and
      other forms, notably 46 and 70 kDa forms, are found widely throughout the musculo
      skeletal system. We have shown that 'dimeric' sclerostin is highly resistant to
      reduction, implying the presence of highly stable, non-reducible covalent bonds.
      We have also demonstrated that the form of sclerostin is not associated with the
      mineralisation state of the tissue or cell. Sclerostin was secreted by bone
      explants as high molecular weight forms that were reducible to the dimeric form.
      This dimeric form was detected in sera and in non-skeletal soft tissues
      specifically kidney, live, heart and lung. We therefore hypothesise: (a)
      sclerostin exists in multiple forms not associated with the mineralised state of
      the cell/tissue and (b) circulating sclerostin is dimeric, as is the sclerostin
      found in non-musculoskeletal soft tissues. These observations may have
      significant implications for the therapeutic modulation of sclerostin.

PMID- 24667599
TI  - Adaptation to acrolein through upregulating the protection by glutathione in
      human bronchial epithelial cells: the materialization of the hormesis concept.
AB  - Acrolein is a thiol reactive compound present in cigarette smoke and plays a
      pivotal role in the deleterious effects of smoking. Acrolein causes toxicity in
      human bronchial epithelial cells in a dose dependent manner. GSH forms the first
      line of defense against acrolein-induced toxicity. At high doses of acrolein (?10
      MUM) the capacity of the cellular protection by GSH is overwhelmed and GSH is not
      able to quench all the acrolein, resulting in cytotoxicity. At a relatively low
      dose of acrolein (3 MUM), no cytotoxicity is observed due to protection by GSH.
      Moreover we found that exposure to a low dose of acrolein protects cells against
      the toxic effect of a second higher dose of acrolein. The adaptation to acrolein
      is induced via Nrf2 mediated gene expression of gamma-glutamylcysteine synthetase
      leading to elevated GSH levels. This upregulation of the protection by GSH
      demonstrates a hormetic response to acrolein. Hormesis is an adaptive or
      compensatory response induced by a relatively subtle challenge of homeostasis by
      a toxic compound. Insight into the mechanism of hormesis is mandatory for a more
      accurate societal regulation of toxic compounds.

PMID- 24667600
TI  - The Mycobacterium tuberculosis transcriptional repressor EthR is negatively
      regulated by Serine/Threonine phosphorylation.
AB  - Recent efforts have underlined the role of Serine/Threonine Protein Kinases
      (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein,
      we demonstrated that the Mycobacterium tuberculosis EthR, a transcriptional
      repressor that regulates the activation process of the antitubercular drug
      ethionamide (ETH) is a specific substrate of the mycobacterial kinase PknF. ETH
      is a prodrug that must undergo bioactivation by the monooxygenease EthA to exert
      its antimycobacterial activity and previous studies reported that EthR represses
      transcription of ethA by binding to the ethA-ethR intergenic region. Mass
      spectrometry analyses and site-directed mutagenesis identified a set of four
      phosphoacceptors, namely Thr2, Thr3, Ser4 and Ser7. This was further supported by
      the complete loss of PknF-dependent phosphorylation of a phosphoablative EthR
      mutant protein. Importantly, a phosphomimetic version of EthR, in which all
      phosphosites were replaced by Asp residues, exhibited markedly decreased DNA
      binding activity compared with the wild-type protein. Together, these findings
      are the first demonstration of EthR phosphorylation and indicate that
      phosphorylation negatively affects its DNA-binding activity, which may impact ETH
      resistance levels in M. tb. 

PMID- 24667601
TI  - Mouse liver lysosomes contain enzymatically active processed forms of Hyal-1.
AB  - It has long been known that liver lysosomes contain an endoglycosidase activity
      able to degrade the high molecular mass glycosaminoglycan hyaluronic acid (HA).
      The identification and cloning of a hyaluronidase with an acidic pH optimum, Hyal
      1, suggested it might be responsible for this activity. However, we previously
      reported that this hydrolase could only be detected in pre-lysosomal compartments
      of the mouse liver using a zymography technique that allows the detection of Hyal
      1 activity after SDS-PAGE ("renatured protein zymography"). Present work reveals
      that the activity highlighted by this technique belongs to a precursor form of
      Hyal-1 and that the lysosomal HA endoglycosidase activity of the mouse liver is
      accounted for by a proteolytically processed form of Hyal-1 that can only be
      detected using "native protein zymography". Indeed, the distribution of this form
      follows the distribution of beta-galactosidase, a well-established lysosomal
      marker, after fractionation of the mouse liver in a linear sucrose density
      gradient. In addition, both activities shift toward the lower density region of
      the gradient when a specific decrease of the lysosomal density is induced by
      Triton WR-1339 injection. The fact that only native protein zymography but not
      renatured protein zymography is able to detect Hyal-1 activity in lysosomes
      points to a non-covalent association of Hyal-1 proteolytic fragments or the
      existence of closely linked partners supporting Hyal-1 enzymatic activity. The
      knockdown of Hyal-1 results in an 80% decrease of total acid hyaluronidase
      activity in the mouse liver, confirming that Hyal-1 is a key actor of HA
      catabolism in this organ. 

PMID- 24667602
TI  - Radiation increases the cellular uptake of exosomes through CD29/CD81 complex
      formation.
AB  - Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or
      their secreted exosomes affect a number of pathophysiologic states. Clinical
      applications of MSC and exosomes are increasingly anticipated. Radiation therapy
      is the main therapeutic tool for a number of various conditions. The cellular
      uptake mechanisms of exosomes and the effects of radiation on exosome-cell
      interactions are crucial, but they are not well understood. Here we examined the
      basic mechanisms and effects of radiation on exosome uptake processes in MSC.
      Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced
      the initial cellular attachment to exosomes and induced the colocalization of
      integrin CD29 and tetraspanin CD81 on the cell surface without affecting their
      expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown
      of CD29 completely inhibited the radiation-induced uptake, and additional or
      single knockdown of CD81 inhibited basal uptake as well as the increase in
      radiation-induced uptake. We also examined possible exosome uptake processes
      affected by radiation. Radiation-induced changes did not involve dynamin2,
      reactive oxygen species, or their evoked p38 mitogen-activated protein kinase
      dependent endocytic or pinocytic pathways. Radiation increased the cellular
      uptake of exosomes through CD29/CD81 complex formation. These findings provide
      essential basic insights for potential therapeutic applications of exosomes or
      MSC in combination with radiation. 

PMID- 24667603
TI  - Protein kinase Cdelta contributes to phenylephrine-mediated contraction in the
      aortae of high fat diet-induced obese mice.
AB  - The down-regulation of alpha-adrenoceptor-mediated signaling casacade has been
      implicated in obesity but the underlying mechanism remains largely unknown. The
      present study investigated whether inositol 1,4,5-trisphosphate (IP3) receptor
      and protein kinase C (PKC) were involved in the reduction of alpha1-adrenoceptor
      agonist phenylephrine-evoked contraction in aortae of high fat diet-induced obese
      (DIO) mice. C57BL/6 mice were fed with a rodent diet containing 45 kcal% fat for
      16 weeks to induce obesity. Isolated mouse aortae were suspended in myograph for
      isometric force measurement. Protein phosphorylations and expressions were
      determined by Western blotting. In C57BL/6 mouse aortae, phenylephrine-induced
      contraction was partially inhibited by either IP3 receptor antagonist heparin or
      PKC inhibitor GFX, and the combined treatment with heparin and GFX abolished the
      contraction. Phenylephrine-induced contraction was significantly less in the
      aortae of DIO mice than those of control mice; only GFX but not heparin
      attenuated the contraction, indicating a diminishing role of IP3 receptor in DIO
      mice. Western blotting showed the reduced expression and phosphorylation of IP3
      receptor and the down-regulated expression of PKC, PKCbeta, PKCdelta, and PKCzeta
      in DIO mouse aortae. Importantly, PKCdelta was more likely to maintain
      phenylephrine-mediated contraction in DIO mouse aortae because that (1) PKCdelta
      inhibitor rottlerin but not PKCalpha and PKCbeta inhibitor Go6976, PKCbeta
      inhibitor hispidin, or PKCzeta pseudosubstrate inhibitor attenuated the
      contraction; and (2) PKCdelta phosphorylation was increased but phosphorylations
      of PKCalpha, PKCbeta, and PKCzeta were reduced in DIO mouse aortae. The present
      study thus provides additional insights into the cellular mechanisms responsible
      for vascular dysfunction in obesity.

PMID- 24667604
TI  - Role of MERIT40 in stabilization of BRCA1 complex: a protein-protein interaction
      study.
AB  - MERIT40 is a novel associate of the BRCA1-complex, thus play an essential role in
      DNA damage repair mechanism. It is the least implicit protein and its structural
      and functional aspects of regulating the stability of BRCA1-MERIT40 complex
      remain equivocal. Analysis of protein-protein interactions between BRCA1 and its
      cellular binding partners like ABRAXAS, RAP80 and MERIT40 would help to
      understand the role of protein complex integrity in DNA repair mechanism. The
      recombinant proteins were purified and their structural aspects were elucidated
      by spectroscopic methods. Interaction analysis was carried out to determine
      binding partners of MERIT40. MERIT40 showed interaction with bridging molecule,
      called ABRAXAS, thus generate a scaffold among various members which further
      stabilizes the entire complex. It acts as an adapter molecule by interacting with
      BRCA1-BRCT in non-phosphorylation dependent manner. The feature enlighten on
      structural and interaction profile of BRCA1-complex member to elucidate their
      role in complex stability and DNA repair process. 

PMID- 24667606
TI  - Targeted repression of AXIN2 and MYC gene expression using designer TALEs.
AB  - Designer TALEs (dTALEs) are chimeric transcription factors that can be engineered
      to regulate gene expression in mammalian cells. Whether dTALEs can block gene
      transcription downstream of signal transduction cascades, however, has yet to be
      fully explored. Here we tested whether dTALEs can be used to target genes whose
      expression is controlled by Wnt/beta-catenin signaling. TALE DNA binding domains
      were engineered to recognize sequences adjacent to Wnt responsive enhancer
      elements (WREs) that control expression of axis inhibition protein 2 (AXIN2) and
      c-MYC (MYC). These custom DNA binding domains were linked to the mSin3A
      interaction domain (SID) to generate TALE-SID chimeric repressors. The TALE-SIDs
      repressed luciferase reporter activity, bound their genomic target sites, and
      repressed AXIN2 and MYC expression in HEK293 cells. We generated a novel HEK293
      cell line to determine whether the TALE-SIDs could function downstream of
      oncogenic Wnt/beta-catenin signaling. Treating these cells with doxycycline and
      tamoxifen stimulates nuclear accumulation of a stabilized form of beta-catenin
      found in a subset of colorectal cancers. The TALE-SIDs repressed AXIN2 and MYC
      expression in these cells, which suggests that dTALEs could offer an effective
      therapeutic strategy for the treatment of colorectal cancer. 

PMID- 24667605
TI  - PTK2b function during fertilization of the mouse oocyte.
AB  - Fertilization triggers rapid changes in intracellular free calcium that serve to
      activate multiple signaling events critical to the initiation of successful
      development. Among the pathways downstream of the fertilization-induced calcium
      transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or
      PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish
      oocyte and the objective of the present study was to establish whether PTK2b also
      functions in mammalian fertilization. PTK2b was activated during the first few
      hours after fertilization of the mouse oocyte during the period when anaphase
      resumption was underway and prior to the pronuclear stage. Suppression of PTK2b
      kinase activity in oocytes blocked sperm incorporation and egg activation
      although sperm-oocyte binding was not affected. Oocytes that failed to
      incorporate sperm after inhibitor treatment showed no evidence of a calcium
      transient and no evidence of anaphase resumption suggesting that egg activation
      did not occur. The results indicate that PTK2b functions during the sperm-egg
      fusion process or during the physical incorporation of sperm into the egg
      cytoplasm and is therefore critical for successful development. 

PMID- 24667607
TI  - Basic Tilted Helix Bundle - a new protein fold in human FKBP25/FKBP3 and HectD1.
AB  - In this paper, we describe the structure of a N-terminal domain motif in nuclear
      localized FKBP251-73, a member of the FKBP family, together with the structure of
      a sequence-related subdomain of the E3 ubiquitin ligase HectD1 that we show
      belongs to the same fold. This motif adopts a compact 5-helix bundle which we
      name the Basic Tilted Helix Bundle (BTHB) domain. A positively charged surface
      patch, structurally centered around the tilted helix H4, is present in both
      FKBP25 and HectD1 and is conserved in both proteins, suggesting a conserved
      functional role. We provide detailed comparative analysis of the structures of
      the two proteins and their sequence similarities, and analysis of the interaction
      of the proposed FKBP25 binding protein YY1. We suggest that the basic motif in
      BTHB is involved in the observed DNA binding of FKBP25, and that the function of
      this domain can be affected by regulatory YY1 binding and/or interactions with
      adjacent domains.

PMID- 24667608
TI  - Resistin regulates the expression of plasminogen activator inhibitor-1 in 3T3-L1
      adipocytes.
AB  - Resistin and plasminogen activator inhibitor-1 (PAI-1) are adipokines, which are
      secreted from adipocytes. Increased plasma resistin and PAI-1 levels aggravate
      metabolic syndrome through exacerbation of insulin resistance and induction of
      chronic inflammation. However, the relationship between resistin and PAI-1 gene
      expression remains unclear. Previously, we found that resistin regulates lipid
      metabolism via carbohydrate responsive element-binding protein (ChREBP) during
      adipocyte maturation (Ikeda et al., 2013) [6]. In this study, to clarify the
      relationship between expression of resistin and PAI-1, PAI-1 expression in
      differentiated 3T3-L1 adipocytes was measured after transfection with anti
      resistin siRNA. We found that PAI-1 gene expression and secreted PAI-1 protein
      were significantly decreased by resistin knockdown. Furthermore, phosphorylation
      of Akt, which can inhibit PAI-1 expression, was accelerated and the activity of
      protein phosphatase 2A (PP2A) was suppressed in resistin knockdown 3T3-L1
      adipocytes. In addition, the expression of glucose transporter type 4, a ChREBP
      target gene, was reduced and was associated with inhibition of PP2A. The addition
      of culture medium collected from COS7 cells transfected with a resistin
      expression plasmid rescued the suppression of PAI-1 expression in resistin
      knockdown 3T3-L1 adipocytes. Our findings suggest that resistin regulates PAI-1
      expression in 3T3-L1 adipocytes via Akt phosphorylation. 

PMID- 24667609
TI  - Extended effect of chronic social defeat stress in childhood on behaviors in
      adulthood.
AB  - Individuals exposed to social stress in childhood are more predisposed to
      developing psychoemotional disorders in adulthood. Here we use an animal model to
      determine the influence of hostile social environment in adolescence on behavior
      during adult life. One-month-old adolescent male mice were placed for 2 weeks in
      a common cage with an adult aggressive male. Animals were separated by a
      transparent perforated partition, but the adolescent male was exposed daily to
      short attacks from the adult male. After exposure to social stress, some of the
      adolescent mice were placed for 3 weeks in comfortable conditions. Following this
      rest period, stressed young males and adult males were studied in a range of
      behavioral tests to evaluate the levels of anxiety, depressiveness, and
      communicativeness with an unfamiliar partner. In addition, adult mice exposed to
      social stress in adolescence were engaged in agonistic interactions. We found
      that 2 weeks of social stress result in a decrease of communicativeness in the
      home cage and diminished social interactions on the novel territory. Stressed
      adolescents demonstrated a high level of anxiety in the elevated plus-maze test
      and helplessness in the Porsolt test. Furthermore, the number of dividing (BrdU
      positive) cells in the subgranular zone of the dentate gyrus was significantly
      lower in stressed adolescents. After 3 weeks of rest, most behavioral
      characteristics in different tests, as well as the number of BrdU-positive cells
      in the hippocampus, did not differ from those of the respective control mice.
      However, the level of anxiety remained high in adult males exposed to chronic
      social stress in childhood. Furthermore, these males were more aggressive in the
      agonistic interactions. Thus, hostile social environment in adolescence disturbs
      psychoemotional state and social behaviors of animals in adult life. 

PMID- 24667610
TI  - Elevated tissue plasminogen activator and reduced plasminogen activator inhibitor
      promote hyperfibrinolysis in trauma patients.
AB  - Severe hyperfibrinolysis after trauma is a poorly understood phenomenon
      associated with profound shock, serious anatomic injuries, increased
      transfusions, and high mortality rates. Molecular mechanisms driving
      hyperfibrinolysis in trauma have not been completely delineated. The authors
      aimed to determine the relationship between severe hyperfibrinolysis and outcomes
      in trauma patients and characterize the role of the plasminogen activator (PA)
      system in this condition. A prospective observational study was performed in 163
      adult level I trauma patients admitted between April and August 2012. Blood was
      collected on admission, and fibrinolysis was determined by plasmin-alpha2
      antiplasmin (PAP) levels. Tissue-derived and urokinase PA (tPA and uPA,
      respectively), PA inhibitor (PAI-1), fibrinogen, and antithrombin levels were
      also measured. Patient demographics, vital signs, laboratory values, mechanisms
      and severity of injuries, transfusions, and outcomes were collected at admission
      or from patient records. Moderate fibrinolysis was defined as PAP level 1,500 to
      20,000 MUg/L and severe hyperfibrinolysis as PAP level more than 20,000 MUg/L.
      Severe hyperfibrinolysis was observed in 10% of patients and associated with
      increased injury severity, greater transfusions, fewer ventilator and hospital
      free days, and higher mortality. Plasmin-alpha2 antiplasmin level was directly
      correlated with tPA level and inversely correlated with PAI-1 level. Patients
      with both elevated tPA and reduced PAI-1 were more severely injured, received
      more transfusions, and experienced fewer ventilator and hospital-free days. In
      conclusion, Severe hyperfibrinolysis is observed in a small percentage of trauma
      patients and is associated with severe injuries, greater transfusions, and worse
      outcomes. This condition is mediated, in part, by excessive upregulation of
      profibrinolytic tPA in the absence of concomitant increases in antifibrinolytic
      PAI-1. 

PMID- 24667611
TI  - Influence of early dysnatremia correction on survival of critically ill patients.
AB  - Increasing evidence suggests that dysnatremia at intensive care unit (ICU)
      admission may predict mortality. Little information is available, however, on the
      potential effect of dysnatremia correction. This is an observational multicenter
      cohort study in patients admitted between 2005 and 2012 to 18 French ICUs.
      Hyponatremia and hypernatremia were defined as serum sodium concentration less
      than 135 and more than 145 mmol/L, respectively. We assessed the influence on day
      28 mortality of dysnatremia correction by day 3 and of the dysnatremia correction
      rate. Of 7,067 included patients, 1,830 (25.9%) had hyponatremia and 634 (9.0%)
      had hypernatremia at ICU admission (day 1). By day 3, hyponatremia had been
      corrected in 1,019 (1,019/1,830; 55.7%) and hypernatremia in 393 (393/634; 62.0%)
      patients. After adjustment for confounders, persistent hyponatremia or
      hypernatremia on day 3 was independently associated with higher day 28 mortality
      (odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.06 - 1.61; and OR,
      1.86; 95% CI, 1.37 - 2.54; respectively). Hyponatremia corrected by day 3,
      hypernatremia corrected by day 3, and ICU-acquired hyponatremia were not
      associated with day 28 mortality. Median correction rate from days 1 to 3 was
      2.58 mmol/L per day (interquartile range, 0.67 - 4.55). Higher natremia
      correction rate was associated with lower crude and adjusted day 28 mortality
      rates (OR per mmol/L per day, 0.97; 95% CI, 0.94 - 1.00; P = 0.04; and OR per
      mmol/L per day, 0.93; 95% CI, 0.90 - 0.97; P = 0.0003, respectively). Our results
      indicate that dysnatremia correction is independently associated with survival,
      with the effect being greater with faster correction rates of up to 12 mmol/L per
      day. 

PMID- 24667613
TI  - Influence of arterial dissolved oxygen level on venous oxygen saturation: don't
      forget the PaO2!
AB  - Dissolved oxygen (i.e., unbound to hemoglobin) is often neglected as a
      determinant of central venous oxygen saturation (ScvO2) in review articles and
      textbooks. These statements may lead to potential misinterpretation of SCvO2
      value across FiO2 changes. In this study, we aimed to explore the influence of
      PaO2 and FiO2 on ScvO2 in ventilated critically ill patients. This was a
      prospective observational study in two surgical intensive care units.
      Mechanically ventilated and sedated patients with cardiac output and ScvO2
      monitoring and PaO2/FiO2 > 200 with inspiratory oxygen (FiO2) <= 0.5 were
      enrolled (cohort [ScvO2]). A second cohort of brain-injured patients with jugular
      venous oxygen saturation monitoring was studied to assess the application of the
      results to regional circulation (cohort [SjvO2]). Central venous oxygen
      saturation was measured at baseline FiO2 and at FiO2 = 1. We finally estimated
      the participation of the dissolved oxygen (PadissolvO2) to the ScvO2 variations.
      Twenty patients formed the cohort ScvO2 and eight formed the cohort SjvO2.
      Central venous oxygen saturation rose from 71% (69%-76%) to 84% (78%-88%) after
      increasing FiO2, whereas PaO2 rose from 100 (85-124) mmHg to 387 (360-449) mmHg.
      The rise of ScvO2 was mostly ascribable to the dissolved oxygen. The increase of
      ScvO2 was not explained by changes in cardiac output or hemoglobin levels.
      Jugular venous oxygen saturation rose from 71% (58%-78%) to 83% (78%-89%) after
      increasing FiO2. Arterial dissolved oxygen level can significantly influence the
      ScvO2 value. Therefore, PaO2 should not be overlooked while considering the ScvO2
      value as a therapeutic goal. Interpretation of ScvO2 variations in response to a
      therapeutic challenge (i.e., fluid challenge, inotropic drug initiation) should
      be performed at constant FiO2. 

PMID- 24667612
TI  - Effect of deletion of cIAP2 on intestinal microcirculation in mouse endotoxemia
      and polybacterial sepsis.
AB  - Deletion of the cellular inhibitor of apoptosis protein 2 (cIAP2) is capable of
      rendering lipopolysaccharide (LPS)-activated macrophages highly susceptible to
      apoptotic triggers, thereby quickly eliminating the resident macrophage
      population soon after the initiation of a systemic inflammatory response. The aim
      of our study was to evaluate the impact of cIAP2 deletion on leukocyte
      recruitment and capillary perfusion in experimental endotoxemia and polybacterial
      sepsis using intravital microscopy of the intestinal microcirculation, which is
      crucial in the pathogenesis of septic multiple organ failure. We studied six
      groups of animals: wild-type (WT) control mice, cIAP2 knockout mice, endotoxemic
      WT mice (5 mg/kg LPS), endotoxemic cIAP2 knockouts (5 or 50 mg/kg LPS,
      respectively), and WT as well as knockout mice with polybacterial sepsis (colon
      ascendens stent peritonitis [CASP]). Intravital microscopy of the intestinal
      microcirculation was performed after 1 h of endotoxemia or 12 h of CASP-induced
      sepsis, respectively. Intestinal microvascular blood flow was measured using
      laser Doppler flowmetry. After 1 h of endotoxemia (5 mg/kg LPS), we observed a
      significant increase of leukocyte adhesion in intestinal submucosal venules of WT
      mice in comparison with control animals. The cIAP2 knockout mice showed a
      significant reduction in leukocyte recruitment within the intestinal submucosal
      microvasculature after 5 or 50 mg/kg LPS challenge, respectively.
      Lipopolysaccharide-induced decrease in intestinal microvascular blood flow was
      not affected by cIAP2 inhibition. In CASP-induced sepsis, cIAP2 deletion had no
      effect on intestinal leukocyte recruitment. Deletion of cIAP2 resulted in reduced
      microvascular leukocyte recruitment within the intestinal microcirculation in
      endotoxemia but not in polybacterial sepsis. 

PMID- 24667614
TI  - Establishment of methods for performing thrombelastography and calibrated
      automated thrombography in rats.
AB  - Rodent models of hemorrhagic shock are paramount to our understanding of the
      pathophysiology of this disease, the effects on coagulation and in exploring the
      utility of resuscitative methods for managing patients in shock. These models
      usually require serial blood sampling during experimentation. The lack of
      standardized practices for these experimental models has resulted in technical
      variability, discordance in the literature, and incomparable results on blood
      coagulation analysis between researchers, hindering substantial progress in the
      field of hemorrhagic shock. The aim of this study was to define the effects of
      cardiac puncture versus arterial catheterization on coagulation in a rat model to
      provide data supporting standardization of one practice over another. Blood was
      collected from anesthetized rats via cardiac puncture or femoral artery
      catheterization and hemostatic potential analyzed by thrombelastography and
      calibrated automated thrombography. Our data show that blood collected via
      cardiac puncture demonstrated hypercoagulability as indicated by faster rates of
      clot formation and thrombin generation, increased overall clot strength, and a
      greater thrombin-generating capacity when compared with blood collected via
      femoral artery catheter. We conclude that blood collection methods have a
      profound effect on hemostatic potential, and standardization of these practices
      is necessary to define the effects of shock on coagulation in rodents. 

PMID- 24667615
TI  - Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain
      injury.
AB  - Danger-associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins
      that are released from the injured tissues and activate the innate immune system.
      Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular
      milieu subsequent to cell death and injury. We hypothesized that cell death
      within the central nervous system in children with traumatic brain injury (TBI)
      would lead to the release of mtDNA into the cerebrospinal fluid (CSF) and has the
      potential to predict the outcome after trauma. Cerebrospinal fluid was collected
      from children with severe TBI who required intracranial pressure monitoring with
      Glasgow Coma Scale (GCS) scores of 8 or less via an externalized ventricular
      drain. Control CSF was obtained in children without TBI or meningoencephalitis
      who demonstrated no leukocytes in the diagnostic lumbar puncture. The median age
      for patients with TBI was 6.3 years, and 62% were male. The common mechanisms of
      injury included motor vehicle collision (35.8%), followed by falls (21.5%) and
      inflicted TBI (19%); six children (14.2%) died during their intensive care unit
      course. The mean CSF mtDNA concentration was 1.10E+05 +/- 2.07E+05 and 1.63E+03
      +/- 1.80E+03 copies/MUL in the pediatric TBI and control populations,
      respectively. Furthermore, the mean CSF mtDNA concentration in pediatric patients
      who later died or had severe disability was significantly higher than that of the
      survivors (1.63E+05 +/- 2.77E+05 vs. 5.05E+04 +/- 6.21E+04 copies/MUL) (P <
      0.0001). We found a significant correlation between CSF mtDNA and high mobility
      group box 1, another prototypical DAMP, concentrations (rho = 0.574, P < 0.05),
      supporting the notion that both DAMPs are increased in the CSF after TBI. Our
      data suggest that CSF mtDNA is a novel DAMP in TBI and appears to be a useful
      biomarker that correlates with neurological outcome after TBI. Further inquiry
      into the components of mtDNA that modulate the innate immune response will be
      helpful in understanding the mechanism of local and systemic inflammation after
      TBI. 

PMID- 24667616
TI  - Muramyl dipeptide enhances thermal injury-induced inflammatory cytokine
      production and organ function injury in rats.
AB  - The bacterial infection following thermal injury is a very important factor of
      excessive inflammatory response and multiple organ damage. Muramyl dipeptide
      (MDP) is the key structure of gram-positive bacteria and gram-negative bacteria
      triggering the innate immune system. The aim of the present study was to
      determine the effect of MDP on thermal injury-induced inflammatory responses,
      organ function injury, and mortality in rats. Fifty male Sprague-Dawlay rats were
      randomly divided into three groups: normal control group, scald group, and MDP
      group. Scald group only suffered 20% total body surface area third-degree thermal
      injury. Muramyl dipeptide 5 mg.kg was administered through the femoral vein at 24
      h after thermal injury in the MDP group. Plasma inflammatory cytokine levels were
      measured by enzyme-linked immunosorbent assay. An additional 90 male Sprague
      Dawley rats were randomly divided into three groups to observe the survival rate
      in 72 h. Plasma levels of interleukin-6, interleukin-10, interferon-gamma, and
      high-mobility group box 1; the white blood cell counts; the serum concentrations
      of alanine aminotransferase, aspartate aminotransferase, total bilirubin,
      creatine kinase isoenzyme-MB, blood urea nitrogen, and creatinine; and the
      activity of lung tissue myeloperoxidase significantly increased after thermal
      injury alone. Compared with the scald group, MDP led to more serious inflammatory
      responses and organ function damage and higher mortality (P < 0.05,
      respectively). These data indicate that MDP exacerbates thermal injury-induced
      inflammatory cytokine production, accompanied by multiple organ dysfunction
      syndrome and high mortality in rats. 

PMID- 24667617
TI  - TLR2 deficiency aggravates lung injury caused by mechanical ventilation.
AB  - Innate immunity pathways are found to play an important role in ventilator
      induced lung injury. We analyzed pulmonary expression of Toll-like receptor 2
      (TLR2) in humans and mice and determined the role of TLR2 in the pathogenesis of
      ventilator-induced lung injury in mice. Toll-like receptor 2 gene expression was
      analyzed in human bronchoalveolar lavage fluid (BALF) cells and murine lung
      tissue after 5 h of ventilation. In addition, wild-type (WT) and TLR2 knockout
      (KO) mice were ventilated with either lower tidal volumes (VT) of 7 mL/kg with
      positive end-expiratory pressure (PEEP) or higher VT of 15 mL/kg without PEEP for
      5 h. Spontaneously breathing mice served as controls. Total protein and
      immunoglobulin M levels in BALF, neutrophil influx into the alveolar compartment,
      and interleukin 6 (IL-6), IL-1beta, and keratinocyte-derived chemokine
      concentrations in lung tissue homogenates were measured. We observed enhanced
      TLR2 gene expression in BALF cells of ventilated patients and in lung tissue of
      ventilated mice. In WT mice, ventilation with higher VT without PEEP resulted in
      lung injury and inflammation with higher immunoglobulin M levels, neutrophil
      influx, and levels of inflammatory mediators compared with controls. In TLR2 KO
      mice, neutrophil influx and IL-6, IL-1beta, and keratinocyte-derived chemokine
      were enhanced by this ventilation strategy. Ventilation with lower VT with PEEP
      only increased neutrophil influx and was similar in WT and TLR2 KO mice. In
      summary, injurious ventilation enhances TLR2 expression in lungs. Toll-like
      receptor 2 deficiency does not protect lungs from ventilator-induced lung injury.
      In contrast, ventilation with higher VT without PEEP aggravates inflammation in
      TLR2 KO mice. 

PMID- 24667618
TI  - Expression of hemopexin in acute rejection of rat liver allograft identified by
      serum proteomic analysis.
AB  - Acute rejection (AR) and acceptance of allograft after liver transplantation
      (LTx) remain critical issues that need addressing to improve prognosis. We
      therefore performed rat orthotopic LTx and proteomic analyses to screen for
      immune response-related biomarkers in sera. Markers identified were validated at
      the mRNA and/or protein levels, and the molecules of interest were functionally
      explored. Compared with syngeneic controls, signs of AR as well as spontaneous
      acceptance were observed in hematoxylin and eosin-stained sections of liver
      allografts. In accordance with the severity of AR, 30 protein spots displaying
      significant changes in abundance were identified using two-dimensional
      differential gel electrophoresis. Ultimately, 14 serum proteins were sequenced
      and five spots of interest were identified as hemopexin (HPX). Expression of HPX
      was significantly and inversely associated with the severity of AR at both the
      mRNA and protein levels. In vitro, Mt-1, Ho-1, Fth, Ifn-gamma, and Il-17
      transcripts were significantly upregulated in lysates of lymphocytes stimulated
      with HPX, whereas Il-10 markedly was remarkably downregulated. Interferon-gamma,
      IL-10, and IL-17 proteins in the supernatant of HPX-stimulated lymphocytes were
      significantly altered in keeping with the mRNA level. Our data facilitated the
      generation of a proteomic profile to enhance the understanding of rat liver AR.
      In view of finding that the HPX serum level is negatively associated with the
      severity of AR of rat liver allograft, we propose that in vitro treatment with
      HPX regulates cytokine expression in rat lymphocytes. 

PMID- 24667619
TI  - Significant sex-based outcome differences in severely injured Chinese trauma
      patients.
AB  - A body of experimental evidence suggests that the female sex is associated with a
      lower risk of mortality after trauma-hemorrhage. However, controversy remains
      regarding the mechanism responsible for these differences and if basic science
      findings correspond to clinical differences. Racial disparities in trauma
      outcomes have also been increasingly described. Until now, research on the
      association between sex and trauma patient outcomes mainly focused on patients in
      Europe and the United States. Our research attempted to determine whether the
      female sex is associated with a survival advantage among severely injured Chinese
      trauma patients. A retrospective analysis of data derived from the Emergency
      Intensive Care Unit of the Shanghai Sixth People';s Hospital Acute Trauma Center
      during 2010 to 2013 was performed to characterize differences in sex-based
      outcomes after severe blunt trauma. The patient study cohort (858 Asian subjects)
      was then stratified by age and injury severity (using the Injury Severity Score
      [ISS]). Crude and adjusted odds ratios (ORs) were calculated to evaluate the
      association between sex and nosocomial infection rate and hospitalized mortality,
      both overall and by age and ISS category subgroups. Among all trauma patients,
      females had a significantly lower risk of in-hospital mortality compared with
      males (OR, 0.41; 95% confidence interval [95% CI], 0.20 - 0.85). This difference
      was most apparent for patients younger than 50 years (OR, 0.31; 95% CI, 0.12 -
      0.82) and the group with ISS scores of 25 or higher (OR, 0.39; 95% CI, 0.17 -
      0.91). No differences in the development of nosocomial infections between sexes
      were seen among the overall patient group and subgroups. This study revealed a
      statistically significant association between sex and mortality among severe
      blunt trauma patients, particularly those patients younger than 50 years and with
      ISSs of 25 or higher. Women had significantly lower mortality than men after
      severe blunt trauma. These results highlight the important role of sex hormones
      and sex-based outcome differences after severe traumatic injury in the Chinese
      population. 

PMID- 24667620
TI  - Adrenocorticotropic hormone but not high-density lipoprotein cholesterol or
      salivary cortisol was a predictor of adrenal insufficiency in patients with
      septic shock.
AB  - Relative adrenal insufficiency in sepsis has been extensively debated on;
      however, accurate diagnosis and therapeutic intervention remain controversial.
      The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary
      cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and
      lipoproteins as predictors of adrenal insufficiency in patients within 24 h of
      septic shock diagnosis. This prospective study evaluated all hospitalized
      patients older than 18 years who developed septic shock and were using vasoactive
      drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline
      and 60 min (T60) after 250 MUg tetracosactide intravenous injection. Patients
      were divided into two groups: responders (Delta [T60 minus baseline] total
      cortisol >9 MUg/dL) and nonresponders (Delta total cortisol <= 9 MUg/dL or
      baseline total cortisol <10 MUg/dL). The latter group was considered to have
      adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and
      34 subjects with septic shock were included in the analysis. Adrenal
      insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein
      cholesterol, triglycerides, and salivary cortisol did not differ between groups.
      Estimated plasma-free cortisol was not better than total plasma cortisol in
      estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders
      than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff
      ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL.
      Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could
      predict adrenal response to tetracosactide.

PMID- 24667621
TI  - Role of alveolar macrophages in the inflammatory response after trauma.
AB  - Acute lung injury (ALI) and its more severe form, acute respiratory distress
      syndrome (ARDS), can result from both direct and indirect pulmonary damage caused
      by trauma and shock. In the course of ALI/ARDS, mediators released from resident
      cells, such as alveolar macrophages, may act as chemoattractants for invading
      cells and stimulate local cells to build up a proinflammatory micromilieu.
      Depending on the trauma setting, the role of alveolar macrophages is
      differentially defined. This review focuses on alveolar macrophage function after
      blunt chest trauma, ischemia/reperfusion, hemorrhagic shock, and thermal burns. 

PMID- 24667622
TI  - Identification of potential biomarkers by serum proteomics analysis in rats with
      sepsis.
AB  - This study was aimed to find new biomarkers for diagnosis and prediction of
      prognosis of sepsis. Serum samples from nonsurvivor, survivor, and control groups
      were obtained at 12 h after the induction of sepsis and labeled with isobaric
      tags (iTRAQ) and then analyzed by two-dimensional liquid chromatography and
      tandem mass spectrometry. Protein identification and quantification were obtained
      using mass spectrometry and the ProteinPilot software. Bioinformatics annotation
      was performed by searching against the PANTHER database. Enzyme-linked
      immunosorbent assays were used to further confirm the protein identification and
      differential expression. A logistic regression was then used to screen the index
      set for diagnosis and prognosis of sepsis. We found that 47 proteins were
      preferentially elevated in septic rats (both nonsurvivors and survivors) compared
      with the control rats, and 28 proteins were preferentially elevated in the NS
      rats as compared with the S group. Several biomarkers, such as multimerin 1,
      ficolin 1, carboxypeptidase N (CPN2), serine protease 1, and platelet factor 4,
      were tightly correlated with the diagnosis of sepsis. Logistic regression
      analyses established multimerin 1, pro-platelet basic protein, fibrinogen-alpha,
      and fibrinogen-beta for prognosis of sepsis. 

PMID- 24667624
TI  - Investigation of noninvasive muscle pH and oxygen saturation during uncontrolled
      hemorrhage and resuscitation in swine.
AB  - This study evaluated noninvasively determined muscle pH (pHm) and muscle oxygen
      saturation (SmO2) in a swine shock model that used uncontrolled hemorrhage and
      restricted volume resuscitation. Anesthetized 40-kg female swine underwent
      hemorrhage until 24 mL/kg of blood was removed (n = 26), followed by transection
      of the spleen, causing uncontrolled hemorrhage throughout the remainder of the
      protocol. After 15 min, 15 mL/kg of resuscitation fluid (Hextend, fresh-frozen
      plasma or platelets) was given for 30 min. Arterial and venous blood gases were
      measured at baseline, shock, end of resuscitation, and end of the study (death or
      5 h), along with lactate and base excess. In addition, seven animals underwent a
      sham procedure. Spectra were collected continuously from the posterior thigh
      using a prototype CareGuide 1100 Oximeter, and pHm and SmO2 were calculated from
      the spectra. A two-factor analysis of variance with repeated measures followed by
      Tukey post hoc comparisons was used to compare experimental factors. It was shown
      that, for both pH and SO2, venous and muscle values were similar to each other at
      the end of the resuscitation period and at the end of the study for both
      surviving and nonsurviving animals. pH and SO2, venous and muscle, significantly
      declined as a result of bleeding, but lactate and base excess did not show
      significant changes during this period. Noninvasive pHm and SmO2 tracked the
      adequacy of resuscitation in real time, indicating at the time all of the fluid
      was delivered, which animals would live and which would die. The results of this
      swine study indicate that further evaluation on trauma patients is warranted. 

PMID- 24667623
TI  - Gamma delta T cells regulate wound myeloid cell activity after burn.
AB  - Major burns induce immune complications, which are associated with myeloid cell
      activation by ill-defined mechanisms. Although gammadelta T cells have been shown
      to be important in postinjury inflammation and wound healing, their role in the
      regulation of myeloid cells remains unknown. To study this, wild-type (WT) and
      gammadelta T cell-deficient (deltaTCR) mice were subjected to major burn (25%
      total body surface area, third degree) or sham treatment. At 3 days thereafter,
      skin samples were assayed for cytokine content or used to isolate single cells
      that were used for myeloid cell characterization by flow cytometry. The number of
      CD11b myeloid cells increased by approximately 75% in the wound skin of WT mice.
      This influx was caused by increased myeloid-derived suppressor cells (CD11b GR1)
      whose numbers increased 19-fold compared with those of sham skin. In contrast,
      macrophage (MO; CD11b F4/80) numbers decreased by approximately 50% after burn.
      In deltaTCR mice, burn increased the myeloid cell numbers approximately 5-fold.
      The increase in myeloid cells at the injury site of deltaTCR mice was caused by
      both a myeloid-derived suppressor cell (50-fold) and a MO (2-fold) influx. Burn
      increased skin cytokine levels for a number of prototypic inflammatory cytokines
      (interleukin 1beta, interleukin 6, tumor necrosis factor-alpha, macrophage
      inflammatory protein [MIP] 1beta, etc). Tumor necrosis factor-alpha, MIP-1alpha,
      and MIP-1beta levels were further elevated (2- to 3-fold) in the injured skin of
      deltaTCR mice compared with those of WT mice. In conclusion, these data show that
      gammadelta T cells regulate myeloid cell infiltration of the wound site and act
      to quell inflammation, thereby promoting the transition to the proliferative
      phase of wound healing. 

PMID- 24667625
TI  - Endotoxin tolerance drives neutrophil to infectious site.
AB  - The objective of this randomized animal study and laboratory investigation was to
      investigate whether lipopolysaccharide tolerance redirects neutrophil migration
      between organs. Male BALB/c mice received subcutaneous injections of
      lipopolysaccharide (1 mg/kg) for 5 days, followed by cecal ligation and puncture
      (CLP). Cytokines and adhesion molecules were measured after tolerance and CLP
      challenge. Increased numbers of neutrophils were observed in the peritoneal
      cavity of tolerant mice, which was associated with increased levels of adhesion
      molecules and chemokines. In contrast, nontolerant mice accumulated higher
      numbers of neutrophils in the lungs compared with those in the peritoneal cavity.
      Neutrophil function accessed by hydrogen peroxide production from neutrophils
      recovered from peritoneal cavity showed that tolerance increased the capacity to
      produce hydrogen peroxide. Mortality was reduced in tolerant animals. This study
      demonstrated that tolerance reduces leukocyte accumulation in the lung after CLP
      by redirecting neutrophils to the site of infection. 

PMID- 24667626
TI  - The noninvasive carbon dioxide gradient (NICO2G) during hemorrhagic shock.
AB  - Hemorrhagic shock (HS) is a setting in which both pulmonary and cutaneous
      perfusion may be impaired. The goals of this study were to evaluate the
      relationship between end-tidal (etCO2), transcutaneous (tPCO2), arterial carbon
      dioxide (PaCO2) and lactate during lethal HS and to assess the effect of
      progressive HS on those variables and on a new variable, the noninvasive CO2
      gradient ([NICO2G] or the difference between tPCO2 and etCO2). Ten consciously
      sedated swine were hemorrhaged, by means of a computerized exponential protocol,
      of up to 80% estimated blood volume for 20 min. End-tidal carbon dioxide, tPCO2,
      PaCO2, and lactate measurements were taken at baseline and every 5 min
      thereafter, that is, after 25%, 44%, and 62% total blood volume hemorrhage (TBVH)
      and at cardiac arrest. Cardiac arrest occurred on average at 67% TBVH. Data were
      analyzed by linear regression and one-way repeated-measures analysis of variance
      and are presented as means +/- SD. Forty-nine paired measurements were made.
      There was no overall relationship between NICO2 variables and PaCO2: PaCO2 vs.
      tPCO2 (r2 = 0.002, P = 0.78); PaCO2 vs. etCO2 (r2 = 0.0002, P = 0.93). Rather,
      NICO2G increased at each level of blood loss: 4.0 +/- 24.9 at baseline, 6.3 +/-
      35.7 at 25% TBVH, 25.0 +/- 37.6 at 44% TBVH, 55.0 +/- 33.9 at 62% TBVH, and 70.0
      +/- 33.2 at cardiac arrest (P < 0.05). Similarly, tPCO2 increased and etCO2
      decreased at each level. Linear regression of NICO2G and lactate showed a better
      correlation than was observed for the other two variables: NICO2G, r2 = 0.58;
      tPCO2, r2 = 0.46; etCO2, r2 = 0.26. During HS, NICO2 monitors lose accuracy for
      approximating the PaCO2 but gain usefulness as hemodynamic monitors. Also, by
      combining data from two different organ systems, NICO2G demonstrated improved
      correlation with lactate than did either etCO2 or tPCO2 alone.

PMID- 24667627
TI  - Oxygen challenge test in septic shock patients: prognostic value and influence of
      respiratory status.
AB  - Transcutaneous oxygen pressure (PtcO2) value in response to an increase of FiO2
      or oxygen challenge test (OCT) in ventilated patients has been reported to be
      related to peripheral perfusion and outcome during septic shock. However,
      patients with sepsis-related acute respiratory distress syndrome could
      demonstrate compromised arterial oxygenation with OCT impairment decoupled to
      circulatory failure. The aims of this study were to confirm the prognostic value
      of OCT and to explore the influence of respiratory status on OCT results. This
      was a prospective study set in an intensive care unit of a tertiary teaching
      hospital. Fifty-six mechanically ventilated patients with septic shock criteria
      were studied. Transcutaneous oxygen pressure was measured at baseline and after
      OCT, at intensive care unit admittance (T0), and 24 h later (T24). Survival at
      day 28 and hemodynamic and respiratory parameters were analyzed and compared
      according to outcome and respiratory status. Central hemodynamic parameters or
      static transcutaneous data did not differ between survivors and nonsurvivors at
      enrollment. The OCT was statistically different at T24 according to outcome (P <
      0.001), but sensitivity was low (53%). Moreover, patients with low OCT results at
      T24 exhibited more severe respiratory failure (P < 0.01). The OCT at T24 is
      related to outcome but is influenced by the severity of respiratory failure. Our
      results suggest considering with caution hemodynamic management based on OCT in
      septic shock patients with altered pulmonary function. 

PMID- 24667628
TI  - The value of noninvasive measurement of the compensatory reserve index in
      monitoring and triage of patients experiencing minimal blood loss.
AB  - Currently available triage and monitoring tools are often late to detect life
      threatening clinically significant physiological aberrations and provide limited
      data in prioritizing bleeding patients for treatment and evacuation. The
      Compensatory Reserve Index (CRI) is a novel means of assessing physiologic
      reserve, shown to correlate with central blood volume loss under laboratory
      conditions. The purpose of this study was to compare the noninvasive CRI device
      with currently available vital signs in detecting blood loss. Study subjects were
      soldiers volunteering for blood donation (n = 230), and the control group was
      composed of soldiers who did not donate blood (n = 34). Data collected before and
      after blood donation were compared, receiver operator characteristic curves were
      generated after either donation or the appropriate time interval, and areas under
      the curves (AUCs) were compared. Compared with pre-blood loss, blood donation
      resulted in a mean reduction of systolic blood pressure by 3% (before, 123 mmHg;
      after, 119 mmHg; P < 0.01). The CRI demonstrated a 16% reduction (before, 0.74;
      after, 0.62; P < 0.01). Heart rate, diastolic blood pressure, and oxygen
      saturation remained unchanged. The AUC for change in CRI was 0.81, 0.56 for
      change in heart rate, 0.53 for change in systolic blood pressure, 0.55 and 0.58
      for pulse pressure and shock index, respectively. The AUCs for detecting mild
      blood loss at a single measurement were 0.73 for heart rate, 0.60 for systolic
      blood pressure, 0.62 for diastolic blood pressure, 0.45 for pulse oximetry, and
      0.84 for CRI. The CRI was better than standard indices in detecting mild blood
      loss. Single measurement of CRI may enable a more accurate triage, and CRI
      monitoring may allow for earlier detection of casualty deterioration. 

PMID- 24667629
TI  - Caffeic acid phenethyl ester (CAPE): scavenger of peroxynitrite in vitro and in
      sepsis models.
AB  - Excessive free radical production by immune cells has been linked to cell death
      and tissue injury during sepsis. Peroxynitrite is a short-lived oxidant and a
      potent inducer of cell death that has been identified in several pathological
      conditions. Caffeic acid phenethyl ester (CAPE) is an active component of
      honeybee products and exhibits antioxidant, anti-inflammatory, and
      immunomodulatory activities. The present study examined the ability of CAPE to
      scavenge peroxynitrite in RAW 264.7 murine macrophages stimulated with
      lipopolysaccharide/interferon-gamma that was used as an in vitro model.
      Conversion of 123-dihydrorhodamine to its oxidation product 123-rhodamine was
      used to measure peroxynitrite production. Two mouse models of sepsis (endotoxemia
      and cecal ligation and puncture) were used as in vivo models. The level of serum
      3-nitrotyrosine was used as an in vivo marker of peroxynitrite. The results
      demonstrated that CAPE significantly improved the viability of
      lipopolysaccharide/interferon-gamma-treated RAW 264.7 cells and significantly
      inhibited nitric oxide production, with effects similar to those observed with an
      inhibitor of inducible nitric oxide synthase (1400W). In addition, CAPE
      exclusively inhibited the synthesis of peroxynitrite from the artificial
      substrate SIN-1 and directly prevented the peroxynitrite-mediated conversion of
      dihydrorhodamine-123 to its fluorescent oxidation product rhodamine-123. In both
      sepsis models, CAPE inhibited cellular peroxynitrite synthesis, as evidenced by
      the absence of serum 3-nitrotyrosine, an in vivo marker of peroxynitrite. Thus,
      CAPE attenuates the inflammatory responses that lead to cell damage and,
      potentially, cell death through suppression of the production of cytotoxic
      molecules such as nitric oxide and peroxynitrite. These observations provide
      evidence of the therapeutic potential of CAPE treatment for a wide range of
      inflammatory disorders. 

PMID- 24667631
TI  - The effects of super-flux (high performance) dialyzer on plasma glycosylated pro
      B-type natriuretic peptide (proBNP) and glycosylated N-Terminal proBNP in end
      stage renal disease patients on dialysis.
AB  - BACKGROUND: Plasma BNP levels are predictive of prognosis in hemodialysis
      patients. However, recent studies showed that the current BNP immunoassay cross
      reacts with glycosylated proBNP, and the NT-proBNP assay underestimates
      glycosylated NT-proBNP. In addition, the recently developed high performance
      dialyzer removes medium-sized molecular solutes such as beta2-microgloburin. We
      therefore investigated the effects of high performance dialysis on measured
      levels of glycosylated proBNP, glycosylated NT-proBNP and other BNP-related
      peptides in end-stage renal disease (ESRD) patients on hemodialysis. METHOD: The
      relationships between clinical parameters and BNP-related molecule were also
      investigated. We used our newly developed immunoassay to measure plasma total BNP
      and proBNP in 105 normal subjects and 36 ESRD patients before and after
      hemodialysis. Plasma NT-proBNP was measured using Elecsys II after treatment with
      or without deglycosylating enzymes. We also measured plasma ANP and cGMP using
      radioimmunoassays. RESULTS: All the measured BNP-related peptides were
      significantly higher in ESRD patients than healthy subjects. Total BNP (-38.9%),
      proBNP (-29.7%), glycoNT-proBNP (-45.5%), nonglycoNT-proBNP (-53.4%), ANP (
      50.4%) and cGMP (-72.1%) were all significantly reduced after hemodialysis, and
      the magnitude of the reduction appeared molecular weight- dependent. Both the
      proBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios were increased after
      hemodialysis. The former correlated positively with hemodialysis vintage and
      negatively with systolic blood pressure, while the latter correlated positively
      with parathyroid hormone levels. CONCLUSION: These results suggest that
      hemodialysis using super-flux dialyzer removes BNP-related peptides in a nearly
      molecular weight-dependent manner. The ProBNP/total BNP and glycoNT
      proBNP/nonglycoNT-proBNP ratios appear to be influenced by hemodialysis-related
      parameters in ESRD patients on hemodialysis.

PMID- 24667630
TI  - Itraconazole, a commonly used antifungal, inhibits Fcgamma receptor-mediated
      phagocytosis: alteration of Fcgamma receptor glycosylation and gene expression.
AB  - Itraconazole (ICZ) is commonly used for the treatment of fungal infections,
      particularly in immunocompromised patients. In addition, ICZ has been recently
      found to have antiangiogenic effects and is currently being tested as a new
      chemotherapeutic agent in several cancer clinical trials. We have previously
      shown that ICZ impaired complex N-linked glycosylation processing, leading to the
      accumulation of high-mannose glycoproteins on the surface of macrophages (Mos).
      This investigation was directed at determining the effects of ICZ on phagocytosis
      as a major function of Mos. We found a significant decrease in the phagocytosis
      of opsonized bacterial particles in ICZ-treated murine Mos in comparison with
      nontreated Mos. Furthermore, the impairment of phagocytosis was associated with a
      decrease in cell surface expression of Fcgamma receptors (FcgammaRs) as well as
      alteration of their glycosylation pattern. Concomitantly, a reduction in all
      three isoforms of the FcgammaR family (i.e., Fcgr1, Fcgr2, and Fcgr3) mRNA levels
      was observed after incubation with ICZ. The effect of ICZ on phagocytosis and
      FcgammaR expression was reversed by addition of low-density lipoprotein. These
      studies indicate that ICZ treatment certainly has a dramatic effect on macrophage
      function, which could result in a potential impairment of the immune system';s
      ability to respond to pathogens and may lead to an elevated incidence of
      infections. 

PMID- 24667632
TI  - How insect flight steering muscles work.
AB  - Insights into how exactly a fly powers and controls flight have been hindered by
      the need to unpick the dynamic complexity of the muscles involved. The wingbeats
      of insects are driven by two antagonistic groups of power muscles and the force
      is funneled to the wing via a very complex hinge mechanism. The hinge consists of
      several hardened and articulated cuticle elements called sclerites. This
      articulation is controlled by a great number of small steering muscles, whose
      function has been studied by means of kinematics and muscle activity. The details
      and partly novel function of some of these steering muscles and their tendons
      have now been revealed in research published in this issue of PLOS Biology. The
      new study from Graham Taylor and colleagues applies time-resolved X-ray
      microtomography to obtain a three-dimensional view of the blowfly wingbeat.
      Asymmetric power output is achieved by differential wingbeat amplitude on the
      left and right wing, which is mediated by muscular control of the hinge elements
      to mechanically block the wing stroke and by absorption of work by steering
      muscles on one of the sides. This new approach permits visualization of the
      motion of the thorax, wing muscles, and the hinge mechanism. This very promising
      line of work will help to reveal the complete picture of the flight motor of a
      fly. It also holds great potential for novel bio-inspired designs of fly-like
      micro air vehicles. 

PMID- 24667633
TI  - Idiopathic hypereosinophilic syndrome with multiple organ infarction: improvement
      of the skin condition masking the course of disease.

PMID- 24667634
TI  - Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human
      plasma after a single dose of long-chain omega-3 PUFA.
AB  - INTRODUCTION: Several supplementation studies with long-chain omega-3
      polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived
      hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of
      other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate
      the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion,
      we conducted a single dose treatment study with healthy subjects. SUBJECTS AND
      METHODS: In the present kinetic study, we compared patterns of hydroxy, epoxy and
      dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and
      48h of fish oil (1008mg EPA and 672mg DHA) ingestion. Levels of EPA- as well as
      other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in
      plasma by LC-MS. Additionally, levels of these oxylipins were compared with their
      parent PUFA levels in plasma phospholipids. RESULTS: All EPA-derived oxylipin
      levels were significantly increased 6h after LC n-3 PUFA ingestion and gradually
      drop thereafter reaching the baseline levels about 48h after treatment. The
      relative increase in EPA plasma phospholipid levels highly correlated with the
      increase of plasma EPA-derived oxylipin levels at different time points. In
      contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as
      parent PUFA levels in plasma phospholipids were hardly changed. DISCUSSION AND
      CONCLUSIONS: Our findings demonstrate that a single dose of LC n-3 PUFAs can
      rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a
      few hours. Taking the high biological activity of the EPA-derived epoxy fatty
      acids into account, even short-term treatment with LC n-3 PUFAs may cause
      systemic effects, which warrant further investigation.

PMID- 24667635
TI  - RIP140 increases APC expression and controls intestinal homeostasis and
      tumorigenesis.
AB  - Deregulation of the Wnt/APC/beta-catenin signaling pathway is an important
      consequence of tumor suppressor APC dysfunction. Genetic and molecular data have
      established that disruption of this pathway contributes to the development of
      colorectal cancer. Here, we demonstrate that the transcriptional coregulator
      RIP140 regulates intestinal homeostasis and tumorigenesis. Using Rip140-null mice
      and mice overexpressing human RIP140, we found that RIP140 inhibited intestinal
      epithelial cell proliferation and apoptosis. Interestingly, following whole-body
      irradiation, mice lacking RIP140 exhibited improved regenerative capacity in the
      intestine, while mice overexpressing RIP140 displayed reduced recovery. Enhanced
      RIP140 expression strongly repressed human colon cancer cell proliferation in
      vitro and after grafting onto nude mice. Moreover, in murine tissues and human
      cancer cells, RIP140 stimulated APC transcription and inhibited beta-catenin
      activation and target gene expression. Finally, RIP140 mRNA and RIP140 protein
      levels were decreased in human colon cancers compared with those in normal
      mucosal tissue, and low levels of RIP140 expression in adenocarcinomas from
      patients correlated with poor prognosis. Together, these results support a tumor
      suppressor role for RIP140 in colon cancer. 

PMID- 24667636
TI  - Leptin-promoted cilia assembly is critical for normal energy balance.
AB  - The majority of mammalian cells have nonmotile primary cilia on their surface
      that act as antenna-like sensory organelles. Genetic defects that result in
      ciliary dysfunction are associated with obesity in humans and rodents, which
      suggests that functional cilia are important for controlling energy balance. Here
      we demonstrated that neuronal cilia lengths were selectively reduced in
      hypothalami of obese mice with leptin deficiency and leptin resistance. Treatment
      of N1 hypothalamic neuron cells with leptin stimulated cilia assembly via
      inhibition of the tumor suppressors PTEN and glycogen synthase kinase 3beta
      (GSK3beta). Induction of short cilia in the hypothalamus of adult mice increased
      food intake and decreased energy expenditure, leading to a positive energy
      balance. Moreover, mice with short hypothalamic cilia exhibited attenuated
      anorectic responses to leptin, insulin, and glucose, which indicates that leptin
      induced cilia assembly is essential for sensing these satiety signals by
      hypothalamic neurons. These data suggest that leptin governs the sensitivity of
      hypothalamic neurons to metabolic signals by controlling the length of the cell's
      antenna. 

PMID- 24667637
TI  - Methyltransferase G9A regulates T cell differentiation during murine intestinal
      inflammation.
AB  - Inflammatory bowel disease (IBD) pathogenesis is associated with dysregulated
      CD4+ Th cell responses, with intestinal homeostasis depending on the balance
      between IL-17-producing Th17 and Foxp3+ Tregs. Differentiation of naive T cells
      into Th17 and Treg subsets is associated with specific gene expression profiles;
      however, the contribution of epigenetic mechanisms to controlling Th17 and Treg
      differentiation remains unclear. Using a murine T cell transfer model of colitis,
      we found that T cell-intrinsic expression of the histone lysine methyltransferase
      G9A was required for development of pathogenic T cells and intestinal
      inflammation. G9A-mediated dimethylation of histone H3 lysine 9 (H3K9me2)
      restricted Th17 and Treg differentiation in vitro and in vivo. H3K9me2 was found
      at high levels in naive Th cells and was lost following Th cell activation. Loss
      of G9A in naive T cells was associated with increased chromatin accessibility and
      heightened sensitivity to TGF-beta1. Pharmacological inhibition of G9A
      methyltransferase activity in WT T cells promoted Th17 and Treg differentiation.
      Our data indicate that G9A-dependent H3K9me2 is a homeostatic epigenetic
      checkpoint that regulates Th17 and Treg responses by limiting chromatin
      accessibility and TGF-beta1 responsiveness, suggesting G9A as a therapeutic
      target for treating intestinal inflammation.

PMID- 24667639
TI  - Development of a conditionally immortalized human pancreatic beta cell line.
AB  - Diabetic patients exhibit a reduction in beta cells, which secrete insulin to
      help regulate glucose homeostasis; however, little is known about the factors
      that regulate proliferation of these cells in human pancreas. Access to primary
      human beta cells is limited and a challenge for both functional studies and drug
      discovery progress. We previously reported the generation of a human beta cell
      line (EndoC-betaH1) that was generated from human fetal pancreas by targeted
      oncogenesis followed by in vivo cell differentiation in mice. EndoC-betaH1 cells
      display many functional properties of adult beta cells, including expression of
      beta cell markers and insulin secretion following glucose stimulation; however,
      unlike primary beta cells, EndoC-betaH1 cells continuously proliferate. Here, we
      devised a strategy to generate conditionally immortalized human beta cell lines
      based on Cre-mediated excision of the immortalizing transgenes. The resulting
      cell line (EndoC-betaH2) could be massively amplified in vitro. After expansion,
      transgenes were efficiently excised upon Cre expression, leading to an arrest of
      cell proliferation and pronounced enhancement of beta cell-specific features such
      as insulin expression, content, and secretion. Our data indicate that excised
      EndoC-betaH2 cells are highly representative of human beta cells and should be a
      valuable tool for further analysis of human beta cells. 

PMID- 24667638
TI  - Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites
      in vivo.
AB  - Activation of the GPCR sphingosine-1-phosphate receptor 1 (S1P1) by sphingosine-1
      phosphate (S1P) regulates key physiological processes. S1P1 activation also has
      been implicated in pathologic processes, including autoimmunity and inflammation;
      however, the in vivo sites of S1P1 activation under normal and disease conditions
      are unclear. Here, we describe the development of a mouse model that allows in
      vivo evaluation of S1P1 activation. These mice, known as S1P1 GFP signaling mice,
      produce a S1P1 fusion protein containing a transcription factor linked by a
      protease cleavage site at the C terminus as well as a beta-arrestin/protease
      fusion protein. Activated S1P1 recruits the beta-arrestin/protease, resulting in
      the release of the transcription factor, which stimulates the expression of a GFP
      reporter gene. Under normal conditions, S1P1 was activated in endothelial cells
      of lymphoid tissues and in cells in the marginal zone of the spleen, while
      administration of an S1P1 agonist promoted S1P1 activation in endothelial cells
      and hepatocytes. In S1P1 GFP signaling mice, LPS-mediated systemic inflammation
      activated S1P1 in endothelial cells and hepatocytes via hematopoietically derived
      S1P. These data demonstrate that S1P1 GFP signaling mice can be used to evaluate
      S1P1 activation and S1P1-active compounds in vivo. Furthermore, this strategy
      could be potentially applied to any GPCR to identify sites of receptor activation
      during normal physiology and disease. 

PMID- 24667640
TI  - CaMK4-dependent activation of AKT/mTOR and CREM-alpha underlies autoimmunity
      associated Th17 imbalance.
AB  - Tissue inflammation in several autoimmune diseases, including SLE and MS, has
      been linked to an imbalance of IL-17-producing Th (Th17) cells and Tregs;
      however, the factors that promote Th17-driven autoimmunity are unclear. Here, we
      present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4)
      is increased and required during Th17 cell differentiation. Isolation of naive T
      cells from a murine model of lupus revealed increased levels of CaMK4 following
      stimulation with Th17-inducing cytokines but not following Treg, Th1, or Th2
      induction. Furthermore, naive T cells from mice lacking CaMK4 did not produce IL
      17. Genetic or pharmacologic inhibition of CaMK4 decreased the frequency of IL-17
      producing T cells and ameliorated EAE and lupus-like disease in murine models.
      Inhibition of CaMK4 reduced Il17 transcription through decreased activation of
      the cAMP response element modulator alpha (CREM-alpha) and reduced activation of
      the AKT/mTOR pathway, which is known to enhance Th17 differentiation.
      Importantly, silencing CaMK4 in T cells from patients with SLE and healthy
      individuals inhibited Th17 differentiation through reduction of IL17A and IL17F
      mRNA. Collectively, our results suggest that CaMK4 inhibition has potential as a
      therapeutic strategy for Th17-driven autoimmune diseases. 

PMID- 24667641
TI  - PD-1 identifies the patient-specific CD8+ tumor-reactive repertoire infiltrating
      human tumors.
AB  - Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression
      of metastatic melanoma; however, TILs are a heterogeneous population, and there
      are no effective markers to specifically identify and select the repertoire of
      tumor-reactive and mutation-specific CD8+ lymphocytes. The lack of biomarkers
      limits the ability to study these cells and develop strategies to enhance
      clinical efficacy and extend this therapy to other malignancies. Here, we
      evaluated unique phenotypic traits of CD8+ TILs and TCR beta chain (TCRbeta)
      clonotypic frequency in melanoma tumors to identify patient-specific repertoires
      of tumor-reactive CD8+ lymphocytes. In all 6 tumors studied, expression of the
      inhibitory receptors programmed cell death 1 (PD-1; also known as CD279),
      lymphocyte-activation gene 3 (LAG-3; also known as CD223), and T cell
      immunoglobulin and mucin domain 3 (TIM-3) on CD8+ TILs identified the autologous
      tumor-reactive repertoire, including mutated neoantigen-specific CD8+
      lymphocytes, whereas only a fraction of the tumor-reactive population expressed
      the costimulatory receptor 4-1BB (also known as CD137). TCRbeta deep sequencing
      revealed oligoclonal expansion of specific TCRbeta clonotypes in CD8+PD-1+
      compared with CD8+PD-1- TIL populations. Furthermore, the most highly expanded
      TCRbeta clonotypes in the CD8+ and the CD8+PD-1+ populations recognized the
      autologous tumor and included clonotypes targeting mutated antigens. Thus, in
      addition to the well-documented negative regulatory role of PD-1 in T cells, our
      findings demonstrate that PD-1 expression on CD8+ TILs also accurately identifies
      the repertoire of clonally expanded tumor-reactive cells and reveal a dual
      importance of PD-1 expression in the tumor microenvironment.

PMID- 24667642
TI  - An optimized and simplified system of mouse embryonic stem cell cardiac
      differentiation for the assessment of differentiation modifiers.
AB  - Generating cardiomyocytes from embryonic stem cells is an important technique for
      understanding cardiovascular development, the origins of cardiovascular diseases
      and also for providing potential reagents for cardiac repair. Numerous methods
      have been published but often are technically challenging, complex, and are not
      easily adapted to assessment of specific gene contributions to cardiac myocyte
      differentiation. Here we report the development of an optimized protocol to
      induce the differentiation of mouse embryonic stem cells to cardiac myocytes that
      is simplified and easily adapted for genetic studies. Specifically, we made four
      critical findings that distinguish our protocol: 1) mouse embryonic stem cells
      cultured in media containing CHIR99021 and PD0325901 to maintain pluripotency
      will efficiently form embryoid bodies containing precardiac mesoderm when
      cultured in these factors at a reduced dosage, 2) low serum conditions promote
      cardiomyocyte differentiation and can be used in place of commercially prepared
      StemPro nutrient supplement, 3) the Wnt inhibitor Dkk-1 is dispensable for
      efficient cardiac differentiation and 4) tracking differentiation efficiency may
      be done with surface expression of PDGFRalpha alone. In addition, cardiac
      mesodermal precursors generated by this system can undergo lentiviral infection
      to manipulate the expression of specific target molecules to assess effects on
      cardiac myocyte differentiation and maturation. Using this approach, we assessed
      the effects of CHF1/Hey2 on cardiac myocyte differentiation, using both gain and
      loss of function. Overexpression of CHF1/Hey2 at the cardiac mesoderm stage had
      no apparent effect on cardiac differentiation, while knockdown of CHF1/Hey2
      resulted in increased expression of atrial natriuretic factor and connexin 43,
      suggesting an alteration in the phenotype of the cardiomyocytes. In summary we
      have generated a detailed and simplified protocol for generating cardiomyocytes
      from mES cells that is optimized for investigating factors that affect cardiac
      differentiation. 

PMID- 24667643
TI  - Acoustic behavior of microbubbles and implications for drug delivery.
AB  - Ultrasound contrast agents are valuable in diagnostic ultrasound imaging, and
      they increasingly show potential for drug delivery. This review focuses on the
      acoustic behavior of flexible-coated microbubbles and rigid-coated microcapsules
      and their contribution to enhanced drug delivery. Phenomena relevant to drug
      delivery, such as non-spherical oscillations, shear stress, microstreaming, and
      jetting will be reviewed from both a theoretical and experimental perspective.
      Further, the two systems for drug delivery, co-administration and the microbubble
      as drug carrier system, are reviewed in relation to the microbubble behavior.
      Finally, future prospects are discussed that need to be addressed for ultrasound
      contrast agents to move from a pre-clinical tool into a clinical setting. 

PMID- 24667644
TI  - Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a
      platform for personalised medicine.
AB  - BACKGROUND: Challenges in developing drugs for pancreatic ductal adenocarcinoma
      (PDAC) include obtaining metastatic cancer tissue for research and validating
      biomarkers predicative for personalised therapeutic decisions. We have recently
      developed a novel therapeutic model for PDAC to address these challenges based on
      the isolation of viable PDAC cells derived from ascites fluid. METHODS: Ascites
      fluid was obtained from PDAC patients undergoing palliative paracentesis. Ascites
      derived PDAC primary cells were isolated, cultured and characterised in ovo and
      in vitro. RESULTS: We successfully established ascites-derived primary cell
      cultures within 2-7 days from 92% (93 out of 101) of the ascites fluid samples
      obtained (from 36 different patients). Homogeneous epithelial PDAC-enriched cell
      cultures were identified and characterised. We observed a wide range in doubling
      times and migration properties among the different patient-derived cell cultures.
      The diverse nature of each individual patient's cell cultures was further
      demonstrated by differences in therapeutic susceptibility and resistance. The
      tumorigenicity and invasiveness of the cells were demonstrated in vivo using
      chicken chorioallantoic membrane grafts. CONCLUSIONS: We have developed a unique
      ascites-derived PDAC primary cell culture model. This model has the potential to
      study signalling pathways in PDAC progression and to evaluate targeted therapies
      for the individual patient expeditiously, thereby supporting personalised
      treatment decisions.

PMID- 24667645
TI  - Identification of high-risk patients with clear cell renal cell carcinoma based
      on interphase-FISH.
AB  - BACKGROUND: The aim of this study was to examine the prognostic value of four
      significant aberrations based on our previous studies by array-CGH to develop a
      prognostic Fluorescence-in situ-hybridisation (FISH) assay for clear cell renal
      cell carcinomas (ccRCC). METHODS: Fluorescence-in situ-hybridisation experiments
      were performed on 100 ccRCCs (52 metastasised out of 48 non-metastasised). The
      mean/median follow up of patients was 59/54 months. Commercially available FISH
      probes were used for each critical chromosomal region (1q21.3, 7q36.3,
      9p21.3p24.1 and 20q11.21q13.32). The total number of specific aberrations (TNSA)
      was calculated for each tumour based on the specific genomic alterations.
      RESULTS: Total number of specific aberrations was the best predictor of
      metastasis (area under the curve (AUC)=0.814) compared with single aberrations
      (AUC: 0.619-0.708) and to 11 different combinations of these 4 aberrations in the
      receiver operating characteristic curve analysis. Total number of specific
      aberrations, tumour grade and tumour size were independent predictors of
      metastasis in the multivariate analysis (P<0.001) for the whole cohort as well as
      for organ-confined tumours. Total number of specific aberrations and grade could
      also independently predict cancer-specific mortality (CSM). Total number of
      specific aberrations demonstrated the highest significance in COX proportional
      hazard models of overall survival (OS), cancer-specific survival (CSS) and
      progression-free survival (PFS). CONCLUSIONS: We identified TNSA as an
      independent prognostic factor which is associated with metastasis occurrence,
      CSM, OS, CSS and PFS in patients with ccRCCs.

PMID- 24667646
TI  - Cholecystectomy, gallstones, tonsillectomy, and pancreatic cancer risk: a
      population-based case-control study in Minnesota.
AB  - BACKGROUND: Associations between medical conditions and pancreatic cancer risk
      are controversial and are thus evaluated in a study conducted during 1994-1998 in
      Minnesota. METHODS: Cases (n=215) were ascertained from hospitals in the
      metropolitan area of the Twin Cities and the Mayo Clinic. Controls (n=676) were
      randomly selected from the general population and frequency matched to cases by
      age and sex. The history of medical conditions was gathered with a questionnaire
      during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95%
      CI) were estimated using unconditional logistic regression. RESULTS: After
      adjustment for confounders, subjects who had cholecystectomy or gallstones
      experienced a significantly higher risk of pancreatic cancer than those who did
      not (OR (95% CI): 2.11 (1.32-3.35) for cholecystectomy and 1.97 (1.23-3.12) for
      gallstones), whereas opposite results were observed for tonsillectomy (0.67 (0.48
      0.94)). Increased risk associated with cholecystectomy was the greatest when it
      occurred <= 2 years before the cancer diagnosis (5.93 (2.36-15.7)) but remained
      statistically significant when that interval was >= 20 years (2.27 (1.16-4.32)).
      CONCLUSIONS: Cholecystectomy, gallstones, and tonsillectomy were associated with
      an altered risk of pancreatic cancer. Our study suggests that cholecystectomy
      increased risk but reverse causality may partially account for high risk
      associated with recent cholecystectomy.

PMID- 24667647
TI  - Biological significance of fluorine-18-alpha-methyltyrosine (FAMT) uptake on PET
      in patients with oesophageal cancer.
AB  - PURPOSE: (18)F-FAMT as an amino-acid tracer for positron emission tomography
      (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in
      tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was
      conducted to investigate the biological significance of (18)F-FAMT uptake in
      patients with oesophageal cancer. METHODS: From April 2008 to December 2011, 42
      patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG
      PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98,
      Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro
      experiments were performed to examine the mechanism of (18)F-FAMT uptake.
      RESULTS: High uptake of (18)F-FAMT was significantly associated with advanced
      stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34.
      LAT1 expression yielded a statistically significant correlation with CD98
      expression, cell proliferation, angiogenesis and glucose metabolism. In vitro
      experiments revealed that (18)F-FAMT was specifically transported by LAT1.
      CONCLUSIONS: The uptake of (18)F-FAMT within tumour cells is determined by the
      LAT1 expression and correlated with cell proliferation and angiogenesis in
      oesophageal cancer. The present experiments also confirmed the presence of LAT1
      as an underlying mechanism of (18)F-FAMT accumulation.

PMID- 24667648
TI  - Prognostic performance of inflammation-based prognostic indices in primary
      operable non-small cell lung cancer.
AB  - BACKGROUND: At least 30% of patients with primary resectable non-small cell lung
      cancer (NSCLC) will experience a relapse in their disease within 5 years
      following definitive treatment. Clinicopathological predictors have proved to be
      suboptimal in identifying high-risk patients. We aimed to establish whether
      inflammation-based scores offer an improved prognostic ability in terms of
      estimating overall (OS) and recurrence-free survival (RFS) in a cohort of
      operable, early-stage NSCLC patients. METHODS: Clinicopathological, demographic
      and treatment data were collected prospectively for 220 patients operated for
      primary NSCLC at the Hammersmith Hospital from 2004 to 2011. Pretreatment
      modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR)
      and platelet-to-lymphocyte ratio (PLR) were tested together with established
      prognostic factors in uni- and multivariate Cox regression analyses of OS and
      RFS. RESULTS: Half of the patients were male, with a median age of 65. A total of
      57% were classified as stage I with adenocarcinoma being the most prevalent
      subtype (60%). Univariate analyses of survival revealed stage (P<0.001), grade
      (P=0.02), lymphovascular (LVI, P=0.001), visceral pleural invasion (VPI,
      P=0.003), mGPS (P=0.02) and NLR (P=0.04) as predictors of OS, with stage
      (P<0.001), VPI (P=0.02) and NLR (P=0.002) being confirmed as independent
      prognostic factors on multivariate analyses. Patients with more advanced stage
      (P<0.001) and LVI (P=0.008) had significantly shorter RFS. CONCLUSIONS: An
      elevated NLR identifies operable NSCLC patients with a poor prognostic outlook
      and an OS difference of almost 2 years compared to those with a normal score at
      diagnosis. Our study validates the clinical utility of the NLR in early-stage
      NSCLC.

PMID- 24667649
TI  - Higher dietary folate intake reduces the breast cancer risk: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Many epidemiological studies have investigated the association
      between folate intake, circulating folate level and risk of breast cancer;
      however, the findings were inconsistent between the studies. METHODS: We searched
      the PubMed and MEDLINE databases updated to January, 2014 and performed the
      systematic review and meta-analysis of the published epidemiological studies to
      assess the associations between folate intake level, circulating folate level and
      the overall risk of breast cancer. RESULTS: In all, 16 eligible prospective
      studies with a total of 744 068 participants and 26 205 breast cancer patients
      and 26 case-control studies with a total of 16 826 cases and 21 820 controls that
      have evaluated the association between folate intake and breast cancer risk were
      identified. Pooled analysis of the prospective studies and case-control studies
      suggested a potential nonlinearity relationship for dietary folate intake and
      breast cancer risk. Prospective studies indicated a U-shaped relationship for the
      dietary folate intake and breast cancer risk. Women with daily dietary folate
      intake between 153 and 400 MUg showed a significant reduced breast cancer risk
      compared with those <153 MUg, but not for those >400 MUg. The case-control
      studies also suggested a significantly negative correlation between the dietary
      folate intake level and the breast cancer risk. Increased dietary folate intake
      reduced breast cancer risk for women with higher alcohol intake level, but not
      for those with lower alcohol intake. No significant association between
      circulating folate level and breast cancer risk was found when the results of 8
      identified studies with 5924 participants were pooled. CONCLUSIONS: Our studies
      suggested that folate may have preventive effects against breast cancer risk,
      especially for those with higher alcohol consumption level; however, the dose and
      timing are critical and more studies are warranted to further elucidate the
      questions.

PMID- 24667651
TI  - Adaptive designs for clinical trials assessing biomarker-guided treatment
      strategies.
AB  - BACKGROUND: The Biomarker Strategy Design has been proposed for trials assessing
      the value of a biomarker in guiding treatment in oncology. In such trials,
      patients are randomised to either receive the standard chemotherapy treatment or
      a biomarker-directed treatment arm, in which biomarker status is used to guide
      treatment. METHODS: Motivated by a current trial, we consider an adaptive design
      in which two biomarkers are assessed. The trial is conducted in two stages. In
      the first stage, patients in the biomarker-guided arm are assessed using a
      standard and an alternative cheaper biomarker, with the standard biomarker
      guiding treatment. An analysis comparing biomarker results is then used to choose
      the biomarker to use for the remainder of the trial. The new biomarker is used if
      the results for the two biomarkers are sufficiently similar. RESULTS: We show
      that in practical situations the first-stage results can be used to adapt the
      trial without type I error rate inflation. We also show that there can be
      considerable cost gains with only a small loss in power in the case where the
      alternative biomarker is highly concordant with the standard one. CONCLUSIONS:
      Adaptive designs have an important role in reducing the cost and increasing the
      clinical utility of trials evaluating biomarker-guided treatment strategies.

PMID- 24667650
TI  - ERRbeta signalling through FST and BCAS2 inhibits cellular proliferation in
      breast cancer cells.
AB  - BACKGROUND: The overexpression of oestrogen-related receptor-beta (ERRbeta) in
      breast cancer patients is correlated with improved prognosis and longer relapse
      free survival, and the level of ERRbeta mRNA is inversely correlated with the S
      phase fraction of cells from breast cancer patients. METHODS: Chromatin
      immunoprecipitation (ChIP) cloning of ERRbeta transcriptional targets and gel
      supershift assays identified breast cancer amplified sequence 2 (BCAS2) and
      Follistatin (FST) as two important downstream genes that help to regulate
      tumourigenesis. Confocal microscopy, co-immunoprecipitation (CoIP), western
      blotting and quantitative real-time PCR confirmed the involvement of ERRbeta in
      oestrogen signalling. RESULTS: Overexpressed ERRbeta induced FST-mediated
      apoptosis in breast cancer cells, and E-cadherin expression was also enhanced
      through upregulation of FST. However, this anti-proliferative signalling function
      was challenged by ERRbeta-mediated BCAS2 upregulation, which inhibited FST
      transcription through the downregulation of beta-catenin/TCF4 recruitment to the
      FST promoter. Interestingly, ERRbeta-mediated upregulation of BCAS2 downregulated
      the major G1-S transition marker cyclin D1, despite the predictable oncogenic
      properties of BCAS2. INTERPRETATION: Our study provides the first evidence that
      ERRbeta, which is a coregulator of ERalpha also acts as a potential tumour
      suppressor molecule in breast cancer. Our current report also provides novel
      insights into the entire cascade of ERRbeta signalling events, which may lead to
      BCAS2-mediated blockage of the G1/S transition and inhibition of the epithelial
      to mesenchymal transition through FST-mediated regulation of E-cadherin.
      Importantly, matrix metalloprotease 7, which is a classical mediator of
      metastasis and E-cadherin cleavage, was also restricted as a result of ERRbeta
      mediated FST overexpression.

PMID- 24667652
TI  - Survival, growth and toxicity of Microcystis aeruginosa PCC 7806 in experimental
      conditions mimicking some features of the human gastro-intestinal environment.
AB  - Cyanotoxins (CTX) are widely produced by several cyanobacteria (CB), increasingly
      spreading in most water bodies and terrestrial habitats, and represent a risk for
      human health. CB are prokaryotes, and although mostly autotrophic, several
      examples of heterotrophy in symbiotic relationship with different organisms have
      been described. In addition to the known routes of exposure, it has been
      hypothesized that CB might 'colonize' human intestine with relevant implications
      for human health. Colonization is a complex process and requires specific
      features of the possible invaders. Still, a short-term persistence as living and
      toxin-producing organisms within the intestinal lumen of the host could represent
      an 'internal' source of exposure to CTX. In this work we ran microcosm
      experiments (4-18days), looking at Microcystis aeruginosa PCC7806 resistance and
      cyanotoxin-producing capabilities in darkness, 37 degrees C, pH 2, and subsequent
      recovery in a rich medium, in darkness, 37 degrees C, in the presence of enteric
      bacteria, mimicking few important features of the gastrointestinal environment.
      We measured cyanobacterial populations and growth, microcystin (MC) production
      and the presence of mcyB gene. M. aeruginosa could grow in the dark at 37 degrees
      C up to 17days, and survive at pH 2 at a rate between 30% and 70%, depending on
      the age and toxicity of the starting culture. Cell lysis resulted in a
      substantial amounts of MC released, not degraded at gastric pH. Following the
      acidic passage, still in the dark at 37 degrees C, M. aeruginosa restarted to
      grow within 24h for the next 3-4days, independently on the presence of intestinal
      bacteria, maintaining the MC cell quota and mcyB gene. Our results show new
      features of CB: a significant resistance of M. aeruginosa in conditions far from
      its optimal one, that is an environment mimicking some of the important
      characteristics of human gastrointestinal tract, suggesting the possibility of an
      internal source of exposure to CTX, with implications for the risk assessment. 

PMID- 24667653
TI  - Characterization of the structural determinants required for potent mechanism
      based inhibition of human cytochrome P450 1A1 by cannabidiol.
AB  - We previously demonstrated that cannabidiol (CBD) was a potent mechanism-based
      inhibitor of human cytochrome P450 1A1 (CYP1A1). However, the moiety of CBD that
      contributes to the potent mechanism-based inhibition of human CYP1A1 remains
      unknown. Thus, the effects of compounds structurally related to CBD on CYP1A1
      activity were examined with recombinant human CYP1A1 in order to characterize the
      structural requirements for potent inactivation by CBD. When preincubated in the
      presence of NADPH for 20min, olivetol, which corresponds to the pentylresorcinol
      moiety of CBD, enhanced the inhibition of the 7-ethoxyresorufin O-deethylase
      activity of CYP1A1. In contrast, d-limonene, which corresponds to the terpene
      moiety of CBD, failed to inhibit CYP1A1 activity in a metabolism-dependent
      manner. Pentylbenzene, which lacks two free phenolic hydroxyl groups, also did
      not enhance CYP1A1 inhibition. On the other hand, preincubation of the CBD-2'
      monomethyl ether (CBDM) and CBD-2',6'-dimethyl ether (CBDD) enhanced the
      inhibition of CYP1A1 activity. Inhibition by cannabidivarin (CBDV), which
      possessed a propyl side chain, was strongly potentiated by its preincubation.
      Orcinol, which has a methyl group, augmented CYP1A1 inhibition, whereas its
      derivative without an alkyl side chain, resorcinol, did not exhibit any
      metabolism-dependent inhibition. The preincubation of CBD-hydroxyquinone did not
      markedly enhance CYP1A1 inhibition. We further confirmed that olivetol, CBDM,
      CBDD, CBDV, and orcinol, as well as CBD (kinact=0.215min(-1)), inactivated CYP1A1
      activity; their kinact values were 0.154, 0.0638, 0.0643, 0.226, and 0.0353min(
      1), respectively. These results suggest that the methylresorcinol structure in
      CBD may have structurally important roles in the inactivation of CYP1A1. 

PMID- 24667654
TI  - Technology-related distracted walking behaviours in Manhattan's most dangerous
      intersections.
AB  - Use of mobile devices has been cited as a distraction while driving, and more
      recently, among pedestrians crossing urban streets. In 2010, over half of New
      York City traffic fatalities were pedestrians. The aim of this study was to
      estimate the prevalence of distracted walking due to pedestrians' use of
      headphones, mobile phones, or both. Data were gathered by direct observations at
      the 10 intersections in Manhattan with the highest frequency of pedestrian-motor
      vehicle collisions. More than 1 in 4 of the >3500 pedestrians observed were
      distracted by mobile electronic devices while crossing during the 'walk' (28.8%)
      and 'don't walk' (26.3%) signals. Poisson regression analyses established there
      was a significant difference in individuals talking on a mobile device during the
      'walk' signal versus the 'don't walk' signal; however, no other significant
      differences in other distracted walking behaviours were observed. This study
      contributes to the emerging literature on distracted walking behaviour by
      pedestrians in busy urban areas and can help to inform pedestrian-focused safety
      efforts. 

PMID- 24667655
TI  - Conservative DNA replication.

PMID- 24667656
TI  - STK31 is a cell-cycle regulated protein that contributes to the tumorigenicity of
      epithelial cancer cells.
AB  - Serine/threonine kinase 31 (STK31) is one of the novel cancer/testis antigens for
      which its biological functions remain largely unclear. Here, we demonstrate that
      STK31 is overexpressed in many human colorectal cancer cell lines and tissues.
      STK31 co-localizes with pericentrin in the centrosomal region throughout all
      phases of the cell cycle. Interestingly, when cells undergo mitosis, STK31 also
      localizes to the centromeres, central spindle, and midbody. This localization
      behavior is similar to that of chromosomal passenger proteins, which are known to
      be the important players of the spindle assembly checkpoint. The expression of
      STK31 is cell cycle-dependent through the regulation of a putative D-box near its
      C-terminal region. Ectopically-expressed STK31-GFP increases cell migration and
      invasive ability without altering the proliferation rate of cancer cells, whereas
      the knockdown expression of endogenous STK31 by lentivirus-derived shRNA results
      in microtubule assembly defects that prolong the duration of mitosis and lead to
      apoptosis. Taken together, our results suggest that the aberrant expression of
      STK31 contributes to tumorigenicity in somatic cancer cells. STK31 might
      therefore act as a potential therapeutic target in human somatic cancers. 

PMID- 24667657
TI  - Transient and permanent experience with fatty acids changes Drosophila
      melanogaster preference and fitness.
AB  - Food and host-preference relies on genetic adaptation and sensory experience. In
      vertebrates, experience with food-related cues during early development can
      change adult preference. This is also true in holometabolous insects, which
      undergo a drastic nervous system remodelling during their complete metamorphosis,
      but remains uncertain in Drosophila melanogaster. We have conditioned D.
      melanogaster with oleic (C18:1) and stearic (C18:0) acids, two common dietary
      fatty acids, respectively preferred by larvae and adult. Wild-type individuals
      exposed either during a transient period of development-from embryo to adult-or
      more permanently-during one to ten generation cycles-were affected by such
      conditioning. In particular, the oviposition preference of females exposed to
      each fatty acid during larval development was affected without cross-effect
      indicating the specificity of each substance. Permanent exposure to each fatty
      acid also drastically changed oviposition preference as well as major fitness
      traits (development duration, sex-ratio, fecundity, adult lethality). This
      suggests that D. melanogaster ability to adapt to new food sources is determined
      by its genetic and sensory plasticity both of which may explain the success of
      this generalist-diet species.

PMID- 24667658
TI  - Ultra-processed food products and obesity in Brazilian households (2008-2009).
AB  - BACKGROUND: Production and consumption of industrially processed food and drink
      products have risen in parallel with the global increase in overweight and
      obesity and related chronic non-communicable diseases. The objective of this
      study was to analyze the relationship between household availability of processed
      and ultra-processed products and the prevalence of excess weight (overweight plus
      obesity) and obesity in Brazil. METHODS: The study was based on data from the
      2008-2009 Household Budget Survey involving a probabilistic sample of 55,970
      Brazilian households. The units of study were household aggregates (strata),
      geographically and socioeconomically homogeneous. Multiple linear regression
      models were used to assess the relationship between the availability of processed
      and ultra-processed products and the average of Body Mass Index (BMI) and the
      percentage of individuals with excess weight and obesity in the strata,
      controlling for potential confounders (socio-demographic characteristics,
      percentage of expenditure on eating out of home, and dietary energy other than
      that provided by processed and ultra-processed products). Predictive values for
      prevalence of excess weight and obesity were estimated according to quartiles of
      the household availability of dietary energy from processed and ultra-processed
      products. RESULTS: The mean contribution of processed and ultra-processed
      products to total dietary energy availability ranged from 15.4% (lower quartile)
      to 39.4% (upper quartile). Adjusted linear regression coefficients indicated that
      household availability of ultra-processed products was positively associated with
      both the average BMI and the prevalence of excess weight and obesity, whereas
      processed products were not associated with these outcomes. In addition, people
      in the upper quartile of household consumption of ultra-processed products,
      compared with those in the lower quartile, were 37% more likely to be obese.
      CONCLUSION: Greater household availability of ultra-processed food products in
      Brazil is positively and independently associated with higher prevalence of
      excess weight and obesity in all age groups in this cross-sectional study.

PMID- 24667659
TI  - Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas.
AB  - Therapeutic options for patients with advanced pretreated soft tissue sarcomas
      are limited. However, in this setting, sorafenib has shown promising results. We
      reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib
      within a named patient program in Austria. Twelve physicians from eight different
      hospitals provided records for the analysis of data. Among the 33 patients, the
      predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other
      subtypes were represented by only one or two cases. Fifteen patients presented
      with metastases at the time of diagnosis. Another 17 patients developed
      metastases later in the course of the disease (data on one patient are missing).
      Most of the 33 patients had undergone resection of the primary (n=29, 88%) and
      half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for
      metastatic disease had been administered to 30 patients (91%). The majority had
      received two or more regimens of chemotherapy (n=25, 76%) before sorafenib
      treatment. The use of sorafenib resulted in a median time to treatment failure of
      92 days in patients with leiomyosarcoma and 45 days in patients with other
      histological subtypes. One-third of the patients derived benefits from treatment:
      four patients were documented with partial response and six with stabilized
      disease. In terms of treatment-related toxicity, skin problems of various degrees
      and gastrointestinal disturbances were frequently reported. In this retrospective
      analysis of heavily pretreated patients with advanced soft tissue sarcomas,
      sorafenib was associated with some antitumor activity and an acceptable toxicity
      profile. 

PMID- 24667660
TI  - LC-based targeted metabolomics analysis of nucleotides and identification of
      biomarkers associated with chemotherapeutic drugs in cultured cell models.
AB  - Treatment of mammalian cells with chemotherapeutic drugs can result in
      perturbations of nucleotide pools. Monitoring these perturbations in cultured
      tumor cells from human sources is useful for assessment of the effect of drug
      therapy and a better understanding of the mechanism of action of these drugs. In
      this study, three classes of chemotherapeutic drugs with different mechanisms of
      action were used in the development of drug-treated cell models. The LC-based
      targeted metabolomics analysis of nucleotides in cells of the control group and
      the drug-treated group was carried out. Several data processing methods were
      combined for the identification of potential biomarkers associated with the
      action of drugs, including one-way analysis of variance, principal component
      analysis, and receiver operating characteristic curves. Intriguingly, tumor cells
      of both the control group and the drug-treated groups can be distinguished from
      each other, and several variables were recognized as potential biomarkers, such
      as ATP, GMP, and UDP for antimetabolite agents, ATP, GMP, and CTP for DNA
      damaging agents, as well as GMP, ATP, UDP, and GDP for the mitotic spindle
      agents. Further validation of the potential biomarkers was performed using the
      receiver operating characteristic curve. Considering their corresponding area
      under the curve, which was larger than 0.9, it can be concluded that GMP and ATP
      are the best potential biomarkers for DNA-damaging drugs, as well as GMP, ATP,
      and UDP for the other two classes of drugs. This limited nucleotide approach
      cannot completely distinguish the mechanisms of the nine drugs, but it provides
      preliminary evidence for the role of pharmacometabolomics in the preclinical
      development of drugs at least. 

PMID- 24667661
TI  - Depletion of white adipose tissue in cancer cachexia syndrome is associated with
      inflammatory signaling and disrupted circadian regulation.
AB  - Involuntary weight loss in patients with cancer is the hallmark of cancer
      cachexia. The etiology of cachexia is multifactorial involving loss of skeletal
      muscle and adipose tissue associated with high systemic levels of acute phase
      proteins and inflammatory cytokines. While muscle wasting overtly impacts on
      cancer patient quality of life, loss of lipid depots represents a sustained
      energy imbalance. In this study fat depletion was examined in Colon-26 model of
      cancer cachexia, which is a widely used rodent model of this syndrome. We
      investigated diurnal expression of circadian rhythm regulators as well as key
      mediators of energy metabolism and cytokine signaling. Mice bearing the C26
      tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5
      fold increase in plasma levels of free fatty acids. These changes were associated
      with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated
      STAT3 and high SOCS3 gene expression levels. In addition perturbations in
      circadian regulation of lipid metabolism were also observed. Lipid catabolism did
      not appear to be influenced by the classical PKA pathway activating the lipase
      HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold
      increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was
      observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR
      pathways. This study provides evidence for activation of cytokine signaling and
      concomitant alterations in circadian rhythm and regulators of lipid metabolism in
      WAT of cachectic animals.

PMID- 24667662
TI  - Efficacy of two versus three-day regimens of dihydroartemisinin-piperaquine for
      uncomplicated malaria in military personnel in northern Cambodia: an open-label
      randomized trial.
AB  - INTRODUCTION: Emerging antimalarial drug resistance in mobile populations remains
      a significant public health concern. We compared two regimens of
      dihydroartemisinin-piperaquine in military and civilians on the Thai-Cambodian
      border to evaluate national treatment policy. METHODS: Efficacy and safety of two
      and three-day regimens of dihydroartemisinin-piperaquine were compared as a
      nested open-label evaluation within a malaria cohort study in 222 otherwise
      healthy volunteers (18% malaria-infected at baseline). The first 80 volunteers
      with slide-confirmed Plasmodium falciparum or vivax malaria were randomized 1:1
      to receive either regimen (total dose 360 mg dihydroartemisinin and 2880 mg
      piperaquine) and followed weekly for up to 6 months. The primary endpoint was
      malaria recurrence by day 42. Volunteers with vivax infection received primaquine
      at study discharge with six months follow-up. RESULTS: Eighty patients (60 vivax,
      15 falciparum, and 5 mixed) were randomized to dihydroartemisinin-piperaquine.
      Intention-to-treat all-species efficacy at Day 42 was 85% for the two-day regimen
      (95% CI 69-94) and 90% for the three-day regimen (95% CI 75-97). PCR-adjusted
      falciparum efficacy was 75% in both groups with nearly half (45%) still
      parasitemic at Day 3. Plasma piperaquine levels were comparable to prior
      published reports, but on the day of recrudescence were below measurable in vitro
      piperaquine IC50 levels in all falciparum treatment failures. CONCLUSIONS: In the
      brief period since introduction of dihydroartemisinin-piperaquine, there is early
      evidence suggesting declining efficacy relative to previous reports. Parasite
      IC50 levels in excess of plasma piperaquine levels seen only in treatment
      failures raises concern for clinically significant piperaquine resistance in
      Cambodia. These findings warrant improved monitoring of clinical outcomes and
      follow-up, given few available alternative drugs. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01280162.

PMID- 24667664
TI  - Intensive nursing care by an electronic followup system to promote secondary
      prevention after percutaneous coronary intervention: a randomized trial.
AB  - PURPOSE: To investigate the effectiveness of an intensive nursing care electronic
      followup system for cardiovascular risk management after percutaneous coronary
      intervention (PCI). METHODS: In total, 840 subjects who underwent PCI in a single
      hospital in Beijing between January 2010 and January 2012 were enrolled. All
      subjects were randomized into the control and intensive nursing care groups (n =
      420 each group). Both groups received standard secondary prevention according to
      guidelines. The control group received regular followup while the intensive
      nursing care group was closely monitored and followed by specific nursing staff
      with the electronic followup system. RESULTS: In total, 807 subjects were
      followed up for 1 year. Compared with subjects in the control group, those in the
      intensive group had decreased levels of total cholesterol (3.99 +/- 1.08 vs 3.76
      +/- 0.98; P < .05), systolic blood pressure (142.41 +/- 11.53 vs 135.71 +/- 14.57
      mm Hg; P < .05), low-density lipoprotein cholesterol (LDL-C) (2.72 +/- 1.01 vs
      2.42 +/- 0.81; P < .05), and body mass index (25.13 +/- 5.12 vs 24.23 +/- 6.22; P
      < .05); a higher percentage with target LDL-C < 2.6 mmol/L (66.99% vs 47.88%; P <
      .05); increased use of medication including aspirin (96.51% vs 99.26%; P < .05),
      clopidogrel (87.53% vs 98.77%; P < .05), statins (52.62% vs 93.10%; P < .05),
      beta-blockers (48.63% vs 61.33%; P < .05), and angiotensin-converting enzyme
      inhibitors (32.92% vs 61.82%; P < .05); and better dietary control and physical
      exercise (55.66% vs 26.18%, P < .05; 62.56% vs 38.65%, P < .05). CONCLUSIONS:
      Intensive nursing care by the electronic followup system may lead to an
      improvement in quality of secondary prevention after PCI, including risk factor
      control, the use of medication, and self-management abilities.

PMID- 24667665
TI  - Upper limb exercise prescription following cardiac surgery via median sternotomy:
      a web survey.
AB  - PURPOSE: Following cardiac surgery via median sternotomy, patients are routinely
      advised to adhere to upper limb restrictions to prevent the development of
      sternal complications. However, there is no definitive evidence to support the
      clinical application of such restrictions. The purpose of this study was to
      investigate current physiotherapy practice regarding upper limb exercise
      guidelines for this population, within outpatient cardiac rehabilitation in
      Australia. METHODS: Physiotherapists working within outpatient cardiac
      rehabilitation programs in Australia were invited to complete a Web survey.
      RESULTS: The response rate was 77%. The majority of respondents (96%) prescribed
      upper limb exercises to patients following median sternotomy, with 95% placing
      restrictions on these exercises. At 6 weeks postoperatively, 58% and 73% of
      respondents still placed restrictions on unloaded and loaded unilateral upper
      limb elevation exercises respectively; similarly, 55% and 74% placed restrictions
      on unloaded and loaded bilateral upper limb elevation exercises, respectively.
      However, there was a lack of consensus on the type and timing of these
      restrictions, with patient-reported pain being the main parameter used to guide
      upper limb exercise prescription and progression. Only 43% reported screening for
      sternal instability, and if detected, the majority based their management on
      clinical experience. CONCLUSIONS: There is significant variation in practice with
      respect to the prescription and progression of upper limb exercises, within
      outpatient cardiac rehabilitation in Australia. Further research is warranted to
      establish evidence-based guidelines for the upper limb rehabilitation of patients
      following cardiac surgery via median sternotomy.

PMID- 24667663
TI  - Dual effect of a polymorphism in the macrophage migration inhibitory factor gene
      is associated with new-onset Graves disease in a Taiwanese Chinese population.
AB  - Graves disease (GD) is an autoimmune disease. Macrophage migration inhibitory
      factor (MIF) is a potent cytokine that plays an important role in the regulation
      of immune responses. Two polymorphisms in the promoter region of MIF, rs5844572
      and rs755622, are known to affect MIF expression. The purpose of this study was
      to investigate the relationship between polymorphisms in the MIF gene promoter
      and the severity of GD. A total of 677 individuals, including 481 GD patients and
      196 ethnically matched healthy controls, were genotyped to identify differences
      in the distribution of the MIF polymorphisms rs5844572 and rs755622. Although
      there were no significant differences in the allele or genotype distributions
      among patients with different grades of goiter in GD and healthy controls, the
      distribution of the C allele, especially C/C genotype, of the rs755622 single
      nucleotide polymorphism (SNP) in MIF, may be as a risk factor for goiter
      initiation whereas a protector against development of severe goiter in patients
      with untreated GD (p<0.05). A goiter-developmental model incorporating genetic
      (MIF SNP rs755622) and environmental risk factors (gender, radioiodine treatment,
      thyroid gland surgery and vitiligo) significantly increased the prediction
      accuracy. Further studies are required to address the role of MIF polymorphisms,
      as well as their association with other candidate genes, in GD. 

PMID- 24667666
TI  - Shocktivity: ability and avoidance of daily activity behaviors in ICD patients.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) shocks terminate
      potentially life-threatening arrhythmias and may alter patient behavior. Patients
      are aware of which activities they have the ability to perform, but they may
      choose to avoid these behaviors after receiving a shock. This study examined ICD
      patient ability and avoidance of progressively exertive behaviors. METHODS: ICD
      patients (N = 443) across the United States were surveyed using an online measure
      including the 12-item Duke Activity Status Index. RESULTS: As expected, many
      patients reported being unable to participate in more physically exertive
      activities such as strenuous athletic exertion (68.8%), sex (35.4%), and running
      a short distance (49.0%). Avoidance rates were also relatively high, as patients
      who reported being able to participate in these activities also reported avoiding
      them (ie, strenuous athletics, 76.1%). Similarly, the majority of patients
      reported ability to engage in sexual activity (64.6%) but many chose to avoid
      sexual activity (51.0%). Multiple reasons were reported for avoidance, including
      fear of shock, fear of heart rate increase, doctor instruction, no desire, and an
      "other" option. CONCLUSION: Many ICD patients experience behavioral limitations
      because of both a perceived inability and preference to avoid exertive
      activities, and possibly a prescription to do so, particularly strenuous athletic
      exertion. Clinical and research attention to ICD patient activity levels and
      reasons for avoidance may improve daily functioning and help patients return to
      preimplant levels of activity.

PMID- 24667667
TI  - An expanding knowledge of the mechanisms and effects of alcohol consumption on
      cardiovascular disease.
AB  - Over the last 2 decades, observational evidence largely supports an association
      between light to moderate alcohol consumption (up to 1 drink per day in women and
      up to 2 drinks per day in men) and a lower risk of cardiovascular disease (CVD),
      largely driven by a reduction in coronary heart disease. Most studies suggest a
      nadir in risk in the light to moderate range of alcohol intake, which is then
      countered by an increase in cardiomyopathy, sudden death, and hemorrhagic stroke
      at higher drinking levels that offsets potential benefits. The mechanisms of
      cardioprotective effects of alcohol are complex and there are multiple pathways
      by which moderate alcohol consumption reduces the risk of CVD. Recent evidence
      continues to emerge on the physiologic and genetic mechanisms through which
      alcohol may reduce the risk of developing CVD. Ongoing debate also lingers
      whether there are important differences in cardiovascular effects according to
      alcoholic beverage type (beer vs red wine vs liquor). Another emerging area of
      interest is the role of alcohol consumption on the development of intermediate
      cardiovascular endpoints such as hypertension and diabetes that lead to the
      development of CVD as well as other important cardiovascular sequelae. Alcohol
      consumption has also been shown to impact the risk of other CVD endpoints
      including congestive heart failure, alcoholic cardiomyopathy, atrial
      fibrillation, and peripheral artery disease. Overall, alcohol still carries
      significant public health implications given its plausible benefits on CVD along
      with its well-documented adverse effects, warranting continued caution and a
      discussion with one's primary care provider regarding intake. 

PMID- 24667668
TI  - Diagnostic performance of skinfold method to identify obesity as measured by air
      displacement plethysmography in cardiac rehabilitation.
AB  - PURPOSE: To assess the diagnostic performance of the skinfold (SKF) method to
      detect obesity in patients enrolled in an outpatient cardiac rehabilitation (CR)
      program. METHODS: This study involves outpatients attending a phase II CR program
      who underwent air displacement plethysmography (ADP) to assess body composition.
      We measured body fat percentage (BF%), using a 3-site SKF method calculated
      through the Jackson-Pollock equation utilizing a Harpenden caliper. Air
      displacement plethysmography calculated BF% using a bicompartmental model,
      deriving the body composition after the direct calculation of body density (BD),
      using the Siri equation [(BF% = 495/BD) - 450]. We calculated the diagnostic
      performance of SKF to detect obesity, utilizing a BF% cutoff of >=35% for women
      and >=25% for men determined by SKF and ADP to define obesity. RESULTS: Our
      sample (n = 310) was 80% men, 60.2 +/- 11 years of age, had a mean weight of
      89.88 +/- 17.96 kg, height 173.38 +/- 8.68 cm, body mass index (BMI) 29.78 +/-
      5.01 kg/m, waist circumference 100.55 +/- 14.38 cm, and waist-to-hip ratio of
      0.96 +/- 0.09. The evaluation of the diagnostic performance of SKF to detect
      obesity showed a sensitivity of 57%, specificity of 93%, a positive predictive
      value of 97%, and a negative predictive value of 33%. These values were not
      different from the diagnostic performance of BMI to detect obesity as defined by
      BF%. SKF and BMI misclassified 43% and 49% of obese patients as nonobese,
      respectively. CONCLUSION: Our findings underscore the limitation of using SKF to
      assess body fatness in the CR setting.

PMID- 24667669
TI  - Cutaneous papillary squamous cell carcinoma.

PMID- 24667670
TI  - Avian influenza A virus infection in humans.

PMID- 24667672
TI  - Human tibial torsion--morphometric assessment and clinical relevance.
AB  - BACKGROUND: Tibial torsion is an important anatomical parameter in clinical
      practice and displays variability among individuals. These variations are
      extremely significant in view of alignment guides such as those related to
      rotational landmarks of tibia in total knee arthroplasty. Further, precise
      knowledge and information pertaining to angle of tibial torsion also helps in
      correction of traumatic malunion or congenital maltorsion of tibia. METHODS: The
      present study was carried out to determine the angle of tibial torsion in 100
      adult dry tibia bones in the Department of Anatomy, Government Medical College,
      Amritsar. The study group comprised 50 males and 50 females with equal number of
      right- and left-sided bones. The measurements were meticulously recorded and the
      data were subjected to statistical analysis. The results were analyzed and
      discussed in the light of existing literature. RESULTS: On the right side, it was
      found to be 29.84 degrees  +/- 4.86 degrees  degrees  (range = 22.00 degrees  
      38.00 degrees ) in males and 28.92 degrees  +/- 5.10 degrees  degrees  (range =
      15.00 degrees -38.00 degrees ) in females. On the left side, it was found to be
      28.00 degrees  +/- 4.94 degrees  degrees  (range = 20.00 degrees -40.00 degrees 
      degrees ) in males and 28.12 degrees  +/- 4.28 degrees  degrees  (range = 20.00
      degrees -37.00 degrees  degrees ) in females. CONCLUSION: The present study is an
      endeavor to provide baseline data with reference to the angle of tibial torsion
      in the Indian population. The results of the study assume special importance in
      view of the technical advancements in reconstructive surgical procedures in
      orthopedic practice.

PMID- 24667673
TI  - In vivo morphometry of menisci of the knee in South Indians: a preliminary study.
AB  - BACKGROUND: Since the in vivo morphometric data on the menisci of the knee joint
      of Indian subjects are scarce, we hereby studied the width and thickness of the
      menisci using Magnetic Resonance Imaging (MRI) to establish standard dimensions
      of the normal medial and lateral meniscus as an aid to orthopaedic surgery.
      METHODS: Eighty menisci from 40 knee joints were analysed in each of three
      regions, the anterior horn, the mid body and the posterior horn. The thickness
      and width of the menisci were measured in sagittal and coronal T1-weighted and T2
      weighted MRI images and analysed statistically. RESULTS: The mean thickness of
      medial meniscus at the anterior horn, mid body, and posterior horn were 6.3 +/-
      1.1 mm, 5.2 +/- 1.3 mm, and 6.9 +/- 1.1 mm, respectively. The respective values
      for the lateral meniscus were 4.8 +/- 0.7 mm, 6.4 +/- 1.1 mm, and 7.0 +/- 0.9 mm.
      The mean width of medial meniscus at the anterior horn, mid body, and posterior
      horn were 10.5 +/- 1.2 mm, 7.8 +/- 1 mm and 13.9 +/- 0.9 mm, respectively. The
      widths of lateral meniscus at the same regions were 11.8 +/- 1.4 mm, 8.6 +/- 1.2
      mm, and 12.0 +/- 0.9 mm, respectively. The lateral meniscus was significantly
      wider than medial at the anterior horn and mid body (p = 0.00). In contrast, the
      posterior horn of medial meniscus was significantly wider than lateral meniscus.
      Both menisci were significantly wider at their posterior horn, followed by the
      anterior horn and were significantly narrower at their mid body. CONCLUSION: The
      present study provides new information on the meniscal thickness and width in
      South Indians that can be used in planning of orthopaedic and arthroscopic
      surgeries of the knee joint. However, the study needs to be analyzed with a large
      sample size for the better interpretation.

PMID- 24667671
TI  - The versatile functions of ATM kinase.
AB  - Ataxia-telangiectasia mutated (ATM) kinase, the mutation of which causes the
      autosomal recessive disease ataxia-telangiectasia, plays an essential role in the
      maintenance of genome stability. Extensive studies have revealed that activated
      ATM signals to a massive list of proteins to facilitate cell cycle checkpoints,
      DNA repair, and many other aspects of physiological responses in the event of DNA
      double-strand breaks. ATM also plays functional roles beyond the well
      characterized DNA damage response (DDR). In this review article, we discuss the
      recent findings on the molecular mechanisms of ATM in DDR, the mitotic spindle
      checkpoint, as well as hyperactive ATM signaling in cancer invasion and
      metastasis. 

PMID- 24667674
TI  - Surgical risks and perioperative complications of instrumented lumbar surgery in
      patients with liver cirrhosis.
AB  - BACKGROUND: Patients with liver cirrhosis have high surgical risks due to
      malnutrition, impaired immunity, coagulopathy, and encephalopathy. However, there
      is no information in English literature about the results of liver cirrhotic
      patients who underwent instrumented lumbar surgery. The purpose of this study is
      to report the perioperative complications, clinical outcomes and determine the
      surgical risk factors in cirrhotic patients. METHODS: We retrospectively reviewed
      29 patients with liver cirrhosis who underwent instrumented lumbar surgery
      between 1997 and 2009. The hepatic functional reserves of the patients were
      recorded according to the Child-Turcotte-Pugh scoring system. Besides, fourteen
      other variables and perioperative complications were also collected. To determine
      the risks, we divided the patients into two groups according to whether or not
      perioperative complications developed. RESULTS: Of the 29 patients, 22 (76%)
      belonged to Child class A and 7 (24%) belonged to Child class B. Twelve patients
      developed one or more complications. Patients with Child class B carried a
      significantly higher incidence of complications than those with Child class A (p
      = 0.011). In the Child class A group, patients with 6 points had a significantly
      higher incidence of complications than those with 5 points (p = 0.025). A low
      level of albumin was significantly associated with higher risk, and a similar
      trend was also noted for the presence of ascites although statistical difference
      was not reached. CONCLUSION: The study concludes that patients with liver
      cirrhosis who have undergone instrumented lumbar surgery carry a high risk of
      developing perioperative complications, especially in those with a Child-Turcotte
      Pugh score of 6 or more.

PMID- 24667675
TI  - The impact of climate factors on the prevalence of urolithiasis in Northern
      Taiwan.
AB  - BACKGROUND: Urolithiasis is a common disease with high prevalence and recurrence.
      Its incidence varies in different geographic locations, and there are evidences
      that meteorological factors also affect urinary stone formation. The aim of this
      study is to analyze the effects of climate parameters on the numbers of shockwave
      treatments for urinary stones in our hospital, in order to understand the effects
      of these parameters on the prevalence of urolithiasis in northern Taiwan.
      METHODS: We retrospectively reviewed the records of extracorporeal shockwave
      lithotripsy (ESWL) performed in our hospital from December 2006 to November 2011.
      Repeated ESWL performed in the same patient within 1 month was excluded, and we
      only counted as one ESWL in our study. Climate data of the corresponding months
      were collected from Central Weather Bureau. The available monthly meteorological
      data included highest, lowest, and average temperatures, humidity, rainfall,
      total rain days, sunshine hours, average atmospheric pressure, and wind speed.
      RESULTS: Monthly ESWL number was positively correlated to temperature (r =
      0.696), sunshine hours (r = 0.515), and wind speed (r = 0.369), while it was
      negatively correlated to humidity (r = -0.441) and atmospheric pressure (r = 
      0.568). Average monthly temperature had the strongest correlation to ESWL number
      (r2 = 0.484). Monthly rainfall and rain days were not significantly correlated to
      ESWL number. To investigate the climate parameters together, we introduced these
      correlated factors into the multivariate linear regression model which
      demonstrated only temperature (beta = 1.438, 95% CI: 3.703-9.144, p < 0.001) and
      atmospheric pressure (beta = 0.803, 95% CI: 0.790-5.428, p = 0.010) to be
      independently related to monthly ESWL number. CONCLUSION: Temperature and
      atmospheric pressure are associated with monthly ESWL number. Ambient temperature
      is the most important climate factor affecting the prevalence of urolithiasis in
      northern Taiwan.

PMID- 24667676
TI  - Fungal contaminants in cytopathology specimens.
AB  - A pseudo-epidemic of environmental fungi, most likely by Fusarium spp., leading
      to inappropriate investigations for disseminated systemic mycosis is described.
      Subtle diagnostic clues, including the specimens affected, the nature of the host
      response, and the type of fungal elements noted helped to determine the nature of
      contaminants. The potential pitfall can be avoided by the knowledge of pertinent
      disease biology, prompt consultation for infectious diseases, and investigations
      of the potential environmental sources followed by source control. 

PMID- 24667677
TI  - In vivo time-resolved microtomography reveals the mechanics of the blowfly flight
      motor.
AB  - Dipteran flies are amongst the smallest and most agile of flying animals. Their
      wings are driven indirectly by large power muscles, which cause cyclical
      deformations of the thorax that are amplified through the intricate wing hinge.
      Asymmetric flight manoeuvres are controlled by 13 pairs of steering muscles
      acting directly on the wing articulations. Collectively the steering muscles
      account for <3% of total flight muscle mass, raising the question of how they can
      modulate the vastly greater output of the power muscles during manoeuvres. Here
      we present the results of a synchrotron-based study performing micrometre
      resolution, time-resolved microtomography on the 145 Hz wingbeat of blowflies.
      These data represent the first four-dimensional visualizations of an organism's
      internal movements on sub-millisecond and micrometre scales. This technique
      allows us to visualize and measure the three-dimensional movements of five of the
      largest steering muscles, and to place these in the context of the deforming
      thoracic mechanism that the muscles actuate. Our visualizations show that the
      steering muscles operate through a diverse range of nonlinear mechanisms,
      revealing several unexpected features that could not have been identified using
      any other technique. The tendons of some steering muscles buckle on every
      wingbeat to accommodate high amplitude movements of the wing hinge. Other
      steering muscles absorb kinetic energy from an oscillating control linkage, which
      rotates at low wingbeat amplitude but translates at high wingbeat amplitude.
      Kinetic energy is distributed differently in these two modes of oscillation,
      which may play a role in asymmetric power management during flight control.
      Structural flexibility is known to be important to the aerodynamic efficiency of
      insect wings, and to the function of their indirect power muscles. We show that
      it is integral also to the operation of the steering muscles, and so to the
      functional flexibility of the insect flight motor. 

PMID- 24667678
TI  - Mediolateral episiotomy significantly reduces the risk of obstetric-associated
      anal sphincter injury (OASIS) in women who deliver via vacuum extraction.

PMID- 24667679
TI  - Arthroscopic partial meniscectomy provides no benefit over sham surgery in the
      setting of isolated degenerative medial meniscal tears without osteoarthritis.

PMID- 24667681
TI  - Improved FTA methodology and application to subsea pipeline reliability design.
AB  - An innovative logic tree, Failure Expansion Tree (FET), is proposed in this
      paper, which improves on traditional Fault Tree Analysis (FTA). It describes a
      different thinking approach for risk factor identification and reliability risk
      assessment. By providing a more comprehensive and objective methodology, the
      rather subjective nature of FTA node discovery is significantly reduced and the
      resulting mathematical calculations for quantitative analysis are greatly
      simplified. Applied to the Useful Life phase of a subsea pipeline engineering
      project, the approach provides a more structured analysis by constructing a tree
      following the laws of physics and geometry. Resulting improvements are summarized
      in comparison table form. 

PMID- 24667680
TI  - Seasonal variations and resilience of bacterial communities in a sewage polluted
      urban river.
AB  - The Zenne River in Brussels (Belgium) and effluents of the two wastewater
      treatment plants (WWTPs) of Brussels were chosen to assess the impact of
      disturbance on bacterial community composition (BCC) of an urban river. Organic
      matters, nutrients load and oxygen concentration fluctuated highly along the
      river and over time because of WWTPs discharge. Tag pyrosequencing of bacterial
      16S rRNA genes revealed the significant effect of seasonality on the richness,
      the bacterial diversity (Shannon index) and BCC. The major grouping: -winter/fall
      samples versus spring/summer samples- could be associated with fluctuations of in
      situ bacterial activities (dissolved and particulate organic carbon
      biodegradation associated with oxygen consumption and N transformation). BCC of
      the samples collected upstream from the WWTPs discharge were significantly
      different from BCC of downstream samples and WWTPs effluents, while no
      significant difference was found between BCC of WWTPs effluents and the
      downstream samples as revealed by ANOSIM. Analysis per season showed that
      allochthonous bacteria brought by WWTPs effluents triggered the changes in
      community composition, eventually followed by rapid post-disturbance return to
      the original composition as observed in April (resilience), whereas community
      composition remained altered after the perturbation by WWTPs effluents in the
      other seasons. 

PMID- 24667682
TI  - Biomanufacture of human platelets for transfusion: Rationale and approaches.
AB  - Platelets for transfusion obtained from volunteer blood donors are a limited
      resource. Given the increased range of donor restrictions to prevent transmission
      of disease and the decline in volunteer blood donors, there is a diminishing
      supply of blood for transfusion. Production of mature blood cells from
      hematopoietic stem cells via large-scale manufacture is an alternative way of
      meeting transfusion demands. In this review, we provide a detailed outline of the
      challenges and opportunities for the biomanufacture of platelets. We describe the
      scale required for platelet biomanufacture to deliver sufficient cells for
      transfusion, provide a brief outline of the current understanding of
      megakaryopoiesis and thrombogenesis, and highlight how the current understanding
      impacts the design of culture systems and bioreactors for producing platelets. 

PMID- 24667683
TI  - Statins inhibit ABCB1 and ABCG2 drug transporter activity in chronic myeloid
      leukemia cells and potentiate antileukemic effects of imatinib.
AB  - Despite undisputed success of tyrosine kinase inhibitors in the therapy of
      chronic myeloid leukemia (CML), development of drug resistance and inability to
      cure the disease challenge clinicians and researchers. Additionally, recent
      reports regarding cardiovascular toxicities of second and third generation
      tyrosine kinase inhibitors prove that there is still a place for novel
      therapeutic combinations in CML. We have previously shown that statins are able
      to modulate activity of chemotherapeutics or antibodies used in oncology.
      Therefore, we decided to verify that statins are able to potentiate antileukemic
      activity of imatinib, still a frontline treatment of CML. Lovastatin, a
      cholesterol lowering drug, synergistically potentiates antileukemic activity of
      imatinib in cell lines and in primary CD34+ CML cells from patients in different
      phases of the disease, including patients resistant to imatinib with no
      detectable mutations. This effect is related to increased intracellular
      concentration of imatinib in CD34+ CML cells and cell lines measured using uptake
      of (14)C-labeled imatinib. Lovastatin does not influence influx but significantly
      inhibits efflux of imatinib mediated by ATP-binding cassette (ABC) transporters:
      ABCB1 and ABCG2. The addition of cholesterol completely reverses these effects.
      Statins do not affect expression of ABCB1 and ABCG2 genes. The effects are drug
      class specific, as observed with other statins. Our results suggest that statins
      may offer a valuable addition to imatinib in a select group of CML patients. 

PMID- 24667684
TI  - Patterns of gene expression in peripheral blood mononuclear cells and outcomes
      from patients with sepsis secondary to community acquired pneumonia.
AB  - Mechanisms governing the inflammatory response during sepsis have been shown to
      be complex, involving cross-talk between diverse signaling pathways. Current
      knowledge regarding the mechanisms underlying sepsis provides an incomplete
      picture of the syndrome, justifying additional efforts to understand this
      condition. Microarray-based expression profiling is a powerful approach for the
      investigation of complex clinical conditions such as sepsis. In this study, we
      investigate whole-genome expression profiles in mononuclear cells from survivors
      (n = 5) and non-survivors (n = 5) of sepsis. To circumvent the heterogeneity of
      septic patients, only patients admitted with sepsis caused by community-acquired
      pneumonia were included. Blood samples were collected at the time of sepsis
      diagnosis and seven days later to evaluate the role of biological processes or
      genes possibly involved in patient recovery. Principal Components Analysis (PCA)
      profiling discriminated between patients with early sepsis and healthy
      individuals. Genes with differential expression were grouped according to Gene
      Ontology, and most genes related to immune defense were up-regulated in septic
      patients. Additionally, PCA in the early stage was able to distinguish survivors
      from non-survivors. Differences in oxidative phosphorylation seem to be
      associated with clinical outcome because significant differences in the
      expression profile of genes related to mitochondrial electron transport chain
      (ETC) I-V were observed between survivors and non-survivors at the time of
      patient enrollment. Global gene expression profiles after seven days of sepsis
      progression seem to reproduce, to a certain extent, patterns collected at the
      time of diagnosis. Gene expression profiles comparing admission and follow-up
      samples differed between survivors and non-survivors, with decreased expression
      of genes related to immune functions in non-survivors. In conclusion, genes
      related to host defense and inflammatory response ontology were up-regulated
      during sepsis, consistent with the need for a host response to infection, and the
      sustainability of their expression in follow-up samples was associated with
      outcomes.

PMID- 24667686
TI  - Haploidentical stem cell transplantation in DOCK8 deficiency - Successful control
      of pre-existing severe viremia with a TCRabeta/CD19-depleted graft and antiviral
      treatment.

PMID- 24667687
TI  - A new technique of first carpometacarpal joint suspension arthroplasty with
      palmaris longus tendon graft.
AB  - This article describes a novel technique of suspending the first metacarpal after
      trapeziectomy with a palmaris longus tendon graft in the specific situation of a
      patient with Eaton and Lambert stage IV thumb base osteoarthritis with proximal
      subluxation of the first metacarpal and ulnar translation of the carpus on the
      radius, such that without suspension the first metacarpal would articulate with
      the radial styloid after trapeziectomy. The advantage of the palmaris longus
      tendon graft as opposed to techniques using the flexor carpi radialis or abductor
      pollicis longus tendons is that this technique anchors the first metacarpal in a
      more distal position than the latter techniques allow. No complications were
      encountered and the patient remains pain-free at 6 months with improved pinch and
      grip strength and function.

PMID- 24667685
TI  - Using immunomic approach to enhance tumor-associated autoantibody detection in
      diagnosis of hepatocellular carcinoma.
AB  - To explore the possibility of using a mini-array of multiple tumor-associated
      antigens (TAAs) as an approach to the diagnosis of hepatocellular carcinoma
      (HCC), 14 TAAs were selected to examine autoantibodies in sera from patients with
      chronic hepatitis, liver cirrhosis and HCC by immunoassays. Antibody frequency to
      any individual TAA in HCC varied from 6.6% to 21.1%. With the successive addition
      of TAAs to the panel of TAAs, there was a stepwise increase of positive antibody
      reactions. The sensitivity and specificity of 14 TAAs for immunodiagnosis of HCC
      was 69.7% and 83.0%, respectively. This TAA mini-array also identified 43.8% of
      HCC patients who had normal alpha-fetoprotein (AFP) levels in serum. In summary,
      this study further supports the hypothesis that a customized TAA array used for
      detecting anti-TAA autoantibodies can constitute a promising and powerful tool
      for immunodiagnosis of HCC and may be especially useful in patients with normal
      AFP levels.

PMID- 24667688
TI  - OVA66 increases cell growth, invasion and survival via regulation of IGF-1R-MAPK
      signaling in human cancer cells.
AB  - Ovarian cancer-associated antigen 66 (OVA66), also known as CML66 (GenBank
      Accession No. AF283301), was first identified in an ovarian carcinoma
      complementary DNA (cDNA) expression library and was shown to play a role in
      tumorigenesis. Here, we find that OVA66 influences tumorigenesis by regulating
      the type I insulin-like growth factor receptor (IGF-1R) signaling pathway. Stable
      knockdown of OVA66 in cancer cells attenuated phosphorylation of IGF-1R and
      extracellular signal-regulated kinase 1/2 (ERK1/2)-Hsp27; similarly, a higher
      level of p-IGF-1R and ERK1/2-Hsp27 signaling was also detected after OVA66
      overexpression in HO8910 cells. In vivo knockdown of OVA66 both reduced tumor
      burden in nude mice and decreased phosphorylation of IGF-1R, ERK1/2 and hsp27. We
      blocked IGF-1R function both by small interfering RNA (siRNA) and with the
      chemical inhibitor Linsitinib (OSI-906). By either method, tumorigenesis was
      inhibited regardless of OVA66 expression; thus, mechanistically, IGF-1R,
      probably, lies downstream of OVA66 in cancer cells. We also found that OVA66
      regulates expression of murine double minute 2 (MDM2); this attenuates
      ubiquitination of IGF-1R in response to IGF-1 stimulation and promotes active
      ERK1/2 signaling. Thus, we propose that combined overexpression of OVA66 and MDM2
      promotes oncogenesis by enhancing activation of the IGF-1R-ERK1/2 signaling
      pathway. 

PMID- 24667689
TI  - Ocular pseudoexfoliation syndrome and vascular disease: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: Many studies have assessed the association between ocular
      pseudoexfoliation syndrome (PEX) and vascular disease and produced controversial
      results. We performed a meta-analysis of epidemiologic studies to evaluate this
      relationship. METHODS: Eligible studies that reported the incidence of vascular
      disease among PEX and control groups were identified via computer searches and
      reviewing the reference lists of the key articles. The summary odds ratio (OR)
      and 95% confidence interval (CI) were pooled using a random-effects model. Meta
      regression to assess heterogeneity by several covariates and a subgroup analysis
      on study design and population were performed. Publication bias was tested by
      Begg's funnel plot and Egger's regression test. RESULTS: Sixteen eligible studies
      involving 8,533 PEX patients and 135,720 control patients were included in the
      meta-analysis. All studies were performed primarily in whites with a mean age
      between 54.7 and 77.1 years. The overall combined ORs for patients with PEX
      compared with the reference group were 1.72 (95% CI: 1.31 to 2.26) for any
      vascular disease, 1.61 (95% CI: 1.22 to 2.14) for coronary heart disease, 1.59
      (95% CI: 1.12 to 2.23) for cerebrovascular disease, and 2.48 (95% CI: 1.30 to
      4.72) for aortic aneurysm. There was evidence of statistical heterogeneity;
      however, subgroup and sensitivity analyses showed this result to be robust. No
      evidence of publication bias was observed. CONCLUSIONS: The overall current
      literature suggests that PEX was associated with increased risk of vascular
      disease. Because of the limitations of the included studies and meta-analysis,
      the findings need to be confirmed in future research via well-designed cohort
      studies.

PMID- 24667690
TI  - Response to developmental-behavioral pediatrics-have we forged an identity?

PMID- 24667691
TI  - Adenovirus-mediated eNOS expression augments liver injury after
      ischemia/reperfusion in mice.
AB  - Hepatic ischemia/reperfusion (l/R) injury continues to be a critical problem. The
      role of nitric oxide in liver I/R injury is still controversial. This study
      examines the effect of endothelial nitric oxide synthase (eNOS) over-expression
      on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS) was
      administered by tail vein injection into C57BL/6 mice. Control mice received
      either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic
      ischemia was performed 3 days after adenovirus treatment, and mice were
      sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over
      expression caused increased liver injury as evidenced by elevated AST and ALT
      levels and decreased hepatic ATP content. While necrosis was not pervasive in any
      group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected
      livers. Western blotting demonstrated increased levels of protein nitration and
      upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that
      over-expression of eNOS is detrimental in the setting of hepatic I/R. 

PMID- 24667692
TI  - EEG-confirmed epileptic activity in a cat with VGKC-complex/LGI1 antibody
      associated limbic encephalitis.
AB  - A 5-year-old, female client-owned cat presented with acute onset of focal
      epileptic seizures with orofacial twitching and behavioural changes. Magnetic
      resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was
      consistent with ictal epileptic seizure activity. After antiepileptic and
      additional corticosteroid treatment, the cat recovered and by 10 months of follow
      up was seizure-free without any problem. Retrospectively, antibodies to LGI1, a
      component of the voltage-gated potassium channel-complex, were identified. Feline
      focal seizures with orofacial involvement have been increasingly recognised in
      client-owned cats, and autoimmune limbic encephalitis was recently suggested as a
      possible aetiology. This is the first report of EEG, MRI and long-term follow-up
      of this condition in cats which is similar to human limbic encephalitis. 

PMID- 24667693
TI  - Mechanical performance of a biocompatible biocide soda-lime glass-ceramic.
AB  - A biocompatible soda-lime glass-ceramic in the SiO2-Na2O-Al2O3-CaO-B2O3 system
      containing combeite and nepheline as crystalline phases, has been obtained at 750
      degrees C by two different routes: (i) pressureless sintering and (ii) Spark
      Plasma Sintering. The SPS glass-ceramic showed a bending strength, Weibull
      modulus, and toughness similar values to the cortical human bone. This material
      had a fatigue limit slightly superior to cortical bone and at least two times
      higher than commercial dental glass-ceramics and dentine. The in vitro studies
      indicate that soda-lime glass-ceramic is fully biocompatible. The in vivo studies
      in beagle jaws showed that implanted SPS rods presented no inflammatory changes
      in soft tissues surrounding implants in any of the 10 different cases after four
      months implantation. The radiological analysis indicates no signs of
      osseointegration lack around implants. Moreover, the biocide activity of SPS
      glass-ceramic versus Escherichia coli, was found to be >4log indicating that it
      prevents implant infections. Because of this, the SPS new glass-ceramic is
      particularly promising for dental applications (inlay, crowns, etc). 

PMID- 24667694
TI  - Biphasic role of chondroitin sulfate in cardiac differentiation of embryonic stem
      cells through inhibition of Wnt/beta-catenin signaling.
AB  - The glycosaminoglycan chondroitin sulfate is a critical component of
      proteoglycans on the cell surface and in the extracellular matrix. As such,
      chondroitin sulfate side chains and the sulfation balance of chondroitin play
      important roles in the control of signaling pathways, and have a functional
      importance in human disease. In contrast, very little is known about the roles of
      chondroitin sulfate molecules and sulfation patterns during mammalian development
      and cell lineage specification. Here, we report a novel biphasic role of
      chondroitin sulfate in the specification of the cardiac cell lineage during
      embryonic stem cell differentiation through modulation of Wnt/beta-catenin
      signaling. Lineage marker analysis demonstrates that enzymatic elimination of
      endogenous chondroitin sulfates leads to defects specifically in cardiac
      differentiation. This is accompanied by a reduction in the number of beating
      cardiac foci. Mechanistically, we show that endogenous chondroitin sulfate
      controls cardiac differentiation in a temporal biphasic manner through inhibition
      of the Wnt/beta-catenin pathway, a known regulatory pathway for the cardiac
      lineage. Treatment with a specific exogenous chondroitin sulfate, CS-E, could
      mimic these biphasic effects on cardiac differentiation and Wnt/beta-catenin
      signaling. These results establish chondroitin sulfate and its sulfation balance
      as important regulators of cardiac cell lineage decisions through control of the
      Wnt/beta-catenin pathway. Our work suggests that targeting the chondroitin
      biosynthesis and sulfation machinery is a novel promising avenue in regenerative
      strategies after heart injury. 

PMID- 24667695
TI  - Predicting mortality among hospitalized children with respiratory illness in
      Western Kenya, 2009-2012.
AB  - BACKGROUND: Pediatric respiratory disease is a major cause of morbidity and
      mortality in the developing world. We evaluated a modified respiratory index of
      severity in children (mRISC) scoring system as a standard tool to identify
      children at greater risk of death from respiratory illness in Kenya. MATERIALS
      AND METHODS: We analyzed data from children <5 years old who were hospitalized
      with respiratory illness at Siaya District Hospital from 2009-2012. We used a
      multivariable logistic regression model to identify patient characteristics
      predictive for in-hospital mortality. Model discrimination was evaluated using
      the concordance statistic. Using bootstrap samples, we re-estimated the
      coefficients and the optimism of the model. The mRISC score for each child was
      developed by adding up the points assigned to each factor associated with
      mortality based on the coefficients in the multivariable model. RESULTS: We
      analyzed data from 3,581 children hospitalized with respiratory illness;
      including 218 (6%) who died. Low weight-for-age [adjusted odds ratio (aOR) = 2.1;
      95% CI 1.3-3.2], very low weight-for-age (aOR = 3.8; 95% CI 2.7-5.4), caretaker
      reported history of unconsciousness (aOR = 2.3; 95% CI 1.6-3.4), inability to
      drink or breastfeed (aOR = 1.8; 95% CI 1.2-2.8), chest wall in-drawing (aOR =
      2.2; 95% CI 1.5-3.1), and being not fully conscious on physical exam (aOR = 8.0;
      95% CI 5.1-12.6) were independently associated with mortality. The positive
      predictive value for mortality increased with increasing mRISC scores.
      CONCLUSIONS: A modified RISC scoring system based on a set of easily measurable
      clinical features at admission was able to identify children at greater risk of
      death from respiratory illness in Kenya.

PMID- 24667696
TI  - Confined placental origin of the circulating cell free fetal DNA revealed by a
      discordant non-invasive prenatal test result in a trisomy 18 pregnancy.
AB  - BACKGROUND: Non-invasive prenatal testing (NIPT) by massively parallel sequencing
      is a useful clinical test for the detection of common fetal aneuploidies. While
      the accuracy of aneuploidy detection can approach 100%, results discordant with
      the fetus are occasionally reported. In this study we investigated the basis of a
      discordant T21 positive and T18 negative NIPT result associated with a T18 fetus
      confirmed by karyotyping. METHODS: Massively parallel sequencing was used to
      detect fetal DNA in maternal circulating plasma. The parental origin and nature
      of the fetal and placental aneuploidies were investigated by quantitative
      fluorescent PCR of short tandem repeat (STR) sequences and by copy number
      variation (CNV) sequencing. RESULTS: There was no evidence of T21 maternal
      mosaicism, T21 microchimerism or a vanishing twin to explain the discordant NIPT
      result. However, examination of multiple placental biopsies showed both T21 and
      T18 mosaicism, including one confined region with a significantly higher
      proportion of T21 cells. Based on fetal DNA fractions and average mosaicism
      levels, the effective T21 and T18 fetal DNA fractions should have been sufficient
      for the detection of both trisomies. CONCLUSIONS: In this pregnancy, we speculate
      that confined placental region(s) with higher proportions of T21 cells were
      preferentially releasing fetal DNAs into the maternal circulation. This study
      highlights placental mosaicism as a significant risk factor for discordant NIPT
      results.

PMID- 24667697
TI  - The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver
      disease in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The serum cytokeratin-18 fragment (CK-18) concentration has been
      suggested to be a biomarker of nonalcoholic fatty liver disease (NAFLD), although
      its usefulness in patients with type 2 diabetes mellitus (T2DM) is unknown.
      METHODS: The study was divided into two parts. In the first cross-sectional
      study, a total of 200 patients with T2DM and 58 healthy control subjects were
      recruited. NAFLD was diagnosed using ultrasonography. In the subsequent
      longitudinal study, we evaluated the three-month change (Delta) in the CK-18
      concentration and other parameters in 40 T2DM patients with NAFLD. RESULTS: The
      serum CK-18 values were significantly higher in the NAFLD group than in the
      nonNAFLD group among both diabetic and nondiabetic subjects. The CK-18
      concentration was found to be an independent determinant of NAFLD and was
      positively correlated with the ultrasonography score and AST and ALT
      concentrations in the T2DM patients. Positive correlations were also identified
      between the CK-18 and transaminase concentrations in the T2DM and NAFLD cohorts.
      DeltaCK-18 was found to be significantly associated with DeltaBMI in the T2DM
      patients with NAFLD. CONCLUSIONS: A dose effect between the CK-18 concentration
      and the severity of NAFLD was found in the T2DM patients; thus, the CK-18
      concentration is a potentially useful biomarker for assessing the efficacy of
      treatment and the improvement in NAFLD in patients with T2DM.

PMID- 24667698
TI  - Novel frame-shift mutations of GLI3 gene in non-syndromic postaxial polydactyly
      patients.
AB  - Polydactyly is a common congenital limb deformity. This anomaly may occur in
      isolation (non-syndromic) or as part of a syndrome. The glioma-associated
      oncogene family zinc finger 3 (GLI3) is known to be associated with both
      syndromic and non-syndromic polydactyly. GLI3 plays a predominant role in the
      pathogenesis of syndromic polydactyly: mutations have been identified in 68% of
      patients with Greig cephalopolysyndactyly syndrome and 91% of patients with
      Pallister-Hall syndrome. The knowledge regarding the contribution of GLI3 in non
      syndromic polydactyly is currently very limited. In this study, we assembled a
      cohort of individuals of Chinese ethnicity with non-syndromic postaxial
      polydactyly. We presented the clinical features and molecular evaluations of 19
      probands. GLI3 mutations were identified in 15.8% of probands (3/19) including
      two novel frame-shift mutations c.3855dupC (p.Met1286HisfsTer18) and c.4141delA
      (p.Arg1381GlyfsTer38) detected in sporadic cases and one previously reported
      nonsense mutation (c.1927C>T/p.Arg643Ter) in a familial case. Of note, GLI3
      mutations were exclusively detected in patients with bilateral polydactyly
      affecting both hands and feet. Three out of five (60%) probands with bilateral
      polydactyly on both hands and feet carried pathogenic mutations in GLI3. Our
      study demonstrated the role of GLI3 in a significant fraction of patients with
      non-syndromic bilateral polydactyly affecting both hands and feet. 

PMID- 24667699
TI  - MALDI Orbitrap mass spectrometry for fast and simplified analysis of novel street
      and designer drugs.
AB  - BACKGROUND: New strategies of rapid high-throughput analysis of street drugs
      without time-consuming sample preparations are necessary due to the massive
      variety of illicit substances available on the market. METHODS: We used matrix
      assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry
      (HRMS) to identify substances in 74 drug samples obtained from anonymous drug
      users who participate in the drug prevention initiative "checkit!". We compared
      our methodology with results derived from "checkit!" where samples are analyzed
      by high performance liquid chromatography (HPLC) coupled to ultraviolet diode
      array detection (UV-DAD) as well as single Quad-MS. Reference substances were
      serially diluted for calibration curves to assess the possibility of obtaining
      quantitative information with MALDI using an ionic liquid matrix. RESULTS: All
      drug substances found by "checkit!" analysis were also identified by MALDI HRMS
      full scan without previous chromatographic separations, including the detection
      of additionally 16 substances not detected by "checkit!". Reference substances
      such as cocaine, lysergic acid diethylamide, levamisole and papaverine were
      detectable using the ionic liquid matrix N,N-diisopropylethylammonium alpha
      cyanohydroxycinnamate. Serial dilutions revealed correlation coefficients ranging
      from 0.95 to 0.99. CONCLUSION: Considering the growing complexity in the analysis
      of designer drugs the presented method can be used either in parallel or instead
      of already established drug identification techniques as a fast and comprehensive
      primary screening tool.

PMID- 24667700
TI  - Temporal dynamics underlying the modulation of social status on social attention.
AB  - Fixating someone suddenly moving the eyes is known to trigger a corresponding
      shift of attention in the observer. This phenomenon, known as gaze-cueing effect,
      can be modulated as a function of the social status of the individual depicted in
      the cueing face. Here, in two experiments, we investigated the temporal dynamics
      underlying this modulation. To this end, a gaze-cueing paradigm was implemented
      in which centrally-placed faces depicting high- and low-status individuals
      suddenly shifted the eyes towards a location either spatially congruent or
      incongruent with that occupied by a subsequent target stimulus. Social status was
      manipulated by presenting fictive Curriculum Vitae before the experimental phase.
      In Experiment 1, in which two temporal intervals (50 ms vs. 900 ms) occurred
      between the direct-gaze face and the averted-gaze face onsets, a stronger gaze
      cueing effect in response to high-status faces than low-status faces was
      observed, irrespective of the time participants were allowed for extracting
      social information. In Experiment 2, in which two temporal intervals (200 ms vs.
      1000 ms) occurred between the averted-gaze face and target onset, a stronger gaze
      cueing for high-status faces was observed at the shorter interval only. Taken
      together, these results suggest that information regarding social status is
      extracted from faces rapidly (Experiment 1), and that the tendency to selectively
      attend to the locations gazed by high-status individuals may decay with time
      (Experiment 2). 

PMID- 24667701
TI  - Total nitrogen concentrations in surface water of typical agro- and forest
      ecosystems in China, 2004-2009.
AB  - We assessed the total nitrogen (N) concentrations of 28 still surface water (lake
      and pond), and 42 flowing surface water (river), monitoring sites under 29
      typical terrestrial ecosystems of the Chinese Ecosystem Research Network (CERN)
      using monitoring data collected between 2004 and 2009. The results showed that
      the median total N concentrations of still surface water were significantly
      higher in the agro- (1.5 mg . L(-1)) and oasis agro- ecosystems (1.8 mg . L(-1))
      than in the forest ecosystems (1.0 mg . L(-1)). This was also the case for
      flowing surface water, with total N concentrations of 2.4 mg . L(-1), 1.8 mg . L(
      1) and 0.5 mg . L(-1) for the agro-, oasis agro- and forest ecosystems,
      respectively. In addition, more than 50% of the samples in agro- and oasis agro-
      ecosystems were seriously polluted (>1.0 mg . L(-1)) by N. Spatial analysis
      showed that the total N concentrations in northern and northwestern regions were
      higher than those in the southern region for both still and flowing surface
      waters under agro- and oasis agro- ecosystems, with more than 50% of samples
      exceeding 1.0 mg . L(-1) (the Class III limit of the Chinese National Quality
      Standards for Surface Waters) in surface water in the northern region. Nitrogen
      pollution in agro- ecosystems is mainly due to fertilizer applications, while the
      combination of fertilizer and irrigation exacerbates nitrogen pollution in oasis
      agro- ecosystems.

PMID- 24667702
TI  - Achieving optimum mechanical performance in metallic nanolayered Cu/X (X = Zr,
      Cr) micropillars.
AB  - The selection and design of modern high-performance structural engineering
      materials such as nanostructured metallic multilayers (NMMs) is driven by
      optimizing combinations of mechanical properties and requirements for predictable
      and noncatastrophic failure in service. Here, the Cu/X (X = Zr, Cr) nanolayered
      micropillars with equal layer thickness (h) spanning from 5-125 nm are uniaxially
      compressed and it is found that these NMMs exhibit a maximum strain hardening
      capability and simultaneously display a transition from bulk-like to small-volume
      materials behavior associated with the strength at a critical intrinsic size h ~
      20 nm. We develop a deformation mode-map to bridge the gap between the interface
      characteristics of NMMs and their failure phenomena, which, as shrinking the
      intrinsic size, transit from localized interface debonding/extrusion to interface
      shearing. Our findings demonstrate that the optimum robust performance can be
      achieved in NMMs and provide guidance for their microstructure sensitive design
      for performance optimization.

PMID- 24667703
TI  - Bone marrow mesenchymal stem cells promote the repair of islets from diabetic
      mice through paracrine actions.
AB  - Transplantation of bone marrow mesenchymal stem cells (MSCs) has been shown to
      effectively lower blood glucose levels in diabetic individuals, but the mechanism
      has not been adequately explained. We hypothesized that MSCs exert beneficial
      paracrine actions on the injured islets by releasing biologically active factors.
      To prove our hypothesis, we tested the cytoprotective effect of conditioned
      medium from cultured MSCs on isolated islets exposed to STZ in vitro and on mice
      islets after the experimental induction of diabetes in vivo. We assessed islet
      regeneration in the presence of conditioned medium and explored the possible
      mechanisms involved. Transplantation of MSCs can ameliorate hyperglycemia in
      diabetic mice by promoting the regeneration of beta cells. Both beta cell
      replication and islet progenitors differentiation contribute to beta cell
      regeneration. MSC transplantation resulted in increases in pAkt and pErk
      expression by islets in vivo. Treatment with MSC-CM promoted islet cell
      proliferation and resulted in increases in pAkt and pErk expression by islets in
      vitro. The MSC-CM-mediated induction of beta cell proliferation was completely
      blocked by the PI3K/Akt inhibitor LY294002 but not by the MEK/Erk inhibitor
      PD98059. Together, these data suggest that the PI3K/Akt signal pathway plays a
      critical role in beta cell proliferation after MSC transplantation. 

PMID- 24667704
TI  - Making de-extinction mundane?

PMID- 24667705
TI  - The pathogen Candida albicans hijacks pyroptosis for escape from macrophages.
AB  - The fungal pathogen Candida albicans causes macrophage death and escapes, but the
      molecular mechanisms remained unknown. Here we used live-cell imaging to monitor
      the interaction of C. albicans with macrophages and show that C. albicans kills
      macrophages in two temporally and mechanistically distinct phases. Early upon
      phagocytosis, C. albicans triggers pyroptosis, a proinflammatory macrophage
      death. Pyroptosis is controlled by the developmental yeast-to-hypha transition of
      Candida. When pyroptosis is inactivated, wild-type C. albicans hyphae cause
      significantly less macrophage killing for up to 8 h postphagocytosis. After the
      first 8 h, a second macrophage-killing phase is initiated. This second phase
      depends on robust hyphal formation but is mechanistically distinct from
      pyroptosis. The transcriptional regulator Mediator is necessary for morphogenesis
      of C. albicans in macrophages and the establishment of the wild-type surface
      architecture of hyphae that together mediate activation of macrophage cell death.
      Our data suggest that the defects of the Mediator mutants in causing macrophage
      death are caused, at least in part, by reduced activation of pyroptosis. A
      Mediator mutant that forms hyphae of apparently wild-type morphology but is
      defective in triggering early macrophage death shows a breakdown of cell surface
      architecture and reduced exposed 1,3 beta-glucan in hyphae. Our report shows how
      Candida uses host and pathogen pathways for macrophage killing. The current model
      of mechanical piercing of macrophages by C. albicans hyphae should be revised to
      include activation of pyroptosis by hyphae as an important mechanism mediating
      macrophage cell death upon C. albicans infection. IMPORTANCE Upon phagocytosis by
      macrophages, Candida albicans can transition to the hyphal form, which causes
      macrophage death and enables fungal escape. The current model is that the highly
      polarized growth of hyphae results in macrophage piercing. This model is
      challenged by recent reports of C. albicans mutants that form hyphae of wild-type
      morphology but are defective in killing macrophages. We show that C. albicans
      causes macrophage cell death by at least two mechanisms. Phase 1 killing (first 6
      to 8 h) depends on the activation of the pyroptotic programmed host cell death by
      fungal hyphae. Phase 2 (up to 24 h) is rapid and depends on robust hyphal
      formation but is independent of pyroptosis. Our data provide a new model for how
      the interplay between fungal morphogenesis and activation of a host cell death
      pathway mediates macrophage killing by C. albicans hyphae.

PMID- 24667706
TI  - A mouse model for Betacoronavirus subgroup 2c using a bat coronavirus strain HKU5
      variant.
AB  - Cross-species transmission of zoonotic coronaviruses (CoVs) can result in
      pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV),
      identified in 2012, has caused 182 cases to date, with ~43% mortality, and no
      small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus
      (BtCoV) strain HKU5 of Betacoronavirus (beta-CoV) subgroup 2c share >65% identity
      at the amino acid level in several regions, including nonstructural protein 5
      (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine
      targets. BtCoV HKU5 has been described in silico but has not been shown to
      replicate in culture, thus hampering drug and vaccine studies against subgroup 2c
      beta-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5
      containing the severe acute respiratory syndrome (SARS)-CoV spike (S)
      glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in
      cell culture and in young and aged mice, where the virus targets airway and
      alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit
      a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and
      MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle
      (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE
      challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence,
      causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation
      in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14,
      open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor
      active against the nsp5 proteases of subgroup 2c beta-CoVs. Synthetic-genome
      platforms capable of reconstituting emerging zoonotic viral pathogens or their
      phylogenetic relatives provide new strategies for identifying broad-based
      therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis.
      IMPORTANCE The 2012 outbreak of MERS-CoV raises the specter of another global
      epidemic, similar to the 2003 SARS-CoV epidemic. MERS-CoV is related to BtCoV
      HKU5 in target regions that are essential for drug and vaccine testing. Because
      no small animal model exists to evaluate MERS-CoV pathogenesis or to test
      vaccines, we constructed a recombinant BtCoV HKU5 that expressed a region of the
      SARS-CoV spike (S) glycoprotein, thereby allowing the recombinant virus to grow
      in cell culture and in mice. We show that this recombinant virus targets airway
      epithelial cells and causes disease in aged mice. We use this platform to (i)
      identify a broad-spectrum antiviral that can potentially inhibit viruses closely
      related to MERS-CoV, (ii) demonstrate the absence of increased eosinophilic
      immune pathology for MERS-CoV N protein-based vaccines, and (iii) mouse adapt
      this virus to identify viral genetic determinants of cross-species transmission
      and virulence. This study holds significance as a strategy to control newly
      emerging viruses.

PMID- 24667707
TI  - Coupling between protein level selection and codon usage optimization in the
      evolution of bacteria and archaea.
AB  - The relationship between the selection affecting codon usage and selection on
      protein sequences of orthologous genes in diverse groups of bacteria and archaea
      was examined by using the Alignable Tight Genome Clusters database of prokaryote
      genomes. The codon usage bias is generally low, with 57.5% of the gene-specific
      optimal codon frequencies (Fopt) being below 0.55. This apparent weak selection
      on codon usage contrasts with the strong purifying selection on amino acid
      sequences, with 65.8% of the gene-specific dN/dS ratios being below 0.1. For most
      of the genomes compared, a limited but statistically significant negative
      correlation between Fopt and dN/dS was observed, which is indicative of a link
      between selection on protein sequence and selection on codon usage. The strength
      of the coupling between the protein level selection and codon usage bias showed a
      strong positive correlation with the genomic GC content. Combined with previous
      observations on the selection for GC-rich codons in bacteria and archaea with GC
      rich genomes, these findings suggest that selection for translational fine-tuning
      could be an important factor in microbial evolution that drives the evolution of
      genome GC content away from mutational equilibrium. This type of selection is
      particularly pronounced in slowly evolving, "high-status" genes. A significantly
      stronger link between the two aspects of selection is observed in free-living
      bacteria than in parasitic bacteria and in genes encoding metabolic enzymes and
      transporters than in informational genes. These differences might reflect the
      special importance of translational fine-tuning for the adaptability of gene
      expression to environmental changes. The results of this work establish the
      coupling between protein level selection and selection for translational
      optimization as a distinct and potentially important factor in microbial
      evolution. IMPORTANCE Selection affects the evolution of microbial genomes at
      many levels, including both the structure of proteins and the regulation of their
      production. Here we demonstrate the coupling between the selection on protein
      sequences and the optimization of codon usage in a broad range of bacteria and
      archaea. The strength of this coupling varies over a wide range and strongly and
      positively correlates with the genomic GC content. The cause(s) of the evolution
      of high GC content is a long-standing open question, given the universal
      mutational bias toward AT. We propose that optimization of codon usage could be
      one of the key factors that determine the evolution of GC-rich genomes. This work
      establishes the coupling between selection at the level of protein sequence and
      at the level of codon choice optimization as a distinct aspect of genome
      evolution.

PMID- 24667708
TI  - Comparison of widely used Listeria monocytogenes strains EGD, 10403S, and EGD-e
      highlights genomic variations underlying differences in pathogenicity.
AB  - For nearly 3 decades, listeriologists and immunologists have used mainly three
      strains of the same serovar (1/2a) to analyze the virulence of the bacterial
      pathogen Listeria monocytogenes. The genomes of two of these strains, EGD-e and
      10403S, were released in 2001 and 2008, respectively. Here we report the genome
      sequence of the third reference strain, EGD, and extensive genomic and phenotypic
      comparisons of the three strains. Strikingly, EGD-e is genetically highly
      distinct from EGD (29,016 single nucleotide polymorphisms [SNPs]) and 10403S
      (30,296 SNPs), and is more related to serovar 1/2c than 1/2a strains. We also
      found that while EGD and 10403S strains are genetically very close (317 SNPs),
      EGD has a point mutation in the transcriptional regulator PrfA (PrfA*), leading
      to constitutive expression of several major virulence genes. We generated an EGD
      e PrfA* mutant and showed that EGD behaves like this strain in vitro, with slower
      growth in broth and higher invasiveness in human cells than those of EGD-e and
      10403S. In contrast, bacterial counts in blood, liver, and spleen during
      infection in mice revealed that EGD and 10403S are less virulent than EGD-e,
      which is itself less virulent than EGD-e PrfA*. Thus, constitutive expression of
      PrfA-regulated virulence genes does not appear to provide a significant advantage
      to the EGD strain during infection in vivo, highlighting the fact that in vitro
      invasion assays are not sufficient for evaluating the pathogenic potential of L.
      monocytogenes strains. Together, our results pave the way for deciphering
      unexplained differences or discrepancies in experiments using different L.
      monocytogenes strains. IMPORTANCE Over the past 3 decades, Listeria has become a
      model organism for host-pathogen interactions, leading to critical discoveries in
      a broad range of fields, including bacterial gene regulation, cell biology, and
      bacterial pathophysiology. Scientists studying Listeria use primarily three
      pathogenic strains: EGD, EGD-e, and 10403S. Despite many studies on EGD, it is
      the only one of the three strains whose genome has not been sequenced. Here we
      report the sequence of its genome and a series of important genomic and
      phenotypic differences between the three strains, in particular, a critical
      mutation in EGD's PrfA, the main regulator of Listeria virulence. Our results
      show that the three strains display differences which may play an important role
      in the virulence differences observed between the strains. Our findings will be
      of critical relevance to listeriologists and immunologists who have used or may
      use Listeria as a tool to study the pathophysiology of listeriosis and immune
      responses.

PMID- 24667709
TI  - A Poly-N-acetylglucosamine-Shiga toxin broad-spectrum conjugate vaccine for Shiga
      toxin-producing Escherichia coli.
AB  - Many pathogens produce the beta-(1-6)-linked poly-N-acetylglucosamine (PNAG)
      surface polysaccharide that is being developed as a broadly protective
      antimicrobial vaccine. However, it is unknown whether systemically injected PNAG
      vaccines or antibodies would provide protective immunity against pathogens
      confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing
      Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens
      for which effective immunotherapeutics are lacking. To ascertain whether systemic
      IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a
      synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin
      1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the
      conjugate vaccine were tested for bacterial killing and toxin neutralization in
      vitro and protection against infection in infant mice. Cell surface PNAG was
      detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including
      E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1
      potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies
      elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and
      bactericidal activity. Following intraperitoneal injection, antibodies to both
      PNAG and Stx were needed for infant mouse protection against O157 STEC. These
      antibodies also mediated protection against the Stx2-producing O104:H4 strain
      that was the cause of a recent outbreak in Germany, although sufficient doses of
      antibody to PNAG alone were protective against this strain in infant mice. Our
      observations suggest that vaccination against both PNAG and Stx, using a
      construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective
      against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N
      acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this
      one structure with a multispecies vaccine. Whether antibodies to PNAG can protect
      against pathogens confined to the gastrointestinal tract is not known. As Shiga
      toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of
      infection whose virulence is dependent on elaboration of Stx, we prepared a
      vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga
      toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin
      neutralization, and protective efficacy in infant mice. All nine (100%) clinical
      strains of STEC from different serogroups expressed PNAG. Vaccine-induced
      antibody mediated in vitro killing of STEC and neutralization of both Stx1 and
      Stx2. Passive administration of antibody to the conjugate showed protection
      requiring immunity to both PNAG and Stx for O157 strains, although for an O104
      strain, antibody to PNAG alone was protective. Immunity to PNAG may contribute to
      protection against STEC infections.

PMID- 24667711
TI  - Is virology dead?

PMID- 24667712
TI  - The effects of minocycline or riluzole treatment on spinal root avulsion-induced
      pain in adult rats.
AB  - Spinal root avulsion produces tactile and thermal hypersensitivity,
      neurodegeneration, and microglial and astrocyte activation in both the
      deafferented and the adjacent intact spinal cord segments. Following avulsion of
      the fifth lumbar spinal root, immediate and prolonged treatment with riluzole or
      minocycline for 2 weeks altered the development of behavioral hypersensitivity.
      Riluzole delayed the onset of thermal and tactile hypersensitivity and partially
      reversed established pain behavior. Minocycline effectively prevented and
      reversed both types of behavioral change. Histologic analysis revealed that both
      drugs reduced microglial staining in the spinal cord, with minocycline being more
      effective than riluzole. Astrocyte activation was ameliorated to a lesser extent.
      Surprisingly, neither drug provided a neuroprotective effect on avulsed
      motoneurons. PERSPECTIVE: Immediate treatment of spinal root avulsion injuries
      with minocycline or riluzole prevents the onset of evoked pain hypersensitivity
      by reducing microglial cell activation. When treatment is delayed, minocycline,
      but not riluzole, reverses pre-established hypersensitivity. Thus, these drugs
      may provide a new translational treatment option for chronic avulsion injury
      pain.

PMID- 24667713
TI  - Adverse event management in patients with advanced cancer receiving oral
      everolimus: focus on breast cancer.
AB  - BACKGROUND: Everolimus, an orally administered rapamycin analogue, inhibits the
      mammalian target of rapamycin (mTOR), a highly conserved intracellular serine
      threonine kinase that is a central node in a network of signaling pathways
      controlling cellular metabolism, growth, survival, proliferation, angiogenesis,
      and immune function. Everolimus has demonstrated substantial clinical benefit in
      randomized, controlled, phase III studies leading to approval for the treatment
      of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic
      origin, renal angiomyolipoma and subependymal giant-cell astrocytoma associated
      with tuberous sclerosis complex, as well as advanced hormone-receptor-positive
      (HR(+)) and human epidermal growth factor receptor-2-negative advanced breast
      cancer. MATERIALS AND METHODS: We discuss clinically relevant everolimus-related
      adverse events from the phase III studies, including stomatitis, noninfectious
      pneumonitis, rash, selected metabolic abnormalities, and infections, with focus
      on appropriate clinical management of these events and specific considerations in
      patients with breast cancer. RESULTS: The majority of adverse events experienced
      during everolimus therapy are of mild to moderate severity. The safety profile
      and protocols for toxicity management are well established. The class-effect
      adverse event profile observed with everolimus plus endocrine therapy in breast
      cancer is (as expected) distinct from that of endocrine therapy alone, but is
      similar to that observed with everolimus in other solid tumors. Information
      gained from the experience in other carcinomas on prompt diagnosis and treatments
      to optimize drug exposure, treatment outcomes, and patients' quality of life also
      applies to the patient population with advanced breast cancer. CONCLUSIONS: As
      with all orally administered agents, education of both physicians and patients in
      the management of adverse events for patients receiving everolimus is critical to
      achieving optimal exposure and clinical benefit. Active monitoring for early
      identification of everolimus-related adverse events combined with aggressive and
      appropriate intervention should lead to a reduction in the severity and duration
      of the event.

PMID- 24667714
TI  - High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray
      readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG
      03-04 MINDACT trial.
AB  - BACKGROUND: To investigate the correlation of TargetPrint with local and central
      immunohistochemistry/fluorescence in situ hybridization assessment of estrogen
      (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) in
      the first 800 patients enrolled in the MINDACT trial. PATIENTS AND METHODS: Data
      from local (N = 800) and central (N = 626) assessments of receptor status were
      collected and compared with TargetPrint results. RESULTS: For ER, the positive
      agreement (the percentage of central pathology positive assessments that were
      also TargetPrint/local laboratory positive) for TargetPrint in comparison to
      centralized assessment was 98% with a negative agreement (the percentage of
      central pathology negative assessments that were also TargetPrint/local
      laboratory negative) of 96%. For PgR, the positive agreement was 83% with a
      negative agreement of 92%. For HER2, the positive agreement was 75% with a
      negative agreement of 99%. Even though the local assessment showed higher
      positive agreement for PgR (89%) and higher positive agreement for HER2 (85%),
      the range of discordant local versus central assessments were as high as 6.7% for
      ER, 12.9% for PgR, and 4.3% for HER2. CONCLUSION: TargetPrint and local
      assessment of ER, PgR, and HER2 show high concordance with central assessment in
      the first 800 MINDACT patients. However, there are concerns about the higher
      discordance rates for some local sites. TargetPrint can improve the reliability
      of hormone receptor and HER2 testing for those centers with a lower rate of
      concordance with the reference laboratory, with the limitation of a positive
      agreement of 75% for HER2. TargetPrint consequently has important implications
      for treatment decisions in clinical practice and is a reliable alternative to
      local assessment for ER. CLINICAL TRIALS NUMBER: NCT00433589.

PMID- 24667715
TI  - A randomized controlled phase II trial of a novel composition of paclitaxel
      embedded into neutral and cationic lipids targeting tumor endothelial cells in
      advanced triple-negative breast cancer (TNBC).
AB  - BACKGROUND: EndoTAG-1, composed of paclitaxel embedded in liposomal membranes
      targeting tumor endothelial cells, was evaluated for safety and efficacy in
      advanced triple-negative breast cancer (TNBC). PATIENTS AND METHODS: One hundred
      and forty patients were treated with weekly EndoTAG-1 (22 mg/m(2)) plus
      paclitaxel (70 mg/m(2)), twice weekly EndoTAG-1 (2* 44 mg/m(2)), or weekly
      paclitaxel (90 mg/m(2)) for greater than or equal to four cycles (3-week
      treatment + 1-week rest) or until progression/toxicity. Primary end point was
      progression-free survival (PFS) rate evaluated centrally after four cycles of
      therapy (week 16). The study was not powered for intergroup comparisons. RESULTS:
      The PFS rate at week 16 was 59.1% [one-sided 95% CI: 45.6, infinity] on
      combination treatment, 34.2% [21.6, infinity] on EndoTAG-1, and 48.0% [30.5,
      infinity] on paclitaxel. Median PFS reached 4.2, 3.4, and 3.7 months,
      respectively. After complete treatment (week 41 analysis), median overall
      survival (OS) was 13.0, 11.9, and 13.1 months for the modified Intention-to-Treat
      (ITT) population and 15.1, 12.5, and 8.9 months for the per-protocol population,
      respectively. The clinical benefit rate was 53%, 31%, and 36% for the treatment
      groups. Safety analysis revealed known toxicities of the drugs with slight
      increases of grade 3/4 neutropenia on combination therapy. CONCLUSION: Treatment
      of advanced TNBC with a combination of EndoTAG-1 and standard paclitaxel
      [Taxol(r) (Bristol-Myers Squibb GmbH), or equivalent generic formulation] was
      well tolerated and showed antitumor efficacy. The positive trend needs to be
      confirmed in a randomized phase III trial. STUDY REGISTRATION: European Clinical
      Trials Database: EudraCT number 2006-002221-23. ClinicalTrials.gov identifier:
      NCT00448305.

PMID- 24667716
TI  - Human epidermal growth receptor-2 overexpressing early operable primary breast
      cancers in older (>=70 years) women: biology and clinical outcome in comparison
      with younger (<70 years) patients.
AB  - INTRODUCTION: There is dearth of literature reporting the prevalence and
      biological characteristics as well as the long-term clinical outcome of human
      epidermal growth factor receptor-2 (HER2) overexpressing tumours in older women.
      Currently, research involving trastuzumab at large focuses on the younger
      population. This study aimed to analyse their biological characteristics and to
      compare them with their younger counterparts from a single centre with a long
      term clinical follow-up. METHODS: Over 37 years (1973-2010), 1758 older (>=70
      years) women with early operable (<5 cm) primary breast cancer were managed in a
      dedicated clinic and have complete clinical information available. Of these, 813
      patients underwent primary surgery and 575 had good quality tumour samples
      available for tissue microarray analysis using indirect immunohistochemistry.
      Comparison was made with data from a well-characterised younger (<70 years)
      series (N = 1711) treated between 1986 and 1998 (before adjuvant trastuzumab
      became standard) in our institution. Forty five (7.6%) and 140 (8.2%) patients
      from the older and younger series, respectively, had HER2-positive tumours.
      RESULTS: HER2 overexpression was seen in 45 (7.6%) older women and 140 (8.2%) in
      younger patients (P = 0.56). HER2 overexpressing tumours in older women when
      compared with that in their younger counterparts were associated with low Ki67
      and high bcl2 expression (P < 0.05). Only 26% of the younger patients and none of
      the older patients received adjuvant chemotherapy, and no patients at the time
      received trastuzumab. However, there was no significant difference in the outcome
      of the two age groups (5-year breast cancer-specific survival rate: <70 years =
      65% versus >70 years = 70%, P = 0.51). CONCLUSION: HER2 overexpressing tumours in
      older women showed relatively a less aggressive phenotype and did not show any
      inferior long-term clinical outcome despite not having received chemotherapy when
      compared with the younger patients. The precise role of different adjuvant
      systemic therapies in this population needs to be delineated.

PMID- 24667717
TI  - Phase II study of treatment of advanced ovarian cancer with folate-receptor
      targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc
      etarfolatide).
AB  - BACKGROUND: This report examines (99m)Tc-etarfolatide imaging to identify the
      presence of folate receptor (FR) on tumors of women with recurrent/refractory
      ovarian or endometrial cancer and correlates expression with response to FR
      targeted therapy (vintafolide). PATIENTS AND METHODS: In this phase II, single
      arm, multicenter study, patients with advanced ovarian cancer were imaged with
      (99m)Tc-etarfolatide before vintafolide treatment. Up to 10 target lesions (TLs)
      were selected based on Response Evaluation Criteria In Solid Tumors criteria
      using computed tomography scans. Single-photon emission computed tomography
      images of TLs were assessed for (99m)Tc-etarfolatide uptake as either FR positive
      or negative. Patients were categorized by percentage of TLs positive and grouped
      as FR(100%), FR(10%-90%), and FR(0%). Lesion and patient response were correlated
      with etarfolatide uptake. RESULTS: Forty-nine patients were enrolled; 43 were
      available for analysis. One hundred thirty-nine lesions were (99m)Tc-etarfolatide
      evaluable: 110 FR positive and 29 FR negative. Lesion disease control rate (DCR =
      stable or response) was observed in 56.4% of FR-positive lesions versus 20.7% of
      FR-negative lesions (P < 0.001). Patient DCR was 57%, 36%, and 33% in FR(100%),
      FR(10%-90%), and FR(0%) patients, respectively. Median overall survival was 14.6,
      9.6, and 3.0 months in FR(100%), FR(10%-90%), and FR(0%) patients, respectively.
      CONCLUSIONS: Overall response to FR-targeted therapy and DCR correlate with FR
      positivity demonstrated by (99m)Tc-etarfolatide imaging. CLINICAL TRIAL NUMBER:
      NCT00507741.

PMID- 24667718
TI  - EMVI-positive stage II rectal cancer has similar clinical outcomes as stage III
      disease following pre-operative chemoradiotherapy.
AB  - BACKGROUND: Stage II rectal cancers comprise a heterogeneous group, and there is
      significant variability in practise with regards to adjuvant chemotherapy; the
      survival benefit of chemotherapy is perceived to be <4% in these patients.
      However, in recent years, the emergence of additional prognostic factors such as
      extramural venous invasion (EMVI) suggests that there may be sub-stratification
      of stage II tumours and, further, we may be under-estimating the benefit adjuvant
      chemotherapy provides in high-risk patients. This study examined the outcomes of
      patients with stage II and III rectal cancer to determine whether EMVI status
      influences disease-free survival (DFS). PATIENTS AND METHODS: An analysis of a
      prospectively maintained database was conducted of patients presenting with
      rectal cancer between 2006 and 2012. All patients underwent curative surgery and
      had no evidence of metastases at presentation. Clinicopathological factors were
      compared between stage II and III disease. The primary end point was 3-year DFS;
      univariate and multivariate analysis was carried out using Cox proportional
      hazards regression models; hazard ratios (HR) with 95% confidence intervals (CIs)
      were calculated. RESULTS: Four hundred and seventy-eight patients were included:
      233 stage II; 245 stage III. The prevalence of EMVI was 34.9%; 57 stage II
      patients (24.5%) and 110 stage III patients (44.9%). On multivariate analysis,
      only EMVI status was a significant factor for DFS. The adjusted HR for EMVI
      either alone or in combination with nodal involvement was 2.08 (95% CI 1.10-2.95)
      and 2.74 (95% CI 1.66-4.52), respectively. CONCLUSION: EMVI is an independently
      poor prognostic factor for DFS for both stage II and stage III rectal cancer.
      These results demonstrate that there is risk-stratification within stage II
      tumours which affects prognosis. When discussing the use of adjuvant chemotherapy
      with patients that have EMVI-positive stage II tumours, these results provide
      evidence for a similarly increased risk of distant failure as stage III disease
      without venous invasion.

PMID- 24667719
TI  - Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node
      positive colorectal cancer treated with cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      (CRS-HIPEC) is the preferred treatment of peritoneal carcinomatosis (PC) of
      colorectal carcinoma. Patients with positive lymph node status have worse
      survival after CRS-HIPEC, which is probably due to higher rates of systemic
      failure. In this study, we analysed the effect of administration and timing of
      systemic chemotherapy on the outcome of lymph node positive colorectal carcinoma
      patients treated with CRS-HIPEC. PATIENTS AND METHODS: A prospective database was
      reviewed to identify lymph node positive patients with PC treated with CRS-HIPEC
      within 1 year after primary tumour diagnosis between 2004 and 2012. Medical
      history of the patients was studied for the administration of perioperative
      systemic chemotherapy and follow-up. Outcome parameters were progression-free
      survival (PFS), overall survival (OS) and pattern of recurrence. RESULTS: Seventy
      three patients treated with CRS-HIPEC for PC from lymph node positive colorectal
      carcinoma were identified. Fourteen patients received pre-CRS-HIPEC chemotherapy
      only, 32 patients underwent post-CRS-HIPEC chemotherapy only, 9 patients received
      chemotherapy both pre- and post-CRS-HIPEC and 16 patients did not receive any
      systemic chemotherapy. Of the 47 patients who did not receive pre-CRS-HIPEC
      chemotherapy, 11 (23%) did not receive any chemotherapy due to major
      postoperative complications. PFS and OS were significantly higher in patients who
      received systemic chemotherapy (PFS: median 15 versus 4 months, P = 0.024; OS:
      median 30 versus 14 months, P = 0.015), although this difference was attenuated
      after adjustment for major complications. Different chemotherapy timings did not
      differ significantly in either survival or recurrence patterns. CONCLUSIONS: In
      patients with PC from lymph node positive colorectal carcinoma, perioperative
      systemic chemotherapy is associated with increased OS and PFS, although this
      difference may be partly explained by the occurrence of major postoperative
      complication; with no evidence of difference in PFS, OS and systemic recurrence
      rate by timing of systemic chemotherapy.

PMID- 24667720
TI  - Do quality of life or physical function at diagnosis predict short-term outcomes
      during intensive chemotherapy in AML?
AB  - BACKGROUND: Intensive chemotherapy (IC) used to treat acute myeloid leukemia
      (AML) is associated with toxicity, particularly in older adults. Emerging data
      suggest that baseline quality of life (QOL) and physical function may predict
      outcomes in oncology, although data in AML are limited. We investigated the
      association between baseline QOL and physical function with short-term treatment
      outcomes in adults and elderly AML patients. MATERIALS AND METHODS: We conducted
      a prospective, longitudinal study of adults (age 18+) AML patients undergoing IC.
      Before starting IC, patients completed the European Organisation for the Research
      and Treatment of Cancer (EORTC) 30-item questionnaire (QLQ-C30) and Functional
      Assessment of Cancer Therapy Fatigue subscale (FACT-Fatigue) in addition to
      physical function tests (grip strength, timed chair stands, 2-min walk test).
      Outcomes included 60-day mortality, intensive care unit (ICU) admission and
      achievement of complete remission (CR). Logistic regression was carried out to
      evaluate each outcome. RESULTS: Of the 239 patients (median age 57.5 years),
      56.7% were male and median Charlson comorbidity score was 0. Sixty-day mortality,
      ICU admission and CR occurred in 9 (3.7%), 15 (6.3%) and 167 (69.9%) patients,
      respectively. Using univariate regression, neither QOL nor physical function at
      presentation was predictive of 60-day mortality (all P > 0.05), whereas ICU
      admission (P < 0.001) and remission status at 30 days (P = 0.007) were. Fatigue
      (P = 0.004) and role functioning (P = 0.003) were predictors of ICU admission;
      QOL and physical function were not. A higher Charlson score predicted ICU
      admission (P = 0.01) and remission status (P = 0.002). The cytogenetic risk group
      was associated with achievement of CR (P = 0.02); QOL and physical function were
      not (all P > 0.05). Findings were similar when patients age 60+ were examined.
      Relationships between fatigue and role functioning with ICU admission deserve
      further exploration. CONCLUSIONS: Baseline QOL and physical function tests in
      this prospective study were not associated with short-term mortality, ICU
      admission or achievement of CR after the first cycle of chemotherapy.

PMID- 24667721
TI  - Agreement between HADS classifications and single-item screening questions for
      anxiety and depression: a cross-sectional survey of cancer patients.
AB  - BACKGROUND: We assessed agreement between reported anxiety and depression levels
      of cancer patients using (i) single self-report items and (ii) the Hospital
      Anxiety and Depression Scale (HADS). We also explored whether anxiety and
      depression assessment by (i) single self-report items or (ii) the HADS was most
      strongly associated with a preference to be offered professional assistance. The
      proportion of patients indicating that they would accept (or were currently
      using) professional support if they were experiencing anxiety or depression was
      also examined. PATIENTS AND METHODS: A consecutive sample of cancer patients
      undergoing radiotherapy at four metropolitan public hospitals in Australia
      completed a touch screen computer survey. A consecutive subsample of patients
      attending three of these treatment centres answered additional questions about
      psychological support preferences. RESULTS: Of 304 respondents, 54% [95%
      confidence interval (CI) 48% to 60%] perceived that they were currently
      experiencing mild to severe anxiety and depression. 22% (95% CI 18% to 27%)
      indicated a preference to be offered professional help. There was moderate
      agreement between the HADS and single-item responses for categorisation of
      anxiety and depression. Patient-perceived mild to severe anxiety and depression
      levels appeared to be the best measure for identifying those with a preference to
      be offered professional assistance. Of a subsample of 193 respondents, 89% (95%
      CI 84% to 93%) indicated that if they were experiencing anxiety or depression,
      they would accept (or were currently using) professional support. CONCLUSIONS:
      Single-item screening in a cancer care setting may not adequately capture
      clinical anxiety and depression. However, single-items assessing patients'
      perceived levels of anxiety and depression are useful indicators of whether
      patients want to be offered, and are likely to accept, psychosocial care.

PMID- 24667722
TI  - Factors affecting surgical management following neoadjuvant therapy in patients
      with primary HER2-positive breast cancer: results from the NeoALTTO phase III
      trial.

PMID- 24667723
TI  - Are male gender and non-adenocarcinoma histology valid prognostic factors for
      breast cancer?

PMID- 24667724
TI  - Lapatinib concentration in cerebrospinal fluid in two patients with HER2-positive
      metastatic breast cancer and brain metastases.

PMID- 24667725
TI  - Bone mineral density screening should be routine in lymphoma patients.

PMID- 24667726
TI  - Rare cancers: work in progress in Europe.

PMID- 24667727
TI  - Getting tissue out of harm's way.

PMID- 24667729
TI  - An illustration of the effect of various sources of uncertainty on DNA likelihood
      ratio calculations.
AB  - A typical assessment of the strength of forensic DNA evidence is based on a
      population genetic model and estimated allele frequencies determined from a
      population database. Some experts provide a confidence or credible interval which
      takes into account the sampling variation inherent in deriving these estimates
      from only a sample of a total population. This interval is given in conjunction
      with the statistic of interest, be it a likelihood ratio (LR), match probability,
      or cumulative probability of inclusion. Bayesian methods of addressing database
      sampling variation produce a distribution for the statistic from which the
      bound(s) of the desired interval can be determined. Population database sampling
      uncertainty represents only one of the sources of uncertainty that affects
      estimation of the strength of DNA evidence. There are other uncertainties which
      can potentially have a much larger effect on the statistic such as, those
      inherent in the value of Fst, the weights given to genotype combinations in a
      continuous interpretation model, and the composition of the relevant population.
      In this paper we model the effect of each of these sources of uncertainty on a
      likelihood ratio (LR) calculation and demonstrate how changes in the distribution
      of these parameters affect the reported value. In addition, we illustrate the
      impact the different approaches of accounting for sampling uncertainties has on
      the LR for a four person mixture. 

PMID- 24667730
TI  - Enhanced adult neurogenesis increases brain stiffness: in vivo magnetic resonance
      elastography in a mouse model of dopamine depletion.
AB  - The mechanical network of the brain is a major contributor to neural health and
      has been recognized by in vivo magnetic resonance elastography (MRE) to be highly
      responsive to diseases. However, until now only brain softening was observed and
      no mechanism was known that reverses the common decrement of neural elasticity
      during aging or disease. We used MRE in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine hydrochloride (MPTP) mouse model for dopaminergic
      neurodegeneration as observed in Parkinson's disease (PD) to study the mechanical
      response of the brain on adult hippocampal neurogenesis as a robust correlate of
      neuronal plasticity in healthy and injured brain. We observed a steep transient
      rise in elasticity within the hippocampal region of up to over 50% six days after
      MPTP treatment correlating with increased neuronal density in the dentate gyrus,
      which could not be detected in healthy controls. Our results provide the first
      indication that new neurons reactively generated following neurodegeneration
      substantially contribute to the mechanical scaffold of the brain. Diagnostic
      neuroimaging may thus target on regions of the brain displaying symptomatically
      elevated elasticity values for the detection of neuronal plasticity following
      neurodegeneration. 

PMID- 24667732
TI  - The outcomes of a school-based intervention for depressive symptoms in
      adolescents do not echo the promising findings of earlier studies.

PMID- 24667733
TI  - Developing accuracy when estimating Global Burden of Disease (GBD) in mental and
      substance use disorders using complex research methodology, refined data analysis
      and community participation.

PMID- 24667731
TI  - The orally available, synthetic ether lipid edelfosine inhibits T cell
      proliferation and induces a type I interferon response.
AB  - The drug edelfosine is a synthetic analog of 2-lysophosphatidylcholine.
      Edelfosine is incorporated by highly proliferating cells, e.g. activated immune
      cells. It acts on cellular membranes by selectively aggregating the cell death
      receptor Fas in membrane rafts and interference with phosphatidylcholine (PC)
      synthesis with subsequent induction of apoptosis. Edelfosine has been proposed
      for the treatment of autoimmune diseases like multiple sclerosis (MS). Earlier
      studies on the animal model of MS, experimental autoimmune encephalomyelitis
      (EAE), have generated first evidence for the efficacy of edelfosine treatment.
      However, it is unknown if the previously described mechanisms for edelfosine
      action, which are derived from in vitro studies, are solely responsible for the
      amelioration of EAE or if edelfosine may exert additional effects, which may be
      beneficial in the context of autoimmunity. Since it was the purpose of our
      studies to assess the potential usefulness of edelfosine for the treatment of MS,
      we examined its mechanism/s of action on immune functions in human T cells. Low
      doses of edelfosine led to a decrease in homeostatic proliferation, and further
      studies of the mechanism/s of action by genome-wide transcriptional profiling
      showed that edelfosine reduces the expression of MHC class II molecules, of
      molecules involved in MHC class II-associated processing and presentation, and
      finally upregulated a series of type I interferon-associated genes. The
      inhibition of homeostatic proliferation, as well as the effects on MHC class II
      expression and -presentation, and the induction of type I interferon-associated
      genes are novel and interesting in the context of developing edelfosine for
      clinical use in MS and possibly also other T cell-mediated autoimmune diseases. 

PMID- 24667734
TI  - Self-assembled hydrogel fibers for sensing the multi-compartment intracellular
      milieu.
AB  - Targeted delivery of drugs and sensors into cells is an attractive technology
      with both medical and scientific applications. Existing delivery vehicles are
      generally limited by the complexity of their design, dependence on active
      transport, and inability to function within cellular compartments. Here, we
      developed self-assembled nanofibrous hydrogel fibers using a biologically inert,
      low-molecular-weight amphiphile. Self-assembled nanofibrous hydrogels offer
      unique physical/mechanical properties and can easily be loaded with a diverse
      range of payloads. Unlike commercially available E. coli membrane particles
      covalently bound to the pH reporting dye pHrodo, pHrodo encapsulated in self
      assembled hydrogel-fibers internalizes into macrophages at both physiologic (37
      degrees C) and sub-physiologic (4 degrees C) temperatures through an energy
      independent, passive process. Unlike dye alone or pHrodo complexed to E. coli,
      pHrodo-SAFs report pH in both the cytoplasm and phagosomes, as well the nucleus.
      This new class of materials should be useful for next-generation sensing of the
      intracellular milieu. 

PMID- 24667735
TI  - Novel neurofibromatosis type 2 mutation presenting with status epilepticus.
AB  - Neurofibromatosis type 2 (NF2) is a dominantly inherited syndrome caused by
      mutations of the tumour-suppressor NF2, which encodes the merlin protein.
      Mutations are associated with a predisposition to development of benign tumours
      in the central nervous system. Even though cerebral cortical lesions are
      frequently associated with seizures, epilepsy is rarely described in NF2. Here,
      we describe an adult case of NF2 in which the onset of symptoms was characterised
      by status epilepticus. In this patient, we identified the novel
      c.428_430delCTTdel mutation in NF2, involving the amino-terminal FERM domain,
      which is fundamental for the correct tumour suppressor function of the protein.
      Bioinformatic analyses revealed an important structural perturbation of the FERM
      domain, with a predicted impairment of the anti-tumour activity. 

PMID- 24667736
TI  - Chemotactic chemokines are important in the pathogenesis of irritable bowel
      syndrome.
AB  - Irritable bowel syndrome (IBS) is one of the most frequently diagnosed disorders,
      affecting about 20% of the general population in Western countries. This syndrome
      poses an enormous socio-economic burden, impairs the quality of life
      substantially, and increases healthcare costs. IBS can be classified as either
      idiopathic (ID-IBS) with unknown etiology or post-infectious (PI-IBS), which
      develops after a bout of acute diarrhea or gastroenteritis. Little is known about
      the immunopathogenesis of these two forms of IBS. We evaluated various biomarkers
      in clinical samples of ID-IBS and PI-IBS patients with the goal to test the
      hypothesis that the immunologic presentations of these forms of IBS are similar,
      despite their apparent different etiologic origins. Sera and stool samples from
      PI-IBS, ID-IBS, and healthy volunteers were analyzed for relative amounts of 36
      different biomarkers using the Proteome Profiler Human Cytokine Array Panel A Kit
      and quantitative ELISA. Our results demonstrated significantly high levels of
      chemotactic chemokines monocytes chemotactic protein-1 (CCL2) [p-value  = 0.003],
      macrophage inflammatory protein-1beta (CCL4) [p-value  = 0.010], and CXCL16 (p
      value 0.001) in the sera and stools of both ID-IBS and PI-IBS patients.
      Furthermore, pro-inflammatory cytokines (IFN-gamma, IL-1beta, and TNF-alpha) were
      significantly higher in IBS patients. Anti-inflammatory cytokines (IL-10, IL-4,
      and IL-13) were variable except IL-10, which was significantly higher in the
      healthy volunteers than the IBS patients. Remarkably, the amounts and expression
      pattern of these biomarkers were not significantly different between ID-IBS and
      PI-IBS. Thus, ID-IBS and PI-IBS present similar immunologic and clinical
      phenotypes, in spite of their different etiologic origins.

PMID- 24667737
TI  - Atypical cases of scleroderma en coup de sabre.
AB  - Scleroderma en coup de sabre typically presents with a cutaneous induration, but
      involvement of the underlying bone, eye, and brain is common. We report on 4
      pediatric cases with atypical initial clinical presentations. All cases were seen
      at the University of California San Francisco. Patients 1 and 2 presented to the
      Pediatric Rheumatology Clinic with uveitis and orbital pseudotumor in December
      2009 and March 2010, respectively. Patients 3 and 4 were mimicking acquired
      demyelinating disorders of the brain, acute demyelinating encephalomyelitis and
      multiple sclerosis, and were referred to the Pediatric Multiple Sclerosis center
      in 2008. 

PMID- 24667738
TI  - The burden of subependymal giant cell astrocytomas associated with tuberous
      sclerosis complex: results of a patient and caregiver survey.
AB  - Tuberous sclerosis complex is a genetic disorder characterized by benign tumor
      growth including lesions in the ventricular system of the brain known as
      subependymal giant cell astrocytomas. This analysis focuses on the clinical
      presentation, management, and associated burden of subependymal giant cell
      astrocytomas in patients with tuberous sclerosis complex in the United States. An
      institutional review board-approved web-based survey of tuberous sclerosis
      complex patients and caregivers collected information, and descriptive analyses
      were conducted on age-based subgroups. A total of 116 tuberous sclerosis complex
      subependymal giant cell astrocytoma patients or caregivers responded (17% of the
      total tuberous sclerosis complex sample). Mean and median patient ages were 25.5
      and 23.5 years. Besides subependymal giant cell astrocytomas, patients also
      experienced skin lesions (72%), seizures (65%), and cognitive concerns (60%).
      Forty-five percent reported having brain surgery (22% for subependymal giant cell
      astrocytoma). In the past year, 42% of patients were admitted at least once to
      the hospital whereas 39% went to the emergency department. Results demonstrate
      that tuberous sclerosis complex-subependymal giant cell astrocytoma is associated
      with significant clinical burden, resource utilization, and decreased well-being.

PMID- 24667739
TI  - Rescue of the Friedreich ataxia knockout mutation in transgenic mice containing
      an FXN-EGFP genomic reporter.
AB  - Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by
      neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat
      expansion in the first intron of the FXN gene results in the inhibition of gene
      expression and an insufficiency of the mitochondrial protein frataxin. We
      previously generated BAC-based transgenic mice containing an FXN-EGFP genomic
      reporter construct in which the EGFP gene is fused in-frame immediately following
      the final codon of exon 5a of the human FXN gene. These transgenic mice were
      mated with mice heterozygous for a knockout mutation of the murine Fxn gene, to
      generate mice homozygous for the Fxn knockout mutation and hemizygous or
      homozygous for the human transgene. Rescue of the embryonic lethality that is
      associated with homozygosity for the Fxn knockout mutation was observed. Rescue
      mice displayed normal behavioral and histological parameters with normal
      viability, fertility and life span and without any signs of aberrant phenotype.
      Immunoblotting demonstrated the production of full-length frataxin-EGFP fusion
      protein that appears to act as a bifunctional hybrid protein. This study shows
      frataxin replacement may be a viable therapeutic option. Further, these mice
      should provide a useful resource for the study of human FXN gene expression,
      frataxin function, the evaluation of pharmacologic inducers of FXN expression in
      a whole-animal model and provide a useful source of cells for stem cell
      transplantation studies. 

PMID- 24667740
TI  - Blood alpha-tocopherol, gamma-tocopherol levels and risk of prostate cancer: a
      meta-analysis of prospective studies.
AB  - BACKGROUND: Epidemiological studies that have examined the association of blood
      alpha-tocopherol and gamma-tocopherol (the principal bioactive form of vitamin E)
      levels with the risk of prostate cancer have yielded inconsistent results. In
      addition, a quantitative assessment of published studies is not available.
      METHODS AND FINDINGS: In this meta-analysis, relevant studies were sought by a
      search of the PubMed and Embase databases for articles published up to October
      2013, with no restrictions. Bibliographies from retrieved articles also were
      scoured to find further eligible studies. Prospective studies that reported
      adjusted relative risk (RR) estimates with 95% confidence intervals (CIs) for the
      association between blood tocopherol levels and the risk of prostate cancer were
      included. Nine nested case-control studies involving approximately 370,000
      participants from several countries were eligible. The pooled RRs of prostate
      cancer for the highest versus lowest category of blood alpha-tocopherol levels
      were 0.79 (95% CI: 0.68-0.91), and those for gamma-tocopherol levels were 0.89
      (95% CI: 0.71-1.12), respectively. Significant heterogeneity was present among
      the studies in terms of blood gamma-tocopherol levels (p = 0.008) but not in
      terms of blood alpha-tocopherol levels (p = 0.33). The risk of prostate cancer
      decreased by 21% for every 25-mg/L increase in blood alpha-tocopherol levels (RR:
      0.79; 95% CI: 0.69-0.91). CONCLUSIONS: Blood alpha-tocopherol levels, but not
      gamma-tocopherol levels, were inversely associated with the risk of prostate
      cancer in this meta-analysis.

PMID- 24667741
TI  - Case report: Long-standing complex regional pain syndrome relieved by a
      cephalosporin antibiotic.
AB  - We describe a young woman who had had treatment-refractory complex regional pain
      syndrome (CRPS) for 6 years before receiving antibiotic treatment with cefadroxil
      (a cephalosporin derivative) for a minor infection. Cefadroxil reduced the
      patient's pain and motor dysfunction (dystonia and impaired voluntary movement)
      within days; the pain and motor disorder returned when cefadroxil was
      discontinued; and both again abated when cefadroxil was re-instituted. The
      patient has now had symptom relief for more than 3 years on continuing cefadroxil
      therapy. We discuss this case in the context of previous reports of antibiotic
      treatment relieving neuropathic pain in experimental animals.

PMID- 24667742
TI  - Liquid crystal droplet-based amplification of microvesicles that are shed by
      mammalian cells.
AB  - Membrane-derived microvesicles (MVs) shed by cells are being investigated for
      their role in intercellular communication and as potential biomarkers of disease,
      but facile and sensitive methods for their analysis do not exist. Here we
      demonstrate new principles for analysis of MVs that use micrometer-sized droplets
      of liquid crystals (LCs) to amplify MVs that are selectively captured via
      antibody-mediated interactions. The influence of the MVs on the micrometer-sized
      LC droplets is shown to be readily quantified via use of flow cytometry. The
      methodology was developed using MVs shed by epidermoid carcinoma A431 cells that
      contain epidermal growth factor receptor (EGFR) as an important and
      representative example of MVs containing signaling proteins that play a central
      role in cancer. The LC droplets were found to be sensitive to 10(6) MVs
      containing EGFR (relative to controls using isotype control antibody) and to
      possess a dynamic range of response across several orders of magnitude. Because
      the 100 nm-sized MVs captured via EGFR generate an optical response in the
      micrometer-sized LC droplets that can be readily detected by flow cytometry in
      light scattering mode, the approach possesses significant advantages over direct
      detection of MVs by flow cytometry. The LC droplets are also substantially more
      sensitive than techniques such as immunoblotting because the lipid-component of
      the MVs serves to amplify the antibody-mediated capture of the target proteins in
      the MVs. Other merits of the approach are defined and discussed in the paper. 

PMID- 24667743
TI  - Endoscopic extraction of a prevertebral migrated guidewire after posterior
      cervical instrumentation.

PMID- 24667744
TI  - Limitations of the spike-triggered averaging for estimating motor unit twitch
      force: a theoretical analysis.
AB  - Contractile properties of human motor units provide information on the force
      capacity and fatigability of muscles. The spike-triggered averaging technique
      (STA) is a conventional method used to estimate the twitch waveform of single
      motor units in vivo by averaging the joint force signal. Several limitations of
      this technique have been previously discussed in an empirical way, using
      simulated and experimental data. In this study, we provide a theoretical analysis
      of this technique in the frequency domain and describe its intrinsic limitations.
      By analyzing the analytical expression of STA, first we show that a certain
      degree of correlation between the motor unit activities prevents an accurate
      estimation of the twitch force, even from relatively long recordings. Second, we
      show that the quality of the twitch estimates by STA is highly related to the
      relative variability of the inter-spike intervals of motor unit action
      potentials. Interestingly, if this variability is extremely high, correct
      estimates could be obtained even for high discharge rates. However, for
      physiological inter-spike interval variability and discharge rate, the technique
      performs with relatively low estimation accuracy and high estimation variance.
      Finally, we show that the selection of the triggers that are most distant from
      the previous and next, which is often suggested, is not an effective way for
      improving STA estimates and in some cases can even be detrimental. These results
      show the intrinsic limitations of the STA technique and provide a theoretical
      framework for the design of new methods for the measurement of motor unit force
      twitch. 

PMID- 24667746
TI  - Bovine exome sequence analysis and targeted SNP genotyping of recessive fertility
      defects BH1, HH2, and HH3 reveal a putative causative mutation in SMC2 for HH3.
AB  - The recent discovery of bovine haplotypes with negative effects on fertility in
      the Brown Swiss, Holstein, and Jersey breeds has allowed producers to identify
      carrier animals using commercial single nucleotide polymorphism (SNP) genotyping
      assays. This study was devised to identify the causative mutations underlying
      defective bovine embryo development contained within three of these haplotypes
      (Brown Swiss haplotype 1 and Holstein haplotypes 2 and 3) by combining exome
      capture with next generation sequencing. Of the 68,476,640 sequence variations
      (SV) identified, only 1,311 genome-wide SNP were concordant with the haplotype
      status of 21 sequenced carriers. Validation genotyping of 36 candidate SNP
      identified only 1 variant that was concordant to Holstein haplotype 3 (HH3),
      while no variants located within the refined intervals for HH2 or BH1 were
      concordant. The variant strictly associated with HH3 is a non-synonymous SNP
      (T/C) within exon 24 of the Structural Maintenance of Chromosomes 2 (SMC2) on
      Chromosome 8 at position 95,410,507 (UMD3.1). This polymorphism changes amino
      acid 1135 from phenylalanine to serine and causes a non-neutral, non-tolerated,
      and evolutionarily unlikely substitution within the NTPase domain of the encoded
      protein. Because only exome capture sequencing was used, we could not rule out
      the possibility that the true causative mutation for HH3 might lie in a non
      exonic genomic location. Given the essential role of SMC2 in DNA repair,
      chromosome condensation and segregation during cell division, our findings
      strongly support the non-synonymous SNP (T/C) in SMC2 as the likely causative
      mutation. The absence of concordant variations for HH2 or BH1 suggests either the
      underlying causative mutations lie within a non-exomic region or in exome regions
      not covered by the capture array. 

PMID- 24667745
TI  - Primary human alveolar bone cells isolated from tissue samples acquired at
      periodontal surgeries exhibit sustained proliferation and retain osteogenic
      phenotype during in vitro expansion.
AB  - OBJECTIVES: Bone tissue regeneration requires a source of viable, proliferative
      cells with osteogenic differentiation capacity. Periodontal surgeries represent
      an opportunity to procure small amounts of autologous tissues for primary cell
      isolation. Our objective was to assess the potential of human alveolar bone as a
      source of autologous osteogenic cells for tissue engineering and biomaterials and
      drug testing studies. MATERIALS AND METHODS: Alveolar bone tissue was obtained
      from 37 patients undergoing routine periodontal surgery. Tissue harvesting and
      cell isolation procedures were optimized to isolate viable cells. Primary cells
      were subcultured and characterized with respect to their growth characteristics,
      gene expression of osteogenic markers, alkaline phosphatase activity and matrix
      mineralization, under osteogenic stimulation. RESULTS: Alveolar bone cells were
      successfully isolated from 28 of the 30 samples harvested with bone forceps, and
      from 2 of the 5 samples obtained by bone drilling. The yield of cells in primary
      cultures was variable between the individual samples, but was not related to the
      site of tissue harvesting and the patient age. In 80% of samples (n = 5), the
      primary cells proliferated steadily for eight subsequent passages, reaching
      cumulative numbers over 10(10) cells. Analyses confirmed stable gene expression
      of alkaline phosphatase, osteopontin and osteocalcin in early and late cell
      passages. In osteogenic medium, the cells from late passages increased alkaline
      phosphatase activity and accumulated mineralized matrix, indicating a mature
      osteoblastic phenotype. CONCLUSIONS: Primary alveolar bone cells exhibited robust
      proliferation and retained osteogenic phenotype during in vitro expansion,
      suggesting that they can be used as an autologous cell source for bone
      regenerative therapies and various in vitro studies.

PMID- 24667747
TI  - Validation of surrogate limb analysis for body composition in children by dual
      energy X-ray absorptiometry (DXA).
AB  - BACKGROUND/OBJECTIVES: Dual energy X-ray absorptiometry (DXA) is a recognized
      tool for measurement of body composition and provides benefits of low dose
      radiation, quick scan time and multiple measurement options. Challenges arise in
      scanning children, particularly with limb movement. We aimed to validate the use
      of surrogate limb substitutions compared with whole-body scans by DXA for
      measuring fat, lean and bone mass in children. SUBJECTS/METHODS: DXA scans were
      obtained from 3-year-old children who had normal positioning and no limb movement
      (n=246) or movement of a single limb (n=55). By replacing the measurements of one
      scanned limb with those of the opposite limb, we obtained an estimate value that
      was compared with the original whole-body scan measures for fat, lean and bone
      mass, percent whole-body fat and total mass for scans without or with movement.
      RESULTS: Original normal scan analyses were highly correlated with estimates
      using substitution of the surrogate limb for all body compartments (R(2)=0.986
      0.999, P<0.005). The Bland-Altman analysis demonstrated high levels of agreement
      between the estimates using surrogate limb and original whole-body measurements.
      Differences in estimate values and variance were greater with limb substitution
      in scans with movement compared to without movement. CONCLUSIONS: Use of limb
      surrogate methodology for fat mass, lean mass, bone mineral content, percent fat
      and total mass, is a valid alternative that minimizes variation in estimates of
      body composition from DXA scans in young children in which a single limb is
      affected by movement. This will allow inclusion of scans with movement artifact
      in a single limb for data analysis.

PMID- 24667748
TI  - The impact of parenteral nutrition preparation on bloodstream infection risk and
      costs.
AB  - BACKGROUND: Catheter-related bloodstream infections (BSIs) are a serious problem
      leading to increased morbidity, longer hospital stay, and hence, additional
      costs. This study evaluated the risk of BSI and the cost of parenteral nutrition
      (PN) in Germany. SUBJECTS/METHODS: A retrospective observational chart review of
      patients hospitalized from October 2009 to April 2011 and receiving PN via ready
      to-use three-chamber bag (MCB), single bottle (SB) or hospital compounded
      admixture (CPN) was conducted across Germany. Propensity score-adjusted models
      were used to evaluate the association between the type of PN, BSI (Cox
      Proportional Hazards) and hospitalization cost (generalized linear models) within
      a subgroup receiving all three macronutrients (lipids, amino acids, glucose).
      RESULTS: Of the 1995 patient records reviewed (MCB=816; CPN=584; SB=595), 1457
      patients received all three macronutrients. After adjustment, SB was associated
      with an increased hazard of BSI, vs MCB without additions (hazard ratio (HR) (95%
      confidence interval (CI))=2.53 (1.66-3.86)) in the total cohort. Adding
      supplements to MCB on the ward also increased the BSI risk in both total and
      subgroup analyses. In patients receiving all three macronutrients, adjusted total
      costs were MCB (no additions): ?[euro]6,572 (95% CI: ?[euro]6,896-6263); CPN:
      ?[euro]6,869 (?[euro]7,283-6479); SB: ?[euro]6,872 (?[euro]7,242-6521); MCB (ward
      additions): ?[euro]7,402 (?[euro]7,878-6955); P<0.001; P<0.001. CONCLUSION: Use
      of MCB does not appear to increase treatment costs, possibly by reducing the risk
      of infection. This study identified several PN preparation methods associated
      with a significantly increased hazard for BSI; definitive CPN findings are
      limited by our inability to distinguish automated from manual pharmacy
      compounding.

PMID- 24667749
TI  - Effect of sodium alginate addition to chocolate milk on glycemia, insulin,
      appetite and food intake in healthy adult men.
AB  - BACKGROUND/OBJECTIVES: Sodium alginate reduces appetite and glycemia, when
      consumed in water- and sugar-based drinks. But, its effects when added to other
      commonly consumed beverages have not been reported. Because chocolate milk (CM)
      is criticized for raising blood glucose more than unflavored milk, the aim of our
      study was to investigate the effect of adding a strong-gelling sodium alginate to
      CM on glycemia, insulinemia, appetite and food intake. SUBJECTS/METHODS: In a
      randomized crossover design, 24 men (22.9+/-0.4 years; 22.5+/-0.3 kg/m(2)) were
      provided with isovolumetric (325 ml) treatments of CM, 1.25% alginate CM, 2.5%
      alginate CM or 2.5% alginate solution. Sodium alginate had a ratio of 0.78:1 of
      mannuronic acid (M) to guluronic acid (G) residues, and was block distributed.
      Treatments were standardized for lactose, sucrose and calcium content, and
      provided 120 min before an ad libitum pizza meal during which food intake was
      measured. Appetite and blood glucose and insulin were measured at baseline and at
      intervals pre- and post-meal. RESULTS: Addition of 2.5% alginate to CM reduced
      peak glucose concentrations, at 30 min, by an average of 6% and 13% compared with
      1.25% alginate CM (95% confidence intervals (CIs): 0.02-1.08; P=0.037) and CM
      alone (95% CIs: 0.49-1.55; P=0.000) respectively. Insulin peaks at 30 min were
      lower by 46% after 2.5% alginate CM relative to CM (95% CIs: 3.49-31.78;
      P=0.009). Pre-meal appetite was attenuated dose dependently by alginate addition
      to CM; CM with 2.5% alginate reduced mean appetite by an average of 134% compared
      with CM alone (95% CIs: 8.87-18.98; P=0.000). However, total caloric intake at
      the pizza meal did not differ among treatments. CONCLUSIONS: The addition of a
      strong-gelling sodium alginate to CM decreases pre-meal glycemia, insulinemia and
      appetite, but not caloric intake at a meal 2 h later, in healthy adult men.

PMID- 24667750
TI  - Weight loss effects from vegetable intake: a 12-month randomised controlled
      trial.
AB  - BACKGROUND/OBJECTIVES: Direct evidence for the effects of vegetable intake on
      weight loss is qualified. The study aimed to assess the effect of higher
      vegetable consumption on weight loss. SUBJECTS/METHODS: A single blind parallel
      controlled trial was conducted with 120 overweight adults (mean body mass
      index=29.98 kg/m(2)) randomised to two energy deficit healthy diet advice groups
      differing only by doubling the serving (portion) sizes of vegetables in the
      comparator group. Data were analysed as intention-to-treat using a linear mixed
      model. Spearmans rho bivariate was used to explore relationships between
      percentage energy from vegetables and weight loss. RESULTS: After 12 months, the
      study sample lost 6.5+/-5.2 kg (P<0.001 time) with no difference between groups
      (P>0.05 interaction). Both groups increased vegetable intake and lost weight in
      the first 3 months, and the change in weight was significantly correlated with
      higher proportions of energy consumed as vegetables (rho=-0.217, P=0.024).
      Fasting glucose, insulin and triglyceride levels decreased (P<0.001 time) and
      high-density lipoprotein cholesterol levels increased (P<0.001 time), with no
      difference between groups. Weight loss was sustained for 12 months by both
      groups, but the comparator group reported greater hunger satisfaction (P=0.005).
      CONCLUSIONS: Advice to consume a healthy low-energy diet leads to sustained
      weight loss, with reductions in cardiovascular disease risk factors regardless of
      an emphasis on more vegetables. In the short term, consuming a higher proportion
      of the dietary energy as vegetables may support a greater weight loss and the
      dietary pattern appears sustainable.

PMID- 24667752
TI  - The prevalence of cobalamin deficiency among vegetarians assessed by serum
      vitamin B12: a review of literature.
AB  - Individuals following vegetarian diets are at risk for developing vitamin B12
      deficiency owing to suboptimal intake. As vitamin B12 is essential for the
      synthesis of nucleic acids, erythrocytes and in the maintenance of myelin,
      deficiency may result in a variety of symptoms. Some of these symptoms may be
      severe while others may be irreversible. The objective of this review was to
      assess vitamin B12 deficiency, based on reported serum vitamin B12, among
      individuals adhering to different types of vegetarian diets. A systematic
      literature search was carried out using multiple search engines including PubMed,
      Medline, CINAHL plus, ERIC, Nursing and Allied Health Collection and
      Nursing/Academic Edition. The inclusion criteria consisted of original studies
      that assessed serum vitamin B12, studies written in English, non-case studies and
      studies that reported actual percentages of vitamin B12 deficiency. Forty
      research studies were included. The deficiency prevalence among infants reached
      45%. The deficiency among the children and adolescents ranged from 0 to 33.3%.
      Deficiency among pregnant women ranged from 17 to 39%, dependent on the
      trimester. Adults and elderly individuals had a deficiency range of 0-86.5%.
      Higher deficiency prevalence was reported in vegans than in other vegetarians.
      Thus, with few exceptions, the reviewed studies documented relatively high
      deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12
      supplements were found to be at especially high risk. Vegetarians, especially
      vegans, should give strong consideration to the use of vitamin B12 supplements to
      ensure adequate vitamin B12 intake. Vegetarians, regardless of the type of
      vegetarian diet they adhere to, should be screened for vitamin B12 deficiency. 

PMID- 24667751
TI  - Effect of sugars in solutions on subjective appetite and short-term food intake
      in 9- to 14-year-old normal weight boys.
AB  - BACKGROUND AND OBJECTIVE: The role of sugars in solutions on subjective appetite
      and food intake (FI) has received little investigation in children. Therefore, we
      examined the effect of isocaloric solutions (200 kcal/250 ml) of sugars including
      sucrose, high-fructose corn syrup-55 (HFCS) or glucose, compared with a non
      caloric sucralose control, on subjective appetite and FI in 9- to 14-year-old
      normal weight (NW) boys. PARTICIPANTS AND METHODS: NW boys (n=15) received each
      of the test solutions, in random order, 60 min before an ad libitum pizza meal.
      Subjective appetite was measured at baseline (0 min), and 15, 30, 45 and 60 min.
      RESULTS: Only glucose (P=0.003), but neither sucrose nor HFCS, reduced FI
      compared with the sucralose control. This led to a higher cumulative energy
      intake, compared with sucralose, after sucrose (P=0.009) and HFCS (P=0.01), but
      not after glucose. In all treatment sessions, subjective average appetite
      increased from baseline to 60 min, but change from baseline average appetite was
      the highest after sucrose (P<0.005). Furthermore, sucrose (r=-0.59, P=0.02) and
      HFCS (r=-0.56, P=0.03), but not glucose, were inversely associated with test meal
      FI when the treatment dose (200 kcal) was expressed on a body weight (kg) basis.
      CONCLUSIONS: Change from baseline subjective average appetite was the highest
      after sucrose, but only the glucose solution suppressed FI at the test meal 60
      min later in NW boys.

PMID- 24667753
TI  - Palmitic acid in the sn-2 position decreases glucose-dependent insulinotropic
      polypeptide secretion in healthy adults.
AB  - BACKGROUND/OBJECTIVES: Dietary triacylglycerols (TAGs) containing palmitic acid
      in the sn-2 position might impair insulin release and increase plasma glucose. We
      tested this hypothesis by comparing postprandial responses to fats with varying
      proportions of palmitic acid in the sn-2 position. SUBJECTS/METHODS: Using a
      crossover-designed randomized controlled trial in healthy men (n=25) and women
      (n=25), we compared four meals on postprandial changes in glucose (primary
      outcome), insulin, C-peptide, glucose, glucose-dependent insulinotropic
      polypeptide (GIP) and polypeptide YY (PYY) concentrations. The meals provided 14
      g protein, 85 g carbohydrate and 50 g test fat, supplied as high oleic sunflower
      (HOS) oil (control), palm olein (PO), interesterified palm olein (IPO) and lard
      containing 0.6, 9.2, 39.1 and 70.5 mol% palmitic acid at sn-2, respectively.
      RESULTS: No differences in plasma glucose, insulin and C-peptide response between
      meals were found. GIP release was lower (P<0.001) for IPO and lard compared with
      HOS and PO meals; the maximal increments (geometric mean and 95% confidence
      interval) for HOS, PO, IPO and lard were 515 (468, 569), 492 (448, 540), 398
      (350, 452) and 395 (364, 429) ng/l, respectively. There was a trend for the
      postprandial increase in PYY to be lower in women on the IPO and lard meals than
      those on the HOS and PO meals. CONCLUSIONS: Dietary TAGs with an increased
      proportion of palmitic acid in the sn-2 position do not have acute adverse
      effects on the insulin and glucose response to meals in healthy men and women,
      but they decrease GIP release.

PMID- 24667754
TI  - Body composition changes in pregnancy: measurement, predictors and outcomes.
AB  - Prevalence of overweight and obesity has risen in the United States over the past
      few decades. Concurrent with this rise in obesity has been an increase in
      pregravid body mass index and gestational weight gain affecting maternal body
      composition changes in pregnancy. During pregnancy, many of the assumptions
      inherent in body composition estimation are violated, particularly the hydration
      of fat-free mass, and available methods are unable to disentangle maternal
      composition from fetus and supporting tissues; therefore, estimates of maternal
      body composition during pregnancy are prone to error. Here we review commonly
      used and available methods for assessing body composition changes in pregnancy,
      including: (1) anthropometry, (2) total body water, (3) densitometry, (4)
      imaging, (5) dual-energy X-ray absorptiometry, (6) bioelectrical impedance and
      (7) ultrasound. Several of these methods can measure regional changes in adipose
      tissue; however, most of these methods provide only whole-body estimates of fat
      and fat-free mass. Consideration is given to factors that may influence changes
      in maternal body composition, as well as long-term maternal and offspring
      outcomes. Finally, we provide recommendations for future research in this area.

PMID- 24667755
TI  - Low molecular weight hyaluronan induces lymphangiogenesis through LYVE-1-mediated
      signaling pathways.
AB  - Hyaluronan (HA), a large nonsulfated glycosaminogycan in the extracellular
      matrix, whose degraded fragments termed as low molecular weight hyaluronan (LMW
      HA), has been reported as an important regulator of angiogenesis. However, little
      is known about the influence of LMW-HA on lymphangiogenesis. In this study, we
      try to explore the in vitro effects of LMW-HA on lymphangiogenesis and identify
      the underlying molecular mechanisms. Our results showed that LMW-HA stimulation
      significantly increased lymphatic endothelial cells (LECs) proliferation,
      migration and tube formation. Further experiments demonstrated that LMW-HA
      altered actin cytoskeleton rearrangement and increased the formation of intense
      stress fibers, lamellipodia and filopodia. Mechanistically, LMW-HA stimulation
      resulted in rapid tyrosine phosphorylation of protein kinase C alpha/betaII
      (PKCalpha/betaII) and extracellular-regulated kinase 1/2 (ERK1/2). Lymphatic
      vessel endothelial hyaluronan receptor 1 (LYVE-1), a homologue of CD44, is the
      main cell surface receptor for HA in LECs. Blocking the binding interaction of
      LMW-HA with LYVE-1 using neutralizing anti-LYVE-1 antibodies significantly
      inhibited LECs proliferation, migration, tube formation and signal transduction
      induced by LMW-HA, suggesting that LMW-HA may play a critical role in the
      processes required for lymphangiogenesis through interactions with its receptor
      LYVE-1 and triggering intracellular signal cascades.

PMID- 24667756
TI  - Study of the stability of 26 cytostatic drugs and metabolites in wastewater under
      different conditions.
AB  - The stability of 26 cytostatic drugs (21 parent compounds and 5 metabolites) in
      wastewater was studied using liquid chromatography-electrospray-tandem mass
      spectrometry (LC-ESI-MS/MS). Wastewater aliquots were spiked with the target
      compounds at 1000MUg L(-1) and stored in the dark under different temperature (
      20, 4 and 25 degrees C) and pH (acid and neutral) conditions for different
      periods of time (up to 3 months). The influence of these factors (temperature, pH
      and time) on the stability of the compounds was evaluated through an experimental
      design. The most negative factor was the time of storage, but temperature also
      exerted a very important influence. Acidification of the samples is a good option
      for some cytostatics (e.g., temozolomide, tamoxifen and its metabolites, and
      chlorambucil) but it may have a negative effect on others (e.g. ifosfamide). The
      design also showed correlations between factors indicating that an increase of
      the storage time is more relevant at high temperatures, while an increase of the
      temperature is more detrimental in non-acidified samples. After 3 months at -20
      degrees C, all compounds with the exception of temozolomide, vinorelbine,
      imatinib and erlotinib presented recoveries below 80%. The most unstable
      compounds were oxaliplatin, 5-(3-N-methyltriazen-1-yl)-imidazole-4-carboxamide
      and chlorambucil. To the authors' knowledge, the stability data reported in the
      present study is the first ever published for most of the target compounds in
      wastewater. The results obtained point out storage at -20 degrees C from
      collection to analysis as the best storage option.

PMID- 24667757
TI  - Basic fibroblast growth factor modifies the hypoxic response of human bone marrow
      stromal cells by ERK-mediated enhancement of HIF-1alpha activity.
AB  - Human bone marrow stromal cells (hBMSCs, also known as bone marrow-derived
      mesenchymal stem cells) are promising tools for the cellular therapy of human
      pathologies related to various forms of hypoxia. Although the current concepts of
      their clinical use include the expansion of hBMSC in standard cell culture
      conditions, the effect of the mitogen-driven ex vivo expansion on the adaptation
      to the hypoxic environment is unknown. Here, we provide data that the basic
      fibroblast growth factor (FGF2) enhances the induction of a wide range of hypoxia
      related adaptive genes in hypoxic hBMSCs. We identified that the FGF2 signal is
      transmitted by the ERK pathway similar to that of hypoxia that also utilises the
      distal elements of the same signalling machinery including the extracellular
      signal-regulated kinase 1/2 (ERK1/2) and mitogen-activated protein kinase kinases
      (MEK1/2) in hBMSCs. We found that the simultaneous activation of ERK1/2 by FGF2
      and hypoxia transforms the activation dynamics from oscillatory into sustained
      one. Activated ERKs co-localise with stabilised hypoxia inducible factor-1alpha
      (HIF-1alpha) followed by the reduction of its nuclear mobility as well as
      increased DNA binding capacity leading to the up-regulation of hypoxia-adaptive
      genes. Our findings indicate that the status of the ERK pathway has significant
      impacts on the molecular adaptation of hBMSCs to the hypoxic milieu. 

PMID- 24667758
TI  - Relativistic GW calculations on CH3NH3PbI3 and CH3NH3SnI3 perovskites for solar
      cell applications.
AB  - Hybrid AMX3 perovskites (A = Cs, CH3NH3; M = Sn, Pb; X = halide) have
      revolutionized the scenario of emerging photovoltaic technologies, with very
      recent results demonstrating 15% efficient solar cells. The CH3NH3PbI3/MAPb(I(1
      x)Cl(x))3 perovskites have dominated the field, while the similar CH3NH3SnI3 has
      not been exploited for photovoltaic applications. Replacement of Pb by Sn would
      facilitate the large uptake of perovskite-based photovoltaics. Despite the
      extremely fast progress, the materials electronic properties which are key to the
      photovoltaic performance are relatively little understood. Density Functional
      Theory electronic structure methods have so far delivered an unbalanced
      description of Pb- and Sn-based perovskites. Here we develop an effective GW
      method incorporating spin-orbit coupling which allows us to accurately model the
      electronic, optical and transport properties of CH3NH3SnI3 and CH3NH3PbI3,
      opening the way to new materials design. The different CH3NH3SnI3 and CH3NH3PbI3
      electronic properties are discussed in light of their exploitation for solar
      cells, and found to be dominantly due to relativistic effects. These effects
      stabilize the CH3NH3PbI3 material towards oxidation, by inducing a deeper valence
      band edge. Relativistic effects, however, also increase the material band-gap
      compared to CH3NH3SnI3, due to the valence band energy downshift (~0.7 eV) being
      only partly compensated by the conduction band downshift (~0.2 eV).

PMID- 24667759
TI  - Close the high seas to fishing?
AB  - The world's oceans are governed as a system of over 150 sovereign exclusive
      economic zones (EEZs, ~42% of the ocean) and one large high seas (HS) commons
      (~58% of ocean) with essentially open access. Many high-valued fish species such
      as tuna, billfish, and shark migrate around these large oceanic regions, which as
      a consequence of competition across EEZs and a global race-to-fish on the HS,
      have been over-exploited and now return far less than their economic potential.
      We address this global challenge by analyzing with a spatial bioeconomic model
      the effects of completely closing the HS to fishing. This policy both induces
      cooperation among countries in the exploitation of migratory stocks and provides
      a refuge sufficiently large to recover and maintain these stocks at levels close
      to those that would maximize fisheries returns. We find that completely closing
      the HS to fishing would simultaneously give rise to large gains in fisheries
      profit (>100%), fisheries yields (>30%), and fish stock conservation (>150%). We
      also find that changing EEZ size may benefit some fisheries; nonetheless, a
      complete closure of the HS still returns larger fishery and conservation outcomes
      than does a HS open to fishing. 

PMID- 24667760
TI  - Reversible neuronal and muscular toxicity of caffeine in developing vertebrates.
AB  - This study utilizes zebrafish embryos to understand the cellular and molecular
      mechanisms of caffeine toxicity in developing vertebrate embryos. By using a high
      concentration of caffeine, we observed almost all the phenotypes that have been
      described in humans and/or in other animal models, including neural tube closure
      defect, jittery, touch insensitivity, and growth retardation as well as a drastic
      coiled body phenotype. Zebrafish embryos exposed to 5mM caffeine exhibited high
      frequent movement, 10 moves/min comparing with around 3 moves/min in control
      embryos, within half an hour post exposure (HPE). They later showed twitching,
      uncoordinated movement, and eventually severe body curvature by 6HPE. Exposure at
      later stages resulted in the same phenotypes but more posteriorly. Surprisingly,
      when caffeine was removed before 6HPE, the embryos were capable of recovering but
      still exhibited mild curvature and shorter bodies. Longer exposure caused
      irreversible body curvature and lethality. These results suggest that caffeine
      likely targets the neuro-muscular physiology in developing embryos.
      Immunohistochemistry revealed that the motorneurons in treated embryos developed
      shorter axons, abnormal branching, and excessive synaptic vesicles. Developing
      skeletal muscles also appeared smaller and lacked the well-defined boundaries
      seen in control embryos. Finally, caffeine increases the expression of genes
      involved in synaptic vesicle migration. In summary, our results provide molecular
      understanding of caffeine toxicity on developing vertebrate embryos.

PMID- 24667761
TI  - Influence of copper pre-exposure on biochemical responses of the sea anemone
      Bunodosoma cangicum to changes in oxygen availability.
AB  - The influence of copper on the ability of the intertidal sea anemone Bunodosoma
      cangicum to cope with reactive oxygen species generation associated with changes
      in oxygen availability was evaluated. Sea anemones were kept under control
      condition or pre-exposed (96 h) to dissolved copper (6.1 MUg +/- 2.7 MUg/L) and
      then subjected to a 6-h period of hypoxia (0.5mg O2/L) followed by a 6-h period
      of re-oxygenation (7.5mg O2/L). Antioxidant capacity against peroxyl radicals
      (ACAP), superoxide dismutase (SOD) activity, reduced glutathione (GSH)
      concentration, lipid peroxidation (LPO) level, and ATP concentration were
      evaluated. Control sea anemones showed variations in SOD and LPO while copper pre
      exposed sea anemones displayed changes in ACAP, GSH, LPO and ATP. However, no
      clear pattern of change over time was observed. ACAP was lower in copper pre
      exposed sea anemones than in the control ones during hypoxia and recovery. SOD
      activity was increased during hypoxia and reduced shortly after recovery in
      control sea anemones. GSH concentration was higher in copper pre-exposed sea
      anemones than in the control ones in all experimental conditions. The LPO level
      increased shortly after recovery in both groups of sea anemones, being higher in
      control sea anemones than in copper pre-exposed ones. ATP concentration showed
      transient changes in copper pre-exposed sea anemones, being lower in these sea
      anemones than in control ones during recovery. These findings suggest that B.
      cangicum possess mechanisms to prevent oxidative stress generated by changes in
      oxygen availability associated with the tidal cycle, which can be disturbed by
      pre-exposure to copper.

PMID- 24667762
TI  - Aquatic animal models of human disease: selected papers from the 6th conference.

PMID- 24667763
TI  - Effects of alprazolam on cortical activity and tremors in patients with essential
      tremor.
AB  - BACKGROUND: Essential tremor (ET) is characterised by postural and action tremors
      with a frequency of 4-12 Hz. Previous studies suggest that the tremor activity
      originates in the cerebello-thalamocortical pathways. Alprazolam is a short
      acting benzodiazepine that attenuates tremors in ET. The mechanisms that mediate
      the therapeutic action of alprazolam are unknown; however, in healthy subjects,
      benzodiazepines increase cortical beta activity. In this study, we investigated
      the effect of alprazolam both on beta and tremor-related cortical activity and on
      alterations in tremor presentation in ET patients. Therefore, we characterised
      the dynamics of tremor and cortical activity in ET patients after alprazolam
      intake. METHODS: We recorded hand tremors and contralateral cortical activity in
      four recordings before and after a single dose of alprazolam. We then computed
      the changes in tremors, cortico-muscular coherence, and cortical activity at the
      tremor frequency and in the beta band. RESULTS: Alprazolam significantly
      attenuated tremors (EMG: 76.2 +/- 22.68%), decreased cortical activity in the
      tremor frequency range and increased cortical beta activity in all patients
      (P<0.05). At the same time, the cortico-muscular coherence at the tremor
      frequency became non-significant (P<0.05). We also found a significant
      correlation (r = 0.757, P<0.001) between the reduction in tremor severity and the
      increased ratio of cortical activity in the beta band to the activity observed in
      the tremor frequency range. CONCLUSIONS: This study provides the first
      quantitative analysis of tremor reduction following alprazolam intake. We
      observed that the tremor severity decreased in association with an increased
      ratio of beta to tremor-related cortical activity. We hypothesise that the
      increase in cortical beta activity may act as a blocking mechanism and may dampen
      the pathological oscillatory activity, which in turn attenuates the observed
      tremor.

PMID- 24667765
TI  - Open letter to Xi Jinping, President of the People's Republic of China: China's
      fight against corruption in organ transplantation.

PMID- 24667764
TI  - Telmisartan induces growth inhibition, DNA double-strand breaks and apoptosis in
      human endometrial cancer cells.
AB  - Telmisartan, an angiotensin II receptor type 1 blocker, is often used as an
      antihypertension drug, and it has also been characterized as a peroxisome
      proliferator-activated receptor-gamma (PPARgamma) ligand. The purpose of this
      study was to elucidate the antitumor effects of telmisartan on endometrial cancer
      cells. We treated three endometrial cancer cell lines with various concentrations
      of telmisartan, and we investigated the effects of the telmisartan on the cell
      proliferation, apoptosis, and their related measurements in vitro. We also
      administered telmisartan to nude mice with experimental tumors to determine its
      in vivo effects and toxicity. All three endometrial cancer cell lines were
      sensitive to the growth-inhibitory effect of telmisartan. The induction of
      apoptosis was confirmed in concert with the altered expression of genes and
      proteins related to the apoptosis. We also observed that DNA double-strand breaks
      (DSBs) were induced in HHUA (human endometrial cancer) cells by telmisartan
      treatment. In addition, experiments in nude mice showed that telmisartan
      significantly inhibited human endometrial tumor growth, without toxic side
      effects. Our results suggest that telmisartan might be a new therapeutic option
      for the treatment of endometrial cancers. 

PMID- 24667766
TI  - Positive feedback regulation of proliferation in vascular smooth muscle cells
      stimulated by lipopolysaccharide is mediated through the TLR 4/Rac1/Akt pathway.
AB  - Toll-like receptor 4 (TLR4) are important in inflammation and regulating vascular
      smooth muscle cells (VSMCs) proliferation, which are related to atherosclerosis
      and restenosis. We have investigated the mechanisms involved in
      Lipopolysaccharide (LPS)-induced proliferation of VSMCs. Stimulation of rat
      aortic VSMCs with LPS significantly increases the proliferation of VSMCs. This
      effect is regulated by Rac1 (Ras-related C3 botulinum toxin substrate l), which
      mediates the activation of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling
      pathways. Inhibition of Rac1 activity by NSC23766 is associated with inhibition
      of Akt activity. Treatment with NSC23766 or LY294002 significantly decreases LPS
      induced TLR4 protein and mRNA expression. The data show that positive feedback
      regulation of proliferation in VSMCs is mediated through the TLR4/Rac1/Akt
      pathway. 

PMID- 24667768
TI  - A ruthenium-grafted triazine functionalized mesoporous polymer: a highly
      efficient and multifunctional catalyst for transfer hydrogenation and the Suzuki
      Miyaura cross-coupling reactions.
AB  - A new ruthenium-grafted mesoporous organic polymer Ru-MPTAT-1 has been
      synthesized via simple and facile in situ radical polymerization of 2,4,6
      triallyloxy-1,3,5-triazine (TAT) in aqueous medium in the presence of an anionic
      surfactant (sodium dodecyl sulfate) as a template, followed by grafting of Ru(II)
      onto its surface. Ru-MPTAT-1 has been characterized by elemental analysis, powder
      XRD, HRTEM, FT-IR, UV-vis DRS, TG-DTA, FESEM and XPS characterization tools. The
      Ru-MPTAT-1 material showed very good catalytic activity in the Suzuki-Miyaura
      cross-coupling reaction for aryl halides and transfer hydrogenation reaction for
      a series of carbonyl compounds. The catalyst is easily recoverable from the
      reaction mixture and can be reused several times without appreciable loss of
      catalytic activity in the above reactions. Highly dispersed and strongly bound
      Ru(II) sites at the mesoporous polymer surface could be responsible for the
      observed high activity of the Ru-MPTAT-1 catalyst in these reactions.

PMID- 24667767
TI  - Neuro-intensive treatment targeting intracranial hypertension improves outcome in
      severe bacterial meningitis: an intervention-control study.
AB  - OBJECTIVE: To evaluate the efficacy of early intracranial pressure (ICP)-targeted
      treatment, compared to standard intensive care, in adults with community acquired
      acute bacterial meningitis (ABM) and severely impaired consciousness. DESIGN: A
      prospectively designed intervention-control comparison study of adult cases from
      September 2004 to January 2012. PATIENTS: Included patients were confirmed ABM
      cases, aged 16-75 years, with severely impaired mental status on admission. Fifty
      two patients, given ICP-targeted treatment at the neuro-intensive care unit, and
      53 control cases, treated with conventional intensive care, were included. All
      the patients received intensive care with mechanical ventilation, sedation,
      antibiotics and corticosteroids according to current guidelines. Additional ICP
      treatment in the intervention group included cerebrospinal fluid drainage using
      external ventricular catheters (n = 48), osmotherapy (n = 21), hyperventilation
      (n = 13), external cooling (n = 9), gram-doses of methylprednisolone (n = 3) and
      deep barbiturate sedation (n = 2) aiming at ICP <20 mmHg and a cerebral perfusion
      pressure of >50 mmHg. MEASUREMENTS: The primary endpoint was mortality at two
      months and secondary endpoint was Glasgow outcome score and hearing ability at
      follow-up at 2-6 months. OUTCOMES: The mortality was significantly lower in the
      intervention group compared to controls, 5/52 (10%) versus 16/53 (30%; relative
      risk reduction 68%; p<0.05). Furthermore, only 17 patients (32%) in the control
      group fully recovered compared to 28 (54%) in the intervention group (relative
      risk reduction 40%; p<0.05). CONCLUSIONS: Early neuro-intensive care using ICP
      targeted therapy, mainly cerebrospinal fluid drainage, reduces mortality and
      improves the overall outcome in adult patients with ABM and severely impaired
      mental status on admission.

PMID- 24667769
TI  - Characterization of the growth dynamics and biofilm formation of Staphylococcus
      epidermidis strains isolated from contaminated platelet units.
AB  - Bacterial contamination of platelet concentrates (PCs) poses the highest
      transfusion-associated infectious risk, with Staphylococcus epidermidis being a
      predominant contaminant. Herein, the growth dynamics of 20 S. epidermidis strains
      in PCs and regular media were characterized. Strains were categorized as fast
      (short lag phase) or slow (long lag phase) growers in PCs. All strains were
      evaluated for the presence of the biofilm-associated icaAD genes by PCR, their
      capability to produce extracellular polysaccharide (slime) on Congo red agar
      plates and their ability to form surface-attached aggregates (biofilms) in
      glucose-supplemented trypticase soy broth (TSBg) using a crystal violet staining
      assay. A subset of four strains (two slow growers and two fast growers) was
      further examined for the ability for biofilm formation in PCs. Two of these
      strains carried the icAD genes, formed slime and produced biofilms in TSBg and
      PCs, while the other two strains, which did not carry icaAD, did not produce
      slime or form biofilms in TSBg. Although the two ica-negative slime-negative
      strains did not form biofilms in media, they displayed a biofilm-positive
      phenotype in PCs. Although all four strains formed biofilms in PCs, the two slow
      growers formed significantly more biofilms than the fast growers. Furthermore,
      growth experiments of the two ica-positive strains in plasma-conditioned platelet
      bags containing TSBg revealed that a slow grower isolate was more likely to
      escape culture-based screening than a fast grower strain. Therefore, this study
      provides novel evidence that links S. epidermidis biofilm formation with slow
      growth in PCs and suggests that slow-growing biofilm-positive S. epidermidis
      would be more likely to be missed with automate culture.

PMID- 24667770
TI  - Species distribution and antifungal susceptibility profile of Candida isolates
      from bloodstream infections in Lima, Peru.
AB  - Yeast identification and in vitro susceptibility testing provide helpful
      information for appropriate administration of antifungal treatments; however, few
      reports from the Latin American region have been published. The aim of this study
      was to identify the species present in isolates from bloodstream infections
      diagnosed in nine hospitals in Lima, Peru and to determine their in vitro
      susceptibility to four antifungal drugs. We tested and identified 153 isolates
      collected between October 2009 and August 2011 using standard methods. PCR and
      PCR-RFLP assays were performed to distinguish Candida albicans from Candida
      dubliniensis and to identify species of the Candida parapsilosis and Candida
      glabrata complexes. Antifungal susceptibility testing for fluconazole,
      anidulafungin and voriconazole was performed using the CSLI M27-A3 method, and
      amphotericin B susceptibility was determined using the Etest method. The most
      frequently isolated species were: C. albicans (61; 39.9 %), C. parapsilosis (43;
      28.1 %), C. tropicalis (36; 23.5%) and C. glabrata (8; 5.2 %). The overall
      susceptibility rates were 98.0 %, 98.7 %, 98.0 % and 97.4 % for amphotericin B,
      fluconazole, voriconazole and anidulafungin, respectively. No isolate was
      resistant to more than one drug. These results showed that the rate of resistance
      to four antifungal drugs was low among Candida bloodstream isolates in Lima,
      Peru.

PMID- 24667771
TI  - Failure of Tooth Formation Mediated by miR-135a Overexpression via BMP Signaling.
AB  - MicroRNAs (miRNAs) are known to regulate a variety of gene functions in many
      tissues and organs, but their expression and function in tooth development are
      not well-understood. A specific miRNA, miR-135a, was determined to be highly
      expressed at the bud stage. Interestingly, after the cap stage, miR-135a was
      expressed in the epithelium and mesenchyme but not in the inner enamel
      epithelium. To identify the relationship between miR-135a and its putative target
      genes, Bmpr-Ia and Bmpr-Ib, in early tooth development, miR-135a was ectopically
      overexpressed with a lentivirus. This overexpression resulted in the repression
      of Bmpr-Ia and Bmpr-Ib. Furthermore, miR-135a inhibited both Bmpr-Ia and Bmpr-Ib
      transcription. BMP2 proteins were expressed ectopically in tooth germs during the
      cap stage to determine the relationship between miR-135a and BMP signaling in
      early tooth development. When miR-135a was ectopically expressed, no tooth
      formation was observed after 4 wk of incubation in the kidney capsule. This study
      suggested that Bmp signaling, specifically Bmpr-Ia and Bmpr-Ib, regulates tooth
      formation via miR-135a. 

PMID- 24667772
TI  - Parainfectious optic neuritis: manifestations in children vs adults.
AB  - BACKGROUND: Parainfectious optic neuritis may appear at any age. The aim of our
      report was to compare the clinical manifestations and outcomes of this form of
      optic neuritis between children and adults. METHODS: The study sample consisted
      of all patients diagnosed with parainfectious optic neuritis evaluated by 2 neuro
      ophthalmology services between 2005 and 2012. Data were collected retrospectively
      from the medical files. Findings were compared between patients aged 0-18 years
      and 19 years or older. RESULTS: Ten children (50% female) and 8 adults (50%
      female) met the study criteria. Mean duration of follow-up was 29.4 months
      (range, 2-72 months) in the pediatric group and 14.2 months (range, 5-80 months)
      in the adult group. Respective rates of bilateral disease were 50% and 38%, and
      all patients had optic disc swelling. The associated pathogen was identified in
      60% of the pediatric group, mainly Mycoplasma pneumoniae, and 75% of the adult
      group, in which no microorganism predominated. The interval from the febrile
      illness to symptom onset was 6 days (range, 1-14 days) in the pediatric group and
      19.5 days (range, 14-30 days) in the adult group. Acute disseminated
      encephalomyelitis (ADEM) was diagnosed in 40% (4/10) of the children and none of
      the adults. Final visual outcome was 20/30 or better in all patients. There was a
      higher frequency of bilateral disease in prepubescent vs postpubescent children.
      CONCLUSIONS: Parainfectious optic neuritis is associated with a favorable visual
      prognosis regardless of age. Children tend to manifest visual symptoms sooner
      after the antecedent infectious illness and more often bilaterally and in
      conjunction with ADEM. The causative agent is isolated less frequently in
      children compared with adults.

PMID- 24667773
TI  - Third nerve palsy as the initial manifestation of giant cell arteritis.
AB  - OBJECTIVE: Giant cell arteritis (GCA) is rarely reported as a cause of third
      nerve palsy. We describe the presentation and course of patients with third nerve
      palsy as the sole initial ocular manifestation of GCA. METHODS: Retrospective
      chart review of patients with third nerve palsy as the presenting sign of GCA.
      Symptoms, signs, and inflammatory marker levels at presentation and on follow-up
      were analyzed. All patients had imaging of the brain and circle of Willis, to
      exclude a compressive or inflammatory lesion, and had a temporal artery biopsy
      showing granulomatous arteritis. RESULTS: Four patients (aged 63-82) were
      identified and included. One patient had a complete third nerve palsy with pupil
      involvement, whereas the other 3 had third nerve palsies without pupil
      involvement. Three patients had ipsilateral periorbital/brow pain, and the other
      patient had temporal headache. Two patients reported no systemic symptoms of GCA
      but had elevated inflammatory markers. One patient had normal inflammatory
      markers but reported systemic symptoms of GCA. All patients had rapid improvement
      in symptoms and signs after high-dose oral prednisone was started with all
      showing complete recovery within weeks. CONCLUSIONS: GCA can rarely present with
      acute painful third nerve palsy, mimicking the presentation of a microvascular
      cause. The third nerve palsy often improves rapidly after steroid treatment is
      started. The presence of GCA symptoms or elevated inflammatory markers in a
      patient older than 50 years with an acute third nerve palsy should prompt
      initiation of high-dose steroid treatment and temporal artery biopsy.

PMID- 24667774
TI  - Downbeat nystagmus elicited by eyelid closure.
AB  - We describe a patient with downbeat nystagmus (DBN) evoked only by eye closure.
      Brain and spinal cord magnetic resonance imaging revealed a T2 paramedian lesion
      in the left lower basis pontis and other white matter lesions consistent with
      multiple sclerosis. One potential mechanism for DBN in this case involves
      transverse ephaptic spread of excitation from areas that subserve coordinated lid
      closure to the decussating ventral tegmental tract.

PMID- 24667775
TI  - The invA gene of Brucella melitensis is involved in intracellular invasion and is
      required to establish infection in a mouse model.
AB  - Some of the mechanisms underlying the invasion and intracellular survival of B.
      melitensis are still unknown, including the role of a subfamily of NUDIX enzymes,
      which have been described in other bacterial species as invasins and are present
      in Brucella spp. We have generated a mutation in the coding gene of one of these
      proteins, the invA gene (BMEI0215) of B. melitensis strain 133, to understand its
      role in virulence. HeLa cell invasion results showed that mutant strain survival
      was decreased 5-fold compared with that of the parental strain at 2 h pi
      (P<0.001). In a goat macrophage infection assay, mutant strain replication was 8
      fold less than in the parental strain at 24 h pi (P<0.001); yet, at 48 h pi, no
      significant differences in intracellular replication were observed. Additionally,
      colocalization of the invA mutant with calregulin was significantly lower at 24 h
      pi compared with that of the parental strain. Furthermore, the mutant strain
      exhibited a low level of colocalization with cathepsin D, which was similar to
      the parental strain colocalization at 24 h pi. In vivo infection results
      demonstrated that spleen colonization was significantly lower with the mutant
      than with the parental strain. The immune response, measured in terms of antibody
      switching and IFN-gamma transcription, was similar for Rev1 and infection with
      the mutant, although it was lower than the immune response elicited by the
      parental strain. Consequently, these results indicate that the invA gene is
      important during invasion but not for intracellular replication. Additionally,
      mutation of the invA gene results in in vivo attenuation. 

PMID- 24667776
TI  - Metformin and berberine prevent olanzapine-induced weight gain in rats.
AB  - Olanzapine is a first line medication for the treatment of schizophrenia, but it
      is also one of the atypical antipsychotics carrying the highest risk of weight
      gain. Metformin was reported to produce significant attenuation of antipsychotic
      induced weight gain in patients, while the study of preventing olanzapine-induced
      weight gain in an animal model is absent. Berberine, an herbal alkaloid, was
      shown in our previous studies to prevent fat accumulation in vitro and in vivo.
      Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we
      demonstrated that two weeks of metformin or berberine treatment significantly
      prevented the olanzapine-induced weight gain and white fat accumulation. Neither
      metformin nor berberine treatment demonstrated a significant inhibition of
      olanzapine-increased food intake. But interestingly, a significant loss of brown
      adipose tissue caused by olanzapine treatment was prevented by the addition of
      metformin or berberine. Our gene expression analysis also demonstrated that the
      weight gain prevention efficacy of metformin or berberine treatment was
      associated with changes in the expression of multiple key genes controlling
      energy expenditure. This study not only demonstrates a significant preventive
      efficacy of metformin and berberine treatment on olanzapine-induced weight gain
      in rats, but also suggests a potential mechanism of action for preventing
      olanzapine-reduced energy expenditure. 

PMID- 24667777
TI  - Redistribution of ionotropic glutamate receptors detected by laser
      microdissection of the rat dentate gyrus 48 h following LTP induction in vivo.
AB  - The persistence and input specificity of long-term potentiation (LTP) make it
      attractive as a mechanism of information storage. In its initial phase, both in
      vivo and in vitro studies have shown that LTP is associated with increased
      membrane localization of AMPA receptor subunits, but the molecular basis of LTP
      maintenance over the long-term is still unclear. We have previously shown that
      expression of AMPA and NMDA receptor subunits is elevated in whole homogenates
      prepared from dentate gyrus 48 h after LTP induction in vivo. In the present
      study, we utilized laser microdissection (LMD) techniques to determine whether
      AMPA and NMDA receptor upregulation occurs specifically in the stimulated regions
      of the dentate gyrus dendritic arbor. Receptor proteins GluN1, GluA1 and GluA2,
      as well as postsynaptic density protein of 95 kDa and tubulin were detected by
      Western blot analysis in microdissected samples. Gradients of expression were
      observed for GluN1 and GluA2, decreasing from the inner to the outer zones of the
      molecular layer, and were independent of LTP. When induced at medial perforant
      path synapses, LTP was associated with an apparent specific redistribution of
      GluA1 and GluN1 to the middle molecular layer that contains these synapses. These
      data indicate that glutamate receptor proteins are delivered specifically to
      dendritic regions possessing LTP-expressing synapses, and that these changes are
      preserved for at least 48 h. 

PMID- 24667778
TI  - Selective visual detection of trace trinitrotoluene residues based on dual-color
      fluorescence of graphene oxide-nanocrystals hybrid probe.
AB  - Herein, for the detection of highly explosive 2,4,6-trinitrotoluene (TNT)
      instantly and on-site, a fluorescence ratiometric probe using a dual-emission
      nanohybrid has been developed. The nanohybrid comprises blue-colored fluorescent
      graphene oxide (FGO) being conjugated with red-emitting manganese-doped ZnS
      nanocrystals (ZnS:Mn NCs), the latter being functionalized with
      hexamethylenediamine. The blue fluorescence of FGO is insensitive to TNT and is
      used as an internal reference, whereas the red fluorescence of ZnS:Mn NCs can be
      selectively quenched by TNT through electron transfer, resulting in a unique red
      purple-blue color response as the amount of TNT is increased. Thus, the probe
      could be used for the quantitative measurement of TNT based on the fluorescence
      ratiometric method. We demonstrated that the nanohybrid probe exhibited high
      visual detection sensitivity and reliability in comparison with single-color
      fluorescence quenching probes. A fluorescence test paper was prepared using the
      nanohybrid probe and was demonstrated to detect TNT residues directly on various
      surfaces including rubber, a person's fingers and manila envelopes with a visual
      detection limit as low as 5.68 ng mm(-2), showing its promising application for
      security screening. 

PMID- 24667779
TI  - Functional characterization of BRCA1 gene variants by mini-gene splicing assay.
AB  - Mutational screening of the breast cancer susceptibility gene BRCA1 leads to the
      identification of numerous pathogenic variants such as frameshift and nonsense
      variants, as well as large genomic rearrangements. The screening moreover
      identifies a large number of variants, for example, missense, silent, and intron
      variants, which are classified as variants of unknown clinical significance owing
      to the lack of causal evidence. Variants of unknown clinical significance can
      potentially have an impact on splicing and therefore functional examinations are
      warranted to classify whether these variants are pathogenic or benign. Here we
      validate a mini-gene splicing assay by comparing the results of 24 variants with
      previously published data from RT-PCR analysis on RNA from blood
      samples/lymphoblastoid cell lines. The analysis showed an overall concordance of
      100%. In addition, we investigated 13 BRCA1 variants of unknown clinical
      significance or putative variants affecting splicing by in silico analysis and
      mini-gene splicing assay. Both the in silico analysis and mini-gene splicing
      assay classified six BRCA1 variants as pathogenic (c.80+1G>A, c.132C>T (p.=),
      c.213-1G>A, c.670+1delG, c.4185+1G>A, and c.5075-1G>C), whereas six BRCA1
      variants were classified as neutral (c.-19-22_-19-21dupAT, c.302-15C>G,
      c.547+14delG, c.4676-20A>G, c.4987-21G>T, and c.5278-14C>G) and one BRCA1 variant
      remained unclassified (c.670+16G>A). In conclusion, our study emphasizes that in
      silico analysis and mini-gene splicing assays are important for the
      classification of variants, especially if no RNA is available from the patient.
      This knowledge is crucial for proper genetic counseling of patients and their
      family members. 

PMID- 24667780
TI  - Haplotype differences for copy number variants in the 22q11.23 region among human
      populations: a pigmentation-based model for selective pressure.
AB  - Two gene clusters are tightly linked in a narrow region of chromosome 22q11.23:
      the macrophage migration inhibitory factor (MIF) gene family and the glutathione
      S-transferase theta class. Within 120 kb in this region, two 30-kb deletions
      reach high frequencies in human populations. This gives rise to four haplotypic
      arrangements, which modulate the number of genes in both families. The variable
      patterns of linkage disequilibrium (LD) between these copy number variants (CNVs)
      in diverse human populations remain poorly understood. We analyzed 2469
      individuals belonging to 27 human populations with different ethnic origins. Then
      we correlated the genetic variability of 22q11.23 CNVs with environmental
      variables. We confirmed an increasing strength of LD from Africa to Asia and to
      Europe. Further, we highlighted strongly significant correlations between the
      frequency of one of the haplotypes and pigmentation-related variables: skin color
      (R(2)=0.675, P<0.001), distance from the equator (R(2)=0.454, P<0.001), UVA
      radiation (R(2)=0.439, P<0.001), and UVB radiation (R(2)=0.313, P=0.002). The
      fact that all MIF-related genes are retained on this haplotype and the evidences
      gleaned from experimental systems seem to agree with the role of MIF-related
      genes in melanogenesis. As such, we propose a model that explains the geographic
      and ethnic distribution of 22q11.23 CNVs among human populations, assuming that
      MIF-related gene dosage could be associated with adaptation to low UV radiation. 

PMID- 24667781
TI  - Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts.
AB  - Polyglutamine (polyQ) disorders are inherited neurodegenerative conditions
      defined by a common pathogenic CAG repeat expansion leading to a toxic gain-of
      function of the mutant protein. Consequences of this toxicity include activation
      of heat-shock proteins (HSPs), impairment of the ubiquitin-proteasome pathway and
      transcriptional dysregulation. Several studies in animal models have shown that
      reducing levels of toxic protein using small RNAs would be an ideal therapeutic
      approach for such disorders, including spinocerebellar ataxia-7 (SCA7). However,
      testing such RNA interference (RNAi) effectors in genetically appropriate patient
      cell lines with a disease-relevant phenotype has yet to be explored. Here, we
      have used primary adult dermal fibroblasts from SCA7 patients and controls to
      assess the endogenous allele-specific silencing of ataxin-7 by two distinct
      siRNAs. We further identified altered expression of two disease-relevant
      transcripts in SCA7 patient cells: a twofold increase in levels of the HSP DNAJA1
      and a twofold decrease in levels of the de-ubiquitinating enzyme, UCHL1. After
      siRNA treatment, the expression of both genes was restored towards normal levels.
      To our knowledge, this is the first time that allele-specific silencing of mutant
      ataxin-7, targeting a common SNP, has been demonstrated in patient cells. These
      findings highlight the advantage of an allele-specific RNAi-based therapeutic
      approach, and indicate the value of primary patient-derived cells as useful
      models for mechanistic studies and for measuring efficacy of RNAi effectors on a
      patient-to-patient basis in the polyQ diseases. 

PMID- 24667782
TI  - Analysis of the whole mitochondrial genome: translation of the Ion Torrent
      Personal Genome Machine system to the diagnostic bench?
AB  - Next-generation sequencing (NGS), an innovative sequencing technology that
      enables the successful analysis of numerous gene sequences in a massive parallel
      sequencing approach, has revolutionized the field of molecular biology. Although
      NGS was introduced in a rather recent past, the technology has already
      demonstrated its potential and effectiveness in many research projects, and is
      now on the verge of being introduced into the diagnostic setting of routine
      laboratories to delineate the molecular basis of genetic disease in undiagnosed
      patient samples. We tested a benchtop device on retrospective genomic DNA (gDNA)
      samples of controls and patients with a clinical suspicion of a mitochondrial DNA
      disorder. This Ion Torrent Personal Genome Machine platform is a high-throughput
      sequencer with a fast turnaround time and reasonable running costs. We challenged
      the chemistry and technology with the analysis and processing of a mutational
      spectrum composed of samples with single-nucleotide substitutions, indels
      (insertions and deletions) and large single or multiple deletions, occasionally
      in heteroplasmy. The output data were compared with previously obtained
      conventional dideoxy sequencing results and the mitochondrial revised Cambridge
      Reference Sequence (rCRS). We were able to identify the majority of all
      nucleotide alterations, but three false-negative results were also encountered in
      the data set. At the same time, the poor performance of the PGM instrument in
      regions associated with homopolymeric stretches generated many false-positive
      miscalls demanding additional manual curation of the data. 

PMID- 24667783
TI  - Genetic analysis, in silico prediction, and family segregation in long QT
      syndrome.
AB  - The heritable cardiovascular disorder long QT syndrome (LQTS), characterized by
      prolongation of the QT interval on electrocardiogram, carries a high risk of
      sudden cardiac death. We sought to add new data to the existing knowledge of
      genetic mutations contributing to LQTS to both expand our understanding of its
      genetic basis and assess the value of genetic testing in clinical decision
      making. Direct sequencing of the five major contributing genes, KCNQ1, KCNH2,
      SCN5A, KCNE1, and KCNE2, was performed in a cohort of 115 non-related LQTS
      patients. Pathogenicity of the variants was analyzed using family segregation,
      allele frequency from public databases, conservation analysis, and Condel and
      Provean in silico predictors. Phenotype-genotype correlations were analyzed
      statistically. Sequencing identified 36 previously described and 18 novel
      mutations. In 51.3% of the index cases, mutations were found, mostly in KCNQ1,
      KCNH2, and SCN5A; 5.2% of cases had multiple mutations. Pathogenicity analysis
      revealed 39 mutations as likely pathogenic, 12 as VUS, and 3 as non-pathogenic.
      Clinical analysis revealed that 75.6% of patients with QTc>=500 ms were
      genetically confirmed. Our results support the use of genetic testing of KCNQ1,
      KCNH2, and SCN5A as part of the diagnosis of LQTS and to help identify relatives
      at risk of SCD. Further, the genetic tools appear more valuable as disease
      severity increases. However, the identification of genetic variations in the
      clinical investigation of single patients using bioinformatic tools can produce
      erroneous conclusions regarding pathogenicity. Therefore segregation studies are
      key to determining causality. 

PMID- 24667784
TI  - Brugada syndrome risk loci seem protective against atrial fibrillation.
AB  - Several studies have shown an overlap between genes involved in the
      pathophysiological mechanisms of atrial fibrillation (AF) and Brugada Syndrome
      (BrS). We investigated whether three single-nucleotide polymorphisms (SNPs)
      (rs11708996; G>C located intronic to SCN5A, rs10428132; T>G located in SCN10A,
      and rs9388451; T>C located downstream to HEY2) at loci associated with BrS in a
      recent genome-wide association study (GWAS) also were associated with AF. A total
      of 657 patients diagnosed with AF and a control group comprising 741 individuals
      free of AF were included. The three SNPs were genotyped using TaqMan assays. The
      frequencies of risk alleles in the AF population and the control population were
      compared in two-by-two models. One variant, rs10428132 at SCN10A, was associated
      with a statistically significant decreased risk of AF (odds ratio (OR)=0.77,
      P=0.001). A meta-analysis was performed by enriching the control population with
      allele frequencies from controls in the recently published BrS GWAS (2230
      alleles). In this meta-analysis, both rs10428132 at SCN10A (OR=0.73, P=5.7 * 10(
      6)) and rs11708996 at SCN5A (OR=0.80, P=0.02) showed a statistically significant
      decreased risk of AF. When assessing the additive effect of the three loci, we
      found that the risk of AF decreased in a dose-responsive manner with increasing
      numbers of risk alleles (OR=0.50, P=0.001 for individuals carrying >=4 risk
      alleles vs <=1 allele). In conclusion, the prevalence of three risk alleles
      previously associated with BrS was lower in AF patients than in patients free of
      AF, suggesting a protective role of these loci in developing AF. 

PMID- 24667785
TI  - Test of rare variant association based on affected sib-pairs.
AB  - With the development of sequencing techniques, there is increasing interest to
      detect associations between rare variants and complex traits. Quite a few
      statistical methods to detect associations between rare variants and complex
      traits have been developed for unrelated individuals. Statistical methods for
      detecting rare variant associations under family-based designs have not received
      as much attention as methods for unrelated individuals. Recent studies show that
      rare disease variants will be enriched in family data and thus family-based
      designs may improve power to detect rare variant associations. In this article,
      we propose a novel test to test association between the optimally weighted
      combination of variants and trait of interests for affected sib-pairs. The
      optimal weights are analytically derived and can be calculated from sampled
      genotypes and phenotypes. Based on the optimal weights, the proposed method is
      robust to the directions of the effects of causal variants and is less affected
      by neutral variants than existing methods are. Our simulation results show that,
      in all the cases, the proposed method is substantially more powerful than
      existing methods based on unrelated individuals and existing methods based on
      affected sib-pairs. 

PMID- 24667786
TI  - The phylogenetic and geographic structure of Y-chromosome haplogroup R1a.
AB  - R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its
      substructure within Europe and Asia has remained poorly characterized. Using a
      panel of 16 244 male subjects from 126 populations sampled across Eurasia, we
      identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular
      phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and
      five R1b individuals suggests a divergence time of ~25,000 (95% CI: 21,300
      29,000) years ago and a coalescence time within R1a-M417 of ~5800 (95% CI: 4800
      6800) years. The spatial frequency distributions of R1a sub-haplogroups
      conclusively indicate two major groups, one found primarily in Europe and the
      other confined to Central and South Asia. Beyond the major European versus Asian
      dichotomy, we describe several younger sub-haplogroups. Based on spatial
      distributions and diversity patterns within the R1a-M420 clade, particularly rare
      basal branches detected primarily within Iran and eastern Turkey, we conclude
      that the initial episodes of haplogroup R1a diversification likely occurred in
      the vicinity of present-day Iran.

PMID- 24667787
TI  - Characterization of the transcriptional machinery bound across the widely
      presumed type 2 diabetes causal variant, rs7903146, within TCF7L2.
AB  - Resolving the underlying functional mechanism to a given genetic association has
      proven extremely challenging. However, the strongest associated type 2 diabetes
      (T2D) locus reported to date, TCF7L2, presents an opportunity for translational
      analyses, as many studies in multiple ethnicities strongly point to SNP rs7903146
      in intron 3 as being the causal variant within this gene. We carried out oligo
      pull-down combined with mass spectrophotometry (MS) to elucidate the specific
      transcriptional machinery across this SNP using protein extracts from HCT116
      cells. We observed that poly (ADP-ribose) polymerase 1 (PARP-1) is by far the
      most abundant binding factor. Pursuing the possibility of a feedback mechanism,
      we observed that PARP-1, along with the next most abundant binding proteins, DNA
      topoisomerase I and ATP-dependent RNA helicase A, dimerize with the TCF7L2
      protein and with each other. We uncovered further evidence of a feedback
      mechanism using a luciferase reporter approach, including observing expression
      differences between alleles for rs7903146. We also found that there was an
      allelic difference in the MS results for proteins with less abundant binding,
      namely X-ray repair cross-complementing 5 and RPA/p70. Our results point to a
      protein complex binding across rs7903146 within TCF7L2 and suggests a possible
      mechanism by which this locus confers its T2D risk. 

PMID- 24667788
TI  - Analyses of the mitochondrial mutations in the Chinese patients with sporadic
      Creutzfeldt-Jakob disease.
AB  - Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial
      dysfunction can cause a variety of chronic diseases in central nervous system
      (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt-Jakob disease
      (sCJD) has still been unknown. In this study, we comparatively analyzed complete
      mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and
      PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in
      control by haplogroup and allele frequencies. We classified the mtDNAs into 40
      sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups.
      Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The
      analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA
      CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six
      CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one
      in control (P<0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu)
      were detected in sCJD. The frequencies of two synonymous amino-acid changes,
      m.11467A>G, p.(=) in NADH dehydrogenase subunit 4 (ND4) and m.12372G>A, p.(=) in
      NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of
      controls. Our study, for the first time, screened the variations of mtDNA of
      Chinese sCJD patients and identified some potential disease-related mutations for
      further investigations. 

PMID- 24667789
TI  - Unravelling the distinct strains of Tharu ancestry.
AB  - The northern region of the Indian subcontinent is a vast landscape interlaced by
      diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great
      number of ethnic groups are found there, displaying a multitude of languages and
      cultures. The Tharu is one of the largest and most linguistically diverse of such
      groups, scattered across the Tarai region of Nepal and bordering Indian states.
      Their origins are uncertain. Hypotheses have been advanced postulating shared
      ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as
      aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan
      languages, but have traditionally been described by ethnographers as representing
      East Asian phenotype. Their ancestry and intra-population diversity has
      previously been tested only for haploid (mitochondrial DNA and Y-chromosome)
      markers in a small portion of the population. This study presents the first
      systematic genetic survey of the Tharu from both Nepal and two Indian states of
      Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We
      show that the Tharu have dual genetic ancestry as up to one-half of their gene
      pool is of East Asian origin. Within the South Asian proportion of the Tharu
      genetic ancestry, we see vestiges of their common origin in the north of the
      South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43. 

PMID- 24667790
TI  - Y-chromosome E haplogroups: their distribution and implication to the origin of
      Afro-Asiatic languages and pastoralism.
AB  - Archeological and paleontological evidences point to East Africa as the likely
      area of early evolution of modern humans. Genetic studies also indicate that
      populations from the region often contain, but not exclusively, representatives
      of the more basal clades of mitochondrial and Y-chromosome phylogenies. Most Y
      chromosome haplogroup diversity in Africa, however, is present within
      macrohaplogroup E that seem to have appeared 21 000-32 000 YBP somewhere between
      the Red Sea and Lake Chad. The combined analysis of 17 bi-allelic markers in 1214
      Y chromosomes together with cultural background of 49 populations displayed in
      various metrics: network, multidimensional scaling, principal component analysis
      and neighbor-joining plots, indicate a major contribution of East African
      populations to the foundation of the macrohaplogroup, suggesting a
      diversification that predates the appearance of some cultural traits and the
      subsequent expansion that is more associated with the cultural and linguistic
      diversity witnessed today. The proto-Afro-Asiatic group carrying the E-P2
      mutation may have appeared at this point in time and subsequently gave rise to
      the different major population groups including current speakers of the Afro
      Asiatic languages and pastoralist populations. 

PMID- 24667792
TI  - Design of optimally constructed metabolic networks of minimal functionality.
AB  - BACKGROUND: Metabolic engineering aims to design microorganisms that will
      generate a product of interest at high yield. Thus, a variety of in silico
      modeling strategies has been applied successfully, including the concepts of
      elementary flux modes (EFMs) and constrained minimal cut sets (cMCSs). The EFMs
      (minimal, steady state pathways through the system) can be calculated given a
      metabolic model. cMCSs are sets of reaction deletions in such a network that will
      allow desired pathways to survive and disable undesired ones (e.g., those with
      low product secretion or low growth rates). Grouping the modes into desired and
      undesired categories had to be done manually until now. RESULTS: Although the
      optimal solution for a given set of pathways will always be found with the
      currently available tools, manual selection may lead to a sub-optimal solution
      with respect to a metabolic engineering target. A small change in the selection
      of modes can reduce the number of necessary deletions while only slightly
      reducing production. Based on our recently introduced formulation of cut set
      calculations using binary linear programming, we suggest an algorithm that does
      not require manual selection of the desired pathways. CONCLUSIONS: We
      demonstrated the principle of our algorithm with the help of a small toy network
      and applied it to a model of E. coli using different design objectives.
      Furthermore we validated our method by reproducing previously obtained results
      without requiring manual grouping of modes.

PMID- 24667791
TI  - Lack of association between intact/deletion polymorphisms of the APOBEC3B gene
      and HIV-1 risk.
AB  - OBJECTIVE: The human APOBEC3 family of proteins potently restricts HIV-1
      replication APOBEC3B, one of the family genes, is frequently deleted in human
      populations. Two previous studies reached inconsistent conclusions regarding the
      effects of APOBEC3B loss on HIV-1 acquisition and pathogenesis. Therefore, it was
      necessary to verify the effects of APOBEC3B on HIV-1 infection in vivo. METHODS:
      Intact (I) and deletion (D) polymorphisms of APOBEC3B were analyzed using PCR.
      The syphilis, HBV and HCV infection rates, as well as CD4(+) T cell counts and
      viral loads were compared among three APOBEC3B genotype groups (I/I, D/I, and
      D/D). HIV-1 replication kinetics was assayed in vitro using primary cells derived
      from PBMCs. RESULTS: A total of 248 HIV-1-infected Japanese men who have sex with
      men (MSM) patients and 207 uninfected Japanese MSM were enrolled in this study.
      The genotype analysis revealed no significant differences between the APOBEC3B
      genotype ratios of the infected and the uninfected cohorts (p = 0.66). In
      addition, HIV-1 disease progression parameters were not associated with the
      APOBEC3B genotype. Furthermore, the PBMCs from D/D and I/I subjects exhibited
      comparable HIV-1 susceptibility. CONCLUSION: Our analysis of a population-based
      matched cohort suggests that the antiviral mechanism of APOBEC3B plays only a
      negligible role in eliminating HIV-1 in vivo.

PMID- 24667793
TI  - Carbon nanotube chemiresistor for wireless pH sensing.
AB  - The ability to accurately measure real-time pH fluctuations in-vivo could be
      highly advantageous. Early detection and potential prevention of bacteria
      colonization of surgical implants can be accomplished by monitoring associated
      acidosis. However, conventional glass membrane or ion-selective field-effect
      transistor (ISFET) pH sensing technologies both require a reference electrode
      which may suffer from leakage of electrolytes and potential contamination.
      Herein, we describe a solid-state sensor based on oxidized single-walled carbon
      nanotubes (ox-SWNTs) functionalized with the conductive polymer poly(1
      aminoanthracene) (PAA). This device had a Nernstian response over a wide pH range
      (2-12) and retained sensitivity over 120 days. The sensor was also attached to a
      passively-powered radio-frequency identification (RFID) tag which transmits pH
      data through simulated skin. This battery-less, reference electrode free,
      wirelessly transmitting sensor platform shows potential for biomedical
      applications as an implantable sensor, adjacent to surgical implants detecting
      for infection. 

PMID- 24667795
TI  - How can journals respond to threats of libel litigation?

PMID- 24667796
TI  - Exercise programmes for older people with dementia may have an effect on
      cognitive function and activities of daily living, but studies give inconsistent
      results.

PMID- 24667794
TI  - Imported case of acute respiratory tract infection associated with a member of
      species nelson bay orthoreovirus.
AB  - A Japanese man suffered from acute respiratory tract infection after returning to
      Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species
      of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using
      Vero cells, in which syncytium formation was observed. This is the sixth report
      describing a patient with respiratory tract infection caused by an orthoreovirus
      classified to the species of Nelson Bay orthoreovirus. Given the possibility that
      all of the patients were infected in Malaysia and Indonesia, prospective
      surveillance on orthoreovirus infections should be carried out in Southeast Asia.
      Furthermore, contact surveillance study suggests that the risk of human-to-human
      infection of the species of Nelson Bay orthoreovirus would seem to be low. 

PMID- 24667797
TI  - Older people identified by social services to be at risk of abuse have higher
      rates of hospitalisation.

PMID- 24667799
TI  - 11beta-hydroxysteroid dehydrogenase 1 specific inhibitor increased dermal
      collagen content and promotes fibroblast proliferation.
AB  - Glucocorticoids (GCs) are one of the most effective anti-inflammatory drugs for
      treating acute and chronic inflammatory diseases. However, several studies have
      shown that GCs alter collagen metabolism in the skin and induce skin atrophy.
      Cortisol is the endogenous GC that is released in response to various stressors.
      Over the last decade, extraadrenal cortisol production in various tissues has
      been reported. Skin also synthesizes cortisol through a de novo pathway and
      through an activating enzyme. 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1)
      is the enzyme that catalyzes the conversion of hormonally inactive cortisone to
      active cortisol in cells. We previously found that 11beta-HSD1 negatively
      regulates proliferation of keratinocytes. To determine the function of 11beta
      HSD1 in dermal fibroblasts and collagen metabolism, the effect of a selective
      11beta-HSD1 inhibitor was studied in mouse tissues and dermal fibroblasts. The
      expression of 11beta-HSD1 increased with age in mouse skin. Subcutaneous
      injection of a selective 11beta-HSD1 inhibitor increased dermal thickness and
      collagen content in the mouse skin. In vitro, proliferation of dermal fibroblasts
      derived from 11beta-HSD1 null mice (Hsd11b1(-/-) mice) was significantly
      increased compared with fibroblasts from wild-type mice. However, in vivo, dermal
      thickness of Hsd11b1(-/-) mice was not altered in 3-month-old and 1-year-old
      mouse skin compared with wild-type mouse skin. These in vivo findings suggest the
      presence of compensatory mechanisms in Hsd11b1(-/-) mice. Our findings suggest
      that 11beta-HSD1 inhibition may reverse the decreased collagen content observed
      in intrinsically and extrinsically aged skin and in skin atrophy that is induced
      by GC treatment.

PMID- 24667798
TI  - Inhibition of cathepsin B by E-64 induces oxidative stress and apoptosis in
      filarial parasite.
AB  - BACKGROUND: Current available antifilarial drug strategies only eliminate the
      larval stages of filarial parasites. Therefore, there is an urgent need of drugs
      which are macrofilaricidals. Identification of molecular targets crucial for
      survival of parasite is a prerequisite for drug designing. Cathepsin B, a
      cysteine protease family member is known to play crucial role in the normal
      growth, digestion of nutrients, exsheathment of the helminth parasites.
      Therefore, we targeted this enzyme in the filarial parasite using its specific
      inhibitor, E-64. METHODS AND FINDINGS: We have exposed the parasites to E-64 and
      observed their motility and viability at various time intervals. It caused marked
      decrease in the motility and viability of the parasites ultimately leading to
      their death after 8 hours. It is well known that E-64 protects the cell from
      apoptosis, however, it causes apoptotic effect in carcinoma cell lines. To
      understand the mechanism of action of E-64 on parasite survival, we have measured
      levels of different apoptotic markers in the treated parasites. E-64
      significantly reduced the level of ced-9 and activity of tyrosine phosphatases,
      cytochrome c oxidase. It also activated ced-3, homolog of mammalian caspase 3
      suggesting initiation of an apoptotic like event in the filarial parasites.
      Different antioxidant enzymes were also evaluated to further explore the
      mechanism behind the death of the parasites. There was marked decrease in the
      level of GSH and activity of Glutathione reductase and glutathione-s-transferase
      leading to increased generation of reactive oxygen species. This led to the
      induced oxidation of fatty acids and protein which might alter the mitochondrial
      membrane permeability. CONCLUSION: This study suggests that inhibition of
      cathepsin B by E-64 generates oxidative stress followed by mitochondrial mediated
      apoptotic like event in filarial parasites leading to their death. Hence,
      suggesting filarial cathepsin B as a potential chemotherapeutic target for
      lymphatic filariasis.

PMID- 24667800
TI  - Klebsiella pneumoniae oropharyngeal carriage in rural and urban Vietnam and the
      effect of alcohol consumption.
AB  - INTRODUCTION: Community acquired K. pneumoniae pneumonia is still common in Asia
      and is reportedly associated with alcohol use. Oropharyngeal carriage of K.
      pneumoniae could potentially play a role in the pathogenesis of K. pneumoniae
      pneumonia. However, little is known regarding K. pneumoniae oropharyngeal
      carriage rates and risk factors. This population-based cross-sectional study
      explores the association of a variety of demographic and socioeconomic factors,
      as well as alcohol consumption with oropharyngeal carriage of K. pneumoniae in
      Vietnam. METHODS AND FINDINGS: 1029 subjects were selected randomly from age,
      sex, and urban and rural strata. An additional 613 adult men from a rural
      environment were recruited and analyzed separately to determine the effects of
      alcohol consumption. Demographic, socioeconomic, and oropharyngeal carriage data
      was acquired for each subject. The overall carriage rate of K. pneumoniae was
      14.1% (145/1029, 95% CI 12.0%-16.2%). By stepwise logistic regression, K.
      pneumoniae carriage was found to be independently associated with age (OR 1.03,
      95% CI 1.02-1.04), smoking (OR 1.9, 95% CI 1.3-2.9), rural living location (OR
      1.6, 95% CI 1.1-2.4), and level of weekly alcohol consumption (OR 1.7, 95% CI
      1.04-2.8). CONCLUSION: Moderate to heavy weekly alcohol consumption, old age,
      smoking, and living in a rural location are all found to be associated with an
      increased risk of K. pneumoniae carriage in Vietnamese communities. Whether K.
      pneumoniae carriage is a risk factor for pneumonia needs to be elucidated.

PMID- 24667801
TI  - Effect of redox conditions on bacterial community structure in Baltic Sea
      sediments with contrasting phosphorus fluxes.
AB  - Phosphorus release from sediments can exacerbate the effect of eutrophication in
      coastal marine ecosystems. The flux of phosphorus from marine sediments to the
      overlying water is highly dependent on the redox conditions at the sediment-water
      interface. Bacteria are key players in the biological processes that release or
      retain phosphorus in marine sediments. To gain more insight in the role of
      bacteria in phosphorus release from sediments, we assessed the effect of redox
      conditions on the structure of bacterial communities. To do so, we incubated
      surface sediments from four sampling sites in the Baltic Sea under oxic and
      anoxic conditions and analyzed the fingerprints of the bacterial community
      structures in these incubations and the original sediments. This paper describes
      the effects of redox conditions, sampling station, and sample type (DNA, RNA, or
      whole-cell sample) on bacterial community structure in sediments. Redox
      conditions explained only 5% of the variance in community structure, and
      bacterial communities from contrasting redox conditions showed considerable
      overlap. We conclude that benthic bacterial communities cannot be classified as
      being typical for oxic or anoxic conditions based on community structure
      fingerprints. Our results suggest that the overall structure of the benthic
      bacterial community has only a limited impact on benthic phosphate fluxes in the
      Baltic Sea. 

PMID- 24667802
TI  - Rational nanostructuring of surfaces for extraordinary icephobicity.
AB  - Icing of surfaces is commonplace in nature, technology and everyday life,
      bringing with it sometimes catastrophic consequences. A rational methodology for
      designing materials with extraordinary resistance to ice formation and adhesion
      remains however elusive. We show that ultrafine roughnesses can be fabricated, so
      that the ice nucleation-promoting effect of nanopits on surfaces is effectively
      counteracted in the presence of an interfacial quasiliquid layer. The ensuing
      interface confinement strongly suppresses the stable formation of ice nuclei. We
      explain why such nanostructuring leads to the same extremely low, robust
      nucleation temperature of ~-24  degrees C for over three orders of magnitude
      change in RMS size (~0.1 to ~100 nm). Overlaying such roughnesses on pillar
      microtextures harvests the additional benefits of liquid repellency and low ice
      adhesion. When tested at a temperature of -21  degrees C, such surfaces delayed
      the freezing of a sessile supercooled water droplet at the same temperature by a
      remarkable 25 hours. 

PMID- 24667803
TI  - Fixation of unstable type II clavicle fractures with distal clavicle plate and
      suture button.
AB  - This article reports on a technique to treat unstable type II distal clavicle
      fractures using fracture-specific plates and coracoclavicular augmentation with a
      suture button. Six patients with clinically unstable type II distal clavicle
      fractures underwent treatment using the above technique. All fractures
      demonstrated radiographic union at 9.6 (8.4-11.6) weeks with a mean follow-up of
      15.6 (12.4-22.3) months. American Shoulder and Elbow Surgeons, Penn Shoulder
      Score, and Single Assessment Numeric Evaluation scores were 97.97 (98.33-100),
      96.4 (91-99), and 95 (90-100), respectively. One patient required implant
      removal. Fracture-specific plating with suture-button augmentation for type II
      distal clavicle fractures provides reliable rates of union without absolute
      requirement for implant removal.

PMID- 24667804
TI  - The effect of preoperative counseling on duration of postoperative opiate use in
      orthopaedic trauma surgery: a surgeon-based comparative cohort study.
AB  - OBJECTIVE: The prudent use of prescription opiates is a central aspect of current
      postsurgical pain management, but surgeons have no guidelines on appropriate
      duration of opiate treatment. Furthermore, there are no established data on the
      effect of physician counseling on the duration of opiate use postoperatively.
      DESIGN: Retrospective surgeon-controlled cohort study. SETTING: Level I regional
      academic trauma center. PATIENTS: All Utah residents admitted to the orthopaedic
      trauma service with isolated operative musculoskeletal injury. INTERVENTION: One
      group of patients was instructed at the time of index procedure that they would
      receive prescription opiates for a maximum of 6 weeks. The remaining patients
      were not counseled preoperatively on duration of opiate use postoperatively. MAIN
      OUTCOME MEASURES: The presence and frequency of prescription opiate use before
      injury, cessation of opiate use by 6 weeks postoperatively, cessation of opiates
      by 12 weeks postoperatively, and continuation of prescription opiates greater
      than 12 weeks postoperatively. RESULTS: Six hundred thirteen patients met
      inclusion criteria. Those counseled preoperatively to cease opiate use by 6 weeks
      were significantly more likely to do so than those who did not receive counseling
      (73% and 64%, respectively; P = 0.012). By 12 weeks, this effect was no longer
      seen, and patients were just as likely to have stopped (80% and 80%,
      respectively; P = 0.90). CONCLUSIONS: The orthopaedic trauma population is
      significantly more likely than the general population to be using prescription
      opiates before injury. Physician discussion of 6-week opiate prescription
      limitation at the time of injury seems to lead to a lower rate of use at the 6
      week postoperative mark but has no effect on rates of longer-term use. Twenty
      percent of patients in either group will continue to use opiates after 12 weeks,
      compared with 15% before injury. Given the scope of prescription opiate use in
      the United States, surgeons may want to consider preoperative discussion of this
      issue, but it may not have any effect on usage rates at longer intervals. LEVEL
      OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24667805
TI  - Forced resurgence and targeting of intracellular uropathogenic Escherichia coli
      reservoirs.
AB  - Intracellular quiescent reservoirs of uropathogenic Escherichia coli (UPEC),
      which can seed the bladder mucosa during the acute phase of a urinary tract
      infection (UTI), are protected from antibiotic treatments and are extremely
      difficult to eliminate. These reservoirs are a potential source for recurrent
      UTIs that affect millions annually. Here, using murine infection models and the
      bladder cell exfoliant chitosan, we demonstrate that intracellular UPEC
      populations shift within the stratified layers of the urothelium during the
      course of a UTI. Following invasion of the terminally differentiated superficial
      layer of epithelial cells that line the bladder lumen, UPEC can multiply and
      disseminate, eventually establishing reservoirs within underlying immature host
      cells. If given access, UPEC can invade the superficial and immature bladder
      cells equally well. As infected immature host cells differentiate and migrate
      towards the apical surface of the bladder, UPEC can reinitiate growth and
      discharge into the bladder lumen. By inducing the exfoliation of the superficial
      layers of the urothelium, chitosan stimulates rapid regenerative processes and
      the reactivation and efflux of quiescent intracellular UPEC reservoirs. When
      combined with antibiotics, chitosan treatment significantly reduces bacterial
      loads within the bladder and may therefore be of therapeutic value to individuals
      with chronic, recurrent UTIs. 

PMID- 24667806
TI  - A comprehensive system for generation and evaluation of induced pluripotent stem
      cells using piggyBac transposition.
AB  - The most stringent criterion for evaluating pluripotency is generation of
      chimeric animals with germline transmission ability. Because the quality of
      induced pluripotent stem cell (iPSC) lines is heterogeneous, an easy and accurate
      system to evaluate these abilities would be useful. In this study, we describe a
      simple but comprehensive system for generating and evaluating iPSCs by single
      transfection of multiple piggyBac (PB) plasmid vectors encoding Tet-inducible
      polycistronic reprogramming factors, a pluripotent-cell-specific reporter, a
      constitutively active reporter, and a sperm-specific reporter. Using this system,
      we reprogrammed 129 and NOD mouse embryonic fibroblasts into iPSCs, and then
      evaluated the molecular and functional properties of the resultant iPSCs by
      quantitative RT-PCR analysis and chimera formation assays. The iPSCs contributed
      extensively to chimeras, as indicated by the constitutively active TagRFP
      reporter, and also differentiated into sperm, as indicated by the late
      spermatogenesis-specific Acr (acrosin)-EGFP reporter. Next, we established
      secondary MEFs from E13.5 chimeric embryos and efficiently generated secondary
      iPSCs by simple addition of doxycycline. Finally, we applied this system to
      establishment and evaluation of rat iPSCs and production of rat sperm in mouse
      rat interspecific chimeras. By monitoring the fluorescence of Acr-EGFP reporter,
      we could easily detect seminiferous tubules containing rat iPSC-derived
      spermatids and sperm. And, we succeeded to obtain viable offspring by
      intracytoplasmic sperm injection (ICSI) using these haploid male germ cells. We
      propose that this system will enable robust strategies for induction and
      evaluation of iPSCs, not only in rodents but also in other mammals. Such
      strategies will be especially valuable in non-rodent species, in which
      verification of germline transmission by mating is inefficient and time
      consuming. 

PMID- 24667808
TI  - A transgenic platform for testing drugs intended for reversal of cardiac
      remodeling identifies a novel 11betaHSD1 inhibitor rescuing hypertrophy
      independently of re-vascularization.
AB  - RATIONALE: Rescuing adverse myocardial remodeling is an unmet clinical goal and,
      correspondingly, pharmacological means for its intended reversal are urgently
      needed. OBJECTIVES: To harness a newly-developed experimental model
      recapitulating progressive heart failure development for the discovery of new
      drugs capable of reversing adverse remodeling. METHODS AND RESULTS: A VEGF-based
      conditional transgenic system was employed in which an induced perfusion deficit
      and a resultant compromised cardiac function lead to progressive remodeling and
      eventually heart failure. Ability of candidate drugs administered at sequential
      remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac
      function was monitored. Arguing for clinical relevance of the experimental
      system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone
      System (RAAS), namely, the ACE inhibitor Enalapril and the direct renin inhibitor
      Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not
      accompanied by neovascularization and reached a point-of-no-return. Similarly,
      the PPARgamma agonist Pioglitazone was proven capable of reversing all aspects of
      cardiac remodeling without affecting the vasculature. Extending the arsenal of
      remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of
      11beta-hydroxy-steroid dehydrogenase type 1 (11beta HSD1), a key enzyme required
      for generating active glucocorticoids, fully rescued myocardial hypertrophy. This
      was associated with mitigating the hypertrophy-associated gene signature,
      including reversing the myosin heavy chain isoform switch but in a pattern
      distinguishable from that associated with neovascularization-induced reversal.
      CONCLUSIONS: A system was developed suitable for identifying novel remodeling
      reversing drugs operating in different pathways and for gaining insights into
      their mechanisms of action, exemplified here by uncoupling their vascular
      affects.

PMID- 24667809
TI  - Paying for express checkout: competition and price discrimination in multi-server
      queuing systems.
AB  - We model competition between two firms selling identical goods to customers who
      arrive in the market stochastically. Shoppers choose where to purchase based upon
      both price and the time cost associated with waiting for service. One seller
      provides two separate queues, each with its own server, while the other seller
      has a single queue and server. We explore the market impact of the multi-server
      seller engaging in waiting cost-based-price discrimination by charging a premium
      for express checkout. Specifically, we analyze this situation computationally and
      through the use of controlled laboratory experiments. We find that this form of
      price discrimination is harmful to sellers and beneficial to consumers. When the
      two-queue seller offers express checkout for impatient customers, the single
      queue seller focuses on the patient shoppers thereby driving down prices and
      profits while increasing consumer surplus. 

PMID- 24667807
TI  - Streptococcus suis infection: an emerging/reemerging challenge of bacterial
      infectious diseases?
AB  - Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial
      strains that represents a primary health problem in the swine industry worldwide.
      S. suis is also an emerging zoonotic pathogen that causes severe human infections
      clinically featuring with varied diseases/syndromes (such as meningitis,
      septicemia, and arthritis). Over the past few decades, continued efforts have
      made significant progress toward better understanding this zoonotic infectious
      entity, contributing in part to the elucidation of the molecular mechanism
      underlying its high pathogenicity. This review is aimed at presenting an updated
      overview of this pathogen from the perspective of molecular epidemiology,
      clinical diagnosis and typing, virulence mechanism, and protective antigens
      contributing to its zoonosis. 

PMID- 24667811
TI  - Soft ferromagnetism in mixed valence Sr(1-x)La(x)Ti(0.5)Mn(0.5)O3 perovskites.
AB  - The structural, magnetic and electrical properties of the mixed Ti-Mn oxides Sr(1
      x)La(x)Ti(0.5)Mn(0.5)O3 (0 <= x <= 0.5) are reported. At room temperature the
      oxides have a cubic structure in space group Pm3m for x <= 0.25 and rhombohedral
      in R3c for 0.3 <= x <= 0.50. X-ray absorption spectroscopic measurements
      demonstrate the addition of La(3+) is compensated by the partial reduction of
      Mn(4+) to Mn(3+). Variable temperature neutron diffraction measurements show that
      cooling Sr(0.6)La(0.4)Ti(0.5)Mn(0.5)O3 results in a first order transition from
      rhombohedra to an orthorhombic structure in Imma. Complex magnetic behaviour is
      observed. The magnetic behaviour of the mixed valent (Mn(3+/4+)) examples is
      dominated by ferromagnetic interactions, although cation disorder frustrates long
      range magnetic ordering.

PMID- 24667810
TI  - Water, sanitation, hygiene, and soil-transmitted helminth infection: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Preventive chemotherapy represents a powerful but short-term control
      strategy for soil-transmitted helminthiasis. Since humans are often re-infected
      rapidly, long-term solutions require improvements in water, sanitation, and
      hygiene (WASH). The purpose of this study was to quantitatively summarize the
      relationship between WASH access or practices and soil-transmitted helminth (STH)
      infection. METHODS AND FINDINGS: We conducted a systematic review and meta
      analysis to examine the associations of improved WASH on infection with STH
      (Ascaris lumbricoides, Trichuris trichiura, hookworm [Ancylostoma duodenale and
      Necator americanus], and Strongyloides stercoralis). PubMed, Embase, Web of
      Science, and LILACS were searched from inception to October 28, 2013 with no
      language restrictions. Studies were eligible for inclusion if they provided an
      estimate for the effect of WASH access or practices on STH infection. We assessed
      the quality of published studies with the Grades of Recommendation, Assessment,
      Development and Evaluation (GRADE) approach. A total of 94 studies met our
      eligibility criteria; five were randomized controlled trials, whilst most others
      were cross-sectional studies. We used random-effects meta-analyses and analyzed
      only adjusted estimates to help account for heterogeneity and potential
      confounding respectively. Use of treated water was associated with lower odds of
      STH infection (odds ratio [OR] 0.46, 95% CI 0.36-0.60). Piped water access was
      associated with lower odds of A. lumbricoides (OR 0.40, 95% CI 0.39-0.41) and T.
      trichiura infection (OR 0.57, 95% CI 0.45-0.72), but not any STH infection (OR
      0.93, 95% CI 0.28-3.11). Access to sanitation was associated with decreased
      likelihood of infection with any STH (OR 0.66, 95% CI 0.57-0.76), T. trichiura
      (OR 0.61, 95% CI 0.50-0.74), and A. lumbricoides (OR 0.62, 95% CI 0.44-0.88), but
      not with hookworm infection (OR 0.80, 95% CI 0.61-1.06). Wearing shoes was
      associated with reduced odds of hookworm infection (OR 0.29, 95% CI 0.18-0.47)
      and infection with any STH (OR 0.30, 95% CI 0.11-0.83). Handwashing, both before
      eating (OR 0.38, 95% CI 0.26-0.55) and after defecating (OR 0.45, 95% CI 0.35
      0.58), was associated with lower odds of A. lumbricoides infection. Soap use or
      availability was significantly associated with lower infection with any STH (OR
      0.53, 95% CI 0.29-0.98), as was handwashing after defecation (OR 0.47, 95% CI
      0.24-0.90). Observational evidence constituted the majority of included
      literature, which limits any attempt to make causal inferences. Due to underlying
      heterogeneity across observational studies, the meta-analysis results reflect an
      average of many potentially distinct effects, not an average of one specific
      exposure-outcome relationship. CONCLUSIONS: WASH access and practices are
      generally associated with reduced odds of STH infection. Pooled estimates from
      all meta-analyses, except for two, indicated at least a 33% reduction in odds of
      infection associated with individual WASH practices or access. Although most WASH
      interventions for STH have focused on sanitation, access to water and hygiene
      also appear to significantly reduce odds of infection. Overall quality of
      evidence was low due to the preponderance of observational studies, though recent
      randomized controlled trials have further underscored the benefit of handwashing
      interventions. Limited use of the Joint Monitoring Program's standardized water
      and sanitation definitions in the literature restricted efforts to generalize
      across studies. While further research is warranted to determine the magnitude of
      benefit from WASH interventions for STH control, these results call for multi
      sectoral, integrated intervention packages that are tailored to social-ecological
      contexts.

PMID- 24667812
TI  - Lactulose increases equol production and improves liver antioxidant status in
      barrows treated with Daidzein.
AB  - Equol, one of the intestinal microflora metabolites of daidzein, has gained much
      attention for having greater bioactivity than its precursor (daidzein and
      daidzin) and seeming to be promoted by hydrogen gas. The effects of lactulose on
      the equol-producing capacity and liver antioxidant status of barrows treated with
      daidzein were investigated in this study. Male castrated piglets (barrows) of
      Landrace * Duroc, aged 40 days, were randomly divided into the following three
      groups: control group (C, n = 12, fed an isoflavones-free basic diet), daidzein
      group (D, n = 12, fed an isoflavones-free basic diet with 50 mg/kg of daidzein
      supplementation) and daidzein+lactulose group (D+L, n = 12, fed an isoflavones
      free basic diet with 1% of lactulose and 50 mg/kg of daidzein supplementation).
      After 20 days, the profile of short-chain fatty acids in the colon digesta showed
      that lactulose significantly increased the fermented capacity in the
      gastrointestinal tract of the barrows. First-void urinary equol concentrations
      were significantly higher in the D+L group than in the D group (3.13 +/- 0.93
      compared to 2.11 +/- 0.82 MUg/ml, respectively). Furthermore, fecal equol levels
      were also significantly higher in the D+L group than in the D group (12.00 +/-
      2.68 compared to 10.00 +/- 2.26 MUg/g, respectively). The population of
      bacteroidetes and the percentage of bacteroidetes to bacteria in feces were
      higher in the D+L group than in the D group. The DGGE profiles results indicate
      that lactulose might shift the pathways of hydrogen utilization, and changing the
      profiles of SRB in feces. Moreover, the D+L group had weak enhancement of T-SOD
      and CuZn-SOD activities in the livers of barrows treated with daidzein.

PMID- 24667813
TI  - The VACS index accurately predicts mortality and treatment response among multi
      drug resistant HIV infected patients participating in the options in management
      with antiretrovirals (OPTIMA) study.
AB  - OBJECTIVES: The VACS Index is highly predictive of all-cause mortality among HIV
      infected individuals within the first few years of combination antiretroviral
      therapy (cART). However, its accuracy among highly treatment experienced
      individuals and its responsiveness to treatment interventions have yet to be
      evaluated. We compared the accuracy and responsiveness of the VACS Index with a
      Restricted Index of age and traditional HIV biomarkers among patients enrolled in
      the OPTIMA study. METHODS: Using data from 324/339 (96%) patients in OPTIMA, we
      evaluated associations between indices and mortality using Kaplan-Meier
      estimates, proportional hazards models, Harrel's C-statistic and net
      reclassification improvement (NRI). We also determined the association between
      study interventions and risk scores over time, and change in score and mortality.
      RESULTS: Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted
      mortality from baseline, but discrimination was improved with the VACS Index (NRI
      = 23%). Change in score from baseline to 48 weeks was more strongly associated
      with survival for the VACS Index than the Restricted Index with respective hazard
      ratios of 0.26 (95% CI 0.14-0.49) and 0.39(95% CI 0.22-0.70) among the 25% most
      improved scores, and 2.08 (95% CI 1.27-3.38) and 1.51 (95%CI 0.90-2.53) for the
      25% least improved scores. CONCLUSIONS: The VACS Index predicts all-cause
      mortality more accurately among multi-drug resistant, treatment experienced
      individuals and is more responsive to changes in risk associated with treatment
      intervention than an index restricted to age and HIV biomarkers. The VACS Index
      holds promise as an intermediate outcome for intervention research.

PMID- 24667814
TI  - High-sensitivity C-reactive protein predicts mortality and technique failure in
      peritoneal dialysis patients.
AB  - INTRODUCTION: An elevated level of serum C-reactive protein (CRP) is widely
      considered an indicator of an underlying inflammatory disease and a long-term
      prognostic predictor for dialysis patients. This cross-sectional cohort study was
      designed to assess the correlation between the level of high-sensitivity CRP (HS
      CRP) and the outcome of peritoneal dialysis (PD) patients. METHODS: A total of
      402 patients were stratified into 3 tertiles (lower, middle, upper) according to
      serum HS-CRP level and and followed up from October 2009 to September 2011.
      During follow-up, cardiovascular events, infection episodes, technique failure,
      and mortality rate were recorded. RESULTS: During the 24-month follow-up, 119 of
      402 patients (29.6%) dropped out from PD, including 28 patients (7.0%) who died,
      81 patients (20.1%) who switched to hemodialysis, and 10 patients (2.5%) who
      underwent kidney transplantation. The results of Kaplan-Meier analysis and log
      rank test demonstrated a significant difference in the cumulative patient
      survival rate across the 3 tertiles (the lowest rate in upper tertile). On
      multivariate Cox regression analysis, only higher HS-CRP level, older age, the
      presence of diabetes mellitus (DM), lower serum albumin level, and the occurrence
      of cardiovascular events during follow-up were identified as independent
      predictors of mortality. Every 1 mg/L increase in HS-CRP level was independently
      predictive of a 1.4% increase in mortality. Multivariate Cox regression analysis
      also showed that higher HS-CRP level, the presence of DM, lower hemoglobin level,
      lower serum albumin level, higher dialysate/plasma creatinine ratio, and the
      occurrence of infective episodes and cardiovascular events during follow-up were
      independent predictors of technique failure. CONCLUSIONS: The present study shows
      the importance of HS-CRP in the prediction of 2-year mortality and technique
      survival in PD patients independent of age, diabetes, hypoalbuminemia, and the
      occurrence of cardiovascular events.

PMID- 24667815
TI  - Polymorphisms at residue 222 of the hemagglutinin of pandemic influenza
      A(H1N1)pdm09: association of quasi-species to morbidity and mortality in
      different risk categories.
AB  - The D222G substitution in the hemagglutinin (HA) gene of the pandemic influenza
      A(H1N1)pdm09 virus has been identified as a potential virulence marker, because
      this change allows for virus invasion deeper into the respiratory tract. In this
      study, we analyzed D, G and N polymorphisms at residue 222 by pyrosequencing
      (PSQ). We initially analyzed 401 samples from Brazilian patients. These were
      categorized with respect to clinical conditions due to influenza infection (mild,
      serious or fatal) and sub-stratified by risky factors. The frequency of mixed
      population of virus, with more than one polymorphism at residue 222, was
      significantly higher in serious (10.6%) and fatal (46.7%) influenza cases,
      whereas those who showed mild influenza infections were all infected by D222 wild
      type. Mixtures of quasi-species showed a significant association of mortality,
      especially for those with risk factors, in special pregnant women. These results
      not only reinforce the association between D222G substitution and influenza
      A(H1N1)pdm09-associated morbidity and mortality, but also add the perspective
      that a worse clinical prognosis is most likely correlated with mixtures of quasi
      species at this HA residue. Therefore, quasi-species may have a critical and
      underestimated role in influenza-related clinical outcomes. 

PMID- 24667816
TI  - Skeletal muscle DNA damage precedes spinal motor neuron DNA damage in a mouse
      model of Spinal Muscular Atrophy (SMA).
AB  - Spinal Muscular Atrophy (SMA) is a hereditary childhood disease that causes
      paralysis by progressive degeneration of skeletal muscles and spinal motor
      neurons. SMA is associated with reduced levels of full-length Survival of Motor
      Neuron (SMN) protein, due to mutations in the Survival of Motor Neuron 1 gene.
      The mechanisms by which lack of SMN causes SMA pathology are not known, making it
      very difficult to develop effective therapies. We investigated whether DNA damage
      is a perinatal pathological event in SMA, and whether DNA damage and cell death
      first occur in skeletal muscle or spinal cord of SMA mice. We used a mouse model
      of severe SMA to ascertain the extent of cell death and DNA damage throughout the
      body of prenatal and newborn mice. SMA mice at birth (postnatal day 0) exhibited
      internucleosomal fragmentation in genomic DNA from hindlimb skeletal muscle, but
      not in genomic DNA from spinal cord. SMA mice at postnatal day 5, compared with
      littermate controls, exhibited increased apoptotic cell death profiles in
      skeletal muscle, by hematoxylin and eosin, terminal deoxynucleotidyl transferase
      dUTP nick end labeling, and electron microscopy. SMA mice had no increased cell
      death, no loss of choline acetyl transferase (ChAT)-positive motor neurons, and
      no overt pathology in the ventral horn of the spinal cord. At embryonic days 13
      and 15.5, SMA mice did not exhibit statistically significant increases in cell
      death profiles in spinal cord or skeletal muscle. Motor neuron numbers in the
      ventral horn, as identified by ChAT immunoreactivity, were comparable in SMA mice
      and control littermates at embryonic day 15.5 and postnatal day 5. These
      observations demonstrate that in SMA, disease in skeletal muscle emerges before
      pathology in spinal cord, including loss of motor neurons. Overall, this work
      identifies DNA damage and cell death in skeletal muscle as therapeutic targets
      for SMA. 

PMID- 24667819
TI  - Structural alteration of the metal-organic pyrogallol[4]arene nano-capsule motif
      by incorporation of large metal centres.
AB  - Addition of cadmium(II) nitrate to gallium-coordinated metal-organic C
      alkylpyrogallol[4]arene nano-capsules affords a variation of the near spherical
      hexamer motif, structural changes in which are induced by the markedly different
      nature of the secondary incorporated metal.

PMID- 24667818
TI  - Protective role for properdin in progression of experimental murine
      atherosclerosis.
AB  - Genetic, dietary and immune factors contribute to the pathogenesis of
      atherosclerosis in humans and mice. Complement activation is an integral part of
      the innate immune defence but also shapes cellular responses and influences
      directly triglyceride synthesis. Deficiency of Factor B of the alternative
      pathway (AP) of complement is beneficial in LDLR(-/-) mice fed a high fat diet.
      The serum glycoprotein properdin is a key positive regulator of the AP but has
      not been studied in experimental atherosclerosis. Atherosclerosis was assessed
      after feeding low fat (LFD) or high fat (HFD) Western type diets to newly
      generated LDLR(-/-) Properdin(KO) (LDLR(-/-)P(KO)) and LDLR-/-PWT mice. Lipids,
      lymphocytes and monocytes were similar among genotypes, genders and diets.
      Complement C3, but not C3adesarg, levels were enhanced in LDLR(-/-)P(KO) mice
      regardless of diet type or gender. Non-esterified fatty acids (NEFA) were
      decreased in male LDLR(-/-)P(KO) fed a HFD compared with controls. All mice
      showed significant atherosclerotic burden in aortae and at aortic roots but male
      LDLR(-/-) mice fed a LFD were affected to the greatest extent by the absence of
      properdin. The protective effect of properdin expression was overwhelmed in both
      genders of LDLR(-/-)mice when fed a HFD. We conclude that properdin plays an
      unexpectedly beneficial role in the development and progression of early
      atherosclerotic lesions.

PMID- 24667817
TI  - Low doses of gamma-irradiation induce an early bystander effect in zebrafish
      cells which is sufficient to radioprotect cells.
AB  - The term "bystander effect" is used to describe an effect in which cells that
      have not been exposed to radiation are affected by irradiated cells though
      various intracellular signaling mechanisms. In this study we analyzed the
      kinetics and mechanisms of bystander effect and radioadaptation in embryonic
      zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were
      irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01
      0.1 Gy. In two experimental conditions, the transfer of irradiated cells or
      culture medium from irradiated cells results in the occurrence of DNA double
      strand breaks in non-irradiated cells (assessed by the number of gamma-H2AX foci)
      that are repaired at 24 hours post-irradiation whatever the dose. At low total
      irradiation doses the bystander effect observed does not affect DNA repair
      mechanisms in targeted and bystander cells. An increase in global methylation of
      ZF4 cells was observed in irradiated cells and bystander cells compared to
      control cells. We observed that pre-irradiated cells which are then irradiated
      for a second time with the same doses contained significantly less gamma-H2AX
      foci than in 24 h gamma-irradiated control cells. We also showed that bystander
      cells that have been in contact with the pre-irradiated cells and then irradiated
      alone present less gamma-H2AX foci compared to the control cells. This
      radioadaptation effect is significantly more pronounced at the highest doses. To
      determine the factors involved in the early events of the bystander effect, we
      performed an extensive comparative proteomic study of the ZF4 secretomes upon
      irradiation. In the experimental conditions assayed here, we showed that the
      early events of bystander effect are probably not due to the secretion of
      specific proteins neither the oxidation of these secreted proteins. These results
      suggest that early bystander effect may be due probably to a combination of
      multiple factors. 

PMID- 24667820
TI  - Characterization of bonds formed between platelet factor 4 and negatively charged
      drugs using single molecule force spectroscopy.
AB  - Immunogenicity (i.e., the ability to initiate immune reactions) is one of the
      major challenges for the development of new drugs, as it may turn the developed
      drug therapeutically ineffective or cause severe immune-related effects. Using
      single molecule force spectroscopy, we study rupture forces between the
      positively charged, endogenous protein platelet factor 4 (PF4; also known as CXC
      chemokine ligand 4, CXCL4) and the antithrombotic drug heparin and other
      negatively charged glycosaminoglycans (GAGs), which are known to form immunogenic
      PF4/GAG-complexes (e.g., heparin and dextran sulfate) as well as non-immunogenic
      complexes (e.g., chondroitin sulfate A). Our measurements suggest that the
      average number of sulfate groups per monosaccharide unit (i.e., the degree of
      sulfation DS) does not affect the unbinding characteristics of single PF4/GAG
      bonds (reaction coordinate x0 = 2.2 +/- 0.2 A, energy barrier DeltaG ~ -1 kBT).
      However, the average number of GAG bonds formed to a single PF4 molecule
      increases with increasing DS as indicated by a rising frequency of unbinding
      events, suggesting a multivalent binding scheme between PF4 and GAGs. Our studies
      show that at least three GAG bonds have to be formed to each PF4 molecule to
      induce epitope formation on the PF4/GAG-complex to which PF4/GAG-complex specific
      antibodies bind. Hence, GAG-based drugs that form less than three bonds per PF4
      molecule are unlikely to constitute PF4/drug-complexes that are of immunologic
      relevance. 

PMID- 24667821
TI  - Sexually dimorphic body color is regulated by sex-specific expression of yellow
      gene in ponerine ant, Diacamma sp.
AB  - Most hymenopteran species exhibit conspicuous sexual dimorphism due to ecological
      differences between the sexes. As hymenopteran genomes, under the haplodiploid
      genetic system, exhibit quantitative differences between sexes while remaining
      qualitatively identical, sexual phenotypes are assumed to be expressed through
      sex-specific gene usage. In the present study, the molecular basis for expression
      of sexual dimorphism in a queenless ant, Diacamma sp., which exhibits a distinct
      color dimorphism, was examined. Worker females of the species appear bluish
      black, while winged males exhibit a yellowish-brown body color. Initially,
      observations of the pigmentation processes during pupal development revealed that
      black pigmentation was present in female pupae but not in males, suggesting that
      sex-specific melanin synthesis was responsible for the observed color dimorphism.
      Therefore, five orthologs of the genes involved in the insect melanin synthesis
      (yellow, ebony, tan, pale and dopa decarboxylase) were subcloned and their
      spatiotemporal expression patterns were examined using real-time quantitative RT
      PCR. Of the genes examined, yellow, which plays a role in black melanin synthesis
      in insects, was expressed at higher levels in females than in males throughout
      the entire body during the pupal stage. RNA interference of yellow was then
      carried out in order to determine the gene function, and produced females with a
      more yellowish, brighter body color similar to that of males. It was concluded
      that transcriptional regulation of yellow was responsible for the sexual color
      dimorphism observed in this species. 

PMID- 24667822
TI  - Diagnostic value of direct fluorescence antibody staining for detecting
      Pneumocystis jirovecii in expectorated sputum from patients with HIV infection.
AB  - Direct fluorescent antibody (DFA) staining of induced sputum is frequently used
      to diagnose Pneumocystis pneumonia (PCP) in patients infected with human
      immunodeficiency virus, although induction can provoke nausea and bronchospasm.
      Since the diagnostic value of expectorated sputum examined with DFA stain has not
      been well evaluated, we reviewed the medical records of HIV-infected patients who
      were clinically diagnosed as having PCP between 1999 and 2011. Over this 13-year
      period, we found 76 patients whose records included the results of DFA staining
      of expectorated sputum and noted that 42 (55.3%) were positive. Polymerase chain
      reaction to detect Pneumocystis in the sputum of 65 of the patients resulted in
      the finding of 43 (66.2%) who were positive. Our findings suggest that DFA
      staining of expectorated sputum could be a useful initial diagnostic method in
      HIV-infected patients with PCP. 

PMID- 24667823
TI  - The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D
      concentrations adjusted for albumin.
AB  - BACKGROUND: Plasma 25-hydroxyvitamin D (25(OH) D) deficiencies are associated
      with several diseases. The magnitude of systemic inflammatory response, as
      evidenced by C-reactive protein (CRP), is a major factor associated with lower
      25(OH)D. Other aspects of the systemic inflammatory response may be important in
      determining plasma 25 (OH)D concentrations. AIM: To examine the relationship
      between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts.
      METHODS: 5327 patients referred for nutritional assessment and 117 patients with
      critical illness were examined. Plasma 25 (OH) D concentrations were measured
      using standard methods. Intra and between assay imprecision was <10%. RESULT: In
      the large cohort, plasma 25 (OH) D was significantly associated with CRP (r(s)  =
      -0.113, p<0.001) and albumin (rs = 0.192, p<0.001). 3711 patients had CRP
      concentrations <= 10 mg/L; with decreasing albumin concentrations >= 35, 25-34
      and <25 g/l, median concentrations of 25 (OH) D were significantly lower from 35
      to 28 to 14 nmol/l (p<0.001). This decrease was significant when albumin
      concentrations were reduced between 25-34 g/L (p<0.001) and when albumin <25 g/L
      (p<0.001). 1271 patients had CRP concentrations between 11-80 mg/L; with
      decreasing albumin concentrations >= 35, 25-34 and <25 g/l, median concentrations
      of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p<0.001). This
      decrease was significant when albumin concentration were 25-34 g/L (p<0.001) and
      when albumin <25 g/L (p<0.001). 345 patients had CRP concentrations >80 mg/L;
      with decreasing albumin concentrations >= 35, 25-34 and <25 g/l, median
      concentrations of 25 (OH) D were not significantly altered varying from 19 to 23
      to 23 nmol/l. Similar relationships were also obtained in the cohort of patients
      with critical illness. CONCLUSION: Plasma concentrations of 25(OH) D were
      independently associated with both CRP and albumin and consistent with the
      systemic inflammatory response as a major confounding factor in determining
      vitamin D status.

PMID- 24667824
TI  - Microsatellite marker analysis reveals the complex phylogeographic history of
      Rhododendron ferrugineum (Ericaceae) in the Pyrenees.
AB  - Genetic variation within plant species is determined by a number of factors such
      as reproductive mode, breeding system, life history traits and climatic events.
      In alpine regions, plants experience heterogenic abiotic conditions that
      influence the population's genetic structure. The aim of this study was to
      investigate the genetic structure and phylogeographic history of the subalpine
      shrub Rhododendron ferrugineum across the Pyrenees and the links between the
      populations in the Pyrenees, the Alps and Jura Mountains. We used 27
      microsatellite markers to genotype 645 samples from 29 Pyrenean populations,
      three from the Alps and one from the Jura Mountains. These data were used to
      estimate population genetics statistics such as allelic richness, observed
      heterozygosity, expected heterozygosity, fixation index, inbreeding coefficient
      and number of migrants. Genetic diversity was found to be higher in the Alps than
      in the Pyrenees suggesting colonization waves from the Alps to the Pyrenees. Two
      separate genetic lineages were found in both the Alps and Pyrenees, with a
      substructure of five genetic clusters in the Pyrenees where a loss of genetic
      diversity was noted. The strong differentiation among clusters is maintained by
      low gene flow across populations. Moreover, some populations showed higher
      genetic diversity than others and presented rare alleles that may indicate the
      presence of alpine refugia. Two lineages of R. ferrugineum have colonized the
      Pyrenees from the Alps. Then, during glaciation events R. ferrugineum survived in
      the Pyrenees in different refugia such as lowland refugia at the eastern part of
      the chain and nunataks at high elevations leading to a clustered genetic pattern.

PMID- 24667825
TI  - A resource-based modelling framework to assess habitat suitability for steppe
      birds in semiarid Mediterranean agricultural systems.
AB  - European agriculture is undergoing widespread changes that are likely to have
      profound impacts on farmland biodiversity. The development of tools that allow an
      assessment of the potential biodiversity effects of different land-use
      alternatives before changes occur is fundamental to guiding management decisions.
      In this study, we develop a resource-based model framework to estimate habitat
      suitability for target species, according to simple information on species' key
      resource requirements (diet, foraging habitat and nesting site), and examine
      whether it can be used to link land-use and local species' distribution. We take
      as a study case four steppe bird species in a lowland area of the north-eastern
      Iberian Peninsula. We also compare the performance of our resource-based approach
      to that obtained through habitat-based models relating species' occurrence and
      land-cover variables. Further, we use our resource-based approach to predict the
      effects that change in farming systems can have on farmland bird habitat
      suitability and compare these predictions with those obtained using the habitat
      based models. Habitat suitability estimates generated by our resource-based
      models performed similarly (and better for one study species) than habitat based
      models when predicting current species distribution. Moderate prediction success
      was achieved for three out of four species considered by resource-based models
      and for two of four by habitat-based models. Although, there is potential for
      improving the performance of resource-based models, they provide a structure for
      using available knowledge of the functional links between agricultural practices,
      provision of key resources and the response of organisms to predict potential
      effects of changing land-uses in a variety of context or the impacts of changes
      such as altered management practices that are not easily incorporated into
      habitat-based models. 

PMID- 24667826
TI  - Do adults show a curse of knowledge in false-belief reasoning? A robust estimate
      of the true effect size.
AB  - Seven experiments use large sample sizes to robustly estimate the effect size of
      a previous finding that adults are more likely to commit egocentric errors in a
      false-belief task when the egocentric response is plausible in light of their
      prior knowledge. We estimate the true effect size to be less than half of that
      reported in the original findings. Even though we found effects in the same
      direction as the original, they were substantively smaller; the original study
      would have had less than 33% power to detect an effect of this magnitude. The
      influence of plausibility on the curse of knowledge in adults appears to be small
      enough that its impact on real-life perspective-taking may need to be
      reevaluated. 

PMID- 24667827
TI  - On the road towards electroactive covalent organic frameworks.
AB  - Covalent organic frameworks (COFs) are a novel class of porous crystalline
      organic materials assembled from molecular building blocks. The construction
      principles of these materials allow for the design of precisely controllable
      structures since their chemical and physical properties can be easily tuned
      through the selection of the building blocks and the linkage motif. Their
      extraordinary and versatile properties impart functionality that is of great
      interest in areas such as gas storage, separation, catalysis and optoelectronics.
      This feature article discusses key aspects of the design of covalent organic
      frameworks with a focus on electroactive COFs for potential optoelectronic and
      photovoltaic applications. 

PMID- 24667828
TI  - Open source software to control Bioflo bioreactors.
AB  - Bioreactors are designed to support highly controlled environments for growth of
      tissues, cell cultures or microbial cultures. A variety of bioreactors are
      commercially available, often including sophisticated software to enhance the
      functionality of the bioreactor. However, experiments that the bioreactor
      hardware can support, but that were not envisioned during the software design
      cannot be performed without developing custom software. In addition, support for
      third party or custom designed auxiliary hardware is often sparse or absent. This
      work presents flexible open source freeware for the control of bioreactors of the
      Bioflo product family. The functionality of the software includes setpoint
      control, data logging, and protocol execution. Auxiliary hardware can be easily
      integrated and controlled through an integrated plugin interface without altering
      existing software. Simple experimental protocols can be entered as a CSV
      scripting file, and a Python-based protocol execution model is included for more
      demanding conditional experimental control. The software was designed to be a
      more flexible and free open source alternative to the commercially available
      solution. The source code and various auxiliary hardware plugins are publicly
      available for download from https://github.com/LibourelLab/BiofloSoftware. In
      addition to the source code, the software was compiled and packaged as a self
      installing file for 32 and 64 bit windows operating systems. The compiled
      software will be able to control a Bioflo system, and will not require the
      installation of LabVIEW. 

PMID- 24667829
TI  - Simulator-based transesophageal echocardiographic training with motion analysis:
      a curriculum-based approach.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) is a complex endeavor
      involving both motor and cognitive skills. Current training requires extended
      time in the clinical setting. Application of an integrated approach for TEE
      training including simulation could facilitate acquisition of skills and
      knowledge. METHODS: Echo-naive nonattending anesthesia physicians were offered
      Web-based echo didactics and biweekly hands-on sessions with a TEE simulator for
      4 weeks. Manual skills were assessed weekly with kinematic analysis of TEE probe
      motion and compared with that of experts. Simulator-acquired skills were assessed
      clinically with the performance of intraoperative TEE examinations after
      training. Data were presented as median (interquartile range). RESULTS: The
      manual skills of 18 trainees were evaluated with kinematic analysis. Peak
      movements and path length were found to be independent predictors of proficiency
      (P < 0.01) by multiple regression analysis. Week 1 trainees had longer path
      length (637 mm [312 to 1,210]) than that of experts (349 mm [179 to 516]); P <
      0.01. Week 1 trainees also had more peak movements (17 [9 to 29]) than that of
      experts (8 [2 to 12]); P < 0.01. Skills acquired from simulator training were
      assessed clinically with eight additional trainees during intraoperative TEE
      examinations. Compared with the experts, novice trainees required more time (199
      s [193 to 208] vs. 87 s [83 to 16]; P = 0.002) and performed more transitions
      throughout the examination (43 [36 to 53] vs. 21 [20 to 23]; P = 0.004).
      CONCLUSIONS: A simulation-based TEE curriculum can teach knowledge and technical
      skills to echo-naive learners. Kinematic measures can objectively evaluate the
      progression of manual TEE skills.

PMID- 24667830
TI  - Emulsified isoflurane enhances thermal transient receptor potential vanilloid-1
      channel activation-mediated sensory/nociceptive blockade by QX-314.
AB  - BACKGROUND: QX-314 produces nociceptive blockade, facilitated by permeation
      through transient receptor potential vanilloid-1 (TRPV1) channels. TRPV1 channel
      can be activated by noxious heat and sensitized by volatile anesthetics. The
      authors hypothesized that emulsified isoflurane (EI) could enhance thermal TRPV1
      channel activation-mediated sensory/nociceptive blockade by QX-314. METHODS: Rats
      were perineurally injected with QX-314 (Sigma-Aldrich Co. Ltd. Shanghai, China)
      alone or QX-314 combined with EI, followed by heat exposure on the injection
      site. The tail-flick and tail-clamping tests were used to assess sensory and
      nociceptive blockade, respectively; a sciatic nerve block model was used to
      assess motor and sensory blockade. Effects of EI on thermal activation of TRPV1
      channels were evaluated on rat dorsal root ganglia neurons by whole-cell patch
      clamp recordings. RESULTS: Heat exposure enhanced sensory/nociceptive blockade by
      QX-314 in rat tails, but not motor blockade in sciatic nerve block model. QX-314
      alone or QX-314 + 42 degrees C produced no nociceptive blockade. QX-314 + 48
      degrees C produced 100% nociceptive blockade with duration of 12.5 +/- 2.0 h
      (mean +/- SEM). By adding 2% EI, QX-314 + 42 degrees C produced 80% nociceptive
      blockade with duration of 8.1 +/- 1.9 h, which was similar to the effect of QX
      314 + 46 degrees C (7.7 +/- 1.1 h; P = 0.781). The enhancement of heat on
      sensory/nociceptive blockade of QX-314 was prevented by TRPV1 channel antagonist.
      The temperature thresholds of TRPV1 channel activation on dorsal root ganglia
      neurons were significantly reduced by EI. CONCLUSIONS: Thermal activation of
      TRPV1 channels enhanced long-lasting sensory/nociceptive blockade by QX-314
      without affecting motor blockade. The addition of EI reduced temperature
      thresholds for inducing long-lasting sensory/nociceptive blockade due to QX-314.

PMID- 24667832
TI  - Dealing with consumer differences in liking during repeated exposure to food;
      typical dynamics in rating behavior.
AB  - Consumers show high interindividual variability in food liking during repeated
      exposure. To investigate consumer liking during repeated exposure, data is often
      interpreted on a product level by averaging results over all consumers. However,
      a single product may elicit inconsistent behaviors in consumers; averaging will
      mix and hide possible subgroups of consumer behaviors, leading to a
      misinterpretation of the results. To deal with the variability in consumer
      liking, we propose to use clustering on data from consumer-product combinations
      to investigate the nature of the behavioral differences within the complete
      dataset. The resulting behavioral clusters can then be used to describe product
      acceptance. To test this approach we used two independent data sets in which
      young adults were repeatedly exposed to drinks and snacks, respectively. We found
      that five typical consumer behaviors existed in both datasets. These behaviors
      differed both in the average level of liking as well as its temporal dynamics. By
      investigating the distribution of a single product across typical consumer
      behaviors, we provide more precise insight in how consumers divide in subgroups
      based on their product liking (i.e. product modality). This work shows that
      taking into account and using interindividual differences can unveil information
      about product acceptance that would otherwise be ignored. 

PMID- 24667831
TI  - Heat-shock response increases lung injury caused by Pseudomonas aeruginosa via an
      interleukin-10-dependent mechanism in mice.
AB  - BACKGROUND: The heat-shock response (HSR) protects from insults, such as ischemia
      reperfusion injury, by inhibiting signaling pathways activated by sterile
      inflammation. However, the mechanisms by which the HSR activation would modulate
      lung damage and host response to a bacterial lung infection remain unknown.
      METHODS: HSR was activated with whole-body hyperthermia or by intraperitoneal
      geldanamycin in mice that had their lungs instilled with Pseudomonas aeruginosa
      24 h later (at least six mice per experimental group). Four hours after
      instillation, lung endothelial and epithelial permeability, bacterial counts,
      protein levels in bronchoalveolar lavage fluid, and lung myeloperoxidase activity
      were measured. Mortality rate 24 h after P. aeruginosa instillation was recorded.
      The HSR effect on the release of interleukin-10 and killing of P. aeruginosa
      bacteria by a mouse alveolar macrophage cell line and on neutrophil phagocytosis
      was also examined. RESULTS: HSR activation worsened lung endothelial (42%) and
      epithelial permeability (50%) to protein, decreased lung bacterial clearance
      (71%), and increased mortality (50%) associated with P. aeruginosa pneumonia, an
      effect that was not observed in heat-shock protein-72-null mice. HSR-mediated
      decrease in neutrophil phagocytosis (69%) and bacterial killing (38%) by
      macrophages was interleukin-10 dependent, a mechanism confirmed by increased lung
      bacterial clearance and decreased mortality (70%) caused by P. aeruginosa
      pneumonia in heat-shocked interleukin-10-null mice. CONCLUSIONS: Prior HSR
      activation worsens lung injury associated with P. aeruginosa pneumonia in mice
      via heat-shock protein-72- and interleukin-10-dependent mechanisms. These results
      provide a novel mechanism for the immunosuppression observed after severe trauma
      that is known to activate HSR in humans.

PMID- 24667833
TI  - Searching for signatures of cold adaptations in modern and archaic humans: hints
      from the brown adipose tissue genes.
AB  - Adaptation to low temperatures has been reasonably developed in the human species
      during the colonization of the Eurasian landmass subsequent to Out of Africa
      migrations of anatomically modern humans. In addition to morphological and
      cultural changes, also metabolic ones are supposed to have favored human
      isolation from cold and body heat production and this can be hypothesized also
      for most Neandertal and at least for some Denisovan populations, which lived in
      geographical areas that strongly experienced the last glacial period. Modulation
      of non-shivering thermogenesis, for which adipocytes belonging to the brown
      adipose tissue are the most specialized cells, might have driven these metabolic
      adaptations. To perform an exploratory analysis aimed at looking into this
      hypothesis, variation at 28 genes involved in such functional pathway was
      investigated in modern populations from different climate zones, as well as in
      Neandertal and Denisovan genomes. Patterns of variation at the LEPR gene,
      strongly related to increased heat dissipation by mitochondria, appeared to have
      been shaped by positive selection in modern East Asians, but not in Europeans.
      Moreover, a single potentially cold-adapted LEPR allele, different from the
      supposed adaptive one identified in Homo sapiens, was found also in Neandertal
      and Denisovan genomes. These findings suggest that independent mechanisms for
      cold adaptations might have been developed in different non-African human groups,
      as well as that the evolution of possible enhanced thermal efficiency in
      Neandertals and in some Denisovan populations has plausibly entailed significant
      changes also in other functional pathways than in the examined one. 

PMID- 24667835
TI  - Assessment of the impact of the 2003 and 2006 heat waves on cattle mortality in
      France.
AB  - OBJECTIVES: While several studies have highlighted and quantified human mortality
      during the major heat waves that struck Western Europe in 2003 and 2006, the
      impact on farm animals has been overlooked. The aim of this study was to assess
      the effect of these two events on cattle mortality in France, one of the most
      severely impacted countries. METHODS: Poisson regressions were used to model the
      national baseline for cattle mortality between 2004 and 2005 and predict the
      weekly number of expected deaths in 2003 and 2006 for the whole cattle population
      and by subpopulation based on age and type of production. Observed and estimated
      values were compared to identify and quantify excess mortality. The same approach
      was used at a departmental scale (a French department being an administrative and
      territorial division) to assess the spatio-temporal evolution of the mortality
      pattern. RESULTS: Overall, the models estimated relative excess mortality of 24%
      [95% confidence interval: 22-25%] for the two-week heat wave of 2003, and 12% [11
      14%] for the three-week heat wave of 2006. In 2003, most cattle subpopulations
      were impacted during the heat wave and some in the following weeks too. In 2006,
      cattle subpopulations were impacted for a limited time only, with no excess
      mortality at the beginning or after the heat wave. No marked differences in
      cattle mortality were found among the different subpopulations by age and type of
      production. The implications of these results for risk prevention are discussed.

PMID- 24667834
TI  - Lung function and incidence of chronic obstructive pulmonary disease after
      improved cooking fuels and kitchen ventilation: a 9-year prospective cohort
      study.
AB  - BACKGROUND: Biomass smoke is associated with the risk of chronic obstructive
      pulmonary disease (COPD), but few studies have elaborated approaches to reduce
      the risk of COPD from biomass burning. The purpose of this study was to determine
      whether improved cooking fuels and ventilation have effects on pulmonary function
      and the incidence of COPD. METHODS AND FINDINGS: A 9-y prospective cohort study
      was conducted among 996 eligible participants aged at least 40 y from November 1,
      2002, through November 30, 2011, in 12 villages in southern China. Interventions
      were implemented starting in 2002 to improve kitchen ventilation (by providing
      support and instruction for improving biomass stoves or installing exhaust fans)
      and to promote the use of clean fuels (i.e., biogas) instead of biomass for
      cooking (by providing support and instruction for installing household biogas
      digesters); questionnaire interviews and spirometry tests were performed in 2005,
      2008, and 2011. That the interventions improved air quality was confirmed via
      measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate
      matter with an aerodynamic diameter of 10 um or less) in a randomly selected
      subset of the participants' homes. Annual declines in lung function and COPD
      incidence were compared between those who took up one, both, or neither of the
      interventions. Use of clean fuels and improved ventilation were associated with a
      reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was
      reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in
      those who used clean fuels and improved ventilation, respectively, compared to
      those who took up neither intervention, after adjustment for confounders. The
      combined improvements of use of clean fuels and improved ventilation had the
      greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95%
      CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation,
      the greater the benefits in slowing the decline of FEV1 (p<0.05). The reduction
      in the risk of COPD was unequivocal after the fuel and ventilation improvements,
      with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.
      CONCLUSIONS: Replacing biomass with biogas for cooking and improving kitchen
      ventilation are associated with a reduced decline in FEV1 and risk of COPD. TRIAL
      REGISTRATION: Chinese Clinical Trial Register ChiCTR-OCH-12002398.

PMID- 24667837
TI  - Short-term effect of nutrient availability and rainfall distribution on biomass
      production and leaf nutrient content of savanna tree species.
AB  - Changes in land use may lead to increased soil nutrient levels in many ecosystems
      (e.g. due to intensification of agricultural fertilizer use). Plant species
      differ widely in their response to differences in soil nutrients, and for
      savannas it is uncertain how this nutrient enrichment will affect plant community
      dynamics. We set up a large controlled short-term experiment in a semi-arid
      savanna to test how water supply (even water supply vs. natural rainfall) and
      nutrient availability (no fertilisation vs. fertilisation) affects seedlings'
      above-ground biomass production and leaf-nutrient concentrations (N, P and K) of
      broad-leafed and fine-leafed tree species. Contrary to expectations, neither
      changes in water supply nor changes in soil nutrient level affected biomass
      production of the studied species. By contrast, leaf-nutrient concentration did
      change significantly. Under regular water supply, soil nutrient addition
      increased the leaf phosphorus concentration of both fine-leafed and broad-leafed
      species. However, under uneven water supply, leaf nitrogen and phosphorus
      concentration declined with soil nutrient supply, this effect being more
      accentuated in broad-leafed species. Leaf potassium concentration of broad-leafed
      species was lower when growing under constant water supply, especially when no
      NPK fertilizer was applied. We found that changes in environmental factors can
      affect leaf quality, indicating a potential interactive effect between land-use
      changes and environmental changes on savanna vegetation: under more uneven
      rainfall patterns within the growing season, leaf quality of tree seedlings for a
      number of species can change as a response to changes in nutrient levels, even if
      overall plant biomass does not change. Such changes might affect herbivore
      pressure on trees and thus savanna plant community dynamics. Although longer term
      experiments would be essential to test such potential effects of eutrophication
      via changes in leaf nutrient concentration, our findings provide important
      insights that can help guide management plans that aim to preserve savanna
      biodiversity. 

PMID- 24667836
TI  - Differentially expressed miRNAs in Ewing sarcoma compared to mesenchymal stem
      cells: low miR-31 expression with effects on proliferation and invasion.
AB  - Ewing sarcoma, the second most common bone tumor in children and young adults, is
      an aggressive malignancy with a strong potential to metastasize. Ewing sarcoma is
      characterised by translocations encoding fusion transcription factors with an
      EWSR1 transactivation domain fused to an ETS family DNA binding domain. microRNAs
      are post-transcriptional regulators of gene expression and aberrantly expressed
      microRNAs have been identified as tumor suppressors or oncogenes in most cancer
      types. To identify potential oncogenic and tumor suppressor microRNAs in Ewing
      sarcoma, we determined and compared the expression of 377 microRNAs in 40 Ewing
      sarcoma biopsies, 6 Ewing sarcoma cell lines and mesenchymal stem cells, the
      putative cellular origin of Ewing sarcoma, from 6 healthy donors. Of the 35
      differentially expressed microRNAs identified (fold change >4 and q<0.05), 19
      were higher and 16 lower expressed in Ewing sarcoma. In comparisons between Ewing
      sarcoma samples with EWS-FLI or EWS-ERG translocations, with differing
      dissemination characteristics and of primary samples and metastases no
      significantly differential expressed microRNAs were detected using various
      stringency criteria. For miR-31, the microRNA with lowest expression in
      comparison to mesenchymal stem cells, functional analyses were performed to
      determine its potential as a tumor suppressor in Ewing sarcoma. Two of four miR
      31 transfected Ewing sarcoma cell lines showed a significantly reduced
      proliferation (19% and 33% reduction) due to increased apoptosis in one and
      increased length of G1-phase in the other cell line. All three tested miR-31
      transfected Ewing sarcoma cell lines showed significantly reduced invasiveness
      (56% to 71% reduction). In summary, we identified 35 microRNAs differentially
      expressed in Ewing sarcoma and demonstrate that miR-31 affects proliferation and
      invasion of Ewing sarcoma cell lines in ex vivo assays. 

PMID- 24667839
TI  - Validation of the organizational culture assessment instrument.
AB  - Organizational culture is a commonly studied area in industrial/organizational
      psychology due to its important role in workplace behaviour, cognitions, and
      outcomes. Jung et al.'s [1] review of the psychometric properties of
      organizational culture measurement instruments noted many instruments have
      limited validation data despite frequent use in both theoretical and applied
      situations. The Organizational Culture Assessment Instrument (OCAI) has had
      conflicting data regarding its psychometric properties, particularly regarding
      its factor structure. Our study examined the factor structure and criterion
      validity of the OCAI using robust analysis methods on data gathered from 328
      (females = 226, males = 102) Australian employees. Confirmatory factor analysis
      supported a four factor structure of the OCAI for both ideal and current
      organizational culture perspectives. Current organizational culture data
      demonstrated expected reciprocally-opposed relationships between three of the
      four OCAI factors and the outcome variable of job satisfaction but ideal culture
      data did not, thus indicating possible weak criterion validity when the OCAI is
      used to assess ideal culture. Based on the mixed evidence regarding the measure's
      properties, further examination of the factor structure and broad validity of the
      measure is encouraged.

PMID- 24667838
TI  - Asexuality development among middle aged and older men.
AB  - OBJECTIVES: To assess erectile function in middle-aged and older men with
      asexuality status and further analyze their specific reasons for this condition.
      SUBJECTS AND METHODS: Men who had regular sexual intercourse attempts (sex
      frequency >= 1 time per month) were classified into mild erectile dysfunction
      (ED), moderate to severe ED and non-ED according to International Index of
      Erectile Function-5, and men having no sexual intercourse attempts for at least 6
      months were defined as having an asexuality status. The risk factors associated
      with ED were collected in a sample of 1,531 Chinese men aged 40 to 80 years, and
      the self-report reasons for asexuality were recorded in asexual cohort
      individually. Comparative analyses and multivariate regression models were
      conducted among these groups. RESULTS: The prevalence rates of ED and asexuality
      status were 49.9% and 37.2%. The asexuality status group had higher risk factors
      than the moderate to severe ED group in terms of old age (age >= 65, adjusted
      odds ratio (OR) 17.69 versus (Vs.) 7.19), diabetes (crude OR: 2.40 Vs. 2.36) and
      hypertension (crude OR: 1.78 Vs. 1.72). The specific reasons for the asexuality
      status were "erectile difficulty" (52.9%), "do not care about sexuality"
      (53.5%)", "no longer necessary to have sexuality at this age" (47.7%), "severe
      stress" (44.4%), "severe fatigue" (26.3%) and "masturbation" (26.9%).
      CONCLUSIONS: Men with an asexual status suffer from higher risk factors for ED
      than men with moderate to severe ED. The majority of this asexual status could be
      attributed to a full ED, although the reasons for this transient asexuality also
      involved sexual attitudes and interests, sexual partners and masturbation.

PMID- 24667840
TI  - Characterizing periodic messaging interventions across health behaviors and
      media: systematic review.
AB  - BACKGROUND: Periodic prompts serve as tools for health behavior interventions to
      encourage and maintain behavior changes. Past literature reviews have examined
      periodic messages targeting specific behaviors (smoking, physical activity, diet,
      etc) or media (telephone, email, face-to-face, newsletter, etc) and have found
      them to be effective in impacting health behavior in the short term. OBJECTIVE:
      Our goal was to review the literature related to periodic messaging and prompts
      in order to explore typical characteristics, assess the role of prompt timing,
      identify common theoretical models used, and identify characteristics associated
      with the effectiveness of periodic prompts. METHODS: Electronic searches of
      PubMed, PsycINFO, CINAHL, and Web of Science were conducted in October 2012 and
      May 2013. Database search terms included variant terms for periods, prompts,
      interventions, media, and health behaviors. RESULTS: Forty-two of the 55 included
      research articles found that prompts resulted in significant positive behavioral
      outcomes for participants. Prompts were delivered via text messages, email,
      mailed communications, and in a few instances via phone. Generally, the provision
      of feedback and specific strategies to accomplish behavior change appears to be
      important for the success of periodic prompts. Rationale for prompt timing was
      rarely provided, although some studies did organize message content around days
      of the week or times perceived to be high risk for particular behaviors. Smoking
      cessation interventions tended to be organized around quit date. Among studies
      using theoretical models to inform their interventions, the transtheoretical
      model was most common. CONCLUSIONS: Periodic messaging interventions yield
      positive results for short-term health behavior changes. Interventions including
      feedback and prompts that included strategies were more likely to report
      significantly positive outcomes. Work remains to better understand elements that
      make periodic prompts successful and whether they are effective in producing long
      term outcomes.

PMID- 24667841
TI  - Evidence for LINC1-SUN associations at the plant nuclear periphery.
AB  - Sad1/UNC84 (SUN) domain proteins are a highly conserved family of inner nuclear
      membrane localised proteins in eukaryotes. One of their main functions is as key
      components of nucleo-cytoskeletal bridging complexes, in which SUN proteins
      associate with nucleoskeletal elements. In metazoans these are the lamins, which
      form a supportive structural network termed the lamina. Plants lack sequence
      homologs of lamins but have a similar nucleoplasmic structural network to support
      the plant NE. Putative components of this plant lamina-like structure are Little
      Nuclei (LINC) proteins, which bear structural resemblance to lamins and fulfil
      similar functions. This work explores the associations between AtLINC1, AtSUN1
      and AtSUN2. AtLINC1 is recruited to the NE by SUN proteins and is immobilised
      therein. This recruitment and the immobile properties are likely due to AtSUN1/2
      AtLINC1 protein interactions occurring in planta. In addition, the SUN N-terminus
      appears to play an important role in mediating these interactions. The
      associations between AtLINC1 and plant SUN proteins are a first indicator of how
      the nucleoskeleton may be anchored to the nuclear membrane in plants. Building on
      the previous characterisation of Klarsicht/Anc1/Syne1 homology (KASH) like
      proteins in plants, this study advances the identification and characterisation
      of nucleo-cytoskeletal bridging complexes in plants. 

PMID- 24667842
TI  - Sulforaphane induces oxidative stress and death by p53-independent mechanism:
      implication of impaired glutathione recycling.
AB  - Sulforaphane (SFN) is a naturally-occurring isothiocyanate best known for its
      role as an indirect antioxidant. Notwithstanding, in different cancer cell lines,
      SFN may promote the accumulation of reactive oxygen species (ROS) and cause cell
      death e.g. by apoptosis. Osteosarcoma often becomes chemoresistant, and new
      molecular targets to prevent drug resistance are needed. Here, we aimed to
      determine the effect of SFN on ROS levels and to identify key biomarkers leading
      to ROS unbalance and apoptosis in the p53-null MG-63 osteosarcoma cell line. MG
      63 cells were exposed to SFN for up to 48 h. At 10 MUM concentration or higher,
      SFN decreased cell viability, increased the%early apoptotic cells and increased
      caspase 3 activity. At these higher doses, SFN increased ROS levels, which
      correlated with apoptotic endpoints and cell viability decline. In exposed cells,
      gene expression analysis revealed only partial induction of phase-2
      detoxification genes. More importantly, SFN inhibited ROS-scavenging enzymes and
      impaired glutathione recycling, as evidenced by inhibition of glutathione
      reductase (GR) activity and combined inhibition of glutathione peroxidase (GPx)
      gene expression and enzyme activity. In conclusion, SFN induced oxidative stress
      and apoptosis via a p53-independent mechanism. GPx expression and activity were
      found associated with ROS accumulation in MG-63 cells and are potential
      biomarkers for the efficacy of ROS-inducing agents e.g. as co-adjuvant drugs in
      osteosarcoma. 

PMID- 24667843
TI  - SCO-spondin derived peptide NX210 induces neuroprotection in vitro and promotes
      fiber regrowth and functional recovery after spinal cord injury.
AB  - In mammals, the limited regenerating potential of the central nervous system
      (CNS) in adults contrasts with the plasticity of the embryonic and perinatal
      periods. SCO (subcommissural organ)-spondin is a protein secreted early by the
      developing central nervous system, potentially involved in the development of
      commissural fibers. SCO-spondin stimulates neuronal differentiation and neurite
      growth in vitro. NX210 oligopeptide was designed from SCO-spondin's specific
      thrombospondin type 1 repeat (TSR) sequences that support the main neurogenic
      properties of the molecule. The objective of this work was to assess the
      neuroprotective and neuroregenerative properties of NX210 in vitro and in vivo
      for the treatment of spinal cord injury (SCI). In vitro studies were carried out
      on the B104 neuroblastoma cell line demonstrating neuroprotection by the
      resistance to oxidative damage using hydrogen peroxide and the measure of cell
      viability by metabolic activity. In vivo studies were performed in two rat models
      of SCI: (1) a model of aspiration of dorsal funiculi followed by the insertion of
      a collagen tube in situ to limit collateral sprouting; white matter regeneration
      was assessed using neurofilament immunostaining; (2) a rat spinal cord contusion
      model to assess functional recovery using BBB scale and reflex testing. We
      demonstrate for the first time that NX210 (a) provides neuroprotection to
      oxidative stress in the B104 neuroblastoma cells, (b) stimulates axonal regrowth
      in longitudinally oriented neofibers in the aspiration model of SCI and (c)
      significantly improves functional recovery in the contusive model of SCI. 

PMID- 24667844
TI  - Preparation of N-doped graphene by reduction of graphene oxide with mixed
      microbial system and its haemocompatibility.
AB  - A steady, effective and environment friendly method of introducing nitrogen into
      graphene is by microbial reduction of graphene oxide with mixed microorganisms
      from the anode chamber of microbial fuel cells (MFC). Using this method, N-doped
      graphene is easily obtained under mild conditions and by simple treatment
      processes, with the N/C ratio reaching 8.14%. Various characterizations
      demonstrate that the as-prepared N-doped graphene has excellent properties and is
      comparable with, and in some aspects, even better than, pristine graphene
      (containing only elemental C) prepared by chemical methods. The N-doped graphene
      (mainly substitution of C in the plane of the graphene sheet) with uniform
      distribution of N was haemocompatible, nontoxic, and water-dispersible, all of
      which are desirable properties for biomaterials and attributable to a synergetic
      metabolic effect of mixed microorganisms. 

PMID- 24667845
TI  - Heat stress induces apoptosis through transcription-independent p53-mediated
      mitochondrial pathways in human umbilical vein endothelial cell.
AB  - Cells apoptosis induced by intense heat stress is the prominent feature of heat
      related illness. However, little is known about the biological effects of heat
      stress on cells apoptosis. Herein, we presented evidence that intense heat stress
      could induce early apoptosis of HUVEC cells through activating mitochondrial
      pathway with changes in mitochondrial membrane potential(DeltaPsim), release of
      cytochrome c, and activation of caspase-9 and -3. We further revealed that p53
      played a crucial role in heat stress-induced early apoptosis, with p53 protein
      rapidly translocated into mitochondria. Using pifithrin-alpha(PFT), a p53's
      mitochondrial translocation inhibitor, we found that pretreated with PFT, heat
      stress induced mitochondrial p53 translocation was significantly suppressed,
      accompanied by a significant alleviation in the loss of DeltaPsim, cytochrome c
      release and caspase-9 activation. Furthermore, we also found that generation of
      reactive oxygen species (ROS) was a critical mediator in heat stress-induced
      apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat
      stress-induced p53's mitochondrial translocation, followed by the loss of
      DeltaPsim, cytochrome c release, caspase-9 activation and heat stress-mediated
      apoptosis. Conclusively, these findings indicate the contribution of the
      transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC
      cells induced by oxidative stress in response to intense heat stress. 

PMID- 24667847
TI  - A transcontinental challenge--a test of DNA barcode performance for 1,541 species
      of Canadian Noctuoidea (Lepidoptera).
AB  - This study provides a first, comprehensive, diagnostic use of DNA barcodes for
      the Canadian fauna of noctuoids or "owlet" moths (Lepidoptera: Noctuoidea) based
      on vouchered records for 1,541 species (99.1% species coverage), and more than
      30,000 sequences. When viewed from a Canada-wide perspective, DNA barcodes
      unambiguously discriminate 90% of the noctuoid species recognized through prior
      taxonomic study, and resolution reaches 95.6% when considered at a provincial
      scale. Barcode sharing is concentrated in certain lineages with 54% of the cases
      involving 1.8% of the genera. Deep intraspecific divergence exists in 7.7% of the
      species, but further studies are required to clarify whether these cases reflect
      an overlooked species complex or phylogeographic variation in a single species.
      Non-native species possess higher Nearest-Neighbour (NN) distances than native
      taxa, whereas generalist feeders have lower NN distances than those with more
      specialized feeding habits. We found high concordance between taxonomic names and
      sequence clusters delineated by the Barcode Index Number (BIN) system with 1,082
      species (70%) assigned to a unique BIN. The cases of discordance involve both BIN
      mergers and BIN splits with 38 species falling into both categories, most likely
      reflecting bidirectional introgression. One fifth of the species are involved in
      a BIN merger reflecting the presence of 158 species sharing their barcode
      sequence with at least one other taxon, and 189 species with low, but diagnostic
      COI divergence. A very few cases (13) involved species whose members fell into
      both categories. Most of the remaining 140 species show a split into two or three
      BINs per species, while Virbia ferruginosa was divided into 16. The overall
      results confirm that DNA barcodes are effective for the identification of
      Canadian noctuoids. This study also affirms that BINs are a strong proxy for
      species, providing a pathway for a rapid, accurate estimation of animal
      diversity. 

PMID- 24667846
TI  - Increased risk of benign prostate hyperplasia in sleep apnea patients: a
      nationwide population-based study.
AB  - BACKGROUND: Sleep apnea (SA) is a common sleep disorder characterized by chronic
      intermittent hypoxia (IH). Chronic IH induces systemic inflammatory processes,
      which can cause tissue damage and contribute to prostatic enlargement. The
      purpose of this study was to evaluate the association between benign prostate
      hyperplasia (BPH) and SA in a Taiwanese population. METHODS: The study population
      was identified from Taiwan's National Health Insurance Research Database (NHIRD)
      and contained 202 SA patients and 1010 control patients. The study cohort
      consisted of men aged >= 30 years who were newly diagnosed with SA between
      January 1997 and December 2005. Each patient was monitored for 5 years from the
      index date for the development of BPH. A Cox regression analysis was used to
      calculate the hazard ratios (HRs) for BPH in the SA and control patients.
      RESULTS: During the 5-year follow-up, 18 SA patients (8.9%) and 32 non-SA control
      patients (3.2%) developed BPH. The adjusted HR for BPH was 2.35-fold higher in
      the patients with SA than in the control patients (95% confidence interval (CI)
      1.28-4.29, P<.01). We further divided the SA patients into 4 age groups. After
      adjusting for potential confounding factors, the highest adjusted HR for BPH in
      the SA patients compared with the control patients was 5.59 (95% CI = 2.19-14.31,
      P<.001) in the patients aged between 51 and 65 years. CONCLUSION: Our study
      results indicate that patients with SA are associated with increased longitudinal
      risk of BPH development, and that the effects of SA on BPH development are age
      dependent.

PMID- 24667848
TI  - The logic of surveillance guidelines: an analysis of vaccine adverse event
      reports from an ontological perspective.
AB  - BACKGROUND: When increased rates of adverse events following immunization are
      detected, regulatory action can be taken by public health agencies. However to be
      interpreted reports of adverse events must be encoded in a consistent way.
      Regulatory agencies rely on guidelines to help determine the diagnosis of the
      adverse events. Manual application of these guidelines is expensive, time
      consuming, and open to logical errors. Representing these guidelines in a format
      amenable to automated processing can make this process more efficient. METHODS
      AND FINDINGS: Using the Brighton anaphylaxis case definition, we show that
      existing clinical guidelines used as standards in pharmacovigilance can be
      logically encoded using a formal representation such as the Adverse Event
      Reporting Ontology we developed. We validated the classification of vaccine
      adverse event reports using the ontology against existing rule-based systems and
      a manually curated subset of the Vaccine Adverse Event Reporting System. However,
      we encountered a number of critical issues in the formulation and application of
      the clinical guidelines. We report these issues and the steps being taken to
      address them in current surveillance systems, and in the terminological standards
      in use. CONCLUSIONS: By standardizing and improving the reporting process, we
      were able to automate diagnosis confirmation. By allowing medical experts to
      prioritize reports such a system can accelerate the identification of adverse
      reactions to vaccines and the response of regulatory agencies. This approach of
      combining ontology and semantic technologies can be used to improve other areas
      of vaccine adverse event reports analysis and should inform both the design of
      clinical guidelines and how they are used in the future. AVAILABILITY: Sufficient
      material to reproduce our results is available, including documentation,
      ontology, code and datasets, at http://purl.obolibrary.org/obo/aero.

PMID- 24667849
TI  - Smoking and body fat mass in relation to bone mineral density and hip fracture:
      the Hordaland Health Study.
AB  - Lower bone mineral density (BMD) in smokers may be attributable to lower body
      weight or fat mass, rather than to a direct effect of smoking. We analyzed the
      effects of smoking exposure, assessed by plasma cotinine, and body fat on BMD and
      the risk of subsequent hip fracture. In the community-based Hordaland Health
      Study (HUSK), 3003 participants 46-49 years and 2091 subjects 71-74 years were
      included. Cotinine was measured in plasma and information on health behaviors was
      obtained from self-administered questionnaires. BMD and total body soft tissue
      composition were measured by dual X-ray absorptiometry. Information on hip
      fracture was obtained from computerized records containing discharge diagnoses
      for hospitalizations between baseline examinations 1997-2000 through December
      31st, 2009. In the whole cohort, moderate and heavy smokers had stronger positive
      associations between fat mass and BMD compared to never smokers (differences in
      regression coefficient (95% CI) per % change in fat mass = 1.38 (0.24, 2.52) and
      1.29 (0.17, 2.4), respectively). In moderate and heavy smokers there was a
      nonlinear association between BMD and fat mass with a stronger positive
      association at low compared to high levels of fat mass (Davies segmented test,
      p<0.001). In elderly women and men, heavy smokers had an increased risk of hip
      fracture compared to never smokers (hazard ratio = 3.31, 95% CI: 2.05, 5.35;
      p<0.001). In heavy smokers there was a tendency of a lower risk of hip fracture
      with higher percentage of fat mass. The deleterious effect of smoking on bone
      health is stronger in lean smokers than in smokers with high fat mass.

PMID- 24667850
TI  - Induction of the calcineurin variant CnAbeta1 after myocardial infarction reduces
      post-infarction ventricular remodelling by promoting infarct vascularization.
AB  - AIMS: Ventricular remodelling following myocardial infarction progressively leads
      to loss of contractile capacity and heart failure. Although calcineurin promotes
      maladaptive cardiac hypertrophy, we recently showed that the calcineurin splicing
      variant, CnAbeta1, has beneficial effects on the infarcted heart. However,
      whether this variant limits necrosis or improves remodelling is still unknown,
      precluding translation to the clinical arena. Here, we explored the effects and
      therapeutic potential of CnAbeta1 overexpression post-infarction. METHODS AND
      RESULTS: Double transgenic mice with inducible cardiomyocyte-specific
      overexpression of CnAbeta1 underwent left coronary artery ligation followed by
      reperfusion. Echocardiographic analysis showed depressed cardiac function in all
      infarcted mice 3 days post-infarction. Induction of CnAbeta1 overexpression 1
      week after infarction improved function and reduced ventricular dilatation.
      CnAbeta1-overexpressing mice showed shorter, thicker scars, and reduced infarct
      expansion, accompanied by reduced myocardial remodelling. CnAbeta1 induced
      vascular endothelial growth factor (VEGF) expression in cardiomyocytes, which
      resulted in increased infarct vascularization. This paracrine angiogenic effect
      of CnAbeta1 was mediated by activation of the Akt/mammalian target of rapamycin
      pathway and VEGF. CONCLUSIONS: Our results indicate that CnAbeta1 exerts
      beneficial effects on the infarcted heart by promoting infarct vascularization
      and preventing infarct expansion. These findings emphasize the translational
      potential of CnAbeta1 for gene-based therapies.

PMID- 24667851
TI  - Central blockade of TLR4 improves cardiac function and attenuates myocardial
      inflammation in angiotensin II-induced hypertension.
AB  - AIMS: Understanding the novel signalling pathways involved in the pathogenesis of
      hypertension is vital for the development of effective therapeutic strategies.
      Recent evidence suggests a role for Toll-like receptor (TLR) 4 in the development
      of cardiovascular diseases. Although brain has been implicated in the
      pathogenesis of hypertension, the role of brain TLR4 in hypertension is largely
      unexplored. Therefore, we investigated the role of brain TLR4 in angiotensin
      (Ang) II-induced hypertension and whether central TLR4 blockade has
      cardioprotective effects in hypertension. METHODS AND RESULTS: Hypertension was
      induced in male Sprague-Dawley rats by delivering AngII for 14 days. The rats
      were administered either specific TLR4 blocker, viral inhibitory peptide (VIPER),
      or control peptide, intracerebroventricularly. Blood pressure, and cardiac
      hypertrophy and function, was evaluated by radiotelemetry and echocardiography,
      respectively. Blood and paraventricular nucleus were collected for measurement of
      plasma norepinephrine (NE), tumour necrosis factor-alpha (TNF-alpha), interleukin
      (IL)-1beta, and TLR4 expression, respectively. Heart was analysed for TNF-alpha,
      IL-1beta, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B
      (NFkappaB), and renin-angiotensin system (RAS) components. Hypertensive rats had
      dramatically increased TLR4 expression compared with normotensive rats. Central
      blockade of TLR4 delayed progression of hypertension and improved cardiac
      hypertrophy and function in hypertensive rats. TLR4 blockade significantly
      reduced myocardial TNF-alpha, IL-1beta, iNOS levels, NFkappaB activity, and
      altered RAS components in hypertensive rats. These results were associated with
      reduced circulating NE levels in VIPER-treated hypertensive rats. CONCLUSION:
      These results provide mechanistic evidence that AngII-induced hypertensive
      effects are mediated, at least in part, by brain TLR4, and that brain TLR4
      blockade attenuates AngII-induced hypertensive response, possibly via down
      regulation of myocardial inflammatory molecules and sympathetic activity.

PMID- 24667852
TI  - A phosphine-mediated reaction of cyclic 1,2-diones and 3-alkyl allenoates: an
      efficient protocol for benzannulation applicable to the synthesis of polycyclic
      aromatic hydrocarbons.
AB  - A facile one-pot benzannulation strategy involving phosphine-3-alkyl allenoate
      zwitterions and cyclic 1,2-diones is described. The strategy is effectively
      utilized in the synthesis of fluoranthenes and benzo[a]aceanthrylenes with
      impressive photophysical properties. This is the first report on an
      intermolecular benzannulation using a 3-alkyl allenoate as a four carbon synthon.

PMID- 24667853
TI  - Modulation of the electronic and spectroscopic properties of Zn(II)
      phthalocyanines by their substitution pattern.
AB  - Four isomerically pure octasubstituted zinc phthalocyanines with variations in
      the attachment atom and positions of the substituents were selected for a
      systematic investigation of the effect of the substitution pattern on their
      electronic and spectroscopic properties. Effects which were investigated are the
      position, the electron donating and withdrawing properties, and the donating
      force of the substituent. The results are discussed and interpreted based on
      theoretical and experimental determination of the orbital levels. This work
      allows us to highlight which substitution patterns are the most suitable
      considering different common applications of phthalocyanines. 

PMID- 24667854
TI  - Mercury elimination rates for adult northern pike Esox lucius: evidence for a sex
      effect.
AB  - We examined the effect of sex on mercury elimination in fish by monitoring
      isotope-enriched mercury concentrations in the muscle tissue of three adult
      female and three adult male northern pike Esox lucius, which had accumulated the
      isotope-enriched mercury via a whole-lake manipulation and were subsequently
      moved to a clean lake. Mercury elimination rates for female and male northern
      pike were estimated to be 0.00034 and 0.00073 day(-1), respectively. Thus, males
      were capable of eliminating mercury at more than double the rate than that of
      females. To the best of our knowledge, our study represents the first
      documentation of mercury elimination rates varying between the sexes of fish.
      This sex difference in elimination rates should be taken into account when
      comparing mercury accumulation between the sexes of fish from the same
      population. Further, our findings should eventually lead to an improved
      understanding of mechanisms responsible for mercury elimination in vertebrates.

PMID- 24667855
TI  - Does the clam Ensis siliqua provide useful information about contamination by
      polychlorinated biphenyls and organochlorine pesticides beyond that of mussel
      Mytilus galloprovincialis?
AB  - Several polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs)
      investigated in soft tissues of the frequently monitored Mytilus
      galloprovincialis were compared to those of Ensis siliqua, a highly dispersed and
      economically important bivalve species, though rarely investigated. Overall PCBs
      had higher concentrations than OCPs in both species with a prevalence of tri-
      tetra-and penta-chlorinated biphenyls in E. siliqua and a prevalence of hexa-
      hepta and octa-chlorinated biphenyls in M. galloprovincialis. E. siliqua emerges
      as a suitable complement to mussels for monitoring PCBs and OCPs pollution.

PMID- 24667856
TI  - Correlations between elements in the fur of wild animals.
AB  - There is little data on the elemental composition of wild animals fur. In the
      paper, an attempt has been made to evaluate the concentration of elements in the
      fur of roe deer, wild boar and hare. The contents of following elements: calcium
      (Ca), magnesium (Mg), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), lead
      (Pb), cadmium (Cd), aluminium (Al), chromium (Cr), nickel (Ni) were determined by
      atomic absorption spectrometry method. Their content was in the range 0.01 (Cd)
      to 1,519 (Ca) MUg/g. Correlations between the content of Mn, Al, Ca, Pb, Cr, Ni
      in the fur of animals, liver and muscle tissues were found. Thus it can be
      assumed that the fur of wild animals can provide an information on the
      bioavailability of elements and environmental exposure and can be considered as
      an useful biomarker in animals and environmental studies, although research on
      this subject should be continued. 

PMID- 24667857
TI  - Measures of body shape and adiposity as related to incidence of age-related eye
      diseases: observations from the Beaver Dam Eye Study.
AB  - PURPOSE: To examine the effect of obesity on the incidence of age-related eye
      disease. METHODS: Participants of the Beaver Dam Eye Study were examined every 5
      years over a 20-year period (1988-1990 through 2008-2010). Lens and fundus
      photographs were used to evaluate presence and severity of cataract and macular
      degeneration. Height and weight were measured at all examinations. Waist and hip
      circumference were measured at all examinations beginning at the first follow-up
      (1993-1995). Models of ocular outcomes over 15 years were stratified by sex and
      smoking status. RESULTS: Overall, 2641 participants contributed 5567 person
      visits to 15-year incidence analysis. Female nonsmokers had increased risk of
      late AMD associated with higher body mass index (BMI; hazard ratio [HR] per 2.5
      kg/m(2) 1.31, 95% confidence interval [CI] 1.15-1.50, P < 0.001), waist to hip
      ratio (HR per 0.1 cm/cm 1.95, 95% CI 1.33-2.86, P < 0.001), waist circumference
      (HR per 5 cm 1.21, 95% CI 1.10-1.34, P < 0.001), and waist to height ratio (HR
      per 0.1 cm/cm 1.74, 95% CI 1.31-2.31, P < 0.001). Increased BMI was also
      associated with early AMD in female nonsmokers (HR 1.10, 95% CI 1.02-1.19, P =
      0.02). CONCLUSIONS: Female nonsmokers had risk of late AMD associated with
      increasing measures of greater obesity and increased risk of early AMD associated
      with greater BMI.

PMID- 24667858
TI  - Carbonic anhydrase inhibitors in corneal endothelial transport.
AB  - PURPOSE: Carbonic anhydrases play a central buffering role in current models of
      fluid transport in corneal endothelium, but in humans, clinical use of carbonic
      anhydrase inhibitors (CAIs) for the management of glaucoma does not cause corneal
      swelling. This study compares species differences in response to CAIs in human
      versus bovine corneal endothelial transport. METHODS: Short-circuit current (Isc)
      measurements were performed on bovine and human corneal endothelium under
      identical conditions. The effects of four CAIs (acetazolamide, brinzolamide,
      dorzolamide, and ethoxzolamide) were measured. Endothelial expression of carbonic
      anhydrase II and IV was evaluated by immunofluorescence microscopy. Functional
      presence of carbonic anhydrase activity was determined using the Hansson's cobalt
      sulfide histochemical method. RESULTS: All four CAIs decreased bovine Isc (%
      change in Isc: acetazolamide, -21.0 +/- 9.5, n = 8; brinzolamide, -35.5 +/- 13.5,
      n = 9; dorzolamide, -33.6 +/- 7.2, n = 8; ethoxzolamide, -35.3 +/- 12.9, n = 8).
      That decrease was not present in humans (% change in Isc: acetazolamide, 16.2 +/-
      20.1, n = 3; brinzolamide, 6.7 +/- 13.9, n = 3; dorzolamide, 8.0 +/- 20.4, n = 3;
      ethoxzolamide, -4.8 +/- 10.3, n = 2). Despite no functional effect of CAIs on
      Isc, both carbonic anhydrase II and IV were present in human corneal endothelium
      by immunofluorescence microscopy. Histochemical analysis of human corneal
      endothelium revealed functionally active carbonic anhydrase activity inhibited by
      brinzolamide. CONCLUSIONS: Carbonic anhydrase facilitates ion transport impacting
      the corneal endothelial Isc in bovine but not human corneal endothelium, despite
      its presence and functional activity in human tissue. This finding supports the
      clinical observation of no corneal swelling in humans administered CAIs and
      suggests that alternative ion transport mechanisms may be operational in corneal
      endothelium of different species.

PMID- 24667859
TI  - Structural modifications and tissue response after standard epi-off and
      iontophoretic corneal crosslinking with different irradiation procedures.
AB  - PURPOSE: The aim of this study is to investigate modifications in human cadaver
      corneas after different crosslinking procedures, including standard epi-off
      treatment, iontophoresis imbibition, and different exposure to ultraviolet A
      (UVA) sources (30 minutes at 3 mW and 9 minutes at 10 mW). METHODS: A total of 12
      human cadaver corneas was examined and divided as follows: 3 served as control
      (group 1), 3 were treated with a standard epi-off procedure (group 2), 6
      underwent iontophoresis imbibition for 5 minutes, and then 3 were irradiated for
      30 minutes with 3 mW UVA (group 3), and 3 for 9 minutes at 10 mW UVA (group 4).
      Deformation amplitude index was measured before and after the corneas underwent
      treatment. After treatment, corneas were prepared for hematoxylin-eosin and
      immunohistochemistry evaluation. The expression of TUNEL, matrix
      metalloproteinase-1 (MMP-1), collagen type I, and CD34 was investigate in all
      samples. RESULTS: The deformation amplitude index decreased in all groups, in
      particular in group 4, indicating an improvement of corneal biomechanical
      properties. Immunohistochemical staining showed a significant stromal alteration
      in group 2, mild damage in group 3, and no modifications in corneal morphology in
      group 4. The TUNEL (P < 0.001) and MMP-1 (P = 0.002) positivity was more evident
      in group 4. Collagen type I positivity significantly increased in groups 3 (P =
      0.002) and 4 (P = 0.002). The CD34 expression was more evident in groups 2 (P =
      0.003) and 3 (P = 0.003). CONCLUSIONS: Iontophoresis imbibition followed by UVA
      irradiation for 9 minutes at 10 mW determined less tissue damage and better
      stromal remodeling.

PMID- 24667860
TI  - Evaluating in vivo delivery of riboflavin with coulomb-controlled iontophoresis
      for corneal collagen cross-linking: a pilot study.
AB  - PURPOSE: To evaluate the efficacy of coulomb-controlled iontophoresis (CCI) for
      delivery of riboflavin prior to corneal collagen cross-linking (CXL). METHODS:
      The eyes of 20 8-week-old Lewis rats, subject to epithelium-ON (epi-ON, n = 20
      eyes) or epithelium-OFF (epi-OFF, n = 20 eyes) conditions, were used to evaluate
      the in vivo delivery of two riboflavin solutions: 0.1% riboflavin-20% dextran
      T500 solution (riboflavin-dextran) and 0.1% riboflavin 5'-phosphate (riboflavin
      phosphate). After systemic intramuscular anesthesia, 0.25 mL of the
      photosensitizing agent was delivered by either instillation or CCI (2.11 mA/cm(2)
      for 4 or 10 minutes) into either epithelial condition. The CCI probe on the eye
      without current served as control. Confocal microscopy of flat-mounted corneas
      was used to analyze intracorneal penetration and fluorometry was used to quantify
      riboflavin in the aqueous within 30 minutes of treatment. RESULTS: Instillation
      and CCI allowed for uniform delivery of riboflavin-dextran throughout the stroma
      after epithelial debridement. Transepithelial delivery of riboflavin-dextran was
      not efficacious. Riboflavin-phosphate was successfully delivered in both
      epithelium conditions. Complete saturation of the cornea was achieved using CCI
      after removing the epithelium, the epi-ON case allowed for limited diffusion.
      Increasing the time from 4 to 10 minutes greatly increased the amount of
      riboflavin detected in the cornea and aqueous humor. CONCLUSIONS: Coulomb
      controlled iontophoresis is an effective technique for transepithelial delivery
      of riboflavin-phosphate into the cornea. This drug delivery method would allow
      clinicians to significantly shorten the time required for the CXL procedure, with
      or without epithelial debridement. Whether efficient crosslinking can be achieved
      through an intact epithelium remains to be demonstrated.

PMID- 24667861
TI  - Robust mouse pattern electroretinograms derived simultaneously from each eye
      using a common snout electrode.
AB  - PURPOSE: We recorded pattern electroretinograms (PERGs) simultaneously from each
      eye in mice using binocular stimulation and a common noncorneal electrode.
      METHODS: The PERG was derived simultaneously from each eye in 71
      ketamine/xylazine anesthetized mice (C57BL/6J, 4 months old) from subcutaneous
      needles (active, snout; reference, back of the head; ground, root of the tail) in
      response to contrast-reversal of gratings (0.05 cycles/deg, >95% contrast)
      generated on two custom-made light-emitting diode (LED) tablets alternating at
      slight different frequencies (OD, 0.984 Hz; OS, 0.992 Hz). Independent PERG
      signals from each eye were retrieved using one channel continuous acquisition and
      phase-locking average (OD, 369 epochs of 492 ms; OS, 372 epochs of 496 ms). The
      PERG was the average of three consecutive repetitions. RESULTS: Binocular snout
      PERGs had high amplitude (mean, 25.3 MUV, SD 6.6) and no measurable interocular
      cross-talk. Responses were reliable (test-retest variability within-session, 14%,
      SD 7; between sessions, 25%, SD 9; interocular asymmetry within-session, 9%, SD
      7; between sessions, 13%, SD 5). Retinal ganglion cells (RGCs) were the main
      source of the binocular snout PERG, as optic nerve crush in three mice abolished
      the signal. CONCLUSIONS: The PERG, a sensitive measure of RGC function, is used
      increasingly in mouse models of glaucoma and optic nerve disease. Compared to
      current methods, the binocular snout PERG represents a substantial improvement in
      terms of simplicity and speed. It also overcomes limitations of corneal
      electrodes that interfere with invasive procedures of the eye and facilitates
      experiments based on comparison between the responses of the two eyes.

PMID- 24667862
TI  - Quantification of the image obtained with a wide-field scanning ophthalmoscope.
AB  - PURPOSE: To quantify the angle of view, the magnification, and the quality of
      images acquired with an Optos 200Tx. METHODS: We obtained fundus images of a
      model eye with the Optos 200Tx and recorded the maximal scale imaged in each
      direction. We measured the length of the scale bar and the interval of the scale
      bars at each angle and calculated the magnification. We also measured the
      contrast between scale bars and the intervals between scale bars. RESULTS: The
      fundus image obtained with the Optos 200Tx covered 96, 101, 76, and 102 degrees 
      in the up, right, down, and left directions, respectively. Quantitative
      measurement showed that the overall image is stretched 1.12-fold in the
      horizontal direction with respect to the vertical. The magnification with respect
      to the posterior pole increased quadratically in all directions, most steeply in
      the vertical direction, reaching 2.0 * 1.5 in the most extreme case. The image
      quality was best in the left part and was worse in the inferior and superior
      parts. CONCLUSIONS: The Optos 200Tx can obtain an image duplicated, with an
      angular range of approximately 200 degrees  horizontally and 170 degrees 
      vertically, with greatest limitation in the inferior direction. It should be
      noted that the most peripheral part of the image is significantly and unequally
      magnified. In addition, the contrast is not the same at all positions. The
      present data would serve as a guide to correct the peripheral magnification in
      future studies.

PMID- 24667863
TI  - Overexpression of herpes simplex virus glycoprotein K (gK) alters expression of
      HSV receptors in ocularly-infected mice.
AB  - PURPOSE: We have shown previously that HSV-1 glycoprotein K (gK) exacerbates
      corneal scarring (CS) in mice and rabbits. Here, we investigated the relative
      impact of gK overexpression on host responses during primary corneal infection
      and latency in trigeminal ganglia (TG) of infected mice. METHODS: Mice were
      infected ocularly with HSV-gK(3) (expressing two extra copies of gK replacing
      latency associated transcript [LAT]), HSV-gK(3) revertant (HSV-gK(3)R), or wild
      type HSV-1 strain McKrae. Individual corneas on day 5 post infection (PI) and TG
      on day 28 PI were isolated and used for detection of gB DNA in the TG, HSV-1
      receptors in the cornea and TG, and inflammatory infiltrates in TG. RESULTS:
      During primary HSV-1 infection, gK overexpression resulted in altered expression
      of herpesvirus entry mediator (HVEM), 3-O-sulfated heparin sulfate (3-OS-HS),
      paired immunoglobulin-like type 2 receptor-alpha (PILR-alpha), nectin-1, and
      nectin-2 in cornea of BALB/c, but not C57BL/6 mice. However, gK overexpression
      did have an effect on 3-OS-HS, PILR-alpha, nectin-1, and nectin-2 expression (but
      not HVEM expression) in TG of C57BL/6 mice during latency. These differences did
      not affect the level of latency, but instead were correlated with the presence of
      CS. The presence of LAT increased HVEM expression and this effect was enhanced
      further by the presence of CS in latently-infected mice. Finally, the presence of
      LAT, but not overexpression of gK, affected CD4, CD8, TNF-alpha, Tim-3, PD-1, IL
      21, IL-2, and IFN-gamma expression in TG. CONCLUSIONS: We demonstrate a novel
      link between gK exacerbation of CS and HSV-1 receptors, suggesting a gK-induced
      molecular route for the pathogenesis as well as selective advantage of these
      entry routes for the pathogen during latency-reactivation cycle.

PMID- 24667864
TI  - TGF-beta1 stimulates human Tenon's capsule fibroblast proliferation by miR-200b
      and its targeting of p27/kip1 and RND3.
AB  - PURPOSE: To evaluate the role of miR-200b expression in the proliferation of
      human Tenon's capsule fibroblasts (HTFs) induced by transforming growth factor
      beta 1 (TGF-beta1). METHODS: Human Tenon's capsule fibroblasts were treated with
      various doses of TGF-beta1 for 24 hours. Cell proliferation was quantified by the
      cell counting kit-8 (cck-8) assay, cell cycle analysis, 5-ethynyl-2-deoxyuridine
      (EdU) assay, and analysis of cyclin E, cyclin D1, and proliferating cell nuclear
      antigen (PCNA) expression. MicroRNA-200b (miR-200b) was detected by quantitative
      reverse-transcriptase polymerase chain reaction (qRT-PCR), and its potential
      target genes were validated by the luciferase assay and Western blot analysis.
      The effect of miR-200b on the proliferation of HTFs was analyzed using both
      miR200b-mimic and inhibitor-transfected HTFs and confirmed in p27/kip1 and RND3
      (the target of miR-200b) knockdown cells. RESULTS: The proliferation of the TGF
      beta1-treated HTFs increased significantly in a dose- and time-dependent manner.
      Treatment with 5 ng/mL TGF-beta1 caused an upregulation of miR-200b. The
      luciferase assay identified p27/kip1 and RND3 as target genes for miRNA-200b,
      which was confirmed by the expression of p27/kip1 and RND3 and their downstream
      products (cyclinE and cyclinD1) in the TGF-beta1-treated cells. Transforming
      growth factor-beta1 and miR-200b mimics enhanced the proliferation of HTFs;
      suppressed the expression of p27/kip1 and RND3; and subsequently stimulated the
      expression of cyclinE, cyclinD1, and PCNA. The miR-200b inhibitor attenuated the
      effects of TGF-beta1 on HTFs. Furthermore, knockdown of p27/kip1 and RND3
      resulted in an increase in cell proliferation and expression of the proliferation
      related genes. CONCLUSIONS: MicroRNA-200b acts as a stimulant for the
      proliferation of HTFs by targeting p27/kip1 and RND3.

PMID- 24667865
TI  - Expanded neurologic assessment in pediatric acute liver failure: an important
      initial step.

PMID- 24667866
TI  - Growth and fatty acid profiles of VLBW infants receiving a multicomponent lipid
      emulsion from birth.
AB  - OBJECTIVES: Very-low-birth-weight (VLBW) infants are dependent on parenteral
      nutrition after birth. A parenteral lipid emulsion with a multicomponent
      composition may improve growth and neurodevelopment and may prevent liver injury,
      which is often observed in association with long-term parenteral nutrition with
      pure soybean oil. Our aim was to evaluate the safety and efficacy of a
      multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain
      triacylglycerol, 25% olive oil, and 15% fish oil compared with a conventional
      pure soybean oil emulsion in VLBW infants. METHODS: We conducted a double-blind
      randomized controlled trial in VLBW infants randomized to parenteral nutrition
      with the multicomponent (study group) or pure soybean oil emulsion (control
      group) from birth at a dose of 2 to 3 g . kg(-1) . day(-1) until the infants were
      receiving full enteral nutrition. We assessed efficacy by growth rates and
      measuring plasma fatty acid profiles (representative subset). Safety was
      evaluated by assessing hematologic and biochemical parameters, potentially
      harmful phytosterol concentrations (same subset), and clinical neonatal outcome
      parameters. RESULTS: Ninety-six infants were included (subsets n = 21). The
      multicomponent emulsion was associated with higher weight and head circumference
      z scores during admission. Plasma eicosapentaenoic acid and docosahexaenoic acid
      concentrations were higher in the study group. The hematological, biochemical,
      and neonatal outcomes were not different between groups, whereas the plasma
      concentrations of phytosterols were higher in the control group. CONCLUSIONS: The
      multicomponent lipid emulsion was well tolerated and associated with improved
      growth and higher plasma fatty acid profiles in VLBW infants in comparison with
      the pure soybean oil emulsion.

PMID- 24667867
TI  - Fructose intolerance/malabsorption and recurrent abdominal pain in children.
AB  - OBJECTIVES: The purpose of the present study was to ascertain whether pediatric
      patients with chronic abdominal pain had concurrent fructose intolerance as
      determined by a standardized dose breath hydrogen test (BHT), and whether
      symptoms would improve with a low-fructose diet. METHODS: The fructose BHT test
      was administered to patients evaluated in clinic with unexplained chronic
      abdominal pain alone or associated with constipation, gas or bloating, and/or
      diarrhea. The patients were given a standard dose of 1 g/kg fructose to maximum
      of 25 g. Hydrogen and methane were measured at 8 time points. The test was
      presumed positive if breath hydrogen exceeded 20 ppm above baseline. If positive,
      patients were given a dietitian-prescribed low-fructose diet. RESULTS: A total of
      222 patients were part of the study. Ages ranged from 2 to 19 years with a mean
      of 10.5. BHT for fructose was performed in all of the patients and it was
      positive for fructose intolerance in 121 of 222 patients (54.5%). A total of 101
      of 222 (45.5%) patients had negative BHT for fructose intolerance. All BHT
      positive patients had a nutrition consult with a registered dietitian and were
      placed on a low-fructose diet. Using a standard pain scale for children, 93 of
      121 patients (76.9%) reported resolution of symptoms on a low-fructose diet (P <
      0.0001). Furthermore, 55 of 101 patients (54.4%) with negative BHT for fructose
      reported resolution of symptoms without a low-fructose diet (P = 0.37).
      CONCLUSIONS: Fructose intolerance/malabsorption is common in children with
      recurrent/functional abdominal pain and a low-fructose diet is an effective
      treatment.

PMID- 24667868
TI  - Evaluation of serum lipase as predictor of severity of acute pancreatitis in
      children.

PMID- 24667871
TI  - Aerobic oxidation catalysis with stable radicals.
AB  - Selective oxidation reactions are challenging when carried out on an industrial
      scale. Many traditional methods are undesirable from an environmental or safety
      point of view. There is a need to develop sustainable catalytic approaches that
      use molecular oxygen as the terminal oxidant. This review will discuss the use of
      stable radicals (primarily nitroxyl radicals) in aerobic oxidation catalysis. We
      will discuss the important advances that have occurred in recent years,
      highlighting the catalytic performance, mechanistic insights and the expanding
      synthetic utility of these catalytic systems. 

PMID- 24667870
TI  - Interfacial assembly of ZnO quantum dots into giant supramolecular architectures.
AB  - Para-aminobenzoic acid (PABA) stabilised zinc oxide (ZnO) quantum dots (QDs) have
      been synthesised by refluxing zinc acetate dihydrate in methanol under alkaline
      condition and re-dispersed into water by centrifugation. Aqueous dispersion of
      PABA-stabilised ZnO QDs was taken with seven different organic solvents in test
      tubes and subjected to diazo reaction under specified conditions. It was seen
      that the quantum dots assembled into diverse superstructures depending on the
      nature of the immiscible solvent at the aqueous-organic interface. The assemblies
      so obtained have been characterised by energy dispersive X-ray (EDX) analysis,
      Fourier transform infrared (FTIR), fluorescence and Raman spectroscopy, X-ray
      diffraction (XRD) and thermogravimetric analysis (TGA), optical, fluorescence and
      scanning electron microscopic (SEM) images. It has been observed that the ensuing
      supramolecular assemblies exhibit significant electrical conductivity and
      photoluminescence properties. 

PMID- 24667872
TI  - Granulocytes affect double-strand break repair assays in primary human
      lymphocytes.
AB  - Patients who develop therapy-related myelodysplasia/acute myeloid leukemia after
      autologous-hematopoietic stem cell (aHCT) transplant show lower expression levels
      of DNA repair genes in their pre-aHCT CD34+ cells. To investigate whether this
      leads to functional differences in DNA repair abilities measurable in patients,
      we adapted two plasmid-based host-cell reactivation assays for use in primary
      lymphocytes. Prior to applying these assays to patients who underwent aHCT, we
      wanted first to verify whether sample preparation affected repair measurements,
      as patient samples were simply depleted of erythrocytes (with hetastarch) prior
      to freezing, which is not the classical way to prepare lymphocytes prior to DNA
      repair experiments (with a density gradient). We show here that lymphocytes from
      healthy donors freshly prepared with hetastarch show systematically a higher
      level of double-strand break repair as compared to when prepared with a density
      gradient, but that most of this difference disappears after samples were frozen.
      Several observations points to granulocytes as the source for this effect of
      sample preparation on repair: 1) removal of granulocytes makes the effect
      disappear, 2) DSB repair measurements for the same individual correlate to the
      percentage of granulocytes in the sample and 3) nucleofection in presence of
      granulocytes increases the level of reactive oxygen species (ROS) in neighboring
      lymphocytes in a dose-dependent manner (R2 of 0.95). These results indicate that
      co-purified granulocytes, possibly through the release of ROS at time of
      transfection, can lead to an enhanced repair in lymphocytes that obfuscates any
      evaluation of inter individual differences in repair as measured by host-cell
      reactivation. As a result, hetastarch-prepared samples are likely unsuitable for
      the assessment of DSB repair in primary cells with that type of assay.
      Granulocyte contamination that exists after a density gradient preparation,
      although much more limited, could have similar effects, but might be circumvented
      by freezing cells prior to analysis. 

PMID- 24667874
TI  - Doping strategies to control A-centres in silicon: insights from hybrid density
      functional theory.
AB  - Hybrid density functional theory is used to gain insights into the interaction of
      intrinsic vacancies (V) and oxygen-vacancy pairs (VO, known as A-centres) with
      the dopants (D) germanium (Ge), tin (Sn), and lead (Pb) in silicon (Si). We
      determine the structures as well as binding and formation energies of the DVO and
      DV complexes. The results are discussed in terms of the density of states and in
      view of the potential of isovalent doping to control A-centres in Si. We argue
      that doping with Sn is the most efficient isovalent doping strategy to suppress A
      centres by the formation of SnVO complexes, as these are charge neutral and
      strongly bound. 

PMID- 24667875
TI  - Timing of tracheostomy in critically ill patients: a meta-analysis.
AB  - OBJECTIVE: To compare important outcomes between early tracheostomy (ET) and late
      tracheostomy (LT) or prolonged intubation (PI) for critically ill patients
      receiving long-term ventilation during their treatment. METHOD: We performed
      computerized searches for relevant articles on PubMed, EMBASE, and the Cochrane
      register of controlled trials (up to July 2013). We contacted international
      experts and manufacturers. We included in the study randomized controlled trials
      (RCTs) that compared ET (performed within 10 days after initiation of laryngeal
      intubation) and LT (after 10 days of laryngeal intubation) or PI in critically
      ill adult patients admitted to intensive care units (ICUs). Two investigators
      evaluated the articles; divergent opinions were resolved by consensus. RESULTS: A
      meta-analysis was evaluated from nine randomized clinical trials with 2,072
      participants. Compared to LT/PI, ET did not significantly reduce short-term
      mortality [relative risks (RR) = 0.91; 95% confidence intervals (CIs) = 0.81
      1.03; p = 0.14] or long-term mortality (RR = 0.90; 95% CI = 0.76-1.08; p = 0.27).
      Additionally, ET was not associated with a markedly reduced length of ICU stay
      [weighted mean difference (WMD) = -4.41 days; 95% CI = -13.44-4.63 days; p =
      0.34], ventilator-associated pneumonia (VAP) (RR = 0.88; 95% CI = 0.71-1.10; p =
      0.27) or duration of mechanical ventilation (MV) (WMD = - 2.91 days; 95% CI = 
      7.21-1.40 days; p = 0.19). CONCLUSION: Among the patients requiring prolonged MV,
      ET showed no significant difference in clinical outcomes compared to that of the
      LT/PI group. But more rigorously designed and adequately powered RCTs are
      required to confirm it in future.

PMID- 24667877
TI  - Pudendal nerve 3-dimensional illustration gives insight into surgical approaches.
AB  - The pudendal nerve is located topographically in areas in which plastic surgeon
      reconstruct the penis, the vagina, the perineum, and the rectum. This nerve is at
      risk for either compression or direct injury with neuroma formation from
      obstetrical, urogynecologic, and rectal surgery as well as pelvic fracture and
      blunt trauma. The purpose of this study was to create a 3-dimensional
      representation based on magnetic resonance imaging of the pelvis supplemented
      with new anatomic dissections in men and women to delineate the location of the
      pudendal nerve and its branches, providing educational information both for
      surgical intervention and patient education. The results of this study
      demonstrated that most often there are at least 2, not 1, "pudendal nerves
      trunks" as they leave the pelvis to transverse the sacrotuberous ligament, and
      that there are most often 2, not 1, exit(s) from Alcock canal, one for the dorsal
      branch and one for the perineal branch of the pudendal nerve. 

PMID- 24667876
TI  - Risk factors for adherence failure in HIV-infected sub-Saharan migrants living in
      France and travelling back to their native country.

PMID- 24667878
TI  - The value of color duplex imaging for planning and performing a free
      anterolateral thigh perforator flap.
AB  - INTRODUCTION: The free anterolateral thigh (ALT) flap has been used successfully
      for various soft tissue reconstructions. However, the drawback of this flap has
      been the difficulty associated with finding consistent perforators due to the
      variable anatomy. In this study, the value of color duplex imaging for reliably
      identifying the perforators of the flap was investigated. METHODS: Nineteen
      patients of various ethnicities and sex (17 men, 2 women) were studied and were
      planned to undergo reconstruction with free ALT flaps. They were evaluated using
      color duplex in the operating room before flap elevation. This imaging was
      performed in less than 20 minutes by a vascular technologist under the guidance
      of the surgeon on both thigh donor sites. RESULTS: All imaged major perforators
      were identified during flap elevation (sensitivity, 100%) and all the flaps were
      successfully elevated based on 1 or 2 identified perforators. There were no
      unexpected operative plan changes. The perforators were mapped, allowing for easy
      dissection secondary to the ability to evaluate the perforators for their size
      and location as well as potential intramuscular course. Also, the surgeons were
      able to select the side that was likely to give the highest probability of
      success. CONCLUSIONS: The color duplex scan is a useful imaging modality for
      planning and performing free ALT flap. It enables surgeons to improve efficiency
      in the operating room and overall outcomes, as well as shortens the learning
      curve when first performing these highly variable flaps. The close working
      relationship between the vascular technologist and the surgeon may be the key to
      its success.

PMID- 24667879
TI  - Management of mastectomy skin flap necrosis in autologous breast reconstruction.
AB  - INTRODUCTION: Mastectomy skin flap necrosis is a significant problem in the
      autologous breast reconstruction. The necrosis may create unsightly scarring,
      produce contour irregularities, and deform the breast mound. This may lead to a
      poor reconstruction and patient satisfaction. Most importantly, the development
      and treatment of mastectomy skin flap necrosis can delay further oncologic
      treatment.We performed a retrospective chart review of all patients undergoing
      autologous breast reconstruction in the past 5 years to examine our incidence and
      treatment of mastectomy skin flap necrosis. We then used these data to create a
      management algorithm for mastectomy skin flap necrosis. The goals of this
      algorithm were as follows: (1) to not delay further oncologic treatment, (2) to
      expedite the healing time while minimizing patient risk, and (3) to create an
      aesthetically pleasing breast reconstruction. MATERIALS AND METHODS: A
      retrospective chart review from 2008 to 2013 was performed of all autologous
      breast reconstruction at our institution. We then analyzed our data and patient
      outcomes and developed a treatment algorithm. RESULTS: We identified 204 patients
      who underwent autologous free flap breast reconstruction that was performed by
      the senior author (G.K.L.). Our incidence of mastectomy skin necrosis was 30%.
      There was no delay in adjuvant oncologic treatment for any of our patients. The
      development of mastectomy skin necrosis was significant for patients with
      diabetes (P=0.03), current tobacco use (P=0.04), and body mass index (P=0.01).
      The time for wound healing was prolonged in patients with a high body mass index
      (P=0.04). Regression analysis of wound size showed full-thickness wounds greater
      than 6 cm benefited from operative closure. CONCLUSIONS: Our incidence of
      mastectomy skin necrosis was 30%. Despite our high incidence mastectomy skin
      necrosis, we had no delays in adjuvant oncologic treatment. Retrospective data
      analysis allowed us to then develop a management algorithm for mastectomy skin
      necrosis. We feel it is advantageous to the patient and the reconstructive
      outcome to heal the breast wounds in the acute phase (within 3 weeks); and with
      regression analysis, we found full-thickness wounds greater than 6 cm benefit
      from operative intervention. Finally, patients requiring adjuvant oncologic
      treatment should be healed as quickly as possible so they may continue on with
      their oncologic care.

PMID- 24667880
TI  - Superficial Spreading Melanomas in Children: An Analysis of Outcomes Using the
      Surveillance, Epidemiology, and End Results (SEER) Database.
AB  - PURPOSE: This study aims to review the incidence and outcomes for children with
      superficial spreading melanomas (SSM) using population-based data. METHODS: The
      Surveillance, Epidemiology, and End Results database (1974-2009) was analyzed for
      all patients less than 20 years of age diagnosed with SSM. RESULTS: Overall, 724
      patients were identified. The annual age-adjusted incidence was 1.78 cases per
      1,000,000 in 2009. Most patients were adolescents (N = 620, 85.6%), girls (N =
      478, 66.0%), and Caucasian (N = 670, 92.5%). Most tumors were located on the
      trunk (N = 308, 42.5%) or lower extremities (N = 160, 22.1%). Overall and disease
      specific survivals were 95.6% and 97.6%, respectively. Lymph node positivity
      decreased disease-specific survival among patients undergoing lymph node
      dissection (86% vs. 100% for negative lymph nodes, P = 0.001). CONCLUSIONS:
      Incidence of SSM increased in the early part of the study, but has remained
      relatively stable over the past 2 decades. Girls are at higher risk of
      development of the disease. Outcomes for children with SSM are very favorable.

PMID- 24667881
TI  - Decellularization of a Fasciocutaneous Flap for Use as a Perfusable Scaffold.
AB  - BACKGROUND: The aim of the current study was to determine whether a rat
      fasciocutaneous flap could be decellularized using detergent perfusion and/or
      agitation methods while preserving the integrity of the extracellular matrix and
      circulatory networks. METHODS: Superficial inferior epigastric arterial flaps of
      50 rats were randomly divided into the following 5 groups: (1) normal; (2)
      agitation in sodium dodecyl sulfate (SDS) for 72 hours (72h-AG); (3) perfusion
      and agitation with SDS for 12 hours (12h-PE-AG); (4) perfusion and agitation with
      SDS for 24 hours (24h-PE-AG); and (5) perfusion and agitation with SDS for 72
      hours (72h-PE-AG). These flaps were evaluated by gross morphology, histology,
      integrity of the microcirculatory networks, and DNA quantification. RESULTS: The
      DNA content of the normal flap was 1.53 MUg/mg. The decellularized flaps had
      significantly reduced DNA contents: 72h-AG (0.55 MUg/mg), 12h-PE-AG (0.52
      MUg/mg), 24h-PE-AG (0.23 MUg/mg), and 72h-PE-AG (0.17 MUg/mg). The DNA contents
      in both the 24h-PE-AG and 72h-PE-AG groups were significantly less than that of
      72h-AG and 12h-PE-AG groups. These findings were confirmed by histology and gross
      morphology. The integrity of the extracellular matrix and vascular system was
      preserved as measured by collagen and elastin stains in the 4 decellularized
      groups. Despite the histological appearance of vessel integrity, none of the
      flaps maintained physiologic vascular integrity by closed-loop circulation.
      CONCLUSIONS: A combination of perfusion and agitation for 24 hours or longer
      effectively decellularized the fasciocutaneous portion of composite tissue flaps
      and removed DNA content from the flap in our rat model with well-preserved
      vascular structure. This combined technique was superior to agitation alone.
      However, closed-loop circulation could not be preserved after decellularization
      with perfusion and/or agitation methods.

PMID- 24667882
TI  - Insights from the San Francisco Match rank list data: how many interviews does it
      take to match?
AB  - BACKGROUND: For many years, the independent plastic surgery match has been
      regarded as a competitive process. Applicants expend significant time and
      resources applying to, and interviewing with, many programs to increase their
      chance for success. Public data from the San Francisco (SF) Match provide no
      predictors of success in the Match. Previous survey-based studies have provided
      some data, but suffer from recall and sampling bias. The purpose of this study
      was to provide match participants with objective primary-source data that can aid
      them in making informed decisions with regard to planning their interviews.
      METHODS: Four years of fully deidentified individual-level and program-level data
      from the SF Match (2010-2013) were analyzed. Data included number of programs
      applied to, interview offers, and length of rank lists. For applicants who
      matched, data included the applicant's rank of program and the program's rank of
      applicant. RESULTS: During the 4 match years, 434 (86.3%) of 503 applicants
      received at least 1 interview offer. Of these candidates, 355 (82%) matched.
      Match rate increased with number of interviews, reaching 96% for those with 5 or
      more interview offers; 95% of applicants matched within their top 7 choices. On
      average, applicants matched at number 2.9 on their rank lists. CONCLUSIONS:
      Number of interview invitations is a strong predictor of success in the
      independent plastic surgery match, with the "magic number" being 5. Applicants
      rarely match to programs below number 7 on their rank lists. These data can aid
      applicants wishing to maximize their potential while minimizing unnecessary
      expenditures.

PMID- 24667883
TI  - Management of head and neck melanoma: results of a national survey.
AB  - We recently reported on the safety of minimally invasive parotid region sentinel
      node biopsy and level I-sparing radical neck dissection for head and neck
      melanoma. We therefore wished to assess the state of practice in the United
      States through a survey of specialists in head and neck surgery. We hypothesized
      that there would be significant variation in the management of these facets of
      head and neck melanoma. To test this hypothesis, a 10-question online survey on
      management of head and neck melanoma was distributed to the members of the
      American Head and Neck Society. Responses were matched to Internet Protocol
      addresses to ensure that each respondent completed the survey only once. Eighty
      eight respondents completed the survey. For sentinel lymph nodes within the
      parotid gland, nearly half (47.7%) of surgeons surveyed perform a superficial
      parotidectomy, 13.6% perform a total parotidectomy, and only 38.6% perform
      parotid-sparing surgery; 71.6% of surgeons remove the submandibular nodes when
      carrying out a functional radical neck dissection. In conclusion, approaches to
      the management of head and neck melanoma vary widely, with only a minority of
      surgeons using morbidity-sparing surgical approaches. This study highlights the
      need for further randomized controlled trials in the surgical management of head
      and neck melanoma. 

PMID- 24667884
TI  - Immediate, Multistaged Approach to Infected Synthetic Mesh: Outcomes After
      Abdominal Wall Reconstruction With Porcine Acellular Dermal Matrix.
AB  - BACKGROUND: Infection of synthetic mesh after abdominal wall hernia repair is a
      complex problem. The purpose of this study was to determine whether a staged
      approach to abdominal wall reconstruction (AWR) using a porcine acellular dermal
      matrix (PADM) is beneficial in the setting of infected synthetic mesh. METHODS:
      The authors performed a retrospective review of 27 patients who underwent
      immediate, staged complex AWR using PADM from 2007 to 2012. RESULTS: After a
      component separation, primary fascial closure was achieved in 21/27 (78%)
      patients, whereas 6/22 (22%) received a bridged hernia repair with PADM. Wound
      related complications developed in 7/27 (26%) patients including wound dehiscence
      6/27 (22%), surgical site infection 5/27 (19%), and hematoma 1/27 (4%). The
      hernia recurrence rate observed by 32 months was 19%. A bridged hernia repair and
      the development of a postoperative infection were associated with hernia
      recurrence, P<0.05. CONCLUSIONS: A 2-stage approach to AWR with PADM can provide
      a safe and effective solution for patients with infected synthetic mesh.

PMID- 24667885
TI  - Tobacco Use and Body Mass Index as Predictors of Outcomes in Patients Undergoing
      Breast Reduction Mammoplasty.
AB  - BACKGROUND: Breast reduction mammoplasty accounts for more than 60,000 procedures
      annually, but the literature is still sparse on outcomes, especially beyond the
      single institution perspective. The aim of this study was to seek a broader view
      by study breast reduction outcomes in the National Surgical Quality Improvement
      Program database. METHODS: The National Surgical Quality Improvement Program data
      set was queried for the Current Procedural Terminology code 19318 from the years
      2005 to 2010. The principal outcomes measured were wound complications, surgical
      site infections, and reoperations. Univariate and multivariate analysis was
      performed to identify significant relationships. RESULTS: A total of 2779
      patients were identified. The mean age was 42.7 (14.1) years and the mean body
      mass index (BMI) was 31.6 (7.0) kg/m2. Tobacco use was associated with a higher
      rate of reoperation (P = 0.02). Body mass index was identified as an independent
      risk factor for wound complications (odds ratio, 1.85, P = 0.005). Patients with
      BMI greater than 40 kg/m were significantly more likely to develop postoperative
      wound complications (P = 0.02). CONCLUSIONS: This study represents the largest
      sample on breast reduction in the literature. Age and surgeon specialty did not
      correlate with negative results. In contrast, tobacco use and BMI were associated
      with worse breast reduction outcomes.

PMID- 24667886
TI  - Toxic megacolon after abdominoplasty: a case report.
AB  - After an accepted technique of abdominoplasty, a 66-year-old woman developed
      Clostridium difficile-associated diarrhea, leading to toxic megacolon and
      subsequent subtotal colectomy. The presumed etiology is chronic use of a proton
      pump inhibitor. This was addressed in a 2012 "white paper" warning issued by the
      Food and Drug Administration. This article presents the course of this case as
      well as a review of the pertinent literature. 

PMID- 24667888
TI  - Ligand tuning of single-site manganese-based catalytic antioxidants with dual
      superoxide dismutase and catalase activity.
AB  - A bio-inspired manganese(ii) complex with a linear pentadentate ligand framework
      containing soft sulfur donors and an alternating NSNSN binding motif displays
      excellent dual CAT/SOD-like antioxidant activity with high turnover efficiency
      and good operation stability in an aqueous environment. 

PMID- 24667887
TI  - Sleep and energy intake in early childhood.
AB  - BACKGROUND AND OBJECTIVES: Shorter sleep is associated with higher weight in
      children, but little is known about the mechanisms. The aim of this study was to
      test the hypothesis that shorter sleep was associated with higher energy intake
      in early childhood. METHODS: Participants were 1303 families from the Gemini twin
      birth cohort. Sleep duration was measured using the Brief Infant Sleep
      Questionnaire when the children were 16 months old. Total energy intake (kcal per
      day) and grams per day of fat, carbohydrate and protein were derived from 3-day
      diet diaries completed by parents when children were 21 months old. RESULTS:
      Shorter nighttime sleep was associated with higher total energy intake (P for
      linear trend=0.005). Children sleeping <10 h consumed around 50 kcal per day more
      than those sleeping 11-<12 h a night (the optimal sleep duration for children of
      this age). Differences in energy intake were maintained after adjustment for
      confounders. As a percentage of total energy intake, there were no significant
      differences in macronutrient intake by sleep duration. The association between
      sleep and weight was not significant at this age (P=0.13). CONCLUSIONS: This
      study provides the first evidence that shorter nighttime sleep duration has a
      linear association with higher energy intake early in life. That the effect is
      observed before emergence of associations between sleep and weight indicates that
      differences in energy intake may be a mechanism through which sleep influences
      weight gain.

PMID- 24667889
TI  - Halide ion-mediated growth of single crystalline Fe nanoparticles.
AB  - We report a facile halide ion (Cl(-) or Br(-)) mediated synthesis of Fe
      nanoparticles (NPs) by thermal decomposition of Fe(CO)5. The NP structure is
      controlled to be either amorphous (in the absence of halide ions) or single
      crystalline bcc (in the presence of halide ions). Through systematic
      investigation on the synthetic conditions, we have confirmed that the formation
      of bcc-Fe NPs is facilitated by the strong interactions between halide ions and
      Fe, which favor thermodynamic growth of Fe over the existing Fe NPs. Compared
      with the amorphous Fe NPs, the bcc-Fe NPs exhibit much enhanced magnetization
      values and chemical stability. This halide ion mediated growth may become a
      general strategy to control the growth of metallic NPs, especially first-row
      transition metal NPs, in a thermodynamically more stable way, producing single
      crystalline NPs with much controlled physical and chemical properties for
      magnetic and catalytic applications. 

PMID- 24667890
TI  - Fifteen-minute consultation: the child with idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IIH) is a rare condition where intracranial
      hypertension is found in the context of normal brain parenchyma and no mass
      lesion, ventriculomegaly, underlying infection, or malignancy. Our understanding
      of this condition has greatly improved in the recent years with neuroimaging
      features and normal values for lumbar puncture opening pressure now well defined.
      This article provides a review of IIH in children and revised diagnostic criteria
      based on recent evidence and published opinion. We have also presented an
      algorithmic approach to the child with possible IIH. 

PMID- 24667891
TI  - Bilayer stabilized Ln3+-doped CaMoO4 nanocrystals with high luminescence quantum
      efficiency and photocatalytic properties.
AB  - In this article, we discuss the microwave synthesis of sodium dodecyl sulphate
      (SDS) stabilized Ln(3+)-doped CaMoO4 nanocrystals (Ln(3+) = Eu(3+),
      Er(3+)/Yb(3+)). The nanocrystals are quite monodispersed with an average size
      close to 100 nm. FTIR and TGA analyses suggest strong binding of the SDS
      molecules to the CaMoO4 nanocrystals surface. The high dispersibility of the
      nanocrystals in water implies that SDS stabilizes the nanocrystals as a bilayer
      structure. The SDS coating also assists in the easy dispersion of the
      nanocrystals in toluene without any additional surface chemistry. The Eu(3+) ions
      doped in the CaMoO4 nanocrystals display very strong red luminescence with a
      quantum yield close to 40%. Under 980 nm excitation, Er(3+)/Yb(3+)-doped CaMoO4
      nanocrystals display Er(3+) emissions at 550 and 650 nm. In addition,
      interestingly, a NIR peak at around 833 nm is observed, which occurred via a
      three photon process. Furthermore, the CaMoO4 nanocrystals exhibit photocatalytic
      activity which is studied through the degradation of Rhodamine B (RhB) dye in
      neutral conditions. The RhB dye is significantly degraded by ~80% under UV
      illumination within 4 h and the rate of degradation is comparable to that
      observed for well known ZnO nanoparticles. The high luminescence quantum
      efficiency and strong photocatalytic activity of the Ln(3+)-doped CaMoO4
      nanocrystals make them a potential material for dual applications such as bio
      imaging and photocatalysis.

PMID- 24667892
TI  - Haemopneumothorax related to acupuncture.

PMID- 24667893
TI  - In-silico analysis of binding site features and substrate selectivity in plant
      flavonoid-3-O glycosyltransferases (F3GT) through molecular modeling, docking and
      dynamics simulation studies.
AB  - Flavonoids are a class of plant secondary metabolites that act as storage
      molecules, chemical messengers, as well as participate in homeostasis and defense
      processes. They possess pharmaceutical properties important for cancer treatment
      such as antioxidant and anti-tumor activities. The drug-related properties of
      flavonoids can be improved by glycosylation. The enzymes glycosyltransferases
      (GTs) glycosylate acceptor molecules in a regiospecific manner with the help of
      nucleotide sugar donor molecules. Several plant GTs have been characterized and
      their amino acid sequences determined. However, three-dimensional structures of
      only a few are reported. Here, phylogenetic analysis using amino acid sequences
      have identified a group of GTs with the same regiospecific activity. The
      structures of these closely related GTs were modeled using homologous GT
      structures. Their substrate binding sites were elaborated by docking flavonoid
      acceptor and UDP-sugar donor molecules in the modeled structures. Eight regions
      near the acceptor binding site in the N- and C- terminal domain of GTs have been
      identified that bind and specifically glycosylate the 3-OH group of acceptor
      flavonoids. Similarly, a conserved motif in the C-terminal domain is known to
      bind a sugar donor substrate. In certain GTs, the substitution of a specific
      glutamine by histidine in this domain changes the preference of sugar from
      glucose to galactose as a result of changed pattern of interactions. The
      molecular modeling, docking, and molecular dynamics simulation studies have
      revealed the chemical and topological features of the binding site and thus
      provided insights into the basis of acceptor and donor recognition by GTs. 

PMID- 24667894
TI  - Gender-specific impacts of apnea, age, and BMI on parasympathetic nerve
      dysfunction during sleep in patients with obstructive sleep apnea.
AB  - BACKGROUND: The gender-specific influences of various confounding factors,
      including apnea, age, BMI, and cigarette consumption, on the function of the
      parasympathetic nerve system (PNS) during sleep in OSA patients has never been
      investigated. METHODS: One hundred ninety-seven males and 63 females with OSA
      were subjected to full PSG examinations including assessment of R-R intervals
      (RRIs) during an overnight ECG. The PNS-derived modulatory effect on the RRIs and
      the variability of this effect were quantified during REM and NREM using
      instantaneous time-frequency analysis with complex demodulation. The spectral
      domain with the maximum instantaneous amplitude in the high-frequency band
      between 0.15 and 0.4 Hz was defined as the main HF peak and used as a surrogate
      marker of PNS discharge. Based on density-spectrum-array maps of the main HF
      peaks (HF-DSA map), shifts in the central frequency of the main HF peak over time
      were continuously observed. When the main HF peaks on the HF-DSA maps maintained
      the same central frequency for more than 20 sec or 5 min, the PNS functions were
      considered to be "stable" or "very stable", respectively. RESULTS: Apneas
      enhanced PNS-derived cardiac-modulation during REM in males, but more
      importantly, they made PNS-function unstable during both REM and NREM in males
      and during NREM in females. Aging blunted the PNS-derived cardiac-modulation
      during both REM and NREM regardless of gender, but aging had no impact on the
      stability of PNS-function. BMI blunted PNS-eliciting cardiac-modulation during
      REM in males and during NREM in both males and females. BMI made the PNS unstable
      during REM in females. Neither height nor cigarette consumption influenced any
      PNS-related parameter. CONCLUSIONS: The PNS-derived cardiac-modulation was
      generally inhibited by aging and obesity, in which the effect of obesity was
      gender-specific. The PNS instability at nighttime was mainly induced by apneas
      but by obesity particularly during REM in females.

PMID- 24667896
TI  - The window of desiccation tolerance shown by early-stage germinating seedlings
      remains open in the resurrection plant, Xerophyta viscosa.
AB  - Resurrection plants are renowned for their vegetative desiccation tolerance (DT).
      While DT in vegetative tissues is rare in angiosperms, it is ubiquitous in mature
      orthodox seeds. During germination, seedlings gradually lose DT until they pass a
      point of no return, after which they can no longer survive dehydration. Here we
      investigate whether seedlings of the resurrection plant Xerophyta viscosa ever
      lose the capacity to establish DT. Seedlings from different stages of germination
      were dehydrated for 48 hours and assessed for their ability to recover upon
      rehydration. While a transient decline in the ability of X. viscosa seedlings to
      survive dehydration was observed, at no point during germination was the ability
      to re-establish DT completely lost in all seedlings. Pre-treatment of seedlings
      with PEG or sucrose reduced this transient decline, and improved the survival
      rate at all stages of germination. Additionally, we observed that the trait of
      poikilochlorophylly (or loss of chlorophyll) observed in adult X. viscosa leaves
      can be induced throughout seedling development. These results suggest that the
      window of DT seen in germinating orthodox seeds remains open in X. viscosa
      seedlings and that vegetative DT in Xerophyta species may have evolved from the
      ability to retain this program through to adulthood. 

PMID- 24667897
TI  - Force spectroscopy of polymer desorption: theory and molecular dynamics
      simulations.
AB  - Forced detachment of a single polymer chain, strongly adsorbed on a solid
      substrate, is investigated by two complementary methods: a coarse-grained
      analytical dynamical model, based on the Onsager stochastic equation, and
      Molecular Dynamics (MD) simulations with a Langevin thermostat. The suggested
      approach makes it possible to go beyond the limitations of the conventional Bell
      Evans model. We observe a series of characteristic force spikes when the pulling
      force is measured against the cantilever displacement during detachment at
      constant velocity vc (displacement control mode) and find that the average
      magnitude of this force increases as vc increases. The probability distributions
      of the pulling force and the end-monomer distance from the surface at the moment
      of the final detachment are investigated for different adsorption energies
      epsilon and pulling velocities vc. Our extensive MD simulations validate and
      support the main theoretical findings. Moreover, the simulations reveal a novel
      behavior: for a strong-friction and massive cantilever the force spike pattern is
      smeared out at large vc. As a challenging task for experimental bio-polymer
      sequencing in future we suggest the fabrication of a stiff, super-light,
      nanometer-sized AFM probe. 

PMID- 24667899
TI  - The autoantibody repertoire in periodontitis: a role in the induction of
      autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies
      against uncitrullinated peptides seem to occur prior to the antibodies to the
      corresponding citrullinated peptides.

PMID- 24667900
TI  - Effect of home-based hand exercises in women with hand osteoarthritis: a
      randomised controlled trial.
AB  - BACKGROUND: Hand exercises are recommended for patients with hand osteoarthritis
      (HOA), though evidence for their effect is conflicting. OBJECTIVE: To evaluate,
      in a randomised controlled trial, the effect of HOA information plus home-based
      hand exercises (exercise group) compared with information only (control group) in
      women with HOA. METHODS: Interventions were delivered by two occupational
      therapists. Exercise group participants received eight follow-up calls over the 3
      month study and recorded adherence, pain after exercises and adverse events in a
      diary. Primary outcome was activity performance measured after 3 months by the
      Patient-Specific Functional Scale (PSFS), with a range of 0-10. Secondary
      outcomes were measurements of hand function, disease activity, symptoms and
      number of responders to treatment according to the OMERACT-OARSI criteria.
      RESULTS: Of 80 women randomised (40 : 40) (mean age (SD) 60.8 years (7.0)),
      follow-up was 89% (n=71). An intention-to-treat analysis was performed. The
      adjusted mean difference for the exercise versus control group was 1.4 points
      (95% CI 0.6 to 2.2, effect size 1.0) for the PSFS score. Thirteen patients in the
      exercise group versus three participants in the control group reached a positive
      minimal clinical important difference of 2.2 points in the PSFS total score,
      while none versus two, respectively, had a negative change (p=0.007). For
      secondary outcomes, significant mean differences were found in grip strength and
      thumb web space, in fatigue, joint pain and the Functional Index for HOA activity
      performance scores. Sixteen exercise-group participants fulfilled the OMERACT
      OARSI response criteria versus two control-group participants (p<0.001).
      CONCLUSIONS: Hand exercises were well tolerated and significantly improved
      activity performance, grip strength, pain and fatigue in women with HOA. TRIAL
      REGISTRATION NUMBER: ISRTCN79019063.

PMID- 24667898
TI  - Structural reorganization of pyramidal neurons in the medial prefrontal cortex of
      alcohol dependent rats is associated with altered glial plasticity.
AB  - In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol
      dependence, alters the activity of pyramidal neurons and decreases the number of
      glial progenitors in the medial prefrontal cortex (mPFC). Adult male Wistar rats
      were exposed to CIE and were injected with mitotic markers to label and phenotype
      proliferating cells to test the hypothesis that CIE produces concurrent
      alterations in the structure of pyramidal neurons and the cell cycle kinetics and
      developmental stages of glial progenitors in the mPFC. Medial prefrontal cortical
      tissue was processed for Golgi-Cox staining, immunohistochemistry and Western
      blotting analysis. CIE increased dendritic arborization and spine densities
      within basal and apical dendrites of pyramidal neurons via aberrant
      reorganization of actin cytoskeleton-associated molecules. CIE concomitantly
      increased the expression of total NR2B subunits without affecting phosphorylation
      of NR2B at Tyr-1472 or levels of PSD-95. CIE reduced the length of S-phase of the
      cell cycle of glial progenitors and reduced proliferation and differentiation of
      progenitors into bHLH transcription factor Olig2-expressing premyelinating
      oligodendrocyte progenitor cells (OPCs). CIE also produced a corresponding
      hyperphosphorylation of Olig2, and reduced expression of myelin basic protein.
      Our findings demonstrate that CIE-induced alterations in OPCs and myelin-related
      proteins are associated with profound alterations in the structure of pyramidal
      neurons. In sum, our results not only provide evidence that alcohol dependence
      leads to pathological changes in the mPFC, which may in part define a cellular
      basis for cognitive impairments associated with alcoholism, but also show
      dependence-associated morphological changes in the PFC at the single neuron
      level. 

PMID- 24667901
TI  - On the possible biological relevance of HSNO isomers: a computational
      investigation.
AB  - Thionitrous acid (HSNO), the smallest S-nitrosothiol, has been identified as a
      potential biologically active molecule that connects the biochemistries of two
      important gasotransmitters, nitric oxide (NO) and hydrogen sulfide (H2S). Here,
      we computationally explore possible isomerization reactions of HSNO that may
      occur under physiological conditions using high-level coupled-cluster as well as
      density functional theory and composite CBS-QB3 methodology calculations. Gas
      phase calculations show that the formation of the tautomeric form HONS and the Y
      isomer SN(H)O is thermodynamically feasible, as they are energetically close,
      within ~6 kcal mol(-1), to HSNO, while the recently proposed three-membered ring
      isomer is not thermodynamically or kinetically accessible. The gas-phase
      intramolecular proton-transfer reactions required for HSNO isomerization into
      HONS and SN(H)O are predicted to have prohibitively high reaction barriers, 30-50
      kcal mol(-1). However, the polar aqueous environment and water-assisted proton
      shuttle should decrease these barriers to ~9 kcal mol(-1), which makes these two
      isomers kinetically accessible under physiological conditions. Our calculations
      also support the possibility of an aqueous reaction between the Y-isomer SN(H)O
      and H2S leading to biologically active nitroxyl HNO. These results suggest that
      the formation of HSNO in biological milieu can lead to various derivative species
      with their own, possibly biologically relevant, activity. 

PMID- 24667902
TI  - An electrochemical method for the synthesis of few layer graphene sheets for high
      temperature applications.
AB  - We demonstrate an electrochemical technique for the large scale synthesis of high
      quality few layer graphene sheets (FLGS) directly from graphite using oxalic acid
      (a weak acid) as the electrolyte. One of the interesting observations is that the
      FLGS are stable at least up to 800  degrees C and hence have potential
      application in solid oxide fuel cells as a gas diffusion layer. 

PMID- 24667904
TI  - Diagnosis of posterior cortical atrophy delayed by coexisting Fuchs' Endothelial
      Corneal Dystrophy.
AB  - Posterior cortical atrophy (PCA), also known as the visual variant of Alzheimer's
      Disease, is a rare neurodegenerative disorder that affects the visuospatial
      systems in its initial stages. Due to the rarity of this condition and the
      presence of relatively preserved memory during its early stages compared to other
      dementias, its accurate diagnosis can be delayed. When accompanied by a comorbid
      visual disorder, the diagnostic process becomes even more challenging. This study
      describes the disease course of a patient whose diagnosis of Fuchs' Endothelial
      Corneal Dystrophy served to delay an additional diagnosis of PCA, illustrating
      the necessity of careful scrutiny of symptom presentation and especially its
      course.

PMID- 24667905
TI  - Feasibility and efficacy of intensive cognitive training in early-stage
      Alzheimer's disease.
AB  - Cognitive training may be beneficial for individuals with Alzheimer's disease
      (AD); however, the effects are modest with little evidence of carryover. Prior
      studies included limited hours and low intensity of training. The purpose of this
      study was to test the feasibility and efficacy of many hours of intensive
      cognitive training with adults in the early stages of AD. Twenty-one adults with
      very mild or mild AD participated in cognitive training for 10 days over 2 weeks
      with 4 to 5 hours of training each day. Participants significantly improved in
      practiced computer-based tasks including those involving working memory,
      sustained attention, and switching attention. Outcome measures that improved
      included the Mini-Mental State Examination, letter fluency, and 3 of 5 Trail
      Making Tests. Gains in outcome measures were maintained at 2- and 4-month follow
      up. Adults in early-stage AD can participate in intensive cognitive training and
      make modest gains in both practiced and unpracticed cognitive tasks.

PMID- 24667908
TI  - An analysis of 24-h ambulatory blood pressure monitoring data using orthonormal
      polynomials in the linear mixed model.
AB  - BACKGROUND: The use of 24-h ambulatory blood pressure monitoring (ABPM) in
      clinical practice and observational epidemiological studies has grown
      considerably in the past 25 years. ABPM is a very effective technique for
      assessing biological, environmental, and drug effects on blood pressure.
      OBJECTIVES: In order to enhance the effectiveness of ABPM for clinical and
      observational research studies using analytical and graphical results, developing
      alternative data analysis approaches using modern statistical techniques are
      important. METHODS: The linear mixed model for the analysis of longitudinal data
      is particularly well suited for the estimation of, inference about, and
      interpretation of both population (mean) and subject-specific trajectories for
      ABPM data. We propose using a linear mixed model with orthonormal polynomials
      across time in both the fixed and random effects to analyze ABPM data. RESULTS:
      We demonstrate the proposed analysis technique using data from the Dietary
      Approaches to Stop Hypertension (DASH) study, a multicenter, randomized, parallel
      arm feeding study that tested the effects of dietary patterns on blood pressure.
      CONCLUSION: The linear mixed model is relatively easy to implement (given the
      complexity of the technique) using available software, allows for straightforward
      testing of multiple hypotheses, and the results can be presented to research
      clinicians using both graphical and tabular displays. Using orthonormal
      polynomials provides the ability to model the nonlinear trajectories of each
      subject with the same complexity as the mean model (fixed effects).

PMID- 24667909
TI  - Vibrio cholerae persisted in microcosm for 700 days inhibits motility but
      promotes biofilm formation in nutrient-poor lake water microcosms.
AB  - Toxigenic Vibrio cholerae, ubiquitous in aquatic environments, is responsible for
      cholera; humans can become infected after consuming food and/or water
      contaminated with the bacterium. The underlying basis of persistence of V.
      cholerae in the aquatic environment remains poorly understood despite decades of
      research. We recently described a "persister" phenotype of V. cholerae that
      survived in nutrient-poor "filter sterilized" lake water (FSLW) in excess of 700
      days. Previous reports suggest that microorganisms can assume a growth advantage
      in stationary phase (GASP) phenotype in response to long-term survival during
      stationary phase of growth. Here we report a V. cholerae GASP phenotype (GASP
      700D) that appeared to result from 700 day-old persister cells stored in glycerol
      broth at -80 degrees C. The GASP-700D, compared to its wild-type N16961, was
      defective in motility, produced increased biofilm that was independent of vps
      (p<0.005) and resistant to oxidative stress when grown specifically in FSLW
      (p<0.005). We propose that V. cholerae GASP-700D represents cell populations that
      may better fit and adapt to stressful survival conditions while serving as a
      critical link in the cycle of cholera transmission. 

PMID- 24667910
TI  - Role of red blood cell lysis and iron in hydrocephalus after intraventricular
      hemorrhage.
AB  - Thrombin and iron are two major players in intracerebral hemorrhage-induced brain
      injury and our recent study found that thrombin contributes to hydrocephalus
      development in a rat model of intraventricular hemorrhage (IVH). This study
      investigated the role of red blood cell (RBC) lysis and iron in hydrocephalus
      after IVH. There were three parts to this study. First, male Sprague-Dawley rats
      received an injection of saline, packed, or lysed RBCs into the right lateral
      ventricle. Second, rats had an intraventricular injection of iron or saline.
      Third, the rats received intraventricular injection of lysed RBCs mixed with
      deferoxamine (0.5 mg in 5 MUL saline) or saline. All rats underwent magnetic
      resonance imaging at 24 hours and were then euthanized for brain edema
      measurement, western blot analysis, or brain histology. We found that
      intraventricular injection of lysed RBCs, but not packed RBCs, resulted in
      ventricular enlargement and marked increases in brain heme oxygenase-1 and
      ferritin at 24 hours. Intraventricular injection of iron also resulted in
      ventricular enlargement and ventricular wall damage 24 hours later. Coinjection
      of deferoxamine reduced lysed RBC-induced ventricular enlargement (P<0.01). These
      results suggest that iron, a degradation product of hemoglobin, has an important
      role in hydrocephalus development after IVH. 

PMID- 24667911
TI  - Kinetic modeling without accounting for the vascular component impairs the
      quantification of [(11)C]PBR28 brain PET data.
AB  - The positron emission tomography radioligand [(11)C]PBR28 targets translocator
      protein (18 kDa) (TSPO) and is a potential marker of neuroinflammation.
      [(11)C]PBR28 binding is commonly quantified using a two-tissue compartment model
      and an arterial input function. Previous studies with [(11)C]-(R)-PK11195
      demonstrated a slow irreversible binding component to the TSPO proteins localized
      in the endothelium of brain vessels, such as venous sinuses and arteries.
      However, the impact of this component on the quantification of [(11)C]PBR28 data
      has never been investigated. In this work we propose a novel kinetic model for
      [(11)C]PBR28. This model hypothesizes the existence of an additional irreversible
      component from the blood to the endothelium. The model was tested on a data set
      of 19 healthy subjects. A simulation was also performed to quantify the error
      generated by the standard two-tissue compartmental model when the presence of the
      irreversible component is not taken into account. Our results show that when the
      vascular component is included in the model the estimates that include the
      vascular component (2TCM-1K) are more than three-fold smaller, have a higher time
      stability and are better correlated to brain mRNA TSPO expression than those that
      do not include the model (2TCM). 

PMID- 24667912
TI  - Brown adipose tissue function is accompanied by cerebral activation in lean but
      not in obese humans.
AB  - Brown adipose tissue (BAT) is able to generate heat and dissipate energy in
      response to cold exposure in mammals. It has recently been acknowledged that
      adult humans also have functional BAT, whose metabolic activity is reduced in
      obesity. In healthy humans, the cerebral mechanisms that putatively control BAT
      function are unclear. By using positron emission tomography (PET), we showed that
      cold-induced BAT activation is associated with glucose metabolism in the
      cerebellum, thalamus, and cingulate, temporoparietal, lateral frontal, and
      occipital cortices in lean participants, whereas no such associations were found
      under warm control conditions. The cold-induced increase in cerebral glucose
      metabolism was more robust in lean than obese participants. Cerebral glucose
      metabolism was not associated with skeletal muscle or white adipose tissue
      glucose uptake under warm or cold conditions. In conclusion, BAT metabolism was
      accompanied by the activation of specific cerebral regions, and this shows an
      uncharacterized role that the brain plays in the regulation of BAT function. In
      obese participants, the cold-induced response in cerebral activity was attenuated
      that provides a clue for obesity-induced impairment in BAT metabolism. 

PMID- 24667914
TI  - The proteome of mouse cerebral arteries.
AB  - The cerebral vasculature ensures proper cerebral function by transporting oxygen,
      nutrients, and other substances to the brain. Distribution of oxygenated blood
      throughout the neuroaxis takes place at the level of the circle of Willis (CW).
      While morphologic and functional alterations in CW arteries and its main branches
      have been reported in cerebrovascular and neurodegenerative diseases,
      accompanying changes in protein expression profiles remain largely
      uncharacterized. In this study, we performed proteomics to compile a novel list
      of proteins present in mouse CW arteries and its ramifications. Circle of Willis
      arteries were surgically removed from 6-month-old wild-type mice, proteins
      extracted and analyzed by two proteomics approaches, gel-free nanoLC-mass
      spectrometry (MS)/MS and gel-based GelLC-MS/MS, using nanoAcquity UPLC coupled
      with ESI-LTQ Orbitrap XL. The two approaches helped maximize arterial proteome
      coverage. Six biologic and two technical replicates were performed. In all, 2,188
      proteins with at least 2 unique high-scoring peptides were identified (6,630
      proteins total). Proteins were classified according to vasoactivity, blood-brain
      barrier specificity, tight junction and adhesion molecules, membrane
      transporters/channels, and extracellular matrix/basal lamina proteins.
      Furthermore, we compared the identified CW arterial proteome with the published
      brain microvascular proteome. Our database provides a vital resource for the
      study of CW cerebral arterial protein expression profiles in health and disease. 

PMID- 24667915
TI  - Protein kinase C epsilon regulates mitochondrial pools of Nampt and NAD following
      resveratrol and ischemic preconditioning in the rat cortex.
AB  - Preserving mitochondrial pools of nicotinamide adenine dinucleotide (NAD) or
      nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in NAD
      production, maintains mitochondrial function and confers neuroprotection after
      ischemic stress. However, the mechanisms involved in regulating mitochondrial
      localized Nampt or NAD have not been defined. In this study, we investigated the
      roles of protein kinase C epsilon (PKCE) and AMP-activated protein kinase (AMPK)
      in regulating mitochondrial pools of Nampt and NAD after resveratrol or ischemic
      preconditioning (IPC) in the cortex and in primary neuronal-glial cortical
      cultures. Using the specific PKCE agonist psiERACK, we found that PKCE induced
      robust activation of AMPK in vitro and in vivo and that AMPK was required for
      PKCE-mediated ischemic neuroprotection. In purified mitochondrial fractions, PKCE
      enhanced Nampt levels in an AMPK-dependent manner and was required for increased
      mitochondrial Nampt after IPC or resveratrol treatment. Analysis of intrinsic NAD
      autofluorescence using two-photon microscopy revealed that PKCE modulated NAD in
      the mitochondrial fraction. Further assessments of mitochondrial NAD
      concentrations showed that PKCE has a key role in regulating the mitochondrial
      NAD(+)/nicotinamide adenine dinucleotide reduced (NADH) ratio after IPC and
      resveratrol treatment in an AMPK- and Nampt-dependent manner. These findings
      indicate that PKCE is critical to increase or maintain mitochondrial Nampt and
      NAD after pathways of ischemic neuroprotection in the brain. 

PMID- 24667913
TI  - Mechanisms of perinatal arterial ischemic stroke.
AB  - The incidence of perinatal stroke is high, similar to that in the elderly, and
      produces a significant morbidity and severe long-term neurologic and cognitive
      deficits, including cerebral palsy, epilepsy, neuropsychological impairments, and
      behavioral disorders. Emerging clinical data and data from experimental models of
      cerebral ischemia in neonatal rodents have shown that the pathophysiology of
      perinatal brain damage is multifactorial. These studies have revealed that, far
      from just being a smaller version of the adult brain, the neonatal brain is
      unique with a very particular and age-dependent responsiveness to hypoxia
      ischemia and focal arterial stroke. In this review, we discuss fundamental
      clinical aspects of perinatal stroke as well as some of the most recent and
      relevant findings regarding the susceptibility of specific brain cell populations
      to injury, the dynamics and the mechanisms of neuronal cell death in injured
      neonates, the responses of neonatal blood-brain barrier to stroke in relation to
      systemic and local inflammation, and the long-term effects of stroke on
      angiogenesis and neurogenesis. Finally, we address translational strategies
      currently being considered for neonatal stroke as well as treatments that might
      effectively enhance repair later after injury. 

PMID- 24667916
TI  - Ultrafast Doppler reveals the mapping of cerebral vascular resistivity in
      neonates.
AB  - In vivo mapping of the full vasculature dynamics based on Ultrafast Doppler is
      showed noninvasively in the challenging case of the neonatal brain. Contrary to
      conventional pulsed-wave (PW) Doppler Ultrasound limited for >40 years to the
      estimation of vascular indices at a single location, the ultrafast frame rate
      (5,000 Hz) obtained using plane-wave transmissions leads to simultaneous
      estimation of full Doppler spectra in all pixels of wide field-of-view images
      within a single cardiac cycle and high sensitivity Doppler imaging. Consequently,
      2D quantitative maps of the cerebro-vascular resistivity index (RI) are processed
      and found in agreement with local measurements obtained on large arteries of
      healthy neonates using conventional PW Doppler. Changes in 2D resistivity maps
      are monitored during recovery after therapeutic whole-body cooling of full-term
      neonates treated for hypoxic ischemic encephalopathy. Arterial and venous vessels
      are unambiguously differentiated on the basis of their distinct hemodynamics. The
      high spatial (250 * 250 MUm(2)) and temporal resolution (<1 ms) of Ultrafast
      Doppler imaging combined with deep tissue penetration enable precise quantitative
      mapping of deep brain vascular dynamics and RI, which is far beyond the
      capabilities of any other imaging modality. 

PMID- 24667917
TI  - Short-term high-fat-and-fructose feeding produces insulin signaling alterations
      accompanied by neurite and synaptic reduction and astroglial activation in the
      rat hippocampus.
AB  - Chronic consumption of high-fat-and-fructose diets (HFFD) is associated with the
      development of insulin resistance (InsRes) and obesity. Systemic insulin
      resistance resulting from long-term HFFD feeding has detrimental consequences on
      cognitive performance, neurogenesis, and long-term potentiation establishment,
      accompanied by neuronal alterations in the hippocampus. However, diet-induced
      hippocampal InsRes has not been reported. Therefore, we investigated whether
      short-term HFFD feeding produced hippocampal insulin signaling alterations
      associated with neuronal changes in the hippocampus. Rats were fed with a control
      diet or an HFFD consisting of 10% lard supplemented chow and 20% high-fructose
      syrup in the drinking water. Our results show that 7 days of HFFD feeding induce
      obesity and InsRes, associated with the following alterations in the hippocampus:
      (1) a decreased insulin signaling; (2) a decreased hippocampal weight; (3) a
      reduction in dendritic arborization in CA1 and microtubule-associated protein 2
      (MAP-2) levels; (4) a decreased dendritic spine number in CA1 and synaptophysin
      content, along with an increase in tau phosphorylation; and finally, (5) an
      increase in reactive astrocyte associated with microglial changes. To our
      knowledge, this is the first report addressing hippocampal insulin signaling, as
      well as morphologic, structural, and functional modifications due to short-term
      HFFD feeding in the rat. 

PMID- 24667918
TI  - Differential effects of Tat proteins derived from HIV-1 subtypes B and
      recombinant CRF02_AG on human brain microvascular endothelial cells: implications
      for blood-brain barrier dysfunction.
AB  - HIV-1 genetic differences influence viral replication and progression to AIDS.
      HIV-1 circulating recombinant form (CRF)02_AG is the predominant viral subtype
      infecting humans in West and Central Africa, but its effects on HIV
      neuropathogenesis are not known. In the present study, we investigated the
      effects of Tat proteins from HIV-1 subtype B (Tat.B) and HIV-1 CRF02_AG (Tat.AG)
      on primary human brain microvascular endothelial cells (HBMEC), the major
      component of the blood-brain barrier (BBB). Using Affymetrix GeneChip Human Gene
      1.0.ST arrays, we showed that Tat.AG had minimal effects while Tat.B induced
      transcriptional upregulation of 90 genes in HBMEC, including proinflammatory
      chemokines, complement components C3, C7, and complement factor B, matrix
      metalloproteinases (MMP)-3, MMP-10, and MMP-12. These results were confirmed by
      real-time PCR. Compared with Tat.AG, Tat.B significantly increased MMP-3, MMP-10,
      and MMP-12 activities in HBMEC, and the MMPs tissue inhibitor of
      metalloproteinase-2 blocked Tat-induced increase in MMPs activity. Western blot
      analyses also showed that Tat increased the expression of C3 and its cleaved
      fragment C3b in HBMEC. These data suggest that genetic differences between HIV-1
      subtypes B and CRF02_AG influence the effects of Tat proteins from these two
      clades on HBMEC, including molecular and cellular functions, and canonical
      pathways, which would affect BBB dysfunction and viral neuropathogenesis. 

PMID- 24667920
TI  - Clinical meaning of the GRADE rules.

PMID- 24667921
TI  - Serum myeloid-related protein 8/14 complex is associated with microalbuminuria in
      patients with type 2 diabetes.
AB  - OBJECTIVES: Microalbuminuria (MA) is associated independently with cardiovascular
      risk and progression of renal disease in patients with diabetes and the normal
      population. MA is an accepted factor for microvascular defects, in particular in
      patients with diabetes, and is associated with inflammation. Activated
      transmigrating macrophages are key cells in these inflammatory processes. Based
      on the theory that myeloid-related protein 8/14 complex (MRP8/14) is secreted by
      transmigrating macrophages, we hypothesized that MA was accompanied by elevated
      MRP8/14 and investigated whether MA predicts MRP8/14 in patients with type 2
      diabetes. METHODS: A total of 86 men with type 2 diabetes were grouped according
      to urinary albumin excretion in normoalbuminuria and MA. Serum MRP8/14 levels
      were measured by enzyme-linked immunosorbent assay. Established cardiovascular
      risk factors were quantified in both groups and compared with urinary albumin
      excretion. RESULTS: Albuminuria (mg/day) was positively associated with MRP8/14
      (r = 0.34) and systemic blood pressure (r = 0.33). Patients with type 2 diabetes
      and MA demonstrated significantly higher MRP8/14 levels than patients with
      normoalbuminuria [median (interquartile range), 1.24 (0.97-2.28) ug/ml versus
      0.97 (0.67-1.35) ug/ml, p < 0.05]. Serum creatinine levels, systolic blood
      pressure (SBP), very low density lipoprotein levels and the incidence of
      hypertension and coronary artery disease were significantly higher in the group
      with MA. Both groups did not differ significantly in other cardiovascular risk
      factors. MA was an independent predictor of serum MRP8/14 levels (beta = 0.454)
      as well as SBP (beta = 0.625) and haemoglobin A1c (beta = 0.322). CONCLUSION: Our
      data demonstrate that albumin excretion is associated with the process of
      macrophage activation determined by MRP8/14 levels. These data not only suggest
      tissue inflammation as a factor for elevated cardiovascular risk in patients with
      type 2 diabetes, they further point to a role of macrophage activation in this
      process.

PMID- 24667922
TI  - Controlled thioamide vs. amide formation in the thioacid-azide reaction under
      acidic aqueous conditions.
AB  - The thioacid-azide reaction and its chemoselectivity were probed with alkyl
      azides for a potential application to form amide bonds in aqueous solvents. Our
      results reveal that under acidic conditions thioamides were formed as major
      reaction products suggesting a competing mechanism, whereas reactions forming
      amides predominated at slightly higher pH values. 

PMID- 24667919
TI  - Effects of interventions on survival in acute respiratory distress syndrome: an
      umbrella review of 159 published randomized trials and 29 meta-analyses.
AB  - PURPOSE: Multiple interventions have been tested in acute respiratory distress
      syndrome (ARDS). We examined the entire agenda of published randomized controlled
      trials (RCTs) in ARDS that reported on mortality and of respective meta-analyses.
      METHODS: We searched PubMed, the Cochrane Library, and Web of Knowledge until
      July 2013. We included RCTs in ARDS published in English. We excluded trials of
      newborns and children; and those on short-term interventions, ARDS prevention, or
      post-traumatic lung injury. We also reviewed all meta-analyses of RCTs in this
      field that addressed mortality. Treatment modalities were grouped in five
      categories: mechanical ventilation strategies and respiratory care, enteral or
      parenteral therapies, inhaled/intratracheal medications, nutritional support, and
      hemodynamic monitoring. RESULTS: We identified 159 published RCTs of which 93 had
      overall mortality reported (n = 20,671 patients)--44 trials (14,426 patients)
      reported mortality as a primary outcome. A statistically significant survival
      benefit was observed in eight trials (seven interventions) and two trials
      reported an adverse effect on survival. Among RCTs with more than 50 deaths in at
      least one treatment arm (n = 21), two showed a statistically significant
      mortality benefit of the intervention (lower tidal volumes and prone
      positioning), one showed a statistically significant mortality benefit only in
      adjusted analyses (cisatracurium), and one (high-frequency oscillatory
      ventilation) showed a significant detrimental effect. Across 29 meta-analyses,
      the most consistent evidence was seen for low tidal volumes and prone positioning
      in severe ARDS. CONCLUSIONS: There is limited supportive evidence that specific
      interventions can decrease mortality in ARDS. While low tidal volumes and prone
      positioning in severe ARDS seem effective, most sporadic findings of
      interventions suggesting reduced mortality are not corroborated consistently in
      large-scale evidence including meta-analyses.

PMID- 24667923
TI  - Improved diagnosis of idiopathic giant cell myocarditis and cardiac sarcoidosis
      by myocardial gene expression profiling.
AB  - AIMS: Improvement of clinical diagnostics of idiopathic giant cell myocarditis
      (IGCM) and cardiac sarcoidosis (CS), two frequently fatal human myocardial
      diseases. Currently, IGCM and CS are diagnosed based on differential patterns of
      inflammatory cell infiltration and non-caseating granulomas in histological
      sections of endomyocardial biopsies (EMBs), after heart explantation or
      postmortem. We report on a method for improved differential diagnosis by
      myocardial gene expression profiling in EMBs. METHODS AND RESULTS: We examined
      gene expression profiles in EMBs from 10 patients with histopathologically proven
      IGCM, 10 with CS, 18 with active myocarditis (MCA), and 80 inflammation-free
      control subjects by quantitative RT-QPCR. We identified distinct differential
      profiles that allowed a clear discrimination of tissues harbouring giant cells
      (IGCS, CS) from those with MCA or inflammation-free controls. The expression
      levels of genes coding for cytokines or chemokines (CCL20, IFNB1, IL6, IL17D; P <
      0.05), cellular receptors (ADIPOR2, CCR5, CCR6, TLR4, TLR8; P < 0.05), and
      proteins involved in the mitochondrial energy metabolism (CPT1, CYB, DHODH; P <
      0.05) were deregulated in 2- to 300-fold, respectively. Bioinformatic analyses
      and correlation of the gene expression data with immunohistochemical findings
      provided novel information regarding the differential cellular and molecular
      pathomechanisms in IGCM, CS, and MCA. CONCLUSION: Myocardial gene expression
      profiling is a reliable method to predict the presence of multinuclear giant
      cells in the myocardium, even without a direct histological proof, in single
      small EMB sections, and thus to reduce the risk of sampling errors. This
      profiling also facilitates the discrimination between IGCM and CS, as two
      different clinical entities that require immediate and tailored differential
      therapy.

PMID- 24667925
TI  - Brown and polar bear Y chromosomes reveal extensive male-biased gene flow within
      brother lineages.
AB  - Brown and polar bears have become prominent examples in phylogeography, but
      previous phylogeographic studies relied largely on maternally inherited
      mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y
      chromosome, a natural counterpart to mtDNA, has remained underexplored. Although
      this paternally inherited chromosome is indispensable for comprehensive analyses
      of phylogeographic patterns, technical difficulties and low variability have
      hampered its application in most mammals. We developed 13 novel Y-chromosomal
      sequence and microsatellite markers from the polar bear genome and screened these
      in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390
      kb-long Y-chromosomal scaffold using sequencing data from published male ursine
      genomes. Y chromosome evidence support the emerging understanding that brown and
      polar bears started to diverge no later than the Middle Pleistocene. Contrary to
      mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic
      sister (or rather brother) lineages, without signals of introgression, 2) male
      biased gene flow across continents and on phylogeographic time scales, and 3)
      male dispersal that links the Alaskan ABC islands population to mainland brown
      bears. Due to female philopatry, mtDNA provides a highly structured estimate of
      population differentiation, while male-biased gene flow is a homogenizing force
      for nuclear genetic variation. Our findings highlight the importance of analyzing
      both maternally and paternally inherited loci for a comprehensive view of
      phylogeographic history, and that mtDNA-based phylogeographic studies of many
      mammals should be reevaluated. Recent advances in sequencing technology render
      the analysis of Y-chromosomal variation feasible, even in nonmodel organisms. 

PMID- 24667926
TI  - Crab nebula of life.

PMID- 24667927
TI  - Testis size matters for genome evolution.

PMID- 24667924
TI  - JAM-related proteins in mucosal homeostasis and inflammation.
AB  - Mucosal surfaces are lined by epithelial cells that form a physical barrier
      protecting the body against external noxious substances and pathogens. At a
      molecular level, the mucosal barrier is regulated by tight junctions (TJs) that
      seal the paracellular space between adjacent epithelial cells. Transmembrane
      proteins within TJs include junctional adhesion molecules (JAMs) that belong to
      the cortical thymocyte marker for Xenopus family of proteins. JAM family
      encompasses three classical members (JAM-A, JAM-B, and JAM-C) and related
      molecules including JAM4, JAM-like protein, Coxsackie and adenovirus receptor
      (CAR), CAR-like membrane protein and endothelial cell-selective adhesion
      molecule. JAMs have multiple functions that include regulation of endothelial and
      epithelial paracellular permeability, leukocyte recruitment during inflammation,
      angiogenesis, cell migration, and proliferation. In this review, we summarize the
      current knowledge regarding the roles of the JAM family members in the regulation
      of mucosal homeostasis and leukocyte trafficking with a particular emphasis on
      barrier function and its perturbation during pathological inflammation. 

PMID- 24667928
TI  - Zits, grapes, and Frank Zappa.

PMID- 24667930
TI  - Self-assembly and optical properties of a porphyrin-based amphiphile.
AB  - A porphyrin-based amphiphile that exhibits various self-assembled nanostructures
      in different solvents has been successfully prepared. The effect of aggregated
      structure on optical properties of this amphiphile has been well investigated.
      Furthermore, this porphyrin-based amphiphile and its assemblies show
      dynamic/reversible variations in morphology and optical properties in response to
      light. 

PMID- 24667929
TI  - Comparison of seasonal soil microbial process in snow-covered temperate
      ecosystems of northern China.
AB  - More than half of the earth's terrestrial surface currently experiences seasonal
      snow cover and soil frost. Winter compositional and functional investigations in
      soil microbial community are frequently conducted in alpine tundra and boreal
      forest ecosystems. However, little information on winter microbial
      biogeochemistry is known from seasonally snow-covered temperate ecosystems. As
      decomposer microbes may differ in their ability/strategy to efficiently use soil
      organic carbon (SOC) within different phases of the year, understanding seasonal
      microbial process will increase our knowledge of biogeochemical cycling from the
      aspect of decomposition rates and corresponding nutrient dynamics. In this study,
      we measured soil microbial biomass, community composition and potential SOC
      mineralization rates in winter and summer, from six temperate ecosystems in
      northern China. Our results showed a clear pattern of increased microbial biomass
      C to nitrogen (N) ratio in most winter soils. Concurrently, a shift in soil
      microbial community composition occurred with higher fungal to bacterial biomass
      ratio and gram negative (G-) to gram positive (G+) bacterial biomass ratio in
      winter than in summer. Furthermore, potential SOC mineralization rate was higher
      in winter than in summer. Our study demonstrated a distinct transition of
      microbial community structure and function from winter to summer in temperate
      snow-covered ecosystems. Microbial N immobilization in winter may not be the
      major contributor for plant growth in the following spring. 

PMID- 24667934
TI  - Catalytic activation of OKO zeolite with intersecting pores of 10- and 12
      membered rings using atomic layer deposition of aluminium.
AB  - Tetrahedral framework aluminium was introduced in all-silica zeolite -COK-14
      using Atomic Layer Deposition (ALD) involving alternating exposure to
      trimethylaluminium and water vapour. The modification causes permanent conversion
      of the originally interrupted framework of -COK-14 to a fully connected OKO type
      framework, and generates catalytic activity in the acid catalysed hydrocarbon
      conversion reaction. 

PMID- 24667931
TI  - FDA's nozzle numerical simulation challenge: non-Newtonian fluid effects and
      blood damage.
AB  - Data from FDA's nozzle challenge-a study to assess the suitability of simulating
      fluid flow in an idealized medical device-is used to validate the simulations
      obtained from a numerical, finite-differences code. Various physiological
      indicators are computed and compared with experimental data from three different
      laboratories, getting a very good agreement. Special care is taken with the
      derivation of blood damage (hemolysis). The paper is focused on the laminar
      regime, in order to investigate non-Newtonian effects (non-constant fluid
      viscosity). The code can deal with these effects with just a small extra
      computational cost, improving Newtonian estimations up to a ten percent. The
      relevance of non-Newtonian effects for hemolysis parameters is discussed. 

PMID- 24667936
TI  - Synthesis of magnetic ion-imprinted composites and selective separation and
      preconcentration of U(VI).
AB  - The U(VI) magnetic ion-imprinted composite (MIIC) with a uniform core-shell
      structure for the selective separation and preconcentration of U(VI) was prepared
      by copolymerization of a ternary complex of uranyl ions with 4-vinylpyridine (4
      VP) and acrylamide in the presence of 2,2'-azobisisobutyronitrile. The sorption
      of U(VI) on the MIIC from aqueous solution was evaluated. The maximum sorption
      capacity of MIIC for U(VI) was 354.85 mg g(-1), which was much higher than that
      of the magnetic nonimprinted composite. The MIIC could be recovered by desorbing
      the U(VI)-loaded MIIC with 0.5 mol L(-1) HNO3, and the surface morphology of MIIC
      after five consecutive sorption/desorption cycles was significantly damaged. The
      competitive sorption experiments showed that the MIIC had a desirable selectivity
      for U(VI) over a range of competing metal ions. The MIIC may be a promising
      sorbent material for the selective separation and preconcentration of U(VI).

PMID- 24667937
TI  - Dynamics of various polymer-graphene interfacial systems through atomistic
      molecular dynamics simulations.
AB  - The current work refers to a simulation study on hybrid polymer-graphene
      interfacial systems. We explore the effect of graphene on the mobility of
      polymers, by studying three well known and widely used polymers, polyethylene
      (PE), polystyrene (PS) and poly(methyl-methacrylate) (PMMA). Qualitative and
      quantitative differences in the dynamical properties of the polymer chains in
      particular at the polymer-graphene interface are detected. Results concerning
      both the segmental and the terminal dynamics render PE much faster than the other
      two polymers; PS follows, while PMMA is the slowest one. Clear spatial dynamic
      heterogeneity has been observed for all model systems, with different dynamical
      behavior of the adsorbed polymer segments. The segmental relaxation time of the
      polymer (tauseg) as a function of the distance from graphene shows an abrupt
      decrease beyond the first adsorption layer for PE, as a result of its well
      ordered layered structure close to graphene, though a more gradual decay is
      observed for PS and PMMA. The distribution of the relaxation times of adsorbed
      segments was also found to be broader than those of the bulk ones for all three
      polymer-graphene systems. 

PMID- 24667935
TI  - Capillary morphogenesis gene 2 inhibits growth of breast cancer cells and is
      inversely correlated with the disease progression and prognosis.
AB  - BACKGROUND: Capillary morphogenesis gene 2 (CMG2) also known as anthrax toxin
      receptor 2 was identified as a gene being up-regulated in capillary
      morphogenesis. It has been shown to be involved in cell adhesion and motility
      which are critical functions for cancerous cells to disseminate. The present
      study aimed to examine the expression of CMG2 in breast cancer and its
      implication in the disease progression. MATERIALS AND METHODS: Breast primary
      tumours and background tissues were collected immediately after surgery and
      stored at -80  degrees C with approval by the local ethics committee, and written
      consent obtained from patients. The expression of CMG2 in 127 breast cancer
      tumour samples and 34 normal mammary tissues was determined using real-time PCR.
      Knockdown and over-expression in breast cancer cells were established using
      constructed plasmid vectors carrying either anti-CMG2 ribozyme or full-coding
      sequence of human CMG2. The effect on growth of breast cancer cells was examined
      using in vitro and in vivo models. RESULTS: The CMG2 transcript levels were
      reduced in advanced tumours compared with its expression in tumours of early
      stage according to their TNM staging. The reduced expression was associated with
      shorter overall survival, p = 0.004 compared with patients who had higher
      expression. The knockdown of CMG2 resulted in an increased in vitro growth of MDA
      MB-231 cells which express this gene at relatively higher levels. This is
      consistent with the finding from MCF-7 cells which express lower levels of CMG2
      and exhibited reduced growth following over-expression of CMG2. The over
      expression of CMG2 also demonstrated an inhibitory effect on in vivo growth of
      MCF-7 cells. CONCLUSION: Reduced expression of CMG2 is associated with disease
      progression and poor prognosis of breast cancer. CMG2 has an inhibitory effect on
      growth of breast cancer cells. Further investigation is required to shed light on
      the prognostic and therapeutic potential of targeting this molecule.

PMID- 24667939
TI  - Accepting transitions: African Americans discuss end of life.
AB  - BACKGROUND: African Americans typically underuse hospice care; this study
      explores their end of life attitudes. METHODS: An iterative focus group strategy
      generated qualitative data using 4 baseline groups and 1 confirmatory focus group
      recruited from predominantly African American churches. Each group consisted of 8
      to 14 adults. Investigators analyzed data for dominant themes, representatives
      from baseline groups returned to discuss the results. RESULTS: A total of 43
      African Americans (male: 8 [18.6]; female: 35 [81.4]) participated in initial
      discussions, with 10 returning for follow-up. The prevailing theme was
      transitions; with life to death dominating discourse; other themes included
      curative to palliative care and acceptance of death as inevitable.
      RECOMMENDATION: Among African Americans, outreach efforts may be strengthened by
      reframing the dying process as the product of many transitions and reaching out
      to faith-based communities.

PMID- 24667938
TI  - Risk behaviors and risk factors for HIV infection among participants in the
      Bangkok tenofovir study, an HIV pre-exposure prophylaxis trial among people who
      inject drugs.
AB  - INTRODUCTION: HIV spread rapidly among people who inject drugs in Bangkok in the
      late 1980s. In recent years, changes in drug use and HIV-associated risk
      behaviors have been reported. We examined data from the Bangkok Tenofovir Study,
      an HIV pre-exposure prophylaxis trial conducted among people who inject drugs, to
      assess participant risk behavior and drug use, and to identify risk factors for
      HIV infection. METHODS: The Bangkok Tenofovir Study was a randomized, double
      blind, placebo-controlled trial. HIV status was assessed monthly and risk
      behavior every 3 months. We used generalized estimating equations logistic
      regression to model trends of injecting, needle sharing, drugs injected,
      incarceration, and sexual activity reported at follow-up visits; and proportional
      hazards models to evaluate demographic characteristics, sexual activities,
      incarceration, drug injection practices, and drugs injected during follow-up as
      predictors of HIV infection. RESULTS: The proportion of participants injecting
      drugs, sharing needles, and reporting sex with more than one partner declined
      during follow-up (p<0.001). Among participants who reported injecting at
      enrollment, 801 (53.2%) injected methamphetamine, 559 (37.1%) midazolam, and 527
      (35.0%) heroin. In multivariable analysis, young age (i.e., 20-29 years) (p =
      0.02), sharing needles (p<0.001), and incarceration in prison (p = 0.002) were
      associated with incident HIV infection. Participants reporting sex with an
      opposite sex partner, live-in partner, casual partner, or men reporting sex with
      male partners were not at a significantly higher risk of HIV infection compared
      to those who did not report these behaviors. CONCLUSION: Reports of HIV
      associated risk behavior declined significantly during the trial. Young age,
      needle sharing, and incarceration were independently associated with HIV
      infection. Sexual activity was not associated with HIV infection, suggesting that
      the reduction in HIV incidence among participants taking daily oral tenofovir
      compared to those taking placebo was due to a decrease in parenteral HIV
      transmission.

PMID- 24667941
TI  - Pseudoaneurysm as a complication of shoulder arthroscopy.
AB  - A case of pseudoaneurysm that is a rare complication of shoulder arthroscopy is
      reported. A 73-year-old man with rotator cuff tear underwent arthroscopic rotator
      cuff repair. On post-operative day 3, a pulsating mass (diameter 5 mm) was
      detected near the anterior portal. Then, the mass gradually enlarged, which was
      diagnosed as pseudoaneurysm. After the consultation with vascular surgeons, the
      mass was surgically excised following ligation of feeding artery 6 weeks after
      the arthroscopic surgery. Thus far, no recurrence has been observed. Level of
      evidence V.

PMID- 24667940
TI  - Outcome of anatomical double-bundle ACL reconstruction using hamstring tendons
      via an outside-in approach.
AB  - PURPOSE: To evaluate the clinical outcome of anatomical double-bundle anterior
      cruciate ligament (ACL) reconstruction using multistranded hamstring tendons via
      an outside-in approach. METHODS: One hundred and twenty-one patients (mean age 28
      +/- 10 years) who underwent ACL reconstruction were examined. Using an outside-in
      femoral drill guide, an upper femoral tunnel for the anteromedial (AM) graft was
      created just below the superior articular cartilage margin of the medial wall of
      the lateral condyle through a small incision. A lower femoral tunnel for the
      posterolateral (PL) graft was drilled in the centre of the inferior-posterior
      half of the attachment area behind the resident's ridge in the same manner. Two
      tibial tunnels were created at the centre of the AM and PL bundle footprints of a
      normal ACL. Patients were evaluated at 24 months postoperatively. RESULTS:
      According to the IKDC form, 52 knees (43 %) were graded as normal, 64 (53 %) as
      nearly normal, 1 (1 %) as abnormal and 4 (3 %) as graft rupture due to re-injury.
      Loss of knee extension of <5 degrees  was observed in one patient (1 %). Among
      111 patients who were directly evaluated, none showed loss of flexion of <5
      degrees . Lachman sign was negative in 103 patients (93 %), while the pivot shift
      test result was negative or equivalent to that of the contralateral healthy knee
      in 103 patients (93 %). The mean side-to-side difference in anterior laxity at
      manual maximum force with the KT-2000 arthrometer((r)) was 0.9 +/- 1.1 mm, and 94
      % of patients showed a range between -1 and +2 mm. CONCLUSION: The anatomical
      double-bundle outside-in ACL reconstruction provided a satisfactory short-term
      outcome. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 24667942
TI  - Biomechanical comparison of rotational activities between anterior cruciate
      ligament- and posterior cruciate ligament-reconstructed patients.
AB  - PURPOSE: The purpose of this study was to compare the early functional recovery
      using biomechanical properties between anterior cruciate ligament (ACL)- and
      posterior cruciate ligament (PCL)-reconstructed patients and to determine the
      biomechanical deficit of PCL-reconstructed patients compared to ACL-reconstructed
      patients. METHODS: A motion analysis system was used to measure and calculate
      kinematic and kinetic data for 10 patients who underwent PCL-reconstructed
      patients [experimental group (group 1)], 10 ACL-reconstructed patients (group 2),
      and 10 healthy subjects (group 3) during 45 degrees , 90 degrees , 135 degrees ,
      and 180 degrees  cutting and turn running tasks. Groups 1 and 2 were assessed at
      3 (return to daily activity) and 6 months (return to light sports)
      postoperatively. RESULTS: At 3 months postoperatively, compared to groups 2 and
      3, group 1 showed a decrease in knee flexion angle, extension moment, valgus
      moment, external rotational moment, ground reaction force, and increased
      hamstring-quadriceps ratio. At 6 months postoperatively, results from group 1
      resembled those of groups 2 and 3 over time. CONCLUSIONS: Patients who underwent
      PCL reconstruction showed some biomechanical deficits in performance of
      activities requiring rotation, compared to those who underwent ACL
      reconstruction. Therefore, the modification of a rehabilitation programme for
      patients who underwent PCL reconstruction would be necessary for improvement of
      the biomechanical properties during performance of dynamic activities. LEVEL OF
      EVIDENCE: Case-control study, Level III.

PMID- 24667943
TI  - Novel evidence that crosstalk between the complement, coagulation and
      fibrinolysis proteolytic cascades is involved in mobilization of hematopoietic
      stem/progenitor cells (HSPCs).
AB  - The role of blood proteinases in the mobilization of hematopoietic
      stem/progenitor cells (HSPCs) is still not well understood. As previously
      reported, activation of the complement cascade (ComC) and cleavage of C5 by C5
      convertase are enabling events in the release of C5a that plays a crucial role in
      the egress of HSPCs from bone marrow (BM) into peripheral blood (PB) and explains
      why C5-deficient mice are poor mobilizers. Here we provide evidence that during
      granulocyte colony-stimulating factor- and AMD3100-induced mobilization, not only
      the ComC but also two other evolutionarily ancient proteolytic enzyme cascades,
      the coagulation cascade (CoaC) and the fibrynolytic cascade (FibC), become
      activated. Activation of all three cascades was measured by generation of C5a,
      decrease in prothrombin time and activated partial thromboplastin time as well as
      an increase in the concentrations of plasmin/antiplasmin and
      thrombin/antithrombin. More importantly, the CoaC and FibC, by generating
      thrombin and plasmin, respectively, provide C5 convertase activity, explaining
      why mobilization of HSPCs in C3-deficient mice, which do not generate ComC
      generated C5a convertase, is not impaired. Our observations shed more light on
      how the CoaC and FibC modulate stem cell mobilization and may lead to the
      development of more efficient mobilization strategies in poor mobilizers.
      Furthermore, as it is known that all these cascades are activated in all the
      situations in which HSPCs are mobilized from BM into PB (for example, infections,
      tissue/organ damage or strenuous exercise) and show a circadian rhythm of
      activation, they must be involved in both stress-induced and circadian changes in
      HSPC trafficking in PB.

PMID- 24667945
TI  - Ethmoidal dural arteriovenous fistula with unusual drainage route treated by
      transarterial embolization.
AB  - Ethmoidal dural arteriovenous fistulas (AVFs) are rare intracranial lesions
      associated with a high risk of intracranial hemorrhage. In particular, this
      entity with reflux drainage directly into the ophthalmic vein is extremely rare.
      We report a case of ethmoidal dural AVF with direct drainage of the superior
      ophthalmic vein (SOV) and inferior ophthalmic vein (IOV), successfully treated by
      endovascular surgery. A 58-year-old man presented with progressive diplopia.
      Angiography and contrast-enhanced CT showed an ethmoidal dural AVF supplied via
      the bilateral anterior ethmoidal arteries and venous drainage through the left
      SOV and IOV. A transarterial approach through the bilateral anterior ethmoidal
      arteries was used to place the microcatheter close to the fistula site. After
      intra-arterial embolization with 20% N-butyl cyanoacrylate, the dural AVF was
      completely occluded. In patients with good vascular access, endovascular
      transarterial embolization may be an effective and less invasive treatment
      strategy for ethmoidal dural AVF. 

PMID- 24667944
TI  - Predictors of mean arterial pressure morning rate of rise and power function in
      subjects undergoing ambulatory blood pressure recording.
AB  - BACKGROUND: We determined clinical predictors of the rate of rise (RoR) in blood
      pressure in the morning as well as a novel measure of the power of the BP surge
      (BP(power)) derived from ambulatory blood pressure recordings. METHODS: BP(power)
      and RoR were calculated from 409 ambulatory blood pressure (ABP) recordings from
      subjects attending a cardiovascular risk clinic. Anthropometric data, blood
      biochemistry, and history were recorded. The 409 subjects were 20-82 years old
      (average 57, SD = 13), 46% male, 9% with hypertension but not on medication and
      34% on antihypertensive medication. RESULTS: Average RoR was 11.1 mmHg/hour (SD =
      8) and BP(power) was 273 mmHg(2)/hour (SD = 235). Only cholesterol, low density
      lipoprotein and body mass index (BMI) were associated with higher BP(power) and
      RoR (P<0.05) from 25 variables assessed. BP(power) was lower in those taking beta
      blockers or diuretics. Multivariate analysis identified that only BMI was
      associated with RoR (4.2% increase/unit BMI, P = 0.020) while cholesterol was the
      only remaining associated variable with BP(power) (17.5% increase/mmol/L
      cholesterol, P = 0.047). A follow up of 213 subjects with repeated ABP after an
      average 1.8 years identified that baseline cholesterol was the only predictor for
      an increasing RoR and BP(power) (P<0.05). 37 patients who commenced statin
      subsequently had lower BP(power) whereas 90 age and weight matched controls had
      similar BP(power) on follow-up. CONCLUSIONS: Cholesterol is an independent
      predictor of a greater and more rapid rise in morning BP as well as of further
      increases over several years. Reduction of cholesterol with statin therapy is
      very effective in reducing the morning blood pressure surge.

PMID- 24667946
TI  - Not your typical torticollis: a case of atlantoaxial rotatory subluxation.
AB  - A 9-year-old boy was pushed while carrying a heavy backpack. He had no fall or
      direct trauma to his neck. After a few hours from the incident, he presented with
      neck pain and torticollis. However, somewhat atypical for torticollis, he was not
      able to rotate his face to the neutral position. There were no neurological
      deficits. Concerned by his inability to rotate his neck, the clinician suggested
      CT of the upper cervical spine, which demonstrated rotary subluxation of the
      atlantoaxial junction. The patient was taken to the operating theatre. Reduction
      was performed under general anaesthesia. He did well and was back to school in
      the following days. 

PMID- 24667948
TI  - Kikuchi-Fujimoto's disease with abdominal pain due to intra-abdominal
      lymphadenitis.
AB  - A 29-year-old woman was admitted to our hospital with fever and abdominal pain.
      Abdominal echogram and CT revealed intra-abdominal lymphadenopathy. Seven days
      after the onset, she developed cervical lymphadenitis. Kikuchi-Fujimoto's disease
      (KFD) was diagnosed on cervical lymph node biopsy. Although KFD with intra
      abdominal lymphadenopathy is rare, it should be considered in young adults with
      intra-abdominal lymphadenitis. Because KFD is a benign, self-limiting disease, we
      suggest the use of a minimally invasive method of diagnosis such as superficial
      lymph node biopsy. 

PMID- 24667947
TI  - Small cell lung carcinoma presenting as a caecal polyp on surveillance
      colonoscopy.
AB  - A 60-year-old man underwent surveillance colonoscopy that demonstrated five
      subcentimetre polyps, all of which were biopsied. One of the five polyps had
      histopathology consistent with small cell lung carcinoma (SCLC) metastasis from
      primary lung cancer. Subsequent imaging demonstrated a spiculated mass in the
      right upper lung lobe with metastasis to the brain, liver and spleen. He was
      immediately treated with palliative whole-brain irradiation followed by eight
      cycles of carboplatin and etoposide. Despite aggressive management, he had
      disease progression characterised by worsening performance status and development
      of transfusion-dependent anaemia, new blastic bone lesions and epidural disease.
      Given his liver failure, he was not considered a candidate for second-line
      topotecan. After discussion with the patient, family and palliative services, he
      was discharged with home hospice. This report describes a rare case of advanced
      SCLC presenting as a metastatic caecal polyp on surveillance colonoscopy. 

PMID- 24667949
TI  - An 8-year-old girl with congenital deafness and musculoskeletal abnormalities.

PMID- 24667950
TI  - Fever in the returning child traveller: approach to diagnosis and management.
AB  - During the last half century there has been an exponential increase in
      international travel including to more exotic and long-haul destinations. The
      assessment of febrile returning child travellers presents diagnostic challenges
      and is often performed poorly. A detailed travel and medical history, clinical
      examination and appropriate first-line investigations are essential. While the
      majority of children will have a common self-limiting or easily treatable
      infection, it is important to consider other causes, including imported
      infections, which may be life-threatening or highly contagious. In this article,
      we provide guidance on the initial assessment and management of such children
      with a focus on some of the more important imported infections, including
      malaria, dengue, typhoid fever, travellers' diarrhoea, respiratory infections,
      tuberculosis, schistosomiasis and rickettsial diseases.

PMID- 24667951
TI  - Developing Culturally Targeted Diabetes Educational Materials for Older Russian
      Speaking Immigrants.
AB  - PURPOSE: Older adults who immigrate late in life face many challenges adapting to
      a new country. Immigrants bring their cultural beliefs and behaviors with them,
      which can influence their ability to make dietary changes required when they have
      type 2 diabetes. Culturally targeted patient education materials are needed to
      improve immigrants' health literacy and abilities to self-manage diabetes.
      Currently, there is a scarcity of diabetes patient education materials to meet
      the educational needs of the Russian-speaking immigrant group. The purpose of
      this article is to describe a project in which culturally targeted diabetes
      education materials for older Russian-speaking immigrants were designed and
      developed. CONCLUSIONS: Culturally targeted patient education materials are
      essential if they are to be accepted and used by clients from different ethnic
      minority populations. The creation of culturally relevant materials requires a
      team effort and community stakeholder input. The availability of materials on the
      internet facilitates access and use by health care providers. Culturally targeted
      education materials are an important component in addressing health literacy in
      ethnic minority populations. Next steps require that these materials be evaluated
      to test their impact on diabetes self-management behaviors and clinical outcomes
      such as adherence, amount of physical activity, and blood glucose levels.

PMID- 24667953
TI  - From the guest editor: The rise of CAR therapy: the CD19 paradigm, and beyond.
      Introduction.

PMID- 24667952
TI  - Treatment of small cell lung cancer in academic and community settings: factors
      associated with receiving standard therapy and survival.
AB  - PURPOSE: Small cell lung cancer (SCLC) historically has had poor prognosis.
      Clinical trials have demonstrated improved survival among patients receiving
      standard platinum-/etoposide-based chemotherapy. Whereas treatment patterns and
      outcomes have been evaluated for patients with SCLC in clinical trials,
      population-based practice patterns are not well known. METHODS: The National
      Cancer Institute's Patterns of Care study was used to evaluate patient and
      provider factors associated with standard treatment, clinical trial enrollment,
      and 12-month relative hazard of death. RESULTS: Among 931 patients with SCLC
      diagnosed in 2007 in academic and community settings, 72.2% of patients with
      limited-stage (LS) disease received chemoradiation and 42.2% of patients with
      extensive-stage (ES) disease received chemotherapy only; the expected treatment
      scenarios by stage. Less than 1% of the patients enrolled in clinical trials and
      2.1% of the patients with LS disease and 3.4% of the patients with ES disease
      refused any type of treatment. Patients 80 years or older at diagnosis and those
      with pneumonia/lung collapse were less likely to receive chemoradiation for LS
      disease. Patients treated in hospitals with residency programs were more likely
      to receive chemotherapy for ES disease, and patients 80 years or older were less
      likely to receive chemotherapy for ES disease. Finally, female patients with LS
      disease, black patients with ES disease, and all patients who received
      chemotherapy compared to receiving radiation alone or no therapy experienced
      significantly lower mortality. DISCUSSION: Despite the demonstrated lower
      mortality, a relatively large proportion of patients with SCLC are not treated
      with a standard treatment regimen. Future studies should evaluate efforts to
      promote use of appropriate treatment regimens and encourage clinical trial
      participation.

PMID- 24667954
TI  - CD19CAR T cells: From humble beginnings to cancer immunotherapy's poster child.
AB  - The conceptual foundation and technical evolution of T-cell genetic engineering
      for the purpose of retargeting antigen specificity as a clinical immunotherapy
      modality in oncology have been decades in the making, with many laboratories
      providing important contributions to overall progress. The development of the
      component parts of this technology has required the amalgamation of divergent
      scientific disciplines including cellular immunology, lymphocyte signaling
      biology, molecular biology, vector virology, and practical improvements in T-cell
      culture systems. Together with advances in the understanding of clinical
      variables that facilitate persistent engraftment and expansion of adoptively
      transferred T cells, the field of CD19CAR research evolved as a logical venue for
      revealing proof-of-principle clinical antitumor activity. Indeed, the modality
      has definitively crossed the threshold from a preclinical model system to a
      therapeutic approach with demonstrable potent antileukemic efficacy in patients
      harboring advanced and refractory leukemias. The dramatic responses seen in
      CD19CAR T-cell clinical trials from multiple institutions does not signal an end
      to the evolution of CD19CAR T cells, as along with early clinical successes, new
      challenges have emerged that require further refinement of this nascent
      therapeutic platform. 

PMID- 24667955
TI  - CD19-CAR trials.
AB  - CD19 is a B-lineage-specific transmembrane glycoprotein, the expression of which
      is maintained on more than 95% B-cell malignancies. This strict lineage
      restriction makes CD19 an ideal target for immune therapies using chimeric
      antigen receptors (CARs). Here, we review published phase 1 trials of T cells
      expressing CARs targeting CD19 and describe briefly the biological questions that
      they addressed. All patients treated in these trials had relapsed B-cell
      malignancies, which in many cases were chemorefractory. Nonetheless, major
      responses have been observed, especially in patients with chronic lymphocytic
      leukemia and acute lymphoblastic leukemia. Many of these responses were
      accompanied by a systemic inflammatory reaction syndrome that could be life
      threatening but was almost always reversible with adequate medical management.
      Given their remarkable activity, CD19-CAR T cells are likely to be quickly
      incorporated into the management of B-cell neoplasms; these cells have become the
      paradigm for similar strategies targeting other cancers. 

PMID- 24667956
TI  - Managing cytokine release syndrome associated with novel T cell-engaging
      therapies.
AB  - Chimeric antigen receptor (CAR)-modified T cells and bispecific T cell-engaging
      antibodies have demonstrated dramatic clinical responses in recent clinical
      trials. The hallmark of these novel highly active immunotherapies is
      nonphysiologic T cell activation, which has correlated not only with greatly
      increased efficacy but also with notable toxicity in some cases. We and others
      have observed a cytokine release syndrome (CRS), which correlates with both
      toxicity and efficacy in patients receiving T cell-engaging therapies. In
      addition to elevations in effector cytokines, such as interferon-gamma, cytokines
      associated with hemophagocytic lymphohistiocytosis or macrophage activation
      syndrome, such as interleukin (IL)-10 and IL-6, may also be markedly elevated.
      Whereas corticosteroids may control some of these toxicities, their potential to
      block T cell activation and abrogate clinical benefit is a concern. Detailed
      studies of T cell proliferation and the resultant immune activation produced by
      these novel therapies have led to more targeted approaches that have the
      potential to provide superior toxicity control without compromising efficacy. One
      approach we have developed targets IL-6, a prominent cytokine in CRS, using the
      IL-6R antagonist tocilizumab. We will review the pathophysiology and management
      options for CRS associated with T cell-engaging therapies. 

PMID- 24667957
TI  - The emergence of T-bodies/CAR T cells.
AB  - The nickname "T-body" is used to denote a T cell expressing an antigen-specific
      or antibody-based chimeric receptor that combines antibody specificity with T
      cell effector or regulatory function. Initially, we designed and constructed
      chimeric antibody-based receptors and expressed them in T cells to study the role
      of major histocompatibility complex in triggering T-cell activation. To this end,
      we replaced both variable domains (Valpha and Vbeta of the native T-cell receptor
      chains) with antibody-derived VH and VL sequences. After transfection into T
      cells, the 2 chimeric chains paired, associated with the CD3 complex, and endowed
      transfectants with non-major histocompatibility complex-restricted antibody type
      specificity. In subsequent studies, we developed next generation of chimeric
      antibody-based receptors by fusing an antibody single-chain variable fragment to
      T-cell activation motifs. This modular configuration simplified gene transfer,
      avoided mixed pairing with endogenous T-cell receptor chains, and enabled
      simultaneous insertion of various domains as costimulatory moieties to generate T
      bodies with efficient antitumor reactivity.

PMID- 24667958
TI  - CD28z CARs and armored CARs.
AB  - CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested
      in the clinic with very promising outcomes. However, limitations to CAR T cell
      therapy exist. These include lack of efficacy against some tumors, specific
      targeting of tumor cells without affecting normal tissue and retaining activity
      within the suppressive tumor microenvironment. Whereas promising clinical trials
      are in progress, preclinical development is focused on optimizing CAR design, to
      generate "armored CAR T cells," which are protected from the inhibitory tumor
      microenvironment. Studies investigating the expression of cytokine transgenes,
      combination therapy with small molecule inhibitors, or monoclonal antibodies, are
      aimed at improving the antitumor efficacy of CAR T cell therapy. Other strategies
      aimed at improving CAR T cell therapy include using dual CARs and chemokine
      receptors to more specifically target tumor cells. This review will describe the
      current clinical data and some novel armored CAR T cell approaches for improving
      antitumor efficacy therapy. 

PMID- 24667959
TI  - 4-1BB chimeric antigen receptors.
AB  - In addition to T-cell receptor signals, T lymphocytes require costimulatory
      signals for robust activation. Among these, those mediated by 4-1BB (CD137,
      TNFRSF9) are critical for tumor immunity. 4-1BB is expressed in T-cell receptor
      activated lymphocytes as well as natural killer cells and other hematopoietic and
      nonhematopoietic cells. 4-1BB ligation induces a signaling cascade that results
      in cytokine production, expression of antiapoptotic molecules, and enhanced
      immune responses. In line with the described function of 4-1BB, its addition to
      CD3zeta chimeric antigen receptors (CARs) increases their capacity to provoke T
      cell expansion and antitumor activity. The results of preclinical studies with 4
      1BB CARs have been corroborated by encouraging results from clinical trials.
      Advantages and disadvantages of 4-1BB CARs versus CARs bearing other
      costimulatory components remain to be fully elucidated. In this review, we
      discuss the properties of 4-1BB, the design of 4-1BB CARs, and the function of T
      lymphocytes and natural killer cells expressing them. 

PMID- 24667960
TI  - Adoptive therapy with chimeric antigen receptor-modified T cells of defined
      subset composition.
AB  - The ability to engineer T cells to recognize tumor cells through genetic
      modification with a synthetic chimeric antigen receptor has ushered in a new era
      in cancer immunotherapy. The most advanced clinical applications are in targeting
      CD19 on B-cell malignancies. The clinical trials of CD19 chimeric antigen
      receptor therapy have thus far not attempted to select defined subsets before
      transduction or imposed uniformity of the CD4 and CD8 cell composition of the
      cell products. This review will discuss the rationale for and challenges to using
      adoptive therapy with genetically modified T cells of defined subset and
      phenotypic composition. 

PMID- 24667961
TI  - Genetic modification of T cells.
AB  - Gene transfer technology has advanced rapidly from simple physical-chemical
      laboratory methods in the 1970s and 1980s to the sophisticated viral and nonviral
      methods currently in clinical practice. Herein, we review 4 gene transfer
      methodologies applied in human gene therapy clinical trials transferring chimeric
      antigen receptors into T cells for the treatment of B-cell malignancies. The 4
      methods include 2 viral vector gene transfer technologies, gamma retroviral
      vectors and lentiviral vectors, and 2 nonviral methods, transposons and mRNA
      electroporation. 

PMID- 24667962
TI  - CAR T cells for solid tumors: armed and ready to go?
AB  - Chimeric antigen receptor (CAR) T cells face a unique set of challenges in the
      context of solid tumors. To induce a favorable clinical outcome, CAR T cells have
      to surmount a series of increasingly arduous tasks. First, they have to be made
      specific for an antigen whose expression clearly demarcates tumor from normal
      tissue. Then, they must be able to home and penetrate the desmoplastic stroma
      that surrounds the tumor. Once within the tumor, they must expand, persist, and
      mediate cytotoxicity in a hostile milieu largely composed of immunosuppressive
      modulators. Whereas a seemingly herculean task, all of the aforementioned
      requirements can potentially be met effectively through both intrinsic and/or
      extrinsic modifications of CAR T cells. In this review, we delineate the barriers
      imposed by solid tumors on CARs and strategies that have and should be undertaken
      to improve therapeutic response. 

PMID- 24667963
TI  - NKG2D CARs as cell therapy for cancer.
AB  - The NKG2D cell receptor and its ligands have attracted considerable interest as a
      potential strategy to attack tumor cells. NKG2D ligands are expressed on most
      types of tumors, and they demonstrate relative selectivity of ligand expression
      on tumor cells compared to healthy cells. Several different variants of NKG2D
      based chimeric antigen receptors (CARs) have been developed, and extensive in
      vivo mechanistic studies performed demonstrated that cytotoxicity and cytokines
      are important for the efficacy NKG2D CAR adoptive T-cell therapy. NKG2D CARs
      target tumor cells, and they also target immunosuppressive cells within the tumor
      microenvironment. Under certain conditions, NKG2D ligand expression can be found
      on nontumor tissue, so potential off-tumor toxicity remains. In this article, we
      review the use of NKG2D as a basis for CAR targeting of tumors. 

PMID- 24667964
TI  - Novel approaches to enhance the specificity and safety of engineered T cells.
AB  - T-cell therapies using engineered T cells show great promise for cancer
      immunotherapy, as illustrated by the CD19 paradigm. Much of the excitement about
      this approach, and second-generation CARs in particular, is due to the dramatic
      clinical results recently reported by a few centers, especially in acute
      lymphoblastic leukemia, and the applicability of this approach, in principle, to
      a wide range of cancers. Extending the use of CAR therapies to cancers other than
      B-cell malignancies will require selective tumor targeting with minimal or
      acceptable "on-target, off-tumor" effects. The identification of new CAR target
      antigens is thus one of the next big challenges to address. Recognizing the
      paucity of currently available tumor-specific targets, we have developed broadly
      applicable approaches to enhance the tumor selectivity and safety of engineered T
      cells. Here, we review 2 promising concepts. One is to improve tumor targeting
      based on combinatorial antigen recognition. The other uses receptors that provide
      antigen-specific inhibition, which we named iCARs, to divert T cells from the
      normal tissues one wants to protect. 

PMID- 24667965
TI  - Platinum catalyzed sequential hydroboration of decaborane: a facile approach to
      poly(alkenyldecaborane) with decaborane in the mainchain.
AB  - Catalytic sequential hydroboration of decaborane for the synthesis of
      poly(organodecaborane), with decaborane in the mainchain, is reported for the
      first time. Under a platinum catalytic system, poly(6-hexenyldecaborane) and
      poly(6-norbornenyldecaborane) are obtained with well-defined structures and a
      moderate yield. Thermogravimetric analysis demonstrates that the char yields are
      73% and 82%, respectively. 

PMID- 24667966
TI  - Characterization and mutational analysis of omega-class GST (GSTO1) from Apis
      cerana cerana, a gene involved in response to oxidative stress.
AB  - The Omega-class of GSTs (GSTOs) is a class of cytosolic GSTs that have specific
      structural and functional characteristics that differ from those of other GST
      groups. In this study, we demonstrated the involvement of the GSTO1 gene from A.
      cerana cerana in the oxidative stress response and further investigated the
      effects of three cysteine residues of GSTO1 protein on this response. Real-time
      quantitative PCR (qPCR) showed that AccGSTO1 was highly expressed in larvae and
      foragers, primarily in the midgut, epidermis, and flight muscles. The AccGSTO1
      mRNA was significantly induced by cold and heat at 1 h and 3 h. The TBA (2
      Thiobarbituric acid) method indicated that cold or heat resulted in MDA
      accumulation, but silencing of AccGSTO1 by RNAi in honeybees increased the
      concentration of MDA. RNAi also increased the temperature sensitivity of
      honeybees and markedly reduced their survival. Disc diffusion assay indicated
      that overexpression of AccGSTO1 in E. coli caused the resistance to long-term
      oxidative stress. Furthermore, AccGSTO1 was active in an in vitro DNA protection
      assay. Mutations in Cys-28, Cys-70, and Cys-124 affected the catalytic activity
      and antioxidant activity of AccGSTO1. The predicted three-dimensional structure
      of AccGSTO1 was also influenced by the replacement of these cysteine residues.
      These findings suggest that AccGSTO1 plays a protective role in the response to
      oxidative stress. 

PMID- 24667967
TI  - Dual stereocontrol over the Henry reaction using a light- and heat-triggered
      organocatalyst.
AB  - Here we present a novel dynamic organocatalyst, based on a first-generation
      molecular motor core, able to control the stereochemical outcome of the Henry
      reaction using both light and heat as external stimuli. 

PMID- 24667970
TI  - One-step formation of responsive "dumbbell" nanoparticle dimers via quasi-two
      dimensional polymer single crystals.
AB  - We present a facile approach to synthesize "dumbbell" nanoparticle dimers via one
      step coupling of nanoparticles and quasi-two-dimensional polymer single crystals.
      These dimers exhibit responsive properties enabled by flexible polymeric linkers.

PMID- 24667968
TI  - Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in
      genetically-engineered murine models of high-risk neuroblastoma.
AB  - The early identification of children presenting ALK(F1174L)-mutated
      neuroblastoma, which are associated with resistance to the promising ALK
      inhibitor crizotinib and a marked poorer prognosis, has become a clinical
      priority. In comparing the radiology of the novel Th-ALK(F1174L)/Th-MYCN and the
      well-established Th-MYCN genetically-engineered murine models of neuroblastoma
      using MRI, we have identified a marked ALK(F1174L)-driven vascular phenotype. We
      demonstrate that quantitation of the transverse relaxation rate R2* (s(-1)) using
      intrinsic susceptibility-MRI under baseline conditions and during hyperoxia, can
      robustly discriminate this differential vascular phenotype, and identify MYCN
      driven tumors harboring the ALK(F1174L) mutation with high specificity and
      selectivity. Intrinsic susceptibility-MRI could thus potentially provide a non
      invasive and clinically-exploitable method to help identifying children with MYCN
      driven neuroblastoma harboring the ALK(F1174L) mutation at the time of diagnosis.

PMID- 24667971
TI  - Clinically isolated syndrome presenting as paroxysmal dysarthria: a rare but
      typical presentation.

PMID- 24667972
TI  - Reduced Warburg effect in cancer cells undergoing autophagy: steady- state 1H-MRS
      and real-time hyperpolarized 13C-MRS studies.
AB  - Autophagy is a highly regulated, energy dependent cellular process where
      proteins, organelles and cytoplasm are sequestered in autophagosomes and digested
      to sustain cellular homeostasis. We hypothesized that during autophagy induced in
      cancer cells by i) starvation through serum and amino acid deprivation or ii)
      treatment with PI-103, a class I PI3K/mTOR inhibitor, glycolytic metabolism would
      be affected, reducing flux to lactate, and that this effect may be reversible. We
      probed metabolism during autophagy in colorectal HT29 and HCT116 Bax knock-out
      cells using hyperpolarized (13)C-magnetic resonance spectroscopy (MRS) and steady
      state (1)H-MRS. 24 hr PI103-treatment or starvation caused significant reduction
      in the apparent forward rate constant (k(PL)) for pyruvate to lactate exchange
      compared with controls in HT29 (100 MUM PI-103: 82%, p = 0.05) and HCT116 Bax-ko
      cells (10 MUM PI-103: 53%, p = 0.05; 20 MUM PI-103: 42%, p<0.0001; starvation:
      52%, p<0.001), associated with reduced lactate excretion and intracellular
      lactate in all cases, and unchanged lactate dehydrogenase (LDH) activity and
      increased NAD+/NADH ratio following PI103 treatment or decreased LDH activity and
      unchanged NAD+/NADH ratio following starvation. After 48 hr recovery from PI103
      treatment, k(PL) remained below control levels in HT29 cells (74%, p = 0.02), and
      increased above treated values, but remained below 24 hr vehicle-treated control
      levels in HCT116 Bax-ko cells (65%, p = 0.004) both were accompanied by sustained
      reduction in lactate excretion, recovery of NAD+/NADH ratio and intracellular
      lactate. Following recovery from starvation, k(PL) was significantly higher than
      24 hr vehicle-treated controls (140%, p = 0.05), associated with increased LDH
      activity and total cellular NAD(H). Changes in k(PL) and cellular and excreted
      lactate provided measureable indicators of the major metabolic processes
      accompanying starvation- and drug-induced autophagy. The changes are reversible,
      returning towards and exceeding control values on cellular recovery, which
      potentially identifies resistance. k(PL) (hyperpolarized (13)C-MRS) and lactate
      ((1)H-MRS) provide useful biomarkers for the autophagic process, enabling non
      invasive monitoring of the Warburg effect.

PMID- 24667973
TI  - The quantitative and functional changes of NK cells in mice infected with
      Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis is a neurotropic parasite which can cause injury to
      central nervous system and eosinophilic meningitis to human. Natural killer (NK)
      cells are specialized innate lymphocytes important in early defense against
      pathogens as in a variety of intracellular bacterial, viral, and protozoan
      infections. However, the number and function of NK cells in extracellular
      parasitic infection of A. cantonensis are unclear. In this study, on A.
      cantonensis infected mice which may mimic the human's infection, we found that
      the percentage of splenic NK cells and the absolute number of peripheral blood NK
      cells were decreased at 21-day post infection compared with that of controls.
      When administrating with albendazole treatment at early stage of the infection,
      the changes of NK cells could be avoided. Further analysis confirmed that the
      reduction of NK cells was due to their apoptosis manifested as increased
      expressions of annexin V and activated caspase-3 after 16-day post infection.
      Moreover, both activated and inhibitory receptors such as CD16, CD69, NKG2D, and
      Ly49a on NK cells were down-regulated after 16-day post infection. Interestingly,
      NK cells isolated from mice of 21-day post infection showed enhanced IFN-gamma
      production when stimulated with IL-12 for 24 h and cytotoxicity to YAC-1 cells,
      as well as elevated CD107a expression. It is evident that NK cell population and
      its function were changed in A. cantonensis infected mice, suggesting their
      involvement in pathogenesis of the infection. 

PMID- 24667975
TI  - Electrochemical synthesis of a gold atomic cluster-chitosan nanocomposite film
      modified gold electrode for ultra-trace determination of mercury.
AB  - Gold atomic cluster based nanocomposites are important in the field of energy and
      sensing applications due to their interesting optical, electronic, chemical and
      catalytic properties. In the present study a chitosan stabilized gold atomic
      cluster nanocomposite was synthesised by a simple electrochemical technique based
      on the anodic dissolution of a gold electrode in the presence of a cationic
      surfactant, cetyl trimethyl ammonium bromide (CTAB), and a biopolymer, chitosan,
      on a gold electrode. The gold clusters formed were characterized by DLS, TEM,
      MALDI-TOF-MS, XPS, fluorescence and cyclic voltammetry. The developed gold atomic
      cluster-chitosan (AuAC-Chit) nanocomposite modified gold electrode was highly
      sensitive and selective for the electrochemical detection of Hg(ii) ions. It
      offers a wider calibration range of 10(-14)-10(-7) M with a limit of detection
      (LOD) of 0.8 * 10(-14) M and a limit of quantification (LOQ) of 6.6 * 10(-14) M,
      much below the guideline value of 1 * 10(-8) M stipulated by United States
      Environmental Protection Agency (USEPA), accompanied by a good precision of 1.06%
      for 10(-13) M of Hg(ii). The designed sensor is selective to Hg(ii) ions in the
      presence of other coexisting species. 

PMID- 24667974
TI  - Genetic differentiation of invasive Aedes albopictus by RAPD-PCR: implications
      for effective vector control.
AB  - Aedes albopictus is an invasive mosquito species of great concern to public
      health as it is responsible for the biological transmission of several pathogens
      causing dengue, chikungunya, yellow fever, etc. In 2009, this mosquito was
      detected for the first time in Agra City. This study represents the first genetic
      analysis of A. albopictus from India. Random amplified polymorphic DNA (RAPD) was
      used to study the genetic structure of A. albopictus in four populations from
      different larval habitats. Seven RAPD primers produced 141 loci. The results
      displayed rich genetic variation among larval populations which is evident from
      high value of genetic differentiation (G ST), i.e. 0.280, indicating a very great
      genetic differentiation. Effective migration rates were observed to be 1.28,
      depicting a limited gene flow. According to analysis of molecular variance
      (AMOVA), the genetic distance between populations was significant (P < 0.05),
      showing a very high intrapopulation variation (96%) with only 4% variation among
      populations. Average genetic distances between populations were also calculated
      using PopGene software. Nei's average genetic distance between these populations
      was 0.112 (0.05-0.18). The cluster analysis technique of unweighted pair-group
      mean analysis (UPGMA) method of arithmetic averages was used to develop the
      phylogenetic tree which clearly shows two clusters of different larval habitats.
      The findings highlight high genetic differentiation indicating a slight migration
      rate confirming the recent introduction of this species in Agra region.

PMID- 24667976
TI  - Compact structure and non-Gaussian dynamics of ring polymer melts.
AB  - We present a neutron scattering analysis of the structure and dynamics of PEO
      polymer rings with a molecular weight 2.5 times higher than the entanglement
      mass. The melt structure was found to be more compact than a Gaussian model would
      suggest. With increasing time the center of mass (c.o.m.) diffusion undergoes a
      transition from sub-diffusive to diffusive behavior. The transition time agrees
      well with the decorrelation time predicted by a mode coupling approach. As a
      novel feature well pronounced non-Gaussian behavior of the c.o.m. diffusion was
      found that shows surprising analogies to the cage effect known from glassy
      systems. Finally, the longest wavelength Rouse modes are suppressed possibly as a
      consequence of an onset of lattice animal features as hypothesized in theoretical
      approaches. 

PMID- 24667978
TI  - Absorption and efficacy of acetylsalicylic acid in patients with short bowel
      syndrome.
AB  - BACKGROUND: The patients with a short bowel (SB) frequently require antiplatelet
      therapy. Resection of the bowel is likely to modify the absorption and first-pass
      effect of drugs. No data on the absorption and efficacy of the cardiovascular
      dose of aspirin (75-160 mg) in these patients have been published. OBJECTIVE: To
      evaluate the efficacy of a low dose of aspirin in patients with SB caused by
      mesenteric ischemia. METHODS: The efficacy of a low dose of aspirin was assessed
      in 10 consecutive SB patients, both 1 hour and 24 hours after administration
      (peak and trough value, respectively). The primary criterion was the inhibition
      of platelet aggregation, as assessed by light transmission aggregometry,
      triggered with 0.5 mg/mL arachidonic acid. Biological efficacy of aspirin was
      also evaluated by serum thromboxane B2 value and by platelet function analyzer
      100. RESULTS: At its peak value, aspirin had the expected efficacy, as
      demonstrated both by light transmission aggregometry and the other methods.
      However, 24 hours after administration, as many as 30% of patients had lost the
      pharmacological efficacy of their aspirin. CONCLUSION: We show for the first time
      that with at least 30 cm of small intestine, all patients with SB absorb
      sufficient oral aspirin in a cardiovascular dose to rapidly exert the expected
      level of antiplatelet activity. But given only once daily, aspirin does not
      provide stable 24-hour antiplatelet protection in 30% of patients, because of
      increased platelet turnover, as usually observed in patients with extensive
      vascular pathology, diabetes, or inflammation.

PMID- 24667979
TI  - Tetratopic pyrimidine-hydrazone ligands modified with terminal hydroxymethyl and
      acryloyl arms and their Pb(II), Zn(II), Cu(II) and Ag(I) complexes.
AB  - The first tetratopic pyrimidine-hydrazone (pym-hyz) molecular strands containing
      terminal hydroxymethyl (L1) and acryloyl (L2) functional groups have been
      synthesised. L1 was produced by step-wise imine condensation reactions, starting
      with 6-hydroxymethyl-2-pyridinecarboxaldehyde. L2 was then synthesised through
      the treatment of L1 with acryloyl chloride. NMR spectroscopy and X-ray
      crystallography showed that the ligands adopted a helical shape, comprised of 1
      and 1/3 helical turns. Both L1 and L2 uncoiled upon reaction with an excess
      amount of Pb(II), Zn(II) and Cu(II) ions, resulting in linear M4LA8 complexes
      (where M = Pb(II), Zn(II), or Cu(II); L = L1 or L2; and A = ClO4(-), SO3CF3(-) or
      BF4(-)). Horse-shoe shaped Pb2LA4 complexes were also formed by reacting Pb(II)
      ions with either L1 or L2 in a 2 : 1 metal to ligand ratio. The addition of Ag(I)
      ions to either L1 or L2 resulted in Ag2L2A2 double helicates, which were stable
      in the presence of excess Ag(I). The Pb(II), Zn(II) and Ag(I) complexes were
      characterised by NMR spectroscopy, while UV-Vis spectroscopy was used to probe
      the Cu(II) complexes. In addition, X-ray crystallography was used to analyse the
      linear Pb4L1A8, horse-shoe shaped Pb2L1(ClO4)4, twisted Cu3L2(SO3CF3)6, and
      double helicate Ag2L12(SO3CF3)2 complexes yielding the structures
      [Pb4L1(ClO4)7(H2O)]ClO4.4CH3NO2 (1), [Pb4L1(SO3CF3)8]2.6CH3CN.H2O (2),
      [Pb2L1(ClO4)2(CH3CN)(H2O)](ClO4)2.2CH3CN.C4H10O.H2O (3),
      [Cu3L2(SO3CF3)3(CH3CN)2(H2O)](SO3CF3)3.2CH3CN.H2O (4) and
      [Ag2L12](SO3CF3)2.CH3CN.H2O (5), respectively.

PMID- 24667977
TI  - Associations of alcohol consumption and mental health with the prevalence of
      arthritis among US adults: data from the 2012 National Health Interview Survey.
AB  - The findings of association between alcohol consumption and arthritis are mixed
      while little is known about age differences in the associations of mental health
      and behavioral factors with arthritis. This study aimed to estimate the
      prevalence and associated factors of arthritis among US adults using data from
      the 2012 National Health Interview Survey. In total, 8,229 adults with arthritis
      and 26,256 controls were selected from the adult respondents. Weighted univariate
      and multiple logistic regression analyses were used to estimate the odds ratios
      (ORs) with 95 % confidence intervals. The overall prevalence of arthritis was
      22.1 %. The prevalence increased with age (6.8, 29.6, and 47.9 % for 18-49, 50
      64, and 65+ years of age, respectively). The prevalence of mental problems was
      higher in cases than controls [4 vs. 1 % for serious psychological distress
      (SPD), 29 vs. 16 % for anxiety, and 26 vs. 11 % for depression, respectively].
      Multiple logistic regression analyses showed that being female, older age,
      smoking, alcohol consumption, obesity, SPD, depression, and anxiety were
      positively associated with arthritis. Stratified by age, SPD was associated with
      arthritis only in young adults (18-49 years old) while the ORs of anxiety and
      depression with arthritis decreased as age increased. Alcohol consumption
      revealed stronger associations in middle-aged adults and elderly. Using a large
      nationally representative sample in the USA, alcohol consumption, smoking, SPD,
      anxiety, and depression were associated with arthritis, and the associations
      varied across different age groups.

PMID- 24667980
TI  - The role of the delta GABA(A) receptor in ovarian cycle-linked changes in
      hippocampus-dependent learning and memory.
AB  - The delta subunit of the GABAAR is highly expressed in the dentate gyrus of the
      hippocampus where it mediates a tonic extrasynaptic inhibitory current that is
      sensitive to neurosteroids. In female mice, the expression level of the delta
      subunit within the dentate gyrus is elevated in the diestrous relative to estrous
      phase of the estrous cycle. Previous work in our lab found that female delta
      GABAAR KO mice showed enhanced hippocampus-dependent trace but normal hippocampus
      independent delay fear conditioning. Wild-type females in this study showed a
      wide range of freezing levels, whereas delta-GABAAR KO mice expressed only high
      levels of fear. We hypothesized that the variability in the wild-type mice may
      have been due to estrous cycle-mediated changes in the expression of the delta
      GABAAR, with low levels of freezing in mice that were in the diestrous phase when
      dentate gyrus tonic inhibition is high. In the present study we tested this
      hypothesis by utilizing contextual, delay, and trace fear conditioning protocols
      in mice that were trained and tested in either the diestrous or estrous phases.
      Consistent with our hypothesis, we found a significant impairment of hippocampus
      dependent learning and memory during diestrus relative to estrus in wild-type
      mice and this impairment was absent in delta-GABAAR mice. These findings argue
      that the delta-GABAAR plays an important role in estrous cycle-mediated
      fluctuations in hippocampus-dependent learning and memory. 

PMID- 24667982
TI  - Redox-triggered changes in the self-assembly of a ferrocene-peptide conjugate.
AB  - Ultrasonication of a ferrocene conjugate of a short amyloid peptide (Abeta18-20)
      in toluene causes formation of an organogel, which undergoes dramatic structural
      changes upon oxidation from a nanofibrillar network to spherical micelles. This
      morphological change is redox-controlled and reversible. 

PMID- 24667981
TI  - Large conductance calcium-activated potassium channels: their expression and
      modulation of glutamate release from nerve terminals isolated from rat trigeminal
      caudal nucleus and cerebral cortex.
AB  - Large conductance, calcium-activated potassium channels [big potassium (BK)
      channel] consist of a tetramer of pore-forming alpha-subunit and distinct
      accessory beta-subunits (beta1-4) that modify the channel's properties. In this
      study, we analyzed the effects of BK channel activators and blockers on glutamate
      and gamma-aminobutyric acid (GABA) release from synaptosomes isolated from the
      cerebral cortices or trigeminal caudal nuclei (TCN) of rats. Real-time polymerase
      chain reaction was used to characterize BK channel alpha and beta(1-4) subunit
      expression in the cortex and in the trigeminal ganglia (TG), whose neurons
      project primary terminal afferents into the TCN. Immunocytochemistry was used to
      localize these subunits on cortical and TCN synaptosomes. The BK channels
      regulating [(3)H]D-aspartate release from primary afferent nerve terminals
      projecting into the TCN displayed limited sensitivity to iberiotoxin, whereas
      those expressed on cortical synaptosomes were highly sensitive to this toxin. BK
      channels did not appear to be present on GABAergic nerve terminals from the TCN
      since [(3)H]-gamma-aminobutyric acid release in this model was unaffected by BK
      channel activators or blockers. Gene expression studies revealed expression
      levels of the alpha subunit in the TG that were only 31.2 +/- 2.1% of those found
      in cortical tissues. The beta4 subunit was the accessory subunit expressed most
      abundantly in both the cortex and TG. Levels of beta1 and beta2 were low in both
      these areas although beta2 expression in the TG was higher than that found in the
      cortex. Immunocytochemistry experiments showed that co-localization of alpha and
      beta4 subunits (the accessory subunit most abundantly expressed in both brain
      areas) was more common in TCN synaptosomes than in cortical synaptosomes. On the
      basis of these findings, it is reasonable to hypothesize that BK channels
      expressed on glutamatergic terminals in the TCN and cortex have distinct
      pharmacological profiles, which probably reflect different alpha and beta subunit
      combinations. Channels in the cortex seem to be composed mainly of alpha subunits
      and to a lesser degree by alpha and beta4 subunits, whereas in the TG the alpha +
      beta4 combination seems to prevail (although alpha and/or alpha + beta2 channels
      cannot be excluded). In light of the BK channels' selective control of excitatory
      transmission and their pharmacological diversity, their effects on primary
      glutamatergic afferents projecting to TCN represent a potential target for drug
      therapy of migraines and other types of orofacial pain.

PMID- 24667983
TI  - Quality assurance in quality of life assessment--measuring the validity of the
      King's Health Questionnaire.
AB  - INTRODUCTION AND HYPOTHESIS: The King's Health Questionnaire (KHQ) is a disease
      specific, self-administered questionnaire designed to assess the impact of
      urinary incontinence on quality of life (QOL) in women. To our knowledge there
      are no data on women's perception of completing the KHQ. Do they feel the KHQ to
      be useful and valuable or do they feel it to be too burdensome to be used in
      clinical practice? Therefore, we designed this study to evaluate patients'
      perception of the KHQ using QQ-10. The QQ-10 is a validated tool designed to
      measure patient's views on questionnaires. METHODS: This was a prospective
      observational study conducted at a tertiary referral teaching hospital. Patients
      were recruited from a one-stop urodynamics clinic. The study participants were
      asked to complete QQ-10 to give their views regarding KHQ. This produces two
      responses: positive value (communication, relevance, ease of use,
      comprehensiveness, enjoyableness, willingness to repeat) and negative burden
      (over-long, embarrassing, complicated, and upsetting). Mean scores and standard
      deviation for positive and negative responses were calculated RESULTS: The KHQ
      was found to have a high mean value (73; range 13-100) and a low mean burden (25;
      range 0-81) regarding responses to individual QQ-10 items. This was reinforced by
      the positive comments provided in the text boxes. CONCLUSIONS: Women perceived
      the KHQ as a valuable tool in their assessment without being bothersome.

PMID- 24667984
TI  - Inhibition of nerve growth factor-induced neurite outgrowth from PC12 cells by
      dexamethasone: signaling pathways through the glucocorticoid receptor and
      phosphorylated Akt and ERK1/2.
AB  - Glucocorticoids are important mediators of the stress response and are commonly
      employed as drugs for the suppression of immune rejection after organ
      transplantation. Previous investigations uncovered the possibility of mood
      depression in patients undergoing long-term treatment with synthetic
      glucocorticoids, including dexamethasone (DEX). Exogenous glucocorticoids and
      their synthetic derivatives can also adversely affect the development of the
      central nervous system. Although neurite extension from rat pheochromocytoma
      derived PC12 cells and a variety of primary neurons is stimulated by nerve growth
      factor (NGF), and signaling pathways triggered by the binding of NGF to tyrosine
      kinase receptor type 1 (TrkA) function in both neurite outgrowth and neuronal
      survival, the effect of DEX on the activation of regulatory proteins and pathways
      downstream of TrkA has not been well characterized. To analyze the influence of
      DEX on NGF-induced neurite outgrowth and signaling, PC12 cells, a widely utilized
      model of neuronal differentiation, were pretreated with the glucocorticoid prior
      to NGF induction. NGF-induced neurite outgrowth was attenuated by pretreatment
      with DEX, even in the absence of DEX after the addition of NGF. Moreover, DEX
      suppressed the phosphorylation of Akt and extracellular-regulated kinase 1/2
      (ERK1/2) in the neurite outgrowth signaling cascade initiated by NGF. Finally,
      the glucocorticoid receptor (GR) antagonist, RU38486, counteracted the inhibitory
      effect of DEX pretreatment, not only on the phosphorylation of Akt and ERK1/2,
      but also on neurite extension from PC12 cells. These results suggest that DEX
      binding to the GR impairs NGF-promoted neurite outgrowth by interfering with the
      activation/phosphorylation of Akt and ERK1/2. These novel findings are likely to
      be useful for elucidating the central nervous system depressive mechanism(s) of
      action of DEX and other glucocorticoids. 

PMID- 24667985
TI  - Targeting inhibitors of the tumor suppressor PP2A for the treatment of pancreatic
      cancer.
AB  - Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced
      stages when few effective therapies are available. Given the aggressive clinical
      course of this disease and lack of good treatment options, the development of new
      therapeutic agents for the treatment of pancreatic cancer is of the upmost
      importance. Several pathways that have shown to contribute to pancreatic cancer
      progression are negatively regulated by the tumor suppressor protein phosphatase
      2A (PP2A). Here, the endogenous inhibitors of PP2A, SET (also known as I2PP2A)
      and cancerous inhibitor of PP2A (CIP2A), were shown to be overexpressed in human
      pancreatic cancer, contributing to decreased PP2A activity and overexpression and
      stabilization of the oncoprotein c-Myc, a key PP2A target. Knockdown of SET or
      CIP2A increases PP2A activity, increases c-Myc degradation, and decreases the
      tumorigenic potential of pancreatic cancer cell lines both in vitro and in vivo.
      Moreover, treatment with a novel SET inhibitor, OP449, pharmacologically
      recapitulates the phenotypes and significantly reduces proliferation and
      tumorigenic potential of several pancreatic cancer cell lines, with an
      accompanying attenuation of cell growth and survival signaling. Furthermore,
      primary cells from patients with pancreatic cancer were sensitive to OP449
      treatment, indicating that PP2A-regulated pathways are highly relevant to this
      deadly disease. IMPLICATIONS: The PP2A inhibitors SET and CIP2A are overexpressed
      in human pancreatic cancer and are important for pancreatic cancer cell growth
      and transformation; thus, antagonizing SET and/or CIP2A may be an innovative
      approach for the treatment of human pancreatic cancer.

PMID- 24667987
TI  - Solvatochromic probes for detecting hydrogen-bond-donating solvents.
AB  - Hydrogen bonding heavily influences conformations, rate of reactions, and
      chemical equilibria. The development of a method to monitor hydrogen bonding
      interactions independent of polarity is challenging as both are linked. We have
      developed two solvatochromic dyes that detect hydrogen-bond-donating solvents.
      The unique solvatochromism of the triazine architecture has allowed the
      development of probes that monitor hydrogen-bond-donating species including
      water. 

PMID- 24667988
TI  - Indications for Caesarean sections in a rural hospital in the Highlands of Papua
      New Guinea.
AB  - We retrospectively documented indications for Caesarean sections in a rural
      district level hospital in the highlands of Papua New Guinea. Over a 53-month
      study period, 745 Caesarean sections were performed. Prolonged labour, previous
      history of Caesarean section, cephalopelvic disproportion, malpresentation and
      fetal distress accounted for over 88% of Caesarean sections performed. In older
      mothers (aged >30 years), antepartum haemorrhage (Fisher exact test, P = 0.05)
      and multiple indications (P = 0.001) were leading reasons for Caesarean sections
      while cephalopelvic disproportion (P = 0.005) was the leading indication in
      younger mothers. Further prospective studies incorporating perinatal and maternal
      mortality rates are required to optimise the value of Caesarean sections at
      district level hospitals in Papua New Guinea. 

PMID- 24667986
TI  - Novel insight into mutational landscape of head and neck squamous cell carcinoma.
AB  - Development of head and neck squamous cell carcinoma (HNSCC) is characterized by
      accumulation of mutations in several oncogenes and tumor suppressor genes. We
      have formerly described the mutation pattern of HNSCC and described NOTCH
      signaling pathway alterations. Given the complexity of the HNSCC, here we extend
      the previous study to understand the overall HNSCC mutation context and to
      discover additional genetic alterations. We performed high depth targeted exon
      sequencing of 51 highly actionable cancer-related genes with a high frequency of
      mutation across many cancer types, including head and neck. DNA from primary
      tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We
      identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected
      genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients.
      Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was
      mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients
      harbored 4-fold more TP53 mutations than HPV positive patients. These data
      confirm prior reports of the HNSCC mutational profile. Additionally, we detected
      mutations in two new genes, CEBPA and FES, which have not been previously
      reported in HNSCC. These data extend the spectrum of HNSCC mutations and define
      novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC
      without HPV infection. 

PMID- 24667989
TI  - Use of self-retaining barbed suture for rectal wall closure in transanal
      endoscopic microsurgery.
AB  - BACKGROUND: The aim of this study was to investigate the safety and efficacy of
      self-retaining barbed sutures in comparison with monofilament clip-fixated
      sutures for rectal wall closure in transanal endoscopic microsurgery. METHODS:
      Horizontal full-thickness wall defects (3.5 cm) of cattle rectal specimens were
      closed via transanal endoscopic microsurgery using a monofilament suture with
      clips at the end (Surgipro((r)) 2/0; Covidien, Mansfield, MA, USA, n = 25) or a
      self-retaining barbed suture (V-LocTM 180 3/0; Covidien, Mansfield, MA, USA, n =
      25). The primary endpoint was the pneumatic leakage pressure of the suture line.
      As a secondary endpoint, suture time was evaluated. RESULTS: The median pneumatic
      leakage pressure for barbed sutures was 45.5 mbar (range 17-106 mbar) and 33.5
      mbar (range 19-106 mbar) for monofilament sutures (p = 0.58). A pneumatic leak at
      a critical pressure below 25 mbar occurred in 3 cases with barbed sutures and in
      7 cases with monofilament sutures (p = 0.29). Median suturing time [19:25 min:s
      (range 12:00-33:30) vs. 20:41 (17:00-28:33), p = 0.23] did not differ between the
      two groups. CONCLUSIONS: Barbed sutures display the same bursting pressure as
      monofilament sutures and their use for rectal wall closure seems feasible.

PMID- 24667990
TI  - Endocrine crosstalk between muscle and bone.
AB  - The musculoskeletal system is a complex organ comprised of the skeletal bones,
      skeletal muscles, tendons, ligaments, cartilage, joints, and other connective
      tissue that physically and mechanically interact to provide animals and humans
      with the essential ability of locomotion. This mechanical interaction is
      undoubtedly essential for much of the diverse shape and forms observed in
      vertebrates and even in invertebrates with rudimentary musculoskeletal systems
      such as fish. It makes sense from a historical point of view that the mechanical
      theories of musculoskeletal development have had tremendous influence of our
      understanding of biology, because these relationships are clear and palpable.
      Less visible to the naked eye or even to the microscope is the biochemical
      interaction among the individual players of the musculoskeletal system. It was
      only in recent years that we have begun to appreciate that beyond this mechanical
      coupling of muscle and bones, these 2 tissues function at a higher level through
      crosstalk signaling mechanisms that are important for the function of the
      concomitant tissue. Our brief review attempts to present some of the key concepts
      of these new concepts and is outline to present muscles and bones as
      secretory/endocrine organs, the evidence for mutual genetic and tissue
      interactions, pathophysiological examples of crosstalk, and the exciting new
      directions for this promising field of research aimed at understanding the
      biochemical/molecular coupling of these 2 intimately associated tissues. 

PMID- 24667991
TI  - Paraneoplastic overlap syndrome in non-small squamous cell lung carcinoma.
AB  - This is a case of paraneoplastic overlap of limbic encephalitis and opsoclonus
      myoclonus in a patient with non-small squamous cell lung carcinoma. 

PMID- 24667992
TI  - Brassinosteroid-mediated regulation of agronomic traits in rice.
AB  - Brassinosteroids (BRs) are a group of steroid phytohormones with wide-ranging
      biological activity. Genetic, genomic and proteomic studies have greatly advanced
      our understanding of BR signaling in Arabidopsis and revealed a connected signal
      transduction pathway from the cell surface receptor kinase BRASSINOSTEROID
      INSENSITIVE1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) to the
      BRASSINAZOLE-RESISTANT1 (BZR1) family of transcription factors and their targets
      mediating physiological functions. However, compared with the dicot model plant
      Arabidopsis, much less is known about BR signaling in rice, which is a monocot.
      In this review, we provide an update on the progress made by BR studies in rice
      and discuss how BR regulates various important agronomic traits to determine rice
      grain yield. Specifically, we discuss the function of novel components including
      LEAF AND TILLER ANGLE INCREASED CONTROLLER (LIC), DWARF and LOW-TILLERING (DLT),
      DWARF1 (D1) and TAIHU DWARF1 (TUD1) in rice BR signaling, and provide a rice BR
      signaling pathway model that involves a BRI1-dependent pathway as well as a G
      protein alpha subunit-mediated signaling pathway. The recent significant advances
      in our understanding of BR-mediated molecular mechanisms underlying agronomic
      traits will be of great help for rice molecular breeding.

PMID- 24667993
TI  - The Arabidopsis kinesin gene AtKin-1 plays a role in the nuclear division process
      during megagametogenesis.
AB  - KEY MESSAGE: Atkin - 1 , the only Kinesin-1 member of Arabidopsis thaliana ,
      plays a role during female gametogenesis through regulation of nuclear division
      cycles. Kinesins are microtubule-dependent motor proteins found in eukaryotic
      organisms. They constitute a superfamily that can be further classified into at
      least 14 families. In the Kinesin-1 family, members from animal and fungi play
      roles in long-distance transport of organelles and vesicles. Although Kinesin-1
      like sequences have been identified in higher plants, little is known about their
      function in plant cells, other than in a recently identified Kinesin-1-like
      protein in a rice pollen semi-sterile mutant. In this study, the gene encoding
      the only Kinesin-1 member in Arabidopsis, AtKin-1 was found to be specifically
      expressed in ovules and anthers. AtKin-1 loss-of-function mutants showed
      substantially aborted ovules in siliques, and this finding was supported by
      complementation testing. Reciprocal crossing between mutant and wild-type plants
      indicated that a defect in AtKin-1 results in partially aborted megagametophytes,
      with no observable effects on pollen fertility. Further observation of ovule
      development in the mutant pistils indicated that the enlargement of the megaspore
      was blocked and nuclear division arrested at the one-nucleate stage during embryo
      sac formation. Our data suggest that AtKin-1 plays a role in the nuclear division
      cycles during megagametogenesis.

PMID- 24667994
TI  - Bimatoprost 0.03%/timolol 0.5% preservative-free ophthalmic solution versus
      bimatoprost 0.03%/timolol 0.5% ophthalmic solution (Ganfort) for glaucoma or
      ocular hypertension: a 12-week randomised controlled trial.
AB  - AIM: To compare the efficacy and safety of single-dose bimatoprost 0.03%/timolol
      0.5% preservative-free (PF) ophthalmic solution with bimatoprost 0.03%/timolol
      0.5% ophthalmic solution in patients with open-angle glaucoma or ocular
      hypertension. METHODS: In this multicentre, randomised, parallel-group study,
      patients were randomised to bimatoprost/timolol PF or bimatoprost/timolol once
      daily in the morning for 12 weeks. Primary efficacy endpoints, reflecting
      differing regional regulatory requirements, included change from baseline in
      worse eye intraocular pressure (IOP) in the per-protocol population at week 12,
      and the average eye IOP at weeks 2, 6 and 12 in the intent-to-treat population.
      RESULTS: 561 patients were randomised (278 to bimatoprost/timolol PF; 283 to
      bimatoprost/timolol); 96.3% completed the study. Both treatment groups showed
      statistically and clinically significant mean decreases from baseline in worse
      eye IOP and in average eye IOP at all follow-up time points (p<0.001).
      Bimatoprost/timolol PF met all pre-established criteria for non-inferiority and
      equivalence to bimatoprost/timolol. Ocular adverse events were similar between
      treatment groups, with conjunctival hyperaemia being the most frequent. Most were
      mild or moderate in severity. CONCLUSIONS: Bimatoprost/timolol PF demonstrated
      non-inferiority and equivalence in IOP lowering compared with
      bimatoprost/timolol, with no significant differences in safety and tolerability.
      TRIAL REGISTRATION NUMBER: NCT01177098.

PMID- 24667996
TI  - A density functional theory study of catalytic sites for oxygen reduction in
      Fe/N/C catalysts used in H2/O2 fuel cells.
AB  - The oxygen reduction catalytic activity of carbon-supported FeN4 moieties
      bridging micropores between two graphene sheets was investigated by density
      functional theory (DFT). Based on the FeN(2+2)/C structure proposed earlier by
      our group, two types of FeN(2+2)/C structures were considered: one mostly planar
      and one in which the Fe ion is significantly displaced out of the graphitic
      plane. A structure in which the FeN4 moiety is embedded in an extended graphene
      sheet (FeN/C) was also considered. In addition, we have investigated the
      influence of an axial pyridine group approaching the Fe centre. The formation
      energy is lowest for the planar FeN(2+2)/C structure. The overall downhill
      behaviour of the relative free energy vs. the reaction step suggests that most
      structures have catalytic activity near zero potential. This conclusion is
      further supported by calculations of the binding energies of adsorbed O2 and H2O
      and of the O-O bond lengths of adsorbed O2 and OOH. The side-on interaction of
      adsorbed O2 is preferred over the end-on interaction for the three basic
      structures without the axial pyridine. The pyridine coordination produces a
      stronger binding of O2 for the planar FeN(2+2)/C and the FeN/C structures as well
      as a dominant end-on interaction of O2. The energy levels of the planar
      FeN(2+2)/C structure with and without the pyridine ligand are nearly equal for
      iron spin states S = 1 and S = 2, suggesting that both configurations are formed
      with similar concentration during the preparation process, as also previously
      found for two of the iron sites by Mossbauer spectroscopy experiments.

PMID- 24667995
TI  - Discriminating cellular heterogeneity using microwell-based RNA cytometry.
AB  - Discriminating cellular heterogeneity is important for understanding cellular
      physiology. However, it is limited by the technical difficulties of single-cell
      measurements. Here we develop a two-stage system to determine cellular
      heterogeneity. In the first stage, we perform multiplex single-cell RNA cytometry
      in a microwell array containing over 60,000 reaction chambers. In the second
      stage, we use the RNA cytometry data to determine cellular heterogeneity by
      providing a heterogeneity likelihood score (HLS). Moreover, we use Monte-Carlo
      simulation and RNA cytometry data to calculate the minimum number of cells
      required for detecting heterogeneity. We apply this system to characterize the
      RNA distributions of ageing-related genes in a highly purified mouse
      haematopoietic stem cell population. We identify genes that reveal novel
      heterogeneity of these cells. We also show that changes in expression of genes
      such as Birc6 during ageing can be attributed to the shift of relative portions
      of cells in the high-expressing subgroup versus low-expressing subgroup. 

PMID- 24667997
TI  - Establishment of a stable aryl hydrocarbon receptor-responsive HepG2 cell line.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor.
      It heterodimerizes with aryl hydrocarbon nuclear translocator, binds to the
      xenobiotic-responsive element (XRE), and enhances the transcription of genes
      encoding xenobiotic metabolizing enzymes. AHR also plays important roles in the
      inhibition of intestinal carcinogenesis and the modulation of gut immunity. It is
      very important to screen for AHR-activating compounds because those are expected
      to produce the AHR-mediated physiological functions. Until now, AHR-mediated
      transcriptional activity represented by the transcriptional activity of CYP1A1 in
      luciferase assay has been applied as a screening procedure for AHR-activating
      compounds. However, the AHR-mediated transcriptional activity did not necessarily
      correspond with the CYP1A1 transcriptional activity. To evaluate AHR-mediated
      transcriptional activity more specifically, and to screen for AHR-activating
      compounds, we establish a stable AHR-responsive HepG2 cell line by co
      transfection of an AHR expression vector and an AHR-responsive vector (pGL3-XRE)
      containing a luciferase gene and three tandemly arranged XRE elements into a
      human hepatoma derived cell line, HepG2. The induction of luciferase activity in
      the stable AHR-responsive HepG2 cell line by typical AHR activators occurred in
      time- and concentration-dependent manners. By assessing the AHR target genes
      CYP1A1, UGT1A1, and ABCG2, an AHR activator-mediated induction was observed at
      mRNA level. Furthermore, the AHR activator-mediated induction of luciferase
      activity was positively correlated with the mRNA levels of CYP1A1, UGT1A1, and
      ABCG2. These findings verified the usefulness of the established stable AHR
      responsive HepG2 cell line for the screening of AHR-activating compounds. 

PMID- 24667999
TI  - Insight into the amplification by methylated urea of the anion specificity of
      macromolecules.
AB  - Methylated urea and sugar are chaotropic and kosmotropic osmolytes, respectively.
      In the present work, we have investigated the specific anion effect on the lower
      critical solution temperature (LCST) behavior of poly(N-isopropylacrylamide)
      (PNIPAM) in the presence of methylated urea or sugars. Differential scanning
      calorimetry studies revealed that tetramethylurea can adsorb onto the PNIPAM
      surface, but glucose is excluded from the PNIPAM surface. The specific anion
      effect on the LCST behavior of PNIPAM is amplified by methylated urea but not by
      sugars. The amplification of the anion specificity by methylated urea is
      attributed to an increased difference in the anion-specific polarization of
      hydrogen bonds, induced by the formation of PNIPAM/methylated urea complexes via
      hydrophobic interactions. As the number of methyl groups on the methylated urea
      increases, the extent of amplification of the anion specificity increases due to
      increasing hydrophobic interactions between the PNIPAM and methylated urea.
      Additionally, no amplification of the anion specificity is observed in the
      presence of urea because a PNIPAM/urea complex cannot be formed via hydrophobic
      interactions. 

PMID- 24668000
TI  - Photocatalytic chemoselective reduction of epoxides to alkenes along with
      formation of ketones in alcoholic suspensions of silver-loaded titanium(iv) oxide
      at room temperature without the use of reducing gases.
AB  - (2,3-Epoxypropyl)benzene was chemoselectively reduced to allylbenzene along with
      formation of ketones in alcoholic suspensions of a silver-loaded titanium(iv)
      oxide photocatalyst at room temperature under atmospheric pressure without the
      use of reducing gases, and various epoxides were also reduced to the
      corresponding alkenes. 

PMID- 24667998
TI  - Verbal fluency in focal epilepsy: a systematic review and meta-analysis.
AB  - Testing of verbal fluency is currently part of standard presurgical
      neuropsychological assessment for patients with focal epilepsy. However, to date
      no systematic review has been conducted on semantic (SVF) and phonemic verbal
      fluency (PVF) in this patient group. The present review compares verbal fluency
      between healthy control subjects and subgroups of adult presurgical patients with
      focal epilepsy according to lateralisation and localisation of the dysfunction.
      PubMed was searched with a comprehensive search string. Abstracts of all studies
      and full-texts of potentially relevant studies were screened. Study quality was
      assessed by independent raters according to predefined criteria. 39 studies were
      included. Meta-analyses were performed to compare SVF and PVF across groups of
      patients with temporal (TLE) and frontal lobe epilepsy (FLE) as well as healthy
      controls (HC). Both patients with left- and right sided TLE were impaired on SVF
      and PVF compared to HC. Patients with left-sided TLE were slightly more impaired
      than patients with right-sided TLE. Patients with FLE showed a larger impairment
      in PVF than patients with TLE, whereas on SVF there was no difference between FLE
      and TLE. For TLE comparisons the study pool seems to have been sufficient,
      whereas more studies are needed to verify results for FLE. Semantic verbal
      fluency might not differentiate between FLE and TLE. While verbal fluency
      impairment was anticipated, especially in left-sided TLE and FLE patients, the
      impairment in patients with right-sided TLE was larger than expected. Results are
      discussed with regard to neuropsychological theory and practice. 

PMID- 24668001
TI  - The pharmacokinetics and pharmacodynamics of TOL101, a murine IgM anti-human
      alphabeta T cell receptor antibody, in renal transplant patients.
AB  - BACKGROUND AND OBJECTIVES: TOL101 is a highly selective murine anti-alphabeta T
      cell receptor (TCR) IgM antibody and has recently completed phase II testing in
      primary renal transplant patients. This study was undertaken to determine the
      pharmacokinetic, pharmacodynamic, and immunogenic profile of TOL101. METHODS:
      Nine cohorts of two to six patients received at least five daily doses (of, or
      combination of, 0.28, 1.4, 7, 14, 28, or 42 mg) of TOL-101 administered at
      successively higher doses. Semi-logarithmic graphs of serum TOL101 concentration
      versus time supported the use of a one-compartment intravenous infusion
      pharmacokinetic model. The model was parameterized in terms of serum clearance
      (CL) and volume of distribution (V d). RESULTS: There was a trend toward a
      decrease in serum CL as the dose increased from 1.4 to 28 mg. However, the mean
      values for CL and V d were consistent across the cohorts that received 28, 32,
      and 42 mg. The mean +/- standard deviation half-lives for these five cohorts
      ranged from 15.1 +/- 7.35 to 28.6 +/- 8.46 h, with an overall mean of 23.8 h,
      supporting both daily as well as fixed (i.e., not based on weight) dosing. Using
      CD3+ <=25 cells/mm(3) as the primary pharmacodynamic marker, all non-responders
      were in the 0.28, 1.4, or 7 mg cohorts, suggesting that starting doses above 14
      mg are required. Finally, one patient out of 36 was found to have anti-drug
      antibody. CONCLUSIONS: Together, the data show that while TOL101 is a highly
      potent anti-TCR antibody, its pharmacological profile is somewhat versatile,
      allowing for daily dosing without immunogenicity concerns.

PMID- 24668002
TI  - The role of water co-adsorption on the modification of ZnO nanowires using acetic
      acid.
AB  - Density functional theory (DFT) and Car-Parinello molecular dynamic simulations
      were employed to investigate the interaction of acetic acid with non-polar facets
      of ultra-thin ZnO nanowires. We consider both a dry and a water environment as
      well as different molecule coverages for the hydrated system. Our calculations
      reveal that the fully-covered nanowire is energetically favored in the aqueous
      environment at room temperature. We also identified a minor influence of liquid
      water on the denticity of the ligands for the fully modified system. However, a
      monodentate adsorption is expected for a half-covered nanowire due to strong
      ligand-water interactions. 

PMID- 24668004
TI  - How long should we treat?
AB  - Osteoporosis is a chronic disease, for which effective drugs are available. These
      drugs have reduced the risk of osteoporosis-related fractures in robust trials of
      3-5 years duration. There is no evidence of anti-fracture efficacy for treatments
      of longer duration. The consequences of stopping treatments are very different
      for the different molecules. Bisphosphonates can be safely discontinued after 3-5
      years of treatment if there was optimal adherence and if patients are no longer
      osteoporotic. This discontinuation cannot be applied in patients with recent
      fractures or for other treatments. Safety of prolonged treatment is a huge
      concern which must be managed appropriately. The decision of a prolonged
      treatment is driven by the underlying risk of fracture. This risk must be
      assessed regularly in order to share with the patient the benefit-risk ratio of
      prolonged treatment.

PMID- 24668005
TI  - Validation of a short questionnaire for estimating dietary calcium intakes.
AB  - Concern about calcium supplements, and mainly minor side effects (e.g.
      constipation) impacting on compliance, means that assessing dietary calcium
      intake is important. There is no suitable biomarker. Compared to food diaries, a
      short questionnaire was an efficient way of confirming that patients had adequate
      calcium intakes (>700 or >1,000 mg) INTRODUCTION: Calcium is usually given
      alongside treatments for osteoporosis, but recent concerns about potential side
      effects have led to questioning whether supplements are always necessary. It is
      difficult to assess calcium intake in a clinical setting and be certain that the
      patient is getting enough calcium. The aim of this study was to determine whether
      a short questionnaire for estimating dietary calcium intakes in a clinical
      setting was fit for purpose. METHODS: We assessed dietary calcium intakes using a
      short questionnaire (CaQ) in patients attending an osteoporosis clinic (n = 117)
      and compared them with calcium intakes obtained from a 7-day food diary (n = 72)
      and a food frequency questionnaire (FFQ) (n = 33). RESULTS: Mean (SD) daily
      calcium intakes from the CaQ were 836 (348) mg; from the diaries, 949 (384) mg;
      and from the FFQ, 1,141 (387) mg. The positive predictive value (PPV) was >80%
      for calcium cut-offs > 700 mg and 70% for cut-offs > 1,000 mg. The calcium
      intakes for the false positives results were not far below the cut-off. For 1,200
      mg, the PPV was 67% or less. CONCLUSION: The CaQ is an adequate tool for
      assessing whether a patient has daily calcium intakes above 700 or 1,000 mg; if
      below these cut-offs, it is possible that the patient still has enough calcium in
      the diet, which could be clarified by questioning the patient further. As there
      were few patients with calcium intakes above 1,200 mg a day, the CaQ cannot be
      recommended as a tool for confirming higher dietary calcium intakes.

PMID- 24668006
TI  - Higher serum uric acid as a protective factor against incident osteoporotic
      fractures in Korean men: a longitudinal study using the National Claim Registry.
AB  - In this large longitudinal study of 16,078 Korean men aged 50 years or older, we
      observed that baseline elevation of serum uric acid level significantly
      associated with a lower risk of incident fractures at osteoporosis-related sites
      during an average follow-up period of 3 years. INTRODUCTION: Male osteoporosis
      and related fractures are becoming recognized as important public health
      concerns. Oxidative stress has detrimental effects on bone metabolism, and serum
      uric acid (UA) is known to be a strong endogenous antioxidant. In the present
      study, we performed a large longitudinal study with an average follow-up period
      of 3 years to clarify the role of UA on the risk of incident osteoporotic
      fractures (OFs). METHODS: A total of 16,078 Korean men aged 50 years or older who
      had undergone comprehensive routine health examinations were enrolled. Incident
      fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and
      proximal humerus) that occurred after the baseline examinations were identified
      from the nationwide claims database of the Health Insurance Review and Assessment
      Service of Korea by using selected International Classification of Diseases, 10th
      revision codes. RESULTS: In total, 158 (1.0 %) men developed incident OFs. The
      event rate was 33.1 per 10,000 person-years. Subjects without incident OFs had
      6.0 % higher serum UA levels than subjects with OFs (P = 0.001). Multivariable
      adjusted Cox proportional hazard analyses adjusted for age, body mass index,
      glomerular filtration rate, lifestyle factors, medical and drug histories, and
      the presence of baseline radiological vertebral fractures revealed that the
      hazard ratio per standard deviation increase of baseline UA levels for the
      development of incident OFs was 0.829 (95 % CI = 0.695-0.989, P = 0.038).
      CONCLUSIONS: These data provide the epidemiological evidence that serum UA may
      act as a protective factor against the development of incident OFs in Korean men.

PMID- 24668007
TI  - Bio-inspired synthesis of rare and unnatural carbohydrates and cyclitols through
      strain driven epimerization.
AB  - We report a bio-inspired, strain driven epimerization of trans-ketals to cis
      ketals through an enolate intermediate. Swern oxidation of a hydroxyl group
      adjacent to a trans-ketal effects both oxidation and its epimerization to cis
      ketal. This novel and general strategy allows inversion of up to three contiguous
      stereocenters and has been illustrated by the synthesis of several unnatural/rare
      isomers of carbohydrates/cyclitols from their naturally abundant isomers. 

PMID- 24668008
TI  - Quantitative sodium MR imaging of native versus transplanted kidneys using a dual
      tuned proton/sodium (1H/ 23Na) coil: initial experience.
AB  - OBJECTIVES: To compare sodium ((23)Na) characteristics between native and
      transplanted kidneys using dual-tuned proton ((1)H)/sodium MRI. METHODS: Six
      healthy volunteers and six renal transplant patients (3 normal function, 3 acute
      allograft rejection) were included. Proton/sodium MRI was obtained at 3 T using a
      dual-tuned coil. Signal to noise ratio (SNR), sodium concentration ([(23)Na]) and
      cortico-medullary sodium gradient (CMSG) were measured. Reproducibility of
      [(23)Na] measurement was also tested. SNR, [(23)Na] and CMSG of the native and
      transplanted kidneys were compared. RESULTS: Proton and sodium images of kidneys
      were successfully acquired. SNR and [(23)Na] measurements of the native kidneys
      were reproducible at two different sessions. [(23)Na] and CMSG of the
      transplanted kidneys was significantly lower than those of the native kidneys:
      153.5 +/- 11.9 vs. 192.9 +/- 9.6 mM (P = 0.002) and 8.9 +/- 1.5 vs. 10.5 +/- 0.9
      mM/mm (P = 0.041), respectively. [(23)Na] and CMSG of the transplanted kidneys
      with normal function vs. acute rejection were not statistically different.
      CONCLUSIONS: Sodium quantification of kidneys was reliably performed using
      proton/sodium MRI. [(23)Na] and CMSG of the transplanted kidneys were lower than
      those of the native kidneys, but without a statistically significant difference
      between patients with or without renal allograft rejection. KEY POINTS: Dual
      tuned proton/sodium RF coil enables co-registered proton and sodium MRI.
      Structural and sodium biochemical property can be acquired by dual-tuned
      proton/sodium MRI. Sodium and sodium gradient of kidneys can be measured by dual
      tuned MRI. Sodium concentration was lower in transplanted kidneys than in native
      kidneys. Sodium gradient of transplanted kidneys was lower than for native
      kidneys.

PMID- 24668009
TI  - MR diffusion imaging for preoperative staging of myometrial invasion in patients
      with endometrial cancer: a systematic review and meta-analysis.
AB  - OBJECTIVES: To compare the diagnostic accuracy of dynamic contrast-enhanced (DCE)
      and diffusion-weighted (DW) MR imaging in detecting deep myometrial invasion in
      endometrial cancer, using surgical-pathological staging as reference standard.
      METHODS: After searching a wide range of electronic databases and screening
      titles/abstracts, we obtained full papers for potentially eligible studies and
      evaluated according to predefined inclusion criteria. Quality assessment was
      conducted by adapting the Quality Assessment of Diagnostic Accuracy Studies-2
      (QUADAS-2) checklist. From each study, we extracted information on diagnostic
      performance of DW and DCE sequences. After exploring heterogeneity, we adopted a
      bivariate generalized linear mixed model to compare the effect of the two MR
      sequences jointly on sensitivity and specificity. RESULTS: Nine studies (442
      patients) were considered. Significant evidence of heterogeneity was found only
      for specificity, both in DW and DCE imaging (I (2)  = 70.8 % and 70.6 %). Pooled
      sensitivity of DW and DCE was 0.86 and specificity did not significantly differ
      (p = 0.16) between the two sequences (DW = 0.86 and DCE = 0.82). No difference
      was found between 3-T and 1.5-T MR. There was no evidence of publication bias.
      CONCLUSIONS: MR diagnostic accuracy in presurgical detection of deep myometrial
      infiltration in endometrial cancer is high. DCE and DW imaging do not differ in
      sensitivity and specificity. KEY POINTS: Myometrial invasion is the most
      important morphological prognostic feature of endometrial cancer. MR diagnostic
      accuracy in presurgical detection of deep myometrial infiltration is high. MR
      examination including T2 and DCE imaging is considered the reference standard. DW
      imaging has been increasingly employed with heterogeneous results. This meta
      analysis shows that DCE and DW do not differ in diagnostic accuracy.

PMID- 24668010
TI  - Contrast agent bolus tracking with a fixed threshold or a manual fast start for
      coronary CT angiography.
AB  - OBJECTIVES: Comparison of bolus tracking with a fixed threshold versus a manual
      fast start for coronary CT angiography. METHODS: We retrospectively analysed 320
      row coronary CT angiography of 50 patients with suspected or known coronary
      artery disease. Twenty-five examinations were initiated by a bolus tracking
      method (group 1), 25 examinations with a manual fast surestart (group 2).
      RESULTS: Mean attenuation values in the ascending aorta were 519 +/- 111
      Hounsfield units (HU) in group 1 and 476 +/- 65 HU in group 2 (p = 0.10).
      Assessable vessel lengths were 171 +/- 44 mm vs 172 +/- 29 mm for the right
      coronary artery (p = 0.91), 11 +/- 4 mm vs 12 +/- 4 mm for the left main (p =
      0.9), 163 +/- 28 mm vs 151 +/- 26 mm for the left anterior descending coronary
      artery (p = 0.11) and 125 +/- 41 mm vs 110 +/- 37 mm for the left circumflex
      coronary artery (p = 0.18). Image quality for all coronary arteries was not
      significantly different between the groups (p > 0.41). The attenuation ratio
      between the left and right ventricle was 2.8 +/- 0.7 vs 3.6 +/- 1.0 (p = 0.003).
      Significantly less contrast agent was used in group 2 (64 +/- 6 ml vs 80 +/- 0
      ml; p < 0.001). CONCLUSIONS: Bolus tracking with a fixed threshold and with a
      manual fast start are both suitable methods; the fast start allowed a reduction
      of contrast agent volumes. KEY POINTS: Fixed threshold bolus tracking is suitable
      for coronary 320-row CT angiography. Manual fast start bolus tracking can reduce
      contrast agent volumes. Manual fast start and fixed threshold initiation achieve
      good image quality. Fixed threshold bolus tracking achieves a more reliable
      contrast bolus position.

PMID- 24668012
TI  - Aqueous solvation of HgClOH. Stepwise DFT solvation and Born-Oppenheimer
      molecular dynamics studies of the HgClOH-(H2O)24 complex.
AB  - We address the aqueous solvation of HgClOH through a systematic study of stepwise
      hydration considering the HgClOH-(H2O)n structures with n = 1-24. After
      calibration of the DFT method, the electronic calculations have been carried out
      using the B3PW91 exchange-correlation functional. For n < 5 the main geometrical
      parameters and incremental binding energies are in agreement with counterpoise
      corrected MP2/AVTZ static values and BO-MP2 dynamic averages. For n > 15 three
      direct water-Hg interactions appear during the hydration process and a
      pentacoordinated trigonal bipyramid apical pattern around Hg is found. 22 water
      molecules are needed to build the first solvation shell. Unlike microsolvated
      HgCl2, no stable equatorial trigonal bipyramid was found. Optimizations with the
      Polarizable Continuum Model lead to structures with extremely large Hg-O(water)
      distances because of a dominant solvation effect on the explicit water molecules;
      however, this overestimation diminishes for large values of n. A DFT Born
      Oppenheimer molecular dynamics simulation at T = 700 K revealed the stability of
      the HgClOH-(H2O)24 complex with an average trigonal bipyramid Hg-coordination
      pattern, in accordance with the static cluster description. After thermalization
      is achieved, the exchange rate of the Hg-coordinated water molecules is estimated
      to be ca. 10(11) s(-1). 

PMID- 24668011
TI  - Therapy in ST-elevation myocardial infarction: reperfusion strategies,
      pharmacology and stent selection.
AB  - OPINION STATEMENT: The estimated annual incidence of new and recurrent myocardial
      infarction (MI) in the U.S. is 715,000 events. Primary percutaneous coronary
      intervention (PCI) is the reperfusion strategy of choice in most patients with
      acute ST-elevation myocardial infarction (STEMI). Recent advances in percutaneous
      techniques and devices, including manual aspiration catheters and newer
      generation drug eluting stents and pharmacologic therapies, such as novel
      antiplatelets and anticoagulants have led to significant improvements in the
      acute and long-term outcomes for these patients. Implementation of community-wide
      systems directed to shorten treatment times tied to closely monitored quality
      improvement processes have led to further advances in STEMI care. Recent data
      suggests that transradial access for primary PCI is associated with improved
      outcomes. This contemporary review discusses the strategies for reperfusion,
      pharmacological therapy and stent selection process involved in STEMI.

PMID- 24668013
TI  - Species richness and trait composition of butterfly assemblages change along an
      altitudinal gradient.
AB  - Species richness patterns along altitudinal gradients are well-documented
      ecological phenomena, yet very little data are available on how environmental
      filtering processes influence the composition and traits of butterfly assemblages
      at high altitudes. We have studied the diversity patterns of butterfly species at
      34 sites along an altitudinal gradient ranging from 600 to 2,000 m a.s.l. in the
      National Park Berchtesgaden (Germany) and analysed traits of butterfly
      assemblages associated with dispersal capacity, reproductive strategies and
      developmental time from lowlands to highlands, including phylogenetic analyses.
      We found a linear decline in butterfly species richness along the altitudinal
      gradient, but the phylogenetic relatedness of the butterfly assemblages did not
      increase with altitude. Compared to butterfly assemblages at lower altitudes,
      those at higher altitudes were composed of species with larger wings (on average
      9%) which laid an average of 68% more eggs. In contrast, egg maturation time in
      butterfly assemblages decreased by about 22% along the altitudinal gradient.
      Further, butterfly assemblages at higher altitudes were increasingly dominated by
      less widespread species. Based on our abundance data, but not on data in the
      literature, population density increased with altitude, suggesting a reversed
      density-distribution relationship, with higher population densities of habitat
      specialists in harsh environments. In conclusion, our data provide evidence for
      significant shifts in the composition of butterfly assemblages and for the
      dominance of different traits along the altitudinal gradient. In our study, these
      changes were mainly driven by environmental factors, whereas phylogenetic
      filtering played a minor role along the studied altitudinal range.

PMID- 24668014
TI  - Nematode community shifts in response to experimental warming and canopy
      conditions are associated with plant community changes in the temperate-boreal
      forest ecotone.
AB  - Global climate warming is one of the key forces driving plant community shifts,
      such as range shifts of temperate species into boreal forests. As plant community
      shifts are slow to observe, ecotones, boundaries between two ecosystems, are
      target areas for providing early evidence of ecological responses to warming. The
      role of soil fauna is poorly explored in ecotones, although their positive and
      negative effects on plant species can influence plant community structure. We
      studied nematode communities in response to experimental warming (ambient, +1.7,
      +3.4  degrees C) in soils of closed and open canopy forest in the temperate
      boreal ecotone of Minnesota, USA and calculated various established nematode
      indices. We estimated species-specific coverage of understory herbaceous and
      shrub plant species from the same experimental plots and tested if changes in the
      nematode community are associated with plant cover and composition. Individual
      nematode trophic groups did not differ among warming treatments, but the ratio
      between microbial-feeding and plant-feeding nematodes increased significantly and
      consistently with warming in both closed and open canopy areas and at both
      experimental field sites. The increase in this ratio was positively correlated
      with total cover of understory plant species, perhaps due to increased predation
      pressure on soil microorganisms causing higher nutrient availability for plants.
      Multivariate analyses revealed that temperature treatment, canopy conditions and
      nematode density consistently shaped understory plant communities across
      experimental sites. Our findings suggest that warming-induced changes in nematode
      community structure are associated with shifts in plant community composition and
      productivity in the temperate-boreal forest ecotones. 

PMID- 24668015
TI  - Interactive effects of salinity and a predator on mosquito oviposition and larval
      performance.
AB  - Oviposition habitat selection (OHS) is increasingly being recognized as playing a
      large role in explaining mosquito distributions and community assemblages. Most
      studies have assessed the role of single factors affecting OHS, while in nature,
      oviposition patterns are most likely explained by multiple, interacting biotic
      and abiotic factors. Determining how various factors interact to affect OHS is
      important for understanding metapopulation and metacommunity dynamics. We
      investigated the individual and interactive effects of three water salinities (0,
      15 and 30 p.p.t. NaCl added) and the aquatic predator Anisops debilis Perplexa
      (Hemiptera: Notonectidae) on OHS and larval performance of the mosquitoes
      Ochlerotatus caspius Pallas and Culiseta longiareolata Macquart (Diptera:
      Culicidae) in outdoor-artificial-pool and laboratory experiments. C.
      longiareolata inhabited only freshwater pools, strongly avoided pools containing
      A. debilis, and larvae experienced lower survival in the presence of A. debilis.
      Salinity concentration interacted strongly with the predator in affecting OHS and
      larval survival of O. caspius; oviposition increased with increasing salinity in
      the absence of the predator and decreased with increasing salinity in the
      presence of the predator. O. caspius larval survival in predator-free pools was
      lowest in freshwater and highest at intermediate salinity. In predator pools,
      survival was highest at high salinity, where predation rate was shown to be
      lowest in the laboratory. Our results highlight that assessing the role of single
      factors in affecting mosquito distributions can be misleading. Instead, multiple
      factors may interact to affect oviposition patterns and larval performance. 

PMID- 24668016
TI  - Pyrosequencing of prey DNA in faeces of carnivorous land snails to facilitate
      ecological restoration and relocation programmes.
AB  - Identifying and understanding predator diets is of high importance in biological
      conservation. This is particularly true for the introduction, establishment and
      maintenance of predator populations in newly created or modified ecological
      communities, such as translocation sites or restored habitats. Conservation
      status of predators may not permit captive feeding trials or intrusive gut
      content methods, so non-intrusive diet assessment is required, such as faecal
      analysis. However, prey such as earthworms leave no morphological clues suitable
      for accurately discriminating between species consumed through visual faecal
      analysis. This study uses non-intrusive molecular methods on earthworm DNA
      extracted from the faeces of the carnivorous land snail Powelliphanta
      patrickensis to identify its earthworm diet and any seasonal trends. Data from
      454-pyrosequencing revealed earthworm DNA in all samples (n = 60). Sequences were
      compared to a DNA library created from published and unpublished studies of New
      Zealand's endemic earthworms and online databases. Unidentified earthworm
      sequences were clustered into molecular operational taxonomic units (MOTUs).
      Twenty-six MOTUs were identified, 17 of which matched the library, whereas nine
      did not. Similarity indices indicate that there were seasonal differences (P <
      0.05) in the earthworm communities represented in the summer and the winter
      diets. This study highlights the importance of utilising the vast body of data
      generated by pyrosequencing to investigate potential temporal diet shifts in
      protected species. The method described here is widely applicable to a wide range
      of predatory species of conservation interest and can further inform habitat
      restoration and relocation programmes to optimize the long-term survival of the
      target species.

PMID- 24668017
TI  - Short- and long-term effects of unpredictable repeated negative stimuli on
      Japanese quail's fear of humans.
AB  - Numerous aversive events occur in poultry production, and if repeated and
      unpredictable, can result in an impaired welfare. Some events such as handling
      can be perceived negatively and it is of interest to understand how humans'
      behaviour could affect poultry's behaviours and especially its avoidance of
      humans. Our aim was to evaluate short- and long-lasting effects of a 3-week
      procedure involving unpredictable repeated negative stimuli (URNS) applied during
      the post-juvenile period on quail's reactivity to humans. We compared the
      reactions of two sets of quail: URNS was applied to one set (treated quail) and
      the other set was left undisturbed (control quail). When two weeks old, treated
      quail were exposed to a variety of negative stimuli, either applied automatically
      or involving human presence. One and seven weeks after the termination of the
      procedure, the reactivity of control and treated quail to a passive human being
      was evaluated. Furthermore, the experimenter with her hand on a trough containing
      a mealworm assessed the propensity of quail of both groups to habituate to feed
      close to a human being. In the presence of a seated observer, treated quail were
      more inhibited and more alert than control quail. Likewise, seven weeks after the
      end of the URNS procedure, more treated than control quail adopted a fear
      posture. Moreover, whereas control quail spent as much time in the different
      areas of their cages, treated quail spent more time in the rear part of their
      cages. Finally, whereas control quail habituated gradually to feed near the
      experimenter's hand, treated quail did not. All these tests evidence negative
      short- and long-term effects on treated quail's reactivity to a passive human
      being and on their habituation to a human being when her presence is positively
      reinforced. This highlights the importance of young poultry's experience with
      humans in production. 

PMID- 24668018
TI  - Optimization of heterologous expression of the phytase (PPHY) of Pichia anomala
      in P. pastoris and its applicability in fractionating allergenic glycinin from
      soy protein.
AB  - The phytase (PPHY) of Pichia anomala has the requisite properties of
      thermostability and acidstability, broad substrate spectrum, and protease
      insensitivity, which make it a suitable candidate as a feed and food additive.
      The 1,389-bp PPHY gene was amplified from P. anomala genomic DNA, cloned in
      pPICZalphaA, and expressed extracellularly in P. pastoris X33. Three copies of
      PPHY have been detected integrated into the chromosomal DNA of the recombinant P.
      pastoris. The size exclusion chromatography followed by electrophoresis of the
      pure rPPHY confirmed that this is a homohexameric glycoprotein of ~420 kDa with a
      24.3 % portion as N-linked glycans. The temperature and pH optima of rPPHY are 60
      degrees C and 4.0, similar to the endogenous enzyme. The kinetic characteristics
      K(m), V(max), K(cat), and K(cat)/K(m) of rPPHY are 0.2 +/- 0.03 mM, 78.2 +/- 1.43
      nmol mg(-1) s(-1), 65,655 +/- 10.92 s(-1), and 328.3 +/- 3.12 MUM(-1) s(-1),
      respectively. The optimization of medium components led to a 21.8-fold
      improvement in rPPHY production over the endogenous yeast. The rPPHY titer
      attained in shake flasks could also be sustained in the laboratory fermenter. The
      rPPHY accounts for 57.1 % of the total secreted protein into the medium. The
      enzyme has been found useful in fractionating allergenic protein glycinin from
      soya protein besides dephytinization.

PMID- 24668020
TI  - Formation and control of line defects caused by tectonics of water droplet arrays
      during self-organized honeycomb-patterned polymer film formation.
AB  - This study describes the formation of macro-scale defects of the honeycomb
      patterned polymer film and we discovered two types of new line defects which
      differ from the defects reported in the past studies. We examined the formation
      mechanisms of the line defects and clarified two types of formation mechanisms of
      the "Divergent" mode line defects and the "Convergent" mode line defects caused
      by the "tectonics" of water droplet arrays on polymer solutions. The regions
      causing the macro-scale line defects are made clear in the phase diagram
      represented by the radius and the density of the micro-scale water droplets. In
      addition, the results of our calculations made it possible to theoretically
      predict the water droplet growth time for the water droplets to grow to the ideal
      size for uniform packing that is necessary for fabrication of the defect-free
      honeycomb-patterned polymer film. With the use of these techniques, A4-sized,
      defect-free, honeycomb-patterned polymer films can be fabricated. 

PMID- 24668019
TI  - Eco-friendly methodology for efficient synthesis and scale-up of 2-ethylhexyl-p
      methoxycinnamate using Rhizopus oryzae lipase and its biological evaluation.
AB  - Lipase-mediated synthesis of phenolic acid esters is a green and economical
      alternative to current chemical methods. Octyl methoxycinnamate, an important UVB
      absorbing compound, was synthesized by the esterification of p-methoxycinnamic
      acid with 2-ethyl hexanol using Rhizopus oryzae lipase. A molar ratio of 1:2 of p
      methoxycinnamic acid and 2-ethyl hexanol was found to give an optimum yield using
      cyclo-octane (50 ml) as reaction solvent, at a temperature of 45  degrees C, and
      750 U of lipase, resulting in a yield of 91.3 % in 96 h. This reaction was
      successfully scaled up to 400-ml reaction size where 88.6 %bioconversion was
      achieved. The synthesized compound was found to have superior antioxidant
      activity as compared to ascorbic acid. The synthesized compound also exhibited
      good antimicrobial activity against Escherichia coli, Klebsiella pneumonia,
      Salmonella typhi, Staphylococcus aures, Candida albicans (yeast), Aspergillus
      niger, Alternaria solani, and Fussarium oxysporum by well diffusion method in
      terms of zone of inhibitions (in mm).

PMID- 24668021
TI  - Ipragliflozin: first global approval.
AB  - Ipragliflozin (Suglat(r) [Japan]), an orally active, next-generation sodium
      glucose transporter 2 (SGLT2) inhibitor, has been developed by Astellas Pharma
      and Kotobuki Pharmaceutical for the treatment of type 2 diabetes mellitus.
      Ipragliflozin has received its first global approval in this indication in Japan,
      for use as monotherapy or in combination with another antihyperglycaemic agent
      (metformin, pioglitazone, a sulfonylurea, an alpha-glucosidase inhibitor, a
      dipeptidylpeptidase-4 inhibitor or nateglinide). Ipragliflozin is the first SGLT2
      inhibitor to be approved in Japan. This article summarizes the milestones in the
      development of ipragliflozin leading to this first approval for the treatment of
      type 2 diabetes mellitus.

PMID- 24668023
TI  - Toxicity and chemical analyses of airport runoff waters in Poland.
AB  - The aim of this study was to assess the ecotoxicological effects of various
      compounds in complex airport effluents using a chemical and ecotoxicological
      integrated strategy. The present work deals with the determination of sum of
      PCBs, PAHs, pesticides, cations, anions, phenols, anionic, cationic, non-ionic
      detergents, formaldehyde and metals--as well as TOC and conductivity--in runoff
      water samples collected from 2009 to 2011 at several locations on two Polish
      international airports. Two microbiotests (Vibrio fischeri bacteria and the
      crustacean Thamnocephalus platyurus) have been used to determine the ecotoxicity
      of airport runoff waters. The levels of many compounds exceeded several or even
      several tens of times the maximum permissible levels. Analysis of the obtained
      data shows that samples that displayed maximum toxicity towards the bioindicators
      Vibrio fischeri were not toxic towards Thamnocephalus platyurus. Levels of
      toxicity towards T. platyurus are strongly correlated with pollutants that
      originate from the technological operations related to the maintenance of airport
      infrastructure. The integrated (chemical-ecotoxicological) approach to
      environmental contamination assessment in and around airports yields extensive
      information on the quality of the environment. These methodologies can be then
      used as tools for tracking the environmental fate of these compounds and for
      assessing the environmental effect of airports. Subsequently, these data will
      provide a basis for airport infrastructure management.

PMID- 24668022
TI  - Absence Epilepsy: Older vs Newer AEDs.
AB  - OPINION STATEMENT: Over the last one to two decades, several new antiepileptic
      drugs (AEDs) have become available. These medications have different mechanisms
      of action, metabolism, efficacy, and side effect profiles. Hence, it has become
      possible to customize medications for a particular patient. It has also become
      possible to use various combinations of treatments for refractory epilepsies. As
      medication options have increased, our goal has shifted to not only to maximize
      seizure control but also to minimize side effects. However, the older AEDs are
      still widely used. So the question arises-are newer medications better than older
      AEDs for the treatment of absence epilepsy? Based on a large multicenter class I
      study, older AEDs-ethosuximide and valproic acid-are more efficacious than newer
      AEDs. Due to reduced side effects, ethosuximide remains the first line treatment
      for childhood absence epilepsy.

PMID- 24668025
TI  - Research ethics in global mental health: advancing culturally responsive mental
      health research.
AB  - Global mental health research is needed to inform effective and efficient
      services and policy interventions within and between countries. Ethical
      reflection should accompany all GMHR and human resource capacity endeavors to
      ensure high standards of respect for participants and communities and to raise
      public debate leading to changes in policies and regulations. The views and
      circumstances of ethno-cultural and disadvantaged communities in the Majority and
      Minority world need to be considered to enhance scientific merit, public
      awareness, and social justice. The same applies to people with vulnerabilities
      yet who are simultaneously capable, such as children and youth. The ethical
      principles of respect for persons or autonomy, beneficence/non-maleficence,
      justice, and relationality require careful contextualization for research
      involving human beings. Building on the work of Fisher and colleagues (2002),
      this article highlights some strategies to stimulate the ethical conduct of
      global mental health research and to guide decision-making for culturally
      responsible research, such as developing culturally sensitive informed consent
      and disclosure policies and procedures; paying special attention to
      socioeconomic, cultural, and environmental risks and benefits; and ensuring
      meaningful community and individual participation. Research and capacity-building
      partnerships, political will, and access to resources are needed to stimulate
      global mental health research and consolidate ethical practice. 

PMID- 24668024
TI  - Carvedilol induces greater control of beta2- than beta 1-adrenoceptor-mediated
      inotropic and lusitropic effects by PDE3, while PDE4 has no effect in human
      failing myocardium.
AB  - The beta-blockers carvedilol and metoprolol provide important therapeutic
      strategies for heart failure treatment. Therapy with metoprolol facilitates the
      control by phosphodiesterase PDE3, but not PDE4, of inotropic effects of
      catecholamines in human failing ventricle. However, it is not known whether
      carvedilol has the same effect. We investigated whether the PDE3-selective
      inhibitor cilostamide (0.3 MUM) or PDE4-selective inhibitor rolipram (1 MUM)
      modified the positive inotropic and lusitropic effects of catecholamines in
      ventricular myocardium of heart failure patients treated with carvedilol. Right
      ventricular trabeculae from explanted hearts of nine carvedilol-treated patients
      with terminal heart failure were paced to contract at 1 Hz. The effects of (-)
      noradrenaline, mediated through beta1-adrenoceptors (beta2-adrenoceptors blocked
      with ICI118551), and (-)-adrenaline, mediated through beta2-adrenoceptors (beta1
      adrenoceptors blocked with CGP20712A), were assessed in the absence and presence
      of the PDE inhibitors. The inotropic potency, estimated from -logEC50s, was
      unchanged for (-)-noradrenaline but decreased 16-fold for (-)-adrenaline in
      carvedilol-treated compared to non-beta-blocker-treated patients, consistent with
      the previously reported beta2-adrenoceptor-selectivity of carvedilol. Cilostamide
      caused 2- to 3-fold and 10- to 35-fold potentiations of the inotropic and
      lusitropic effects of (-)-noradrenaline and (-)-adrenaline, respectively, in
      trabeculae from carvedilol-treated patients. Rolipram did not affect the
      inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline.
      Treatment of heart failure patients with carvedilol induces PDE3 to selectively
      control the positive inotropic and lusitropic effects mediated through
      ventricular beta2-adrenoceptors compared to beta1-adrenoceptors. The beta2
      adrenoceptor-selectivity of carvedilol may provide protection against beta2
      adrenoceptor-mediated ventricular overstimulation in PDE3 inhibitor-treated
      patients. PDE4 does not control beta1- and beta2-adrenoceptor-mediated inotropic
      and lusitropic effects in carvedilol-treated patients.

PMID- 24668027
TI  - Self-assembly of octachloroperylene diimide into 1D rods and 2D plates by
      manipulating the growth kinetics for waveguide applications.
AB  - One-dimensional (1D) rods and 2D hexagonal plates of octachloroperylene diimide
      (Cl8-PTCDI) have been selectively prepared by controlling the growth kinetic
      processes. Both ensemble and single-particle spectroscopy clarify that 1D rods
      and 2D plates have shape dependent optical waveguiding properties. 

PMID- 24668026
TI  - Identification of candidate genes for Fusarium yellows resistance in Chinese
      cabbage by differential expression analysis.
AB  - Fusarium yellows caused by Fusarium oxysporum f. sp. conglutinans is an important
      disease of Brassica worldwide. To identify a resistance (R) gene against Fusarium
      yellows in Chinese cabbage (Brassica rapa var. pekinensis), we analyzed
      differential expression at the whole genome level between resistant and
      susceptible inbred lines using RNA sequencing. Four hundred and eighteen genes
      were significantly differentially expressed, and these were enriched for genes
      involved in response to stress or stimulus. Seven dominant DNA markers at
      putative R-genes were identified. Presence and absence of the sequence of the
      putative R-genes, Bra012688 and Bra012689, correlated with the resistance of six
      inbred lines and susceptibility of four inbred lines, respectively. In F(2)
      populations derived from crosses between resistant and susceptible inbred lines,
      presence of Bra012688 and Bra012689 cosegregated with resistance, suggesting that
      Bra012688 and Bra012689 are good candidates for fusarium yellows resistance in
      Chinese cabbage.

PMID- 24668028
TI  - Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via
      paracrine signalling.
AB  - Cancer stem cells (CSCs) are a promising target for treating cancer, yet how CSC
      plasticity is maintained in vivo is unclear and is difficult to study in vitro.
      Here we establish a sustainable primary culture of Oct3/4(+)/Nanog(+) lung CSCs
      fed with CD90(+) cancer-associated fibroblasts (CAFs) to further advance our
      knowledge of preserving stem cells in the tumour microenvironment. Using
      transcriptomics we identify the paracrine network by which CAFs enrich CSCs
      through de-differentiation and reacquisition of stem cell-like properties.
      Specifically, we find that IGF1R signalling activation in cancer cells in the
      presence of CAFs expressing IGF-II can induce Nanog expression and promote
      stemness. Moreover, this paracrine signalling predicts overall and relapse-free
      survival in stage I non-small cell lung cancer (NSCLC) patients. IGF-II/IGF1R
      signalling blockade inhibits Nanog expression and attenuates cancer stem cell
      features. Our data demonstrate that CAFs constitute a supporting niche for cancer
      stemness, and targeting this paracrine signalling may present a new therapeutic
      strategy for NSCLC. 

PMID- 24668029
TI  - Green synthesis of silver and gold nanoparticles using Zingiber officinale root
      extract and antibacterial activity of silver nanoparticles against food
      pathogens.
AB  - In the present study, we synthesized silver and gold nanoparticles with a
      particle size of 10-20 nm, using Zingiber officinale root extract as a reducing
      and capping agent. Chloroauric acid (HAuCl4) and silver nitrate (AgNO3) were
      mixed with Z. officinale root extract for the production of silver (AgNPs) and
      gold nanoparticles (AuNPs). The surface plasmon absorbance spectra of AgNPs and
      AuNPs were observed at 436-531 nm, respectively. Optimum nanoparticle production
      was achieved at pH 8 and 9, 1 mM metal ion, a reaction temperature 50  degrees C
      and reaction time of 150-180 min for AgNPs and AuNPs, respectively. An energy
      dispersive X-ray spectroscopy (SEM-EDS) study provides proof for the purity of
      AgNPs and AuNPs. Transmission electron microscopy images show the diameter of
      well-dispersed AgNPs (10-20 nm) and AuNPs (5-20 nm). The nanocrystalline phase of
      Ag and Au with FCC crystal structures have been confirmed by X-ray diffraction
      analysis. Fourier transform infrared spectroscopy analysis shows the respective
      peaks for the potential biomolecules in the ginger rhizome extract, which are
      responsible for the reduction in metal ions and synthesized AgNPs and AuNPs. In
      addition, the synthesized AgNPs showed a moderate antibacterial activity against
      bacterial food pathogens. 

PMID- 24668030
TI  - Simultaneous saccharification and fermentation of enzyme pretreated Lantana
      camara using S. cerevisiae.
AB  - Lantana camara, an abundantly available non-edible lignocellulosic biomass has
      been found to be a potential feedstock for ethanol production. The substrate was
      first pretreated with laccase followed by simultaneous saccharification and
      fermentation using cellulase and Saccharomyces cerevisiae, respectively. Laccase
      was produced from Pleurotus sp. and carbohydratases (cellulase and xylanase) were
      produced from Trichoderma reesei Rut C30. Using pretreated substrate simultaneous
      saccharification and fermentation was optimized through central composite design
      based response surface methodology. Maximum bioethanol concentration of 5.14 %
      (v/v) was obtained at optimum process conditions of substrate concentration 17 %
      (w/v), inoculum volume 9 % (v/v), inoculum age 60 and 144 h of incubation time.
      To enhance ethanol yield, S. cerevisiae was treated with ethyl methane sulfonate,
      a chemical mutagenic agent which induced mutagenesis. A maximum bioethanol
      concentration of 6.01 % (v/v) was obtained using the mutated strain of S.
      cerevisiae (CM5). 

PMID- 24668031
TI  - Aminosilanetrithiol RSi(SH)(3): an experimental and quantum-chemical study.
AB  - An interesting aminosilanetrithiol RSi(SH)3 (R = N(SiMe3)-2,6-iPr2C6H3) has been
      prepared by the reaction of lithium aminosilanetrithiolate {RSi[SLi(THF)]3}2 with
      MeCOOH. Theoretical calculations indicate that the LP(N) -> sigma*(Si-S) and
      LP(S) -> sigma*(Si-S) electron donations remarkably contribute to the
      stabilization of the Si(SH)3 part of the molecule. RSi(SH)3 is the first example
      of a stable molecule containing three SH groups attached to one element. 

PMID- 24668032
TI  - Methods of intraperitoneal local anaesthetic instillation for laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Intraperitoneal local anaesthetic instillation may decrease pain in
      people undergoing laparoscopic cholecystectomy. However, the optimal method to
      administer the local anaesthetic is unknown. OBJECTIVES: To determine the optimal
      local anaesthetic agent, the optimal timing, and the optimal delivery method of
      the local anaesthetic agent used for intraperitoneal instillation in people
      undergoing laparoscopic cholecystectomy. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science
      Citation Index Expanded, and the World Health Organization International Clinical
      Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised
      clinical trials for assessment of benefit and comparative non-randomised studies
      for the assessment of treatment-related harms. SELECTION CRITERIA: We considered
      only randomised clinical trials (irrespective of language, blinding, or
      publication status) comparing different methods of local anaesthetic
      intraperitoneal instillation during laparoscopic cholecystectomy for the review.
      DATA COLLECTION AND ANALYSIS: Two review authors collected the data
      independently. We analysed the data with both fixed-effect and random-effects
      models using Review Manager 5 analysis. For each outcome, we calculated the risk
      ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). MAIN
      RESULTS: We included 12 trials with 798 participants undergoing elective
      laparoscopic cholecystectomy randomised to different methods of intraperitoneal
      local anaesthetic instillation. All the trials were at high risk of bias. Most
      trials included only people with low anaesthetic risk. The comparisons included
      in the trials that met the eligibility criteria were the following; comparison of
      one local anaesthetic agent with another local anaesthetic agent (three trials);
      comparison of timing of delivery (six trials); comparison of different methods of
      delivery of the anaesthetic agent (two trials); comparison of location of the
      instillation of the anaesthetic agent (one trial); three trials reported
      mortality and morbidity.There were no mortalities or serious adverse events in
      either group in the following comparisons: bupivacaine (0/100 (0%)) versus
      lignocaine (0/106 (0%)) (one trial; 206 participants); just after creation of
      pneumoperitoneum (0/55 (0%)) versus end of surgery (0/55 (0%)) (two trials; 110
      participants); just after creation of pneumoperitoneum (0/15 (0%)) versus after
      the end of surgery (0/15 (0%)) (one trial; 30 participants); end of surgery (0/15
      (0%)) versus after the end of surgery (0/15 (0%)) (one trial; 30
      participants).None of the trials reported quality of life, the time taken to
      return to normal activity, or the time taken to return to work. The differences
      in the proportion of people who were discharged as day-surgery and the length of
      hospital stay were imprecise in all the comparisons included that reported these
      outcomes (very low quality evidence). There were some differences in the pain
      scores on the visual analogue scale (1 to 10 cm) but these were neither
      consistent nor robust to fixed-effect versus random-effects meta-analysis or
      sensitivity analysis. AUTHORS' CONCLUSIONS: The currently available evidence is
      inadequate to determine the effects of one method of local anaesthetic
      intraperitoneal instillation compared with any other method of local anaesthetic
      intraperitoneal instillation in low anaesthetic risk individuals undergoing
      elective laparoscopic cholecystectomy. Further randomised clinical trials of low
      risk of systematic and random errors are necessary. Such trials should include
      important clinical outcomes such as quality of life and time to return to work in
      their assessment.

PMID- 24668033
TI  - A phase II study of the gamma secretase inhibitor RO4929097 in patients with
      previously treated metastatic pancreatic adenocarcinoma.
AB  - PURPOSE: The notch pathway is overexpressed in pancreatic adenocarcinoma.
      RO4929097, an oral inhibitor of the gamma-secretase enzyme has been safely given
      as a single agent in patients with advanced solid tumors. We aimed to evaluate
      the efficacy of RO4929097 in patients with pancreatic adenocarcinoma (PDA).
      METHODS: A two-stage, single-arm Phase II trial was conducted in patients with
      previously treated metastatic PDA. RO4929097 was administered at a dose of 20 mg
      daily on days 1-3, 8-10 and 15-17 of 21-day cycles. The primary endpoint was
      survival at 6 months. Secondary endpoints included overall survival (OS),
      response rate, toxicities, pharmacokinetic and pharmacodynamic analyses. RESULTS:
      Eighteen patients were recruited, 17 in the first stage and one in the 2nd stage.
      It was decided to stop further enrollment after RO4929097 was discontinued by the
      sponsor and was no longer a development candidate. Three (25 %) of 12 evaluable
      patients achieved stable disease. The 6-month survival rate was 27.8 % (95 % CI
      9.7-53.5). The median OS was 4.1 months (95 % CI 2.7-5.8 months) and median
      progression-free survival was 1.5 months (95 % CI 1.3-1.6 months).
      Pharmacokinetic properties of RO4929097 in patients (n = 5) with PDA was similar
      to that previously reported in other patient populations. There was a trend
      towards a decrease in HeyL (p = 0.08) gene expression in three patients following
      study drug administration. CONCLUSIONS: RO4929097 was well-tolerated in patients
      with previously treated PDA. Development of RO4929097 has been discontinued, but
      development of other notch-targeting agents in pancreatic cancer is continuing.

PMID- 24668035
TI  - Structure and properties of bimetallic titanium and vanadium oxide clusters.
AB  - By employing a genetic algorithm together with density functional theory (B3LYP),
      we investigate the most stable minimum structures of several bimetallic titanium
      and vanadium oxide clusters that contain four metal atoms. The following
      compositions are studied: VnTin-4O10(-) (n = 1-4), (TiO2)VOn(-) (n = 1-4), and
      (TiO2)VOn(+) (n = 1-3). Apart from (TiO2)3VO(-), vanadium oxo groups are always
      part of the most stable minimum structures when vanadium is present. Anti
      ferromagnetic coupling lowers the energy substantially if spin centers are
      located at neighbored metal atoms rather than at distant oxygen radical sites.
      Vanadium-rich or oxygen-poor compositions prefer symmetric adamantane-like cage
      structures, some of which have already been proposed in a previous study. In
      contrast, vanadium-poor and oxygen-rich compositions show versatile structural
      motifs that cannot be intuitively derived from the symmetric cage motif.
      Particularly, for Ti4O10(-) there are several non-symmetric and distorted cages
      that have an up to 68 kJ mol(-1) lower energy than the symmetric adamantane-like
      cage structure. Nevertheless, for the adamantane-like cage the simulated infra
      red spectrum (within the harmonic approximation) agrees best with the
      experimental vibrational spectrum. The oxidative power of the (TiO2)3VO3(-) and
      (TiO2)3VO2(+) clusters as measured by the energy of removing 1/2 O2 (297 and 227
      kJ mol(-1), respectively) is less than that of the pure vanadium oxide clusters
      (V2O5)VO3(-) and (V2O5)VO2(+) (283 and 165 kJ mol(-1), respectively). 

PMID- 24668034
TI  - Treatment of hypertension in older persons: what is the evidence?
AB  - Evidence for treatment of hypertension in older people is limited to placebo
      controlled studies that reduced blood pressure in persons over 60 years who had
      systolic blood pressure >160 mmHg. Generally, physicians measure blood pressure
      poorly, failing to look for white coat or masked hypertension, orthostasis,
      postprandial hypotension, or pseudohypertension. There is evidence that if 24
      hour ambulatory blood pressures were obtained, the treatment goal should be
      substantially lower. Sleep apnea, pain, nocturnal hypoglycemia, drugs, excess
      aldosterone production, and pheochromocytoma should all be considered as causes
      of hypertension in older persons. Evidence supports a low-dose diuretic or an
      angiotensin converting enzyme inhibitor as appropriate first-line therapies in
      older persons.

PMID- 24668037
TI  - Rapid antidepressant effects and abuse liability of ketamine.

PMID- 24668036
TI  - Smoking improves divided attention in schizophrenia.
AB  - RATIONALE: Smoking is highly prevalent in schizophrenia, and there is evidence
      for beneficial effects on neurocognition. Smoking is therefore hypothesized a
      self-medication in schizophrenia. Although much effort is devoted to characterize
      those cognitive domains that potentially benefit from smoking, divided attention
      has not yet been investigated. OBJECTIVES: The aim of this study was to analyze
      the interactional effects of diagnosis of schizophrenia and smoking history on
      divided attention. METHODS: We investigated behavioral measures of divided
      attention in a sample of 48 schizophrenic patients and 48 controls (24 current
      smokers and non-smokers each) carefully matched for age, sex, education, verbal
      IQ, and smoking status with general linear models. RESULTS: Most important within
      the scope of this study, significant interactions were found for valid reactions
      and errors of omission: Performance substantially increased in smoking
      schizophrenic patients, but not in controls. Further, these interactions were
      modified by sex, driven by female schizophrenic patients who showed a significant
      behavioral advantage of smokers over non-smokers, other than male schizophrenic
      patients or healthy controls who did not express this sex-specific pattern.
      CONCLUSIONS: Results suggest a positive effect of smoking history on divided
      attention in schizophrenic patients. This study provides first evidence that the
      complex attention domain of divided attention is improved by smoking, which
      further substantiates the self-medication hypothesis of smoking in schizophrenia,
      although this has been shown mainly for sustained and selective attention. Gender
      specific effects on cognition need to be further investigated.

PMID- 24668038
TI  - The (lack of) impact of retraction on citation networks.
AB  - Article retraction in research is rising, yet retracted articles continue to be
      cited at a disturbing rate. This paper presents an analysis of recent retraction
      patterns, with a unique emphasis on the role author self-cites play, to assist
      the scientific community in creating counter-strategies. This was accomplished by
      examining the following: (1) A categorization of retracted articles more complete
      than previously published work. (2) The relationship between citation counts and
      after-retraction self-cites from the authors of the work, and the distribution of
      self-cites across our retraction categories. (3) The distribution of retractions
      written by both the author and the editor across our retraction categories. (4)
      The trends for seven of our nine defined retraction categories over a 6-year
      period. (5) The average journal impact factor by category, and the relationship
      between impact factor, author self-cites, and overall citations. Our findings
      indicate new reasons for retractions have emerged in recent years, and more
      editors are penning retractions. The rates of increase for retraction varies by
      category, and there is statistically significant difference of average impact
      factor between many categories. 18 % of authors self-cite retracted work post
      retraction with only 10 % of those authors also citing the retraction notice.
      Further, there is a positive correlation between self-cites and after retraction
      citations. 

PMID- 24668039
TI  - Influence of temperature and organic solvents (isopropanol and 1,4-dioxane) on
      the micellization of cationic gemini surfactant (14-4-14).
AB  - The micellar properties of gemini surfactant, tetramethylene-1,4
      bis(dimethyltetradecylammonium bromide) (14-4-14) in binary aqueous mixtures of
      isopropanol (IP) and 1,4-dioxane (DO) were investigated by tensiometric,
      conductometric and microcalorimetric methods in the temperature range of 298 to
      323 K. The values of both critical micelle concentration (cmc) and degree of
      dissociation increase with increasing temperature and concentration of cosolvent.
      The energetics of micellization was determined from the temperature dependence of
      critical micelle concentration values. The standard Gibbs free energy of
      micellization (DeltaG) was found to be negative and the negative value decreases
      with both temperature and concentration of cosolvent. The Gibbs free energy of
      micellization (DeltaG) is mainly controlled by tail transfer free energy. The
      enthalpy of micellization obtained from direct calorimetry, Gibbs-Helmholtz
      equation and van't Hoff methods are presented and compared. Entropic contribution
      is found to be larger than the enthalpy and for all the systems, an enthalpy
      entropy compensation phenomenon was obtained. Some interfacial parameters, e.g.,
      Gibbs surface excess (Gammamax), minimum area per surfactant molecule (Amin),
      surface pressure (Picmc) were been calculated. The fluorimetric technique was
      used to understand the microenvironment of the solution under the influence of
      cosolvent. The micellar aggregation number of 14-4-14 in a binary mixed solvent
      was also determined from fluorimetry using pyrene as a probe. Two fluorophores,
      fluorescein and curcumin delivered the information of the peripheral region of
      the micellar interface and palisade region. The self-diffusion coefficients of
      the micellar media were evaluated using the cyclic voltammetry (CV) method. Such
      multi-technique investigation provides a new look into the role of solvation in
      micellization. 

PMID- 24668040
TI  - Development and validation of S-allyl-L-cysteine in rat plasma using a mixed-mode
      reversed-phase and cation-exchange LC-ESI-MS/MS method: application to
      pharmacokinetic studies.
AB  - S-Allyl-L-cysteine (SAC), the most abundant organosulfur compound derived from
      garlic, has multifunctional biological activities that occur via different
      mechanisms. A sensitive, rapid and simple LC-ESI-MS/MS method using a mixed-mode
      reversed-phase and cation-exchange column containing C18 silica particles and
      sulfonic acid cation-exchange particles has been developed and validated for the
      analysis of SAC in rat plasma. The mobile phase was optimized at 2 mM ammonium
      acetate buffer (pH = 3.5) and acetonitrile (75:25, v/v). The assay utilized 0.6%
      acetic acid in methanol to achieve simple and rapid deproteinization.
      Quantification was conducted using multiple reaction monitoring (MRM) of the
      transitions of m/z 162.0 -> 145.0 for SAC. The standard curve for SAC was linear
      (r(2) >= 0.999) over a range from 5 to 2,500 ng/mL. The intra- and interday
      precision (relative standard deviation) of the method was not >6.0% at three
      quality control levels. The limit of quantification (LOQ) was 5.0 ng/mL. After
      being fully validated, the method was successfully applied to the pharmacokinetic
      monitoring of SAC in rat plasma.

PMID- 24668041
TI  - Analysis of volatile compounds from Siraitia grosvenorii by headspace solid-phase
      microextraction and gas chromatography-quadrupole time-of-flight mass
      spectrometry.
AB  - Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography
      quadrupole time-of-flight mass spectrometry (GC-QTOF MS) has been used in the
      present study to isolate and identify volatile components from Siraitia
      grosvenorii, a herbaceous perennial vine used as a natural sweetener and
      medicine. Compared with the static HS extraction and the different SPME fiber
      coatings, HS-SPME with divinylbenzene/carboxen/polydimethylsiloxane fiber was
      preferred to extract the target analytes including aldehyde, alcohol, acid, ester
      and other compounds. In the identification, a multi-dimensional qualitative
      analysis approach containing library searching, retention index comparison,
      accurate mass measurement, the second-stage mass spectrum (MS(2) spectrum) and
      area normalization was utilized. Finally, a total of 46 compounds were identified
      from S. grosvenorii. Among them, n-hexadecanoic acid, 5-hydroxymethylfurfural,
      2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, (Z, Z)-9,12-octadecadienoic
      acid and (E, E)-2,4-nonadienal were the main volatile components. The results
      showed that HS-SPME coupled with GC-QTOF MS is efficient for the extraction of
      polar volatiles from S. grosvenorii and accurate for the identification of
      volatile compounds in the complicated matrix. 

PMID- 24668042
TI  - High-throughput ultra-performance LC-MS-MS method for analysis of diclofenac
      sodium in rabbit plasma.
AB  - A new UPLC-MS-MS method was developed and validated for quantification of
      diclofenac sodium in rabbit plasma. Acetonitrile-based protein precipitation
      method was used to extract the drug from plasma samples. Chromatographic
      separation was carried out on Acquity UPLC((r))BEH phenyl C18 1.7 um, 2.1 * 50 mm
      column. Drug elution was facilitated by using mobile phase containing
      acetonitrile (0.1% glacial acetic) and water (pH 3.5), in a ratio of 75 : 25,
      flowing at 0.2 mL/min. Molecular ions were generated by using the positive
      electrospray ionization mode (ESI(+)) and analyzed on a triple-quadrupole mass
      spectrometer. The ionic transitions of diclofenac (m/z 296 > 214 and 249.9) and
      flufenamic acid (internal standard) (m/z 282.1 > 166.9 and 244) were measured in
      multiple reaction modes. Developed method is simple, quick, precise and accurate
      over a linearity range of 80-4,000 ng/mL. The lower limit of quantification
      (LLOQ) for diclofenac was 80 ng/mL. The percentage recoveries of diclofenac at
      three quality control samples were 54 +/- 6.1, 67.1 +/- 5.4 and 62.3 +/- 1.4%.
      Precision and accuracy of the assay at LLOQ, middle limit of quantitation and
      higher limit of quantitation were 100 +/- 7.0, 100 +/- 1.0 and 100 +/- 2.0% and
      81.8 +/- 4.6, 106.6 +/- 3.1 and 103.3 +/- 4.0%, respectively. 

PMID- 24668043
TI  - Determination of phosphodiesterase-5 inhibitors and analogs using high
      performance liquid chromatography with ultraviolet detection.
AB  - A considerable number of erectile dysfunction products, and dietary supplements
      suspected of containing phosphodiesterase-5 (PDE-5) inhibitors, have been
      analyzed by the US Food and Drug Administration. Often these samples are found to
      contain the approved active pharmaceutical ingredients (APIs) such as sildenafil,
      tadalafil or vardenafil. However, analogs of these APIs have also been identified
      in many samples and products containing multiple PDE-5 inhibitors have also been
      found. A single high-performance liquid chromatography with ultraviolet detection
      method has been developed for the determination of sildenafil, tadalafil,
      vardenafil and a number of commonly encountered analogs in pharmaceutical dosage
      forms and dietary supplement products, including tablets, capsules, bulk powders,
      troches and liquids. This method was designed as an alternative to methods
      developed for the determination of a single PDE-5 inhibitor. Using this protocol,
      14 PDE-5 inhibitor compounds can be separated and determined in a single
      analysis. 

PMID- 24668044
TI  - Tin-catalyzed conversion of biomass-derived triose sugar and formaldehyde to
      alpha-hydroxy-gamma-butyrolactone.
AB  - The direct conversion of biomass-derived 1,3-dihydroxyacetone (DHA) and
      formaldehyde to alpha-hydroxy-gamma-butyrolactone (HBL) was achieved through the
      use of tin(iv) chloride and a small amount of water and the yield reached up to
      70%. The reaction mechanism was also investigated by incorporating d2
      formaldehyde into the reaction mixtures. 

PMID- 24668045
TI  - Management of acute and chronic vascular conditions of the hand.
AB  - Management of acute and chronic vascular disorders of the hand in patients with
      vasospastic and vaso-occlusive disorders is a complex problem and requires a
      multidisciplinary approach. The ischemia-related pain, skin ulcerations, and
      ultimately the threat of digital gangrene require a concerted effort to improve
      perfusion using a combination of medications and surgery. The purpose of this
      work is to review our experience over the past 2 decades with this cohort of
      patients including the variability of the clinical presentation, a method of
      classification, and a practical treatment philosophy. 

PMID- 24668046
TI  - Occurrence and removal of benzotriazole ultraviolet stabilizers in a wastewater
      treatment plant in China.
AB  - Benzotriazole ultraviolet stabilizers (BZT-UVs) have previously been found in
      sludge from wastewater treatment plants (WWTPs), which might be potential sources
      of BZT-UVs to the surrounding environment. In this work, the occurrence and fate
      of seven emerging 2-hydroxyphenyl substituted BZT-UVs were investigated in a
      Chinese WWTP. This group of hydrophobic BZT-UVs possess log Kow values ranging
      from 4.31 to 7.67 which could be associated with their fate in WWTPs. Field
      samples including 24 h flow composites of influent, effluent and grab sludge
      samples from different treatment processes were collected and analyzed.
      Concentrations of BZT-UVs dissolved in aqueous-phases were in the range of 4.88+/
      1.35 (UV-234) to 34.5+/-12.4 ng L(-1) (UV-P) in the primary influent, while only
      UV-P and UV-328 were detected in the final effluent at concentrations of 10.5+/
      6.59 and 2.74+/-1.73 ng L(-1), respectively. Considering the amount of target BZT
      UVs adsorbed to total suspended solids (TSS), the daily mass flux in the primary
      influent of the WWTP ranged from 22.3 g day(-1) (UV-P, 7.99%) to 74.0 g day(-1)
      (UV-234, 26.5%). Total removal efficiency of the integrated treatment process
      ranged from 89.7% for UV-P to 99.7% for UV-234 suggesting nearly complete
      removal. Organic solid sedimentation in primary and secondary clarifiers was the
      dominant elimination route for BZT-UV analogues, which constituted 96.3% of the
      total removal efficiency. Advanced treatment (using ultraviolet disinfection) in
      this plant might further contribute to the high removal efficiencies (ranging
      from 19.6% to 77.3%).

PMID- 24668047
TI  - Legal responsibilities of physicians when making participation decisions in
      athletes with cardiac disorders: Do guidelines provide a solid legal footing?
AB  - Safe sports participation involves protecting athletes from injury and life
      threatening situations. Preparticipation cardiovascular screening (PPS) in
      athletes is intended to prevent exercise-related sudden cardiac death by medical
      management of athletes at risk, which may include disqualification from sports
      participation. The screening physician relies on current guidelines and expert
      recommendations for management and decision-making. There is concern about false
      positive screening results and wrongly grounding an athlete. Similarly, there is
      a concern about false-negative screening results and athletes participating with
      potentially lethal disorders. Who is legally responsible if an athlete suddenly
      dies after a proper PPS resulting in low risk? Several consensus documents based
      on expert opinion describe only a few lines on legal responsibilities in
      eligibility screening and disqualification decision-making in athletes. This
      article discusses legal responsibilities and concerns in eligibility decision
      making for physicians. 

PMID- 24668048
TI  - Smartphone and tablet apps for concussion road warriors (team clinicians): a
      systematic review for practical users.
AB  - BACKGROUND: Mobile technologies are steadily replacing traditional assessment
      approaches for the recognition and assessment of a sports concussion. Their ease
      of access, while facilitating the early identification of a concussion, also
      raises issues regarding the content of the applications (apps) and their
      suitability for different user groups. AIM: To locate and review apps that assist
      in the recognition and assessment of a sports concussion and to assess their
      content with respect to that of internationally accepted best-practice
      instruments. METHODS: A search of international app stores and of the web using
      key terms such as 'concussion', 'sports concussion' and variants was conducted.
      For those apps meeting the inclusion criteria, data were extracted on the
      platform, intended users and price. The content of each app was benchmarked to
      the Sport Concussion Assessment Tool 2 (SCAT2) and Pocket SCAT2 using a custom
      scoring scheme to generate a percentage compliance statistic. RESULTS: 18 of the
      155 apps identified met the inclusion criteria. Almost all (16/18) were available
      on an iOS platform and only five required a payment to purchase. The apps were
      marketed for a wide range of intended users from medical professionals to the
      general public. The content of the apps varied from 0% to 100% compliance with
      the selected standard, and 'symptom evaluation' components demonstrated the
      highest level of compliance. CONCLUSIONS: The surge in availability of apps in an
      unregulated market raises concerns as to the appropriateness of their content for
      different groups of end users. The consolidation of best-practice concussion
      instruments now provides a framework to inform the development of future apps.

PMID- 24668049
TI  - Narrowing the gap between the number of athletes who dope and the number of
      athletes who are caught: scientific advances that increase the efficacy of
      antidoping tests.
AB  - The analytical methods developed and applied by the antidoping laboratories have
      been continuously evolving over the past 50 years, with the aim of keeping pace
      with the constant evolution of doping strategies. Despite this, the number of
      adverse analytical tests reported worldwide by the network of the WADA-accredited
      laboratories still seems to underestimate the actual number of doped athletes. We
      investigate the most likely causes for this gap between the likely doping rate
      and the detection of athletes with positive doping tests. We consider laboratory
      and non-laboratory reasons that contribute to this gap. More specifically,
      laboratory issues are focused not only on those doping practices that may still
      be 'invisible' at the time of a doping test, but also on the possible role of non
      conventional masking strategies. These include (1) the intake of banned drugs by
      specific novel drug delivery systems and (2) the coadministration of prohibited
      and non-prohibited drugs, taking advantage of the capacity of the latter to
      affect the metabolism, and consequently the detection, of the former. Non
      laboratory issues include the lack of a sufficient level of 'intelligent
      testing', with the result that, even in the cases of doped athletes, the
      biological samples delivered to the antidoping laboratories for analysis may not
      contain those target analytes whose detection (and if necessary quantification
      above a decision limit) constitutes an adverse analytical finding. We present
      proposals to improve the efficacy of the doping control policies based on the
      analysis of biological samples and suggest how to constantly keep up with the
      continuous developments of new forms of doping. 

PMID- 24668050
TI  - Football for life versus antidoping for the masses: ethical antidoping issues and
      solutions based on the extenuating experiences of an elite footballer competing
      while undergoing treatment for metastatic testicular cancer.
AB  - It is thankfully rare for extenuating circumstances to fully test the processes
      and procedures enshrined in national and world antidoping authorities' rules and
      laws. It is also thankfully very rare that a failed drugs test can have some
      positive implications. Antidoping laws are undoubtedly focused on ensuring fair
      competition, however, there are occasions when honest athletes discover medical
      diagnoses through failed antidoping tests. The purpose of this paper is to
      broadly discuss antidoping considerations encountered, based on the four
      principles of medical ethics and to propose simple solutions to these problems.
      Unfortunately, extreme medical circumstances will often test the limits of
      antidoping and medical processes and with open channels for feedback, these
      systems can improve. Performance enhancement seems an illogical concept if an
      athlete's medical treatment and disease are more inherently performance harming
      than unintended potential doping, but needs to be carefully managed to maintain
      fair sport. 

PMID- 24668051
TI  - A turn-on fluorescent Fe(3+) sensor derived from an anthracene-bearing bisdiene
      macrocycle and its intracellular imaging application.
AB  - Integrating N(2)-hydroxyethyldiethylenetriamine with anthracene gives a [2+2]
      macrocycle fluorescent sensor. This sensor displays an instant/reversible turn-on
      response specific to Fe(3+), which allows facile visualization of the
      Fe(3+)/Fe(2+) transition and intracellular Fe(3+) imaging. 

PMID- 24668052
TI  - Sex-specific characteristics of anthropometry in patients with obstructive sleep
      apnea: neck circumference and waist-hip ratio.
AB  - OBJECTIVE: This study aimed to investigate the sex-specific effects of
      anthropometric profiles on the occurrence and severity of obstructive sleep apnea
      (OSA). METHODS: We evaluated 151 patients with suspected OSA undergoing
      polysomnography and anthropometric measurements such as body mass index (BMI),
      neck and waist circumference (NC and WC), and waist-hip ratio (WHR). RESULTS: In
      men, NC (P = .006), WC (P = .035), and WHR (P = .003) were significantly
      increased in OSA and all were significantly correlated with apnea hypopnea index
      (AHI). However, in female OSA patients, BMI (P = .05), WC (P = .008), and WHR (P
      = .001) were elevated, but only WHR was significantly correlated with AHI.
      Correlation analyses showed significant correlations between NC and other
      anthropometric indexes in men but not in women. The receiver operating
      characteristic curves revealed that NC and WHR in men, and WHR in women, were
      significant in both model I (AHI > or = 5) and model 2 (AHI > or = 15).
      CONCLUSION: Waist-hip ratio is the most reliable correlate of OSA in both sexes.
      Neck circumference is an independent risk factor for male, but not for female,
      OSA patients. These different aspects of obesity may contribute to the
      pathogenesis of OSA and provide helpful guidance in the screening of OSA.

PMID- 24668053
TI  - Superomedial submucosal partial arytenoidectomy for improved posterior glottic
      closure: surgical technique and case presentation.
AB  - OBJECTIVE: Endoscopic medial partial arytenoidectomy has been described
      previously for expansion of the posterior glottic airway in bilateral vocal fold
      paralysis. Superomedial submucosal partial arytenoidectomy (SSPA), a modification
      of this technique, can improve glottic closure in the setting of an obstructing
      anteromedially prolapsed arytenoid. We present our surgical technique and a case
      example. METHODS AND RESULTS: A 45-year-old man presented with dysphonia
      attributable to unilateral true vocal fold paralysis. Laryngoscopy revealed right
      true vocal fold atrophy and an anteriorly prolapsed right arytenoid cartilage
      preventing posterior glottic closure during adduction. Right SSPA and ipsilateral
      vocal fold injection augmentation were performed without complication. One-month
      and 11-month postoperative evaluations showed marked improvement in voice, with
      complete glottic closure. Quality-of-life assessment and patient report showed a
      durable result at 50 months. CONCLUSION: SSPA may be a valuable technique in the
      management of breathy dysphonia associated with posterior glottic gap and other
      sequelae of the malpositioned arytenoid.

PMID- 24668054
TI  - Esthesioneuroblastoma: updating histologic grading as it relates to prognosis.
AB  - OBJECTIVE: The Hyams grading system has been extensively used to predict
      prognosis in patients with esthesioneuroblastoma (ENB). However, most studies
      showing prognostic correlation group grading into I/II versus III/IV, essentially
      comparing low versus high grade. In addition, these studies include patients with
      variable treatment regimens, including some that were treated with chemoradiation
      alone. We aimed to determine whether additional histologic variables correlate
      with outcome with regard to disease free and overall survival in a series of
      patients universally treated with anterior skull base resection and +/- adjuvant
      chemoradiation. STUDY DESIGN: A retrospective review of 27 patients with ENB was
      performed. METHODS: The sections of tumor from these 27 patients were studied and
      reviewed with attention to percentage lobularity, degree of pleomorphism, degree
      of neurofibrillary matrix, and degree of apoptosis. In addition, the presence or
      absence of rosettes, necrosis, calcification, spindle cells, gland hyperplasia,
      and bone invasion were noted. Finally, the number of mitoses per high power field
      and the nature of chromatin (fine vs coarse) were recorded. The histopathologic
      features of these 27 ENBs were reviewed and correlated with clinical outcome.
      RESULTS: There were 11 patients with recurrence (40.7% recurrence). There were 5
      deaths (81.5% survival). The study cohort's mean overall survival was 158 months
      and the mean disease-free survival was 70.6 months. In terms of overall survival,
      necrosis and mitosis (#/10hpf) were significant but not when multivariate
      analysis was performed, these were not individually significant. In terms of
      disease-free survival, mitosis (#/10hpf) was significant but not on multivariate
      analysis. Gland hyperplasia was found to be a positive prognostic variable,
      associated with longer overall and disease-free survival, but only in combination
      with no spindle features and without necrosis. CONCLUSIONS: An updated histologic
      grading system may provide more valuable prognostic information in patients with
      esthesioneuroblastoma treated with a standardized treatment paradigm.

PMID- 24668055
TI  - Laryngeal mask airways and use of a Boyle-Davis gag in ENT surgery: is there a
      learning curve? A prospective analysis.
AB  - OBJECTIVES: The objective was to identify whether the experience of the operating
      surgeon was relevant to the frequency of the laryngeal mask airway (LMA) airway
      obstruction or change to an endotracheal tube during ear, nose, and throat
      surgery. METHODS: Data were prospectively collected for 186 patients undergoing a
      procedure with the use of a Boyle-Davis gag and LMA over 12 months in a district
      general hospital in the United Kingdom. patient demographics (age, mallampati
      grade), grade of surgeon, grade of anesthetist, LMA size inserted, and any
      intraoperative adjustments needed were recorded. RESULTS: There was an overall
      intraoperative airway intervention rate of 21%. The experience of the surgeon
      affected the rate of intraoperative airway interventions encountered, reflected
      by the significantly lower rate of airway complications (ie, 10%) seen when
      associate specialists perform these types of procedures compared to other grades
      of surgeon (Fisher's exact test 2-tailed P value = .04). A significant
      complication rate of 50% was seen with core surgical trainees compared to other
      grades of surgeon (Fisher's exact test 2-tailed P value = .002). CONCLUSIONS: The
      results of this study suggest there may be a learning curve for otolaryngology
      trainees when using a LMA. However, larger studies and further subanalyses are
      essential before further conclusions can be made.

PMID- 24668056
TI  - Micronucleus frequency in human peripheral blood lymphocytes as a biomarker for
      the early detection of colorectal cancer risk.
AB  - The early detection of colorectal cancer (CRC) can significantly improve the
      prognosis of affected patients. The loss of genomic stability and the resulting
      gene alteration play an important role in the molecular pathological steps that
      occur early in tumorigenesis of CRC. Thus, the identification of non-invasive
      biomarkers, whose function may provide useful insights into critical early events
      in the CRC process, is of great interest. In this regard, micronucleus (MN)
      frequency in peripheral blood lymphocytes (PBL) has become one of the most
      established biomarkers for studying DNA damage in the human population. This
      study investigated the MN frequency in the PBL of 82 subjects (30 females and 52
      males; aged 50-70 years) who were participating in a screening programme for CRC
      prevention. All 82 patients were positive in fecal occult blood tests and they
      were subsequently classified, according to colonoscopy and histological findings,
      as patients with CRC, patients with colon polyps or subjects without intestinal
      lesion, referred to as study controls. This study also examined the relationship
      between the plasma clastogenic activity and the frequency of micronuclei of the
      study population. The MN frequency was significantly higher in CRC patients than
      in both colon polyp patients (16.82+/-6.56 versus 12.23+/-1.88; P = 0.002) and
      controls (16.82+/-6.56 versus 8.00+/-1.77; P < 0.001). An increased MN frequency
      was detected in the lymphocytes of the polyp group in comparison to the control
      group, although this was lower than that observed in CRC patients (12.23+/-1.88
      versus 8.00+/-1.77; P < 0.001). In the overall study population, the increase of
      MN frequency, which was observed in the lymphocytes of the subjects involved, was
      significantly associated with the clastogenic activity detected in their plasma
      (r = 0.594, P < 0.001). Overall, the results suggest that the MN test can become
      a promising biomarker for the early detection of CRC. 

PMID- 24668057
TI  - A modified technique for Gore Excluder limb deployment in difficult iliac anatomy
      during endovascular abdominal aortic aneurysm repair.
AB  - Complex iliac anatomy including extreme tortuosity constitutes a relative
      contraindication for endovascular abdominal aortic aneurysm repair with
      additional risk of limb-graft occlusion. The Gore Excluder limb-graft is a
      flexible stent-graft, which adapts easily to iliac tortuosity. Nevertheless, the
      presence of the stiff guide wire does not always allow for an ideal apposition of
      the stent graft to the angulated common iliac artery vessel wall. We describe
      herein a modified technique for Gore Excluder limb-graft deployment with partial
      removal of the stiff wire in cases with difficult tortuous or narrow iliac
      arteries during endovascular abdominal aortic aneurysm repair. 

PMID- 24668058
TI  - Indirect surgical management of a penetrating vertebral artery injury.
AB  - INTRODUCTION: Vertebral artery injury caused by penetrating neck trauma is a rare
      occurrence. Direct surgical repair is difficult due to anatomy and exposure.
      Proximal and distal ligation or/and embolization represent the most common
      management in cases which require intervention. CASE REPORT: A young man
      accidentally stabbed in the neck was admitted to the emergency department with
      active arterial bleeding from the wound. Immediate surgical exploration revealed
      an isolated injury of the left vertebral artery intraosseous segment. Lesion was
      managed by proximal segment ligature and distal Fogarty catheter balloon
      tamponade. Postoperative angiography excluded the need for further interventions.
      Balloon-catheter was successfully extracted after 72 hours and patient discharged
      neurologically intact on postoperative day 7. Fourteen months later, there are no
      signs of vascular or neurologic complications. CONCLUSION: Balloon-tamponade is a
      valuable technical adjunct in either temporizing or definitive management of
      surgically inaccessible vascular trauma.

PMID- 24668059
TI  - Placental ischemia induces changes in gene expression in chorionic tissue.
AB  - Preeclampsia is a serious and common hypertensive complication of pregnancy,
      affecting ~5 to 8 % of pregnancies. The underlying cause of preeclampsia is
      believed to be placental ischemia, which causes secretion of pathogenic factors
      into the maternal circulation. While a number of these factors have been
      identified, it is likely that others remain to be elucidated. Here, we have
      utilized a relevant preclinical rodent model of placental ischemia-induced
      hypertension, the reduced uterine perfusion pressure (RUPP) model, to determine
      the effect of chronic placental ischemia on the underlying chorionic tissue and
      placental villi. Tissue from control and RUPP rats were isolated on gestational
      day 19 and mRNA from these tissues was subjected to microarray analysis to
      determine differential gene expression. At a statistical cutoff of p < 0.05, some
      2,557 genes were differentially regulated between the two groups. Interestingly,
      only a small subset (22) of these genes exhibited changes of greater than 50 %
      versus control, a large proportion of which were subsequently confirmed using qRT
      PCR analysis. Network analysis indicated a strong effect on inflammatory
      pathways, including those involving NF-kappaB and inflammatory cytokines. Of the
      most differentially expressed genes, the predominant gene classes were
      extracellular remodeling proteins, pro-inflammatory proteins, and a coordinated
      upregulation of the prolactin genes. The functional implications of these novel
      factors are discussed. 

PMID- 24668061
TI  - The effect of Burns & Wounds (B&W)/burdock leaf therapy on burn-injured Amish
      patients: a pilot study measuring pain levels, infection rates, and healing
      times.
AB  - PURPOSE: The purposes of this pilot study were to measure pain associated with
      dressing changes, assess the presence of infection, and document healing times of
      burn-injured Amish in central Ohio using an herbal therapy consisting of Burns
      and WoundsTM ointment (B&W) and burdock (Arctium ssp.) leaves. B&W contains
      honey, lanolin, olive oil, wheat germ oil, marshmallow root, Aloe vera gel,
      wormwood, comfrey root, white oak bark, lobelia inflata, vegetable glycerin, bees
      wax, and myrrh. DESIGN: A prospective, case series design guided the study within
      a community-based participatory research framework. METHODS: Amish burn dressers
      provided burn care. Registered nurses monitored each case and documented
      findings. Pain scores were noted and burns were inspected for infection during
      dressing changes; healing times were measured from day of burn to complete
      closure of the skin. All cases were photographed. RESULTS: Between October 2011
      and May 2013, five Amish were enrolled. All had first- and second-degree burns.
      B&W/burdock leaf dressing changes caused minimal or no pain; none of the burns
      became infected, and healing times averaged less than 14 days. CONCLUSION AND
      IMPLICATIONS: The use of this herbal remedy appears to be an acceptable
      alternative to conventional burn care for these types of burns. The trauma of
      dressing changes was virtually nonexistent. Nurses working in communities with
      Amish residents should be aware of this herbal-based method of burn care and
      monitor its use when feasible.

PMID- 24668060
TI  - Sex differences in health and mortality in Moscow and Denmark.
AB  - In high income countries females outlive men, although they generally report
      worse health, the so-called male-female health-survival paradox. Russia has one
      of the world's largest sex difference in life expectancy with a male disadvantage
      of more than 10 years. We compare components of the paradox between Denmark and
      Moscow by examining sex differences in mortality and several health measures. The
      Human Mortality Database and the Russian Fertility and Mortality Database were
      used to examine sex differences in all-cause death rates in Denmark, Russia, and
      Moscow in 2007-2008. Self-reported health data were obtained from the Study of
      Middle-Aged Danish Twins (n = 4,314), the Longitudinal Study of Aging Danish
      Twins (n = 4,731), and the study of Stress, Aging, and Health in Russia (n =
      1,800). In both Moscow and Denmark there was a consistent female advantage at
      ages 55-89 years in survival and a male advantage in self-rated health, physical
      functioning, and depression symptomatology. Only on cognitive tests males
      performed similarly to or worse than women. Nevertheless, Muscovite males had
      more than twice higher mortality at ages 55-69 years compared to Muscovite women,
      almost double the ratio in Denmark. The present study showed that despite similar
      directions of sex differences in health and mortality in Moscow and Denmark, the
      male-female health-survival paradox is very pronounced in Moscow suggesting a
      stronger sex-specific disconnect between health indicators and mortality among
      middle-aged and young-old Muscovites.

PMID- 24668062
TI  - Delivering Mental Health Services to OEF/OIF Veterans: A VHA Qualitative Study.
AB  - PURPOSE: Veterans Health Administration (VHA) mental health (MH) professionals
      are providing care to increasing numbers of veterans who served in Operation
      Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). This study aimed to
      describe MH clinicians' views of OEF/OIF veteran needs and how providers meet
      those needs within a large system of care. DESIGN: Qualitative research
      methodology, specifically qualitative description, was used to explore VHA MH
      clinicians' experiences providing MH services to OEF/OIF veterans. METHODS:
      Thirteen VA MH providers participated in semistructured interviews, which
      included questions regarding the following areas: psychiatric needs of OEF/OIF
      veterans; collaboration and referral; needs and resources; and the
      personal/professional impact of providing services to this cohort. FINDINGS:
      Themes emerged which highlighted complex challenges faced by OEF/OIF veterans,
      barriers associated with matching the unique needs of these veterans with
      existing treatments, and the challenges and rewards associated with providing
      care to members of this population. CONCLUSIONS: Capturing provider perspectives
      within MH services suggest potential areas for innovation aimed at providing
      patient-centered care to this cohort of veterans. Results may also inform future
      work aimed at meeting the needs of both OEF/OIF veterans and MH providers.

PMID- 24668063
TI  - Effect of an essential oil mixture on skin reactions in women undergoing
      radiotherapy for breast cancer: a pilot study.
AB  - PURPOSE: This pilot study compared the effects of an essential oil mixture versus
      standard care on skin reactions in breast cancer patients receiving radiation.
      METHOD: Using an experimental design, 24 patients were randomized to standard
      care (i.e., RadiaPlexRxTM ointment) or an essential oil mixture. Products were
      applied topically three times a day until 1 month postradiation. Weekly skin
      assessments were recorded and women completed patient satisfaction and quality of
      life (QOL) instruments at 3-, 6-, and 10-week intervals. RESULTS: No significant
      differences were found for skin, QOL, or patient satisfaction at interim or
      follow-up time points. Effect sizes were as follows: skin = .01 to .07 (small
      medium effect); QOL = .01 to .04 (small effect); patient satisfaction = .02
      (small effect). CONCLUSION: The essential oil mixture did not provide a better
      skin protectant effect than standard care. These findings suggest the essential
      oil mixture is equivalent to RadiaPlexRx, a common product used as standard care
      since it has been shown to be effective in protecting skin from radiation. Thus,
      this pilot provides evidence to support botanical or nonpharmaceutical options
      for women during radiotherapy for breast cancer.

PMID- 24668064
TI  - Spirituality and nursing: an Ismaili perspective on holistic nursing care.
AB  - This article seeks to describe a professional, personal, and cultural
      understanding of spirituality in nursing care. It revisits and refines the many
      concept clarifications of spirituality in our practice discipline, while
      reflecting on the potential meanings and learnings from Ismaili tenets and
      principles within a personal nursing practice. Through a review of mainstream
      literature in conjunction with nontraditional literature, the implicit is made
      explicit in terms of similarities and differences, as well as opportunities for
      further exploration. The summary brings forward the persistent gaps and questions
      on critical areas such as creating the "place" and "operationalizing" of
      spirituality. These continue to challenge and intrigue nurses seeking spiritual
      comfort for both themselves and their clients. 

PMID- 24668065
TI  - From acetone metalation to the catalytic alpha-arylation of acyclic ketones with
      NHC-nickel(II) complexes.
AB  - Air-stable N-heterocyclic carbene-nickel(ii) complexes at concentrations as low
      as 1 mol% exhibit high catalytic activity for the alpha-arylation of acyclic
      ketones and join a highly restricted list of nickel catalysts for this key
      reaction. Mechanistic investigations suggest a radical pathway. 

PMID- 24668066
TI  - Highly efficient N-glycoproteomic sample preparation by combining C(18) and
      graphitized carbon adsorbents.
AB  - Conventional N-glycoproteome analysis usually applies C18 reversed-phase (RP)
      adsorbent for sample purification, which will lead to unavoidable sample loss due
      to the high hydrophilicity of N-glycopeptides. In this study, a porous
      graphitized carbon (PGC) absorbent was combined with a C18 adsorbent for N
      glycopeptide purification in comprehensive N-glycoproteome analysis based on the
      hydrophobic and polar interactions between carbon and N-glycans. It was observed
      that the small hydrophilic N-glycopeptides that cannot retain onto C18 adsorbent
      can be captured by the graphitized carbon, while the large hydrophobic N
      glycopeptides that cannot retain onto the graphitized carbon can be feasibly
      captured by the C18 adsorbent. Comparing with sample purification by using C18
      adsorbent only, 28.5 % more N-glycopeptides were identified by combining both C18
      and PGC adsorbents. The C18-PGC strategy was further applied for both sample
      purification and pre-fractionation of a complex protein sample from HeLa cell.
      After hydrophilic interaction chromatography enrichment, 1,484 unique N
      glycopeptides with 1,759 unique N-glycosylation sites were finally identified.

PMID- 24668067
TI  - Application of capillary electrophoresis for the early diagnosis of cancer.
AB  - Early diagnosis is the key to the effective treatment of cancer. The detection of
      cancer biomarkers plays a critical role not only in cancer early diagnosis, but
      also in classification and staging tumor progression, or assessment prognosis and
      treatment response. Currently, various molecular diagnostic techniques have been
      developed for cancer biomarker studies, with many of the more effective
      approaches requiring a separation step before detection. Capillary
      electrophoresis (CE) can perform rapid and efficient separation with small
      samples, which is well-suited for analysis of both small- and macro- molecule
      biomarkers in complex samples. CE has different separation modes and can couple
      to different detectors into a variety of platforms, such as conducting studies on
      DNA/ RNA point mutation, protein misexpression, and metabolite abnormality.
      Similarly, microchip capillary electrophoresis (MCE) appears as a very important
      biomarker screening platform with the merits of high throughput, integration, and
      miniaturization, which makes it a promising clinical tool. By hyphenated
      different detectors, or integrated with immunoassay, PCR/LDR and related
      technologies, MCE can be constructed into diverse platforms used in genomics,
      proteomics, and metabolomics study for biomarkers discovery. The multiplex
      biomarker screening approach via CE- or MCE-based platforms is becoming a trend.
      This paper focuses on studies of cancer biomarkers via CE/MCE platforms, based on
      the studies published over the past 3 years. Some recent CE applications in the
      field of cancer study, such as cancer theranostics, are introduced.

PMID- 24668068
TI  - The role of working memory in inferential sentence comprehension.
AB  - Existing literature on inference making is large and varied. Trabasso and
      Magliano (Discourse Process 21(3):255-287, 1996) proposed the existence of three
      types of inferences: explicative, associative and predictive. In addition, the
      authors suggested that these inferences were related to working memory (WM). In
      the present experiment, we investigated whether WM capacity plays a role in our
      ability to answer comprehension sentences that require text information based on
      these types of inferences. Participants with high and low WM span read two
      narratives with four paragraphs each. After each paragraph was read, they were
      presented with four true/false comprehension sentences. One required verbatim
      information and the other three implied explicative, associative and predictive
      inferential information. Results demonstrated that only the explicative and
      predictive comprehension sentences required WM: participants with high verbal WM
      were more accurate in giving explanations and also faster at making predictions
      relative to participants with low verbal WM span; in contrast, no WM differences
      were found in the associative comprehension sentences. These results are
      interpreted in terms of the causal nature underlying these types of inferences.

PMID- 24668069
TI  - Evaluating N-benzylgalactonoamidines as putative transition state analogs for
      beta-galactoside hydrolysis.
AB  - Experimental evidence is provided for p-methylbenzyl-D-galactonoamidine to
      function as a true transition state analog for the enzymatic hydrolysis of aryl
      beta-D-galactopyranosides by beta-galactosidase (A. oryzae). The compound
      exhibits inhibition constants in the low nanomolar concentration range (12-56 nM)
      for a selection of substrates. Along these lines, a streamlined synthetic method
      based on phase-transfer catalysis was optimized to afford the required variety of
      new aryl-beta-D-galactopyranosides. Last, the stability of the galactonoamidines
      under the assay conditions was confirmed.

PMID- 24668070
TI  - Efficiency maximization in solar-thermochemical fuel production: challenging the
      concept of isothermal water splitting.
AB  - Widespread adoption of solar-thermochemical fuel production depends on its
      economic viability, largely driven by the efficiency of use of the available
      solar resource. Herein, we analyze the efficiency of two-step cycles for
      thermochemical hydrogen production, with emphasis on efficiency. Owing to water
      thermodynamics, isothermal H2 production is shown to be impractical and
      inefficient, irrespective of reactor design or reactive oxide properties, but an
      optimal temperature difference between cycle steps, for which efficiency is the
      highest, can be determined for a wide range of other operating parameters. A
      combination of well-targeted pressure and temperature swing, rather than either
      individually, emerges as the most efficient mode of operation of a two-step
      thermochemical cycle for solar fuel production. 

PMID- 24668071
TI  - Letter to the editor: External rotation immobilization for primary shoulder
      dislocation: a randomized controlled trial.

PMID- 24668072
TI  - Orthopaedic education in the United Kingdom.

PMID- 24668073
TI  - Are there biological markers for wear or corrosion? A systematic review.
AB  - BACKGROUND: Identification of biomarkers associated with wear and tribocorrosion
      in joint arthroplasty would be helpful to enhance early detection of aseptic
      loosening and/or osteolysis and to improve understanding of disease progression.
      There have been several new reports since the last systematic review (which
      covered research through mid-2008) justifying a new assessment.
      QUESTIONS/PURPOSES: We sought to determine which biomarkers have the most promise
      for early diagnosis and monitoring of aseptic loosening and/or osteolysis related
      to wear or corrosion in total joint arthroplasty. METHODS: We performed a
      systematic review using MEDLINE and EMBASE databases, covering the period through
      December 2013, and identified 1050 articles. We restricted the definition of
      biomarker to biomolecules and imaging parameters useful for diagnosis and
      monitoring of disease progression, only including articles in English. We chose
      65 articles for full review, including 44 from the original search and 21 from
      subsequent hand searches. We used the 22 articles in which patients with total
      joint arthroplasty who had aseptic loosening and/or periimplant osteolysis
      unrelated to sepsis had been compared with patients with total joint arthroplasty
      with stable implants. There were 90 comparisons of these two patient populations
      involving 35 different biomarkers. RESULTS: Diagnostic accuracy was assessed in
      nine of the 90 comparisons with the highest accuracy found for tartrate-resistant
      acid phosphatase 5b (0.96), although a separate comparison for this biomarker
      found a lower accuracy (0.76). Accuracy of > 0.80 was also found for crosslinked
      n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The
      most studied markers, tumor necrosis factor-alpha and interleukin-1beta, were
      found to differ in the affected and control groups in < 30% of the comparisons.
      Thirty of the 35 biomarkers were studied in four or fewer separate comparisons
      with nearly half of the biomarkers (17) studied in only one comparison. Many of
      the comparisons were not able to eliminate a number of confounding variables, and
      there was only one prospective study. CONCLUSIONS: Currently, there are no
      validated biomarkers for early diagnosis and monitoring of the biological
      sequelae of wear or tribocorrosion, although there are some promising leads,
      including markers of bone turnover.

PMID- 24668074
TI  - CORR Insights(r): Hospital for special surgery pediatric functional activity
      brief scale predicts physical fitness testing performance.

PMID- 24668075
TI  - CORR Insights(r): Rotating-platform TKA no different from fixed-bearing TKA
      regarding survivorship or performance: a meta-analysis.

PMID- 24668076
TI  - Pure red cell aplasia complicating the course of long-standing mantle cell
      lymphoma.
AB  - Pure red cell aplasia (PRCA) is a rare cause of severe hypoplastic anemia
      characterized by profound depletion of erythroid precursors. Although PRCA may be
      associated with lymphoproliferative diseases, it has never been described in
      mantle cell lymphoma (MCL). We report what to our knowledge is the first case of
      a patient with indolent, non-nodal MCL complicated by PRCA. The patient presented
      with severe hypoproliferative anemia in the setting of a long-standing diagnosis
      of B-cell chronic lymphocytic leukemia. Bone marrow studies revealed the complete
      absence of erythroid progenitors. Cyclin D1 positivity on immunohistochemistry,
      confirmed by a positive FISH for t(11;14) (q13;q32), established the final
      diagnosis of MCL in conjunction with PRCA. Rituximab monotherapy led to rapid
      remission of splenomegaly and the leukemic picture, but the patient achieved
      transfusion independency only with subsequent administration of cyclosporine-A,
      and remained so during the subsequent 15 months despite the gradual disease
      recurrence.

PMID- 24668077
TI  - Intervention assessments in the control of PM10 emissions from an urban waste
      transfer station.
AB  - While vehicle emissions present the most widespread cause of breaches of EU air
      quality standards in urban areas of the UK, the greatest PM10 concentrations are
      often recorded close to small industrial sites with significant and long-term
      public exposure within close proximity. This is particularly the case in London,
      where monitoring in densely populated locations, adjacent to waste transfer
      stations (WTS), routinely report the highest PM10 concentrations in the city.
      This study aims to assess the impact of dust abatement measures taken at a WTS in
      west London and, in so doing, develop analysis techniques transferrable to other
      similar industrial situations. The study was performed in a 'blinded fashion',
      i.e., no details of operating times, activities or remediation measures were
      provided prior to the analysis. The study established that PM10 concentrations
      were strongly related to the industrial area's working hours and atmospheric
      humidity. The primary source of local particulate matter during working hours was
      found to be from the industrial area itself, not from the adjacent road serving
      the site. CUSUM analysis revealed a strong, sustained change point coinciding
      with a number of modifications at the WTS. Analysis suggested that introducing a
      vehicle washer bay, leading to a less dry and dusty yard, and ceasing stock
      piling and waste handling activities outside of the open shed had the greatest
      effect on PM10 concentrations. The techniques developed in this study should
      empower licensing authorities to more effectively characterise and mitigate
      particulate matter generated by urban industrial activities, thereby improving
      the health and quality of life of the local population. 

PMID- 24668079
TI  - Buckling dynamics of a solvent-stimulated stretched elastomeric sheet.
AB  - When stretched uniaxially, a thin elastic sheet may exhibit buckling. The
      occurrence of buckling depends on the geometrical properties of the sheet and the
      magnitude of the applied strain. Here we show that an elastomeric sheet initially
      stable under uniaxial stretching can destabilize when exposed to a solvent that
      swells the elastomer. We demonstrate experimentally and computationally that the
      features of the buckling pattern depend on the magnitude of stretching, and this
      observation offers a new way for controlling the shape of a swollen homogeneous
      thin sheet. 

PMID- 24668078
TI  - Modeling the dynamics of backyard chicken flows in traditional trade networks in
      Thailand: implications for surveillance and control of avian influenza.
AB  - In Southeast Asia, traditional poultry marketing chains have been threatened by
      epidemics caused by the highly pathogenic avian influenza H5N1 (HPAI H5N1) virus.
      In Thailand, the trade of live backyard chickens is based on the activities of
      traders buying chickens from villages and supplying urban markets with chicken
      meat. This study aims to quantify the flows of chickens traded during a 1-year
      period in a province of Thailand. A compartmental stochastic dynamic model was
      constructed to illustrate trade flows of live chickens from villages to
      slaughterhouses. Live poultry movements present important temporal variations
      with increased activities during the 15 days preceding the Chinese New Year and,
      to a lesser extent, other festivals (Qingming Festival, Thai New Year, Hungry
      Ghost Festival, and International New Year). The average distance of poultry
      movements ranges from 4 to 25 km, defining a spatial scale for the risk of avian
      influenza that spread through traditional poultry marketing chains. Some
      characteristics of traditional poultry networks in Thailand, such as overlapping
      chicken supply zones, may facilitate disease diffusion over longer distances
      through combined expansion and relocation processes. This information may be of
      use in tailoring avian influenza and other emerging infectious poultry disease
      surveillance and control programs provided that the cost-effectiveness of such
      scenarios is also evaluated in further studies. 

PMID- 24668082
TI  - Cobalt: Yvonne McKague Housser.

PMID- 24668083
TI  - Groups aim for trustworthy clinical practice guidelines.

PMID- 24668084
TI  - Estimate of new chronic HCV cases lower than expected.

PMID- 24668085
TI  - World leaders push to prepare for global threats.

PMID- 24668097
TI  - Clinical practice guidelines for chronic cardiovascular disorders: a roadmap for
      the future.

PMID- 24668098
TI  - Fulfilling the promise of "anyone, anywhere" to perform CPR.

PMID- 24668099
TI  - A piece of my mind. Slippery slopes and landing on your feet.

PMID- 24668100
TI  - Radiofrequency ablation for Barrett esophagus with confirmed low-grade dysplasia.

PMID- 24668101
TI  - Electronic alcohol screening and brief interventions: expectations and reality.

PMID- 24668102
TI  - Radiofrequency ablation vs endoscopic surveillance for patients with Barrett
      esophagus and low-grade dysplasia: a randomized clinical trial.
AB  - IMPORTANCE: Barrett esophagus containing low-grade dysplasia is associated with
      an increased risk of developing esophageal adenocarcinoma, a cancer with a
      rapidly increasing incidence in the western world. OBJECTIVE: To investigate
      whether endoscopic radiofrequency ablation could decrease the rate of neoplastic
      progression. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical
      trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus
      containing low-grade dysplasia at 9 European sites between June 2007 and June
      2011. Patient follow-up ended May 2013. INTERVENTIONS: Eligible patients were
      randomly assigned in a 1:1 ratio to either endoscopic treatment with
      radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation
      was performed with the balloon device for circumferential ablation of the
      esophagus or the focal device for targeted ablation, with a maximum of 5 sessions
      allowed. MAIN OUTCOMES AND MEASURES: The primary outcome was neoplastic
      progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up
      since randomization. Secondary outcomes were complete eradication of dysplasia
      and intestinal metaplasia and adverse events. RESULTS: Sixty-eight patients were
      randomized to receive ablation and 68 to receive control. Ablation reduced the
      risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for
      ablation vs 26.5% for control; 95% CI, 14.1%-35.9%; P < .001) and the risk of
      progression to adenocarcinoma by 7.4% (1.5% for ablation vs 8.8% for control; 95%
      CI, 0%-14.7%; P = .03). Among patients in the ablation group, complete
      eradication occurred in 92.6% for dysplasia and 88.2% for intestinal metaplasia
      compared with 27.9% for dysplasia and 0.0% for intestinal metaplasia among
      patients in the control group (P < .001). Treatment-related adverse events
      occurred in 19.1% of patients receiving ablation (P < .001). The most common
      adverse event was stricture, occurring in 8 patients receiving ablation (11.8%),
      all resolved by endoscopic dilation (median, 1 session). The data and safety
      monitoring board recommended early termination of the trial due to superiority of
      ablation for the primary outcome and the potential for patient safety issues if
      the trial continued. CONCLUSIONS AND RELEVANCE: In this randomized trial of
      patients with Barrett esophagus and a confirmed diagnosis of low-grade dysplasia,
      radiofrequency ablation resulted in a reduced risk of neoplastic progression over
      3 years of follow-up. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1198.

PMID- 24668103
TI  - Web-based alcohol screening and brief intervention for university students: a
      randomized trial.
AB  - IMPORTANCE: Unhealthy alcohol use is a leading contributor to the global burden
      of disease, particularly among young people. Systematic reviews suggest efficacy
      of web-based alcohol screening and brief intervention and call for effectiveness
      trials in settings where it could be sustainably delivered. OBJECTIVE: To
      evaluate a national web-based alcohol screening and brief intervention program.
      DESIGN, SETTING, AND PARTICIPANTS: A multisite, double-blind, parallel-group,
      individually randomized trial was conducted at 7 New Zealand universities. In
      April and May of 2010, invitations containing hyperlinks to the Alcohol Use
      Disorders Identification Test-Consumption (AUDIT-C) screening test were e-mailed
      to 14,991 students aged 17 to 24 years. INTERVENTIONS: Participants who screened
      positive (AUDIT-C score >=4) were randomized to undergo screening alone or to 10
      minutes of assessment and feedback (including comparisons with medical guidelines
      and peer norms) on alcohol expenditure, peak blood alcohol concentration, alcohol
      dependence, and access to help and information. MAIN OUTCOMES AND MEASURES: A
      fully automated 5-month follow-up assessment was conducted that measured 6
      primary outcomes: consumption per typical occasion, drinking frequency, volume of
      alcohol consumed, an academic problems score, and whether participants exceeded
      medical guidelines for acute harm (binge drinking) and chronic harm (heavy
      drinking). A Bonferroni-corrected significance threshold of .0083 was used to
      account for the 6 comparisons and a sensitivity analysis was used to assess
      possible attrition bias. RESULTS: Of 5135 students screened, 3422 scored 4 or
      greater and were randomized, and 83% were followed up. There was a significant
      effect on 1 of the 6 prespecified outcomes. Relative to control participants,
      those who received intervention consumed less alcohol per typical drinking
      occasion (median 4 drinks [interquartile range {IQR}, 2-8] vs 5 drinks [IQR 2-8];
      rate ratio [RR], 0.93 [99.17% CI, 0.86-1.00]; P = .005) but not less often (RR,
      0.95 [99.17% CI, 0.88-1.03]; P = .08) or less overall (RR, 0.95 [99.17% CI, 0.81
      1.10]; P = .33). Academic problem scores were not lower (RR, 0.91 [99.17% CI,
      0.76-1.08]; P = .14) and effects on the risks of binge drinking (odds ratio [OR],
      0.84 [99.17% CI, 0.67-1.05]; P = .04) and heavy drinking (OR, 0.77 [99.17% CI,
      0.56-1.05]; P = .03) were not significantly significant. In a sensitivity
      analysis accounting for attrition, the effect on alcohol per typical drinking
      occasion was no longer statistically significant. CONCLUSIONS AND RELEVANCE: A
      national web-based alcohol screening and brief intervention program produced no
      significant reductions in the frequency or overall volume of drinking or academic
      problems. There remains a possibility of a small reduction in the amount of
      alcohol consumed per typical drinking occasion. TRIAL REGISTRATION: anzctr.org.au
      Identifier: ACTRN12610000279022.

PMID- 24668107
TI  - Rethinking warfarin for atrial fibrillation.

PMID- 24668106
TI  - Outcomes of carotid endarterectomy and stenting in elderly patients.

PMID- 24668105
TI  - Association of distance from a transplant center with access to waitlist
      placement, receipt of liver transplantation, and survival among US veterans.
AB  - IMPORTANCE: Centralization of specialized health care services such as organ
      transplantation and bariatric surgery is advocated to improve quality, increase
      efficiency, and reduce cost. The effect of increased travel on access and
      outcomes from these services is not fully understood. OBJECTIVE: To evaluate the
      association between distance from a Veterans Affairs (VA) transplant center
      (VATC) and access to being waitlisted for liver transplantation, actually having
      a liver transplant, and mortality. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective study of veterans meeting liver transplantation eligibility
      criteria from January 1, 2003, until December 31, 2010, using data from the
      Veterans Health Administration's integrated, national, electronic medical record
      linked to Organ Procurement and Transplantation Network data. MAIN OUTCOMES AND
      MEASURES: The primary outcome was being waitlisted for transplantation at a VATC.
      Secondary outcomes included being waitlisted at any transplant center, undergoing
      a transplantation, and survival. RESULTS: From 2003-2010, 50,637 veterans were
      classified as potentially eligible for transplant; 2895 (6%) were waitlisted and
      1418 of those were waitlisted (49%) at 1 of the 5 VATCs. Of 3417 veterans
      receiving care at a VA hospital located within 100 miles from a VATC, 244 (7.1%)
      were waitlisted at a VATC and 372 (10.9%) at any transplant center (VATC and non
      VATCs). Of 47,219 veterans receiving care at a VA hospital located more than 100
      miles from a VATC, 1174 (2.5%) were waitlisted at a VATC and 2523 (5.3%) at any
      transplant center (VATC and non-VATCs). In multivariable models, increasing
      distance to closest VATC was associated with significantly lower odds of being
      waitlisted at a VATC (odds ratio [OR], 0.91 [95% CI, 0.89-0.93] for each doubling
      in distance) or any transplant center (OR, 0.94 [95% CI, 0.92-0.96] for each
      doubling in distance). For example, a veteran living 25 miles from a VATC would
      have a 7.4% (95% CI, 6.6%-8.1%) adjusted probability of being waitlisted, whereas
      a veteran 100 miles from a VATC would have a 6.2% (95% CI, 5.7%-6.6%) adjusted
      probability. In adjusted models, increasing distance from a VATC was associated
      with significantly lower transplantation rates (subhazard ratio, 0.97; 95% CI,
      0.95-0.98 for each doubling in distance). There was significantly increased
      mortality among waitlisted veterans from the time of first hepatic decompensation
      event in multivariable survival models (hazard ratio, 1.03; 95% CI, 1.01-1.04 for
      each doubling in distance). For example, a waitlisted veteran living 25 miles
      from a VATC would have a 62.9% (95% CI, 59.1%-66.1%) 5-year adjusted probability
      of survival from first hepatic decompensation event compared with a 59.8% (95%
      CI, 56.3%-63.1%) 5-year adjusted probability of survival for a veteran living 100
      miles from a VATC. CONCLUSIONS AND RELEVANCE: Among VA patients meeting
      eligibility criteria for liver transplantation, greater distance from a VATC or
      any transplant center was associated with lower likelihood of being waitlisted,
      receiving a liver transplant, and greater likelihood of death. The relationship
      between these findings and centralizing specialized care deserves further
      investigation.

PMID- 24668108
TI  - Population trends from 2000-2011 in nuclear myocardial perfusion imaging use.

PMID- 24668109
TI  - Antithrombotic therapy after transcatheter aortic valve replacement.

PMID- 24668110
TI  - Antithrombotic therapy after transcatheter aortic valve replacement--reply.

PMID- 24668111
TI  - Use of placebo in a trial of thalidomide for pediatric Crohn disease.

PMID- 24668112
TI  - Use of placebo in a trial of thalidomide for pediatric Crohn disease--reply.

PMID- 24668113
TI  - Declaration of Helsinki and protection for vulnerable research participants.

PMID- 24668104
TI  - Glycated hemoglobin measurement and prediction of cardiovascular disease.
AB  - IMPORTANCE: The value of measuring levels of glycated hemoglobin (HbA1c) for the
      prediction of first cardiovascular events is uncertain. OBJECTIVE: To determine
      whether adding information on HbA1c values to conventional cardiovascular risk
      factors is associated with improvement in prediction of cardiovascular disease
      (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual-participant
      data available from 73 prospective studies involving 294,998 participants without
      a known history of diabetes mellitus or CVD at the baseline assessment. MAIN
      OUTCOMES AND MEASURES: Measures of risk discrimination for CVD outcomes (eg, C
      index) and reclassification (eg, net reclassification improvement) of
      participants across predicted 10-year risk categories of low (<5%), intermediate
      (5% to <7.5%), and high (>= 7.5%) risk. RESULTS: During a median follow-up of 9.9
      (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD
      outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded.
      In analyses adjusted for several conventional cardiovascular risk factors, there
      was an approximately J-shaped association between HbA1c values and CVD risk. The
      association between HbA1c values and CVD risk changed only slightly after
      adjustment for total cholesterol and triglyceride concentrations or estimated
      glomerular filtration rate, but this association attenuated somewhat after
      adjustment for concentrations of high-density lipoprotein cholesterol and C
      reactive protein. The C-index for a CVD risk prediction model containing
      conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to
      0.7517). The addition of information on HbA1c was associated with a C-index
      change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of
      0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The
      improvement provided by HbA1c assessment in prediction of CVD risk was equal to
      or better than estimated improvements for measurement of fasting, random, or
      postload plasma glucose levels. CONCLUSIONS AND RELEVANCE: In a study of
      individuals without known CVD or diabetes, additional assessment of HbA1c values
      in the context of CVD risk assessment provided little incremental benefit for
      prediction of CVD risk.

PMID- 24668114
TI  - Declaration of Helsinki and protection for vulnerable research participants-
      reply.

PMID- 24668116
TI  - Cardiac disturbances as the result of exhaustion.

PMID- 24668117
TI  - JAMA patient page. Salt in the diet.

PMID- 24668118
TI  - Altered white matter microstructural connectivity in cluster headaches: a
      longitudinal diffusion tensor imaging study.
AB  - BACKGROUND: Functional and structural disruptions to the pain matrix, which may
      involve changes in white matter (WM) pathways connecting the pain-processing
      system and hypothalamus, have been implicated in the pathophysiology of cluster
      headache (CH). However, previous studies have obtained inconclusive results
      regarding WM changes in CH, and WM variations between "in-bout" and "out-of-bout"
      periods of CH remain to be determined. METHODS: Multiple diffusivity indices
      obtained by diffusion tensor imaging (DTI) and post-hoc probabilistic
      tractography were used to elucidate CH pathophysiology. RESULTS: Compared to
      healthy participants, in-bout CH patients showed regionally higher absolute
      (radial and mean) diffusivities in the left medial frontal gyrus and frontal sub
      gyrus and lower absolute (axial, radial and mean) diffusivities in the right
      parahippocampal gyrus of the limbic lobe. These changes during the in-bout period
      generally persisted in the out-of-bout period, except for the left cerebellar
      tonsil. Post-hoc probabilistic tractography showed highly consistent anatomical
      connections between these altered areas and the hypothalamus across participants.
      CONCLUSIONS: Distinct WM changes were observed in episodic CH. Connections
      between the pain-modulation areas and hypothalamus may be involved in CH
      pathophysiology.

PMID- 24668121
TI  - Composite porous membranes with an ultrathin selective layer for vanadium flow
      batteries.
AB  - An ultrathin Nafion film was introduced onto the poly(ether sulfone) (PES)
      sulfonated poly(ether ether ketone) (SPEEK) porous membranes for vanadium flow
      battery (VFB) application. The composite membranes showed very high ion
      selectivity, good stability and excellent performance (energy efficiency 86.5% at
      80 mA cm(-2)) in VFB. 

PMID- 24668120
TI  - Clinically high-risk prostate cancer patients comprise a relevant number of
      cancers with overall favorable tumor characteristics.
AB  - PURPOSE: We hypothesized that a relevant number of patients with clinically high
      risk prostate cancer (PCA) indeed harbor overall favorable tumor characteristics
      (OFTC) (i.e., pT2a-c and Gleason score <=3 + 4 = 7 and pN0/X) and that in these
      patients radical prostatectomy (RP) alone is most likely curative. METHODS:
      Between June 1, 1997, and October 31, 2011, 2,346 patients with biopsy-detected
      PCA underwent RP. According to D'Amico, 1,767 patients presented low
      /intermediate-risk PCA, and 579 presented high-risk PCA. We compared the
      incidence of OFTC between low-/intermediate-risk and high-risk patients, and
      between high-risk patients with different risk factor constellations.
      Furthermore, overall survival (OS), cancer-specific survival (CSS) and
      biochemical progression-free survival (BFS) were calculated for low-/intermediate
      risk and high-risk patients with and without OFTC. RESULTS: High-risk patients
      were less likely to harbor OFTC (17.3 vs. 58.2 %; p < 0.001). That means,
      however, that nearly one in five patients with clinically high-risk PCA indeed
      had OFTC. Particularly, the subgroup with PSA >20 ng/ml or cT2c-3 tumor as sole
      high-risk factor showed a considerable proportion of OFTC in 30.2 and 26.1 % of
      cases, respectively. While the entire high-risk group had shorter OS, CSS and BFS
      than the low-/intermediate-risk group, high-risk patients with OFTC had
      comparably good OS, CSS and BFS as low-/intermediate-risk patients with OFTC.
      CONCLUSIONS: Nearly, one in five patients assumed to have high-risk PCA indeed
      had OFTC. Particularly, patients with PSA >20 ng/ml or cT2c-3 tumor as sole high
      risk factor were often misclassified. However, these misclassified patients
      achieve excellent survival and have a reasonable chance of cure with RP alone.

PMID- 24668119
TI  - Safe-R: a novel score, accounting for oncological safe nerve-sparing at radical
      prostatectomy for localized prostate cancer.
AB  - OBJECTIVES: The objectives of the study were to describe a novel score (safe-R),
      combining information on surgical margin status (SM) and extend of nerve-sparing
      (NS) applicable for all patients undergoing radical prostatectomy (RP), and to
      test the impact of our frozen-section navigated nerve-sparing approach
      (NeuroSAFE) on safe-R score. METHODS: We retrospectively analyzed 9,635 RPs
      performed at our center between 2002 and 2011. Of these, 47 % were conducted with
      NeuroSAFE. Proportions of NS and SM status were assessed. Subsequently, a score
      for oncological safe NS (safe-R) was developed; Safe-R was categorized as 3 (for
      negative SM and bilateral NS), 2 (for negative SM and unilateral NS), 1 (for
      negative SM without NS), and 0 (for patients with positive SM), respectively. The
      impact of NeuroSAFE on safe-R was analyzed by chi-square test and confirmed by
      multinomial logistic regression, adjusting for preoperative risk factors.
      RESULTS: Applying NeuroSAFE resulted in enhanced safe-R score, indicating lower
      rates of positive SM and higher rates of NS, across all risk categories (all p <
      0.001). For example in high-risk patients, NeuroSAFE resulted in lower
      proportions of safe-R 0 (27.6 vs. 33.6 %) and higher proportions of safe-R 3
      (32.4 vs. 17.1 %, p < 0.001). Linkage between the NeuroSAFE approach and safe-R
      was confirmed after multinomial logistic adjustment for preoperative risk
      factors. All results were confirmed in a propensity-matched cohort (matched for
      preoperative risk factors and year of surgery, data not shown). CONCLUSION: Safe
      R represents a novel tool to assess and report on oncological safe nerve-sparing
      in RP. NeuroSAFE is associated with enhanced safe-R scores.

PMID- 24668122
TI  - Environmental monitoring of Micro Prespa Lake basin (Western Macedonia, Greece):
      hydrogeochemical characteristics of water resources and quality trends.
AB  - The Micro Prespa basin is a trilateral catchment area of significant importance
      with a unique ecosystem closely related to the homonymous lake. In this frame, a
      fully operational monitoring project was carried out including continuous real
      time measurements in Micro Prespa Lake with the use of a multi-sensor probe, as
      well as periodical sampling and analyses of all available water systems for an
      extended set of 85 parameters. Four main interacting water systems were
      identified, including alluvial and karstic aquifers, Micro Prespa Lake and
      adjacent drainage network. The results outlined that general environmental
      conditions are satisfying in respect to the relative legislation and the
      hydrogeochemical signatures. However, trends of environmental pressures were
      ascertained as a result of natural (geogenic) factors, embracing seasonal peaks
      for Ni, Pb, and NH4 mainly in groundwater systems. Based on chlorophyll a
      records, Micro Prespa is classified as oligotrophic to slightly mesotrophic,
      subjected to seasonal variations. Heavy metal concentrations are low, except Ni
      which appears to have elevated values during the dry hydrological period.
      Finally, the hydrogeochemistry of drainage network is primarily influenced by
      surface runoff of the surrounding mountainous areas, hence elevated phosphorus
      values of the Aghios Germanos stream are possibly linked with the leaching of the
      granitic formations on the east. 

PMID- 24668124
TI  - Self-healing catalysts: Co(3)O(4) nanorods for Fischer-Tropsch synthesis.
AB  - We combine kinetic and spectroscopic data to demonstrate the concept of a self
      healing catalyst, which effectively eliminates the need for catalyst
      regeneration. The observed self-healing is triggered by controlling the
      crystallographic orientation at the catalyst surface. 

PMID- 24668123
TI  - Black carbon concentrations in a goods-movement neighborhood of Philadelphia, PA.
AB  - Communities along the Delaware River in Philadelphia, USA such as Port Richmond,
      are subject to traffic associated with goods movement to and from port facilities
      and local industry. Air pollution associated with this traffic poses an
      environmental health concern in this and other urban areas. Our study measures
      black carbon (BC) in Port Richmond and examines its relationship to expected
      sources such as truck traffic. We used a participatory sampling method to conduct
      1-min measurements over 8-hour periods at 14 homes, a school and park, during a 4
      week period in June 2012. Measurements over 9 sampling days had a 30-min average
      BC concentration of 1.2 MUg m(-3), and a maximum of 12 MUg m(-3). Statistical
      analyses showed some effect of traffic, but greater association between BC
      concentrations and weather and time of day. BC concentrations varied more by
      location than by day, and distance to traffic arterials and interstate freeway
      was a predictor of this variance. While our dataset is limited by number and
      variety of observations, major findings indicate that BC concentration varies
      more by location than by day, there is a decrease in median BC concentration with
      increased distance from an interstate highway, and an expected effect of diesel
      traffic on average daily BC concentrations. Our findings are an important step
      towards understanding patterns and determinants of BC concentration in
      communities colocated with major ports. Our study also demonstrates that
      participatory methods in air pollution monitoring can help increase awareness of
      local air pollution levels. 

PMID- 24668126
TI  - Monto Ho, in memoriam.

PMID- 24668125
TI  - Molecular diagnosis of central nervous system opportunistic infections in HIV
      infected Zambian adults.
AB  - BACKGROUND: Knowledge of central nervous system (CNS) opportunistic infections
      (OIs) among people living with human immunodeficiency virus (HIV) in sub-Saharan
      Africa is limited. METHODS: We analyzed 1 cerebrospinal fluid (CSF) sample from
      each of 331 HIV-infected adults with symptoms suggestive of CNS OI at a tertiary
      care center in Zambia. We used pathogen-specific primers to detect DNA from JC
      virus (JCV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr
      virus (EBV), herpes simplex virus (HSV) types 1 and 2, Mycobacterium
      tuberculosis, and Toxoplasma gondii via real-time polymerase chain reaction
      (PCR). RESULTS: The patients' median CD4(+) T-cell count was 89 cells/uL
      (interquartile range, 38-191 cells/uL). Of 331 CSF samples, 189 (57.1%) had at
      least 1 pathogen. PCR detected DNA from EBV in 91 (27.5%) patients, M.
      tuberculosis in 48 (14.5%), JCV in 20 (6.0%), CMV in 20 (6.0%), VZV in 13 (3.9%),
      HSV-1 in 5 (1.5%), and HSV-2 and T. gondii in none. Fungal and bacteriological
      studies showed Cryptococcus in 64 (19.5%) patients, pneumococcus in 8 (2.4%), and
      meningococcus in 2 (0.6%). Multiple pathogens were found in 68 of 189 (36.0%)
      samples. One hundred seventeen of 331 (35.3%) inpatients died during their
      hospitalization. Men were older than women (median, 37 vs 34 years; P = .01),
      more recently diagnosed with HIV (median, 30 vs 63 days; P = .03), and tended to
      have a higher mortality rate (40.2% vs 30.2%; P = .07). CONCLUSIONS: CNS OIs are
      frequent, potentially treatable complications of AIDS in Zambia. Multiple
      pathogens often coexist in CSF. EBV is the most prevalent CNS organism in
      isolation and in coinfection. Whether it is associated with CNS disease or a
      marker of inflammation requires further investigation. More comprehensive testing
      for CNS pathogens could improve treatment and patient outcomes in Zambia.

PMID- 24668128
TI  - Phases of intermediate filament composition in Bergmann glia following cerebellar
      injury in adult rat.
AB  - In contrast to other astroglial populations, Bergmann glia (BG) form a strictly
      arranged system where each cell contacts the pia, with an architecture and
      function resembling that of immature radial glia. As a consequence, a post-lesion
      glial reaction is expected to differ from that observed in other parts of the
      brain. The present study describes the characteristic phases of intermediate
      filament protein formation during the different stages of BG response following
      injury and compares them with reactive glial patterns of other brain areas and
      patterns of glial development. The progress of Bergmann glial repair shares
      similar features with glial development. Following injury, BG developed nestin
      immunopositivity; then, colocalization of nestin and GFAP was observed. Finally,
      exclusively GFAP-immunopositive BG were restituted, denser, and thicker than
      before. The changes of intermediate filament composition appeared at first at the
      proximal and distal ends of BG fibers, i.e., at the perikaryal "root" and in the
      pial endfeet. No astrocytic invasion was present in the molecular layer, nor any
      distinct rearrangement of BG. These results demonstrate the role of the resident
      glia in glial reactions and refer to the priority of gliomeningeal connections.

PMID- 24668127
TI  - Children's head movements and postural stability as a function of task.
AB  - Manual dexterity and postural control develop throughout childhood, leading to
      changes in the synergistic relationships between head, hand and posture. But the
      postural developments that support complex manual task performance (i.e. beyond
      pointing and grasping) have not been examined in depth. We report two experiments
      in which we recorded head and posture data whilst participants simultaneously
      performed a visuomotor task. In Experiment 1, we explored the extent to which
      postural stability is affected by concurrently performing a visual and manual
      task whilst standing (a visual vs. manual-tracking task) in four age groups: 5-6
      years (n = 8), 8-9 years (n = 10), 10-11 years (n = 7) and 19-21 years (n = 9).
      For visual tracking, the children's but not adult's postural movement increased
      relative to baseline with a larger effect for faster moving targets. In manual
      tracking, we found greater postural movement in children compared to adults.
      These data suggest predictive postural compensation mechanisms develop during
      childhood to improve stability whilst performing visuomotor tasks. Experiment 2
      examined the extent to which posture is influenced by manual activity in three
      age groups of children [5-6 years (n = 14), 7-8 years (n = 25), and 9-10 years (n
      = 24)] when they were seated, given that many important tasks (e.g. handwriting)
      are learned and performed whilst seated. We found that postural stability varied
      in a principled manner as a function of task demands. Children exhibited
      increased stability when tracing a complex shape (which required less predictive
      postural adjustment) and decreased stability in an aiming task (which required
      movements that were more likely to perturb posture). These experiments shed light
      on the task-dependant relationships that exist between postural control
      mechanisms and the development of specific types of manual control.

PMID- 24668129
TI  - Neural representation of muscle dynamics in voluntary movement control.
AB  - Several theories of motor control posit that the nervous system has access to a
      neural representation of muscle dynamics. Yet, this has not been tested
      experimentally. Should such a representation exist, it was hypothesized that
      subjects who learned to control a virtual limb using virtual muscles would
      improve performance faster and show greater generalization than those who learned
      with a less dynamically complex virtual force generator. Healthy adults practiced
      using their biceps brachii activity to move a myoelectrically controlled virtual
      limb from rest to a standard target position with maximum speed and accuracy.
      Throughout practice, generalization was assessed with untrained target trials and
      sensitivity to actuator dynamics was probed by unexpected actuator model
      switches. In a muscle model subject group (n = 10), the biceps electromyographic
      signal activated a virtual muscle that pulled on the virtual limb with a force
      governed by muscle dynamics, defined by a nonlinear force-length-velocity
      relation and series elastic stiffness. A force generator group (n = 10) performed
      the same task, but the actuation force was a linear function of the biceps
      activation signal. Both groups made significant errors with unexpected actuator
      dynamics switches, supporting task sensitivity to actuator dynamics. The muscle
      model group improved performance as fast as the force generator group and showed
      greater generalization in early practice, despite using an actuator with more
      complex dynamics. These results are consistent with a preexisting neural
      representation of muscle dynamics, which may have offset any learning challenges
      associated with the more dynamically complex virtual muscle model.

PMID- 24668130
TI  - Gabapentin's anti-nausea and anti-emetic effects: a review.
AB  - Gabapentin's main clinical use is in the treatment of neuropathic pain where its
      binding to neuronal alpha-2/delta subunits of voltage-gated calcium channels
      (VGCCs) is critical to its mechanism of action. Over the past 10 years, there
      have been several reports of gabapentin also having anti-nausea and anti-emetic
      effects in conditions including postoperative nausea and vomiting (PONV),
      chemotherapy-induced nausea and vomiting (CINV), and hyperemesis gravidarum (HG).
      In this report, a MEDLINE electronic search was performed, and relevant citations
      were reviewed and classified by level of evidence; a grade of recommendation was
      then assigned for gabapentin's use for each studied indication. Out of 33
      clinical trials reviewed, 12 assessed nausea and/or vomiting (N/V) associated
      with gabapentin therapy as primary outcome measures. These 12 studies provided a
      Grade A recommendation for gabapentin use in treating PONV, a Grade B
      recommendation for use in treating CINV, and a Grade C recommendation for use in
      treating HG. Further research is needed to confirm these initial promising
      results, which implicate the alpha-2/delta VGCC subunit as a novel therapeutic
      target in the treatment of several N/V-associated clinical conditions. 

PMID- 24668131
TI  - Two-point tactile discrimination ability is influenced by temporal features of
      stimulation.
AB  - Two-point discrimination threshold is commonly used for assessing tactile spatial
      resolution. Since the effect of temporal features of cutaneous test stimulation
      on spatial discrimination ability is not yet well known, we determined whether
      the ability to discriminate between two stimulus locations varies with the
      interstimulus interval (ISI) of sequentially presented tactile stimuli or the
      length of the stimulus train. Electrotactile stimuli were applied to one or two
      locations on the skin of the thenar eminence of the hand in healthy human
      subjects. Tactile discrimination ability was determined using methods based on
      the signal detection theory allowing the assessment of sensory performance,
      independent of the subject's response criterion. With stimulus pairs, the ability
      to discriminate spatial features of stimulation (one location vs. two stimulus
      locations 4 cm apart) was improved when the ISI was equal to or longer than that
      required for tactile temporal discrimination. With stimulus trains, the ability
      to discriminate spatial features of stimulation was significantly improved with
      an increase in the stimulus train (from 3 to 11 pulses corresponding to train
      lengths from 40 to 200 ms). These results indicate that temporal features of
      tactile stimulation significantly influence sensory performance in a tactile
      spatial discrimination task. Precise control of temporal stimulus parameters
      should help to reduce variations in results on the two-point discrimination
      threshold.

PMID- 24668132
TI  - Electroretinograms and level of aqueous vascular endothelial growth factor in
      eyes with hemicentral retinal vein occlusion or branch retinal vein occlusion.
AB  - PURPOSE: Hemicentral retinal vein occlusion (hCRVO) is a disease related to CRVO
      but not to branch retinal vein occlusion (BRVO). We reported a significant
      correlation between aqueous vascular endothelial growth factor (VEGF) levels and
      the implicit time of 30-Hz flicker electroretinogram (ERG) in CRVO eyes. The
      purpose of this study was to compare aqueous VEGF levels and ERG components
      between hCRVO and BRVO eyes. METHODS: The medical records of patients with
      macular edema secondary to hCRVO (12 eyes) or BRVO (16 eyes) and received an
      intravitreal injection of bevacizumab (IVB) at the Nagoya University Hospital
      from July 2009 to May 2013 were reviewed. Full-field ERGs were recorded before
      the IVB. Aqueous humor was collected just before the IVB to measure VEGF
      concentration. Differences in aqueous VEGF level and ERG components between hCRVO
      and BRVO eyes were determined. RESULTS: Mean aqueous VEGF concentration in hCRVO
      eyes was significantly higher than that in BRVO eyes (504 vs. 148 pg/ml, P <
      0.05). The implicit time of 30-Hz flicker ERG was significantly longer in hCRVO
      than in BRVO eyes (33.5 vs. 29.8 ms, P < 0.01). CONCLUSION: The significant
      difference in VEGF levels in aqueous and implicit times of 30-Hz flicker ERG
      suggest that retinal ischemia is more manifest in hCRVO than in BRVO eyes.

PMID- 24668134
TI  - Long-term outcome of second-line antiretroviral therapy in resource-limited
      settings.
AB  - There is limited information on efficacy and durability of second-line
      antiretroviral therapy (2NL) beyond 12 months in resource-limited settings. A
      total of 73 patients were enrolled into a prospective 2NL observational cohort in
      Nigeria. Second-line antiretroviral therapy consisted of lopinavir/ritonavir plus
      nucleoside reverse transcriptase inhibitors. Time on 2NL ranged from 15 to 31
      months. Genotypes were retrospectively done and not available to guide second
      line regimen choice. At enrollment, median CD4 count was 121 cells/mm3, and
      median time on first-line antiretroviral therapy (ISL) was 24 months. At 6 to 9
      months on 2NL, 72.6% (intention to treat [ITT]) and 88.3% (on treatment [OT]) had
      an undetectable viral load (UDVL). At 12 months, 65.8% (ITT) and 90.57% (OT) had
      UDVL. At >12 to 24 months and at >24 months, 57.5% (ITT) and 91.3% (OT) had UDVL.
      No statistically significant association was observed between CD4 at 2NL start,
      sex, genotypic sensitivity score of 2NL, or tenofovir (TDF) use in ISL and viral
      suppression. Two patients developed major protease inhibitor mutations while on
      2NL. We observed a high degree of viral suppression at 12 months and little loss
      of viral suppression thereafter.

PMID- 24668135
TI  - Relationship of vitamin D, HIV, HIV treatment, and lipid levels in the Women's
      Interagency HIV Study of HIV-infected and uninfected women in the United States.
AB  - Relationships between vitamin D, lipids, HIV infection, and HIV treatment (+/
      antiretroviral therapy [ART]) were investigated with Women's Interagency HIV
      Study data (n = 1758 middle-aged women) using multivariable regression. Sixty
      three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25
      OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P <
      .001) and was the same in HIV-uninfected or HIV-infected women without ART (14
      ng/mL). Vitamin D levels were lower if efavirenz (EFV) was included in ART (15
      versus 19 ng/mL; P < .001). The most common lipid abnormality was high
      triglycerides (>=200 mg/dL) in HIV-infected + ART-treated women (13% versus 7% of
      HIV-infected without ART and 5% of HIV-uninfected; P < .001), with a positive
      relationship between 25-OH vitamin D and triglycerides (95% confidence interval
      0.32-1.69; P < .01). No relationships between 25-OH vitamin D and cholesterol
      were detected. Vitamin D deficiency is common irrespective of HIV status but
      influenced by HIV treatment. Similarly, vitamin D levels were positively related
      to triglycerides only in ART-treated HIV-infected women and unrelated to
      cholesterol. 

PMID- 24668137
TI  - Oral antiplatelet therapy for acute ischaemic stroke.
AB  - BACKGROUND: In people with acute ischaemic stroke, platelets become activated and
      can cause blood clots to form and block an artery in the brain, resulting in
      damage to part of the brain. Such damage gives rise to the symptoms of stroke.
      Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and
      also reduce the risk of early recurrent ischaemic stroke, thereby reducing the
      risk of early death and improving long-term outcomes in survivors. However,
      antiplatelet therapy might also increase the risk of fatal or disabling
      intracranial haemorrhage. OBJECTIVES: To assess the efficacy and safety of
      immediate oral antiplatelet therapy (that is started as soon as possible and no
      later than two weeks after stroke onset) in people with acute presumed ischaemic
      stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register
      (last searched 16 October 2013), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library Issue 4, 2013), MEDLINE (June 1998 to May
      2013), and EMBASE (June 1998 to May 2013). In 1998, for a previous version of
      this review, we searched the register of the Antiplatelet Trialists'
      Collaboration, MedStrategy and contacted relevant drug companies. SELECTION
      CRITERIA: Randomised trials comparing oral antiplatelet therapy (started within
      14 days of the stroke) with control in people with definite or presumed ischaemic
      stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied
      the inclusion criteria and assessed trial quality. For the included trials, they
      extracted and cross-checked the data. MAIN RESULTS: We included eight trials
      involving 41,483 participants. No new trials have been added since the last
      update.Two trials testing aspirin 160 mg to 300 mg once daily, started within 48
      hours of onset, contributed 98% of the data. The risk of bias was low. The
      maximum follow-up was six months. With treatment, there was a significant
      decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95,
      95% confidence interval (CI) 0.91 to 0.99). For every 1000 people treated with
      aspirin, 13 people would avoid death or dependency (number needed to treat 79).
      Antiplatelet therapy was associated with a small but definite excess of
      symptomatic intracranial haemorrhages, but this small hazard was significantly
      outnumbered by the benefit, the reduction in recurrent ischaemic stroke and
      pulmonary embolus. AUTHORS' CONCLUSIONS: Antiplatelet therapy with aspirin 160 mg
      to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who
      cannot swallow) and started within 48 hours of onset of presumed ischaemic
      stroke, reduced the risk of early recurrent ischaemic stroke without a major risk
      of early haemorrhagic complications; long-term outcomes were improved.

PMID- 24668136
TI  - Development of novel ionic liquid-based microemulsion formulation for dermal
      delivery of 5-Fluorouracil.
AB  - The present study was aimed at synthesizing an imidazole-based ionic liquid 1
      butyl-3-methylimidazolium bromide (BMIMBr) and subsequent development of a novel
      ionic liquid-in-oil (IL/o) microemulsion (ME) system for dermal delivery of a
      poorly permeating drug 5-fluorouracil (5-FU). A significant enhancement in the
      solubility of 5-FU was observed in BMIMBr. IL/o MEs of 5-FU were prepared using
      isopropyl myristate, Tween 80/Span 20, and BMIMBr. Results of ex vivo skin
      permeation studies through mice skin indicated that the selected IL/o ME
      exhibited 4-fold enhancement in percent drug permeation as compared to aqueous
      solution, 2.3-fold as compared to hydrophilic ointment, and 1.6-fold greater
      permeation than water in oil (w/o) ME. The results of in vivo studies against
      dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)
      induced mice skin carcinogenesis demonstrated that the IL/o ME could effectively
      treat skin cancer in 4 weeks. In addition, the side effects such as erythema and
      irritation associated with the conventional formulations were not observed.
      Histopathological studies showed that the use of IL/o ME caused no anatomic and
      pathological changes in the skin structure of mice. These studies suggest that
      the use of IL-based ME system can efficiently enhance the solubility and
      permeability of 5-FU and hence its therapeutic efficacy. 

PMID- 24668139
TI  - Medication use as an outcome variable in environmental (noise) epidemiology.

PMID- 24668138
TI  - Chronic kidney disease after autologous stem cell transplantation: analysis of a
      single center experience.
AB  - PURPOSE: Chronic kidney disease (CKD) after allogeneic hematopoietic stem cell
      transplantation (HSCT) has increasingly been reported. However, CKD after
      autologous HSCT, especially changes in renal pathology, has rarely been reported.
      This study aimed to evaluate the frequency of CKD among patients who received
      autologous HSCT for hematological and nonhematological disorders, and analyze its
      clinical and pathological features. METHODS: We performed a retrospective study
      to evaluate the frequency of CKD after autologous HSCT and analyzed clinical and
      pathological features of CKD. Clinical records of patients who underwent
      autologous HSCT at the First Affiliated Hospital of Guangxi Medical University
      between May 2000 and November 2010 were screened. Clinical data of those with
      kidney injury on presentation and follow-up were acquired from hospital records.
      RESULTS: A total of 41 patients who received autologous HSCT were identified. CKD
      developed in six patients (14.6%). Among the six patients, all had various
      degrees of proteinuria and three patients had nephrotic syndrome. Impaired renal
      function occurred in three patients. Three patients with nephrotic syndrome
      received only prednisone. Two patients obtained complete remission, and one had
      partial remission. What is particularly worth mentioning is, in two patients who
      received renal biopsy in our study, the pathological changes were mesangial
      proliferative glomerulonephritis. CONCLUSIONS: Mesangial proliferative
      glomerulonephritis may not be as uncommon as previously thought in CKD patients
      after autologous HSCT. Presentation of nephrotic syndrome is common in CKD after
      HSCT and prednisone alone are effective.

PMID- 24668140
TI  - Quantitative measurement of the nanoparticle size and number concentration from
      liquid suspensions by atomic force microscopy.
AB  - Microscopy techniques are indispensable to the nanoanalytical toolbox and can
      provide accurate information on the number size distribution and number
      concentration of nanoparticles (NPs) at low concentrations (ca. ppt to ppb range)
      and small sizes (ca. <20 nm). However, the high capabilities of microscopy
      techniques are limited by the traditional sample preparation based on drying a
      small volume of suspension of NPs on a microscopy substrate. This method is
      limited by low recovery of NPs (ca. <10%), formation of aggregates during the
      drying process, and thus, the complete misrepresentation of the NP suspensions
      under consideration. This paper presents a validated quantitative sampling
      technique for atomic force microscopy (AFM) that overcomes the above-mentioned
      shortcomings and allows full recovery and representativeness of the NPs under
      consideration by forcing the NPs into the substrate via ultracentrifugation and
      strongly attaches the NPs to the substrate by surface functionalization of the
      substrate or by adding cations to the NP suspension. The high efficiency of the
      analysis is demonstrated by the uniformity of the NP distribution on the
      substrate (that is low variability between the number of NPs counted on different
      images on different areas of the substrate), the high recovery of the NPs up to
      71%) and the good correlation (R > 0.95) between the mass and number
      concentrations. Therefore, for the first time, we developed a validated
      quantitative sampling technique that enables the use of the full capabilities of
      microscopy tools to quantitatively and accurately determine the number size
      distribution and number concentration of NPs at environmentally relevant low
      concentrations (i.e. 0.34-100 ppb). This approach is of high environmental
      relevance and can be applied widely in environmental nanoscience and
      nanotoxicology for (i) measuring the number concentration dose in
      nanotoxicological studies and (ii) accurately measuring the number size
      distribution of NPs; both are key requirements for the implementation of the
      European Commission recommendation for definition of nanomaterials. 

PMID- 24668141
TI  - Interactions between alkanes and aromatic molecules: a rotational study of
      pyridine-methane.
AB  - The rotational spectrum of the adduct pyridine-methane shows that methane links
      to an aromatic molecule apparently through a C-H...pi weak hydrogen bond. The
      shape and the internal dynamics behaviour of this complex are very similar to
      that of the van der Waals complexes involving aromatic molecules with rare gases.

PMID- 24668142
TI  - Crystallinity-driven morphological ripening processes for poly(ethylene oxide)
      block-polycaprolactone micelles in water.
AB  - A set of morphological transformations induced by core crystallization within
      spherical micelle-like aggregates of poly(ethylene oxide)-block-polycaprolactone
      (PEO-b-PCL) is described in the present article. The initial self-assembly step,
      in which individual copolymer chains associate to form the spheres, can be
      performed reproducibly; the stability of these spheres, however, seems to be
      limited, as both transmission electron microscopy and light scattering data
      suggest that the primary spheres transform slowly into elongated rod-like or
      ribbon-like aggregates when suspended in deionized water at room temperature.
      Although the sphere-to-rod transition takes place typically over a time scale of
      several days, the formation of individual rods from spheres is very rapid, as
      evidenced by the progressive increase in the number of long rods and the
      conspicuous absence of short rods. 

PMID- 24668143
TI  - Differential effects of acute and chronic zinc exposure on lipid metabolism in
      three extrahepatic tissues of juvenile yellow catfish Pelteobagrus fulvidraco.
AB  - The aim of this study was to determine the potential mechanisms of exposure to
      waterborne zinc (Zn) on lipid metabolism in three extrahepatic tissues (ovary,
      muscle and mesenteric adipose tissue) of female yellow catfish Pelteobagrus
      fulvidraco. Female yellow catfish were chronically exposed to Zn (0.05, 0.35 or
      0.86 mg Zn/l; duration of treatment 8 weeks) or acutely exposed to a high level
      of Zn (4.71 mg Zn/l for 96 h). Following the respective treatment, lipid
      deposition and mRNA levels of 11 genes (CPT IA, CPT IB, PPARalpha, PPARgamma,
      SREBP-1, G6PD, 6PGD, FAS, ACCa, ACCb and LPL) involved in lipid metabolism were
      determined. Waterborne Zn exposure significantly reduced growth performance and
      lipid content in muscle but had no significant effect on lipid content in ovary
      and mesenteric adipose tissue. The change in the levels of the mRNA genes under
      study was Zn concentration-dependent and tissue-dependent. Pearson correlations
      between the mRNA levels of three transcriptional factors and enzymes in these
      tissues revealed that variations in gene expression as a result of the different
      Zn treatments underlay the patterns of lipid metabolism, which in turn affected
      fat storage and mobilization. To our knowledge, this is the first study to
      demonstrate the effect of waterborne Zn exposure on lipid metabolism in
      extrahepatic tissues at the molecular level. These results therefore contribute
      to our understanding of Zn-induced toxicity in fish.

PMID- 24668144
TI  - Conservative management of significant supratentorial epidural hematomas in
      pediatric patients.
AB  - BACKGROUND: Radiologically significant epidural hematomas are generally treated
      with craniotomy and evacuation. However, pediatric patients with such hematomas
      may have normal neurological examinations. We aim to report the presenting
      features, management, and outcomes of pediatric patients who underwent
      conservative management of such hematomas at our center and also show that serial
      neurological examinations are a safe and effective way of managing these
      patients. METHODS: A retrospective review of pediatric patients with extradural
      hematoma (EDH) thickness of at least 1 cm and who were conservatively managed was
      performed. All patients were followed up in neurosurgery outpatient clinics after
      discharge at 1-month, 3-month, 6-month, and 1-year intervals. Detailed
      neurological examination was performed at each visit, and a standardized
      questionnaire was also used to document the parent's subjective opinion of the
      patient's quality of life. RESULTS: A total of 17 patients satisfied the study
      criteria and were included. Conservative management was successful in 15
      patients, while a craniotomy with evacuation of hematoma had to be performed in
      two patients. All patients had a GOS score of 5 on 1-year follow-up, had normal
      schooling, and reported complete satisfaction with the management protocol.
      CONCLUSION: Conservative treatment is an optimal treatment option, and patients
      can be followed safely using a protocol of serial neurological examinations. A
      center must have resources to perform a craniotomy with evacuation of EDH in case
      of neurological worsening and be able to provide trained staff to carry out
      serial neurological examinations before treating these patients conservatively.

PMID- 24668145
TI  - How amphipols embed membrane proteins: global solvent accessibility and
      interaction with a flexible protein terminus.
AB  - Amphipathic polymers called amphipols provide a valuable alternative to
      detergents for keeping integral membrane proteins soluble in aqueous buffers.
      Here, we characterize spatial contacts of amphipol A8-35 with membrane proteins
      from two architectural classes: The 8-stranded beta-barrel outer membrane protein
      OmpX and the alpha-helical protein bacteriorhodopsin. OmpX is well structured in
      A8-35, with its barrel adopting a fold closely similar to that in
      dihexanoylphosphocholine micelles. The accessibility of A8-35-trapped OmpX by a
      water-soluble paramagnetic molecule is highly similar to that in detergent
      micelles and resembles the accessibility in the natural membrane. For the alpha
      helical protein bacteriorhodopsin, previously shown to keep its fold and function
      in amphipols, NMR data show that the imidazole protons of a polyhistidine tag at
      the N-terminus of the protein are exchange protected in the presence of detergent
      and lipid bilayer nanodiscs, but not in amphipols, indicating the absence of an
      interaction in the latter case. Overall, A8-35 exhibits protein interaction
      properties somewhat different from detergents and lipid bilayer nanodiscs, while
      maintaining the structure of solubilized integral membrane proteins. 

PMID- 24668146
TI  - Bimetallic Pd-Cu nanocrystals and their tunable catalytic properties.
AB  - Monodisperse Pd-Cu bimetallic nanocrystals (NCs) with tunable compositions
      (Pd0.2Cu0.8, Pd0.3Cu0.7, Pd0.5Cu0.5, Pd0.7Cu0.3, Pd0.8Cu0.2) and controlled sizes
      (5.2 nm, 6.8 nm, 8.1 nm, 16.4 nm, 19.9 nm) were easily obtained in an
      octadecylamine (ODA) synthetic system, which exhibited tunable catalytic
      properties for styrene epoxidation and ethanol electro-oxidation. 

PMID- 24668147
TI  - Resection of pulmonary metastases from colon and rectal cancer: factors to
      predict survival differ regarding to the origin of the primary tumor.
AB  - BACKGROUND: The purpose of the present study was to determine differences in
      prognostic factors for survival of patients with pulmonary metastases resected in
      curative intent from colon or rectum cancer. METHODS: Between 1980 and 2006,
      prognostic factors after resection of pulmonary metastases in 171 patients with
      primary rectum or colon tumor were evaluated. Survival of patients after surgical
      metastasectomy was compared with that of patients receiving standard chemotherapy
      by matched-pair analysis. RESULTS: Median survival after pulmonary resection was
      35.2 months (confidence interval 27.3-43.2). One-, 3-, and 5-year survival for
      patients following R0 resection was 88.8, 52.1, and 32.9 % respectively. Complete
      metastasectomy (R0), UICC stage of the primary tumor, pleural infiltration, and
      hilar or mediastinal lymph node metastases are independent prognostic factors for
      survival. Matched-pair analysis confirmed that pulmonary metastasectomy
      significantly improved survival. Although no difference in survival for patients
      with pulmonary metastases from lower rectal compared to upper rectal or colon
      cancer was observed, factors to predict survival are different for patients with
      lower and middle rectal cancer (R0, mediastinal and/or hilar lymph nodes, gender,
      UICC stage) compared with patients with upper rectal or colon cancer (R0, number
      of metastases). CONCLUSIONS: Our results indicate that distinct prognostic
      factors exist for patients with pulmonary metastases from lower rectal compared
      with upper rectal or colon cancer. This supports the notion that colorectal
      cancer should not be considered as a single-tumor entity. Metastasectomy,
      especially after complete resection resulted in a dramatic improvement of
      survival compared with patients treated with chemotherapy alone.

PMID- 24668148
TI  - Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the
      curative management of peritoneal colorectal carcinomatosis.
AB  - PURPOSE: The primary objective of this study was to determine the incidence rate
      of pathological complete responses (pCRs) following neoadjuvant systemic
      chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal
      origin. The secondary objective was to evaluate whether pathological response
      assessments predict survival of patients treated with curative intent by complete
      cytoreductive surgery (CRS). METHODS: A retrospective review was performed of 115
      patients who underwent preoperative irinotecan- or oxaliplatin-based
      chemotherapy, followed by 124 procedures of complete CRS alone or combined with
      hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was
      defined as the mean percentage of cancer cells remaining within all specimens.
      Univariate and multivariate analyses were performed to identify predictors of
      survival and pathological response outcome. RESULTS: Twelve procedures (9.7 %)
      resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2
      %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %)
      resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5
      year survival rates were 75 and 57 % for patients with pCR and major responses,
      respectively. Using multivariate analysis, pathological response was the only
      independent predictor of survival (P = 0.01; major response: hazard ratio [HR] =
      4.91; minor response: HR = 13.46). No significant predictor of pathological
      response was identified. CONCLUSIONS: Pathological complete response can be
      achieved with preoperative systemic chemotherapy for patients with PC of
      colorectal origin. The degree of pathological response can be assessed and
      represented as a new outcome for prognosis following treatment with curative
      intent.

PMID- 24668150
TI  - MnO2 nanolayers on highly conductive TiO(0.54)N(0.46) nanotubes for
      supercapacitor electrodes with high power density and cyclic stability.
AB  - Pseudo-capacitive MnO2 supercapacitors are attracting intense interest because of
      the theoretically high specific capacitance (1370 F g(-1)) and low cost of MnO2.
      For the practical application, the power density and the cyclic stability of MnO2
      based supercapacitors are expected to be improved. Increasing the efficiency of
      the current collection is an effective method to improve the power density for a
      given supercapacitor. Here, the highly conductive and electrochemically stable
      material, titanium oxynitride (TiO0.54N0.46), is used as the current collector.
      Uniform amorphous MnO2 nanolayers were deposited on metal-phase TiO0.54N0.46
      nanotube arrays using a modified electrochemical deposition method. The resulting
      MnO2 supercapacitors exhibited a high power density of 620 kW kg(-1) at an energy
      density of 9.8 W h kg(-1). This is comparable to high-performance carbon-based
      electrochemical double layer capacitors in aqueous electrolytes. The high
      electron transport was enhanced with a highly conductive TiO0.54N0.46 scaffold.
      Ion transport was promoted in the nanotube structures that had porous walls. In
      addition, the close interfacial connection between MnO2 and TiO0.54N0.46
      contributed to the excellent cyclic stability (ca. 92.0% capacitance retention
      after 100 000 cycles). These results indicated that the highly conductive and
      electrochemically stable titanium oxynitride is an excellent candidate for use as
      an electrode material in high performance supercapacitors. 

PMID- 24668151
TI  - Alternative splice variants of AID are not stoichiometrically present at the
      protein level in chronic lymphocytic leukemia.
AB  - Activation-induced deaminase (AID) is a DNA-mutating enzyme that mediates class
      switch recombination as well as somatic hypermutation of antibody genes in B
      cells. Due to off-target activity, AID is implicated in lymphoma development by
      introducing genome-wide DNA damage and initiating chromosomal translocations such
      as c-myc/IgH. Several alternative splice transcripts of AID have been reported in
      activated B cells as well as malignant B cells such as chronic lymphocytic
      leukemia (CLL). As most commercially available antibodies fail to recognize
      alternative splice variants, their abundance in vivo, and hence their biological
      significance, has not been determined. In this study, we assessed the protein
      levels of AID splice isoforms by introducing an AID splice reporter construct
      into cell lines and primary CLL cells from patients as well as from WT and
      TCL1(tg) C57BL/6 mice (where TCL1 is T-cell leukemia/lymphoma 1). The splice
      construct is 5'-fused to a GFP-tag, which is preserved in all splice isoforms and
      allows detection of translated protein. Summarizing, we show a thorough
      quantification of alternatively spliced AID transcripts and demonstrate that the
      corresponding protein abundances, especially those of splice variants AID-ivs3
      and AID-DeltaE4, are not stoichiometrically equivalent. Our data suggest that
      enhanced proteasomal degradation of low-abundance proteins might be causative for
      this discrepancy. 

PMID- 24668152
TI  - Design of phosphated cross-linked microspheres of bael fruit gum as a
      biodegradable carrier.
AB  - Present work was aimed at designing of phosphated cross-linked microspheres of
      bael fruit gum (BFG) by emulsification method using sodium-tri-meta phosphate as
      a cross-linking agent for treatment of colon cancer using 5-fluorouracil as model
      drug. Stirring speed was found to be 1,000 rpm for about 5 h to be optimal to
      obtain reproducible microspheres. It was found that there is an increase in
      particle size as polymer concentration is increased whereas a reduction in
      particle size was observed as there is increase in stirring speed. Cross-linked
      BFG microspheres were successfully prepared by emulsification method. Optimum
      surfactant concentration was found to be 2 % w/w. Scanning electron microscopy
      studies showed that the drug-loaded microspheres were non-aggregated and in
      spherical shape. Differential scanning calorimetry and Fourier transform infrared
      spectroscopy studies showed that drug and excipients are compatible. Release
      studies showed that drug release was more profound in cecal medium induced with
      enzymes causing degradation of the cross linked BFG than that of the release
      showed in simulated intestinal fluid. Stability studies showed that there were no
      significant changes in the drug content and physical appearance of microspheres. 

PMID- 24668153
TI  - Aloin protects against chronic alcoholic liver injury via attenuating lipid
      accumulation, oxidative stress and inflammation in mice.
AB  - The present study was designed to investigate the protective effect of aloin
      against alcoholic liver disease in a chronic alcohol feeding mouse model. Mice
      were given alcohol twice a day by intragastric administration for 11 weeks (4.0,
      4.7, 5.5 g/kg bw/day for the first 3 weeks respectively, 6.3 g/kg bw/day for the
      following 8 weeks). Aloin (10, 30 mg/kg bw) or vehicle was given by gavage to
      mice after each alcohol administration. Alcohol elevated the serum transaminases
      alanine aminotransferase, aspartate aminotransferase, total cholesterol and
      triglyceride levels which were significantly attenuated by the co-administration
      of aloin (p < 0.05). Histopathological observations were consistent with these
      indices. Co-administration of aloin significantly suppressed the alcohol
      dependent induction of sterol regulatory element-binding protein-1c expression (p
      < 0.01) and remarkably up-regulated the mRNA levels of AMP-activated protein
      kinase-alpha2 (p < 0.001). Furthermore, aloin supplementation significantly
      inhibited the alcohol-dependent elevation of malondialdehyde and cytochrome
      P4502E1 expression (p < 0.05), and significantly elevated superoxide dismutase
      activity (p < 0.01). The up-regulation of serum lipopolysaccharide (LPS), hepatic
      nitric oxide, tumor necrosis factor alpha, toll-like receptor-4, and myeloid
      differentiation primary response gene 88 were also markedly suppressed by the co
      administration of aloin (p < 0.05) in alcohol-treated mice. These results suggest
      that aloin may represent a novel, protective strategy against chronic alcoholic
      liver injury by attenuating lipid accumulation, oxidative stress and LPS-induced
      inflammatory response.

PMID- 24668154
TI  - Diphenyl derivatives from coastal saline soil fungus Aspergillus iizukae.
AB  - Two new diphenyl derivatives, named iizukines A (1) and B (2), along with nine
      known compounds were isolated from coastal saline soil derived fungus Aspergillus
      iizukae. The structures were determined by extensive spectroscopic analysis.
      Their cytotoxicities were preliminarily evaluated on HL-60, BEL-7402 and A-549
      cell lines by the MTT assay. 

PMID- 24668155
TI  - Alloxan-induced diabetic thermal hyperalgesia, prophylaxis and phytotherapeutic
      effects of Rheum ribes L. in mouse model.
AB  - Rheum ribes L., known as Syrian rhubarb, is used in traditional Lebanese folk
      medicine for the treatment of diabetes. The present study aims to investigate the
      activities of R. ribes aqueous extract for glucose homeostasis, in vivo
      antioxidant and diabetic neuropathy protection in mice. The acute and the
      subacute effects of various doses of R. ribes on blood glucose and in vivo
      antioxidant activity utilizing serum catalase level (CAT) were studied in alloxan
      diabetic mice. The high doses significantly lowered glucose level and increased
      serum CAT in alloxan-diabetic mice. Pretreatment with the extract prior to
      alloxination, protected the mice from acquiring diabetes and diabetic neuropathy.
      Treatment with the extract for 8 weeks alleviated hyperalgesia in diabetic mice.
      Our findings provide clinicians with promising drugs intended for the management
      of the symptoms of diabetic complications. The protective activity of R. ribes
      against acquiring diabetes and diabetic neuropathy might pave the way for
      preparing a prophylactic treatment for diabetes risk groups.

PMID- 24668156
TI  - Biofeedback for treatment of chronic idiopathic constipation in adults.
AB  - BACKGROUND: Biofeedback therapy has been used to treat the symptoms of people
      with chronic constipation referred to specialist services within secondary and
      tertiary care settings. However, different methods of biofeedback are used within
      different centres and the magnitude of suggested benefits and comparable
      effectiveness of different methods of biofeedback has yet to be established.
      OBJECTIVES: To determine the efficacy and safety of biofeedback for the treatment
      of chronic idiopathic (functional) constipation in adults. SEARCH METHODS: We
      searched the following databases from inception to 16 December 2013: CENTRAL, the
      Cochrane Complementary Medicine Field, the Cochrane IBD/FBD Review Group
      Specialized Register, MEDLINE, EMBASE, CINAHL, British Nursing Index, and
      PsychINFO. Hand searching of conference proceedings and the reference lists of
      relevant articles was also undertaken. SELECTION CRITERIA: All randomised trials
      evaluating biofeedback in adults with chronic idiopathic constipation were
      considered for inclusion. DATA COLLECTION AND ANALYSIS: The primary outcome was
      global or clinical improvement as defined by the included studies. Secondary
      outcomes included quality of life, and adverse events as defined by the included
      studies. Where possible, we calculated the risk ratio (RR) and corresponding 95%
      confidence interval (CI) for dichotomous outcomes and the mean difference (MD)
      and 95% CI for continuous outcomes. We assessed the methodological quality of
      included studies using the Cochrane risk of bias tool. The overall quality of the
      evidence supporting each outcome was assessed using the GRADE criteria. MAIN
      RESULTS: Seventeen eligible studies were identified with a total of 931
      participants. Most participants had chronic constipation and dyssynergic
      defecation. Sixteen of the trials were at high risk of bias for blinding.
      Attrition bias (4 trials) and other potential bias (5 trials) was also noted. Due
      to differences between study populations, the heterogeneity of the different
      samples and large range of different outcome measures, meta-analysis was not
      possible. Different effect sizes were reported ranging from 40 to 100% of
      patients who received biofeedback improving following the intervention. While
      electromyograph (EMG) biofeedback was the most commonly used, there is a lack of
      evidence as to whether any one method of biofeedback is more effective than any
      other method of biofeedback. We found low or very low quality evidence that
      biofeedback is superior to oral diazepam, sham biofeedback and laxatives. One
      study (n = 60) found EMG biofeedback to be superior to oral diazepam. Seventy per
      cent (21/30) of biofeedback patients had improved constipation at three month
      follow-up compared to 23% (7/30) of diazepam patients (RR 3.00, 95% CI 1.51 to
      5.98). One study compared manometry biofeedback to sham biofeedback or standard
      therapy consisting of diet, exercise and laxatives. The mean number of complete
      spontaneous bowel movements (CSBM) per week at three months was 4.6 in the
      biofeedback group compared to 2.8 in the sham biofeedback group (MD 1.80, 95% CI
      1.25 to 2.35; 52 patients). The mean number of CSBM per week at three months was
      4.6 in the biofeedback group compared to 1.9 in the standard care group (MD 2.70,
      95% CI 1.99 to 3.41; 49 patients). Another study (n = 109) compared EMG
      biofeedback to conventional treatment with laxatives and dietary and lifestyle
      advice. This study found that at both 6 and 12 months 80% (43/54) of biofeedback
      patients reported clinical improvement compared to 22% (12/55) laxative-treated
      patients (RR 3.65, 95% CI 2.17 to 6.13). Some surgical procedures (partial
      division of puborectalis and stapled transanal rectal resection (STARR)) were
      reported to be superior to biofeedback, although with a high risk of adverse
      events in the surgical groups (wound infection, faecal incontinence, pain, and
      bleeding that required further surgical intervention). Successful treatment,
      defined as a decrease in the obstructed defecation score of > 50% at one year was
      reported in 33% (3/39) of EMG biofeedback patients compared to 82% (44/54) of
      STARR patients (RR 0.41, 95% CI 0.26 to 0.65). For the other study the mean
      constipation score at one year was 16.1 in the balloon sensory biofeedback group
      compared to 10.5 in the partial division of puborectalis surgery group (MD 5.60,
      95% CI 4.67 to 6.53; 40 patients). Another study (n = 60) found no significant
      difference in efficacy did not demonstrate the superiority of a surgical
      intervention (posterior myomectomy of internal anal sphincter and puborectalis)
      over biofeedback. Conflicting results were found regarding the comparative
      effectiveness of biofeedback and botulinum toxin-A. One small study (48
      participants) suggested that botulinum toxin-A injection may have short term
      benefits over biofeedback, but the relative effects of treatments were uncertain
      at one year follow-up. No adverse events were reported for biofeedback, although
      this was not specifically reported in the majority of studies. The results of all
      of these studies need to be interpreted with caution as GRADE analyses rated the
      overall quality of the evidence for the primary outcomes (i.e. clinical or global
      improvement as defined by the studies) as low or very low due to high risk of
      bias (i.e. open label studies, self-selection bias, incomplete outcome data, and
      baseline imbalance) and imprecision (i.e. sparse data). AUTHORS' CONCLUSIONS:
      Currently there is insufficient evidence to allow any firm conclusions regarding
      the efficacy and safety of biofeedback for the management of people with chronic
      constipation. We found low or very low quality evidence from single studies to
      support the effectiveness of biofeedback for the management of people with
      chronic constipation and dyssynergic defecation. However, the majority of trials
      are of poor methodological quality and subject to bias. Further well-designed
      randomised controlled trials with adequate sample sizes, validated outcome
      measures (especially patient reported outcome measures) and long-term follow-up
      are required to allow definitive conclusions to be drawn.

PMID- 24668157
TI  - Complete genome sequence of 285P, a novel T7-like polyvalent E. coli
      bacteriophage.
AB  - Bacteriophages are considered potential biological agents for the control of
      infectious diseases and environmental disinfection. Here, we describe a novel T7
      like polyvalent Escherichia coli bacteriophage, designated "285P," which can lyse
      several strains of E. coli. The genome, which consists of 39,270 base pairs with
      a G+C content of 48.73 %, was sequenced and annotated. Forty-three potential open
      reading frames were identified using bioinformatics tools. Based on whole-genome
      sequence comparison, phage 285P was identified as a novel strain of subgroup T7.
      It showed strongest sequence similarity to Kluyvera phage Kvp1. The phylogenetic
      analyses of both non-structural proteins (endonuclease gp3, amidase gp3.5, DNA
      primase/helicase gp4, DNA polymerase gp5, and exonuclease gp6) and structural
      protein (tail fiber protein gp17) led to the identification of 285P as T7-like
      phage. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix
      assisted laser desorption/ionization time-of-flight mass spectrometric analyses
      verified the annotation of the structural proteins (major capsid protein gp10a,
      tail protein gp12, and tail fiber protein gp17).

PMID- 24668158
TI  - Interaction of a potential chloride channel blocker with a model transport
      protein: a spectroscopic and molecular docking investigation.
AB  - The present work demonstrates a detailed characterization of the interaction of a
      potential chloride channel blocker, 9-methyl anthroate (9-MA), with a model
      transport protein, Bovine Serum Albumin (BSA). The modulated photophysical
      properties of the emissive drug molecule within the microheterogeneous bio
      environment of the protein have been exploited spectroscopically to monitor the
      probe-protein binding interaction. Apart from evaluating the binding constant,
      the probable location of the neutral molecule within the protein cavity
      (subdomain IB) is explored by an AutoDock-based blind docking simulation. The
      absence of the Red-Edge Effect has been corroborated by the enhanced lifetime of
      the probe, being substantially greater than the solvent reorientation time. A dip
      and-rise characteristic of the rotational relaxation profile of the drug within
      the protein has been argued to originate from a significant difference in the
      lifetime as well as amplitude of the free and protein-bound drug molecule.
      Unfolding of the protein in the presence of the drug molecule has been probed by
      the decrease of the alpha-helical content, obtained via circular dichroism (CD)
      spectroscopy, which is also supported by the gradual loss of the esterase
      activity of the protein in the presence of the drug molecule. 

PMID- 24668159
TI  - A Review of and Recommendations for the Management of Patients With Life
      Threatening Dabigatran-Associated Hemorrhage: A Single-Center University Hospital
      Experience.
AB  - Dabigatran is an oral direct thrombin inhibitor that is approved for the
      prevention of stroke and systemic embolism in nonvalvular atrial fibrillation.
      Dabigatran has several advantages over warfarin including predictable
      pharmacokinetics and pharmacodynamics which eliminates the need for routine
      laboratory monitoring, superiority over warfarin in preventing stroke, or
      systemic embolism without having an increased risk of bleeding. However, as with
      any anticoagulant, there remains a real chance of bleeding, including major or
      life-threatening hemorrhage. Many physicians feel comfortable managing bleeding
      complications on older anticoagulants like warfarin and heparin, due to extensive
      experience with the medications along with antidotes to reverse their effects as
      well as established protocols for treating anticoagulant-associated hemorrhage.
      However, most physicians have limited clinical experience with dabigatran, there
      is no specific antidote for dabigatran reversal and there is a paucity of
      protocols, guidelines, and recommendations for how to manage dabigatran
      associated hemorrhage. In this review, we present a case series of patients
      admitted to our institution for management of bleeding while receiving
      dabigatran. We retrospectively reviewed these cases to evaluate the efficacy and
      rationale of the various anticoagulation reversal strategies employed in the
      context of the existing evidence found in the literature. Specific focus is
      placed on the therapies utilized and the coagulation studies used to manage these
      patients. 

PMID- 24668160
TI  - Attachment/detachment hysteresis of fiber-based magnetic grabbers.
AB  - We developed an experimental protocol to analyze the behaviour of a model fiber
      based magnetic grabber. A fiber is vertically suspended and fixed to the
      substrate by its upper end. A magnetic droplet is attached to the free end of the
      fiber and when a permanent magnet approaches the droplet, the fiber is forced to
      bow and finally jumps to the magnet. It appears that one can flex the micro
      fibers by very small micro or even nano-Newton forces. Using this setup, we
      discovered a hysteresis of fiber attachment/detachment: the pathway of the fiber
      jumping to and off the magnet depends on the distance between the magnet and the
      clamped end. This phenomenon was successfully explained by the Euler-Benoulli
      model of an elastic beam. The observed hysteresis of fiber attachment/detachment
      was attributed to the multiple equilibrium configurations of the fiber tip placed
      in a dipole-type magnetic field. 

PMID- 24668161
TI  - Effects of dietary copper on nutrient digestibility, tissular copper deposition
      and fur quality of growing-furring mink (Mustela vison).
AB  - The present study investigated the effects of dietary copper (Cu) on growth
      performance and fur quality in growing-furring minks. One hundred and five
      standard dark female minks were randomly assigned to seven groups with the
      following dietary treatments: basal diet with no supplemental Cu (control) and
      basal diet supplemented with either 6, 12, 24, 48, 96 or 192 mg/kg Cu from copper
      sulphate, respectively. Our data showed that final body weight (P = 0.033), daily
      gain (P = 0.029) and fat digestibility (P = 0.0006) responded to increasing
      levels of Cu. The activity of glutamic-oxalacetic transaminase (GOT) and glutamic
      pyruvic transaminase (GPT) in serum increased (linear and quadratic, P < 0.05) as
      Cu increased in the diet. Increasing Cu improved total protein (TP) and albumin
      (ALB) (quadratic, P < 0.05). The level of ceruloplasmin (CER) responded in a
      linear (P < 0.0001) and quadratic (P < 0.0001) form with increasing level of Cu.
      Colour intensity of those minks pelted suggested that relatively high levels of
      supplemental Cu have a beneficial effect on intensifying hair colour of dark mink
      but did not affect leather thickness. Liver Cu and plasma Cu concentrations of
      the mink linearly (P < 0.0001) responded to increasing levels of Cu. Our results
      indicate that growing-furring mink can efficiently utilize added dietary fat and
      that Cu plays an important role in the digestion of dietary fat in growing
      furring mink, and supplemental dietary Cu in growing-furring mink promotes fat
      digestion and improve hair colour.

PMID- 24668162
TI  - Determination of the longest intrapatient left ventricular electrical delay may
      predict acute hemodynamic improvement in patients after cardiac resynchronization
      therapy.
AB  - BACKGROUND: One of the reasons for patient nonresponse to cardiac
      resynchronization therapy is a suboptimal left ventricular (LV) pacing site. LV
      electric delay (Q-LV interval) has been indicated as a prognostic parameter of
      cardiac resynchronization therapy response. This study evaluates the LV delay for
      the optimization of the LV pacing site. METHODS AND RESULTS: Thirty-two
      consecutive patients (23 men; mean age, 71+/-11 years; LV ejection fraction, 30+/
      6%; 18 with ischemic cardiomyopathy; QRS, 181+/-25 ms; all mean+/-SD) underwent
      cardiac resynchronization therapy device implantation. All available tributary
      veins of the coronary sinus were tested, and the Q-LV interval was measured at
      each pacing site. The hemodynamic effects of pacing at different sites were
      evaluated by invasive measurement of LV dP/dtmax at baseline and during pacing.
      Overall, 2.9+/-0.8 different veins and 6.4+/-2.3 pacing sites were tested. In 31
      of 32 (96.8%) patients, the highest LV dP/dtmax coincided with the maximum Q-LV
      interval. Q-LV interval correlated with the increase in LV dP/dtmax in all
      patients at each site (AR1 rho=0.98; P<0.001). A Q-LV value >95 ms corresponded
      to a >10% in LV dP/dtmax. An inverse correlation between paced QRS duration and
      improvement in LV dP/dtmax was seen in 24 patients (75%). CONCLUSIONS: Pacing the
      LV at the latest activated site is highly predictive of the maximum increase in
      contractility, expressed as LV dP/dtmax. A positive correlation between Q-LV
      interval and hemodynamic improvement was found in all patients at every pacing
      site, a value of 95 ms corresponding to an increase in LV dP/dtmax of >=10%.

PMID- 24668163
TI  - Children's responses to hypothetical provocation by peers: coordination of
      assertive and aggressive strategies.
AB  - Children often respond to aggression by peers with assertive bids or aggressive
      retaliation. Little is known, however, about whether and how children coordinate
      these strategies across different types of provocation. The present study
      examined endorsement of aggressive and assertive responses to hypothetical
      physical, relational, and verbal provocation in a sample of lower-income children
      (N = 402, M age = 10.21, SD = 1.46). Latent-profile analysis revealed 3-class
      models for both aggression and assertion, each reflecting low, moderate, and high
      levels of endorsement. There was no association between children's reported use
      of aggression and assertion. For example, children who endorsed high levels of
      aggression were equally likely to be classified as low, moderate, or high on
      assertive responding. For both assertion and aggression, parental ratings of
      children's externalizing behavior and social skills differed across the low and
      high groups. No such differences were found between the low and moderate groups,
      despite the latter groups endorsing markedly higher levels of assertive and
      aggressive responses. This pattern of findings may be due, in part, to the
      situation specificity of children's responding. Our findings hint at the
      complexity of children's behavioral repertoires and contribute to a growing
      literature that suggests the need for intervention models that consider both
      social skills and social situations. 

PMID- 24668164
TI  - Fifth-grade children's daily experiences of peer victimization and negative
      emotions: moderating effects of sex and peer rejection.
AB  - This study examined the relations of fifth-grade children's (181 boys and girls)
      daily experiences of peer victimization with their daily negative emotions.
      Children completed daily reports of peer victimization and negative emotions
      (sadness, anger, embarrassment, and nervousness) on up to eight school days. The
      daily peer victimization checklist was best represented by five factors: physical
      victimization, verbal victimization, social manipulation, property attacks, and
      social rebuff. All five types were associated with increased negative daily
      emotions, and several types were independently linked to increased daily negative
      emotions, particularly physical victimization. Girls demonstrated greater
      emotional reactivity in sadness to social manipulation than did boys, and higher
      levels of peer rejection were linked to greater emotional reactivity to multiple
      types of victimization. Sex and peer rejection also interacted, such that greater
      rejection was a stronger indicator of emotional reactivity to victimization in
      boys than in girls. 

PMID- 24668165
TI  - Evolutionarily conserved and conformationally constrained short peptides might
      serve as DNA recognition elements in intrinsically disordered regions.
AB  - Despite recent advances, it is yet not clear how intrinsically disordered regions
      in proteins recognize their targets without any defined structures. Short linear
      motifs had been proposed to mediate molecular recognition by disordered regions;
      however, the underlying structural prerequisite remains elusive. Moreover, the
      role of short linear motifs in DNA recognition has not been studied. We report a
      repertoire of short evolutionarily Conserved Recognition Elements (CoREs) in long
      intrinsically disordered regions, which have very distinct amino-acid
      propensities from those of known motifs, and exhibit a strong tendency to retain
      their three-dimensional conformations compared to adjacent regions. The majority
      of CoREs directly interact with the DNA in the available 3D structures, which is
      further supported by literature evidence, analyses of DeltaDeltaG values of DNA
      binding energies and threading-based prediction of DNA binding potential. CoREs
      were enriched in cancer-associated missense mutations, further strengthening
      their functional nature. Significant enrichment of glycines in CoREs and the
      preference of glycyl phi-Psi values within the left-handed bridge range in the l
      disallowed region of the Ramachandran plot suggest that Gly-to-nonGly mutations
      within CoREs might alter the backbone conformation and consequently the function,
      a hypothesis that we reconciled using available mutation data. We conclude that
      CoREs might serve as bait for DNA recognition by long disordered regions and that
      certain mutations in these peptides can disrupt their DNA binding potential and
      consequently the protein function. We further hypothesize that the preferred
      conformations of CoREs and of glycyl residues therein might play an important
      role in DNA binding. The highly ordered nature of CoREs hints at a therapeutic
      strategy to inhibit malicious molecular interactions using small molecules
      mimicking CoRE conformations. 

PMID- 24668166
TI  - Local GABA concentration is related to network-level resting functional
      connectivity.
AB  - Anatomically plausible networks of functionally inter-connected regions have been
      reliably demonstrated at rest, although the neurochemical basis of these 'resting
      state networks' is not well understood. In this study, we combined magnetic
      resonance spectroscopy (MRS) and resting state fMRI and demonstrated an inverse
      relationship between levels of the inhibitory neurotransmitter GABA within the
      primary motor cortex (M1) and the strength of functional connectivity across the
      resting motor network. This relationship was both neurochemically and
      anatomically specific. We then went on to show that anodal transcranial direct
      current stimulation (tDCS), an intervention previously shown to decrease GABA
      levels within M1, increased resting motor network connectivity. We therefore
      suggest that network-level functional connectivity within the motor system is
      related to the degree of inhibition in M1, a major node within the motor network,
      a finding in line with converging evidence from both simulation and empirical
      studies. DOI: http://dx.doi.org/10.7554/eLife.01465.001. 

PMID- 24668167
TI  - Acetylation of histone H3 at lysine 64 regulates nucleosome dynamics and
      facilitates transcription.
AB  - Post-translational modifications of proteins have emerged as a major mechanism
      for regulating gene expression. However, our understanding of how histone
      modifications directly affect chromatin function remains limited. In this study,
      we investigate acetylation of histone H3 at lysine 64 (H3K64ac), a previously
      uncharacterized acetylation on the lateral surface of the histone octamer. We
      show that H3K64ac regulates nucleosome stability and facilitates nucleosome
      eviction and hence gene expression in vivo. In line with this, we demonstrate
      that H3K64ac is enriched in vivo at the transcriptional start sites of active
      genes and it defines transcriptionally active chromatin. Moreover, we find that
      the p300 co-activator acetylates H3K64, and consistent with a transcriptional
      activation function, H3K64ac opposes its repressive counterpart H3K64me3. Our
      findings reveal an important role for a histone modification within the
      nucleosome core as a regulator of chromatin function and they demonstrate that
      lateral surface modifications can define functionally opposing chromatin states.
      DOI: http://dx.doi.org/10.7554/eLife.01632.001. 

PMID- 24668168
TI  - The Kinesin-12 Kif15 is a processive track-switching tetramer.
AB  - Kinesin-12 motors are a little studied branch of the kinesin superfamily with the
      human protein (Kif15) implicated in spindle mechanics and chromosome movement. In
      this study, we reconstitute full-length hKif15 and its microtubule-targeting
      factor hTpx2 in vitro to gain insight into the motors mode of operation. We
      reveal that hKif15 is a plus-end-directed processive homotetramer that can step
      against loads of up to 3.5 pN. We further show that hKif15 is the first kinesin
      that effectively switches microtubule tracks at intersections, enabling it to
      navigate microtubule networks, such as the spindle. hKif15 tetramers are also
      capable of cross-linking microtubules, but unexpectedly, this does not depend on
      hTpx2. Instead, we find that hTpx2 inhibits hKif15 stepping when microtubule
      bound. Our data reveal that hKif15 is a second tetrameric spindle motor in
      addition to the kinesin-5 Eg5 and provides insight into the mechanisms by which
      hKif15 and its inhibitor hTpx2 modulate spindle microtubule architecture. DOI:
      http://dx.doi.org/10.7554/eLife.01724.001. 

PMID- 24668169
TI  - Fast transient networks in spontaneous human brain activity.
AB  - To provide an effective substrate for cognitive processes, functional brain
      networks should be able to reorganize and coordinate on a sub-second temporal
      scale. We used magnetoencephalography recordings of spontaneous activity to
      characterize whole-brain functional connectivity dynamics at high temporal
      resolution. Using a novel approach that identifies the points in time at which
      unique patterns of activity recur, we reveal transient (100-200 ms) brain states
      with spatial topographies similar to those of well-known resting state networks.
      By assessing temporal changes in the occurrence of these states, we demonstrate
      that within-network functional connectivity is underpinned by coordinated
      neuronal dynamics that fluctuate much more rapidly than has previously been
      shown. We further evaluate cross-network interactions, and show that
      anticorrelation between the default mode network and parietal regions of the
      dorsal attention network is consistent with an inability of the system to
      transition directly between two transient brain states. DOI:
      http://dx.doi.org/10.7554/eLife.01867.001. 

PMID- 24668170
TI  - A high-resolution morphological and ultrastructural map of anterior sensory cilia
      and glia in Caenorhabditis elegans.
AB  - Many primary sensory cilia exhibit unique architectures that are critical for
      transduction of specific sensory stimuli. Although basic ciliogenic mechanisms
      are well described, how complex ciliary structures are generated remains unclear.
      Seminal work performed several decades ago provided an initial but incomplete
      description of diverse sensory cilia morphologies in C. elegans. To begin to
      explore the mechanisms that generate these remarkably complex structures, we have
      taken advantage of advances in electron microscopy and tomography, and
      reconstructed three-dimensional structures of fifty of sixty sensory cilia in the
      C. elegans adult hermaphrodite at high resolution. We characterize novel axonemal
      microtubule organization patterns, clarify structural features at the ciliary
      base, describe new aspects of cilia-glia interactions, and identify structures
      suggesting novel mechanisms of ciliary protein trafficking. This complete
      ultrastructural description of diverse cilia in C. elegans provides the
      foundation for investigations into underlying ciliogenic pathways, as well as
      contributions of defined ciliary structures to specific neuronal functions. DOI:
      http://dx.doi.org/10.7554/eLife.01948.001. 

PMID- 24668171
TI  - CA1 cell activity sequences emerge after reorganization of network correlation
      structure during associative learning.
AB  - Animals can learn causal relationships between pairs of stimuli separated in time
      and this ability depends on the hippocampus. Such learning is believed to emerge
      from alterations in network connectivity, but large-scale connectivity is
      difficult to measure directly, especially during learning. Here, we show that
      area CA1 cells converge to time-locked firing sequences that bridge the two
      stimuli paired during training, and this phenomenon is coupled to a
      reorganization of network correlations. Using two-photon calcium imaging of mouse
      hippocampal neurons we find that co-time-tuned neurons exhibit enhanced
      spontaneous activity correlations that increase just prior to learning. While
      time-tuned cells are not spatially organized, spontaneously correlated cells do
      fall into distinct spatial clusters that change as a result of learning. We
      propose that the spatial re-organization of correlation clusters reflects global
      network connectivity changes that are responsible for the emergence of the
      sequentially-timed activity of cell-groups underlying the learned behavior. DOI:
      http://dx.doi.org/10.7554/eLife.01982.001. 

PMID- 24668172
TI  - Structure of bacterial cytoplasmic chemoreceptor arrays and implications for
      chemotactic signaling.
AB  - Most motile bacteria sense and respond to their environment through a
      transmembrane chemoreceptor array whose structure and function have been well
      studied, but many species also contain an additional cluster of chemoreceptors in
      their cytoplasm. Although the cytoplasmic cluster is essential for normal
      chemotaxis in some organisms, its structure and function remain unknown. Here we
      use electron cryotomography to image the cytoplasmic chemoreceptor cluster in
      Rhodobacter sphaeroides and Vibrio cholerae. We show that just like transmembrane
      arrays, cytoplasmic clusters contain trimers-of-receptor-dimers organized in 12
      nm hexagonal arrays. In contrast to transmembrane arrays, however, cytoplasmic
      clusters comprise two CheA/CheW baseplates sandwiching two opposed receptor
      arrays. We further show that cytoplasmic fragments of normally transmembrane E.
      coli chemoreceptors form similar sandwiched structures in the presence of
      molecular crowding agents. Together these results suggest that the 12-nm
      hexagonal architecture is fundamentally important and that sandwiching and
      crowding can replace the stabilizing effect of the membrane. DOI:
      http://dx.doi.org/10.7554/eLife.02151.001. 

PMID- 24668174
TI  - Keeping inflammation at bay.
AB  - Cells dying by apoptosis can trigger an anti-inflammatory gene response in other
      cells by releasing a compound called adenosine monophosphate. 

PMID- 24668173
TI  - Immunosuppression via adenosine receptor activation by adenosine monophosphate
      released from apoptotic cells.
AB  - Apoptosis is coupled with recruitment of macrophages for engulfment of dead
      cells, and with compensatory proliferation of neighboring cells. Yet, this death
      process is silent, and it does not cause inflammation. The molecular mechanisms
      underlying anti-inflammatory nature of the apoptotic process remains poorly
      understood. In this study, we found that the culture supernatant of apoptotic
      cells activated the macrophages to express anti-inflammatory genes such as Nr4a
      and Thbs1. A high level of AMP accumulated in the apoptotic cell supernatant in a
      Pannexin1-dependent manner. A nucleotidase inhibitor and A2a adenosine receptor
      antagonist inhibited the apoptotic supernatant-induced gene expression,
      suggesting AMP was metabolized to adenosine by an ecto-5'-nucleotidase expressed
      on macrophages, to activate the macrophage A2a adenosine receptor.
      Intraperitoneal injection of zymosan into Adora2a- or Panx1-deficient mice
      produced high, sustained levels of inflammatory mediators in the peritoneal
      lavage. These results indicated that AMP from apoptotic cells suppresses
      inflammation as a 'calm down' signal. DOI:
      http://dx.doi.org/10.7554/eLife.02172.001. 

PMID- 24668175
TI  - Tomography gives a new dimension to an ancient organelle.
AB  - Advances in sample preparation and electron microscopy have allowed the structure
      of cilia to be explored at an unprecedented level of detail. 

PMID- 24668176
TI  - Hippocampal neurons wait their turn.
AB  - Imaging large groups of neurons as mice learn to respond to an event after a time
      delay shows that the brain encodes the passage of time using ordered sequences of
      neural activity. 

PMID- 24668177
TI  - How does the brain process rhythm?
AB  - A region of the brain called the putamen has a central role in our ability to
      keep a beat in our head. 

PMID- 24668180
TI  - Surgical treatment of infantile achalasia: a case report and literature review.
AB  - Allgrove syndrome is a rare genetic disorder typically manifested by alacrima,
      achalasia, and adrenal insufficiency, and is one of the rare causes of achalasia
      in infants. While the gold standard for achalasia treatment in adults is an
      esophageal myotomy with fundoplication, a standard treatment for infantile
      achalasia remains undetermined due to the low number of reported cases and rarity
      of the disease in this age group. We report a 7.7 kg infant with achalasia
      secondary to Allgrove syndrome who was successfully treated by Heller myotomy and
      simultaneous Toupet fundoplication. This case represents one of the smallest
      patients to ever be treated for achalasia and highlights the role that primary
      surgical therapy may have for the infantile variant of the disease. 

PMID- 24668181
TI  - Complications of mechanical thrombectomy for acute ischemic stroke-a
      retrospective single-center study of 176 consecutive cases.
AB  - INTRODUCTION: There is only very limited data about complications in mechanical
      thrombectomy for acute ischemic stroke. The purpose of this study was to evaluate
      the frequency and the clinical relevance of procedure-related complications in
      mechanical thrombectomy. METHODS: We conducted a retrospective analysis of 176
      consecutive acute ischemic stroke cases that were treated with mechanical
      thrombectomy. Primary outcome measures included the following: symptomatic
      intracranial hemorrhage (sICH), vessel dissection, emboli to new vascular
      territories, vasospasm, and stent dislocation/occlusion whenever appropriate.
      Secondary outcome measures included mTICI score, time from symptom onset to
      revascularization, and time from groin puncture to revascularization as well as
      the early clinical outcome at discharge. RESULTS: Complications occurred in
      20/176 patients (11 %) comprising 23 adverse events at the following rates: sICH
      8/176 (5 %), emboli to new vascular territories 4/176 (2 %); vessel dissection
      3/176 (2 %); vasospasm of the access vessel 5/176 (3 %); stent dislocation in
      1/42 (2 %); and stent occlusion in 2/42 (5 %). Two out of 20 (10 %) suffered from
      two or more procedure-related complications. There was a statistically
      significant correlation of complications with time from groin puncture to
      revascularization, unfavorable revascularization results, and unfavorable
      clinical outcome. CONCLUSION: Overall, the frequency of procedure-related
      complications lies within acceptable limits for an emergency procedure. The
      endovascular treatment does not seem to add significantly to the stroke patients'
      risk of sICH but implies an innate risk of stroke in an initially uninvolved
      territory. Furthermore, a prolonged endovascular procedure beyond an hour is
      correlated with higher complication rates, which underlines the importance of a
      swift and complete revascularization.

PMID- 24668182
TI  - Histamine-producing bacteria in blue scad (Decapterus maruadsi) and their
      abilities to produce histamine and other biogenic amines.
AB  - Using decarboxylation medium and 16S rDNA sequence analysis, histamine-producing
      bacteria (HPB) in blue scad (Decapterus maruadsi) were isolated and identified,
      and the histamine-producing abilities of the isolated HPB were determined. Nine
      mesophilic strains (H1-H9) isolated from the muscle of blue scad were identified
      as the genera of HPB, including Arthrobacter bergeri (H1), Pseudomonas sp. (H2,
      H5 and H6), Psychrobacter sp. (H3), Shewanella baltica (H4 and H7), and Aeromonas
      salmonicida (H8 and H9), respectively. Results showed that most of the HPB
      strains were weak on histamine formation (13.0-20.4 mg/l), except for the H8
      strain with the ability of producing 115 mg of histamine/l in trypticase soy
      broth containing 1.0 % L-histidine. As the strongest HPB in blue scad, bacterial
      strain H8 also presented a strong ability to produce other biogenic amines, such
      as putrescine, cadaverine, spermidine, spermine, tyramine and tryptamine.
      Therefore, the H8 strain identified as the genus of A. salmonicida was the
      dominant mesophilic HPB strain for producing histamine and other biogenic amines
      in blue scad at room temperature.

PMID- 24668183
TI  - Hydration dependent viscoelastic tensile behavior of cornea.
AB  - The cornea is a protective transparent connective tissue covering the front of
      the eye. The standard uniaxial tensile experiments are among the most popular
      techniques for investigating biomechanical properties of the cornea. This
      experimental method characterizes the stress-strain response of corneal strips
      immersed in a bathing solution. In the present study, the important roles of
      corneal hydration on tensile viscoelastic properties were investigated. The
      thickness was used as a surrogate for hydration and uniaxial tensile experiments
      were performed on bovine corneal samples with four different average thickness
      (hydration), i.e., 1100 MUm (4.87 mg water/mg dry tissue), 900 MUm (4.13 mg
      water/mg dry tissue), 700 MUm (3.20 mg water/mg dry tissue), and 500 MUm (1.95 mg
      water/mg dry tissue). The samples were immersed in mineral oil in order to
      prevent their swelling during the experiments. A quasilinear viscoelastic (QLV)
      model was used to analyze the experimental measurements and determine
      viscoelastic material constants. It was observed that both maximum and
      equilibrium (relaxed) stresses were exponentially increased with decreasing
      tissue thickness (hydration). Furthermore, the QLV model successfully captured
      the corneal viscoelastic response with an average R (2) value greater than 0.99.
      Additional experiments were conducted in OBSS in order to confirm that these
      significant changes in viscoelastic properties were because of corneal hydration
      and not the bathing solution. The findings of this study suggest that extra care
      must be taken in interpreting the results of earlier uniaxial tensile testings
      and their correspondence to the corneal biomechanical properties.

PMID- 24668186
TI  - [Austrian Society of Hypertension].

PMID- 24668187
TI  - Variants in neuronal nitric oxide synthase gene may contribute to increased
      ischemic stroke susceptibility in a Han Chinese population.
AB  - Variants in neuronal NOS (nNOS) gene were associated with atherosclerosis and
      stroke susceptibility. We aimed to investigate the association between nNOS gene
      polymorphism and risk of ischemic stroke caused by small-artery occlusion (SAO)
      and large-artery atherosclerosis (LAA) in a Chinese population. We conducted a
      case-control study involving 381 ischemic stroke patients and 366 healthy
      subjects. Selected SNPs (rs1483757, rs2293050, and rs2139733) were genotyped and
      assessed; the association with the risk of ischemic stroke was analyzed.
      Furthermore, gender- and etiologic subtype-stratified analyses were also carried
      out to evaluate the association between nNOS polymorphisms and risk of ischemic
      stroke. No significant difference was observed between selected nNOS loci and
      risk of ischemic stroke in alleles or any genetic models in total study
      population, males or females, adjusted with age, drinking and smoking status.
      Rs2293050 and rs2139733 genotypes were associated with total cholesterol
      (rs2293050, P = 0.026; rs2139733, P = 0.040) and LDL (rs2293050, P = 0.031;
      rs2139733, P = 0.046) in females. A significant difference in allele distribution
      of rs2293050 (P = 0.040) and a marginally significant difference of rs2139733 (P
      = 0.061) in LAA-caused ischemic stroke cases and controls were observed in total
      population. No association between rs1483757 and ischemic stroke was found in
      this study. T allele of rs2293050 and A allele of rs2139733 in nNOS gene may
      contribute to increased susceptibility of LAA-caused ischemic stroke in Han
      Chinese.

PMID- 24668188
TI  - Recent trends in drug delivery system using protein nanoparticles.
AB  - Engineered nanoparticles that can facilitate drug formulation and passively
      target tumours have been under extensive research in recent years. These
      successes have driven a new wave of significant innovation in the generation of
      advanced particles. The fate and transport of diagnostic nanoparticles would
      significantly depend on nonselective drug delivery, and hence the use of high
      drug dosage is implemented. In this perspective, nanocarrier-based drug targeting
      strategies can be used which improve the selective delivery of drugs to the site
      of action, i.e. drug targeting. Pharmaceutical industries majorly focus on
      reducing the toxicity and side effects of drugs but only recently it has been
      realised that carrier systems themselves may pose risks to the patient. Proteins
      are compatible with biological systems and they are biodegradable. They offer a
      multitude of moieties for modifications to tailor drug binding, imaging or
      targeting entities. Thus, protein nanoparticles provide outstanding contributions
      as a carrier for drug delivery systems. This review summarises recent progress in
      particle-based therapeutic delivery and discusses important concepts in particle
      design and biological barriers for developing the next generation of particles
      drug delivery systems. 

PMID- 24668189
TI  - Freezing polystyrene-b-poly(2-vinylpyridine) micelle nanoparticles with different
      nanostructures and sizes.
AB  - Herein we report how to control the nanostructures and sizes of polystyrene-b
      poly(2-vinylpyridine) (PS-b-P2VP) nanoparticles via manipulating freezing in
      solvent-exchange. By characterizing and analyzing the distinct structural
      features of the obtained nanoparticles, we recognized that micelle self-assembly
      happens in the precipitation of PS-b-P2VP when water is added into the block
      copolymer (BCP) solution. Solvent properties significantly influence micelle
      types that are vesicles in acetone/H2O and spherical micelles in
      tetrahydrofuran/H2O, respectively, thus further inducing different frozen
      nanostructures of the obtained nanoparticles, onion-like in acetone/H2O and large
      compound micelles in tetrahydrofuran/H2O. By changing the concentration of the
      block copolymers and the Vsolvent/VH2O ratio to modify the freezing stage at
      which block copolymer micelles are frozen, we can further control the size of the
      nanoparticles. Moreover, small molecules (phosphotungstic acid, pyrene, 1
      pyrenebutyric acid) can be trapped into the block copolymer nanoparticles via the
      freezing process. Their distribution in the nanoparticles relies not only on the
      solvent property, but also on their interactions with block copolymers. The
      hybrid nanoparticles with ordered distribution of small molecules can be further
      changed to partially-void nanoparticles. Our study demonstrated that manipulating
      the freezing of block copolymers in the solvent exchange process is a simple and
      controllable fabrication method to generate BCP nanoparticles with different
      architectures. 

PMID- 24668192
TI  - Syntheses of a library of molecules on the marine natural product
      ianthelliformisamines platform and their biological evaluation.
AB  - Ianthelliformisamines A-C are a novel class of bromotyrosine-derived
      antibacterial agents isolated recently from the marine sponge Suberea
      ianthelliformis. We have synthesized ianthelliformisamines A-C straightforwardly
      by the condensation of (E)-3-(3,5-dibromo-4-methoxyphenyl)acrylic acid and the
      corresponding Boc-protected polyamine followed by Boc-deprotection with TFA.
      Further, using this reaction protocol, a library of their analogues (39
      analogues) has been synthesized by employing 3-phenylacrylic acid derivatives and
      Boc-protected polyamine chains through various combinations of these two
      fragments differing in phenyl ring substitution, double bond geometry or chain
      length of the central spacer of the polyamine chain (shown in red color). All the
      synthesized compounds (ianthelliformisamines A-C and their analogues) were
      screened for antibacterial activity against both Gram-negative (Escherichia coli)
      and Gram-positive (Staphylococcus aureus) strains. All synthetic analogues of
      ianthelliformisamine A showed bacterial growth inhibition against both strains
      (Escherichia coli and Staphylococcus aureus), having MIC values in the range of
      117.8-0.10 MUM, while none of the synthetic analogues of ianthelliformisamine C
      as well as the parent compound showed any detectable antibacterial activity.
      Interestingly, some of the synthetic analogues of ianthelliformisamines A and B
      exerted a bactericidal effect against both E. coli and S. aureus strains,
      decreasing viable bacterial count by 99% at concentrations as low as 2 * MIC. 

PMID- 24668190
TI  - Downregulation of GABAA receptor protein subunits alpha6, beta2, delta, epsilon,
      gamma2, theta, and rho2 in superior frontal cortex of subjects with autism.
AB  - We measured protein and mRNA levels for nine gamma-aminobutyric acid A (GABAA)
      receptor subunits in three brain regions (cerebellum, superior frontal cortex,
      and parietal cortex) in subjects with autism versus matched controls. We observed
      changes in mRNA for a number of GABAA and GABAB subunits and overall reduced
      protein expression for GABAA receptor alpha 6 (GABRalpha6), GABAA receptor beta 2
      (GABRbeta2), GABAA receptor delta (GABRdelta), GABAA receptor epsilon
      (GABRepsilon), GABAA receptor gamma 2 (GABRgamma2), GABAA receptor theta
      (GABRtheta), and GABAA receptor rho 2 (GABRrho2) in superior frontal cortex from
      subjects with autism. Our data demonstrate systematic changes in GABAA&B subunit
      expression in brains of subjects with autism, which may help explain the presence
      of cognitive abnormalities in subjects with autism. 

PMID- 24668193
TI  - Regulation of cell survival by the HIP-55 signaling network.
AB  - HIP-55 (hematopoietic progenitor kinase 1 [HPK1]-interacting protein of 55 kDa)
      is the mammalian homologue of the yeast Abp1p. It contains a C-terminal Src
      homology 3 domain and an N-terminal actin depolymerization factor (ADF-H/C)
      domain. HIP-55 appears to be critical for organ development and immune response
      and is important for the regulation of the actin cytoskeleton through its
      interactions with F-actin and various cytoskeletal and cell signaling proteins.
      However, the function of HIP-55 in tumors remains unknown. Here, we found that
      HIP-55 is up-regulated or down-regulated in several types of tumor tissues in
      patients. Of these, lung cancer tissues had the highest expression of HIP-55. To
      gain full insight into the function of HIP-55 in lung cancer, microarray assay
      was performed using Affymetrix U133 Plus 2.0 expression arrays in both HIP-55
      knockdown and scramble control A549 cells. The ingenuity pathway analysis tool
      was utilized to construct biological networks and analyze functions that might be
      associated with HIP-55. Functional analysis strongly suggested that HIP-55 may be
      involved in cancer cell survival and cell death, which was then confirmed by
      further experimentation. Experimental results showed that downregulation of HIP
      55 decreased the viability and increased the apoptosis of A549 cells treated with
      the anticancer agent etoposide. Our data suggested that HIP-55 may be a newly
      discovered regulatory node in the growth signaling network and a new target for
      therapeutic interventions in proliferative disorders. 

PMID- 24668194
TI  - The effect of oxygen tension on human articular chondrocyte matrix synthesis:
      integration of experimental and computational approaches.
AB  - Significant oxygen gradients occur within tissue engineered cartilaginous
      constructs. Although oxygen tension is an important limiting parameter in the
      development of new cartilage matrix, its precise role in matrix formation by
      chondrocytes remains controversial, primarily due to discrepancies in the
      experimental setup applied in different studies. In this study, the specific
      effects of oxygen tension on the synthesis of cartilaginous matrix by human
      articular chondrocytes were studied using a combined experimental-computational
      approach in a "scaffold-free" 3D pellet culture model. Key parameters including
      cellular oxygen uptake rate were determined experimentally and used in
      conjunction with a mathematical model to estimate oxygen tension profiles in 21
      day cartilaginous pellets. A threshold oxygen tension (pO2 ~ 8% atmospheric
      pressure) for human articular chondrocytes was estimated from these inferred
      oxygen profiles and histological analysis of pellet sections. Human articular
      chondrocytes that experienced oxygen tension below this threshold demonstrated
      enhanced proteoglycan deposition. Conversely, oxygen tension higher than the
      threshold favored collagen synthesis. This study has demonstrated a close
      relationship between oxygen tension and matrix synthesis by human articular
      chondrocytes in a "scaffold-free" 3D pellet culture model, providing valuable
      insight into the understanding and optimization of cartilage bioengineering
      approaches.

PMID- 24668195
TI  - Combined PET/MR: Where are we now? Summary report of the second international
      workshop on PET/MR imaging April 8-12, 2013, Tubingen, Germany.
AB  - This workshop was held a year after the initial positron emission
      tomography/magnetic resonance (PET/MR) workshop in Tubingen, which was recently
      reported in this journal. The discussions at the 2013 workshop, however, differed
      substantially from those of the initial workshop, attesting to the progress of
      combined PET/MR as an innovative imaging modality. Discussions were focused on
      the search for truly novel, unique clinical and research applications as well as
      technical issues such as reliable and accurate approaches for attenuation and
      scatter correction of PET emission data. The workshop provided hands-on
      experience with PET and MR imaging. In addition, structured and moderated open
      discussion sessions, including six dialogue boards and two roundtable
      discussions, provided input from current and future PET/MR imaging users. This
      summary provides a snapshot of the current achievements and challenges for
      PET/MR. 

PMID- 24668196
TI  - Dependence of outflow facility on intraocular pressure?

PMID- 24668197
TI  - Author response: Dependence of outflow facility on intraocular pressure?

PMID- 24668198
TI  - The self-esteem of adults diagnosed with attention-deficit/hyperactivity disorder
      (ADHD): a systematic review of the literature.
AB  - Individuals with attention-deficit/hyperactivity disorder (ADHD) often grow up
      with negative messages surrounding their abilities and may experience adverse
      outcomes throughout their lives. Despite this, by adulthood, those with ADHD
      often find that they are left without adequate support from services. This review
      explores the relationship between self-esteem and ADHD in adulthood with a view
      to outlining needs and potential opportunities in terms of service provision.
      Twelve databases were searched for relevant literature published between 1980 and
      2013 using terms relating to self-esteem, ADHD and adulthood. The resulting 13
      articles comprised both cross-sectional and intervention studies. Despite a
      limited number of studies and methodological concerns, there is evidence to
      suggest that ADHD is associated with lower self-esteem in adulthood and that self
      esteem difficulties can be remedied, to at least some extent, by
      psychotherapeutic work. It is recommended that future research focuses on the
      evaluation of therapy that specifically targets difficulties in self-esteem in
      this population. 

PMID- 24668199
TI  - Diabetes and the heart. From guidelines to individualized care.

PMID- 24668200
TI  - Smartphone-assisted prehospital medical information system for analyzing data on
      prehospital stroke care.
AB  - BACKGROUND AND PURPOSE: Optimizing prehospital stroke care is important because
      effective treatments for acute stroke require a narrow therapeutic time window.
      We developed a smartphone-assisted prehospital medical information system (SPMIS)
      to facilitate research on prehospital stroke care. METHODS: Prehospital medical
      information was input into the SPMIS application installed on smartphones by
      emergency medical staff, sent to a server through the Internet, and connected
      with in-hospital information. Using SPMIS, we analyzed data on 914 patients
      transferred to our institution by ambulance between April 2012 and March 2013.
      RESULTS: The data analyzed were the sensitivity and specificity of the
      prehospital diagnosis and prehospital stroke scale and the relationship between
      prehospital vital signs and forms of stroke. These analyses could be performed
      semiautomatically in a few hours. CONCLUSIONS: SPMIS enabled us to analyze the
      prehospital information of patients with stroke in a short time with little
      effort. More large-scale studies on prehospital stroke care will become feasible
      using SPMIS, which may lead to advances in stroke treatment.

PMID- 24668201
TI  - North American SOLITAIRE Stent-Retriever Acute Stroke Registry: choice of
      anesthesia and outcomes.
AB  - BACKGROUND AND PURPOSE: Previous work that predated the availability of the safer
      stent-retriever devices has suggested that general anesthesia (GA) may have a
      negative impact on outcomes in patients with acute ischemic stroke undergoing
      endovascular therapy. METHODS: We reviewed demographic, clinical, procedural (GA
      versus local anesthesia [LA], etc), and site-adjudicated angiographic and
      clinical outcomes data from consecutive patients treated with the Solitaire FR
      device in the investigator-initiated North American SOLITAIRE Stent-Retriever
      Acute Stroke (NASA) Registry. The primary outcomes were 90-day modified Rankin
      Scale, mortality, and symptomatic intracranial hemorrhage. RESULTS: A total of
      281 patients from 18 centers were enrolled. GA was used in 69.8% (196/281) of
      patients. Baseline demographic and procedural factors were comparable between the
      LA and GA groups, except the former demonstrated longer time-to-groin puncture
      (395.4+/-254 versus 337.4+/-208 min; P=0.04), lower National Institutes of Health
      Stroke Scale (NIHSS; 16.2+/-5.8 versus 18.8+/-6.9; P=0.002), lower balloon-guide
      catheter usage (22.4% versus 49.2%; P=0.0001), and longer fluoroscopy times
      (39.5+/-33 versus 28+/-22.8 min; P=0.008). Recanalization (thrombolysis in
      cerebral infarction >=2b; 72.94% versus 73.6%; P=0.9) and rate of symptomatic
      intracranial hemorrhage (7.1% versus 11.2%; P=0.4) were similar but modified
      Rankin Scale <=2 was achieved in more LA patients, 52.6% versus 35.6% (odds
      ratio, 1.4 [1.1-1.8]; P=0.01). In multivariate analysis, hypertension, NIHSS,
      unsuccessful revascularization, and GA use (odds ratio, 3.3 [1.6-7.1]; P=0.001)
      were associated with death. When only anterior circulation and elective GA
      patients were included, there was a persistent difference in good outcomes in
      favor of LA patients (50.7% versus 35.5%; odds ratio, 1.3 [1.01-1.6]; P=0.04).
      CONCLUSIONS: The NASA Registry has demonstrated that clinical outcomes and
      survival are significantly better in patients treated with LA, without increased
      symptomatic intracranial hemorrhage risk. Future trials should prospectively
      evaluate the effect of GA on outcomes.

PMID- 24668202
TI  - Multidisciplinary consensus on assessment of unruptured intracranial aneurysms:
      proposal of an international research group.
AB  - BACKGROUND AND PURPOSE: To address the increasing need to counsel patients about
      treatment indications for unruptured intracranial aneurysms (UIA), we endeavored
      to develop a consensus on assessment of UIAs among a group of specialists from
      diverse fields involved in research and treatment of UIAs. METHODS: After
      composition of the research group, a Delphi consensus was initiated to identify
      and rate all features, which may be relevant to assess UIAs and their treatment
      by using ranking scales and analysis of inter-rater agreement (IRA) for each
      factor. IRA was categorized as very high, high, moderate, or low. RESULTS:
      Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on
      the following key factors for or against UIA treatment decisions: (1) patient
      age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage
      from a different aneurysm, family history for UIA or subarachnoid hemorrhage,
      nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo
      formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass
      effect, and thromboembolic events from UIAs); and (6) risk factors for UIA
      treatment (patient age and life expectancy, UIA size, and estimated risk of
      treatment). However, IRAs for features rated with low relevance were also
      generally low, which underlined the existing controversy about the natural
      history of UIAs. CONCLUSIONS: Our results highlight that neurovascular
      specialists currently consider many features as important when evaluating UIAs
      but also highlight that the appreciation of natural history of UIAs remains
      uncertain, even within a group of highly informed individuals.

PMID- 24668203
TI  - Effects of extracranial-intracranial bypass for patients with hemorrhagic
      moyamoya disease: results of the Japan Adult Moyamoya Trial.
AB  - BACKGROUND AND PURPOSE: About one half of those who develop adult-onset moyamoya
      disease experience intracranial hemorrhage. Despite the extremely high frequency
      of rebleeding attacks and poor prognosis, measures to prevent rebleeding have not
      been established. The purpose of this study is to determine whether extracranial
      intracranial bypass can reduce incidence of rebleeding and improve patient
      prognosis. METHODS: This study was a multicentered, prospective, randomized,
      controlled trial conducted by 22 institutes in Japan. Adult patients with
      moyamoya disease who had experienced intracranial hemorrhage within the preceding
      year were given either conservative care or bilateral extracranial-intracranial
      direct bypass and were observed for 5 years. Primary and secondary end points
      were defined as all adverse events and rebleeding attacks, respectively. RESULTS:
      Eighty patients were enrolled (surgical, 42; nonsurgical, 38). Adverse events
      causing significant morbidity were observed in 6 patients in the surgical group
      (14.3%) and 13 patients in the nonsurgical group (34.2%). Kaplan-Meier survival
      analysis revealed significant differences between the 2 groups (3.2%/y versus
      8.2%/y; P=0.048). The hazard ratio of the surgical group calculated by Cox
      regression analysis was 0.391 (95% confidence interval, 0.148-1.029). Rebleeding
      attacks were observed in 5 patients in the surgical group (11.9%) and 12 in the
      nonsurgical group (31.6%), significantly different in the Kaplan-Meier survival
      analysis (2.7%/y versus 7.6%/y; P=0.042). The hazard ratio of the surgical group
      was 0.355 (95% confidence interval, 0.125-1.009). CONCLUSIONS: Although
      statistically marginal, Kaplan-Meier analysis revealed the significant difference
      between surgical and nonsurgical group, suggesting the preventive effect of
      direct bypass against rebleeding. CLINICAL TRIAL REGISTRATION URL:
      http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000166.

PMID- 24668205
TI  - Direct bypass reduces the risk of recurrent hemorrhage in moyamoya syndrome, but
      effect on functional outcome is less certain.

PMID- 24668204
TI  - Variability in outcome after elective cerebral aneurysm repair in high-volume
      academic medical centers.
AB  - BACKGROUND AND PURPOSE: Unruptured intracranial aneurysm repair is the most
      commonly performed procedure for the prevention of hemorrhagic stroke. Despite
      efforts to regionalize care in high-volume centers, overall results have improved
      little. This study aims to determine the effectiveness in improving outcomes of
      previous efforts to regionalize unruptured intracranial aneurysm repair to high
      volume centers and to recommend future steps toward that goal. METHODS: Using
      data obtained via the New York Statewide Planning and Research Cooperative
      System, this study included all patients admitted to any of the 10 highest volume
      centers in New York state between 2005 and 2010 with a principal diagnosis of
      unruptured intracranial aneurysm who were treated either by microsurgical or
      endovascular repair. Mixed-effects logistic regression was used to determine the
      degree to which hospital-level and patient-level variables contributed to
      observed variation in good outcome, defined as discharge to home, between
      hospitals. RESULTS: Of 3499 patients treated during the study period, 2692
      (76.9%) were treated at the 10 highest volume centers, with 2198 (81.6%)
      experiencing a good outcome. Good outcomes varied widely between centers, with
      44.6% to 91.1% of clipped patients and 75.4% to 92.1% of coiled patients
      discharged home. Mixed-effects logistic regression revealed that procedural
      volume accounts for 85.8% of the between-hospital variation in outcome.
      CONCLUSIONS: There is notable interhospital heterogeneity in outcomes among even
      the largest volume unruptured intracranial aneurysm referral centers. Although
      further regionalization may be needed, mandatory participation in prospective,
      adjudicated registries will be necessary to reliably identify factors associated
      with superior outcomes.

PMID- 24668206
TI  - Is MICROPERC degrees  really the new frontier of percutaneous nephrolithotripsy?

PMID- 24668207
TI  - Uncommon patterns in Nafion films loaded with silver nanoparticles.
AB  - Nafion has been frequently used for the synthesis of nanoparticles by taking
      advantage of its so-called cluster-network structure. Unexpectedly, the synthesis
      of AgNPs inside Nafion 117 was found to produce NPs organization, resulting in a
      regular pattern that could reveal the real morphology of the polymer. 

PMID- 24668209
TI  - Does complete renal denervation translate into superior clinical outcomes?
      Lessons learned from denervation of accessory renal arteries.
AB  - Pre-clinical studies of renal denervation would suggest that the extent of renal
      nerve injury correlates with outcomes. The "completeness" of renal nerve injury
      following renal denervation correlates with treatment-based variables such as the
      depth of ablation, the number of ablations along the length of the artery, and
      the number of renal arteries successfully ablated. Renal denervation techniques
      targeting only main renal arteries may lead to suboptimal results in patients
      with accessory renal artery anatomy. Technological differences among the
      different systems may make some more suited for this common anatomical variant.
      The early clinical experience with renal denervation of accessory renal arteries
      highlights the importance of complete renal denervation for clinical success. 

PMID- 24668208
TI  - The impact of vitrification on immature oocyte cell cycle and cytoskeletal
      integrity in a rat model.
AB  - PURPOSE: To test the effects of varying vitrification protocols on the cell cycle
      status and chromosomal integrity in cumulus-enclosed GV stage rat oocytes.
      METHODS: Vitrified and thawed rat oocytes were labeled with fluorescent markers
      for chromatin, cell cycle activation, and f-actin and analyzed by conventional
      and laser scanning confocal microscopy. RESULTS: In all vitrification groups,
      significant alterations in cumulus cell connectivity, cell cycle status, and
      cytoplasmic actin integrity were observed following warming compared to fresh
      control oocytes. Based on the protein phosphorylation marker MPM-2, it is clear
      that warmed oocytes rapidly enter M-phase but are unable to maintain chromosome
      integrity as a result of multiple chromatin fusions. A prominent reduction in f
      actin is evident in both the ooplasm and at the cortex of vitrified oocytes.
      Finally, an irreversible but irregular retraction of TZPs occurs on the majority
      of oocytes subjected to any of the vitrification protocols. CONCLUSIONS: These
      findings draw attention to undesirable consequences of immature oocyte
      vitrification that compromise cell cycle status and chromatin and cytoskeleton
      integrity that may not be evident until after fertilization.

PMID- 24668210
TI  - Regioisomeric allene dimer formation by the reaction of tetraarylbutatrienes with
      tetracyanoethene.
AB  - The reaction of tetraarylbutatrienes (tetraaryl[3]cumulenes) with
      tetracyanoethene (TCNE), a strong electron-accepting molecule, at room
      temperature yielded novel four-membered ring compounds (head-to-tail
      unsymmetrically substituted diarylallene dimers) by [2 + 2] cycloaddition of the
      central C=C bond of the butatrienes. This reaction proceeded through a head-to
      head symmetrically substituted diarylallene dimer intermediate. Unsymmetrical
      butatriene also formed a small amount of another head-to-tail dimer. Although the
      allene dimer is stable in nonpolar solvents, it converts to other bicyclic and
      tricyclic compounds in MeOH or CH3CN at room temperature.

PMID- 24668211
TI  - Confotronic dynamics of tubular filaments.
AB  - Tubular lattices are ubiquitous in nature and technology. Microtubules and
      nanotubes of all kinds act as important pillars of biological cells and the man
      made nano-world. We show that when prestress is introduced in such structures,
      localized conformational quasiparticles emerge and govern the collective shape
      dynamics of the lattice. When coupled via cooperative interactions these
      quasiparticles form larger-scale quasipolymer superstructures exhibiting
      collective dynamic modes and giving rise to a hallmark behavior radically
      different from semiflexible beams. 

PMID- 24668212
TI  - Improved lipid accumulation by morphology engineering of oleaginous fungus
      Mortierella isabellina.
AB  - Oleaginous fungi capable of accumulating a considerable amount of lipids are
      promising sources for lipid-based biofuel production. The specific productivities
      of filamentous fungi in submerged fermentation are often correlated with
      morphological forms. However, the relationship between morphological development
      and lipid accumulation is not known. In this study, distinct morphological forms
      of oleaginous fungus Mortierella isabellina including pellets of different sizes,
      free dispersed mycelia, and broken hyphal fragments were developed by additions
      of different concentrations of magnesium silicate microparticles. Different
      morphological forms led to different levels of lipid accumulation as well as
      different spatial patterns of lipid distribution within pellets/mycelial
      aggregates. Significant higher lipid content (0.75 g lipid/g cell biomass) and
      lipid yield (0.18 g lipid/g glucose consumed) were achieved in free dispersed
      mycelia than in pellets. Moreover, extracellular metabolite analysis showed that
      production of undesirable by-product malate was repressed in free dispersed
      mycelium form. Unveiling the desired morphological form of M. isabellina for
      lipid accumulation provided insights into molecular mechanism of lipid
      biosynthesis linked with morphological development, as well as design and
      optimization of bioprocess to produce lipid-based biofuels.

PMID- 24668213
TI  - Critical evaluation of screening questionnaires for obstructive sleep apnea in
      patients undergoing coronary artery bypass grafting and abdominal surgery.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for
      complications after surgery. However, OSA remains largely under recognized, and
      questionnaires designed to detect OSA have shown inconsistent results. Patients
      with cardiovascular diseases may not present with the typical symptoms of OSA. We
      therefore sought to compare the performance of screening questionnaires of
      patients referred for coronary artery bypass grafting (CABG) versus abdominal
      surgery (Abd surgery). METHODS: We studied 40 consecutive patients referred for
      CABG [29 men; age 56 +/- 7 years; body mass index (BMI) 30 +/- 4 kg/m(2)], and 41
      referred to Abd Surgery matched for age, gender, and BMI (28 men; age 56 +/- 8
      years; BMI 29 +/- 5 kg/m(2)). All patients were evaluated with validated
      questionnaires to predict OSA (STOP-Bang and Berlin), Epworth sleepiness scale
      (ESS) and full overnight polysomnography. RESULTS: The prevalence of OSA (apnea
      hypopnea index >=15 events/hour) in the CABG and Abd surgery groups was similar
      (52 and 41 %, respectively, p = 0.32). The Berlin questionnaire showed similar
      sensitivity (67 vs. 82 %, p = 0.17) but lower specificity in the CABG group (26
      vs. 62 %, p = 0.02). The STOP-BANG questionnaire had a high sensitivity (90 vs.
      94 %, p = 0.42) but low specificity (5 vs. 13 %, p = 0.25) in the CABG and Abd
      surgery groups, respectively. Patients referred for CABG slept less (323 [285
      376] vs. 378 [308-415] minutes, p = 0.04) but had lower levels of daytime
      sleepiness than Abd surgery patients had (ESS, 6 +/- 4 vs. 9 +/- 5; p = 0.01,
      respectively). CONCLUSIONS: Presenting clinical characteristics of OSA are
      modulated by the population evaluated and may affect the performance of screening
      questionnaires.

PMID- 24668214
TI  - Making decisions about implantable cardioverter-defibrillators from implantation
      to end of life: an integrative review of patients' perspectives.
AB  - Implantable cardioverter-defibrillators (ICDs) are used for patients at risk of
      sudden cardiac death. Patients considering ICD therapy are faced with several
      preference-sensitive decisions. Our aim was to explore patients' ICD decision
      making experiences from the decision to implant to the consideration of
      deactivation at end of life. We conducted an integrative review using Whittemore
      and Knafl's five steps. MEDLINE, CINAHL, PubMed, PsycINFO, and the Cochrane
      library were searched from 2000 to 2013. Eligible studies focused on the patient
      response regarding ICD decision-making. Key themes were identified and used as a
      framework to discuss findings through the chronological course of decisions faced
      by these patients. Of 354 potential citations, 25 articles were included. The
      trajectory of key decision points was whether or not to initiate ICD therapy,
      replace the battery, and deactivate at end of life. Three common themes from
      patients' perspectives were the influence of the patient-practitioner
      consultation on knowledge uptake, patients' decision-making preference, and their
      desire to live. Patients faced with ICD-related decisions often misunderstood the
      functionality of their ICD, or overestimated its benefit. They also expressed
      mixed preferences for the desire to be involved in decisions. The decisions
      around ICDs are particularly difficult for patients given the life and death
      trade off. Clinicians involved in the care of these patients could better support
      them by verifying their understanding and eliciting their preferences. Using a
      shared decision-making approach has the potential to achieve improved patient
      outcomes. 

PMID- 24668215
TI  - Copper-catalyzed highly efficient ester formation from carboxylic acids/esters
      and formates.
AB  - A highly efficient copper-catalyzed protocol for the synthesis of esters has been
      developed from formates. This protocol is applicable to reactions with either
      esters or acids as the substrates, and shows broad substrate scopes and high
      yields. 

PMID- 24668216
TI  - Early surgical education of residents is safe for microscopic lumbar disc
      surgery.
AB  - INTRODUCTION: It is a well-established dogma that many surgeons do not reach a
      quintessential level of their technical operative skills until successful
      completion of their training program. The aim of this study was to test the
      hypothesis that early introduction of supervised residents to non-complex spinal
      surgical procedures within a structured and supervised educational program does
      not harm the patient in terms of higher complication rates or worse pain- and
      health-related quality of life (HrQOL) outcomes. METHODS: A prospective study on
      102 patients undergoing surgery for lumbar disc herniation (LDH) was performed.
      The procedures were dichotomized into two groups according to the surgeon's level
      of experience: teaching cases (neurosurgical residents in the 1st to 4th year of
      training) and non-teaching cases (experienced board-certified faculty
      neurosurgeons). Pain levels (VAS) and the HrQOL using the 12-item short-form
      health survey (SF-12) were measured at baseline, at 4 weeks and as a survey at 1
      year postoperatively. In addition, data concerning the operation and the
      postoperative course including common complications were assessed. RESULTS:
      Intraoperative blood loss, length of surgery, as well as intra- and postoperative
      complications were similar between the study groups. Patients in both groups
      achieved equal results in terms of pain reduction after 4 weeks [mean VAS change 
      3.8 (teaching cases) vs. -3.1 (non-teaching cases), p = 0.25] and 1 year
      postoperatively [mean change in VAS -3.5 (teaching cases) vs. -3.37 (non-teaching
      cases), p = 0.84]. Teaching cases were 100 % (odds ratio of 1.00) as likely as
      non-teaching cases to achieve a favorable HrQOL response to surgery (p = 0.99).
      CONCLUSIONS: Early introduction of resident surgeons to lumbar microdiscectomy
      can be conducted safely within a structured and supervised educational program as
      it neither harms the patient nor leads to worse 1-year results. Surgical resident
      education may thus be implemented safely in times of rigorous working laws.
      However, a structured education program in which the senior surgeon gives advice,
      guidance and communicates cautions during each resident surgery is of paramount
      importance to provide high-quality patient care.

PMID- 24668218
TI  - Surface tension effects on the phase transition of a DPPC bilayer with and
      without protein: a molecular dynamics simulation.
AB  - While the surface tension of a cell membrane, or a plasma membrane, regulates
      cell functions, little is known about its effect on the conformational changes of
      the lipid bilayer and hence the resulting changes in the cell membrane. To obtain
      some insights into the phase transition of the lipid bilayer as a function of
      surface tension, we used a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)
      bilayer as a model lipid bilayer and aquaporin (AqpZ), a transmembrane channel
      protein for water, as a model embedded protein. A coarse-grained molecular
      dynamics simulation was applied to illustrate the phase transition behavior of
      the pure DPPC bilayer and aquaporin-embedded DPPC bilayer under different surface
      tensions. It was shown that an increased surface tension reduced the phase
      transition temperature of the DPPC bilayer. As for the DPPC bilayer in gel form,
      no significant changes occurred in the structure of the bilayer in response to
      the surface tension. Once in a liquid crystal state, both the structure and
      properties of the DPPC bilayer, such as area per lipid, lipid order parameters,
      bilayer thickness and lateral diffusion coefficients, were responsive to the
      magnitude of surface tension in a linear way. The presence of aquaporin
      attenuated the compact alignment of the lipid bilayer, hindered the parallel
      movement, and thus made the DPPC bilayer less sensitive to the surface tension. 

PMID- 24668219
TI  - Computational analyses reveal a prognostic impact of TULP3 as a transcriptional
      master regulator in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is recognized world-wide as an aggressive
      disease with poor prognosis in patients with or without resection. Further
      knowledge about the biological mechanisms of PDAC is necessary to enable the
      identification of novel molecular markers and therapeutic targets for early
      diagnosis and improved treatment. Transcription factors are the final effectors
      of signaling pathways and regulate a number of cellular functions. Changes in
      their expression may contribute to cellular transformation and tumor progression.
      Thus, the aim of the present study was to identify the Master Regulators (MRs) of
      transcription potentially involved in PDAC disease. To achieve this goal, we
      utilized microarray data to correlate MR genes with the tumor phenotype. Analyses
      were performed with RTN, Limma, and Survival packages in the R environment. We
      identified Tubby-like protein 3 (TULP3) as a MR of transcription in PDAC samples.
      The prognostic value of TULP3 was assessed in three independent cohort analyses.
      Our data demonstrated that pancreatic cancer patients exhibiting high
      transcriptional levels of TULP3 showed a poor overall survival rate. High
      expression levels of TULP3 may play an essential role in pancreatic cancer
      progression and possibly lead to a poor clinical outcome. Our results highlight
      the potential use of TULP3 as a clinical prognostic biomarker for pancreatic
      adenocarcinoma. 

PMID- 24668220
TI  - Pulmonary arteriovenous malformations: haemodynamics and shunt closure.

PMID- 24668221
TI  - Ranking the university stars: are opinions sufficient?

PMID- 24668222
TI  - NVVC/NHJ Durrer prizes 2013.
AB  - At the annual Spring Congress of the NVVC, the Durrer prizes were awarded to the
      authors of two of the best original/review articles published in the year 2013,
      one paper being more basically oriented and one paper being more clinically
      oriented. This annual tradition has existed since the year 2006. 

PMID- 24668223
TI  - Use of thiolated oligonucleotides as anti-fouling diluents in electrochemical
      peptide-based sensors.
AB  - We incorporated short thiolated oligonucleotides as passivating diluents in the
      fabrication of electrochemical peptide-based (E-PB) sensors, with the goal of
      creating a negatively charged layer capable of resisting non-specific adsorption
      of matrix contaminants. The E-PB HIV sensors fabricated using these diluents were
      found to be more specific and selective, while retaining attributes similar to
      the sensor fabricated without these diluents. Overall, these results highlight
      the advantages of using oligonucleotides as anti-fouling diluents in self
      assembled monolayer-based sensors. 

PMID- 24668224
TI  - Membrane flickering of the human erythrocyte: physical and chemical effectors.
AB  - Recent studies suggest a link between adenosine triphosphate (ATP) concentration
      and the amplitude of cell membrane flickering (CMF) in the human erythrocyte (red
      blood cell; RBC). Potentially, the origin of this phenomenon and the unique
      discocyte shape could be active processes that account for some of the ATP
      turnover in the RBC. Active flickering could depend on several factors, including
      pH, osmolality, enzymatic rates and metabolic fluxes. In the present work, we
      applied the data analysis described in the previous article to study time courses
      of flickering RBCs acquired using differential interference contrast light
      microscopy in the presence of selected effectors. We also recorded images of air
      bubbles in aqueous detergent solutions and oil droplets in water, both of which
      showed rapid fluctuations in image intensity, the former showing the same type of
      spectral envelope (relative frequency composition) to RBCs. We conclude that CMF
      is not directly an active process, but that ATP affects the elastic properties of
      the membrane that flickers in response to molecular bombardment in a manner that
      is described mathematically by a constrained random walk.

PMID- 24668226
TI  - Onset of antiplatelet action with high (100 mg) versus standard (60 mg) loading
      dose of prasugrel in patients with ST-segment-elevation myocardial infarction
      undergoing primary percutaneous coronary intervention: pharmacodynamic study.
AB  - BACKGROUND: In patients with ST-segment-elevation myocardial infarction
      undergoing primary percutaneous coronary intervention, a suboptimal degree of
      platelet inhibition for the first 2 hours after the standard 60 mg loading dose
      of prasugrel has been described. METHODS AND RESULTS: In a prospective, 3-center,
      nonrandomized, controlled study, 2 sequential groups of P2Y12 inhibitor-naive
      consecutive patients were loaded with either 100 mg (n=47) or 60 mg (n=35) of
      prasugrel. Platelet reactivity was assessed by VerifyNow at hours 0, 0.5, 1, 2,
      and 4. At hour 2, there was a strong trend for the primary end point of platelet
      reactivity (in P2Y12 reaction units) to be lower (least squares estimates of the
      mean difference [95% confidence interval], -45.5 [-91.2 to 0.3]; P=0.051),
      whereas platelet reactivity percentage inhibition (median, first to third
      quartile) was higher (75.5% [24%-91.8%] versus 23.5% [0%-78.3%]; P=0.02) in the
      100-mg compared with 60-mg loading dose group. At hour 2, prasugrel 100 mg over
      60 mg loading dose significantly reduced high platelet reactivity rates from
      28.6% to 8.5% (>=230 P2Y12 reaction units threshold; P=0.036) and from 31.4% to
      10.6% (>=208 P2Y12 reaction units threshold; P=0.024), whereas resulted in lower
      rate of <=20% platelet inhibition (23.4% versus 51.4%; P=0.009). CONCLUSIONS: In
      patients with ST-segment-elevation myocardial infarction treated with primary
      percutaneous coronary intervention, a higher (100 mg) than the standard loading
      dose of prasugrel results in greater and more consistent platelet inhibition, yet
      this will need to be further validated in additional studies. CLINICAL TRIAL
      REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835353.

PMID- 24668225
TI  - Intussusceptive angiogenesis: expansion and remodeling of microvascular networks.
AB  - Intussusceptive angiogenesis is a dynamic intravascular process capable of
      dramatically modifying the structure of the microcirculation. The distinctive
      structural feature of intussusceptive angiogenesis is the intussusceptive pillar-
      a cylindrical microstructure that spans the lumen of small vessels and
      capillaries. The extension of the intussusceptive pillar appears to be a
      mechanism for pruning redundant or inefficient vessels, modifying the branch
      angle of bifurcating vessels and duplicating existing vessels. Despite the
      biological importance and therapeutic potential, intussusceptive angiogenesis
      remains a mystery, in part, because it is an intravascular process that is unseen
      by conventional light microscopy. Here, we review several fundamental questions
      in the context of our current understanding of both intussusceptive and sprouting
      angiogenesis. (1) What are the physiologic signals that trigger pillar formation?
      (2) What endothelial and blood flow conditions specify pillar location? (3) How
      do pillars respond to the mechanical influence of blood flow? (4) What biological
      influences contribute to pillar extension? The answers to these questions are
      likely to provide important insights into the structure and function of
      microvascular networks.

PMID- 24668227
TI  - Intracoronary stem cell infusion after acute myocardial infarction: a meta
      analysis and update on clinical trials.
AB  - BACKGROUND: Several cell-based therapies for adjunctive treatment of acute
      myocardial infarction have been investigated in multiple clinical trials, but the
      benefits still remain controversial. This meta-analysis aims to evaluate the
      efficacy of bone marrow-derived mononuclear cell (BMMNC) therapy in patients with
      acute myocardial infarction, but also explores the effect of newer generations of
      stem cells. METHODS AND RESULTS: A random-effects meta-analysis was performed on
      randomized controlled trials investigating the effects of stem cell therapy in
      patients with acute myocardial infarction that were published between January
      2002 and September 2013. The defined end points were left ventricular (LV)
      ejection fraction, LV end-systolic and end-diastolic volumes, infarct size, and
      major adverse cardiac and cerebrovascular event rates. Also, several subgroup
      analyses were performed on BMMNC trials. Overall, combining the results of 22
      randomized controlled trials (RCTs), LV ejection fraction increased by +2.10%
      (95% confidence interval [CI], 0.68-3.52; P=0.004) in the BMMNC group as compared
      with controls, evoked by a preservation of LV end-systolic volume (-4.05 mL; 95%
      CI, -6.91 to -1.18; P=0.006) and a reduction in infarct size (-2.69%; 95% CI, 
      4.83 to -0.56; P=0.01). However, there is no effect on cardiac function, volumes,
      or infarct size, when only RCTs (n=9) that used MRI-derived end points were
      analyzed. Moreover, no beneficial effect could be detected on major adverse
      cardiac and cerebrovascular event rates after BMMNC infusion after a median
      follow-up duration of 6 months. CONCLUSIONS: Intracoronary infusion of BMMNC is
      safe, but does not enhance cardiac function on MRI-derived parameters, nor does
      it improve clinical outcome. New and possibly more potent stem cells are emerging
      in the field, but their clinical efficacy still needs to be defined in future
      trials.

PMID- 24668231
TI  - High activity of cubic PtRh alloys supported on graphene towards ethanol
      electrooxidation.
AB  - Cubic PtRh alloys supported on graphene (PtxRhy/GN) with different atomic ratio
      of Pt and Rh were directly synthesized for the first time using the modified
      polyol method with Br(-) for the shape-directing agents. The process didn't use
      surface-capping agents such as PVP that easily occupy the active sites of
      electrocatalysts and are difficult to remove. Graphene is the key factor for
      cubic shape besides Br(-) and keeping catalysts high-dispersed. The X-ray
      diffraction (XRD), scanning electron microscope (SEM) and transmission electron
      microscope (TEM) were used to characterize the structure and morphology of these
      electrocatalysts. The results showed that they were composed of homogeneous cubic
      PtRh alloys. Traditional electrochemical methods, such as cyclic voltammetry and
      chronoamperometry, were used to investigate the electrocatalytic properties of
      PtxRhy/GN towards ethanol electrooxidation. It can be seen that PtxRhy/GN with
      all atomic ratios exhibited high catalytic activity, and the most active one has
      a composition with Pt : Rh = 9 : 1 atomic ratio. Electrochemical in situ FTIR
      spectroscopy was used to evaluate the cleavage of C-C bond in ethanol at room
      temperature in acidic solutions, the results illustrated that Rh in an alloy can
      promote the split of C-C bond in ethanol, and the alloy catalyst with atomic
      ratio Pt : Rh = 1 : 1 showed obviously better performance for the C-C bond
      breaking in ethanol and higher selectivity for the enhanced activity of ethanol
      complete oxidation to CO2 than alloys with other ratios of Pt and Rh. The
      investigation indicates that high activity of PtxRhy/GN electrocatalyst towards
      ethanol oxidation is due to the specific shape of alloys and the synergistic
      effect of two metal elements as well as graphene support.

PMID- 24668230
TI  - Recent progress in the development of fluorometric and colorimetric chemosensors
      for detection of cyanide ions.
AB  - The presence of cyanide ions in surface water is not only caused by industrial
      waste but also by biological processes. Owing to the extreme toxicity of cyanide
      in physiological systems and its widespread presence in the environment,
      considerable attention has been given to the development of methods for the
      detection of cyanide. Among the most simple, inexpensive and rapid methods to
      detect cyanide ions are chemosensors that rely on fluorometric and colorimetric
      responses. This review, which focuses on CN(-) fluorescence and colorimetric
      chemosensors that have been developed since 2010, follows a format in which the
      sensors are classified according to their structural features and reaction
      mechanisms. Finally, a general overview of the design of fluorometric and
      colorimetric chemosensors for CN(-) is provided. 

PMID- 24668232
TI  - Spatiotemporal stress and structure evolution in dynamically sheared polymer-like
      micellar solutions.
AB  - The complex, nonlinear flow behavior of soft materials transcends industrial
      applications, smart material design and non-equilibrium thermodynamics. A long
      standing, fundamental challenge in soft-matter science is establishing a
      quantitative connection between the deformation field, local microstructure and
      macroscopic dynamic flow properties i.e., the rheology. Here, a new experimental
      method is developed using simultaneous small angle neutron scattering (SANS) and
      nonlinear oscillatory shear rheometry to investigate the spatiotemporal
      microstructure evolution of a polymer-like micellar (PLM) solution. We
      demonstrate the novelty of nonlinear oscillatory shear experimental methods to
      create and interrogate metastable material states. These include a precursory
      state to the shear banded condition as well as a disentangled, low viscosity
      state with an inhomogeneous supra-molecular microstructure flowing at high shear
      rates. This new experimental evidence provides insight into the complexities of
      the shear banding phenomenon often observed in sheared complex fluids and
      provides valuable data for quantitatively testing non-equilibrium theory. 

PMID- 24668228
TI  - Role of receptor binding specificity in influenza A virus transmission and
      pathogenesis.
AB  - The recent emergence of a novel avian A/H7N9 influenza virus in poultry and
      humans in China, as well as laboratory studies on adaptation and transmission of
      avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation
      to mammals. One of the biological traits required for animal influenza viruses to
      cross the species barrier that received considerable attention in animal model
      studies, in vitro assays, and structural analyses is receptor binding
      specificity. Sialylated glycans present on the apical surface of host cells can
      function as receptors for the influenza virus hemagglutinin (HA) protein. Avian
      and human influenza viruses typically have a different sialic acid (SA)-binding
      preference and only few amino acid changes in the HA protein can cause a switch
      from avian to human receptor specificity. Recent experiments using glycan arrays,
      virus histochemistry, animal models, and structural analyses of HA have added a
      wealth of knowledge on receptor binding specificity. Here, we review recent data
      on the interaction between influenza virus HA and SA receptors of the host, and
      the impact on virus host range, pathogenesis, and transmission. Remaining
      challenges and future research priorities are also discussed. 

PMID- 24668233
TI  - Silver and platinum-catalysed addition of O-H and N-H bonds to allenes.
AB  - Transition-metal catalysed nucleophile addition to allenes is a very powerful
      tool for the synthesis of functionalised molecules containing heteroatoms,
      heterocycles in the intramolecular version, or allyl derivatives in the
      intermolecular version. The reaction has been explored with a wide variety of
      metals, silver being one of the most effective. Although platinum has somehow
      been less explored, different reactivities have been observed with this metal,
      showing the great potential and versatility of this methodology. This review will
      highlight the reactions with these two metals, silver and platinum, when oxygen
      or nitrogen nucleophiles are employed. Although most of the examples describe the
      intramolecular version, some intermolecular reactions with platinum have been
      described, and will also be covered. 

PMID- 24668229
TI  - Traffic into silence: endomembranes and post-transcriptional RNA silencing.
AB  - microRNAs (miRNAs) and small interfering RNAs (siRNAs) are small RNAs that
      repress gene expression at the post-transcriptional level in plants and animals.
      Small RNAs guide Argonaute-containing RNA-induced silencing complexes to target
      RNAs in a sequence-specific manner, resulting in mRNA deadenylation followed by
      exonucleolytic decay, mRNA endonucleolytic cleavage, or translational inhibition.
      Although our knowledge of small RNA biogenesis, turnover, and mechanisms of
      action has dramatically expanded in the past decade, the subcellular location of
      small RNA-mediated RNA silencing still needs to be defined. In contrast to the
      prevalent presumption that RNA silencing occurs in the cytosol, emerging evidence
      reveals connections between the endomembrane system and small RNA activities in
      plants and animals. Here, we summarize the work that uncovered this link between
      small RNAs and endomembrane compartments and present an overview of the
      involvement of the endomembrane system in various aspects of RNA silencing. We
      propose that the endomembrane system is an integral component of RNA silencing
      that has been long overlooked and predict that a marriage between cell biology
      and RNA biology holds the key to a full understanding of post-transcriptional
      gene regulation by small RNAs. 

PMID- 24668234
TI  - Postnatal development of fetuses with a single umbilical artery: differences
      between malformed and non-malformed infants.
AB  - BACKGROUND: The presence of a single umbilical artery (SUA) is a fetal soft
      marker of congenital abnormalities. Among the most common related malformations,
      there are cardiological, nephrourological and digestive anomalies, most of which
      are considered to have a vascular etiology. There is an association between
      increased incidence of intrauterine growth retardation and adverse perinatal
      indicators, but whether this association is due to related anomalies or isolated
      SUA (iSUA) is controvisal. METHODS: We reviewed 96 cases of iSUA and non-isolated
      SUA (niSUA), diagnosed in a period of two years in a referral hospital for high
      risk pregnancies. Data on prenatal explorations, including fetal ultrasonography
      and karyotyping, were obtained. niSUA was diagnosed when no malformations were
      found prenatally or in postnatal evaluation. RESULTS: Sixty-six newborns (68.8%)
      had no other anomalies and 30 (31.3%) presented with a variety of malformations
      including heart diseases, urophaties, digestive, nervous and musculoskeletal
      disorders, genetic abnormalities and complex malformations. Cardiological and
      nephrourological abnormalities were found to be the most frequent association
      with a SUA (both in 23.8% of malformed SUA newborns). Intrauterine growth
      restriction was not higher in iSUA newborns than in a normal population.
      Ultrasound allowed optimal prenatal diagnosis in most cases. CONCLUSIONS: The
      prognosis of the fetus with a SUA is determined by the presence of other
      malformations observed by an expert sonographer. If no other findings are made,
      only a routine physical examination should be performed in newborns, but no other
      complementary examinations are required.

PMID- 24668236
TI  - Reconstruction of a new pulmonary artery in arterial switch operation.
AB  - BACKGROUND: This study was undertaken to evaluate the new method for the
      reconstruction of the pulmonary artery in arterial switch operation (ASO).
      METHODS: A total of 108 consecutive infants with congenital heart disease were
      treated with ASO in our department between January 2004 and June 2012. The new
      pulmonary arterial root was reconstructed with a fresh autologuos pericardium
      which was clipped pants-like with continuous mattress suture of 6-0 Prolene
      thread. Patients were reexamined consecutively at 3 and 6 months and 1, 2 and 6
      years after discharge. The pulmonary arterial blood velocity was measured by
      continuous Doppler during systole. The pulmonary flow of healthy children of same
      age was also measured in the control group. Simplified Bernoulli formula was used
      to calculate the pressure gradient via the pulmonary artery for determining
      whether there was pulmonary stenosis. RESULTS: In this series, 96 infants
      survived after the surgery and 88 were followed up with a mean peirod of (22+/-4)
      months. No pulmonary stenosis was detected with the simplified Bernoulli formula.
      CONCLUSION: No pulmonary stenosis was detected with the simplified Bernoulli
      formula.

PMID- 24668235
TI  - Declining age of puberty of school girls in southern Thailand.
AB  - BACKGROUND: Declines in the onset age of secondary sexual development have been
      reported in a number of recent studies in western and Asian countries. A study of
      Hat-Yai school girls in 1994 in Thailand showed that the ages at thelarche and
      menarche were 9.9 and 12.4 years, respectively. This study was to determine
      whether there was a decline in the average age of puberty in Hat-Yai school girls
      from 1994 to 2012. METHODS: A cross-sectional study was conducted in 2140 healthy
      Hat-Yai school girls, aged 6-18 years, from June 2011 to March 2012. Breast and
      pubic hair development was assessed by the Tanner staging method. Probit analysis
      was used to calculate the median ages of different stages of breast and pubic
      hair development, and the age of menarche. RESULTS: The median ages of girls
      having thelarche and menarche were 9.6 (95% CI, 9.4-9.8) and 12.2 (95% CI, 11.9
      12.4) years, which declined from 9.9 (95% CI, 9.7-10.1) and 12.4 years (95% CI,
      12.2-12.6) in the 1994 study respectively, however, without statistical
      significance. The youngest ages of girls who had breast stage 2 and menarche were
      7.2 and 9.2 years, respectively. The final height at age 14 years in this cohort
      (157.3 cm) was 2.3 cm greater than that of girls in 1994 (155.0 cm). CONCLUSIONS:
      From 1994 to 2012, the age at onset of thelarche and menarche of girls in Hat-Yai
      municipality declined by 0.2 and 0.3 years, respectively. The earlier age at
      onset of puberty had no effect on final adult height.

PMID- 24668237
TI  - Timely recognition of Amyand's hernia with appendicitis in infants.
AB  - BACKGROUND: Amyand's hernia with acute appendicitis is rare in infants and is
      mostly delayed in diagnosis and treatment, resulting in a high morbidity.
      METHODS: We presented two cases of infantile Amyand's hernia with acute
      appendicitis. RESULTS: Early surgical interventions were performed and both
      patients recovered without complication. CONCLUSION: A practical strategy for
      this entity is to be aware of the rare disease and to perform early surgical
      exploration for suspected cases.

PMID- 24668238
TI  - Lemierre's syndrome with double heterozygote status in the
      methylenetetrahydrofolate reductase gene.
AB  - BACKGROUND: There are some risk factors being more vulnerable to Lemierre's
      syndrome such as a hypercoagulable state. METHODS: We report a rare case of
      Lemierre's syndrome with ethmoid and maxillary sinusitis, bilateral mastoiditis,
      and sigmoid sinus thrombosis. RESULTS: Genetic study revealed a double
      heterozygote status in the methylenetetrahydrofolate reductase gene including
      C677T and A1298C. CONCLUSION: It is suggested to screen patients with Lemierre's
      syndrome for a hypercoagulable state to consider anticoagulant therapy.

PMID- 24668239
TI  - Thyroid peroxidase antibody positivity and triiodothyronine levels are associated
      with pediatric Graves' ophthalmopathy.
AB  - BACKGROUND: Graves' ophthalmopathy (GO) occurs commonly in children with Graves'
      disease (GD). However, there are limited studies on the clinical manifestations
      and thyroid autoantibodies in pediatric GO. The aim of this study was to
      investigate the prevalence and risk factors of GO in childhood GD. METHODS:
      Clinical and biochemical data from children and adolescents with GD were
      retrospectively reviewed. Eighty patients under 19 years of age were included in
      the present study. We compared the clinical and biochemical differences between
      patients with and without GO. RESULTS: Thirty-nine percent of the patients had
      GO, and 81% of the GO patients were females. Of these, two patients showed
      unilateral GO. Triiodothyronine (T3) levels were higher in GO patients than in
      those without GO. Anti-thyroglobulin antibody and thyroid stimulating hormone
      receptor antibody titers were not significantly different between the two groups.
      Anti-thyroid peroxidase antibody (TPO Ab) positivity was 68% in the patients with
      GO and only 47% in the patients without GO. In multivariate regression analysis,
      high T3 levels and TPO Ab positivity were related to the presence of GO.
      CONCLUSION: In children and adolescents with GD, TPO Ab positivity and high T3
      levels could act as predictive factors for the presence of GO.

PMID- 24668240
TI  - Zonisamide: a review of its use as adjunctive therapy in the management of
      partial seizures in pediatric patients aged >=6 years.
AB  - Oral zonisamide (Zonegran(r)) is a benzisoxazole derivative chemically unrelated
      to other antiepileptic drugs (AEDs). It is approved in the EU as an adjunct to
      other AEDs in the treatment of pediatric patients aged >=6 years with partial
      seizures, with or without secondary generalization. In a randomized, double
      blind, multinational, phase III study in pediatric patients aged 6-17 years with
      partial seizures, the proportion of patients achieving a >=50 % reduction from
      baseline in seizure frequency per 28 days during the maintenance treatment period
      was significantly higher with adjunctive therapy with zonisamide than placebo.
      The antiepileptic efficacy of zonisamide was sustained during a 59-week extension
      study in this patient population. Zonisamide was generally well tolerated in
      these studies, with the majority of adverse events being mild or moderate in
      severity. Thus, oral zonisamide as an adjunctive therapy to other AEDs provides a
      useful option in the treatment of pediatric patients aged >=6 years with partial
      seizures.

PMID- 24668241
TI  - The role of linear and voltage-dependent ionic currents in the generation of slow
      wave oscillations.
AB  - Neuronal oscillatory activity is generated by a combination of ionic currents,
      including at least one inward regenerative current that brings the cell towards
      depolarized voltages and one outward current that repolarizes the cell. Such
      currents have traditionally been assumed to require voltage-dependence. Here we
      test the hypothesis that the voltage dependence of the regenerative inward
      current is not necessary for generating oscillations. Instead, a current I NL
      that is linear in the biological voltage range and has negative conductance is
      sufficient to produce regenerative activity. The current I NL can be considered a
      linear approximation to the negative-conductance region of the current-voltage
      relationship of a regenerative inward current. Using a simple conductance-based
      model, we show that I NL , in conjunction with a voltage-gated, non-inactivating
      outward current, can generate oscillatory activity. We use phase-plane and
      bifurcation analyses to uncover a rich variety of behaviors as the conductance of
      I NL is varied, and show that oscillations emerge as a result of destabilization
      of the resting state of the model neuron. The model shows the need for well
      defined relationships between the inward and outward current conductances, as
      well as their reversal potentials, in order to produce stable oscillatory
      activity. Our analysis predicts that a hyperpolarization-activated inward current
      can play a role in stabilizing oscillatory activity by preventing swings to very
      negative voltages, which is consistent with what is recorded in biological
      neurons in general. We confirm this prediction of the model experimentally in
      neurons from the crab stomatogastric ganglion. 

PMID- 24668242
TI  - Synthesis of a multibranched porphyrin-oligonucleotide scaffold for the
      construction of DNA-based nano-architectures.
AB  - The interest in the functionalization of oligonucleotides with organic molecules
      has grown considerably over the last decade. In this work, we report on the
      synthesis and characterization of porphyrin-oligonucleotide hybrids containing
      one to four DNA strands (P1-P4). The hybrid P4, which inserts one porphyrin and
      four DNA fragments, was combined with gold nanoparticles and imaged by
      transmission electron microscopy. 

PMID- 24668243
TI  - On a novel mechanistic model for simultaneous enzymatic hydrolysis of cellulose
      and hemicellulose considering morphology.
AB  - We develop a novel and general modeling framework for enzymatic hydrolysis of
      cellulose and hemicellulose simultaneously. Our mechanistic model, for the first
      time, takes into consideration explicitly the time evolution of morphologies of
      intertwining cellulose and hemicelluloses within substrate during enzymatic
      hydrolysis. This morphology evolution is driven by hydrolytic chain fragmentation
      and solubilization, which is, in return, profoundly affected by the substrate
      morphology. We represent the substrate morphology as a randomly distributed
      smallest accessible compartments (SACs) which are described by geometric
      functions to track total volume and exposed surface substrate materials,
      including both cellulose and hemicelluloses. Our morphology-plus-kinetics
      approach then couple the time-dependent morphology with chain fragmentation and
      solubilization resulted from enzymatic reactions between various bonds in
      cellulose and hemicelluloses and a mixture (i.e., endo-, exo-, and oligomer-
      acting) of cellulases and hemicellulases. In addition, we propose an advanced and
      generalized site concentration formalism that considers different polysaccharide
      chain types and different monomer unit types on chains. The resulting ODE system
      has a substantially reduced size compared to conventional chain concentration
      formalism. We present numerical simulation results under real enzymatic
      hydrolysis experimental conditions from literature. The comparisons between the
      simulation results and the experiment measurements demonstrate effectiveness and
      wide applicability of the proposed mechanistic model.

PMID- 24668245
TI  - Role of primary substrate composition on microbial community structure and
      function and trace organic chemical attenuation in managed aquifer recharge
      systems.
AB  - This study was performed to reveal the microbial community characteristics in
      simulated managed aquifer recharge (MAR), a natural water treatment system, under
      different concentrations and compositions of biodegradable dissolved organic
      carbon (BDOC) and further link these to the biotransformation of emerging trace
      organic chemicals (TOrCs). Two pairs of soil-column setups were established in
      the laboratory receiving synthetic feed solutions composed of different
      peptone/humic acid ratios and concentrations. Higher BDOC concentration resulted
      in lower microbial community diversity and higher relative abundance of
      Betaproteobacteria. Decreasing the peptone/humic acid ratio resulted in higher
      diversity of the community and higher relative abundances of Firmicutes,
      Planctomycetes, and Actinobacteria. The metabolic capabilities of microbiome
      involved in xenobiotics biodegradation were significantly promoted under lower
      BDOC concentration and higher humic acid content. Cytochrome P450 genes were also
      more abundant under these primary substrate conditions. Lower peptone/humic acid
      ratios also promoted the attenuation of most TOrCs. These results suggest that
      the primary substrate characterized by a more refractory character could increase
      the relative abundances of Firmicutes, Planctomycetes, and Actinobacteria, as
      well as associated cytochrome P450 genes, all of which should play important
      roles in the biotransformation of TOrCs in this natural treatment system. 

PMID- 24668244
TI  - Engineering of Corynebacterium glutamicum for growth and L-lysine and lycopene
      production from N-acetyl-glucosamine.
AB  - Sustainable supply of feedstock has become a key issue in process development in
      microbial biotechnology. The workhorse of industrial amino acid production
      Corynebacterium glutamicum has been engineered towards utilization of alternative
      carbon sources. Utilization of the chitin-derived aminosugar N-acetyl-glucosamine
      (GlcNAc) for both cultivation and production with C. glutamicum has hitherto not
      been investigated. Albeit this organism harbors the enzymes N-acetylglucosamine-6
      phosphatedeacetylase and glucosamine-6P deaminase of GlcNAc metabolism (encoded
      by nagA and nagB, respectively) growth of C. glutamicum with GlcNAc as substrate
      was not observed. This was attributed to the lack of a functional system for
      GlcNAc uptake. Of the 17 type strains of the genus Corynebacterium tested here
      for their ability to grow with GlcNAc, only Corynebacterium glycinophilum
      DSM45794 was able to utilize this substrate. Complementation studies with a
      GlcNAc-uptake deficient Escherichia coli strain revealed that C. glycinophilum
      possesses a nagE-encoded EII permease for GlcNAc uptake. Heterologous expression
      of the C. glycinophilum nagE in C. glutamicum indeed enabled uptake of GlcNAc.
      For efficient GlcNac utilization in C. glutamicum, improved expression of nagE
      with concurrent overexpression of the endogenous nagA and nagB genes was found to
      be necessary. Based on this strategy, C. glutamicum strains for the efficient
      production of the amino acid L-lysine as well as the carotenoid lycopene from
      GlcNAc as sole substrate were constructed.

PMID- 24668246
TI  - A thermophilic endo-1,4-beta-glucanase from Talaromyces emersonii CBS394.64 with
      broad substrate specificity and great application potentials.
AB  - Thermophilic cellulases are of significant interest to the efficient conversion
      of plant cell wall polysaccharides into simple sugars. In this study, a
      thermophilic and thermostable endo-1,4-beta-glucanase, TeEgl5A, was identified in
      the thermophilic fungus Talaromyces emersonii CBS394.64 and functionally
      expressed in Pichia pastoris. Purified recombinant TeEgl5A exhibits optimal
      activity at pH 4.5 and 90  degrees C. It is highly stable at 70  degrees C and
      over a broad pH range of 1.0-10.0, and shows strong resistance to most metal
      ions, sodium dodecyl sulfate (SDS), and proteases. TeEgl5A has broad substrate
      specificity and exhibits high activity on substrates containing beta-1,4
      glycosidic bonds and beta-1,3-glycosidic bonds (barley beta-glucan, laminarin,
      lichenan, CMC-Na, carob bean gum, and birchwood xylan). Under simulated mashing
      conditions, addition of 60 U TeEgl5A reduced more viscosity (10.0 vs.7.6 %) than
      80 U of Ultraflo XL from Novozymes. These properties make TeEgl5A a good
      candidate for extensive application in the detergent, textile, feed, and food
      industries. 

PMID- 24668247
TI  - Nocturnal manifestations of atypical and vascular parkinsonism: how do they
      differ from Parkinson's disease?
AB  - While nocturnal disturbances of Parkinson's disease (PD) are increasingly
      recognized as being part of a continuum that includes daytime manifestations,
      there is still little analysis in the medical literature that assesses these
      complex phenomena in patients with atypical (AP) and vascular parkinsonisms (VP).
      The objective of our study was to determine the prevalence of these disturbances
      in patients with AP and VP and to determine the range of nighttime symptoms that
      occur compared with those in patients with PD. This comparison was done using a
      semi-structured interview and self-rated questionnaires in 63 AP and VP patients
      (PSP 24, MSA 24, CBD 5, and VP 10), and 208 PD patients. 61 AP and VP patients
      (96.8%) and 201 PD patients (96.6%) reported at least one nocturnal symptom with
      a score of less than 6 on the Modified Parkinson's Disease Sleep Scale (MPDSS).
      Nocturnal akinesia, as measured on the Nocturnal Akinesia, Dystonia, and Cramp
      Score, was found to be significantly greater in patients with PSP (p = 0.006),
      MSA (p = 0.002), and CBD (p = 0.012) than PD patients, but not VP patients (p =
      0.428). Like those with PD, patients with AP and VP identified the problem of
      getting up at night to urinate (MPDSS item 8) as being the most frequent and
      troublesome nocturnal symptom. MSA and PSP patients reported more frequent (p =
      0.001) and troublesome (p < 0.001) urinary incontinence (MPDSS item 9) than PD
      patients and MSA patients had more severe problems with unexpectedly falling
      asleep during the day (MPDSS item 15) than PD patients (p = 0.003). In summary,
      our study determined that nocturnal manifestations are commonly experienced by
      patients with AP and VP and highlighted specific nocturnal symptoms, which are
      more prevalent and troublesome in certain AP syndromes. The concept of 24-h
      control of symptoms should not be limited to only PD and we recommend that all
      who are involved in the care of AP and VP patients should realize that many
      nocturnal symptoms are experienced by these patients and a multidisciplinary
      approach should be utilized to address these problems.

PMID- 24668248
TI  - Potassium-selective optical microsensors based on surface modified polystyrene
      microspheres.
AB  - Ion-selective microspheres based on surface modification of polystyrene particles
      (0.8 and 2.4 MUm, diameter) are presented here for the first time. The
      traditional lipophilic sensing components of K(+) selective optodes
      (chromoionophore, ion-exchanger and ionophore) are adsorbed on the surface of the
      polystyrene particles using a simple mixed solvent method. The resulting
      microparticles respond to K(+) in an exhaustive sensing mode with excellent
      selectivity and rapid response time (t95% = 5 s). 

PMID- 24668249
TI  - Oxidative injury and antioxidant genes regulation in cadmium-exposed radicles of
      six contrasted Medicago truncatula genotypes.
AB  - Oxidative disorders were triggered in the presence of Cd toxicity in early
      seedling growth of six Medicago truncatula genotypes. Interactions between root
      growth inhibition, cadmium uptake, as well as the occurrence of oxidative injury
      suggest differential responses of the genotypes, with susceptible or tolerant
      accessions. ROS enhancement was observed in situ and H2O2 content was measured,
      that did not seem related to tolerance or susceptibility. Oxidative burst impact
      on cell membrane integrity was analyzed in agreement with MDA content and glucose
      exudation, which suggest an active role of this burst in susceptible lines.
      Transcriptional changes in response to cadmium treatment were analyzed on target
      genes involved in (1) ROS-scavenging enzymes (superoxide dismutase (SOD;
      EC1.15.1.1) and peroxidase (PRX; EC 1.11.1.7)), (2) reduced glutathione (gamma
      Glu-Cys-Gly, GSH) metabolism (glutathione-S-transferase (GST; EC: 2.5.1.18) and
      glutathione reductase (GR; EC 1.8.1.7)), and (3) metal-chelating metabolism
      (PCS). The susceptible line shows no response or non-timely gene expression
      patterns. This research work gave an overview of the deleterious effects and
      oxidative injury of cadmium stress in Medicago truncatula. Oxidative defense
      efficiency and gene upregulation should explain relative tolerance in tested
      genotypes.

PMID- 24668250
TI  - Radiotherapy for benign calcaneodynia: long-term results of the Erlangen Dose
      Optimization (EDO) trial.
AB  - BACKGROUND AND PURPOSE: The goal of this work was to evaluate the long-term
      efficacy of two dose-fractionation schedules for radiotherapy of calcaneodynia.
      PATIENTS AND METHODS: Between February 2006 and February 2010, 457 evaluable
      patients were recruited for this prospective trial. All patients received
      orthovoltage radiotherapy. One course consisted of 6 fractions/3 weeks. In case
      of insufficient remission of pain after 6 weeks a second series was performed.
      Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy.
      Endpoint was pain reduction. Pain was measured before, right after (early
      response), 6 weeks (delayed response), and approximately 2.5 years after
      radiotherapy (long-term response) with a questionnaire-based visual analogue
      scale (VAS) and a comprehensive pain score (CPS). RESULTS: The median follow-up
      was 32 months (range 9-57 months). The overall early, delayed, and long-term
      response rates for all patients were 87, 88, and 95%. The mean VAS values before
      treatment, for early, delayed, and long-term response for the 0.5 and 1.0 Gy
      groups were 65.5 +/- 22.1 and 64.0 +/- 20.5 (p = 0.19), 34.8 +/- 24.7 and 39.0 +/
      26.3 (p = 0.12), 25.1 +/- 26.8 and 28.9 +/- 26.8 (p = 0.16), and 16.3 +/- 24.3
      and 14.1 +/- 19.7 (p = 0.68). The mean CPS values before treatment, for early,
      delayed, and log-term response were 10.1 +/- 2.7 and 10.0 +/- 3.0 (p = 0.78), 5.6
      +/- 3.7 and 6.0 +/- 3.9 (p = 0.34), 4.0 +/- 4.1 and 4.3 +/- 3.6 (p = 0.26), and
      2.1 +/- 3.3 and 2.3 +/- 3.2 (p = 0.34), respectively. No significant differences
      in long-term response quality between the two arms were found (p = 0.50).
      CONCLUSION: Radiotherapy is a very effective treatment for the management of
      benign calcaneodynia. For radiation protection reasons, the dose for a RT series
      should not exceed 3.0 Gy.

PMID- 24668251
TI  - Parvovirus b19 persistence in abnormal thyroid tissue of a mature cystic ovarian
      teratoma: a case report.
AB  - Ovarian teratomas represent the most common neoplasm derived from germ cells and
      can contain mature ectodermal, mesodermal, and endodermal tissues. In rare cases,
      these teratomas can be composed predominantly or solely of thyroid tissue. These
      thyroid cells often function similarly to normal thyroid tissues. This laboratory
      and others have previously shown that parvovirus B19 (B19V) persists in primary
      and metastatic thyroid tissues. No reports exist on possible B19V persistence in
      thyroid tissues that may arise de novo outside the thyroid gland proper. In this
      case report, the detection of B19V (genotype 1) in the thyroid epithelial cells
      of a mature teratoma is reported. Nested PCR and immunohistochemistry were used
      to detect viral nucleic acids and proteins, respectively. Viral genomes were
      amplified in lesion DNA, confirming persistence of B19V. Positive
      immunohistochemical staining was seen for B19V capsid proteins in the thyroid
      epithelial cells within the mature teratoma, but not in surrounding ovarian
      tissue or in the non-thyroidal elements of the mature teratoma. These results
      demonstrate for the first time that thyroid epithelial cells, derived from non
      thyroid tissue, are capable of supporting B19V infection and persistence. 

PMID- 24668252
TI  - Comparison of fetal outcome in premature vaginal or cesarean breech delivery at
      24-37 gestational weeks.
AB  - PURPOSE: To compare the fetal outcome of preterm breech infants delivered
      vaginally (VD) or by cesarean section (CS). METHODS: A monocentric, retrospective
      consecutive case series of preterm breech deliveries between 24-37 gestational
      weeks over 10 years from 1/2000 to 12/2009 was performed in a perinatal care
      center (Level 1) at the University Clinic of Salzburg, Austria. Data from
      hospital database were statistically analyzed and compared regarding birth
      weight, head circumference, parity, transfer rate to neonatal intensive care unit
      (NICU), arterial and venous cord blood pH and base excess (BE), arterial cord
      blood pH <= 7.10 and BE <= -11. Special focus was on fetal outcome of elective CS
      preterm breech deliveries with a non-urgent medical indication compared to VD.
      RESULTS: Among 22.115 deliveries, there were 346 live-born preterm singletons and
      twins in breech presentation (1.56 %), born between 24 + 0 and 37 + 0 gestational
      weeks. 180 CS and 36 vaginally delivered preterm breech infants were
      statistically evaluated. On comparing CS vs. VD for premature breech singletons,
      arterial cord blood pH and BE were lower in the VD group. VD twins had a lower
      arterial cord blood pH than CS twins. All other parameters were comparable. In
      preterm breech singletons with non-urgent CS, a statistical analysis was not
      possible due to small numbers. The VD twin group revealed lower values in birth
      weight, head circumference, arterial cord blood pH and BE, but no significant
      difference in venous cord blood pH and BE and transfer rate to NICU. CONCLUSIONS:
      Although general recommendations regarding a superior mode of delivery for
      improved fetal outcome of preterm breech infants cannot be given, these data do
      not support a policy of routine CS.

PMID- 24668253
TI  - MIROR: a method for cell-type specific microRNA occupancy rate prediction.
AB  - MicroRNA (miRNA) regulation is highly cell-type specific. It is sensitive to both
      the miRNA-mRNA relative abundance and the competitive endogenous RNA (ceRNA)
      effect. However, almost all existing miRNA target prediction methods neglected
      the influence of the cellular environment when analyzing miRNA regulation
      effects. In this study, we proposed a method, MIROR (miRNA Occupancy Rate
      predictor), to predict miRNA regulation intensity in a given cell type. The major
      considerations were the miRNA-mRNA relative abundance and the endogenous
      competition between different mRNA species. The output of MIROR is the predicted
      miRNA occupancy rates of each target site. The predicted results significantly
      correlated with Ago HITS-CLIP experiment that indicated miRNA binding
      intensities. When applied to the analysis of the breast invasive carcinoma
      dataset, MIROR identified a number of differentially regulated miRNA-mRNA pairs
      with significant miRNA occupancy rate changes between tumor and normal tissues.
      Many of the predictions were supported by previous research studies, including
      the ones without a significant change in the mRNA expression level. These results
      indicate that MIROR provides a novel strategy to study the miRNA differential
      regulation in different cell types. 

PMID- 24668254
TI  - Changes in sexual behavior of HIV-infected older adults enrolled in a clinical
      trial of standalone group psychotherapies targeting depression.
AB  - By 2015, one-half of all HIV-positive persons in the U.S. will be 50-plus years
      of age, and as many as 30 % of older adults living with HIV/AIDS continue to
      engage in unprotected sexual intercourse. Contemporary positive prevention models
      often include mental health treatment as a key component of HIV prevention
      interventions. This secondary data analysis characterized longitudinal patterns
      of sexual behavior in HIV-positive older adults enrolled in a randomized
      controlled trial of group mental health interventions and assessed the efficacy
      of psychosocial treatments that targeted depression to reduce sexual risk
      behavior. Participants were 295 HIV-positive adults >=50 years of age
      experiencing mild to severe depressive symptoms, randomized to one of three study
      conditions: a 12-session coping improvement group intervention, a 12-session
      interpersonal support group intervention, or individual therapy upon request.
      Approximately one-fifth of participants reported one or more occasions of
      unprotected anal or vaginal intercourse with HIV-negative sexual partners or
      persons of unknown HIV serostatus over the study period. Changes in sexual
      behavior did not vary by intervention condition, indicating that standalone
      treatments that target and reduce depression may be insufficient to reduce sexual
      risk behavior in depressed HIV-positive older adults.

PMID- 24668255
TI  - An efficient ruthenium-catalyzed dehydrogenative synthesis of 2,4,6-triaryl-1,3,5
      triazines from aryl methanols and amidines.
AB  - By using [RuCl2(p-Cymene)]2/Cs2CO3 as an efficient catalyst system, the readily
      available, inexpensive aryl methanols were firstly employed for dehydrogenative
      synthesis of aryl substituted 1,3,5-triazine derivatives. Due to the inherent
      stability of alcohols in contrast with aldehydes, our synthetic protocol is
      adaptable to a broad substrate scope, there is no need for stringent protection
      during the whole operation process, and it has the potential to prepare valuable
      products that are currently inaccessible or challenging to prepare using
      conventional methods. It is a significantly important complement to the
      conventional synthetic methodologies. 

PMID- 24668256
TI  - Endovascular treatment of unruptured wide-necked intracranial aneurysms:
      comparison of dual microcatheter technique and stent-assisted coil embolization.
AB  - BACKGROUND: Endovascular treatment of wide-necked aneurysms is challenging. Stent
      assisted coiling (SAC) is associated with increased complications and requires
      dual antiplatelet therapy. OBJECTIVE: To compare treatment of unruptured, wide
      necked aneurysms with a dual-microcatheter technique (DMT) versus SAC. METHODS:
      Between 2006 and 2011, 100 patients with unruptured wide-necked intracranial
      aneurysms were treated with DMT and 160 with SAC. Over time there was a
      significant decrease in the use of SAC and a corresponding increase in DMT. The
      investigators matched 60 patients treated with DMT blinded to outcome in a 1:2
      fashion based on maximal aneurysm dome diameter with 120 patients treated with
      SAC. Outcomes were determined with conditional (matched) multivariate analysis.
      RESULTS: There were no significant differences in patient or aneurysm
      characteristics between cohorts, including aneurysm diameter, neck width, or
      volume. Overall packing density and coil volume achieved was not significantly
      different between cohorts. There were higher rates of overall complications in
      those receiving SAC (19.2%) compared with DMT (5.0%; p=0.012), but no significant
      difference in major complications (8.3% vs 1.7%, respectively; p=0.103). At a
      mean follow-up of 27.0 +/- 18.9 months, rates of retreatment did not differ
      between DMT (15.1%) and SAC (17.7%). Delayed in-stent stenosis occurred in five
      patients and in-stent thrombosis in four patients treated with SAC. There was no
      difference in favorable functional outcome (modified Rankin score 0-2) between
      those treated with DMT (90.6%) compared with SAC (91.2%). CONCLUSIONS: DMT and
      SAC are effective endovascular approaches for unruptured, wide-necked aneurysms;
      however, DMT may result in less morbidity. Further long-term studies are
      necessary to determine the optimal indications for these treatment options.

PMID- 24668257
TI  - Mechanical properties and fibrin characteristics of endovascular coil-clot
      complexes: relevance to endovascular cerebral aneurysm repair paradigms.
AB  - BACKGROUND: Although coil embolization is known to prevent rebleeding from
      acutely ruptured cerebral aneurysms, the underlying biological and mechanical
      mechanisms have not been characterized. We sought to determine if microcoil
      dependent interactions with thrombus induce structural and mechanical changes in
      the adjacent fibrin network. Such changes could play an important role in the
      prevention of aneurysm rebleeding. METHODS: The stiffness of in vitro human blood
      clots and coil-clot complexes implanted into aneurysm phantoms were measured
      immediately after formation and after retraction for 3 days using unconfined
      uniaxial compression assays. Scanning electron microscopy of the coil-clot
      complexes showed the effect of coiling on clot structure. RESULTS: The coil
      packing densities achieved were in the range of clinical practice. Bare platinum
      coils increased clot stiffness relative to clot alone (Young's modulus 6.9 kPa
      and 0.83 kPa, respectively) but did not affect fibrin structure. Hydrogel-coated
      coils prevented formation of a clot and had no significant effect on clot
      stiffness (Young's modulus 2 kPa) relative to clot alone. Clot age decreased
      fiber density by 0.2 fibers/um(2) but not the stiffness of the bare platinum coil
      clot complex. CONCLUSIONS: The stiffness of coil-clot complexes is related to the
      summative stiffness of the fibrin network and associated microcoils. Hydrogel
      coated coils exhibit significantly less stiffness due to the mechanical
      properties of the hydrogel and the inhibition of fibrin network formation by the
      hydrogel. These findings have important implications for the design and
      engineering of aneurysm occlusion devices.

PMID- 24668258
TI  - Protein film photoelectrochemistry of the water oxidation enzyme photosystem II.
AB  - Photosynthesis is responsible for the sunlight-powered conversion of carbon
      dioxide and water into chemical energy in the form of carbohydrates and the
      release of O2 as a by-product. Although many proteins are involved in
      photosynthesis, the fascinating machinery of Photosystem II (PSII) is at the
      heart of this process. This tutorial review describes an emerging technique named
      protein film photoelectrochemistry (PF-PEC), which allows for the light-dependent
      activity of PSII adsorbed onto an electrode surface to be studied. The technique
      is straightforward to use, does not require highly specialised and/or expensive
      equipment, is highly selective for the active fractions of the adsorbed enzyme,
      and requires a small amount of enzyme sample. The use of PF-PEC to study PSII can
      yield insights into its activity, stability, quantum yields, redox behaviour, and
      interfacial electron transfer pathways. It can also be used in PSII inhibition
      studies and chemical screening, which may prove useful in the development of
      biosensors. PSII PF-PEC cells also serve as proof-of-principle solar water
      oxidation systems; here, a comparison is made against PSII-inspired synthetic
      photocatalysts and materials for artificial photosynthesis. 

PMID- 24668259
TI  - Fibroblast growth factor-23 and cardiovascular disease in the general population:
      the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) is a phosphate regulatory
      hormone that directly stimulates left ventricular hypertrophy in experimental
      models. The role of FGF-23 in cardiovascular disease development in the general
      population is unclear. We tested associations of FGF-23 with major subclinical
      and clinical cardiovascular disease outcomes in a large prospective cohort.
      METHODS AND RESULTS: We evaluated 6547 participants from the Multi-Ethnic Study
      of Atherosclerosis (MESA) who were initially free of cardiovascular disease. We
      measured serum FGF-23 using the Kainos immunoassay. The MESA measured left
      ventricular mass by MRI, coronary calcium by computed tomography, and carotid
      intima-media thickness by ultrasound. The MESA adjudicated incident heart
      failure, coronary heart disease, and stroke by medical record review. After
      adjustment, the highest FGF-23 quartile was associated with an estimated 2.4-g
      greater left ventricular mass (95% confidence interval, 0.4-4.5 greater) and a
      26% greater odds of higher coronary calcium scores (95% confidence interval, 9%
      46% greater) compared with the lowest quartile. During 7.5-year follow-up, each
      20-pg/mL higher FGF-23 concentration was associated with a 19% greater risk of
      heart failure (95% confidence interval, 3%-37% greater) and a 14% greater risk of
      coronary heart disease (95% confidence interval, 1%-28% greater). FGF-23 was not
      associated with carotid intima-media thickness or stroke. CONCLUSIONS: Higher
      serum FGF-23 concentrations are associated with subclinical cardiac disease and
      with new heart failure and coronary disease events, but not with carotid intima
      media thickness or stroke. FGF-23 may be a novel cardiovascular risk factor in
      the general population.

PMID- 24668260
TI  - A pro-inflammatory signalome is constitutively activated by C33Y mutant TNF
      receptor 1 in TNF receptor-associated periodic syndrome (TRAPS).
AB  - Mutations in TNFRSF1A encoding TNF receptor 1 (TNFR1) cause the autosomal
      dominant TNF receptor-associated periodic syndrome (TRAPS): a systemic
      autoinflammatory disorder. Misfolding, intracellular aggregation, and ligand
      independent signaling by mutant TNFR1 are central to disease pathophysiology. Our
      aim was to understand the extent of signaling pathway perturbation in TRAPS. A
      prototypic mutant TNFR1 (C33Y), and wild-type TNFR1 (WT), were expressed at near
      physiological levels in an SK-Hep-1 cell model. TNFR1-associated signaling
      pathway intermediates were examined in this model, and in PBMCs from C33Y TRAPS
      patients and healthy controls. In C33Y-TNFR1-expressing SK-Hep-1 cells and TRAPS
      patients' PBMCs, a subtle, constitutive upregulation of a wide spectrum of
      signaling intermediates and their phosphorylated forms was observed; these were
      associated with a proinflammatory/antiapoptotic phenotype. In TRAPS patients'
      PBMCs, this upregulation of proinflammatory signaling pathways was observed
      irrespective of concurrent treatment with glucocorticoids, anakinra or
      etanercept, and the absence of overt clinical symptoms at the time that the blood
      samples were taken. This study reveals the pleiotropic effect of a TRAPS
      associated mutant form of TNFR1 on inflammatory signaling pathways (a
      proinflammatory signalome), which is consistent with the variable and limited
      efficacy of cytokine-blocking therapies in TRAPS. It highlights new potential
      target pathways for therapeutic intervention. 

PMID- 24668261
TI  - Randomized trial of harp therapy during in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: This study evaluated whether harp therapy reduces levels of stress and
      improves clinical outcomes in patients undergoing embryo transfer. DESIGN: This
      prospective randomized trial enrolled 181 women undergoing embryo transfer, who
      were randomized to harp therapy during embryo transfer or standard treatment.
      Patients underwent standardized psychological testing and physiologic assessment
      of stress. SETTING: The study was conducted in a reproductive medicine practice.
      RESULTS: No statistically significant differences were found in the heart and
      respiratory rates, nor was there a significant difference in event-based anxiety
      at baseline. Harp therapy had a significantly larger decrease in state anxiety
      from pre- to post-embryo transfer. Clinical pregnancy was 53% versus 48% for the
      harp therapy and standard treatment groups, respectively. CONCLUSION: Harp
      therapy decreases state, or event-based, anxiety, significantly lowering state
      scores posttransfer and having a positive effect on acute levels of stress. There
      was an increased pregnancy rate, but larger sample sizes are needed to evaluate
      whether harp therapy has an effect on clinical outcomes.

PMID- 24668262
TI  - A variant of KCC2 from patients with febrile seizures impairs neuronal Cl-
      extrusion and dendritic spine formation.
AB  - Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation
      chloride cotransporter that is essential for hyperpolarizing GABAergic signaling
      and formation of cortical dendritic spines, has not been reported in human
      disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in
      an Australian family with febrile seizures. We show that KCC2-R952H reduces
      neuronal Cl(-) extrusion and has a compromised ability to induce dendritic spines
      in vivo and in vitro. Biochemical analyses indicate a reduced surface expression
      of KCC2-R952H which likely contributes to the functional deficits. Our data
      suggest that KCC2-R952H is a bona fide susceptibility variant for febrile
      seizures. 

PMID- 24668263
TI  - Somatic and axonal LIGHT signaling elicit degenerative and regenerative responses
      in motoneurons, respectively.
AB  - A receptor-ligand interaction can evoke a broad range of biological activities in
      different cell types depending on receptor identity and cell type-specific post
      receptor signaling intermediates. Here, we show that the TNF family member LIGHT,
      known to act as a death-triggering factor in motoneurons through LT-betaR, can
      also promote axon outgrowth and branching in motoneurons through the same
      receptor. LIGHT-induced axonal elongation and branching require ERK and caspase-9
      pathways. This distinct response involves a compartment-specific activation of
      LIGHT signals, with somatic activation-inducing death, while axonal stimulation
      promotes axon elongation and branching in motoneurons. Following peripheral nerve
      damage, LIGHT increases at the lesion site through expression by invading B
      lymphocytes, and genetic deletion of Light significantly delays functional
      recovery. We propose that a central and peripheral activation of the LIGHT
      pathway elicits different functional responses in motoneurons. 

PMID- 24668264
TI  - Structural determinants in GABARAP required for the selective binding and
      recruitment of ALFY to LC3B-positive structures.
AB  - Several autophagy proteins contain an LC3-interacting region (LIR) responsible
      for their interaction with Atg8 homolog proteins. Here, we show that ALFY binds
      selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of
      ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures
      and, thus, for the clearance of certain p62 structures by autophagy. In addition,
      the crystal structure of the GABARAP-ALFY-LIR peptide complex identifies three
      conserved residues in the GABARAPs that are responsible for binding to ALFY.
      Interestingly, introduction of these residues in LC3B is sufficient to enable its
      interaction with ALFY, indicating that residues outside the LIR-binding
      hydrophobic pockets confer specificity to the interactions with Atg8 homolog
      proteins. 

PMID- 24668266
TI  - Enhanced diffusion of tracer particles in dilute bacterial suspensions.
AB  - Swimming bacteria create long-range velocity fields that stir a large volume of
      fluid and move around passive particles dispersed in the fluid. Recent
      experiments and simulations have shown that long-time mean-squared displacement
      of passive particles in a bath of swimming bacteria exhibits diffusive behaviour
      with an effective diffusion coefficient significantly larger than its thermal
      counterpart. A comprehensive theoretical prediction of this effective diffusion
      coefficient and the understanding of the enhancement mechanism remain a
      challenge. Here, we adapt the kinetic theory by Lin et al., J. Fluid Mech., 2011,
      669, 167 developed for 'squirmers' to the bacterial case to quantitatively
      predict enhanced diffusivity of tracer particles in dilute two- and three
      dimensional suspensions of swimming bacteria. We demonstrate that the effective
      diffusion coefficient is a product of the bacterial number density, their
      swimming speed, a geometric factor characterising the velocity field created by a
      single bacterium, and a numerical factor. We show that the numerical factor is,
      in fact, a rather strong function of the system parameters, most notably the run
      length of the bacteria, and that these dependencies have to be taken into account
      to quantitatively predict the enhanced diffusivity. We perform molecular-dynamics
      type simulations to confirm the conclusions of the kinetic theory. Our results
      are in good agreement with the values of enhanced diffusivity measured in recent
      two- and three-dimensional experiments. 

PMID- 24668265
TI  - Tuning single-cell oil production in Ashbya gossypii by engineering the
      elongation and desaturation systems.
AB  - Microbial oils represent a sustainable alternative to vegetable oils and animal
      fats as feedstock for both the chemical and biofuel industries. The applications
      of microbial oils depend on their fatty acid composition, which is defined by the
      relative amount of each fatty acid, also considering the length and unsaturations
      of the acyl chain. These two properties are determined by elongases and
      desaturases. In the present study, we characterized the elongase and desaturase
      systems in the filamentous fungus Ashbya gossypii, which is able to accumulate
      high amounts of lipids. Additionally, both the elongation and desaturation
      systems were engineered in order to broaden the potential applications of A.
      gossypii oils. Finally, the properties of the strains engineered for biodiesel
      production were analyzed, with the observation that A. gossypii is a good
      candidate for the microbial production of renewable biofuels.

PMID- 24668267
TI  - [Mirror, mirror on the wall or writing on the wall?: publication performance of
      university anesthesiology departments].

PMID- 24668268
TI  - Learning from laboratory-induced falling: long-term motor retention among older
      adults.
AB  - Falls in older adults are a major health and societal problem. It is thus
      imperative to develop highly effective training paradigms to reduce the
      likelihood of falls. Perturbation training is one such emerging paradigm known to
      induce shorter term fall reduction in healthy young as well as older adults. Its
      longer term benefits are not fully understood, however. The purpose of this study
      was to determine whether and to what degree older adults could retain their fall
      resisting skills acquired from a single perturbation training session. Seventy
      three community-dwelling older adults (>=65 years) received identical single
      session perturbation training consisting of 24 slips. This was delivered through
      unannounced unlocking (and mixed with relocking) of low-friction movable sections
      of the walkway. A single retest was subsequently scheduled based on a three-stage
      sequential, pre-post-retest design. Outcome measurements, taken upon the first
      (novel) and the 24th (final) slips of the initial session and the retest slip,
      included fall-or-no-fall and stability (quantified by the shortest distance from
      relative motion state of the center-of-mass and the base-of-support to the limits
      of stability) at instants prior to (proactive) and after (reactive) the onset of
      the slip. The training boosted subjects' resilience against laboratory-induced
      falls demonstrated by a significant reduction from 42.5 % falls on the first slip
      to 0 % on the 24th slip. Rate of falls which occurred during the laboratory
      retest remained low in 6-month (0 %), 9-month (8.7 %), and 12-month retest (11.5
      %), with no significant difference between the three time intervals. Such
      reduction of laboratory-induced falls and its retention were attributable to the
      significant training-induced improvement in the proactive and reactive control of
      stability. This unique pre-post-retest design enabled us to provide scientific
      basis for the feasibility of a single session of perturbation training to
      "inoculate" older adults and to reduce their annual risk of falls in everyday
      living.

PMID- 24668269
TI  - Evaluation of a press-fit osteochondral poly(ester-urethane) scaffold in a rabbit
      defect model.
AB  - The purpose of this study was to evaluate the impact on osteochondral healing of
      press-fitted multiphasic osteochondral scaffolds consisting of poly(ester
      urethane) (PUR) and hydroxyapatite into a cylindric osteochondral defect in the
      distal non-weight bearing femoral trochlear ridge of the rabbit. Two scaffolds
      were investigated, one with and one without an intermediate microporous membrane
      between the cartilage and the bone compartment of the scaffold. A control group
      without a scaffold placed into the defect was included. After 12 weeks
      macroscopic and histomorphological analyses were performed. The scaffold was
      easily press-fitted and provided a stable matrix for tissue repair. The membrane
      did not demonstrate a detrimental effect on tissue healing compared with the
      scaffold without membrane. However, the control group had statistically superior
      healing as reflected by histological differences in the cartilage and subchondral
      bone compartment between control group and each scaffold group. A more detailed
      analysis revealed that the difference was localized in the bone compartment
      healing. The present study demonstrates that an elastomeric PUR scaffold can
      easily be press-fitted into an osteochondral defect and provides a stable matrix
      for tissue repair. However, the multi-phasic scaffold did not provide a clear
      advantage for tissue healing. Future investigations should refine especially the
      bone phase of the implant to increase its stiffness, biocompatibility and
      osteoconductive activity. A more precise fabrication technique would be necessary
      for the matching of tissue organisation. 

PMID- 24668270
TI  - Effect of structure, topography and chemistry on fibroblast adhesion and
      morphology.
AB  - Surface biofunctionalisation of many biodegradable polymers is one of the used
      strategies to improve the biological activity of such materials. In this work,
      the introduction of collagen type I over the surface of a biodegradable polymer
      (poly lactic acid) processed in the forms of films and fibers leads to an
      enhancing of the cellular adhesion of human dermal fibroblast when compared to
      unmodified polymer and biomolecule-physisorbed polymer surface. The change of
      topography of the material does not affect the cellular adhesion but results in a
      higher proliferation of the fibroblast cultured over the fibers. Moreover, the
      difference of topography governs the cellular morphology, i.e. cells adopt a more
      stretched conformation where cultured over the films while a more elongated with
      lower area morphology are obtained for the cells grown over the fibers. This
      study is relevant for designing and modifying different biodegradable polymers
      for their use as scaffolds for different applications in the field of Tissue
      Engineering and Regenerative Medicine. 

PMID- 24668271
TI  - Enhanced repair of a critical-sized segmental bone defect in rabbit femur by
      surface microstructured porous titanium.
AB  - Repair of load-bearing bone defects remains a challenge in the field of
      orthopaedic surgery. In the current study, a surface microstructured porous
      titanium (STPT) successively treated with H2O2/TaCl5 solution and simulated body
      fluid was used to repair the critical-sized segmental bone defects in rabbit
      femur, and non-treated porous titanium (NTPT) and porous biphasic calcium
      phosphate ceramics (PBCP) were used as control, respectively. A 15 mm long
      implant was positioned in the femoral defect and stabilized by a plate and screws
      fixation. After implantation into the body for 1, 3 and 6 months, X-ray
      observation confirmed that porous titanium groups (NTPT and STPT) provided better
      mechanical support than PBCP group at the early stage. However, there was no
      obvious difference in the formed bony callus between PBCP and STPT groups in the
      later stage, and they both showed better shape of bony callus than NTPT group.
      Micro-CT and histomorphometric analysis for the samples of 6-month implantation
      demonstrated that more new bone formed in the inner pores of PBCP and STPT groups
      than that in NTPT group. Moreover, the biomechanical tests revealed that STPT
      group could bear larger compressive load than NTPT and PBCP groups, almost
      reaching the level of the normal rabbit femur. STPT exhibited the enhanced
      repairing effect on the critical-sized segmental bone defect in rabbit femur,
      meaning that it could be an ideal material for the repair of large bone defect in
      load-bearing site. 

PMID- 24668272
TI  - A molecular and bioinformatic study on the ochratoxin A (OTA)-producing
      Aspergillus affinis (section Circumdati).
AB  - Aspergillus affinis (section Circumdati) is a novel ochratoxin A (OTA)-producing
      species found in submerged riparian decomposing leaves. However, very little is
      known about its role on the breakdown of plant debris and its ability to degrade
      carbohydrate polymers. Moreover, its OTA biosynthetic pathway has not yet been
      explored. In the present paper, we investigated the gene encoding the
      extracellular alpha-amylase (amyAa) of A. affinis within the evolution of the
      Aspergillus lineages in relation to the possible use of this enzyme in starch
      processing. The novel amyAa, despite being related to branches of the Aspergillus
      species of the sections Terrei and Flavi, formed a distinct phylogenetic branch,
      which may be of outstanding importance from a biotechnological point of view.
      Moreover, we identified the polyketide synthase gene (pks) putatively required
      for the first step of OTA biosynthesis in A. affinis. This otapks was examined in
      relation to a limited number of orthologous genes available from Aspergillus
      species of the sections Circumdati and Nigri. Our study highlights the importance
      of otapks as target genes in the treatment of ochratoxigenic Aspergillus species
      on a more comprehensive evolutionary basis. 

PMID- 24668273
TI  - Metallomics insights into the programmed cell death induced by metal-based
      anticancer compounds.
AB  - Since the discovery of cisplatin more than 40 years ago, enormous research
      efforts have been dedicated to developing metal-based anticancer agents and to
      elucidating the mechanisms involved in the action of these compounds. Abnormal
      metabolism and the evasion of apoptosis are important hallmarks of malignant
      transformation, and the induction of apoptotic cell death has been considered to
      be a main pathway by which cytotoxic metal complexes combat cancer. However, many
      cancers have cellular defects involving the apoptotic machinery, which results in
      an acquired resistance to apoptotic cell death and therefore reduced
      chemotherapeutic effectiveness. Over the past decade, it has been revealed that a
      growing number of cell death pathways induced by metal complexes are not
      dependent on apoptosis. Metal complexes specifically triggering these alternative
      cell death pathways have been identified and explored as novel cancer treatment
      options. In this review, we discuss recent examples of metallomics studies on the
      different types of cell death induced by metal-based anticancer drugs, especially
      on the three major forms of programmed cell death (PCD) in mammalian cells:
      apoptosis, autophagy and regulated necrosis, also called necroptosis. 

PMID- 24668275
TI  - Comment on: the EANM and SNMMI practice guideline for lymphoscintigraphy and
      sentinel node localization in breast cancer.

PMID- 24668276
TI  - Prognostic imaging of neuroblastoma.

PMID- 24668274
TI  - Individualized dosimetry-based activity reduction of 90Y-DOTATOC prevents severe
      and rapid kidney function deterioration from peptide receptor radionuclide
      therapy.
AB  - PURPOSE: Assessment of kidney function evolution after (90)Y-DOTATOC peptide
      receptor radionuclide therapy (PRRT) with capped activity administration based on
      a 37-Gy threshold of biological effective dose (BED) to the kidney. METHODS: In a
      prospective phase II study, patients with metastasized neuroendocrine tumours
      were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid
      coinfusion. Planar whole-body images were acquired at four time-points after
      injection and kidney volumes were measured using CT/MRI. BED to the kidneys was
      estimated using an extended BED formula and biexponential renal clearance. Based
      on published BED dose-toxicity relationships, we allowed a maximal kidney BED of
      37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced
      accordingly. Kidney function was assessed at baseline and at 18 months,
      predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed
      as annual glomerular filtration rate loss (aGFRL). RESULTS: Only 22 of 50
      patients reached the 18-months time-point, with most missing patients having died
      due to disease progression. In the 22 patients who reached 18 months, no rapid
      kidney function deterioration was observed over the 18 months, aGFRL >33% was not
      seen, and only three patients showed an increase of one toxicity grade and one
      patient an increase of two grades. No significant correlations between kidney
      volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss
      (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18
      months, one developed grade 4 kidney toxicity at 15 months after PRRT.
      CONCLUSION: Prospective dosimetry using a 37 Gy BED as the threshold for kidney
      toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk
      of rapid renal function deterioration and evolution to severe nephrotoxicity.

PMID- 24668277
TI  - Response to comment by Aprile et al.: the EANM and SNMMI practice guideline for
      lymphoscintigraphy and sentinel node localization in breast cancer.

PMID- 24668278
TI  - Authorship problems in scientific literature and in nuclear medicine: the point
      of view of the young researcher.

PMID- 24668279
TI  - Incapacitation recovery times from a conductive electrical weapon exposure.
AB  - PURPOSE: Law enforcement officers expect that a TASER((r)) CEW (Conducted
      Electrical Weapon) broad-spread probe exposure will temporarily incapacitate a
      subject who will then be able to immediately (~1 s delay) recover motor control
      in order to comply with commands. However, this recovery time has not been
      previously reported. METHODS: A total of 32 police academy students were exposed
      to a very broad-spread 5 s CEW stimulus as part of their training and told to
      depress a push-button as soon as they sensed the stimulus. A subgroup also
      depressed the push-button after being alerted by an audio stimulus. RESULTS: The
      response time after the audio trigger was 1.05 +/- 0.25 s; the median was 1.04 s
      (range 0.69-1.34 s). For the paired CEW triggered group the mean response time
      was 1.41 +/- 0.61 s with a median of 1.06 s (range 0.92-2.18 s), which was not
      statistically different. Only 2/32 subjects were able to depress the button
      during the CEW exposure and with delays of 3.09 and 4.70 s from the start. Of the
      remaining 30 subjects the mean response time to execute the task (once the CEW
      exposure ended) was 1.27 +/- 0.58 s with a median of 1.19 s (range 0.31-2.99 s)
      (NS vs. the audio trigger). CONCLUSIONS: With a very-broad electrode spread, a
      CEW exposure could prevent or delay some purposeful movements. Normal reaction
      times appear to return immediately (~1 s) after the CEW exposure ceases.

PMID- 24668280
TI  - Curcumin induces the apoptotic intrinsic pathway via upregulation of reactive
      oxygen species and JNKs in H9c2 cardiac myoblasts.
AB  - Curcumin derived from the rhizome of turmeric (Curcuma longa L.), is a well known
      coloring culinary agent, that has therapeutic properties against diverse
      pathologies such as cancer, atherosclerosis and heart failure. Given the salutary
      potential of curcumin, deciphering its mode of action particularly in cardiac
      cells, is of outstanding value. Accumulating evidence implicates curcumin in the
      regulation of multiple signaling pathways leading to cell survival or apoptosis.
      Therefore, the present study aimed at elucidating the molecular mechanisms
      triggered by curcumin in H9c2 cells. Curcumin was found to activate p38-mitogen
      activated protein kinase (p38-MAPK) as well as c-jun NH2 terminal kinases (JNKs),
      in a dose- and time-dependent manner. We also observed curcumin to impair cell
      survival by promoting apoptosis, evidenced by chromatin condensation, poly(ADP
      ribose) polymerase (PARP) and caspase-3 cleavage, as well as Bax translocation
      and cytochrome c release into the cytosol. Curcumin-induced apoptosis was
      ascribed to JNKs, since hindering their activity abolished PARP fragmentation.
      Furthermore, we identified curcumin to exert a pro-oxidative activity, with 2',7'
      dichlorofluorescin diacetate (DCFH-DA) staining revealing up-regulation of
      reactive oxygen species (ROS) levels and anti-oxidants found to abrogate PARP
      cleavage. In conclusion, curcumin was found to stimulate the apoptotic cell death
      of H9c2 cells by upregulating ROS generation and triggering activation of JNKs.
      With reports underscoring the capacity of curcumin to perturb the cellular redox
      balance ensuring survival or enhancing apoptosis, determination of its mode of
      action appears to be critical. Future studies should assess the appropriate
      administration conditions of curcumin, so as to optimize its therapeutic
      potential against cardiovascular pathologies.

PMID- 24668281
TI  - Copper-mediated S-N formation via an oxygen-activated radical process: a new
      synthesis method for sulfonamides.
AB  - Copper-mediated direct S-N formation using readily available starting materials
      via an oxygen-activated radical process has been developed. This method provides
      a novel and direct approach for synthesis of sulfonamides under air conditions. 

PMID- 24668282
TI  - Tantalum-based semiconductors for solar water splitting.
AB  - Solar energy utilization is one of the most promising solutions for the energy
      crises. Among all the possible means to make use of solar energy, solar water
      splitting is remarkable since it can accomplish the conversion of solar energy
      into chemical energy. The produced hydrogen is clean and sustainable which could
      be used in various areas. For the past decades, numerous efforts have been put
      into this research area with many important achievements. Improving the overall
      efficiency and stability of semiconductor photocatalysts are the research focuses
      for the solar water splitting. Tantalum-based semiconductors, including tantalum
      oxide, tantalate and tantalum (oxy)nitride, are among the most important
      photocatalysts. Tantalum oxide has the band gap energy that is suitable for the
      overall solar water splitting. The more negative conduction band minimum of
      tantalum oxide provides photogenerated electrons with higher potential for the
      hydrogen generation reaction. Tantalates, with tunable compositions, show high
      activities owning to their layered perovskite structure. (Oxy)nitrides,
      especially TaON and Ta3N5, have small band gaps to respond to visible-light,
      whereas they can still realize overall solar water splitting with the proper
      positions of conduction band minimum and valence band maximum. This review
      describes recent progress regarding the improvement of photocatalytic activities
      of tantalum-based semiconductors. Basic concepts and principles of solar water
      splitting will be discussed in the introduction section, followed by the three
      main categories regarding to the different types of tantalum-based
      semiconductors. In each category, synthetic methodologies, influencing factors on
      the photocatalytic activities, strategies to enhance the efficiencies of
      photocatalysts and morphology control of tantalum-based materials will be
      discussed in detail. Future directions to further explore the research area of
      tantalum-based semiconductors for solar water splitting are also discussed. 

PMID- 24668284
TI  - An analytical model for calculating internal dose conversion coefficients for non
      human biota.
AB  - To assess the radiation burden of non-human living organisms, dose coefficients
      are available in the literature, precalculated by assuming an ellipsoidal shape
      of each organism. A previously developed analytical method was applied for the
      determination of absorbed fractions inside ellipsoidal volumes from alpha, beta,
      and gamma radiations to the calculation of dose conversion coefficients (DCCs)
      for 15 reference organisms, animals and plants, either terrestrial, amphibian, or
      aquatic, and six radionuclides ((14)C, (90)Sr, (60)Co, (137)Cs, (238)U, and
      (241)Am). The results were compared with the reference values reported in
      Publication 108 of the International Commission on Radiological Protection, in
      which a different calculation approach for DCCs was employed. The results
      demonstrate that the present analytical method, originally intended for
      applications in internal dosimetry of nuclear medicine therapy, gives consistent
      results for all the beta-, beta-gamma-, and alpha-emitting radionuclides tested
      in a wide range of organism masses, between 8 mg and 1.3 kg. The applicability of
      the method proposed can take advantage from its ease of implementation in an
      ordinary electronic spreadsheet, allowing to calculate, for virtually all
      possible radionuclide emission spectra, the DCCs for ellipsoidal models of non
      human living organisms in the environment.

PMID- 24668285
TI  - The effect of dye coverage on the performance of dye-sensitized solar cells with
      a cobalt-based electrolyte.
AB  - The effect of dye coverage of the mesoporous TiO2 electrode on the performance of
      dye-sensitized solar cells based on the cobalt tris(bipyridine) electrolyte and
      the D35 dye was studied in detail. The dye coverage was controlled by using a dye
      bath with different dye concentrations and containing an inert salt, LiClO4,
      which was found to promote equilibrium conditions in the dye adsorption process.
      The amount of adsorbed D35 dye on mesoporous TiO2 was reasonably fit using the
      Langmuir adsorption isotherm, with a binding constant of 55 000 M(-1). Upon
      increasing the dye coverage on the TiO2 electrode, the electron lifetime in the
      dye-sensitized solar cell increased remarkably, demonstrating the blocking
      behavior of the D35 dye at the TiO2-electrolyte interface. Consequently, the
      solar cell efficiency increased dramatically with the D35 dye coverage. 

PMID- 24668283
TI  - Returning to tricyclic antidepressants for depression during childbearing:
      clinical and dosing challenges.
AB  - Managing depression and anxiety during pregnancy and the postpartum period is
      challenging. Both pharmacological treatment and the lack thereof can pose threats
      to a fetus. SSRIs are the drugs of choice for use during pregnancy, but there is
      considerable evidence for the safety and efficacy of older antidepressants during
      pregnancy as well. This study highlights a single case of the use of the
      tricyclic nortriptyline during pregnancy and postpartum. The subject involved had
      an unexpectedly high ratio of serum level to drug dose during the postpartum
      period. We monitored the subject for a significantly greater portion of the
      postpartum period than has been done in previous studies, and explored medical
      and lifestyle changes that could account for the level-to-dose ratios we
      observed. Differences in smoking patterns, coupled with the patient's status as a
      genetic poor metabolizer, were the most likely explanations. 

PMID- 24668287
TI  - Double exchange in a mixed-valent octanuclear iron cluster, [Fe8(MU4-O)4(MU-4-Cl
      pz)12Cl4](-).
AB  - A combination of SQUID and pulsed high-field magnetometry is used to probe the
      nature of mixed valency in an Fe(II)Fe7(III) cluster. DFT-computed spin
      Hamiltonian parameters suggest that antiferromagnetic coupling dominates, and
      that electron transfer both between the four irons of the cubane core (t1) and
      between a cubane and three neighboring irons (t2) is significant. Simulations
      using the computed parameters are able to reproduce the key features of the
      measured effective magnetic moment, MUeff(T), over the 2 < T < 300 K temperature
      range. In contrast, the field dependence of the molar magnetization, Mmol,
      measured at 0.4 K is inconsistent with substantial electron transfer: only values
      of t2~ 0 place the separation between ground and first excited states in the
      region indicated by experiment. The apparent quenching of the cubane-outer
      electron transfer at very low temperatures indicates that vibronic coupling
      generates one or more shallow minima on the adiabatic potential energy surfaces
      that serve to trap the itinerant electron in the cubane core. 

PMID- 24668286
TI  - Percutaneous closure of postinfarction ventricular septal defect: in-hospital
      outcomes and long-term follow-up of UK experience.
AB  - BACKGROUND: Postinfarction ventricular septal defect carries a grim prognosis.
      Surgical repair offers reasonable outcomes in patients who survive a healing
      phase. Percutaneous device implantation represents a potentially attractive early
      alternative. METHODS AND RESULTS: Postinfarction ventricular septal defect
      closure was attempted in 53 patients from 11 centers (1997-2012; aged 72+/-11
      years; 42% female). Nineteen percent had previous surgical closure. Myocardial
      infarction was anterior (66%) or inferior (34%). Time from myocardial infarction
      to closure procedure was 13 (first and third quartiles, 5-54) days. Devices were
      successfully implanted in 89% of patients. Major immediate complications included
      procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt
      reduction was graded as complete (23%), partial (62%), or none (15%). Median
      length of stay after the procedure was 5.0 (2.0-9.0) days. Fifty-eight percent
      survived to discharge and were followed up for 395 (63-1522) days, during which
      time 4 additional patients died (7.5%). Factors associated with death after
      postinfarction ventricular septal defect closure included the following: age
      (hazard ratio [HR]=1.04; P=0.039), female sex (HR=2.33; P=0.043), New York Heart
      Association class IV (HR=4.42; P=0.002), cardiogenic shock (HR=3.75; P=0.003),
      creatinine (HR=1.007; P=0.003), defect size (HR=1.09; P=0.026), inotropes
      (HR=4.18; P=0.005), and absence of revascularization therapy for presenting
      myocardial infarction (HR=3.28; P=0.009). Prior surgical closure (HR=0.12;
      P=0.040) and immediate shunt reduction (HR=0.49; P=0.037) were associated with
      survival. CONCLUSIONS: Percutaneous closure of postinfarction ventricular septal
      defect is a reasonably effective treatment for these extremely high-risk
      patients. Mortality remains high, but patients who survive to discharge do well
      in the longer term.

PMID- 24668288
TI  - Nanoconfinement effects on the fragility of glass formation of a model
      freestanding polymer film.
AB  - Evidence suggests that the fragility (m) of glass formation both underpins and is
      sensitive to nanoconfinement effects on the glass transition. Here we present
      data indicating that nanoconfinement-induced changes in m of freestanding films
      emerge from a dominance of finite-size-driven fragility suppression over
      interfacial fragility enhancement. 

PMID- 24668289
TI  - Absolute and comparative cancer risk perceptions among smokers in two cities in
      China.
AB  - INTRODUCTION: Knowledge about health effects of smoking motivates quit attempts
      and sustained abstinence among smokers and also predicts greater acceptance of
      tobacco control efforts such as cigarette taxes and public smoking bans. We
      examined whether smokers in China, the world's largest consumer of cigarettes,
      recognized their heightened personal risk of cancer relative to nonsmokers.
      METHODS: A sample of Chinese people (N = 2,517; 555 current smokers) from 2
      cities (Beijing and Hefei) estimated their personal risk of developing cancer,
      both in absolute terms (overall likelihood) and in comparative terms (relative to
      similarly aged people). RESULTS: Controlling for demographics, smokers judged
      themselves to be at significantly lower risk of cancer than did nonsmokers on the
      comparative measure. No significant difference emerged between smokers and
      nonsmokers in absolute estimates. CONCLUSIONS: Smokers in China did not recognize
      their heightened personal risk of cancer, possibly reflecting ineffective warning
      labels on cigarette packs, a positive affective climate associated with smoking
      in China, and beliefs that downplay personal vulnerability among smokers (e.g., I
      don't smoke enough to increase my cancer risk; I smoke high-quality cigarettes
      that won't cause cancer).

PMID- 24668290
TI  - Does physical activity have an impact on sickness absence? A review.
AB  - Increasing levels of physical activity are proven to have a positive impact on
      physical health and mental well-being. Physical activity is also known to
      influence work-related outcomes such as reducing sickness absence. Sickness
      absence is a major public health problem with wide economic impact on society and
      there may be much to gain from physical activity interventions aimed at
      preventing long-term sickness absence. Examining the relationship between
      physical activity and sickness absence is therefore important as it may provide
      benefits to organisations globally. This article provides a review of the
      evidence on the relationship between physical activity and sickness absence among
      employees. A search of databases (Web of Science, ScienceDirect, MEDLINE and
      Google Scholar) and references of published studies (from inception to 14
      November 2012) were conducted to identify intervention studies and observational
      studies involving employees. A total of 37 studies published between 1981 and
      2012 met the inclusion criteria. Evidence from the review suggests that physical
      activity is effective in reducing sickness absence. However, the studies
      highlighted a number of methodological concerns, including lack of description of
      the physical activity programme in intervention studies and use of self-report
      physical activity in observational studies. We conclude that, overall, the
      available evidence provides limited support that physical activity is effective
      in reducing sickness absence, due to the low quality of many of these studies.
      Future research should provide more detailed descriptions of the physical
      activity programme and use more reliable objective measures of physical activity
      such as accelerometers and fitness tests. 

PMID- 24668292
TI  - Sport-specific balance develops specific postural skills.

PMID- 24668293
TI  - Exercise in heart failure patients: why and how should nurses care?

PMID- 24668291
TI  - Pain during and within hours after exercise in healthy adults.
AB  - Literature on the pain relieving effects of exercise has been reviewed several
      times. It is equally important to review the literature on the pain-inducing
      effects of exercise. Indeed, exercise professionals, health care providers, and
      exercisers must grapple with the fact that exercise can both induce and reduce
      pain. The objective of this review was to synthesize our current understanding of
      exercise-induced pain and inspire advanced research. We searched the PubMed
      database for publications since 2000 about healthy human participants. Disease
      specific reviews of the effects of exercise are available elsewhere. The results
      of our literature review verified that many different modes, intensities, and
      durations of exercise can induce pain in healthy people. Another important point
      is that pain can occur within a few hours after eccentric contractions, which
      should be considered relative to the construct of delayed-onset muscle soreness.
      In addition, the studies supported that exercise can be painful in diverse muscle
      groups. Yet another point illuminated by the literature is that different pain
      measures do not always change in similar directions and magnitudes after
      exercise. Therefore, our review confirms that a wide variety of exercises can be
      painful--even for healthy people. We wonder how many exercise professionals and
      health care providers regularly and appropriately measure exercise-related pain
      or consider such pain in their exercise recommendations. We also question if
      exercise-related pain affects exercise behavior in healthy people as it has been
      shown to do in people with chronic illnesses. Additional research is needed to
      improve both exercise recommendations and exercise behavior.

PMID- 24668294
TI  - Kinome profiling of osteoblasts on hydroxyapatite opens new avenues on
      biomaterial cell signaling.
AB  - In degenerative diseases or lesions, bone tissue replacement and regeneration are
      important clinical goals. The most used bone substitutes today are hydroxyapatite
      (HA) scaffolds. These scaffolds, developed over the last few decades, present
      high porosity and good osteointegration, but haven't completely solved issues
      related to bone defects. Moreover, the exact intracellular mechanisms involved in
      the response to HA have yet to be addressed. This prompted us to investigate the
      protein networks responsible for signal transduction during early osteoblast
      adhesion on synthetic HA scaffolds. By performing a global kinase activity assay,
      we showed that there is a specific molecular machinery responding to HA contact,
      immediately triggering pathways leading to cytoskeleton rearrangement due to
      activation of Adducin 1 (ADD1), protein kinase A (PKA), protein kinase C (PKC),
      and vascular endothelial growth factor (VEGF). Moreover, we found a significantly
      increased phosphorylation of the activating site Ser-421 in histone deacetylase 1
      (HDAC1), a substrate of Cyclin-Dependent Kinase 5 (CDK5). These phosphorylation
      events are hallmarks of osteoblast differentiation, pointing to HA surfaces
      ability to promote differentiation. We also found that AKT was kept active,
      suggesting the maintenance of survival pathways. Interestingly, though, the
      substrate sequence of CDK5 also presented higher phosphorylation levels when
      compared to control conditions. To our knowledge, this kinase has never before
      been related to osteoblast biology, opening a new avenue of investigation for
      novel pathways involved in this matter. These results suggest that HA triggers a
      specific intracellular signal transduction cascade during early osteoblast
      adhesion, activating proteins involved with cytoskeleton rearrangement, and
      induction of osteoblast differentiation.

PMID- 24668296
TI  - Global overview of primary immunodeficiencies: a report from Jeffrey Modell
      Centers worldwide focused on diagnosis, treatment, and discovery.
AB  - Primary immunodeficiencies (PI) are defects of the immune system that cause
      severe infections if not diagnosed and treated appropriately. Many patients with
      PI are undiagnosed, under-diagnosed, or misdiagnosed. Over the last decade, the
      Jeffrey Modell Foundation has implemented a Physician Education and Public
      Awareness Campaign (PEPAC) to raise awareness, assure early diagnosis,
      appropriate treatment, and management, with the overall goal to reduce
      morbidities and mortalities related to PI. In order to evaluate the PEPAC
      program, data are requested annually from physician experts within the Jeffrey
      Modell Centers Network (JMCN). The JMCN, consisting of 556 expert physicians, at
      234 academic institutions, in 196 cities, and 78 countries spanning six
      continents, provides the infrastructure for referral, diagnosis, and appropriate
      treatment for patients with PI. In addition, the JMCN has made a significant
      contribution to the field of immunology with the discovery of new genes at the
      centers. These advancements have led to an overall better understanding of the
      immune system and will continue to improve quality of life of those with PI. 

PMID- 24668297
TI  - Acute disseminated encephalomyelitis progressing to multiple sclerosis: are
      infectious triggers involved?
AB  - Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are
      demyelinating disorders affecting the central nervous system. An autoimmune
      aetiology has been proposed for both. ADEM principally affects adolescents
      following acute infection by a variety of pathogens and has also been reported to
      occur following vaccination. ADEM typically resolves following medical treatment,
      whereas MS follows a more relapsing and remitting course. The pathogenesis of MS
      remains unclear, but it is thought that a combination of infectious and non
      infectious environmental factors and host genetics act synergistically to cause
      disease. A variety of viruses, including Epstein Barr virus, cytomegalovirus,
      herpes simplex virus and varicella zoster virus, have been implicated as possible
      infectious triggers. The similar clinical and pathological presentation of ADEM
      and MS presents a diagnostic challenge for distinguishing ADEM from a first
      episode of MS. Some cases of ADEM progress to MS for reasons that are not
      currently clear. This review examines the evidence for infectious agents as
      triggers for ADEM progressing to MS and suggests potential methods that may
      facilitate identification of infectious agents that may be responsible for the
      pathogenesis of ADEM to MS. 

PMID- 24668298
TI  - Dimeric pyrrolidinoindoline-type alkaloids with melanogenesis inhibitory activity
      in flower buds of Chimonanthus praecox.
AB  - A methanol extract of the flower buds of Chimonanthus praecox (L.) Link
      (Calycanthaceae) demonstrated inhibitory effects on melanogenesis in theophylline
      stimulated murine B16 melanoma 4A5 cells. From the extract, five dimeric
      pyrrolidinoindoline alkaloids and four sesquiterpenes were isolated, together
      with 16 known compounds. Among them, (-)-chimonanthine (1, IC50 = 0.93 MUM), (-)
      folicanthine (2, 1.4 MUM), and (-)-calycanthidine (3, 1.8 MUM) showed potent
      inhibitory effects without notable cytotoxicity at the effective concentrations.
      The most potent alkaloid (1) inhibited both tyrosinase and tyrosine-related
      protein-1 mRNA expressions, to which the melanogenesis inhibitory activity would
      be ascribable. 

PMID- 24668299
TI  - Screening of neonatal UK dried blood spots using a duplex TREC screening assay.
AB  - PURPOSE: Severe Combined Immunodeficiency (SCID) is considered to be a paediatric
      emergency and unless identified promptly can be life-threatening. Frequently,
      infants are not diagnosed with SCID until they have become seriously ill with
      infection leading to treatment complications and a poorer prognosis. We aimed to
      test a newly available commercial duplex assay to measure T cell receptor
      excision circles (TRECs) to establish if this would be suitable for newborn
      screening for SCID in the UK. METHODS: Over 5000 anonymous retrospective dried
      blood spots (DBS) were used alongside 18 confirmed SCID positive DBS with a newly
      available duplex assay to measure TRECs levels and control gene levels. We also
      included testing of premature babies and babies from neonatal intensive care
      units (NICU) as these have been shown to have high false positive rates in other
      TREC screening assays. RESULTS: All 18 SCID DBS samples were successfully
      identified as SCID positives in the study. The number of presumptive positives
      detected was dependent on the TREC cut-off threshold settings. When analysed with
      five different TRECs cut-off values (20, 25, 30, 35 and 40 TREC copies/MUl blood)
      the presumptive positive rate ranged from 0.04 to 1.00 % of samples tested.
      Premature infants and neonates from NICU did not show high presumed false
      positive rates in this assay. CONCLUSIONS: The study demonstrated that this
      duplex assay kit will identify all newborns with SCID as presumptive positives.
      The data also shows that with suitable TREC cut-off settings the number of
      presumptive positives from non-SCID newborns will be manageable in the context of
      a national screening service.

PMID- 24668301
TI  - Shape selection in chiral ribbons: from seed pods to supramolecular assemblies.
AB  - We provide a geometric-mechanical model for calculating equilibrium
      configurations of chemical systems that self-assemble into chiral ribbon
      structures. The model is based on incompatible elasticity and uses dimensionless
      parameters to determine the equilibrium configurations. As such, it provides
      universal curves for the shape and energy of self-assembled ribbons. We provide
      quantitative predictions for the twisted-to-helical transition, which was
      observed experimentally in many systems, and demonstrate it with synthetic
      ribbons made of responsive gels. In addition, we predict the bi-stability of wide
      ribbons and also show how geometrical frustration can cause arrest of ribbon
      widening. Finally, we show that the model's predictions provide explanations for
      experimental observations in different chemical systems. 

PMID- 24668300
TI  - Altered miRNAs expression profiles and modulation of immune response genes and
      proteins during neonatal sepsis.
AB  - PURPOSE: The dysregulated expression of miRNAs in the immune system may be
      critical for immune responses to pathogens and evolve into the inflammation seen
      in sepsis. The aim of this study is to explore the important role of miRNAs in
      the regulation of the immune response during neonatal sepsis. METHODS: Using a
      microarray we performed the miRNA expression profiling of peripheral blood
      leukocytes from neonates with sepsis and uninfected neonates. Based on the
      predicted target genes of these miRNAs we selected 26 immune-related miRNAs out
      of the differentially expressed miRNAs for further testing by quantitative PCR.
      We simultaneously detected the immune response genes by PCR array and plasma
      cytokine levels using a protein chip to investigate the effect of the altered
      miRNAs on the immune response in neonatal sepsis. RESULTS: There were 10 immune
      regulatory miRNAs whose expression was significantly changed more than two fold
      in the neonates with sepsis compared with the uninfected neonates. The expression
      levels of 11 immune response genes and the plasma levels of 15 cytokines or
      receptors were significantly up- or down-regulated in the neonates with sepsis
      compared to the uninfected neonates. This comprehensive analysis suggests that
      the altered miRNAs modulate the immune response during neonatal sepsis in a way
      that represses the inflammatory response. CONCLUSIONS: Our investigation
      demonstrated some miRNAs with altered expression levels and their probable
      association with the regulation of immune response during neonatal sepsis. The
      characteristics of the neonatal inflammatory response could be attributed to
      immature immune function of neonates.

PMID- 24668302
TI  - Zeolitic imidazolate framework composite membranes and thin films: synthesis and
      applications.
AB  - Zeolitic imidazolate frameworks (ZIFs), a subclass of metal organic frameworks,
      are built of tetrahedral metal ions bridged by imidazolates. They have permanent
      porosity and relatively high thermal and chemical stability, which make them
      attractive candidates for many industrial applications. In recent years,
      significant progress has been made in developing ZIFs into membranes and thin
      films for gas separation, liquid separation (pervaporation) and functional
      devices. Various techniques, such as direct synthesis, secondary synthesis,
      reactive seeding and functional chemicals as linkers, and contra-diffusion
      synthesis, have been reported for the fabrication of ZIF membranes and films. As
      ZIFs have good compatibility with polymers, they have been incorporated into
      polymers with high loadings to form mixed matrix membranes. The resulting
      symmetric dense or asymmetric composite membranes exhibit good performance in gas
      separation and liquid separation via pervaporation. The recent developments of
      ZIF membranes/films, ZIF-polymer mixed matrix membranes and their applications
      are reviewed in this article. 

PMID- 24668303
TI  - Bulky toroidal and vesicular self-assembled nanostructures from fullerene end
      capped rod-like polymers.
AB  - In this work, we present novel fullerene (C60) end-capped rod-like polypeptide
      polymers, obtained by one-pot thiol-ene chemistry. These systems are able to self
      assemble in water creating precise bulky microstructures of toroidal or vesicular
      shapes. Independent molecular dynamics simulations supported the observed
      experimental results. 

PMID- 24668304
TI  - Motivational interviewing targeting risky sex in HIV-positive young Thai men who
      have sex with men.
AB  - Motivational interviewing (MI) has been shown to reduce sexual risks among HIV
      positive men who have sex with men (HMSM) in the US. We conducted a randomized
      trial of Healthy Choices, a 4-session MI intervention, targeting sexual risks
      among 110 HIV-positive youth ages 16-25 years in Thailand. Risk assessments were
      conducted at baseline, 1 month, and 6 months post-intervention. This report
      presents the analysis of 74 HMSM in the study. There were 37 HMSM in the
      Intervention group and 37 in the control group. The proportions of participants
      having anal sex and having sex with either HIV-uninfected or unknown partners in
      past 30 days were significantly lower in Intervention group than in Control group
      at 6 months post-intervention (38 vs. 65 %, p = .04; and 27 vs. 62 %, p < .01,
      respectively). There were no significant differences in general mental health
      scores and HIV stigma scores between the two groups at any study visit. Thirty
      five (95 %) HMSM in the Intervention group vs. 31 (84 %) in control group
      attended >= 3 sessions. Loss to follow-up was 8 and 30 %, respectively (p = .04).
      Healthy Choices for young Thai HMSM was associated with sexual risk reduction.
      Improvements in mental health were noted in Intervention group. Healthy Choices
      is a promising behavioral intervention and should be further developed to serve
      the needs of young HMSM in resource-limited countries. 

PMID- 24668306
TI  - Tailoring the magnetic properties and magnetorheological behavior of spinel
      nanocrystalline cobalt ferrite by varying annealing temperature.
AB  - Magnetic nanoparticles of spinel nanocrystalline cobalt ferrite were synthesized
      via the sol-gel method and subsequent annealing. The influence of the annealing
      temperature on the structure, magnetic properties, and magnetorheological effect
      was investigated. The finite crystallite size of the particles, determined by X
      ray diffraction and the particle size observed via transmission electron
      microscopy, increased with the annealing temperature. The magnetic properties
      observed via a vibrating sample magnetometer showed that an increase in the
      annealing temperature leads to the increase in the magnetization saturation and,
      in contrast, a decrease in the coercivity. The effect of annealing on the
      magnetic properties of ferrite particles has been explained by the
      recrystallization process at high temperatures. This resulted in grain size
      growth and a decrease in an imposed stress relating to defects in the crystal
      lattice structure of the nanoparticles. The magnetorheological characteristics of
      suspensions of ferrite particles in silicone oil were measured using a rotational
      rheometer equipped with a magnetic field generator in both steady shear and small
      strain oscillatory regimes. The magnetorheological performance expressed as a
      relative increase in the magnetoviscosity appeared to be significantly higher for
      suspensions of particles annealed at 1000  degrees C. 

PMID- 24668305
TI  - SGI-110 and entinostat therapy reduces lung tumor burden and reprograms the
      epigenome.
AB  - The DNA methyltransferase (DNMT) inhibitor vidaza (5-Azacytidine) in combination
      with the histone deacetylase inhibitor entinostat has shown promise in treating
      lung cancer and this has been replicated in our orthotopic lung cancer model.
      However, the effectiveness of DNMT inhibitors against solid tumors is likely
      impacted by their limited stability and rapid inactivation by cytidine deaminase
      (CDA) in the liver. These studies were initiated to test the efficacy of SGI-110,
      a dinucleotide containing decitabine that is resistant to deamination by CDA, as
      a single agent and in combination with entinostat. Evaluation of in vivo plasma
      concentrations and pharmacokinetic properties of SGI-110 showed rapid conversion
      to decitabine and a plasma half-life of 4 hr. SGI-110 alone or in combination
      with entinostat reduced tumor burden of a K-ras/p53 mutant lung adenocarcinoma
      cell line (Calu6) engrafted orthotopically in nude rats by 35% and 56%,
      respectively. SGI-110 caused widespread demethylation of more than 300 gene
      promoters and microarray analysis revealed expression changes for 212 and 592
      genes with SGI-110 alone or in combination with entinostat. Epigenetic therapy
      also induced demethylation and expression of cancer testis antigen genes that
      could sensitize tumor cells to subsequent immunotherapy. In the orthotopically
      growing tumors, highly significant gene expression changes were seen in key
      cancer regulatory pathways including induction of p21 and the apoptotic gene BIK.
      Moreover, SGI-110 in combination with entinostat caused widespread epigenetic
      reprogramming of EZH2-target genes. These preclinical in vivo findings
      demonstrate the clinical potential of SGI-110 for reducing lung tumor burden
      through reprogramming the epigenome. 

PMID- 24668307
TI  - Evaluation of an automatic method for forensic age estimation by magnetic
      resonance imaging of the distal tibial epiphysis--a preliminary study focusing on
      the 18-year threshold.
AB  - The contribution of magnetic resonance imaging to forensic age estimation of
      living individuals is a subject of ongoing research. Several studies have focused
      on the wrist, clavicle, knee, and foot, and shown interesting results regarding
      the 18-year threshold. Authors have developed various staging systems for
      epiphyseal growth plate maturation. However, the procedure is observer-dependent
      and requires experience and a certain time-learning process. To reduce these
      pitfalls, we have developed an automatic method based on the analysis of
      variations of gray levels within the epiphyseal-metaphyseal junction. This method
      was tested on 160 MRI scans of the distal tibial epiphysis in a sample of
      individuals aged from 8 to 25 years old, after intensity non-uniformity
      correction of all images. Results showed that in our sample, 97.4 % of males and
      93.9 % of females aged 18 years or more would be correctly classified using this
      method. To our knowledge, automatic methods for MRI analysis have not been used
      in the field of age estimation yet. Further studies should be performed to assess
      the validity of this procedure.

PMID- 24668308
TI  - Safety and outcome of combined liver and pancreatic resections.
AB  - BACKGROUND: In Western countries, combined liver and pancreatic resections (CLPR)
      are performed rarely because of the perceived high morbidity and mortality rates.
      This study evaluated the safety and outcomes of CLPR at a tertiary European
      centre for hepatopancreatobiliary surgery. METHODS: A review of two prospectively
      maintained databases for pancreatic and liver resections was undertaken to
      identify patients undergoing CLPR between January 1994 and January 2012.
      Clinicopathological and surgical outcomes were analysed. Univariable and
      multivariable analyses for postoperative morbidity were performed. RESULTS: Fifty
      consecutive patients with a median age of 58 (range 20-81) years underwent CLPR.
      Indications for surgery were neuroendocrine carcinoma (16 patients), biliary
      cancer (15), colonic cancer (5), duodenal cancer (1) and others (13). The type of
      pancreatic resection included pancreaticoduodenectomy (30), distal pancreatectomy
      (17), spleen-preserving distal pancreatectomy (2) and total pancreatectomy (1).
      Twenty-three patients had associated major hepatectomies, 27 underwent minor
      liver resections and 11 had associated vascular resections. Mortality and
      morbidity rates were 4 and 46 per cent respectively. Univariable and
      multivariable analysis showed no differences in postoperative morbidity in
      relation to extent of liver resection or type of pancreatic resection. Use of
      preoperative chemotherapy was the only independent risk factor associated with
      postoperative morbidity (P = 0.021). CONCLUSION: CLPR can be performed with
      fairly low morbidity and mortality rates. Postoperative outcomes were not
      affected by the extent of liver resection or the type of pancreatic resection.
      Patients receiving chemotherapy should be evaluated carefully before surgery is
      considered.

PMID- 24668309
TI  - Zoledronic acid in combination with alfacalcidol has additive effects on
      trabecular microarchitecture and mechanical properties in osteopenic
      ovariectomized rats.
AB  - BACKGROUND: We conducted the present study to investigate the therapeutic effects
      of the antiresorptive agent zoledronic acid (ZOL), alone and in combination with
      alfacalcidol (ALF), in a rat model of postmenopausal osteoporosis. METHODS:
      Female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age.
      Twelve weeks post surgery, rats were randomized into six groups: (1) sham +
      vehicle, (2) OVX + vehicle, (3) OVX + ZOL (100 MUg/kg, i.v. single dose), (4) OVX
      + ZOL (50 MUg/kg, i.v. single dose), (5) OVX + ALF (0.5 MUg/kg, oral gauge daily)
      and (6) OVX + ZOL (50 MUg/kg, i.v. single dose) + ALF (0.5 MUg/kg, oral gauge
      daily) for 12 weeks. After treatment, we evaluated the mechanical properties of
      the lumbar vertebra and femoral mid-shaft. Femurs were also tested for bone
      density, porosity and trabecular micro-architecture. Biochemical markers in serum
      and urine were also determined. RESULTS: With respect to improvement in the
      mechanical strength of the lumbar spine and the femoral mid-shaft, the
      combination treatment of ZOL and ALF was more effective than each administered as
      a monotherapy. Moreover, combination therapy using ZOL and ALF preserved the
      trabecular micro-architecture and cortical bone porosity. Furthermore, the
      combination treatment of ZOL and ALF corrected the decrease in serum calcium and
      increase in serum alkaline phosphatase and the tartarate-resistant acid
      phosphatase level better than single-drug therapy using ZOL or ALF in OVX rats.
      In addition, the combination treatment of ZOL and ALF corrected the increase in
      urine calcium, phosphorous and creatinine levels better than single-drug therapy
      using ZOL or ALF in OVX rats. CONCLUSIONS: These data suggest that the
      combination treatment of ZOL and ALF has a therapeutic advantage over each
      monotherapy for the treatment of osteoporosis.

PMID- 24668310
TI  - Waist circumference is associated with locomotive syndrome in elderly females.
AB  - BACKGROUND: Central obesity has been proved to be a strong risk factor for
      numerous health-related problems as well as mortality. However, there have been
      no studies on the relationship between central obesity and locomotive syndrome
      (LS). The present study investigated the influence of central obesity on LS.
      METHODS: A total of 217 females between the ages of 60 and 79 years (mean 68.2 +/
      5.0 years) who completed the questionnaires, physical examination and physical
      performance tests in the Yakumo study in 2011-2012 were enrolled in this study.
      Participants were assessed according to the 25-Question Geriatric Locomotive
      Function Scale (GLFS-25), visual analog scale (VAS) for lower back pain (LBP) and
      knee pain, and the Roland Morris Disability Questionnaire (RDQ). LS was defined
      as having a score of >16 points on the GLFS-25. Height, weight, waist
      circumference (WC), hip circumference, % body fat and bone mineral density were
      measured. Body mass index and waist-to-hip ratio were calculated. The timed up
      and-go test, one-leg standing time with eyes open, 10-m gait time and maximum
      stride were assessed. Back muscle strength and grip strength were measured. The
      relationships between obesity-related parameters and GLFS-25, RDQ, VAS and
      physical performance tests were analyzed. RESULTS: The GLFS-25, LBP and knee pain
      showed significant correlation with most of obesity-related parameters. Among
      obesity-related parameters, WC was most strongly related to the GLFS-25, LBP and
      knee pain. When participants were stratified by WC, larger WC was significantly
      associated with a higher GLFS-25 score, higher prevalence of LS and higher VAS
      for LBP and knee pain as well as poorer results in some physical performance
      tests even after adjustment by age. CONCLUSIONS: The present study revealed that
      central obesity is significantly associated with LS, and WC can be a useful
      parameter to assess the risk of LS in elderly women.

PMID- 24668311
TI  - Outcomes and complications of fractures of distal radius (AO type B and C): volar
      plating versus nonoperative treatment.
AB  - OBJECTIVES: Management of AO type B and C fractures of the distal radius is
      controversial. This study compares outcomes and complications of AO type B and C
      fractures of the distal radius treated with volar locked plating and nonoperative
      methods. MATERIALS AND METHODS: Sixty-four patients with fractures of the distal
      radius (AO type B and C) were included in this study, according to inclusion
      criteria, and were allocated to the volar plating group or nonoperative group by
      alternate randomization: 32 patients with odd numbers went into the nonoperative
      group and the other 32 with even numbers went into the volar plating group.
      Patients in the nonoperative group were managed with closed reduction of the
      fracture and plaster cast application under an image intensifier. Those in the
      volar plating group were managed by open reduction and fixation with a volar
      locked plate. Preoperative and postoperative serial clinico-radiological follow
      up was done. The range of movement, grip strength, functional outcome scores and
      radiological parameters were compared. Student's t-test was used for statistical
      analysis with significance at p < 0.05. RESULTS: Range of movement and functional
      scores were significantly (p < 0.001) better in the volar plating group, but the
      difference in ulnar variance and radial and ulnar deviation was insignificant as
      compared to the nonoperative group. At 24 months follow-up, the nonoperative
      group had significantly more cases with malunion, articular incongruity and
      osteoarthritis. CONCLUSION: In cases of AO type B or C fractures of the distal
      radius, volar locked plating provides anatomical stable fixation and early
      mobilization with better clinico-radiological outcome as compared to conservative
      treatment.

PMID- 24668312
TI  - Radiation-induced liver disease as a mimic of liver metastases at serial PET/CT
      during neoadjuvant chemoradiation of distal esophageal cancer.
AB  - PURPOSE: To determine the frequency and appearance of radiation-induced liver
      disease on PET/CT in patients undergoing serial imaging during neoadjuvant
      chemoradiation of distal esophageal cancer. MATERIALS AND METHODS: In this IRB
      approved, HIPAA-compliant retrospective analysis, we identified 112 patients with
      distal esophageal cancer treated by neoadjuvant chemoradiation who had serial
      PET/CT imaging available for review. Two readers reviewed all studies in
      consensus and recorded those cases where new foci of visually detectable
      increased FDG avidity appeared in the liver during therapy. The etiology of such
      foci was determined from corresponding findings at CT or MRI, by hepatic biopsy
      during surgery, by characteristic evolution on post-operative imaging, or by a
      combination of these methods. RESULTS: New foci of FDG avidity developed in the
      liver during neoadjuvant therapy in 10 of 112 (9%) patients, of whom nine (8%)
      were determined to have radiation-induced liver disease based on further imaging
      and/or biopsy and one of whom had developed interval metastatic disease based on
      biopsy. In the cases of radiation-induced liver disease, the abnormal foci were
      found only in the caudate and left hepatic lobes, near the primary tumor, while
      the patient who developed interval metastatic disease had involvement of the
      inferior right hepatic lobe, remote from the radiation therapy field. CONCLUSION:
      New foci of increased FDG avidity are commonly seen in the caudate and left
      hepatic lobes of the liver during neoadjuvant chemoradiation of distal esophageal
      cancer, and these findings generally reflect radiation-induced liver disease
      rather than metastatic disease.

PMID- 24668313
TI  - Dendrimer-surfactant interactions.
AB  - In this article, we reviewed the interactions between dendrimers and surfactants
      with particular focus on the interaction mechanisms and physicochemical
      properties of the yielding dendrimer-surfactant aggregates. In order to provide
      insight into the behavior of dendrimers in biological systems, the interactions
      of dendrimers with bio-surfactants such as phospholipids in bulk solutions, in
      solid-supported bilayers and at the interface of phases or solid-states were
      discussed. Applications of the dendrimer-surfactant aggregates as templates to
      guide the synthesis of nanoparticles and in drug or gene delivery were also
      mentioned. 

PMID- 24668314
TI  - Use of near infrared spectroscopy to detect impaired tissue oxygen saturation in
      patients with complex regional pain syndrome type 1.
AB  - PURPOSE: Deep tissue hypoxia has been hypothesized in the pathogenesis of complex
      regional pain syndrome type 1 (CRPS 1) for some patients. The purpose of this
      study was to determine if near-infrared spectroscopy (NIRS) could detect
      differences in deep tissue oxygen saturation (StO2) and microcirculatory function
      in the hands of patients with CRPS 1. METHODS: Tissue oxygen saturation was
      evaluated at baseline and during an ischemia reperfusion challenge using vascular
      occlusion testing (VOT) in affected vs unaffected hands of patients with
      unilateral upper limb CRPS 1. A non-randomized experimental study design was used
      with baseline StO2 as the primary outcome measure. Secondary outcome measures
      were occlusion and reperfusion slopes from VOT. Values were compared with the
      unaffected, contralateral hand and with the dominant and non-dominant hands of
      sex and age-matched volunteers. Correlations between values derived from NIRS and
      measures of pain and function from the Brief Pain Inventory (BPI) and the
      Disability of the Arm, Shoulder and Hand (DASH) questionnaires were explored.
      RESULTS: Independent of handedness, the baseline StO2 of the affected hands of
      ten CRPS 1 patients was significantly lower than that of their unaffected hands (
      5.8%; 95% confidence interval [CI] -10.6 to -1.0; P = 0.02). The baseline StO2 of
      affected CRPS 1 hands was also significantly lower than the non-dominant hands of
      ten volunteers (-7.3%; 95% CI -12.4 to -2.3; P = 0.007). Differences in VOT
      occlusion and reperfusion slopes did not reveal changes that could be uniquely
      attributed to CRPS 1. No significant correlations were detected between values
      derived from VOT and values for pain and function obtained from BPI and DASH
      questionnaires for patients with CRPS 1. CONCLUSIONS: Hands of patients affected
      by CRPS 1 of the upper limb showed significantly lower StO2 compared with their
      unaffected contralateral hand as well as the hands of control subjects. This
      trial was registered at: ClinicalTrials.gov: NCT01586377.

PMID- 24668315
TI  - A randomized placebo-controlled trial of two doses of pregabalin for
      postoperative analgesia in patients undergoing abdominal hysterectomy.
AB  - PURPOSE: Acute pain after open abdominal hysterectomy limits the function of
      patients in the postoperative period, but data regarding the analgesic efficacy
      of a low dose of pregabalin (75 or 150 mg) have been conflicting. This study was
      performed to determine if a low dose of pregabalin could decrease postoperative
      opioid use following abdominal hysterectomy when compared with placebo. METHODS:
      American Society of Anesthesiologists I-II patients older than 18 yr and
      scheduled for open elective abdominal hysterectomy were recruited for
      participation and randomized to one of three groups: pregabalin 75 mg (P75),
      pregabalin 150 mg (P150), or placebo. The study drug was administered two hours
      prior to surgery and 12 hr following the initial dose. Anesthetic technique and
      postoperative analgesia were standardized. Postoperative pain was managed using
      patient-controlled analgesia with morphine. Pain at rest and movement as well as
      nausea were assessed with an 11-point numeric rating scale. RESULTS: One hundred
      and one patients were recruited, and 89 patients completed the study. Mean (SD)
      cumulative morphine consumption at 24 hr postoperatively was 54.0 (26.2) mg for
      the placebo group, 53.1 (22.7) mg for the P75 group, and 44.3 (20.9) mg for the
      P150 group. Independent Student's t tests indicated no difference between the
      placebo group and either the P75 group (95% confidence interval [CI]: -11.75 to
      13.44; P = 0.8937) or the P150 group (95% CI: -2.74 to 22.15; P = 0.1238).
      CONCLUSIONS: At the doses used in this study, pregabalin treatment may not be
      effective in reducing opioid use up to 24 hr postoperatively following abdominal
      hysterectomy. This trial was registered at www.ClinicalTrials.gov : NCT00781131.

PMID- 24668316
TI  - Health and safety implications of recruitment payments in migrant construction
      workers.
AB  - BACKGROUND: The Middle East construction sector is heavily reliant on a migrant
      workforce that predominantly originates from South Asia. It is common practice
      for migrant construction workers to pay a local labour recruiter the equivalent
      of one or more years' prospective overseas salary to secure employment, work and
      travel permits and transportation. The occupational health and safety
      implications of these financial arrangements remain unexplored. AIMS: To examine
      associations between payment to a labour recruiter, perceived general health and
      worksite accidents among migrant construction workers in the Middle East.
      METHODS: A questionnaire was completed by a convenience sample of predominantly
      Indian migrant construction workers drawn from a large construction project. The
      relationship between payment and risk of poor health and workplace accidents was
      assessed using multivariate logistic regression models (crude and adjusted for
      socio-demographic and occupational factors). RESULTS: There were 651
      participants. The majority (58%) of migrant construction workers had paid a
      labour recruiter and ~40% had experienced a worksite accident. Between 3%
      (labourers) and 9% (foremen) perceived their health to be poor. Labourers and
      skilled workers who had paid a labour recruiter were significantly more likely to
      have experienced a worksite accident in the previous 12 months. Skilled workers,
      but not labourers and foremen, who had paid a labour recruiter were at increased
      risk of poor health. CONCLUSIONS: The mechanisms linking labour recruiter
      payments to adverse safety and health outcomes warrant investigation with a view
      to developing interventions to erode these links.

PMID- 24668318
TI  - Healthe Kids: an assessment of program performance and participation.
AB  - Many states in the United States have mandated school health screenings for early
      identification and referral to professional services for a set of health
      conditions. Healthe Kids, a community-based program, began offering school-based
      health screenings to Missouri elementary schools in March 2007. The purpose of
      the article is to provide a description of the Healthe Kids program, including
      the team members, screening process, and the program's underlying technology.
      Further, we present data gathered during the first 5 years of the Healthe Kids
      program in Kansas City, Missouri, and describe improvements to the program from
      lessons learned and implications to school nurses and health care delivery. 

PMID- 24668319
TI  - [Dermoscopy of nails].
AB  - Pigmented and nonpigmented nail abnormalities often represent a challenge for
      clinicians because many, and sometimes potentially life-threatening differential
      diagnoses must be taken into consideration. Although many details of nail
      diseases can already be assessed with the naked eye, dermoscopy opens up a second
      microscopic level of inspection, which can be very useful for the diagnostic
      process. In the last 20 years dermoscopy has made rapid progress in the further
      development of criteria for the early recognition of melanoma. In addition, the
      use of dermoscopy has been extended to the examination of cutaneous adnexa, such
      as hairs (trichoscopy) and nails (onychoscopy). Many, sometimes highly specific
      criteria for the dermoscopic assessment of nail diseases have been described in a
      series of recently published articles. This review article provides important
      diagnostic aids for a well-founded dermoscopic assessment of nail diseases.

PMID- 24668320
TI  - Colon cancer with metachronous presentation of Krukenberg's tumor in an
      adolescent.

PMID- 24668321
TI  - Using AFM to probe the complexation of DNA with anionic lipids mediated by
      Ca(2+): the role of surface pressure.
AB  - Complexation of DNA with lipids is currently being developed as an alternative to
      classical vectors based on viruses. Most of the research to date focuses on
      cationic lipids owing to their spontaneous complexation with DNA. Nonetheless,
      recent investigations have revealed that cationic lipids induce a large number of
      adverse effects on DNA delivery. Precisely, the lower cytotoxicity of anionic
      lipids accounts for their use as a promising alternative. However, the
      complexation of DNA with anionic lipids (mediated by cations) is still in early
      stages and is not yet well understood. In order to explore the molecular
      mechanisms underlying the complexation of anionic lipids and DNA we proposed a
      combined methodology based on the surface pressure-area isotherms, Gibbs
      elasticity and Atomic Force Microscopy (AFM). These techniques allow elucidation
      of the role of the surface pressure in the complexation and visualization of the
      interfacial aggregates for the first time. We demonstrate that the DNA complexes
      with negatively charged model monolayers (DPPC/DPPS 4 : 1) only in the presence
      of Ca(2+), but is expelled at very high surface pressures. Also, according to the
      Gibbs elasticity plot, the complexation of lipids and DNA implies a whole
      fluidisation of the monolayer and a completely different phase transition map in
      the presence of DNA and Ca(2+). AFM imaging allows identification for the first
      time of specific morphologies associated with different packing densities. At low
      surface coverage, a branched net like structure is observed whereas at high
      surface pressure fibers formed of interfacial aggregates appear. In summary,
      Ca(2+) mediates the interaction between DNA and negatively charged lipids and
      also the conformation of the ternary system depends on the surface pressure. Such
      observations are important new generic features of the interaction between DNA
      and anionic lipids. 

PMID- 24668322
TI  - Reactivity studies of a soluble LiH-complex and non-spectator behaviour of its
      stabilising phosphinoamide ligand.
AB  - We have investigated and compared the reactivity of the phosphinoamide stabilized
      hydrocarbon-soluble LiH complex [(LLi)4(LiH)4] 1 (L = [Ph2PNDip], Dip = 2,6
      (i)Pr2C6H3) and the lithium phosphinoamide [LLi] 2 towards some unsaturated
      organic substrates. The complexes [(LSiMe2OLi)2(HDCCLi)2] 3 (DCC = CyNCNCy, Cy =
      cyclohexyl) and [(HDCC)6Li8O] 4 were obtained from reactions of 1 with DCC, and
      the complexes [{LN(Ph)N(Ph)Li}2] 5 and [{PhN(Li)-N(Li)Ph}4] 7 were obtained from
      reactions of 1 with azobenzene. Complex 5 was furthermore obtained in good yield
      from 2 and azobenzene, and was converted to the solvate [LN(Ph)N(Ph)Li(THF)] 6.
      Complex 7 could be independently synthesized from lithium metal and azobenzene.
      Complex 1 undergoes hydrolithiation reactions with some substrates, as evidenced
      by the formation of complexes 3, 4, and indirectly by 7, but also takes part in
      addition reactions of the stabilizing phosphinoamide ligand onto substrates as
      shown by the isolation of complexes 3 and 5. The crystal structures of complexes
      3, 5, 6, 7 and [LLi(THF)3] are reported. 

PMID- 24668323
TI  - Optical properties of PbS nanocrystal quantum dots at ambient and elevated
      pressure.
AB  - We investigated pressure-dependent changes in the optical properties of PbS
      nanocrystal quantum dots (NQD) by combining X-ray scattering and optical
      absorption spectroscopy in a diamond anvil cell. We discovered that the excitonic
      absorption peak vanishes as the NQD crystal structure reversibly undergoes the
      pressure-induced phase transition from rock-salt to orthorhombic structure. In
      the rock-salt phase, the pressure coefficient ?E(g)/?P of PbS NQD is negative and
      decreases in magnitude with decreasing NQD size. The basic theoretical model
      based on literature values of the PbS bulk modulus significantly overestimated
      the change in pressure coefficient with NQD size. We present a model that
      includes the size-dependence of both the pressure coefficient and bulk modulus to
      describe the experimentally observed optical and structural trends.

PMID- 24668324
TI  - Microfluidics-assisted rapid generation of tubular cell-laden microgel inside
      glass capillaries.
AB  - Drug screening using engineered blood vessels (EBVs) faces considerable barriers
      in approximating the conditions of an in vivo environment. To address this issue,
      we have introduced a microfluidic system for cell-laden tubular microgels. N
      Carboxyethyl chitosan crosslinked with oxidized dextran was used for in situ
      gelable tubular scaffolds. The microfluidic system consisted of four glass
      capillaries that generated a coaxial flow of pre-polymer and phosphate buffered
      solutions. It rapidly produced cell-laden tubular microgels inside glass
      capillaries. The mechanical strength of the tubular microgels was suitable for
      their application as EBVs, with a maximum Young's modulus of 12.2 +/- 1.9 kPa. In
      vitro cell studies using human umbilical vein endothelial cells verified the
      biocompatibility and non-cytotoxicity of the gelation and fabrication process.
      Thus, in situ gelable cell-laden tubular microgels can be a potential platform
      for screening drugs to treat blood vessel diseases. 

PMID- 24668325
TI  - The role of high-quality friendships in female adolescents' eating pathology and
      body dissatisfaction.
AB  - PURPOSE: Peers may serve as risk factors for body dissatisfaction and eating
      pathology through two possible routes: (1) promoting body dissatisfaction through
      appearance-related interactions (e.g. weight-teasing); (2) a non-specific social
      support route whereby poor quality peer relations result in depression and
      consequently eating pathology. The second route has received little attention
      and, therefore, was the focus of this study. METHODS: A cross-sectional study in
      which 216 adolescent girls (aged 13-16 years) completed self-report measures of
      positive and negative friendship qualities, friendship functions, eating
      pathology, body dissatisfaction and depression. RESULTS: Those reporting poorer
      quality friendships tended to show greater eating pathology and greater body
      dissatisfaction. These associations were reduced to non-significance when
      covarying depression. There was no evidence that the role of friendships was
      moderated by the extent to which participants valued close relations.
      CONCLUSIONS: Low-quality friendships are associated with disordered eating and
      may be suitable targets for prevention.

PMID- 24668326
TI  - Effect of respiration on Korotkoff sounds and oscillometric cuff pressure pulses
      during blood pressure measurement.
AB  - Blood pressure (BP) measurement accuracy depends on consistent changes in
      Korotkoff sounds (KorS) for manual measurement and oscillometric pulses for
      automated measurement, yet little is known about the direct effect of respiration
      on these physiological signals. The aim of this research was to quantitatively
      assess the modulation effect of respiration on Korotkoff sounds and oscillometric
      pulses. Systolic and diastolic blood pressures were measured manually from 30
      healthy subjects (age 41 +/- 12 years). Three static cuff pressure conditions
      were studied for two respiratory rates. Cuff pressure [with oscillometric pulses
      (OscP)], ECG, chest motion respiration [respiration signal (Resp), from
      magnetometer] and Korotkoff sounds (KorS, from digital stethoscope) were recorded
      twice for 20 s. The physiological data were evenly resampled. Respiratory
      frequency was calculated from Resp (fR), OscP (fO) and KorS (fK) from peak
      spectral frequency. There was no statistically significant difference between fR
      and fO or fK. Respiratory modulation was observed in all subjects. OscP amplitude
      modulation changed significantly between the two respiratory rates (p < 0.05) and
      between the three cuff pressures (p < 0.0001), and decreased significantly with
      decreasing cuff pressure (p < 0.05). The phase shift between Resp and modulation
      of OscP was statistically significant with respiratory rates (p < 0.05), but not
      with cuff pressures. It is accepted that BP in individuals is variable and that
      this relates to respiration; we now show that this respiration modulates
      oscillometric pulse and Korotkoff sound amplitudes from which BP is measured. 

PMID- 24668328
TI  - Determination of prognostic factors in Japanese patients with advanced gastric
      cancer using the data from a randomized controlled trial, Japan clinical oncology
      group 9912.
AB  - BACKGROUND: In advanced gastric cancer (AGC), no globally accepted prognostic
      scoring system has been developed. Therefore, we explored baseline prognostic
      factors in Japanese AGC patients using the data from a randomized controlled
      trial, Japan Clinical Oncology Group (JCOG) 9912, which investigated the efficacy
      of systemic chemotherapy as a first-line treatment. PATIENTS AND METHODS:
      Prognostic factors and prognostic indices for overall survival were screened and
      evaluated in patients enrolled in JCOG9912 using the Cox proportional hazard
      model. The Royal Marsden Hospital prognostic model was also applied to the
      JCOG9912 trial. RESULTS: A total of 650 (92.3%) of the 704 patients randomized in
      the JCOG9912 trial, for whom complete data were available for multivariate
      analyses, was included in the present study (5-fluorouracil arm, n = 215;
      irinotecan plus cisplatin arm, n = 216; S-1 arm, n = 219). The median survival
      time (MST) for all patients was 11.8 months. To construct a prognostic index, we
      selected four risk factors by multivariate analysis: performance status >= 1,
      number of metastatic sites >= 2, no prior gastrectomy, and elevated alkaline
      phosphatase. MSTs were 17.0 months for patients categorized into the low-risk
      group, who had zero or one risk factor (n = 225); 10.4 months for patients in the
      moderate-risk group, who had two or three risk factors (n = 368); and 5.0 months
      for patients in the high-risk group, who had all four risk factors (n = 57).
      CONCLUSION: In the present study, we propose a new prognostic index for patients
      with AGC. This can be used for more appropriate patient stratification in future
      clinical trials.

PMID- 24668329
TI  - Clinical trial results: a clinical trial bazaar!

PMID- 24668327
TI  - Incidence of mucositis in patients treated with temsirolimus-based regimens and
      correlation to treatment response.

PMID- 24668330
TI  - Squamous cell carcinoma of the oral cavity in a woman with a 9-year history of
      ovarian cancer: is exposure to pegylated liposomal Doxorubicin a factor?

PMID- 24668331
TI  - The European medicines agency review of bosutinib for the treatment of adult
      patients with chronic myelogenous leukemia: summary of the scientific assessment
      of the committee for medicinal products for human use.
AB  - On March 27, 2013, a conditional marketing authorization valid throughout the
      European Union was issued for bosutinib (Bosulif) for the treatment of adult
      patients with chronic-phase, accelerated-phase, and blast-phase Philadelphia
      chromosome positive (Ph+) chronic myelogenous leukemia (CML) previously treated
      with one tyrosine kinase inhibitor or more and for whom imatinib, nilotinib, and
      dasatinib are not considered appropriate treatment options. Bosutinib is a kinase
      inhibitor that targets the BCR-ABL kinase. The recommended dose is 500 mg of
      bosutinib once daily. The main evidence of efficacy for bosutinib was based on a
      CML subgroup analysis of study 3160A4-200, a phase I/II study of bosutinib in Ph+
      leukemia in imatinib-resistant or intolerant CML. The subgroup was defined based
      on the presence of a BCR-ABL kinase domain mutation that would be expected to
      confer resistance to dasatinib (F317, E255) or nilotinib (E255, Y253, F359) and
      expected to have sensitivity to bosutinib or based on the presence of medical
      conditions or prior toxicities that may predispose the patient to unacceptable
      risk in the setting of nilotinib or dasatinib therapy. A conditional marketing
      authorization was granted because of the limited evidence of efficacy and safety
      currently supporting this last-line indication.

PMID- 24668332
TI  - Learning from gus.

PMID- 24668333
TI  - Self-reported financial burden and satisfaction with care among patients with
      cancer.
AB  - BACKGROUND: Health care-related costs and satisfaction are compelling targets for
      quality improvement in cancer care delivery; however, little is known about how
      financial burden affects patient satisfaction. METHODS: This was an
      observational, cross-sectional, survey-based study assessing patient-reported
      financial burden (FB). Eligible patients were >= 21 years with solid tumor
      malignancy and were receiving chemotherapy or hormonal therapy for >= 1 month.
      The Patient Satisfaction Questionnaire Short-Form assessed patient satisfaction
      with health care. Subjective FB related to cancer treatment was measured on a 5
      point Likert scale. RESULTS: Of 174 participants (32% response rate), 47%
      reported significant/catastrophic FB. Participants reported highest satisfaction
      with interpersonal manner and lowest satisfaction with financial aspects of care.
      In adjusted analysis, high FB was negatively associated with general satisfaction
      (coefficient: -.29), satisfaction with technical quality (coefficient: -.26), and
      satisfaction with financial aspects of care (coefficient: -.62). Older age was
      associated with higher scores in all satisfaction subscales except patient
      physician communication and financial aspects. Annual household income of
      <$20,000 was associated with lower satisfaction scores in all subscales except
      time spent with doctor. High FB was not associated with patient satisfaction
      scores for accessibility and convenience, communication, interpersonal manner, or
      time spent with doctor. CONCLUSION: FB is a potentially modifiable correlate of
      poor satisfaction with cancer care including general satisfaction and
      satisfaction with the technical quality of care. Addressing cancer-associated FB
      may lead to improved satisfaction, which in turn can influence adherence,
      outcomes, and quality of life.

PMID- 24668334
TI  - Cervical cancer-related knowledge, attitudes, and practices of health
      professionals working in brazil's network of primary care units.
AB  - INTRODUCTION: Brazil's national strategy for cervical cancer screening includes
      using the Papanicolaou (Pap) test every 3 years among women aged 25-64 years.
      Comprehensive primary care services are provided through a network of primary
      health units, but little is known about cervical cancer-related knowledge,
      attitudes, and practices among health professionals and coordinators working in
      these facilities. METHODS: In 2011, we conducted a cross-sectional nationally
      representative phone survey of 1,600 primary health care units to interview one
      unit coordinator and one health care professional per unit (either nurse,
      physician, or community health worker). Responses were obtained from 1,251
      coordinators, 182 physicians, 347 nurses, and 273 community health workers.
      Questionnaires were administered to assess health units' characteristics and
      capacity for cervical cancer-related services as well as health professionals'
      perceived effectiveness of the Pap test, preparedness to talk to women about
      cervical cancer, adherence with screening guidelines, and willingness to
      recommend human papillomavirus (HPV) vaccination to females. RESULTS: Most units
      conducted screening (91.9%), used home visits to conduct recruitment and outreach
      (83.4%), and provided follow-up to women who did not return to discuss Pap test
      results (88.1%). Approximately 93% of health professionals stated that Pap
      testing was effective in decreasing death rates from cervical cancer and 65%
      stated that national guidelines for cervical cancer screening are very
      influential; 93% of nurses and physicians reported screening women annually and
      75% reported beginning to screen women younger than 25 years old. Regarding HPV
      vaccination, almost 90% of nurses and physicians would recommend the HPV vaccine
      to their females patients if it were available. A larger proportion of physicians
      and nurses recommended the HPV vaccine to older girls (13-18 years) and women (19
      26 years and even older than 26 years) than to younger girls (12 years or
      younger). CONCLUSION: Although Brazil's network of primary care units has
      significantly increased access to cervical cancer screening, effective strategies
      are needed to ensure that women get screened at the appropriate ages and
      intervals. Additionally, this study's baseline data on HPV vaccination may be
      useful as Brazil embarks on a national HPV vaccination program in 2014.

PMID- 24668335
TI  - Current cervical cancer screening knowledge, awareness, and practices among U.S.
      affiliated pacific island providers: opportunities and challenges.
AB  - BACKGROUND: Cervical cancer is a leading cause of cancer mortality in nearly all
      U.S. Affiliated Pacific Island Jurisdictions (USAPIJ); however, most
      jurisdictions are financially and geographically limited in their capacity to
      deliver routine screening. METHODS: We conducted a cross-sectional survey of 72
      health care providers from five of the six USAPIJ in 2011 to assess knowledge,
      beliefs, practices, and perceived barriers regarding routine cervical cancer
      screening. We compared the responses of providers from jurisdictions that were
      funded by the Centers for Disease Control and Prevention's National Breast and
      Cervical Cancer Early Detection Program (NBCCEDP) with those that were not
      funded. RESULTS: Most providers reported cervical cancer prevention as a priority
      in their clinical practices (90.3%) and use the Papanicolaou test for screening
      (86.1%). Many providers reported knowledge of screening guidelines (76.4%);
      however, more than half reported that annual screening is most effective (56.9%).
      Providers in non-NBCCEDP-funded jurisdictions reported greater acceptance of
      visual inspection with acetic acid (93.9%) and self-sampling for human
      papillomavirus testing (48.5%) compared with NBCCEDP-funded jurisdictions (15.4%
      and 30.8% respectively). Providers from non-NBCCEDP-funded jurisdictions reported
      inadequate technological resources for screening women (42.4%), and approximately
      25% of providers in both groups believed that screening was cost-prohibitive.
      CONCLUSION: Although cervical cancer screening is a priority in clinical
      practice, beliefs about annual screening, costs associated with screening, and
      varying levels of support for alternative screening tests pose barriers to
      providers throughout the USAPIJ. Further exploration of using evidence-based,
      lower cost, and sustainable screening technologies is warranted in addition to
      emphasizing timely follow-up of all positive cases.

PMID- 24668336
TI  - Feasibility of conducting long-term follow-up of children and infants treated for
      CNS tumors on the same cooperative group clinical trial protocol.
AB  - Given the barriers to conducting long-term assessment of neurocognitive and
      psychosocial functioning of those treated in infancy for central nervous system
      (CNS) tumors, a multi-site feasibility study was conducted. The primary objective
      was to demonstrate that it is feasible to identify, locate and assess the
      functioning of children treated on the same protocol 10-years post-treatment. Six
      sites obtained institutional approval, identified and recruited subjects, and
      obtained comprehensive neurocognitive and psychosocial data. All feasibility
      objectives were met. Barriers to participation included length of time for
      Institutional Review Board submission and review, clinical demands, limited
      eligible participants at individual institutions, difficulty locating long-term
      subjects and stipend/reimbursement concerns. Results indicate that long-term
      studies are feasible and essential given the need to address long-term issues of
      children treated at a young age for CNS tumors, especially as they relate to
      later academic and vocational planning, but require significant coordination and
      commitment of cooperative group and institutional resources.

PMID- 24668337
TI  - Dinuclear zinc(II) complexes containing (benzimidazol-2-yl)benzene that overcome
      drug resistance in hepatocellular carcinoma cells through induction of
      mitochondria fragmentation.
AB  - Herein we demonstrated that dinuclear zinc complexes could overcome drug
      resistance in R-HepG2 drug resistance hepatocellular carcinoma cells through
      induction of mitochondria-mediated apoptosis or by triggering mitochondria
      fragmentation, depletion of the membrane potential and intracellular ATP levels. 

PMID- 24668338
TI  - Pregnancy and drug use in neurological disease.

PMID- 24668339
TI  - MR image mimicking the "eye of the tiger" sign in Wilson's disease.

PMID- 24668340
TI  - Synthesis of alpha-tribromomethylamines via Mg-mediated addition of bromoform to
      imines.
AB  - Mg-mediated addition of bromoform to electron deficient imines such as N
      sulfonylimines affords alpha-tribromomethylated N-sulfonylamines in good to
      excellent yields. The procedure could be further simplified by transforming the
      imine precursors, alpha-sulfonyl-N-tosyl- and Boc-amines, in one pot to the
      corresponding alpha-tribromomethyl derivatives. Facile removal of the Boc
      protecting group in nearly quantitative yield and a silver carbonate mediated
      monodebromination have also been demonstrated. 

PMID- 24668341
TI  - Duration of antibiotic treatment after appendicectomy for acute complicated
      appendicitis.
AB  - BACKGROUND: Antibiotic treatment after appendicectomy for complicated
      appendicitis aims to reduce postoperative infections. However, available data on
      the duration of treatment are limited. This study compared the difference in
      infectious complications between two protocols, involving either 3 or 5 days of
      postoperative antibiotic treatment. METHODS: This was an observational cohort
      study of all adult patients who had an appendicectomy between January 2004 and
      December 2010 at either one of two hospitals in the same region. At location A,
      the protocol included 3 days of postoperative antibiotic treatment, whereas at
      location B it specified 5 days. The primary outcome was the development of
      postoperative infections as either superficial wound infection or deep intra
      abdominal infections. RESULTS: A total of 1143 patients with acute appendicitis
      underwent appendicectomy, of whom 267 (23.4 per cent) had complicated
      appendicitis. The duration of postoperative antibiotic treatment was 3 days in
      135 patients (50.6 per cent) and at least 5 days in 123 (46.1 per cent). No
      difference was found between antibiotic treatment for 3 or 5 days in terms of
      developing an intra-abdominal abscess (odds ratio (OR) 1.77, 95 per cent
      confidence interval 0.68 to 4.58; P = 0.242) or a wound infection (OR 2.74, 0.54
      to 13.80; P = 0.223). In patients with complicated appendicitis, the laparoscopic
      approach was identified as a risk factor for developing an intra-abdominal
      abscess in univariable analysis (OR 2.46, 1.00 to 6.04; P = 0.049), but was not
      confirmed as an independent risk factor for this complication in multivariable
      analysis (OR 2.32, 0.75 to 7.14; P = 0.144). CONCLUSION: After appendicectomy for
      complicated appendicitis, 3 days of antibiotic treatment is equally effective as
      5 days in reducing postoperative infections.

PMID- 24668342
TI  - BAMS2 workspace: a comprehensive and versatile neuroinformatic platform for
      collating and processing neuroanatomical connections.
AB  - We describe a novel neuroinformatic platform, the BAMS2 Workspace
      (http://brancusi1.usc.edu), designed for storing and processing information on
      gray matter region axonal connections. This de novo constructed module allows
      registered users to collate their data directly by using a simple and versatile
      visual interface. It also allows construction and analysis of sets of connections
      associated with gray matter region nomenclatures from any designated species. The
      Workspace includes a set of tools allowing the display of data in matrix and
      networks formats and the uploading of processed information in visual, PDF, CSV,
      and Excel formats. Finally, the Workspace can be accessed anonymously by third
      party systems to create individualized connectivity networks. All features of the
      BAMS2 Workspace are described in detail and are demonstrated with connectivity
      reports collated in BAMS and associated with the rat sensory-motor cortex, medial
      frontal cortex, and amygdalar regions.

PMID- 24668344
TI  - Fracture behavior of metal-ceramic fixed dental prostheses with frameworks from
      cast or a newly developed sintered cobalt-chromium alloy.
AB  - OBJECTIVES: The aim of this study was to investigate the fracture behavior of
      metal-ceramic bridges with frameworks from cobalt-chromium-molybdenum (CoCrMo),
      which are manufactured using conventional casting or a new computer-aided
      design/computer-aided manufacturing (CAD/CAM) milling and sintering technique.
      MATERIALS AND METHODS: A total of 32 metal-ceramic fixed dental prostheses
      (FDPs), which are based on a nonprecious metal framework, was produced using a
      conventional casting process (n = 16) or a new CAD/CAM milling and sintering
      process (n = 16). Eight unveneered frameworks were manufactured using each of the
      techniques. After thermal and mechanical aging of half of the restorations, all
      samples were subjected to a static loading test in a universal testing machine,
      in which acoustic emission monitoring was performed. Three different critical
      forces were revealed: the fracture force (F max), the force at the first
      reduction in force (F decr1), and the force at the critical acoustic event (F
      acoust1). RESULTS: With the exception of the veneered restorations with cast or
      sintered metal frameworks without artificial aging, which presented a
      statistically significant but slightly different F max, no statistically
      significant differences between cast and CAD/CAM sintered and milled FDPs were
      detected. Thermal and mechanical loading did not significantly affect the
      resulting forces. CONCLUSIONS: Cast and CAD/CAM milled and sintered metal-ceramic
      bridges were determined to be comparable with respect to the fracture behavior.
      CLINICAL SIGNIFICANCE: FDPs based on CAD/CAM milled and sintered frameworks may
      be an applicable and less technique-sensitive alternative to frameworks that are
      based on conventionally cast frameworks.

PMID- 24668343
TI  - In vitro effects of bisphosphonates on chemotaxis, phagocytosis, and oxidative
      burst of neutrophil granulocytes.
AB  - OBJECTIVES: Bisphosphonate-associated osteonecrosis of the jaws is a serious side
      effect that mainly occurs in patients receiving highly potent, nitrogen
      containing bisphosphonates. Usually the diagnosis is made due to exposed bone and
      a nonhealing wound. Neutrophil granulocytes are essential for sufficient wound
      healing; therefore, the influence of different bisphosphonates on neutrophil
      granulocytes was the focus of this study. MATERIAL AND METHODS: The effect of
      nitrogen-containing bisphosphonates (ibandronate, pamidronate, and zoledronate)
      and one non-nitrogen-containing bisphosphonate (clodronate) on chemotaxis,
      phagocytosis, and oxidative burst of neutrophil granulocytes in human whole blood
      was analyzed using standard cytometric flow assays. RESULTS: Chemotaxis of
      neutrophils was reduced by almost 50 % when cells were treated with ibandronate
      and zoledronate. All tested nitrogen-containing bisphosphonates moderately
      increased the percentage of phagocytizing neutrophils, whereas the percentage of
      oxidizing cells was extremely affected. Zoledronate increased the oxidative burst
      activity even at low concentrations. Treatment with ibandronate and pamidronate
      reached the same level, but only in at least 10 times the higher concentrations.
      The maximal burst activity of a single cell reached nearly 150 % compared to
      control. In this case, zoledronate also caused maximal effects even at low
      concentrations. Clodronate did not show any effects. CONCLUSION: The results show
      a proinflammatory effect of the nitrogen-containing effect on neutrophil
      granulocytes which might contribute to the development of osteonecrosis. CLINICAL
      RELEVANCE: The altered neutrophil defense might play a key role in the
      pathogenesis of bisphosphonate-associated osteonecrosis of the jaws, although the
      underlying causation between inflammatory reaction and the development of
      necrosis is yet unknown.

PMID- 24668345
TI  - Three-dimensional evaluation of the different donor sites of the mandible for
      autologous bone grafts.
AB  - OBJECTIVES: For effective placement of endosseous implants, a sufficient volume
      of bone is required at the recipient site. The aim of this study is to evaluate
      the density and maximum amount of harvestable bone graft required from the
      mandible symphysis, coronoid process, and ascending ramus, depending on
      dentition. MATERIALS AND METHODS: CT data from 42 patients (13 females and 29
      males) in DICOM format were read using special planning software. Three different
      virtual bone grafts were created, and the dimension outcomes, surface, volume,
      and density were measured in a dentate group (n = 22) and a total edentulous
      group (n = 20). RESULTS: Comparisons between corresponding bone grafts showed no
      difference for the symphysis and coronoid process in relation to dentition, and
      no difference in bone density was observed. However, significant changes between
      the average values of the ramus were found between the two groups (p < 0.0001).
      CONCLUSIONS: Appropriate software and CT data can deliver more accurate
      examinations of the mandible in relation to potential donor sites. Atrophy
      primarily affects the ascending ramus; the symphysis and coronoid process are
      only slightly influenced. CLINICAL RELEVANCE: Using appropriate software in
      conjunction with implant planning, it is possible to analyze potential donor
      areas within the jaw and create virtual bone grafts.

PMID- 24668346
TI  - Structural and redox requirements for the action of anti-diabetic vanadium
      compounds.
AB  - This study presents the first systematic investigation of the anti-diabetic
      properties of non-oxido V(IV) complexes. In particular, the insulin-mimetic
      activity of [V(IV)(taci)2](4+), [V(IV)(inoH-3)2](2-), [V(IV)(dhab)2],
      [V(IV)(hyph(Ph))2], [V(IV)(cat)3](2-) and [V(IV)(pdbh)2]--where taci is 1,3,5
      triamino-1,3,5-trideoxy-cis-inositol, ino is cis-inositol, H2dhab is 2,2'
      dihydroxyazobenzene, H2hyph(Ph) is 3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazole,
      H2cat is catechol and H2pdbh is pentan-2,4-dione benzoylhydrazone--was evaluated
      in terms of free fatty acid (FFA) release. Among the six compounds examined, only
      [V(IV)(pdbh)2], [V(IV)(cat)3](2-) and [V(IV)(hyph(Ph))2], which at the
      physiological pH convert to the corresponding V(IV)O complexes, were found to
      exhibit a significant insulin-mimetic activity compared to VOSO4. In contrast,
      [V(taci)2](4+), [V(inoH-3)2](2-) and [V(dhab)2], which at pH 7.4 keep their
      'bare' non-oxido structure, did not cause any inhibition of FFA. The results,
      therefore, suggest that a V(IV)O functionality is necessary for vanadium
      complexes to exhibit anti-diabetic effects. This agrees with the notion that the
      biotransformations of V compounds in the organism are more important than the
      nature of the species.

PMID- 24668347
TI  - Frictional properties of a polycationic brush.
AB  - The frictional behaviour of end-grafted poly[2-(dimethyl amino)ethyl
      methacrylate] films (brushes) has been shown by friction force microscopy to be a
      strong function of pH in aqueous solution. Data were acquired using bare silicon
      nitride and gold-coated tips, and gold coated probes that were functionalized by
      the deposition of self-assembled monolayers. At the extremes of pH (pH = 1, 2,
      and 12), the friction-load relationship was found to be linear, in agreement with
      Amontons' law of macroscopic friction. However, at intermediate pH values, the
      data were fitted by single asperity contact mechanics models; both Johnson
      Kendall-Roberts (JKR) and Derjaguin-Muller-Toporov models were observed, with JKR
      behaviour fitting the data better at relatively neutral pH. 

PMID- 24668349
TI  - Moving forward.

PMID- 24668350
TI  - Surgical management of lumbar degenerative spondylolisthesis.
AB  - Lumbar degenerative spondylolisthesis (DS) is a common cause of low back pain,
      radiculopathy, and/or neurogenic claudication. Treatment begins with a trial of
      nonsurgical methods, including physical therapy, NSAIDs, and epidural
      corticosteroid injections. Surgical treatment with decompression and fusion is
      recommended for patients who do not respond to this initial regimen. Although
      much has been published in the past two decades on the surgical management of DS,
      the optimal method remains controversial. Interbody fusion may improve
      arthrodesis rates and can be performed via numerous surgical approaches.
      Minimally invasive techniques continue to be developed. Particular attention to
      surgical management of DS in the elderly is warranted given the increasing
      numbers of elderly persons. Healthcare utilization in the future must take into
      account evidence-based medicine that establishes clinically effective practices
      while simultaneously being cost effective. 

PMID- 24668348
TI  - Human hepatocellular carcinoma-infiltrating CD4+CD69+Foxp3- regulatory T cell
      suppresses T cell response via membrane-bound TGF-beta1.
AB  - Tumors can recruit, induce, and expand regulatory T cells (Tregs) to suppress
      antitumor immune responses for survival and progression. The complicated tumor
      related Treg subsets and their functional mechanisms are not fully addressed yet.
      We have previously identified a novel CD4+CD69+Foxp3- Treg subset in tumor
      bearing mice, which suppresses CD4 T cell response via membrane-bound
      transforming growth factor beta 1 (mTGF-beta1) and then promotes tumor
      progression. In hepatocellular carcinoma patients, here, we identified tumor
      infiltrating human CD4+CD69+ Tregs which represent ~67.2 % of tumor-infiltrating
      CD4 T cells that is significantly higher than conventional CD4+CD25+Foxp3+ Tregs.
      They expressed mTGF-beta1, PD-1, and CTLA-4, but not CD25 or Foxp3, and only
      produced a little interleukin (IL)-10 and TGF-beta1. More importantly, they
      significantly suppressed CD4 T cell response via mTGF-beta1 in vitro.
      Furthermore, the percentage of these CD4+CD69+ Tregs in tumor tissue was
      significantly correlated with tumor progression, which is more pronounced at the
      late stage of cancer patients. Thus, we have identified a tumor-induced new
      population of human CD4+CD69+ Tregs in cancer patients with phenotype of CD25
      Foxp3-mTGF-beta1+CTLA-4+PD-1+, and these Tregs can suppress antitumor immune
      response via mTGF-beta1. Our results not only enrich the family of Treg subsets,
      providing new mechanistic insight to tumor-induced immune suppression in human,
      but also suggest a potential target for cancer immunotherapy. KEY MESSAGE:
      CD4+CD69+Foxp3- regulatory T cells were identified in hepatocellular carcinoma
      patients. These Treg cells inhibit T cell response via membrane-bound TGF-beta.
      The percentage of these cells was significantly correlated with tumor
      progression. The percentage of these cells was higher than conventional
      CD4+CD25+Foxp3+ Tregs. These Treg cells not only exist in tumor-bearing mice, but
      also in cancer patients.

PMID- 24668351
TI  - Pelvic resection: current concepts.
AB  - Pelvic resection is a technique that involves surgical resection of portions of
      the pelvic girdle. Historically, this procedure was known as internal
      hemipelvectomy. Hemipelvectomy is a resection that includes the ipsilateral limb.
      The main indication for these procedures is primary malignant tumors of the
      pelvis, but in rare cases they are indicated for metastatic lesions, infection,
      or trauma. Reconstruction is dictated by the extent of the resection and the
      remaining structures. Surgical technique is dictated by histology of the tumor
      and location of the lesion. A multidisciplinary team is required. The patient and
      family should undergo counseling preoperatively to discuss morbidity and
      mortality, the extensive rehabilitation process, and life expectancy. 

PMID- 24668352
TI  - Oncologic conditions that simulate common sports injuries.
AB  - Primary bone and soft-tissue tumors that mimic common sports injuries are
      relatively rare and are not often encountered by most orthopaedists. Prompt and
      accurate diagnosis of these tumors is crucial to maximize the clinical outcome.
      Many bone and soft-tissue tumors present disproportionately in young and active
      patients who are often involved in athletic activities. Thus, the clinician may
      misdiagnose these rare tumors as more common sports injuries. Symptoms that
      should raise suspicion for a neoplastic process include pain unrelated to
      activity and a clinical course that does not follow the typically expected
      recovery for a common sports injury. An awareness of the salient features of
      several bone and soft-tissue tumors as well as nononcologic processes that may
      simulate sports injuries can aid clinicians in the prompt diagnosis and clinical
      decision making of these rare tumors. 

PMID- 24668353
TI  - Metatarsophalangeal joint instability of the lesser toes and plantar plate
      deficiency.
AB  - Our understanding of lesser toe metatarsophalangeal joint instability has
      increased substantially over the past few decades. Some recent articles on the
      subject have provided detailed anatomic descriptions that help to characterize
      the primary stabilizing structures of the joint. Some surgeons now advocate the
      incorporation of a primary repair of the plantar plate into the surgical plan for
      correction of metatarsophalangeal joint deviation in the sagittal and transverse
      planes. New surgical techniques have been developed to expose, inspect, and
      reliably repair the plantar plate, if necessary. Dorsal and plantar approaches
      have both been used successfully to repair the plantar plate. Tears of the
      plantar plate can be repaired primarily or advanced on the base of the proximal
      phalanx through bone tunnels. Outcomes of these procedures are promising, with
      improvements in pain and function reported along with sustained deformity
      correction. 

PMID- 24668354
TI  - Congenital fibular deficiency.
AB  - Congenital fibular deficiency (CFD) is characterized by a wide spectrum of
      manifestations ranging from mild limb length inequality (LLI) to severe
      shortening, with foot and ankle deformities and associated anomalies. The
      etiology of CFD remains unclear. Treatment goals are to achieve normal weight
      bearing, a functional plantigrade foot, and equal limb length. The recent Birch
      classification system has been proposed to provide a treatment guide: the
      functionality of the foot, LLI, and associated anomalies should be taken into
      account for decision-making. Treatment options include orthosis or
      epiphysiodesis, Syme or Boyd amputation and prosthetic rehabilitation, limb
      lengthening procedures, and foot and ankle reconstruction. The outcome of
      amputation for severe forms of CFD has shown favorable results and fewer
      complications compared with those of limb lengthening. Nevertheless, advances in
      the limb lengthening techniques may change our approach to treating patients with
      CFD and might extend the indications for reconstructive procedures to the
      treatment of severe LLI and foot deformities. 

PMID- 24668355
TI  - Non-arthroplasty treatment of osteoarthritis of the knee.
AB  - The American Academy of Orthopaedic Surgeons has developed an Appropriate Use
      Criteria (AUC) on the Non-Arthroplasty Treatment of Osteoarthritis of the Knee
      (OAK). Evidence-based information, in conjunction with clinical expertise of
      physicians, was used to develop the criteria to improve patient care and obtain
      best outcomes while considering the subtleties and distinctions necessary in
      making clinical decisions. The OAK AUC clinical scenarios were derived from
      patient indications that generally accompany OAK as well as from the current
      evidence-based clinical practice guidelines and its supporting literature. The
      576 patient scenarios and 10 treatments were developed by the Writing Panel, a
      group of clinicians who are specialists in this AUC topic. Next, the Review
      Panel, a separate group of volunteer physicians, independently reviewed these
      materials to ensure that they were representative of patient scenarios clinicians
      are likely to encounter in daily practice. Finally, the multidisciplinary Voting
      Panel (made up of specialists and nonspecialists) rated the appropriateness of
      treatment of each patient scenario using a 9-point scale to designate a treatment
      as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to
      6), or Rarely Appropriate (median rating, 1 to 3). The final appropriateness
      ratings assigned by the voting panel can be accessed online via the AAOS OAK AUC
      web-based mobile application at: www.aaos.org/aucapp. 

PMID- 24668356
TI  - AAOS appropriate use criteria: optimizing the non-arthroplasty management of
      osteoarthritis of the knee.

PMID- 24668357
TI  - Musculoskeletal modeling for hip replacement outcome analyses and other
      applications.

PMID- 24668358
TI  - Core stability exercise is as effective as task-oriented motor training in
      improving motor proficiency in children with developmental coordination disorder:
      a randomized controlled pilot study.
AB  - OBJECTIVE: To compare the effectiveness of a core stability program with a task
      oriented motor training program in improving motor proficiency in children with
      developmental coordination disorder (DCD). DESIGN: Randomized controlled pilot
      trial. SETTING: Outpatient unit in a hospital. PARTICIPANTS: Twenty-two children
      diagnosed with DCD aged 6-9 years were randomly allocated to the core stability
      program or the task-oriented motor program. INTERVENTION: Both groups underwent
      their respective face-to-face training session once per week for eight
      consecutive weeks. They were also instructed to carry out home exercises on a
      daily basis during the intervention period. MAIN MEASURES: Short Form of the
      Bruininks-Oseretsky Test of Motor Proficiency (Second Edition) and Sensory
      Organization Test at pre- and post-intervention. RESULTS: Intention-to-treat
      analysis revealed no significant between-group difference in the change of motor
      proficiency standard score (P=0.717), and composite equilibrium score derived
      from the Sensory Organization Test (P=0.100). Further analysis showed significant
      improvement in motor proficiency in both the core stability (mean change
      (SD)=6.3(5.4); p=0.008) and task-oriented training groups (mean
      change(SD)=5.1(4.0); P=0.007). The composite equilibrium score was significantly
      increased in the task-oriented training group (mean change (SD)=6.0(5.5);
      P=0.009), but not in the core stability group (mean change(SD) =0.0(9.6);
      P=0.812). In the task-oriented training group, compliance with the home program
      was positively correlated with change in motor proficiency (rho=0.680, P=0.030)
      and composite equilibrium score (rho=0.638, P=0.047). CONCLUSION: The core
      stability exercise program is as effective as task-oriented training in improving
      motor proficiency among children with DCD.

PMID- 24668359
TI  - Clinical feasibility of the Nintendo WiiTM for balance training post-stroke: a
      phase II randomized controlled trial in an inpatient setting.
AB  - OBJECTIVE: To investigate the feasibility and potential efficacy of the Nintendo
      WiiTM for balance rehabilitation after stroke. DESIGN: Phase II, single-blind,
      randomized controlled trial. SETTING: Inpatient rehabilitation facility.
      SUBJECTS: Thirty adults (mean age 63.6 (14.7) years) undergoing inpatient
      rehabilitation who were less than three months post-stroke and able to stand
      unsupported. INTERVENTIONS: Participants were allocated to a Balance Group, using
      the 'Wii Fit Plus' in standing, or Upper Limb Group, using the 'Wii Sports/Sports
      Resort' in sitting. Both groups undertook three 45 minute sessions per week over
      two to four weeks in addition to standard care. MAIN MEASURES: The primary focus
      was feasibility, addressed by recruitment, retention, adherence, acceptability
      and safety. Efficacy was evaluated by balance, mobility and upper limb outcomes.
      RESULTS: Twenty-one percent of individuals screened were recruited and 86% (n =
      30) of eligible people agreed to participate. Study retention and session
      adherence was 90% and > 99%, respectively, at two weeks; dropping to 70% and 87%
      at four weeks due to early discharge. All participants reported enjoying the
      sessions and most felt they were beneficial. No major adverse events occurred.
      Wii use by the Balance Group was associated with trends for improved balance,
      with significantly greater improvement in outcomes including the Step Test and
      Wii Balance Board-derived centre of pressure scores. The Upper Limb Group had
      larger, non-significant changes in arm function. CONCLUSIONS: A Wii-based
      approach appears feasible and promising for post-stroke balance rehabilitation. A
      larger randomized controlled trial is recommended to further investigate
      efficacy.

PMID- 24668360
TI  - Body awareness therapy in persons with stroke: a pilot randomized controlled
      trial.
AB  - OBJECTIVE: To investigate the effects of body awareness therapy on balance,
      mobility, balance confidence, and subjective health status in persons with
      stroke. DESIGN: A pilot randomized controlled study with follow-up at one and 4-6
      weeks after the intervention period. SETTING: Four primary healthcare centres in
      Orebro County Council. SUBJECTS: Persons more than six months post stroke, with
      walking ability of 100 metres. INTERVENTION: The experimental intervention was
      body awareness therapy in groups once a week for eight weeks. The controls were
      instructed to continue their usual daily activities. MAIN MEASURES: Berg Balance
      Scale, Timed Up and Go Test, Timed Up and Go Test with a cognitive component, 6
      minute walk test, and Timed-Stands Test. Self-rated balance confidence was
      assessed using the Activities-specific Balance Confidence Scale, and subjective
      health status using the Short Form 36 (SF-36) questionnaire. RESULTS: A total of
      46 participants were included (mean age 64 years); 24 in the experimental
      intervention group and 22 in the control group. No significant differences in
      changed scores over time were found between the groups. Within the experimental
      intervention group, significant improvements over time was found for the tests
      Berg Balance Scale, Timed Up and Go cognitive, and 6-minute walk test. Within the
      control group, significant improvements over time were found for the Timed Up and
      Go Cognitive, and the Timed-Stands Test. CONCLUSION: In comparison to no
      intervention, no effects were seen on balance, mobility, balance confidence, and
      subjective health status after eight weeks of body awareness therapy.

PMID- 24668361
TI  - Does self-efficacy influence recovery and well-being in osteoarthritis patients
      undergoing joint replacement? A systematic review.
AB  - OBJECTIVE: To investigate the role of self-efficacy in functional recovery and
      well-being outcomes in osteoarthritis patients, undergoing hip or knee
      replacement surgery. DATA SOURCES: Studies were identified using MEDLINE via PUB
      med, PsycINFO and CINAHL from inception to July 2013. METHODS: Three search
      strategies that combined key terms of 'self-efficacy', 'functional recovery',
      'well-being' and 'joint replacement' were applied. Titles and abstracts were
      screened for eligibility and, accordingly, potentially eligible studies were
      retrieved for review. Included studies were assessed in terms of their quality,
      and data were extracted by two independent reviewers. A narrative synthesis of
      results was conducted. RESULTS: In total, 836 articles were identified and after
      electronic de-duplication, 708 articles remained. After screening 15 articles
      were retrieved as potentially eligible and eight articles were included in the
      review. Of the eight studies (n = 967 patients), seven had a prospective design
      and all studies were considered of good quality. No fully conclusive evidence for
      the influence of self-efficacy upon functional recovery outcomes was found. When
      the timing of self-efficacy measurement was examined, post-operative self
      efficacy was found to be related to functional recovery outcomes. CONCLUSION:
      Presurgical self-efficacy was the least consistent predictor of functional
      outcomes while postoperative self-efficacy was more consistently associated with
      recovery outcomes such as longer distance ambulation, exercise repetition and
      frequency, walking speed and disability.

PMID- 24668362
TI  - Ovarian reserve in women with primary antiphospholipid syndrome.
AB  - OBJECTIVE: The objective of this paper is to evaluate ovarian reserve in primary
      antiphospholipid syndrome (PAPS) women and the association between ovarian
      reserve tests and clinical and laboratorial parameters, and anti-corpus luteum
      antibody (anti-CoL). METHODS: We screened 85 female patients between 18 to 40
      years old with APS. Of these, 67 patients were excluded because of association
      with other autoimmune diseases (n = 42), contraindication or unwillingness to
      stop hormonal contraceptive (n = 21), current pregnancy or breastfeeding (n = 3)
      and previous ovarian surgery (n = 1). Therefore, a cross-sectional study was
      conducted in 18 PAPS patients and 24 healthy women. They were evaluated at early
      follicular phase with measurement of follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), estradiol, and anti-Mullerian hormone (AMH) and
      sonographic antral follicle count (AFC). Serum measurement of anti-CoL was
      determined by immunoblot analysis. All analyses were performed after at least six
      months from the last intake of hormonal contraceptive and resumption of
      menstruation. RESULTS: The mean age was comparable in PAPS and controls (33.0 +/-
      5.0 vs. 30.4 +/- 7.0 years; p = 0.19). Regarding ovarian reserve tests, the
      frequencies of low AFC (<=10) (56% vs. 22%, p = 0.04) and very low AFC (<=5) (37%
      vs. 9%, p = 0.04) were significantly higher in PAPS patients than controls.
      Trends of higher frequencies of reduced (<1.0 ng/ml), low (<0.5 ng/ml) and
      negligible (<0.2 ng/ml) AMH levels were found in PAPS patients (p = 0.08, p =
      0.07 and p = 0.07, respectively). FSH, LH and estradiol were similar in patients
      and controls. There was no association between low ovarian reserve and specific
      types of antiphospholipid antibodies. Anti-CoL was solely observed in PAPS
      patients (11% vs. 0%; p = 0.177) and was not related to ovarian reserve tests.
      CONCLUSION: Women suffering from PAPS possessed reduced ovarian reserve, with
      prevalence greater than 50%.

PMID- 24668363
TI  - A study of generation and rupture of soap films.
AB  - What are the lifetime and maximum length of a soap film pulled at a velocity V
      out of a bath of soapy solution? This is the question we explore in this article
      by performing systematic film rupture experiments. We show that the lifetime and
      maximal length of the films are fairly reproducible and controlled only by
      hydrodynamics. For surfactants with high surface elastic modulus, we argue that
      the rupture is triggered by the expansion of a thinning zone at the top of the
      film. The length ltz of this zone expands with time at a velocity equal to V/2,
      which can be obtained by a balance between gravity and viscous forces. The film
      lifetime is then found to decrease with the pulling velocity V, which implies
      that the surface tension gradient along the film increases with V. This surface
      tension gradient is found to be surprisingly small. Finally, the lifetime of
      films stabilised by solutions with small surface elastic modulus turns out to be
      much shorter than the ones for films with rigid interfaces. 

PMID- 24668365
TI  - Salmonella-mediated tumor regression involves targeting of tumor myeloid
      suppressor cells causing a shift to M1-like phenotype and reduction in
      suppressive capacity.
AB  - The effectiveness of attenuated Salmonella in inhibiting tumor growth has been
      demonstrated in many therapeutic models, but the precise mechanisms remain
      incompletely understood. In this study, we show that the anti-tumor capacity of
      Salmonella depends on a functional MyD88-TLR pathway and is independent of
      adaptive immune responses. Since myeloid suppressor cells play a critical role in
      tumor growth, we investigated the consequences of Salmonella treatment on myeloid
      cell recruitment, phenotypic characteristics, and functional activation in spleen
      and tumor tissue of B16.F1 melanoma-bearing mice. Salmonella treatment led to
      increased accumulation of splenic and intratumoral CD11b(+)Gr-1(+) myeloid cells,
      exhibiting significantly increased expression of various activation markers such
      as MHC class II, costimulatory molecules, and Sca-1/Ly6A proteins. Gene
      expression analysis showed that Salmonella treatment induced expression of iNOS,
      arginase-1 (ARG1), and IFN-gamma in the spleen, but down-regulated IL-4 and TGF
      beta. Within the tumor, expression of iNOS, IFN-gamma, and S100A9 was markedly
      increased, but ARG1, IL-4, TGF-beta, and VEGF were inhibited. Functionally,
      splenic CD11b(+) cells maintained their suppressive capacity following Salmonella
      treatment, but intratumoral myeloid cells had significantly reduced suppressive
      capacity. Our findings demonstrate that administration of attenuated Salmonella
      leads to phenotypic and functional maturation of intratumoral myeloid cells
      making them less suppressive and hence enhancing the host's anti-tumor immune
      response. Modalities that inhibit myeloid suppressor cells may be useful adjuncts
      in cancer immunotherapy. 

PMID- 24668364
TI  - Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer
      by effective inhibition of EGFR/ErbB2 heterodimerization and signaling.
AB  - The anti-ErbB2 antibody trastuzumab has currently been approved for ErbB2
      positive gastric cancer. Despite the effectiveness of trastuzumab, resistance is
      common. Thus, there is an urgent need to overcome trastuzumab resistance. Here,
      we obtain a trastuzumab-resistant cell line, which is derived from the human
      gastric cancer NCI-N87 cell line, by modeling the development of acquired
      resistance in patients. Our data show that combining trastuzumab and cetuximab
      leads to a significant decrease in EGFR/ErbB2 heterodimers and signaling compared
      with either antibody alone, and the combination results in greater antitumor
      activity against the trastuzumab-resistant NCI-N87 cell line, both in vitro and
      in vivo, suggesting that a combined EGFR/ErbB2 inhibition may overcome
      trastuzumab resistance. 

PMID- 24668368
TI  - Gastric obstruction due to intramural pseudocyst associated with heterotopic
      pancreas.
AB  - An unusual case of gastric outlet obstruction caused by a gastric intramural
      pseudocyst associated with heterotopic pancreas is illustrated. Heterotopic
      pancreas is defined as the presence of aberrant pancreatic tissue that is
      anatomically and vascularly distinct from the pancreas itself (Liu et al. Am
      Surg. 78:E141-3, 2012). Heterotopic pancreatic tissue has been reported in many
      locations along the gastrointestinal tract, identified most commonly in the
      stomach where it is usually an asymptomatic anatomic curiosity than a source of
      clinical concern. We encountered an unusual instance in which heterotopic
      pancreas in the distal stomach was associated with heterotopic pancreatitis and
      intramural pseudocyst formation that led to gastric obstruction. 

PMID- 24668366
TI  - Spatiotemporal profile and essential role of RBM3 expression after spinal cord
      injury in adult rats.
AB  - Hypoxia and other adverse conditions are usually encountered by rapidly growing
      cells. The RNA-binding motif protein 3 (RBM3) is induced by low temperature and
      hypoxia. However, its expression and function in spinal cord injury are still
      unclear. To investigate the certain expression and biological function in the
      central nervous system, we performed an acute spinal cord contusion injury (SCI)
      model in adult rats. Western blot analysis indicated a striking expression
      upregulation of RBM3 after spinal cord injury (SCI). Double immunofluorescence
      staining prompted that RBM3 immunoreactivity was found in astrocytes and neurons.
      Interestingly, RBM3 expression was increased predominantly in astrocytes.
      Furthermore, colocalization of RBM3 with proliferating cell nuclear antigen
      (PCNA) was detected in astrocytes. To further understand whether RBM3 plays a
      role in astrocyte proliferation, we applied lipopolysaccharide (LPS) to induce
      astrocyte proliferation in vitro. Western blot analysis demonstrated that RBM3
      expression was positively correlated with PCNA expression following LPS
      stimulation. Immunofluorescence analysis showed that the expression of RBM3 was
      also changed following the stimulation of astrocytes with LPS, which was parallel
      with the data in vivo. Additionally, knocking RBM3 down with small interfering
      RNA (siRNA) demonstrated that RBM3 might play a significant role in the
      proliferation of astrocytes treated by hypoxia in vitro. These results suggest
      that RBM3 may be involved in the proliferation of astrocytes after SCI. To
      summarize, we firstly uncover the temporal and spatial expression changes of RBM3
      in spinal cord injury. Our data suggest that RBM3 might be implicated in central
      nervous system pathophysiology after SCI. 

PMID- 24668367
TI  - Utility of the sendai consensus guidelines for branch-duct intraductal papillary
      mucinous neoplasms: a systematic review.
AB  - INTRODUCTION: The Sendai Consensus Guidelines (SCG) was formulated in 2006 to
      guide the management of intraductal papillary mucinous neoplasms (IPMN). The main
      area of controversy is the criteria for selection of branch duct (BD)-IPMN for
      resection. Although these guidelines have gained widespread acceptance, there is
      limited data to date supporting its use. This systematic review is performed to
      evaluate the utility of the Sendai Consensus Guidelines (SCG) for BD-IPMN.
      METHODS: Studies evaluating the clinical utility of the SCG in surgically
      resected neoplasms were identified. The SCG were retrospectively applied to all
      resected neoplasms in these studies. BD-IPMNs which met the criteria for
      resection were termed SCG+ve and those for surveillance were termed SCG-ve.
      RESULTS: Twelve studies were included, of which, 9 were suitable for pooled
      analysis. There were 690 surgically resected BD-IPMNs, of which, 24% were
      malignant. Five hundred one BD-IPMNs were classified as SCG+ve and 189 were SCG
      ve. The positive predictive value (PPV) of SCG+ve neoplasms ranged from 11 to 52%
      and the NPV of SCG-ve neoplasms ranged from 90 to 100%. Overall, there were
      150/501 (29.9%) of malignant BD-IPMNs in the SCG+ve group and 171/189 (90%) of
      benign BD-IPMNs in the SCG-ve group. Of the 18 reported malignant (11 invasive)
      BD-IPMNs in the SCG-ve group, 17 (including all 11 invasive) were from a single
      study. When the results from this single study were excluded, 170/171 (99%) of
      SCG-ve BD-IPMNs were benign. CONCLUSION: The results of this review confirm the
      limitations of the SCG for BD-IPMN. The PPV of the SCG in predicting a malignant
      BD-IPMN was low and some malignant lesions may be missed based on these
      guidelines.

PMID- 24668369
TI  - Teaching psychiatry residents about culture-bound syndromes: implementation of a
      modified team-based learning program.

PMID- 24668370
TI  - Attitudes of medical students toward psychiatry in a Chilean medical school.
AB  - OBJECTIVE: The authors assess the attitudes of seventh-year medical students with
      regard to psychiatry and patients with psychiatric illness during the psychiatry
      clerkship. METHODS: A 32-item questionnaire regarding attitudes toward psychiatry
      and patients with psychiatric illness was administered at the beginning of the
      psychiatry clerkship. RESULTS: One hundred and ten seventh-year students
      participated in the study, providing responses anonymously. Average negative
      attitude item score was 2.45 +/- 0.3 (range 1.7-3.3). Eighty-three students (75
      %) responded to all the questions with an average negative attitude item score of
      2.43 +/- 0.3 (range 1.7-3.3) and a total negative attitude item score of 77.9 +/-
      10.3 (range 55-104). CONCLUSIONS: Undergraduate students of a Chilean medical
      school showed fairly positive attitudes toward psychiatry and toward patients
      with psychiatric illness.

PMID- 24668371
TI  - Curating Psychiatric Services.

PMID- 24668372
TI  - Competitive match-play tennis under heat stress: a challenge for all players.

PMID- 24668373
TI  - Hydration and thermal strain during tennis in the heat.
AB  - Competitive tennis in the heat can prompt substantial sweat losses and extensive
      consequent body water and electrolyte deficits, as well as a level of thermal
      strain that considerably challenges a player's physiology, perception of effort,
      and on-court well-being and performance. Adequate hydration and optimal
      performance can be notably difficult to maintain when multiple same-day matches
      are played on successive days in hot weather. Despite the recognised effects of
      the heat, much more research needs to be carried out to better appreciate the
      broader scope and full extent of the physiological demands and hydration and
      thermal strain challenges facing junior and adult players in various
      environments, venues and competition scenarios. However, certain recommendations
      of best practices should be emphasised to minimise exertional heat illness risk
      and improve player safety, well-being and on-court performance. 

PMID- 24668374
TI  - Recovery interventions and strategies for improved tennis performance.
AB  - Improving the recovery capabilities of the tennis athlete is receiving more
      emphasis in the research communities, and also by practitioners (coaches,
      physical trainers, tennis performance specialists, physical therapists, etc). The
      purpose of this article was to review areas of recovery to limit the severity of
      fatigue and/or speed recovery from fatigue. This review will cover four broad
      recovery techniques commonly used in tennis with the belief that the
      interventions may improve athlete recovery and therefore improve adaptation and
      future performance. The four areas covered are: (1) temperature-based
      interventions, (2) compressive clothing, (3) electronic interventions and (4)
      nutritional interventions. 

PMID- 24668376
TI  - The evolution and impact of science in tennis: eight advances for performance and
      health.

PMID- 24668375
TI  - Fitness testing of tennis players: how valuable is it?
AB  - In tennis, sport-specific technical skills are predominant factors, although a
      complex profile of physical performance factors is also required. The fitness
      test batteries assist in examining tennis players' capabilities for performance
      at different levels in the laboratory as well as in the field, in the junior or
      elite level. While laboratory tests can be, and are, used to evaluate basic
      performance characteristics of athletes in most individual sports, in a more
      specific approach, field-based methods are better suited to the demands of
      complex intermittent sports like tennis. A regular test battery performed at
      different periods of the year allows to obtain an individual's performance
      profile, as well as the ability to prescribe individual training interventions.
      Thus, the aim of the present review was to describe and evaluate the different
      physical tests recommended and used by practitioners, sports scientists and
      institutions (national tennis federations). 

PMID- 24668377
TI  - Thermal, physiological and perceptual strain mediate alterations in match-play
      tennis under heat stress.
AB  - OBJECTIVES: This study compared the thermal, physiological and perceptual
      responses associated with match-play tennis in HOT (~34 degrees C wet-bulb-globe
      temperature (WBGT)) and COOL (~19 degrees C WBGT) conditions, along with the
      accompanying alterations in match characteristics. METHODS: 12 male tennis
      players undertook two matches for an effective playing time (ie, ball in play) of
      20 min, corresponding to ~119 and ~102 min of play in HOT and COOL conditions,
      respectively. Rectal and skin temperatures, heart rate, subjective ratings of
      thermal comfort, thermal sensation and perceived exertion were recorded, along
      with match characteristics. RESULTS: End-match rectal temperature increased to a
      greater extent in the HOT (~39.4 degrees C) compared with the COOL (~38.7 degrees
      C) condition (p<0.05). Thigh skin temperature was higher throughout the HOT match
      (p<0.001). Heart rate, thermal comfort, thermal sensation and perceived exertion
      were also higher during the HOT match (p<0.001). Total playing time was longer in
      the HOT compared with the COOL match (p<0.05). Point duration (~7.1 s) was
      similar between conditions, while the time between points was ~10 s longer in the
      HOT relative to the COOL match (p<0.05). This led to a ~3.4% lower effective
      playing percentage in the heat (p<0.05). Although several thermal, physiological
      and perceptual variables were individually correlated to the adjustments in time
      between points and effective playing percentage, thermal sensation was the only
      predictor variable associated with both adjustments (p<0.005). CONCLUSIONS: These
      adjustments in match-play tennis characteristics under severe heat stress appear
      to represent a behavioural strategy adopted to minimise or offset the sensation
      of environmental conditions being rated as difficult.

PMID- 24668378
TI  - Heat stress does not exacerbate tennis-induced alterations in physical
      performance.
AB  - OBJECTIVES: To assess the time course of changes in physical performance in
      response to match-play tennis under heat stress. METHODS: Two matches consisting
      of 20 min of effective playing time (2*10 min segments) were played in COOL (~102
      min; ~22 degrees C and 70% relative humidity (RH)) and HOT (~119 min; ~36 degrees
      C and 35% RH) environments. Repeated-sprint ability (3*15 m, 15 s rest), 15 m
      sprint time with a direction change (180 degrees ), vertical jump height (squat
      and countermovement jumps) and leg stiffness (multirebound jumps) were assessed
      in 12 competitive male players prematch, midmatch and postmatch, and 24 and 48 h
      after match completion. RESULTS: During the repeated-sprint ability test, initial
      (+2.3% and +3.1%) and cumulated sprint (+1.5% and +2.8%) times increased from
      prematch to midmatch and postmatch, respectively (p<0.001), while the sprint
      decrement score did not change. Match-play tennis induced a slowing (average of
      both conditions: +1.1% and +1.3% at midmatch and postmatch time points; p=0.05)
      of 15 m sprint time with direction change. Compared with prematch, leg stiffness
      (-6.4% and -6.5%; p<0.001) and squat jump height (-1.5% and -2.4%; p=0.05), but
      not countermovement jump height (-0.7% and -1.3%; p>0.05), decreased midmatch and
      postmatch, respectively, regardless of the condition. Complete recovery in all
      physical performance markers occurred within 24 h. CONCLUSIONS: In tennis, match
      related fatigue is characterised by impaired repeated-sprint ability, explosive
      power and leg stiffness at midmatch and postmatch, with values restored to
      prematch baseline 24 h into recovery. In addition, physical performance responses
      (match and recovery kinetics) are identical when competing in cool and hot
      environments.

PMID- 24668379
TI  - Neuromuscular adjustments of the knee extensors and plantar flexors following
      match-play tennis in the heat.
AB  - OBJECTIVES: This study tested the hypothesis that impairments in lower limb
      maximal strength and voluntary activation (VA) are exacerbated following match
      play tennis in hot compared with cool conditions. METHODS: Torque and VA were
      evaluated during brief (5 s) and sustained (20 s) maximal voluntary isometric
      contractions of the knee extensors (KE) and plantar flexors (PF) in 12 male
      tennis players before (pre) and after (post, 24 h and 48 h) ~115 min of play in
      hot (~37 degrees C) and cool (~22 degrees C) conditions. RESULTS: Rectal
      temperature was higher following play in hot than in cool (~39.2 vs ~38.5 degrees
      C; p<0.05). Torque production decreased from prematch to postmatch during the
      brief and sustained contractions in hot (KE: ~22%; PF: ~13%) and cool (KE: ~9%,
      PF: ~7%) (p<0.05). KE strength losses in hot were greater than in cool (p<0.05)
      and persisted for 24 h (p<0.05). Postmatch brief and sustained KE VA was lower in
      hot than in cool (p<0.05), in which VA was maintained. PF VA was maintained
      throughout the protocol. Peak twitch torque and maximum rates of torque
      development and relaxation in the KE and PF were equally reduced postmatch
      relative to prematch in hot and cool conditions (p<0.05), and were restored near
      baseline within 24 h. CONCLUSIONS: Neuromuscular system integrity of the lower
      limbs is compromised immediately following match-play tennis in hot and cool
      conditions due to the development of peripheral fatigue. The larger and
      persistent KE strength losses observed under heat stress are associated with
      greater levels of central fatigue especially during sustained contractions.

PMID- 24668380
TI  - Heat research guides current practices in professional tennis.

PMID- 24668381
TI  - Tennis in hot and cool conditions decreases the rapid muscle torque production
      capacity of the knee extensors but not of the plantar flexors.
AB  - OBJECTIVES: To assess the time course of changes in rapid muscle force/torque
      production capacity and neuromuscular activity of lower limb muscles in response
      to prolonged (~2 h) match-play tennis under heat stress. METHODS: The rates of
      torque development (RTD) and electromyographic activity (EMG; ie, root mean
      square) rise were recorded from 0 to 30, -50, -100 and -200 ms during brief (3-5
      s) explosive maximal isometric voluntary contractions (MVC) of the knee extensors
      (KE) and plantar flexors (PF), along with the peak RTD within the entirety of the
      torque-time curve. These values were recorded in 12 male tennis players before
      (prematch) and after (postmatch, 24 and 48 h) match-play in HOT (~37 degrees C)
      and COOL (~22 degrees C) conditions. RESULTS: The postmatch core temperature was
      greater in the HOT (~39.4 degrees C) vs COOL (~38.7 degrees C) condition
      (p<0.05). Reductions in KE RTD occurred within the 0-200 ms epoch after
      contraction onset postmatch and at 24 h, compared with prematch, independent of
      environmental conditions (p<0.05). A similar reduction in the KE peak RTD was
      also observed postmatch relative to prematch (p<0.05). No differences in KE RTD
      values were observed after normalisation to MVC torque. Furthermore, the rate of
      KE EMG activity rise remained unchanged. Conversely, the PF contractile RTD and
      rate of EMG activity rise were unaffected by the exercise or environmental
      conditions. CONCLUSIONS: In the KE, a reduction in maximal torque production
      capacity following prolonged match-play tennis appears to account for the
      decrease in the rate of torque development, independent of environmental
      conditions, while remaining unchanged in the PF.

PMID- 24668382
TI  - The impact of match-play tennis in a hot environment on indirect markers of
      oxidative stress and antioxidant status.
AB  - OBJECTIVES: The purpose of this study was to determine the impact of changes in
      oxidative stress and antioxidant status in response to playing tennis in HOT (~36
      degrees C and 35% relative humidity (RH)) and COOL (~22 degrees C and 70% RH)
      conditions. METHODS: 10 male tennis players undertook two matches for an
      effective playing time (ie, ball in play) of 20 min, corresponding to ~122 and
      ~107 min of total play in HOT and COOL conditions, respectively. Core body
      temperature, body mass and indirect markers of oxidative stress (diacrons
      reactive oxygen metabolic test) and antioxidant status (biological antioxidant
      potential test) were assessed immediately prematch, midmatch and postmatch, and
      24 and 48 h into recovery. RESULTS: Regardless of the condition, oxidative stress
      remained similar throughout play and into recovery. Likewise, match-play tennis
      in the COOL had no impact on antioxidant status. However, antioxidants status
      increased significantly in the HOT compared with COOL environment (p<0.05). Body
      mass losses (~0.5 kg) were similar between conditions. Rectal temperature
      increased during both matches (p<0.05), but with a greater magnitude in the HOT
      (39.3+/-0.5 degrees C) versus COOL (38.7+/-0.2 degrees C) environment (p<0.05).
      CONCLUSIONS: Match-play tennis in the heat does not exacerbate the development of
      oxidative stress, but significantly increases antioxidant status. These data
      suggest that the heat stress observed in the HOT environment may provide a
      necessary signal for the upregulation of antioxidant defence, dampening cellular
      damage.

PMID- 24668383
TI  - Coping with heat stress during match-play tennis: does an individualised
      hydration regimen enhance performance and recovery?
AB  - OBJECTIVES: To determine whether an individualised hydration regimen reduces
      thermal, physiological and perceptual strain during match-play tennis in the
      heat, and minimises alterations in neuromuscular function and physical
      performance postmatch and into recovery. METHODS: 10 men undertook two matches
      for an effective playing time (ball in play) of 20 min (~113 min) in ~37 degrees
      C and ~33% RH conditions. Participants consumed fluids ad libitum during the
      first match (HOT) and followed a hydration regimen (HYD) in the second match
      based on undertaking play euhydrated, standardising sodium intake and minimising
      body mass losses. RESULTS: HYD improved prematch urine specific gravity (1.013+/
      0.006 vs 1.021+/-0.009 g/mL; p<0.05). Body mass losses (~0.3%), fluid intake (~2
      L/h) and sweat rates (~1.6 L/h) were similar between conditions. Core temperature
      was higher during the first 10 min of effective play in HOT (p<0.05), but
      increased similarly (~39.3 degrees C) on match completion. Heart rate was higher
      (~11 bpm) throughout HOT (p<0.001). Thermal sensation was higher during the first
      7.5 min of effective play in HOT (p<0.05). Postmatch knee extensor and plantar
      flexor strength losses, along with reductions in 15 m sprint time and repeated
      sprint ability (p<0.05), were similar in both conditions, and were restored
      within 24 h. CONCLUSIONS: Both the hydration regimen and ad libitum fluid
      consumption allowed for minimal body mass losses (<1%). However, undertaking
      match-play in a euhydrated state attenuated thermal, physiological and perceptual
      strain. Maximal voluntary strength in the lower limbs and repeated-sprint ability
      deteriorated similarly in both conditions, but were restored within 24 h.

PMID- 24668385
TI  - Dynamics of the O(3P) + CH4 hydrogen abstraction reaction at hyperthermal
      collision energies.
AB  - Motivated by recent experiments on the title reaction at the high collision
      energy of 64 kcal mol(-1) reported by Minton et al., a detailed dynamics study
      was carried out using quasi-classical trajectory (QCT) calculations based on an
      analytical potential energy surface recently developed by our group, PES-2014.
      Our results reproduce the experimental evidence: most of the available energy
      appears as translational energy (80 +/- 10%) and scattering distribution is
      forward, suggesting a stripping mechanism associated with high impact parameters.
      Of special interest is the triple (angle-velocity) differential cross section (a
      combination of translational and scattering distributions), which shows the same
      structure associated with the products. Agreement with experiment lends
      confidence to the new PES-2014 surface; this is encouraging, furthermore, because
      its fitting was made with thermal behaviour in mind, and higher energy areas were
      neither sampled nor weighted sufficiently. 

PMID- 24668384
TI  - The development of fatigue during match-play tennis.
AB  - Data describing the activity profile and physiological characteristics of tennis
      match-play are extensive. However, these data have generally provided descriptive
      accounts of the one-off match-play of amateur or lowly ranked professional
      players lasting <3 h. Accordingly, these research efforts have likely failed to
      fully capture the demands of Grand Slam tennis match-play, particularly in the
      men's game where matches can last >5 h. Furthermore, there is a distinct lack of
      evidence-based insight regarding the manifestation of fatigue within and between
      tennis matches, notwithstanding that skeletal muscle function has been reported
      to reduce following prolonged match-play. Moreover, it is evident that match-play
      evokes pronounced and prolonged physiological, neuromuscular and psychological
      perturbations that may be exacerbated with consecutive days of match-play.
      Separate to these internal load responses, a collection of non-uniform movement
      and technical performance changes are reported, though rarely from match-play
      data. Consequently, direct or causal links between altered physiological or
      muscle contractile function and subsequent match-play outcomes are lacking.
      Indeed, emerging evidence seems to infer that players adjust their game strategy,
      and the resultant execution of stroke play, to accommodate any such deterioration
      in physiological function. The purpose of this review was to discuss the
      available literature in terms of the physiological, mechanical and psychological
      responses that occur during prolonged match-play in the context of their likely
      effect on match-play performance. 

PMID- 24668386
TI  - An analysis of the outcomes for patients with failed primary vitrectomy for
      rhegmatogenous retinal detachment.
AB  - PURPOSE: Our aim was to identify the timing of retinal redetachments and the
      prognosis for affected patients. METHODS: Retrospective review of electronic
      patient records and casenotes from two centres. Inclusion criteria were failed
      primary vitrectomy for rhegmatogenous retinal detachment during a 12-year period.
      Failure was defined as re- or persistent detachment of the retina prior to a
      further procedure or at final follow-up. RESULTS: The records of 133 cases of
      failed primary PPV for RRD were analysed. The mean age at time of primary surgery
      was 62.9 years, and mean follow-up was over 3 years from the date of primary
      surgery. In 72.9 % of cases, the redetachment was diagnosed within 2 months of
      the primary surgery. Eighty-five percent were diagnosed within 3 months, 89.5 %
      within 4 months, and 97.7 % within 6 months. For patients in whom the primary
      surgery had failed, the rates of attached retina at final follow-up were 80.5 %,
      or 68.8 % if PVR B/C were present at the time of primary surgery. The final
      follow-up success rates (attached retina with no tamponade) were 66.2 % for all
      patients, and 59.4 % for the subset with PVR B/C at the time of primary surgery
      respectively. Of the total, 33.8 % had one further vitreoretinal procedure, 30.8
      % two more, 25.6 % three more, and 5.3 % had four or more. Visual outcome was
      better with final success (attached retina and no tamponade, p < 0.0001) and
      worse with PVR B/C evident on diagnosis of failed primary surgery (p < 0.0001).
      CONCLUSIONS: A short duration of follow-up can over-estimate surgeon success
      rates for retinal detachment repair. For patients in whom primary surgery has
      failed, the prognosis for ultimate success is markedly lower than for primary
      surgery, and most patients require two or more further procedures to achieve
      this.

PMID- 24668387
TI  - Trabeculotomy ab interno with internal limiting membrane forceps for open-angle
      glaucoma.
AB  - PURPOSE: To describe a new technique to perform trabeculotomy ab interno on eyes
      with open-angle glaucoma (OAG). METHODS: This was a retrospective study. We
      inserted a 25-gauge forceps that is usually used for internal limiting membrane
      peeling into the anterior chamber, and grasped and pulled the inner wall of
      Schlemm's canal away from the canal. The inner wall of Schlemm's canal was
      stripped for about 100 degrees  to 120 degrees  in 26 eyes of 23 patients. The
      intraocular pressure (IOP) and number of glaucoma medications were recorded
      before, and 1 day, 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 19, 24, 27, 30,
      and 33 months after the surgery. The intra- and postoperative complications were
      recorded. RESULTS: The mean +/- standard deviation of the preoperative IOP was
      20.0 +/- 6.8 mmHg with a range from 10 to 38 mmHg (n = 26). The IOP was
      significantly reduced (P < 0.05; paired t-tests) at 1 week, 2 weeks, and 1, 3, 6,
      10, 12, 15, 17, 24, 19, 27, 30, and 33 months after the surgery. The mean
      preoperative number of glaucoma medications was significantly reduced (P < 0.001;
      paired t-tests) at 1 week, 2 weeks, and 1, 3, 6, 10, 12, 15, 17, 19, 24, 27, 30,
      and 33 months after the surgery. No vision-threatening complications were found
      in any of the cases, but there were blood clots in the anterior chamber
      postoperatively in 92.3 % of the cases. CONCLUSIONS: Trabeculotomy ab interno for
      OAG is effective but with some minor complications. A larger number of patients
      with longer follow-up periods are needed to determine the long-term effectiveness
      of this procedure.

PMID- 24668389
TI  - A multiscale approach to determine binding energy distribution on a strained
      surface.
AB  - A multiscale approach was developed by combining ab initio calculations with
      classical molecular mechanics (MM) simulations to investigate the adsorption and
      diffusion of an adatom on a strained and/or defective surface. Specifically, the
      binding energy of the adatom was calculated as a function of the local substrate
      strain near the adsorption site by an ab initio method and the strain
      distribution of a large defective surface was calculated by the MM method. Then a
      map of the binding energy of the adatom on a large defective surface was derived
      by bridging the DFT calculated binding energy and the MM determined strain
      distribution. As an example, the approach is applied to explore the adsorption
      and diffusion of a carbon atom on the Ni(111) surfaces with dislocations and
      grain boundaries, respectively. This approach bridges models of different length
      scales and can be extended to systems with an uneven distribution of strain or
      curvature. 

PMID- 24668388
TI  - Population-based comparison of biomarker concentrations for chemicals of concern
      among Latino-American and non-Hispanic white children.
AB  - Differences in cultural and economic status may place ethnic subgroups of
      children at higher risk for exposure, leading to heightened health risks, and
      health inequities. Although Latino-Americans represent 22% of all children in the
      United States, few studies have explored within-group differences in their
      exposure to toxicants. Using socio-demographic and biomarker data from the
      National Health and Nutrition Examination Survey from 1999 to 2008, we
      characterized determinants of health and estimated geometric means of
      environmental contaminant biomarkers (blood concentrations of lead and mercury,
      serum concentrations of dichlorodiphenyldichloroethylene [p,p'-DDE] and cotinine,
      and urinary metabolites of organophosphate [OP] pesticides and polycyclic
      aromatic hydrocarbons [PAHs]) among 4,257 Mexican American (MA), 677 Other Latino
      American (OL), and 3,370 Non-Hispanic White (NHW) children. MAs had the lowest
      levels of health insurance coverage and regular access to health care, and
      largest household size compared to NHWs and OLs. MAs had higher levels of p,p'
      DDE, lead, and cadmium while OLs had higher estimates of mercury relative to
      other groups. MAs had higher urinary metabolite concentrations of 2
      hydroxynaphthalene; otherwise MAs and OLs had lower concentrations of PAHs. NHWs
      had higher levels of cotinine and dimethylthiophosphate. For other OP
      metabolites, differences among groups were less clear. Lead and p,p'-DDE exposure
      differences likely reflect later and less regulatory control of these chemicals
      in Latin America. Additionally, poor quality housing with lead paint is more
      common in economically disadvantaged subpopulations. Dietary habits are possible
      sources of differential cadmium, mercury, and organophosphate exposure. Cotinine
      exposure differences by income and U.S.- vs. foreign-born may represent increased
      acculturation. These results, coupled with additional research on exposure
      sources may contribute to refinement of environmental health promotion programs
      for the fast-growing Latino-American population.

PMID- 24668390
TI  - Homeostasis of metals in the progression of Alzheimer's disease.
AB  - In order to study the involvement of metals in the progression of Alzheimer's
      disease, serum samples from patients with Alzheimer and mild cognitive impairment
      were investigated. For this purpose, metal content was analyzed after size
      fractionation of species and then, inter-element and inter-fraction ratios were
      computed. In this way, the analysis allowed discovering changes that could be
      used as markers of disease, but also provided a new insight into the interactions
      in the homeostasis of elements in neurodegeneration and its progression. Aluminum
      and labile forms of iron and copper were increased in demented patients, while
      manganese, zinc and selenium were reduced. Interestingly, levels of different
      elements, principally iron, aluminum and manganese, were closely inter-related,
      which could evidence a complex interdependency between the homeostasis of the
      different metals in this disorder. On the other hand, imbalances in metabolism of
      copper, zinc and selenium could be associated to abnormal redox status.
      Therefore, this study may contribute to our understanding of the pathological
      mechanisms related to metals in Alzheimer's disease. 

PMID- 24668392
TI  - Copper(II) complexes supported by click generated mixed NN, NO, and NS 1,2,3
      triazole based ligands and their catalytic activity in azide-alkyne
      cycloaddition.
AB  - The preparation and characterization of four new copper(ii) complexes supported
      by click generated mixed NN, NO, and NS 1,2,3-triazoles are reported. The four
      complexes display a 1 : 2 copper/ligand ratio and give monomeric units in the
      solid state. Crystal structures demonstrate that depending on the flexibility of
      the ligand NX (X = O, N, S) pendant arm, the coordination environment around the
      metal center can feature square planar or octahedral geometries. All four
      complexes are catalytically active at room temperature in a copper-catalyzed
      alkyne-azide cycloaddition (CuAAC) reaction using sodium ascorbate as a reducing
      agent and water-ethanol as a solvent mixture. Complex 8 supported by the NS
      ligand displayed the best catalytic performance of the series allowing for the
      easy and high yielding preparation of a variety of mono-, bis- and tris-1,2,3
      triazoles under low catalyst loadings. 

PMID- 24668391
TI  - Neoadjuvant chemotherapy with S-1 and cisplatin followed by D2 gastrectomy with
      para-aortic lymph node dissection for gastric cancer with extensive lymph node
      metastasis.
AB  - BACKGROUND: Locally advanced gastric cancer with extensive regional and/or para
      aortic lymph node (PAN) metastases is typically unresectable and associated with
      poor outcomes. This study investigated the safety and efficacy of S-1 plus
      cisplatin followed by extended surgery with PAN dissection for gastric cancer
      with extensive lymph node metastasis. METHODS: Patients with gastric cancer with
      bulky lymph node metastasis along the coeliac artery and its branches and/or PAN
      metastasis received two or three 28-day cycles of S-1 plus cisplatin, followed by
      gastrectomy with D2 plus PAN dissection. The primary endpoint was the percentage
      of complete resections with clear margins in the primary tumour (R0 resection). A
      target sample size of 50 with one-sided alpha of 0.105 and beta of approximately
      0.2 corresponded to an expected R0 rate of 65 per cent and a threshold of 50 per
      cent. RESULTS: Between February 2005 and June 2007, 53 patients were enrolled, of
      whom 51 were eligible. The R0 resection rate was 82 per cent. Clinical and
      pathological response rates were 65 and 51 per cent respectively. The 3- and 5
      year overall survival rates were 59 and 53 per cent respectively. During
      chemotherapy, grade 3/4 neutropenia occurred in 19 per cent and grade 3/4 non
      haematological adverse events in 15.4 per cent. The incidence of grade 3/4
      adverse events related to surgery was 12 per cent. There were no reoperations or
      treatment-related deaths. CONCLUSION: For locally advanced gastric cancer with
      extensive lymph node metastasis, 4-weekly S-1 plus cisplatin followed by surgery
      including PAN dissection was safe and effective for some patients. Further
      investigation of this treatment strategy is warranted.

PMID- 24668393
TI  - NMR methodologies in the analysis of blueberries.
AB  - An NMR analytical protocol based on complementary high and low field measurements
      is proposed for blueberry characterization. Untargeted NMR metabolite profiling
      of blueberries aqueous and organic extracts as well as targeted NMR analysis
      focused on anthocyanins and other phenols are reported. Bligh-Dyer and microwave
      assisted extractions were carried out and compared showing a better recovery of
      lipidic fraction in the case of microwave procedure. Water-soluble metabolites
      belonging to different classes such as sugars, amino acids, organic acids, and
      phenolic compounds, as well as metabolites soluble in organic solvent such as
      triglycerides, sterols, and fatty acids, were identified. Five anthocyanins
      (malvidin-3-glucoside, malvidin-3-galactoside, delphinidin-3-glucoside,
      delphinidin-3-galactoside, and petunidin-3-glucoside) and 3-O-alpha-l
      rhamnopyranosyl quercetin were identified in solid phase extract. The water
      status of fresh and withered blueberries was monitored by portable NMR and fast
      field cycling NMR. (1) H depth profiles, T2 transverse relaxation times and
      dispersion profiles were found to be sensitive to the withering. 

PMID- 24668394
TI  - Silicone ear plugs: are they safe for use?

PMID- 24668395
TI  - Kidney stone, flank pain and fever: a lethal clinical pitfall trap.

PMID- 24668396
TI  - Classifying emergency 30-day readmissions in England using routine hospital data
      2004-2010: what is the scope for reduction?
AB  - BACKGROUND: Many health systems across the globe have introduced arrangements to
      deny payment for patients readmitted to hospital as an emergency. The purpose of
      this study was to develop an exploratory categorisation based on likely causes of
      readmission, and then to assess the prevalence of these different types. METHODS:
      Retrospective analysis of 82 million routinely collected National Health Service
      hospital records in England (2004-2010) was undertaken using anonymised linkage
      of records at person-level. Numbers of 30-day readmissions were calculated.
      Exploratory categorisation of readmissions was applied using simple rules
      relating to International Classification of Diseases (ICD) diagnostic codes for
      both admission and readmission. RESULTS: There were 5 804 472 emergency 30-day
      readmissions over a 6-year period, equivalent to 7.0% of hospital discharges.
      Readmissions were grouped into hierarchically exclusive categories: potentially
      preventable readmission (1 739 519 (30.0% of readmissions)); anticipated but
      unpredictable readmission (patients with chronic disease or likely to need long
      term care; 1 141 987 (19.7%)); preference-related readmission (53 718 (0.9%));
      artefact of data collection (16 062 (0.3%)); readmission as a result of accident,
      coincidence or related to a different body system (1 101 818 (19.0%)); broadly
      related readmission (readmission related to the same body system (1 751 368
      (30.2%)). CONCLUSIONS: In this exploratory categorisation, a large minority of
      emergency readmissions (eg, those that are potentially preventable or due to data
      artefacts) fell into groups potentially amenable to immediate reduction. For
      other categories, a hospital's ability to reduce emergency readmission is less
      clear. Reduction strategies and payment incentives must be carefully tailored to
      achieve stated aims.

PMID- 24668397
TI  - A pain in the neck.

PMID- 24668398
TI  - An evaluation of the use of a two-tiered trauma team activation system in a UK
      major trauma centre.
AB  - OBJECTIVES AND BACKGROUND: Appropriate activation of multidisciplinary trauma
      teams improves outcome for severely injured patients but can disrupt normal
      service in the rest of the hospital. Derriford Hospital uses a two-tiered trauma
      team activation system. The emergency department trauma team (EDTT) is activated
      in response to a significant traumatic mechanism; the hospital trauma team (HTT)
      is activated when this mechanism coexists with physiological abnormality or
      specific anatomical injury. The aim of this study was to compare characteristics,
      process measures and outcomes between patients treated by EDTTs or HTTs to
      evaluate the approach in a UK setting. METHODS: A retrospective database review
      was performed using Trauma Audit Research Network (TARN) and the local source
      trauma database. Patients who activated a trauma team between 1 April and 30
      September 2012 were included. Patients were categorised according to the type of
      trauma team activated. Data included time to X-rays, time to CT, time to
      intubation, numbers discharged from ED, intensive care unit admission, injury
      severity score and mortality. RESULTS: During the study period, 456 patients
      activated a trauma team with 358 EDTT and 98 HTT activations. Patients seen by
      the ED team were significantly less likely to have severe injury or require
      hospital admission, intubation, emergency operation or blood transfusion.
      Differences in time taken to key investigations were statistically but not
      clinically significant. CONCLUSIONS: A two-tiered trauma team activation system
      is an efficient and cost-effective way of dealing with trauma patients presenting
      to a major trauma centre in the UK.

PMID- 24668399
TI  - [Delirium in patients with neurological diseases: diagnosis, management and
      prognosis].
AB  - Delirium is a common acute neuropsychiatric syndrome. It is characterized by
      concurrent disturbances of consciousness and attention, perception, reasoning,
      memory, emotionality, the sleep-wake cycle as well as psychomotor symptoms.
      Delirium caused by alcohol or medication withdrawal is not the subject of the
      current review. Specific predisposing and precipitating factors have been
      identified in delirium which converge in a common final pathway of global brain
      dysfunction. The major predisposing factors are older age, cognitive impairment
      or dementia, sensory deficits, multimorbidity and polypharmacy. Delirium is
      always caused by one or more underlying pathologies which need to be identified.
      In neurology both primary triggers of delirium, such as stroke or epileptic
      seizures and also secondary triggers, such as metabolic factors or medication
      side effects play a major role. Nonpharmacological interventions are important in
      the prevention of delirium and lead to an improvement in prognosis. Delirium is
      associated with increased mortality and in the long term the development of
      cognitive deficits and functional impairment. 

PMID- 24668400
TI  - [Fumaric acid as therapeutic agent for multiple sclerosis].
AB  - After the approval of fumaric acid in February 2014 another first line agent is
      now available for the treatment of multiple sclerosis (MS). Along with the
      various beta interferon preparations, glatiramer acetate, teriflunomide and
      fumaric acid add to the repertoire of oral therapeutics for the initial treatment
      of relapsing remitting MS in daily practice. In order to employ these drugs in an
      individualized and precise medical manner and considering their efficacy and side
      effects, it seems worthwhile to learn the so far known mode of action and
      background history. Fumaric acid, as one of the newest drugs approved for MS,
      reveals the longest history as it was in use for decades as a treatment in
      psoriasis patients. Furthermore, fumaric acid is a good example for so far not
      extensively exploited option of drug reposition in medicine in general. The
      current review summarizes the outcomes of the clinical approval studies of
      fumaric acid in MS and discusses the dual mode of action, the immunomodulatory
      and tissue protective effect, as well as the reported adverse events under
      fumaric acid treatment. This review aims to serve an aid in the daily decision
      making practice when choosing the baseline therapy for MS patients. 

PMID- 24668401
TI  - [The new financial compensation system PEPP: an ethical analysis].
AB  - BACKGROUND: The new compensation system for psychiatric and psychosomatic
      institutions (German acronym: PEPP) not only constitutes a change in billing
      practices, but also necessitates an ethical investigation and analysis of
      possible consequences of the new legislation for those affected in practice.
      MATERIAL AND METHODS: Following the presentation of the new PEPP and its
      consequences for psychiatric practice, problems and areas of conflict will be
      analyzed from an ethical perspective and discussed. RESULTS: Ethical conflicts
      exist in the following areas: (1) in the attempt to standardize inpatient care
      and invoicing for mental illnesses, (2) in poorer treatment for severely ill
      patients in view of degressive per diem rates, (3) in false incentives due to
      threshold values e.g. for 1:1 health professional-patient ratios in the case of
      coercive measures and (4) due to the inappropriate use of a supposed normative
      neutral quantitative economic model for a qualitative work area that often takes
      place in human border zones such as complex inpatient care of severely mentally
      ill patients. CONCLUSION: The ethical analysis of PEPP reveals that apart from
      the limited opportunities to improve efficiency, there is a considerable ethical
      risk of loss of quality in psychiatric inpatient care in particular for severely
      and chronically mentally ill patients.

PMID- 24668403
TI  - [Behavioral excesses are symptom behaviours of heterogeneous etiology].

PMID- 24668402
TI  - [Paraneoplastic neurological syndromes and autoimmune encephalitis].
AB  - Paraneoplastic neurological syndromes (PNS) are defined as remote effects on the
      central and peripheral nervous system that are not caused directly by the tumor,
      its metastases and treatment, or metabolic disorders. The most probable cause is
      a falsely initiated immune reaction. Well-defined classical PNSs are associated
      with distinct tumors and occur with onconeural antibodies directed against
      intracellular neuronal antigens. However, response to therapy is limited.
      Recently, new antibodies directed against neuronal surface antigens were
      described in encephalitic syndromes of autoimmune origin. These probably antibody
      mediated disorders are more frequent than classical PNS, occur with or without
      tumor association and often show a good response to immunosuppressive treatment. 

PMID- 24668404
TI  - Structures and electro-optical properties of Mobius [n]Cyclacenes[13-18]: a
      theoretical study.
AB  - Due to the unusual properties of the Mobius cyclacenes (MC) such as pi electrons,
      MC has drawn the extensive attention of scientists. In the present work, six
      [n]MC (n  = 13-18, n is the number of benzenoid rings) were systematically
      investigated to explore the size-dependent effects on structures, electro-optical
      properties, and frontier molecule orbits (FMO). According to the dihedral angles
      (C-C-C-C), the un-twisted area and twisted area are defined, respectively. The
      twisted area mainly distributes on seven or eight benzenoid rings for [n]MC (n  =
      13-18). Further, the polarizability (alpha0) and first hyperpolarizability
      (beta0) of [n]MC (n  = 13-18) were calculated with three density functional
      methods (BHandHLYP, Cam-B3LYP, and M06-2X). Results show that the alpha0 values
      increase linearly with increasing the number (n) of benzenoid rings.
      Significantly, the beta0 values are increased to zigzag with increasing the
      number (n) of benzenoid rings. Interestingly, when n is even (14, 16, and 18),
      the electron transfer is from the twisted area to the un-twisted area, but the
      electron transfer is from the un-twisted area to the twisted area when n is odd
      (13, 15, and 17).

PMID- 24668405
TI  - Microfluidic approaches for epithelial cell layer culture and characterisation.
AB  - In higher eukaryotes, epithelial cell layers line most body cavities and form
      selective barriers that regulate the exchange of solutes between compartments. In
      order to fulfil these functions, the cells assume a polarised architecture and
      maintain two distinct plasma membrane domains, the apical domain facing the lumen
      and the basolateral domain facing other cells and the extracellular matrix.
      Microfluidic biochips offer the unique opportunity to establish novel in vitro
      models of epithelia in which the in vivo microenvironment of epithelial cells is
      precisely reconstituted. In addition, analytical tools to monitor biologically
      relevant parameters can be directly integrated on-chip. In this review we
      summarise recently developed biochip designs for culturing epithelial cell
      layers. Since endothelial cell layers, which line blood vessels, have similar
      barrier functions and polar organisation as epithelial cell layers, we also
      discuss biochips for culturing endothelial cell layers. Furthermore, we review
      approaches to integrate tools to analyse and manipulate epithelia and endothelia
      in microfluidic biochips; including methods to perform electrical impedance
      spectroscopy; methods to detect substances undergoing trans-epithelial transport
      via fluorescence, spectrophotometry, and mass spectrometry; techniques to
      mechanically stimulate cells via stretching and fluid flow-induced shear stress;
      and methods to carry out high-resolution imaging of vesicular trafficking using
      light microscopy. Taken together, this versatile microfluidic toolbox enables
      novel experimental approaches to characterise epithelial monolayers. 

PMID- 24668406
TI  - Colon polyp model use for educating about colorectal cancer screening in the Iowa
      Research Network.
AB  - Providing a model of a colon segment with an adenomatous polyp and cancer can
      help to educate patients about the adenoma to carcinoma sequence and how this
      sequence can be interrupted with appropriate testing. The purpose of this study
      was to assess the use of a three-dimensional colon model with polyps and cancer
      provided to family physicians or nurses in some Iowa Research Network family
      physician offices. Colon models were provided to 117 family medicine healthcare
      providers interested in colorectal cancer screening. Using a mailed survey and
      follow-up telephone calls to non-responders, 81 (69%) questionnaires were
      returned. Thirty-six (44%) of the respondents reported they had used the model,
      33 (41%) reported they used the model for a mean 16% of their patients in a
      month's time, 31 (38%) reported using the model to teach patients about the colon
      and polyps prior to a colonoscopy. Other model use described by respondents
      included educating staff to promote patient willingness for colonoscopies,
      demonstrating the need for colon cancer screening, and teaching patients about
      annual fecal occult blood tests. Respondents agreed that anatomical models are
      helpful for patient education, the design of the colon model was good, and that
      it facilitated demonstration of colon polyps. Possible recommendations for an
      office-wide adoption of an anatomical model would be an in-service for all
      employees and a standard location for finding the model.

PMID- 24668407
TI  - Author's response to 'CAP and HCAP are different? An unresolved question'.

PMID- 24668409
TI  - Suboptimal glycaemic control enhances the risk of impaired prothrombotic state in
      youths with type 1 diabetes mellitus.
AB  - OBJECTIVE: To estimate markers of prothrombotic state and endothelial dysfunction
      in youths with type 1 diabetes mellitus (T1DM) and investigate possible
      associations with anthropometric/demographic data, glycaemic control and lipid
      profile. METHODS: In a cross-sectional design, we recruited 155 youths with T1DM
      and determined levels of plasminogen activator inhibitor-1-antigen (PAI-1-Ag),
      von Willebrand factor-antigen (vWF-Ag), fibrinogen (FB), lipids and glycosylated
      haemoglobin (HbA1c). RESULTS: Of all the participants, 76 (49%) had increased
      levels of at least one of prothrombotic factors. Suboptimal glycaemic control was
      associated with a worse lipid profile and an eightfold increased risk of elevated
      vWF-Ag levels. Higher vWF-Ag concentrations were also correlated with impaired
      lipid profile and increased HbA1c values, whereas PAI-1-Ag was positively
      correlated only with triglyceride levels. After adjustment for potential
      confounders, only HbA1c contributed independently to the variation in vWF-Ag
      levels. CONCLUSION: Impaired prothrombotic state and consequently endothelial
      dysfunction are present in youths with T1DM, representing a cumulative risk
      factor for future cardiovascular disease (CVD). Achievement and maintenance of
      euglycaemia and normolipidaemia are crucial to decelerate progress of this
      process.

PMID- 24668408
TI  - The genomic origins of asthma.
AB  - Lung function tracks from the earliest age that it can be reliably measured.
      Genome wide association studies suggest that most variants identified for common
      complex traits are regulatory in function and active during fetal development.
      Fetal programming of gene expression during development is critical to the
      formation of a normal lung. An understanding of how fetal developmental genes
      related to diseases of the lungs and airways is a critical area for research.
      This review article considers the developmental origins hypothesis, the stages of
      normal lung development and a variety of environmental exposures that might
      influence the developmental process: in utero cigarette smoke exposure, vitamin D
      and folate. We conclude with some information on developmental genes and asthma. 

PMID- 24668410
TI  - Vegetation placement for summer built surface temperature moderation in an urban
      microclimate.
AB  - Urban vegetation can mitigate increases in summer air temperature by reducing the
      solar gain received by buildings. To quantify the temperature-moderating
      influence of city trees and vine-covered buildings, a total of 13 pairs of
      temperature loggers were installed on the surfaces of eight buildings in downtown
      Toronto, Canada, for 6 months during the summer of 2008. One logger in each pair
      was shaded by vegetation while the other measured built surface temperature in
      full sunlight. We investigated the temperature-moderating benefits of solitary
      mature trees, clusters of trees, and perennial vines using a linear-mixed model
      and a multiple regression analysis of degree hour difference. We then assessed
      the temperature-moderating effect of leaf area, plant size and proximity to
      building, and plant location relative to solar path. During a period of high
      solar intensity, we measured an average temperature differential of 11.7  degrees
      C, with as many as 10-12 h of sustained cooler built surface temperatures.
      Vegetation on the west-facing aspect of built structures provided the greatest
      temperature moderation, with maximum benefit (peak temperature difference)
      occurring late in the afternoon. Large mature trees growing within 5 m of
      buildings showed the greatest ability to moderate built surface temperature, with
      those growing in clusters delivering limited additional benefit compared with
      isolated trees. Perennial vines proved as effective as trees at moderating rise
      in built surface temperature to the south and west sides of buildings, providing
      an attractive alternative to shade trees where soil volume and space are limited.

PMID- 24668411
TI  - Ripping improves tree survival and growth on unused reclaimed mined lands.
AB  - There is renewed interest in re-establishing trees on 0.6 million ha of mining
      disturbed lands in the Appalachian mountains of Eastern United States. Many coal
      mined lands reclaimed to meet requirements of US federal law have thick
      herbaceous vegetation and compacted soils which impede tree establishment.
      Mitigation practices were applied on three mine sites and evaluated for success
      in enabling planted trees to become established. Eastern white pine (Pinus
      strobus), hybrid poplar (Populus deltoids * Populus trichocarpa), and mixed
      Appalachian hardwoods were established using weed control only and weed control
      with subsoil ripping. Trees were measured in October of 2008 after 5 years of
      growth. Subsoil ripping increased mixed hardwood survival from 43 to 71%, hybrid
      poplar biomass index from 1.51 to 8.97 Mg ha(-1), and Eastern white pine biomass
      index from 0.10 to 0.32 Mg ha(-1). When restoring trees to unused mined sites,
      subsoil ripping can aid survival and growth to an extent that will result in a
      valuable forest.

PMID- 24668412
TI  - Activity of anti-cancer protein kinase inhibitors against Leishmania spp.
AB  - OBJECTIVES: There is an urgent need to develop new and effective treatments for
      poverty-related neglected diseases. In light of the time required to bring a new
      drug to market and the cost involved (10-15 years, >1 billion US$), one approach
      to identifying new treatments for diseases like leishmaniasis is to evaluate
      drugs that are already registered for the treatment of other diseases. This paper
      describes the anti-leishmanial activities of 10 FDA-approved protein kinase
      inhibitors already available for the treatment of human cancers. METHODS: In
      vitro and in vivo models of Leishmania infection were used to evaluate the
      potency of selected protein kinase inhibitors. RESULTS: Sunitinib, sorafenib and
      lapatinib were identified as active against Leishmania donovani amastigotes in
      cultured murine macrophages with IC(50) values of 1.1, 3.7 and 2.5 MUM,
      respectively, a level of potency similar to that of miltefosine (IC(50) = 1.0
      MUM), and were not toxic to mammalian cells. In addition, some of the protein
      kinase inhibitors were active against L. donovani in the BALB/c mouse model of
      infection; dosing on days 7-11 with a 50 mg/kg oral dose of sunitinib, lapatinib
      or sorafenib reduced liver amastigote burdens by 41%, 36% and 30%, respectively,
      compared with untreated control mice. Although less efficacious, sorafenib was
      also active in vitro against intracellular amastigotes of the cutaneous disease
      causing species Leishmania amazonensis, Leishmania major and Leishmania mexicana.
      CONCLUSIONS: This study demonstrates in vivo anti-leishmanial activity of
      clinically used protein kinase inhibitors and provides further evidence of the
      potential of drug repurposing.

PMID- 24668413
TI  - Aggregation dynamics, structure, and mechanical properties of bigels.
AB  - Recently we have introduced bigels, inter-penetrating gels made of two different
      colloidal species. Even if particles with simple short-range isotropic potential
      are employed, the selective interactions enable the tunability of the self
      assembly, leading to the formation of complex structures. In the present paper,
      we explore the non-equilibrium dynamics and the phenomenology underlying the
      kinetic arrest under quench and the formation of bigels. We demonstrate that the
      peculiar bigel kinetics can be described through an arrested spinodal
      decomposition driven by demixing of the colloidal species. The role played by the
      presence of a second colloidal species on the phase diagram, as expanded to
      account for the increased number of parameters, is clarified both via extensive
      numerical simulations and experiments. We provide details on the realisation of
      bigels, by means of DNA-coated colloids (DNACCs), and the consequent imaging
      techniques. Moreover we evidence, by comparison with the usual one-component gel
      formation, the emergence of controllable timescales in the aggregation of the
      bigels, whose final stages are also experimentally studied to provide
      morphological details. Finally, we use numerical models to simulate the bigel
      response to mechanical strain, highlighting how such a new material can bear
      significantly higher stress compared to the usual one-component gel. We conclude
      by discussing possible technological uses and by providing insights on the viable
      research steps to undertake for more complex and yet tuneable multi-component
      colloidal systems. 

PMID- 24668414
TI  - The wisdom of Sherwin Nuland.

PMID- 24668415
TI  - Relationship between concentrations of IGF-1 and IGFBP-3 and preoperative
      depression risk, and effect of psychological intervention on outcomes of high
      grade glioma patients with preoperative depression in a 2-year prospective study.
AB  - Growth factors in the brain are important to depression. We investigated the
      relationship between serum insulin-like growth factor (IGF-1) and IGF-binding
      protein-3 (IGFBP-3) concentration and risk of depression and the effect of
      psychological intervention on outcomes of high-grade glioma patients with
      preoperative depression. A total of 249 high-grade glioma patients participated
      in blood sample collection for IGF-1 and IGFBP-3 detection by ELISA and the
      Hospital Anxiety and Depression Scale testing. The association between IGF-I or
      IGFBP-3 and depression risk was assessed using conditional logistic regression,
      and Student's t tests were used to evaluate differences in change of the
      Karnofsky Performance Status Scale (KPS) in subgroups after performance of
      psychosocial intervention. The survivals of patients in subgroups were tested by
      Kaplan-Meier (log-rank test). We found the risk of depression was elevated with
      increased IGF-I (HR = 6.320, 95% CI 2.456-16.265, top vs. bottom quartile) and
      IGFBP-3 concentrations (HR = 3.411, 95% CI 1.345-8.648) after adjustment of
      confounders. KPS was increased significantly in the intervention groups, but not
      significantly in the usual care groups after performance of psychosocial
      intervention. The survival of depressed patients in the usual group was
      significantly worse than those of other subgroups after performance of
      psychosocial intervention. Depression is prevalent among patients with high-grade
      gliomas, and factors of the IGF axis are positively associated with risk of
      depression and might be involved in the etiology of depression in high-grade
      glioma patients. Depression correlates with quality of life and outcomes of
      patients. Therefore, some psychological interventions are needed and may help
      patients to relieve depression and improve the life quality of glioma patients.

PMID- 24668416
TI  - miR-99a and -99b inhibit cervical cancer cell proliferation and invasion by
      targeting mTOR signaling pathway.
AB  - MicroRNAs were demonstrated to play an important role in the regulation of gene
      expression. Here, we showed that miR-99a and -99b (miR-99a/b) were down-regulated
      in human cervical cancer patient tissues and were negatively related with
      lymphatic metastasis. In addition, overexpression of miR-99a/b inhibited cell
      growth and invasion, whereas suppression of miR-99a/b yielded the reverse
      phenotype. Dual luciferase report assay revealed that mTOR was identified as a
      novel target gene of both miR-99a and -99b. Altogether, these results suggested
      that miR-99a/b directly and negatively regulated mTOR expression in cervical
      cancer cells, and enforced the importance of miR-99a/b and their targets in the
      malignant phenotypes of cervical carcinogenesis. 

PMID- 24668417
TI  - Distribution of microsomal prostaglandin E synthase-1 in the mouse brain.
AB  - Previous studies in rats have demonstrated that microsomal prostaglandin E
      synthase-1 (mPGES-1) is induced in brain vascular cells that also express
      inducible cyclooxygenase-2, suggesting that such cells are the source of the
      increased PGE2 levels that are seen in the brain following peripheral immune
      stimulation, and that are associated with sickness responses such as fever,
      anorexia, and stress hormone release. However, while most of what is known about
      the functional role of mPGES-1 for these centrally evoked symptoms is based on
      studies on genetically modified mice, the cellular localization of mPGES-1 in the
      mouse brain has not been thoroughly determined. Here, using a newly developed
      antibody that specifically recognizes mouse mPGES-1 and dual-labeling for cell
      specific markers, we report that mPGES-1 is constitutively expressed in the mouse
      brain, being present not only in brain endothelial cells, but also in several
      other cell types and structures, such as capillary-associated pericytes,
      astroglial cells, leptomeninges, and the choroid plexus. Regional differences
      were seen with particularly prominent labeling in autonomic relay structures such
      as the area postrema, the subfornical organ, the paraventricular hypothalamic
      nucleus, the arcuate nucleus, and the preoptic area. Following immune
      stimulation, mPGES-1 in brain endothelial cells, but not in other mPGES-1
      positive cells, was coexpressed with cyclooxygenase-2, whereas there was no
      coexpression between mPGES-1 and cyclooxygenase-1. These data imply a widespread
      synthesis of PGE2 or other mPGES-1-dependent products in the mouse brain that may
      be related to inflammation-induced sickness symptom as well as other functions,
      such as blood flow regulation.

PMID- 24668418
TI  - Structural characterization of dissolved organic matter: a review of current
      techniques for isolation and analysis.
AB  - Natural dissolved organic matter (DOM) in aquatic systems plays many
      environmental roles: providing building blocks and energy for aquatic biota,
      acting as a sunscreen in surface water, and interacting with anthropogenic
      compounds to affect their ultimate fate in the environment. Such interactions are
      a function of DOM composition, which is difficult to ascertain due to its
      heterogeneity and the co-occurring matrix effects in most aquatic samples. This
      review focuses on current approaches to the chemical structural characterization
      of DOM, ranging from those applicable to bulk samples and in situ analyses (UV
      visible spectrophotometry and fluorescence spectroscopy) through the
      concentration/isolation of DOM followed by the application of one or more
      analytical techniques, to the detailed separation and analysis of individual
      compounds or compound classes. Also provided is a brief overview of the main
      techniques used to characterize isolated DOM: mass spectrometry (MS), nuclear
      magnetic resonance mass spectrometry (NMR) and Fourier transform infrared
      spectroscopy (FTIR). 

PMID- 24668419
TI  - Qualitative and Quantitative Analysis of Interviewer Help Answering the Time
      Tradeoff.
AB  - OBJECTIVES: The time tradeoff (TTO) is an important method to directly obtain
      health utilities. Challenges of the TTO are, among others, "nontraders" and
      illogical answers. In TTO interviews, these challenges are resolved by the
      interviewer. In web-based TTOs, training procedures and logical checks are used
      based on the views of the researchers. As web-based TTOs will be used more often
      in the future, we investigated how respondents arrive at their ratings to
      determine the help they require. METHODS: In 2 earlier studies performed by this
      research group, respondents valued 6 EQ-5D states on a TTO. Respondents were
      asked to think out loud, and all interviews were audiotaped. A random selection
      of these interviews were transcribed and double-coded by two independent raters,
      using a priori and inductive coding until saturation was reached. Based on the
      retrieved mistakes and comments, a list of frequently asked questions (FAQ) was
      developed. RESULTS: In total, 91 interviews were coded. In all, 85% made at least
      1 mistake, 41% made a misreading/miscalculation, 70% misunderstood the tradeoff,
      27% misunderstood the EQ-5D dimensions, 29% misunderstood the scenario, 45% made
      a comment about the TTO, and 43% expressed frustration. More misunderstandings
      were reported in the Peeters study, which was performed in a realistic setting,
      whereas the van Osch study was conducted in a more ideal setting.
      Misunderstandings of the scenario were mosly reported by patients. CONCLUSIONS:
      Almost all respondents need interviewer help. This may have implications for the
      validity of interviewer-based TTO elicitations when social acceptability bias is
      an issue or with explicit hypothesis and the interviewer is not blinded. The FAQ
      list can be used to standardize interviewer help or as a help function in a web
      based TTO.

PMID- 24668420
TI  - 7,7,8,8-Tetracyanoquinodimethane-assisted one-step electrochemical exfoliation of
      graphite and its performance as an electrode material.
AB  - A green approach for the preparation of water-dispersible functionalized graphene
      via one-step electrochemical exfoliation of graphite using 7,7,8,8
      tetracyanoquinodimethane (TCNQ) anions as surface modifiers and electrolytes was
      described. TCNQ is an organic charge-transfer complex with electron accepting and
      noteworthy electrical properties. The exfoliation of graphite to a few-layer
      graphene sheets was confirmed by transmission electron microscopy (TEM) and
      atomic force microscopy (AFM) image analysis. The chemical state, surface
      functional groups and chemical compositions of bulk graphite as well as TCNQ
      functionalized graphene sheets were investigated by Fourier-transform infrared
      (FT-IR) and X-ray photoelectron spectroscopy (XPS) analysis. Adsorption of TCNQ
      onto the surface of graphene sheets was confirmed by the appearance of the N1s
      peak at ~399.4 eV in the XPS of TCNQ-functionalized graphene. Exfoliation of bulk
      graphite to functionalized graphene sheets was further confirmed by the
      appearance of a sharp single peak at ~2695 cm(-1) along with increased intensity
      ratios of the D-band to the G-band. Electrochemical performance of a TCNQ
      functionalized graphene sheet was investigated using 1 M Na2SO4 and 1 M KOH
      aqueous solutions. Cyclic voltammetry (CV) and galvanometric charge-discharge
      experiments revealed that TCNQ-functionalized graphene could be used as a
      supercapacitor electrode material. The specific capacitance values of TCNQ
      modified graphene measured with electrolytes (1 M KOH and 1 M Na2SO4) were 324
      and 140 F g(-1), respectively, at a current density of 1 A g(-1). Impedance
      spectroscopic analysis revealed that the charge transfer process was dependent on
      surface functionalization and interaction between the electrode and the
      electrolyte. 

PMID- 24668422
TI  - Liquid state dynamic nuclear polarization of ethanol at 3.4 T (95 GHz).
AB  - Dynamic Nuclear Polarization (DNP) in the liquid state has become the focus of
      attention to improve the NMR sensitivity of mass limited samples. The Overhauser
      model predicts a fast reduction in DNP enhancement at high magnetic fields where
      the electron Larmor frequency exceeds the typical inverse correlation time of the
      magnetic interaction between an unpaired electron spin of a radical and proton
      spins of the solvent molecules. The Overhauser hard sphere model is able to
      predict quantitatively the DNP enhancement for water TEMPOL solutions. The
      increase in temperature due to dielectric heating of the sample acts to reduce
      the correlation times and allows a substantial Overhauser DNP. In this paper we
      extend the work done on water towards other small molecules, such as ethanol.
      Experimentally we observe a similar enhancement for all three proton groups in
      the ethanol molecule. The classical interpretation of the low field Overhauser
      experiments on ethanol invokes a very fast anisotropic rotation of the hydrogen
      bonded TEMPOL-ethanol complex to explain the fast relaxation of the OH proton.
      Here we will discuss W-band relaxation and DNP enhancement within this classical
      model. Although the description can be made quantitative, the invoked parameters
      do not seem to be realistic. We will propose an alternative model based on the
      dynamic interaction both in free collision and due to modulation of the hydrogen
      bond length of the complex. 

PMID- 24668421
TI  - "Live High-Train High" increases hemoglobin mass in Olympic swimmers.
AB  - PURPOSE: This study tested whether 3-4 weeks of classical "Live High-Train High"
      (LHTH) altitude training increases swim-specific VO2max through increased
      hemoglobin mass (Hbmass). METHODS: Ten swimmers lived and trained for more than 3
      weeks between 2,130 and 3,094 m of altitude, and a control group of ten swimmers
      followed the same training at sea-level (SL). Body composition was examined using
      dual X-ray absorptiometry. Hbmass was determined by carbon monoxide rebreathing.
      Swimming VO2peak was determined and swimming trials of 4 * 50, 200 and 3,000 m
      were performed before and after the intervention. RESULTS: Hbmass (n = 10) was
      increased (P < 0.05)after altitude training by 6.2 +/- 3.9 % in the LHTH group,
      whereas no changes were apparent in the SL group (n = 10). Swimming VO2peak was
      similar before and after training camps in both groups (LHTH: n = 7, SL: n = 6).
      Performance of 4 * 50 m at race pace was improved to a similar degree in both
      groups (LHTH: n = 10, SL: n = 10). Maximal speed reached in an incremental
      swimming step test (P = 0.051), and time to complete 3,000 m tended (P = 0.09) to
      be more improved after LHTH (n = 10) than SL training (n = 10). CONCLUSION: In
      conclusion, 3-4 weeks of classical LHTH is sufficient to increase Hbmass but
      exerts no effect on swimming-specific VO2peak. LHTH may improve performance more
      than SL training.

PMID- 24668423
TI  - Phenolic characterization and antimicrobial activity of folk medicinal plant
      extracts for their applications in olive production.
AB  - Phytophthora spp is important in plant pathology due to the importance of the
      diseases it causes. In olive trees, severe damages are caused by the disease
      known as "dry branch" occasioned by Phytophthora nicotianae, P. citrophthora and
      P. palmivora. Much effort has been made to find efficient methods of control,
      with a low negative impact on environment. In this regard, treatment with plant
      extracts is a valid strategy. The aims of the present study are (i) to determine
      the polyphenol composition of extracts of Thymus vulgaris, Origanum vulgare,
      Matricaria recutita, and Larrea divaricata by CZE, (ii) correlate the analytical
      composition of these extracts with the inhibition on the mycelial growth, and
      (iii) determine the individual antimicrobial activity of the most active
      ingredients. A simple methodology was developed for the determination of
      catechin, naringenin, cinnamic acid, syringic acid, chlorogenic acid, apigenin,
      vanillic acid, luteolin, quercetin, and caffeic acid in plant extracts by CZE.
      The extraction of phenolic compounds in extract was performed by a miniaturized
      solid phase extraction using a home-made minicolumn packed with suitable
      filtering material (C18 , 50 mg). The optimized analyses conditions were: 30 mM
      boric acid buffer, pH 9.50; capillary, 57 cm full length, 50 cm effective length,
      75 MUm id, hydrodynamic injection 30 mbar, 2 s; 25 kV; 25 degrees C, detection by
      UV absorbance at 290 nm. Sample results suggest that phenolic composition seems
      to have a great influence on inhibition of pathogens. The highest inhibitions of
      mycelial growth were observed for cinnamic acid and naringenin.

PMID- 24668425
TI  - [Internists between the poles of high-quality patient care and economic
      requirements].

PMID- 24668424
TI  - Variations in microanatomy of the human cochlea.
AB  - The human cochlea shows considerable interindividual variability in size and
      morphology. In order to develop atraumatic cochlear implant (CI) electrodes, high
      precision details of the variability of human anatomy are required. Sixteen human
      temporal bones were cut around the cochlea in blocks of approximately 3.5 * 3.5
      cm. The bones were scanned by using a Skyscan 1173 micro-computed tomography
      (MUCT) device. Mimics software (Materialise, Leuven, Belgium) was used to segment
      out the scala tympani (ST) from the MUCT images. A three-dimensional surface
      model of the segmented area was generated for each cochlea. Cross-sectional
      images were taken and analyzed by custom-designed software in MATLAB. Comparison
      of different STs showed large variability in cross-sectional diameter (CSD),
      vertical trajectory, and height of the ST. Relative standard deviations of the
      CSD were between 9 and 15%. Heights measured at the center of the ST exceeded
      those in the modiolar and lateral regions of the scala. At the lateral region,
      the height decreased significantly at the beginning of the second turn. In the
      vertical trajectory, critical anatomic features were observed, such as dips,
      vertical jumps, and peaks. Rosenthal's canal (RC) extended to between 560 and 650
      degrees . We found a correlation between the length of the RC and that of the ST.
      The ST was segmented and the internal dimensions measured by using MUCT. We
      observed large dimensional variability between different STs. These differences
      could have considerable implications for approaches to the design of CI arrays,
      especially in terms of their ability to preserve residual hearing during
      insertion of the electrode array.

PMID- 24668426
TI  - [Antithrombotic treatment after peripheral arterial surgery].

PMID- 24668427
TI  - [Circadian clocks and energy metabolism: implications for health].
AB  - On behavioural as well as physiological levels our daily life is regulated by the
      circadian clock - endogenous oscillators present in the hypothalamus and in
      peripheral tissues - which is believed to have evolved as an adaptation to Earth
      rotation around the Sun and its consequent 24 h dark-light cycle. Accumulative
      evidence suggests that the circadian clock plays a pivotal role for energy
      metabolism and energy homeostasis: many hormones, enzymes and transport systems
      involved in the regulation of energy metabolism have been shown to display
      circadian rhythms in their expression, secretion and/or activity patterns. The
      energy metabolism, in turn, can impact on the circadian clock - a process that is
      called entrainment. Thus, the circadian clock and energy metabolism are
      intimately intertwined. So far this interplay and its implications for health
      have not been understood very well. For health maintenance, however, it seems to
      be crucial to avoid any desynchronisation between the circadian clock and energy
      metabolism. Form a clinical point of view this might be important for the
      treatment of obesity and associated disorders and may lead to new life-style
      approaches.

PMID- 24668428
TI  - [Prevention of catheter-related septicemia].

PMID- 24668429
TI  - [Coronary stents: what is new?].

PMID- 24668430
TI  - [Diabetic nephropathy: new insights into diagnosis, prevention and treatment].

PMID- 24668432
TI  - [Connective tissue diseases].

PMID- 24668431
TI  - [Non-cystic fibrosis bronchiectasis [corrected]].

PMID- 24668433
TI  - [Arterial hypertension - new target values].

PMID- 24668434
TI  - [81-year-old woman with remarkable serum electrophoresis].

PMID- 24668435
TI  - [HIV: what is to be done after occupational and non occupational exposition?].

PMID- 24668436
TI  - [Mounier-Kuhn syndrome - a rare cause of recurrent bronchitis].
AB  - HISTORY AND ADMISSION FINDINGS: A 43-year-old man presented at our emergency room
      with progressive dyspnea and productive cough. He was in moderate respiratory
      distress. Symptomatic treatment had so far not led to clinical improvement. He
      had suffered from similar episodes since adolescence. INVESTIGATIONS: An
      intensive diagnostic investigation was started to evaluate the source of
      infection and dyspnea. CRP levels were elevated to 26 mg/l. Arterial blood gas
      analysis showed a moderate hypoxemia with a pO2 of 8.35kPa (63 mmHg) and a pCO2
      of 3.84kPa (29 mmHg). DIAGNOSIS, TREATMENT AND COURSE: Computed tomography of the
      chest revealed the diagnosis of trachebobronchomegaly. This rare cause of
      recurrent bronchitis is named after Mounier-Kuhn who established this diagnosis
      for the first time. The patient improved under a course with antibiotics and
      inhaled bronchodilators. CONCLUSION: In patients with recurrent bronchitis, an
      underlying disease of the tracheobronchial system has to be suspected. The
      Mounier-Kuhn syndrome is only rarely diagnosed because the diagnosis cannot be
      established by conventional chest x-ray. Computed tomography is the gold standard
      for diagnosis. Mounier-Kuhn syndrome is likely to lead to severe venilatory
      failure and death, if untreated.

PMID- 24668437
TI  - ["Physicians/Managers 2013": a study of the German Society of Internal Medicine].

PMID- 24668438
TI  - [Pain management of cognitively impaired patients].
AB  - Pain is a significant problem in clinical practice and its control is one of the
      most important challenging aspects as pain has a major impact on patients'
      quality of life and health care costs. Particularly vulnerable persons, like
      cognitively impaired patients are challenging for pain management and underline
      its increasing relevance.National and international studies showed significant
      differences concerning pain therapy between cognitively impaired and cognitively
      intact patients. A possible cause of this may be that patients who are
      cognitively impaired are only in a restricted way able to express their pain.
      Furthermore, knowledge gaps and reservations concerning the effect and dosage of
      analgesics among cognitively impaired patients could be identified on the
      involved professions.Further investigations in Germany are needed as deficient
      treatment remains a persistent problem and evidence-based data are missing. These
      investigations should describe the status quo of pain management for cognitively
      impaired patients and provide information which processes have to be adapted to
      the needs of these vulnerable patients. 

PMID- 24668439
TI  - Microfluidic platform for negative enrichment of circulating tumor cells.
AB  - Negative enrichment is the preferred approach for tumor cell isolation as it does
      not rely on biomarker expression. However, size-based negative enrichment methods
      suffer from well-known recovery/purity trade-off. Non-size based methods have a
      number of processing steps that lead to compounded cell loss due to extensive
      sample processing and handling which result in a low recovery efficiency. We
      present a method that performs negative enrichment in two steps from 2 ml of
      whole blood in a total assay processing time of 60 min. This negative enrichment
      method employs upstream immunomagnetic depletion to deplete CD45-positive WBCs
      followed by a microfabricated filter membrane to perform chemical-free RBC
      depletion and target cells isolation. Experiments of spiking two cell lines, MCF
      7 and NCI-H1975, in the whole blood show an average of >90 % cell recovery over a
      range of spiked cell numbers. We also successfully recovered circulating tumor
      cells from 15 cancer patient samples. 

PMID- 24668441
TI  - Photoactuation and thermal isomerisation mechanism of cyanoazobenzene-based
      liquid crystal elastomers.
AB  - 4-Alkoxy-4'-cyanoazobenzenes are organic chromophores with great applicability
      within present nanotechnology. However, the use of such azo dyes for obtaining
      light-triggered artificial muscle-like actuators remains still unexplored.
      Achieving further knowledge about the thermal back reaction and isomerisation
      mechanism for these types of azoderivatives is essential to get photo-actuators
      with the desired abilities. Despite the push-pull nature of the 4-alkoxy-4'
      cyanoazobenzene chromophore, it has been experimentally demonstrated that it
      isomerises via an inversion mechanism. The opto-mechanics of the prepared
      elastomeric material has also been investigated. For this system, a maximum opto
      mechanical response of ca. 2.5 kPa has been registered, which is independent of
      the working temperature of the photoactuator. 

PMID- 24668440
TI  - The discriminative stimulus effects of the neurotensin NTS1 receptor agonist
      PD149163 in rats: stimulus generalization testing with dopamine D1 and D2
      receptor ligands.
AB  - Brain-penetrant neurotensin NTS1 receptor agonists produce antipsychotic drug
      like effects in animal models, including inhibition of conditioned avoidance
      responding and reversal of psychostimulant-induced hyperactivity and stereotypy.
      Allosteric interactions between NTS1 receptors and dopamine D2 receptors may
      account for some of these antipsychotic effects. In order to determine the role
      that dopamine receptors may play in the behavioral effects produced by activation
      of NTS1 receptors, a drug discrimination approach was used in rats to evaluate
      the potential mediation of NTS1 receptor agonist stimulus effects by dopamine D1
      and D2 receptors. Rats were trained to discriminate either the NTS1 receptor
      agonist PD149163, the D1 receptor agonist SKF81297, or the D2 receptor agonist
      quinpirole from vehicle in a two choice drug discrimination task. Full stimulus
      generalization occurred from PD149163 to the typical antipsychotic drug and D2
      receptor-preferring antagonist haloperidol. However, stimulus generalization did
      not occur from SKF81297 or quinpirole to PD149163. The discriminative cue for
      SKF91297 and quinpirole was fully blocked the D1 receptor antagonist SCH23390 and
      the D2/3 receptor antagonist raclopride, respectively. Cross generalization did
      not occur between SKF91297 and quinpirole. Based on these findings, the stimulus
      effects of PD149163 may be mediated, in part, through D2 receptor antagonism, but
      this may only be evident when PD149163 is used as the training drug.

PMID- 24668442
TI  - Validation of international consensus guidelines for the resection of branch duct
      type intraductal papillary mucinous neoplasms.
AB  - BACKGROUND: Classifications of intraductal papillary mucinous neoplasm (IPMN)
      remain ambiguous, especially for the mixed type. Factors predicting malignancy
      remain unclear. The aim of this study was to evaluate the usefulness of factors
      predicting malignancy in the new international consensus guidelines for resection
      of branch duct-type (BD)-IPMN and to compare them with those in the previous
      version. METHODS: A prospectively collected database of patients with biopsy
      proven BD-IPMN was analysed to compare factors between the first and second
      consensus guidelines, particularly as predictors of malignancy. RESULTS: Of 350
      patients with BD-IPMN, sensitivity (0.724) and balanced accuracy (0.751) of the
      second guidelines were superior to those (0.639 and 0.730) in the first version
      at the expense of slightly reduced specificity (0.779 versus 0.822 for the first
      version) by random forest models. Multiple logistic regression analysis showed
      that main pancreatic duct dilatation greater than 5 mm (hazard ratio (HR) 4.54,
      95 per cent confidence interval 2.45 to 8.41; P < 0.001), mural nodules (HR 6.27,
      3.27 to 12.01; P < 0.001) and carbohydrate antigen 19-9 level above 37 units/ml
      (HR 4.03, 1.83 to 8.90; P = 0.001) were independent predictors of BD-IPMN
      malignancy. CONCLUSION: The new consensus guidelines provide better sensitivity,
      performance of factors predicting malignancy, and balanced accuracy in the
      diagnosis of BD-IPMN malignancy. Size alone was limited in predicting malignancy.
      Variability in clinical significance of the individual factors associated with a
      risk of malignancy indicates the need for a tailored approach in the management
      of patients with BD-IPMN.

PMID- 24668443
TI  - Association studies using family pools of outcrossing crops based on allele
      frequency estimates from DNA sequencing.
AB  - KEY MESSAGE: We propose a method in which GBS data can be conveniently analyzed
      without calling genotypes. F2 families are frequently used in breeding of
      outcrossing species, for instance to obtain trait measurements on plots. We
      propose to perform association studies by obtaining a matching "family genotype"
      from sequencing a pooled sample of the family, and to directly use allele
      frequencies computed from sequence read-counts for mapping. We show that, under
      additivity assumptions, there is a linear relationship between the family
      phenotype and family allele frequency, and that a regression of family phenotype
      on family allele frequency will estimate twice the allele substitution effect at
      a locus. However, medium-to-low sequencing depth causes underestimation of the
      true allele substitution effect. An expression for this underestimation is
      derived for the case that parents are diploid, such that F2 families have up to
      four dosages of every allele. Using simulation studies, estimation of the allele
      effect from F2-family pools was verified and it was shown that the
      underestimation of the allele effect is correctly described. The optimal design
      for an association study when sequencing budget would be fixed is obtained using
      large sample size and lower sequence depth, and using higher SNP density
      (resulting in higher LD with causative mutations) and lower sequencing depth.
      Therefore, association studies using genotyping by sequencing are optimal and use
      low sequencing depth per sample. The developed framework for association studies
      using allele frequencies from sequencing can be modified for other types of
      family pools and is also directly applicable for association studies in
      polyploids.

PMID- 24668444
TI  - A disordered silver nanowires membrane for extraction and surface-enhanced Raman
      spectroscopy detection.
AB  - A disordered silver nanowires membrane combining solid-phase extraction (SPE)
      with surface-enhanced Raman spectroscopy (SERS) was used for the rapid collection
      and detection of food contaminants. The membrane was fabricated via filtration of
      the silver nanowires colloid solution, which was prepared by a solvothermal
      polyol process. Analytes in 5 mL of liquid phase were concentrated in less than
      10 s due to their affinity for the silver nanowires on the filter membrane. The
      membrane combined the advantages of SPE and SERS technology for the analysis of
      food safety contaminants. The use of the SERS-active extraction membrane
      eliminated the procedure of elution, which shortened the time of analysis. It has
      been shown that the as-prepared membrane had good uniformity and high temporal
      stability under continuous laser irradiation. Qualitative and quantitative
      detection of phorate and melamine was further performed based on a flow-through
      method. The characteristic SERS intensity plotted against phorate and melamine
      concentrations exhibited a good linear relationship over the concentration range
      of 2.5 to 10 MUg mL(-1) (phorate) and 2.5 to 100 MUg mL(-1) (melamine). 

PMID- 24668445
TI  - Functional brain interactions during reflexive micturition are absent from spinal
      cord injured rats with neurogenic bladder.
AB  - AIMS: The micturition reflex is initiated by urinary bladder distension
      triggering afferent pathways and activation of specific brain centers for
      controlling urine storage and release. We evaluated brain activation patterns
      using blood oxygenation level dependent functional magnetic resonance imaging
      (fMRI) during reflexive micturition in normal and spinal cord injury (SCI) rats.
      METHODS: Sprague-Dawley female rats, either intact or with complete spinal cord
      transection, were anesthetized with urethane for simultaneous isovolumetric
      cystometry (CMG) and fMRI evaluations. A 9.4-Tesla MRI system with a 4-elements
      receiver array and a quadrature volume transmit coil was used to maximize the
      sensitivity detection. Gradient echo-planar imaging (EPI) was used to evaluate
      brain activation during CMG compared to the empty bladder condition. Group
      analysis was conducted with a cluster threshold of Z > 2.5 and significance
      threshold of P = 0.05. RESULTS: The amplitude of bladder contractions was 10-fold
      higher in control rats and inter-contractile intervals were significantly shorter
      in SCI rats, indicative of neurogenic overactivity. Group analysis in intact rats
      showed both known and novel activation patterns in hippocampus, dentate gyrus,
      ectorhinal cortex, thalamic nucleus, septal nucleus, primary and secondary motor
      cortex, primary somatosensory cortex, and the periaqueductal gray matter. SCI
      rats did not exceed the Z-threshold during CMG. CONCLUSIONS: We standardized a
      suitable urodynamic protocol to study supraspinal activation during reflexive
      micturition using simultaneous CMG/fMRI with high spatial resolution. Small
      contractions in SCI rats may be caused by increased excitability of afferent
      pathways without brain activation. Our results represent the first fMRI study in
      SCI rats.

PMID- 24668446
TI  - The TRPA1 channel in inflammatory and neuropathic pain and migraine.
AB  - The transient receptor potential ankyrin 1 (TRPA1), a member of the TRP
      superfamily of channels, is primarily localized to a subpopulation of primary
      sensory neurons of the trigeminal, vagal, and dorsal root ganglia. This subset of
      nociceptors produces and releases the neuropeptides substance P (SP) and
      calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory
      responses. TRPA1 is activated by a number of exogenous compounds, including
      molecules of botanical origin, environmental irritants, and medicines. However,
      the most prominent feature of TRPA1 resides in its unique sensitivity for large
      series of reactive byproducts of oxidative and nitrative stress. Here, the role
      of TRPA1 in models of different types of pain, including inflammatory and
      neuropathic pain and migraine, is summarized. Specific attention is paid to TRPA1
      as the main contributing mechanism to the transition of mechanical and cold
      hypersensitivity from an acute to a chronic condition and as the primary
      transducing pathway by which oxidative/nitrative stress produces acute
      nociception, allodynia, and hyperalgesia. A series of migraine triggers or
      medicines have been reported to modulate TRPA1 activity and the ensuing CGRP
      release. Thus, TRPA1 antagonists may be beneficial in the treatment of
      inflammatory and neuropathic pain and migraine. 

PMID- 24668447
TI  - Total synthesis of monosporascone and dihydromonosporascone.
AB  - The first total synthesis of monosporascone is presented. The five-step synthesis
      developed includes a silver acetylide-acid chloride coupling, domino Diels-Alder
      retro-Diels-Alder reaction, and an intramolecular Friedel-Crafts acylation, and
      provides the natural product in 57% yield overall. Selective reduction of
      monosporascone also afforded the related metabolite dihydromonosporascone. 

PMID- 24668448
TI  - An improved method and cost effective strategy for soluble expression and
      purification of human N-myristoyltransferase 1 in E. coli.
AB  - N-myristoyltransferase (NMT) is an indispensible enzyme, which exists as two
      isoforms (NMT1 and NMT2) in humans and has proven roles in development of
      cancerous states. It is thus a target for novel anti-cancer drug design, but
      understanding of the biochemical and functional differences of these isozymes is
      not fully deciphered. A soluble expression under the T7 promoter for human NMT1
      was achieved in E. coli BL21 (DE3) cells, devoid of any isopropyl beta-D-1
      thiogalactopyranoside-based induction. The identity of expressed protein was
      confirmed by matrix-assisted laser desorption ionization mass spectrometry
      peptide-fingerprint analysis and a two-step purification protocol yielded
      homogeneous enzyme. The intact mass of the purified protein was verified by
      electrospray ionization mass spectrometry and found to be in agreement with the
      theoretical mass (48.141 vs. 48.140 kDa). The fluorescence spectrophotometric
      analyses of the ligand binding and enzyme activity demonstrated that the
      recombinant form is functional. The yield of purified protein was ~8-10 mg/L
      culture (batch to batch variation) with a specific activity value of 18,500 +/-
      513 U/mg of protein under the experimental conditions used. The final
      verification of the myristoylation was demonstrated by mass spectrometry analysis
      of reaction product. The described approach could be readily adapted for
      production of human NMT1, with high yields of pure enzyme preparations, which
      should aid in downstream applications involving inhibitor design and structure
      function studies of NMT's. 

PMID- 24668449
TI  - Excitation of rat sympathetic neurons via M1 muscarinic receptors independently
      of Kv7 channels.
AB  - The slow cholinergic transmission in autonomic ganglia is known to be mediated by
      an inhibition of Kv7 channels via M1 muscarinic acetylcholine receptors. However,
      in the present experiments using primary cultures of rat superior cervical
      ganglion neurons, the extent of depolarisation caused by the M1 receptor agonist
      oxotremorine M did not correlate with the extent of Kv7 channel inhibition in the
      very same neuron. This observation triggered a search for additional mechanisms.
      As the activation of M1 receptors leads to a boost in protein kinase C (PKC)
      activity in sympathetic neurons, various PKC enzymes were inhibited by different
      means. Interference with classical PKC isoforms led to reductions in
      depolarisations and in noradrenaline release elicited by oxotremorine M, but left
      the Kv7 channel inhibition by the muscarinic agonist unchanged. M1 receptor
      induced depolarisations were also altered when extra- or intracellular Cl(-)
      concentrations were changed, as were depolarising responses to gamma-aminobutyric
      acid. Depolarisations and noradrenaline release triggered by oxotremorine M were
      reduced by the non-selective Cl(-) channel blockers 4-acetamido-4'-isothiocyanato
      stilbene-2,2'-disulfonic acid and niflumic acid. Oxotremorine M induced slowly
      rising inward currents at negative membrane potentials that were blocked by
      inhibitors of Ca(2+)-activated Cl(-) and TMEM16A channels and attenuated by PKC
      inhibitors. These channel blockers also reduced oxotremorine M-evoked
      noradrenaline release. Together, these results reveal that slow cholinergic
      excitation of sympathetic neurons involves the activation of classical PKCs and
      of Ca(2+)-activated Cl(-) channels in addition to the well-known inhibition of
      Kv7 channels.

PMID- 24668450
TI  - Molecular cloning and functional characterization of zebrafish Slc4a3/Ae3 anion
      exchanger.
AB  - The zebrafish genome encodes two slc4a1 genes, one expressed in erythroid tissues
      and the other in the HR (H(+)-ATPase-rich) type of embryonic skin ionocytes, and
      two slc4a2 genes, one in proximal pronephric duct and the other in several
      extrarenal tissues of the embryo. We now report cDNA cloning and functional
      characterization of zebrafish slc4a3/ae3 gene products. The single ae3 gene on
      chromosome 9 generates at least two low-abundance ae3 transcripts differing only
      in their 5'-untranslated regions and encoding a single definitive Ae3 polypeptide
      of 1170 amino acids. The 7 kb upstream of the apparent initiator Met in ae3 exon
      3 comprises multiple diverse, mobile repeat elements which disrupt and appear to
      truncate the Ae3 N-terminal amino acid sequence that would otherwise align with
      brain Ae3 of other species. Embryonic ae3 mRNA expression was detected by whole
      mount in situ hybridization only in fin buds at 24-72 hpf, but was detectable by
      RT-PCR across a range of embryonic and adult tissues. Epitope-tagged Ae3
      polypeptide was expressed at or near the surface of Xenopus oocytes, and mediated
      low rates of DIDS-sensitive (36)Cl(-)/Cl(-) exchange in influx and efflux assays.
      As previously reported for Ae2 polypeptides, (36)Cl(-) transport by Ae3 was
      inhibited by both extracellular and intracellular acidic pH, and stimulated by
      alkaline pH. However, zebrafish Ae3 differed from Ae2 polypeptides in its
      insensitivity to NH4Cl and to hypertonicity. We conclude that multiple repeat
      elements have disrupted the 5'-end of the zebrafish ae3 gene, associated with N
      terminal truncation of the protein and reduced anion transport activity.

PMID- 24668451
TI  - Combination of dynamic pH junction with capillary electrophoresis-mass
      spectrometry for the determination of systemins in plant samples.
AB  - Systemin is an important group of plant peptide hormones participating in the
      regulation of plant defensive responses. An improved method, based on dynamic pH
      junction and capillary electrophoresis-quadrupole time-of-flight mass
      spectrometry, was developed for online enrichment and sensitive determination of
      trace systemins in plants. After optimization, the online enrichment factors for
      six target systemins ranged from 90- to 127-fold. The detection limits reached
      lower than 0.5 nM, which were comparable with the sensitivity of LC-MS method.
      Satisfactory quantitative results were obtained in terms of linearity (R(2) >=
      0.993), dynamic range (3-120 ng/mL), and reproducibility (<=6.7%). For the
      analysis of real plant samples, a rapid sample preparation method was developed,
      using two steps of SPE purification with different retention and separation
      mechanisms. Finally, this method realized the successful detection of tomato
      systemin and tobacco hydroxyproline-rich systemin I from plant leaves with
      shorter analysis time.

PMID- 24668452
TI  - Laparoscopic versus open reversal of a Hartmann procedure: a single-center study.
AB  - PURPOSE: Re-anastomosis after a Hartmann procedure is associated with a higher
      morbidity and mortality than other elective colorectal operations. The goal of
      this comparative study was to evaluate whether laparoscopic reversal is a
      justified operative approach, although the initial operation is most often an
      emergency laparotomy. METHODS: A retrospective analysis was conducted on data
      collected on all 70 patients who underwent laparoscopic and open reversal of a
      Hartmann procedure at the Department of Surgery, University of Schleswig
      Holstein, Campus Lubeck, between January 1999 and December 2011. Together with
      general demographic data, the analysis included the indication for the initial
      Hartmann procedure, time to reversal, intraoperative findings, the choice of
      operative method, operating time, postoperative pain control, return of normal
      bowel function, length of hospital stay, and peri- and postoperative morbidity
      and mortality. RESULTS: In most patients, the Hartmann procedure was performed
      after a perforated sigmoid diverticulitis. We were not able to find any
      statistically significant differences with respect to gender, body mass index
      (BMI) and American Society of Anesthesiologists classification between the
      laparoscopic group (LG) (N = 24 patients) and the open group (OG) (N = 46). In
      the LG, patients were significantly younger (p = 0.019). The median operating
      time was 210 min (75-245) in the LG, which was significantly longer than in the
      OG (166 min; 66-230). The statistical analysis of the duration of postoperative
      analgesic therapy (LG 7 days; OG 12 days), return to normal diet (LG 3 days; OG 4
      days), return of normal bowel function (LG 3 days; OG 4 days) and length of
      hospital stay (LOS) (LG 10 days; OG 15 days) detected significant differences in
      advantage for the LG. Unplanned return to theatre during index admission was only
      necessary in the OG (N = 7, 15.2 %). With a median follow-up of 8 months (range 1
      20), we observed a comparable number of minor complications in both groups but a
      significantly higher number of major complications in the OG (N = 27, 58.7%) (p =
      0.001). Conversion occurred in three cases (12.5%). There was no mortality in
      either of the two groups. CONCLUSIONS: This study was able to demonstrate the
      feasibility of the laparoscopic approach. In terms of postoperative results it
      should be seen as equivalent to the open procedure. However, the laparoscopic
      approach requires profound surgical expertise. The indication should be made
      after a careful risk/benefit analysis for each individual patient.

PMID- 24668453
TI  - Postoperative ulnar neuropathy is not necessarily iatrogenic: a prospective study
      on dynamic ulnar nerve dislocation at the elbow.
AB  - BACKGROUND: Patients who undergo surgery may develop ulnar neuropathy. Although
      the mechanism of ulnar neuropathy is still not clear, ulnar neuropathies are
      common causes of successful lawsuits against surgeons. Recently, the concept
      developed that endogenous patient factors can lead to postoperative peripheral
      neuropathies. We hypothesize that dynamic ulnar nerve dislocation at the elbow
      (DUNDE) may be a predisposing factor for ulnar irritation (i.e., neuropathy) in
      normal subjects. METHODS: In a prospective investigation, patients aged 20 years
      and older presenting in our emergency department were asked to participate. Three
      physicians examined both elbows of subjects included in our study for evidence of
      DUNDE (through clinical and sonographic examination) and for clinical symptoms
      related to ulnar neuropathy. RESULTS: Dynamic ulnar nerve dislocation was
      observed in 29.3% of examined subjects. No significant difference in its
      occurrence was observed in relation to gender or dominant side. Physical
      examination with provocation tests demonstrated significantly more positive Tinel
      tests and spontaneous signs of neuropathy in patients with dynamic dislocating
      ulnar nerves (14.7 vs. 1.1%). CONCLUSION: Dynamic ulnar nerve dislocation may be
      linked to ulnar nerve irritability (i.e., ulnar neuropathy) in normal subjects
      without history of trauma, surgical procedure, or anesthesia. Considering the
      high incidence of this variant in the general population, our study supports
      previous investigations suggesting that many postoperative ulnar nerve deficits
      are traceable to chronic patient conditions. Our study suggests that dynamic
      ulnar nerve dislocation is a predisposing factor in the development of ulnar
      neuropathy in the postoperative period. NOTES: (1) neuropathy should be viewed as
      a broad definition as signs of nerve irritation/inflammation, and independently
      of the pathophysiology and etiology; (2) because no specific term exists in the
      international anatomic nomenclature (Nomina Anatomica) to designate this variant,
      several synonyms have been used in the literature, leading to confusion and
      misleading conclusions concerning its traumatic etiologies and their
      consequences: (a) recurrent or habitual ulnar nerve luxation (or subluxation);
      (b) recurrent or habitual ulnar nerve dislocation; (c) ulnar nerve instability;
      (d) laxity of the ulnar nerve; and (e) ulnar nerve hypermobility.

PMID- 24668454
TI  - Vitamin E deficiency begins within 6 months after gastrectomy for gastric cancer.
AB  - BACKGROUND: To clarify factors related to vitamin E malabsorption after gastric
      surgery, we evaluated serum vitamin E levels in patients who had undergone
      gastrectomy for gastric cancer. METHODS: We studied 39 patients (26 men, 13
      women; mean age, 61.7 years) who underwent gastrectomy for early gastric cancer.
      Surgical procedures included 24 subtotal gastrectomies and 15 total
      gastrectomies. We measured serum levels of vitamin E before and 3, 6, 9, and 12
      months after gastrectomy. A level of less than 0.75 mg/dl was defined as a low
      vitamin E level. RESULTS: Serum vitamin E levels decreased to less than 0.75
      mg/dl in 6 (15.4%) of the 39 patients within 6 months after gastrectomy and in 7
      (17.9%) of the 39 patients within 1 year after gastrectomy. The proportion of
      patients with a low serum vitamin E level was significantly higher in the total
      gastrectomy group (p = 0.002). A low vitamin E level was significantly associated
      with a low total cholesterol level. Total cholesterol levels in low vitamin E
      levels patients were lower than normal vitamin E levels patients. None of the
      patients with a low vitamin E level had neuropathy. CONCLUSIONS: The type of
      operation performed (total vs. subtotal gastrectomy) may be the major cause of
      vitamin E malabsorption after gastrectomy for gastric cancer. Vitamin E
      deficiency probably begins within 6 months after gastrectomy for gastric cancer.

PMID- 24668455
TI  - Enhanced recovery pathway for urgent colectomy.
AB  - BACKGROUND: Enhanced recovery protocols have been proven to decrease
      complications and hospital stay following elective colorectal surgery. However,
      these principles have not yet been reported for urgent surgery procedures. We
      aimed to assess our initial experience with urgent colectomies performed within
      an established enhanced recovery pathway. METHODS: In a prospective cohort study,
      all patients undergoing colonic resection between April 2012 and March 2013 were
      treated according to a standardized enhanced recovery protocol. Urgent surgeries
      were compared with the elective procedures with regards to baseline
      characteristics, compliance with enhanced recovery items, and clinical outcome.
      RESULTS: Patients (N = 28) requiring urgent colonic resection were included and
      compared with patients undergoing elective colectomy (N = 63). Overall compliance
      with the protocol was 57% for the urgent compared with 77% for the elective
      procedures (p = 0.006). The pre-operative compliance was 64 versus 96% (p <
      0.001), the intra-operative compliance was 77 versus 86% (p = 0.145), and the
      post-operative compliance was 49 versus 67% (p = 0.015), for the urgent and
      elective resections, respectively. Overall, 18 urgent patients (64%) and 32
      elective patients (51%) developed postoperative complications (p = 0.261). Median
      postoperative length of stay was 8 days in the urgent setting compared with 5
      days in the elective setting (p = 0.006). CONCLUSIONS: Many of the intra
      operative and post-operative enhanced recovery items can also be applied to
      urgent colectomy, entailing outcomes that approach the results achieved in the
      elective setting.

PMID- 24668456
TI  - Glottal gap as an early predictor for permanent laryngoplasty in unilateral vocal
      fold paralysis.
AB  - OBJECTIVES/HYPOTHESIS: To assess the possible predictive factors for permanent
      laryngoplasty (PL) in patients with acute unilateral vocal fold paralysis (UVFP),
      and to assess the effects of early vocal cord hyaluronic acid injection. STUDY
      DESIGN: Prospective cohort study. METHODS: Patients diagnosed with UVFP within
      the previous 6 months were enrolled. Initial and follow-up
      videolaryngostroboscopy, voice laboratory analysis, laryngeal electromyography,
      and Voice Outcome Survey were performed. RESULTS: Fifty newly diagnosed UVFP
      patients were recruited. Eight were excluded after 12 months of follow-up and
      data for 42 patients were analyzed. In patients treated conservatively, the
      glottal gap was measured on presentation. Normalized glottal gap area (NGGA) was
      the only predictor of PL (P = 0.036) according to multivariate logistic
      regression analysis. A cutoff value of 7.36 resulted in sensitivity of 85.7% and
      specificity of 80.0% for predicting future PL. The PL rate was significantly
      higher in patients with an initial NGGA > 7.36 compared with <= 7.36. (6/9 vs.
      1/13; chi(2) = 6.71; P = 0.010). Among patients with an initial NGGA > 7.36,
      those who accepted early hyaluronic acid injection had a significantly lower rate
      of PL (1/11 vs. 6/9; chi(2) = 7.21; P = 0.007) and better social and emotional
      role functioning at follow-up. CONCLUSIONS: The glottal gap on presentation is a
      robust early predictor of PL. Early, office-based hyaluronic acid intracordal
      injection can reduce the need for PL in patients with a large NGGA.

PMID- 24668457
TI  - Renal radionuclide imaging, an evergreen forty years old.
AB  - Urinary tract congenital abnormalities (UCA) and febrile infections (UTI) are,
      respectively, 2 of the commonest congenital and acquired health problems in
      childhood. In both, radionuclide imaging still represent a cornerstone of
      diagnostic imaging, although the involved techniques are more or less the same
      from the early '80 s. During the last 2 decades, published papers focused on a
      deep revision about the optimal use and usefulness of such imaging tools in
      affected children, with the aim of reducing invasiveness, radiation burden and
      costs without losing efficacy. This approach leads to different results. In UCA,
      no consensus for a diagnostic algorithm was up to now reached, whilst, about
      febrile UTIs, guidelines were published in 2007 by the UK's National Institute
      for Clinical Excellence (NICE) and by the European Society of Paediatric
      Radiology (ESPR), in 2011 by the American Academy of Paediatrics (AAP), and in
      2012 by the Italian Society of Paediatric Nephrology (SINP). Nevertheless, new
      data continuously arise and the scientific debate always revives. Every imaging
      tool now available has its own strengths and weaknesses, and so all published
      guidelines. All this body of knowledge must be critically analysed for obtaining
      a complete, up-to-date and flexible overview about these "always hot" topics. 

PMID- 24668459
TI  - Potent organometallic osmium compounds induce mitochondria-mediated apoptosis and
      S-phase cell cycle arrest in A549 non-small cell lung cancer cells.
AB  - The problems of acquired resistance associated with platinum drugs may be
      addressed by chemotherapeutics based on other transition metals as they offer the
      possibility of novel mechanisms of action. In this study, the cellular uptake and
      induction of apoptosis in A549 human non-small cell lung cancer cells of three
      promising osmium(II) arene complexes containing azopyridine ligands, [Os(eta(6)
      arene)(p-R-phenylazopyridine)X]PF6, where arene is p-cymene or biphenyl, R is OH
      or NMe2, and X is Cl or I, were investigated. These complexes showed time
      dependent (4-48 h) potent anticancer activity with highest potency after 24 h
      (IC50 values ranging from 0.1 to 3.6 MUM). Cellular uptake of the three compounds
      as quantified by ICP-MS, was independent of their logP values (hydrophobicity).
      Furthermore, maximum cell uptake was observed after 24 h, with evident cell
      efflux of the osmium after 48 and 72 h of exposure, which correlated with the
      corresponding IC50 values. The most active compound 2, [Os(eta(6)-p-cymene)(NMe2
      phenylazopyridine)I]PF6, was taken up by lung cancer cells predominately in a
      temperature-dependent manner indicating that energy-dependent mechanisms are
      important in the uptake of 2. Cell fractionation studies showed that all three
      compounds accumulated mainly in cellular membranes. Furthermore, compound 2
      induced apoptosis and caused accumulation in the S-phase of the cell cycle. In
      addition, 2 induced cytochrome c release and alterations in mitochondrial
      membrane potential even after short exposure times, indicating that mitochondrial
      apoptotic pathways are involved. This study represents the first steps towards
      understanding the mode of action of this promising class of new osmium-based
      chemotherapeutics.

PMID- 24668458
TI  - Scaling of the mean and variance of population dynamics under fluctuating
      regimes.
AB  - Theoretical ecologists have long sought to understand how the persistence of
      populations depends on the interactions between exogenous (biotic and abiotic)
      and endogenous (e.g., demographic and genetic) drivers of population dynamics.
      Recent work focuses on the autocorrelation structure of environmental
      perturbations and its effects on the persistence of populations. Accurate
      estimation of extinction times and especially determination of the mechanisms
      affecting extinction times is important for biodiversity conservation. Here we
      examine the interaction between environmental fluctuations and the scaling effect
      of the mean population size with its variance. We investigate how interactions
      between environmental and demographic stochasticity can affect the mean time to
      extinction, change optimal patch size dynamics, and how it can alter the often
      assumed linear relationship between the census size and the effective population
      size. The importance of the correlation between environmental and demographic
      variation depends on the relative importance of the two types of variation. We
      found the correlation to be important when the two types of variation were
      approximately equal; however, the importance of the correlation diminishes as one
      source of variation dominates. The implications of these findings are discussed
      from a conservation and eco-evolutionary point of view. 

PMID- 24668460
TI  - Capuchin monkey research priorities and urgent issues.
AB  - The "Capuchin research community roundtable: working together towards a
      comparative biology of Cebus and Sapajus" was held at the International
      Primatological Society Congress in Cancun, Mexico, August 2012. Goals of the
      roundtable were to strengthen interactions among the capuchin research community,
      and to prioritize and coordinate research and training in a more systematic and
      interactive way in light of increasing conservation urgency. New phylogenetic and
      biogeographic evidence highlights the distinct evolutionary histories of the two
      radiations of capuchin monkeys, Cebus (untufted or gracile capuchins) and Sapajus
      (tufted or robust capuchins), that were formerly lumped under Cebus, and points
      to a higher number of species, or Evolutionarily Significant Units, in each
      compared to past capuchin taxonomies. Many of the lesser-known species face
      increasing fragmentation and destruction of habitat, and most populations of
      still non-threatened species face encroachment from human settlements. Here, we
      present capuchin research priorities and urgent issues based on the discussion by
      capuchin researchers in the roundtable. These include a call for the immediate
      end to the use of the name Cebus apella and the employment of the term Sapajus
      spp. instead for captive robust capuchins of unknown origin; for the
      implementation of rapid assessments for previously unstudied capuchin species or
      populations in biomes of interest; for the development of standardized methods to
      allow for comparative analyses across capuchin field sites; and for the creation
      and maintenance of an open-access website for capuchin monkey data. Finally, we
      planned the creation of an international Capuchin Action Network, to help
      disseminate research information; to work as a research community in a more
      efficient, collaborative manner; to help prioritize research and conservation
      goals as a community of experts; and to strengthen our political voice.

PMID- 24668462
TI  - The crystal structure of fibroblast growth factor 18 (FGF18).

PMID- 24668463
TI  - Regiospecific coordination of Re(3) clusters with the sumanene-type hexagons on
      endohedral metallofullerenes and higher fullerenes that provides an efficient
      separation method.
AB  - The reactions of [(MU-H)3 Re3 (CO)11 (NCMe)] with Sc2 @C82 -C3v (8), Sc2 C2 @C80 
      C2v (5), Sc2 O@C82 -Cs (6), C86 -C2 (17), and C86 -Cs (16) have been carried out
      to produce face-capping cluster complexes. The Re3 triangles are found to bind to
      the sumanene-type hexagons on the fullerene surface regiospecifically. In
      contrast, Sc3 N@C78 -D3h (5) and Sc3 N@C80 -Ih show no reactivity toward [(MU-H)3
      Re3 (CO)11 (NCMe)], probably due to electronic and steric factors. These
      complexes can be easily purified by using HPLC. Carbonylation of each complex
      releases the corresponding higher fullerene or endohedral metallofullerene in
      pure form. Remarkably, the C86 -C2 (17) and C86 -Cs (16) isomers were
      successively separated through Re3 cluster complexation/decomplexation. This
      unique bonding feature may provide an attractive general strategy to purify as
      yet unresolved fullerene mixtures. 

PMID- 24668464
TI  - Treating inborn errors of liver metabolism with stem cells: current clinical
      development.
AB  - Advanced therapies including stem cells are currently a major biotechnological
      development. Adult liver stem cells can differentiate into hepatocyte like cells
      and be infused in the recipient's liver to bring a missing metabolic function.
      These cells can be produced in large quantities in vitro. Allogeneic stem cells
      are required to treat genetic diseases, and this approach allows to use one
      single source of tissue to treat different diseases and many recipients.
      Mesenchymal stem cells can in addition play an immunomodulatory and anti
      inflammatory role and possibly prevent the accumulation of fibrous tissue in the
      liver. From a regulatory point of view, stem cells are considered as medicinal
      products, and must undergo a pharmaceutical development that goes beyond the
      research and proof-of-concept phases. Here, we review the track followed from the
      first hepatocyte transplantation in 2000 to the next generation product issued
      from stem cell technology, and the start of EMA approved clinical trials to
      evaluate the safety and potency of liver stem cells for the treatment of inborn
      errors of the liver metabolism. 

PMID- 24668466
TI  - The penile clamp: medieval pain or makeshift gain?
AB  - INTRODUCTION AND OBJECTIVES: A significant number of men are affected by post
      prostatectomy urinary incontinence. If symptoms persist after conservative
      measures fail men are left with three choices: additional surgery, drainage or
      absorbent devices, or a penile compression device. Our center encountered a
      number of men for whom additional surgery was too dangerous and for whom drainage
      or absorbent devices were too cumbersome. Our objective was to investigate the
      level of symptomatic improvement and ease of utility of a penile compression
      device (DribblestopTM, Rennich Industries, Ltd., Calgary, Canada) in this
      population. PATIENTS AND METHODS: Patients who were prescribed the penile
      compression device across 10 New Zealand Centers were contacted to complete an
      Incontinence Impact Questionnaire (IIQ-7) regarding symptomatic improvement
      before and after the use of the compression device. The data were then analyzed
      for improvement scores pre and post intervention. RESULTS: Eighteen men were
      contacted across 10 New Zealand centers. There was an 89% response rate for
      interview. The average pre-intervention IIQ-7 score was 67.3 out of 100. The
      average post-intervention IIQ-7 score was 26.8 out of 100. The reduction in
      average symptomatic score was 40.5 (P < 0.05). The interviewees found the device
      easy to use, felt more confident wearing the device, and had increased levels of
      physical activity with device in situ. CONCLUSION: This study demonstrates that
      men who used the penile compression device reduced their Incontinence Impact
      Questionnaire scores significantly. Further research into the side effect profile
      of the device is needed as its utility may be under appreciated.

PMID- 24668465
TI  - Systematic review and meta-analysis of the effectiveness and safety of extended
      lymphadenectomy in patients with resectable gastric cancer.
AB  - BACKGROUND: The extent of lymphadenectomy in the treatment of gastric cancer has
      been debated for more than two decades. This meta-analysis sought to evaluate the
      effectiveness and safety of extended lymphadenectomy in patients with gastric
      cancer. METHODS: A comprehensive search was performed to identify randomized
      clinical trials (RCTs) comparing the outcomes of D1 and D2 dissection for gastric
      cancer in PubMed, EMBASE, the Cochrane Library, Science Citation Index, Web of
      Science and the Chinese Biomedical Literature Database in any language from
      inception of the database to March 2012. Meta-analyses were performed using
      Review Manager software. RESULTS: Eight RCTs including a total of 2044 patients
      (D1, 1042; D2, 1002) were eligible for meta-analysis. Five-year survival and
      haemorrhage rates were similar in the two groups. There were significant
      differences in morbidity, anastomotic leakage, pancreatic leakage, reoperation
      rates, wound infection, pulmonary complications and postoperative mortality, all
      of which favoured D1 dissection. Subgroup analysis indicated a trend towards
      lower gastric cancer-related mortality in patients undergoing D2 dissection who
      did not also have resection of the spleen or pancreas. CONCLUSION: D2 dissection
      was associated with a significantly higher postoperative risk. A trend towards
      lower gastric cancer-related mortality was found following D2 dissection that did
      not include resection of the spleen or pancreas, but further long-term survival
      data are needed to determine whether there is a specific survival benefit after
      D2 dissection.

PMID- 24668467
TI  - NGF, BDNF, NT3, and NT4.
AB  - The discovery of nerve growth factor (NGF) was a seminal event in history of
      research in developmental neurobiology. The further discovery that NGF was just
      one of a family of structurally similar growth factors, neurotrophins, provided
      important insights into the way nerve cells communicate, during development of
      the nervous system, and in neuroplasticity, memory, and learning in the adult
      nervous system. Four neurotrophins, NGF, brain-derived neurotrophic factor
      (BDNF), neurotrophin-3 (NT3), and neurotrophin-4 (NT4), regulate a wide variety
      of neural functions, acting upon p75NTR, TrkA, TrkB, and TrkC receptors. 

PMID- 24668468
TI  - Deciphering proneurotrophin actions.
AB  - Like most growth factors, neurotrophins are initially synthesized as precursors
      that are cleaved to release C-terminal mature forms. The well-characterized
      mature neurotrophins bind to Trk receptors to initiate survival and
      differentiative responses. More recently, the precursor forms or proneurotrophins
      have been found to act as distinct ligands by binding to an unrelated receptor
      complex consisting of the p75 neurotrophin receptor (p75) and sortilin to
      initiate cell death. Induction of proNGF and p75 has been observed in preclinical
      injury models and in pathological states in the central nervous system, and
      strategies that block the proNGF/p75 interaction are effective in limiting
      neuronal apoptosis. In contrast, the mechanisms that regulate expression of other
      proneurotrophins, including proBDNF and proNT-3, are less well understood. Here,
      recent findings on the biological actions, regulation of expression, and
      pathophysiological effects of proneurotrophins will be reviewed. 

PMID- 24668469
TI  - Spatiotemporal intracellular dynamics of neurotrophin and its receptors.
      Implications for neurotrophin signaling and neuronal function.
AB  - Neurons possess a polarized morphology specialized to contribute to neuronal
      networks, and this morphology imposes an important challenge for neuronal
      signaling and communication. The physiology of the network is regulated by
      neurotrophic factors that are secreted in an activity-dependent manner modulating
      neuronal connectivity. Neurotrophins are a well-known family of neurotrophic
      factors that, together with their cognate receptors, the Trks and the p75
      neurotrophin receptor, regulate neuronal plasticity and survival and determine
      the neuronal phenotype in healthy and regenerating neurons. Is it now becoming
      clear that neurotrophin signaling and vesicular transport are coordinated to
      modify neuronal function because disturbances of vesicular transport mechanisms
      lead to disturbed neurotrophin signaling and to diseases of the nervous system.
      This chapter summarizes our current understanding of how the regulated secretion
      of neurotrophin, the distribution of neurotrophin receptors in different
      locations of neurons, and the intracellular transport of neurotrophin-induced
      signaling in distal processes are achieved to allow coordinated neurotrophin
      signaling in the cell body and axons. 

PMID- 24668470
TI  - Neurotrophins: transcription and translation.
AB  - Neurotrophins are powerful molecules. Small quantities of these secreted proteins
      exert robust effects on neuronal survival, synapse stabilization, and synaptic
      function. Key functions of the neurotrophins rely on these proteins being
      expressed at the right time and in the right place. This is especially true for
      BDNF, stimulus-inducible expression of which serves as an essential step in the
      transduction of a broad variety of extracellular stimuli into neuronal plasticity
      of physiologically relevant brain regions. Here we review the transcriptional and
      translational mechanisms that control neurotrophin expression with a particular
      focus on the activity-dependent regulation of BDNF. 

PMID- 24668471
TI  - Trk receptors.
AB  - The tropomyosin-related tyrosine kinase (Trk) receptors were initially described
      as a family of growth factor receptors required for neuronal survival. They have
      since been shown to influence many aspects of neuronal development and function,
      including differentiation, outgrowth, and synaptic plasticity. This chapter will
      give an overview on the biology of Trk receptors within the nervous system. The
      structure and downstream signaling pathways of the full-length receptors will be
      described, as well as the biological functions of their truncated isoforms.
      Finally, the role of Trk receptors in the nervous system in health and disease
      will be discussed. 

PMID- 24668472
TI  - The biological functions and signaling mechanisms of the p75 neurotrophin
      receptor.
AB  - The p75 neurotrophin receptor (p75(NTR)) regulates a wide range of cellular
      functions, including programmed cell death, axonal growth and degeneration, cell
      proliferation, myelination, and synaptic plasticity. The multiplicity of cellular
      functions governed by the receptor arises from the variety of ligands and co
      receptors which associate with p75(NTR) and regulate its signaling. P75(NTR)
      promotes survival through interactions with Trk receptors, inhibits axonal
      regeneration via partnerships with Nogo receptor (Nogo-R) and Lingo-1, and
      promotes apoptosis through association with Sortilin. Signals downstream of these
      interactions are further modulated through regulated intramembrane proteolysis
      (RIP) of p75(NTR) and by interactions with numerous cytosolic partners. In this
      chapter, we discuss the intricate signaling mechanisms of p75(NTR), emphasizing
      how these signals are differentially regulated to mediate these diverse cellular
      functions. 

PMID- 24668473
TI  - Sortilins in neurotrophic factor signaling.
AB  - The sortilin family of Vps10p-domain receptors includes sortilin, SorLA, and
      SorCS1-3. These type-I transmembrane receptors predominate in distinct neuronal
      tissues, but expression is also present in certain specialized non-neuronal cell
      populations including hepatocytes and cells of the immune system. The biology of
      sortilins is complex as they participate in both cell signaling and in
      intracellular protein sorting. Sortilins function physiologically in signaling by
      pro- and mature neurotrophins in neuronal viability and functionality. Recent
      genome-wide association studies have linked members to neurological disorders
      such as Alzheimer's disease and bipolar disorder and outside the nervous system
      to development of coronary artery disease and type-2 diabetes. Particularly well
      described are the receptor functions in neuronal signaling by pro- (proNT) and
      mature (NT) neurotrophins and in the processing/metabolism of amyloid precursor
      protein (APP). 

PMID- 24668474
TI  - Neurotrophins in the regulation of cellular survival and death.
AB  - The neurotrophins play crucial roles regulating survival and apoptosis in the
      developing and injured nervous system. The four neurotrophins exert profound and
      crucial survival effects on developing peripheral neurons, and their expression
      and action is intimately tied to successful innervation of peripheral targets. In
      the central nervous system, they are dispensable for neuronal survival during
      development but support neuronal survival after lesion or other forms of injury.
      Neurotrophins also regulate apoptosis of both peripheral and central neurons, and
      we now recognize that there are regulatory advantages to having the same
      molecules regulate life and death decisions. This chapter examines the biological
      contexts in which these events take place and highlights the specific ligands,
      receptors, and signaling mechanisms that allow them to occur. 

PMID- 24668475
TI  - BDNF and synaptic plasticity, cognitive function, and dysfunction.
AB  - Among all neurotrophins, brain-derived neurotrophic factor (BDNF) stands out for
      its high level of expression in the brain and its potent effects on synapses. It
      is now widely accepted that the main function of BDNF in the adult brain is to
      regulate synapses, with structural and functional effects ranging from short-term
      to long-lasting, on excitatory or inhibitory synapses, in many brain regions. The
      diverse effects of BDNF on brain synapses stem from its complex downstream
      signaling cascades, as well as the diametrically opposing effects of the pro- and
      mature form through distinct receptors, TrkB and p75(NTR). Many aspects of BDNF
      cell biology are regulated by neuronal activity. The synergistic interactions
      between neuronal activity and synaptic plasticity by BDNF make it an ideal and
      essential regulator of cellular processes that underlie cognition and other
      complex behaviors. Indeed, numerous studies firmly established that BDNF plays a
      critical role in hippocampal long-term potentiation (LTP), a long-term
      enhancement of synaptic efficacy thought to underlie learning and memory.
      Converging evidence now strongly suggest that deficits in BDNF signaling
      contribute to the pathogenesis of several major diseases and disorders such as
      Huntington's disease, Alzheimer's disease, and depression. Thus, manipulating
      BDNF pathways represents a viable treatment approach to a variety of neurological
      and psychiatric disorders. 

PMID- 24668476
TI  - Nerve growth factor and nociception: from experimental embryology to new
      analgesic therapy.
AB  - Nerve growth factor (NGF) is central to the development and functional regulation
      of sensory neurons that signal the first events that lead to pain. These sensory
      neurons, called nociceptors, require NGF in the early embryo to survive and also
      for their functional maturation. The long road from the discovery of NGF and its
      roles during development to the realization that NGF plays a major role in the
      pathophysiology of inflammatory pain will be reviewed. In particular, we will
      discuss the various signaling events initiated by NGF that lead to long-lasting
      thermal and mechanical hyperalgesia in animals and in man. It has been realized
      relatively recently that humanized function blocking antibodies directed against
      NGF show remarkably analgesic potency in human clinical trials for painful
      conditions as varied as osteoarthritis, lower back pain, and interstitial
      cystitis. Thus, anti-NGF medication has the potential to make a major impact on
      day-to-day chronic pain treatment in the near future. It is therefore all the
      more important to understand the precise pathways and mechanisms that are
      controlled by NGF to both initiate and sustain mechanical and thermal
      hyperalgesia. Recent work suggests that NGF-dependent regulation of the
      mechanosensory properties of sensory neurons that signal mechanical pain may open
      new mechanistic avenues to refine and exploit relevant molecular targets for
      novel analgesics. 

PMID- 24668477
TI  - Neurotrophins and the regulation of energy balance and body weight.
AB  - Complex interactions between the brain and peripheral tissues mediate the
      effective control of energy balance and body weight. Hypothalamic and hindbrain
      neural circuits integrate peripheral signals informing the nutritional status of
      the animal and in response regulate nutrient intake and energy utilization.
      Obesity and its many medical complications emerge from the dysregulation of
      energy homeostasis. Excessive weight gain might also arise from alterations in
      reward systems of the brain that drive consumption of calorie dense, palatable
      foods in the absence of an energy requirement. Several neurotrophins, most
      notably brain-derived neurotrophic factor, have been implicated in the molecular
      and cellular processes underlying body weight regulation. Here, we review
      investigations interrogating their roles in energy balance and reward centers of
      the brain impacting feeding behavior and energy expenditure. 

PMID- 24668478
TI  - The biology of neurotrophins: cardiovascular function.
AB  - This chapter addresses the role of neurotrophins in the development of the heart,
      blood vessels, and neural circuits that control cardiovascular function, as well
      as the role of neurotrophins in the mature cardiovascular system. The
      cardiovascular system includes the heart and vasculature whose functions are
      tightly controlled by the nervous system. Neurons, cardiomyocytes, endothelial
      cells, vascular smooth muscle cells, and pericytes are all targets for
      neurotrophin action during development. Neurotrophin expression continues
      throughout life, and several common pathologies that impact cardiovascular
      function involve changes in the expression or activity of neurotrophins. These
      include atherosclerosis, hypertension, diabetes, acute myocardial infarction, and
      heart failure. In many of these conditions, altered expression of neurotrophins
      and/or neurotrophin receptors has direct effects on vascular endothelial and
      smooth muscle cells in addition to effects on nerves that modulate vascular
      resistance and cardiac function. This chapter summarizes the effects of
      neurotrophins in cardiovascular physiology and pathophysiology. 

PMID- 24668479
TI  - Neurotrophin signalling and transcription programmes interactions in the
      development of somatosensory neurons.
AB  - Somatosensory neurons of the dorsal root ganglia are generated from multipotent
      neural crest cells by a process of progressive specification and differentiation.
      Intrinsic transcription programmes active in somatosensory neuron progenitors and
      early post-mitotic neurons drive the cell-type expression of neurotrophin
      receptors. In turn, signalling by members of the neurotrophin family controls
      expression of transcription factors that regulate neuronal sub-type
      specification. This chapter explores the mechanisms by which this crosstalk
      between neurotrophin signalling and transcription programmes generates the
      diverse functional sub-types of somatosensory neurons found in the mature animal.

PMID- 24668480
TI  - Huntington's disease.
AB  - Changes in the level and activity of brain-derived neurotrophic factor (BDNF)
      have been described in a number of neurodegenerative disorders since early 1990s.
      However, only in Huntington disease (HD) gain- and loss-of-function experiments
      have mechanistically linked these abnormalities with the genetic defect.In this
      chapter we will describe how huntingtin protein, whose mutation causes HD, is
      involved in the physiological control of BDNF synthesis and transport in neurons
      and how both processes are simultaneously disrupted in HD. We will describe the
      underlying molecular mechanisms and discuss pre-clinical data concerning the
      impact of the experimental manipulation of BDNF levels on HD progression. These
      studies have revealed that a major loss of BDNF protein in the brain of HD
      patients may contribute to the clinical manifestations of the disease. The
      experimental strategies under investigation to increase brain BDNF levels in
      animal models of HD will also be described, with a view to ultimately improving
      the clinical treatment of this condition. 

PMID- 24668481
TI  - Motoneuron disease.
AB  - Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) represent
      the two major forms of motoneuron disease. In both forms of disease, spinal and
      bulbar motoneurons become dysfunctional and degenerate. In ALS, cortical
      motoneurons are also affected, which contributes to the clinical phenotype. The
      gene defects for most familial forms of ALS and SMA have been discovered and they
      point to a broad spectrum of disease mechanisms, including defects in RNA
      processing, pathological protein aggregation, altered apoptotic signaling, and
      disturbed energy metabolism. Despite the fact that lack of neurotrophic factors
      or their corresponding receptors are not found as genetic cause of motoneuron
      disease, signaling pathways initiated by neurotrophic factors for motoneuron
      survival, axon growth, presynaptic development, and synaptic function are
      disturbed in ALS and SMA. Better understanding of how neurotrophic factors and
      downstream signaling pathways interfere with these disease mechanisms could help
      to develop new therapies for motoneuron disease and other neurodegenerative
      disorders. 

PMID- 24668482
TI  - Neurotrophic factors in spinal cord injury.
AB  - A major challenge in repairing the injured spinal cord is to assure survival of
      damaged cells and to encourage regrowth of severed axons. Because neurotrophins
      are known to affect these processes during development, many experimental
      approaches to improving function of the injured spinal cord have made use of
      these agents, particularly Brain derived neurotrophic factor (BDNF) and
      Neurotrophin-3 (NT-3). More recently, neurotrophins have also been shown to
      affect the physiology of cells and synapses in the spinal cord. The effect of
      neurotrophins on circuit performance adds an important dimension to their
      consideration as agents for repairing the injured spinal cord. In this chapter we
      discuss the role of neurotrophins in promoting recovery after spinal cord injury
      from both a structural and functional perspective. 

PMID- 24668483
TI  - Neurotrophins and psychiatric disorders.
AB  - Increasing number of studies has during the last decade linked neurotrophic
      factors with the pathophysiology of neuropsychiatric disorders and with the
      mechanisms of action of drugs used for the treatment of these disorders. In
      particular, brain-derived neurotrophic factor BDNF and its receptor TrkB have
      been connected with the pathophysiology in mood disorders, and there is strong
      evidence that BDNF signaling is critically involved in the recovery from
      depression with both pharmacological and psychological means. Neurotrophins play
      a central role in neuronal plasticity and network connectivity in developing
      adult brain, and recent evidence links plasticity and network rewiring with mood
      disorders and their treatment. Therefore, neurotrophins should not be seen as
      happiness factors but as critical tools in the process where brain networks are
      optimally tuned to environment, and it is against this background that the
      effects of neurotrophins on neuropsychiatric disorders should be looked at. 

PMID- 24668484
TI  - Brain-derived neurotrophic factor and Rett syndrome.
AB  - Rett syndrome (RTT) is a devastating neurodevelopmental disorder with autistic
      features caused by loss-of-function mutations in the gene encoding methyl-CpG
      binding protein 2 (MECP2), a transcriptional regulatory protein. RTT has
      attracted widespread attention not only because of the urgent need for
      treatments, but also because it has become a window into basic mechanisms
      underlying epigenetic regulation of neuronal genes, including BDNF. In addition,
      work in mouse models of the disease has demonstrated the possibility of symptom
      reversal upon restoration of normal gene function. This latter finding has
      resulted in a paradigm shift in RTT research and, indeed, in the field of
      neurodevelopmental disorders as a whole, and spurred the search for potential
      therapies for RTT and related syndromes. In this context, the discovery that
      expression of BDNF is dysregulated in RTT and mouse models of the disease has
      taken on particular importance. This chapter reviews the still evolving story of
      how MeCP2 might regulate expression of BDNF, the functional consequences of BDNF
      deficits in Mecp2 mutant mice, and progress in developing BDNF-targeted therapies
      for the treatment of RTT. 

PMID- 24668485
TI  - Modulation of neurotrophin signaling by monoclonal antibodies.
AB  - The neurotrophin family is comprised of the structurally related secreted
      proteins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF),
      neurotrophin-3 (NT-3), and neurotrophine-4 (NT-4). They bind and activate the
      tyrosine kinase receptors Trk A, B, and C in a ligand-specific manner and
      additionally bind a shared p75NTR receptor. The neurotrophins were originally
      defined by their ability to support the survival and maturation of embryonic
      neurons. However, they also control important physiological functions of the
      adult nervous system including learning and memory, sensation, and energy
      homeostasis. For example, NGF/trkA signaling is critical for normal and
      pathological sensation of pain. Likewise, the BDNF/trkB pathway controls feeding
      and metabolism, and its dysfunction leads to severe obesity. Antibodies can
      modulate neurotrophin signaling. Thus, NGF blocking agents can attenuate pain in
      several animal models, and a recombinant humanized NGF blocking antibody
      (Tanezumab) has shown promising results in human clinical trials for
      osteoarthritic pain. On the other hand trkB agonist antibodies can modulate food
      intake and body weight in rodents and nonhuman primates. The power of monoclonal
      antibodies to modulate neurotrophin signaling promises to turn the rich
      biological insights into novel human medicines. 

PMID- 24668486
TI  - Assessment of the orbital-optimized coupled-electron pair theory for
      thermochemistry and kinetics: improving on CCSD and CEPA(1).
AB  - An assessment of the orbital-optimized coupled-electron pair theory [or simply
      "optimized CEPA(0)," OCEPA(0)] [Bozkaya and Sherrill, J. Chem. Phys. 2013, 139,
      054104] for thermochemistry and kinetics is presented. The OCEPA(0) method is
      applied to closed- and open-shell reaction energies, barrier heights, and radical
      stabilization energies (RSEs). The performance of OCEPA(0) is compared with those
      of the MP2, CEPA(0), OCEPA(0), CEPA(1), coupled-cluster singles and doubles
      (CCSD), and CCSD(T) methods [at complete basis set limits employing cc-pVTZ and
      cc-pVQZ basis sets]. For the most of the test sets, the OCEPA(0) method performs
      better than CEPA(0), CEPA(1), and CCSD, and provides accurate results.
      Especially, for open-shell reaction energies and barrier heights, the OCEPA(0)
      CEPA(1) and OCEPA(0)-CCSD differences become obvious. Similarly, for barrier
      heights and RSEs, the OCEPA(0) method improves on CEPA(0) by 1.6 and 2.3 kcal
      mol(-1) . Our results demonstrate that the CEPA(0) method dramatically fails when
      the reference wave function suffers from the spin-contamination problem.
      Conversely, the OCEPA(0) method can annihilate spin-contamination in the
      unrestricted-Hartree-Fock initial guess orbitals and can yield stable solutions.
      For overall evaluation, we conclude that the OCEPA(0) method is quite helpful not
      only for problematic open-shell systems and transition-states but also for closed
      shell molecules. Hence, one may prefer OCEPA(0) over CEPA(0), CEPA(1), and CCSD
      as an O(N6) method, where N is the number of basis functions, for thermochemistry
      and kinetics. As discussed previously, the cost of the OCEPA(0) method is as much
      as of CCSD and CEPA(1) for energy computations. However, for analytic gradient
      computations, the OCEPA(0) method is two times less expensive than CCSD and
      CEPA(1). Further, the stationary properties of the OCEPA(0) method making it
      promising for excited state properties via linear response theory.

PMID- 24668487
TI  - Genetic diversity and association mapping of seed vigor in rice (Oryza sativa
      L.).
AB  - Seed vigor is closely related to direct seeding in rice (Oryza sativa L.).
      Previous quantitative trait locus (QTL) studies for seed vigor were mainly
      derived from bi-parental segregating populations and no report from natural
      populations. In this study, association mapping for seed vigor was performed on a
      selected sample of 540 rice cultivars (419 from China and 121 from Vietnam).
      Population structure was estimated on the basis of 262 simple sequence repeat
      (SSR) markers. Seed vigor was evaluated by root length (RL), shoot length (SL)
      and shoot dry weight in 2011 and 2012. Abundant phenotypic and genetic
      diversities were found in the studied population. The population was divided into
      seven subpopulations, and the levels of linkage disequilibrium (LD) ranged from
      10 to 80 cM. We identified 27 marker-trait associations involving 18 SSR markers
      for three traits. According to phenotypic effects for alleles of the detected
      QTLs, elite alleles were mined. These elite alleles could be used to design
      parental combinations and the expected results would be obtained by pyramiding or
      substituting the elite alleles per QTL (apart from possible epistatic effects).
      Our results demonstrate that association mapping can complement and enhance
      previous QTL information for marker-assisted selection and breeding by design.

PMID- 24668488
TI  - Synthesis and biological activity of novel bis-indole inhibitors of bacterial
      transcription initiation complex formation.
AB  - The increasing resistance of bacteria against clinically approved antibiotics is
      resulting in an alarming decrease in therapeutic options for today's clinicians.
      We have targeted the essential interaction between bacterial RNA polymerase and
      sigma(70)/sigma(A) for the development of lead molecules exhibiting a novel
      mechanism of antibacterial activity. Several classes of structurally related bis
      indole inhibitors of bacterial transcription initiation complex formation were
      synthesized and their antimicrobial activities were evaluated. Condensation of
      indole-7- and indole-2-carbohydrazides with 7- and 2-trichloroacetylindoles or
      indole-7- and indole-2-glyoxyloyl chlorides resulted in the successful synthesis
      of 7,7'-, 2,2'-, 2,7'- and 3,2'-linked bis-indole derivatives with -CO-NH-NH-CO-
      and -CO-CO-NH-NH-CO- linkers. Indole-7-glyoxyloyl chlorides were reacted with
      hydrazine hydrate in different ratios to afford respective -CO-CO-NH-NH-CO-CO-
      bis-indole or hydrazide derivatives. The resulting compounds were found to be
      active against the beta'-CH-sigma(70)/sigma interaction in ELISA assays and
      inhibited the growth of both Gram-positive and Gram-negative bacteria. Structure
      activity relationship (SAR) studies were performed in order to identify the
      structural features of the synthesized inhibitors required for biological
      activity. 

PMID- 24668489
TI  - Testing for designer stimulants: metabolic profiles of 16 synthetic cathinones
      excreted free in human urine.
AB  - The study of 34,561 urine specimens, submitted for designer stimulant testing
      between February 2011 and January 2013, provided an opportunity: to estimate the
      range of synthetic cathinones (SC) abused in the USA, to observe multiple
      examples of metabolic profiles for each drug in various stages of excretion in
      human urine, to evaluate the extent of metabolism of specific SC and to select
      metabolites or parent drugs for routine testing. Sixteen SC were found in random
      patient samples: buphedrone; butylone; 3,4-dimethylmethcathinone; ethcathinone; N
      ethylbuphedrone; ethylone; flephedrone; mephedrone; 4-methylbuphedrone; 3,4
      methylenedioxypyrovalerone (MDPV); 4-methyl-N-ethylcathinone; methylone;
      pentedrone; pentylone; alpha-pyrrolidinobutiophenone (PBP) and alpha
      pyrrolidinopentiophenone (PVP). After liquid/liquid extraction and
      trifluoroacetylation, specimens were screened by gas chromatography-mass
      spectrometry (GC-MS) for drugs and metabolites excreted free in urine. Each SC
      exhibited a characteristic metabolic profile, as shown by multiple examples.
      Metabolites' structures were postulated on the basis of their mass spectra. A
      large group of SC appears to metabolize extensively by carbonyl reduction into
      respective substituted ephedrines and further by N-dealkylation into
      norephedrines. Abundant metabolites in this group are essential markers of the
      parent drug use. Unchanged drugs are far less abundant or not found at all. SC
      with methylenedioxy attachment to the aromatic ring, metabolize by carbonyl
      reduction to a much lesser extent and are best detected as such in free urine
      fraction. PBP and PVP can be detected either unchanged or as metabolites,
      resulting from pyrrolidine ring degradation into primary amine followed by
      carbonyl reduction. MDPV appears in urine as such with no apparent free
      metabolites. 

PMID- 24668490
TI  - Quantitation of diethylene glycol and its metabolites by gas chromatography mass
      spectrometry or ion chromatography mass spectrometry in rat and human biological
      samples.
AB  - The misuse of the commonly used chemical diethylene glycol (DEG) has lead to many
      poisonings worldwide. Methods were developed for analysis of DEG and its
      potential metabolites; ethylene glycol, glycolic acid, oxalic acid, diglycolic
      acid and hydroxyethoxy acetic acid in human urine, serum and cerebrospinal fluid
      samples, collected following a DEG-associated poisoning in the Republic of Panama
      during 2006. In addition, methods were developed for rat blood, urine, kidney and
      liver tissue to support toxicokinetic analysis during the conduct of DEG acute
      toxicity studies in the rat. Sample analysis was conducted using two techniques;
      ion chromatography with suppressed conductivity and negative ion electrospray
      ionization with MS detection or with gas chromatography using electron impact
      ionization or methane negative chemical ionization with MS detection. Stable
      isotope-labeled analogs of each analyte were employed as quantitative internal
      standards in the assays. 

PMID- 24668491
TI  - Lymphomatoid papulosis as a harbinger of chronic lymphocytic leukemia.

PMID- 24668492
TI  - Role of altered growth factor receptor-mediated JAK2 signaling in growth and
      maintenance of human acute myeloid leukemia stem cells.
AB  - Acute myeloid leukemia (AML) is sustained by small populations of leukemia stem
      cells (LSCs) that can resist available treatments and represent important
      barriers to cure. Although previous studies have shown increased signal
      transducer and activator of transcription (STAT)3 and STAT5 phosphorylation in
      AML leukemic blasts, the role of Janus kinase (JAK) signaling in primary AML
      compared with normal stem cells has not been directly evaluated. We show here
      that JAK/STAT signaling is increased in LSCs, particularly from high-risk AML.
      JAK2 inhibition using small molecule inhibitors or interference RNA reduced
      growth of AML LSCs while sparing normal stem cells both in vitro and in vivo.
      Increased JAK/STAT activity was associated with increased expression and altered
      signaling through growth factor receptors in AML LSCs, including receptor
      tyrosine kinase c-KIT and FMS-related tyrosine kinase 3 (FLT3). Inhibition of c
      KIT and FLT3 expression significantly inhibited JAK/STAT signaling in AML LSCs,
      and JAK inhibitors effectively inhibited FLT3-mutated AML LSCs. Our results
      indicate that JAK/STAT signaling represents an important signaling mechanism
      supporting AML LSC growth and survival. These studies support continued
      evaluation of strategies for JAK/STAT inhibition for therapeutic targeting of AML
      LSCs. 

PMID- 24668493
TI  - Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS
      and AML using combined gene expression and DNA-methylation profiling.
AB  - Mutations in splice factor (SF) genes occur more frequently in myelodysplastic
      syndromes (MDS) than in acute myeloid leukemias (AML). We sequenced complementary
      DNA from bone marrow of 47 refractory anemia with excess blasts (RAEB) patients,
      29 AML cases with low marrow blast cell count, and 325 other AML patients and
      determined the presence of SF-hotspot mutations in SF3B1, U2AF35, and SRSF2. SF
      mutations were found in 10 RAEB, 12 AML cases with low marrow blast cell count,
      and 25 other AML cases. Our study provides evidence that SF-mutant RAEB and SF
      mutant AML are clinically, cytologically, and molecularly highly similar. An
      integrated analysis of genomewide messenger RNA (mRNA) expression profiling and
      DNA-methylation profiling data revealed 2 unique patient clusters highly enriched
      for SF-mutant RAEB/AML. The combined genomewide mRNA expression profiling/DNA
      methylation profiling signatures revealed 1 SF-mutant patient cluster with an
      erythroid signature. The other SF-mutant patient cluster was enriched for
      NRAS/KRAS mutations and showed an inferior survival. We conclude that SF-mutant
      RAEB/AML constitutes a related disorder overriding the artificial separation
      between AML and MDS, and that SF-mutant RAEB/AML is composed of 2 molecularly and
      clinically distinct subgroups. We conclude that SF-mutant disorders should be
      considered as myeloid malignancies that transcend the boundaries of AML and MDS. 

PMID- 24668494
TI  - Kink energy and kink dipole moments on vicinal Au(001) in halide electrolytes.
AB  - Using electrochemical scanning tunnelling microscopy, we measured the potential
      dependent kink energy and the corresponding dipole moments of kinks at step edges
      on vicinal Au(001) surfaces in chloride and bromide containing electrolytes.
      Combining the results of the potential dependence of the kink energy with
      impedance spectroscopy data for the surface charge, we can directly deduce the
      dipole moment of kinks at the Au steps with co-adsorbed Cl(-) and Br(-),
      respectively. We find MU(Cl) = (6.0 +/- 0.7) * 10(-3) eA and MU(Br) = (10.1 +/-
      0.6) * 10(-3) eA. 

PMID- 24668495
TI  - [Airway devices in the intensive care unit].
AB  - This review presents the potential indications for different airway devices in
      the intensive care unit (ICU). Since the interface during noninvasive ventilation
      is located outside the body, sedation is not regularly needed. Therefore,
      selection of a fitting mask is essential to avoid mask intolerance which is one
      of the biggest problems during noninvasive ventilation. Full-face masks are the
      interfaces mostly used for noninvasive ventilation to treat acute respiratory
      failure; here, mouth breathing is possible which is often necessary during acute
      respiratory failure. Good alternatives are total face masks and the helmet,
      whereas nasal masks and mouthpieces are not regularly used on the ICU.
      Extraglottic airway devices and coniotomy are used for the management of
      difficult airway situations on the ICU. Endotracheal intubation remains the gold
      standard procedure for airway management. However, this procedure is associated
      with a number of complications. Tracheostomy is the airway access of choice when
      long-term mechanical ventilation is necessary. 

PMID- 24668496
TI  - Pharmacokinetics and safety of human recombinant hepatocyte growth factor
      administered to vocal folds.
AB  - OBJECTIVES/HYPOTHESIS: Previous animal studies demonstrated that hepatocyte
      growth factor (HGF) has the potential to regenerate scarred vocal folds. In
      addition, HGF is now produced under a good manufacturing practice (GMP)
      procedure. Therefore, human clinical trials of HGF are warranted in patients with
      vocal fold scarring. In the current study, we investigated the pharmacokinetics
      and the local tissue responses of HGF administered to rat vocal folds. STUDY
      DESIGN: Prospective animal experiment. METHODS: Five MUg of recombinant human HGF
      was administered to the vocal folds of Sprague-Dawley rats (n = 60) using a
      microsyringe. The concentration of HGF in larynges and blood was investigated by
      enzyme-linked immunosorbent assay. To evaluate the local tissue responses caused
      by HGF administration, endoscopic and histological examinations were performed.
      RESULTS: HGF concentration in the larynges was 50.1 MUg/g tissue 5 minutes after
      administration. The concentration decreased rapidly to 1.71 MUg/g tissue at 12
      hours after administration and to 0.29 ng/g tissue at 24 hours after
      administration. Seven days after administration, HGF concentration was minimal in
      one-half of the cases and was not detected in the other cases. Transmission of
      HGF to blood was detected in two of six cases at 5 minutes after administration,
      but was no longer detected 12 hours later. Endoscopic and histological
      examinations revealed no edema or erythema of the vocal folds in any of the
      cases. CONCLUSIONS: The current results contribute to the safety and
      pharmacokinetic management of future clinical trials using HGF administered to
      vocal folds.

PMID- 24668497
TI  - The earlier the better: Alzheimer's prevention, early detection, and the quest
      for pharmacological interventions.
AB  - Although the risk factors, biomarkers, and medications for Alzheimer's disease
      appear to be almost identical in 1993 and 2013, profound changes can de detected
      throughout this time period. This article maps these recent changes in the
      conceptualization of Alzheimer's disease, especially the emerging trend toward
      prevention. While some preventive practices (e.g., brain training) and the search
      for early signs and biomarkers (such as APOEepsilon4) have existed for a long
      time, the recent broadening of scope to include cardiovascular risk factors and
      their prevention, paired with pre-symptomatic detection of disease-specific
      biomarkers, has considerably impacted the conventional understanding of this
      syndrome and the possibilities for pharmacological and non-pharmacological
      interventions. The rationale for emphasizing multiple logics when explaining
      these changes is to avoid simplified argumentative pathways that exist among some
      scientists. 

PMID- 24668498
TI  - Total chemical synthesis of the enzyme sortase A(DeltaN59) with full catalytic
      activity.
AB  - The enzyme sortase A is a ligase which catalyzes transpeptidation reactions.1, 2
      Surface proteins, including virulence factors, that have a C terminal recognition
      sequence are attached to Gly5 on the peptidoglycan of bacterial cell walls by
      sortase A.1 The enzyme is an important anti-virulence and anti-infective drug
      target for resistant strains of Gram-positive bacteria.2 In addition, because
      sortase A enables the splicing of polypeptide chains, the transpeptidation
      reaction catalyzed by sortase A is a potentially valuable tool for protein
      science.3 Here we describe the total chemical synthesis of enzymatically active
      sortase A. The target 148 residue polypeptide chain of sortase ADeltaN59 was
      synthesized by the convergent chemical ligation of four unprotected synthetic
      peptide segments. The folded protein molecule was isolated by size-exclusion
      chromatography and had full enzymatic activity in a transpeptidation assay. Total
      synthesis of sortase A will enable more sophisticated engineering of this
      important enzyme molecule. 

PMID- 24668499
TI  - Unraveling the mechanism of water oxidation catalyzed by nonheme iron complexes.
AB  - Density functional theory (DFT) is employed to: 1) propose a viable catalytic
      cycle consistent with our experimental results for the mechanism of chemically
      driven (Ce(IV) ) O2 generation from water, mediated by nonheme iron complexes;
      and 2) to unravel the role of the ligand on the nonheme iron catalyst in the
      water oxidation reaction activity. To this end, the key features of the water
      oxidation catalytic cycle for the highly active complexes [Fe(OTf)2 (Pytacn)]
      (Pytacn: 1-(2'-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane; OTf: CF3 SO3
      (?) ) (1) and [Fe(OTf)2 (mep)] (mep: N,N'-bis(2-pyridylmethyl)-N,N'-dimethyl
      ethane-1,2-diamine) (2) as well as for the catalytically inactive [Fe(OTf)2
      (tmc)] (tmc: N,N',N'',N'''-tetramethylcyclam) (3) and [Fe(NCCH3 )((Me) Py2 CH
      tacn)](OTf)2 ((Me) Py2 CH-tacn: N-(dipyridin-2-yl)methyl)-N',N''-dimethyl-1,4,7
      triazacyclononane) (4) were analyzed. The DFT computed catalytic cycle
      establishes that the resting state under catalytic conditions is a [Fe(IV)
      (O)(OH2 )(LN4 )](2+) species (in which LN4 =Pytacn or mep) and the rate
      determining step is the O?O bond-formation event. This is nicely supported by the
      remarkable agreement between the experimental (DeltaG(?) =17.6+/-1.6 kcal mol(-1)
      ) and theoretical (DeltaG(?) =18.9 kcal mol(-1) ) activation parameters obtained
      for complex 1. The O?O bond formation is performed by an iron(V) intermediate
      [Fe(V) (O)(OH)(LN4 )](2+) containing a cis-Fe(V) (O)(OH) unit. Under catalytic
      conditions (Ce(IV) , pH 0.8) the high oxidation state Fe(V) is only
      thermodynamically accessible through a proton-coupled electron-transfer (PCET)
      process from the cis-[Fe(IV) (O)(OH2 )(LN4 )](2+) resting state. Formation of the
      [Fe(V) (O)(LN4 )](3+) species is thermodynamically inaccessible for complexes 3
      and 4. Our results also show that the cis-labile coordinative sites in iron
      complexes have a beneficial key role in the O?O bond-formation process. This is
      due to the cis-OH ligand in the cis-Fe(V) (O)(OH) intermediate that can act as
      internal base, accepting a proton concomitant to the O?O bond-formation reaction.
      Interplay between redox potentials to achieve the high oxidation state (Fe(V) ?O)
      and the activation energy barrier for the following O?O bond formation appears to
      be feasible through manipulation of the coordination environment of the iron
      site. This control may have a crucial role in the future development of water
      oxidation catalysts based on iron. 

PMID- 24668501
TI  - Genes that regulate morphogenesis and growth of the temporomandibular joint: a
      review.
AB  - Compared with the joints of the limbs, our understanding of the genes that
      regulate development and growth in the temporomandibular joint (TMJ) is fairly
      limited. Because the morphogenesis of the secondary cartilage and other intra
      articular structures in the TMJ occurs later and in a different manner than in
      the limbs, the genetic control of TMJ development might reasonably be assumed to
      differ from that in the limbs. However, studies of the specific genes regulating
      TMJ morphogenesis and growth have only begun to appear in the literature within
      the last decade. This review attempts to survey and interpret the existing
      knowledge on this topic and to suggest fruitful avenues of investigation for the
      future. Studies to date using knockout and over-expression of candidate genes
      suggest that a developmental hierarchy of joint structures exists, with condyle
      development primary. A hierarchy of gene expression also exists: Runx2 and Sox9
      expression is critical for condylar cartilage formation. Several of the other
      genes discussed in this report may regulate TMJ morphogenesis by affecting Sox9
      and Runx2 expression and control the ihh-PTHrP axis by means of these genes.

PMID- 24668500
TI  - Nicotine promotes apoptosis resistance of breast cancer cells and enrichment of
      side population cells with cancer stem cell-like properties via a signaling
      cascade involving galectin-3, alpha9 nicotinic acetylcholine receptor and STAT3.
AB  - Nicotine, a main addictive compound in tobacco smoke, has been linked to
      promotion and progression of lung, head and neck, pancreatic, and breast cancers,
      but the detailed mechanisms of cancer progression remain elusive. Here, we show
      that nicotine induces the expression of galectin-3 (an anti-apoptotic beta
      galactoside-binding lectin) in breast cancer cell line and in primary tumors from
      breast cancer patients. Nicotine-induced up regulation of galectin-3 is due to an
      increased expression of alpha9 isoform of nicotinic acetylcholine receptor
      (alpha9nAChR), which activates transcription factor STAT3 that in turn,
      physically binds to galectin-3 (LGALS3) promoter and induces transcription of
      galectin-3. Intracellular galectin-3 increased mitochondrial integrity and
      suppressed chemotherapeutic-induced apoptosis of breast cancer cell. Moreover,
      nicotine-induced enrichment of side population cells with cancer stem cell-like
      properties was modulated by galectin-3 expression and could be significantly
      reduced by transient knock down of LGALS3 and its upstream signaling molecules
      STAT3 and alpha9nAChR. Thus, galectin-3 or its upstream signaling molecule STAT3
      or alpha9nAChR could be a potential target to prevent nicotine-induced
      chemoresistance in breast cancer. 

PMID- 24668502
TI  - Quantitative correlation of the effect of process conditions on the capping
      tendencies of tablet formulations.
AB  - Capping is a mechanical defect in tablet formulation and manufacture.
      Understanding what influences tablet capping in terms of process variables and
      formulation properties and developing specialized techniques to correlate these
      variables with mechanical failures are practical interests of the pharmaceutical
      industry. Tablet compression emulator was used to rank order capping tendencies
      of a diverse sample set. The compression forces of 5-25 kN were used to compress
      round, beveled edge, and oval shape tablets. Compression speeds of 25, 40, and 80
      rpm were chosen as representative ranges for bench-to-manufacturing-scale
      processing. Tablets were tested by in-house developed nondestructive ultrasonic
      method. The measurements revealed that elastic modulus vary with different
      testing orientations that indicated elastic modulus anisotropy in tablets. It was
      shown that altering process conditions such as tooling, compression force, and
      compression speed significantly impact the capping tendencies of formulations. A
      systematic approach has been applied to develop a predictive tool to assess
      capping tendencies of formulations. The developed tool is fast, material sparing,
      and has potential to flag the risk of manufacturability issues and provide
      insight into the performance of formulations during early development.

PMID- 24668503
TI  - Effect of ancestry on behavioral variation in two species of howler monkeys
      (Alouatta pigra and A. palliata) and their hybrids.
AB  - Social differences between primate species may result from both flexible
      responses to current conditions or fixed differences across taxa, yet we know
      little about the relative importance of these factors. Here, we take advantage of
      a naturally occurring hybrid zone in Tabasco, Mexico to characterize the
      variation in social structure among two endangered howler monkey species,
      Alouatta pigra and A. palliata, and their hybrids. Work in pure populations has
      suggested that A. pigra females maintain closer proximity, exhibit higher rates
      of affiliation, and lower rates of agonism than A. palliata females, but we do
      not know what accounts for this difference. Using identical data collection and
      analysis methods across three populations, we first seek to confirm previously
      reported interspecific differences in social structure across all sexes. We next
      examine: (1) how female social relationships changed with ancestry (by comparing
      pure and hybrid individuals); (2) how female social relationships changed with
      group size (A. pigra have smaller groups than A. palliata); and (3) whether
      female social relationships differed between two taxonomic groups within a single
      forest fragment (thus controlling for ecological variation). We confirmed
      previously described species differences, including closer proximity among
      females than among males in all populations. We also found that smaller groups
      maintained closer proximity. However, even after accounting for variation in
      group size, A. pigra females had closer proximity and more affiliation than A.
      palliata females. Furthermore, differences between pigra-like and palliata-like
      hybrids paralleled differences between pure populations and persisted even after
      controlling for ecological variation. Together, our results suggest that
      flexibility cannot account for all of the social differences between A. pigra and
      A. palliata and indicate an important genetic component in primate social
      behavior.

PMID- 24668504
TI  - Brain metastases associated with germ cell tumors may be treated with
      chemotherapy alone.
AB  - BACKGROUND: The management of brain metastases in patients with germ cell tumors
      remains controversial. The authors assessed the outcome in this patient group
      after the introduction of GAMEC chemotherapy (14-day cisplatin, high-dose
      methotrexate, etoposide, and actinomycin-D with filgrastim support) and cessation
      of the routine use of cranial irradiation. METHODS: Data were recorded
      prospectively from 39 patients with germ cell tumors and concurrent brain
      metastases who received treatment before and after the advent of GAMEC after they
      relapsed on conventional cisplatin-based chemotherapy. Neurosurgery was offered
      to selected patients. Radiotherapy generally was used only as a salvage therapy
      after chemotherapy failure. The primary outcome measure was overall survival and
      was depicted using a Kaplan-Meier plot. RESULTS: The 3-year overall survival
      rates were 38% for the whole cohort, 69% for those who presented with brain
      metastases at diagnosis (group 1), and 21% and 0% for those who developed
      metastases after initial chemotherapy (group 2) and while receiving chemotherapy
      (group 3), respectively. For the whole cohort, the median overall survival was
      10.6 months (range, 5.5 months to not evaluable); and, for groups 1, 2, and 3
      individually, the overall survival was not yet reached (range, from 7.4 months to
      not evaluable), 6.2 months (range, 2.1-15.3 months), and 2.7 months (range, from
      0.6 months to not evaluable), respectively. The 3-year survival rate for those
      who received GAMEC chemotherapy was 56% compared with 27% for those who received
      chemotherapy pre-GAMEC. CONCLUSIONS: The prognosis for patients with germ cell
      tumors and brain metastases seems less bleak than previously thought. It is
      possible to achieve long-term survival with chemotherapy alone.

PMID- 24668505
TI  - Quantifying transfer after perceptual-motor sequence learning: how inflexible is
      implicit learning?
AB  - Studies of implicit perceptual-motor sequence learning have often shown learning
      to be inflexibly tied to the training conditions during learning. Since sequence
      learning is seen as a model task of skill acquisition, limits on the ability to
      transfer knowledge from the training context to a performance context indicates
      important constraints on skill learning approaches. Lack of transfer across
      contexts has been demonstrated by showing that when task elements are changed
      following training, this leads to a disruption in performance. These results have
      typically been taken as suggesting that the sequence knowledge relies on
      integrated representations across task elements (Abrahamse, Jimenez, Verwey, &
      Clegg, Psychon Bull Rev 17:603-623, 2010a). Using a relatively new sequence
      learning task, serial interception sequence learning, three experiments are
      reported that quantify this magnitude of performance disruption after selectively
      manipulating individual aspects of motor performance or perceptual information.
      In Experiment 1, selective disruption of the timing or order of sequential
      actions was examined using a novel response manipulandum that allowed for
      separate analysis of these two motor response components. In Experiments 2 and 3,
      transfer was examined after selective disruption of perceptual information that
      left the motor response sequence intact. All three experiments provided
      quantifiable estimates of partial transfer to novel contexts that suggest some
      level of information integration across task elements. However, the ability to
      identify quantifiable levels of successful transfer indicates that integration is
      not all-or-none and that measurement sensitivity is a key in understanding
      sequence knowledge representations. 

PMID- 24668509
TI  - Novel homozygous DEAF1 variant suspected in causing white matter disease,
      intellectual disability, and microcephaly.
AB  - DEAF1 encodes a transcriptional binding factor and is a regulator of serotonin
      receptor 1A. Its protein has a significant expression in the neurons of different
      brain regions and is involved in early embryonic development. In addition, its
      role in neural tube development is evident from the knockout mouse as many
      homozygotes have exencephaly. Heterozygous mutations of this gene have been
      linked to intellectual disability in addition to the gene's involvement in major
      depression, suicidal tendencies, and panic disorder. In this clinical report, we
      describe two children from a consanguineous family with intellectual disability,
      microcephaly, and hypotonia. The brain MRI of both patients showed bilateral and
      symmetrical white matter abnormalities, and one of the patients had a seizure
      disorder. Using whole exome sequencing combined with homozygosity mapping, a
      homozygous p.R226W (c.676C>T) mutation in DEAF1 was found in both patients.
      Furthermore, sequencing analysis confirmed complete segregation in tested family
      members and absence of the mutation in control cohort (n = 650). The mutation is
      located in a highly conserved structural domain that mediates DNA binding and
      therefore regulates transcriptional activity of its target molecules. This study
      indicates, for the first time to our knowledge, a hereditary role of DEAF1 in
      white matter abnormalities, microcephaly and syndromic intellectual disability.

PMID- 24668510
TI  - [At last: psychosomatic outpatient clinics according to S 118 Abs. 3 SGB V].

PMID- 24668506
TI  - Practice-related optimization and transfer of executive functions: a general
      review and a specific realization of their mechanisms in dual tasks.
AB  - Improvements in performing demanding and complex task situations are typically
      related to the optimization of executive functions and efficient behavioral
      control. The present study systematizes and reviews the optimization of different
      executive function types: Shifting, Inhibition, Updating, and Dual tasking. In
      particular, we focus on optimisations of these functions with training and on
      transfer effects of related training skills to non-trained situations. The aim of
      the study's empirical part (see also Appendix) was to investigate the specific
      mechanisms of executive functions in the context of Dual tasking, leading to
      improved dual-task performance after practice. More specifically, we tested the
      Efficient Task Instantiation (ETI) model that includes specific assumptions
      regarding practice-related improvements of executive task coordination skills:
      Dual-task performance is improved with practice because of an efficient and
      conjoint instantiation of sets of relevant task information in working memory at
      the onset of a dual task. According to our knowledge, the ETI model is one of the
      first that allows illustrating the contribution of cognitive mechanisms
      underlying practice-related improvements in performing dual tasks and the impact
      of task coordination skills on this performance. 

PMID- 24668511
TI  - [Early detection of child and adolescent depression exemplifying the role of
      screening tools in mental health care].

PMID- 24668512
TI  - [Non-substance-related addiction - behavioral addiction].

PMID- 24668513
TI  - Additional diagnostic value of implantable loop recorder in patients with initial
      diagnosis of real or apparent transient loss of consciousness of uncertain
      origin.
AB  - AIMS: Non-syncopal transient loss of consciousness (T-LOC) encompasses disorders
      that sometimes resemble syncope, and the differential diagnosis with true syncope
      may be challenging. The implantable loop recorder (ILR) is potentially useful,
      but has never been systematically assessed. The aim of the study is to evaluate
      the diagnostic value of ILR in distinguishing syncope from non-syncopal forms of
      T-LOC. METHODS AND RESULTS: We implanted an ILR in 58 patients (mean age 71 +/-
      17 years, 25 males) who had had 4.6 +/- 2.3 episodes of real or apparent T-LOC,
      in order to distinguishing epilepsy from syncope (#28), unexplained fall from
      syncope (#29), or functional pseudo-syncope from syncope (#1). During 20 +/- 13
      months of follow-up, 33 patients (57%) had a spontaneous event documented by ILR.
      A diagnosis of syncope was established by ILR documentation of an arrhythmia in
      15 (26%) patients: an asystole of 6 s (IQR 4-10 s) duration was documented at the
      time of the spontaneous event in seven patients with initial suspicion of
      epilepsy and in five patients with unexplained fall; atrial tachyarrhythmia was
      documented at the time of the spontaneous event in 1 and 1 patient, respectively,
      and ventricular tachycardia in 1 patient with unexplained fall. Conversely, in
      another 18 patients, ILR monitoring documented no significant rhythm
      abnormalities at the time of T-LOC recurrence, thus excluding an arrhythmic
      syncope. Finally, ILR was unable to document any syncopal episode in 25 (43%)
      patients. Among the 15 patients with an established diagnosis of arrhythmic
      syncope, syncope recurred during follow-up in 2 of 11 patients who were on
      pacemaker therapy and in 3 of 4 patients who were on other therapies. CONCLUSION:
      Implantable loop recorder monitoring provides additional diagnostic value in
      'difficult' patients with an initial diagnosis of non-syncopal real or apparent T
      LOC.

PMID- 24668514
TI  - Successful transbaffle catheter ablation of pulmonary vein tachycardia.

PMID- 24668515
TI  - Barriers to patients eligible for screening investigations and insertion of
      primary prevention implantable cardioverter defibrillators.
AB  - AIMS: Primary prevention (PP) implantable cardioverter defibrillator (ICD)
      implant rates in the UK are below national targets and barriers to this are not
      well known. This study was designed to identify the stages along the referral
      pathway from general to specialist care that eligible patients reach and what
      proportion eventually receive an ICD. METHODS AND RESULTS: A single institution
      database search was performed to identify all adults with severe left ventricular
      systolic dysfunction (left ventricular ejection fraction, LVEF<=35%), documented
      in the calendar year 2007. Medical records were assessed for age, heart failure
      aetiology, QRS duration, evidence of non-sustained ventricular tachycardia on
      Holter, electrophysiological study, and records of consultation with general
      physicians, cardiologists, and electrophysiologists (EPs) and reference to
      assessment of risk of sudden cardiac death and the role of ICD implantation.
      Three hundred twenty-six patients with LVEF <= 35% were identified from three
      electronic databases. Mean age was 72 +/- 12 years. Seventy-two patients
      satisfied UK National Institute for Clinical Excellence guidelines for PP ICD
      implantation and 63 eligible for further screening. Of the 135 patients, 76 (56%)
      patients reviewed by a general cardiologist did not receive ICD implantation or
      referral for further assessment. When offered, ICD acceptance rate was high (35
      vs. 3 patients who refused ICD). After seeing an EP, 8 of 47 (17%) patients were
      not offered ICD or further screening. The average age was 66.5 +/- 6.2 years and
      no patient greater than 80 years had a PP ICD. CONCLUSIONS: Failure to refer from
      the general physician to cardiology and from the cardiologist to EP is the
      principle reason for low PP ICD implant rates among eligible patients in the UK.

PMID- 24668516
TI  - The value of adrenaline in the induction of supraventricular tachycardia in the
      electrophysiological laboratory.
AB  - AIMS: The most commonly used drug for the facilitation of supraventricular
      tachycardia (SVT) induction in the electrophysiological (EP) laboratory is
      isoprenaline. Despite isoprenaline's apparent indispensability, availability has
      been problematic in some European countries. Alternative sympatomimethic drugs
      such as adrenaline have therefore been tried. However, no studies have determined
      the sensitivity and specificity of adrenaline for the induction of SVT. The
      objective of this study was to determine the sensitivity and specificity of
      adrenaline for the induction of SVT. METHODS AND RESULTS: Between February 2010
      and July 2013, 336 patients underwent an EP study for prior documented SVT. In 66
      patients, adrenaline was infused because tachycardia was not induced under basal
      conditions. This group was compared with 30 control subjects with no history of
      SVT. Programmed atrial stimulation was carried out during baseline state and
      repeated after an infusion of adrenaline (dose ranging from 0.05 mcg/kgc to 0.3
      mcg/kgc). The endpoint was the induction of SVT. Among 66 patients with a history
      of SVT but no induction under basal conditions, adrenaline facilitated induction
      in 54 patients (82%, P < 0.001). Among the 30 control subjects, SVT was not
      induced in any patient (0%) after infusion. Adrenaline was generally well
      tolerated, except for two patients (3.0%), where it had to be discontinued due to
      headache and high blood pressure or lumbar pain. CONCLUSION: Adrenaline infusion
      has a high sensitivity (82%) and specificity (100%) for the induction of SVT in
      patients with prior documented SVT. Therefore, it could serve as an acceptable
      alternative to isoprenaline, when the latter is not available.

PMID- 24668517
TI  - Clinical correlates of echocardiographic tissue velocity imaging abnormalities of
      the left atrial wall during atrial fibrillation.
AB  - AIMS: In patients with atrial fibrillation (AF), echocardiographic tissue
      velocity imaging (TVI) enables assessment of electrical and structural
      remodelling by measuring, respectively, the AF cycle length (AFCL-TVI) and the
      atrial fibrillatory wall motion velocity (AFV-TVI). We investigated the clinical
      and echocardiographic correlates of atrial remodelling assessed by TVI. METHODS
      AND RESULTS: We studied 215 patients presenting with AF. In all patients, we
      measured the AFCL-TVI and the AFV-TVI in the left atrium. Standard baseline
      characteristics were recorded. We divided patients by median value of AFV-TVI and
      AFCL-TVI to evaluate the determinants of atrial remodelling. A low AFV-TVI was
      related with a longer median duration of the current AF episode, a higher
      prevalence of significant mitral regurgitation and a thicker left ventricle (LV).
      Multivariate analysis revealed that a low AFV-TVI was independently associated
      with a longer median duration of the current AF episode [OR 0.09 (95% CI 0.03
      0.027); P < 0.001]. Univariately, a short AFCL-TVI was associated with a long
      median duration of the current AF episode, the use of anti-arrhythmic drugs, a
      lower LV ejection fraction (LVEF) and a smaller left atrial volume index (LAVI).
      Multivariate analysis revealed that LVEF [OR 1.48 (95% CI 1.09-2.01); P = 0.013]
      and LAVI [OR 1.37 (95% CI 1.08-1.74); P = 0.010] were independently associated
      with AFCL-TVI. CONCLUSION: This study investigated the clinical and
      echocardiographic correlates of atrial remodelling assessed by TVI. The AFV-TVI
      is reduced in patients with a long AF duration and who have mitral regurgitation.
      In addition, the AFCL is long if LAVI is high and LVEF preserved. Tissue velocity
      imaging parameters measured during AF may be helpful to characterize the degree
      of atrial remodelling and optimize treatment.

PMID- 24668518
TI  - Linker rectifiers for covalent attachment of transition-metal catalysts to metal
      oxide surfaces.
AB  - Linkers that favor rectification of interfacial electron transfer are likely to
      be required for efficient photo-driven catalysis of multi-electron reactions at
      electrode surfaces. Design principles are discussed, together with the synthesis
      and characterization of a specific pair of molecular linkers, related by
      inversion of the direction of an amide bond in the heart of the molecule. The
      linkers have a terpyridyl group that can covalently bind Mn as in a well-known
      water oxidation catalyst and an acetylacetonate group that allows attachment to
      TiO2 surfaces. The appropriate choice of the sense of the amide linkage yields
      directionality of interfacial electron transfer, essential to enhance electron
      injection and slow back-electron transfer. Support comes from electron
      paramagnetic resonance and terahertz spectroscopic measurements, as well as
      computational modeling characterizing the asymmetry of electron transfer
      properties. 

PMID- 24668519
TI  - Coffee and cancer risk, epidemiological evidence, and molecular mechanisms.
AB  - Although early studies suggested that coffee consumption might increase risk of
      some cancers, more comprehensive epidemiological and experimental data now
      generally indicate either neutral or beneficial effects. In this review, we
      summarize the current evidence for associations between breast, prostate,
      colorectal, and liver cancers and the consumption of coffee, and discuss the
      experimental evidence for potential chemopreventive mechanisms of coffee and
      coffee constituents. The epidemiological evidence consistently indicates that
      coffee protects against liver cancer, and also point toward protective effects
      for risk of colorectal cancers (with relative risks of 0.50 (95% CI: 0.42-0.59)
      and 0.83 (95% CI: 0.75-0.92), respectively, in the most recent meta-analyses).
      There seems to be no association between the overall risk of breast and prostate
      cancer and coffee intake. However, for subgroups such as postmenopausal breast
      cancers, advanced prostate cancers, and breast and prostate cancer survivors, an
      inverse association with coffee intake is indicated. Potential mechanisms for
      chemopreventive effects of coffee phytochemicals includes inhibition of oxidative
      stress and oxidative damage, regulation of DNA repair, phase II enzymatic
      activity, apoptosis, inflammation, as well as having antiproliferative,
      antiangiogenetic effects and antimetastatic effects. The experimental evidence
      for effects of coffee and coffee constituents on each of these processes is
      discussed. 

PMID- 24668521
TI  - Accessing medical physics, biomedical engineering and radiopharmaceutical
      expertise.

PMID- 24668520
TI  - Two-dimensional imaging in a lightweight portable MRI scanner without gradient
      coils.
AB  - PURPOSE: As the premiere modality for brain imaging, MRI could find wider
      applicability if lightweight, portable systems were available for siting in
      unconventional locations such as intensive care units, physician offices,
      surgical suites, ambulances, emergency rooms, sports facilities, or rural
      healthcare sites. METHODS: We construct and validate a truly portable (<100 kg)
      and silent proof-of-concept MRI scanner which replaces conventional gradient
      encoding with a rotating lightweight cryogen-free, low-field magnet. When rotated
      about the object, the inhomogeneous field pattern is used as a rotating spatial
      encoding magnetic field (rSEM) to create generalized projections which encode the
      iteratively reconstructed two-dimensional (2D) image. Multiple receive channels
      are used to disambiguate the nonbijective encoding field. RESULTS: The system is
      validated with experimental images of 2D test phantoms. Similar to other
      nonlinear field encoding schemes, the spatial resolution is position dependent
      with blurring in the center, but is shown to be likely sufficient for many
      medical applications. CONCLUSION: The presented MRI scanner demonstrates the
      potential for portability by simultaneously relaxing the magnet homogeneity
      criteria and eliminating the gradient coil. This new architecture and encoding
      scheme shows convincing proof of concept images that are expected to be further
      improved with refinement of the calibration and methodology.

PMID- 24668523
TI  - Pseudothrombocytopenia in a child with Dengue.

PMID- 24668522
TI  - Copper-catalyzed electrophilic amination of heteroarenes and arenes by C-H
      zincation.
AB  - Direct amination of heteroarenes and arenes has been achieved in a one-pot C?H
      zincation/copper-catalyzed electrophilic amination procedure. This amination
      method provides an efficient and rapid approach to access a diverse range of
      heteroaromatic and aromatic amines including those previously inaccessible using
      C?H amination methods. The mild reaction conditions and good functional-group
      compatibility demonstrate its great potential for the synthesis of important and
      complex amines. 

PMID- 24668524
TI  - Miliary pattern on chest imaging in an immunocompetent child.

PMID- 24668526
TI  - Automated detection and quantification of clusters of malapposed and uncovered
      intracoronary stent struts assessed with optical coherence tomography.
AB  - To date, accurate quantification and localization of malapposed and uncovered
      struts needs manual and time consuming analysis of large datasets. To develop an
      algorithm for automated detection and quantification of clusters of malapposed
      and uncovered struts in optical coherence tomography (OCT) pullbacks, including
      comprehensive information about their three-dimensional spatial distribution. 64
      lesions in 64 patients treated with drug-eluting stent underwent assessment with
      OCT immediately after implantation and at 9-month follow-up (55 patients). An
      automated algorithm was used to detect and quantify stent strut malapposition at
      baseline and coverage at follow-up on an individual strut level. We subsequently
      applied an algorithm for the automated clustering of malapposed and uncovered
      struts and for the quantification of clusters' properties. In the 64 baseline
      examinations, a total of 24,013 struts were analyzed, of which 1,519 (6 %) were
      malapposed. Most malapposed struts (78 %) occurred in clusters and more than half
      of patients had malapposition clusters. The mean number of struts per cluster was
      19.7 +/- 11.8 with a mean malapposition distance of 213 +/- 66 MUm. In the 55
      follow-up pullbacks, a total of 20,484 struts were analyzed, of which 1,320 (6 %)
      were uncovered. Again, most uncovered struts (85 %) occurred in clusters. The
      mean number of struts per cluster was 21.1 +/- 14.7. We developed an automated
      algorithm for studying clustering of malapposed or uncovered struts. This
      algorithm might facilitate future investigations of the prognostic impact of
      clusters of malapposed or uncovered struts.

PMID- 24668527
TI  - Autonomy in chimpanzees.
AB  - Literature on the mental capacities and cognitive mechanisms of the great apes
      has been silent about whether they can act autonomously. This paper provides a
      philosophical theory of autonomy supported by psychological studies of the
      cognitive mechanisms that underlie chimpanzee behavior to argue that chimpanzees
      can act autonomously even though their psychological mechanisms differ from those
      of humans. Chimpanzees satisfy the two basic conditions of autonomy: (1) liberty
      (the absence of controlling influences) and (2) agency (self-initiated
      intentional action), each of which is specified here in terms of conditions of
      understanding, intention, and self-control. In this account, chimpanzees make
      knowledge-based choices reflecting a richly information-based and socially
      sophisticated understanding of the world. Finally, two major theories of autonomy
      (Kantian theory and two-level theory) are rejected as too narrow to adequately
      address these issues, necessitating the modifications made in the present
      approach. 

PMID- 24668525
TI  - Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and
      serum-derived viral RNA-containing particles are infectious in vitro.
AB  - Human pegivirus (HPgV; previously called GB virus C/hepatitis G virus) has
      limited pathogenicity, despite causing persistent infection, and is associated
      with prolonged survival in human immunodeficiency virus-infected individuals.
      Although HPgV RNA is found in and produced by T- and B-lymphocytes, the primary
      permissive cell type(s) are unknown. We quantified HPgV RNA in highly purified
      CD4(+) and CD8(+) T-cells, including naive, central memory and effector memory
      populations, and in B-cells (CD19(+)), NK cells (CD56(+)) and monocytes (CD14(+))
      using real-time reverse transcription-PCR. Single-genome sequencing was performed
      on viruses within individual cell types to estimate genetic diversity among cell
      populations. HPgV RNA was present in CD4(+) and CD8(+) T-lymphocytes (nine of
      nine subjects), B-lymphocytes (seven of ten subjects), NK cells and monocytes
      (both four of five). HPgV RNA levels were higher in naive (CD45RA(+)) CD4(+)
      cells than in central memory and effector memory cells (P<0.01). HPgV sequences
      were highly conserved among subjects (0.117+/-0.02 substitutions per site; range
      0.58-0.14) and within subjects (0.006+/-0.003 substitutions per site; range 0.006
      0.010). The non-synonymous/synonymous substitution ratio was 0.07, suggesting a
      low selective pressure. Carboxyfluorescein succinimidyl ester (CFSE)-labelled
      HPgV RNA-containing particles precipitated by a commercial exosome isolation
      reagent delivered CSFE to uninfected monocytes, NK cells and T- and B
      lymphocytes, and HPgV RNA was transferred to PBMCs with evidence of subsequent
      virus replication. Thus, HPgV RNA-containing serum particles including
      microvesicles may contribute to delivery of HPgV to PBMCs in vivo, explaining the
      apparent broad tropism of this persistent human RNA virus.

PMID- 24668528
TI  - Mechanisms and models of endoplasmic reticulum stress in chondrodysplasia.
AB  - Chondrodysplasias are a group of genetic disorders that affect the development
      and growth of cartilage. These disorders can result in extreme short stature,
      craniofacial defects, joint malformation, and early osteoarthritis; severely
      impacting quality of life for affected individuals. Many chondrodysplasias are
      caused by mutations in genes encoding cartilage extracellular matrix (ECM)
      proteins. These mutations typically result in synthesis of abnormal proteins that
      are improperly folded, and hence inappropriately retained within the endoplasmic
      reticulum (ER) of the cell, activating ER stress and the unfolded protein
      response (UPR), an adaptive cellular response to minimize production of the
      mutant protein and/or to enhance protein folding, degradation or export. If
      prolonged, activation of the UPR causes apoptotic cell death. Many human
      disorders have an underlying mechanism in UPR activation, and targeting ER stress
      pathways is showing promise for development of therapeutics for these conditions.
      Understanding and modeling the UPR in chondrodysplasia will be essential to
      advance such targeted approaches for the benefit of chondrodysplasia patients.
      The focus of this review is to compare the mechanistic sequelae of ECM protein
      mutations in chondrodysplasia that may cause chondrocyte ER stress and UPR
      activation, and to present current and future directions in chondrodysplasia
      disease modeling and therapeutic intervention.

PMID- 24668530
TI  - 14N nuclear quadrupole resonance study of polymorphism in famotidine.
AB  - (14)N nuclear quadrupole resonance (NQR) in two known polymorphs of famotidine
      was measured. At room temperature, seven quadrupolar sets of transition
      frequencies (nu(+), nu(-), and nu(0)) corresponding to seven different nitrogen
      sites in the crystal structure of each of the two polymorphs were found. This
      confirms the expected ability of NQR to distinguish polymorph B from its analog
      A. NQR can also measure their ratio in a solid mixture and in the final dosage
      form, that is, a tablet. The NQR frequencies, line shapes, and tentative
      assignation to all seven molecular (14)N atoms were obtained. Unravelment of
      these two entangled NQR spectra presents a valuable contribution to the NQR
      database and enables studies of some possible correlations therein. Moreover,
      nondestructive (14)N NQR studies of commercial famotidine tablets can reveal some
      details of the drug fabrication process connected with compression.

PMID- 24668529
TI  - Ossification of abdominal scar tissue: a case series with a translational review
      on its development.
AB  - PURPOSE: Bone formation in abdominal scar tissue is a form of heterotopic
      ossification. It is a rare and underreported phenomenon following abdominal
      surgery. Heterotopic ossification (HO) is the formation of bone where normally no
      bone is present and two theories on its pathogenesis prevail: (1) physical
      dislocation of small bony fragments from the xyphoid process or os pubis into the
      wound, (2) differentiation of locally available multipotent mesenchymal stromal
      cells into osteoblasts resulting in the calcification of extracellular matrix.
      Multipotent mesenchymal stromal cells can differentiate into different cell types
      by exposing them to different stimuli. We hypothesize that pro-osteogenic signals
      derived from e.g., macrophages steers multipotent mesenchymal stromal cells
      involved in the wound healing towards osteogenesis. METHODS: In a retrospective
      case study we analyzed ossified tissue, patient demographics, medical history,
      number of laparotomies, scar location, indication for surgery and time in which
      HO occurred. RESULTS: Ten (8 male, 2 female) patients had proven HO. The mean age
      was 62 (46-80) years. The mean time for HO to occur was 99 (24-382) days after
      the previous laparotomy. The mean number of relaparotomies was 3 (1-9).
      CONCLUSION: We conclude that ossification of abdominal scar tissue is a rare but
      innocent finding and provides interesting leads to other fields of research.

PMID- 24668531
TI  - Pulmonary complications of connective tissue disease.

PMID- 24668532
TI  - Cross-disciplinary collaboration in connective tissue disease-related lung
      disease.
AB  - Lung disease is a common manifestation of connective tissue disease (CTD) and is
      associated with significant morbidity and mortality. The evaluation of lung
      disease, and interstitial lung disease (ILD) in particular, in patients with CTD
      is complex because of the heterogeneity of the CTDs, the varied types and degrees
      of severity of ILD encountered, and because ILD can be identified at any point in
      time in these patients. Cross-disciplinary, thorough evaluations are needed when
      CTD patients develop ILD or when evaluating ILD patients for the presence of
      occult CTD. Determining that ILD is associated with an established CTD requires
      the exclusion of alternative etiologies, and thorough assessments of the clinical
      features of both the CTD and ILD. The detection of occult CTD in patients with
      "idiopathic" ILD requires careful attention to the demographic profile,
      historical clues, subtle physical examination findings, specific autoantibody
      positivity, radiological and histopathological features, and can be optimized by
      a multidisciplinary approach that includes rheumatological collaboration. Not all
      patients with CTD-associated ILD require pharmacological therapy, and management
      decisions should consider pace and severity of the disease, intra- and
      extrathoracic features of activity and can be optimized by cross-disciplinary
      collaboration. 

PMID- 24668533
TI  - High-resolution computed tomography of the pulmonary manifestations of connective
      tissue diseases.
AB  - Pulmonary disease is common in patients with connective tissue disease (CTD) and
      confers significant morbidity and mortality. High-resolution computed tomography
      (HRCT) provides considerable information regarding the distribution and severity
      of thoracic disease in CTD. Different anatomical compartments of the lung can be
      simultaneously affected in a given individual. Furthermore, lung injury may not
      be solely related to the underlying CTD, but may be caused by treatment or
      infections. Finally, the risk of developing cancer is increased in patients with
      certain CTDs. In this review, the HRCT manifestations of CTD are initially
      discussed with respect to the different compartments involved, followed by a
      description of the spectrum of pulmonary disease commonly occurring in specific
      CTDs. 

PMID- 24668534
TI  - Biomarkers in connective tissue disease-associated interstitial lung disease.
AB  - This article reviews major biomarkers in serum and bronchoalveolar lavage fluid
      (BALF) with respect to their diagnostic and prognostic value in connective tissue
      disease-associated interstitial lung disease (CTD-ILD). In some CTD such as
      systemic sclerosis (SSc), the incidence of ILD is up to two-third of patients,
      and currently ILD represents the leading cause of death in SSc. Because of the
      extremely variable incidence and outcome of ILD in CTD, progress in the discovery
      and validation of biomarkers for diagnosis, prognosis, patients' subtyping,
      response to treatment, or as surrogate endpoints in clinical trials is extremely
      important. In contrast to idiopathic interstitial pneumonias, autoantibodies play
      a crucial role as biomarkers in CTD-ILD because their presence is strictly linked
      to the pathogenesis and tissue damage. Patterns of autoantibodies, for instance,
      anticitrullinated peptide antibodies in rheumatoid arthritis or aminoacyl-tRNA
      synthetases (ARS) in polymyositis/dermatomyositis, have been found to correlate
      with the presence and occasionally with the course of ILD in CTD. Besides
      autoantibodies, an increase in serum or BALF of a biomarker of pulmonary origin
      may be able to predict or reflect the development of fibrosis, the impairment of
      lung function, and ideally also the prognosis. Promising biomarkers are lung
      epithelium-derived proteins such as KL-6 (Krebs von den Lungen-6), SP-D
      (surfactant protein-D), SP-A (surfactant protein-A), YKL-40 (chitinase-3-like
      protein 1 [CHI3L1] or cytokines such as CCL18 [chemokine (C-C) motif ligand 18]).
      In the future, genetic/epigenetic markers, such as human leukocyte antigen (HLA)
      haplotypes, single nucleotide polymorphisms, and micro-RNA, may help to identify
      subtypes of patients with different needs of management and treatment strategies.

PMID- 24668535
TI  - Pulmonary pathology in connective tissue disease.
AB  - A significant proportion of patients with autoimmune connective tissue disease
      (CTD) show lung involvement that results in clinical interstitial lung disease
      (ILD). Surgical lung biopsy is helpful for diagnosis of CTD-ILD in many cases. In
      this review, we discuss the histologic manifestations of different types of CTD
      ILD, focusing on patterns of disease and their differential diagnoses. Acquired
      autoimmune connective tissue diseases will be covered in this review, while lung
      involvement in vasculitides, heritable connective tissue disorders, and drug
      induced CTD-like conditions will not be discussed. 

PMID- 24668536
TI  - Interstitial lung disease in systemic sclerosis.
AB  - Despite many unanswered questions regarding the pathogenesis of interstitial lung
      disease in systemic sclerosis (SSc-ILD) and the lack of accurate epidemiological
      risk factors, there have been major advances in the identification and prognostic
      evaluation of SSc-ILD. The evaluation of disease severity is a multidisciplinary
      exercise, requiring the integration of pulmonary function tests, high-resolution
      computed tomography data, and symptomatic severity and these factors all need to
      be considered in the detection of disease progression. Except in a minority of
      patients with reversible inflammatory disease, the primary goal of treatment is
      the prevention of disease progression. Current treatment regimens are centered on
      immunosuppressive therapy with controlled treatment data largely confined to the
      use of cyclophosphamide. The results of two controlled trials indicate that
      cyclophosphamide therapy is appropriate in SSc-ILD patients with extensive
      fibrotic lung involvement. There is a need to broaden therapeutic approaches with
      the exploration of rituximab (based on recent pilot data) and antifibrotic
      agents, shown to have treatment effects in other fibrotic interstitial lung
      diseases. However, it is also important to avoid the overtreatment of SSc-ILD
      patients with limited nonprogressive lung involvement. In that setting, an
      initial policy of nonintervention but meticulous observation ("masterful
      inactivity with cat-like observation") is often warranted. 

PMID- 24668537
TI  - Rheumatoid arthritis and lung disease: from mechanisms to a practical approach.
AB  - Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease
      characterized by joint inflammation and, in a proportion of patients, extra
      articular manifestations (EAM). Lung disease, either as an EAM of the disease,
      related to the drug therapy for RA, or related to comorbid conditions, is the
      second commonest cause of mortality. All areas of the lung including the pleura,
      airways, parenchyma, and vasculature may be involved, with interstitial and
      pleural disease and infection being the most common problems. High-resolution
      computed tomography of the chest forms the basis of investigation and when
      combined with clinical information and measures of physiology, a
      multidisciplinary team can frequently establish the diagnosis without the need
      for an invasive biopsy procedure. The most frequent patterns of interstitial lung
      disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial
      pneumonia (NSIP), with some evidence for the prognosis being better than for the
      idiopathic equivalents. Risk factors depend on the type of disease but for ILD
      (mainly UIP and NSIP) include smoking, male gender, human leukocyte antigen
      haplotype, rheumatoid factor, and anticitrullinated protein antibodies (ACPAs).
      Citrullination of proteins in the lung, frequently thought to be incited by
      smoking, and the subsequent development of ACPA appear to play an important role
      in the development of lung and possibly joint disease. The biologic and
      nonbiological disease modifying antirheumatic drugs (DMARDs) have had a
      substantial impact on morbidity and mortality from RA, and although there
      multiple reports of drug-related lung toxicity and possible exacerbation of
      underlying ILD, overall these reactions are rare and should only preclude the use
      of DMARDs in a minority of patients. Common scenarios facing pulmonologists and
      rheumatologists are addressed using the current best evidence; these include
      screening the new patient; monitoring and choosing RA treatment in the presence
      of subclinical disease; treating deteriorating ILD; and establishing a diagnosis
      in a patient with an acute respiratory presentation. 

PMID- 24668538
TI  - Pulmonary manifestations of polymyositis/dermatomyositis.
AB  - The idiopathic inflammatory myopathies are a group of connective tissue diseases
      marked by varying degrees of muscle inflammation and clinical involvement of
      multiple organs, most notably, the lung. Pulmonary manifestations consist
      primarily of interstitial lung disease (ILD), which is associated with
      significant morbidity and mortality in myositis patients. Several myositis
      specific antibodies have been discovered, as well as antibodies targeting various
      aminoacyl-tRNA synthetase enzymes. These antibodies are associated with various
      clinical features and a risk for developing ILD, and their presence carries a
      prognostic value in myositis patients. Steroids remain the first-line treatment
      for myositis-associated ILD and the antisynthetase syndrome, though other
      traditional immunosuppressants have demonstrated efficacy in numerous studies.
      While a majority of patients experience either stabilization or improvement in
      lung imaging and function, fatal progression is still reported in a significant
      number of cases. Further research is needed to develop more effective and
      targeted therapies. 

PMID- 24668539
TI  - Pulmonary manifestations of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic inflammatory disease,
      characterized serologically by an autoantibody response to nucleic antigens, and
      clinically by injury and/or malfunction in any organ system. During their disease
      course, up to 50% of SLE patients will develop lung disease. Pulmonary
      manifestations of SLE include pleuritis (with or without effusion), inflammatory
      and fibrotic forms of interstitial lung disease, alveolar hemorrhage, shrinking
      lung syndrome, pulmonary hypertension, airways disease, and thromboembolic
      disease. Two major themes inform our understanding of SLE-associated pulmonary
      manifestations: first, the presence of specific autoantibodies correlates with
      the presence of certain pulmonary manifestations and second, vascular injury
      marks a common pathophysiologic thread among the various SLE-related lung
      diseases. This review will focus on the clinical presentation, pathogenesis,
      pathology, management, and prognosis of these SLE-associated lung conditions. 

PMID- 24668540
TI  - Pulmonary involvement in Sjogren syndrome.
AB  - Sjogren syndrome (SS) is a chronic autoimmune disease characterized by
      lymphocytic inflammation of exocrine glands and a variety of extraglandular
      sites. Lung involvement as defined by symptoms and either pulmonary function
      testing or radiographic abnormalities occurs in approximately 10 to 20% of
      patients. Subclinical lung disease is even more frequent and often includes
      evidence of small airways disease and airway inflammation. In general, patients
      will have evidence of both airway and interstitial lung disease by radiographs
      and pathology. Bronchiolitis and bronchiectasis are the most common airway
      manifestations while the interstitial pathologies associated with SS include
      nonspecific interstitial pneumonitis, usual interstitial pneumonitis, and
      lymphocytic interstitial pneumonitis. Patients with SS are also at an increased
      risk of lymphoma. A protean of other lung abnormalities including amyloidosis,
      granulomatous lung disease, pseudolymphoma, pulmonary hypertension, and pleural
      disease have been described. 

PMID- 24668541
TI  - Immunosuppression for connective tissue disease-related pulmonary disease.
AB  - With improvements in the systemic treatment of the various connective tissue
      diseases (CTDs) the pulmonary complications of these conditions are now, for many
      patients, the major cause of morbidity and impaired quality of life. Furthermore,
      at least in scleroderma, pulmonary disease has become the leading cause of death
      for this patient group. Although, the pathogenesis of CTD-related pulmonary
      disease is poorly understood there is an assumption that it arises as a sequelae
      of immune-mediated injury to the lung. As a result, immunosuppressant agents form
      the mainstay of treatment for pulmonary disease occurring in the context of CTD.
      There is, however, a paucity of clinical trial data available to inform treatment
      decisions across the spectrum of CTD-related pulmonary disease. The best
      available evidence has been generated in scleroderma-associated interstitial lung
      disease. Therefore, treatment decisions are informed by registry data, case
      series, and individual case reports. With this in mind, corticosteroids together
      with azathioprine and mycophenolate mofetil are widely used for the management of
      mild disease or as a maintenance therapy, while cyclophosphamide and rituximab
      have emerged as treatments for refractory or rapidly progressive disease. This
      article examines the data underpinning the use of different immunosuppressants in
      CTD-associated pulmonary disease while highlighting limitations in the existing
      knowledge base and identifying questions for future clinical study. 

PMID- 24668542
TI  - Supportive care for patients with pulmonary complications of connective tissue
      disease.
AB  - Patients with connective tissue disease often suffer from pulmonary
      complications, including interstitial lung disease and pulmonary hypertension.
      Supportive care for these patients aims to relieve symptoms and improve activity
      level and quality of life. A holistic approach to the management of patients with
      advanced connective tissue disease-associated pulmonary disorders includes a full
      assessment of patient symptoms as well as a careful search for side effects of
      treatment and treatable comorbidities. This article addresses supportive measures
      such as supplemental oxygen and pulmonary rehabilitation. Issues related to
      quality of life, sleep disturbances, and identification of mood disorders are
      discussed. In addition, we review significant comorbidities, including
      cardiovascular disease, glucocorticoid-induced osteoporosis, and gastroesophageal
      reflux disease. Essential facets of advanced lung disease, including mechanical
      ventilation, lung transplantation, end-of-life care, and hospice, are covered. 

PMID- 24668543
TI  - Short-term insulin requirements following gastric bypass surgery in severely
      obese women with type 1 diabetes.
AB  - BACKGROUND: In severely obese type 2 diabetes patients, gastric bypass surgery
      (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced
      doses of insulin and other medications. Data regarding the effects of GB on
      severely obese patients with type 1 diabetes are limited. METHODS: Severely obese
      women with type 1 diabetes (n = 9) were studied immediately before and after GB
      (7.7 +/- 5.8 weeks, mean +/- SD). RESULTS: On average, GB reduced mean BMI by 11%
      and mean HbA1c by 0.9% (from 8.0 to 7.1%), with a parallel 38% decrease in basal
      insulin requirements (expressed per kilogram of body weight). CONCLUSION: GB
      rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women
      with type 1 diabetes. However, physiologic insulin replacement remains necessary
      in patients with type 1 diabetes.

PMID- 24668544
TI  - Two-year outcomes for medicaid patients undergoing laparoscopic Roux-en-Y gastric
      bypass: a case-control study.
AB  - BACKGROUND: Millions of patients will be added to Medicaid programs throughout
      the country due to expansion driven by the Affordable Care Act. Since 90 % of
      state Medicaid programs cover bariatric surgery, the outcomes of Medicaid
      patients will be important to study. We performed a retrospective analysis to
      compare outcomes between Medicaid and non-Medicaid bariatric surgery patients
      over a two-year period. METHODS: All patients who underwent a laparoscopic Roux
      en-Y gastric bypass at The Ohio State University Medical Center from January 2008
      April 2011 were identified. Of these 609 patients, 30 Medicaid patients were
      identified and compared to 90 randomly selected non-Medicaid patients (1:3 case
      control). Preoperative data and postoperative outcome data (weight loss,
      comorbidity resolution, complications, and mortality) were obtained from
      electronic medical records. Descriptive statistical analyses were performed to
      compare categorical and continuous variables. RESULTS: Medicaid patients had a
      significantly higher average BMI (58.4 vs. 49.5; p < 0.001) and higher rates of
      comorbidities. Over a 90-day postoperative period, Medicaid patients experienced
      a higher wound complication rate (20.0 vs. 5.6 %; p = 0.03) and visited the ER
      more frequently (33.3 vs. 10.0 %; p = 0.007) but had similar rates of medical
      complications compared to non-Medicaid patients. The Medicaid cohort lost 52.1 %
      of its excess body weight vs. 64.6 % for the non-Medicaid cohort (p = 0.02) over
      a two-year period. There were no significant differences in comorbidity
      resolution, anastomotic complications, or mortality after 2 years of follow-up.
      CONCLUSION: Despite being a higher risk cohort, Medicaid patients undergoing
      laparoscopic Roux-en-Y gastric bypass had similar long-term outcomes compared to
      non-Medicaid patients.

PMID- 24668545
TI  - Metastatic lymph node ratio can further stratify prognosis in rectal cancer
      patients treated with preoperative radiotherapy: a population-based analysis.
AB  - Recent studies have shown that it is not only the absolute number of involved
      lymph nodes (LNs) but also the ratio of metastatic lymph node that confers
      prognostic information. However, the impact of the lymph node ratio (LNR) on the
      prognosis of rectal cancer treated with preoperative radiotherapy is still not
      fully studied. In this study, Surveillance, Epidemiology, and End Results (SEER)
      registered rectal cancer patients treated with preoperative radiotherapy (preop
      RT) with LN metastasis were evaluated using multivariate Cox regression analysis
      to determine the prognostic role of the LNR. LNR optimal cutoff was identified by
      X-tile. The rationale of yielding pathological node stage (yp-N stage) and
      yielding pathological lymph node ratio stage (yp-rN stage) (LNR stage) was
      further combined for analysis. For the results, X-tile program determined 0.28
      and 0.68 as optimal cutoff values in terms of survival in 1,872 rectal cancer
      patients treated with preoperative radiotherapy. yp-rN was significantly
      associated with 5-year rectal cancer cause-specific survival (RCSS) (P < 0.001).
      In a multivariate analysis, yp-rN was a significant independent prognostic factor
      for RCSS (hazard ratios, 1.277 and 1.631; P < 0.001). yp-rN had a prognostic
      impact on RCSS in patients with yp-N1 and yp-N2 subgroup. yp-N stage also had
      influenced on RCSS in all yp-rN stage. The yp-rN stage can be used together with
      the yp-N stage to select high-risk patients for postoperative treatment.

PMID- 24668546
TI  - Molecular mechanism of TGF-beta signaling pathway in colon carcinogenesis and
      status of curcumin as chemopreventive strategy.
AB  - Colon cancer is one of the third most common cancer in man, the second most
      common cancer in women worldwide, and the second leading cause of mortality in
      the USA. There are a number of molecular pathways that have been implicated in
      colon carcinogenesis, including TGF-beta/Smad signaling pathway. TGF-beta
      (transforming growth factor-beta) signaling pathway has the potential to regulate
      various biological processes including cell growth, differentiation, apoptosis,
      extracellular matrix modeling, and immune response. TGF-beta signaling pathway
      acts as a tumor suppressor, but alterations in TGF-beta signaling pathway
      promotes colon cancer cell growth, migration, invasion, angiogenesis, and
      metastasis. Here we review the role of TGF-beta signaling cascade in colon
      carcinogenesis and multiple molecular targets of curcumin in colon
      carcinogenesis. Elucidation of the molecular mechanism of curcumin on TGF-beta
      signaling pathway-induced colon carcinogenesis may ultimately lead to novel and
      more effective treatments for colon cancer. 

PMID- 24668547
TI  - Differential expression of histone deacetylase and acetyltransferase genes in
      gastric cancer and their modulation by trichostatin A.
AB  - Gastric cancer is still the second leading cause of cancer-related death
      worldwide, even though its incidence and mortality have declined over the recent
      few decades. Epigenetic control using histone deacetylase inhibitors, such as
      trichostatin A (TSA), is a promising cancer therapy. This study aimed to assess
      the messenger RNA (mRNA) levels of three histone deacetylases (HDAC1, HDAC2, and
      HDAC3), two histone acetyltransferases (GCN5 and PCAF), and two possible targets
      of these histone modifiers (MYC and CDKN1A) in 50 matched pairs of gastric tumors
      and corresponding adjacent nontumors samples from patients with gastric
      adenocarcinoma, as well as their correlations and their possible associations
      with clinicopathological features. Additionally, we evaluated whether these genes
      are sensitive to TSA in gastric cancer cell lines. Our results demonstrated
      downregulation of HDAC1, PCAF, and CDKN1A in gastric tumors compared with
      adjacent nontumors (P < 0.05). On the other hand, upregulation of HDAC2, GCN5,
      and MYC was observed in gastric tumors compared with adjacent nontumors (P <
      0.05). The mRNA level of MYC was correlated to HDAC3 and GCN5 (P < 0.05), whereas
      CDKN1A was correlated to HDAC1 and GCN5 (P < 0.05 and P < 0.01, respectively). In
      addition, the reduced expression of PCAF was associated with intestinal-type
      gastric cancer (P = 0.03) and TNM stages I/II (P = 0.01). The increased
      expression of GCN5 was associated with advanced stage gastric cancer (P = 0.02)
      and tumor invasion (P = 0.03). The gastric cell lines treated with TSA showed
      different patterns of histone deacetylase and acetyltransferase mRNA expression,
      downregulation of MYC, and upregulation of CDKN1A. Our findings suggest that
      alteration of histone modifier genes play an important role in gastric
      carcinogenesis, contributing to MYC and CDKN1A deregulation. In addition, all
      genes studied here are modulated by TSA, although this modulation appears to be
      dependent of the genetic background of the cell line.

PMID- 24668548
TI  - Susceptibility to hepatocellular carcinoma in the Chinese population-
      associations with interleukin-6 receptor polymorphism.
AB  - Hepatocellular carcinoma (HCC) is one of the most deadly malignant diseases in
      the world. Genetic variations in cytokine genes may have an effect on the immune
      and inflammatory responses which are associated with HBV-HCC. The interleukin-6
      (IL-6) receptor is known to be mainly expressed by hepatocytes, neutrophils,
      monocytes/macrophages, and some lymphocytes, which have been used as prognostic
      markers in a variety of inflammatory diseases such as rheumatoid arthritis,
      asthma, and Crohn's disease. To determine the association of IL-6 receptor (IL
      6R) polymorphism with the risk of hepatocellular carcinoma (HCC) development in
      the Chinese population, a hospital based case-control study was designed
      consisting of 192 subjects with HCC and 192 healthy control subjects. Our results
      revealed no risk associations (p = 0.064) with rs6684439 CT genotypes. However,
      rs6684439 TT genotypes were associated with a significantly decreased risk of HBV
      related HCC compared with the CC genotype (odds ratio (OR) = 0.469, 95 %
      confidence interval (CI) 0.228-0.967, p = 0.040). The data also revealed that
      subjects with the T allele appeared to have a lower susceptibility to HBV-related
      HCC than those with the C allele (OR = 0.657, 95 % CI 0.476-0.907, p = 0.011).
      The present study supports the view that variants in the rs6684439 SNP of IL-6R
      is associated with a lower risk of HBV-related HCC, and this could provide
      valuable clues to understanding the mechanisms underlying susceptibility to this
      malignant disease. Replication and further functional studies should be carried
      out in the future using larger samples.

PMID- 24668550
TI  - Protein S-nitrosylation in preconditioning and postconditioning.
AB  - The coronary artery disease is a leading cause of death and morbidity worldwide.
      This disease has a complex pathophysiology that includes multiple mechanisms.
      Among these is the oxidative/nitrosative stress. Paradoxically,
      oxidative/nitrosative signaling plays a major role in cardioprotection against
      ischemia/reperfusion injury. In this context, the gas transmitter nitric oxide
      may act through several mechanisms, such as guanylyl cyclase activation and via S
      nitrosylation of proteins. The latter is a covalent modification of a protein
      cysteine thiol by a nitric oxide-group that generates an S-nitrosothiol. Here, we
      report data showing that nitric oxide and S-nitrosylation of proteins play a
      pivotal role not only in preconditioning but also in postconditioning
      cardioprotection.

PMID- 24668549
TI  - A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency.
AB  - A girl patient born to healthy nonconsanguineous parents was referred at age 3
      years and 2 months to our genetics department for testing due to developmental
      delay and postnatal microcephaly. Initial clinical evaluation revealed an overall
      developmental delay, mildly dysmorphic features, thin, sparse fair hair, and fair
      skin. Postnatal microcephaly and progressive ataxia and spasticity appeared
      later. Array CGH karyotyping showed a 333 kb de novo microdeletion on 3p22
      covering the entire genomic sequence of a single gene, CTNNB1, which codes for
      beta-catenin. beta-catenin is a sub-unit of a multiprotein complex, which is part
      of the Wnt signaling pathway. In mice, a conditional homozygous beta-catenin
      knockout displays loss of neurons, impaired craniofacial development, and hair
      follicle defects, which is similar to the phenotype presented by the patient
      described in this clinical report. Thus, CTNNB1 haploinsufficiency causes
      neuronal loss, craniofacial anomalies and hair follicle defects in both humans
      and mice. Point mutations in CTNNB1 in human have recently been reported but this
      is the first observation of a new recognizable multiple congenital anomaly/mental
      retardation syndrome caused by CTNNB1 haploinsufficiency. This clinical report
      should prompt a search for point mutations in CTNNB1 in patients presenting
      developmental delay, mild hair, skin and facial anomalies, and neurodegeneration
      characterized by postnatal microcephaly, and progressive ataxia and spasticity.
      (c) 2014 Wiley Periodicals, Inc.

PMID- 24668551
TI  - A proteomic analysis of excreted and circulating proteins from obese patients
      following two different weight-loss strategies.
AB  - Bariatric surgery is the most successful therapeutic approach to weight loss, but
      how it leads to weight loss, and how it resolves obesity-related complications,
      including type-2 diabetes, are poorly understood. This study, comprising two
      groups of individuals, one on a low-calorie diet (n = 5) and one undergoing
      bariatric surgery (n = 7), used both targeted and untargeted proteomic approaches
      to determine changes in protein levels pre- and post-intervention (i.e. 3-6
      months later). Changes were observed in both circulating and excreted proteins
      following weight loss. Targeted multiplexed biochip arrays measured 12 plasma
      peptides/proteins involved in metabolism and inflammation: C-peptide, ferritin,
      interleukin-6, interleukin-1 alpha, resistin, insulin, tumor necrosis factor
      alpha, leptin, plasminogen-activator inhibitor-1, adiponectin, cystatin C, and C
      reactive protein. Following a low-calorie diet, plasma insulin and C-reactive
      protein levels were significantly reduced (P = 0.045 and P = 0.030,
      respectively); adiponectin increased and leptin decreased following surgery (P =
      0.014 and P = 0.005, respectively). Untargeted proteomic analysis employing 2D
      difference in-gel electrophoresis (DIGE) showed 28 protein spots with >=1.5-fold
      changes in expression following weight loss by a low-calorie diet; comparison of
      pre- and post-intervention urine samples from the bariatric surgery group showed
      changes in excretion of 110 protein spots. The combination of targeted protein
      analysis by multiplexed arrays and an exploratory (i.e. an unbiased or discovery)
      proteomic assessment of hundreds of proteins offers valuable insights into the
      mechanistic differences between alternative weight-loss strategies. This is a
      powerful hypothesis-generating approach to study complex, multifactorial
      syndromes such as obesity. The findings that arise from these studies can then be
      validated in targeted, hypothesis-directed investigations.

PMID- 24668552
TI  - Optimizing anesthetic regimen for surgery in mice through minimization of
      hemodynamic, metabolic, and inflammatory perturbations.
AB  - The role of anesthetics in animal research models is crucial, yet often ignored,
      and is almost never the primary focus of examination. Here, we investigated the
      impact of anesthetic regimens on different parameters of hemodynamics (blood
      pressure (BP) and heart rate (HR)), metabolism (glucose, insulin, and free fatty
      acids (FFA)), and inflammation (IL-6 and TNF-alpha) in two frequently used mouse
      strains (C57BL/6 and FVB). All animals were at a similar surgical plane of
      anesthesia, mechanically ventilated, and monitored for 60 min. The following
      anesthetic regimens were studied: (1) fentanyl-ketamine-midazolam (FKM), (2)
      fentanyl-midazolam-haldol (FMH), (3) pentobarbital (P), (4) fentanyl-fluanisone
      midazolam (FFM), (5) fentanyl-midazolam-acepromazine (FMA), (6) ketamine
      medetomidine-atropine (KMA), (7) isoflurane (ISO), and (8) propofol-fentanyl
      midazolam (PFM). Metabolic and inflammatory parameters were compared with those
      obtained from non-anesthetized animals. Hemodynamics: BP >80 mm Hg were only
      obtained with KMA, whereas hypotension (BP <60 mm Hg) was observed with FKM and
      P. HR >500 beats/min was observed with ISO and PFM, whereas HR <400 beats/min was
      induced with KMA, FMH (BL/6), P (BL/6), and FKM (FVB). Metabolism: Glucose and
      insulin were most disturbed by KMA and ISO and mildly disturbed by FMA, whereas
      FFM, PFM, and P did not have any effect. FFA increased largely by FMA, with ISO
      and FKM having no effects. Inflammation: Cytokines were increased least with
      ISO/FFM/FMA, whereas FKM and KMA induced the largest increases in cytokines. When
      aiming at achieving surgical anesthesia without large disturbances in
      hemodynamic, metabolic, and inflammatory profiles, FFM, ISO, or PFM may be the
      most neutral anesthetic regimens in mice.

PMID- 24668553
TI  - Intermittent hypoxia stimulates formation of binuclear neurons in brain cortex- a
      role of cell fusion in neuroprotection?
AB  - Oligodendrocyte fusion with neurons in the brain cortex is a part of normal
      ontogenesis and is a possible means of neuroregeneration. Following such fusion,
      the oligodendrocyte nucleus undergoes neuron-specific reprogramming, resulting in
      the formation of binuclear neurons, which doubles the functional capability of
      the neuron. In this study, we tested the hypothesis that the formation of
      binuclear neurons is involved in long-term adaptation of the brain to
      intermittent hypobaric hypoxia, which is known to be neuroprotective. Rats were
      adapted to hypoxia in an altitude chamber at a simulated altitude of 4000 m above
      sea level for 14 days (30 min increasing to 4 h, daily). One micrometer sections
      of the left motor cortex were analyzed by light microscopy. Phases of the fusion
      and reprogramming process were recorded, and the number of binuclear neurons was
      counted for all section areas containing pyramidal neurons of layers III-V. For
      the control group subjected to sham hypoxia, the density of binuclear neurons was
      4.49 +/- 0.32 mm(2). In the hypoxia-adapted group, this density increased to 5.71
      +/- 0.39 mm(2) (P < 0.04). In a subgroup of rats exposed to only one hypoxia
      session, the number of binuclear neurons did not differ from the number observed
      in the control group. We suggest that the increased content of binuclear neurons
      may serve as a structural basis for the neuroprotective effects of the adaptation
      to hypoxia.

PMID- 24668554
TI  - Characterization of inflammatory response induced by Potamotrygon motoro stingray
      venom in mice.
AB  - Freshwater stingray accidents cause intense pain followed by edema, erythema, and
      necrosis formation. Treatment for stingray envenomation is based on
      administration of analgesic, antipyretic, and anti-inflammatory drugs. This
      report evaluated the local inflammatory reaction-including edema formation,
      leukocyte recruitment, release of inflammatory mediators, and histopathological
      changes-after the intraplantar injection of Potamotrygon motoro stingray venom in
      mice. Edema was observed as soon as 15 min after venom injection, peaking at 30
      min, and lasted up to 48 h. In addition, P. motoro venom increased neutrophil
      counts in the site of injection, at all time periods and venom doses analyzed.
      Increased eosinophil and lymphocyte counts were detected mainly at 24 h.
      Moreover, monocytes/macrophages were observed in large amounts at 24 and 48 h.
      Microscopically, the venom induced leukocyte migration to the injured tissue,
      edema, mast cell degranulation, angiogenesis, and epidermal damage. Inflammatory
      mediator release (IL-6, MCP-1 and KC) was detected as soon as 1 h after venom
      injection, and it increased significantly at 4 h. At 24 h, the venom induced only
      the production of MCP-1. These results show that this stingray venom evokes a
      complex inflammatory reaction, with rapid and persistent edema formation,
      leukocyte recruitment, and release of cytokines and chemokines.

PMID- 24668556
TI  - Molecular diagnosis in clinical parasitology: when and why?
AB  - Microscopic detection and morphological identification of parasites from clinical
      specimens are the gold standards for the laboratory diagnosis of parasitic
      infections. The limitations of such diagnostic assays include insufficient
      sensitivity and operator dependence. Immunoassays for parasitic antigens are not
      available for most parasitic infections and have not significantly improved the
      sensitivity of laboratory detection. Advances in molecular detection by nucleic
      acid amplification may improve the detection in asymptomatic infections with low
      parasitic burden. Rapidly accumulating genomic data on parasites allow the design
      of polymerase chain reaction (PCR) primers directed towards multi-copy gene
      targets, such as the ribosomal and mitochondrial genes, which further improve the
      sensitivity. Parasitic cell or its free circulating parasitic DNA can be shed
      from parasites into blood and excreta which may allow its detection without the
      whole parasite being present within the portion of clinical sample used for DNA
      extraction. Multiplex nucleic acid amplification technology allows the
      simultaneous detection of many parasitic species within a single clinical
      specimen. In addition to improved sensitivity, nucleic acid amplification with
      sequencing can help to differentiate different parasitic species at different
      stages with similar morphology, detect and speciate parasites from fixed
      histopathological sections and identify anti-parasitic drug resistance. The use
      of consensus primer and PCR sequencing may even help to identify novel parasitic
      species. The key limitation of molecular detection is the technological expertise
      and expense which are usually lacking in the field setting at highly endemic
      areas. However, such tests can be useful for screening important parasitic
      infections in asymptomatic patients, donors or recipients coming from endemic
      areas in the settings of transfusion service or tertiary institutions with
      transplantation service. Such tests can also be used for monitoring these
      recipients or highly immunosuppressed patients, so that early preemptive
      treatment can be given for reactivated parasitic infections while the parasitic
      burden is still low. 

PMID- 24668557
TI  - Black howler monkey (Alouatta pigra) activity, foraging and seed dispersal
      patterns in shaded cocoa plantations versus rainforest in southern Mexico.
AB  - Recent evidence has shown that primates worldwide use agroecosystems as temporary
      or permanent habitats. Detailed information on how these primates are using these
      systems is scant, and yet their role as seed dispersers is often implied. The
      main objective of this study was to compare the activity, foraging patterns and
      seed dispersal role of black howler monkeys (Alouatta pigra) inhabiting shaded
      cocoa plantations and rainforest in southern Chiapas, Mexico. We gathered data on
      three monkey groups living in shaded cocoa plantations and three groups living in
      rainforest, using focal sampling, and collecting fecal samples. General activity
      and foraging patterns were similar in both habitats, with the exception that
      monkeys in the cocoa habitat spent more time feeding on petioles. Monkeys in
      shaded cocoa plantations dispersed 51,369 seeds (4% were seeds >=3 mm width) of
      16 plant species. Monkeys in the rainforest dispersed 6,536 seeds (78% were seeds
      >=3 mm width) of 13 plant species. Our data suggest that the difference between
      habitats in the proportion of large versus small seeds dispersed reflects
      differences in fruit species abundance and availability in cocoa versus forest.
      Mean seed dispersal distances were statistically similar in both habitats (cocoa
      = 149 m, forest = 86 m). We conclude that the studied cocoa plantations provide
      all elements necessary to constitute a long-term permanent habitat for black
      howler monkeys. In turn, howler monkeys living in these plantations are able to
      maintain their functional role as seed dispersers for those native tree and liana
      species present within their areas of activities.

PMID- 24668555
TI  - Vitamin D, immune regulation, the microbiota, and inflammatory bowel disease.
AB  - The inflammatory bowel diseases are complex diseases caused by environmental,
      immunological, and genetic factors. Vitamin D status is low in patients with
      inflammatory bowel diseases, and experimental inflammatory bowel diseases are
      more severe in vitamin D-deficient or vitamin D receptor knockout animals.
      Vitamin D is beneficial in inflammatory bowel diseases because it regulates
      multiple checkpoints and processes essential for homeostasis in the gut. Vitamin
      D inhibits IFN-gamma and IL-17 production while inducing regulatory T cells. In
      addition, vitamin D regulates epithelial cell integrity, innate immune responses,
      and the composition of the gut microbiota. Overall, vitamin D regulates multiple
      pathways that maintain gastrointestinal homeostasis. The data support improving
      vitamin D status in patients with inflammatory bowel diseases. 

PMID- 24668558
TI  - Accession to the European Union--an opportunity and a challenge for health
      systems and public health.

PMID- 24668559
TI  - Prevalence of severe obstructive sleep apnea in pediatric adenotonsillectomy
      patients.
AB  - OBJECTIVES/HYPOTHESIS: To determine the prevalence of severe obstructive sleep
      apnea (OSA) in a pediatric population who underwent indicated surgery for sleep
      disordered breathing (SDB). STUDY DESIGN: Retrospective chart review. METHODS: We
      reviewed the charts of patients aged 2 to 18 years who underwent tonsillectomy or
      adenotonsillectomy over a 4-year period. Indications for preoperative
      polysomnography (PSG), PSG results, and perioperative complications were
      recorded. RESULTS: Two hundred and thirty-five patients were included in the
      final analysis. Of these, 160 patients had preoperative PSG performed. The
      overall prevalence of severe OSA was 38%. The prevalence in patients for whom
      preoperative PSG was indicated or for which it should have been advocated
      according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO
      HNS) clinical practice guideline was 45% and 40%, respectively, whereas the
      prevalence in patients with no indication for preoperative PSG was 34%. There was
      no significant difference between groups (P = 0.39). The overall complication
      rate was 11%, with the rate being significantly lower (P = 0.0022) in patients
      who did not have preoperative PSG performed (0%) when compared to those who did
      (16%). CONCLUSIONS: The prevalence of severe OSA in this pediatric population was
      high. Specifically, a significant percentage of children who would not have
      received preoperative PSG under the AAO-HNS recommendations had severe OSA and
      were consequently admitted for overnight observation. Our results suggest that
      preoperative PSG should be obtained for all pediatric patients with sleep
      disordered breathing.

PMID- 24668560
TI  - Second antibody modeling assessment (AMA-II).
AB  - To assess the state of the art in antibody 3D modeling, 11 unpublished high
      resolution x-ray Fab crystal structures from diverse species and covering a wide
      range of antigen-binding site conformations were used as a benchmark to compare
      Fv models generated by seven structure prediction methodologies. The participants
      included: Accerlys Inc, Chemical Computer Group (CCG), Schrodinger, Jeff Gray's
      lab at John Hopkins University, Macromoltek, Astellas Pharma/Osaka University and
      Prediction of ImmunoGlobulin Structure (PIGS). The sequences of benchmark
      structures were submitted to the modelers and PIGS, and a set of models were
      generated for each structure. We provide here an overview of the organization,
      participants and main results of this second antibody modeling assessment (AMA
      II). Also, we compare the results with the first antibody assessment published in
      this journal (Almagro et al., 2011;79:3050).

PMID- 24668561
TI  - Hysteretic spin crossover above room temperature and magnetic coupling in
      trinuclear transition-metal complexes with anionic 1,2,4-triazole ligands.
AB  - The reaction of 4-(1,2,4-triazol-4-yl)ethanesulfonate (L) with Zn(2+), Cu(2+),
      Ni(2+), Co(2+), and Fe(2+) gave a series of analogous neutral trinuclear
      complexes with the formula [M3(MU-L)6(H2O)6] (1-5). These compounds were
      characterized by single-crystal X-ray diffraction, thermogravimetry, and
      elemental analysis. The magnetic properties of compounds 2-5 were studied.
      Complexes 2-4 show weak antiferromagnetic superexchange, with J values of -0.33
      (2), -9.56 (3), and -4.50 cm(-1) (4) (exchange Hamiltonian H = -2 J (S1S2+S2S3)).
      Compound 5 shows two additional crystallographic phases (5 b and 5 c) that can be
      obtained by dehydration and/or thermal treatment. These three phases exhibit
      distinct magnetic behavior. The Fe(2+) centers in 5 are in high-spin (HS)
      configuration at room temperature, with the central one exhibiting a non
      cooperative gradual spin transition below 250 K with T1/2 = 150 K. In 5 b, the
      central Fe(2+) stays in its low-spin (LS) state at room temperature, and
      cooperative spin transition occurs at higher temperatures and with the appearance
      of memory effect (T1/2? = 357 K and T1/2? = 343 K). In the case of 5 c, all iron
      centers remain in their HS configuration down to very low temperatures, with weak
      antiferromagnetic coupling (J = -1.16 cm(-1)). Compound 5 b exhibits spin
      transition with memory effect at the highest temperature reported, which matches
      the remarkable features of coordination polymers.

PMID- 24668564
TI  - Breast cancer screening offers few benefits to women over 70, finds study.

PMID- 24668565
TI  - Isoprene-styrene chain shuttling copolymerization mediated by a lanthanide half
      sandwich complex and a lanthanidocene: straightforward access to a new type of
      thermoplastic elastomers.
AB  - A lanthanide half-sandwich complex and a ansa lanthanidocene have been assessed
      for isoprene-styrene chain shuttling copolymerization with n-butylethylmagnesium
      (BEM). In the presence of 1 equiv BEM, a fully amorphous multiblock
      microstructure of soft and hard segments is achieved. The microstructure consists
      of poly(isoprene-co-styrene) blocks, with hard blocks rich in styrene and soft
      blocks rich in isoprene. The composition of the blocks and the resulting glass
      transition temperatures (Tg ) can be easily modified by changing the feed and/or
      the relative amount of the catalysts, highlighting a new class of thermoplastic
      elastomers (TPEs) with tunable transition temperatures. The materials self
      organize into nanostructures in the solid state. 

PMID- 24668563
TI  - Elevated hyaluronan and hyaluronan-mediated motility receptor are associated with
      biochemical failure in patients with intermediate-grade prostate tumors.
AB  - BACKGROUND: The clinical course of prostate cancer (PCa) measured by biochemical
      failure (BF) after prostatectomy remains unpredictable in many patients,
      particularly in intermediate Gleason score (GS) 7 tumors, suggesting that
      identification of molecular mechanisms associated with aggressive PCa biology may
      be exploited for improved prognostication or therapy. Hyaluronan (HA) is a high
      molecular weight polyanionic carbohydrate produced by synthases (HAS1 through
      HAS3) and fragmented by oxidative/nitrosative stress and hyaluronidases (HYAL1
      through HYAL4, SPAM1) common in PCa microenvironments. HA and HA fragments
      interact with receptors CD44 and hyaluronan-mediated motility receptor (HMMR),
      resulting in increased tumor aggressiveness in experimental PCa models. This
      study evaluated the association of HA-related molecules with BF after
      prostatectomy in GS7 tumors. METHODS: Tissue microarrays were constructed from a
      96-patient cohort. HA histochemistry and HAS2, HYAL1, CD44, CD44v6, and HMMR
      immunohistochemistry were quantified using digital pathology techniques. RESULTS:
      HA in tumor-associated stroma and HMMR in malignant epithelium were significantly
      and marginally significantly associated with time to BF in univariate analysis,
      respectively. After adjusting for clinicopathologic features, both HA in tumor
      associated stroma and HMMR in malignant epithelium were significantly associated
      with time to BF. Although not significantly associated with BF, HAS2 and HYAL1
      positively correlated with HMMR in malignant epithelium. Cell culture assays
      demonstrated that HMMR bound native and fragmented HA, promoted HA uptake, and
      was required for a promigratory response to fragmented HA. CONCLUSIONS: HA and
      HMMR are factors associated with time to BF in GS7 tumors, suggesting that
      increased HA synthesis and fragmentation within the tumor microenvironment
      stimulates aggressive PCa behavior through HA-HMMR signaling.

PMID- 24668566
TI  - The association between parenting stress, parenting self-efficacy, and the
      clinical significance of child ADHD symptom change following behavior therapy.
AB  - We examined parenting stress (PST) and self-efficacy (PSE) following
      participation in behavioral parent training (BPT) with regard to child treatment
      response. Forty-three families of children diagnosed with ADHD participated in a
      modified BPT program. Change in PST and PSE was evaluated using a single group,
      within-subjects design. Parenting outcomes based on child treatment response were
      evaluated based upon (1) magnitude and (2) clinical significance of change in
      child symptom impairment. Parents reported significant improvements in stress and
      self-efficacy. Parents of children who demonstrated clinically significant
      reduction in ADHD symptoms reported lower stress and higher self-efficacy than
      those of children with continued impairments. Magnitude of child impairment was
      not associated with parent outcomes. Clinical implications for these results
      include extending treatment duration to provide more time for symptom
      amelioration and parent-focused objectives to improve coping and stress
      management. 

PMID- 24668567
TI  - Anxiety disorder symptoms in Chinese preschool children.
AB  - The present study investigated anxiety disorder symptoms in Chinese preschool
      children. A total of 1,854 mothers of children aged 3-6 years completed the 28
      item Chinese version of Spence Preschool Anxiety Scale (PAS). Results
      demonstrated that the structure of anxiety in Chinese preschool children included
      five factors, and this five-factor structure applied to different age and gender
      groups. Inconsistent with the study by Edwards et al. (J Clin Child Adolesc
      Psychol 39:400-409, 2010) suggesting that obsessive-compulsive disorder did not
      comprise an independent factor in Australian preschoolers, this symptom can be
      viewed as an independent factor in Chinese preschoolers. Younger children
      displayed higher anxiety levels than older children. Anxiety symptoms of Chinese
      preschoolers were found at a high level compared to other studies. Substantial
      differences were found with regard to the content of prevalent anxiety symptoms
      among Chinese and Australian preschool children. The applicability of the five
      factor structure of PAS and research implications are discussed.

PMID- 24668568
TI  - Rutin potentiates insulin receptor kinase to enhance insulin-dependent glucose
      transporter 4 translocation.
AB  - SCOPE: We investigated whether rutin, a flavonoid isolated from Toona sinensis
      Roem, has the ability to enhance insulin-dependent receptor kinase (IRK) activity
      and glucose transporter 4 (GLUT4) translocation in differentiated myotubes. We
      also tested the effects of rutin treatment in insulin-resistant mice using an
      oral glucose tolerance test (OGTT). METHODS AND RESULTS: Rutin potentiated
      insulin receptor kinase (IRK) phosphorylation when IRK autophosphorylation was
      triggered by insulin in differentiated myotubes. Co-treatment of cells with rutin
      and insulin attenuated S961-mediated inhibition of insulin-dependent GLUT4
      translocation. In S961-treated C57BL/6 mice, an in vivo model of insulin
      resistance and type 2 diabetes, rutin treatment showed a normoglycemic effect in
      the OGTT. CONCLUSION: This study shows evidence that rutin may serve as a
      potential agent for glycemic control through enhancement of IRK activity, thereby
      inducing the insulin signaling pathway causing increased GLUT4 translocation and
      increased glucose uptake.

PMID- 24668569
TI  - (1)H, (15)N and (13)C resonance assignments of the two TPR domains from the human
      RPAP3 protein.
AB  - We report the nearly complete (1)H, (15)N and (13)C resonance assignments of the
      two tetratricopeptide-repeat domains of the human RPAP3 protein, a co-chaperone
      of the heat-shock protein family. 

PMID- 24668571
TI  - Association of IL1beta and IL4 gene polymorphisms with nasal polyps in a Polish
      population.
AB  - Imbalance between proinflammatory and anti-inflammatory cytokines may regulate
      the inflammatory reaction in the nasal polyps. Polymorphisms in the regulatory
      regions of the cytokines genes may influence their expression. The aim of this
      study was to investigate the relationship between an IL-1beta and IL-4 promoter
      polymorphisms and nasal polyps. The C-511T promoter polymorphism of the IL-1beta
      gene and C-590T promoter polymorphism of the IL-4 gene were genotyped by
      polymerase chain reaction-restriction fragment length polymorphism analysis in
      208 Polish patients with nasal polyps and 200 healthy Polish subjects. The risk
      of susceptibility to NP was significantly higher in patients with NP who had -511
      T/T genotype of IL1beta than in controls (OR 3.07; 95 % CI 1.18-7.99). No
      statistically significant differences were found between NP patients and the
      control group with regard to genotype distribution and allele frequencies of C/T
      polymorphism of IL4 gene. Our study demonstrated that the TT genotype for C-511T
      mutation associated with the risk of developing NP in a Polish population. 

PMID- 24668570
TI  - No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to
      statin therapy in the Greek population.
AB  - Interindividual variability exists in statin lipid-lowering response, partially
      attributed to genetic factors. Organic anion-transporting polypeptide 1B1
      (OATP1B1) encoded by SLCO1B1 gene (solute carrier organic anion transporter
      family member 1B1) facilitates hepatic uptake of simvastatin and atorvastatin.
      SLCO1B1 polymorphisms are strongly associated with statin-induced myopathy
      whereas few studies have assessed their effect on statin differential response.
      In the present study, we analyzed the association of SLCO1B1 521T>C, 388A>G and
      411G>A polymorphisms with response to atorvastatin and simvastatin in 386 adults
      (201 atorvastatin-treated and 185 simvastatin-treated) with primary
      hypercholesterolemia, all of Greek origin. Total cholesterol and low-density
      lipoprotein cholesterol were measured at baseline and on 6 months of treatment.
      Genetic polymorphisms were analyzed by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. A novel RFLP protocol was
      developed for the simultaneous identification of 388A>G and 411G>A polymorphisms.
      SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms were not associated with lipid
      lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene
      interaction was observed on the effect of the analyzed SLCO1B1 polymorphisms in
      statin lipid lowering response in either statin-treated patient cohort. Further
      studies in different populations are required to draw firm conclusion on the
      potential association of SLCO1B1 polymorphisms with statin lipid-lowering
      response.

PMID- 24668573
TI  - Abuse potential of carbamazepine for euphorigenic effects.
AB  - Euphoric effects following administration of CBZ alone have been never reported
      in any international journals and this is the first case report regarding to
      potential abuse of CBZ for euphoria. We hope this report will be a warning to
      physicians who will decide to prescribe CBZ, particularly in the patients who had
      a history of alcohol dependence as abuse potential of CBZ for euphoric effects
      has been frequently reported in the treatment of alcohol withdrawal. 

PMID- 24668572
TI  - Interval training intensity affects energy intake compensation in obese men.
AB  - PURPOSE: Compensatory responses may attenuate the effectiveness of exercise
      training in weight management. The aim of this study was to compare the effect of
      moderate- and high-intensity interval training on eating behavior compensation.
      METHODS: Using a crossover design, 10 overweight and obese men participated in 4
      week moderate (MIIT) and high (HIIT) intensity interval training. MIIT consisted
      of 5-min cycling stages at +/- 20% of mechanical work at 45%VO(2)peak, and HIIT
      consisted of alternate 30-s work at 90%VO(2)peak and 30-s rests, for 30 to 45
      min. Assessments included a constant-load exercise test at 45%VO(2)peak for 45
      min followed by 60-min recovery. Appetite sensations were measured during the
      exercise test using a Visual Analog Scale. Food preferences (liking and wanting)
      were assessed using a computer-based paradigm, and this paradigm uses 20
      photographic food stimuli varying along two dimensions, fat (high or low) and
      taste (sweet or nonsweet). An ad libitum test meal was provided after the
      constant-load exercise test. RESULTS: Exercise-induced hunger and desire to eat
      decreased after HIIT, and the difference between MIIT and HIIT in desire to eat
      approached significance (p = .07). Exercise-induced liking for high-fat nonsweet
      food tended to increase after MIIT and decreased after HIIT (p = .09). Fat intake
      decreased by 16% after HIIT, and increased by 38% after MIIT, with the difference
      between MIIT and HIIT approaching significance (p = .07). CONCLUSIONS: This study
      provides evidence that energy intake compensation differs between MIIT and HIIT.

PMID- 24668574
TI  - Fluid resuscitation and standard drug treatment strategies in heatstroke Chinese
      patients.
AB  - The objective of the present study was to evaluate different stage fluid and
      standard drug treatment strategies in 47 heatstroke patients. 47 adults with
      Heatstroke received fluid resuscitation treatment guided by transpulmonary
      thermodilution (PiCCO) in our intensive care unit. Systemic hemodynamics,
      microvascular indices and measures of acidosis, renal function, and pulmonary
      edema were followed prospectively. The speed of recovery and the component change
      was compared during the 6 h, 48 h and 96 h after the 3 stage fluid therapy. All
      patients were hyperpyrexia (core temperature>41 degrees C), and on ventilation
      when enrolled in the ICU. Patients received a 6.17 (+/-1.8) ml/kg/h of crystal
      fluid and 3.31 (+/-0.5) ml/kg/h of colloidal fluid in the first 6 h; (3.41+/-1.2)
      ml/kg/h crystal fluid along with 2.27 (+/-0.3) ml/kg/h colloidal fluid in the
      first 48 h; 2.27 (+/-0.6) ml/kg/h crystal fluid along with 2.06 (+/-0.3) ml/kg/h
      colloidal fluid in the next 48 h. With resuscitation, acid-base status
      deteriorated in 25 of 47 patients (53.1%), extravascular lung water increased in
      36 of 47 resuscitated patients (77%); 21 of these patients developed pulmonary
      edema though guided by transpulmonary thermodilution, 30 (63.8%) patients
      survived. All patients with pulmonary edema during the study were hypovolemic or
      euvolemic at the time pulmonary edema developed. Plasma lactate was lower in
      hypovolemic patients before (p<0.05) and after (p<0.05) resuscitation. Acute
      kidney injury was evident in 21 of 47 patients (47%) 48 h after enrollment. In
      conclusion, our study revealed that fluid resuscitation post heatstroke should be
      adjusted according to different stages.

PMID- 24668575
TI  - ED50 and ED95 of intrathecal isobaric levobupivacaine coadministered with
      fentanyl for transurethral resections: randomized, double-blind trial.
AB  - BACKGROUND: Levobupivacaine use is progressively increased for intrathecal
      anesthesia in transurethral resections. The aim was to determine ED(50) and
      ED(95) of intrathecal isobaric levobupivacaine by addition of 25 mcg fentanyl for
      patients undergoing transurethral resections. METHODS: A total of 100 patients
      undergoing transurethral resections with ASA I-III, were randomized to groups
      receiving intrathecal 0.5% isobaric levobupivacaine in doses of 6, 8, 10, 12 or
      14 mg in equal volumes with 25 mcg intrathecal fentanyl addition. Sensorial block
      level was determined by pinprick and motor block by Bromage scale. RESULTS: Mean
      onset time of sensorial block in 6 mg group was significantly longer than that of
      sensorial block in 10 mg, 12 mg and 14 mg groups (p<0.01), 8 mg was longer than
      12 mg and 14 mg (p<0.01), and 10 mg onset time of sensorial block was
      significantly longer than 12 mg and 14 mg (p<0.01). Mean onset time of T10
      sensory level in 6 mg group was significantly longer than mean onset time of T10
      sensory level in 10 mg, 12 mg and 14 mg (p<0.01), the mean onset time of T10
      sensory level in 8 mg group was also significantly longer than that of 12 mg, 14
      mg groups (p<0.01). ED(50) and ED(95) of levobupivacaine coadministered with 25
      mcg fentanyl were 7.32 mg and 10.88 mg, respectively. CONCLUSION: Levobupivacaine
      with opioid co-administration can be used in doses considerably lower than doses
      proposed for routine use as it is a safe drug depending on its hemodynamic
      effects, side effects.

PMID- 24668576
TI  - Investigation of the memory impairment in rats fed with oxidized-cholesterol-rich
      diet employing passive avoidance test.
AB  - BACKGROUND: Recent studies have shown that hypercholesterolemia, besides being a
      risk factor for cardiovascular diseases, has also toxic effects on central
      nervous system. The design of the present study was to investigate the effects of
      dietary cholesterol and oxidized cholesterol on cognitive function. METHODS: Male
      Wistar rats were randomly divided into 3 groups. The animals were fed with three
      normal, 2% cholesterol-rich, and 2% oxidized cholesterol-rich diets for 14 weeks.
      Memory impairment was analyzed by passive avoidance test. Coenzyme Q10 content
      was also measured by a validate RP-HPLC method. Besides, lipid peroxidation in
      serum and brain tissue was determined by malondialdehyde concentration
      measurement. RESULTS: The results showed that feeding rats with high oxidized
      cholesterol diet for 14 weeks significantly impaired the cognitive function
      compared to the normal (P<0.001) and high cholesterol-fed groups (P<0.01). The
      memory impairment was positively correlated to the serum level of the oxidized
      LDL; it was significantly associated with the increased malondialdehyde
      concentration on the brain tissue of both groups (P<0.05 and P<0.001,
      respectively). The total antioxidant level in the serum was also decreased in
      rats fed with the oxidized cholesterol (P<0.05). Moreover, the brain coenzyme Q10
      content was significantly declined in the animals fed with the oxidized
      cholesterol-rich diet compared to the animals fed with the normal (P<0.01) and
      cholesterol-rich diets (P<0.05). CONCLUSION: The results suggested that the high
      dietary intake of the oxidized-cholesterol might impair the memory that could be
      correlated to the oxidative stress and declined the coenzyme Q10 content of the
      brain tissue.

PMID- 24668577
TI  - Protective Effects of Melatonin against Cyclophosphamide-induced Oxidative Lung
      Toxicity in Mice.
AB  - This study was undertaken to evaluate the protective effects of melatonin against
      cyclophosphamide (CP)-induced oxidative lung toxicity in mice. Mice were pre
      treated with various doses of melatonin for 7 consecutive days and were then
      injected with CP (200 mg/kg b. w.) 1 h after last melatonin injection. After 24
      h, the mice were euthanized and their lungs were immediately harvested. Several
      biomarkers associated with oxidative stress in lung homogenates, such as
      thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH)
      levels and the activity of superoxide dismutase (SOD) and catalase (CAT) were
      measured spectrophotometrically. A single dose of CP markedly altered the levels
      of these oxidative stress biomarkers in lung homogenates. However, increased
      lipid peroxidation, measured as TBARs, was significantly inhibited in the lung
      tissues of the melatonin-pretreated mice compared to the CP alone-injected group.
      In addition, pretreatment with melatonin also significantly restored GSH levels
      and SOD and CAT activities. Melatonin also effectively protected animals from CP
      induced histological abnormalities in lung tissue. In conclusion, the increase in
      oxidative stress markers and concomitant adaptations by the antioxidant defense
      system indicates that oxidative stress plays an important role in CP-induced
      damage to the lung. Moreover, melatonin is a potent natural antioxidant that
      helps prevent CP-induced oxidative toxicity in mouse lung tissues. Thus, because
      melatonin is regarded to be a safe pineal secretory product, it may be used
      concomitantly as a supplement to reduce lung damage in patients undergoing
      chemotherapy.

PMID- 24668578
TI  - Effects of Teratogenic Drugs on CYP1A1 Activity in Differentiating Rat Embryo
      Cells.
AB  - CYP1A1, a P450 isoenzyme, is involved in the phase I xenobiotic metabolism
      including teratogen drugs. In the present study, the ability of teratogens to
      elevate the embryonic expression of CYP1A1 was examined. Micromass cell cultures
      prepared from day 13 rat embryo limb buds (LB). LB cells were cultivated and
      exposed for 5 days to retinoic acid (RA), hydrocortisone (HC), caffeine (CA) and
      quinine (QN). CYP1A1 protein expression and activity were measured using
      immunofluorescence staining and ethoxyresorufin O-deethylation (EROD) assay,
      respectively. The EROD activity increased significantly following LB cells
      exposure to RA and HC (p<0.05) but the expression of CYP1A1 protein was reduced
      by these drugs, whereas the expression of CYP1A1 protein and EROD activity
      decreased significantly following the addition of CA and QN (p<0.05, p<0.01). Our
      findings show that studied teratogens have potency to increase CYP1A1 activity. 

PMID- 24668579
TI  - Regional management of farmland feeding geese using an ecological prioritization
      tool.
AB  - Wild geese foraging on farmland cause increasing conflicts with agricultural
      interests, calling for a strategic approach to mitigation. In central Norway,
      conflicts between farmers and spring-staging pink-footed geese feeding on
      pastures have escalated. To alleviate the conflict, a scheme by which farmers are
      subsidized to allow geese to forage undisturbed was introduced. To guide
      allocation of subsidies, an ecological-based ranking of fields at a regional
      level was recommended and applied. Here we evaluate the scheme. On average, 40 %
      of subsidized fields were in the top 5 % of the ranking, and 80 % were within the
      top 20 %. Goose grazing pressure on subsidized pastures was 13 times higher
      compared to a stratified random selection of non-subsidized pastures, capturing
      67 % of the pasture feeding geese despite that subsidized fields only comprised
      13 % of the grassland area. Close dialogue between scientists and managers is
      regarded as a key to the success of the scheme.

PMID- 24668580
TI  - The use and effectiveness of rituximab maintenance in patients with follicular
      lymphoma diagnosed between 2004 and 2007 in the United States.
AB  - BACKGROUND: The authors examined the "real-world" effectiveness of rituximab (R)
      maintenance therapy (R-maintenance) compared with observation after R-based
      induction therapy in patients with previously untreated follicular lymphoma (FL)
      in the United States. METHODS: The National LymphoCare Study is a prospective,
      multicenter, observational study that enrolled > 2700 untreated patients with FL
      diagnosed from 2004 to 2007 at 265 sites in the United States. Among these,
      patients who achieved at least stable disease after R-based induction therapy
      were eligible for the current analysis. Patients who initiated R-maintenance
      within 215 days of completing induction therapy were categorized as the R
      maintenance group, and those who did not initiate therapy during this period were
      categorized as the observation group. The objective of the current study was to
      determine the effect of R-maintenance on progression-free survival (PFS), time to
      next treatment (TTNT), and overall survival (OS). RESULTS: A total of 1439
      patients completed R-based induction therapy, 1186 of whom met all inclusion
      criteria (541 patients received R-maintenance and 645 patients were observed).
      Characteristics that were found to be predictive of receiving R-maintenance were
      histology grade (1/2), Ann Arbor stage of disease (III/IV), geographic region
      (region other than the West), and practice setting (community practice). With a
      median follow-up of 5.7 years, R-maintenance was associated with superior PFS
      (hazards ratio [HR], 0.68; 95% confidence interval [95% CI], 0.56-0.84 [P =
      .0003]) and TTNT (HR, 0.66; 95% CI, 0.52-0.84 [P = .0007]). No significant
      difference in OS was observed (HR, 0.81; 95% CI, 0.58-1.14 [P = .23]).
      CONCLUSIONS: R-maintenance in patients with FL and at least stable disease after
      R-based induction therapy provided significantly longer PFS and TTNT in
      comparison with observation, but no significant difference in OS was observed
      with 5-years of follow-up. This comparative effectiveness study aligns with the
      results of randomized trials suggesting that similar outcomes occur with R
      maintenance in FL with the treatment variations observed in clinical practice.

PMID- 24668582
TI  - Testing problem-solving capacities: differences between individual testing and
      social group setting.
AB  - Testing animals individually in problem-solving tasks limits distractions of the
      subjects during the test, so that they can fully concentrate on the problem.
      However, such individual performance may not indicate the problem-solving
      capacity that is commonly employed in the wild when individuals are faced with a
      novel problem in their social groups, where the presence of a conspecific
      influences an individual's behaviour. To assess the validity of data gathered
      from parrots when tested individually, we compared the performance on patterned
      string tasks among parrots tested singly and parrots tested in social context. We
      tested two captive groups of orange-winged amazons (Amazona amazonica) with
      several patterned-string tasks. Despite the differences in the testing
      environment (singly vs. social context), parrots from both groups performed
      similarly. However, we found that the willingness to participate in the tasks was
      significantly higher for the individuals tested in social context. The study
      provides further evidence for the crucial influence of social context on
      individual's response to a challenging situation such as a problem-solving test. 

PMID- 24668581
TI  - Clinical significance of primary tumor resection in colorectal cancer patients
      with synchronous unresectable metastasis.
AB  - BACKGROUND: The aim of this study was to compare the outcomes in colorectal
      cancer (CRC) patients with synchronous unresectable metastases who received
      either primary tumor resection (PTR) or chemotherapy as the first treatment and
      to investigate the clinical course of asymptomatic patients who received
      chemotherapy as the first treatment. METHODS: We retrospectively analyzed 324 CRC
      patients with synchronous unresectable metastases. Overall survival (OS) was
      analyzed for the two groups (upfront PTR group [n = 72] vs. upfront chemotherapy
      group [n = 252]). Surgical morbidity and mortality were recorded. In the
      asymptomatic patients who received upfront chemotherapy, the incidences of
      primary tumor-related complications were analyzed. RESULTS: In patients who
      underwent PTR as the first treatment, the median OS period was superior to those
      who received upfront chemotherapy (17.2 vs. 13.6 months, P = 0.002). In the PTR
      group, surgical morbidity and mortality were 11.6% and 1.9%, respectively. Of the
      252 asymptomatic patients, the incidence of primary tumor-related complications
      was 35%. Emergent surgery was ultimately done in 14% of the 252 patients.
      CONCLUSION: CRC patients with synchronous unresectable metastases who underwent
      PTR followed by chemotherapy had significantly longer survival times compared to
      patients who received chemotherapy as the first treatment.

PMID- 24668583
TI  - Finding a voice: participatory research with street-involved youth in the youth
      injection prevention project.
AB  - This article uses a Positive Youth Development framework to explore the
      experiences of six experiential youth coresearchers (YCs) in the Youth Injection
      Prevention (YIP) participatory research project, and the parallel track process
      of empowerment and capacity building that developed. The YIP project was
      conducted in Metro Vancouver at the BC Centre for Disease Control and community
      organizations serving street-involved youth. A process evaluation was conducted
      to explore themes in the YCs experience in the project, as well as process
      strengths and challenges. Semistructured interviews with the YCs, researcher
      field notes, and team meeting and debrief session minutes were analyzed. The YIP
      project appears to have exerted a positive influence on the YCs. Positive self
      identities, sense of purpose, reconceptualization of intellectual ability, new
      knowledge and skills, supportive relationships, finding a voice, and social and
      self-awareness were among the positive impacts. Process strengths included team
      building activities, team check-in and checkout sessions, and professional
      networking opportunities. Process challenges included the time required to help
      YCs overcome personal barriers to participation. The YIP project demonstrates
      that participatory research with street-involved youth is a viable research
      option that contributes to positive youth development and empowerment. 

PMID- 24668584
TI  - Cooperative effect of two metals: CoPd(OAc)4-catalyzed C-H amination and
      aziridination.
AB  - The first Co/Pd-cocatalyzed intramolecular C-H amination and aziridination
      reactions were developed. Sulfamate esters were converted to oxathiazinanes by
      using CoPd(OAc)4 as catalyst and PhI(OAc)2 as oxidant. The mutual presence of
      both Co and Pd is crucial for the catalytic activity. This combination of two
      metals with simple acetate ligands provides an economical alternative to the Rh
      catalyzed insertion of nitrenoids into C-H bonds.

PMID- 24668585
TI  - Whole genome sequencing identifies a novel occludin mutation in microcephaly with
      band-like calcification and polymicrogyria that extends the phenotypic spectrum.

PMID- 24668586
TI  - Catalytic transfer hydrogenation by a trivalent phosphorus compound: phosphorus
      ligand cooperation pathway or P(III) /P(V) redox pathway?
AB  - Main-group-element catalysts are a desirable alternative to transition-metal
      catalysts because of natural abundance and cost. However, the examples are very
      limited. Catalytic cycles involving a redox process and E-ligand cooperation
      (E=main-group element), which are often found in catalytic cycles of transition
      metal catalysts, have not been reported. Herein theoretical investigations of a
      catalytic hydrogenation of azobenzene with ammonia-borane using a trivalent
      phosphorus compound, which was experimentally proposed to occur through P(III)
      /P(V) redox processes via an unusual pentavalent dihydridophosphorane, were
      performed. DFT and ONIOM(CCSD(T):MP2) calculations disclosed that this catalytic
      reaction occurs through a P-O cooperation mechanism, which resembles the metal
      ligand cooperation mechanism of transition-metal catalysts. 

PMID- 24668587
TI  - Evaluation of benzothiophene carboxamides as analgesics and anti-inflammatory
      agents.
AB  - Nonsteroid anti-inflammatory drugs (NSAIDs) represent standard therapy for the
      alleviation of pain and inflammation. At present various classes of compounds
      have been reported as selective inhibitors of cyclooxygenase-2 (COX-2). However,
      they are associated with adverse side effects. To address these issues, we report
      here a new class of compounds that exhibit potent analgesic and anti-inflammatory
      response. Substituted bromo-benzothiophene carboxamides (4-11) were examined for
      their analgesic and anti-inflammatory properties. Our findings demonstrate that
      newly synthesized bromo-benzothiophene carboxamide derivatives 4, 6, and 8
      attenuate nociception and inflammation at lower concentration than classical
      NSAIDs, such as ibuprofen. These compounds act by selectively inhibiting COX-2
      and by disrupting the prostaglandin-E2-dependent positive feedback of COX-2
      regulation, which was further substantiated by reduction in the levels of
      cytokines, chemokines, neutrophil accumulation, synthesis of prostaglandin-E2,
      expression of COX-2, and neutrophil activation at lower concentration than the
      classic NSAID ibuprofen. Toxicological study reveals that these compounds are
      well tolerated and metabolized to avoid any toxicity. Thus, these molecules
      represent a new class of analgesic and anti-inflammatory agents. (c) 2014 IUBMB
      Life, 66(3):201-211, 2014.

PMID- 24668589
TI  - The influenza fusion peptide promotes lipid polar head intrusion through hydrogen
      bonding with phosphates and N-terminal membrane insertion depth.
AB  - Influenza infection requires fusion between the virus envelope and a host cell
      endosomal membrane. The influenza hemagglutinin fusion peptide (FP) is essential
      to viral membrane fusion. It was recently proposed that FPs would fuse membranes
      by increasing lipid tail protrusion, a membrane fusion transition state. The
      details of how FPs induce lipid tail protrusion, however, remain to be
      elucidated. To decipher the molecular mechanism by which FPs promote lipid tail
      protrusion, we performed molecular dynamics simulations of the wild-type (WT) FP,
      fusogenic mutant F9A, and nonfusogenic mutant W14A in model bilayers. This
      article presents the peptide-lipid interaction responsible for lipid tail
      protrusion and a related lipid perturbation, polar head intrusion, where polar
      heads are sunk under the membrane surface. The backbone amides from the four N
      terminal peptide residues, deeply inserted in the membrane, promoted both
      perturbations through H bonding with lipid phosphates. Polar head intrusion
      correlated with peptides N-terminal insertion depth and activity: the N-termini
      of WT and F9A were inserted deeper into the membrane than nonfusogenic W14A.
      Based on these results, we propose that FP-induced polar head intrusion would
      complement lipid tail protrusion in catalyzing membrane fusion by reducing
      repulsions between juxtaposed membranes headgroups. The presented model provides
      a framework for further research on membrane fusion and influenza antivirals.

PMID- 24668590
TI  - The computational road to better catalysts.
AB  - Computational studies, especially those that use density functional theory (DFT),
      have become pervasive in the characterization, mechanistic study, and
      optimization of homogeneous organometallic catalysts, and the "rational" design
      of such catalysts seems within reach once more. But how advanced, user-friendly,
      and reliable are the computational tools that are currently available? Here we
      summarize the current state of the art for predictive computational
      organometallic chemistry in reference to the different stages of catalyst
      development by considering characterization, mechanistic studies, fine
      tuning/optimization, and evaluation of novel designs. We also assess critically
      where the strengths and weaknesses of computational studies lie and hence map out
      the road ahead for the design and discovery of novel catalysts in silico and in
      combination with targeted experimental studies. 

PMID- 24668591
TI  - Mastectomy rates for ductal carcinoma in situ vary widely in UK, audit shows.

PMID- 24668592
TI  - Quantitative analysis of progressive removal of nasal structures during
      endoscopic suprasellar approach.
AB  - OBJECTIVES/HYPOTHESIS: Following recent studies measuring working area and
      surgical freedom of transcranial approaches, we aimed to quantify the gain
      achieved with progressive removal of nasal structures during the endoscopic
      endonasal suprasellar approach. STUDY DESIGN: Human cadaveric anatomic study.
      METHODS: The width of the endoscopic endonasal corridor to the suprasellar area
      was obtained and measured in five cadaver heads using a computerized tracking
      system with six steps: 1) standard approach with monolateral lateralization of
      middle turbinate; 2) standard bilateral lateralization of the middle turbinates;
      3) monolateral middle turbinectomy; 4) bilateral middle turbinectomy; 5)
      monolateral ethmoidectomy; 6) bilateral ethmoidectomy. RESULTS: The progressive
      removal of nasal structures offers a nonlinear increasing of the working area
      during the first steps of the procedure. The maximum advantage is offered by
      bilateral lateralization of the middle turbinates (102.7% increase in exposure),
      whereas a moderate increase is observed with each following step. Surgical
      freedom mainly increased during the first part of the approach, that is, with a
      monolateral right middle turbinectomy (17.9% raise of maneuverability), whereas
      additional steps did not increase surgical freedom enough to justify an
      aggressive nasal disruption. CONCLUSIONS: Monolateral turbinectomy on the side of
      endoscope docking represents the best solution, optimizing working area and
      surgical freedom (offering increases of 116.9% and 17.9%, respectively).
      Bilateral turbinectomy, together with a monolateral anterior and posterior
      ethmoidectomy, can be reserved for selected cases (increases of 148.5% and 24.7%,
      respectively). Bilateral ethmoidectomy does not significantly improve surgical
      freedom (0.81%). LEVEL OF EVIDENCE: N/A. Laryngoscope 124:2231-2237, 2014.

PMID- 24668593
TI  - Follicular dendritic cell sarcoma of parapharyngeal space: a case report and
      review of the literature.
AB  - Follicular dendritic cell sarcoma (FDCS) of the parapharyngeal space is a rare
      malignant tumor. Only eleven cases of FDCS of the parapharyngeal space have been
      reported in English literature. Most of the reported cases developed tumor
      recurrence within 1 year or had metastasis. Because of the rarity of FDCS in the
      parapharyngeal space and peculiar histology, it can be misdiagnosed as
      undifferentiated carcinoma or meningioma. Therefore, pathologists should be aware
      of the existence of FDCS in this location. This paper aims to report a unique
      case of FDCS of the parapharyngeal space without recurrence in 26 months follow
      up with a review of the literature.

PMID- 24668595
TI  - Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong
      associations between hyaline and calcified cartilage abnormalities.
AB  - Osteochondral lesions in the joints of the distal tarsal region of young
      Icelandic horses provide a natural model for the early stages of osteoarthritis
      (OA) in low-motion joints. We describe and characterise mineralised and non
      mineralised osteochondral lesions in left distal tarsal region joint specimens
      from twenty-two 30 +/-1 month-old Icelandic horses. Combinations of confocal
      scanning light microscopy, backscattered electron scanning electron microscopy
      (including, importantly, iodine staining) and three-dimensional microcomputed
      tomography were used on specimens obtained with guidance from clinical imaging.
      Lesion-types were described and classified into groups according to morphological
      features. Their locations in the hyaline articular cartilage (HAC), articular
      calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues
      were identified and their frequency in the joints recorded. Associations and
      correlations between lesion-types were investigated for centrodistal joints only.
      In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation,
      HAC central chondrocyte clusters, ACC arrest and ACC advance had significant
      associations and strong correlations. These lesion-types had moderate to high
      frequency in centrodistal joints but low frequencies in tarsometatarsal and
      talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant
      associations with other lesion-types in the centrodistal joints but high
      frequency in both the centrodistal and tarsometatarsal joints. The frequency of
      SCB lesion-types in all joints was low. Hypermineralised infill phase lesion
      types were detected. Our results emphasise close associations between HAC and ACC
      lesions in equine centrodistal joints and the importance of ACC lesions in the
      development of OA in low-motion compression-loaded equine joints. 

PMID- 24668596
TI  - Roles of type VI collagen and decorin in human mesenchymal stem cell biophysics
      during chondrogenic differentiation.
AB  - Human mesenchymal stem cells (hMSCs) induced towards chondrogenesis develop a
      pericellular matrix (PCM), rich in type VI collagen (ColVI) and proteoglycans
      such as decorin (DCN). Individual PCM protein functions still need to be
      elucidated to fully understand the mechanobiological role of this matrix. In this
      study we identified ColVI and DCN as important contributors in the mechanical
      function of the PCM and as biochemical modulators during chondrogenesis through
      targeted knockdown using shRNA lentiviral vectors. Gene expression, western
      blotting, immunofluorescence and cell deformation analysis were examined at 7, 14
      and 28 days post chondrogenic induction. ColVI and DCN knockdown each affected
      gene expression of acan, bgn, and sox9 during chondrogenesis. ColVI was found to
      be of central importance in resisting applied strains, while DCN knockdown had
      strain dependent effects on deformation. We demonstrate that by using genetic
      engineering to control the biophysical microenvironment created by
      differentiating cells, it may be possible to guide cellular mechanotransduction. 

PMID- 24668594
TI  - A systematic review of animal models for Staphylococcus aureus osteomyelitis.
AB  - Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for
      orthopaedic patients undergoing surgery, particularly with fracture fixation and
      arthroplasty. Given the difficulty in studying S. aureus infections in human
      subjects, animal models serve an integral role in exploring the pathogenesis of
      osteomyelitis, and aid in determining the efficacy of prophylactic and
      therapeutic treatments. Animal models should mimic the clinical scenarios seen in
      patients as closely as possible to permit the experimental results to be
      translated to the corresponding clinical care. To help understand existing animal
      models of S. aureus, we conducted a systematic search of PubMed and Ovid MEDLINE
      to identify in vivo animal experiments that have investigated the management of
      S. aureus osteomyelitis in the context of fractures and metallic implants. In
      this review, experimental studies are categorised by animal species and are
      further classified by the setting of the infection. Study methods are summarised
      and the relevant advantages and disadvantages of each species and model are
      discussed. While no ideal animal model exists, the understanding of a model's
      strengths and limitations should assist clinicians and researchers to
      appropriately select an animal model to translate the conclusions to the clinical
      setting. 

PMID- 24668597
TI  - "There's gold in them thar hills".

PMID- 24668598
TI  - Understanding the psychology of learning in order to overcome noncompliance.

PMID- 24668599
TI  - A risk-based auditing process for pharmaceutical manufacturers.
AB  - The purpose of this article is to share ideas on developing a risk-based model
      for the scheduling of audits (both internal and external). Audits are a key
      element of a manufacturer's quality system and provide an independent means of
      evaluating the manufacturer's or the supplier/vendor's compliance status.
      Suggestions for risk-based scheduling approaches are discussed in the article.
      LAY ABSTRACT: Pharmaceutical manufacturers are required to establish and
      implement a quality system. The quality system is an organizational structure
      defining responsibilities, procedures, processes, and resources that the
      manufacturer has established to ensure quality throughout the manufacturing
      process. Audits are a component of the manufacturer's quality system and provide
      a systematic and an independent means of evaluating the manufacturer's overall
      quality system and compliance status. Audits are performed at defined intervals
      for a specified duration. The intention of the audit process is to focus on key
      areas within the quality system and may not cover all relevant areas during each
      audit. In this article, the authors provide suggestions for risk-based scheduling
      approaches to aid pharmaceutical manufacturers in identifying the key focus areas
      for an audit.

PMID- 24668600
TI  - Gamma sterilization of pharmaceuticals--a review of the irradiation of
      excipients, active pharmaceutical ingredients, and final drug product
      formulations.
AB  - Sterilization by gamma irradiation has shown a strong applicability for a wide
      range of pharmaceutical products. Due to the requirement for terminal
      sterilization where possible in the pharmaceutical industry, gamma sterilization
      has proven itself to be an effective method as indicated by its acceptance in the
      European Pharmacopeia and the United States Pharmacopeia ( ). Some of the
      advantages of gamma over competitive procedures include high penetration power,
      isothermal character (small temperature rise), and no residues. It also provides
      a better assurance of product sterility than aseptic processing, as well as lower
      validation demands. Gamma irradiation is capable of killing microorganisms by
      breaking their chemical bonds, producing free radicals that attack the nucleic
      acid of the microorganism. Sterility by gamma irradiation is achieved mainly by
      the alteration of nucleic acid and preventing the cellular division. This review
      focuses on the extensive application of gamma sterilization to a wide range of
      pharmaceutical components including active pharmaceutical ingredients,
      excipients, final drug products, and combination drug-medical devices. A summary
      of the published literature for each class of pharmaceutical compound or product
      is presented. The irradiation conditions and various quality control
      characterization methodologies that were used to determine final product quality
      are included, in addition to a summary of the investigational outcomes. Based on
      this extensive literature review and in combination with regulatory guidelines
      and other published best practices, a decision tree for implementation of gamma
      irradiation for pharmaceutical products is established. This flow chart further
      facilitates the implementation of gamma irradiation in the pharmaceutical
      development process. The summary therefore provides a useful reference to the
      application and versatility of gamma irradiation for pharmaceutical
      sterilization. LAY ABSTRACT: Many pharmaceutical products require sterilization
      to ensure their safe and effective use. Sterility is therefore a critical quality
      attribute and is essential for direct injection products. Due to the requirement
      for terminal sterilization, where possible in the pharmaceutical industry
      sterilization by gamma irradiation has been commonly used as an effective method
      to sterilize pharmaceutical products as indicated by its acceptance in the
      European Pharmacopeia. Gamma sterilization is a very attractive terminal
      sterilization method in view of its ability to attain 10(-6) probability of
      microbial survival without excessive heating of the product or exposure to toxic
      chemicals. However, radiation compatibility of a product is one of the first
      aspects to evaluate when considering gamma sterilization. Gamma radiation
      consists of high-energy photons that result in the generation of free radicals
      and the subsequent ionization of chemical bonds, leading to cleavage of DNA in
      microorganisms and their subsequent inactivation. This can result in a loss of
      active pharmaceutical ingredient potency, the creation of radiolysis by-products,
      a reduction of the molecular weight of polymer excipients, and influence drug
      release from the final product. There are several strategies for mitigating
      degradation effects, including optimization of the irradiation dose and
      conditions. This review will serve to highlight the extensive application of
      gamma sterilization to a broad spectrum of pharmaceutical components including
      active pharmaceutical ingredients, excipients, final drug products, and
      combination drug-medical devices.

PMID- 24668602
TI  - Filling of high-concentration monoclonal antibody formulations into pre-filled
      syringes: filling parameter investigation and optimization.
AB  - Syringe filling, especially the filling of high-concentration/viscosity
      monoclonal antibody formulations, is a complex process that has not been widely
      published in literature. This study sought to increase the body of knowledge for
      syringe filling by analyzing and optimizing the filling process from the
      perspective of a fluid's physical properties (e.g., viscosity, concentration,
      surface tension). A bench-top filling unit, comprising a peristaltic pump unit
      and a filling nozzle integrated with a linear actuator, was utilized; glass
      nozzles were employed to visualize liquid flow inside the nozzle with a high
      speed camera. The desired outcome of process optimization was to establish a
      clean filling cycle (e.g., absence of splashes, bubbles, and foaming during
      filling and absence of dripping from the fill nozzle post-fill) and minimize the
      risk of nozzle clogging during nozzle idle time due to formulation drying at or
      near the nozzle tip. The key process variables were determined to be nozzle size,
      airflow around the nozzle tip, pump suck-back (SB)/reversing, fluid viscosity,
      and protein concentration, while pump velocity, acceleration, and fluid/nozzle
      interphase properties were determined to be relatively weak parameters. The SB
      parameter played an especially critical role in nozzle clogging. This study shows
      that an appropriate combination of optimal SB setting, nozzle size, and airflow
      conditions could effectively extend nozzle idle time in a large-scale filling
      facility and environment. LAY ABSTRACT: Syringe filling can be considered a well
      established manufacturing process and has been implemented by numerous contract
      manufacturing organizations and biopharmaceutical companies. However, its
      technical details and associated critical process parameters are rarely
      published. The information on high-concentration/viscosity formulation filling is
      particularly lacking. The purpose of this study is three-fold: (1) to reveal
      design details of a bench-top syringe filling unit; (2) to identify and optimize
      critical process parameters; (3) to apply the learning to practical filling
      operation. The outcomes of this study will benefit scientists and engineers who
      develop pre-filled syringe products by providing a better understanding of HC
      formulation filling principles and challenges.

PMID- 24668601
TI  - Bilayer Tablet Formulation of Metformin HCl and Acarbose: A Novel Approach To
      Control Diabetes.
AB  - The present investigation studied a novel bilayer tablet having an extended
      release system of metformin HCl with Eudragit RS 100 and RL 100 and an immediate
      release system of acarbose with polyvinylpyrrolidone K30 (PVP K30) and
      polyethylene glycol 6000 (PEG 6000) in different ratios using solvent evaporation
      and cogrinding techniques. Solid dispersions (SDs) were characterized by Fourier
      transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC),
      powder x-ray diffractometry (XRD), scanning electron microscopy (SEM), as well as
      by content uniformity, in vitro dissolution studies, and release kinetics. The
      selected SD system was subjected to bilayer tablet preparation by direct
      compression. Compressed tablets were evaluated for drug content, weight
      variation, friability, hardness, and thickness, and they underwent in vitro
      dissolution studies. The progressive disappearance of IR, x-ray, and thermotropic
      drug signals in SDs and physical mixtures were related to increasing amount of
      polymer. SEM studies suggested the homogenous dispersion of drug in polymers. FT
      IR studies confirmed the formation of hydrogen bonding between drug and polymer.
      All tablet formulations showed compliance with pharmacopoeial standards. The
      formulations gave an initial burst effect to provide the loading dose of the drug
      followed by extended release for 12 h (Higuchi model via a non-Fickian diffusion
      controlled release mechanism). Stability studies conducted for the optimized
      formulation did not show any change in physical properties, drug content, or in
      vitro drug release. LAY ABSTRACT: The goal of diabetes therapy today is to
      achieve and maintain as near normal glycemia as possible to prevent the long-term
      microvascular and macrovascular complications of elevated blood glucose levels.
      Oral therapeutic options for the treatment of type 2 diabetes mellitus, until
      recently, have been severely limited. Metformin, a biguanide, targets additional
      mechanisms of hyperglycemia by inhibiting hepatic glucose production and
      enhancing peripheral glucose uptake and thereby reducing insulin resistance;
      acarbose reversibly bind to pancreatic alpha-amylase and membrane-bound
      intestinal alpha-glucoside hydrolases. These enzymes inhibit hydrolysis of
      complex starches to oligosaccharides in the lumen of the small intestine and
      hydrolysis of oligosaccharides, trisaccharides, and disaccharides to glucose and
      other monosaccharides in the brush border of the small intestine. The two agents
      were found to have a remarkable effect on glycemic control. In the present
      investigation a bilayer tablet was prepared in which one layer gives instant
      action against diabetes and another layer maintain concentration of drug in
      plasma for longer periods.

PMID- 24668603
TI  - Fluorescence-based method and a device for rapid detection of microbial
      contamination.
AB  - A method for rapid detection of microbial detection is presented. It uses the
      reduction of resazurin to resorufin as an indication of the presence of viable
      cells. The method is highly sensitive (limit of detection 1 CFU/mL) and rapid
      (detection time 180 s). A portable device that could allow the detection to be
      performed in the field is also described. LAY ABSTRACT: Simple techniques to
      detect microbial contamination are needed. In particular, these need to be user
      friendly and low-cost. In addition, field use capability is desirable. In this
      paper, we describe a device and method that has the above features.

PMID- 24668604
TI  - Use of a real-time microbial air sampler for operational cleanroom monitoring.
AB  - A sampler that detects and counts viable particles in the air of cleanrooms in
      real-time was studied. It was found that when the sampler was used to monitor
      airborne particles dispersed from a number of materials used in cleanrooms,
      including garments, gloves, and skin, the number of viable particles dispersed
      from these materials was greater than anticipated. It was concluded that a
      substantial proportion of these viables were of a non-microbiological origin.
      When the sampler was used to monitor a non-unidirectional airflow cleanroom
      occupied by personnel wearing cleanroom garments, it was found that the airborne
      viable concentrations were unrealistically high and variable in comparison to
      microbe-carrying particles simultaneously measured with efficient microbial air
      samplers. These results confirmed previously reported ones obtained from a
      different real-time sampler. When the real-time sampler was used in a workstation
      within the same cleanroom, the recorded viables gave results that suggest that
      the sampler may provide an effective airborne monitoring method, but more
      investigations are required. LAY ABSTRACT: The airborne concentrations measured
      by a real-time microbial air sampler within an operational, non-unidirectional
      airflow cleanroom were found to be unrealistically high due to a substantial
      numbers of particles of non-microbiological origin. These particles, which
      resulted in false-positive microbial counts, were found to be associated with a
      number of materials used in cleanrooms. When the sampler was used within a
      cleanroom workstation, the counts appeared to be more realistic and suggest that
      this type of real-time airborne microbial counter may provide a useful monitoring
      method in such workstations, but further investigations are required.

PMID- 24668605
TI  - FDA 2011 process validation guidance: lifecycle compliance model.
AB  - This article has been written as a contribution to the industry's efforts in
      migrating from a document-driven to a data-driven compliance mindset. A
      combination of target product profile, control engineering, and general sum
      principle techniques is presented as the basis of a simple but scalable lifecycle
      compliance model in support of modernized process validation. Unit operations and
      significant variables occupy pole position within the model, documentation
      requirements being treated as a derivative or consequence of the modeling
      process. The quality system is repositioned as a subordinate of system quality,
      this being defined as the integral of related "system qualities". The article
      represents a structured interpretation of the U.S. Food and Drug Administration's
      2011 Guidance for Industry on Process Validation and is based on the author's
      educational background and his manufacturing/consulting experience in the
      validation field. LAY ABSTRACT: The U.S. Food and Drug Administration's Guidance
      for Industry on Process Validation (2011) provides a wide-ranging and rigorous
      outline of compliant drug manufacturing requirements relative to its 20(th)
      century predecessor (1987). Its declared focus is patient safety, and it
      identifies three inter-related (and obvious) stages of the compliance lifecycle.
      Firstly, processes must be designed, both from a technical and quality
      perspective. Secondly, processes must be qualified, providing evidence that the
      manufacturing facility is fully "roadworthy" and fit for its intended purpose.
      Thirdly, processes must be verified, meaning that commercial batches must be
      monitored to ensure that processes remain in a state of control throughout their
      lifetime.

PMID- 24668606
TI  - Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro
      and in Kenyan schoolchildren.
AB  - SCOPE: This study explores the relationship between aflatoxin and the insulin
      like growth factor (IGF) axis and its potential effect on child growth. METHODS
      AND RESULTS: One hundred and ninety-nine Kenyan schoolchildren were studied for
      aflatoxin-albumin adduct (AF-alb), IGF1 and IGF-binding protein-3 (IGFBP3) levels
      using ELISA. AF-alb was inversely associated with IGF1 and IGFBP3 (p < 0.05).
      Both IGF1 and IGFBP3 were significantly associated with child height and weight
      (p < 0.01). Children in the highest tertile of AF-alb exposure (>198.5 pg/mg)
      were shorter than children in the lowest tertile (<74.5 pg/mg), after adjusting
      for confounders (p = 0.043). Path analysis suggested that IGF1 levels explained
      ~16% of the impact of aflatoxin exposure on child height (p = 0.052). To further
      investigate this putative mechanistic pathway, HHL-16 liver cells (where HHL-16
      is human hepatocyte line 16 cells) were treated with aflatoxin B1 (0.5, 5 and 20
      MUg/mL for 24-48 h). IGF1 and IGFBP3 gene expression measured by quantitative PCR
      and protein in culture media showed a significant down-regulation of IGF genes
      and reduced IGF protein levels. CONCLUSION: Aflatoxin treatment resulted in a
      significant decrease in IGF gene and protein expression in vitro. IGF protein
      levels were also lower in children with the highest levels of AFB-alb adducts.
      The data suggest that aflatoxin-induced changes in IGF protein levels could
      contribute to growth impairment where aflatoxin exposure is high.

PMID- 24668608
TI  - Combined glucose ingestion and mouth rinsing improves sprint cycling performance.
AB  - This study investigated whether combined ingestion and mouth rinsing with a
      carbohydrate solution could improve maximal sprint cycling performance. Twelve
      competitive male cyclists ingested 100 ml of one of the following solutions 20
      min before exercise in a randomized double-blinded counterbalanced order (a) 10%
      glucose solution, (b) 0.05% aspartame solution, (c) 9.0% maltodextrin solution,
      or (d) water as a control. Fifteen min after ingestion, repeated mouth rinsing
      was carried out with 11 * 15 ml bolus doses of the same solution at 30-s
      intervals. Each participant then performed a 45-s maximal sprint effort on a
      cycle ergometer. Peak power output was significantly higher in response to the
      glucose trial (1188 +/- 166 W) compared with the water (1036 +/- 177 W),
      aspartame (1088 +/- 128 W) and maltodextrin (1024 +/- 202 W) trials by 14.7 +/-
      10.6, 9.2 +/- 4.6 and 16.0 +/- 6.0% respectively (p < .05). Mean power output
      during the sprint was significantly higher in the glucose trial compared with
      maltodextrin (p < .05) and also tended to be higher than the water trial (p =
      .075). Glucose and maltodextrin resulted in a similar increase in blood glucose,
      and the responses of blood lactate and pH to sprinting did not differ
      significantly between treatments (p > .05). These findings suggest that combining
      the ingestion of glucose with glucose mouth rinsing improves maximal sprint
      performance. This ergogenic effect is unlikely to be related to changes in blood
      glucose, sweetness, or energy sensing mechanisms in the gastrointestinal tract.

PMID- 24668607
TI  - "East asian paradox": challenge for the current antiplatelet strategy of "one
      guideline-fits-all races" in acute coronary syndrome.
AB  - Clinical experiences have suggested that East Asians show the higher risk of
      warfarin-related intracranial hemorrhage compared with Westerners. Therefore,
      different target of the International Normalized Ratio (INR) in East Asians (1.6
      2.6) has been proposed and adapted in clinical practice. In terms with
      antiplatelet therapy, recent evidence has supported the concept of "therapeutic
      level of platelet reactivity" to balance clinical efficacy and safety in patients
      undergoing percutaneous coronary intervention (PCI) or those with acute coronary
      syndrome (ACS). In line with the warfarin experiences, multiple clinical and
      pharmacodynamic data from East Asians have shown their different therapeutic
      level of platelet reactivity following PCI or ACS ("East Asian Paradox").
      Furthermore, like most cardiovascular drugs, P2Y12 receptor blockers have marked
      interethnic differences in the pharmacokinetics and pharmacodynamics. The
      currently performed clinical trials evaluating the clinical efficacy and safety
      of potent P2Y12 inhibitors mostly don't include enough number of East Asians to
      draw reliable conclusions. Therefore, dedicated research and guideline(s) for
      East Asians are required before we can apply Western recommendations for potent
      P2Y12 inhibitors in East Asian population. It is a time to consider the paradigm
      shift from "one-guideline-fits-all races" to "race-tailored antiplatelet therapy"
      in treating ACS patients. 

PMID- 24668610
TI  - Relationship between survival and increased radiation dose to subventricular zone
      in glioblastoma is controversial.
AB  - To test the hypothesis on prolonged survival in glioblastoma cases with increased
      subventricular zone (SVZ) radiation dose. Sixty glioblastoma cases were
      previously treated with adjuvant radiotherapy and Temozolamide. Ipsilateral,
      contralateral and bilateral SVZs were contoured and their doses were
      retrospectively evaluated. Median follow-up, progression free survival (PFS) and
      overall survival (OS) were 24.5, 8.5 and 19.3 months respectively. Log-rank tests
      showed a statistically significant correlation between contralateral SVZ (cSVZ)
      dose > 59.2 Gy (75th percentile) and poor median PFS (10.37 [95% CI 8.37-13.53]
      vs 7.1 [95% CI 3.5-8.97] months, p = 0.009). cSVZ dose > 59.2 Gy was associated
      with poor OS in the subgroup with subtotal resection/biopsy (HR: 4.83 [95% CI
      1.71-13.97], p = 0.004). High ipsilateral SVZ dose of > 62.25 Gy (75th
      percentile) was associated with poor PFS in both subgroups of high performance
      status (HR: 2.58 [95% CI 1.03-6.05], p = 0.044) and SVZ without tumoral contact
      (HR: 10.57 [95% CI 2.04-49], p = 0.008). The effect of high cSVZ dose on PFS lost
      its statistical significance in multivariate Cox regression analysis. We report
      contradictory results compared to previous publications. Changing the clinical
      practice based on retrospective studies which even do not indicate consistent
      results among each other will be dangerous. We need carefully designed
      prospective randomized studies to evaluate any impact of radiation to SVZ in
      glioblastoma.

PMID- 24668609
TI  - Preclinical evaluation of the combination of mTOR and proteasome inhibitors with
      radiotherapy in malignant peripheral nerve sheath tumors.
AB  - About one half of malignant peripheral nerve sheath tumors (MPNST) have
      Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for
      negative regulation of RAS signaling. Survival for MPNST patients is poor and we
      sought to identify an effective combination therapy. Starting with the mTOR
      inhibitors rapamycin and everolimus, we screened for synergy in 542 FDA approved
      compounds using MPNST cells with a native NF1 loss in both alleles. We further
      analyzed the cell cycle and signal transduction. In vivo growth effects of the
      drug combination with local radiation therapy (RT) were assessed in MPNST
      xenografts. The synergistic combination of mTOR inhibitors with bortezomib
      yielded a reduction in MPNST cell proliferation. The combination of mTOR
      inhibitors and bortezomib also enhanced the anti-proliferative effect of
      radiation in vitro. In vivo, the combination of mTOR inhibitor (everolimus) and
      bortezomib with RT decreased tumor growth and proliferation, and augmented
      apoptosis. The combination of approved mTOR and proteasome inhibitors with
      radiation showed a significant reduction of tumor growth in an animal model and
      should be investigated and optimized further for MPNST therapy. 

PMID- 24668611
TI  - Calibration plots for risk prediction models in the presence of competing risks.
AB  - A predicted risk of 17% can be called reliable if it can be expected that the
      event will occur to about 17 of 100 patients who all received a predicted risk of
      17%. Statistical models can predict the absolute risk of an event such as
      cardiovascular death in the presence of competing risks such as death due to
      other causes. For personalized medicine and patient counseling, it is necessary
      to check that the model is calibrated in the sense that it provides reliable
      predictions for all subjects. There are three often encountered practical
      problems when the aim is to display or test if a risk prediction model is well
      calibrated. The first is lack of independent validation data, the second is right
      censoring, and the third is that when the risk scale is continuous, the
      estimation problem is as difficult as density estimation. To deal with these
      problems, we propose to estimate calibration curves for competing risks models
      based on jackknife pseudo-values that are combined with a nearest neighborhood
      smoother and a cross-validation approach to deal with all three problems.

PMID- 24668612
TI  - Elevated IL-8, TNF-alpha, and MCP-1 in men with metastatic prostate cancer
      starting androgen-deprivation therapy (ADT) are associated with shorter time to
      castration-resistance and overall survival.
AB  - BACKGROUND: Chemokines and cytokines have been implicated in progression to
      castration-resistant prostate cancer (CRPC). METHODS: Retrospective data were
      accessed from 122 men with serum samples drawn at a median of 0.5 months after
      starting ADT for metastatic prostate cancer. MCP-1, IL-1-beta, IL-2, IL-8, IL-6,
      and TNF-alpha levels were measured by multiplex electrochemiluminescence assays.
      A multivariable Cox model assessed the association of time to CRPC and overall
      survival by the protein levels and adjusted for clinical variables (age and
      prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, and
      extent of metastases). Associations were reported as hazard ratio (HR) with 95%
      confidence interval (CI). RESULTS: Median follow-up and overall survival were 44
      and 42.2 months, respectively. ECOG performance status (>=1 vs. 0) was negatively
      associated with overall survival [HR = 2.8 (1.1-7.0), P = 0.03], and PSA nadir <
      0.2 was predictive of longer time to development of CRPC [HR = 0.3 (0.2-0.5), P <
      0.0001]. The HR for time to CRPC by protein above the median was 1.4 (95% CI:
      0.9, 2.2, P = 0.13) for IL-8; 1.3 (95% CI: 0.8, 2, P = 0.18) for TNF-alpha; 1.0
      (95% CI: 0.7, 1.6, P = 0.95) for MCP-1. The HR for median overall survival for
      protein levels above the median was: 1.9 (95% CI: 1.0, 3.5, P = 0.04) for IL-8;
      2.0 (95% CI: 1.1, 3.5, P = 0.02) for TNF-alpha; 1.7 (95% CI: 1.7, 3.0, P = 0.08)
      for MCP-1. There was no association with IL-1-beta, IL-2, or IL-6. CONCLUSION:
      Higher levels of inflammation-associated cytokines correlate with poorer prostate
      cancer outcomes and may guide strategies to improve prostate cancer therapy.

PMID- 24668613
TI  - Use and impact of adjuvant chemotherapy in patients with resected non-small cell
      lung cancer.
AB  - BACKGROUND: Despite clinical trials demonstrating improved survival with adjuvant
      chemotherapy (AC) for patients with American Joint Committee on Cancer stages I
      to III non-small cell lung cancer (NSCLC), it is unclear whether this survival
      benefit extends to broader populations. The current study evaluated patterns of
      AC use and examined the impact of AC on survival. METHODS: A retrospective
      analysis was conducted of patients in the Veterans Affairs Central Cancer
      Registry diagnosed with stages IB to IIIA NSCLC between 2001 and 2008.
      Descriptive statistics were used to examine patterns of AC use over an 8-year
      time period. Cox proportional hazards regression analyses were used to estimate
      hazards ratios (HR) and 95% confidence intervals (95% CIs) to compare mortality
      risk among patients treated with and without AC. RESULTS: Among 14,306 patients
      with stages IB to IIIA NSCLC, 4929 underwent surgery and 22% of these received
      AC. The percentages of patients diagnosed in 2001 through 2003, 2004 through
      2005, and 2006 through 2008 receiving AC were 7.0%, 29.8%, and 29.5%,
      respectively. There was no survival benefit with AC noted for patients diagnosed
      between 2001 and 2003, but AC was associated with improved survival for the
      period between 2004 and 2005 (HR, 0.78; 95% CI, 0.67-0.91) and 2006 through 2008
      (HR, 0.79; 95% CI, 0.69-0.91). Of those patients receiving AC, 89% received
      platinum-doublet chemotherapy. Carboplatin remained the most common agent,
      although cisplatin use reached 43% in the period between 2006 and 2008. The HR
      for cisplatin relative to carboplatin was 0.96 (95% CI, 0.80-1.15). CONCLUSIONS:
      There was a significant increase in the use of AC between 2001 and 2008 and AC
      was associated with an improvement in overall survival.

PMID- 24668614
TI  - In-body tissue-engineered collagenous connective tissue membranes (BIOSHEETs) for
      potential corneal stromal substitution.
AB  - There is a severe shortage of donor cornea for transplantation in many countries.
      Collagenous connective tissue membranes, named BIOSHEETs, grown in vivo were
      successfully implanted in rabbit corneal stroma for in vivo evaluation of their
      suitability as a corneal stromal substitute to solve this global donor shortage.
      BIOSHEETs were prepared by embedding silicone moulds into dorsal subcutaneous
      pouches in rabbits for 1 month and stored in glycerol. After re-swelling in
      saline and trephining, disk-shaped BIOSHEETs (4 mm diameter) were allogeneically
      implanted into stromal pockets prepared in the right cornea of seven rabbits.
      Clinical tests for corneal thickness and transparency, and tissue analyses were
      performed. Because the BIOSHEETs (thickness, 131 +/- 14 um) obtained were opaque
      immediately after implantation, the transparency of the cornea decreased. The
      total thickness of the BIOSHEET-implanted cornea increased from 364 +/- 21.0 um
      to 726 +/- 131 um. After 4 weeks' implantation, the thickness of the cornea
      stabilized (493 +/- 80 um at 4 weeks and 447 +/- 46 um at 8 weeks). The
      transparency of the cornea increased progressively with time of implantation. The
      random orientation of collagen fibrils in the original BIOSHEETs tended to be
      homogeneous, similar to that of the native stroma. No inflammatory cells
      accumulated and fibroblast-like cells infiltrated the implant. The BIOSHEETs
      showed high biocompatibility with stromal tissues; however, further studies are
      needed to test its functional aspects. Although this research is only intended as
      a proof of concept, BIOSHEETs may be considered a feasible corneal stromal
      replacement, especially for treating visual impairment caused by stromal haze.
      Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668616
TI  - Lung function by impulse oscillometry at age 5-7 years after bronchiolitis at age
      0-6 months.
AB  - BACKGROUND: Viral bronchiolitis in infancy has been associated with increased
      bronchial reactivity and reduced lung function in later childhood and even in
      adulthood. However, lung function at preschool age is less studied, mainly due to
      technical difficulties. The purpose of the study was to evaluate lung function
      and bronchial reactivity at preschool age in children who were hospitalized for
      bronchiolitis in early infancy. SUBJECTS AND METHODS: Airway resistance and
      reactance, and bronchial reactivity to exercise were studied with impulse
      oscillometry (IOS) at the mean age of 6.3 years in 103 children hospitalized for
      bronchiolitis at less than 6 months of age. RESULTS: In baseline lung-function
      measurement, resistance (n = 8; 7.8%) or reactance (19; 18.4%) at 5 Hz were
      pathological in 20% of children compared to Finnish population-based height
      adjusted reference values. Increased bronchial reactivity by exercise challenge
      (5; 4.9%) or bronchodilatation (11; 10.7%) tests was present in 16%. Irreversible
      changes were revealed in only one case. CONCLUSIONS: Though reduced lung function
      and increased airway reactivity were rather common, evidence for persistent lung
      function reduction was rare, less than 1%, at preschool age in children
      hospitalized for bronchiolitis caused mainly by respiratory syncytial virus at
      age less than 6 months.

PMID- 24668615
TI  - Dissociable effects of basolateral amygdala lesions on decision making biases in
      rats when loss or gain is emphasized.
AB  - Individuals switch from risk seeking to risk aversion when mathematically
      identical options are described in terms of loss versus gains, as exemplified in
      the reflection and framing effects. Determining the neurobiology underlying such
      cognitive biases could inform our understanding of decision making in health and
      disease. Although reports vary, data using human subjects have implicated the
      amygdala in such biases. Animal models enable more detailed investigation of
      neurobiological mechanisms. We therefore tested whether basolateral amygdala
      (BLA) lesions would affect risk preference for gains or losses in rats. Choices
      in both paradigms were always between options of equal expected value-a
      guaranteed outcome, or the 50:50 chance of double or nothing. In the loss-chasing
      task, most rats exhibited strong risk seeking preferences, gambling at the risk
      of incurring double the penalty, regardless of the size of the guaranteed loss.
      In the betting task, the majority of animals were equivocal in their choice,
      irrespective of bet size; however, a wager-sensitive subgroup progressively
      shifted away from the uncertain option as the bet size increased, which is
      reminiscent of risk aversion. BLA lesions increased preference for the smaller
      guaranteed loss in the loss-chasing task, without affecting choice on the betting
      task, which is indicative of reduced risk seeking for losses, but intact risk
      aversion for gains. These data support the hypothesis that the amygdala plays a
      more prominent role in choice biases related to losses. Given the importance of
      the amygdala in representing negative affect, the aversive emotional reaction to
      loss, rather than aberrant estimations of probability or loss magnitude, may
      underlie risk seeking for losses. 

PMID- 24668617
TI  - Redox control of enzymatic functions: The electronics of life's circuitry.
AB  - The field of redox biology has changed tremendously over the past 20 years.
      Formerly regarded as bi-products of the aerobic metabolism exclusively involved
      in tissue damage, reactive oxygen species (ROS) are now recognized as active
      participants of cell signaling events in health and in disease. In this sense,
      ROS and the more recently defined reactive nitrogen species (RNS) are, just like
      hormones and second messengers, acting as fundamental orchestrators of cell
      signaling pathways. The chemical modification of enzymes by ROS and RNS (that
      result in functional enzymatic alterations) accounts for a considerable fraction
      of the transient and persistent perturbations imposed by variations in oxidant
      levels. Upregulation of ROS and RNS in response to stress is a common cellular
      response that foments adaptation to a variety of physiologic alterations
      (hypoxia, hyperoxia, starvation, and cytokine production). Frequently, these are
      beneficial and increase the organisms' resistance against subsequent acute stress
      (preconditioning). Differently, the sustained ROS/RNS-dependent rerouting of
      signaling produces irreversible alterations in cellular functioning, often
      leading to pathogenic events. Thus, the duration and reversibility of protein
      oxidations define whether complex organisms remain "electronically" healthy.
      Among the 20 essential amino acids, four are particularly susceptible to
      oxidation: cysteine, methionine, tyrosine, and tryptophan. Here, we will
      critically review the mechanisms, implications, and repair systems involved in
      the redox modifications of these residues in proteins while analyzing well
      characterized prototypic examples. Occasionally, we will discuss potential
      consequences of amino acid oxidation and speculate on the biologic necessity for
      such events in the context of adaptative redox signaling. (c) 2014 IUBMB Life,
      66(3):167-181, 2014.

PMID- 24668618
TI  - Microporous metal-organic frameworks for gas separation.
AB  - Microporous metal-organic frameworks (MOFs) are comparatively new porous
      materials. Because the pores within such MOFs can be readily tuned through the
      interplay of both metal-containing clusters and organic linkers to induce their
      size-selective sieving effects, while the pore surfaces can be straightforwardly
      functionalized to enforce their different interactions with gas molecules, MOF
      materials are very promising for gas separation. Furthermore, the high porosities
      of such materials can enable microporous MOFs with optimized gas separation
      selectivity and capacity to be targeted. This Focus Review highlights recent
      significant advances in microporous MOFs for gas separation. 

PMID- 24668619
TI  - Isolated terminal limb reduction defects: extending the clinical spectrum of
      Adams-Oliver syndrome and ARHGAP31 mutations.
AB  - Adams-Oliver syndrome (AOS; OMIM 100300) typically comprises a combination of
      congenital scalp defects and terminal transverse limb defects. Recently,
      mutations in ARHGAP31 and RBPJ have been found causing autosomal dominant forms
      of AOS. We describe a four-generation pedigree with isolated terminal limb
      defects and a truncating mutation in ARHGAP31. This finding underscores the
      relevance of sequencing ARHGAP31 in similar cases of isolated limb defects,
      irrespective of the presence of a complete AOS phenotype. We also highlight the
      variability of clinical features among mutation carriers, ranging from severe
      reduction defects to mild as well as clinically unaffected cases suggesting
      reduced penetrance.

PMID- 24668620
TI  - Sports Dietitians Australia position statement: sports nutrition for the
      adolescent athlete.
AB  - It is the position of Sports Dietitians Australia (SDA) that adolescent athletes
      have unique nutritional requirements as a consequence of undertaking daily
      training and competition in addition to the demands of growth and development. As
      such, SDA established an expert multidisciplinary panel to undertake an
      independent review of the relevant scientific evidence and consulted with its
      professional members to develop sports nutrition recommendations for active and
      competitive adolescent athletes. The position of SDA is that dietary education
      and recommendations for these adolescent athletes should reinforce eating for
      long term health. More specifically, the adolescent athlete should be encouraged
      to moderate eating patterns to reflect daily exercise demands and provide a
      regular spread of high quality carbohydrate and protein sources over the day,
      especially in the period immediately after training. SDA recommends that
      consideration also be given to the dietary calcium, Vitamin D and iron intake of
      adolescent athletes due to the elevated risk of deficiency of these nutrients. To
      maintain optimal hydration, adolescent athletes should have access to fluids that
      are clean, cool and supplied in sufficient quantities before, during and after
      participation in sport. Finally, it is the position of SDA that nutrient needs
      should be met by core foods rather than supplements, as the recommendation of
      dietary supplements to developing athletes over-emphasizes their ability to
      manipulate performance in comparison with other training and dietary strategies. 

PMID- 24668621
TI  - When and how to treat patients who refuse treatment.

PMID- 24668622
TI  - Magnetic coupling and optical properties of the S6
      dodecakis(trifluoromethyl)fullerene radical anions in the layered salt
      (PPN(+))[C60(CF3)12(.-)].
AB  - Poly(trifluoromethyl)fullerene S6-C60(CF3)12 was reduced by sodium fluorenone
      ketyl in the presence of (PPN)Cl (PPN = bis(triphenylphosphine)iminium) to afford
      the salt (PPN)[C60(CF3)12] (1), which contains C60(CF3)12(.-) radical anions. In
      the crystal structure of 1, C60(CF3)12(.-) layers alternate with the PPN(+)
      cations. There are short F???F contacts between C60(CF3)12(.-) radical anions
      within the layers but no C???C contacts. DFT calculations revealed that the
      negative charge on C60(CF3)12(.-) is distributed mainly between sp(2) carbon and
      fluorine atoms, whereas spin density is localized mainly on the fullerene-cage
      sp(2) carbon atoms. IR and UV/Vis/NIR spectra in the solid state and solution
      showed characteristic changes relative to those of neutral S6-C60(CF3)12 due to
      the formation of radical anions. The solid-state electronic spectrum of 1
      exhibits a single broad band at 738 nm attributed to C60(CF3)12(.-). Crystals of
      1 show a narrow EPR signal with g = 2.0025 (DeltaH = 0.45 mT) at 300 K. The
      temperature dependence of the integral intensity follows the Curie-Weiss law with
      a negative Weiss temperature of -11.8 K (30-300 K) indicating antiferromagnetic
      interaction of spins. This dependence was approximated by the Heisenberg model
      for one-dimensional chains of antiferromagnetically interacting spins with
      exchange interaction J/kB = -9.1 K. It was assumed that magnetic interaction
      between the C60(CF3)12(.-) spins in the layers is mediated by short F???F
      contacts.

PMID- 24668623
TI  - TPH2 gene polymorphisms in the regulatory region are associated with paranoid
      schizophrenia in Northern Han Chinese.
AB  - In the last years, serotonin (5-HT) has been related with the pathophysiology of
      several psychiatric disorders, including schizophrenia. Thus, genes related to
      the serotonergic (5-HTergic) system are good candidate genes for schizophrenia.
      The rate-limiting enzyme of 5-HT synthesis is tryptophan hydroxylase 2 (TPH2).
      Single nucleotide polymorphisms (SNPs) in the regulatory regions of TPH2 gene may
      affect gene expression and biosynthesis of 5-HT triggering to various
      neuropsychiatric disorders related to 5-HT dysfunction. The present study
      explored the association of SNPs within the TPH2 gene with paranoid schizophrenia
      in Han Chinese. A total of 164 patients with schizophrenia and 244 healthy
      controls were genotyped for six TPH2 SNPs (rs4570625, rs11178997, rs11178998,
      rs41317118, rs17110747, and rs41317114). Significant group differences were
      observed in the allele and genotype frequencies of rs4570625 and in the
      frequencies of GTA and TTA haplotypes corresponding to rs4570625-rs11178997
      rs11178998. Our findings suggest that common genetic variations of TPH2 are
      likely to contribute to genetic susceptibility to paranoid schizophrenia in Han
      Chinese. Further studies in larger samples are needed to replicate this
      association. 

PMID- 24668624
TI  - Development and characterization of SSR markers from Pinus massoniana and their
      transferability to P. elliottii, P. caribaea and P. yunnanensis.
AB  - Pinus massoniana (Masson's pine) is a widespread tree species in central and
      southern China and northern Vietnam; it is valued for rosin and paper production.
      Despite the significant economic value of Masson's pine, little work has been
      done on its molecular genetics. We developed 318 SSR primers from genome
      sequences of P. massoniana, and we identified 10 polymorphic markers. The number
      of alleles in the population of P. massoniana that we examined ranged from two to
      four, and the Shannon diversity index ranged from 0.150 to 1.133. Cross-species
      transferability of the 318 SSRs was also analyzed in the slash pine (Pinus
      elliottii), the Caribbean pine (Pinus caribaea) and the Yunnan pine (Pinus
      yunnanensis); 15, 10, and 10 primer pairs generated polymorphic amplification,
      respectively. These sets of polymorphic SSR markers will be useful for population
      genetics studies of P. massoniana, for genetic identification of interspecific
      hybridization, and for phylogeographic studies of Pinus spp. 

PMID- 24668625
TI  - Isolation and characterization of polymorphic microsatellite loci from aerial yam
      (Dioscorea bulbifera L.).
AB  - Dioscorea bulbifera L. is widely distributed in pantropical regions along the
      equator. The taxonomic treatment of this species is ambiguous due to its extreme
      polymorphic morphological characters. In order to provide tools to facilitate the
      study of genetic diversity, population structure, patterns of gene flow, and the
      mating system of this species, and to assess intraspecific variability and
      relationships in D. bulbifera, 14 novel polymorphic microsatellite loci were
      developed using the dual-suppression PCR technique. The number of alleles per
      locus ranged from 4 to 17, with an average of 9.93. The mean observed
      heterozygosities were 0.7327 and 0.7223, and the mean Shannon-Wiener indices were
      1.6431 and 1.811 in the Nanjing and Nanchong populations, respectively. All novel
      microsatellite loci showed high levels of polymorphism, indicating that these
      markers offer great potential significance and profound influence for future
      studies of this species. 

PMID- 24668626
TI  - Investigation of mutations in the SRY, SOX9, and DAX1 genes in sex reversal
      patients from the Sichuan region of China.
AB  - We investigated the molecular genetic mechanism of sex reversal by exploring the
      relationship between mutations in the sex-determining genes SRY, SOX9, and DAX1
      with genetic sex reversal disease. Mutations in the three key genes were detected
      by polymerase chain reaction (PCR) and sequencing after karyotype analysis. The
      mutations detected were then aligned with a random sample of 100 normal sequences
      and the NCBI sequence database in order to confirm any new mutations.
      Furthermore, the copy number of SOX9 was measured by fluorescence quantitative
      PCR. Seven of the 10 male sex reversal patients (46, XX) contained an excess copy
      of the SRY gene, while one of the eight female sex reversal patients (46, XY) was
      lacking the SRY gene. Additionally, a new mutation (T-A, Asp24Lys) was detected
      in one female sex reversal patient (46, XY). No other mutation was detected in
      the analysis of SOX9 and DAX1, with the exception of an insertion mutation
      (c.35377791insG) found in the testicular-specific enhancer (TESCO) sequences in
      an SRY-positive female sex reversal patient (46, XY). Eight of the 18 sex
      reversal cases (44.4%) showed obvious connections with SRY gene translocations,
      mutations, or deletions, which was significantly higher than that reported
      previously (33.3%), indicating a need to further expand the range of sample
      collection. Overall, these results indicated that the main mechanism of sex
      reversal are not associated with mutations in the coding regions of SOX9 and DAX1
      or copy number variations of SOX9, which is consistent with results of previous
      studies. 

PMID- 24668627
TI  - Molecular cloning and immune response analysis of putative variable lipoproteins
      from Mycoplasma mycoides subsp capri.
AB  - Mycoplasma mycoides subsp capri is the cause of goat "MAKePS" (Mastitis,
      Arthritis, Keratoconjunctivitis, Pneumonia, Septicemia) syndrome. We identified
      three genes (GL_ 000459; 000461; 000462) as variable lipoprotein genes in the M.
      mycoides subsp capri str. PG3 genome by genomic information and comparative
      genomic analyses. To study the role of variable lipoproteins in M. mycoides subsp
      capri pathogenesis and evaluate the immunogenic and protective potentials of
      those proteins, we constructed the expression systems and expressed the mature
      peptide portion of the three proteins in E. coli. We also determined the titers
      and opsonophagocytosis activity of total IgG antibodies and the levels of Th1 and
      Th2 cytokines in sera, and we ran a lymphocyte proliferation assay in mice
      immunized with recombinant proteins His-tag-GL000459, His-tag-GL000461, and His
      tag-GL000462. These three lipoproteins induced humoral and cellular immune
      responses in the immunized mice. Additionally, the whole blood opsonophagocitic
      in vitro assay demonstrated that the antibodies produced by the immunized groups
      can neutralize strain PG3; consequently, these three variable lipoproteins could
      be the major surface antigens in M. mycoides subsp capri str. PG3. 

PMID- 24668628
TI  - Effects of porcine circovirus type 2 and pseudorabies vaccine co-inoculation on
      regulatory cytokine mRNA expression in pig peripheral blood mononuclear cells.
AB  - We investigated the immune response effects of porcine circovirus type 2 (PCV2)
      on cells inoculated with pseudorabies attenuated vaccine (PRV). Real-time PCR was
      used to detect the mRNA expression levels of the regulatory cytokines IL-4, IL
      10, IL-12p40, and IFN-gamma in pig peripheral blood mononuclear cells, after in
      vitro single vaccination and co-inoculation with PCV2 and the PRV. We found that
      PRV causes upregulation of IL-4, IL-12p40, and IFN-gamma mRNA expression, while
      PCV2 causes mRNA upregulation of IL-4, IL-10, and IL-12p40. Moreover, PCV2
      inhibited PRV-induced upregulation of IL-4, IL-12p40, and IFN-gamma mRNA
      expression; IFN-gamma mRNA expression was significantly inhibited. We conclude
      that PCV2 can reduce the cellular immune response to PRV. 

PMID- 24668629
TI  - Sequence divergence of microsatellites for phylogeographic assessment of Moroccan
      Medicago species.
AB  - Six Medicago species were investigated to characterize and valorize plant genetic
      resources of pastoral interest in Morocco. Samples were obtained from the core
      collection of the South Australian Research and Development Institute (SARDI).
      The transferability of single sequence repeat markers of Medicago truncatula was
      successful with 97.6% efficiency across the five species. A total of 283 alleles
      and 243 genotypes were generated using seven SSR markers, confirming the high
      level of polymorphism that is characteristic of the Medicago genus, despite a
      heterozygosity deficit (HO = 0.378; HE = 0.705). In addition, a high level of
      gene flow was revealed among the species analyzed with significant intra-specific
      variation. The unweighted pair group method with arithmetic mean dendrogram
      generated by the dissimilarity matrix revealed that M. polymorpha and M.
      orbicularis are closely related, and that M. truncatula is likely the ancestral
      species. The Pearson correlation index revealed no significant correlations
      between the geographic distribution of the Moroccan species and genetic
      similarities, indicating local adaptation of these species to different
      ecological environments independent of their topographical proximities. The
      substantial genetic variation observed was likely due to the predominance of
      selfing species, the relative proximity of prospected sites, human impacts, and
      the nature of the SARDI core collections, which are selected for their high
      genetic diversity. The results of this first report on Moroccan Medicago species
      will be of great interest for establishing strategies aiming at reasonable
      management and selection programs for local and Mediterranean germplasm in the
      face of increasing environmental change. 

PMID- 24668630
TI  - FSHR genotype affects estrogen levels but not pregnancy rates in Luxi cattle
      subjected to embryo transfer.
AB  - Follicle-stimulating hormone receptor (FSHR), which mediates the functioning of
      FSH, plays a central role in reproduction. We investigated bovine FSHR gene
      polymorphisms and analyzed their relationships with pregnancy rates after embryo
      transfer and with hormone concentrations on the day of embryo transfer. One
      reported SNP of FSHR, G-278A, located in the 5'-upstream region, was analyzed and
      three genotypes (GG, GA and AA) were detected in 132 Luxi cattle recipients.
      Statistical analysis revealed that recipients with the GG genotype had
      significantly higher estrogen levels on the day of embryo transfer than did GA
      and AA genotypes. There were no significant differences in pregnancy rates among
      genotypes, after embryo transfer. We conclude that variation at these loci of the
      FSHR gene has no significant effect on pregnancy rates in Luxi cattle. 

PMID- 24668631
TI  - Cell proliferation and apoptosis in the fetal and neonatal ovary of guinea pigs.
AB  - The guinea pig is an excellent animal model for studying reproductive biology of
      adult humans and most domestic animals. Yet, whether this animal might serve as a
      good model for embryonic stage investigations and determinations of signals
      affecting or directing ovary development remains unknown. These questions were
      addressed by examining morphological evolution and the expression of biomarkers
      of cell proliferation and apoptosis in the ovaries of fetal and neonatal guinea
      pigs in the present study. Embryonic and neonatal guinea pigs at 30, 40, 50, 60,
      and 68 days postcoitum (dpc) and at 1 day postpartum (dpp) were evaluated, and
      the dynamic changes in follicles between 30 dpc and 1 dpp were observed. Results
      also showed that a critical period of follicular development in guinea pig
      embryos occurred at 40 to 50 dpc. Moreover, the proliferating-cell nuclear
      antigen, a cell proliferation marker, immunohistochemically stained healthy
      follicles, while caspase-3, an apoptosis marker, was mainly observed in atretic
      follicles. Together, these results demonstrate that cell proliferation and
      apoptosis contribute to follicular formation, development, and atresia in fetal
      and neonatal guinea pig ovaries. Furthermore, this study confirmed that the
      guinea pig is also an excellent animal model for studying reproductive biology in
      human and domestic animal embryos. 

PMID- 24668632
TI  - Phosphate-induced-1 gene from Eucalyptus (EgPHI-1) enhances osmotic stress
      tolerance in transgenic tobacco.
AB  - Environmental stresses such as drought, freezing, and high salinity induce
      osmotic stress in plant cells. The plant response to osmotic stress involves a
      number of physiological and developmental changes, which are made possible, in
      part, by the modulation of the expression of specific genes. Phosphate-induced-1
      gene (PHI-1) was first isolated from phosphate-treated phosphate-starved tobacco
      cell cultures as a stress-inducible gene, which is presumably related to
      intracellular pH maintenance; however, the role of the PHI-1 gene product has not
      yet been clarified. A gene encoding a predicted protein with high similarity to
      tobacco PHI-1, named EgPHI-1, was previously identified in Eucalyptus by
      comparative transcriptome analysis of xylem cells from species of contrasting
      phenotypes for wood quality and growth traits. Here, we show that the
      overexpression of EgPHI-1 in transgenic tobacco enhances tolerance to osmotic
      stress. In comparison with wild-type plants, EgPHI-1 transgenic plants showed a
      significant increase in root length and biomass dry weight under NaCl-,
      polyethylene glycol, and mannitol-induced osmotic stresses. The enhanced stress
      tolerance of transgenic plants was correlated with increased endogenous protein
      levels of the molecular chaperone binding protein BiP, which in turn was
      correlated with the EgPHI-1 expression level in the different transgenic lines.
      These results provide evidence about the involvement of EgPHI-1 in osmotic stress
      tolerance via modulation of BiP expression, and pave the way for its future use
      as a candidate gene for engineering tolerance to environmental stresses in crop
      plants. 

PMID- 24668633
TI  - Preparation and biological activity of a paclitaxel-single-walled carbon nanotube
      complex.
AB  - Single-walled carbon nanotubes (SWCNTs) have unique transmembrane abilities. The
      huge superficial area and abundance of pi electrons confer SWCNTs perfect
      absorptive capability toward proteins, nucleates, and many drugs. These
      characteristics make SWCNTs a new and efficient drug carrier. The purpose of this
      study was to disperse SWCNTs in water and have paclitaxel absorbed onto them in
      order to construct an asparagine-glycine-arginine (NGR)-SWCNT-Paclitaxel complex
      as a targeting nanoparticle system. The NGR-SWCNT-Paclitaxel complex was
      systematically studied, and analytical methods, including spectrophotometry for
      SWCNTs and high-performance liquid chromatography for paclitaxel, were employed.
      The preparation and the prescription of the NGR-SWCNT-Paclitaxel complex
      lyophilized powder were investigated. MCF-7 cancer cells, Sprague-Dawley rats,
      and S180 tumor-bearing mice were used as experimental subjects to evaluate the in
      vitro and in vivo activity of NGR-SWCNT-Paclitaxel complex dispersion. The
      complex dispersion showed obvious inhibition activity against MCF-7 cancer cells.
      Within 1 h, the NGR-SWCNT-Paclitaxel complex could be transferred to cells, and
      sustained the release of drugs. In addition, the tumor and liver targeting and
      improved therapeutic effects of the NGR-SWCNT-Paclitaxel complex were confirmed. 

PMID- 24668634
TI  - Development and characterization of microsatellite markers for Brazilian four
      eyed frogs (genus Pleurodema) endemic to the Caatinga biome.
AB  - We used pyrosequencing to develop microsatellite markers for the Brazilian four
      eyed frog Pleurodema diplolister and tested the microsatellite markers for cross
      amplification in its sister Pleurodema alium, which are both endemic species of
      the Caatinga biome in northeastern Brazil. We used multiplex sets to amplify and
      genotype 30 individuals of P. diplolister from three different populations and 10
      individuals of P. alium from a single population. We successfully amplified 24
      loci for P. diplolister, 13 of which we were able to amplify in P. alium. All
      loci were polymorphic. Significant deviations from the Hardy-Weinberg equilibrium
      and the presence of null alleles were only consistently detected at one locus
      (Pleu9). These markers will enable the study of geographic genetic diversity and
      evolutionary processes in these two Caatinga endemics, and the inclusion of
      genetic data for conservation planning of the Caatinga biome. 

PMID- 24668635
TI  - Relationship between genetic polymorphisms in the DRD5 gene and paranoid
      schizophrenia in northern Han Chinese.
AB  - Dopamine (DA) has been implicated in the pathophysiol-ogy of several psychiatric
      disorders, including schizophrenia. Thus, genes related to the dopaminergic
      (DAergic) system are good candidate genes for schizophrenia. One of receptors of
      the DA receptor system is dopa-mine receptor 5 (DRD5). Single nucleotide
      polymorphisms (SNPs) in the regulatory regions of DRD5 gene may affect gene
      expression, influence biosynthesis of DA and underlie various neuropsychiatric
      disorders re-lated to DA dysfunction. The present study explored the association
      of SNPs within the DRD5 gene with paranoid schizophrenia in Han Chinese. A total
      of 176 patients with schizophrenia and 206 healthy controls were genotyped for
      four DRD5 SNPs (rs77434921, rs2076907, rs6283, and rs1800762). Significant group
      differences were observed in the allele and genotype frequencies of rs77434921
      and rs1800762 and in the frequen-cies of GC haplotypes corresponding to
      rs77434921-rs1800762. Our find-ings suggest that common genetic variations of
      DRD5 are likely to con-tribute to genetic susceptibility to paranoid
      schizophrenia in Han Chinese. Further studies in larger samples are needed to
      replicate this association. 

PMID- 24668636
TI  - Selection of sugar cane families by using BLUP and multi-diverse analyses for
      planting in the Brazilian savannah.
AB  - This study evaluated different strategies to select sugar cane families and
      obtain clones adapted to the conditions of the Brazilian savannah. Specifically,
      7 experiments were conducted, with 10 full sib families, and 2 witnesses in
      common to all experiments, in each experiment. The plants were grown in random
      blocks, with witnesses in common (incomplete blocks), and 6 repetitions of each
      experiment. The data were analyzed through the methodology of mixed patterns, in
      which the matrices of kinship between the families were identified by the method
      of restricted maximum likelihood. The characteristics that were evaluated
      included soluble solids content (BRIX), BRIX ton/ha, average mass of a culm,
      number of culms/m, and tons of culms/ha. A multi-diverse alternative based on the
      analysis of groupings by using the UPGMA method was used to identify the most
      viable families for selection, when considering the genotypic effects on all
      characteristics. This method appeared suitable for the selection of families,
      with 5 family groups being formed. The families that formed Group 2 appeared
      superior to all other families for all the evaluated characteristics. It is
      recommended that the families in Group 2 are preferentially used in sugar cane
      improvement programs to obtain varieties optimally adapted to the conditions of
      the Brazilian savannah. 

PMID- 24668637
TI  - Polymorphisms of the nucleolus organizing regions in Loricaria cataphracta
      (Siluriformes, Loricariidae) of the upper Paraguay River basin indicate an
      association with transposable elements.
AB  - A cytogenetic analysis of Loricaria cataphracta revealed a diploid number of 2n =
      64 chromosomes, distributed as 12 metacentric + 8 submetacentric + 2
      subtelocentric + 42 acrocentric, with a fundamental number of 86. Analysis of the
      nucleolus organizing region (NOR) using silver nitrate impregnation and
      fluorescence in situ hybridization (18S rDNA probe) techniques showed intra
      population chromosomal polymorphism that could be classified into five different
      patterns (I to V), involving four pairs of chromosomes (8, 9, 12, and 13). In
      pattern I, the NOR was located in pair 12, whereas in pattern II, the NOR was
      detected in pair 8; these two patterns were characterized as a simple-NOR system.
      A multiple NOR system was evident in the other patterns (III, IV, and V). In
      pattern III, the NOR was located in only one of the homologs of pairs 12 and 8,
      and in patterns IV and V, the NOR was observed in pair 12 and in only one of the
      homologs of pairs 9 and 13, respectively. In addition, C-band analysis also
      showed this pattern of variation, and characterized a polymorphism in relation to
      the constitutive heterochromatin; the composition of this region was GC-rich
      (positive CMA3) and 4',6-diamidino-2-phenylindole negative. Transposition of NOR
      sites for mobile elements is suggested to explain this polymorphism. 

PMID- 24668638
TI  - Ropivacaine via trans-cricothyroid membrane injection inhibits the extubation
      response in patients undergoing surgery for maxillary and mandibular fractures.
AB  - Extubation response can lead to cardiovascular and respiratory complications.
      Here, we aimed to evaluate the effect of ropivacaine injected via the trans
      cricothyroid membrane on the extubation response. This prospective, double-blind,
      randomized study included 70 patients classified as American Society of
      Anesthesiologists status I-II, who required general anesthesia with nasotracheal
      intubation for maxillary and mandibular fracture surgery; patients were divided
      into the ropivacaine (20 mg) and dicaine (20 mg) groups. Both groups were
      injected via the trans-cricothyroid membrane. Mean arterial pressure (MAP), heart
      rate (HR), and incidence and severity of cough were recorded during intubation
      and extubation. During intubation, there was no significant intergroup difference
      in MAP or HR and no occurrence of coughing (P > 0.05). During extubation, MAP and
      HR were significantly lower in the ropivacaine group than the dicaine group (P <
      0.05). The proportion of patients with no reports of cough was significantly
      higher in the ropivacaine group than in dicaine group (P < 0.05). The number of
      patients with grade 1 or 2 cough was significantly higher in the dicaine group
      than that in the ropivacaine group (P < 0.05). There was no significant
      intergroup difference in the rate of postoperative complications (P > 0.05).
      These results suggest that the administration of ropivacaine via trans
      cricothyroid membrane injection can effectively inhibit the extubation response. 

PMID- 24668639
TI  - Polymorphism analysis of IGFBP-5 gene exon 1 in Tibet Mini-pig and Junmu No. 1
      White pig.
AB  - The genetic resources and the mechanism of miniaturization in the Tibet Mini-pig
      have not been comprehensively studied. Polymorphisms in genes related to the
      insulin-like growth factor (IGF) axis have been investigated for years, but few
      on the polymorphism of IGF-binding protein-5 (IGFBP-5) in the Tibetan pig. In
      this study, allele-specific polymerase chain reaction (AS-PCR) was used to
      analyze polymorphisms in exon 1 of the IGFBP-5 gene in two pig breeds, Tibet Mini
      pigs and Junmu No. 1 White pigs. A BLAST analysis of the expressed sequence tags
      in the porcine IGFBP-5 gene revealed that exon 1 of this gene has two single
      nucleotide polymorphisms (SNPs), G188T and G503A. The AS-PCR results demonstrated
      that in both pig breeds examined, the TT, GT, and GG genotypes existed at the
      G188T locus, with GT as the most common genotype. At the G503A locus, GG, GA, and
      AA genotypes existed in Junmu No. 1 White pigs, with the GA genotype as the most
      frequently occurring. By contrast, at this locus, only the GA and AA genotypes
      were observed in the Tibetan pigs, and AA was more common than GA. There was a
      significant difference (P < 0.01) in allele distribution between the two breeds
      at the G503A locus but not the G188T locus, and there was a lower polymorphism
      information content for the two polymorphic loci in Tibet Mini-pigs than in Junmu
      No. 1 White pigs. The present study revealed SNPs in exon 1 of IGFBP-5 gene in
      the Tibet Mini-pig, possibly providing more understanding of the mechanism of
      miniaturization. 

PMID- 24668640
TI  - Tc-99m depreotide SPECT/CT for lymph node staging of non-small-cell lung cancer.
AB  - OBJECTIVE: To investigate the potential role of Tc-99m depreotide (Tc-DEPR) in
      the preoperative lymph node (N) staging of non-small-cell lung cancer (NSCLC).
      METHODS: Sixty-one patients with NSCLC at the potentially operable stage were
      enrolled and underwent scintigraphy before surgery (n=56) or mediastinoscopy
      (n=5). Imaging was performed with a hybrid single photon emission computed
      tomography/computed tomography (SPECT/CT) system. Depreotide uptake in N stations
      was evaluated visually and semi-quantitatively and compared to histology.
      Quantification was carried out in attenuation-corrected SPECT slices. Different
      sites of normal uptake were used as a reference for comparison with lesional
      uptake. Receiver operating characteristic analysis was employed to identify the
      most preferable reference area and the cut-off best discriminating disease-free
      from disease-involved lymph nodes. RESULTS: With reference to 53 Nu1 hilar and
      147 Nu2/Nu3 sampled stations, sensitivity of scintigraphy by visual
      interpretation was 100 and 94%, specificity 43 and 59% and accuracy 55 and 67%,
      respectively. No patient was down-staged, but 52% were incorrectly up-staged and
      44% were misclassified as inoperable. Compared to scintigraphy, preoperative
      contrast-enhanced diagnostic CT demonstrated lower sensitivity (36% for hilar and
      73% for N2/N3 stations), higher specificity (79 and 75%) and similar accuracy (70
      and 75%). Regarding the ultimate N-stage and the prediction of surgical disease,
      diagnostic CT was wrong in 51 and 34% of cases. Dichotomy of quantitative
      scintigraphic data by the use of certain N-to-spine ratio cut-offs resulted in a
      significant increase of specificity (76% for hilar and 89% for N2/N3 stations),
      while sensitivity remained high (82% in both circumstances) and accuracy for
      Nu2/Nu3 stations was substantially improved (88%). By this quantitative approach,
      misclassifications as to the N-stage and patient operability (25 and 16%) were
      considerably less than that of visual Tc-DEPR and diagnostic CT interpretations.
      CONCLUSION: Tc-99m depreotide SPECT/CT seems to have a role in the N-staging of
      NSCLC, mainly because of its high sensitivity and negative predictive value.
      Quantification of uptake can improve specificity, at a low cost of sensitivity.
      If F-18 fluoro-deoxyglucose positron emission tomography is not available, this
      method may be used as a surrogate to conventional staging modalities.

PMID- 24668641
TI  - Certain carotenoids enhance the intracellular glutathione level in a murine
      cultured macrophage cell line by inducing glutamate-cysteine-ligase.
AB  - SCOPE: Glutathione (GSH) increases in RAW264 murine macrophage cells exposed to
      beta-carotene or beta-cryptoxanthin, however, the underlying mechanism has not
      been clarified. In the present study, we investigated the expression of glutamate
      cysteine-ligase (GCL), the rate-limiting enzyme in GSH synthesis, in these cells.
      METHODS AND RESULTS: Both the protein and mRNA expression of GCL increased in a
      beta-carotene concentration-dependent manner. Buthionine sulfoximine, a GCL
      inhibitor, abolished the beta-carotene-induced GSH increase without affecting the
      beta-carotene-induced GCL protein expression. Both cycloheximide, a translation
      inhibitor, and actinomycin D, a transcription inhibitor, completely suppressed
      the beta-carotene-induced GCL protein expression and the concomitant GSH
      increase. Actinomycin D inhibited the beta-carotene-induced Gcl mRNA expression
      as well. Similarly to beta-carotene, beta-cryptoxanthin upregulated the GCL
      protein expression, but lutein did not. The c-Jun N-terminal kinase (JNK)
      inhibitor, SP600125, suppressed the beta-carotene-induced GSH increase, whereas a
      p38 mitogen-activated protein kinase inhibitor or an extracellular signal
      regulated kinase 1/2 inhibitor did not. The JNK inhibitor also suppressed the
      beta-carotene-induced GCL protein expression, and consistently beta-carotene
      induced JNK phosphorylation. CONCLUSION: These findings revealed that certain
      carotenoids induce the Gcl mRNA expression in RAW264 cells and subsequently the
      GCL protein expression, which concomitantly enhances the intracellular GSH level,
      in a JNK pathway-related manner.

PMID- 24668643
TI  - Attachment toward the informal caregiver and perception of the amount of support
      received after elective surgery.
AB  - This study investigated the relationship between attachment representations and
      help received from informal caregivers after elective surgery. In total, 98
      respondents reported on their attachment toward their informal caregiver before
      surgery and on the amount of help they received from the caregiver after surgery.
      We found that anxious attachment was negatively related to all types of support
      except for ensuring and explaining medical care, whereas avoidant attachment was
      negatively related to emotional types of support. This study extends previous
      findings by demonstrating the influence of attachment representations on help
      received in the context of the unique help provided after elective surgery. 

PMID- 24668642
TI  - Does fertility-specific distress vary by race/ethnicity among a probability
      sample of women in the United States?
AB  - This study explored whether fertility-specific distress varied by race/ethnicity
      among a nationally representative sample of US women. Participants were 2363
      White (n = 1266), Black (n = 569), Hispanic (n = 453), and Asian (n = 51) women
      who participated in the National Survey of Fertility Barriers. Participants were
      given the Fertility-Specific Distress Scale and assessed for strength of
      pregnancy intent, primary versus secondary infertility, and socioeconomic
      hardship. Black women reported lower levels of fertility-specific distress than
      White women, but these were fully mediated by the strength of pregnancy
      intentions. Primary versus secondary infertility and economic hardship were not
      associated with fertility-specific distress. 

PMID- 24668644
TI  - Clinical activity of adjuvant cytokine-induced killer cell immunotherapy in
      patients with post-mastectomy triple-negative breast cancer.
AB  - PURPOSE: Triple-negative breast cancer (TNBC) is a high risk form of this
      disease, even after surgery, due to the absence of targets for hormone treatment
      and anti-Her-2 therapy. Chemotherapy is the main therapeutic strategy for such
      patients with breast cancer, although the outcome is often unsatisfactory. Thus,
      the development of combination adjuvant therapies is essential for improved
      prognosis in patients with TNBC. In this study, we investigated the efficacy of a
      sequential combination of cytokine-induced killer cell (CIK) infusion and
      chemotherapy for patients with post-mastectomy TNBC. EXPERIMENTAL DESIGN: From
      2008 to 2012, 90 patients with post-mastectomy TNBC were included in this
      retrospective study: 45 cases received chemotherapy alone or with sequential
      radiotherapy; a further 45 cases received chemotherapy with/without radiotherapy
      and sequential CIK infusion. RESULTS: Survival analysis showed significantly
      higher disease-free survival (DFS) and overall survival (OS) rates in the CIK
      treatment group compared with the control group (P = 0.0382, P = 0.0046,
      respectively; log-rank test). Multivariate survival analysis showed that CIK
      adjuvant treatment was an independent prognostic factor for OS of patients with
      TNBC. In subgroup analyses, CIK adjuvant treatment significantly increased the
      DFS rate of patients with pathologic grade 3, and significantly increased the OS
      rate of patients in N1, N2, N3, IIB, III TNM (tumor-node-metastasis) stages, and
      with pathologic grade 3. CONCLUSIONS: These data indicate that adjuvant CIK
      treatment combined with chemotherapy is an effective therapeutic strategy to
      prevent disease recurrence and prolong survival of patients with TNBC,
      particularly those with lymph node metastasis, advanced TNM stage, and poor
      pathologic grade. Clin Cancer Res; 20(11); 3003-11. (c)2014 AACR.

PMID- 24668645
TI  - A surprising cross-species conservation in the genomic landscape of mouse and
      human oral cancer identifies a transcriptional signature predicting metastatic
      disease.
AB  - PURPOSE: Improved understanding of the molecular basis underlying oral squamous
      cell carcinoma (OSCC) aggressive growth has significant clinical implications.
      Herein, cross-species genomic comparison of carcinogen-induced murine and human
      OSCCs with indolent or metastatic growth yielded results with surprising
      translational relevance. EXPERIMENTAL DESIGN: Murine OSCC cell lines were
      subjected to next-generation sequencing (NGS) to define their mutational
      landscape, to define novel candidate cancer genes, and to assess for parallels
      with known drivers in human OSCC. Expression arrays identified a mouse metastasis
      signature, and we assessed its representation in four independent human datasets
      comprising 324 patients using weighted voting and gene set enrichment analysis.
      Kaplan-Meier analysis and multivariate Cox proportional hazards modeling were
      used to stratify outcomes. A quantitative real-time PCR assay based on the mouse
      signature coupled to a machine-learning algorithm was developed and used to
      stratify an independent set of 31 patients with respect to metastatic
      lymphadenopathy. RESULTS: NGS revealed conservation of human driver pathway
      mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase,
      phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative
      analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L,
      and MYH6 as novel putative cancer genes. Expression analysis identified a
      transcriptional signature predicting aggressiveness and clinical outcomes, which
      were validated in four independent human OSCC datasets. Finally, we harnessed the
      translational potential of this signature by creating a clinically feasible assay
      that stratified patients with OSCC with a 93.5% accuracy. CONCLUSIONS: These data
      demonstrate surprising cross-species genomic conservation that has translational
      relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873-84.
      (c)2014 AACR.

PMID- 24668646
TI  - Quantitative measurements of tumoral p95HER2 protein expression in metastatic
      breast cancer patients treated with trastuzumab: independent validation of the
      p95HER2 clinical cutoff.
AB  - PURPOSE: P95HER2 (p95) is a truncated form of the HER2, which lacks the
      trastuzumab-binding site and contains a hyperactive kinase domain. Previously, an
      optimal clinical cutoff of p95 expression for progression-free survival (PFS) and
      overall survival (OS) was defined using a quantitative VeraTag assay (Monogram
      Biosciences) in a training set of trastuzumab-treated metastatic breast cancer
      (MBC) patients. EXPERIMENTAL DESIGN: In the current study, the predictive value
      of the p95 VeraTag assay cutoff established in the training set was
      retrospectively validated for PFS and OS in an independent series of 240
      trastuzumab-treated MBC patients from multiple institutions. RESULTS: In the
      subset of 190 tumors assessed as HER2-total (H2T)-positive using the quantitative
      HERmark assay (Monogram Biosciences), p95 VeraTag values above the predefined
      cutoff correlated with shorter PFS (HR = 1.43; P = 0.039) and shorter OS (HR =
      1.94; P = 0.0055) where both outcomes were stratified by hormone receptor status
      and tumor grade. High p95 expression correlated with shorter PFS (HR = 2.41; P =
      0.0003) and OS (HR = 2.57; P = 0.0025) in the hormone receptor-positive subgroup
      of patients (N = 78), but not in the hormone receptor-negative group. In contrast
      with the quantitative p95 VeraTag measurements, p95 immunohistochemical
      expression using the same antibody was not significantly correlated with
      outcomes. CONCLUSIONS: The consistency in the p95 VeraTag cutoff across different
      cohorts of patients with MBC treated with trastuzumab justifies additional
      studies using blinded analyses in larger series of patients.

PMID- 24668647
TI  - Chimeric rat/human HER2 efficiently circumvents HER2 tolerance in cancer
      patients.
AB  - PURPOSE: Despite the great success of HER2 vaccine strategies in animal models,
      effective clinical results have not yet been obtained. We studied the feasibility
      of using DNA coding for chimeric rat/human HER2 as a tool to break the
      unresponsiveness of T cells from patients with HER2-overexpressing tumors (HER2
      CP). EXPERIMENTAL DESIGN: Dendritic cells (DCs) generated from patients with HER2
      overexpressing breast (n = 28) and pancreatic (n = 16) cancer were transfected
      with DNA plasmids that express human HER2 or heterologous rat sequences in
      separate plasmids or as chimeric constructs encoding rat/human HER2 fusion
      proteins and used to activate autologous T cells. Activation was evaluated by IFN
      gamma ELISPOT assay, perforin expression, and ability to halt HER2+ tumor growth
      in vivo. RESULTS: Specific sustained proliferation and IFN-gamma production by
      CD4 and CD8 T cells from HER2-CP was observed after stimulation with autologous
      DCs transfected with chimeric rat/human HER2 plasmids. Instead, T cells from
      healthy donors (n = 22) could be easily stimulated with autologous DCs
      transfected with any human, rat, or chimeric rat/human HER2 plasmid. Chimeric
      HER2-transfected DCs from HER2-CP were also able to induce a sustained T-cell
      response that significantly hindered the in vivo growth of HER2(+) tumors. The
      efficacy of chimeric plasmids in overcoming tumor-induced T-cell dysfunction
      relies on their ability to circumvent suppressor effects exerted by regulatory T
      cells (Treg) and/or interleukin (IL)-10 and TGF-beta1. CONCLUSIONS: These results
      provide the proof of concept that chimeric rat/human HER2 plasmids can be used as
      effective vaccines for any HER2-CP with the advantage of being not limited to
      specific MHC. Clin Cancer Res; 20(11); 2910-21. (c)2014 AACR.

PMID- 24668648
TI  - Alcohol dehydrogenase III exacerbates liver fibrosis by enhancing stellate cell
      activation and suppressing natural killer cells in mice.
AB  - The important roles of retinols and their metabolites have recently been
      emphasized in the interactions between hepatic stellate cells (HSCs) and natural
      killer (NK) cells. Nevertheless, the expression and role of retinol metabolizing
      enzyme in both cell types have yet to be clarified. Thus, we investigated the
      expression of retinol metabolizing enzyme and its role in liver fibrosis. Among
      several retinol metabolizing enzymes, only alcohol dehydrogenase (ADH) 3
      expression was detected in isolated HSCs and NK cells, whereas hepatocytes
      express all of them. In vitro treatment with 4-methylpyrazole (4-MP), a broad ADH
      inhibitor, or depletion of the ADH3 gene down-regulated collagen and transforming
      growth factor-beta1 (TGF-beta1) gene expression, but did not affect alpha-smooth
      muscle actin gene expression in cultured HSCs. Additionally, in vitro, treatments
      with retinol suppressed NK cell activities, whereas inhibition of ADH3 enhanced
      interferon-gamma (IFN-gamma) production and cytotoxicity of NK cells against
      HSCs. In vivo, genetic depletion of the ADH3 gene ameliorated bile duct ligation-
      and carbon tetrachloride-induced liver fibrosis, in which a higher number of
      apoptotic HSCs and an enhanced activation of NK cells were detected. Freshly
      isolated HSCs from ADH3-deficient mice showed reduced expression of collagen and
      TGF-beta1, but enhanced expression of IFN-gamma was detected in NK cells from
      these mice compared with those of control mice. Using reciprocal bone marrow
      transplantation of wild-type and ADH3-deficient mice, we demonstrated that ADH3
      deficiency in both HSCs and NK cells contributed to the suppressed liver
      fibrosis. CONCLUSION: ADH3 plays important roles in promoting liver fibrosis by
      enhancing HSC activation and inhibiting NK cell activity, and could be used as a
      potential therapeutic target for the treatment of liver fibrosis.

PMID- 24668649
TI  - Genipin-crosslinked gelatin-silk fibroin hydrogels for modulating the behaviour
      of pluripotent cells.
AB  - Different hydrogel materials have been prepared to investigate the effects of
      culture substrate on the behaviour of pluripotent cells. In particular, genipin
      crosslinked gelatin-silk fibroin hydrogels of different compositions have been
      prepared, physically characterized and used as substrates for the culture of
      pluripotent cells. Pluripotent cells cultured on hydrogels remained viable and
      proliferated. Gelatin and silk fibroin promoted the proliferation of cells in the
      short and long term, respectively. Moreover, cells cultured on genipin
      crosslinked gelatin-silk fibroin blended hydrogels were induced to an epithelial
      ectodermal differentiation fate, instead of the neural ectodermal fate obtained
      by culturing on tissue culture plates. This work confirms that specific culture
      substrates can be used to modulate the behaviour of pluripotent cells and that
      our genipin-crosslinked gelatin-silk fibroin blended hydrogels can induce
      pluripotent cells differentiation to an epithelial ectodermal fate. Copyright (c)
      2014 John Wiley & Sons, Ltd.

PMID- 24668650
TI  - Sequencing and phylogenetic analysis of the Pyrgilauda ruficollis (Aves,
      Passeridae) complete mitochondrial genome.
AB  - In this study, both long PCR and conserved primers walking sequencing methods
      were used to determine the complete sequence of the of Pyrgilauda ruficollis
      mitochondrial genome (KC836121). The results showed that the complete
      mitochondrial genome of P. ruficollis is 1 6909 bp in length with 55.0% A+T
      content, harboring the typical 37 genes. The mitogenome had the same gene order
      with that of Podoces hendersoni. All protein coding genes started with ATG codon,
      except ND3 with GTG. For the stop codon usage, most genes terminate with codons
      TAA or TAG, but ND5 terminated with AGA, while ND1 and COI genes with AGG, and
      both the genes COIII and ND4 have an incomplete termination codon (T). The
      secondary structures of 22 tRNA genes were also predicted, showing that all tRNAs
      can form typical clover-leaf secondary structures, except for the tRNA(Ser) (AGN)
      which loses the DHU arm, while tRNA(Phe) harbor an extra nucleotide inserted in
      the TpsiC arm. The predicted secondary structures of 12S rRNA and 16S rRNA
      exhibit 47 helices in 4 domains and 60 helices in 6 domains respectively. The
      control region of P. ruficollis with the length of 1 305 bp was located between
      tRNA(Glu) and tRNA(Phe), and typical domains of which could be found as other
      bird groups. Using the data from 13 mitochondrial protein-coding genes, results
      of a final phylogenetic analysis strongly supports the traditional view that P.
      ruficollis is closely related with Passeridae and Fringillidae.

PMID- 24668651
TI  - mRNA expression and DNA methylation in three key genes involved in caste
      differentiation in female honeybees (Apis mellifera).
AB  - In honeybee (Apis mellifera) colonies, queens and workers are alternative forms
      of the adult female honeybee that develop from genetically identical zygotes but
      that depend on differential nourishment. Queens and workers display distinct
      morphologies, anatomies and behavior, better known as caste differentiation.
      Despite some basic insights, the exact mechanism responsible for this phenomenon,
      especially at the molecular level, remains unclear although some progress has
      been achieved. In this study, we examined mRNA levels of the TOR (target of
      rapamycin) and Dnmt3 (DNA methyltransferase 3) genes, closely related to caste
      differentiation in honeybees. We also investigated mRNA expression of the S6K
      (similar to RPS6-p70-protein kinase) gene linked closely to organismal growth and
      development in queen and worker larvae (1-day and 3-day old). Last, we
      investigated the methylation status of these three genes in corresponding castes.
      We found no difference in mRNA expression for the three genes between 1st instar
      queen and worker larvae; however, 3rd instar queen larvae had a higher level of
      TOR mRNA than worker larvae. Methylation levels of all three genes were lower in
      queen larvae than worker larvae but the differences were not statistically
      significant. These findings provide basic data for broadening our understanding
      of caste differentiation in female honeybees. 

PMID- 24668652
TI  - Cloning the Dmrt1 and DmrtA2 genes of ayu (Plecoglossus altivelis) and mapping
      their expression in adult, larval, and embryonic stages.
AB  - The Dmrt family of genes are involved in sex differentiation in different species
      of invertebrates, and some vertebrates including human. In this study, we cloned
      the full-length cDNA of ayu (Plecoglossus altivelis) Dmrt1 and DmrtA2. Sequence
      and phylogenetic tree analyses showed ayu Dmrt1 showed highest similarity to that
      of Oncorhynchus mykiss while ayu DmrtA2 is most similar to that of Oryzias
      latipes. Fluorescence-based quantitative reverse transcription PCR (qRT-PCR)
      revealed the Dmrt1 was predominantly expressed in the testis. At the larval
      stages, Dmrt1 mRNA expression level was highest during 52-64 days post hatching
      (dph) and at the gastrula stage during embryonic development. DmrtA2, meanwhile,
      was specifically expressed in the ovary and was highly expressed in the female
      brain tissue, but not male brain tissue. During the larval stages, DmrtA2
      expression remained high before day 34, and then fluctuated while generally
      decreasing. During embryonic development, DmrtA2 expression increased gradually
      and peaked at the hatching stage. Our data suggest that ayu Dmrt1 might
      participate in the differentiation and maintenance of testis while DmrtA2 may
      play a role in ovary-differentiation and mature-ovary maintenance. DmrtA2 might
      also participate in brain development.

PMID- 24668653
TI  - Microsatellite analysis of variation among wild, domesticated, and genetically
      improved populations of blunt snout bream (Megalobrama amblycephala).
AB  - In the present study, the genetic diversity of one selected strain (Pujiang No.
      1), two domesticated populations (GA and HX) and four wild populations (LZ, YN,
      SS and JL) of blunt snout bream (Megalobrama amblycephala) was analyzed using 17
      microsatellite markers. The results showed that an average of 4.88-7.65 number of
      alleles (A); an average of 3.20-5.33 effective alleles (Ne); average observed
      heterozygosity (Ho) of 0.6985-0.9044; average expected heterozygosity (He) of
      0.6501-0.7805; and the average polymorphism information content (PIC) at 0.5706
      0.7226. Pairwise FST value between populations ranged from 0.0307-0.1451, and
      Nei's standard genetic distance between populations was 0.0938-0.4524. The
      expected heterozygosities in the domesticated populations (GA and HX) were
      significantly lower than those found in three wild populations (LZ, SS and JL),
      but no difference was detected when compared with the wild YN population.
      Likewise, no difference was found between the four wild populations or two
      domesticated populations. The expected heterozygosity in Pujiang No. 1 was higher
      than the two domesticated populations and lower than the four wild populations.
      Regarding pairwise FST value between populations, permutation test P-values were
      significant between the GA, HX and PJ populations, but not between the four wild
      populations. These results showed that the expected heterozygosity in the
      selected strain of blunt snout bream, after seven generations of selective
      breeding, was lower than that of wild populations, but this strain retains higher
      levels of genetic diversity than domesticated populations. The genetic
      differences and differentiation amongst wild populations, domesticated
      populations and the genetically improved strain of blunt snout bream will provide
      important conservation criteria and guide the utilization of germplasm resources.

PMID- 24668654
TI  - Effects of cold narcosis on memory acquisition, consolidation and retrieval in
      honeybees (Apis mellifera).
AB  - In learning and memory studies on honeybees (Apis mellifera), cold-induced
      narcosis has been widely used to temporarily immobilize honeybees. In this study,
      we investigated the effects of cold narcosis on the associative memories in
      honeybees by using the proboscis extension response (PER) paradigm. Severe
      impairments in memory acquisition was found when cold narcosis was performed 30
      min, instead of 1 h before training. Locomotor activities were reduced when
      honeybees were tested 15 min, instead of 30 min after cold narcosis. These
      results indicate that cold narcosis impairs locomotor activities, as well as
      memory acquisition in a time-dependent manner, but by comparison no such effects
      on memory retrieval have yet been observed.[0]. 

PMID- 24668655
TI  - Effects of hydroperiod duration on developmental plasticity in tiger frog
      (Hoplobatrachus chinensis) tadpoles.
AB  - While developmental plasticity can facilitate evolutionary diversification of
      organisms, the effects of water levels as an environmental pressure on tiger
      frogs remains unclear. This study clarifies the relationship by studying the
      responses of tiger frog (Hoplobatrachus chinensis) tadpoles to simulated
      hydroperiods (i.e., constant low water levels, constant high water levels,
      increasing water levels, decreasing water levels, rapid changes in water levels
      and gradual fluctuations in water levels) in a laboratory setting. ANOVA analysis
      showed that none of the water level treatments had any significant effect on the
      total length, body mass, or developmental stages of H. chinensis tadpoles half
      way through development (11 days old). Tadpoles raised in rapidly fluctuating
      water levels had protracted metamorphosis, whereas tadpoles raised under low and
      gradually fluctuating water levels had shortened metamorphosis. None of the water
      level treatments had a significant effect on the snout-vent length (SVL) or body
      mass of H. chinensis tadpoles at Gosner stage 42, or on the body mass of tadpoles
      at Gosner stage 45. However, the tadpoles raised in high levels and rapidly
      fluctuating water levels, significantly larger SVL at Gosner stage 45, while ones
      under gradually fluctuating water levels had smaller SVL than the other groups.
      Time to metamorphosis was positively correlated with body size (SVL) at
      metamorphosis in H. chinensis tadpoles. H. chinensis tadpoles under constant low
      water level had the highest mortality rate among all the treatments (G-test).
      Moreover, ANOVA and ACNOVA (with body length as the covariate) indicated that
      water levels had no significant effect on either the morphology (i.e. head
      length, head width, forelimb length, hindlimb length and body width) or the
      jumping ability of juvenile H. chinensis. These results suggest that the observed
      accelerated metamorphosis and high mortality of H. chinensis tadpoles under
      decreasing water level treatment was driven by density-induced physical
      interactions among increasing conspecifics. 

PMID- 24668656
TI  - Factors determining the average body size of geographically separated
      Arctodiaptomus salinus (Daday, 1885) populations.
AB  - Arctodiaptomus salinus inhabits water bodies across Eurasia and North Africa.
      Based on our own data and that from the literature, we analyzed the influences of
      several factors on the intra- and inter-population variability of this species. A
      strong negative linear correlation between temperature and average body size in
      the Crimean and African populations was found, in which the parameters might be
      influenced by salinity. Meanwhile, a significant negative correlation between
      female body size and the altitude of habitats was found by comparing body size in
      populations from different regions. Individuals from environments with highly
      varying abiotic parameters, e.g. temporary reservoirs, had a larger body size
      than individuals from permanent water bodies. The changes in average body mass in
      populations were at 11.4 times, whereas, those in individual metabolic activities
      were at 6.2 times. Moreover, two size groups of A. salinus in the Crimean and the
      Siberian lakes were observed. The ratio of female length to male length
      fluctuated between 1.02 and 1.30. The average size of A. salinus in populations
      and its variations were determined by both genetic and environmental factors.
      However, the parities of these factors were unequal in either spatial or temporal
      scales. 

PMID- 24668657
TI  - Taxonomical notes on selected freshwater fish species described from northern and
      central Vietnam (Cypriniformes: Balitoridae, Cobitidae, Cyprinidae,
      Nemacheilidae; Perciformes: Channidae, Osphronemidae; Synbranchiformes:
      Mastacembelidae).
AB  - Selected, little known taxa of northern and central Vietnamese freshwater fish
      species are reviewed. Nomenclatural acts are taken: Hemibarbus lehoai is placed
      in synonymy of H. maculatus, Paracobitis hagiangensis in synonymy of Schistura
      caudofurca. A neotype of Micronemacheilus bacmeensis is assigned. The name Channa
      hanamensis is treated as a nomen nudum. Two labeonine species described from
      China are nomenclaturally affected: Garra findolabium is transferred to Vinagarra
      and its specific epithet is treated as a noun in apposition; the specific epithet
      of Sinigarra napoense is corrected to napoensis.

PMID- 24668658
TI  - Modeling human cancer cachexia in colon 26 tumor-bearing adult mice.
AB  - BACKGROUND: Muscle wasting is a profound side effect of advanced cancer. Cancer
      induced cachexia decreases patient quality of life and is associated with poor
      patient survival. Currently, no clinical therapies exist to treat cancer-induced
      muscle wasting. Although cancers commonly associated with cachexia occur in older
      individuals, the standard animal models used to elucidate the causes of cachexia
      rely on juvenile mice. METHODS: In an effort to better model human cancer
      cachexia, we determined whether cachectic features seen in young mice could be
      achieved in adult, pre-sarcopenic mice following colon 26 (C-26) tumor cell
      inoculation. RESULTS: Both young and adult mice developed similar-sized tumors
      and progressed to cachexia with similar kinetics, as evidenced by losses in body
      mass, and adipose and skeletal muscle tissues. Proteolytic signaling, including
      proteasome and autophagy genes, was also increased in muscles from both young and
      adult tumor-bearing animals. Furthermore, tumor-associated muscle damage and
      activation of Pax7 progenitor cells was induced in both young and adult mice.
      CONCLUSIONS: Although cancer cachexia generally occurs in older individuals,
      these data suggest that the phenotype and underlying mechanisms can be
      effectively modeled using the currently accepted protocol in juvenile mice.

PMID- 24668659
TI  - Skeletal dysplasia, global developmental delay, and multiple congenital anomalies
      in a 5-year-old boy-report of the second family with B3GAT3 mutation and
      expansion of the phenotype.
AB  - As a major component of the extracellular matrix, proteoglycans influence the
      mechanical properties of connective tissue and play an important role in cell
      cell and cell-matrix interactions. Genetic defects of proteoglycan biosynthesis
      lead to multi-system disorders, often most prominently affecting the skeletal
      system and skin. Specific deficiencies in the enzymes involved in the
      biosynthesis of the linkage region between the core of the proteoglycan protein
      and its glycosaminoglycan side chains are known as linkeropathies. We report on a
      patient from a second family with a homozygous c.830G>A (p.Arg277Gln) mutation in
      the B3GAT3 gene. The clinical features expand the previously reported phenotype
      of B3GAT3 mutations and of linkeropathies in general. This patient has short
      stature, facial dysmorphisms, skeletal findings, joint laxity, and cardiac
      manifestations similar to those previously associated with B3GAT3 mutations.
      However, he also has developmental delay, a refractive errors, dental defects,
      pectus carinatum, and skin abnormalities that have only been associated with
      linkeropathies caused by mutations in B4GALT6 and B4GALT7. He has bilateral
      inguinal hernias and atlanto-axial as well as atlanto-occipital instability that
      have not been previously associated with B3GAT3 mutations. We provide a detailed
      clinical report and a comparative overview of the phenotypic features of the
      linkeropathies caused by mutations in B3GAT3, B4GALT6, and B4GALT7.

PMID- 24668660
TI  - Population pharmacokinetics and pharmacodynamics of rivaroxaban in patients with
      non-valvular atrial fibrillation: results from ROCKET AF.
AB  - Two once-daily rivaroxaban dosing regimens were compared with warfarin for stroke
      prevention in patients with non-valvular atrial fibrillation in ROCKET AF: 20 mg
      for patients with normal/mildly impaired renal function and 15 mg for patients
      with moderate renal impairment. Rivaroxaban population pharmacokinetic
      (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are
      reported and are used to confirm established rivaroxaban PK and PK/PD models and
      to re-estimate values of the models' parameters for the current AF population. An
      oral one-compartment model with first-order absorption adequately described
      rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model.
      Prothrombin time and prothrombinase-induced clotting time exhibited a near-linear
      relationship with rivaroxaban plasma concentration; inhibitory effects were
      observed through to 24 hours post-dose. Rivaroxaban plasma concentration and
      factor Xa activity had an inhibitory maximum-effect (Emax ) relationship. Renal
      function (on prothrombin time; prothrombinase-induced clotting time) and age (on
      factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models
      were shown to be adequate for describing the current dataset. These findings
      confirm the modeling and empirical results that led to the selection of doses
      tested against warfarin in ROCKET AF. 

PMID- 24668661
TI  - Application of Tensegrity Massage to Relive Complications After Mastectomy--Case
      Report.
AB  - PURPOSE: The case study was to determine the effectiveness of tensegrity massage
      in a patient after mastectomy. DESIGN: Tensegrity massage was performed in a 50
      year-old woman after mastectomy. The purpose of the massage was to normalize the
      tension of musculo-ligamento-fascial system in the chest, shoulder girdle, and
      back. METHODS: The patient was subjected to a series of six massage sessions, 45
      minutes each, twice a week. FINDINGS: The applied massage therapy contributed to
      the reduction of the postoperative scar tenderness and painfulness, to the
      relaxation of the muscular tone within the shoulder girdle, and to the
      improvement of the patient's general feeling. CONCLUSIONS: Tensegrity massage is
      an effective therapy in the elimination of pain and abnormal tissue tension
      induced by extensive scarring after mastectomy. CLINICAL RELEVANCE: The presented
      massage procedure had a positive effect immediately after the therapy and after 1
      month follow-up.

PMID- 24668662
TI  - Embolus-carried vascular endothelial cell growth factor 165 improves angiogenesis
      in thromboangiitis obliterans.
AB  - We investigated neovasculization effects of embolus-carried human vascular
      endothelial cell growth factor 165 (VEGF165)-encoded adenovirus (Ad) vector in
      the hindlimbs of rats with thromboangiitis obliterans (TAO). Rats were equally
      divided into blank control (I), TAO model (II), embolus (III), Ad-VEGF165
      intravascular treatment (IV), Ad-VEGF165 intramuscular treatment (V), and embolus
      carried Ad-VEGF165 (VI) groups. After interventional treatment, the
      neovasculization effect of the test gene was observed using immunohistochemistry.
      At 1 week after administration, compared with group II, groups V and VI had
      significantly increased microvessel densities, but no significant difference was
      observed between groups V and VI. At 2 weeks, groups V and VI exhibited
      significantly increased microvessel densities. At 1 week after administration,
      compared with group II, both groups V and VI showed a significant difference in
      the ratio between the alpha-smooth muscle actin count and the muscle fiber count,
      whereas no significant difference was observed between them. At 2 weeks, groups V
      and VI also exhibited significant differences in these ratios compared with the
      other groups. We conclude that Ad-VEGF165 promotes neovasculization in ischemic
      limbs. Embolus-carried Ad- VEGF165 had the most pronounced effect. 

PMID- 24668663
TI  - Dephosphorylation of NSSR1 regulates alternative splicing of the GluR-B minigene.
AB  - Neural salient serine/arginine-rich protein 1 (NSSR1, alternatively SRp38) is an
      important splicing factor that can repress pre-mRNA alternative splicing in cells
      during heat shock and mitosis. We show here that NSSR1 protein is
      dephosphorylated when cells are heat shocked or incubated with kinase inhibitor
      K252a. Both heat shock and K252a treatment increase the truncated splicing
      isoform of the GluR-B minigene pre-mRNA. We also investigated the roles of the
      RRM motif and three RS domains of NSSR1 in in vivo pre-mRNA splicing. The results
      show that deletion of the RRM motif did not affect GluR-B minigene pre-mRNA
      splicing, but deletion of any one of the three RS domains increases the truncated
      splicing isoform of the GluR-B minigene. We further show that an SRSRSK sequence
      in the RS3 domain may play an important role in the function of NSSR1 in pre-mRNA
      splicing. 

PMID- 24668664
TI  - Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down
      syndrome in China.
AB  - We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase
      (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism,
      affect maternal risk for Down syndrome. We investigated 76 Down syndrome mothers
      and 115 control mothers from Bengbu, China. Genomic DNA was isolated from the
      peripheral lymphocytes. Polymerase chain reaction and restriction fragment length
      polymorphism were used to examine the polymorphisms of MTHFD G1958A and TC C776G.
      The frequencies of the polymorphic alleles were 24.3 and 19.1% for MTHFD 1958A,
      53.9 and 54.2% for TC 776G, in the case and control groups, respectively. No
      significant differences were found between two groups in relation to either the
      allele or the genotype frequency for both polymorphisms. However, when gene-gene
      interactions between these two polymorphisms together with previous studied C677T
      and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene
      were analyzed, the combined MTHFR 677CT/TT and MTHFD 1958AA/GA genotype was found
      to be significantly associated with the risk of having a Down syndrome child
      [odds ratio (OR) = 3.11; 95% confidence interval (95%CI) = 1.07-9.02]. In
      addition, the combined TC 776CG and MTHFR 677TT genotype increased the risk of
      having a child with Down syndrome 3.64-fold (OR = 3.64; 95%CI = 1.28-10.31). In
      conclusion, neither MTHFD G1958A nor TC C776G polymorphisms are an independent
      risk factor for Down syndrome. However, the combined MTHFD/MTHFR, TC/MTHFR
      genotypes play a role in the risk of bearing a Down syndrome child in the Chinese
      population. 

PMID- 24668665
TI  - Higher frequency of CD4(+)CD25(high) Treg cells in hemophilia patients with
      factor VIII inhibitor.
AB  - The production of factor VIII inhibitor antibodies remains the most costly and
      serious complication in replacement therapy of hemophilia A. We investigated the
      clinical significance of CD4(+)CD25(high) T regulatory (Treg) cells in hemophilia
      patients. Our trial included 6 severe hemophilia A patients with factor VIII
      inhibitors, 6 hemophilia patients without inhibition of factor VIII, and 6
      healthy persons (controls). Plasma factor VIII: c was measured by clotting assay.
      Peripheral blood samples were examined using mutiparameter flow cytometry with
      fluorescent-labeled monoclonal antibodies. Plasma levels of IFN-gamma, IL-2, IL
      10, and TGF-beta were measured by ELISA. The frequency of CD4(+)CD25(high) Treg
      cells in CD4(+) cells was 1.07 +/- 0.38% in inhibitor patients and 0.57 +/- 0.14%
      in non-inhibitor patients. The proportion of Treg cells in healthy controls was
      similar to that of the non-inhibitor patients. However, there were significant
      differences between the inhibitor and non-inhibitor patients in levels of IFN
      gamma, IL-2, IL-10, and TGF-beta. We conclude that the proportions of Treg cells
      and the concentrations of T cell cytokines in inhibitor patients are higher than
      those in non-inhibitor patients. The increased number of Treg cells and increased
      T-cell cytokines may be related to the development and efficiency of the factor
      VIII inhibitor. 

PMID- 24668666
TI  - Statistical analyses of conserved features of genomic islands in bacteria.
AB  - We performed statistical analyses of five conserved features of genomic islands
      of bacteria. Analyses were made based on 104 known genomic islands, which were
      identified by comparative methods. Four of these features include sequence size,
      abnormal G+C content, flanking tRNA gene, and embedded mobility gene, which are
      frequently investigated. One relatively new feature, G+C homogeneity, was also
      investigated. Among the 104 known genomic islands, 88.5% were found to fall in
      the typical length of 10-200 kb and 80.8% had G+C deviations with absolute values
      larger than 2%. For the 88 genomic islands whose hosts have been sequenced and
      annotated, 52.3% of them were found to have flanking tRNA genes and 64.7% had
      embedded mobility genes. For the homogeneity feature, 85% had an h homogeneity
      index less than 0.1, indicating that their G+C content is relatively uniform.
      Taking all the five features into account, 87.5% of 88 genomic islands had three
      of them. Only one genomic island had only one conserved feature and none of the
      genomic islands had zero features. These statistical results should help to
      understand the general structure of known genomic islands. We found that larger
      genomic islands tend to have relatively small G+C deviations relative to absolute
      values. For example, the absolute G+C deviations of 9 genomic islands longer than
      100,000 bp were all less than 5%. This is a novel but reasonable result given
      that larger genomic islands should have greater restrictions in their G+C
      contents, in order to maintain the stable G+C content of the recipient genome. 

PMID- 24668667
TI  - Whole exome sequencing implicates PTCH1 and COL17A1 genes in ossification of the
      posterior longitudinal ligament of the cervical spine in Chinese patients.
AB  - Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine
      is a complex multifactorial disease. Patients with OPLL commonly present with
      symptoms in their 40s or 50s. The genetic basis of OPLL remains poorly
      understood. Exome capture combined with massively parallel DNA sequencing has
      been proposed as an efficient strategy to search for disease-causing genes of
      both monogenic and multigenic disorders. To identify candidate pathogenic genes
      associated with OPLL, we performed whole exome sequencing (WES) on two unrelated
      southern Chinese OPLL patients. The entire DNA coding region of the candidate
      genes was amplified by PCR and Sanger sequenced. The common single nucleotide
      polymorphisms were analyzed by association studies. WES revealed p.T265S/PTCH1,
      p.P1232L/PTCH1, and p.T902S/COL17A1 mutants in the two female cases with mixed
      OPLL. These were confirmed by Sanger sequencing. p.P1232L/PTCH1, p.N1374D/COL17A1
      and p.T902S/COL17A1 were subsequently identified in three males with continuous
      OPLL and one female with mixed OPLL. The association studies indicated that the
      SNPs rs805698 and rs4918079 in COL17A1 were significantly associated with OPLL.
      This study suggests that WES may be a practical approach to revealing significant
      genetic involvement in OPLL. Variants of the PTCH1 and COL17A1 genes may
      contribute to the development of OPLL. 

PMID- 24668668
TI  - Polymorphisms in the bone morphogenetic protein 15 gene and their effect on sperm
      quality traits in Chinese Holstein bulls.
AB  - Bone morphogenetic protein 15 (BMP-15) expression has been detected in the
      testis, but its roles in this organ has not been well elucidated. We evaluated
      polymorphisms of the BMP-15 gene by PCR-SSCP and PCR-RFLP in 212 Chinese Holstein
      bulls, and investigated possible associations with sperm quality traits,
      including semen volume per ejaculate, sperm density, fresh sperm motility, thawed
      sperm motility, acrosome integrity rate, and abnormal sperm rate. A single
      nucleotide polymorphism (C5697T) in intron 1 of the BMP-15 gene was identified in
      these bulls. Age was found to have significant effects on both fresh sperm
      motility and abnormal sperm rate. A significant effect of genotype on fresh sperm
      motility was also observed. Least square analysis showed that CT genotype bulls
      had significantly lower fresh sperm motility than CC or TT genotype bulls. In
      conclusion, BMP-15 should be considered as a potential genetic marker for sperm
      quality, based on its association with fresh sperm motility. 

PMID- 24668669
TI  - KIR gene polymorphism study in the Uygur population in Xinjiang, China.
AB  - We analyzed killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and
      genotype and haplotype characteristics in the Uygur population, a non-nomadic
      ethnic group found in Xinjiang, China, to provide a basis for studies on
      relationships between KIRs and diseases in this group. Sequence-specific primer
      PCR was used to detect the KIR gene in 84 Uygur individuals. A standard genotype
      and haplotype analysis was conducted using Hsu's standards. Sixteen KIR genes
      were detected; the 3DL3, 2DL4, 3DL2 genes were found in all individuals. The
      2DL1, 3DP1, 2DP1, 2DL3 genes were relatively common, followed by 2DS4, 3DL1,
      2DL5, 2DS2, 2DL2, 2DS1, 2DS5, and 3DS1. The 2DS3 gene had the lowest frequency. A
      total of 19 genotypes were detected, the AJ (2,2), AH (5,2) and M (2,8) genotypes
      were relatively common, with frequencies of 25, 10.7 and 10.7%, respectively;
      they were followed by P (2,17), AI (1,5), H (2,4), and C (5,3), with frequencies
      of 9.52, 5.95, 5.95, and 4.76%, respectively. The U (17,21), and T (8,8)
      genotypes, found in four individuals, had not been reported in the Han Chinese
      population. Eleven haplotypes were detected; the most common haplotype 2 (N = 74)
      was accounting for 48.7%, followed by haplotype 5 (N = 24), accounting for 15.8%.
      In addition, three new genotypes were found, for which haplotype analysis could
      not be performed based on existing standards. We conclude that the Xinjiang Uygur
      population has unique KIR gene frequency, genotype frequency and haplotype
      frequency distributions; there also appears to be new genotypes and haplotypes in
      this population.

PMID- 24668670
TI  - Module function and two-way clustering analysis of Epstein-Barr virus-related
      nasopharyngeal cancer.
AB  - This study sought to identify and characterize the function of genes as
      diagnostic markers for Epstein-Barr virus (EBV)-related nasopharyngeal cancer
      (NPC). The gene expression profile of GSE13597 was downloaded from the Gene
      Expression Omnibus database, which included 28 EBV-related NPC gene expression
      profile data sets, 25 disease samples, and 3 control samples. Data were pre
      processed, and differentially expressed genes were screened using the R language.
      The co-expression coefficient was calculated to construct a co-expression network
      using Cytoscape. ClusterONE was used to perform module analysis to find enriched
      gene families. The BiCAT software was used to perform a two-way clustering
      analysis of differentially expressed gene expression profiles based on the co
      expression networks and to verify the enriched gene families, followed by
      functional enrichment analysis of these gene families. The MCM gene family was
      found to be enriched in EBV-related NPC. This gene family is essential for
      eukaryotic DNA replication. Functional analysis of differentially expressed genes
      in the co-expression network revealed that the enriched biological processes and
      pathways were mainly involved in the cell cycle. EBV-related NPC is likely
      associated mainly with the process of cell reproduction, providing a strong basis
      for the prevention, diagnosis, and treatment of EBV-related NPC and a direction
      for targeted chemotherapy. 

PMID- 24668671
TI  - Molecular cloning and characterization of the pseudorabies virus UL31 gene.
AB  - We amplified a 816-bp sequence of the UL31 gene from the pseudorabies virus (PRV)
      Becker strain genome. Evidence that this was the UL31 gene was confirmed by
      cloning and sequencing. The PRV UL31 gene encodes a putative protein of 271-amino
      acid residues, which was designated the UL31 protein. Bioinformatic analysis
      indicated that PRV UL31 contains a conserved PHA03328 domain, closely related
      with the herpes virus nuclear egress lamina protein UL31 family and highly
      conserved among counterparts encoded by herpes UL31 genes. Nucleic acid sequence
      and amino acid sequence alignments demonstrated that PRV UL31 has a relatively
      higher homology with UL31 homologous proteins of subfamily Alphaherpesvirinae
      than other subfamilies. In addition, phylogenetic analysis showed that PRV UL31
      has a close evolutionary relationship with members of the subfamily
      Alphaherpesvirinae, especially bovine herpesvirus 1 (BoHV-1), BoHV-5, equine
      herpesvirus 4 (EHV-4), EHV-9 and EHV-1. Antigen prediction demonstrated that
      several potential B-cell epitopes are located in PRV UL31. Additionally,
      secondary structure and three-dimension structure prediction revealed that PRV
      UL31 predominantly consists of alpha-helix. Taken together, these results provide
      insight on the function and mechanism of UL31 during PRV infection. 

PMID- 24668672
TI  - Sperm retrieval from patients with nonmosaic Klinefelter's syndrome by semen
      cytology examination.
AB  - Successful sperm retrieval from ejaculates of nonmosaic Klinefelter's syndrome
      (KS) patients by using semen cytology examination was described in this report.
      The clinical parameters of KS patients with sperm compared to patients without
      sperm were described. One hundred and fifty-one patients were proven to suffer
      from KS by chromosomal analysis using G-banding. Spermatozoa were obtained from
      10 patients (10/151, 6.6%) using semen analysis. After semen cytology
      examination, 32 patients (32/151, 21.2%) were found to have sperm or germ cell in
      their ejaculate. The patients with successful sperm retrieval were significantly
      younger (27.1 +/- 3.7 years) than the patients for whom sperm retrieval failed
      (28.9 +/- 4.2 years). The mean serum testosterone level and the mean T/LH ratio
      of KS patients with successful sperm retrieval were significantly higher in men
      with sperm than in men without sperm (testosterone: 3.2 +/- 2.1 ng/mL vs 2.7 +/-
      1.5 ng/mL; T/LH ratio: 0.2 +/- 0.3 vs 0.1 +/- 0.1). In conclusion, semen cytology
      examination should be performed to identify sperm and germ cells in the ejaculate
      of KS patients if no sperm can be detected by traditional semen analysis. The
      serum testosterone level and T/LH ratio revealed an association between impaired
      Leydig cell function and impaired spermatogenesis in KS males. KS patients should
      receive earlier diagnosis and treatment. 

PMID- 24668673
TI  - Screening of differentially expressed genes between multiple trauma patients with
      and without sepsis.
AB  - The purpose of this study was to identify critical genes associated with septic
      multiple trauma by comparing peripheral whole blood samples from multiple trauma
      patients with and without sepsis. A microarray data set was downloaded from the
      Gene Expression Omnibus (GEO) database. This data set included 70 samples, 36
      from multiple trauma patients with sepsis and 34 from multiple trauma patients
      without sepsis (as a control set). The data were preprocessed, and differentially
      expressed genes (DEGs) were then screened for using packages of the R language.
      Functional analysis of DEGs was performed with DAVID. Interaction networks were
      then established for the most up- and down-regulated genes using HitPredict.
      Pathway-enrichment analysis was conducted for genes in the networks using
      WebGestalt. Fifty-eight DEGs were identified. The expression levels of PLAU (down
      regulated) and MMP8 (up-regulated) presented the largest fold-changes, and
      interaction networks were established for these genes. Further analysis revealed
      that PLAT (plasminogen activator, tissue) and SERPINF2 (serpin peptidase
      inhibitor, clade F, member 2), which interact with PLAU, play important roles in
      the pathway of the component and coagulation cascade. We hypothesize that PLAU is
      a major regulator of the component and coagulation cascade, and down-regulation
      of PLAU results in dysfunction of the pathway, causing sepsis. 

PMID- 24668674
TI  - Cloning and expression analysis of heat-shock transcription factor gene CaHsfA2
      from pepper (Capsicum annuum L.).
AB  - The heat-shock transcription factor (Hsf) gene CaHsfA2 (GenBank accession No.
      JX402923) was cloned from the Capsicum annuum thermotolerant line R9 by combining
      the techniques electron cloning and rapid amplification of cDNA ends. The gene,
      which is 1436 bp in length, had an open reading frame of 1089 bp that encoded 362
      amino acids. There was an 831-bp intron between positions 321 and 322 of the
      cDNA. The deduced amino acid sequence of CaHsfA2 contained the conserved domains
      of Hsf, including DNA binding domain, adjacent domain with heptad hydrophobic
      repeats (A/B), activator motifs, nuclear localization signal, and nuclear export
      signal, and it had the highest E value of hypothesized annotation of HsfA2.
      CaHsfA2 had the nearest phylogenetic relationship with HsfA2 from Lycopersicon
      peruvianum and Mimulus guttatus, which was consistent with its botanical
      classification. After heat-shock treatment at 40 degrees C for 2 h, the
      expression of CaHsfA2 was observed in different tissues of thermotolerant
      cultivar R9 and thermosensitive line B6; however, the expression levels of the
      CaHsfA2 gene were significantly different as follows: expression in B6 leaf >
      stem > flower > root, and expression in R9 flower > leaf > stem ~ root. 

PMID- 24668675
TI  - Investigation of the association of two candidate genes (H-FABP and PSMC1) with
      growth and carcass traits in Qinchuan beef cattle from China.
AB  - Growth and carcass traits are economically important quality characteristics of
      beef cattle and are complex quantitative traits that are controlled by multiple
      genes. In this study, 2 candidate genes, H-FABP (encoding the heart fatty acid
      binding protein) and PSMC1 (encoding the proteasome 26S subunit of ATPase 1) were
      investigated in Qinchuan beef cattle of China. PCR-SSCP and DNA sequencing
      methods were used to detect mutations in the H-FABP and PSMC1 genes in Qinchuan
      cattle, and a T>C mutation in exon 1 of H-FABP and a T>C mutation in exon 9 of
      PSMC1 were identified. The association of these 2 single nucleotide polymorphisms
      with growth and carcass traits of Qinchuan cattle was analyzed. The T>C mutation
      in H-FABP was significantly associated with body length and dressing percentage
      (P < 0.05) and the T>C mutation in PSMC1 with body length and hip width (P <
      0.05), indicating that both of the 2 mutations in H-FABP and PSMC1 had effects on
      growth and carcass traits in the Qinchuan beef cattle breed. Thus, the results of
      our study suggest that the H-FABP and PSMC1 gene polymorphisms could be used as
      genetic markers in marker-assisted selection for improving Qinchuan beef cattle. 

PMID- 24668676
TI  - Stable transfection and identification of a hair follicle-specific expression
      vector of IGFBP-5 in goat fetal fibroblasts.
AB  - The insulin-like growth factor-binding protein-5 (IGFBP-5) is one of the 6
      members of the IGFBP family and is involved in the regulation of cell growth,
      apoptosis, and other IGF-stimulated signaling pathways. To determine the
      significance of IGFBP-5 in the Inner Mongolia Cashmere goat (Capra hircus), a
      hair follicle-specific expression vector of IGFBP-5, pCDsRed2-K-IGFBP5 (6.7 kb),
      was constructed by cloning IGFBP-5 downstream of the keratin-association protein
      (KAP)6-1 promoter and inserting this fragment into pCDsRed2, which contains a red
      fluorescent protein (DsRed) expression unit. Inner Mongolia Cashmere goat fetal
      fibroblast (GFb) cells were transfected with the expression vector by using
      Lipofectamine(TM) 2000. Cell clones that stably expressed red fluorescence were
      obtained after selection with Geneticin (G418). The transgene in the cell clones
      was examined by polymerase chain reaction to verify that exogenous DNA (pKAP6-1
      and IGFBP-5) had integrated stably into GFb cells. These data suggest that this
      method can be used for the construction of a hair follicle-specific expression
      vector for functional genetic analyses and for obtaining stable transfection
      donor cells for nuclear transfer. 

PMID- 24668677
TI  - Characterization of the beta-1,3-glucanase gene in peanut (Arachis hypogaea L.)
      by cloning and genetic transformation.
AB  - Plant beta-1,3-glucanases are commonly involved in disease resistance. This
      report describes the cloning and genetic transformation of a beta-1,3-glucanase
      gene from peanut. The gene was isolated from both the genomic DNA and cDNA of
      peanut variety Huayu20 by polymerase chain reaction (PCR) and reverse
      transcription PCR (RT-PCR), respectively. The DNA sequence contained 1471 bp
      including two exons and one intron, and the coding sequence contained 1047 bp
      that coded for a 348-amino acid protein with a calculated molecular weight of
      38.8 kDa. The sequence was registered in NCBI (GenBank accession No. JQ801335)
      and was designated as Ah-Glu. As determined by BLAST analysis, the Ah-Glu protein
      has 42-90% homology with proteins from Oryza sativa (BAC83070.1), Zea mays
      (NP_001149308), Arabidopsis thaliana (NP_200470.1), Medicago sativa (ABD91577.1),
      and Glycine max (XP_003530515.1). The over-expression vector pCAMBIA1301-Glu
      containing Ah-Glu was constructed, confirmed by PCR and restriction enzyme
      digestion, and transformed into peanut variety Huayu22 by Agrobacterium EHA105
      mediated transformation. The putative transformed plants (T0) were confirmed by
      PCR amplification. RT-PCR analysis and beta-glucuronidase (GUS) staining showed
      that the transferred Ah-Glu was expressed as mRNA and protein. In a laboratory
      test, the transgenic plants were found to be more resistant to the fungal
      pathogen Cercospora personata than the non-transgenic plants were. 

PMID- 24668678
TI  - Isolation and characterization of polymorphic microsatellite loci of the Chinese
      muntjac (Muntiacus reevesi).
AB  - Eight polymorphic microsatellite markers for Muntiacus reevesi were identified
      and characterized in this study. The number of alleles per locus ranged from 3 to
      10 across 24-48 samples. The loci showed expected and observed heterozygosities
      of 0.577-0.876 and 0.387-0.933, respectively, with an average polymorphic
      information content value of 0.682. These markers should be a useful tool for
      further population and conservation genetic studies of Muntiacus reevesi. 

PMID- 24668679
TI  - Genetic relationship between lodging and lodging components in barley (Hordeum
      vulgare) based on unconditional and conditional quantitative trait locus
      analyses.
AB  - Lodging (LD) is a major constraint limiting the yield and forage quality of
      barley. Detailed analyses of LD component (LDC) traits were conducted using 246
      F2 plants generated from a cross between cultivars ZQ320 and 1277. Genetic
      relationships between LD and LDC were evaluated by unconditional and conditional
      quantitative trait locus (QTL) mapping with 117 simple sequence repeat markers.
      Ultimately, 53 unconditional QTL related to LD were identified on seven barley
      chromosomes. Up to 15 QTL accounted for over 10% of the phenotypic variation, and
      up to 20 QTL for culm strength were detected. Six QTL with pleiotropic effects
      showing significant negative correlations with LD were found between markers
      Bmag353 and GBM1482 on chromosome 4H. These alleles and alleles of QTL for wall
      thickness, culm strength, plant height, and plant weight originated from ZQ320.
      Conditional mapping identified 96 additional QTL for LD. Conditional QTL analysis
      demonstrated that plant height, plant height center of gravity, and length of the
      sixth internode had the greatest contribution to LD, whereas culm strength and
      length of the fourth internode, and culm strength of the second internode were
      the key factors for LD-resistant. Therefore, lodging resistance in barley can be
      improved based on selection of alleles affecting culm strength, wall thickness,
      plant height, and plant weight. The conditional QTL mapping method can be used to
      evaluate possible genetic relationships between LD and LDC while efficiently and
      precisely determining counteracting QTL, which will help in understanding the
      genetic basis of LD in barley. 

PMID- 24668681
TI  - Genomic changes at the early stage of somatic hybridization.
AB  - A broad spectrum of genetic and epigenetic changes is induced by wide
      hybridization and subsequent polyploidization, but the timing of these events
      remains obscure because early hybrid cells are very difficult to harvest and
      analyze. Here, we used both cytological and genetic marker approaches to analyze
      the constitution of very young somatic hybrid cells between japonica rice (Oryza
      sativa L. subsp japonica) and indica rice (Oryza sativa L. subsp indica) and
      between japonica rice and bread wheat (Triticum aestivum L.). Chromatin
      elimination, simple sequence repeats, and retrotransposon profile deletions were
      already apparent within six days of the fusion event. The evidence we have
      presented suggests that genomic changes induced by genomic shock occur soon after
      the formation of hybrid cells. 

PMID- 24668680
TI  - Molecular cloning, expression, and regulation of estrogen receptors in pigeon
      oviduct epithelial cells.
AB  - Estrogen regulates reproductive behavior and drives the proliferation and
      differentiation of several cell types. These physiological functions of estrogen
      are mediated by estrogen receptors (ERs), and each ER isoform plays a distinct
      role. To clarify the molecular mechanism of estrogen action and to evaluate the
      effect of ERs on the secretion of ovalbumin (OVA) in pigeon oviduct epithelial
      cells (POECs), we determined the complete coding sequences encoding ER alpha
      (ERalpha) and ER beta (ERbeta) in pigeons. The abundance of pigeon ERalpha and
      ERbeta mRNA was detected using quantitative polymerase chain reaction. These
      results revealed that pigeon ERalpha is highly expressed in the oviduct, while
      pigeon ERb is highly expressed in the ovary and kidney. We hypothesize that
      ERalpha mRNA predominates over that of ERbeta in the oviduct. The expression of
      ERalpha can be down-regulated by 17beta-estradiol, and the knockdown of ERalpha
      promoted OVA mRNA expression in cultured POECs, indicating that ERalpha may play
      an important role in OVA secretion. 

PMID- 24668682
TI  - Is there any association between childhood cardiac septal defects and ROCK2 gene
      polymorphism?
AB  - Rho/Rho-kinase pathway plays a critical role in the regulation of cellular
      functions such as proliferation and migration. One of the possible theories of
      the development of ventricular septal defects is cell migration disorder. The aim
      of this study was to analyze the genotype distributions and allele frequencies
      for the ROCK2 gene Thr431Asn polymorphisms in the development of cardiac septal
      defects in a Turkish population. In this case-control study, 300 patients with
      cardiac defects (150 patients with ventricular and 150 patients with atrial
      septal defects) and control group (150 healthy control subjects) were
      investigated. A single-nucleotide polymorphism in ROCK2 gene Thr431Asn was
      analyzed by real-time PCR using a Light-Cycler. Neither genotype distributions
      nor the allele frequencies for the Thr431Asn polymorphism showed a significant
      difference between the groups. These results suggest that there is no association
      of the ROCK2 gene Thr431Asn polymorphism with the development of cardiac septal
      defects in pediatric patients. 

PMID- 24668683
TI  - Outcomes of laryngectomy in elderly patients with laryngeal carcinoma.
AB  - Laryngeal carcinoma is a common tumor of the head and neck region. This study
      aimed to examine the outcomes of laryngectomy in elderly patients with laryngeal
      carcinoma. One-hundred twenty-two patients (male, 117; female, 5) aged 60 years
      or older (range, 60-94 years) who underwent laryngectomy between 1996 and 2010
      were included. All patients were diagnosed with squamous cell carcinoma of the
      larynx, and 95 patients (77.9%) had additional concurrent diseases. Tumors were
      staged according to the TNM categories of the American Joint Committee on Cancer
      2002 criteria; there were 16 stage-I, 24 stage-II, 52 stage-III, and 30 stage-IV
      cases. With regard to treatment modalities, 10 patients underwent transoral laser
      laryngectomy, 25 underwent partial laryngectomy, and 87 underwent total
      laryngectomy. When necessary, neck dissection was performed according to the
      Dalian criteria set in 2004 (a Chinese standard). Of the 122 cases, there were
      114 cases of grade I (93.4%), 5 cases of grade II, and 3 cases of grade III
      (pharyngeal fistula in 2 cases recovered after 2 weeks of care) wound healing. No
      significant differences were observed in the occurrence or severity of
      comorbidities. The 1-, 3-, and 5-year actuarial survival rates were 97.5%
      (119/122), 84.4% (92/109), and 68.4% (67/98), respectively. Age alone should not
      be used to determine treatment options for elderly patients with squamous cell
      carcinoma. Presuming that careful pre-treatment evaluations are performed,
      laryngectomy is a key method for elderly patients with laryngeal carcinoma. 

PMID- 24668684
TI  - Identification of a characteristic copy number alteration profile by high
      resolution single nucleotide polymorphism arrays associated with metastatic
      sporadic colorectal cancer.
AB  - BACKGROUND: Metastatic dissemination is the most frequent cause of death in
      patients with sporadic colorectal cancer (sCRC). It is believed that the
      metastatic process is related at least in part to a specific background of
      genetic alterations accumulated in cells from primary tumors, and the ability to
      detect such alterations is critical for the identification of patients with sCRC
      who are at risk of developing metastases. METHODS: The authors used high
      resolution, 500-K single nucleotide polymorphism arrays to identify copy number
      alteration profiles present at diagnosis in primary tumors from patients with
      metastatic (n = 23) versus nonmetastatic (n = 26) sCRC. RESULTS: The results
      revealed a characteristic pattern of copy number alterations in metastatic sCRC
      tumors that involved losses of 23 regions at chromosomes 1p, 17p, and 18q,
      together with gains of 35 regions at chromosomes 7 and 13q. CONCLUSIONS: In line
      with expectations, the copy number profile investigated involved multiple genes
      that were associated previously with sCRC (ie, SMAD2) and/or the metastatic
      process (ie, podocalyxin-like [PODXL]), and it also was associated with a poorer
      outcome.

PMID- 24668685
TI  - Energy balance, macronutrient intake, and hydration status during a 1,230 km
      ultra-endurance bike marathon.
AB  - Athletes competing in ultra-endurance events are advised to meet energy
      requirements, to supply appropriate amounts of carbohydrates (CHO), and to be
      adequately hydrated before and during exercise. In practice, these
      recommendations may not be followed because of satiety, gastrointestinal
      discomfort, and fatigue. The purpose of the study was to assess energy balance,
      macronutrient intake and hydration status before and during a 1,230-km bike
      marathon. A group of 14 well-trained participants (VO2max: 63.2 +/- 3.3
      ml/kg/min) completed the marathon after 42:47 hr. Ad libitum food and fluid
      intake were monitored throughout the event. Energy expenditure (EE) was derived
      from power output and urine and blood markers were collected before the start,
      after 310, 618, and 921 km, after the finish, and 12 hr after the finish. Energy
      intake (EI; 19,749 +/- 4,502 kcal) was lower than EE (25,303 +/- 2,436 kcal) in
      12 of 14 athletes. EI and CHO intake (average: 57.1 +/- 17.7 g/hr) decreased
      significantly after km 618 (p < .05). Participants ingested on average 392 +/- 85
      ml/hr of fluid, but fluid intake decreased after km 618 (p < .05). Hydration
      appeared suboptimal before the start (urine specific gravity: 1.022 +/- 0.010
      g/ml) but did not change significantly throughout the event. The results show
      that participants failed to maintain in energy balance and that CHO and fluid
      intake dropped below recommended values during the second half of the bike
      marathon. Individual strategies to overcome satiety and fatigue may be necessary
      to improve eating and drinking behavior during prolonged ultra-endurance
      exercise. 

PMID- 24668686
TI  - Selenium and selenoprotein function in brain disorders.
AB  - Selenoproteins are important for normal brain function, and decreased function of
      selenoproteins can lead to impaired cognitive function and neurological
      disorders. This review examines the possible roles of selenoproteins in
      Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD),
      and epilepsy. Selenium deficiency is associated with cognitive decline, and
      selenoproteins may be helpful in preventing neurodegeneration in AD. PD is
      associated with impaired function of glutathione peroxidase selenoenzymes. In HD,
      selenium deters lipid peroxidation by increasing specific glutathione
      peroxidases. Selenium deficiency increases risk of seizures in epilepsy, whereas
      supplementation may help to alleviate seizures. Further studies on the mechanisms
      of selenoprotein function will increase our understanding of how selenium and
      selenoproteins can be used in treatment and prevention of brain disorders.

PMID- 24668687
TI  - TiO(2) nanospheres: a facile size-tunable synthesis and effective light
      harvesting layer for dye-sensitized solar cells.
AB  - A facile route to synthesize amorphous TiO2 nanospheres by a controlled oxidation
      and hydrolysis process without any structure-directing agents or templates is
      presented. The size of the amorphous TiO2 nanospheres can be easily turned from
      20 to 1500 nm by adjusting either the Ti species or ethanol content in the
      reaction solution. The phase structure of nanospheres can be controlled by
      hydrothermal treatment. The TiO2 nanospheres show excellent size-dependent light
      scattering effects and can be structured into a light-harvesting layer for dye
      sensitized solar cells with a quite high power conversion efficiency of 9.25 %. 

PMID- 24668688
TI  - New biphasic solvent system based on cyclopentyl methyl ether for the
      purification of a non-polar synthetic peptide by pH-zone refining centrifugal
      partition chromatography.
AB  - A new type 1 ternary biphasic system composed of cyclopentyl methyl ether,
      dimethylformamide and water was developed, characterized and successfully used
      for the purification of a lipophilic, protected peptide by pH-zone refining
      centrifugal partition chromatography. The protected peptide is an 8-mer, key
      intermediate in bivalirudin (Angiomax(r)) synthesis and shows a very low
      solubility in the solvents usually used in liquid chromatography. All ionic
      groups, except the N-terminal end of the peptide, are protected by a benzyl
      group. The purification of this peptide was achieved with a purity of about
      99.04% and a recovery of 94% using the new ternary biphasic system cyclopentyl
      methyl ether/dimethylformamide/water (49:40:11, v/v) in the descending pH-zone
      refining mode with triethylamine (28 mM) as the retainer and methanesulfonic acid
      (18 mM) as the eluter. 

PMID- 24668689
TI  - Long-term exposure to dietary sources of genistein induces estrogen-independence
      in the human breast cancer (MCF-7) xenograft model.
AB  - SCOPE: The long-term effect of exposure to relevant dietary levels of genistein
      (GEN) on estrogen receptor-positive (ER+) human breast cancer (MCF-7) progression
      after GEN withdrawal in athymic mice xenograft model was studied. MATERIALS AND
      METHODS: Feeding studies were conducted to determine the estrogenic effect of
      diets on MCF-7 tumor growth: (1) implantation (19 weeks) and withdrawal (6 weeks)
      of 17beta-estradiol (E2 ); (2) dietary GEN 500 and 750 ppm during
      treatment/withdrawal for 23/10 and 15/9 weeks, respectively; and, (3) dietary soy
      protein isolate (SPI) containing GEN 180 ppm for 31/9 weeks of
      treatment/withdrawal. MCF-7 tumors grew fast in the presence of E2 implantation
      and abruptly regressed completely after E2 withdrawal. At different rates,
      dietary GEN alone (500 and 750 ppm) and GEN (180 ppm)-containing SPI stimulated
      MCF-7 tumor growth. After removal of the stimulus diet, tumors induced by 750 ppm
      GEN, but not 500 ppm GEN or SPI, regressed completely. The protein expression of
      epidermal growth factor receptor 2 (HER2) was higher in the GEN- and SPI-induced
      nonregressing (GINR) tumors compared to MCF-7 and E2 controls. CONCLUSION: Long
      term consumption of low GEN doses (<=500 ppm) promotes MCF-7 tumor growth and
      results in GINR tumors with more aggressive and advanced growth phenotypes.

PMID- 24668690
TI  - An amino acid code for beta-sheet packing structure.
AB  - To understand the relationship between protein sequence and structure, this work
      extends the knob-socket model in an investigation of beta-sheet packing. Over a
      comprehensive set of beta-sheet folds, the contacts between residues were used to
      identify packing cliques: sets of residues that all contact each other. These
      packing cliques were then classified based on size and contact order. From this
      analysis, the two types of four-residue packing cliques necessary to describe
      beta-sheet packing were characterized. Both occur between two adjacent hydrogen
      bonded beta-strands. First, defining the secondary structure packing within beta
      sheets, the combined socket or XY:HG pocket consists of four residues i, i+2 on
      one strand and j, j+2 on the other. Second, characterizing the tertiary packing
      between beta-sheets, the knob-socket XY:H+B consists of a three-residue XY:H
      socket (i, i+2 on one strand and j on the other) packed against a knob B residue
      (residue k distant in sequence). Depending on the packing depth of the knob B
      residue, two types of knob-sockets are found: side-chain and main-chain sockets.
      The amino acid composition of the pockets and knob-sockets reveal the sequence
      specificity of beta-sheet packing. For beta-sheet formation, the XY:HG pocket
      clearly shows sequence specificity of amino acids. For tertiary packing, the
      XY:H+B side-chain and main-chain sockets exhibit distinct amino acid preferences
      at each position. These relationships define an amino acid code for beta-sheet
      structure and provide an intuitive topological mapping of beta-sheet packing.

PMID- 24668691
TI  - Bioactive compound reveals a novel function for ribosomal protein S5 in hepatic
      stellate cell activation and hepatic fibrosis.
AB  - Liver fibrosis and its endstage, cirrhosis, represent a major public health
      problem worldwide. Activation of hepatic stellate cells (HSCs) is a central event
      in hepatic fibrosis. However, the proteins that control HSC activation are
      incompletely understood. Here we show that (6aS, 10S, 11aR, 11bR, 11cS)-10
      methylamino-dodecahydro-3a, 7a-diaza-benzo [de]anthracene-8-thione (MASM)
      exhibits potent inhibitory activity against liver fibrosis in vitro and in vivo
      associated with the reduction of Akt phosphorylation. Furthermore, ribosomal
      protein S5 (RPS5) was identified as a direct target of MASM, which stabilized
      RPS5 in cultured HSCs and in the liver of experimental animals after
      dimethylnitrosamine (DMN) or bile duct ligation (BDL). Functional studies
      revealed that RPS5 could prevent HSC activation. RPS5 overexpression in HSCs
      resulted in Akt dephosphorylation at both Ser473 and Thr308, and led to
      subsequent dephosphorylation of GSK3beta or P70S6K. Progression of DMN- and BDL
      induced hepatic fibrosis was aggravated by Rps5 knockdown and alleviated by RPS5
      overexpression, which correlated with the modulation of Akt phosphorylation and
      HSC number in the fibrotic livers. Moreover, RPS5 was substantially reduced in
      the transdifferentiated HSCs, experimental fibrotic livers, and human cirrhosis
      samples. CONCLUSION: These results demonstrate that RPS5 is implicated in hepatic
      fibrogenesis and may represent a promising target for potential therapeutic
      intervention in liver fibrotic diseases.

PMID- 24668692
TI  - Attention-network specific alterations of structural connectivity in the
      undamaged white matter in acute neglect.
AB  - Visual neglect results from dysfunction within the spatial attention network. The
      structural connectivity in undamaged brain tissue in neglect has barely been
      investigated until now. In the present study, we explored the microstructural
      white matter characteristics of the contralesional hemisphere in relation to
      neglect severity and recovery in acute stroke patients. We compared age-matched
      healthy subjects and three groups of acute stroke patients (9 +/- 0.5 days after
      stroke): (i) patients with nonrecovered neglect (n = 12); (ii) patients with
      rapid recovery from initial neglect (within the first week post-stroke, n = 7),
      (iii) stroke patients without neglect (n = 17). We analyzed the differences
      between groups in grey and white matter density and fractional anisotropy (FA)
      and used fiber tracking to identify the affected fibers. Patients with
      nonrecovered neglect differed from those with rapid recovery by FA-reduction in
      the left inferior parietal lobe. Fibers passing through this region connect the
      left-hemispheric analogues of the ventral attention system. Compared with healthy
      subjects, neglect patients with persisting neglect had FA-reduction in the left
      superior parietal lobe, optic radiation, and left corpus callosum/cingulum.
      Fibers passing through these regions connect centers of the left dorsal attention
      system. FA-reduction in the identified regions correlated with neglect severity.
      The study shows for the first time white matter changes within the spatial
      attention system remote from the lesion and correlating with the extent and
      persistence of neglect. The data support the concept of neglect as disintegration
      within the whole attention system and illustrate the dynamics of structural
      functional correlates in acute stroke.

PMID- 24668693
TI  - Catalytic asymmetric synthesis of [2,3]-fused indoline heterocycles through
      inverse-electron-demand aza-Diels-Alder reaction of indoles with azoalkenes.
AB  - An unprecedented catalytic asymmetric inverse-electron-demand aza-Diels-Alder
      reaction of indoles with in situ formed azoalkenes is reported. A diverse set of
      [2,3]-fused indoline heterocycles were achieved in generally good yields (up to
      97 %) with high regioselectivity and diastereoselectivity (>20:1 d.r.), and with
      excellent enantioselectivity (up to 99 % ee). 

PMID- 24668694
TI  - The host response to allogeneic and xenogeneic biological scaffold materials.
AB  - The clinical use of biological scaffold materials has become commonplace. Such
      scaffolds are composed of extracellular matrix (ECM), or components of ECM,
      derived from allogeneic or xenogeneic tissues. Such scaffold materials vary
      widely in their source tissue, processing methods and sterilization methods. The
      success or failure of an ECM scaffold for a given application is dependent on the
      host response following implantation; a response that is largely mediated by the
      innate immune system and which is influenced by a numerous factors, including the
      processing methods used in the preparation of biological scaffolds. The present
      paper reviews various aspects of the host response to biological scaffolds and
      factors that affect this response. In addition, some of the logistical,
      regulatory and reconstructive implications associated with the use of biological
      scaffolds are discussed.

PMID- 24668695
TI  - Advancing safe drug use through interprofessional learning (IPL): a pilot study.
AB  - Interprofessional collaborative patient-centered care (IPCPC) improves healthcare
      quality and cost. Drug-related morbidity drives healthcare costs, thus requiring
      IPCPC approaches. The lack of educational preparedness for would-be IPCPC
      practitioners underlies the failure of historic IPCPC attempts, hence today's
      emphasis on pre-licensure interprofessional education (IPE). A pilot IPE class
      was conducted on rational drug use (RDU) through rational drug prescribing.
      Twenty fourth-year nursing students and 88 second-year medical students
      participated (8-10 medical per 2-3 nursing students) in small group activity in a
      lecture hall. A case study on rational drug choice and prescription writing
      processes from medical and nursing perspectives was used. Eighty of 108 (74%)
      students completed the post-activity questionnaire and were satisfied with the
      class, with a mean weighted score (mws) of 0.8. The learning outcomes (mws = 1.0)
      contributed more (P < 0.05) to students satisfaction than the
      organization/delivery (mws = 0.6). A majority (84-94%) agreed the class
      objectives were achieved and favored more classes. Interaction with other
      healthcare professionals and the crowded classroom were, respectively, the most-
      and least-liked aspects of the class. The study revealed students' appetite for
      IPE, highlights the challenges in developing IPE curricula, and could serve as
      impetus for schools developing IPE for RDU curricula. 

PMID- 24668696
TI  - A cryptic familial rearrangement of 11p15.5, involving both imprinting centers,
      in a family with a history of short stature.
AB  - Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by
      intrauterine and postnatal growth retardation, dysmorphic facial features and
      body asymmetry. Both hypomethylation of the telomeric imprinting control region 1
      (ICR1) at 11p15.5 and maternal duplication of 11p15.5 have been implicated in the
      etiology of this disorder. Here we report the origin and segregation of the first
      reported between-arm intrachromosomal insertion of 11p15.5 that encompasses both
      ICR1 and ICR2 in a multigenerational family with a history of short stature. One
      (or any odd number) crossover within the centromeric segment during meiosis would
      produce recombinant chromosomes; one with a duplication of the inserted segment
      and the other a deletion. In this 4-generation family, there were six instances
      of transmission of the recombinant chromosome with duplication of the11p15.5
      segment, which leads to a SRS phenotype when maternally inherited and a Beckwith
      Wiedemann phenotype when paternally transmitted. The size of the duplicated
      region is ~1.9 Mb as determined by microarray analysis. This study provides
      further evidence that maternally inherited duplications of 11p15.5 result in a
      SRS phenotype that includes short stature and other variable features. The
      methylation status of the extra copy of the duplicated region of 11p15.5
      ultimately predicts the resulting phenotype. Thus, the different phenotype based
      on parental mode of transmission is of importance in the genetic counseling of
      these patients.

PMID- 24668697
TI  - Prostatectomy v radiotherapy: possible detrimental effect of hormonal
      manipulation in patients receiving radiotherapy.

PMID- 24668698
TI  - Weight, pregnancy and oral contraceptives affect intravenous paracetamol
      clearance in young women.
AB  - OBJECTIVES: Because of the extensive variability in paracetamol clearance in
      young women, published data were pooled with newly collected observations in
      search of covariates of paracetamol pharmacokinetics (PK) within this specific
      population. SUBJECTS AND METHODS: PK estimates and clinical characteristics
      [pregnant, weight, exposure to oral contraceptives (OC)] in young women following
      IV loading dose (2 g paracetamol) were pooled, using a non-compartmental linear
      disposition model in individual time-concentration profiles. Data were reported
      by median and range. Rank correlation was used to link clearance (l/h) to weight,
      Mann Whitney U test to compare clearance (l/h.m-2) between subgroups (pregnant,
      OC exposure). Finally, a multiple regression model with clearance (l/h) in all
      women and all non-pregnant women was performed. RESULTS: Based on 73 paracetamol
      PK estimates, a 8-fold variability in clearance (range 7.1-62.2 l/h) was
      documented, in part explained by a correlation (r2=0.36) between clearance (l/h)
      and weight. Clearance (l/h and l/h.m-2) and distribution volume (l) at delivery
      (n=36) were higher compared to non-pregnant observations. In non-pregnant women,
      women on OC (n=20) had a higher paracetamol clearance (l/h.m-2) compared to women
      (n=17) not on OC (p = 0.023). Weight (p = 0.0043) and pregnancy (p = 0.02) were
      independent variables (r=0.56) of paracetamol clearance (l/h). In non-pregnant
      women, weight (p = 0.009) and OC exposure (p = 0.03) were independent variables
      (r=0.51). CONCLUSIONS: Weight, pregnancy and OC result in higher clearance of IV
      paracetamol in young women. Besides compound specific relevance, these findings
      also unveil covariates of drug metabolism in young women.

PMID- 24668699
TI  - The potential ameliorative effects of melatonin against cyclophosphamide-induced
      DNA damage in murine bone marrow cells.
AB  - OBJECTIVES: The protection afforded by melatonin, a pineal secretory product,
      against cyclophosphamide (CP)-induced genotoxicity in murine bone marrow cells
      was tested using micronuclei as an index of induced chromosomal damage. MATERIALS
      AND METHODS: Mice were pretreated with four different doses of melatonin (2.5, 5,
      10 and 20 mg/kg by weight, b.w.) via intraperitoneal injection for five
      consecutive days followed by injection with CP (60 mg/kg b.w.) 1 hr after the
      last injection of melatonin on the fifth day. After 24 hr, mice were euthanized
      by cervical dislocation to evaluate micronucleated polychromatic erythrocytes
      (MnPCEs) and the ratio of polychromatic erythrocyte/polychromatic
      erythrocyte+normochromatic erythrocyte [PCE/(PCE+NCE)]. Histological examination
      of the bone marrow was also performed. RESULTS: Treatment with melatonin
      significantly reduced the number of MnPCEs induced by CP at all doses (p <
      0.0001). At 20 mg/kg, melatonin had a maximum chemoprotective effect and reduced
      the number of MnPCEs by 6.93 fold and completely normalized the PCE/ (PCE+NCE)
      ratio. Administration of 20 mg/kg of melatonin led to marked proliferation and
      hypercellularity of immature myeloid elements after mice were treated with CP, as
      well as mitigated bone marrow suppression induced by CP. CONCLUSIONS: Our study
      revealed that melatonin has a potent antigenotoxic effect against CP-induced
      toxicity in mice, which may be due to the scavenging of free radicals and
      increased antioxidant status. Because melatonin is a safe, natural compound, it
      could be used concomitantly as a supplement to protect people undergoing
      chemotherapy.

PMID- 24668700
TI  - Use of Flavonoids for the treatment of symptoms after hemorrhoidectomy with
      radiofrequency scalpel.
AB  - OBJECTIVES: Control of postoperative symptoms is of paramount importance in
      proctologic surgery. Phlebotropic activity, protective effect on the capillaries
      and anti-inflammatory properties of the flavonoids have been reported in several
      studies. They have been used to treat a variety of conditions including chronic
      venous insufficiency, lymphedema and hemorrhoids. Numerous trials, assessing the
      effect of phlebotonics in treating the symptoms and signs of haemorrhoidal
      disease, suggest that there is a potential benefit. Our trial was conducted to
      evaluate whether the flavonoids reduce postoperative bleeding, pain and other
      symptoms after hemorrhoidectomy. PATIENTS AND METHODS: We compared the results
      obtained in 24 patients undergoing open hemorrhoidectomy with radiofrequency
      scalpel. Our study cohort was randomized in two groups: the Group A received
      flavonoids in the postoperative period, the Group B has constituted the control
      group, without administration of study drug. Follow-up outpatient visits were
      performed on 7, 15 and 30 postoperative day (POD). During the visits the patients
      expressed trough a list of specific questions, based on a scoring system (1 to
      10), their opi-nion about the extent of postoperative symptoms as pain, bleeding,
      tenesmus, pruritus and perianal weight. RESULTS: We observed that the results
      obtained after 7 days of surgery are similar in both study groups. Even after 15
      and 30 days no significant changes were observed between the two groups about
      pain and bleeding. Instead, we observed significant differences regarding
      tenesmus (group A: 8.0+/-1.1 vs Group B: 5.4 +/- 1.5 at 15 POD, p < 0.05; group
      A: 9.1+/-0.8 vs Group B: 5.7 +/- 0.9 at 30 POD, p < 0.05), pruritus (group A: 7.1
      +/- 1.4 vs Group B: 4.8 +/- 1 at 15 POD, p < 0.05; group A: 9.5 +/- 0.5 vs Group
      B: 6.6 +/- 0.8 at 30 POD, p < 0.05) and perianal weight (group A: 7.2 +/- 0.9 vs
      Group B: 6.2 +/- 0.8 at 15 POD, p < 0.05; group A: 9.75 +/- 0.4 vs Group B: 7.3
      +/- 0.9 at 30 POD, p < 0.05). CONCLUSIONS: Our results confirm the usefulness of
      this drug to reduce the prevalence and the importance of post-hemorrhoidectomy
      symptoms and make more comfortable the postoperative period.

PMID- 24668701
TI  - Effect of hypothyroidism in the thyroidectomized rats on immunophenotypic
      characteristics and differentiation capacity of adipose tissue derived stem
      cells.
AB  - INTRODUCTION: Thyroid hormones influence multiple physiological functions, like
      growth, differentiation, protein synthesis and metabolic rate. The hypothyroid
      state is a complex hormonal dysfunction rather than a single hormonal defect. The
      relation between hypothyroidism after thyroidectomy and stem cells is not clear.
      AIM: This study was designed to investigate the effect of thyroidectomy on the
      proliferation, telomerase enzyme activities, immunophenotypic properties and
      differentiation potentials of adipose tissue-derived (AT-) stem cells (SCs).
      MATERIALS AND METHODS: AT-SCs after 60 and 120 days of thyroidectomized (Tx) rats
      were compared to normal rats by flow cytometry and immunocytochemistry analyses,
      and their telomerase activities were estimated. RESULTS: The telomerase activity
      was found to be positive for AT-SCs of Tx rats of both 60 and 120 days used in
      this study, but a decrease was noticed in the cells with the long-term exposure
      to hypothyroidism. This might indicate the decrease in the regenerative ability
      of the AT-SCs after 120 days of Tx compared to cells after 60 days of Tx. Both
      cell lines were induced to differentiate into adipogenic, osteogenic and
      neurogenic cell lineages, but osteogenic marker expression was not detected in
      the undifferentiated AT-SCs of the Tx rats. Osteogenic differentiation was also
      failed in stem cells derived from Tx rats, shown by Alizarin red S staining and
      alkaline phosphates enzyme assays. DISCUSSION: These results suggest that
      hypothyroidism affected SCs, altered stem cell characteristics, like telomerase
      activity and loss of in vitro bone formation, but not adipogenic or neurogenic
      differentiation ability. CONCLUSIONS: Hypothyroidism after Tx affects the
      osteogenic differentiation capacity of stem cells, which might be one of the
      factors of bone loss due to postnatal hypothyroidism.

PMID- 24668702
TI  - Comparison of effects of nebivolol, carvedilol and irbesartan on left ventricular
      hypertrophy associated with hypertension.
AB  - OBJECTIVES: The aim of this study was to investigate if the new generation beta
      blockers are as effective as irbesartan, which is an angiotensin receptor blocker
      (ARB), on left ventricular hypertrophy (LVH). PATIENTS AND METHODS: The study
      included 85 patients (average age: 56.6+/-9.6 year) with stage 1 and 2
      hypertension, who previously didn't receive an antihypertensive treatment, but
      diagnosed with LVH echocardiographically. The patients were divided into three
      different treatment groups: irbesartan (n=28), nebivolol (n=25) and carvedilol
      (n=32). The patients were reassessed clinically and echocardiographically at 3, 6
      and 12 months after the treatments. RESULTS: There was no statistically
      significant difference in baseline left ventricular mass index (LVMI) and other
      parameters among the three treatment groups (p > 0.05). Although there was no
      significant decrease in LVMI in irbesartan and carvedilol groups at 3 months
      after the treatment (p > 0.05), the values measured at 6 and 12 months (p <
      0.0001) were significant. The decrease in LVMI in the nebivolol group was
      significant at 3, 6 and 12 months (p < 0.0001). There was a significant
      difference in measurements at 12 months (p < 0.05). CONCLUSIONS: Both of the new
      generation beta-blockers were more effective than irbesartan in the regression of
      LVH. A significant regression in LVH was observed 3 months after nebivolol
      treatment and 6 months after irbesartan and carvedilol treatments.

PMID- 24668703
TI  - Safety and tolerability evaluation of oral bosentan in adult congenital heart
      disease associated pulmonary arterial hypertension: a systematic review and meta
      analysis.
AB  - OBJECTIVES: In this study, we performed a systematic review and meta-analysis of
      oral bosentan in adult congenital heart disease associated pulmonary arterial
      hypertension (CHD-PAH) to evaluate its safety and tolerability. MATERIALS AND
      METHODS: Online electronic database including PubMed, EMBASE and Springer were
      searched from October 2006 to October 2013 to collect the clinical studies or
      cohort trials on CHD-PAH with bosentan treatment. Weight Mean Difference (WMD)
      and Standard Mean Difference (SMD) were used to evaluate the treatment safety and
      tolerability. Review Manager (RevMan) version 5.0 was performed for the data
      analysis. RESULTS: Totally 8 studies including 215 patients with CHD-PAH were
      enrolled in this research. With a period of 3-6 months oral bosentan treatment in
      patients, there were no significant differences in the scores of resting oxygen
      saturation (Resting SpO2), post-6-MWT SpO2 after 6-minutes' walktest (6-MWT) and
      Borg dyspnea index score (BDIs) compared with the baseline; the walking distance
      on 6-MWT increased significantly. With a period of one year or more oral bosentan
      treatment, the scores of resting SpO2 and post-6-MWT SpO2 increased
      significantly; there was no significant difference in BDIs and walking distance
      on 6-MWT. CONCLUSIONS: The short-term treatment with oral bosentan could increase
      walking distance on 6-MWT, and long-term treatment could increase the Resting
      SpO2 in CHD-PAH patients. Oral bosentan in CHD-PAH patients was safe and well
      tolerated.

PMID- 24668704
TI  - Importance of large conductance calcium-activated potassium channels (BKCa) in
      interleukin-1b-induced adhesion of monocytes to endothelial cells.
AB  - OBJECTIVE: The present study investigated the role of the large conductance
      calcium-activated potassium channels (BKCa) in interleukin-1b (IL-1b) induced
      inflammation. MATERIALS AND METHODS: Human umbilical vein endothelial cells
      (HUVECs) were isolated and cultured. Endothelial cell membrane potential
      measurements were accomplished using the fluorescent dye DiBAC4(3). The role of
      BKCa was assessed using iberiotoxin, a highly selective BKCa inhibitor. Changes
      in the calcium intracellular calcium were investigated using Fura-2-AM imaging.
      Fluorescent dyes DCF-AM and DAF-AM were further used in order to measure the
      formation of reactive oxygen species (ROS) and nitric oxide (NO) synthesis,
      respectively. Endothelial cell adhesion tests were conducted with BCECF-AM
      adhesion assay and tritium thymidine uptake using human monocytic cells (U937).
      Expression of cellular adhesion molecules (ICAM-1, VCAM-1) was determined by flow
      cytometer. RESULTS: Interleukin-1b induced a BKCa dependent hyperpolarization of
      HUVECs. This was followed by an increase in the intracellular calcium
      concentration. Furthermore, IL-1b significantly increased the synthesis of NO and
      ROS. The increase of intracellular calcium, radicals and NO resulted in a BKCa
      dependent adhesion of monocytes to HUVECs. Endothelial cells treated with IL-1b
      expressed both ICAM-1 and VCAM-1 in significantly higher amounts as when compared
      to controls. It was further shown that the cellular adhesion molecules ICAM-1 and
      VCAM-1 were responsible for the BKCa-dependent increase in cellular adhesion.
      Additionally, inhibition of the NADPH oxidase with DPI led to a significant
      downregulation of IL-1b-induced expression of ICAM and VCAM, as well as
      inhibition of eNOS by L-NMMA, and intracellular calcium by BAPTA. CONCLUSIONS:
      Activation of the endothelial BKCa plays an important role in the IL-1b-induced
      monocyte adhesion to endothelial cells.

PMID- 24668705
TI  - The prevalence of Familial Mediterranean Fever common gene mutations in patients
      with simple febrile seizures.
AB  - BACKGROUND: Febrile seizures (FS) represent the most common form of childhood
      seizures that occurs in 2-5 % of the children younger than 6 years. There have
      been many recent reports on the molecular genetic and pathogenesis of FC. It has
      been recognized that there is significant genetic component for susceptibility of
      FC with different reported mutation. FEB1, FEB2, FEB4, SCNA1, SCNA2, GABRG2 and
      IL-1beta are related to with febrile convulsions (FCs). Interleukin 1beta (IL
      1beta) is a cytokine that contributes to febrile inflammatory responses. There
      are conflicting results on increasing this cytokine in serum during FC. AIM: The
      determine the association between mutations of MEFV gene product pyrine and
      febrile seizures. PATIENTS AND METHODS: The study was carried out on 104 children
      that were diagnosed as FS and 96 healthy children. MEFV gene mutations were
      detected and analyzed with PyroMark Q24. PCR was performed using the PyroMark PCR
      Kit and pyrosequencing reaction was conducted on instrument instructions.
      RESULTS: M694V is the most common mutation in our patient group and we found a
      significant association between MEFV gene mutations and FSs. Of 104 patients, 68
      were heterozygotes for any mutation and 10 patients were compound. 17.7% of
      control group were heterozygotes for any studied mutation.Statistical analyses
      showed that there was strongly significant statistical difference between results
      obtained from FS and control group (X = 46.20, p < 0.0001). CONCLUSIONS: MEFV
      gene mutations, especially M694V mutation, are positively associated with FSs.

PMID- 24668706
TI  - Candidemia in intensive care unit: a nationwide prospective observational survey
      (GISIA-3 study) and review of the European literature from 2000 through 2013.
AB  - BACKGROUND: Candida bloodstream infections (BSI) represent an important problem
      in Intensive Care Units (ICUs). The epidemiology of candidemia is changing with
      an increase in the proportion of Candida (C.) non-albicans. OBJECTIVES: An
      Italian 2-year observational survey on ICU was conducted to evaluate the species
      distribution and possible differences between BSI caused by C. albicans and C.
      non-albicans. For comparative purposes, we performed a European literature-based
      review to evaluate distribution and frequency of Candida spp. causing ICU
      candidemia, during the period 2000-2013. MATERIALS AND METHODS: This laboratory
      based survey involved 15 microbiology centers (GISIA-3 study). All candidemia
      episodes in adult patients were considered. Data were prospectively collected
      from 2007 to 2008. PubMed was searched for peer-reviewed articles. RESULTS: In
      total, 462 candidemia episodes were collected. C. albicans accounted for 49.4% of
      the isolates, followed by C. parapsilosis (26.2%) and C. glabrata (10.4%).
      Mortality was higher in patients with C. non-albicans than C. albicans (47.3% vs.
      32.4 %, p > 0.05). Among risk factors, parenteral nutrition was more common (p =
      0.02) in non-albicans candidemia, while surgery was more frequent (p = 0.02) in
      C. albicans candidemia. Twenty-four relevant articles were identified. C.
      albicans was the predominant species in almost all studies (range 37.9% -76.3%).
      C. glabrata was commonly isolated in the German-speaking countries, France, UK
      and North Europe; C. parapsilosis in Turkey, Greece and Spain. CONCLUSIONS:
      Although C. non-albicans BSI is increasing, our study shows that C. albicans is
      still the predominant species in ICU candidemia. There are differences in the
      epidemiology of Candida BSI among European countries, with a prevalence of C.
      glabrata and C. parapsilosis in Northern and Southern countries, respectively.

PMID- 24668707
TI  - Evaluation of complement system in children with Crimean-Congo hemorrhagic fever.
AB  - OBJECTIVES: The complement system participates in the defense of the body against
      viral infections through various mechanisms. In the present study conducted on
      children having Crimean-Congo Hemorrhagic Fever (CCHF), the aim was to evaluate
      whether the complement system had a role in the pathogenesis of the disease.
      PATIENTS AND METHODS: Forty-one patients diagnosed with CCHF and 32 healthy
      controls were included in the study. Serum complement component 3 (C3), 4 (C4)
      and complement product Bb (Bb) levels were measured in both groups. RESULTS:
      Compared to the control group, serum C3 levels were lower and Bb levels were
      higher in CCHF patients (p < 0.01). Moreover, in the patient group, C3 levels
      were positively correlated with WBC and PLT counts, and Bb levels were positively
      correlated with AST, ALT and LDH activities. In the patient group, serum Bb
      levels were negatively correlated with WBC and PLT counts. CONCLUSIONS: The
      results of the present study suggest that increased activity of the alternative
      pathway of the complement system in children with CCHF may have a role in the
      pathogenesis of the disease.

PMID- 24668708
TI  - Effects of energy controllable steep pulses on intracellular calcium
      concentration and cell membrane potential.
AB  - BACKGROUND AND OBJECTIVES: Our previous experiments showed that steep pulses
      could kill tumor cells, but the mechanism is unclear yet. This study was to probe
      the effects of different dosages of energy controllable steep pulses on
      intracellular concentration of dissociative calcium ion ([Ca2+]i) and cell
      membrane potential. MATERIALS AND METHODS: The mammary carcinoma cells MDA-MB-231
      were divided into control group and 5 different dosages of Energy Controllable
      Steep Pulses (ECSP) treatment groups. The calcium ion in each group was labeled
      by Fluo-3/AM individually and the cell membrane potential was labeled by DiBAC4
      (3). The mean fluorescence intensity of fluorescent probe in mammary carcinoma
      cells was observed in quiet state by laser confocal microscopy after ECSP
      treatment The changes of calcium concentration and cell membrane potential in
      cells after ECSP treatment were analyzed. The changes of intracellular [Ca2+]i
      after ECSP treatment were also observed with and without calcium ion outside of
      the cells. RESULTS: The calcium ion outside of cells influx with lower dosage of
      pulse in quiet state. With the dosage increase, the intracellular calcium ion
      outflow. In real time kinetic detection, the mean fluorescence intensity of
      intracellular calcium ion was increased with the pulse electric field intensity
      raised in the lower ECSP. When the voltage was 285V, frequency was 100Hz, the
      [Ca2+]i decreased. The increase of intracellular calcium ion concentration was
      decreased without calcium ion than with calcium ion outside of cells, but still
      raised gradually. The lower dosage of ECSP could induce the fluorescence
      intensity of DiBAC4 (3) in cells increase, which showed that the lower dosage of
      ECSP could induce the depolarization of cells. With the dosage raised, the
      fluorescence intensity of DiBAC4 (3) in cells attenuated. This dosage of ECSP
      could induce the superpolarization of cell membrane. CONCLUSIONS: The lower
      dosage of ECSP can induce the depolarization of cell membrane and induce the
      inter flow of calcium ion outside of cell membrane. The higher dosage of ECSP can
      directly destroy the cell membrane and induce the superpolarization of cell
      membrane, then induce the outflow of intracellular calcium ion which causes the
      necrosis of tumor cells.

PMID- 24668709
TI  - Feasibility of intraperitoneal Trastuzumab treatment in a patient with peritoneal
      carcinomatosis from gastric cancer.
AB  - OBJECTIVES: This case report evaluates the feasibility and efficacy of
      intraperitoneal (IP) trastuzumab administration in gastric cancer (GC) patients
      with peritoneal carcinomatoses. METHODS: Peritoneal metastasis is a common sign
      of advanced tumor stage, tumor progression or disease recurrence in patients with
      GC. Recently, the role of HER2 overexpression in GC, occurring in about 20% of
      cases, is correlated with a worse prognosis. We report the case of 61-years old
      female, admitted to our Hospital after curative surgery for GC with over
      expression of HER2. Seven months after the start of first line chemotherapy
      treatment a pleuro-peritoneal disease progression occurred, documented by
      cytological exam; according to HER2 status, we decided to treat the patient with
      IP trastuzumab administration. RESULTS: Between September and October 2012, the
      patient (ECOG performance status was 0), underwent to 6 cycles of IP trastuzumab.
      Trastuzumab was administered weekly at a dose of 150 mg for each cycle after
      paracentesis. The safety was good, no local complications (e.g. abdominal pain,
      peritonitis) occurred. The clinical revaluation evidenced a stable peritoneal
      disease. CONCLUSIONS: To our knowledge this is the first report on Trastuzumab
      use to treat IP metastases from GC, with acceptable toxicity and local disease
      control.

PMID- 24668710
TI  - Quality of life in ulcerative colitis patients treated medically versus patients
      undergoing surgery.
AB  - OBJECTIVES: Approximately one third of patients with ulcerative colitis (UC)
      require surgery. AIM: Aim of this study was to assess the quality of life (QoL)
      of UC patients who have undergone surgery with ileorectal anastomosis (IRA) or
      ileal pouch-anal anastomosis (IPAA) compared to UC patients not operated.
      PATIENTS AND METHODS: Fifty consecutive UC patients for each group observed
      between 1988-2010 were included. To all patients was administered a self
      completed questionnaire with four different scores: intestinal symptoms (IS),
      systemic symptoms (SS), emotional function (EF), social function (SF) and an
      overall QoL score. RESULTS: Overall QoL score and three dimensions (SS, EF, SF)
      resulted not significantly different in the three groups, except for IS that
      resulted worst in the IRA-Group. According to the activity of disease it appeared
      that UC and IRA patients with mild activity had an overall QoL score similar to
      patients with complicated IPAA. A higher statistically different score of overall
      QoL was observed in patients with UC and IRA with moderate/severe disease.
      CONCLUSIONS: Results of the study demonstrate that overall QoL score is poorer in
      patients with UC and IRA with mild activity and in patients with complicated IPAA
      and is worst in patients with UC and IRA with moderate/severe activity.

PMID- 24668711
TI  - Predominance of rotavirus G8 genotype in hospitalized children with acute
      gastroenteritis in Yasuj, Iran.
AB  - BACKGROUND: Rotavirus infection is the most common cause of gastroenteritis among
      children worldwide. In this study, we were evaluated the occurrence of rotavirus
      infection and genotypes causing gastroenteritis among children under 5 years in
      Yasuj, Iran. MATERIALS AND METHODS: This cross sectional-descriptive study was
      done on 184 fecal samples collected from children aged < 5 years old with acute
      gastroenteritis. All the stool specimens were tested for group A rotavirus with
      enzyme immunoassays (EIA). Rotavirus-positive specimens were genotyped by the
      Nested reverse transcription polymerase chain reaction (RT-PCR) with using
      different type of specific primers. RESULTS: The prevalence of rotavirus was
      28.26% and predominant genotypes were G1 (1.92%), G2 (7.69%), G4 (1.92%), G8
      (46.16%), N.T.A (40.39%), mixed infections (1.92%). Predominance of rotavirus G8
      genotype in the current survey was reported for the first time in Iran. The
      highest prevalence of rotavirus infection was observed in autumn (48.08%), and
      the lowest in spring (5.77%). CONCLUSIONS: The result of study showed that
      prevalence of rotavirus genotypes in this region of the country is different from
      that of other regions. The continuous stability of rotavirus in Iran, regarding
      to the regional differentiates and prevalence of circulating strains, can be
      useful indication in order to supply and effective vaccine against the rotavirus
      infections.

PMID- 24668712
TI  - Impact of changes in postnatal nutrition on puberty onset and the expression of
      hypothalamic GnRH and ghrelin.
AB  - OBJECTIVES: Ghrelin is an octanoylated peptide hormone with multiple and diverse
      physiologic functions including an important role in energy homeostasis and
      reproduction. In this study, the adjustment effects of different postnatal
      nutritional status on puberty onset and the expression of hypothalamic ghrelin
      and gonadotrophin-releasing hormone (GnRH) were examined in 1 day-old female
      Sprague-Dawley rats. MATERIALS AND METHODS: Animals were randomly assigned into
      four groups: overnutrition group (Group O), normal group (Group N, control
      group), and undernutrition groups (Group U and U2). Western blot analysis and
      immunohistochemistry were used to analyze the expression of hypothalamic ghrelin
      and GnRH. RESULTS: With a low level expression of hypothalamic ghrelin, the
      appearance of puberty onset and secretion peak of GnRH in Group O was earlier
      than the other groups. CONCLUSIONS: Undernutrition delayed puberty onset and the
      GnRH peak, at the same time, promoted the expression of hypothalamic
      ghrelin.While, the expression of hypothalamic ghrelin was suppressed at puberty
      onset.

PMID- 24668713
TI  - Differential associations of circulating peroxiredoxins levels with indicators of
      glycemic control in type 2 diabetes mellitus.
AB  - OBJECTIVES: Oxidative stress is an important patho-physiological mechanism in the
      development and complications of type 2 diabetes mellitus. To counteract
      oxidative stress the peroxiredoxin enzyme system exists in body cells. Whether
      diabetic state and/or glycemic control affects circulating levels of
      peroxiredoxins (PRDXs) needs to be elucidated. This study planned to assess PRDXs
      plasma levels of isoforms 1, 2, 4 and 6 in type 2 diabetes and their potential
      associations with glycemic control and insulin resistance. PATIENTS AND METHODS:
      Plasma/serum samples were obtained from type 2 diabetic patients (n=53, 28F/25M)
      and control non-diabetic subjects (n=25, 7F/18M). According to HbA1c diabetics
      were divided into well-controlled (HbA1c < 7, n=19) and poorly-controlled (HbA1c
      > 7, n=34). PRDXs isoforms and insulin were measured using ELISA. RESULTS:
      Compared to those of the control subjects, plasma levels of PRDXs1, 2, 4 and 6
      were higher in diabetics. Poorly-controlled had lower levels of PRDXs2, 4 and 6
      compared to well-controlled patients. PRDXs2 and 6 plasma levels negatively
      correlated with fasting blood sugar and HbA1c. No associations were detected with
      other isoforms and glycemic status or other parameters. CONCLUSIONS: The high
      levels of PRDXs in diabetes may suggest their chaperone function and their
      differential association with indicators of glycemic control may suggest their
      biomarker role and different mechanisms of action that warrants further
      investigations.

PMID- 24668715
TI  - Umbilical CORD S100B levels in active and passive smoker women.
AB  - OBJECTIVES: In utero fetal exposure to tobacco smoke has been found to be
      associated with adverse pregnancy outcome and increased maternal and fetal risks.
      The aim of this study was to compare umbilical cord blood S100B levels of infants
      of active smoker, passive smoker and non-smoker mothers. SUBJECTS AND METHODS: A
      total of 82 women, 26 habitual smokers, 27 passive smokers and 29 controls, who
      were admitted for repeat elective cesarean delivery with uncomplicated term
      gestations were included in the study. The age, gravidity, parity and gestational
      week at delivery were recorded on admission for the delivery. Ultrasonographic
      evaluation was routinely done on admission and birth weights of the newborns were
      measured immediately upon delivery. Umbilical cord blood was collected following
      delivery of the infants and serum S100B levels were analyzed at the end of the
      study period. The groups were compared according to S100B levels. RESULTS: No
      significant difference was found between the three groups regarding age,
      gravidity, gestational week at delivery or birth weight of the infants (p >
      0.05). Biparietal diameter of the fetuses of active smoker mothers were
      significantly smaller than passive smokers and controls (90.3 +/- 1.8 vs 94.2 +/-
      2.8 and 93.8 +/- 2.5, respectively). Mean S100B level in the umbilical cord blood
      of active smokers was lower than passive smokers and controls (768.9 +/- 446.9 vs
      1050.1 +/- 383.2 and 1035.3 +/- 405.2) (p = 0.024). CONCLUSIONS: Fetuses of
      active smoker mothers had lower cord blood S100B levels, suggesting a possible
      injury of glial cells.

PMID- 24668714
TI  - Dexamethasone added to levobupivacaine in ultrasound-guided tranversus abdominis
      plain block increased the duration of postoperative analgesia after caesarean
      section: a randomized, double blind, controlled trial.
AB  - OBJECTIVES: When added to local anaesthetics, dexamethasone can prolong the
      duration of peripheral blocks. Dexamethasone has a long and efficient
      glucocorticoid structure and presents anti-inflammatory properties. The aim of
      this study was to determine the effect of dexamethasone on the block duration
      added to levobupivacaine used for transversus abdominis block (TAP) applied to
      patients who underwent caesarean section. PATIENTS AND METHODS: Forty-two
      patients with spinal anaesthesia in an American Society of Anesthesiologists
      (ASA) I-II risk group were included in the study and divided into two groups.
      Bilateral 30 ml 0.25% levobupivacaine and 2 ml 0.9% NaCl for the levobupivacaine
      group and bilateral 30 ml 0.25% levobupivacaine and 2 ml dexamethasone (8 mg) for
      the dexamethasone group were administered in a TAP block performed with
      ultrasonography. The time need for the first analgesic in the postoperative
      period was recorded. The numeric evaluation scale, and the total additional
      analgesic amounts were recorded. RESULTS: The time before the administration of
      the first additional analgesic dose was prolonged significantly in the
      dexamethasone group compared to the levobupivacaine group (p = 0.004). The pain
      scores were lower in the dexamethasone group for superficial pain. A significant
      difference for the dexamethasone group was observed in the evaluation of deep
      pain. The total consumption of tramadol was significantly lower in the
      dexamethasone group (p = 0.001). CONCLUSIONS: The utilization of dexamethasone,
      which has a prolonging effect on the transversus abdominis plane block, may be an
      alternative to epidural opioid analgesia in caesarean section. We observed that
      dexamethasone added to levobupivacaine in a TAP block applied for analgesia
      following a caesarean section procedure prolonged the time required for
      analgesia.

PMID- 24668716
TI  - Spontaneous regression of low-grade cervical intraepithelial lesions is
      positively improved by topical bovine colostrum preparations (GINEDIE(r)). A
      multicentre, observational, italian pilot study.
AB  - OBJECTIVES: Human papillomavirus (HPV) is the causal agent of cervical cancer.
      The great majority of abnormal Pap test results - almost 90% - is referrable to
      either atypical squamous intraepithelial lesion or CIN1. For these lesions,
      worldwide agreement exists concerning the high rate - ranging from 40% to 70% -
      of spontaneous regression over a period of 1-5 years. Host's immune response is a
      key point influencing the natural history of these conditions. Bovine colostrum
      is a natural agent positively promoting several immune activities against
      bacterial and viral agents. The aim of this report was to evaluate the potential
      positive effect of bovine colostrum-containing vaginal tablets administered to
      CIN1 diagnosed patients in a prospective trial in regards to spontaneous
      regression rate. PATIENTS AND METHODS: A series of 256 consecutive patients with
      histologically proven CIN1 recruited in a multicentre, observational, Italian
      study. Patients have been enrolled in a 24-weeks protocol of treatment and re
      tested at the end of the study. Rates of regression have been recorded. RESULTS:
      Overall regression rate to a negative histology at the end of the 6 month follow
      up was 75.5%. CONCLUSIONS: Regression to normal histology was observed in a very
      high rate of cases in a very short period compared to the natural history of
      these lesions. CIN1 patients could benefit from bovine colostrum topical
      administration in terms of significantly shortening the regression time.

PMID- 24668717
TI  - Screening of differentially expressed genes related to severe sepsis induced by
      multiple trauma with DNA microarray.
AB  - OBJECTIVES: Severe sepsis after trauma still associated with a high mortality
      rate in intensive care units (ICU). In this study we aimed to identify genes
      related to multiple trauma complicated by severe sepsis. MATERIALS AND METHODS:
      The gene expression profile dataset GSE12624 including 36 samples of traumatic
      patients not complicated by sepsis and 34 traumatic patients complicated by
      sepsis was downloaded from GEO (Gene Expression Omnibus) database. The limma
      package in R was applied to identify differentially expressed genes (DEGs)
      between these two groups of samples. All the DEGs were divided into up- and down
      regulation groups according to the changes of their expression value, which were
      then subjected to GO enrichment analysis. Two genes with largest changes among
      the up- and down-regulation groups were selected. Interaction networks based on
      these two genes were constructed using HitPredict software and then pathway
      enrichment analysis for the networks were performed by WebGestalt software.
      RESULTS: A total of 21 up-regulated genes and 37 down-regulated genes were
      obtained, which were mainly related to GO terms "endopeptidase inhibitor
      activity" and "response to wounding", respectively. The |logFC| of genes PLAU
      (urokinase-type plasminogen activator) and MMP8 (matrix metalloproteinase-8)
      ranked first in down-regulated or up-regulated list. There were 18 genes which
      can interact with PLAU at a high degree of confidence while there were 5 genes
      with MMP8. Further analysis showed that PLAU was closely associated with the
      pathway "complement and coagulation cascades". CONCLUSIONS: PLAU and MMP8 may act
      as potential targets for diagnosis and therapy of trauma complicated by sepsis.

PMID- 24668718
TI  - Characterization of an injectable chitosan-demineralized bone matrix hybrid for
      healing critical-size long-bone defects in a rabbit model.
AB  - BACKGROUND: The effect of injectable demineralized bone matrix (DBM) on bone
      repair is not known. Here, we tested the hypothesis that injectable DBM can heal
      a critical-size diaphyseal radius defect in a rabbit model. MATERIALS AND
      METHODS: The bone defect was filled with DBM powder, injectable DBM or powdered,
      freeze-dried powdered allografts. Radiological determination, gross evaluation,
      histology, and micro-computer tomography was carried out 4, 8, and 12 weeks after
      the surgery, respectively. RESULTS: The injectable DBM group yielded better when
      compared with the freeze-dried powder group (p < 0.05). Moreover, biomechanical
      functionality was restored comparable to normal levels in the injectable DBM
      group. CONCLUSIONS: The injectable DBM was as effective in structurally and
      functionally repairing bone defects as the DBM powder and more effective than the
      freeze-dried bone powder. Thus, our study supports the use of injectable DBM for
      bone healing.

PMID- 24668719
TI  - Should fat graft be recommended in tendon scar treatment? Considerations on three
      cases (two feet and a severe burned hand).
AB  - OBJECTIVES: Lipostructure has been reported as a successful ancillary tool for
      surgery in tenolysis procedures, but to date no reports of its capability to
      resolve tendon adherence without further surgery have been reported. The aim of
      this study is to highlight the role of lipografting in the treatment of tendon
      and joint adherences. PATIENTS AND METHODS: In our experience, we started
      treating important tendon adherences together with nerve entrapment on the dorsal
      aspect of the foot in two cases and in a severe burned hand. RESULTS: We achieved
      good results both in terms of function and sensory recovery. A twenty four month
      follow up showed good maintenance of the ROM. We also reported gaining of almost
      30-40 degrees of a flexion contracure in the second finger of a burned hand,
      minimizing further surgery for scar contracture and tenoarthrolysis, with a
      stable follow up. CONCLUSIONS: We suggest that prior to refer to surgery scars
      involving tendons as well as joints should be considered for lipografting.

PMID- 24668720
TI  - Determining the combined effects of smoking and obesity on insulin resistance and
      inflammation.

PMID- 24668721
TI  - The Effect of Lifestyle Intervention on Body Composition, Glycemic Control, and
      Cardiorespiratory Fitness in Polycystic Ovarian Syndrome: A Systematic Review and
      Meta-Analysis.
AB  - INTRODUCTION: Polycystic ovarian syndrome (PCOS) affects 18-22% women of
      reproductive age. We conducted a systematic review and meta-analysis to quantify
      expected benefits of lifestyle (exercise and dietary) interventions on various
      clinical outcomes in PCOS. METHODS: Potential studies were identified by
      conducting systematic search of PubMed, the Cumulative Index to Nursing and
      Allied Health Literature, and Cochrane controlled trials registry (1966 to April
      2013) using key concepts of PCOS, exercise, dietary and lifestyle interventions.
      RESULTS: Significant improvements were seen in women who received lifestyle
      intervention vs. usual care, in body composition parameters of body mass index,
      mean difference (MD) = -0.12 kg.m(-2) (95% CI [-0.22, -0.03], p = .009), body
      mass MD = -3.42 kg (95% CI [-4.86, -1.99], p < .00001), waist circumference MD = 
      1.64 cm (95% CI [-2.09, -1.19], p < .00001), waist-hip ratio MD = -0.03 (95% CI [
      0.05, -0.01], p = .0002), and body fat % MD = -1.71% (95% CI [-3.10, -0.32], p =
      .02). Insulin did not improve, MD = -1.21 pmol/L (95% CI [-3.06, -0.63], p =
      .20). Lipid profile did not improve, total cholesterol MD = -0.02 mmol/L (95% CI
      [-0.25, 0.21], p = .89). C-reactive protein was significantly lower, MD = -0.47
      mmol/L (95% CI [-0.80, -0.15], p = .004). Significant improvements were also
      observed in cardiorespiratory fitness with exercise alone reducing resting heart
      rate, MD = -1.89 beats.min(-1) (95% CI [-2.90, -0.88], p = .0002), and peak VO2,
      MD = 4.86 ml.kg(-1).min(-1) (95% CI [2.83, 6.88], p < .00001). Lifestyle therapy
      also improved, peak VO2 MD = 5.09 ml.kg(-1).min(-1) (95% CI [3.13, 7.05], p <
      .00001). CONCLUSIONS: Our analyses suggest lifestyle intervention is optimal for
      improving body composition and cardiorespiratory fitness in women with PCOS.

PMID- 24668722
TI  - Women are more susceptible than men to oxidative stress and chromosome damage
      caused by polycyclic aromatic hydrocarbons exposure.
AB  - Exposure to environmental polycyclic aromatic hydrocarbons (PAHs) has been
      associated with increased risk of cancer, but evidence for gender differences in
      this association is limited. The aim of this study was to examine the gender
      differences in PAHs caused early genotoxic effects such as oxidative stress and
      chromosome damage, which are potential carcinogenic etiology of PAHs. A total of
      478 nonsmoking workers (272 men and 206 women) from a coke oven plant were
      recruited. We determined 16 environmental PAHs in their workplaces, and measured
      concentrations of 12 urinary PAH metabolites (OH-PAHs), plasma benzo[a]pyrene-r
      7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, urinary 8
      hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha),
      and micronucleus frequencies in lymphocytes in all subjects. It showed that,
      women working at the office, adjacent to the coke oven, and on the bottom or side
      of the coke oven displayed significantly higher levels of urinary 8-OHdG and 8
      iso-PGF2alpha, and lymphocytic micronucleus frequencies compared with men working
      at above areas, respectively (all P < 0.05). These gender differences remain
      significant after adjusted for potential confounders and urinary SigmaOH-PAHs or
      plasma BPDE-Alb adducts. A significant interaction existed between gender and
      BPDE-Alb adducts on increasing micronucleus frequencies (Pinteraction  < 0.001).
      We further stratified all workers by the tertiles of urinary SigmaOH-PAHs or
      plasma BPDE-Alb adducts, and the above gender differences were more evident in
      the median- and high-exposure groups (all P < 0.05). In conclusion, women were
      more susceptible than men to oxidative stress and chromosome damage induced by
      PAHs, which may add potential evidence underlying gender differences in PAH
      exposure-related lung cacinogenesis.

PMID- 24668723
TI  - High-performance liquid chromatography with diode-array detection cotinine method
      adapted for the assessment of tobacco smoke exposure.
AB  - Smoking is considered to be one of the main risk factors for cancer and other
      diseases and is the second leading cause of death worldwide. As the anti-tobacco
      legislation implemented in Europe has reduced secondhand smoke exposure levels,
      analytical methods must be adapted to these new levels. Recent research has
      demonstrated that cotinine is the best overall discriminator when biomarkers are
      used to determine whether a person has ongoing exposure to tobacco smoke. This
      work proposes a sensitive, simple and low-cost method based on solid-phase
      extraction and liquid chromatography with diode array detection for the
      assessment of tobacco smoke exposure by cotinine determination in urine. The
      analytical procedure is simple and fast (20 min) when compared to other similar
      methods existing in the literature, and it is cheaper than the mass spectrometry
      techniques usually used to quantify levels in nonsmokers. We obtained a
      quantification limit of 12.30 MUg/L and a recovery of over 90%. The linearity
      ranges used were 12-250 and 250-4000 MUg/L. The method was successfully used to
      determine cotinine in urine samples collected from different volunteers and is
      clearly an alternative routine method that allows active and passive smokers to
      be distinguished. 

PMID- 24668724
TI  - The engineering of artificial cellular nanosystems using synthetic biology
      approaches.
AB  - Artificial cellular systems are minimal systems that mimic certain properties of
      natural cells, including signaling pathways, membranes, and metabolic pathways.
      These artificial cells (or protocells) can be constructed following a synthetic
      biology approach by assembling biomembranes, synthetic gene circuits, and cell
      free expression systems. As artificial cells are built from bottom-up using
      minimal and a defined number of components, they are more amenable to predictive
      mathematical modeling and engineered controls when compared with natural cells.
      Indeed, artificial cells have been implemented as drug delivery machineries and
      in situ protein expression systems. Furthermore, artificial cells have been used
      as biomimetic systems to unveil new insights into functions of natural cells,
      which are otherwise difficult to investigate owing to their inherent complexity.
      It is our vision that the development of artificial cells would bring forth
      parallel advancements in synthetic biology, cell-free systems, and in vitro
      systems biology. For further resources related to this article, please visit the
      WIREs website. Conflict of interests: The authors declare that they have no
      competing financial interests. 

PMID- 24668725
TI  - Targeting mitochondrial alterations to prevent type 2 diabetes--evidence from
      studies of dietary redox-active compounds.
AB  - As a growing epidemic, type 2 diabetes mellitus (T2DM) has significantly affected
      the individual's quality of life and economy of the society. Understanding the
      mechanisms of the disease and discovery of new therapeutic options has become
      more urgent than ever before. Mitochondrial alterations (e.g. functional
      alterations, and impaired biogenesis and dynamics) are strongly associated with
      the development of T2DM. Accumulation of reactive oxygen species or intermediates
      of incomplete fatty acid oxidation due to mitochondrial deficiency activates
      stress kinases and dampens insulin signaling. Redox-active compounds such as
      resveratrol, pyrroloquinoline quinone, and hydroxytyrosol can potently counteract
      reactive oxygen species, and improve mitochondrial function and biogenesis.
      Therefore, targeting the mitochondrial alterations with these redox-active
      compounds may lead to new therapeutic or preventive options for T2DM. In this
      article, we review the molecular mechanisms of mitochondrial alterations in T2DM,
      and the action of redox-active compounds to reverse mitochondrial changes and
      oxidative stress in T2DM. In addition, the current challenges and future
      directions are discussed and prospected. 

PMID- 24668726
TI  - Truncated CXCL10 is associated with failure to achieve spontaneous clearance of
      acute hepatitis C infection.
AB  - The pathogenesis of hepatitis C virus (HCV) infection is strongly influenced by
      the nature of the host's antiviral immunity. Counterintuitively, elevated serum
      concentrations of C-X-C chemokine 10 (CXCL10), a potent chemoattractant for
      antiviral T-cells and NK-cells, are associated with poor treatment outcomes in
      patients with chronic HCV. It has been reported that an N-terminal truncated form
      of CXCL10, generated by the protease dipeptidylpeptidase 4 (DPP4), can act as
      chemokine antagonist. We sought to investigate CXCL10 antagonism in the clinical
      outcome and evolution of acute HCV infection. We collected serial blood samples
      from 16 patients, at the clinical onset of acute HCV infection and at 12
      standardized follow-up timepoints over the first year. Intact and truncated
      CXCL10 and DPP4 activity were quantified in all longitudinal samples. In
      addition, NK-cell frequency/phenotype, and HCV-specific T-cell responses were
      assessed. Subjects developing chronicity (n = 11) had higher concentrations of
      CXCL10 (P < 0.001), which was predominantly in a truncated form (P = 0.036)
      compared to patients who spontaneously resolved infection (n = 5). Truncated
      CXCL10 correlated with HCV-RNA (r = 0.40, P < 0.001) and DPP4 activity (r = 0.53,
      P < 0.001). Subjects who resolved infection had a higher frequency of HCV
      specific interferon-gamma (IFNgamma)-producing T-cells (P = 0.017) and
      predominance of cytotoxic NK-cells (P = 0.005) compared to patients who became
      chronic. Patients who became persistently infected had higher proportions of
      cytokine-producing NK-cells, which were correlated with concentrations of
      truncated CXCL10 (r = 0.92, P < 0.001). CONCLUSION: This study provides the first
      evidence of chemokine antagonism during acute HCV infection. We suggest that the
      DPP4-CXCL10 axis inhibits antiviral innate and adaptive host immunity and favors
      establishment of viral persistence.

PMID- 24668727
TI  - A convenient photocatalytic fluorination of unactivated C-H bonds.
AB  - Fluorination reactions are essential to modern medicinal chemistry, thus
      providing a means to block site-selective metabolic degradation of drugs and
      access radiotracers for positron emission tomography imaging. Despite current
      sophistication in fluorination reagents and processes, the fluorination of
      unactivated C?H bonds remains a significant challenge. Reported herein is a
      convenient and economic process for direct fluorination of unactivated C?H bonds
      that exploits the hydrogen abstracting ability of a decatungstate photocatalyst
      in combination with the mild fluorine atom transfer reagent N
      fluorobenzenesulfonimide. This operationally straightforward reaction provides
      direct access to a wide range of fluorinated organic molecules, including
      structurally complex natural products, acyl fluorides, and fluorinated amino acid
      derivatives. 

PMID- 24668728
TI  - Disrupted network architecture of the resting brain in attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is one of the most
      prevalent psychiatric disorders of childhood. Neuroimaging investigations of ADHD
      have traditionally sought to detect localized abnormalities in discrete brain
      regions. Recent years, however, have seen the emergence of complementary lines of
      investigation into distributed connectivity disturbances in ADHD. Current models
      emphasize abnormal relationships between default network-involved in internally
      directed mentation and lapses of attention-and task positive networks, especially
      ventral attention network. However, studies that comprehensively investigate
      interrelationships between large-scale networks in ADHD remain relatively rare.
      METHODS: Resting state functional magnetic resonance imaging scans were obtained
      from 757 participants at seven sites in the ADHD-200 multisite sample. Functional
      connectomes were generated for each subject, and interrelationships between seven
      large-scale brain networks were examined with network contingency analysis.
      RESULTS: ADHD brains exhibited altered resting state connectivity between default
      network and ventral attention network [P < 0.0001, false discovery rate (FDR)
      corrected], including prominent increased connectivity (more specifically,
      diminished anticorrelation) between posterior cingulate cortex in default network
      and right anterior insula and supplementary motor area in ventral attention
      network. There was distributed hypoconnectivity within default network (P =
      0.009, FDR-corrected), and this network also exhibited significant alterations in
      its interconnections with several other large-scale networks. Additionally, there
      was pronounced right lateralization of aberrant default network connections.
      CONCLUSIONS: Consistent with existing theoretical models, these results provide
      evidence that default network-ventral attention network interconnections are a
      key locus of dysfunction in ADHD. Moreover, these findings contribute to growing
      evidence that distributed dysconnectivity within and between large-scale networks
      is present in ADHD.

PMID- 24668729
TI  - Role of dendritic cells in the context of acute cellular rejection: comparison
      between tacrolimus- or cyclosporine A-treated heart transplanted recipients.
AB  - BACKGROUND: In the last years many studies have been designed to predict risk of
      acute rejection and to adapt the immunosuppressive therapy. The importance of
      dendritic cells (DCs) in the immune response, especially their role in tolerance
      is known. Thus, we investigated the influence of tacrolimus (TAC)-based and of
      cyclosporine A (CsA)-based immunosuppressive therapies on dendritic cells and the
      incidence of rejection in heart transplant recipients. METHODS: Groups consisted
      of 14 CsA treated and 15 TAC treated patients. At different study time points (0,
      3 and 6 months after study begin) peripheral blood from the patients was drawn to
      analyse (1) blood concentration of CsA or TAC (trough value) and (2) percentages
      of plasmacytoid and myeloid DC (p and mDC) subsets using flow cytometry.
      Histological rejection grading was performed of endomyocardial biopsies. RESULTS:
      TAC treated patients had significantly higher values of pDCs (CsA group 53.9%+/
      13.0%; TAC group 67.5%+/-8.4%; p<0.05) and significantly lower values of mDCs
      than CsA treated patients (CsA group 58%+/-19.0%; TAC group 45.2%+/-10.7%;
      p<0.05). In general, HTx patients with rejection grade of >=2 had significant
      lower values of pDCs (55.1%+/-16.2%) compared to patients without rejection
      (63.6%+/-10.5%; p<0.05). TAC-treated patients had significantly less rejections
      CsA-treated patients (CsA group 0.86+/-0.95; TAC group 0.2+/-0.4; p<0.05).
      CONCLUSIONS: Our results showed that HTx patients with high pDCs had a lower risk
      for rejection and that TAC-treated patients had higher pDCs values compared to
      CsA-treated patients. Future studies need to define individual pDC values to
      predict acute cellular rejection.

PMID- 24668730
TI  - A primer of statistical methods for correlating parameters and properties of
      electrospun poly(L-lactide) scaffolds for tissue engineering--PART 2: regression.
AB  - This two-articles series presents an in-depth discussion of electrospun poly-L
      lactide scaffolds for tissue engineering by means of statistical methodologies
      that can be used, in general, to gain a quantitative and systematic insight about
      effects and interactions between a handful of key scaffold properties (Ys) and a
      set of process parameters (Xs) in electrospinning. While Part-1 dealt with the
      DOE methods to unveil the interactions between Xs in determining the
      morphomechanical properties (ref. Y1-4), this Part-2 article continues and
      refocuses the discussion on the interdependence of scaffold properties
      investigated by standard regression methods. The discussion first explores the
      connection between mechanical properties (Y4) and morphological descriptors of
      the scaffolds (Y1-3) in 32 types of scaffolds, finding that the mean fiber
      diameter (Y1) plays a predominant role which is nonetheless and crucially
      modulated by the molecular weight (MW) of PLLA. The second part examines the
      biological performance (Y5) (i.e. the cell proliferation of seeded bone marrow
      derived mesenchymal stromal cells) on a random subset of eight scaffolds vs. the
      mechanomorphological properties (Y1-4). In this case, the featured regression
      analysis on such an incomplete set was not conclusive, though, indirectly
      suggesting in quantitative terms that cell proliferation could not fully be
      explained as a function of considered mechanomorphological properties (Y1-4), but
      in the early stage seeding, and that a randomization effects occurs over time
      such that the differences in initial cell proliferation performance (at day 1) is
      smeared over time. The findings may be the cornerstone of a novel route to accrue
      sufficient understanding and establish design rules for scaffold biofunctional
      vs. architecture, mechanical properties, and process parameters.

PMID- 24668731
TI  - The effect of geometry on tumor thermal profile and its use in tumor functional
      state estimation.
AB  - Thermal differences between transplanted tumors and tumors in humans prevent the
      implementation of thermographic methods developed in mice models to human models
      and vise-versa. Transplantable tumors tend to have an extruding shape, which may
      affect the thermal patterns. This hypothesis was studied in phantom experiments
      and simulations. A correlation between tumor dimensions and relative temperature
      was found and used to estimate tumor functional state from previously published
      in vivo experiments. A correlation was found between temperature differences and
      tumor growth rates (tumor aggressiveness) and the effect of tumor treatment was
      demonstrated, showing the potential for in vivo, non-invasive tumor monitoring.

PMID- 24668733
TI  - Care of gastrostomy feeding tube in children with developmental disabilities.

PMID- 24668732
TI  - Thymic stromal lymphopoietin is expressed in the intact central nervous system
      and upregulated in the myelin-degenerative central nervous system.
AB  - Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine expressed at
      barrier surfaces of the skin, gut, nose, lung, and the maternal/fetal interphase.
      At these sites, it is important for the generation and maintenance of non
      inflammatory, tissue-resident dendritic cell responses. We show here that TSLP is
      also expressed in the central nervous system (CNS) where it is produced by
      choroid plexus epithelial cells and astrocytes in the spinal cord. Under
      conditions of low-grade myelin degeneration, the numbers of TSLP-expressing
      astrocytes increase, and microglia express transcripts for the functional TSLP
      receptor dimer indicating that these cells are targets for TSLP in the myelin
      degenerative CNS.

PMID- 24668734
TI  - Confidentiality Advisory Group already regulates use of non-anonymised patient
      data.

PMID- 24668737
TI  - Polyvinylimidazole/sol-gel composite as a novel solid-phase microextraction
      coating for the determination of halogenated benzenes from aqueous solutions.
AB  - A polyvinylimidazole/sol-gel composite is proposed as a novel solid-phase
      microextraction fiber to extract five halobenzenes from the headspace of aqueous
      solutions in combination with gas chromatography with mass spectrometry. The
      prepared fiber was characterized by scanning electron microscopy and Fourier
      transform infrared spectroscopy. The obtained results showed that porous
      polyvinylimidazole/sol-gel composite was chemically deposited on fused silica
      fiber. The effect of important extraction parameters including extraction
      temperature, extraction time, and salt content were investigated. The optimum
      conditions were as follows: extraction temperature 25 degrees C, extraction time
      20 min, and salt concentration 30 w/v%. Detection limits and relative standard
      deviations of the developed method for halogenated benzenes were below 0.1 pg/mL
      and 15%, respectively. Repeatability of the proposed method, explained by
      relative standard deviation, varied between 5.48 and 9.15% (n = 5). The limits of
      detection (S/N = 3) ranged between 0.01 and 0.10 ng/L using gas chromatography
      with mass spectrometry with selected ion monitoring mode. For real sample
      analysis, three types of water samples with different matrices (ground, surface,
      and tap water) were studied. The optimized procedure was applied to extraction
      and method validation of halogenated benzenes in spiked water samples. 

PMID- 24668738
TI  - Comparing the accuracy of ultrasound versus fluoroscopy in glenohumeral
      injections: a systematic review and meta-analysis.
AB  - OBJECTIVE: We performed a systematic review with meta-analysis to compare the
      accuracy of fluoroscopic-guided glenohumeral injections with that of ultrasound
      guided glenohumeral injections as reported in prior studies. METHODS: We reviewed
      the databases of MEDLINE, PubMed, and Google Scholar using combinations of the
      keywords "ultrasound," "fluoroscopy," "injection," and "shoulder" for articles
      reporting the injection accuracy, confirmed by imaging, of the first attempt
      under either fluoroscopic or ultrasound guidance. A meta-analysis was performed
      to assess the accuracy of fluoroscopic-guided glenohumeral injections versus
      ultrasound-guided glenohumeral injections. RESULTS: Five of 42 pertinent studies
      met our inclusion criteria for a total of 406 glenohumeral injections, of which
      115 were fluoroscopy-guided and 291 were ultrasound-guided. The meta-effect
      estimates for the proportion of joints successfully injected with ultrasound and
      fluoroscopic guidance were 93% (95% CI, 86% to 98%) and 80% (95% CI, 63% to 93%),
      respectively, which did not reach statistical significance (Q[df] = 2.55 [1], p =
      0.11). CONCLUSIONS: Our meta-analysis indicates that glenohumeral injections
      guided by ultrasound are more accurate than injections guided by fluoroscopy but
      this difference did not reach statistical significance. As the use of ultrasound
      does not expose the patient or practitioner to radiation, its similar accuracy
      may make it the preferred modality for image-guided glenohumeral joint
      injections. Limitations to our analysis include the retrospective nature, limited
      number of studies included, and the potential generalizability of our findings to
      regions outside of those included in our study.

PMID- 24668739
TI  - Suppression of autophagy during liver regeneration impairs energy charge and
      hepatocyte senescence in mice.
AB  - Autophagy is a homeostatic mechanism that regulates protein and organelle
      turnover and uses the amino acids from degraded proteins to produce adenosine 5'
      triphosphate (ATP). We investigated the activity of autophagy-associated pathways
      in liver regeneration after partial hepatectomy (PHx) in liver-specific autophagy
      related gene 5 (Atg5) knockout (KO) mice. Liver regeneration was severely
      impaired by 70% PHx, with a reduction in postoperative mitosis, but a
      compensating increase in hepatocyte size. PHx induced intracellular adenosine
      triphosphate and beta-oxidation reduction as well as injured cellular
      mitochondria. Furthermore, PHx in Atg5 KO mice enhanced hepatic accumulation of
      p62 and ubiquitinated proteins. These results indicated that reorganization of
      intracellular proteins and organelles during autophagy was impaired in the
      regenerating liver of these mice. Up-regulation of p21 was associated with
      hepatocyte senescence, senescence-associated beta-galactosidase expression,
      irreversible growth arrest, and secretion of senescence-associated molecules,
      including interleukin (IL)-6 and IL-8. CONCLUSION: These findings indicate that
      autophagy plays a critical role in liver regeneration and in the preservation of
      cellular quality, preventing hepatocytes from becoming fully senescent and
      hypertrophic.

PMID- 24668740
TI  - Safranal, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin
      signaling in C2C12 myotubes and improves glucose tolerance in diabetic KK-Ay
      mice.
AB  - SCOPE: Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin
      signaling by tyrosine dephosphorylation of insulin receptor, and its increased
      activity and expression is implicated in the pathogenesis of insulin resistance.
      Hence, PTP1B inhibition is anticipated to improve insulin resistance in type 2
      diabetic subjects. The aim of this study was to find a novel PTP1B inhibitor from
      medicinal food and to evaluate its antidiabetic effects. METHODS AND RESULTS: We
      found that saffron (Crocus sativus L.), which is used both as a spice and as a
      traditional medicine, potently inhibits PTP1B activity. Analyses of saffron
      extracts demonstrated that safranal, the saffron's aroma compound, is a principal
      PTP1B inhibitor, and induces a ligand-independent activation of insulin signaling
      in cultured myotubes. Our data implied that the molecular mechanism underlying
      the inactivation of PTP1B could be attributed to the covalent modification of the
      catalytic cysteinyl thiol by safranal through a Michael addition. Furthermore,
      safranal significantly enhanced glucose uptake through the translocation of
      glucose transporter 4. We also demonstrated that 2-wk oral administration of 20
      mg/kg/day safranal improved impaired glucose tolerance in type 2 diabetic KK-A(y)
      mice. CONCLUSION: Our results strongly suggest the usefulness of safranal in
      antidiabetic treatment for type 2 diabetic subjects.

PMID- 24668742
TI  - Properties and in vitro evaluation of high modulus biodegradable polyurethanes
      for applications in cardiovascular stents.
AB  - This study examined the suitability of a family of biodegradable polyurethanes
      (PUs) NovoSorb developed for the vascular stent application. These segmented PUs
      are formulated to be biodegradable using degradable polyester and PU blocks. A
      series of PUs comprising different hard segment weight percentage ranging from 60
      to 100 were investigated. The mechanical properties of the PUs were evaluated
      before and after gamma sterilization to assess their suitability for vascular
      implants. The real-time (PBS/37 degrees C/pH 7.4) hydrolytic degradation studies
      were carried out under sterile conditions and PU glass transition temperature,
      molecular weight, and mass loss at 3, 6, and 9 months were determined. The
      viability and growth of Human Umbilical Vein Endothelial Cells (HUVEC) on PU
      surfaces were determined to assess the effect of PU degradation. The effect of
      coating of extracellular matrix (ECM) components on cell viability was also
      investigated. The study showed that the PUs possess excellent mechanical
      properties exhibiting high tensile strength (41-56 MPa) and tensile modulus (897
      1496 MPa). The PU films maintained mechanical strength during the early phase of
      the degradation but lost strength at latter stages. The unmodified polymer
      surface of each PU promotes endothelial cell growth and proliferation, with a
      HUVEC retention rate of >70%.

PMID- 24668741
TI  - Efficient solid-phase synthesis of pppRNA by using product-specific labeling.
AB  - A novel solid-phase synthesis and purification strategy for 5'-triphosphate
      oligonucleotides by using lipophilic tagging of the triphosphate moiety is
      reported. This is based on triphosphate synthesis with 5'-O-cyclotriphosphate
      intermediates, whereby a lipophilic tag, such as decylamine, is introduced during
      the ring-opening reaction to give a linear gamma-phosphate-tagged species. This
      method enables the highly efficient synthesis of 5'-triphosphorylated RNA
      derivatives and their gamma-phosphate-substituted analogues and will especially
      facilitate the advancement of therapeutic approaches that make use of 5'
      triphosphate oligonucleotides as potent activators of the cytosolic immune sensor
      RIG-I. 

PMID- 24668743
TI  - Obesity, traumatic brain injury, childhood abuse, and suicide attempts in females
      at risk.
AB  - PURPOSE: This study tested the hypothesis that obesity is related to history of
      traumatic brain injury (TBI), severity and frequency of childhood physical (CPA)
      and sexual abuse (CSA), and suicide attempts, adjusting for related variables in
      a high risk female population. DESIGN: This cross-sectional study of 81 females
      compared obese to non-obese. METHODS: All variables were verified by private
      interviews, physical examination, and documented evidence, then statistically
      analyzed with logistic regression. FINDINGS: Obesity at the time of interview was
      related to history of a decreased number of TBIs per person, greater CSA, suicide
      attempts, and decreased CPA, adjusting for current smoking, depression, currently
      using selective serotonin reuptake inhibitors, and age. CONCLUSIONS: Number of
      TBIs per person and CPA were inversely related to obesity, adjusting for related
      variables. Greater CSA frequency and severity, and having attempted suicide were
      significantly related to greater risk of obesity, adjusting for related
      variables. Though causes of obesity cannot be determined by this design, and
      findings should be viewed with caution, this study provides new insight into the
      obesity epidemic that requires further investigation. CLINICAL RELEVANCE:
      Rehabilitation nurses are in ideal settings when patient's conditions are less
      acute, providing opportunities to address complex serious underlying etiologies
      of obesity. Obesity has not been alleviated by teaching about diet and exercise
      because obesity may be the result of dietary self-medication of pain from
      previous experiences. CSA is a very serious problem that could precipitate
      suicide attempts, obesity, and multifaceted poor health outcomes throughout the
      life span; subsequently placing individuals at greater risk of requiring
      rehabilitation services.

PMID- 24668744
TI  - The realm of vitamin K dependent proteins: shifting from coagulation toward
      calcification.
AB  - In the past few decades vitamin K has emerged from a single-function "haemostasis
      vitamin" to a "multi-function vitamin." The use of vitamin K antagonists (VKA)
      inevitably showed that the inhibition was not restricted to vitamin K dependent
      coagulation factors but also synthesis of functional extrahepatic vitamin K
      dependent proteins (VKDPs), thereby eliciting undesired side effects. Vascular
      calcification is one of the recently revealed detrimental effects of VKA. The
      discovery that VKDPs are involved in vascular calcification has propelled our
      mechanistic understanding of this process and has opened novel avenues for
      diagnosis and treatment. This review addresses mechanisms of VKDPs and their
      significance for physiological and pathological calcification. 

PMID- 24668745
TI  - A duplicated NUCLEOLIN gene with antagonistic activity is required for chromatin
      organization of silent 45S rDNA in Arabidopsis.
AB  - In plants as well as in animals, hundreds to thousands of 45S rRNA gene copies
      localize in Nucleolus Organizer Regions (NORs), and the activation or repression
      of specific sets of rDNA depends on epigenetic mechanisms. Previously, we
      reported that the Arabidopsis thaliana nucleolin protein NUC1, an abundant and
      evolutionarily conserved nucleolar protein in eukaryotic organisms, is required
      for maintaining DNA methylation levels and for controlling the expression of
      specific rDNA variants in Arabidopsis. Interestingly, in contrast with animal or
      yeast cells, plants contain a second nucleolin gene. Here, we report that
      Arabidopsis NUC1 and NUC2 nucleolin genes are both required for plant growth and
      survival and that NUC2 disruption represses flowering. However, these genes seem
      to be functionally antagonistic. In contrast with NUC1, disruption of NUC2
      induces CG hypermethylation of rDNA and NOR association with the nucleolus.
      Moreover, NUC2 loss of function triggers major changes in rDNA spatial
      organization, expression, and transgenerational stability. Our analyses indicate
      that silencing of specific rRNA genes is mostly determined by the active or
      repressed state of the NORs and that nucleolin proteins play a key role in the
      developmental control of this process. 

PMID- 24668746
TI  - Fast retrograde signaling in response to high light involves metabolite export,
      MITOGEN-ACTIVATED PROTEIN KINASE6, and AP2/ERF transcription factors in
      Arabidopsis.
AB  - Regulation of the expression of nuclear genes encoding chloroplast proteins
      allows for metabolic adjustment in response to changing environmental conditions.
      This regulation is linked to retrograde signals that transmit information on the
      metabolic state of the chloroplast to the nucleus. Transcripts of several
      APETALA2/ETHYLENE RESPONSE FACTOR transcription factors (AP2/ERF-TFs) were found
      to respond within 10 min after transfer of low-light-acclimated Arabidopsis
      thaliana plants to high light. Initiation of this transcriptional response was
      completed within 1 min after transfer to high light. The fast responses of four
      AP2/ERF genes, ERF6, RRTF1, ERF104, and ERF105, were entirely deregulated in
      triose phosphate/phosphate translocator (tpt) mutants. Similarly, activation of
      MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) was upregulated after 1 min in the wild
      type but not in the tpt mutant. Based on this, together with altered transcript
      regulation in mpk6 and erf6 mutants, a retrograde signal transmission model is
      proposed starting with metabolite export through the triose phosphate/phosphate
      translocator with subsequent MPK6 activation leading to initiation of AP2/ERF-TF
      gene expression and other downstream gene targets. The results show that
      operational retrograde signaling in response to high light involves a metabolite
      linked pathway in addition to previously described redox and hormonal pathways. 

PMID- 24668747
TI  - Chloroplast DNA in mature and senescing leaves: a reappraisal.
AB  - The fate of plastid DNA (ptDNA) during leaf development has become a matter of
      contention. Reports on little change in ptDNA copy number per cell contrast with
      claims of complete or nearly complete DNA loss already in mature leaves. We
      employed high-resolution fluorescence microscopy, transmission electron
      microscopy, semithin sectioning of leaf tissue, and real-time quantitative PCR to
      study structural and quantitative aspects of ptDNA during leaf development in
      four higher plant species (Arabidopsis thaliana, sugar beet [Beta vulgaris],
      tobacco [Nicotiana tabacum], and maize [Zea mays]) for which controversial
      findings have been reported. Our data demonstrate the retention of substantial
      amounts of ptDNA in mesophyll cells until leaf necrosis. In ageing and senescent
      leaves of Arabidopsis, tobacco, and maize, ptDNA amounts remain largely unchanged
      and nucleoids visible, in spite of marked structural changes during chloroplast
      to-gerontoplast transition. This excludes the possibility that ptDNA degradation
      triggers senescence. In senescent sugar beet leaves, reduction of ptDNA per cell
      to ~30% was observed reflecting primarily a decrease in plastid number per cell
      rather than a decline in DNA per organelle, as reported previously. Our findings
      are at variance with reports claiming loss of ptDNA at or after leaf maturation. 

PMID- 24668748
TI  - On the fate of plastid DNA molecules during leaf development: response to the
      Golczyk et al. Commentary.

PMID- 24668750
TI  - SDF-1alpha induces differential trafficking of CXCR4-CXCR7 involving cyclophilin
      A, CXCR7 ubiquitination and promotes platelet survival.
AB  - Platelet-derived SDF-1alpha (CXCL12) mediates inflammatory and regenerative
      mechanisms. The present study characterizes the effect of SDF-1alpha ligation in
      platelets. SDF-1alpha (0-100 MUM) dose and time dependently caused
      internalization of its receptor CXCR4 (28.9 +/- 1.6 vs. 16.1 +/- 1.9 in SDF
      1alpha-treated platelets), coupled to the surface externalization of CXCR7 (65.5
      +/- 8 vs. 162.8 +/- 27.6 following SDF-1alpha treatment), both in vitro and in
      vivo. This was inhibited in the presence of AMD3100 (100 MUM), CXCR4 blocking and
      vesicular transport inhibitors (brefeldin A, 10 MUM; rapamycin, 100 nM). SDF
      1alpha/CXCR-4-mediated CXCR7 translocation was significantly reduced by
      inhibitors of ERK1/2-(U0126-10 MUM) and cyclophilinA (CyPA)-(NIM811-10 MUM) by 28
      and 46%, respectively. Further, SDF-1alpha-induced downstream phosphorylation of
      Erk1/2 led to CyPA-dependent ubiquitination of CXCR7, which is essential for its
      surface translocation. CyPA-PPIase-activity inhibitor NIM-811, Erk1/2, and E1
      ligase inhibitor-(PYR-41-25 MUM) significantly abolished SDF-1alpha-driven CXCR7
      ubiquitination and subsequent surface translocation. SDF-1alpha induced CXCR7
      ubiquitination, and its surface exposure was observed in wild-type murine
      platelets, but not in CyPA-deficient platelets. SDF-1alpha/CXCR4-CyPA-dependent
      CXCR7 translocation and its subsequent ligation attenuated activation-induced
      apoptosis both in vitro and when administered in vivo. This antiapoptotic effect
      of SDF-1alpha was abrogated by blocking CXCR7, also significantly affected in
      Cypa(-/-) platelets. Thus, we decipher a novel mechanism, whereby SDF-1alpha
      regulates relative receptor availability in circulating platelets and exerts its
      prosurvival benefits.-Chatterjee, M., Seizer, P., Borst, O., Schonberger, T.,
      Mack, A., Geisler, T., Langer, H. F., May, A. E., Vogel, S., Lang, F., Gawaz, M.
      SDF-1alpha induces differential trafficking of CXCR4-CXCR7 involving cyclophilin
      A, CXCR7 ubiquitination and promotes platelet survival.

PMID- 24668749
TI  - Jasmonate-activated MYC2 represses ETHYLENE INSENSITIVE3 activity to antagonize
      ethylene-promoted apical hook formation in Arabidopsis.
AB  - The apical hook is an essential structure that enables epigeal plants to protrude
      through the soil. Arabidopsis thaliana HOOKLESS1 (HLS1) is reported to be a key
      regulator of hook development and a direct target gene of the ethylene (ET)
      activated transcription factors ETHYLENE INSENSITIVE3 (EIN3) and its close
      homolog EIN3-Like1. Previous research has shown that the phytohormones jasmonate
      (JA) and ET antagonistically regulate apical hook development, although the
      underlying molecular mechanism is largely unknown. Here, we report that JA
      represses hook formation by reducing HLS1 expression. Our results further reveal
      that the JA-activated transcription factor MYC2 represses EIN3 function to reduce
      HLS1 expression through at least the following two layers of regulation: (1) MYC2
      binds to the promoter of an F-box gene, EIN3 BINDING F-BOX PROTEIN1, to induce
      its expression and thus promote EIN3 degradation; and (2) MYC2 physically
      interacts with EIN3 and inhibits its DNA binding activity. Collectively, our
      findings shed light on the molecular mechanism underlying the antagonism between
      JA and ET during apical hook development and provide insight into the coaction of
      multiple phytohormones in the regulation of plant growth and development. 

PMID- 24668751
TI  - Vascular characterization of mice with endothelial expression of cytochrome P450
      4F2.
AB  - Cytochrome P450 (CYP) 4A and 4F enzymes metabolize arachidonic acid to 20
      hydroxyeicosatetraenoic acid (20-HETE). Although CYP4A-derived 20-HETE is known
      to have prohypertensive and proangiogenic properties, the effects of CYP4F
      derived metabolites are not well characterized. To investigate the role of CYP4F2
      in vascular disease, we generated mice with endothelial expression of human
      CYP4F2 (Tie2-CYP4F2-Tr). LC/MS/MS analysis revealed 2-foldincreases in 20-HETE
      levels in tissues and endothelial cells (ECs), relative to wild-type (WT)
      controls. Tie2-CYP4F2-Tr ECs demonstrated increases in growth (267.1 +/- 33.4 vs.
      205.0 +/- 13% at 48 h) and tube formation (7.7 +/- 1.1 vs. 1.6 +/- 0.5
      tubes/field) that were 20-HETE dependent and associated with up-regulation of
      prooxidant NADPH oxidase and proangiogenic VEGF. Increases in VEGF and NADPH
      oxidase levels were abrogated by inhibitors of NADPH oxidase and MAPK,
      respectively, suggesting the possibility of crosstalk between pathways.
      Interestingly, IL-6 levels in Tie2-CYP4F2-Tr mice (18.6 +/- 2.7 vs. 7.9 +/- 2.7
      pg/ml) were up-regulated via NADPH oxidase- and 20-HETE-dependent mechanisms.
      Although Tie2-CYP4F2-Tr aortas displayed increased vasoconstriction,
      vasorelaxation and blood pressure were unchanged. Our findings indicate that
      human CYP4F2 significantly increases 20-HETE production, CYP4F2-derived 20-HETE
      mediates EC proliferation and angiogenesis via VEGF- and NADPH oxidase-dependent
      manners, and the Tie2-CYP4F2-Tr mouse is a novel model for examining the
      pathophysiological effects of CYP4F2-derived 20-HETE in the vasculature.-Cheng,
      J., Edin, M. L., Hoopes, S. L., Li, H., Bradbury, J. A., Graves, J. P., DeGraff,
      L. M., Lih, F. B., Garcia, V., Shaik, J. S. B., Tomer, K. B., Flake, G. P.,
      Falck, J. R., Lee, C. R., Poloyac, S. M., Schwartzman, M. L., Zeldin, D. C.
      Vascular characterization of mice with endothelial expression of cytochrome P450
      4F2.

PMID- 24668752
TI  - The alternative complement pathway regulates pathological angiogenesis in the
      retina.
AB  - A defining feature in proliferative retinopathies is the formation of
      pathological neovessels. In these diseases, the balance between neovessel
      formation and regression determines blindness, making the modulation of neovessel
      growth highly desirable. The role of the immune system in these retinopathies is
      of increasing interest, but it is not completely understood. We investigated the
      role of the alternative complement pathway during the formation and resolution of
      aberrant neovascularization. We used alternative complement pathway-deficient
      (Fb(-/-)) mice and age- and strain-matched control mice to assess neovessel
      development and regression in an oxygen-induced retinopathy (OIR) mouse model. In
      the control mice, we found increased transcription of Fb after OIR treatment. In
      the Fb(-/-) mice, we prepared retinal flatmounts and identified an increased
      number of neovessels, peaking at postnatal day 17 (P17; P=0.001). Subjecting
      human umbilical vein endothelial cells (HUVECs) to low oxygen, mimicking a
      characteristic of neovessels, decreased the expression of the complement
      inhibitor Cd55. Finally, using laser capture microdissection (LCM) to isolate the
      neovessels after OIR, we found decreased expression of Cd55 (P=0.005). Together,
      our data implicate the alternative complement pathway in facilitating neovessel
      clearance by down-regulating the complement inhibitor Cd55 specifically on
      neovessels, allowing for their targeted removal while leaving the established
      vasculature intact.-Sweigard, J. H., Yanai, R., Gaissert, P., Saint-Geniez, M.,
      Kataoka, K., Thanos, A., Stahl, G. L., Lambris, J. D., Connor, K. M. The
      alternative complement pathway regulates pathological angiogenesis in the retina.

PMID- 24668753
TI  - Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates
      their resistance to chemotherapy and irradiation.
AB  - iASPP is a member of the apoptosis-stimulating proteins of p53 (ASPP) family and
      negatively regulates the apoptotic function of p53. In a hematopoietic system,
      overexpression of iASPP results in blockage of apoptosis, which may play a role
      in regulating hematopoietic stem cell (HSC) numbers. To address this, we first
      analyzed the expression of iASPP in patients with acute leukemia (AL) and found
      it was highly expressed in patients with AL. We further established a transgenic
      mouse model in which human iASPP was specifically expressed in hematopoietic
      cells. Overexpression of iASPP led to an increase in the proportion of long-term
      HSCs, short-term HSCs, multipotent progenitors, and common myeloid progenitor.
      HSCs from iASPP transgenic mice had an advantage in long-term reconstitution
      potential. In addition, the hematopoietic cells from iASPP transgenic mice
      exhibited a significantly lower level of p53 dependent apoptosis. After
      irradiation damage, hematopoietic cells of iASPP transgenic mice had a higher
      level of gamma-H2AX expression, which lasted for a longer time. These results
      provide the first evidence that the iASPP can increase HSC populations and
      reconstitution capacity. Interestingly, in response to cell damage stimuli,
      hematopoietic cells can be protected against apoptosis by iASPP; meanwhile these
      apoptosis-resistant cells would have more mutation accumulation, which might be
      the potential risk for malignant transformation.-Jia, Y., Peng, L., Rao, Q.,
      Xing, H., Huai, L., Yu, P., Chen, Y., Wang, C., Wang, M., Mi, Y., Wang, J.
      Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates
      their resistance to chemotherapy and irradiation. 

PMID- 24668755
TI  - Skull defects, alopecia, hypertelorism, and notched alae nasi caused by
      homozygous ALX4 gene mutation.

PMID- 24668756
TI  - Fast ultrasound-assisted extraction followed by capillary gas chromatography
      combined with nitrogen-phosphorous selective detector for the trace determination
      of tebuconazole in garlic, soil and water samples.
AB  - A fast and an efficient ultrasound-assisted extraction technique using a lower
      density extraction solvent than water was developed for the trace-level
      determination of tebuconazole in garlic, soil and water samples followed by
      capillary gas chromatography combined with nitrogen-phosphorous selective
      detector (GC-NPD). In this approach, ultrasound radiation was applied to
      accelerate the emulsification of the ethyl acetate in aqueous samples to enhance
      the extraction efficiency of tebuconazole without requiring extra partitioning or
      cleaning, and the use of capillary GC-NPD was a more sensitive detection
      technique for organonitrogen pesticides. The experimental results indicate an
      excellent linear relationship between peak area and concentration obtained in the
      range 1-50 MUg/kg or MUg/L. The limit of detection (S/N, 3 +/- 0.5) and limit of
      quantification (S/N, 7.5 +/- 2.5) were obtained in the range 0.2-3 and 1-10
      MUg/kg or MUg/L. Good spiked recoveries were achieved from ranges 95.55-101.26%,
      96.28-99.33% and 95.04-105.15% in garlic, Nanivaliyal soil and Par River water,
      respectively, at levels 5 and 20 MUg/kg or MUg/L, and the method precision (%
      RSD) was <=5%. Our results demonstrate that the proposed technique is a viable
      alternative for the determination of tebuconazole in complex samples. 

PMID- 24668754
TI  - RORalpha and ROR gamma are expressed in human skin and serve as receptors for
      endogenously produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D.
AB  - RORalpha and RORgamma are expressed in human skin cells that produce the
      noncalcemic 20-hydroxyvitamin D3 [20(OH)D3] and 20,23-dihydroxyvitamin D3
      [20,23(OH)2D3]. Chinese hamster ovary (CHO) cells stably expressing a Tet-on
      RORalpha or RORgamma expression vector and a ROR-responsive element (RORE)-LUC
      reporter, and a mammalian 2-hybrid model examining the interaction between the
      ligand binding domain (LBD) of RORalpha or RORgamma with an LBD-interacting LXXLL
      peptide, were used to study ROR-antagonist activities. These assays revealed that
      20(OH)D3 and 20,23(OH)2D3 function as antagonists of RORalpha and RORgamma.
      Moreover, 20(OH)D3 inhibited the activation of the promoter of the Bmal1 and
      G6pase genes, targets of RORalpha, and 20(OH)D3 and 20,23(OH)2D3 inhibited Il17
      promoter activity in Jurkat cells overexpressing RORalpha or RORgamma. Molecular
      modeling using crystal structures of the LBDs of RORalpha and RORgamma revealed
      docking scores for 20(OH)D3, 20,23(OH)2D3 and 1,25(OH)2D3 similar to those of the
      natural ligands, predicting good binding to the receptor. Notably, 20(OH)D3,
      20,23(OH)2D3, and 1,25(OH)2D3 inhibited RORE-mediated activation of a reporter in
      keratinocytes and melanoma cells and inhibited IL-17 production by immune cells.
      Our study identifies a novel signaling pathway, in which 20(OH)D3 and
      20,23(OH)2D3 act as antagonists or inverse agonists of RORalpha and RORgamma,
      that opens new possibilities for local (skin) or systemic regulation.-Slominski,
      A. T., Kim, T.-K., Takeda, Y., Janjetovic, Z., Brozyna, A. A., Skobowiat, C.,
      Wang, J., Postlethwaite, A., Li, W., Tuckey, R. C., Jetten, A. M. RORalpha and
      ROR gamma are expressed in human skin and serve as receptors for endogenously
      produced noncalcemic 20-hydroxy- and 20,23-dihydroxyvitamin D. 

PMID- 24668757
TI  - Changes in implementation of two evidence-based psychotherapies for PTSD in VA
      residential treatment programs: a national investigation.
AB  - There has been little investigation of the natural course of evidence-based
      treatments (EBTs) over time following the draw-down of initial implementation
      efforts. Thus, we undertook qualitative interviews with the providers at 38 U.S.
      Department of Veterans Affairs' residential treatment programs for posttraumatic
      stress disorder (PTSD) to understand implementation and adaptation of 2 EBTs,
      prolonged exposure (PE), and cognitive processing therapy (CPT), at 2 time points
      over a 4-year period. The number of providers trained in the therapies and level
      of training improved over time. At baseline, of the 179 providers eligible per VA
      training requirements, 65 (36.4%) had received VA training in PE and 111 (62.0%)
      in CPT with 17 (9.5%) completing case consultation or becoming national trainers
      in both PE and CPT. By follow-up, of the increased number of 190 eligible
      providers, 87 (45.8%) had received VA training in PE and 135 (71.1%) in CPT, with
      69 (36.3%) and 81 (42.6%) achieving certification, respectively. Twenty-two
      programs (57.9%) reported no change in PE use between baseline and follow-up,
      whereas 16 (42.1%) reported an increase. Twenty-four (63.2%) programs reported no
      change in their use of CPT between baseline and follow-up, 12 (31.6%) programs
      experienced an increase, and 2 (5.2%) programs experienced a decrease in use. A
      significant number of providers indicated that they made modifications to the
      manuals (e.g., tailoring, lengthening). Reasons for adaptations are discussed.
      The need to dedicate time and resources toward the implementation of EBTs is
      noted. 

PMID- 24668758
TI  - Stability, across environments, of grain and alcohol yield, in soft wheat
      varieties grown for grain distilling or bioethanol production.
AB  - BACKGROUND: Soft-milling wheat has potential use for both grain whisky distilling
      and bioethanol production. Varietal comparisons over wide-ranging environments
      would permit assessment of both grain and alcohol yield potential and also permit
      the stability across environments, for these parameters, to be compared. RESULTS:
      For 12 varieties, analysis of variance showed highly significant effects of
      variety, site, season and fertiliser application on grain and alcohol yield.
      There were also significant interactions between these factors and, consequently,
      varieties varied in stability across environments as well as in mean values for
      the parameters assessed. Alcohol production per hectare was affected more
      strongly by variation in grain yield than alcohol yield, but increasing grain
      protein content reduced alcohol yield and, therefore, utility for grain
      distilling. CONCLUSION: To maximise energy production, the best varieties for
      bioethanol would combine high and stable grain yield with slower reduction of
      alcohol yield as grain protein increases. For grain distilling, where the energy
      balance is less important, high alcohol yield will remain the key factor. Data
      derived using near infrared spectroscopy can be valuable in assessing stability
      of quality traits across environments.

PMID- 24668761
TI  - Bidirectional chemical communication between nanomechanical switches.
AB  - The interplay of biological machines depends critically on the bidirectionality
      of chemical information exchange. The implementation of such a communication
      procedure for abiological systems is achieved using two nanoswitches that both
      operate as transmitters and receivers by transfering copper ions in oxidation
      states +I and +II. Even at micromolar concentrations, communication in both
      directions is remarkably fast, occurring at t1/2 =2-3 min. Metal ion
      translocation triggers a 20 A relocation of the toggle at both nanoswitches,
      entailing major geometric and electronic changes.

PMID- 24668759
TI  - Mechanosensitivity may be enhanced in skeletal muscles of spinal cord-injured
      versus able-bodied men.
AB  - We investigated the effects of an acute bout of neuromuscular electrical
      stimulation-induced resistance exercise (NMES-RE) on intracellular signaling
      pathways involved in translation initiation and mechanical loading-induced muscle
      hypertrophy in spinal cord-injured (SCI) versus able-bodied (AB) individuals. AB
      and SCI individuals completed 90 isometric knee extension contractions at 30% of
      maximum voluntary or evoked contraction, respectively. Muscle biopsies were
      collected before, and 10 and 60 min after NMES-RE. Protein levels of alpha7- and
      beta1-integrin, phosphorylated and total GSK-3alpha/beta, S6K1, RPS6, 4EBP1, and
      FAK were assessed by immunoblotting. SCI muscle appears to be highly sensitive to
      muscle contraction even several years after the injury, and in fact it may be
      more sensitive to mechanical stress than AB muscle. Heightened signaling
      associated with muscle mechanosensitivity and translation initiation in SCI
      muscle may be an attempted compensatory response to offset elevated protein
      degradation in atrophied SCI muscle. .

PMID- 24668760
TI  - Effects of ketamine on explicit and implicit suicidal cognition: a randomized
      controlled trial in treatment-resistant depression.
AB  - BACKGROUND: Preliminary evidence suggests intravenous ketamine has rapid effects
      on suicidal cognition, making it an attractive candidate for depressed patients
      at imminent risk of suicide. In the first randomized controlled trial of ketamine
      using an anesthetic control condition, we tested ketamine's acute effects on
      explicit suicidal cognition and a performance-based index of implicit suicidal
      cognition (Implicit Association Test; IAT) previously linked to suicidal
      behavior. METHOD: Symptomatic patients with treatment-resistant unipolar major
      depression (inadequate response to >=3 antidepressants) were assessed using a
      composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation,
      Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive
      Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures
      were taken at baseline and 24 hr following a single subanesthetic dose of
      ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected
      for its similar, rapid anesthetic effects. Twenty four hours postinfusion,
      explicit suicidal cognition was significantly reduced in the ketamine but not the
      midazolam group. RESULTS: Fifty three percent of ketamine-treated patients scored
      zero on all three explicit suicide measures at 24 hr, compared with 24% of the
      midazolam group (chi(2) = 4.6; P = .03). Implicit associations between self- and
      escape-related words were reduced following ketamine (P = .01; d = .58) but not
      midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal
      cognition were largest in patients with elevated suicidal cognition at baseline,
      and were mediated by decreases in nonsuicide-related depressive symptoms.
      CONCLUSIONS: Intravenous ketamine produces rapid reductions in suicidal cognition
      over and above active placebo. Further study is warranted to test ketamine's
      antisuicidal effects in higher-risk samples.

PMID- 24668762
TI  - Multiplicative by nature: Logarithmic transformation in allometry.
AB  - The traditional allometric method, which is at the heart of research paradigms
      used by comparative biologists around the world, entails fitting a straight line
      to logarithmic transformations of the original bivariate data and then back
      transforming the resulting equation to form a two-parameter power function in the
      arithmetic scale. The method has the dual advantages of enabling investigators to
      fit statistical models that describe multiplicative growth while simultaneously
      addressing the multiplicative nature of residual variation in response variables
      (heteroscedasticity). However, important assumptions of the traditional method
      seldom are assessed in contemporary practice. When the assumptions are not met,
      mean functions may fail to capture the dominant pattern in the original data and
      incorrect form for error may be imposed upon the fitted model. A worked example
      from metabolic allometry in doves and pigeons illustrates both the power of newer
      statistical procedures and limitations of the traditional allometric method.

PMID- 24668764
TI  - Sitting during consultations encourages higher order thinking.

PMID- 24668763
TI  - Endogenous annexin A1 is a novel protective determinant in nonalcoholic
      steatohepatitis in mice.
AB  - Annexin A1 (AnxA1) is an effector of the resolution of inflammation and is highly
      effective in terminating acute inflammatory responses. However, its role in
      chronic settings is less investigated. Because changes in AnxA1 expression within
      adipose tissue characterize obesity in mice and humans, we queried a possible
      role for AnxA1 in the pathogenesis of nonalcoholic steatohepatitis (NASH), a
      disease commonly associated with obesity. NASH was induced in wild-type (WT) and
      AnxA1 knockout (AnxA1 KO) C57BL/6 mice by feeding a methionine-choline deficient
      (MCD) diet up to 8 weeks. In MCD-fed WT mice, hepatic AnxA1 increased in parallel
      with progression of liver injury. This mediator was also detected in liver
      biopsies from patients with NASH and its degree of expression inversely
      correlated with the extent of fibrosis. In both humans and rodents, AnxA1
      production was selectively localized in liver macrophages. NASH in AnxA1 KO mice
      was characterized by enhanced lobular inflammation resulting from increased
      macrophage recruitment and exacerbation of the M1 phenotype. Consistently, in
      vitro addition of recombinant AnxA1 to macrophages isolated from NASH livers down
      modulated M1 polarization through stimulation of interleukin-10 production.
      Furthermore, the degree of hepatic fibrosis was enhanced in MCD-fed AnxA1 KO
      mice, an effect associated with augmented liver production of the profibrotic
      lectin, galectin-3. Accordingly, AnxA1 addition to isolated hepatic macrophages
      reduced galectin-3 expression. CONCLUSIONS: Macrophage-derived AnxA1 plays a
      functional role in modulating hepatic inflammation and fibrogenesis during NASH
      progression, suggesting the possible use of AnxA1 analogs for therapeutic control
      of this disease.

PMID- 24668765
TI  - Activities of daily living and self-care agency in patients with multiple
      sclerosis for the first 10 years.
AB  - PURPOSE: The aim of the study was to present the effects of the disease and
      analyze the relationship between activities of daily living (ADL) and self-care
      in multiple sclerosis (MS) patients who have had the disease for the first 10
      years. DESIGN: This study was a descriptive cross-sectional study. METHODS: A
      total of 67 patients who fit the inclusion criteria of the study and volunteered
      to participate were included in the sample. Data were collected using the
      Exercise of Self-Care Agency Scale and the Barthel Index. FINDINGS: The mean age
      was 38.43+/-9.92. There was a statistically significant correlation between
      participants'educational backgrounds and self-care scores and between disease
      duration and Barthel index score (p<.05). CONCLUSIONS: The self-care levels of
      patients who have had MS for the first 10 years are medium, and they tend to be
      mildly dependent in performing their ADL. The duration of MS is positively
      correlated with level of ADL. CLINICAL RELEVANCE: In this study, it was shown
      that the duration of the disease in MS patients should be taken into account by
      rehabilitation nurses to implement effective nursing care.

PMID- 24668766
TI  - Real-time in vivo quantitative monitoring of drug release by dual-mode magnetic
      resonance and upconverted luminescence imaging.
AB  - Insufficient or excess drug doses, due to unknown actual drug concentrations at
      the focus, are one of the main causes of chemotherapy failure for cancers. In
      this regard, the real-time monitoring of the release of anticancer drugs from
      nanoparticle drug delivery systems is of crucial importance, but it remains a
      critical and unsolved challenge. Herein, we report the proposal and development
      of a novel concept of real-time monitoring of NIR-triggered drug release in vitro
      and in vivo by using simultaneous upconverted luminescence (UCL) and magnetic
      resonance (MR) imaging. Such a monitoring strategy features the high sensitivity
      of UCL and the high-resolution, noninvasiveness, and tissue-depth-independence of
      MR imaging. The dual-mode real-time and quantitative monitoring of drug release
      can be applied to determine online the drug concentrations in vivo in the tissue
      regions of interest and, therefore, to avoid insufficient or excess drug dosings.

PMID- 24668767
TI  - A pilot study of a randomized controlled trial of yoga as an intervention for
      PTSD symptoms in women.
AB  - Posttraumatic stress disorder (PTSD) is a debilitating condition that affects
      approximately 10% of women in the United States. Although effective
      psychotherapeutic treatments for PTSD exist, clients with PTSD report additional
      benefits of complementary and alternative approaches such as yoga. In particular,
      yoga may downregulate the stress response and positively impact PTSD and comorbid
      depression and anxiety symptoms. We conducted a pilot study of a randomized
      controlled trial comparing a 12-session Kripalu-based yoga intervention with an
      assessment control group. Participants included 38 women with current full or
      subthreshold PTSD symptoms. During the intervention, yoga participants showed
      decreases in reexperiencing and hyperarousal symptoms. The assessment control
      group, however, showed decreases in reexperiencing and anxiety symptoms as well,
      which may be a result of the positive effect of self-monitoring on PTSD and
      associated symptoms. Between-groups effect sizes were small to moderate (0.08
      0.31). Although more research is needed, yoga may be an effective adjunctive
      treatment for PTSD. Participants responded positively to the intervention,
      suggesting that it was tolerable for this sample. Findings underscore the need
      for future research investigating mechanisms by which yoga may impact mental
      health symptoms, gender comparisons, and the long-term effects of yoga practice. 

PMID- 24668768
TI  - Respiratory assessment in centronuclear myopathies.
AB  - The centronuclear myopathies (CNMs) are a group of inherited neuromuscular
      disorders classified as congenital myopathies. While several causative genes have
      been identified, some patients do not harbor any of the currently known
      mutations. These diverse disorders have common histological features, which
      include a high proportion of centrally nucleated muscle fibers, and clinical
      attributes of muscle weakness and respiratory insufficiency. Respiratory problems
      in CNMs may manifest initially during sleep, but daytime symptoms, ineffective
      airway clearance, and hypoventilation predominate as more severe respiratory
      muscle dysfunction evolves. Respiratory muscle capacity can be evaluated using a
      variety of clinical tests selected with consideration for the age and baseline
      motor function of the patient. Similar clinical tests of respiratory function can
      also be incorporated into preclinical CNM canine models to offer insight for
      clinical trials. Because respiratory problems account for significant morbidity
      in patients, routine assessments of respiratory muscle function are discussed.

PMID- 24668770
TI  - Changes of seasonal morph development induced by surgical operations in pupae of
      the large map butterfly Araschnia burejana Bermer (Lepidoptera: Nymphalidae).
AB  - The nymphalid butterfly Araschnia burejana and the papilionid butterfly Papilio
      xuthus exhibit seasonal diphenism comprising spring-morphs that develop from
      diapause pupae and summer-morphs that develop from non-diapause pupae. The
      development of seasonal morphs in A. burejana is regulated by the timing of
      secretion of ecdysteroids for adult development, whereas that in P. xuthus is
      regulated by the secretion of summer-morph-producing hormone, which is present in
      the brains and is under control of the photoperiod. We investigated whether a
      cerebral factor derived from brains plays a significant role in the regulation of
      seasonal morph development in A. burejana using surgical operations. Pairs of
      chilled diapause pupae that had been chilled for more than 3 months at 4 degrees
      C were joined surgically to each other and then developed into spring-morph or
      spring-like-morph adults. Chilled diapause pupae that were joined with 1-day-old
      non-diapause pupae developed into summer-morph or summer-like-morph adults. When
      the brains of non-diapause pupae were removed surgically 6-8 hr after pupation
      with and without injection of 20-hydroxyecdysone, a large portion of them
      developed into spring-morph or spring-like-morph adults, respectively.
      Furthermore, 90% of non-diapause pupae developed into spring-morph or spring-like
      morph adults when the neck was ligated within 5 min after pupation. These results
      indicated that a cerebral factor showing summer-morph-producing hormone activity,
      which is secreted from the brain in the early pupal stage, in addition to 20
      hydroxyecdysone for adult development, play a significant role in the
      determination of summer-morph development in non-diapause pupae of A. burejana.

PMID- 24668769
TI  - Dietary alpha-mangostin, a xanthone from mangosteen fruit, exacerbates
      experimental colitis and promotes dysbiosis in mice.
AB  - SCOPE: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon.
      alpha-Mangostin (alpha-MG), the most abundant xanthone in mangosteen fruit,
      exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the
      impact of dietary alpha-MG on murine experimental colitis and on the gut
      microbiota of healthy mice. METHODS AND RESULTS: Colitis was induced in C57BL/6J
      mice by administration of dextran sulfate sodium (DSS). Mice were fed control
      diet or diet with alpha-MG (0.1%). alpha-MG exacerbated the pathology of DSS
      induced colitis. Mice fed diet with alpha-MG had greater colonic inflammation and
      injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic
      myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating
      factor, IL-6, and serum amyloid A were also greater in alpha-MG-fed animals than
      in controls. The colonic and cecal microbiota of healthy mice fed alpha-MG but no
      DSS shifted to an increased abundance of Proteobacteria and decreased abundance
      of Firmicutes and Bacteroidetes, a profile similar to that found in human UC.
      CONCLUSION: alpha-MG exacerbated colonic pathology during DSS-induced colitis.
      These effects may be associated with an induction of intestinal dysbiosis by
      alpha-MG. Our results suggest that the use of alpha-MG-containing supplements by
      patients with UC may have unintentional risk.

PMID- 24668771
TI  - Palatal myoclonus: algorithm for management with botulinum toxin based on
      clinical disease characteristics.
AB  - OBJECTIVES/HYPOTHESIS: To review the clinical characteristics and management of
      patients with palatal myoclonus and devise an algorithm for treatment with
      botulinum toxin based on presenting symptoms, clinical examination findings, and
      involved muscle groups. STUDY DESIGN: Retrospective chart review at two clinical
      research centers. METHODS: Between 1985 and 2011, 15 patients with a diagnosis of
      essential palatal myoclonus were assessed. Data were collected on patient
      demographics, disease characteristics, and treatment outcomes. RESULTS: Patients
      were more commonly female (60.0% vs. 40.0%) with average age at onset of 35.6
      years. In 40.0% of patients, the myoclonus began after a viral upper respiratory
      tract infection. Two-thirds of patients had been previously treated
      unsuccessfully with oral medications. Predominant presenting symptoms included
      clicking tinnitus (46.7%), nonaudible awareness of palatal movements +/-
      rhinolalia (20.0%), or both (33.3%). Clinical examination revealed co-incident
      involvement of pharyngeal musculature in 53.3%. Palatal site for initial
      botulinum toxin injection depended on the predominant presenting symptom: for
      tinnitus, 2.5 U were injected transorally into the tensor veli palatini muscle at
      the level of the pterygoid hamulus/lateral soft palate; for palatal movements,
      the injection was placed medially on either side of the uvula. Dose and location
      of subsequent injections were tailored depending on response to the toxin and
      location of subsequent observed maximal muscular contractions. CONCLUSIONS:
      Palatal myoclonus can present with tinnitus or patient-perceived palatal
      movements. Management with botulinum toxin can be tailored to address the muscles
      contributing to the predominant presenting symptoms.

PMID- 24668772
TI  - The innate immune system of the liver: May it explain the stronger viral
      clearance in female sex?

PMID- 24668774
TI  - Conversion of major soy isoflavone glucosides and aglycones in in vitro
      intestinal models.
AB  - SCOPE: This study compares conversion of three major soy isoflavone glucosides
      and their aglycones in a series of in vitro intestinal models. METHODS AND
      RESULTS: In an in vitro human digestion model isoflavone glucosides were not
      deconjugated, whereas studies in a Caco-2 transwell model confirmed that
      deconjugation is essential to facilitate transport across the intestinal barrier.
      Deconjugation was shown upon incubation of the isoflavone glucosides with rat as
      well as human intestinal S9. In incubations with rat intestinal S9 lactase
      phlorizin hydrolase, glucocerebrosidase, and cytosolic broad-specific beta
      glucosidase all contribute significantly to deconjugation, whereas in incubations
      with human intestinal S9 deconjugation appeared to occur mainly through the
      activity of broad-specific beta-glucosidase. Species differences in
      glucuronidation and sulfation were limited and generally within an order of
      magnitude with 7-O-glucuronides being the major metabolites for all three
      isoflavone aglycones and the glucuronidation during first pass metabolism being
      more efficient in rats than in humans. Comparison of the catalytic efficiencies
      reveals that deconjugation is less efficient than conjugation confirming that
      aglycones are unlikely to enter the systemic circulation. CONCLUSION: Altogether,
      the data point at possible differences in the characteristics for intestinal
      conversion of the major soy isoflavones between rat and human, especially with
      respect to their deconjugation.

PMID- 24668773
TI  - Adhiron: a stable and versatile peptide display scaffold for molecular
      recognition applications.
AB  - We have designed a novel non-antibody scaffold protein, termed Adhiron, based on
      a phytocystatin consensus sequence. The Adhiron scaffold shows high thermal
      stability (Tm ca. 101 degrees C), and is expressed well in Escherichia coli. We
      have determined the X-ray crystal structure of the Adhiron scaffold to 1.75 A
      resolution revealing a compact cystatin-like fold. We have constructed a phage
      display library in this scaffold by insertion of two variable peptide regions.
      The library is of high quality and complexity comprising 1.3 * 10(10) clones. To
      demonstrate library efficacy, we screened against the yeast Small Ubiquitin-like
      Modifier (SUMO). In selected clones, variable region 1 often contained sequences
      homologous to the known SUMO interactive motif (V/I-X-V/I-V/I). Four Adhirons
      were further characterised and displayed low nanomolar affinities and high
      specificity for yeast SUMO with essentially no cross-reactivity to human SUMO
      protein isoforms. We have identified binders against >100 target molecules to
      date including as examples, a fibroblast growth factor (FGF1), platelet
      endothelial cell adhesion molecule (PECAM-1; CD31), the SH2 domain Grb2 and a 12
      aa peptide. Adhirons are highly stable and well expressed allowing highly
      specific binding reagents to be selected for use in molecular recognition
      applications. 

PMID- 24668775
TI  - Activation of autophagy and AMPK by gamma-tocotrienol suppresses the adipogenesis
      in human adipose derived stem cells.
AB  - SCOPE: This study investigated the mechanistic details by which gamma-tocotrienol
      (gamma-T3) manipulates adipocyte differentiation in human adipose derived stem
      cells (hASCs). METHODS AND RESULTS: gamma-T3 specifically inhibited the early
      stage of adipocyte differentiation by acting on downstream of C/EBP-beta but
      upstream of C/EBP-alpha in hASCs. In searching a potential mechanism, we
      identified that gamma-T3 promoted two catabolic signaling pathways: (i) AMP
      kinase (AMPK), and (ii) enhanced autophagy, as assessed by autophagic flux and
      cytosolic autophagosome (LC3II) accumulation. In addition, chronic exposure of
      gamma-T3 induced caspase3-mediated apoptotic cell death. The blockage of AMPK by
      a dominant negative mutant of AMPK was insufficient to normalize gamma-T3
      mediated autophagy, suggesting that enhanced autophagic activity of gamma-T3 is
      independent of AMPK activation. Intriguingly, AMPK inhibition significantly
      restored PPAR-gamma activation, but marginally rescued lipid-loaded adipocyte
      morphology due to, at least partly, a lack of lipid droplet-coating protein.
      These data suggest that gamma-T3 activates AMPK and autophagy signaling, which
      synergistically contributes to the suppression of adipogenic conversion of hASCs
      into adipocytes. CONCLUSION: These results provide a novel insight into the
      molecular mechanism involved in anti-adipogenic action of gamma-T3 in humans via
      AMPK and autophagy activation. Thus, gamma-T3 may constitute a new dietary avenue
      to attenuate hyperplastic obesity in humans.

PMID- 24668776
TI  - Engraftment syndrome after allogeneic hematopoietic cell transplantation in
      adults.
AB  - We performed a retrospective study of the engraftment syndrome (ES) as defined by
      the Spitzer Criteria in adult patients undergoing allogeneic hematopoietic cell
      transplantation (HCT) for various hematological malignancies at a single
      institution, over a decade, and analyzed its relationship to acute GVHD; 217
      patients underwent either myeloablative (38.7%) or reduced intensity (61.3%) HCT;
      22.1% met the criteria for ES. Acute GVHD prophylaxis (P = 0.006) and transplants
      prior to 2006 (P < 0.0001) were significantly associated with a risk of ES in
      univariable analysis. Early aGVHD within 4 weeks of engraftment was significantly
      more common in the ES compared to the non ES cohort (21 vs. 8.3% respectively, P
      = 0.02). ES did not predict for future GVHD, as at day +180, the cumulative
      incidences of grades II-IV aGVHD (31 vs. 23%, P = 0.19) and of chronic GVHD at 2
      years of engraftment (42 vs. 36%, P = 0.28) were not significantly different
      between the ES and non ES groups, respectively. No significant differences in
      NRM, overall survival and progression-free survival were observed between the two
      groups. Although predictive of early aGVHD, ES occurred independently of GVHD in
      79% of the patients. Survival outcomes should be evaluated in a larger randomized
      study to investigate if there is a correlation with ES.

PMID- 24668777
TI  - Cervical spine malformation in cornelia de lange syndrome: a report of three
      patients.
AB  - Cornelia de Lange syndrome (CdLS) is a complex genetic disease with skeletal
      involvement mostly related to upper limb malformations. We report on three males
      with clinical and molecular diagnoses of CdLS. Besides typical CdLS features, all
      showed different cervical spine malformations. To the best of our knowledge, this
      is an unusual malformation in the CdLS phenotypic spectrum.

PMID- 24668778
TI  - Authors' reply to Roach.

PMID- 24668779
TI  - Cognitive processes and emotion regulation in depression.
AB  - Sustained negative affect and diminished positive affect are hallmark features of
      Major Depressive Disorder (MDD). Difficulties in emotion regulation have been
      proposed to be at the core of these cardinal symptoms of MDD. It remains unclear,
      however, what underlies emotion regulation difficulties. Cognitive theories of
      depression have focused on cognitive processes and recent studies suggest that
      cognitive biases and deficits in cognitive control may help explain affective
      symptoms of this disorder. Specifically, it is proposed that cognitive biases and
      deficits affect emotion regulation ability thereby setting the stage for
      maintained negative affect and diminished levels of positive affect. The article
      reviews empirical studies that speak to these links and closes with a discussion
      of novel treatment approaches that are inspired by these ideas.

PMID- 24668780
TI  - Glasgow Coma Scores, early opioids, and posttraumatic stress disorder among
      combat amputees.
AB  - A recent study found that combat amputees had a reduced prevalence of
      posttraumatic stress disorder (PTSD) compared with nonamputees with serious
      extremity injuries. We hypothesized that an extended period of impaired
      consciousness or early treatment with morphine could prevent consolidation of
      traumatic memory and the development of PTSD. To examine this hypothesis, we
      retrospectively reviewed 258 combat casualty records from the Iraq or Afghanistan
      conflicts from 2001-2008 in the Expeditionary Medical Encounter Database,
      including medications and Glasgow Coma Scale (GCS) scores recorded at in-theater
      facilities within hours of the index injury. All patients sustained amputations
      from injuries. Psychological diagnoses were extracted from medical records for 24
      months postinjury. None of 20 patients (0%) with GCS scores of 12 or lower had
      PTSD compared to 20% of patients with GCS scores of 12 or greater who did have
      PTSD. For patients with traumatic brain injury, those treated with intravenous
      morphine within hours of injury had a significantly lower prevalence of PTSD
      (6.3%) and mood disorders (15.6%) compared to patients treated with fentanyl only
      (prevalence of PTSD = 41.2%, prevalence of mood disorder = 47.1%). GCS scores and
      morphine and fentanyl treatments were not significantly associated with
      adjustment, anxiety, or substance abuse disorders. 

PMID- 24668781
TI  - Rate coefficients of C(1) and C(2) Criegee intermediate reactions with formic and
      acetic Acid near the collision limit: direct kinetics measurements and
      atmospheric implications.
AB  - Rate coefficients are directly determined for the reactions of the Criegee
      intermediates (CI) CH2 OO and CH3 CHOO with the two simplest carboxylic acids,
      formic acid (HCOOH) and acetic acid (CH3 COOH), employing two complementary
      techniques: multiplexed photoionization mass spectrometry and cavity-enhanced
      broadband ultraviolet absorption spectroscopy. The measured rate coefficients are
      in excess of 1*10(-10)  cm(3)  s(-1) , several orders of magnitude larger than
      those suggested from many previous alkene ozonolysis experiments and assumed in
      atmospheric modeling studies. These results suggest that the reaction with
      carboxylic acids is a substantially more important loss process for CIs than is
      presently assumed. Implementing these rate coefficients in global atmospheric
      models shows that reactions between CI and organic acids make a substantial
      contribution to removal of these acids in terrestrial equatorial areas and in
      other regions where high CI concentrations occur such as high northern latitudes,
      and implies that sources of acids in these areas are larger than previously
      recognized. 

PMID- 24668782
TI  - Clinical, electrophysiological, and molecular findings in early onset hereditary
      neuropathy with liability to pressure palsy.
AB  - INTRODUCTION: The first episode of hereditary neuropathy with liability to
      pressure palsy (HNPP) in childhood is rare. METHODS: We analyzed retrospectively
      the data of 7 patients with a deletion in PMP22 and onset of symptoms before age
      18 years. Direct sequencing of the LITAF (lipopolysaccharide-induced tumor
      necrosis factor) gene was performed in patients and family members. RESULTS:
      Clinical presentations varied from mononeuropathies to brachial plexopathy, with
      recurrent episodes in 4 patients. Electrophysiological abnormalities
      characteristic for HNNP were found in most subjects. Analysis of the LITAF gene
      revealed an Ile92Val polymorphism in 6 of 7 (86%) probands and 5 of 7 (83%)
      family members, over 4 times greater frequency than in the general population.
      CONCLUSIONS: Clinical suspicion of HNPP even when nerve conduction study results
      do not fulfill HNPP criteria should indicate genetic testing. In our patients,
      early-onset HNPP was associated frequently with isoleucine92valine LITAF
      polymorphism.

PMID- 24668783
TI  - Three-dimensional spatial configuration of tumour cells confers resistance to
      chemotherapy independent of drug delivery.
AB  - Anticancer drug discovery has been hampered by the lack of reliable preclinical
      models, which routinely use cells grown in two-dimensional (2D) culture systems.
      However, many of the characteristics of cells in 2D culture do not translate into
      the findings in animal xenografts. Three-dimensional (3D) growth may be
      responsible for some of these changes, and models using cells grown in 3D may
      form a more representative step in tumouricidal validation prior to animal
      implantation and human testing. For the 3D model, we cultured 143.98.2, SaOS2 or
      U2OS osteosarcoma cells seeded in porous Bombyx mori silk sponges. We conducted
      real-time PCR on cells grown in 2D culture and 3D scaffolds for the proliferation
      markers cyclin B1 and E2F1 and the actin regulator RhoA, and found a significant
      decrease in expression levels for the 3D tumour models (p = 0.02, < 0.001 and
      0.008 for cyclin B1, E2F1 and RhoA for 143.98.2; p = 0.02, 0.002 and 0.02 for
      cyclin B1, E2F1 and RhoA for U2OS, respectively). In contrast, p21 was
      upregulated when SaOS2 and U2OS were cultured in the 3D scaffolds (p < 0.001) and
      there was no increase in DNA quantity during the culture period. We
      correspondingly observed G1 arrest when cell cycle analysis was conducted.
      Cytotoxicity results for cells treated with serial dilutions of doxorubicin and
      cisplatin showed that cells in 3D scaffolds were less sensitive to drug treatment
      than in 2D culture, and the difference was more pronounced for cell cycle
      specific agents. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668788
TI  - Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet
      induced obesity and insulin resistance in mice.
AB  - SCOPE: Mast cells play important roles in diet-induced obesity and diabetes, and
      some synthetic mast cell stabilizers can improve related metabolic disturbances
      in mice. Luteolin (LU) is a potent natural mast cell stabilizer. However, a
      direct correlation between LU and these common metabolic diseases is not
      established. METHODS AND RESULTS: Male C57BL/6 mice were fed low-fat diet, high
      fat diet (HFD), HFD with 0.002 and 0.01% LU for 12 wk, respectively. Dietary LU
      suppressed HFD-induced body weight gain, fat deposition, and adipocyte
      hypertrophy. Meanwhile, glucose intolerance and insulin sensitivity was also
      improved. Interestingly, dietary LU ameliorated angiogenesis and associated cell
      apoptosis and cathepsin activity in epididymis adipose tissues, which is a
      critical mechanism that mast cells are involved in diet-induced obesity and
      diabetes. Further, we showed dietary LU reduced mast cell and macrophage
      infiltrations and inflammatory cytokine levels in epididymis adipose tissues.
      Finally, LU inhibited mast cell-derived IL-6 expression, which is a key cytokine
      that contributes to mast cell-associated metabolic derangements, and protein
      kinase C activator phorbol myristoyl acetate reversed the inhibitory effects.
      CONCLUSIONS: As a natural flavonoid, low-dose diet supplement of LU ameliorates
      diet-induced obesity and insulin resistance in mice, suggesting a new therapeutic
      and interventional approach for these diseases.

PMID- 24668789
TI  - Ending vertical transmission of hepatitis B: the third trimester intervention.

PMID- 24668790
TI  - Association between relative systemic hypertension and otologic disorders in
      patients with sickle cell-hemoglobin C disorder.

PMID- 24668791
TI  - Selenoquinones stabilized by ruthenium(II) arene complexes: synthesis, structure,
      and cytotoxicity.
AB  - A new series of monoselenoquinone and diselenoquinone pi complexes, [(eta(6) -p
      cymene)Ru(eta(4) -C6 R4 SeE)] (R=H, E=Se (6); R=CH3 , E=Se (7); R=H, E=O (8)), as
      well as selenolate pi complexes [(eta(6) -p-cymene)Ru(eta(5) -C6 H3 R2 Se)][SbF6
      ] (R=H (9); R=CH3 (10)), stabilized by arene ruthenium moieties were prepared in
      good yields through nucleophilic substitution reactions from dichlorinated-arene
      and hydroxymonochlorinated-arene ruthenium complexes [(eta(6) -p-cymene)Ru(C6 R4
      XCl)][SbF6 ]2 (R=H, X=Cl (1); R=CH3 , X=Cl (2); R=H, X=OH (3)) as well as the
      monochlorinated pi complexes [(eta(6) -p-cymene)Ru(eta(5) -C6 H3 R2 Cl)][SbF6 ]2
      (R=H (4); R=CH3 (5)). The X-ray crystallographic structures of two of the
      compounds, [(eta(6) -p-cymene)Ru(eta(4) -C6 Me4 Se2 )] (7) and [(eta(6) -p
      cymene)Ru(eta(4) -C6 H4 SeO)] (8), were determined. The structures confirm the
      identity of the target compounds and ascertain the coordination mode of these
      unprecedented ruthenium pi complexes of selenoquinones. Furthermore, these new
      compounds display relevant cytotoxic properties towards human ovarian cancer
      cells. 

PMID- 24668792
TI  - Under-expression of annexin A2 is associated with Kazakh's esophageal squamous
      cell carcinoma.
AB  - The aim of the study was to identify candidate biomarkers for esophageal squamous
      cell carcinoma (ESCC) in Kazakh ethnic in Xinjiang as well as to reveal the
      potential role of Annexin A2 in ESCC carcinogenesis and progression. Five paired
      of Kazakh's ESCC tissues (T) and matched adjacent morphologically normal tissues
      (N) were separated by two-dimensional electrophoresis (2-DE) and differential
      proteins were identified by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS). Annexin A2 was identified as a down
      regulated protein in Kazakh's ESCC and further validated by immunohistochemistry
      (IHC) in 77 Kazakh's ESCC formalin-fixed paraffin-embeded (FFPE) samples. The
      expression level of Annexin A2 protein significantly correlated with the degree
      of ESCC differentiation and depth of invasion. For clarification of the role of
      Annexin A2 in regulating cell phenotype, in vitro eukaryotic expression vectors
      harboring full length Annexin A2 (pCMV-XL5-Annexin A2) was tranfected into Eca109
      cells, and transfection effects were evaluated by RT-PCR and Western blotting
      analysis, respectively. Functionally, there was a significant decrease in cell
      proliferation, migration, and invasion capability in Eca109 with transfected pCMV
      XL5-Annexin A2 compared to the controls. Furthermore, up-regulating Annexin A2
      can significantly cause cell cycle arrest at the G2 phase, but no apoptosis was
      induced. Together, our findings suggested that Annexin A2 was involved in
      malignant phenotype and was a potential biomark for molecular classification in
      ESCC.

PMID- 24668794
TI  - Establishment and characterization of the Masquelet induced membrane technique in
      a rat femur critical-sized defect model.
AB  - The Masquelet induced membrane technique for reconstructing large diaphyseal
      defects has been shown to be a promising clinical treatment, yet relatively
      little is known about the cellular, histological and biochemical make-up of these
      membranes and how they produce this positive clinical outcome. We compared
      cellular make-up, histological changes and growth factor expression in membranes
      induced around femur bone defects and in subcutaneous pockets at 2, 4 and 6 weeks
      after induction, and to the periosteum. We found that membranes formed around
      bone defects were similar to those formed in subcutaneous pockets; however, both
      were significantly different from periosteum with regard to structural
      characteristics, location of blood vessels and overall thickness. Membranes
      induced at the femur defect (at 2 weeks) and in periosteum contain mesenchymal
      stem cells (MSCs; STRO-1+ ) which were not found in membranes induced
      subcutaneously. BMP-2, TGFbeta and VEGF were significantly elevated in membranes
      induced around femur defects in comparison to subcutaneously induced membranes,
      whereas SDF-1 was not detectable in membranes induced at either site. We found
      that osteogenic and neovascular activity had mostly subsided by 6 weeks in
      membranes formed at both sites. It was conclude that cellular composition and
      growth factor content in induced membranes depends on the location where the
      membrane is induced and differs from periosteum. Osteogenic and neovascular
      activity in the membranes is maximal between 2 and 4 weeks and subsides after 6.
      Based on this, better and quicker bone healing might be achieved if the PMMA
      cement were replaced with a bone graft earlier in the Masquelet technique.
      Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668795
TI  - Lymphedema in tuberous sclerosis complex.
AB  - Congenital lymphedema has been described as a possible rare association of
      tuberous sclerosis complex (TSC), with only six previous cases reported in the
      literature. TSC is an autosomal dominant, multisystem disorder connected to
      aberrant regulation of the mammalian target of rapamycin (mTOR) pathway. The aim
      of this study is to review cases of lymphedema in a large cohort of TSC patients.
      The medical records of 268 patients seen at The Herscot Center for Children and
      Adults with Tuberous Sclerosis Complex at the Massachusetts General Hospital from
      2002 to 2012 were retrospectively reviewed for reports of lymphedema or edema of
      unknown etiology. Genotypic and phenotypic data were collected in accordance with
      institutional review board (IRB) approval. This cohort presents two new cases of
      congenital lymphedema in TSC patients and acquired lymphedema was found in eight
      additional cases. Thus, we report 10 new cases of lymphedema in TSC (4%). The two
      patients with congenital lymphedema were female, as were the previous six
      reported cases. The frequency of lymphedema reported here (4%) is higher than the
      estimated prevalence in the general population (0.133-0.144%), suggesting a
      higher frequency of lymphedema in TSC. This study shows that patients with TSC
      and lymphedema are more likely to be females with renal AMLs and suggests that
      congenital lymphedema is a gender-specific (female) manifestation of TSC.
      Exploration of the potential role of mTOR antagonists may be important in
      treatment of lymphedema in TSC patients.

PMID- 24668796
TI  - Radical prostatectomy v radiation: only a randomised trial can provide the
      answer.

PMID- 24668797
TI  - Etiologies and diagnostic work-up of extreme macrocytosis defined by an
      erythrocyte mean corpuscular volume over 130 degrees fL: A study of 109 patients.

PMID- 24668798
TI  - Postprandial triglyceride-rich lipoproteins promote invasion of human coronary
      artery smooth muscle cells in a fatty-acid manner through PI3k-Rac1-JNK
      signaling.
AB  - SCOPE: The aim was to investigate the effect of postprandial triglyceride-rich
      lipoproteins (TRLs) with different fatty acid compositions on human coronary
      artery smooth muscle cell (hCASMC) invasion and to identify the molecular
      pathways involved. METHODS AND RESULTS: TRLs were isolated from the plasma of
      healthy volunteers after the ingestion of single meals enriched in MUFAs,
      saturated fatty acids (SFAs), or PUFAs. hCASMC invasion was analyzed using
      transwell chambers with Matrigel. TRLs-SFAs provoked the highest invasion,
      followed by TRLs-MUFAs and TRLs-PUFAs. Inhibition studies with Orlistat showed
      that invasion was dependent on the fatty acid composition of the TRLs. Fatty
      acids incorporated into the cell membranes strongly associated with cell
      invasion. Pull-down assays showed that TRLs-SFAs were able to increase Rac1
      activity via inhibition of RhoA-dependent signaling. Chemical inhibition and
      siRNA studies showed that Rac1, PI3k, JNK, and MMP2 regulates TRL-SFA-induced
      hCASMC invasion. CONCLUSION: We demonstrate for the first time that TRLs induce
      hCASMCs invasion in a fatty acid dependent manner. This effect in TRLs-SFAs is
      mediated by the PI3k-Rac1-JNK, RhoA, and Rac1-MMP2 pathways. The ingestion of
      MUFA, compared to other dietary fatty acids such as SFA, could be considered as a
      nutritional strategy to reduce the atherosclerotic plaque formation.

PMID- 24668800
TI  - Role of platelets in systemic tissue protection after remote ischemic
      preconditioning.

PMID- 24668799
TI  - Fatty acid synthase is required for mammary gland development and milk production
      during lactation.
AB  - The mammary gland is one of the few adult tissues that strongly induce de novo
      fatty acid synthesis upon physiological stimulation, suggesting that fatty acid
      is important for milk production during lactation. The committed enzyme to
      perform this function is fatty acid synthase (FASN). To determine whether de novo
      fatty acid synthesis is obligatory or dietary fat is sufficient for mammary gland
      development and function during lactation, Fasn was specifically knocked out in
      mouse mammary epithelial cells. We found that deletion of Fasn hindered the
      development and induced the premature involution of the lactating mammary gland
      and significantly decreased medium- and long-chain fatty acids and total fatty
      acid contents in the milk. Consequently, pups nursing from Fasn knockout mothers
      experienced growth retardation and preweanling death, which was rescued by cross
      fostering pups to a lactating wild-type mother. These results demonstrate that
      FASN is essential for the development, functional competence, and maintenance of
      the lactating mammary gland. 

PMID- 24668801
TI  - Efficient luminescence from fluorene- and spirobifluorene-based lanthanide
      complexes upon near-visible irradiation.
AB  - We describe herein the synthesis and photophysical characterization of new
      lanthanide complexes that consist of a (9,9-dimethylfluoren-2-yl)-2-oxoethyl or a
      (9,9'-spirobifluoren-2-yl)-2-oxoethyl unit as the antenna, covalently linked to a
      1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) unit as the Ln(3+)
      (Gd(3+), Eu(3+), Sm(3+), Tb(3+), Dy(3+)) coordination site. We were able to
      translate the spectroscopic properties of the innovative bipartite ligands into
      the formation of highly luminescent europium complexes that exhibit efficient
      emission (phi(se)>0.1) upon sensitization in the near-visible region, that is,
      with an excitation wavelength above 350 nm. The luminescence of the Eu(3+)
      complexes is clearly detectable at concentrations as low as 10 pM. Furthermore,
      the structural organization of these bipartite ligands makes the complexes highly
      soluble in aqueous solutions and chemically stable over time.

PMID- 24668802
TI  - Climate variability and vulnerability to climate change: a review.
AB  - The focus of the great majority of climate change impact studies is on changes in
      mean climate. In terms of climate model output, these changes are more robust
      than changes in climate variability. By concentrating on changes in climate
      means, the full impacts of climate change on biological and human systems are
      probably being seriously underestimated. Here, we briefly review the possible
      impacts of changes in climate variability and the frequency of extreme events on
      biological and food systems, with a focus on the developing world. We present new
      analysis that tentatively links increases in climate variability with increasing
      food insecurity in the future. We consider the ways in which people deal with
      climate variability and extremes and how they may adapt in the future. Key
      knowledge and data gaps are highlighted. These include the timing and
      interactions of different climatic stresses on plant growth and development,
      particularly at higher temperatures, and the impacts on crops, livestock and
      farming systems of changes in climate variability and extreme events on pest-weed
      disease complexes. We highlight the need to reframe research questions in such a
      way that they can provide decision makers throughout the food system with
      actionable answers, and the need for investment in climate and environmental
      monitoring. Improved understanding of the full range of impacts of climate change
      on biological and food systems is a critical step in being able to address
      effectively the effects of climate variability and extreme events on human
      vulnerability and food security, particularly in agriculturally based developing
      countries facing the challenge of having to feed rapidly growing populations in
      the coming decades. 

PMID- 24668803
TI  - A microRNA processing defect in smokers' macrophages is linked to SUMOylation of
      the endonuclease DICER.
AB  - Despite the fact that alveolar macrophages play an important role in smoking
      related disease, little is known about what regulates their pathophysiologic
      phenotype. Evaluating smoker macrophages, we found significant down-regulation of
      multiple microRNAs (miRNAs). This work investigates the hypothesis that cigarette
      smoke alters mature miRNA expression in lung macrophages by inhibiting processing
      of primary miRNA transcripts. Studies on smoker alveolar macrophages showed a
      defect in miRNA maturation. Studies on the miRNA biogenesis machinery led us to
      focus on the cytosolic RNA endonuclease, DICER. DICER cleaves the stem-loop
      structure from pre-miRNAs, allowing them to dissociate into their mature 20-22
      nucleotide single-stranded form. DICER activity assays confirmed impaired DICER
      activity following cigarette smoke exposure. Further protein studies demonstrated
      a decreased expression of the native 217-kDa form of DICER and an accumulation of
      high molecular weight forms with cigarette smoke exposure. This molecular mass
      shift was shown to contain SUMO moieties and could be blocked by silencing RNA
      directed at the primary SUMOylating ligase, Ubc9. In determining the cigarette
      smoke components responsible for changes in DICER, we found that N
      acetylcysteine, an antioxidant and anti-aldehyde, protected DICER protein and
      activity from cigarette smoke extract. This massive down-regulation of miRNAs
      (driven in part by alterations in DICER) may be an important regulator of the
      disease-promoting macrophage phenotype found in the lungs of smokers. 

PMID- 24668804
TI  - Biochemical, cellular, and biophysical characterization of a potent inhibitor of
      mutant isocitrate dehydrogenase IDH1.
AB  - Two mutant forms (R132H and R132C) of isocitrate dehydrogenase 1 (IDH1) have been
      associated with a number of cancers including glioblastoma and acute myeloid
      leukemia. These mutations confer a neomorphic activity of 2-hydroxyglutarate (2
      HG) production, and 2-HG has previously been implicated as an oncometabolite.
      Inhibitors of mutant IDH1 can potentially be used to treat these diseases. In
      this study, we investigated the mechanism of action of a newly discovered
      inhibitor, ML309, using biochemical, cellular, and biophysical approaches.
      Substrate binding and product inhibition studies helped to further elucidate the
      IDH1 R132H catalytic cycle. This rapidly equilibrating inhibitor is active in
      both biochemical and cellular assays. The (+) isomer is active (IC50 = 68 nm),
      whereas the (-) isomer is over 400-fold less active (IC50 = 29 MUm) for IDH1
      R132H inhibition. IDH1 R132C was similarly inhibited by (+)-ML309. WT IDH1 was
      largely unaffected by (+)-ML309 (IC50 >36 MUm). Kinetic analyses combined with
      microscale thermophoresis and surface plasmon resonance indicate that this
      reversible inhibitor binds to IDH1 R132H competitively with respect to alpha
      ketoglutarate and uncompetitively with respect to NADPH. A reaction scheme for
      IDH1 R132H inhibition by ML309 is proposed in which ML309 binds to IDH1 R132H
      after formation of the IDH1 R132H NADPH complex. ML309 was also able to inhibit 2
      HG production in a glioblastoma cell line (IC50 = 250 nm) and had minimal
      cytotoxicity. In the presence of racemic ML309, 2-HG levels drop rapidly. This
      drop was sustained until 48 h, at which point the compound was washed out and 2
      HG levels recovered. 

PMID- 24668805
TI  - Ischemia-like oxygen and glucose deprivation mediates down-regulation of cell
      surface gamma-aminobutyric acidB receptors via the endoplasmic reticulum (ER)
      stress-induced transcription factor CCAAT/enhancer-binding protein (C/EBP)
      homologous protein (CHOP).
AB  - Cerebral ischemia frequently leads to long-term disability and death.
      Excitotoxicity is believed to be the main cause for ischemia-induced neuronal
      death. Although a role of glutamate receptors in this process has been firmly
      established, the contribution of metabotropic GABAB receptors, which control
      excitatory neurotransmission, is less clear. A prominent characteristic of
      ischemic insults is endoplasmic reticulum (ER) stress associated with the up
      regulation of the transcription factor CCAAT/enhancer-binding protein-homologous
      protein (CHOP). After inducing ER stress in cultured cortical neurons by
      sustained Ca(2+) release from intracellular stores or by a brief episode of
      oxygen and glucose deprivation (in vitro model of cerebral ischemia), we observed
      an increased expression of CHOP accompanied by a strong reduction of cell surface
      GABAB receptors. Our results indicate that down-regulation of cell surface GABAB
      receptors is caused by the interaction of the receptors with CHOP in the ER.
      Binding of CHOP prevented heterodimerization of the receptor subunits GABAB1 and
      GABAB2 and subsequent forward trafficking of the receptors to the cell surface.
      The reduced level of cell surface receptors diminished GABAB receptor signaling
      and, thus, neuronal inhibition. These findings indicate that ischemia-mediated up
      regulation of CHOP down-regulates cell surface GABAB receptors by preventing
      their trafficking from the ER to the plasma membrane. This mechanism leads to
      diminished neuronal inhibition and may contribute to excitotoxicity in cerebral
      ischemia. 

PMID- 24668807
TI  - The human enzyme that converts dietary provitamin A carotenoids to vitamin A is a
      dioxygenase.
AB  - beta-Carotene 15-15'-oxygenase (BCO1) catalyzes the oxidative cleavage of dietary
      provitamin A carotenoids to retinal (vitamin A aldehyde). Aldehydes readily
      exchange their carbonyl oxygen with water, making oxygen labeling experiments
      challenging. BCO1 has been thought to be a monooxygenase, incorporating oxygen
      from O2 and H2O into its cleavage products. This was based on a study that used
      conditions that favored oxygen exchange with water. We incubated purified
      recombinant human BCO1 and beta-carotene in either (16)O2-H2(18)O or (18)O2
      H2(16)O medium for 15 min at 37  degrees C, and the relative amounts of (18)O
      retinal and (16)O-retinal were measured by liquid chromatography-tandem mass
      spectrometry. At least 79% of the retinal produced by the reaction has the same
      oxygen isotope as the O2 gas used. Together with the data from (18)O-retinal
      H2(16)O and (16)O-retinal-H2(18)O incubations to account for nonenzymatic oxygen
      exchange, our results show that BCO1 incorporates only oxygen from O2 into
      retinal. Thus, BCO1 is a dioxygenase. 

PMID- 24668806
TI  - Fragments of bacterial endoglycosidase s and immunoglobulin g reveal subdomains
      of each that contribute to deglycosylation.
AB  - Endoglycosidase S (EndoS) is a glycoside-hydrolase secreted by the bacterium
      Streptococcus pyogenes. EndoS preferentially hydrolyzes the N-linked glycans from
      the Fc region of IgG during infection. This hydrolysis impedes Fc functionality
      and contributes to the immune evasion strategy of S. pyogenes. Here, we
      investigate the mechanism of human serum IgG deactivation by EndoS. We expressed
      fragments of IgG1 and demonstrated that EndoS was catalytically active against
      all of them including the isolated CH2 domain of the Fc domain. Similarly, we
      sought to investigate which domains within EndoS could contribute to activity.
      Bioinformatics analysis of the domain organization of EndoS confirmed the
      previous predictions of a chitinase domain and leucine-rich repeat but also
      revealed a putative carbohydrate binding module (CBM) followed by a C-terminal
      region. Using expressed fragments of EndoS, circular dichroism of the isolated
      CBM, and a CBM-C-terminal region fusion revealed folded domains dominated by beta
      sheet and alpha helical structure, respectively. Nuclear magnetic resonance
      analysis of the CBM with monosaccharides was suggestive of carbohydrate binding
      functionality. Functional analysis of truncations of EndoS revealed that, whereas
      the C-terminal of EndoS is dispensable for activity, its deletion impedes the
      hydrolysis of IgG glycans. 

PMID- 24668808
TI  - Reaction mechanism of the bicopper enzyme peptidylglycine alpha-hydroxylating
      monooxygenase.
AB  - Peptidylglycine alpha-hydroxylating monooxygenase is a noninteracting bicopper
      enzyme that stereospecifically hydroxylates the terminal glycine of small
      peptides for its later amidation. Neuroendocrine messengers, such as oxytocin,
      rely on the biological activity of this enzyme. Each catalytic turnover requires
      one oxygen molecule, two protons from the solvent, and two electrons. Despite
      this enzyme having been widely studied, a consensus on the reaction mechanism has
      not yet been found. Experiments and theoretical studies favor a pro-S abstraction
      of a hydrogen atom followed by the rebinding of an OH group. However, several
      hydrogen-abstracting species have been postulated; because two protons are
      consumed during the reaction, several protonation states are available. An
      electron transfer between the copper atoms could play a crucial role for the
      catalysis as well. This leads to six possible abstracting species. In this study,
      we compare them on equal footing. We perform quantum mechanics/molecular
      mechanics calculations, considering the glycine hydrogen abstraction. Our results
      suggest that the most likely mechanism is a protonation of the abstracting
      species before the hydrogen abstraction and another protonation as well as a
      reduction before OH rebinding. 

PMID- 24668809
TI  - The S229L colon tumor-associated variant of DNA polymerase beta induces cellular
      transformation as a result of decreased polymerization efficiency.
AB  - DNA polymerase beta (Pol beta) plays a key role in base excision repair (BER) by
      filling in small gaps that are generated after base adducts are excised from the
      DNA. Pol beta is mutated in a large number of colorectal tumors, and these
      mutations may drive carcinogenesis. In the present study, we wished to determine
      whether the S229L somatic Pol beta variant identified in a stage 3 colorectal
      tumor is a driver of carcinogenesis. We show that S229L does not possess any
      defects in binding to either DNA or nucleotides compared with the WT enzyme, but
      exhibits a significant loss of polymerization efficiency, largely due to an 8
      fold decrease in the polymerization rate. S229L participates in BER, but due to
      its lower catalytic rate, does so more slowly than WT. Expression of S229L in
      mammalian cells induces the accumulation of BER intermediate substrates,
      chromosomal aberrations, and cellular transformation. Our results are consistent
      with the interpretation that S229L is a driver of carcinogenesis, likely as a
      consequence of its slow polymerization activity during BER in vivo. 

PMID- 24668810
TI  - Locus of enterocyte effacement-encoded regulator (Ler) of pathogenic Escherichia
      coli competes off histone-like nucleoid-structuring protein (H-NS) through
      noncooperative DNA binding.
AB  - The locus of enterocyte effacement-encoded regulator (Ler) of enteropathogenic
      and enterohemorrhagic Escherichia coli (EPEC and EHEC) functions to activate
      transcription of virulence genes silenced by the histone-like nucleoid
      structuring protein (H-NS). Despite its important role in the bacterial gene
      regulation, the binding mode of Ler to DNA and its mechanism in alleviating genes
      repressed by H-NS are largely unknown. In this study, we use magnetic tweezers to
      demonstrate that Ler binds extended DNA through a largely noncooperative process,
      which results in DNA stiffening and DNA folding depending on protein
      concentration. We also show that Ler can replace prebound H-NS on DNA over a
      range of potassium and magnesium concentrations. Our findings reveal the DNA
      binding properties of Ler and shed light to further understand the anti-silencing
      activity of Ler. 

PMID- 24668811
TI  - Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP)
      mutations in the actin-binding domain cause disruption of skeletal muscle actin
      filaments in myofibrillar myopathy.
AB  - The core of skeletal muscle Z-discs consists of actin filaments from adjacent
      sarcomeres that are cross-linked by alpha-actinin homodimers. Z-disc-associated,
      alternatively spliced, PDZ motif-containing protein (ZASP)/Cypher interacts with
      alpha-actinin, myotilin, and other Z-disc proteins via the PDZ domain. However,
      these interactions are not sufficient to maintain the Z-disc structure. We show
      that ZASP directly interacts with skeletal actin filaments. The actin-binding
      domain is between the modular PDZ and LIM domains. This ZASP region is
      alternatively spliced so that each isoform has unique actin-binding domains. All
      ZASP isoforms contain the exon 6-encoded ZASP-like motif that is mutated in
      zaspopathy, a myofibrillar myopathy (MFM), whereas the exon 8-11 junction-encoded
      peptide is exclusive to the postnatal long ZASP isoform (ZASP-LDeltaex10). MFM is
      characterized by disruption of skeletal muscle Z-discs and accumulation of
      myofibrillar degradation products. Wild-type and mutant ZASP interact with alpha
      actin, alpha-actinin, and myotilin. Expression of mutant, but not wild-type, ZASP
      leads to Z-disc disruption and F-actin accumulation in mouse skeletal muscle, as
      in MFM. Mutations in the actin-binding domain of ZASP-LDeltaex10, but not other
      isoforms, cause disruption of the actin cytoskeleton in muscle cells. These
      isoform-specific mutation effects highlight the essential role of the ZASP
      LDeltaex10 isoform in F-actin organization. Our results show that MFM-associated
      ZASP mutations in the actin-binding domain have deleterious effects on the core
      structure of the Z-discs in skeletal muscle. 

PMID- 24668812
TI  - Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter
      NCC and subsequent clathrin-mediated endocytosis.
AB  - The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl
      transport protein in the distal convoluted tubule (DCT). The transport activity
      of NCC can be regulated by phosphorylation, but knowledge of modulation of NCC
      trafficking by phosphorylation is limited. In this study, we generated novel
      tetracycline-inducible Madin-Darby canine kidney type I (MDCKI) cell lines
      expressing NCC to examine the role of NCC phosphorylation and ubiquitylation on
      NCC endocytosis. In MDCKI-NCC cells, NCC was highly glycosylated at molecular
      weights consistent with NCC monomers and dimers. NCC constitutively cycles to the
      apical plasma membrane of MDCKI-NCC cells, with 20-30% of the membrane pool of
      NCC internalized within 30 min. The use of dynasore, PitStop2, methyl-beta
      cyclodextrin, nystatin, and filipin (specific inhibitors of either clathrin
      dependent or -independent endocytosis) demonstrated that NCC is internalized via
      a clathrin-mediated pathway. Reduction of endocytosis resulted in greater levels
      of NCC in the plasma membrane. Immunogold electron microscopy confirmed the
      association of NCC with the clathrin-mediated internalization pathway in rat DCT
      cells. Compared with controls, inducing phosphorylation of NCC via low chloride
      treatment or mimicking phosphorylation by replacing Thr-53, Thr-58, and Ser-71
      residues with Asp resulted in increased membrane abundance and reduced rates of
      NCC internalization. NCC ubiquitylation was lowest in the conditions with
      greatest NCC phosphorylation, thus providing a mechanism for the reduced
      endocytosis. In conclusion, our data support a model where NCC is constitutively
      cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to
      both increase NCC activity and decrease NCC endocytosis, together increasing NaCl
      transport in the DCT. 

PMID- 24668813
TI  - Nucleotide interactions of the human voltage-dependent anion channel.
AB  - The voltage-dependent anion channel (VDAC) mediates and gates the flux of
      metabolites and ions across the outer mitochondrial membrane and is a key player
      in cellular metabolism and apoptosis. Here we characterized the binding of
      nucleotides to human VDAC1 (hVDAC1) on a single-residue level using NMR
      spectroscopy and site-directed mutagenesis. We find that hVDAC1 possesses one
      major binding region for ATP, UTP, and GTP that partially overlaps with a
      previously determined NADH binding site. This nucleotide binding region is formed
      by the N-terminal alpha-helix, the linker connecting the helix to the first beta
      strand and adjacent barrel residues. hVDAC1 preferentially binds the charged
      forms of ATP, providing support for a mechanism of metabolite transport in which
      direct binding to the charged form exerts selectivity while at the same time
      permeation of the Mg(2+)-complexed ATP form is possible. 

PMID- 24668814
TI  - Protrudin regulates endoplasmic reticulum morphology and function associated with
      the pathogenesis of hereditary spastic paraplegia.
AB  - Protrudin is a membrane protein that regulates polarized vesicular trafficking in
      neurons. The protrudin gene (ZFYVE27) is mutated in a subset of individuals with
      hereditary spastic paraplegia (HSP), and protrudin is therefore also referred to
      as spastic paraplegia (SPG) 33. We have now generated mice that express a
      transgene for dual epitope-tagged protrudin under control of a neuron-specific
      promoter, and we have subjected highly purified protrudin-containing complexes
      isolated from the brain of these mice to proteomics analysis to identify proteins
      that associate with protrudin. Protrudin was found to interact with other HSP
      related proteins including myelin proteolipid protein 1 (SPG2), atlastin-1
      (SPG3A), REEP1 (SPG31), REEP5 (similar to REEP1), Kif5A (SPG10), Kif5B, Kif5C,
      and reticulon 1, 3, and 4 (similar to reticulon 2, SPG12). Membrane topology
      analysis indicated that one of three hydrophobic segments of protrudin forms a
      hydrophobic hairpin domain similar to those of other SPG proteins. Protrudin was
      found to localize predominantly to the tubular endoplasmic reticulum (ER), and
      forced expression of protrudin promoted the formation and stabilization of the
      tubular ER network. The protrudin(G191V) mutant, which has been identified in a
      subset of HSP patients, manifested an increased intracellular stability, and
      cells expressing this mutant showed an increased susceptibility to ER stress. Our
      results thus suggest that protrudin contributes to the regulation of ER
      morphology and function, and that its deregulation by mutation is a causative
      defect in HSP. 

PMID- 24668815
TI  - Divergent transducer-specific molecular efficacies generate biased agonism at a G
      protein-coupled receptor (GPCR).
AB  - The concept of "biased agonism" arises from the recognition that the ability of
      an agonist to induce a receptor-mediated response (i.e. "efficacy") can differ
      across the multiple signal transduction pathways (e.g. G protein and beta
      arrestin (betaarr)) emanating from a single GPCR. Despite the therapeutic promise
      of biased agonism, the molecular mechanism(s) whereby biased agonists selectively
      engage signaling pathways remain elusive. This is due in large part to the
      challenges associated with quantifying ligand efficacy in cells. To address this,
      we developed a cell-free approach to directly quantify the transducer-specific
      molecular efficacies of balanced and biased ligands for the angiotensin II type 1
      receptor (AT1R), a prototypic GPCR. Specifically, we defined efficacy in
      allosteric terms, equating shifts in ligand affinity (i.e. KLo/KHi) at AT1R-Gq
      and AT1R-betaarr2 fusion proteins with their respective molecular efficacies for
      activating Gq and betaarr2. Consistent with ternary complex model predictions,
      transducer-specific molecular efficacies were strongly correlated with cellular
      efficacies for activating Gq and betaarr2. Subsequent comparisons across
      transducers revealed that biased AT1R agonists possess biased molecular
      efficacies that were in strong agreement with the signaling bias observed in
      cellular assays. These findings not only represent the first measurements of the
      thermodynamic driving forces underlying differences in ligand efficacy between
      transducers but also support a molecular mechanism whereby divergent transducer
      specific molecular efficacies generate biased agonism at a GPCR. 

PMID- 24668816
TI  - Structure of a conserved Golgi complex-targeting signal in coronavirus envelope
      proteins.
AB  - Coronavirus envelope (CoV E) proteins are ~100-residue polypeptides with at least
      one channel-forming alpha-helical transmembrane (TM) domain. The extramembrane C
      terminal tail contains a completely conserved proline, at the center of a
      predicted beta-coil-beta motif. This hydrophobic motif has been reported to
      constitute a Golgi-targeting signal or a second TM domain. However, no structural
      data for this or other extramembrane domains in CoV E proteins is available.
      Herein, we show that the E protein in the severe acute respiratory syndrome virus
      has only one TM domain in micelles, whereas the predicted beta-coil-beta motif
      forms a short membrane-bound alpha-helix connected by a disordered loop to the TM
      domain. However, complementary results suggest that this motif is potentially
      poised for conformational change or in dynamic exchange with other conformations.

PMID- 24668818
TI  - Characterization of the testis-specific proteasome subunit alpha4s in mammals.
AB  - The 26 S proteasome is responsible for regulated proteolysis in eukaryotic cells.
      It is composed of one 20 S core particle (CP) flanked by one or two 19 S
      regulatory particles. The CP is composed of seven different alpha-type subunits
      (alpha1-alpha7) and seven different beta-type subunits, three of which are
      catalytic. Vertebrates encode four additional catalytic beta subunits that are
      expressed predominantly in immune tissues and produce distinct subtypes of CPs
      particularly well suited for the acquired immune system. In contrast, the
      diversity of alpha subunits remains poorly understood. Recently, another alpha
      subunit, referred to as alpha4s, was reported. However, little is known about
      alpha4s. Here we provide a detailed characterization of alpha4s and the alpha4s
      containing CP. alpha4s is exclusively expressed in germ cells that enter the
      meiotic prophase and is incorporated into the CP in place of alpha4. A comparison
      of structural models revealed that the differences in the primary sequences
      between alpha4 and alpha4s are located on the outer surface of the CP, suggesting
      that alpha4s interacts with specific molecules via these unique regions. alpha4s
      containing CPs account for the majority of the CPs in mouse sperm. The catalytic
      beta subunits in the alpha4s-containing CP are beta1, beta2, and beta5, and
      immunosubunits are not included in the alpha4s-containing CP. alpha4s-containing
      CPs have a set of peptidase activities almost identical to those of alpha4
      containing CPs. Our results provide a basis for understanding the role of alpha4s
      and male germ cell-specific proteasomes in mammals. 

PMID- 24668819
TI  - Polymeric scaffolds as stem cell carriers in bone repair.
AB  - Although bone has a high potential to regenerate itself after damage and injury,
      the efficacious repair of large bone defects resulting from resection, trauma or
      non-union fractures still requires the implantation of bone grafts. Materials
      science, in conjunction with biotechnology, can satisfy these needs by developing
      artificial bones, synthetic substitutes and organ implants. In particular, recent
      advances in polymer science have provided several innovations, underlying the
      increasing importance of macromolecules in this field. To address the increasing
      need for improved bone substitutes, tissue engineering seeks to create synthetic,
      three-dimensional scaffolds made from polymeric materials, incorporating stem
      cells and growth factors, to induce new bone tissue formation. Polymeric
      materials have shown a great affinity for cell transplantation and
      differentiation and, moreover, their structure can be tuned in order to maintain
      an adequate mechanical resistance and contemporarily be fully bioresorbable. This
      review emphasizes recent progress in polymer science that allows relaible
      polymeric scaffolds to be synthesized for stem cell growth in bone regeneration.

PMID- 24668817
TI  - Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures
      compromise the cytostatic activity of the anticancer drug gemcitabine.
AB  - The intracellular metabolism and cytostatic activity of the anticancer drug
      gemcitabine (2',2'-difluoro-2'-deoxycytidine; dFdC) was severely compromised in
      Mycoplasma hyorhinis-infected tumor cell cultures. Pronounced deamination of dFdC
      to its less cytostatic metabolite 2',2'-difluoro-2'-deoxyuridine was observed,
      both in cell extracts and spent culture medium (i.e. tumor cell-free but
      mycoplasma-containing) of mycoplasma-infected tumor cells. This indicates that
      the decreased antiproliferative activity of dFdC in such cells is attributed to a
      mycoplasma cytidine deaminase causing rapid drug catabolism. Indeed, the
      cytostatic activity of gemcitabine could be restored by the co-administration of
      tetrahydrouridine (a potent cytidine deaminase inhibitor). Additionally,
      mycoplasma-derived pyrimidine nucleoside phosphorylase (PyNP) activity indirectly
      potentiated deamination of dFdC: the natural pyrimidine nucleosides uridine, 2'
      deoxyuridine and thymidine inhibited mycoplasma-associated dFdC deamination but
      were efficiently catabolized (removed) by mycoplasma PyNP. The markedly lower
      anabolism and related cytostatic activity of dFdC in mycoplasma-infected tumor
      cells was therefore also (partially) restored by a specific TP/PyNP inhibitor
      (TPI), or by exogenous thymidine. Consequently, no effect on the cytostatic
      activity of dFdC was observed in tumor cell cultures infected with a PyNP
      deficient Mycoplasma pneumoniae strain. Because it has been reported that some
      commensal mycoplasma species (including M. hyorhinis) preferentially colonize
      tumor tissue in cancer patients, our findings suggest that the presence of
      mycoplasmas in the tumor microenvironment could be a limiting factor for the
      anticancer efficiency of dFdC-based chemotherapy. Accordingly, a significantly
      decreased antitumor effect of dFdC was observed in mice bearing M. hyorhinis
      infected murine mammary FM3A tumors compared with uninfected tumors. 

PMID- 24668827
TI  - Metal-free photochemical aromatic perfluoroalkylation of alpha-cyano
      arylacetates.
AB  - We report here an operationally simple protocol for the direct aromatic
      perfluoroalkylation and trifluoromethylation of alpha-cyano arylacetates. This
      metal-free approach, which occurs at ambient temperature and under visible-light
      irradiation, is driven by the photochemical activity of electron donor-acceptor
      (EDA) complexes, formed in situ by the interaction of transiently generated
      enolates and perfluoroalkyl iodides. Preliminary mechanistic studies are
      reported. 

PMID- 24668828
TI  - Chondrodysplasia punctata associated with maternal Sjogren syndrome.

PMID- 24668829
TI  - Ultrastructure of the sperm axoneme and molecular analysis of axonemal dynein in
      Ephemeroptera (Insecta).
AB  - The Ephemeroptera sperm axoneme is devoid of outer dynein arms (ODA) and exhibits
      a pronounced modification of the central pair complex (CPC), which is substituted
      by the central sheath (CS): a tubular element of unknown molecular composition.
      We performed a detailed ultrastructural analysis of sperm axonemes in the genera
      Cloeon and Ecdyonurus using quick-freeze, deep-etch electron microscopy, showing
      that the loss of the conventional CPC is not only concomitant with the loss of
      ODA, but also with a substantial modification in the longitudinal distribution of
      both radial spokes (RS) and inner dynein arms (IDA). Such structures are no
      longer distributed following the alternation of different repeats as in the 9 + 2
      axoneme, but instead share a 32 nm longitudinal repeat: a multiple of the 8 nm
      repeat observed along the CS wall. Differently from the conventional CPC, the CS
      and the surrounding RS possess a ninefold symmetry, coherently with the three
      dimensional pattern of motility observed in Cloeon free spermatozoa. Biochemical
      analyses revealed that ultrastructural modifications are concomitant with a
      reduced complexity of the IDA heavy chain complement. We propose that these
      structural and molecular modifications might be related to the relief from the
      evolutionary constraints imposed by the CPC on the basal 9 + 9 + 2 axoneme and
      could also represent the minimal set compatible with flagellar beating and
      progressive motility mechanically regulated as suggested by the geometric clutch
      hypothesis. (c) 2014 Wiley Periodicals, Inc.

PMID- 24668830
TI  - Electrical tweezer for highly parallelized electrorotation measurements over a
      wide frequency bandwidth.
AB  - Electrorotation (ROT) is a powerful tool for characterizing the dielectric
      properties of cells and bioparticles. However, its application has been somewhat
      limited by the need to mitigate disruptions to particle rotation by translation
      under positive DEP and by frictional interactions with the substrate. While these
      disruptions may be overcome by implementing particle positioning schemes or field
      cages, these methods restrict the frequency bandwidth to the negative DEP range
      and permit only single particle measurements within a limited spatial extent of
      the device geometry away from field nonuniformities. Herein, we present an
      electrical tweezer methodology based on a sequence of electrical signals,
      composed of negative DEP using 180-degree phase-shifted fields for trapping and
      levitation of the particles, followed by 90-degree phase-shifted fields over a
      wide frequency bandwidth for highly parallelized electrorotation measurements.
      Through field simulations of the rotating electrical field under this wave
      sequence, we illustrate the enhanced spatial extent for electrorotation
      measurements, with no limitations to frequency bandwidth. We apply this
      methodology to characterize subtle modifications in morphology and
      electrophysiology of Cryptosporidium parvum with varying degrees of heat
      treatment, in terms of shifts in the electrorotation spectra over the 0.05-40 MHz
      region. Given the single particle sensitivity and the ability for highly
      parallelized electrorotation measurements, we envision its application toward
      characterizing heterogeneous subpopulations of microbial and stem cells.

PMID- 24668831
TI  - Prospective controlled study to evaluate cryocontact therapy for infantile
      haemangioma in preterm infants.

PMID- 24668832
TI  - The risk for hyperoxaemia after apnoea, bradycardia and hypoxaemia in preterm
      infants.
AB  - OBJECTIVE: To investigate the occurrence and duration of oxygen saturation (SpO2)
      >=95%, after extra oxygen for apnoea, bradycardia, cyanosis (ABC), and the
      relation with the duration of bradycardia and/or SpO2 <=80%. METHODS: All preterm
      infants <32 weeks' gestation supported with nasal continuous positive airway
      pressure (nCPAP) admitted to our centre were eligible for the study. We
      retrospectively identified all episodes of ABCs. In ABCs where oxygen supply was
      increased, duration and severity of bradycardia (<80 bpm), SpO2 <=80%, SpO2 >=95%
      and their correlation were investigated. RESULTS: In 56 infants, 257 ABCs
      occurred where oxygen supply was increased. SpO2 >=95% occurred after 79%
      (202/257) of the ABCs, duration of extra oxygen supply was longer in ABCs with
      SpO2 >=95% than without SpO2 >=95% (median (IQR) 20 (8-80) vs 2 (2-3) min;
      p<0.001)). The duration of SpO2 >=95% was longer than bradycardia and SpO2 <=80%
      (median (IQR) 13 (4-30) vs 1 (1-1) vs 2 (1-2) min; p<0.001). SpO2 >=95% lasted
      longer when infants were in ambient air than when oxygen was given before the ABC
      occurred (median (IQR)15 (5-38) min vs 6 (3-24) min; p<0.01). CONCLUSIONS: In
      preterm infants supported with nCPAP in the neonatal intensive care unit (NICU),
      SpO2 >=95% frequently occurred when oxygen was increased for ABCs and lasted
      longer than the bradycardia and SpO2 <=80%.

PMID- 24668833
TI  - Midface anomaly in a neonate: nasal-ethmoidal meningocele.

PMID- 24668834
TI  - Is persistent need for supplemental oxygen a good indicator of adverse pulmonary
      outcome in very immature infants?

PMID- 24668835
TI  - Prediction models for neonatal  outcomes: are they useful?  Are they feasible?

PMID- 24668836
TI  - Cerebral reorganization of language and motor control secondary to chronic
      hemispheric vasculopathy in a patient with homozygous sickle-cell disease.

PMID- 24668837
TI  - Teicoplanin for treating MRSA pneumonia.

PMID- 24668838
TI  - Structural diversity in multinuclear Pd(II) assemblies that show low-humidity
      proton conduction.
AB  - Systematic investigation on synergetic effects of geometry, length, denticity,
      and asymmetry of donors was performed through the formation of a series of
      uncommon Pd(II) aggregates by employing the donor in a multicomponent self
      assembly of a cis-blocked 90 degrees  Pd(II) acceptor and a tetratopic donor.
      Some of these assemblies represent the first examples of these types of
      structures, and their formation is not anticipated by only taking the geometry of
      the donor and the acceptor building units into account. Analysis of the crystal
      packing of the X-ray structure revealed several H bonds between the counteranions
      (NO3 (-) ) and water molecules (O?H???O?N). Moreover, H-bonded 3D-networks of
      water are present in the molecular pockets, which show water-adsorption
      properties with some variation in water affinity. Interestingly, these complexes
      exhibit proton conductivity (1.87*10(-5) -6.52*10(-4)  Scm(-1) ) at 296 K and low
      relative humidity (ca. 46 %) with activation energies of 0.29-0.46 eV. Moreover,
      the conductivities further increase with the enhancement of humidity. The ability
      of these assemblies to exhibit proton-conducting properties under low-humidity
      conditions makes these materials highly appealing as electrolytes in batteries
      and in fuel-cell applications. 

PMID- 24668839
TI  - Hibiscus sabdariffa extract lowers blood pressure and improves endothelial
      function.
AB  - Polyphenols from Hibiscus sabdariffa calices were administered to patients with
      metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously
      hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for
      each experimental group). The H. sabdariffa extract improved metabolism,
      displayed potent anti-inflammatory and antioxidant activities, and significantly
      reduced blood pressure in both humans and rats. Diuresis and inhibition of the
      angiotensin I-converting enzyme were found to be less important mechanisms than
      those related to the antioxidant, anti-inflammatory, and endothelium-dependent
      effects to explain the beneficial actions. Notably, polyphenols induced a
      favorable endothelial response that should be considered in the management of
      metabolic cardiovascular risks. 

PMID- 24668840
TI  - Fibroblast growth factor 21: a new liver safeguard.

PMID- 24668841
TI  - Applying human factors principles to alert design increases efficiency and
      reduces prescribing errors in a scenario-based simulation.
AB  - OBJECTIVE: To apply human factors engineering principles to improve alert
      interface design. We hypothesized that incorporating human factors principles
      into alerts would improve usability, reduce workload for prescribers, and reduce
      prescribing errors. MATERIALS AND METHODS: We performed a scenario-based
      simulation study using a counterbalanced, crossover design with 20 Veterans
      Affairs prescribers to compare original versus redesigned alerts. We redesigned
      drug-allergy, drug-drug interaction, and drug-disease alerts based upon human
      factors principles. We assessed usability (learnability of redesign, efficiency,
      satisfaction, and usability errors), perceived workload, and prescribing errors.
      RESULTS: Although prescribers received no training on the design changes,
      prescribers were able to resolve redesigned alerts more efficiently (median
      (IQR): 56 (47) s) compared to the original alerts (85 (71) s; p=0.015). In
      addition, prescribers rated redesigned alerts significantly higher than original
      alerts across several dimensions of satisfaction. Redesigned alerts led to a
      modest but significant reduction in workload (p=0.042) and significantly reduced
      the number of prescribing errors per prescriber (median (range): 2 (1-5) compared
      to original alerts: 4 (1-7); p=0.024). DISCUSSION: Aspects of the redesigned
      alerts that likely contributed to better prescribing include design modifications
      that reduced usability-related errors, providing clinical data closer to the
      point of decision, and displaying alert text in a tabular format. Displaying
      alert text in a tabular format may help prescribers extract information quickly
      and thereby increase responsiveness to alerts. CONCLUSIONS: This simulation study
      provides evidence that applying human factors design principles to medication
      alerts can improve usability and prescribing outcomes.

PMID- 24668843
TI  - Segmental composite porous scaffolds with either osteogenesis or anti-bone
      resorption properties tested in a rabbit ulna defect model.
AB  - A functional biomaterial with a therapeutic effect is desirable as an adjuvant
      therapy to enhance bone formation and prevent local recurrence of bone tumours,
      especially when the resection margins are not identifiable. In this study, novel
      composite materials were developed with dual properties of osteopromotion and
      bone resorption to mimic the tumour inhibition effect, including water-soluble
      phosphorylated chitosan (P-chitosan) for increasing osteoblasts activity and
      disodium (1 -> 4)-2-deoxy-2-sulphoamino-beta-d-glucopyranuronan (S-chitosan) for
      inhibiting bone resorption activity. First, P-chitosan and S-chitosan were
      respectively incorporated into two kinds of PLGA/TCP-based scaffold, i.e. PLGA
      TCP-P-chitosan (P/T/P-chitosan) and PLGA-TCP-S-chitosan (P/T/S-chitosan)
      scaffolds. We subsequently tested combined scaffolds of PLGA-TCP-P-S-P-chitosan
      (P/T/PSP-chitosan) made of P/T/P-chitosan and P/T/S-chitosan to assess their
      integral effect, on enhancement of bone formation with P/T/P-chitosan and
      inhibition of tissue regeneration with P/T/S-chitosan, in an established rabbit
      ulnar bone defect model to imitate bone resection post-bone tumour. To compare
      bone healing in the defects, the P/T/P-chitosan group was regarded as a bone
      formation enhancement group, while the P/T group served as a control. Bone
      mineral density (BMD) in the P/T/P-chitosan and P/T/PSP-chitosan groups were
      found to be significantly higher than those in the P/T group, while that in the
      P/T/P-chitosan group was greater than that in the P/T/PSP-chitosan group (p <
      0.05). These findings demonstrated that P/T/PSP-chitosan scaffolds possessed more
      osteogenic potential than the P/T scaffold but less osteogenic effect than the
      P/T/P-chitosan scaffold, as the S-chitosan component inhibited the activities of
      osteoblasts for bone formation. These findings implied a dual function of the
      designed P/T/PSP-chitosan for further preclinical validation and potential
      applications in the prevention of local recurrence and for enhancing bone repair
      after bone tumour resection. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668844
TI  - Fundamental limitations for electroluminescence in organic dual-gate field-effect
      transistors.
AB  - A dual-gate organic field-effect transistor is investigated for electrically
      pumped lasing. The two gates can independently accumulate electrons and holes,
      yielding current densities exceeding the lasing threshold. Here, the aim is to
      force the electrons and holes to recombine by confining the charges in a single
      semiconducting film. It is found that independent hole and electron accumulation
      is mutually exclusive with vertical recombination and light emission. 

PMID- 24668845
TI  - Successful treatment of intravenously abused oral Opana ER-induced thrombotic
      microangiopathy without plasma exchange.
AB  - In January 2013, the Centers for Disease Control and Prevention reported an
      illness associated with intravenous (IV) abuse of oral Opana ER (oxymorphone) in
      Tennessee. The clinical presentation of this syndrome was reported to resemble
      that of thrombotic thrombocytopenic purpura in the 15 patients reported; 12 were
      treated with plasma exchange. We report a similar case series of 15 patients with
      18 episodes of thrombotic microangiopathy associated with recent IV abuse of oral
      Opana ER. In our series, we demonstrate that therapeutic plasma exchange is
      unnecessary; supportive care and treatment of underlying infections and renal
      dysfunction (without use of plasma exchange) resulted in clinical improvement in
      all patients. Thus, it appears that plasma exchange with associated costs and
      risks can be safely omitted in patients with thrombotic microangiopathy resulting
      from IV abuse of oral Opana ER.

PMID- 24668846
TI  - In vivo chemoembolization and magnetic resonance imaging of liver tumors by using
      iron oxide nanoshell/doxorubicin/poly(vinyl alcohol) hybrid composites.
AB  - A hybrid composite made up of superparamagnetic iron oxide nanoshells
      encapsulating the anticancer drug doxorubicin and bound together by poly(vinyl
      alcohol) was developed. Transcatheter arterial delivery in an in vivo liver tumor
      model led to embolization of the liver tumor blood vessels. Embolization was
      followed by disassembly of the composite. The nanoshells were then able to pass
      through the leaky tumor vasculature into the tumor tissue, thereby leading to
      slow and sustained release of the drug. As well as being relatively noncytotoxic,
      the composite was responsive to magnetic resonance imaging, thus making it a
      potentially useful theranostic agent. 

PMID- 24668847
TI  - Further delineation of eye manifestations in homozygous 15q13.3 microdeletions
      including TRPM1: a differential diagnosis of ceroid lipofuscinosis.
AB  - The 15q13.3 heterozygous microdeletion is a fairly common microdeletion syndrome
      with marked clinical variability and incomplete penetrance. The average size of
      the deletion, which comprises six genes including CHRNA7, is 1.5 Mb. CHRNA7 has
      been identified as the gene responsible for the neurological phenotype in this
      microdeletion syndrome. Only seven patients with a homozygous microdeletion that
      includes at least CHRNA7, and is inherited from both parents have been described
      in the literature. The aim of this study was to further describe the distinctive
      eye manifestations from the analysis in the three French patients diagnosed with
      the classical 1.5 Mb homozygous microdeletion. Patients' ages ranged from 30
      months to 9 years, and included one sib pair. They all displayed a remarkably
      severe identifiable clinical phenotype that included congenital blindness and
      convulsive encephalopathy with inconstant abnormal movements. The
      ophthalmological examination revealed a lack of eye tracking, optic nerve pallor,
      an immature response with increased latencies with no response to the
      checkerboard stimulations at the visual evoked potential examination, and a
      distinctive retina dystrophy with a negative electroretinogram in which the "b"
      wave was smaller than the "a" wave after a dark adapted pupil and bright flash in
      all patients. Clear genotype-phenotype correlations emerged, showing that this
      eye phenotype was secondary to homozygous deletion of TRPM1, the gene responsible
      for autosomal recessive congenital stationary night blindness. The main
      differential diagnosis is ceroid lipofuscinosis.

PMID- 24668848
TI  - Characteristics of venom allergic reactions in Turkish beekeepers and alternative
      treatment modalities.
AB  - BACKGROUND: The objective of this work was to determine the characteristics of
      allergic reactions that may occur after a bee sting and alternative treatment
      methods in Turkish beekeepers. METHODS: A written questionnaire was administered
      to beekeepers from the Ordu, Samsun, Sinop, Amasya, and Corum provinces located
      in the Central Black Sea Region of Turkey. RESULTS: The study included 301
      beekeepers, 295 (98%) of whom were male. Their mean age was 48.2 +/- 11.5 years.
      The mean beekeeping duration was 15.3 +/- 10.5 years. A total of 270 participants
      (89.9%) had a history of bee stings in the previous 12 months. Systemic
      reactions, large local reactions, and local reactions were seen in 21 (6.9%), 193
      (64.1%), and 12 (4.0%) beekeepers, respectively. The face was the most frequently
      stung body site, and swelling generally occurred in the eyelids. The size of the
      swellings decreased within 12 to 24 hours in 259 (86.1%) beekeepers. The size of
      the swellings was 1 * 2 cm in diameter in 157 (52.2%) beekeepers. Natural
      protection against bee stings had developed by 12 months in 140 (46.5%)
      beekeepers. In total, 61.5% of the beekeepers applied alternative treatments (eg,
      garlic, onion water, yogurt), whereas 14.0% (3/21) were admitted to a hospital
      with a systemic reaction. In total, 10.6% and 14.2% of beekeepers were aware of
      adrenaline auto-injector and venom immunotherapy, respectively. CONCLUSION: This
      study indicates insufficient knowledge and attitudes among Turkish beekeepers
      regarding bee sting reactions.

PMID- 24668849
TI  - Immature granulocyte count in peripheral blood by the Sysmex haematology XN
      series compared to microscopic differentiation.

PMID- 24668851
TI  - Microvilli as markers of disordered apical-membrane trafficking and assembly:
      bowel and liver.

PMID- 24668850
TI  - Dietary deprivation of each essential amino acid induces differential systemic
      adaptive responses in mice.
AB  - SCOPE: Dietary deprivation of essential amino acids (EAAs) in mammals is known to
      cause reductions in food intake and body weight. The aim of this study was to
      determine whether and how mice respond to deprivation of individual EAA species.
      METHODS AND RESULTS: Dietary deprivation of any single EAA (not non-EAA) in mice
      led to progressive weight loss in the order of Ile(-) > Val(-) > Thr(-) > Leu(-)
      > Trp(-) > His(-) > Phe(-) > Met(-) > Lys(-) , which correlated with the
      reduction in food intake. Decreased levels of the deprived EAAs as well as
      increased levels of all or some of the other amino acids were detected in the
      serum, although these levels differed among the diets examined. Serum
      biochemistry identified significant increases in creatine phosphokinase, blood
      urea nitrogen, alanine aminotransferase, and aspartate aminotransferase, and
      decreases in glucose and triglycerides; computed tomography revealed a marked
      reduction in abdominal/femoral fat and muscle depots; histology identified
      diffuse myofiber atrophy in the rectus femoris muscle, all in that approximate
      order. In contrast, amino acid response, autophagy, and ubiquitination marker
      genes as well as amino acid transporter genes were induced in both deprived EAA
      specific and tissue-specific manners. CONCLUSION: Dietary deprivation of
      individual EAAs induced systemic adaptive responses that differed in magnitude
      and molecular machinery.

PMID- 24668852
TI  - Prestaining of glycoproteins in sodium dodecyl sulfate polyacrylamide gels by
      dansylhydrazine.
AB  - A new fluorescent prestaining method for gel-separated glycoproteins in 1D and 2D
      SDS-PAGE was developed by using dansylhydrazine in this study. The prestained
      gels could be easily imaged after electrophoresis without any time-consuming
      steps needed for poststains. As low as 4-8 ng glycoproteins (transferrin, alpha1
      acid glycoprotein) could be selectively detected, which is comparable to that of
      Pro-Q Emerald 488, one of the most commonly used glycoprotein stain. In addition,
      a subsequent study of deglycosylation, glycoprotein affinity isolation, and LC
      MS/MS analysis was performed to confirm the specificity of the newly developed
      method.

PMID- 24668853
TI  - The mechanisms of carnosic acid attenuates tumor necrosis factor-alpha-mediated
      inflammation and insulin resistance in 3T3-L1 adipocytes.
AB  - SCOPE: Insulin resistance has been linked to a low-grade chronic inflammatory
      response. Carnosic acid (CA), which is found in rosemary, has been reported to
      have antioxidant, anti-inflammation, and anti-adipogenic properties. Here, we
      examined the effects of CA on inflammation and insulin resistance in 3T3-L1
      adipocytes treated with tumor necrosis factor-alpha (TNF-alpha). METHODS AND
      RESULTS: CA attenuated the TNF-alpha-induced mRNA expression of inflammatory
      genes, including IL-6 and monocyte chemoattractant protein-1. CA also attenuated
      the TNF-alpha-mediated activation of extracellular signal-regulated kinase, c-Jun
      NH2-terminal kinase, and c-Jun; the phosphorylation of inhibitor-kappaB (IkappaB)
      kinase (IKK)alpha/beta, the phosphorylation and degradation of IkappaBalpha, the
      nuclear translocation of p65, and the DNA-binding activity of NF-kappaB and AP-1.
      CA or PP242 (an mTOR inhibitor) suppressed the TNF-alpha-induced protein
      expression of mTOR, p70S6K, eIF4E, and IL-6. Moreover, CA attenuated the TNF
      alpha-mediated suppression of peroxisome proliferator-activated receptor gamma,
      adiponectin, and adipocyte protein 2. CA reversed the TNF-alpha-mediated
      suppression of insulin-stimulated glucose uptake and the phosphorylation of
      Tyr(632) insulin receptor substrate-1 (IRS-1), Akt, and FoxO1, but decreased the
      TNF-alpha-induced phosphorylation of Ser(307) IRS-1 and total FoxO1. CONCLUSION:
      CA attenuates TNF-alpha-mediated inflammation via inhibition of NF-kappaB and AP
      1 pathways and insulin resistance via Akt-dependent FoxO1 signaling in 3T3-L1
      adipocytes.

PMID- 24668854
TI  - Rhodium-catalyzed direct amination of arenes with nitrosobenzenes: a new route to
      diarylamines.
AB  - A Rh(III) -catalyzed addition of aryl C?H bonds to nitrosobenzenes, followed by
      cleavage of the resulting hydroxylamines in situ, has been reported. Different
      directing groups, such as N-based heterocycles and ketoximes, can be used in this
      C?H amination process, providing valuable diarylamines in excellent yields. Most
      importantly, this process provides a new method for attaching arylamine groups to
      aromatic rings. 

PMID- 24668855
TI  - The art of communication during consultations.

PMID- 24668857
TI  - Fluorescence lifetime excitation cytometry by kinetic dithering.
AB  - Flow cytometers are powerful high-throughput devices that capture spectroscopic
      information from individual particles or cells. These instruments provide a means
      of multi-parametric analyses for various cellular biomarkers or labeled
      organelles and cellular proteins. However, the spectral overlap of fluorophores
      limits the number of fluorophores that can be used simultaneously during
      experimentation. Time-resolved parameters enable the quantification of
      fluorescence decay kinetics, thus circumventing common issues associated with
      intensity-based measurements. This contribution introduces fluorescence lifetime
      excitation cytometry by kinetic dithering (FLECKD) as a method to capture
      multiple fluorescence lifetimes using a hybrid time-domain approach. The FLECKD
      approach excites fluorophores by delivering short pulses of light to cells or
      particles by rapid dithering and facilitates measurement of complex fluorescence
      decay kinetics by flow cytometry. Our simulations demonstrated a resolvable
      fluorescence lifetime value as low as 1.8 ns (+/-0.3 ns) with less than 20%
      absolute error. Using the FLECKD instrument, we measured the shortest average
      fluorescence lifetime value of 2.4 ns and found the system measurement error to
      be +/-0.3 ns (SEM), from hundreds of monodisperse and chemically stable
      fluorescent microspheres. Additionally, we demonstrate the ability to detect two
      distinct excited state lifetimes from fluorophores in single cells using FLECKD.
      This approach presents a new ability to resolve multiple fluorescence lifetimes
      while retaining the fluidic throughput of a cytometry system. The ability to
      discriminate more than one average fluorescence lifetime expands the current
      capabilities of high-throughput and intensity-based cytometry assays as the need
      to tag one single cell with multiple fluorophores is now widespread.

PMID- 24668858
TI  - Single agent lenalidomide three times a week induces hematologic responses in AL
      amyloidosis patients on dialysis.
AB  - The combination of lenalidomide and dexamethasone can produce hematologic
      responses in previously treated patients with AL amyloidosis. Because
      lenalidomide is primarily excreted unchanged by the kidney, adjustments to the
      starting dose of lenalidomide are recommended to provide appropriate drug
      exposure in patients with moderate or severe renal impairment and in patients on
      dialysis. Here, we report on a study of patients with AL amyloidosis on dialysis
      treated with lenalidomide at a dose of 10 mg orally three times a week. Seven
      patients were enrolled. All patients had received prior treatment, with 57%
      receiving prior high-dose melphalan and stem cell transplantation. Two patients
      died before evaluation of response. The most common adverse event was infection;
      no thromboembolic complications were seen. One patient required dose
      modification. Hematologic responses were obtained by four of the five evaluable
      patients. Median overall survival was 18 months. In conclusion, adjusted dose
      lenalidomide was reasonably tolerated and induced sustained hematologic responses
      in previously treated patients with AL amyloidosis on dialysis.

PMID- 24668859
TI  - Polymer solar cells with diketopyrrolopyrrole conjugated polymers as the electron
      donor and electron acceptor.
AB  - A new class of diketopyrrolopyrrole conjugated acceptor polymer incorporating
      thiazoles with low-lying energy levels, high electron mobility, and broad
      absorption to the near infrared region provides a power conversion efficiency of
      2.9% in solar cells with a second diketopyrrolo-pyrrole polymer as the donor. 

PMID- 24668860
TI  - In vitro cellular response to oxidized collagen-PLLA hybrid scaffolds designed
      for the repair of muscular tissue defects and complex incisional hernias.
AB  - Unique poly(l-lactic acid) (PLLA)-based scaffolds were constructed by embedding
      knitted PLLA yarns within a bioresorbable and differentially crosslinked three
      dimensional (3D) oxidized collagen scaffold. The scaffolds were designed
      specifically for the repair of complex incisional abdominal wall hernias and the
      repair of defects within planar muscular tissues, such as the bladder. The
      chemical composition of the collagen matrix and the percentage of scaffold
      infiltration were compared for the different scaffold compositions. The results
      demonstrate that the incorporation of the collagen sponge within the PLLA
      scaffold facilitated bladder smooth muscle cell (bSMC) adhesion and
      proliferation. The highest dose of oxidized collagen (Oxicol) demonstrated better
      cell adhesion, resulting in the largest cell densities and most uniform
      distribution throughout the 3D collagen sponge. This formulation promoted the
      greatest alpha-smooth muscle actin (alphaSMA) expression detected through
      immunohistochemical staining and western blotting. For abdominal wall repair
      applications, the proliferation and differentiation of C2C12 myoblasts and
      myotube formation were studied. Following 7 days of myogenic induction, the
      greatest expression of mRNA of the myogenic markers myogenin and MRF4 was
      observed within the scaffolds with the highest dose of oxidized collagen, 1.5-
      and 3.85-fold greater expressions, respectively, compared to PLLA with unmodified
      collagen. Furthermore, in vitro myotube formation and MyMC expression were
      enhanced in the Oxicol scaffolds. We conclude that the Oxicol scaffold
      formulation with a high-dose oxidized collagen ratio provides enhanced myogenesis
      and alphaSMA, and the biological induction cues necessary to achieve better
      tissue integration, than standard PLLA scaffolds in the treatment of complex
      abdominal wall hernias. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668861
TI  - Confirmed by X-ray crystallography: the B?B one-electron sigma bond.
AB  - Is one electron sufficient to bring about significant sigma bonding between two
      atoms? The chemist's view on the chemical bond is usually tied to the concept of
      shared electron pairs, and not too much experimental evidence exists to challenge
      this firm belief. Whilst species with the unusual one-electron sigma-bonding
      motif between homonuclear atoms have so far been identified mainly by
      spectroscopic evidence, we present herein the first crystallographic
      characterization, augmented by a detailed quantum-chemical validation, for a
      radical anion featuring a B?B one-electron-two-center sigma bond. 

PMID- 24668862
TI  - Hypercaloric diets with increased meal frequency, but not meal size, increase
      intrahepatic triglycerides: a randomized controlled trial.
AB  - American children consume up to 27% of calories from high-fat and high-sugar
      snacks. Both sugar and fat consumption have been implicated as a cause of hepatic
      steatosis and obesity but the effect of meal pattern is largely understudied. We
      hypothesized that a high meal frequency, compared to consuming large meals, is
      detrimental in the accumulation of intrahepatic and abdominal fat. To test this
      hypothesis, we randomized 36 lean, healthy men to a 40% hypercaloric diet for 6
      weeks or a eucaloric control diet and measured intrahepatic triglyceride content
      (IHTG) using proton magnetic resonance spectroscopy ((1) H-MRS), abdominal fat
      using magnetic resonance imaging (MRI), and insulin sensitivity using a
      hyperinsulinemic euglycemic clamp with a glucose isotope tracer before and after
      the diet intervention. The caloric surplus consisted of fat and sugar (high-fat
      high-sugar; HFHS) or sugar only (high-sugar; HS) and was consumed together with,
      or between, the three main meals, thereby increasing meal size or meal frequency.
      All hypercaloric diets similarly increased body mass index (BMI). Increasing meal
      frequency significantly increased IHTG (HFHS mean relative increase of 45%; P =
      0.016 and HS mean relative increase of 110%; P = 0.047), whereas increasing meal
      size did not (2-way analysis of variance [ANOVA] size versus frequency P = 0.03).
      Abdominal fat increased in the HFHS-frequency group (+63.3 +/- 42.8 mL; P =
      0.004) and tended to increase in the HS-frequency group (+46.5 +/- 50.7 mL; P =
      0.08). Hepatic insulin sensitivity tended to decrease in the HFHS-frequency group
      while peripheral insulin sensitivity was not affected. CONCLUSION: A hypercaloric
      diet with high meal frequency increased IHTG and abdominal fat independent of
      caloric content and body weight gain, whereas increasing meal size did not. This
      study suggests that snacking, a common feature in the Western diet, independently
      contributes to hepatic steatosis and obesity. ( TRIAL REGISTRATION:
      www.clinicaltrials.gov; nr.NCT01297738.)

PMID- 24668863
TI  - L1CAM whole gene deletion in a child with L1 syndrome.
AB  - L1 syndrome is a group of overlapping, X-linked disorders caused by mutations in
      L1CAM. Clinical phenotypes within L1 syndrome include X-linked hydrocephalus with
      stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs,
      shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and
      agenesis of the corpus callosum. Over 200 mutations in L1CAM have been reported;
      however, only a few large gene deletions have been observed. We report on a 4
      month-old male with a de novo whole gene deletion of L1CAM presenting with
      congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial
      failure of L1CAM gene sequencing suggested the possibility of a whole gene
      deletion of L1CAM. Further investigation through chromosome microarray analysis
      showed a 62Kb deletion encompassing the first exon of the PDZD4 gene and the
      entire L1CAM gene. Investigations into genotype-phenotype correlations have
      suggested that mutations leading to truncated or absent L1 protein cause more
      severe forms of L1 syndrome. Based on the presentation of the proband and other
      reported patients with whole gene deletions, we provide further evidence that
      L1CAM whole gene deletions result in L1 syndrome with a severe phenotype,
      deletions of PDZD4 do not cause additional manifestations, and that X-linked
      nephrogenic diabetes insipidus reported in a subset of patients with large L1CAM
      deletions results from the loss of AVPR2.

PMID- 24668870
TI  - Freezing capture of polymorphic aggregates of bolaamphiphilic (L)-valine-based
      molecular hydrogelators.
AB  - Nanostructured xerogels have been prepared by the freeze-drying of hydrogels and
      aggregates formed by bolaamphiphilic L-valine derivatives after aging under
      different environmental conditions. A wide variety of shapes and sizes has been
      achieved by a simple methodology. These nanostructures have been studied by SEM
      and WAXD and a dramatic influence of structural flexibility on the kinetics of
      aggregation has been observed. Such flexibility and a modulation of the
      hydrophobic effect have shown a profound influence in the packing of these
      compounds and revealed a high degree of polymorphism. 

PMID- 24668871
TI  - Rapidly maturing field of proteomics: a gateway to studying diseases.
AB  - The proteomics work reported by Smith et al. represents a giant step forward in
      characterizing the cerebrospinal fluid (CSF) proteome in mouse models of human
      diseases. Whereas prior studies were limited to analysis of CSF pools, Smith et
      al. (Proteomics 2014, 14, 1102-1106) base their conclusions on data derived from
      individual mice, thereby capturing a fuller range of the biological diversity
      present. These results underscore how far proteomics has come in the past few
      years, developing into a modern tool with the capacity to remove bottlenecks in
      the study of neuropsychiatric diseases. Past efforts with mass spectrometry (MS)
      have been hampered by limitations in access to CSF samples, and small volumes
      when available. These barriers have been overcome with newer MS platforms and
      advances in sample preparation. We are far closer than before to producing the
      production of clinically useful proteomic data for biomarker discovery and for
      deriving insights into pathogenesis that can lead to more effective treatments
      for many diseases. 

PMID- 24668872
TI  - Comparison Between Sexes of Bone Contusions and Meniscal Tear Patterns in
      Noncontact Anterior Cruciate Ligament Injuries.
AB  - BACKGROUND: Valgus load has been linked to female predominance and mechanism for
      noncontact anterior cruciate ligament (ACL) injuries. Magnetic resonance imaging
      (MRI) studies reporting frequent medial contusions in noncontact ACL injuries
      suggest anterior translation rather than a valgus mechanism. HYPOTHESIS: Bone
      contusion and meniscal tear patterns differ between sexes. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: This study included a review of clinic
      notes, operative reports, and MRI of patients younger than 20 years who underwent
      acute primary ACL reconstruction for a noncontact injury between January 1, 2005,
      and January 1, 2010. A blinded musculoskeletal MRI radiologist reported the
      incidence of medial and lateral femoral and tibial bone contusions on MRI, as
      well as the severity of medial versus lateral tibial contusions. The location of
      the bone contusions and meniscal tears and the maximal tibial contusion severity
      were compared through chi-square analysis (statistical significance, P < .05).
      RESULTS: A total of 73 patients met inclusion criteria: 28 males, 45 females;
      mean age, 16.1 +/- 1.7 years (males), 16.5 +/- 1.7 years (females). No
      significant differences were noted between sexes for location of tibial
      contusions (P = .32), femoral contusions (P = .44), or meniscal tears (P = .715).
      The most common tibial contusion pattern was to have both medial and lateral
      tibial contusions, in both male (57%) and female (60%) patients. The most common
      femoral contusion pattern was lateral only in females (62%) and both medial and
      lateral in males (50%). The percentage of female (29%) and male (29%) patients
      with isolated medial meniscal tears was nearly identical. More males (29%) than
      females (18%) had isolated lateral meniscal tears (P = .72). No significant
      difference in the relative severity of the tibial contusions was noted (P =
      .246). The lateral tibial contusion was rated as being more severe than the
      medial in the majority of females (64%) and males (57%). CONCLUSION: No
      significant differences were detected between sexes with noncontact ACL injuries
      for location of tibial or femoral contusions or meniscal tears or for severity of
      medial versus lateral tibial contusions. The MRI data were not consistent with
      the valgus collapse mechanism of injury.

PMID- 24668873
TI  - Tendon Contraction After Cyclic Elongation Is an Age-Dependent Phenomenon: In
      Vitro and In Vivo Comparisons.
AB  - BACKGROUND: Tendons are viscoelastic tissues that deform (elongate) in response
      to cyclic loading. However, the ability of a tendon to recover this elongation is
      unknown. HYPOTHESIS: Tendon length significantly increases after in vivo or in
      vitro cyclic loading, and the ability to return to its original length through a
      cell-mediated contraction mechanism is an age-dependent phenomenon. STUDY DESIGN:
      Controlled laboratory study. METHODS: In vitro, rat tail tendon fascicles (RTTfs)
      from Sprague-Dawley rats of 3 age groups (1, 3, and 12 months) underwent 2%
      cyclic strain at 0.17 Hz for 2 hours, and the percentages of elongation were
      determined. After loading, the RTTfs were suspended for 3 days under tissue
      culture conditions and photographed daily to determine the amount of length
      contraction. In vivo, healthy male participants (n = 29; age, 19-49 years) had
      lateral, single-legged weightbearing radiographs taken of the knee at 60 degrees 
      of flexion immediately before, immediately after, and 24 hours after completing
      eccentric quadriceps loading exercises on the dominant leg to fatigue.
      Measurements of patellar tendon length were taken from the radiographs, and the
      percentages of tendon elongation and subsequent contraction were calculated.
      RESULTS: In vitro, cyclic loading increased the length of all RTTfs, with
      specimens from younger (1 and 3 months) rats demonstrating significantly greater
      elongation than those from older (12 months) rats (P = .009). The RTTfs
      contracted to their original length significantly faster (P < .001) and in an age
      dependent fashion, with younger animals contracting faster. In vivo, repetitive
      eccentric loading exercises significantly increased patellar tendon length (P <
      .001). Patellar tendon length decreased 24 hours after exercises (P < .001) but
      did not recover completely (P < .001). There was a weak but significant (R (2) =
      0.203, P = .014) linear correlation between the amount of tendon contraction and
      age, with younger participants (<30 years) demonstrating significantly more
      contraction (P = .014) at 24 hours than older participants (>30 years).
      CONCLUSION: Cyclic tendon loading results in a significant increase in tendon
      elongation under both in vitro and in vivo conditions. Tendons in both conditions
      demonstrated an incomplete return to their original length after 24 hours, and
      the extent of this return was age dependent. CLINICAL RELEVANCE: The age- and
      time-dependent contraction of tendons, elongated after repetitive loading, could
      result in transient alterations in the mechanobiological environment of tendon
      cells. This, in turn, could induce the onset of catabolic changes associated with
      the pathogenesis of tendinopathy. These results suggest the importance of
      allowing time for contraction between bouts of repetitive exercise and may
      explain why age is a predisposing factor in tendinopathy.

PMID- 24668875
TI  - A deformable nanoplasmonic membrane reveals universal correlations between
      plasmon resonance and surface enhanced Raman scattering.
AB  - A quantitative correlation between plasmon resonance and surface enhanced Raman
      scattering (SERS) signals is revealed by using a novel active plasmonic method,
      that is, a deformable nanoplasmonic membrane. A single SERS peak has the maximum
      gain at the corresponding plasmon resonance wavelength, which has the maximum
      extinction product of an excitation and the corresponding Raman scattering
      wavelengths. 

PMID- 24668874
TI  - Ethylene negatively regulates aluminium-induced malate efflux from wheat roots
      and tobacco cells transformed with TaALMT1.
AB  - An important mechanism for Al(3+) tolerance in wheat is exudation of malate
      anions from the root apex through activation of malate-permeable TaALMT1
      channels. Here, the effect of ethylene on Al(3+)-activated efflux of malate was
      investigated using Al(3+)-tolerant wheat genotype ET8, which has high expression
      of TaALMT1. Exposure of ET8 plants to Al(3+) enhanced ethylene evolution in root
      apices. Treatment with the ethylene synthesis precursor 1-aminocyclopropane-1
      carboxylic acid (ACC) and ethylene gas suppressed Al(3+)-induced malate efflux
      from root apices, whereas the intracellular malate concentrations in roots were
      not affected. Malate efflux from root apices was enhanced in the presence of
      Al(3+) by two antagonists of ethylene biosynthesis, aminoethoxyvinylglycine (AVG)
      and 2-aminoisobutyric acid (AIB). An increase in Al accumulation in root apices
      was observed when treated with ACC, whereas AVG and AIB suppressed Al
      accumulation in root apices. Al(3+)-induced inhibition of root elongation was
      ameliorated by pretreatment with AIB. In addition, ethylene donor (Ethrel) also
      inhibited Al(3+)-induced malate efflux from tobacco cells transformed with
      TaALMT1. ACC and the anion-channel blocker niflumate had a similar and non
      additive effect on Al-induced malate efflux from root apices. Treatment of ET8
      plants with ACC enhanced expression of TaALMT1, suggesting that the inhibitory
      effect of ethylene on Al-induced malate efflux is unlikely to occur at the
      transcriptional level. These findings indicate that ethylene may behave as a
      negative regulator of Al(3+)-induced malate efflux by targeting TaALMT1-mediated
      malate efflux by an unknown mechanism. 

PMID- 24668876
TI  - Structural polymorphism analysis of Chinese Mongolian ethnic group revealed by a
      new STR panel: genetic relationship to other groups.
AB  - Mongolian is the eighth largest ethnic minority on Chinese population data
      according to the 2010 census. In the present study, we presented the first report
      about the allelic frequencies and forensic statistical parameters at the 21 new
      STRs and analyzed linkage disequilibrium of pairwise loci in the Mongolian ethnic
      minority, China. Hardy-Weinberg equilibrium tests demonstrated no significant
      deviations except for the D1S1627 locus. The cumulative power of discrimination
      and power of exclusion of all the loci are 0.9999999999999999992576 and
      0.9999997528, respectively. The results of analysis of molecular variance showed
      that significant differences between the Mongolian and the other eight
      populations were found at 1-9 STR loci. In population genetics, the results of
      principal component analysis, structure analysis, and phylogenetic reconstruction
      analysis indicated shorter genetic distance between the Mongolian group and the
      Ningxia Han. All the results suggest that the 21 new STR loci will contribute to
      Chinese population genetics and forensic caseworks in the Mongolian group.

PMID- 24668877
TI  - One in eight deaths is due to air pollution, says WHO.

PMID- 24668878
TI  - Carbon fibers: precursor systems, processing, structure, and properties.
AB  - This Review gives an overview of precursor systems, their processing, and the
      final precursor-dependent structure of carbon fibers (CFs) including new
      developments in precursor systems for low-cost CFs. The following CF precursor
      systems are discussed: poly(acrylonitrile)-based copolymers, pitch, cellulose,
      lignin, poly(ethylene), and new synthetic polymeric precursors for high-end CFs.
      In addition, structure-property relationships and the different models for
      describing both the structure and morphology of CFs will be presented. 

PMID- 24668879
TI  - Craniofacial and dental development in Costello syndrome.
AB  - Costello syndrome (CS) is a RASopathy characterized by a wide range of cardiac,
      musculoskeletal, dermatological, and developmental abnormalities. The RASopathies
      are defined as a group of syndromes caused by activated Ras/mitogen-activated
      protein kinase (MAPK) signaling. Specifically, CS is caused by activating
      mutations in HRAS. Although receptor tyrosine kinase (RTK) signaling, which is
      upstream of Ras/MAPK, is known to play a critical role in craniofacial and dental
      development, the craniofacial and dental features of CS have not been
      systematically defined in a large group of individuals. In order to address this
      gap in our understanding and fully characterize the CS phenotype, we evaluated
      the craniofacial and dental phenotype in a large cohort (n = 41) of CS
      individuals. We confirmed that the craniofacial features common in CS include
      macrocephaly, bitemporal narrowing, convex facial profile, full cheeks, and large
      mouth. Additionally, CS patients have a characteristic dental phenotype that
      includes malocclusion with anterior open bite and posterior crossbite, enamel
      hypo-mineralization, delayed tooth development and eruption, gingival
      hyperplasia, thickening of the alveolar ridge, and high palate. Comparison of the
      craniofacial and dental phenotype in CS with other RASopathies, such as cardio
      facio-cutaneous syndrome (CFC), provides insight into the complexities of
      Ras/MAPK signaling in human craniofacial and dental development.

PMID- 24668881
TI  - Main-chain organometallic microporous polymers bearing triphenylene-tris(N
      heterocyclic carbene)-gold species: catalytic properties.
AB  - Two triphenylene-based tris(N-heterocyclic carbene)-gold-acetylide main-chain
      organometallic microporous polymers (MOMPs) were obtained and fully
      characterized. Both materials show spherical shapes, and their size is highly
      dependent on the type of acetylene used in the synthetic protocol. The new solids
      were tested in the catalytic reduction of nitroarenes with NaBH4 and in the three
      component Strecker reaction for the synthesis of alpha-aminonitriles, and showed
      high activity in both processes. Whereas the activity of the solids in the
      reduction of nitroarenes may be attributed to the formation of Au nanoparticles
      due to the use of NaBH4 as reducing agent, the activity in the Strecker reaction
      may originate from the Lewis acidic activation of the ketone or imine on
      coordination to Au. 

PMID- 24668880
TI  - Engineering liver.
AB  - Interest in "engineering liver" arises from multiple communities: therapeutic
      replacement; mechanistic models of human processes; and drug safety and efficacy
      studies. An explosion of micro- and nanofabrication, biomaterials, microfluidic,
      and other technologies potentially affords unprecedented opportunity to create
      microphysiological models of the human liver, but engineering design principles
      for how to deploy these tools effectively toward specific applications, including
      how to define the essential constraints of any given application (available
      sources of cells, acceptable cost, and user-friendliness), are still emerging.
      Arguably less appreciated is the parallel growth in computational systems biology
      approaches toward these same problems-particularly in parsing complex disease
      processes from clinical material, building models of response networks, and in
      how to interpret the growing compendium of data on drug efficacy and toxicology
      in patient populations. Here, we provide insight into how the complementary paths
      of engineering liver-experimental and computational-are beginning to interplay
      toward greater illumination of human disease states and technologies for drug
      development.

PMID- 24668882
TI  - Experimental evidence of rapid water transport through carbon nanotubes embedded
      in polymeric desalination membranes.
AB  - As water molecules permeate ultrafast through carbon nanotubes (CNTs), many
      studies have prepared CNTs-based membranes for water purification as well as
      desalination, particularly focusing on high flux membranes. Among them,
      vertically aligned CNTs membranes with ultrahigh water flux have been
      successfully demonstrated for fundamental studies, but they lack scalability for
      bulk production and sufficiently high salt rejection. CNTs embedded in polymeric
      desalination membranes, i.e., polyamide thin-film composite (TFC) membranes, can
      improve water flux without any loss of salt rejection. This improved flux is
      achieved by enhancing the dispersion properties of CNTs in diamine aqueous
      solution and also by using cap-opened CNTs. Hydrophilic CNTs were prepared by
      wrapping CNT walls via bio-inspired surface modification using dopamine solution.
      Cap-opening of pristine CNTs is performed by using a thermo-oxidative process. As
      a result, hydrophilic, cap-opened CNTs-embedded polyamide TFC membranes are
      successfully prepared, which show much higher water flux than pristine polyamide
      TFC membrane. On the other hand, less-disperse, less cap-opened CNTs-embedded TFC
      membranes do not show any flux improvement and rather lead to lower salt
      rejection properties. 

PMID- 24668883
TI  - Prediction of partition coefficients for complex environmental contaminants:
      Validation of COSMOtherm, ABSOLV, and SPARC.
AB  - Prediction of partition coefficients is essential for screening of
      environmentally relevant compounds. Prediction methods using only the molecular
      structure as input are especially useful for this purpose. In the present study,
      the authors validated 3 prediction method-COSMOtherm, ABSOLV, and SPARC-which are
      based on more mechanistic approaches than most other quantitative structure
      activity relationships. Validation was based on a consistent experimental data
      set of up to 270 compounds, mostly pesticides and flame retardants. The
      validation systems included 3 gas chromatographic (GC) columns and 4
      liquid/liquid systems that represent all relevant types of intermolecular
      interactions. Results revealed that the overall prediction accuracy of COSMOtherm
      and ABSOLV is comparable, whereas SPARC performance is substantially lower than
      the other methods. For instance, the root mean squared error for the 4
      liquid/liquid partition coefficients was 0.65 log units to 0.93 log units for
      COSMOtherm, 0.64 log units to 0.95 log units for ABSOLV, and 1.43 to 2.85 log
      units for SPARC. In addition, version and parameterization influences of
      COSMOtherm on the prediction accuracy were determined.

PMID- 24668885
TI  - Construction of quaternary stereogenic carbon centers through copper-catalyzed
      enantioselective allylic cross-coupling with alkylboranes.
AB  - A combination of an in situ generated chiral Cu(I) /DTBM-MeO-BIPHEP catalyst
      system and EtOK enabled the enantioselective SN 2'-type allylic cross-coupling
      between alkylborane reagents and gamma,gamma-disubstituted primary allyl
      chlorides with enantiocontrol at a useful level. The reaction generates a
      stereogenic quaternary carbon center having three sp(3) -alkyl groups and a vinyl
      group. This protocol allowed the use of terminal alkenes as nucleophile
      precursors, thus representing a formal reductive allylic cross-coupling of
      terminal alkenes. A reaction pathway involving addition/elimination of a neutral
      alkylcopper(I) species with the allyl chloride substrate is proposed. 

PMID- 24668884
TI  - Enzyme 15-lipoxygenase 1 promotes hypoxia-inducible factor 1alpha turnover and
      reduces vascular endothelial growth factor expression: implications for
      angiogenesis.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) is the regulatory subunit of the
      heterodimeric HIF-1 that plays a critical role in transcriptional regulation of
      genes in angiogenesis and hypoxic adaptation, while fatty acid metabolism
      mediated by lipoxygenases has been implicated in a variety of pathogeneses,
      including cancers. In this study, we report that 15-lipoxygenase 1 (15-LO1), a
      key member of the lipoxygenase family, promotes HIF-1alpha ubiquitination and
      degradation. Altering the level of 15-LO1 yields inverse changes in HIF-1alpha
      and HIF-1 transcriptional activity, under both normoxia and hypoxia, and even in
      CoCl2 -treated cells where HIF-1alpha has been artificially elevated. The
      antagonistic effect of 15-LO1 is mediated by the Pro(564) /hydroxylation/26S
      proteasome system, while both the enzymatic activity and the intracellular
      membrane-binding function of 15-LO1 appear to contribute to HIF-1alpha
      suppression. Our findings provide a novel mechanism for HIF-1alpha regulation, in
      which oxygen-dependent HIF-1 activity is modulated by an oxygen-insensitive lipid
      metabolic enzyme.

PMID- 24668886
TI  - Native protein mapping and visualization of protein interactions in the area of
      human plasma high-density lipoprotein by combining nondenaturing micro 2DE and
      quantitative LC-MS/MS.
AB  - A human plasma sample was subjected to nondenaturing micro 2DE and a gel area (5
      mm * 18 mm) that includes high-density lipoprotein (HDL) was cut into 1 mm * 1 mm
      squares, then the proteins in the 90 gel pieces were analyzed by quantitative LC
      MS/MS. Grid-cutting of the gel was employed to; (i) ensure the total analysis of
      the proteins in the area, (ii) standardize the conditions of analysis by LC
      MS/MS, (iii) reconstruct the protein distribution patterns from the quantity
      data. Totally 154 proteins were assigned in the 90 gel pieces and the quantity
      distribution of each was reconstructed as a color density pattern (a native
      protein map). The map of apolipoprotein (Apo) A-I showed a wide apparent mass
      distribution characteristic to HDL and was compared with the maps of the other
      153 proteins. Eleven proteins showed maps of wide distribution that overlapped
      with the map of Apo A-I, and all have been reported to be the components of HDL.
      Further, seven minor proteins associated with HDL were detected at the gel
      positions of high Apo A-I quantity. These results for the first time visualized
      the localization of HDL apolipoproteins on a nondenaturing 2DE gel and strongly
      suggested their interactions.

PMID- 24668887
TI  - Hyperphosphatemic familial tumoral calcinosis: response to acetazolamide and
      postulated mechanisms.
AB  - Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by enhanced
      renal phosphate absorption, hyperphosphatemia, and tumor-like extraosseous
      calcifications due to inactivating mutations in FGF23 or associated proteins.
      Surgical excision is needed when low phosphate diet and phosphate binders are
      ineffective. Sporadic reports have supported acetazolamide use. We report on a 7
      year-old African American boy who presented with severe HFTC requiring numerous
      surgical excisions. Tumors continued to appear and others reoccurred despite
      phosphate restriction and sevelamer carbonate. At the age of 9.5 years,
      acetazolamide (40 mg/kg/day) was added and resulted in mild metabolic acidosis
      (bicarbonate 25.3 mEq/L vs. 21.4 mEq/L, P < 0.001; serum pH 7.38 vs. 7.31, P =
      0.013, pre- and post-acetazolamide, respectively) but no change in tubular
      reabsorption of phosphate (TRP) (96.9% vs. 95.9%, P = 0.34) or serum phosphate
      (6.6 mg/dl vs. 6.9 mg/dl, P = 0.52 pre- and post-acetazolamide, respectively).
      Following the initiation of acetazolamide therapy, the patient experienced
      significant improvement in disease course as indicated by resolution of localized
      bone pain, cessation of tumor formation, and no tumor recurrence. Despite mild
      metabolic acidosis, our patient had improved linear growth and did not develop
      any other side effects related to therapy. Intact FGF23 remained abnormally low
      throughout disease course, while C-terminal FGF23 increased with acetazolamide.
      We conclude that acetazolamide can control severe HFTC by inducing mild metabolic
      acidosis despite no change in serum phosphate or TRP. This effect may be exerted
      though improved calcium-phosphate complex solubility and increased FGF23 locally.

PMID- 24668889
TI  - Coaxing solid-state phosphorescence from tellurophenes.
AB  - The synthesis of the first examples of tellurophenes exhibiting phosphorescence
      in the solid state and under ambient conditions (room temperature and in air) is
      reported. Each of these main-group-element-based emitters feature
      pinacolboronates (BPin) as ring-appended side groups. The nature of the
      luminescence observed was also investigated using computational methods. 

PMID- 24668888
TI  - Development of intrinsically photoluminescent and photostable polylactones.
AB  - A method of introducing intrinsically photo luminescent properties to
      biodegradable polymer is introduced, exemplified by the synthesis of
      intrinsically photoluminescent polylactones that enable non-invasive monitoring
      and tracking of material degradation in vivo in realtime, as well as the
      formation of theranostic nanoparticles for cancer imaging and drug delivery. 

PMID- 24668890
TI  - Thiazole-based gamma-building blocks as reverse-turn mimetic to design a
      gramicidin S analogue: conformational and biological evaluation.
AB  - This paper describes the ability of a new class of heterocyclic gamma-amino acids
      named ATCs (4-amino(methyl)-1,3-thiazole-5-carboxylic acids) to induce turns when
      included in a tetrapeptide template. Both hybrid Ac-Val-(R or S)-ATC-Ile-Ala-NH2
      sequences were synthesized and their conformations were studied by circular
      dichroism, NMR spectroscopy, MD simulations, and DFT calculations. It was
      demonstrated that the ATCs induced highly stable C9 pseudocycles in both
      compounds promoting a twist turn and a reverse turn conformation depending on
      their absolute configurations. As a proof of concept, a bioactive analogue of
      gramicidin S was successfully designed using an ATC building block as a turn
      inducer. The NMR solution structure of the analogue adopted an antiparallel beta
      pleated sheet conformation similar to that of the natural compound. The hybrid
      alpha,gamma-cyclopeptide exhibited significant reduced haemotoxicity compared to
      gramicidin S, while maintaining strong antibacterial activity. 

PMID- 24668891
TI  - Co-delivery of doxorubicin and siRNA with reduction and pH dually sensitive
      nanocarrier for synergistic cancer therapy.
AB  - Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co
      delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to
      silence drug resistant genes during the course of cancer chemotherapy for an
      improved chemotherapeutic effect. This study aims at effective co-delivery of
      siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG
      PAsp(AED)-PDPA consisting of pH-sensitive poly(2-(diisopropyl amino)ethyl
      methacrylate) (PDPA), reduction-sensitive poly(N-(2,2'-dithiobis(ethylamine))
      aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and
      assembled into a core-shell structural micelle which encapsulated doxorubicin
      (DOX) in its pH-sensitive core and the siRNA-targeting anti-apoptosis BCL-2 gene
      (BCL-2 siRNA) in a reduction-sensitive interlayer. At the optimized size and zeta
      potential, the nanocarriers loaded with DOX and BCL-2 siRNA may effectively
      accumulate in the tumor site via blood circulation. Moreover, the dual stimuli
      responsive design of micellar carriers allows microenviroment-specific rapid
      release of both DOX and BCL-2 siRNA inside acidic lysosomes with enriched
      reducing agent, glutathione (GSH, up to 10 mM). Consequently, the expression of
      anti-apoptotic BCL-2 protein induced by DOX treatment is significantly down
      regulated, which results in synergistically enhanced apoptosis of human ovarian
      cancer SKOV-3 cells and thus dramatically inhibited tumor growth.

PMID- 24668892
TI  - Canadian court decision challenges new rules on medical marijuana.

PMID- 24668893
TI  - Saving two birds with one stone: using active substance avian acute toxicity data
      to predict formulated plant protection product toxicity.
AB  - Environmental safety assessments for exposure of birds require the provision of
      acute avian toxicity data for both the pesticidal active substance and formulated
      products. As an example, testing on the formulated product is waived in Europe
      using an assessment of data for the constituent active substance(s). This is
      often not the case globally, because some countries require acute toxicity tests
      with every formulated product, thereby triggering animal welfare concerns through
      unnecessary testing. A database of 383 formulated products was compiled from
      acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or
      Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the
      383 formulated products studied, 159 contained only active substances considered
      functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of
      these, 97% had formulated product LD50 values of >2000 mg formulated product/kg
      (limit dose), indicating that no new information was obtained in the formulated
      product study. Furthermore, defined (point estimated) LD50 values for formulated
      products were compared with LD50 values predicted from toxicity of the active
      substance(s). This demonstrated that predicted LD50 values were within 2-fold and
      5-fold of the measured formulated product LD50 values in 90% and 98% of cases,
      respectively. This analysis demonstrates that avian acute toxicity testing of
      formulated products is largely unnecessary and should not be routinely required
      to assess avian acute toxicity. In particular, when active substances are known
      to be functionally nontoxic, further formulated product testing adds no further
      information and unnecessarily increases bird usage in testing. A further analysis
      highlights the fact that significant reductions (61% in this dataset) could be
      achieved by using a sequential testing design (Organisation for Economic Co
      operation and Development test guideline 223), as opposed to established single
      stage designs.

PMID- 24668894
TI  - Total synthesis of syringolin A and improvement of its biological activity.
AB  - The development process for syringolin A analogues having improved proteasome
      inhibitory and antitumor activity is described. The strategy was to first
      establish a convergent synthesis of syringolin A using a rare intramolecular Ugi
      three-component reaction in the last stage of the synthesis, so as to gain access
      toa set of structure-based analogues. The inhibitory activity of chymotrypsin
      like activity of 20S proteasome was largely improved by targeting the S3 subsite
      of the beta5 subunit. Cytotoxic activity was also improved by installing the
      membrane-permeable substituent. These biological properties are comparable to
      those of bortezomib, a clinically used first-line proteasome inhibitor. 

PMID- 24668895
TI  - Comparison of HER2 expression between primary colorectal cancer and their
      corresponding metastases.
AB  - The aim of this study was to compare human epidermal growth factor 2 (HER2)
      status in primary colorectal cancer and paired liver or lung metastasis. Gene
      amplification of HER2 has been intensively evaluated in contemporary oncology,
      especially in breast and stomach cancer. The knowledge of HER2 status in primary
      and metastatic sites may be of potential value for therapeutic decision making in
      metastatic colon cancer. The HER2 status was assessed by fluorescence in situ
      hybridization (FISH) and immunohistochemistry (IHC) in 94 colorectal cancer with
      corresponding liver or lung metastases. HER2 amplification was present in 19 of
      the 188 (10.1%) of both primary and metastases combined. Four (4.6%) patients
      showed HER2 amplification in the metastasis and 10 (10.6%) patients showed HER2
      amplification in the primary tumor. In 14 cases (14.8%), the HER2 status of the
      primary lesions was different from that of the associated metastases. The
      presence of HER2 overexpression in KRAS mutant colon cancer was found in 5.3%. No
      relationship was found between HER2 expression and KRAS status (P = 0.486). The
      evidence of HER2 positive metastatic lesion and primary colorectal cancer suggest
      that HER2 assessment might be considered in selected cases when this may help
      change the therapeutic decision.

PMID- 24668896
TI  - Recent advances in low-cost microfluidic platforms for diagnostic applications.
AB  - The use of inexpensive materials and cost-effective manufacturing processes for
      mass production of microfluidic devices is very attractive and has spurred a
      variety of approaches. Such devices are particularly suited for diagnostic
      applications in limited resource settings. This review describes the recent and
      remarkable advances in the use of low-cost substrates for the development of
      microfluidic devices for diagnostics and clinical assays. Thus, a plethora of new
      and improved fabrication methods, designs, capabilities, detections, and
      applications of microfluidic devices fabricated with paper, plastic, and threads
      are covered. 

PMID- 24668897
TI  - De novo duplication of 17p13.1-p13.2 in a patient with intellectual disability
      and obesity.
AB  - 17p13.1 Deletion encompassing TP53 has been described as a syndrome characterized
      by intellectual disability and dysmorphic features. Only one case with a 17p13.1
      duplication encompassing TP53 has been reported in a patient with intellectual
      disability, seizures, obesity, and diabetes mellitus. Here, we present a patient
      with a 17p13.1 duplication who exhibited obesity and intellectual disability,
      similar to the previous report. The 9-year-old proposita was referred for the
      evaluation of intellectual disability and obesity. She also exhibited insulin
      resistance and liver dysfunction. She had wide palpebral fissures, upturned
      nostrils, a long mandible, short and slender fingers, and skin hyperpigmentation.
      Array comparative genomic hybridization (array CGH) detected a 3.2 Mb duplication
      of 17p13.1-p13.2 encompassing TP53, FXR2, NLGN2, and SLC2A4, which encodes the
      insulin-responsive glucose transporter 4 (GLUT4) associated with insulin
      stimulated glucose uptake in adipocytes and muscle. We suggest that 17p13.1
      duplication may represent a clinically recognizable condition characterized
      partially by a characteristic facial phenotype, developmental delay, and obesity.

PMID- 24668899
TI  - Impact of the mechanical stress on switching characteristics of electrochemical
      resistive memory.

PMID- 24668898
TI  - Point decoration of silicon nanowires: an approach toward single-molecule
      electrical detection.
AB  - Probing interactions of biological systems at the molecular level is of great
      importance to fundamental biology, diagnosis, and drug discovery. A rational
      bioassay design of lithographically integrating individual point scattering sites
      into electrical circuits is capable of realizing real-time, label-free
      biodetection of influenza H1N1 viruses with single-molecule sensitivity and high
      selectivity by using silicon nanowires as local reporters in combination with
      microfluidics. This nanocircuit-based architecture is complementary to more
      conventional optical techniques, but has the advantages of no bleaching problems
      and no fluorescent labeling. These advantages offer a promising platform for
      exploring dynamics of stochastic processes in biological systems and gaining
      information from genomics to proteomics to improve accurate molecular and even
      point-of-care clinical diagnosis. 

PMID- 24668900
TI  - Structural diversity of bulky graphene materials.
AB  - The unique two-dimensional (2D) structure and chemical properties of graphene and
      its derivatives make it a distinctive nanoscale building block for constructing
      novel bulky architectures with different dimensions, such as 1D fibers, 2D films
      and 3D architectures. These bulky graphene materials, depending on the manner in
      which graphene sheets are assembled, show a variety of fascinating features that
      cannot be achieved from individual graphene sheet or conventional materials.
      Thus, over the past several years, considerable effort has been expended in
      fabricating various structures of bulky graphene materials and developing their
      corresponding applications. Here, we present a broad and comprehensive overview
      of the recent developments in expanding the structural diversity of bulky
      graphene materials and their applications in energy storage and conversion,
      composites, environmental remediation, etc. Finally, prospects and further
      developments in this exciting field of bulky graphene materials are also
      suggested. 

PMID- 24668901
TI  - An inexpensive, temporally integrated system for monitoring occurrence and
      biological effects of aquatic contaminants in the field.
AB  - Assessment of potential risks of complex contaminant mixtures in the environment
      requires integrated chemical and biological approaches. In support of the US
      Great Lakes Restoration Initiative, the US Environmental Protection Agency lab in
      Duluth, MN, is developing these types of methods for assessing possible risks of
      aquatic contaminants in near-shore Great Lakes (USA) sites. One component
      involves an exposure system for caged fathead minnow (Pimephales promelas) adults
      suitable for the wide range of habitat and deployment situations encountered in
      and around the Great Lakes. To complement the fish exposure system, the authors
      developed an automated device for collection of composite water samples that
      could be simultaneously deployed with the cages and reflect a temporally
      integrated exposure of the animals. The present study describes methodological
      details of the design, construction, and deployment of a flexible yet
      comparatively inexpensive (<600 USD) caged-fish/autosampler system. The utility
      and performance of the system were demonstrated with data collected from
      deployments at several Great Lakes sites. For example, over 3 field seasons, only
      2 of 130 deployed cages were lost, and approximately 99% of successfully deployed
      adult fish were recovered after exposures of 4 d or longer. A number of
      molecular, biochemical, and apical endpoints were successfully measured in
      recovered animals, changes in which reflected known characteristics of the study
      sites (e.g., upregulation of hepatic genes involved in xenobiotic metabolism in
      fish held in the vicinity of wastewater treatment plants). The automated
      composite samplers proved robust with regard to successful water collection (>95%
      of deployed units in the latest field season), and low within- and among-unit
      variations were found relative to programmed collection volumes. Overall, the
      test system has excellent potential for integrated chemical-biological monitoring
      of contaminants in a variety of field settings.

PMID- 24668904
TI  - Has cognitive behavioural therapy for psychosis been oversold?

PMID- 24668905
TI  - Novel triblock co-polymer nanofibre system as an alternative support for
      embryonic stem cells growth and pluripotency.
AB  - Conventionally, embryonic stem cells (ESCs) are cultured on gelatin or over a
      mitotically inactivated monolayer of mouse embryonic fibroblasts (MEFsi).
      Considering the lack of versatile, non-animal-derived and inexpensive materials
      for that purpose, we aimed to find a biomaterial able to support ESC growth in a
      pluripotent state that avoids the need for laborious and time-consuming MEFsi
      culture in parallel with mouse ESC (mESC) culture. Undifferentiated mESCs were
      cultured in a new nanofibre material designed for ESC culture, which is based on
      the self-assembly of a triblock co-polymer, poly(ethyleneglycol-beta
      trimethylsilyl methacrylate-beta-methacrylic acid), conjugated with the peptide
      glycine-arginine-glycine-aspartate-serine, to evaluate its potential application
      in ESC research. The morphology, proliferation, viability, pluripotency and
      differentiation potential of mESCs were assessed. Compared to conventional stem
      cell culture methodologies, the nanofibres promoted a higher increase in mESCs
      number, enhanced pluripotency and were able to support differentiation after long
      term culture. This newly developed synthetic system allows the elimination of
      animal-derived matrices and provides an economic method of ESC culture, made of a
      complex network of nanofibres in a scale similar to native extracellular
      matrices, where the functional properties of the cells can be observed and
      manipulated. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668906
TI  - Cross-resistance, the stability of acetamiprid resistance and its effect on the
      biological parameters of cotton mealybug, Phenacoccus solenopsis (Homoptera:
      Pseudococcidae), in Pakistan.
AB  - BACKGROUND: Acetamiprid is a neonicotinoid insecticide that is effective against
      both soil and plant insects, including insects of the orders Lepidoptera,
      Coleoptera, Homoptera and Thysanoptera. In order to estimate the effects
      associated with insecticide exposure and devise better pest management tactics, a
      field population of Phenacoccus solenopsis was exposed to acetamiprid in the
      laboratory. Subsequently, cross-resistance and the effects of acetamiprid on the
      biological parameters of P. solenopsis were investigated. RESULTS: Following five
      rounds of selection with acetamiprid, P. solenopsis developed a 315-fold greater
      resistance to this chemical compared with an unexposed control population. The
      selected population also demonstrated very high to moderate cross-resistance to
      other tested insecticides. Furthermore, acetamiprid resistance remained unstable
      when the acetamiprid-selected population was not exposed for a further five
      generations. The acetamiprid-selected population had a relative fitness of 0.22,
      with significantly lower survival rate, pupal weight, fecundity, percentage
      hatching, net reproductive rate, intrinsic rate of natural increase, biotic
      potential and mean relative growth rate, with prolonged male and female nymphal
      duration, developmental time from egg to female adult and male and female
      longevity compared with the control population. CONCLUSION: P. solenopsis
      biological parameters are greatly affected by acetamiprid, and it is of
      significant cost for the insects to counter these effects. This study will be a
      valuable source of information for further understanding of acetamiprid
      resistance and for assisting the development of resistance management programmes.

PMID- 24668903
TI  - Phosphorylcholine-coated semiconducting polymer nanoparticles as rapid and
      efficient labeling agents for in vivo cell tracking.
AB  - Despite the pressing need to noninvasively monitor transplanted cells in vivo
      with fluorescence imaging, desirable fluorescent agents with rapid labeling
      capability, durable brightness, and ideal biocompatibility remain lacking. Here,
      phosphorylcholine-coated near-infrared (NIR) fluorescent semiconducting polymer
      nanoparticles (SPNs) are reported as a new class of rapid, efficient, and
      cytocompatible labeling nanoagents for in vivo cell tracking. The
      phosphorylcholine coating results in efficient and rapid endocytosis and allows
      the SPN to enter cells within 0.5 h in complete culture medium apparently
      independent of the cell type, while its NIR fluorescence leads to a tissue
      penetration depth of 0.5 cm. In comparison to quantum dots and Cy5.5, the SPN is
      tolerant to physiologically ubiquitous reactive oxygen species (ROS), resulting
      in durable fluorescence both in vitro and in vivo. These desirable physical and
      physiological properties of the SPN permit cell tracking of human renal cell
      carcinoma (RCC) cells in living mice at a lower limit of detection of 10 000
      cells with no obvious alteration of cell phenotype after 12 d. SPNs thus can
      provide unique opportunities for optimizing cellular therapy and deciphering
      pathological processes as a cell tracking label. 

PMID- 24668907
TI  - Maternal smoking, xenobiotic metabolizing enzyme gene variants, and gastroschisis
      risk.
AB  - Maternal smoking during pregnancy is one proposed risk factor for gastroschisis,
      but reported associations have been modest, suggesting that differences in
      genetic susceptibility might play a role. We included 108 non-Hispanic white and
      62 Hispanic families who had infants with gastroschisis, and 1,147 non-Hispanic
      white and 337 Hispanic families who had liveborn infants with no major structural
      birth defects (controls) in these analyses. DNA was extracted from buccal cells
      collected from infants and mothers, and information on periconceptional smoking
      history was obtained from maternal interviews, as part of the National Birth
      Defects Prevention Study. We analyzed five polymorphisms in three genes that code
      for enzymes involved in metabolism of some cigarette smoke constituents (CYP1A1,
      CYP1A2, and NAT2). Logistic regression models were used to estimate odds ratios
      (ORs) and 95% confidence intervals (CIs) independently for maternal smoking and
      maternal and infant gene variants, and to assess joint associations of maternal
      smoking and maternal or infant gene variants with gastroschisis. In analyses
      adjusted for maternal age at delivery and stratified by maternal race-ethnicity,
      we identified three suggestive associations among 30 potential associations with
      sufficient numbers to calculate ORs: CYP1A1*2A for non-Hispanic white mothers who
      smoked periconceptionally (aOR = 0.38, 95% CI 0.15-0.98), and NAT2*6 for Hispanic
      non-smoking mothers (aOR = 2.17, 95% CI 1.12-4.19) and their infants (aOR = 2.11,
      95% CI 1.00-4.48). This analysis does not support the occurrence of effect
      modification between periconceptional maternal smoking and most of the xenobiotic
      metabolizing enzyme gene variants assessed.

PMID- 24668910
TI  - Silver(I)-catalyzed hydroazidation of ethynyl carbinols: synthesis of 2
      azidoallyl alcohols.
AB  - The hydroazidation of alkynes is the most straightforward pathway to
      synthetically useful vinyl azides. However, a general hydroazidation of alkynes
      remains elusive. Herein, a chemo- and regioselective transformation of ethynyl
      carbinols into vinyl azides is described. This reaction produces a wide variety
      of 2-azidoallyl alcohols with high efficiency and in good to excellent yields.
      These compounds constitute a new class of densely functionalized synthetic
      intermediates. Their synthetic potential has been demonstrated by further
      transformations into NH aziridines. The mechanistic aspects of the reaction will
      attract the attention of chemists working on alkyne chemistry and silver
      catalysis. The findings that are described in this paper represent significant
      advances in the regioselective hydroelementation of alkynes and open a new
      reaction manifold for exploitation.

PMID- 24668908
TI  - High-resolution mapping defines the cooperative architecture of Polycomb response
      elements.
AB  - Polycomb-mediated chromatin repression modulates gene expression during
      development in metazoans. Binding of multiple sequence-specific factors at
      discrete Polycomb response elements (PREs) is thought to recruit repressive
      complexes that spread across an extended chromatin domain. To dissect the
      structure of PREs, we applied high-resolution mapping of nonhistone chromatin
      proteins in native chromatin of Drosophila cells. Analysis of occupied sites
      reveal interactions between transcription factors that stabilize Polycomb
      anchoring to DNA, and implicate the general transcription factor ADF1 as a novel
      PRE component. By comparing two Drosophila cell lines with differential chromatin
      states, we provide evidence that repression is accomplished by enhanced Polycomb
      recruitment both to PREs and to target promoters of repressed genes. These
      results suggest that the stability of multifactor complexes at promoters and
      regulatory elements is a crucial aspect of developmentally regulated gene
      expression. 

PMID- 24668909
TI  - Widespread context dependency of microRNA-mediated regulation.
AB  - Gene expression is regulated in a context-dependent, cell-type-specific manner.
      Condition-specific transcription is dependent on the presence of transcription
      factors (TFs) that can activate or inhibit its target genes (global context).
      Additional factors, such as chromatin structure, histone, or DNA modifications,
      also influence the activity of individual target genes (individual context). The
      role of the global and individual context for post-transcriptional regulation has
      not systematically been investigated on a large scale and is poorly understood.
      Here we show that global and individual context dependency is a pervasive feature
      of microRNA-mediated regulation. Our comprehensive and highly consistent data set
      from several high-throughput technologies (PAR-CLIP, RIP-chip, 4sU-tagging, and
      SILAC) provides strong evidence that context-dependent microRNA target sites
      (CDTS) are as frequent and functionally relevant as constitutive target sites
      (CTS). Furthermore, we found the global context to be insufficient to explain the
      CDTS, and that flanking sequence motifs provide individual context that is an
      equally important factor. Our results demonstrate that, similar to TF-mediated
      regulation, global and individual context dependency are prevalent in microRNA
      mediated gene regulation, implying a much more complex post-transcriptional
      regulatory network than is currently known. The necessary tools to unravel post
      transcriptional regulations and mechanisms need to be much more involved, and
      much more data will be needed for particular cell types and cellular conditions
      in order to understand microRNA-mediated regulation and the context-dependent
      post-transcriptional regulatory network. 

PMID- 24668913
TI  - Sign inversion of the spontaneous polarization in a "de Vries"-type ferroelectric
      liquid crystal.
AB  - In contrast to common ferroelectric smectic C* liquid crystals, the siloxane
      terminated smectic mesogen E6 is characterized by an unusual temperature
      variation of the spontaneous polarization. The polarization starts to grow from
      nearly zero despite the first-order SmA*-SmC* transition, and increases faster
      than linearly over a large temperature interval while the tilt angle rapidly
      saturates. To study this behavior in more detail, binary mixtures of different
      concentrations of E6 in the achiral SmC material C8Cl, which has a similar
      chemical structure, were investigated. Surprisingly, all mixtures show a
      temperature dependent polarization sign inversion, which shifts towards the SmC*
      SmA* transition with increasing E6 concentration. For the pure E6 the inversion
      temperature meets the SmA*-SmC* phase transition temperature. In a second binary
      mixture with E6 and a conventional material C9-2PhP we found out, that the
      dependence of the inversion temperature on the concentration of E6 changes
      qualitatively when the nanosegregation is partially destroyed. A molecular theory
      of the polarization sign inversion in smectics C* with strong polar
      intermolecular interactions is developed which enables one to explain the
      concentration dependence of the inversion temperature in both mixtures. 

PMID- 24668912
TI  - Roles of the spinal glutamatergic pathway activated through alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid (AMPA) receptors and its interactions with
      spinal noradrenergic and serotonergic pathways in the rat urethral continence
      mechanisms.
AB  - AIMS: To investigate the role of the glutamatergic pathway and its relationship
      to noradrenergic and serotonergic pathways in modulation of the urethral
      continence reflex during sneezing in rats. METHODS: In female Sprague-Dawley rats
      under urethane anesthesia, the effects of an alpha-amino-3-hydroxy-5-meth
      ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a
      norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5
      HT)]2B/2C agonist on the amplitude of urethral responses during sneezing (AURS),
      urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP)
      were investigated. RESULTS: Intrathecal application (i.t.) of NBQX disodium salt
      (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately
      60% without affecting UBP and caused stress urinary incontinence (SUI) during
      sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake
      inhibitor, and mCPP (i.t.), a 5-HT(2B/2C), agonist increased AURS, and NBQX
      (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.),
      whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of
      NBQX (i.t.). CONCLUSION: These results indicate that the glutamatergic pathway
      acting through AMPA receptors plays a crucial role on the active urethral closure
      reflex during sneezing at the spinal level, and noradrenergic and serotonergic
      pathways modulate the reflex via the spinal glutamatergic system in rats.

PMID- 24668911
TI  - Guiding stem cell differentiation into oligodendrocytes using graphene-nanofiber
      hybrid scaffolds.

PMID- 24668914
TI  - Neutralized nanoparticle composed of SS-cleavable and pH-activated lipid-like
      material as a long-lasting and liver-specific gene delivery system.
AB  - Charge-neutralized lipid envelope-type nanoparticles formed with SS-cleavable and
      pH-activated lipid-like materials (ssPalm) accumulate rapidly in the liver
      without forming aggregates in the blood circulation, and result in a liver
      specific gene expression for a long duration (>2 weeks) with neither
      immunological responses nor hepatotoxicity after intraveneous administration,
      when it carries pDNA free from CpG-motifs. 

PMID- 24668915
TI  - Evidence for annular pancreas as an associated anomaly in the VATER/VACTERL
      association and investigation of the gene encoding pancreas specific
      transcription factor 1A as a candidate gene.

PMID- 24668916
TI  - Evaluation of the time-concentration-mortality responses of Plutella xylostella
      larvae to the interaction of Isaria fumosorosea with the insecticides beta
      cypermethrin and Bacillus thuringiensis.
AB  - BACKGROUND: Entomopathogenic fungi are potential candidates for controlling
      Plutella xylostella, a cosmopolitan pest of crucifers. In this study, bioassays
      were conducted to evaluate the interaction between Isaria fumosorosea and
      sublethal doses of two insecticides, beta-cypermethrin and Bacillus
      thuringiensis, against P. xylostella. RESULTS: Data of each assay were in good
      agreement with the time-concentration-mortality model, indicating a strong
      dependence of the fungus and insecticide interaction on both concentration and
      post-exposure time. Using beta-cypermethrin 58-116 ug mL(-1) or B. thuringiensis
      222.5-890 ug mL(-1) with the fungus significantly enhanced fungal efficacy. The
      LC50 values of the fungus declined over a 1-7 day period after exposure, and the
      LT50 values decreased with increasing concentration. Based on LC50 or LC90
      estimates, synergism between the fungus and beta-cypermethrin resulted in a 2.7
      28.3-fold reduction in LC50 values and a 12.1-19.6-fold reduction in LC90 values,
      while synergism of the fungus with B. thuringiensis led to a 2.4-385.0-fold
      reduction in LC50 values and a 4.4-151.7-fold reduction in LC90 values.
      CONCLUSION: Results show that sublethal doses of B. thuringiensis and beta
      cypermethrin can synergise I. fumosorosea activity on P. xylostella, suggesting
      that combination of I. fumosorosea with the two insecticides might offer an
      integrated approach to controlling P. xylostella in practice. (c) 2014 Society of
      Chemical Industry.

PMID- 24668917
TI  - Separation of photoactive conformers based on hindered diarylethenes: efficient
      modulation in photocyclization quantum yields.
AB  - Endowing both solvent independency and excellent thermal bistability, the
      benzobis(thiadiazole)-bridged diarylethene system provides an efficient approach
      to realize extremely high photocyclization quantum yields (Phio-c , up to 90.6 %)
      by both separating completely pure anti-parallel conformer and suppressing
      intramolecular charge transfer (ICT). 

PMID- 24668918
TI  - Contribution of cytosine-containing cyclobutane dimers to DNA damage produced by
      photosensitized triplet-triplet energy transfer.
AB  - Mutagenic cyclobutane pyrimidine dimers (CPDs) can be induced in DNA through
      either direct excitation or photosensitized triplet-triplet energy transfer
      (TTET). In the latter pathway, thymines are expected to receive the excitation
      energy from the photosensitizer and react with adjacent pyrimidines. By using
      state-of-the art analytical tools, we provide herein additional information on
      the formation of cytosine-containing CPDs. We thus determined the yield of all
      possible CPDs upon TTET in a series of natural DNAs with various base
      compositions. We show that the distribution of CPDs cannot be explained only by
      excitation of individual thymines. We propose that the mechanism for TTET
      involves at least dinucleotides as the minimal targets. The observation of the
      formation of cytosine-cytosine CPDs also suggests that additional pathways are
      involved in this photosensitized reaction. 

PMID- 24668919
TI  - Reduction of epoxidized vegetable oils: a novel method to prepare bio-based
      polyols for polyurethanes.
AB  - A novel method, epoxidation/reduction of vegetable oils, is developed to prepare
      bio-based polyols for the manufacture of polyurethanes (PUs). These polyols are
      synthesized from castor oil (CO), epoxidized soybean oil, and epoxidized linseed
      oil and their molecular structures are characterized. They are used to prepare a
      variety of PUs, and their thermomechanical properties are compared to those of PU
      made with petroleum-based polyol (P-450). It is shown that PUs made with polyols
      from soybean and linseed oil exhibit higher glass transition temperatures,
      tensile strength, and Young's modulus and PU made with polyol from CO exhibits
      higher elongation at break and toughness than PU made with P-450. However, PU
      made with P-450 displays better thermal resistance because of tri-ester structure
      and terminal functional groups. The method provides a versatile way to prepare
      bio-polyols from vegetable oils, and it is expected to partially or completely
      replace petroleum-based polyols in PUs manufacture. 

PMID- 24668921
TI  - Sample preparation of energy materials for X-ray nanotomography with
      micromanipulation.
AB  - X-ray nanotomography presents an unprecedented opportunity to study energy
      storage/conversion materials at nanometer scales in three dimensions, with both
      elemental and chemical sensitivity. A critical step in obtaining high-quality X
      ray nanotomography data is reliable sample preparation to ensure that the entire
      sample fits within the field of view of the X-ray microscope. Although focused
      ion-beam lift-out has previously been used for large sample (few to tens of
      microns) preparation, a difficult undercut and lift-out procedure results in a
      time-consuming sample preparation process. Herein, we propose a much simpler and
      direct sample preparation method to resolve the issues that block the view of the
      sample base after milling and during the lift-out process. This method is applied
      on a solid-oxide fuel cell and a lithium-ion battery electrode, before numerous
      critical 3D morphological parameters are extracted, which are highly relevant to
      their electrochemical performance. A broad application of this method for
      microstructure study with X-ray nanotomography is discussed and presented. 

PMID- 24668920
TI  - Soft robotic concepts in catheter design: an on-demand fouling-release urinary
      catheter.
AB  - Infectious biofilms are problematic in many healthcare-related devices and are
      especially challenging and ubiquitous in urinary catheters. This report presents
      an on-demand fouling-release methodology to mechanically disrupt and remove
      biofilms, and proposes this method for the active removal of infectious biofilms
      from the previously inaccessible main drainage lumen of urinary catheters. Mature
      Proteus mirabilis crystalline biofilms detach from silicone elastomer substrates
      upon application of strain to the substrate, and increasing the strain rate
      increases biofilm detachment. The study presents a quantitative relationship
      between applied strain rate and biofilm debonding through an analysis of biofilm
      segment length and the driving force for debonding. Based on this mechanism,
      hydraulic and pneumatic elastomer actuation is used to achieve surface strain
      selectively within the lumen of prototypes of sections of a fouling-release
      urinary catheter. Proof-of-concept prototypes of sections of active, fouling
      release catheters are constructed using techniques typical to soft robotics
      including 3D printing and replica molding, and those prototypes demonstrate
      release of mature P. mirabilis crystalline biofilms (e.g., ~90%) from strained
      surfaces. These results provide a basis for the development of a new urinary
      catheter technology in which infectious biofilms are effectively managed through
      new methods that are entirely complementary to existing approaches. 

PMID- 24668922
TI  - Novel FBN1 gene mutation and maternal germinal mosaicism as the cause of neonatal
      form of Marfan syndrome.
AB  - Marfan syndrome (MFS) is an autosomal dominant disorder caused by mutations in
      the fibrillin 1 gene (FBN1). Neonatal form of MFS is rare and is associated with
      severe phenotype and a poor prognosis. We report on a newborn girl with neonatal
      MFS who displayed cyanosis and dyspnea on the first day of life. The main
      clinical features included mitral and tricuspid valve insufficiency, aortic root
      dilatation, arachnodactyly, and loose skin. Despite the presence of severe and
      inoperable heart anomalies, the girl was quite stable on symptomatic treatment
      and lived up to the 7th month of age when she died due to cardiorespiratory
      failure. Molecular-genetic studies revealed a novel intronic c.4211-32_-13del
      mutation in the FBN1 gene. Subsequent in vitro splicing analysis showed this
      mutation led to exon 35 skipping, presumably resulting in a deletion of 42 amino
      acids (p.Leu1405_Asp1446del). Interestingly, this mutation is localized outside
      the region of exons 24-32, whose mutation is responsible for the substantial
      majority of cases of neonatal MFS. Although the family history of MFS was
      negative, the subsequent molecular genetic examination documented a mosaicism of
      the same mutation in the maternal blood cells (10-25% of genomic DNA) and the
      detailed clinical examination showed unilateral lens ectopy.

PMID- 24668923
TI  - Scarring, stem cells, scaffolds and skin repair.
AB  - The treatment of full thickness skin loss, which can be extensive in the case of
      large burns, continues to represent a challenging clinical entity. This is due to
      an on-going inability to produce a suitable tissue engineered substrate that can
      satisfactorily replicate the epidermal and dermal in vivo niches to fulfil both
      aesthetic and functional demands. The current gold standard treatment of
      autologous skin grafting is inadequate because of poor textural durability,
      scarring and associated contracture, and because of a paucity of donor sites in
      larger burns. Tissue engineering has seen exponential growth in recent years with
      a number of 'off-the-shelf' dermal and epidermal substitutes now available. Each
      has its own limitations. In this review, we examine normal wound repair in
      relation to stem/progenitor cells that are intimately involved in this process
      within the dermal niche. Endothelial precursors, in particular, are examined
      closely and their phenotype, morphology and enrichment from multiple sources are
      described in an attempt to provide some clarity regarding the controversy
      surrounding their classification and role in vasculogenesis. We also review the
      role of the next generation of cellularized scaffolds and smart biomaterials that
      attempt to improve the revascularisation of artificial grafts, the rate of wound
      healing and the final cosmetic and functional outcome.

PMID- 24668924
TI  - Are there conserved roles for the extracellular matrix, cilia, and junctional
      complexes in left-right patterning?
AB  - Many different types of molecules have essential roles in patterning the left
      right axis and directing asymmetric morphogenesis. In particular, the
      relationship between signaling molecules and transcription factors has been
      explored extensively. Another group of proteins implicated in left-right
      patterning are components of the extracellular matrix, apical junctions, and
      cilia. These structural molecules have the potential to participate in the
      conversion of morphogenetic cues from the extracellular environment into
      morphogenetic patterning via their interactions with the actin cytoskeleton.
      Although it has been relatively easy to temporally position these proteins within
      the hierarchy of the left-right patterning pathway, it has been more difficult to
      define how they mechanistically fit into these pathways. Consequently, our
      understanding of how these factors impart patterning information to influence the
      establishment of the left-right axis remains limited. In this review, we will
      discuss those structural molecules that have been implicated in early phases of
      left-right axis development.

PMID- 24668925
TI  - Gas-phase synthesis of the benzyl radical (C(6)H(5)CH(2)).
AB  - Dicarbon (C2 ), the simplest bare carbon molecule, is ubiquitous in the
      interstellar medium and in combustion flames. A gas-phase synthesis is presented
      of the benzyl radical (C6 H5 CH2 ) by the crossed molecular beam reaction of
      dicarbon, C2 (X(1) Sigmag (+) , a(3) Piu ), with 2-methyl-1,3-butadiene
      (isoprene; C5 H8 ; X(1) A') accessing the triplet and singlet C7 H8 potential
      energy surfaces (PESs) under single collision conditions. The experimental data
      combined with ab initio and statistical calculations reveal the underlying
      reaction mechanism and chemical dynamics. On the singlet and triplet surfaces,
      the reactions involve indirect scattering dynamics and are initiated by the
      barrierless addition of dicarbon to the carbon-carbon double bond of the 2-methyl
      1,3-butadiene molecule. These initial addition complexes rearrange via multiple
      isomerization steps, leading eventually to the formation of C7 H7 radical species
      through atomic hydrogen elimination. The benzyl radical (C6 H5 CH2 ), the
      thermodynamically most stable C7 H7 isomer, is determined as the major product. 

PMID- 24668926
TI  - PEG-amine-initiated polymerization of sarcosine N-thiocarboxyanhydrides toward
      novel double-hydrophilic PEG-b-polysarcosine diblock copolymers.
AB  - Amino acid N-thiocarboxyanhydride (NTA), the thioanalog of N-carboxyanhydride
      (NCA), is much more stable than NCA against moisture and heat. The convenient
      monomer synthesis without rigorous anhydrous requirements makes the ring-opening
      polymerization of NTA a competitive alternative to prepare polypeptoid-containing
      materials with potential of large-scale production. Polysarcosines (PSars) with
      high yields (>90%) and low polydispersities (<1.2) are synthesized from sarcosine
      N-thiocarboxyanhydride (Sar-NTA) at 60  degrees C initiated by primary amines
      including poly(ethylene glycol) amine (PEG-NH2 ). The lengths of PSar segments
      are controlled by various feed ratios of Sar-NTA to initiator. PEG-b-PSar
      products, a class of novel double-hydrophilic diblock copolymers, are effective
      in stabilizing oil-in-water emulsions at nano- and microscale, which demonstrates
      promising encapsulation applications in food, cosmetics, and drug delivery. Due
      to the different solubility of PEG and PSar blocks, PEG-b-PSar copolymers form
      micelles in organic solvents with the capability to incorporate metal cations
      including Cu(2+) and Ni(2+) . 

PMID- 24668928
TI  - Increased cell seeding efficiency in bioplotted three-dimensional PEOT/PBT
      scaffolds.
AB  - In regenerative medicine studies, cell seeding efficiency is not only optimized
      by changing the chemistry of the biomaterials used as cell culture substrates,
      but also by altering scaffold geometry, culture and seeding conditions. In this
      study, the importance of seeding parameters, such as initial cell number, seeding
      volume, seeding concentration and seeding condition is shown. Human mesenchymal
      stem cells (hMSCs) were seeded into cylindrically shaped 4 * 3 mm polymeric
      scaffolds, fabricated by fused deposition modelling. The initial cell number
      ranged from 5 * 10(4) to 8 * 10(5) cells, in volumes varying from 50 ul to 400
      ul. To study the effect of seeding conditions, a dynamic system, by means of an
      agitation plate, was compared with static culture for both scaffolds placed in a
      well plate or in a confined agarose moulded well. Cell seeding efficiency
      decreased when seeded with high initial cell numbers, whereas 2 * 10(5) cells
      seemed to be an optimal initial cell number in the scaffolds used here. The
      influence of seeding volume was shown to be dependent on the initial cell number
      used. By optimizing seeding parameters for each specific culture system, a more
      efficient use of donor cells can be achieved. Copyright (c) 2013 John Wiley &
      Sons, Ltd.

PMID- 24668927
TI  - Multifunctional skin-like electronics for quantitative, clinical monitoring of
      cutaneous wound healing.
AB  - Non-invasive, biomedical devices have the potential to provide important,
      quantitative data for the assessment of skin diseases and wound healing.
      Traditional methods either rely on qualitative visual and tactile judgments of a
      professional and/or data obtained using instrumentation with forms that do not
      readily allow intimate integration with sensitive skin near a wound site. Here,
      an electronic sensor platform that can softly and reversibly laminate
      perilesionally at wounds to provide highly accurate, quantitative data of
      relevance to the management of surgical wound healing is reported. Clinical
      studies on patients using thermal sensors and actuators in fractal layouts
      provide precise time-dependent mapping of temperature and thermal conductivity of
      the skin near the wounds. Analytical and simulation results establish the
      fundamentals of the sensing modalities, the mechanics of the system, and
      strategies for optimized design. The use of this type of "epidermal" electronics
      system in a realistic clinical setting with human subjects establishes a set of
      practical procedures in disinfection, reuse, and protocols for quantitative
      measurement. The results have the potential to address important unmet needs in
      chronic wound management. 

PMID- 24668929
TI  - Mutation spectrum of COL1A1 and COL1A2 genes in Indian patients with osteogenesis
      imperfecta.
AB  - Osteogenesis imperfecta (OI) is a condition of decreased bone density with
      heterogeneous etiologies. Most of the cases are inherited in an autosomal
      dominant fashion and are caused by mutations in the COL1A1 or COL1A2 genes. Since
      these two genes are very large, there are no data about mutations in Indian
      patients with OI. We selected 35 Indian patients who were clinically diagnosed
      with OI and all exons of both the genes were sequenced. Mutations in COL1A1 (14
      cases, 6 novel) and COL1A2 (11 cases, 7 novel) were identified in 25 patients. A
      total of 55 polymorphisms were identified in both the genes with eight novel
      variants in the coding region, and nine novel variants in the non-coding regions.
      No mutation was detected in 10 patients. Six of them were from consanguineous
      families, with one or two similarly affected siblings suggesting possible
      autosomal recessive inheritance. If we exclude families with consanguinity,
      mutations were identified in 25 out of 29 families giving 86% mutation detection
      rate. Mutations in COL1A1 accounted for 56% of the cases and COL1A2 44%, which is
      similar to the reported rate worldwide.

PMID- 24668930
TI  - Characterizing the B-P stretching vibration in phosphorus-substituted phosphine
      boranes.
AB  - The experimental Raman spectra of three phosphorus-substituted phosphine boranes
      with bulky hydrocarbon substituents are presented and compared to the results of
      electronic structure computations by using the M06-2X method and the 6-311G(2df,
      2pd) basis set. Total-energy distributions (TEDs) are calculated to describe the
      degree of mixing of the dative-bond stretching vibration with other simple
      internal coordinates. This level of theory is found to accurately reproduce the B
      P stretching frequency in all three crystalline solids. The Raman spectra of five
      smaller B-P-containing molecules, including BH(3) PH(3), are also simulated at
      this level of theory and compared to previous experimental results.

PMID- 24668931
TI  - Liver transplantation and cirrhotomimetic hepatocellular carcinoma:
      classification and outcomes.
AB  - Liver transplantation has become the standard-of-care treatment for
      hepatocellular carcinoma (HCC) that falls within certain size and numerical
      criteria for patients with cirrhosis. Cirrhotomimetic (CMM) HCC is an uncommon
      growth pattern that infiltrates cirrhotic parenchyma, can become extensive in
      size, and can evade detection via radiological studies. Liver transplant outcomes
      for this type of HCC are not well reported but generally are considered to be
      poor. We wished to better describe this variant of HCC in explanted livers,
      derive a classification system for this tumor type, and assess the outcomes of
      liver transplantation for this tumor variant. All patients undergoing
      transplantation for HCC at a single center in 1996-2009 (358 patients) were
      retrospectively analyzed, and 26 patients exhibiting a CMM growth pattern were
      identified. We developed a classification system for this tumor growth pattern
      variant and determined patient and tumor-specific outcomes. We derived a
      classification schema for CMM HCC based on the tumor extent and cellular
      histopathology, with a clear cell pathology being associated with favorable
      outcomes. We noted 100.0% 3-year recurrence-free survival and 58.3% 5-year
      recurrence-free survival after transplantation for those patients with tumors
      confined to 1 lobe that had a clear cell pathology and 16.2% 3- and 5-year
      recurrence-free survival for those patients who did not meet these criteria. In
      conclusion, CMM HCC features were noted in 7% of the patients undergoing
      transplantation for HCC at our center, with favorable outcomes observed for
      inpatients with clear cell histology and growth involving less than or equal to
      50% of the liver.

PMID- 24668932
TI  - New studies of second and fourth digit ratio as a morphogenetic trait in subjects
      with congenital adrenal hyperplasia.
AB  - OBJECTIVES: Congenital adrenal hyperplasia (CAH) is a disease that occurs during
      fetal development and can lead to virilization in females or death in newborn
      males if not discovered early in life. Because of this there is a need to seek
      morphological markers in order to help diagnose the disease. In order to test the
      hypothesis that prenatal hormones can affect the sexual dimorphic pattern 2D:4D
      digit ratio in individual with CAH, the aim of this study was to compare the
      digit ratio in female and male patients with CAH and control subjects. METHODS:
      The 2D:4D ratios in both hands of 40 patients (31 females-46, XX, and 9 males-46,
      XY) were compared with the measures of control individuals without CAH (100 males
      and 100 females). RESULTS: Females with CAH showed 2D:4D ratios typical of male
      controls (0.950 and 0.947) in both hands (P < 0.001). In CAH males the left hand
      2D:4D ratio (0.983) was statistically different from that of male controls (P <
      0.05). CONCLUSIONS: These finding support the idea that sexual dimorphism in
      skeletal development in early fetal life is associated with differences between
      the exposure to androgens in males and females, and significant differences
      associated with adrenal hyperplasia. Although the effects of prenatal androgens
      on skeletal developmental are supported by numerous studies, further
      investigation is yet required to clarify the disease and establish the digit
      ratio as a biomarker for CAH.

PMID- 24668933
TI  - An atypical presentation of pulmonary air-leak syndrome and multisystem toxic
      epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is a rare and potentially fatal mucocutaneous
      condition that may affect both children and adults. TEN mortality rates vary
      greatly between both patient populations, but multisystem involvement is common.
      Management presents many challenges as there is no specific therapy for TEN, and
      patients often require the expertise of burn units. We report a child who
      survived TEN with multisystem involvement including the rare but life threatening
      occurrence of a pulmonary air-leak syndrome while also reviewing controversies
      surrounding TEN's pathophysiology, sequelae, and multidisciplinary approach to
      management.

PMID- 24668934
TI  - Transplantation of embryonic motor neurons into peripheral nerve combined with
      functional electrical stimulation restores functional muscle activity in the rat
      sciatic nerve transection model.
AB  - Reinnervation of denervated muscle by motor neurons transplanted into the
      peripheral nerve may provide the potential to excite muscles artificially with
      functional electrical stimulation (FES). Here we investigated whether
      transplantation of embryonic motor neurons into peripheral nerve combined with
      FES restored functional muscle activity in adult Fischer 344 rats after
      transection of the sciatic nerve. One week after sciatic nerve transection, cell
      culture medium containing (cell transplantation group, n = 6) or lacking
      (surgical control group, n = 6) dissociated embryonic spinal neurons was injected
      into the distal stump of the tibial and peroneal nerves. Electrophysiological and
      tissue analyses were performed in the cell transplantation and surgical control
      groups 12 weeks after transplantation, as well as a in naive control group (n =
      6) that received no surgery. In the cell transplantation group, ankle angle was
      measured during gait, with and without FES of the peroneal nerve. Ankle angle at
      mid-swing was more flexed during gait with FES (26.6 +/- 8.7 degrees ) than gait
      without FES (51.4 +/- 12.8 degrees , p = 0.011), indicating that transplantated
      motor neurons in conjunction with FES restored ankle flexion in gait, even though
      no neural connection between central nervous system and muscle was present. These
      results indicate that transplantation of embryonic motor neurons into peripheral
      nerve combined with FES can provide a novel treatment strategy for paralysed
      muscles. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668935
TI  - Hepatic venous congestion in living donor grafts in liver transplantation: is
      there an effect on hepatocellular carcinoma recurrence?
AB  - A certain degree of graft congestion in living donor liver transplantation (LDLT)
      using a right liver graft may be inevitable because of the mismatch between the
      inflow and outflow structures of the liver. The subsequent inflammatory reaction
      and rapid regeneration of the graft have been suggested as causes of tumor
      recurrence. Therefore, we investigated the influence of graft congestion on
      hepatocellular carcinoma (HCC) recurrence after LDLT. Two hundred eighty-nine
      LDLT patients for HCC within the University of California San Francisco criteria
      between November 1999 and February 2012 were investigated. Patients were assigned
      to groups on the basis of the degree of congestion (<=10% for group A and >10%
      for group B), which was determined by 3-dimensional reconstruction of
      posttransplant multidetector helical computed tomography within 2 weeks.
      Perioperative characteristics, regeneration rates after 6 months, and recurrence
      rates were compared between the groups, and a multivariate analysis of the
      influence of congestion on tumor recurrence was subsequently completed. No
      significant difference in demographics was found. Group B had more elevated peak
      posttransplant levels of aspartate aminotransferase (296.26 versus 227.53, P =
      0.05), alanine aminotransferase (382.91 versus 276.98, P = 0.04), and highly
      selective C-reactive protein (5.41 versus 3.55, P < 0.001); a higher
      noncongestive section regeneration rate (25.8% versus 13.6%, P = 0.012); and a
      higher recurrence rate (30.4% versus 9.7%, P = 0.01) than group A. Graft
      congestion > 10% [hazard ratio (HR) = 3.10, 95% confidence interval (CI) = 1.15
      8.35, P = 0.03], microvascular invasion (HR = 5.43, 95% CI = 2.04-14.44, P <
      0.01), and an alpha-fetoprotein level > 200 IU/L (HR = 2.98, 95% CI = 1.10-8.03,
      P = 0.03) were significantly related to tumor recurrence. Liver congestion may
      promote the recurrence of HCC after LDLT; therefore, it should be minimized.

PMID- 24668936
TI  - Hypoxia, metabolism, and growth factor signaling in head and neck squamous cell
      carcinoma: correlation between primary and xenograft tumors.
AB  - BACKGROUND: Hypoxia, metabolism, and growth factor signaling are important
      prognostic features in most solid tumors. The purpose of this study was to
      determine whether head and neck squamous cell carcinoma (HNSCC) xenografts show
      similar biological and molecular characteristics as the primary tumor they
      originate from. METHODS: Eighteen HNSCC primary tumor-xenograft pairs were
      immunofluorescently stained for pimonidazole (hypoxia), carbonic anhydrase IX
      (CAIX), glucose transporter-1 (GLUT-1), monocarboxylate transporter-1 (MCT-1),
      monocarboxylate transporter-4 (MCT-4), epidermal growth factor receptor (EGFR),
      and phosphorylated protein kinase B (pAKT). RESULTS: Although no correlation was
      found for the amount of hypoxia, significant correlations between primary tumors
      and xenografts were observed for both the percentage of cells positive for
      expression and the hypoxia-related expression pattern of CAIX, GLUT-1, and MCT-1.
      For EGFR and MCT-4, the intensity of expression was correlated. No correlation
      was observed for pAKT. CONCLUSION: Xenografts did not always resemble the primary
      tumor they originate from, but the xenografts did represent the variability in
      expression levels and patterns observed in the primary tumors.

PMID- 24668937
TI  - In vitro and in vivo co-culture of chondrocytes and bone marrow stem cells in
      photocrosslinked PCL-PEG-PCL hydrogels enhances cartilage formation.
AB  - Chondrocytes (CH) and bone marrow stem cells (BMSCs) are sources that can be used
      in cartilage tissue engineering. Co-culture of CHs and BMSCs is a promising
      strategy for promoting chondrogenic differentiation. In this study, articular CHs
      and BMSCs were encapsulated in PCL-PEG-PCL photocrosslinked hydrogels for 4
      weeks. Various ratios of CH:BMSC co-cultures were investigated to identify the
      optimal ratio for cartilage formation. The results thus obtained revealed that co
      culturing CHs and BMSCs in hydrogels provides an appropriate in vitro
      microenvironment for chondrogenic differentiation and cartilage matrix
      production. Co-culture with a 1:4 CH:BMSC ratio significantly increased the
      synthesis of GAGs and collagen. In vivo cartilage regeneration was evaluated
      using a co-culture system in rabbit models. The co-culture system exhibited a
      hyaline chondrocyte phenotype with excellent regeneration, resembling the
      morphology of native cartilage. This finding suggests that the co-culture of
      these two cell types promotes cartilage regeneration and that the system,
      including the hydrogel scaffold, has potential in cartilage tissue engineering.
      Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668938
TI  - Preparing individual patient data from clinical trials for sharing: the
      GlaxoSmithKline approach.
AB  - In May 2013, GlaxoSmithKline (980 Great West Road, Brentford, Middlesex, TW8 9GS,
      UK) established a new online system to enable scientific researchers to request
      access to anonymised patient level clinical trial data. Providing access to
      individual patient data collected in clinical trials enables conduct of further
      research that may help advance medical science or improve patient care. In turn,
      this helps ensure that the data provided by research participants are used to
      maximum effect in the creation of new knowledge and understanding. However, when
      providing access to individual patient data, maintaining the privacy and
      confidentiality of research participants is critical. This article describes the
      approach we have taken to prepare data for sharing with other researchers in a
      way that minimises risk with respect to the privacy and confidentiality of
      research participants, ensures compliance with current data privacy legal
      requirements and yet retains utility of the anonymised datasets for research
      purposes. We recognise that there are different possible approaches and that
      broad consensus is needed.

PMID- 24668939
TI  - Development of targeted therapies for Parkinson's disease and related
      synucleinopathies.
AB  - Therapeutic efforts in neurodegenerative diseases have been very challenging,
      particularly due to a lack of validated and mechanism-based therapeutic targets
      and biomarkers. The basic idea underlying the novel therapeutic approaches
      reviewed here is that by exploring the molecular basis of neurodegeneration in a
      rare lysosomal disease such as Gaucher's disease (GD), new molecular targets will
      be identified for therapeutic development in common synucleinopathies.
      Accumulation of alpha-synuclein plays a key role in the pathogenesis of
      Parkinson's disease (PD) and other synucleinopathies, suggesting that improved
      clearance of alpha-synuclein may be of therapeutic benefit. To achieve this goal,
      it is important to identify specific mechanisms and targets involved in the
      clearance of alpha-synuclein. Recent discovery of clinical, genetic, and
      pathological linkage between GD and PD offers a unique opportunity to examine
      lysosomal glucocerebrosidase, an enzyme mutated in GD, for development of
      targeted therapies in synucleinopathies. While modulation of glucocerebrosidase
      and glycolipid metabolism offers a viable approach to treating disorders
      associated with synuclein accumulation, the compounds described to date either
      lack the ability to penetrate the CNS or have off-target effects that may
      counteract or limit their capabilities to mediate the desired pharmacological
      action. However, recent emergence of selective inhibitors of glycosphingolipid
      biosynthesis and noninhibitory pharmacological chaperones of glycosphingolipid
      processing enzymes that gain access to the CNS provide a novel approach that may
      overcome some of the limitations of compounds reported to date. These new
      strategies may allow for development of targeted treatments for synucleinopathies
      that affect both children and adults. 

PMID- 24668940
TI  - Hydroxyeicosapentaenoic acids from the Pacific krill show high ligand activities
      for PPARs.
AB  - PPARs regulate the expression of genes for energy metabolism in a ligand
      dependent manner. PPARs can influence fatty acid oxidation, the level of
      circulating triglycerides, glucose uptake and insulin sensitivity. Here, we
      demonstrate that 5-hydroxyeicosapentaenoic acid (HEPE), 8-HEPE, 9-HEPE, 12-HEPE
      and 18-HEPE (hydroxylation products of EPA) obtained from methanol extracts of
      Pacific krill (Euphausia pacifica) can act as PPAR ligands. Two of these
      products, 8-HEPE and 9-HEPE, enhanced the transcription levels of GAL4-PPARs to a
      significantly greater extent than 5-HEPE, 12-HEPE, 18-HEPE, EPA, and EPA ethyl
      ester. 8-HEPE also activated significantly higher transcription of GAL4
      PPARalpha, GAL4-PPARgamma, and GAL4-PPARdelta than EPA at concentrations greater
      than 4, 64, and 64 MUM, respectively. We also demonstrated that 8-HEPE increased
      the expression levels of genes regulated by PPARs in FaO, 3T3-F442A, and C2C12
      cells. Furthermore, 8-HEPE enhanced adipogenesis and glucose uptake. By contrast,
      at the same concentrations, EPA showed weak or little effect, indicating that 8
      HEPE was the more potent inducer of physiological effects.

PMID- 24668942
TI  - Inflammatory activity at school age in very low birth weight bronchopulmonary
      dysplasia survivors.
AB  - OBJECTIVE: Airway inflammation is involved in the pathogenesis of
      bronchopulmonary dysplasia (BPD). The aim of the study was to evaluate the
      inflammatory activity in plasma and exhaled air in very low birth weight (VLBW)
      BPD survivors at school age. METHODS: Twenty-one 6-14-year-old former VLBW (birth
      weight <=1,500 g) children with severe radiographic BPD (radBPD), 19 without
      radBPD (nonBPD group) and 19 non-asthmatic term controls underwent measurement of
      eosinophil cationic protein, IL-6, IL-8, adiponectin, adipsin, leptin, and
      resistin in plasma, leukotriene B4 and 8-isoprostane in exhaled breath
      condensate, and NO in exhaled breath. Background data were obtained from patient
      records, clinical examination and parental questionnaire. Both univariate and
      multivariate models were applied in the statistical analysis. RESULTS: There were
      no significant differences between the groups in any of the inflammatory markers
      measured. Five (25%) radBPD and 2 (11%) nonBPD children reported asthma (P =
      0.058). In logistic regression analysis, exposure to chorioamnionitis was
      associated with low IL-8 (OR 29.0, 95% CI 3.27-258) and postnatal corticosteroid
      therapy with high adiponectin (OR 32.0, 95% CI 1.29-793). High body mass index
      standard deviation score (BMI-SDS) was associated with high plasma adipsin (OR
      2.47, 95% CI 1.07-5.75) and leptin (OR 5.76, 95%CI 1.83-18.2) levels.
      CONCLUSIONS: The inflammatory activity seems to decrease by school age in VLBW
      BPD survivors. Chorioamnionitis and postnatal corticosteroid treatment may
      modulate the inflammatory responsiveness in VLBW subjects even up to school age.
      The respiratory outcome in VLBW infants might be improved by preventing excessive
      weight gain.

PMID- 24668941
TI  - Lysosomal exocytosis and lipid storage disorders.
AB  - Lysosomes are acidic compartments in mammalian cells that are primarily
      responsible for the breakdown of endocytic and autophagic substrates such as
      membranes, proteins, and lipids into their basic building blocks. Lysosomal
      storage diseases (LSDs) are a group of metabolic disorders caused by genetic
      mutations in lysosomal hydrolases required for catabolic degradation, mutations
      in lysosomal membrane proteins important for catabolite export or membrane
      trafficking, or mutations in nonlysosomal proteins indirectly affecting these
      lysosomal functions. A hallmark feature of LSDs is the primary and secondary
      excessive accumulation of undigested lipids in the lysosome, which causes
      lysosomal dysfunction and cell death, and subsequently pathological symptoms in
      various tissues and organs. There are more than 60 types of LSDs, but an
      effective therapeutic strategy is still lacking for most of them. Several recent
      in vitro and in vivo studies suggest that induction of lysosomal exocytosis could
      effectively reduce the accumulation of the storage materials. Meanwhile, the
      molecular machinery and regulatory mechanisms for lysosomal exocytosis are
      beginning to be revealed. In this paper, we first discuss these recent
      developments with the focus on the functional interactions between lipid storage
      and lysosomal exocytosis. We then discuss whether lysosomal exocytosis can be
      manipulated to correct lysosomal and cellular dysfunction caused by excessive
      lipid storage, providing a potentially general therapeutic approach for LSDs.

PMID- 24668944
TI  - Brief report. Adult patient presenting an interstitial (9) (q21.32q31.1) direct
      duplication resulting from the malsegregation of a paternal balanced insertional
      translocation.
AB  - BACKGROUND: The partial trisomy 9q syndrome is a well-defined chromosomal
      disorder with over 40 reported cases in the literature. However, 9q duplications
      derived from an insertional translocation have rarely been reported. METHODS:
      Cytogenetic and molecular analyses using G-banding, fluorescence in situ
      hybridization, and single nucleotide polymorphism array were performed in a 25
      year-old male patient with intellectual disability, behavioral abnormalities,
      speech delay, postnatal growth retardation, distinctive facial features, and
      pyloric stenosis. RESULTS: G-banding analysis showed an extra chromosome segment
      of unknown origin inserted into band 4q25. A 16,747,601 bp duplication of
      9q21.32q31.1 inserted into band 4q25 and a balanced (4;9) insertional
      translocation were identified by single nucleotide polymorphism array and
      fluorescence in situ hybridization analysis respectively in the patient and his
      healthy father. A literature review was performed to refine genotype-phenotype
      correlation of the partial trisomy 9q syndrome. CONCLUSION: This is the first
      report on the molecular characterization of a partial trisomy 9q syndrome derived
      from an insertional translocation between nonhomologous chromosomes. Our findings
      provide important information for genetic counseling and prenatal diagnosis of
      future pregnancies in this family.

PMID- 24668943
TI  - Transplantation of cancerous cell sheets effectively generates tumour-bearing
      model mice.
AB  - Tumour-bearing mice were created by transplanting cancerous cell sheets onto the
      subcutaneous tissue of the dorsal region, using luciferase gene-transfected
      mammary gland adenocarcinoma cells, 4T1-luc2, to investigate the tumourigenicity
      of the cell sheet relative to a conventional injection of cell suspension.
      Contiguous breast cancerous cell sheets were harvested from temperature
      responsive culture dishes by reducing the temperature from 37  degrees C to 20 
      degrees C; the sheets were then transplanted onto the dorsal side of the mouse
      subcutaneous tissue, using a chitin-based supporting membrane. Cell suspensions
      obtained by trypsin digestion were subcutaneously injected into the dorsal region
      of mice. The tumour growth of the transplanted cancer cells was evaluated by the
      tumour volume and by the bioluminescence from luciferase-gene transfected cancer
      cells, using an in vivo imaging system. The cell sheet method improved the 4 T1
      luc2 engraftment efficiency in living mouse tissues at the initial stage by 13
      fold compared with that from injecting cell suspensions. On day 14 after the
      transplantation, the tumour formation at the transplanted area of cell sheet
      transplanted mice also accelerated, and the mean tumour volume became 1116 mm3 ,
      which was 10 times larger than that in cell suspension-transplanted mice. The
      cell sheets engrafted on the recipient tissues efficiently due to the preserved
      extracellular matrix on their basal sides, such that cancer cells were supplied
      with sufficient oxygen and nutrients from the host tissues to develop tumour
      tissues. Therefore, cancerous cell sheet-based transplantation is a promising
      method for efficiently creating cancer-bearing mice. Copyright (c) 2013 John
      Wiley & Sons, Ltd.

PMID- 24668945
TI  - Endothelial colony-forming cells for preparing prevascular three-dimensional cell
      dense tissues using cell-sheet engineering.
AB  - Vascular-derived endothelial cell (EC) network prefabrication in three
      dimensional (3D) tissue constructs before transplantation is useful for inducing
      functional anastomosis with the host vasculature. However, the clinical
      application of ECs is limited by cell isolation from the existing vasculature,
      because of the requirement for invasive biopsies and difficulty in obtaining a
      sufficient number of cells. Endothelial colony-forming cells (ECFCs), which are a
      subtype of endothelial progenitor cells in the blood, have a strong proliferative
      and vasculogenic potential. This study attempted to fabricate prevascular 3D cell
      dense tissue constructs using cord blood-derived ECFCs and evaluate the in vivo
      angiogenic potential of these constructs. Human umbilical vascular endothelial
      cells (HUVECs) were also used in comparison with ECFCs, which were sandwiched
      between two human dermal-derived fibroblast (FB) sheets using a fibrin-coated
      cell-sheet manipulator. The inserted ECFCs in double-layered FB sheets were
      cultured for 3 days, resulting in the formation of network structures similar to
      those of HUVECs. Additionally, when ECFCs were sandwiched with three FB sheets, a
      lumen structure was found in the triple-layered cell-sheet constructs at 3 days
      after co-culture. These constructs containing ECFCs were transplanted into the
      subcutaneous tissue of immune-deficient rats. One week after transplantation,
      ECFC-lined functional microvessels containing rat erythrocytes were observed in
      the same manner as transplanted HUVEC-positive grafts. These results suggest that
      ECFCs might become an alternative cell source for fabricating a prevascular
      structure in 3D cell-dense tissue constructs for clinical application. Copyright
      (c) 2013 John Wiley & Sons, Ltd.

PMID- 24668946
TI  - Conventional and molecular cytogenetic characterization of Burkitt lymphoma with
      bone marrow involvement in Brazilian children and adolescents.
AB  - BACKGROUND: Burkitt lymphoma/leukemia (BL/L) is cytogenetically characterized by
      the t(8;14)(q24;q32) or its variants, t(2;8)(p11;q21), and t(8;22)(q24;q11.2),
      which juxtapose the MYC oncogene to one of the three immunoglobulin loci. The
      overall cure rate of BL/L in children is 70-90%, but patients diagnosed with
      advanced-stage disease have a less favorable prognosis. It is possible that
      secondary chromosomal abnormalities contribute to this unfavorable prognosis via
      chemotherapy resistance, but the results of genetic studies have been
      inconsistent. This study aimed to identify and characterize secondary chromosomal
      abnormalities associated with the t(8;14) and its variants in children with
      French-American-British-L3 leukemia or Burkitt lymphoma with bone marrow
      involvement at the time of diagnosis. PROCEDURE: Chromosome analysis was based on
      G-banding. Fluorescence in situ hybridization technique was applied using
      IGH/MYC/CEP8 dual-fusion and MYC break-apart probes. Multicolor chromosome
      banding was performed according to standard protocol. RESULTS: We describe a
      group of BL/L with extreme adverse clinical outcome, in which secondary
      chromosomal abnormalities, particularly those involving the long arms of
      chromosomes 1 and 13, were found in 71% of cases. The IGH/MYC fusion showed
      molecular heterogeneity in 14% of cases and two cases exhibited three IGH/MYC
      fusion signals. CONCLUSIONS: Secondary chromosomal abnormalities were found in a
      high proportion of patients. We observed an extent of IGH/MYC heterogeneity not
      previously reported in Burkitt lymphoma, including the novel finding of three
      fusion signals in two cases.

PMID- 24668947
TI  - Early therapy-related myeloid sarcoma and deletion of 9q22.32 to q31.1.
AB  - Survival following childhood neuroblastoma is improving with low rates of
      secondary myeloid neoplasms. We describe a 13-month-old male with intermediate
      risk neuroblastoma who developed an isolated scalp therapy-related myeloid
      sarcoma (t-MS). Developmental delays and two distinct malignancies prompted
      constitutional evaluation. Chromosomal microarray identified a 7.3 Mb deletion of
      9q22.32 to 9q31.1. He remains in remission 11 months following hematopoietic cell
      transplant. Unusual presentations of rare diseases necessitate a
      multidisciplinary approach and adaptation of standardized protocols to
      accommodate increased risks imposed by genetic variants.

PMID- 24668948
TI  - An automated, high-throughput method for targeted quantification of intact
      insulin and its therapeutic analogs in human serum or plasma coupling mass
      spectrometric immunoassay with high resolution and accurate mass detection (MSIA
      HR/AM).
AB  - The detection and quantification of insulin and its therapeutic analogs is
      important for medical, sports doping, and forensic applications. Synthetic
      variants contain slight sequence variations to affect bioavailability. To reduce
      sample handling bias, a universal extraction method is required for simultaneous
      extraction of endogenous and variant insulins with subsequent targeted
      quantification by LC-MS. A mass spectrometric immunoassay (MSIA), a multiplexed
      assay for intact insulin and its analogues that couples immunoenrichment with
      high resolution and accurate mass (HR/AM) spectrometric detection across the
      clinical range is presented in this report. The assay is sensitive, selective,
      semi-automated and can potentially be applied to detect new insulin isoforms
      allowing their further incorporation into second or third generation assays. 

PMID- 24668950
TI  - Mobile bag starch prececal disappearance and postprandial glycemic response of
      four forms of barley in horses.
AB  - To determine prececal starch digestibili-ty and estimate glucose uptake from the
      digestion of 4 forms of barley in the small intestine, 4 mature cecally
      fistulated geldings (449 +/- 41 kg BW) fed a 62:38 (wt/wt) meadow hay:concentrate
      diet at 1.7 kg DM/100 kg BW were included in a 4 * 4 Latin square design
      experiment. During each period, horses received 80% DM of their concentrate as 1
      of the 4 forms of a same batch of barley, whole grain, 2.5 mm ground, steam
      flaked, and pelleted. Hay was offered in 2 equal meals and concentrate in 2
      unequal meals. The starch supply in the morning meal amounted 2.7 g starch/kg BW.
      At each period, mobile bag DM and starch disappearance was determined. Except for
      ground barley, each form of barley was 4 mm ground before being introduced in the
      bag. Nylon bags containing each substrate were intubated in the horse receiving
      the pelleted barley. Bags were collected in the cecum for 10 h postintubation. At
      each period, postprandial glycemia was measured on blood samples collected on the
      4 horses via an indwelling jugular catheter just before the concentrate morning
      meal and for 8 h. No hay in the morning meal was given the day of the
      measurements. Whole blood glucose was analyzed with a portable blood glucose
      meter. Mobile bag prececal DM disappearance and starch disappearance depended (P
      < 0.01) on barley form. Prececal starch disappearance of whole barley was the
      lowest but no difference (P > 0.05) was detected among the 3 processed grains. No
      significant effect of barley form was found whatever the glycemic parameters. No
      significant correlation was reported between glycemic parameters and the amount
      of prececal mobile bag disappeared starch calculated as the starch intake in the
      morning meal by the mobile bag starch disappearance. To conclude, the whole form
      of barley exhibited the lowest prececal mobile bag starch disappearance whereas,
      in relationship with large individual variations, no significant variation has
      been shown in glycemic parameters. Further investigations should be performed to
      improve methods for estimating prececal starch digestion of processed cereals in
      the different digestive segments of horses. 

PMID- 24668949
TI  - Dexrazoxane exposure and risk of secondary acute myeloid leukemia in pediatric
      oncology patients.
AB  - BACKGROUND: Dexrazoxane may reduce anthracycline-associated cardiotoxicity in
      pediatric cancer patients. However, concerns of secondary acute myeloid leukemia
      (AML) have led to restrictions on pediatric dexrazoxane use in Europe. Published
      data about dexrazoxane-associated secondary AML are limited and conflicting. We
      sought to estimate the secondary AML risk in children receiving dexrazoxane after
      anthracycline exposure. PROCEDURE: A retrospective cohort of children with newly
      identified malignancies (excluding AML) receiving anthracyclines between January
      1, 1999 and March 31, 2011 was established using the Pediatric Health Information
      System (PHIS). Patients were followed for all subsequent admissions to identify
      dexrazoxane exposures and secondary AML, defined by AML ICD-9 codes and AML
      induction chemotherapy. Logistic regression was used to model the association of
      dexrazoxane and secondary AML risk. A propensity score was used to adjust for
      measurable confounding. RESULTS: Of 15,532 patients in the cohort exposed to
      anthracyclines, 1,406 received dexrazoxane. The secondary AML rate was 0.21% (3
      of 1,046) in dexrazoxane-exposed and 0.55% (77 of 14,126) in unexposed patients.
      In a propensity score-adjusted multivariate analysis, dexrazoxane exposure was
      not associated with an increased risk of secondary AML, OR = 0.38, 95% CI 0.11
      1.26. CONCLUSIONS: Dexrazoxane was not associated with an increased risk of
      secondary AML in a large cohort of pediatric cancer patients receiving
      anthracyclines in US hospitals. While these data support dexrazoxane's safety in
      the general pediatric oncology population, additional studies are needed to
      confirm these findings and to quantify dexrazoxane's long-term cardioprotective
      effects.

PMID- 24668951
TI  - A new application of pelvis area data as culling tool to aid in the management of
      dystocia in heifers.
AB  - Although fetomaternal disproportion is the major cause of dystocia in heifers,
      pelvis area (PA) is not recommended as a culling tool due to its relatively low
      importance and genetic correlation with calf birth weight (BWT), the most
      important factor associated with dystocia. The objective of this observational
      study of 484 limited bred yearling beef heifers was to compare the effects of
      different methods of adjustment of PA data for culling to select against
      dystocia. Multivariable analyses were used to determine predictors of PA, calf
      BWT, and dystocia. Hypothetical culling rates of 10 and 20% were then applied
      after ranking heifers by each of the following: unadjusted PA, PA adjusted to 365
      d of age by subtracting 0.27 cm(2) per day of age difference between each
      heifer's age and 365 d (APA), PA:prebreeding BW ratio (PA:BW), PA adjusted to the
      median BW of the group using the regression coefficient of PA on BW within age
      group (BWPA), and PA similarly adjusted to the median lean BW (LBWPA). Dam
      parity, sire, prebreeding age, prebreeding BW, and prebreeding BCS were
      associated with PA whereas dam parity, sire, own BWT, PA, AI bull, and calf
      gender were associated with calf BWT (P < 0.05). Dam parity, calf BWT, and either
      BWPA or LBWPA were the only independent predictors of dystocia (P < 0.05).
      Adjusting PA to BW or lean BW (LBW) improved the sensitivity and specificity to
      predict dystocia. After hypothetical culling by PA, retained heifers were heavier
      and had a higher calving rate and calves tended to be heavier at birth compared
      to culled heifers, but dystocia rates were not different. Culling by APA resulted
      in similar effects, except that dystocia rate tended to be lower in retained
      heifers. Culling by PA:BW resulted in lower dystocia rate in retained than in
      culled heifers, but retained heifers had lower prebreeding BW than culls. Culling
      by BWPA and LBWPA resulted in lower proportions with dystocia and a tendency
      towards higher calving rates in the retained heifers, without affecting the
      prebreeding BW or calf BWT. It is concluded that pelvimetry is a useful culling
      tool to aid in the management of dystocia in yearling heifers and that adjustment
      of PA to median BW or LBW within age group improves its accuracy and avoids the
      undesirable side effects. 

PMID- 24668952
TI  - Impact of sensory feed additives on feed intake, feed preferences, and growth of
      female piglets during the early postweaning period.
AB  - Our study aimed at investigating the effect of feed supplementation, from
      weaning, with 3 sensory feed additives (FA1, FA2, and FA3) on feed preferences,
      feed intake, and growth of piglets. The FA1 contained extract of Stevia
      rebaudiana (10 to 20%), extract of high-saponin plants (5 to 10%), and excipients
      (70 to 85%), the FA2 was mainly composed of a natural extract of Citrus sinensis
      (60 to 80%), and the FA3 was made of a blend of extracts of hot-flavored spices
      (5 to 15%) and excipients (85 to 95%). At weaning (d 1), a total of 32 female
      piglets housed in individual pens were allocated to 4 treatments (FA1, FA2, FA3,
      and control [CON]) of equivalent mean weight. The pigs were fed a standard
      pelleted prestarter diet from weaning (d 1) to d 15 and a starter diet from d 16
      to 28. The diets were supplemented with the feed additives (FA) corresponding to
      their treatment, while the CON treatment was the standard diets with no additive.
      Feed refusals were weighed daily and piglets were weighed weekly on d 1, 7, 14,
      21, and 28. On the day of feed transition (d 16) as well as 7 (d 23) and 10 d (d
      26) later, the animals were consecutively subjected to 1- and 22-h double-choice
      feeding tests to investigate their preferences during a short period and a longer
      period of time for the CON starter diet and the starter diet added with the FA
      corresponding to their treatment. No overall effect of the feed additives was
      observed on ADFI, ADG, G:F, and final BW. No overall preference was highlighted
      for the FA1 treatment, except for a preference for the FA1 starter diet during
      the 1-h test on d 23 (78% of total feed intake; P < 0.01). For the FA2 treatment,
      the pigs consumed the FA2 starter diet more than the CON starter diet during the
      22-h tests on d 16 (67% of total feed intake; P < 0.05) and 26 (62% of total feed
      intake; P < 0.01). For the FA3 treatment, on d 26, the FA3 starter diet was and
      tended to be consumed more than the CON starter diet during 1- (69% of total
      intake; P < 0.05) and 22-h (60% of total intake; P < 0.10) tests, respectively.
      In conclusion, feed supplementation with the FA1, FA2, and FA3 from weaning did
      not induce beneficial effects on feed intake and growth performance during the
      early postweaning period. The FA2 increased palatability and acceptance of the
      unfamiliar starter diet the day of feed transition, while the FA1 and FA3
      increased palatability of the starter diet only after a few days of exposure,
      most likely through long-term familiarization processes. 

PMID- 24668953
TI  - Effect of beef heifer development system on average daily gain, reproduction, and
      adaptation to corn residue during first pregnancy.
AB  - Postweaning heifer development systems were evaluated at 2 locations in a 4-yr
      study for their effect on performance and subsequent adaptation to grazing corn
      residue as a pregnant heifer. In Exp. 1, heifers were blocked by BW and randomly
      assigned to graze winter range (WR) or graze winter range and corn residue (CR).
      In Exp. 2, heifers were assigned to graze winter range and corn residue (CR) or
      graze winter range and placed in a drylot (DL). Artificial insemination and
      natural mating were used at breeding on the basis of location. In Exp. 1, heifers
      developed on corn residue tended (P = 0.11) to have reduced ADG compared with WR
      heifers. Subsequently, BW at the end of the 82-d corn residue grazing period
      tended (P = 0.09) to be lower for CR compared with WR heifers. However, the
      proportion of heifers attaining puberty before the breeding season and pregnancy
      rates were similar (P >= 0.29) for CR and WR heifers. Developing heifers on
      winter range tended (P = 0.09) to reduce heifer development costs $36/pregnant
      heifer compared with CR heifers. In Exp. 2, DL heifers had greater (P < 0.01)
      overall ADG during development compared with CR heifers, resulting in greater (P
      < 0.01) prebreeding BW for DL heifers compared with CR heifers (355 vs. 322 +/- 9
      kg). At pregnancy diagnosis BW remained greater (P = 0.02) for DL compared with
      CR heifers (423 vs. 406 +/- 7 kg). Corn-residue-developed heifers had increased
      (P = 0.03) AI conception rates compared with DL heifers (78% vs. 67% +/- 6%).
      However, there was no difference (P >= 0.21) in percent pubertal before the
      breeding season or final pregnancy rates for CR and DL heifers. Developing
      heifers on corn residue reduced (P = 0.02) heifer development costs $38/pregnant
      heifer compared with DL-developed heifers. A subset of pregnant heifers from both
      experiments grazed corn residue fields in late gestation. As pregnant heifers
      grazing corn residue, WR heifers (Exp. 1) tended to have reduced ADG compared
      with CR heifers (0.34 vs. 0.43 +/- 0.08 kg/d, P = 0.07). Furthermore, in Exp. 2
      CR heifers had greater (0.41 vs. 0.30 +/- 0.22 kg/d) ADG grazing corn residue as
      pregnant heifers compared with DL-developed heifers. Calving date, dystocia
      score, and calf birth BW were similar (P >= 0.15) between development systems in
      both experiments. There appears to be a potential learned grazing behavior for
      heifers developed on corn residue allowing them to better adapt to grazing corn
      residue as pregnant heifers compared with WR and DL heifers. 

PMID- 24668955
TI  - Group space allowance has little effect on sow health, productivity, or welfare
      in a free-access stall system.
AB  - Free-access stalls allow sows to choose the protection of a stall or use of a
      shared group space. This study investigated the effect of group space width, 0.91
      (SS), 2.13 (IS), and 3.05 (LS) m, on the health, production, behavior, and
      welfare of gestating sows. Nine replications of 21 (N = 189) gestating sows were
      used. At gestational d 35.4 +/- 2.3, the pregnant sows were distributed into 3
      pens of 7 sows, where they remained until 104.6 +/- 3.5 d. Each treatment pen had
      7 free-access stalls and a group space that together provided 1.93 (SS), 2.68
      (IS), or 3.24 (LS) m(2)/sow. Baseline measurements were obtained before mixing.
      Back fat depth, BW, BCS, and lameness were measured monthly, and skin lesions
      were scored weekly. Blood was collected monthly for hematological, immunological,
      and cortisol analyses. Sow behavior was video recorded continuously during the
      initial 4 d of treatment and 24 h every other week thereafter. Behavior was
      analyzed for location, posture, pen investigation, social contact, and
      aggression. Skin response to the mitogen concanavalin A (Con A) was tested at
      mean gestational d 106. Litter characteristics including size and weight were
      collected at birth and weaning. The data were analyzed using a mixed model.
      Multiple comparisons were adjusted with the Tukey-Kramer and Bejamini-Hochberg
      methods. Group space allowance had no effect on any measure of sow health,
      physiology, or production (P >= 0.10). Sows in the SS, IS, and LS pens spent
      77.88% +/- 3.88%, 66.02% +/- 3.87%, and 63.64% +/- 3.91%, respectively, of their
      time in the free-access stalls (P = 0.12). However, SS sows used the group space
      less than IS and LS sows (P = 0.01). Overall, pen investigatory behavior was not
      affected by group space allowance (P = 0.91). Sows in the LS pens spent more time
      in a social group than SS sows (P = 0.02), whereas sows in IS pens were
      intermediate to, but not different from, the other treatments (P >= 0.10). The
      size of the social groups was also affected by the group space allowance (P =
      0.03), with SS sows forming smaller groups than LS sows; again, IS sows were
      intermediate to, but not different from, the other treatments. Although the group
      space allowance had no measurable impact on the health, physiology, or
      productivity of the sows, the lower group space use and social contact of the SS
      sows reduced the behavioral diversity benefits of group housing and may indicate
      an avoidance of social stressors or a lack of physical comfort in the smallest
      pens. 

PMID- 24668954
TI  - Dose-response of supplementing marine algae (Schizochytrium spp.) on production
      performance, fatty acid profiles, and wool parameters of growing lambs.
AB  - Microalgae are the original source of docosahexaenoic acid (DHA; 22:6n-3) in the
      marine food chain, and its inclusion in animal feeds has been considered as a
      means of increasing the DHA level in foods of animal origin. As such, this study
      aimed to investigate the effects of supplementing an algal meal, high in DHA
      derived from Schizochytrium spp. (DHA-G), in the diet of Canadian Arcott lambs,
      on growth, carcass characteristics, wool production, and fatty acid (FA) profiles
      of subcutaneous adipose tissues (SAT), perirenal adipose tissues (PAT), and skirt
      muscle (SM). Forty-four lambs were randomly assigned to dietary treatments. Diets
      consisted of a pelleted, barley-based finishing diet with DHA-G supplemented at
      0, 1, 2, or 3% DM as a replacement for flax oil and barley grain. Feed deliveries
      and orts were recorded daily. Lambs were weighed weekly and slaughtered once they
      reached >= 45 kg live weight. Carcass characteristics, ruminal pH, and liver
      weights were determined at slaughter. Wool yield was determined on mid-side
      patches of 100 cm(2) shorn at d 0 and on the day before slaughter (d 105 or 140).
      Dye bands were used to determine wool growth, fiber diameter, and staple length.
      Adipose tissues and SM samples were taken at slaughter and analyzed for FA
      profiles. Data were analyzed using mixed procedure in SAS with orthogonal
      contrasts testing for linear, quadratic, or cubic responses to increasing levels
      of DHA-G. Daily DMI, ADG, and G:F were similar as were wool quality and yield (P
      > 0.05). Carcass characteristics were generally unaffected (P > 0.05), except for
      body wall thickness (mm), which showed a quadratic response (P = 0.01) with
      increasing DHA-G. The concentration of eicosapentaenoic acid (EPA; 20:5n-6;
      mg/100 g fresh tissue) linearly increased (P < 0.001) with DHA-G in both adipose
      tissues and responded quadratically in SM (P = 0.05). Similarly, DHA (mg/100 g
      fresh tissue) increased linearly (P < 0.01) with DHA-G in all tissue types (P <
      0.001). Supplementing DHA-G decreased (P < 0.001) the n-6:n-3 ratio in all
      tissues. No effects (P >= 0.05) on PUFA or SFA were observed across the 3
      tissues, with no response (P >= 0.10) in the SFA:PUFA ratio in either SM or SAT;
      however, the SFA:PUFA ratio linearly decreased in PAT (P = 0.01) as DHA-G
      increased. These results indicate that DHA-G can be successfully included in the
      diets of growing lambs, up to 3% DM, with the potential to improve carcass
      characteristics and the FA profile of adipose tissue and muscle.

PMID- 24668956
TI  - Effect of growth hormone on the differentiation of bovine preadipocytes into
      adipocytes and the role of the signal transducer and activator of transcription
      5b.
AB  - We evaluated the effect of GH on the differentiation of primary bovine
      preadipocytes into adipocytes. Bovine preadipocytes, derived from adipose tissue
      explants, were induced to differentiate into adipocytes in the presence or
      absence of recombinant bovine GH. The differentiation status of adipocytes was
      assessed by Oil Red O staining and by measuring the activity of glycerol-3
      phosphate dehydrogenase (G3PDH) and the rate of acetate incorporation. Fewer
      preadipocytes became adipocytes in the presence of GH than in the absence of GH;
      adipocytes formed in the presence of GH had lower G3PDH activity and lower rate
      of acetate incorporation than those formed without GH treatment (P < 0.05). These
      data suggest an inhibitory effect of GH on the differentiation of bovine
      preadipocytes into adipocytes. Growth hormone decreased the expression of
      C/EBPalpha and PPARgamma mRNA in bovine adipocytes (P < 0.05). Because C/EBPalpha
      and PPARgamma are the master regulators of adipocyte differentiation, this data
      suggests that GH might inhibit the differentiation of bovine preadipocytes into
      adipocytes by inhibiting the expression of C/EBPalpha and/or PPARgamma. Because
      the signal transducer and activator of transcription 5 (STAT5) is a major
      component of signaling from the GH receptor, we next determined the potential
      role of STAT5 in GH inhibition of bovine adipocyte differentiation.
      Overexpression of a constitutively active form of STAT5b (STAT5bCA) in bovine
      preadipocytes through adenoviral transduction mimicked the effects of GH on the
      formation of lipid-containing adipocytes, G3PDH activity, and acetate
      incorporation rate. Overexpression of STAT5bCA was associated with decreased
      expression of C/EBPalpha mRNA (P < 0.05) but not that of PPARgamma mRNA in bovine
      adipocytes. These results support a role of STAT5b in mediating GH inhibition of
      C/EBPalpha expression but not that of PPARgamma expression in bovine
      preadipocytes. Overall, the present study suggests that GH may inhibit adipose
      growth in cattle in part by inhibiting adipogenesis and that GH inhibits the
      differentiation of bovine preadipocytes to adipocytes through STAT5b-dependent
      inhibition of C/EBPalpha expression and STAT5b-independent inhibition of
      PPARgamma expression. 

PMID- 24668957
TI  - Neonatal surgical castration of male pigs reduces thymic growth but has moderate
      consequences on thymocytes.
AB  - Thymus integrates numerous signals from the neuroendocrine-immune system,
      including sex steroids, glucocorticoids, and catecholamines. Neonatal surgical
      castration, commonly practiced in pig husbandry, modifies thymic hormonal
      environment, for example, sex steroids and probably glucocorticoids and
      catecholamines, which are important modulators of thymic function. This study
      aimed at investigating, in pubescent male pigs, the consequences of neonatal
      suppression of testicular hormones on thymic T cell differentiation and hormonal
      control of thymocyte proliferation. A total of 34 male pigs were allocated to 2
      experimental groups: control (CT) intact males and males surgically castrated
      (SC) at 5 or 6 d of age. At slaughter, thymus was weighed and thymic samples were
      collected to determine fat content and distribution of thymocyte subsets by
      identification of CD1, CD4, CD8, and gammadelta T cell receptor (TCR) cell
      surface markers and to measure thymocyte proliferation in presence of cortisol,
      norepinephrine, and sex steroids. Results showed that absolute and relative
      thymus weights were greater (P < 0.01 and P < 0.01, respectively) whereas thymic
      fat content was less (P < 0.01) in CT than in SC pigs. Surgical castration did
      not change the frequency of CD1+ immature thymocytes. The proportion of
      gammadelta T cells tended to be greater in CT than in SC pigs (P < 0.1) but the
      proportions of CD4+, CD8+, and CD4+CD8+ thymocytes were similar in both groups (P
      > 0.1) indicating that the Talphabeta lineage was not influenced by early
      castration. Proliferation of thymocytes in response to concanavalin A (ConA) was
      greater in SC than in CT pigs (P < 0.05). Cortisol and norepinephrine decreased
      the ConA-induced proliferation in CT and SC pigs (P < 0.05). In addition,
      proliferation of thymocytes was less inhibited by norepinephrine in SC than in CT
      males (P < 0.05). The greatest concentration of testosterone (25 ng/mL) increased
      (SC males, P < 0.05) or tended to increase (CT males, P < 0.1) the proliferative
      responsiveness to ConA but the lowest dose (2.5 ng/mL) and the greatest dose of
      testosterone combined with estradiol had no significant effect (P > 0.1).
      Overall, our data show little effect of neonatal castration on thymocyte
      differentiation as well as of sex hormones on thymocyte proliferation. However,
      thymic cells seem to be more sensitive to the inhibitory influence of
      norepinephrine in CT than in CS pigs. The significance of such difference for
      animal health remains to be explored. 

PMID- 24668958
TI  - The effects of immunological castration and corn dried distillers grains with
      solubles withdrawal on growth performance, carcass characteristics, fatty acid
      analysis, and iodine value of pork fat depots.
AB  - A total of 1,360 pigs were used in a 125-d study to determine the effects of corn
      dried distillers grains with solubles (DDGS) withdrawal after immunological
      castration (Improvest, Zoetis, Kalamazoo, MI) on growth performance and carcass
      fat quality of pigs. Pens of male pigs (initially 24 kg) were randomly allotted
      by BW and castration method (physically castrated [PC] or immunologically
      castrated [IC] barrows) to 1 of 3 diets with 8 replications per treatment and 27
      to 29 pigs per pen. Treatments were arranged in a 2 * 3 factorial with main
      effects of castration method and diet (0% DDGS throughout, 30% DDGS throughout,
      or 30% DDGS through d 75 then no DDGS to d 125). Intact males were injected with
      Improvest on d 39 and 74 (IC). No castration method * diet interactions (P >
      0.12) were observed for growth performance. Before the second Improvest injection
      (d 0 to 74), PC barrows had increased (P < 0.05) ADFI but were less efficient (P
      < 0.05) than intact males. After the second Improvest injection until the first
      marketing event (d 74 to 107), IC barrows had improved (P < 0.05) ADG and G:F
      compared with PC barrows. From d 0 to 107, IC barrows had improved (P < 0.05)
      ADG, G:F, and lower ADFI than PC barrows. The inclusion of 30% DDGS decreased (P
      < 0.05) G:F compared with pigs fed the control diet. For the period after the
      second Improvest injection (d 74 to 125), IC barrows had increased (P < 0.05)
      ADG, ADFI, and G:F compared with PC barrows. Overall (d 0 to 125), IC barrows had
      improved (P < 0.05) ADG and G:F and lower ADFI than PC barrows. The inclusion of
      30% DDGS decreased (P < 0.05) G:F. Carcass yield was lower (P < 0.05) for IC than
      PC barrows. Pigs fed 30% DDGS throughout had decreased (P < 0.05) carcass yield;
      however, withdrawing DDGS from the diet on d 74 was effective at fully recovering
      the yield loss. Carcass fat iodine values (IV) were consistently higher (P <
      0.05), regardless of fat depot or harvest time when 30% DDGS were included in the
      diet. Multiple 2-way interactions (P < 0.05) were detected between castration
      method, DDGS, depot, and time. Interactions were a result of fatty acid profiles
      changing more rapidly in backfat and belly fat than in jowl fat from d 107 to 125
      and more dramatically in IC than PC barrows in the same period. This improvement
      from d 107 to 125 could be caused by the dilution of unsaturated fatty acids,
      specifically C18:2 and C18:3, due to rapid deposition of fat from de novo
      synthesis in IC barrows. 

PMID- 24668959
TI  - Feeding glycerol-enriched yeast culture improves performance, energy status, and
      heat shock protein gene expression of lactating Holstein cows under heat stress.
AB  - This study was conducted to evaluate the effects of supplemental common yeast
      culture (CY) and glycerol-enriched yeast culture (GY) on performance, plasma
      metabolites, antioxidant status, and heat shock protein 70 (HSP70) mRNA
      expression in lactating Holstein cows under heat stress. During summer months, 30
      healthy multiparous lactating cows (parity 3.25 +/- 0.48; 60 +/- 13 d in milk
      [DIM]; 648 +/- 57 kg BW; an average milk yield of 33.8 +/- 1.6 kg/d) were blocked
      by parity, previous milk yield, and DIM and randomly allocated to 3 dietary
      treatments: no supplemental yeast culture (Control), 1 L/d of CY (33.1 g yeast)
      per cow, and 2 L/d of GY (153.2 g glycerol and 31.6 g yeast) per cow. During the
      60-d experiment, values of air temperature and relative humidity inside the barn
      were recorded hourly every 3 d to calculate temperature-humidity index (THI).
      Weekly rectal temperatures (RT) and respiration rates and daily DMI and milk
      yield were recorded for all cows. Milk and blood samples were taken twice
      monthly, and BW and BCS were obtained on d 0 and 60. In this experiment, THI
      values indicated cows experienced a moderate heat stress. Cows supplemented with
      CY and GY had greater yields of milk, energy-corrected milk and milk fat, and
      milk fat percent but lower HSP70 mRNA expression in peripheral blood lymphocytes
      than Control cows (P < 0.05). Supplementing CY and GY tended (P < 0.15) to
      decrease RT at 1400 h, increase milk protein yield and erythrocyte glutathione,
      and reduce plasma urea nitrogen compared with Control. Lower plasma NEFA
      concentration and HSP70 mRNA expression in peripheral blood lymphocytes (P <
      0.05) and tendencies towards greater plasma glucose concentration (P = 0.11) but
      less BW loss (P = 0.14) were observed in GY relative to CY cows. In conclusion,
      either CY or GY supplementation partially mitigated the negative effects of heat
      stress on performance and HSP70 mRNA expression of lactating cows, and GY
      supplementation provided additional improvements in energy status and HSP70 gene
      expression of lactating cows. 

PMID- 24668960
TI  - Effect of graded inclusion of dietary soybean meal on nutrient digestibility,
      health, and metabolic indices of adult dogs.
AB  - Two studies were conducted using adult dogs to evaluate the effect of increasing
      the inclusion of soybean meal (SBM) in an adult dog food on body composition,
      hematological and biochemical blood analyses, and total tract nutrient
      digestibility. Nutritionally complete and balanced diets were formulated with
      commercial-grade SBM (48% CP) to replace 0, 10, 20, or 30% of the protein
      provided by dried chicken protein resulting in final SBM inclusion of 0, 6.0,
      11.5, and 17.0% (as-fed basis), respectively. In study 1, diets were fed during a
      24-wk feeding trial using 36 female (spayed), adult hounds to evaluate food
      intake, BW, body composition, and blood measurements. There were no diet-related
      differences in food intake or BW. Body composition responded in a quadratic
      manner to increased dietary SBM inclusion with the percentage (%) of lean mass
      responding positively (P < 0.05) and absolute amounts of fat mass and percent
      body fat responding negatively (P < 0.05). All diagnostic blood components
      remained within normal physiological ranges for healthy, adult dogs. Serum
      concentrations of C-reactive protein and IGF-1 were similar among diets. In study
      2, diets were evaluated in a digestibility study using 12 adult dogs in a 4 * 4
      Latin square design. Increased SBM inclusion was associated with linear increases
      in the digestibility of CP (P < 0.05) and fat (P < 0.05) and CP retention (P <
      0.05). Linear reductions in fecal DM content (P < 0.01) and increased fecal
      output (P < 0.05) were noted with increased SBM inclusion. All diets were similar
      in DE and ME content, but a quadratic trend was noted with increased SBM
      inclusion when DE (P = 0.083) and ME (P = 0.062) were expressed per unit of
      metabolic body size. Overall, it can be inferred from these results that the
      partial replacement of dried chicken protein with SBM in a nutritionally complete
      and balanced diet does not compromise the nutritional status and long-term health
      of adult dogs. 

PMID- 24668961
TI  - Extent of mismatch between the period of circadian clocks and light/dark cycles
      determines time-to-emergence in fruit flies.
AB  - Circadian clocks time developmental stages of fruit flies Drosophila
      melanogaster, while light/dark (LD) cycles delimit emergence of adults, conceding
      only during the "allowed gate." Previous studies have revealed that time-to
      emergence can be altered by mutations in the core clock gene period (per), or by
      altering the length of LD cycles. Since this evidence came from studies on
      genetically manipulated flies, or on flies maintained under LD cycles with
      limited range of periods, inferences that can be drawn are limited. Moreover, the
      extent of shortening or lengthening of time-to-emergence remains yet unknown. In
      order to pursue this further, we assayed time-to-emergence of D. melanogaster
      under 12 different LD cycles as well as in constant light (LL) and constant dark
      conditions (DD). Time-to-emergence in flies occurred earlier under LL than in LD
      cycles and DD. Among the LD cycles, time-to-emergence occurred earlier under T4
      T8, followed by T36-T48, and then T12-T32, suggesting that egg-to-emergence
      duration in flies becomes shorter when the length of LD cycles deviates from 24
      h, bearing a strong positive and a marginally negative correlation with day
      length, for values shorter and longer than 24 h, respectively. These results
      suggest that the extent of mismatch between the period of circadian clocks and
      environmental cycles determines the time-to-emergence in Drosophila.

PMID- 24668962
TI  - Small-molecule inhibitors of AF6 PDZ-mediated protein-protein interactions.
AB  - PDZ (PSD-95, Dlg, ZO-1) domains are ubiquitous interaction modules that are
      involved in many cellular signal transduction pathways. Interference with PDZ
      mediated protein-protein interactions has important implications in disease
      related signaling processes. For this reason, PDZ domains have gained attention
      as potential targets for inhibitor design and, in the long run, drug development.
      Herein we report the development of small molecules to probe the function of the
      PDZ domain from human AF6 (ALL1-fused gene from chromosome 6), which is an
      essential component of cell-cell junctions. These compounds bind to AF6 PDZ with
      substantially higher affinity than the peptide (Ile-Gln-Ser-Val-Glu-Val) derived
      from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6
      Bcr interaction and interfere with epidermal growth factor (EGF)-dependent
      signaling. 

PMID- 24668963
TI  - Outcome of a repair-oriented strategy for the aortic valve in children.
AB  - BACKGROUND: We sought to evaluate the mid-term results of a repair-oriented
      strategy of the aortic valve in children. METHODS: Between February 2007 and
      November 2011, we performed 39 aortic valve repairs in children. Median age and
      weight at surgery were 5.5 years (3 days-18 years) and 16.7 kg (2.7-83.5),
      respectively. A total of 11 (28%) patients had one or more prior surgical or
      interventional cardiologic procedures. Median intensive care unit and hospital
      stay were two (1-96) and five (3-96) days, respectively. Median and cumulative
      follow-up were 12.7 months (15 days-64 months) and 48.9 patient-years,
      respectively. RESULTS: There were 3 (7.7%) early deaths all in patients
      undergoing additional complex cardiac procedures. Two (5.1%) patients required
      early surgical revision. Twenty-six (66%) patients had isolated or mixed aortic
      stenosis. The median gradient reduced from 62.4 (range 16-144) to 17.6 mm Hg
      (range 0-51.8), postoperatively (P = .02). At last follow-up, the median gradient
      remained largely unchanged at 21.1 mm Hg (0-49; P = .02). Twenty-six (66%)
      patients had isolated or mixed aortic valve regurgitation (mild in 8 [20%],
      moderate in 15 [38%], and severe in 6 ([15%] patients). The degree of aortic
      regurgitation improved in all patients with moderate or severe aortic
      regurgitation (P = .04). At last follow-up, two patients had moderate aortic
      regurgitation. Kaplan Meier freedom from reintervention in the survivors was 95%
      at three years. CONCLUSIONS: A repair-oriented strategy for the aortic valve in
      children has satisfactory early and mid-term results and remains a promising
      management option in children with aortic valve disease.

PMID- 24668964
TI  - Heart transplantation in pediatric and congenital heart disease: a single-center
      experience.
AB  - PURPOSE: To describe the indications and outcomes for pediatric patients and
      patients with congenital heart disease (CHD) undergoing heart transplantation
      (HT) in New Zealand. METHODS: A retrospective audit of 253 patients who underwent
      HT from 1987 to end 2012 was undertaken. Thirty-seven patients were subdivided
      into two groups, those aged <18 years--pediatric heart disease (PHD) and those
      with CHD. Six patients aged <18 years were included in both the analyses.
      Demographic and clinical information were collected and outcomes established.
      RESULTS: Overall actuarial survival of 37 patients with PHD or CHD was 92% at one
      year, 85% at five years, and 52% at ten years. The PHD group comprised 22 (8.7%)
      patients, median age 14 years (range 6-17), 14 (64%) male, with cardiomyopathy in
      13, CHD in 6, and rheumatic heart disease in 3. At follow-up, 11 patients had
      died. Actuarial survival was 91% at one year and 79% at five years. Of the four
      patients with a mechanical assist device to bridge, three were transplanted and
      alive at follow-up. The CHD group comprised 21 (8.3%) patients, median age 25
      years (range 6-48) and 19 (90%) were male. At follow-up, three patients had died.
      Actuarial survival was 95% at one year, 94% at five years, and 85% at ten years.
      All five patients with pre-HT Fontan circulation were alive a median of eight
      years following HT. CONCLUSION: Heart transplantation for carefully selected
      pediatric patients and patients with CHD can be successfully performed with
      favorable outcomes in a geographically isolated unit.

PMID- 24668965
TI  - Tachyarrhythmia following Norwood operation: a single-center experience.
AB  - BACKGROUND: The purpose of this study was to characterize tachyarrhythmias in
      children following the Norwood procedure. METHODS: This is a single-center
      retrospective study including all children who underwent stage I Norwood
      procedure (n = 98; January 2003-September 2011). The primary outcome measure is
      the development of tachyarrhythmia during hospitalization after the Norwood
      procedure. Secondary aims include quantification of mortality in patients with
      tachyarrhythmias and evaluation of potential risk factors for the development of
      tachyarrhythmia. RESULTS: Tachyarrhythmia occurred in 33 (34%) of 98 patients.
      The median time to onset of tachyarrhythmia was ten days (0-47 days).
      Tachyarrhythmia conferred no increase in overall mortality (P = .45), including
      operative mortality (P = .37) or interstage mortality (P = 1.00). There was no
      significant difference in the incidence of arrhythmia based on demographic,
      anatomic, or surgical variables, including shunt type (P = .23) except that
      patients with tachyarrhythmias were slightly larger (median weight 3.2 kg) at the
      time of stage I than those without tachyarrhythmia (median weight 2.93 kg; P =
      .02]. The odds of arrhythmia in males were 8.7 times higher than that in females
      (95% confidence interval 2.9-31.3; P < .0001). CONCLUSIONS: Postoperative
      tachyarrhythmia is common, occurring in 34% of patients after the Norwood
      operation. Onset of tachyarrhythmia occurred later after the Norwood operation
      than reported previously, and male gender is a risk factor. Further studies to
      elucidate the etiology and the timing of tachyarrhythmias after the Norwood
      procedure are necessary.

PMID- 24668966
TI  - Surgical treatment of common arterial trunk in patients beyond the first year of
      life.
AB  - BACKGROUND: Common arterial trunk (persistent truncus arteriosus) is a rare
      cardiac defect requiring surgical repair early in life because of the fast
      development of pulmonary vascular obstructive disease. We present our
      institutional experience with patients having common arterial trunk who are
      diagnosed after one year of age. PATIENTS AND METHODS: Between August 2010 and
      May 2013, a total of 1,436 patients were treated for congenital cardiac defects
      at our institution. Common arterial trunk was treated surgically in seven
      patients older than one year of age (three males, four females; age: 13 months to
      5 years, mean: 2.8 +/- 2.04 years). All patients underwent cardiac
      catheterization in order to determine operability. RESULTS: All patients had the
      aortic dominant type of common arterial trunk. The pulmonary vascular resistance
      and Qp/Qs ratio before and after oxygen inhalation were mean 9.04 + 4.2 (range:
      3.8 and 10.7) wood units and 4.67 +/- 2.3 (range: 3 and 6.5) wood units and 3.3 +
      1.8 (range: 1.42 and 5.3) and 4.98 + 2.2 (range: 4 and 6.2), respectively. All
      patients underwent elective primary repair. The ventricular septal defect was
      closed in all patients, five with a nonvalved patch and two with a unidirectional
      check-valved patch. Early postoperatively, patients were sedated,
      hyperventilated, and received nitric oxide for a minimum of 24 hours. There was
      no early or late mortality. The mean length of hospital stay was 9.3 +/- 5.7
      days, and mean duration of follow-up was 214 +/- 59 days. CONCLUSION: Complete
      repair of common arterial trunk in patients older than one year of age is
      feasible in appropriately selected cases. Preoperative cardiac catheterization to
      assess reactivity of the pulmonary vascular bed is important as are appropriate
      strategies for postoperative management. Together, these elements make it
      possible to achieve primary repair with excellent outcomes despite late
      presentation.

PMID- 24668967
TI  - Longitudinal strain and strain rate in patients with hemodynamically significant
      ventricular septal defects.
AB  - BACKGROUND: Patients with significant overcirculation from large ventricular
      septal defects (VSDs) may have altered contractility compared to normal patients.
      METHODS: Patients were enrolled prospectively. Patients were excluded if they
      were acutely ill or over age five. Left ventricular longitudinal strain and
      strain rate were measured in patients with VSDs referred for surgical correction
      and control participants with structurally normal hearts. RESULTS: There was no
      difference in the average longitudinal strain or strain rate of six segments in
      the left ventricle. The mean for both the groups was 19.9% (P = .95). Strain rate
      was 1.5 s(-1) in the patients with a VSD and 1.42 s(-1) in the control group (P =
      .30). The left ventricular end diastolic dimension was significantly larger in
      the group with ventricular defects (z score 1.38 vs -0.37) than the control group
      (P = .000). CONCLUSIONS: The left ventricle end-diastolic dimension in patients
      with ventricular defects was significantly larger, but there was no difference in
      longitudinal strain or strain rate.

PMID- 24668968
TI  - Midterm outcome of primary arterial switch operation beyond six weeks of life in
      children with transposition of great arteries and intact ventricular septum.
AB  - BACKGROUND: We have previously reported our experience in primary arterial switch
      operation (ASO) in children more than six weeks with transposition of great
      arteries and intact ventricular septum (TGA/IVS). The upper age limit for
      performing an ASO in these children is not yet settled and reports regarding
      outcome of ASO in these children are few. In this prospective observational
      study, we report the midterm results of children with TGA-IVS older than six
      weeks undergoing primary ASO. METHODS: A total of 109 children aged more than 6
      weeks with median age of 60 days (range 42-3,000 days), with regressed left
      ventricle underwent primary ASO. Extracorporeal membrane oxygenation was used in
      20% (22 of 109) of them; 90.8% (99 of 109) of children who survived were
      prospectively followed, with a mean follow-up of 28 months (range 18-84 months).
      RESULTS: Two late deaths occurred, and survival in the remainder was estimated to
      be 98% at seven years. The incidence of aortic regurgitation (AR) was found to
      have a decreasing trend with freedom from AR approaching 100% by 34 months. The
      left ventricular shape and function returned to normal within one to three months
      following surgery. None of these children had any rhythm disturbances or evidence
      of myocardial ischemia. CONCLUSIONS: Primary ASO can be safely performed in
      children with regressed ventricle, irrespective of age with encouraging results.
      The midterm results of these children are comparable in terms of survival and
      freedom from complications associated with preserved ventricle.

PMID- 24668969
TI  - Late arterial switch operation for transposition with intact septum.

PMID- 24668970
TI  - Troponin I levels in extracorporeal membrane oxygenation following congenital
      heart surgery.
AB  - BACKGROUND: Correlating postcardiotomy extracorporeal membrane oxygenation (ECMO)
      troponin I (TnI) levels and outcomes. METHODS: Between January 2006 and August
      2010, 34 patients needed postcardiotomy ECMO for low cardiac output. Bailout ECMO
      was required either after unsuccessful weaning from bypass (n = 17, 50%),
      postoperatively from prolonged hemodynamic failure (n = 8, 23.5%), or following
      resuscitation (n = 9, 26.5%). The TnI levels were measured following surgery or
      resuscitation during 10 days and compared between survivors (group I) and non
      survivors (group II). RESULTS: Median support duration was seven days (range: 0
      31). Surgery involving hypoplastic aortic arch repair (Norwood palliation; n = 7,
      20.6%, or biventricular repair; n = 11, 32.4%) led to most ECMO runs. Successful
      weaning from ECMO and hospital survival were 76.5% and 50%, respectively. In
      group I, peak TnI levels were reached by 24 hours postoperatively, comparable to
      levels in group II (36 +/- 34 vs 49 +/- 38 ng/mL; P = .98). However, in group II,
      TnI levels formed a plateau by the second postoperative day, whereas group I
      showed a steep decline in TnI levels, suggesting myocardial recovery (P = .028).
      All patients (n = 4) who reached or maintained peak TnI levels at 48 hours died.
      On days 8, 9 and 10, TnI levels were significantly higher in group II (P = .024,
      .019, and .013, respectively). CONCLUSIONS: Postcardiotomy ECMO was most commonly
      required after aortic arch repair. In the absence of ongoing myocardial insult
      due to ECMO hardware issues, coronary insufficiency or residual lesions, plateau
      TnI levels at 48 hours may seem to indicate an unfavorable outcome due to
      irreversible myocardial damage.

PMID- 24668971
TI  - Intermediate-term results of extracorporeal membrane oxygenation support
      following congenital heart surgery.
AB  - BACKGROUND: Although there are considerable data regarding in-hospital results of
      congenital heart surgery (CHS) patients requiring postoperative extracorporeal
      membrane oxygenation (ECMO) support, there is limited information on intermediate
      term outcomes. METHODS: A single-institution retrospective review of 25
      consecutive postoperative CHS patients who required ECMO and survived to hospital
      discharge between January 2003 and June 2008. Survival was estimated by the
      Kaplan-Meier method. RESULTS: At a median follow-up of 3.3 years (interquartile
      range: 1.2-5.9 years), there was one death which occurred at six months
      postsurgery. Kaplan-Meier-estimated survival at three years was 95% (95%
      confidence interval: 90%-100%). Indications for ECMO included extracorporeal
      cardiopulmonary resuscitation (48%), systemic hypoxia (4%), postoperative low
      cardiac output syndrome (28%), and intraoperative failure to wean off
      cardiopulmonary bypass (20%). Following ECMO support, 65% of patients had
      unplanned cardiac reinterventions (three requiring operative interventions, six
      requiring percutaneous interventions, and four requiring both), and 47% of
      patients required unplanned hospitalizations. In all, 29% of patients developed
      neurological deficits and 12% of patients developed chronic respiratory failure.
      No patients developed renal failure. Overall, systemic ventricular (SV) function
      normalized in 83% of patients, whereas 17% of patients had persistent mild-to
      moderate SV dysfunction. CONCLUSIONS: Intermediate-term patient survival of ECMO
      following CHS is encouraging. However, neurological impairment and unplanned
      cardiac reinterventions remain significant concerns. Further delineation of risk
      factors to improve patient outcomes is warranted.

PMID- 24668972
TI  - Transposition of the great arteries--outcomes and time interval of early neonatal
      repair.
AB  - BACKGROUND: This study evaluates the relationship of morbidity and resource
      utilization with the timing of early neonatal repair of transposition of the
      great arteries and intact ventricular septum (d-TGA/IVS). METHODS: All patients
      with d-TGA/IVS who underwent arterial switch in the first 14 days of life,
      between January 2000 and May 2011, were reviewed. Patients undergoing repair at
      <= 4 days of age were categorized as group I, 5 to 7 days as group II, and 8 to
      14 days as group III. Outcomes included mortality, morbidity, and resource
      utilization. RESULTS: Hospital survival was 69 (98.6%) of 70. The length of stay
      (LOS) and total charges were lowest in group I--15.5 days compared to group II-
      18.0 days and group III--23.5 days (P = .005); group I--US$128,219 compared to
      group II--US$141,729 and group III--US$217,427 (P = .0006). Using regression
      analysis to account for potentially confounding effects of multiple variables and
      treating time as a continuous variable demonstrated that age at surgery was
      significantly associated with total LOS (P = .029), hospital charges (P = .029)
      and intensive care unit charges (P = .002). Younger age at repair was not
      associated with worse outcomes for any measure of morbidity. CONCLUSIONS: Earlier
      repair of d-TGA/IVS was associated with decreased resource utilization and no
      detriment to clinical outcomes. Further analysis based on a larger cohort of
      patients is needed to verify these results that have important implications for
      improving the value of care.

PMID- 24668973
TI  - Survey of nongovernmental organizations providing pediatric cardiovascular care
      in low- and middle-income countries.
AB  - BACKGROUND: Nearly 90% of the children with heart disease in low- and middle
      income countries (LMICs) cannot access cardiovascular (CV) services. Limitations
      include inadequate financial, human, and infrastructure resources.
      Nongovernmental organizations (NGOs) have played crucial roles in providing
      clinical services and infrastructure supports to LMICs CV programs; however,
      these outreach efforts are dispersed, inadequate, and lack coordination. METHODS:
      A survey was sent to members of the World Society for Pediatric and Congenital
      Heart Society and PediHeart. RESULTS: A clearinghouse was created to provide
      information on NGO structures, geographic reach, and scope of services. The
      survey identified 80 NGOs supporting CV programs in 92 LMICs. The largest
      outreach efforts were in South and Central America (42%), followed by Africa
      (18%), Europe (17%), Asia (17%), and Asia-Western Pacific (6%). Most NGOs (51%)
      supported two to five outreach missions per year. The majority (87%) of NGOs
      provided education, diagnostics, and surgical or catheter-based interventions.
      Working jointly with LMIC partners, 59% of the NGOs performed operations in
      children and infants; 41% performed nonbypass neonatal operations. Approximately
      a quarter (26%) reported that partner sites do not perform interventions in
      between missions. CONCLUSIONS: Disparity and inadequacy in pediatric CV services
      remain an important problem for LMICs. A global consensus and coordinated efforts
      are needed to guide strategies on the development of regional centers of
      excellence, a global outcome database, and a CV program registry. Future efforts
      should be held accountable for impacts such as growth in the number of
      independent LMIC programs as well as reduction in mortality and patient waiting
      lists.

PMID- 24668975
TI  - Linking the congenital heart surgery databases of the Society of Thoracic
      Surgeons and the Congenital Heart Surgeons' Society: part 2--lessons learned and
      implications.
AB  - PURPOSE: A link has been created between the Society of Thoracic Surgeons
      Congenital Heart Surgery Database (STS-CHSD) and the Congenital Heart Surgeons'
      Society Database (CHSS-D). Five matrices have been created that facilitate the
      automated identification of patients who are potentially eligible for the five
      active CHSS studies using the STS-CHSD. These matrices are now used to (1)
      estimate the denominator of patients eligible for CHSS studies and (2) compare
      "eligible and enrolled patients" to "potentially eligible and not enrolled
      patients" to assess the generalizability of CHSS studies. METHODS: The matrices
      were applied to 40 consenting institutions that participate in both the STS-CHSD
      and the CHSS to (1) estimate the denominator of patients that are potentially
      eligible for CHSS studies, (2) estimate the completeness of enrollment of
      patients eligible for CHSS studies among all CHSS sites, (3) estimate the
      completeness of enrollment of patients eligible for CHSS studies among those CHSS
      institutions participating in each CHSS cohort study, and (4) compare "eligible
      and enrolled patients" to "potentially eligible and not enrolled patients" to
      assess the generalizability of CHSS studies. The matrices were applied to all
      participants in the STS-CHSD to identify patients who underwent frequently
      performed operations and compare "eligible and enrolled patients" to "potentially
      eligible and not enrolled patients" in following five domains: (1) age at
      surgery, (2) gender, (3) race, (4) discharge mortality, and (5) postoperative
      length of stay. Completeness of enrollment was defined as the number of actually
      enrolled patients divided by the number of patients identified as being
      potentially eligible for enrollment. RESULTS: For the CHSS Critical Left
      Ventricular Outflow Tract Study (LVOTO) study, for the Norwood procedure,
      completeness of enrollment at centers actively participating in the LVOTO study
      was 34%. For the Norwood operation, discharge mortality was 15% among 227
      enrolled patients and 16% among 1768 nonenrolled potentially eligible patients
      from the 40 consenting institutions. Median postoperative length of stay was 31
      days and 26 days for these enrolled and nonenrolled patients. For the CHSS
      anomalous aortic origin of a coronary artery (AAOCA) study, for AAOCA repair,
      completeness of enrollment at centers actively participating in the AAOCA study
      was 40%. CONCLUSION: Determination of the denominator of patients eligible for
      CHSS studies and comparison of "eligible and enrolled patients" to "potentially
      eligible and not enrolled patients" provides an estimate of the extent to which
      patients in CHSS studies are representative of the overall population of eligible
      patients; however, opportunities exist to improve enrollment.

PMID- 24668977
TI  - The expanding indications for the Lecompte maneuver.
AB  - Since the anterior translocation of the pulmonary arteries in relation to the
      aorta (Lecompte maneuver) was first described in 1981, its indications have
      continued to expand. In this review, we discuss the physiological basis and the
      expanding indications for this maneuver. 

PMID- 24668976
TI  - Pediatric applications of surgical patch angioplasty of the main coronary trunks.
AB  - OBJECTIVES: Obstruction of the main coronary trunks, although rare among the
      general pediatric population, remains an important complication of the arterial
      switch operation (ASO). Surgical patch angioplasty (SPA) is a technique whereby
      myocardial revascularization is achieved through direct ostial enlargement,
      restoring antegrade coronary flow, avoiding competitive flow, and preserving
      conduit material. This study investigates the indications, techniques, and
      outcomes of SPA in the pediatric population. METHODS: A systematic literature
      review identified 15 studies incorporating 92 patients. The primary outcome of
      interest was 30-day mortality. Secondary outcomes included 30-day major adverse
      cardiac and cerebrovascular events, mortality at last follow-up, reintervention
      rate, symptomatic status, angiographic patency, and myocardial perfusion status
      at last follow-up. RESULTS: The SPA was most frequently performed to treat ostial
      occlusion as a complication of the ASO (73.9%). Of the procedures, 77.2% involved
      the left main stem, 8.7% the left anterior descending artery, and 14.1% the right
      coronary artery. Saphenous vein was the commonest patch type (60.9%) followed by
      autologous pericardium (23.9%). Of the procedures, 96.7% were considered
      successful with an uneventful postoperative recovery. Overall hospital mortality
      was 2.2%. At a mean of 39 months of follow-up, 84.8% of the patients were
      asymptomatic, 51.1% of the repairs were angiographically patent, 9.8% had
      myocardial perfusion defects, and 6.5% required repeat revascularization.
      CONCLUSION: Current evidence suggests that SPA shows encouraging outcomes in a
      pediatric population and, with increasing experience, may provide a definitive
      solution to coronary artery occlusion.

PMID- 24668974
TI  - Linking the congenital heart surgery databases of the Society of Thoracic
      Surgeons and the Congenital Heart Surgeons' Society: part 1--rationale and
      methodology.
AB  - PURPOSE: The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS
      CHSD) is the largest Registry in the world of patients who have undergone
      congenital and pediatric cardiac surgical operations. The Congenital Heart
      Surgeons' Society Database (CHSS-D) is an Academic Database designed for
      specialized detailed analyses of specific congenital cardiac malformations and
      related treatment strategies. The goal of this project was to create a link
      between the STS-CHSD and the CHSS-D in order to facilitate studies not possible
      using either individual database alone and to help identify patients who are
      potentially eligible for enrollment in CHSS studies. METHODS: Centers were
      classified on the basis of participation in the STS-CHSD, the CHSS-D, or both.
      Five matrices, based on CHSS inclusionary criteria and STS-CHSD codes, were
      created to facilitate the automated identification of patients in the STS-CHSD
      who meet eligibility criteria for the five active CHSS studies. The matrices were
      evaluated with a manual adjudication process and were iteratively refined. The
      sensitivity and specificity of the original matrices and the refined matrices
      were assessed. RESULTS: In January 2012, a total of 100 centers participated in
      the STS-CHSD and 74 centers participated in the CHSS. A total of 70 centers
      participate in both and 40 of these 70 agreed to participate in this linkage
      project. The manual adjudication process and the refinement of the matrices
      resulted in an increase in the sensitivity of the matrices from 93% to 100% and
      an increase in the specificity of the matrices from 94% to 98%. CONCLUSION:
      Matrices were created to facilitate the automated identification of patients
      potentially eligible for the five active CHSS studies using the STS-CHSD. These
      matrices have a sensitivity of 100% and a specificity of 98%. In addition to
      facilitating identification of patients potentially eligible for enrollment in
      CHSS studies, these matrices will allow (1) estimation of the denominator of
      patients potentially eligible for CHSS studies and (2) comparison of eligible and
      enrolled patients to potentially eligible and not enrolled patients to assess the
      generalizability of CHSS studies.

PMID- 24668978
TI  - The "tube-in-tube" circuit: a new method for delivering cold blood cardioplegia
      in neonates and small infants.
AB  - PURPOSE: To conceive a method to deliver cold blood cardioplegia in neonates and
      young infants. DESCRIPTION: The "tube-in-tube" circuit consists of a 3-mm line
      (bloodline) which is inserted inside a 1/2 -in tube where cold water flows
      continuously (waterline). This circuit includes a filling volume of 18 mL of
      static prime and 15 mL for the collecting line (pump raceway). Several
      temperature samples were taken at different blood flows from 20 to 100 mL/min.
      EVALUATION: Temperatures (in  degrees C) at the needle tip were significantly
      lower when using the tube-in-tube cooling circuit if compared to standard
      cardioplegia circuit at flows up to 60 mL/min. CONCLUSIONS: The tube-in-tube
      circuit proved to be an effective strategy for low-flow cardioplegia delivery
      (<60 ml/min), which is particularly useful in neonates and young infants; the
      lower is the flow, the better is the cooling effect on the cardioplegia.

PMID- 24668979
TI  - Modified primary sutureless repair technique of total anomalous pulmonary venous
      connection.
AB  - Surgical correction of total anomalous pulmonary venous connection is associated
      with an important risk of postrepair pulmonary vein obstruction. Primary
      sutureless anastomosis at the time of initial surgical repair might mitigate that
      risk. A simplified primary sutureless technique is described in this report. 

PMID- 24668980
TI  - Right pulmonary artery to left atrial fistula in a neonate: case report and
      review of the literature.
AB  - A communication between the right pulmonary artery (RPA) and the left atrium is a
      rare congenital anomaly that presents with cyanosis and heart failure. We
      describe the surgical repair of an RPA to left atrial fistula using
      cardiopulmonary bypass in a neonate. Advanced imaging (computed tomography scan)
      guided the surgical approach. Although previous reports have associated a patent
      ductus arteriosus with high neonatal mortality, in our case, the ductus
      arteriosus was actually important for maintaining enough total pulmonary blood
      flow. 

PMID- 24668981
TI  - Ethical dilemma: offering short-term extracorporeal membrane oxygenation support
      for terminally ill children who are not candidates for long-term mechanical
      circulatory support or heart transplantation.
AB  - The use of extracorporeal membrane oxygenation (ECMO) in terminally ill pediatric
      patients who are not candidates for long-term mechanical circulatory support or
      heart transplantation requires careful deliberation. We present the case of a 16
      year-old female with a relapse of acute lymphoid leukemia and acute-on-chronic
      cardiomyopathy who received short-term ECMO therapy. In addition, we highlight
      several ethical considerations that were crucial to this patient's family
      centered care and demonstrate that this therapy can be accomplished in a manner
      that respects patient autonomy and family wishes. 

PMID- 24668982
TI  - Transmyocardial migration of a temporary epicardial pacing wire: a pediatric case
      report.
AB  - Transmyocardial migration of a retained temporary epicardial pacing wire has been
      rarely reported in adult patients after heart surgery. We present the case of a
      child in whom a temporary epicardial pacing wire was discovered incidentally in
      the right ventricular outflow tract one year after surgical repair of congenital
      heart disease. The pacing wire was subsequently extracted using the snare method
      during cardiac catheterization. Clinicians caring for patients after congenital
      heart surgery should be aware of this uncommon though potentially life
      threatening complication. 

PMID- 24668983
TI  - Cortriatriatum with classical Raghib complex: a rare anatomic association.
AB  - Cortriatriatum with Raghib's complex is a rarely reported entity. An 18-month-old
      baby who presented with tachypnea and cyanosis was diagnosed to have
      cortriatriatum sinistrum along with a persistant left superior caval vein
      draining to the left atrium through an unroofed coronary sinus. The child
      underwent successful surgical correction with excision of the cortriatriatum and
      baffling of the left superior caval vein to the right atrium. 

PMID- 24668984
TI  - Divided left atrium--or triatrial heart?

PMID- 24668985
TI  - Hypoplastic left heart syndrome with dextrocardia and situs solitus.
AB  - Hypoplastic left heart syndrome with dextrocardia and situs solitus is a very
      rare condition. We describe a 3.5-year-old male child with this constellation who
      underwent multistage repair and a successful extracardiac Fontan operation in our
      hospital. 

PMID- 24668986
TI  - Avoiding coronary injury in congenital heart surgery by laser-assisted
      indocyanine green dye imaging.
AB  - Many patients with congenital heart disease require a staged surgical approach to
      achieve optimum circulation. During repeat operations, coronary anatomy can be
      difficult to ascertain because of epicardial scarring or underlying anomalous
      coronary anatomy. Uncertainty about coronary artery location increases the risk
      of reoperation. Having real-time data of coronary anatomy improves intraoperative
      decision making and enhances patient safety. We describe four patients undergoing
      reoperation with the aid of laser-assisted indocyanine green dye imaging to
      provide real-time data about coronary artery anatomy intraoperatively, thus
      helping the surgeon to prevent coronary artery injury. 

PMID- 24668987
TI  - A rare congenital cardiac anomaly in adulthood: tetralogy of Fallot with absent
      pulmonary valve syndrome.
AB  - In approximately 3% to 6% of the patients with tetralogy of Fallot (TOF), the
      pulmonary valve leaflets are absent or only a rudimentary ridge of tissue is
      present. Some infants with the severe form of this syndrome die early during the
      newborn period due to severe respiratory distress, feeding intolerance, or
      cardiovascular compromise. Survival to adulthood of this combination is extremely
      unusual. In this article, we presented a case who was diagnosed in adult age with
      TOF having absent pulmonary valve syndrome. The patient with these findings
      underwent surgery, and complete repair was performed. Clinical symptoms resolved
      after surgery. 

PMID- 24668988
TI  - Heart failure due to "disappearing" aortic valve in hypoplastic left heart
      syndrome.
AB  - We present the unusual case of a "disappearing" aortic valve in an infant with
      hypoplastic left heart syndrome (mitral and aortic stenosis) that underwent
      Norwood palliation at birth and subsequently a Glenn operation. Angiographic
      images at the time of operation showed no apparent insufficiency of the native
      aortic valve. Over the course of 14 months following operation, the patient
      developed significant cardiomegaly with a workup revealing severe native aortic
      valve insufficiency. Following orthotopic heart transplantation, examination of
      the explanted heart revealed a complete absence of native aortic valve leaflets. 

PMID- 24668989
TI  - Hybrid perventricular pulmonary valve perforation and right ventricular outflow
      stent placement: a case report of a premature, 1.3-kg neonate with tetralogy of
      Fallot and pulmonary atresia.
AB  - Premature infants with very low birth weight with tetralogy of Fallot and
      pulmonary atresia (TOF/PA) have been shown to have poor surgical outcomes.
      Palliating these patients by stenting the right ventricular outflow tract (RVOT)
      has been shown to be safe and effective. In patients with very low birth weight,
      a hybrid perventricular approach offers the ability to perform pulmonary valve
      perforation and RVOT stent placement while avoiding cardiopulmonary bypass and
      femoral vessel complications in the neonatal period. We present a hybrid
      perventricular treatment of a patient weighing 1.3 kg with TOF/PA. 

PMID- 24668990
TI  - Left ventricular thrombus formation after repair of anomalous left coronary
      artery from the pulmonary artery.
AB  - Although thrombus formation following myocardial infarction in adults is well
      known, intracardiac thrombosis in children is uncommon. We report the case of a
      large left ventricular thrombus in an infant with ischemic cardiomyopathy
      secondary to anomalous origin of the left coronary artery from the pulmonary
      artery. Given its mobility and protrusion across the aortic valve, the patient
      underwent urgent thrombus removal through a transaortic approach. There were no
      embolic or neurologic complications. This case highlights that thrombectomy may
      be performed safely and successfully in critically ill pediatric patients. 

PMID- 24668991
TI  - Hyperbilirubinemia complicating plasma-free hemoglobin and antifactor Xa level
      monitoring on venovenous extracorporeal membrane oxygenation.
AB  - Optical spectrophotometric methods are used to detect both plasma-free hemoglobin
      and antifactor Xa level, so hyperbilirubinemia can interfere with the measurement
      of both the monitoring laboratory tests for extracorporeal membrane oxygenation
      (ECMO) due to similar absorbance wavelengths. We present a seven-year-old child
      with acute respiratory failure on venovenous ECMO who developed an acute increase
      in plasma-free hemoglobin and undetectable antifactor Xa level due to acute
      hyperbilirubinemia from hepatic dysfunction related to antifungal therapy. 

PMID- 24668992
TI  - Aneurysmal dilatation without distal obstruction: a rare complication of valved
      bovine jugular vein conduit.
AB  - Valved bovine jugular vein (Contegra) conduit is considered a suitable choice for
      pediatric population with congenital heart defect requiring right ventricle to
      main pulmonary artery connection. Intermediate follow-up studies have shown the
      propensity of developing distal conduit stenosis and valve thrombosis. We present
      a rare case of aneurysmal dilatation of the conduit leading to valve failure
      requiring conduit explantation. 

PMID- 24668993
TI  - The politics of intraoperative transesophageal echocardiography.

PMID- 24668994
TI  - Anatomically corrected malposition or double outlet right ventricle?

PMID- 24668995
TI  - Reply: Anatomically corrected malposition or double outlet right ventricle?

PMID- 24668996
TI  - Surgical management of short bowel syndrome.
AB  - For patients with short bowel syndrome (SBS), surgery can play an important role
      in preventing, mitigating, and, in some cases, reversing intestinal failure (IF).
      During intestinal resection, bowel length should be conserved to the fullest
      extent possible to avoid dependence on parenteral nutrition (PN). Bowel salvage
      may be improved by initially preserving tissue of questionable viability and
      later reevaluating during "second-look" procedures. Once the patient is
      stabilized, ostomy reversal and recruitment of distal unused bowel should be
      prioritized whenever feasible. Following progression to IF, surgical management
      of SBS depends on the symptoms and anatomical characteristics of the individual
      patient. For carefully selected patients with rapid intestinal transit and
      dilated bowel, longitudinal intestinal lengthening and tailoring (LILT) and
      serial transverse enteroplasty (STEP) procedures may provide benefit. Outcomes
      following STEP and LILT are generally similar, and the choice between these
      procedures may rest on surgeon preference. For patients with rapid intestinal
      transit in the absence of bowel dilation, segmental reversal of the small bowel
      may reduce PN requirements. Intestinal transplantation is the standard of care
      for patients in whom intestinal rehabilitation attempts have failed and who are
      at risk of life-threatening complications of PN. Because patients awaiting
      isolated intestine transplant show increased survival compared with patients
      awaiting combined intestine-liver transplant, early referral of appropriate
      patients, before the development of advanced liver disease, is critical to
      enhancing patient outcomes. 

PMID- 24668997
TI  - Impact of Disease Activity on Resting Energy Expenditure and Body Composition in
      Adult Crohn's Disease: A Prospective Longitudinal Assessment.
AB  - BACKGROUND: There is controversy about nutrition status and calorie needs during
      phases of active versus inactive adult Crohn's disease (CD). Results have been
      reported in cross-sectional studies, but longitudinal data are unavailable. Our
      aim was to explore whether disease activity had an impact on resting energy
      expenditure (REE) and body composition in adult patients with CD. MATERIALS AND
      METHODS: Adult patients were studied on 2 occasions with active and inactive CD.
      REE was measured by indirect calorimetry. Body composition was estimated from
      bioelectrical impedance analysis. Disease activity was measured using the Crohn's
      Disease Activity Index (CDAI). Regression analyses of REE with CDAI score, C
      reactive protein, and erythrocyte sedimentation rate were also performed.
      RESULTS: Seventy-five patients were included. Patients with active CD had
      increased REE/body weight compared with patients with inactive disease (28.8 +/-
      5.4 vs 25.9 +/- 4.3 kcal/kg, P < .001). Disease behavior and location, but not
      sex, had an impact on REE/body weight. Body mass index was lower in active
      disease than in remission (17.4 +/- 3.0 vs 18.1 +/- 2.6 kg/m(2), P = .010). Body
      composition was not affected by disease behavior or location. CONCLUSION:
      Patients with remission had a better nutrition status and decreased REE compared
      with those with active CD. REE could also be affected by disease location and
      behavior.

PMID- 24668998
TI  - Aging techniques for deep vein thrombosis: a systematic review.
AB  - Deep vein thrombosis is common with an incidence of 1 in 1000. Acute thrombus
      removal for extensive proximal deep vein thrombosis using catheter-directed
      techniques highlights the need for accurate assessment of thrombus age. This
      systematic review summarises experimental and clinical evidence of imaging
      techniques for aging deep vein thrombosis. Ultrasound elastography and magnetic
      resonance imaging were highlighted as the most studied imaging modalities.
      Elastography was shown to distinguish between acute and chronic clots, despite
      demonstrating difficulty in accurate aging of clots older than 10 days in rat
      models. Elastography is noted as a feasible adjunct to current first-line imaging
      for deep vein thrombosis using duplex ultrasonography. Combinations of magnetic
      resonance imaging techniques can identify acute, sub-acute and chronic thrombi
      using endogenous contrast agents and provide objective standardisation of the
      diagnostic process, with reduced onus upon operator dependency. Further
      validation is required of these novel imaging techniques prior to clinical
      implementation for deep vein thrombosis aging. 

PMID- 24668999
TI  - Bariatric amputee: A growing problem?
AB  - BACKGROUND: This study reviewed prevalence of patients with lower limb
      amputations with above normal weight profile, with body mass index over 25, in
      seven disablement services centres managing their amputee rehabilitation in the
      United Kingdom. OBJECTIVES: To review two clinical standards of practice in
      amputee rehabilitation. Ambulant lower limb amputees should have their body
      weight recorded on an electronic information system, with identification of
      cohort with body weight >100 kg. Lower limb amputees to be provided with suitable
      weight-rated prosthesis. STUDY DESIGN: Observational study of clinical practice.
      METHODS: Data were collected from the Clinical Information Management Systems.
      Inclusion criteria--subjects were ambulant prosthetic users with some prosthetic
      intervention in the last 5 years and had at least one lower limb amputation.
      RESULTS: In 96% of patients, the weight record profile was maintained. In
      addition, 86% were under 100 kg, which is the most common weight limit of
      prosthetic componentry. Of 15,204 amputation levels, there were 1830 transfemoral
      and transtibial sites in users with body weight over 100 kg. In 60 cases, the
      prosthetic limb build was rated to be below the user body weight. CONCLUSIONS: In
      96% of our patients, body weight was documented, and in 97%, the prosthetic limb
      builds were within stated body weight limits, but this may not be the case in all
      the other disablement services centres in the United Kingdom. Also, the incidence
      of obesity in the United Kingdom is a growing problem, and the health issues
      associated with obesity are further compounded in the amputee population.
      CLINICAL RELEVANCE: Prosthetic componentry has distinct weight limits which must
      be considered during prescription. As people with amputation approach the limits
      of specific components, clinicians are faced with the challenge of continued
      provision in a safe and suitable manner. This article reviews the amputee
      population and the current national profile to consider trends in provision and
      the incidence of these challenges.

PMID- 24669000
TI  - Response: Letter to the Editor.

PMID- 24669001
TI  - Developing prescribing guidelines for microprocessor-controlled prosthetic knees
      in the South East England.
AB  - BACKGROUND AND AIM: Microprocessor-controlled prosthetic knees have gained
      increasing popularity over the last decade. Research supports their provision to
      address specific problems or to achieve certain rehabilitation goals. However,
      there are yet no agreed protocols or prescribing criteria to assist clinicians in
      the identification and appropriate selection of suitable users. The aim is to
      reach professionals' agreement on specific prescribing guidelines for
      microprocessor-controlled prosthetic knees. TECHNIQUE: The study involved
      multidisciplinary teams from the Inter Regional Prosthetic Audit Group,
      representing nine Prosthetic Rehabilitation Centres in the South East England
      region. We used the Delphi technique with a total of three rounds to reach
      professionals' agreement. DISCUSSION: The prescribing guidelines were agreed and
      will be reviewed and updated depending on new research evidence and technical
      advances. CLINICAL RELEVANCE: This project is highly useful for professionals in
      a clinic setting to aid in appropriate patient selection and to justify the cost
      of prescribing microprocessor-controlled prosthetic knees.

PMID- 24669002
TI  - Feasibility of cerebral blood flow and oxygenation monitoring by continuous
      transcranial Doppler combined with cerebral oximetry in a patient with refractory
      cardiac arrest treated by extracorporeal life support.
AB  - The adequacy of cerebral blood flow and the level of regional oxygen saturation
      during CPR and early post-resuscitation phases assuring favorable neurological
      outcome are not known. We demonstrate the feasibility of cerebral blood flow and
      oxygenation monitoring by a continuous transcranial Doppler combined with
      cerebral oximetry in a patient with refractory cardiac arrest treated by
      extracorporeal life support. 

PMID- 24669003
TI  - The role of awareness in attitude formation through evaluative conditioning.
AB  - This article provides a review of past and contemporary debates regarding the
      role of awareness in attitude formation through evaluative conditioning (EC),
      that is, by repeatedly pairing a stimulus with other stimuli of positive or
      negative valence. Because EC is considered the most prototypical method to form
      and change the network of evaluative associations in memory, the role of
      awareness in this effect is critical to the question of whether attitudes may be
      formed and changed through dual processes. We analyze the reasons why there has
      been so much discussion and disagreement regarding the role of awareness, review
      past and contemporary methodologies and their limitations, discuss the role of
      mental processes and conditioning procedures, and identify promising directions
      for future research in this area. 

PMID- 24669004
TI  - Nonruminant Nutrition Symposium: Breaking the mold -formulating monogastric diets
      without traditional ingredients.

PMID- 24669005
TI  - Ruminant Nutrition Symposium: Advancements in enhancing cell wall digestibility
      and its contribution to improve ruminant production.

PMID- 24669006
TI  - Meat Science and Muscle Biology Symposium: Preharvest factors affecting the
      prevalence of pathogens in livestock and meat.

PMID- 24669007
TI  - Meat Science and Muscle Biology Symposium: Ecological and dietary impactors of
      foodborne pathogens and methods to reduce fecal shedding in cattle.
AB  - Pathogenic bacteria can live asymptomatically within and on cattle and can enter
      the food chain but also can be transmitted to humans by fecal or direct animal
      contact. Reducing pathogenic bacterial incidence and populations within live
      cattle represents an important step in improving food safety. A broad range of
      preslaughter intervention strategies are being developed, which can be loosely
      classified as 1) directly antipathogen strategies, 2) competitive enhancement
      strategies (that use the microbiome's competitive nature against pathogens), and
      3) animal management strategies. Included within these broad categories are such
      diverse methods as vaccination against foodborne pathogens, probiotics and
      prebiotics, bacterial viruses (i.e., bacteriophages), sodium chlorate feeding,
      and dietary and management changes that specifically alter the microbiome. The
      simultaneous application of 1 or more preharvest strategies has the potential to
      reduce human foodborne illnesses by erecting multiple hurdles preventing entry
      into humans. However, economic factors that govern producer profitability must be
      kept in mind while improving food safety. 

PMID- 24669009
TI  - Development and external validation of a nomogram for overall survival after
      curative resection in serosa-negative, locally advanced gastric cancer.
AB  - BACKGROUND: Few nomograms can predict overall survival (OS) after curative
      resection of advanced gastric cancer (AGC), and these nomograms were developed
      using data from only a few large centers over a long time period. The aim of this
      study was to develop and externally validate an elaborative nomogram that
      predicts 5-year OS after curative resection for serosa-negative, locally AGC
      using a large amount of data from multiple centers in Japan over a short time
      period (2001-2003). PATIENTS AND METHODS: Of 39 859 patients who underwent
      surgery for gastric cancer between 2001 and 2003 at multiple centers in Japan, we
      retrospectively analyzed 5196 patients with serosa-negative AGC who underwent
      Resection A according to the 13th Japanese Classification of Gastric Carcinoma.
      The data of 3085 patients who underwent surgery from 2001 to 2002 were used as a
      training set for the construction of a nomogram and Web software. The data of
      2111 patients who underwent surgery in 2003 were used as an external validation
      set. RESULTS: Age at operation, gender, tumor size and location, macroscopic
      type, histological type, depth of invasion, number of positive and examined lymph
      nodes, and lymphovascular invasion, but not the extent of lymphadenectomy, were
      associated with OS. Discrimination of the developed nomogram was superior to that
      of the TNM classification (concordance indices of 0.68 versus 0.61; P < 0.001).
      Moreover, calibration was accurate. CONCLUSIONS: We have developed and externally
      validated an elaborative nomogram that predicts the 5-year OS of postoperative
      serosa-negative AGC. This nomogram would be helpful in the assessment of
      individual risks and in the consideration of additional therapy in clinical
      practice, and we have created freely available Web software to more easily and
      quickly predict OS and to draw a survival curve for these purposes.

PMID- 24669010
TI  - Randomised phase III study of neoadjuvant chemotherapy with methotrexate,
      doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared
      with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical
      Oncology Group Study JCOG0209.
AB  - BACKGROUND: This study aimed to determine the clinical benefit of neoadjuvant
      methotrexate, doxorubicin, vinblastine, and cisplatin (MVAC) in patients with
      muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. PATIENTS
      AND METHODS: Patients with MIBC (T2-4aN0M0) were randomised to receive two cycles
      of neoadjuvant MVAC followed by radical cystectomy (NAC arm) or radical
      cystectomy alone (RC arm). The primary end point was overall survival (OS).
      Secondary end points were progression-free survival, surgery-related
      complications, adverse events during chemotherapy, proportion with no residual
      tumour in the cystectomy specimens, and quality of life. To detect an improvement
      in 5-year OS from 45% in the RC arm to 57% in the NAC arm with 80% power, 176
      events were required per arm. RESULTS: Patients (N = 130) were randomly assigned
      to the RC arm (N = 66) and the NAC arm (N = 64). The patient registration was
      terminated before reaching the initially planned number of patients because of
      slow accrual. At the second interim analysis just after the early stoppage of
      patient accrual, the Data and Safety Monitoring Committee recommended early
      publication of the results because the trial did not have enough power to draw a
      confirmatory conclusion. OS of the NAC arm was better than that of the RC arm,
      although the difference was not statistically significant [hazard ratio 0.65,
      multiplicity adjusted 99.99% confidence interval 0.19-2.18, one-sided P = 0.07].
      In the NAC arm and the RC arm, 34% and 9% of the patients had pT0, respectively
      (P < 0.01). In subgroup analyses, OS in almost all subgroups was in favour of
      NAC. CONCLUSIONS: This trial showed a significantly increased pT0 proportion and
      favourable OS of patients who received neoadjuvant MVAC. NAC with MVAC can still
      be considered promising as a standard treatment. UMIN CLINICAL TRIALS REGISTRY
      IDENTIFIER: C000000093.

PMID- 24669011
TI  - Survival of women with inflammatory breast cancer: a large population-based
      study.
AB  - BACKGROUND: Our group has previously reported that women with inflammatory breast
      cancer (IBC) continue to have worse outcome compared with those with non-IBC. We
      undertook this population-based study to see if there have been improvements in
      survival among women with stage III IBC, over time. PATIENT AND METHODS: We
      searched the Surveillance, Epidemiology and End Results Registry to identify
      female patients diagnosed with stage III IBC between 1990 and 2010. Patients were
      divided into four groups according to year of diagnosis: 1990-1995, 1996-2000,
      2001-2005, and 2006-2010. Breast cancer-specific survival (BCSS) was estimated
      using the Kaplan-Meier method and compared across groups using the log-rank test.
      Cox models were then fit to determine the association of year of diagnosis and
      BCSS after adjusting for patient and tumor characteristics. RESULTS: A total of
      7679 patients with IBC were identified of whom 1084 patients (14.1%) were
      diagnosed between 1990 and 1995, 1614 patients (21.0%) between 1996 and 2000,
      2683 patients (34.9%) between 2001 and 2005, and 2298 patients (29.9%) between
      2006 and 2010. The 2-year BCSS for the whole cohort was 71%. Two-year BCSS were
      62%, 67%, 72%, and 76% for patients diagnosed between 1990-1995, 1996-2000, 2001
      2005, and 2006-2010, respectively (P < 0.0001). In the multivariable analysis,
      increasing year of diagnosis (modeled as a continuous variable) was associated
      with decreasing risks of death from breast cancer (HR = 0.98, 95% confidence
      interval 0.97-0.99, P < 0.0001). CONCLUSION: There has been a significant
      improvement in survival of patients diagnosed with IBC over a two-decade time
      span in this large population-based study. This suggests that therapeutic
      strategies researched and evolved in the context of non-IBC have also had a
      positive impact in women with IBC.

PMID- 24669012
TI  - Comparative analysis of breast cancer mortality following mammography screening
      in Denmark and Norway.
AB  - BACKGROUND: Denmark and Norway are the best countries to study effects of
      mammography screening, because they are the only countries with stepwise
      introduction of nationwide mammography screening, enabling comparative
      effectiveness studies of high quality. Although Denmark and Norway are countries
      with similar populations and health care systems, reported reductions in breast
      cancer mortality (incidence-based) caused by screening differed vastly; 25% in
      Denmark versus 10% in Norway. This study explores reasons for this difference.
      PATIENTS AND METHODS: We compared two published studies from the Danish and
      Norwegian screening programs (Olsen et al., 2005; Kalager et al., 2010)
      investigating biennial mammography screening for women age 50-69 years. Four
      comparison groups of women were constructed ('current' and 'historical screening
      groups'; 'current' and 'historical nonscreening groups') based on county of
      residence. We calculated incidence-based breast cancer mortality in the current
      versus the historical period for screening and nonscreening groups, using
      mortality rate ratios (MRR) in the two countries, accounting for concomitant
      changes in breast cancer mortality. RESULTS: In the screening groups, similar
      reductions in breast cancer mortality were found when periods preceding and
      following start of screening were compared, in Denmark [25%; MRR 0.75; 95%
      confidence interval (CI) 0.64% to 0.88%] and in Norway (28%; MRR 0.72; 95% CI
      0.63% to 0.81%). However, mortality increased in Denmark in the current
      nonscreening group compared with the historical nonscreening group; for women >59
      years, breast cancer mortality increased by 14% (MRR 1.14, 95% CI 1.07-1.22),
      whereas in Norway a 19% reduction was seen (MRR 0.81, 95% CI 0.72-0.92). This
      increase accounts for the different relative effect of screening in Denmark and
      Norway; 25% breast cancer mortality reduction in Denmark, 10% in Norway.
      CONCLUSIONS: The seemingly larger effect of screening in Denmark may not be
      solely attributable to screening itself, but to increased breast cancer mortality
      in women older than 59 years not invited to screening.

PMID- 24669013
TI  - Expression profiling stratifies mesothelioma tumors and signifies deregulation of
      spindle checkpoint pathway and microtubule network with therapeutic implications.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting
      resistance to most treatment regimens and requires effective therapeutic options.
      Though an effective strategy in many cancer, targeted therapy is relatively
      unexplored in MPM because the therapeutically important oncogenic pathways and
      networks in MPM are largely unknown. MATERIALS AND METHODS: We carried out gene
      expression microarray profiling of 53 surgically resected MPMs tumors along with
      paired normal tissue. We also carried out whole transcriptomic sequence (RNA-seq)
      analysis on eight tumor specimens. Taqman-based quantitative Reverse
      transcription polymerase chain reaction (qRT-PCR), western analysis and
      immunohistochemistry (IHC) analysis of mitotic arrest deficient-like 1 (MAD2L1)
      was carried out on tissue specimens. Cell viability assays of MPM cell lines were
      carried out to assess sensitivity to specific small molecule inhibitors. RESULTS:
      Bioinformatics analysis of the microarray data followed by pathway analysis
      revealed that the mitotic spindle assembly checkpoint (MSAC) pathway was most
      significantly altered in MPM tumors with upregulation of 18 component genes,
      including MAD2L1 gene. We validated the microarray data for MAD2L1 expression
      using quantitative qRT-PCR and western blot analysis on tissue lysates.
      Additionally, we analyzed expression of the MAD2L1 protein by IHC using an
      independent tissue microarray set of 80 MPM tissue samples. Robust clustering of
      gene expression data revealed three novel subgroups of tumors, with unique
      expression profiles, and showed differential expression of MSAC pathway genes.
      Network analysis of the microarray data showed the cytoskeleton/spindle
      microtubules network was the second-most significantly affected network. We also
      demonstrate that a nontaxane small molecule inhibitor, epothilone B, targeting
      the microtubules have great efficacy in decreasing viability of 14 MPM cell
      lines. CONCLUSIONS: Overall, our findings show that MPM tumors have significant
      deregulation of the MSAC pathway and the microtubule network, it can be
      classified into three novel molecular subgroups of potential therapeutic
      importance and epothilone B is a promising therapeutic agent for MPM.

PMID- 24669014
TI  - GDF15 is a potential predictive biomarker for TPF induction chemotherapy and
      promotes tumorigenesis and progression in oral squamous cell carcinoma.
AB  - BACKGROUND: Randomized trials have not shown major survival benefits when
      induction chemotherapy plus standard therapy is compared with standard therapy
      alone in patients with oral squamous cell carcinoma (OSCC). Induction
      chemotherapy is likely to be effective for biologically distinct subgroups and
      biomarker development may lead to identification of patients whose tumors are
      likely to respond to a particular treatment. PATIENTS AND METHODS: We evaluated
      immunohistochemical staining for GDF15 in pretreatment biopsy specimens of 230 of
      256 OSCC patients who were treated in a prospective, randomized, phase III trial
      on induction chemotherapy including docetaxel, cisplatin and 5-fluorouracil
      (TPF). Relationship between GDF15 intervention and cell proliferation, migration,
      invasion, colony formation and tumorigenicity was analyzed using in vitro and in
      vivo OSCC models. RESULTS: Low GDF15 expression predicted a better survival in
      OSCC patients, especially overall survival [P = 0.049, hazard ratio (HR) = 0.597]
      and distant metastasis-free survival (DMFS; P = 0.031, HR = 0.562). cN+ patients
      with low GDF15 expression benefitted from induction TPF in overall survival (P =
      0.039, HR = 0.247) and DMFS (P = 0.039, HR = 0.247), cN- patients with high GDF15
      expression benefitted from induction TPF in overall survival (P = 0.019, HR =
      0.231), disease-free survival (P = 0.011, HR = 0.281), locoregional recurrence
      free survival (P = 0.035, HR = 0.347) and DMFS (P = 0.009, HR = 0.197). Decreased
      GDF15 expression in OSCC lines significantly inhibited cell proliferation,
      migration, invasion, colony formation and tumorigenesis through increased
      phosphorylation of AKT and ERK1/2 (P < 0.05). Likewise, overexpression of GDF15
      significantly promoted cell proliferation, migration, invasion and colony
      formation through decreased phosphorylation of AKT and ERK1/2 (P < 0.05).
      CONCLUSIONS: GDF15 expression can be used as a prognostic biomarker for OSCC, and
      as a predictive biomarker for benefitting from TPF induction chemotherapy. GDF15
      promotes tumorigenesis and progression through phosphorylation of AKT and ERK1/2
      in OSCC. The clinical trial in this study was registered with
      www.ClinicalTrials.gov (NCT01542931).

PMID- 24669015
TI  - Open-label randomized clinical trial of standard neoadjuvant chemotherapy with
      paclitaxel followed by FEC versus the combination of paclitaxel and everolimus
      followed by FEC in women with triple receptor-negative breast cancer?.
AB  - BACKGROUND: Everolimus synergistically enhances taxane-induced cytotoxicity in
      breast cancer cells in vitro and in vivo in addition to demonstrating a direct
      antiproliferative activity. We aim to determine pharmacodynamics changes and
      response of adding everolimus to standard neoadjuvant chemotherapy in triple
      negative breast cancer (TNBC). PATIENTS AND METHODS: Phase II study in patients
      with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m(2) i.v. weekly for 12
      weeks, followed by 5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and
      cyclophosphamide 500 mg/m(2) every 3 weeks for four cycles) versus TR-FEC
      (paclitaxel 80 mg/m(2) i.v. and everolimus 30 mg PO weekly for 12 weeks, followed
      by FEC). Tumor samples were collected to assess molecular changes in the
      PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse
      phase protein arrays (RPPA). Clinical end points included 12-week clinical
      response rate (12-week RR), pathological complete response (pCR), and toxicity.
      RESULTS: Sixty-two patients were registered, and 50 were randomized, 27 received
      T-FEC, and 23 received TR-FEC. Median age was 48 (range 31-75). There was
      downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by
      ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4%
      (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did
      not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4
      toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both
      arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4
      stomatitis occurred. CONCLUSION: The addition of everolimus to paclitaxel was
      well tolerated. Everolimus downregulated mTOR signaling but downregulation of
      mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group. CLINICAL
      TRIAL NUMBER: NCT00499603.

PMID- 24669016
TI  - 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first
      line/second and further lines of treatment in advanced disease.
AB  - To complement the existing treatment guidelines for all tumour types, ESMO
      organises consensus conferences to focus on specific issues in each type of
      tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May
      2013 in Lugano. A total of 35 experts met to address several questions on non
      small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular
      biomarkers, first-line/second and further lines of treatment in advanced disease,
      early-stage disease and locally advanced disease. For each question,
      recommendations were made including reference to the grade of recommendation and
      level of evidence. This consensus paper focuses on first line/second and further
      lines of treatment in advanced disease. 

PMID- 24669017
TI  - Relevant risk of carboplatin underdosing in cancer patients with normal renal
      function using estimated GFR: lessons from a stage I seminoma cohort.
AB  - BACKGROUND: Seminoma stage I is the most frequent testis cancer and single-dose
      carboplatin (AUC7) is an effective and widely used adjuvant treatment.
      Underdosing of carboplatin by 10% has been shown to almost double the rate of
      relapse and hence correct dosing based on accurate GFR measurement is crucial.
      The gold standard of GFR measurement with a radiolabelled isotope is expensive
      and not readily available. In many institutions, it is replaced by GFR estimation
      with the Cockcroft-Gault formula, which might lead to significant carboplatin
      underdosing and potentially inferior clinical outcome. METHODS: Retrospective
      analysis of all patients with stage I seminoma treated with adjuvant carboplatin
      between 1999 and 2012. All patients had serum creatinine measured and underwent
      GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was
      compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI,
      Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy. Bias,
      precision, rates of under- and overdosing of GFR estimates were compared with
      measured GFR. Bland-Altman plots were done. RESULTS: A total of 426 consecutive
      Caucasian male patients were included: median age 39 years (range 19-60 years),
      median measured GFR 118 ml/min (51-209), median administered carboplatin dose
      1000 mg (532-1638). In comparison to isotopic GFR measurement, a relevant
      proportion of patients would have received <= 90% of carboplatin dose through the
      use of GFR estimation formulae: 4% using Mayo, 9% Martin, 18% Cockcroft-Gault,
      24% Wright, 63% Jelliffe, 49% MDRD and 41% using CKD-EPI. The flat dosing
      strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean
      percentage error of +1.9, +0.4 and +2.1, respectively. CONCLUSIONS: Using
      Cockcroft-Gault or any other formula for GFR estimation leads to underdosing of
      adjuvant carboplatin in a relevant number of patients with Seminoma stage I and
      should not be regarded as standard of care.

PMID- 24669018
TI  - Noncancer health events as a leading cause of competing mortality in advanced
      head and neck cancer.
AB  - BACKGROUND: The survival of patients with head and neck squamous cell carcinoma
      (HNSCC) can be affected by noncancer health events (NCHE) as well as by index
      cancer progression and second primary cancer (SPC). This study aimed to
      investigate the risk factors for NCHE and noncancer mortality (NCM) in patients
      with advanced-stage HNSCC. PATIENTS AND METHODS: This cohort study involved 600
      consecutive patients with overall stage III to IV HNSCC who were treated between
      2001 and 2010 at our tertiary referral hospital. NCHE was defined as re-admission
      (i.e. after the primary treatments for the index tumors) due to noncancer-related
      causes. The incidences of NCHE and NCM and their risk factors were analyzed by
      using cumulative incidence and cause-specific hazard functions. RESULTS: During a
      median follow-up period of 54 months, 224 (37.3%) and 55 (9.2%) of the 600
      patients had NCHE and NCM, respectively. The 5-year index cancer mortality, SPC
      mortality, and NCM rates were 23.8%, 4.2%, and 8.9%, respectively. Multivariate
      analyses revealed that body mass index <20 kg/m(2) (P = 0.018), Charlson
      comorbidity index (CCI) >=1 (P < 0.001), tumor recurrence (P < 0.001), SPC
      occurrence (P < 0.001), and initial chemotherapy (P = 0.049) were independent
      NCHE predictors. Older age (P < 0.001), CCI >=1 (P = 0.008), tumor recurrence (P
      < 0.001), and SPC occurrence (P = 0.047) were independent NCM predictors.
      Patients with respiratory NCHE were at a higher risk of NCM than patients with
      other NCHE types (P < 0.001). CONCLUSIONS: One or more comorbidities, tumor
      recurrence, and SPC occurrence were independent predictors of both NCHE and NCM.
      Patients with respiratory NCHE had a particularly high risk of NCM.

PMID- 24669019
TI  - Pregnancy related causes of deaths in Ghana.

PMID- 24669021
TI  - The immunological response of HIV-positive patients initiating HAART at the Komfo
      Anokye Teaching Hospital, Kumasi, Ghana.
AB  - OBJECTIVE: The study sought to document the experience of immunological
      improvement among Ghanaian PLHIV on HAART comparing different categories of
      patients. SETTING: Serology Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
      PARTICIPANTS: The study comprised a convenient sample of 303 treatment naive HIV
      patients due to start HAART. METHODS: Questionnaires were used to collect patient
      demographic and clinical data. Four CD4 counts were measured at six-monthly
      intervals to determine rates of CD4 change. These were pre-therapy, 1(st) post
      therapy, 2(nd) post-therapy, and 3(rd) post-therapy counts. The rates of CD4
      change among the different categories of patients were also compared. RESULTS: At
      baseline, women had higher CD4 count (mean of 77.4 cells/MUl), and mean age of
      participants was 40 years. The CD4 count increased from a mean baseline of 70.2
      cells/MUl to 229.2, 270.0, and 297.6 cells/MUl at 6, 12, and 18 months of
      treatment respectively (P < 0.0001 at each time point). There were no gender
      (P=0.46) and age (P=0.96) differences in treatment response. There was no
      difference (P=0.18) in treatment response comparing those with CD4 <250 cells/MUl
      and those whose CD4 count was between 250 and 350 cells/MUl at baseline although
      patients with baseline CD4 count <250 cells/MUl showed larger increases after 12
      months of treatment. Out of 282 patients with pre-therapy CD4 count <=250
      cells/MUl, 241 (85.5%) and 41 (14.5%) were adherents and nonadherents
      respectively. Mean rate of increase was 15.2 and 8.4 cells/MUl/month in adherent
      and non-adherent patients respectively (p=0.2). CONCLUSION: The study suggests
      that a sustained CD4 increase could be achieved in adherent patients commencing
      therapy with baseline CD4 count <=250 cells/MUl, and that these patients have
      greater ability for immunological recovery during 12 months of treatment The
      study, therefore, concludes that significant immunological improvement is
      possible among Ghanaian PLHIV on HAART as long as a high level of treatment
      adherence is observed.

PMID- 24669020
TI  - Pregnancy related causes of deaths in Ghana: a 5-year retrospective study.
AB  - OBJECTIVE: Data on maternal mortality varies by region and data source. Accurate
      local-level data are essential to appreciate its burden. This study uses autopsy
      results to assess maternal mortality causes in southern Ghana. METHODS: Autopsy
      log books of the Department of Pathology, Korle-Bu Teaching Hospital Mortuary
      were reviewed from 2004 through 2008 for pregnancy related deaths. Data were
      entered into a database and analyzed using SPSS statistical software (Version
      19). RESULTS: Of 5,247 deaths among women aged 15-49, 12.1% (634) were pregnancy
      related. Eighty one percent of pregnancy-related deaths (517) occurred in the
      community or within 24 hours of admission to a health facility and 18.5% (117)
      occurred in a health facility. Out of 634 pregnancy-related deaths, 79.5% (504)
      resulted from direct obstetric causes, including: haemorrhage (21.8%), abortion
      (20.8%), hypertensive disorders (19.4%), ectopic gestation (8.7%), uterine
      rupture (4.3%) and genital tract sepsis (2.5%). The remaining 20.5% (130)
      resulted from indirect obstetric causes, including: infections outside the
      genital tract, (9.2%), anemia (2.8%), sickle cell disease (2.7%), pulmonary
      embolism (1.9%) and disseminated intravascular coagulation (1.3%). The top five
      causes of maternal death were: haemorrhage (21.8%), abortion (20.7%),
      hypertensive disorders (19.4%), infections (9.1%) and ectopic gestation (8.7%).
      CONCLUSION: Ghana continues to have persistently high levels of preventable
      causes of maternal deaths. Community based studies, on maternal mortality are
      urgently needed in Ghana, since our autopsy studies indicates that 81% of deaths
      recorded in this study occurred in the community or within 24 hours of admission
      to a health facility.

PMID- 24669022
TI  - Adrenocortical function in Nigerians with human immunodeficiency virus infection.
AB  - OBJECTIVE: This study sets out to determine the prevalence of adrenocortical
      insufficiency in persons with HIV infection by determining the response to low
      dose (1 ug) ACTH stimulation. DESIGN: An experimental study involving people with
      HIV infection and healthy people. SETTING: The study group and the controls were
      recruited from the Lagos University Teaching Hospital (LUTH). PARTICIPANTS: forty
      three newly diagnosed and treatment naive persons with HIV (23 males and 20
      females) and 70 (35 males and 35 females) HIV negative subjects completed the
      study. INTERVENTION: One ug Synacthen was given intravenously to stimulate the
      adrenal glands. MAIN OUTCOME MEASURES: Blood was collected for basal cortisol
      levels and 30 minutes after the injection of ACTH. Cortisol was assayed using
      ELISA. RESULTS: The mean basal cortisol was 154.9 +/- 27.2 nmol/L and 239.9 +/-
      31.6 nmol/L (p<0.001); while the 30-minute post ACTH test cortisol level was
      354.8 +/- 19.9 nmol/L and 870.9 +/- 163.5 nmol/L (p<0.001) and the increment was
      100.0 +/- 17.2 nmol/L and 588.8 +/- 143.4 nmol/L (p<0.001) in HIV and healthy
      subject group respectively. Using the diagnostic criteria derived for the
      diagnosis of adrenocortical insufficiency in this study (30 minute cortisol level
      <380.2 nmol/L and increment from basal to stimulated cortisol level <158.5
      nmol/L); fifteen (34.8%) persons with HIV had adrenal insufficiency. CONCLUSION:
      Adrenocortical insufficiency is common in persons with HIV infection, occurring
      in about 34.8% of patients studied. Clinically evident adrenocortical
      insufficiency is uncommon in persons with HIV.

PMID- 24669023
TI  - Perceptions of medical students about family medicine in Ghana.
AB  - OBJECTIVES: To determine the perceptions of medical students in Ghana about
      family medicine with regard to knowledge and relevance as well as specialty
      preferences. DESIGN: A descriptive study. METHOD: The study was conducted on
      first clinical year students of the University of Ghana Medical School (first
      group of students introduced to the specialty of family medicine) in July 2008,
      using structured questionnaire. Data was analyzed by descriptive statistics. MAIN
      OUTCOME MEASURES: The respondents' awareness of family medicine, their views on
      the relevance of family medicine and their specialty preferences. RESULTS: Level
      of awareness of the specialty was high among the students (88.0%, [95% CI 80.2
      93.6]). Information from friends and relations was the major source of awareness
      (29.5%, CI 20.2-40.3). Majority of the students perceived that family physicians
      are capable of providing total health care for 85-95% of their clients (54.4%, CI
      44.1-64.5) and also reduce overall cost of health care (79.8%, CI 70.5-87.2).
      However, only 2.4% (CI 0.4-7.6) were considering postgraduate training in family
      medicine. The major factor for specialty choice was personal interest (75.6%, CI
      65.9-83.6) and the main reason for not choosing family medicine was inadequate
      understanding of the specialty (79.3%, CI 69.5-87.0). CONCLUSION: There is high
      level of awareness of family medicine among medical students in Ghana however
      very few students want to choose it as a specialty because of inadequate
      understanding of the specialty.

PMID- 24669024
TI  - Indications and complications of major limb amputations in Kano, Nigeria.
AB  - OBJECTIVES: To determine the indications and complications of major limb
      amputations in a Nigerian hospital. DESIGN: A five-year retrospective descriptive
      study. SETTING: National Orthopaedic Hospital, Dala, Kano, Nigeria. PARTICIPANTS:
      Patients who had amputations above the wrist or ankle between January 2006 and
      December 2010. MAIN OUTCOME MEASURES: Indications, complications and mortality.
      RESULTS: There were 132 unilateral amputations. The patients were mostly males
      and below the age of 40. Lower limb amputations (74.2%) exceeded upper limb
      amputations (25.8%). The commonest indication was trauma (42.4%) followed by TBS
      gangrene (31.8%) and malignant tumours (12.9%). Wound infection, the commonest
      complication, occurred in patients who had identifiable predisposing factors. The
      3 deaths that occurred were in patients who had had traditional bone setter
      intervention: 2 were due to septicaemia; 1, due to severe tetanus. CONCLUSION:
      Trauma and traditional bone setter gangrene were the commonest indications. Most
      of the amputations were avoidable. Institution of preventive measures is
      imperative. Paying attention to predisposing factors can reduce complications.

PMID- 24669025
TI  - The relationship between metabolic syndrome and target organ damage in Ghanaian
      with stage-2 hypertension.
AB  - OBJECTIVES: To determine the frequency of Metabolic syndrome (MetS) in stage-2
      hypertension and to assess the influence of MetS components over target organ
      damage (TOD) in Ghanaian patients. METHODS: Forty adult patients with stage-2
      hypertension were enrolled in a cross-sectional study developed at the Police
      Hospital, Accra, between 1st February 2009 and 31st January 2010. Diagnosis of
      MetS was based on The National Cholesterol Education Program in Adult Treatment
      Panel Revised in 2005 criteria. The alterations on the heart, aortic and carotid
      arteries, retina, and kidneys were evaluated through the clinical examination
      including retinal funduscopy, chest X-Ray, ECG, and serum creatinine
      quantification. The Brain CT-scan was performed on the patients with clinical
      cerebrovascular disease manifestations. RESULTS: MetS was diagnosed in 25 cases
      (62.5%); female sex revealed significant association with MetS (OR, 4.88; 95% CI,
      1.19-19.94; P=0.027). Ninety-five percent of patients had TOD. Coronary disease
      was associated with MetS (OR, 4.43; 95% CI, 1.026-19,27; P=0.047) and diabetes
      mellitus as single MetS component (OR, 14.00; 95% CI, 1.56-125.61; P=0.018). A
      positive significant correlation was shown of age with cerebrovascular disease
      (r=0.381; P=0.015) and coronary disease (r=0.623; P=0.000). Non-significant
      correlation or association (P>0.05) was shown between number of MetS components
      and number of TOD. CONCLUSIONS: In stage-2 hypertension patients a high frequency
      of MetS with a risk increase in female sex was observed. This stage hypertension
      is for itself an individual risk to develop cardiovascular disease with high
      frequency none related with MetS, although coronary disease risk was increased in
      diabetic patients.

PMID- 24669026
TI  - An exploratory study of physical activity and over-weight in two senior high
      schools in the Accra Metropolis.
AB  - BACKGROUND: Overweight and physical inactivity are major risk factors for non
      communicable diseases. However, little evidence on physical activity, and
      overweight exists to support intervention in specific sub-populations including
      adolescents in low-income settings like Ghana. This study aimed at estimating
      overweight and determining the pattern and level of physical activity among
      senior high school students in the Accra Metropolis. METHODS: A cross-sectional
      study was conducted in the Accra Metropolis, among senior high school students,
      ages 15 to 19 years. Participants were selected using a two-stage cluster
      sampling technique. Structured questionnaire and anthropometric measurement were
      employed to gather information for the study. Students were considered as
      overweight if their Body Mass Index (BMI) >= +1SD, and obese if BMI >= +2SD.
      RESULTS: Out of 444 students, 17% were classified as engaging in low level
      physical activity, 49% in moderate activity, and 34% in high level of physical
      activity. Much of the activity in boys was recreational while among girls, was
      due to domestic chores. The prevalence of overweight was 11.7%. Overweight
      prevalence was higher among female students (15.6%) compared to 4.5% in males.
      Furthermore the risk of overweight was lower among students who engaged in high
      physical activity than those engaged in low activity. Overweight was
      independently associated with physical activity (p=0.01), sex (p=0.001) and age
      (p=0.01), after controlling for age sex and physical activity and diet.
      CONCLUSION: Majority of students in the study engaged in moderate to high
      physical activity. The prevalence of overweight was 11.7%. Physical activity was
      significantly related to overweight among students in the study.

PMID- 24669027
TI  - Spontaneous extra-hepatic bile duct perforation postpartum.
AB  - Spontaneous bile duct perforation is an unusual cause of acute abdomen. It is an
      extremely rare condition and rarely suspected or correctly diagnosed pre
      operatively. A case of a 29 year old adult female, presenting with peritonitis, 2
      days post partum is presented. Exploratory laparotomy showed biliary peritonitis
      secondary to a perforated common bile duct. She had a cholecystectomy and closure
      of the perforation over a T-tube. She recovered well and was discharged home.
      Awareness of spontaneous common bile duct perforation as a rare cause of biliary
      peritonitis, avoids undue delay in the diagnosis and thus improve prognosis.
      Cholecystectomy and drainage of bile duct using a T-tube is emphasized.

PMID- 24669029
TI  - Employment of colour flow Doppler to identify the tip of the needle during
      ultrasound guided nerve blocks.

PMID- 24669028
TI  - An unusually large spindle cell sarcoma of the tongue in a male child.
AB  - Reports of spindle cell sarcoma in the tongue are very rare, and seldom in the
      child. We report a five-year-old male patient who presented with a massive lesion
      on the right side of the tongue. This was surgically excised and histologically
      diagnosed as a Spindle cell Sarcoma. Results of bone marrow aspiration further
      revealed that about 16% of his bone marrow was infiltrated with abnormal
      pleomorphic vacuolated cells with bluish cytoplasm, consistent with
      rhabdomyosarcoma (RMS) cells. The child was treated with surgery and chemotherapy
      with good initial response, but then died after one year following a relapse.

PMID- 24669030
TI  - Expression of the matrix metalloproteases 2, 14, 24, and 25 and tissue inhibitor
      3 as potential molecular markers in advanced human gastric cancer.
AB  - BACKGROUND: During progression of gastric cancer (GC), degradation of the
      extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their
      tissue inhibitors (TIMPs): changes in the expression of these have been related
      to unfavorable prognosis in GC. OBJECTIVE: To analyze the expression of certain
      MMPs and TIMPs in chronic superficial gastritis (SG) and GC. METHODS: The
      expression of MMPs and TIMPs was determined using qRT-PCR; the expression was
      classified, using threshold cycle (C(T)) values, as very high (C(T) <= 25), high
      (C(T) = 26-30), moderate (C(T) = 31-35), low (C(T) = 36-39), or not detected
      (C(T) = 40). Strength of association was estimated between the proteins, which
      were detected by Western blot, and the risk of developing GC. RESULTS: We found a
      high expression of MMP1, MMP2, MMP14, TIMP1, and TIMP3; moderate one of MMP9 and
      MMP25, and low one of MMP13 and MMP24 in both tissues. In absolute mRNA levels,
      significant differences were found in expression of MMP2, MMP24, and MMP25, which
      are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and
      TIMP-3 was associated with the risk of developing GC. CONCLUSIONS: We consider
      that MMP2, MMP24, and MMP25 and the proteins MMP-14 and TIMP-3 could be
      candidates for prognostic molecular markers in GC.

PMID- 24669032
TI  - A study of the effect of nasal modes of ventilation on the incidence of gastro
      oesophageal reflux in preterm neonates.
AB  - BACKGROUND: Nasal modes of respiratory support cause variable amounts of gastric
      dilatation which may increase gastro-oesophageal reflux (GER) in preterms. To
      compare the incidence of GER in nasally ventilated, preterm babies with controls
      (babies not on ventilation). TYPE OF STUDY: A prospective, observational
      comparative study. METHOD: Twenty-three preterm babies of gestational age 28-36
      weeks and weight ranging between 1,000 g and < 2,500 g on either nasal continuous
      positive airway pressure (nCPAP) or nasal intermittent positive pressure venti
      lation (nIPPV) were assessed for GER. They were compared with controls not on
      ventilation some of who were test babies when off ventilation (subgroup A) and
      some were unrelated babies not on ventilator but matched for gestational age and
      weight with test babies (subgroup B). All babies were subjected to continuous,
      oesophageal pH monitoring with dual sensor (upper and lower oesophageal)
      catheters. Reflux index (RI) was calculated as the percentage of study time the
      lower oesophageal pH was < 4. Primary outcome was the RI in the test and controls
      groups. Secondary outcome was the temporal relation of the reflux with symptoms
      if any. Numerical data were shown as mean with standard deviation and statistical
      comparisons were done using the chi(2)-test, Fischer test, and t-test wherever
      applicable. RESULTS: The RI was higher in ventilated babies as compared to the
      control group, particularly in the subgroup A, where test babies formed their own
      controls. Grade IV reflux (7 cases) was seen only in the ventilated babies. There
      was no difference in the incidence of GER in babies on nCPAP as compared with
      nIPPV. Grade IV reflux could not be reliably predicted by RI alone. No definite
      temporal relation between episodes of reflux and symptoms could be determined in
      this study. CONCLUSION: There is an increase in GER in preterms on nasal modes of
      ventilation. A combination of upper (pharyngeal) and lower oesophageal sensors
      are preferred to a single lower oesophageal sensor when assessing GER by
      oesophageal pHmetry in neonates.

PMID- 24669031
TI  - Identification of human tissue kallikrein 6 as a potential marker of laryngeal
      cancer based on the relevant secretory/releasing protein database.
AB  - OBJECTIVE: This study was aimed to create a large-scale laryngeal cancer relevant
      secretory/releasing protein database and further discover candidate biomarkers.
      METHODS: Primary tissue cultures were established using tumor tissues and matched
      normal mucosal tissues collected from four laryngeal cancer patients. Serum-free
      conditioned medium (CM) samples were collected. These samples were then
      sequentially processed by SDS-PAGE separation, trypsin digestion, and LC-MS/MS
      analysis. The candidates in the database were validated by ELISA using plasma
      samples from laryngeal cancer patients, benign patients, and healthy individuals.
      RESULTS: Combining MS data from the tumor tissues and normal tissues, 982
      proteins were identified in total; extracellular proteins and cell surface
      proteins accounted for 15.0% and 4.3%, respectively. According to stringent
      criteria, 49 proteins were selected as candidates worthy of further validation.
      Of these, human tissue kallikrein 6 (KLK6) was verified. The level of KLK6 was
      significantly increased in the plasma samples from the cancer cohort compared to
      the benign and healthy cohorts and moreover showed a slight decrease in the
      postoperative plasma samples in comparison to the preoperative plasma samples.
      CONCLUSIONS: This laryngeal cancer-derived protein database provides a promising
      repository of candidate blood biomarkers for laryngeal cancer. The diagnostic
      potential of KLK6 deserves further investigation.

PMID- 24669033
TI  - Prevalence of occult hepatitis B amongst Indian human immunodeficiency virus type
      1 infected individuals-a pilot study.
AB  - BACKGROUND: The diagnosis of hepatitis B is routinely based on the detection of
      hepatitis B surface antigen (HBsAg) only. However, occult hepatitis B virus (HBV)
      infection (OBI), which is defined as infection with positive hepatitis B core
      antibody (anti-HBc) antibodies, positive DNA (deoxyribonucleic acid) PCR
      (polymerase chain reaction), and undetectable HBsAg, as well as anti-HBs
      antibodies in serum or plasma of HBV infected individuals, will remain undetected
      using this screening diagnostic approach of detecting HBsAg. The current study
      aims in studying the prevalence of the OBI amongst human immunodeficiency virus
      type 1 (HIV-1) infected individuals who have not been exposed to anti-retroviral
      therapy. METHOD: Estimation of HBsAg, anti-HBs, and anti-HBc total antibody
      status amongst 100 HIV-1 infected study participants was carried out using enzyme
      linked immunosorbent assay (ELISA) kits. Detection of HBV-DNA was carried out by
      in-house qualitative PCR. CD4 + T lymphocyte counts were analysed using Becton
      Dickinson's (BD) FACSCountTM system. RESULTS: The median age of the HIV-1
      infected study population was 35 years (range: 22-67), with the gender
      distribution being 53 males and 47 females. The mean CD4 T lymphocyte count of
      the study participants was 210/mm(3). Overall, serological evidence of HBV
      infection was observed in 28% of the HIV-1 infected study participants. There was
      5% seropositivity for HBsAg, of which 2% were additionally positive for HBV-DNA
      PCR. "Anti-HBc alone" status was seen in 18% of study participants, this being
      statistically higher in those with CD4 T lymphocyte counts < 200/mm(3). While
      there was a single specimen with co-positivity for anti-HBc total antibodies and
      HBV-DNA, 5% of the in the study population exhibited anti-HBs antibodies
      positivity, with one sample exhibiting dual positivity for HBsAg and anti-HBs
      antibodies. CONCLUSION: Occult HBV infections may contribute to chronic liver
      damage, and associ-ated reactivation amongst immunocompromised individuals, HIV-1
      in-fected being a subset of them. "Anti-HBc" testing followed by HBV-DNA
      detection by PCR can be utilised for such populations to detect OBIs. Early
      detection of hepatitis B viraemia will be important for deciding the antiviral
      therapeutic protocol so as to avoid evolution of antiviral resistance in the
      circulating HBV strains in HIV-1 infected individuals harbouring OBIs.

PMID- 24669034
TI  - Cutaneous manifestations of HIV-a detailed study of morphological variants,
      markers of advanced disease, and the changing spectrum.
AB  - BACKGROUND: Cutaneous manifestations are early and easily identifiable markers of
      human immunodeficiency virus (HIV) infection. They can help in predicting
      severity and progress of the disease and can be correlated well with CD4 counts.
      This study was undertaken to study the cutaneous manifestations of HIV infection
      and to correlate them with CD4 counts. It also aimed to study the changing
      spectrum of these manifestations and describe cutaneous manifestations seen in
      advanced disease. METHOD: A total of 234 HIV-positive patients not on anti
      retroviral therapy, who attended the outpatient department or were admitted as
      inpatients at Military Hospital, Shillong during the period between May 2008 and
      October 2009 were included. Cutaneous, mucosal, and genitourinary manifestations
      in these patients were studied in detail and were correlated with CD4 counts.
      RESULTS: Infections were the most common group of mucocutaneous manifestations,
      while onychomycosis was the commonly observed individual manifestation. A
      different set of cutaneous markers for advanced HIV disease was observed and new
      parameters for therapy were also arrived at. CONCLUSION: Specific morphological
      variants of cutaneous markers may provide a better clue to early diagnosis of HIV
      and can help in diagnosing advanced stages of the disease. Fresh cutaneous
      markers are required for indicating cut-off levels of CD4 count at 350/MUL for
      starting therapy.

PMID- 24669035
TI  - Changing trends of transfusion transmitted viral infections among blood donors in
      the last decade-a 10-year study in a large tertiary care blood bank (2000-2009.
AB  - BACKGROUND: The main blood borne viruses' viz. hepatitis B virus (HBV), human
      immunodeficiency virus (HIV), and hepatitis C virus (HCV), are a major public
      health issue, and represent significant causes of morbidity and mortality
      associated with transfusion. This study analysed the trends of blood borne
      infections among blood donors in a large blood bank in the last 10 years. METHOD:
      Viral screening results of 80,500 voluntary and replacement donations from 2000
      to 2009 were analysed. All donations were screened for HBV, HCV, and HIV. The
      seroprevalence rate of HBV, HCV, and HIV infections and 95% confidence interval
      were calculated. RESULTS: The seroprevalence rate of HBV, HIV, and HCV, decreased
      during the last 10-years study from 2000 to 2009. There is significant and
      impressive decrease in HBV seroprevalence rate from 2.39% in 2000 to 1.28% in
      2009. The seroprevalence rate of HIV appeared to have decreased with a very
      significant value from 1.32% to 0.30% in 2009. Hepatitis C virus seroprevalence
      rate showed a slight decline in blood donations from 0.48% in 2001 to 0.22% in
      2009. CONCLUSION: There is a general reduction in the seroprevalence rate of
      viral infections. This is probably because of discouragement of professional or
      paid donations; better awareness, better prophylactic measures, and availability
      of vaccines have played a major role.

PMID- 24669036
TI  - Hypertension and catecholamine levels in sleep apnoea.
AB  - BACKGROUND: Sleep-disordered breathing has been strongly associated with systemic
      hypertension. Increased sympathetic activity in sleep-disordered breathing may be
      responsible for this association. METHOD: In this sleep clinic-based study, 82
      newly diagnosed patients of sleep-disordered breathing were evaluated for
      hypertension, and their plasma and urinary levels of catecholamines were
      measured. Catecholamine levels were then compared separately with the severity of
      sleep apnoea and blood pressure (BP). RESULTS: The prevalence of hypertension in
      the study population was 46.3%. The BP showed a strong and statistically
      significant correlation with apnoea-hypopnoea index (diastolic, r = 0.65, P <
      0.001 and systolic, r = 0.60, P < 0.001) which was maintained even after the
      results were analysed separately for obese and non-obese subjects. Both plasma
      and urinary levels of catecholamines were greater in patients with severe sleep
      apnoea (compared to nonsevere cases) and in those with hypertension compared to
      normotensives. However, statistical significance was achieved only for urine
      catecholamines and not for plasma catechol-amines in both the cases. CONCLUSION:
      Hypertension is highly prevalent among Indian subjects with obstructive sleep
      apnoea. Catecholamine levels are significantly higher in hypertensive than in
      normotensive apnoeics and are also directly related to the severity of
      obstructive sleep apnoea. Twenty-four hour urinary catecholamine levels are more
      valid measures of sympathetic activity than spot plasma samples.

PMID- 24669037
TI  - Journal scan.

PMID- 24669038
TI  - Comparative evaluation of bioglass with calcium sulphate beta-hemihydrate for the
      treatment of intraosseous defects-a clinico-radiological study.
AB  - BACKGROUND: The aim of the present clinical and radiological study was to compare
      bioglass and calcium sulphate beta-hemihydrate in the treatment of intraosseous
      defect in chronic periodontitis. METHOD: A total of 50 subjects with bilaterally
      symmetrical periodontal osseous defects with probing pocket depth = 5 mm and
      intraosseous defects >= 3 mm as seen on the radiographs were undertaken for the
      study. In one site (group A) bioactive glass was placed in defect and in
      contralateral site (group B) calcium sulphate beta-hemihydrate was used in the
      defect site. RESULTS: Clinical improvement was noted in all patients at the end
      of study. Both the groups showed reduction in probing pocket depth, increase in
      clinical attachment level, and reduction in osseous defect. Both materials were
      effective in achieving osseous gain. CONCLUSION: The osseous gain in group A
      subjects was 58.93%, whereas in group B subjects it was 48.56%. Calcium sulphate
      beta-hemihydrates showed promising results and were cost effective.

PMID- 24669039
TI  - Pulmonary metastases: a rare cause for pulmonary artery invasion and in situ
      pulmonary artery thrombosis-demonstration with multidetector computed tomography.

PMID- 24669040
TI  - Hypoglycaemia presenting as sole manifestation of hepatocellular carcinoma.

PMID- 24669041
TI  - Congenital high airway obstruction syndrome-antenatal diagnosis of a rare case of
      airway obstruction using multimodality imaging.

PMID- 24669042
TI  - Cerebral arteriopathy in neurofibromatosis type 1.

PMID- 24669043
TI  - Successful laparoscopic management of four cases of cholecystoduodenal fistula.

PMID- 24669044
TI  - Stress in the Indian Armed Forces: how true and what to do?

PMID- 24669045
TI  - Training-associated injuries among Armed Forces trainees.

PMID- 24669046
TI  - Liver transplantation in Armed Forces-new kid on the block.

PMID- 24669047
TI  - Liver transplantation in Indian Armed Forces-initial experience.
AB  - BACKGROUND: This study retrospectively analyses the initial experience of liver
      transplantation (LT) in the Indian Armed Forces. METHODS: Fifty-three patients
      underwent LT at Army Hospital (R&R) Delhi Cantt. between March 2007 and March
      2011. Of these 35 patients underwent deceased donor liver transplantation (DDLT)
      and living donor liver transplantation (LDLT) was carried out in 18 patients. The
      surgical techniques, complications and mortality were analysed. RESULTS: A high
      consent rate of 35.9% for organ donation was achieved by the Armed Forces Organ
      Retrieval and Transplantation Authority (AORTA). Biliary complications occurred
      in five patients (9.4%). However, most of them could be managed by endoscopic
      interventions. Hepatic artery thrombosis (HAT) occurred in five patients (9.4%).
      Of these, two DDLT grafts were revascularised following HAT, by creating extra
      anatomic arterial conduits with excellent outcome. The overall mortality was
      18.8% (n = 10). There was no significant difference in the overall complications
      or mortality in patients undergoing DDLT or LDLT. CONCLUSION: The overall
      survival and morbidity in this study is comparable to those from other centres.
      Urgent revascularisation of grafts following HAT should be attempted as it can
      salvage grafts with satisfactory outcome. There is a reduction in the incidence
      of biliary complications with refinements in surgical techniques.

PMID- 24669048
TI  - Stress fractures-a prospective study amongst recruits.
AB  - BACKGROUND: Stress fracture (SF) is the single most common cause for the lost
      number of manpower days during training of recruits in the Armed Forces. This
      prospective study was undertaken with a view to develop baseline data on
      incidence of SF and to identify related variables. METHODS: A prospective study
      over a period of five years during 2004-2009 in which a total of 8,570 recruits
      were enrolled at the start of their training to find out the incidence and
      pattern of SFs. RESULTS: A total of 604 (7.04%, 95% CI 6.40-7.40%) out of a total
      of 8,570 recruits sustained SF during the study period. The majority of fractures
      occurred during basic training. The factors like urban residence, vegetarianism
      and those without prior history of physical activity were found to be associated
      with SF. Tibia was the commonest bone involved. CONCLUSION: Prevention is
      undoubtedly the best approach in SF and other sports injuries. Priority should be
      given to individuals with good sports and physical activity background during
      recruitment. Intensity of training should be gradually increased during first
      three months (12 weeks) of training.

PMID- 24669049
TI  - Journal scan.

PMID- 24669050
TI  - High prevalence of hepatitis C virus-ribonucleic acid positivity in anti
      hepatitis C virus negative renal transplant patients.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is common in renal transplant (RT)
      patients. Some of these patients remain anti-HCV negative despite presence of
      infection and these are identified by a positive HCV-ribonucleic acid (RNA) test.
      METHODS: We studied 404 RT patients for prevalence of HCV-RNA positivity in anti
      HCV negative patients. Serum was tested for presence of anti-HCV antibodies using
      a third generation HCV micro-ELISA (enzyme-linked immunosorbent assay) test,
      which utilises a combination of HCV structural and nonstructural antigens. The
      RNA was extracted from patient serum for HCV viral quantification using Quiagen
      Ql Amp Viral RNA mini extraction kit. The HCV-RNA viral load was performed on
      Corbet Rotor Gene 3000 thermocycler using Taqman principle. RESULTS: About 308
      patients were anti-HCV negative and 96 were anti-HCV positive, resulting in
      prevalence of overt HCV infection of 23.7%. A total of 130 anti-HCV negative
      patients tested positive for HCV-RNA making a prevalence of occult HCV infection
      of 42.2%. There was no significant difference in the rate of overt or occult HCV
      infection between males and females. Patients with HCV infection (whether overt
      or occult) had received more number of dialysis sessions (62.5 vs 32.2) and blood
      transfusions (2.78 vs 1.99) when compared to those without HCV infection
      (P=0.001). The mean duration on dialysis was also longer (8.15 months vs 4.53
      months) in patients with HCV infection (P= 0.0001). CONCLUSION: A direct test for
      HCV viraemia is important to accurately determine the epidemiology of HCV
      infection in RT patients who remain anti-HCV negative despite harbouring active
      HCV infection.

PMID- 24669051
TI  - Intracervical versus vaginal misoprostol for cervical dilatation prior to
      operative hysteroscopy-a comparative study.
AB  - BACKGROUND: Hysteroscopic surgery requires pre-operative cervical ripening to
      facilitate adequate dilatation of the cervix for insertion of operative
      hysteroscope. This study was conducted to compare the efficacy of intracervical
      misoprostol with vaginal misoprostol in achieving cervical ripening before
      operative hysteroscopy. METHODS: In this randomised comparative study conducted
      at a tertiary care teaching hospital, 56 patients needing operative hysteroscopy
      were divided into two groups of 28 patients, one for intracervical misoprostol
      and the other for vaginal misoprostol. Four hundred microgram of misoprostol was
      inserted on the night before and in the morning of operative hysteroscopy
      intracervically in group I and vaginally in group II. RESULTS: Primary outcome
      measure was number of patients achieving 7 mm preoperative dilatation of cervix.
      Largest Hegar dilator that could be passed into the uterine cavity past the
      internal optic sheath without resistance was noted in each case. Mean cervical
      dilatation prior to operative hysteroscopy was calculated. In addition, incidence
      of slipping of vulsellum and cervical laceration was also noted. Time to achieve
      full cervical dilatation was recorded. In 23/28 cases of group I and 5/28 in
      group II, size 7 Hegar dilator could be passed without effort. Mean cervical
      dilatation was 7.5 mm in group I and 5.7 mm in group II. Slipping of the
      vulsellum and cervical lacerations were seen in significantly less patients in
      group I. Mean time to achieve cervical dilatation to 10 mm was 43.39 seconds in
      group I and 103.96 seconds in group II (P<0.0001). CONCLUSION: Intracervical
      administration of misoprostol is an effective method of achieving cervical
      ripening for easy cervical dilatation up to 10 mm prior to operative
      hysteroscopy.

PMID- 24669052
TI  - Perinatal outcomes among children born by assisted reproductive techniques-a
      hospital-based case control study.
AB  - BACKGROUND: Widespread use of assisted reproductive techniques (ART) has raised
      major concern about the outcome of resulting pregnancies, as well as about the
      health of the newborn children. The ART conceived pregnancies have an increased
      risk for prematurity and low birth weight (LBW). The risk of congenital
      malformations among children conceived via ART is contemplated to be high. The
      present case control study was conducted with an aim of analysing perinatal
      outcomes of children born by ART in the Indian context. METHODS: The case control
      study was conducted in the Army Hospital (Research and Referral), New Delhi. It
      included 82 cases and 164 controls. The data was collected on maternal and
      newborn characteristics among cases and controls. Perinatal outcomes were
      compared between ART conceived and spontaneously pregnant women in terms of birth
      weight, preterm, multiple pregnancies, and neonatal complications. RESULTS:
      Significant difference was observed in terms of the preterm delivery, birth
      weight, neonatal complications between the cases and the controls. The adjusted
      odds ratio (OR) was 21.6 (95% confidence interval [CI] 4.3, 112.9) for preterm
      delivery; 6.0 (95% CI 1.1, 43.8) for multiple pregnancy and 3.2 (95% CI 1.5, 7.0)
      for caesarean section. The risk of LBW and neonatal complications was heavily
      confounded by preterm delivery and multiple pregnancies, the adjusted OR being
      0.9 and 1.0, respectively. CONCLUSION: Increased risk of preterm delivery,
      multiple pregnancies and caesarean section was associated with ART. The LBW was
      confounded by preterm delivery and multiple pregnancies.

PMID- 24669053
TI  - Measuring domestic violence in human immunodeficiency virus-positive women.
AB  - BACKGROUND: Violence affects the lives of millions of women worldwide, in all
      socioeconomic classes. Violence and the fear of violence are emerging as
      important risk factor contributing to the vulnerability to human immunodeficiency
      virus (HIV) infection for women. The objective of the present cross sectional
      study is to compare the experiences of domestic violence between HIV-positive and
      HIV-negative married women seeking treatment in a tertiary care hospital.
      METHODS: The study is conducted in a tertiary care hospital in Pune on a randomly
      selected 150 married women (75 HIV-positive and 75 HIV-negative). Informed
      consent was obtained from all the women and also a trained counsellor was present
      during the process of data collection. The data was collected by interview method
      by taking precautions as laid down in the World Health Organization's ethical and
      safety recommendations for research on domestic violence and using modified
      conflict tactics scale (CTS). The definition of violence followed is as per the
      Declaration on the Elimination of Violence against Women, adopted by the United
      Nations General Assembly in 1993. RESULTS: The percentage of women reporting
      domestic violence is 44.7% (95% confidence interval [CI] = 36.84-52.68). The
      proportion of physical, emotional and sexual violence reported is 38% (95% CI =
      30.49-45.96), 24% (95% CI = 17.67-31.31), and 14.7% (95% CI = 9.66-21.02),
      respectively. The odds of reporting violence of all forms is significantly higher
      among HIV-positive women than among HIV-negative women (P<0.05). Univariate and
      multivariate logistic regression is carried out to examine the possible
      predictors of domestic violence. CONCLUSION: The findings suggest high proportion
      of HIV-positive women report violence then HIV-negative women which must be
      addressed through multilevel prevention approaches.

PMID- 24669054
TI  - Journal scan.

PMID- 24669055
TI  - Effect of firing cycle and surface finishing on the sag resistance of long-span
      metal ceramic framework using base metal alloys-an in vitro study.
AB  - BACKGROUND: The search for the ideal restorative material or combination of
      materials in dentistry is still the subject of modern dental research. In
      clinical practice, there are increased numbers of ceramo-metal restorations being
      fabricated which replace multiple missing teeth in a single framework. The
      literature is scanty with regard to investigations of the 'sag' resistance of
      base metal alloys commonly used for ceramo-metal restorations and specifically
      for long-span restorations. An in vitro study was carried out to investigate the
      effects of surface finishing and simulated porcelain-firing on the sag resistance
      of long-span ceramo-metal frameworks using base metal alloys. METHOD: Four types
      of alloys were used. A total of 80 samples were selected for the study and they
      were divided into four groups of 20 samples each. 'As cast' metal specimens in
      group I, group II and with surface finishing in group III and group IV. Each test
      sample was mounted on the sample holding accessory of the custom made thermo
      mechanical analyser and subjected to three firing cycles. Each sample was
      evaluated for the sag-related deflection recorded by the dial gauge with an
      accuracy of 1 um. The data recorded was subjected to a statistical analysis using
      unpaired t-test to compare the relative difference in the sag-related deflection
      values. RESULTS: It was observed that the values for sag-related deflection were
      significantly less for the 'as cast' samples of all the alloy groups.
      Nickelchromium (NiCr) and cobaltchromium (CoCr) exhibited value of 19.4 MUm and
      14.8 MUm, respectively. CONCLUSION: Among the four groups of alloys tested, CoCr
      based alloy exhibited the least amount of sag-related deflection. The results
      show that the sag-related deflection was less in Co-Cr alloys as compared with
      the NiCr alloys, still Ni-Cr alloys in fixed dental prostheses frameworks are
      used due to their desirable physical and chemical properties.

PMID- 24669056
TI  - Journal scan.

PMID- 24669057
TI  - Outcome of external cephalic version in breech presentation.

PMID- 24669058
TI  - Immunoglobulin G and immunoglobulin M anti-Helicobacter pylori antibodies
      diagnostic and prognostic value in gastritis.

PMID- 24669059
TI  - Managing urethral injuries in suburban India-general surgeon's perspective.
AB  - Although, urethral injuries are relatively uncommon, their incidence has been
      increasing due to increasing incidence of road traffic accidents. Initial
      management of urethral injury depends upon the degree and location of the injury,
      patients' haemodynamic status, and any associated injuries. Besides these
      factors, availability of clinical infrastructure and clinical expertise also play
      a significant role in making appropriate management decisions at the time of
      injury. 

PMID- 24669061
TI  - Journal scan.

PMID- 24669060
TI  - Management of effects of heat-need for change.

PMID- 24669062
TI  - Unilateral pulmonary agenesis-a rare cause of respiratory distress in infancy.

PMID- 24669064
TI  - Ovarian endometriosis with co-existing granulomatous inflammation-a rare
      association.

PMID- 24669063
TI  - Enhanced aesthetics with metal-free ceramics and post systems-case reports.

PMID- 24669065
TI  - A case of decompression illness during saturation diving.

PMID- 24669066
TI  - An interesting case of grenade blast splinter injury-in peace.

PMID- 24669067
TI  - What is the diagnosis?

PMID- 24669068
TI  - Live adult filarial worm in a scrotal swelling-a case report.

PMID- 24669069
TI  - Experience with a versatile anaesthesia machine.

PMID- 24669070
TI  - Dental issues among divers.

PMID- 24669072
TI  - Malplacement of endocardial pacemaker lead in the left ventricle.

PMID- 24669073
TI  - Ventilator-associated pneumonia in advanced lung disease: A wakeup call.

PMID- 24669074
TI  - Impact of ventilator associated pneumonia on outcome in patients with chronic
      obstructive pulmonary disease exacerbation.
AB  - BACKGROUND AND OBJECTIVE: There are sparse data regarding the impact of
      ventilator-associated pneumonia (VAP) on outcome among patients with chronic
      obstructive pulmonary disease (COPD) exacerbation. MATERIALS AND METHODS: This
      retrospective study included patients with COPD exacerbation requiring
      endotracheal intubation for more than 48 h admitted in a single respiratory unit
      from January 2008 to December 2009. Records of these patients were checked for
      the occurrence of VAP. RESULTS: One hundred and fifty-three patients required
      endotracheal intubation for COPD exacerbation during this period. The mean age of
      this cohort was 61.46 +/- 11.3 years. The median duration of COPD was 6 years
      (range: 1-40). A total of 35 (22.8%) patients developed VAP (early: 9 and late:
      26). The risk of mortality was comparable between two groups, that is, patients
      with and without VAP [odd's ratio (OR)-1.125; 95% confidence interval (CI), 0.622
      2.035]. The duration of mechanical ventilation and hospital stay (median +/-
      standard error, 95% CI) was 32 +/- 10 (95% CI, 13-51) versus 10 +/- 2 (95% CI, 6
      14) days; P <= 0.001 and 53 +/- 26 (95% CI, 3-103) versus 18 +/- 7 (95% CI, 5-31)
      days; P = 0.031, respectively was higher among patients with VAP. CONCLUSIONS:
      Our study has shown that VAP leads to increased duration of mechanical
      ventilation and hospital stay; however, the mortality is not affected.

PMID- 24669075
TI  - Therapeutic rigid bronchoscopy at a tertiary care center in North India: Initial
      experience and systematic review of Indian literature.
AB  - BACKGROUND AND AIM: Rigid bronchoscopy is often an indispensable procedure in the
      therapeutic management of a wide variety of tracheobronchial disorders. However,
      it is performed at only a few centers in adult patients in India. Herein, we
      report our initial 1-year experience with this procedure. MATERIALS AND METHODS:
      A prospective observational study on the indications, outcomes, and safety of
      various rigid bronchoscopy procedures performed between November 2009 and October
      2010. Improvement in dyspnea, cough, and the overall quality of life was recorded
      on a visual analog scale from 0 to 100 mm. A systematic review of PubMed was
      performed to identify studies reporting the use of rigid bronchoscopy from India.
      RESULTS: Thirty-eight rigid bronchoscopies (50 procedures) were performed in 19
      patients during the study period. The commonest indication was benign tracheal
      stenosis followed by central airway tumor, and the procedures performed were
      rigid bronchoplasty, tumor debulking, and stent placement. The median procedure
      duration was 45 (range, 30-65) min. There was significant improvement in quality
      of life associated with therapeutic rigid bronchoscopy. Minor procedural
      complications were encountered in 18 bronchoscopies, and there was no procedural
      mortality. The systematic review identified 15 studies, all on the role of rigid
      bronchoscopy in foreign body removal. CONCLUSIONS: Rigid bronchoscopy is a safe
      and effective modality for treatment of a variety of tracheobronchial disorders.
      There is a dire need of rigid bronchoscopy training at teaching hospitals in
      India.

PMID- 24669076
TI  - Treatment pathways of extrapulmonary patients diagnosed at a tertiary care
      hospital in Delhi, India.
AB  - BACKGROUND: In order to put extrapulmonary tuberculosis patients early on
      treatment, it is important to study pathways, which these patients adopt in for
      seeking treatment. MATERIALS AND METHODS: In order to study the treatment
      pathways of extrapulmonary patients and assess appropriate points for
      intervention, a cross-sectional study was conducted in chest clinic of a tertiary
      care hospital in Delhi. RESULTS: Factors associated with longer paths included
      reason for going to first health facility (nearness and known provider), availing
      more than one health facilities, presenting symptoms of fever, joint pain,
      nodular skin swelling and skin lesion. Self-referral to the chest clinic was
      associated with shorter paths. Lower level of education, occupation, non-serious
      perception of the disease and visiting five health facilities were significantly
      associated with patient delay of more than 3.5 weeks. Symptoms of fever, joint
      pain and skin lesion, visiting private health facility first, availing more than
      two health facilities and travelling distance of more than 100 km to reach chest
      clinic were significantly associated with the health facility delay of more than
      4.5 weeks. CONCLUSIONS: Increasing public awareness, training of private
      practitioners and capacity building of government facilities will help in
      reducing delay.

PMID- 24669077
TI  - Clinicopathological and immunohistochemical profile of non-small cell lung
      carcinoma in a tertiary care medical centre in South India.
AB  - BACKGROUND: Lung cancer is a highly aggressive malignancy causing high morbidity
      and mortality. An increasing incidence of lung cancer has been observed in India.
      Currently, the classification of lung carcinoma has gone beyond small cell lung
      carcinoma and non-small cell lung carcinoma (NSCLC). Precise subtyping of poorly
      differentiated NSCLC into adenocarcinoma and squamous cell carcinoma has a direct
      impact on patient management and prognosis. With this background, many molecules
      are under study for developing targeted therapies. Epidermal growth factor
      receptor (EGFR) is one such biomarker considered to be useful in targeted therapy
      for adenocarcinoma. OBJECTIVE: The aim of this study was to subtype poorly
      differentiated NSCLC based on the expression of thyroid transcription factor-1
      (TTF-1) and p-63 and to evaluate EGFR expression in adenocarcinomas. MATERIALS
      AND METHODS: A retrospective analysis of 84 cases of poorly differentiated
      carcinomas of the lung was performed. Paraffin sections were immunostained with
      TTF-1 and p-63 and the tumors were subtyped. EGFR expression was assessed in
      adenocarcinomas by immunohistochemistry. RESULTS: Fifty-five percent of the NSCLC
      were adenocarcinoma, with a peak incidence between 61 and 70 years of age and a
      male predominance. EGFR was expressed in 89% of the adenocarcinomas. CONCLUSIONS:
      Poorly differentiated non-small cell carcinoma can be subtyped by
      immunohistochemical markers and hence has a direct impact on the current
      therapeutic strategies.

PMID- 24669079
TI  - Reference equations for 6-min walk test in healthy Indian subjects (25-80 years).
AB  - BACKGROUND: Six-min walk test (6MWT), a simple functional capacity evaluation
      tool used globally to determine the prognosis and effectiveness of any
      therapeutic/medical intervention. However, variability in reference equations
      derived from western population (due to racial and ethnicity variations) hinders
      from adequate use of 6MWT clinically. Further, there are no valid Indian studies
      that predict reference values for 6-min walk distance (6MWD) in healthy Indian
      normal. OBJECTIVE: We aimed for framing individualized reference equations for
      6MWT in healthy Indian population. MATERIALS AND METHODS: Anthropometric
      variables (age, weight, height, and body mass index (BMI)) and 6-min walk in a 30
      m corridor were evaluated in 125 subjects (67 females) in a cross-sectional
      trial. RESULTS: 6MWD significantly correlated with age (r = -0.29), height (r =
      0.393), weight (r = 0.08), and BMI (r = -0.17). The gender specific reference
      equations for healthy Indian individuals were: (1) Males: 561.022 - (2.507 * age
      [years]) + (1.505 * weight [kg]) - (0.055 * height [cm]). R (2) = 0.288. (2)
      Indian females: 30.325 - (0.809 * age [years]) - (2.074 * weight [kg]) + (4.235 *
      height [cm]). R (2) = 0.272. Though the equations possess a small coefficient of
      determination and larger standard error estimate, the former applicability to
      Indian population is justified. CONCLUSION: These reference equations are
      probably most appropriate for evaluating the walked capacity of Indian patients
      with chronic diseases.

PMID- 24669078
TI  - Correlation of BMI and oxygen saturation in stable COPD in Northern India.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with
      clinically relevant extra pulmonary manifestations; one of them is weight loss.
      However, there are very few studies from North India available in relation to
      body mass index (BMI) and Oxygen saturation (SpO2) with COPD. AIMS: To study the
      prevalence of undernutrition among stable COPD patients and correlation of COPD
      severity with SpO2 and BMI. SETTINGS AND DESIGN: A prospective study was carried
      out at a tertiary care hospital. SUBJECTS AND METHODS: COPD patients were
      diagnosed and staged as per global initiative for chronic obstructive lung
      disease (GOLD) guidelines. SpO2 was measured using pulse oxymeter and BMI
      categorization was done as per new classification for Asian Indians (2009).
      Statistical analysis was done using Statistical Package for Social Sciences
      Version 15.0. RESULTS: Out of 147 COPD patients, 85 (57.8%) were undernourished.
      The prevalence of undernourished BMI was 25%, 50.8%, 61.7%, and 80% in stage I,
      II, III and IV respectively; statistically significant (P < 0.050). The mean SpO2
      was 95.50 +/- 1.41, 95.05 +/- 2.42, 94.37 +/- 2.28 and 93.05 +/- 1.39 in stage I,
      II, III and IV respectively; statistically significant (F = 4.723; P = 0.004).
      CONCLUSIONS: The overall prevalence of under nutrition among COPD patients was
      57.8%. With increasing COPD stage the BMI and median SpO2 value decreased in
      progressive manner. Association of SpO2 and COPD stages could be explored further
      in order to suggest an additional marker of disease severity that would add a new
      dimension in the management of COPD.

PMID- 24669080
TI  - Effect of cigarette smoking on nasal mucociliary clearance: A comparative
      analysis using saccharin test.
AB  - BACKGROUND: Nasal mucociliary clearance (NMC) system transports the mucus layer
      covering the nasal epithelium towards nasopharynx by ciliary beating at a
      frequency of 7-16 Hz. NMC is altered by septal deviations, upper respiratory
      infections, and drugs. Few studies have revealed significant depression of
      ciliary activity in smokers. We conducted this study to compare NMC and influence
      duration of smoking on NMC in adult smokers and nonsmokers using saccharin test.
      MATERIALS AND METHODS: Our study included 30 nonsmokers and 30 smokers (21-40
      years) who were not on any medications and had no history of any systemic
      illness. Time elapsing until the first experience of sweet taste at posterior
      nasopharynx, following placement of saccharin particle approximately 1 cm behind
      the anterior end of inferior turbinate was recorded as NMC time in minutes using
      standard method described by Anderson. Mean NMC of both groups were compared
      using Student's t-test and influence of duration was analyzed by one-way Analysis
      of variance (ANOVA). RESULTS: NMC was significantly prolonged in smokers (481.2
      +/- 29.83; P < 0.01) in comparison to nonsmokers (300.32 +/- 17.42 s). A
      statistically significant increase in NMC was observed with an increase in
      duration of smoking habit (NMC in smoking <1 year = 492.25 +/- 79.93 s, 1-5 years
      = 516.7 +/- 34.01 s, >5 years = 637.5 +/- 28.49 s; F statistic = 20.8968, P =
      0.0000). CONCLUSIONS: NMC measurement is a simple and useful index for the
      assessment of effect of smoking on the ciliary activity of respiratory mucosa.
      Prolonged clearance observed in smokers of our study may be due to slowed ciliary
      beat frequency or reduction in number of cilia and changes in viscoelastic
      properties of mucus.

PMID- 24669082
TI  - Ambroxol hydrochloride in the management of idiopathic pulmonary fibrosis:
      Clinical trials are the need of the hour.
AB  - Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease of unknown
      etiology. Its pathogenesis remains poorly elucidated but aberrant wound healing
      is central to its pathology. It has a median survival time of 3 to 5 years. None
      of the treatment modality or drugs tried in its management has so far changed the
      overall outcome. Recent in vitro and experimental studies have shown that
      ambroxol hydrochloride exerts several newer actions, namely the surfactant
      stimulatory, anti-imflammatory and anti-oxidant actions, in addition to its being
      a secrrtolytic and mucokinetic agent. The anti inflammatory and anti-fibrotic
      properties of the drug are due to its ability to block the release of oxidant
      stress markers, cytokines, leukotrienes, MPO activity, hydroxyproline content,
      nitic oxide and/or collagen I & III mRNA in the local milieu while preserving the
      SOD and GSH-PX activities. In human studies also, the agent was able to block the
      expression of TGF-beta and TNF-alpha in plasma and preserving the carbon monoxide
      diffusion capacity of the lungs in lung cancer patients on radiation therapy.
      Thus, ambroxol may have the potential to check the dysregulated healing process
      that is typical of IPF. This, coupled with its safety profile for human use,
      warrants clinical trials of the drug in the management of IPF. 

PMID- 24669083
TI  - Chylothorax in gastric adenocarcinoma: A case report and systematic review of the
      English literature.
AB  - BACKGROUND: Chylothorax is a rare complication of gastric adenocarcinoma and data
      on its identification, prevalence and outcomes are scant. OBJECTIVES: To enable
      identification of gastric carcinoma as a cause of chylothorax. METHODS: A case
      report and a systematic review were conducted of all reported cases of gastric
      adenocarcinoma with chylothorax as the presenting complaint in the English
      literature. RESULTS: Chylothorax is a rare presenting complaint of gastric
      adenocarcinoma. There are only 18 case reports in the world literature, of which
      six are in English. Chylothorax occurred variably in gastric adenocarcinoma,
      either as a presenting feature or as a complication of therapy. Here, we analyze
      the index case and six patients in whom gastric carcinoma presented with
      chylothorax as the initial symptom. Respiratory features of cough and dyspnea
      preempted any abdominal complaint. Bilateral chylothorax (66%) with associated
      chylous ascites (50%) was common. Four of the six patients had skin lymphedema
      also as a prominent feature. The chylothoraces have been treated by therapeutic
      pleurocentesis, intercoastal tube drainage and restriction of oral intake.
      Gastric adenocarcinoma was associated with high mortality (50%) and morbidity.
      CONCLUSIONS: Chylothorax can be the presenting feature of gastric adenocarcinoma.
      A thorough search for this life-threatening disease should be done before
      labeling the chylothorax as idiopathic.

PMID- 24669084
TI  - Primary pulmonary lymphoma: About five cases and literature review.
AB  - Primary pulmonary lymphoma is a very rare neoplasm that represents only 3-4% of
      extranodal non-Hodgkin lymphoma (NHL), less than 1% of NHL and only 0.5-1% of
      primary pulmonary malignancies. Primary pulmonary NHL is most commonly
      represented by marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
      type (MALT lymphoma). The clinical characteristics, methods of treatment, and
      outcomes are not well-elucidated. We, therefore, reviewed the medical records of
      five Moroccan patients who were pathologically and clinically diagnosed as
      primary pulmonary lymphoma and treated in our institute of oncology. 

PMID- 24669085
TI  - Visceral leishmaniasis with pleural effusion in an immunocompetent patient.
AB  - Visceral leishmaniasis (VL) is usually characterized by splenomegaly, pallor and
      fever. Pleural effusion is an uncommon feature of this disease, which is
      encountered in immunocompromised patients. Here, we report a case of VL with
      pleural effusion in an immunocompetent patient. Pulmonary symptoms in VL are
      usually related to bacterial lung infection, vagal nerve compression by
      splenomegaly, and hypoalbuminaemia with mild pulmonary edema. Our patient
      presented with cough and chest pain. The clinical features of this case were
      baffling since they mimicked that of pulmonary tuberculosis. This case report
      emphasizes the need to recognize the diverse nature of presentation of this
      curable yet fatal infectious disease. 

PMID- 24669086
TI  - A case of concomitant Hodgkin's lymphoma with tuberculosis.
AB  - Tuberculosis (TB) presenting with Hodgkin's Lymphoma is a rare and difficult
      clinical situation for any physician to identify and to manage because of very
      similar clinical presentation. Herein we report a case of 29 year old woman who
      presented with enlarged lymph nodes, diagnosed and initiated on therapy for TB,
      based on the cervical node biopsy that showed granulomatous lymphadenitis
      suggestive of TB. Despite being on regular isoniazid, rifampicin, pyrazinamide
      and ethambutol regimen, she did not improve but worsened clinically! After an
      extensive work up that included endobronchial ultrasound (EBUS) and
      mediastinoscopy, a diagnosis of Hodgkin's disease of nodular sclerosis type was
      made. She was treated with chemotherapy and radiotherapy along with her TB
      therapy. Patient showed significant improvement following therapy. 

PMID- 24669087
TI  - "Diesel siphoner's lung": Exogenous lipoid pneumonia following hydrocarbon
      aspiration.
AB  - Lipoid pneumonia is an unusual and uncommon form of pneumonia caused by
      aspiration of fatty substances. Hydrocarbon pneumonitis following aspiration of
      diesel is a form of exogenous lipoid pneumonia wherein, aspirated diesel reaches
      the alveoli rapidly without evoking any significant cough, but initiates an
      intense inflammatory reaction in the pulmonary parenchyma. This is a rarely
      described clinical scenario, although the practice of diesel siphonage from
      automobiles is a common practice in developing countries. We herein describe a 40
      year-old male patient, in whom the diagnosis of lipoid pneumonia was delayed for
      a long duration and highlight the importance of taking a detailed occupational
      exposure history in patients with non-resolving pneumonia to rule out the
      underlying possibility of this rare clinical entity. 

PMID- 24669089
TI  - Solitary pulmonary nodule: A rare presentation of pulmonary mucormycosis in an
      immunocompetent adult.
AB  - Pulmonary mucormycosis is a rare opportunistic infection of immunocompromised
      individuals. Here, we report a case of 70-year-old male, smoker presenting with
      high-grade fever for 2 weeks and episodes of hemoptysis. Contrast-enhanced
      computed tomography (CT) thorax revealed a solitary pulmonary nodule measuring
      2.3 * 1.6 cm in the right upper lobe. CT guided fine needle aspiration cytology
      and true cut biopsy showed plenty of typical fungal hyphae consistent with the
      diagnosis of mucormycosis. Fungal culture confirmed the organism as mucor.
      Positron emission tomography-CT scan showed a non- 18 fluorodeoxy glucose avid
      nodule ruling out possibility of malignancy. Investigation did not reveal any
      evidence of immunosuppression. Patient was treated with intravenous liposomal
      amphotericin B for 4 weeks. Follow-up chest X-ray and CT scan after 6 weeks were
      normal. 

PMID- 24669088
TI  - Transtracheal oxygen and positive airway pressure: A salvage technique in overlap
      syndrome.
AB  - The coexistence of sleep apnea-hypopnea syndrome (SAHS) with chronic obstructive
      pulmonary disease (COPD) occurs commonly. This so called overlap syndrome leads
      to more profound hypoxemia, hypercapnic respiratory failure, and pulmonary
      hypertension than each of these conditions independently. Not infrequently, these
      patients show profound hypoxemia, despite optimal continuous positive airway
      pressure (CPAP) therapy for their SAHS. We report a case where CPAP therapy with
      additional in-line oxygen supplementation failed to accomplish adequate
      oxygenation. Adding transtracheal oxygen therapy (TTOT) to CPAP therapy provided
      better results. We review the literature on transtracheal oxygen therapy and how
      this technique may play a significant role in these complicated patients with
      overlap syndrome, obviating the need for more invasive procedures, such as
      tracheostomy. 

PMID- 24669090
TI  - Non-resolving pneumonia: A rare presentation of progressive disseminated
      histoplasmosis.
AB  - Histoplasmosis, a fungal disease caused by Histoplasma capsulatum, is endemic in
      North and South America. Except few scattered cases, the disease is considered to
      be a non-entity in India. Furthermore, disseminated histoplasmosis is rare in the
      immunocompetent individuals. We report an adolescent boy presenting as middle
      lobe consolidation which did not respond to antibiotics. His condition
      deteriorated with the development of mediastinal lymphadenopathy, pleural
      effusion and hepatosplenomegaly. A diagnosis of progressive disseminated
      histoplasmosis was established by his clinical findings as well as bronchoscopic
      biopsy, transbronchial needle aspiration cytology and bronchoalveolar lavage
      culture demonstrating Histoplasma capsulatum. The case represents a unique
      example of progressive disseminated histoplasmosis in an immunocompetent
      individual in India. 

PMID- 24669091
TI  - Mounier-Kuhn syndrome masquerading pulmonary thromboembolism in an elderly male.
AB  - Mounier-Kuhn syndrome, also referred to as tracheobronchomegaly, is a rare
      idiopathic clinical and radiologic disorder characterized by significant
      tracheobronchial dilation. It results in recurrent lower respiratory tract
      infections and bronchiectasis. In severe cases, patients may present with acute
      respiratory distress requiring hospital admission and ventilatory support.
      Clinical examination and chest radiography may be misleading in these patients as
      tracheobronchomegaly is easily overlooked on radiographs. We present an
      interesting report of our patient who presented with acute shortness of breath. A
      diagnosis of acute pulmonary thromboembolism was suggested by initial evaluation.
      Computed tomography pulmonary angiography was negative for thromboembolism;
      however, it revealed diagnosis of this rare disorder. 

PMID- 24669092
TI  - A rare case of calcified pulmonary aspergilloma.
AB  - Pulmonary aspergilloma is caused by colonization and proliferation of Aspergillus
      in the preexisting cavities in lungs. Diagnosis of pulmonary aspergilloma is
      usually made based on chest X-ray findings, presence of serum precipitins against
      aspergillus and sputum culture. Bronchoscopic visualization of aspergilloma is
      very infrequent and more over calcification is rarely seen. We report a case of
      pulmonary aspergilloma, which was both calcified and visualized endoluminally
      during bronchoscopy. 

PMID- 24669093
TI  - Choking after blunt trauma and an interesting radiological finding.

PMID- 24669094
TI  - Recurrent Sino: Pulmonary infections in an infertile male.

PMID- 24669095
TI  - Pleural effusion masquerading as pseudotumor.

PMID- 24669096
TI  - Biphasic pulmonary blastoma: An unusual presentation with chest wall, rib, and
      pleural involvement.

PMID- 24669097
TI  - Lenalidomide-induced diffuse alveolar hemorrhage.

PMID- 24669098
TI  - DR-70 immunoassay and malignant pleural effusion.

PMID- 24669099
TI  - Authors' reply.

PMID- 24669100
TI  - Plastic bronchitis in beta thalassemia minor.

PMID- 24669101
TI  - Authors' reply.

PMID- 24669102
TI  - Extensive unilateral pulmonary tuberculosis with segmental atresia of principal
      bronchus.

PMID- 24669103
TI  - Septal pacing of right ventricle: has the last word been said?

PMID- 24669104
TI  - A novel method of placing right ventricular leads in patients with persistent
      left superior vena cava using a conventional j stylet.
AB  - BACKGROUND: Locating pacemaker electrodes can become complicated by congenital
      abnormalities such as persistent left superior vena cava (LSVC). OBJECTIVE: To
      evaluate a technique for the implanting of ventricular electrode in patients with
      persistent LSVC. MATERIALS AND METHODS: The study was carried out from June 2001
      to June 2010 involving all patients who were admitted to the Hospital
      Universitario Mayor, Instituto de Corazon de Bogota and Hospital Universitario
      Clinica San Rafael (Bogota-Colombia) for implanting pacemakers or cardiac
      defibrillators. LSVC was diagnosed by fluoroscopic observation (anterior
      posterior view) of the course of the stylet. Four steps were followed: 1) Move
      the electrode with a straight stylet to the right atrium. 2) Change the straight
      stylet by a conventional J stylet and push the electrode to the lateral or
      anterolateral wall of the right atrium. 3) Remove the guide 3-5 cm and 4) Push
      the electrode which crosses the tricuspid valve into the right ventricle and
      finally deploy the active fixation mechanism. RESULTS: A total of 1198 patients
      were admitted for pacemaker or cardiac defibrillator implant during the 9-year
      study period, 1114 received a left subclavian venous approach. There were 573
      males and 541 females. Persistent LSVC was found in five patients (0.45%)
      Fluoroscopy time for implanting the ventricular electrode ranged from 60 to 250
      seconds, 40 to 92 minutes being taken to complete the whole procedure.
      CONCLUSION: We present a simple and rapid technique for electrode placement in
      patients with LSVC using usual J guide and active fixation electrodes with high
      success.

PMID- 24669105
TI  - An approach to the stepwise management of severe mitral regurgitation with
      optimal cardiac pacemaker function.
AB  - Right ventricular apical pacing may cause or worsen mitral regurgitation (MR).
      Potential mechanisms for this adverse sequelae include intraventricular
      dyssynchrony, altered papillary muscle function, pacing-induced cardiomyopathy
      with left ventricular dilation, and annular dilation. In contrast, biventricular
      (BiV) pacing may improve MR presumably by opposing the negative effects. Whether
      or not left ventricular lead location is important in treating mitral
      regurgitation in patients with pacemakers is unknown. We report a case of severe
      MR and left ventricular (LV) systolic failure in a patient with right ventricular
      pacing. Multiple potential etiologies for the worsening valve function were
      noted, and a stepwise iterative optimizing scheme that included basal lateral LV
      pacing improved mitral valve function and ameliorated heart failure symptoms. 

PMID- 24669106
TI  - Normal heart ventricular tachycardia associated with pregnancy: successful
      treatment with catheter ablation.
AB  - BACKGROUND: Normal heart ventricular arrhythmia occurring during pregnancy has
      been previously described. Whilst there are established reports of catheter
      ablation to treat supraventricular arrhythmia during pregnancy, there are no
      reports of ablation to treat ventricular tachycardia. CASE: We present the case
      of a 36 year old women, 31 weeks into an otherwise uncomplicated pregnancy,
      experiencing significant, troublesome and drug refractory tachycardia emanating
      from the right ventricular outflow tract. CONCLUSION: We describe a successful
      radio frequency ablation in the third trimester of pregnancy.

PMID- 24669107
TI  - Close Proximity of Left Anterior Descending Artery to the Right Ventricular Lead
      Apparently Implanted into the Mid-septum.
AB  - Right ventricular (RV) mid-septal pacing should have fewer negative effects on
      left ventricular function compared to apical pacing. However, targeting the mid
      septum may be technically challenging since it is usually done with two
      dimensional fluoroscopy. The rotation of the heart and various shapes of the RV
      make it difficult to assess, whether the lead is really anchored in the septum.
      Many leads, apparently anchored in the septum, are in fact anchored in the
      anterior wall or anteroseptal groove, and some can get anchored in close
      proximity to the left anterior descending artery (LAD). We report three cases
      from our series of 51 patients, in whom the RV lead thought to be implanted in
      the mid-septum was in fact anchored in close proximity of LAD when assessed using
      computed tomography. 

PMID- 24669108
TI  - Epicardial ablation: prevention of phrenic nerve damage by pericardial injection
      of saline and the use of a steerable sheath.
AB  - Because of the close proximity of the phrenic nerve to the pericardium, phrenic
      nerve damage caused by epicardial ablation can easily occur. We report two cases
      of epicardial VT ablation where pericardial injection of saline, combined with
      the use of a steerable sheath, successfully prevents the phrenic nerve from being
      damaged. 

PMID- 24669109
TI  - An Alternative Way to Reach the Epicardial Focus of the Left Ventricular
      Tachycardia in a Patient with Non-ischemic Cardiomyopathy.
AB  - We report a case of a 69-year-old male with non-ischemic cardiomyopathy, having
      drug- and antitachycardia pacing-refractory ventricular tachycardia resulted in
      multiple ICD shocks. The sustained and intractable ventricular arrhythmia was
      mapped and ablated with the aid of the three-dimensional electroanatomic mapping
      system, initially performed but unsuccessful from the endocardial site then
      performed successfully from the epicardial site via the coronary sinus. 

PMID- 24669110
TI  - Diagnostic dilemmas for underlying pathophysiology of arrhythmias originating
      from the right ventricle.

PMID- 24669111
TI  - Right ventricular ablation as a therapeutic option for left ventricular
      hypertrabeculation / noncompaction.

PMID- 24669112
TI  - Arrhythmogenic Right Ventricle in Left Ventricular Non-compaction - In Response
      to the Letter to the Editor "Diagnostic Dilemmas for Underlying Pathophysiology
      of Arrhythmias Originating from the Right Ventricle".

PMID- 24669113
TI  - Arrhythmogenic Right Ventricle in Left Ventricular Non-compaction - In response
      to "Right Ventricular Ablation as a Therapeutic Option for Left Ventricular
      Hypertrabeculation / noncompaction".

PMID- 24669114
TI  - The role of Ibn Sina (Avicenna)'s medical poem in the transmission of medical
      knowledge to medieval Europe.
AB  - The Medical Poem ("Al-Urjuzah Fi Al-Tibb") of Ibn Sina (Avicenna, 980-1037), is
      the subject of this primary-source study evaluating its scientific value, poetics
      and pedagogical significance as well as assessing its role in the transmission of
      medical knowledge to Medieval Europe. In addition to one original manuscript and
      two modern editions, the English translation by Krueger was also studied. Ibn
      Sina's poem on medicine consisting of meticulously classified 1326 verses, can be
      considered as a poetic summary of his encyclopedic textbook: The Canon of
      Medicine; hence its popularity in the East then the West as a tool in the process
      of transmitting medical knowledge from master to student. Since first translated
      by Gerard of Cremona (1114-1187) in the middle of the 12(th) century, the
      Latinized poem was frequently published in Medieval Europe either independently
      or combined with the Latinized Canon of Medicine or with the Articella; the
      famous collection of Greco-Roman and Latinized Arabian medical treatises in use
      in the universities of Salerno, Montpelier, Bologna and Paris up to the 17(th)
      century. The study of the Krueger's English edition revealed few places where the
      full meanings of the original Arabic text were not conveyed. A list of those
      places is given together with the suggested corrections. 

PMID- 24669115
TI  - Current practices in fertility preservation in male cancer patients.
AB  - The incidence of a cancer diagnosis in children and young adolescents is
      increasing. With better treatments, the number of young cancer survivors living
      through reproductive age is increasing. Fertility preservation of these men and
      women has become essential and needs to be discussed prior to the start of cancer
      treatment. Here we review the current guidelines for male oncofertility patients
      and highlight some of the important gonadotoxic effects of chemotherapy,
      radiotherapy and surgery. Options for fertility preservation are also discussed
      along with resources that should be made available to all patients. 

PMID- 24669116
TI  - Palliative chemotherapy in carcinoma penis: Does platinum and taxane combination
      holds a promise?
AB  - AIM: To report safety and efficacy of chemotherapy incorporating the combination
      of paclitaxel and platinum in patients with advanced penile carcinoma. MATERIALS
      AND METHODS: Retrospective analysis of patient with advanced penile carcinoma
      undergoing palliative chemotherapy with paclitaxel and platinum combination. The
      demographic profile, indication of treatment, chemotherapy details, toxicity and
      survival outcome were noted. Statistical analysis was done for estimation of
      progression free survival and overall survival. Factors affecting these outcomes
      were sought for. RESULTS: Eighteen patients with a median age of 47.5 years (31
      68 years) were offered palliative intent chemotherapy over a period of 2.5 years.
      ECOG performance was 1 in 12 patients (66.7%) and 2 in 6 patients (33.3%). The
      grade of tumor was poorly differentiated in 8 patients (44.4%), moderately
      differentiated in 5 (27.8%) and we1l differentiated in 5 patients (27.8%). Twelve
      patients had previous surgical treatment (66.7%), with 2 of them having received
      groin radiation in past. The indication for treatment was metastatic disease in 7
      patients (38.9%) and locally advanced disease in 11 patients (61.1%). Out of 18
      patients 13 received chemotherapy. Paclitaxel and carboplatin combination was
      given in 10 patients (76.9%) while paclitaxel and cisplatin was received by 3
      patients (23.1%). The median numbers of cycles received were 3 (1-6 cycles).
      Response rate was 30.8%. The median estimated progression free survival (PFS) and
      overall survival (OS) for patients receiving atleast one cycle of chemotherapy (n
      = 13) were 96 days and 246 days respectively. Among tested variables the median
      OS in patients who had received 2 or more cycles was 351 days versus 55 days in
      those who received less than 2 cycles (P = 0.025). However, after applying
      Bonferroni correction, the difference was no longer significant. There was no
      toxicity related death or life threatening complication. CONCLUSION: Our
      institutional protocol of platinum-based doublet with paclitaxel is effective,
      well-tolerated and has the advantage being delivered on an outpatient basis
      alone. Overall, we believe that paclitaxel-platinum is an effective regimen that
      needs to be investigated further in larger studies.

PMID- 24669117
TI  - False fracture of the penis: Different pathology but similar clinical
      presentation and management.
AB  - INTRODUCTION: Penile fracture is the most common presentation of acute penis.
      Rupture of the superficial dorsal penile vein (s) may mimic penile fractures with
      similar clinical presentation but with intact corporeal bodies. Our aim of the
      study is to highlight superficial dorsal penile vein (s) injury as true emergency
      with better prognosis. SUBJECTS AND METHODS: Sixty-eight patients with suspected
      penile fractures presented to our hospital between June 2007 and January 2013.
      Out of these, 11 patients showed intact tunica albuginea on exploration with
      injured dorsal penile vein (s) identified. Records of such 11 cases were reviewed
      regarding age, etiology, symptoms, physical signs, findings of surgical
      exploration and post-operative erectile function. RESULTS: All 11 patients were
      injured during sexual intercourse and presented with penile swelling and
      ecchymosis and gradual detumescence. Mild penile pain was encountered in 5 cases
      and the "snap" sound was noted in 2 cases. Examination revealed no localized
      tenderness, or tunical defect. All the patients regained penile potency without
      deformity after surgical ligation of the severed vessels. One patient developed
      penile hypoesthesia. CONCLUSION: Although the classic "snap" sound and immediate
      detumescence are usually lacking in the symptomology of dorsal penile vein
      rupture, its clinical presentation can be indistinguishable from true penile
      fracture. Surgical exploration is still required to avoid missing tunical tear
      with possible future complications. The long-term outcome and prognosis are
      excellent.

PMID- 24669118
TI  - Predictors of viable germ cell tumor in postchemotherapeutic residual
      retroperitoneal masses.
AB  - OBJECTIVE: The aim of this study was to identify predictors of viable germ cell
      tumor (GCT) in postchemotherapeutic residual retroperitoneal masses. MATERIALS
      AND METHODS: The pertinent clinical and pathologic data of 16 male patients who
      underwent postchemotherapeutic retroperitoneal lymph node dissection (PC-RPLND)
      at King Faisal Specialist Hospital and Research Centre between 1994 and 2005 were
      reviewed retrospectively. It was found that all patients received cisplatin-based
      chemotherapy for advanced testicular GCT. RESULTS: Out of the 16 male patients, 2
      (13%), 8 (50%), and 6 (37%) had viable GCT, fibrosis, and teratoma, respectively.
      Ten (10) of the patients with prechemotherapeutic S1 tumor markers did not have
      viable GCT, and two of the six patients who had prechemotherapeutic S2 tumor
      markers have viable GCT. All tumor marker levels normalized after chemotherapy
      even in patients with viable GCT. Four patients had vascular invasion without
      viable GCT. Furthermore, four patients had more than 60% embryonal elements in
      the original pathology, but only 1 had viable GCT at PC-RPLND. Four of the five
      patients with immature teratoma had teratoma at PC-RPLND but no viable GCT;
      however, out of the four patients with mature teratoma, one had viable GCT and
      two had teratoma at PC-RPLND. Of the two patients with viable GCT, one had 100%
      embryonal cancer in the original pathology, prechemotherapeutic S2 tumor markers,
      history of orchiopexy, and no vascular invasion; the other patient had yolk sac
      tumor with 25% embryonal elements and 40% teratoma in the original pathology, and
      prechemotherapeutic S2 tumor markers. CONCLUSION: None of the clinical or
      pathological parameters showed a strong correlation with the presence of viable
      GCT in PC-RPLND. However, patients with >=S2 may be at higher risk to have viable
      GCT. Further studies are needed to clarify this.

PMID- 24669119
TI  - Clinical predictors of nocturia in the sleep apnea population.
AB  - OBJECTIVES: This study aims to evaluate clinical predictors of nocturia in
      patients with obstructive sleep apnea (OSA). MATERIALS AND METHODS: In
      retrospective manner, a total of 200 patients with OSA were randomly included.
      Group I contained 100 patients with OSA and no nocturia, and Group II included
      100 patients with OSA and nocturia. Bivariate logistic analyses were used to
      identify variables most likely to contribute to nocturia. Multivariate logistic
      regression of age, waist circumference, STOP score (Snore, Tired, Obstruction and
      Pressure), and Apnea-Hypopnea Index (AHI) was performed to evaluate predictors of
      nocturia. Statistical significance was defined as P < 0.05. RESULTS: Median
      nocturia episodes were 2.2 in Group II. Patients were younger in Group I, with a
      mean age of 45 vs 50 years (P = 0.008). Mean BMI of 30 was similar in both
      groups, but there were more overweight patients in Group II (28% vs 18%). AHI
      approached significance between groups-18 vs 23 in group I and II, respectively
      (P = 0.071). In multivariate analysis, age over 70 years and moderate AHI were
      statistically significant predictors of nocturia (coefficients 0.6 and -0.2 with
      P = 0.003 and 0.03, respectively). CONCLUSIONS: This study identifies age and AHI
      score as predictors of nocturia in patients with OSA. This may indicate the
      usefulness of incorporating nocturia in the screening of patients with OSA.
      Future studies are needed to further evaluate mechanism of action, clinical
      significance, and effect of treatment for nocturia in patients with OSA.

PMID- 24669120
TI  - Antenatal diagnosis, prevalence and outcome of congenital anomalies of the kidney
      and urinary tract in Saudi Arabia.
AB  - OBJECTIVE: To study the prevalence, pattern of distribution, and the outcome of
      different types of kidney and urinary tract anomalies (CAKUT) diagnosed during
      the antenatal period. The second objective is to test the accuracy of antenatal
      diagnosis of CAKUT. MATERIALS AND METHODS: In a cross-sectional hospital-based
      study, all cases diagnosed antenatally with urinary tract anomalies at King
      Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia, were
      studied. The prevalence, pattern of distribution, and immediate postnatal
      outcomes, in addition to the accuracy of antenatal diagnosis, of those cases are
      reported. RESULTS: One hundred and forty-one cases of urinary tract anomalies
      were antenatally diagnosed; postnatal diagnosis was confirmed in 128 cases
      (90.1%). The prevalence of CAKUT in our population is 3.26 per 1000 births. The
      most common abnormalities detected were hydronephrosis, polycystic kidney
      disease, multicystic dysplastic kidney, and renal agenesis, in descending order
      of frequency. The perinatal mortality rate among fetuses with CAKUT is 310 per
      1000, the majority of these cases (90%) occurred in cases with renal parenchyma
      involvement. CONCLUSIONS: The prevalence of different types of CAKUT is higher
      than that reported in developed countries. Urinary tract anomalies can be
      accurately diagnosed and classified in the antenatal period using ultrasonography
      imaging. Antenatal diagnosis is a helpful tool in planning immediate postnatal
      care and deciding the place for delivery. This might prevent or slow renal
      function deterioration and help in early identification of patients who need
      early surgical intervention.

PMID- 24669121
TI  - A single-center study examining the outcomes of percutaneous epididymal sperm
      aspiration in the treatment of obstructive azoospermia.
AB  - INTRODUCTION: Obstructive azoospermia (OA) is characterized by normal
      spermatogenesis and the absence of sperm in the ejaculate. Variable success rates
      have been reported using in-vitro fertilization (IVF) combined with PESA in cases
      of men with OA. AIMS: To determine fertilization and pregnancy outcomes from PESA
      derived spermatozoa and to ascertain whether frozen spermatozoa yields similar
      outcomes compared to fresh specimens. MATERIALS AND METHODS: The charts of 68
      consecutive couples undergoing 68 cycles of sperm retrieval for OA over eight
      years (2002-2010) were retrospectively reviewed. Patients requiring testicular
      intervention were excluded (n = 17). RESULTS: Viable sperms were identified in
      100% of men, and fresh spermatozoa were obtained in 40 patients (78.4%)
      simultaneously with female egg retrieval. The average fertilization rate was
      77.7% with five embryos not surviving to transfer (12.5%). Pregnancies were
      confirmed in 48.6% (17/35). Twin gestations occurred in 11.8% (2/17) of cases.
      Frozen-thawed spermatozoa were used in 11 patients (21.6%). In this subgroup, the
      average fertilization rate was 73.6% with pregnancies confirmed in 54.5% (6/11).
      No multiple gestations were generated, and no complications occurred. The use of
      fresh spermatozoa for PESA provided no significant improvements in outcomes over
      frozen specimens. SUMMARY: PESA is a very effective, simple, and safe method of
      obtaining spermatozoa for IVF. Outcomes obtained using fresh and frozen PESA
      derived spermatozoa were similar and as such, either could be used during the IVF
      process.

PMID- 24669123
TI  - An evaluation of the efficacy of different doses of ketamine for treatment of
      catheter-related bladder discomfort in patients underwent urologic surgery: A
      prospective, randomized, placebo-controlled, double-blind study.
AB  - BACKGROUND: Urinary catheterization might have catheter-related bladder
      discomfort (CRBD). We evaluated the efficacy of different doses of ketamine in
      comparison to placebo as a treatment of CRBD. MATERIALS AND METHODS: One hundred
      twenty patients who were candidate for urological surgery requiring
      catheterization of the urinary bladder were randomly divided into four groups
      including 30 patients in each. Group I received normal saline, Group II received
      ketamine 150 MUg/kg/iv, Group III received ketamine 200 MUg/kg/iv, and Group IV
      received 250 MUg/kg/iv in the equal volume of 2 mL. The patients were observed
      for each 15 min in the recovery room and in the 1 h, 2 h, 6 h, 12 h, and 24 h
      after discharging from it for severity of CRBD and pain, levels of sedation, and
      post-operative nausea and vomiting. RESULTS: The severity of CRBD at the recovery
      room was significantly reduced in Group III and Group IV after 24 h compared with
      Group I and Group II (P < 0.05). There was no significant difference between
      Group III and Group IV in this respect. The median sedation level was
      significantly lower in 15 min and 30 min after arrival to the recovery in Group
      III and Group IV compared with Group I and Group II (P < 0.05). There was no
      significant difference between Group III and Group IV in this regard.
      CONCLUSIONS: Ketamine 200 MUg/kg/iv had similar efficacy with ketamine 250
      MUg/kg/iv in reducing the severity of CRBD without occurring significant side
      effect.

PMID- 24669122
TI  - The protective effects of pomegranate extracts against renal ischemia-reperfusion
      injury in male rats.
AB  - AIM: To evaluate the possible protective effect of pomegranate extract (PE) on
      rats following renal ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS:
      Twenty-four Wistar rats were divided into three groups. Sham group underwent
      laparotomy then waited for 45 minutes without ischemia. I/R group were subjected
      to left renal ischemia for 45 minutes followed by 60 minutes of reperfusion. I/R
      + PE group were subjected to the same renal I/R as the I/R group were also given
      225 mg/kg PE peroral 30 minutes prior to the ischemia. Malondialdehyde (MDA),
      total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative
      stress index (OSI) were determined on the blood samples and kidney tissues.
      Histopathological analyses were conducted on the kidney tissues. RESULTS: Serum
      TAC levels were significantly decreased in I/R group when compared with S group
      (P = 0.001). Serum MDA levels were increased in I/R group; however, it was not
      statistically significant. In rat kidney tissues, TOS levels and OSI index were
      significantly increased after I/R injury, while TAC levels were decreased. In I/R
      + PE group, PE reversed the negative effects of I/R injury. PE pretreatment was
      effective in decreasing tubular necrosis score. CONCLUSION: PE pretreatment
      ameliorated the oxidative damage and histopathological changes occurring
      following renal I/R injury.

PMID- 24669124
TI  - Wrong site surgery! How can we stop it?
AB  - INTRODUCTION: "Primum non nocere" (first do no harm): Hippocrates (c. 460 BC-377
      BC). Wrong site surgery is the fourth commonest sentinel event after patient
      suicide, operative and post-operative complications, and medication errors.
      Misinterpretation of the clinic letters or radiology reports is the commonest
      reason for the wrong site being marked before surgery. MATERIALS AND METHODS: We
      analyzed 50 cases each of operations carried out on the kidney, ureter, and the
      testis. The side mentioned on clinic letters, the consent form, and radiology
      reports lists were also studied. The results were analyzed in detail to determine
      where the potential pitfalls were likely to arise. RESULTS: A total of 803 clinic
      letters from 150 cases were reviewed. The side of disease was not documented in
      8.71% and five patients had the wrong side mentioned in one of their clinic
      letters. In the radiology reports, the side was not mentioned in three cases and
      it was reported wrongly in two patients. No wrong side was ever consented for and
      no wrong side surgery was performed. CONCLUSION: The side of surgery was not
      always indicated in clinic letter, theatre list, or the consent form despite the
      procedure being carried on a bilateral organ. As misinterpretation is a major
      cause of wrong side surgery, it is prudent that the side is mentioned every time
      in every clinic letter, consent form, and on the theatre list. The WHO surgical
      safety checklist has already been very effective in minimizing the wrong site
      surgery in the National Health Service.

PMID- 24669125
TI  - Status of Her2 over expression in muscle invasive urothelial bladder carcinoma:
      Report of 21 cases.
AB  - BACKGROUND: Invasive urothelial bladder carcinomas have a poor prognosis even
      with cystectomy and chemotherapy. A high number of these patients have Her2
      overexpression. The goal of this study is to assess the Her2 status in muscle
      invasive urothelial bladder carcinoma, to evaluation heterogeneity and
      discordance with metastases. PATIENTS AND METHODS: We retrospectively analyzed 21
      specimens of transurethral resection or cystectomy in patients with invasive
      urothelial bladder carcinoma. We selected one representative section from primary
      tumors and metastases for immunohistochemistry analysis. Staining was evaluated
      according to the same criteria of breast cancer. A chromogenic in situ
      hybridization (CISH) was performed in case of 2+ score or in heterogeneous
      samples. RESULTS: Median age of our patients was 62 years. Intratumoral
      heterogeneity was observed in 2 cases (less than 1%). One case showed a Her2 3+
      score (high grade, pT2 stage) and 3 cases showed a 2+ score (all low grades,
      stage T2, T4, M1, respectively). Two metastatic lymph nodes scored 1+ for the
      first (primary 1+) and 2+ for the second (primary 1+). Two cases showed CISH gene
      amplification. The first one scored 2+ and had area of 3+ score. The second one
      scored 1+ and had area with 2+ score. Four patients died from disease, one of
      them had Her2 3+ score. CONCLUSION: Her2 overexpression can be observed in muscle
      invasive urothelial bladder carcinoma in an important number of patients.
      Evaluation criteria must be standardized, especially with heterogeneous cases.
      Metastases tests can also readdress the expression of Her2, which gives the
      patient a supplementary therapeutic tool.

PMID- 24669126
TI  - Retrovesical hydatid cyst presenting with urinary retention and left kidney
      atrophy.
AB  - Hydatid disease of the urinary tract is uncommon, accounting for only 2-3% of
      cases. There are very few reported cases in the literature of pelvic hydatid
      cysts causing obstructive uropathy and renal failure. We report a case of pelvic
      hydatid cyst in a patient presenting with urinary retention and secondary
      complete atrophy of one kidney. The patient was treated with surgical excision of
      this large retrovesical cyst, along with a simple left nephroureterectomy, with
      rapid improvement of symptoms. Hydatid disease should be taken into consideration
      in the differential diagnosis of a cystic mass in any anatomic localization,
      especially in patients from endemic areas. 

PMID- 24669127
TI  - Retrovesical hydatid cyst presenting with urinary retention and left kidney
      atrophy.

PMID- 24669128
TI  - A case of polypoid and papillary cystitis mimicking an advanced bladder carcinoma
      with invasion of perivesical fat.
AB  - A rare case of polypoid and papillary cystitis without a history of
      catheterization is reported. A 69-year-old man was admitted to our hospital
      because of pain during urination and gross hematuria. The cystscopic and imaging
      findings including ultrasound, CT, and MR image showed an irregular wall
      thickening and stranding in the perivesical fat, which indicated an advanced
      bladder carcinoma, but histopathological findings obtained by transurethral
      resection revealed polypoid and papillary cystitis. Such benign lesions need to
      be discussed in the differential diagnosis of patients with bladder tumor to
      avoid excessive resection. 

PMID- 24669129
TI  - Uncommon causes of anterior urethral diverticula in children: Two cases and
      review of literature.
AB  - Anterior urethral diverticula are rare in children. Anterior urethral valves and
      associated diverticulum is the commonly discussed pathological entity in
      children. There is a lack of awareness among clinicians regarding less common
      presentations of anterior urethral diverticula in children; which can have a
      diverse involvement of the urinary tract. This report describes two uncommon
      presentations of anterior urethral diverticula in children, their diagnoses and
      management. A systematic differential diagnosis and review of anterior urethral
      diverticula in children is also presented. 

PMID- 24669130
TI  - Two rare pathologies of male urethra in children.

PMID- 24669131
TI  - Botryoid-type of embryonal rhabdomyosarcoma of renal pelvis in a young woman.
AB  - A 22-year-old woman presented with three weeks history of intermittent left loin
      pain, on radiological evaluation by U?S and MRI revealed left renal pelvic mass,
      ureterorenoscopy and biopsy taken, but couldn't reveal definitive diagnosis other
      than presence of a malignant process. Left nephroureterctomy was performed.
      Grossly there is a polypoid mass attached to the upper pole of the kidney by
      stalk. Light microscopic examination and immunohistochemical staining confirm a
      diagnosis of Botryoid-type of embryonal rhabdomyosarcoma. Treatment and follow up
      to 1 year is mentioned. Reviewing the literature the presented case is the second
      of this tumor in adult renal pelvis. 

PMID- 24669132
TI  - Surgical reimplantation of penile glans amputation in children during
      circumcision.
AB  - Circumcision is one of the oldest and most commonly performed surgical
      procedures. Unfortunately, various complications may occur during circumcision,
      ranging from trivial to tragic such as penile amputation which is a serious
      complication and a challenging injury to treat. We describe two cases of non
      microsurgical successful reattachment of a distal penile glans which were
      amputated during circumcision. In the first case, a 5-year-old child underwent
      circumcision by an urologist under local anesthesia. In the second one, a 3-year
      old child underwent circumcision by a general practitioner who used to make
      circumcision. In this article, the literature is reviewed; results and potential
      complications of this surgery are also discussed. Glans sensation was present,
      early morning erection was maintained, and there was an erectile response during
      penile manipulation in both cases. Although circumcision is not technically
      difficult, it should be taken seriously. The use of microsurgical reattachment is
      not always possible, especially in pediatric cases; it also requires special
      equipment and training. 

PMID- 24669133
TI  - New compression mechanism in penile-scrotal lymphedema and sexual rehabilitation.
AB  - The objective of this study is to describe a new compression mechanism in the
      treatment of lymphedema of the penis and scrotum and the ensuing sexual
      rehabilitation. The patient, a 58-year-old man, had edema of the penile and
      scrotal region as a result of surgery of the pancreas and spleen and
      chemotherapy. The patient complained of pain, discomfort, and difficulties to
      walk and urinate. A clinical diagnosis of lymphedema of the penis and scrotum was
      reached. Treatment involved the continuous use of a cotton-polyester compression
      garment for the region together with thorough hygiene skin care. The swelling
      reduced significantly within a week to almost a normal aspect which was
      accompanied by clinical improvements of the symptoms. The reduction in penile
      edema allowed sexual rehabilitation even though erectile dysfunction required the
      use of a specific medication (sildenafil). In conclusion, simple and low-cost
      options can improve lymphedema of the penis and scrotum and allow sexual
      rehabilitation. 

PMID- 24669134
TI  - Percutaneous nephroscopic resection of pyelocaliceal transitional cell carcinoma
      in solitary kidney.
AB  - Percutaneous approaches to upper tract urothelial cancers have been performed in
      patients unsuitable for radical nephroureterectomy. We present two cases of
      transitional cell carcinoma involving the renal pelvis in either functional or
      anatomical solitary kidney, which were successfully treated by percutaneous
      nephroscopic resection using monopolar electrocautery. 

PMID- 24669136
TI  - Interposition flaps in vesicovaginal fistula repairs can optimize cure rate.

PMID- 24669137
TI  - Robot assisted laparoscopic retroperitoneal lymph node dissection in testicular
      tumor.

PMID- 24669135
TI  - Isolated ureteric endometriosis presenting as a ureteric tumor.
AB  - A 32 year old lady presented with recurrent left flank pain for 4 weeks and
      chronic lower back pain. CT without contrast showed no stones and mild left
      hydronephrosis. CT of the spine suggested an inflammatory process at L5-S1
      vertebra. The diagnosis was supported by a bone scan. Incidentally, the scan
      showed nonfunctioning left kidney. Diuretic renography confirmed poor perfusion
      and no excretion. A retrograde study showed narrowing of the ureter at the pelvic
      brim. Ureteroscopy showed a papillary mass in the lumen of the ureter from which
      multiple cold cup biopsies were taken. The pathology however was not conclusive.
      A robotic nephroureterectomy was carried out. Definitive pathology showed
      intrinsic endometriosis of the ureter. We conclude that endometriosis should be
      considered in the differential diagnosis of unexplained ureteric obstruction and
      ureteric lumen filling defects in young women. 

PMID- 24669138
TI  - Refractive surgery: the never-ending task of improving vision correction.

PMID- 24669139
TI  - Intrastromal corneal ring segments: how successful is the surgical treatment of
      keratoconus?
AB  - This review evaluates the outcomes of intrastromal corneal ring segment (ICRS)
      implantation for the treatment of keratoconus considering a new grading system
      based on the preoperative visual impairment of the patient. Additionally, a five
      year follow-up analysis of patients with stable and progressive keratoconus is
      performed in order to assess the long term stability of the surgical procedure.
      Corrected distance visual acuity decreased statistically significantly in
      patients with mild keratoconus (P < 0.01) but statistically significantly
      increased in all other grades (P < 0.05). The improvement in visual acuity and
      the decrease of keratometric and aberrometric values were stable throughout a
      long period of time in patients with stable keratoconus. In patients with
      progressive form keratoconus, a significant improvement was found immediately
      after the procedure, however clinically relevant regression greater than 3 D was
      observed at the end of the follow up period. 

PMID- 24669140
TI  - Current management of presbyopia.
AB  - Presbyopia is a physiologic inevitability that causes gradual loss of
      accommodation during the fifth decade of life. The correction of presbyopia and
      the restoration of accommodation are considered the final frontier of refractive
      surgery. Different approaches on the cornea, the crystalline lens and the sclera
      are being pursued to achieve surgical correction of this disability. There are
      however, a number of limitations and considerations that have prevented
      widespread acceptance of surgical correction for presbyopia. The quality of
      vision, optical and visual distortions, regression of effect, complications such
      as corneal ectasia and haze, anisometropia after monovision correction, impaired
      distance vision and the invasive nature of the currently techniques have limited
      the utilization of presbyopia surgery. The purpose of this paper is to provide an
      update of current procedures available for presbyopia correction and their
      limitations. 

PMID- 24669141
TI  - Refractive surgery in systemic and autoimmune disease.
AB  - Patients with underlying systemic disease represent challenging treatment dilemma
      to the refractive surgeon. The refractive error in this patient population is
      accompanied by a systemic disease that may have an ocular or even a corneal
      component. The literature is rather sparse about the use of laser refractive
      surgery (LRS) and such procedure is not approved by the United States Food and
      Drug Administration (FDA) in this patient population. Patients with collagen
      vascular disease, diabetes mellitus (DM), allergic and atopic disease, or human
      immunodeficiency virus (HIV) are never ideal for LRS. Patients with uncontrolled
      systemic disease or ocular involvement of the disease should not undergo LRS.
      However, a patient with well-controlled and mild disease, no ocular involvement,
      and not on multidrug regimen may be a suitable candidate if they meet stringent
      criteria. There is a need for a large, multicenter, controlled trial to address
      the safety and efficacy of LRS in patients with systemic disease before such
      technology can be widely adopted by the refractive surgery community. 

PMID- 24669142
TI  - Clear corneal incision in cataract surgery.
AB  - Since the introduction of sutureless clear corneal cataract incisions, the
      procedure has gained increasing popularity worldwide because it offers several
      advantages over the traditional sutured scleral tunnels and limbal incisions.
      Some of these benefits include lack of conjunctival trauma, less discomfort and
      bleeding, absence of suture-induced astigmatism, and faster visual
      rehabilitation. However, an increasing incidence of postoperative endophthalmitis
      after clear corneal cataract surgery has been reported. Different authors have
      shown a significant increase up to 15-fold in the incidence of endophthalmitis
      following clear corneal incision compared to scleral tunnels. The aim of this
      report is to review the advantages and disadvantages of clear corneal incisions
      in cataract surgery, emphasizing on wound construction recommendations based on
      published literature. 

PMID- 24669143
TI  - Gradient refractive index optics IOL: theoretical background and clinical
      results.
AB  - PURPOSE: To present the theoretical optical background and clinical results of a
      new multifocal intraocular lens (MIOL) concept-gradient refractive index optics
      (Gradiol). PATIENTS AND METHODS: Original mathematical modeling software was used
      to calculate optimal construction of the MIOL optic constructed from two polymer
      materials with different refractive indices. Gradiol lenses were manufactured
      from hydrophobic acrylic utilizing original step-by-step polymerization
      technology with the final power difference of of 3.5 D between optic components.
      Non-comparative prospective clinical study included 26 patients (29 eyes) who
      were candidates for MIOL implantation. All surgeries were performed at the S.
      Fyodorov Eye Microsurgery Complex State Institution, Moscow, Russia. After
      implantation of the Gradiol lenses, the postoperative evaluations included
      distance (best corrected visual acuity (BCVA)) and near visual acuity (NVA),
      contrast sensitivity (CS), and amplitude of pseudoaccommodation. Subjective
      patient's satisfaction was assessed using a questionnaire (VF-14). RESULTS: The
      mean age of the patients was 62.5 +/- 5.7 years (range 27-82 years). All surgical
      procedures were uneventful. At 6 months postoperatively, the mean uncorrected
      distance VA was 0.73 +/- 0.18, mean uncorrected near VA was 0.57 +/- 0.19, mean
      corrected distance VA was 0.89 +/- 0.15, mean corrected near VA was 0.84 +/-
      0.07, and amplitude of pseudoaccommodation was 4.75 +/- 0.5 D. Eighty-six percent
      of patients were spectacle independent for daily activities and reading. Optical
      disturbances that were functionally significant were reported by 10.7% of
      patients postoperatively. CONCLUSION: The clinical outcomes of this study
      confirmed the theoretical calculations of constructing MIOL optics from materials
      with different refractive indices.

PMID- 24669144
TI  - Pigmented hypopyon in association with Listeria monocytogenes endopthalmitis: an
      interesting case report following refractive surgery procedure with literature
      review.
AB  - PURPOSE: Listeria monocytogenes is an aerobic, motile, gram positive bacillus
      recognized as an intercellular pathogen in human where it most frequently affects
      neonates, pregnant women, elderly patients, and immunosuppressed individuals as
      well as healthy persons. Ocular listeriosis is rare, most frequently in the form
      of conjunctivitis, but has been also shown to cause rarely endophthalmitis with
      pigmented hypopyon and elevated intraocular pressure such as in our case.
      MATERIALS AND METHODS: We are reporting one immunocompetent patient presenting
      with dark hypopyon following laser refractive procedure. His clinical findings,
      investigations, and further management are all described with relevant literature
      review of similar cases. RESULTS: Diagnosis of ocular listeriosis was confirmed
      by positive culture of anterior chamber (AC) aspirate with identification of the
      above organism. His visual outcome was satisfactory with good preserved vision.
      CONCLUSION: We believe that his ocular infection was exogenous and that
      ophthalmologists should be aware of the causative organisms of colored hypopyon
      to avoid delayed diagnosis.

PMID- 24669145
TI  - Primary and secondary implantation of scleral-fixated posterior chamber
      intraocular lenses in adult patients.
AB  - PURPOSE: The purpose of this study is to evaluate and to compare the results of
      primary and secondary scleral-fixated posterior chamber intraocular lens (PCIOL)
      implantations in adult patients. MATERIALS AND METHODS: A retrospective analysis
      of scleral-fixated PCIOLs-implanted during (primary group) or after (secondary
      group) cataract surgery was performed. The median follow-up time of 96 patients
      was 6 months (minimum: 6; maximum: 35 months). Outcome measures were indications,
      corrected distance visual acuity (CDVA), change in visual acuity and
      complications. RESULTS: A total of 37 patients (38.5%) had primary implantations
      and 59 (61.5%) had secondary implantations. Penetrating keratoplasty was combined
      with secondary implantation in 13 cases. The median post-operative CDVA was 0.5
      in decimal notation in both groups (P = 0.576). The CDVA improved by at least one
      Snellen line or remained unchanged in 35 eyes (94.6%) in the primary group and in
      52 eyes (88.1%) in the secondary group (P = 0.263). Eyes with CDVA of 0.5 or
      higher were 62.2% (n = 23) in the primary group and 67.8% (n = 40) in the
      secondary group post-operatively (P = 0.066). The difference in early and late
      complications were not statistically significant between groups (P = 0.637, P =
      0.154, respectively). Regarding late complications, 30 eyes (81%) in the primary
      group and 40 eyes (67.9%) in the secondary group had no complications (P =
      0.154). CONCLUSION: Both primary and secondary scleral-fixated PCIOL
      implantations can provide favorable visual outcomes with lower complication
      rates. An important consideration is the appropriate timing for scleral fixation,
      taking into account the patient's characteristics and the course of the
      operation.

PMID- 24669146
TI  - Rose-K versus Soper contact lens in keratoconus: a randomized comparative trial.
AB  - PURPOSE: To perform a comparative evaluation of the efficacy and acceptability of
      Rose-K and Soper contact lenses in Keratoconus. SETTING: Dr. Rajendra Prasad
      Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New
      Delhi. MATERIALS AND METHODS: A randomized comparative clinical trial was
      performed in keratoconic eyes fitted with Rose-K (Rose-K group) and Soper (Soper
      group) contact lenses. Patients data were evaluated for best spectacle corrected
      visual acuity, best contact lens corrected visual acuity (BCLCVA), corneal
      topography, glare acuity, contrast sensitivity, tear function tests and specular
      microscopy. Patients were also asked to complete a self-reported comfort
      questionnaire at each visit. RESULTS: Sixty eyes were randomized to the Rose-K
      and Soper groups. The two groups were comparable in all the baseline parameters.
      There was a statistically significant improvement in BCLCVA in both groups at 3
      months (P < 0.01, both groups). The difference between in BCLCVA in both groups
      was not statistically significant. In both groups, there was a significant
      improvement in the comfort score at 3 months compared to baseline (P < 0.05, both
      group). The Rose-K group had statistically significantly better scores at 1 and 3
      months compared with the Soper group (P = 0.006 and P < 0.001 respectively). Both
      groups were associated with a significant (P < 0.01), but comparable improvement
      in glare acuity at 3 months. There was a significant improvement in contrast
      sensitivity at 3 months in both groups (P < 0.01); the Rose-K group was
      significantly better than the Soper group at 1 and 3 months (P = 0.001 and 0.002
      respectively). The mean number of trial lenses required for fitting Rose-K lens
      (2.00 +/- 0.59) was significantly lower than the Soper lens (3.43 +/- 0.82; P <
      0.001). CONCLUSION: Both the contact lens designs provide an equal improvement in
      visual acuity in patients with Keratoconus. However, Rose-K contact lens provides
      greater comfort, better quality of vision and requires less chair time compared
      with the Soper lens and hence may possibly have a greater acceptability.

PMID- 24669147
TI  - Comparison of morphological and functional endothelial cell changes after
      cataract surgery: phacoemulsification versus manual small-incision cataract
      surgery.
AB  - PURPOSE: To compare the morphological (cell density, coefficient of variation and
      standard deviation) and functional (central corneal thickness) endothelial
      changes after phacoemulsification versus manual small-incision cataract surgery
      (MSICS). DESIGN: Prospective randomized control study. MATERIALS AND METHODS: In
      this prospective randomized control study, patients were randomly allocated to
      undergo phacoemulsification (Group 1, n = 100) or MSICS (Group 2, n = 100) using
      a random number Table. The patients underwent complete ophthalmic evaluation and
      specular microscopy preoperatively and at 1and 6 weeks postoperatively.
      Functional and morphological endothelial evaluation was Noncon ROBO PACHY SP-9000
      specular microscope. Phacoemulsification was performed, the chop technique and
      MSICS, by the viscoexpression technique. RESULTS: The mean difference in central
      corneal thickness at baseline and 1 week between Group 1 and Group 2 was
      statistically significant (P = 0.027). However, this difference at baseline when
      compared to 6 week and 1 week, 6 weeks was not statistically significant (P >
      0.05). The difference in mean endothelial cell density between groups at 1 week
      and 6 weeks was statistically significant (P = 0.016). The mean coefficient of
      variation and mean standard deviation between groups were not statistically
      significant (P > 0.05, both comparisons). CONCLUSION: The central corneal
      thickness, coefficient of variation, and standard deviation were maintained in
      both groups indicating that the function and morphology of endothelial cells was
      not affected despite an initial reduction in endothelial cell number in MSICS.
      Thus, MSICS remains a safe option in the developing world.

PMID- 24669148
TI  - Prickly pear spine keratoconjunctivitis.
AB  - OBJECTIVES: To study the ocular and extra-ocular features, clinical presentation,
      and treatment of prickly pear glochids. MATERIALS AND METHODS: This retrospective
      study included 23 eyes of 21 patients with ocular prickly pear spines who were
      seen between August and October 2011 in the outpatient ophthalmic clinic at
      Prince Rashid Bin Al Hassan military hospital in Jordan. Medical records of
      patients including age, gender, history of exposure to prickly pear plants, and
      ocular examination were reviewed. All glochids were localized and removed with
      forceps under topical anesthesia with the patient at the slit lamp. Patients were
      followed up after one week. RESULTS: The mean age of patients was 37.1 years with
      a male to female ratio of 1.6: 1. Involvement of the right eye was seen in 61.9%
      patients, left eye in 28.6% patients, and bilateral involvement in 9.5% patients.
      Glochids were most commonly found in the upper subtarsal conjunctival space
      (47.6%) followed by inferior palpebral conjunctiva in 23.8% eyes. The most common
      complaint was eye irritation in 95.2% patients. Pain was a complaint in 57.1%
      patients. Superior corneal epithelial erosions or ulcer were found in 33.3%
      patients, inferior corneal epithelial erosions in 19.1% patients, and diffuse
      epithelial erosions in 9.5% patients. Glochids were found in other parts of the
      body in 38.1% patients. CONCLUSION: Although prickly pear glochid ocular surface
      injury is not uncommon in the region during summer, it should be considered in
      patient with eye pain during that period. Farmers who are in close contact with
      prickly pears should use protective eyeglasses and gloves.

PMID- 24669149
TI  - Modulatory effect of different riboflavin compositions on the central corneal
      thickness of African keratoconus corneas during collagen crosslinking.
AB  - PURPOSE: A pilot investigation to transfer the established corneal collagen
      crosslinking (CXL) procedure in European eyes into clinically affected African
      eyes and to optimize the treatment by adapting the riboflavin composition.
      MATERIALS AND METHODS: CXL was performed in 15 eyes (11 patients) with advanced
      stages of keratoconus in the Eye Clinic of Bafoussam in the West Region of
      Cameroon. The following six riboflavin compositions with different portions of
      active swelling additives were applied: Solution 1 (0.5%
      methylhydroxypropylcellulose [MHPC]), solution 2 (1.0% MHPC), solution 3 (1.7%
      MHPC), solution 4 (5% dextran), solution 5 (10% dextran) and solution 6 (no
      active swelling ingredient). The central corneal thickness (CCT) was measured by
      ultrasound pachymetry before and after de-epithelialization and at least every 10
      min during CXL. RESULTS: THE APPLICATION OF THE RIBOFLAVIN SOLUTIONS RESULTED IN
      THE FOLLOWING MEAN FINAL CCT VALUES: 172 +/- 15% using solution 1 (60 min/n = 5);
      183 +/- 8% using solution 2 (60 min/n = 5); 170% using solution 3 (60 min/n = 1);
      80% using solution 4 (45 min/n = 1); 99% using solution 5 (45 min/n = 1) and 150
      +/- 13% using solution 6 (50 min/n = 2). CONCLUSIONS: The combination of
      riboflavin compositions with swelling and stabilizing effects on the corneal
      stroma seems necessary in African eyes with advanced keratoconus. Further studies
      are required to confirm these primary results.

PMID- 24669150
TI  - Corneal topography patterns in the Tehran eye study: warning about the high
      prevalence of patterns with a skewed radial axis.
AB  - PURPOSE: The purpose of this study is to determine the distribution of corneal
      topography patterns in Tehran. MATERIALS AND METHODS: In this population-based
      study, a total of 442 individuals were randomly selected by cluster sampling for
      complete ophthalmologic examination. A total of 404 (788 eyes) met the inclusion
      criteria and were enrolled in this study. Orbscan II (Bausch and Lomb Surgical,
      Salt Lake City, USA) was used to determine the anterior segment indices and axial
      power maps for each eye. RESULTS: On the basis of the axial power maps, the
      symmetric bowtie (SB) (29.0%) and asymmetric bowtie with inferior steepening
      (16.7%) patterns were the most prevalent and the irregular (3.3%) and superior
      steepening (1.5%) patterns the least prevalent. Asymmetric bowtie pattern with a
      skewed radial axis (AB-SRAX) was seen in 7.6% of eyes. These cases had both
      thinner and steeper corneas compared with round and SB ones (P < 0.014 and P <
      0.006). Maximum anterior elevation in 5 mm zone, of AB-SRAX corneas were higher
      than other patterns (P < 0.01) except for superior steepened and inferior
      steepened ones. CONCLUSIONS: The distribution of corneal topographic patterns in
      Iranians seems like other Asian population on the whole. The 7.6% prevalence of
      AB-SRAX patterns may be a warning on keratoconus prevalence in our population.
      This is in line with recent regional reports.

PMID- 24669152
TI  - Severe bilateral paralimbal sterile infiltrates after photorefractive
      keratectomy.
AB  - This study presents a case report of the clinical presentation and management of
      a 47-year-old male myope who underwent photorefractive keratectomy (PRK) and
      developed bilateral sterile corneal infiltrates at 1 day post-operatively. The
      patient was successfully treated with aggressive topical antibiotic and topical
      steroid therapy. The final corrected distance visual acuity (CDVA) was 20/25 with
      faint corneal scarring. Peripheral sterile corneal infiltrate can occur after PRK
      with excellent prognosis. Infectious causes should be suspected in all cases of
      corneal infiltrate. The most likely cause of peripheral sterile corneal
      infiltrate in this case was pooling of the tear film containing antigens under
      the bandage contact lens. 

PMID- 24669151
TI  - Manual suture less small incision cataract surgery in patients with uveitic
      cataract.
AB  - PURPOSE: The purpose of this study is to evaluate the outcome of manual small
      incision cataract surgery (SICS) in eyes with uveitic cataract. SETTING: Medical
      college hospital of the subcontinent. DESIGN: Retrospective case series.
      MATERIALS AND METHODS: In this retrospective study, patients who underwent SICS
      with posterior chamber intraocular lens implantation for uveitic cataract from
      2006 to 2009 were evaluated. Patients with less than 3 months follow-up were
      excluded. Post-operative vision and complications were analyzed. RESULTS: A total
      of 54 patients completed the study. The mean age was 52.3 +/- 9.3 years. The mean
      follow-up was 11.53 +/- 5.05 months. The mean surgical time was (10.2 +/- 3.8
      min). Etiological diagnosis was possible in 31.41% (17/54) of patients. There was
      a statistically significant improvement in vision after surgery (P < 0.001). When
      uveitis was well-controlled, pre-operative corticosteroids did not change post
      operative inflammation (P = 0.796). However, pre-operative corticosteroids were
      statistically significantly associated to final best corrected visual acuity
      (BCVA) (P = 0.010). CONCLUSION: SICS with posterior chamber intraocular lens
      implantation is safe in most cataracts due to uveitis and improves BCVA at 6
      months. Inflammation should be well-controlled pre-operatively for at least 3
      months. Posterior capsule opacification, macular edema and persistent uveitis
      were the main factors affecting visual outcome. SICS requires minimal
      instrumentation, surgical time is short and can also be performed in rural
      clinics and eye-camps, where phacoemulsification machines are unavailable. SICS
      may be a more practical and cost-effective technique for uveitic cataract, in
      such circumstances.

PMID- 24669153
TI  - Intraoperative fracture of phacoemulsification tip.
AB  - Phacoemulsification (phaco) is an established procedure for cataract extraction
      and has undergone a significant advances in techniques, machines and phaco tips.
      The Aspiration Bypass System (ABS) phaco tip was introduced for
      phacoemulsification in 1998. The ABS tip allows fluid to be drawn through the
      opening when the phaco tip is occluded by nuclear material. The ABS tip allowed
      the safe use of high vacuum and flow rates and improved chamber stability by
      decreasing surge and therefore reducing intraoperative complications. To date, no
      disadvantages of ABS tips have been reported. We report a unique case of an
      intraoperative break of an ABS phaco tip during routine cataract surgery. 

PMID- 24669154
TI  - Repositioning of pedicle conjunctival flap performed for refractory corneal
      ulcer.
AB  - A 50-year-old male was referred with a previous history of conjunctival flap (CF)
      for a nonhealing fungal corneal ulcer with extreme corneal thinning in the right
      eye. The peritomy for the CF extended from 6:30 to 9:30 clock h on the cornea.
      The CF was disengaged, peritomy area deepithelialized, and CF was repositioned.
      He later underwent penetrating keratoplasty and achieved 20/40 best corrected
      visual acuity. The authors present a new concept for surgically repositioning CF
      s to the original site immediately after healing of the corneal ulcer. 

PMID- 24669155
TI  - Alternaria keratitis after deep anterior lamellar keratoplasty.
AB  - To describe a case of Alternaria keratitis in a 30-year-old male patient who
      presented with bilateral vascularised central corneal opacity and underwent deep
      anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for
      recurrent epithelial defect with a bandage contact lens in the follow-up visits
      after DALK. Subsequently, patient presented with pigmented fungal keratitis,
      which on culture examination of the corneal scrapping demonstrated Alternaria
      species. Patient had to undergo a repeat DALK as the keratitis did not resolve
      with medical therapy alone. Patient did not have a recurrence for 11 months
      following the regraft. This case report highlights the importance of considering
      the Alternaria species as a possibile cause of non-resolving fungal keratitis
      after DALK. 

PMID- 24669156
TI  - Alopecia following oral acyclovir for the treatment of herpes simplex keratitis.
AB  - The authors report acyclovir-induced alopecia in a patient treated for herpetic
      keratouveitis. A 32-years-old female was diagnosed with herpetic keratouveitis.
      She was placed on prednisolone acetate (1%) suspension four times a day, atropine
      sulfate (1%) thrice a day, and oral acyclovir 400 mg twice-daily. Three weeks
      following oral acylovir, keratouveitis improved, but she developed alopecia
      without any drug eruptions. Oral acyclovir was discontinued. Three months later,
      alopecia completely resolved. Alopecia may be considered a possible complication
      following oral acyclovir. 

PMID- 24669157
TI  - Look beyond cancer for quality of life.

PMID- 24669158
TI  - Dendritic cell based immunotherapy of cancer with cell penetrating domains.

PMID- 24669159
TI  - The effect of local therapy on breast cancer mortality: is there an age
      interaction?
AB  - There are no randomized trials comparing local therapy versus no therapy in
      patients with primary breast cancer, as such trials would be deemed unethical.
      Thus, the impact of local therapy on breast cancer mortality is poorly
      understood. However, an overview of clinical trials comparing various
      permutations in the local therapy of breast cancer suggests that inadequate local
      therapy increases the risk of local recurrences, and thereby increases breast
      cancer mortality. Yet, age-interactions are commonly reported in studies that
      have examined the etiology, prognosis, and treatment of breast cancer, and might
      be associated with the effect of local therapy as well. Moreover, the effect of
      local therapy on breast cancer mortality might be time-dependent. In cohorts of
      women with high-risk tumors (predominantly younger women) local therapy may
      adversely (but only transiently) perturb the natural history of breast cancer. In
      contrast, such an effect is not evident in cohorts of women with low-risk tumors
      (predominantly older women). For both groups of patients, local therapy appears
      to ultimately have a beneficial effect in reducing breast cancer mortality, but
      in patients with low-risk tumors the benefit is immediate, while in patients with
      high-risk tumors it is delayed. Evidence for such an age-interaction is derived
      from comparison of the breast cancer hazard curves in women with high-risk and
      low-risk tumors, and analysis of the mammography screening trials. Neo-adjuvant
      systemic therapy may eventually prove useful in modulating the effects of local
      therapy. 

PMID- 24669160
TI  - 18 FDG PET-CT and Unknown Primary Tumours.

PMID- 24669161
TI  - Nephron sparing surgery for unilateral non-syndromic wilms tumor.
AB  - The initial therapy for most children with Wilms tumor is radical nephrectomy.
      Several centers, have explored the role of Nephron-sparing procedures in children
      with unilateral non-syndromic Wilms tumors. The primary motivation for this
      approach is concern about late occurrence of renal dysfunction after unilateral
      nephrectomy. We report our experience with NSS for unilateral non-syndromic Wilms
      tumor. We reviewed the records of nine children who underwent nephron sparing
      surgery for unilateral, nonsyndromic Wilms tumors at our Hospital between Jan
      2000 through Jan 2012. All patients received preoperative chemotherapy with two
      drugs (vincristine, and dactinomycin) following which patients underwent tumor
      resection. Subsequent renal function was assessed by estimating the glomerular
      filtration rate using creatinine clearance and other measures of long-term renal
      function assessment included blood pressure evaluation and the need for
      antihypertensive medications. During the study period nine children with a mean
      age 19.66 +/- 14.37 months at diagnosis and presenting with unilateral non
      syndromic Wilms tumor underwent nephron sparing surgery. In all the nine
      children, the renal plane of resection showed a tumor-free margin. Post-operative
      serum creatinine repeated at the end of 3 months revealed maintenance of good
      renal function in all children. Nephron sparing surgery is a safe and effective
      option in the management of early stage unilateral non-syndromic Wilms tumor. It
      is oncologically safe and does not lead to decreased local tumor control. The
      function of the kidney remnant remains rather well. 

PMID- 24669164
TI  - Malignant proliferating trichilemmal tumor in young male.

PMID- 24669163
TI  - Portal vein embolization and ligation for extended hepatectomy.
AB  - Portal vein occlusion through embolization or ligation (PVE, PVL) offers the
      possibility of increasing the future liver remnant (FLR) and thus reducing the
      risk of hepatic failure after extended hepatectomy We reviewed the indications,
      scope and applicability of PVE/PVL in treatment of primary and secondary liver
      tumours. A thorough PubMED, Embase, Ovid and Cochrane database search was carried
      out for all original articles with 30 patients or more undergoing either PVE and
      any patient series with PVL, irrespective of number with outcome measure in at
      least one of the following parameters: FLR volume change, complications, length
      of stay, time to surgery, proportion resectable and survival data. PVE can be
      performed with a technical success in 98.9 % (95 % confidence interval 97-100)
      patients, with a mean morbidity of 3.13 % (95 % CI 1.21-5.04) and a median in
      hospital stay of 2.1 (range 1-4) days (very few papers had data on length of stay
      following PVE). The mean increase in volume of the FLR following PVE was 39.75 %
      (95 % CI 30.8-48.6) facilitating extended liver resection after a mean of 37.13
      days (95 % CI 28.51-45.74) with a resectability rate of 76.88 % (95 % CI 70.91
      82.84). Morbidity and mortality following such extended liver resections after
      PVE is 26.58 % (95 % CI 19.20-33.95) and 2.59 % (95 % CI 1.34-3.83) respectively
      with an in-patient stay of 13.57 days (95 % CI 9.8-17.37). However following post
      PVE liver hypertrophy 6.29 % (95 % CI 2.24-10.34) patients still have post
      resection liver failure and up to 14.2 % (95 % CI -8.7 to 37) may have positive
      resection margins. Up to 4.80 % (95 % CI 2.07-7.52) have failure of hypertrophy
      after PVE and 17.46 % (95 % CI 11.89-23.02) may have disease progression during
      the interim awaiting hypertrophy and subsequent resection. PVL has a greater
      morbidity and duration of stay of 5.72 % (95 % CI 0-15.28) and 10.16 days (95 %
      CI 6.63-13.69) respectively; as compared to PVE. Duration to surgery following
      PVL was greater at 53.6 days (95 % CI 32.14-75.05). PVL induced FLR hypertrophy
      by a mean of 64.65 % (95 % CI 0-136.12) giving a resectability rate of 63.68 %
      (95 % CI 56.82-70.54). PVL failed to produce enough liver hypertrophy in 7.4 % of
      patients (95 % CI 0-16.12). Progression of disease following PVL was 29.29 (95%CI
      15.69-42.88). PVE facilitates an extended hepatectomy in patients with limited or
      inadequate FLR, with good short and long-term outcomes. Patients need to be
      adequately counselled and consented for PVE and EH in light of these data. PVL
      would promote hypertrophy as well, but clearly PVE has advantages as compared to
      PVL on account of its inherent "minimally invasive" nature, fewer complications,
      length of stay and its feasibility to have shorter times to surgery. 

PMID- 24669162
TI  - Strategies for fertility preservation in young patients with cancer: a
      comprehensive approach.
AB  - As a result of treatment innovations, the survival rates of young people with
      cancer have increased substantially. The cancers most frequently diagnosed in
      adults aged 25-49 years include breast, colorectal and cervical cancer and
      malignant melanoma (Cancer Research UK, 2009). The 5-year survival rates of over
      90 % for many malignancies are now reported in young people. But the diagnosis
      and treatment of cancer often poses a threat to fertility. Methods of fertility
      preservation are evolving quickly and awareness needs to grow in the medical
      community regarding these methods. Studies suggest that the ability to have
      biological children is of great importance to many people. The possible future
      effects of chemotherapy or radiotherapy on fertility should be discussed with all
      cancer patients who have reproductive potential. Moreover, fertility preservation
      should be considered for all young people undergoing potentially gonadotoxic
      treatment. This article covers the various methods of fertility preserving
      options in young men and women with respect to the various treatment modalities
      that they may be subjected to. Sperm banking is a simple and low cost
      intervention. Embryo cryopreservation is the only established method of female
      fertility preservation. Oocyte cryopreservation offers a useful option for women
      without a male partner. Emergency ovarian stimulation and cryopreservation of
      ovarian tissue (followed by tissue transplantation or in-vitro maturation of
      oocytes) are experimental techniques for women who require urgent cancer
      treatment. Large, well-controlled studies are also required to identify any
      unexpected long-term sequelae of cryopreservation of oocytes and ovarian tissue. 

PMID- 24669165
TI  - Special Relevance of FDG-PET as an Upfront Diagnostic Modality at Initial
      Diagnosis and in Suspected Recurrence in Patients of Breast Carcinoma Hailing
      From Lower Socioeconomic Status Owing to Relative Late Presentation: A Pilot
      Study in a Medical College Hospital Setting in India.
AB  - FDG-PET has found relatively limited use in routine management of breast
      carcinoma due to its limited utility in assessing the primary and axillary lymph
      node status. The aim of the study was to assess its role in a medical school and
      municipal hospital setting of Mumbai, where majority belongs to the lower
      socioeconomic status and presents relatively late and hence whole body FDG-PET
      could find important place for assessing whole body disease status that would
      justify being used upfront in this group of patients. Thus, the premise of this
      study was that FDG-PET will have special relevance in this particular setting for
      evaluation of patients of breast carcinoma with respect to initial staging,
      detection of locoregional recurrence and metastasis and assessing response to
      systemic treatment. A total of 52 patients proven to have breast carcinoma, who
      had undergone (18)F FDG-PET for disease staging at initial diagnosis and in in
      recurrent disease staging with a few cases as a baseline study for early
      treatment monitoring purposes over a study period of 3 years, were included in
      this analysis. 33.3 % of patients with pretreatment baseline FDG-PET were
      upstaged with diagnosis of additional lesions in the adrenal gland, liver,
      internal mammary, cervical lymph nodes and the mediastinum. On a lesion specific
      analysis, the percentage of increased lesion detection (including both lymph node
      with distant metastasis) by FDG-PET was 42.7 %. FDG-PET was found to be 100 %
      sensitive and specific for confirming recurrent breast cancer. Four out of 18
      patients on chemotherapy underwent second FDG-PET after first cycle of
      chemotherapy, showed responsiveness to chemotherapy by decreased maximum
      standardized uptake value (SUVmax). FDG-PET showed 9 liver lesions in 6 patients,
      only 3 of them was reported in USG. In one patient USG abdomen was inconclusive
      between hemangioma and metastasis, FDG-PET ruled out liver metastasis in this
      patient. In the examined patient population belonging to lower socioeconomic
      status, where usual presentation is relatively late, upfront whole body survey
      with FDG-PET or PET/CT is of considerable value in view of higher probability of
      existence of metastatic disease, thus can be an important one-stop shop tool in
      assessing whole body disease status in a single examination. It also proved
      efficacious in diagnosing loco regional and distant recurrence, metabolic
      characterization of lump and early response to treatment in the examined few
      cases following one cycle of chemotherapy in locally advanced breast cancer. 

PMID- 24669167
TI  - Primary gastric inflammatory myofibroblastic tumor in an adult-case report with
      brief review.
AB  - The term inflammatory myofibroblastic tumor more commonly referred to as
      "pseudostumor ", denotes a pseudosarcomatous inflammatory lesion that contains
      spindle cells, myofibroblasts, plasma cells, lymphocytes and histiocytes. It
      exhibits a variable biological behavior that ranges from frequently benign
      lesions to more aggressive variants. Inflammatory myofibroblastic tumor (IMT) of
      the stomach is extremely rare and its prognosis is unpredictable. We present a 45
      year-old diabetic man with a gastric Inflammatory myofibroblastic tumor. The
      histopathological and immunohistochemical analysis was the key to reach
      diagnosis. 

PMID- 24669166
TI  - Role of Cyclooxygenase 2 (COX-2) in Prognosis of Breast Cancer.
AB  - COX-2 regulates tumour growth, invasion and metastasis in breast cancer. This
      study investigated the association between COX-2 expression in human breast
      cancer versus the expression of ER, PR, HER-2/neu, as well as its association
      with other established prognostic indicators like age, menopausal status, tumour
      size, lymph nodal status, stage, grade, NPI and histological subtype, and aims to
      validate the role of overexpression of COX-2 as a prognostic marker in patients
      with breast cancer in Indian subcontinent. In this hospital based study of 123
      breast cancer patients (Group-A) and 76 female patients with benign breast
      disease (Group-B) attending a Comprehensive Breast Clinic at a reputed institute
      in Eastern India, COX-2 protein expression was measured from breast tissue using
      the Western Blot Technique. COX-2 mRNA expression was measured by RT-PCR
      Technique. ER, PR and HER-2/neu status was measured by immunohistochemistry
      methods. COX-2 was not expressed in the control group. The proportion of COX-2
      positive tumours was significantly higher in patients of age >50 years [52(91.2
      %), p < 0.01], postmenopausal status [64(90.1 %), p < 0.01], advanced stage of
      disease (p < 0.01), higher grade (p < 0.01), larger tumors (p < 0.01), metastatic
      lymph nodes (p < 0.01) and NPI >= 5.4 (p < 0.01). COX-2 expression was seen in ER
      negative [66(95.7 %), p < 0.01], PR-negative [76(92.7 %), p < 0.01], and HER
      2/neu positive tumours [29(100.0 %), p < 0.01]. Risk of COX-2 positivity was
      found to be 2.74 times more for postmenopausal status, 6.90 times more for large
      size tumours (>= 2.5), 34.37 times more for node positive tumours, 9.26 times
      more with ER negative patients and 5.88 times more for PR negative patients. COX
      2 expression is associated with established indicators of poor prognosis such as
      postmenopausal status, age >50 year, advanced stage of disease, large tumour
      size, higher grade, lymph node metastasis, NPI >= 5.4, ER negativity, PR
      negativity and HER-2/neu positivity. Thus, COX-2 expression implies aggressive
      tumour biology, and may play an important role as a prognostic marker. 

PMID- 24669168
TI  - Malignant granular cell tumor of the tongue: a clinico-pathological challenge.

PMID- 24669169
TI  - Synovial sarcoma oropharynx - a case report and review of literature.

PMID- 24669170
TI  - Multicentric Jejunal and Omental GIST with an Unusual Clinical Presentation-A
      Case Report.

PMID- 24669171
TI  - Ewing's Sarcoma of Mandible: A Very Rare Disease and Review of Indian Literature.

PMID- 24669172
TI  - Malignant adnexal tumour-eccrine hidradeno carcinoma a case report.

PMID- 24669173
TI  - Primitive neuroectodermal tumour of breast-a case report.

PMID- 24669174
TI  - Avoiding patient harm from a magnesium bolus dose.
AB  - How to avoid patient harm from a magnesium bolus dose. 

PMID- 24669175
TI  - Hospitals have an extra year to meet stage 2 meaningful use standards: american
      hospital association wants new concessions.
AB  - Hospitals gain a year to meet stage 2 meaningful use rules. 

PMID- 24669176
TI  - New medical devices.
AB  - FDA approvals, drug indications, and updates. FDA approvals, drug indications,
      and updates.

PMID- 24669177
TI  - Pharmaceutical approval update.
AB  - Simeprevir (Olysio) for chronic hepatitis C infection; coagulation Factor XIII A
      subunit (recombinant) (Tretten) for bleeding prevention in congenital Factor XIII
      A-subunit deficiency; and umeclidinium and vilanterol inhalation powder (Anoro
      Ellipta) for chronic obstructive pulmonary disease. 

PMID- 24669178
TI  - Mipomersen (kynamro): a novel antisense oligonucleotide inhibitor for the
      management of homozygous familial hypercholesterolemia.
AB  - Mipomersen (Kynamro) for homozygous familial hypercholesterolemia. 

PMID- 24669179
TI  - Specialty pharmacy networks for hospitals in the offing: absence of onsite access
      to specialty pharmaceuticals has care and financial implications.
AB  - Two competing hospital networks are assembling specialty pharmacy programs to
      satisfy drug manufacturers' requirements for delivery of costly, restricted
      distribution drugs to hospitals. Hospitals' inability to dispense such drugs can
      affect patient care and revenue. 

PMID- 24669180
TI  - Implications of recent controlled substance policy initiatives.
AB  - Legislative and regulatory efforts to address controlled substance diversion and
      overuse of narcotics are affecting prescription drug utilization and patient
      care. These initiatives can influence formulary drug selection, prior
      authorization procedures, and drug utilization strategies. 

PMID- 24669182
TI  - American society of hematology: 55th annual meeting and exposition.

PMID- 24669181
TI  - Drugs that offer a survival advantage for men with bone metastases resulting from
      castration-resistant prostate cancer: new and emerging treatment options.
AB  - A survival benefit has been demonstrated or is under investigation as the primary
      outcome among certain recently approved agents and investigational agents for men
      with metastatic castration-resistant prostate cancer that has spread to bone. 

PMID- 24669183
TI  - Suitability of Organic Matter Surrogates to Predict Trihalomethane Formation in
      Drinking Water Sources.
AB  - Broadly applicable disinfection by-product (DBP) precursor surrogate parameters
      could be leveraged at drinking water treatment plants (DWTPs) to curb formation
      of regulated DBPs, such as trihalomethanes (THMs). In this study, dissolved
      organic carbon (DOC), ultraviolet absorbance at 254 nm (UV254), fluorescence
      excitation/emission wavelength pairs (IEx/Em), and the maximum fluorescence
      intensities (FMAX) of components from parallel factor (PARAFAC) analysis were
      evaluated as total THM formation potential (TTHMFP) precursor surrogate
      parameters. A diverse set of source waters from eleven DWTPs located within
      watersheds underlain by six different soil orders were coagulated with alum at pH
      6, 7, and 8, resulting in 44 sample waters. DOC, UV254, IEx/Em, and FMAX values
      were measured to characterize dissolved organic matter in raw and treated waters
      and THMs were quantified following formation potential tests with free chlorine.
      For the 44 sample waters, the linear TTHMFP correlation with UV254 was stronger
      (r2=0.89) than I240/562 (r2=0.81, the strongest surrogate parameter from
      excitation/emission matrix pair picking), FMAX from a humic/fulvic acid-like
      PARAFAC component (r2=0.78), and DOC (r2=0.75). Results indicate that UV254 was
      the most accurate TTHMFP precursor surrogate parameter assessed for a diverse
      group of raw and alum-coagulated waters.

PMID- 24669184
TI  - Removal of TiO2 Nanoparticles During Primary Water Treatment: Role of Coagulant
      Type, Dose, and Nanoparticle Concentration.
AB  - Nanomaterials from consumer products (i.e., paints, sunscreens, toothpastes, and
      food grade titanium dioxide [TiO2]) have the capacity to end up in groundwater
      and surface water, which is of concern because the effectiveness of removing them
      via traditional treatment is uncertain. Although aggregation and transport of
      nanomaterials have been investigated, studies on their removal from suspension
      are limited. Hence, this study involves the development of scaled-down jar tests
      to determine the mechanisms involved in the removal of a model metal oxide
      nanoparticle (NP), TiO2, in artificial groundwater (AGW), and artificial surface
      water (ASW) at the primary stages of treatment: coagulation, flocculation, and
      sedimentation. Total removal was quantified at the end of each treatment stage by
      spectroscopy. Three different coagulants-iron chloride (FeCl3), iron sulfate
      (FeSO4), and alum [Al2(SO4)3]-destabilized the TiO2 NPs in both source waters.
      Overall, greater than one-log removal was seen in groundwater for all coagulants
      at a constant dose of 50 mg/L and across the range of particle concentrations
      (10, 25, 50, and 100 mg/L). In surface water, greater than 90% removal was seen
      with FeSO4 and Al2(SO4)3, but less than 60% when using FeCl3. Additionally,
      removal was most effective at higher NP concentrations (50 and 100 mg/L) in AGW
      when compared with ASW. Zeta potential was measured and compared between AGW and
      ASW with the presence of all three coagulants at the same treatment stage times
      as in the removal studies. These electrokinetic trends confirm that the greatest
      total removal of NPs occurred when the magnitude of charge was smallest (<10 mV)
      and conversely, higher zeta potential values (>35 mV) measured were under
      conditions with poor removal (<90%). These results are anticipated to be of
      considerable interest to practitioners for the assessment of traditional
      treatment processes' capacity to remove nanomaterials prior to subsequent
      filtration and distribution to domestic water supplies.

PMID- 24669185
TI  - Targeted therapy for sarcomas.
AB  - Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human
      cancers. They may arise as primary tumors in either bone or soft tissue, with
      approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year
      in the United States. There are at least 50 different subtypes of soft tissue
      sarcoma, with new ones described with ever-increasing frequency. One way to look
      at sarcomas is to divide them into categories on the basis of their genetic make
      up. One group of sarcomas has an identifiable, relatively simple genetic
      signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22
      translocation seen in Ewing's sarcoma. These specific abnormalities often lead to
      the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are
      helpful as diagnostic tools and may become therapeutic targets in the future.
      Another group of sarcomas is characterized by complex genetic abnormalities as
      seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is
      important to keep these distinctions in mind when contemplating the development
      of targeted agents for sarcomas. Different abnormalities in sarcoma could be
      divided by tumor subtype or by the molecular or pathway abnormality. However,
      some existing drugs or drugs in development may interfere with or alter more than
      one of the presented pathways. 

PMID- 24669186
TI  - Genistein suppresses tumor necrosis factor alpha-induced inflammation via
      modulating reactive oxygen species/Akt/nuclear factor kappaB and adenosine
      monophosphate-activated protein kinase signal pathways in human synoviocyte MH7A
      cells.
AB  - AIMS: Genistein, an isoflavone derivative found in soy, is known as a promising
      treatment for rheumatoid arthritis (RA). However, the detailed molecular
      mechanism of genistein in suppression of proinflammatory cytokine production
      remains ambiguous. The aim of this work was to evaluate the signal pathway by
      which genistein modulates inflammatory cytokine expression. MATERIALS AND
      METHODS: MH7A cells were stimulated with tumor necrosis factor (TNF)-alpha and
      incubated with genistein, and interleukin (IL)-1beta, IL-6, and IL-8 production
      was measured by enzyme-linked immunosorbent assay. Nuclear translocation of
      nuclear factor (NF)-kappaB was measured by a confocal fluorescence microscopy.
      The intracellular accumulation of reactive oxygen species (ROS) was monitored
      using the fluorescent probe 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein
      diacetate. Signal-transduction protein expression was measured by Western blot.
      RESULTS: Genistein decreased the secretion of IL-1beta, IL-6, and IL-8 from TNF
      alpha-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF
      alpha-induced NF-kappaB translocation as well as phosphorylation of IkappaB
      kinase-alpha/beta and IkappaBalpha, and also suppressed TNF-alpha-induced AMPK
      inhibition. The production of IL-1beta, IL-6, and IL-8 induced by TNF-alpha was
      decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting
      that inhibition of Akt activation might inhibit IL-1beta, IL-6, and IL-8
      production induced by TNF-alpha. In addition, we also found that pretreatment
      with the adenosine monophosphate-activated protein kinase (AMPK) agonist 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside obviously inhibited TNF
      alpha-induced proinflammatory cytokine production. These observations suggest
      that the inhibitory effect of genistein on TNF-alpha-induced proinflammatory
      cytokine production is dependent on AMPK activation. CONCLUSION: These findings
      indicate that genistein suppressed TNF-alpha-induced inflammation by inhibiting
      the ROS/Akt/NF-kappaB pathway and promoting AMPK activation in MH7A cells.

PMID- 24669187
TI  - Medical device design for adolescent adherence and developmental goals: a case
      study of a cystic fibrosis physiotherapy device.
AB  - PURPOSE: This study investigates the psychosocial aspects of adolescent medical
      device use and the impact on adolescent adherence and goals for the transitional
      years between child and adulthood. PATIENTS AND METHODS: Interviews were carried
      out with 20 adolescents with cystic fibrosis, investigating adolescent medical
      device use and experiences in relation to their personal and social lives and
      development through the adolescent years. The qualitative dataset was
      thematically examined using a content analysis method. RESULTS: The results show
      that adolescent users of medical technologies want their independence and
      capabilities to be respected. Adolescent adherence to medical device use was
      associated with short- and long-term motivations, where older adolescents were
      able to comprehend the longer-term benefits of use against short-term
      inconvenience more acutely than younger adolescents. It was suggested that
      medical devices could provide a tool for communication with families and
      clinicians and could support adolescents as they take responsibility for managing
      their condition. Themes of "fitting into teenage life" and "use in the community"
      were associated with adolescents' needs to form their own identity and have
      autonomy. CONCLUSION: This study shows that adolescent needs regarding medical
      device use are complex. It provides evidence to suggest that devices designed
      inclusively for adolescents may lead to improved adherence and also facilitate
      transition through the adolescent years and achievement of adolescent goals.

PMID- 24669188
TI  - Usability testing of a monitoring and feedback tool to stimulate physical
      activity.
AB  - INTRODUCTION: A MONITORING AND FEEDBACK TOOL TO STIMULATE PHYSICAL ACTIVITY,
      CONSISTING OF AN ACTIVITY SENSOR, SMARTPHONE APPLICATION (APP), AND WEBSITE FOR
      PATIENTS AND THEIR PRACTICE NURSES, HAS BEEN DEVELOPED: the 'It's LiFe!' tool. In
      this study the usability of the tool was evaluated by technology experts and end
      users (people with chronic obstructive pulmonary disease or type 2 diabetes, with
      ages from 40-70 years), to improve the user interfaces and content of the tool.
      PATIENTS AND METHODS: THE STUDY HAD FOUR PHASES: 1) a heuristic evaluation with
      six technology experts; 2) a usability test in a laboratory by five patients; 3)
      a pilot in real life wherein 20 patients used the tool for 3 months; and 4) a
      final lab test by five patients. In both lab tests (phases 2 and 4) qualitative
      data were collected through a thinking-aloud procedure and video recordings, and
      quantitative data through questions about task complexity, text
      comprehensiveness, and readability. In addition, the post-study system usability
      questionnaire (PSSUQ) was completed for the app and the website. In the pilot
      test (phase 3), all patients were interviewed three times and the Software
      Usability Measurement Inventory (SUMI) was completed. RESULTS: After each phase,
      improvements were made, mainly to the layout and text. The main improvement was a
      refresh button for active data synchronization between activity sensor, app, and
      server, implemented after connectivity problems in the pilot test. The mean score
      on the PSSUQ for the website improved from 5.6 (standard deviation [SD] 1.3) to
      6.5 (SD 0.5), and for the app from 5.4 (SD 1.5) to 6.2 (SD 1.1). Satisfaction in
      the pilot was not very high according to the SUMI. DISCUSSION: The use of
      laboratory versus real-life tests and expert-based versus user-based tests
      revealed a wide range of usability issues. The usability of the It's LiFe! tool
      improved considerably during the study.

PMID- 24669189
TI  - Health-related quality of life, anxiety, and depressive symptoms in children with
      primary immunodeficiencies.
AB  - INTRODUCTION: The aims of this study were to evaluate levels of health-related
      quality of life (HRQOL) and the presence of anxiety and depressive symptoms in
      children with primary immunodeficiency disease (PID) in Serbia. MATERIALS AND
      METHODS: Self- and parent-rated data from 25 children with PID were available. As
      controls, data from 50 children with juvenile idiopathic arthritis (JIA) and 89
      healthy children were included. The Pediatric Quality of Life Inventory was used
      for HRQOL assessments. Anxiety symptoms were identified using the Screen for
      Child Anxiety-Related Emotional Disorders questionnaire, while depressive
      symptoms were identified using the Mood and Feeling Questionnaire. RESULTS:
      Children with PID had significantly lower Pediatric Quality of Life Inventory
      total scores compared to children with JIA and healthy children as child-rated
      (P=0.02) and parent-rated (P<0.001). Specifically, they had significantly lowered
      emotional functioning compared to children with JIA, and social functioning
      compared to both children with JIA and healthy children. School functioning was
      significantly lower among children with PID (parent-rated only). By parent-rated
      responses, six (24%) out of 25 children with PID had significant anxiety
      symptoms, while five (20%) children had significant depressive symptoms, which
      was statistically higher than among children with JIA and healthy controls
      (P=0.05). CONCLUSION: HRQOL could be significantly compromised in children with
      PID, particularly across such psychosocial domains as emotional, social, and
      school. These children were also found to be at an increased risk for suffering
      significant anxiety and depressive symptoms.

PMID- 24669190
TI  - Age-associated alterations in cholesterol homeostasis: evidence from a cross
      sectional study in a Northern Italy population.
AB  - BACKGROUND: The modifications of cholesterol metabolism associated with aging are
      ill-defined. The objective of this study was to define age-associated alterations
      of the different metabolic pathways controlling cholesterol homeostasis by
      analyzing circulating sterols. METHODS: We analyzed serum samples collected from
      201 adult (75 male, 126 female) subjects within the epidemiological MICOL study
      (Multicentrica Italiana Colelitiasi). The age range was 38-79 years; 103 had
      evidence of gallstones. The concentrations of the different sterols, recognized
      as markers of the main pathways of cholesterol homeostasis, were analyzed by gas
      chromatography-mass spectrometry, including lathosterol (synthesis), campesterol
      and sitosterol (absorption), and 7alpha-hydroxy-4-cholesten-3-one (degradation to
      bile acids). RESULTS: A significant direct correlation was detected between age
      and cholesterol levels (r =0.34, P<0.01). The lathosterol/cholesterol ratio was
      lower in older age quartiles (P<0.05 by analysis of variance), with an inverse
      correlation between the lathosterol/cholesterol ratio and age (r=-0.32, P<0.01).
      Such correlation was particularly evident in females. The campesterol/cholesterol
      and sitosterol/cholesterol ratios were inversely correlated with aging in
      control, but not in gallstone patients. The levels of 7alpha-hydroxy-4-cholesten
      3-one were not correlated with age. CONCLUSION: These data show a reduction of
      cholesterol synthesis with aging which is associated with increased circulating
      cholesterol levels. The finding might be related to a reduced metabolic need for
      cholesterol in advancing age, leading to a downregulation of the main mechanisms
      of cholesterol intake in the liver. A different age-related behavior was observed
      in gallstone-free versus gallstone patients regarding cholesterol absorption. The
      possible implications in terms of the pharmacological management of
      hypercholesterolemia in the elderly remain to be defined.

PMID- 24669192
TI  - Injection device-related risk management toward safe administration of
      medications: experience in a university teaching hospital in The People's
      Republic of China.
AB  - The use of injection devices to administer intravenous or subcutaneous
      medications is common practice throughout a variety of health care settings.
      Studies suggest that one-half of all harmful medication errors originate during
      drug administration; of those errors, about two-thirds involve injectables.
      Therefore, injection device management is pivotal to safe administration of
      medications. In this article, the authors summarize the relevant experiences by
      retrospective analysis of injection device-related near misses and adverse events
      in the Second Affiliated Hospital of Zhejiang University, School of Medicine,
      Zhejiang University, People's Republic of China. Injection device-related near
      misses and adverse events comprised the following: 1) improper selection of
      needle diameter for subcutaneous injection, material of infusion sets, and pore
      size of in-line filter; 2) complications associated with vascular access; 3)
      incidents induced by absence of efficient electronic pump management and infusion
      tube management; and 4) liquid leakage of chemotherapeutic infusion around the
      syringe needle. Safe injection drug use was enhanced by multidisciplinary
      collaboration, especially among pharmacists and nurses; drafting of clinical
      pathways in selection of vascular access; application of approaches such as root
      cause analysis using a fishbone diagram; plan-do-check-act and quality control
      circle; and construction of a culture of spontaneous reporting of near misses and
      adverse events. Pharmacists must be professional in regards to medication
      management and use. The depth, breadth, and efficiency of cooperation between
      nurses and pharmacists are pivotal to injection safety. 

PMID- 24669191
TI  - Bone plate composed of a ternary nano-hydroxyapatite/polyamide 66/glass fiber
      composite: biomechanical properties and biocompatibility.
AB  - An ideal bone plate for internal fixation of bone fractures should have good
      biomechanical properties and biocompatibility. In this study, we prepared a new
      nondegradable bone plate composed of a ternary nano-hydroxyapatite/polyamide
      66/glass fiber (n-HA/PA66/GF) composite. A breakage area on the n-HA/PA66/GF
      plate surface was characterized by scanning electron microscopy. Its mechanical
      properties were investigated using bone-plate constructs and biocompatibility was
      evaluated in vitro using bone marrow-derived mesenchymal stem cells. The results
      confirmed that adhesion between the n-HA/PA66 matrix and the glass fibers was
      strong, with only a few fibers pulled out at the site of breakage. Fractures
      fixed by the n-HA/PA66/GF plate showed lower stiffness and had satisfactory
      strength compared with rigid fixation using a titanium plate. Moreover, the
      results with regard to mesenchymal stem cell morphology, MTT assay, Alizarin Red
      S staining, enzyme-linked immunosorbent assay, and reverse transcription
      polymerase chain reaction for alkaline phosphatase and osteocalcin showed that
      the n-HA/PA66/GF composite was suitable for attachment and proliferation of
      mesenchymal stem cells, and did not have a negative influence on matrix
      mineralization or osteogenic differentiation of mesenchymal stem cells. These
      observations indicate that the n-HA/PA66/GF plate has good biomechanical
      properties and biocompatibility, and may be considered a new option for internal
      fixation in orthopedic surgery. 

PMID- 24669193
TI  - Cancer cell-oriented migration of mesenchymal stem cells engineered with an
      anticancer gene (PTEN): an imaging demonstration.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have been considered to hold great
      potential as ideal carriers for the delivery of anticancer agents since the
      discovery of their tumor tropism. This study was performed to demonstrate the
      effects of phosphatase and tensin homolog (PTEN) engineering on MSCs' capacity
      for cancer cell-oriented migration. METHODS: MSCs were engineered with a PTEN
      bearing plasmid and the expression was confirmed with Western blotting. A human
      glioma cell line (DBTRG) was used as the target cell; DBTRG cell-oriented
      migration of MSCs was monitored with a micro speed photographic system. RESULTS:
      The expression of transfected PTEN in MSCs was identified by immunoblotting
      analysis and confirmed with cell viability assessment of target cells. The DBTRG
      cell-oriented migration of PTEN-engineered MSCs was demonstrated by a real-time
      dynamic monitoring system, and a phagocytosis-like action of MSCs was also
      observed. CONCLUSION: MSCs maintained their capacity for cancer cell-directed
      migration after they were engineered with anticancer genes. This study provides
      the first direct evidence of MSCs' tropism post-anticancer gene engineering.

PMID- 24669195
TI  - Acupuncture and women's health: an overview of the role of acupuncture and its
      clinical management in women's reproductive health.
AB  - BACKGROUND: Acupuncture and other modalities of Chinese/East Asian medicine have
      been used to treat women's health for many centuries. Gynecology specialties
      focus particularly on menstrual and reproductive disorders. Both the adoption of
      the use of acupuncture outside Asia, and the incorporation of scientific analysis
      in Asia have challenged biomedical conceptions of what can be achieved with this
      treatment method. The scale of research activity in relation to acupuncture and
      women's health has increased over the last 20 years. OBJECTIVE: This review aims
      to explore the research evidence in relation to acupuncture use for women's
      reproductive disorders, focusing on both clinical findings and experimental
      research on acupuncture's mechanisms of action in relation to women's health.
      METHODS: A narrative literature search was undertaken using searches of
      electronic databases and manual searches of journals and textbooks. The search
      included all literature published prior to June 2013. The literature was assessed
      as to the nature of the study it was reporting and findings synthesized into a
      commentary. RESULTS: For acupuncture's mechanism of action the search resulted in
      114 relevant documents; in relation to clinical reports on the use of acupuncture
      for women's health 204 documents were found and assessed. CONCLUSION: There is
      preliminary data indicating acupuncture may improve menstrual health and coping
      for women experiencing delays falling pregnant. There is experimental data
      showing that acupuncture can influence female reproductive functioning, although
      the actual mechanisms involved are not yet clarified. Further well-conducted
      clinical research would benefit our understanding of the usefulness of
      acupuncture to women's health.

PMID- 24669196
TI  - First report of MRI findings in a case of an autoamputated wandering calcified
      ovary.
AB  - An autoamputated wandering calcified ovary (AWCO) is an extremely rare cause of
      abdominal calcification in the pediatric population. We present the magnetic
      resonance imaging (MRI) features of AWCO in a child. To our knowledge, the MRI
      features of AWCO have not been previously described in the published literature.
      Our case report indicates that the MRI findings are characteristic in the
      diagnosis of an AWCO and can completely obviate the need for invasive procedures
      in this mostly benign disease. An AWCO should be considered in all cases of
      mobile calcific opacities on radiographs in female patients. We advise that MRI
      be conducted in all suspected cases of AWCO for accurate and noninvasive
      diagnosis, and regular follow-up should be performed with ultrasound. The
      findings in our case report have the potential to change the course of
      investigations and management in suspected cases. 

PMID- 24669194
TI  - Community-acquired Clostridium difficile infection: an increasing public health
      threat.
AB  - There has been a startling shift in the epidemiology of Clostridium difficile
      infection over the last decade worldwide, and it is now increasingly recognized
      as a cause of diarrhea in the community. Classically considered a hospital
      acquired infection, it has now emerged in populations previously considered to be
      low-risk and lacking the traditional risk factors for C. difficile infection,
      such as increased age, hospitalization, and antibiotic exposure. Recent studies
      have demonstrated great genetic diversity for C. difficile, pointing toward
      diverse sources and a fluid genome. Environmental sources like food, water, and
      animals may play an important role in these infections, apart from the role
      symptomatic patients and asymptomatic carriers play in spore dispersal.
      Prospective strain typing using highly discriminatory techniques is a possible
      way to explore the suspected diverse sources of C. difficile infection in the
      community. Patients with community-acquired C. difficile infection do not
      necessarily have a good outcome and clinicians should be aware of factors that
      predict worse outcomes in order to prevent them. This article summarizes the
      emerging epidemiology, risk factors, and outcomes for community-acquired C.
      difficile infection. 

PMID- 24669197
TI  - A pilot evaluation of an online cognitive behavioral therapy for insomnia
      disorder - targeted screening and interactive Web design lead to improved sleep
      in a community population.
AB  - INTRODUCTION: Computerized or online cognitive behavioral therapies (CBTs) are
      increasingly being developed to deliver insomnia therapy (CBT-i). They seek to
      address the difficulty of delivering an evidence-based technology to a large
      number of patients at low cost. Previous online applications have shown
      significant but variable improvements in sleep efficiency and a decrease in
      insomnia severity when compared with control groups. The best online methodology
      remains debated, and there are no such applications currently available within
      the UK National Health Service. METHOD: Evaluation of treatment outcomes in 75
      participants with insomnia disorder using an open-access, novel, interactive
      online therapy. Rigorous screening was first undertaken to exclude those with
      probable sleep apnea, restless legs, circadian rhythm disorder, or significant
      anxiety or depression prior to commencing therapy. A modern interactive video
      based website was used to encourage compliance by personalizing therapy based on
      response. Sleep efficiency, sleep latency, total sleep time, and sleep quality
      were all assessed prior to and after intervention. RESULTS: Of those who accessed
      therapy, 62% were excluded based on a likely diagnosis of another sleep disorder
      (788/1281). Participants who completed therapy all had severe insomnia disorder,
      with a group mean sleep efficiency of 55%. After intervention there was a
      significant increase in sleep efficiency and sleep latency, with modest
      nonsignificant improvements in total sleep time. The majority of users reported
      improved sleep quality, and compliance with therapy was very good, with over
      64/75 completing >90% of sleep diary entries. CONCLUSION: Online CBT-i can be
      designed to deliver personalized therapy with good reported outcomes and high
      compliance rates in those who start therapy. This initial evaluation also
      suggests that screening for other sleep disorders and mental health problems is
      necessary as many other sleep disorders are detected in those who self-refer with
      insomnia. This would inform the development of any larger-scale applications
      within the psychological therapies used in the health care system.

PMID- 24669198
TI  - Mutations in PRSS1 put into perspective.

PMID- 24669199
TI  - Different isolation methods alter the gene expression profiling of adipose
      derived stem cells.
AB  - Human adipose stem cells (ASCs) has been in the limelight since its discovery as
      a suitable source of mesenchymal stem cells (MSCs) in regenerative medicine.
      Currently, two major techniques are used to isolate ASCs, namely liposuction and
      tissue biopsy. These two methods are relatively risk-free but the question as to
      which method could give a more efficient output remains unclear. Thus, this study
      was carried out to compare and contrast the output generated in regards to growth
      kinetics, differentiation capabilities in vitro, and gene expression profiling.
      It was found that ASCs from both isolation methods were comparable in terms of
      growth kinetics and tri-lineage differentiation. Furthermore, ASCs from both
      populations were reported as CD44(+), CD73(+), CD90(+), CD166(+), CD34(-), CD45(
      ) and HLA-DR(-). However, in regards to gene expression, a group of overlapping
      genes as well as distinct genes were observed. Distinct gene expressions
      indicated that ASCs (liposuction) has endoderm lineage propensity whereas ASCs
      (biopsy) has a tendency towards mesoderm/ectoderm lineage. This information
      suggests involvement in different functional activity in accordance to isolation
      method. In conclusion, future studies to better understand these gene functions
      should be carried out in order to contribute in the applicability of each
      respective cells in regenerative therapy. 

PMID- 24669200
TI  - Characterization of ten heterotetrameric NDP-dependent acyl-CoA synthetases of
      the hyperthermophilic archaeon Pyrococcus furiosus.
AB  - The hyperthermophilic archaeon Pyrococcus furiosus grows by fermenting peptides
      and carbohydrates to organic acids. In the terminal step, acyl-CoA synthetase
      (ACS) isoenzymes convert acyl-CoA derivatives to the corresponding acid and
      conserve energy in the form of ATP. ACS1 and ACS2 were previously purified from
      P. furiosus and have alpha 2 beta 2 structures but the genome contains genes
      encoding three additional alpha-subunits. The ten possible combinations of alpha
      and beta genes were expressed in E. coli and each resulted in stable and active
      alpha 2 beta 2 isoenzymes. The alpha-subunit of each isoenzyme determined CoA
      based substrate specificity and between them they accounted for the CoA
      derivatives of fourteen amino acids. The beta-subunit determined preference for
      adenine or guanine nucleotides. The GTP-generating isoenzymes are proposed to
      play a role in gluconeogenesis by producing GTP for GTP-dependent
      phosphoenolpyruvate carboxykinase and for other GTP-dependent processes.
      Transcriptional and proteomic data showed that all ten isoenzymes are
      constitutively expressed indicating that both ATP and GTP are generated from the
      metabolism of most of the amino acids. A phylogenetic analysis showed that the
      ACSs of P. furiosus and other members of the Thermococcales are evolutionarily
      distinct from those found throughout the rest of biology, including those of
      other hyperthermophilic archaea. 

PMID- 24669201
TI  - The alternative route to heme in the methanogenic archaeon Methanosarcina
      barkeri.
AB  - In living organisms heme is formed from the common precursor uroporphyrinogen III
      by either one of two substantially different pathways. In contrast to eukaryotes
      and most bacteria which employ the so-called "classical" heme biosynthesis
      pathway, the archaea use an alternative route. In this pathway, heme is formed
      from uroporphyrinogen III via the intermediates precorrin-2, sirohydrochlorin,
      siroheme, 12,18-didecarboxysiroheme, and iron-coproporphyrin III. In this study
      the heme biosynthesis proteins AhbAB, AhbC, and AhbD from Methanosarcina barkeri
      were functionally characterized. Using an in vivo enzyme activity assay it was
      shown that AhbA and AhbB (Mbar_A1459 and Mbar_A1460) together catalyze the
      conversion of siroheme into 12,18-didecarboxysiroheme. The two proteins form a
      heterodimeric complex which might be subject to feedback regulation by the
      pathway end-product heme. Further, AhbC (Mbar_A1793) was shown to catalyze the
      formation of iron-coproporphyrin III in vivo. Finally, recombinant AhbD
      (Mbar_A1458) was produced in E. coli and purified indicating that this protein
      most likely contains two [4Fe-4S] clusters. Using an in vitro enzyme activity
      assay it was demonstrated that AhbD catalyzes the conversion of iron
      coproporphyrin III into heme. 

PMID- 24669204
TI  - Neurobiological consequences of oxidative stress.

PMID- 24669202
TI  - Unique characteristics of the pyrrolysine system in the 7th order of methanogens:
      implications for the evolution of a genetic code expansion cassette.
AB  - Pyrrolysine (Pyl), the 22nd proteogenic amino acid, was restricted until recently
      to few organisms. Its translational use necessitates the presence of enzymes for
      synthesizing it from lysine, a dedicated amber stop codon suppressor tRNA, and a
      specific amino-acyl tRNA synthetase. The three genomes of the recently proposed
      Thermoplasmata-related 7th order of methanogens contain the complete genetic set
      for Pyl synthesis and its translational use. Here, we have analyzed the genomic
      features of the Pyl-coding system in these three genomes with those previously
      known from Bacteria and Archaea and analyzed the phylogeny of each component.
      This shows unique peculiarities, notably an amber tRNA(Pyl) with an imperfect
      anticodon stem and a shortened tRNA(Pyl) synthetase. Phylogenetic analysis
      indicates that a Pyl-coding system was present in the ancestor of the seventh
      order of methanogens and appears more closely related to Bacteria than to
      Methanosarcinaceae, suggesting the involvement of lateral gene transfer in the
      spreading of pyrrolysine between the two prokaryotic domains. We propose that the
      Pyl-coding system likely emerged once in Archaea, in a hydrogenotrophic and
      methanol-H2-dependent methylotrophic methanogen. The close relationship between
      methanogenesis and the Pyl system provides a possible example of expansion of a
      still evolving genetic code, shaped by metabolic requirements. 

PMID- 24669205
TI  - Glucocorticoid regulates parkin expression in mouse frontal cortex: implications
      in schizophrenia.
AB  - Stress and glucocorticoid hormones, which are released into the circulation
      following stressful experiences, have been shown to contribute significantly to
      the manifestation of various psychiatric illnesses including schizophrenia and
      depression. Studies in rodents have reported dose and time dependent effects of
      glucocorticoids on the expression of proteins related to neuroplasticity.
      However, the mechanism(s) involved in the regulation of proteins by
      glucocorticoids are not clear. Ubiquitin ligases play important role in
      degradation, trafficking and stabilization of proteins. The present study
      investigated the effect of glucocorticoid on ubiquitin-proteasome system in mouse
      frontal cortex. A significant increase in mRNA and protein levels of parkin, an
      E3 ubiquitin ligase was found in cultured mouse primary cortical neurons
      following corticosterone treatment. An increase in parkin levels was also found
      in mouse frontal cortex in vivo following acute dexamethasone treatment. However,
      chronic treatment with corticosterone did not change parkin protein levels in
      mouse frontal cortex. Studies using postmortem brain samples from schizophrenia
      and control subjects indicated a significant increase in parkin protein levels in
      frontal cortex of schizophrenia subjects suggesting a response to increased
      stress conditions in schizophrenia. These findings suggest a possible role of
      parkin in the pathophysiology of stress-related psychiatric disorders. 

PMID- 24669206
TI  - Novel therapeutic targets in depression and anxiety: antioxidants as a candidate
      treatment.
AB  - There is growing evidence that the imbalance between oxidative stress and the
      antioxidant defense system may be associated with the development
      neuropsychiatric disorders, such as depression and anxiety. Major depression and
      anxiety are presently correlated with a lowered total antioxidant state and by an
      activated oxidative stress (OS) pathway. The classical antidepressants may
      produce therapeutic effects other than regulation of monoamines by increasing the
      antioxidant levels and normalizing the damage caused by OS processes. This
      chapter provides an overview of recent work on oxidative stress markers in the
      animal models of depression and anxiety, as well as patients with the
      aforementioned mood disorders. It is well documented that antioxidants can remove
      the reactive oxygen species (ROS) and reactive nitrogen species (RNS) through
      scavenging radicals and suppressing the OS pathway, which further protect against
      neuronal damage caused oxidative or nitrosative stress sources in the brain,
      hopefully resulting in remission of depression or anxiety symptoms. The
      functional understanding of the relationship between oxidative stress and
      depression and anxiety may pave the way for discovery of novel targets for
      treatment of neuropsychiatric disorders. 

PMID- 24669207
TI  - Association of oxidative stress to the genesis of anxiety: implications for
      possible therapeutic interventions.
AB  - Oxidative stress caused by reactive species, including reactive oxygen species,
      reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe]
      and copper [Cu]), is an underlying cause of various neurodegenerative diseases.
      These reactive species are an inevitable by-product of cellular respiration or
      other metabolic processes that may cause the oxidation of lipids, nucleic acids,
      and proteins. Oxidative stress has recently been implicated in depression and
      anxiety-related disorders. Furthermore, the manifestation of anxiety in numerous
      psychiatric disorders, such as generalized anxiety disorder, depressive disorder,
      panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress
      disorder, highlights the importance of studying the underlying biology of these
      disorders to gain a better understanding of the disease and to identify common
      biomarkers for these disorders. Most recently, the expression of glutathione
      reductase 1 and glyoxalase 1, which are genes involved in antioxidative
      metabolism, were reported to be correlated with anxiety-related phenotypes. This
      review focuses on direct and indirect evidence of the potential involvement of
      oxidative stress in the genesis of anxiety and discusses different opinions that
      exist in this field. Antioxidant therapeutic strategies are also discussed,
      highlighting the importance of oxidative stress in the etiology, incidence,
      progression, and prevention of psychiatric disorders. 

PMID- 24669208
TI  - Oxidative stress and psychological disorders.
AB  - Oxidative stress is an imbalance between cellular production of reactive oxygen
      species and the counteracting antioxidant mechanisms. The brain with its high
      oxygen consumption and a lipid-rich environment is considered highly susceptible
      to oxidative stress or redox imbalances. Therefore, the fact that oxidative
      stress is implicated in several mental disorders including depression, anxiety
      disorders, schizophrenia and bipolar disorder, is not surprising. Although
      several elegant studies have established a link between oxidative stress and
      psychiatric disorders, the causal relationship between oxidative stress and
      psychiatric diseases is not fully determined. Another critical aspect that needs
      much attention and effort is our understanding of the association between
      cellular oxidative stress and emotional stress. This review examines some of the
      recent discoveries that link oxidative status with anxiety, depression,
      schizophrenia and bipolar disorder. A discussion of published results and
      questions that currently exist in the field regarding a causal relationship
      between oxidative and emotional stress is also provided. 

PMID- 24669211
TI  - Metformin Eased Cognitive Impairment Induced by Chronic L-methionine
      Administration: Potential Role of Oxidative Stress.
AB  - Chronic administration of L-methionine leads to memory impairment, which is
      attributed to increase in the level of oxidative stress in the brain. On the
      other hand, metformin is a commonly used antidiabetic drug with strong
      antioxidant properties. In the current study, we tested if chronic metformin
      administration prevents memory impairment induced by administration of L
      methionine. In addition, a number of molecules related to the action of metformin
      on cognitive functions were examined. Both metformin and L-methionine were
      administered to animals by oral gavage. Testing of spatial learning and memory
      was carried out using radial arm water maze (RAWM). Additionally, hippocampal
      levels or activities of catalase, thiobarbituric acid reactive substances
      (TBARs), glutathione peroxidase (GPx), glutathione (GSH), oxidized glutathione
      (GSSG) and GSH/GSSG ratio were determined. Results showed that chronic L
      methionine administration resulted in both short- and long- term memory
      impairment, whereas metformin treatment prevented such effect. Additionally, L
      methionine treatment induced significant elevation in GSSG and TBARs, along with
      reduction in GSH/GSSG ratio and activities of catalase, and GPx. These effects
      were shown to be restored by metformin treatment. In conclusion, L-methionine
      induced memory impairment, and treatment with metformin prevented this impairment
      probably by normalizing oxidative stress in the hippocampus. 

PMID- 24669209
TI  - Redox Regulation and the Autistic Spectrum: Role of Tryptophan Catabolites,
      Immuno-inflammation, Autoimmunity and the Amygdala.
AB  - The autistic spectrum disorders (ASD) form a set of multi-faceted disorders with
      significant genetic, epigenetic and environmental determinants. Oxidative and
      nitrosative stress (O&NS), immuno-inflammatory pathways, mitochondrial
      dysfunction and dysregulation of the tryptophan catabolite (TRYCATs) pathway play
      significant interactive roles in driving the early developmental etiology and
      course of ASD. O&NS interactions with immuno-inflammatory pathways mediate their
      effects centrally via the regulation of astrocyte and microglia responses,
      including regional variations in TRYCATs produced. Here we review the nature of
      these interactions and propose an early developmental model whereby different ASD
      genetic susceptibilities interact with environmental and epigenetic processes,
      resulting in glia biasing the patterning of central interarea interactions. A
      role for decreased local melatonin and N-acetylserotonin production by immune and
      glia cells may be a significant treatment target. 

PMID- 24669214
TI  - Graphical abstracts.

PMID- 24669213
TI  - Individual differences in the neurobiology of social stress: implications for
      depression-cardiovascular disease comorbidity.
AB  - Stress initiates a cascade of complex neural and peripheral changes that promote
      healthy adaption to stress, but when unabated, leads to pathology. Fascinating
      individual differences arise in the ability to cope with a stressor, rendering an
      individual more or less likely to develop stress-induced pathologies such as
      depression, anxiety, and cardiovascular disease. In this review we evaluate
      recent findings that investigate the neural underpinnings of adopting a passive
      or active coping response during social defeat stress. Because passive coping is
      associated with vulnerability to stress-related pathologies and active coping
      confers resiliency, understanding neurobiological adaptations associated with
      these diverse coping strategies may reveal biomarkers or targets impacting stress
      susceptibility. The co-occurrence of stress-induced depression and cardiovascular
      disease is becoming increasingly clear. Therefore this review focuses on the
      central mechanisms capable of contributing to psychopathology and cardiovascular
      disease such as corticotropin releasing factor, neuropeptide Y, monoamines,
      cytokines and oxidative stress. The impetus for this review is to highlight
      neurobiological systems that warrant further evaluation for their contribution to
      the pathophysiology of depression-cardiovascular disease comorbidity. 

PMID- 24669215
TI  - Clinicopathological and prognostic characteristics of hepatoid adenocarcinoma of
      the stomach.
AB  - The present study was undertaken to clarify the association of the
      clinicopathological features of hepatoid adenocarcinoma (HAC) in the stomach, a
      special kind of carcinoma that histologically resembled hepatocellular carcinoma
      (HCC) and is characterized by large amounts of alpha -fetoprotein (AFP) in serum,
      with the clinical prognosis. We collected the data of the clinicopathological
      features and the follow-up information from a total of 31 HACs from January 2005
      to December 2012 in our hospital. High lymphatic (54.8%) and distant (25.8%)
      metastasis rates before surgery, large proportion of advanced HACs (71.0%) at
      admission, short median overall survival time (6 months), and low three-year
      survival rate (22.6%) suggested that HAC in the stomach was an aggressive
      disease, resulting in a poor prognosis. And pTNM stages, immunohistochemical
      staining of AFP, CEA, CK7, and CK20 had statistically relation with the survival
      as the independent risk factors, P < 0.05. Therefore, early and clear
      differentiation of HAC from cancerous or noncancerous conditions with AFP
      elevation and assessment of high risk patients by histopathology may improve the
      clinical prognosis. 

PMID- 24669210
TI  - Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients
      with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS).
AB  - Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been
      classified as a disease of the central nervous system by the WHO since 1969. Many
      patients carrying this diagnosis do demonstrate an almost bewildering array of
      biological abnormalities particularly the presence of oxidative and nitrosative
      stress (O&NS) and a chronically activated innate immune system. The proposal made
      herein is that once generated chronically activated O&NS and immune-inflammatory
      pathways conspire to generate a multitude of self-sustaining and self-amplifying
      pathological processes which are associated with the onset of ME/CFS. Sources of
      continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are
      chronic, intermittent and opportunistic infections, bacterial translocation,
      autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like
      Receptor Radical Cycle, and decreased antioxidant levels. Consequences of
      chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain
      disorders, including neuroinflammation and brain hypometabolism / hypoperfusion,
      toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative
      damage to DNA, secondary autoimmune responses directed against disrupted lipid
      membrane components and proteins, mitochondrial dysfunctions with a disruption of
      energy metabolism (e.g. compromised ATP production) and dysfunctional
      intracellular signaling pathways. The interplay between all of these factors
      leads to self-amplifying feed forward loops causing a chronic state of activated
      O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease. 

PMID- 24669212
TI  - Oxidative imbalance and anxiety disorders.
AB  - The oxidative imbalance appears to have an important role in anxiety development.
      Studies in both humans and animals have shown a strong correlation between
      anxiety and oxidative stress. In humans, for example, the increased
      malondialdehyde levels and discrepancies in antioxidant enzymes in erythrocytes
      have been observed. In animals, several studies also show that anxiety-like
      behavior is related to the oxidative imbalance. Moreover, anxiety-like behavior
      can be caused by pharmacological-induced oxidative stress. Studies using knockout
      or overexpression of antioxidant enzymes have shown a relationship between
      anxiety-like behavior and oxidative stress. Related factors of oxidative stress
      that could influence anxious behavior are revised, including impaired function of
      different mitochondrial proteins, inflammatory cytokines, and neurotrophic
      factors. It has been suggested that a therapy specifically focus in reducing
      reactive species production may have a beneficial effect in reducing anxiety.
      However, the neurobiological pathways underlying the effect of oxidative stress
      on anxiety symptoms are not fully comprehended. The challenge now is to identify
      the oxidative stress mechanisms likely to be involved in the induction of anxiety
      symptoms. Understanding these pathways could help to clarify the neurobiology of
      the anxiety disorder and provide tools for new discovery in therapies and
      preventive strategies. 

PMID- 24669216
TI  - Trapa bispinosa Roxb.: A Review on Nutritional and Pharmacological Aspects.
AB  - Trapa bispinosa Roxb. which belongs to the family Trapaceae is a small herb well
      known for its medicinal properties and is widely used worldwide. Trapa bispinosa
      or Trapa natans is an important plant of Indian Ayurvedic system of medicine
      which is used in the problems of stomach, genitourinary system, liver, kidney,
      and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge, and
      antiseptic. The whole plant is used in gonorrhea, menorrhagia, and other genital
      affections. It is useful in diarrhea, dysentery, ophthalmopathy, ulcers, and
      wounds. These are used in the validated conditions in pitta, burning sensation,
      dipsia, dyspepsia, hemorrhage, hemoptysis, diarrhea, dysentery, strangely,
      intermittent fever, leprosy, fatigue, inflammation, urethrorrhea, fractures,
      erysipelas, lumbago, pharyngitis, bronchitis and general debility, and
      suppressing stomach and heart burning. Maybe it is due to photochemical content
      of Trapa bispinosa having high quantity of minerals, ions, namely, Ca, K, Na, Zn,
      and vitamins; saponins, phenols, alkaloids, H-donation, flavonoids are reported
      in the plants. Nutritional and biochemical analyses of fruits of Trapa bispinosa
      in 100 g showed 22.30 and 71.55% carbohydrate, protein contents were 4.40% and
      10.80%, a percentage of moisture, fiber, ash, and fat contents were 70.35 and
      7.30, 2.05 and 6.35, 2.30 and 8.50, and 0.65 and 1.85, mineral contents of the
      seeds were 32 mg and 102.85 mg calcium, 1.4 and 3.8 mg Iron, and 121 and 325 mg
      phosphorus in 100 g, and seeds of Trapa bispinosa produced 115.52 and 354.85 Kcal
      of energy, in fresh and dry fruits, respectively. Chemical analysis of the fruit
      and fresh nuts having considerable water content citric acid and fresh fruit
      which substantiates its importance as dietary food also reported low crude lipid,
      and major mineral present with confirming good amount of minerals as an iron and
      manganese potassium were contained in the fruit. Crude fiber, total protein
      content of the water chestnut kernel, Trapa bispinosa are reported. In this
      paper, the recent reports on nutritional, phytochemical, and pharmacological
      aspects of Trapa bispinosa Roxb, as a medicinal and nutritional food, are
      reviewed. 

PMID- 24669218
TI  - Disseminated tumor cells in bone marrow of gastric cancer patients: correlation
      with tumor hypoxia and clinical relevance.
AB  - Aim. The evaluation of the clinical relevance of disseminated tumor cells (DTCs)
      in bone marrow (BM) of patients with gastric cancer (GC) and their association
      with primary tumor hypoxia. Patients and Methods. 89 resected specimens were
      used. DTCs were detected using immunocytochemistry, the level of tumor hypoxia
      using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using
      immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. Results.
      DTCs were detected in 51.4% of GC patients with M0. There was significant
      correlation between frequency of DTCs in BM and level of tumor hypoxia (P <
      0.024). DTCs presence was accompanied with Flt-1 positivity of BM. The
      correlation between DTCs and tumor VEGF expression in patients with M0 was shown
      (P < 0.0248). Activity of MMP-2 and MMP-9 in BM was linked with DTCs in patients
      with M0 (P < 0.05). Overall survival (OS) of patients with M0 and DTCs was
      shorter than that of patients without DTCs (patients in both groups were operated
      only) (P = 0.0497). Conclusion. Appearance of DTCs correlates with hypoxia level
      in primary tumors. Detection of DTCs in GC patients may be relevant indicator for
      adjuvant chemotherapy using. 

PMID- 24669217
TI  - Hemozoin inhibition and control of clinical malaria.
AB  - Malaria has a negative impact on health and social and economic life of residents
      of endemic countries. The ultimate goals of designing new treatment for malaria
      are to prevent clinical infection, reduce morbidity, and decrease mortality.
      There are great advances in the understanding of the parasite-host interaction
      through studies by various scientists. In some of these studies, attempts were
      made to evaluate the roles of malaria pigment or toxins in the pathogenesis of
      malaria. Hemozoin is a key metabolite associated with severe malaria anemia
      (SMA), immunosuppression, and cytokine dysfunction. Targeting of this pigment may
      be necessary in the design of new therapeutic products against malaria. In this
      review, the roles of hemozoin in the morbidity and mortality of malaria are
      highlighted as an essential target in the quest for effective control of clinical
      malaria. 

PMID- 24669219
TI  - Gastrointestinal Bacterial and Methanogenic Archaea Diversity Dynamics Associated
      with Condensed Tannin-Containing Pine Bark Diet in Goats Using 16S rDNA Amplicon
      Pyrosequencing.
AB  - Eighteen Kiko-cross meat goats (n = 6) were used to collect gastrointestinal (GI)
      bacteria and methanogenic archaea for diversity measures when fed condensed
      tannin-containing pine bark (PB). Three dietary treatments were tested: control
      diet (0% PB and 30% wheat straw (WS); 0.17% condensed tannins (CT) dry matter
      (DM)); 15% PB and 15% WS (1.6% CT DM), and 30% PB and 0% WS (3.2% CT DM). A 16S
      rDNA bacterial tag-encoded FLX amplicon pyrosequencing technique was used to
      characterize and elucidate changes in GI bacteria and methanogenic archaea
      diversity among the diets. Proteobacteria was the most dominant phylum in goats
      with mean relative abundance values ranging from 39.7 (30% PB) to 46.5% (control)
      and 47.1% (15% PB). Other phyla individually accounted for fewer than 25% of the
      relative abundance observed. Predominant methanogens were Methanobrevibacter (75,
      72, and 49%), Methanosphaera (3.3, 2.3, and 3.4%), and Methanobacteriaceae (1.2,
      0.6, and 0.7%) population in control, 15, and 30% PB, respectively. Among
      methanogens, Methanobrevibacter was linearly decreased (P = 0.05) with increasing
      PB supplementation. These results indicate that feeding PB selectively altered
      bacteria and methanogenic archaeal populations in the GI tract of goats. 

PMID- 24669220
TI  - Effect of noradrenaline on the virulence properties of campylobacter species.
AB  - Campylobacter species cause a spectrum of illnesses in humans. The type of
      illness and the outcome is dependent on the virulence of the infecting pathogen
      strain and host immune status. Acute stress can seriously compromise host
      immunity and increase susceptibility to infection. Noradrenaline (NA) is a stress
      hormone. Several studies have shown that it stimulated growth and increased the
      pathogenicity of organisms including E. coli and Campylobacter jejuni. However,
      the effect of NA on other Campylobacter species is unknown. We have examined the
      effect of NA on growth rate, motility, invasion of T84 epithelial cells, and
      colonisation of chickens by diverse Campylobacter species. Campylobacter cultures
      grown with NA had reduced lag phases, increased growth rates, and higher final
      optical densities than controls. The motility of Campylobacter was also
      significantly increased in the presence of noradrenaline. Some of the
      Campylobacter strains tested also showed increased invasion of T84 epithelial
      cells, greater breakdown of tight junctions, and an enhanced potential to
      colonise chickens. Our results show that noradrenaline-induced enhancement of
      virulence of Campylobacter can influence the outcome of infection. 

PMID- 24669221
TI  - Molecular analysis of human metapneumovirus detected in patients with lower
      respiratory tract infection in upper egypt.
AB  - Introduction. Since 2001, when Human metapneumovirus (HMPV) was isolated in the
      Netherlands, the virus has been detected in several continents. Although reports
      have confirmed the prevalence of HMPV worldwide, data from Egypt remain limited.
      HMPV plays an important role in respiratory tract infections in individuals of
      all ages particularly in children. This study was aimed at estimating the
      prevalence of HMPV in patients with community-acquired lower respiratory
      infection in Upper Egypt and characterizing the circulating Egyptian HMPV strains
      for the first time. Materials and Methods. From 2005 to 2008, respiratory samples
      from 520 patients were analyzed for the presence of HMPV by real-time RT-PCR.
      Molecular and phylogenetic analyses were performed on partial fusion gene
      sequences of HMPV-positive patients. Results. HMPV-positive patients were
      detected in 2007-2008. The overall infection rate was 4%, while 57% of the
      patients were children. Sequence analysis demonstrated circulation of subgroup B
      viruses with predominance of lineage B2. Nucleotide sequence identity within
      lineage B1 was 98.8%-99.7% and higher than that in lineage B2 (94.3%-100%). Three
      new amino acid substitutions (T223N, R229K, and D280N) of lineage B2 were
      observed. Conclusion. HMPV is a major viral pathogen in the Egyptian population
      especially in children. During 2007-2008, predominantly HMPV B2 circulated in
      Upper Egypt. 

PMID- 24669222
TI  - Evaluation of phytase producing bacteria for their plant growth promoting
      activities.
AB  - Bacterial inoculants are known to possess plant growth promoting abilities and
      have potential as liquid biofertilizer application. Four phytase producing
      bacterial isolates (phytase activity in the range of 0.076-0.174 U/mL),
      identified as Advenella species (PB-05, PB-06, and PB-10) and Cellulosimicrobium
      sp. PB-09, were analyzed for their plant growth promoting activities like
      siderophore production, IAA production, HCN production, ammonia production,
      phosphate solubilization, and antifungal activity. All isolates were positive for
      the above characteristics except for HCN production. The solubilization index for
      phosphorus on Pikovskaya agar plates was in the range of 2-4. Significant amount
      of IAA (7.19 to 35.03  MU g/mL) production and solubilized phosphate (189.53 to
      746.84  MU g/mL) was noticed by these isolates at different time intervals.
      Besides that, a greenhouse study was also conducted with Indian mustard to
      evaluate the potential of these isolates to promote plant growth. Effect of seed
      bacterization on various plant growth parameters and P uptake by plant were used
      as indicators. The plant growth promoting ability of bacterial isolates in pot
      experiments was correlated to IAA production, phosphate solubilization, and other
      in vitro tests. On the basis of present findings, isolate PB-06 was most
      promising in plant growth promotion with multiple growth promoting
      characteristics. 

PMID- 24669223
TI  - Hormetic concentrations of hydrogen peroxide but not ethanol induce cross
      adaptation to different stresses in budding yeast.
AB  - The biphasic-dose response of microorganisms to hydrogen peroxide is a phenomenon
      of particular interest in hormesis research. In different animal models, the dose
      response curve for ethanol is also nonlinear showing an inhibitory effect at high
      doses but a stimulatory effect at low doses. In this study, we observed the
      hormetic-dose response to ethanol in budding yeast S. cerevisiae. Cross
      protection is a phenomenon in which exposure to mild stress results in the
      acquisition of cellular resistance to lethal stress induced by different factors.
      Since both hydrogen peroxide and ethanol at low concentrations were found to
      stimulate yeast colony growth, we evaluated the role of one substance in cell
      cross-adaptation to the other substance as well as some weak organic acid
      preservatives. This study demonstrates that, unlike ethanol, hydrogen peroxide at
      hormetic concentrations causes cross-resistance of S. cerevisiae to different
      stresses. The regulatory protein Yap1 plays an important role in the hormetic
      effects by low concentrations of either hydrogen peroxide or ethanol, and it is
      involved in the yeast cross-adaptation by low sublethal doses of hydrogen
      peroxide. 

PMID- 24669224
TI  - High Level Expression and Purification of Atl, the Major Autolytic Protein of
      Staphylococcus aureus.
AB  - Staphylococcus aureus is a major human and animal pathogen. Autolysins regulate
      the growth, turnover, cell lysis, biofilm formation, and the pathogenicity of S.
      aureus. Atl is the major autolysin in S. aureus. The biochemical and structural
      studies of staphylococcal Atl have been limited due to difficulty in cloning,
      high level overexpression, and purification of this protein. This study describes
      successful cloning, high level over-expression, and purification of two forms of
      fully functional Atl proteins. These pure proteins can be used to study the
      functional and structural properties of this important protein. 

PMID- 24669225
TI  - Simultaneous Production of Biosurfactants and Bacteriocins by Probiotic
      Lactobacillus casei MRTL3.
AB  - Lactic acid bacteria (LAB) are ubiquitous and well-known commensal bacteria in
      the human and animal microflora. LAB are extensively studied and used in a
      variety of industrial and food fermentations. They are widely used for humans and
      animals as adjuvants, probiotic formulation, and dietary supplements and in other
      food fermentation applications. In the present investigation, LAB were isolated
      from raw milk samples collected from local dairy farms of Haryana, India.
      Further, the isolates were screened for simultaneous production of biosurfactants
      and bacteriocins. Biosurfactant produced was found to be a mixture of lipid and
      sugar similar to glycolipids. The bacteriocin obtained was found to be heat
      stable (5 min at 100 degrees C). Further, DNA of the strain was extracted and
      amplified by the 16S rRNA sequencing using universal primers. The isolate
      Lactobacillus casei MRTL3 was found to be a potent biosurfactant and bacteriocin
      producer. It seems to have huge potential for food industry as a biopreservative
      and/or food ingredient. 

PMID- 24669226
TI  - Blood politics, ethnic identity, and racial misclassification among American
      Indians and Alaska Natives.
AB  - Misclassification of race in medical and mortality records has long been
      documented as an issue in American Indian/Alaska Native data. Yet, little has
      been shared in a cohesive narrative which outlines why misclassification of
      American Indian/Alaska Native identity occurs. The purpose of this paper is to
      provide a summary of the current state of the science in racial misclassification
      among American Indians and Alaska Natives. We also provide a historical context
      on the importance of this problem and describe the ongoing political processes
      that both affect racial misclassification and contribute to the context of
      American Indian and Alaska Native identity. 

PMID- 24669228
TI  - Deciphering molecular mechanism underlying hypolipidemic activity of echinocystic
      Acid.
AB  - Our previous study showed that a triterpene mixture, consisting of echinocystic
      acid (EA) and oleanolic acid (OA) at a ratio of 4 : 1, dose-dependently
      ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high
      fat/high cholesterol diets. This study was aimed at exploring the mechanisms
      underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA
      was performed using Molegro Virtual Docker (version: 4.3.0) to investigate the
      potential targets related to lipid metabolism. Based on the molecular docking
      information, isotope labeling method or spectrophotometry was applied to examine
      the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase, acyl-CoA:cholesterol acyltransferase (ACAT), and diacylglycerol
      acyltransferase (DGAT) in rat liver microsomes. Our results revealed a strong
      affinity of EA towards ACAT and DGAT in molecular docking analysis, while low
      binding affinity existed between EA and HMG-CoA reductase as well as between EA
      and cholesteryl ester transfer protein. Consistent with the results of molecular
      docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT,
      with IC50 values of 103 and 139  MU M, respectively, and exhibited no significant
      effect on HMG-CoA reductase activity. The present findings suggest that EA may
      exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT. 

PMID- 24669227
TI  - Antioxidant and anti-inflammatory activities of berberine in the treatment of
      diabetes mellitus.
AB  - Oxidative stress and inflammation are proved to be critical for the pathogenesis
      of diabetes mellitus. Berberine (BBR) is a natural compound isolated from plants
      such as Coptis chinensis and Hydrastis canadensis and with multiple
      pharmacological activities. Recent studies showed that BBR had antioxidant and
      anti-inflammatory activities, which contributed in part to its efficacy against
      diabetes mellitus. In this review, we summarized the antioxidant and anti
      inflammatory activities of BBR as well as their molecular basis. The antioxidant
      and anti-inflammatory activities of BBR were noted with changes in oxidative
      stress markers, antioxidant enzymes, and proinflammatory cytokines after BBR
      administration in diabetic animals. BBR inhibited oxidative stress and
      inflammation in a variety of tissues including liver, adipose tissue, kidney and
      pancreas. Mechanisms of the antioxidant and anti-inflammatory activities of BBR
      were complex, which involved multiple cellular kinases and signaling pathways,
      such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinases
      (MAPKs), nuclear factor erythroid-2-related factor-2 (Nrf2) pathway, and nuclear
      factor- kappa B (NF- kappa B) pathway. Detailed mechanisms and pathways for the
      antioxidant and anti-inflammatory activities of BBR still need further
      investigation. Clarification of these issues could help to understand the
      pharmacology of BBR in the treatment of diabetes mellitus and promote the
      development of antidiabetic natural products. 

PMID- 24669229
TI  - An overview of systematic reviews of shenmai injection for healthcare.
AB  - Shenmai injection (SMI) is widely applied in clinical practice as an organ
      protector. This overview is to evaluate the current evidence from systematic
      reviews (SRs) of SMI for healthcare. The literature searches were carried out in
      6 databases without language restrictions until December 2012. The quality of the
      primary studies from the respective SRs was evaluated by using Jadad score. The
      overview quality assessment questionnaire (OQAQ) was used to evaluate the
      methodological quality of all included SRs. Twenty eligible SRs were identified.
      They reported a wide range of conditions, including SMI for
      cardio/cerebrovascular diseases, viral myocarditis, tumor chemotherapy, and
      adverse drug reactions. Most of the primary studies were of good quality only in
      1 SR of non-small-cell lung cancer. According to the OQAQ scores, the quality of
      included SRs was variable and six reviews were of high quality with a score of 5
      points. Two SRs showed that SMI had low adverse drug reaction occurrence. In
      conclusion, there is mixed evidence to support efficacy of SMI for an adjunct
      therapy to tumor chemotherapy and premature evidence for the use of SMI for
      cardio/cerebrovascular disorders and viral myocarditis. SMI seems generally safe
      for clinical application. Further large sample-size and well-designed RCTs are
      needed. 

PMID- 24669230
TI  - The Relationship between Stasis-Stagnation Constitution and Peripheral Arterial
      Disease in Patients with Type 2 Diabetes.
AB  - Objectives. In traditional Chinese medicine, Yu-Zhi (YZ, indicating stasis and
      stagnation) constitution describes a body that tends to express abnormal
      circulatory conditions. This study identified the linkage between YZ constitution
      and peripheral arterial disease (PAD) in patients with type 2 diabetes. Methods.
      Patients over 20 years of age who had had type 2 diabetes for 5 years or longer
      were recruited. PAD was diagnosed if the ankle-brachial index score was <=0.9 in
      either leg. Level of YZ constitution was accessed by an YZ Constitution
      Questionnaire. Results. A total of 712 patients (354 men and 358 women) with a
      mean age of 61.5 +/- 10.6 years and diabetes duration of 13.1 +/- 6.7 years were
      recruited. The prevalence of PAD among our patients was 7.2%. Multivariate
      logistic regression revealed significant correlations between PAD and,
      respectively, YZ score, age, diabetes duration, current smoking, and hs-CRP.
      Conclusion. In addition to traditional risk factors, YZ constitution was
      statistically associated with PAD in patients with type 2 diabetes. This result
      invites further research into the effectiveness of traditional Chinese medicine
      to treat YZ constitution. 

PMID- 24669231
TI  - "Nomophobia": impact of cell phone use interfering with symptoms and emotions of
      individuals with panic disorder compared with a control group.
AB  - Panic disorder refers to the frequent and recurring acute attacks of anxiety.
      OBJECTIVE: This study describes the routine use of mobiles phones (MPs) and
      investigates the appearance of possible emotional alterations or symptoms related
      to their use in patients with panic disorder (PD). BACKGROUND: We compared
      patients with PD and agoraphobia being treated at the Panic and Respiration
      Laboratory of The Institute of Psychiatry, Federal University of Rio de Janeiro,
      Brazil, to a control group of healthy volunteers. METHODS: An MP-use
      questionnaire was administered to a consecutive sample of 50 patients and 70
      controls. RESULTS: People with PD showed significant increases in anxiety,
      tachycardia, respiratory alterations, trembling, perspiration, panic, fear and
      depression related to the lack of an MP compared to the control group.
      CONCLUSIONS: Both groups exhibited dependence on and were comforted by having an
      MP; however, people with PD and agoraphobia showed significantly more emotional
      alterations as well as intense physical and psychological symptoms when they were
      apart from or unable to use an MP compared to healthy volunteers.

PMID- 24669232
TI  - Exercise upregulates salivary amylase in humans (Review).
AB  - The secretion of salivary alpha-amylase is influenced by adrenergic regulation of
      the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis; thus,
      exercise affects the levels of salivary alpha-amylase. Granger et al published a
      review in 2007 that focused attention on salivary alpha-amylase. In addition, a
      portable system for monitoring salivary alpha-amylase activity was launched in
      Japan at the end of 2005. The correlation between exercise and salivary alpha
      amylase has since been extensively investigated. The present review summarizes
      relevant studies published in the English and Japanese literature after 2006. A
      search of the PubMed and CiNii databases identified 54 articles, from which 15
      original articles were selected. The findings described in these publications
      indicate that exercise consistently increases mean salivary alpha-amylase
      activities and concentrations, particularly at an intensity of >70% VO2max in
      healthy young individuals. Thus, these studies have confirmed that salivary alpha
      amylase levels markedly increase in response to physical stress. Salivary alpha
      amylase levels may therefore serve as an effective indicator in the non-invasive
      assessment of physical stress.

PMID- 24669233
TI  - Pleural fluid prealbumin and C-reactive protein in the differential diagnosis of
      infectious and malignant pleural effusions.
AB  - Clinical history and physical examination are helpful in indicating the potential
      causes of pleural effusions (PEs). However, the accurate diagnosis and
      establishment of the causes of PE is an ongoing challenge in daily clinical
      practice. The primary aim of this study was to distinguish between infectious PE
      and malignant PE (MPE) by measuring two major acute phase response biomarkers:
      prealbumin (PA) and C-reactive protein (CRP). The study was a prospective trial
      involving 151 patients who were diagnosed with infectious PE or MPE. Patients
      with infectious PE were divided into two subgroups: tuberculous PE (TBPE) and
      parapneumonic PE (PNPE). A further 58 patients with PEs that showed no evidence
      of MPE, TBPE or PNPE were classified as the chronic non-specific PE (NSPE) group.
      Demographic characteristics and pleural fluids of the subjects were collected
      consecutively. The discriminative properties of pleural fluid routine
      biochemistries, and PA and CRP were evaluated. PA, CRP and classical fluid
      parameters were also applied to classify patients with infectious PE and MPE.
      Receiver operating characteristics (ROC) analysis established the cutoffs of PA
      and CRP for discriminating between groups. Pleural fluid PA levels were
      significantly higher in the MPE group (n=47) than in the infectious PE group
      (n=104). Pleural fluid CRP levels were significantly higher in the infectious PE
      group than in the MPE group. Pleural fluid PA levels were identified to be
      moderately negatively correlated with CRP levels in the MPE group, with a
      statistically significant correlation coefficient of -0.352. The ROC curve showed
      that the sensitivity and specificity of PA for the diagnosis of MPE were 0.851
      and 0.548, respectively, at the cutoff of 28.3 mg/l. The area under the curve
      (AUC) was 0.784 (95% CI, 0.707-0.861). Using CRP as a diagnostic parameter
      resulted in an comparable AUC of 0.810 (95% CI, 0.736-0.885), at the cutoff of
      35.2 mg/l. Combinations of PA and CRP resulted in incrementally discriminating
      values for MPE, with a sensitivity of 0.617 and a specificity of 0.903. The
      measurement of PA and CRP levels in pleural fluid may be a useful adjunctive test
      in PE, as a potential differentiator between infectious PE and MPE.

PMID- 24669234
TI  - Connexin expression patterns in diseased human corneas.
AB  - The present study aimed to explore the feasibility of using antisense connexin
      (Cx) treatment to promote corneal wound healing, and to investigate the changes
      of Cx gap junction proteins in terms of mRNA, protein expression and distribution
      in human corneas that were diseased due to various causes. A total of 13 diseased
      corneas were studied, which were obtained from five eyes injured by chemical
      burns, five infected eyes and three eyes with Stevens-Johnson syndrome (SJS)
      affected corneas. Total RNA was extracted from the corneas and processed by qPCR
      with isoform primers to detect the expression of eight Cxs. Flow cytometry was
      adopted to determine the differences in the expression levels of Cx26, Cx31.1 and
      Cx43. Immunofluorescence was employed to show the localization of the three
      aforementioned Cxs. The qPCR results indicated that of the eight Cxs, only Cx26,
      Cx31.1 and Cx43 were upregulated in diseased corneas. Flow cytometry showed that
      all the diseased corneal tissues, with the exception of the SJS-affected corneas,
      showed a significantly higher percentage of cells that expressed Cx26 and Cx31.1
      compared with the percentage in normal corneas (P<0.05). For Cx43, all three
      injured corneal groups showed a significantly higher percentage of cells that
      expressed Cx43 compared with the percentage in normal corneas (P<0.05).
      Immunohistochemical staining showed that the localization of Cx26, Cx31.1 and
      Cx43 differed between normal corneas and diseased corneas. This study elucidated
      the alteration of Cx expression patterns in several corneal diseases. The results
      indicated that Cx26, Cx31.1 and Cx43 are upregulated in chemically burned and
      infected corneas at the mRNA and protein levels, whereas only Cx43 is upregulated
      in SJS-affected corneas.

PMID- 24669235
TI  - A randomized controlled clinical trial of vildagliptin plus metformin combination
      therapy in patients with type II diabetes mellitus.
AB  - The aim of the present study was to assess the efficacy and safety of
      vildagliptin plus metformin combination therapy in patients with type II diabetes
      mellitus. Type II diabetic patients with poor glycemic control following at least
      three months of metformin treatment were selected and randomized into two groups.
      Vildagliptin or placebo was administered with metformin. Body weight, fasting
      blood glucose (FBG), postprandial glucose (PPG), glycated hemoglobin (HbA1c),
      blood lipid and hepatorenal function levels were analyzed in the patients prior
      to and 24-weeks after the trial. FBG, PPG and HbA1c levels of the patients in the
      vildagliptin group significantly decreased following the trial, whereas no
      statistically significant differences were observed in the various indicators of
      the placebo group prior to and following the trial. The FBG, PPG and HbA1c levels
      in the vildagliptin group were significantly lower compared with the placebo
      group 24-weeks after the trial. Comparisons of body weight, blood lipid and
      hepatorenal function between the groups prior to and following the trial
      exhibited no statistically significant differences. Therefore, vildagliptin plus
      metformin combination therapy effectively reduced FBG, PPG and HbA1c levels in
      patients with no risk of weight gain or hepatorenal dysfunction.

PMID- 24669236
TI  - Simultaneous hybrid revascularization for symptomatic lower extremity arterial
      occlusive disease.
AB  - Multilevel revascularization, using a combination of endovascular and open
      (hybrid) surgery, is increasingly being used. Hybrid surgery allows complex
      anatomy to be treated by minimally invasive procedures in medically high risk
      patients. The aim of the present study was to report a novel hybrid surgery for
      lesions in the multilevel lower extremity arteries and to evaluate the clinical
      outcomes. Consecutive patients who presented at a single institution between
      March 2009 and Feburary 2012 were selected for inclusion in the study. The
      patients had disabling claudication or critical limb ischemia and underwent
      treatment for revascularization by open surgery or by a combination of open
      surgery and endovascular procedure. Retrospective analysis was conducted from a
      prospectively collected database. All procedures were performed by a vascular
      surgeon in an operating room. Postoperative surveillance in outpatient clinics
      was conducted at 3 and 6 months and every 6 months thereafter. A total of 76
      patients were included in the study with a mean age of 67.1+/-11.3 years (range,
      42-94 years) and the male to female ratio was 67:9. The most common indication
      for revascularization was Rutherford category IV (resting pain). The immediate
      technical success rate of hybrid surgery was 90.5%, with an overall limb salvage
      rate of 97.4%. The primary patency rates of the hybrid and open groups were 100
      and 90.9%, respectively (P=0.441). Therefore, the results of the present study
      indicate that hybrid surgery is a feasible option for the treatment of multilevel
      peripheral arterial occlusive disease, showing favorable patency and limb salvage
      rates. These observations indicate that femoral endarterectomy plays a vital role
      in hybrid surgery.

PMID- 24669237
TI  - Effects of pioglitazone on nonalcoholic steatohepatitis in a patient with
      anorexia nervosa: A case report.
AB  - Diseases associated with metabolic syndromes are of major concern in developed
      countries. Nonalcoholic steatohepatitis (NASH) is one of the manifestations of
      metabolic syndrome in the liver. Previous studies have shown that NASH is also
      caused by malnutrition. In the present study, a case of malnutrition-associated
      NASH in a 66-year-old female with anorexia nervosa is reported. The patient had a
      body mass index (BMI) of only 11.1 kg/m2 and serum alanine aminotransferase
      levels of 1,495 IU/l. Steatohepatitis with fibrosis was confirmed by percutaneous
      liver needle biopsy. Total parenteral nutrition was conducted at first, followed
      by the administration of Stronger Neo-Minophagen C (a glycyrrhizin-containing
      preparation), ursodeoxycholic acid and prednisolone. The abnormal elevation of
      aminotransferase levels of the patient was prolonged and total bilirubin levels
      increased. Pioglitazone (15 mg/day), which has been identified to be effective
      for nonalcoholic steatohepatitis, was then administered. This resulted in marked
      reductions in aminotransferase and bilirubin levels within three months.
      Histological improvement of the liver was also confirmed by percutaneous liver
      needle biopsy after one year. The observations in the present case suggest that
      pioglitazone may be useful for the treatment of malnutrition-associated NASH.

PMID- 24669238
TI  - Needle-knife therapy improves the clinical symptoms of knee osteoarthritis by
      inhibiting the expression of inflammatory cytokines.
AB  - Knee osteoarthritis (KOA) is a degenerative joint disease that occurs mainly in
      the elderly population. However, there are currently no effective treatments for
      treating this condition. In this study, the efficacy of needle-knife therapy, a
      technique of traditional Chinese medicine that has been widely used to treat KOA
      was investigated. Patients (n=170) with KOA were randomly divided for needle
      knife therapy (treatment group) and acupuncture therapy (control group). Outcome
      evaluation included stiffness, pain, physiological function, overall changes,
      total symptom score, clinical curative effects and the concentrations of
      interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the
      synovial fluid. The trial was completed in 151 patients (233 knees) from a total
      of 170 patients (264 knees); the treatment group comprised 76 patients (117
      knees) who completed the trial and 9 patients (14 knees) who were removed from
      the study, and the control group comprised 75 patients (116 knees) who completed
      the trial and 10 patients (17 knees) who were removed from the study. The symptom
      scores of KOA in stages I-IV were reduced significantly in the treatment group
      and those of stages I-III were decreased significantly in the control group. The
      effective rate of the KOA therapy in the patients of stages III and IV in the
      treatment group was significantly higher than that in the control group. After
      treatment, the decrements of IL-1beta, IL-6 and TNF-alpha in the treatment group
      were greater than those in the control group. These results showed that the use
      of needle-knife therapy to treat KOA effectively improved the clinical symptoms
      by inhibiting the expression of inflammatory cytokines.

PMID- 24669239
TI  - Construction and expression of a human/mouse chimeric CD19 monoclonal antibody:
      Successful modification of a murine IgM to a chimeric IgG.
AB  - CD19 is a specific surface marker of B cells. A murine IgM-subtype antibody, 2E8,
      was generated previously and assigned to the CD19 category by the 6th
      International Workshop and Conference on Human Leukocyte Differentiation Antigens
      in 1996. In the present study, the 2E8 Fv gene was inserted into a baculovirus
      shuttle vector and novel protein was expressed in an IgG1 form in the Sf9 insect
      cell line. VH2E8 and VL2E8 genes were cloned and inserted into the baculovirus
      shuttle vector pAc-kappa-CH3 to form pAc-kappa-CH3-VH2E8-VL2E8. Sf9 cells were
      then transfected with the reconstructed baculovirus shuttle vector. Novel protein
      expressed by the Sf9 cells was identified by immunofluorescence and western blot
      analysis, while activity levels were analyzed by flow cytometry (FCM). Sequencing
      demonstrated that the VH2E8 and VL2E8 fragments were inserted into pAc-kappa-CH3
      correctly. The immunofluorescence, western blot analysis and FCM results
      indicated that active recombinant antibody was expressed in the cytoplasm of Sf9
      cells, but not in the culture supernatant. Thus, functional recombinant antibody
      was expressed successfully in the cytoplasm of Sf9 cells, but was not secreted
      into the culture supernatant. Therefore, the present study demonstrates that it
      is possible to modify mouse IgM to mouse-human chimeric IgG1 while retaining
      reasonable biological activity.

PMID- 24669240
TI  - Gefitinib-induced interstitial pneumonia: A case report and review of the
      literature.
AB  - The aim of this study was to explore the clinical characteristics of and
      treatment strategies for interstitial pneumonia induced by gefitinib in patients
      with advanced non-small cell lung cancer (NSCLC). The detailed clinical data of
      one patient with NSCLC and gefitinib-induced interstitial pneumonia were compiled
      and a review of relevant previous studies was performed. Based on this case
      report and the review, the clinical characteristics, mechanisms and treatment
      strategies of this rare disease were analyzed. The analyses showed that older,
      male patients with a long smoking history, high smoking index and adenocarcinoma
      (particularly bronchoalveolar carcinoma) were more likely to suffer from
      interstitial pneumonia while taking gefitinib. The onset time of interstitial
      pneumonia was 1-2 months subsequent to gefitinib administration. The clinical
      manifestations included chest tightness, shortness of breath, progressive
      dyspnea, severe hypoxemia and respiratory failure. Diffuse infiltration and
      alveolar interstitial shadows were observed on the chest tomography scan. In such
      circumstances, a timely judgment is required, in addition to the withdrawal of
      gefitinib treatment and the administration of high-dose glucocorticoids, as well
      as oxygen inhalation and anti-infective therapies, in order to relieve the
      symptoms. In conclusion, following the onset of gefitinib-induced interstitial
      pneumonia, the discontinuation of gefitinib is likely to alleviate the suffering
      of the majority of patients. Early interstitial pneumonia is not an absolute
      index for the permanent discontinuation of gefitinib treatment. It is necessary
      to comprehensively consider the benefits and hazards of gefitinib for the
      patients.

PMID- 24669241
TI  - Correlation analysis between eGFRcys and SXscore in patients with diabetes.
AB  - The aim of the present study was to explore the association between the cystatin
      C-based estimated glomerular filtration rate (eGFRcys) and the SYNTAX score
      (SXscore) in patients with diabetes. To the best of our knowledge, this
      correlation has not been reported previously. The eGFRcys and SXscore from 612
      consecutive patients with diabetes were retrospectively included in this study.
      The patients were angiographically diagnosed with coronary artery disease (CAD)
      between July 2010 and March 2012 at the Department of Endocrinology. The SXscore
      was calculated using a previously described SXscore algorithm. Pearson
      correlations were used to analyze the correlation between eGFRcys and SXscore.
      Patients with renal dysfunction were older, more often female and more likely to
      have a history of hypertension when compared with those with normal renal
      function. The eGFRcys values were significantly lower and the cystatin C levels
      were significantly higher in the highest SXscore group than those in other groups
      (P<0.001). Correlation analysis indicated that eGFRcys was negatively correlated
      with the SXscore (r=-0.7918, P<0.001). In addition, a significantly positive
      correlation was identified between levels of cystatin C and the SXscore
      (r=0.8891, P<0.001). In conclusion, eGFRcys is an independent predictor of
      SXscore in patients with diabetes. The eGFRcys-estimating method may be
      considered important in the assessment of the SXscore in patients with diabetes.

PMID- 24669242
TI  - Diagnostic value of Flash dual-source CT coronary artery imaging combined with
      dual-energy myocardial perfusion imaging for coronary heart disease.
AB  - The present study aimed to investigate the diagnostic value of Flash dual-source
      CT coronary angiography (DS-CTA) combined with dual-energy myocardial perfusion
      imaging (DS-CTP) for coronary heart disease (CHD), as a single-stage examination.
      A total of 60 patients with CHD underwent DS-CT examination, as well as coronary
      angiography (CAG), as the reference standard. The patients were divided into <50%
      and >=50% stenosis groups based on their coronary angiograms. The sensitivity,
      specificity, positive predictive value, negative predictive value and accuracy of
      the method for diagnosing stenosis of >=50% were evaluated via DS-CTA combined
      with DS-CTP. Of the 60 patients, 59 showed satisfactory results that conformed to
      the diagnostic requirements. Using CAG as the reference standard, the
      sensitivity, specificity and positive and negative predictive values of the Flash
      DS-CT results in the >=50% vascular stenosis group were 83.7, 92.7, 88.9 and
      89.1%, respectively. The respective values for DS-CTA combined with DS-CTP for
      diagnosing CHD were 94.2, 91.1, 88.0 and 95.8%. Therefore, the results obtained
      indicate that DS-CTA combined with DS-CTP has a high diagnostic value for CHD. DS
      CT is advantageous for diagnosing and prognosticating CHD.

PMID- 24669243
TI  - Evaluation of a robot-assisted video-assisted thoracoscopic surgery programme.
AB  - At present, there is increasing interest in surgical procedures using a robot
      assisted device. The aim of this study was to investigate whether robot-assisted
      video-assisted thoracoscopic surgery (VATS) was more effective than conventional
      VATS. A total of 64 VATS lobectomies in Papworth Hospital (Cambridge, UK) were
      included in the study. In 34 cases the lobectomies were performed using
      conventional VATS (CV group), while in the remaining 30 cases the lobectomies
      were performed using robot-assisted VATS (Robotic group). In the robot-assisted
      VATS, FreeHand(r), a thoracoscopic camera controller produced by Freehand 2010
      Ltd. (Eastleigh, UK), was used. The duration of the thoracoscopic surgery in the
      Robotic group was 145.50+/-10.43 min, whereas in the CV group the duration was
      162.79+/-9.40 min. The surgery duration in the Robotic group was 10.62% shorter
      than that in the CV group (P<0.05). The rates of bleeding, pulmonary infection,
      arrhythmia and prolonged air leak (>=5 days) in the Robotic group were 0, 3.33,
      26.67 and 13.33%, respectively, while the corresponding rates in the CV group
      were 2.94, 5.88, 20.59 and 17.65%, respectively. No significant differences were
      identified in the postoperative complication rates between the two groups
      (P>=0.05). There was no perioperative mortality in the study. Compared with
      conventional VATS, FreeHand-assisted VATS provides a similar rate of
      postoperative complications and a reduced surgery duration, and may be beneficial
      for the recovery of the patients following VATS.

PMID- 24669244
TI  - Effect of voice training in the voice rehabilitation of patients with vocal cord
      polyps after surgery.
AB  - The objective of the present study was to determine the effect of voice training
      on the vocal rehabilitation of patients with vocal cords polyps following
      phonomicrosurgery. A total of 60 cases of vocal cord polyps treated by laser
      phonomicrosurgery were randomly divided into training and control groups with 30
      cases in each group. The patients were treated with laser phonomicrosurgery,
      routine postoperative treatment and nursing. The training group were additionally
      treated with vocal training, including relaxation training, breathing training,
      basic pronunciation training, chewing voice training and tone sandhi
      pronunciation training, and attention was paid to the training steps. Subjective
      and objective voice evaluations of the two groups were compared three months
      after the surgery and the differences between groups were statistically
      significant (P<0.05). Voice training may significantly improve the postoperative
      voice quality of patients with vocal cord polyps and support rehabilitation.

PMID- 24669245
TI  - Diagnostic value of serum leptin and a promising novel diagnostic model for
      sepsis.
AB  - Diagnosis of sepsis in critically ill patients is important to reduce morbidity
      and mortality. The present study was conducted to determine the role of serum
      leptin in the early diagnosis of sepsis and to establish a diagnostic model for
      sepsis. A retrospective study was conducted of 331 patients from an intensive
      care unit. All patients underwent consistent blood collection at 6:00 a.m. every
      morning after fasting. Serum leptin concentrations and additional markers of
      sepsis were compared between the sepsis group (n=128) and the non-sepsis group
      (n=203). Septic patients displayed significantly higher leptin serum
      concentrations compared with those of the non-sepsis group (mean concentration,
      11.67 versus 4.824 mg/dl; P<0.001). The leptin levels in male patients were
      higher than those in female patients, particularly in the sepsis group. The
      accuracy of serum leptin levels in distinguishing septic patients from non-septic
      patients was 76%, and the area under the receiver operating characteristic (ROC)
      curve of serum leptin was <=0.8. Additional markers of inflammation in the sepsis
      group were also significantly higher than those in the non-sepsis group. Positive
      correlations were identified between leptin and body temperature, heart rate and
      creatinine levels. Therefore, a prognostic model comprising a combination of
      leptin with temperature, platelet count, white blood cell count and heart rate
      was evaluated as an effective logistic regression model for the diagnosis of
      sepsis. The logistic regression output cut-off value was 0.46 and the area under
      the ROC curve was 0.953 (P<0.0001). It may be concluded that leptin is a valuable
      marker in the diagnosis of sepsis and the proposed prognostic model is an
      effective logistic regression model for the diagnosis of sepsis. The prognostic
      model is able to aid the differentiation of septic patients from non-septic
      patients.

PMID- 24669246
TI  - In vitro anti-MRSA activity of carvone with gentamicin.
AB  - Carvone is one of the naturally occurring monoterpenes, the largest class of
      secondary metabolites in plants, and exists in two enantiomers, R-carvone (R-car)
      and S-car. The objective of this study was to investigate the antimicrobial
      activity of R-car and S-car with gentamicin (GET) against methicillin-resistant
      Staphylococcus aureus (MRSA). MRSA is a major human pathogen that causes serious
      problems, including hospital-acquired pneumonia, abscesses and surgical wound
      infections. Nosocomial MRSA infections often exhibit multidrug resistance. In the
      present study, antimicrobial susceptibility testing was performed with R-car, S
      car and GET using the broth microdilution method. Minimal inhibitory
      concentration values for R- and S-car against six different strains of S. aureus
      ranged between 500 and 1,000 MUg/ml. Anti-MRSA activity was evaluated using the
      checkerboard and time-kill assays to investigate the potential synergistic
      effects of different combinations of the carvone enantiomers and GET. R-car plus
      S-car, R-car plus GET and S-car plus GET exhibited significant synergistic
      activity against MRSA. These findings suggest that the single-agent anti-MRSA
      activities of R-car, S-car and GET are effectively increased through combination
      therapy. This study showed that carvone may be a potential adjuvant antimicrobial
      agent.

PMID- 24669247
TI  - Therapeutic efficacy comparison of radiofrequency ablation in hepatocellular
      carcinoma and metastatic liver cancer.
AB  - The aim of this study was to evaluate the effect of radiofrequency ablation (RFA)
      on malignant hepatic tumors and compare its therapeutic efficacy in
      hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). A total of 56
      patients with malignant hepatic tumors (34 patients with HCC and 22 patients with
      MLC) underwent RFA treatment. Two weeks following the RFA treatment, contrast
      enhanced abdominal computed tomography scans were used to investigate whether the
      ablation of the tumors was complete. The patients were followed up for a period
      ranging from 1 to 93 months, to compare recurrence rates, distant recurrence
      rates and survival rates. The HCC group exhibited an initial complete ablation
      rate of 94.1% compared with 95.4% for the MLC group; the difference in ablation
      rates was not identified to be statistically significant. The recurrence and
      distant recurrence rates were 14.7% and 11.8%, respectively, for the HCC group
      and 9.1% and 36.4%, respectively, for the MLC group. The 1-, 3- and 5-year
      survival rates of the patients with HCC were 86.2, 71.4 and 60.0%, respectively,
      whereas those for the patients with MLC were 73.9%, 45.4% and 37.5%,
      respectively. The survival rates of the two groups were identified to be
      significantly different (P=0.002). RFA treatment was therefore shown to be
      effective in treating small (<5 cm) malignancies, which is clinically
      significant.

PMID- 24669248
TI  - Differential expression of miRNA in rat myocardial tissues under psychological
      and physical stress.
AB  - In the current study, microRNA (miRNA) microarrays were used to detect
      differentially expressed miRNAs in the myocardial tissues of rat models under
      stress, to screen target miRNA candidates for miRNA therapy of stress-induced
      myocardial injury. Rats were bound and suspended in order to induce acute stress
      (AS) and chronic stress (CS) models. miRNA microarrays were used to detect
      differentially expressed miRNA in the myocardial tissues of the stressed and
      control groups. In comparison to the normal control, there were 68 differentially
      expressed miRNAs in the AS model, of which 32 were upregulated and 36 were
      downregulated. There were 55 differentially expressed miRNAs in the CS model, of
      which 20 were upregulated and 35 were downregulated. Of the 123 miRNAs, 15 miRNAs
      were differentially expressed between the AS and CS groups, of which four were
      significantly upregulated (rno-miR-296, rno-miR-141, rno-miR-382 and rno-miR-219
      5p) and 11 were downregulated (significantly downregulated, rno-miR-135a and rno
      miR-466b). The stress of being bound and suspended induces myocardial injury in
      the rats. Myocardial injury may cause the differential expression of certain
      miRNAs. Psychological stress may lead to the significant upregulation of rno-miR
      296, rno-miR-141, rno-miR-382 and rno-miR-219-5p in addition to the significant
      downregulation of miR-135a and miR-466b.

PMID- 24669249
TI  - A modified HPLC method improves the simultaneous determination of plasma
      kynurenine and tryptophan concentrations in patients following maintenance
      hemodialysis.
AB  - The ratio between plasma kynurenine (Kyn) and tryptophan (Trp) serves as a marker
      of indoleamine 2,3-dioxygenase, a critical immunomodulatory molecule.
      Simultaneous detection of the two markers may be performed using high-pressure
      liquid chromatography (HPLC). However, for uremic patients, the conventional
      detection method may be affected by a range of accumulated toxins. The current
      study aimed to establish a method for the simultaneous measurement of Kyn and Trp
      in patients following maintenance hemodialysis via HPLC-ultraviolet detection.
      The procedure involved the use of a SinoChrom ODS-BP C18 column (4.6*150 mm;
      inner diameter, 4.5 MUm) and a mobile phase of 15 mmol/l sodium acetate acetic
      acid solution (containing 5% acetonitrile, pH 4.8). The modified method was
      verified using plasma samples from 10 healthy controls and 91 maintenance
      hemodialysis patients. The results demonstrated that the modified method was
      successful in simultaneously detecting the concentrations of Trp and Kyn in the
      healthy controls and maintenance hemodialysis patients. The method is simple,
      fast, accurate and suitable for clinical and research purposes in maintenance
      hemodialysis patients.

PMID- 24669250
TI  - Endostar combined with radiotherapy increases radiation sensitivity by decreasing
      the expression of TGF-beta1, HIF-1alpha and bFGF.
AB  - The aim of the present study was to determine how Endostar inhibits tumor
      angiogenesis and increases radiation sensitivity when combined with radiotherapy.
      In vitro studies were conducted to analyze the expression levels of transforming
      growth factor-beta1 (TGF-beta1), hypoxia-inducible factor 1 (HIF-1alpha) and
      basic fibroblast growth factor (bFGF) in lung adenocarcinoma A549 cells, using
      the antiangiogenesis drug Endostar combined with radiotherapy. In addition, lung
      adenocarcinoma A549 cell apoptosis was detected via Hoechst staining. The
      combination of Endostar with radiotherapy was investigated and the results
      indicated that this combination significantly inhibited tumor cell proliferation
      and TGF-beta1, HIF-1alpha and bFGF expression. Changes in gene expression were
      found to promote apoptosis, thus, enhancing the inhibition of tumor angiogenesis
      and ultimately inhibiting tumor cell growth, invasion and metastasis.

PMID- 24669251
TI  - Value of multi-detector computed tomography angiography in predicting acute
      cardiac events in patients with type 2 diabetes.
AB  - The aim of the present study was to investigate the predictive value of multi
      detector computed tomography angiography (MDCTA) on acute coronary artery events
      in patients with type 2 diabetes mellitus (T2DM). MDCTA was performed in 150
      patients with T2DM (males, 74; mean age, 66+/-6.7 years for all patients) that
      had experienced atypical chest pains. After a follow-up period of at least 2
      years, 55 patients were excluded from the study as they did not exhibit any
      coronary events. The remaining 95 patients were divided into the study group
      (n=28), that had experienced an acute coronary event such as acute coronary
      syndrome, or the control group (n=67) that had stable angina. There were no
      statistically significant differences in the degree of coronary artery lumen
      stenosis between the study and control groups (P=0.380). The proportion of
      calcified plaques in the study group was significantly lower compared with the
      control group (13.6 vs. 53.2%; P<0.001), while the proportion of soft plaques in
      the study group was significantly higher compared with the control group (37 vs.
      9.3%; P<0.001). Type III plaques showed a sensitivity of 76.2% and a negative
      predictive value of 64.5% for acute coronary events. By contrast, type IV plaques
      had a sensitivity of 52.6% and a positive predictive value of 63% for chronic
      coronary events. Therefore, the results of the present study indicate that MDCTA
      may be used as a noninvasive modality for evaluating and predicting vulnerable
      coronary atherosclerosis plaques in patients with T2DM.

PMID- 24669252
TI  - Effects of resveratrol on cell growth and prolactin synthesis in GH3 cells.
AB  - Resveratrol (RE), a phytoestrogen, has antiestrogenic properties. Estrogen plays
      a key role in the development and progression of pituitary prolactinoma.
      Moreover, RE is a potent cancer chemopreventive agent that inhibits the
      initiation, promotion and progression of carcinogenesis. The present study
      investigated the antitumor effects of RE on GH3 pituitary tumor cells. A
      concentration- and treatment duration-dependent biphasic effect of RE on the
      proliferation of the GH3 cells was demonstrated. After three days of treatment,
      RE stimulated proliferation at low concentrations and inhibited proliferation at
      high concentrations. However, when the treatment duration was reduced to 6 h, RE
      inhibited proliferation in a concentration-dependent manner. In addition, RE
      induced apoptosis with the activation of caspase-3 and -8, and decreased the
      percentage of prolactin (PRL)-immunopositive GH3 cells. Furthermore, RE
      suppressed expression of the PRL gene and inhibited the cell proliferation and
      PRL synthesis induced by 17beta-estradiol (E2). In GH3 cells, the proliferation
      response exhibited higher sensitivity to E2 compared with the PRL response; by
      contrast, the PRL response was more sensitive to RE than the proliferation
      response was. These results indicate that RE, an antiestrogenic compound, exerts
      its antitumor effect on GH3 cells through the suppression of GH3 cell growth and
      through the inhibition of PRL synthesis. The RE-induced cell apoptosis was shown
      to be caspase-dependent. Therefore, the present study provides support for the
      use of RE in the chemoprevention and chemotherapy of pituitary prolactinoma.

PMID- 24669253
TI  - Risk factors for intestinal metaplasia in concomitant gastric and duodenal ulcer
      disease.
AB  - The aim of this study was to estimate the prevalence and risk factors of
      intestinal metaplasia (IM) in concomitant gastric and duodenal ulcer (CGDU)
      disease by retrospectively reviewing consecutive patients who had undergone
      esophagogastroduodenal endoscopy. Patients who received the endoscopic diagnosis
      of CGDU disease were selected for analysis and the recorded demographic,
      endoscopic, clinical and outcome data, including data on the development of IM,
      were extracted. Associations of the various parameters with IM were estimated by
      logistic regression analysis and described by the odds ratio (OR) with a 95%
      confidence interval (CI). Among the total 204,073 consecutive patients screened,
      2,397 (1.2%) were diagnosed with CGDU disease. Following application of the
      exclusion criteria, a total of 2,149 cases were included in the study. The IM
      prevalence was 8.4%, represented by 153 mild cases, 26 moderate cases and one
      severe case. Multivariate analysis identified age >=50 years (OR=2.606, 95%
      CI=1.889-3.597, chi2=34.000, P<0.001), ulcer at the gastric incisura (OR=2.644,
      95% CI=1.926-3.630, chi2=36.142, P<0.001) and Helicobacter pylori (H. pylori)
      infection (OR=2.338, 95% CI=1.573-3.474, chi2=17.648, P<0.001) as independent
      risk factors for the development of IM. In addition, the moderate and severe IM
      grades were more frequently detected in males than in females (18.8% vs. 5.8%;
      OR=3.769, 95% CI=1.083-13.121, chi2=4.887, P=0.036). IM in patients with CGDU
      disease is not uncommon. CGDU patients with ongoing H. pylori infection, gastric
      incisura involvement, older age and/or male gender may be at a higher risk of IM.

PMID- 24669254
TI  - M1/M2 macrophages and associated mechanisms in congenital bicuspid aortic valve
      stenosis.
AB  - The aim of this study was to observe macrophage infiltration in congenital
      bicuspid aortic valve (CBAV) stenosis. M1/M2 macrophage distribution,
      inflammatory cytokine expression and the role of M1 macrophages during CBAV
      stenosis were also explored. The experimental and control groups comprised 30
      severely stenotic CBAVs and 30 severely stenotic tricuspid aortic valves (TAVs),
      respectively. Histological and morphological changes were assessed using
      hematoxylin-eosin (HE) staining and mRNA levels of vascular endothelial growth
      factor (VEGF) were examined using the quantitative polymerase chain reaction.
      Nonspecific, M1 and M2 macrophages were monitored using cluster of
      differentiation (CD)68, inducible nitric oxide synthase (iNOS) and CD163
      staining, respectively. Endothelial nitric oxide synthase (eNOS), interleukin
      (IL)-10, arginase (Arg)-1 and macrophage colony-stimulating factor (M-CSF) were
      also examined using immunohistochemical staining. Of note, HE staining revealed a
      higher cell density and neovascularization was more common in CBAVs than TAVs. At
      the mRNA level, VEGF expression was two-fold higher in CBAVs relative to that in
      TAVs (P=0.02). Furthermore, CD68 and iNOS were significantly higher in CBAVs
      compared with TAVs (P=0.029 and 0.021, respectively), while CD163 expression was
      lower in CBAVs (P=0.033). In addition, eNOS expression was higher and Arg-1, IL
      10 and M-CSF expression were lower in CBAVs compared with TAVs (all P<0.0001).
      The present study suggested that CBAVs are associated with a higher total and M1
      macrophage density and a lower M2 macrophage density than TAVs, and that M1
      macrophage infiltration may contribute to calcification of CBAVs.

PMID- 24669255
TI  - Evaluation of hypokalemia and potassium supplementation during administration of
      liposomal-amphotericin B.
AB  - Patients prescribed liposomal-amphotericin B (L-AMB) frequently require
      supplemental potassium to prevent hypokalemia. The aim of this retrospective
      study was to examine the appropriate potassium supplementation conditions to
      treat hypokalemia induced by L-AMB. The subjects were 100 hematological patients
      who received L-AMB for the first time between April 2012 and March 2013. A total
      of seven patients were excluded. Of the remaining 93 patients, 48 (51.6%) were
      assigned to the group receiving supplemental potassium (supplementation group),
      and 45 (48.4%) were assigned to the group without potassium supplementation (non
      supplementation group). Hypokalemia greater than grade 3 was exhibited by 50 of
      the 93 (53.8%) patients. Multivariate analysis revealed that the minimum serum
      potassium levels during L-AMB administration (<=2.98 mEq/l) were an independent
      factor significantly contributing to the effectiveness of potassium
      supplementation [odds ratio (OR), 3.62; 95% confidence interval (CI), 1.44-9.59;
      P<0.01]. In addition, multivariate analysis revealed that the serum potassium
      levels (>=2.83 mEq/l) prior to the potassium supplementation were an independent
      factor significantly contributing to the development of proper potassium
      supplementation (OR, 14.21; 95% CI, 1.95-310.72; P=0.02), and no significant
      difference was observed in the dosage of the potassium supplementation
      administered to the patients who recovered from hypokalemia and those who did
      not. In conclusion, it is necessary to begin potassium supplementation prior to
      the reduction of the serum potassium levels to <2.83 mEq/l. Potassium
      supplementation at an early stage of L-AMB treatment is important to prevent
      severe electrolyte abnormalities.

PMID- 24669256
TI  - Effects of three blood purification methods on serum fibroblast growth factor-23
      clearance in patients with hyperphosphatemia undergoing maintenance hemodialysis.
AB  - The aim of the present study was to investigate the effects of three blood
      purification methods on fibroblast growth factor-23 (FGF-23) clearance in
      patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). In
      addition, the correlation between serum FGF-23 and phosphorus (Pi) levels and the
      clinical implications were identified. Sixty-five MHD patients with
      hyperphosphatemia were randomly divided into three groups: Hemodialysis, HD
      (n=23); hemodiafiltration, HDF (n=21); and hemodialysis+hemoperfusion, HD+HP
      (n=21) groups. Serum Pi, FGF-23, blood urea nitrogen, serum creatinine and
      associated bio-marker levels were measured prior to and following treatment. The
      expression level of serum FGF-23 was observed to be positively correlated with Pi
      (r=0.45, P<0.01). The three blood purification methods that were adopted for the
      present study exhibited significant and effective clearance of serum Pi (P<0.05).
      The post-treatment serum FGF-23 levels were significantly decreased in the HDF
      and HD+HP groups (P<0.05). Therefore, HDF may be an effective method for clearing
      serum FGF-23 in MHD patients exhibiting hyperphosphatemia.

PMID- 24669257
TI  - Proximal 10q duplication in a child with severe central hypotonia characterized
      by array-comparative genomic hybridization: A case report and review of the
      literature.
AB  - Proximal 10q duplication is a well-defined but rare genetic syndrome. Duplication
      of proximal segments of the long arm of chromosome 10 results in a pattern of
      malformations, which are distinct from those of the more common distal 10q
      trisomy syndrome. The present study describes the case of a boy with phenotypic
      abnormalities (severe central hypotonia, mild ataxia, moderate developmental
      delay and mild dysmorphic features), due to duplication of chromosome region,
      10q11.21->q11.22, which was characterized by the array-comparative genomic
      hybridization (CGH) technique. The phenotypic findings were compared with those
      in eight additional similar published cases. Major similarities have emerged,
      suggesting a likely minimal critical region. However, only detailed
      characterization of additional cases may provide firm conclusions.

PMID- 24669258
TI  - Construction of functional tissue-engineered bone using cell sheet technology in
      a canine model.
AB  - The aim of the present study was to construct functional tissue-engineered bone
      with cell sheet technology and compare the efficacy of this method with that of
      traditional bone tissue engineering techniques. Canine bone mesenchymal stem
      cells (BMSCs) were isolated using density gradient centrifugation and then
      cultured. The BMSCs were induced to differentiate into osteoblasts and cultured
      in temperature-responsive culture dishes. The BMSCs detached automatically from
      the temperature-responsive culture dishes when the temperature was reduced to 20
      degrees C, forming an intact cell sheet. Demineralized bone matrix (DBM) and
      platelet-rich plasma (PRP) were prepared and used to construct a DBM/PRP/BMSC
      cell sheet/BMSC complex, which was implanted under the left latissimus dorsi
      muscle in a dog model. A DBM/PRP/BMSC complex was used as a control and implanted
      under the right latissimus dorsi muscle in the dog model. Immunoblot assays were
      performed to detect the levels of growth factors. Osteogenesis was observed to be
      induced significantly more effectively in the DBM/PRP/BMSC cell sheet/BMSC
      implants than in the DBM/PRP/BMSC implants. Immunoblot assay results indicated
      that the levels of the growth factors platelet-derived growth factor (PDGF) and
      vascular endothelial growth factor (VEGF) in the experimental group were 3.2- and
      2.5-fold higher compared with those in the control group, respectively. These
      results indicated that the BMSC cell sheets were functional and more effective
      than the control cell complex. Therefore, cell sheet technology may be used for
      the effective construction of functional tissue-engineered bone with ideal
      properties.

PMID- 24669259
TI  - Effects of bone cement on intervertebral disc degeneration.
AB  - Percutaneous vertebroplasty (PVP) is popular for the treatment of intractable
      pain due to vertebral collapse from various lesions, intervertebral disk leakage
      of cement is a frequent complication. The aim of this study was to determine
      whether bone cement causes disc degeneration, and to evaluate the degree of
      intervertebral disc degeneration (IDD) according to the time period following
      cement injection, and the type and volume of cement injected. Sixteen dogs were
      randomly divided into two groups that were sacrificed at 12 or 24 weeks following
      cement injection. Five intervertebral discs in each dog were studied, including
      one control untreated disc and four discs randomly injected with
      polymethylmethacrylate (PMMA) or calcium phosphate cement (CPC) in two
      quantities. Radiographic and magnetic resonance imaging (MRI) studies were
      performed prior to animal sacrifice. T2-weighted mid-sagittal images of the discs
      were qualitatively analyzed for evidence of degeneration by calculating the MRI
      index, and all harvested discs were studied histopathologically. IDD was not
      evident in control discs. Univariate analysis revealed significant differences in
      the MRI index and the histological grade of disc degeneration in terms of the
      time period following cement injection, as well as the type and volume of cement
      injected. Result indicate that direct contact with PMMA and CPC can lead to IDD.
      However, IDD induced by PMMA was more severe than that induced by CPC. The extent
      of IDD was found to correlate with the time period post-cement injection and the
      volume of cement injected into the disc. PMMA and CPC may lead to intervertebral
      disc degeneration. Intervertebral disc degeneration induced by PMMA is more
      serious than that of CPC. The degree of intervertebral disc degeneration is
      correlative to the time after operation and the doses of bone cement.

PMID- 24669260
TI  - Correlation between single nucleotide polymorphisms of the ACTA2 gene and
      coronary artery stenosis in patients with type 2 diabetes mellitus.
AB  - This study aimed to analyze the correlation between single nucleotide
      polymorphisms (SNPs) of the actin, aortic smooth muscle (ACTA2) gene and coronary
      artery stenosis in patients with type 2 diabetes mellitus (T2DM). Eight SNPs from
      the promoter region of the ACTA2 gene were screened. Patients with T2DM (n=251)
      were divided into two groups, those with severe coronary stenosis (SCS+ group;
      n=168) and those without severe coronary stenosis (SCS- group; n=83). Patients
      were also divided according to lesion branching into those whose lesions involved
      less than three branches (LCA- group) and those whose lesions involved at least
      three branches (LCA+ group). The clinical and laboratory data of the patients
      were collected, and the genotyping of eight SNPs was conducted followed by
      statistical analysis. Of the eight SNPs, only the rs1324551 SNP was identified to
      be significantly different between the SCS+ and SCS- groups (P<0.05). The
      frequency of the rs1324551 G allele and GG genotype in the SCS+ group was
      significantly higher than that of the SCS- group (P=0.044 and P=0.001,
      respectively). No significant difference was observed between the LCA- and LCA+
      groups. Following the deduction of age, gender and traditional risk factors, the
      odds ratios of the GG genotype in additive and recessive models were 2.93 [95%
      confidence interval (CI), 1.05-8.19; P=0.04] and 2.34 (95% CI, 1.09-5.02;
      P=0.03), respectively, and this relevancy was represented only in patients with
      low insulin levels. Age and smoking were also found to increase the risk of
      coronary artery lesions. In conclusion, the rs1324551 SNP in the promoter region
      of the ACTA2 gene was identified to be independently correlated with the degree
      of coronary artery stenosis in patients with T2DM and plasma insulin may inhibit
      coronary artery stenosis during the pathogenic process.

PMID- 24669261
TI  - Short-course bortezomib-based retreatment for patients with multiple myeloma who
      had received bortezomib-thalidomide-dexamethasone (VTD) as an initial therapy: A
      single-center case series.
AB  - Studies have shown that the bortezomib-based retreatment of patients with
      multiple myeloma (MM) may prolong control of the disease. The optimal duration of
      bortezomib-based retreatment in relapsed or refractory MM is unknown. The present
      retrospective study evaluated the efficacy and safety of short-course bortezomib
      based retreatment in patients who had received bortezomib-thalidomide
      dexamethasone (VTD) treatment for the initial therapy of newly diagnosed MM. The
      clinical records of 20 patients who had received short-course bortezomib-based
      retreatment in a single center were reviewed. Patients received a median of two
      cycles of bortezomib as the retreatment and the overall response rate was 90%.
      Six (30%), eight (40%) and four (20%) patients achieved a complete response (CR),
      a very good partial response and a partial response, respectively. Of the 10
      patients who had achieved a CR during the initial VTD treatment, six experienced
      a repeat CR during the retreatment. The median duration of the response was nine
      months and the median time to progression was 10.5 months. The most common grade
      I and II adverse events were thrombocytopenia and neutropenia. The short-course
      bortezomib-based retreatment was well tolerated and the favorable response rates
      observed suggest that it may be an effective and convenient treatment option for
      certain patients, particularly elderly patients.

PMID- 24669262
TI  - Splenic metastasis of ovarian clear cell adenocarcinoma: A case report and review
      of the literature.
AB  - Splenic metastasis of ovarian cancer appears to be more common in serous
      cystadenocarcinomas. Splenic metastasis usually occurs postoperatively and
      simultaneously with dissemination to the greater omentum and pelvic cavity.
      Compared with other ovarian cancer subtypes, ovarian clear cell adenocarcinoma
      (OCCA) is rare, accounting for <5% of all ovarian malignancies. OCCA has a
      distinct histological type with poor prognosis and resistance to platinum-based
      chemotherapy. In the present study, a case of isolated splenic metastasis of OCCA
      was reported. A 53-year-old female presented with a mass in the left upper
      quadrant without any other clinical manifestations. Subsequent abdominal and
      pelvic computed tomography scans revealed multiple mixed cystic-solid lesions,
      potentially predicting ovarian malignancy. Pathological tests following ovarian
      cytoreductive surgery revealed primary OCCA with metastases to the spleen. The
      current study also reviewed recently published literature on splenic metastasis
      of ovarian carcinoma and demonstrated that the reported case was a rare case of
      isolated splenic metastasis of OCCA.

PMID- 24669263
TI  - Prevention of amiodarone-induced cardiac toxicity in male BALB/c mice by a
      nutrient mixture.
AB  - Amiodarone (Amio), a potent anti-arrhythmic drug, is associated with life
      threatening pulmonary toxicity involving fibroses and inflammation. A unique
      nutrient mixture (NM) consisting of lysine, proline, ascorbic acid, N-acetyl
      cysteine and green tea extract has previously been shown to exhibit a broad
      spectrum of pharmacological, therapeutic, cardiovascular and chemopreventive
      properties. The present study was undertaken to determine whether the NM exhibits
      preventive effects on Amio-induced cardiac toxicity. Six-week-old male BALB/c
      mice were divided into four groups (A-D) of six animals per group. Mice in groups
      A and C were fed a regular diet for three weeks, while the diets of the mice in
      groups B and D were supplemented with 1% NM during that period. After three
      weeks, the mice in groups C and D received daily Amio injections of 50 mg/kg body
      weight intraperitoneally for 4 days, whilst those in groups A and B received
      saline alone. At 24 h after the final dose, mice were sacrificed, blood was
      withdrawn and serum was collected for clinical chemistry of the heart enzymes
      creatine phosphokinase (CPK) and aspartate aminotransferase (AST). In addition,
      livers, kidneys, hearts and lungs were excised and weighed. No significant
      differences in weight gain were identified among the groups and liver, kidney,
      heart and lung weights were comparable in all four groups. Administration of Amio
      to group C resulted in a significant increase in serum CPK levels, whereas in NM
      fed group D, the CPK levels were comparable to those in the saline injection
      groups, A and B. Amio administration also resulted in a significant increase in
      serum AST levels in group C, but not in the group D animals which exhibited
      similar levels to those of groups A and B. Therefore, the results indicate that
      NM has the potential to protect against Amio-induced cardiac toxicity.

PMID- 24669264
TI  - Yanshu spraying agent, a traditional Chinese medicine, relieves chronic
      pharyngitis in animals by anti-inflammatory and antibacterial effects.
AB  - Chronic pharyngitis is chronic inflammation that is often caused by repeated
      occurrences of acute pharyngitis or upper respiratory tract infections, including
      Streptococcus and Staphylococcus. The present study aimed to investigate the
      effects of Yanshu spraying agent (Yanshu) in relieving chronic pharyngitis, as
      well as the possible underlying mechanisms. The results revealed that Yanshu
      inhibited chronic inflammation in ammonia-induced chronic pharyngitis in rabbits
      and cotton pellet-induced granuloma tissue formation in rats. Yanshu also
      demonstrated antibacterial effects on Streptococcus and Staphylococcus in vitro.
      Yanshu did not exhibit any effects on the immune system, including the spleen and
      thymus indexes, immunocyte count and monocyte-macrophage function, when compared
      with the effects of dexamethasone. Therefore, the results of the present study
      indicate that Yanshu may relieve chronic pharyngitis via its anti-inflammatory
      and antibacterial activities.

PMID- 24669265
TI  - Clinical characteristics of nonglaucomatous optic disc cupping.
AB  - Pathological optic disc cupping (ODC) is predominantly referred to as glaucoma;
      however, it is not only glaucoma that leads to pathological optic disc
      excavation. A number of other nonglaucomatous diseases also result in optic
      atrophy and excavation of the optic disc. Therefore, in the present study, the
      etiology of nonglaucomatous optic disc cupping (NGODC) was analyzed and
      differentiated from glaucomatous optic disc cupping (GODC). The morphology and
      clinical data of 19 eyes, from 12 patients exhibiting NGODC, were analyzed. Of
      the 12 cases, none were diagnosed with glaucoma, four presented with optic
      neuritis, one with Devic's disease, one with Leber's hereditary optic neuropathy,
      two with pituitary adenoma, one with basal ganglia cerebral hemorrhage, one with
      cilioretinal artery occlusion associated with central retinal vein occlusion, one
      with central retinal artery occlusion and the remaining patient exhibited optic
      nerve injuries. The key features that differentiated NGODC from GODC were the
      color of the optic disc rim and the correlation between visual field defects and
      the disc appearance. The focally notched disc also aided in distinguishing
      between the two disorders. The results of the present study indicated that it is
      critical to acknowledge that nonglaucomatous diseases also lead to ODC and that
      distinguishing between them is necessary.

PMID- 24669266
TI  - Eliminating the effect of pathomorphologically formed sperm on resulting
      gravidity using the intracytoplasmic sperm injection method.
AB  - The aim of the present study was to test whether it is possible to eliminate a
      high percentage of morphologically abnormal sperm in male ejaculate by assisted
      reproduction using the intracytoplasmic sperm injection (ICSI) method. Treatment
      success was evaluated by comparing fertilization, clinical pregnancy and
      reproduction rates between males with heavy teratospermia (<=1% morphologically
      normal spermatozoa) and males with a higher percentage (>1%) of normal sperm. In
      total, 174 patients who had previously undergone 174 ICSI cycles (1 per each
      pair) were evaluated retrospectively. In the group of patients with heavily
      impaired sperm morphology (n=37), the percentage of normal spermatozoa was <=1%.
      In the second group, males with >1% normal spermatozoa (n=137) were considered as
      patients with mildly impaired sperm morphology. The results of partner
      fertilization in these two groups were compared and a lower number of fertilized
      oocytes was identified in the patients with heavily impaired sperm morphology
      (P=0.038). However, neither the gravidity nor the take-home baby rates of the
      partners differed between the patients with mildly and heavily impaired sperm
      morphology. Trends opposite to that for fertilization were observed for gravidity
      and delivery [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.29-1.30; OR,
      0.55; 95% CI, 0.26-1.24, respectively]. This indicates that the lower number of
      fertilized oocytes was not associated with the overall outcome of fertilization
      and that patients with heavily impaired sperm morphology experience the same
      benefit from ICSI as patients with mildly impaired sperm morphology.

PMID- 24669267
TI  - Long-term safety of budesonide/formoterol for the treatment of elderly patients
      with bronchial asthma.
AB  - The long-term safety of budesonide/formoterol (BUD/FM) inhalation has not been
      fully evaluated, particularly in elderly patients with bronchial asthma. To
      evaluate the 12-month safety of BUD/FM inhalation for elderly asthmatic patients,
      the changes in serum potassium levels and pulse rate were examined. A
      retrospective chart review was conducted of consecutive patients who were treated
      with BUD/FM inhalation (two inhalations of 160/4.5 mg, twice daily; Symbicort
      Turbuhaler, AstraZeneca) at a hospital between February 2010 and January 2012. A
      total of 350 patients were treated with BUD/FM inhalation during the study period
      and were followed up over 12 months. The mean age of the patients was 60 years,
      and 19.4% and 21.4% of the patients were aged 65-74 years and >=75 years,
      respectively. One hundred and fourteen (32.6%) of the 350 patients continued the
      inhalation therapy for >12 months. Compared with the pretreatment data,
      reductions in serum potassium levels at 1, 6 and 12 months were not observed,
      even in the patients aged 65-74 and >=75 years. There was also no increase in the
      pulse rate at 1, 6 and 12 months, even in the patients aged 65-74 and >=75 years.
      The usual dosage of BUD/FM showed no adverse effects on the serum potassium
      levels and pulse rate in the adults, including the elderly with persistent
      asthma.

PMID- 24669268
TI  - Inflammatory myofibroblastic tumor of the urinary bladder in a patient with the
      left renal cell carcinoma: A case report.
AB  - This case report describes an inflammatory tumor of the urinary bladder along
      with left renal cell carcinoma which occurred in a 73-year-old male with a
      narrowed orificium urethrae internum and severe hyperplasia of the prostate
      gland. A biopsy was not obtained prior to surgery. An inflammatory
      myofibroblastic tumor (IMT) of the urinary bladder is a rare benign lesion,
      particularly in the elderly. To the best of our knowledge, there are no studies
      concerning IMTs of the urinary bladder in patients with unilateral renal cell
      carcinoma. A bladder lesion due to an IMT may be easily misdiagnosed as
      metastasis from left renal cell carcinoma due to the hypervascularity of the
      tumor. In this case, radical surgery of the cancer of the left kidney was
      performed by laparoscopy. Subsequently, after three weeks and according to the
      examination of the intraoperative frozen-sections, a partial cystectomy was
      performed. Thus, radical resection of the bladder and the associated
      complications were avoided.

PMID- 24669269
TI  - Serum IL-21 levels associated with chronic hepatitis B and hepatitis B-related
      liver failure.
AB  - The aim of the present study was to investigate the role of interleukin (IL)-21
      in chronic hepatitis B virus (HBV) infection. IL-21 stimulates T and B cell
      responses and plays a role in the control of chronic viral infections. Serum IL
      21 levels were measured by enzyme immunoassay in 109 patients with chronic HBV
      infection at various clinical stages, as well as in 19 healthy controls (HCs).
      The proportion of T cells producing IL-21 in the peripheral blood was assessed by
      intracellular cytokine staining and flow cytometry. Mean serum IL-21 levels in
      patients with chronic hepatitis B (CHB) and the HCs were 303.54+/-152.77 pg/ml
      and 68.24+/-9.06 pg/ml, respectively (P=0.003). In addition, the mean serum IL-21
      level in patients with hepatitis B-related acute-on-chronic liver failure (HB
      ACLF) was 455.38+/-412.38 pg/ml, which exhibited a statistically significant
      difference when compared with the HCs (P=0.000). Serum IL-21 levels were highest
      in the patients with HB-ACLF (455.38+/-412.38 pg/ml) and exhibited a significant
      difference when compared with the CHB patients (P=0.04). The mean serum IL-21
      levels in patients with cirrhosis also increased, but there was no statistically
      significant difference when compared with the HCs (P=0.82). The frequency of IL
      21+CD4+ cells also increased compared with the HCs and correlated with the number
      and percentage of lymphocytes in the peripheral blood. Serum IL-21 levels
      increased in CHB and HB-ACLF patients. Relatively low serum IL-21 levels in CHB
      may have a causal role in the persistence of HBV infection. Higher serum levels
      in HB-ACLF may activate T and B cells to eliminate the virus or injure the liver
      via the release of inflammatory cytokines.

PMID- 24669270
TI  - Laryngeal schwannoma excised under a microlaryngoscope without tracheotomy: A
      case report.
AB  - Schwannomas are benign encapsulated tumors arising from Schwann cells in the
      peripheral nervous system. Between 25 and 45% of schwannomas occur in the head
      and neck region. Schwannomas of the larynx are extremely rare with an incidence
      of 0.1-1.5% in all benign laryngeal tumors. Laryngeal schwannomas usually occur
      in females aged between their 4th and 5th decades. The most successful curative
      method is surgical resection. When selecting the surgical method, the size and
      location of the tumor, as well as the requests of the patient, should be
      considered. The present case report describes a 29-year-old female patient with
      symptoms of hoarseness and dyspnea on exertion. Through endoscopic biopsy,
      histopathology revealed a schwannoma. Considering the symptoms, age and
      preferences of the patient, the method of trans-oral microlaryngoscopic excision
      without tracheotomy was used to excise the tumor located in the aryepiglottic
      fold. Results from a short-term follow-up showed the postoperative result to be
      satisfactory.

PMID- 24669271
TI  - Analysis of the association between adiponectin, adiponectin receptor 1 and
      diabetic cardiomyopathy.
AB  - The aim of this study was to explore the association between adiponectin (APN),
      APN receptors and insulin resistance (IR) using rats with type 2 diabetes
      mellitus (T2DM) as a model of diabetic cardiomyopathy (DC). Serum and cardiac APN
      levels were assessed using a double-antibody sandwich ELISA. In addition, the
      mRNA and protein expression of the myocardial APN receptor 1 (AdipoR1) was
      determined using the reverse transcription polymerase chain reaction and
      immunohistochemical staining. The results showed that the heart weight/body
      weight ratio, fasting plasma glucose (FPG) and lipid levels, and the homeostasis
      model assessment-estimated IR (HOMA-IR) index were elevated in the T2DM group
      compared with the control group. Cardiac function was significantly lower in the
      T2DM group compared with the control group (P<0.05). Furthermore, serum and
      cardiac APN levels were significantly reduced in the T2DM group compared with the
      control group, and mRNA and protein expression of AdipoR1 was lower in the T2DM
      group compared with the control group (P<0.05). Changes in the morphology of
      myocardial cells were observed under the light microscope using hematoxylin and
      eosin staining. Myocardial cell hypertrophy, a disordered cell arrangement and
      irregular nuclear size were observed in the T2DM group. By contrast, myocardial
      cells in the control group were arranged in neat rows with uniform cytoplasmic
      and nuclear staining. According to the correlation analyses, serum APN levels in
      the T2DM group were negatively correlated with FPG, triglyceride, total
      cholesterol and fasting insulin (FINS) levels, as well as with the HOMA-IR index.
      Myocardial AdipoR1 protein expression was positively correlated with myocardial
      APN levels, and negatively correlated with FINS and HOMA-IR. It may be concluded
      that myocardial and serum levels of APN are reduced in rats with DC. Metabolic
      disorders of blood glucose and lipid levels, as well as IR, are associated with
      low APN levels. Furthermore, low levels of myocardial Adipo1R mRNA and protein
      expression correlate with reduced insulin sensitivity.

PMID- 24669272
TI  - Diagnostic feature of tuberculous peritonitis in patients with cirrhosis: A
      matched case-control study.
AB  - The aim of the present study was to compare the clinical characteristics of
      tuberculous peritonitis (TBP) and spontaneous bacterial peritonitis (SBP) in
      patients with cirrhosis. A retrospective, matched case-control study was
      conducted consisting of 12 patients with cirrhosis diagnosed with TBP between
      2008 and 2011. Control subjects were patients with SBP. Clinical features and
      laboratory data were analyzed. Compared with SBP, TBP in patients with cirrhosis
      was frequently associated with extraperitoneal tuberculosis (25 vs. 0%), a more
      insidious onset (39.67+/-30.00 vs. 21.60+/-21.50 days; P<0.05), Child-Pugh
      classification B at onset (67 vs. 32%; P<0.05) and lymphopenia (0.67+/-0.22 vs.
      1.19+/-0.41*109/l; P<0.01). Patients with TBP tended to have lymphocytic
      predominance in the peritoneal fluid (92%), while patients with SBP tended to
      have neutrophil predominance (68%). Compared with the SBP group, the TBP group
      had significantly higher ascitic protein, adenosine deaminase (ADA) and lactate
      dehydrogenase (LDH) levels. Ascitic protein levels were >25 g/l in 9 patients
      (75%) in the TBP group and in 2 patients (8%) in the SBP group; ascitic ADA
      activity levels were >27 U/l in 8 patients (67%) in the TBP group, but were not
      >27 U/l in any of the patients in the SBP group; ascitic LDH levels were >90 U/l
      in 10 patients (83%) in the TBP group and 5 patients (20%) in the SBP group.
      Therefore, the results of the present study indicate that TBP should be
      considered in cirrhotic patients with relevant clinical manifestations and
      characteristics of laboratory observations.

PMID- 24669273
TI  - Chinese medicinal formula Guanxin Shutong capsule protects the heart against
      oxidative stress and apoptosis induced by ischemic myocardial injury in rats.
AB  - Guanxin Shutong capsule (GXSTC) is a Chinese medicinal formula that has been used
      clinically for the treatment of chest pain, depression, palpitation and
      cardiovascular diseases in China for almost 10 years. The aim of the present
      study was to investigate the protective mechanisms against oxidative stress and
      apoptosis that GXSTC exhibits in the hearts of rats with myocardial ischemia
      (MI). Infarct size and the levels of marker enzymes, including serum creatine
      kinase-isoenzyme (CK-MB), lactate dehydrogenase (LDH) and glutamate oxaloacetic
      transaminase (GOT), as well as the levels of nitric oxide (NO) and NO synthase
      (NOS) in the heart were measured by biochemical analysis assays. Levels of the
      antioxidants superoxide dismutase (SOD), catalase (CATA), and glutathione (GSH),
      and the oxidative stress marker malondialdehyde (MDA), were also determined.
      Following a 6-week period of ischemia, myocardial apoptosis, as well as the
      protein and mRNA expression of NADPH oxidase, was evaluated. Myocardial NADPH
      oxidase activity was measured by protein expression of p47phox and gp91phox using
      western blot analysis and mRNA expression of p22phox, p47phox, p67phox and
      gp91phox using reverse transcription polymerase chain reaction. The results
      showed that daily oral treatment of the rats with GXSTC reduced infarct size,
      myocardial apoptosis, the levels of serum MDA, LDH, CK-MB and GOT and heart GOT,
      and increased the activities of total SOD, CATA, NOS and the levels of NO and GSH
      compared with those in vehicle-treated MI model rats. Administration of GXSTC for
      6 weeks also reduced the mRNA expression of the NADPH oxidase subunits p47phox
      and gp91phox protein, as well as the expression of Bax and caspase-3 proteins. By
      contrast, Bcl-2 protein expression increased. In conclusion, the results
      demonstrate that GXSTC attenuates myocardial injury via antioxidative and
      antiapoptotic effects.

PMID- 24669274
TI  - Prevention of Adriamycin-induced hepatic and renal toxicity in male BALB/c mice
      by a nutrient mixture.
AB  - Adriamycin (ADR), an antineoplastic antibiotic used in cancer therapy, is
      associated with toxicity to vital organs with long-term use. A nutrient mixture
      (NM) has previously been shown to exhibit a broad spectrum of therapeutic
      properties. The aim of the present study was to determine whether the NM is
      useful for preventing ADR-induced hepatic and nephric toxicity. Six-week-old male
      BALB/c mice were divided into four groups of six animals each. Groups A and C
      were fed a regular diet for three weeks and groups B and D were fed a diet
      supplemented with 1% NM. After three weeks, the mice in groups C and D received
      20 mg/kg body weight ADR intraperitoneally, while those in groups A and B
      received saline alone. Animals were sacrificed after 24 h, blood samples were
      collected and serum was obtained for clinical chemistry. Organs were also excised
      and weighed. Administration of ADR to group C (control diet) resulted in a marked
      increase in hepatic alanine aminotransferase, aspartate aminotransferase and
      gamma-glutamyl transferase levels and renal blood urea nitrogen, creatinine and
      uric acid serum markers. However, in group D (NM 1% diet), the serum markers were
      comparable with the levels of group A and B. Therefore, the results indicate that
      NM has the potential to protect against ADR-induced hepatic and nephric damage.

PMID- 24669275
TI  - Decreased expression of neuronal Per-Arnt-Sim domain protein 4 gene in the
      hippocampus of a post-stroke depression rat model.
AB  - Neuronal Per-Arnt-Sim domain protein 4 (NPAS4) is important in regulating
      transcription and function in the limbic system and in brain development. Post
      stroke depression (PSD) is a common complication following a stroke. Furthermore,
      organic damage as a result of a stroke affects the restoration of nerve function
      and indicates that hippocampal neural activity may be associated with PSD. A PSD
      rat model was established via a middle cerebral artery occlusion procedure, which
      was combined with isolation and chronic unexpected mild stress, and was used to
      investigate the expression of the NPAS4 gene in the hippocampus. The neurological
      deficit and behavior were evaluated and NPAS4 mRNA expression was measured by
      semi-quantitative reverse transcription-polymerase chain reaction; furthermore,
      the association with cognitive impairment was analyzed. The PSD rats displayed
      neuropsychopathic disorders and the NPAS4 mRNA expression levels in the
      hippocampus were significantly lower in the depression and PSD groups compared
      with the control group. Therefore, the present study identified that NPAS4
      expression was decreased in the hippocampus of PSD rats.

PMID- 24669276
TI  - Noninvasive theranostic imaging of HSV1-sr39TK-NTR/GCV-CB1954 dual-prodrug
      therapy in metastatic lung lesions of MDA-MB-231 triple negative breast cancer in
      mice.
AB  - Metastatic breast cancer is an obdurate cancer type that is not amenable to
      chemotherapy regimens currently used in clinic. There is a desperate need for
      alternative therapies to treat this resistant cancer type. Gene-Directed Enzyme
      Prodrug Therapy (GDEPT) is a superior gene therapy method when compared to
      chemotherapy and radiotherapy procedures, proven to be effective against many
      types of cancer in pre-clinical evaluations and clinical trials. Gene therapy
      that utilizes a single enzyme/prodrug combination targeting a single cellular
      mechanism needs significant overexpression of delivered therapeutic gene in order
      to achieve therapy response. Hence, to overcome this obstacle we recently
      developed a dual therapeutic reporter gene fusion that uses two different
      prodrugs, targeting two distinct cellular mechanisms in order to achieve
      effective therapy with a limited expression of delivered transgenes. In addition,
      imaging therapeutic reporter genes offers additional information that indirectly
      correlates gene delivery, expression, and functional effectiveness as a
      theranostic approach. In the present study, we evaluate the therapeutic potential
      of HSV1-sr39TK-NTR fusion dual suicide gene therapy system that we recently
      developed, in MDA-MB-231 triple negative breast cancer lung-metastatic lesions in
      a mouse model. We compared the therapeutic potential of HSV1-sr39TK-NTR fusion
      with respective dual prodrugs GCV-CB1954 with HSV1-sr39TK/GCV and NTR/CB1954
      single enzyme prodrug system in this highly resistant metastatic lesion of the
      lungs. In vitro optimization of dose and duration of exposure to GCV and CB1954
      was performed in MDA-MB-231 cells. Drug combinations of 1 MUg/ml GCV and 10 MUM
      CB1954 for 3 days was found to be optimal regimen for induction of significant
      cell death, as assessed by FACS analysis. In vivo therapeutic evaluation in
      animal models showed a complete ablation of lung metastatic nodules of MDA-MB-231
      triple negative breast cancer cells following two consecutive doses of a
      combination of GCV (40 mg/kg) and CB1954 (40 mg/kg) administered at 5 day
      intervals. In contrast, the respective treatment condition in animals expressing
      HSV1-sr39TK or NTR separately, showed minimal or no effect on tumor reduction as
      measured by bioluminescence (tumor mass) and [(18)F]-FHBG microPET (TK
      expression) imaging. These highlight the strong therapeutic effect of the dual
      fusion prodrug therapy and its use in theranostic imaging of tumor monitoring in
      living animals by multimodality molecular imaging. 

PMID- 24669277
TI  - Myocardial protective effect of extracellular superoxide dismutase gene modified
      bone marrow mesenchymal stromal cells on infarcted mice hearts.
AB  - AIM: Extracellular superoxide dismutase (ecSOD) is a unique scavenger of
      superoxide anions and a promising target of gene therapy for ischemia/reperfusion
      injury (I/R). However, conventional gene therapies have limitation in
      effectiveness and efficiency. This study aimed to investigate the protective
      effects of ecSOD gene modified bone marrow mesenchymal stromal cells (BMSCs) on
      cardiac function improvement in mice infarcted heart. METHODS & RESULTS: BMSCs
      were isolated from Fluc(+) transgenic mice (Tg FVB[Fluc(+)]) and transfected by
      adenovirus combined with human ecSOD gene. ELISA was performed to determine ecSOD
      protein level. Female syngeneic FVB mice were randomized into 5 groups: (1) Sham
      group (sham); (2) MI group (MI); (3) MI+BMSCs group (BMSC); (4) MI+BMSCs-vector
      group (BMSC-vector); (5) MI+ BMSCs-ecSOD group (BMSC-ecSOD). MI was accomplished
      by ligation of the left anterior descending artery. BMSCs (2 x 10(6)) were
      injected into the border zone of infarction. In vivo bioluminescence imaging
      (BLI) was performed to monitor transplanted BMSCs viability. Echocardiography and
      histological staining revealed that BMSCs-ecSOD significantly reduced myocardial
      infarction size and improved cardiac function. Lucigenin chemiluminescence, DHE
      and TUNEL staining demonstrated that BMSCs-ecSOD delivery reduced ROS level and
      cell apoptosis both in vivo and in vitro. Western blot assay revealed that ecSOD
      supplementation increased FoxO3a phosphorylation in cardiomyocytes. Moreover,
      quantitative real-time PCR showed that pro-apoptotic factors (bim and bax) were
      decreased while the anti-apoptotic factor mir-21 expression was increased after
      ecSOD intervention. CONCLUSION: Intra-myocardial transplantation of adenovirus
      ecSOD transfected BMSCs could exert potential cardiac protection against MI,
      which may be partly through reduction of oxidative stress and improvement of
      BMSCs survival.

PMID- 24669278
TI  - Protection against lethal enterovirus 71 challenge in mice by a recombinant
      vaccine candidate containing a broadly cross-neutralizing epitope within the VP2
      EF loop.
AB  - Human enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth
      disease (HFMD) and is associated with several severe neurological complications
      in the Asia-Pacific region. Here, we evaluated that while passive transfer of
      neutralizing monoclonal antibody (nMAb) against the VP2 protein protect against
      lethal EV71 infection in BALB/c mice. Protective nMAb were mapped to residues 141
      155 of VP2 by peptide ELISA. High-resolution structural analysis showed that the
      epitope is part of the VP2 EF loop, which is the "puff" region that forms the
      "southern rim" of the canyon. Moreover, a three-dimensional structural
      characterization for the puff region with prior neutralizing epitopes and
      receptor-binding sites that can serve to inform vaccine strategies.
      Interestingly, using hepatitis B virus core protein (HBc) as a carrier, we
      demonstrated that the cross-neutralizing EV71 antibodies were induced, and the
      VP2 epitope immunized mice serum also conferred 100% in vivo passive protection.
      The mechanism of in vivo protection conferred by VP2 nMAb is in part attributed
      to the in vitro neutralizing titer and ability to bind authentic viral particles.
      Importantly, the anti-VP2(aa141-155) antibodies could inhibit the binding of
      human serum to EV71 virions showed that the VP2 epitope is immunodominant.
      Collectively, our results suggest that a broad-spectrum vaccine strategy
      targeting the high-affinity epitope of VP2 EF loop may elicits effective immune
      responses against EV71 infection. 

PMID- 24669279
TI  - A synergistic therapeutic scheme for hyperglycemia and nephrotic disorders in
      diabetes.
AB  - We previously demonstrated that the utilization of an electrospun scaffold could
      boost functional outputs of transplanted islets. In this study, we aim to develop
      a drug-eluting scaffold with a payload of pioglitazone to simultaneously rein in
      hyperglycemia and recoup lost renal functions in diabetic mice that underwent
      islet transplantation. The in vivo proliferation of islets was measured by a non
      invasive bio-imaging technology whereas the blood insulin, blood glucose and
      renal proteins were assayed. The local stimulation of transplanted islets by
      pioglitazone saw an accelerated in vivo proliferation without apoptosis caused by
      the drug-eluting scaffold. In addition, pioglitazone contributed to an increased
      secretion of insulin and C-peptide 2, giving rise to an accelerated rein-in of
      hyperglycemia and enhanced tolerance of sudden oral glucose challenge. Moreover,
      the accelerated decrease of blood creatinine, urine creatinine and blood urea
      nitrogen suggested that pioglitazone contributed to the recovery of renal
      functions compromised by diabetes. Our bioengineering strategy effectively
      ameliorated hyperglycemia and associated nephrotic disorders, and shed a new
      light on an engineering approach to combat diabetes. 

PMID- 24669280
TI  - Radiological imaging in pediatric rheumatic diseases.
AB  - Radiological imaging plays a fundamental role in the diagnosis and monitoring of
      rheumatic diseases. The basic method of imaging is a classic X-ray picture, which
      for many years has been used as a single method for the recognition and
      evaluation of the effects of disease management. In today's modern day treatment
      of rheumatic diseases, ultrasonography and magnetic resonance are more commonly
      performed for early detection of inflammatory changes in the region of soft
      tissue, subchondral bone and bone marrow. In spite of their usefulness and
      fundamental role in the diagnosis, X-ray still remains an essential tool in the
      diagnosis of rheumatoid arthritis in children and is complementary to today's
      methods of imaging diagnostics. In clinical practice, X-ray imaging is still an
      important examination performed not only to recognize the disorders, but also to
      provide a differential diagnosis. It helps estimate disease progression and is
      used to monitor the effects of treatment and the development of possible
      complications. Differential diagnosis of rheumatic diseases is performed on the
      basis of localization and type of radiographic changes. The surrounding
      periarticular soft tissues, bone structures, joint space, with special attention
      to articular bone surfaces and epiphyses, are analyzed. The aim of this work is
      to describe characteristic inflammatory changes present on X-ray imaging typical
      for the most commonly diagnosed rheumatic diseases in children, such as juvenile
      idiopathic arthritis, systemic lupus erythematosus, systemic scleroderma, mixed
      connective tissue disease, juvenile dermatomyositis, juvenile spondyloarthropathy
      and systemic vascular disease. 

PMID- 24669281
TI  - Catalase influence in the regulation of coronary resistance by estrogen: joint
      action of nitric oxide and hydrogen peroxide.
AB  - We tested the influence of estrogen on coronary resistance regulation by
      modulating nitric oxide (NO) and hydrogen peroxide (H2O2) levels in female rats.
      For this, estrogen levels were manipulated and the hearts were immediately
      excised and perfused at a constant flow using a Langendorff's apparatus. Higher
      estrogen levels were associated with a lower coronary resistance, increased
      nitric oxide bioavailability, and higher levels of H2O2. When oxide nitric
      synthase blockade by L-NAME was performed, no significant changes were found in
      coronary resistance of ovariectomized rats. Additionally, we found an inverse
      association between NO levels and catalase activity. Taken together, our data
      suggest that, in the absence of estrogen influence and, therefore, reduced NO
      bioavailability, coronary resistance regulation seems to be more dependent on the
      H2O2 that is maintained at low levels by increased catalase activity. 

PMID- 24669282
TI  - Propofol activation of the Nrf2 pathway is associated with amelioration of acute
      lung injury in a rat liver transplantation model.
AB  - OBJECTIVE: This study aimed to investigate whether propofol pretreatment can
      protect against liver transplantation-induced acute lung injury (ALI) and to
      explore whether Nrf2 pathway is involved in the protections provided by propofol
      pretreatment. METHOD: Adult male Sprague-Dawley rats were divided into five
      groups based on the random number table. Lung pathology was observed by optical
      microscopy. Lung water content was assessed by wet/dry ratio, and PaO2 was
      detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were
      determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear
      Nrf2 was assayed by western blotting. RESULTS: Compared with saline-treated model
      group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung
      injury caused by orthotopic autologous liver transplantation (OALT), decrease the
      lung injury scores, lung water content, and H2O2 and MDA levels, and improve the
      arterial PaO2 and SOD activity. Furthermore, propofol (but not N-acetylcysteine)
      pretreatment especially in high dose inhibited the expression of Keap1 and
      induced translocation of Nrf2 into the nucleus to further upregulate the
      expression of HO-1 and NQO1 downstream. CONCLUSION: Pretreatment with propofol is
      associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved
      in the antioxidative processes.

PMID- 24669283
TI  - NADPH oxidase 1 and its derived reactive oxygen species mediated tissue injury
      and repair.
AB  - Reactive oxygen species are mostly viewed to cause oxidative damage to various
      cells and induce organ dysfunction after ischemia-reperfusion injury. However,
      they are also considered as crucial molecules for cellular signal transduction in
      biology. NADPH oxidase, whose only function is reactive oxygen species
      production, has been extensively investigated in many cell types especially
      phagocytes. The deficiency of NADPH oxidase extends the process of inflammation
      and delays tissue repair, which causes chronic granulomatous disease in patients.
      NADPH oxidase 1, one member of the NADPH oxidase family, is not only
      constitutively expressed in a variety of tissues, but also induced to increase
      expression in both mRNA and protein levels under many circumstances. NADPH
      oxidase 1 and its derived reactive oxygen species are suggested to be able to
      regulate inflammation reaction, cell proliferation and migration, and
      extracellular matrix synthesis, which contribute to the processes of tissue
      injury and repair. 

PMID- 24669284
TI  - Saponins from Aralia taibaiensis attenuate D-galactose-induced aging in rats by
      activating FOXO3a and Nrf2 pathways.
AB  - Reactive oxygen species (ROS) are closely related to the aging process. In our
      previous studies, we found that the saponins from Aralia taibaiensis have potent
      antioxidant activity, suggesting the potential protective activity on the aging.
      However, the protective effect of the saponins and the possible underlying
      molecular mechanism remain unknown. In the present study, we employed a D
      galactose-induced aging rat model to investigate the protective effect of the
      saponins. We found that D-galactose treatment induced obvious aging-related
      changes such as the decreased thymus and spleen coefficients, the increased
      advanced glycation end products (AGEs) level, senescence-associated beta
      galactosidase (SAbeta-gal) activity, and malondialdehyde (MDA) level. Further
      results showed that Forkhead box O3a (FOXO3a), nuclear factor-erythroid 2-related
      factor 2 (Nrf2), and their targeted antioxidants such as superoxide dismutase 2
      (SOD2), catalase (CAT), glutathione reductase (GR), glutathione (GSH), glutamate
      cysteine ligase (GCL), and heme oxygenase 1 (HO-1) were all inhibited in the
      aging rats induced by D-galactose treatment. Saponins supplementation showed
      effective protection on these changes. These results demonstrate that saponins
      from Aralia taibaiensis attenuate the D-galactose-induced rat aging. By
      activating FOXO3a and Nrf2 pathways, saponins increase their downstream multiple
      antioxidants expression and function, at least in part contributing to the
      protection on the D-galactose-induced aging in rats.

PMID- 24669285
TI  - Antiaging properties of a grape-derived antioxidant are regulated by
      mitochondrial balance of fusion and fission leading to mitophagy triggered by a
      signaling network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN.
AB  - It was proposed that resveratrol, a polyphenolic antioxidant and a calorie
      restriction mimetic could promote longevity but subsequent studies could not
      prove this. The original proposal was based on the fact that a grape-derived
      antioxidant could activate the antiaging gene Sirt1. Most studies agree that
      indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause
      or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was
      found to be activated. The present study on ischemic reperfusion (I/R) in rat
      hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation,
      which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the
      activation of mitochondrial fission and mitophagy. Confocal microscopy
      conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and
      PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission
      electron microscopy. Western blot analyses data are consistent with the results
      of confocal microscopy. It appears that the grape-derived antioxidant modifies
      the intracellular environment by changing the oxidizing milieu into a reducing
      milieu and upregulating intracellular glutathione, potentiates a signal
      transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial
      fusion fission-mitophagy that leads to cardioprotection, and paves the way to an
      anti-aging environment. 

PMID- 24669286
TI  - Early onset Alzheimer's disease and oxidative stress.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in elderly adults.
      It is estimated that 10% of the world's population aged more than 60-65 years
      could currently be affected by AD, and that in the next 20 years, there could be
      more than 30 million people affected by this pathology. One of the great
      challenges in this regard is that AD is not just a scientific problem; it is
      associated with major psychosocial and ethical dilemmas and has a negative impact
      on national economies. The neurodegenerative process that occurs in AD involves a
      specific nervous cell dysfunction, which leads to neuronal death. Mutations in
      APP, PS1, and PS2 genes are causes for early onset AD. Several animal models have
      demonstrated that alterations in these proteins are able to induce oxidative
      damage, which in turn favors the development of AD. This paper provides a review
      of many, although not all, of the mutations present in patients with familial
      Alzheimer's disease and the association between some of these mutations with both
      oxidative damage and the development of the pathology. 

PMID- 24669289
TI  - Brugada phenocopy: A new electrocardiogram phenomenon.
AB  - Brugada phenocopies (BrP) are clinical entities that are etiologically distinct
      from true congenital Brugada syndrome. BrP are characterized by type 1 or type 2
      Brugada electrocardiogram (ECG) patterns in precordial leads V1-V3. However, BrP
      are elicited by various underlying clinical conditions such as myocardial
      ischemia, pulmonary embolism, electrolyte abnormalities, or poor ECG filters.
      Upon resolution of the inciting underlying pathological condition, the BrP ECG
      subsequently normalizes. To date, reports have documented BrP in the context of
      singular clinical events. More recently, recurrent BrP has been demonstrated in
      the context of recurrent hypokalemia. This demonstrates clinical reproducibility,
      thereby advancing the concept of this new ECG phenomenon. The key to further
      understanding the pathophysiological mechanisms behind BrP requires experimental
      model validation in which these phenomena are reproduced under strictly
      controlled environmental conditions. The development of these validation models
      will help us determine whether BrP are transient alterations of sodium channels
      that are not reproducible with a sodium channel provocative test or
      alternatively, a malfunction of other ion channels. In this editorial, we discuss
      the conceptual emergence of BrP as a new ECG phenomenon, review the progress made
      to date and identify opportunities for further investigation. In addition, we
      also encourage investigators that are currently reporting on these cases to use
      the term BrP in order to facilitate literature searches and to help establish
      this emerging concept. 

PMID- 24669287
TI  - Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in
      myelodysplastic syndromes in the context of clinical outcomes and as a
      consequence of iron overload.
AB  - The role of oxidative stress in the initiation and progression of myelodysplastic
      syndromes (MDS) as a consequence of iron overload remains unclear. In this study
      we have simultaneously quantified plasma low-molecular-weight aminothiols,
      malondialdehyde, nitrite, and nitrate and have studied their correlation with
      serum iron/ferritin levels, patient treatment (chelation therapy), and clinical
      outcomes. We found significantly elevated plasma levels of total, oxidized, and
      reduced forms of cysteine (P < 0.001), homocysteine (P < 0.001), and
      cysteinylglycine (P < 0.006) and significantly depressed levels of total and
      oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients
      compared to healthy donors. Moreover, total (P < 0.032) and oxidized
      cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly
      between the analyzed MDS subgroups with different clinical classifications.
      Malondialdehyde levels in plasma correlated moderately with both serum ferritin
      levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and
      were significantly higher in patients with iron overload. The other analyzed
      compounds lacked correlation with iron overload (represented by serum
      iron/ferritin levels). For the first time our results have revealed significant
      differences in the concentrations of plasma aminothiols in MDS patients, when
      compared to healthy donors. We found no correlation of these parameters with iron
      overload and suggest the role of oxidative stress in the development of MDS
      disease.

PMID- 24669288
TI  - Oxidative stress in Alzheimer's disease: why did antioxidant therapy fail?
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly, with
      increasing prevalence and no disease-modifying treatment available yet. A
      remarkable amount of data supports the hypothesis that oxidative stress is an
      early and important pathogenic operator in AD. However, all clinical studies
      conducted to date did not prove a clear beneficial effect of antioxidant
      treatment in AD patients. In the current work, we review the current knowledge
      about oxidative stress in AD pathogeny and we suggest future paths that are worth
      to be explored in animal models and clinical studies, in order to get a better
      approach of oxidative imbalance in this inexorable neurodegenerative disease. 

PMID- 24669290
TI  - Peripartum cardiomyopathy: A puzzle closer to solution.
AB  - Peripartum cardiomyopathy (PPCM) represents new heart failure in a previously
      heart-healthy peripartum patient. It is necessary to rule out all other known
      causes of heart failure before accepting a diagnosis of PPCM. The modern era for
      PPCM in the United States and beyond began with the report of the National
      Institutes of Health PPCM Workshop in 2000, clarifying all then-currently known
      aspects of the disease. Since then, hundreds of publications have appeared, an
      indication of how devastating this disease can be to young mothers and their
      families and the urgent desire to find solutions for its cause and better
      treatment. The purpose of this review is to highlight the important advances that
      have brought us nearer to the solution of this puzzle, focusing on what we have
      learned about PPCM since 2000; and what still remains unanswered. Despite many
      improvements in outcome, we still do not know the actual triggers that initiate
      the pathological process; but realize that cardiac angiogenic imbalances
      resulting from complex pregnancy-related immune system and hormonal changes play
      a key role. 

PMID- 24669291
TI  - Cardioprotection and pharmacological therapies in acute myocardial infarction:
      Challenges in the current era.
AB  - In patients with an acute ST-segment elevation myocardial infarction, timely
      myocardial reperfusion using primary percutaneous coronary intervention is the
      most effective therapy for limiting myocardial infarct size, preserving left
      ventricular systolic function and reducing the onset of heart failure. Within
      minutes after the restoration of blood flow, however, reperfusion itself results
      in additional damage, also known as myocardial ischemia-reperfusion injury. An
      improved understanding of the pathophysiological mechanisms underlying
      reperfusion injury has resulted in the identification of several promising
      pharmacological (cyclosporin-A, exenatide, glucose-insulin-potassium, atrial
      natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and
      melatonin) therapeutic strategies for reducing the severity of myocardial
      reperfusion injury. Many of these agents have shown promise in initial proof-of
      principle clinical studies. In this article, we review the pathophysiology
      underlying myocardial reperfusion injury and highlight the potential
      pharmacological interventions which could be used in the future to prevent
      reperfusion injury and improve clinical outcomes in patients with coronary heart
      disease. 

PMID- 24669292
TI  - Shellfish allergy and relation to iodinated contrast media: United Kingdom
      survey.
AB  - AIM: To assess current practice of United Kingdom cardiologists with respect to
      patients with reported shellfish/iodine allergy, and in particular the use of
      iodinated contrast for elective coronary angiography. Moreover we have reviewed
      the current evidence-base and guidelines available in this area. METHODS: A
      questionnaire survey was send to 500 senior United Kingdom cardiologists (almost
      50% cardiologists registered with British Cardiovascular Society) using email and
      first 100 responses used to analyze practise. We involved cardiologists
      performing coronary angiograms routinely both at secondary and tertiary centres.
      Three specific questions relating to allergy were asked: (1) History of
      shellfish/iodine allergy in pre-angiography assessment; (2) Treatments offered
      for shellfish/iodine allergy individuals; and (3) Any specific treatment protocol
      for shellfish/iodine allergy cases. We aimed to establish routine practice in
      United Kingdom for patients undergoing elective coronary angiography. We also
      performed comprehensive PubMed search for the available evidence of relationship
      between shellfish/iodine allergy and contrast media. RESULTS: A total of 100
      responses were received, representing 20% of all United Kingdom cardiologists.
      Ninety-three replies were received from consultant cardiologists, 4 from non
      consultant grades and 3 from cardiology specialist nurses. Amongst the
      respondents, 66% routinely asked about a previous history of shellfish/iodine
      allergy. Fifty-six percent would pre-treat these patients with steroids and anti
      histamines. The other 44% do nothing, or do nonspecific testing based on their
      personal experience as following: (1) Skin test with 1 mL of subcutaneous
      contrast before intravenous contrast; (2) Test dose 2 mL contrast before coronary
      injection; (3) Close observation for shellfish allergy patients; and (4) Minimal
      evidence that the steroid and anti-histamine regime is effective but it makes us
      feel better. CONCLUSION: There is no evidence that allergy to shellfish alters
      the risk of reaction to intravenous contrast more than any other allergy and
      asking about such allergies in pre-angiogram assessment will not provide any
      additional information except propagating the myth.

PMID- 24669293
TI  - Steal syndrome secondary to coronary artery fistulae associated with giant
      aneurysm.
AB  - Giant coronary artery aneurysms and coronary artery fistulae are uncommon
      pathologies. We present the case of an elderly woman who was referred to
      cardiology for investigation of possible ischaemic heart disease prior to
      orthopaedic surgery. The patient had developed chest pain in the setting of a
      septic total knee replacement associated with changes on electrocardiography.
      Coronary angiography revealed multiple coronary arteriovenous fistulae associated
      with giant coronary artery aneurysm causing steal syndrome in the setting of
      haemodynamic stress. 

PMID- 24669294
TI  - The M1 and M2 paradigm of macrophage activation: time for reassessment.
AB  - Macrophages are endowed with a variety of receptors for lineage-determining
      growth factors, T helper (Th) cell cytokines, and B cell, host, and microbial
      products. In tissues, macrophages mature and are activated in a dynamic response
      to combinations of these stimuli to acquire specialized functional phenotypes. As
      for the lymphocyte system, a dichotomy has been proposed for macrophage
      activation: classic vs. alternative, also M1 and M2, respectively. In view of
      recent research about macrophage functions and the increasing number of immune
      relevant ligands, a revision of the model is needed. Here, we assess how
      cytokines and pathogen signals influence their functional phenotypes and the
      evidence for M1 and M2 functions and revisit a paradigm initially based on the
      role of a restricted set of selected ligands in the immune response. 

PMID- 24669295
TI  - Why is the neural control of cerebral autoregulation so controversial?
AB  - Cerebral autoregulation refers to the mechanisms that act to keep cerebral blood
      flow (CBF) constant during changes in blood pressure. The mechanisms of cerebral
      autoregulation, especially in humans, are poorly understood but are undoubtedly
      multifactorial and likely reflect many redundant pathways that potentially differ
      between species. Whether sympathetic nervous activity influences CBF and/or
      cerebral autoregulation in humans remains controversial. Following a brief
      introduction to cerebral autoregulation, this review highlights the likely
      reasons behind the controversy of the neural control of cerebral autoregulation.
      Finally, suggestions are provided for further studies to improve the
      understanding of the neural control of CBF regulation. 

PMID- 24669296
TI  - Quality control in mitochondria: use it, break it, fix it, trash it.
AB  - Repairing or disposing of a malfunctioning object is an everyday dilemma.
      Replacing an item may be quicker than repairing it, but may also be more costly.
      Cells are faced with the same options when their organelles are challenged.
      Ensuring the health of the mitochondrial network is of utmost importance for
      cellular health and, not surprisingly, mitochondrial quality control can take
      both the repair and disposal routes. Spectacular advances have been made in
      recent years and a picture is starting to emerge of what drives a cell to take
      one or the other path. Interestingly, mitochondrial quality control seems to be
      deficient in various medically relevant conditions, such as neurodegeneration and
      aging. 

PMID- 24669297
TI  - The treatment of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and invariably fatal disease
      with a median survival of less than three years from diagnosis. The last decade
      has seen an exponential increase in clinical trial activity in IPF and this in
      turn has led to important developments in the treatment of this terrible disease.
      Previous therapeutic approaches based around regimens including corticosteroids
      and azathioprine have, when tested in randomized clinical trials, been shown to
      be harmful in IPF. By contrast, compounds with anti-fibrotic actions have been
      shown to be beneficial. Subsequently, the novel anti-fibrotic agent pirfenidone
      has, in many parts of the world, become the first treatment ever to be licensed
      for use in IPF. This exciting development, coupled with ongoing clinical trials
      of a range of other novel compounds, is bringing hope to patients and their
      clinicians and raises the prospect that, in the future, it may become possible to
      successfully arrest the development of progressive scarring in IPF. 

PMID- 24669298
TI  - Treatment of dyslipidemia.
AB  - Atherosclerotic cardiovascular disease (including coronary heart disease, stroke
      and peripheral arterial disease) is the leading cause of death globally. Abnormal
      blood lipids (dyslipidemia), smoking, and high blood pressure are responsible for
      more than 75% of cases. Aggressive low-density lipoprotein (LDL)-cholesterol
      lowering therapy, particularly statins, appear to be the most effective of the
      therapeutic approaches, but even with their use, cardiovascular disease event
      rates remain relatively high, underpinning the quest for novel treatments. In
      this review we discuss recent advances in the field and what remains to be done
      to reduce this rate further. In particular, in addition to development and
      investigation of new LDL-cholesterol lowering therapies, there has been a major
      focus on treatments to favorably influence high-density lipoprotein (HDL)
      cholesterol and triglyceride concentrations. However, to this time, approaches to
      the latter have been somewhat disappointing, but they may have particular
      benefits in people with diabetes. As atherosclerosis is a largely preventable
      process, which is driven particularly by behavioral and lifestyle factors,
      attention to other modifiable risk factors is imperative. 

PMID- 24669299
TI  - Recent advances in the medical treatment of Cushing's disease.
AB  - Cushing's disease is a condition of hypercortisolism caused by an
      adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. While rare, it is
      associated with significant morbidity and mortality, which suggests that early
      and aggressive intervention is required. The primary, definitive therapy for
      patients with Cushing's disease in the majority of patients is pituitary surgery,
      generally performed via a transsphenoidal approach. However, many patients will
      not achieve remission or they will have recurrences. The consequences of
      persistent hypercortisolism are severe and, as such, early identification of
      those patients at risk of treatment failure is exigent. Medical management of
      Cushing's disease patients plays an important role in achieving long-term
      remission after failed transsphenoidal surgery, while awaiting effects of
      radiation or before surgery to decrease the hypercortisolemia and potentially
      reducing perioperative complications and improving outcome. Medical therapies
      include centrally acting agents, adrenal steroidogenesis inhibitors and
      glucocorticoid receptor blockers. Furthermore, several new agents are in clinical
      trials. To normalize the devastating disease effects of hypercortisolemia, it is
      paramount that successful patient disease management includes individualized,
      multidisciplinary care, with close collaboration between endocrinologists,
      neurosurgeons, radiation oncologists, and general surgeons. This commentary will
      focus on recent advances in the medical treatment of Cushing's, with a focus on
      newly approved ACTH modulators and glucocorticoid receptor blockers. 

PMID- 24669300
TI  - Therapeutic potential of atmospheric neutrons.
AB  - BACKGROUND: Glioblastoma multiform (GBM) is the most common and most aggressive
      type of primary brain tumour in humans. It has a very poor prognosis despite
      multi-modality treatments consisting of open craniotomy with surgical resection,
      followed by chemotherapy and/or radiotherapy. Recently, a new treatment has been
      proposed - Boron Neutron Capture Therapy (BNCT) - which exploits the interaction
      between Boron-10 atoms (introduced by vector molecules) and low energy neutrons
      produced by giant accelerators or nuclear reactors. METHODS: The objective of the
      present study is to compute the deposited dose using a natural source of neutrons
      (atmospheric neutrons). For this purpose, Monte Carlo computer simulations were
      carried out to estimate the dosimetric effects of a natural source of neutrons in
      the matter, to establish if atmospheric neutrons interact with vector molecules
      containing Boron-10. RESULTS: The doses produced (an average of 1 MUGy in a 1 g
      tumour) are not sufficient for therapeutic treatment of in situ tumours. However,
      the non-localised yet specific dosimetric properties of 10B vector molecules
      could prove interesting for the treatment of micro-metastases or as (neo)adjuvant
      treatment. On a cellular scale, the deposited dose is approximately 0.5
      Gy/neutron impact. CONCLUSION: It has been shown that BNCT may be used with a
      natural source of neutrons, and may potentially be useful for the treatment of
      micro-metastases. The atmospheric neutron flux is much lower than that utilized
      during standard NBCT. However the purpose of the proposed study is not to replace
      the ordinary NBCT but to test if naturally occurring atmospheric neutrons,
      considered to be an ionizing pollution at the Earth's surface, can be used in the
      treatment of a disease such as cancer. To finalize this study, it is necessary to
      quantify the biological effects of the physically deposited dose, taking into
      account the characteristics of the incident particles (alpha particle and Lithium
      atom) and radio-induced effects (by-stander and low dose effect). One of the aims
      of the presented paper is to propose to experimental teams (which would be
      interested in studying the phenomena) a simple way to calculate the dose
      deposition (allometric fit of free path, transmission factor of brain).

PMID- 24669301
TI  - The next generation of radiation oncologists: Challenges and perspectives.

PMID- 24669302
TI  - Role of modern radiation therapy in early stage Hodgkin's lymphoma: A young
      radiation oncologists' perspective.
AB  - The role of radiotherapy is well established in combined modality programs for
      early stage Hodgkin's lymphoma, but still debated with regards to late toxicity
      issues. Modern radiotherapy prescribing attitudes include lower doses and smaller
      fields, together with the implementation of sophisticated and dedicated delivery
      techniques. Aim of this review is to briefly discuss the current role of
      radiotherapy in this field and the potential future developments. Major trials
      conducted in recent years in early stage Hodgkin's lymphoma are critically
      reviewed and discussed with a focus on radiotherapy-related issues and with an
      attention to current treatment options by a "young" radiation oncologists'
      perspective. 

PMID- 24669303
TI  - New perspectives in radiation oncology: Young radiation oncologist point of view
      and challenges.
AB  - AIM: To assess the role of the young radiation oncologist in the context of
      important recent advancements in the field of radiation oncology, and to explore
      new perspectives and competencies of the young radiation oncologist. BACKGROUND:
      Radiation oncology is a field that has rapidly advanced over the last century. It
      holds a rich tradition of clinical care and evidence-based practice, and more
      recently has advanced with revolutionary innovations in technology and computer
      science, as well as pharmacology and molecular biology. MATERIALS AND METHODS:
      Several young radiation oncologists from different countries evaluated the
      current status and future directions of radiation oncology. RESULTS: For young
      radiation oncologists, it is important to reflect on the current practice and
      future directions of the specialty as it relates to the role of the radiation
      oncologist in the comprehensive management of cancer patients. Radiation
      oncologists are responsible for the radiation treatment provided to patients and
      its subsequent impact on patients' quality of life. Young radiation oncologists
      must proactively master new clinical, biological and technical information, as
      well as lead radiation oncology teams consisting of physicists, dosimetrists,
      nurses and technicians. CONCLUSIONS: The role of the young radiation oncologist
      in the field of oncology should be proactive in developing new competencies.
      Above all, it is important to remember that we are dealing with the family
      members and loved ones of many individuals during the most difficult part of
      their lives.

PMID- 24669304
TI  - The French Society of Young Radiation Oncologists: History, goals and
      perspective.
AB  - The SFjRO was created ten years ago to promote radiation oncology teaching in
      France. Our society has now more than 120 members from all around the country.
      Each year, two national courses are organized where all members are invited. 

PMID- 24669305
TI  - A strategy for young members within national radiation oncology societies: the
      Italian experience (AIRO Giovani group).
AB  - AIM: To briefly review history, structure, past events and future projects of
      AIRO (Associazione Italiana Radioterapia Oncologica) young group (AIRO Giovani),
      focusing on its specific commitment to multidisciplnary networking among junior
      clinical oncologists at a national and international level. BACKGROUND: AIRO
      Giovani is a part of AIRO composed by members under 40 years old. Its main
      activities are scientific and educational meetings dedicated to young Italian
      radiation oncologists and collaborative research projects. MATERIALS AND METHODS:
      AIRO Giovani structure, events organized and supported by AIRO giovani as well as
      scientific activities are here reported from its creation in 2007 up to current
      days. RESULTS: AIRO Giovani group was able to create a consolidated network
      between Italian junior radiation oncologists, while opening the possibility to
      collaborate with junior groups of other national scientific societies in the
      field of oncology and with ESTRO young members. Scientific projects carried out
      by the group have been successful and will be further implemented in next years.
      CONCLUSIONS: AIRO Giovani is still in its infancy, but its early positive
      experience supports the creation and development of young groups within national
      radiation oncology societies.

PMID- 24669306
TI  - Initial experience of hypofractionated radiation retreatment with true beam and
      flattening filter free beam in selected case reports of recurrent nasopharyngeal
      carcinoma.
AB  - AIM: To show our preliminary experience in using TrueBeam with RapidArc
      technology and FFF beam for stereotactic re-irradiation of nasopharyngeal
      carcinoma. BACKGROUND: Thanks to new advanced techniques, as well as intensity
      modulated radiation therapy, it is possible to approach head and neck recurrences
      in selected patients. Volumetric Modulated Arc Therapy (VMAT) in its
      RapidArc((r)) format, permits to reduce significantly the time to deliver complex
      intensity modulated plans, allowing to treat hypofractionated regimes within a
      few minutes. With TrueBeam it is possible to perform photon beams without usage
      of the flattening filter. It seems possible to expect a reduction of out-of-field
      dose when flattening filter free (FFF) beams are used. While research into the
      physics domain for FFF beams is increasing, there are very few clinical data
      where FFF beams are applied in clinical practice. MATERIALS AND METHODS: We
      present here the cases of 4 patients with local or regional recurrence of
      nasopharyngeal carcinoma. All patients were treated using TrueBeam with RapidArc
      technology and FFF beam for stereotactic hypofractionated re-irradiation.
      RESULTS: All patients concluded SBRT and showed good tolerability. During follow
      up, complete response at imaging evaluation (PET and/or MRI) for all treated
      patients was documented. CONCLUSIONS: Our preliminary experience using TrueBeam
      with RapidArc technology and FFF beam for stereotactic hypofractionated re
      irradiation of nasopharyngeal carcinoma was safe and effective in all 4 treated
      patients. Longer follow-up and a larger population of study is needed to confirm
      these promising results.

PMID- 24669307
TI  - Detection of risk factors that influence weight loss in patients undergoing
      radiotherapy.
AB  - AIM: To identify risk factors that influence weight loss in patients receiving
      radiotherapy. BACKGROUND: It is a well-known fact that cancer patients can be
      affected by malnutrition at the onset of the disease and during treatment due to
      the toxicity. Pretreatment weight loss alone does not predict those who will need
      nutritional supplementation. Instead, a variety of nutritional and tumor related
      factors needs to be taken into account. MATERIAL AND METHODS: A retrospective
      study was conducted on 129 patients with different tumor locations. Weight loss
      was evaluated during radiotherapy and one month after treatment. The impact of
      age, ECOG, chemotherapy, pretreatment weight loss, tumor location, previous
      surgery and TNM were analyzed. We aimed to identify a high-risk group of patients
      before starting treatment. RESULTS: The average net weight loss during
      radiotherapy and one month after treatment for this group of patients was 0.68 kg
      and 1.6 kg, respectively. Median weight loss during radiotherapy was 2.6 kg for
      head and neck (HN) patients and 0.27  kg for other tumor sites (p = 0.028).
      Median weight loss one month after radiotherapy was 3.7 kg for HN patients and
      1.1 kg for the rest of the patients (p = 0.034). The median weight loss one month
      after treatment was 3.2 kg for patients receiving chemotherapy and 0.5 kg for
      those patients who did not receive chemotherapy (p < 0.001). A regression
      analysis determined that HN tumor location and the use of chemotherapy were
      independent risk factors. CONCLUSIONS: Nutritional status must be monitored and
      managed before, during and after treatment. A variety of nutritional and tumor
      related factors must be considered. According to our results, head and neck
      tumors and the use of chemotherapy are the only two factors considered
      statistically significant. Because patients continue to lose weight after
      treatment, we recommend close surveillance after radiotherapy.

PMID- 24669308
TI  - Smartphones and tablets: Reshaping radiation oncologists' lives.
AB  - BACKGROUND: Smartphones and tablets are new handheld devices always connected to
      an information source and capable of providing instant updates, they allow
      doctors to access the most updated information and provide decision support at
      the point of care. AIM: The practice of radiation oncology has always been a
      discipline that relies on advanced technology. Smartphones provide substantial
      processing power, incorporating innovative user interfaces and applications.
      MATERIALS AND METHODS: The most popular smartphone and tablet app stores were
      searched for "radiation oncology" and "oncology" related apps. A web search was
      also performed searching for smartphones, tablets, oncology, radiology and
      radiation oncology. RESULTS: Smartphones and tablets allow rapid access to
      information in the form of podcasts, apps, protocols, reference texts, recent
      research and more. CONCLUSION: With the rapidly changing advances in radiation
      oncology, the trend toward accessing resources via smartphones and tablets will
      only increase, future will show if this technology will improve clinical care.

PMID- 24669309
TI  - Quality of life and radiotherapy in brain metastasis patients.
AB  - AIM: The primary objective of this study was to assess whether there was an
      improvement in QoL for patients with brain metastases after radiotherapy
      treatments. BACKGROUND: Assessment of quality of life (QoL) in brain metastasis
      patients has become increasingly recognized as an important outcome. MATERIALS
      AND METHODS: Patients treated for brain metastasis in our department during 2010
      were included in our prospective study. QoL assessments were conducted at
      baseline, 1 month, and 3 months after completion of whole-brain radiotherapy
      (WBRT). Wilcoxon test for multiple comparisons was calculated to detect
      significant differences in global QoL scores. RESULTS: Thirty-nine patients with
      brain metastases completed the EORTC QLQ-C30/BN-20 questionnaire independently.
      Median age was 59.9 years (from 37 to 81 years). Our results report differences
      between the baseline and 3 months in worsening of a global health status (p =
      0.034) and cognitive function (p = 0.004), as well as drowsiness (p = 0.001),
      appetite loss (p = 0.031) and hair loss (p = 0.005). There is a tendency for
      deterioration of physical function (p = 0.004), communication deficit (p =
      0.012), and weakness of legs (p = 0.024), between the baseline and 1 month
      evaluation. There was no difference in a global cognitive status between
      different evaluations. Median survival time was 3 months (CI 95% 1.85; 4.15).
      CONCLUSIONS: Our findings indicate a small deterioration for a global QoL status,
      and large deterioration for cognitive function after radiation treatments, as
      well as worsening of brain metastasis related symptom items. Further research is
      necessary to refine treatment selection for patients with brain metastases, since
      it may at least contribute to the stabilization of their QoL status.

PMID- 24669310
TI  - The future of Radiation Oncology: Considerations of Young Medical Doctor.
AB  - Radiation therapy plays an increasingly important role in the management of
      cancer. Currently, more than 50% of all cancer patients can expect to receive
      radiotherapy during the course of their disease, either in a primary management
      (radical or adjuvant radiotherapy) or for symptom control (palliative
      radiotherapy). Radiation oncology is a very unique branch of medicine connected
      with clinical knowledge and also with medical physics. In recent years, this
      approach has become increasingly absorbed with technological advances. This
      increasing emphasis on technology, together with other important changes in the
      health-care economic environment, now place the specialty of radiation oncology
      in a precarious position. New treatment technologies are evolving at a rate
      unprecedented in radiation therapy, paralleled by improvements in computer
      hardware and software. These techniques allow assessment of changes in the tumour
      volume and its location during the course of therapy (interfraction motion) so
      that re-planning can adjust for such changes in an adaptive radiotherapy process.
      If radiation oncologists become simply the guardians of a single therapeutic
      modality they may find that time marches by and, while the techniques will live
      on, the specialty may not. This article discusses these threats to the field and
      examines strategies by which we may evolve, diversify, and thrive. 

PMID- 24669311
TI  - Thermal and resonance neutrons generated by various electron and X-ray
      therapeutic beams from medical linacs installed in polish oncological centers.
AB  - BACKGROUND: High-energy photon and electron therapeutic beams generated in
      medical linear accelerators can cause the electronuclear and photonuclear
      reactions in which neutrons with a broad energy spectrum are produced. A low
      energy component of this neutron radiation induces simple capture reactions from
      which various radioisotopes originate and in which the radioactivity of a linac
      head and various objects in the treatment room appear. AIM: The aim of this paper
      is to present the results of the thermal/resonance neutron fluence measurements
      during therapeutic beam emission and exemplary spectra of gamma radiation emitted
      by medical linac components activated in neutron reactions for four X-ray beams
      and for four electron beams generated by various manufacturers' accelerators
      installed in typical concrete bunkers in Polish oncological centers. MATERIALS
      AND METHODS: The measurements of neutron fluence were performed with the use of
      the induced activity method, whereas the spectra of gamma radiation from decays
      of the resulting radioisotopes were measured by means of a portable high-purity
      germanium detector set for field spectroscopy. RESULTS: The fluence of thermal
      neutrons as well as resonance neutrons connected with the emission of a 20 MV X
      ray beam is ~10(6) neutrons/cm(2) per 1 Gy of a dose in water at a reference
      depth. It is about one order of magnitude greater than that for the 15 MV X-ray
      beams and about two orders of magnitude greater than for the 18-22 MeV electron
      beams regardless of the type of an accelerator. CONCLUSION: The thermal as well
      as resonance neutron fluence depends strongly on the type and the nominal
      potential of a therapeutic beam. It is greater for X-ray beams than for
      electrons. The accelerator accessories and other large objects should not be
      stored in a treatment room during high-energy therapeutic beam emission to avoid
      their activation caused by thermal and resonance neutrons. Half-lives of the
      radioisotopes originating from the simple capture reaction (n,gamma) (from
      minutes to hours) are long enough to accumulate radioactivity of components of
      the accelerator head. The radiation emitted by induced radioisotopes causes the
      additional doses to staff operating the accelerators.

PMID- 24669312
TI  - Joint effects of physical activity and BMI on risk of hypertension in women: a
      longitudinal study.
AB  - INTRODUCTION: There is debate as to whether physical activity counteracts the
      adverse effect of weight on health outcomes. We investigated how physical
      activity modifies the effect of body mass index (BMI) on hypertension risk.
      METHODS: BMI, physical activity, and hypertension were measured at baseline and
      at three-year interval for 14 years (from 1996 to 2010), in 10,339 participants
      in the Australian Longitudinal Study on Women's Health. Generalised estimating
      equation models for binary repeated measures were performed to determine the
      individual and joint effects of BMI and physical activity on incident
      hypertension. RESULTS: At baseline (mean age 47.6 +/- 1.5 SD), 57% were healthy
      weight, 28% overweight, and 14% obese. Increasing BMI and decreasing physical
      activity were associated with increased risk of hypertension. Physical activity
      attenuated the positive association between weight and risk of hypertension,
      especially for obese women. Compared to healthy weight high active women, risk of
      hypertension in obese high active women was 3.4 times greater (OR 3.43, 95% CI
      2.68, 4.39) and in obese inactive women 4.9 times greater (OR 4.91, 95% CI 3.92,
      6.13). CONCLUSIONS: Both physical activity and maintenance of a healthy body
      weight are associated with lower risk of hypertension. Physical activity reduced
      but did not remove the effect of obesity on hypertension risk.

PMID- 24669313
TI  - Predicting increased blood pressure using machine learning.
AB  - The present study investigates the prediction of increased blood pressure by body
      mass index (BMI), waist (WC) and hip circumference (HC), and waist hip ratio
      (WHR) using a machine learning technique named classification tree. Data were
      collected from 400 college students (56.3% women) from 16 to 63 years old.
      Fifteen trees were calculated in the training group for each sex, using different
      numbers and combinations of predictors. The result shows that for women BMI, WC,
      and WHR are the combination that produces the best prediction, since it has the
      lowest deviance (87.42), misclassification (.19), and the higher pseudo R (2)
      (.43). This model presented a sensitivity of 80.86% and specificity of 81.22% in
      the training set and, respectively, 45.65% and 65.15% in the test sample. For men
      BMI, WC, HC, and WHC showed the best prediction with the lowest deviance (57.25),
      misclassification (.16), and the higher pseudo R (2) (.46). This model had a
      sensitivity of 72% and specificity of 86.25% in the training set and,
      respectively, 58.38% and 69.70% in the test set. Finally, the result from the
      classification tree analysis was compared with traditional logistic regression,
      indicating that the former outperformed the latter in terms of predictive power. 

PMID- 24669314
TI  - Continuous exercise but not high intensity interval training improves fat
      distribution in overweight adults.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of high intensity
      interval training (HIIT) versus continuous aerobic exercise training (CONT) or
      placebo (PLA) on body composition by randomized controlled design. METHODS: Work
      capacity and body composition (dual-energy X-ray absorptiometry) were measured
      before and after 12 weeks of intervention in 38 previously inactive overweight
      adults. RESULTS: There was a significant group * time interaction for change in
      work capacity (P < 0.001), which increased significantly in CONT (23.8 +/- 3.0%)
      and HIIT (22.3 +/- 3.5%) but not PLA (3.1 +/- 5.0%). There was a near-significant
      main effect for percentage trunk fat, with trunk fat reducing in CONT by 3.1 +/-
      1.6% and in PLA by 1.1 +/- 0.4%, but not in HIIT (increase of 0.7 +/- 1.0%) (P =
      0.07). There was a significant reduction in android fat percentage in CONT (2.7
      +/- 1.3%) and PLA (1.4 +/- 0.8%) but not HIIT (increase of 0.8 +/- 0.7%) (P =
      0.04). CONCLUSION: These data suggest that HIIT may be advocated as a time
      efficient strategy for eliciting comparable fitness benefits to traditional
      continuous exercise in inactive, overweight adults. However, in this population
      HIIT does not confer the same benefit to body fat levels as continuous exercise
      training.

PMID- 24669315
TI  - Evaluation of Beneficial Metabolic Effects of Berries in High-Fat Fed C57BL/6J
      Mice.
AB  - Objective. The aim of the study was to screen eight species of berries for their
      ability to prevent obesity and metabolic abnormalities associated with type 2
      diabetes. Methods. C57BL/6J mice were assigned the following diets for 13 weeks:
      low-fat diet, high-fat diet or high-fat diet supplemented (20%) with lingonberry,
      blackcurrant, bilberry, raspberry, acai, crowberry, prune or blackberry. Results.
      The groups receiving a high-fat diet supplemented with lingonberries,
      blackcurrants, raspberries or bilberries gained less weight and had lower fasting
      insulin levels than the control group receiving high-fat diet without berries.
      Lingonberries, and also blackcurrants and bilberries, significantly decreased
      body fat content, hepatic lipid accumulation, and plasma levels of the
      inflammatory marker PAI-1, as well as mediated positive effects on glucose
      homeostasis. The group receiving acai displayed increased weight gain and
      developed large, steatotic livers. Quercetin glycosides were detected in the
      lingonberry and the blackcurrant diets. Conclusion. Lingonberries were shown to
      fully or partially prevent the detrimental metabolic effects induced by high-fat
      diet. Blackcurrants and bilberries had similar properties, but to a lower degree.
      We propose that the beneficial metabolic effects of lingonberries could be useful
      in preventing obesity and related disorders. 

PMID- 24669316
TI  - Nutritional knowledge and attitudes of adolescent swimmers in trinidad and
      tobago.
AB  - Purpose. To investigate the level of nutrition knowledge and attitude of
      adolescent male and female swimmers training competitively in Trinidad and
      Tobago. Methodology. A self-administered questionnaire, which consisted of 21
      nutrition knowledge and 11 attitude statements, was utilized to assess the level
      of nutrition knowledge and attitude of adolescent swimmers. For the assessment of
      nutrition knowledge, correct answers were given a score of "1" and incorrect
      answers were given a score of "0." For the evaluation of attitude towards
      nutrition, a score ranging from 1 to 5 was assigned to each response; "5" was
      given to the most positive response, and "1" was given to the most negative. Data
      were analyzed using SPSS version 21.0. Results. Two hundred and twenty swimmers
      with a mean age of 14.56 +/- 2.544 completed the questionnaire. The mean
      nutrition knowledge score was 10.97 +/- 2.897 and mean attitude score was 41.69
      +/- 6.215. Nutrition knowledge was positively and significantly related to the
      number of reported nutrition sources (r = 0.172, P = 0.005). Nutrition knowledge
      was positively and significantly related to the attitude (r = 0.130, P = 0.027).
      Conclusions and Implication. Athletes lack nutrition knowledge but have a
      positive attitude towards nutrition, which may indicate receptiveness to future
      nutrition education. 

PMID- 24669317
TI  - Prevalence and Predictors of Maternal Anemia during Pregnancy in Gondar,
      Northwest Ethiopia: An Institutional Based Cross-Sectional Study.
AB  - Background. Anaemia is a global public health problem which has an eminence
      impact on pregnant mother. The aim of this study was to assess the prevalence and
      predictors of maternal anemia. Method. A cross-sectional study was conducted from
      March 1 to April 30, 2012, on 302 pregnant women who attended antenatal care at
      Gondar University Hospital. Interview-based questionnaire, clinical history, and
      laboratory tests were used to obtain data. Bivariate and multivariate logistic
      regression was used to identify predictors. Result. The prevalence of anemia was
      16.6%. Majority were mild type (64%) and morphologically normocytic normochromic
      (76%) anemia. Anemia was high at third trimester (18.9%). Low family income (AOR
      [95% CI] = 3.1 [1.19, 8.33]), large family size (AOR [95% CI] = 4.14 [4.13,
      10.52]), hookworm infection (AOR [95% CI] = 2.72 [1.04, 7.25]), and HIV infection
      (AOR [95% CI] = 5.75 [2.40, 13.69]) were independent predictors of anemia.
      Conclusion. The prevalence of anemia was high; mild type and normocytic
      normochromic anemia was dominant. Low income, large family size, hookworm
      infection, and HIV infection were associated with anemia. Hence, efforts should
      be made for early diagnosis and management of HIV and hookworm infection with
      special emphasis on those having low income and large family size. 

PMID- 24669318
TI  - The Relationship between Negative Affect and Reported Cognitive Failures.
AB  - The purpose of this study was to expand our understanding of the range of
      negative affect associated with reported problems with everyday functions and
      activities, measured by the cognitive failures questionnaire (CFQ). Evidence from
      previous research indicates that individuals meeting criteria for mood disorders,
      such as major depression or seasonal affective disorder, experience cognitive
      deficits in memory and attention that can lead to problems with everyday
      activities reported in the CFQ. The Positive and Negative Affect Scale (PANAS)
      was used to assess potential correlations with a wider range of negative
      emotions. Findings for a sample of 129 college students revealed that negative
      affective experiences were significantly correlated with failures of memory and
      attention on the CFQ (fear = .41, hostility = .38, sadness = .28, and guilt =
      .43). Conversely, positive affect was negatively correlated with distractibility
      (r = -.21). Additional affective scales on the PANAS (e.g., shyness and fatigue)
      were also associated with higher reports of cognitive failures. The results
      provide converging evidence of a relationship between negative affective
      experiences and reported frequency of problems on the cognitive failures
      questionnaire. 

PMID- 24669319
TI  - Clinical Outcomes of Tibial Components with Modular Stems Used in Primary TKA.
AB  - Due to the known potential for fretting and corrosion at modular junctions in
      orthopaedic implants, this retrospective study evaluated radiographic and
      clinical outcomes of 85 primary TKA patients implanted with modular stemmed
      tibial components and followed up for an average of 82 months. There was low
      incidence of tibial radiolucent lines, excellent functional outcomes, and no
      complications associated with stem modularity. The findings were comparable to
      the historical control study involving 107 TKA with a nonmodular tibial stem
      design. When using surface cemented tibial components combined with a constrained
      polyethylene bearing, modular stems appear to be a viable option for primary TKA
      when adequate fixation and rotational stability are maintained. 

PMID- 24669320
TI  - Changes in Joint Gap Balances between Intra- and Postoperation in Total Knee
      Arthroplasty.
AB  - Achieving correct soft tissue balance and preparing equal and rectangular
      extension and flexion joint gaps are crucial goals of TKA. Intraoperative gap
      balances would change postoperatively; however, changes in joint gap balances
      between pre- and postoperation remain unclear. To explore these changes
      associated with TKA, we prospectively investigated 21 posterior cruciate ligament
      retaining TKAs for varus knees. Intraoperative extension gap balance (iEGB) was
      2.6 +/- 2.0 degrees  varus versus postoperative extension gap balance (pEGB) of
      0.77 +/- 1.8 degrees  valgus (P < 0.01), while no significant difference between
      intraoperative flexion gap balance (iFGB) and postoperative flexion gap balance
      (pFGB) was observed. We also explored correlations between intraoperative and
      postoperative gap balances but found no significant correlations. These
      observations indicate that (i) surgeons should avoid excessive release of the
      medial soft tissue during TKA for varus knees and (ii) intraoperative gap balance
      may not be necessarily reflected on postoperative gap balance. 

PMID- 24669321
TI  - Carbon black particle exhibits size dependent toxicity in human monocytes.
AB  - Increased levels of particulate air pollution are associated with increased
      respiratory and cardiovascular mortality and morbidity. Some epidemiologic and
      toxicological researches suggest ultrafine particles (<100 nm) to be more harmful
      per unit mass than larger particles. In the present study, the effect of particle
      size (nano and micro) of carbon black (CB) particle on viability, phagocytosis,
      cytokine induction, and DNA damage in human monocytes, THP-1 cells, was analysed.
      The cells were incubated with nanosize (~50 nm) and micron (~500 nm) size of CB
      particles in a concentration range of 50-800 ug/mL. The parameters like MTT
      assay, phagocytosis assay, ELISA, gene expression, and DNA analysis were studied.
      Exposure to nano- and micron-sized CB particles showed size- and concentration
      dependent decrease in cell viability and significant increase in proinflammatory
      cytokines IL-1 beta , TNF- alpha and IL-6 as well as chemokine IL-8 release. Gene
      expression study showed upregulation of monocyte chemoattractant protein-1 gene
      while cyclooxygenase-2 gene remained unaffected. Nano CB particles altered the
      phagocytic capacity of monocytes although micron CB had no significant effect. CB
      particles did not show any significant effect on DNA of monocytes. The
      investigations indicate that CB particles in nanosize exhibit higher propensity
      of inducing cytotoxicity, inflammation, and altered phagocytosis in human
      monocytes than their micron size. 

PMID- 24669322
TI  - Measles epidemic in pakistan: in search of solutions.

PMID- 24669323
TI  - The Influence of Psychological Factors in Meniere's Disease.
AB  - Many physicians have observed that psychological factors play a significant role
      in the course of Meniere's disease (MD), with Meniere's patients being subject to
      anxiety and tension states. A lot of research attentions from a psychological
      point of view have been directed at MD, with earlier researchers focusing on
      psychosomatic causes of the illness as well as its somatopsychic result. However,
      the question whether MD is caused by psychological factors or whether the
      psychological manifestation in MD is as a result of the illness is still
      unresolved. The aim of this study is to provide an overview of interaction that
      exists between physical and emotional factors in the development of MD and its
      impact on the quality of life of the sufferers. A structured literature search
      was carried out, with no restrictions to the dates searched. A vicious circle of
      interaction seems to exist between the somatic organic symptoms of MD and
      resultant psychological stress. The frightening attacks of vertigo seem likely to
      produce and increase the level of anxiety thereby worsening the emotional state
      and the resultant anxiety provokes various symptoms probably through disorders of
      the autonomic nervous system occasioned by the increased levels of stress-related
      hormones. 

PMID- 24669324
TI  - Maternal and fetal Acid-base chemistry: a major determinant of perinatal outcome.
AB  - Very small changes in pH may significantly affect the function of various fetal
      organ systems, such as the central nervous system, and the cardiovascular system
      with associated fetal distress and poor Apgar score. Review of existing data on
      maternal-fetal acid-base balance in pregnancy highlight the factors that are
      associated with derangements of the acid-base status and the impact of the
      derangements on fetal outcome. Extensive search of electronic databases and
      manual search of journals for relevant literature on maternal and fetal acid
      chemistry, clinical studies and case studies were undertaken. There is a
      substantial reduction in the partial pressure of carbon dioxide (pCO2) in
      pregnancy. Adequate buffering prevents significant changes in maternal arterial
      pH. Normal fetal metabolism results in the production of acids which are buffered
      to maintain extracellular pH within a critical range. Fetal hypoxia can occur
      when maternal oxygenation is compromised, maternal perfusion of the placenta is
      reduced, or delivery of oxygenated blood from the placenta to the fetus is
      impeded. When adequate fetal oxygenation does not occur, metabolisms proceed
      along with an anaerobic pathway with production of organic acids, such as lactic
      acid. Accumulation of lactic acid can deplete the buffer system and result in
      metabolic acidosis with associated low fetal pH, fetal distress and poor Apgar
      score. There is a significant reduction in pCO2 in pregnancy. This change,
      however, does not result in a corresponding significant reduction in maternal
      arterial pH, because of adequate buffering. Very small changes in pH may cause
      significant derangement in fetal function and outcome. 

PMID- 24669325
TI  - Summer appendicitis.
AB  - Acute appendicitis has been reported to be present throughout the year, but some
      particular months are associated with higher incidences. The aim of this study
      was designed to review previous studies and analyze the current knowledge and
      controversies related to seasonal variability of acute appendicitis, to examine
      whether appendicitis has an annual seasonal pattern. A search of the MEDLINE
      databases for English language publications over the period from 1970 to 2012 was
      conducted. This list was extended by including also references from a recent
      review of appendicitis epidemiology. We selected the studies, which were
      published in an English-language peer-reviewed journal, did not have
      intervention, were conducted for at least one year and had the outcome of
      histologically-confirmed appendicitis and those which reported case data
      temporally. A total of 30 titles and abstracts were screened for eligibility. Of
      these, 11 studies from 8 countries conducted across from 1970 to 2012 met the
      selection criteria and contributed to the systematic review. A seasonal pattern
      of appendicitis with a mostly predominant peak is seen during the summer months
      in all the countries (except Nigeria and Turkey). Appendicitis is more common in
      summer months. The existence of a seasonal pattern in the onset of appendicitis
      may be due to exposure to air pollution, decreasing fiber diet and increase in
      the incidence of gastrointestinal infections in summer. 

PMID- 24669326
TI  - An overview of history, pathogenesis and treatment of perforated peptic ulcer
      disease with evaluation of prognostic scoring in adults.
AB  - Peptic ulcer disease including both gastric and duodenal ulcer form a substantial
      part of patients seeking surgical opinion world-wide. The concept of acid in
      peptic ulcer disease, which was the basis of treatment of peptic ulcer was
      revolutionized by the discovery of H2-receptor antagonists, that led to the
      principle of acid suppression therapy for duodenal ulcer which followed decades
      of preference for surgical interventions in the form of gastric resections,
      vagotomy etc., After the discovery of Helicobacter pylori organism as the
      causative factor a triple drug regime was identified to treat peptic disease
      which was further modified to sequential therapy to avoid antibiotic resistance.
      This recognition has not concluded the chapter on peptic ulcers. The management
      of ulcer disease and its complications remain a surgical challenge. All the
      materials for this review have been accessed from various internet search
      engines. The references have been narrowed down to 34 by excluding cross
      references, duplicated citations, pediatric studies, case reports, iatrogenic and
      malignant perforations and including microbiological, immunohistochemistry
      references and studies with more than a sample size of ten. Case control, cohort
      studies, prospective/retrospective, metaanalytical studies were preferred in that
      order. This article attempts to take an overview of all aspects of the management
      of peptic ulcer. 

PMID- 24669327
TI  - Retained foreign bodies: a serious threat in the Indian operation room.
AB  - Retained foreign bodies (RFBs) are a surgical complication resulting from foreign
      materials accidently left in a patient's body. This review attempts to give an
      overview of different types of RFBs, problems related to them and their
      management after the surgical operation. The internet was searched using the
      Google and Google scholar. In addition, relevant electronic journals from the
      University's library such as Entrez (including PubMed and PubMed central), Since
      Direct, Scirus, NIH.gov, Medknow.com, Medscape.com, Scopus, MedHelp.org, Cochrane
      library, WebMD.com, and World Health Organization Hinari. It shows that the major
      reasons of RFBs are emergency surgical operation with unplanned changes, patient
      high body mass index, and poor communication. To prevent this textile material
      should be radiopaque marked and must be counted once at the start and twice at
      the conclusion of all surgical procedures. If the count is incorrect, then
      radiography or manually re-exploration should be performed. Ultrasonography,
      computerized tomography, magnetic resonance imaging and radio frequency
      identification are also used in the proper identification of RFBs. Safety
      practice should be robust and simple enough to protect patient under the most
      chaotic of circumstances. Proper communication among the personnel participating
      in surgery aimed at preventing this medical negligence would help in mitigating
      such errors. Finally, the surgeon should not only follow the standard recommended
      procedure, but also report cases of RFBs. 

PMID- 24669328
TI  - A comparative study of nutritional status and foodstuffs in adolescent girls in
      iran.
AB  - BACKGROUND: The prevalence of obesity and overweight in children and adolescents
      is increasing world-wide. Obesity in children and adolescents is a major risk
      factor for diabetes, heart diseases, hypertension, and cancer in adulthood. AIM:
      The aim of the study was to compare the nutritional status and food-stuffs among
      high-school girls in Arak, Iran, in matter of body mass index (BMI) and
      associated factors. SUBJECTS AND METHODS: A cross-sectional survey of a
      representative sample of 278 adolescents was conducted in six randomly chosen
      high-schools. Height and weight of students were collected using standard methods
      and the BMI calculated and BMI percentiles of these girls are compared with the
      Center of Disease Control and Prevention (CDC) reference data. The 5(th), 8(th),
      and 95(th) percentiles of the CDC were adopted as cut-off points for underweight,
      overweight and obese girls, respectively. Data were analyzed using SPSS by
      analysis of variance and Chi-square tests. RESULTS: On the basis of CDC, the
      overall prevalence rates of underweight, overweight, and obesity were estimated
      10.1% (28/278), 12.9% (36/278), and 1.4% (4/278), respectively. There was no
      significant difference between nutritional knowledge scores and the rate of
      physical activities in various groups. The mean age at menarche was significantly
      higher among the obese girls (P = 0.02). Consumption of ice-cream and chocolate
      was significantly higher in the obese girls group (P = 0.03). CONCLUSION:
      According to the present study, the prevalence of overweight and obesity in high
      school girls of Arak is lower than that of many other parts of Iran and some
      neighboring countries, which are at the high-risk of overweight and obesity. This
      study warrants the necessity of paying attention to promote healthy life-style
      and weight control. The earlier age of menarche is alarming.

PMID- 24669329
TI  - Fine needle aspiration cytology in pediatric age group with special reference to
      pediatric tumors: a retrospective study evaluating its diagnostic role and
      efficacy.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) is a well-established
      diagnostic technique in adult mass lesions but a comparatively new technique to
      pediatric lesions. AIM: The current study aims to evaluate the role of FNAC in
      pediatric age with special reference to pediatric tumors. SUBJECTS AND METHODS: A
      retrospective study of FNAC in children <= 18 years of age presenting with mass
      lesions was studied for 5 years. Distribution of cases in different age groups,
      sex, and site of lesion was analyzed. Pediatric lesions were categorized into non
      neoplastic, benign, and malignant conditions. Diagnostic efficacy was assessed by
      comparing subsequent histopathological examination wherever possible. STATISTICAL
      ANALYSIS: Epi info 07 (Centers for Disease Control and Prevention in Atlanta,
      Georgia (USA) 07) and values were presented as simple percentages. RESULTS: FNAC
      was performed on 2903 cases in 5 years out of which 327 cases 11.3% (327/2903)
      were <= 18 years of age. Out of 327 cases, 180 cases 55% (180/327) were between
      11 and 18 years. Male to female ratio was 1.15:1. The commonest site for FNAC was
      cervical lymph node swelling 48.3% (158/327). Reactive lymphadenitis was the
      commonest diagnosis among all mass lesions 38.8% (103/265), whereas Fibroadenoma
      20.8% (10/49) was commonest diagnosis among benign lesions and among malignant
      lesions there were two cases 15.3% (2/13) each of Hodgkins and non-Hodgkins
      lymphoma and one case of chondrosarcoma. The positive predictive value of
      diagnosing malignant lesions on FNAC was 100%. CONCLUSIONS: The ease of FNAC
      along with its high diagnostic accuracy makes it a desirable method for
      diagnosing lesions in children.

PMID- 24669330
TI  - An audit of laparoscopic cholecystectomy in renal transplant patients.
AB  - BACKGROUND: Choleliathisis, in patients with renal transplantation, carries high
      risk of complications. We, at our institute, perform prophylactic cholecystectomy
      for aymptomatic gallstones in patients with renal transplantation. AIM: To
      present our experience of laparoscopic cholecystectomy in patients with kidney
      transplantation. SUBJECTS AND METHODS: Data, in the form of, demographics,
      medications used, indication of transplantation, manifestation of gallstones,
      operative findings, duration of hospitalization, and post-operative complications
      were obtained and results were analyzed. briefly summarize details of statistics
      including the soft ware used. RESULTS: Twenty patients have undergone
      laparoscopic cholecystectomy. All patients were admitted on the day of surgery.
      Immunosuppression regimen was not modified during hospitalization. Indications of
      cholecystectomy were biliary colic (8/20 patients, 40%), acute cholecystitis
      (8/20 patients, 40%), asymptomatic gallstones (3/20 patients, 15%), and
      obstructive jaundice (1/20 patients, 5%). Laparoscopic cholecystectomy was
      uneventful in all cases. Post-operative complications were nausea and vomiting in
      two patients and port site infection in one patient. CONCLUSION: Laparoscopic
      cholecystectomy, when performed in renal transplant patients, is a safe
      procedure.

PMID- 24669331
TI  - Hospital and Community Isolates of Uropathogens and their Antibiotic Sensitivity
      Pattern from a Tertiary Care Hospital in North West India.
AB  - BACKGROUND: Urinary tract infection remains one of the most common infections,
      both in the community and in the hospital. The causative pathogen profile varies
      from region to region, but Escherichia coli (E. coli) remains the most common
      causative pathogen. The sensitivity of uropathogens to different drugs varies in
      different areas, and changes with time. This necessitates periodic studies of the
      causative uropathogens and their antibiotic sensitivity pattern. AIM: To
      investigate the profile of common uropathogens and assess their antibiotic
      sensitivity patterns to commonly used antimicrobial agents. MATERIALS AND
      METHODS: Analysis of all urine specimens submitted for culture and sensitivity
      was carried out over a 1-year period in a tertiary care hospital in North West
      India. Urine culture was done by a semi-quantitative method. Antibiotic
      sensitivity was done on bacterial isolates according to the Clinical and
      Laboratory Standards Institute CLSI guidelines for disc diffusion susceptibility
      test. Data was analysed for significance using Chi square test. RESULTS: Of a
      total of 6348 urine specimens received over the 1-year study period, 41.8% (2653)
      of the urine samples were culture positive. The most common bacterial isolate was
      E. coli (45.7%, 1103/2412), followed by Coagulase-negative Staphylococci (18.6%,
      449/2412) and Klebsiella species (8.3%, 199/2412). The Candida species' isolation
      rate was 10.3% (277/2689). The uropathogens displayed a very high level of
      resistance to fluroquinolones 70.3% (1084/1542)[Inpatient Department (IPD) -
      70.5%(572/812), Outpatient Department (OPD) - 70.2%(512/730)] and cephalosporins
      75.1%(1158/1542)[IPD - 73.8%(599/812), OPD - 76.6%(559/730)], whereas resistance
      to nitrofurantoin 19.8%(305/1542) [ IPD - 23.9%, OPD - 15.2%(111/730)], amikacin
      32.4%(573/1769) [IPD - 36.1%(235/934), OPD - 28.1%(235/835)] and cephoperazone +
      sulbactam combination 22%(349/1583) [IPD - 26.2%(244/914), OPD - 15.8%(105/669)]
      was low. CONCLUSION: Empiric selection of antimicrobial agents should be based on
      the antibiotic sensitivity pattern of the uropathogens prevalent in that area,
      which is derived from epidemiological studies carried out in that environment.

PMID- 24669332
TI  - Utilization of teeth replacement service among the elderly attending teaching
      hospitals in lagos, Nigeria.
AB  - BACKGROUND: Tooth replacement service is generally available in our environment.
      However, its utilization by the elderly has not been extensively studied. AIM: To
      determine the utilization of tooth replacement services among the elderly.
      MATERIALS AND METHODS: This was a retrospective study of 440 patients aged 60
      years and above attending the prosthetic out-patient clinics of Lagos University
      teaching hospital (LUTH) and Lagos state University teaching hospital (LASUTH)
      from January, 2008 to March, 2010. record books or case records: Age, sex, and
      number of teeth replaced. Results were collated and analyzed using Epi Info 2004.
      Values were presented as simple percentages. RESULTS: There were 229/440 (52.0%)
      males and 211/440 (48.0%) females and were aged 60-90 years with a mean age of
      68.9 (6.92). A total number of 4,062 teeth were replaced. Average number of tooth
      replaced among the patients was 9.45 for LUTH and 8.94 for LASUTH. The maxillary
      anterior teeth were the most frequently replaced 1422/4062 (35.0%) and the least
      replaced were the mandibular posterior teeth 812/4062 (20.0%). The average number
      of tooth replaced generally increased with age in both sexes. A total of 90
      complete maxillary and mandibular dentures were fabricated, while six single arch
      complete dentures were made. The remaining were partial dentures. CONCLUSION: The
      most common age of presentation is 60-65 years. Patients that were 90 years and
      above appear to utilize teeth replacement facilities in this environment less
      than those in developed countries. Maxillary anterior teeth were the most
      frequently replaced.

PMID- 24669333
TI  - Constraints, challenges and prospects of public-private partnership in health
      care delivery in a developing economy.
AB  - BACKGROUND: In Nigeria, concerns on the quality and financing of health-care
      delivery especially in the public sector have initiated reforms including support
      for public-private partnerships (PPP) at the Federal Ministry of Health.
      Likewise, Enugu State has developed a draft policy on PPP since 2005. However,
      non-validation and non-implementation of this policy might have led to loss of
      interest in the partnership. AIM: The aim of this study was to provide evidence
      for planning the implementation of PPP in Enugu State health system via a multi
      sectoral identification of challenges, constraints and prospects. SUBJECTS AND
      METHODS: Pre-tested questionnaires were administered to 466 respondents (251
      health workers and 215 community members), selected by multi-stage sampling
      method from nine Local Government Areas of Enugu State, Nigeria, over a study
      period of April 2011 to September 2011. Data from the questionnaires were
      collated manually and quantitative data analyzed using SPSS version 15 (Chicago,
      IL, USA). RESULTS: Only 159 (34.1%, 159/466) of all respondents actually
      understood the meaning of PPP though 251 (53.9%) of them had claimed knowledge of
      the concept. This actual understanding was higher among health workers (57.8%,
      145/251) when compared with the community members (6.5%, 14/215) (P < 0.001).
      Post-PPP enlightenment reviews showed a more desire for PPP implementation among
      private health-care workers (89.4%, 101/113) and community leaders/members
      (55.4%, 119/215). CONCLUSION: PPP in health-care delivery in Enugu State is
      feasible with massive awareness, elaborate stakeholder's engagements and well
      structured policy before implementation. A critical challenge will be to convince
      the public sector workers who are the anticipated partners to accept and support
      private sector participation.

PMID- 24669334
TI  - Evaluation of inhaler techniques among asthma patients seen in Nigeria: an
      observational cross sectional study.
AB  - BACKGROUND: An Adequate and an effective dose of inhalation drugs can be
      administered only if the correct inhaler-specific technique is followed by asthma
      patients. There is paucity of data on this subject among Nigerians and Africans.
      AIMS: This observational study was to assess the inhaler techniques among asthma
      patients in Nigeria and also to identify the factors related to an inaccurate or
      poor inhaler use. SUBJECTS AND METHODS: Consenting asthma patients on inhalers,
      who attended medical out-patients clinic, of two university hospitals in Nigeria
      were asked to use their inhalers while an inhaler-administration checklist was
      used to assess each patients inhaler technique. Information on demographics,
      asthma symptoms history and history of technique education were obtained. Data
      was analyzed using standard statistical methods. RESULTS: A total of 140 asthma
      patients participated out of which 75 were females. All the patients used
      pressurized metered dose inhalers (pMDI) type; 51 of them used dry powder
      inhalers (DPI) in addition. For pMDI, 22.1% (31/140) completed all required steps
      while 37.3% (19/51) did so for DPI (P = 0.04). Patients with higher educational
      qualification (P < 0.01) and those with less frequent asthma symptoms (P < 0.01)
      are more likely to use the pMDI inhalers more accurately while patients who have
      been taught previously by a Doctor were more likely to use the DPI better.
      CONCLUSION: Majority of asthma patients use their inhalers inaccurately. Patient
      dependent factors were identified as the cause of incorrect technique of inhaler
      use. Asthma patients on inhalation medications should have routine assessment of
      their inhaler technique at every visit and corrected if found to be poor.

PMID- 24669335
TI  - An evaluation of hepatotoxicity in breast cancer patients receiving injection
      Doxorubicin.
AB  - BACKGROUND: Hepatic dysfunction in the cancer unit has a significant impact on
      patient outcomes. The therapeutic application of anthracycline antibiotics are
      limited by side-effects mainly myelosuppression, chronic cardiotoxicity, and
      hepatotoxicity. AIM: To assess the risk of Hepatotoxicity in breast cancer
      patients receiving Inj. Doxorubicin. SUBJECTS AND METHODS: The investigation was
      a prospective study that was conducted in cancer patients receiving Inj.
      Doxorubicin doses of 50 mg/m(2), and 75 mg/m(2) at a South Indian tertiary care
      hospital. Sample collection was carried out from pre-chemotherapy to 4(th) cycle.
      Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic
      transaminase (SGPT), direct bilirubin and total bilirubin were assessed to
      determine hepatotoxicity. Data were analyzed using unpaired t-test, Pearson
      correlation using Graph-Pad Prism version 5.00 for Windows, Graph-Pad Software,
      San Diego, California, USA, www.graphpad.com. RESULTS: Breast cancer patients
      comprised 37% (49/132) of the total female cancer patient population, of which 46
      patients with a mean age of 46.6 (13.4) years were included and 30.4% (14/46)
      patients were developed hepatotoxicity. The mean standard deviation of SGOT,
      SGPT, direct bilirubin, total bilirubin in the pre-chemotherapy cycle to fourth
      chemotherapy cycle were found to be 21.97 (5.798) U/L and 181.3 (103.6) U/L,
      23.17 (6.237) U/L and 147.6 (90.9) U/L, 0.1351 (0.1186) mg/dL and 0.5445 (0.4587)
      mg/dL, 0.3094 (1.346) mg/dL and 2.7163 (1.898) mg/dL simultaneously where P <
      0.05 which were statistically significant. CONCLUSION: There exist a strong
      correlation between the use of Inj. Doxorubicin and risk for developing
      hepatotoxicity. The health-care professionals dealing with breast cancer patients
      need to have awareness for hepatotoxicity with the use of Inj. Doxorubicin
      therapy.

PMID- 24669336
TI  - The awareness of health professionals in diagnostic techniques for intestinal
      parasites in gaza strip, palestine.
AB  - BACKGROUND: Diagnosis of intestinal parasites still depends on conventional
      methods in Gaza strip hospitals and private laboratories. AIM: This study aimed
      to evaluate the opinion and the practice of physicians and medical laboratories
      technologists towards the diagnosis of intestinal parasites in Gaza strip.
      SUBJECTS AND METHODS: The study was carried out during the period from August
      2006 to December 2006. All the subjects during this period were eligible for the
      interview. The sample size included 371 individuals out of them 270 physicians
      and 101 medical laboratory technologists (MLTs). Simple random sampling was used
      to select the physicians and MLTs from eight hospitals and eleven primary health
      care centers. RESULTS: It was found that (57.8%) 156/270 of physicians depend on
      the direct smear microscopy in the diagnosis of intestinal parasites in Gaza,
      compared to (31.7% (32/101) of MLT. Knowledge about the possible correlation of
      occult blood with reasons other than the presence of intestinal parasites was
      evident among both physicians and MLTs, reaching over 80% (P = 0.08). It was
      found that (54.4%, 147/270) of physicians and (73.3%. 74/101) of MLTs depend on
      wet mount result for of Entamoeba histolytica diagnosis (P = 0.01). CONCLUSION:
      Low awareness was found among both physicians and MLT regarding the diagnostic
      techniques used in the examination of intestinal parasites in Gaza Strip.
      Prescription of medicine by physicians sometimes depends on the clinical picture
      without laboratory confirmation. Advanced techniques were less used in the
      diagnosis of intestinal parasites in Gaza strip.

PMID- 24669337
TI  - "Too Young to be Worried!" Psychiatric Assessment and Follow-up of Young People
      After Severe Physical Assault in an Inner City Hospital of South London.
AB  - BACKGROUND: Interpersonal violence amongst youth is on the rise world-wide and
      London is no exception. The resulting injuries can be very serious and even
      result in death. This is a difficult to engage subgroup of patients and there is
      likely to be significant unmet social and mental health needs. AIM: The current
      paper discusses the results of immediate psychiatric and social assessment of
      young people following a serious physical assault as assessed by a pediatric
      liaison Child and Adolescent Mental Health Service (CAMHS). CAMHS in Kings
      College Hospital, London in one calendar year and also the help seeking behavior
      of the young people following the assault. SUBJECTS AND METHODS: The Department
      of Pediatric Liaison Psychiatry is based within the Kings College Hospital and
      has a multidisciplinary team comprising of nurses, consultant child and
      adolescent psychiatrists and social workers who reviewed all patients who were
      referred to them following an episode of assault. All young people who were
      referred to the department of pediatric liaison psychiatry based within Kings
      College Hospital over one calendar year were included in the analysis. RESULTS:
      83% (29/35) of the victims were male and 83% (29/35) were from minority ethnic
      backgrounds. Although 70% (25/35) of the young people included in this study had
      significant safe guarding concerns, only 17% (6/35) turned up for their follow-up
      appointments with child mental health teams. CONCLUSIONS: Innovative models of
      service delivery are required to cater to the unique needs of this group of
      extremely vulnerable young people.

PMID- 24669338
TI  - Mass counseling: effective tool to improve knowledge, attitude and behavior
      regarding blood donation.
AB  - BACKGROUND: Annually, India meets only half of its blood requirement and half of
      it from unsafe blood donors. There is a need to increase blood donations from
      safe and voluntary blood donors. Recruitment and retainment of voluntary blood
      donors are key challenges for blood agencies. AIM: The aim of this study is to
      assess the impact of mass counseling in the creation of voluntary blood donor.
      SUBJECTS AND METHODS: Interventional study with intervention of mass counseling
      of relatives of patients admitted in the wards of Tertiary Care Hospital attached
      to medical college in Pune. It was carried out during 1(st) May 2010 to 31(st)
      May 2010. 110 relatives were randomly selected for the study. Mass counseling of
      cases regarding voluntary blood donation was carried out by trained persons. Pre
      counseling and post-counseling knowledge, attitude, and behavior (KAB) scores
      regarding blood donation were assessed using a pre-tested semi-structured
      questionnaire. RESULTS: Counseling improved knowledge, attitude and behavior
      score (KAB) regarding blood donation significantly. Pre-counseling and post
      counseling KAB scores difference was statistically significant (P < 0.001) and
      was not merely by chance. Counseling helped to improve behavior of cases
      regarding blood donation, too. CONCLUSION: Continuous counseling sessions for
      blood donation may serve the purpose for institutes dealing with a large number
      of people every-day. Establishment of mobile counseling units by blood banks may
      help to create a voluntary blood donor. Changes in motivation and the development
      of self-identity as a blood donor are needed to retain voluntary blood donors.
      Incentive's offered for voluntary blood donation card should be strengthened.

PMID- 24669339
TI  - Risk Factors for Acute Respiratory Tract Infections in Under-five Children in
      Enugu Southeast Nigeria.
AB  - BACKGROUND: Acute respiratory tract infections (ARIs) constitute the major causes
      of mortality and morbidity among under-five children of the developing world. The
      prevalence of ARIs is determined individually or collectively by a number of
      factors which may be prevalent in our environment. AIM: The present study is
      aimed to determine the risk factors that affect the prevalence of ARIs in under
      five children in Enugu. SUBJECTS AND METHODS: A cross-sectional study of 436
      under-five children diagnosed with ARI was carried out in three hospitals in
      Enugu. Participants were consecutively enrolled after being diagnosed as a case
      of ARI. Structured pro foma was used to collect sociodemographic characteristics,
      anthropometric data and risk profile. Data were analyzed using Epi info version
      6.0 and significant probability value was 5%. RESULTS: A total of 436 patients
      were enrolled for the study 224 males and 212 females M: F 1.06:1. The mean age
      of the population was 18.75(13.38) months and there were 31.6%(138/436) cases of
      pneumonia 6.9%(30/436) cases of bronchiolitis and 61.5%(268/436) cases of acute
      upper respiratory tract infections. Children less than 20 months accounted for
      60.9% (84/138 cases) of pneumonia, 86.7% (26/30 cases) of bronchiolitis, and
      64.5% (173/268 cases) of acute upper respiratory tract infections. Pneumonia was
      noted in about 75.7% (56/74) of inadequately nourished children compared to 22.6%
      (82/362) in adequately nourished children. Other risk factors identified in the
      study include inadequate breast feeding, poor immunization statues, attendance to
      daycare centers, large family size, poor parental educational statues, parental
      smoking, living in the urban area and use of biofuels. CONCLUSION: ARIs are
      affected by socio-demographic and socio-cultural risk factors, which can be
      modified with simple strategies. It is recommended that control program for ARIs
      should be multifaceted with a strong political will.

PMID- 24669340
TI  - Biofilms on indwelling urologic devices: microbes and antimicrobial management
      prospect.
AB  - BACKGROUND: Biofilms (BFs) are a potential source of highly resistant infections,
      frequently formed on devicesand pose problems for management. AIM: This study was
      to develop rational approach for prevention of indwelling urologic device
      associated biofilm colonization. SUBJECTS AND METHODS: From randomly selected
      patients visiting Department of Urology of a tertiary hospital in India 150 uro
      catheters and 31 used ureteric stents, in-situ for > 30, were collected
      aseptically. The organisms were isolated and identified from washed devices
      dipped in broth. Evidence of bacteriuria in each case was checked by semi
      quantitative method of urine culture, on day 0 and 14 of device use. The BF
      statuses of the device-adhered organisms were confirmed by modified method of
      Christensen. The antibiotic susceptibility was determined by disc diffusion
      method. Data were analyzed using the Graphpad Prism version 5 statistical
      software. RESULTS: Both single and multi-species BFs were formed on catheters,
      whereas mono-bacterial BFs were exclusive on stents. Predominant organisms were
      Pseudomonas aeruginosa (30.67%,69/225,) followed by Staphylococcus aureus
      (15.11%, 34/225), Escherichia coli (13.78%, 31/225), Klebsiella pneumoniae (12%,
      27/225), Staphylococcus epidermidis (8.44%, 19/225). Of all strains, (89.33%,
      201/225) were found to be BF positive and their colonizations were early
      indicated by the presence of insignificant bacteriuria in follow-up urine
      samples. All BF isolates were resistant to at least three antibiotics.
      CONCLUSIONS: BF colonization was almost inevitable in prolonged used urinary
      devices and the most frequent organisms were Pseudomonas, Staphylococcus, and
      Escherichia spp. Their colonizations usually were indicated by insignificant
      bacteriuria from follow-up samples. Such BF dislodged organisms were multidrug
      resistant and could be a source of disseminated infection, yet were in-vitro
      preventable by many drugs.

PMID- 24669341
TI  - Learning from health care workers' opinions for improving quality of neonatal
      health care in kilimanjaro region, northeast Tanzania.
AB  - BACKGROUND: There is a higher neonatal mortality rate while the adherence to the
      existing guidelines is rarely studied in Tanzania. AIM: The aim of this study is
      to assess the performance of health workers for neonatal health-care. MATERIALS
      AND METHODS: Settings - Peripheral health facilities (regional referral, district
      hospitals and health centers) and a tertiary referral hospital of Kilimanjaro
      region, Tanzania. Fourteen hospital facilities within all seven districts of the
      Kilimanjaro region wer involved in this cross-sectional descriptive study. Data
      were collected for 5 months from 26(th) November, 2010 to 25(th) April, 2011. We
      analyzed our quantitative data by using STATA v10 (StataCorp, TX, USA) for
      statistical comparison using Chi-square test to test the difference between the
      categories and odds ratio (OR) for association between independent and dependent
      variables. RESULTS: Birth asphyxia was the most recalled health problem requiring
      critical care, reported by 27.5% (33/120) of health-care workers (HCWs) at
      peripheral hospitals and at 46.4% (13/28) in a tertiary referral centers.
      Majority of HCWs commented on their own performance 47.5% (67/140). In the
      periphery (40), first comment was on management and follow-up of neonatal cases
      47.5% (19/40), second on a need of skills 45% (18/40) and third on timely
      referrals 7.5% (18/40). Shortage of proper equipment was reported at 26.4%
      (37/140), shortage of staff was reported at 12.0% (17/140), lack of organization
      of care 11.4% (16/140) and poor hygiene at 2.9% (4/140). It was hard to judge the
      impact of training on the sufficiency of knowledge (OR: 2.1; 95% confidence
      interval: [0.9 - 4.8]; P = 0.08) although levels of knowledge for critical
      neonatal care were higher at the tertiary referral hospital (Pearson chi(2) [2] =
      53.8; P < 0.001). CONCLUSION: Performance of HCWs in early neonatal care is
      suboptimal and requires frequent systematic evaluation.

PMID- 24669342
TI  - Evaluation of complications of extracapsular cataract extraction performed by
      trainees.
AB  - BACKGROUND: Cataract extraction is the most common intraocular surgery taught to
      residents. AIM: This study aims to review the complications of trainee-performed
      extracapsular cataract extraction (ECCE) so as to identify the steps in which the
      trainee can benefit from closer supervision and practice. SUBJECTS AND METHODS:
      This was a descriptive retrospective study of complications in the initial 150
      ECCE with intraocular lens implant performed by two Ophthalmologists, from the
      University of Nigeria Teaching Hospital, Enugu, who visited a high volume
      training center. Both the intraoperative and early post-operative complications
      were studied. Data entry and analysis were performed descriptively using the
      Statiscal Package for the Social Sciences, SPSS version 15.0 (Chicago, IL, USA).
      RESULTS: The age range of the patients was 40-95 years. The intraoperative
      complications included capsular flaps 12/161 (7.5%), posterior capsule rent,
      10/161 (6.2%) and vitreous loss, 8/161 (5.0%). Corneal complications (striate
      keratopathy, superior corneal edema, generalized corneal edema and corneal folds)
      ranked highest in post-operative complications accounting for 34% (56/164).
      CONCLUSIONS: Performance of adequate and proper anterior capsulotomy, minimal
      handling of the cornea and avoidance of posterior capsular rent are some of the
      challenges of the trainee in mastering ECCE. Stepwise supervised training can
      help a trainee master these steps while keeping the complications at acceptably
      low levels.

PMID- 24669343
TI  - Vulnerability and knowledge of sexually transmitted infections among female
      traders of reproductive age in enugu, Nigeria.
AB  - BACKGROUND: Sexually transmitted infections (STIs) constitute major public health
      concern and enigma. A comprehensive knowledge of the modes of transmission is
      necessary to evolve an effective preventive strategy. AIM: The aim of the study
      is to assess the vulnerability, knowledge and prevention of STIs among female
      traders of reproductive age in Enugu, Southeast Nigeria. SUBJECTS AND METHODS:
      This was a cross-sectional descriptive study carried out on female traders aged
      15-49 years at Ogbete Main Market, Enugu, Southeast Nigeria. Data was analyzed
      using Epi-Info 2000 version 3.3.1 Centers for Disease Control and Prevention
      Atlanta USA) was used to analyze the data and results were presented in tabular
      form. RESULTS: A total of 200 female traders of reproductive age participated in
      the study. The mean (standard deviation) age was 26 (7.4) years. 16% (32/200)
      were adolescents. Knowledge of specific STIs was highest for human
      immunodeficiency virus/acquired immune deficiency syndrome 90% (130/200). Parents
      were poor sources of information as only 28.5% (57/200) respondents heard about
      STIs from their parents compared with 46% (92/200) from friends and peers. Risk
      factors identified were multiple sexual partners 75.5% (151/200), non-use of
      condoms 62% (124/200) and early debut 58% (116/200). Majority 67.5% (135/200)
      were aware that STIs could be treated by a visit to the doctor while 21.5%
      (43/200) preferred traditional/herbal healers. CONCLUSION: The inclusion of
      health education in schools' curricula to ensure that adolescents are adequately
      aware of STIs, their modes of transmission, prevention and treatment before
      embarking on any vocation out-of-school is advocated.

PMID- 24669344
TI  - Subcutaneous surprise.
AB  - Melioidosis is a zoonosis caused by the accidental pathogen Burkholderia
      pseudomallei, which is endemic in Southeast Asia and northern Australia. The
      mortality of melioidosis is 20-50% even with treatment. Suppurative lymphadenitis
      caused by melioidosis has been rarely encountered by clinicians practicing in
      endemic areas. In the majority of previously described patients, the infected
      lymph nodes were in the head and neck region, except for four patients who
      presented with unilateral, inguinal lymphadenitis. Hence, we report a case of
      unilateral suppurative inguinal lymphadenitis caused by B. pseudomallei in a 48
      year-old lady who presented with groin swelling of 2 months duration. 

PMID- 24669345
TI  - Live Birth Following a Term Pregnancy in a Non-communicating Rudimentary Horn of
      a Unicornuate Uterus.
AB  - A case report of a live birth following a term pregnancy located in a non
      communicating rudimentary horn of a unicornuate uterus in a rural hospital in
      Nigeria is presented. A 32-year-old primiparous woman registered for antenatal
      care at a rural missionary hospital at 28 weeks gestation. She had intermittent
      unexplained vaginal bleeding prior to booking and multiple ultrasound scans in
      different centers affirmed a viable intrauterine pregnancy. She had an elective
      cesarean section at 38 weeks gestational age on account of a persistent oblique
      breech presentation and "low lying placenta." Intra-operatively, the pregnancy
      was found in a non-communicating pouch continuous with the left fallopian tube
      and separate from the uterine cavity. A female baby weighing 2.2 kg with no gross
      deformity was delivered. Resection of the rudimentary horn and repair were done.
      The possibility of a uterine anomaly should be considered by clinicians and
      sonographers in unexplained intermittent early pregnancy bleeding. 

PMID- 24669346
TI  - Primary labial tuberculosis: a rare presentation.
AB  - Tuberculosis is one of the oldest scorches of mankind that has not left this
      world even today. The disease is more common in the developing countries. Oral
      tuberculosis has been considered in 0.1-5% of all tuberculous infections. Mostly,
      the oral tuberculous lesions are secondary to pulmonary tuberculosis, but rarely
      primary lesions may occur. Primary lesions occur due to direct inoculation of the
      microorganism into the oral mucosa and mainly seen in the young individuals.
      Tongue is the most common oral site involved. Of all the sites involved, labial
      involvement is extremely rare. This case report intends to throw light on one
      such unique case, where a young male patient presented with a primary tubercular
      lesion of the lip. The lesion resolved immediately after anti tubercular therapy.

PMID- 24669347
TI  - A Type-II First Branchial Cleft Anomaly Presenting as a Post-Auricular Salivary
      Fistula: A Rare Presentation.
AB  - First branchial cleft anomalies are rare with the average age of presentation as
      19 years. There is an average delay of 3.5 years between initial presentation and
      adequate treatment due to diagnostic dilemma. A very rare variant of first
      branchial cleft anomaly presenting as a post-auricular salivary fistula is
      reported. A 12-year-old girl presented with a history of intermittent watery
      discharge, more so at the time of meals from a right post-auricular opening for
      last 3 years. Computed tomography sialography revealed a fistulous tract
      connecting the sub segmental duct of the parotid gland extending along the pre
      tragus region in subcutaneous plane up to mastoid tip after passing inferior to
      external auditory canal. Superficial parotidectomy with identification of facial
      nerve branches was carried out for excision of the tract. Histopathology revealed
      sinus tract comprising of ectodermal components and acini of the parotid gland.
      We classified our case into work's type-2 based on anatomical location at an
      angle of mandible, its relationship to parotid gland and facial nerve and
      previous history of ear discharge. To the best of our knowledge, this is the
      first case of its type to be reported. 

PMID- 24669348
TI  - Systemic lupus erythematosus presenting as acute adrenal insufficiency: a rare
      clinical presentation.
AB  - Systemic lupus erythematosus is a complex autoimmune disease with multisystem
      involvement with varied presentation. Autoimmune adrenal disease, on the other
      hand, can be associated with other autoimmune diseases. Adrenal insufficiency as
      a presenting feature of Systemic lupus erythematosus is a rare occurrence. We
      hereby report a case of a 20 year-old female who presented to us in an acute
      hypoadrenal state and was found to have Systemic lupus erythematosus with renal
      involvement. Patient was successfully managed with steroids and improved
      clinically. 

PMID- 24669349
TI  - Hydroxycut-induced Liver Toxicity.
AB  - In the recent era, use of various nutritional supplements is highly encouraged
      amongst the people of United States. Weight loss supplements are major part of
      the nutritional supplements and their usage is unregulated in the US. Obesity is
      a major health concern in the US and Americans spend around $30 billion a year
      for weight loss supplements. At times, these supplements can be responsible for
      documented or undocumented adverse drug effects. The health consequences related
      to these supplements are often overlooked by the general public, even though FDA
      issues advisories regarding them. One common supplement used for weight loss was
      Hydroxycut (Iovate Health Sciences Research, Oakville, Ontario, Canada).
      Hydroxycut was recalled from the market after a FDA warning in May 2009 because
      of 23 reports of serious health problems ranging from jaundice and elevated liver
      enzymes to liver damage. 1 This case report adds evidence for Hydroxycut -
      induced hepatotoxicity. A 27 year old man with right upper quadrant pain and
      jaundice was found to have elevated liver enzymes and was taking Hydroxycut along
      with other supplements. Liver biopsy showed drug induced hepatotoxicity.
      Discontinuation of Hydroxycut dramatically improved liver functions and related
      symptoms. 

PMID- 24669350
TI  - Low cost technology for screening early cancerous lesions of oral cavity in rural
      settings.
AB  - BACKGROUND: Low cost technologies are needed in resource poor rural settings for
      detection of pre-cancer and cancer lesions of the oral cavity. AIM: The study was
      undertaken to investigate the feasibility of a low cost technology
      (Magnivisualizer) for the early detection any lesions of the oral cavity among
      tobacco users in a resource poor rural field setting. SUBJECTS AND METHODS: A
      total of 1329 tobacco users were motivated to come forward for oral examination
      in the camp organized for this purpose. Their oral cavities were screened with a
      torch and Magnivisualizer by a Dentist. RESULTS: With torch light, 104/1329
      (7.8%) lesions were identified, though only 62/104 (59.6%) positive lesions could
      be differentiated into various categories. However, through Magnivisualizer
      156/1329 (11.7%) lesions were detected and 153/156 (98.1%) positive lesions were
      differentiated into different categories. CONCLUSION: Magnivisualizer offers an
      alternative instrument for detecting most of the early cancerous and high-grade
      precancerous lesions and it can be used in the rural field settings.

PMID- 24669352
TI  - Sublingual Immunotherapy for Asthma: Affects T-Cells but Does not Impact Basophil
      Activation.
AB  - Objective: Allergen-specific immunotherapy (SIT) is the unique modifying
      treatment of atopic diseases. Dysregulation of T-cell apoptosis plays a crucial
      role in the in the development of asthma. Nevertheless, the effect of sublingual
      immunotherapy (SLIT) on T-cell apoptosis has not been elucidated. The aim of the
      study was to evaluate the influence of 1 year of SIT in atopic children on the
      frequency of Th1 and Th2 cells in peripheral blood, on T-cell apoptosis, and on
      the response of basophils to allergen challenge. Methods: Children suffering from
      bronchial asthma were treated with SLIT for 12 months (Staloral 300). Basophil
      activation was evaluated by measurement of CD203c antigen expression. Th1 and Th2
      cells frequencies and their associated frequencies of apoptosis by the expression
      of Bcl-2 were evaluated with flow cytometry. Results: Basophil activation showed
      no difference in response before and after therapy. The frequency of Th1 cells
      increased (p=0.01, n=19), whereas the frequency of Th2 cells remained stable.
      Additionally, a significant increase of Bcl-2 positive Th1 cells was found
      (p=0.0465, n=19). Conclusions: We conclude that the increase in frequency of Th1
      cells secondary to SLIT might be associated with increased resistance to
      apoptotic signals. The basophil activation is not useful in evaluation of patient
      desensitization.

PMID- 24669351
TI  - Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia.
AB  - Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is a
      significant contributor to perinatal morbidity and mortality. Premature birth
      disrupts pulmonary vascular growth and initiates a cascade of events that result
      in impaired gas exchange, abnormal vasoreactivity, and pulmonary vascular
      remodeling that may ultimately lead to pulmonary hypertension (PH). Even infants
      who appear to have mild BPD suffer from varying degrees of pulmonary vascular
      disease (PVD). Although recent studies have enhanced our understanding of the
      pathobiology of PVD and PH in BPD, much remains unknown with respect to how PH
      should be properly defined, as well as the most accurate methods for the
      diagnosis and treatment of PH in infants with BPD. This article will provide
      neonatologists and primary care providers, as well as pediatric cardiologists and
      pulmonologists, with a review of the pathophysiology of PH in preterm infants
      with BPD and a summary of current clinical recommendations for managing PH in
      this population.

PMID- 24669353
TI  - Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness
      Severity, but not Childhood Asthma.
AB  - It is unknown whether gastroesophageal reflux disease (GERD) during infancy
      affects infant bronchiolitis severity or childhood asthma inception. Four hundred
      thirty-two infants presenting with acute respiratory illness due to bronchiolitis
      or upper respiratory infection were studied. The primary exposure was the
      parental report of a previous GERD diagnosis. Outcomes included bronchiolitis
      severity at initial presentation and childhood asthma diagnosis at age 4. Infants
      with parentally reported GERD had a higher bronchiolitis severity score (range=0
      12, clinically significant difference=0.5), indicating more severe disease, than
      infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among
      those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This
      association persisted after adjusting for infant age, race, gender, and
      secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99,
      95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD
      during infancy was not associated with the parental report of asthma diagnosis at
      age 4. GERD during infancy may contribute to acute respiratory illness severity,
      but is not associated with asthma diagnosis at age 4. Future prospective studies
      are needed to confirm these findings.

PMID- 24669354
TI  - A Qualitative Study of Phase III Cancer Clinical Trial Enrollment Decision
      Making: Perspectives from Adolescents, Young Adults, Caregivers, and Providers.
AB  - Purpose: The mortality reduction rate for adolescents and young adults (AYAs)
      with cancer has not demonstrated the same rate of improvement as for children,
      due partly to insufficient phase III cancer clinical trial enrollment. This study
      describes three key components of phase III cancer clinical trial enrollment
      family decision-making patterns, factors that influence AYAs' involvement, and
      attitudes (perceived barriers and benefits) toward trial participation-and
      evaluated a measure of attitudes. Methods: Participants were AYAs (15-23 years
      old at study) diagnosed with cancer and offered a phase III cancer clinical trial
      within the past 3-21 months, their primary caregivers, and their healthcare
      providers. Interviews assessed: (a) phase III clinical trial decision-making
      experiences and (b) relevance of the Pediatric Research Participation
      Questionnaire (PRPQ) in the assessment of AYAs' attitudes toward enrollment on
      phase III cancer clinical trials. Results: Thirteen AYAs, 16 caregivers, and 11
      providers were interviewed. Four decision-making patterns were identified, with
      AYA abdicates to caregiver and caregiver-based and AYA-endorsed the most commonly
      described, but with variation across respondents. Distress and reduced health
      related quality of life limited AYAs' involvement in the enrollment decision,
      while developmental and emotional maturity facilitated involvement. Perceived
      barriers and benefits to enrollment were reported, and the PRPQ was deemed
      relevant with minor modifications. Conclusions: Findings suggest that AYAs may
      not be fully involved in phase III cancer clinical trial enrollment decision
      making, and caregivers and providers are challenged to overcome factors that
      limit their involvement. The PRPQ shows promise as a tool for systematically
      evaluating clinical trial attitudes.

PMID- 24669355
TI  - Attitudes Toward Cancer Clinical Trial Participation in Young Adults with a
      History of Cancer and a Healthy College Student Sample: A Preliminary
      Investigation.
AB  - Purpose: Adolescents and young adults (AYAs) aged 15-39 at diagnosis have very
      low cancer clinical trial accrual rates. To date, no studies have examined
      attitudes toward clinical trial participation in this age range to determine if
      certain individuals are less likely to enroll if offered participation. The
      current study assessed attitudes toward participation using the Cancer Treatment
      Subscale of the Attitudes toward Cancer Trials Scales. Methods: Data were
      collected from a sample of leukemia and lymphoma survivors (n=99) and a healthy
      college student sample (n=397). Following a principal components analysis, two
      subscales-Personal Barriers/Safety and Personal Benefits-were retained for
      analysis. Results: In the cancer survivor group, only 14 (13.3%) reported being
      offered participation in a cancer clinical trial, and only 8 of those 14 (7.6% of
      survivors) participated. Responses from leukemia and lymphoma survivors revealed
      no significant relationships between age, gender, race/ethnicity, clinical trial
      participation, insurance status, or social class with Personal Benefits or
      Personal Barriers/Safety. Healthy college females had more negative Personal
      Barriers/Safety attitudes compared to males after adjusting for race/ethnicity
      and social class (p=0.01), but no associations were present when examining
      Personal Benefits as an outcome. Conclusion: This preliminary investigation
      suggests that drivers of attitudes toward clinical trial participation in AYAs
      are not well understood and may impact cancer trial participation. Future work
      should focus on defining attitudes toward cancer clinical trials in the AYA
      population and developing interventions to increase awareness, knowledge, and
      positive attitudes toward participating in cancer research.

PMID- 24669356
TI  - Geographical Factors Affecting the Admission of Teenagers and Young Adults to Age
      Specialist Inpatient Cancer Care in England.
AB  - Purpose: Little is known about the factors that influence the place of inpatient
      care for teenage and young adult (TYA) cancer patients. Recent guidelines have
      recommended centralization of care for this group to a small number of
      specialized centers. This study aimed to investigate the influence of geography
      and travel times on the likelihood of admission to an age-specialist center in
      England during cancer treatment for patients aged 15-24 at the time of diagnosis.
      Methods: Data for 6788 patients aged 15-24, diagnosed between 2001 and 2006 and
      treated as an inpatient in England between 2001 and 2009, were obtained from the
      National Cancer Data Repository. Eight TYA age-specialist centers were identified
      in England during this time period; road travel times to these centers were
      calculated using ArcGIS Network Analyst. Factors thought to affect the likelihood
      of admission, such as diagnostic group, gender, and age at diagnosis were modeled
      using logistic regression. Results: Overall, 66.9% of patients never received
      inpatient treatment at a TYA age-specialist center during the course of their
      treatment. Increasing travel time significantly reduced the likelihood of
      admission to a TYA age-specialist center after adjustment for case mix factors.
      Conclusion: Many TYA patients received little or no inpatient treatment at a TYA
      age-specialist center during their treatment. The variation between diagnostic
      groups suggests that factors other than distance to the closest center are
      affecting the likelihood of admission and demonstrates the potential need to
      consider improvements to the structured referral practice for this unique group
      of patients.

PMID- 24669357
TI  - A Feasibility Study to Measure Physical Activity, Fatigue, Sleep-Wake
      Disturbances, and Depression in Young Adults During Chemotherapy.
AB  - Little is known about the physical activity (PA) of young adults (YAs) during
      cancer therapy. In this feasibility study, 14 YAs (20-34 years old) completed a
      six-minute walk test, recorded their steps per day for one week, and answered
      weekly self-reports about physical activity, fatigue, sleep-wake disturbances,
      and depression during one cycle of chemotherapy. Findings suggest YAs are willing
      to complete a PA study during chemotherapy and have variable sleep and activity
      schedules. Their symptoms varied in severity, with highest scores for fatigue.
      Studies to improve PA in YAs during chemotherapy are warranted to manage short-
      and long-term treatment effects.

PMID- 24669358
TI  - Comparison of Markers and Functional Attributes of Human Adipose-Derived Stem
      Cells and Dedifferentiated Adipocyte Cells from Subcutaneous Fat of an Obese
      Diabetic Donor.
AB  - Objective: Adipose tissue is a robust source of adipose-derived stem cells
      (ADSCs) that may be able to provide secreted factors that promote the ability of
      wounded tissue to heal. However, adipocytes also have the potential to
      dedifferentiate in culture to cells with stem cell-like properties that may
      improve their behavior and functionality for certain applications. Approach:
      ADSCs are adult mesenchymal stem cells that are cultured from the stromal
      vascular fraction of adipose tissue. However, adipocytes are capable of
      dedifferentiating into cells with stem cell properties. In this case study, we
      compare ADSC and dedifferentiated fat (DFAT) cells from the same patient and fat
      depot for mesenchymal cell markers, embryonic stem cell markers, ability to
      differentiate to adipocytes and osteoblasts, senescence and telomerase levels,
      and ability of conditioned media (CM) to stimulate migration of human dermal
      fibroblasts (HDFs). Innovation and Conclusions: ADSCs and DFAT cells displayed
      identical levels of CD90, CD44, CD105, and were CD34- and CD45-negative. They
      also expressed similar levels of Oct4, BMI1, KLF4, and SALL4. DFAT cells,
      however, showed higher efficiency in adipogenic and osteogenic capacity.
      Telomerase levels of DFAT cells were double those of ADSCs, and senescence
      declined in DFAT cells. CM from both cell types altered the migration of
      fibroblasts. Despite reports of ADSCs from a number of human depots, there have
      been no comparisons of the ability of dedifferentiated DFAT cells from the same
      donor and depot to differentiate or modulate migration of HDFs. Since ADSCs were
      from an obese diabetic donor, reprogramming of DFAT cells may help improve a
      patient's cells for regenerative medicine applications.

PMID- 24669361
TI  - Epidermal Differentiation in Barrier Maintenance and Wound Healing.
AB  - Significance: The epidermal barrier prevents water loss and serves as the body's
      first line of defense against toxins, chemicals, and infectious microbes.
      Disruption of the barrier, either through congenital disorders of barrier
      formation or through wounds, puts the individual at risk for dehydration,
      hypersensitivity, infection, and prolonged inflammation. Epidermal barrier
      disorders affect millions of patients in the United States, causing loss of
      productivity and diminished quality of life for patients and their families, and
      represent a burden to the health-care system and society. Recent Advances: The
      genetic basis of many congenital barrier disorders has been identified in recent
      years, and great advances have been made in the molecular mechanisms of the
      formation and homeostasis of epidermal barrier, as well as acute and chronic
      wound healing. Progress in stem cell (SC) biology, particularly in induced
      pluripotent stem cells (iPSCs) and allogeneic mesenchymal stem cells (MSCs), has
      opened new doors for cell-based therapy of chronic wounds. Critical Issues:
      Understanding of the molecular mechanisms of barrier homeostasis in health and
      disease, as well as contributions of iPSCs and allogeneic MSCs to wound healing,
      will lead to the identification of novel targets for developing therapeutics for
      congenital barrier and wound healing disorders. Future Directions: Future studies
      should focus on better understanding of molecular mechanisms leading to disrupted
      homeostasis of epidermal barrier to identify potential therapeutic targets to
      combat its associated diseases.

PMID- 24669359
TI  - Integrin Regulation of Epidermal Functions in Wounds.
AB  - Significance: Integrins are bidirectional signaling receptors for extracellular
      matrix that regulate both inside-out signaling that controls keratinocyte
      mediated changes to the wound microenvironment and outside-in signaling that
      controls keratinocyte responses to microenvironmental changes. As such, integrins
      represent attractive therapeutic targets for treatment of chronic wounds or
      general promotion of wound healing. Advances in wound management are particularly
      important as the elderly and diabetic populations within the United States
      continue to grow. Recent Advances: Although integrins are best known for
      mediating cell adhesion and migration, integrins in wound epidermis also control
      cell survival, proliferation, matrix remodeling, and paracrine crosstalk to other
      cellular compartments of the wound. Importantly, the concept of targeting
      integrins in the clinic has been established for treatment of certain cancers and
      other diseases, laying the groundwork for similar exploitation of integrins as
      targets to treat chronic wounds. Critical Issues: Despite their attractiveness as
      therapeutic targets, integrins have complex roles in wound healing that are
      impacted by both their own expression and a highly dynamic wound microenvironment
      that determines ligand availability. Therefore, identifying relevant integrin
      ligands in the wound and understanding both distinct and overlapping functions
      that different integrins play in the epidermis will be critical to determine
      their precise roles in wound healing. Future Directions: Future research should
      focus on gaining a thorough understanding of the highly coordinated functions of
      different integrins in wound epidermis, and on determining which of these
      functions go awry in pathological wounds. This focus should facilitate
      development of integrin-targeting therapeutics for treating chronic wounds.

PMID- 24669360
TI  - Focal Contact and Hemidesmosomal Proteins in Keratinocyte Migration and Wound
      Repair.
AB  - Significance: During wound healing of the skin, keratinocytes should move over
      while still adhering to their underlying matrix. Thus, mechanistic insights into
      the wound-healing process require an understanding of the forms and functions of
      keratinocyte matrix adhesions, specifically focal contacts and hemidesmosomes,
      and their components. Recent Advances: Although the structure and composition of
      focal contacts and hemidesmosomes are relatively well defined, the functions of
      their components are only now being delineated using mouse genetic models and
      knockdown approaches in cell culture systems. Remarkably, both focal contact and
      hemidesmosomal proteins appear involved in determining the speed and directional
      migration of epidermal cells by modulating several signal transduction pathways.
      Critical Issues: Although many publications are centered on focal contacts, their
      existence in tissues such as the skin is controversial. Nonetheless, focal
      contact proteins are central to mechanisms that regulate skin cell motility.
      Conversely, hemidesmosomes have been identified in intact skin but whether
      hemidesmosomal components play a positive regulatory function in keratinocyte
      motility remains debated in the field. Future Directions: Defective wound healing
      is a developing problem in the aged, hospitalized and diabetic populations.
      Hence, deriving new insights into the molecular roles of matrix adhesion proteins
      in wound healing is a prerequisite to the development of novel therapeutics to
      enhance tissue repair and regeneration.

PMID- 24669362
TI  - SERPINE1: A Molecular Switch in the Proliferation-Migration Dichotomy in Wound
      "Activated" Keratinocytes.
AB  - Significance: A highly interactive serine protease/plasmin/matrix
      metalloproteinase axis regulates stromal remodeling in the wound
      microenvironment. Current findings highlight the importance of stringent controls
      on protease expression and their topographic activities in cell proliferation,
      migration, and tissue homeostasis. Targeting elements in this cascading network
      may lead to novel therapeutic approaches for fibrotic diseases and chronic
      wounds. Recent Advances: Matrix-active proteases and their inhibitors orchestrate
      wound site tissue remodeling, cell migration, and proliferation. Indeed, the
      serine proteases urokinase plasminogen activator and tissue-type plasminogen
      activator (uPA/tPA) and their major phsyiological inhibitor, plasminogen
      activator inhibitor-1 (PAI-1; serine protease inhibitor clade E member 1
      [SERPINE1]), are upregulated in several cell types during injury repair.
      Coordinate expression of proteolytic enzymes and their inhibitors in the wound
      bed provides a mechanism for fine control of focal proteolysis to facilitate
      matrix restructuring and cell motility in complex environments. Critical Issues:
      Cosmetic and tissue functional consequences of wound repair anomalies affect the
      quality of life of millions of patients in the United States alone. The
      development of novel therapeutics to manage individuals most affected by healing
      anomalies will likely derive from the identification of critical, translationally
      accessible, control elements in the wound site microenvironment. Future
      Directions: Activation of the PAI-1 gene early after wounding, its prominence in
      the repair transcriptome and varied functions suggest a key role in the global
      cutaneous injury response program. Targeting PAI-1 gene expression and/or PAI-1
      function with molecular genetic constructs, neutralizing antibodies or small
      molecule inhibitors may provide a novel, therapeutically relevant approach, to
      manage the pathophysiology of wound healing disorders associated with deficient
      or excessive PAI-1 levels.

PMID- 24669363
TI  - Impact of donor-specific antibodies on the outcomes of kidney graft:
      Pathophysiology, clinical, therapy.
AB  - Allo-antibodies, particularly when donor specific, are one of the most important
      factors that cause both early and late graft dysfunction. The authors review the
      current state of the art concerning this important issue in renal
      transplantation. Many antibodies have been recognized as mediators of renal
      injury. In particular donor-specific-Human Leukocyte Antigens antibodies appear
      to play a major role. New techniques, such as solid phase techniques and Luminex,
      have revealed these antibodies from patient sera. Other new techniques have
      uncovered alloantibodies and signs of complement activation in renal biopsy
      specimens. It has been acknowledged that the old concept of chronic renal injury
      caused by calcineurine inhibitors toxicity should be replaced in many cases by
      alloantibodies acting against the graft. In addition, the number of patients on
      waiting lists with preformed anti-human leukocyte antigens (HLA) antibodies is
      increasing, primarily from patients with a history of renal transplant failure
      already been sensitized. We should distinguish early and late acute antibody
      mediated rejection from chronic antibody-mediated rejection. The latter often
      manifets late during the course of the post-transplant period and may be
      difficult to recognize if specific techniques are not applied. Different
      therapeutic strategies are used to control antibody-induced damage. These
      strategies may be applied prior to transplantation or, in the case of acute
      antibody-mediated rejection, after transplantation. Many new drugs are appearing
      at the horizon; however, these drugs are far from the clinic because they are in
      phase I-II of clinical trials. Thus the pipeline for the near future appears
      almost empty. 

PMID- 24669364
TI  - ABO incompatible renal transplants: Good or bad?
AB  - ABO incompatible kidney transplantation (ABOi-KT) was previously considered to be
      an absolute contraindication for patients with end-stage kidney disease (ESKD)
      due to hyperacute rejection related to blood type barrier. Since the first
      successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all
      over the world. ABOi-KT has led to an expanded donor pool and reduced the number
      of patients with ESKD awaiting deceased kidney transplantation (KT). Intensified
      immunosuppression and immunological understanding has helped to shape current
      desensitization protocols. Consequently, in recent years, ABOi-KT outcome is
      comparable to ABO compatible KT (ABOc-KT). However, many questions still remain
      unanswered. In ABOi-KT, there is an additional residual immunological risk that
      may lead to allograft damage, despite using current diverse but usually
      intensified immunosuppressive protocols at the expense of increasing risk of
      infection and possibly malignancy. Notably, in ABOi-KT, desensitization and
      antibody reduction therapies have increased the cost of KT. Reassuringly, there
      has been an evolution in ABOi-KT leading to a simplification of protocols over
      the last decade. This review provides an overview of the history, outcome,
      protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT
      should be recommended as a therapeutic option of KT in the future. 

PMID- 24669366
TI  - Shortening the etching time for etch-and-rinse adhesives increases the bond
      stability to simulated caries-affected primary dentin.
AB  - PURPOSE: To evaluate the influence of shortening the etching time on the bond
      degradation of one etch-and-rinse and one two-step self-etching adhesive system
      to sound (SD) and caries-affected (CAD) dentin of deciduous teeth. MATERIALS AND
      METHODS: Flat dentin surfaces from 48 deciduous molars were assigned to 8 groups
      according to substrate (SD and CAD, pH cycling for 14 days), adhesive system
      (Adper Single Bond 2 [SB] and Clearfil SE Bond [CSEB]), and etching time
      (recommended by manufacturers and half the recommended etching time). Composite
      buildups were constructed and sectioned to obtain bonded sticks (0.8 mm2) to be
      subjected to microtensile testing immediately or after 12 months of water aging.
      Two sticks from each tooth at each time were immersed in silver nitrate solution
      to qualitatively assess nanoleakage. The microtensile bond strength (MUTBS)
      values of each adhesive were submitted to three-way repeated measures ANOVA and
      Tukey's post-hoc tests (alpha = 0.05). RESULTS: The etching time influenced the
      bond strength only for SB. The highest MUTBS values and lowest silver nitrate
      uptake were observed when half the recommended acid-etching time was used,
      regardless of substrate. Water storage for 12 months reduced bond strengths,
      except to CSEB bonded to SD. The MUTBS values obtained for CAD were lower than
      for SD, irrespective of adhesive system. Nanoleakage was more pronounced in CAD.
      CONCLUSION: The effect of shortening the etching time is material dependent and
      results in better bond stability for sound and caries-affected dentin of
      deciduous teeth when an etch-and-rinse adhesive system is employed.

PMID- 24669365
TI  - Immune monitoring post liver transplant.
AB  - Many of the causes of short and late morbidity following liver transplantation
      are associated with immunosuppression or immunosuppressive medications. Current
      care often involves close monitoring of liver biochemistry as well as therapeutic
      drug levels. However, the postoperative course following liver transplantation
      can often be associated with significant complications including infection and
      rejection, suggesting an inadequacy in current immune function monitoring. Many
      assays have been tested in the research setting to identify possible biomarkers
      that may be used to predict clinical events such as acute cellular rejection, and
      therefore allow modification of a patient's immunosuppressive regimen prior to a
      clinical event. However, these generally require significant laboratory
      processing and have had difficulty becoming established in common clinical use
      outside the research setting. One assay, Cylex ImmuKnow has been food and drug
      administration approved but has had variable results. In this review we discuss
      the assays that have been used to assess monitoring of immune function after
      liver transplantation and consider possible future directions. 

PMID- 24669367
TI  - Does the method of caries induction influence the bond strength to dentin of
      primary teeth?
AB  - PURPOSE: To evaluate the effect of chemical and microbiological methods of caries
      induction on microtensile bond strength (MUTBS) of current adhesive systems to
      primary dentin. MATERIALS AND METHODS: Flat dentin surfaces from 36 primary
      molars were assigned to 3 groups according to the method of inducing caries
      affected dentin: (1) control (sound dentin); (2) pH cycling; and (3)
      microbiological. In both methods, teeth were submitted to caries induction for 14
      days, and the sound dentin was stored in distilled water for the same period.
      Specimens were then randomly reassigned according to adhesive system: a two-step
      etch-and-rinse adhesive (Adper Single Bond 2) or a two-step self-etching system
      (Clearfil SE Bond). Composite buildups were constructed and the teeth were
      sectioned to obtain bonded sticks (0.8 mm2) to be tested for microtensile bond
      strength. The MUTBS means were analyzed by two-way ANOVA and Tukey's tests (alpha
      = 0.05). Failure mode was evaluated using a stereomicroscope (400X). RESULTS:
      Both methods of caries induction resulted in lower MUTBS values (with no
      significant difference between them) than those obtained for sound dentin.
      Adhesive systems showed similar bond strength values. The percentage of premature
      failure was higher in the microbiological group, regardless of adhesive system.
      CONCLUSION: Microbiological and pH-cycling methods are both suitable for
      simulating caries-affected dentin for bonding evaluations in primary teeth.

PMID- 24669368
TI  - Streptococcus mutans biofilm formation and release of fluoride from experimental
      resin-based composites depending on surface treatment and S-PRG filler particle
      fraction.
AB  - PURPOSE: To evaluate fluoride release and biofilm formation on resin-based
      composites (RBCs) including surface pre-reacted glass ionomer (S-PRG) filler
      particles. MATERIALS AND METHODS: Specimens were prepared from experimental RBCs
      including different fractions of S-PRG fillers (0/10/30/50/70% w/v). RBCs were
      light cured against mylar strips (MYL), and 50% of the specimens were
      additionally polished to a high gloss (POL). Surface roughness (SR), surface free
      energy (SFE) and fluoride release were determined. Streptococcus mutans biofilm
      formation (SMBF) was simulated for 48 h and 120 h; adherent viable biomass was
      assessed using an MTT-based assay. RESULTS: The highest SR was identified for POL
      specimens manufactured from the RBC with a filler fraction of 70%. For all
      specimens and surface treatments, polishing caused an increase in surface free
      energy. For both MYL and POL specimens, increasing the filler fraction coincided
      with an increased release of fluoride; a higher release of fluoride was
      identified for POL specimens with filler fractions of 50% and 70% in comparison
      to their MYL counterparts. Release of fluoride was lower after 120 h than after
      48 h. No differences in SMBF were identified between MYL and POL specimens with
      identical filler fractions after 48 h of biofilm formation; with increasing
      filler fractions, a tendency towards decreasing SMBF was observed. After 120 h,
      less SMBF was identified for POL specimens with filler fractions of 30%, 50% and
      70% in comparison to corresponding MYL specimens. CONCLUSION: The inclusion of S
      PRG fillers and an effective surface treatment may reduce biofilm formation on
      RBCs.

PMID- 24669369
TI  - Microtensile bond strength between indirect composite resin inlays and dentin:
      effect of cementation strategy and mechanical aging.
AB  - PURPOSE: To evaluate the microtensile bond strength of indirect resin composite
      inlays to dentin using two cementation strategies, before and after mechanical
      aging. MATERIALS AND METHODS: Standardized inlay cavities (bucco-lingual width: 3
      mm; depth: 4 mm) were prepared in 32 human premolars. The teeth were embedded in
      self-curing acrylic resin up to 3 mm from the cementoenamel junction, impressions
      were made using a polyvinyl siloxane material, master dies were obtained using
      type 4 stone, and inlay composite resin restorations were fabricated (Sinfony, 3M
      ESPE). The teeth were randomly allocated into 4 groups according to the
      cementation strategy (conventional [C] and simplified [S]) and aging (mechanical
      cycling [MC] and not aged): C[G1]: Adper SingleBond + RelyX ARC without aging;
      CMC[G2]: conventional cementation + mechanical cycling (106 cycles, 88 N, 4 Hz,
      +/- 37 degrees C); S[G3]: self-adhesive resin cement (RelyX U-100) without aging;
      SMC[G4] self-adhesive cementation + mechanical cycling. Intaglio surfaces of
      composite inlays were treated by tribochemical silica coating in G1 and G2, while
      G3 and G4 received no surface treatment. Non-aged specimens were stored in a
      moist environment at ca 37 degrees C for the same period as MC (3 days). Non
      trimmed beam specimens (bonding area = 1 mm2) were produced by serial cutting,
      and microtensile testing was performed (0.5 mm/min). RESULTS: Two-way ANOVA
      showed that the microtensile bond strength was affected only by cementation
      strategy (p < 0.0001). Tukey's test showed that groups G1 (35.1 +/- 9.1) and G2
      (32.7 +/- 10.7) presented significantly higher bond strength values than G3 (8.7
      +/- 6.3) and G4 (5.2 +/- 4.6). CONCLUSION: The use of a conventional adhesive
      technique and tribochemical silica coating resulted in higher MUTBS than the one
      step simplified cementation, even after mechanical cycling.

PMID- 24669370
TI  - Rhodamine based dual probes for selective detection of mercury and fluoride ions
      in water using two mutually independent sensing pathways.
AB  - New rhodamine based molecules have been designed as dual probes for the ppb-level
      selective detection of Hg(2+) and F(-) ions in aqueous medium at physiological pH
      7.4. The probes have been designed in such a way to utilize both the properties
      of the metal ion induced 'turn-on' detection mechanism of the spirolactam ring
      opening of the rhodamine moiety and the reaction based cleavage of the O-silyl
      bond in presence of the fluoride ion. The probes have been synthesized
      conveniently by coupling rhodamine hydrazone with O-silyl protected mono- and di
      hydroxybenzaldehydes. Both the probes showed a 'turn-on' detection of the
      fluoride ion due to the cleavage of the O-silyl bond upon treatment with the
      added F(-) ion. However, the probes showed selective 'turn-on' detection of
      Hg(2+) ion by opening of the spirolactam ring. The two detection mechanisms
      worked in isolation and hence the corresponding spectral responses appeared
      completely independent of each other. The presence of Hg(2+) in solution induced
      generation of an intense pink color with bright green fluorescence emission. In
      contrast a deep yellow color with yellow fluorescence was observed upon addition
      of the fluoride ion to the probe solution. Two different mechanisms of
      interactions have been proposed on the basis of (1)H-NMR, IR and mass
      spectrometric studies. Thus, using a single probe the selective sensing of two
      different ions could be achieved in aqueous medium well below their permitted
      limit of detection. 

PMID- 24669372
TI  - Exotropia-hypotropia complex in high myopia.
AB  - PURPOSE: To highlight the association of exotropia-hypotropia complex in cases of
      high myopia and its surgical outcome. METHODS: A retrospective study of 15
      consecutive patients, diagnosed as having high myopia and exotropia-hypotropia,
      observed between January 2002 and May 2012 was performed. The main outcome
      measures were clinical presentation, orbital imaging features, and the surgical
      outcome of cases. RESULTS: Of the 15 patients, 9 were female. The median age was
      23.5 years (range: 10 to 35 years). Thirteen cases had unilateral high myopia in
      the deviated eye. The mean axial length of the deviated eye was 29.43 +/- 1.51
      mm. Eight patients (53%) had a history of progressive eye deviation in adulthood.
      All patients had amblyopia of the deviating eye. The mean preoperative exotropia
      was 37.2 +/- 8.72 prism diopters (PD) (range: 18 to 50 PD). The mean preoperative
      hypotropia was 12.73 +/- 5.58 PD (range: 5 to 20 PD). An elevation deficit was
      noted in 6 patients (40%). On orbital imaging, high myopic eyes with deviation
      did not show significant displacement of rectus muscles in comparison to fellow
      eyes (P > .05, all rectus muscles). Eight cases (53%) were surgically managed
      with a median follow-up of 7 months. Intraoperatively, one case was found to have
      misplaced muscle insertion. Successful alignment was achieved by surgery on
      either horizontal rectus muscles alone (37%), or in combination with vertical
      muscles (62%). CONCLUSIONS: Exotropia-hypotropia complex can occur in association
      with high myopia. No specific etiologic factors, clinical or radiological, were
      identified in this study. Successful alignment may be achieved in these cases
      using tailor-made strabismus procedures.

PMID- 24669373
TI  - Combination treatment of pediatric coats' disease: a bicenter study in Taiwan.
AB  - PURPOSE: To present the clinical outcome of different combination treatment
      modalities in pediatric Coats' disease in two Taiwan medical centers. METHODS: A
      retrospective review of clinical records was done of pediatric patients with
      Coats' disease treated at National Taiwan University Hospital and Changhua
      Christian Hospital. Data regarding the age at the time of diagnosis, initial
      presentation, methods of treatment, visual and anatomic results, and
      complications were recorded. Changes in vision and retinal status with the
      different methods of treatment were specifically evaluated. RESULTS: From 2005
      through 2011, 10 eyes of 9 patients were treated under the diagnosis of Coats'
      disease. The clinical manifestations varied from localized vascular abnormalities
      with subretinal fluid and hard exudates to extensive detachment with massive
      exudates and retinal hemorrhage. The main treatment modalities include argon
      laser photocoagulation, micropulse laser, and cryotherapy. The adjunctive
      therapies included intravitreal triamcinolone, bevacizumab, and ranibizumab. The
      mean follow-up was 40.50 +/- 20.52 months (range: 14 to 72 months). Best
      corrected visual acuity at last follow-up was light perception to 1.0 (20/20
      Snellen). Anatomic improvement was achieved in 9 eyes (90%). Visual improvement
      was noted in 7 eyes (70%), visual stabilization in 2 eyes (20%), and visual
      deterioration in 1 eye (10%). Vitreous fibrosis evolving into tractional retinal
      detachment occurred in 1 patient receiving cryotherapy combined with intravitreal
      bevacizumab injections. No enucleation was ultimately necessary. CONCLUSIONS:
      Pediatric Coats' disease varies greatly in severity. Carefully selected treatment
      modalities can improve most eyes with different conditions. Intravitreal anti
      vascular endothelial growth factor agents may act as useful adjuncts to improve
      anatomic and functional outcome. Cryotherapy combined with the intravitreal
      bevacizumab injection in severe cases of exudative retinal detachment may carry
      the risk of vitreoretinal traction and tractional retinal detachment.

PMID- 24669374
TI  - Anterior visual pathways in amblyopia: quantitative assessment with diffusion
      tensor imaging.
AB  - PURPOSE: To detect the abnormalities of the anterior visual pathways in children
      with amblyopia with diffusion tensor imaging. METHODS: Ten children with
      unilateral amblyopia, 5 children with bilateral amblyopia, and 10 control
      children were treated using diffusion tensor imaging scanning in this
      institutional practice. Fractional anisotropy and mean diffusivity values were
      analyzed using diffusion tensor imaging in the prechiasmatic and chiasmatic
      regions. Fractional anisotropy and mean diffusivity values of the amblyopic
      groups were compared with the values of the control group using the Kruskal
      Wallis test. The Mann-Whitney U test was used to evaluate pairwise differences
      between groups. RESULTS: When compared with the control group, prechiasmatic
      fractional anisotropy values were significantly decreased in both affected and
      sound fellow eyes in the unilateral amblyopic group (P = .019 and .013), but not
      in the bilateral amblyopic group (P = .221). Mean diffusivity values were
      significantly greater in the sound fellow eye in the unilateral amblyopic group
      in the prechiasmatic region (P = .001 and .049). CONCLUSION: Diffusion tensor
      imaging showed a significant decrease in fractional anisotropy and an increase in
      mean diffusivity values in the unilateral amblyopic group in both affected and
      sound fellow eyes. These findings may reflect axonal underdevelopment in anterior
      pathways, particularly in the unilateral amblyopic group.

PMID- 24669375
TI  - Indications for and outcomes of deep anterior lamellar keratoplasty in
      mucopolysaccharidoses.
AB  - PURPOSE: To describe the outcome of deep anterior lamellar keratoplasty (DALK)
      for visually significant corneal clouding in patients with mucopolysaccharidoses
      (MPS). METHODS: A retrospective consecutive case series of patients with MPS and
      corneal clouding were analyzed at a tertiary eye hospital. A review of the
      English literature regarding MPS and DALK was performed. The main outcomes
      measures of the study were intraoperative surgical complications, change in
      visual acuity, and postoperative DALK-related complications. RESULTS: Four eyes
      from 2 patients with MPS I (Hurler's syndrome and Hurler-Scheie syndrome) and a
      history of DALK met inclusion criteria for the case series. Using the "big
      bubble" technique, DALK was performed successfully in all eyes. Completed
      Descemet's membrane baring was achieved in 3 or 4 eyes and a pre-Descemet's
      membrane dissection in 1 eye. The mean age at the time of DALK was 17.3 years
      (range: 15.4 to 19.5 years). Mean follow-up time after DALK was 16.7 months
      (range: 6 to 31 months). Mean visual acuity before DALK was 20/80 (0.59 +/- 0.12
      logMAR). Mean visual acuity at the last visit for all 4 eyes was 20/50 (0.41 +/-
      0.17 logMAR). Visual acuity improved in all eyes. Recurrence of MPS corneal
      clouding was not noted in any of the corneal grafts. CONCLUSIONS: DALK is a
      beneficial and preferable intervention in appropriate patients with significant
      corneal clouding due to MPS I. Improvement in vision can be obtained with stable,
      clear corneal grafts, although other ophthalmic manifestations may limit vision.

PMID- 24669376
TI  - Ocular problems in low-income and minority children.
AB  - PURPOSE: To report the prevalence rates of screen failures for uncorrected
      refractive error, abnormal or excessive levels of hyperopia, problems in
      binocular vision, and deficiency of near point acuity as related to age and
      ethnicity in children. METHODS: Vision screening tests were administered to 9,743
      African-American, Hispanic, and white children aged 6 to 11 years in the Kansas
      City (United States) metropolitan area. Screening was performed by health
      professions students using HOTV charts for refractive errors, hyperopia, and near
      point acuity and a Random Dot E test for binocular vision. Children were screened
      in their elementary schools, located in primarily poor, urban neighborhoods. The
      main outcome measure was pass/fail outcomes from screenings, with confirmation of
      screen fails by licensed health care professionals. RESULTS: For African-American
      children, 14.1% failed one or more vision screening tests. The corresponding
      screen failure rates for Hispanic and white children were 14.2% and 11.0%,
      respectively. There were significant differences in screening failure rates as a
      function of age and ethnicity, depending on the specific test. The highest rates
      of screen failures occurred in the 9 to 11 year old age range. CONCLUSIONS:
      Vision screening failures were frequently associated with age and ethnicity.
      Screening performed by health professions students can successfully identify
      potential visual problems at rates similar to those reported in studies using
      more complex, sophisticated testing performed by specially trained individuals.

PMID- 24669377
TI  - Preface.Pathogenesis of Mycobacterium tuberculosis and its interaction with the
      host organism.

PMID- 24669378
TI  - The clinical and economic consequences of obesity.
AB  - Obesity and its many serious comorbidities exert a heavy toll in both human and
      economic terms. More than one-third of adults in the United States are obese and,
      therefore, subject to elevated rates of diabetes, hypertension, dyslipidemia, and
      other cardiovascular disease risk factors. The negative effect on the quality of
      life (QoL) of these individuals is enormous. Among the severely obese, QoL scores
      are comparable to QoL scores associated with diabetes and laryngeal cancer. The
      medical costs of obesity-related illnesses in the United States have been
      estimated at $209.7 billion annually (in 2008 dollars). For example, with regard
      to impact on pharmaceutical costs, obesity is associated with a more than 13-fold
      increase in the cost of antidiabetic medications. The cost of absenteeism to
      employers has been estimated to exceed $4.3 billion annually. Successful and cost
      effective short-term treatments for obesity are available, and have been shown to
      reduce cardiovascular risk factors. Intensive lifestyle intervention with the
      goal of losing 7% of baseline body weight, for example, resulted in a 58%
      reduction in the risk of diabetes in patients with prediabetes. In clinical
      trials, improvements in other cardiovascular risk factors, such as elevated
      triglycerides and high blood pressure, have also been seen with a modest weight
      loss of 5% to 10% of baseline body weight. As obesity becomes an ever greater
      public health problem, additional interventions with long-term efficacy are
      needed to reduce body weight and maintain weight loss.

PMID- 24669379
TI  - Early interaction between infants and their parents predicts social competence at
      the age of four.
AB  - AIM: To investigate the impact that the interaction between first-born children
      and their parents, from the age of 3 months, has on peer and social competence
      when the children are 4 years of age. METHODS: Fifteen families were videotaped
      in Lausanne Trilogue Play situations (child-mother-father interactions), when the
      children were three, nine, 18 and 48 months of age. The findings were then
      related to peer and social competence assessments carried out by preschool
      teachers when the children were four. RESULTS: There was a correlation between
      the parents' responsiveness and the child's capacity to initiate (make
      contributions to) turn-taking sequences in the family triad early in life. This,
      in turn, was associated with the child's later peer and social competence. At the
      age of 3 months, the child's contributions to the triadic interaction were
      interpreted by the parents as intentional communication. According to the
      preschool teachers' assessments, children who initiated turn-taking sequences at
      9 months of age had better peer competence (p = 0.008) and social competence (p =
      0.028) at 48 months. CONCLUSION: The results highlight the opportunities that
      parents have to stimulate their child's later social competence. They also show
      that a Lausanne Trilogue Play situation can be used to identify competent
      children and children/families with communication deficits.

PMID- 24669380
TI  - Generics: just who can be trusted?

PMID- 24669381
TI  - Apixaban and atrial fibrillation: no clear advantage.
AB  - For the prevention of thromboembolic events in patients with atrial fibrillation
      and a high thrombotic risk, the standard treatment is warfarin, an anticoagulant.
      Dabigatran, a thrombin inhibitor, is the alternative when warfarin fails to
      maintain the INR within the therapeutic range. Patients with a moderate
      thrombotic risk may receive either warfarin or low-dose aspirin. Apixaban, a
      factor Xa inhibitor anticoagulant, has been authorised in the European Union for
      use in patients with non-valvular atrial fibrillation and a moderate or high risk
      of thrombosis. In a double-blind, randomised non-inferiority trial versus
      warfarin in 18 201 patients, the incidence of stroke or systemic embolism was
      lower in the apixaban group (average 1.3 versus 1.6 events per 100 patient-years;
      p = 0.01). This difference was mainly due to a lower incidence of haemorrhagic
      stroke and did not result in a clear decline in mortality. In addition, these
      results are undermined by multiple methodological flaws. Clinical evaluation
      included no trials comparing apixaban with dabigatran; any indirect comparison
      would be risky given the poor quality of the clinical assessment of both drugs in
      atrial fibrillation. A double-blind, randomised trial including 5598 patients
      compared apixaban with aspirin but provided little information on these options
      in patients with a moderate risk of thrombosis, as most patients were at high
      risk. In clinical trials, major bleeding events were less frequent with apixaban
      than with warfarin (average 2.1 versus 3.1 events per 100 patient-years), but
      they were more frequent with apixaban than with aspirin (1.4 versus 0.9 events
      per 100 patient-years). In 2013, there is no way of monitoring the anticoagulant
      activity of apixaban in routine clinical practice, and there is no antidote in
      case of overdose; the same is true for dabigatran. Apixaban is a substrate for
      various cytochrome P450 isoenzymes and for P-glycoprotein, creating a risk of
      multiple drug-drug interactions. In addition, the anticoagulant action of
      apixaban is increased by renal failure, meaning that renal function must be
      regularly monitored. In practice, the antithrombotic treatment of choice for
      patients with atrial fibrillation is warfarin when the risk of thrombosis is
      high, and warfarin or aspirin when the thrombotic risk is moderate. When the INR
      cannot be maintained within the desired therapeutic range, it is best to stick
      with dabigatran.

PMID- 24669382
TI  - Glycopyrronium for inhalation. COPD: another antimuscarinic with cardiac adverse
      effects that require monitoring.
AB  - The most effective way of slowing chronic obstructive pulmonary disease (COPD)
      progression is to eliminate exposure to the inhaled triggering factor, which is
      usually tobacco smoke. At best, inhaled bronchodilators have only a limited
      impact on the symptoms of COPD. In the absence of a better alternative,
      salbutamol, a beta-2 agonist, or ipratropium, an antimuscarinic, are tried first,
      despite their adverse effects. "Long-acting" beta-2 agonists are an option for
      patients with permanent symptoms, especially dyspnoea that disrupts sleep.
      Glycopyrronium, a long-acting antimuscarinic, is authorised in the European Union
      for maintenance treatment of adults with COPD. Clinical evaluation does not
      include any trials versus salbutamol. It is based on three trials, in a total of
      2051 patients that compared glycopyrronium versus placebo and sometimes versus
      tiotropium, another long-acting inhaled antimuscarinic. Mortality rates were
      similar in the different arms of these trials. There was no difference in
      efficacy between glycopyrronium and tiotropium. In two of these trials, which
      lasted at least 26 weeks, "serious" cardiac adverse events were more frequent
      with glycopyrronium than with placebo or tiotropium. However, the number of
      events was too small to determine the precise cardiac harms associated with
      glycopyrronium. The European Medicines Agency has therefore asked for a specific
      registry to be created. The adverse effect profile of glycopyrronium appears
      similar to that of inhaled antimuscarinics, including atropinic disorders and
      upper respiratory infections. The inhaler is simple to use and does not require
      hand-breath coordination. In practice, glycopyrronium does not provide a
      therapeutic advantage in the treatment of patients with COPD. When an inhaled
      long-acting drug is contemplated, it is best to choose a beta-2 agonist
      (formoterol or salmeterol), used either continuously or on demand.

PMID- 24669383
TI  - Abiraterone and metastatic prostate cancer: delays pain onset, cytotoxic therapy,
      and possibly death.
AB  - When metastatic prostate cancer progresses despite androgen suppression but
      symptoms do not yet warrant cytotoxic therapy, abiraterone appears to prolong
      overall survival and to delay the onset of some cancer-related symptoms. But
      beware of cardiac and hepatic adverse effects that are inadequately documented.

PMID- 24669384
TI  - Bacillus Calmette-Guerin and bladder cancer: helpful packaging.
AB  - There are no randomised controlled trials comparing the BCG RIVM strain (BCG
      medac) versus the BCG Connaught strain (Immucyst), but the packaging of BCG-medac
      is far more complete than that of immucyst.

PMID- 24669385
TI  - INN common stem: -zomib.

PMID- 24669386
TI  - Atypical neuroleptics: compulsive disorders.
AB  - Compulsive disorders are known adverse effects of dopamine agonists. Atypical
      neuroleptics (amisulpride, aripiprazole, olanzapine, paliperidone, quetiapine and
      risperidone) have also been implicated in cases of pathological gambling,
      hypersexuality, and compulsive eating and shopping, with sometimes serious social
      and familial consequences. The compulsive disorders improved or ceased when the
      neuroleptic was withdrawn or replaced. Patients must be informed of these
      possible adverse effects and monitored for behavioural changes. If such disorders
      occur, they can be managed by withdrawing the drug, reducing the dosage, or
      switching to another neuroleptic.

PMID- 24669387
TI  - Etoricoxib: a French review of adverse effects.
AB  - Peripheral oedema, and serious gastrointestinal, cardiovascular and cutaneous
      disorders.

PMID- 24669388
TI  - Pregabalin: cardiac adverse effects.
AB  - Rhythm and conduction disorders, heart failure, even at low doses.

PMID- 24669389
TI  - Recurrent uncomplicated cystitis in women: allowing patients to self-initiate
      antibiotic therapy.
AB  - Acute uncomplicated cystitis is a lower urinary tract infection occurring in the
      absence of anatomic or functional abnormalities of the urinary tract or any other
      complicating factors.The organism responsible is often an enterobacterium,
      especially Escherichia coli. What is the role of antibiotic therapy for non
      pregnant women with recurrent acute uncomplicated cystitis? We reviewed the
      available evidence using the standard Prescrire methodology. A single oral dose
      of fosfomycin trometamol is the antibiotic of choice for treating an episode of
      acute uncomplicated cystitis. Alternative antibiotics are certain
      fluoroquinolones or co-trimoxazole (a fixed-dose combination of sulfamethoxazole
      and trimethoprim). For recurrent acute uncomplicated cystitis, cranberry juice
      has modest efficacy in reducing the frequency of episodes. A number of non-drug
      measures are typically proposed, although their effects are unproven: drinking
      sufficient fluids and urinating regularly; urinating after sexual intercourse;
      and avoiding spermicides. The strategy that results in the lowest antibiotic
      exposure is a short course of antibiotics for each episode of urinary tract
      infection, initiated as soon as clinical symptoms appear. Long-term antibiotic
      therapy is sometimes offered. According to one systematic review, women taking
      long-term prophylactic antibiotic therapy had about 6 times fewer clinical
      recurrences than with placebo. According to one randomised trial, 3 g of
      fosfomycin trometamol taken as a single dose every ten days reduced the frequency
      of recurrence, resulting in 0.14 episodes of infection per year on average versus
      about 3 episodes with placebo (p < 0.001). The amount of antibiotic used when
      fosfomycin trometamol is taken every 10 days for 6 months is equivalent to
      treatment of 18 acute episodes of cystitis. When cystitis appears to be
      associated with sexual intercourse, two small randomised trials suggest that
      routine postcoital antibiotic treatment is more effective than placebo and as
      effective as long-term antibiotic therapy. Adverse effects, some of which can be
      serious, depend on the antibiotic used. The development of resistance among
      enterobacteria is one argument for limiting the use of antibiotics, in order to
      preserve their efficacy in serious infections. In practice, the strategy that
      uses the fewest antibiotics is to treat each episode as soon as the first
      clinical symptoms appear. Cases in which the frequency of recurrence warrants
      regular antibiotic prophylaxis are rare. The optimal antibiotic regimen in these
      cases has not been determined, either in clinical trials or by consensus.

PMID- 24669390
TI  - Asthma in pregnancy: drugs of choice and drugs to avoid.

PMID- 24669391
TI  - Drugs to avoid during pregnancy: omalizumab and montelukast, too many
      uncertainties.

PMID- 24669392
TI  - Generics: keep a balanced view.
AB  - Once the different kinds of commercial protection (patents, etc.) granted to the
      manufacturer of an "originator" drug have expired, the drug in question may be
      copied by other companies. These copies are known as generics. The
      characteristics and pharmaceutical quality of generics are governed by
      international standards. The marketing authorisation procedure for generic drugs
      dispenses with preclinical and clinical trials, which already exist for the
      originator drug. In contrast, proof of bioequivalence must be provided. In
      practice, this means demonstrating that the effects of the generic are similar
      (but not necessarily identical) to those of the originator drug. Slight
      differences between a generic and its brand-name counterpart are allowed,
      provided they do not markedly affect the efficacy or adverse effect profile in
      comparison to the originator drug. The accepted degree of difference between a
      generic and the original brand-name drug is the same as the acceptable difference
      between two batches of the originator drug. The rules governing generic
      manufacturing conditions are identical to those applying to originator drugs. And
      issues raised by drug production abroad, particularly to Asian countries, apply
      to originator just as much as to generic drugs. Generics represent a significant
      source of financial savings for society. In France, various measures have been
      introduced to encourage doctors, pharmacists and patients, respectively, to
      prescribe, dispense and use generics. Criticisms of the efficacy or quality of
      generics are often unfounded and sometimes deliberately orchestrated. Smear
      campaigns conducted by drug companies that market originator drugs, and also by
      some healthcare professionals, sow confusion, to the detriment of generic use.
      There is no tangible proof that generics are less safe than originator drugs,
      provided they are chosen wisely, taking into account factors such as their
      packaging quality. It is up to healthcare professionals to decide when a generic
      is appropriate. Ideally, the doctor should prescribe using the international
      nonproprietary name (INN), leaving it up to the pharmacist to choose the generic
      best suited to the patient.

PMID- 24669394
TI  - Haptic exploration in elementary school age children.
AB  - Haptic exploration, or active touch, is a perceptual modality that has
      demonstrated therapeutic potential for elementary age children but is not
      commonly studied with this age group. The aim of this exploratory study was to
      discover the characteristics of haptic scanning that are associated with
      efficiency and accuracy in a shape matching task. The study tasks were designed
      to resemble common visual perception tests, but in a haptic form using wooden
      shapes. Children ages 6 years, 6 months to 9 years, 6 months (N = 25), and adults
      (N = 25) engaged in shape matching tasks that involved either cross-modal (haptic
      with vision) or unimodal (haptic only) exploration. Video recordings were
      analyzed and four types of haptic strategies were identified that were
      significantly related to both age and correctness of response: the simultaneous
      use of two hands was the highest level and the use of one hand was the lowest.
      The findings are discussed in terms of attention capacity and ability to use
      points of reference.

PMID- 24669393
TI  - The art and science of resilience.

PMID- 24669395
TI  - Mothers with chronic disease: a comparison of parenting in mothers with systemic
      sclerosis and systemic lupus erythematosus.
AB  - This study compared parenting ability in mothers with systemic sclerosis (SSc)
      and systemic lupus erythematosus (SLE), two chronic, autoimmune, connective
      tissue diseases that primarily affect women. Seventy-four mothers with SSc and 68
      mothers with SLE completed self-report questionnaires on demographic
      characteristics, pain, fatigue, occupational performance, and parenting. Results
      showed that mothers with SSc were slightly older, were more educated, and had
      decreased occupational performance. Mothers with SLE had more pain and fatigue.
      There were no significant differences between mothers with SSc and SLE who had
      children 5 years of age and younger. However, there were significant differences
      between the mothers with SSc and SLE who had children aged 6 to 18 years on four
      items on the Parenting Disability Index: playing games with child, getting up
      with child during the night, keeping child out of unsafe situations, and helping
      child solve personal/social problems. These differences may be due to differences
      in the levels of pain, fatigue, and occupational performance, possibly stemming
      from differences in disease manifestations.

PMID- 24669396
TI  - Hollywood takes on intellectual/ developmental disability: cinematic
      representations of occupational participation.
AB  - Adults with intellectual/developmental disability (IDD), and their occupational
      participation, are vastly under-represented in Hollywood films. Because films
      often provide individuals' only experience of people with IDD, cinematic
      representations can influence audience perceptions. Thus, films can help inform
      public perceptions about desired and appropriate occupational participation for
      people with IDD, potentially impacting their access to meaningful occupational
      participation and achievement of occupational potential. Accordingly, this
      research examined occupational portrayals of adults with IDD in contemporary
      Hollywood films. Occupational portrayals, as defined here, refer to
      representations of the dynamic process of the person participating in
      occupation(s) in a context. Grounded theory methods guided coding and analysis of
      qualitative data collected from eight contemporary films using an occupation
      focused tool. Two major, striking themes emerging from the qualitative analysis-
      infantilization and simplification of participation in complex occupations (with
      three associated sub-themes)--are discussed. Implications of the findings and
      future research directions are considered.

PMID- 24669397
TI  - Occupational competence strategies in old age: a mixed-methods comparison between
      Hispanic women with different levels of daily participation.
AB  - In this pilot study, we explored the difference in the use of occupational
      competence strategies for daily participation between more active and less active
      older Hispanic women. Twenty-nine women who were 70 and older and lived alone
      participated in this study. We used a mixed-methods design by which the principal
      investigator administered a tool to measure participation restrictions during the
      quantitative phase and conducted in-depth interviews with a subsample in the
      qualitative phase. More active women predominantly used transportation resources,
      emotional social support, and spirituality to support participation in life
      activities. Less active women used more practical social support, assistive
      technology, and environmental modifications. Personal facilitators seemed to
      directly modify these strategies. These results suggest that older women with
      different activity levels use distinct internal and external resources to
      maintain or enhance daily participation. Future studies should explore whether
      these resources remain consistent across gender, living status, and ethnicity.

PMID- 24669398
TI  - Participation of young adults with high-functioning autism in Taiwan: a pilot
      study.
AB  - This pilot study aimed to investigate the activity participation of young adults
      with high-functioning autism (HFA) living in Taiwan. Eleven young adults with
      HFA, their caring adults, and 11 matched typically developing youth were
      recruited across Taiwan. The Adolescent and Young Adult Participation Sort
      Taiwanese version (AYAPS-T) was administered to all three groups to compare the
      activity participation. In addition, youth with HFA identified activities in
      which they desired to participate and barriers hindering their participation. The
      results of this study suggest that youth with HFA had lower participation rates
      in activities across different domains than their typically developing peers.
      Youth with HFA were able to identify the activities they desired to do and the
      barriers hindering their participation. No significant differences in
      participation were found between the results reported by the caring adults and
      youth with HFA. Occupational therapy practitioners may work on eliminating the
      personal and environmental barriers that impede participation as youth with HFA
      transition out of secondary school.

PMID- 24669399
TI  - Improve your balance by strengthening your core. Your abdominal, back, and hip
      muscles can help you avoid falls.

PMID- 24669400
TI  - Ask the doctor.  I've heard that extra potassium can improve my blood pressure. 
      What do you think?

PMID- 24669401
TI  - Ask the doctor.  Is it true that B vitamins can reduce my risk of Alzheimer's
      disease and other types of dementia?

PMID- 24669402
TI  - Protect your memory and thinking skills.  Keeping your blood sugar level in check
      may help ward off dementia.

PMID- 24669403
TI  - Five easy ways to start exercising. Get moving by changing your thinking and
      working exercise into daily activity.

PMID- 24669404
TI  - New statin guidelines: do they apply to you?

PMID- 24669405
TI  - Speaking two languages protects thinking skills.

PMID- 24669406
TI  - Philosophy shift on the risks of being overweight.

PMID- 24669407
TI  - Interoceptors in the anterior byssal retractor muscle of Mytilus edulis L.

PMID- 24669408
TI  - Epidemic field investigation as applied to allegations of chemical, biological,
      or toxin warfare.
AB  - It is proposed that the established epidemiologic framework normally used for
      investigation of civilian epidemics can usefully be adapted to provide a more
      structured approach to future investigations of allegations of chemical,
      biological, or toxin warfare. Using this framework, investigations of such
      allegations during the past decade are reviewed. These investigations took place
      during the yellow rain affair in Laos and Kampuchea, the Iran-Iraq war, and the
      Iraq-Kurd war. Further allegations are likely and will require investigation.

PMID- 24669409
TI  - Evaluation of Electronic Medical Record Administrative data Linked Database
      (EMRALD).
AB  - BACKGROUND: Primary care electronic medical records (EMRs) represent a
      potentially rich source of information for research and evaluation. OBJECTIVE: To
      assess the completeness of primary care EMR data compared with administrative
      data. STUDY DESIGN: Retrospective comparison of provincial health-related
      administrative databases and patient records for more than 50,000 patients of 54
      physicians in 15 geographically distinct clinics in Ontario, Canada, contained in
      the Electronic Medical Record Administrative data Linked Database (EMRALD).
      METHODS: Physician billings, laboratory tests, medications, specialist
      consultation letters, and hospital discharges captured in EMRALD were compared
      with health-related administrative data in a universal access healthcare system.
      RESULTS: The mean (standard deviation [SD]) percentage of clinic primary care
      outpatient visits captured in EMRALD compared with administrative data was 94.4%
      (4.88%). Consultation letters from specialists for first consultations and for
      hospital discharges were captured at a mean (SD) rate of 72.7% (7.98%) and 58.5%
      (15.24%), respectively, within 30 days of the occurrence. The mean (SD) capture
      within EMRALD of the most common laboratory tests billed and the most common
      drugs dispensed was 67.3% (21.46%) and 68.2% (8.32%), respectively, for all
      clinics. CONCLUSIONS: We found reasonable capture of information within the EMR
      compared with administrative data, with the advantage in the EMR of having actual
      laboratory results, prescriptions for patients of all ages, and detailed clinical
      information. However, the combination of complete EMR records and administrative
      data is needed to provide a full comprehensive picture of patient health
      histories and processes, and outcomes of care.

PMID- 24669410
TI  - Specialist participation in healthcare delivery transformation: influence of
      patient self-referral.
AB  - BACKGROUND: Improving coordination of care and containing healthcare costs are
      prominent goals of healthcare reform. Specialist involvement in healthcare
      delivery transformation efforts like Accountable Care Organizations (ACOs) is
      necessary to achieve these goals. However, patients' self-referrals to
      specialists may undermine care coordination and incur unnecessary costs if
      patients frequently receive care from specialists not engaged in such healthcare
      delivery transformation efforts. Additionally, frequent self-referrals may also
      diminish the incentive for specialist participation in reform endeavors like ACOs
      to get access to a referral base. OBJECTIVE: To examine recent national trends in
      self-referred new visits to specialists. STUDY DESIGN: A descriptive cross
      sectional study of new ambulatory visits to specialists from 2000 to 2009 using
      data from the National Ambulatory Medical Care Survey. METHODS: We calculated
      nationally representative estimates of the proportion of new specialist visits
      through self-referrals among Medicare and private insurance beneficiaries. We
      also estimated the nationally representative absolute number of self-referred new
      specialist visits among both groups of beneficiaries. RESULTS: Among Medicare and
      private insurance beneficiaries, self-referred visits declined from 32.2% (95%
      confidence interval [CI], 24.0%-40.4%) to 19.6% (95% CI, 13.9%-23.3%) and from
      32.4% (95% CI, 27.9%-36.8%) to 24.1% (95% CI,18.8%-29.4%), respectively. Hence,
      at least 1 in 5 and 1 in 4 new visits to specialists among Medicare and private
      insurance beneficiaries, respectively, are self-referred. CONCLUSIONS: The
      current considerable rate of self-referred new specialist visits among both
      Medicare and private insurance beneficiaries may have adverse implications for
      organizations attempting to transform healthcare delivery with improved care
      coordination.

PMID- 24669411
TI  - Optimal management of diabetes among overweight and obese adults.
AB  - OBJECTIVE: To explore potential weight-related disparities in the quality of care
      for adults with diabetes in a large managed care health plan according to
      recommended quality indicators. DESIGN: Cross-sectional analysis. METHODS: A
      total of 164,721 Kaiser Permanente Southern California members aged 18 to 75
      years with diabetes who had 1 or more health encounters with a weight and height
      measurement between July 1, 2007, and June 30, 2008, were identified. The 9
      Healthcare Effectiveness Data and Information Set (HEDIS) quality-of-care
      measures were examined: 4 screening measures (glycated hemoglobin [A1C], retinal
      examination, lipids, and nephropathy) and 5 control measures (2 for A1C, 2 for
      blood pressure, and 1 for low-density lipoprotein cholesterol [LDLC]), using data
      extracted from electronic health records (EHRs). Weight and height from the EHR
      were used to calculate body mass index (BMI). Adjusted odds ratios and 95%
      confidence intervals were calculated to examine the association between BMI
      categories and HEDIS quality-of-care measures. RESULTS: Among individuals with
      diabetes, 12% were in the healthy-weight category, 30% were overweight, and 28%,
      17%, and 14% were in obese categories I, II, and III, respectively. Overweight
      and obese individuals were more likely than their healthy-weight counterparts to
      have screening measures performed. However, among those tested or screened,
      overweight and obese individuals were less likely to have their A1C and blood
      pressure controlled. LDL-C control increased as BMI increased. CONCLUSIONS: These
      findings highlight the need for interventions to improve glycemic and blood
      pressure control among overweight and obese patients with diabetes.

PMID- 24669413
TI  - [Asthma phenotype endotype].

PMID- 24669412
TI  - Why Are Medicare and commercial insurance spending weakly correlated?
AB  - OBJECTIVE: To investigate the source of the weak correlation across geographic
      areas between Medicare and private insurance spending. STUDY DESIGN:
      Retrospective, descriptive analysis. METHODS: We obtained Medicare spending data
      at the hospital referral region (HRR) level for 2007 from the Dartmouth Atlas,
      and commercial claims from large employers for 2007 from the Truven MarketScan
      Database. We constructed county-level data on hospital market structure from
      Medicare patient flows and obtained county-level data on the Medicare wage index
      from the Centers for Medicare & Medicaid Services website. We aggregated these
      sources to the HRR level. We decomposed Medicare and private spending into 2
      components: price and volume. We also decomposed Medicare and private prices into
      2 components: a common measure of cost and a sector-specific markup. We computed
      correlations between Medicare and private prices and volumes, and the correlation
      of each sector's price and volume with cost and markup. RESULTS: We found that
      Medicare and private prices are strongly positively correlated, largely because
      both are keyed off of common costs. Consistent with previous work, we found that
      Medicare and private volumes are strongly positively correlated as well.
      CONCLUSIONS: The weak correlation between Medicare and private spending is
      consistent with these 2 empirical regularities. It is mathematically due to
      negative correlations between each sector's price and the other sector's volume.
      In particular, we found that private prices have important spillover effects on
      Medicare volume. Future research on the effects of competition should take
      account of this phenomenon.

PMID- 24669414
TI  - Phytochemicals: the future of radiation induced mucositis prevention.

PMID- 24669415
TI  - [Introduction].

PMID- 24669416
TI  - [Free will or imposed? Bioneuropsychologic basis of will in the human life
      cycle].

PMID- 24669417
TI  - [Neurobiological substrates support human "I"].

PMID- 24669418
TI  - [Genetic aging of the brain].

PMID- 24669419
TI  - [Development of theory of mind in children--neurobiological and socio-cultural
      conditions].

PMID- 24669421
TI  - [The brain and sleep].

PMID- 24669420
TI  - [Left-handedness--blessing or curse?].

PMID- 24669422
TI  - [Stress--builder or destroyer of cognitive processes?].

PMID- 24669423
TI  - [Neurologic conditions for partner selection].

PMID- 24669424
TI  - [Power of the mind or excellent doping].

PMID- 24669425
TI  - [Cerebellum--its role in development of cognitive and aging functions].

PMID- 24669426
TI  - [Secular and religious deliberations around the topic of organ donation].

PMID- 24669427
TI  - [Will in the processing of recovering life energy, study of a case of nervous
      system disorders in the aftermath of cardiac crisis].

PMID- 24669428
TI  - [Adjustment of intercellular communication via extracellular ATP in the nervous
      system].

PMID- 24669429
TI  - [Influence of physical activity on cognitive function].

PMID- 24669430
TI  - [Qualia as a result of culturally biological determinants].

PMID- 24669431
TI  - [Impact of early life experiences on development of the nervous system and
      patterns of response from the perspective of potential risks. How to repair the
      damage--does psychotherapy change the brain?].

PMID- 24669432
TI  - [Is qualia necessary?].

PMID- 24669433
TI  - [The role of dopamine in motivational processes and the development of
      addiction].

PMID- 24669434
TI  - [Do plants have awareness?].

PMID- 24669435
TI  - [The principle of confidentiality and reflection in world thought. Against the
      current to the source--our ideas].

PMID- 24669436
TI  - [What kind of consolation neurocognition offers].

PMID- 24669437
TI  - [Influence of the magnetic field and glial cells on cognitive function.
      Partnership or rivalry?].

PMID- 24669438
TI  - [Biofeedback as an effective method for treatment of cognitive deficits in terms
      of theory of mind].

PMID- 24669439
TI  - What is qualitative research?

PMID- 24669440
TI  - We get biased on things that make sense.

PMID- 24669441
TI  - Histoplasma capsulatum in New England: a case study.

PMID- 24669442
TI  - Cost-benefit and effectiveness analysis of rapid testing for MRSA carriage in a
      hospital setting.
AB  - A cost-effectiveness analysis was conducted comparing the polymerase chain
      reaction assay and traditional microbiological culture as screening tools for the
      identification of methicillin-resistant Staphylococcus aureus (MRSA) in patients
      admitted to the pediatric and surgical intensive care units (PICU and SICU) at a
      722 bed academic medical center. In addition, the cost benefits of identification
      of colonized MRSA patients were determined. The cost-effectiveness analysis
      employed actual hospital and laboratory costs, not patient costs. The actual cost
      of the PCR assay was higher than the microbiological culture identification of
      MRSA ($602.95 versus $364.30 per positive carrier identified). However, this did
      not include the decreased turn-around time of PCR assays compared to traditional
      culture techniques. Patient costs were determined indirectly in the cost-benefit
      analysis of clinical outcome. There was a reduction in MRSA hospital-acquired
      infection (3.5 MRSA HAI/month without screening versus 0.6/month with screening
      by PCR). A cost-benefit analysis based on differences in length of stay suggests
      an associated savings in hospitalization costs: MRSA HAI with 29.5 day median LOS
      at $63,810 versus MRSA identified on admission with 6 day median LOS at $14,561,
      a difference of $49,249 per hospitalization. Although this pilot study was small
      and it is not possible to directly relate the cost-effectiveness and cost-benefit
      analysis due to confounding factors such as patient underlying morbidity and
      mortality, a reduction of 2.9 MRSA HAI/month associated with PCR screening
      suggests potential savings in hospitalization costs of $142,822 per month.

PMID- 24669443
TI  - Staphylococcus, not MRSA? A final report of carriage and conversion rates in
      nursing students.
AB  - OBJECTIVE: To evaluate and characterize staphylococcal carriage, possibly
      including methicillin-resistant Staphylococcus aureus (MRSA), and conversion
      rates in nursing students across clinical semester rotations and to describe risk
      factors. DESIGN: A prospective longitudinal cohort design with six times of
      measurement. Data collected August 2010 to May 2012. Institutional Review Board
      approval (2010F5693). SETTING: Texas State University, San Marcos, TX.
      PARTICIPANTS: Eighty-seven nursing students. INTERVENTIONS: A positive MRSA swab
      was considered an end point for participation. Intervention offered was bactroban
      (mupirocin) for nasal decolonization and an oral antibiotic, doxycycline; follow
      up post treatment collection sample was done to verify decolonization prior to
      next clinical rotation. MAIN OUTCOME MEASURES: Screening for Staphylococcus
      aureus and MRSA identification; confirmation and antibiotic susceptibility by
      Vitek 2; self-administered questionnaires delineating demographics and risk
      factors; panel logistic regression models by Stata version 13. RESULTS: MRSA
      colonization did not increase. S. aureus incidence was 17.7 - 26.4%.
      Staphylococcal species incidence other than S. aureus increased (9.2 - 82.3%).
      The following odds ratio (OR) associations were found to be statistically
      significant: boil or skin infections with S. aureus (OR = 2.94, p < .01), working
      or volunteering in a healthcare facility odds with species other than S. aureus
      (OR = 4.41, p < .01) and gym and sports facilities odds with S. other (OR 2.45, p
      < .01). The most frequently occurring species at Wave 5 was S. hominis (21
      isolates) while the most frequently occurring species at Wave 6 was S.
      epidermidis (25 isolates). CONCLUSIONS: MRSA colonization did not increase during
      longitudinal study. S. aureus colonization remained fairly stable throughout the
      study (17 - 26%). Species colonization with non S. aureus species (e.g. S.
      hominis, S. epidermis, S. haemolyticus) increased significantly (9.2 - 82.3%)
      during clinical rotations. Knowledge of infection control and compliance may have
      contributed to an absence of MRSA colonization; however, the colonization by
      other staphylococci has been shown to be a risk factor for MRSA acquisition.

PMID- 24669444
TI  - A survey study of benefits and limitations of using CellaVision DM96 for
      peripheral blood differentials.
AB  - In most clinical laboratories, hematologists rely on the microscopic analysis of
      stained blood films to accurately classify cells, aiding in the diagnosis and
      monitoring of a variety of disorders and conditions. Use of the microscope,
      although considered the gold standard in performing white blood cell
      differentials, presents a variety of limitations Digital image technology can
      facilitate a variety of essential job functions in clinical hematology such as:
      consulting with colleagues, improving training, referencing an abnormal cell, and
      utilizing archived images for quality assurance and competency assessment. A
      questionnaire was developed to survey medical laboratory professionals about
      their perceptions regarding the benefits and limitations for using digital images
      in clinical hematology. The questionnaire was sent in March 2012 to an entire
      list of 81 current CellaVision DM96 (CellaVision AB, Sweden) consumers. A
      response rate of 46% was obtained. Background information on participants, 5
      point Likert scale averages, percentage agreement (strongly agree and agree), and
      disagreement (strongly disagree and disagree) were calculated and analyzed. The
      benefits of using the CellaVision DM96 rated the strongest by respondents
      included: decreased eyestrain, consistency among patient results and advantages
      in training personnel. Respondents reported notable limitations as being:
      restrictions with accurately estimating platelets and red cell morphology.
      Digital image software is currently being utilized in preclinical and clinical
      hematology and offers potential benefits. With upgrades in slide scanning
      features and improved capabilities to view platelet and red cell morphology, a
      transition to digital image technology from the conventional method for
      performing peripheral blood cell differentials is possible.

PMID- 24669445
TI  - Molecular diagnosis of sexually transmitted infections: a diverse and dynamic
      landscape.

PMID- 24669446
TI  - More than just a test result: molecular screening of human papilloma virus for
      contemporary management of cervical cancer risk.

PMID- 24669447
TI  - Epidemiological and clinical rationale for screening and diagnosis of Mycoplasma
      genitalium infections.

PMID- 24669448
TI  - Trichomonas vaginalis: common, curable and in the diagnostic spotlight.

PMID- 24669449
TI  - [People with limited autonomy and decision-making ability--Health and Social Care
      Inspectorate should take a stand].

PMID- 24669450
TI  - [Measures directed against snuffing. Smoking is still "the worst bad guy"].

PMID- 24669451
TI  - [Suicide among immigrants increases. It increased 10.3 percent in 2012, among
      Swedish-born 2.8 per cent].

PMID- 24669452
TI  - [Blow out hemorrhage in the head and neck region in practice. Suggestions for
      what we can, may and should do].

PMID- 24669453
TI  - [Language assessments at child health services develops positively. More common
      with evidence-based methods].

PMID- 24669454
TI  - [Camptocormia and pleurothotonus: rare side effects of neuroleptics].

PMID- 24669455
TI  - [Pheochromocytoma can easily be missed in an unusual symptomatology. Hypotension
      and syncope were interpreted as orthostatism].

PMID- 24669456
TI  - [Sprained ankle].

PMID- 24669457
TI  - [Diuretics cause the most poisonings in Sweden--right?].

PMID- 24669458
TI  - [More rectal palpation!].

PMID- 24669459
TI  - [Physicians who wants to moonlight should choose authorized agencies].

PMID- 24669460
TI  - [The bio terminology group recommends: Dare to nurture our professional language
      ].

PMID- 24669461
TI  - Countdown to ICD-10. Providers have a long to-do list between now and October.

PMID- 24669462
TI  - Running on EMPI. Health information exchanges and the ONC keep trying to find the
      secret sauce of patient matching.

PMID- 24669463
TI  - A father's reflections.

PMID- 24669464
TI  - Staffing levels still "dangerous".

PMID- 24669465
TI  - "Nursing schools should back speak out safely to support students".

PMID- 24669466
TI  - "Gather feedback to build up your evidence for revalidation".

PMID- 24669467
TI  - NICE guidance on giving intravenous fluids.

PMID- 24669468
TI  - Do zero tolerance policies deskill nurses?
AB  - Although much has been written about patient aggression, its management remains
      problematic, with many healthcare providers adopting a "zero tolerance" approach.
      This article uses case studies to discuss: the negative implications associated
      with this policy; the background to patient aggression and other "challenging"
      behaviours; how nurses, midwives and other health professionals respond to them;
      and how they can reclaim their professional role in this important aspect of
      patient care.

PMID- 24669469
TI  - What is the purpose of liver function tests?
AB  - The liver is the body's largest single discrete organ. It has four major
      functions: metabolism and synthesis; excretion; storage; and the detoxification
      of potential poisons. These diverse functions mean that a single test does not
      give enough information to assess fully how the liver is functioning; at least
      five different liver function tests are required. This article, part 2 in a four
      part series, discusses the information on acute and chronic liver disease that
      these tests can provide, and how disease affects liver function.

PMID- 24669470
TI  - Peer support to assist in transition to adult services.
AB  - A peer support worker employment initiative was developed to help young service
      users with the transition from child and adolescent to adult mental health
      services, an area that needs improving nationally. This article describes how the
      initiative was set up and its effectiveness.

PMID- 24669471
TI  - Antibiotics for lower urinary tract infection in children.

PMID- 24669472
TI  - Venous thromboembolism risk with glucocorticoid use.

PMID- 24669473
TI  - 60 seconds with Sean Duggan.

PMID- 24669474
TI  - From classroom to frontline.

PMID- 24669475
TI  - Be clear about the purpose of rounds.

PMID- 24669476
TI  - Lessons for nurses from Nelson Mandela.

PMID- 24669477
TI  - The attainment of professional autonomy through collective action.

PMID- 24669478
TI  - "Fearless and fiery". First chair of the University of Michigan Professional
      Nurse Council passes.

PMID- 24669479
TI  - Open enrollment for Medicaid expansion starts April 1, 2014.

PMID- 24669480
TI  - The growing inflation of Michigan's hospital charges: how much more can patients
      pay?

PMID- 24669481
TI  - Nurses face weather extremes for their patients.

PMID- 24669482
TI  - Workplace violence: MNA partners with Wayne State University, implements three
      pronged strategy to address growing problem.

PMID- 24669483
TI  - LaShon Hart, MSN, RN.

PMID- 24669484
TI  - [Care of frail elderly patients--evidence-based approach exists].

PMID- 24669485
TI  - [Gender imbalance. Why so few future (male) reviewers?].

PMID- 24669486
TI  - [Proposal for a national security strategy--it's a good start].

PMID- 24669487
TI  - [Aminoglycosides are effective--but oto- and nephrotoxic. Knowledge base from the
      reference group for antibiotic issues on benefit-risk with aminoglycosides].

PMID- 24669488
TI  - [Swedish military health care in Afghanistan is top class. Prehospital trained
      anesthetists early in the continuum of care is a foundation].

PMID- 24669489
TI  - [Metastatic spinal cord compression must not be missed. Increased awareness of
      early symptoms enables fast treatment].

PMID- 24669490
TI  - [Free of charge mammography gets more people to the examination. Study in
      Stockholm County shows good efficacy in socioeconomically disadvantaged areas].

PMID- 24669491
TI  - ["Persistent genital arousal disorder" unrelated to sexual desire, difficult to
      treat in women].

PMID- 24669492
TI  - [Hormone replacement therapy with progesterone should be possible to prescribe].

PMID- 24669493
TI  - [National guidelines must be implemented locally].

PMID- 24669494
TI  - [Flammable about smoke].

PMID- 24669495
TI  - [The price of postmodernism].

PMID- 24669496
TI  - [Consumer's psychological processes of hoarding and avoidant purchasing after the
      Tohoku earthquake].
AB  - This study examined psychological processes of consumers that had determined
      hoarding and avoidant purchasing behaviors after the Tohoku earthquake within a
      dual-process model. The model hypothesized that both intentional motivation based
      on reflective decision and reactive motivation based on non-reflective decision
      predicted the behaviors. This study assumed that attitude, subjective norm and
      descriptive norm in relation to hoarding and avoidant purchasing were
      determinants of motivations. Residents in the Tokyo metropolitan area (n = 667)
      completed internet longitudinal surveys at three times (April, June, and
      November, 2011). The results indicated that intentional and reactive motivation
      determined avoidant purchasing behaviors in June; only intentional motivation
      determined the behaviors in November. Attitude was a main determinant of the
      motivations each time. Moreover, previous behaviors predicted future behaviors.
      In conclusion, purchasing behaviors were intentional rather than reactive
      behaviors. Furthermore, attitude and previous behaviors were important
      determinants in the dual-process model. Attitude and behaviors formed in April
      continued to strengthen the subsequent decisions of purchasing behavior.

PMID- 24669497
TI  - [Development of the Coparental Regulation Inventory and cross-sectional analysis
      of mothers' encouragement and criticism].
AB  - We developed the Coparental Regulation Inventory to assess the regulatory
      behavior of the mothers in involving fathers with child rearing. We translated
      and modified the short form of the Parental Regulation Inventory (PRI) for
      Japanese couples in different stages of child rearing. An online questionnaire
      was conducted with mothers (n = 500) and fathers (n = 500) whose youngest child
      was less than 21-years-old. Exploratory factor analysis identified two factors,
      which were labeled "encouragement" and "criticism". The resulting Coparental
      Regulation Inventory (the modified PRI) had high internal consistency and test
      retest reliability. The construct validity of the scale was supported by its
      correlation with parenting alliance, marital satisfaction, and the father's
      involvement. These findings suggest that the scale is an adequate instrument for
      identifying the behaviors of mothers related to coparenting. In addition, we
      examined the frequency of encouragement and criticism used by the mother in
      relation to the child-rearing stage using cross-sectional analysis. In the
      mothers' reports, mothers with infants and children encouraged fathers more than
      mothers with early and late adolescents. Mothers with late adolescents criticized
      fathers less than mothers with infants. In the fathers' reports, mothers gave
      more encouragement to fathers who had infants than at any other age, whereas the
      child's age was not related to mothers' criticism perceived by the fathers.

PMID- 24669498
TI  - [Relationship between self-evaluation of their emotions and subjective adaptation
      to school among junior high school students].
AB  - The effect of self-evaluation of emotions on subjective adaption to school was
      investigated among junior high school students (n = 217: 112 boys, 105 girls) who
      participated in a questionnaire survey. Hierarchical multiple regression analysis
      indicated that for boys "Infringement and maladjustment" differed based on their
      self-evaluation of anger and anxiety. For girls, on the other hand, the self
      evaluation of anger alleviated psychological stress, worsened the "Relationship
      with the teacher" and the "Relationship with the class", whereas self-evaluation
      of anxiety played a role in increasing psychological stress and deteriorating the
      "Relationship with the class." Furthermore, negatively evaluating either anger or
      anxiety heightened the "Motivation for learning" in girls. These results suggest
      that the evaluation of emotions is different in boys and girls and for different
      emotions.

PMID- 24669499
TI  - [Development of skills to report "roughly" and "exactly" with different levels of
      exactness].
AB  - This study examined the development of skills to report with different levels of
      exactness. A total of 62 first-grade children and 58 fourth-grade children were
      asked about numbers and lengths (numeral tasks) and colors and positions of
      objects (nominal tasks) with instructions suggesting different levels of
      exactness, "roughly" or "exactly". In Study 1, the instructions were given as a
      between-subjects factor. The results showed that when the "roughly" instruction
      was given, participants gave approximate answers more frequently than when the
      "exactly" instruction was given especially in the numeral tasks, and older
      children did so more frequently than younger children. In Study 2, the
      instructions were given as a within-subjects factor: a half of participants were
      given "roughly" and then "exactly" instructions, and the others were given the
      instructions in the opposite order. The results showed that younger children
      could change the levels of answers depending on instruction in the numeral tasks
      but not in the nominal tasks, whereas older children could do so in both tasks.
      The results suggest that the skills for reporting with different levels of
      exactness are related not only to cognitive development, but also to the
      linguistic context, such as the tasks and instructions.

PMID- 24669500
TI  - [Development of the Scale of Social Interest for Elementary School Children].
AB  - This study reports the development of The Scale of Social Interest for Elementary
      School Children and examines its reliability and validity. Elementary school
      students of fourth, fifth, and sixth grades responded to provisional items of the
      scale, as well as scales assessing mental health, adaptation to school, and
      sympathy. An exploratory factor analysis was conducted using the provisional
      items. The following three factors, which had also been identified by Kosaka
      (2011), were extracted: feelings of contribution, feelings of belonging to
      society and trust in society, and self-acceptance. Confirmatory factor analysis
      indicated sufficient fitness. The reliability of the scale was confirmed based on
      internal consistency and stability. The predicted relationships among the scale
      and mental health, school adaptation, and sympathy were demonstrated. Based on
      these results, the reliability and validity of the Scale of Social Interest for
      Elementary School Children were confirmed.

PMID- 24669501
TI  - [Dispositional mindfulness modulates automatic transference of disgust into moral
      judgment].
AB  - Previous studies showed that incidental feelings of disgust could make moral
      judgments more severe. In the present study, we investigated whether individual
      differences in mindfulness modulated automatic transference of disgust into moral
      judgment. Undergraduates were divided into high- and low-mindfulness groups based
      on the mean score on each subscale of the Five Facet Mindfulness Questionnaire
      (FFMQ). Participants were asked to write about a disgusting experience or an
      emotionally neutral experience, and then to evaluate moral (impersonal vs. high
      conflict personal) and non-moral scenarios. The results showed that the disgust
      induction made moral judgments more severe for the low "acting with awareness"
      participants, whereas it did not influence the moral judgments of the high
      "acting with awareness" participants irrespective of type of moral dilemma. The
      other facets of the FFMQ did not modulate the effect of disgust on moral
      judgment. These findings suggest that being present prevents automatic
      transference of disgust into moral judgment even when prepotent emotions elicited
      by the thought of killing one person to save several others and utilitarian
      reasoning conflict.

PMID- 24669502
TI  - [Gender differences in measures of mental health associated with a marital
      relationship].
AB  - This study examined gender differences for two measures of mental health as
      related to the quality of the marital relationship. Middle-aged respondents (221
      female; 210 male) rated their marital satisfaction, affection, and communication.
      They also rated their psychological well-being and depression. The correlations
      between marital quality and mental health indicated that for males marital
      quality was more strongly associated with psychological well-being than with
      depression. Females showed no such difference, or their marital quality was
      associated with depression. This implies that for females, depression was a more
      sensitive measure of their mental health related to their husband-wife
      relationship. On the other hand, for males subjective well-being which was
      correlated with self-esteem was a more sensitive measure of their mental health.

PMID- 24669503
TI  - [Post-training N-methyl-D-aspartate receptor blockade facilitates retention of
      acquired spatial memory in rats].
AB  - We investigated the effect of a post-training chronic infusion of N-methyl-D
      aspartate (NMDA) receptor blocker on retention of spatial reference memory in
      rats. In Experiment 1, we trained 4 groups of rats for 4 days (4 trials/ day) in
      the Morris water maze task. In a single probe trial after retention intervals of
      1, 7, 14, and 28 days, the 1-day group showed more goal crossings than shown by
      the other 3 groups. In Experiment 2, a chronic infusion of the NMDA receptor
      antagonist D-2-amino-5-phosphonovaleric acid (D-AP5) or a control vehicle into
      the lateral ventricle was initiated 1 day after the training session, and
      continued for 6 days. In the subsequent probe trial (7 days after training), the
      rats that had received the D-AP5 infusion showed significantly more goal
      crossings than the controls. These findings suggest that an NMDA receptor
      blockade following acquisition facilitates retention of spatial reference memory.

PMID- 24669504
TI  - [Is superstitious behavior more easily acquired by negative reinforcement
      schedules than positive reinforcement schedules? Examinations of the polarity and
      the duration of a consequence].
AB  - This study investigated the effects of positive and negative reinforcement on
      superstitious behaviors. Participants were instructed to produce the word "GOOD"
      on a computer display (positive reinforcement condition) or to remove the word
      "BAD" (negative reinforcement condition) by pressing any of six keys. The words
      GOOD or BAD were presented at fixed-time intervals regardless of the
      participant's responses. In Experiment 1, only participants exposed to the
      negative reinforcement condition acquired superstitious behaviors. However, the
      observed asymmetry may not have been due to the polarity of consequences
      (positive vs. negative) but instead to the amount of time of goal states, because
      the period of the absence of BAD was longer than the period of the presence of
      GOOD. Experiment 2 varied the duration of word presentations to match the period
      of goal state between the positive and negative reinforcement conditions, and
      found that participants acquired superstitious behaviors equally under the two
      conditions. These results indicate that the duration of a consequence rather than
      its polarity is a critical factor controlling superstitious behaviors. The
      theoretical relationship between superstitious behavior and the illusion of
      control is discussed.

PMID- 24669505
TI  - [Experimental investigation of intergenerational interaction and older adults'
      generativity].
AB  - This study examined the effects of the reactions of younger adukts toward older
      adults on the psychological attributese and behavior of elderly. Participants
      were 34 older male adults aged 60-82 years. They completed a questionnaire on
      generativity before and after the experimental condition, and were also observed
      taking flyers on different topics after the experiment. They were assigned to the
      younger condition or the same generation condition. In both conditions, the
      participants were asked to talk to recipients about experiences from their youth
      and the wisdom they have gained. The recipients responded to the participants in
      either a positive or a neutral way. The results showed that generativity was
      promoted most when the younger recipients responded in a positive manner, whereas
      the neutral reactions of younger recipients led to the inhibition of
      generativity. Younger persons' positive reactions promoted the participants'
      helping behaviors, as indicated by the flyers they took. The present study shows
      increases in the generativity of the elderly following positive reactions from
      younger recipients not only on questionnaires but also in an experimental
      setting.

PMID- 24669506
TI  - Message from the editor: the past, present, and future of IJAHD.

PMID- 24669507
TI  - Age differences in subjective well-being across adulthood: the roles of savoring
      and future time perspective.
AB  - Prior research indicates there are age differences in subjective well-being
      during adulthood, but research on age differences in savoring (up-regulating
      positive emotion) is lacking. Using an online survey (N = 218, adults 18-77),
      this study investigated age differences in subjective well-being and savoring,
      and whether future time perspective (perceived amount of time left to live)
      mediated associations between age and savoring. Results indicated a nonlinear
      effect of age on subjective well-being. Although savoring was associated with
      subjective well-being, age was not directly associated with savoring. However, an
      indirect effect of future time perspective linking age and savoring indicated
      that younger adults reported more perceived time left in life and those
      perceiving more time left in life reported greater savoring. Overall, the results
      do not support savoring as a direct explanatory mechanism for age differences in
      subjective well-being, but future time perspective appears to play an important
      role in indirect associations between age and savoring.

PMID- 24669508
TI  - Aging and social networks in Spain: the importance of pubs and churches.
AB  - We examined whether the social convoy model and socioemotional selectivity theory
      apply in collectivistic cultures by examining the contextual factors which are
      hypothesized to mediate age-related differences in social support in a
      collectivist European country. Five hundred Spanish community-dwelling older
      adults (Mean age = 74.78, SD = 7.76, range = 60-93) were interviewed to examine
      structural aspects of their social networks. We found that age showed highly
      complex relationships with network size and frequency of interaction, depending
      on the network circle and the mediation of cultural factors. Family structure was
      important for social relations in the inner circle, while pubs and churches were
      important for peripheral relations. Surprisingly, pub attendance was the most
      important variable for maintenance of social support of peripheral network
      members. In general, the results support the applicability of the social convoy
      and socioemotional selectivity constructs to social support among Spanish older
      adults.

PMID- 24669509
TI  - Age differences in autobiographical memories of negative events.
AB  - This study examined whether older adults recollect autobiographical memories of
      negative events so as to minimize unpleasant emotions to a greater extent than do
      younger adults. A sample of healthy older adults (N = 126) and younger adults (N
      = 119) completed the Autobiographical Memory Questionnaire and a measure of PTSD
      symptoms in response to their most negative recalled event. Results supported the
      hypothesis that older adults rated their negative memories as having: 1) less of
      a sense of traveling back to the time the event occurred, 2) less associated
      visceral emotional reactions, 3) fewer associated negative emotions, and 4) fewer
      PTSD symptoms, all relative to younger adults. In addition, older adults
      exhibited higher ratings of belief in accuracy, higher ratings that the memory
      comes as a coherent story, and more associated positive emotions, again all
      relative to younger adults. After controlling for differences between the types
      of events younger and older adults reported and how long ago the event occurred,
      the above age differences remained statistically significant, though the effect
      sizes were attenuated in some cases. These results are consistent in their
      support for the positivity effect, and suggest that older adults modify their
      recollections of negative events in a manner that is emotionally adaptive for
      them.

PMID- 24669510
TI  - How Japanese adults perceive memory change with age: middle-aged adults with
      memory performance as high as young adults evaluate their memory abilities as low
      as older adults.
AB  - The characteristics of self-referent beliefs about memory change with age. The
      relationship between beliefs and memory performance of three age groups of
      Japanese adults was investigated. The beliefs measured by the Personal Beliefs
      about Memory Instrument (Lineweaver & Hertzog, 1998) differed among the age
      groups and between sexes. In most scales, the ratings by middle-aged adults were
      as low as those by older adults, which were lower than those by young adults.
      Women perceived their memory abilities as lower than men's, with no interaction
      between age and sex, suggesting the difference remains across the lifespan. For
      middle-aged adults, the better they performed in cued-recall, free recall, and
      recognition, the lower they evaluated their memory self-efficacy, while few
      relationships were found for other groups. Our results suggest that cognitive
      beliefs change with age and that investigating the beliefs of the middle-aged
      adults is indispensable to elucidate the transition of beliefs.

PMID- 24669511
TI  - Not all in the mind.

PMID- 24669512
TI  - The promise of better provision.

PMID- 24669513
TI  - When is it right to take consent to treatment out of the woman's hands?

PMID- 24669514
TI  - RCM surveys find worrying flaws in postnatal mental health care.

PMID- 24669515
TI  - Striving for better maternal mental health.
AB  - Mental health is an integral part of health and a state of wellbeing. The concept
      of 'parity of esteem' increases awareness that mental health needs to be treated
      as seriously as physical health. During the childbirth continuum, women and their
      partners can be at increased risk of mental health problems; therefore it is
      important to embrace the 'parity of esteem' concept. This article highlights
      links between mental and physical health problems and discusses the vital role
      that midwives can play in promoting better maternal mental health. It considers
      the challenges this can present to midwives and maternity services.

PMID- 24669516
TI  - Too afraid to push: dealing with fear of childbirth.
AB  - Maternal request for caesarean section in the absence of medical need is an
      ethical and moral dilemma for the NHS. When a woman makes such a request it
      requires careful exploration of the underlying motivation. Many of these women
      will be anxious or fearful of giving birth and require tailored support. The
      provision of an antenatal pathway that acknowledges these fears, focuses on
      enabling coping mechanisms and supports shared decision making can reduce the
      number of requests for a caesarean.

PMID- 24669517
TI  - Developing specialist perinatal mental health services.
AB  - Perinatal mental illness (PMI) represents a significant public health concern
      affecting considerable numbers of pregnant women and mothers of infants.
      Depression and anxiety are key issues; however accurate identification of PMI,
      suitable intervention and provision of adequate services are salient contemporary
      challenges. Coherence in the commissioning of PMI services, appropriate and
      contextually sensitive to the needs of the locality, remains a critical factor in
      the provision of high quality, integrated and seamless care. However, such
      coherence has had difficulty in finding traction, largely as a consequence of
      complex service and organisational structures and commissioning pathways. This
      paper discusses many of the issues that must be considered in the provision of
      high quality PMI services that are sensitive and appropriate for the needs of
      women and their families in the community. An exemplar of the development of a
      local service is discussed in detail.

PMID- 24669518
TI  - How midwives can help with perinatal depression.
AB  - In 2011 a national children's charity led a campaign that identified why help
      with postnatal depression (PND) needed to improve; however PND remains a huge
      problem. Numerous cases are still coming to light where a mother has not sought
      help or has not been given adequate support, with disastrous consequences. Why is
      this still happening and what can health professionals do? Former practising
      midwife and specialist PND counsellor at a charity supporting women and families
      suffering from PND, Joanne Morton discusses why increasing awareness, education
      and understanding of perinatal illness are vital to limit the devastating effects
      of antenatal depression (AND) and PND and how standards of care must improve to
      help mothers in need.

PMID- 24669519
TI  - Perinatal mental health: midwives and health visitors working together.
AB  - The Healthy Child Programme (HCP) focuses on the care offered to pregnant women
      and children in the first five years of life. It is delivered by a range of
      professionals, with the health visitor as lead. Effective delivery of the HCP
      depends on services for children and families being fully integrated, and
      partnership working between different agencies on a local level seems to be the
      key to success. This article focuses on how effective implementation of the HCP
      facilitates the recognition and care of women with anxiety, mild to moderate
      depression and other perinatal mental disorders during both the antenatal period
      and after the birth.

PMID- 24669520
TI  - A healthy ticker... or a good heart?
AB  - The amount of paperwork requiring completion by NHS professionals has increased
      over the years. Some employees feel that is driving them away from client care.
      In this article, one midwife tots up a week's worth of what she describes as 'box
      ticking', and asks: what is the effect of this quantifying trend on the quality
      of care provided for women and families? Does a mark on a page provide a real
      representation of the interactions that have taken place? Whilst acknowledging
      that good documentation is an essential part of care, she questions its
      domination as a reflection of a job well done.

PMID- 24669521
TI  - Examination of the newborn: the key skills. Part 3: the hips.
AB  - Midwives are increasingly performing the examination of the newborn. his article
      considers the importance of the examination of the hips in the screening process.
      The significance of history taking, knowledge of risk factors and the hip
      examination will be explored. The necessity for early detection and treatment of
      hip abnormalities, along with referral pathways that the National Screening
      Committee quires will be highlighted. The impact of late detection of
      developmental dysplasia of the hip (DDH) on the lives of families and children
      will also be considered.

PMID- 24669522
TI  - Midwifery basics: midwifery supervision. 6. The role of the supervisor of
      midwives in an investigation.

PMID- 24669523
TI  - How to grow a student conference.

PMID- 24669525
TI  - Oncology nurses are the first-line guardians of patient safety.

PMID- 24669524
TI  - A clash of paradigms.

PMID- 24669526
TI  - We need strong, visionary, and innovative leaders to transform cancer care.

PMID- 24669527
TI  - Passing up paper: Electronic systems improve safety in chemotherapy ordering and
      management.

PMID- 24669528
TI  - How is your workplace improving the safety of chemotherapy administration?

PMID- 24669529
TI  - No ordinary pill.

PMID- 24669530
TI  - How can healthcare providers ensure patients adhere to oral therapies?

PMID- 24669531
TI  - Cancer's infectious counterpart.

PMID- 24669532
TI  - How do ONS PEP resources help you prevent infection in your practice?

PMID- 24669533
TI  - U.S. survey reports oral chemotherapy practice and safety patterns.

PMID- 24669534
TI  - Despite shaky start, Healthcare.gov closes out 2013 with success.

PMID- 24669535
TI  - The case of the lateral-limb lymphedema.

PMID- 24669536
TI  - Chapter program chair combines education and charitable giving for fun for all.

PMID- 24669537
TI  - Have the moral courage to do the right thing.

PMID- 24669538
TI  - Smoking and animal-based diets are leading lifestyle cancer risk factors in new
      study.

PMID- 24669539
TI  - Preface. Epidemiological studies of workplace musculoskeletal disorders.

PMID- 24669540
TI  - The NIOSH lifting equation and low-back pain, Part 1: Association with low-back
      pain in the backworks prospective cohort study.
AB  - OBJECTIVE: The aim of this study was to evaluate relationships between the
      revised NIOSH lifting equation (RNLE) and risk of low-back pain (LBP).
      BACKGROUND: The RNLE is commonly used to quantify job physical stressors to the
      low back from lifting and/or lowering of loads. There is no prospective study on
      the relationship between RNLE and LBP that includes accounting for relevant
      covariates. METHOD: A cohort of 258 incident-eligible workers from 30 diverse
      facilities was followed for up to 4.5 years. Job physical exposures were
      individually measured. Worker demographics, medical history, psychosocial
      factors, hobbies, and current LBP were obtained at baseline. The cohort was
      followed monthly to ascertain development of LBP and quarterly to determine
      changes in job physical exposure. The relationship between LBP and peak lifting
      index (PLI) and peak composite lifting index (PCLI) were tested in multivariate
      models using proportional hazards regression. RESULTS: Point and lifetime
      prevalences of LBP at baseline were 7.1% and 75.1%, respectively. During follow
      up, there were 123 incident LBP cases. Factors predicting development of LBP
      included job physical exposure (PLI and PCLI), history of LBP, psychosocial
      factors, and housework. In adjusted models, risk (hazard ratio [HR]) increased
      per-unit increase in PLI and PCLI (p = .05 and .02; maximum HR = 4.3 and 4.2,
      respectively). PLI suggested a continuous increase in risk with an increase in
      PLI, whereas the PCLI showed elevated, but somewhat reduced, risk at higher
      exposures. CONCLUSION: Job physical stressors are associated with increased risk
      of LBP. Data suggest that the PLI and PCLI are useful metrics for estimating
      exposure to job physical stressors.

PMID- 24669541
TI  - Cumulative spine loading and clinically meaningful declines in low-back function.
AB  - OBJECTIVE: The objective was to assess the role of cumulative spine loading
      measures in the development of a clinically meaningful decline in low-back
      function. BACKGROUND: Cumulative spine loading has been a suspected risk factor
      for low-back pain for many years, yet the measures that characterize risk have
      not been well delineated. METHODS: A total of 56 cumulative exposure measures
      were collected in a prospective field study of distribution center workers. An
      individual's risk for a clinically meaningful decline in low-back function (true
      cases) was explored with daily, weekly, and job tenure cumulative exposure
      measures using univariate and multivariate statistical modeling techniques. True
      noncases were individuals with no decline in low-back function. RESULTS: An
      individual's risk for a clinically meaningful decline in low-back function (true
      cases) was predicted well versus true noncases (sensitivity/specificity =
      72%/73%) using initial low-back function (p(n)), cumulative rest time, cumulative
      load exposure, job satisfaction, and worker age. CONCLUSIONS: Cumulative rest
      time was identified as an important component for predicting an individual's risk
      for a clinically meaningful decline in low-back function. APPLICATION: This
      information can be used to assess cumulative spine loading risk and may help
      establish guidelines to minimize the risk of a clinically meaningful decline in
      low-back function.

PMID- 24669542
TI  - The NIOSH lifting equation and low-back pain, Part 2: Association with seeking
      care in the backworks prospective cohort study.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between the
      revised NIOSH lifting equation (RNLE) and risk of seeking care for low-back pain
      (SC-LBP). BACKGROUND: The RNLE is commonly used to quantify low-back physical
      stressors from lifting/lowering of loads in workplaces. There is no prospective
      study on relationship between RNLE and SC-LBP. METHOD: A cohort of 258 incident
      eligible workers from 30 diverse facilities was followed for up to 4.5 years. Job
      physical exposures were individually measured. Worker demographics, medical
      history, psychosocial factors, hobbies, and current low-back pain were obtained
      at baseline. The cohort was followed monthly to ascertain SC-LBP and quarterly to
      determine changes in physical exposure. Associations between SC-LBP and both the
      peak lifting index (PLI) and peak composite lifting index (PCLI) were tested in
      multivariate models using proportional hazards regression. RESULTS: SC-LBP
      lifetime prevalence at baseline was 31.9%, and there were 24 incident cases
      during follow-up. Factors predicting SC-LBP included job physical exposure (PLI
      and PCLI), history of low-back pain, age, female gender, and lower body mass
      index. In adjusted models, risk (hazard ratio [HR]) increased per unit increase
      in PLI and PCLI (p = .03 and .02, and maximum HR = 23.0 and 21.9, respectively).
      Whereas PCLI suggested a continuous increase in risk with an increase in PCLI,
      the PLI showed elevated, though somewhat reduced, risk at higher exposures (HR =
      14.9 at PLI = 6). CONCLUSION: Job physical stressors are associated with
      increased risk of SC-LBP. Data suggest that both the PLI and PCLI are useful
      metrics for estimating exposure to job physical stressors.

PMID- 24669543
TI  - Are workers who leave a job exposed to similar physical demands as workers who
      develop clinically meaningful declines in low-back function?
AB  - OBJECTIVE: The objective is to quantify differences in physical exposures for
      those who stayed on a job (survivor) versus those who left the job (turnover).
      BACKGROUND: It has been suggested that high physical job demands lead to greater
      turnover and that turnover rates may supplement low-back disorder incidence rates
      in passive surveillance systems. METHOD: A prospective study with 811
      participants was conducted. The physical exposure of distribution center work was
      quantified using a moment monitor. A total of 68 quantitative physical exposure
      measures in three categories (load, position, and timing) were examined. Low-back
      health function was quantified using the lumbar motion monitor at baseline and 6
      month follow-up. RESULTS: There were 365 turnover employees within the 6-month
      follow-up period and 446 "survivors" who remained on the same job, of which 126
      survivors had a clinically meaningful decline in low-back functional performance
      (cases) and 320 survivors did not have a meaningful decline in low-back
      functional performance (noncases). Of the job exposure measures, 6% were
      significantly different between turnover and cases compared to 69% between
      turnover and noncases. Turnover employees had significantly greater exposure
      compared to noncases. CONCLUSION: Turnover employees had similar physical job
      exposures to workers who remained on the job and had a clinically meaningful
      decline in low-back functional performance. Thus, ergonomists and HR should be
      aware that high turnover jobs appear to have similar physical exposure as those
      jobs that put workers at risk for a decline in low-back functional performance.

PMID- 24669544
TI  - Efficacy of the revised NIOSH lifting equation to predict risk of low-back pain
      associated with manual lifting: a one-year prospective study.
AB  - OBJECTIVE: The objective was to evaluate the efficacy of the Revised National
      Institute for Occupational Safety and Health (NIOSH) lifting equation (RNLE) to
      predict risk of low-back pain (LBP). BACKGROUND: In 1993, NIOSH published the
      RNLE as a risk assessment method for LBP associated with manual lifting. To date,
      there has been little research evaluating the RNLE as a predictor of the risk of
      LBP using a prospective design. METHODS: A total of 78 healthy industrial
      workers' baseline LBP risk exposures and self-reported LBP at one-year follow-up
      were investigated. The composite lifting index (CLI), the outcome measure of the
      RNLE for analyzing multiple lifting tasks, was used as the main risk predictor.
      The risk was estimated using the mean and maximum CLI variables at baseline and
      self-reported LBP during the follow-up. Odds ratios (ORs) were calculated using a
      logistic regression analysis adjusted for covariates that included personal
      factors, physical activities outside of work, job factors, and work-related
      psychosocial characteristics. RESULTS: The one-year self-reported LBP incidence
      was 32.1%. After controlling for history of prior LBP, supervisory support, and
      job strain, the categorical mean and maximum CLI above 2 had a significant
      relationship (OR = 5.1-6.5) with self-reported LBP, as compared with the CLI
      below or equal to I. The correlation between the continuous CLI variables and LBP
      was unclear. CONCLUSIONS: The CLI > 2 threshold may be useful for predicting self
      reported LBP. Research with a larger sample size is needed to clarify the
      exposure-response relationship between the CLI and LBP.

PMID- 24669545
TI  - Low-back pain ratings for lifetime, 1-month period, and point prevalences in a
      large occupational population.
AB  - OBJECTIVE: This manuscript systematically quantifies multiple measures of low
      back pain (LBP) prevalence by pain rating in a large, multisite cohort of
      workers. BACKGROUND: Published LBP prevalence rates vary. Studies rely on one
      measure of LBP and none report prevalence stratified by pain rating. METHOD:
      Cross-sectional analyses of baseline data from a multicenter prospective cohort
      study were performed to evaluate differences in lifetime prevalence, 1-month
      period prevalence, and point prevalence of LBP. Workers were from 28 different
      employment settings in 4 diverse U.S. states. All workers completed computerized
      questionnaires and structured interviews. LBP prevalence measures were stratified
      by pain ratings. RESULTS: A total of 828 subjects had complete health data at
      baseline. Lifetime prevalence, 1-month period prevalence, and point prevalence
      for any LBP (> or = 1/10) were 63.4%, 44.0%, and 20.8% respectively. Prevalence
      of LBP decreased with increasing pain ratings. As an example, using a threshold
      of LBP > or = 3/10 pain, prevalence measures were 61.0%, 37.6%, and 16.7%
      respectively. A threshold of LBP > or = 5/10 had prevalence measures of 51.2%,
      22.9%, and 9.9% respectively. Age, systolic and diastolic blood pressure, high
      cholesterol, high blood pressure, and tobacco use were statistically
      significantly related to lifetime prevalence of LBP. CONCLUSION: Lifetime LBP
      prevalence, 1-month period prevalence, and point prevalence stratified by pain
      ratings demonstrate a wide variation of prevalence measures of LBP and self
      reported pain ratings. Higher pain rating thresholds yield lower prevalence
      measures and may impact assessments of risk factors. Differences in pain ratings
      may allow for focused surveillance within an occupational cohort.

PMID- 24669546
TI  - The Strain Index and ACGIH TLV for HAL: risk of trigger digit in the WISTAH
      prospective cohort.
AB  - OBJECTIVE: The objective of this study was to investigate the association between
      job physical exposure (JPE) and incidence of flexor tendon entrapment of the
      digits (FTED). BACKGROUND: FTED, commonly known as trigger digit, is associated
      with age, gender, and certain health disorders. Although JPE has been suggested
      as a risk factor for FTED, there are no prospective cohort studies. METHOD: A
      cohort of 516 workers was enrolled from 10 diverse manufacturing facilities and
      followed monthly for 6 years. Worker demographics, medical history, and symptoms
      of FTED were assessed. JPE was individually measured using the Strain Index (SI)
      and American Conference of Governmental Industrial Hygienists (ACGIH) threshold
      limit value for hand activity level (TLV for HAL). Changes in JPE (assessed
      quarterly) and symptoms (assessed monthly) were recorded during follow-up. FTED
      was defined as demonstrated triggering on examination. RESULTS: Point prevalence
      of FTED at baseline was 3.6%. During follow-up there were 23 incident FTED cases
      (left and/or right hands). The incident rate for first occurrence of FTED from
      enrollment was 1.38 per 100 person-years. Risk factors were JPE, age, gender,
      diabetes mellitus, carpometacarpal osteoarthrosis, and rheumatoid arthritis. In
      multivariate models, the SI showed strong association with risk of FTED when
      treated as a continuous variable and marginal association when dichotomized (SI >
      6.1). TLV for HAL showed a statistical trend of increasing risk of FTED using the
      ACGIH limits, but no association as a continuous variable. CONCLUSIONS: Both JPE
      and personal risk factors are associated with FTED development. The SI and TLV
      for HAL are useful tools for estimating JPE.

PMID- 24669547
TI  - A prospective study of musculoskeletal outcomes among manufacturing workers: I.
      Effects of physical risk factors.
AB  - OBJECTIVE: To better characterize associations between physical risk factors and
      upper-extremity musculoskeletal symptoms and disorders, a prospective
      epidemiologic study of 386 manufacturing workers was performed. BACKGROUND:
      Methodological limitations of previous studies have resulted in inconsistent
      associations. METHOD: An individual, task-based exposure assessment strategy was
      used to assess upper-extremity exertion intensity, repetition, and time-in
      posture categories. Participants recorded time spent performing daily work tasks
      on a preprinted log, which was then used to calculate time-weighted-average
      exposures across each week of follow-up. In addition, a weekly Strain Index (SI)
      risk category was assigned to each participant. Incident musculoskeletal symptoms
      and disorders were assessed weekly. Proportional hazards analyses were used to
      examine associations between exposure measures and incident hand/arm and
      neck/shoulder symptoms and disorders. RESULTS: Incident symptoms and disorders
      were common (incident hand/arm symptoms = 58/100 person-years (PY), incident
      hand/arm disorders = 19/100 PY, incident neck/shoulder symptoms = 54/100 PY,
      incident neck/shoulder disorders = 14/100 PY). Few associations between separate
      estimates of physical exposure and hand/arm and neck/shoulder outcomes were
      observed. However, associations were observed between dichotomized SI risk
      category and incident hand/arm symptoms (hazard ratio [HR] = 1.73, 95% confidence
      interval [CI] = [0.99, 3.04]) and disorders (HR = 1.93,95% CI = [0.85,4.40]).
      CONCLUSION: Evidence of associations between physical risk factors and
      musculoskeletal outcome was strongest when exposure was estimated with the SI, in
      comparison to other metrics of exposure. APPLICATION: The results of this study
      provide evidence that physical exposures in the workplace contribute to
      musculoskeletal disorder incidence. Musculoskeletal disorder prevention efforts
      should include mitigation of these occupational risk factors.

PMID- 24669548
TI  - Evaluation of alternate category structures for the Strain Index: an empirical
      analysis.
AB  - OBJECTIVE: The purpose of this study was to develop alternative Strain Index risk
      classification categories. BACKGROUND: Strain Index scores are usually
      categorized into four Strain Index "risk categories." The "original" risk
      categories were developed in the meat-packing industry and may not be fully
      applicable to other industries. METHOD: Daily Strain Index scores were estimated
      among 276 manufacturing workers participating in a cohort study of occupational
      risk factors for hand-arm musculoskeletal symptoms. Each score was categorized
      using the original method and a new method based on quartiles of Strain Index
      score values among symptomatic participants. Models examining associations
      between original Strain Index risk categories and incident hand-arm symptoms were
      compared to models examining associations between the alternative Strain Index
      risk categories and incident hand-arm symptoms. RESULTS: Compared to the
      respective referent categories, a twofold or greater increase in the risk of
      incident hand-arm symptoms was observed for the highest original Strain Index
      risk category (HR = 2.06, 95% CI = [1.08-3.92]) and for the second highest
      alternate Strain Index risk exposure category (HR = 2.21, 95% CI = [1.26-3.85]).
      Although significant associations between Strain Index risk category and incident
      hand-arm symptoms were observed for both Strain Index categorization methods,
      model fit statistics favored the alternate approach. CONCLUSION: Results from
      this study suggests that the Strain Index risk category structure may need to be
      tailored to specific populations. APPLICATION: If verified, results from this
      study provide a better way to identify hazardous manufacturing jobs and target
      them for exposure reduction.

PMID- 24669549
TI  - The impact of posture on wrist tendinosis among blue-collar workers: the San
      Francisco study.
AB  - OBJECTIVE: The objective was to evaluate the effect of wrist posture on incidence
      of wrist tendinosis in a prospective cohort of blue-collar workers. BACKGROUND:
      Previous studies have identified awkward wrist posture as a risk factor for wrist
      tendinosis, though the magnitude of the relationship is unclear. METHOD: Workers
      (N = 413) at four industries were followed for up to 28 months with
      questionnaires and physical examinations every 4 months. Individualized exposure
      assessments of wrist posture were based on video analysis to determine the wrist
      extension/flexion angle for up to four tasks. Posture measures were calculated
      while in "heavy pinch" (> 1 kg force), "heavy power grip" (> 4 kg force), and
      across "all grips." A proportional hazards model estimated the relationship
      between time-weighted average posture measures and incidence of dominant-side
      wrist tendinosis. RESULTS: In a model based on tertiles of exposure, adjusted for
      age, gender, hand force, and repetition of exertions, risk of tendinosis more
      than doubled in the highest category (HR = 2.69, 95% CI = 1.01-7.21) across all
      grips. The relative risk was highest during heavy pinch (HR = 5.03, 95% CI = 0.74
      34.05), though not statistically significant. Increased median wrist extension
      while in heavy power grip was protective (HR = 0.24, 95% CI = 0.06-0.94).
      CONCLUSION: In this study of production workers, median wrist flexion of more
      than 70, across all grips, was associated with an increased risk of tendinosis.
      The protective findings on median wrist extension during power grip deserve
      further investigation. Work tasks and tools should be designed to prevent
      sustained wrist flexion, especially during tasks involving forceful pinch.

PMID- 24669550
TI  - The association between combination of hand force and forearm posture and
      incidence of lateral epicondylitis in a working population.
AB  - OBJECTIVE: The objective of this prospective study is to investigate the exposure
      response relationships between various workplace physical exposures of force,
      repetition, and their combination assessed at an individual level with lateral
      epicondylitis (LE). BACKGROUND: Workplace upper extremity musculoskeletal
      disorders (UEMSDs) are prevalent, disabling, and expensive. LE is one of the
      major UEMSDs in active workers. METHOD: We used detailed health history,
      symptoms, and physical examination for identifying incidence and detailed
      exposure assessment to capture work tasks of each worker and to measure
      quantitative mechanical workload. We used counting process style input of
      proportional hazards regression for modeling cumulative incidence that accounts
      for changed exposure estimates during the follow-up period when respondents
      change jobs. RESULTS: The incidence rate of LE on the dominant side was 4.91 per
      100 person-years. Adjusted for age and gender, the combined effect of forearm
      pronation > or = 45 degrees for > or = 40% of time and time spent with forceful
      exertion, including any power grip (hazard ratio [HR] = 2.8, 95% confidence
      interval [CI] = [1.35-5.77]), lifting for > or = 3% of time (HR = 2.50, 95% CI =
      [1.19-5.24]), and duty cycle for forceful exertion for > or = 10% (HR = 2.25, 95%
      CI = [1.09-4.66]), were significant predictors of dominant side LE, whereas
      neither the awkward posture nor the forceful exertion alone was significant.
      Older workers with jobs requiring a high percentage of time working with force in
      combination with awkward postures of forearm were more likely to predict LE.
      CONCLUSION: This study shows the evidence of the etiologic role of strenuous
      manual tasks in the occurrence of LE.

PMID- 24669551
TI  - Using job-title-based physical exposures from O*NET in an epidemiological study
      of carpal tunnel syndrome.
AB  - OBJECTIVE: We studied associations between job-title-based measures of force and
      repetition and incident carpal tunnel syndrome (CTS). BACKGROUND: Job exposure
      matrices (JEMs) are not commonly used in studies of work-related upper-extremity
      disorders. METHOD: We enrolled newly hired workers in a prospective cohort study.
      We assigned a Standard Occupational Classification (SOC) code to each job held
      and extracted physical work exposure variables from the Occupational Information
      Network (O*NET). CTS case definition required both characteristic symptoms and
      abnormal median nerve conduction. RESULTS: Of 1,107 workers, 751 (67.8%)
      completed follow-up evaluations. A total of 31 respondents (4.4%) developed CTS
      during an average of 3.3 years of follow-up. Repetitive motion, static strength,
      and dynamic strength from the most recent job held were all significant
      predictors of CTS when included individually as physical exposures in models
      adjusting for age, gender, and BMI. Similar results were found using time
      weighted exposure across all jobs held during the study. Repetitive motion,
      static strength, and dynamic strength were correlated, precluding meaningful
      analysis of their independent effects. CONCLUSION: This study found strong
      relationships between workplace physical exposures assessed via a JEM and CTS,
      after adjusting for age, gender, and BMI. Though job-title-based exposures are
      likely to result in significant exposure misclassification, they can be useful
      for large population studies where more precise exposure data are not available.
      APPLICATION: JEMs can be used as a measure of workplace physical exposures for
      some studies of musculoskeletal disorders.

PMID- 24669552
TI  - A prospective study of musculoskeletal outcomes among manufacturing workers: II.
      Effects of psychosocial stress and work organization factors.
AB  - OBJECTIVE: The aim of this study was to characterize associations between
      psychosocial and work organizational risk factors and upper-extremity
      musculoskeletal symptoms and disorders. BACKGROUND: Methodological limitations of
      previous studies of psychosocial and work organizational risk factors and
      musculoskeletal outcomes have produced inconsistent associations. METHOD: In this
      prospective epidemiologic study of 386 workers, questionnaires to assess decision
      latitude ("control") and psychological job demands ("demand") were administered
      to study participants and were used to classify them into job strain "quadrants".
      Measures of job stress and job change were collected during each week of follow
      up. Incident hand/arm and neck/shoulder symptoms and disorders were ascertained
      weekly. Associations between exposure measures and musculoskeletal outcomes were
      estimated with proportional hazard methods. RESULTS: When compared to the low
      demand/high-control job strain referent category, large increases in risk of
      hand/arm disorders were observed for both high-demand/high-control (hazard ratio
      [HR] = 4.49, 95% confidence interval [CI] = [1.23, 16.4]) and high-demand/low
      control job strain categories (HR = 5.18,95% CI = [1.39, 19.4]). Similar
      associations were observed for hand/arm symptoms. A strong association was also
      observed between the low-demand/low-control job strain category and neck/shoulder
      disorders (HR = 6.46, 95% CI = [1.46, 28.6]). Statistically significant
      associations were also observed between weekly stress level and weekly job change
      and several musculoskeletal outcomes. CONCLUSION: Associations between
      psychosocial risk factors and work organizational factors and musculoskeletal
      outcomes were large and in the hypothesized direction. APPLICATION: Prevention of
      occupational musculoskeletal disorders may require attention to psychosocial and
      work organizational factors in addition to physical factors. Methods to control
      adverse effects of psychosocial and work organizational risk factors should be
      explored.

PMID- 24669553
TI  - Impacts of differences in epidemiological case definitions on prevalence for
      upper-extremity musculoskeletal disorders.
AB  - OBJECTIVE: The aim of this study was to systematically evaluate prevalence based
      on variations in case definitions used for epidemiological studies of
      musculoskeletal disorders (MSDs). BACKGROUND: Prior studies of MSDs have mostly
      relied on a single case definition based on questionnaires. METHOD: In a
      multicenter prospective cohort study, we systematically collected data to
      evaluate impacts of differences in case definitions of MSDs on prevalence of
      three common musculoskeletal disorders: (a) shoulder tendinosis, (b) lateral
      epicondylalgia, and (c) carpal tunnel syndrome. Production workers were from 21
      employment settings in three diverse U.S. states and performed widely varying
      work. All workers completed laptop-administered structured interviews, two
      standardized physical examinations, and nerve conduction studies (NCS). Case
      definitions included symptoms only, and symptoms plus physical examinations
      and/or NCS. RESULTS: A total of 1,227 subjects had complete health data at
      baseline. The prevalence for shoulder tendinosis is 23.0% if only glenohumeral
      pain is used for a case definition, compared with 8.0% if a combination of pain
      plus a positive supraspinatus test is used. The prevalence for lateral
      epicondylalgia varied on the basis of lateral elbow pain (12.0%), pain plus
      tenderness on palpation (9.9%), or pain plus tenderness on palpation plus
      resisted wrist or middle finger extension (3.5%). Carpal tunnel syndrome
      prevalence varied on the basis of tingling or numbness in a median nerve-served
      digit (29.9%) or tingling or numbness plus NCS abnormalities consistent with
      carpal tunnel syndrome (9.0%). CONCLUSION: Variations in epidemiological case
      definitions have major impacts on prevalence of common MSDs. Wide-ranging
      differences in prevalence may have impacts on purported risk factors that need to
      be determined.

PMID- 24669554
TI  - Provisional recommended weight limits for manual lifting during pregnancy.
AB  - OBJECTIVE: The National Institute for Occupational Safety and Health (NIOSH)
      Revised Lifting Equation (RNLE) was adapted to derive recommended weight limits
      (RWLs) for pregnant workers and to develop corresponding guidelines for
      clinicians. BACKGROUND: In the past three decades there has been a large increase
      in the number of women employed outside the home and remaining in the workforce
      during pregnancy. Practical authoritative guidelines based on accumulated
      evidence are needed to inform allowable work activity levels for healthy pregnant
      workers. METHOD: Empirically based lifting criteria established by NIOSH to
      reduce the risk of overexertion injuries in the general U.S. working population
      were evaluated for application to pregnant workers. Our evaluation included an
      extensive review of the literature linking occupational lifting to maternal and
      fetal health. Decision logic and supporting literature are presented, along with
      computational details. RESULTS: Provisional RWLs for pregnant workers were
      derived from the RNLE, along with guidelines for clinicians. The guidelines
      advise against pregnant workers lifting below midshin and overhead. CONCLUSION:
      Based on our review of the available evidence, we present lifting thresholds that
      most pregnant workers with uncomplicated pregnancies should be able to perform
      without increased risk of adverse maternal and fetal health consequences. Except
      for restrictions involving lifting from the floor and overhead, the provisional
      guidelines presented are compatible with NIOSH lifting recommendations adopted in
      the early 1990s for the general working population. APPLICATION: Implementation
      of these provisional guidelines could protect millions of female workers in the
      workplace from fetal and maternal lifting-related health problems.

PMID- 24669555
TI  - Musculoskeletal pain and reported workplace assault: a prospective study of
      clinical staff in nursing homes.
AB  - OBJECTIVE: This study examined prospectively the effect of workplace violence on
      musculoskeletal symptoms among nursing home workers. BACKGROUND: Previously we
      reported a cross-sectional relationship between physical assaults at work and
      musculoskeletal pain. This follow-up provides stronger evidence of the effect of
      workplace violence on musculoskeletal outcomes within the same workforce over two
      years. METHOD: Nursing home workers who responded to three consecutive annual
      surveys formed the study cohort (n = 344). The outcomes were any musculoskeletal
      pain, widespread pain, pain intensity, pain interference with work and sleep, and
      co-occurring pain with depression. The main predictor was self-reported physical
      assault at work during the 3 months preceding each survey. Prevalence ratios
      (PRs) were assessed with log-binomial regression, adjusting for other workplace
      and individual factors. RESULTS: Every fourth nursing home worker, and 34% of
      nursing aides, reported persistent workplace assault over the 2 years. Among
      respondents assaulted frequently, two thirds experienced moderate to extreme
      musculoskeletal pain, and more than 50% had pain interfering with work and/or
      sleep. Baseline exposure to assault predicted pain outcomes 1 year later.
      Repeated exposure was associated with a linear increase over 2 years in the risks
      of pain intensity, interference with work, and interference with sleep; co
      occurring pain and depression had an adjusted PR of 3.6 (95% CI = 1.7-7.9).
      CONCLUSION: Workplace assault, especially when repeated over time, increases the
      risk of pain that may jeopardize workers' ability to remain employed.
      APPLICATION: More effective assault prevention would protect and support the
      workforce needed to care for our increasing elderly and disabled population.

PMID- 24669556
TI  - Reference values for physical performance measures in the aging working
      population.
AB  - OBJECTIVE: The aim of this study was to determine reference physical performance
      values in older aging workers. BACKGROUND: Cross-sectional physical performance
      measures were collected for 736 manufacturing workers to assess effects of work
      and nonwork factors on age-related changes in musculoskeletal function and
      health. METHOD: Participants underwent surveys and physical testing that included
      bioelectrical impedance analysis, range-of-motion measures, exercise testing, and
      dynamic assessment. RESULTS: Physical characteristics, such as blood pressure and
      body fat percentage, were comparable to published values. Dynamic and range-of
      motion measurements differed from published normative results. Women had age
      related decreases in cervical extension and lateral rotation. Older men had
      better spinal flexion than expected. Predicted age-related decline in lower
      extremity strength and shoulder strength in women was not seen. Men declined in
      handgrip, lower-extremity strength, and knee extension strength, but not trunk
      strength, across age groups. There was no appreciable decline in muscle fatigue
      at the trunk, shoulder, and knee with aging for either gender, except for the
      youngest age group of women. CONCLUSION: Normative values may underestimate
      physical performance in "healthy" older workers, thereby underappreciating
      declines in less healthy older workers. Work may be preservative of function for
      a large group of selected individuals. A "healthy worker effect" may be greater
      for musculoskeletal disease and function than for heart disease and mortality.
      APPLICATION: Clinicians and researchers studying musculoskeletal function in
      older workers can use a more specific set of reference values.

PMID- 24669557
TI  - [50 years of total hip prosthesis--a tribute to Prof. Sir John Charnley].
AB  - November 2012 marked the 50th anniversary of the first implantation of a
      successful and long-lived hip endoprosthesis, which was performed by Prof Sir
      John Charnley in the "Centre for Hip Surgery" at a small country place in the
      north-west England. John Charnley (1911-1982) finished medical school at the
      Victoria University of Manchester in 1935, and than started training in
      orthopaedics at the Manchester Royal Infirmary, and completed it after the Second
      World War, in which he served as a volunteer. After that he continued working in
      the same hospital, and, apart from that he worked as a lecturer at the University
      of Manchester, and from 1949 as a visiting surgeon in the Wrightington Hospital.
      In 1958 Charnley decided to put his efforts into the development of hip
      replacement research and surgery, and initiated the foundation of the "Centre for
      Hip Surgery" with Biomechanical laboratory in the Wrightington Hospital in 1960,
      where the intesive basic and clinical research started, and becuase of that
      Charnley in 1962 left Manchester and moved with a full time practice at the
      Wrightington Hospital. That period of research time was not easy, there were many
      "trial and tribulations", but, owing to the tenacity and inventive mind of
      Charnley, in 1962 a new prosthesis consisting of a cemented metal stem with a 22
      mm head articulating with a cemented polyethilene acetabular component, and with
      a low frictional torque was designed. The first such prosthesis, which later
      produced excellent long-term results, was implanted on November 22nd, 1962, and
      today, when we look back over a distance of fifty years, we can conclude that
      that day could be considered as a beginning of a modem aloarthroplastic surgery,
      and certainly as one of the greatest orthopaedic advance in the whole of the 20th
      century; and all that was initiated and promoted by Prof. Sir John Charnley.

PMID- 24669558
TI  - Holmium laser enucleation versus transurethral resection of the prostate: a
      comparison of clinical results.
AB  - Holmium laser enucleation of the prostate (HoLEP) represents a great potential
      alternative technique to standard transurethral resection of the prostate (TURP).
      We present 12-month follow up results of a randomized clinical trial, comparing
      HoLEP with TURP. A total of 40 patients with BPH and prostate volume < 50 g, have
      been randomized for HoLEP (n = 20) or TURP (n = 20). Urinary tract ultrasound
      with postvoid residual urine (PVR), International Prostate Symptom Score (IPSS)
      and Single Question Quality of Life (QoL) Score were evaluated preoperatively and
      during the follow-up period at 1, 3, 6, and 12 mo postoperatively. Intra- and
      perioperative data as well as early and late complications were assessed.
      Operative time was longer in the HoLEP group (p < 0.001); catheterisation time (p
      < 0.05) and hospital stay (p < 0.05) shorter. Hemoglobin levels drop (p < 0.001)
      was higher in the TURp group. Early and late postoperative complications were
      more frequent in the TURp group (p < 0.001). Follow-up data favored the HoLEP
      group, both regarding IPSS at 6-month (p < 0.05) and 12-month (p < 0.01), and
      single question QoL score, at 6-month (p < 0.01) and 12-month (p < 0.05). PVR was
      lower in the HoLEP group at 6-month (p < 0.01). HoLEP demonstrates superiority to
      TURp in regards to perioperative parameters and follow-up data and has a great
      potential to become the new gold standard in the surgical treatment of BPH.

PMID- 24669559
TI  - Current treatment options of acquired flatfoot.
AB  - Symptomatic acquired flatfoot is an important orthopaedic problem, due to
      progressive loss of whole foot function and the increasing problem of patient
      disability. It is a complex entity, involving the tibialis posterior tendon,
      ankle joint, hindfoot and midfoot. In most cases the posterior tibial tendon
      (PTT) is the root cause of acquired flat foot, but there are other contributors
      and many different factors have an influence. The clinical picture varies
      depending on the stage of the deformity, as well as the treatment approach.
      Initially soft tissue procedures, synoviectomy and augmentation of the PTT are
      advised. In stage 2, lateral column lengthening and calcaneal osteotomy, with
      soft tissue - tendon transfers (TA, FHL, FDL) are recommended. In stage 3
      subtalar, double or triplearthodesis is preferable, while in stage 4 pantalar
      fusion is indicated. This article elaborates on the etiology, the clinical
      picture, diagnosis and treatment modalities.

PMID- 24669561
TI  - [Neuroendocrine tumors of gastrointestinal tract: the paradigm that lasts].
AB  - Historically, the tumors that were morphologically different and clinically less
      agressive than the more common gastrointestinal adenocarcinomas were clasified
      under carcinoid tumors. However, the development of molecular biology tehniques
      revealed the heterogeneity of these tumors on cellular and subcellular level and
      ther different biological behaviour. Neuroendocrine tumors of gastrointestinal
      tract originated from neuroendocrine cells scaterred across the gastrointestinal
      mucosa. As a result these tumors were capable of secreting many different
      neurotransmiters, which may or may not be biologically active. The incidence of
      gastrointestinal NETs has been incresing over the last 2 to 3 decades. Patients
      often presented with vague, nonspecific symptoms which resulted in delayed
      diagnosis and adequate treatment. In this article, we discuss the nature of
      gastrointestinal NETs, clinical presentation, treatment options and prognosis.

PMID- 24669560
TI  - Clinical experience in treatment of thrombotic thrombocytopenic purpura-
      hemolytic uremic syndrome with 28 patients.
AB  - BACKGROUND: Neither optimal treatment nor significance of ADAMTS13 (A Desintegrin
      And Metalloprotease with ThromboSpondin type 1 repeats) activity for diagnosis
      and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic
      syndrome (HUS) have not been defined yet. The aim of the report is to analyze
      response to different volumes of plasma exchange (PE), and relationship to
      ADAMTS13. DESIGN AND METHODS: 28 patients clinically diagnosed with idiopathic
      TTP (n = 18), secondary TTP (n = 4), atypical HUS (n = 3) and typical HUS (n = 3)
      manifested 31 acute episodes. Patients were treated with PE in 26, and with
      plasma transfusion in 5 episodes with additional different therapies. RESULTS: PE
      volumes were as follows: 1 in 7, 1.5 in 3, 2 in 14, and intensifying schedule (1
      to 1.5) in 2 episodes. Procedure number was lower in patients treated with 2 and
      1.5 (p = 0.019) than in those treated with 1 volume exchange and PE intensifying,
      respectively (p = 0.010). PE response rate was 25/26 (96.15%). Exacerbation
      frequency was higher in idiopathic TTP patients (3/19) treated with 1 compared
      with patients treated with > 1 volume exchange (p = 0.003). Survival rate was
      25/28 (89.29%). ADAMTS13 activity was reduced in 22 with severe deficiency in 14
      patients. CONCLUSION: Patients responded to different treatments regardless of
      ADAMTS13 activity, requiring less PEs with larger volume exchanges.

PMID- 24669562
TI  - How much do we pay for caesarean section--a pilot study in Serbia.
AB  - BACKGROUND: Different types of labour need different resources. Subsequently,
      different costs should be expected. AIM: The aim of the study was to determine
      costs of planned Caesarean section (C-section) in relation to costs of
      spontaneous (SVD) and induced vaginal (IVD) delivery. METHODS: Retrospective
      study was conducted for the period January 1st-December 31st, 2010. Database of
      Health Insurance Fund of Republic of Serbia was used as a data source. Direct
      medical costs of labor were estimated for mother/newborn pair. RESULTS: The
      sample was consisted of 99 women where 46.5% had SVD, 28.3% IVD and 25.2% C
      section. The average costs of labor, regardless of method, were 417.02+284.14
      EUR. Costs of C-section were higher compare to SVD (640.18 +/- 240.04 vs. 243.27
      +/- 131.70 EUR, p < 0.05) and IVD (640.18 +/- 240.04 vs. 497.10 +/- 327.91 EUR, p
      < 0.05). CONCLUSION: Considering high costs of C-section, it is necessary to
      review such clinical practice for the purpose of optimizing the use of resources.

PMID- 24669563
TI  - [Degree of renal insufficiency in patients undergoing ileal conduit as a form of
      urinary diversion in relation to the type of ureteral insertion].
AB  - Ileal conduit as a form supravesical derivaton, is still one of most popular
      method of urinary diversion, in daily urological practice. Bearing in mind this
      fact, this type of diversion, rightfully so, is also called the "gold standard"
      in the derivation of urine. Considering the fact of unnatural route of
      elimination of urine from the upper urinary tract that occurs during creation of
      ileal conduit, it is reasonable to expect that, in time, this type of diversion
      lead to some degree of renal insufficiency. Some authors, this effect on renal
      function, attribute to specific type of ureterointestinal anastomosis during
      formation of ileal conduit. A very important part of the surgical technique of
      creating ileal conduit is precisely a step of implantation ureters into the
      intestinal segment. The ultimate goal is to enable a more natural way of
      evacuation of urine from the upper urinary tract in terms of maintaining the
      quality of renal function. Numerous authors describes a quite number of
      techniques of ureteral implantation into the intestinal segment (Wallace A,
      Wallace B, Nesbit-Bricker, Le Duc ...). Each of these techniques has its own
      strengths and weaknesses, and the decision witch technique will be applied is
      still in the hand of urologist--operator, individually.Bearing in mind the fact
      of unnatural route of elimination of urine from the upper urinary tract that
      occurs during creation of ileal conduit, it is reasonable to expect that the
      renal function over the time will start to show signs of incipient or advanced
      failure. OBJECTIVE: To determine the most appropriate type ureterointestinal
      anastomosis in forming ileal conduit, as a form of supravesical urinary
      diversion, to ensure adequate renal function postoperatively as an important
      parameter of quality of life. METHODS AND PATIENTS: This is a retrospective
      study, which covered a population of 193 patients treated at the Department of
      Urology, Clinical Center of Serbia, who underwent creation of ileal conduit as a
      form of urinary diversion. The study was conducted 2007-2011. Postoperative
      follow-up lasts up to 48 months. The assess of the level of renal insufficiency
      were analyzed by monitoring parameters which determine the degree of anemia, and
      biochemical parameters of renal function. We have investigated three techniques
      of insertion of the ureters into the ileal conduit, which are used in the daily
      practice (Wallace A, Wallace B, Nesbit-Bricker). CONCLUSION: Kidney failure
      occurs equally often in all patients who underwent urinary diversion by ileal
      conduit, ignoring the type of insertion of the ureters to the intestinal segment.

PMID- 24669564
TI  - The impact of postoperative pain on early ambulation after hip fracture.
AB  - Hip fractures are the most serious consequence of falling in older people with
      osteoporosis. Early ambulation is one of the main goals of inpatient
      rehabilitation aimed at reducing negative effects of immobilization, and
      promoting functional recovery. Recognizing the role of different factors that are
      associated with time to ambulation time after hip fracture surgery may help
      decrease morbidity and mortality rates. The aim of this study was to examine the
      impact of postoperative pain time to ambulation following hip fracture surgery. A
      total of 96 patients who consecutively presented at the Clinic for Orthopaedic
      Surgery and Traumatology, Clinical Center Serbia during a 6 month period were
      included in the study. Subjects were assessed regarding socioedemographic
      characteristics, prefracture functional status, cognitive status, general health
      status, fracture type, type of anaesthesia, and waiting time for surgery. The VAS
      scale (0-100) was used to measure pain intensity on the first postoperative day.
      Our results revealed that patients, whose time to ambulation was = 48 h
      postoperatively were of worse physical health, and had significantly higher VAS
      score on the first postoperative day. Unrelieved pain in geriatric hip fracture
      patients is associated with delayed ambulation. Future research should confirm
      the posi-tive effects of aggressive pain management programs on early functional
      outcome in elderly patients who sustain hip fractures.

PMID- 24669565
TI  - [The effect of neoplastic disease and systemic disease of connective tissue on
      the occurrence of dehiscence laparotomy].
AB  - Dehiscence after laparotomy is one of the major complications of laparotomy. This
      is a partial or complete wound with disruption and evisceratio abdominal organs
      and require urgent reintervention. The aim of this study was to determine the
      impact of neoplastic disease and systemic disease of connective tissue on the
      occurrence of dehiscence laparotomy. A prospective study were included 612
      patients operated at the Clinic for General Surgery in Nis in the period from
      January 2009 to December 2010. The effect of neoplastic disease and the presence
      of systemic disease of connective tissue on the occurrence of dehiscence
      laparotomy. Results are displayed numerically and in percentages. Of the total 24
      patients with dehiscence laparotomy, 15 patients were male or 62.5% and 9 female
      patients, or 37.5%. There was a statistically significant association between
      dehiscence laparotomy and neoplastic diseases (c2 = 42,196; p < 0.01). There was
      no statistically significant association between dehiscence laparo-tomy and
      systemic disease of connective tissue (c2 = 0,028; p > 0.05). In patients with
      neoplastic diseases dehis-cence laparotomy is common, and in patients suffering
      from systemic disease of connective tissue dehiscence laparotomy occurs less
      frequently.

PMID- 24669566
TI  - How to treat complex regional pain syndrome in rehabilitation settings?
AB  - Complex regional pain syndrome is chronic neuropatic pain condition which usually
      arise after trauma. It is associated with some of the sensory, vasomotor,
      sudomotor, motor and trophic symptoms and sings. Due to variability of symptoms
      and long-lasting pain, these patients are hard to rehabilitate. They exhibit
      activity related fear and so have pronounced functional limitations. Adequate
      rehabilitation procedures, frequently long lasting, are essential for their
      optimal recovery, so rehabilitation specialist should constantly update their
      knowledge on this issue. Emerging researches on pathophysiology, diagnosis and
      treatment of CRPS created a need for systematization of current body of evidence.
      Available researches on efficacy of different treatment options are still
      insufficient to create precise therapy guidelines, so future researches are
      needed in order to promote better rehabilitation outcomes.

PMID- 24669567
TI  - [Clinical-epidemiologic characteristics of large, invasive basal cell carcinomas
      of the scalp].
AB  - We studied a large, invasive basal cell carcinoma of the scalp in 42 operated
      patients (53 tumors) of which 26 patients with recurrent and 16 with no
      recurrence. This is a rare clinical form of this tumor that invades the skin in
      addition to some or all of the following structure: soft tissue scalp, skull,
      brain and brain membranes. The literature is known as the Giant basal cell
      carcinoma according to TNM classification of BCC in pT4 stage. Caused by
      aggressive subtypes of BCC. Treatment is surgical and involves only large,
      mutilate surgery and extensive reconstruction. Relapse often occurs. The aim was
      to analyze clinical and epidemiological characteristics of large, invasive basal
      cell carcinoma of the scalp, finding the causes of relapse and proposal timely
      diagnosis. We have concluded that the appearance of tumors in the frontal and
      pariental region of the scalp is related to the presence of known risk factors,
      that tumors often penetrate bones and brains resulting in more frequent
      recurrence in this localization. All tumors were caused by aggressive forms of
      BCC. Patients in the group with recurrent, previously responded to treatment and
      had more surgery than patients without recurrence. Treatment-related adverse
      events occurred in most patients (recurrence and/or death).

PMID- 24669568
TI  - [Aspirin withdrawal in high risk cardiac patients before the operation of total
      colectomy with resection of ileum--case report].
AB  - Coronary artery disease is one of the risk factors for myocardial infarction and
      it is present in 40% of patients who are undergoing noncardiac surgery. Despite
      evidence of the benefit of the antiplatelet therapy in patients at risk of
      cardiac complications, aspirin treatment is often discontinued before surgery due
      to the risk of perioperative bleeding. In many studies and meta-analysis it is
      shown that aspirin withdrawal in perioperative period was associated with three
      fold higher risk of major adverse cardiac events. Perioperative continuation of
      aspirin increase the rate of bleeding by 1.5, but it doesn't increase the level
      of the severity of bleeding complications. In perioperative periode aspirin is
      discontinued only if it is estimated that the bleeding risk is higher than the
      risk of thrombosis. In the paper authors present a case report of patient who
      developed a perioperative myocardial in-farction as a consequence of aspirin
      withdrawal before total colectomy.

PMID- 24669569
TI  - Unusual presentation of a huge hematoma in the liver derived from a
      nasopharyngeal carcinoma.
AB  - INTRODUCTION: Nasopharyngeal carcinoma (NPC) has the propensity to develop
      distant metastases at a high rate and with poor prognosis. The metastatic sites
      are usually multifocal and involve the bones, lungs, liver and distant lymph
      nodes. The management of metastatic disease is essenti- ally palliative and is
      based on radiochemotherapy. METHODS: A 50-year old man with a huge hematoma in
      the liver derived from a diagnosed NPC was treated with intermittent drainage of
      the hepatic hematoma for abdominal decompression, and the cavity was packed with
      omentum. In addition, 2 suspected metastatic lesions were excised. Neoadjuvant
      radiochemotherapy followed by concurrent chemotherapy was administered. RESULTS:
      After surgical treatment of the huge hematoma, the suspect sites in the liver
      were diagnosed as metastatic carcinoma, similar to the primary tumor. Several
      months later, bone metastatic lesions in the vertebra and oss iliaca dextra were
      detected due to distant metastasis. CONCLUSION: Treatment of metastatic NPC is
      essentially palliative and survival is usually poor.

PMID- 24669570
TI  - The case of the diverticular bladder tumor treated with diverticulectomy.
AB  - INTRODUCTION: The majority of diverticular bladder tumors (DBT) are urothelial.
      Due to the lack of the muscular layer in the diverticulum, the progression of
      these tumors is easier than in the bladder wall. CASE REPORT: The case of
      invasive DBT with painless hematuria is presented. The patient was treated with
      diverticulectomy. CONCLUSION: Unifocal Stage-T3 DBTs can be successfully treated
      with diverticulectomy.

PMID- 24669571
TI  - [Small cell neuroendocrine carcinoma of the urinary bladder].
AB  - Among neuroendocrine tumors of the urinary bladder, small cell carcinoma (SCCB)
      is the most common one. Less frequent is carcinoid tumour and very rare is a
      large-cell neuroendocrine carcinoma. Small cell neuroendocrine carcinoma is a
      very aggressive tumour, with major frequency in the seventh decade. In 95% of
      patients it presents with hematuria and muscle invasive disease. A case of a
      patient with the urinary bladder tumour, which had muscle invasion and extension
      in perivesical tissue, was presented. The patient was diagnosed with combined
      form of the tumour, consisting of small cell and squamous cell patterns. Some of
      the imunochistochemical markers used in diagnosis were chromogranin A,
      synaptophysin, cytokeratins, LCA and Ki-67. Consequently, neuroendocrine
      differentiation of small cell patterns of the tumour was proven. Neoadjuvant
      cisplatin- based chemotherapy followed by radical resection should be considered
      as the treatment of choice in surgically resectabile SCCB. Because of that it is
      essential to make histopathologic diagnosis of SCCB in transuretral tumour
      samples using, chromogranin A or synapthysin.

PMID- 24669572
TI  - Complications during cesarean delivery in a patient with two previous
      myomectomies.
AB  - INTRODUCTION: Myomas are associted with numerous pregnancy-related maternal and
      fetal complications, including high rate of cesarean deliveries. CASE OUTLINE: We
      present a woman with huge posterior myoma who had two previous myomectomies.
      During the cesarean section, the anatomy was found to be grossly distorted. Thus
      it was necessary to make an inverted T-incision on the uterus, which facilitated
      delivery of the fetus. The patients postoperative recovery was uneventful.
      CONCLUSION: This case illustrates the difficulties that may arise during cesarean
      section in the presence of uterine myomas in women with previous myomectomies.
      Clinicians should be prepared to manage those difficulties with inverted T
      incision in order to prevent fetal injuries. Such operations should be performed
      by an experienced obstetrician.

PMID- 24669573
TI  - Predictive importance of index of asymmetry in recovery following stroke.
AB  - Quantitative electroencephalography (QEEG) has been proved as a powerfully tool
      for prediction of the stage of residual functional disable. For predictive value
      of QEEG, individual profile of every patient is most important. It has been
      demonstrated that Index of brain symmetry (BSI) present specific asymmetry of
      power spectra between two brain hemispheres and it has been normalized from 0
      (perfect symmetry) and 1 (maximal asymmetry). METHOD: We included in our analysis
      86 normal subjects in EEG recording. We did frequency analysis using Fast Fourier
      transformation (FFT) in power spectra for 16 derivations and 20 frequency bands,
      from 0 to 20Hz, with step of 1. On the base of that data, we got normal
      distribution with coefficient of variation less than 30%. We determined grades of
      frontier of allowance in all derivations and in all frequency bands, in the
      conditions with closed eyes and with eyes open in normal control. Maximal grade
      for each condition was 320. In this way we appointed the standard. We recorded
      the EEG in patient on admission and after two months of neurorehabilitation. We
      did the same procedure in every patients and on the base of the standard we
      calculated grades. On the base of calculated grades, we determine index of
      asymmetry using formula (l-d)/(l+d) x 100, and make the curves. Curvilinear of
      this curve and extent of its declination from 0 suggest on electrophysiological
      stage of brain. RESULTS: Index of asymmetry in patients with poor long-lasting
      recovery is more, equal and little bit smaller on control, after two months of
      rehabilitation in relation to first EEG recording on admission. On the other hand
      in patients with good long-lasting recovery. Index of assymmetry is reduced.

PMID- 24669574
TI  - Emil Theodor Kocher (1841-1917)--orthopaedic surgeon and the first surgeon Nobel
      Prize winner.
AB  - Theodor Emil Kocher (1841-1917), born in Bern, educated in many universities in
      Europe. Kocher as many surgeons of that time performed orthopedic surgery,
      general surgery, neurosurgery and endocrine surgery, but he become famous in
      orthopaedic surgery and endocrine surgery. He is remember as a surgeon who
      described the approach to the hip joint, elbow joint, maneuver for the reduction
      of dislocated shoulder joint. He introduced many instruments and many of them,
      such as Kocher clamp is still in use. Most important Kocher work was the thyroid
      gland surgery, and he received the Nobel Prize for Medicine in 1909, for-in this
      matter. His nature of meticulous surgeon, scientific and hard working person,
      dedicated to his patients and students made- found him the place in a history of
      medicine.

PMID- 24669575
TI  - [Carcinoid syndrome in neuroendocrine tumors--not easy to recognize].
AB  - Neuroendocrine tumors (NET) are solid potentially malignant tumors originated
      from the diffuse neuroendocrine system. They could origin in many organs, with
      highest prevalence in lungs, small intestine and rectum. Characteristics of NET
      are slow growth, non-specific clinical presentation causing diagnostic problems.
      Thus, in majority of patients diagnosis is established in the metastatic phase of
      the disease. Hopefully, there are new and very potent treatment options capable
      to successfully control the disease. Clinical presentation cause local tumor
      growth or para-neoplastic syndrome. Secretory active tumors produce peptides or
      hormones causing different clinical syndromes. In most cases NET cause carcinoid
      syndrome. It is often misinterpreted, because similar symptoms are present in
      more prevalent disorders. Symptoms are not specific and include flashing,
      diarrhea, abdominal pain, right heart disease, bronchoconstriction ... and to
      establish the right diagnosis medical doctor have to think about NET as a
      possibility. Thus, it is very important to recognize symptoms and signs of the
      carcinoid syndrome, and distinguish them from other gastrointestinal disorders.
      Early diagnosis and treatment have significant impact in control of the disease,
      and overall treatment results.

PMID- 24669576
TI  - [Degree of postoperative renal deterioration in patients who have undergone ileal
      conduit as a form of urinary diversion in relation to the type of insertion of
      the ureter].
AB  - Substitution of the bladder with segment of the digestive tract, within the
      radical treatment of bladder cancer, as well as treatment of the other bladder
      abnormality, is extremely demanding surgical procedure, that aims adequate
      treatment of the underlying disease and provide patient's renal function within
      physiological level. Surgical implantation of the ureter into the intestinal
      segment are an important part of the surgical technique, the formation of ileal
      conduit, with the ultimate aim of providing a more natural way of evacuation of
      urine from the upper urinary tract in terms of maintaining the adequate quality
      of renal function. Which of the existing surgical method of implantation of
      ureter in the intestinal segment will be applied, it is for urologist to decided,
      according to his affinity and/or his operating school of origin. The literature
      describes many procedures of this technique (Wallace A, B Wallace, Nesbit
      Bricker, Le Duc). Bearing in mind that the ileal conduit, as a form of
      supravesical derivation, is still one of most widely used method of urinary
      diversion, with a very large number of patients during the follow-up period were
      recorded certain complications of renal function disorders, which by some authors
      attributed to a type of ureterointestinal anastomoses, during the creation of
      ileal conduit. Having in mind the fact of unnatural route of elimination of urine
      from the upper urinary tract that occurs during creation of ileal conduit, it is
      reasonable to expect some degree of renal deterioration. These complications
      require prompt resolution. Bearing in mind the fact of unnatural route of
      elimination of urine from the upper urinary tract that occurs during creation of
      ileal conduit, it is reasonable to expect that the renal function over the time
      will start to show signs of incipient or advanced failure. OBJECTIVE: The main
      objective is to show the degree of renal deterioration, postoperatively,
      according to the type of insertion of the ureters to the ileal conduit. METHODS
      AND PATIENTS: The study was conducted retrospectively on material of Urological
      Clinic, Clinical Center of Serbia and on material of Faculty of Medicine,
      University of Belgrade, on 193 patients, for a period of five years (2007 to
      2011), with a time of postoperative follow-up of patients up to 48 months (four
      years). Assessment of the level of renal deteriorisation was performed by
      ultrasound examination during regular audits of patients during follow-up.
      CONCLUSION: It was found that all three examed techniques in an insertion of
      ureter into ileal conduit were equally satisfactorily, with the similar degree of
      postoperative complications. Based on these facts, we can conclude, that the
      quality of life of patients in all three analyzed groups of ureteral insertion in
      the ileal conduit, approximately the same.

PMID- 24669577
TI  - Ultrasonographic evaluation of visceral and subcutaneous abdominal fat tissue
      before and after bariatric surgery.
AB  - Visceral fat is considered a key factor in the development of metabolic syndrome
      and other pathological conditions and diseases associated with obesity.
      Therefore, analysis of the dynamics of reducing the amount of abdominal visceral
      fat is important for evaluating the therapeutic effects of different modalities
      of obesity treatment, including bariatric surgery. In 53 obese patients visceral
      and subcutaneous abdominal adipose tissue was measured by ultrasonography (US)
      before and after bariatric surgery, in the period of 1, 3, 6 months. At the same
      time, standard anthropometric parameters were assessed: body mass (m), BMI, waist
      circumference (WC), and hip circumference (HC). Five diameters of the visceral
      abdominal fat (VAF) were measured: IAFT (Intraabdominal Fat Thickness), LV
      (Lienal Vein), VF (Visceral Fat), MES sum (Mesenterial leafs) and Max PFT
      (Maximal Preperitoneal Fat Thickness), and three diameters of the subcutaneous
      abdominal adipose tissue (SCAF): Min SFT (Minimal Subcutaneous Fat), and MaxSFTa
      and MaxSFTb (Maximal Subcutaneous Fat Thickness a and b). Statistically
      significant decrease in all anthropometric parameters, except HC was registered
      1, 3 and 6 months after the surgery. We registered the decline of almost all US
      diameters of abdominal adipose tissue in the follow-up period, but statistically
      significant decrease were found only in the diameters of visceral adipose tissue:
      IAFT after 1 and 3 months (p = 0.031 and p = 0.027); VF after 1 month (p =
      0.031), LV after 6 months (p = 0.011), and MESsum after 3 and 6 months (p = 0.001
      and p = 0.028), as well as MaxSFTb, at 1 month follow-up (p = 0.015). In the
      short-term follow-up period after the bariatric surgery, there was a significant
      decrease in body mass, BMI and WC, and ultrasonography revealed a significant
      reduction in the diameters of the visceral abdominal fat.

PMID- 24669578
TI  - Comparison of Z-plasty, limberg flap, and asymmetric modified Limberg flap
      techniques for the pilonidal sinus treatment: review of literature.
AB  - BACKGROUND AND AIMS: The aim of this study is to analyze and compare the early
      complications and recurrent results of Z-plasty, Limberg flap, and asymmetric
      modified Limberg flap both demographically and clinically. MATERIALS AND METHODS:
      Between March 2009 and February 2010, a total of 45 patients with pilonidal sinus
      were enrolled in this study. 10 of 45 patients (22.2%) required Z-plasty; 24
      patients (53.3%) had surgery with Limberg flap closure, and 11 patients (24.4%)
      had asymmetric modified Limberg flap. RESULTS: A total of 45 patients were
      included in the study (mean age: 23.36 > +/- 3.4 (range, 20-33) years). When we
      compared duration of operation and the length of stay in hospital, no
      statistically significant findings were detected (p = 0.595 and p = 0.23,
      respectively). The mean follow-up was 22.4 (range, 18-24) months. Recurrence was
      not seen in any of the patients. CONCLUSIONS: Our results were similar: the
      comparison of the three techniques revealed no significant differences regarding
      early complications and recurrence.

PMID- 24669579
TI  - Routine chest radiographs in the surgical intensive care unit: can we change
      clinical habits with no proven benefit?
AB  - Daily routine chest radiographs (CR) are commonly performed in surgical ICU.
      Unnecessary CR increase costs and expose the staff and the patients to radiation
      risk. The goal of our study was to estimate the value of daily routine CR in the
      ICU and to determine the correlation between CR and physical findings in surgical
      ICU patients. Prospective observational study was conducted during period of two
      months at the ICU department at the Clinic for Digestive Surgery, Clinical Center
      of Serbia, Belgrade. It included 97 consecutive patients who underwent digestive
      surgery and stayed at the ICU for at least two days. During their ICU stay, CRs
      were obtained as a clinical routine or to monitor lung pathology. Patients were
      followed daily, and CRs (as the proportion of positive findings) were compared
      with physical examination and clinical presentation. A total of 717 CRs were
      obtained, median number per patient was 4.0 (2.0-7.0). Proportion of positive
      findings was significantly higher comparing to auscultation until the sixth day
      of ICU stay. There was no difference in CR findings from day to day after the
      sixth day. Therapeutic efficacy of CRs was low as only 56 (7.8%) resulted in a
      change of patient management. We conclude that daily routine CRs are justified in
      the first six days of ICU stay, and after that time they show no advantages over
      clinical examination.

PMID- 24669580
TI  - EEG study of visual reactivity in aphasic patients.
AB  - AIM: To compare patients with good and poor recovery after 1 and 3 months from
      onset of poststroke aphasia and to correlate the quality of recovery with
      quantitative EEG (QEEG) measures (frequency analysis with the limits of
      variability, and index of asymmetry). METHODS: The investigation was performed on
      the sample of 32 patients with poststroke aphasia, 15 females (46.88%) and 17
      males (53.12%), mean age +/- standard deviation (SD) being 50.65 +/- 9.93 years.
      QEEG measures of this sample were compared with those in a group of 86 healthy
      controls, 39 (45.35%) females and 47 (54.65%) males, mean age +/- SD being 51.08
      +/- 10.08 years. Frequency analysis was performed in eyes closed and eyes open
      conditions in both controls and in aphasics who were tested just before and two
      month after rehabilitative treatment with speech therapy. RESULTS: We have got
      normal distribution for all derivations and all frequency bands in the group of
      healthy subjects. On the basis of this finding, we determined coefficients of
      variation in patients with poststroke aphasia and discovered that their maximal
      variability scores were significantly decreased. Compared to healthy subjects,
      the index of asymmetry between two hemispheres and between main brain regions was
      significantly higher in the aphasic patients than in controls. However, the
      differences in the index of asymmetry and limits of variability significantly
      decreased after two month treatment in the subgroup of patients with good
      improvement compared with the subgroup of patients with poor improvement of
      poststroke aphasia. CONCLUSION: QEEG measures may have predicitive value in post
      stroke aphasia.

PMID- 24669581
TI  - [Operative vs. non-operative treatment of acute Achilles tendon rupture].
AB  - INTRODUCTION: It affects most frequently middle aged recreational male sportsmen
      (30-50 years old), previously followed by prodromal symptoms (5-33%). Rupture
      spot is 3 to 5 cm above heel bone vertex (90-95%) Retrospective study. WORKING
      OBJECTIVE: Comparison of functional re-. suits and complications of cast
      immobilization non-operative treatment and open suture surgical treatment.
      MATERIAL AND METHODS: Overall 46 patients included who were treated at the Clinic
      for Orthopedics and Traumatology within the Clinical Center of Montenegro in
      Podgorica between 2004 and 2012. Patients were divided into two groups: I group
      consisted of 21 patients (45.65%) who were treated by cast immobilization and the
      II (control) group consisted of 25 patients (54.35%) who were treated by open
      surgical technique. Division by gender: 44 male patients (95.65%) and 2 female
      patients (4.35%). WORKING RESULTS: The average age of patients was 38.8 +/- 2.79
      (21-60 years of age); for the patients treated operationally 37.1 +/- 3.98 years
      of age, for the patients treated non-operationally 40.2 +/- 2.39; 28 right side
      patients (60.86%), 18 left side patients (39.14%); Surface infection detected on
      1 patient (2.17%); 2 patients with partial rupture, while 3 patients had complete
      rupture during early rehabilitation period after immobilization was taken off.
      Complete rupture detected on 3 patients (6.25%) has been recovered surgically.
      Thromboembolism noticed on 3 patients (6.52%) while 2 patients (4.34%) were
      affected by pulmonary embolism. Tendon elongation present on 3 patients (Magnetic
      Resonance (MR) Diagnostics) and on 1 patient reoperation was performed 3 months
      after the primary surgical intervention. CONCLUSION: This study didn't show
      significant statistical difference between two ways of treatment, but early
      immobilization is recommended because of better results. In case of Achilles
      tendon rupture, the advantage should be given to the surgical treatment,
      especially if younger population is treated.

PMID- 24669582
TI  - Somatostatin-producing duodenal carcinoma: clinicopathological description of a
      case.
AB  - Somatostatinomas are rare functioning neoplasms usually arising in the pancreas
      and duodenum. They are seldom associated with typical clinical symptoms. Their
      diagnosis is confirmed only by histological and immunohistochemical studies and
      the presence of specific hormones. Two distinct clinicopathological forms of
      somatostatinoma exist: duodenal and pancreatic somatostatinomas. Clinically,
      compared to pancreatic somatostatinomas, duodenal somatostatinomas are more often
      associated with nonspecific symptoms and neurofibromatosis, but less often with
      somatostatinoma syndrome or metastasis. We report a case of somatostatin
      producing duodenal carcinoma in a 45-year-old female with neither
      neurofibromatosis nor somatostatinoma syndrome. Abdominal computed tomography
      showed a 18 mm mass in the duodenum which had given rise to multiple lymph node
      metastases. Although the endoscopic biopsies were free of malignancy, the patient
      subsequently underwent Whipple's operation for the duodenal mass.
      Immunohistochemical analysis confirmed the diagnosis of somatostatin-producing
      carcinoma.

PMID- 24669583
TI  - WHO Expert Committee on Biological Standardization. Sixty-third report.
AB  - This report presents the recommendations of a WHO Expert Committee commissioned
      to coordinate activities leading to the adoption of international recommendations
      for the production and control of vaccines and other biologicals, and the
      establishment of international biological reference materials. Following a brief
      introduction, the report summarizes a number of general issues brought to the
      attention of the Committee. The next part of the report, of particular relevance
      to manufacturers and national regulatory authorities, outlines the discussions
      held on the development of revised WHO Recommendations and Guidelines for a
      number of vaccines, blood products and related substances. Specific discussion
      areas included the development of WHO guidance on the quality, safety and
      efficacy of poliomyelitis vaccines; recombinant malaria vaccines; diphtheria
      vaccines; tetanus vaccines; combined vaccines based on diphtheria and tetanus
      vaccines; and Japanese encephalitis vaccines. Subsequent sections of the report
      then provide information on the current status and proposed development of
      international reference materials in the areas of vaccines and related
      substances; blood products and related substances; in vitro diagnostic device
      reagents; biotherapeutics other than blood products; and antibiotics. A series of
      annexes are then presented which include an updated list of WHO Recommendations,
      Guidelines and other documents on biological substances used in medicine (Annex
      1), followed by a series of WHO Recommendations and Guidelines adopted on the
      advice of the Committee (Annexes 2-7). All additions made during the meeting to
      the list of International Standards and Reference Reagents for biological
      substances maintained by WHO are then summarized in Annex 8, and are also
      available at: http://www. who.int/biologicals.

PMID- 24669584
TI  - Measles: still a problem? Still a menace? Still here.

PMID- 24669585
TI  - Undifferentiated carcinoma of pancreas: a rare entity with aggressive behavior
      and possible genetic link.
AB  - An aggressive undifferentiated carcinoma of pancreas is a rare tumor, especially
      with a strong personal and family history of malignant melanoma. Limited
      literature review and few case reports described a genetic association between
      distinct types of pancreatic cancer and malignant melanoma. CASE REPORT: We
      present an uncommon case of an aggressive undifferentiated carcinoma of the
      pancreas in a 50-year-old Caucasian female. Initially, she presented with
      intermittent epigastric postprandial pain and mild nausea. A computed tomography
      scan of the abdomen showed a 5 cm heterogenous pancreatic tail mass, which on
      biopsy was found to be a poorly differentiated non-small cell carcinoma. Past
      medical history included malignant melanoma, with extensive family history of
      pancreatic cancer and malignant melanoma. However, not genetically confirmed, a
      hereditary pancreatic linkage was highly suspected. A week later, repeat computed
      tomography demonstrated tremendous enlargement of the pancreatic tail mass.
      Within a few weeks, the patient developed aggressive metastasis in various organ
      systems, followed by multiple surgeries. An emergent first round of chemotherapy
      was started, followed by an intensive care unit stay, and she eventually died.
      CONCLUSION: Our case exposes the aggressive behavior of undifferentiated
      carcinoma of pancreas, along with possible hereditary link between pancreatic
      cancer and malignant melanoma.

PMID- 24669586
TI  - Hyperparathyroidism: a rare mediastinal presentation of an ectopic adenoma.
AB  - The aortopulmonary window is a rare location of an ectopic parathyroid gland, but
      one that must be considered in persistent primary hyperparathyroidism despite
      previously attempted parathyroidectomy. Multiple diagnostic studies, including
      nuclear scans and anatomical imaging techniques, are crucial for identification
      of a parathyroid gland in the mediastinum and prevention of unnecessary
      exploratory surgical intervention. This case report presents a 55-year-old female
      patient with persistent hyperparathyroidism following a neck exploration and
      thyroidectomy for a parathyroid adenoma. Serial sestamibi scans and CT imaging
      over the subsequent few years were suggestive, but not diagnostic, of a
      mediastinal adenoma. Four years after the initial surgery, however, imaging
      studies identified the development of a soft tissue mass with increased uptake in
      the aortopulmonary window. A median sternotomy was performed at that time. An
      ectopic parathyroid gland was identified during surgery between the aortic arch
      and the bifurcation of the pulmonary artery, as demonstrated on imaging and
      confirmed by frozen section. Two years following the sternotomy, the patient
      remains symptom free with calcium and parathyroid hormone (PTH) levels within
      reference ranges.

PMID- 24669587
TI  - Changes coming in pain management?

PMID- 24669588
TI  - Communicating with a patient's family, friends, and others.

PMID- 24669589
TI  - Using portability and trusts to avoid estate taxes.

PMID- 24669590
TI  - Quality focus: Current guidelines for colorectal cancer prevention and detection.

PMID- 24669591
TI  - DAKOTACARE update: Clinical trials: the days of whine and roses.

PMID- 24669592
TI  - Extenuating circumstances: William Osler and Stonewall Jackson: a footnote to
      history.

PMID- 24669593
TI  - A doctor's story.

PMID- 24669594
TI  - Vaginal birth after caesarean section.

PMID- 24669595
TI  - Effect of estradiol levels on pregnancy outcome in obese women.
AB  - BACKGROUND: The incidence of obesity in women of reproductive age group has
      encountered problems of infertility with frequent referral to reproductive
      clinics. In order to know whether increase in body mass index (BMI) is associated
      with poor reproductive outcome, current study was aimed to relate women's BMI,
      estradiol (E2) levels, and clinic pregnancy rates after intra cytoplasmic sperm
      injection (ICSI). METHODS: Quasi experimental design of 323 women was conducted
      from June 2010 till August 2011. Women were grouped on the basis of BMI; Group A,
      BMI < 18 (underweight); Group B, BMI 18-22.9 (normal weight); Group C, BMI 23
      25.9 (overweight); and Group D, BMI > or = 26 (obese). Procedure of ICSI
      commenced by down regulation of ovaries followed by controlled ovarian
      stimulation. Oocyte pickup was done 36 hours after ovulation induction by hCG,
      eggs fertilised in vitro were graded and only blastocysts were transferred. Serum
      samples of basal E2, peak E2 (day of hCG administration) and mid-luteal E2 (7
      days after egg collection) measured by ELISA were compared in all BMI groups.
      Pregnancy outcome of these was categorised as: no conception beta-hCG < 5 mlU/ml,
      preclinical abortion with beta-hCG > 5 mlU/ml, no cardiac activity on
      transvaginal scan (TVS) and clinical pregnancy with beta-hCG >5 mlU/ml and
      cardiac activity on trans-vaginal scan. RESULTS: Obese women with BMI > or = 26
      had lowest basal, peak and mid-luteal E2 with minimum clinical pregnancy rates
      compared to rest of the groups. CONCLUSION: A high BMI is associated with
      decreased E2 levels in all phases of ovarian cycle and has a negative impact on
      pregnancy outcome.

PMID- 24669596
TI  - Management of thrombocytopenia and flu-like symptoms in dengue patients with
      herbal water of Euphorbia hirta.
AB  - BACKGROUND: Incidence of dengue increased 30 fold between 1960 and 2010. This
      increase is believed to be due to a combination of urbanisation, population
      growth, increased international travel, and global warming. We tried to find out
      the effect of herbal water of Tawa-tawa, also called Euphorbia hirta, on the flu
      like symptoms and blood parameters especially on thrombocytopenia. METHODS: Total
      125 patients with confirmed dengue fever admitted in medical ward of Sir Ganga
      Ram Hospital Lahore were included in this experimental study. Duration of study
      was 3 months. Patients were divided into 2 groups, i.e., group A (ages between 30
      to 55 years) and group B (ages between 14 to 25 years). A blood sample was
      obtained on the day of enrolment and after 24 hours of using Tawa-tawa. The
      variables used were platelet count, haematocrit (HCT), WBC count, serum AST, ALT,
      IgM/IgG. RESULTS: In men, platelet count was < 25,000 and in women, it was >
      50,000. Haematocrit were >40% in men and 30-40% in women. TLC in a range of 4,000
      11,000/mm3 was observed in both males and females. IgM 'haemagglutination'
      antibody titres (> 1:160) was observed in 71.3% females and 50% males. Serum AST
      was > 40 IU/L in 38% females and 36% males. Serum ALT was > 40 IU/L in 9.5%
      females and 12% males. In both group A and B platelet count and TLC were
      increased nonsignificantly after herbal water of Euphorbia hirta (E. Hirta).
      Haematocrit value decreased nonsignificantly after using the herbal water. Over
      70% of patients showed moderate increase in their platelet count. However
      leucopoenia improved significantly after the use of aqueous extract of E. hirta.
      A marked recovery in fever and flu like symptoms was observed. CONCLUSION: In
      over 70% patients there was improvement in platelet count, TLC, fever, and flue
      like symptoms.

PMID- 24669597
TI  - Comparison between panretinal photocoagulation and panretinal photocoagulation
      plus intravitreal bevacizumab in proliferative diabetic retinopathy.
AB  - BACKGROUND: Patients with diabetes often develop ocular complications. The most
      common and most blinding of these complications, however, is diabetic
      retinopathy. The objective of this study was to compare the retinal neovessels
      regression in Proliferative Diabetic Retinopathy (PDR) treated with Pan Retinal
      Photocoagulation (PRP) versus panretinal photocoagulation plus Intra Vitreal
      Bevacizumab (IVB). METHODS: A comparative study was conducted at Khyber Institute
      of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar from 1st
      October 2010 to 31st August 2011. A total of 54 eyes were randomised into two
      groups. Neovessels status was assessed before and at every follow up visit. Neo
      Vessels on the Disc (NVDs) were assessed as per percentage of NVD occupying the
      disc surface whereas Neo Vessels Elsewhere (NVE) were also assessed as per
      reference to disc surface diameter. RESULTS: Neovascularization on the disc was
      40 +/- 5% at presentation which increased to 50 +/- 7% on 30th day and stabilised
      to 40 +/- 6% on day 90 in PRP group. In PRP-plus group, 40 +/- 7% NVD regressed
      to 10 +/- 5% on 30th day and 11 +/- 3% on day 90. The NVE in PRP group was 2 +/-
      0.75% at baseline, 2.25 +/- 0.75% on 30th day, and 2.00 +/- 0.50% on day 90. In
      PRP-plus group it was 2 +/- 0.50% at baseline, 1 +/- 0.5% on day 30, and 0.75 +/-
      0.25% on day 90. On day 90 both the groups had highly significant different NVD
      (p = 0.00008) and NVE (p = 0.0001). CONCLUSION: Intra Vitreal Bevacizumab in
      short term is effective as adjunctive treatment to PRP with early and higher rate
      of retinal neovessels regression than PRP alone in PDR patients.

PMID- 24669598
TI  - Sodium hyaluronate eye drops in the treatment of dry eye disease: an open label,
      uncontrolled, multi-centre trial.
AB  - BACKGROUND: Dry eye disease (DED) is one of the most frequently encountered
      ocular morbidities. The objective of this study was to assess the performance of
      sodium hyaluronate eye drop for eight weeks in patients with DED. PATIENTS AND
      METHODS: This was a multi-centre, open-label, uncontrolled clinical trial carried
      out at different centres of Pakistan, from August 2009 to November 2010. A total
      of 250 diagnosed patients of Dry Eye who met the inclusion criteria were included
      in the study. After informed written consent, all patients having at least 2 of
      the Dry Eye symptoms, and at least 1 of the tests (Tear Film Break-up time (TBUT)
      < or = 10 second, Schirmer's test < or = 6 mm/5 min, and positive corneal
      staining) were enrolled. Tolerability/safety assessments consisted of monitoring
      and recording of adverse events and physical examinations at baseline, 4th week
      and 8th week. RESULTS: Out of 250 allocated patients 13 dropped out. The mean age
      of the patients was 47.6 +/- 13.8 year and out of 237 patients 86 (36.3%) were
      men and 151 (63.7%) were women. At the initial visit the foreign body sensation
      was 80%, itching 68%, burning 58%, watering 38%, photophobia 38%, and feeling of
      dryness was 16%. At the 3rd visit the foreign body sensation decreased to 32%,
      itching to 32%, burning to 20%, watering to 12%, photophobia to 18%, and feeling
      of dryness to 14%. CONCLUSION: Sodium hyaluronate has a beneficial effect on the
      conjunctival epithelium in a well-defined and homogeneous population of patients
      with dry eye and can be considered useful for the treatment of dry eye.

PMID- 24669599
TI  - Maternal and foetal outcome in gestational diabetes.
AB  - BACKGROUND: Gestational diabetes is impaired carbohydrate metabolism first
      diagnosed in pregnancy. Knowledge of diabetes dates back to centuries before
      Christ. Objective was to describe maternal complications during antenatal period
      and Maternal and neonatal outcome in gestational diabetes mellitus. METHODS: This
      Descriptive observational study was conducted at Department of Obstetrics and
      Gynaecology, Alhada Military Hospital, Taif, KSA. It was done during January
      December 2009 to measure maternal and neonatal outcome. Hundred pregnant women
      diagnosed through glucose tolerance test as diabetic were enrolled as study
      subjects. All the subjects were enrolled and followed regularly at Obstetric and
      Gynaecology out-patient Department of Alhada Military Hospital, Taif. Blood
      glucose level was controlled either by diet or by diet and insulin. Study
      subjects were hospitalised for adjustment of dose of insulin and for management
      of complications. Foetal well being was assessed by kick count, cardiotocography
      and ultrasound. Time and mode of delivery was decided at 36 week of gestation.
      Intra-partum maternal blood glucose level was monitored and foetal monitoring was
      done by cardiotocography. RESULTS: Total numbers of women delivered were 2,858.
      Hundred cases of diabetes mellitus during pregnancy were studied. Eighty-eight
      patients were above 25 years of age, multiparous ladies with gestational diabetes
      in 76% of cases. Insulin was required in 64% of patients. Polyhydramnios was most
      common maternal complication. Two out of 100 had spontaneous miscarriage; 14
      underwent preterm delivery while 84 reached term with two intrauterine death.
      Caesarean section was carried out in 58 patients. Total number of babies
      delivered alive were 92. There were 4 neonatal deaths. Hyperbilirubinemia was the
      most common neonatal complication. CONCLUSION: It was concluded that early
      detection, constant supervision, strict glycaemic control, delivery with
      intensive intrapartum monitoring and facilities of expert neonatologist can
      result in good maternal and foetal outcome, without much morbidity.

PMID- 24669600
TI  - Intraocular pressure measurement: Goldmann Applanation Tonometer vs non contact
      airpuff tonometer.
AB  - BACKGROUND: An accurate assessment of Intraocular pressure (IOP) is vital in
      establishing diagnosis of Glaucoma and decision making regarding various
      treatment modalities available. The purpose of this study is to compare Goldmann
      Applanation Tonometer (GAT) with Air puff tonometer. METHODS: Cross-sectional
      comparative study conducted. 73 eyes from 73 patients were included in this study
      and intraocular pressure (IOP) was measured by GAT and PT100 at Sheikh Khalifa
      Bin Zayed Hospital, Muzaffarabad, Benazir Shaheed Teaching Hospital, Abbottabad.
      RESULTS: Mean age of the patients was 53.17 +/- 13.80 years. Mean IOP
      measurements showed significant differences in measurements performed by the two
      tonometers (p < 0.05). Correlation revealed significant relation between PT100
      and GAT (Pearson's correlation 0.715, p < 0.01). CONCLUSIONS: Compared to non
      contact air-puff tonometer, the Goldmann applanation tonometer is a reliable and
      consistent technique for measurement of intraocular pressure.

PMID- 24669601
TI  - Vesicovaginal and rectovaginal fistulas: 12-year results of surgical treatment.
AB  - BACKGROUND: Although the magnitude of obstetric fistulae (OF) is reported to have
      decreased in industrialised countries, it is still a major problem in developing
      countries especially the fistulae resulting from obstructed labour. Vesico
      vaginal fistulae (VVF) are the most common and the most frequent type of
      urogenital fistulas. In most cases, surgery is required for treatment. The aim of
      this study was to analyse the results of surgical treatment of VVF and
      Rectovaginal Fistulae (RVF) in a tertiary level institution over 12 years period.
      METHODS: This retrospective study was conducted at Ayub Teaching Hospital, and
      Women and Children Hospital, Abbottabad. It included records of a total of 74
      patients who were surgically treated from 2001 to 2012. RESULTS: Cause of VVF was
      obstructed labour in 81.08% of cases, and it was iatrogenic in 18.92% cases. In
      the surgical treatment of primary VVF transvaginal approach was used in 91.9%,
      while transabdomenal approach was used in 2.7% cases. In 54.1% of cases the VVF
      healed after a single surgical intervention, while in 45.9% cases more-than-one
      operations were required. CONCLUSION: Birth trauma is still a major cause of
      VVF/RVF in our region. Prevention is possible with provision of sufficient health
      care and public awareness. Successful repair is possible with 1st surgery.

PMID- 24669602
TI  - Efficacy of gastric aspiration in reducing post-tonsillectomy vomiting in
      children.
AB  - BACKGROUND: Nausea and vomiting are two of the most frequently experienced
      postoperative side effects complicating one third of the cases. The objective of
      this study was to determine the effectiveness of gastric decompression in
      reducing the incidence and complications associated with post-tonsillectomy
      vomiting in children. METHODS: This was a randomised control study conducted at
      the ENT Department, Ayub Teaching Hospital Abbottabad from January to June 2012.
      Patients included in this study were divided into two groups, group A undergoing
      gastric aspiration and group B not undergoing gastric aspiration. Gastric
      aspiration was done with an oro-gastric tube placed under direct visualisation
      while the patient was still under general anaesthesia. The incidence of vomiting,
      episodes of vomiting and the need for rescue anti-emetic prophylaxis were noted.
      RESULTS: A total of 54 patients were included in the study. Their ages ranged
      from 5 to 12 years with mean age 7.85 +/- 2.18 years. No statistically
      significant difference (p > 0.05) was noted between the two groups for the
      patients experiencing vomiting (33% vs 41%, p = 0.389), the mean number of
      episodes of vomiting (0.71 vs 0.88, p = 0.555), and patients requiring rescue
      anti-emetics (11% vs 15%, p = 0.500). CONCLUSION: Gastric aspiration during
      tonsillectomy is not useful in reducing post-tonsillectomy vomiting.

PMID- 24669603
TI  - Effect of ascorbic acid and alpha tocopherol on immune status of male Sprague
      Dawley rats exposed to chronic restraint stress.
AB  - BACKGROUND: The immune system provides protection against infectious diseases or
      other insults. Psychological stress may alter antibody production through
      neurobiological pathways. Antioxidant supplementation is thought to improve
      immune status and thereby reduce infectious morbidity. The aim of this study was
      to determine the preventive effect of ascorbic acid and alpha tocopherol on
      immune status of rats exposed to chronic restraint stress. METHODS: A total of
      150 healthy male Sprague Dawley rats were included in the study. They were
      divided into 5 groups, each comprised of 30 rats. Group I was the control group
      on normal diet. Group II rats were exposed to chronic restraint stress for 6
      hours daily for 15 days, without antioxidant supplementation, whereas rats of
      groups III, IV and V were given supplementation of ascorbic acid or alpha
      tocopherol or both respectively, for one month prior to exposure of rats to
      chronic restraint stress. Total leukocyte count (TLC) and lymphocyte counts was
      done, and serum immuno-globulins (IgG, IgA, IgM, and IgE) levels were estimated
      using ELISA. RESULTS: Total leukocyte and lymphocyte counts and serum IgA, IgE,
      IgG, and IgM levels were found significantly (p 0.001) decreased in rats exposed
      to chronic restraint stress compared to the rats not exposed to the restraint
      stress. The combined supplementation of ascorbic acid and alpha tocopherol
      significantly (p 0.001) prevented the decline in total leukocyte and lymphocyte
      counts and serum immuno-globulins compared to the administration of either of the
      two antioxidants. CONCLUSION: Antioxidants (ascorbic acid and alpha tocopherol)
      given in combination produce greater beneficial effect in improving the immune
      status of rats exposed to chronic stress than individual supplementation of
      either ascorbic acid or alpha tocopherol.

PMID- 24669604
TI  - Efficacy of telmisartan and atenolol in management of essential hypertension.
AB  - BACKGROUND: Telmisartan and atenolol are widely used in the management of
      essential hypertension. This study was conducted to compare the efficacy of these
      two drugs in management of patients of essential hypertension. METHODS: Diagnosed
      patients of essential hypertension were selected. Therapeutic option
      (telmisartan/atenolol) was allocated to the patients by lottery method and they
      were divided into two groups. The patients were followed on subsequent visits (4
      in total) and their sitting systolic and diastolic blood pressures were recorded.
      RESULTS: Total number of 180 patients were divided into two treatment groups
      (i.e., telmisaran and atenolol). Forty percent were male and 60% were female.
      Majority of the patients were of age group 56-75 years. Telmisartan reduced
      systolic and diastolic blood pressure significantly compared to atenolol at the
      end of 8 weeks of treatment (p = 0.000 and 0.016 respectively). CONCLUSION:
      Telmisartan 80 mg once daily is more effective than atenolol 50 mg once daily in
      lowering systolic and diastolic blood pressure at the end of 8 weeks of
      treatment.

PMID- 24669605
TI  - Peri-procedural outcome of saphenous vein graft intervention.
AB  - BACKGROUND: Patients who develop recurrent myocardial ischemia after coronary
      artery bypass graft (CABG) surgery are often referred for percutaneous coronary
      intervention. The objective of this study was to evaluate the clinical
      characteristics and peri-procedural outcomes in patients with prior CABG referred
      for percutaneous coronary intervention (PCI) over a 3 year period. METHODS: Data
      were collected on patients who underwent coronary interventional procedures
      following CABG surgery. We evaluated angiographic procedural success and
      immediate outcome among patients who had undergone such procedures from Nov 2006
      to Oct 2009 (n = 113). RESULTS: Patients in the 2006-2009 cohort had mean age
      58.2 years, more patients were male (109 vs 4) and were more likely to have
      hypertension (57.5%), hyperlipidaemia (72.6%) and family history of ischemic
      heart disease (IHD) (65.5%), but less likely to have smoking (42.5%). Acute
      closure of stent leading to procedural failure was seen in 1 (0.9%) patient, sub
      acute thrombosis of stent was seen in 1 (0.9%) patient, dissection or perforation
      of target vessel was seen in 3 (2.7%) and 1 (0.9%) patients respectively. Slow
      flow phenomenon was seen in 13 (11.5%) and post-procedural cardiac enzymes were
      raised in 6 (5.3%) patients. CONCLUSION: Success rates of saphenous vein graft
      (SVG) intervention and survival rate have improved with time as a result of
      improvements in technique and greater use of stents, filter devices and
      adjunctive medications.

PMID- 24669606
TI  - Adherence to OTC directory--the perception of community pharmacists in Saudi
      Arabia.
AB  - BACKGROUND: Worldwide Ministries of Health (MoH) are encouraged to publish an
      updated Over-the-Counter (OTC)-Directory that pharmacists should adhere to in
      dispensing non-prescription medications. The Saudi Ministry of Health has
      published the OTC-Directory in the year 2000, and since then, it was readily
      available to all practicing pharmacists at no cost. This study was aimed to
      investigate the knowledge of practicing pharmacists in Riyadh, Saudi Arabia,
      regarding permitted self-prescription medications (i.e., OTC-Directory), as well
      as pharmacists professional competence and adherence at dispensing OTC drugs
      without prescription. METHODS: The study was cross-sectional by design. A
      computer generated list of simple random sampling was used to select the
      pharmacies out of 1,500 working in Riyadh. The data was collected from 384
      randomly selected community pharmacies by questionnaire using direct
      investigation method and the total respondents were 405. Associations between
      qualitative variables were observed using Pearson Chi-square and Fisher Exact
      test. RESULTS: Four hundred and five (405) pharmacists participated in the survey
      of which 100% were males and 362 (89.4%) were below the age of 40 years. Majority
      of them (361, 88.9%) were holding bachelors degree. Almost one-third of the
      respondents (123, 30.4%) were not aware of the existence of the Saudi OTC
      Directory. The pharmacists' geographical location, nationality and attendance of
      CME activity had significant association with knowledge about the OTC-directory
      (p < 0.05). Two hundred and eighty-two (69.6%) of the pharmacists who had
      knowledge about Saudi OTC-directory did not comply with its guidelines.
      Pharmacists with higher degrees were more observant of the OTC-Directory as
      compared to those with diploma and Bachelor Degree (p = 0.014). CONCLUSIONS:
      There is significant non-compliance of OTC-directory by the community pharmacists
      while providing non-prescription drugs in Riyadh, Saudi Arabia.

PMID- 24669607
TI  - Malignant phyllodes tumour of the breast.
AB  - BACKGROUND: Malignant Phyllodes Tumour (MPT) is considered to be a rare disease
      of the breast. The most frequent clinical presentation of a MPT is a rapidly
      growing breast lump. METHODS: Consecutive cases of MPT registered between Jan 1,
      1995 and Dec 31, 2012 at the Shaukat Khanum Memorial Cancer Hospital and Research
      Centre, Lahore, Pakistan, were reviewed, to obtain information on age, tumour
      size, treatment given, disease-free survival, and overall survival. Disease-free
      survival was computed between the dates of surgery and recurrence, whereas, the
      overall survival time between the dates of diagnosis and last contact, both in
      months. RESULTS: A total of 101 cases of Phyllodes tumour were recorded. These
      included: malignant tumours (42) benign (27), and borderline (32). Malignant
      Phyllodes tumours (42 cases) were studied further and 41 included for additional
      analysis. The mean age of the women in the study was 40.3 +/- 12.5 (22-72 years).
      Of the 33 patients who were disease-free after surgery, 15 had a recurrence,
      whereas, 18 did not have a recurrence. In those who had surgery alone versus
      those who received radiation treatment in addition to surgery, the median disease
      free survival was 117 and 44.2 months, respectively. The mean overall survival
      time was 33.7 months. CONCLUSION: In this study, patients presented at a younger
      age than in other studies. Further exploration into molecular, biologic,
      geographic, and socioeconomic factors is needed to clearly understand the
      epidemiology of this disease in our population.

PMID- 24669608
TI  - Knowledge practice gaps about needle stick injuries among healthcare workers at
      tertiary care hospitals of Pakistan.
AB  - BACKGROUND: The aim of our study were to assess the knowledge and practice gaps
      about Needle Stick Injuries (NSIs) and their associated factors among Health Care
      Workers' (HCWs) at tertiary care hospitals of Pakistan. METHODS: A cross
      sectional study was conducted in two tertiary care teaching hospitals in Karachi,
      Pakistan, representing both private and public health sector. During the months
      of January to May 2008, trained medical graduates interviewed 497 HCWs (Doctors
      and Nurses) who were working in those particular hospitals for more than a year
      and were willing to participate in the study. RESULTS: Overall the knowledge
      about transmission of HBV HCV and HIV was good. However, 19.1 and 12.3% HCWs had
      misconception about the transmission of malaria and tuberculosis by NSIs; more
      female and working as a nurse. Furthermore, a large number of participants had
      lack of knowledge for the transmission of infectious mononucleosis. Over two
      third of study subjects were not vaccinated for hepatitis B infection, again more
      females (p = 0.002) and nurses (p < 0.001). Large numbers of study participants
      were not wearing protective cloths, and do not us sharp containers. Similarly,
      preponderance of study subjects does not avoid breaking needle by hands and leave
      syringes open; these poor practices are significantly more prevalent among those
      working for more than five years and doctors (p = 0.003). CONCLUSION: In addition
      to lack of knowledge, poor practices were reported in this study. Proper
      curriculum reform and training are required to protect the health Care workers
      and patients. Further research and interventions are suggested in this regards.

PMID- 24669609
TI  - Frequency and characterisation of pancytopenia in megaloblastic anaemia.
AB  - BACKGROUND: A wide variety of clinical conditions, that primarily or secondarily
      affect the bone-marrow may present with pancytopenia, one of such conditions is
      megaloblastic anaemia. The purpose of this study was to determine the frequency
      and nature of pancytopenia in megaloblastic anaemia. METHODS: This was a
      prospective, cross-sectional descriptive study conducted in Medical Units, Ayub
      Teaching Hospital, Abbottabad, Pakistan during July 2010-January 2011. Total 90
      patients were included in this study. Data were collected including history,
      clinical examination, haemoglobin level, mean cell volume, bone marrow
      examination and peripheral smear examination. RESULTS: Of total 90 patients, 54
      were male and 36 were female. Mean age was 28 +/- 15.84 years. Common presenting
      features were weakness, fever and bleeding manifestations. Pancytopenia was
      present in 63 (70%) patients. Most common presenting feature related to anaemia
      was weakness (80%). Bleeding manifestations, related to low platelet count were
      found in 35 (39%) patients. Physical Examination findings were: pallor (100%),
      splenomegaly (33%), bleeding manifestations (25%), hepatomegaly (17%), and
      hepatosplenomegaly (19%). Mean peripheral blood findings of the study population
      included haemoglobin level (6.25 g/dL), total leukocyte count (2818.7/microL),
      platelet count (44040/uL), and reticulocyte count (1.7%). Mean values for red
      cells indices included red blood cells count (2.6 million/uL), mean corpuscular
      volume (114.3 fL), mean corpuscular haemoglobin (27.3 pg) and mean corpuscular
      haemoglobin concentration (31.8 g/dL). CONCLUSIONS: In megaloblastic anaemia,
      pancytopenia is a common and important clinical and haematological problem.
      Patients should be properly investigated for pancytopenia and its causes because
      many of them are completely curable while others are manageable. This will help
      to reduce patients' suffering, improve quality of life and prolong survival.

PMID- 24669610
TI  - Treatment outcome of HCV infected paediatric patients and young adults at
      Karachi, Pakistan.
AB  - BACKGROUND: Scanty data are available regarding outcome of children and young
      adults treated conventionally for Hepatitis C. The present study was undertaken
      to evaluate the outcome of paediatric and young adult patients treated with PEG
      IFN-alpha or conventional interferon (IFN) plus Ribavirin at a public sector
      hospital of Karachi. METHODS: This was an observational study, conducted at
      Sarwar Zuberi Liver Centre, Civil Hospital Karachi, from 2007 to 2010. Patients
      up to 20 year of age were tested for Anti-HCV antibodies by 4th generation ELISA
      and in positive cases HCV RNA was done by PCR. Patients with HBV, HIV and other
      comorbids such as thalassaemia minor, haemophilia, kidney disease, and co
      existing active illness other than HCV were excluded. Depending upon the
      genotype, patients were treated for 24-48 weeks with IFN 3 MIU x3 per week or PEG
      IFN-alpha (1.5 microg/Kg) per week plus Ribavirin 15 mg/Kg/day. Nearly all
      patients were followed till the end of treatment. RESULTS: Mean age of 55
      patients, was 18.42 +/- 2.59 years (range 9-20 years) and BMI 19.56 +/- 2.36
      Kg/m2. Females were 70.9% (n = 39). More than 80% had genotype 3 (subtype a or
      b). Remaining had genotype 1, 4 or mixed. Slight decreases in haemoglobin,
      platelet and white cell count at 1, 3 and 6 months of treatment were noted. No
      significant side effects were noted. There was a marked decrease in the ALT post
      treatment (pre-treatment values 72.69 +/- 50.73 versus post-treatment 24.81 +/-
      14.09 IU/l). End-treatment response (ETR) was 90.9%; of these sustained viral
      response (SVR) was achieved in 86.3%. CONCLUSION: HCV infected paediatric and
      young adult patients treated with PEG-IFN-alpha/or conventional interferon plus
      Ribavirin (combination therapy) achieved an ETR of 90.9% and SVR of 86.3%.

PMID- 24669611
TI  - Prevalence, evaluation and management of preoperative anaemia in the elective
      general surgical patients.
AB  - BACKGROUND: Anaemia is the commonest haematological problem in the preoperative
      patients. Often it is a sign of underlying disease or associated co-morbid
      condition. A low haemoglobin level is associated with an excess risk in surgical
      procedure and its outcome. Therefore an understanding of any cause, evaluation
      and any potential treatment is crucial in the preoperative setting. Our objective
      was to determine prevalence, evaluation and management of preoperative anaemia in
      the elective general surgical patients. METHODS: Prospective observational study
      in Surgical Unit-II, Liaquat University Hospital Jamshoro from July 2008 to June
      2009. One hundred and twenty-five anaemic cases were included in the study, with
      haemoglobin level < 10 g/dl. Their age ranged from 13 to 70 years. They were
      evaluated for preoperative anaemia in relation to surgical problems and
      associated any co-morbid conditions. RESULTS: Out of 830 patients during the
      study period, 125 patients were anaemic with haemoglobin level 2.1-9.9 g/dl.
      Fifty-six (44.8%) were male and 69 (55.2%) were female, and 68.5% patients were
      from rural areas. Hypochromic microcytic was seen in 101 (80.8%) cases. Commonest
      surgical problem associated with anaemia was malignancies (27.2%) followed by
      haemorrhoids (20%) and tuberculosis of abdomen (14.4%). Majority of patients
      (52%) were managed on oral iron supplements while 48% received blood
      transfusions.

PMID- 24669612
TI  - Effect of visfatin on testicular steroidogenesis in purified Leydig cells.
AB  - BACKGROUND: Lower testosterone levels have been reported in men suffering from
      diabetes mellitus. Men with insulin resistance states such as obesity and type 2
      diabetes mellitus have significantly lower testosterone levels than age-matched
      normal weight and non-diabetic controls. Adipose tissue secretes variety of
      adipokinesincluding adiponectin, resistin, visfatin, TNF-alpha. The study was
      designed to study the effect of visfatin on testicular steroidogenesis in
      purified Leydig cell in vitro. METHODS: Leydig cells of Sprague Dawley rats were
      isolated and purified by Percoll. Cells were incubated for 3 hours with/without
      visfatin in the presence/absence of LH and intracellular signalling blockers
      including PKC blocker, PKA blocker and Raf1/Ras blocker. Cell culture extracts
      were stored at -80 before analysis for levels of testosterone hormone by ELISA.
      RESULTS: Visfatin increased testosterone production (p < 0.001) from cultured
      Leydig cells. Raf1/Ras blocker decreased visfatin induced steroidogenesis (p <
      0.001). CONCLUSION: Visfatin increased testicular steroidogenesis from Leydig
      cells in vitro models and operates through variety of enzymes, but especially
      through Ras/Raf1 kinase enzymes.

PMID- 24669613
TI  - Risk factors among HIV positive/AIDS patients: a prospective study at a tertiary
      care referral centre.
AB  - BACKGROUND: HIV/AIDS is a global problem, South Asia and Africa bearing the
      maximum burden. The incidence is reported to be rising in Pakistan. It is
      important to document the prevalence of various risk factors in our population so
      that appropriate measures could be taken for preventing emergence of new cases.
      Objectives were to identify the possible etiological factors/high risk behaviour
      in cases diagnosed as HIV/AIDS presenting at a tertiary care referral centre.
      METHODS: Prospective observational case series carried out over a one year period
      at HIV/AIDS referral centre at Allama Iqbal Medical College Lahore. Five hundred
      patients were included who were positive for HIV on screening devices and then
      confirmed by ELISA. All these patients were referrals from Punjab AIDS control
      programme (PACP). A detailed history was taken on a pre-designed Performa
      specially targeted to identify the known risk factors for HIV infection. RESULTS:
      Five hundred HIV positive subjects diagnosed by screening device and confirmed on
      ELISA were included in the present study. Three hundred and fourteen (63%) were
      males and 186 (37%) were females. Mean age was 35 +/- 12 years. Most prevalent
      risk factor among these patients was sexual transmission followed by intravenous
      drug abuse, injections from substandard health facilities, and transmission from
      infected spouse. CONCLUSION: HIV/AIDS is a preventable disease if the risk
      factors are avoided. Community awareness for unsafe homo and heterosexual
      practices and discouraging visits to non qualified health practitioners should be
      the top priority by PACP apart from controlling the IDUs menace.

PMID- 24669614
TI  - Use of formative assessment as an educational tool.
AB  - BACKGROUND: Though formative assessments are popular in medical education, but
      data to establish their educational benefits are lacking. This study was
      conducted to determine whether participation and performance of MBBS students in
      regular formative assessments are associated with positive outcomes and has
      measurable effects on learning. METHODS: One hundred and fifty MBBS students of
      semester II attending Biochemistry classes were studied by dividing into two
      groups till the completion of a topic. End-of-topic summative assessment marks
      were analysed with respect to the effect of participation and performance in
      formative assessments. RESULTS: Participation in formative assessments had a
      statistically significant positive relationship with summative assessment marks.
      Mean difference in formative and summative assessment marks for group that
      participated in formative assessments is 1.6 (95% CI = 0.9-2.4, p < 0.001). The
      mean difference in summative assessment marks for two groups is 3.4 (95% CI = 2.3
      4.6, p < 0.001). The mean difference in marks obtained by solving case studies
      given in Summative Assessment for two groups is 1.2 (95% CI = 0.7-1.6, p <
      0.001). CONCLUSIONS: Formative assessment not only assesses students'
      achievements but it also enables students to recognise the areas in which they
      are having difficulty and to concentrate their future efforts on those areas.
      Adequate frequency of formative assessment with immediate feedback is beneficial
      as it stimulates meaningful and multifaceted learning. The results of this study
      encourage the use of formative assessment as an educational tool in all MBBS
      subjects for they have significant positive effects on learning.

PMID- 24669615
TI  - Quantity and quality of information, education and communication during antenatal
      visit at private and public sector hospitals of Bahawalpur, Pakistan.
AB  - BACKGROUND: Information, education and communication (IEC) by health care
      provider to pregnant woman during the antenatal visit are very crucial for
      healthier outcome of pregnancy. This study analysed the quality and quantity of
      antenatal visit at a private and a public hospital of Bahawalpur, Pakistan.
      METHODS: An exit interview was conducted from 216 pregnant women by using
      validated, reliable and pre-tested adapted questionnaire. First sample was
      selected by simple random sampling, for rest of the sample selection systematic
      random sampling was adapted by selecting every 7th women for interview. Ethical
      considerations were taken. RESULTS: Average communication time among pregnant
      woman and her healthcare provider was 3 minute in public and 8 minutes in private
      hospital. IEC mainly focused on diet and nutrition in private (86%) and (53%)
      public, advice for family planning after delivery was discussed with 13% versus
      7% in public and private setting. None of the respondents in both facilities got
      advice or counselling on breastfeeding and neonatal care. Birth preparedness
      components were discussed, woman in public and private hospital respectively. In
      both settings antenatal clients were not received information and education
      communication according to World Health Organization guidelines. CONCLUSION:
      Quality and quantity of IEC during antenatal care was found very poor in both
      public and private sector hospitals of urban Pakistan.

PMID- 24669616
TI  - Comparison of outcomes between linear versus triangular flap repair techniques at
      vermilion in unilateral cleft lip repair.
AB  - BACKGROUND: Surgery for unilateral cleft lip repair has evolved over centuries.
      Many studies give detailed inside to this process of evolution of various
      techniques and their modifications. Objectives were to compare linear repair of
      Millard rotation advancement technique and triangular flap technique of Nordhoff,
      at vermilion in unilateral cleft lip repair. METHODS: This cross-sectional
      analytical study was conducted at Departments of Plastic Surgery, Services
      Institute of Medical Sciences, and WAPDA Teaching Hospital Complex, Lahore form
      Jan 2004 to Dec 2011. Patients presenting with unilateral cleft lip deformity
      were included in the study. In the early part of the study (2004-2008), only
      Millard linear repair at vermilion was the routine practice. Last consecutive 40
      cases repaired with this technique during this period were selected for the
      study. From 2009 to 2011 the unilateral cases were operated with Nordhoff
      triangular flap repair. A group of 40 consecutive cases repaired with this
      technique was also selected for the study. In both groups, the postoperative
      period exceeded one year. Results were compared for the presence of notch on
      repaired vermilion area. RESULTS: Notch was absent in 29 cases (72%) treated with
      Millard Technique whereas Noordhoff Technique Group showed a higher number of 34
      cases (85%). On other extreme, a notch of more than 1 mm was evident in two cases
      (5%) of Millard technique only and Noordhoff technique did not show this wide
      notch at vermilion. Similarly, two subgroups of 0.5 mm notch and 0.5-1 mm notch
      had a slightly higher number of cases in group dealt with Millard technique (5
      and 4 cases respectively) as compared to cases dealt by Noordhoff technique (3
      cases in each subgroup). CONCLUSION: Nordhoff triangular flap repair at vermilion
      reduces the chances of notching to minimum due to break in the linear repair in
      vermilion and also helps in reconstructing a symmetrical vermilion by bringing in
      the vermilion from lateral to medial segment.

PMID- 24669617
TI  - Ectopic pregnancy management in Ayub Teaching Hospital Abbottabad: a ten year
      survey.
AB  - BACKGROUND: Ectopic pregnancy is a common life-threatening emergency in the
      developing world. It is a cause of maternal morbidity and mortality in the first
      trimester and these mortalities can be reduced if it is properly managed. The
      objective of this study was to assess the variable clinical presentations and
      outcome of treatment of ectopic pregnancy in Ayub Teaching Hospital Abbottabad.
      METHODS: Two hundred and fifty-five patients with ectopic pregnancy managed in
      Ayub Teaching Hospital over period of 10 years, were included in the study. The
      clinical presentation, diagnostic modalities and out come of treatment were
      recorded and analysed. RESULTS: Out of 255 patients 43 (16.86%) had un-ruptured
      tubal pregnancy, 183 (71.76%) had ruptured ectopic pregnancy and 22 (8.62%) had
      chronic ectopic pregnancy. At laparotomy, salpingectomy was done in 229 (89.80%)
      patients, salpingo-ophrectomy in 2 patients (0.78%), linear salpingostomy in 15
      (5.88%) patients. Medical treatment was given to 5 patients and 8 patients were
      treated conservatively. There was no maternal mortality. CONCLUSION: In spite of
      various recent advances in the management of ectopic pregnancy, conventional
      surgical treatment by laparotomy is still the most widely used modality of
      treatment in our institution. With appropriate and prompt management, maternal
      mortality due to ectopic pregnancy can be prevented.

PMID- 24669618
TI  - Ventriculoperitoneal shunt blockage.
AB  - BACKGROUND: Hydrocephalus is the abnormal accumulation of cerebrospinal fluid
      within the ventricles and subarachnoid spaces, resulting in increased
      intracranial pressure. The treatment of choice is placement of
      ventriculoperitoneal shunt. Ventriculoperitoneal shunt blockage is not an
      uncommon complication. Objective of the study was to find out the frequency,
      causes and site of ventriculoperitoneal blockage and to compare it with other
      studies. METHODS: This case series study was conducted at Department of
      Neurosurgery Liaquat University Hospital, Jamshoro, from April 2008 to March
      2012. The records of 53 patients between 40 days to 45 years age presenting with
      blocked ventriculoperitoneal shunt were included. All the patients underwent
      thorough clinical examination and radiological investigations, and shunt revision
      done. The retrieved data was collected on proforma. Frequencies and percentages
      were calculated for categorical data. RESULTS: Out of 53 patients 28 were males,
      25 patients were females. Age of patients ranged from 40 days to 45 years. Time
      interval between the ventriculo-peritoneal shunt placement and blockage of shunt
      ranged from 2 weeks to 9 years. Out of 53 patients, 32 (69.37%) patients had
      obstruction at distal catheter, whereas 21 (39.62%) patients had ventricular
      catheter blockage. CONCLUSION: Ventriculo-peritoneal shunt blockage is one of the
      most common complications of shunt placement procedure. In this study most of the
      patients (69.37%) had distal catheter obstruction. Majority (35.84%) of the
      patients presented with shunt obstruction within one year of shunt placement.
      Shunt obstruction is common in children less than 3 years age.

PMID- 24669619
TI  - In vitro response of tracheal smooth muscle from hyperresponsive guinea pigs to
      celiprolol.
AB  - BACKGROUND: The use of beta-blockers is limited by adverse effects such as
      bronchospasm in asthmatics. Third generation beta-blockers such as celiprolol may
      show better respiratory tolerability because they lack beta-blocker induced
      broncho-constriction. METHOD: Effect of celiprolol on the histamine induced
      contraction of tracheal muscle strips prepared from ovalbumin-sensitised guinea
      pigs was studied. Using oxygenated Krebs-Henseleit solution as the nutrient
      medium, the trachealis muscle activity was measured with isometric force
      displacement transducer and recorded on 4-channel Oscillograph. RESULT:
      Celiprolol 10(-4) M shifted the concentration-response curve of histamine
      downwards and to the right. Mean of amplitude of contraction, percent responses
      and deviations when compared with the control group were significantly different
      (p < 0.05). CONCLUSION: Celiprolol antagonised histamine-induced contractions of
      tracheal muscle of guinea pigs. So it may be considered safe in patients with
      asthma. However, further clinical evaluation and exploratory work is required.

PMID- 24669620
TI  - Demographic and surgical evaluation of typhoid ileal perforation.
AB  - BACKGROUND: Typhoid perforation of small intestine is one of the most common
      causes of bowel perforation in the developing countries. The purpose of this
      study was to determine the prevalence, factors affecting prognosis, and optimal
      surgical management for typhoid perforation in Sindh. METHOD: One hundred and
      thirty patients with typhoid perforation were included in the study from July
      2005 to June 2007 in the Department of Surgery, Liaquat University Hospital,
      Hyderabad. Patients were admitted as cases of acute abdomen. Detailed history,
      clinical examination and relevant investigations were carried out. Double layer
      primary closure, primary loop ileostomy and segmental resection with end-to-end
      anastomosis were performed according to the operative findings and condition of
      the patients. Attention was paid to postoperative complications and course of the
      morbid condition. RESULTS: Majority of patients belonged to deserted areas of
      district Umerkot (n = 35, 26.93%), and Mithi (n=20, 15.38%) followed by Dadu (n =
      17.13.08%), Badin (n = 5, 11.54%), Jamshoro (n= 11, 8.46%), Hyderabad (n = 10,
      7.69%), Thatta (n = 9, 6.92%), Mirpurkhas (n = 7, 5.38%) and Sanghar (n = 6,
      4.62%). Double layer primary closure of single perforation was done in 50
      (38.46%) patients, primary loop ileostomy was performed in 68 (52.30%) patients
      and primary resection and end-to-end anastomosis was performed in 12 (9.23%)
      patients. Postoperative complications were observed in 79 (60.76%) patients.
      Wound infection was the commonest complication seen in 70 (53.84%) patients
      followed by wound dehiscence in 10 (7.69%), faecal fistula in 9 (6.92%),
      septicaemia in 8 (6.15%), postoperative chest infection in 25 (19.23%), and intra
      abdominal abscess in 15 (11.53%) patients. Ten (7.69%) patients died due to
      septicaemia and other reasons. CONCLUSION: Typhoid perforation remains a
      frequently fatal illness with high prevalence in remote areas of Sindh. Primary
      loop illeostomy is the single most successful and life saving surgical procedure
      in terms of overall morbidity and mortality.

PMID- 24669621
TI  - Laparoscopic ovarian drilling for polycystic ovarian syndrome: treatment outcome.
AB  - BACKGROUND: Anovulatory infertility due to polycystic ovarian syndrome (PCOS)
      remains the commonest cause among women of reproductive age group. Although
      clomiphene citrate (CC) remains the first choice treatment in addition to other
      medical therapies, laparoscopic ovarian drilling (LOD) is rapidly gaining
      acceptance as a second line management in patients who failed to respond to CC.
      This study was done to evaluate the efficacy of LOD in management of PCOS related
      infertility. METHODS: This was a descriptive study conducted at CMH Peshawar, CMH
      Kharian, and PAF Hospital Mushaf, from 2004 to 2011. It included 69 patients who
      underwent LOD for anovulatory infertility after being diagnosed as PCOS. Patients
      were diagnosed on the basis of their clinical, hormonal and ultrasonic findings.
      Age of the patients, features suggestive of hyperandrogenism, body mass index
      (BMI), duration of infertility, and LH/FSH ratio were noted. Patients were
      followed post-operatively for one year. RESULTS: Overall ovulation rate was
      82.61% after LOD. Thirty-one out of 69 patients ovulated spontaneously within
      first 6 weeks after LOD while 26 patients ovulated on getting treatment with CC
      in addition to LOD. Thirty-three (47.82%) patients conceived in their first year
      after surgery. About 54% of patients reported improvement in their symptoms
      related to hyperandrogenism. CONCLUSION: LOD is an established and safe method as
      a second line treatment for PCOS related infertility.

PMID- 24669622
TI  - Early recovery and stabilisation with instrumentation in anterior cervical spine
      tuberculosis.
AB  - BACKGROUND: Tuberculous infection causes destruction, caseation, and necrosis of
      cervical vertebrae or may present as an abscess. Complete recovery of
      neurological status is the rule after anterior surgical decompression and fusion,
      even in cases with complete paraplegia or tetraplegia. Neurological impairment
      and spinal deformity are the major concerns with spinal tuberculosis. Absolute
      nonoperative treatment was offered in pre antibiotic era. Since last decade great
      advances in terms of operative options drastically changed the scenario in
      management of caries spine and indications for surgery have been extended for
      early resolution of disease, quicker rehabilitation and prevention of late
      complications. METHODS: During the period from 2005 to 2012, 336 patients of
      spinal tuberculosis were admitted in Department of neurosurgery, Liaquat
      University Hospital, Jamshoro. Forty-four patients were considered for surgery.
      All 44 patients underwent decompression through anterior cervical approach
      followed by fusion with iliac bone graft and then stabilization with titanium
      locking plate. RESULTS: There were 20 males and 24 females. Neck pain was the
      chief complaint and improved in all cases. Patients had varying grades of motor
      weakness in upper and lower limbs. All the patients had good neurological
      recovery after surgery. No postoperative surgical complication found in any
      patient. CONCLUSION: Anterior cervical decompression, fusion and instrumentation
      with titanium plate fixation in patients with tuberculous spondylitis gives
      excellent results without untoward effects.

PMID- 24669623
TI  - Role of serum-ascites albumin gradient in differential diagnosis of ascites.
AB  - BACKGROUND: The classification of ascites as 'exudative' and 'transudative' based
      on ascitic fluid total protein (AFTP) has been challenged in many clinical
      conditions like cardiac ascites, patients on prolonged diuretic therapy and
      malignant ascites because it had poor diagnostic efficacy. These drawbacks have
      led to the development of another approach to classify ascites, which is based on
      Serum-Ascites Albumin Gradient (SAAG) to differentiate ascitic fluid into two
      categories: SAAG > or = 11 g/L in ascites due to portal hypertension and SAAG <
      11 g/L in ascites unrelated to portal hypertension. Objective of this study was
      to compare the diagnostic efficacy of serum/ascites fluid albumin gradient and
      ascitic fluid total protein in patients having ascites. METHODS: This Cross
      sectional comparative study was conducted in the Department of Chemical Pathology
      and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from 1st Jun
      2007 to 30th May 2008. Ninety-three patients were included in the study by non
      probability convenience sampling. The patient grouped as: (Group I) 73 cases of
      liver cirrhosis, (Group II) 14 cases of hepatoma and 6 cases of tuberculous
      ascites. Ascitic fluid specimen and 3 ml blood were obtained for ascitic fluid
      estimation of ascitic fluid albumin, total proteins and serum albumin. Diagnostic
      efficacy of SAAG and AFTP was calculated by comparing the results with clinical,
      ultrasonographic, histopathological findings, ascitic fluid cell count/acid fast
      bacilli culture and other relevant investigations. RESULTS: Seventy-three cases
      had liver cirrhosis (group I), 14 cases had hepatoma and 6 cases had tubercular
      ascites (group II). Age ranged 25-80 years with mean age 56 years. Diagnostic
      accuracy, Sensitivity, Specificity, Positive predictive value (PPV) and Negative
      predictive value (NPV) of SAAG were 96%, 97%, 95%, 98.6%, and 90% respectively,
      whereas those of AFTP were 56%, 53%,70%, 86%, and 29% respectively. CONCLUSION:
      Differential diagnosis of ascites should be based on SAAG because diagnostic
      efficacy of SAAG was significantly higher than AFTP in work-up of ascites.

PMID- 24669624
TI  - Cervical spinal injuries in moderate to severe head injuries.
AB  - BACKGROUND: Traumatic Brain Injury (TBI) is the leading cause of death in all age
      group. The incidence of CSI increases with the severity of TBI so prompt care of
      cervical spine is necessary in all patients with moderate to severe head injury.
      The objective of this study was to determine the frequency of cervical injury in
      patients with moderate to severe head injury and different types of trauma.
      METHODS: This descriptive cross sectional study was conducted in department of
      Neurosurgery Ayub Medical College, Abbottabad from October 2011 to October 2012.
      A total of 369 patients were included in this study by consecutive (non
      probability) sampling. All patients were subjected to X-rays and CT-Scan of the
      skull for evaluation of head injury. X-rays and CT scan with MRI of cervical
      spine were done for evaluation of cervical spinal injury. RESULTS: A total of 369
      patients were included in our study, out of which 276 (74.8%) were males and 93
      (25.2%) were females. Age of the patients ranged from 3-90) years with mean of
      31.93 +/- 21.35. Among these patients most common cause of injury was fall 196
      (53.1%), whereas the RTA was 159 (43.1%) and assault was 14 (3.8%). Out of the
      369 patients 42 (11.3%) were found to have cervical spinal injuries. CONCLUSION:
      The frequency of cervical injury associated with moderate to severe head injury
      remains the same in all over the world with minor difference in percentages; that
      we have observed in our study. Furthermore, we have observed that cervical injury
      is directly proportional to the severity of head injury. All the head injured
      patients should be suspected of having cervical spinal injury unless proved
      otherwise.

PMID- 24669625
TI  - Association of maternal hypertension with placental abruption.
AB  - BACKGROUND: Placental abruption is one of the leading causes of maternal
      mortality and morbidity. Many causes predispose an expecting mother to placental
      abruption, such as trauma, previous history, smoking, ethnicity and hypertension.
      The present study concentrated on maternal hypertension as a cause of abruption.
      METHODS: All subjects of this comparative study underwent a complete obstetrical
      clinical workup comprising history, general physical examination, abdominal and
      pelvic examination, and relevant investigations. The maternal condition was
      assessed and managed according to established labour ward protocols, which
      included both pharmacological and surgical intervention. Patients were allotted
      various subgroups for detailed data analysis and comparative analysis. RESULTS: A
      total of 50 cases and 50 controls for placental abruption were studied during the
      study period. Both groups were compared based on parity, gestational age,
      proteinurea, haemoglobin, and hypertension. Mean systolic blood pressure (SBP) of
      cases in this study was 155 +/- 7.8 mmHg versus mean SBP for controls was 120 +/
      14 mmHg. Mean diastolic blood pressure (DBP) of the cases was 104 +/- 6.6 mmHg
      compared to controls where mean DBP was 71 +/-11 mmHg. Among the controls, 45
      (90%) had blood pressures in the normal range. There was statistically
      significant differences between cases and controls with respect to hypertension
      (p < 0.01). CONCLUSION: Placental abruption is strongly associated with maternal
      hypertension.

PMID- 24669626
TI  - Hepatitis C virus transmission risk factors.
AB  - BACKGROUND: Hepatitis C Virus (HCV) is major health hazard. About 350 million
      people have been suffering from HCV infection in the world. HCV progresses into
      chronic liver disease in 50-80% of cases and may end up in cirrhosis. This study
      was carried out to explore the transmission of risk factors for HCV. METHODS:
      This prospective study included 210 consecutive HCV patients of either sex,
      ranging from 20-69 years of age, referred to Sheikh Khalifa Bin Zyad Hospital/
      Combined Military Hospital, Muzaffarabad, Azad Kashmir. In patients having HCV
      positive by ELISA, the PCR qualitative tests of HCV RNA were performed. A
      questionnaire was filled for every patient regarding possible risk factors.
      RESULTS: Most common risk factors among HCV patients were surgical procedures (p
      < 0.001), followed by injections (p < 0.05), dental surgeries (p < 0.010), ear
      and nose piercing (p < 0.001), and shaving (p < 0.001). Univariate analysis
      identified tattooing (p = 0.033) also as an important risk factor. CONCLUSION:
      Multiple risk factors have been identified in nearly all HCV infected patients.
      The identification of multiple risk factors of hepatitis C acquisition may have
      important implications in the approach to HCV surveillance, prevention, and
      management.

PMID- 24669628
TI  - Serum inhibin B as a diagnostic marker of male infertility.
AB  - BACKGROUND: Infertility affects about 15% of all couples in the world.
      Approximately 40% of all infertility cases could be attributed entirely to male
      factors. Serum inhibin B has emerged as a sensitive marker of male fertility.
      Analysis of serum inhibin B reflects the relationship between inhibin B, Sertoli
      cell function and spermatogenesis. METHODS: This validation study was conducted
      to calculate the sensitivity, specificity, positive and negative predictive value
      of serum inhibin B in diagnosis of male infertility, using semen analysis as the
      gold standard. One hundred and sixty men were included in the study, they
      reported for semen analysis for evaluation of male infertility. Sperm count was
      done per standard procedure. Serum inhibin B level was determined by ELISA.
      RESULTS: Serum inhibin B level > or = 80 pg/ml was regarded as a normal response.
      The serum inhibin B test had 75% sensitivity, 93.1% specificity, 80.5% PPV and
      90.7% NPV. CONCLUSION: Serum inhibin B has a positive correlation with sperm
      counts and could be used for evaluation of male infertility as a non-invasive
      predictor of spermatogenesis. The sensitivity, specificity and PPV are
      appropriate for clinical decision making and to avoid unnecessary testicular
      biopsies.

PMID- 24669627
TI  - Tendonitis: the major cause of pain in osteoarthritis knee joint.
AB  - BACKGROUND: The conventional concept of osteoarthritis is that it occurs as an
      aging and degenerative process resulting in reduction of the surface cartilage,
      narrowing of the joint space and reduction of the synovial fluid. The objective
      of this study was to introduce the new technique of unmasking and treating the
      underlying problem confirming lesions outside the knee joint being the cause of
      pain in osteoarthritic knee joint. METHODS: Clinical work making the base of this
      paper was carried out at Pain and Plegia Centre, Dabgari Gardens Peshawar from
      2005 to 2012. Patients reporting with knee pain were palpated deep around the
      knee joint and major tender spots identified upon Adductor tubercle on medial
      aspect and Gastrocnemius (lateral head) on lateral aspect proximal to the knee.
      These lesions were injected each with 20 mg of Triamcinolone Acetonide diluted in
      2 ml of Xylocaine 2%. RESULTS: The lesions responded favourably to the simple
      treatment and patients of pain knee joint of various durations were completely
      pain free. The optimum healing time of the lesions was 10 days. CONCLUSION:
      Osteoarthritic changes inside the knee joint may not be the cause of painful
      knee, rather it can be a referred pain. Two lesions, Adductor tubercle on medical
      side and lateral head of Gastrocnemius on the lateral side proximal to the knee
      joint are identified to attribute to this pain.

PMID- 24669630
TI  - Response to different conventional interferons in treatment of chronic hepatitis
      C.
AB  - BACKGROUND: Sustained virological response to interferon therapy is a great
      challenge for patients of chronic Hepatitis C. Over 20 brands of interferons are
      available in the local market with each claiming over 80% response and a wide
      variation in the cost thus creating confusion for treating physicians as to which
      drug should be selected. METHODS: Chronic Hepatitis C patients attending
      outpatients department of Pakistan Medical Research Centre JPMC from January 1998
      December 2010 were evaluated. Complete blood count, liver function tests, serum
      proteins, HCV-RNA were done in all cases before starting therapy. Side effects
      were also noted. RESULTS: Total of 851 cases received interferon 3 MIU three
      times a week for 6 months. There were 638 (75%) males and 213 (25%) females, mean
      age was 36.1 +/- 10.4 years. All were HCV-RNA positive prior to treatment, at the
      end of 6 months 666 (78.3%) became negative while 185 (21.7%) were non-responders
      with positive HCV RNA. End of treatment response (ETR) showed 84.7% with Bioferon
      (Argentina), 83.8% Hebron (Cuba), 82.2% INF (Argentina), 82.1% Ceron (China), 81%
      Viteron (Korea), 80.7% Leveron (Argentina), 81.5% Hepaferon, 79.1% Anferon
      (China), 77.4% Intron (Belgium), 75% Green alpha (Korea), 74% Roferon
      (Switzerland), 67.3% Uniferon (Lithuania), and 68.4% with others. Post-treatment
      211 cases were lost to follow-up. In remaining 358/640 (55.9%) negative for HCV
      RNA, at six months follow up, whereas 98 (15.3%) relapsed. Sustained virological
      response (SVR) Ceron 68.2%, Hebron 66.3%, Bioferon 65.2%, Leveron 60.5%, Intron
      60.3%, Viteron 57%, Anferon 53.3%, Green alpha, Roferon, Hepaferon, and others
      50%, INF 48.5% and Uniferon 41.9%. Average cost of these interferons was Rs.
      6,000/month, except Hepaferon 5,000/month, Roferon 10,600/month. CONCLUSIONS: ETR
      ranged from 74-84.7% and SVR 41.9% to 68.2% and > 60% SVR was observed with
      Ceron, Hebron, Bioferon, Leveron, Intron and were cost effective.

PMID- 24669629
TI  - Frequency and types of bodily medico-legal injuries in an urban area.
AB  - BACKGROUND: The primary objective of the study was to know the types and
      frequency of the bodily medico legal injuries in an urban setup of Abbottabad and
      compare it with that of rural, study. METHODS: Data was retrospectively collected
      by selecting 55 cases consecutively. Data of injury types was analysed. RESULTS:
      The number of injured males in this study was 44 (80.0%), while the females were
      11 (20.0%). The most common types of injuries were others (50.9% among males and
      14.5% among females). CONCLUSIONS: Our study shows relatively true picture of
      frequency and types of injuries. It was observed that male population is more
      prone to violence than females owing to the conservative life style of women in
      our societies both rural and urban.

PMID- 24669631
TI  - Maternal mortality: a ten year review in a tertiary care setup.
AB  - BACKGROUND: Maternal mortality ratio of a country is indicative of its health and
      development status. Information on maternal mortality is required to determine
      this status and to set priorities for policy making and programmatic and
      operation research strategies. This study was conducted to determine the causes
      of maternal mortality in a tertiary care hospital. METHODS: This study was
      conducted in Department of Obstetrics & Gynaecology B Unit, Ayub Medical College,
      Abbottabad, from January 2002 to January 2012. Data of all the pregnant patients
      admitted to Obs/Gyn Unit 'B' Labour Room were retrospectively collected and
      reviewed for the causes of direct maternal deaths. RESULTS: There were 21,120
      deliveries during the study period. Out of these, there were 163 maternal deaths.
      The maternal mortality ratio was calculated as 772 per 100,000 live births.
      Direct maternal deaths constituted 143 (87.7%) and indirect deaths were
      responsible for 20 (12.3%) deaths. Haemorrhage was the leading cause of maternal
      death and was responsible for 43.55% of maternal deaths, while eclampsia was
      observed in 26.99% of maternal deaths. In 6.13% of patients rupture uterus was
      the cause of maternal death. CONCLUSION: Maternal mortality in our part of the
      world is high and most of the causes of maternal death remain haemorrhage and
      eclampsia. Haemorrhage which is the leading cause of maternal death is both
      predictable and preventable, if proper peripartum care is provided, maternal
      mortality can be reduced.

PMID- 24669632
TI  - Iron status: is there a role in febrile seizures?
AB  - BACKGROUND: Febrile seizure a common convulsion disorder in children, can lead to
      increased morbidity and mortality because of risk of aspiration and hypoxia
      during prolonged febrile seizures. There are many risk factors associated with
      febrile seizures and their recurrence. We conducted this study to see if there is
      a role of iron status in febrile seizures. METHODS: This cross-sectional study
      was conducted in 323 children 6 months to 5 years of age admitted in department
      of Paediatric DHQ Hospital Faisalabad with fever and seizures from July 2009 to
      April 2011. Iron deficiency anaemia including haemoglobin concentration (Hb),
      Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH) and Plasma
      Ferritin were measured. RESULTS: Febrile seizures were more common between ages
      12 months to 36 months. Of 323 children with febrile seizures 17 (5.3%) were iron
      deficient. Mean Hb was 11.71+/- 1.38 g/dL, mean MCV 78.40 +/- 3.29, mean MCH
      27.11 +/- 3.28, and mean ferritin was 66.57 +/- 24.7. CONCLUSION: Iron deficiency
      anaemia was not common in patients with seizures. Iron status has no role in
      febrile seizures.

PMID- 24669633
TI  - Causative bacteria and antibiotic resistance in neonatal sepsis.
AB  - BACKGROUND: Neonatal sepsis is characterised by bacteraemia and clinical symptoms
      caused by microorganisms and their toxic products. Gram negative bacteria are the
      commonest causes of neonatal Sepsis. The resistance to the commonly used
      antibiotics is alarmingly high. The major reason for emerging resistance against
      antibiotics is that doctors often do not take blood cultures before starting
      antibiotics. We have carried out this study to find out various bacteria causing
      neonatal sepsis and their susceptibility to antibiotics for better management of
      neonatal sepsis. METHODS: A total of 130 neonates with sepsis who were found to
      be blood culture positive were taken in this study. Culture/sensitivity was done,
      isolated organisms identified and their sensitivity/resistance was noted against
      different antibiotics. Data were arranged in terms of frequencies and percentage.
      RESULTS: Out of 130 culture proven cases of neonatal sepsis, gram negative
      bacteria were found in 71 (54.6%) cases and gram positive bacteria in 59 (45.4%)
      cases. Staphylococcus aureus was the most common bacteria found in 35 (26.9%)
      cases followed by Escherichia coli in 30 (23.1%) cases. Acinetobacter species,
      Staphylococcus epidermidis, Klebseila, Streptococci, Enterobacter cloacae and
      Morexella species were found in 17 (13.1%), 17 (13.1%), 13 (10%), 7 (5.4%), 6
      (4.6%), and 5 (3.8%) cases respectively. In most of the cases causative organisms
      were found to be resistant to commonly used antibiotics like ampicillin,
      amoxicillin, cefotaxime, and ceftriaxone (77.7%, 81.5%, 63.1%, and 66.9%
      respectively). There was comparatively less (56.9%) resistance to ceftazidime.
      Gentamicin had resistance in 55.1% cases, while amikacin and tobramycin had
      relatively less resistance (17.4% and 34.8% cases respectively). Quinolones and
      imipenem had relatively less resistance. Vancomycin was found to be effective in
      100% cases of Staphylococcus group. CONCLUSION: Staphylococcus aureus are the
      most common gram positive bacteria and Escherichia coli are the most common gram
      negative bacteria causing neonatal sepsis. Resistance to commonly used
      antibiotics is alarmingly increasing. Continued surveillance is mandatory to
      assess the resistance pattern at a certain level.

PMID- 24669634
TI  - Risk factors for urinary bladder cancer in Baluchistan.
AB  - BACKGROUND: Urinary Bladder cancer is a life threatening and aggressive disease.
      This retrospective study was conducted in Baluchistan for assessing the risk
      factors for urinary bladder cancer. METHOD: A questionnaire was developed in
      order to collect the requisite information about the characteristics like age,
      drinking habits, smoking history, family history of cancer and others factors.
      Interview method was used to obtain the information from 50 cases and 100
      controls from two hospitals of the province. Binary logistic regression model was
      run to study the odds ratios and 95% confidence intervals. RESULTS: The odds
      ratios and 95% confidence intervals for cigarette smoking, fluid consumption and
      higher use of fruits were [26.064; 7.645-88.856], [0.161; 0.059-0.441], and
      [0.206; 0.059-0.725] respectively. CONCLUSIONS: The higher risk of urinary
      bladder cancer was observed in smokers as compared to non-smokers. Higher
      consumption of fluid and fruits are protective factors against the disease.

PMID- 24669635
TI  - Prevalence of hepatitis B and C in healthy adult males of paramilitary personnel
      in Punjab.
AB  - BACKGROUND: Global prevalence of Hepatitis B varies from high (> 8%) in Africa,
      Asia and Western Pacific to low (< 2%) in Western Europe, North America and
      Australia. An estimated 180 million people worldwide including 4 million people
      in USA are infected with HCV. This cross-sectional observational study was
      carried out at Department of Pathology, Pakistan Rangers (Punjab) Central
      Hospital, Lahore from March to June 2010 to determine prevalence of HBV and HCV
      infection among serving asymptomatic healthy adult males of paramilitary force.
      METHODS: The healthy adult males from province Punjab serving in Pakistan Rangers
      Punjab without previous history of known positivity for HBV or HCV infection were
      included in the study. Demographic data including the district of origin were
      noted. HBsAg and anti-HCV antibodies were tested by rapid immuno-chromatographic
      method while positive tests were reconfirmed by enzyme immuno-assay (EIA).
      RESULTS: Out of total 15,793 adults screened for Hepatitis B & C viral
      infections, 14,027 adults belonged to the province of Punjab. There were 396
      (2.82%) adults who were found positive for HBsAg and 511 (3.64%) positive for
      anti-HCV on screening. Retesting of the positive tests by EIA showed 396 (2.82%)
      positive for HBsAg, and 440 (3.13%) for anti-HCV respectively. Specificity of
      immune chromatographic method for HBsAg and anti-HCV calculated taking EIA as
      gold standard was 100% for HBsAg and 99.5% for anti-HCV while positive predictive
      value of the immuno-chromatographic methods was 100% for HBsAg and 86.1% for anti
      HCV. Highest of prevalence of HBsAg was seen in Rahimyar Khan (7.58%) while high
      prevalence of anti-HCV was seen in Chiniot (8.9%), Faisalabad (7.2%), Vehari
      (7.03%), Muzaffargarh (5.95%) and Sheikhupura (5.83%). CONCLUSION: Overall
      prevalence of HBsAg and anti-HCV is on the decline. The isolated pockets of very
      high prevalence of HCV infection in the districts of Chiniot, Faisalabad, Vehari,
      Sheikhupura, Rahimyar Khan, Muzaffargarh, and Okara pose a community health
      problem with a dire need to adopt strict preventive measures in the medical and
      social practices with effective public awareness campaigns.

PMID- 24669636
TI  - Demographics of basal cell carcinoma and its surgical management.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common, slow growing epidermal
      skin tumour and an increase in its incidence has been noticed in the past
      decades. Different treatment options include surgical and non-surgical measures.
      Surgical options include surgical excision, cryosurgery, curettage,
      electrodessication and Mohs micrographic surgery. Non-surgical treatments options
      are 5-flourouracil, photodynamic therapy, immunomodulation and radiotherapy. This
      study was conducted to determine the demographics of facial BCC and its rate of
      incomplete excision and recurrence. METHODS: Clinically diagnosed facial BCCs
      were included in this prospective descriptive study. Tumours were excised with 3
      5 mm clinically palpable safe margins and were sent for histopathological
      confirmation and margin clearance. All patients were followed for a minimum of
      two years to look for any recurrence. The demographic data, site, clinical
      presentation, size of the lesion, excision margins, reconstructive options,
      complications, histopathological margin clearance and recurrence was recorded and
      analysed. RESULTS: A total of 139 cases were recruited in this study. Four cases
      were lost in follow-up. Out of remaining 135 patients including 78 males and 57
      females with a mean age of 58.6 years were studied. The commonest site of
      involvement was nose (45.9%), followed by periocular (28.1%) and cheek (15.6%)
      regions. The most common clinical type was nodular (51%) followed by ulcerative
      (38.5%). In majority of the cases, the resulting defect after excision was
      reconstructed with local flaps (57.8%). Majority (77.8%) of tumours had
      histopathologically clear margins while 20% had tumour involvement. During 2
      years follow-up period, 8.9% patients had tumour recurrence.

PMID- 24669637
TI  - Needle-stick injury: a rising bio-hazard.
AB  - BACKGROUND: Needle stick injury has been identified as the foremost health allied
      concern and the specialty of dentistry is not an exception. Its incidence can be
      reduced when a dental practitioner is completely proverbial to the standard cross
      infection control measures. This study was intended to assess the knowledge,
      attitude and practices among the dental practitioners regarding Needle Stick
      Injuries and associated risk factors. METHODS: This survey was carried out in the
      Oral Surgery Department, Dr. Ishrat-ul-Ebad Khan Institute of Oral Health
      Sciences, Karachi. Dental practitioners of different job categories were
      conveniently approached by the BDS students. They all were provided with a
      structured and validated, self-administered questionnaire. Descriptive statistics
      and Chi-square test was applied with 5% level of significance. RESULTS: All 100
      (55 females and 45 males) practitioners agreed to participate in the study.
      Prevalence of Needle Stick Injury observed was 30% with no significant
      relationship with the demographic characteristics. Seventy-four percent of the
      participants were aware of the universal guidelines. Majority (88%) of the dental
      personnel believed that recapping of needles should be performed soon after use
      and 53% knew about needle-less safety devices. These injuries were experienced by
      30% of the respondents, of which just 28% were reported. CONCLUSION: Dental
      practitioners were at high risk of getting Needle Stick Injuries in dental
      offices. Most of them had knowledge about it but there was lack of practice of
      universal precautions.

PMID- 24669638
TI  - Assessment of patients' satisfaction in medical and surgical wards in a tertiary
      care hospital.
AB  - BACKGROUND: Evolution is the natural process that is not limited merely to the
      biological world but to the social world as well. The standards of living and the
      expectations change with time. This study was done to generate data that can help
      doctors and hospital administration to identify and solve problems. METHODS: It
      was a cross-sectional study conducted at a major tertiary care hospital of KPK
      through the month of July 2012. An interviewer based patient satisfaction
      questionnaire was used to estimate patients' satisfaction by asking questions
      regarding admission procedure, referral, clinical and lab investigation services,
      attitude of doctors and nurses, nursing services, cleanliness condition of the
      wards and overall level of satisfaction. RESULTS: Study included 305 patients,
      205 from surgical wards (144 males, 61 females) and 100 from Medical wards (52
      males, 48 female). Satisfaction level was high among females than males. Most of
      the patients having low level of education and unemployed patients were
      satisfied. Cleanliness condition of wards and bathrooms was highly criticised.
      Attitude of doctors and nurses was much appreciated. About 70% of the patients
      were satisfied with explanation regarding their disease. More than half (59%)
      were not aware of post-surgical complications, and 67% were not aware of the use
      and possible side-effects of medication. About half of the patients couldn't
      utilise hospital lab. Overall satisfaction level was 68% in medical wards and 77%
      in surgical wards. CONCLUSIONS: Overall level of satisfaction was fair in both
      wards. Attitude of doctors and nursing staff was appreciated, but cleanliness
      conditions were criticised. There is a need for availability of free medicine and
      improvement of laboratory services and cleanliness.

PMID- 24669639
TI  - Frequency of placenta previa in women with history of previous caesarean and
      normal vaginal deliveries.
AB  - BACKGROUND: Placenta previa is known to be associated with previous caesarean
      deliveries, advanced maternal age, increasing parity, smoking, curettage and
      myomectomy. This study was carried out to compare the frequency of placenta
      previa, in women with previous caesareans versus those with normal vaginal
      deliveries. METHODS: It was one year study conducted at the Department of
      Obstetrics and Gynaecology Unit B, Ayub Teaching Hospital, Abbottabad. One
      hundred women were included in the study, 50 in Group A with previous caesarean
      deliveries, and 50 in Group B with previous normal vaginal deliveries. Frequency
      of placenta previa in both groups was analysed. RESULTS: Placenta previa was
      found in one (2%) woman in Group A, and in two women (4%) in Group B. It was not
      found in para 4 or less in both groups. One woman in Group A and two women in
      Group B with parity 4 or more had placenta previa (p < 0.05). None of the women
      with previous one scar had placenta previa, while with previous 2 scars one had
      placenta previa (p < 0.05). One woman with placenta previa in Group A and both
      women with placenta previa in Group B were more than 25 years old. Placenta
      previa was not found in women below 25 years of age. CONCLUSION: Previous one
      caesarean section did not increase the frequency of placenta previa. Increasing
      number of scars, increasing maternal age beyond 25 years and increasing parity
      beyond 4 were associated with placenta previa.

PMID- 24669640
TI  - Septic/unsafe abortion: a preventable tragedy.
AB  - BACKGROUND: Unsafe abortion is one of the greatest neglected problems of health
      care in developing countries like Pakistan. In countries where abortions are
      restricted women have to resort to clandestine interventions to have an unwanted
      pregnancy terminated. The study was conducted to find out the prevalence of
      septic induced abortion and the associated morbidity and mortality and to
      highlight the measures to reduce it. METHODS: This cross-sectional descriptive
      study was carried out in Obs/Gyn B Unit, Ayub Teaching Hospital, Abbottabad from
      January 2007 to December 2011. During this period all the patients presenting
      with pyrexia lower abdominal pain, vaginal bleeding, acute abdomen, septic or
      hypovolaemic shock after undergoing some sort of intervention for abortion
      outside the hospital were included. After thorough history, examination and
      detailed investigations including high vaginal and endocervical swabs for culture
      and sensitivity and pelvic ultrasound supportive management was given followed by
      antibiotics, surgical evacuation of uterus/ major laparotomy in collaboration
      with surgeon as required. Patients with DIC or multiple system involvement were
      managed in High Dependency Unit (HDU) by multidisciplinary team. RESULTS: During
      the study period out of a total 6,906 admissions 968 presented with spontaneous
      abortion. There were 110 cases (11.36%) of unsafe abortion, 56.4% presented with
      vaginal discharge, 34.5% with vaginal bleeding, 21.8% with acute abdomen, while
      18.9% in shock and 6.8% with DIC. Forty-nine percent patients used termination as
      a method of contraception. Mortality rate was 16.36%, leading cause being
      septicaemia. CONCLUSION: Death and severe morbidity from unsafe abortions and its
      complications is avoidable through health education, effective contraception,
      early informed recognition and management of the problem once it occurs.

PMID- 24669641
TI  - Comparison of FNA vs surface swab culture in isolating core flora in recurrent
      tonsillitis.
AB  - BACKGROUND: Tonsillitis is one of the most common childhood afflictions. This
      prospective study was designed to explore the possible role of fine needle
      aspiration of recurrently inflamed tonsils in determining their core flora.
      RESULTS: Seventy-seven patients at DHQ Hospital Haripur undergoing tonsillectomy
      for recurrent tonsillitis were included in the study. Colonies grown from fine
      needle aspirate and surface swab were compared with tonsillar core culture
      obtained after tonsillectomy. The pathogens isolated by fine needle aspiration
      culture were not greatly different from surface swab results in comparison to
      core isolates. CONCLUSION: The results of fine needle aspirate do not appear to
      confer any advantage over surface swab in representing core flora. These findings
      indicate no preferred clinical use for fine needle aspiration in the management
      of recurrent tonsillitis.

PMID- 24669642
TI  - 'Student Lady Health Visitors': their stress profile and willingness to practice.
AB  - BACKGROUND: Lack of Reproductive health facilities including high maternal and
      neonatal mortality is a major problem of our region. Skilled healthcare providers
      like Lady Health Visitors can play a significant role in improving parameters of
      reproductive healthcare. The objectives of this study were to assess stress
      profiles in student lady health visitors and their willingness to practice in
      future. METHODS: Cross sectional survey conducted at two public health schools in
      District Peshawar with student Lady Health Visitors as study participants.
      RESULTS: Majority (64.4%) of respondents were satisfied with their choice of
      career, 78% thought they had adequate knowledge to practice independently, 47.7%
      thought that their life in this profession will be stressful. Most of them were
      facing financial difficulties during their course, 84.8% enjoyed support of their
      family in choice of career, 50-82% reported psychosomatic problems arising as
      result of stress in their lives. CONCLUSION: Most of the respondents were happy
      with their choice of profession and were willing to practice in future. High
      prevalence of stress in lives of respondents warrants counselling services by
      institutions.

PMID- 24669643
TI  - Isolation of medical students: communication barrier and its effect on career.
AB  - BACKGROUND: Communication barriers affect student-student interaction and student
      patient interaction. This study is aimed at exploring the social, cultural and
      academic spheres where medical students feel getting isolated. METHOD:
      Questionnaire based cross-sectional survey was undertaken at Ayub Medical
      College, Abbottabad in the month of July, 2013. Cluster sampling technique was
      employed. RESULTS: Linguistic problems in the college greatly affected medical
      students. Female medical student are comparatively more affected. These problems
      were less common in 1st year and most common in 3rd year where clinical classes
      are started. There are distinct gender based problems in communicating among male
      and female student with as many as 37.2% reported feeling difficulty in
      communicating with students of opposite gender. However this difficulty in
      communication gradually faded on proceeding from 1st year towards final year.
      About frank interaction with opposite gender, 65.9% students felt that society
      had negative impact upon it. While communicating with patients of opposite
      gender, almost a quarter of students (27.3%) reported facing difficulties, 56.9%
      students reported to have abject apathy towards the colleagues of opposite
      gender. CONCLUSION: Linguistic issues, gender discrimination, negative impact of
      society and lack of concern for fellow colleagues is affecting student-student
      interaction and student-patient interaction. There is need to create student
      friendly environment.

PMID- 24669644
TI  - Frequency of conversion to overt hypothyroidism in patients with and without
      subclinical hypothyroidism.
AB  - BACKGROUND: Sub-clinical hypothyroidism (SCO) poses diagnostic and management
      difficulties for pathologists and clinicians. Cases of SCO are now diagnosed with
      increasing frequencies worldwide mainly because of availability of more sensitive
      methods for serum TSH, total T3 and free T4 assays. The rate of progression of
      SCO to overt hypothyroidism varies in different populations. Sub-clinical
      hypothyroidism has been suggested as a risk factor for hypothyroid complications.
      There is a need to identify and treat patients with SCO before they convert to
      overt hypothyroidism and develop complications. Objective was to compare the
      development of overt hypothyroidism in a cohort of patients of sub-clinical
      hypothyroidism and in subjects with normal thyroid function tests. METHODS: It
      was Cohort study conducted at Department of Chemical Pathology and Endocrinology,
      Armed Forces Institute of Pathology, Rawalpindi. Hundred patients of SCO and
      almost equal number of age and sex-matched subjects with normal Thyroid function
      test (TFT) were enrolled as healthy controls. Subclinical hypothyroid patients
      and controls were followed for a period of one year on six monthly bases. The
      patients were examined for signs and symptoms of hypothyroidism and serum TSH,
      total T3 and free T4 were estimated. The clinical history, physical examination
      and thyroid function tests were recorded on the pre-designed Performa. RESULTS:
      Fourteen (14%) out of 100 cases of the SCO patients developed overt
      hypothyroidism, SCO had 2.8 times more risk for conversion to overt
      hypothyroidism as compared to healthy controls. Moreover female gender and
      initial levels of serum TSH were the most important predictors for conversion of
      SCO to overt hypothyroidism. CONCLUSION: The frequency of conversion to overt
      hypothyroidism in SCO patients approaches 14% and was more commonly observed in
      female patients.

PMID- 24669645
TI  - Anxiety and depression in doctors undergoing postgraduate training courses at
      Armed Forces Postgraduate Medical Institute Rawalpindi.
AB  - BACKGROUND: In the recent past doctors own physical and mental health care has
      been a focus of research worldwide. The estimated suicide rate among doctors is
      approximately one per day. Various other studies reveal high scores of anxiety,
      depression, job dissatisfaction and burnouts. The study was carried out to
      determine the prevalence of anxiety and depression in doctors undergoing various
      postgraduate training courses at AFPGMI, Rawalpindi. METHODS: This cross
      sectional study was carried out from June to December 2010 at Armed Forces
      Postgraduate Medical Institute, Rawalpindi. All willing available trainee doctors
      were included in the study. Urdu version of Beck's anxiety and depression scale
      was used. RESULTS: Average anxiety score of all docctors was (8.05). The anxiety
      score was 15.7 in ENT, 12.0 in Pathology, 8.5 in Medicine, 7 in Basic Medical
      Siciences, 5.7 in Ophthalmology, 3.61 in Surgery, 3.3 in Radiology, and 3.05 in
      General Duty Medical Officers. With overall average score of (9.2), the average
      score on depression was highest in Anaesthesiology (20), followed by Radiology
      (10.05), Pathology (10.02), Basic Medical Sciences (9) Ophthalmology (8.2),
      Medicine (7),and General Duty Medical Officers (4.1). CONCLUSION: This study
      reveals an important area of doctors' own health which remains relatively
      neglected. Rectification measures are required to reduce anxiety/depression, and
      mortality and morbidity among doctors.

PMID- 24669646
TI  - Oral clonidine for attenuation of haemodynamic response to laryngoscopy and
      endotracheal intubation in known hypertensive patients.
AB  - BACKGROUND: Sympathetic response associated with laryngoscopy and endotracheal
      intubation is recognised as a potential cause for a number of complications
      especially in hypertensive patients. Various methods have been used to attenuate
      these haemodynamic responses; however most of the studies are in normotensive
      patients. The aim of our study was to compare the effect of oral clonidine and
      1/V fentanyl with oral placebo and I/V fentanyl in attenuating the haemodynamic
      responses to laryngoscopy and intubation in known hypertensive patients. METHOD:
      In a double blind randomised controlled trial. 60 hypertensive patients, taking
      antihypertensive drugs and with systolic blood pressure below 160 (mmHg and
      diastolic blood pressure below 100 mmHg scheduled for elective surgeries,
      requiring oral endotracheal intubation and age ranging from 40-65 years were
      included in this study and randomly divided into Group A (clonidine 0.2 mg +
      fentanyl 2 microg/Kg) and Group B (Placebo + fentanyl 2 microg/Kg). RESULTS:
      Demographic data were comparable in both groups. There were no statistically
      significant differences between the two groups in the duration of laryngoscopy
      and intubation. There was statistically significant attenuation in heart rate in
      both groups (p = 0.020). The trends of attenuation of systolic blood pressure,
      diastolic blood pressure and mean arterial pressure in Group A compared to Group
      B, were statistically significant (p = 0.034, 0.011, 0.011 respectively).
      CONCLUSION: Clonidine, under the present study design attenuates the haemodynamic
      response to laryngoscopy and endotracheal intubation in known hypertensive
      patients.

PMID- 24669647
TI  - Phagocyte functions of human subjects living in high level of natural radiation
      areas in Iran.
AB  - BACKGROUND: Iran is considered as one of the countries which are located in high
      radiation area. Ramssar contains natural radioactive sources (Uranium-238) that
      can produce Radium-226 with high solubility and Radon gas with ability to fuse in
      dirt, soil, and water in its decay chain. Radioactive rays can produce free
      radicals with a short life time but high energy, which lead to changes structures
      of protein bindings, hormones activity, lipids oxidation and DNA breakage which
      can induce autoimmune diseases and other disorders. The aim of this study was to
      evaluate effects of natural radiation on innate and humoral immune response of
      those exposed to natural radioactive rays compared to control group. METHODS:
      Subjects from high and low natural radiation areas were included in the study.
      Neutrophil chemotaxis, Nitro-Blue Tetrazolium (NBT), and antioxidant effects were
      evaluated for effects of radioactivity on free radicals and innate immunity. Also
      Cytokines (IL-2, IL-4) levels for humoral immune system of the subjects were
      measured. RESULTS: Total plasma antioxidant level and potency of respiratory
      burst in individuals who lived in area with high levels of natural radiation
      decreased significantly compared with, control subjects who lived in the other
      areas of Ramssar with normal radiation. The level of IL-4 increased in
      individuals who lived in area with high levels of natural radiation, which could
      lead to Th2 pattern of immune response whether neutrophils chemotaxis in the
      groups living in the area with high level of natural radiation didn't change
      significantly when compared to control. CONCLUSION: Neutrophil respiratory burst
      activities suggested that NADPH probably reduced due to different reasons
      including decrease in NADPH oxidase and other enzymes, and mutation of the genes
      or production of oxidant substances. Neutrophil chemotaxis reduced but this
      reduction was not statistically significant.

PMID- 24669648
TI  - Validation of tuning fork test in stress fractures and its comparison with
      radionuclide bone scan.
AB  - BACKGROUND: Stress fractures are quite common both in athletes and military
      recruits. The purpose of the study was to evaluate the efficacy of tuning fork in
      stress fractures by comparing it with three phase bone scan. METHODS: The current
      study examined 55 subjects whose age ranged 18-28 years. X-rays of all the
      subjects were unremarkable. After history and clinical examination tuning fork
      test (TFT) was performed on each case by placing 128 Hertz vibrating tuning fork
      on the site of pain (underlying bony surface) of tibia or fibula. Each case was
      scanned using triple phase bone scintigraphy. RESULTS: Fifty-five patients had a
      total of 67 stress fractures, out of which 53 were picked up by TFT. Sensitivity
      of TFT was found to be 79% and specificity of 63%. Positive and negative
      predictive values were 88% and 46% respectively. CONCLUSION: Tuning fork test is
      a simple and easy approach of diagnosing stress fractures which can be performed
      even by athletics and military trainers. Management should be initiated in
      patients who have history of stress related below-knee pain and positive tuning
      fork test without waiting for bone scintigraphy. For complicated cases the bone
      scan is the gold standard for diagnosis.

PMID- 24669649
TI  - Removal of coins from oesophagus with Foley catheter under ketamine effect.
AB  - BACKGROUND: Foreign body ingestion continues to be a common problem that
      contributes significantly to high morbidity and mortality worldwide. Coins are
      the most common foreign body lodged in the oesophagus. This study was conducted
      to describe our experience of removal of coins from oesophagus with Foley
      catheter under ketamine effect. METHODS: This was a retrospective study conducted
      at District Head Quarter Hospital, Buner. Foley's catheter was used to remove the
      coins under ketamine effect. RESULTS: Coins were successfully removed from 188
      children without complications. Amongst these children 101 (53.72%) were male and
      87 (46.28%) were female. The mean age of these children was 3.79 years. The coin
      was removed in first attempt in 154 (81.91%) cases. In 34 (18.08%) cases more
      than one attempts were required. The mean time for the removal of coin (i.e.,
      initiation of catheter to removal of coin) was 55.30 seconds. The most commonly
      ingested coin was a one rupee coin (139, 73.93%), followed by two rupee coin (47,
      25%), and 5 rupee coin (2, 1.06%). CONCLUSION: The coin impacted at the
      cricopharyngeus or upper oesophagus can be safely, easily, and quickly removed by
      Foley catheter under ketamine effect.

PMID- 24669650
TI  - Association of leptin with type 2 diabetes in non-obese subjects.
AB  - BACKGROUND: South Asians have a high tendency to develop type 2 diabetes even at
      low BMI. We evaluated serum leptin levels in a group of non-obese type 2
      diabetics. METHODS: An observational study conducted on 90 subjects, 55 with Type
      2 diabetes mellitus, and 35 normal controls (non-diabetics). BMI, waist
      circumference, serum leptin, and serum glucose were measured. The correlation
      between these variables was studied by multiple regression analysis. RESULTS:
      Serum leptin levels were positively correlated with BMI in obese (r = 0.976) and
      non-obese diabetics (r = 0.956). Serum leptin was related with diabetes (r = 
      0.153, p = 0.001). Serum leptin was highly correlated with waist circumference in
      obese than non-obese diabetics, (r = 0.753). Mean serum leptin level was 21.4
      etag/ml in non-obese diabetics and 34.9 etag/ml in diabetic group. It is even
      lower than the non-obese, non-diabetics (23.3 etag/ml). Multivariate linear
      regression analysis between leptin and age, weight, BMI, waist circumference in
      patients shows only a strong association with BMI in diabetics (p = 0.0001),
      while in non-diabetic it was not significant (p = 0.07). Serum leptin was high in
      diabetics taking oral hypoglycaemic (37.8 +/- 19.1 etag/ml), while it was low in
      diabetics taking insulin injections (29.3 +/- 24.2 etag/ml). CONCLUSION: Low
      leptin levels are associated with type 2 diabetes mellitus independent of changes
      in BMI.

PMID- 24669651
TI  - Obstetrical referrals by traditional birth attendants.
AB  - BACKGROUND: In Pakistan 90% of births are conducted by TBA's. In most cases,
      TBA's are unable to diagnose the complications and are often unable to take
      decisions on timely referral. The objective of this study was to determine the
      prevalence, nature and outcome of life threatening obstetrical conditions in
      referrals by Traditional Birth Attendants (TBAs). METHODS: This Observational,
      Descriptive study was conducted from January to December 2007, in the obstetrical
      unit of Fatima Hospital, Baqai Medical University, a tertiary care community
      based hospital. The study included patients referred by TBA's who developed life
      threatening obstetric conditions (LTOCs). RESULTS: Total 64 patients were
      referred by TBA's. The prevalence was 7.8%. Out of them, 53 (82.8%) patients
      admitted with life threatening obstetric conditions. The near-miss morbidities
      and mortalities were 45 (84.9%) and 8 (15%) respectively. Maternal mortality to
      Near-miss morbidity ratio was 1:6. Obstructed labour caused near-miss morbidity
      in 32 (60.3%) patients with no mortality. Postpartum haemorrhage as life
      threatening condition developed in 16 (30.1%) patients with 10 (18.8%) near-miss
      morbidities and 6 (11.3%) mortalities. Puerperal sepsis accounted for 1 (1.88%)
      near-miss morbidity and 2 (3.76%) mortalities. The mortality index for puerperal
      sepsis is (66.6%) almost double of postpartum haemorrhage (37.5%). CONCLUSION:
      Mortality to near miss morbidity ratio is high. Misidentification and late
      referrals of complicated cases by TBA's were responsible for near-miss
      morbidities and mortalities.

PMID- 24669652
TI  - Paradigm in aetiology and management of zygomatic complex fractures in Pakistan.
AB  - OBJECTIVE: The purpose of this study was to compare the outcome of wire
      osteosynthesis with bone plating in the management of zygomatic complex (ZMC)
      fractures. The rationale was to enable the oral and maxillofacial surgeon to
      select either of the treatment procedure with confidence. METHODS: In this quasi
      experimental study, Sixty five patients of ZMC fractures were randomly allocated
      in groups of bone plating and wire osteosynthesis. This was done through envelope
      draw method. Three points fixation with either of the treatment modality was
      undertaken. Titanium bone plating or stain less steel wire osteosynthesis was
      carried out at frontozygomatic suture, infra orbital rim and at
      zygomaticomaxillary buttress. RESULTS: In this quasi experimental study, three
      patients failed to follow up. There were 31 patients in each group. Infra orbital
      step defect was observed in one patient of wire osteosynthesis and two patients
      of bone plating. Mild facial deformity was observed in two patients of wire
      osteosynthesis while none in that of bone plating. CONCLUSION: There is
      insignificant difference of proportion of infra orbital step defect and facial
      deformity between wire osteosynthesis and bone plating.

PMID- 24669653
TI  - Frequency and prevention of laparoscopic port site infection.
AB  - BACKGROUND: The present study was conducted to evaluate the usefulness and safety
      of the nonpowder surgical glove for extraction of the gallbladder in laparoscopic
      cholecystectomy. METHODS: The study was carried out in Capital Hospital Islamabad
      and in a private hospital. The duration of study was from March 2009 to March
      2012. This was an observational study carried out in 492 patients who underwent
      laparoscopic cholecystectomy using the surgical glove for extraction of the
      gallbladder and compared with the conventional method of gall bladder removal in
      two hospitals were analyzed. The operative findings, port site infection and co
      morbid conditions were evaluated. RESULTS: Postoperative wound infection was
      found in 27 (5.48%) of 492 cases. Umbilical port infection was found in 26
      (5.28%) of cases in which gall bladder was removed without endogloves and only
      one case (0.2%) had infection when gall bladder was removed with the endogloves.
      Wound infection was more in acute cholecystitis (25.9%) and empyema of Gall
      Bladder (44.4%). Among the co morbid conditions, diabetes mellitus has got higher
      frequency of wound infection (44%). CONCLUSION: The use of the surgical glove for
      extraction of the gallbladder is safe, cheap, simple and potentially reduces
      significant morbidity. Its routine use at laparoscopic cholecystectomy is
      mandatory in all cases.

PMID- 24669654
TI  - Assessment of carotid artery intima media thickness in hypertensive patients
      compared with normotensives by B-mode ultrasonography.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality and
      morbidity worldwide. Common carotid artery intima media thickness has recently
      generated considerable interest as a marker of atherosclerosis and in the
      prediction of clinical coronary events and coronary artery disease.
      Ultrasonography is a non-invasive technique of measuring carotid artery intima
      media thickness. This study was carried out at Military Hospital Rawalpindi
      during 6 months from 24th May to 24th Nov 2007 to compare the common carotid
      artery intima media thickness in hypertensive patients with normotensives.
      METHODS: Two hundred willing cases fulfilling inclusion criteria were included in
      the study and 200 controls were selected reporting to radiology department. Blood
      pressure was measured from brachial artery with mercury sphygmomanometer taking
      first and fifth Korotkoff sounds to identify systolic and diastolic values
      respectively. Intima media thickness was assessed in the distal part, 0.5-1.0 Cm
      proximal to carotid bulb of common carotid artery. RESULTS: The age range of
      control group was 42-85 years and of hypertensive was 41-90 years. Mean age of
      control group was 55.03 +/- 8.57 years, and of hypertensive group was 58.02 +/-
      9.74 years. The Mean of IMT right CCA of control group was 0.515 +/- 0.148 mm and
      of hypertensive group it was 1.06 +/- 0.23 mm (p < 0.001). The Mean of IMT of
      left CCA control group was 0.508 +/- 0.150 mm and of hypertensive group was 1.06
      +/- 0.223 mm (p < 0.01). CONCLUSION: Intima media thickness was significantly
      increased among hypertensive patients as compared to normotensives.

PMID- 24669655
TI  - Uses and effects of mercury in medicine and dentistry.
AB  - Mercury is known to be a toxic material with adverse effects on the body as
      claimed by so many researchers and always projected a negative aspect of this
      element. It is true that it may cause a several problems when it exceeds the safe
      limit but along with its negative image, mercury has been playing a positive role
      in the field of medicine and dentistry. It has many therapeutic uses including
      various medications, ointments, dental fillings, contact lens, cosmetics, paints
      as well as in different instruments like thermometer and sphygmomanometers.
      Mercury and its compounds used in dental practice may be responsible for release
      of mercury into the oral cavity. Compounds of mercury tend to be much more toxic
      than the element itself, and organic compounds of mercury (e.g., dimethyl
      mercury) are often extremely toxic and may be responsible in causing brain and
      liver damage.

PMID- 24669656
TI  - Olfactory neuroblastoma presenting as bleeding polyp.
AB  - Malignant tumours of the nasal cavity are rare. Olfactory neuroblastomas
      (esthesioneuroblastomas) account for only 6% of these neoplasms. Fewer than 1,000
      cases have been reported in the literature since this tumour was first described
      more than 75 years ago. A 13 year old girl presented with bleeding nasal polyp to
      ENT Department. She was operated as there were no signs of tumour the
      histopathology report revealed it to be olfactory neuroblastoma. As there was no
      intracranial extension she was given postoperative radiotherapy.

PMID- 24669657
TI  - Peripheral ossifying fibroma of oral cavity: histopathologic differential
      diagnoses.
AB  - Peripheral ossifying fibroma is a benign neoplasm that usuallydevelops from
      gingiva, presenting as an exophytic smooth surfaced pink or red nodular mass that
      is sessile or is less frequently seen on a pedicle. From the Indian perspective,
      it is usually noticed in 5th-6th decades of life with female predilection.
      Microscopically, the tumour shows stratified squamous epithelium and highly
      cellular fibrous stroma, sparse endothelial proliferation with fibroblasts and
      dystrophic calcifications. It has to be differentiated histopathologically from
      pyogenic granuloma, fibroma, peripheral giant cell granuloma, peripheral
      odontogenic fibroma and fibrous hyperplasia. A case of peripheral ossifying
      fibroma of maxillary gingiva in a 55-year-old Indian woman is reported.

PMID- 24669658
TI  - Successful enucleation of retroperitoneal cyst.
AB  - Retroperitoneal mesenteric cyst is a rare entity among the other mesenteric cysts
      and intra-abdominal tumours. A 42-year-old woman reported with pain abdomen off
      and on since one month. There were no other complaints. On ultrasonography a
      mesenteric cyst was diagnosed. Surgery was planned which revealed a
      retroperitoneal mesenteric cyst. Enucleation of the cyst was done. In follow-up
      of 6 months patient is asymptomatic. We are reporting a rarely reported
      retroperitoneal mesenteric cyst in the mesentery of the descending colon or
      sigmoid.

PMID- 24669659
TI  - Peritoneal encapsulation presenting as small bowel obstruction in a 16 year old
      girl.
AB  - Peritoneal encapsulation is a rare congenital anomaly characterized by a thin
      membrane of peritoneum encasing the small bowel to form an accessory peritoneal
      sac. Cases usually present with small bowel obstruction or can be an incidental
      finding during laparotomy. We report a case of peritoneal encapsulation
      presenting as a small bowel obstruction in a 16 year old girl. The sac was easily
      excised and surgery was otherwise uneventful. A discussion of the case and review
      of literature is presented.

PMID- 24669660
TI  - Unexpected outcome after partial epididymectomy for chronic testicular pain.
AB  - Cancer of the testis is uncommon in young males. It can present in unusual ways.
      We are presenting a case of testicular cancer presenting as an epididymal lesion
      that was diagnosed after epididymectomy.

PMID- 24669661
TI  - Misconceptions in students: how to resolve them?

PMID- 24669662
TI  - Peptide: N- glycanase is expressed in prestalk cells and plays a role in the
      differentiation of prespore cells during development of Dictyostelium discoideum.
AB  - Peptide: N-glycanase (PNGase) enzyme is found throughout eukaryotes and plays an
      important role in the misfolded glycoprotein degradation pathway. This
      communication reports the expression patterns of the pngase transcript (as
      studied by the analysis of beta-galactosidase reporter driven by the putative
      pngase promoter) and protein (as studied by the analysis of beta-galactosidase
      reporter expressed under the putative pngase promoter as a fusion with the pngase
      ORF) during development and further elucidated the developmental defects of the
      cells lacking PNGase (png(-)). The results show that the DdPNGase is an essential
      protein expressed throughout development and beta-galactosidase activity was
      present in the anterior part of the slug. In structures derived from a null
      mutant for pngase, the prestalk A and AO patterning was expanded and covered a
      large section of the prespore region of the slugs. When developed as chimeras
      with wild type, the png(-) cells preferentially populate the prestalk/stalk
      region. When the mutants were mixed in higher ratios, they also tend to form the
      prespore/spore cells. The results emphasize that the DdPNGase has an essential
      role during development and the mutants have defects in a system that changes the
      physiological dynamics in the prespore cells. DdPNGase play a role in development
      both during aggregation and in the differentiation of prespore cells.

PMID- 24669663
TI  - Protective effect of alcoholic extract of Entada pursaetha DC. against CCl4
      induced hepatotoxicity in rats.
AB  - The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body
      weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg
      body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose
      dependent hepatoprotective effect comparable to standard drug silymarin, by
      preventing increase in serum levels of alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, total protein, and total bilirubin,
      lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate
      nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes,
      superoxide dismutase, catalase and increasing reduced glutathione levels in
      liver, which suggests the antioxidant property of PSE. Histopathological studies
      also supported the above biochemical parameters. The results suggested that
      alcoholic extract of E. pursaetha possesses significant hepatoprotective activity
      in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated
      through its antioxidant activities.

PMID- 24669664
TI  - Antiarthritic activity of Cynodon dactylon (L.) Pers.
AB  - Cynodon dactylon (L.) (Poaceae) is traditionally used herb to treat fevers, skin
      diseases and rheumatic affections. The ethanolic extract of C. dactylon was found
      to be safe at all the dose levels (100, 200 and 400 mg/kg, orally) and there was
      no mortality up to the dose of 5000 mg/kg of extract when administered orally. C.
      dactylon showed significant antiarthritic activity against Freund's complete
      adjuvant induced arthritis in rats. Treatment with C. dactylon significantly
      reduced the mean percentage change in injected and non injected paw, ankle
      diameter, clinical severity and significantly increased body weight. Results were
      confirmed using biochemical parameters; there was a significant improvement in
      the levels of Hb and RBC in C. dactylon treated rats. The increased levels of
      WBC, ESR, C- reactive protein (CRP) and TNFalpha were significantly suppressed in
      C. dactylon treated rats. C. dactylon showed protective effect in arthritic
      joints but it has been supported by an improvement in bone lesions rather than in
      cartilage lesions. It can be concluded that ethanolic extract of C. dactylon at a
      dose of 400 mg/kg is effective in improving haematological level, CRP and
      reducing TNFalpha level. Phytochemical screening showed the presence of
      alkaloids, flavonoids and glycosides in ethanolic extract. All the above results
      support the traditional uses of the plant in the treatment of rheumatoid
      arthritis.

PMID- 24669665
TI  - Structural and functional analysis of cathepsin S of Heterodera spp: a promising
      candidate for its control.
AB  - Cysteine proteinases are required for a wide range of physiological processes in
      all living organisms. In parasitic nematodes, they are particularly crucial for
      the digestion of host tissues and evasion of host immune responses. Therefore, in
      general, these are identified as primary targets for the control of parasitic
      nematodes. Herein, cathepsin S-like cysteine proteinase of Heterodera avenae
      (Hacp-s) has been cloned and analysed for the first time. The predicted protein
      is 298 amino acids long and showed significant similarity with cathepsin S of
      Heterodera glycines (Hgcp-s). The sequence of cathepsin S contains a signal
      peptide of 30 amino acids which suggests its role in extracellular functions.
      Multiple sequence alignment revealed the presence of ERFNIN motif and conserved
      catalytic residues. Three dimensional structure (3D) of Hgcp-s was modelled using
      homology modelling. In order to illustrate the plausible mode of interaction of
      cathepsin S (Hgcp-s), docking analysis was performed with E-64 cysteine
      proteinase inhibitor. Docking studies revealed the hydrogen bonding of E-64 with
      Gln153, His299 and Gly203 as well as close interaction with catalytic residues
      Cys159 and Asn320 Expression analysis of Hacp-s using qRT-PCR showed high
      expression of cathepsin S in pre parasitic J2s and female stages suggesting its
      significant role in both pre-parasitic and parasitic stages of the nematode life
      cycle.

PMID- 24669666
TI  - Norethindrone-induced masculinization and progeny testing in guppy, Poecilia
      reticulata (Peters 1859).
AB  - Norethindrone(NE) was evaluated for its efficacy on alteration of sex ratio of P.
      reticulata. Either the young fry or the brooders and the resultant fry were fed a
      commercial diet incorporated with NE at 0, 25, 50, 75 and 100 mg kg(-1) diet
      (ppm) for 30-40 d in rectangular glass aquaria; this was followed by 40-60 d
      rearing on NE-free diet in out-door concrete tanks. In general, the androgen
      treatment altered sex ratio, leading to the production of a dose dependent
      increase in the percentage of males. The oral administration of the steroid at 75
      ppm for 40 d or 100 ppmfor 30 or 40 d to first feeding fry, yielded 100% males.
      On the other hand, NE administration to brooders before parturition and the
      resultant fry also produced an all-male population of guppy. The sex ratio of the
      untreated control was almost 1:1. The survival of fish in all the trials was
      high, ranging between 67 and 100%. Mating masculinized males ("XX" male) with
      normal female resulted in an all-female progeny, while crossing normal male (XY)
      from treatment groups with normal female sired normal sex ratio (1:1),
      elucidating XX-XY sex determination system in the guppy.

PMID- 24669667
TI  - Response of aerobic rice to Piriformospora indica.
AB  - Rice cultivation under aerobic condition not only saves water but also opens up a
      splendid scope for effective application of beneficial root symbionts in rice
      crop unlike conventional puddled rice cultivation where water logged condition
      acts as constraint for easy proliferation of various beneficial soil
      microorganisms like arbuscular mycorrhizal (AM) fungi. Keeping these in view, an
      in silico investigation were carried out to explore the interaction of hydrogen
      phosphate with phosphate transporter protein (PTP) from P. indica. This was
      followed by greenhouse investigation to study the response of aerobic rice to
      Glomusfasciculatum, a conventional P biofertilizer and P. indica, an alternative
      to AM fungi. Computational studies using ClustalW tool revealed several conserved
      motifs between the phosphate transporters from Piriformospora indica and 8 other
      Glomus species. The 3D model of PTP from P. indica resembling "Mayan temple" was
      successfully docked onto hydrogen phosphate, indicating the affinity of this
      protein for inorganic phosphorus. Greenhouse studies revealed inoculation of
      aerobic rice either with P. indica, G. fasciculatum or both significantly
      enhanced the plant growth, biomass and yield with higher NPK, chlorophyll and
      sugar compared to uninoculated ones, P. indica inoculated plants being superior.
      A significantly enhanced activity of acid phosphatase and alkaline phosphatase
      were noticed in the rhizosphere soil of rice plants inoculated either with P.
      indica, G. fasciculatum or both, contributing to higher P uptake. Further,
      inoculation of aerobic rice plants with P. indica proved to be a better choice as
      a potential biofertilizer over mycorrhiza.

PMID- 24669668
TI  - Phenylpropanoid enzymes, phenolic polymers and metabolites as chemical defenses
      to infection of Pratylenchus coffeae in roots of resistant and susceptible
      bananas (Musa spp.).
AB  - Activity differences of the first (phenylalanine ammonia lyase, PAL) and the last
      (cinnamyl alcohol dehydrogenase, CAD) enzymes of phenylpropanoid pathway in the
      roots of resistant (Yangambi Km5 and Anaikomban) and susceptible (Nendran and
      Robusta) banana cultivars caused by root lesion nematode, Pratylenchus coffeae,
      were investigated. Also, the accumulation of phenolics and deposition of lignin
      polymers in cell walls in relation to resistance of the banana cultivars to the
      nematode were analyzed. Compared to the susceptible cultivars, the resistant
      cultivars had constitutively significantly higher PAL activity and total soluble
      and cell wall-bound phenolics than in susceptible cultivars. The resistant
      cultivars responded strongly to the infection of the nematode by induction of
      several-time higher PAL and CAD enzymes activities, soluble and wall-bound
      phenolics and enrichment of lignin polymers in cell wall and these biochemical
      parameters reached maximum at 7th day postinoculation. In addition, profiles of
      phenolic acid metabolites in roots of Yangambi Km5 and Nendran were analyzed by
      HPLC to ascertain the underlying biochemical mechanism of bananas resistance to
      the nematode. Identification and quantification of soluble and cell wall-bound
      phenolic acids showed six metabolites and only quantitative, no qualitative,
      differences occurred between the resistant and susceptible cvs. and between
      constitutive and induced contents. A very prominent increase of p-coumaric,
      ferulic and sinapic acids, which are precursors of monolignols of lignin, in
      resistant cv. was found. These constitutive and induced biochemical alterations
      are definitely the chemical defenses of resistant cvs. to the nematode infection.

PMID- 24669669
TI  - A new spectrophotometric method for quantification of potassium solubilized by
      bacterial cultures.
AB  - A new spectrophotometric method was developed for the quantification of potassium
      in the culture broth supernatant of K-solubilizing bacteria. The standard curve
      of potassium with the new method, which is based on the measurement of cobalt,
      showed a regression coefficient (R2) of 0.998. The quantification values of
      potassium obtained with flame photometric method and the newly developed method
      showed a significant correlation (r) of 0.978. The new method depends on the
      precipitation of sodium cobaltinitrite with solubilized potassium in liquid
      medium as potassium sodium cobaltinitrite, which develops bluish green colour by
      the addition of conc. HCl. The intensity of developed colour can be recorded at
      623 nm. This method involves less number of steps, is easy and time saving, and
      can be used for the reliable estimation of available potassium in culture broth
      supernatant of K-solubilizing bacteria.

PMID- 24669670
TI  - Effect of Dactylogyrus catlaius (Jain 1961) infection in Labeo rohita (Hamilton
      1822): innate immune responses and expression profile of some immune related
      genes.
AB  - The monogenean ectoparasite, Dactylogyrus sp. is a major pathogen in freshwater
      aquaculture. The immune responses in parasitized fish were analyzed by
      quantitation of innate immune factors (natural agglutinin level, haemolysin
      titre, antiprotease, lysozyme and myeloperoxidase activities) in serum and immune
      relevant gene expression in gill and anterior kidney. The antiprotease activity
      and natural agglutinin level were found to be significantly higher and lysozyme
      activity was significantly lower in parasitized fish. Most of the genes viz.,
      beta2-microglobulin (beta2M), major histocompatibility complex I (MHCI), MHCII,
      tumor necrosis factor alpha (TNFalpha) and toll-like receptor 22 (TLR22) in gill
      samples were significantly down-regulated in the experimental group. In the
      anterior kidney, the expression of superoxide dismutase and interleukin 1beta
      (IL1beta) were significantly up-regulated whereas a significant down regulation
      of MHCII and TNFalpha was also observed. The down-regulation of most of the genes
      viz, MHCI, beta2M, MHCII, TLR22 and TNFalpha in infected gills indicated a well
      evolved mechanism in this parasite to escape the host immune response. The
      modulation of innate and adaptive immunity by this parasite can be further
      explored to understand host susceptibility.

PMID- 24669671
TI  - Colour preference and light sensitivity in trilobite larvae of mangrove horseshoe
      crab, Carcinoscopius rotundicauda (Latreille, 1802).
AB  - The trilobite larvae of C. rotundicauda were tested to determine their colour
      preference and light sensitivity until their first moulting (25 days post
      hatching) under laboratory conditions. Maximum congregation size of the trilobite
      larvae was found in the white zone respectively where (n = 12) followed by yellow
      (n = 8) and orange (n = 8), which showed the larval preference for lighter zones.
      Morisita's index calculation showed a clumped/aggregated distribution (yellow,
      blue, orange and white) and uniform/hyper dispersed distribution (green, red and
      black) for various colours tested. Trilobite larvae showed least preference for
      brighter regions while tested in the experiment [black; (n = 4) and red; (n =
      5)]. Experiments done to determine the light sensitivity of trilobite larvae
      showed that the larvae had more preference towards ultraviolet lights. The
      maximum congregation size of 38.8 and 40.7% of the larvae was encountered under
      ultraviolet light, when the light sources were kept horizontal and vertical,
      respectively. Overall, results suggested that the trilobite larvae of C.
      rotundicauda, preferred light source of shorter wavelengths (UV light) and
      colours of lighter zone (white, yellow, orange), which might be due to their
      adaptation to their natural habitat for predator avoidance, prey selection and
      water quality.

PMID- 24669672
TI  - Is polio becoming a global challenge?

PMID- 24669673
TI  - Trend of HIV prevalence among pregnant women attending Antenatal Care Unit of
      Bishoftu Hospital, Ethiopia.
AB  - BACKGROUND: HIV prevalence data from prevention of mother-to-child-transmission
      (PMTCT) programs are being utilized to monitor the trend of HIV epidemics that
      helps policy makers to take appropriate action. OBJECTIVE: To determine the trend
      of HIV among pregnant women attending the antenatal care unit of Bishoftu
      Hospital from January 2006 to June 2010. METHODS: A cross-sectional study was
      conducted to determine the prevalence of HIV among pregnant women attending the
      ANC unit of Bishoftu Hospital. Data were analyzed for descriptive statistics and
      Chi-square for trends using SPSS Version 15.0. P-values < or = 0.05 were
      considered significant. RESULTS: A total of 7887 pregnant women were registered
      in the ANC unit of Bishoftu Hospital from January 2006 to June 2010. The overall
      HIV prevalence rate was 5.4%. High prevalence rates were observed in those aged
      between 25-45 years. There was a decline in HIV prevalence from 8.3% in 2006 to
      4.3% in 2010. A total of 1247 pregnant women were tested together with their
      partner. Of these, in 3.1% of the cases, both partners tested positive and 4.9%
      were discordant couples where 2.4% were female positive and male negative while
      2.5% were male positive and female negative. CONCLUSIONS: A remarkable decline in
      HIV prevalence was observed during the five years period The study also revealed
      that relatively higher proportions of HIV infected persons are living in a
      serodiscordant partnership. The involvement of male partners in HIV counseling
      and testing and preventive interventions targeted at HIV-negative individuals
      with discordant partnerships are urgently needed.

PMID- 24669674
TI  - Costs of osteoporosis related fractures in hospital admitted patients, Tigrai,
      Northern Ethiopia: a retrospective study.
AB  - BACKGROUND: Osteoporotic fractures are among the non-communicable diseases
      imposing a growing morbidity and economic burden upon developing countries which
      have limited resources. Despite several studies from other countries, in Ethiopia
      sufficient information regarding the cost of illness related to osteoporotic
      fractures is not available. OBJECTIVE: The aim of the study was to estimate the
      direct and indirect costs attributable to osteoporotic fractures from a patient
      perspective. METHODS: A retrospective review of 1,169 medical records of cases of
      osteoporosis related fracture that had been diagnosed and treated over a two year
      period were selected systematically and included in the analysis. Cost of illness
      was estimated after developing a checklist to extract the direct patient side
      medical costs from individual based data and indirect costs were estimated using
      a human capital approach. RESULT: Analysis of the patient side direct medical
      costs of osteoporotic fracture according to the site of the fracture resulted in
      hip fractures identified as the most expensive fractures accounting for about 25%
      of the total (Median cost, was ETB 237.50 (US$14.09), and Mean = ETB 367.80 (US$
      21.83 per individual patient), while wrist fractures were the least expensive
      accounting for 6.2% (Median ETB 59.00 (US$3.50) and Mean ETB 59.40 (US$ 3.53 per
      individual patient). The average length of hospitalization was 22 days. The
      maximum number of days of hospitalization took place in cases with proximal
      femoral fracture and fractures of the hip and vertebrae, with a median of 25
      days. For every single day increment in inpatient hospital stay there was an
      equivalent increment of ETB 23.27 (US$1.38). The hospital bed occupancy rate for
      the two years due to osteoporotic fractures was 6.8%. The total direct medical
      and indirect cost attributable to osteoporotic fractures during the two year
      period was ETB 1,314,979.00 (US$78,045.08). Of this total, direct medical cost
      and indirect costs incurred by the patients accounted for 49.2% and 50.9%,
      respectively. CONCLUSION: The total patient side cost attributable to
      osteoporotic fractures incurred over a two year time period was over ETB 1.3
      million ($US 78,000). Over 50% of the cost was related to absenteeism from work
      due to hospitalization. From the patients' perspective the costs pose substantial
      burden on patients and their families. Hence, interventions to prevent
      osteoporosis should be implemented.

PMID- 24669675
TI  - Association between khat chewing and intestinal parasitic infestations: a
      community based, cross-sectional study done in Jimma Town, Southwest Ethiopia.
AB  - BACKGROUND: Khat (Catha edulis Forsk), is the psychostimulant herb cultivated in
      East Africa. Khat chewing could have health damaging effect. OBJECTIVE: The aim
      of the present study was to determine the association between khat chewing and
      intestinal parasitic infestation. METHODS: A cross sectional study was conducted
      in Jimma Town in July 2010. Structured questionnaire was administered to 991
      individuals selected by a systematic sampling method. Stool samples were
      collected for the diagnosis of intestinal parasitic infestation. Data analysis
      was done using SPSS Version 16.0 for Windows. RESULTS: Among 991 respondents, 638
      (64.4%) were females, 502 (50.7%) were Oromos, 486 (49%) were Orthodox and 475
      (47.9%) of them were in the age group of 18-24 years old. The current prevalence
      of khat chewing was found to be 52.7%. The prevalence of single to multiple
      parasitic infestations was 33.4%. Negative association (p = 0.000) was recorded
      between the habit of khat chewing and intestinal parasitosis. Non-chewers were
      more affected than chewers. CONCLUSION: Higher proportion of non chewers was
      infested with parasites than chewers, suggesting that khat chewing might have a
      protective role against parasitic infestation. Further investigation on the
      effect of khat extract in in vitro and in vivo is recommended to disclose detail
      mechanisms.

PMID- 24669676
TI  - Bladder exstrophy management at Tikur Anbesa University Hospital, Addis Ababa,
      Ethiopia.
AB  - BACKGROUND: Bladder exstrophy is a rare congenital malformation which presents a
      defect of anterior lower mid abdominal wall, with anteriorly deficient bladder
      wall, widening of symphysis pubis, and epispadias. Management includes single or
      multiple stage repairs and urinary diversion procedures aimed at preservation of
      renal function, maintenance of continence to urine, normal appearing external
      genitalia and satisfactory sexual function. OBJECTIVE: To review the experience
      of Bladder extrophy management at Tikur Anbessa University Hospital, Addis Ababa,
      Ethiopia, in five years. METHODS: Retrospective review of medical records of
      pediatric patients managed for bladder extrophy at Tikur Anbesa Hospital, Addis
      Ababa, Ethiopia from September 1st 2007 to August 31st 2012. RESULTS: A total of
      forty six cases of classic bladder extrophy were seen and managed between
      September 1st, 2007 to August 31st, 2012. Thirty one (67.69%) of them were
      managed by staged repair and 15 (32.61%) were managed by diversion of urine to
      ureterosigmoidostomy pouch (Mainz II pouch). The results of staged repair on 31
      cases (67.39%) were early to assess because most of them were waiting for second
      stage repair. Regarding those managed by Mainz II pouch ureterosigmoidostomy
      14/15 (93.3%) achieved continence to urine which was satisfactory in terms of
      quality of life. CONCLUSION: Ureterosigmoidostomy pouch is a good alternative for
      selected neglected cases in improving the quality of life in the developing
      world.

PMID- 24669677
TI  - Administrative needs of academic partnerships at one Ethiopian university: a
      pilot study.
AB  - BACKGROUND: International university partnerships are important contributors to
      international collaboration, research, and capacity strengthening worldwide. In
      Ethiopia, such partnerships have been initiated at many universities for many
      years. Partnership effectiveness is known to be dependent in part on effective
      administrative practices and infrastructure. OBJECTIVES: This study examines the
      administrative services and resources considered most valuable for sustainable
      partnerships at one Ethiopian university. METHODS: A survey questionnaire was
      distributed to 67 Ethiopian and international colleagues currently or recently
      involved in partnerships at the University of Gondar, of which 10 were completed
      and returned by personnel at the University of Gondar and 8 were returned from
      international colleagues. RESULTS: Both Ethiopian and international respondents
      agreed on the value of partnerships, the dominant challenges, and administrative
      solutions. However, the study also revealed striking differences in perceptions
      of equity and benefit. CONCLUSION: While the study is small, it raises some
      important questions for further study.

PMID- 24669678
TI  - A case report of celiac disease; a report done at Tikur Anbessa Specialized
      Hospital, Addis Ababa.
AB  - A 23 year old male patient who was diagnosed to have malabsorption syndrome
      secondary to celiac disease after he presented with 08 months' duration of
      chronic diarrhea, significant weight loss and marked body weakness with easy
      fatigability. Celiac disease is one of the rare causes of malabsorption in
      African countries. The diagnosis requires appropriate clinical history, high
      index of suspicion, exclusion of common causes of chronic diarrhea and
      confirmation by histology after the characteristic endoscopy appearance is
      identified. Supportive care and gluten restriction was advised and the patient
      has shown marked improvement in symptoms and general wellbeing. Celiac disease
      needs to be considered in patients who present with chronic diarrhea that doesn't
      respond to conventional management.

PMID- 24669679
TI  - Chronic lymphocytic leukemia-associated paraneoplastic pemphigus (bullous
      pemphigoid-like).
AB  - A 50 year old man presented to medical ward of Gondar University hospital with
      painful vesiculobullous skin eruption. Further evaluation revealed underlying
      lymphoproliferative malignancy (chronic lymphocytic leukemia). The synchronous
      presence of these two diseases suggested the skin lesion as a paraneoplastic
      manifestation of the underlying neoplasia.

PMID- 24669680
TI  - Congenital absence of left pulmonary artery in association with isolated
      pulmonary valvular stenosis:.
AB  - Congenital absence of either of the pulmonary arteries is a rare condition but an
      entity known for almost one and half century. Unilateral absence of a pulmonary
      artery commonly occurs in association with other congenital cardiac lesions, but
      can also occur alone. Differential vascularity on plain chest radiograph is the
      usual clue to the diagnosis. Here, a 14 month old patient with congenital absence
      of the left pulmonary artery in association with isolated pulmonary valve
      stenosis is described.

PMID- 24669681
TI  - [Assessment of a portable monitoring device Watch PAT 200 in the diagnosis of
      obstructive sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To assess the accuracy of a wrist worn Watch PAT 200 in diagnosing
      obstructive sleep apnea hypopnea syndrome (OSAHS) by comparing with the standard
      polysomnography (PSG). METHOD: Twenty-eight adults with suspected OSAHS underwent
      a standard in-lab PSG while wearing a Watch PAT 200. PSG events were manually
      scored according to standard criteria (AASM). Watch PAT data were collected
      including changes of apnea hypopnea, sleep stages, peripheral arterial volume,
      signal oxygen saturation and heart rate, and then apnea hypopnea index (AHI) was
      analyzed by an automatic algorithm. RESULT: For PSG, the mean score of AHI was
      (23.00 +/- 21.55)/h, and for Watch PAT, a mean score of AHI was (25.99 +/-
      19.09)/h. There is a statistically positive correlation between PSG-AHI and PAT
      AHI (r = 0.92, P < 0.01). The Coincidence rate of the sleep-wake assessment based
      on 30-second bins between the PSG and Watch PAT 200 was (89 +/- 6)%. CONCLUSION:
      Watch PAT 200 could detected OSAHS based on AHI with comparable accuracy with
      standard PSG. And it would provide a reasonably accurate estimation of sleep and
      wakefulness stages in patients with OSAHS.

PMID- 24669682
TI  - [Surgical management of cervical esophageal carcinoma in 16 cases].
AB  - OBJECTIVE: To investigate the method of surgical management for cervical
      esophageal carcinoma and the feasibility of the operation with preservation of
      laryngeal function. METHOD: Sixteen patients with cervical esophageal carcinoma
      who received surgical treatment were reviewed in our retrospective study. Removal
      of total hypopharynx and larynx and the inversion stripping esophagectomy were
      conducted in thirteen patients, of which one underwent the reconstraction with
      residual larynx and tracheal flap and the other twelve patients underwent the
      reconstraction with gastric-pharyngeal anastomosis. One patient received the
      cervical esophagectomy and partial hypopharyngectomy with laryngotracheal flap.
      The inversion stripping esophagectomy with laryngeal function preservation were
      conducted in two patients, who received the reconstraction with gastric
      pharyngeal anastomosis and preserved total larynx. All the patients were carried
      out the bilateral neck dissections. RESULT: The surgical resection rate was 100%
      and no operative death occurred. The postoperative complications included
      pulmonary infection in two cases, anastomotic fistula in two cases, anastomotic
      stenosis in two cases and congestive heart failure in one case. The retained rate
      of the laryngeal function is 12.5%. The 3-year survival rate is 30.7%, and the 5
      year survival rate is 23.1%. CONCLUSION: The surgical treatment of cervical
      esophageal carcinoma is possible. The inversion stripping esophagectomy without
      thoracotomy is performed to resect the tumor. The esophageal defect could be
      reconstructed by laryngotracheal flap or gastric-pharyngeal anastomosis. The
      laryngeal function should be remained as far as possible according to the
      location and extension of the tumor.

PMID- 24669683
TI  - [Expression and methylation status of IGFBP-rP1 gene in laryngocarcinoma].
AB  - OBJECTIVE: To investigate the relationship between the promoter methylation and
      protein expression of insulin-like growth factor binding protein-related protein
      1(IGFBP-rP1) in laryngeal squamous cell carcinoma (LSCC). METHOD: Methylation
      specific PCR (MSP) approach and immunohistochemistry methods were used to examine
      the methylation status and protein expression of IGFBP-rP1 in 45 samples of
      laryngeal carcinoma and 18 samples of tissues beside cancer. RESULT: For the
      promoter site, methylation frequency of IGFBP-rP1 in tumor specimens (33.3%,
      15/45) was significantly higher than that in corresponding normal tissues (5.6%,
      1/18) (P < 0.05). The protein expression of IGFBP-rP1 in tumor tissues was
      significantly higher than that in corresponding normal tissues (P < 0.05) and was
      inversely correlated with its methylation status of promoter. CONCLUSION:
      Epigenetic silencing of IGFBP-rP1 gene expression by promoter hypermethylation
      may play an important role in LSCC.

PMID- 24669684
TI  - [The role and clinical significance of 12-LOX passway in arachidonic acid
      metabolism induced by phospholipase Cgamma-2 in laryngeal squamous cell
      carcinoma].
AB  - OBJECTIVE: To explore the expression of phospholipase Cgamma-2 (PLCgamma-2),
      lipoxygenase-12 (12-LOX) and arachidonic acid (AA) in laryngeal squamous cell
      carcinoma and to study the the relationship between lipid metabolism and
      laryngeal squamous cell carcinoma. METHOD: In 30 cases of carcinoma tissue and
      peritumoral laryngeal mucosa tissues (confirmed to be normal laryngeal tissues by
      pathology), immunohistochemical method (Streptavidin-peroxidase method, SP
      method) was used for the detection of expression of PLCgamma-2 and 12-LOX, and
      gas chromatography/mass spectrometry (GC/MS) for the content of the arachidonic
      acid in carcinoma tissue and peritumoral normal laryngeal mucosa tissues. RESULT:
      The positive rates of PLCgamma-2 and 12-LOX in carcinoma tissue were higher than
      in peritumoral normal laryngeal mucosa tissues with statistically significance
      differences (P < 0.05). The content of arachidonic acid was lower in carcinoma
      tissue than in peritumoral normal laryngeal mucosa tissues with statistically
      significance difference (P < 0.05). The positive expressions of PLCgamma-2 and 12
      LOX were closely correlated to tnm stage, histological differentiation and lymph
      node metastasis (P < 0.05). The content of arachidonic acid had no significant
      correlations with tnm stage, histological differentiation and lymph node
      metastasis (P > 0.05). Both the expression of PLCgamma-2 and 12-LOX and the
      content of arachidonic acid had no statistically significant correlation with age
      (P > 0.05). CONCLUSION: PLCgamma-2, AA and 12-LOX play important roles in
      laryngeal squamous cell carcinoma. It may be meaningful to the treatment of
      laryngeal carcinoma by suppressing this passway.

PMID- 24669685
TI  - [Clinical observation of intra-operative PTH assay in hyperparathyroidism due to
      parathyroid tumors].
AB  - OBJECTIVE: To investigate the clinical manifestations and diagnostic method of
      hyperparathyroidism due to parathyroid tumors and to evaluate the intra-operative
      detection of parathyroid hormone in surgical treatment. METHOD: Thirty-seven
      cases with functional parathyroid tumors from January 2003 to October 2012 were
      retrospectively analyzed. The clinical manifestation, examination and operation
      method, changes of parathyroid hormone before and after operation were collected.
      RESULT: All cases were definitely diagnosed before operation. The sensitivity and
      the positively predictive values of neck ultrasonography were 86.5% and 97.6%
      respectively, and the same data of Tc-99m-MIBI was 97.2% and 100.0%. The PTH
      levels declined by 84.9% ten minutes after tumor resecting compared with the
      level before operation. The serum calcium and PTH returned to normal levels and
      symptomatic relief occurred after operation. CONCLUSION: Recurrent bone disease,
      long-term urinary calculus and obscure gastrointestinal symptoms were common
      symptoms of hyperparathyroidism due to parathyroid tumors. The neck
      ultrasonography and Tc-99m-MIBI were suitable for location of parathyroid tumors.
      Surgical operation was an effective treatment for parathyroid tumor. Intra
      operative PTH assay would be able to ensure the radical excision and the
      operative safety for functional parathyroid tumors.

PMID- 24669686
TI  - [Application of Doppler combined with flap island on monitoring the post
      operative blood supply of buried free flap].
AB  - OBJECTIVE: To explore the feasible monitoring techniques for the buried free
      flap. METHOD: Buried free flaps in reconstruction were monitored using combined
      monitoring techniques in five cases of advanced hypopharyngeal cancer The
      monitoring effects were analyzed retrospectively. RESULT: The operations were
      carried out successfully and all the five patients got primary healing of
      incision without vascular crisis. Four patients need combined monitoring
      techniques to confirm the microcirculatory results of the buried free flap.
      CONCLUSION: Application of Doppler combined with flap island was feasible on
      monitoring the blood supply of post-operative buried free flap, it is a good
      monitoring technique.

PMID- 24669687
TI  - [The treatment and clinical therapeutic effect analysis in 59 cases of advanced
      supraglottic laryngeal squamous cell carcinoma].
AB  - OBJECTIVE: To compare the therapeutic effect of postoperative radiotherapy with
      surgery alone in advanced supraglottic laryngeal squamous cell carcinoma (LSCC).
      METHOD: According to the treatment methods, 59 patients with advanced
      supraglottic LSCC were divided into surgery plus radiotherapy group (S+R group)
      (33 cases) and surgical group (S group) (26 cases). In S+R group, total
      laryngectomy was performed on 27 patients and partial laryngectomy on 6 patients,
      27 of whom underwent lateral neck dissections; while in S group, total
      laryngectomy was performed on 23 patients and partial laryngectomy on 3 patients,
      24 of whom underwent lateral neck dissections. RESULT: The 3-year overall
      survival rate of S+R and S group were 62.6% and 62.6% respectively, and the 5
      year overall survival rate of S+R and S group were 43.8% and 40.5% respectively.
      But there was no statistically significant difference of survival rate between
      two groups by Log-rank test (P > 0.05). In S+R group, recurrence happened in 5
      cases and the recurrent rate was 15.1%; in S group, recurrence happened in 10
      patients and the recurrent rate was 38.5%, statistically significant difference
      was found between the two recurrent rates (P < 0.05). CONCLUSION: Surgery
      combined with postoperative radiotherapy could not improve the 3-year-or 5-year
      overall survival rate, but could significantly reduced tumor recurrence rate.

PMID- 24669688
TI  - [Expression and significance of TGF-beta1 and BMP-2 in mandibular callus].
AB  - OBJECTIVE: To investigate the expressions of transforming growth factor beta1
      (TGF-beta1) and bone morphogenetic protein-2 (BMP-2) in human mandible fracture
      callus and their quantity changes in the process of healing. METHOD: Thirty
      callus samples from the fractured mandible bone stumps were collected during
      operation, and two callus samples were collected from the angle-square jaw
      patients as controls. The expressions of TGF-beta1 and BMP-2 were test by the
      immunohistochemistry technic-SABC-staining in different periods of human
      fractured mandibular callus and in osseous tissue of normal angle of mandible.
      RESULT: The TGF-beta1 and BMP-2 were expressed in callus of different periods but
      not in normal bone tissue. The expression of TGF-beta1 increased slowly during
      the first three weeks after fracture and reached its maximum in the third week,
      and then weakened gradually. The expression of BMP-2 increased gradually during
      the first two weeks after fracture and reached its maximum in the second week,
      then the expression weakened gradually. CONCLUSION: (1) BMP-2 may be one of the
      factors promoting the repair of fracture. (2) TGF-beta1 could be another signal
      pathway in repairment of fracture. (3) There could exist some synergistic effects
      between TGF-beta1 and BMP-2 in the process of fracture healing.

PMID- 24669689
TI  - [Clinical analysis of 337 cases of chronic rhinosinusitis].
AB  - OBJECTIVE: To explore the clinical symptoms and signs situation of chronic
      rhinosinusitis, for future treatment provides the basis. METHOD: The clinical
      data of 337 patients with chronic sinusitis were analyzed, using SPSS 18.0
      software and conducted Person chi-square test and Kruskal-Wallis test to
      analysis. RESULTS: VAS total score of chronic nasal sinusitis patients is 15.9 +/
      5.7. The three top of severe symptoms were: stuffy nose 56 cases (16.6%), nasal
      secretions or postnasal drip 23 cases (6.8%) and dizziness or headache 11 cases
      (3.3%), there are statistically significant differences (chi2 = 430.923, P <
      0.01). Lund-Kennedy score found side with mucosa edema and secretion serious
      degree higher than nasal polyp, there are statistically significant difference
      (chi2 = 128.684, P < 0.01). Lund-Mackay score showed that the three top parts of
      all shadow were: maxillary sinus 314 side (46.6%), OMC 135 side (20.0%) and the
      former screen 112 side (16.6%), there are statistically significant differences
      between groups (chi2 = 803.274, P < 0.01). The pearson correlation coefficient r
      between VAS score and Lund-Kennedy score is 0.516, there are correlation (P <
      0.05). VAS score and Lund-Mackay (r = 0.213), there are not correlation (P >
      0.05). CONCLUSION: Comprehensive treatment should be proceeded according to
      different symptom severity and sinus lesions parts with patients, grasped the
      surgery procedures strictly, so as to improve the cure rate.

PMID- 24669690
TI  - [Synergistic lethal effects of cetuximab combined with chemotherapy and/or
      radiotherapy in laryngeal squamous carcinoma cells].
AB  - OBJECTIVE: To determine the sensitivity of cetuximab induced apoptosis in
      laryngeal squamous carcinoma cells Hep-2, and to evaluate the synergistic killing
      effects and regulation mechanism of cetuximab alone or cetuximab in combination
      with chemotherapeutic agents (cisplatin) or radiation means on Hep-2 cells.
      METHOD: To investigate the cytotoxicities of cetuximab, cisplatin and radiation,
      cell counting kit-8 (CCK-8) assay was used for the detection of cell growth
      inhibition ratio, and fluorescence activated cell sorter FACS for the apoptotic
      rate and cell cycle distribution. RESULT: Cetuximab had inhibitive effect on Hep
      2 cells within a certain range of concentration in a time- and dose-dependence
      manner. The inhibition concentration 50% (IC50) of cetuximab on Hep-2 cells for
      24 h was 1 036.84 microg/ml. For application of cisplatin and radiation, the
      apoptotic rate of Hep-2 cell was higher by combining with cetuximab than their
      single or combined administration. Moreover, the cell cycle arrested at G0/G1
      phase. CONCLUSION: Laryngeal cancer Hep-2 cells was sensitive to the cetuximab
      induced apoptosis. Cetuximab combined with cisplatin and/or radiation can
      increase the antiproliferative effects on Hep-2 cells. These findings suggest the
      synergistic combination of cetuximab and cytotoxic agents was sequence depended.

PMID- 24669691
TI  - [Vestibular-evoked myogenic potential in response to bone-conducted sound in
      patients with otosclerosis].

PMID- 24669692
TI  - [The cervical dermatoglyphic character of 229 Chinese patients and its
      application in incision design for the cervical lymph nodes dissection].
AB  - OBJECTIVE: To summarize the cervical dermatoglyphics distribution in 229
      participants, and to design dermatoglyphic incision for cervical lymph nodes
      dissection, including II , III, IV or/and V regions, in accordance with the
      requirement for cosmetology. METHOD: To keep the patient's head right forward
      when the number and locations of the dermatoglyphy were collected by macroscopic
      observation. Upper Cricoid-Region is defined as the region above the cricoids,
      and Cricoids-Collarbone-Region is referred to the region below the cricoids. The
      relationship among the distribution of cervical dermatoglyph, patients' age,
      gender, and body mass index were analyzed. According to the distribution of
      cervical dermatoglyph, when performing the regional cervical lymph nodes
      dissection in patients with laryngocarcinoma and thyroid cancer, cervical
      dermatoglyphy incision or parallel dermatoglyphy incision were designed, and the
      operation time, operative complications, and cosmetology effects after surgery
      were observed. RESULT: Distribution of cervical dermatoglyphics was statistically
      correlated to the age, gender, and body mass index (P < 0.05) of patients. The
      follow-up time were 12 months to 49 months, 19 months on average. Average
      operating time of unilateral lymph nodes dissection was (46 +/- 12) minutes.
      Patients undergone the designs of cervical dermatoglyphy incision or parallel
      dermatoglyphy incision, suffered neither skinflap necrosis nor accessory nerve
      injury. One patient had lymphatic fistula after surgery, and relieved by
      conservative treatment. One with T3 N2 M0 laryngocarcinoma got V region lymph
      nodes recurrence 6-months after surgery. CONCLUSION: The cervical lymph nodes
      dissection with dermatoglyphy design is safe with prominent cosmetology effects.
      It will take a little longer time to perform the neck dissection with the
      dermatoglyphy incision in the beginning.

PMID- 24669693
TI  - [Clinical analysis of foreign body ingestion of button cell in children].
AB  - OBJECTIVE: To improve diagnosis and treatment level of foreign body ingestion of
      button cell in children. METHOD: Among the 14 cases with foreign bodies ingestion
      of button cell, 6 cases in esophageal, 7 cases in stomach and lower
      gastrointestinal tract, 1 case with multiple foreign bodies both in esophagus and
      stomach. Seven cases in stomach and lower gastrointestinal tract were closely
      observed without special treatment, 6 cases in esophageal, underwent
      esophagoscopy and removal of foreign body under general anesthesia, 1 case with
      multiple foreign bodies in esophagus and stomach underwent esophagoscopy and
      electronic gastroscopy and then removal of foreign body. All patients had
      symptomatic treatments after removal of foreign body. The average age is 2 years
      and 1 month. RESULT: After the removal of button cell, Foreign bodies in stomach
      and lower gastrointestinal tract in 7 cases were all discharged spontaneously.
      For the 6 cases in esophagus, 4 cases were cured, 1 case had esophageal
      stricture, 1 cased died. 1 case with multiple foreign bodies in both esophagus
      and stomach was cured. CONCLUSION: Esophageal foreign body has strong
      corrosiveness and would cause serious damages even to threaten children's life.
      It also may lead to esophageal stricture. The key point to cure this disease is
      to diagnose timely and to operate as soon as possible. Because neutralize of
      digestive juices and low probability of incarceration, with close observation,
      the foreign bodies of stomach and lower gastrointestinal tract can discharge
      spontaneously.

PMID- 24669694
TI  - [Nocturnal groaning-catathrenia (a report of one case)].

PMID- 24669695
TI  - [A case report of primary tuberculosis of thyroid and misdiagnosis analysis].

PMID- 24669696
TI  - [The neck multiple space infection: clinical analysis of 6 cases].

PMID- 24669697
TI  - [Treatment of traumatic perforation of tympanic membrane with lens paper under
      ear endoscope].

PMID- 24669698
TI  - [A case of epiglottic pleomorphic adenoma].
AB  - The pleomorphic adenoma of epiglottis is rare. When the tumor grows larger, some
      patients may have symptoms of pharyngeal foreign body sensation, but other
      patients have no obvious symptom. The tumor is mainly found through indirect
      laryngoscopy or electronic laryngoscopy. This disease can be confirmed by
      pathological diagnosis after tumor resection.

PMID- 24669699
TI  - [A case report of giant cell tumor of larynx].
AB  - Giant cell tumor (GCT) is rare and it mainly occurred in male patients. A man of
      65 years-old with progressive dyspnea has a 4 cm x 4 cm x 3 cm tumor mass under
      the right vocal fold originated from right-thyroid cartilage and the
      parapharyngeal space. The right false vocal was involved in the computed
      tomography (CT) imaging and laryngoscope. Microscopically, the tumors had an
      expansile, infiltrative growth and consisted of numerous multinucleated
      osteoclast-like giant cells within a cellular stroma composed of plump and oval
      mononuclear cells. The patient underwent partial laryngectomy and has been
      followed up for 6 months without recurrence or metastasis.

PMID- 24669700
TI  - [Two cases of primary malignant lymphoma of thyroid].
AB  - Two 78-years old-old man and woman presented with thyroid tumor without a past
      history of chronic thyroiditis. Physical examinations showed touchable lumps in
      thyroid without other lymph nodes swelling or extra nodal lesions. Two cases both
      had thyroid function test, color Doppler ultrasound examination, computed
      tomography (CT) scan and fine needle aspiration (FNA) before surgery. The
      patients underwent partial thyroidectomy or subtotal thyroidectomy. Postoperative
      pathologic findings were consistent with malignant lymphoma. The diagnosis mainly
      relied on the postoperative pathologic findings.

PMID- 24669701
TI  - [Recent advances in DNA vaccines against allergic airway disease: a review].
AB  - DNA vaccine is used in infectious diseases initially, and later is applied in
      neoplastic diseases, allergic diseases and other fields with the further
      understanding of DNA vaccine and the development of genetic engineering. DNA
      vaccine transfers the genes encoding exogenous antigens to plasmid vector and
      then is introduced into organism. It controls the antigen proteins synthesis,
      thus induces specific humoral and cellular immune responses. So it has a broad
      application prospect in allergic diseases. Compared with the traditional protein
      vaccines used in specific immunotherapy, DNA vaccine has many advantages,
      including high purity and specificity, and improvement of patients' compliance
      etc. However, there are still two unsolved problems. First, the transfection rate
      of unmodified naked DNA plasmid is not high, Second, it's difficult to induce
      ideal immune response. In this study, we will review the progress of DNA vaccine
      applications in respiratory allergic diseases and its various optimization
      strategies.

PMID- 24669702
TI  - [Simultaneous dual protein labeling].

PMID- 24669703
TI  - [Inductively coupled plasma mass spectrometry based bioanalysis].

PMID- 24669704
TI  - [Recent advances in preparation of novel chromatographic stationary phases with
      carbon nanotubes].
AB  - Carbon nanotubes (CNTs) as a new functional material have attracted the interest
      of scientists and engineers in analytical chemistry, due to their excellent
      physical, chemical and mechanical properties. The preparation of chromatographic
      stationary phases with CNTs has been performed by packing method or in situ
      catalytic chemical vapor deposition. The deposition of CNTs on a chromatographic
      solid matrix (e. g. silica micro-particles or organic polymer microspheres) was
      carried out to generate a packing material for high performance liquid
      chromatography. Capillary monolithic columns for liquid chromatography were also
      prepared by embedding CNTs in polymer monolithic columns. Columns with CNTs have
      the unique advantages in the separation of aromatic compounds for the tr electron
      system of CNTs. Herein, the recent applications of CNTs in the preparation of
      chromatographic stationary phases are reviewed, including gas chromatography and
      liquid chromatography. The future developments in this field are also prospected.

PMID- 24669705
TI  - [Application of liquid chromatography-mass spectrometry in the research of
      Alzheimer's disease].
AB  - Liquid chromatography-mass spectrometry (LC-MS) combining with both highly
      efficient separation and detection is widely applied to chemistry, medicine,
      pharmacy biochemistry etc. Particularly, the application of LC-MS to clinic
      chemistry opened a new chapter for diagnosis technologies. Alzheimer' s disease
      (AD), also called as senile dementia, is the fourth leading cause of death in
      modern society. With the rapid aging of population, the prevention and treatment
      of AD need to be strengthened. In this review, we briefly introduce the new LC-MS
      developments and discuss the applications of LC-MS techniques in AD research in
      the last three years.

PMID- 24669706
TI  - [Simultaneous determination of clopidol, sulfonamide and quinolone residues in
      chickens by ultra performance liquid chromatography-tandem mass spectrometry].
AB  - An analytical method for the simultaneous determination of clopidol,
      sulfadiazine, sulfamethazine, sulfametoxydiazine, sulfamethoxypyridazine,
      norfloxacin, ofloxacin, ciprofloxacin, enrofloxacin in chickens by ultra
      performance liquid chromatography coupled with tandem quadrupole mass
      spectrometry (UPLC-MS/MS) in positive ion mode with multiple reaction monitoring
      (MRM) has been developed and validated. The samples were homogenized and
      extracted with acetonitrile. After defatted with high speed frozen
      centrifugation, the supernatant solution was evaporated and the residue was
      dissolved with the mobile phase and defatted with n-hexane. It was then analyzed
      with UPLC-MS/MS. The limit of detection of this method was 0.1 microg/kg, and the
      limit of quantification was 0.5 microg/kg. The average recoveries (spiked at the
      levels of 0.5, 1.0, 2.0 microg/kg) ranged from 81.5% to 97.6%, with the relative
      standard deviations between 2.1% and 8.9%. The results demonstrated that the
      method is simple, accurate and suitable for the identification and quantification
      of these drug residues in chickens.

PMID- 24669707
TI  - [Determination of 51 carbamate pesticide residues in vegetables by liquid
      chromatography-tandem mass spectrometry based on optimization of QuEChERS sample
      preparation method].
AB  - The raw extracts of six vegetables (tomato, green bean, shallot, broccoli, ginger
      and carrot) were analyzed using gas chromatography-mass spectrometry (GC-MS) in
      full scan mode combined with NIST library search to confirm main matrix
      compounds. The effects of cleanup and adsorption mechanisms of primary secondary
      amine (PSA) , octadecylsilane (C18) and PSA + C18 on co-extractives were studied
      by the weight of evaporation residue for extracts before and after cleanup. The
      suitability of the two versions of QuEChERS method for sample preparation was
      evaluated for the extraction of 51 carbamate pesticides in the six vegetables.
      One of the QuEChERS methods was the original un-buffered method published in
      2003, and the other was AOAC Official Method 2007.01 using acetate buffer. As a
      result, the best effects were obtained from using the combination of C18 and PSA
      for extract cleanup in vegetables. The acetate-buffered version was suitable for
      the determination of all pesticides except dioxacarb. Un-buffered QuEChERS method
      gave satisfactory results for determining dioxacarb. Based on these results, the
      suitable QuEChERS sample preparation method and liquid chromatography-positive
      electrospray ionization-tandem mass spectrometry under the optimized conditions
      were applied to determine the 51 carbamate pesticide residues in six vegetables.
      The analytes were quantified by matrix-matched standard solution. The recoveries
      at three levels of 10, 20 and 100 microg/kg spiked in six vegetables ranged from
      58.4% to 126% with the relative standard deviations of 3.3%-26%. The limits of
      quantification (LOQ, S/N > or = 10) were 0.2-10 microg/kg except that the LOQs of
      cartap and thiofanox were 50 microg/kg. The method is highly efficient, sensitive
      and suitable for monitoring the 51 carbamate pesticide residues in vegetables.

PMID- 24669709
TI  - [Determination of twenty free amino acids in flue-cured tobacco leaves using
      ultra performance liquid chromatography-single quadruple mass spectrometry and
      pre-column derivatization].
AB  - Free amino acids in flue-cured tobacco leaves were investigated using the ultra
      performance liquid chromatography-single quadruple mass spectrometry detection
      and pre-column derivatization method. The validation results showed that the
      method could meet the analytical requirements. A total of 138 tobacco leaf
      samples were collected from 14 provinces in China in 2011 in which the free amino
      acids were determined. The relative standard deviations (RSDs) of the contents of
      free amino acids in different growing regions ranged from 28.50%-94.20%, and
      those of asparagine and glutamine were over 80%. The RSDs of the contents of free
      amino acids in full aroma tobacco leaves were larger than those in fresh aroma
      and medium aroma tobacco leaves. The principal component analysis (PCA) and non
      parameter Mann-Whitney U test were used for data analysis. The free amino acids
      of the same aroma type grown in different regions or different aroma types in the
      same province showed great variation. The contents of free amino acids of full
      aroma tobacco grown in Southeast region were much lower than those in Huanghuai
      region. The contents of free amino acids in Hunan province were much lower than
      the average contents. The results showed that free amino acids in flue-cured
      tobacco leaves were affected by the growing region.

PMID- 24669708
TI  - [Simultaneous determination of six estrogens in different water bodies by solid
      phase extraction and ultra performance liquid chromatography coupled with triple
      quadrupole mass spectrometry].
AB  - A method has been developed for the simultaneous determination of six estrogens:
      (estriol, 17-beta-estradiol, 17-alpha-estradiol, estrone, ethinyloestradiol,
      diethylstilbestrol) in water environment by solid phase extraction and ultra
      performance liquid chromatography couple with triple quadrupole mass
      spectrometry. After enriched and purified by an HLB solid phase extraction
      column, the six estrogens were separated by a BEH C18 column and then determined
      by MS/MS with multiple reaction monitoring (MRM) mode. The quantification was
      achieved by internal standard method, with estriol-D3, estradiol-D2 and
      diethylstilbestrol-D8 as the internal standards. Good linear relationships were
      obtained in the mass concentration range of 1.0-100 microg/L with high
      correlation coefficients over 0. 998 2. The limits of detection and
      quantification for the six estrogens were 0.27-0.45 ng/L and 1.08-1.78 ng/L,
      respectively. The recoveries were in the range of 68.3%-97.4% at the three spiked
      levels and with the relative standard deviations below 15%. The method shows high
      sensitivity, good precision, extensive analytical range and high analytical
      speed. It was successfully applied to the simultaneous detection of the six
      estrogens in four different water bodies including surface water, waste water,
      source water of drinking and domestic water.

PMID- 24669710
TI  - [Simultaneous determination of five Amadori compounds in tobacco by high
      performance liquid chromatography-mass spectrometry].
AB  - A method of high performance liquid chromatography-triple quadrupole mass
      spectrometry (HPLC-QqQ MS) in multiple reaction monitoring (MRM) mode for
      simultaneous determination of five Amadori compounds in tobacco has been
      developed. The separation was performed on an XBridge Amide column (250 mm x 4.6
      mm, 3.5 microm) by gradient elution using methanol and water as mobile phases.
      The linearity of this method was good with the correlation coefficients (r) of
      0.9895-0.9989. The limits of detection (S/N = 3) were from 3.51 microg/L to 14.86
      microg/L, and the limits of quantitation (S/N = 10) were from 10.18 microg/L to
      44.58 microg/L. The recoveries varied from 92.6% to 123.6% with the relative
      standard deviations (RSDs) less than 9.4%. The established method is rapid,
      accurate, robust and convenient, and it could be applied to the measurement of
      the five Amadori compounds in tobacco and cigarettes.

PMID- 24669711
TI  - [International comparison APMP.QM-P23: determination of benzoic acid in orange
      juice].
AB  - A method was developed for the separation and determination of benzoic acid in
      orange juice by high performance liquid chromatography-ultraviolet detection
      (HPLC-UV) and liquid chromatography-isotope dilution mass spectrometry (LC-IDMS).
      National Institute of Metrology (NIM) of China participated the international
      comparison activity organized by Asia Pacific Metrology Programme (APMP) and got
      good results using this method. The effects of several important factors, such as
      the chromatographic conditions and sample preparation conditions, were
      investigated to acquire optimum conditions. A method of uncertainty determination
      was also developed which can be used in similar measurements of uncertainty. The
      limit of detection (LOD, S/N > 3) of HPLC-UV method was 0.75 mg/kg, and the
      recovery of benzoic acid in orange juice at the spiked level 100 mg/kg was 99.4%.
      The LOD of LC-IDMS method was 0.05 mg/kg, and the recovery of benzoic acid at the
      same spiked level was 99.6%. The final determination result of benzoic acid in
      the orange juice sample by both methods was (102.0 +/- 2.1) mg/kg (coverage
      factor kappa = 2). The two methods are both simple, accurate, reliable and
      reproducible. The LC-IDMS method is more suitable for the determination of
      benzoic acid at low concentrations due to its high sensitivity.

PMID- 24669712
TI  - [Simultaneous determination of delta13C values of glycerol and ethanol in wine by
      liquid chromatography coupled with isotope ratio mass spectrometry].
AB  - A novel procedure was established for the characterization of delta13C values of
      glycerol and ethanol in wine by liquid chromatography-isotope ratio mass
      spectrometry (LC-IRMS). Several parameters influencing the separation of glycerol
      and ethanol from wine matrix were optimized. The precision and accuracy of the
      proposed method were 0.15 per thousand to 0.26 per thousand and 0.11 per thousand
      to 0.28 per thousand, respectively. The results obtained for 40 wine samples
      displayed that the delta13C value of glycerol ranged from--26.87 per thousand to-
      32.96 per thousand and that of ethanol ranged from--24.06 per thousand to--28.29
      per thousand. Close correlations (R = 0.82) were obtained between the delta13C
      values of glycerol and ethanol. The proposed method didn't need complex sample
      treatment, and the delta13C values of glycerol and ethanol in wine can be
      simultaneously determined, thus improving the method in terms of simplicity and
      speed compared with traditional methods.

PMID- 24669713
TI  - [Effect of alcoholic strength on the determination of ethyl carbamate in Chinese
      spirits by high performance liquid chromatography-fluorescence detection].
AB  - A high performance liquid chromatography-fluorescence detection (HPLC-FLD) method
      was established for rapid determination of ethyl carbamate (EC) in Chinese
      spirits. Through the analysis and comparison of the EC peak areas in different
      alcoholic strengths determined by HPLC-FLD, the effect of alcoholic strength on
      the determination of the content of EC was found. The alcoholic strength and the
      peak area of EC showed good linearity in the range of 5% to 65% (v/v) alcohol
      content, and the correlation coefficients (R2) were higher than 0.98.
      Furthermore, the conversion between the peak area of EC with different alcoholic
      strengths was established by the relative correction coefficient. The method
      showed a good linearity in the range of 10 to 500 microg/L for EC with the
      average recoveries of 98.9%-108.2% and RSDs of 0.6%-4.9%. The reliability of the
      established HPLC-FLD method was evaluated by comparison with GC-MS method. The
      results showed that the results of two methods were not significantly different.
      The developed method is simple, sensitive, accurate, and suitable for the rapid
      determination of EC in Chinese spirits.

PMID- 24669714
TI  - [Determination of 34 pesticide residues in rice, proso millet and wheat with
      QuEChERS-on line gel permeation chromatography-gas chromatography-mass
      spectrometry].
AB  - A method for the simultaneous determination of 34 pesticides in rice, proso
      millet and wheat by QuEChERS coupled with on line gel permeation chromatography
      gas chromatography-mass spectrometry (GPC-GC-MS) was developed. The effects of
      the sample weight, extraction solvent, sorbent for purification were
      investigated. The matrix effect and the usefulness of analyte protectant were
      also studied. The identification and quantification were performed by GPC-GC-MS
      in selected ion monitoring (SIM) mode and exrternal standard method. The
      calibration curves of the 34 pesticides showed good linearity in th range of
      0.0125-0.2 mg/L with thea correlations coefficients (r2) between 0.968 and 0.999.
      The average recoveries were 94.5%-117.1%, 83.1%-121.7% and 93.1%-120.2% with the
      relative standard deviations (RSDs, n = 6) no more than 14.5%, 15.1% and 15.2% in
      rice, proso millet and wheat samples, respectively. The LODs of this method were
      0.0281-5.31, 0.0282-4.82 and 0.0273 -5.13 microg/kg (S/N = 3) for rice, proso
      millet and wheat samples, respectively. The low cost and less consumption of
      reagents of this method are in accordance with the concept of green chemistry.
      The convenient operation and versatility of this method are suitable for the fast
      screening and detection of the 34 pesticide residues in rice, proso millet and
      wheat.

PMID- 24669715
TI  - [Determination of benzene series in marine sediment by headspace solid phase
      microextraction-gas chromatography-mass spectrometry].
AB  - A method was developed for the determination of benzene series (BTEX) in marine
      sediment by headspace solid phase microextraction (HS-SPME) and gas
      chromatography-mass spectrometry (GC-MS). The conditions for extraction and gas
      chromatography, such as the amount of salt added, equilibrium time, extraction
      temperature, extraction time, desorption time and injection temperature, were
      optimized. The analytes were quantitatively analyzed by the internal standard
      method. The results showed that the linear correlation coefficients of BTEX
      compounds were from 0.995 to 0.999 in the range of 0.500-20.0 ng/g. The detection
      limits of this method were from 0.081 8 to 0. 175 ng/g, with the RSDs of inter-
      and intra-day of 1.2%-3.6% (n = 5) and 0.4%-6.3% (n = 3). The average recoveries
      under two different spiked concentrations (2.0 and 15.0 ng) were 61.7%-79.5% and
      77.1%-85.6% with RSDs of 5.4%-9.6% and 3.9%-7.6% (n = 5), respectively. This
      method is quick, sensitive, simple, accurate and reproducible. It can be used to
      analyze the marine sediment samples with trace BTEX.

PMID- 24669716
TI  - [Determination of the total amount of maleic acid and maleic anhydride in starch
      and its products by high performance liquid chromatography-tandem mass
      spectrometry].
AB  - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS)
      method was established for the determination of the total amount of maleic acid
      and maleic anhydride in starch and its products. The samples were extracted with
      50% (v/v) methanol and hydrolyzed by alkaline, then analyzed by HPLC-MS/MS, and
      quantified with the external standard method. The mass spectrometry was operated
      with electrospray in negative ionization mode. The multiple reaction monitoring
      (MRM) mode was employed involving the transition of the precursor ion to two
      selected product ions, in which one pair was for quantification (m/z 115.0 >
      71.1) and the other pair was for identification (m/z 115.0 > 27.1). The results
      indicated that no significant matrix effect was found for the spiked samples. The
      recoveries of maleic acid spiked in starch and its products were 80.2%-115.3% at
      spiked levels of 0.5-1,000 mg/kg. The relative standard deviations (RSDs) were
      less than 12% (n = 6). The limits of detection (LOD) and quantification (LOQ)
      were 0.1 and 0.5 mg/kg for maleic acid and maleic anhydride, respectively. The
      method is rapid, sensitive and reproducible for the determination of the total
      amount of maleic acid and maleic anhydride in starch and its products and shows
      great potential for routine analysis

PMID- 24669717
TI  - [Determination of lutein in infant formula milk powder using ultra-high
      performance liquid chromatography].
AB  - An ultra-high performance liquid chromatography (U-HPLC) method for the
      determination of lutein in the infant formula milk powder was developed. The
      sample was extracted with acetone and defatted using freezing centrifugation
      method. The U-HPLC separation was achieved using a YMC Carotenoid C30 column (150
      mm x 4.6 mm, 3 microm) with the mixture of methanol/methyl tert-butyl ether (70:
      30, v/v) as the mobile phase under isocratic elution. The flow rate was 0.5
      mL/min and the column oven temperature was 25 degrees C. The injection volume was
      5 microL. It was detected on a photodiode array detector at a wavelength of 445
      nm. The results showed that the linear range was 20-500 microg/L (r = 0.9999),
      and the limit of quantification was 20 microg/L. The mean recoveries of lutein
      varied from 97.9% to 104.4% spiked at 50, 250 and 2,000 microg/kg. The
      established method is simple, accurate and sensitive for the rapid determination
      of lutein in infant formula milk powder.

PMID- 24669718
TI  - [Determination of ten photoinitiators in fruit juices and tea beverages by solid
      phase micro-extraction coupled with gas chromatography/mass spectrometry].
AB  - A method for the determination of ten photoinitiators (PIs), benzophenone, ethyl
      4-dimethylaminobenzoate, 1-hydroxycyclohexyl-phenylketone, 4-methylbenzophenone,
      2-ethylhexyl-4-dimethylaminobenzoate, 4-chlorobenzophenone, 2-chlorothioxanthone,
      2-isopropylthio-xanthone, 2,2-dimethoxy-2-phenylacetophenone, methyl 2
      benzoylbenzoate, in 13 kinds of fruit juice and 3 kinds of tea beverage has been
      established, using solid-phase micro-extraction (SPME) combined with
      chromatography/mass spectrometry (GC/MS). At first, the major factors of SPME,
      extraction time and temperature, were studied through orthogonal experiment. Then
      the optimal operation conditions were obtained via the refinement of various
      factors. After the sample was extracted by SPME, it was desorbed for target
      analytes in sampling inlet for 3 min, and separated on an HP-5MS column, then
      detected by MS in selected ion monitoring mode, and quantified through
      calibration curve. The working curves were obtained using sample matrix in order
      to eliminate the matrix interference. The linear range was from 0.3 microg/L to
      60 microg/L and the detection limit range was from 3 ng/L to 16 ng/L. The samples
      were determined five times with four different spiked levels individually and the
      relative standard deviations of all the samples were less than 14.5%. This
      determination method was applied in 16 kinds of packed beverages with different
      brands and different species. Benzophenone had been detected from all the
      samples. 4-Methylbenzophenone, 2-ethylhexyl-4-dimethylaminobenzoate, 2
      isopropylthioxanthone, 1-hydroxycyclohexyl-phenylketone and 2-chlorothioxanthone
      had been detected from a portion of samples. Simultaneous determination was
      achieved for the ten PIs. These results provide a reference to determine the PIs
      migrated from packing materials in beverage. This method is simple, high
      sensitive and non-polluting.

PMID- 24669719
TI  - On modeling animal movements using Brownian motion with measurement error.
AB  - Modeling animal movements with Brownian motion (or more generally by a Gaussian
      process) has a long tradition in ecological studies. The recent Brownian bridge
      movement model (BBMM), which incorporates measurement errors, has been quickly
      adopted by ecologists because of its simplicity and tractability. We discuss some
      nontrivial properties of the discrete-time stochastic process that results from
      observing a Brownian motion with added normal noise at discrete times. In
      particular, we demonstrate that the observed sequence of random variables is not
      Markov. Consequently the expected occupation time between two successively
      observed locations does not depend on just those two observations; the whole path
      must be taken into account. Nonetheless, the exact likelihood function of the
      observed time series remains tractable; it requires only sparse matrix
      computations. The likelihood-based estimation procedure is described in detail
      and compared to the BBMM estimation.

PMID- 24669720
TI  - A protected area influences genotype-specific survival and the structure of a
      Canis hybrid zone.
AB  - It is widely recognized that protected areas can strongly influence ecological
      systems and that hybridization is an important conservation issue. However,
      previous studies have not explicitly considered the influence of protected areas
      on hybridization dynamics. Eastern wolves are a species of special concern and
      their distribution is largely restricted to a protected population in Algonquin
      Provincial Park (APP), Ontario, Canada, where they are the numerically dominant
      canid. We studied intrinsic and extrinsic factors influencing survival and cause
      specific mortality of hybrid and parental canids in the three-species hybrid zone
      between eastern wolves, eastern coyotes, and gray wolves in and adjacent to APP.
      Mortality risk for eastern wolves in areas adjacent to APP was significantly
      higher than for other sympatric Canis types outside of APP, and for eastern
      wolves and other canids within APP. Outside of APP, the annual mortality rate of
      all canids by harvest (24%) was higher than for other causes of death (4-7%).
      Furthermore, eastern wolves (hazard ratio = 3.5) and nonresidents (transients and
      dispersing animals, hazard ratio = 2.7) were more likely to die from harvest
      relative to other Canis types and residents, respectively. Thus, eastern wolves
      dispersing from APP were especially vulnerable to harvest mortality. For
      residents, eastern wolf survival was more negatively influenced by increased road
      density than for other Canis types, further highlighting the sensitivity of
      eastern wolves to human disturbance. A cycle of dispersal from APP followed by
      high rates of mortality and hybridization appears to maintain eastern wolves at
      low density adjacent to APP, limiting the potential for expansion beyond the
      protected area. However, high survival and numerical dominance of eastern wolves
      within APP suggest that protected areas can allow rare hybridizing species to
      persist even if their demographic performance is compromised and barriers to
      hybridization are largely absent in the adjacent matrix.

PMID- 24669721
TI  - The roles of competition and habitat in the dynamics of populations and species
      distributions.
AB  - The role of competition in structuring biotic communities at fine spatial scales
      is well known from detailed process-based studies. Our understanding of
      competition's importance at broader scales is less resolved and mainly based on
      static species distribution maps. Here, we bridge this gap by examining the joint
      occupancy dynamics of an invading species (Barred Owl, Strix varia) and a
      resident species (Northern Spotted Owl, Strix occidentalis caurina) in a 1000-km
      study area over a 22-year period. Past studies of these competitors have focused
      on the dynamics of one species at a time, hindering efforts to parse out the
      roles of habitat and competition and to forecast the future of the resident
      species. In addition, while these studies accounted for the imperfect detection
      of the focal species, no multi-season analysis of these species has accounted for
      the imperfect detection of the secondary species, potentially biasing inference.
      We analyzed survey data using models that combine the general multistate-multi
      season occupancy modeling framework with autologistic modeling, allowing us to
      account for important aspects of our study system. We found that local extinction
      probability increases for each species when the other is present; however, the
      effect of the invader on the resident is greater. Although the species prefer
      different habitats, these habitats are highly correlated at the patch scale, and
      the impacts of invader on the resident are greatest in patches that would
      otherwise be optimal. As a consequence, competition leads to a weaker
      relationship between habitat and Northern Spotted Owl occupancy. Colonization and
      extinction rates of the invader are closely related to neighborhood occupancy,
      and over the first half of the study the availability of colonists limited the
      rate of population growth. Competition is likely to exclude the resident species,
      both through its immediate effects on local extinction and by indirectly lowering
      colonization rates as Northern Spotted Owl occupancy declines. Our analysis
      suggests that dispersal limitation affects both the invasion dynamics and the
      scale at which the effects of competition are observed. We also provide
      predictions regarding the potential costs and benefits of managing Barred Owl
      populations at different target levels.

PMID- 24669722
TI  - What do predators really want? The role of gerbil energetic state in determining
      prey choice by Barn Owls.
AB  - In predator-prey foraging games, predators should respond to variations in prey
      state. The value of energy for the prey changes depending on season. Prey in a
      low energetic state and/or in a reproductive state should invest more in foraging
      and tolerate higher predation risk. This should make the prey more catchable, and
      thereby, more preferable to predators. We ask, can predators respond to prey
      state? How does season and state affect the foraging game from the predator's
      perspective? By letting owls choose between gerbils whose states we
      experimentally manipulated, we could demonstrate predator sensitivity to prey
      state and predator selectivity that otherwise may be obscured by the foraging
      game. During spring, owls invested more time and attacks in the patch with well
      fed gerbils. During summer, owls attacked both patches equally, yet allocated
      more time to the patch with hungry gerbils. Energetic state per se does not seem
      to be the basis of owl choice. The owls strongly responded to these subtle
      differences. In summer, gerbils managed their behavior primarily for survival,
      and the owls equalized capture opportunities by attacking both patches equally.

PMID- 24669723
TI  - Flow, recruitment limitation, and the maintenance of diversity in marine benthic
      communities.
AB  - Many terrestrial and marine systems are open to immigration. As such, the
      delivery of reproductive propagules should play a substantial role in determining
      local diversity in many systems. Here we present the results of a two-year
      experimental manipulation of subtidal flow regimes and show that flow has a
      strong positive effect on the assembly and maintenance of epifaunal invertebrate
      diversity by reducing recruitment limitation in two biogeographic regions. At two
      sites each in Alaska and Maine, USA, we experimentally manipulated flow speeds
      and measured the diversity of communities assembling through time and on
      recruitment panels scraped clean regularly. At all sites, the species richness of
      established communities, and the richness of recruitment into established
      communities and onto empty plates was >25% higher in enhanced flow than in
      control flow treatments. These effects were consistent for two years, and
      community diversity remained higher despite 30% higher species loss in enhanced
      flow treatments. Because communities remained open to immigration throughout the
      experiment, the data suggest that the diversity of epifaunal communities is
      strongly limited by recruitment and that supply-side effects on diversity in
      natural communities are strong. The positive effect of flow on diversity through
      a decrease in recruitment limitation was robust across scale, biogeographic
      region, and flow velocities and was consistent in magnitude in communities and on
      recruitment plates. Consequently, the data strongly suggest that the positive
      effects of flow on epifaunal diversity are persistent, can operate without
      diversity-enhancing positive feedback mechanisms, and are driven by increases in
      propagule delivery. Thus flow plays a large role in establishing and maintaining
      epifaunal diversity by mediating the delivery of propagules necessary to colonize
      a patch or to replace species within communities. Although our data do not
      preclude effects of interspecific interactions, they strongly suggest that flow
      plays a large and essentially untested role in determining the diversity of
      benthic marine communities, and they imply that flow is a key mechanism driving
      recruitment limitation in diverse aquatic systems.

PMID- 24669724
TI  - A new perspective on trait differences between native and invasive exotic plants.
AB  - Functional differences between native and exotic species potentially constitute
      one factor responsible for plant invasion. Differences in trait values between
      native and exotic invasive species, however, should not be considered fixed and
      may depend on the context of the comparison. Furthermore, the magnitude of
      difference between native and exotic species necessary to trigger invasion is
      unknown. We propose a criterion that differences in trait values between a native
      and exotic invasive species must be greater than differences between co-occurring
      natives for this difference to be ecologically meaningful and a contributing
      factor to plant invasion. We used a meta-analysis to quantify the difference
      between native and exotic invasive species for various traits examined in
      previous studies and compared this value to differences among native species
      reported in the same studies. The effect size between native and exotic invasive
      species was similar to the effect size between co-occurring natives except for
      studies conducted in the field; in most instances, our criterion was not met
      although overall differences between native and exotic invasive species were
      slightly larger than differences between natives. Consequently, trait differences
      may be important in certain contexts, but other mechanisms of invasion are likely
      more important in most cases. We suggest that using trait values as predictors of
      invasion will be challenging.

PMID- 24669725
TI  - Testing the competition-colonization trade-off with a 32-year study of a
      saxicolous lichen community.
AB  - Competition-colonization trade-offs are theorized to be a mechanism of
      coexistence in communities structured by environmental fluctuations. But many
      studies that have tested for the trade-off have failed to detect it, likely
      because a spatiotemporally structured environment and many species assemblages
      are needed to adequately test for a competition-colonization trade-off. Here, we
      present a unique 32-year study of rock-dwelling lichens in New Mexico, USA, in
      which photographs were used to quantify lichen life history traits and
      interactions through time. These data allowed us to determine whether there were
      any trade-offs between traits associated with colonization and competition, as
      well as the relationship between diversity and disturbance in the community. We
      did not find evidence for a trade-off between competitive ability and
      colonization rate or any related life history traits. Interestingly, we did find
      a peak in all measures of species diversity at intermediate levels of
      disturbance, consistent with the intermediate disturbance hypothesis pattern. We
      suggest that the coexistence of the dominant species in this system is regulated
      by differences in persistence and growth rate mediating overgrowth competition
      rather than a competition-colonization trade-off.

PMID- 24669726
TI  - Patch definition in metapopulation analysis: a graph theory approach to solve the
      mega-patch problem.
AB  - The manner in which patches are delineated in spatially realistic metapopulation
      models will influence the size, connectivity, and extinction and recolonization
      dynamics of those patches. Most commonly used patch-definition methods focus on
      identifying discrete, contiguous patches of habitat from a single temporal
      observation of species occurrence or from a model of habitat suitability.
      However, these approaches are not suitable for many metapopulation systems where
      entire patches may not be fully colonized at a given time. For these
      metapopulation systems, a single large patch of habitat may actually support
      multiple, interacting subpopulations. The interactions among these subpopulations
      will be ignored if the patch is treated as a single unit, a situation we term the
      "mega-patch problem." Mega-patches are characterized by variable intra-patch
      synchrony, artificially low inter-patch connectivity, and low extinction rates.
      One way to detect this problem is by using time series data to calculate
      demographic synchrony within mega-patches. We present a framework for identifying
      subpopulations in mega-patches using a combination of spatial autocorrelation and
      graph theory analyses. We apply our approach to southern California giant kelp
      (Macrocystis pyrifera) forests using a new, long-term (27 years), satellite-based
      data set of giant kelp canopy biomass. We define metapopulation patches using our
      method as well as several other commonly used patch delineation methodologies and
      examine the colonization and extinction dynamics of the metapopulation under each
      approach. We find that the relationships between patch characteristics such as
      area and connectivity and the demographic processes of colonizations and
      extinctions vary among the different patch-definition methods. Our spatial
      analysis/graph-theoretic framework produces results that match theoretical
      expectations better than the other methods. This approach can be used to identify
      subpopulations in metapopulations where the distributions of organisms do not
      always reflect the distribution of suitable habitat.

PMID- 24669727
TI  - A Bayesian approach to identifying and compensating for model misspecification in
      population models.
AB  - State-space estimation methods are increasingly used in ecology to estimate
      productivity and abundance of natural populations while accounting for
      variability in both population dynamics and measurement processes. However,
      functional forms for population dynamics and density dependence often will not
      match the true biological process, and this may degrade the performance of state
      space methods. We therefore developed a Bayesian semiparametric state-space
      model, which uses a Gaussian process (GP) to approximate the population growth
      function. This offers two benefits for population modeling. First, it allows data
      to update a specified "prior" on the population growth function, while reverting
      to this prior when data are uninformative. Second, it allows variability in
      population dynamics to be decomposed into random errors around the population
      growth function ("process error") and errors due to the mismatch between the
      specified prior and estimated growth function ("model error"). We used simulation
      modeling to illustrate the utility of GP methods in state-space population
      dynamics models. Results confirmed that the GP model performs similarly to a
      conventional state-space model when either (1) the prior matches the true process
      or (2) data are relatively uninformative. However, GP methods improve estimates
      of the population growth function when the function is misspecified. Results also
      demonstrated that the estimated magnitude of "model error" can be used to
      distinguish cases of model misspecification. We conclude with a discussion of the
      prospects for GP methods in other state-space models, including age and length
      structured, meta-analytic, and individual-movement models.

PMID- 24669728
TI  - Carbon accumulation and nitrogen pool recovery during transitions from savanna to
      forest in central Brazil.
AB  - The expansion of tropical forest into savanna may potentially be a large carbon
      sink, but little is known about the patterns of carbon sequestration during
      transitional forest formation. Moreover, it is unclear how nutrient limitation,
      due to extended exposure to fire-driven nutrient losses, may constrain carbon
      accumulation. Here, we sampled plots that spanned a woody biomass gradient from
      savanna to transitional forest in response to differential fire protection in
      central Brazil. These plots were used to investigate how the process of
      transitional forest formation affects the size and distribution of carbon (C) and
      nitrogen (N) pools. This was paired with a detailed analysis of the nitrogen
      cycle to explore possible connections between carbon accumulation and nitrogen
      limitation. An analysis of carbon pools in the vegetation, upper soil, and litter
      shows that the transition from savanna to transitional forest can result in a
      fourfold increase in total carbon (from 43 to 179 Mg C/ha) with a doubling of
      carbon stocks in the litter and soil layers. Total nitrogen in the litter and
      soil layers increased with forest development in both the bulk (+68%) and plant
      available (+150%) pools, with the most pronounced changes occurring in the upper
      layers. However, the analyses of nitrate concentrations, nitrate:ammonium ratios,
      plant stoichiometry of carbon and nitrogen, and soil and foliar nitrogen isotope
      ratios suggest that a conservative nitrogen cycle persists throughout forest
      development, indicating that nitrogen remains in low supply relative to demand.
      Furthermore, the lack of variation in underlying soil type (>20 cm depth)
      suggests that the biogeochemical trends across the gradient are driven by
      vegetation. Our results provide evidence for high carbon sequestration potential
      with forest encroachment on savanna, but nitrogen limitation may play a large and
      persistent role in governing carbon sequestration in savannas or other equally
      fire-disturbed tropical landscapes. In turn, the link between forest development
      and nitrogen pool recovery creates a framework for evaluating potential positive
      feedbacks on savanna-forest boundaries.

PMID- 24669729
TI  - Linking size-dependent growth and mortality with architectural traits across 145
      co-occurring tropical tree species.
AB  - Tree architecture, growth, and mortality change with increasing tree size and
      associated light conditions. To date, few studies have quantified how size
      dependent changes in growth and mortality rates co-vary with architectural
      traits, and how such size-dependent changes differ across species and possible
      light capture strategies. We applied a hierarchical Bayesian model to quantify
      size-dependent changes in demographic rates and correlated demographic rates and
      architectural traits for 145 co-occurring Malaysian rain-forest tree species
      covering a wide range of tree sizes. Demographic rates were estimated using
      relative growth rate in stem diameter (RGR) and mortality rate as a function of
      stem diameter. Architectural traits examined were adult stature measured as the
      95-percentile of the maximum stem diameter (upper diameter), wood density, and
      three tree architectural variables: tree height, foliage height, and crown width.
      Correlations between demographic rates and architectural traits were examined for
      stem diameters ranging from 1 to 47 cm. As a result, RGR and mortality varied
      significantly with increasing stem diameter across species. At smaller stem
      diameters, RGR was higher for tall trees with wide crowns, large upper diameter,
      and low wood density. Increased mortality was associated with low wood density at
      small diameters, and associated with small upper diameter and wide crowns over a
      wide range of stem diameters. Positive correlations between RGR and mortality
      were found over the whole range of stem diameters, but they were significant only
      at small stem diameters. Associations between architectural traits and
      demographic rates were strongest at small stem diameters. In the dark understory
      of tropical rain forests, the limiting amount of light is likely to make the
      interspecific difference in the effects of functional traits on demography more
      clear. Demographic performance is therefore tightly linked with architectural
      traits such as adult stature, wood density, and capacity for horizontal crown
      expansion. The enhancement of a demographic trade-off due to interspecific
      variation in functional traits in the understory helps to explain species
      coexistence in diverse rain forests.

PMID- 24669730
TI  - Integrated assessment of the direct and indirect effects of resource gradients on
      tree species recruitment.
AB  - Understanding the dynamics of tree establishment is critical to assess forests'
      composition, management practices, and current responses to global change. We
      carried out a field seedling transplant experiment to assess not only the direct
      effects of resources influencing recruitment of four tree species, but also their
      indirect and combined effects. Our analysis integrated first growing season
      demographic data together with estimates of mycorrhizal fungal colonization and
      resource availability (light, soil moisture, and soil nitrogen). Only by
      considering both the direct and indirect effects of resources we were able to
      account for most of the variability observed during seedling recruitment.
      Contrary to expectations, increasing light levels were not always beneficial for
      recruitment even in low light habitats, and soil moisture availability benefited
      seedling growth but not survival. In addition, mycorrhizal fungal colonization
      was not always favored by high light levels or by increasing soil moisture.
      Seedling survival for all species was lower in plots with higher arbuscular
      mycorrhizal fungi, while the association with ectomycorrhizal fungi varied from
      beneficial to detrimental. When integrating the direct, indirect, and interactive
      effects of resource availability and mycorrhizal fungal colonization on tree
      recruitment dynamics we found that species responded in a nonlinear fashion to
      increasing resource levels, and we also identified thresholds, i.e., shifts in
      the direction of the response, along the resource gradient. Our integrated
      assessment considerably outperformed a null model where only direct effects of
      resources were accounted for. These results illustrate how the combination of
      direct, indirect, and combined effects of driving variables better represents the
      complexity of the processes determining tree species recruitment than simple
      resource availability mechanisms.

PMID- 24669731
TI  - Effect of spatial processes and topography on structuring species assemblages in
      a Sri Lankan dipterocarp forest.
AB  - Niche and neutral theories emphasize different processes that contribute to the
      maintenance of species diversity and should leave different spatial structures in
      species assemblages. In this study we used variation partitioning in combination
      with distance-based Moran's eigenvector maps and habitat variables to determine
      the relative importance of the effects of pure habitat, pure spatial, and
      spatially structured habitat processes on the spatial distribution of tree
      species composition and richness in a 25-ha tropical rain forest of Sinharaja/Sri
      Lanka. We analyzed the contribution of those components at three spatial scales
      (10 m, 20 m, and 50 m) for all trees and the three life stages: recruits,
      juveniles, and adults. At the 10-m scale, 80% of the variation in species
      composition remained unexplained for recruits and adults, but only 55% for
      juveniles. With increasingly broader scales these figures were strongly reduced,
      mainly by an increasing contribution of the spatially structured habitat
      component, which explained 4-30%, 20-47%, and 8-35% of variation in species
      composition for recruits, juveniles, and adults, respectively. The pure spatial
      component was most important at the 20-m scale and reached 20%, 32%, and 23% for
      recruits, juveniles, and adults, respectively. The spatially structured habitat
      component described variability at broader scales than the pure spatial
      component. Our results suggest that stochastic processes and spatially
      structuring processes of community dynamics, such as dispersal limitation and
      habitat association, contributed jointly to explain species composition and
      richness at the Sinharaja forest, but their relative importance changed with
      scale and life stage. Species assembly at the local scale was more strongly
      impacted by stochasticity, whereas the signal of habitat was stronger at the 50-m
      scale where plant-scale stochasticity is averaged out. Recent research points to
      an emerging consensus on the relative contribution of stochasticity, habitat, and
      spatial processes in governing community assembly, but how these components
      change with life stage, and how this is influenced by sample size, remains to be
      explored.

PMID- 24669732
TI  - Genetic variation within a dominant shrub structures green and brown community
      assemblages.
AB  - Two rising challenges in ecology are understanding the linkages between above-
      and belowground components of terrestrial ecosystems and connecting genes to
      their ecological consequences. Here, we blend these emerging perspectives using a
      long-term common-garden experiment in a coastal dune ecosystem, whose dominant
      shrub species, Baccharis pilularis, exists as erect or prostrate architectural
      morphotypes. We explored variation in green (foliage-based) and brown (detritus
      based) community assemblages, local ecosystem processes, and understory
      microclimate between the two morphs. Prostrate morphs supported more individuals,
      species, and different compositions of foliage arthropods, litter
      microarthropods, and soil bacteria than erect morphs. The magnitude of community
      compositional differences was maintained from crown to litter to soil. Despite
      showing strikingly similar responses, green and brown assemblages were associated
      with different underlying mechanisms. Differences in estimated shrub biomass best
      explained variation in the green assemblage, while understory abiotic conditions
      accounted for variation in the brown assemblage. Prostrate morphs produced more
      biomass and litter, which corresponded with their strong lateral growth in a
      windy environment. Compared to erect morphs, the denser canopy and thicker litter
      layer of prostrate morphs helped create more humid understory conditions. As a
      result, decomposition rates were higher under prostrate shrubs, despite prostrate
      litter being of poorer quality. Together, our results support the hypothesis that
      intraspecific genetic variation in primary producers is a key mediator of above-
      and belowground linkages, and that integrating the two perspectives can lead to
      new insights into how terrestrial communities are linked with ecosystem pools and
      processes.

PMID- 24669733
TI  - Specific leaf area responses to environmental gradients through space and time.
AB  - Plant communities can respond to environmental changes by altering their species
      composition and by individuals (within species) adjusting their physiology. These
      responses can be captured by measuring key functional traits among and within
      species along important environmental gradients. Some anthropogenic changes (such
      as fertilizer runoff) are known to induce distinct community responses, but
      rarely have responses across natural and anthropogenic gradients been compared in
      the same system. In this study, we used comprehensive specific leaf area (SLA)
      data from a diverse Australian annual plant system to examine how individual
      species and whole communities respond to natural and anthropogenic gradients, and
      to climatically different growing seasons. We also investigated the influence of
      different leaf-sampling strategies on community-level results. Many species had
      similar mean SLA values but differed in SLA responses to spatial and temporal
      environmental variation. At the community scale, we identified distinct SLA
      responses to natural and anthropogenic gradients. Along anthropogenic gradients,
      increased mean SLA, coupled with SLA convergence, revealed evidence of
      competitive exclusion. This was further supported by the dominance of species
      turnover (vs. intraspecific variation) along these gradients. We also revealed
      strong temporal changes in SLA distributions in response to increasing growing
      season precipitation. These climate-driven changes highlight differences among co
      occurring species in their adaptive capacity to exploit abundant water resources
      during favorable seasons, differences that are likely to be important for species
      coexistence in this system. In relation to leaf-sampling strategies, we found
      that using leaves from a climatically different growing season can lead to
      misleading conclusions at the community scale.

PMID- 24669734
TI  - Turf wars: experimental tests for alternative stable states in a two-phase
      coastal ecosystem.
AB  - Alternative stable states have long been thought to exist in natural communities,
      but direct evidence for their presence and for the environmental switches that
      cause them has been scarce. Using a combination of greenhouse and field
      experiments, we investigated the environmental drivers associated with two
      distinctive herbaceous communities in coastal ecosystems in New Zealand. In a
      mosaic unrelated to micro-topography, a community dominated largely by native
      turf species (notably Leptinella dioica, Samolus repens, and Selliera radicans)
      alternates with vegetation comprising exotic (i.e., nonnative) pasture species
      (notably Agrostis stolonifera, Holcus lanatus, Lolium perenne, and Trifolium
      repens). The species of these two communities differ in functional characters
      related to leaf longevity and growth rate, and occupy soils of differing nitrogen
      levels. Both spatial and environmental factors influenced the species composition
      locally. Reciprocal transplants of soil, with and without associated vegetation,
      showed that a native turf community developed when sward or soil from either
      community was bounded by turf, and a pasture community developed when sward or
      soil from either community was surrounded by pasture. In artificial mixed
      communities in the greenhouse, turf was able to invade the pasture community
      where the vegetation was clipped to simulate grazing, and also where Trifolium
      was removed and/or salt spray was applied. The pasture community invaded the turf
      where Trifolium was present or nitrogen was added. These results were supported
      by trends in experimentally manipulated field plots, where the amount of turf
      cover increased when nitrogen was kept low and when salt spray was applied,
      whereas pasture cover increased in the absence of salt spray. Thus, persistence
      of the native turf community is dependent on grazing, both directly and via its
      effect on keeping nitrogen levels low by excluding the exotic, nitrogen-fixing
      Trifolium, and by exposing the vegetation to salt spray. If any of these factors
      change, there could be a state change to pasture dominance that might be
      resistant to reversion to turf. Managing such coastal herbaceous communities
      therefore requires an understanding of the environmental and species
      characteristics that maintain alternative states.

PMID- 24669735
TI  - Intra-annual rainfall regime shifts competitive interactions between coastal sage
      scrub and invasive grasses.
AB  - Changes in rainfall distribution, generally predicted by many climate models, can
      affect resource dynamics and ecosystem function. While little studied, intra
      annual rainfall distribution may have particularly strong effects on competitive
      interactions. Here, we test whether increased rainfall event size and decreased
      frequency within a growing season can influence competitive dynamics related to
      the invasion of exotic annual grasses in California coastal sage scrub (CSS). We
      hypothesized that larger rainfall events and decreased frequency will increase
      the competitive ability of native CSS species: a deeper root system will permit
      greater water use during dry periods between pulses and enhance their resource
      depletion effect on more shallow-rooted grasses. We planted grass and CSS
      seedlings in an additive competition design under three rainfall treatments:
      frequent small events, infrequent large events, and infrequent small events. The
      first two treatments had the same total rainfall but different frequency, while
      the second and third treatments had the same frequency but different total
      rainfall. Rainfall treatment altered the competitive interactions between CSS and
      grasses. In the first year, the competitive effect of annual grasses on shrub
      seedlings was strongest under the frequent small rainfall regime where they
      reduced deep soil moisture and light. In year two, the established shrubs began
      to exert strong competitive effects on grasses, and these effects were strongest
      under the infrequent small rainfall regime (low total rain) where they reduced
      shallow soil moisture and decreased grass stomatal conductance. Results suggest
      that reductions in both rainfall frequency and total rainfall may be important to
      competitive interactions, and can alter plant community composition and invasion
      when species have different rooting depths and different responses to soil
      moisture.

PMID- 24669736
TI  - Distinguishing individual quality from habitat preference and quality in a
      territorial passerine.
AB  - Theory predicts that animals breeding in heterogeneous landscapes preferentially
      occupy habitats likely to maximize individual fitness, but identifying those
      habitats has proved problematic. Many studies develop metrics of habitat quality
      linked to site-specific reproductive output measured in successive years, but few
      separate the independent effects of individual "intrinsic quality" from those due
      solely to the attributes of the habitats themselves. In many populations,
      processes such as competitive territory defense, longevity, site-fidelity, and
      variation in breeding density and territory size over time have the potential to
      limit the degree to which individual and habitat quality will be positively
      related in nature. However, the effects of these processes on estimates of
      habitat or site-specific reproductive output have not been thoroughly
      investigated. We show that, in an insular population of Song Sparrows (Melospiza
      melodia), females nested preferentially in breeding sites with high mean
      reproductive output assessed over 35 years, and that variation in site-specific
      reproductive output was positively related to female intrinsic quality, measured
      here as the lifetime reproductive success of individual females relative to
      others hatched the same year (rLRS). In contrast, vegetation traits (shrub cover,
      edge, and soil depth) predicted female preference for breeding sites but did not
      predict site-specific variation in annual reproductive output. Female quality
      also did not predict which females occupied more- or less-preferred breeding
      sites over the study period. However, mean annual reproductive output of breeding
      sites estimated over 35 years was strongly positively related to the quality of
      the females that nested in them. Overall, these results indicate that site
      specific estimates of habitat quality that do not consider the quality of the
      individuals occupying those sites may include substantial bias due to variation
      in occupant quality, and thus may not reliably predict the intrinsic effects of
      habitat quality on individual or population fitness.

PMID- 24669737
TI  - From recruitment to senescence: food shapes the age-dependent pattern of breeding
      performance in a long-lived bird.
AB  - We used a long-term data set (26 years) from Audouin's Gull (Larus audouinii), a
      long-lived seabird, to address the relationship between the age-dependent pattern
      of reproductive performance and environmental conditions during breeding.
      Although theoretical models predict that the youngest and oldest breeders (due to
      inexperience and senescence, respectively) will perform less well than
      intermediate age classes, few empirical data exist regarding how this expected
      pattern varies with food availability. To assess the influence of age and food
      availability (corrected by population size of the main consumers to take into
      account density dependence) on a number of breeding parameters (laying dates, egg
      volume, clutch size, and hatching success), we modeled mean and variances of
      these parameters by incorporating heterogeneity into generalized linear models.
      All parameters varied with age and to different degrees, depending on food
      availability. As expected, performance improved with increased food supply, and
      the observed age pattern was quadratic, with poorer breeding performances
      occurring in extreme ages. For most parameters (except for laying dates, for
      which age and food did not interact), the pattern changed with food somewhat
      unexpectedly; the differences in performance between age classes were higher
      (i.e., the quadratic pattern was more noticeable) when food was more readily
      available than when food availability was lower. We suggest that, under poor
      environmental conditions, only high-quality individuals of the younger and older
      birds bred and that the differences in breeding performance between age classes
      were smaller. Although variances for egg volume were constant, variances for
      laying dates were highest for the youngest breeders and tended to decrease with
      age, either due to the selection of higher-quality individuals or to a greater
      frequency of birds skipping breeding with age, especially when food was in low
      supply. Our results show that mean and variances of breeding parameters changed
      with age, but that this pattern was different for each parameter and also varied
      according to food availability. It is likely that, other than food, certain
      additional factors (e.g., sex, cohort effects, density dependence) also influence
      changes in breeding performance with age, and this may preclude the finding of a
      common pattern among traits and among studies on different taxa.

PMID- 24669739
TI  - Land-use impacts on plant-pollinator networks: interaction strength and
      specialization predict pollinator declines.
AB  - Land use is known to reduce the diversity of species and complexity of biotic
      interactions. In theory, interaction networks can be used to predict the
      sensitivity of species against co-extinction, but this has rarely been applied to
      real ecosystems facing variable land-use impacts. We investigated plant
      pollinator networks on 119 grasslands that varied quantitatively in management
      regime, yielding 25401 visits by 741 pollinator species on 166 plant species.
      Species-specific plant and pollinator responses to land use were significantly
      predicted by the weighted average land-use response of each species' partners.
      Moreover, more specialized pollinators were more vulnerable than generalists.
      Both predictions are based on the relative interaction strengths provided by the
      observed interaction network. Losses in flower and pollinator diversity were
      linked, and mutual dependence between plants and pollinators accelerates the
      observed parallel declines in response to land-use intensification. Our findings
      confirm that ecological networks help to predict natural community responses to
      disturbance and possible secondary extinctions.

PMID- 24669738
TI  - Invasive plant erodes local song diversity in a migratory passerine.
AB  - Exotic plant invasions threaten ecosystems globally, but we still know little
      about the specific consequences for animals. Invasive plants can alter the
      quality of breeding habitat for songbirds, thereby impacting important
      demographic traits such as dispersal, philopatry, and age structure. These
      demographic effects may in turn alter song-learning conditions to affect song
      structure and diversity. We studied Chipping Sparrows (Spizella passerina)
      breeding in six savannas that were either dominated by native vegetation or
      invaded by spotted knapweed (Centaurea stoebe), an exotic forb known to diminish
      food resources and reproductive success. Here, we report that the prevalence of
      older birds was relatively low in knapweed-invaded habitat, where recruitment of
      yearlings compensated for diminished site fidelity to sustain territory
      abundance. In both habitat types, yearling males tended to adopt songs similar to
      their neighbors and match the songs of older birds rather than introducing new
      song types, a pattern seen in many songbird species. As a consequence, in invaded
      habitat where age structure was skewed away from older birds serving as potential
      song models, yearlings converged on fewer song types. Similarity of songs among
      individuals was significantly higher and the overall number of song types
      averaged nearly 20% lower in invaded relative to native habitat. Degradation of
      habitat quality generally impacts site fidelity and age ratios in migratory
      songbirds and hence may commonly alter song-learning conditions. Associated
      shifts in song attributes known to influence reproductive success could in turn
      enforce demographic declines driven by habitat degradation. Local song structure
      may serve as an important indicator of habitat quality and population status for
      songbirds.

PMID- 24669740
TI  - The structure of ant-plant ecological networks: is abundance enough?
AB  - Knowledge of the mechanisms that shape biodiversity is essential to understand
      the ecological and evolutionary dynamics of interacting species. Recent studies
      posit that most of the organization of mutualistic networks is shaped by
      differences in species abundance among interacting species. In this study, we
      examined the mutualism involving plants with extrafloral nectaries and their
      associated ants. We show empirically that the difference in abundance among ants
      on vegetation partially explains the network structure of mutualistic
      interactions and that it is independent of ant species compositions: an ant
      species that is abundant usually interacts with more plant species. Moreover,
      nested networks are generated by simple variation in ant abundance on foliage.
      However, in ant-plant mutualistic networks, nestedness was higher than in
      networks describing the occurrence of ants on plants without a food resource.
      Additionally, the plant and ant species with the highest number of interactions
      within these networks interacted more among themselves than expected under the
      assumption of an abundance-based, random mixing of individuals. We hypothesize
      that the dominance of these ant species occurs because these ants are able to
      outcompete other ant species when feeding on extrafloral nectaries and because of
      the presence of ecophysiological adaptations to utilize liquid food.

PMID- 24669741
TI  - Species interactions and a chain of indirect effects driven by reduced
      precipitation.
AB  - Climate change can affect species directly and indirectly by altering
      interactions between species within communities. These indirect effects can
      ramify through a community and affect many species, including some that may not
      have been directly affected by the perturbation. Identifying these chains of
      indirect effects is difficult, and most studies only follow indirect effects
      across two or three species. Here, we use a factorial field experiment to
      demonstrate that precipitation affects spotted aphids through a complex chain of
      indirect interactions that are mediated by other herbivores and a generalist
      predator. We experimentally simulated drought, which reduced water content in
      alfalfa plants. While water stress in alfalfa had no direct effect on spotted
      aphids, it lowered the population growth rate of pea aphids, another common
      alfalfa pest. Because ladybeetle predators were attracted to high pea aphid
      densities, predator densities were lower in drought treatments. Consequently,
      spotted aphid densities were released from top-down control (apparent
      competition) in drought treatments and reached densities three times higher than
      spotted aphids in ambient treatments with high pea aphid densities. Thus, drought
      affected spotted aphids in the interaction chain: drought --> alfalfa --> pea
      aphids --> predators --> spotted aphids. This result illustrates the lengthy path
      that indirect effects of climate change may take through a community, as well as
      the importance of community-level experiments in determining the net effect of
      climate change.

PMID- 24669742
TI  - Environmental context influences both the intensity of seed predation and plant
      demographic sensitivity to attack.
AB  - Variation in mutualistic and antagonistic interactions are important sources of
      variation in population dynamics and natural selection. Environmental
      heterogeneity can influence the outcome of interactions by affecting the
      intensity of interactions, but also by affecting the demography of the
      populations involved. However, little is known about the relative importance of
      environmental effects on interaction intensities and demographic sensitivity for
      variation in population growth rates. We investigated how soil depth, soil
      moisture, soil nutrient composition, and vegetation height influenced the
      intensity of seed predation as well as host plant demography and sensitivity to
      seed predation in the perennial herb Primula farinosa. Intensity of seed
      predation ranged from 0% to 80% of seeds damaged among the 24 study populations
      and was related to soil moisture in two of four years. The effect of seed
      predation on plant population growth rate (lambda) ranged from negligible to a
      reduction in lambda by 0.70. Sensitivity of population growth rate to predation
      explained as much of the variation in the reductions in population growth rate
      due to seed predation as did predation intensity. Plant population growth rate in
      the absence of seed predation and sensitivity to predation were negatively
      related to soil depth and soil moisture. Both intensity of predation and
      sensitivity to predation were positively correlated with potential population
      growth rate and, as a result, there was no significant relationship between
      predation intensity and realized population growth rate. We conclude that in our
      study system environmental context influences the effects of seed predation on
      plant fitness and population dynamics in two important ways: through variation in
      interaction intensity and through sensitivity to the effects of this interaction.
      Moreover, our results show that a given abiotic factor can influence population
      growth rate in different directions through effects on potential growth rate,
      intensity of biotic interactions, and the sensitivity of population growth rate
      to interactions.

PMID- 24669743
TI  - Predicting species' maximum dispersal distances from simple plant traits.
AB  - Many studies have shown plant species' dispersal distances to be strongly related
      to life-history traits, but how well different traits can predict dispersal
      distances is not yet known. We used cross-validation techniques and a global data
      set (576 plant species) to measure the predictive power of simple plant traits to
      estimate species' maximum dispersal distances. Including dispersal syndrome
      (wind, animal, ant, ballistic, and no special syndrome), growth form (tree,
      shrub, herb), seed mass, seed release height, and terminal velocity in different
      combinations as explanatory variables we constructed models to explain variation
      in measured maximum dispersal distances and evaluated their power to predict
      maximum dispersal distances. Predictions are more accurate, but also limited to a
      particular set of species, if data on more specific traits, such as terminal
      velocity, are available. The best model (R2 = 0.60) included dispersal syndrome,
      growth form, and terminal velocity as fixed effects. Reasonable predictions of
      maximum dispersal distance (R2 = 0.53) are also possible when using only the
      simplest and most commonly measured traits; dispersal syndrome and growth form
      together with species taxonomy data. We provide a function (dispeRsal) to be run
      in the software package R. This enables researchers to estimate maximum dispersal
      distances with confidence intervals for plant species using measured traits as
      predictors. Easily obtainable trait data, such as dispersal syndrome (inferred
      from seed morphology) and growth form, enable predictions to be made for a large
      number of species.

PMID- 24669744
TI  - Hierarchical mechanisms of spatially contagious seed dispersal in complex seed
      disperser networks.
AB  - Intra- and interspecific spatially contagious seed dispersal has far-reaching
      implications for plant recruitment, distribution, and community assemblage.
      However, logistical and analytical limitations have curtailed our understanding
      concerning the mechanisms and resulting spatial patterns of contagious seed
      dispersal in most systems and, especially, in complex seed-disperser networks. We
      investigated mechanisms of seed aggregation using techniques of spatial point
      pattern analysis and extensive data sets on mutispecific endozoochorous seed rain
      generated by five frugivorous mammals in three Mediterranean shrublands over two
      seasons. Our novel analytical approach revealed three hierarchical and
      complementary mechanisms of seed aggregation acting at different levels (fecal
      samples, seeds, pairs of seed species) and spatial scales. First, the three local
      guilds of frugivores tended to deliver their feces highly aggregated at small and
      intermediate spatial scales, and the overall pattern of fecal delivery could be
      described well by a nested double-cluster Thomas process. Second, once the strong
      observed fecal aggregation was accounted for, the distribution of mammal feces
      containing seeds was clustered within the pattern of all feces (i.e., with and
      without seeds), and the density of fecal samples containing seeds was higher than
      expected around other feces containing seeds in two out of the three studied seed
      disperser networks. Finally, at a finer level, mark correlation analyses revealed
      that for some plant species pairs, the number of dispersed seeds was positively
      associated either at small or large spatial scales. Despite the relatively
      invariant patterning of nested double-clustering, some attributes of
      endozoochorous seed rain (e.g., intensity, scales of aggregation) were variable
      among study sites due to changes in the ecological context in which seeds and
      their dispersers interact. Our investigation disentangles for the first time the
      hierarchy of synergic mechanisms of spatially contagious seed dispersal at a
      range of spatial scales in complex seed-disperser networks, thus providing a
      robust and widely applicable framework for future studies.

PMID- 24669745
TI  - Lack of energetic equivalence in forest soil invertebrates.
AB  - Ecological communities consist of small abundant and large non-abundant species.
      The energetic equivalence rule is an often-observed pattern that could be
      explained by equal energy usage among abundant small organisms and non-abundant
      large organisms. To generate this pattern, metabolism (as an indicator of
      individual energy use) and abundance have to scale inversely with body mass, and
      cancel each other out. In contrast, the pattern referred to as biomass
      equivalence states that the biomass of all species in an area should be constant
      across the body-mass range. In this study, we investigated forest soil
      communities with respect to metabolism, abundance, population energy use, and
      biomass. We focused on four land-use types in three different landscape blocks
      (Biodiversity Exploratories). The soil samples contained 870 species across 12
      phylogenetic groups. Our results indicated positive sublinear metabolic scaling
      and negative sublinear abundance scaling with species body mass. The
      relationships varied mainly due to differences among phylogenetic groups or
      feeding types, and only marginally due to land-use type. However, these scaling
      relationships were not exactly inverse to each other, resulting in increasing
      population energy use and biomass with increasing body mass for most combinations
      of phylogenetic group or feeding type with land-use type. Thus, our results are
      mostly inconsistent with the classic perception of energetic equivalence, and
      reject the biomass equivalence hypothesis while documenting a specific and
      nonrandom pattern of how abundance, energy use, and biomass are distributed
      across size classes. However, these patterns are consistent with two alternative
      predictions: the resource-thinning hypothesis, which states that abundance
      decreases with trophic level, and the allometric degree hypothesis, which states
      that population energy use should increase with population average body mass, due
      to correlations with the number of links of consumers and resources. Overall, our
      results suggest that a synthesis of food web structures with metabolic theory may
      be most promising for predicting natural patterns of abundance, biomass, and
      energy use.

PMID- 24669746
TI  - Lake morphometry and resource polymorphism determine niche segregation between
      cool- and cold-water-adapted fish.
AB  - Climate change is increasing ambient temperatures in Arctic and subarctic
      regions, facilitating latitudinal range expansions of freshwater fishes adapted
      to warmer water temperatures. The relative roles of resource availability and
      interspecific interactions between resident and invading species in determining
      the outcomes of such expansions has not been adequately evaluated. Ecological
      interactions between a cool-water adapted fish, the perch (Perca fluviatilis),
      and the cold-water adapted European whitefish (Coregonus lavaretus), were studied
      in both shallow and deep lakes with fish communities dominated by (1) monomorphic
      whitefish, (2) monomorphic whitefish and perch, and (3) polymorphic whitefish and
      perch. A combination of stomach content, stable-isotope, and invertebrate prey
      availability data were used to identify resource use and niche overlap among
      perch, the trophic generalist large sparsely rakered (LSR) whitefish morph, and
      the pelagic specialist densely rakered (DR) whitefish morph in 10 subarctic lakes
      at the contemporary distribution limit of perch in northern Scandinavia. Perch
      utilized its putative preferred littoral niche in all lakes. LSR whitefish
      utilized both littoral and pelagic resources in monomorphic whitefish-dominated
      lakes. When found in sympatry with perch, LSR whitefish exclusively utilized
      pelagic prey in deep lakes, but displayed niche overlap with perch in shallow
      littoral lakes. DR whitefish was a specialist zooplanktivore, relegating LSR
      whitefish from pelagic habitats, leading to an increase in niche overlap between
      LSR whitefish and perch in deep lakes. Our results highlight how resource
      availability (lake depth and fish community) governs ecological interactions
      between native and invading species, leading to different outcomes even at the
      same latitudes. These findings suggest that lake morphometry and fish community
      structure data should be included in bioclimate envelope-based models of species
      distribution shifts following predicted climate change.

PMID- 24669747
TI  - The metabolic theory of ecology convincingly explains the latitudinal diversity
      gradient of neotropical freshwater fish.
AB  - In the context of diversity gradients, the metabolic theory of ecology (MTE)
      posits that the logarithm of species richness should decrease linearly with the
      inverse of temperature, resulting in a specific slope. However, the empirical
      validity of this model depends on whether the data do not violate certain
      assumptions. Here, we test the predictions of MTE evaluating all of its
      assumptions simultaneously. We used Neotropical freshwater fish and tested
      whether the logarithm of species richness varied negatively and linearly with
      temperature, resulting in the slope value specified by the MTE. As we observed
      that the assumption of the energetic equivalence of populations was not achieved,
      we also analyzed whether the energetic nonequivalence of populations could be
      responsible for the possible lack of fit to the MTE predictions. Our results
      showed that the relationship between richness and the inverse of temperature was
      linear, negative and significant and included the slope value predicted by the
      MTE. With respect to the assumptions, we observed that there was no spatial
      variation in the average energy flux of populations or in the body size and
      abundance of species. However, the energetic equivalence of populations was not
      achieved and the violation of this assumption did not affect the predictive power
      of the model. We conclude that the validity of the assumptions (spatial
      invariance in the average flux energy of populations and spatial invariance in
      the body size and abundance, especially) is required for the correct
      interpretation of richness patterns. Furthermore, we conclude that MTE is robust
      in its explanation of diversity gradients for freshwater fish, proving to be a
      valuable tool in describing ecological complexity from individuals to ecosystems.

PMID- 24669748
TI  - Differing Daphnia magna assimilation efficiencies for terrestrial, bacterial, and
      algal carbon and fatty acids.
AB  - There is considerable interest in the pathways by which carbon and growth
      limiting elemental and biochemical nutrients are supplied to upper trophic
      levels. Fatty acids and sterols are among the most important molecules
      transferred across the plant-animal interface of food webs. In lake ecosystems,
      in addition to phytoplankton, bacteria and terrestrial organic matter are
      potential trophic resources for zooplankton, especially in those receiving high
      terrestrial organic matter inputs. We therefore tested carbon, nitrogen, and
      fatty acid assimilation by the crustacean Daphnia magna when consuming these
      resources. We fed Daphnia with monospecific diets of high-quality (Cryptomonas
      marssonii) and intermediate-quality (Chlamydomonas sp. and Scenedesmus gracilis)
      phytoplankton species, two heterotrophic bacterial strains, and particles from
      the globally dispersed riparian grass, Phragmites australis, representing
      terrestrial particulate organic carbon (t-POC). We also fed Daphnia with various
      mixed diets, and compared Daphnia fatty acid, carbon, and nitrogen assimilation
      across treatments. Our results suggest that bacteria were nutritionally
      inadequate diets because they lacked sterols and polyunsaturated omega-3 and
      omega-6 (omega-3 and omega-6) fatty acids (PUFAs). However, Daphnia were able to
      effectively use carbon and nitrogen from Actinobacteria, if their basal needs for
      essential fatty acids and sterols were met by phytoplankton. In contrast to
      bacteria, t-POC contained sterols and omega-6 and omega-3 fatty acids, but only
      at 22%, 1.4%, and 0.2% of phytoplankton levels, respectively, which indicated
      that t-POC food quality was especially restricted with regard to omega-3 PUFAs.
      Our results also showed higher assimilation of carbon than fatty acids from t-POC
      and bacteria into Daphnia, based on stable-isotope and fatty acids analysis,
      respectively. A relatively high (>20%) assimilation of carbon and fatty acids
      from t-POC was observed only when the proportion of t-POC was >60%, but due to
      low PUFA to carbon ratio, these conditions yielded poor Daphnia growth. Because
      of lower assimilation for carbon, nitrogen, and fatty acids from t-POC relative
      to diets of bacteria mixed with phytoplankton, we conclude that the microbial
      food web, supported by phytoplankton, and not direct t-POC consumption, may
      support zooplankton production. Our results suggest that terrestrial particulate
      organic carbon poorly supports upper trophic levels of the lakes.

PMID- 24669749
TI  - Dependence of the absorption and optical surface plasmon scattering of MoS2
      nanoparticles on aspect ratio, size, and media.
AB  - The optical and electronic properties of suspensions of inorganic fullerene-like
      nanoparticles of MoS2 are studied through light absorption and zeta-potential
      measurements and compared to those of the corresponding microscopic platelets.
      The total extinction measurements show that, in addition to excitonic peaks and
      the indirect band gap transition, a new peak is observed at 700-800 nm. This
      spectral peak has not been reported previously for MoS2. Comparison of the total
      extinction and decoupled absorption spectrum indicates that this peak largely
      originates from scattering. Furthermore, the dependence of this peak on
      nanoparticle size, shape, and surface charge, as well as solvent refractive
      index, suggests that this transition arises from a plasmon resonance. 

PMID- 24669752
TI  - Mixed matrix membranes with strengthened MOFs/polymer interfacial interaction and
      improved membrane performance.
AB  - MOFs-based mixed matrix membranes (MMMs) have attracted extensive attention in
      recent years due to their potential high separation performance, the low cost,
      and good mechanical properties. However, it is still very challenging to achieve
      defect-free interface between micrometer-sized MOFs and a polymer matrix. In this
      study, [Cd2L(H2O)]2.5H2O (Cd-6F) synthesized using 4,4'
      (hexafluoroisopropylidene)diphthalic anhydride (6FDA) as an organic ligand was
      introduced into the 6FDA-ODA polyimide matrix to achieve novel MOF MMMs. A
      specific interfacial interaction between MOF crystals and polymer chains was
      innovatively targeted and achieved through in situ polymerization procedure. The
      enhanced adhesion between MOF particles and polymer phase was observed, and the
      improved interfacial interaction between Cd-6F and the 6FDA-ODA polyimide matrix
      was confirmed by detailed characterizations including FTIR and NMR. In the
      meantime, the gas permeance and selectivity of the MMMs are strongly dependent on
      their morphology. The MMM derived from in situ polymerization presents excellent
      interfaces between micrometer-sized MOF crystals and the polymer matrix,
      resulting in increased permeability and selectivity. The strategy shown here can
      be further utilized to select the MOF/polymer pair, eliminate interfacial voids,
      and improve membrane separation performance of MOFs-based MMMs. 

PMID- 24669750
TI  - A pilot study comparing the effect of flaxseed, aromatase inhibitor, and the
      combination on breast tumor biomarkers.
AB  - Use of complementary approaches is common among breast cancer survivors.
      Potential interactions between aromatase inhibitors (AI) and high phytoestrogen
      foods, such as flaxseed (FS), are not often described. We conducted a pilot 2 * 2
      factorial, randomized intervention study between tumor biopsy and resection, in
      24 postmenopausal women with estrogen receptor positive (ER+) breast cancer, to
      assess the effects of FS and anastrozole, and possible interactions between them,
      on serum steroid hormone and tumor-related characteristics associated with long
      term survival (Roswell Park Cancer Institute, 2007-2010). The effect of each
      treatment vs. placebo on outcomes was determined by linear regression adjusting
      for pretreatment measure, stage, and grade. Although not statistically
      significant, mean ERbeta expression was approximately 40% lower from pre- to
      postintervention in the FS + AI group only. We observed a statistically
      significant negative association (beta +/- SE -0.3 +/- 0.1; P = 0.03) for
      androstenedione in the FS + AI group vs. placebo and for DHEA with AI treatment
      (beta +/- SE -1.6 +/- 0.6; P = 0.009). Enterolactone excretion was much lower in
      the FS + AI group compared to the FS group. Our results do not support strong
      effects of FS on AI activity for selected breast tumor characteristics or serum
      steroid hormone levels but suggest AI therapy might reduce the production of
      circulating mammalian lignans from FS. 

PMID- 24669751
TI  - Reaching the hard-to-reach: a systematic review of strategies for improving
      health and medical research with socially disadvantaged groups.
AB  - BACKGROUND: This study aims to review the literature regarding the barriers to
      sampling, recruitment, participation, and retention of members of
      socioeconomically disadvantaged groups in health research and strategies for
      increasing the amount of health research conducted with socially disadvantaged
      groups. METHODS: A systematic review with narrative synthesis was conducted.
      Searches of electronic databases Medline, PsychInfo, EMBASE, Social Science Index
      via Web of Knowledge and CINHAL were conducted for English language articles
      published up to May 2013. Qualitative and quantitative studies as well as
      literature reviews were included. Articles were included if they reported
      attempts to increase disadvantaged group participation in research, or the
      barriers to research with disadvantaged groups. Groups of interest were those
      described as socially, culturally or financially disadvantaged compared to the
      majority of society. Eligible articles were categorised according to five phases
      of research: 1) sampling, 2) recruitment and gaining consent, 3) data collection
      and measurement, 4) intervention delivery and uptake, and 5) retention and
      attrition. RESULTS: In total, 116 papers from 115 studies met inclusion criteria
      and 31 previous literature reviews were included. A comprehensive summation of
      the major barriers to working with various disadvantaged groups is provided,
      along with proposed strategies for addressing each of the identified types of
      barriers. Most studies of strategies to address the barriers were of a
      descriptive nature and only nine studies reported the results of randomised
      trials. CONCLUSIONS: To tackle the challenges of research with socially
      disadvantaged groups, and increase their representation in health and medical
      research, researchers and research institutions need to acknowledge extended
      timeframes, plan for higher resourcing costs and operate via community
      partnerships.

PMID- 24669753
TI  - FreeContact: fast and free software for protein contact prediction from residue
      co-evolution.
AB  - BACKGROUND: 20 years of improved technology and growing sequences now renders
      residue-residue contact constraints in large protein families through correlated
      mutations accurate enough to drive de novo predictions of protein three
      dimensional structure. The method EVfold broke new ground using mean-field Direct
      Coupling Analysis (EVfold-mfDCA); the method PSICOV applied a related concept by
      estimating a sparse inverse covariance matrix. Both methods (EVfold-mfDCA and
      PSICOV) are publicly available, but both require too much CPU time for
      interactive applications. On top, EVfold-mfDCA depends on proprietary software.
      RESULTS: Here, we present FreeContact, a fast, open source implementation of
      EVfold-mfDCA and PSICOV. On a test set of 140 proteins, FreeContact was almost
      eight times faster than PSICOV without decreasing prediction performance. The
      EVfold-mfDCA implementation of FreeContact was over 220 times faster than PSICOV
      with negligible performance decrease. EVfold-mfDCA was unavailable for testing
      due to its dependency on proprietary software. FreeContact is implemented as the
      free C++ library "libfreecontact", complete with command line tool "freecontact",
      as well as Perl and Python modules. All components are available as Debian
      packages. FreeContact supports the BioXSD format for interoperability.
      CONCLUSIONS: FreeContact provides the opportunity to compute reliable contact
      predictions in any environment (desktop or cloud).

PMID- 24669756
TI  - Advances in targeted delivery of small interfering RNA using simple
      bioconjugates.
AB  - INTRODUCTION: Development of drugs based on RNA interference by small interfering
      RNA (siRNA) has been progressing slowly due to a number of challenges associated
      with the in vivo behavior of siRNA. A central problem is controlling siRNA
      delivery to specific cell types. Here, we review existing literature on one type
      of strategy for solving the issue of cell-specific delivery of siRNA, namely
      delivering the siRNA as part of simple bioconjugate constructs. AREAS COVERED:
      This review presents current experience from strategies aimed at targeting siRNA
      to specific cell types, by associating the siRNA with a targeting moiety, in a
      simple bioconjugate construct. We discuss the use of different types of targeting
      moieties, as well as the different conjugation strategies employed for preparing
      these bioconjugate constructs that deliver the siRNA to target cells. We focus
      especially on the in-built or passive functionalities associated with each
      strategy, in order to identify key elements of successful siRNA delivery
      strategies with potential for further exploration. EXPERT OPINION: By evaluating
      the current literature on this subject, we identify strategies and concepts that
      are suitable for future studies, to enable the development of highly efficient
      simple bioconjugates for targeted siRNA delivery with therapeutic application.

PMID- 24669757
TI  - Pathway from central obesity to childhood asthma. Physical fitness and sedentary
      time are leading factors.
AB  - RATIONALE: Available prospective studies of obesity and asthma have used only
      body mass index (BMI) as an indicator for adiposity; studies using detailed
      obesity measures are lacking, and the role of physical fitness level and
      sedentary time remains unexplored in the link between obesity and asthma.
      OBJECTIVES: To compare various anthropometric measures of obesity in relation to
      childhood asthma, and to further characterize the interrelations among central
      obesity, physical fitness level, sedentary time, and asthma. METHODS: The
      nationwide Taiwan Children Health Study followed 2,758 schoolchildren from fourth
      to sixth grade, annually collecting data regarding physical fitness, sedentary
      time, obesity measures (comprising body weight and height, abdominal and hip
      circumference, skin fold thickness, and body composition), asthma, and pulmonary
      function tests. The generalized estimating equation was used for 3 years of
      repeated measurements to analyze the interrelation among obesity, sedentary time,
      physical fitness level, and asthma; a structural equation model was used to
      explore the pathogenesis among these factors. Asthma incidence was analyzed
      during a 2-year follow-up among centrally obese and nonobese groups in baseline
      children without asthma. MEASUREMENTS AND MAIN RESULTS: Central obesity most
      accurately predicts asthma. Low physical fitness levels and high screen time
      increase the risk of central obesity, which leads to asthma development. Obesity
      related reduction in pulmonary function is a possible mechanism in the pathway
      from central obesity to asthma. CONCLUSIONS: Central obesity measures should be
      incorporated in childhood asthma risk predictions. Children are encouraged to
      increase their physical fitness levels and reduce their sedentary time to prevent
      central obesity-related asthma.

PMID- 24669758
TI  - Characteristics and motivations of absconders from forensic mental health
      services: a case-control study.
AB  - BACKGROUND: Absconding from hospital is a significant health and security issue
      within psychiatric facilities that can have considerable adverse effects on
      patients, their family members and care providers, as well as the wider
      community. Several studies have documented correlates associated with absconding
      events among general psychiatric samples; however, few studies have examined this
      phenomenon within samples of forensic patients where the perception of threat to
      public safety in the event of an unauthorized absence from hospital is often
      higher. METHODS: We investigate the frequency, timing, and determinants of
      absconding events among a sample of forensic psychiatric patients over a 24-month
      period, and compare patients who abscond to a control group matched along several
      sociodemographic and clinical dimensions. We explore, in a qualitative manner,
      patients' motives for absconding. RESULTS: Fifty-seven patients were responsible
      for 102 incidents of absconding during the two year study window. Forensic
      patients who absconded from hospital were more likely to have a history of
      absconding attempts, a diagnosed substance use disorder, as well as score higher
      on a structured professional violence risk assessment measure. Only one of the
      absconding events identified included an incident of minor violence, and very few
      included the commission of other illegal behaviors (with the exception of
      substance use). The most common reported motive for absconding was a sense of
      boredom or frustration. CONCLUSIONS: Using an inclusive definition of absconding,
      we found that absconding events were generally of brief duration, and that no
      member of the public was harmed by patients who absconded. Findings surrounding
      the motivations of absconders suggest that improvements in therapeutic
      communication between patients and clinical teams could help to reduce the
      occurrence of absconding events.

PMID- 24669760
TI  - In(III) triflate-mediated solvent-free synthesis and activation of thioglycosides
      by ball milling and structural analysis of long chain alkyl thioglycosides by TEM
      and quantum chemical methods.
AB  - Conventional solution-phase synthesis of thioglycosides from glycosyl acetates
      and thiols in the presence of In(III) triflate as reported for benzyl
      thioglucoside failed when applied to the synthesis of phenolic and alkyl
      thioglycosides. But, it was achieved in high efficiency and diastereospecificity
      with ease by solvent-free grinding in a ball mill. The acetates in turn were also
      obtained by the homogenization of free sugars with stoichiometric amounts of
      acetic anhydride and catalytic In(OTf)3 in the mill as neat products. Per-O
      benzylated thioglycosides on grinding with an acceptor sugar in the presence of
      In(OTf)3 yield the corresponding O-glycosides efficiently. The latter in the case
      of a difficult secondary alcohol was nearly exclusive (>98%) in 1,2-cis
      selectivity. In contrast, the conventional methods for this purpose require use
      of a coreagent such as NIS along with the Lewis acid to help generate the
      electrophilic species that actually is responsible for the activation of the
      thioglycoside donor in situ. The distinctly different self-assembling features of
      the peracetylated octadecyl 1-thio-alpha- and beta-D-galactopyranosides observed
      by TEM could be rationalized by molecular modeling.

PMID- 24669759
TI  - Decreased cardiac excitability secondary to reduction of sodium current may be a
      significant contributor to reduced contractility in a rat model of sepsis.
AB  - INTRODUCTION: Multisystem organ failure remains a poorly understood complication
      of sepsis. During sepsis, reduced excitability contributes to organ failure of
      skeletal muscle, nerves and the spinal cord. The goal of this study was to
      determine whether reduced excitability might also contribute to cardiac failure
      during sepsis. METHODS: Wistar rats were made septic by cecal ligation and
      puncture. One day later, action potentials were recorded from beating left
      ventricular papillary muscle ex vivo by impaling myocytes with sharp
      microelectrodes. RESULTS: In cardiac papillary muscle from septic rats, action
      potential amplitude and rate of rise were reduced, while threshold was elevated.
      These changes in action potential properties suggest sepsis selectively reduces
      sodium current. To determine the effects of selective reduction in sodium
      current, we applied tetrodotoxin to papillary muscle from healthy rats and found
      reduction in action potential amplitude and rate of rise, as well as elevation of
      threshold. The changes were similar to those triggered by sepsis. Blocking
      calcium current using nifedipine did not mimic action potential changes induced
      by sepsis. Contractility of healthy papillary muscle was reduced to 40% of normal
      following partial block of sodium current by tetrodotoxin, close to the low
      contractility of septic papillary muscle, which was 30% of normal. CONCLUSIONS:
      Our data suggest cardiac excitability is reduced during sepsis in rats. The
      reduction in excitability appears to be primarily due to reduction of sodium
      current. The reduction in sodium current may be sufficient to explain most of the
      reduction in cardiac contractility during sepsis.

PMID- 24669762
TI  - Photophysics of singlet and triplet intraligand excited states in [ReCl(CO)3(1-(2
      pyridyl)-imidazo[1,5-alpha]pyridine)] complexes.
AB  - Excited-state characters and dynamics of [ReCl(CO)3(3-R-1-(2-pyridyl)-imidazo[1,5
      alpha]pyridine)] complexes (abbreviated ReGV-R, R = CH3, Ph, PhBu(t), PhCF3,
      PhNO2, PhNMe2) were investigated by pico- and nanosecond time-resolved infrared
      spectroscopy (TRIR) and excited-state DFT and TD-DFT calculations. Near UV
      excitation populates the lowest singlet state S1 that undergoes picosecond
      intersystem crossing (ISC) to the lowest triplet T1. Both states are initially
      formed hot and relax with ~20 ps lifetime. TRIR together with quantum chemical
      calculations reveal that S1 is predominantly a pipi* state localized at the 1-(2
      pyridyl)-imidazo[1,5-alpha]pyridine (= impy) ligand core, with impy -> PhNO2 and
      PhNMe2 -> impy intraligand charge-transfer contributions in the case of ReGV
      PhNO2 and ReGV-PhNMe2, respectively. T1 is predominantly pipi*(impy) in all
      cases. It follows that excited singlet and corresponding triplet states have to
      some extent different characters and structures even if originating nominally
      from the same preponderant one-electron excitations. ISC occurs with a solvent
      independent (CH2Cl2, MeCN) 20-30 ps lifetime, except for ReGV-PhNMe2 (10 ps in
      CH2Cl2, 100 ps in MeCN). ISC is 200-300 times slower than in analogous complexes
      with low-lying MLCT states. This difference is interpreted in terms of spin-orbit
      interaction and characters of orbitals involved in one-electron excitations that
      give rise to S1 and T1 states. ReGV-R present a unique case of octahedral heavy
      metal complexes where the S1 lifetime is long enough to allow for separate
      spectroscopic characterization of singlet and triplet excited states. This study
      provides an insight into dynamics and intersystem crossing pathways of low-lying
      singlet and triplet excited states localized at bidentate ligands bound directly
      to a heavy metal atom. Rather long (1)IL lifetimes indicate the possibility of
      photonic applications of singlet excited states. 

PMID- 24669761
TI  - Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute
      myeloid leukemia transformation of chronic myelomonocytic leukemia.
AB  - The FIP1L1-PDGFRA rearrangement results in constitutive activation of the
      tyrosine kinase PDGFRA. Neoplasms harboring this rearrangement are responsive to
      imatinib mesylate at doses much lower than those recommended for the treatment of
      chronic myelogenous leukemia. Only a single report has described the
      identification of FIP1L1-PDGFRA in chronic myelomonocytic leukemia (CMML).
      Herein, we present a case report of a patient in whom the FIP1L1-PDGFRA was
      discovered as he evolved from CMML to acute myeloid leukemia (AML). The presence
      of a dominant neoplastic clone with FIP1L1-PDGFRA rearrangement was suspected on
      the basis of sudden onset of peripheral and bone marrow eosinophilia and
      confirmed by fluorescence in situ hybridization and molecular diagnostic tests.
      Whereas the patient was initially refractory to chemotherapy before the
      rearrangement was detected, subsequent therapy with imatinib led to complete
      remission. 

PMID- 24669764
TI  - Polyphenolic compounds appear to limit the nutritional benefit of biofortified
      higher iron black bean (Phaseolus vulgaris L.).
AB  - BACKGROUND: Our objective was to determine if a biofortified variety of black
      bean can provide more bioavailable-iron (Fe) than a standard variety. Two lines
      of black beans (Phaseolus-vulgaris L.), a standard (DOR500; 59MUg Fe/g) and
      biofortified (MIB465; 88MUg Fe/g) were used. The DOR500 is a common commercial
      variety, and the MIB465 is a line developed for higher-Fe content. Given the high
      prevalence of Fe-deficiency anemia worldwide, it is important to determine if Fe
      biofortified black beans can provide more absorbable-Fe. METHODS: Black bean
      based diets were formulated to meet the nutrient requirements for the broiler
      (Gallus-gallus) except for Fe (dietary Fe-concentrations were 39.4+/-0.2 and
      52.9+/-0.9 mg/kg diet, standard vs. biofortified, respectively). Birds (n=14)
      were fed the diets for 6-weeks. Hemoglobin-(Hb), liver-ferritin and Fe-related
      transporter/enzyme gene-expression were measured. Hemoglobin-maintenance
      efficiency and total-body-Hb-Fe values were used to estimate Fe-bioavailability.
      RESULTS: Hemoglobin-maintenance-efficiency values were higher (P<0.05) in the
      group consuming the standard-Fe beans on days 14, 21 and 28; indicating a
      compensatory response to lower dietary-Fe. Final total-Hb-Fe body content was
      higher in the biofortified vs. the standard group (26.6+/-0.9 and 24.4+/-0.8 mg,
      respectively; P<0.05). There were no differences in liver-ferritin or in
      expression of DMT-1, Dcyt-B, and ferroportin. In-vitro Fe-bioavailability
      assessment indicated very low Fe-bioavailability from both diets and between the
      two bean varieties (P>0.05). Such extremely-low in-vitro Fe-bioavailability
      measurement is indicative of the presence of high levels of polyphenolic
      compounds that may inhibit Fe-absorption. High levels of these compounds would be
      expected in the black bean seed-coats. CONCLUSIONS: The parameters of Fe-status
      measured in this study indicate that only a minor increase in absorbable-Fe was
      achieved with the higher-Fe beans. The results also raise the possibility that
      breeding for increased Fe-concentration elevated the levels of polyphenolic
      compounds that can reduce bean Fe-bioavailability, although the higher levels of
      polyphenolics in the higher-Fe beans may simply be coincidental or an
      environmental effect. Regardless, Fe-biofortified beans remain a promising
      vehicle for increasing intakes of bioavailable-Fe in human populations that
      consume high levels of these beans as a dietary staple, and the bean polyphenol
      profile must be further evaluated and modified if possible in order to improve
      the nutritional quality of higher-Fe beans.

PMID- 24669763
TI  - Functional annotation of proteome encoded by human chromosome 22.
AB  - As part of the chromosome-centric human proteome project (C-HPP) initiative, we
      report our progress on the annotation of chromosome 22. Chromosome 22, spanning
      51 million base pairs, was the first chromosome to be sequenced. Gene dosage
      alterations on this chromosome have been shown to be associated with a number of
      congenital anomalies. In addition, several rare but aggressive tumors have been
      associated with this chromosome. A number of important gene families including
      immunoglobulin lambda locus, Crystallin beta family, and APOBEC gene family are
      located on this chromosome. On the basis of proteomic profiling of 30
      histologically normal tissues and cells using high-resolution mass spectrometry,
      we show protein evidence of 367 genes on chromosome 22. Importantly, this
      includes 47 proteins, which are currently annotated as "missing" proteins. We
      also confirmed the translation start sites of 120 chromosome 22-encoded proteins.
      Employing a comprehensive proteogenomics analysis pipeline, we provide evidence
      of novel coding regions on this chromosome which include upstream ORFs and novel
      exons in addition to correcting existing gene structures. We describe tissue-wise
      expression of the proteins and the distribution of gene families on this
      chromosome. These data have been deposited to ProteomeXchange with the identifier
      PXD000561. 

PMID- 24669766
TI  - Application of artificial palpation in vascular surgeries for detection of
      peripheral arterial stenosis.
AB  - Palpation is one of the applied methods that surgeons usually use during surgery
      in order to verify the health condition of a tissue/organ. In fact, most of
      surgical assessments are based on analysis of the force feedback received from
      tissue/organ via palpation. Although palpation has a key role in efficient
      progress of surgery operations, it depends very much on the experience and skill
      of the surgeons. This limits the application of this technique in some cases to a
      large extent. In this regard, an artificial tactile sensing approach is an
      innovative technology that tries to make tactile data more available for
      surgeons, especially in situations where doing the palpation is not possible or
      is too difficult. In this paper, having considered the present problems of artery
      bypass surgery in peripheral arterial occlusive disease (PAOD), applicability of
      a new tactile sensory system capable of detecting arterial stenosis during
      surgery was evaluated. Presenting the modelling and numerical solution of the
      problem, it was demonstrated that the artificial tactile sensing approach is not
      only capable of detecting the presence of an arterial stenosis in an artery, but
      also its type. Furthermore, it was shown that the new tactile sensory system
      (previously designed, fabricated and tested in laboratory) is efficiently capable
      of detecting the simulated artery in the simulated biological tissue as well as
      diagnosis of the stenosis occurred inside it.

PMID- 24669765
TI  - Expert Recommendations for Implementing Change (ERIC): protocol for a mixed
      methods study.
AB  - BACKGROUND: Identifying feasible and effective implementation strategies that are
      contextually appropriate is a challenge for researchers and implementers,
      exacerbated by the lack of conceptual clarity surrounding terms and definitions
      for implementation strategies, as well as a literature that provides imperfect
      guidance regarding how one might select strategies for a given healthcare quality
      improvement effort. In this study, we will engage an Expert Panel comprising
      implementation scientists and mental health clinical managers to: establish
      consensus on a common nomenclature for implementation strategy terms, definitions
      and categories; and develop recommendations to enhance the match between
      implementation strategies selected to facilitate the use of evidence-based
      programs and the context of certain service settings, in this case the U.S.
      Department of Veterans Affairs (VA) mental health services. METHODS/DESIGN: This
      study will use purposive sampling to recruit an Expert Panel comprising
      implementation science experts and VA mental health clinical managers. A novel,
      four-stage sequential mixed methods design will be employed. During Stage 1, the
      Expert Panel will participate in a modified Delphi process in which a published
      taxonomy of implementation strategies will be used to establish consensus on
      terms and definitions for implementation strategies. In Stage 2, the panelists
      will complete a concept mapping task, which will yield conceptually distinct
      categories of implementation strategies as well as ratings of the feasibility and
      effectiveness of each strategy. Utilizing the common nomenclature developed in
      Stages 1 and 2, panelists will complete an innovative menu-based choice task in
      Stage 3 that involves matching implementation strategies to hypothetical
      implementation scenarios with varying contexts. This allows for quantitative
      characterizations of the relative necessity of each implementation strategy for a
      given scenario. In Stage 4, a live web-based facilitated expert recommendation
      process will be employed to establish expert recommendations about which
      implementations strategies are essential for each phase of implementation in each
      scenario. DISCUSSION: Using a novel method of selecting implementation strategies
      for use within specific contexts, this study contributes to our understanding of
      implementation science and practice by sharpening conceptual distinctions among a
      comprehensive collection of implementation strategies.

PMID- 24669767
TI  - Helping women to good health: breast cancer, omega-3/omega-6 lipids, and related
      lifestyle factors.
AB  - In addition to genetic predisposition and sex hormone exposure, physical activity
      and a healthy diet play important roles in breast cancer (BC). Increased intake
      of omega-3 fatty acids (n-3) associated with decreased omega-6 (n-6), resulting
      in a higher n-3/n-6 ratio compared with the western diet, are inversely
      associated with BC risk, as shown by Yang et al. in their meta-analysis in BMC
      Cancer. High consumption of polyphenols and organic foods increase the n-3/n-6
      ratio, and in turn may decrease BC risk. Intake of high fiber foods and foods
      with low glycemic index decreases insulin resistance and diabetes risk, and in
      turn may decrease BC risk. The modernized Mediterranean diet is an effective
      strategy for combining these recommendations, and this dietary pattern reduces
      overall cancer risk and specifically BC risk. High-risk women should also
      eliminate environmental endocrine disruptors, including those from foods. Drugs
      that decrease the n-3/n-6 ratio or that are suspected of increasing BC or
      diabetes risk should be used with great caution by high-risk women and women
      wishing to decrease their BC risk.Please see related article:
      http://www.biomedcentral.com/1471-2407/14/105/abstract. 

PMID- 24669768
TI  - Therapeutic potential of apigenin, a plant flavonoid, for imatinib-sensitive and
      resistant chronic myeloid leukemia cells.
AB  - Despite the presence of many therapeutic regimens like imatinib and other
      tyrosine kinase inhibitors, the development of resistance, intolerance, and side
      effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is
      a need to discover novel drugs for CML patients. In this study, we attempted to
      assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic,
      apoptotic, and cytostatic effects on imatinib-sensitive and resistant
      Philadelphia-positive CML cells. We analyzed apigenin's effects on cell
      proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane
      potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore,
      we described genes and gene networks that are modulated in CML in response to
      apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic
      effects on both cell types. We also displayed that apigenin induced G2/M arrest
      in K562 cells while arresting K562/IMA3 cells in S phase especially at the
      highest apigenin concentration. The expression analysis identified a set of genes
      that were regulated by apigenin in K652 and K562/IMA3 cells. Association of
      modulated genes with biological functional groups identified several networks
      affected by apigenin including cell survival, proliferation, cell death, cell
      cycle, and cell signalling pathways. 

PMID- 24669769
TI  - A graph theoretic approach to utilizing protein structure to identify non-random
      somatic mutations.
AB  - BACKGROUND: It is well known that the development of cancer is caused by the
      accumulation of somatic mutations within the genome. For oncogenes specifically,
      current research suggests that there is a small set of "driver" mutations that
      are primarily responsible for tumorigenesis. Further, due to recent
      pharmacological successes in treating these driver mutations and their resulting
      tumors, a variety of approaches have been developed to identify potential driver
      mutations using methods such as machine learning and mutational clustering. We
      propose a novel methodology that increases our power to identify mutational
      clusters by taking into account protein tertiary structure via a graph
      theoretical approach. RESULTS: We have designed and implemented GraphPAC (Graph
      Protein Amino acid Clustering) to identify mutational clustering while
      considering protein spatial structure. Using GraphPAC, we are able to detect
      novel clusters in proteins that are known to exhibit mutation clustering as well
      as identify clusters in proteins without evidence of prior clustering based on
      current methods. Specifically, by utilizing the spatial information available in
      the Protein Data Bank (PDB) along with the mutational data in the Catalogue of
      Somatic Mutations in Cancer (COSMIC), GraphPAC identifies new mutational clusters
      in well known oncogenes such as EGFR and KRAS. Further, by utilizing graph theory
      to account for the tertiary structure, GraphPAC discovers clusters in DPP4, NRP1
      and other proteins not identified by existing methods. The R package is available
      at: http://bioconductor.org/packages/release/bioc/html/GraphPAC.html. CONCLUSION:
      GraphPAC provides an alternative to iPAC and an extension to current methodology
      when identifying potential activating driver mutations by utilizing a graph
      theoretic approach when considering protein tertiary structure.

PMID- 24669772
TI  - Understanding water permeation in graphene oxide membranes.
AB  - Water transport through graphene-derived membranes has gained much interest
      recently due to its promising potential in filtration and separation
      applications. In this work, we explore water permeation in graphene oxide
      membranes using atomistic simulations and theoretical analysis, by considering
      flow through the interlayer gallery, expanded channels such as wrinkles of
      interedge spaces, and pores within the sheet. We find that, although flow
      enhancement can be established by nanoconfinement, fast water transport through
      pristine graphene channels is prohibited by a prominent side-pinning effect from
      capillaries formed within oxidized regions. We then discuss several flow
      enhancement mechanisms through the porous microstructures of graphene oxide
      membranes. These understandings are integrated into a complete picture to
      understand water permeation through the layer-by-layer and porous microstructure
      and can guide rational design of functional membranes for energy and
      environmental applications. 

PMID- 24669770
TI  - Child sexual abuse in religiously affiliated and secular institutions: a
      retrospective descriptive analysis of data provided by victims in a government
      sponsored reappraisal program in Germany.
AB  - BACKGROUND: The disclosure of widespread sexual abuse committed by professional
      educators and clergymen in institutions in Germany ignited a national political
      debate, in which special attention was paid to church-run institutions. We wanted
      to find out whether the nature of the abuse and its effect on victims differed
      depending on whether the abuse had been experienced in religiously affiliated
      versus secular institutions. METHODS: In 2010, the German government established
      a hotline that victims could contact anonymously to describe their experiences of
      sexual abuse. The information provided by callers was documented and categorized.
      Our analysis looked at a subset of the data collected, in order to compare the
      nature of the abuse experienced at three types of institutions: Roman Catholic,
      Protestant, and non-religiously affiliated. Non-parametric tests were used to
      compare frequency distributions, and qualitative data were analyzed
      descriptively. RESULTS: Of the 1050 victims in our sample, 404 had been in Roman
      Catholic, 130 in Protestant, and 516 in non-religious institutions. The overall
      mean age at the time of reporting was 52.2 years. Males (59.8%) outnumbered
      females. Victims who had been in religiously affiliated institutions were
      significantly older than those who had been in secular institutions. Almost half
      the victims had been abused physically as well as sexually, and most victims
      reported that the abuse had occurred repeatedly and that the assaults had been
      committed by males. Patterns of abuse (time, type, and extent), and the gender of
      the offenders did not differ between the three groups. Intercourse was more
      frequently reported by older victims and by females. Similar percentages of
      victims in all groups reported current psychiatric diagnoses (depression, anxiety
      disorders, PTSD). Significantly more victims from Protestant institutions
      reported having current psychosocial problems. CONCLUSION: The results suggest
      that child sexual abuse in institutions is attributable to the nature of
      institutional structures and to societal assumptions about the rights of children
      more than to the attitudes towards sexuality of a specific religion. The
      exploratory data arising from this study may serve as a starting point for
      building hypotheses, and may point the way toward improvements in prevention and
      intervention strategies.

PMID- 24669771
TI  - Allocating operating room resources to an acute care surgery service does not
      affect wait-times for elective cancer surgeries: a retrospective cohort study.
AB  - INTRODUCTION: Acute care surgical services provide timely comprehensive emergency
      general surgical care while optimizing the use of limited resources. At our
      institution, 50% of the daily dedicated operating room (OR) time allocated to the
      Acute Care Emergency Surgery Service (ACCESS) came from previous elective general
      surgery OR time. We assessed the impact of this change in resource allocation on
      wait-times for elective general surgery cancer cases. METHODS: We retrospectively
      reviewed adult patients who underwent elective cancer surgeries in the pre-ACCESS
      (September 2009 to June 2010) and post-ACCESS (September 2010 to June 2011) eras.
      Wait-times, calculated as the time between booking and actual dates of surgery,
      were compared within assigned priority classifications. Categorical and
      continuous variables were compared using chi-square and Mann-Whitney U tests
      respectively. RESULTS: A total of 732 cases (367 pre-ACCESS and 365 post-ACCESS)
      were identified, with no difference in median wait-times (25 versus 23 days)
      between the eras. However, significantly fewer cases exceeded wait-time targets
      in the post-ACCESS era (p <0.0001). There was a significant change (p = 0.027) in
      the composition of cancer cases, with fewer breast cancer operations (22% versus
      28%), and more colorectal (41% versus 32%) and hepatobiliary cancer cases (5%
      versus 2%) in the post-ACCESS era. CONCLUSION: These results suggest that
      shifting OR resources towards emergency surgery does not affect the timeliness of
      surgical cancer care. This study may encourage more centres to adopt acute care
      surgical services alongside their elective or subspecialty practices.

PMID- 24669773
TI  - Cancer survival in Lithuania after the restoration of independence: rapid
      improvements, but persisting major gaps.
AB  - BACKGROUND: Following restoration of political independence in 1990, Lithuania
      underwent rapid societal and economic changes. We aimed to assess trends in
      cancer survival in the first two decades following these changes. MATERIAL AND
      METHODS: We used population-based data from the Lithuanian Cancer Registry and
      period analysis techniques to examine trends in one-, 2-5- and five-year relative
      survival between 1995-1999 and 2005-2009 for 24 common cancers in Lithuania.
      RESULTS: Between 1995-1999 and 2005-2009, five-year relative survival increased
      significantly for 20 of 24 cancers, and for 10 cancers the increase exceeded 10%
      units. Five-year relative survival estimates reached 46%, 69% and 91% for
      colorectal, breast and prostate cancer in 2005-2009, respectively, while patients
      with testicular cancer, Hodgkin's or non-Hodgkin's lymphoma had a five-year
      relative survival of 77%, 75% and 50%, respectively. CONCLUSION: We found a rapid
      increase in survival for most forms of common cancers in Lithuania between 1995
      and 2009. Nevertheless, several cancers with effective therapies exhibit
      considerable gaps compared with Northern and Western European countries. Despite
      ongoing rises in survival, mortality declines are not yet manifesting for
      important common cancers such as breast and colorectal cancer. Rapid incidence
      rises suggest that increases in survival for prostate and thyroid cancers are
      massively influenced by early detection-related effects. Improving the
      availability of effective therapies, and carefully planned early detection
      programs may help to increase cancer survival in Lithuania in the future.

PMID- 24669774
TI  - Radiation-induced trismus in the ARTSCAN head and neck trial.
AB  - Trismus, a well-known sequelae after treatment of head and neck cancer, decreases
      a patient's oral function and quality of life. The main objectives of this study
      were to: 1) investigate the long-term prevalence of radiation-induced trismus in
      patients treated for head and neck cancer according to two different
      fractionation schedules; and 2) model a dose-response relationship for trismus.
      MATERIAL AND METHODS: Patients were recruited from the Swedish ARTSCAN trial, a
      prospective randomised multicentre study comparing conventional and accelerated
      fractionation. A total of 124 patients agreed to a clinical ENT examination 21
      127 months (median 66 months) after beginning radiation therapy. Trismus-related
      scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The
      TheraBite((r)) range of motion scale was used to measure maximal interincisal
      distance. The dose-response relationship for structures important for mastication
      and the temporomandibular joints was investigated by normal tissue complication
      probability modelling. RESULTS: No significant differences in patient-reported
      trismus or maximal interincisal distance were found between the two trial arms.
      Patient-reported moderate to high scores regarding trismus increased from 3% at
      the start of radiation therapy to 25% at the long-term follow-up. Maximal
      interincisal distance correlated significantly with patient-reported scores of
      trismus. The best dose-response fit to the endpoint data was found for the dose
      to the ipsilateral masseter. CONCLUSIONS: Trismus is a persistent complication
      after radiotherapy with 3D-conformal radiation therapy. We found no difference
      between the severity and prevalence of trismus between conventional and
      accelerated fractionation, but a significant correlation between the absorbed
      dose to the mastication structures and opening of the mouth. Further prospective
      studies may determine whether a reduced dose to structures important for
      mastication using intensity-modulated radiation therapy will reduce problems with
      trismus.

PMID- 24669776
TI  - Comparison of plutonium systemic distribution in rats and dogs with published
      data in humans.
AB  - PURPOSE: This manuscript compares the behavior of monomeric (239)Pu(4+)-citrate
      injected intravenously in rats and dogs with a comparison of available humans'
      data. MATERIAL AND METHODS: The experimental design for these two studies
      consisted of eight groups sacrificed at predetermined time-points post exposure.
      All organs and tissues as well as daily urinary and fecal excretion were
      analyzed. RESULTS: Liver and skeleton were the organs with the highest (239)Pu
      uptake in both species; 76% in dogs and 70% in rats at 24 hours (h) post IV
      administration. By the end of the study (28 days, d), the activity in skeleton
      and liver was 85% in dogs and 65% in rats. The urinary excretion function seems
      to be similar for rats, dogs and humans but the daily fecal to urinary excretion
      ratio differs between species. CONCLUSION: A rapid clearance from the liver of
      rats was observed compared to dogs. Skeleton-to-liver ratios are variable between
      species. Urinary and fecal excretion patterns for dogs are consistent with human
      data, indicating that dogs seem to represent better the (239)Pu behavior in
      humans. The data confirm that the better animal model to evaluate the efficacy of
      (239)Pu chelating compounds is the canine model.

PMID- 24669775
TI  - Mitotic asynchrony induces transforming growth factor-beta1 secretion from airway
      epithelium.
AB  - We recently proposed that mitotic asynchrony in repairing tissue may underlie
      chronic inflammation and fibrosis, where immune cell infiltration is secondary to
      proinflammatory cross-talk among asynchronously repairing adjacent tissues.
      Building on our previous finding that mitotic asynchrony is associated with
      proinflammatory/fibrotic cytokine secretion (e.g., transforming growth factor
      [TGF]-beta1), here we provide evidence supporting cause-and-effect. Under normal
      conditions, primary airway epithelial basal cell populations undergo mitosis
      synchronously and do not secrete proinflammatory or profibrotic cytokines.
      However, when pairs of nonasthmatic cultures were mitotically synchronized at 12
      hours off-set and then combined, the mixed cell populations secreted elevated
      levels of TGF-beta1. This shows that mitotic asynchrony is not only associated
      with but is also causative of TGF-beta1 secretion. The secreted cytokines and
      other mediators from asthmatic cells were not the cause of asynchronous
      regeneration; synchronously mitotic nonasthmatic epithelia exposed to conditioned
      media from asthmatic cells did not show changes in mitotic synchrony. We also
      tested if resynchronization of regenerating asthmatic airway epithelia reduces
      TGF-beta1 secretion and found that pulse-dosed dexamethasone, simvastatin, and
      aphidicolin were all effective. We therefore propose a new model for chronic
      inflammatory and fibrotic conditions where an underlying factor is mitotic
      asynchrony. 

PMID- 24669777
TI  - Poly(ADP-ribose) polymerase activation mediates synchrotron radiation X-ray
      induced damage of rodent testes by exacerbating DNA damage and apoptotic changes.
AB  - PURPOSES: Synchrotron radiation (SR) X-ray has great potential for cancer
      treatment and medical imaging. It is of significance to investigate the
      mechanisms underlying the effects of SR X-ray irradiation on biological tissues,
      and search for the strategies for preventing the damaging effects of SR X-ray
      irradiation on normal tissues. The major aim of our current study is to test our
      hypothesis that poly(ADP-ribose) polymerase (PARP) plays a significant role in SR
      X-ray-induced tissue damage. METHODS AND MATERIALS: The testes of rodents were
      pre-treated with PARP inhibitor 3-aminobenzamide (3-AB) or antioxidant N-acetyl
      acetylcysteine (NAC), followed by SR X-ray irradiation. PARP activation, double
      strand DNA breaks (DSB), Terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) signals, caspase-3 activity and weight of the testes were
      determined. RESULTS: SR X-ray irradiation produced dose-dependent increases in
      poly(ADP-ribose) (PAR) formation - an index of PARP activation, which can be
      prevented by NAC administration. Administration of 10 or 20 mg/kg 3-AB attenuated
      a variety of tissue injury induced by SR X-ray, including caspase-3 activation,
      increases in TUNEL signals and loss of testical weight. The PARP inhibitor also
      significantly decreased SR X-ray-induced gamma-H2AX signal - a marker of DSB.
      CONCLUSIONS: Our study has provided the first evidence suggesting that SR X-ray
      can induce PARP activation by generating oxidative stress, which leads to various
      tissue injuries at least partially by exacerbating DNA damage and apoptotic
      changes.

PMID- 24669778
TI  - Deoxyglucose prevents neurodegeneration in culture by eliminating microglia.
AB  - BACKGROUND: 2-Deoxy-D-glucose is an inhibitor of glycolysis, which is protective
      in animal models of brain pathology, but the mechanisms of this protection are
      unclear. We examined whether, when and how deoxyglucose protects neurons in co
      culture with astrocytes and microglia. Microglia are brain macrophages, which can
      damage neurons in inflammatory conditions. METHODS: Deoxyglucose was added to
      primary cultures of microglia and astrocytes from rat cortex, or neurons and glia
      from rat cerebellum, or the BV-2 microglial cell line, and cell death and cell
      functions were evaluated. RESULTS: Surprisingly, addition of deoxyglucose induced
      microglial loss and prevented spontaneous neuronal loss in long-term cultures of
      neurons and glia, while elimination of microglia by L-leucine-methyl ester
      prevented the deoxyglucose-induced neuroprotection. Deoxyglucose also prevented
      neuronal loss induced by addition of amyloid beta or disrupted neurons (culture
      models of Alzheimer's disease and brain trauma respectively). However,
      deoxyglucose greatly increased the neuronal death induced by hypoxia. Addition of
      deoxyglucose to pure microglia induced necrosis and loss, preceded by rapid ATP
      depletion and followed by phagocytosis of the microglia. Deoxyglucose did not
      kill astrocytes or neurons. CONCLUSIONS: We conclude that deoxyglucose causes
      microglial loss by ATP depletion, and this can protect neurons from
      neurodegeneration, except in conditions of hypoxia. Deoxyglucose may thus be
      beneficial in brain pathologies mediated by microglia, including brain trauma,
      but not where hypoxia is involved.

PMID- 24669779
TI  - Biomaterial-based scaffolds--current status and future directions.
AB  - INTRODUCTION: Biomaterial-based scaffold formulations (three-dimensional Porous
      matrix, nano-fibre mesh, hydrogels and microspheres) are the major components
      that are used to deliver the bioactive molecules into the body organs through
      different routes for an effective treatment of various diseases. AREAS COVERED:
      Various fabrication techniques such as freeze-drying, polymerisation, spray
      drying, gas foaming, supercritical fluid technology, etc., are successfully used
      for fabrication of scaffold formulations. Due to their unique characteristics,
      these formulations are widely used against various diseases such as tuberculosis,
      bone defects, cartilage repair, skin diseases, cardiovascular diseases,
      periodontal diseases, wound dressing, etc. EXPERT OPINION: The study of
      biomaterial-based scaffold formulations is exhilarating with novel approaches to
      drug/cell/gene delivery being developed all the time. At present, there is a huge
      extent of research being performed worldwide on all aspects of tissue
      engineering/drug or gene delivery. In the future, the main focus will be on the
      development of more patient compliant, sustained and controlled delivery systems
      against various diseases by modification of polymers, manufacturing technologies
      as well as carrier systems.

PMID- 24669781
TI  - Electron beam lithography on irregular surfaces using an evaporated resist.
AB  - An electron beam resist is typically applied by spin-coating, which cannot be
      reliably applied on nonplanar, irregular, or fragile substrates. Here we
      demonstrate that the popular negative electron beam resist polystyrene can be
      coated by thermal evaporation. A high resolution of 30 nm half-pitch was achieved
      using the evaporated resist. As a proof of concept of patterning on irregular
      surfaces, we fabricated nanostructures on the AFM cantilever and the optical
      fiber. Although an ice (H2O) resist has also been recently demonstrated as being
      capable of nanopatterning on irregular and fragile substrates, it requires
      specially designed accessories mounted inside a SEM chamber, whereas our process
      works with any thermal evaporator and is thus simpler and much more accessible.
      Nanofabrication on nonplanar surfaces may find applications in fields such as
      (AFM) tip-enhanced Raman spectroscopy for chemical analysis and lab-on-fiber
      technology. 

PMID- 24669780
TI  - Human coronary plaque wall thickness correlated positively with flow shear stress
      and negatively with plaque wall stress: an IVUS-based fluid-structure interaction
      multi-patient study.
AB  - BACKGROUND: Atherosclerotic plaque progression and rupture are believed to be
      associated with mechanical stress conditions. In this paper, patient-specific in
      vivo intravascular ultrasound (IVUS) coronary plaque image data were used to
      construct computational models with fluid-structure interaction (FSI) and cyclic
      bending to investigate correlations between plaque wall thickness and both flow
      shear stress and plaque wall stress conditions. METHODS: IVUS data were acquired
      from 10 patients after voluntary informed consent. The X-ray angiogram was
      obtained prior to the pullback of the IVUS catheter to determine the location of
      the coronary artery stenosis, vessel curvature and cardiac motion. Cyclic bending
      was specified in the model representing the effect by heart contraction. 3D
      anisotropic FSI models were constructed and solved to obtain flow shear stress
      (FSS) and plaque wall stress (PWS) values. FSS and PWS values were obtained for
      statistical analysis. Correlations with p < 0.05 were deemed significant.
      RESULTS: Nine out of the 10 patients showed positive correlation between wall
      thickness and flow shear stress. The mean Pearson correlation r-value was 0.278
      +/- 0.181. Similarly, 9 out of the 10 patients showed negative correlation
      between wall thickness and plaque wall stress. The mean Pearson correlation r
      value was -0.530 +/- 0.210. CONCLUSION: Our results showed that plaque vessel
      wall thickness correlated positively with FSS and negatively with PWS. The
      patient-specific IVUS-based modeling approach has the potential to be used to
      investigate and identify possible mechanisms governing plaque progression and
      rupture and assist in diagnosis and intervention procedures. This represents a
      new direction of research. Further investigations using more patient follow-up
      data are warranted.

PMID- 24669782
TI  - Proteasomal serine hydrolases are up-regulated by and required for influenza
      virus infection.
AB  - Interactions between viruses and their host cells are important determinants of
      virus replication and of immune responses to the virus. However, these
      interactions and resulting consequences of these interactions remain poorly
      defined. Numerous recent quantitative proteomic approaches have measured host
      proteins affected by virus infection. Here, we used activity-based protein
      profiling (ABPP) to measure functional alterations in host serine hydrolases
      after influenza A virus infection of Madin-Darby canine kidney and human A549
      lung cells. We identified 62 serine proteases. We then combined the ABPP approach
      with stable isotope labeling to directly measure how serine hydrolase activities
      were affected by virus infection. Differentially regulated SHs mapped into a few
      key cellular pathway systems, most notably the proteasomal system. The specific
      serine protease inhibitors Aprotinin and Pefablock and specific proteasomal
      inhibitors Bortezomib and MG132 significantly inhibited influenza virus growth.
      Some inhibitors also down-regulated activities of several proteasomal proteins,
      including PSMA1, PSMA2, and PMSB3. Genetic knockdown of PMSA2 also attenuated
      influenza virus replication. These findings further our understanding of
      enzymatic cellular processes affected by influenza virus and may be beneficial in
      the search for additional antiviral therapeutic targets. 

PMID- 24669783
TI  - Risk factors of rotavirus diarrhea in hospitalized children in Sanglah Hospital,
      Denpasar: a prospective cohort study.
AB  - BACKGROUND: Diarrhea is a major public health concern throughout the world
      because the prevalence of morbidity of diarrhea has not changed significantly in
      the past decade. It remains the third leading cause of death among children less
      than 5 years of age. Recent surveillance studies have shown that rotavirus is a
      significant cause of pediatric hospitalization and death due to diarrhea.
      Indonesia has limited data on risk factors, disease burden, and deaths in
      children due to rotavirus diarrhea. The objective of this study was to examine
      the above mentioned factors related to rotavirus diarrhea in hospitalized
      children in Sanglah Hospital, Denpasar. METHODS: A prospective cohort study was
      conducted at Sanglah Hospital Denpasar from April 2009 to December 2011. The
      present study was part of a nationwide study on Extension for Hospital-based
      Surveillance and Strain Characterization of Rotavirus Diarrhea Indonesia
      involving four hospitals throughout Indonesia as a part of the Asian Rotavirus
      Surveillance Network. We studied children aged <5 years who were hospitalized
      with acute diarrhea, and analyzed their stool samples using an immunoassay that
      detects the rotavirus antigen. RESULTS: A total of 656 patients met the inclusion
      criteria for this study. Of 5805 patients under the age of 5 who were
      hospitalized between April 2009 and December 2011, the prevalence of diarrhea
      among hospitalized pediatric patients was 11.3% and the prevalence of rotavirus
      diarrhea was 49.8%. The male to female ratio of those affected by rotavirus was
      1.6:1. The occurrence of vomiting was significantly higher in rotavirus diarrhea
      than in non-rotavirus diarrhea (RR, 1.4; 95% CI, 1.08 to 1.70; p = 0.004).
      CONCLUSIONS: Diarrhea remains an important cause of hospitalization in children,
      and rotavirus was the most important etiology. We found that boys had a greatest
      risk of rotavirus infection than girls. Good nutritional status and breastfeeding
      provided the same protection against rotavirus and non-rotavirus diarrhea.

PMID- 24669784
TI  - Construct validity of the Chelsea critical care physical assessment tool: an
      observational study of recovery from critical illness.
AB  - INTRODUCTION: Intensive care unit-acquired weakness (ICU-AW) is common in
      survivors of critical illness, resulting in global weakness and functional
      deficit. Although ICU-AW is well described subjectively in the literature, the
      value of objective measures has yet to be established. This project aimed to
      evaluate the construct validity of the Chelsea Critical Care Physical Assessment
      tool (CPAx) by analyzing the association between CPAx scores and hospital
      discharge location, as a measure of functional outcome. METHODS: The CPAx was
      integrated into practice as a service-improvement initiative in an 11-bed
      intensive care unit (ICU). For patients admitted for more than 48 hours, between
      10 May 2010 and 13 November 2013, the last CPAx score within 24 hours of step
      down from the ICU or death was recorded (n = 499). At hospital discharge,
      patients were separated into seven categories, based on continued rehabilitation
      and care needs. Descriptive statistics were used to explore the association
      between ICU discharge CPAx score and hospital-discharge location. RESULTS: Of the
      499 patients, 171 (34.3%) returned home with no ongoing rehabilitation or care
      input; 131 (26.2%) required community support; 28 (5.6%) went to inpatient
      rehabilitation for <6 weeks; and 25 (5.0%) went to inpatient rehabilitation for
      >6 weeks; 27 (5.4%) required nursing home level of care; 80 (16.0%) died in the
      ICU, and 37 (7.4%) died in hospital. A significant difference was found in the
      median CPAx score between groups (P < 0.0001). Four patients (0.8%) scored full
      marks (50) on the CPAx, all of whom went home with no ongoing needs; 16 patients
      (3.2%) scored 0 on the CPAx, all of whom died within 24 hours. A 0.8% ceiling
      effect and a 3.2% floor effect of the CPAx is found in the ICU. Compliance with
      completion of the CPAx stabilized at 78% of all ICU admissions. CONCLUSION: The
      CPAx score at ICU discharge has displayed construct validity by crudely
      discriminating between groups with different functional needs at hospital
      discharge. The CPAx has a limited floor and ceiling effect in survivors of
      critical illness. A significant proportion of patients had a requirement for
      postdischarge care and rehabilitation.

PMID- 24669785
TI  - Polymorphism of oligomers of a peptide from beta-amyloid.
AB  - This contribution reports solution-phase structural studies of oligomers of a
      family of peptides derived from the beta-amyloid peptide (Abeta). We had
      previously reported the X-ray crystallographic structures of the oligomers and
      oligomer assemblies formed in the solid state by a macrocyclic beta-sheet peptide
      containing the Abeta(15-23) nonapeptide. In the current study, we set out to
      determine its assembly in aqueous solution. In the solid state, macrocyclic beta
      sheet peptide 1 assembles to form hydrogen-bonded dimers that further assemble in
      a sandwich-like fashion to form tetramers through hydrophobic interactions
      between the faces bearing V18 and F20. In aqueous solution, macrocyclic beta
      sheet peptide 1 and homologue 2a form hydrogen-bonded dimers that assemble to
      form tetramers through hydrophobic interactions between the faces bearing L17,
      F19, and A21. In the solid state, the hydrogen-bonded dimers are antiparallel,
      and the beta-strands are fully aligned, with residues 17-23 of one of the
      macrocycles aligned with residues 23-17 of the other. In solution, residues 17-23
      of the hydrogen-bonded dimers are shifted out of alignment by two residues toward
      the C-termini. The two hydrogen-bonded dimers are nearly orthogonal in the solid
      state, while in solution the dimers are only slightly rotated. The differing
      morphology of the solution-state and solid-state tetramers is significant,
      because it may provide a glimpse into some of the structural bases for
      polymorphism among Abeta oligomers in Alzheimer's disease.

PMID- 24669786
TI  - Liver fat accumulation is associated with reduced hepatic insulin extraction and
      beta cell dysfunction in healthy older individuals.
AB  - BACKGROUND: There is a well-established association between type 2 diabetes and
      non-alcoholic fatty liver disease (NAFLD) secondary to excess accumulation of
      intrahepatic lipid (IHL), but the mechanistic basis for this association is
      unclear. Emerging evidence suggests that in addition to being associated with
      insulin resistance, NAFLD may be associated with relative beta-cell dysfunction.
      We sought to determine the influence of liver fat on hepatic insulin extraction
      and indices of beta-cell function in a cohort of apparently healthy older white
      adults. METHODS: We performed a cross-sectional analysis of 70 healthy
      participants in the Hertfordshire Physical Activity Trial (39 males, age 71.3 +/-
      2.4 years) who underwent oral glucose tolerance testing with glucose, insulin and
      C-Peptide levels measured every 30 minutes over two hours. The areas under the
      concentration curve for glucose, insulin and C-Peptide were used to quantify
      hepatic insulin extraction (HIE), the insulinogenic index (IGI), the C-Peptide
      increment (CGI), the Disposition Index (DI) and Adaptation Index (AI). Visceral
      fat was quantified with magnetic resonance (MR) imaging and IHL with MR
      spectroscopy. Insulin sensitivity was measured with the Oral Glucose Insulin
      Sensitivity (OGIS) model. RESULTS: 29 of 70 participants (41%) exceeded our
      arbitrary threshold for NAFLD, i.e. IHL >5.5%. Compared to those with normal IHL,
      those with NAFLD had higher weight, BMI, waist and MR visceral fat, with lower
      insulin sensitivity and hepatic insulin extraction. Alcohol consumption, age,
      HbA1c and alanine aminotransferase (ALT) levels were similar in both groups.
      Insulin and C-Peptide excursions after oral glucose loading were higher in the
      NAFLD group, but the CGI and AI were significantly lower, indicating a relative
      defect in beta-cell function that is only apparent when C-Peptide is measured and
      when dynamic changes in glucose levels and also insulin sensitivity are taken
      into account. There was no difference in IGI or DI between the groups.
      CONCLUSIONS: Although increased IHL was associated with greater insulin
      secretion, modelled parameters suggested relative beta-cell dysfunction with
      NAFLD in apparently healthy older adults, which may be obscured by reduced
      hepatic insulin extraction. Further studies quantifying pancreatic fat content
      directly and its influence on beta cell function are warranted. TRIAL
      REGISTRATION: ISRCTN60986572.

PMID- 24669787
TI  - Perceived variety, psychological needs satisfaction and exercise-related well
      being.
AB  - OBJECTIVE: Perceived variety represents a psychosocial experience that gives rise
      to, and supports the maintenance of, an individual's well-being. In this study,
      we developed an instrument to measure perceived variety in exercise (PVE), and
      examined whether ratings of PVE predict unique variance in indices of exercise
      related well-being in addition to that explained by satisfaction of the three
      basic psychological needs (for competence, relatedness and autonomy) embedded
      within self-determination theory (SDT). We also examined the extent to which
      variance in perceived variety is empirically distinct from (or subsumed by)
      competence, relatedness and autonomy in the context of exercise. METHODS: A
      convenience sample of community adults (N = 507) completed online surveys twice
      over a six-week period (n = 367). RESULTS: PVE was found to prospectively predict
      unique variance in indices of exercise-related well-being, in addition to that
      explained by perceived competence, relatedness and autonomy. Using exploratory
      and confirmatory factor analytic procedures, perceived variety was found to be
      empirically distinct from perceived competence, relatedness and autonomy.
      CONCLUSION: Results from this work suggest that perceived variety holds potential
      for theoretical and applied advancements in understanding and predicting well
      being in exercise settings.

PMID- 24669788
TI  - Estimation of protein function using template-based alignment of enzyme active
      sites.
AB  - BACKGROUND: The accumulation of protein structural data occurs more rapidly than
      it can be characterized by traditional laboratory means. This has motivated
      widespread efforts to predict enzyme function computationally. The most
      useful/accurate strategies employed to date are based on the detection of motifs
      in novel structures that correspond to a specific function. Functional residues
      are critical components of predictively useful motifs. We have implemented a
      novel method, to complement current approaches, which detects motifs solely on
      the basis of distance restraints between catalytic residues. RESULTS: ProMOL is a
      plugin for the PyMOL molecular graphics environment that can be used to create
      active site motifs for enzymes. A library of 181 active site motifs has been
      created with ProMOL, based on definitions published in the Catalytic Site Atlas
      (CSA). Searches with ProMOL produce better than 50% useful Enzyme Commission (EC)
      class suggestions for level 1 searches in EC classes 1, 4 and 5, and produce some
      useful results for other classes. 261 additional motifs automatically translated
      from Jonathan Barker's JESS motif set [Bioinformatics 19:1644-1649, 2003] and a
      set of NMR motifs is under development. Alignments are evaluated by visual
      superposition, Levenshtein distance and root-mean-square deviation (RMSD) and are
      reasonably consistent with related search methods. CONCLUSION: The ProMOL plugin
      for PyMOL provides ready access to template-based local alignments. Recent
      improvements to ProMOL, including the expanded motif library, RMSD calculations
      and output selection formatting, have greatly increased the program's usability
      and speed, and have improved the way that the results are presented.

PMID- 24669789
TI  - Experience-dependent hemispheric specialization of letters and numbers is
      revealed in early visual processing.
AB  - Recent fMRI research has demonstrated that letters and numbers are preferentially
      processed in distinct regions and hemispheres in the visual cortex. In
      particular, the left visual cortex preferentially processes letters compared with
      numbers, whereas the right visual cortex preferentially processes numbers
      compared with letters. Because letters and numbers are cultural inventions and
      are otherwise physically arbitrary, such a double dissociation is strong evidence
      for experiential effects on neural architecture. Here, we use the high temporal
      resolution of ERPs to investigate the temporal dynamics of the neural
      dissociation between letters and numbers. We show that the divergence between ERP
      traces to letters and numbers emerges very early in processing. Letters evoked
      greater N1 waves (latencies 140-170 msec) than did numbers over left occipital
      channels, whereas numbers evoked greater N1s than letters over the right,
      suggesting letters and numbers are preferentially processed in opposite
      hemispheres early in visual encoding. Moreover, strings of letters, but not
      single letters, elicited greater P2 ERP waves (starting around 250 msec) than
      numbers did over the left hemisphere, suggesting that the visual cortex is tuned
      to selectively process combinations of letters, but not numbers, further along in
      the visual processing stream. Additionally, the processing of both of these
      culturally defined stimulus types differentiated from similar but unfamiliar
      visual stimulus forms (false fonts) even earlier in the processing stream (the P1
      at 100 msec). These findings imply major cortical specialization processes within
      the visual system driven by experience with reading and mathematics. 

PMID- 24669791
TI  - Speculations on the evolution of awareness.
AB  - The "attention schema" theory provides one possible account of the biological
      basis of consciousness, tracing the evolution of awareness through steps from the
      advent of selective signal enhancement about half a billion years ago to the top
      down control of attention, to an internal model of attention (which allows a
      brain, for the first time, to attribute to itself that it has a mind that is
      aware of something), to the ability to attribute awareness to other beings, and
      from there to the human attribution of a rich spirit world surrounding us. Humans
      have been known to attribute awareness to plants, rocks, rivers, empty space, and
      the universe as a whole. Deities, ghosts, souls--the spirit world swirling around
      us is arguably the exuberant attribution of awareness.

PMID- 24669790
TI  - The face of negative affect: trial-by-trial corrugator responses to negative
      pictures are positively associated with amygdala and negatively associated with
      ventromedial prefrontal cortex activity.
AB  - The ability to simultaneously acquire objective physiological measures of emotion
      concurrent with fMRI holds the promise to enhance our understanding of the
      biological bases of affect and thus improve our knowledge of the neural circuitry
      underlying psychiatric disorders. However, the vast majority of neuroimaging
      studies to date examining emotion have not anchored the examination of emotion
      responding circuitry to objective measures of emotional processing. To that end,
      we acquired EMG activity of a valence-sensitive facial muscle involved in the
      frowning response (corrugator muscle) concurrent with fMRI while twenty-six human
      participants viewed negative and neutral images. Trial-by-trial increases in
      corrugator EMG activity to negative pictures were associated with greater
      amygdala activity and a concurrent decrease in ventromedial PFC activity. Thus,
      this study highlights the reciprocal relation between amygdalar and ventromedial
      PFC in the encoding of emotional valence as reflected by facial expression. 

PMID- 24669793
TI  - Multisensory integration during short-term music reading training enhances both
      uni- and multisensory cortical processing.
AB  - The human ability to integrate the input of several sensory systems is essential
      for building a meaningful interpretation out of the complexity of the
      environment. Training studies have shown that the involvement of multiple senses
      during training enhances neuroplasticity, but it is not clear to what extent
      integration of the senses during training is required for the observed effects.
      This study intended to elucidate the differential contributions of uni- and
      multisensory elements of music reading training in the resulting plasticity of
      abstract audiovisual incongruency identification. We used magnetoencephalography
      to measure the pre- and posttraining cortical responses of two randomly assigned
      groups of participants that followed either an audiovisual music reading training
      that required multisensory integration (AV-Int group) or a unisensory training
      that had separate auditory and visual elements (AV-Sep group). Results revealed a
      network of frontal generators for the abstract audiovisual incongruency response,
      confirming previous findings, and indicated the central role of anterior
      prefrontal cortex in this process. Differential neuroplastic effects of the two
      types of training in frontal and temporal regions point to the crucial role of
      multisensory integration occurring during training. Moreover, a comparison of the
      posttraining cortical responses of both groups to a group of musicians that were
      tested using the same paradigm revealed that long-term music training leads to
      significantly greater responses than the short-term training of the AV-Int group
      in anterior prefrontal regions as well as to significantly greater responses than
      both short-term training protocols in the left superior temporal gyrus (STG). 

PMID- 24669794
TI  - Dopamine D2-like receptor activation wipes out preferential consolidation of high
      over low reward memories during human sleep.
AB  - Memory formation is a selective process in which reward contingencies determine
      which memory is maintained and which is forgotten. Sleep plays a pivotal role in
      maintaining information for the long term and has been shown to specifically
      benefit memories that are associated with reward. Key to memory consolidation
      during sleep is a neuronal reactivation of newly encoded representations.
      However, it is unclear whether preferential consolidation of memories associated
      with reward requires the reactivation of dopaminergic circuitry known to mediate
      reward effects at encoding. In a placebo-controlled, double-blind, balanced
      crossover experiment, we show that the dopamine D2-like receptor agonist
      pramipexole given during sleep wipes out reward contingencies. Before sleep, 16
      men learned 160 pictures of landscapes and interiors that were associated with
      high or low rewards, if they were identified between new stimuli at retrieval 24
      hr later. In the placebo condition, the participants retained significantly more
      pictures that promised a high reward. In the pramipexole condition, this
      difference was wiped out, and performance for the low reward pictures was as high
      as that for high reward pictures. Pramipexole did not generally enhance memory
      consolidation probably because of the fact that the dopaminergic agonist
      concurrently suppressed both SWS and REM sleep. These results are consistent with
      the concept that preferential consolidation of reward-associated memories relies
      on hippocampus-driven reactivation within the dopaminergic reward system during
      sleep, whereby during sleep reward contingencies are fed back to the hippocampus
      to strengthen specific memories, possibly, through dopaminergic facilitation of
      long-term potentiation. 

PMID- 24669795
TI  - "Charlie's Lab".

PMID- 24669797
TI  - "It is hardly news that women are oppressed": sexism, activism, and Charlie.

PMID- 24669798
TI  - Travels with Charlie.

PMID- 24669799
TI  - Metropolitan-level ethnic residential segregation, racial identity, and body mass
      index among U.S. Hispanic adults: a multilevel cross-sectional study.
AB  - BACKGROUND: The few studies that have examined whether metropolitan-level ethnic
      residential segregation is associated with obesity among Hispanics are mixed. The
      segmented assimilation theory, which suggests patterns of integration for
      immigrant groups varies by social factors, may provide an explanation for these
      mixed findings. In this study we examined whether one social factor, racial
      identity, modified the association between ethnic residential segregation and
      body mass index (BMI) among Hispanics. METHODS: We used data on 22,901 male and
      37,335 non-pregnant female Hispanic adult participants of the 2003-2008 U.S.
      Behavioral Risk Factor Surveillance System living in 227 metropolitan or
      micropolitan areas (MMSAs). Participants self-identified as White, Black, and
      'some other race'. BMI was calculated using self-reported height and weight; the
      Hispanic isolation index was used to measure Hispanic residential segregation.
      Using multi-level linear regression models, we examined the association of
      Hispanic residential segregation with BMI, and we investigated whether this
      relationship varied by race. RESULTS: Among men, Hispanic segregation was
      unassociated with BMI after adjusting for age, race, MMSA-level poverty, and MMSA
      level population size; there was no variation in this relationship by race. Among
      women, significant associations between Hispanic segregation and BMI in models
      adjusted for demographics and MMSA-level confounders became attenuated with
      further adjustment for education and language of exam. However, there was
      statistically significant variation by race (Pinteraction = 0.03 and 0.09 for
      Hispanic Blacks and Hispanics who identified as some other race, respectively,
      vs. Hispanic Whites). Specifically, higher segregation was associated with higher
      mean BMI among Hispanic Whites, but it was associated with lower mean BMI among
      Hispanic Blacks. Segregation was unassociated with BMI among Hispanic women
      identifying as some other race. CONCLUSIONS: This heterogeneity highlights the
      persistent influence of race on structural processes that can have downstream
      consequences on health. As Hispanics grow as a proportion of the U.S. population,
      especially across urban centers, understanding the health consequences of
      residence in segregated areas, and whether or not these impacts vary across
      different groups, will be important for the design of more comprehensive
      solutions to prevent adverse health outcomes.

PMID- 24669800
TI  - X-ray crystallographic structures of trimers and higher-order oligomeric
      assemblies of a peptide derived from Abeta(17-36).
AB  - A peptide derived from Abeta17-36 crystallizes to form trimers that further
      associate to form higher-order oligomers. The trimers consist of three highly
      twisted beta-hairpins in a triangular arrangement. Two trimers associate face-to
      face in the crystal lattice to form a hexamer; four trimers in a tetrahedral
      arrangement about a central cavity form a dodecamer. These structures provide a
      working model for the structures of oligomers associated with neurodegeneration
      in Alzheimer's disease. 

PMID- 24669801
TI  - Utility values associated with diabetic retinopathy in Chennai, India.
AB  - PURPOSE: The aim of this study was to estimate utility values associated with
      different severity stages of diabetic retinopathy (DR) in India by a direct
      elicitation method (time-trade off, TTO) and indirectly by questionnaire.
      METHODS: People with diabetes aged 40 years and over were recruited from an on
      going DR epidemiology study and a laser clinic in Chennai, India. Utility values
      were elicited using the direct TTO method and indirectly through a validated
      questionnaire (EQ-5D). RESULTS: Of 249 participants, 30 had no DR, 73 had non
      proliferative DR, 114 had sight-threatening DR, and 32 were blind from DR
      (bilateral visual acuity <6/60). The mean TTO utility value was 0.73 (standard
      deviation, SD, 0.31). TTO utility values decreased with increasing severity of DR
      (p < 0.001) and were significantly lower among participants with sight
      threatening DR (0.70, SD 0.33) and blindness (0.55, SD 0.24) compared to those
      with no DR (0.89, SD 0.25) after adjustment for sociodemographic and clinical
      factors. Blindness from DR was independently associated with a lower EQ-5D
      utility value. The utility value derived from EQ-5D (0.06) associated with being
      blind from DR was substantially lower than that of the TTO utility value (0.55).
      CONCLUSIONS: This study provides estimates of utility values that can be used in
      economic evaluations of DR screening strategies in India. The relatively low
      utility values associated with blindness highlights the importance of screening
      programs for early detection of the sight-threatening stages to prevent vision
      loss from DR in this setting.

PMID- 24669802
TI  - Reduced birth weight, cleft palate and preputial abnormalities in a cloned dog.
AB  - The aim of the present study was to report a novel developmental abnormality in a
      cloned dog. A fibroblast cell line was established from an 8-year-old male German
      shepherd dog. In vivo matured oocytes were retrieved from a large breed dog, and
      the nucleus was removed from each oocyte. A donor cell was injected into an
      enucleated oocyte, and the oocyte-cell couplet was fused electrically. After
      chemical activation, the resulting embryos were transferred into a naturally
      estrus-synchronized recipient dog, and two cloned pups were delivered by Cesarean
      section 60 days later. One cloned pup (Clone 1) was healthy, but the other (Clone
      2) had a birth weight of only 320 g and cleft palate, failure of preputial
      closure at the ventral distal part, and persistent penile frenulum. Clone 2 was
      raised by stomach feeding until Day 40 after birth, where palatoplasty was
      performed. The abnormalities in external genitalia in Clone 2 resulted in
      persistent penile extrusion that was surgically corrected. This complex
      developmental abnormality has not been reported in dogs previously.

PMID- 24669803
TI  - Improvement of systolic right ventricular function in overweight children
      participating in a three month football training determined by tricuspid annular
      plane systolic excursion (TAPSE).

PMID- 24669805
TI  - Medical-legal partnerships: collaborating to transform healthcare for vulnerable
      patients-a symposium introduction and overview.

PMID- 24669804
TI  - Thermal dosimetry characteristics of deep regional heating of non-muscle invasive
      bladder cancer.
AB  - PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of
      external deep regional pelvic hyperthermia combined with intravesical mitomycin C
      (MMC) for treating bladder cancer following transurethral resection of bladder
      tumour, and to use thermal data to evaluate reliability of delivering the
      prescribed hyperthermia dose to bladder tissue. MATERIALS AND METHODS: A total of
      14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma
      Ellipse or Sigma 60). The hyperthermia objective was 42 degrees  +/- 2  degrees C
      to bladder tissue for >=40 min per treatment. Temperatures were monitored with
      thermistor probes and recorded values were used to calculate thermal dose and
      evaluate treatment. Anatomical characteristics were examined for possible
      correlations with heating. RESULTS: Combined with BSD-2000 standard treatment
      planning and patient feedback, real-time temperature monitoring allowed thermal
      steering of heat sufficient to attain the prescribed thermal dose to bladder
      tissue within patient tolerance in 91.6% of treatments. Mean treatment time for
      bladder tissue >40  degrees C was 61.9 +/- 11.4 min and mean thermal dose was
      21.3 +/- 16.5 CEM43. Average thermal doses obtained in normal tissues were 1.6 +/
      1.2 CEM43 for the rectum and 0.8 +/- 1.3 CEM43 in superficial normal tissues. No
      significant correlation was seen between patient anatomical characteristics and
      thermal dose achieved in bladder tissue. CONCLUSIONS: This study demonstrates
      that a hyperthermia prescription of 42 degrees  +/- 2  degrees C for 40-60 min
      can be delivered safely to bladder tissue with external radiofrequency phased
      array applicators for a typical range of patient sizes. Using the available
      thermometry and treatment planning, the BSD-2000 hyperthermia system was shown to
      be an effective method of focusing heat regionally around the bladder with good
      patient tolerance.

PMID- 24669806
TI  - Obligation and opportunity: medical-legal partnership in the age of health
      reform.

PMID- 24669807
TI  - Investing in legal prevention: connecting access to civil justice and healthcare
      through medical-legal partnership.

PMID- 24669808
TI  - The MLP vital sign: assessing and managing legal needs in the healthcare setting.

PMID- 24669809
TI  - The health law partnership: a medical-legal partnership strategically designed to
      provide a coordinated approach to public health legal services, education,
      advocacy, evaluation, research, and scholarship.

PMID- 24669810
TI  - Rural health systems and legal care: opportunities for initiating and maintaining
      legal care after the Patient Protection and Affordable Care Act.

PMID- 24669811
TI  - Educating the next generation of health leaders: medical-legal partnership and
      interprofessional graduate education.

PMID- 24669812
TI  - Medical-legal partnership in medical education: pathways and opportunities.

PMID- 24669813
TI  - Blueprint for success: translating innovations from the field of palliative
      medicine to the medical-legal partnership.

PMID- 24669814
TI  - Medical-legal partnership and healthy start: integrating civil legal aid services
      into public health advocacy.

PMID- 24669815
TI  - H2Whoa?!: an examination of the presence of pharmaceuticals in America's waters.

PMID- 24669816
TI  - Low temperature kinetics of the CH3OH + OH reaction.
AB  - The rate constant of the reaction between methanol and the hydroxyl radical has
      been studied in the temperature range 56-202 K by pulsed laser photolysis-laser
      induced fluorescence in two separate experiments using either a low temperature
      flow tube coupled to a time-of-flight mass spectrometer or a pulsed Laval nozzle
      apparatus. The two independent techniques yield rate constants that are in mutual
      agreement and consistent with the results reported previously below 82 K [Shannon
      et al. Nat. Chem. 2013, 5, 745-749] and above 210 K [Dillon et al. Phys. Chem.
      Chem. Phys. 2005, 7, 349-355], showing a very sharp increase with decreasing
      temperature with an onset around 180 K. This onset is also signaled by strong
      chemiluminescence tentatively assigned to formaldehyde, which is consistent with
      the formation of the methoxy radical at low temperature by quantum tunnelling,
      and its subsequent reaction with H and OH. Our results add confidence to the
      previous low temperature rate constant measurements and consolidate the
      experimental reference data set for further theoretical work required to describe
      quantitatively the tunnelling mechanism operating in this reaction. An additional
      measurement of the rate constant at 56 K yielded a value of (4.9 +/- 0.8) * 10(
      11) cm(3) molecule(-1) s(-1) (2sigma), showing that the rate constant is
      increasing less rapidly at temperatures below 70 K. 

PMID- 24669818
TI  - Asymmetric dimethylarginine levels in patients with cutaneous anthrax: a
      laboratory analysis.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), the main endogenous inhibitor of
      nitric oxide synthase, is considered to be associated with endothelial
      dysfunction. High ADMA levels have been shown to be related with disorders
      causing vascular inflammation such as hypertension, hypercholesterolemia,
      atherosclerosis, chronic heart failure, stroke and sepsis. Cutaneous anthrax (CA)
      is a serious infectious disease which may cause vasculitis. The aim of the study
      was to investigate the serum ADMA levels in patients with CA. METHODS: A total of
      35 serum samples of the patients with CA and 18 control sera were tested for ADMA
      levels using ADMA ELISA kit (Immunodiagnostik AG, Bensheim, Germany). RESULTS:
      ADMA levels were found to be significantly higher in the patients group than the
      controls (p < 0.001). In addition, ADMA levels were found to be positively
      associated with sedimentation rates (R = 0.413; p = 0.026), and inversely
      associated with international normalized ratio (INR) levels (R = -0.46; p =
      0.011). A cut-off value of 0.475 of ADMA had a sensitivity of 74.3%, specificity
      of 77.8%, and accuracy of 75.5% in the diagnosis of CA. CONCLUSION: Although the
      exact mechanism still remains unclear, ADMA levels could be related to immune
      activation in CA. In addition, these data might suggest the higher ADMA levels in
      patients could be due to the perivascular inflammation and vasculitis in CA.

PMID- 24669817
TI  - A genomic signature approach to rescue DeltaF508-cystic fibrosis transmembrane
      conductance regulator biosynthesis and function.
AB  - The most common cystic fibrosis (CF) mutation, DeltaF508, causes protein
      misfolding, leading to proteosomal degradation. We recently showed that
      expression of miR-138 enhances CF transmembrane conductance regulator (CFTR)
      biogenesis and partially rescues DeltaF508-CFTR function in CF airway epithelia.
      We hypothesized that a genomic signature approach can be used to identify new
      bioactive small molecules affecting DeltaF508-CFTR rescue. The Connectivity Map
      was used to identify 27 small molecules with potential to restore DeltaF508-CFTR
      function in airway epithelia. The molecules were screened in vitro for efficacy
      in improving DeltaF508-CFTR trafficking, maturation, and chloride current. We
      identified four small molecules that partially restore DeltaF508-CFTR function in
      primary CF airway epithelia. Of these, pyridostigmine showed cooperativity with
      corrector compound 18 in improving DeltaF508-CFTR function. There are few CF
      therapies based on new molecular insights. Querying the Connectivity Map with
      relevant genomic signatures offers a method to identify new candidates for
      rescuing DeltaF508-CFTR function. 

PMID- 24669819
TI  - An evidence based systematic review of remifentanil associated opioid-induced
      hyperalgesia.
AB  - INTRODUCTION: Therapeutic opioid use continues to grow, with greater than a
      fivefold increase in usage of fentanyl-based products over a 10-year period.
      Opioids are known for their side-effect profile, including bradycardia and
      respiratory depression; questions remain, however, regarding lesser known side
      effects such as opioid-induced hyperalgesia (OIH). AREAS COVERED: A systematic
      review of published literature addressing remifentanil OIH in the surgical
      setting was completed. A search was conducted of PubMed, Embase and Ovid from
      1946 until June 2013. Inclusion criteria consisted of age >= 18 years, humans,
      full-text articles and English language. A total of 35 unique articles were
      included. Sixteen articles reported outcomes that supported remifentanil OIH and
      6 that refuted and 22 were focused on prevention. EXPERT OPINION: There is
      conflicting evidence regarding the existence of remifentanil OIH. Outcomes
      evaluating measures of hyperalgesia frequently conclude that remifentanil OIH
      exists, while those evaluating opioid consumption do not. Therefore, remifentanil
      does induce a degree of hyperalgesia, but we do not believe that it reaches a
      level of clinical significance that requires prevention. If a significant concern
      for the development of remifentanil OIH is suspected, we suggest using the least
      possible effective dose of remifentanil as the primary prevention strategy.

PMID- 24669821
TI  - Amorphization strategy affects the stability and supersaturation profile of
      amorphous drug nanoparticles.
AB  - Amorphous drug nanoparticles have recently emerged as a promising bioavailability
      enhancement strategy of poorly soluble drugs attributed to the high
      supersaturation solubility generated by the amorphous state and fast dissolution
      afforded by the nanoparticles. Herein we examine the effects of two amorphization
      strategies in the nanoscale, i.e., (1) molecular mobility restrictions and (2)
      high energy surface occupation, both by polymer excipient stabilizers, on the (i)
      morphology, (ii) colloidal stability, (iii) drug loading, (iv) amorphous state
      stability after three-month storage, and (v) in vitro supersaturation profiles,
      using itraconazole (ITZ) as the model drug. Drug-polyelectrolyte complexation is
      employed in the first strategy to prepare amorphous ITZ nanoparticles using
      dextran sulfate as the polyelectrolyte (ITZ nanoplex), while the second strategy
      employs pH-shift precipitation using hydroxypropylmethylcellulose as the surface
      stabilizer (nano-ITZ), with both strategies resulting in >90% ITZ utilization.
      Both amorphous ITZ nanoparticles share similar morphology (~300 nm spheres) with
      the ITZ nanoplex exhibiting better colloidal stability, albeit at lower ITZ
      loading (65% versus 94%), due to the larger stabilizer amount used. The ITZ
      nanoplex also exhibits superior amorphous state stability, attributed to the ITZ
      molecular mobility restriction by electrostatic complexation with dextran
      sulfate. The higher stability, however, is obtained at the expense of slower
      supersaturation generation, which is maintained over a prolonged period, compared
      to the nano-ITZ. The present results signify the importance of selecting the
      optimal amorphization strategy, in addition to formulating the excipient
      stabilizers, to produce amorphous drug nanoparticles having the desired
      characteristics. 

PMID- 24669820
TI  - Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF
      kappaB signaling pathway in experimental traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade
      that contributes to substantial neuronal damage and behavioral impairment, and
      Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the
      current study, we tested the hypothesis that curcumin, a phytochemical compound
      with potent anti-inflammatory properties that is extracted from the rhizome
      Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following
      TBI. METHODS: Neurological function, brain water content and cytokine levels were
      tested in TLR4-/- mice subjected to weight-drop contusion injury. Wild-type (WT)
      mice were injected intraperitoneally with different concentrations of curcumin or
      vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of
      microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal
      apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by
      ELISA; and TLR4, MyD88 and NF-kappaB levels were measured by Western blotting. In
      vitro, a co-culture system comprised of microglia and neurons was treated with
      curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and
      morphological activation in microglia and morphological damage to neurons were
      detected by immunohistochemistry 24 hours post-stimulation. RESULTS: The protein
      expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post
      TBI. Compared with WT mice, TLR4-/- mice showed attenuated functional impairment,
      brain edema and cytokine release post-TBI. In addition to improvement in the
      above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the
      number of TLR4-positive microglia/macrophages as well as inflammatory mediator
      release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis
      indicated that the levels of TLR4 and its known downstream effectors (MyD88, and
      NF-kappaB) were also decreased after curcumin treatment. Similar outcomes were
      observed in the microglia and neuron co-culture following treatment with curcumin
      after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological
      activation in microglia and increased neuronal apoptosis, whereas curcumin
      normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF
      kappaB in microglia were attenuated by curcumin treatment. CONCLUSIONS: Our
      results suggest that post-injury, curcumin administration may improve patient
      outcome by reducing acute activation of microglia/macrophages and neuronal
      apoptosis through a mechanism involving the TLR4/MyD88/NF-kappaB signaling
      pathway in microglia/macrophages in TBI.

PMID- 24669822
TI  - Lipid nanotube formation using space-regulated electric field above
      interdigitated electrodes.
AB  - Lipid nanotubes have great potential in biology and nanotechnology. Here we
      demonstrate a method to form lipid nanotubes using space-regulated AC electric
      fields above coplanar interdigitated electrodes. The AC electric field
      distribution can be regulated by solution height above the electrodes. The ratio
      of field component in x axis (Ex) to field component in z axis (Ez) increases
      dramatically at solution height below 50 MUm; therefore, at lower solution
      height, the force from Ex predominantly drives lipids to form lipid nanotubes
      along with the electric field direction. The forces exerted on the lipid nanotube
      during its formation were analyzed in detail, and an equation was obtained to
      describe the relationship among nanotube length and field frequency, amplitude,
      and time. We believe that the presented approach opens a way to design and
      prepare nanoscale materials with unique structural and functional properties
      using space-regulated electric fields. 

PMID- 24669823
TI  - Association of N-glycosylation with breast carcinoma and systemic features using
      high-resolution quantitative UPLC.
AB  - An improved separation of the human serum N-glycome using hydrophilic interaction
      chromatography technology with UPLC is described, where more than 140 N-glycans
      were assigned. Using this technique, serum samples from 107 healthy controls and
      62 newly diagnosed breast cancer patients were profiled. The most statistically
      significant alterations were observed in cancer patients compared with healthy
      controls: an increase in sialylation, branching, and outer-arm fucosylation and a
      decrease in high-mannosylated and biantennary core-fucosylated glycans. In the
      controls and cases combined systemic features were analyzed; serum estradiol was
      associated with increase in digalactosylated glycans, and higher mammographic
      density was associated with increase in biantennary digalactosylated glycans and
      with decrease in trisialylated and in outer-arm fucosylated glycans. Furthermore,
      particular glycans were altered in some features of the breast carcinomas;
      bisected biantennary nonfucosylated glycans were decreased in patients with
      progesterone receptor positive tumors, and core-fucosylated biantennary bisected
      monogalactosylated glycans were decreased in patients with the TP53 mutation.
      Systemic features show more significant associations with the serum N-glycome
      than do the features of the breast carcinomas. In conclusion, the UPLC-based
      glycan analysis technique described here reveals highly significant differences
      between healthy women and breast cancer patients. Significant associations with
      breast carcinoma and systemic features are described. 

PMID- 24669824
TI  - Use of complementary and alternative medicine by older adults--a cross-sectional
      survey.
AB  - BACKGROUND: Very little is known about complementary and alternative medicine
      (CAM) use by older adults in Germany. The aim of this study was to investigate
      the use of CAM and other health promoting substances (e.g., herbal teas) by older
      adults of at least 70 years of age. METHODS: A cross-sectional questionnaire
      study was conducted among persons of >=70 years from metropolitan Berlin and
      rural parts of Brandenburg, Germany. Recorded were: demographics, current use of
      CAM, medical diagnoses, users' opinions and preferences. RESULTS: A total of 400
      older adults, living as 'self-reliant' (n = 154), 'home care service user' (n =
      97), or 'in nursing home' (n = 149), and with the legal status 'without guardian'
      (n = 355) or 'with guardian' (n = 45) were included (mean age 81.8 +/- 7.4 years,
      78.5% female). Any type of CAM used 61.3% of respondents (dietary supplements
      35.5%, herbal medicines 33.3%, and external preparations 26.8%); 3.0% used drug
      interaction causing preparations. Usage was based on recommendations (total
      30.3%; in 20.0% by friends or family and 10.4% by pharmacists), own initiative
      (27.3%), and doctors' prescription (25.8%). Participants with legal guardian took
      almost solely prescribed dietary supplements. Of the others, only half (58.7%)
      informed their general practitioner (GP) of their CAM use. Participants expected
      significant (44.9%) or moderate (37.1%) improvement; half of them perceived a
      good effect (58.7%) and two-thirds (64.9%) generally preferred a combination of
      CAM and conventional medicine. More than half (57.9%) stated that they could
      neither assess whether their CAM preparations have side effects, nor assess what
      the side effects might be. Strongest predictors for CAM use were two treatment
      preferences (vs. 'conventional only': 'CAM only', OR = 3.98, p = 0.0042 and 'CAM
      + conventional', 3.02, 0.0028) and the type of health insurance ('statutory' vs.
      'private', 3.57, 0.0356); against CAM use two subjective assessments predicted
      (vs. 'CAM causes no harm': 'CAM causes harmful drug interactions', 0.25, 0.0536
      and 'I cannot assess side effects', 0.28, 0.0010). CONCLUSION: Older German
      adults frequently use CAM. They perceived it as an effective complement to
      conventional medicine, but are not sufficiently informed about risks and
      benefits.

PMID- 24669825
TI  - Comparison between two protocols for thawed embryo transfer: natural cycle versus
      exogenous hormone replacement.
AB  - INTRODUCTION: There are two most popular protocols for Frozen Embryo Transfer:
      the natural and the E2&P4 replacement cycles. There is still a controversy
      whether one is superior over the other. PURPOSE: To compare the outcome in
      patient groups undergoing FET following these protocols. METHODS: About 1235 FET
      cycles were retrospectively analyzed during a period of 12 years. In 798 cycles
      (group A), the natural cycle protocol was used, and in 437 cycles (group B), the
      exogenous E2&P4 administration protocol was used. RESULTS: The average patient
      age was 32.11 +/- 0.27 years in group A and 32.94 +/- 0.19 years in group B
      (p<0.05). The endometrial thickness was 9.54 +/- 0.11 mm and 8.95 +/- 0.13 mm in
      groups A and B, respectively (p<0.001). The peak serum E2 level was 162.51 +/-
      8.97 pg/mL and 250.78 +/- 33.67 pg/mL in groups A and B, respectively (p<0.001).
      The implantation, clinical pregnancy, and ongoing pregnancy rates in groups A and
      B were 6.47%, 12.91%, and 10.4% versus 4.26%, 8.47%, and 5.95%, respectively
      (p<0.05). CONCLUSIONS: Natural endometrial preparation yields better outcome in
      compare with exogenous E2&P4 in FET cycles with higher endometrial thickness,
      implantation, and clinical pregnancy rates.

PMID- 24669826
TI  - Testing for association of the monoamine oxidase A promoter polymorphism with
      brain structure volumes in both autism and the fragile X syndrome.
AB  - BACKGROUND: Autism and the fragile X syndrome (FXS) are related to each other
      genetically and symptomatically. A cardinal biological feature of both disorders
      is abnormalities of cerebral cortical brain volumes. We have previously shown
      that the monoamine oxidase A (MAOA) promoter polymorphism is associated with
      cerebral cortical volumes in children with autism, and we now sought to determine
      whether the association was also present in children with FXS. METHODS:
      Participants included 47 2-year-old Caucasian boys with FXS, some of whom also
      had autism, as well as 34 2-year-old boys with idiopathic autism analyzed in a
      previous study. The MAOA promoter polymorphism was genotyped and tested for
      relationships with gray and white matter volumes of the cerebral cortical lobes
      and cerebro-spinal fluid volume of the lateral ventricles. RESULTS: MAOA genotype
      effects in FXS children were the same as those previously observed in idiopathic
      autism: the low activity MAOA promoter polymorphism allele was associated with
      increased gray and white matter volumes in all cerebral lobes. The effect was
      most pronounced in frontal lobe gray matter and all three white matter regions:
      frontal gray, F = 4.39, P = 0.04; frontal white, F = 5.71, P = 0.02; temporal
      white, F = 4.73, P = 0.04; parieto-occipital white, F = 5.00, P = 0.03. Analysis
      of combined FXS and idiopathic autism samples produced P values for these regions
      <0.01 and effect sizes of approximately 0.10. CONCLUSIONS: The MAOA promoter
      polymorphism is similarly associated with brain structure volumes in both
      idiopathic autism and FXS. These data illuminate a number of important aspects of
      autism and FXS heritability: a genetic effect on a core biological trait of
      illness, the specificity/generalizability of the genetic effect, and the utility
      of examining individual genetic effects on the background of a single gene
      disorder such as FXS.

PMID- 24669827
TI  - Prevalence and antimicrobial resistance among Gram-negative pathogens in Saudi
      Arabia.
AB  - Antimicrobial resistance among Gram-negative bacteria is a worldwide problem,
      including in the Kingdom of Saudi Arabia, with major concerns regarding
      Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. Although
      over half of the isolates of P. aeruginosa remain susceptible to carbapenems,
      quinolones, and aminoglycosides in most reports from Saudi Arabia, resistance is
      on increase, with a worrying high prevalence of multidrug resistance.
      Ceftazidime, ciprofloxacin, and aminoglycosides remain active against A.
      baumannii isolates in some studies from the Kingdom, but recent data suggest
      increased resistance. Carbapenems are now the treatment of choice for
      Acinetobacter infections but their activity too is being eroded. Among
      Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, and Enterobacter
      spp. are the most clinically relevant species. Rates of extended-spectrum beta
      lactamase (ESBL) production by these species vary among studies but are generally
      high in Saudi Arabia, with many ESBL-producing isolates multiresistant to other
      agents, except carbapenems and nitrofurantoin. A similar pattern is seen for
      Klebsiella, although with more resistance to quinolones, aminoglycosides, and to
      nitrofurantoin than in E. coli. Enterobacter is commonly resistant to
      penicillins, monobactams, and cephalosporins but mostly susceptible to
      carbapenems. Carbapenemases are beginning to emerge in Enterobacteriaceae. 

PMID- 24669828
TI  - Multi-model inference using mixed effects from a linear regression based genetic
      algorithm.
AB  - BACKGROUND: Different high-dimensional regression methodologies exist for the
      selection of variables to predict a continuous variable. To improve the variable
      selection in case clustered observations are present in the training data, an
      extension towards mixed-effects modeling (MM) is requested, but may not always be
      straightforward to implement.In this article, we developed such a MM extension
      (GA-MM-MMI) for the automated variable selection by a linear regression based
      genetic algorithm (GA) using multi-model inference (MMI). We exemplify our
      approach by training a linear regression model for prediction of resistance to
      the integrase inhibitor Raltegravir (RAL) on a genotype-phenotype database, with
      many integrase mutations as candidate covariates. The genotype-phenotype pairs in
      this database were derived from a limited number of subjects, with presence of
      multiple data points from the same subject, and with an intra-class correlation
      of 0.92. RESULTS: In generation of the RAL model, we took computational
      efficiency into account by optimizing the GA parameters one by one, and by using
      tournament selection. To derive the main GA parameters we used 3 times 5-fold
      cross-validation. The number of integrase mutations to be used as covariates in
      the mixed effects models was 25 (chrom.size). A GA solution was found when R2MM >
      0.95 (goal.fitness). We tested three different MMI approaches to combine the
      results of 100 GA solutions into one GA-MM-MMI model. When evaluating the GA-MM
      MMI performance on two unseen data sets, a more parsimonious and interpretable
      model was found (GA-MM-MMI TOP18: mixed-effects model containing the 18 most
      prevalent mutations in the GA solutions, refitted on the training data) with
      better predictive accuracy (R2) in comparison to GA-ordinary least squares (GA
      OLS) and Least Absolute Shrinkage and Selection Operator (LASSO). CONCLUSIONS: We
      have demonstrated improved performance when using GA-MM-MMI for selection of
      mutations on a genotype-phenotype data set. As we largely automated setting the
      GA parameters, the method should be applicable on similar datasets with clustered
      observations.

PMID- 24669830
TI  - Perylenediimide-based donor-acceptor dyads and triads: impact of molecular
      architecture on self-assembling properties.
AB  - Perylenediimide-based donor-acceptor co-oligomers are particularly attractive in
      plastic electronics because of their unique electro-active properties that can be
      tuned by proper chemical engineering. Herein, a new class of co-oligomers has
      been synthesized with a dyad structure (AD) or a triad structure (DAD and ADA) in
      order to understand the correlations between the co-oligomer molecular
      architecture and the structures formed by self-assembly in thin films. The
      acceptor block A is a perylene tetracarboxyl diimide (PDI), whereas the donor
      block D is made of a combination of thiophene, fluorene, and 2,1,3
      benzothiadiazole derivatives. D and A blocks are linked by a short and flexible
      ethylene spacer to ease self-assembling in thin films. Structural studies using
      small and wide X-ray diffraction and transmission electron microscopy demonstrate
      that AD and ADA lamellae are made of a double layer of co-oligomers with
      overlapping and strongly pi-stacked PDI units because the sectional area of the
      PDI is about half that of the donor block. These structural models allow
      rationalizing the absence of organization for the DAD co-oligomer and therefore
      to draw general rules for the design of PDI-based dyads and triads with proper
      self-assembling properties of use in organic electronics. 

PMID- 24669829
TI  - Transient paradoxical bronchospasm associated with inhalation of the LAMA
      AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled
      studies.
AB  - BACKGROUND: AZD9164 has demonstrated potential as an inhaled, long-acting,
      muscarinic antagonist (LAMA) bronchodilator. However, in patients with COPD, but
      not in healthy subjects, a transient initial drop in FEV1 was observed following
      inhalation of nebulised doses of AZD9164 in citrate buffer.Two additional studies
      were conducted to further assess the safety and tolerability of multiple
      ascending doses of AZD9164 in 27 white and 18 Japanese healthy subjects and in 4
      patients with COPD. In these studies, AZD9164 was inhaled via TurbuhalerTM.
      METHODS: These were Phase I, randomised, double-blind, placebo-controlled,
      multiple ascending dose (MAD) studies conducted in Sweden and UK. Healthy
      subjects (mean age 25.9 yrs) and patients with COPD (mean age 66 yrs, mean post
      bronchodilator FEV1 60.1% predicted normal value) were randomised 2:1 to active
      treatment (400, 1000 or 2800 MUg delivered doses of AZD9164) or placebo. RESULTS:
      No safety or tolerability concerns were identified in the healthy subjects at
      doses up to and including 2800 MUg and both studies confirmed the bronchodilator
      effect of AZD9164. However, the first 3 patients in the COPD cohort who received
      AZD9164 (1000 MUg) experienced a transient fall in FEV1 5 to 15 minutes after
      inhalation of AZD9164 while the patient receiving placebo did not. The study
      safety review process then resulted in cessation of further activities on
      AZD9164. Retrospective analysis showed that two healthy subjects had also had
      transient falls in FEV1 shortly after inhalation of AZD9164 400 and 2800 MUg
      respectively, although neither reported any related respiratory symptoms or other
      AEs. CONCLUSIONS: These results show that transient paradoxical
      bronchoconstriction can occur in some healthy subjects, in addition to patients
      with COPD, following inhalation of AZD9164 and that the citrate buffer used in
      the nebulised formulation cannot have been the only cause of the drop in FEV1 in
      previous studies. As preclinical data do not provide an explanation, the reasons
      for this brief post-dose drop in FEV1 remain unclear. However, these results
      highlight the importance of monitoring lung function immediately post-dose when
      investigating novel inhaled treatments, even when a rapid onset of effect is not
      expected. TRIAL REGISTRATION: Clinicaltrials.gov NCT01016951 and NCT01096563.

PMID- 24669832
TI  - Low-Dose Radiation Risks of Computerized Tomography and Cone Beam Computerized
      Tomography: Reducing the Fear and Controversy.
AB  - Regulations for protecting humans against stochastic biological effects from
      ionizing radiation are based on the linear no-threshold (LNT) risk assessment
      model, which states that any amount of radiation exposure may lead to cancer in a
      population. Based on the LNT model, risk from low-dose radiation increases
      linearly with increasing doses of radiation. Imaging procedures in medicine and
      dentistry are an important source of low-dose ionizing radiation. The increased
      use of computerized tomography (CT) and cone beam computerized tomography (CBCT)
      has raised health concerns regarding exposure to low-dose ionizing radiation. In
      oral and maxillofacial surgery and implant dentistry, CBCT is now at the
      forefront of this controversy. Although caution has been expressed, there have
      been no direct studies linking radiation exposure from CT and CBCT used in dental
      imaging with cancer induction. This article describes the concerns about
      radiation exposure in dental imaging regarding the use of CT. 

PMID- 24669831
TI  - An inhibitor's-eye view of the ATP-binding site of CDKs in different regulatory
      states.
AB  - We have used a chemically diverse panel of kinase inhibitors to assess the
      chemical similarity of the ATP-binding sites of cyclin-dependent kinase (CDK)
      subfamily members in a range of activation states. Using this approach, we find
      that different activation states of a particular CDK may differ from each other
      as much as different CDKs in the same activation state. We also find that
      inhibitors discriminate more effectively among CDK family members in their
      monomeric state than in their cyclin-bound state, providing direct evidence for
      the belief that selective binding to inactive kinase states might be more readily
      achieved than selective binding to active states.

PMID- 24669833
TI  - What's the message? A content analysis of newspaper articles about assisted
      reproductive technology from 2005 to 2011.
AB  - Infertility and its treatment is the subject of considerable media coverage. In
      order to evaluate the representation of assisted reproductive technology (ART) in
      the popular media, we conducted a content analysis of North American newspaper
      articles. We also explored whether different themes emerged in relation to the
      implementation of public funding for ART in Quebec, Canada. Print and online
      newspaper articles from 2005 to 2011 were retrieved using the terms "in-vitro
      fertilization", "infertility treatment", "assisted reproductive technology", and
      "IVF treatment". Totally, 719 newspaper articles met inclusion criteria and were
      coded according to predetermined categories. Risks (63%) and ethical issues (61%)
      related to ART were most commonly featured. Quebec-based articles were mostly
      concerned with the politics and financial issues governing ART, and were less
      likely to report the risks and emotional impact of ART than other North American
      press. Newspapers tended to emphasize extreme scenarios as well as controversial
      cases that may not represent the everyday realities of ART. Changes in public
      policy may also engender shifts in the tone and content of media reports. It is
      important to establish resources that can inform the public as well as
      prospective infertility patients about their condition and potential treatment
      options.

PMID- 24669834
TI  - Acute and sub-acute effects of repetitive kicking on hip adduction torque in
      injury-free elite youth soccer players.
AB  - Hip adduction strength is important for kicking and acceleration in soccer
      players. Changes in hip adduction strength may therefore have an effect on soccer
      players' athletic performance. The purpose of this study was to investigate the
      acute and sub-acute effects of a kicking drill session on hip strength,
      concerning isometric hip adduction, abduction and flexion torque of the kicking
      leg and the supporting leg. Ten injury-free male elite soccer players, mean +/- s
      age of 15.8 +/- 0.4 years participated. All players underwent a specific 20 min
      kicking drill session, comprising 45 kicks. The players were tested the day
      before, 15 min after and 24 h after the kicking drill session by a blinded tester
      using a reliable test procedure. The isometric hip-action and leg-order were
      randomized. For the kicking leg, hip adduction torque increased from 2.45 (2.19
      2.65) Nm ? kg(-1), median (25th-75th percentiles), at pre-kicking to 2.65 (2.55
      2.81) Nm ? kg(-1) (P = 0.024) 24 h post-kicking. This may have implications for
      the soccer player's ability to maximally activate the hip adductors during
      kicking and acceleration, and thereby improve performance the day after a kicking
      drill session.

PMID- 24669835
TI  - An algebra-based method for inferring gene regulatory networks.
AB  - BACKGROUND: The inference of gene regulatory networks (GRNs) from experimental
      observations is at the heart of systems biology. This includes the inference of
      both the network topology and its dynamics. While there are many algorithms
      available to infer the network topology from experimental data, less emphasis has
      been placed on methods that infer network dynamics. Furthermore, since the
      network inference problem is typically underdetermined, it is essential to have
      the option of incorporating into the inference process, prior knowledge about the
      network, along with an effective description of the search space of dynamic
      models. Finally, it is also important to have an understanding of how a given
      inference method is affected by experimental and other noise in the data used.
      RESULTS: This paper contains a novel inference algorithm using the algebraic
      framework of Boolean polynomial dynamical systems (BPDS), meeting all these
      requirements. The algorithm takes as input time series data, including those from
      network perturbations, such as knock-out mutant strains and RNAi experiments. It
      allows for the incorporation of prior biological knowledge while being robust to
      significant levels of noise in the data used for inference. It uses an
      evolutionary algorithm for local optimization with an encoding of the
      mathematical models as BPDS. The BPDS framework allows an effective
      representation of the search space for algebraic dynamic models that improves
      computational performance. The algorithm is validated with both simulated and
      experimental microarray expression profile data. Robustness to noise is tested
      using a published mathematical model of the segment polarity gene network in
      Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with
      a spectrum of state-of-the-art network inference methods on data from the
      synthetic IRMA network to demonstrate that our method has good precision and
      recall for the network reconstruction task, while also predicting several of the
      dynamic patterns present in the network. CONCLUSIONS: Boolean polynomial
      dynamical systems provide a powerful modeling framework for the reverse
      engineering of gene regulatory networks, that enables a rich mathematical
      structure on the model search space. A C++ implementation of the method,
      distributed under LPGL license, is available, together with the source code, at
      http://www.paola-vera-licona.net/Software/EARevEng/REACT.html.

PMID- 24669837
TI  - Sox2 regulates the emergence of lung basal cells by directly activating the
      transcription of Trp63.
AB  - Lung development is determined by the coordinated expression of several key
      genes. Previously, we and others have shown the importance of the sex determining
      region Y-box 2 (Sox2) gene in lung development. Transgenic expression of Sox2
      during lung development resulted in cystic airways, and here we show that
      modulating the timing of ectopic Sox2 expression in the branching regions of the
      developing lung results in variable cystic lesions resembling the spectrum of the
      human congenital disorder congenital cystic adenomatoid malformation (CCAM). Sox2
      dominantly differentiated naive epithelial cells into the proximal lineage
      irrespective of the presence of Fgf10. Sox2 directly induced the expression of
      Trp63, the master switch toward the basal cell lineage and induced the expression
      of Gata6, a factor involved in the emergence of bronchoalveolar stem cells. We
      showed that SOX2 and TRP63 are coexpressed in the lungs of human patients with
      type II CCAM. The combination of premature differentiation toward the proximal
      cell lineage and the induction of proliferation resulted in the cyst-like
      structures. Thus, we show that Sox2 is directly responsible for the emergence of
      two lung progenitor cells: basal cells by regulating the master gene Trp63 and
      bronchoalveolar stem cells by regulating Gata6. 

PMID- 24669838
TI  - On the Internet of Things, smart cities and the WHO Healthy Cities.
AB  - This article gives a brief overview of the Internet of Things (IoT) for cities,
      offering examples of IoT-powered 21st century smart cities, including the
      experience of the Spanish city of Barcelona in implementing its own IoT-driven
      services to improve the quality of life of its people through measures that
      promote an eco-friendly, sustainable environment. The potential benefits as well
      as the challenges associated with IoT for cities are discussed. Much of the 'big
      data' that are continuously generated by IoT sensors, devices, systems and
      services are geo-tagged or geo-located. The importance of having robust,
      intelligent geospatial analytics systems in place to process and make sense of
      such data in real time cannot therefore be overestimated. The authors argue that
      IoT-powered smart cities stand better chances of becoming healthier cities. The
      World Health Organization (WHO) Healthy Cities Network and associated national
      networks have hundreds of member cities around the world that could benefit from,
      and harness the power of, IoT to improve the health and well-being of their local
      populations. 

PMID- 24669839
TI  - The safety of novel drugs used to treat irritable bowel syndrome.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI)
      disorder with a high prevalence. Besides efficacy, the safety of each drugs used
      to treat GI disorders is an important issue in the drug development process.
      AREAS COVERED: This article reviews all Phase I to IV clinical trials or case
      reports with results related to the safety of novel GI drugs. The drugs are
      currently approved or under evaluation for approval. EXPERT OPINION: Most of the
      reported adverse events were related to the GI tract with mild-to-moderate
      severity. Diarrhea was significantly higher versus placebo following use of
      linaclotide and renzapride, similar to that of constipation with ramosetron.
      Lubiprostone, linaclotide and rifaximin with low systemic bioavailability have
      less adverse events and exert more advantageous results. Asimadoline acts
      peripherally on kappa-opioid receptors and is not associated with CNS side
      effects. As lubiprostone and linaclotide cause dose-dependent adverse events,
      starting the treatment with the lowest effective doses is advised. Ramosetron is
      under evaluation for diarrhea-predominant IBS due to its acceptable safety and
      tolerability, besides its efficacy. Rifaximin, asimadoline and renzapride are
      still in need of more long-term studies regarding their safety.

PMID- 24669840
TI  - Benefits of NOPO as chelator in gallium-68 peptides, exemplified by preclinical
      characterization of (68)Ga-NOPO-c(RGDfK).
AB  - The alphavbeta3-integrin addressing cyclic pentapeptide cyclo(RGDfK) was
      conjugated to NOPO, 1,4,7-triazacyclononane-1,4
      bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2
      carboxyethyl)phosphinic acid], a bifunctional chelator with exceptional gallium
      68 labeling properties. NOPO-c(RGDfK) and its Ga(III) and Cu(II) complexes showed
      high affinity to alphavbeta3 integrin (IC50 = 0.94 +/- 0.06, 1.02 +/- 0.09, and
      0.51 +/- 0.06 nM, respectively). (68)Ga labeling of NOPO-c(RGDfK) in an automated
      GMP-compliant procedure was performed with near-quantitative radiochemical yield,
      using precursor amounts as low as 0.5 nmol (approximately 0.6 MUg). (68)Ga-NOPO
      c(RGDfK) was obtained with high purity (>99% by radio-HPLC/TLC) and, optionally,
      could be produced with specific activities up to 6 TBq/MUmol. M21/M21L (human
      melanoma with high/low alphavbeta3 integrin expression) xenografted athymic CD-1
      nude mice were used for biodistribution, in vivo stability studies, and PET
      imaging. (68)Ga-NOPO-c(RGDfK) showed rapid and specific uptake in M21 tumor
      xenografts (2.02 +/- 0.34% ID/g at 60 min p.i.) and was found stable in vivo. Its
      high hydrophilicity is reflected by an octanol-water distribution coefficient
      (log D = -4.6) which is more than 1 order of magnitude lower compared to
      respective NOTA or DOTA analogues. As expected, (68)Ga-NOPO-c(RGDfK) thus showed
      fast renal clearance from nontargeted tissues. We conclude that NOPO might
      generally prove a useful means to improve renal clearance of corresponding
      radiopharmaceuticals by increasing the polarity of its bioconjugates. Favorable
      labeling properties render NOPO conjugates highly recommendable for reliable
      routine production of (68)Ga-radiopharmaceuticals in a clinical setting. 

PMID- 24669841
TI  - Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a
      case series.
AB  - BACKGROUND: Invasive fungal infections are very severe infections associated with
      high mortality rates, despite the availability of new classes of antifungal
      agents. Based on pathophysiological mechanisms and limited pre-clinical and
      clinical data, adjunctive immune-stimulatory therapy with interferon-gamma (IFN
      gamma) may represent a promising candidate to improve outcome of invasive fungal
      infections by enhancing host defence mechanisms. METHODS: In this open-label,
      prospective case series, we describe eight patients with invasive Candida and/or
      Aspergillus infections who were treated with recombinant IFN-gamma (rIFN-gamma,
      100 MUg s.c., thrice a week) for 2 weeks in addition to standard antifungal
      therapy. RESULTS: Recombinant IFN-gamma treatment in patients with invasive
      Candida and/or Aspergillus infections partially restored immune function, as
      characterized by an increased HLA-DR expression in those patients with a baseline
      expression below 50%, and an enhanced capacity of leukocytes from treated
      patients to produce proinflammatory cytokines involved in antifungal defence.
      CONCLUSIONS: The present study provides evidence that adjunctive immunotherapy
      with IFN-gamma can restore immune function in fungal sepsis patients, warranting
      future clinical studies to assess its potential clinical benefit. TRIAL
      REGISTRATION: ClinicalTrials.gov--NCT01270490.

PMID- 24669842
TI  - Mycobacterium leprae Hsp65 administration reduces the lifespan of aged high
      antibody producer mice.
AB  - BACKGROUND: Aging process may result in immune modifications that lead to
      disruption of innate and acquired immunity mechanisms that may induce chronic
      degenerative events. The heat shock proteins (Hsp), phylogeneticaly conserved
      among organisms, present as main function the ability of folding and refolding
      proteins, but they also are associated with chronic-degenerative disorders. Here
      were evaluated the role of M. leprae native Hsp65 (WT) and its point-mutated
      (K409A) on survival and anti-DNA and anti-Hsp65 antibody production of aged
      genetically selected mice for high (HIII) and low (LIII) antibody production;
      data from 120- and 270-days old mice (named "adult" or "aged", respectively) were
      compared. RESULTS: WT Hsp65 administration induces reduction in the mean survival
      time of adult and aged female HIII mice, this effect being stronger in aged
      individuals. Surprisingly, the native protein administration increased the
      survival of aged female LIII when compared to K409A and control groups. No
      survival differences were observed in aged male mice after Hsp65 proteins
      inoculation. We observed increase in IgG1 anti-Hsp65 in WT and K409A aged HIII
      female mice groups and no marked changes in the anti-DNA (adult and aged HIII)
      and anti-Hsp65 IgG1 or IgG2a isotypes production in adult HIII female and aged
      male mice. LIII male mice presented increased anti-DNA and anti-Hsp65 IgG2a
      isotype production after WT or K409A injection, and LIII female groups showed no
      alterations. CONCLUSIONS: The results revealed that the WT Hsp65 interferes with
      survival of aged HIII female mice without involvement of a remarkable IgG1 and
      IgG2a anti-DNA and anti-Hsp65 antibodies production. The deleterious effects of
      Hsp65 on survival time in aged HIII female mice could be linked to a gender
      effect and are in agreement with those previously reported in lupus-prone mice.

PMID- 24669843
TI  - Controlled defects in semiconducting carbon nanotubes promote efficient
      generation and luminescence of trions.
AB  - We demonstrate efficient creation of defect-bound trions through chemical doping
      of controlled sp(3) defect sites in semiconducting, single-walled carbon
      nanotubes. These tricarrier quasi-particles luminesce almost as brightly as their
      parent excitons, indicating a remarkably efficient conversion of excitons into
      trions. Substantial populations of trions can be generated at low excitation
      intensities, even months after a sample has been prepared. Photoluminescence
      spectroscopy reveals a trion binding energy as high as 262 meV, which is
      substantially larger than any previously reported values. This discovery may have
      important ramifications not only for studying the basic physics of trions but
      also for the application of these species in fields such as photonics,
      electronics, and bioimaging. 

PMID- 24669844
TI  - Interfacial residues promote an optimal alignment of the catalytic center in
      human soluble guanylate cyclase: heterodimerization is required but not
      sufficient for activity.
AB  - Soluble guanylate cyclase (sGC) plays a central role in the cardiovascular system
      and is a drug target for the treatment of pulmonary hypertension. While the three
      dimensional structure of sGC is unknown, studies suggest that binding of the
      regulatory domain to the catalytic domain maintains sGC in an autoinhibited basal
      state. The activation signal, binding of NO to heme, is thought to be transmitted
      via the regulatory and dimerization domains to the cyclase domain and unleashes
      the full catalytic potential of sGC. Consequently, isolated catalytic domains
      should show catalytic turnover comparable to that of activated sGC. Using X-ray
      crystallography, activity measurements, and native mass spectrometry, we show
      unambiguously that human isolated catalytic domains are much less active than
      basal sGC, while still forming heterodimers. We identified key structural
      elements regulating the dimer interface and propose a novel role for residues
      located in an interfacial flap and a hydrogen bond network as key modulators of
      the orientation of the catalytic subunits. We demonstrate that even in the
      absence of the regulatory domain, additional sGC domains are required to guide
      the appropriate conformation of the catalytic subunits associated with high
      activity. Our data support a novel regulatory mechanism whereby sGC activity is
      tuned by distinct domain interactions that either promote or inhibit catalytic
      activity. These results further our understanding of heterodimerization and
      activation of sGC and open additional drug discovery routes for targeting the NO
      sGC-cGMP pathway via the design of small molecules that promote a productive
      conformation of the catalytic subunits or disrupt inhibitory domain interactions.

PMID- 24669845
TI  - Conducting actigraphy research in children with neurodevelopmental disorders--a
      practical approach.
AB  - The literature has been highly informative for when to use actigraphy and its
      validity in pediatric research. However, minimal literature exists on how to
      perform actigraphy, especially in special populations. We determined whether
      providing actigraphy training to parents and coordinators increased the nights of
      actigraphy data that could be scored. We compared two studies in children with
      autism spectrum disorders, one of which provided a basic level of training in a
      single-site trial and the other of which provided more detailed training to
      parents and coordinators in a multisite trial. There was an increase in scorable
      nights in the multisite trial containing a one-hour structured parent training
      session. Our results support the use of educational tools in clinical trials that
      use actigraphy. 

PMID- 24669846
TI  - Animal models of chronic tympanic membrane perforation: in response to
      plasminogen initiates and potentiates the healing of acute and chronic tympanic
      membrane perforations in mice.
AB  - Tympanic membrane perforations (TMP) are relatively common but are typically not
      treated in their acute stage, as most will heal spontaneously in 7-10 days. Those
      cases which fail to heal within 3 months are called chronic TMP which attract
      surgical intervention (e.g. myringoplasty), typically with a temporalis fascia
      autograft. New materials for the repair of chronic TMP are being developed to
      address deficiencies in the performance of autografts by undergoing evaluation in
      animal models prior to clinical study. However, there is currently a lack of
      ideal chronic TMP animal models available, hindering the development of new
      treatments. Various techniques and animal species have been investigated for the
      creation of chronic TMP with varied success. In the present commentary, we bring
      to the attention of readers the recent report by Shen et al. in Journal of
      Translational Medicine. The study reported the creation of a chronic TMP animal
      model in plasminogen gene deficient mice. However, the short observation time (9,
      19 days), lack of success rate and the scarcity of solid evidence (e.g. otoscopic
      & histologic images) to confirm the chronicity of TMP warrant a more thorough
      discussion. 

PMID- 24669847
TI  - Cophylogenetic interactions between marine viruses and eukaryotic
      picophytoplankton.
AB  - BACKGROUND: Numerous studies have investigated cospeciation (or cophylogeny) in
      various host-symbiont systems, and different patterns were inferred, from strict
      cospeciation where symbiont phylogeny mirrors host phylogeny, to complete absence
      of correspondence between trees. The degree of cospeciation is generally linked
      to the level of host specificity in the symbiont species and the opportunity they
      have to switch hosts. In this study, we investigated cophylogeny for the first
      time in a microalgae-virus association in the open sea, where symbionts are
      believed to be highly host-specific but have wide opportunities to switch hosts.
      We studied prasinovirus-Mamiellales associations using 51 different viral strains
      infecting 22 host strains, selected from the characterisation and experimental
      testing of the specificities of 313 virus strains on 26 host strains. RESULTS:
      All virus strains were restricted to their host genus, and most were species
      specific, but some of them were able to infect different host species within a
      genus. Phylogenetic trees were reconstructed for viruses and their hosts, and
      their congruence was assessed based on these trees and the specificity data using
      different cophylogenetic methods, a topology-based approach, Jane, and a global
      congruence method, ParaFit. We found significant congruence between virus and
      host trees, but with a putatively complex evolutionary history. CONCLUSIONS:
      Mechanisms other than true cospeciation, such as host-switching, might explain a
      part of the data. It has been observed in a previous study on the same taxa that
      the genomic divergence between host pairs is larger than between their viruses.
      It implies that if cospeciation predominates in this algae-virus system, this
      would support the hypothesis that prasinoviruses evolve more slowly than their
      microalgal hosts, whereas host switching would imply that these viruses speciated
      more recently than the divergence of their host genera.

PMID- 24669848
TI  - Association of gingival crevicular fluid cortisol/dehydroepiandrosterone levels
      with periodontal status.
AB  - BACKGROUND: The aim of the present study is to examine whether anxiety and
      depression scale scores change with regard to clinical periodontal status and to
      investigate the association between the levels of stress-related hormones in
      gingival crevicular fluid (GCF) and extent/severity of periodontal disease.
      METHODS: One hundred twenty participants who fulfilled the study inclusion
      criteria were chosen. Patients with chronic periodontitis (CP) and those with
      healthy periodontal tissues/mild gingivitis were included. The clinical
      examinations were performed on the day after the psychologic evaluations which
      included anxiety and depression measurements. GCF sampling was undertaken the
      following day. Commercially available enzyme-linked immunosorbent assay kits were
      used to determine GCF cortisol and dehydroepiandrosterone (DHEA) levels. Study
      groups were assigned as follows: group 1, non-periodontitis; group 2, localized
      CP; and group 3, generalized CP. RESULTS: There were no significant differences
      with respect to age, sex, education, income level, occupation, or smoking history
      among the groups (P >0.05). There were no significant differences between the non
      periodontitis and CP groups for any of the psychosocial scales (P >0.05). Group 3
      had significantly higher mean DHEA scores compared with group 1 (P <0.05);
      however, the median cortisol scores showed no statistically significant
      differences among the three groups (P >0.05). CONCLUSIONS: Anxiety/depression
      scores and GCF cortisol levels did not show any difference with regard to
      clinical periodontal status. However, a significant association was found between
      elevated levels of GCF DHEA and the severity of periodontitis.

PMID- 24669850
TI  - Limited resources lead to newer approach in jaundice therapy.

PMID- 24669849
TI  - Immature articular cartilage and subchondral bone covered by menisci are
      potentially susceptive to mechanical load.
AB  - BACKGROUND: The differences of mechanical and histological properties between
      cartilage covered by menisci and uncovered by menisci may contribute to the
      osteoarthritis after meniscectomy and these differences are not fully understood.
      The purpose of this study is to investigate potential differences in the
      mechanical and histological properties, and in particular the collagen
      architecture, of the superficial cartilage layer and subchondral bone between
      regions covered and uncovered by menisci using immature knee. METHODS:
      Osteochondral plugs were obtained from porcine tibial cartilage that was either
      covered or uncovered by menisci. Investigation of the thickness, mechanical
      properties, histology, and water content of the cartilage as well as micro
      computed tomography analysis of the subchondral bone was performed to compare
      these regions. Collagen architecture was also assessed by using scanning electron
      microscopy. RESULTS: Compared to the cartilage uncovered by menisci, that covered
      by menisci was thinner and showed a higher deformity to compression loading and
      higher water content. In the superficial layer of cartilage in the uncovered
      regions, collagen fibers showed high density, whereas they showed low density in
      covered regions. Furthermore, subchondral bone architecture varied between the 2
      regions, and showed low bone density in covered regions. CONCLUSIONS: Cartilage
      covered by menisci differed from that uncovered in both its mechanical and
      histological properties, especially with regards to the density of the
      superficial collagen layer. These regional differences may be related to local
      mechanical environment in normal condition and indicate that cartilage covered by
      menisci is tightly guarded by menisci from extreme mechanical loading. Our
      results indicate that immature cartilage degeneration and subchondral
      microfracture may occur easily to extreme direct mechanical loading in covered
      region after meniscectomy.

PMID- 24669851
TI  - Stimuli-responsive supramolecular polymers in aqueous solution.
AB  - CONSPECTUS: Aiming to construct various novel supramolecular polymeric structures
      in aqueous solution beyond small supramolecular self-assembly molecules and
      develop functional supramolecular polymeric materials, research interest on
      functional supramolecular polymers has been prevailing in recent years.
      Supramolecular polymers are formed by bridging monomers or components together
      via highly directional noncovalent interactions such as hydrogen bonding,
      hydrophobic interaction, pi-pi interaction, metal-ligand coordination,
      electrostatic interaction, and so forth. They can be easily functionalized by
      employing diverse building components with specific functions besides the
      traditional polymeric properties, a number of which are responsive to such
      external stimuli as pH variance, photoirradiation, chemically or
      electrochemically redox with the controllable conformation or construction
      switching, polymerization building and rebuilding, and function adjustment
      reversibly owing to the reversibility of noncovalent interactions. Supramolecular
      polymers are "soft matters" and can be functionalized with specific properties
      such as morphology adjustment, controllable luminescence, shape memory, self
      healing, and so forth. Supramolecular polymers constructed based on macrocycle
      recognition and interlocked structures represent one typical branch of the
      supramolecular polymer family. Cyclodextrin (CD), cucurbituril (CB), and
      hydrophilic calixarene derivatives are usually employed to construct hydrophilic
      supramolecular polymers in aqueous solution. Stimuli-responsive hydrophilic
      supramolecular polymers, constructed in aqueous solution particularly, can be
      promising candidates for mimicking biocompatible or vital functional materials.
      This Account mainly focuses on the recent stimuli-responsive supramolecular
      polymers based on the host-guest interaction in aqueous solution. We describe the
      hydrophilic supramolecular polymers constructed via hydrophobic effects,
      electrostatic interaction, metal-ligand coordination, and multiple combinations
      of the above noncovalent interactions. The disparate ways to engender stimuli
      responsive supramolecular polymers via the hydrophobic effects of alpha-CD, beta
      CD, and gamma-CD macrocycles are illustrated and discussed. Some recent works on
      CD-based photoresponsive functional supramolecular polymers are summarized. CB
      (especially CB[8]) based supramolecular polymers and their pH-responsive and
      photoresponsive properties are introduced. Hydrophilic calixarene derivative
      (bis(p-sulfonatocalix[4]arene) typically) based supramolecular polymers via
      electrostatic interactions are reviewed, and their redox-responsive
      association/disassociation elaborated in detail. More complicate supramolecular
      polymers based on multiple noncovalent interactions are illustrated including
      hydrophobic effect, metal-ligand coordination, and electrostatic interactions and
      their functional stimuli-responsiveness elaborated as well. Finally, we give
      perspectives on the strength of these diverse noncovalent interactions to form
      supramolecular polymers in aqueous solution, on the advantage, disadvantage,
      efficiency, and reversibility of using certain stimuli in constructing
      supramolecular polymers and prospect the future function improvement of these
      polymers as functional materials.

PMID- 24669852
TI  - Real-world patterns of endocrine therapy for metastatic hormone-receptor-positive
      (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer
      patients in the United States: 2002-2012.
AB  - OBJECTIVE: Clinical guidelines recommend that patients with HR+/HER2- metastatic
      breast cancer (mBC), the most prevalent mBC subtype, receive three lines of
      endocrine therapy (ET) prior to transitioning to chemotherapy (CT) in the absence
      of need for rapid response, symptomatic visceral disease, or suspected endocrine
      resistance. Little is known about real-world ET treatment patterns among HR+/HER2
      mBC patients. RESEARCH DESIGN AND METHODS: Post-menopausal women with HR+/HER2-
      mBC were identified in the MarketScan databases (2002Q3-2012Q2). Patients were
      classified as receiving either ET or CT as their first therapy post-mBC
      diagnosis. Those receiving ET were studied further and stratified into three
      subgroups based on which of the following events occurred first: transition to
      CT, discontinuation of ET (90 days without evidence of ET), or end of data or
      insurance eligibility. MAIN OUTCOME MEASURES: Mean numbers of lines of ET and
      median durations of each line were summarized for the overall sample and
      subgroups. RESULTS: Among a total of 19,120 HR+/HER2- mBC patients, 11,545 (60%)
      initiated an ET; median follow-up time for these patients was 17 months. Seventy
      four percent did not receive a second ET. The average patient received 1.36 lines
      of ET. Among patients with 2+ lines of ET, the duration of each subsequent line
      was significantly shorter than the previous line. RESULTS were similar in all
      subgroups. LIMITATIONS: Clinical characteristics and reasons for treatment
      choices are unavailable in claims data. CONCLUSIONS: Fewer than two thirds of
      patients initiated treatment for HR+/HER2- mBC with ET. Among those who did, most
      received only one line of ET before discontinuation or transition to CT. Patients
      who received multiple lines of ET experienced shorter durations of therapy with
      each line. Real-world treatment with ET falls short of the targets recommended by
      guidelines, representing unmet need for treatment options that improve the
      effectiveness of endocrine therapy.

PMID- 24669854
TI  - Time-resolved IR spectroscopy of 1,3-dicyanophenylcyclopentane-1,3-diyl
      diradicals: CN stretching wavenumber as a vibrational signature of radical
      character.
AB  - CN stretch bands of singlet and triplet cyclopentane-1,3-diyl diradicals (1,3
      di(4-cyanophenyl)-2,2-dimethoxyoctahydropentalene-1,3-diyl and 1,3-di(4
      cyanophenyl)-2,2-dimethyloctahydropentalene-1,3-diyl) were observed by time
      resolved IR spectroscopy. CN stretching wavenumbers of the singlet and triplet
      diradicals were downshifted by 10 and 19 cm(-1) from those of their corresponding
      ring-closed compounds, which are in closed-shell electronic states, respectively.
      The observed downshifts are attributed to the bond-order decrease in the CN bonds
      due to the contribution from a resonance structure that has cumulative double
      bonds (C ? C ? N(*)) at the para-positions of the radical carbons. This resonance
      structure is only possible when the molecules have unpaired electrons; thus, the
      wavenumber downshift can be regarded as an experimental manifestation of the
      radical character of the diradicals. The observed CN stretching wavenumbers
      indicate that the radical character of the singlet diradical is less significant
      than that of the triplet. The smaller radical character is ascribed to the
      contribution from the zwitterionic and pi-single bonding resonance structures in
      the singlet diradical. Unrestricted DFT calculations at the B3LYP level of theory
      with the 6-31G(d) basis set reproduced the small/large relationship between the
      wavenumber downshifts of the singlet and triplet diradicals; however, the shift
      of the singlet diradical was overestimated.

PMID- 24669853
TI  - Gene co-citation networks associated with worker sterility in honey bees.
AB  - BACKGROUND: The evolution of reproductive self-sacrifice is well understood from
      kin theory, yet our understanding of how actual genes influence the expression of
      reproductive altruism is only beginning to take shape. As a model in the
      molecular study of social behaviour, the honey bee Apis mellifera has yielded
      hundreds of genes associated in their expression with differences in reproductive
      status of females, including genes directly associated with sterility, yet there
      has not been an attempt to link these candidates into functional networks that
      explain how workers regulate sterility in the presence of queen pheromone. In
      this study we use available microarray data and a co-citation analysis to
      describe what gene interactions might regulate a worker's response to ovary
      suppressing queen pheromone. RESULTS: We reconstructed a total of nine gene
      networks that vary in size and gene composition, but that are significantly
      enriched for genes of reproductive function. The networks identify, for the first
      time, which candidate microarray genes are of functional importance, as evidenced
      by their degree of connectivity to other genes within each of the inferred
      networks. Our study identifies single genes of interest related to oogenesis,
      including eggless, and further implicates pathways related to insulin,
      ecdysteroid, and dopamine signaling as potentially important to reproductive
      decision making in honey bees. CONCLUSIONS: The networks derived here appear to
      be variable in gene composition, hub gene identity, and the overall interactions
      they describe. One interpretation is that workers use different networks to
      control personal reproduction via ovary activation, perhaps as a function of age
      or environmental circumstance. Alternatively, the multiple networks inferred here
      may represent segments of the larger, single network that remains unknown in its
      entirety. The networks generated here are provisional but do offer a new multi
      gene framework for understanding how honey bees regulate personal reproduction
      within their highly social breeding system.

PMID- 24669855
TI  - Perceived effects of health status on sexual activity in women and men older than
      50 years.
AB  - BACKGROUND: Sexual activity and enjoyment are considered to be important
      components of quality of life (QOL) for adults of all ages. However, limited data
      are available on the effects of health status on sexual activity in women and men
      older than 50 years. Thus, our aim was to explore the perceived effects of health
      status on sexual activity in women and men older than 50 years. METHODS: For this
      purpose we used data from an age and gender matched control study initially
      designed to study QOL in patients with low-energy wrist fracture. We investigated
      patients with wrist fractures older than 50 years (n = 181), as well as age- and
      gender-matched controls (n = 226), who participated in the QOL study. There were
      minimal differences between patients and controls, thus the groups were pooled
      (mean age 67 years (8 SD)). Health-related quality of life (HRQOL) was assessed
      using SF-36 and 15D, and the global quality of life using the Quality of Life
      Scale (QOLS). To assess perceived effects of health status on sexual activity we
      used the question on sexuality from the 15D questionnaires. Group comparisons and
      logistic regression analyses were conducted. RESULTS: The 15D question on
      sexuality was not answered by 25% of the participants. Health status having a
      large negative effect on sexual activity was reported by only 13% of the
      participants. In the multivariate analyses a large negative effect of health
      status on sexual activity was associated with higher age (60-69 years: OR = 5.7,
      95% CI = 1.62-29.2; 70-79 years: OR = 3.60, 95% CI = 0.94-13.9; >=80 years: OR =
      9.04, 95% CI = 1.29-63.4), male gender (OR = 10.8, 95% CI = 3.01-38.9), weight
      (OR = 1.03, 95% CI = 1.00-1.07), low SF-36 PCS score (OR = 0.88, 95% CI = 0.37
      0.93) and a low SF-36 MCS score (OR = 0.92, 95% CI = 0.88-0.96). CONCLUSION: Only
      a small proportion of the participants reported their health status to have a
      large negative effect on sexual activity. Furthermore, health status having a
      negative effect on sexual activity was associated with decreased HRQOL. Insights
      into this important topic may increase our awareness as health care workers and
      help us to address this aspect of QOL in this age group.

PMID- 24669856
TI  - Xanthine derivative KMUP-1 reduces inflammation and hyperalgesia in a bilateral
      chronic constriction injury model by suppressing MAPK and NFkappaB activation.
AB  - Neuropathic pain is characterized by spontaneous pain, hyperalgesia, and
      allodynia. The aim of this study was to investigate whether KMUP-1 (7-[2-[4-(2
      chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) could improve pain
      hypersensitivity and reduce inflammatory mediators, and also explore possible
      mechanisms in the rat sciatic nerve using bilateral chronic constriction injury
      (CCI) to induce neuropathic pain. Sprague-Dawley rats were randomly divided into
      four groups: Sham, Sham+KMUP-1, CCI, and CCI+KMUP-1. KMUP-1 (5 mg/kg/day) was
      injected intraperitoneally starting at day 1 after surgery. Mechanical and
      thermal responses were assessed before surgery and at days 3, 7, and 14 after
      CCI. Sciatic nerves around the injury site were isolated for Western blots and
      enzyme-linked immunosorbent assay to analyze protein and cytokine levels. The
      results show that thermal hyperalgesia and mechanical allodynia were reduced in
      the KMUP-1 treated group as compared to that in the CCI group. Inflammatory
      proteins (COX2, iNOS, and nNOS) and proinflammatory cytokines (TNF-alpha and IL
      1beta) induced by CCI were decreased in the KMUP-1 treated group at day 7 after
      surgery. KMUP-1 also inhibited neuropathic pain-related mechanisms, including p38
      and ERK activation, but not JNK. Furthermore, KMUP-1 blocked IkappaB
      phosphorylation (p-IkappaB) and phospho-nuclear factor kappaB (p-NF-kappaB)
      translocation to nuclei. Double immunofluorescent staining further demonstrated
      that p-IkappaB (an indicator of activated NFkappaB) and p-NFkappaB proteins were
      almost abolished by KMUP-1 in peripheral macrophages and spinal microglia cells
      at day 7 after surgery. On the basis of these findings, we concluded that KMUP-1
      has antiinflammatory and antihyperalgesia properties in CCI-induced neuropathic
      pain via decreases in MAPKs and NF-kappaB activation. 

PMID- 24669857
TI  - Nicotine exaggerates LPS-induced airway hyperreactivity via JNK-mediated up
      regulation of Toll-like receptor 4.
AB  - Tobacco smokers often display increased airway hyperreactivity (AHR) when faced
      with bacterial infections. The present study uses a murine organ-culture model to
      dissect the mechanisms involved in this exaggerated smooth muscle response.
      Nicotine simulates the effects of smoking, and LPS represents bacterial
      infection. Contractile responses of isolated murine tracheal segments were
      analyzed in myographs after organ culture with increasing concentrations of LPS
      and/or nicotine for 4 days with or without specific MAPK inhibitors. Nicotine's
      effect on the expression of cell surface Toll-like receptors (TLRs), MCP-1, COX
      2, and TNF-alpha were examined by real-time PCR. Increased protein expression was
      verified by immunohistochemistry. LPS concentration-dependently increased
      contractile responses to bradykinin and des-Arg(9)-bradykinin. A combination of
      nicotine and low-dose LPS caused powerful synergistic contractions along with
      increased kinin receptor expression. Specific kinin B1 and B2 receptor inhibitors
      blocked this reaction. Nicotine increased mRNA and protein expression of TLR4 and
      -6 in the epithelium and smooth muscle layer, with MCP-1 and COX-2 mRNA
      increasing in parallel. Specific inhibition of JNK attenuated nicotine's effects.
      In conclusion, long-term exposure to nicotine up-regulated the expression of TLR4
      and -6 via a JNK-related pathway, causing an exaggeration of the LPS-induced
      local airway inflammation and increased AHR. This might offer a mechanistic
      explanation to the increased AHR seen in tobacco smokers confronted with
      bacterial infections. 

PMID- 24669858
TI  - Hip adductor activations during run-to-cut manoeuvres in compression shorts:
      implications for return to sport after groin injury.
AB  - Athletes at high risk of groin strains in sports such as hockey and soccer often
      choose to wear shorts with directional compression to aid in prevention of or
      recovery from hip adductor strains. Large, eccentric contractions are known to
      result in or exacerbate strain injuries, but it is unknown if these shorts have a
      beneficial effect on hip adductor muscle activity. In this study, surface
      electromyography (EMG) of the adductor longus and ground reaction force (GRF)
      data were obtained simultaneously on 29 healthy individuals without previous
      history of serious injury while performing unanticipated 45 degrees  run-to-cut
      manoeuvres in a laboratory setting wearing shorts with non-directional
      compression (control, HeatGear, Under Armour, USA) or shorts with directional
      compression (directional, CoreShort PRO, Under Armour, USA), in random order.
      Average adductor activity in the stance leg was significantly lower in the
      directional condition than in the control condition during all parts of stance
      phase (all P < 0.042). From this preliminary analysis, wearing directional
      compression shorts appears to be associated with reduced stance limb hip adductor
      activity. Athletes seeking to reduce demand on the hip adductors as they approach
      full return to activities may benefit from the use of directional compression
      shorts.

PMID- 24669859
TI  - Climate change and dengue: a critical and systematic review of quantitative
      modelling approaches.
AB  - BACKGROUND: Many studies have found associations between climatic conditions and
      dengue transmission. However, there is a debate about the future impacts of
      climate change on dengue transmission. This paper reviewed epidemiological
      evidence on the relationship between climate and dengue with a focus on
      quantitative methods for assessing the potential impacts of climate change on
      global dengue transmission. METHODS: A literature search was conducted in October
      2012, using the electronic databases PubMed, Scopus, ScienceDirect, ProQuest, and
      Web of Science. The search focused on peer-reviewed journal articles published in
      English from January 1991 through October 2012. RESULTS: Sixteen studies met the
      inclusion criteria and most studies showed that the transmission of dengue is
      highly sensitive to climatic conditions, especially temperature, rainfall and
      relative humidity. Studies on the potential impacts of climate change on dengue
      indicate increased climatic suitability for transmission and an expansion of the
      geographic regions at risk during this century. A variety of quantitative
      modelling approaches were used in the studies. Several key methodological issues
      and current knowledge gaps were identified through this review. CONCLUSIONS: It
      is important to assemble spatio-temporal patterns of dengue transmission
      compatible with long-term data on climate and other socio-ecological changes and
      this would advance projections of dengue risks associated with climate change.

PMID- 24669861
TI  - Vaccination directed against the human endogenous retrovirus-K (HERV-K) gag
      protein slows HERV-K gag expressing cell growth in a murine model system.
AB  - BACKGROUND: Human endogenous retroviruses (HERVs) are remnants of ancestral
      infections and chromosomally integrated in all cells of an individual, are
      transmitted only vertically and are defective in viral replication. However
      enhanced expression of HERV-K accompanied by the emergence of anti-HERV-K
      directed immune responses has been observed inter-alia in HIV-infected
      individuals and tumor patients. Therefore HERV-K might serve as a tumor-specific
      antigen or even as a constant target for the development of an HIV vaccine.
      RESULTS: To verify our hypothesis, we tested the immunogenicity of HERV-K Gag by
      using a recombinant vaccinia virus (MVA-HKcon) expressing the HERV-K Gag protein
      and established an animal model to test its vaccination efficacy. Murine renal
      carcinoma cells (Renca) were genetically altered to express E. coli beta
      galactosidase (RLZ cells) and the HERV-K Gag protein (RLZ-HKGag cells).
      Subcutaneous application of RLZ-HKGag cells into syngenic BALB/c mice resulted in
      the formation of local tumors in MVA vaccinated mice. MVA-HKcon vaccination
      reduced the tumor growth. Furthermore, intravenous injection of RLZ-HKGag cells
      led to the formation of pulmonary metastases. Vaccination of tumor-bearing mice
      with MVA-HKcon drastically reduced the number of pulmonary RLZ-HKGag tumor
      nodules compared to vaccination with wild-type MVA. CONCLUSION: The data
      demonstrate that HERV-K Gag is a useful target for vaccine development and might
      offer new treatment opportunities for cancer patients.

PMID- 24669860
TI  - Heat shock protein 90 inhibitors in the treatment of cancer: current status and
      future directions.
AB  - INTRODUCTION: Heat shock protein 90 (HSP90) serves as a critical facilitator for
      oncogene addiction. There has been augmenting enthusiasm in pursuing HSP90 as an
      anticancer strategy. In fact, since the initial serendipitous discovery that
      geldanamycin (GM) inhibits HSP90, the field has rapidly moved from proof-of
      concept clinical studies with GM derivatives to novel second-generation
      inhibitors. AREAS COVERED: The authors highlight the current status of the second
      generation HSP90 inhibitors in clinical development. Herein, the authors note the
      lessons learned from the completed clinical trials of first- and second
      generation inhibitors and describe various assays attempting to serve for a more
      rational implementation of these agents to cancer treatment. Finally, the authors
      discuss the future perspectives for this promising class of agents. EXPERT
      OPINION: The knowledge gained thus far provides perhaps only a glimpse at the
      potential of HSP90 for which there is still much work to be done. Lessons from
      the clinical trials suggest that HSP90 therapy would advance at a faster pace if
      patient selection and tumor pharmacokinetics of these drugs were better
      understood and applied to their clinical development. It is also evident that
      combining HSP90 inhibitors with other potent anticancer therapies holds great
      promise not only due to synergistic antitumor activity but also due to the
      potential of prolonging or preventing the development of drug resistance.

PMID- 24669862
TI  - Three-dimensional nanoporous Fe2O3/Fe3C-graphene heterogeneous thin films for
      lithium-ion batteries.
AB  - Three-dimensional self-organized nanoporous thin films integrated into a
      heterogeneous Fe2O3/Fe3C-graphene structure were fabricated using chemical vapor
      deposition. Few-layer graphene coated on the nanoporous thin film was used as a
      conductive passivation layer, and Fe3C was introduced to improve capacity
      retention and stability of the nanoporous layer. A possible interfacial lithium
      storage effect was anticipated to provide additional charge storage in the
      electrode. These nanoporous layers, when used as an anode in lithium-ion
      batteries, deliver greatly enhanced cyclability and rate capacity compared with
      pristine Fe2O3: a specific capacity of 356 MUAh cm(-2) MUm(-1) (3560 mAh cm(-3)
      or ~1118 mAh g(-1)) obtained at a discharge current density of 50 MUA cm(-2)
      (~0.17 C) with 88% retention after 100 cycles and 165 MUAh cm(-2) MUm(-1) (1650
      mAh cm(-3) or ~518 mAh g(-1)) obtained at a discharge current density of 1000 MUA
      cm(-2) (~6.6 C) for 1000 cycles were achieved. Meanwhile an energy density of 294
      MUWh cm(-2) MUm(-1) (2.94 Wh cm(-3) or ~924 Wh kg(-1)) and power density of 584
      MUW cm(-2) MUm(-1) (5.84 W cm(-3) or ~1834 W kg(-1)) were also obtained, which
      may make these thin film anodes promising as a power supply for micro- or even
      nanosized portable electronic devices. 

PMID- 24669863
TI  - Mitochondria directly donate their membrane to form autophagosomes during a novel
      mechanism of parkin-associated mitophagy.
AB  - BACKGROUND: Autophagy (macroautophagy), a cellular process of "self-eating",
      segregates damaged/aged organelles into vesicles, fuses with lysosomes, and
      enables recycling of the digested materials. The precise origin(s) of the
      autophagosome membrane is unclear and remains a critical but unanswered question.
      Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have
      been proposed as the source of autophagosomal membranes. FINDINGS: Using electron
      microscopy, immunogold labeling techniques, confocal microscopy, and flow
      cytometry we show that mitochondria can directly donate their membrane material
      to form autophagosomes. We expand upon earlier studies to show that mitochondria
      donate their membranes to form autophagosomes during basal and drug-induced
      autophagy. Moreover, electron microscopy and immunogold labeling studies show the
      first physical evidence of mitochondria forming continuous structures with LC3
      labeled autophagosomes. The mitochondria forming these structures also stain
      positive for parkin, indicating that these mitochondrial-formed autophagosomes
      represent a novel mechanism of parkin-associated mitophagy. CONCLUSIONS: With the
      on-going debate regarding autophagosomal membrane origin, this report
      demonstrates that mitochondria can donate membrane materials to form
      autophagosomes. These structures may also represent a novel form of mitophagy
      where the mitochondria contribute to the formation of autophagosomes. This novel
      form of parkin-associated mitophagy may be a more efficient bio-energetic process
      compared with de novo biosynthesis of a new membrane, particularly if the
      membrane is obtained, at least partly, from the organelle being targeted for
      later degradation in the mature autolysosome.

PMID- 24669865
TI  - Expression profiling of glucose transporter 1 (GLUT1) and apoptotic genes (BAX
      and BCL2) in milk enriched mammary epithelial cells (MEC) in riverine buffalo
      during lactation.
AB  - Lactation is an important physiological process in dairy animals. During
      lactation, up to 85% of the body glucose is directed toward the mammary glands
      for milk synthesis. Studies related to lactation physiology are generally carried
      out on mammary biopsies, which may adversely affect animal health. In the present
      study, milk enriched MEC were used to study the expression pattern of GLUT1 and
      apoptotic genes (BAX and BCL2) across different stages of lactation in riverine
      buffalo in relation to milk yield. MEC were enriched from milk using cytokeratin
      8 antibodies coated magnetic beads. Total RNA isolated from enriched MEC showed
      significant correlation (r(2) = 0.92 +/- 0.02) with the milk yield at different
      stages of lactation. GLUT1 expression pattern correlated with the milk yield as
      highest GLUT1 expression (4.68 +/- 0.79) was observed during peak-lactation (90
      days post-parturition), whereas low GLUT1 expression (1.01 +/- 0.1, 15 d; 0.71 +/
      0.03, 30 d) was observed during early lactation. The BAX/BCL2 ratio was high
      (1.02 +/- 0.2, 15 d; 0.94 +/- 0.06, 30 d) during the early phase of lactation,
      indicating high rate of apoptosis, whereas low BAX/BCL2 ratio (0.25 +/- 0.03, 60
      d; 0.42 +/- 0.04, 90 d) was observed during mid-lactation coinciding with the
      increase in RNA concentration and milk yield. Highest BAX/BCL2 ratio (1.41 +/-
      0.3, 120 d; 4.02 +/- 0.6, 240 d) was observed during late lactation i.e., 240
      days, which was also reflected as decline in milk yield and RNA concentration.
      Also, BAX/BCL2 ratio in milk enriched MEC was in accordance with RNA
      concentration in MEC and milk yield at different phases of lactation. Our study
      showed that expression pattern of genes under study (GLUT1, BAX, and BCL2) in
      milk enriched MEC correlated well with important physiological properties such as
      milk yield in buffalo.

PMID- 24669864
TI  - Effects of cytosine methylation on transcription factor binding sites.
AB  - BACKGROUND: DNA methylation in promoters is closely linked to downstream gene
      repression. However, whether DNA methylation is a cause or a consequence of gene
      repression remains an open question. If it is a cause, then DNA methylation may
      affect the affinity of transcription factors (TFs) for their binding sites
      (TFBSs). If it is a consequence, then gene repression caused by chromatin
      modification may be stabilized by DNA methylation. Until now, these two
      possibilities have been supported only by non-systematic evidence and they have
      not been tested on a wide range of TFs. An average promoter methylation is
      usually used in studies, whereas recent results suggested that methylation of
      individual cytosines can also be important. RESULTS: We found that the
      methylation profiles of 16.6% of cytosines and the expression profiles of
      neighboring transcriptional start sites (TSSs) were significantly negatively
      correlated. We called the CpGs corresponding to such cytosines "traffic lights".
      We observed a strong selection against CpG "traffic lights" within TFBSs. The
      negative selection was stronger for transcriptional repressors as compared with
      transcriptional activators or multifunctional TFs as well as for core TFBS
      positions as compared with flanking TFBS positions. CONCLUSIONS: Our results
      indicate that direct and selective methylation of certain TFBS that prevents TF
      binding is restricted to special cases and cannot be considered as a general
      regulatory mechanism of transcription.

PMID- 24669866
TI  - Characterization of hsp70 gene promoter for cis- acting elements in Indian zebu
      cattle of Hariana breed.
AB  - The promoter region of hsp70 gene was characterized for cis-acting elements in
      zebu cattle of Hariana breed. The basal regulatory domain of CAAT box identified
      as CAAT/enhancer binding protein (C/EBP) and CAAT binding transcription factor
      (CTF) binding sites, as well as GC box identified as sp1 binding site, were
      localized in at least two regions in the hsp70 gene promoter. A highly conserved
      heat shock element was found between position -108 to -95, which exactly matched
      at all eight positions with the consensus sequence. These cis-acting elements
      were found to be conserved between Holstein-Friesian and studied zebu breed.

PMID- 24669867
TI  - Effect of Brahman genetic influence on collagen enzymatic crosslinking gene
      expression and meat tenderness.
AB  - The objective of the study was to examine the effect of Brahman genetics on
      collagen enzymatic crosslinking gene expression and meat tenderness. Steers were
      randomly selected to represent a high percentage Brahman genetics (n = 13), Half
      Blood genetics (n = 13), Brangus genetics (n = 13), and a high percentage Angus
      genetics (n = 13). Muscle samples from the Longissimus lumborum muscle were
      collected at weaning and harvest and reverse transcription quantitative PCR
      (qPCR) analysis was conducted to measure the mRNA expression of lysyl oxidase
      (LOX), bone morphogenetic protein 1 (BMP1), and cystatin C (CYS). Steaks from
      subject animals were collected at harvest, aged for 14 d and subjected to
      collagen analysis, Warner-Bratzler Shear Force (WBS) and trained sensory panel
      analysis (tenderness, juiciness, and connective tissue). Data indicated that Half
      Blood and Brahman steers had greater (P<0.05) WBS values and tended to receive
      decreased (P < 0.06) panel tenderness scores than Angus and Brangus steers.
      Panelists tended to detect more connective tissue in Brahman and Half-Blood
      steaks when compared to Angus and Brangus steaks (P < 0.07). Crosslinking gene
      expression data revealed that at weaning Half-Blood steers had more (P < 0.05)
      mRNA expression of CYS and LOX than Angus and Brangus steers. At weaning and
      harvest, all genetic groups had similar mRNA expression of BMP1 (P > 0.10). At
      harvest, Brangus and Angus steers had greater LOX mRNA expression than Brahman
      cattle (P < 0.05). Pearson's correlation coefficients indicated that only weaning
      CYS mRNA expression was correlated to WBS, panel tenderness and connective tissue
      scores (P < 0.05). Expression of LOX was only correlated to these measures at
      harvest, and BMP1 was correlated to these traits at both time periods (P < 0.05).
      These results indicate that collagen crosslinking enzyme activity, as indicated
      by mRNA levels, early in an animal's life may account for some of the variation
      seen in steak tenderness due to Brahman genetic influence.

PMID- 24669868
TI  - Effects of administration of estradiol and progesterone on ovarian stimulation
      response, and in vitro developmental competence of oocytes in CIDR-treated
      calves.
AB  - The present study was conducted to investigate the effects of administering
      estradiol (estradiol-17beta, 2.5 mg) plus progesterone (P4, 50 mg) as a part of a
      controlled internal drug release (CIDR)-based superovulation protocol on ovarian
      follicles development, and oocyte recovery as well as on in vitro development in
      prepubertal calves after follicle stimulating hormone (FSH) stimulation. Calves
      in the treatment group exhibited significantly decreased (P < 0.05) numbers of
      both small and large antral follicles compared to the control group A and B (<3
      mm in diameter [small], 3.4 versus 12.8, 11.6; > 7 mm in diameter [large], 0
      versus 7.6, 7.2). The treated animals also exhibited an increased (P < 0.05)
      proportion of usable oocytes from the total oocytes recovered compared with those
      of the control group A and B (77% versus 50.2%, 47.8%). Moreover, the rate of
      cleavage and the percentage of blastocysts displayed an increased trend in the
      treatment group compared to controls A and B (59.2% versus 50.5%, 50.8%; 15%
      versus 12.4%, 11.6%, respectively). In conclusion, the application of estradiol
      17beta plus P4 at CIDR insertion prior to FSH stimulation affected ovarian
      follicles development and exerted a beneficial effect on the in vitro development
      of calf oocytes.

PMID- 24669869
TI  - Molecular characterization and expression profile of partial TLR4 gene in
      association to mastitis in crossbred cattle.
AB  - Crossbred cattle are more prone to mastitis in comparison to indigenous cattle.
      Toll-like receptor 4 (TLR4) recognizes pathogen ligands, for example,
      lipopolysaccharide (LPS) endotoxin from Escherichia coli and mediates signaling
      to initiate innate and adaptive immune responses. Mutations in TLR4 can
      compromise the host immune response to certain pathogens, so it may be a
      potential candidate for marker assisted selection to enhance mastitis resistance
      in dairy cattle. Hence, in this study role of bovine TLR4 gene in mastitis
      resistance was investigated by association as well as expression profiling
      analysis in crossbred cattle. The animals were divided into mastitis affected and
      unaffected groups on the basis of history of animals and California Mastitis Test
      (CMT). PCR-SSCP and Sequence analysis revealed three genotypes of coreceptor
      binding region 1 (CRBR1) fragment of TLR4 gene namely AA, AB, and BB in both
      groups of cattle. The logistic regression model did not show any significant
      effect of these genotypes on the occurrence of clinical mastitis. Moreover, in
      vitro challenge of peripheral blood mononuclear cells (PBMCs) with LPS failed to
      show any association of the genotypes with TLR4 gene expression. In a nutshell,
      in the present study enough evidence was not found for association of the SNP
      variants of CRBR1 fragment of TLR4 gene with mastitis susceptibility in crossbred
      cattle. 

PMID- 24669870
TI  - Stage specific expression of ATP-binding cassette and solute carrier superfamily
      of transporter genes in mammary gland of riverine buffalo (Bubalus bubalis).
AB  - In the present study, expression level of various ATP-binding cassette (ABC)
      viz., ABCA1, ABCA7, ABCG1, ABCG2, and ABCG5; associated transcription factors
      viz., SREBF1, LXRalpha (NR1H3), PPARA, and Solute Carriers (SLC); or Glucose
      transporters (GLUT) viz., SLC2A1(GLUT1), SLC2A4 (GLUT4), SLC2A8 (GLUT8), and
      SLC2A12 (GLUT12) superfamily of transporters were compared across physiological
      stages of buffalo mammary gland. The relative expression of ABCA1, and ABCG1 was
      significantly (p < 0.05) higher in mammary gland of heifer followed by involution
      and lactation stages. Similarly, ABCA7 gene expression was highest in heifer
      mammary gland followed by lactation and involution stages. ABCG2 gene expression
      was significantly (p < 0.05) high in lactating mammary gland in comparison to
      involution and heifer stages. On the other hand, ABCG5 gene expression was
      highest in involuting mammary gland followed by lactation and involution stages.
      Additionally, the expression of LXRalpha SREBF1, and PPARA which are known to
      regulate some of the ABC tranporters were also analyzed. The expression of
      LXRalpha gene was high in involuting as compared to lactating mammary gland. In
      contrast, SREBF1 and PPARA expression was significantly (p < 0.05) high in
      lactating mammary gland. Among the several SLC transporters studied, SLC2A1,
      SLC2A4, and SLC2A8 showed significant (p < 0.05) higher expression during
      lactation stage, whereas SLC2A12 expression was greater during heifer stage
      suggesting SLC2A1, SLC2A4, and SLC2A8 to be the major transporters associated
      with glucose uptake in buffalo mammary gland. The expression profile of
      (lactoferrin) LTF, known to be expressed at high level in mammary gland during
      involution was also studied. As expected, its expression was significantly (p <
      0.05) higher during involution in comparison to lactating mammary gland.in
      buffaloes as well. The inclusion of LTF as a control gene further provided the
      confidence in the buffalo mammary gland expression data generated in the present
      study. This study thus helped to provide information about the distinct
      expression pattern of various transporters and their regulators in buffalo
      mammary gland during different physiological states.

PMID- 24669871
TI  - Microsatellite based phylogeny and bottleneck studies of Iranian indigenous goat
      populations.
AB  - Genetic analyses, structure, and bottlenecks were examined in six populations of
      Iranian indigenous goat using 13 microsatellite loci. The overall heterozygosity,
      polymorphism information content (PIC), and Shannon index values were 0.80, 0.74,
      and 2.14, respectively, indicating high genetic diversity. Both a phylogenetic
      tree and factorial correspondence analysis grouped the populations into two major
      clusters. Signatures for bottleneck events in the populations were examined by
      two methods, which suggested that bottlenecks had occurred in two Tali and
      Markhoz populations, whereas other populations (Raeini, Korki jonobe Khorasan,
      Lori, and Najdi) showed no signature of a genetic bottleneck in the recent past.
      The results showed that Iranian goats have high genetic diversity and may be of
      value to alternative breeding and conservation programs. 

PMID- 24669873
TI  - Interaction between prion protein and Abeta amyloid fibrils revisited.
AB  - Recent studies indicate that the pathogenesis of Alzheimer disease may be related
      to the interaction between prion protein (PrP) and certain oligomeric species of
      Abeta peptide. However, the mechanism of this interaction remains unclear and
      controversial. Here we provide direct experimental evidence that, in addition to
      previously demonstrated binding to Abeta oligomers, PrP also interacts with
      mature Abeta fibrils. However, contrary to the recent claim that PrP causes
      fragmentation of Abeta fibrils into oligomeric species, no evidence for such a
      disassembly could be detected in the present study. In contrast, our data
      indicate that the addition of PrP to preformed Abeta fibrils results in a lateral
      association of individual fibrils into larger bundles. These findings have
      potentially important implications for understanding the mechanism by which PrP
      might impact Abeta toxicity as well as for the emerging efforts to use PrP
      derived compounds as inhibitors of Abeta-induced neurodegeneration.

PMID- 24669872
TI  - Inflammatory biomarkers in serum in subjects with and without work related
      neck/shoulder complaints.
AB  - BACKGROUND: Although it has recently been recognised that inflammation is
      important in the development of work-related musculoskeletal disorders (MSDs),
      the exact pathophysiological pathways are unknown. METHODS: We investigated serum
      concentrations of inflammatory cytokines in 35 female supermarket cashiers with
      repetitive work tasks and work related neck/shoulder complaints, compared with
      those from 25 women without MSDs (6 supermarket cashiers and 19 middle-school
      teachers or faculty staff). None of the subjects were pregnant or lactating, and
      showed no signs of rheumatoid arthritis, systemic lupus erythematosus, cancer,
      diabetes, coronary artery disease or inadequately controlled hypertension. Serum
      levels of IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, IL-12, MCP-1, MIP-1alpha, MIP
      1beta, TNF-alpha, GM-CSF, CTGF and CRP were analysed. RESULTS: The women with
      pain related to MSD had higher serum concentrations of MIP-1beta (median, 25th
      75th percentile: 90.0 pg/mL, 62.5-110 vs. 73.1 pg/mL, 54.6-88.3; p = 0.018), IL
      12 (0.26 pg/mL, 0.26-0.26 vs. 0.26 pg/mL, 0.26-0.26; p = 0.047) and CRP (0.5
      mg/L, 0.5-1.6 vs. 0.5 mg/L, 0.5-0.5; p = 0.003), than control subjects. Levels of
      MIP-1alpha, MIP-1beta and CRP were correlated with the reported intensity of
      neck/shoulder pain (r = 0.29, p = 0.03 for MIP-1alpha; r = 0.29, p = 0.02 for MIP
      1beta and r = 0.43, p = 0.001 for CRP). No statistically significant differences
      in serum levels were found for the remaining cytokines. CONCLUSIONS: Otherwise
      healthy females with ongoing work-related neck/shoulder pain showed higher serum
      concentrations of MIP-1beta, IL-12 and CRP than controls, and the levels of MIP
      1alpha, MIP-1beta and CRP were correlated to pain intensity. These results
      support previous findings that inflammatory processes play a part in work related
      MSDs.

PMID- 24669874
TI  - Single-site community consultation for emergency research in a community hospital
      setting.
AB  - OBJECTIVES: The purpose of this study was to evaluate community member feedback
      from community consultation and public disclosure activities performed for a
      clinical investigation involving a device designed to treat traumatic brain
      injury in prehospital contexts. The clinical investigation of that device was to
      be performed under the federal regulations providing an exception from
      prospective informed consent requirements in emergency settings. Secondarily, we
      sought to assess the community consultation process by measuring the levels of
      outreach provided by the different communication methods used in these
      activities, with special attention to the effectiveness of social media for
      community outreach. METHODS AND SETTING: The medical device investigation
      consists of a single-site pilot study based at a 345-bed community hospital in
      east central Illinois, which also serves as the area's only level I trauma
      center. Investigators, in collaboration with the local institutional review
      board, fulfilled community consultation and public disclosure requirements
      through four public town hall meetings, seven targeted focus groups, targeted
      mailings to 884 community leaders and researchers, a press conference and press
      release, internal and external websites, and multiple postings to the hospital's
      Facebook and Twitter accounts. Community members provided feedback by completing
      paper or electronic comment cards. RESULTS: A total of 428 community members
      attended the four town hall meetings and seven focus group sessions. Attendance
      at each meeting ranged from 4 to 20 attendees for the town hall meetings and 8 to
      140 attendees for the focus groups. The investigation's external website received
      626 unique visitors and the intranet website received 528 unique visits. Social
      media postings on Facebook and Twitter received six comments and eight "likes" to
      indicate that an individual read the posting. In total, attendees completed 175
      comment cards to provide their feedback. Community member attitudes regarding the
      research were very positive, with 173 (98.8%) comment card respondents viewing
      the research as beneficial and 162 (92.6%) indicating that they would allow
      themselves or their family members to participate in the research. CONCLUSIONS:
      The internal and external websites provided the most effective means for sharing
      research-related information to community members. While cost-effective, social
      media outreach was very limited and did not foster communication with community
      members.

PMID- 24669875
TI  - A comparison of total versus partial omentectomy for advanced gastric cancer in
      laparoscopic gastrectomy.
AB  - BACKGROUND: Minimally invasive surgery has been slowly introduced into the field
      of advanced gastric cancer (AGC) surgery. However, the appropriate extent of
      omentectomy during laparoscopic gastrectomy for AGC is unknown. METHODS: From
      July 2004 to December 2011, 146 patients with serosa-negative advanced gastric
      cancer were divided into the total omentectomy group (TO group, n = 80) and the
      partial omentectomy group (PO group, n = 66). The clinicopathologic
      characteristics, surgical outcomes, recurrence pattern and survival were
      analyzed. RESULTS: There were no significant differences in the clinicopathologic
      features between the two groups, except for depth of invasion; more T3
      (subserosal invasion) cases (65%) were included in total omentectomy group (P =
      0.011). The mean time for PO was significantly shorter (35.1 +/- 13.0 min) than
      TO (50.9 +/- 15.3 min) (P %0.001), and there were two omentectomy-related
      complications in the TO group: spleen and mesocolon injuries. Recurrence occurred
      in 14 (17.5%) and 5 (7.6%) cases in the TO and PO group, respectively (P =
      0.054). Disease-free survival (TO versus PO: 81.5% versus 89.3%, P = 0.420) and
      disease-specific survival (TO versus PO: 89% versus 94.7%) were not significantly
      different between the two groups. In the case-matched analysis using propensity
      score matching, there was no difference in disease-free survival (TO versus PO:
      83.3% versus 90.5%, P = 0.442). CONCLUSIONS: Partial omentectomy might be an
      oncologically safe procedure during laparoscopic gastrectomy for serosa-negative
      advanced gastric cancer, similar to early gastric cancer.

PMID- 24669877
TI  - Overview of the Affordable Care Act's impact on military and veteran mental
      health services: nine implications for significant improvements in care.
AB  - On March 23, 2010, President Barack Obama signed the Affordable Care Act (ACA)
      into law. Implications of the ACA on mental health care for 9.7 million military
      active-duty, reserve, and family members and 22.2 million veterans, as well as
      1.3 uninsured veterans, is reviewed in light of a major crisis. The authors trace
      historical roots of the ACA to the World War II generation and efforts to
      transform the mental health care system by implementing hard-won war trauma
      lessons. The authors posit 9 principles reflected in the ACA that represent
      unfulfilled generational war trauma lessons and potential transformation of the
      military and national mental health care systems. 

PMID- 24669876
TI  - Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes
      mellitus: a double blind, randomized comparison with pioglitazone.
AB  - OBJECTIVE: To compare efficacy and safety of hydroxychloroquine with pioglitazone
      in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This double
      blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c >=7.5%
      and <=11.5%), post 3 months' treatment with glimepiride/gliclazide and metformin,
      to additionally receive hydroxychloroquine 400 mg/day (n = 135) or pioglitazone
      15 mg/day (n = 132) for 24 weeks. Efficacy was assessed by changes in HbA1c,
      fasting (FBG) and post-prandial (PPG) blood glucose at Week 12 and Week 24.
      RESULTS: At Week 12 and Week 24, HbA1c, FBG and PPG significantly reduced from
      baseline in both groups. Mean reduction in glycemic parameters at Week 12 (HbA1c:
      -0.56% vs -0.72%, p = 0.394; FBG: -0.99 mmol/L vs -1.05 mmol/L, p = 0.878; PPG: 
      1.93 mmol/L vs -1.52 mmol/L, p = 0.423) and Week 24 (HbA1c: -0.87% vs -0.90%, p =
      0.909; FBG: -0.79 mmol/L vs -1.02 mmol/L, p = 0.648; PPG: -1.77 mmol/L vs -1.36
      mmol/L, p = 0.415) was not significantly different between the hydroxychloroquine
      and pioglitazone groups. Change in total cholesterol (TC) and LDL-C was
      significant in favor of hydroxychloroquine (TC: -0.37 mmol/L vs 0.03 mmol/L, p =
      0.002; LDL-C: -0.23 mmol/L vs 0.09 mmol/L, p = 0.003). Triglycerides
      significantly reduced in both groups at Week 24. Mean HDL-C remained unchanged.
      Study treatments were well tolerated. CONCLUSION: With favorable effects on
      glycemic parameters and lipids, hydroxychloroquine may emerge as well tolerated
      therapeutic option for T2DM. LIMITATIONS: The sample size for this study was
      small. However, based on the encouraging results of this proof-of-concept study,
      longer duration studies in larger population can be conducted to further confirm
      these findings. TRIAL REGISTRATION DETAILS: Clinical Trial Registry-India URL:
      http://ctri.nic.in, Registration Number: CTRI/2009/091/001036.

PMID- 24669878
TI  - Novel two-stage surgical treatment for Cantrell syndrome complicated by severe
      pulmonary hypertension: a case report.
AB  - INTRODUCTION: Cantrell syndrome is a rare syndrome of congenital defects, which
      can be complicated by severe pulmonary hypertension and left ventricular
      diverticulum; it has proved difficult to treat in clinical practice. CASE
      PRESENTATION: A 6-month-old Han Chinese baby girl weighing 3.5 kg was diagnosed,
      using ultrasonography and radiography, as having Cantrell syndrome complicated by
      severe pulmonary hypertension. For safety, we divided management into two stages.
      For the first stage, we dealt with the left ventricular diverticulum and
      pulmonary hypertension. Three months later, we performed diorthosis for an
      intracardiac malformation. CONCLUSIONS: Cantrell syndrome with pulmonary
      hypertension may respond well to this novel two-stage operation, which needs more
      verification via clinical practice.

PMID- 24669879
TI  - Exposure to cigarette smoke during pregnancy causes redox imbalance and
      histological damage in lung tissue of neonatal mice.
AB  - Smoking during pregnancy is directly associated with numerous serious conditions,
      such as premature birth, low birth weight, and perinatal mortality. We
      quantitatively evaluated histological inflammatory alterations, oxidative damage
      by lipid peroxidation, the activity of the antioxidant enzymes superoxide
      dismutase (SOD) and catalase (CAT) in the lungs of mice exposed to cigarette
      smoke during pregnancy. Eight female and four male mice were mated for five days.
      Pregnant female mice were randomly allocated to the control group or to the
      cigarette smoke group (n = 8) in which they were exposed to 12 cigarettes per day
      in an exposure chamber, three times a day for 21 days. The control group (CG; n =
      8) was kept in the exposure chamber for the same duration, but without exposure
      to cigarette smoke. Six newborn mice from both groups were weighed 24 hours after
      birth and then euthanized. Lung tissue was collected and subjected to
      histomorphometric and biochemical analyses. The cigarette smoke group showed a
      significant reduction in snout-vent length compared to the control group.
      Histomorphometric analysis indicated increased alveolar septal thickness and a
      larger alveolar lumen in mice exposed to cigarette smoke than in mice in the
      control group. We observed increased alveolar inflammatory infiltrate, decreased
      SOD activity, and significantly higher oxidative damage in the cigarette smoke
      group. Our data indicate that cigarette smoke exposure during pregnancy decreases
      body length at birth, changes lung tissue, and causes redox imbalance and
      histological damage in newborn mice.

PMID- 24669880
TI  - Improving the TAMI for use with athletes.
AB  - Athletes have been shown to have greater movement imagery abilities than non
      athletes. However, since these differences were observed using questionnaires
      where participants subjectively judged the vividness of performing imagined
      movements, it is possible that responses could be biased by other factors such as
      social desirability. One possible solution is to use an objective test, such as
      the Test of Ability in Movement Imagery (TAMI; Madan, C. R., & Singhal, A.
      (2013). Introducing TAMI: An objective test of ability in movement imagery.
      Journal of Motor Behavior, 45, 153-166.). Unfortunately, young adults perform
      relatively well on the TAMI, leaving little room for statistical sensitivity in
      observing higher scores. Here we propose an alternate scoring method for the TAMI
      that resolves this limitation by weighing items according to their difficulty. We
      apply this scoring method to existing data and show that this improves the TAMI's
      selectivity to measuring ability in movement imagery, rather than related imagery
      processes. Thus, we have successfully improved the TAMI to be more suited for use
      with athletic populations.

PMID- 24669881
TI  - Malaria prevalence, anemia and baseline intervention coverage prior to mass net
      distributions in Abia and Plateau States, Nigeria.
AB  - BACKGROUND: Nigeria suffers the world's largest malaria burden, with
      approximately 51 million cases and 207,000 deaths annually. As part of the
      country's aim to reduce by 50% malaria-related morbidity and mortality by 2013,
      it embarked on mass distribution of free long-lasting insecticidal nets (LLINs).
      METHODS: Prior to net distribution campaigns in Abia and Plateau States, Nigeria,
      a modified malaria indicator survey was conducted in September 2010 to determine
      baseline state-level estimates of Plasmodium prevalence, childhood anemia, indoor
      residual spraying (IRS) coverage and bednet ownership and utilization. RESULTS:
      Overall age-adjusted prevalence of Plasmodium infection by microscopy was similar
      between Abia (36.1%, 95% CI: 32.3%-40.1%; n = 2,936) and Plateau (36.6%, 95% CI:
      31.3%-42.3%; n = 4,209), with prevalence highest among children 5-9 years. P.
      malariae accounted for 32.0% of infections in Abia, but only 1.4% of infections
      in Plateau. More than half of children <=10 years were anemic, with anemia
      significantly higher in Abia (76.9%, 95% CI: 72.1%-81.0%) versus Plateau (57.1%,
      95% CI: 50.6%-63.4%). Less than 1% of households in Abia (n = 1,305) or Plateau
      (n = 1,335) received IRS in the 12 months prior to survey. Household ownership of
      at least one bednet of any type was 10.1% (95% CI: 7.5%-13.4%) in Abia and 35.1%
      (95% CI: 29.2%-41.5%) in Plateau. Ownership of two or more bednets was 2.1% (95%
      CI: 1.2%-3.7%) in Abia and 14.5% (95% CI: 10.2%-20.3%) in Plateau. Overall
      reported net use the night before the survey among all individuals, children <5
      years, and pregnant women was 3.4%, 6.0% and 5.7%, respectively in Abia and
      14.7%, 19.1% and 21.0%, respectively in Plateau. Among households owning nets,
      34.4% of children <5 years and 31.6% of pregnant women in Abia used a net,
      compared to 52.6% of children and 62.7% of pregnant women in Plateau.
      CONCLUSIONS: These results reveal high Plasmodium prevalence and childhood anemia
      in both states, low baseline coverage of IRS and LLINs, and sub-optimal net use
      especially among age groups with highest observed malaria burden.

PMID- 24669882
TI  - Miglitol increases energy expenditure by upregulating uncoupling protein 1 of
      brown adipose tissue and reduces obesity in dietary-induced obese mice.
AB  - BACKGROUND: Miglitol is an oral anti-diabetic drug that acts by inhibiting
      carbohydrate absorption in the small intestine. Recent studies have shown that
      miglitol reduces obesity in humans and rodents. However, its mechanisms have
      remained unclear. The purpose of this study was to determine whether miglitol
      generates heat by activating uncoupling protein 1 (UCP1), an enzyme involved in
      thermogenesis, in brown adipose tissue (BAT) in mice. METHODS: Four-week-old male
      C57BL/6 J mice were fed a high-fat diet alone (HF) or a high fat diet plus
      miglitol (HFM). Oxygen consumption (VO2) was used to estimate metabolic rate. A
      thermal imaging camera was used to quantify heat generation from interscapular
      brown adipose tissue. We analyzed the protein and gene expressions of UCP1 and
      the expressions of four proteins related to beta3-adrenergic signaling in the
      pathway activating UCP1 (protein kinase A (PKA), hormone-sensitive lipase (HSL),
      p38 alpha mitogen-activated protein kinase (p38alphaMAPK) and peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha)). RESULTS:
      At 8 weeks, body weight, epididymal and subcutaneous white adipose tissue and the
      HOMA-R value of the HFM mice were significantly less than those of the HF mice.
      Food intake was not different between the HF and HFM mice. VO2 and BAT
      temperature were significantly higher in the HFM mice. Miglitol significantly
      enhanced the gene and protein expressions of UCP1 and the expressions of proteins
      related to beta3-adrenergic signaling. CONCLUSIONS: Miglitol's anti-obesity
      effect was attributed to increased energy expenditure by upregulating UCP1 in BAT
      (i.e., by thermogenesis) and to enhancement of beta3-adrenergic signaling in BAT.

PMID- 24669884
TI  - Phase-pure FeSe(x) (x = 1, 2) nanoparticles with one- and two-photon
      luminescence.
AB  - Iron chalcogenides hold considerable promise for energy conversion and biomedical
      applications. Realization of this promise has been hindered by the lack of
      control over the crystallinity and nanoscale organization of iron chalcogenide
      films. High-quality nanoparticles (NPs) from these semiconductors will afford
      further studies of photophysical processes in them. Phase-pure NPs from these
      semiconductors can also serve as building blocks for mesoscale iron chalcogenide
      assemblies. Herein we report a synthetic method for FeSe(x) (x = 1, 2) NPs with a
      diameter of ca. 30 nm that satisfy these needs. The high crystallinity of the
      individual NPs was confirmed by transmission electron microscopy (TEM) and energy
      dispersive X-ray analysis. TEM tomography images suggest pucklike NP shapes that
      can be rationalized by bond relaxation at the NP edges, as demonstrated in large
      scale atomic models. The prepared FeSe(x) NPs display strong photoluminescence
      with a quantum yield of 20%, which was previously unattainable for iron
      chalcogenides. Moreover, they also show strong off-resonant luminescence due to
      two-photon absorption, which should be valuable for biological applications.

PMID- 24669883
TI  - Critical role of vascular endothelial growth factor secreted by mesenchymal stem
      cells in hyperoxic lung injury.
AB  - Intratracheal transplantation of human umbilical cord blood (UCB)-derived
      mesenchymal stem cells (MSCs) protects against neonatal hyperoxic lung injury by
      a paracrine rather than a regenerative mechanism. However, the role of paracrine
      factors produced by the MSCs, such as vascular endothelial growth factor (VEGF),
      has not been delineated. This study examined whether VEGF secreted by MSCs plays
      a pivotal role in protecting against neonatal hyperoxic lung injury. VEGF was
      knocked down in human UCB-derived MSCs by transfection with small interfering RNA
      specific for human VEGF. The in vitro effects of MSCs with or without VEGF
      knockdown or neutralizing antibody were evaluated in a rat lung epithelial (L2)
      cell line challenged with H2O2. To confirm these results in vivo, newborn Sprague
      Dawley rats were exposed to hyperoxia (90% O2) for 14 days. MSCs (1 * 10(5)
      cells) with or without VEGF knockdown were administered intratracheally at
      postnatal Day 5. Lungs were serially harvested for biochemical and histologic
      analyses. VEGF knockdown and antibody abolished the in vitro benefits of MSCs on
      H2O2-induced cell death and the up-regulation of inflammatory cytokines in L2
      cells. VEGF knockdown also abolished the in vivo protective effects of MSCs in
      hyperoxic lung injury, such as the attenuation of impaired alveolarization and
      angiogenesis, reduction in the number of terminal deoxynucleotidyl transferase
      dUTP nick end labeling-positive and ED-1-positive cells, and down-regulation of
      proinflammatory cytokine levels. Our data indicate that VEGF secreted by
      transplanted MSCs is one of the critical paracrine factors that play seminal
      roles in attenuating hyperoxic lung injuries in neonatal rats. 

PMID- 24669885
TI  - Quantum dot solar cells: hole transfer as a limiting factor in boosting the
      photoconversion efficiency.
AB  - Semiconductor nanostructures are attractive for designing low-cost solar cells
      with tunable photoresponse. The recent advances in size- and shape-selective
      synthesis have enabled the design of quantum dot solar cells with photoconversion
      efficiencies greater than 5%. To make them competitive with other existing thin
      film or polycrystalline photovoltaic technologies, it is important to overcome
      kinetic barriers for charge transfer at semiconductor interfaces. This feature
      article focuses on the limitations imposed by slow hole transfer in improving
      solar cell performance and its role in the stability of metal chalcogenide solar
      cells. Strategies to improve the rate of hole transfer through surface-modified
      redox relays offer new opportunities to overcome the hole-transfer limitation.
      The mechanistic and kinetic aspects of hole transfer in quantum dot solar cells
      (QDSCs), nanowire solar cells (NWSCs), and extremely thin absorber (ETA) solar
      cells are discussed. 

PMID- 24669886
TI  - Impact of Environmental Stresses on Orange Oil-in-Water Emulsions Stabilized by
      Sucrose Monopalmitate and Lysolecithin.
AB  - The food and beverage industry is trying to replace synthetic functional
      ingredients with more "label-friendly" ingredients in many commercial products.
      This study therefore examined the influence of environmental stresses on the
      stability of emulsions stabilized by a combination of lysolecithin and sucrose
      monopalmitate (SMP). Orange oil-in-water emulsions (5% (w/w) oil) stabilized by
      SMP (1%) and lysolecithin (0-0.5%) were prepared using high-pressure
      homogenization (pH 3). In the absence of lysolecithin, all emulsions were highly
      unstable to droplet aggregation, which was attributed to low droplet charge (weak
      electrostatic repulsion) and small SMP headgroup size (weak steric repulsion).
      Incorporation of 0.1-0.5% lysolecithin into the emulsions greatly improved their
      stability to droplet aggregation, which was mainly attributed to the increase in
      negative charge on the droplets (strong electrostatic repulsion). The addition of
      high levels of salt (NaCl) to the emulsions promoted droplet aggregation and
      creaming. Emulsions containing 0.5% lysolecithin were stable to heating (30-90 
      degrees C) in the absence of salt, but exhibited droplet aggregation and creaming
      when held at high (>50  degrees C) temperatures in the presence of 300 mM salt.
      This study has implications for the development of emulsion-based delivery
      systems for use in food and beverage products.

PMID- 24669887
TI  - Efficient synthesis of functionalized benzo[b][1,8]naphthyridine derivatives via
      three-component reaction catalyzed by L-proline.
AB  - A facile and efficient one-pot procedure for the preparation of functionalized
      benzo[b][1,8]naphthyridine derivatives by three-component reaction of 2
      chloroquinoline-3-carbaldehyde, 1,3-dicarbonyl compounds, and enaminones
      catalyzed by l-proline is described. This new protocol has the advantages of
      environmental friendliness, good yields, and convenient operation. 

PMID- 24669888
TI  - Design, synthesis, and biological evaluation of novel pyridine-bridged analogues
      of combretastatin-A4 as anticancer agents.
AB  - A series of novel pyridine-bridged analogues of combretastatin-A4 (CA-4) were
      designed and synthesized. As expected, the 4-atom linker configuration retained
      little cytotoxicities in the compounds 2e, 3e, 3g, and 4i. Activities of the
      analogues with 3-atom linker varied widely depending on the phenyl ring
      substitutions, and the 3-atom linker containing nitrogen represents the more
      favorable linker structure. Among them, three analogues (4h, 4s, and 4t) potently
      inhibited cell survival and growth, arrested cell cycle, and blocked angiogenesis
      and vasculature formation in vivo in ways comparable to CA-4. The superposition
      of 4h and 4s in the colchicine-binding pocket of tubulin shows the binding
      posture of CA-4, 4h, and 4s are similar, as confirmed by the competitive binding
      assay where the ability of the ligands to replace tubulin-bound colchicine was
      measured. The binding data are consistent with the observed biological activities
      in antiproliferation and suppression of angiogenesis but are not predictive of
      their antitubulin polymerization activities. 

PMID- 24669890
TI  - [Pharmacokinetic monitoring as a new tool to individualize anti-TNF therapy].

PMID- 24669889
TI  - Advantages of a combined rheumatoid arthritis magnetic resonance imaging score
      (RAMRIS) for hand and feet: does the RAMRIS of the hand alone underestimate
      disease activity and progression?
AB  - BACKGROUND: To evaluate a combined rheumatoid arthritis magnetic resonance
      imaging score (RAMRIS) for hand and foot (HaF-score) in rheumatoid arthritis
      (RA). METHODS: Magnetic resonance imaging (MRI, 0.2 Tesla) of the dominant hand
      and foot of 26 ACPA positive RA patients before and 6 months after initiation of
      methotrexate was obtained. RAMRIS of the hand was complemented by corresponding
      scoring of the foot (MTP I-V; HaF-score). Disease Activity Score 28 (DAS28) and a
      tender and swollen joint count (JC) of the joints scored in MRI were recorded.
      Changes in these scores (Delta) were assessed. RESULTS: DeltaHaF-score correlated
      significantly with DeltaDAS28 (r = 0.820, 95%-CI 0.633-0.916). Correlations to
      DeltaDAS28 were best for changes in the synovitis subscore (0.648) and bone
      marrow edema (0.703). Correlations to DeltaDAS28 were significantly better for of
      the DeltaHaF-score than DeltaRAMRIS (0.499, 0.139-0.743, p = 0.0368).All patients
      with at least moderate response (EULAR criteria, n = 11) had continuing disease
      activity on MRI, including five cases with new erosions, three of them at the
      feet. Improvements of the hand JC or foot JC were seen in 16 and 15 cases,
      respectively. However, MRI of the hand or feet improved in only 10 and 9 cases,
      respectively. No patient fulfilled SDAI remission criteria. CONCLUSIONS: The HaF
      score identifies patients with continuing disease activity despite clinical
      response that would have been missed by consideration of the traditional RAMRIS
      or the DAS28 alone. Response as opposed to remission may be an insufficient goal
      in RA as all patients showed continuing disease activity, especially at the feet.

PMID- 24669891
TI  - [Recommendations for the use of social networks by hospital pharmacists (12
      advises that one should consider before jumping into the network)].
AB  - -

PMID- 24669892
TI  - [Status of the structure, process and outcoms of pharmaceutical care to HIV
      patient in Spain. Origen study].
AB  - OBJECTIVES: To describe the structure, process and outcomes with which hospital
      pharmacist performs health care activity, teaching and research about
      Pharmaceutical Care (PC) in HIV patients in Spain. METHODS: Observational, cross
      sectional and multicenter study carried out between November 2011-February 2012
      in spanish hospitals. The inclusion criteria were: hospitals pharmacy services
      that dispensed antiretroviral medication to HIV patients. The questionnaire had
      41 questions structured in 9 groups: hospital type and person conducting the
      survey, structure and resources, health care activities, interventions,
      communication with the rest of the multidisciplinary team, adherence, and quality
      records, management and pharmacoeconomy and teaching and research. Descriptive
      analysis was performed. To analyze the existence of statistically significant
      relationships, we applied fisher test, chi-square or logistic regression.
      RESULTS: 86 hospitals completed the survey. In 93%, PC consultation was not
      classified by pathologies. 27.9% provided continuing PC to all patients.
      Adherence was determined regularly or when pharmacist suspected poor adherence
      (57.5 %). 20% of hospital s teaching had a program that allowed a high level of
      training in PC to HIV patient. 52,3% of participating centers had published
      scientific articles related to HIV. CONCLUSIONS: Pharmaceutical care to HIV
      patients in Spain need to adapt to a new situation. For this, hospital
      pharmacists have to consider several issues such as chronicity, comorbidity,
      incorporation of new technologies and the stratification of patients in order to
      make it more efficient.

PMID- 24669893
TI  - Use of Web 2.0 tools by hospital pharmacists.
AB  - OBJECTIVE: Web 2.0 tools are transforming the pathways health professionals use
      to communicate among themselves and with their patients so this situation forces
      a change of mind to implement them. The aim of our study is to assess the state
      of knowledge of the main Web 2.0 applications and how are used in a sample of
      hospital pharmacists. METHOD: The study was carried out through an anonymous
      survey to all members of the Spanish Society of Hospital Pharmacy (SEFH) by means
      of a questionnaire sent by the Google Drive(r) application. After the 3-month
      study period was completed, collected data were compiled and then analyzed using
      SPPS v15.0. RESULTS: The response rate was 7.3%, being 70.5% female and 76.3%
      specialists. The majority of respondents (54.2%) were aged 20 to 35. Pubmed was
      the main way of accessing published articles. 65.2% of pharmacists knew the term
      "Web 2.0". 45.3% pharmacists were Twitter users and over 58.9% mainly for
      professional purposes. Most pharmacists believed that Twitter was a good tool to
      interact with professionals and patients. 78.7% do not use an agregator, but when
      used, Google Reader was the most common. CONCLUSION: Although Web 2.0
      applications are gaining mainstream popularity some health professionals may
      resist using them. In fact, more than a half of surveyed pharmacists referred a
      lack of knowledge about Web 2.0 tools. It would be positive for pharmacists to
      use them properly during their professional practice to get the best out of them.

PMID- 24669894
TI  - [Use of the Six Sigma methodology for the preparation of parenteral nutrition
      mixtures].
AB  - OBJECTIVE: To use the tools of the Six Sigma methodology for the statistical
      control in the elaboration of parenteral nutrition mixtures at the critical
      checkpoint of specific density. METHODS: Between August of 2010 and September of
      2013, specific density analysis was performed to 100% of the samples, and the
      data were divided in two groups, adults and neonates. The percentage of
      acceptance, the trend graphs, and the sigma level were determined. A normality
      analysis was carried out by using the Shapiro Wilk test and the total percentage
      of mixtures within the specification limits was calculated. RESULTS: The specific
      density data between August of 2010 and September of 2013 comply with the
      normality test (W = 0.94) and show improvement in sigma level through time,
      reaching 6/6 in adults and 3.8/6 in neonates. 100% of the mixtures comply with
      the specification limits for adults and neonates, always within the control
      limits during the process. CONCLUSION: The improvement plans together with the
      Six Sigma methodology allow controlling the process, and warrant the agreement
      between the medical prescription and the content of the mixture.

PMID- 24669895
TI  - A better regulation is required in viral hepatitis smartphone applications.
AB  - AIM: To describe the characteristics and content of the available viral hepatitis
      mobile applications, as well as assess the level of participation of medical
      professionals in their development. METHODS: A descriptive observational study
      was carried out in September 2013. We searched smartphone apps specifically
      relating to the viral hepatitis for using a keyword search with the following
      terms; "hepatitis", "hepatology", "hbv" and "hcv" in the Google Play Store
      (Android) and the Apple App Store (iOS). Data recorded included: name, platform,
      category, cost, user star rating, number of downloads, date the app was updated
      by the developer and target audience. We analysed the content of the
      applications, and these were then categorised based on the viral hepatitis type
      into three groups. We conducted an analysis in which we specifically examined the
      authorship in order to assess the prevalence of health professional participation
      in their development. RESULTS: A total of 33 apps were included (from 232 that
      were identified), among which there were 10 duplicates. Most of these apps were
      uploaded under the medical category. Three had ratings less than 3.9 stars (out
      of 5). Only 6 apps had exceeded 1000 downloads. A total of 12 apps were aimed at
      health professionals, while 4 focused on patients (7 for both of them). The
      participation of health professionals in the development of apps was 56.6%.
      CONCLUSIONS: Viral hepatitis apps are available for both professionals and
      patients; however, much of the information contained within them is often not
      validated. They should be certificated.

PMID- 24669896
TI  - [Usage, effectiveness and safety of abiraterone in prostate cancer].
AB  - BACKGROUND AND OBJECTIVE: After the marketing of Abiraterone, an androgen
      synthesis inhibitor, the aim of the study was to analyze its use, response, and
      safety in the population of a tertiary care level hospital. MATERIALS AND
      METHODS: A retrospective observational study was carried out including all
      patients that were started on Abiraterone within a 21-month period.
      Demographical, diagnostic, therapeutic, and clinical variables were gathered. The
      response was assessed through the decreased of PSA as compared to baseline
      values. To assess the safety, all treatment-related adverse events were recorded.
      RESULTS: A total of 45 patients were included of which 88.89% could be assessed
      for the drug effectiveness. The median baseline PSA value was 457.31 (range 9032
      2.81). PSA decrease was >= 50%, >= 90% and < 30% in 16 (40%), 3 (7.5%) y 20
      (50%), respectively. The most common grade 1-2 adverse events were fatigue
      (35.6%), increased liver enzymes (28.9%), hipokalemia (13.3%) and fluid retention
      (11.1%). CONCLUSIONS: Abiraterone was a well tolerated drug that has shown to be
      active in prostate cancer patients previously treated with taxans, so it has been
      postulated as an alternative in this pathology.

PMID- 24669897
TI  - [Evaluation of the quality of scientific evidence of pharmaceutical interventions
      in an emergency department].
AB  - OBJECTIVES: To assess the quality of Pharmaceutical Interventions of starting a
      drug treatment based on the available scientific evidence, in an Emergency
      Department with a Clinical Pharmacist working full-time. To analyze the rate of
      Pharmaceutical Interventions over chronic or acute treatments and the ATC group
      of drugs involved. METHOD: The pharmacotherapy recommendations on Clinical
      Practice Guidelines (CPG) were classified and for every Pharmaceutical
      Intervention was assessed the quality of scientific evidence, strength of
      clinical recommendation, morbidity/mortality reduction, chronic or acute
      treatment and ATC group of drug involved. RESULTS: During the study period 2776
      Pharmaceutical Interventions were performed of which 47% were starting-drug
      interventions, being 73% justified with scientific evidence. The 84% of starting
      drug interventions were assessed with quality of evidence and strength of
      recommendation IA, 9% IC and 4% IB and 67% have been shown to reduce the
      morbidity/mortality according the CPG. 73% of interventions were related with
      patients' chronic treatment and ATC groups most frequently involved were N group
      (nervous system) and C group (cardiovascular system). In acute treatment the most
      frequent were B group and A group (Alimentary tract and metabolism). CONCLUSIONS:
      The starting-drug Pharmaceutical Interventions performed by an emergency
      department clinical pharmacist show a high adherence to CPG for most frequent
      pathologies, with good quality of evidence and good strength of recommendation as
      well as an associated morbidity/mortality reduction. Most starting-drug
      interventions were related to chronic treatment reconciliation, being drugs of N
      and C ATC group the most frequent involved.

PMID- 24669898
TI  - [Lapatinib plus transtuzumab for HER-2 positiva metastatic breast cancer:
      experience of use].
AB  - OBJECTIVE: To describe the outcomes produced by concomitant use of HER2-receptor
      inhibitors Lapatinib and Trastuzumab for the treatment of HER 2-positive
      metastatic breast cancer. METHOD: Retrospective observational study. Patients
      treated with Trastuzumab and Lapatinib between January of 2010 and May of 2012
      were selected. Demographical and clinical data were gathered. RESULTS: 23
      patients with metastatic breast cancer (mean age 59.3 +/- 13.3 years) were
      included. All of them had received an average of 5 treatment lines with at least
      one of them including Trastuzumab. The median progression-free survival rate with
      combined Lapatinib + Trastuzumab, with or without associated chemotherapy was 7
      months (95% CI: 2.78-11.21) and 3 months for the patients only receiving
      Lapatinib and Trastuzumab. Seven patients experienced adverse events and in four
      patients the treatment was stopped due to toxicity. CONCLUSIONS: The treatment
      with HER2-receptor inhibitors in our patients resulted in progression-free
      survival rates similar to those published in clinical trials with patients
      receiving Lapatinib + Trastuzumab not combined with any other anti-cancer
      therapy, with good treatment tolerability.

PMID- 24669899
TI  - [Set up of a protocol for heparin use in special patients].
AB  - Low-molecular weight (LMW) heparins bring a series of advantages as compared to
      non-fractionated heparin (NFH), such as safety, efficacy, bioavailability, fewer
      monitoring, and persistent anti-coagulant response. There exist, however, a
      concern about their use in particular patients that may require a special
      control, such as those with renal failure, age over 75 years, obesity, and
      pregnancy. The aim of this study was the set up between the department of
      Pharmacy, Hematology, and Internal Medicine of a consensus protocol for the
      follow-up ad monitoring of LMWH in patients requiring a special control. For this
      purpose, we carried out a bibliographical review of the different heparins used
      under de above mentioned conditions. Based on the evidence available and the
      consensus among the members of the working group, we established a protocol that
      contained recommendations on prophylaxis, management and monitoring by means of
      the determination of anti-Xa factor. Besides, we included some clues on the
      therapeutic figures of anti-Xa and administration schedules for obtaining anti-Xa
      values within the range. Enoxaparin was the selected heparin given the evidence
      and its availability at our center. 

PMID- 24669900
TI  - [Role of aprepitant in the management of pruritus in a patient with cutaneous T
      cell lymphoma].
AB  - - 

PMID- 24669901
TI  - [Clinical significance of the sodium content of intravenous antibiotic therapy].

PMID- 24669902
TI  - [Excipients of mandatory declaration (EMD): a non-resolved obligation].

PMID- 24669904
TI  - Low-solubility particles and a Trojan-horse type mechanism of toxicity: the case
      of cobalt oxide on human lung cells.
AB  - BACKGROUND: The mechanisms of toxicity of metal oxide particles towards lung
      cells are far from being understood. In particular, the relative contribution of
      intracellular particulate versus solubilized fractions is rarely considered as it
      is very challenging to assess, especially for low-solubility particles such as
      cobalt oxide (Co3O4). METHODS: This study was possible owing to two highly
      sensitive, independent, analytical techniques, based on single-cell analysis,
      using ion beam microanalysis, and on bulk analysis of cell lysates, using mass
      spectrometry. RESULTS: Our study shows that cobalt oxide particles, of very low
      solubility in the culture medium, are readily incorporated by BEAS-2B human lung
      cells through endocytosis via the clathrin-dependent pathway. They are partially
      solubilized at low pH within lysosomes, leading to cobalt ions release.
      Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected
      from these low-solubility particles, the intracellular solubilized cobalt content
      is small compared with the intracellular particulate cobalt content, in the parts
      per-thousand range or below. However, we were able to demonstrate that this
      minute fraction of intracellular solubilized cobalt is responsible for the
      overall toxicity. CONCLUSIONS: Cobalt oxide particles are readily internalized by
      pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan
      horse mechanism, to intracellular release of toxic metal ions over long periods
      of time, involving specific toxicity.

PMID- 24669905
TI  - Chromatin states reveal functional associations for globally defined
      transcription start sites in four human cell lines.
AB  - BACKGROUND: Deciphering the most common modes by which chromatin regulates
      transcription, and how this is related to cellular status and processes is an
      important task for improving our understanding of human cellular biology. The
      FANTOM5 and ENCODE projects represent two independent large scale efforts to map
      regulatory and transcriptional features to the human genome. Here we investigate
      chromatin features around a comprehensive set of transcription start sites in
      four cell lines by integrating data from these two projects. RESULTS:
      Transcription start sites can be distinguished by chromatin states defined by
      specific combinations of both chromatin mark enrichment and the profile shapes of
      these chromatin marks. The observed patterns can be associated with cellular
      functions and processes, and they also show association with expression level,
      location relative to nearby genes, and CpG content. In particular we find a
      substantial number of repressed inter- and intra-genic transcription start sites
      enriched for active chromatin marks and Pol II, and these sites are strongly
      associated with immediate-early response processes and cell signaling.
      Associations between start sites with similar chromatin patterns are validated by
      significant correlations in their global expression profiles. CONCLUSIONS: The
      results confirm the link between chromatin state and cellular function for
      expressed transcripts, and also indicate that active chromatin states at
      repressed transcripts may poise transcripts for rapid activation during immune
      response.

PMID- 24669906
TI  - Understanding safety in prehospital emergency medical services for children.
AB  - OBJECTIVE: For over a decade, the field of medicine has recognized the importance
      of studying and designing strategies to prevent safety issues in hospitals and
      clinics. However, there has been less focus on understanding safety in
      prehospital emergency medical services (EMS), particularly in regard to children.
      Roughly 27.7 million (or 27%) of the annual emergency department visits are by
      children under the age of 19, and about 2 million of these children reach the
      hospital via EMS. This paper adds to our qualitative understanding of the nature
      and contributors to safety events in the prehospital emergency care of children.
      METHODS: We conducted four 8- to 12-person focus groups among paid and volunteer
      EMS providers to understand 1) patient safety issues that occur in the
      prehospital care of children, and 2) factors that contribute to these safety
      issues (e.g., patient, family, systems, environmental, or individual provider
      factors). Focus groups were conducted in rural and urban settings. Interview
      transcripts were coded for overarching themes. RESULTS: Key factors and themes
      identified in the analysis were grouped into categories using an ecological
      approach that distinguishes between systems, team, child and family, and
      individual provider level contributors. At the systems level, focus group
      participants cited challenges such as lack of appropriately sized equipment or
      standardized pediatric medication dosages, insufficient human resources, limited
      pediatric training and experience, and aspects of emergency medical services
      culture. EMS team level factors centered on communication with other EMS
      providers (both prehospital and hospital). Family and child factors included
      communication barriers and challenging clinical situations or scene
      characteristics. Finally, focus group participants highlighted a range of
      provider level factors, including heightened levels of anxiety, insufficient
      experience and training with children, and errors in assessment and decision
      making. CONCLUSIONS: The findings of our study suggest that, just as in hospital
      medicine, factors at the systems, team, child/family, and individual provider
      level system contribute to errors in prehospital emergency care. These factors
      may be modifiable through interventions and systems improvements. Future studies
      are needed to ascertain the generalizability of these findings and further refine
      the underlying mechanisms.

PMID- 24669908
TI  - Oncoplastic breast surgery with latissimus dorsi myocutaneous flap for large
      defect in patients with ptotic breasts: is it feasible when combined with local
      flaps?
AB  - BACKGROUND: The latissimus dorsi myocutaneous flap (LDMCF) is frequently applied
      to breast cancer patients for breast reconstruction. However, the LDMCF is
      considered inappropriate for patients with ptotic breast. The authors
      investigated combining LDMCF and two local flaps for large defects of the breast
      after partial mastectomy in patients with ptosis. METHODS: Nineteen patients with
      breast cancer underwent a partial mastectomy with immediate reconstruction.
      Reconstruction methods consisted of LDMCF, thoraco-epigastric flap, and inferior
      pedicled rotational local flap, referred to as a combined pedicle flap. The
      cosmetic results were self-assessed after chemotherapy and radiotherapy by a four
      point scoring system. RESULTS: Ptosis was graded as follows: two patients with
      grade 1, 10 patients with grade 2, and seven patients with grade 3. The mean
      tumor size was 2.7 cm and multifocality was identified in 11 patients (57.9%).
      The mean excised volume was 468.5 cm3 and the percentage of excised volume was
      46.2%. The cosmetic results were excellent in five patients, good in seven
      patients, fair in six patients, and poor in one patient. CONCLUSION: The combined
      pedicle flap, consisting of LDMCF, thoraco-epigastric flap, and inferior pedicled
      rotational local flap, allows good cosmesis in breast cancer patients with large
      breasts or ptosis despite a wide excision.

PMID- 24669907
TI  - Ground reaction forces and osteogenic index of the sport of cyclocross.
AB  - Weight-bearing activity has been shown to increase bone mineral density. Our
      purpose was to measure vertical ground reaction forces (GRFs) during cyclocross
      specific activities and compute their osteogenic index (OI). Twenty-five healthy
      cyclocross athletes participated. GRF was measured using pressure-sensitive
      insoles during seated and standing cycling and four cyclocross-specific
      activities: barrier flat, barrier uphill, uphill run-up, downhill run-up. Peak
      and mean GRF values, according to bodyweight, were determined for each activity.
      OI was computed using peak GRF and number of loading cycles. GRF and OI were
      compared across activities using repeated-measures ANOVA. Number of loading
      cycles per activity was 6(1) for barrier flat, 8(1) barrier uphill, 7(1) uphill
      run-up, 12(3) downhill run-up. All activities had significantly (P < 0.01) higher
      peak GRF, mean GRF values and OI when compared to both seated and standing
      cycling. The barrier flat condition (P < 0.01) had highest peak (2.9 times
      bodyweight) and mean GRF values (2.3 times bodyweight). Downhill run-up (P <
      0.01) had the highest OI (6.5). GRF generated during the barrier flat activity is
      similar in magnitude to reported GRFs during running and hopping. Because
      cyclocross involves weight bearing components, it may be more beneficial to bone
      health than seated road cycling.

PMID- 24669909
TI  - Interleukin-8 and interleukin-17 for cancer.
AB  - Pro-inflammatory cytokines have been associated with chronic inflammation and
      inflammatory diseases. Increased levels of interleukins (ILs) have been
      associated with inflammatory disease exacerbation. ILs levels have been observed
      to be associated with advance stage cancer for several types of cancer and a poor
      prognostic maker for malignant disease. Moreover; increased levels of cytokines
      induce tumorigenesis. There are several paradigms such as the hepatocellular
      carcinoma induced from chronic inflammation of an underlying hepatitis. In the
      current review, we will focus on IL-8 and -17. These two ILs as in the case of
      others, induce neo-angiogenesis through activation of the vascular endothelial
      growth (VEGF) factor pathway. Additionally, they enhance the activity of matrix
      metalloproteinase-2 and -9 (MMP-2,-9) which in turn increase the metastatic
      activity of the underlying malignancy. Inhibition of cytokine production could be
      a potential treatment both for chronic inflammatory diseases and tumor
      modulation. Local microenvironment modulation could be applied in surgery
      resected patients as in the case of lung cancer in order to enhance the local
      immune activity.

PMID- 24669910
TI  - The inhibitory effect of salvianolic acid B on TGF-beta1-induced proliferation
      and differentiation in lung fibroblasts.
AB  - Salvianolic acid B (Sal B), one of the major water-soluble compounds of Danshen
      (a popular Chinese herb), possesses many of the biological activities, such as
      antifibrogenic effect in liver and renal diseases. Transforming growth factor
      beta1 (TGF-beta1) plays a central role in the development of pulmonary fibrosis
      by stimulating extracellular matrix (ECM) accumulation and activating
      fibroblasts. Here, we investigated the effects of Sal B on cell proliferation,
      collagen synthesis, endogenous TGF-beta1 production, and alpha-smooth muscle
      actin (alpha-SMA, a marker of myofibroblasts) expression in human lung
      fibroblasts stimulated by TGF-beta1 in vitro. The cell proliferation rates were
      analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide)
      assay. The expression of TGF-beta1 and type I collagen at both the mRNA and
      protein levels was detected by reverse transcription polymerase chain reaction
      (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay,
      respectively. The alpha-SMA expression was detected by Western blot. TGF-beta1
      treatment of lung fibroblasts increased cell proliferation rates, and enhanced
      the expression level of type I collagen, endogenous TGF-beta1 production, and
      alpha-SMA expression (P < .05). The treatment with only Sal B did not affect the
      proliferation and differentiation of lung fibroblasts. Interestingly, Sal B was
      found to inhibit TGF-beta1-induced cell proliferation, expression of type I
      collagen, endogenous TGF-beta1 production, and alpha-SMA expression in lung
      fibroblasts. Moreover, the inhibitory effect of Sal B on TGF-beta1-induced
      proliferation and differentiation in lung fibroblasts was more significant when
      treated with high-dose Sal B (1 MUmol/L versus 10 MUmol/L, P < .05). These data
      demonstrate that Sal B inhibits TGF-beta1-induced cell proliferation and
      differentiation in vitro experiment.

PMID- 24669911
TI  - Hepatitis C virus infection among HIV-positive men who have sex with men:
      protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Outbreaks of hepatitis C virus (HCV) infection have been reported in
      HIV-positive men who have sex with men (MSM) in North America, Europe and Asia.
      Transmission is believed to be the result of exposure to blood during sexual
      contact. In those infected with HIV, acute HCV infection is more likely to become
      chronic, treatment for both HIV and HCV is more complicated and HCV disease
      progression may be accelerated. There is a need for systematic reviews and meta
      analyses to synthesize the epidemiology, prevention and methods to control HCV
      infection in this population. METHODS/DESIGN: Eligible studies will include
      quantitative empirical data related to sexual transmission of HCV in HIV-positive
      MSM, including data describing incidence or prevalence, and associations between
      risk factors or interventions and the occurrence or progression of HCV disease.
      Care will be taken to ensure that HCV transmission related to injection drug use
      is excluded from the incidence estimates. Scientific databases will be searched
      using a comprehensive search strategy. Proceedings of scientific conferences,
      reference lists and personal files will also be searched. Quality ratings will be
      assigned to each eligible report using the Newcastle-Ottawa scale. Pooled
      estimates of incidence rates and measures of association will be calculated using
      random effects models. Heterogeneity will be assessed at each stage of data
      synthesis. DISCUSSION: HIV-positive MSM are a key HCV-affected population in the
      US and other high-income countries. This review seeks to identify modifiable risk
      factors and settings that will be the target of interventions, and will consider
      how to constitute a portfolio of interventions to deliver the greatest health
      benefit. This question must be considered in relation to the magnitude of HCV
      infection and its consequences in other key affected populations, namely, young
      prescription opioid users who have transitioned to illicit opiate injection, and
      older injection drug users among whom HCV prevalence and incidence are extremely
      high. This review is part of a series of systematic reviews and meta-analyses
      that will synthesize the evidence across all these population groups and develop
      recommendations and decision tools to guide public health resource allocation.
      TRIAL REGISTRATION: PROSPERO registration number: CRD42013006462.

PMID- 24669912
TI  - Pharmacokinetic-pharmacodynamic values for amoxicillin in pigs.

PMID- 24669915
TI  - Chondroprotective effects of zoledronic acid on articular cartilage in dogs with
      experimentally induced osteoarthritis.
AB  - OBJECTIVE: To assess effects of zoledronic acid on biomarkers, radiographic
      scores, and gross articular cartilage changes in dogs with induced
      osteoarthritis. ANIMALS: 21 purpose-bred hound-type dogs. PROCEDURES: The left
      stifle joint of each dog was examined arthroscopically to determine initial
      articular cartilage status, which was followed by cranial cruciate ligament
      (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups
      (control group, low dose [10 MUg of zoledronic acid/kg], or high dose [25 MUg of
      zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year
      beginning the day after CrCL transection. Serum and synovial fluid samples and
      radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12
      months, each joint was scored for cartilage defects. Serum and synovial fluid
      biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase,
      type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin
      sulfate 846) were analyzed with ELISAs. RESULTS: The high-dose group had fewer
      total articular defects and lower severity scores in CrCL-transected stifle
      joints than did the control group. In addition, the high-dose group had
      significantly less change in collagenase cleavage of type I or II collagen in the
      synovial fluid at 1 and 3 months after CrCL transection than did the control
      group and also had greater changes in bone-specific alkaline phosphatase in
      synovial fluid at 3 months after CrCL transection than did the control group.
      CONCLUSIONS AND CLINICAL RELEVANCE: Zoledronic acid had a chondroprotective
      effect in dogs with a transected CrCL.

PMID- 24669916
TI  - The effects of protamine sulfate on clot formation time and clot strength
      thromboelastography variables for canine blood samples.
AB  - OBJECTIVE: To determine the effects of protamine sulfate on clot formation time
      and clot strength thromboelastography variables for canine whole blood samples.
      ANIMALS: Blood samples obtained from 11 healthy dogs. PROCEDURES: Blood samples
      were collected from jugular veins of dogs into syringes with 3.2% sodium citrate
      (blood to citrate ratio, 9:1). Blood samples were divided into aliquots, and
      protamine sulfate was added to various concentrations (0 [control], 22, 44, and
      66 MUg/mL). Prepared samples were activated with kaolin (n = 8) or not activated
      (8), CaCl2 was added, and thromboelastography was performed. Reaction time (R),
      clot formation time (K), rate of clot formation (alpha angle), and maximum
      amplitude (MA) were measured. RESULTS: For kaolin-activated and nonactivated
      blood samples, protamine (66 MUg/mL) significantly increased R and K and
      decreased alpha angle and MA, compared with values for control samples. Also,
      protamine (44 MUg/mL) decreased MA in nonactivated blood samples and increased K
      and decreased alpha angle in kaolin-activated samples, compared with values for
      control samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated protamine
      prolonged clot formation time and decreased overall clot strength in a dose
      dependent manner; such effects may contribute to a hypocoagulable state in dogs.
      Kaolin-activated and nonactivated blood samples were appropriate for measurement
      of the effects of protamine on coagulation. Administration of protamine to
      reverse the effects of heparin should be performed with caution.

PMID- 24669917
TI  - Doppler ultrasonographic evaluation of renal arterial resistive and pulsatility
      indices in overhydrated Beagles.
AB  - OBJECTIVE: To determine renal arterial resistive index (RI) and pulsatility index
      (PI) and clinical signs of overhydration induced by IV administration of saline
      (0.9% NaCl) solution and to assess RI and PI as variables for monitoring of dogs
      to detect overhydration. ANIMALS: 10 clinically normal Beagles. PROCEDURES: Each
      dog received saline solution at a maintenance rate (2.5 mL/kg/h) and a rate 3
      times that of the maintenance rate (overhydration rate; 7. 5 mL/kg/h). Values of
      RI and PI were determined with pulsed-wave Doppler ultrasonographic examination
      of renal interlobar or arcuate arteries before saline solution administration,
      every hour during 5 hours of administration, and 1 hour after administration was
      stopped. RESULTS: No significant changes in RI or PI were detected during
      administration of saline solution at the maintenance rate. However, RI (starting
      1 hour after the beginning of fluid administration [mean +/- SD value, 0.589 +/-
      0.012]) and PI (starting 2 hours after the beginning of fluid administration
      [value, 0.867 +/- 0.052]) were significantly lower during administration at the
      overhydration rate than they were during administration at the maintenance rate.
      Clinical signs of overhydration were observed in all dogs starting 4 hours after
      the beginning of fluid administration at the overhydration rate. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicated overhydration of dogs caused significant
      decreases in RI and PI prior to detection of clinical signs of overhydration.
      Ultrasonographic determination of renal arterial RI and PI seemed to be a
      noninvasive and sensitive method for evaluation of overhydration in dogs.

PMID- 24669918
TI  - Ultrasonographic evaluation of the thickness of the wall layers in the intestinal
      tract of dogs.
AB  - OBJECTIVE: To ultrasonographically measure the thickness of the individual wall
      layers of the duodenum, jejunum, and colon of dogs. ANIMALS: 85 dogs with no
      clinical signs or ultrasonographic evidence of gastrointestinal tract disease.
      PROCEDURES: Total wall thickness and thickness of the mucosa, submucosa,
      muscularis, and serosa were measured ultrasonographically in the duodenum,
      jejunum, and colon of each dog. RESULTS: The mucosal layer was the thickest layer
      of the duodenum and jejunum. There was a significant difference in thickness of
      the mucosal layer between small and large dogs. Mean +/- SD thickness of the
      mucosal layer of the duodenum for small, medium, and large dogs was 2.4 +/- 0.5
      mm, 2.6 +/- 0.6 mm, and 2.8 +/- 0.5 mm, respectively. Mean +/- SD thickness of
      the mucosal layer of the jejunum for small, medium, and large dogs was 1.8 +/-
      0.4 mm, 2.0 +/- 0.4 mm, and 2.2 +/- 0.5 mm, respectively. The remaining wall
      layers of the duodenum and jejunum were similar in thickness, and there were no
      significant differences among small, medium, and large dogs. All layers
      contributed equally to the total colonic wall thickness. Mean +/- SD thickness of
      the colonic wall for small, medium, and large dogs was 1.5 +/- 0.3 mm, 1.4 +/-
      0.5 mm, and 1.6 +/- 0.4 mm, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      Values for thickness of the wall layers of the duodenum, jejunum, and colon of
      dogs reported here may be useful for assessing gastrointestinal tract diseases
      primarily targeting a specific wall layer.

PMID- 24669920
TI  - Evaluation of a technique for percutaneous endoscopic gastrostomy tube placement
      in horses.
AB  - OBJECTIVE: To develop and assess the short-term feasibility, maintenance, and
      complications associated with percutaneous endoscopic gastrostomy (PEG) tube
      placement in standing horses. ANIMALS: 6 adult horses. PROCEDURES: Feasibility of
      the technique was evaluated in 2 horses. In each of 4 other horses, a PEG tube
      was maintained for 14 days and used to provide fluid requirements during the
      latter 7 days, before removal. Following air inflation of the stomach, each PEG
      tube was placed via a left intercostal approach; proper tube location was
      ascertained by percutaneous ultrasonography and gastroscopy. The horses underwent
      physical examinations, CBCs, and peritoneal fluid analyses before and at
      intervals after tube placement. Seven days after tube removal, horses were
      euthanized and necropsied. RESULTS: Placement of a PEG tube was feasible in all 6
      horses. The 4 horses assessed long term tolerated water administration through
      the PEG tube and remained clinically stable throughout the 21-day experiment.
      However, during the period PEG tubes were in place, significant increases in some
      peritoneal and hematologic variables were detected. Postmortem evaluation
      revealed localized peritonitis in 1 horse and body wall inflammation along the
      PEG tube tracks in 3 additional horses. CONCLUSIONS AND CLINICAL RELEVANCE:
      Placement and maintenance of a PEG tube were tolerated well by the study horses,
      although peritoneal and systemic inflammation were detectable. Fluid requirements
      were adequately met with this technique, which could provide an alternative
      method for managing chronically dysphagic horses. Nevertheless, further research
      is warranted to evaluate the feasibility of enteral feeding by use of this
      approach in horses.

PMID- 24669921
TI  - High-resolution manometric evaluation of the effects of cisapride and
      metoclopramide hydrochloride administered orally on lower esophageal sphincter
      pressure in awake dogs.
AB  - OBJECTIVE: To evaluate the effects of cisapride and metoclopramide hydrochloride
      administered orally on the lower esophageal sphincter (LES) resting pressure in
      awake healthy dogs. ANIMALS: 6 adult Beagles. PROCEDURES: Each dog was evaluated
      after administration of a single dose of cisapride (0.5 mg/kg), metoclopramide
      (0.5 mg/kg), or placebo (empty gelatin-free capsule) in 3 experiments performed
      at 3-week intervals. To measure LES pressure, a high-resolution manometry
      catheter equipped with 40 pressure sensors spaced 10 mm apart was used. For each
      experiment, LES pressure was recorded during a 20-minute period with a virtual
      electronic sleeve emulation before treatment (baseline) and at 1, 4, and 7 hours
      after drug or placebo administration. A linear mixed-effects model was used to
      test whether the 3 treatments affected LES pressure differently. RESULTS: In the
      cisapride, metoclopramide, and placebo experiments, median baseline LES pressures
      were 29.1, 30.5, and 29.0 mm Hg, respectively. For the cisapride, metoclopramide,
      and placebo treatments, median LES pressures at 1 hour after administration were
      44.4, 37.8, and 36.6 mm Hg, respectively; median LES pressures at 4 hours after
      administration were 50.7, 30.6, and 31.1 mm Hg, respectively; and median LES
      pressures at 7 hours after administration were 44.3, 28.5, and 33.3 mm Hg,
      respectively. The LES pressures differed significantly only between the placebo
      and cisapride treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that orally administered cisapride may be of benefit in canine patients for which
      an increase in LES pressure is desirable, whereas orally administered
      metoclopramide did not affect LES resting pressures in dogs.

PMID- 24669923
TI  - Effect of a bandage or tendon boot on skin temperature of the metacarpus at rest
      and after exercise in horses.
AB  - OBJECTIVE: To determine the skin temperature of the metacarpus in horses
      associated with the use of bandages and tendon boots, compared with the bare
      limb, at rest and after 20 minutes of lunging. ANIMALS: 10 adult horses.
      PROCEDURES: Skin temperature on the bare metacarpus of both forelimbs was
      measured at rest and after lunging. Subsequently, a bandage was applied to the
      left metacarpus and a tendon boot to the right metacarpus and skin temperature
      was measured at rest and after lunging. Skin temperature was measured with fixed
      sensors and thermographically. RESULTS: Mean +/- SD skin temperatures of the bare
      metacarpi were 14.1 +/- 2.4 degrees C (left) and 14.1 +/- 3.4 degrees C (right)
      at rest, and 14.4 +/- 1.8 degrees C (left) and 13.6 +/- 2.6 degrees C (right)
      after exercise. Skin temperatures under the bandage were 15.3 +/- 1.6 degrees C
      at rest and 24.8 +/- 3.6 degrees C after exercise. Skin temperatures under the
      tendon boot were 15.3 +/- 2.6 degrees C at rest and 20.6 +/- 2.9 degrees C after
      exercise. Skin temperatures under the bandage and tendon boot were significantly
      higher after exercise than at rest. Skin temperatures at rest were not
      significantly different with a bare limb, bandage, or tendon boot. CONCLUSIONS
      AND CLINICAL RELEVANCE: Skin temperature of the metacarpus in horses increased
      significantly during exercise but not at rest when a bandage or tendon boot was
      used. The authors speculate that both a bandage and a tendon boot accelerate the
      warm up phase of exercise. Further research should focus on the effects of warm
      up and maximum exercise on the temperature of other anatomic structures such as
      tendons.

PMID- 24669922
TI  - Effect of short-term hyperinsulinemia on the localization and expression of
      endothelin receptors A and B in lamellar tissue of the forelimbs of horses.
AB  - OBJECTIVE: To determine the effect of short-term hyperinsulinemia on the
      localization and expression of endothelin receptor (ETR)-A and ETR-B in lamellar
      tissue of the forelimbs of horses. SAMPLES: Distal portion of 15 cadaveric
      forelimbs from healthy adult horses (1 limb/horse) obtained immediately after
      slaughter at an abattoir. PROCEDURES: Each forelimb was assigned to 1 of 3
      treatment groups (perfused with autologous blood for 10 hours [control perfusion;
      n = 5], perfused with an insulin [142 +/- 81 MUU/mL] perfusate for 10 hours
      [insulinemic perfusion; 5], or not perfused [unperfused control; 5]).
      Immunohistochemical evaluation of lamellar tissue was performed to assess
      localization of ETR-A and ETR-B. Expression of ETR-A and ETR-B was measured
      semiquantitatively on a scale of 0 to 3 (0 = none, 1 = mild, 2 = moderate, and 3
      = high-intensity staining) and quantitatively by means of gray value analysis
      with imaging software. RESULTS: In all specimens, ETR-A and ETR-B were localized
      in endothelium, smooth muscle cells, axons, and keratinocytes. Quantitative
      expression of ETR-A in the midportion of the primary epidermal lamellae for the
      insulinemic perfusion group (149 +/- 16) was lower than that for the control
      perfusion group (158 +/- 15). Expression of ETR-B in the primary epidermal
      lamellae tips for the insulinemic perfusion group (140 +/- 29) was higher than
      that for the control perfusion group (114 +/- 8). CONCLUSIONS AND CLINICAL
      RELEVANCE: Hyperinsulinemia caused significant changes in endothelin receptor
      expression, which suggested that ETR antagonists might be beneficial for
      treatment of laminitis in horses.

PMID- 24669924
TI  - Effects of ultraviolet radiation produced from artificial lights on serum 25
      hydroxyvitamin D concentration in captive domestic rabbits (Oryctolagus
      cuniculi).
AB  - OBJECTIVE: To determine the effects of UVB radiation produced by artificial
      lights on serum 25-hydroxyvitamin D concentrations in domestic rabbits
      (Oryctolagus cuniculi). ANIMALS: 9 juvenile domestic rabbits. PROCEDURES: After
      an acclimation period, rabbits were anesthetized with isoflurane, and an initial
      blood sample was collected for determination of serum 25-hydroxyvitamin D
      concentration. Rabbits were randomly assigned to receive 12-hour exposure to UVB
      radiation produced by 2 compact fluorescent lights daily (n = 5) or no UVB
      supplementation (4) commencing on day 1. The UVB radiation emitted into the cage
      was measured at 9 points approximately 34 cm from the surface of the UVB light
      sources (representing the position of the rabbits in the cage) after 10 hours of
      exposure on days 1, 8, and 14. On day 14, another blood sample was collected from
      anesthetized rabbits for determination of serum 25-hydroxyvitamin D
      concentration. RESULTS: The UVB radiation level was 8.3 to 58.1 MUW/cm2 for the
      exposed rabbits and consistently < 0.001 MUW/cm2 for the control rabbits. Mean +/
      SD serum 25-hydroxyvitamin D concentrations in the rabbits that were or were not
      provided supplemental UVB radiation for 14 days differed significantly (66.4 +/-
      14.3 nmol/L and 31.7 +/- 9.9 nmol/L, respectively). CONCLUSIONS AND CLINICAL
      RELEVANCE: Exposure to UVB radiation produced by artificial light significantly
      increased serum 25-hydroxyvitamin D concentration in juvenile rabbits. Because
      vitamin D is an essential hormone in vertebrates, these findings suggested that
      the provision of supplemental UVB radiation to captive rabbits may be important.

PMID- 24669925
TI  - Effects of experimental mechanical manipulations on local inflammation in the
      jejunum of horses.
AB  - OBJECTIVE: To determine characteristics of the inflammatory reaction in the
      jejunum of horses in response to various mechanical manipulations. ANIMALS: 12
      adult warm blood horses without gastrointestinal tract disorders. PROCEDURES: The
      proximal aspect of the jejunum in each horse was divided into 5 segments, and the
      following manipulations were performed: manual emptying, placement of Doyen
      forceps, enterotomy alone, enterotomy with mucosal abrasion, and serosal
      abrasion. Jejunum samples were collected before (control), immediately after, and
      30 minutes after the end of manipulations and histologically evaluated to
      determine distribution of neutrophils and eosinophils. RESULTS: Macroscopically,
      all manipulations resulted in jejunal hemorrhage and edema. Compared with control
      samples, neutrophil numbers were significantly higher after manipulations in the
      serosa (after all manipulation types), circular muscle layer (after manual
      emptying), submucosa (after placement of Doyen forceps), and mucosa (after all
      manipulations except enterotomy alone). Eosinophil numbers were significantly
      higher in the submucosa after mechanical abrasion of the serosa and manual
      emptying versus control samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated mechanical manipulation of the jejunum resulted in local inflammatory
      reactions characterized predominantly by infiltration of neutrophils. This could
      contribute to the development of postoperative ileus or adhesions in horses
      without macroscopically detectable injury of the jejunum during surgery.

PMID- 24669926
TI  - Ultrastructure and growth factor content of equine platelet-rich fibrin gels.
AB  - OBJECTIVE: To compare fiber diameter, pore area, compressive stiffness, gelation
      properties, and selected growth factor content of platelet-rich fibrin gels
      (PRFGs) and conventional fibrin gels (FGs). SAMPLE: PRFGs and conventional FGs
      prepared from the blood of 10 healthy horses. PROCEDURES: Autologous fibrinogen
      was used to form conventional FGs. The PRFGs were formed from autologous platelet
      rich plasma of various platelet concentrations (100 * 103 platelets/MUL, 250 *
      103 platelets/MUL, 500 * 103 platelets/MUL, and 1,000 * 103 platelets/MUL). All
      gels contained an identical fibrinogen concentration (20 mg/mL). Fiber diameter
      and pore area were evaluated with scanning electron microscopy. Maximum gelation
      rate was assessed with spectrophotometry, and gel stiffness was determined by
      measuring the compressive modulus. Gel weights were measured serially over 14
      days as an index of contraction (volume loss). Platelet-derived growth factor-BB
      and transforming growth factor-beta1 concentrations were quantified with ELISAs.
      RESULTS: Fiber diameters were significantly larger and mean pore areas were
      significantly smaller in PRFGs than in conventional FGs. Gel weight decreased
      significantly over time, differed significantly between PRFGs and conventional
      FGs, and was significantly correlated with platelet concentration. Platelet
      derived growth factor-BB and transforming growth factor-beta1 concentrations were
      highest in gels and releasates derived from 1,000 * 103 platelets/MUL.
      CONCLUSIONS AND CLINICAL RELEVANCE: The inclusion of platelets in FGs altered the
      architecture and increased the growth factor content of the resulting scaffold.
      Platelets may represent a useful means of modifying these gels for applications
      in veterinary and human regenerative medicine.

PMID- 24669927
TI  - Surgical insertion of transmitters and telemetry methods in fisheries research.

PMID- 24669928
TI  - Decadal trends reveal recent acceleration in the rate of recovery from
      acidification in the northeastern U.S.
AB  - Previous reports suggest variable trends in recovery from acidification in
      northeastern U.S. surface waters in response to the Clean Air Act Amendments.
      Here we analyze recent trends in emissions, wet deposition, and lake chemistry
      using long-term data from a variety of lakes in the Adirondack Mountains and New
      England. Sulfate concentration in wet deposition declined by more than 40% in the
      2000s and sulfate concentration in lakes declined at a greater rate from 2002 to
      2010 than during the 1980s or 1990s (-3.27 MUeq L(-1)year(-1) as compared to 
      1.26 MUeq L(-1)year(-1)). During the 2000s, nitrate concentration in wet
      deposition declined by more than 50% and nitrate concentration in lakes, which
      had no linear trend prior to 2000, declined at a rate of -0.05 MUeq L(-1)year(
      1). Base cation concentrations, which decreased during the 1990s (-1.5 MUeq L(-1)
      year(-1)), have stabilized in New England lakes. Although total aluminum
      concentrations increased since 1999 (2.57 MUg L(-1) year(-1)), there was a shift
      to nontoxic, organic aluminum. Despite this recent acceleration in recovery in
      multiple variables, both ANC and pH continue to have variable trends. This may be
      due in part to variable trajectories in the concentrations of base cations and
      dissolved organic carbon among our study lakes.

PMID- 24669929
TI  - Gastrointestinal stromal tumor with nephrotic syndrome as a paraneoplastic
      syndrome: a case report.
AB  - INTRODUCTION: Paraneoplastic syndromes are disorders associated with clinical
      signs and symptoms caused by substances produced by malignant disease and are not
      directly related to the physical effects of a primary or metastatic tumor. We
      describe a patient with gastrointestinal stromal tumor of the stomach accompanied
      by nephrotic syndrome as paraneoplastic syndrome in whom symptomatic treatment
      was ineffective. Nephrotic syndrome caused by gastrointestinal stromal tumors is
      quite rare, and to the best of our knowledge this is the first time that such a
      case has been documented. CASE PRESENTATION: We describe a 69-year-old Asian
      woman with a gastrointestinal stromal tumor of the stomach accompanied by
      paraneoplastic syndrome. The patient had severe hypoalbuminemia and proteinuria,
      which were apparently attributed to a gastrointestinal stromal tumor. After
      preoperative treatment for hypoalbuminemia, the tumor was resected and nephrotic
      syndrome improved. Two years after her operation, she is still alive with neither
      tumor recurrence nor nephrotic syndrome. CONCLUSION: Patients with refractory
      nephrotic syndrome caused by a malignant tumor should be treated aggressively,
      even if they are in poor general condition. Otherwise, the opportunity for
      potentially curative surgery may be missed.

PMID- 24669930
TI  - Nanoscale metal-organic frameworks for the co-delivery of cisplatin and pooled
      siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells.
AB  - Ovarian cancer is the leading cause of death among women with gynecological
      malignancies. Acquired resistance to chemotherapy is a major limitation for
      ovarian cancer treatment. We report here the first use of nanoscale metal-organic
      frameworks (NMOFs) for the co-delivery of cisplatin and pooled small interfering
      RNAs (siRNAs) to enhance therapeutic efficacy by silencing multiple drug
      resistance (MDR) genes and resensitizing resistant ovarian cancer cells to
      cisplatin treatment. UiO NMOFs with hexagonal-plate morphologies were loaded with
      a cisplatin prodrug and MDR gene-silencing siRNAs (Bcl-2, P-glycoprotein [P-gp],
      and survivin) via encapsulation and surface coordination, respectively. NMOFs
      protect siRNAs from nuclease degradation, enhance siRNA cellular uptake, and
      promote siRNA escape from endosomes to silence MDR genes in cisplatin-resistant
      ovarian cancer cells. Co-delivery of cisplatin and siRNAs with NMOFs led to an
      order of magnitude enhancement in chemotherapeutic efficacy in vitro, as
      indicated by cell viability assay, DNA laddering, and Annexin V staining. This
      work shows that NMOFs hold great promise in the co-delivery of multiple
      therapeutics for effective treatment of drug-resistant cancers. 

PMID- 24669932
TI  - Microwave Heating Inactivates Shiga Toxin (Stx2) in Reconstituted Fat-Free Milk
      and Adversely Affects the Nutritional Value of Cell Culture Medium.
AB  - Microwave exposure is a convenient and widely used method for defrosting,
      heating, and cooking numerous foods. Microwave cooking is also reported to kill
      pathogenic microorganisms that often contaminate food. In this study, we tested
      whether microwaves would inactivate the toxicity of Shiga toxin 2 (Stx2) added to
      5% reconstituted fat-free milk administered to monkey kidney Vero cells. Heating
      of milk spiked with Stx2 in a microwave oven using a 10% duty cycle (cycle period
      of 30 s) for a total of 165 kJ energy or thermal heating (pasteurization), widely
      used to kill pathogenic bacteria, did not destroy the biological effect of the
      toxin in the Vero cells. However, conventional heating of milk to 95  degrees C
      for 5 min or at an increased microwave energy of 198 kJ reduced the Stx2
      activity. Gel electrophoresis showed that exposure of the protein toxin to high
      energy microwaves resulted in the degradation of its original structure. In
      addition, two independent assays showed that exposure of the cell culture medium
      to microwave energy of 198 kJ completely destroyed the nutritional value of the
      culture medium used to grow the Vero cells, possibly by damaging susceptible
      essential nutrients present in the medium. These observations suggest that
      microwave heating has the potential to destroy the Shiga toxin in liquid food.

PMID- 24669931
TI  - Compound heterozygous mutations in glycyl-tRNA synthetase are a proposed cause of
      systemic mitochondrial disease.
AB  - BACKGROUND: Glycyl-tRNA synthetase (GARS) is an aminoacyl-tRNA synthetase (ARS)
      that links the amino acid glycine to its corresponding tRNA prior to protein
      translation and is one of three bifunctional ARS that are active within both the
      cytoplasm and mitochondria. Dominant mutations in GARS cause rare forms of
      Charcot-Marie-Tooth disease and distal spinal muscular atrophy. CASE
      PRESENTATION: We report a 12-year old girl who presented with clinical and
      biochemical features of a systemic mitochondrial disease including exercise
      induced myalgia, non-compaction cardiomyopathy, persistent elevation of blood
      lactate and alanine and MRI evidence of mild periventricular leukomalacia. Using
      exome sequencing she was found to harbor compound heterozygous mutations within
      the glycyl-tRNA synthetase (GARS) gene; c.1904C > T; p.Ser635Leu and c.1787G > A;
      p.Arg596Gln. Each mutation occurred at a highly conserved site within the
      anticodon binding domain. CONCLUSION: Our findings suggest that recessive
      mutations in GARS may cause systemic mitochondrial disease. This phenotype is
      distinct from patients with previously reported dominant mutations in this gene,
      thereby expanding the spectrum of disease associated with GARS dysregulation.

PMID- 24669933
TI  - Evaluation of the national prevention program in iran, 2007-2009: the
      accomplishments and challenges with reflections on the path ahead.
AB  - beta-Thalassemia major (beta-TM) is an inherited disease and efforts have been
      made in several countries to reduce the number of affected births. In the present
      study, we aimed to evaluate the Iranian thalassemia prevention program,
      considered to be an important program in the region. The time period of the
      present study ranges from 2007-2009, during which new thalassemic births and the
      relevant causes were evaluated throughout the country. A cross-sectional
      analytical study was conducted at the Iranian Blood Transfusion Organization
      (IBTO), Tehran, Iran. A questionnaire was forwarded to all blood centers of the
      IBTO so as to obtain information about the new cases of thalassemia and the
      causes of these thalassemic births. Provincial thalassemia societies also
      received the questionnaires so that screening and prenatal diagnosis (PND) errors
      would be recorded. The results showed that 755 new thalassemia cases were born
      during 2007-2009 with the average fall in affected thalassemia births of 80.82%.
      The main cause of the new births was attributed to unregistered "timeless
      religious marriages" based on the conventions of the Sunni community which
      accounted for 43.17% of all new cases mainly having occurred in Sistan &
      Baluchestan Province. Not using PND was evaluated to be another main cause.
      Although the prevention program has led to a great reduction in thalassemic
      births, new measures are required, including research on how to make the program
      compatible with social and economic conventions and norms of Sistan & Baluchestan
      Province. The province of Kohgiluyeh Boyer Ahmad also needs to be revisited in
      terms of the program efficacy.

PMID- 24669934
TI  - Extracellular vesicles released from mesenchymal stromal cells modulate miRNA in
      renal tubular cells and inhibit ATP depletion injury.
AB  - The mechanisms involved in renal repair by mesenchymal stromal cells (MSCs) are
      not entirely elucidated. The paracrine secretion of bioactive molecules has been
      implicated in the protective effects. Besides soluble mediators, MSCs have been
      shown to release extracellular vesicles (EVs), involved in renal repair process
      for different injury models. EVs have been shown to mediate communication between
      cells through the transference of several molecules, like protein, bioactive
      lipids, mRNA, and microRNAs (miRNAs). The miRNAs are noncoding RNAs that
      posttranscriptionally modulate gene expression and are involved in the regulation
      of several cellular processes, including those related to repair. The aim of the
      present study was to investigate the role of MSC-EVs in the modulation of miRNAs
      inside renal proximal tubular epithelial cells (PTECs) in an in vitro model of
      ischemia-reperfusion injury induced by ATP depletion. In this model we evaluated
      whether changes in miRNA expression were dependent on direct miRNA transfer or on
      transcription induction by MSC-EVs. The obtained results showed an enhanced
      incorporation of MSC-EVs in injured PTECs with protection from cell death. This
      biological effect was associated with EV-mediated miRNA transfer and with
      transcriptional modulation of miRNAs expressed by injured PTECs. Prediction of
      miRNA targets showed that miRNAs modulated in PTECs are involved in process of
      renal recovery with downregulation of coding-mRNAs associated with apoptosis,
      cytoskeleton reorganization, and hypoxia, such as CASP3 and 7, SHC1 and SMAD4. In
      conclusion, these results indicate that MSC-EVs may transfer and modulate the
      expression of several miRNAs involved in the repair and recovery process in
      PTECs. 

PMID- 24669935
TI  - Pepper spray injury severity: ten-year case experience of a poison control
      system.
AB  - BACKGROUND: Pepper spray is a common lacrimator used by law enforcement and the
      public to subdue individuals and for self-defense. The risk factors for severe
      injury due to pepper spray exposure are not well documented and there is a lack
      of guidelines to identify patients that require transport and medical evaluation
      in an emergency department. OBJECTIVE: The aim of this study was to determine the
      prevalence of and circumstances associated with symptoms suggestive of tissue
      injury beyond transient irritation in persons exposed to pepper spray. METHODS:
      We reviewed all human exposures to pepper spray reported to a poison control
      system between 2002 and 2011. Cases were differentiated into 2 outcome groups:
      minor or self-limiting symptoms versus those with more severe symptoms suggestive
      of tissue injury that warranted a medical evaluation. A comparison of the
      variables between the outcome groups was performed using odds ratios (ORs), 95%
      confidence intervals (CIs), and associated P values. RESULTS: A total of 4,544
      cases were identified and 3,671 met the inclusion criteria. Of these, 249 cases
      (6.8%) were found to have more severe symptoms that warranted a medical
      evaluation. There were no reported deaths. The cases with more severe symptoms
      most commonly involved the ocular (53.8%), respiratory (31.7%), and dermal
      (17.7%) organ systems. Factors with largest independent associations with more
      severe outcomes were use for law enforcement training (OR, 7.39; 95% CI, 2.98
      18.28), direct intentional exposure for purposeful use to incapacitate (OR, 3.02;
      95% CI, 1.80-5.06), and for law enforcement on individual target suspects or
      crowd control (OR, 2.45; 95% CI, 1.42-4.23). CONCLUSIONS: There was a low 1 in 15
      potential risk for more severe adverse health effects in persons exposed to
      pepper spray that warranted a medical evaluation. The risk was highest when used
      for training of law enforcement personnel and involved severe ocular symptoms.
      This suggests that routine use of pepper spray for training of law enforcement or
      military personnel be reconsidered. Protective goggles may be an option when
      direct spraying into the face of trainees. Transport for medical evaluation
      should be considered for exposed persons that manifest persistent ocular or
      respiratory symptoms.

PMID- 24669936
TI  - Emerging drugs for the treatment of gastroparesis.
AB  - INTRODUCTION: Gastroparesis presents with symptoms of gastric retention with
      findings of delayed gastric emptying on diagnostic testing. Manifestations of
      gastroparesis are disabling in severe cases and lead to significant health
      resource utilization. Current therapies often are ineffective, may exhibit
      tolerance on chronic administration or produce prominent side effects in large
      patient subsets. AREAS COVERED: This review assessed literature on drugs with
      theoretical efficacy in gastroparesis including medications that accelerate
      gastric emptying, reduce nausea and vomiting, or act as neuromodulators to reduce
      gastric sensitivity. Numerous agents exhibit diverse actions to modify gastric
      sensorimotor function in animal models; however, few medications are in
      controlled testing in gastroparesis. Prokinetic drugs with promise for this
      condition include investigational serotonin 5-HT4 agonists, motilin agonists,
      dopamine D2 antagonists, ghrelin agonists and an agent with combined muscarinic
      antagonist and acetylcholinesterase inhibitory effects. Other antiemetics and
      complementary and alternative formulations may be effective for some symptoms.
      EXPERT OPINION: Development of effective novel therapies of gastroparesis without
      the neurotoxicity and cardiac arrhythmogenic effects of current agents will
      mandate a better definition of the gastric and extragastric factors responsible
      for the pathogenesis of the varied clinical manifestations of this disorder.

PMID- 24669937
TI  - Protocol for a systematic review and economic evaluation of the clinical and cost
      effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients
      with stable end-stage COPD with hypercapnic respiratory failure.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a significant
      public health burden. Non-invasive ventilation (NIV) is a method of supported
      breathing used as standard care for acutely unwell patients in hospital with
      COPD, but there is uncertainty around the potential benefits of using NIV in the
      treatment of stable patients in a non-hospital setting. This is a protocol for
      systematic reviews of the clinical and cost-effectiveness of NIV in this context,
      being undertaken in support of a model based economic evaluation. METHODS/DESIGN:
      Standard systematic review methods aimed at minimising bias will be employed for
      study identification, selection and data extraction for both the clinical and
      economic systematic reviews. Bibliographic databases (for example MEDLINE,
      EMBASE) and ongoing trials registers will be searched from 1980 onwards. The
      search strategy will combine terms for the population with those for the
      intervention. Studies will be selected for review if the population includes
      adult patients with COPD and hypercapnic respiratory failure, however defined.
      Systematic reviews, randomised controlled trials and observational studies (with
      n >1) will be included, and quality assessment will be tailored to the different
      study designs. The primary outcome measures of interest are survival, quality of
      life, and healthcare utilisations (hospitalisation and Accident and Emergency
      attendances). Meta-analyses will be undertaken where clinical and methodological
      homogeneity exists, supported by predefined subgroup analyses where appropriate.
      A systematic review of the evidence on the cost-effectiveness of non-hospital NIV
      will be completed, and a model-based cost-utility analysis undertaken to
      determine the cost-effectiveness of non-hospital-based NIV compared with standard
      care. DISCUSSION: These reviews will attempt to clarify the clinical
      effectiveness of non-hospital NIV in COPD patients as well as the cost
      effectiveness. The findings may indicate whether NIV in a non-hospital setting
      should be considered more routinely in this patient group, and what the likely
      cost implications will be. PROSPERO REGISTRATION: 2012:CRD42012003286.

PMID- 24669938
TI  - Discovery of a highly tumor-selective organometallic ruthenium(II)-arene complex.
AB  - A ruthenium(II)-arene complex with a perfluoroalkyl-ligand was found to display
      remarkable selectivity toward cancer cells. IC50 values on several cancer cell
      lines are in the range of 25-45 MUM, and no cytotoxic effect was observed on
      nontumorigenic (HEK-293) cells at concentrations up to 500 MUM (the maximum
      concentration tested). Consequently, this complex was used as the basis for the
      development of a number of related derivatives, which were screened in cancerous
      and noncancerous cell lines. The lead compound was then evaluated in vivo for
      antiangiogenic activity in the CAM model and in a xenografted ovarian carcinoma
      tumor (A2780) grown on the CAM. A 90% reduction in the tumor growth was observed.

PMID- 24669939
TI  - Aggressive mature natural killer cell neoplasms: report on a series of 12
      European patients with emphasis on flow cytometry based immunophenotype and DNA
      content of neoplastic natural killer cells.
AB  - We report 12 cases of aggressive natural killer (NK) cell neoplasms diagnosed in
      Portugal, with emphasis on flow cytometry. Ten patients had extranodal NK/T cell
      lymphoma, nasal type and two had aggressive NK cell leukemia, and seven were men
      and five were women, with a median age of 50 years. NK cells brightly expressed
      the CD56 adhesion molecule and CD94 lectin type killer receptor and had an
      activation-related HLA-DR+ CD45RA+ CD45RO+ immunophenotype, in most cases. In
      contrast, dim CD16 expression was found in a minor proportion of cases, whereas
      CD57 and the CD158a and CD158e1 killer immunoglobulin-like receptors were
      negative. One-third of cases showed a hyperploid DNA content and nearly all had a
      very high S-phase proliferative rate. The phenotypic features of the neoplastic
      NK cells would suggest that they represent the transformed counterpart of the
      CD56 + bright NK cells that circulate in normal blood.

PMID- 24669940
TI  - Minimally invasive endoscopic treatment for lumbar infectious spondylitis: a
      retrospective study in a tertiary referral center.
AB  - BACKGROUND: Spinal infections remain a challenge for clinicians because of their
      variable presentation and complicated course. Common management approaches
      include conservative administration of antibiotics or aggressive surgical
      debridement. The purpose of this study was to evaluate the efficacy of
      percutaneous endoscopic debridement with dilute betadine solution irrigation
      (PEDI) for treating patients with lumbar infectious spondylitis. METHODS: From
      January 2005 to July 2010, a total of 32 patients undergoing PEDI were
      retrospectively enrolled in this study. The surgical indications of the enrolled
      patients included single-level infectious spondylodiscitis, postoperative
      infectious spondylodiscitis, advanced infection with epidural abscess, psoas
      muscle abscess, pre-vertebral or para-vertebral abscess, multilevel infectious
      spondylitis, and recurrent infection after anterior debridement and fusion.
      Clinical outcomes were assessed by careful physical examination, Macnab criteria,
      regular serologic testing, and imaging studies to determine whether continued
      antibiotics treatment or surgical intervention was required. RESULTS: Causative
      bacteria were identified in 28 (87.5%) of 32 biopsy specimens. Appropriate
      parenteral antibiotics for the predominant pathogen isolated from infected tissue
      biopsy cultures were prescribed to patients. Twenty-seven (84.4%) patients
      reported satisfactory relief of their back pain after PEDI. Twenty-six (81.3%)
      patients recovered uneventfully after PEDI and sequential antibiotic therapy. No
      surgery-related major complications were found, except 3 patients with transient
      paresthesia in the affected lumbar segment. CONCLUSIONS: PEDI was successful in
      obtaining a bacteriologic diagnosis, relieving the patient's symptoms, and
      assisting in the eradication of lumbar infectious spondylitis. This procedure
      could be an effective alternative for patients who have a poor response to
      conservative treatment before a major open surgery.

PMID- 24669941
TI  - Structural and kinetic characterization of guinea pig L-asparaginase type III.
AB  - We investigated whether an uncharacterized protein from guinea pig could be the
      enzyme behind Kidd's serendipitous discovery, made over 60 years ago, that guinea
      pig serum has cell killing ability. It has been long known that an enzyme with l
      asparaginase activity is responsible for cell killing, although astonishingly,
      its identity remains unclear. Bacterial asparaginases with similar cell killing
      properties have since become a mainstay therapy of certain cancers such as acute
      lymphoblastic leukemia. By hydrolyzing asparagine to aspartate and ammonia, these
      drugs deplete the asparagine present in the blood, killing cancer cells that rely
      on extracellular asparagine uptake for survival. However, bacterial asparaginases
      can elicit an adverse immune response. We propose that replacement of bacterial
      enzymes with the guinea pig asparaginase responsible for serum activity, by its
      virtue of being more closely related to human enzymes, will be less immunogenic.
      To this goal, we investigated whether an uncharacterized protein from guinea pig
      with putative asparaginase activity, which we call gpASNase3, could be that
      enzyme. We examined its self-activation process (gpASNase3 requires autocleavage
      to become active), kinetically characterized it for asparaginase and beta
      aspartyl dipeptidase activity, and elucidated its crystal structure in both the
      uncleaved and cleaved states. This work reveals that gpASNase3 is not the enzyme
      responsible for the antitumor effects of guinea pig serum. It exhibits a low
      affinity for asparagine as measured by a high Michaelis constant, KM, in the
      millimolar range, in contrast to the low KM (micromolar range) required for
      asparaginase to be effective as an anticancer agent. 

PMID- 24669943
TI  - AApoAIL75P amyloidosis causes cirrhosis-like appearance of the liver in the
      absence of laboratory or clinical signs of hepatic dysfunction.

PMID- 24669944
TI  - Textural and Rheological Properties of Oat Beta-Glucan Gels with Varying
      Molecular Weight Composition.
AB  - The impact of oat beta-glucan concentration and molecular weight (MW) on gel
      properties was investigated. Mixed MW gels/viscous solutions at 3, 4, and 5% beta
      glucan with high molecular weight (HMW):low molecular weight (LMW) ratios of
      0:100, 25:75, 50:50, 75:25, and 100:0 were evaluated. The 100:0 and 50:50 gels
      had the lowest tan delta values. The 50:50 gels had the highest storage moduli
      (G'), whereas 100:0 solutions did not gel. Peak melting temperature (TP) was
      highest for 0:100 gels and decreased with the addition of HMW beta-glucan.
      Hardness, at 40% compression, increased with concentration, and 25:75 and 50:50
      gels were hardest at each concentration. Ordered microstructure, apparent in
      0:100 gels, diminished with HMW beta-glucan addition. Glucose addition resulted
      in lower tan delta values and firmer, harder gels compared to gels without
      glucose. Thus, the textural properties and melting profiles of beta-glucan gels
      can be manipulated by adjusting the ratios of molecular weight fractions or
      addition of sugar for different applications.

PMID- 24669942
TI  - Alternative splicing of type II procollagen: IIB or not IIB?
AB  - Over two decades ago, two isoforms of the type II procollagen gene (COL2A1) were
      discovered. These isoforms, named IIA and IIB, are generated in a developmentally
      regulated manner by alternative splicing of exon 2. Chondroprogenitor cells
      synthesize predominantly IIA isoforms (containing exon 2) while differentiated
      chondrocytes produce mainly IIB transcripts (devoid of exon 2). Importantly, this
      IIA-to-IIB alternative splicing switch occurs only during chondrogenesis. More
      recently, two other isoforms have been reported (IIC and IID) that also involve
      splicing of exon 2; these findings highlight the complexities involving
      regulation of COL2A1 expression. The biological significance of why different
      isoforms of COL2A1 exist within the context of skeletal development and
      maintenance is still not completely understood. This review will provide current
      knowledge on COL2A1 isoform expression during chondrocyte differentiation and
      what is known about some of the mechanisms that control exon 2 alternative
      splicing. Utilization of mouse models to address the biological significance of
      Col2a1 alternative splicing in vivo will also be discussed. From the knowledge
      acquired to date, some new questions and concepts are now being proposed on the
      importance of Col2a1 alternative splicing in regulating extracellular matrix
      assembly and how this may subsequently affect cartilage and endochondral bone
      quality and function.

PMID- 24669945
TI  - The political economy of farmers' suicides in India: indebted cash-crop farmers
      with marginal landholdings explain state-level variation in suicide rates.
AB  - BACKGROUND: A recent Lancet article reported the first reliable estimates of
      suicide rates in India. National-level suicide rates are among the highest in the
      world, but suicide rates vary sharply between states and the causes of these
      differences are disputed. We test whether differences in the structure of
      agricultural production explain inter-state variation in suicides rates. This
      hypothesis is supported by a large number of qualitative studies, which argue
      that the liberalization of the agricultural sector in the early-1990s led to an
      agrarian crisis and that consequently farmers with certain socioeconomic
      characteristics-cash crops cultivators, with marginal landholdings, and debts-are
      at particular risk of committing suicide. The recent Lancet study, however,
      contends that there is no evidence to support this hypothesis. METHODS: We report
      scatter diagrams and linear regression models that combine the new state-level
      suicide rate estimates and the proportion of marginal farmers, cash crop
      cultivation, and indebted farmers. RESULTS: When we include all variables in the
      regression equation there is a significant positive relationship between the
      percentage of marginal farmers, cash crop production, and indebted farmers, and
      suicide rates. This model accounts for almost 75% of inter-state variation in
      suicide rates. If the proportion of marginal farmers, cash crops, or indebted
      farmers were reduced by 1%, the suicide rate--suicides per 100,000 per year-
      would fall by 0 . 437, 0 . 518 or 0 . 549 respectively, when all other variables
      are held constant. CONCLUSIONS: Even if the Indian state is unable to enact land
      reforms due to the power of local elites, interventions to stabilize the price of
      cash crops and relieve indebted farmers may be effective at reducing suicide
      rates.

PMID- 24669947
TI  - Mineralization of basalts in the CO2-H2O-SO2-O2 system.
AB  - Sequestering carbon dioxide (CO2) containing minor amounts of co-contaminants in
      geologic formations was investigated in the laboratory through the use of high
      pressure static experiments. Five different basalt samples were immersed in water
      equilibrated with supercritical CO2 containing 1 wt % sulfur dioxide (SO2) and 1
      wt % oxygen (O2) at reservoir conditions (~ 100 bar, 90  degrees C) for 48 and 98
      days. Gypsum (CaSO4) was a common precipitate, occurred early as elongated blades
      with striations, and served as substrates for other mineral products. In addition
      to gypsum, bimodal pulses of water released during dehydroxylation were key
      indicators, along with X-ray diffraction, for verifying the presence of jarosite
      alunite group minerals. Well-developed pseudocubic jarosite crystals formed
      surface coatings, and in some instances, mixtures of natrojarosite and
      natroalunite aggregated into spherically shaped structures measuring 100 MUm in
      diameter. Reaction products were also characterized using infrared spectroscopy,
      which indicated OH and Fe-O stretching modes. The presences of jarosite-alunite
      group minerals were found in the lower wavenumber region from 700 to 400 cm(-1).
      A strong preferential incorporation of Fe(III) into natrojarosite was attributed
      to the oxidation potential of O2. Evidence of CO2 was detected during thermal
      decomposition of precipitates, suggesting the onset of mineral carbonation.

PMID- 24669946
TI  - A ddRAD-based genetic map and its integration with the genome assembly of
      Japanese eel (Anguilla japonica) provides insights into genome evolution after
      the teleost-specific genome duplication.
AB  - BACKGROUND: Recent advancements in next-generation sequencing technology have
      enabled cost-effective sequencing of whole or partial genomes, permitting the
      discovery and characterization of molecular polymorphisms. Double-digest
      restriction-site associated DNA sequencing (ddRAD-seq) is a powerful and
      inexpensive approach to developing numerous single nucleotide polymorphism (SNP)
      markers and constructing a high-density genetic map. To enrich genomic resources
      for Japanese eel (Anguilla japonica), we constructed a ddRAD-based genetic map
      using an Ion Torrent Personal Genome Machine and anchored scaffolds of the
      current genome assembly to 19 linkage groups of the Japanese eel. Furthermore, we
      compared the Japanese eel genome with genomes of model fishes to infer the
      history of genome evolution after the teleost-specific genome duplication.
      RESULTS: We generated the ddRAD-based linkage map of the Japanese eel, where the
      maps for female and male spanned 1748.8 cM and 1294.5 cM, respectively, and were
      arranged into 19 linkage groups. A total of 2,672 SNP markers and 115 Simple
      Sequence Repeat markers provide anchor points to 1,252 scaffolds covering 151 Mb
      (13%) of the current genome assembly of the Japanese eel. Comparisons among the
      Japanese eel, medaka, zebrafish and spotted gar genomes showed highly conserved
      synteny among teleosts and revealed part of the eight major chromosomal
      rearrangement events that occurred soon after the teleost-specific genome
      duplication. CONCLUSIONS: The ddRAD-seq approach combined with the Ion Torrent
      Personal Genome Machine sequencing allowed us to conduct efficient and flexible
      SNP genotyping. The integration of the genetic map and the assembled sequence
      provides a valuable resource for fine mapping and positional cloning of
      quantitative trait loci associated with economically important traits and for
      investigating comparative genomics of the Japanese eel.

PMID- 24669948
TI  - Pulmonary lymphangitic carcinomatosis in liver carcinoma: a rare case report and
      literature review.
AB  - Primary liver carcinoma is the most important malignant disease. The nodular
      metastatic foci of liver carcinoma are usually found in the lung, adrenal gland
      or abdomen after resection or transplantation. Pulmonary lymphangitic
      carcinomatosis (PLC) accounts for approximately 6% to 8% of metastatic cancer in
      the lung. The occurrence of PLC is extremely rare in liver carcinoma. Herein we
      report the case of a patient with PLC after liver transplantation due to liver
      carcinoma. PLC was confirmed by clinical manifestations, imaging studies and
      cytologic examination of exfoliated cells in the pleural effusion. 

PMID- 24669949
TI  - Effects of one month treatment with propranolol and metoprolol on the relaxant
      and contractile function of isolated trachea from rats exposed to cigarette smoke
      for four months.
AB  - BACKGROUND AND OBJECTIVE: The effects of one-month treatment of beta-adrenergic
      receptor (AR) blockers on the relaxant function of airway in chronic obstructive
      pulmonary disease (COPD) are unknown. A passive cigarette smoking rat model was
      used to investigate the effect of beta-AR blockers. METHODS: Thirty-six rats were
      randomly divided into six groups: control (C); propranolol (P); metoprolol (M);
      smoking (S); smoking + propranolol (SP); and smoking + metoprolol (SM).
      Histological analysis of the lungs was done and isolated tracheal segments were
      studied in vitro to assess the contractile and relaxant function of the smooth
      muscle. The level of norepinephrine (NE) was measured. RESULTS: Airway
      inflammation was more severe in group S than group C (p < 0.001), and it was
      alleviated in group SP (p < 0.001) while had no change in group SM. After
      propranolol or metoprolol administration, the level of NE was significantly lower
      in both SP and SM groups (p < 0.01). The maximal contractile response to
      acetylcholine (Ach) in groups S and SM was increased compared to group C (p <
      0.01). Propranolol significantly inhibited contractile response in group SP (p <
      0.05), while metoprolol did not show the same effect. The curve of maximum
      relaxant rate to isoprenaline (Iso) shifted to the left in group SP (p < 0.01),
      while group SM showed no changes. CONCLUSION: One-month treatment with
      propranolol increased the relaxant effect mediated by the beta2-AR and decreased
      the contractile response to Ach by reducing the level of NE.

PMID- 24669950
TI  - Toxicological investigations on the respirable fraction of silicon carbide grain
      products by the in vitro vector model.
AB  - Increased lung cancer incidence with workers at the production site of crude
      silicon carbide (SiC) using the Acheson process has been reported. Several agents
      derived from the process were discussed as causative factors. Recently concern
      had been expressed about the presence of cleavage fragments (CFs) in commercial
      products fulfilling the WHO criteria for fibers. This study has focused on the
      toxicological significance of such CFs. The test samples were respirable
      fractions of five different commercial samples of SiC grains. The CF content
      (scanning electron microscopy) was in the range 17-493 fibers/ug. Crystalline
      silica and whiskers could not be detected. Quartz DQ12, cristobalite, SiC
      whisker, UICC crocidolite and electrocorundum were used as control reference
      samples. Biological activity was assessed with the in vitro vector model (VM) on
      ex vivo rat and guinea pig alveolar macrophages (AMs). The dose range of the VM
      is derived from calculated AM loads from intratracheal instillation experiments
      and confirmed by measured AM loads from inhalation studies on alumina monohydrate
      particles with low biological activity: <=120 pg/AM. The response of the
      references was clearly different from that of the SiC grains which yielded low
      toxicity overall. However, the parameter reactive oxygen species secreted by AMs
      was elevated at the higher SiC doses, but not related to the CF content of these
      samples. Our data showed that CFs seem to have no biological relevance. This is
      in agreement with results from recent studies in which no carcinogenic activity
      had been demonstrated for CFs.

PMID- 24669951
TI  - Biological effects of desert dust in respiratory epithelial cells and a murine
      model.
AB  - As a result of the challenge of recent dust storms to public health, we tested
      the postulate that desert dust collected in the southwestern United States
      imparts a biological effect in respiratory epithelial cells and an animal model.
      Two samples of surface sediment were collected from separate dust sources in
      northeastern Arizona. Analysis of the PM20 fraction demonstrated that the
      majority of both dust samples were quartz and clay minerals (total SiO2 of 52 and
      57%). Using respiratory epithelial and monocytic cell lines, the two desert dusts
      increased oxidant generation, measured by Amplex Red fluorescence, along with
      carbon black (a control particle), silica, and NIST 1649 (an ambient air
      pollution particle). Cell oxidant generation was greatest following exposures to
      silica and the desert dusts. Similarly, changes in RNA for superoxide dismutase
      1, heme oxygenase-1, and cyclooxygenase-2 were also greatest after silica and the
      desert dusts supporting an oxidative stress after cell exposure. Silica, desert
      dusts, and the ambient air pollution particle NIST 1649 demonstrated a capacity
      to activate the p38 and ERK1/2 pathways and release pro-inflammatory mediators.
      Mice, instilled with the same particles, showed the greatest lavage
      concentrations of pro-inflammatory mediators, neutrophils, and lung injury
      following silica and desert dusts. We conclude that, comparable to other
      particles, desert dusts have a capacity to (1) influence oxidative stress and
      release of pro-inflammatory mediators in respiratory epithelial cells and (2)
      provoke an inflammatory injury in the lower respiratory tract of an animal model.
      The biological effects of desert dusts approximated those of silica.

PMID- 24669952
TI  - Effect of the inactivation of lactate dehydrogenase, ethanol dehydrogenase, and
      phosphotransacetylase on 2,3-butanediol production in Klebsiella pneumoniae
      strain.
AB  - BACKGROUND: 2,3-Butanediol (2,3-BD) is a high-value chemical usually produced
      petrochemically but which can also be synthesized by some bacteria. To date,
      Klebsiella pneumoniae is the most powerful 2,3-BD producer which can utilize a
      wide range of substrates. However, many by-products are also produced by K.
      pneumoniae, such as ethanol, lactate, and acetate, which negatively regulate the
      2,3-BD yield and increase the costs of downstream separation and purification.
      RESULTS: In this study, we constructed K. pneumoniae mutants with lactate
      dehydrogenase (LDH), acetaldehyde dehydrogenase (ADH), and phosphotransacetylase
      (PTA) deletion individually by suicide vector conjugation.These mutants showed
      different behavior of production formation. Knock out of ldhA had little
      influence on the yield of 2,3-BD, whereas knock out of adhE or pta significantly
      improved the formation of 2,3-BD. The accumulation of the intermediate of 2,3-BD
      biosynthesis, acetoin, was decreased in all the mutants. The mutants were then
      tested in five different carbon sources and increased 2,3-BD was observed. Also a
      double mutant strain with deletion of adhE and ldhA was constructed which
      resulted in accelerated fermentation and higher 2,3-BD production. In fed-batch
      culture this strain achieved more than 100 g/L 2,3-BD from glucose with a
      relatively high yield of 0.49 g/g. CONCLUSION: 2,3-BD production was dramatically
      improved with the inactivation of adhE and pta. The inactivation of ldhA could
      advance faster cell growth and shorter fermentation time. The double mutant
      strain with deletion of adhE and ldhA resulted in accelerated fermentation and
      higher 2,3-BD production. These results provide new insights for industrial
      production of 2,3-BD by K. pneumoniae.

PMID- 24669953
TI  - First passage analysis of the folding of a beta-sheet miniprotein: is it more
      realistic than the standard equilibrium approach?
AB  - Simulations of first-passage folding of the antiparallel beta-sheet miniprotein
      beta3s, which has been intensively studied under equilibrium conditions by A.
      Caflisch and co-workers, show that the kinetics and dynamics are significantly
      different from those for equilibrium folding. Because the folding of a protein in
      a living system generally corresponds to the former (i.e., the folded protein is
      stable and unfolding is a rare event), the difference is of interest. In contrast
      to equilibrium folding, the Ch-curl conformations become very rare because they
      contain unfavorable parallel beta-strand arrangements, which are difficult to
      form dynamically due to the distant N- and C-terminal strands. At the same time,
      the formation of helical conformations becomes much easier (particularly in the
      early stage of folding) due to short-range contacts. The hydrodynamic
      descriptions of the folding reaction have also revealed that while the
      equilibrium flow field presented a collection of local vortices with closed
      "streamlines", the first-passage folding is characterized by a pronounced overall
      flow from the unfolded states to the native state. The flows through the locally
      stable structures Cs-or and Ns-or, which are conformationally close to the native
      state, are negligible due to detailed balance established between these
      structures and the native state. Although there are significant differences in
      the general picture of the folding process from the equilibrium and first-passage
      folding simulations, some aspects of the two are in agreement. The rate of
      transitions between the clusters of characteristic protein conformations in both
      cases decreases approximately exponentially with the distance between the
      clusters in the hydrogen bond distance space of collective variables, and the
      folding time distribution in the first-passage segments of the equilibrium
      trajectory is in good agreement with that for the first-passage folding
      simulations. 

PMID- 24669954
TI  - Pharmacokinetic and toxicological considerations for the treatment of diabetes in
      patients with liver disease.
AB  - INTRODUCTION: Patients with type 2 diabetes have an increased risk of chronic
      liver disease (CLD) such as non-alcoholic fatty liver disease and steatohepatitis
      and about one-third of cirrhotic patients have diabetes. However, the use of
      several antidiabetic agents may be a cause for concern in the case of hepatic
      impairment (HI). AREAS COVERED: An extensive literature search was performed to
      analyze the influence of HI on the pharmacokinetics (PK) of glucose-lowering
      agents and the potential consequences for clinical practice as far as the
      efficacy/safety balance of their use in diabetic patients with CLD is concerned.
      EXPERT OPINION: Almost no PK studies have been published regarding metformin,
      sulfonylureas, thiazolidinediones and alpha-glucosidase inhibitors in patients
      with HI. Only mild changes in PK of glinides, dipeptidyl peptidase-4 inhibitors
      and sodium glucose cotransporters type 2 inhibitors were observed in dedicated PK
      studies in patients with various degrees of HI, presumably without major clinical
      relevance although large clinical experience is lacking. Glucagon-like peptide-1
      receptor agonists have a renal excretion rather than liver metabolism. Rare
      anecdotal case reports of hepatotoxicity have been described with various glucose
      lowering agents contrasting with numerous reassuring data. Nevertheless, caution
      should be recommended, especially in patients with advanced cirrhosis, including
      with the use of metformin.

PMID- 24669955
TI  - Universal sulfide-assisted synthesis of M-Ag heterodimers (M = Pd, Au, Pt) as
      efficient platforms for fabricating metal-semiconductor heteronanostructures.
AB  - We report a universal sulfide-assisted synthesis strategy to prepare dumbbell
      like M-Ag heterodimers (M = Pd, Au, Pt). Sulfide ions can give fine control over
      the reaction kinetics of Ag precursors, resulting in the anisotropic overgrowth
      of Ag to realize the dumbbell-like heterodimers irrespective of the surface
      facets or components of the M domain. The M-Ag heterodimers were facilely
      transformed to M-Ag2S heterodimers via a simple sulfidation reaction. This study
      provides a versatile approach to realizing not only metal-metal heterodimers but
      also semiconductor-metal heterodimers and will pave the way for designing
      heteronanostructures with unprecedented morphologies and functions. 

PMID- 24669956
TI  - Challenge of managing sickle cell disease in a pediatric population living in
      kinshasa, democratic republic of congo: a sickle cell center experience.
AB  - In the Democratic Republic of Congo (DRC), sickle cell disease is not yet really
      regarded as a health care priority. The patterns of sickle cell disease in
      patients living in Kinshasa, DRC are discussed and the difficulties encountered
      in their management are highlighted. The cross-sectional survey is of sickle cell
      patients and their families attending the Centre de Medecine Mixte et d'Anemie SS
      de Yolo (CMMASS), Kinshasa, DRC, between January and April 2009. Completed
      questionnaires were received from 168 respondents (111 girls; 57 boys). Seventy
      one percent of the subjects were diagnosed before the age of 2 years but none in
      the neonatal period. Sickle cell disease was diagnosed in 54.8% of the patients
      after they had suffered pain crises. Of the 168 subjects, 74.0% had previously
      received blood transfusions. Seventy-five (45.0%) had more than three severe pain
      crises per year. A minority of 35.0% reported that they regularly took an
      antibioprophylaxis. Seventy-five (45.0%) subjects were eligible for hydroxyurea
      (HU) therapy but in all cases this drug was taken irregularly. Eighty-two percent
      of drugs were purchased by the parents. One hundred and sixty-three children
      (97.0%) were vaccinated according to the Expanded Programme on Immunization
      (EPI), 61.0% against Streptococcus pneumoniae and 16.0% against the Hepatitis B
      virus (HBV). No case of immunization against Hemophilus influenzae and Salmonella
      sp was reported. Neonatal screening programs, early educational detection
      programs for families, use of current method treatments and an implementation of
      a health insurance system for sickle cell disease will improve detection and
      management for these and future patients in our population.

PMID- 24669957
TI  - Mono- and bilayer WS2 light-emitting transistors.
AB  - We have realized ambipolar ionic liquid gated field-effect transistors based on
      WS2 mono- and bilayers, and investigated their opto-electronic response. A
      thorough characterization of the transport properties demonstrates the high
      quality of these devices for both electron and hole accumulation, which enables
      the quantitative determination of the band gap (Delta1L = 2.14 eV for monolayers
      and Delta2L = 1.82 eV for bilayers). It also enables the operation of the
      transistors in the ambipolar injection regime with electrons and holes injected
      simultaneously at the two opposite contacts of the devices in which we observe
      light emission from the FET channel. A quantitative analysis of the spectral
      properties of the emitted light, together with a comparison with the band gap
      values obtained from transport, show the internal consistency of our results and
      allow a quantitative estimate of the excitonic binding energies to be made. Our
      results demonstrate the power of ionic liquid gating in combination with
      nanoelectronic systems, as well as the compatibility of this technique with
      optical measurements on semiconducting transition metal dichalcogenides. These
      findings further open the way to the investigation of the optical properties of
      these systems in a carrier density range much broader than that explored until
      now. 

PMID- 24669958
TI  - Agonists for the adenosine A1 receptor with tunable residence time. A Case for
      nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines.
AB  - We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5
      cyano-2-thiopyrimidines as selective human adenosine A1 receptor (hA1AR) agonists
      with tunable binding kinetics, this without affecting their nanomolar affinity
      for the target receptor. They show a very diverse range of kinetic profiles (from
      1 min (compound 52) to 1 h (compound 43)), and their structure-affinity
      relationships (SAR) and structure-kinetics relationships (SKR) were established.
      When put in perspective with the increasing importance of binding kinetics in
      drug discovery, these results bring new evidence of the consequences of affinity
      only driven selection of drug candidates, that is, the potential elimination of
      slightly less active compounds that may display preferable binding kinetics. 

PMID- 24669959
TI  - Crystal structure of an engineered YopM-InlB hybrid protein.
AB  - BACKGROUND: The multi-domain protein InlB (internalin B) from Listeria
      monocytogenes is an agonist of the human receptor tyrosine kinase MET. Only the
      internalin domain directly interacts with MET. The internalin domain consists of
      seven central leucine-rich repeats (LRRs) flanked by an N-terminal helical cap
      domain and a C-terminal immunoglobulin-like structure. A potential function of
      the N-terminal cap in receptor binding could so far not be demonstrated by
      deleting the cap, since the cap is also implicated in nucleating folding of the
      LRR domain. RESULTS: We generated an InlB variant (YopM-InlB) in which the InlB
      cap domain was replaced by the unrelated N-terminal capping structure of the LRR
      protein YopM from Yersinia enterocolitica. The crystal structure of the
      engineered protein shows that it folds properly. Because the first LRR is
      structurally closely linked to the cap domain, we exchanged LRR1 along with the
      cap domain. This resulted in unexpected structural changes extending to LRR2 and
      LRR3, which are deeply involved in MET binding. As a consequence, the binding of
      YopM-InlB to MET was substantially weaker than that of wild type InlB. The
      engineered protein was about one order of magnitude less active in colony scatter
      assays than wild type InlB. CONCLUSIONS: We obtained a well-behaved InlB variant
      with an altered N-terminal capping structure through protein design. The reduced
      affinity for MET precludes a straightforward interpretation of the results from
      cell-based assays. Still, the engineered hybrid protein induced cell scatter,
      suggesting that the cap is required for folding and stability of InlB but is not
      essential for interactions that assemble the signalling-active receptor complex.
      The cap swap approach described here is clearly applicable to other L.
      monocytogenes internalins and other LRR proteins such as YopM and may yield
      useful structure/function correlates within this protein family.

PMID- 24669960
TI  - Does the sex of acute stroke patients influence the effectiveness of rt-PA?
AB  - BACKGROUND: Women have been reported to show more frequent recanalization and
      better recovery after intravenous (IV) recombinant tissue plasminogen activator
      (rt-PA) treatment for acute stroke compared with men. To investigate this we
      studied a series of stroke patients receiving IV rt-PA and undergoing acute
      transcranial doppler (TCD) examination. METHODS: Acute stroke patients received
      IV rt-PA and had acute TCD examination within 4 hours of symptom onset at 4 major
      stroke centers. TCD findings were interpreted using the Thrombolysis in Brain
      Ischemia (TIBI) flow grading system. The recanalization rates, and poor 3-month
      outcomes (modified Rankin scale >2) of men and women were compared using the chi
      square test. Multiple regression analysis was used to assess sex as a predictor
      of recanalization and poor 3-month outcome after controlling for age, baseline
      NIH Stroke Scale (NIHSS), time to treatment, hypertension, and blood glucose.
      RESULTS: 369 patients had TCD examinations before or during IV rt-PA treatment.
      The 199 (53.9%) men and 170 (46.1%) women had mean ages of 67 +/- 13 and 70 +/-
      14 years, respectively. The sexes did not differ significantly in baseline stroke
      severity, time to TCD examination, or time to thrombolysis. Of the men, 68
      (34.2%) had complete recanalization, 58 (29.1%) had partial recanalization, and
      73 (36.6%) had no recanalization. Of the women, 53 (31.2%) had complete
      recanalization, 46 (27%) had partial recanalization, and 71 (41.8%) had no
      recanalization (p = 0.6). Multiple regression analyses showed no difference
      between the sexes in recanalization rate, time to recanalization, or clinical
      outcome at 3 months. CONCLUSIONS: In our study; sex is not a significant
      predictor of recanalization rate, time to recanalization or 3-month outcome in
      stroke patients following IV rt-PA. TRIAL REGISTRATION: Data from CLOTBUST trial
      Clinicaltrials.gov Identifier: NCT01240356.

PMID- 24669961
TI  - Effects of vitamin D supplementation on alveolar macrophage gene expression:
      preliminary results of a randomized, controlled trial.
AB  - BACKGROUND: Vitamin D deficiency has been implicated as a factor in a number of
      infectious and inflammatory lung diseases. In the lung, alveolar macrophages play
      a key role in inflammation and defense of infection, but there are little data
      exploring the immunomodulatory effects of vitamin D on innate lung immunity in
      humans. The objective of this study was to determine the effects of vitamin D
      supplementation on gene expression of alveolar macrophages. METHODS: We performed
      a parallel, double-blind, placebo-controlled, randomized trial to determine the
      effects of vitamin D on alveolar macrophage gene expression. Vitamin D3 (1000
      international units/day) or placebo was administered to adults for three months.
      Bronchoscopy was performed pre- and post-intervention to obtain alveolar
      macrophages. Messenger RNA was isolated from the macrophages and subjected to
      whole genome exon array analysis. The primary outcome was differential gene
      expression of the alveolar macrophage in response to vitamin D supplementation.
      Specific genes underwent validation by polymerase chain reaction methods.
      RESULTS: Fifty-eight subjects were randomized to vitamin D (n = 28) or placebo (n
      = 30). There was a marginal overall difference between treatment group and
      placebo group in the change of 25-hydroxyvitaminD levels (4.43 ng/ml vs. 0.2
      ng/ml, p = 0.10). Whole genome exon array analysis revealed differential gene
      expression associated with change in serum vitamin D levels in the treated group.
      CCL8/MCP-2 was the top-regulated cytokine gene and was further validated.
      CONCLUSIONS: Although only a non-significant increased trend was seen in serum
      vitamin D levels, subjects treated with vitamin D supplementation had immune
      related differential gene expression in alveolar macrophages. TRIAL REGISTRATION:
      ClinicalTrials.org: NCT01967628.

PMID- 24669962
TI  - Symptoms of myocardial infarction: concordance between paramedic and hospital
      records.
AB  - INTRODUCTION: To further reduce time to definitive therapy for acute myocardial
      infarction (MI) patients, the focus of research needs to be on better
      understanding prehospital delay in recognition and response to symptoms.
      Paramedic clinical records can serve as a convenient source of data for such
      studies, but their accuracy needs to be established. OBJECTIVES: This study aimed
      to determine the concordance of the symptoms and symptom-onset time recorded in
      the paramedic patient care record (PCR) with those recorded in the hospital
      medical record for MI patients. METHODS: A retrospective review of paramedic and
      hospital medical records was undertaken between January 1, 2008 and October 31,
      2009 for all patients with an emergency department (ED) discharge diagnosis of MI
      at a single teaching hospital in Perth, Western Australia. The symptoms of MI and
      onset times documented in the paramedic PCR were compared with those recorded in
      the hospital medical record, which was considered the "gold standard." The study
      assessed differences in documentation using McNemar's tests, and concordance was
      described by kappa and adjusted kappa statistics, sensitivity, specificity, and
      positive and negative predictive value (PPV, NPV). RESULTS: Of 810 patients with
      an ED discharge diagnosis of MI, 584 (71%) patients arrived by ambulance and 509
      patients had a paramedic PCR. After exclusions, 400 patients had both paramedic
      PCR and hospital medical records available for review. Of 21 documented MI
      symptoms, the majority (71.4%) had adjusted kappa statistics greater than 0.75,
      and observed agreement greater than 90%. For the symptom of chest pain,
      sensitivity, specificity, PPV, and NPV were all over 85%. Where recorded in both
      records (n = 196, 49%) the symptom-onset time agreed exactly for 118 (60.2%)
      records, differed by 1-15 minutes for 24 (12.2%) records, and differed by 16-30
      minutes for 22 (11.2%) records. CONCLUSION: Our study demonstrated that
      documentation of the common symptoms of MI and symptom-onset time was similar
      between the paramedic and hospital records, justifying the use of paramedic PCRs
      as a source of data for research in prehospital MI patient delay. Further
      research is required to investigate why symptom-onset time was not routinely
      documented for all patients with chest pain.

PMID- 24669963
TI  - The N-terminal extension of betaB1-crystallin chaperones beta-crystallin folding
      and cooperates with alphaA-crystallin.
AB  - beta/gamma-Crystallins are the major structural proteins in mammalian lens. The N
      terminal truncation of betaB1-crystallin has been associated with the regulation
      of beta-crystallin size distributions in human lens. Herein we studied the roles
      of betaB1 N-terminal extension in protein structure and folding by constructing
      five N-terminal truncated forms. The truncations did not affect the secondary and
      tertiary structures of the main body as well as stability against denaturation.
      Truncations with more than 28 residues off the N-terminus promoted the
      dissociation of the dimeric betaB1 into monomers in diluted solutions.
      Interestingly, the N-terminal extension facilitated betaB1 to adopt the correct
      folding pathway, while truncated proteins were prone to undergo the
      misfolding/aggregation pathway during kinetic refolding. The N-terminal extension
      of betaB1 acted as an intramolecular chaperone (IMC) to regulate the kinetic
      partitioning between folding and misfolding. The IMC function of the N-terminal
      extension was also critical to the correct refolding of beta-crystallin heteromer
      and the action of the lens-specific molecular chaperone alphaA-crystallin. The
      cooperation between IMC and molecular chaperones produced a much stronger
      chaperoning effect than if they acted separately. To our knowledge, this is the
      first report showing the cooperation between IMC and molecular chaperones. 

PMID- 24669964
TI  - Cytological smears and cell blocks on endobronchial aspirates complement each
      other and allow a higher diagnostic yield.
AB  - The accurate diagnosis of lung carcinoma has become compulsory especially after
      the introduction of new target therapies. Most of the patients are non operable.
      This fact points out the diagnostic importance of the cytology specimen. Our
      target was to assess the diagnostic efficacy of bronchial smears and cell blocks
      by comparing their results with those of the final diagnoses made on biopsies. We
      conducted a prospective study of 55 bronchial aspirates. It showed a sensitivity
      of 100% and a specificity of 100% when coupling both techniques. These results
      put emphasis on the diagnostic efficacy of both bronchial smears and cell blocks
      in diagnosing bronchial carcinoma. 

PMID- 24669965
TI  - Risk factors and their impact on carotid intima-media thickness in young and
      middle-aged ischemic stroke patients and controls: the Norwegian Stroke in the
      Young Study.
AB  - BACKGROUND: Vascular morbidity and mortality due to cardiovascular disease (CVD)
      are high after ischemic stroke at a young age. Data on carotid intima-media
      thickness (cIMT) as marker of atherosclerosis are scarce for young stroke
      populations. In this prospective case-control study, we examined cIMT, the burden
      of vascular risk factors (RF) and their associations among young and middle-aged
      ischemic stroke patients and controls. We aimed to detect clinical and sub
      clinical arterial disease. METHODS: This study was conducted in 150 patients aged
      15-60 years and 84 controls free of CVD. We related RF to ultrasonographic B-mode
      cIMT-measurements obtained from 12 standardized multiangle measurements in the
      common carotid artery (CCA), carotid bifurcation (BIF) and internal carotid
      artery (ICA). RESULTS: RF burden was higher among patients than among controls (p
      < 0.001). In multivariate analyses of all 234 participants, increased cIMT was
      associated with age in each carotid segment. Incident stroke was associated with
      increased ICA-IMT. ICA-IMT increase was associated with a family history of CVD
      among patients aged 15-44 years, and with RF at mid-age. The overall cIMT
      difference between patients and controls was 12% for CCA, 17% for BIF and 29% for
      ICA. Further, increased CCA-IMT was associated with male sex and hypertension.
      Increased BIF-IMT was associated with dyslipidemia, coronary heart disease and
      smoking. Increased ICA-IMT was associated with dyslipidemia and stroke.
      CONCLUSIONS: Ischemic stroke is associated with increased ICA-IMT, related to a
      family history of CVD among patients aged <45 years, and to increasing RF burden
      with increasing age. Preventive strategies and aggressive RF treatment are
      indicated to avoid future cardiovascular events. TRIAL REGISTRATION: NOR-SYS is
      registered in ClinicalTrials.gov (NCT01597453).

PMID- 24669967
TI  - Computational evaluation of the dynamic fluctuations of peripheral loops
      enclosing the catalytic tunnel of a family 7 cellobiohydrolase.
AB  - The size and character of the peripheral loops enclosing the active site for
      cellulase enzymes is believed to play a major role in dictating many critical
      enzymatic properties. For many cellulases it is observed that fully enclosed
      active sites forming a tunnel are more conducive to cellobiohydrolase activity
      and the ability to processively move along the substrate. Conversely, a more open
      active site groove is indicative of endoglucanase activity. For both
      cellobiohydrolases and endoglucanases, the loop regions have been implicated in
      the ability of the enzyme to bind substrate, influence the pKa of active site
      residues, modulate the catalytic activity, and influence thermal stability.
      Reported here are constant pH molecular dynamics (CpHMD) simulations that
      investigate the role of dynamic fluctuations, substrate interactions, and residue
      pKa values for the peripheral loops enclosing the active site of the
      cellobiohydrolase Melanocarpus albomyces Cel7B. Two highly flexible loop regions
      in the free enzyme have been identified, which impact the overall dynamical
      motions of the enzyme. Charge interactions between Asp198 and Asp367, which
      reside on two adjacent loops, were found to influence the overall loop
      conformations and dynamics. In the presence of a substrate the protonation of
      Asp367, Asp198, and Tyr370 were found to stabilize substrate binding and control
      the movement of two peripheral loops onto the active site containing the
      substrate (i.e., clamping down). The substrate-induced response of the loop
      regions secures the cellulose polymer in the catalytic tunnel and creates an
      environment that is conducive to hydrolysis of the glycosidic bond. 

PMID- 24669968
TI  - Editorial: Perioperative organoprotection, something new and something wrong.

PMID- 24669966
TI  - Global gene expression in endometrium of high and low fertility heifers during
      the mid-luteal phase of the estrous cycle.
AB  - BACKGROUND: In both beef and dairy cattle, the majority of early embryo loss
      occurs within the first 14 days following insemination. During this time-period,
      embryos are completely dependent on their maternal uterine environment for
      development, growth and ultimately survival, therefore an optimum uterine
      environment is critical to their survival. The objective of this study was to
      investigate whether differences in endometrial gene expression during the mid
      luteal phase of the estrous cycle exist between crossbred beef heifers ranked as
      either high (HF) or low fertility (LF) (following four rounds of artificial
      insemination (AI)) using the Affymetrix(r) 23 K Bovine Gene Chip. RESULTS:
      Conception rates for each of the four rounds of AI were within a normal range: 70
      73.3%. Microarray analysis of endometrial tissue collected on day 7 of the
      estrous cycle detected 419 differentially expressed genes (DEG) between HF (n =
      6) and LF (n = 6) animals. The main gene pathways affected were, cellular growth
      and proliferation, angiogenesis, lipid metabolism, cellular and tissue morphology
      and development, inflammation and metabolic exchange. DEG included, FST, SLC45A2,
      MMP19, FADS1 and GALNT6. CONCLUSIONS: This study highlights, some of the
      molecular mechanisms potentially controlling uterine endometrial function during
      the mid-luteal phase of the estrous cycle, which may contribute to uterine
      endometrial mediated impaired fertility in cattle. Differentially expressed genes
      are potential candidate genes for the identification of genetic variation
      influencing cow fertility, which may be incorporated into future breeding
      programmes.

PMID- 24669969
TI  - Preoperative levosimendan. A new way for organoprotection.
AB  - Preoperative use of levosimendan in cardiac surgery patients is one of the most
      attractive therapeutic alternatives in subjects with left or right ventricular
      dysfunction. Our review explores the pharmacological bases and clinical evidence
      for the use of levosimendan, with the intention of making a series of
      recommendations regarding its use in preoperative optimization prior to cardiac
      surgery. We carried out a survey of 102 Spanish anesthesiologists in order to
      shed light on the grey areas regarding the use of this drug prior to surgery. Our
      findings suggest that levosimendan is recommended for patients with severe left
      or right ventricular dysfunction, moderate left ventricular dysfunction in which
      Intra-aortic Balloon Counterpulsation (IABC) is necessary and severe pulmonary
      hypertension. Administration of levosimendan prior to surgical cardiac
      intervention without an initial bolus reduces the likelihood of complications. 

PMID- 24669970
TI  - Is time to change to halogenated drugs in cardiac surgery, what do we have to do
      with propofol?
AB  - There is initial evidence, at least in cardiac surgery, that total intra-venous
      anesthesia (usually a propofol-based total intravenous anesthesia) is associated
      with an increased mortality when compared to an anesthetic plan including a
      halogenated anesthetics. The cardiac protective properties of halogenated agents
      (desflurane, isoflurane and sevoflurane) have not been confirmed in non-cardiac
      surgery and mixed results exist for patients admitted in postoperative intensive
      care units. This article summarizes the papers with the most impressive findings
      in favor of halogenated anesthetics, but it recognizes that, at the same time,
      there is no evidence based medicine against the use of propofol, highlighting the
      need for large randomized trials that should focus on survival. 

PMID- 24669971
TI  - Pharmacological strategies for the prevention of acute kidney injury following
      cardiac surgery: an overview of systematic reviews.
AB  - CONTEXT: Post cardiac surgery acute kidney injury (AKI) is common, poorly
      understood and associated with a significant increase in morbidity and mortality.
      OBJECTIVES: An overview of systematic reviews that have evaluated pharmacological
      agents for the prevention of AKI post cardiac surgery. DATA SOURCES: We searched
      electronic databases (PubMed and the Cochrane Database of Systematic Reviews)
      from inception to January 2014. STUDY SELECTION: Systematic reviews of randomized
      controlled trials that have evaluated pharmacological agents for the prevention
      of AKI in adult patients undergoing cardiac surgery. DATA ANALYSIS: Numbers
      needed to treat (NNT) or harm (NNH) were calculated from pooled events given in
      each meta-analysis. Primary outcome measures were defined as (i) mortality, (ii)
      need for renal replacement therapy (RRT), and (iii) acute kidney injury. RESULTS:
      Data from 7 systematic reviews evaluating 6 different pharmacological
      renoprotective agents were included. Dopamine, fenoldopam and N-acetylcysteine
      did not demonstrate any benefit in terms of mortality, need for RRT or incidence
      of AKI. Atrial natriuretic peptide reduced the need for RRT (NNT = 22 (95% CI: 13
      to 73) and brain natriuretic peptide reduced the incidence of AKI (NNT = 11 (95%
      CI: 6 to 32), although both agents did not demonstrate any effect on mortality.
      Loop diuretics demonstrated increased incidence of AKI (NNH = 8 (95% CI: 5 to
      15). CONCLUSION: There is a paucity of effective renoprotective agents that can
      be used in adult cardiac surgical patients. There is an urgent need to develop
      novel renoprotective strategies.

PMID- 24669972
TI  - Neuroprotective effects of intravenous anesthetics: a new critical perspective.
AB  - Perioperative cerebral damage can result in various clinical sequela ranging from
      minor neurocognitive deficits to catastrophic neurological morbidity with
      permanent impairment and death. The goal of neuroprotective treatments is to
      reduce the clinical effects of cerebral damage through two major mechanisms:
      increased tolerance of neurological tissue to ischemia and changes in intra
      cellular responses to energy supply deprivation. In this review, we present the
      clinical evidence of intravenous anesthetics on perioperative neuroprotection,
      and we also provide a critical perspective for future studies. The
      neuroprotective efficacy of the intravenous anesthetics thiopental, propofol and
      etomidate is unproven. Lidocaine may be neuroprotective in non-diabetic patients
      who have undergoing cardiac surgery with cardiopulmonary bypass (CBP) or with a
      48-hour infusion, but conclusive data are lacking. There are several limitations
      of clinical studies that evaluate postoperative cognitive dysfunction (POCD),
      including difficulties in identifying patients at high-risk and a lack of
      consensus for defining the "gold-standard" neuropsychological testing. Although a
      battery of neurocognitive tests remains the primary method for diagnosing POCD,
      recent evidence suggests a role for novel biomarkers and neuroimaging to
      preemptively identify patients more susceptible to cognitive decline in the
      perioperative period. Current evidence, while inconclusive, suggest that
      intravenous anesthetics may be both neuroprotective and neurotoxic in the
      perioperative period. A critical analysis on data recorded from randomized
      control trials (RCTs) is essential in identifying patients who may benefit or be
      harmed by a particular anesthetic. RCTs will also contribute to defining
      methodologies for future studies on the neuroprotective effects of intravenous
      anesthetics.

PMID- 24669973
TI  - The effects of sevoflurane or remifentanil on the stress response to surgical
      stimulus.
AB  - Tissue injury secondary to surgical lesion produces profound changes in endocrine
      metabolic function and defence mechanisms in the patient (inflammatory,
      immunological), leading to an increase in catabolism, immunosuppression and
      postoperative morbidity. The best anaesthetic and surgical technique should be
      capable of modulating this response, especially in major surgery, where it can be
      most harmful and increase patient morbidity. Many of the changes that maintain
      homeostasis are controlled by the hypothalamicpituitary- adrenal axis. The
      autonomic-adrenal response is usually immediate, compared to the hypothalamus
      pituitary gland, which is slower and longer lasting. Cytokine synthesis and
      release are the earliest stages in the response to tissue lesion. The most
      frequently studied cytokines in surgical stress response are IL-6 and TNF-alpha.
      Inflammatory mediator concentrations are direct indicators of perioperative
      stress, while haemodynamic changes are considered the indirect indicators of this
      response. Multiple anaesthetic techniques have been described to modify the
      stress response in patients undergoing elective surgery. The aim of this review
      is to present clinical evidence on perioperative stress modulation with different
      anesthetics. We also describe a different point of view in immunomodulation with
      the intraoperative management of haemodynamic responses with inhalational bolus
      of sevoflurane or with remifentanil intravenous bolus. The effects of sevoflurane
      used as an inhalational bolus to counteract patients' intraoperative haemodynamic
      responses modulates the immune response the same than opioid remifentanil.

PMID- 24669974
TI  - Effects of remifentanil on the cardiac conduction system. Our experience in the
      study of remifentanil electrophysiological properties.
AB  - Remifentanil is a selective mu-opioid receptor agonist characterized by a rapid
      onset and ultrashort predictable duration of action providing intense analgesia
      without prolonged respiratory depression. Remifentanil has been implicated in the
      causation of intraoperative bradyarrhythmias and asystole both in adults and in
      pediatric patients. Electrophysiological studies in humans and animals show that
      remifentanil provokes a dose-dependent depressor effect on sinus and AV node
      function, manifested by a significant prolongation of sinus node recovery time,
      sino-atrial conduction time and Wenckebach cycle length. These electrophysiologic
      effects of remifentanil suggest that it should be used with attention in
      vulnerable patients with predisposition to bradiarritmias during anesthesia. 

PMID- 24669975
TI  - Mucoadhesive elementary osmotic pump tablets of trimetazidine for controlled drug
      delivery and reduced variability in oral bioavailability.
AB  - The objectives of this work was preparation and evaluation of the mucoadhesive
      elementary osmotic pump tablets of trimetazidine hydrochloride to achieve desired
      controlled release action and augmentation of oral drug absorption. The drug
      loaded core tablets were prepared employing the suitable tableting excipients and
      coated with polymeric blend of ethyl cellulose and hydroxypropyl
      methylethylcellulose E5 (4:1). The prepared tablets were characterized for
      various quality control tests and in vitro drug release. Evaluation of drug
      release kinetics through model fitting suggested the Fickian mechanism of drug
      release, which was regulated by osmosis and diffusion as the predominant
      mechanism. Evaluation of mucoadhesion property using texture analyzer suggested
      good mucoadhesion potential of the developed osmotic systems. Solid state
      characterization using Fourier-transform infrared spectroscopy, differential
      scanning calorimetry and powder X-ray diffraction spectroscopy confirmed the
      absence of any physiochemical incompatibilities between drug and excipients.
      Scanning electron microscopy analysis showed the smooth surface appearance of the
      coated tablets with intact polymeric membrane without any fracture. In vivo
      pharmacokinetic studies in rabbits revealed 3.01-fold enhancement in the oral
      bioavailability vis-a-vis the marketed formulation (Vastarel MR(r)). These
      studies successfully demonstrate the bioavailability enhancement potential of the
      mucoadhesive elementary osmotic pumps as novel therapeutic systems for other
      drugs too. 

PMID- 24669976
TI  - Nanovesicular carrier-mediated transdermal delivery of tadalafil: i-formulation
      and physicsochemical characterization.
AB  - The limited permeability of stratum corneum, the main skin barrier, towards
      pharmaceutical active ingredients represents the main obstacle encounter the
      transdermal drug delivery system. In the current study, penetration enhancer
      containing nanoliposomes, that is, penetrosomes were formulated incorporating
      tadalafil to enhance its transdermal permeability. Hydration-sonication method
      was used to prepared penetrosomes bearing tadalafil. The prepared nanocarriers
      were characterized in terms of vesicles shape and surface morphology, size and
      size distribution, zeta potential, entrapment efficiency, and elasticity. Results
      pointed to that penetrosomes were spherical in shape with a unilamellar-closed
      structure in the nanometric narrow size range proved by their law span index.
      Penetrosomes formulations elaborated deformable vesicles more than the
      conventional liposomes, with the Penetrosomes-based Labrasol(r) being the most
      deformable formulation. Penetrosomes-ultraelastic nanoliposomes represent an
      attractive vehicle for transdermal delivery of tadalafil to treat erectile
      dysfunction. 

PMID- 24669977
TI  - Co-administration with cell penetrating peptide enhances the oral bioavailability
      of docetaxel-loaded nanoparticles.
AB  - This study proposes a novel docetaxel (DTX) cyclodextrin inclusion-loaded poly
      (lactic-co-glycolic acid) (PLGA) nanoparticles (D-CNPs) system with cell
      penetrating peptide (CPP), and evaluates its potential for oral administration of
      DTX. Heptaarginine (R7) was used as the CPP. D-CNPs were prepared by the double
      emulsification method. The mean particle size and zeta potential of the resulting
      D-CNPs were 198.7 +/- 12.56 nm and -27.25 +/- 4.62 mV, respectively, and their
      mean encapsulation efficiency and drug loading were 80.35 +/- 6.37% and 1.02 +/-
      0.15%, respectively. The morphology of the D-CNPs was observed by scanning
      electron microscope (SEM) and transmission electron microscope (TEM). The release
      behavior of the D-CNPs was studied by using the dialysis method. The relative
      bioavailability of D-CNPs and D-CNPs co-administered with R7 was enhanced about
      5.57- and 9.43-fold, respectively, compared with the free DTX suspension.
      Furthermore, D-CNPs with R7 displayed maximum cytotoxicity against MCF-7 cells in
      MTT assay. D-CNPs co-administered with R7 showed markedly higher fluorescence
      intensity than D-CNPs without CPP. The results suggest that the D-CNPs co
      administered with R7 could be a potential delivery system with excellent
      therapeutic efficacy for targeting the drugs to cancer cells. 

PMID- 24669978
TI  - Enhanced dissolution and bioavailability of grapefruit flavonoid Naringenin by
      solid dispersion utilizing fourth generation carrier.
AB  - CONTEXT: Naringenin (NRG), the aglycone flavonoid present in grapefruits,
      possesses anti-inflammatory, anti-carcinogenic, anti-lipid peroxidation and
      hepato-protective effects. However, it is poorly soluble in water and exhibits
      slow dissolution after oral ingestion, thus restricting its therapeutic efficacy.
      OBJECTIVE: With the aim to enhance the dissolution rate and oral bioavailability
      of NRG, solid dispersion technique has been applied using Soluplus(r) as carrier.
      METHODS: Solid dispersions of NRG were prepared by solvent evaporation and
      kneading methods using various ratios (1:4, 3:7, 2:3 and 1:1) of NRG:Carrier.
      Characterization of the optimized formulations was performed using Fourier
      transform infrared spectroscopy, differential scanning calorimetry (DSC) and X
      ray diffraction (XRD) analysis. The in vivo behavior of the optimized
      formulations was also investigated in Wistar Albino rats. RESULTS: NRG solid
      dispersion showed a significantly higher solubility and drug dissolution rate
      than pure NRG (p < 0.001) and it followed the Higuchi model. Among the different
      methods employed for the preparation of solid dispersions, solvent evaporation
      showed better drug release profile. DSC analysis indicated reduced crystallinity
      of NRG as no discrete peaks of NRG were observed. This was further substantiated
      by XRD analysis. Furthermore, area under the drug concentration time-curve (AUC)
      of NRG from solid dispersion revealed a significant increase in NRG absorption
      compared to NRG alone. CONCLUSION: Based on these results, it was concluded that
      solid dispersion technique markedly enhances the in vitro drug release and in
      vivo behavior of the grapefruit flavonoid NRG.

PMID- 24669979
TI  - Muscarinic receptor antagonists for the treatment of chronic obstructive
      pulmonary disease.
AB  - INTRODUCTION: Long-acting muscarinic receptor antagonists (LAMAs) are central to
      the treatment of chronic obstructive pulmonary disease (COPD) because of the
      important role of the cholinergic system in the pathophysiology of this disorder.
      AREAS COVERED: LAMAs show clinically meaningful effects in lung function and
      other important supportive outcomes, such as exacerbations, health-related
      quality of life, dyspnea, rescue medication use and nighttime/early morning
      symptoms, and are safe. Muscarinic receptor antagonists could exert other useful
      actions such as the anti-inflammatory, anti-remodeling, mucus-modifying, and anti
      cough effects. Concerns have been raised about possible associations of
      muscarinic receptor antagonists with cardiovascular morbidity and mortality.
      Muscarinic receptor antagonists can be combined with long-acting beta2-agonists
      (LABAs), inhaled corticosteroids (ICSs) and LABA + ICS. There are number of LAMAs
      that are being identified but only few have reached the clinical development.
      Fixed-dose combination formulations of both novel and established LAMAs with
      LABAs are being developed. EXPERT OPINION: There are important questions
      concerning the use of LAMAs in the treatment of patients suffering from stable
      COPD that need conclusive answers.

PMID- 24669980
TI  - Notification card to alert for methicillin-resistant Staphylococcus aureus is
      stigmatizing from the patient's point of view.
AB  - BACKGROUND: The importance of alerting health care systems of patients carrying
      multidrug-resistant bacteria (MRB) is highlighted in numerous guidelines. In the
      absence of electronic alert systems, notification cards are often recommended,
      but have rarely been evaluated. We evaluated patient experiences of receiving and
      using a methicillin-resistant Staphylococcus aureus (MRSA) notification card.
      METHODS: Two cohorts of patients given a card when identified for the first time
      as a carrier in 1999-2003 and 2008-2010, responded to questionnaires distributed
      in 2004 and 2011, respectively. The response rate in 2004 was 92 (38 females)/129
      and in 2011 was 110 (55 females)/209. In addition, 63% and 49%, respectively,
      followed the encouragement to provide written comments to the questions. These
      were analysed using a qualitative method. RESULTS: The patients took
      responsibility not to infect others, reported high usage, and acknowledged the
      importance of the card to inform health care institutions about their carrier
      status, despite experiencing fear, disrespect, lack of knowledge, and
      unprofessional behaviour when presenting it to personnel. Alarmingly these
      stigmatizing experiences were more frequent in 2011. Professional behaviour was
      reported from the infectious disease clinic. A majority of the patients were
      unaware of how they had acquired MRSA. CONCLUSIONS: The MRSA notification card
      was felt to stigmatize the patient, which makes its use questionable. Other alert
      methods need to be developed. Most importantly, the study demonstrates the
      importance for these patients to meet staff educated about MRB. Thus, there is an
      urgent need to educate health care professionals at all levels.

PMID- 24669981
TI  - A functionally stable manganese oxide oxygen evolution catalyst in acid.
AB  - First-row metals have been a target for the development of oxygen evolution
      reaction (OER) catalysts because they comprise noncritical elements. We now
      report a comprehensive electrochemical characterization of manganese oxide (MnOx)
      over a wide pH range, and establish MnOx as a functionally stable OER catalyst
      owing to self-healing, is derived from MnOx redeposition that offsets catalyst
      dissolution during turnover. To study this process in detail, the oxygen
      evolution mechanism of MnOx was investigated electrokinetically over a pH range
      spanning acidic, neutral, and alkaline conditions. In the alkaline pH regime, a
      ~60 mV/decade Tafel slope and inverse first-order dependence on proton
      concentration were observed, whereas the OER acidic pH regime exhibited a quasi
      infinite Tafel slope and zeroth-order dependence on proton concentration. The
      results reflect two competing mechanisms: a one-electron one-proton PCET pathway
      that is dominant under alkaline conditions and a Mn(3+) disproportionation
      process, which predominates under acidic conditions. Reconciling the rate laws of
      these two OER pathways with that of MnOx electrodeposition elucidates the self
      healing characteristics of these catalyst films. The intersection of the kinetic
      profile of deposition and that of water oxidation as a function of pH defines the
      region of kinetic stability for MnOx and importantly establishes that a non-noble
      metal oxide OER catalyst may be operated in acid by exploiting a self-healing
      process. 

PMID- 24669982
TI  - Consumer perceptions of the Nutrition Facts table and front-of-pack nutrition
      rating systems.
AB  - Preferences for, and consumer friendliness of, front-of-pack (FOP) nutrition
      rating systems have not been studied in a Canadian population, and studies
      comparing systems that are accompanied by mandatory labelling, such as Canada's
      Nutrition Facts table (NFt), are lacking. The purpose of this study was to
      evaluate 4 FOP systems relative to the NFt with respect to consumer friendliness
      and their influence on perceptions of the healthiness and nutrient content of
      food. Canadian consumers (n = 3029) participating in an online survey were
      randomized to score the consumer friendliness of 1 of 5 FOP conditions with or
      without an NFt and to score the healthiness and nutrient content of 2 foods using
      the provided label(s). The mean differences in scores were evaluated with
      analysis of covariance (ANCOVA) controlling for age, gender, and education, with
      Tukey-Kramer adjustments for multiple comparisons. The NFt received the highest
      scores of consumer friendliness with respect to liking, helpfulness, credibility,
      and influence on purchase decisions (p < 0.05); however, consumers still
      supported the implementation of a single, standardized FOP system, with the
      nutrient-specific systems (a "Traffic Light" and a Nutrition Facts FOP system)
      being preferred and scored as more consumer friendly than the summary indicator
      systems. Without the NFt, consumer ratings of the healthiness and calorie and
      nutrient content differed by FOP system. With the NFt present, consumers rated
      the healthiness and calorie and nutrient content similarly, except for those who
      saw the Traffic Light; their ratings were influenced by the Traffic Light's
      colours. The introduction of a single, standard, nutrient-specific FOP system to
      supplement the mandatory NFt should be considered by Canadian policy makers. 

PMID- 24669983
TI  - Effect of head-out water immersion on vascular function in healthy subjects.
AB  - Immersion in thermoneutral water increases cardiac output and peripheral blood
      flow and reduces systemic vascular resistance. This study examined the effects of
      head-out water immersion on vascular function. Twelve healthy middle-aged males
      were immersed during 60 min in the seated position, with water at the level of
      xiphoid. Local and central vascular tone regulating systems were studied during
      that time. Brachial artery diameter and blood flow were recorded using
      ultrasonography and Doppler. Endothelial function was assessed with flow-mediated
      dilation. Results were compared with the same investigations performed under
      reference conditions in ambient air. During water immersion, brachial artery
      diameter increased (3.7 +/- 0.2 mm in ambient air vs. 4 +/- 0.2 mm in water
      immersion; p < 0.05). Endothelium-mediated dilation was significantly lower in
      water immersion than in ambient air (10% vs. 15%; p = 0.01). Nevertheless, the
      difference disappeared when the percentage vasodilatation of the brachial artery
      was normalized to the shear stimulus. Smooth muscle-mediated dilation was similar
      in the 2 conditions. Spectral analysis of systolic blood pressure variability
      indicated a decrease in sympathetic vascular activity. Plasma levels of nitric
      oxide metabolites remained unchanged, whereas levels of natriuretic peptides were
      significantly elevated. An increase in brachial blood flow, a decrease in
      sympathetic activity, a warming of the skin, and an increase in natriuretic
      peptides might be involved in the increase in reference diameter observed during
      water immersion. Endothelial cell reactivity and smooth muscle function did not
      appear to be altered. 

PMID- 24669985
TI  - Muscle metabolism during fatiguing isometric quadriceps exercise in adolescents
      and adults.
AB  - Children and adolescents are less susceptible to muscle fatigue during repeated
      bouts of high-intensity exercise than adults, but the physiological basis for
      these differences is not clear. The purpose of the current investigation was to
      investigate the muscle metabolic responses, using 31-phosphorus magnetic
      resonance spectroscopy, during fatiguing isometric quadriceps exercise in 13
      adolescents (7 females) and 14 adults (8 females). Participants completed 30
      maximal voluntary contractions (6-s duration) separated by 6 s of rest. Fatigue
      was quantified as the relative decrease in force over the test. Fatigue was not
      significantly different with age (p = 0.20) or sex (p = 0.63). Metabolic
      perturbation (change in phosphocreatine, inorganic phosphate, and ADP
      concentrations) was significantly greater in adults compared with adolescents; no
      sex effects were present. Muscle pH did not differ with age or sex.
      Phosphocreatine recovery following exercise was not significantly different with
      age (p = 0.27) or sex (p = 0.97) but a significant interaction effect was present
      (p = 0.04). Recovery tended to be faster in boys than men but slower in girls
      than women, though no significant group differences were identified. The results
      of this study show that at a comparable level of muscle fatigue, the metabolic
      profile is profoundly different between adolescents and adults. 

PMID- 24669984
TI  - Biochemical impact of soccer: an analysis of hormonal, muscle damage, and redox
      markers during the season.
AB  - This study aimed to analyze changes in performance, muscle function, and stress
      related biochemical markers in professional soccer players (n = 14) at 4
      timepoints (3 for performance and 4 for stress-related biochemical markers)
      during the soccer season [Formula: see text] preseason (E1), midseason (E2), end
      of the season (E3) [Formula: see text] and after the end of the recovery period
      (E4). Performance in 5- and 30-m sprints, countermovement jump, and agility, and
      maximal isokinetic knee extension and knee flexion strength were measured (E1 to
      E3). We observed increased in-season levels of myoglobin (E2 > E1 and E4; p <
      0.05), a higher testosterone/cortisol ratio (T/C), and increased levels of
      creatine kinase (CK), C-reactive protein, superoxide dismutase (SOD), protein
      sulfhydryls (-SH), and malondialdehyde (E2 and E3 > E1 and E4; p < 0.05). Lower
      cortisol concentrations (E3 < E1 and E4; p < 0.05) and glutathione reductase
      activity (E3 < E2 and E4; p < 0.05) were observed at the end of the season. T/C,
      CK, SOD, -SH, and malondialdehyde decreased during the off-season, and cortisol
      and glutathione reductase increased (E3 < E4; p < 0.05). Agility increased in E2
      and E3 (p < 0.01). Significant correlations were found during the season between
      hormonal and muscle function parameters (r = 0.56-0.86; p < 0.05). In addition,
      in E2, significant associations were observed between match-accumulated time
      (MATE2; minutes played by each player during the competition period),
      performance, and hormonal and redox parameters (r = 0.456-0.615; p < 0.05). In
      conclusion, this study shows that soccer players face significant changes in
      biomarkers of physiologic strain (muscle damage and oxidative stress-related
      markers) during the season, but values return to normal during the off-season.
      Additionally, MAT influences physical, hormonal, and oxidative stress-related
      parameters in professional soccer players. 

PMID- 24669986
TI  - Effects of docosahexaenoic acid diet supplementation, training, and acute
      exercise on oxidative balance in neutrophils.
AB  - Diet supplementation with omega-3 fatty acids could influence the oxidative
      equilibrium, enhancing a pro-oxidant status. The aim was to determine the effects
      of diet supplementation with docosahexaenoic acid (DHA), training, and acute
      exercise on oxidative balance in neutrophils. Fifteen volunteer male soccer
      players were randomly assigned to a placebo or experimental group. The placebo
      group was supplemented with an almond-based beverage whereas the experimental
      group was supplemented with the same beverage enriched with DHA, in addition to
      their Mediterranean-type diet. Three blood samples were taken: in basal
      conditions at the beginning of the nutritional intervention and after 8 weeks of
      training season in basal and postexercise conditions. The training season
      significantly increased the antioxidant defenses of neutrophils, such as
      catalase, glutathione peroxidase and glutathione reductase enzyme activities; and
      decreased oxidative damage markers such as malondialdehyde, carbonyl and
      nitrotyrosine indexes. Oxidative damage markers decreased in neutrophils after
      acute exercise, which primed neutrophils to produce reactive oxygen and nitrogen
      species (RONS) after immune stimulation with zymosan or phorbol myristate acetate
      in trained footballers. DHA supplementation resulted in no significant effects on
      oxidative stress balance in neutrophils. In conclusion, DHA supplementation did
      not modify the adaptive response of the antioxidant system of neutrophils to
      training or the production of RONS induced by immune stimulation after acute
      exercise. 

PMID- 24669987
TI  - Mouth rinsing improves cycling endurance performance during Ramadan fasting in a
      hot humid environment.
AB  - This study examined the effect of mouth rinsing during endurance cycling in a hot
      humid environment (32  degrees C and 75% relative humidity) on athletes in the
      Ramadan fasted state. Nine trained adolescent male cyclists completed 3 trials
      that consisted of a carbohydrate mouth-rinse (CMR), a placebo mouth-rinse (PMR),
      and a no-rinse (NOR) trial during the last 2 weeks of Ramadan. Each trial
      consisted of a preloading cycle at 65% peak rate of oxygen consumption for 30 min
      followed by a 10-km time trial (TT10 km) under hot humid condition. During the
      CMR and PMR trials, each cyclist rinsed his mouth with 25 mL of the solution for
      5 s before expectorating the solution pre-exercise, after 5, 15, and 25 min of
      the preloading cycle, and 15 s prior to the start of TT10 km. Time to complete
      the TT10 km was significantly faster in the CMR and PMR trials compared with the
      NOR trial (12.9 +/- 1.7 and 12.6 +/- 1.7 vs. 16.8 +/- 1.6 min, respectively; p <
      0.017). Ratings of perceived exertion taken at the end of the TT10 km was lower
      in both CMR and PMR trials compared with the NOR trial, although the difference
      was significant only between CMR and NOR (p < 0.05). In conclusion, mouth rinsing
      with either carbohydrate or placebo solution provided ergogenic benefits compared
      with a no-rinse condition on TT10 km performance in acute Ramadan fasted subjects
      during endurance cycling in a heat stress environment. 

PMID- 24669988
TI  - A pilot program for physical exercise promotion in adults with type 1 diabetes:
      the PEP-1 program.
AB  - Physical inactivity is highly common in adults with type 1 diabetes (T1D) as
      specific barriers (i.e., hypoglycemia) may prevent them from being active. The
      objective of this study was to examine the efficacy of the Physical Exercise
      Promotion program in type 1 diabetes (PEP-1) program, a group program of physical
      activity (PA) promotion (intervention) compared with an information leaflet
      (control), to improve total energy expenditure (TEE) in adults with T1D after 12
      weeks. TEE was measured with a motion sensor over a 7-day period at inclusion,
      after the program (12 weeks) and 1-year after inclusion. The 12 weekly sessions
      of the program included a 30-min information session (glycemic control and PA)
      and 60 min of PA. A total of 48 adults, aged 18 to 65 years with a reported PA
      practice <150 min per week, were recruited (45.8% men; aged 44.6 +/- 13.3 years;
      8.0% +/- 1.1% glycated hemoglobin (A1c)) and randomized in this pilot trial.
      Ninety percent of participants completed the program and 88% completed the 1-year
      follow-up. No change was observed for TEE and A1c in both groups. After the 12
      week program, the mean peak oxygen uptake increased (14%; p = 0.003) in the
      intervention group; however, at the 1-year follow-up, it was no longer different
      from baseline. In the control group, no difference was observed for the peak
      oxygen uptake. These results suggest that the PEP-1 pilot program could increase
      cardiorespiratory fitness. However, this benefit is not sustained over a long
      term period. The PEP-1 program did not increase TEE in patients with T1D and
      other strategies remain necessary to counteract physical inactivity in this
      population. 

PMID- 24669990
TI  - The proportion of excessive fast-food consumption attributable to the
      neighbourhood food environment among youth living within 1 km of their school.
AB  - The study objective was to estimate the proportion of excessive fast-food
      consumption by youth that is attributable to living and attending school in a
      neighbourhood with a moderate or high density of fast-food restaurants. This was
      a cross-sectional study of 6099 Canadian youths (aged 11-15 years) from 255
      school neighbourhoods. All participants lived within 1 km of their school. The
      density of chain fast-food restaurants within a 1-km circular buffer surrounding
      each school was determined using geographic information systems. Excessive fast
      food consumption (>=2 times per week) was assessed by questionnaire. Multilevel
      logistic regression analysis was used to examine associations. The population
      attributable risk estimates of excessive fast-food consumption due to
      neighbourhood exposure to fast-food restaurants were determined based on the
      prevalence of exposure and the results from the logistic regression. Eight
      percent of participants were excessive fast-food consumers. After adjusting for
      sociodemographic factors (i.e., gender, race, and socioeconomic status), it was
      found that youths from neighbourhoods with a moderate (odds ratio (OR), 1.68; 95%
      confidence interval (CI), 1.11-2.54) or high (OR 1.70; 95% CI 1.12-2.56) density
      of chain fast-food restaurants were more likely to be excessive fast-food
      consumers than were youths from neighbourhoods with no chain fast-food
      restaurants. Approximately 31% of excessive consumption was attributable to
      living in neighbourhoods with a moderate or high density of fast-food
      restaurants. Thus, the fast-food retail environment within which youth live and
      go to school is an important contributor to their eating behaviours. 

PMID- 24669989
TI  - Differential effects of low-fat and high-fat diets on fed-state hepatic
      triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein
      expression in obese-prone Sprague-Dawley rats.
AB  - The purpose of this study was to compare the effects of short-term low-fat (LF)
      and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the
      content of proteins involved in TAG assembly and secretion, fatty acid oxidation
      (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese
      prone Sprague-Dawley rats, we directly measured fed-state hepatic TAG secretion,
      using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed
      meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF
      diet for 2 weeks, after which the rats were maintained on their respective diet
      for 1 week (washout) prior to the liver being excised to measure protein content,
      FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ~27%
      lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all
      other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion
      rate was ~39% lower (p < 0.05) in HF- (4.62 +/- 0.18 mmol.h(-1)) than in LF-
      (7.60 +/- 0.57 mmol.h(-1)) fed animals. Hepatic TAG content was ~2-fold higher (p
      < 0.05) in HF- (1.07 +/- 0.15 nmol.g(-1) tissue) than in LF- (0.50 +/- 0.16
      nmol.g(-1) tissue) fed animals. In addition, the fatty acid profile of liver TAG
      in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the
      fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was
      not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG
      secretion, hepatic fatty acid profiles, and DGAT-1 protein expression. 

PMID- 24669991
TI  - Neuroprotective efficacy of a combination of fish oil and ferulic acid against 3
      nitropropionic acid-induced oxidative stress and neurotoxicity in rats:
      behavioural and biochemical evidence.
AB  - The beneficial effects of fish oil (FO) supplements on the central nervous system
      have been adequately demonstrated. However, FO supplementation at higher doses
      for longer duration is likely to cause oxidative stress in vivo. To overcome
      this, attempts have been made to enrich FO with known
      antioxidants/phytochemicals. In the present study, we examined the hypothesis
      that a combination of FO with ferulic acid (FA), a naturally occurring phenolic
      compound, is likely to provide higher degree of neuroprotection. This was
      examined by employing 3-nitropropionic acid (NPA), a well-known neurotoxin used
      to mimic behavioural and neurochemical features of Huntington's disease. Growing
      male rats administered with NPA (25 mg/kg of body weight (bw) for 4 days) were
      provided with either FO (2 mL/kg bw), FA (50 mg/kg bw) or FO+FA for 2 weeks.
      Interestingly, FO+FA not only offered significant protection against NPA-induced
      behavioural impairments, but also markedly attenuated oxidative stress in brain
      regions (striatum/cerebellum) as evidenced by the reduction in reactive species,
      malondialdehyde, hydroperoxides and nitric oxide (NO) levels. Further, FO+FA
      combination restored the activities of various antioxidant enzymes and the levels
      of cytosolic calcium. In striatum, activity levels of acetylcholinesterase enzyme
      and dopamine levels were markedly restored among FO+FA rats. Interestingly, NPA
      induced mitochondrial dysfunctions were also attenuated among FO+FA rats.
      Collectively, our findings suggest the advantage of co-treatment of FO with known
      antioxidants to achieve a higher therapeutic benefit in the treatment of
      oxidative stress-mediated neurodegenerative conditions. 

PMID- 24669992
TI  - Healthy Eating Index is associated with certain markers of inflammation and
      insulin resistance but not with lipid profile in individuals at cardiometabolic
      risk.
AB  - Eating habits may influence inflammatory status and insulin resistance, both
      involved in the genesis of cardiometabolic diseases; an index of overall diet
      quality may be useful to identify risk for these diseases. We investigated
      whether the Healthy Eating Index (HEI-2005), adapted to Brazilian habits (B-HEI),
      was associated with markers of inflammation, insulin resistance and lipid profile
      in individuals at cardiometabolic risk. Two hundred and four prediabetic
      individuals (64.7% women) were enrolled in this cross-sectional study.
      Anthropometric measurements, 24-h dietary recalls used to calculate the B-HEI,
      and blood samples were collected. ANOVA was used for comparisons of clinical
      variables across the B-HEI tertiles and multiple linear regressions employed to
      test associations between clinical variables and B-HEI total score. Significant
      trends to decrease mean values of body mass index (BMI) (p = 0.03) and C-reactive
      protein concentrations (p = 0.02) across the tertiles of B-HEI, but not other
      biomarkers, were observed. Waist circumference, HOMA-IR and C-reactive protein
      were inversely associated with the B-HEI (p < 0.05), after adjusting for age,
      sex, BMI, and physical activity level. Also, a direct association of adiponectin
      concentrations with B-HEI was detected after adjustments (p = 0.001). Data from
      this study indicate that the B-HEI may be useful to identify the body adiposity
      induced pro-inflammatory status and insulin resistance in individuals at
      cardiometabolic risk. 

PMID- 24669993
TI  - Interrelationships between changes in anthropometric variables and computed
      tomography indices of abdominal fat distribution in response to a 1-year physical
      activity-healthy eating lifestyle modification program in abdominally obese men.
AB  - The objectives were to (i) measure the effects of a 1-year lifestyle modification
      program on body fat distribution/anthropometric variables; (ii) determine the
      interrelationships between changes in all these variables; and (iii) investigate
      whether there is a selective reduction in deep (DSAT) vs. superficial
      subcutaneous adipose tissue (SSAT) at the abdominal level following a 1-year
      lifestyle modification program. Anthropometric variables, body composition and
      abdominal and midthigh fat distribution were assessed at baseline and after 1
      year in 109 sedentary, dyslipidemic and abdominally obese men. Reductions in
      anthropometric variables, skinfold thicknesses (except the trunk/extremity ratio)
      and fat mass as well as an increase in fat-free mass were observed after 1 year
      (p < 0.0001). Decreases in abdominal adipose tissue volumes were also noted (
      23%, -26%, -18%, -19%, -17%, p < 0.0001 for total adipose tissue, visceral
      adipose tissue, subcutaneous adipose tissue, DSAT and SSAT, respectively).
      Adipose tissue areas at midthigh also decreased (-18%, -18%, -17%, p < 0.0001 for
      total, deep, and subcutaneous adipose tissue, respectively). A reduction (-9%, p
      < 0.0001) in low-attenuation muscle area and an increase (+1%, p < 0.05) in
      normal-attenuation muscle area were also observed. There was a positive
      relationship between changes in visceral adipose tissue and changes in DSAT (r =
      0.65, p < 0.0001) or SSAT (r = 0.63, p < 0.0001). Although absolute changes in
      DSAT were greater than changes in SSAT, relative changes in both depots were
      similar, independent of changes in visceral adipose tissue. The 1-year lifestyle
      modification program therefore improved the body fat distribution pattern and
      midthigh muscle quality in abdominally obese men. 

PMID- 24669996
TI  - IGF-1 colocalizes with muscle satellite cells following acute exercise in humans.
AB  - Insulin-like growth factor-1 (IGF-1) regulates stem cell proliferation and
      differentiation in vitro. The aim of this study was to quantify the change in
      satellite cell (SC) specific IGF-1 colocalization following exercise. We observed
      a significant increase (p < 0.05) in the percentage of SC with IGF-1
      colocalization from baseline to 72 h after a bout of resistance exercise. This
      strongly supports a role for IGF-1 in human SC function following exercise. 

PMID- 24669998
TI  - Communication and Food Messaging: The Consumer Disconnect "From scientific
      findings to useful consumer information".

PMID- 24669999
TI  - Reaction mechanism for the aqueous-phase mineral carbonation of heat-activated
      serpentine at low temperatures and pressures in flue gas conditions.
AB  - Mineral carbonation is known as one of the safest ways to sequester CO2.
      Nevertheless, the slow kinetics and low carbonation rates constitute a major
      barrier for any possible industrial application. To date, no studies have focused
      on reacting serpentinite with a relatively low partial pressure of CO2 (pCO2)
      close to flue gas conditions. In this work, finely ground and heat-treated
      serpentinite [Mg3Si2O5(OH)4] extracted from mining residues was reacted with a
      18.2 vol % CO2 gas stream at moderate global pressures to investigate the effect
      on CO2 solubility and Mg leaching. Serpentinite dissolution rates were also
      measured to define the rate-limiting step. Successive batches of gas were
      contacted with the same serpentinite to identify surface-limiting factors using
      scanning electron microscopy (SEM) analysis. Investigation of the serpentinite
      carbonation reaction mechanisms under conditions close to a direct flue gas
      treatment showed that increased dissolution rates could be achieved relative to
      prior work, with an average Mg dissolution rate of 3.55 * 10(-11) mol cm(-2) s(
      1). This study provides another perspective of the feasibility of applying a
      mineral carbonation process to reduce industrial greenhouse gas (GHG) emissions
      from large emission sources. 

PMID- 24670001
TI  - Highly stereoselective oxazaborolidinium ion catalyzed synthesis of (Z)-silyl
      enol ethers from alkyl aryl ketones and trimethylsilyldiazomethane.
AB  - Highly stereoselective (Z)-silyl enol ethers were prepared from alkyl aryl
      ketones and trimethylsilyldiazomethane (TMSD) using an oxazaborolidinium ion
      catalyst. In addition, ring-expanded silyl enol ethers were successfully
      constructed from cyclic ketones. Their synthetic utilities were shown by
      sequential Mukaiyama aldol and [2 + 2]-cycloaddition reactions. 

PMID- 24670000
TI  - Morbidity after conventional dissection of axillary lymph nodes in breast cancer
      patients.
AB  - BACKGROUND: Conventional axillary lymph node dissection (ALND) has recently
      become less radical. The treatment morbidity effects of reduced ALND
      aggressiveness are unknown. This article investigates the prevalence of the main
      complications of ALND: lymphedema, range-of-motion restriction, and arm
      paresthesia and pain. METHODS: This cross-sectional study included 200 women with
      invasive breast cancer who underwent breast-conserving surgery (82.5%, n = 165)
      or mastectomy (17.5%, n = 35) with ALND from 2007 to 2011. Arm perimetry was used
      to assess lymphedema, defined as a difference >2 cm in the upper arm
      circumference between the nonsurgical and surgical arms. Range-of-motion
      restriction was assessed by evaluating the degree of arm abduction. Paresthesia
      was measured in the inner and proximal arm regions. Arm pain was assessed by
      directly questioning the patients and defined as either present or absent.
      RESULTS: The average (+/-SD) time between ALND and morbidity evaluation was 35 +/
      18 months (range, 7-60 months). The average dissected lymph node number per
      patient was 14 +/- 4 (range, 6-30 lymph nodes). Only 3.5% (n = 7) of the patients
      presented with lymphedema. Single-incision approaches to breast tumor and ALND (P
      = 0.04) and the presence of a postoperative seroma (P = 0.02) were associated
      with lymphedema in univariate analysis. Paresthesia was the most frequent side
      effect observed (53% of patients, n = 106). This complication was associated with
      increased age (P < 0.0001) and a larger dissected lymph node number (P = 0.01) in
      univariate and multivariate analysis. Additionally, 24% (n = 48) of patients had
      noticeable limited arm abduction. Among the patients, 27.5% (n = 55) experienced
      sporadic arm pain corresponding to the surgically treated armpit. In multivariate
      analysis, the pain risk was 1.9-fold higher in patients who underwent ALND
      corresponding to their dominant arm (95% CI, 1.0-3.7, P = 0.04). CONCLUSION:
      Conventional ALND in breast cancer patients can result in unwanted complications.
      However, the current lymphedema prevalence is lower than that of the other
      analyzed side effects.

PMID- 24670002
TI  - Development and pilot testing of HIV screening program integration within
      public/primary health centers providing antenatal care services in Maharashtra,
      India.
AB  - BACKGROUND: The objectives of this paper are: (1) to study the feasibility and
      relative benefits of integrating the prevention of parent-to-child transmission
      (PPTCT) component of the National AIDS Control Program with the maternal and
      child health component of the National Rural Health Mission (NRHM) by offering
      HIV screening at the primary healthcare level; and (2) to estimate the
      incremental cost-effectiveness ratio to understand whether the costs are
      commensurate with the benefits. METHODS: The intervention included advocacy with
      political, administrative/health heads, and capacity building of health staff in
      Satara district, Maharashtra, India. The intervention also conducted biannual
      outreach activities at primary health centers (PHCs)/sub-centers (SCs); initiated
      facility-based integrated counseling and testing centers (FICTCs) at all round
      the-clock PHCs; made the existing FICTCs functional and trained PHC nurses in HIV
      screening. All "functional" FICTCs were equipped to screen for HIV and trained
      staff provided counseling and conducted HIV testing as per the national protocol.
      Data were collected pre- and post- integration on the number of pregnant women
      screened for HIV, the number of functional FICTCs and intervention costs. Trend
      analyses on various outcome measures were conducted. Further, the incremental
      cost-effectiveness ratio per pregnant woman screened was calculated. RESULTS: An
      additional 27% of HIV-infected women were detected during the intervention period
      as the annual HIV screening increased from pre- to post-intervention (55% to 79%,
      p < 0.001) among antenatal care (ANC) attendees under the NRHM. A greater
      increase in HIV screening was observed in PHCs/SCs. The proportions of functional
      FICTCs increased from 47% to 97% (p < 0.001). Additionally, 93% of HIV-infected
      pregnant women were linked to anti-retroviral therapy centers; 92% of mother-baby
      pairs received Nevirapine; and 89% of exposed babies were enrolled for early
      infant diagnosis. The incremental cost-effectiveness ratio was estimated at INR
      44 (less than 1 US$) per pregnant woman tested. CONCLUSIONS: Integrating HIV
      screening with the broader Rural Health Mission is a promising opportunity to
      scale up the PPTCT program. However, advocacy, sensitization, capacity building
      and the judicious utilization of available resources are key to widening the
      reach of the PPTCT program in India and elsewhere.

PMID- 24670003
TI  - Force field independent metal parameters using a nonbonded dummy model.
AB  - The cationic dummy atom approach provides a powerful nonbonded description for a
      range of alkaline-earth and transition-metal centers, capturing both structural
      and electrostatic effects. In this work we refine existing literature parameters
      for octahedrally coordinated Mn(2+), Zn(2+), Mg(2+), and Ca(2+), as well as
      providing new parameters for Ni(2+), Co(2+), and Fe(2+). In all the cases, we are
      able to reproduce both M(2+)-O distances and experimental solvation free
      energies, which has not been achieved to date for transition metals using any
      other model. The parameters have also been tested using two different water
      models and show consistent performance. Therefore, our parameters are easily
      transferable to any force field that describes nonbonded interactions using
      Coulomb and Lennard-Jones potentials. Finally, we demonstrate the stability of
      our parameters in both the human and Escherichia coli variants of the enzyme
      glyoxalase I as showcase systems, as both enzymes are active with a range of
      transition metals. The parameters presented in this work provide a valuable
      resource for the molecular simulation community, as they extend the range of
      metal ions that can be studied using classical approaches, while also providing a
      starting point for subsequent parametrization of new metal centers. 

PMID- 24670004
TI  - Primary care nurses' awareness of and willingness to perform children's oral
      health care.
AB  - BACKGROUND: The majority of young children receive no early dental examination
      while attending primary health care for routine check-ups. Our aim was to study
      primary care nurses' knowledge of oral health care (OHC) and their attitudes
      toward delivering OHC, as well as to assess their willingness to obtain OHC
      information. METHODS: We conducted a cross-sectional survey of all primary-care
      nurses working in the public health centres of Tehran city. An anonymous self
      administered questionnaire queried their knowledge in paediatric-, general and
      medicine-related areas of dentistry, providing knowledge scores for three
      domains. The nurses' attitudes toward OHC and their willingness to obtain OHC
      information underwent evaluation with statements utilizing a five-point Likert
      scale. Altogether 680 nurses took part in the survey. The Chi-square test, t
      test, one-way ANOVA and logistic regression model served for statistical
      analyses. RESULT: The mean score for the paediatric dentistry domain (3.6, SD:
      1.5) was lower than for the medical (4.4, SD: 2.3) and dental domains (5.8, SD:
      1.5). Obtaining higher scores in the paediatric (OR = 1.2) and dental (OR = 1.3)
      domains, and a greater willingness to receive OHC information (OR = 5.3), were
      associated with a positive attitude toward OHC. Nurses with a lower education (OR
      = 1.9) and better oral health behaviour (OR = 1.1) as well as those working in a
      non-affluent region (OR = 1.6) had a more positive attitude toward OHC.
      CONCLUSION: Primary care nurses' low level of knowledge in OHC and their positive
      attitude and willingness to obtain more information point to the need for
      appropriate OHC training and encouragement for the nurses to promote oral health
      and prevent dental diseases.

PMID- 24670005
TI  - Evidence-based recommendations for building better bras for women treated for
      breast cancer.
AB  - Participating in exercise is beneficial for women who have been treated for
      breast cancer. However, not being able to find a comfortable exercise bra can be
      a barrier to exercise participation. This study aimed to systematically
      investigate what breast support women treated for breast cancer want when they
      exercise in order to provide evidence-based recommendations to improve exercise
      bra designs for these women. Based on 432 responses from a national online
      survey, frequency and relationship data were analysed (binary logistic
      regression) to understand exercise bra issues pertinent to this population. These
      issues included being able to control for asymmetrical cup sizes, managing
      heightened skin sensitivity, managing fluid (size) fluctuations, managing a
      prosthesis and restoring body image by restoring shape. This study provides
      evidence-based recommendations to inform an exercise bra design that will meet
      the unique needs of women treated for breast cancer. Rigorous, evidence-based
      evaluations of exercise bras for women treated for breast cancer may contribute
      to their well-being and quality of life through enhanced designs.

PMID- 24670006
TI  - Curvature enhances binding and aggregation of huntingtin at lipid membranes.
AB  - Huntington disease (HD) is a genetic neurodegenerative disease caused by an
      expanded polyglutamine (polyQ) domain in the first exon of the huntingtin (Htt)
      protein, facilitating its aggregation. Htt interacts with a variety of
      membraneous structures within the cell, and the first 17 amino acids (Nt17) of
      Htt directly flanking the polyQ domain comprise an amphiphathic alpha-helix (AH)
      lipid-binding domain. AHs are also known to detect membrane curvature. To
      determine if Htt exon 1 preferentially binds curved membranes, in situ atomic
      force microscopy (AFM) studies were performed. Supported lipid bilayers are
      commonly used as model membranes for AFM studies of protein aggregation. However,
      these supported bilayers usually lack curvature. By forming a bilayer on top of
      silica nanobeads (50 +/- 10 nm) deposited on a silicon substrate, model supported
      lipid bilayers with flat and curved regions were developed for AFM studies. The
      presence of the bilayer over the beads was validated by continual imaging of the
      formation of the bilayer, height measurements, and spatially resolved mechanical
      measurements of the resulting bilayer using scanning probe acceleration
      microscopy. Interpretation of this data was facilitated by numerical simulations
      of the entire imaging process. The curved supported bilayers associated with the
      beads were found to be more compliant than flat supported bilayers, consistent
      with the altered packing density of lipids caused by the induced curvature. This
      model bilayer system was exposed to a synthetic truncated Htt exon 1 peptide
      (Nt17Q35P10KK), and this peptide preferentially accumulated on curved membranes,
      consistent with the ability of AHs to sense membrane curvature. 

PMID- 24670007
TI  - C2H2 treatment as a facile method to boost the catalysis of Pd nanoparticulate
      catalysts.
AB  - A facile method to boost the catalysis of Pd nanoparticulate catalysts by simple
      C2H2 treatment is developed. During the C2H2 treatment, Pd nanoparticles serve as
      active catalysts to polymerize C2H2 into trans-polyacetylene. The deposition of
      trans-polyacetylene layer on Pd nanoparticles makes their surface hydrophobic.
      Such a hydrophobic surface modification helps to accumulate more hydrophobic
      substrates during catalysis, making the modified Pd nanoparticulate catalysts
      more active than untreated catalysts in the catalytic reaction involving
      hydrophobic substrates. Moreover, the coating of polyacetylene on Pd creates
      encapsulated Pd nanocatalysts, stabilizing Pd nanoparticles against sintering or
      aggregation. Since the catalytic polymerization of polyacetylene on Pd is not
      facet dependent, the development is readily applied to enhance the catalysis of
      commercial Pd nanoparticulate catalysts by simple C2H2 treatment. 

PMID- 24670009
TI  - Discovery of 6-phenylpyrimido[4,5-b][1,4]oxazines as potent and selective acyl
      CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitors with in vivo efficacy in
      rodents.
AB  - The discovery and optimization of a series of acyl CoA:diacylglycerol
      acyltransferase 1 (DGAT1) inhibitors based on a pyrimido[4,5-b][1,4]oxazine
      scaffold is described. The SAR of a moderately potent HTS hit was investigated
      resulting in the discovery of phenylcyclohexylacetic acid 1, which displayed good
      DGAT1 inhibitory activity, selectivity, and PK properties. During preclinical
      toxicity studies a metabolite of 1 was observed that was responsible for
      elevating the levels of liver enzymes ALT and AST. Subsequently, analogues were
      synthesized to preclude the formation of the toxic metabolite. This effort
      resulted in the discovery of spiroindane 42, which displayed significantly
      improved DGAT1 inhibition compared to 1. Spiroindane 42 was well tolerated in
      rodents in vivo, demonstrated efficacy in an oral triglyceride uptake study in
      mice, and had an acceptable safety profile in preclinical toxicity studies. 

PMID- 24670008
TI  - Motor vehicle crash severity estimations by physicians and prehospital personnel.
AB  - OBJECTIVE: To determine whether emergency physicians (EPs) and prehospital
      emergency medical services (EMS) personnel differ in their assessment of motor
      vehicle crash (MVC) severity and the potential for serious injury when viewing
      crash scene photographs. METHODS: Attending and resident EPs, paramedics, and
      emergency medical technicians (EMTs) from a single emergency medicine system used
      a web-based survey platform to rate the severity of 100 crash photographs on a 10
      point Likert scale (Crash Score) and the potential for serious injury on a 0-100%
      scale (Injury Score). Serious injury was defined as skull fracture or
      intracranial bleeding, spine fracture or spinal cord injury, intrathoracic or
      intraabdominal injury, or long bone fracture. Crash and Injury Scores were
      stratified into EP and paramedic/EMT (EMS) groups and the mean score was
      calculated for each photo. Spearman rank correlation coefficients with 95%
      confidence intervals (95% CI) and Bland-Altman plots were constructed to assess
      agreement. Secondary analyses were performed after categorizing data into
      quartiles based on participants' estimations of MVC severity. RESULTS: A total of
      54 attending and 53 resident EPs, 156 paramedics, and 34 EMTs were invited to
      participate in the survey. Of these, 39 (72%) attending and 46 (87%) resident
      EPs, 107 (69%) paramedics, and 17 (50%) EMTs completed the survey. A total of 183
      (88%) surveys were completed in full. The overall Crash Score correlation
      coefficient between EPs and EMS was 0.98 (95% CI, 0.97-0.99). The Crash Score
      correlation coefficients for each quartile were 0.86 (0.57-0.97), 0.93 (0.85
      0.96), 0.58 (0.16-0.85), and 0.88 (0.66-0.97), respectively. The overall Injury
      Score correlation coefficient between EPs and EMS was 0.98 (0.88-0.97). The
      Injury Score correlation coefficients for each quartile were 0.94 (0.48-0.91),
      0.76 (0.50-0.92), 0.80 (0.69-1.00), and 0.94 (0.57-0.97), respectively.
      CONCLUSION: Although overall agreement between EPs and EMS personnel was
      excellent, differences in estimation of crash severity and potential for injury
      were identified among crashes estimated to be moderate in severity.

PMID- 24670010
TI  - Cone beam CT evaluation of the presence of anatomic accessory canals in the jaws.
AB  - OBJECTIVES: To assess the prevalence, location and anatomical course of accessory
      canals of the jaws using cone beam CT. METHODS: A retrospective analysis of 4200
      successive cone beam CT scans, for patients of both genders and ages ranging from
      7 to 88 years, was performed. They were exposed at the School of Dentistry,
      University of Michigan, Ann Arbor, MI. After applying the exclusion criteria (the
      presence of severe ridge resorption, pre-existing implants, a previously reported
      history of craniofacial malformations or syndromes, a previous history of trauma
      or surgery, inadequate image quality and subsequent scans from the same
      individuals), 4051 scans were ultimately included in this study. RESULTS: Of the
      4051 scans (2306 females and 1745 males) that qualified for inclusion in this
      study, accessory canals were identified in 1737 cases (42.9%; 1004 females and
      733 males). 532 scans were in the maxilla (13.1%; 296 females and 236 males) and
      1205 in the mandible (29.8%; 708 females and 497 males). CONCLUSIONS: A network
      of accessory canals bringing into communication the inner and outer cortical
      plates of the jaws was identified. In light of these findings, clinicians should
      carefully assess for the presence of accessory canals prior to any surgical
      intervention to decrease the risk for complications.

PMID- 24670011
TI  - mHealth and global mental health: still waiting for the mH2 wedding?
AB  - BACKGROUND: Two phenomena have become increasingly visible over the past decade:
      the significant global burden of disease arising from mental illness and the
      rapid acceleration of mobile phone usage in poorer countries. Mental ill-health
      accounts for a significant proportion of global disability-adjusted life years
      (DALYs) and years lived with disability (YLDs), especially in poorer countries
      where a number of factors combine to exacerbate issues of undertreatment. Yet
      poorer countries have also witnessed significant investments in, and dramatic
      expansions of, mobile coverage and usage over the past decade. DEBATE: The
      conjunction of high levels of mental illness and high levels of mobile phone
      usage in poorer countries highlights the potential for "mH(2)" interventions-
      i.e. mHealth (mobile technology-based) mental health interventions--to tackle
      global mental health challenges. However, global mental health movements and
      initiatives have yet to engage fully with this potential, partly because of
      scepticism towards technological solutions in general and partly because existing
      mH(2) projects in mental health have often taken place in a fragmented, narrowly
      focused, and small-scale manner. We argue for a deeper and more sustained
      engagement with mobile phone technology in the global mental health context, and
      outline the possible shape of an integrated mH(2) platform for the diagnosis,
      treatment, and monitoring of mental health. SUMMARY: Existing and developing
      mH(2) technologies represent an underutilised resource in global mental health.
      If development, evaluation, and implementation challenges are overcome, an
      integrated mH2 platform would make significant contributions to mental healthcare
      in multiple settings and contexts.

PMID- 24670012
TI  - Metatranscriptome analysis of fungal strains Penicillium camemberti and
      Geotrichum candidum reveal cheese matrix breakdown and potential development of
      sensory properties of ripened Camembert-type cheese.
AB  - BACKGROUND: Camembert-type cheese ripening is driven mainly by fungal microflora
      including Geotrichum candidum and Penicillium camemberti. These species are major
      contributors to the texture and flavour of typical bloomy rind cheeses.
      Biochemical studies showed that G. candidum reduces bitterness, enhances sulphur
      flavors through amino acid catabolism and has an impact on rind texture, firmness
      and thickness, while P. camemberti is responsible for the white and bloomy aspect
      of the rind, and produces enzymes involved in proteolysis and lipolysis
      activities. However, very little is known about the genetic determinants that
      code for these activities and their expression profile over time during the
      ripening process. RESULTS: The metatranscriptome of an industrial Canadian
      Camembert-type cheese was studied at seven different sampling days over 77 days
      of ripening. A database called CamemBank01 was generated, containing a total of
      1,060,019 sequence tags (reads) assembled in 7916 contigs. Sequence analysis
      revealed that 57% of the contigs could be affiliated to molds, 16% originated
      from yeasts, and 27% could not be identified. According to the functional
      annotation performed, the predominant processes during Camembert ripening include
      gene expression, energy-, carbohydrate-, organic acid-, lipid- and protein-
      metabolic processes, cell growth, and response to different stresses. Relative
      expression data showed that these functions occurred mostly in the first two
      weeks of the ripening period. CONCLUSIONS: These data provide further advances in
      our knowledge about the biological activities of the dominant ripening microflora
      of Camembert cheese and will help select biological markers to improve cheese
      quality assessment.

PMID- 24670013
TI  - Implementation and evaluation of the Helping Babies Breathe curriculum in three
      resource limited settings: does Helping Babies Breathe save lives? A study
      protocol.
AB  - BACKGROUND: Neonatal deaths account for over 40% of all under-5 year deaths;
      their reduction is increasingly critical for achieving Millennium Development
      Goal 4. An estimated 3 million newborns die annually during their first month of
      life; half of these deaths occur during delivery or within 24 hours. Every year,
      6 million babies require help to breathe immediately after birth. Resuscitation
      training to help babies breathe and prevent/manage birth asphyxia is not routine
      in low-middle income facility settings. Helping Babies Breathe (HBB), a
      simulation-training program for babies wherever they are born, was developed for
      use in low-middle income countries. We evaluated whether HBB training of facility
      birth attendants reduces perinatal mortality in the Eunice Kennedy Shriver
      National Institute of Child Health and Human Development's Global Network
      research sites. METHODS/DESIGN: We hypothesize that a two-year prospective pre
      post study to evaluate the impact of a facility-based training package, including
      HBB and essential newborn care, will reduce all perinatal mortality (fresh
      stillbirth or neonatal death prior to 7 days) among the Global Network's Maternal
      Neonatal Health Registry births >=1500 grams in the study clusters served by the
      facilities. We will also evaluate the effectiveness of the HBB training program
      changing on facility-based perinatal mortality and resuscitation practices.
      Seventy-one health facilities serving 52 geographically-defined study clusters in
      Belgaum and Nagpur, India, and Eldoret, Kenya, and 30,000 women will be included.
      Primary outcome data will be collected by staff not involved in the HBB
      intervention. Additional data on resuscitations, resuscitation debriefings, death
      audits, quality monitoring and improvement will be collected. HBB training will
      include training of MTs, facility level birth attendants, and quality monitoring
      and improvement activities. DISCUSSION: Our study will evaluate the effect of a
      HBB/ENC training and quality monitoring and improvement package on perinatal
      mortality using a large multicenter design and approach in 71 resource-limited
      health facilities, leveraging an existing birth registry to provide neonatal
      outcomes through day 7. The study will provide the evidence base, lessons
      learned, and best practices that will be essential to guiding future policy and
      investment in neonatal resuscitation. TRIAL REGISTRATION: Trial registration
      ClinicalTrials.gov Identifier: NCT01681017.

PMID- 24670015
TI  - Recognition.

PMID- 24670014
TI  - The influence of changes in trunk and pelvic posture during single leg standing
      on hip and thigh muscle activation in a pain free population.
AB  - BACKGROUND: Thigh muscle injuries commonly occur during single leg loading tasks
      and patterns of muscle activation are thought to contribute to these injuries.
      The influence trunk and pelvis posture has on hip and thigh muscle activation
      during single leg stance is unknown and was investigated in a pain free
      population to determine if changes in body posture result in consistent patterns
      of changes in muscle activation. METHODS: Hip and thigh muscle activation
      patterns were compared in 22 asymptomatic, male subjects (20-45 years old) in
      paired functionally relevant single leg standing test postures: Anterior vs.
      Posterior Trunk Sway; Anterior vs. Posterior Pelvic Rotation; Left vs. Right
      Trunk Shift; and Pelvic Drop vs. Raise. Surface EMG was collected from eight hip
      and thigh muscles calculating Root Mean Square. EMG was normalized to an "upright
      standing" reference posture. Repeated measures ANOVA was performed along with
      associated F tests to determine if there were significant differences in muscle
      activation between paired test postures. RESULTS: In right leg stance, Anterior
      Trunk Sway (compared to Posterior Sway) increased activity in posterior sagittal
      plane muscles, with a concurrent deactivation of anterior sagittal plane muscles
      (p: 0.016 - <0.001). Lateral hip abductor muscles increased activation during
      Left Trunk Shift (compared to Right) (p :<= 0.001). Lateral Pelvic Drop (compared
      to Raise) decreased activity in hip abductors and increased hamstring, adductor
      longus and vastus lateralis activity (p: 0.037 - <0.001). CONCLUSION: Changes in
      both trunk and pelvic posture during single leg stance generally resulted in
      large, predictable changes in hip and thigh muscle activation in asymptomatic
      young males. Changes in trunk position in the sagittal plane and pelvis position
      in the frontal plane had the greatest effect on muscle activation. Investigation
      of these activation patterns in clinical populations such as hip and thigh muscle
      injuries may provide important insights into injury mechanisms and inform
      rehabilitation strategies.

PMID- 24670017
TI  - Complications associated with postoperative adjuvant radiation therapy for
      advanced rectal cancer.
AB  - Preoperative management of advanced rectal cancer often includes
      chemoradiotherapy, but little is known about the late complications of
      radiotherapy. However, these are usually serious, making determination of the
      characteristics of late complications after radiation therapy critical.
      Accordingly, we investigated the complications occurring after adjuvant pelvic
      radiation therapy in patients with advanced rectal cancer. We enrolled 34
      consecutive patients with TNM stage III rectal cancer who had undergone curative
      surgery with adjuvant pelvic radiation therapy. Data on the type of
      complication/organ involved, the number of complications, the phase of onset, and
      the treatments used were reviewed. Patients who experienced gut complications or
      edema were less likely to have their complications resolved than those with
      complications due to infection. Similarly, patients with multiple complications
      and late-onset complications were also less likely to have their complications
      resolved than those with single complications and those with early-onset
      complications, respectively. Adjuvant radiation therapy in patients with resected
      advanced rectal cancer was associated with various complications, characterized
      by late onset and impaired resolution. Therefore, patients indicated for
      radiation therapy should be selected with great caution.

PMID- 24670018
TI  - The role of 3-D endorectal ultrasound in rectal cancer: our experience.
AB  - In the last 20 years, endorectal ultrasound (ERUS) has been one of the main
      diagnostic methods for locoregional staging of rectal cancer. ERUS is accurate
      modality for evaluating local invasion of rectal carcinoma into the rectal wall
      layers (T category). Adding the three-dimensional modality (3-D) increases the
      capabilities of this diagnostic tool in rectal cancer patients. We review the
      literature and report our experience in preoperative 3-D ERUS in rectal cancer
      staging. In the group of 71 patients, the staging of preoperative 3-D endorectal
      ultrasonography was compared with the postoperative morphologic examination.
      Three-dimensional ERUS preoperative staging was confirmed with morphologic
      evaluation in 66 out of 71 cases (92.9%). The detection sensitivities of rectal
      cancer with 3-D ERUS were as follows: T1, 92.8%; T2, 93.1%; T3, 91.6%; and T4,
      100.0%; with specificity values of T1, 98.2%; T2, 95.4%; T3, 97.8%; and T4,
      98.5%. Three-dimensional ERUS correctly categorized patients with T1, 97.1%; T2,
      94.3%; T3, 95.7%; and T4, 98.5%. The percentage of total overstaged cases was
      2.75% and that of understaged cases was 6.87%. The metastatic status of the lymph
      nodes was determined with a sensitivity of 79.1% (19 of 24), specificity of 91.4%
      (43 of 47), and diagnostic accuracy of 87.3% (62 of 71). In our experience, 3-D
      ERUS has the potential to become the diagnostic modality of choice for the
      preoperative staging of rectal cancer.

PMID- 24670019
TI  - Incidence and mortality of anastomotic dehiscence requiring reoperation after
      rectal carcinoma resection.
AB  - Anastomotic dehiscence (AD) requiring reoperation is the most severe complication
      following anterior rectal resection. We performed a systematic review on studies
      that describe AD requiring reoperation and its subsequent mortality after
      anterior resection for rectal carcinoma. A systematic search was performed on
      published literature. Data on the definition and rate of AD, the number of ADs
      requiring reoperation, the mortality caused by AD, and the overall postoperative
      mortality were pooled and analyzed. A total of 39 studies with 24,232 patients
      were analyzed. The studies varied in incidence and definition of AD. Systematic
      review of the data showed that the overall rate of AD was 8.6%, and the rate of
      AD requiring reoperation was 5.4%. The postoperative mortality caused by AD was
      0.4%, and the overall postoperative mortality was 1.3%. We found considerable
      risk and mortality for AD requiring reoperation, which largely contributed to the
      overall postoperative mortality.

PMID- 24670020
TI  - Surgical management in enterovesical fistula in Crohn disease at a single medical
      center.
AB  - Crohn disease is a chronic, transmural, inflammatory disease of the
      gastrointestinal tract with unknown etiology. It can affect any part of the
      gastrointestinal tract and may cause fistula, stricture, or abscess formation
      with disease progression. The preoperative diagnosis and definite management of
      this rare complication are challenges for physicians, urologists, and surgeons.

PMID- 24670021
TI  - Gossypiboma presenting as coloduodenal fistula--report of a rare case with review
      of literature.
AB  - The term gossypiboma is used to describe a mass of cotton matrix left behind in a
      body cavity intraoperatively. The most common site reported is the abdominal
      cavity. It can present with abscess, intestinal obstruction, malabsorption,
      gastrointestinal hemorrhage, and fistulas. A 37-year-old woman presented with
      pain in the right hypochondrium for 2 months following open cholecystectomy. As
      she did not improve with proton pump inhibitors, an esophagogastroduodenoscopy
      (EGD) was done, which showed a possible gauze piece stained with bile in the
      first part of the duodenum. Contrast-enhanced computed tomography (CECT) of the
      abdomen revealed an abnormal fistulous communication of the first part of
      duodenum with proximal transverse colon, with a hypodense, mottled lesion within
      the lumen of the proximal transverse colon plugging the fistula, suggestive of a
      gossypiboma. Excision of the coloduodenal fistula, primary duodenal repair, and
      feeding jejunostomy was done. The patient recovered well and is now tolerating
      normal diet. Coloduodenal fistula is usually caused by Crohn's disease,
      malignancy, right-sided diverticulitis, and gall stone disease. Isolated
      coloduodenal fistula due to gossypiboma has not been reported in the literature
      so far to the best of our knowledge. We report this case of coloduodenal fistula
      secondary to gossypiboma for its rarity and diagnostic challenge.

PMID- 24670022
TI  - A case of very well-differentiated adenocarcinoma with carcinoid tumor in the
      ascending colon.
AB  - Malignant tumors with mixed glandular and neuroendocrine characteristics with at
      least 30% of each component are classified as mixed adenoneuroendocrine carcinoma
      (MANEC) by the World Health Organization 2010 classification. We report here a
      case of very well-differentiated adenocarcinoma accompanied by carcinoid tumor,
      categorized as MANEC. A 41-year-old Japanese man was clinically diagnosed with
      ascending colon cancer and underwent right hemicolectomy. Using an
      immunohistologic technique, the pathologic diagnosis was very well-differentiated
      adenocarcinoma accompanied by carcinoid tumor and marked eosinophil infiltration,
      which was categorized as MANEC. By immunohistochemical analysis, tumor cells of
      the carcinoid component exhibited very low proliferation activity. Our case was
      thought to be MANEC without high malignant potential. MANEC as per the World
      Health Organization 2010 classification seems to include tumors with diverse
      grades of malignancy, and it might need to have subclassifications according to
      the malignancy potential of the tumor cells.

PMID- 24670023
TI  - A novel modified laryngeal mask airway allowing full separation of the digestive
      and respiratory tracts, along with double-catheter ventilation, diagnosis, and
      treatment.
AB  - The aim of this study was to design a novel, modified, multifunctional, and safe
      laryngeal mask airway (LMA). We designed an LMA with an internal catheter
      extending beyond the tip of the cuff. The protruding end of the internal catheter
      was provided with a catheter cuff, the space between the internal and external
      catheters was ventilatory, and the inlet ends of the 2 catheters were provided
      with standard connectors. We found that this design prevented reflux or
      aspiration of gastric content into the airway, prevented LMA dislocation, allowed
      ventilation through both the internal and external catheters, and allowed
      endoscopic examination and treatment of the gastrointestinal and respiratory
      tracts through both the internal and external catheters. This design overcomes
      the drawbacks and extends the functions of previous LMAs, offering a new approach
      to the development of LMAs.

PMID- 24670024
TI  - Cephalosporin induced disulfiram-like reaction: a retrospective review of 78
      cases.
AB  - Concomitant ingestion of alcohol and cephalosporin may cause a disulfiram-like
      reaction; however its fatal outcomes are not commonly known. We retrospectively
      reviewed 78 patients who had cephalosporin induced disulfiram-like reaction
      (CIDLR). The patients who had a negative skin test to cephalosporin prior to
      intravenous antibiotics were included, and those who were allergic to either
      alcohol or antibiotics were excluded. The average age of 78 patients was 37.8+/
      12.2 (21-60) years. Of the 78 patients, 93.58% of the patients were males, 70.51%
      of the patients consumed alcohol after use of antibiotics, and 29.49% patients
      consumed alcohol initially, followed by intravenous antibiotics; however, no
      significant difference of morbidity was observed in these two groups. All
      patients were administered antibiotics intravenously. Five of 78 patients (6.41%)
      developed severe CIDLR too urgently to be rescued successfully. In conclusion, it
      is important for clinicians to educate patients that no alcohol should be used if
      one is taking cephalosporin. Also, clinicians should keep in mind that
      cephalosporin should not be prescribed for any alcoholics.

PMID- 24670025
TI  - Effect of topical tetracycline on seroma formation in the Lichtenstein technique:
      a prospective randomized study.
AB  - We sought to investigate whether application of topical tetracycline has a
      limiting effect on seroma formation in patients undergoing hernia repair using a
      polypropylene mesh. This study was conducted in 96 patients undergoing an
      elective groin hernia repair. Patients were randomized and divided into 2 groups.
      After the graft was placed, and before external oblique muscle aponeurosis was
      closed, 5 mL tetracycline was administered on the graft in the tetracycline group
      (tetra group, n = 50), and 5 mL isotonic saline was administered in the control
      group (n = 46) without putting in a drain. Seroma checks via surface
      ultrasonography were done. Seroma amounts measured on the first day were
      significantly higher in the tetra group (P = 0.04). There were no significant
      differences regarding seroma measurements on the seventh day or in the first and
      second months. Topical tetracycline application has no limiting effect on seroma
      formation after a groin hernia operation.

PMID- 24670027
TI  - Analysis of potential oral cleft risk factors in the Kosovo population.
AB  - The aim of this study was to analyze the association of potential risk factors
      such as positive family cleft history, smoking, use of drugs during pregnancy,
      and parental age with oral clefts in offspring within the Kosovo population. We
      conducted a population-based case-control study of live births in Kosovo from
      1996 to 2005. Using a logistic regression model, 244 oral cleft cases were
      compared with 488 controls. We have excluded all syndromic clefts. Heredity
      increases the risk of clefts in newborns [odds ratio (OR) = 8.25, 95% confidence
      interval (CI) 3.12-23.52]. Clefts were also associated with smoking (OR = 1.87,
      95% CI 0.75-4.08), use of drugs during pregnancy (OR = 2.25, 95% CI 0.82-5.12),
      increasing maternal age (OR = 1.83, 95% CI 1.42-2.49), and increasing paternal
      age (OR = 1.3, 95% CI 1.2- 1.4). We found heredity to be the most important
      factor for cleft occurrence in Kosovar newborns. Another significant potential
      risk factor for occurrence of clefts is the parental age. We found the use of
      drugs and smoking during pregnancy to be less significant.

PMID- 24670026
TI  - Outcome of hepatectomy for hepatocellular carcinoma in elderly patients with
      portal hypertension.
AB  - The outcome of liver resection (LR) for elderly hepatocellular carcinoma (HCC)
      patients with portal hypertension (PHT) who may be excluded as liver
      transplantation candidates has not been fully evaluated. One hundred ninety-five
      patients who underwent initial curative LR for HCC with PHT were divided into 2
      groups: age <70 years (n = 131) and age >=70 years (n = 64). Clinicopathologic
      data and postoperative complications were compared. Preoperative characteristics
      and postoperative complications were similar in both groups. However, in-hospital
      mortality was significantly more frequent in elderly than in younger patients
      (11% versus 1%, P = 0.002). No significant intergroup differences were observed
      in the 5-year disease-free survival rate or recurrence rate (19.7% versus 17.2%;
      P = 0.338, 63% versus 56%; P = 0.339). Although LR for elderly HCC patients with
      PHT can be performed with curative intent and gives results comparable with those
      in younger patients, it is associated with higher in-hospital mortality.

PMID- 24670028
TI  - Prognostic factors for gastrectomy in elderly patients.
AB  - The decision to undergo surgery for gastric cancer patients aged >=85 years
      should be made carefully. We retrospectively reviewed the prognostic factors of
      gastrectomy for 64 patients aged >=85 years who had undergone curative
      gastrectomy for gastric cancer. The effects of various clinical characteristics
      and surgical interventions on survival were retrospectively analyzed. Univariate
      analysis revealed that sex (male/female; P = 0.001), the extent of gastric
      resection (total/distal; P = 0.028), the extent of lymph node dissection (D2/<D2;
      P = 0.019), and blood loss (P = 0.005) were significant prognostic factors for
      overall survival. Multivariate analysis demonstrated that sex was the only
      independent prognostic factor. For pneumonia-specific survival, sex was also the
      only prognostic factor by multivariate analysis.Prognoses of males aged >=85
      years after gastrectomy were significantly worse than those of females, as they
      were more likely to die of pneumonia.

PMID- 24670029
TI  - Significance of the lower esophageal sphincter preservation in preventing
      alkaline reflux esophagitis in patients after total gastrectomy reconstructed by
      Roux-en-Y for gastric cancer.
AB  - To clarify the significance of the lower esophageal sphincter (LES) for
      prevention of alkaline reflux esophagitis (ARE) after total gastrectomy
      reconstructed by Roux-en-Y (TGRY) for gastric cancer, we investigated LES
      function and lower esophageal pH in TGRY patients with or without LES
      preservation. A total of 51 patients 5 years after TGRY were divided into groups
      A (26 patients without preserved LES) and B (25 patients with preserved LES) and
      compared with 22 control participants (group C). Manometric study and ambulatory
      24-hour esophageal pH monitoring were performed on all patients. Symptomatic and
      endoscopic AREs in group A were significantly higher than those in group B (P <
      0.05). The length of LES and maximum LES pressure in group A were significantly
      shorter and lower, respectively, than in groups B and C (P < 0.01). The length of
      LES and maximum LES pressure in patients with symptomatic ARE were significantly
      shorter and lower, respectively, than in patients without symptomatic ARE (P <
      0.01). Percentages of time with pH >7 and pH >8 within 24 hours in group A were
      significantly higher than those in groups B and C (P < 0.01). Preservation of the
      LES may be necessary to prevent ARE after TGRY.

PMID- 24670030
TI  - A comparison of outcomes and complications of totally implantable access port
      through the internal jugular vein versus the subclavian vein.
AB  - Totally implantable access ports (TIAPs) are generally used in oncology. Few
      studies have addressed complications associated with the insertion site. A total
      of 233 consecutive oncology patients were enrolled to receive TIAP inserts via
      internal jugular vein (IJV) or subclavian vein (SV). Data on clinicopathologic
      parameters and early/late complications were retrospectively collected. No
      differences were found early and late complication rates. Catheter injury was
      observed more frequently in the IJV group (2.9%) than in the SV group (1.0%)
      without statistical significance. Multivariate logistic regression analysis
      showed that age, switch to palliative use of TIAP, and the distribution of
      diseases (low risk in patients with colorectal cancer) were independent risk
      factors for determining complications. In conclusion, TIAP insertion site showed
      no impact on the early and late complication rates. Catheter injury appears to
      occur at the same frequency with both approaches. Therefore, medical doctors may
      choose their preferred puncture site when performing TIAP insertion.

PMID- 24670031
TI  - Grey relational analysis of benefit of surgical management for abdominal aortic
      aneurysm.
AB  - Grey relational analysis was used to compare the long-term outcomes of
      endovascular repair (EVAR) versus open repair for patients with abdominal aortic
      aneurysm (AAA). Patients with AAA undergoing open repair (n = 133) or EVAR (n =
      88) from July 1995 to January 2009 were studied retrospectively. Compared with
      EVAR, longer periods of postoperative intubation and hospital stay (P < 0.001)
      were required for open repair. The operation time was significantly longer in
      open surgery than in EVAR (P < 0.001). Patients in the open repair group required
      larger volumes of intraoperative blood transfusion than those in EVAR (P <
      0.001), and they had more of a trend of cardiac failure after surgery than those
      in the EVAR group. The operative mortality was similar in both groups. On follow
      up, the all-cause mortality and the rates of ischemic legs within 5 years had no
      significant differences between the 2 procedures (P > 0.05). The grey relational
      grades in EVAR and open repair were 0.673 and 0.936, respectively. Compared with
      open repair, patients with AAAs undergoing EVAR had fewer complications in the
      short term and had a similar all-cause mortality in the long term.

PMID- 24670032
TI  - Proteasome inhibition induces both antioxidant and hb f responses in sickle cell
      disease via the nrf2 pathway.
AB  - Oxidant stress is implicated in the manifestations of sickle cell disease
      including hemolysis and vascular occlusion. Strategies to induce antioxidant
      response as well as Hb F (alpha2gamma2) have the potential to ameliorate the
      severity of sickle cell disease. Nuclear factor (erythroid-derived 2)-like 2
      (NFE2L2 or Nrf2) is a transcription factor that regulates antioxidant enzymes as
      well as gamma-globin transcription. The Nrf2 in the cytoplasm is bound to its
      adapter protein Keap-1 that targets Nrf2 for proteasomal degradation, thereby
      preventing its nuclear translocation. We examined whether inhibiting the 26S
      proteasome using the clinically applicable proteasome inhibitors bortezomib and
      MLN 9708 would promote nuclear translocation of Nrf2, and thereby induce an
      antioxidant response and as well as Hb F in sickle cell disease. Proteasome
      inhibitors induced reactive oxygen species (ROS) and thereby increased Nrf2
      dependent antioxidant enzyme transcripts, elevated cellular glutathione (GSH)
      levels and gamma-globin transcripts as well as Hb F levels in the K562 cell line
      and also in erythroid burst forming units (BFU-E) generated from peripheral blood
      mononuclear cells of sickle cell disease patients. These responses were abolished
      by siRNA-mediated knockdown of Nrf2. Proteasome inhibitors, especially newer oral
      agents such as MLN9708 have the potential to be readily translated to clinical
      trials in sickle cell disease with the dual end points of antioxidant response
      and Hb F induction.

PMID- 24670034
TI  - Co-precipitation of radium with barium and strontium sulfate and its impact on
      the fate of radium during treatment of produced water from unconventional gas
      extraction.
AB  - Radium occurs in flowback and produced waters from hydraulic fracturing for
      unconventional gas extraction along with high concentrations of barium and
      strontium and elevated salinity. Radium is often removed from this wastewater by
      co-precipitation with barium or other alkaline earth metals. The distribution
      equation for Ra in the precipitate is derived from the equilibrium of the lattice
      replacement reaction (inclusion) between the Ra(2+) ion and the carrier ions
      (e.g., Ba(2+) and Sr(2+)) in aqueous and solid phases and is often applied to
      describe the fate of radium in these systems. Although the theoretical
      distribution coefficient for Ra-SrSO4 (Kd = 237) is much larger than that for Ra
      BaSO4 (Kd = 1.54), previous studies have focused on Ra-BaSO4 equilibrium. This
      study evaluates the equilibria and kinetics of co-precipitation reactions in Ra
      Ba-SO4 and Ra-Sr-SO4 binary systems and the Ra-Ba-Sr-SO4 ternary system under
      varying ionic strength (IS) conditions that are representative of brines
      generated during unconventional gas extraction. Results show that radium removal
      generally follows the theoretical distribution law in binary systems and is
      enhanced in the Ra-Ba-SO4 system and restrained in the Ra-Sr-SO4 system by high
      IS. However, the experimental distribution coefficient (Kd') varies widely and
      cannot be accurately described by the distribution equation, which depends on IS,
      kinetics of carrier precipitation and does not account for radium removal by
      adsorption. Radium removal in the ternary system is controlled by the co
      precipitation of Ra-Ba-SO4, which is attributed to the rapid BaSO4 nucleation
      rate and closer ionic radii of Ra(2+) with Ba(2+) than with Sr(2+). Carrier
      (i.e., barite) recycling during water treatment was shown to be effective in
      enhancing radium removal even after co-precipitation was completed. Calculations
      based on experimental results show that Ra levels in the precipitate generated in
      centralized waste treatment facilities far exceed regulatory limits for disposal
      in municipal sanitary landfills and require careful monitoring of allowed source
      term loading (ASTL) for technically enhanced naturally occurring materials
      (TENORM) in these landfills. Several alternatives for sustainable management of
      TENORM are discussed. 

PMID- 24670033
TI  - Protein-based therapies for acute lung injury: targeting neutrophil extracellular
      traps.
AB  - INTRODUCTION: Acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) are the acute onset of noncardiac respiratory insufficiency associated
      with bilateral lung infiltrations. During the past decade, mechanical ventilation
      strategies using low tidal volumes have reduced the mortality of ALI/ARDS to ~ 20
      - 40%. However, ALI/ARDS continues to be a major factor in global burden of
      diseases, with no pharmacological agents currently available. AREAS COVERED: In
      this review, we discuss several inflammatory proteins involved in the molecular
      pathogenesis of ALI/ARDS. The complement cleavage product, C5a, is a peptide
      acting as a potent anaphylatoxin. C5a may trigger the formation of neutrophil
      extracellular traps (NETs) and release of histone proteins to the extracellular
      compartment during ALI/ARDS. NETs may activate platelets to release TGF-beta,
      which is involved in tissue remodeling during the later phases of ALI/ARDS.
      Interception of C5a signaling or blockade of extracellular histones has recently
      shown promising beneficial effects in small animal models of ALI/ARDS. EXPERT
      OPINION: Novel protein-based strategies for the treatment of ALI/ARDS may inspire
      the hopes of scientists, clinicians, and patients. Although neutralization of
      extracellular histones/NETs, C5a, and TGF-beta is effective in experimental
      models of ALI/ARDS, controlled clinical trials will be necessary for further
      evaluation in future.

PMID- 24670035
TI  - Temporal patterns of cortical proliferation of glial cell populations after
      traumatic brain injury in mice.
AB  - TBI (traumatic brain injury) triggers an inflammatory cascade, gliosis and cell
      proliferation following cell death in the pericontusional area and surrounding
      the site of injury. In order to better understand the proliferative response
      following CCI (controlled cortical impact) injury, we systematically analyzed the
      phenotype of dividing cells at several time points post-lesion. C57BL/6 mice were
      subjected to mild to moderate CCI over the left sensory motor cortex. At
      different time points following injury, mice were injected with BrdU
      (bromodeoxyuridine) four times at 3-h intervals and then killed. The greatest
      number of proliferating cells in the pericontusional region was detected at 3 dpi
      (days post-injury). At 1 dpi, NG2+ cells were the most proliferative population,
      and at 3 and 7 dpi the Iba-1+ microglial cells were proliferating more. A
      smaller, but significant number of GFAP+ (glial fibrillary acidic protein)
      astrocytes proliferated at all three time points. Interestingly, at 3 dpi we
      found a small number of proliferating neuroblasts [DCX+ (doublecortin)] in the
      injured cortex. To determine the cell fate of proliferative cells, mice were
      injected four times with BrdU at 3 dpi and killed at 28 dpi. Approximately 70% of
      proliferative cells observed at 28 dpi were GFAP+ astrocytes. In conclusion, our
      data suggest that the specific glial cell types respond differentially to injury,
      suggesting that each cell type responds to a specific pattern of growth factor
      stimulation at each time point after injury.

PMID- 24670038
TI  - Enantioselective total synthesis of (-)-walsucochin B.
AB  - The first enantioselective total synthesis of the structurally unique
      nortriterpenoid (-)-walsucochin B has been accomplished through the cationic
      polyolefin cyclization initiated by chiral epoxide. The core framework and the
      stereocenters in the natural product were all constructed in this step. A site
      selective, late-stage free-radical halogenation and Seyferth-Gilbert homologation
      was adopted to install the acetylene moiety to synthesize the phenylacetylene.
      The absolute configuration of walsucochin B was confirmed through
      enantioselective total synthesis. 

PMID- 24670037
TI  - Utilization of information and communication technology (ICT) among sexually
      transmitted disease clinics attendees with coexisting drinking problems.
AB  - BACKGROUND: Alcohol misuse remains a major risk factor for contracting sexually
      transmitted diseases (STDs) not typically addressed in STD clinic settings.
      Information and communication technology (ICT) can offer new avenues to deliver
      evidence-based screening and treatment for problematic drinking, however, few
      data exists regarding the utilization of ICT among STD clinic attendees with
      coexisting drinking problems. The objectives of this study are to identify STD
      clinics attendees with hazardous drinking, to examine socio-demographic factors
      associated with ICT use, and to explore individuals' interests in engaging in ICT
      based health interventions. METHODS: Cross-sectional questionnaires examining
      alcohol consumption and ICT use were administered to 396 persons attending two
      non-urban STD clinics. Descriptive statistics for ICT use were calculated for
      both hazardous drinkers and the entire sample. Multivariable logistic regression
      models among hazardous drinkers identified factors significantly associated with
      use of each kind of ICT. RESULTS: The mean age of the 396 participants was 25
      years, 66% were females and 60% were African-Americans. One third of the sample
      met the criteria of hazardous drinking. ICT use in hazardous drinkers included
      94% reporting having internet access at least monthly, 82% reporting having an
      email account, 85% reporting currently owning a cell phone, and 91% reporting use
      of any cell phone application. More than two thirds (73%) of hazardous drinkers
      were willing to play health-related video games during clinic waiting time,
      slightly higher than the entire sample (69%). Multivariable analyses indicated
      that younger age were significantly related to monthly internet use, and
      multifunction cell phone use, while being males and younger age were
      significantly associated with monthly video game playing. CONCLUSIONS: Our study
      demonstrates commonality of ICT use among STD clinic attendees with hazardous
      drinking, indicating the viability of using ICT to assist screening and
      behavioural intervention for alcohol misuse in STD clinic settings. Future
      research is needed to demonstrate the effectiveness of ICT-based health
      behavioural interventions in the STD clinic settings or other venues that serve
      populations at high risk for substance abuse, HIV or other STDs.

PMID- 24670039
TI  - Observation of transient alignment-inversion walls in nematics of phenyl
      benzoates in the presence of a magnetic field.
AB  - Formation of new transient walls by a constant magnetic field at the Freedericsz
      critical value has been observed. They are oriented along the initial alignment
      of the nematic phase of phenyl benzoates and appeared only in relatively thick
      samples with a thickness between 50 and 100 MUm of the cells. The excellent
      planarity of the liquid crystal orientation is considered to be the most
      important condition for their presence These magnetic walls are transient as they
      disappear either after a few seconds for 100 MUm thick nematic cells or after
      parts of a second for thinner (50 MUm) nematic cells. Nonregular stable magnetic
      walls, incorporating disclinations with core, appear immediately after the
      relaxation of the transient walls, when the planarity of the nematic orientation
      is not perfect. In thinner nematic cells of 20 MUm or less, a Freedericksz
      transition has only been observed. The formation of transient magnetic walls can
      be described by a model taking into account alignment-inversion, twisted along Y
      regions. The transient walls accompanied by a system of Becke lines relax by
      going through three-dimensional twist-splay-bend deformations. 

PMID- 24670040
TI  - General Practitioners' experiences of bereavement care and their educational
      support needs: a qualitative study.
AB  - BACKGROUND: General Practitioners (GPs) are well-positioned to provide grief
      support to patients. Most GPs view the provision of bereavement care as an
      important aspect of their role and the GP is the health professional that many
      people turn to when they need support. We aimed to explore GPs' understandings of
      bereavement care and their education and professional development needs in
      relation to bereavement care. METHODS: An in-depth qualitative design was adopted
      using a social constructionist approach as our aims were exploratory and applied.
      Nineteen GPs (12 women and 7 men) living in Western Australia were interviewed;
      14 were based in metropolitan Perth and 5 in rural areas. GPs were invited, via a
      letter, to participate in a semi-structured interview. The interviews occurred
      within each GP's workplace or, for the rural GPs, via telephone, and all
      interviews were digitally audio-recorded and transcribed. RESULTS: Analysis was
      based upon constant comparison and began as soon as possible after each
      interview. The data revealed four tensions or opposing views concerning
      bereavement and bereavement care. These were (1) whether grief is a standardised
      versus an individual process, (2) the role of the GP in intervening versus
      promoting resilience, (3) the GP as a broker of services versus a service
      provider, and (4) the need for formal education and professional development
      versus 'on-the-job' experiential learning. CONCLUSIONS: GPs have a critical role
      in exploring distress, including grief. However, changes need to be made to
      ensure GPs have up-to-date knowledge of contemporary theories and approaches. GPs
      urgently need education both at the undergraduate and postgraduate degree levels,
      and in continuing professional development. Otherwise GPs will rely on out-dated
      theories and constructions of grief, which may be detrimental to patient care.

PMID- 24670041
TI  - Fiber diffraction of the prion-forming domain HET-s(218-289) shows dehydration
      induced deformation of a complex amyloid structure.
AB  - Amyloids are filamentous protein aggregates that can be formed by many different
      proteins and are associated with both disease and biological functions. The
      pathogenicities or biological functions of amyloids are determined by their
      particular molecular structures, making accurate structural models a requirement
      for understanding their biological effects. One potential factor that can affect
      amyloid structures is hydration. Previous studies of simple stacked beta-sheet
      amyloids have suggested that dehydration does not impact structure, but other
      studies indicated dehydration-related structural changes of a putative water
      filled nanotube. Our results show that dehydration significantly affects the
      molecular structure of the fungal prion-forming domain HET-s(218-289), which
      forms a beta-solenoid with no internal solvent-accessible regions. The
      dehydration-related structural deformation of HET-s(218-289) indicates that water
      can play a significant role in complex amyloid structures, even when no obvious
      water-accessible cavities are present. 

PMID- 24670042
TI  - Immobilization of Piromyces rhizinflata beta-glucanase on poly(dimethylsiloxane)
      and Si wafer and prediction of optimum reaction for enzyme activity.
AB  - EglA, a beta-1,4-glucanase isolated from the ruminal fungus Piromyces
      rhizinflata, shows promise in a wide range of industrial applications because of
      its broad substrate specificity. In this study, EglA was immobilized on different
      supporting materials including poly(dimethylsiloxane) (PDMS), Si wafer, textured
      Si wafer, and indium tin oxide-coated (ITO-coated) glass. The binding abilities
      of PDMS and Si wafer toward EglA were significantly higher than those of the
      other supporting materials. The optimized temperature and pH conditions for EglA
      immobilized on PDMS and on Si wafer were further determined by a response surface
      methodology (RSM) combined with a central composite design (CCD). The results
      indicated that the optimum pH and temperature values as well as the specific beta
      glucanase activity of EglA on PDMS were higher than those of free-form EglA. In
      addition, EglA immobilized on PDMS could be reused up to six times with
      detectable enzyme activity, while the enzyme activity of Eg1A on Si wafer was
      undetectable after three cycles of enzyme reaction. The results demonstrate that
      PDMS is an attractive supporting material for EglA immobilization and could be
      developed into an enzyme chip or enzyme tube for potential industrial
      applications. 

PMID- 24670044
TI  - Electrocatalytic water oxidation by a monomeric amidate-ligated Fe(III)-aqua
      complex.
AB  - The six-coordinate Fe(III)-aqua complex [Fe(III)(dpaq)(H2O)](2+) (1, dpaq is 2
      [bis(pyridine-2-ylmethyl)]amino-N-quinolin-8-yl-acetamido) is an electrocatalyst
      for water oxidation in propylene carbonate-water mixtures. An electrochemical
      kinetics study has revealed that water oxidation occurs by oxidation to
      Fe(V)(O)(2+) followed by a reaction first order in catalyst and added water,
      respectively, with ko = 0.035(4) M(-1) s(-1) by the single-site mechanism found
      previously for Ru and Ir water oxidation catalysts. Sustained water oxidation
      catalysis occurs at a high surface area electrode to give O2 through at least 29
      turnovers over an 15 h electrolysis period with a 45% Faradaic yield and no
      observable decomposition of the catalyst. 

PMID- 24670045
TI  - Ambient mass spectrometry imaging: plasma assisted laser desorption ionization
      mass spectrometry imaging and its applications.
AB  - Mass spectrometry imaging (MSI) has been widely used in many research areas for
      the advantages of providing informative molecular distribution with high
      specificity. Among the recent progress, ambient MSI has attracted increasing
      interests owing to its characteristics of ambient, in situ, and nonpretreatment
      analysis. Here, we are presenting the ambient MSI for traditional Chinese
      medicines (TCMs) and authentication of work of art and documents using plasma
      assisted laser desorption ionization mass spectrometry (PALDI-MS). Compared with
      current ambient MSI methods, an excellent average resolution of 60 MUm * 60 MUm
      pixel size was achieved using this system. The feasibility of PALDI-based MSI was
      confirmed by seal imaging, and its authentication applications were demonstrated
      by imaging of printed Chinese characters. Imaging of the Radix Scutellariae slice
      showed that the two active components, baicalein and wogonin, mainly were
      distributed in the epidermis of the root, which proposed an approach for
      distinguishing TCMs' origins and the distribution of active components of TCMs
      and exploring the environmental effects of plant growth. PALDI-MS imaging
      provides a strong complement for the MSI strategy with the enhanced spatial
      resolution, which is promising in many research fields, such as artwork
      identification, TCMs' and botanic research, pharmaceutical applications, etc. 

PMID- 24670043
TI  - Inflammation and pancreatic cancer: molecular and functional interactions between
      S100A8, S100A9, NT-S100A8 and TGFbeta1.
AB  - BACKGROUND: In order to gain further insight on the crosstalk between pancreatic
      cancer (PDAC) and stromal cells, we investigated interactions occurring between
      TGFbeta1 and the inflammatory proteins S100A8, S100A9 and NT-S100A8, a PDAC
      associated S100A8 derived peptide, in cell signaling, intracellular calcium
      (Cai2+) and epithelial to mesenchymal transition (EMT). NF-kappaB, Akt and mTOR
      pathways, Cai2+ and EMT were studied in well (Capan1 and BxPC3) and poorly
      differentiated (Panc1 and MiaPaCa2) cell lines. RESULTS: NT-S100A8, one of the
      low molecular weight N-terminal peptides from S100A8 to be released by PDAC
      derived proteases, shared many effects on NF-kappaB, Akt and mTOR signaling with
      S100A8, but mainly with TGFbeta1. The chief effects of S100A8, S100A9 and NT
      S100A8 were to inhibit NF-kappaB and stimulate mTOR; the molecules inhibited Akt
      in Smad4-expressing, while stimulated Akt in Smad4 negative cells. By restoring
      Smad4 expression in BxPC3 and silencing it in MiaPaCa2, S100A8 and NT-S100A8 were
      shown to inhibit NF-kappaB and Akt in the presence of an intact TGFbeta1
      canonical signaling pathway. TGFbeta1 counteracted S100A8, S100A9 and NT-S100A8
      effects in Smad4 expressing, not in Smad4 negative cells, while it synergized
      with NT-S100A8 in altering Cai2+ and stimulating PDAC cell growth. The effects of
      TGFbeta1 on both EMT (increased Twist and decreased N-Cadherin expression) and
      Cai2+ were antagonized by S100A9, which formed heterodimers with TGFbeta1 (MALDI
      TOF/MS and co-immuno-precipitation). CONCLUSIONS: The effects of S100A8 and
      S100A9 on PDAC cell signaling appear to be cell-type and context dependent. NT
      S100A8 mimics the effects of TGFbeta1 on cell signaling, and the formation of
      complexes between TGFbeta1 with S100A9 appears to be the molecular mechanism
      underlying the reciprocal antagonism of these molecules on cell signaling, Cai2+
      and EMT.

PMID- 24670046
TI  - Surviving two hours of ventricular fibrillation in accidental hypothermia.
AB  - BACKGROUND: Cardiac arrest as a consequence of deep accidental hypothermia is
      associated with high mortality. Standardized prehospital management as well as
      rewarming with extracorporeal circulation (ECC) are important factors to improve
      survival. The objective of this case report is to illustrate the importance of
      effective cardiopulmonary resuscitation (CPR) and ECC in a cardiac arrest
      following deep accidental hypothermia. CASE REPORT: A 42-year-old man was found
      unresponsive to external stimuli and pulseless at an outdoor temperature of 1
      degrees C. CPR was started at the scene by laypersons, and the emergency medical
      services (EMS) arrived 5 minutes after the emergency call. Resuscitation
      according to International Liaison Committee on Resuscitation (ILCOR) guidelines
      was initiated by EMS. The first recorded rhythm was ventricular fibrillation
      (VF), which persisted, despite repeated defibrillation. The patient showed signs
      of severe hypothermia and, during ongoing CPR, was transported to hospital where
      on arrival the patient's rectal temperature was measured at 22 degrees C.
      Resuscitation measures were continued and warming was started at the emergency
      room. Due to persistent VF and deep hypothermia, the patient was transferred to a
      cardiothoracic surgical unit for rewarming with ECC. At commencement of ECC, CPR
      had been going for approximately 130 minutes and a total of 38 defibrillations
      had been made. During this time interval the patients was pulseless. At a core
      temperature of 30 degrees C, one defibrillation restored sinus rhythm and
      subsequently stable circulation was achieved. The patient received a further 24
      hours of hypothermia treatment at 32-34 degrees C. He was discharged to
      rehabilitation facilities after 3 weeks of hospital care. Three months after the
      cardiac arrest the patient was fully recovered, was back to work, and had resumed
      normal activities. CONCLUSIONS: We demonstrate a case of cardiac arrest due to
      deep accidental hypothermia that stresses the importance of effective CPR and
      early-stage consideration of the use of ECC for safe and effective rewarming.

PMID- 24670047
TI  - The influence of short-term firefighting activity on information processing
      performance.
AB  - This study examined the following: effects of simulated firefighting (FF)
      activities under heat stress on sustained attention; whether incident
      rehabilitation (IR) influences performance; and relationships between
      performance, affect and personality. Firefighters performed ~18 min of FF.
      Attention, physiological, perceptual and psychological assessments were made
      before and after FF, IR and recovery. IR had no effects. Self-rated Energy
      increased, Tiredness decreased and Anxiety increased immediately post-FF; all
      returned to baseline 120 min post. The immediate effect of FF was faster reaction
      time (RT) followed by slowing after recovery. Perceived Energy at baseline was
      associated (p-values < 0.05) with faster and Tiredness with slower post-FF RTs;
      Accuracy was unaffected. Conscientiousness was negatively associated with RT
      before and 120 min following FF. RTs were faster following FF, accuracy was
      unchanged. Higher baseline Energy/lower Tiredness were associated with faster,
      less variable RTs at baseline and post-FF. Those with higher Conscientiousness
      had faster RTs. Research should further investigate higher-level cognitive
      processing following, or ideally during, FF.

PMID- 24670048
TI  - Verbal learning in the context of background music: no influence of vocals and
      instrumentals on verbal learning.
AB  - BACKGROUND: Whether listening to background music enhances verbal learning
      performance is still a matter of dispute. In this study we investigated the
      influence of vocal and instrumental background music on verbal learning. METHODS:
      226 subjects were randomly assigned to one of five groups (one control group and
      4 experimental groups). All participants were exposed to a verbal learning task.
      One group served as control group while the 4 further groups served as
      experimental groups. The control group learned without background music while the
      4 experimental groups were exposed to vocal or instrumental musical pieces during
      learning with different subjective intensity and valence. Thus, we employed 4
      music listening conditions (vocal music with high intensity: VOC_HIGH, vocal
      music with low intensity: VOC_LOW, instrumental music with high intensity:
      INST_HIGH, instrumental music with low intensity: INST_LOW) and one control
      condition (CONT) during which the subjects learned the word lists. Since it
      turned out that the high and low intensity groups did not differ in terms of the
      rated intensity during the main experiment these groups were lumped together.
      Thus, we worked with 3 groups: one control group and two groups, which were
      exposed to background music (vocal and instrumental) during verbal learning. As
      dependent variable, the number of learned words was used. Here we measured
      immediate recall during five learning sessions (recall 1 - recall 5) and delayed
      recall for 15 minutes (recall 6) and 14 days (recall 7) after the last learning
      session. RESULTS: Verbal learning improved during the first 5 recall sessions
      without any strong difference between the control and experimental groups. Also
      the delayed recalls were similar for the three groups. There was only a trend for
      attenuated verbal learning for the group passively listened to vocals. This
      learning attenuation diminished during the following learning sessions.
      CONCLUSIONS: The exposure to vocal or instrumental background music during
      encoding did not influence verbal learning. We suggest that the participants are
      easily able to cope with this background stimulation by ignoring this information
      channel in order to focus on the verbal learning task.

PMID- 24670049
TI  - Organocatalytic entry into 2,6-disubstituted aza-Achmatowicz piperidinones:
      application to (-)-sedacryptine and its epimer.
AB  - Enantiomerically pure 2,6-disubstituted piperidinones were synthesized from
      furfural involving an organocatalyzed Mannich reaction, aza-Achmatowicz reaction,
      and an N-acyliminium ion-mediated coupling step. This approach was also
      successfully applied to a total synthesis of (-)-sedacryptine and one of its
      epimers. 

PMID- 24670050
TI  - Effects of socioeconomic position and clinical risk factors on spontaneous and
      iatrogenic preterm birth.
AB  - BACKGROUND: The literature shows a variable and inconsistent relationship between
      socioeconomic position and preterm birth. We examined risk factors for
      spontaneous and iatrogenic preterm birth, with a focus on socioeconomic position
      and clinical risk factors, in order to explain the observed inconsistency.
      METHODS: We carried out a retrospective population-based cohort study of all
      singleton deliveries in Nova Scotia from 1988 to 2003. Data were obtained from
      the Nova Scotia Atlee Perinatal Database and the federal income tax T1 Family
      Files. Separate logistic models were used to quantify the association between
      socioeconomic position, clinical risk factors and spontaneous preterm birth and
      iatrogenic preterm birth. RESULTS: The study population included 132,714
      singleton deliveries and the rate of preterm birth was 5.5%. Preterm birth rates
      were significantly higher among the women in the lowest (versus the highest)
      family income group for spontaneous (rate ratio 1.14, 95% confidence interval
      (CI) 1.03, 1.25) but not iatrogenic preterm birth (rate ratio 0.95, 95% CI 0.75,
      1.19). Adjustment for maternal characteristics attenuated the family income
      spontaneous preterm birth relationship but strengthened the relationship with
      iatrogenic preterm birth. Clinical risk factors such as hypertension were
      differentially associated with spontaneous (rate ratio 3.92, 95% CI 3.47, 4.44)
      and iatrogenic preterm (rate ratio 14.1, 95% CI 11.4, 17.4) but factors such as
      diabetes mellitus were not (rate ratio 4.38, 95% CI 3.21, 5.99 for spontaneous
      and 4.02, 95% CI 2.07, 7.80 for iatrogenic preterm birth). CONCLUSIONS:
      Socioeconomic position and clinical risk factors have different effects on
      spontaneous and iatrogenic preterm. Recent temporal increases in iatrogenic
      preterm birth appear to be responsible for the inconsistent relationship between
      socioeconomic position and preterm birth.

PMID- 24670051
TI  - Identification of the potential risk factors for monoclonal gammopathy of
      undetermined significance of progression.
AB  - BACKGROUNDS: Monoclonal gammopathy of undetermined significance (MGUS) is a
      premalignant plasma cell disorder. The etiology of MGUS progression remains
      unclear and is a current topic of investigation. METHODS: This review summarizes
      the essential features of MGUS and the potential risk factors for MGUS of
      progression. RESULTS: Many clinical studies have been conducted to identify the
      critical risk markers that play important roles in progression. Some clinical
      variables, such as immunophenotypic markers and cytogenetic changes, have been
      recognized as potential risk factors. CONCLUSIONS: In this review, we discuss
      novel insights from recent studies of potential risk factors, and we propose
      future directions for clinical management and additional studies.

PMID- 24670052
TI  - Importance of ABCC1 for cancer therapy and prognosis.
AB  - Multidrug resistance presents one of the most important causes of cancer
      treatment failure. Numerous in vitro and in vivo data have made it clear that
      multidrug resistance is frequently caused by enhanced expression of ATP-binding
      cassette (ABC) transporters. ABC transporters are membrane-bound proteins
      involved in cellular defense mechanisms, namely, in outward transport of
      xenobiotics and physiological substrates. Their function thus prevents toxicity
      as carcinogenesis on one hand but may contribute to the resistance of tumor cells
      to a number of drugs including chemotherapeutics on the other. Within 48 members
      of the human ABC superfamily there are several multidrug resistance-associated
      transporters. Due to the well documented susceptibility of numerous drugs to
      efflux via ABC transporters it is highly desirable to assess the status of ABC
      transporters for individualization of treatment by their substrates. The
      multidrug resistance associated protein 1 (MRP1) encoded by ABCC1 gene is one of
      the most studied ABC transporters. Despite the fact that its structure and
      functions have already been explored in detail, there are significant gaps in
      knowledge which preclude clinical applications. Tissue-specific patterns of
      expression and broad genetic variability make ABCC1/MRP1 an optimal candidate for
      use as a marker or member of multi-marker panel for prediction of chemotherapy
      resistance. The purpose of this review was to summarize investigations about
      associations of gene and protein expression and genetic variability with
      prognosis and therapy outcome of major cancers. Major advances in the knowledge
      have been identified and future research directions are highlighted.

PMID- 24670053
TI  - Modeling competitive adsorption of mixtures of volatile organic compounds in a
      fixed-bed of beaded activated carbon.
AB  - A two-dimensional mathematical model was developed to study competitive
      adsorption of n-component mixtures in a fixed-bed adsorber. The model consists of
      an isotherm equation to predict adsorption equilibria of n-component volatile
      organic compounds (VOCs) mixture from single component isotherm data, and a
      dynamic adsorption model, the macroscopic mass, energy and momentum conservation
      equations, to simulate the competitive adsorption of the n-components onto a
      fixed-bed of adsorbent. The model was validated with experimentally measured data
      of competitive adsorption of binary and eight-component VOCs mixtures onto beaded
      activated carbon (BAC). The mean relative absolute error (MRAE) was used to
      compare the modeled and measured breakthrough profiles as well as the amounts of
      adsorbates adsorbed. For the binary and eight-component mixtures, the MRAE of the
      breakthrough profiles was 13 and 12%, respectively, whereas, the MRAE of the
      adsorbed amounts was 1 and 2%, respectively. These data show that the model
      provides accurate prediction of competitive adsorption of multicomponent VOCs
      mixtures and the competitive adsorption isotherm equation is able to accurately
      predict equilibrium adsorption of VOCs mixtures. 

PMID- 24670054
TI  - MRI diagnosis of ovarian fibrothecomas: tumour appearances and oestrogenic effect
      features.
AB  - OBJECTIVE: To study MRI diagnosis of ovarian fibrothecomas. METHODS: MRI
      appearances of 27 ovarian fibrothecomas 26 female patients confirmed by surgical
      pathology were retrospectively reviewed and correlated with clinical and
      histological findings. RESULTS: Most patients were post-menopausal females 73.1%
      (19/26) of cases. 38.5% (10/26) of patients showed an elevated serum carbohydrate
      antigen 125 (CA-125) level (>35 U ml(-1)). On MR T2 weighted imaging, 3 distinct
      features were revealed. (1) Homogeneous hypointense masses in 25.9% (7/27) cases.
      (2) Heterogeneous tumours with mostly isointense and few patchy hyperintense
      areas in 51.9% (14/27) cases. (3) Heterogeneous tumours with predominantly
      hyperintense and few isointense parts in 22.2% (6/27) cases. On T1 weighted
      imaging, all the fibrothecomas turned out to be homogeneous masses except six
      cystic degeneration cases. After contrast, 70.4% (19/27) tumours showed
      homogeneous mild enhancement in all phases. Beyond the tumours, endometrial
      abnormality and uterus enlargement were found in 38.5% (10/26) and 15.4% (4/26)
      patients, respectively. Ascites were seen in 53.8% (14/26) patients. There was a
      statistically significant difference among the 3 T2 weighted image features (F =
      7.024; p = 0.003) in terms of the size of fibrothecomas. The cystic tumours also
      had the tendency to show the ascite condition (p = 0.002) as well as elevated
      serum CA-125 levels (p = 0.014). Vimentin was positively stained in 10 (76.9%) of
      13 cases who underwent the immunohistochemical analysis. CONCLUSION: MRI has the
      superiority to show the distinct appearances of tumours as well as their
      functional features according to oestrogenic effect. ADVANCES IN KNOWLEDGE: This
      study describes the unique features of fibrothecomas on MRI on a relatively large
      series of patients with tumours and the indirect oestrogenic effect findings.

PMID- 24670055
TI  - Myomatous hepatic angiomyolipoma: imaging findings in 14 cases with radiological
      pathological correlation and review of the literature.
AB  - OBJECTIVE: To display and analyse the imaging features of myomatous hepatic
      angiomyolipomas (MHAMLs). METHODS: The imaging features (CT = 9; MRI = 10;
      ultrasound = 10; contrast-enhanced ultrasound = 4) of 14 patients with
      pathologically proven MHAMLs were reviewed retrospectively. RESULTS: MHAMLs were
      surgically resected in the 14 patients (10 females and 4 males; age, 27-64 years;
      mean, 45 years), all of whom had negative hepatitis markers and were positive for
      the immunohistochemical stain homatropine methylbromide-45. The tumours were
      solitary and well defined, and ranged in size from 1.9 to 9.1 cm (mean, 5.7 cm).
      On dynamic contrast-enhanced CT, MRI and ultrasound scans, all tumours showed
      fast strong enhancement in the arterial phase and moderate washout in the portal
      venous and delayed phases, and the greater portions of the tumours were slightly
      lower than the surrounding hepatic parenchyma. In some cases, a small area of
      prolonged or increasing enhancement in the tumour was recognized in the delayed
      phase. Early draining vessels to the portal vein or hepatic vein could be seen in
      some cases. However, no capsular signs could be confidently identified in the
      delayed phase. Haemorrhagic cavities were recognized in two cases, and nodular
      low-intensity areas in the tumours on T2 weighted imaging that showed slow and
      faint enhancement on dynamic scans were seen in two cases. However, no necrosis
      was identified. CONCLUSION: Dynamic enhanced imaging studies revealed some
      specific features of MHAMLs that distinguish them from other hypervascular
      hepatic tumours, especially when combined with clinical features. Familiarity
      with imaging and clinical features of MHAMLs could avoid unnecessary surgical
      resection of these generally benign tumours. ADVANCES IN KNOWLEDGE: This article
      systematically describes the imaging features of MHAMLs.

PMID- 24670057
TI  - Inositol phosphates induce DAPI fluorescence shift.
AB  - The polymer inorganic polyP (polyphosphate) and inositol phosphates, such as IP6
      (inositol hexakisphosphate; also known as phytic acid), share many biophysical
      features. These similarities must be attributed to the phosphate groups present
      in these molecules. Given the ability of polyP to modify the excitation-emission
      spectra of DAPI we decided to investigate whether inositol phosphates possess the
      same property. We discovered that DAPI-IP6 complexes emit at approximately 550 nm
      when excited with light of wavelength 410-420 nm. IP5 (inositol
      pentakisphosphate) is also able to induce a similar shift in DAPI fluorescence.
      Conversely, IP3 (inositol trisphosphate) and IP4 (inositol tetrakisphosphate) are
      unable to shift DAPI fluorescence. We have employed this newly discovered feature
      of DAPI to study the enzymatic activity of the inositol polyphosphate multikinase
      and to monitor phytase phosphatase reactions. Finally, we used DAPI-IP6
      fluorescence to determine the amount of IP6 in plant seeds. Using an IP6 standard
      curve this straight-forward analysis revealed that among the samples tested,
      borlotti beans possess the highest level of IP6 (9.4 mg/g of dry mass), whereas
      the Indian urad bean the lowest (3.2 mg/g of dry mass). The newly identified
      fluorescence properties of the DAPI-IP5 and DAPI-IP6 complexes allow the levels
      and enzymatic conversion of these two important messengers to be rapidly and
      reliably monitored.

PMID- 24670056
TI  - De novo transcriptome analysis of Hevea brasiliensis tissues by RNA-seq and
      screening for molecular markers.
AB  - BACKGROUND: The rubber tree, Hevea brasiliensis, is a species native to the
      Brazilian Amazon region and it supplies almost all the world's natural rubber, a
      strategic raw material for a variety of products. One of the major challenges for
      developing rubber tree plantations is adapting the plant to biotic and abiotic
      stress. Transcriptome analysis is one of the main approaches for identifying the
      complete set of active genes in a cell or tissue for a specific developmental
      stage or physiological condition. RESULTS: Here, we report on the sequencing,
      assembling, annotation and screening for molecular markers from a pool of H.
      brasiliensis tissues. A total of 17,166 contigs were successfully annotated.
      Then, 2,191 Single Nucleotide Variation (SNV) and 1.397 Simple Sequence Repeat
      (SSR) loci were discriminated from the sequences. From 306 putative, mainly non
      synonymous SNVs located in CDS sequences, 191 were checked for their ability to
      characterize 23 Hevea genotypes by an allele-specific amplification technology.
      For 172 (90%), the nucleotide variation at the predicted genomic location was
      confirmed, thus validating the different steps from sequencing to the in silico
      detection of the SNVs. CONCLUSIONS: This is the first study of the H.
      brasiliensis transcriptome, covering a wide range of tissues and organs, leading
      to the production of the first developed SNP markers. This process could be
      amplified to a larger set of in silico detected SNVs in expressed genes in order
      to increase the marker density in available and future genetic maps. The results
      obtained in this study will contribute to the H. brasiliensis genetic breeding
      program focused on improving of disease resistance and latex yield.

PMID- 24670058
TI  - Glutathione-capped gold nanoclusters as photosensitizers. Visible light-induced
      hydrogen generation in neutral water.
AB  - Glutathione-capped metal nanoclusters (Aux-GSH NCs) which exhibit molecular-like
      properties are employed as a photosensitizer for hydrogen generation in a
      photoelectrochemical cell (PEC) and a photocatalytic slurry reactor. The
      reversible reduction (E(0) = -0.63 V vs RHE) and oxidation (E(0) = 0.97 and 1.51
      V vs RHE) potentials of these metal nanoclusters make them suitable for driving
      the water-splitting reaction. When a mesoscopic TiO2 film sensitized by Aux-GSH
      NCs is used as the photoanode with a Pt counter electrode in aqueous buffer
      solution (pH = 7), we observe significant photocurrent activity under visible
      light (400-500 nm) excitation. Additionally, sensitizing Pt/TiO2 nanoparticles
      with Aux-GSH NCs in an aqueous slurry system and irradiating with visible light
      produce H2 at a rate of 0.3 mmol of hydrogen/h/g of Aux-GSH NCs. The rate of H2
      evolution is significantly enhanced (~5 times) when a sacrificial donor, such as
      EDTA, is introduced into the system. Using metal nanoclusters as a
      photosensitizer for hydrogen generation lays the foundation for the future
      exploration of other metal nanoclusters with well-controlled numbers of metal
      atoms and capping ligands. 

PMID- 24670061
TI  - Decisional Support Algorithm for Collaborative Care Planning using the
      Participation and Environment Measure for Children and Youth (PEM-CY): A Mixed
      Methods Study.
AB  - ABSTRACT Aims: The purpose of this study was to explore the utility of the
      Participation and Environment Measure for Children and Youth (PEM-CY) for
      collaborative care planning with parents of children with disabilities. Methods:
      An explanatory sequential mixed methods approach was employed to examine how
      community-based service providers interpret and apply PEM-CY case results to set
      goals and formulate care plans with parents. We used two distinct, interactive
      phases that included collection and summary of PEM-CY data in Phase One
      (quantitative) and sequential collection and analysis of interview data during
      Phase Two (qualitative). Twenty-three parents of children with disabilities (mean
      age = 10.7 years) completed the PEM-CY community section during Phase One (quan).
      Four PEM-CY case reports were used with seven providers who were interviewed
      during Phase Two (QUAL). Results: Providers identified a four-step decisional
      support algorithm for leveraging PEM-CY case results in care planning: (1) parent
      rank orders activities in which change is desired, (2) child preferences are
      incorporated, (3) provider clarifies parent and child goals, and (4) activity
      specific supports, barriers, and strategies are identified. Conclusions: Further
      validation and refinement of the decisional support algorithm with parents and
      children when applied to PEM-CY home and school reports is discussed.

PMID- 24670059
TI  - Prevalence and risk factors of kidney disease in urban Karachi: baseline findings
      from a community cohort study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is being increasingly recognized as a
      leading public health problem. However, there are limited data available with
      respect to prevalence of CKD in Pakistan, a developing South Asian country. The
      study presents the baseline findings of prevalence and risk factors for adult
      kidney disease in a Pakistani community cohort. METHODS: A total of 667
      households were enrolled between March 2010 and August 2011 including 461 adults,
      aged 15 and older. Mild kidney disease was defined as estimated Glomerular
      Filtration Rate (eGFR) >=60 ml/min with microalbuminuria >= 30 mg/dl and moderate
      kidney disease was defined as eGFR <60 ml/min (with or without microalbuminuria).
      RESULTS: The overall prevalence of kidney disease was 16.6% with 8.6%
      participants having mild kidney disease and 8% having moderate kidney disease.
      Age was significantly associated with kidney disease (p < 0.0001). The frequency
      of diabetes, hypertension and smoking differed significantly among the three
      groups, i.e., no kidney disease, mild kidney disease and moderate kidney disease.
      CONCLUSION: Our study results suggest that the burden of kidney disease in this
      population is found considerable and comparable to neighboring developing
      countries. We believe that these results have critical implications on health and
      economics of these countries and due to the epidemic of diabetes, hypertension,
      cardiovascular disease, smoking and association with worsening poverty, further
      rapid growth is expected. There is an urgent need for early recognition and
      prevention strategies based on risk factors and disease trends determined through
      longitudinal research.

PMID- 24670060
TI  - Bioprospecting for acidophilic lipid-rich green microalgae isolated from
      abandoned mine site water bodies.
AB  - With fossil fuel sources in limited supply, microalgae show tremendous promise as
      a carbon neutral source of biofuel. Current microalgae biofuel strategies
      typically rely on growing high-lipid producing laboratory strains of microalgae
      in open raceways or closed system photobioreactors. Unfortunately, these
      microalgae species are found to be sensitive to environmental stresses or
      competition by regional strains. Contamination by invasive species can diminish
      productivity of commercial algal processes. A potential improvement to current
      strategies is to identify high-lipid producing microalgae, which thrive in
      selected culture conditions that reduce the risk of contamination, such as low
      pH. Here we report the identification of a novel high-lipid producing microalgae
      which can tolerate low pH growth conditions. Lig 290 is a Scenedesmus spp.
      isolated from a low pH waterbody (pH = 4.5) in proximity to an abandoned lignite
      mine in Northern Ontario, Canada. Compared to a laboratory strain of Scendesmus
      dimorphus, Lig 290 demonstrated robust growth rates, a strong growth profile, and
      high lipid production. As a consequence, Lig 290 may have potential application
      as a robust microalgal species for use in biofuel production. 

PMID- 24670062
TI  - Environmental risk factors in the incidence of Johne's disease.
AB  - This review addresses the survival and persistence of Mycobacterium avium subsp.
      paratuberculosis (MAP), the causative pathogen of Johne's disease (JD), once it
      has left its ruminant host. JD has significant economic impact on dairy, beef and
      sheep industries and is difficult to control due to the long-term sub-clinical
      nature of the infection, intermittent or persistent MAP shedding during and after
      this period, inadequate test effectiveness, and the potential for MAP to exist
      for extended periods outside the host. The role that environmental factors play
      in the persistence and spread of MAP and consequent disease is assessed.
      Published risk factor analysis, organism survival across various environmental
      media and conditions, presence and spread in ruminant and non-ruminant wildlife,
      and the general potential for survival and multiplication of MAP ex-host both on
      and off-farm are discussed and knowledge gaps highlighted. An inclusive approach
      to disease management that takes into account the persistence and transport of
      the causative organism in on-farm soils and waters, land use and management,
      dispersal by domestic and non-domestic host species, as well as general animal
      husbandry is required on those farms where more traditional approaches to disease
      management have failed to reduce disease prevalence. 

PMID- 24670064
TI  - Development of solvent-free ambient mass spectrometry for green chemistry
      applications.
AB  - Green chemistry minimizes chemical process hazards in many ways, including
      eliminating traditional solvents or using alternative recyclable solvents such as
      ionic liquids. This concept is now adopted in this study for monitoring solvent
      free reactions and analysis of ionic liquids, solids, and catalysts by mass
      spectrometry (MS), without using any solvent. In our approach, probe electrospray
      ionization (PESI), an ambient ionization method, was employed for this purpose.
      Neat viscous room-temperature ionic liquids (RTILs) in trace amounts (e.g., 25
      nL) could be directly analyzed without sample carryover effect, thereby enabling
      high-throughput analysis. With the probe being heated, it can also ionize ionic
      solid compounds such as organometallic complexes as well as a variety of neat
      neutral solid chemicals (e.g., amines). More importantly, moisture-sensitive
      samples (e.g., [bmim][AlCl4]) can be successfully ionized. Furthermore, detection
      of organometallic catalysts (including air-sensitive [Rh-MeDuPHOS][OTf]) in ionic
      liquids, a traditionally challenging task due to strong ion suppression effect
      from ionic liquids, can be enabled using PESI. In addition, PESI can be an ideal
      approach for monitoring solvent-free reactions. Using PESI-MS, we successfully
      examined the alkylation of amines by alcohols, the conversion of pyrylium into
      pyridinium, and the condensation of aldehydes with indoles as well as air- and
      moisture-sensitive reactions such as the oxidation of ferrocene and the
      condensation of pyrazoles with borohydride. Interestingly, besides the expected
      reaction products, the reaction intermediates such as the monopyrazolylborate ion
      were also observed, providing insightful information for reaction mechanisms. We
      believe that the presented solvent-free PESI-MS method would impact the green
      chemistry field. 

PMID- 24670063
TI  - A model for the flexibility of the distal histidine in dehaloperoxidase
      hemoglobin A based on X-ray crystal structures of the carbon monoxide adduct.
AB  - Dehaloperoxidase hemoglobin A (DHP A) is a multifunctional hemoglobin that
      appears to have evolved oxidative pathways for the degradation of xenobiotics as
      a protective function that complements the oxygen transport function. DHP A
      possesses at least two internal binding sites, one for substrates and one for
      inhibitors, which include various halogenated phenols and indoles. Herein, we
      report the X-ray crystallographic structure of the carbonmonoxy complex (DHPCO).
      Unlike other DHP structures with 6-coordinated heme, the conformation of the
      distal histidine (H55) in DHPCO is primarily external or solvent exposed, despite
      the fact that the heme Fe is 6-coordinated. As observed generally in globins, DHP
      exhibits two distal histidine conformations (one internal and one external). In
      previous structural studies, we have shown that the distribution of H55
      conformations is weighted strongly toward the external position when the DHP heme
      Fe is 5-coordinated. The large population of the external conformation of the
      distal histidine observed in DHPCO crystals at pH 6.0 indicates that some
      structural factor in DHP must account for the difference from other globins,
      which exhibit a significant external conformation only when pH < 4.5. While the
      original hypothesis suggested that interaction with a heme-Fe-bound ligand was
      the determinant of H55 conformation, the current study forces a refinement of
      that hypothesis. The external or open conformation of H55 is observed to have
      interactions with two propionate groups in heme, at distances of 3.82 and 2.73 A,
      respectively. A relatively weak hydrogen bonding interaction between H55 and CO,
      combined with strong interactions with heme propionate (position 6), is
      hypothesized to strengthen the external conformation of H55. Density function
      theory (DFT) calculations were conducted to test whether there is a weaker
      hydrogen bond interaction between H55 and heme bonded CO or O2. Molecular
      dynamics simulations were conducted to examine how the tautomeric forms of H55
      affect the dynamic motions of the distal histidine that govern the switching
      between open and closed conformations. The calculations support the modified
      hypothesis suggesting a competition between the strength of interactions with
      heme ligand and the heme propionates as the factors that determine the
      conformation of the distal histidine. 

PMID- 24670065
TI  - Elements of effective palliative care models: a rapid review.
AB  - BACKGROUND: Population ageing, changes to the profiles of life-limiting illnesses
      and evolving societal attitudes prompt a critical evaluation of models of
      palliative care. We set out to identify evidence-based models of palliative care
      to inform policy reform in Australia. METHOD: A rapid review of electronic
      databases and the grey literature was undertaken over an eight week period in
      April-June 2012. We included policy documents and comparative studies from
      countries within the Organisation for Economic Co-operation and Development
      (OECD) published in English since 2001. Meta-analysis was planned where >1 study
      met criteria; otherwise, synthesis was narrative using methods described by Popay
      et al. (2006). RESULTS: Of 1,959 peer-reviewed articles, 23 reported systematic
      reviews, 9 additional RCTs and 34 non-randomised comparative studies. Variation
      in the content of models, contexts in which these were implemented and lack of
      detailed reporting meant that elements of models constituted a more meaningful
      unit of analysis than models themselves. Case management was the element most
      consistently reported in models for which comparative studies provided evidence
      for effectiveness. Essential attributes of population-based palliative care
      models identified by policy and addressed by more than one element were
      communication and coordination between providers (including primary care), skill
      enhancement, and capacity to respond rapidly to individuals' changing needs and
      preferences over time. CONCLUSION: Models of palliative care should integrate
      specialist expertise with primary and community care services and enable
      transitions across settings, including residential aged care. The increasing
      complexity of care needs, services, interventions and contextual drivers warrants
      future research aimed at elucidating the interactions between different
      components and the roles played by patient, provider and health system factors.
      The findings of this review are limited by its rapid methodology and focus on
      model elements relevant to Australia's health system.

PMID- 24670066
TI  - Non-overlapping functions of Nck1 and Nck2 adaptor proteins in T cell activation.
AB  - BACKGROUND: Signalling by the T cell antigen receptor (TCR) results in the
      activation of T lymphocytes. Nck1 and Nck2 are two highly related adaptor
      proteins downstream of the TCR that each contains three SH3 and one SH2 domains.
      Their individual functions and the roles of their SH3 domains in human T cells
      remain mostly unknown. RESULTS: Using specific shRNA we down-regulated the
      expression of Nck1 or Nck2 to approximately 10% each in Jurkat T cells. We found
      that down-regulation of Nck1 impaired TCR-induced phosphorylation of the kinases
      Erk and MEK, activation of the AP-1 and NFAT transcription factors and
      subsequently, IL-2 and CD69 expression. In sharp contrast, down-regulation of
      Nck2 hardly impacts these activation read-outs. Thus, in contrast to Nck2, Nck1
      is a positive regulator for TCR-induced stimulation of the Erk pathway. Mutation
      of the third SH3 domain of Nck1 showed that this domain was required for this
      activity. Further, TCR-induced NFAT activity was reduced in both Nck1 and Nck2
      knock-down cells, showing that both isoforms are involved in NFAT activation.
      Lastly, we show that neither Nck isoform is upstream of p38 phosphorylation or
      Ca2+influx. CONCLUSIONS: In conclusion, Nck1 and Nck2 have non-redundant roles in
      human T cell activation in contrast to murine T cells.

PMID- 24670067
TI  - The cost of lost productivity due to premature cancer-related mortality: an
      economic measure of the cancer burden.
AB  - BACKGROUND: Most measures of the cancer burden take a public health perspective.
      Cancer also has a significant economic impact on society. To assess this economic
      burden, we estimated years of potential productive life lost (YPPLL) and costs of
      lost productivity due to premature cancer-related mortality in Ireland. METHODS:
      All cancers combined and the 10 sites accounting for most deaths in men and in
      women were considered. To compute YPPLL, deaths in 5-year age-bands between 15
      and 64 years were multiplied by average working-life expectancy. Valuation of
      costs, using the human capital approach, involved multiplying YPPLL by age-and
      gender specific gross wages, and adjusting for unemployment and workforce
      participation. Sensitivity analyses were conducted around retirement age and wage
      growth, labour force participation, employment and discount rates, and to explore
      the impact of including household production and caring costs. Costs were
      expressed in ?2009. RESULTS: Total YPPLL was lower in men than women (men =
      10,873; women = 12,119). Premature cancer-related mortality costs were higher in
      men (men: total cost = ?332 million, cost/death = ?290,172, cost/YPPLL = ?30,558;
      women: total cost = ?177 million, cost/death = ?159,959, cost/YPPLL = ?14,628).
      Lung cancer had the highest premature mortality cost (?84.0 million; 16.5% of
      total costs), followed by cancers of the colorectum (?49.6 million; 9.7%), breast
      (?49.4 million; 9.7%) and brain & CNS (?42.4 million: 8.3%). The total economic
      cost of premature cancer-related mortality in Ireland amounted to ?509.5 million
      or 0.3% of gross domestic product. An increase of one year in the retirement age
      increased the total all-cancer premature mortality cost by 9.9% for men and 5.9%
      for women. The inclusion of household production and caring costs increased the
      total cost to ?945.7 million. CONCLUSION: Lost productivity costs due to cancer
      related premature mortality are significant. The higher premature mortality cost
      in males than females reflects higher wages and rates of workforce participation.
      Productivity costs provide an alternative perspective on the cancer burden on
      society and may inform cancer control policy decisions.

PMID- 24670068
TI  - Motivational interviewing interventions and alcohol abuse among college students:
      a systematic review.
AB  - OBJECTIVE: The study sought to assess the effectiveness of Motivational
      Interviewing (MI) interventions in reducing alcohol consumption among college
      students, as compared to no intervention or alternative interventions. It also
      sought to identify the potential moderators to MI intervention effects. DATA
      SOURCE: Database sources consulted included Cochrane Central Register of Control
      Trials, PsycINFO, PsycARTICLE, PsycLIT, CINAHL, and MEDLINE. STUDY INCLUSION AND
      EXCLUSION CRITERIA: Included studies were (1) underpinned by experimental, quasi
      experimental, and nonexperimental designs; (2) studies in which participants were
      either college males only or females only or both; and (3) studies in which
      adaptations of MI were based on key MI principles. Excluded studies were (1) non
      English language studies; (2) studies not published from 2000-2012; (3) studies
      in which participants were not college students; (4) studies in which
      intervention was not delivered by face-to-face approach; and (5) studies that
      failed to embark on postintervention follow-ups. DATA EXTRACTION: A total of 115
      abstracts were screened. These were narrowed down to 13 studies from which data
      for the study were extracted. DATA SYNTHESIS: Selected studies were underpinned
      by experimental, quasi-experimental, and nonexperimental designs. Owing to the
      heterogeneity in selected studies, a narrative synthesis was used. RESULTS: MI
      interventions were found to be effective in reducing alcohol consumption among
      college students, when compared to alternative interventions or no intervention.
      Potential moderators of MI intervention effects were identified to include
      practitioner's adherence to MI techniques and individual's drinking motives.
      CONCLUSION: MI presents itself as a promising tool that can augment the many
      existing social-environmental strategies of health promotion.

PMID- 24670070
TI  - The Healthy Workplace Project: results of a hygiene-based approach to employee
      wellness.
AB  - PURPOSE: An employee wellness program was evaluated to assess changes in germ
      transmission, absenteeism, and cost of infection-related illness among office
      based employees. DESIGN: One-group pretest-posttest design, with intervention
      delivered for 90 days and measurement conducted over 1 year. SETTING: Employees
      of a large office space in Georgia. SUBJECTS: One thousand six hundred forty-five
      employees. INTERVENTION: The Healthy Workplace Project is a 90-day wellness
      program aimed to increase health and productivity of employees through
      educational and engagement activities focusing on improving awareness,
      recognizing infection-related illnesses, and reducing the spread of germs in the
      workplace. MEASURES: Three types of data were collected: (1) bacterial audits
      through use of adenosine triphosphate monitoring of various work spaces; (2) self
      report absenteeism data using the World Health Organization's Health and Work
      Performance Questionnaire; and (3) participant employees' medical claims/costs of
      infection-related minor illnesses. ANALYSIS: Frequencies and bacterial audit
      data; Wilcoxon signed ranks tests to determine changes in rates on absenteeism
      and health care costs. RESULTS: Bacterial audits demonstrated a reduction in
      contamination levels of 33% across all measured spaces. Absenteeism rates were
      reduced by 13%. Medical service utilization costs were not significantly reduced
      for individual employees over the project year. CONCLUSION: Educational
      strategies and individual monitoring of germ transmission appears effective in
      improving employees' health and decreasing absenteeism.

PMID- 24670069
TI  - Validity of self-reported fitness across black and white race, gender, and health
      literacy subgroups.
AB  - PURPOSE: To compare concurrent criterion validity of the Self-Reported Fitness
      (SRFit) Survey, a new fitness measure, between black and white race, gender, and
      health literacy groups. DESIGN: Cross-sectional. SETTING: Midwest urban primary
      care center and commercial fitness center. SUBJECTS: One hundred one black,
      white, male, and female primary care patients aged >=40 years. MEASURES: Measures
      included demographics, the Rapid Estimate of Adult Literacy in Medicine, the
      SRFit Survey, and the Rikli and Jones Senior Fitness Test battery of physical
      tests. The BodPod determined percentage of body fat. Body mass index was
      calculated. ANALYSIS: Concurrent validity was assessed using Pearson and Spearman
      rank order correlations between corresponding physical tests and SRFit survey
      items. RESULTS: Correlations between physical tests and SRFit items ranged from r
      = .52 to .76 (rho = .41-.85) in males, r = .40 to .79 (rho = .33-.80) in females,
      r = .45 to .79 (rho = .53-.82) in blacks, and r = .49 to .77 (rho = .33-.82) in
      whites. Correlations were r = .58 (rho = .58) to r = .77 (rho = .79) in persons
      with low health literacy and r = .50 to .79 (rho = .39-.85) among persons with
      moderate to high health literacy. CONCLUSION: SRFit shows similar concurrent
      validity across race, gender, and health literacy subgroups.

PMID- 24670071
TI  - Encoded exposure to tobacco use in social media predicts subsequent smoking
      behavior.
AB  - PURPOSE: Assessing the potential link between smoking behavior and exposure to
      mass media depictions of smoking on social networking Web sites. DESIGN: A
      representative longitudinal panel of 200 young adults in Connecticut. SETTING:
      Telephone surveys were conducted by using computer assisted telephone
      interviewing technology and electronic dialing for random digit dialing and
      listed samples. SUBJECTS: Connecticut residents aged 18 to 24 years. MEASURES: To
      measure encoded exposure, respondents were asked whether or not they had smoked a
      cigarette in the past 30 days and about how often they had seen tobacco use on
      television, in movies, and in social media content. Respondents were also asked
      about cigarette use in the past 30 days, and a series of additional questions
      that have been shown to be predictive of tobacco use. ANALYSIS: Logistic
      regression was used to test for our main prediction that reported exposure to
      social media tobacco depictions at time 1 would influence time 2 smoking
      behavior. RESULTS: Encoded exposure to social media tobacco depictions (B = .47,
      p < .05) was a significant predictor of time 2 smoking, even after controlling
      for all the aforementioned predictors. CONCLUSION: Our results suggest that
      social media depictions of tobacco use predict future smoking tendency, over and
      above the influence of TV and movie depictions of smoking. This is the first
      known study to specifically assess the role of social media in informing tobacco
      behavior.

PMID- 24670072
TI  - Promoting changes in obesogenic behaviors: does coworker social support play a
      role?
AB  - PURPOSE: To examine the association between worksite social support and changes
      in diet, physical activity, and body mass index (BMI). DESIGN: Cohort analysis of
      an underlying randomized, controlled weight gain prevention worksite trial:
      Promoting Activity and Changes in Eating. SETTING: The trial occurred in the
      greater Seattle area. SUBJECTS: Baseline and follow-up data were obtained on a
      nested cohort of employees (n = 958-1078) from 33 small- to medium-sized
      worksites. MEASURES: Worksite social support, diet, physical activity, and BMI
      measures were assessed using a self-reported questionnaire. ANALYSIS: To adjust
      for multilevel data and multiple time points, we used generalized estimating
      equations and logistic mixed models. RESULTS: Higher baseline worksite social
      support was associated with greater changes in fruit and vegetable intake (p =
      .001; summary food-frequency questions). CONCLUSION: This study does not support
      a conclusive relationship between worksite social support and health behavior
      change.

PMID- 24670073
TI  - A qualitative study of recruitment barriers, motivators, and community-based
      strategies for increasing clinical trials participation among rural and urban
      populations.
AB  - PURPOSE: Participation in clinical trials (CTs) is low among rural communities.
      Investigators report difficulty recruiting rural individuals for CTs. The study
      purpose was to identify recruitment barriers, motivators, and strategies to help
      increase access to and participation in CTs in rural and urban communities.
      APPROACH: Qualitative focus groups/interviews. SETTING: Rural and urban counties
      in one southeastern state. PARTICIPANTS: Two hundred twelve African-American and
      white men and women ages 21+. METHOD: Nineteen focus groups and nine interviews
      were conducted. Audio files were transcribed and organized into NVivo10.
      Recurring themes were examined by geographic location. RESULTS: Although similar
      barriers, motivators, and strategies were reported by urban and rural groups,
      perceptions regarding their importance varied. Recruitment barriers mentioned in
      both rural and urban groups included fear, side effects, limited understanding,
      limited time, and mistrust. Rural groups were more mindful of time commitment
      involved. Both rural and urban participants reported financial incentives as the
      top motivator to CT participation, followed by personal illness (urban groups)
      and benefits to family (rural groups). Recruitment strategies suggested by rural
      participants involved working with schools/churches and using word of mouth,
      whereas partnering with schools, word of mouth, and media were recommended most
      by urban groups. CONCLUSION: Perceived recruitment barriers, motivators, and
      strategies did not differ considerably between rural and urban groups. Major
      barriers identified by participants should be addressed in future CT recruitment
      and education efforts. Findings can inform recruitment and communication
      strategies for reaching both urban and rural communities.

PMID- 24670074
TI  - Point-of-Decision Signs and Stair Use in a University Worksite Setting: General
      Versus Specific Messages.
AB  - PURPOSE: This study tested the effectiveness of two point-of-decision signs to
      increase stair use and investigated message content by comparing signs with
      general and specific messages. DESIGN: This study used a quasi-experimental time
      series design, including a 2-week baseline period: 2 weeks with a general message
      and 2 weeks with a specific message. SETTING: The signs were placed in an eight
      story university building. SUBJECTS: The subjects comprised all adults entering
      the building. During the study, 2997 observations of stair/elevator choice were
      made. INTERVENTION: A stair-prompt sign with a general message and a sign with a
      specific message served as the interventions. MEASURES: Observers measured
      stair/elevator choice, demographics, and traffic volume. ANALYSIS: Logistic
      regression analyses were employed, adjusting for covariates. RESULTS: The
      specific sign intervention showed significantly increased odds of stair use
      compared to baseline (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.46
      2.84). The odds of stair use were also significantly greater with the specific
      sign than the general sign (OR = 1.57, 95% CI = 1.13-2.20). CONCLUSION: Only the
      specific sign significantly increased stair use. The results indicate that a
      specific message may be more effective at promoting stair use.

PMID- 24670075
TI  - Exploratory and confirmatory factor analyses and demographic correlate models of
      the strategies for weight management measure for overweight or obese adults.
AB  - PURPOSE: There is a need for a self-report measure that assesses use of
      recommended strategies related to weight management. DESIGN: Cross-sectional
      analysis. SETTING: Universities, community. SUBJECTS: Exploratory factor analysis
      (EFA) involved data from 404 overweight/obese young adults (mean age = 22 years,
      48% non-Hispanic white, 68% ethnic minority). Confirmatory factor analysis (CFA)
      involved data from 236 overweight/obese adults (mean age = 42 years, 63% non
      Hispanic white, 84% ethnic minority). MEASURES: The Strategies for Weight
      Management (SWM) measure is a 35-item questionnaire that assesses use of
      recommended behavioral strategies for reducing energy intake and increasing
      energy expenditure in overweight/obese adults. ANALYSIS: EFA and CFA were
      conducted on the SWM. Correlate models assessed the associations between SWM
      factor/total scores and demographics by using linear regressions. RESULTS: EFA
      suggested a four-factor model: strategies categorized as targeting (1) energy
      intake, (2) energy expenditure, (3) self-monitoring, and (4) self-regulation. CFA
      indicated good model fit (chi(2)/df = 2.0, comparative fit index = .90,
      standardized root mean square residual = .06, and root mean square error of
      approximation = .07, confidence interval = .06-.08, R(2) = .11-.74). The fourth
      factor had the lowest loadings, possibly because the items cover a wide domain.
      The final model included 20 items. Correlate models revealed weak associations
      between the SWM scores and age, gender, Hispanic ethnicity, and relationship
      status in both samples, with the models explaining only 1% to 8% of the variance
      (betas = -.04 to .29, p < .05). CONCLUSION: The SWM has promising psychometric
      qualities in two diverse samples.

PMID- 24670076
TI  - Direct C-H bond arylation of (benzo)oxazoles with aryl chlorides catalyzed by N
      heterocyclic carbene-palladium(II)-1-methylimidazole complex.
AB  - The direct C-H bond arylation of (benzo)oxazoles with aryl chlorides was achieved
      catalyzed by a well-defined NHC-Pd(II)-Im complex. Under the optimal conditions,
      various aryl chlorides were successfully applied as the arylating reagents to
      achieve the 2-aryl (benzo)oxazoles in acceptable to high yields, providing a
      convenient and alternative method for the direct C-H bond arylation of
      (benzo)oxazoles and enriching the chemistry of the NHC-Pd(II) complex in organic
      synthesis. 

PMID- 24670077
TI  - A new furanoxanthone from Garcinia mangostana.
AB  - Our phytochemical study on the stem bark of Garcinia mangostana has led to the
      discovery of a new furanoxanthone, mangaxanthone A (1), together with five known
      analogs. The five known analogs that were isolated are alpha-mangostin (2), beta
      mangostin (3), cowagarcinone B (4), and dulcisxanthone F (5). The structural
      elucidations of these compounds were carried out by interpreting their
      spectroscopic data, mainly 1D and 2D NMR spectra and MS. 

PMID- 24670078
TI  - The effect of a backrest and seatpan inclination on sitting discomfort and trunk
      muscle activation in subjects with extension-related low back pain.
AB  - Few studies have demonstrated that seating modifications reduce low back pain
      (LBP). One recent study found that a forward-inclined seatpan reduced low back
      discomfort (LBD), however this was only examined in people with flexion-related
      LBP. No study has yet investigated its effectiveness among people with extension
      related LBP. This crossover study examined 12 subjects with extension-related
      LBP. Sitting discomfort and surface electromyography of three trunk muscles were
      recorded during a 10-minute typing task while sitting with two different seatpan
      inclinations, both with and without a backrest. LBD (p < 0.001) and overall body
      discomfort (OBD) (p = 0.016) were significantly greater on the forward-inclined
      seatpan. The backrest did not alter trunk muscle activation or sitting
      discomfort. The results demonstrate that in a specific subgroup of people with
      extension-related LBP, increasing forward seatpan inclination significantly
      increased LBD and OBD. Future research should consider matching ergonomics
      prescriptions according to the individual presentation of people with LBP.

PMID- 24670079
TI  - Comparing high altitude treatment with current best care in Dutch children with
      moderate to severe atopic dermatitis (and asthma): study protocol for a pragmatic
      randomized controlled trial (DAVOS trial).
AB  - BACKGROUND: About 10 to 20% of children in West European countries have atopic
      dermatitis (AD), often as part of the atopic syndrome. The full atopic syndrome
      also consists of allergic asthma, allergic rhinitis and food allergy. Treatment
      approaches for atopic dermatitis and asthma include intermittent anti
      inflammatory therapy with corticosteroids, health education and self-management
      training. However, symptoms persist in a subgroup of patients. Several
      observational studies have shown significant improvement in clinical symptoms in
      children and adults with atopic dermatitis or asthma after treatment at high
      altitude, but evidence on the efficacy when compared to treatment at sea level is
      still lacking. METHODS/DESIGN: This study is a pragmatic randomized controlled
      trial for children with moderate to severe AD within the atopic syndrome.
      Patients are eligible for enrolment in the study if they are: diagnosed with
      moderate to severe AD within the atopic syndrome, aged between 8 and 18 years,
      fluent in the Dutch language, have internet access at home, able to use the
      digital patient system Digital Eczema Center Utrecht (DECU), willing and able to
      stay in Davos for a six week treatment period. All data are collected at the
      Wilhelmina Children's Hospital and DECU. Patients are randomized over two groups.
      The first group receives multidisciplinary inpatient treatment during six weeks
      at the Dutch Asthma Center in Davos, Switzerland. The second group receives
      multidisciplinary treatment during six weeks at the outpatient clinic of the
      Wilhelmina Children's Hospital, Utrecht, the Netherlands. The trial is not
      conducted as a blind trial. The trial is designed with three components:
      psychosocial, clinical and translational. Primary outcomes are coping with itch,
      quality of life and disease activity. Secondary outcomes include asthma control,
      medication use, parental quality of life, social and emotional wellbeing of the
      child and translational parameters. DISCUSSION: The results of this trial will
      provide evidence for the efficacy of high altitude treatment compared to
      treatment at sea level for children with moderate to severe AD. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN88136485.

PMID- 24670080
TI  - Rituximab (Rituxan) therapy for severe thyroid-associated ophthalmopathy
      diminishes IGF-1R(+) T cells.
AB  - CONTEXT: Rituximab depletes CD20(+) B cells and has shown potential benefit in
      thyroid-associated ophthalmopathy (TAO). The impact of rituximab on T cell
      phenotype in TAO is unexplored. OBJECTIVE: The objective of the study was to
      quantify the abundance of IGF-I receptor-positive (IGF-1R(+)) CD4 and CD8 T cells
      in active TAO before and after treatment with rituximab. DESIGN: This was a
      retrospective case series assessing IGF-1R(+) T cells before and after treatment
      with rituximab with an 18-month follow-up. SETTING: The study was conducted at a
      tertiary care medical center. PATIENTS: Study participants included eight
      patients with severe TAO. INTERVENTIONS: Two infusions of rituximab (1 g or 500
      mg each) were administered 2 weeks apart. MAIN OUTCOME MEASURES: Quantification
      of IGF-1R(+) T cells using flow cytometry was measured. RESULTS: Eight patients
      with moderate to severe TAO [mean pretreatment clinical activity score (CAS) 5.1
      +/- 0.2 (SEM)] were treated. Four to 6 weeks after treatment, CAS improved to 1.5
      +/- 0.3, whereas the proportion of IGF-1R(+) CD3(+) T cells declined from 41.9%
      to 28.3% (P = .004). The proportion of IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) T
      cells declined 4-6 weeks after treatment (from 45.6% to 21.5% and from 32.0% to
      15.8%, P = .003 and P = .001, respectively). In two patients, IGF-1R(+) CD4(+)
      and IGF-1R(+) CD8(+) subsets approximated pretreatment levels after 16 weeks.
      CONCLUSIONS: Frequency of IGF-1R(+) T cells in patients with TAO declines within
      4-6 weeks after rituximab treatment. This phenotypic shift coincides with
      clinical improvement. Thus, assessment of the abundance of IGF-1R(+) T cells in
      response to rituximab may provide a biomarker of clinical response. Our current
      findings further implicate the IGF-1R pathway in the pathogenesis of TAO.

PMID- 24670081
TI  - Associations of sex steroids with bone maturation, bone mineral density, bone
      geometry, and body composition: a cross-sectional study in healthy male
      adolescents.
AB  - BACKGROUND: Although both testosterone (T) and estradiol (E2) are considered
      essential in the regulation of the male skeleton, there are few data concerning
      the relative contribution of T and E2 on bone mineral density (BMD), bone
      geometry, and bone maturation in healthy boys. OBJECTIVE: The objective of the
      study was to analyze the relationship between T and E2 and BMD, bone geometry,
      skeletal maturation, and body composition. METHODS: This is a cross-sectional
      study in 199 healthy boys (aged 6-19 y). T and E2 were determined by liquid
      chromatography tandem mass spectrometry. Whole-body and lumbar areal bone mineral
      density (aBMD) and bone area, lean mass, and fat mass were determined by dual
      energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal
      site) volumetric BMD (vBMD) and bone geometry were assessed at the nondominant
      forearm and leg using peripheral quantitative computed tomography. Skeletal age
      was determined by an X-ray of the left hand. RESULTS: T was positively associated
      with lean mass (P < .001), lumbar and whole-body bone area (P < .001), trabecular
      and cortical area (P < .01), and periosteal circumference (P < .01) at the
      radius. E2 was positively associated with lumbar and whole-body aBMD (P < .001),
      trabecular vBMD at the radius and tibia (P < .01), and cortical thickness at the
      radius (P < .05). E2 was an independent negative predictor of the endosteal
      circumference (P < .01). Moreover, E2 was positively associated with bone age
      advancement (P < .001). CONCLUSION: Circulating E2 is positively associated with
      bone maturation and aBMD and vBMD and negatively with endosteal circumference in
      healthy boys, whereas T is a determinant of lean mass and bone size. These
      findings underscore the important role of E2 in skeletal development in boys.

PMID- 24670082
TI  - Continuous 24-hour leptin, proopiomelanocortin, and amino acid measurements in
      human cerebrospinal fluid: correlations with plasma leptin, soluble leptin
      receptor, and amino acid levels.
AB  - CONTEXT: In order to characterize diurnal changes in central leptin and its
      target neuropeptide, proopiomelanocortin (POMC), we measured leptin and POMC in
      cerebrospinal fluid (CSF) as related to changes in plasma leptin and soluble
      leptin receptor (sOB-R) levels. CSF and plasma levels of 20 amino acids (AA) were
      also measured because AA can affect brain POMC. DESIGN AND PARTICIPANTS: Stored
      CSF and plasma samples obtained from eight healthy subjects who served as
      controls for a previous study were evaluated. CSF was collected hourly over 33 h
      via indwelling subarachnoid catheter. Leptin, sOB-R, and POMC were measured by
      sensitive ELISA and AA by gas chromatography-mass spectrometry. RESULTS: There
      was a diurnal rhythm for plasma leptin with a peak at 2200 h (144% of baseline)
      and there was a similar diurnal rhythm for CSF leptin with a peak (117%) 3-5 h
      after the plasma peak. Plasma sOB-R was lowest at 0300 h and correlated
      negatively with plasma and CSF leptin. A diurnal rhythm for POMC in CSF was also
      detected with a peak (125%) at 0100 h. A positive correlation existed between CSF
      POMC and leptin in individual subjects over time. CSF levels of many AA increased
      at night. There was a significant correlation between CSF POMC and 10 AA,
      including leucine, isoleucine, tryptophan, and tyrosine. CONCLUSIONS: Diurnal
      changes occur in leptin and POMC in human CSF that likely reflect changes in
      central leptin and melanocortin activity. Our results suggest that nocturnal
      elevations in leptin, AA, and POMC may help to suppress appetite and feeding at
      night.

PMID- 24670083
TI  - Circulating vitamin D, supplement use, and cardiovascular disease risk: the MrOS
      Sleep Study.
AB  - CONTEXT: Evidence suggests an inverse association between circulating 25(OH)
      vitamin D and cardiovascular disease (CVD). OBJECTIVE: To determine the
      association between serum 25(OH) vitamin D and risk for CVD events. SETTING AND
      DESIGN: From March 2000 to April 2002, participants were recruited for the
      Osteoporotic Fractures in Men (MrOS) study. Between December 2003 and March 2005,
      members of the MrOS cohort were invited to participate in the MrOS Sleep Study.
      Participants were recruited from 6 clinical centers across the United States and
      followed for a mean of 5.9 years. Three-thousand-one-hundred-thirty-five men ages
      65 and older were included from the MrOS cohort, of whom 116 were excluded for
      missing vitamin D or CVD data. Participants were divided into two groups based on
      serum 25(OH) vitamin D levels, <20 ng/mL and >=20 ng/mL. Participants were
      followed for CVD endpoints including coronary heart disease (CHD) and
      cerebrovascular events. Age- and multivariable-adjusted hazard ratios were
      calculated and stratified by use of vitamin D containing supplements. RESULTS: We
      observed no significant association between circulating 25(OH) vitamin D and risk
      of CVD event (HR, 0.91; 95% confidence interval (CI), 0.73-1.13) and CHD event
      (HR, 0.81; 95% CI, 0.61-1.07). For cerebrovascular events, men with vitamin D
      deficiency exhibited a higher risk (HR, 1.44; 95% CI, 1.00-2.08) using the
      minimally adjusted model and after excluding supplement users (HR, 1.70; 95% CI,
      1.02-2.83). CONCLUSIONS: 25(OH) vitamin D was not associated with risk of CVD and
      CHD events. However, vitamin D deficiency may be associated with an increased
      risk of cerebrovascular events.

PMID- 24670085
TI  - Relationships between 24-hour urinary free cortisol concentrations and metabolic
      syndrome in obese children.
AB  - CONTEXT: Clinical features of Metabolic Syndrome (MetS) and Cushing's Syndrome
      are similar, suggesting a pathogenetic role of hypothalamus-pituitary-adrenal
      axis in MetS. OBJECTIVE: The aim of the study was to determine whether MetS
      diagnosis and specific clusters of MetS components (waist circumference,
      dyslipidemia, hypertension, and impaired glucose metabolism) are associated with
      serum cortisol (SC) or 24-h urinary free cortisol (UFC) levels. DESIGN AND
      SETTING: We conducted cross-sectional analyses of data from our obesity cohort.
      We studied 264 obese children (age, 11.0 +/- 2.8 years; male, 48%; BMI, 28.2 +/-
      5.4 kg/m(2)). We examined UFC, SC, homeostasis model assessment (HOMA), and
      features of MetS (waist circumference, blood pressure, fasting lipids, and
      glucose). RESULTS: Slightly increased UFC concentrations were measured in 30.7%
      of the children. Obese children with MetS had significantly (P = .003) higher UFC
      levels compared with obese children without MetS. Girls demonstrated
      significantly higher UFC concentrations compared with boys independent of
      pubertal stage. UFC and SC levels were significantly related to features of MetS,
      but the associations were stronger for UFC. In multivariate analyses adjusted for
      age, sex, and body mass index, none of the features of MetS but HOMA index was
      correlated with UFC, whereas SC demonstrated no significant association to any
      parameter of MetS or HOMA. CONCLUSIONS: Our findings support the hypothesis that
      changes in the hypothalamus-pituitary-adrenal axis are related to MetS in
      obesity. UFC seems to be a suitable marker for this relationship. Norm values for
      UFC adapted to obese children may help to avoid unnecessary dexamethasone
      suppression tests.

PMID- 24670084
TI  - Clinical utility of simultaneous quantitation of 25-hydroxyvitamin D and 24,25
      dihydroxyvitamin D by LC-MS/MS involving derivatization with DMEQ-TAD.
AB  - CONTEXT: The discovery of hypercalcemic diseases due to loss-of-function
      mutations in 25-hydroxyvitamin D-24-hydroxylase has placed a new demand for
      sensitive and precise assays for 24,25-dihydroxyvitamin D [24,25-(OH)2D].
      OBJECTIVE: We describe a novel liquid chromatography and tandem mass spectrometry
      based method involving derivatization with DMEQ-TAD {4-[2-(6,7-dimethoxy-4-methyl
      3,4-dihydroquinoxalinyl)ethyl]-1,2,4-triazoline-3,5-dione} to simultaneously
      assay multiple vitamin D metabolites including 25-hydroxyvitamin D (25-OH-D) and
      24,25-(OH)2D using 100 MUL of serum with a 5-minute run time. DESIGN: The assay
      uses a newly synthesized internal standard d6-24,25-(OH)2D3 enabling the
      quantitation of 24,25-(OH)2D3 as well as the determination of the ratio of 25-OH
      D3 to 24,25-(OH)2D3, a physiologically useful parameter. SETTING: We report data
      on more than 1000 normal and disease samples involving vitamin D deficiency or
      hypercalcemia in addition to studies involving knockout mouse models. RESULTS:
      The assay showed good correlation with samples from quality assurance schemes for
      25-OH-D (25-OH-D2 and 25-OH-D3) determination (-2% to -5% bias) and exhibited low
      inter- and intraassay coefficients of variation (4%-7%) and lower limits of
      quantitation of 0.25-0.45 nmol/L. In clinical studies, we found a strong
      correlation between serum levels of 25-OH-D3 and 24,25-(OH)2D3 (r(2) = 0.80) in
      subjects over a broad range of 25-OH-D3 values and a marked lack of production of
      24,25-(OH)2D3 below 25 nmol/L of 25-OH-D. The ratio of 25-OH-D3 to 24,25-(OH)2D3,
      which remained less than 25 in vitamin D-sufficient subjects (serum 25-OH-D < 50
      nmol/L) but was greatly elevated (80-100) in patients with idiopathic infantile
      hypercalcemia. CONCLUSIONS: The new method showed good utility in clinical
      settings involving vitamin D deficiency; supplementation with vitamin D and
      idiopathic infantile hypercalcemia, as well as in animal models with ablation of
      selected cytochrome P450-containing enzymes involved in vitamin D metabolism.

PMID- 24670086
TI  - Pancreatic enzyme supplementation improves the incretin hormone response and
      attenuates postprandial glycemia in adolescents with cystic fibrosis: a
      randomized crossover trial.
AB  - CONTEXT: Cystic fibrosis-related diabetes is characterized by postprandial,
      rather than fasting, hyperglycemia. Gastric emptying and the release of the
      incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose dependent
      insulinotropic polypeptide (GIP)] are central to postprandial glycemic control.
      Lipolysis is required for fat to slow gastric emptying and stimulate incretin
      release. OBJECTIVE: We aimed to determine the effect of pancreatic enzyme
      replacement therapy (PERT) on postprandial glycemia in adolescents with cystic
      fibrosis (CF). DESIGN: This was a double-blinded randomized crossover trial.
      Subjects consumed a high-fat pancake, with either PERT (50 000 IU lipase) or
      placebo. Gastric emptying was measured by a breath test and blood sampled
      frequently for plasma blood glucose, insulin, glucagon, GLP-1, and GIP. Data were
      also compared with seven healthy subjects. PARTICIPANTS: Fourteen adolescents
      (13.1 +/- 2.7 y) with pancreatic-insufficient CF and seven healthy age-matched
      controls participated in the study. MAIN OUTCOME MEASURE: Postprandial
      hyperglycemia was measured as peak glucose and area under the curve for blood
      glucose at 240 minutes. RESULTS: CF subjects had postprandial hyperglycemia
      compared with controls (area under the curve, P < .0001). PERT reduced
      postprandial hyperglycemia (P = .0002), slowed gastric emptying (P = .003), and
      normalized GLP-1 and GIP secretion (P < .001 for each) when compared with
      placebo, without affecting insulin. CONCLUSION: In young people with pancreatic
      insufficient CF, PERT markedly attenuates postprandial hyperglycemia by slowing
      gastric emptying and augmenting incretin hormone secretion.

PMID- 24670087
TI  - Switch in FGFR3 and -4 expression profile during human renal development may
      account for transient hypercalcemia in patients with Sotos syndrome due to 5q35
      microdeletions.
AB  - CONTEXT: Sotos syndrome is a rare genetic disorder with a distinct phenotypic
      spectrum including overgrowth and learning difficulties. Here we describe a new
      case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth
      factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia.
      OBJECTIVE: We strove to elucidate the evanescent nature of the observed
      hypercalcemia by studying the ontogenesis of FGFR3 and FGFR4, which are both
      associated with fibroblast growth factor (FGF) 23-mediated mineral homeostasis,
      in the developing human kidney. DESIGN: Quantitative RT-PCR and
      immunohistochemical analyses were used on archival human kidney samples to
      investigate the expression of the FGFR signaling pathway during renal
      development. RESULTS: We demonstrated that renal gene and protein expression of
      both FGFRs increased during fetal development between the gestational ages (GAs)
      of 14-40 weeks. Yet FGFR4 expression increased more rapidly as compared with
      FGFR3 (slope 0.047 vs 0.0075, P = .0018). Moreover, gene and protein expression
      of the essential FGFR coreceptor, Klotho, also increased with a significant
      positive correlation between FGFR and Klotho mRNA expression during renal
      development. Interestingly, we found that perinatal FGFR4 expression (GA 38-40
      wk) was 7-fold higher as compared with FGFR3 (P = .0035), whereas in adult kidney
      tissues, FGFR4 gene expression level was more than 2-fold lower compared with
      FGFR3 (P = .0029), thus identifying a molecular developmental switch of FGFR
      isoforms. CONCLUSION: We propose that the heterozygous FGFR4 deletion, as
      observed in the Sotos syndrome patient, leads to a compromised FGF23 signaling
      during infancy accounting for transient hypercalcemia. These findings represent a
      novel and intriguing view on FGF23 mediated calcium homeostasis.

PMID- 24670088
TI  - An open-label, prospective pilot clinical study of denosumab for severe
      hyperparathyroidism in patients with low bone mass undergoing dialysis.
AB  - CONTEXT: Denosumab is widely used for bone diseases with increased bone
      resorption. Its effectiveness in patients with severe secondary
      hyperparathyroidism on dialysis is unclear. OBJECTIVE: This study aimed to
      evaluate the efficacy and safety of denosumab in patients with severe secondary
      hyperparathyroidism who are on dialysis. DESIGN: This 6-month prospective, open
      labeled study evaluated 12 patients (five women, seven men; mean age 53.5 +/- 3.8
      y). All had intact PTH (iPTH; > 1000 pg/mL), low bone mass (T-score < -1.0 SD),
      and bone pain and were poor surgical candidates. Serum calcium, phosphorus,
      alkaline phosphatase (AP), and iPTH levels were assessed at baseline and every
      month thereafter. Vertebral spine x-rays and bone mineral densities (BMDs)
      (lumbar spine and femoral neck) were assessed at the start and end of the study.
      All patients received denosumab (60 mg), calcitriol, phosphate binders, and
      dialysate calcium that were adjusted according to the biochemistry data. RESULTS:
      The BMD increased in both the femoral neck (mean increase 23.7% +/- 4.0%) and
      lumbar spine (17.1% +/- 2.6%) after 6 months. In the first month, most patients
      had increased iPTH levels, which dramatically decreased from 1702.1 +/- 181.9 to
      518.8 +/- 126.8 pg/mL by the end of the study after increasing the calcitriol
      dose. All patients had significant decreases in AP, calcium * phosphorus, and
      bone pain. Changes in femoral neck BMD correlated only with AP and iPTH levels.
      CONCLUSIONS: Denosumab is effective in restoring bone mass and reducing bone pain
      in patients on dialysis with secondary hyperparathyroidism. It also allows for a
      more aggressive use of calcitriol to control hyperparathyroidism.

PMID- 24670089
TI  - AmrZ is a global transcriptional regulator implicated in iron uptake and
      environmental adaption in P. fluorescens F113.
AB  - BACKGROUND: AmrZ, a RHH transcriptional regulator, regulates motility and
      alginate production in pseudomonads. Expression of amrZ depends on the
      environmental stress sigma factor AlgU. amrZ and algU mutants have been shown to
      be impaired in environmental fitness in different pseudomonads with different
      lifestyles. Considering the importance of AmrZ for the ecological fitness of
      pseudomonads and taking advantage of the full sequencing and annotation of the
      Pseudomonas fluorescens F113 genome, we have carried out a ChIP-seq analysis from
      a pool of eight independent ChIP assays in order to determine the AmrZ binding
      sites and its implication in the regulation of genes involved in environmental
      adaption. RESULTS: 154 enriched regions (AmrZ binding sites) were detected in
      this analysis, being 76% of them located in putative promoter regions. 18 of
      these peaks were validated in an independent ChIP assay by qPCR. The 154 peaks
      were assigned to genes involved in several functional classes such as motility
      and chemotaxis, iron homeostasis, and signal transduction and transcriptional
      regulators, including genes encoding proteins implicated in the turn-over of c
      diGMP. A putative AmrZ binding site was also observed by aligning the 154 regions
      with the MEME software. This motif was present in 75% of the peaks and was
      similar to that described in the amrZ and algD promoters in P. aeruginosa. We
      have analyzed the role of AmrZ in the regulation of iron uptake genes, to find
      that AmrZ represses their expression under iron limiting conditions. CONCLUSIONS:
      The results presented here show that AmrZ is an important global transcriptional
      regulator involved in environmental sensing and adaption. It is also a new
      partner in the complex iron homeostasis regulation.

PMID- 24670090
TI  - Enhanced oral bioavailability of piperine by self-emulsifying drug delivery
      systems: in vitro, in vivo and in situ intestinal permeability studies.
AB  - The main purpose of this work was to develop and evaluate a self-emulsifying drug
      delivery system (SEDDS) of piperine to enhance its solubility and
      bioavailability. The formulation was optimized by solubility test and ternary
      phase diagrams. Then physiochemical properties and in vitro release of SEDDS were
      characterized. In vivo pharmacokinetics study and in situ single-pass intestinal
      perfusion were performed to investigate the effects of SEDDS on the
      bioavailability and intestinal absorption of piperine. The optimized formulation
      was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with
      the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of
      piperine SEDDS were significantly higher than the self-prepared capsules. In vivo
      pharmacokinetic study showed Cmax1, Cmax2 and area under the curve of piperine
      after oral administration of SEDDS in rats were 3.8-, 7.2- and 5.2-fold higher
      than the self-prepared capsules, respectively, and the relative bioavailability
      of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the
      effective permeability and the effective absorption rate values of piperine for
      SEDDS were significantly improved comparing to solutions (p < 0.01). So SEDDS
      formulation could improve the oral bioavailability and intestinal absorption of
      piperine effectively.

PMID- 24670091
TI  - Self-microemulsifying drug delivery system (SMEDDS)--challenges and road ahead.
AB  - Self-microemulsifying drug delivery system (SMEDDS) has emerged as a vital
      strategy to formulate poor water soluble compounds for bioavailability
      enhancement. However, certain limitations are associated with SMEDDS formulations
      which include in vivo drug precipitation, formulation handling issues, limited
      lymphatic uptake, lack of predictive in vitro tests and oxidation of unsaturated
      fatty acids. These limitations restrict their potential usage. Inclusion of
      polymers or precipitation inhibitors within lipid based formulations helps to
      maintain drug supersaturation after dispersion. This, thereby, improves the
      bioavailability and reduces the variability on exposure. Also, formulating solid
      SMEDDS helps to overcome liquid handling and stability problems. Usage of medium
      chain triglycerides (MCT) and suitable antioxidants to minimize oxidation of
      unsaturated fatty acids are few of the steps to overcome the limitations
      associated with SMEDDS. The review discussed here, in detail, the limitations of
      SMEDDS and suitable measures that can be taken to overcome them. 

PMID- 24670092
TI  - Influence of magnesium stearate on the physicochemical and pharmacodynamic
      characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres.
AB  - Effective oral insulin delivery has remained a challenge to the pharmaceutical
      industry. This study was designed to evaluate the effect of magnesium stearate on
      the properties of insulin-loaded Eudragit(r) RL 100 entrapped mucoadhesive
      microspheres. Microspheres containing Eudragit(r) RL 100, insulin, and varying
      concentrations of magnesium stearate (agglomeration-preventing agent) were
      prepared by emulsification-coacervation method and characterized with respect to
      differential scanning calorimetry (DSC), morphology, particle size, loading
      efficiency, mucoadhesive and micromeritics properties. The in vitro release of
      insulin from the microspheres was performed in simulated intestinal fluid (SIF,
      pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the
      plasma glucose level of the alloxan-induced diabetic rats after oral
      administration. Stable, spherical, brownish, mucoadhesive, discrete and free
      flowing insulin-loaded microspheres were formed. While the average particle size
      and mucoadhesiveness of the microspheres increased with an increase in the
      proportion of magnesium stearate, loading efficiency generally decreased. After
      12 h, microspheres prepared with Eudragit(r) RL 100: magnesium stearate ratios of
      15:1, 15:2, 15:3 and 15:4 released 68.20 +/- 1.57, 79.40 +/- 1.52, 76.60 +/- 1.93
      and 70.00 +/- 1.00 (%) of insulin, respectively. Reduction in the blood glucose
      level for the subcutaneously (sc) administered insulin was significantly (p <=
      0.05) higher than for most of the formulations. However, the blood glucose
      reduction effect produced by the orally administered insulin-loaded microspheres
      prepared with four parts of magnesium stearate and fifteen parts of Eudragit(r)
      RL 100 after 12 h was equal to that produced by subcutaneously administered
      insulin solution. The results of this study can suggest that this carrier system
      could be an alternative for the delivery of insulin.

PMID- 24670093
TI  - EGFR-targeted poly(ethylene glycol)-distearoylphosphatidylethanolamine micelle
      loaded with paclitaxel for laryngeal cancer: preparation, characterization and in
      vitro evaluation.
AB  - The objective of this study was to evaluate the potential of using polymeric
      micelles modified with a peptide (termed GE11) ligand of epidermal growth factor
      receptor as the targeted carriers to achieve increased accumulation in laryngeal
      cancer and enhanced intracellular delivery for the encapsulated anticancer drugs.
      Poly (ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) micelles
      containing paclitaxel were prepared via film-hydration method followed by
      investigation of in vitro release of paclitaxel in phosphate-buffered saline. The
      average size of GE11-PEG-DSPE/paclitaxel micelle and mPEG-DSPE/paclitaxel were 35
      +/- 2.8 nm [the polydispersity index (PDI) = 0.207] and 28 +/- 2.1 nm (PDI =
      0.154), respectively. Micelles with or without GE11-modified had similar
      physicochemical properties. Transmission electron microscopy showed that the
      micelles were homogeneous and spherical in shape. Encapsulation efficiency and
      drug loading of the micelle were 74.11 +/- 3.89% and 3.58 +/- 2.82%,
      respectively. The in vitro targeting characteristic of GE11-modified micelles was
      investigated by observing the level of cellular uptake of fluorescent coumarin-6
      loaded micelles on EGFR over-expressed human laryngeal cancer cell line Hep-2 and
      EGFR low-expressed human leukemic cell line U-937. Hep-2 cell proliferation was
      significantly inhibited by GE11-PEG-DSPE/paclitaxel micelle compared to mPEG
      DSPE/paclitaxel micelle and Taxol in vitro. Our results suggested that GE11-PEG
      DSPE micelle could be a promising strategy for enhancing paclitaxel's
      chemotherapeutic effects on EGFR over-expressed cancer cells.

PMID- 24670094
TI  - Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in
      vitro characterization, skin irritation test and comparative clinical study.
AB  - Tretinoin (TRT) is a widely used retinoid for the topical treatment of acne,
      photo-aged skin, psoriasis and skin cancer which makes it a good candidate for
      topical formulation. Yet side effects, like redness, swelling, peeling,
      blistering and, erythema, in addition to its high lipophilicity make this
      challenging. Therefore, the aim of this study was the development of TRT-loaded
      proniosomes to improve the drug efficacy and to increase user acceptability and
      compliance by reducing its side effects. Nine formulae were prepared according to
      3(2) factorial design and were evaluated for their morphology, vesicle size,
      entrapment efficiency (EE %), and% of drug released after 5 h. Hydrogel of the
      candidate formula, N8G (proniosomes prepared with 0.025% TRT, and Span60:
      cholesterol molar ratio of 3:1 and incorporated in 1% carbopol gel) was developed
      and evaluated for skin irritation test and clinical study in acne patients
      compared to marketed product. Candidate formula showed higher efficacy and very
      low irritation potential when compared to marketed product in human volunteers.

PMID- 24670095
TI  - Development of biodegradable polymeric implants of RGD-modified PEG-PAMAM-DOX
      conjugates for long-term intratumoral release.
AB  - CONTEXT: The sustained release implants can be directly implanted in tumor site
      by surgery and are promising for cancer treatment. OBJECTIVE: RGD-modified
      PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by
      acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted
      therapy. In order to enhance tumor retention ability and long-term effect of
      drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co
      glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG)
      as carrier materials. METHODS: The implants were prepared by a simple solvent
      evaporation method. Different formulations with varying ratios of three polymers
      were designed, prepared and evaluated on the basis of viscosity, in vitro release
      and drying time. Furthermore, in vivo biodistribution and antitumor activity of
      the implants were studied in mice with subcutaneous C6 xenografts. RESULTS: The
      optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1%
      PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared
      by the optimized formulation was similar according to the assessment of
      similarity factor f2, and the release curves were fell into three phases,
      including a lag-period, then the second phase which was consistent with zero
      order model followed by a plateau. Data of total DOX remained in implants
      indicated the release were faster in vivo than in vitro. Moreover, intratumoral
      drug amount of RGD-PPCD implants was the highest 45 days after implantation.
      Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity
      compared with PPCD and free DOX implants. DISCUSSION AND CONCLUSION: This paper
      presents an exploratory research on macromolecule-drug conjugates, including RGD
      PPCD and PPCD, which have the potential to be developed into long-term effect
      implants for tumor therapy with high efficiency and low systematic toxicity.

PMID- 24670096
TI  - Design, development and characterization of buccal bioadhesive films of Doxepin
      for treatment of odontalgia.
AB  - Tricyclic antidepressants, as doxepin hydrochloride (DH), may have analgesic
      local effect due to its biochemical mechanism of action. Delivery of DH directly
      to the oral cavity could be an interesting alternative for toothache due to its
      analgesic local effect. One problem associated with the mucosal administration
      routes is the short residence time of the dosage form on the mucosal membranes.
      In this sense, we have developed new doxepin mucoadhesive films able of reducing
      pain and increasing the effectiveness of treatment. For this purpose, we tested
      three different polymers: chitosan, sodium hydroxypropylmethylcellulose (HPMC)
      and sodium carboxymethylcellulose (SCMC) in film elaboration. The results
      obtained show that all films are hydrophilic matrices that absorb water when
      placed in an aqueous media. All the films hydrated very quickly, reaching high
      percentage of swelling after just few minutes (5 min for SCMC, 2 min for HPMC and
      30 min for chitosan). Moreover, the SCMC and HPMC films were dissolved whereas
      chitosan was not dissolved. Dissolution also leads to viscous liquids with a
      higher retention time over mucosal surfaces what may lead to adhesive
      interactions. In vitro permeation studies showed that for all the formulations
      studied, SCMC (19.91%), HPMC (69.5%) and chitosan (24.17%), the percentage of
      drug permeated increased compared to the drug solution (8.26%). Specifically the
      HPMC film presents greater amounts of doxepin permeated (49.27 +/- 4.47
      ug/cm(2)).

PMID- 24670097
TI  - Rational formulation strategy from drug discovery profiling to human proof of
      concept.
AB  - The objective of this paper is to introduce some strategic guidance to a rational
      formulation strategy of new molecules as oral dosage forms, based on a sound
      scientific understanding of factors determining the oral bioavailability. The
      critical implication of permeability and solubility is discussed along with the
      efficient dose of the drug. The concept of dose-solubility number is introduced
      as a tool for chemists to assess the develop-ability of different molecules very
      early during discovery stage. Based on this understanding, a rational formulation
      strategy for preclinical and early clinical phases is provided. The technical
      considerations and limitations of different formulation technologies are
      discussed and illustrated via concrete examples. This approach has the advantage
      of streamlining the formulation process in order to avoid delaying the
      development of new drugs due to formulation related issues. 

PMID- 24670098
TI  - Formulation and characterization of albumin microspheres containing
      norcantharidate for liver tumor targeting.
AB  - The objectives of this study were first to encapsulate norcantharidate into
      albumin microspheres by the emulsion crosslinking method and second to
      characterize the microspheres in terms of the morphological examination, particle
      size, and encapsulation efficiency. The in vitro release of norcantharidate from
      the microspheres was studied by using the dialysis bag method. Pharmacokinetics
      and biodistribution studies were used to evaluate the advantages of microspheres
      than the conventional formulations. The microspheres prepared by crosslink
      emulsion were with uniform size, smooth surface, spherical shape, and disperse
      evenly. The particle size was uniform (13.3 +/- 0.4 um) and the encapsulation
      efficiency was 54.3 +/- 4.18%. In vitro release indicated that the
      norcantharidate microspheres had a well-sustained release efficacy and fitted
      Korsmeyer's Peppas release model. In vivo studies showed that pharmacokinetics of
      norcantharidate microspheres could be described by the model of two-compartment
      after i.v. administration and had higher AUC inside liver and spleen than the
      injection group. No histological change occurred to the rat liver after the
      administration of norcantharidate microspheres.

PMID- 24670100
TI  - Enhanced skin permeation of 6-methoxy-2-naphthylacetic acid by salt formation.
AB  - The aim of this work was to prepare salts of 6-methoxy-2-naphthylacetic acid (6
      MNA) to improve its physicochemical properties for percutaneous application. 6
      MNA, an active metabolite of non-steroidal anti-inflammatory drug nabumetone has
      long half life and has the tendency to penetrate well into synovial fluid. The
      physicochemical properties of 6-MNA salts were investigated by solubility
      measurements, differential scanning calorimetry (DSC) and infrared (IR). The DSC
      thermograms and Fourier transform infrared (FT-IR) spectra indicated that 6-MNA
      formed salts with organic and alkali metal bases. Among the series, salts formed
      with amine bases (ethanolamine, diethanolamine, triethanolamine and diethylamine)
      had lower melting points while alkali metal salt (sodium) had higher melting
      point than 6-MNA. The salts had higher solubilities than 6-MNA as determined in
      phosphate buffer at pH 5.0 and 7.4. There is no significant difference in
      partition coefficient (log P) values between salts and 6-MNA at pH 5.0 but, at pH
      7.4, the log P values for the salts increased by 4-10 times as compared to 6-MNA.
      In vitro permeation studies showed that all the salts increased the flux in
      comparision to 6-MNA, and the ethanolamine salt (1b) was found to be having 7.7
      and 9.4 times higher permeability as compared to 6-MNA at pH 5.0 and 7.4,
      respectively.

PMID- 24670099
TI  - Nanostructured lipid (NLCs) carriers as a bioavailability enhancement tool for
      oral administration.
AB  - CONTEXT: Nanostructured lipid carrier (NLCs) is the second generation solid lipid
      nanoparticles (NPs) made up of physiological, biocompatible, biodegradable, non
      sensitizing and non-irritating lipids. OBJECTIVE: The main objective of this
      review is to explore the role of NLCs system for delivering drugs by oral route
      and thus increasing the oral bioavailability. METHODS: The present review article
      highlights the definition and types of NLCs and their importance as colloidal
      carriers including the production techniques and their formulation. This review
      article also deals with the fate of lipids used in the NLCs formulation and the
      NLCs toxicity. CONCLUSION: On the basis of the literature survey done, it was
      concluded that the NLCs enhances the oral bioavailability of the drug and may
      decrease the side effects and toxicity of the lipids used in other polymeric NPs
      as NLCs uses physiological and biodegradable lipids.

PMID- 24670101
TI  - Electron transfer to covalently immobilized Keggin polyoxotungstates on gold.
AB  - Spontaneously adsorbed monolayers have been formed on gold electrodes using a
      Keggin polyoxotungstate with covalently attached alkanethiol linkers of two
      different lengths. Films of both polyoxotungstates show two well-defined
      reduction processes associated with the polyoxotungstate centers where the ionic
      liquid, [BMIM][BF4], acts as supporting electrolyte. The surface coverages are
      both less than that expected for a close-packed monolayer. For the short and long
      linkers, the voltammetric response can be described in terms of the Butler-Volmer
      response involving a surface confined species using standard heterogeneous
      electron transfer rate constants of 170 and 140 s(-1) for the first reduction and
      150 and 100 s(-1) for the second reduction processes, respectively. The rate of
      electron transfer to a solution phase redox probe, ferrocyanide, is significantly
      more sensitive to the length of the linker than the rate of electron transfer to
      the tungstate centers. This behavior probably arises due to potential-induced
      changes in the film structure. 

PMID- 24670102
TI  - Effects of personality on overtime work: a cross-sectional pilot study among
      Japanese white-collar workers.
AB  - BACKGROUND: As detailed associations between personality and long work hours are
      unclear, we assessed associations between personality dimensions and overtime
      work among Japanese white-collar workers. METHODS: From records of hours worked
      over 12 months by 267 office workers in an organization within the service
      industry, average overtime work hours per month and occurrence of excessive
      overtime was determined for each worker. Excessive overtime was defined as >  45
      overtime work hours per month for at least one month. Responses to a
      questionnaire assessing socio-demographic and workplace-related factors and the
      Big Five personality test were analyzed. Associations between personality factors
      and overtime work were assessed by multivariate logistic regression analysis.
      RESULTS: Low Extraversion was associated with excessive overtime work (OR 2.02,
      95%CI 1.02 - 4.02, P =  0.04). CONCLUSIONS: It is suggested that workers with low
      Extraversion can't share work when busy to avoid excessive overtime. Personality
      factors should be considered in studies evaluating work time. Moreover,
      strengthening communication among workers with low Extraversion may reduce
      excessive overtime work and associated health problems.

PMID- 24670103
TI  - Novel, mercury-free synthetic pathway for trifluoromethylthio-substituted
      metallocenes.
AB  - A novel synthetic pathway for trifluoromethylthioferrocene (3), which does not
      involve the use of toxic mercury(II)-based reagents, is described. The novel
      approach involves first the treatment of the commercially available
      bromoferrocene (1a) with NaSCN in the presence of copper(+I) to yield
      thiocyanatoferrocene (1), and then the reaction of 1 with the Rupper-Prakash
      reagent and tetrabutylammonium fluoride (TBAF) to give 3 in an overall yield of
      60%. This approach could be extended for the preparation of thiocyanato-(4) and
      trifluoromethylthio-ruthenocene (7), which are herein both reported for the first
      time. Interestingly, diferrocenyl disulfide (2a) and diruthenocenyl disulfide (5)
      could be isolated as side-products during the synthesis of 3 and 7, respectively.
      All new compounds were unambiguously characterized by (1)H, (13)C, and (19)F NMR
      spectroscopy, mass spectrometry, cyclic voltammetry, elemental analysis, as well
      by X-ray crystallography for 1, 4, 4b, 5, 6, and 7. 1-7 were further tested for
      their toxic activity on cervical cancer (HeLa) and noncancerous (MRC-5) cell
      lines. All organometallic compounds were found either to be nontoxic or to have a
      moderate toxicity toward the cell lines used in this study. 

PMID- 24670104
TI  - When does relational information influence evaluative conditioning?
AB  - Building on the intriguing findings of Peters and Gawronski (2011, Experiment 3),
      we examined the conditions under which relational information (i.e., information
      about how two stimuli are related) moderates evaluative conditioning (EC; i.e.,
      the effect of stimulus pairing on liking). In Experiment 1, participants saw
      stimulus pairs that consisted of a novel nonword (conditioned stimulus; CS) and a
      known positive or negative word (unconditioned stimulus; US). Before or after the
      pairings, participants were told that the nonword had the opposite meaning to the
      word with which it was paired. Subsequent measures of the implicit evaluation of
      the nonwords revealed that nonwords paired with positive words were liked less
      than nonwords paired with negative words, but only when the relational
      information was presented before the CS-US pairings. In a second experiment,
      participants were first informed that the CS and US of each pair were related in
      one way (e.g., that they have the same meaning). Afterwards, this information was
      either confirmed (e.g., that they indeed have the same meaning) or reversed
      (e.g., that they actually have an opposite meaning). Whereas the first relational
      information had more impact on implicit evaluations than on explicit evaluations,
      the reverse was true for the second relational information. Moreover, informing
      participants that CS and US were equivalent produced the same effects as pairing
      CS and US without providing explicit relational information, thus suggesting that
      the mere co-occurrence of CS and US is treated as a cue for equivalence of CS and
      US. Implications for mental process models of EC are discussed. 

PMID- 24670105
TI  - Relationships between body image, nutritional supplement use, and attitudes
      towards doping in sport among adolescent boys: implications for prevention
      programs.
AB  - BACKGROUND: Reports of high levels of use of protein powders and nutritional
      supplements among young men is a concern because these substances may act as a
      gateway for the use of drugs and illegal substances to enhance appearance or
      sports performance. The aim of this study was to investigate the relationship
      between body dissatisfaction, weight change behaviors, supplement use, and
      attitudes towards doping in sport among an adolescent male sample. METHODS:
      Participants were 1148 male adolescents (age range 11-21 years) in Australia who
      completed a self-report questionnaire that measured weight change behaviors,
      supplement use, body dissatisfaction (Male Body Attitudes Scale; MBAS) and
      attitudes towards doping in sport (Performance Enhancing Attitudes Survey; PEAS).
      RESULTS: There was a positive correlation between MBAS total and PEAS scores (r =
      .19, p < .001), indicating that the young men who were more dissatisfied with
      their bodies were more likely to support the use of doping in sport. Young men
      who were currently attempting weight loss or weight gain, and those currently
      consuming energy drinks (etap2 = .01, p < .01) and vitamin/mineral supplements
      (etap2 = .01, p < .01) were also significantly more supportive of doping in
      sport. However, those involved in weight lifting, and using protein powders were
      not (p > .05). CONCLUSIONS: These findings suggest that body dissatisfaction,
      weight change behaviors, and supplement use are related to more lenient attitudes
      towards doping in sport among adolescent boys. Future research might examine
      whether combining educational content for the prevention of body dissatisfaction
      and the use of drugs in sport may have a greater preventive impact than current
      programs aimed at young men.

PMID- 24670106
TI  - Straightforward synthesis of oligopyrroles through a regioselective S(N)Ar
      reaction of pyrroles and halogenated boron dipyrrins.
AB  - A novel stepwise and regioselective nucleophilic aromatic substitution (SNAr)
      reaction of halogenated boron dipyrrins (BODIPYs) with pyrroles has been
      developed under mild conditions with no catalyst needed and shown to be diversity
      oriented. The resultant pyrrole-substituted BODIPYs are interesting red and near
      infrared (NIR) fluorescent dyes with absorption maxima up to 733 nm. Removal of
      the BF2 protecting group of the 3-pyrrole or 3,5-dipyrrole-substituted BODIPYs
      provides a facial entry to oligopyrroles with direct 2,2'-bipyrrole linkages. 

PMID- 24670107
TI  - Tailoring alphabetical metamaterials in optical frequency: plasmonic coupling,
      dispersion, and sensing.
AB  - Tailoring optical properties of artificial metamaterials, whose optical
      properties go beyond the limitations of conventional and naturally occurring
      materials, is of importance in fundamental research and has led to many important
      applications such as security imaging, invisible cloak, negative refraction,
      ultrasensitive sensing, and transformable and switchable optics. Herein, by
      precisely controlling the size, symmetry, and topology of alphabetical
      metamaterials with U, S, Y, H, U-bar, and V shapes, we have obtained highly
      tunable optical response covering visible-to-infrared (vis-NIR) optical
      frequency. In addition, we show a detailed study on the physical origin of
      resonance modes, plasmonic coupling, the dispersion of resonance modes, and the
      possibility of negative refraction. We have found that all the electronic and
      magnetic modes follow the dispersion of surface plasmon polaritons; thus,
      essentially they are electronic- and magnetic-surface-plasmon-polaritons-like
      (ESPP-like and MSPP-like) modes resulted from diffraction coupling between
      localized surface plasmon and freely propagating light. On the basis of the fill
      factor and formula of magnetism permeability, we predict that the alphabetical
      metamaterials should show the negative refraction capability in visible optical
      frequency. Furthermore, we have demonstrated the specific ultrasensitive surface
      enhanced Raman spectroscopy (SERS) sensing of monolayer molecules and femtomolar
      food contaminants by tuning their resonance to match the laser wavelength, or by
      tuning the laser wavelength to match the plasmon resonance of metamaterials. Our
      tunable alphabetical metamaterials provide a generic platform to study the
      electromagnetic properties of metamaterials and explore the novel applications in
      optical frequency. 

PMID- 24670108
TI  - Abdominal obesity and serum adiponectin complexes among population-based
      elementary school children in Japan: a cross-sectional study.
AB  - BACKGROUND: There are a limited number of studies regarding the association
      between abdominal obesity and serum adiponectin complexes (high, medium, and low
      molecular weight adiponectins) among population-based elementary school children,
      especially in Japan, where blood collection is not usually performed during
      annual health examinations of school children. The aim of the present study was
      to investigate the relationship between abdominal obesity and serum adiponectin
      complexes among population-based elementary school children in Japan. METHODS:
      Subjects were all the fourth-grade school children (9 or 10 years of age) in the
      town of Ina during 2005-2008 (N = 1675). The height, weight, percent body fat,
      and waist circumference (WC) of each subject were measured. Blood samples were
      drawn from subjects to measure adiponectin isoform values. Childhood abdominal
      obesity was defined as "a waist-to-height ratio greater than or equal to 0.5" or
      "a WC greater than or equal to 75 cm". The Wilcoxon rank-sum test and the
      logistic regression model were used to analyze the association between abdominal
      obesity and each adiponectin isoform value. RESULTS: Data from 1654 subjects (846
      boys and 808 girls) were analyzed. Adiponectin complexes were lower in the
      abdominal obesity group than in the non-abdominal obesity group regardless of
      sex. Abdominal obesity significantly increased the odds ratio (OR) for each
      adiponectin isoform level less than or equal to the median value in boys; the OR
      (95% confidence interval [CI]) was 2.50 (1.59-3.92) for high molecular weight
      adiponectin (HMW-adn), 2.47 (1.57-3.88) for medium molecular weight adiponectin
      (MMW-adn), and 1.75 (1.13-2.70) for low molecular weight adiponectin (LMW-adn).
      In girls, the OR (95% CI) was 1.95 (1.18-3.21) for HMW-adn, 1.40 (0.86-2.28) for
      MMW-adn, and 1.06 (0.65-1.70) for LMW-adn. CONCLUSIONS: Abdominal obesity was
      associated with lower adiponectin complexes and the influence of abdominal
      obesity varied by adiponectin isoform. Furthermore, the impact of abdominal
      obesity was larger in boys than in girls. The present study results suggest that
      prevention of abdominal obesity could contribute to the prevention of lower
      adiponectin levels, especially in boys.

PMID- 24670109
TI  - Enzyme-degradable self-assembled nanostructures from polymer-peptide hybrids.
AB  - The peptide PVGLIG, which is known to be selectively cleaved by the tumor
      associated enzyme matrix metalloproteinase-2 (MMP-2), was conjugated to alpha
      alkene poly(trimethylene carbonate) (PTMC) blocks of varying sizes via UV
      initiated thiol-ene "click" chemistry. The PTMC precursor was synthesized by
      metal-free ring-opening polymerization using allyl alcohol as an initiator and an
      N-heterocyclic carbene as an organic catalyst. The unprecedented PVGLIG-b-PTMC
      hybrids were self-assembled in aqueous solution and various submicrometer-sized
      morphologies obtained by a nanoprecipitation process. Characterization of
      particle morphology was carried out by multiangle dynamic light scattering (DLS)
      and static light scattering (SLS) evidencing spherical nanoparticles with
      different morphologies and narrow size distributions. Microstructure details were
      also observed on transmission electron micrographs and were in good agreement
      with light scattering measurements showing the assembly of core-shell, large
      compound micelles, and vesicle morphologies, the particle morphology varying with
      the hydrophilic weight fractions (f) of the hybrids. These nanostructures
      displayed selective degradation in the presence of the cancer-associated enzyme
      MMP-2, as probed by the morphological change both by TEM and DLS. All these
      results demonstrated that PVGLIG-b-PTMC hybrids were suitable to target the tumor
      microenvironment. 

PMID- 24670110
TI  - Condom negotiation: findings and future directions.
AB  - The aim of this review was to summarize factors associated with condom
      negotiation among heterosexual men. Literature searches were conducted using
      multiple databases spanning several disciplines. Studies examining psychological,
      demographic, relational, communication, and environmental factors related to
      condom negotiation are described, and a three-dimensional framework of condom
      negotiation is proposed. This framework of condom negotiation may aid researchers
      in operationalizing this construct, organizing this literature, and facilitating
      measurement development. We used this three-dimensional framework to articulate
      the influence of gender, ethnicity, relationship type, partner characteristics,
      trauma history, post-traumatic stress, and alcohol use on condom negotiation.
      Areas for future research are outlined. More research is needed to understand how
      these factors interact to influence condom negotiation, as well as the
      interaction between gender and the identified factors. 

PMID- 24670112
TI  - A reagent-controlled SN2-glycosylation for the direct synthesis of beta-linked 2
      deoxy-sugars.
AB  - The efficient and stereoselective construction of glycosidic linkages remains one
      of the most formidable challenges in organic chemistry. This is especially true
      in cases such as beta-linked deoxy-sugars, where the outcome of the reaction
      cannot be controlled using the stereochemical information intrinsic to the
      glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy
      sugar hemiacetals in situ as electrophilic species, which react stereoselectively
      with nucleophilic acceptors to produce beta-anomers exclusively. NMR studies
      confirm that, under these conditions, the hemiacetal is quantitatively converted
      into an alpha-glycosyl tosylate, which is presumably the reactive species in the
      reaction. This approach demonstrates that use of promoters that activate
      hemiacetals as well-defined intermediates can be used to permit stereoselective
      glycosylation through an SN2-pathway. 

PMID- 24670113
TI  - Stability of bicelles: a simulation study.
AB  - Aqueous mixtures of long-tailed lipids (e.g., dimyristoylphosphatidylcholine -
      DMPC) and detergents can sometimes form membrane disks called bicelles. Bicelles
      have found applications as an embedding medium for membrane proteins in the
      context of NMR studies and protein crystallization. However, the parameters that
      determine the thermodynamic stability of bicelles are not well understood. Here
      we report a coarse-grained simulation study of the relationship between lipid
      aggregate morphology and the composition and temperature of the surfactant
      mixture. In agreement with experiments, we find that bicellar mixtures are
      destabilized at higher temperatures and detergents are present at membrane edges
      as well as in flat membranes with a strong preference for the edges. In addition,
      our results suggest that the free-energy difference between bicelles and the
      perforated lamellar phase is typically very small for molecules without intrinsic
      curvature and charge. Cone shaped surfactant molecules tend to favor the
      formation of bicelles; however, none of the systems that we have studied provide
      unambiguous evidence for the existence of thermodynamically stable bicelles in
      mixtures of uncharged lipids with long and short tails. We speculate that small
      changes in the properties of the system (charge, dopants) may make bicelles
      thermodynamically stable. 

PMID- 24670111
TI  - Phenotypic characterisation of Saccharomyces spp. yeast for tolerance to stresses
      encountered during fermentation of lignocellulosic residues to produce
      bioethanol.
AB  - BACKGROUND: During industrial fermentation of lignocellulose residues to produce
      bioethanol, microorganisms are exposed to a number of factors that influence
      productivity. These include inhibitory compounds produced by the pre-treatment
      processes required to release constituent carbohydrates from biomass feed-stocks
      and during fermentation, exposure of the organisms to stressful conditions. In
      addition, for lignocellulosic bioethanol production, conversion of both pentose
      and hexose sugars is a pre-requisite for fermentative organisms for efficient and
      complete conversion. All these factors are important to maximise industrial
      efficiency, productivity and profit margins in order to make second-generation
      bioethanol an economically viable alternative to fossil fuels for future
      transport needs. RESULTS: The aim of the current study was to assess
      Saccharomyces yeasts for their capacity to tolerate osmotic, temperature and
      ethanol stresses and inhibitors that might typically be released during steam
      explosion of wheat straw. Phenotypic microarray analysis was used to measure
      tolerance as a function of growth and metabolic activity. Saccharomyces strains
      analysed in this study displayed natural variation to each stress condition
      common in bioethanol fermentations. In addition, many strains displayed tolerance
      to more than one stress, such as inhibitor tolerance combined with fermentation
      stresses. CONCLUSIONS: Our results suggest that this study could identify a
      potential candidate strain or strains for efficient second generation bioethanol
      production. Knowledge of the Saccharomyces spp. strains grown in these conditions
      will aid the development of breeding programmes in order to generate more
      efficient strains for industrial fermentations.

PMID- 24670114
TI  - Gene silencing of beta-galactosamide alpha-2,6-sialyltransferase 1 inhibits human
      influenza virus infection of airway epithelial cells.
AB  - BACKGROUND: Human influenza virus hemagglutinin prefers to use sialic acid (SA)
      receptors via alpha-2,6 linkages. The beta-galactoside alpha-2,6
      sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is
      responsible for the addition of alpha-2,6 linked SA to the Galbeta1-4GlcNAc
      disaccharide of glycans and glycoproteins found on the cellular surface.
      Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics.
      We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1
      and limit distribution of SA receptors on the surface of airway epithelial cells.
      RESULTS: The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and
      subsequent expression of the encoding protein. As a result, synthesis of alpha
      2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the
      surface of cells transfected with appropriate specific siRNAs was significantly
      reduced. Intracellular viral genome copy number and virus titer within the
      supernatant of cells transfected with siRNAs was significantly reduced in a dose
      dependent manner compared with those for untransfected cells and cells
      transfected with non-specific siRNAs. CONCLUSIONS: We used siRNAs targeting
      ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby
      preventing virus adsorption. This resulted in the inhibition of human influenza
      virus infection. Our findings are a significant development in the identification
      of potential new anti-influenza drug targets.

PMID- 24670115
TI  - Real time observation of the formation of hollow nanostructures through solid
      state reactions.
AB  - We demonstrate the formation of hollow nickel germanide nanostructures of Ni-Ge
      core-shell nanoparticles by solid state reactions. The structural evolutions of
      nickel germanide hollow nanostructures have been investigated in real-time
      ultrahigh vacuum transmission electron microscopy (UHV-TEM). Annealed above 450 
      degrees C, the nonequilibrium interdiffusion of core and shell species occurred
      at the interface; thus, Ni germanide hollow nanostructures were formed by solid
      state reactions involving the Kirkendall effect. In addition, the different
      hollow nanostructures formed from different core diameters of Ni-Ge core-shell
      nanoparticles have been studied. Also, we propose the mechanism with effects of
      the size and annealing duration on the solid state reactions based on the
      Kirkendall effect. 

PMID- 24670116
TI  - Effect of epicatechin gallate dietary supplementation on transgenic Drosophila
      model of Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by progressive loss of dopaminergic
      neurons and aggregation of alpha synuclein (alphaS) in the brain. The role of
      epicatechin gallate (EG) was studied on the transgenic Drosophila model of flies
      expressing normal human alpha synuclein (h-alphaS) in the neurons. The objectives
      of the present work include the study of the effect of EG on the climbing
      ability, lipid peroxidation, and apoptosis in the brain of PD model flies. These
      flies exhibit locomotor dysfunction as the age progresses. EG at final
      concentration of 0.25, 0.50, and 1.0 MUg/mL was supplemented in diet and flies
      were allowed to feed for 24 days. The climbing ability was assessed after 24
      days. The supplementation of 0.25, 0.50, and 1.0 MUg/mL of EG showed a dose
      dependent significant delay in the loss of climbing ability and reduced the
      oxidative stress and apoptosis in the brain of PD model flies.

PMID- 24670117
TI  - Quality characteristics and lutein bioavailability from maize and vegetable-based
      health food.
AB  - Health food (ready-mix) was prepared from maize and vegetables a source of lutein
      (L) and zeaxanthin (Z) and studied for its quality characteristics (moisture
      sorption isotherm, sensory, microbiological, chemical composition, and storage
      stability) on storage at varying temperatures for 3 months and L+Z
      bioavailability in mice. Results revealed a decrease in the L+Z level (4.70,
      9.24, and 13.85%) of ready-mix stored at 4, 27, and 37 degrees C, respectively.
      Critical relative humidity and critical moisture content of the product was 64%
      and 12.24%, respectively. The product is well accepted and was not affected
      adversely during storage. L+Z bioavailability from ready-mix in mice was higher
      in plasma (29.4%), liver (58.7%), and eye (14.6%) than control (mice received
      diet with purified L). To conclude, L+Z in the ready-mix is stable and more
      bioavailable than control. These findings may help in understanding the
      importance of simple food processing to improve L bioavailability under its
      deficient condition among an elderly population.

PMID- 24670118
TI  - Differential effects of 1,25-dihydroxyvitamin D3 on oral squamous cell carcinomas
      in vitro.
AB  - OBJECTIVE: The inverse association between vitamin D and cancer risk is well
      established, but the relationship with oral cancer is less well-understood. To
      further the understanding of these relationships, this study sought to evaluate
      any growth-inhibiting effects of vitamin D on well-characterized oral cancers.
      METHODS: This study utilized 1,25-dihydroxy Vitamin D3 to evaluate any changes in
      growth using CAL27, SCC15, and SCC25 oral cancer cell lines at physiological and
      supraphysiological concentrations. RESULTS: These assays revealed that the growth
      of all three cancer cell lines was significantly reduced by vitamin D
      administration, with maximal inhibition in SCC15 of -6.8% at 50 nmol, -19.7% in
      CAL27, and -43.6% in SCC25 at 100 nmol (p < .05). In addition, the observed
      decreases in growth were associated with significant decreases in viability
      (ranging from -18% in SCC15, -23% in CAL27, and -47% in SCC25 cells), as well as
      activation of two key apoptotic pathways (caspase and bcl:bax). CONCLUSION: The
      results of this study demonstrate the growth-inhibitory effects of vitamin D
      administration in specific oral cancer cell lines, which will enhance the
      understanding of oral oncologists and oral health researchers in developing
      standards for generalizing the health-protective effects of diet and dietary
      supplements as treatment options for patients with oral cancer.

PMID- 24670120
TI  - Timing influence of carbohydrate-protein ingestion on muscle soreness and next
      day running performance.
AB  - The present study investigates timing effects of a carbohydrate-protein (CHO
      PROT) beverage on indicators of muscle damage and next day running performance.
      Nine trained subjects completed three trials of a 30 min downhill run, followed
      by a 1.5 mile treadmill running time trial 24 hr later in a blinded, crossover
      design. Either a CHO-PROT or noncaloric placebo beverage was given 30 and 5 min
      prior to, at the 15 min mark during, immediately after, and 30 min after the
      downhill running protocol. In the first treatment (T1), a total of 360
      kilocalories were given 30 and 5 min prior to downhill running, as well as at the
      15 min mark, with placebos used at other time points. In the second treatment
      (T2), an isocaloric amount was given but only immediately after and 30 min after
      downhill running, with placebos used at other time points. In the placebo
      treatment, a placebo was given at all time points. There were no significant
      differences in the 1.5 mile time trial or soreness between trials (p > .05).
      Regardless of timing, the ingestion of a CHO-PROT beverage had no effect on next
      day running performance or muscular soreness versus a placebo.

PMID- 24670119
TI  - Greek pregnant women demonstrate inadequate micronutrient intake despite
      supplement use.
AB  - BACKGROUND/AIM: Maternal diet is important in the outcome of pregnancy and the
      health of the children. The present cross-sectional study aimed to assess the use
      of dietary supplements during pregnancy and define the maternal characteristics
      associated with supplement use. METHODS: The diet of 100 childbearing women was
      recorded for three consecutive days and micronutrient supplementation was added
      to the dietary intake and the median values were used in the analyses. RESULTS:
      The majority of the participants (92%) consumed at least one supplement.
      Supplementation of folic acid (FA) was significantly lower during the third
      trimester compared to the second (p <= .007). Higher intake of Ca and Fe
      supplements was observed in the second trimester (p <= .001). The use of
      supplements contributed to an attenuated consumption of all reported
      micronutrients (Mg, Ca, FA, and Fe, p <= .001). The principal components analysis
      revealed that the most important factor contributing to supplementation was
      primiparity. CONCLUSIONS: Overall, a high prevalence of micronutrient
      supplementation during pregnancy was observed without ensuring adequacy in the
      micronutrient intake. The increased rates of supplement users might be the result
      of an act for balancing diet in unplanned pregnancies.

PMID- 24670121
TI  - Determination of antioxidant capacity, alpha-amylase and lipase inhibitory
      activity of Crotalaria juncea Linn in vitro inhibitory activity of Crotalaria
      Juncea Linn.
AB  - The present study involves the determination of antioxidant capacity and in vitro
      alpha-amylase and lipase inhibitory activity of the Crotalaria juncea Linn
      extract. The content of polyphenols, flavonoids, and tannins in the extracts was
      estimated by spectrophotometry. Antioxidant activity on goat liver lipid
      peroxidation and linoleic acid emulsion were determined and alpha-amylase and
      lipase inhibitory activity was also evaluated. All the extracts had shown
      antioxidant property, alpha-amylase, and lipase inhibitory properties. Aqueous
      extract was found to show maximum antioxidant activity on goat liver. Antilipid
      peroxidation and antioxidant activity were determined to be 66.94 +/- 0.616 (p <
      .01) and 59.54 +/- 0.2 (p < .01), respectively. Maximum alpha-amylase and lipase
      inhibitory activities of 71.42 +/- 1.37 (p < .01) and 57.14 +/- 2.74% (p < .01),
      respectively, were exhibited by macerated methanol extract. The results had shown
      that all the extracts exhibited low inhibition and antioxidant activity as
      compared to standard.

PMID- 24670122
TI  - The effect of grape seed extract on estrogen levels of postmenopausal women: a
      pilot study.
AB  - The role of estrogens in breast cancer (BC) development is widely accepted,
      leading to the development of selective estrogen receptor modulators and
      aromatase inhibitors for BC treatment and prevention. However, because of
      potential adverse effects, healthy women with high risk of BC are hesitant to
      take them. Preliminary evidence from animal studies shows that grapes may have an
      aromatase-inhibiting effect, decreasing estrogen synthesis and increasing
      androgen precursors. We conducted a randomized, double-blind, dose-finding early
      phase trial on the effect of grape seed extract (GSE) on estrogen levels.
      Postmenopausal women who met study inclusion criteria (N = 46) were randomly
      assigned to daily GSE at a dose of 200, 400, 600, or 800 mg for 12 weeks. Primary
      outcome was change in plasma levels of estrogen conjugates from baseline to 12
      weeks posttreatment. Thirty-nine participants (84.8%) completed the study. GSE in
      the 4 daily doses did not significantly decrease estrogen or increase androgen
      precursors.

PMID- 24670123
TI  - An evidence-based systematic review of chlorophyll by the Natural Standard
      Research Collaboration.
AB  - An evidence-based systematic review of chlorophyll by the Natural Standard
      Research Collaboration consolidates the safety and efficacy data available in the
      scientific literature using a validated, reproducible grading rationale. This
      article includes written and statistical analysis of clinical trials, plus a
      compilation of expert opinion, folkloric precedent, history, pharmacology,
      kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

PMID- 24670124
TI  - Applying a correction procedure to the prevalence estimates of overweight and
      obesity in the German part of the HBSC study.
AB  - BACKGROUND: Prevalence rates for overweight and obesity based on self-reported
      height and weight are underestimated, whereas the prevalence rate for underweight
      is slightly overestimated. Therefore a correction is needed. Aim of this study is
      to apply correction procedures to the prevalence rates developed on basis of
      (self-reported and measured) data from the representative German National Health
      Interview and Examination Survey for Children and Adolescents (KiGGS) to (self
      reported) data from the German Health Behaviour in School Aged Children (HBSC)
      study to determine whether correction leads to higher prevalence estimates of
      overweight and obesity as well as lower prevalence rates for underweight.
      METHODS: BMI classifications based on self-reported and measured height and
      weight from a subsample of the KiGGS study (2,565 adolescents aged 11-15) were
      used to estimate two different correction formulas. The first and the second
      correction function are described. Furthermore, the both formulas were applied to
      the prevalence rates from the HBSC study (7,274 adolescents aged 11-15) which are
      based on self-reports collected via self-administered questionnaires. RESULTS:
      After applying the first correction function to self-reported data of the HBSC
      study, the prevalence rates of overweight and obesity increased from 5.5% to 7.8%
      (compared to 10.4% in the KiGGS study) and 2.7% to 3.8% (compared to 7.8% in the
      KiGGS study), respectively, whereas the corrected prevalence rates of underweight
      and severe underweight decreased from 8.0% to 6.7% (compared to 5.7% in the KiGGS
      study) and from 5.5% to 3.3% (compared to 2.4% in the KiGGS study), respectively.
      Application of the second correction function, which additionally considers body
      image, led to further slight corrections with an increase of the prevalence rates
      for overweight to 7.9% and for obese to 3.9%. CONCLUSION: Subjective BMI can be
      used to determine the prevalence of overweight and obesity among children and
      adolescents. Where there is evidence of bias, the prevalence estimates should be
      corrected using conditional probabilities that link measured and subjectively
      assessed BMI from a representative validation study. These corrections may be
      improved further by considering body image as an additional influential factor.

PMID- 24670125
TI  - Current knowledge and impressions of speech-language pathologists of the swallow
      of persons who are obese.
AB  - PURPOSE: The overall goal of this study was to provide insight on the topic of
      dysphagia in the obese population. More specifically, the purpose of this study
      was to obtain preliminary descriptive data on the knowledge and impressions of
      speech-language pathologists (SLPs) working in the field of dysphagia on the
      swallow of persons who are obese. METHODS: One hundred seventy-seven SLPs
      responded to a web-based survey that was posted on two popular listserves that
      serve the dysphagia community. RESULTS: Descriptive results showed that nearly
      all SLPs have assessed and treated patients who are obese for dysphagia, that
      there is little consensus as to how the obese swallow compares to the normal
      swallow, and that there is a consensus that dysphagia observed in the obese
      population is most likely related to other concomitant disorders. CONCLUSIONS:
      Results provide preliminary insight into the knowledge and impressions of SLPs
      working with dysphagia and highlight the need for future research to determine
      (1) if there is an increased incidence of dysphagia in the obese population, and
      (2) if obesity itself constitutes a risk factor for dysphagia or if any dysphagia
      observed in this population is related to other comorbidities.

PMID- 24670126
TI  - Life changed existentially: a qualitative study of experiences at 6-8 months
      after mild stroke.
AB  - PURPOSE: To explore experiences of mild-stroke survivors in the context of early
      supported discharge. The meanings patients attributed to activities and
      participation in the home recovery process were our main interest. METHODS: Eight
      participants (45-80 years) from a randomised controlled study were selected for
      this sub-study. This purposive sample had received rehabilitation in their homes
      in the post-stroke acute phase of recovery as part of the larger study. Extensive
      interview data were analysed using an interpretive strategy and systematic text
      condensation. Coping theory was included in later stages of analysis. FINDINGS:
      The mild-stroke survivors' stories revealed that life had changed profoundly.
      Differences and similarities in experienced changes were related to: self
      perceived health, the body, practical activities, taking part in society, and
      self-perception. The findings showed the ways in which life changed for mild
      stroke survivors, experienced challenges, and survivors' thoughts about the
      future. CONCLUSIONS: Mild-stroke rehabilitation should focus more strongly on
      basic concerns related to self-perceived health, self-perception, and body, since
      these dimensions seem to complicate daily activities and close relationships.
      Professionals should also be aware of patients who experience an uncertain
      situation and unresolved rehabilitation needs, which still can be present 6-8
      months after the stroke. IMPLICATIONS FOR REHABILITATION: When living with mild
      stroke, entrance to practical and social activities seemed founded on the
      patients' perception of the body and self as comprehensible or not. Comprehending
      their own changed body and sense of self seem to be a long-term process when
      living with mild stroke. It is suggested that long-term follow-up be incorporated
      in home rehabilitation service, also in the context of early supported discharge.
      This may contribute to help patient cope more optimally with activities and
      participation of importance to them.

PMID- 24670127
TI  - Visualization of angiogenesis during cancer development in the polyoma middle T
      breast cancer model: molecular imaging with (R)-[11C]PAQ.
AB  - BACKGROUND: Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial
      mediator of tumour angiogenesis. High expression levels of the receptor have been
      correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for
      stratifying patients for anti-angiogenic therapy could therefore be valuable for
      increasing treatment success rates. The aim of this study was to investigate the
      pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting
      positron emission tomography (PET) tracer (R)-[11C]PAQ. METHODS: (R)-[11C]PAQ was
      evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of
      metastatic breast cancer. Mice at different stages of disease progression were
      imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with
      [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were
      also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis
      specific biomarkers. Additional pharmacokinetic studies were performed in rat and
      mouse. RESULTS: A heterogeneous uptake of (R)-[11C]PAQ was observed in the
      tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas
      with high radioactivity uptake and areas with elevated levels of VEGFR2. In some
      animals, a high focal uptake was observed in the lungs. The lung uptake
      correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG
      PET. The pharmacokinetic studies revealed a limited metabolism and excretion
      during the 1-h scan and a distribution of radioactivity mainly to the liver,
      kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and
      parathyroid glands. CONCLUSION: The results indicate that (R)-[11C]PAQ is a
      promising imaging biomarker for visualization of angiogenesis, based on VEGFR2
      expression, in primary tumours and during metastasis development.

PMID- 24670128
TI  - Identification of clinical parameters associated with serum oxidative stress in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: Reactive oxygen species (ROS) are considered to be involved in the
      pathobiology of rheumatoid arthritis (RA); however, their association with
      disease activity has not been elucidated. In this study, we measured reactive
      oxygen metabolites (ROM) in patients with RA using a new Free Radical Analytical
      System and determined clinical parameters associated with ROM. METHODS: One
      hundred and fifty-two patients with RA and 80 patients with diabetes mellitus
      (DM) were included in this observational study. To measure ROM, the d-ROM test
      was performed on blood samples drawn from all subjects. The correlation between
      ROM and biomarkers, disease activity, doses of methotrexate (MTX), and
      prednisolone (PSL) were investigated. RESULTS: There were significant, positive
      correlations between ROM and CRP, matrix metalloproteinase 3 (MMP3), Disease
      Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease
      Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). Multiple
      regression analysis revealed that CRP and DAS28-ESR were correlated with ROM.
      CONCLUSIONS: The serum level of ROM was associated with CRP and DAS28-ESR,
      suggesting that ROM, in conjunction with CRP and MMP3, may be able to be used as
      a new biological disease marker to evaluate the disease activity of RA.

PMID- 24670129
TI  - Efficacy of anti-ribosomal P protein antibody testing for diagnosis of systemic
      lupus erythematosus.
AB  - OBJECTIVE: Anti-ribosomal P protein antibody (anti-P) is detected in a fraction
      of systemic lupus erythematosus (SLE) patients, especially with lupus psychosis,
      lupus nephritis, and lupus hepatitis. However, it has been unclear whether anti-P
      testing is specific for SLE. The current studies were designed to examine the
      efficacy of serum anti-P testing in diagnosis of SLE. METHOD: Multicenter
      retrospective study was performed with 102 SLE patients, 102 patients with non
      SLE rheumatic diseases, and 100 normal healthy subjects, who gave informed
      consents. The diagnosis of SLE was confirmed according to the 1982 ACR revised
      criteria. Serum IgG anti-P was determined by ELISA using the C-terminal 22 amino
      acids of ribosomal P protein conjugated to human serum albumin. The specificity
      and sensitivity of anti-P were compared with those of anti-DNA, anti-Sm, and anti
      cardiolipin (CL) antibodies. RESULTS: Serum anti-P was positive in 38 of 102 SLE
      patients (37.3%), in 4 of 102 patients with non-SLE rheumatic diseases (3.9%),
      and in none of 100 normal subjects. Receiver operating characteristic (ROC) curve
      analysis revealed that anti-P provided higher AUC (area under the curve) than
      anti-Sm or anti-CL. Consistently, the sensitivity of anti-P (37.3%) was superior
      to that of anti-Sm (27.5%) and anti-CL (24.5%), but inferior to that of anti-DNA
      (51.0%), whereas the specificity of anti-P (96.1%) was superior to that of anti
      CL (86.3%) and comparable to that of anti-DNA (96.1%) and anti-Sm (96.1%).
      CONCLUSION: These results indicate that serum anti-P testing might be an
      effective measure in diagnosing SLE, providing better diagnostic efficiency than
      anti-Sm and anti-CL.

PMID- 24670130
TI  - An evaluation of oxidative stress and antioxidant capacity in patients with
      myofascial pain syndrome.
AB  - OBJECTIVE: To evaluate total antioxidant capacity (TAC) and total oxidative
      stress (TOS) values in patients with myofascial pain syndrome (MPS). METHOD: The
      study comprised 38 patients diagnosed with MPS and 30 healthy volunteers. The
      age, body mass index (BMI) and pain scores (evaluation by visual analogue scales)
      of all the participants were recorded. The TAC, TOS and oxidative stress index
      (OSI) levels were compared between the MPS and control groups. RESULTS: There was
      no significant difference between the MPS and control groups in respect of
      demographic characteristics. The TAC levels were determined to be significantly
      lower and TOS levels and OSI values, significantly higher in the MPS patients
      than in the control group. CONCLUSION: The results of this study determined that
      the oxidant/antioxidant balance was impaired in MPS patients and thus MPS can be
      considered to be related to an increase in oxidative stress.

PMID- 24670131
TI  - Periodic fever, aphthous stomatitis, pharyngitis and cervical adenopathy syndrome
      is associated with activation of GM-CSF and burst-like expression of IL-8 in
      peripheral blood.
AB  - INTRODUCTION: Periodic fever, aphthous stomatitis, pharyngitis and cervical
      adenopathy (PFAPA) is an autoinflammatory syndrome characterized by periodic
      fever with aphthous stomatitis, cervical lymphadenopathy, myalgia, and abdominal
      pain. Peripheral blood concentrations of selected cytokines of PFAPA patients
      during and between febrile episodes were analyzed in a search for PFAPA-specific
      molecular signature. METHODS: 23 children with PFAPA (age 6.07 +/- 2.94 years,
      range 5-9 years) and three control children with severe oropharyngeal infections
      (age 6.2 +/- 7.95 years, range 1-17 years) participated in the study. Peripheral
      blood concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma,
      GM-CSF, TNF-alpha were measured using Luminex technology. RESULTS: PFAPA febrile
      episodes were characterized by detection of GM-CSF - 134.07 +/- 315.5 pg/mL;
      significant (P < 0.001), compared to baseline and controls, elevation of
      concentrations of IL-8 (3193.7 +/- 2508 pg/mL vs. 100.36 +/- 119. pg/mL vs. 2.04
      +/- 4.08 pg/mL, respectively), IL-6 (1355.38 +/- 2026.53 pg/mL vs. 28.8 +/- 44.2
      pg/mL and 27.13 +/- 26.42 pg/mL, respectively). IL-1beta was detected only in
      febrile and afebrile PFAPA patients (922.8 +/- 1639 pg/mL vs. 10.98 +/- 19.4
      pg/ml, P < 0.002, respectively), but not in controls. Peripheral blood
      concentration of TNFalpha did not differ significantly between study groups. IL
      2, IL-4, IL-5, and IL-10 were negligible in all study subjects. DISCUSSION: PFAPA
      febrile episodes are characterized by activation of GM-CSF and IL-8 with Th1
      skewing. We propose a molecular mechanism governing this phenomenon.

PMID- 24670132
TI  - Application of a new immunohistology scoring system (IH score): analysis of TNF
      alpha in synovium related to disease activity score in infliximab-treated
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: This study aimed to analyze the relationship between the expression
      of tumor necrosis factor alpha (TNF-alpha) or interleukin-6 (IL-6) in synovium
      and the disease activity score (DAS) 28 (C-reactive protein, CRP) in treatment of
      infliximab for rheumatoid arthritis (RA). METHODS: Synovial tissues were obtained
      from 16 infliximab-treated patients and assessed for TNF-alpha and IL-6 with a
      new immunohistology (IH) scoring system. The validation of IH score was performed
      and applied for the analysis of correlation between synovial TNF-alpha or IL-6
      and DAS28 (CRP) in addition to Rooney score. RESULTS: The IH score had high
      internal validity; the IH score of TNF-alpha strongly correlated with serum CRP
      and matrix metalloprotease-3 (MMP-3), as well as DAS28 (CRP) and the Rooney
      score. IL-6 did not correlate with DAS28 (CRP). CONCLUSIONS: This study indicates
      that the IH score is useful as a new procedure to assess the cytokine expression
      easily and TNF-alpha in synovium correlates with disease activity in patients
      with RA treated with infliximab.

PMID- 24670133
TI  - Current prevalence and characteristics of cervical spine instability in patients
      with rheumatoid arthritis in the era of biologics.
AB  - OBJECTIVES: Cervical spine instability (CSI) is commonly involved in patients
      with rheumatoid arthritis (RA). Although the treatment for RA has dramatically
      changed due to methotrexate and biologics, it is unclear whether this change
      contributes to the prevalence of CSI or not. Our objectives were to update the
      current prevalence of CSI and to investigate the factors associated with CSI.
      METHODS: A cross-sectional study of patients with RA was conducted in our
      outpatient clinic. Clinical information and symptoms related to CSI were
      obtained. Plain radiography and magnetic resonance imaging were performed. CSI
      included atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial
      subluxation (SAS). RESULTS: Two hundred and twenty patients were analyzed, 93
      (42%) of whom had CSI. A >= 10-year disease duration, Steinbrocker stage III, and
      three or more narrowed disc spaces from C2/3 to C6/7 were significantly
      associated with CSI. A neck pain VAS was associated with VS, but not with AAS and
      SAS. In contrast, methotrexate and biologics had no effect on CSI. CONCLUSION:
      The prevalence of CSI in this study was lower compared to previous reports before
      the approval of biologic, although we failed to detect the effect of biologics.
      Further prospective studies are needed to elucidate the efficacy.

PMID- 24670134
TI  - Comparison of radioimmunoprecipitation versus antigen-specific assays for
      identification of myositis-specific autoantibodies in dermatomyositis patients.
AB  - BACKGROUND: To confirm the antigen specificities of autoantibodies that
      precipitate 140-kDa (anti-p140) or 155/140-kDa polypeptides (anti-p155/140)
      previously identified by radioimmunoprecipitation in Korean patients with
      dermatomyositis (DM) and to look into the relationship between each MSA and
      clinical features of DM. METHODS: Seventeen serum samples of classic DM patients
      who had been found to have either anti-p140 antibodies (n = 9) or anti-p155/140
      (n = 8) antibodies in our previous study were examined using enzyme-linked
      immunosorbent assay (for anti-MDA5 antibodies) and immunoblotting (for anti
      MJ/NXP-2 and anti-TIF-1gamma antibodies). RESULTS: Seven out of nine anti-p140
      antibody positive patients were found to have anti-MDA5 antibodies. Two out of
      nine had anti-MJ/NXP-2 antibodies with no interstitial lung disease (ILD). All
      eight anti-p155/140 antibody positive patients were found to have anti-TIF-1gamma
      antibodies. Anti-TIF-1gamma and anti-MDA5 antibodies were simultaneously detected
      in one patient with anti-p155/140 antibody, who suffered HIV infection and non
      Hodgkin's lymphoma. The associations between anti-MDA5 antibody and rapidly
      progressive ILD and between anti-TIF-1gamma antibody and cancer-associated DM
      were confirmed to be significant. CONCLUSIONS: Although radioimmunoprecipitation
      still looks to be a good screening tool, confirmation with antigen-specific
      assays seems mandatory. The associations between anti-MDA5 and rapidly
      progressive ILD and between anti-TIF-1gamma and cancer-associated DM were
      confirmed in Korean patients with DM.

PMID- 24670135
TI  - Weighting with the Lansbury articular index improves the correlation of
      ultrasound score with serum matrix metalloproteinase-3 level in rheumatoid
      arthritis patients.
AB  - OBJECTIVE: To determine whether weighting improves the correlation of ultrasound
      (US) score with serum matrix metalloproteinase-3 (MMP-3) level in rheumatoid
      arthritis (RA). METHODS: As ultrasound examination was performed on 100 RA
      patients, and the severity of synovial effusion and synovial hypertrophy and the
      blood flow were semi-quantitatively graded from 0 to 3 by using the gray-scale
      (GS) and power Doppler (PD) modes. We then calculated the sums of the scores of
      the 28 joints of each patient in the 2 modes, that is, the GS28 and PD28 scores,
      as well as the respective scores weighted using the Lansbury articular index
      (LAI, shoulder and elbow, * 12; wrist, * 8; and knee, * 24)-Lans GS28 and Lans
      PD28 scores. RESULT: The Lans PD28 score showed a higher correlation with MMP-3
      (r = 0.591; 95% confidence interval, 0.446-0.705, p < 0.0001) than the existing
      measures. The scores of the large joints-the knee, shoulder, and elbow-correlated
      well with the serum MMP-3 level. CONCLUSION: Weighting with the LAI can improve
      the correlation of US findings with serum MMP-3 level. Bidirectional approach
      based on both serum MMP-3 level and US scores can further improve the assessment
      of disease activity in RA patients.

PMID- 24670136
TI  - The clinical characteristics of patients with IgG4-related disease with
      infiltration of the labial salivary gland by IgG4-positive cells.
AB  - OBJECTIVES: Mikulicz's disease (MD) is an immunoglobulin (Ig) G4-related disease
      with systemic symptoms. Submandibular gland (SMG) biopsy is recommended for
      patients with possible IgG4-related MD for accurate differential diagnosis;
      however, it is difficult for certain patients to undergo this procedure. In
      contrast, labial salivary gland (LSG) biopsy is more convenient. Here we present
      an analysis of patients with IgG4-related MD whose LSG specimens were infiltrated
      with abundant IgG4-positive plasma cells. METHODS: Sixteen patients diagnosed
      with IgG4-related MD underwent simultaneous SMG and LSG biopsies. We evaluated
      patients' serological and (18)F-fluoro-2-deoxyglucose-positron emission
      tomography/computed tomography ((18)F-FDG-PET/CT) and grouped them as LSG+ (LSG
      specimens with > 40% IgG4-positive plasma cells/IgG-positive plasma cells, 11
      patients) or LSG- (LSG specimens with < 40% IgG4-positive plasma cells/IgG
      positive plasma cells, 6 patients). RESULTS: There were not significant
      differences in serum IgG and IgG4 levels between the two groups; however, serum
      concentrations of soluble interleuikin-2 receptor (sIL-2R) were significantly
      higher in the LSG+ group. All patients with increased (18)F-FDG uptake in their
      parotid glands were a part of the LSG+ group. CONCLUSIONS: When a SMG biopsy is
      not possible, the serum concentration of sIL-2R and (18)F-FDG-PET/CT findings may
      predict whether LSG biopsy will facilitate the diagnosis of IgG4-related MD.

PMID- 24670137
TI  - Screening of Caatinga plants as sources of lectins and trypsin inhibitors.
AB  - Although it is one of the most threatened areas in the Earth, there are few
      studies on the biotechnological potential of the Caatinga. This work evaluated 36
      extracts from 27 Caatinga plants for lectin and trypsin inhibitor activities. The
      presence of lectin was detected in 77.7% of samples by haemagglutinating assay.
      The highest values of specific haemagglutinating activity were found in extracts
      of leaves from Mimosa lewesii, Bauhinia acuruana and Manilkara rufula and in
      branches from Myracrodruon urundeuva. Trypsin inhibitor activity was detected in
      63.9% of the tested extracts, strong inhibitory effect (>70%) being found in 11
      samples. This work demonstrates that Caatinga is a potential source of bioactive
      plant proteins that can be isolated and studied for several applications. The
      biochemical prospecting of Caatinga is essential for collection of bioactive
      principles so as to add conservation value to the region. 

PMID- 24670138
TI  - Time-dependent comparative evaluation of some important biomarkers of acute
      cyanide poisoning in rats: an aid in diagnosis.
AB  - OBJECTIVE: The study focuses on time-dependent comparative evaluation of various
      biomarkers of acute cyanide poisoning in rats. METHODS: Blood gas (analyzer),
      lactate, pyruvate, cyanide, thiocyanate (spectrophotometer) and 2-amino-2
      thiazoline-4-carboxylic acid (ATCA; gas chromatography-mass spectrometry) in
      plasma or urine, and various physiological parameters (polygraph) were measured.
      RESULTS: Cyanide poisoning was characterized by elevated lactate, cyanide,
      thiocyanate and ATCA concentrations in plasma up to 15 min, 4, 16 and 24 h,
      respectively, while high urinary thiocyanate and ATCA levels were measured
      between 4 and 24 h. CONCLUSION: ATCA concentration in plasma and urine was found
      to be more reliable indicator of cyanide poisoning.

PMID- 24670139
TI  - Synthesis, characterization, and reactivity of ruthenium hydride complexes of N
      centered triphosphine ligands.
AB  - The reactivity of the novel tridentate phosphine ligand N(CH2PCyp2)3 (N
      triphos(Cyp), 2; Cyp = cyclopentyl) with various ruthenium complexes was
      investigated and compared that of to the less sterically bulky and less electron
      donating phenyl derivative N(CH2PPh2)3 (N-triphos(Ph), 1). One of these complexes
      was subsequently investigated for reactivity toward levulinic acid, a potentially
      important biorenewable feedstock. Reaction of ligands 1 and 2 with the precursors
      [Ru(COD)(methylallyl)2] (COD = 1,5-cycloocatadiene) and [RuH2(PPh3)4] gave the
      tridentate coordination complexes [Ru(tmm){N(CH2PR2)3-kappa(3)P}] (R = Ph (3),
      Cyp (4); tmm = trimethylenemethane) and [RuH2(PPh3){N(CH2PR2)3-kappa(3)P}] (R =
      Ph (5), Cyp (6)), respectively. Ligands 1 and 2 displayed different reactivities
      with [Ru3(CO)12]. Ligand 1 gave the tridentate dicarbonyl complex
      [Ru(CO)2{N(CH2PPh2)3-kappa(3)P}] (7), while 2 gave the bidentate, tricarbonyl
      [Ru(CO)3{N(CH2PCyp2)3-kappa(2)P}] (8). This was attributed to the greater
      electron-donating characteristics of 2, requiring further stabilization on
      coordination to the electron-rich Ru(0) center by more CO ligands. Complex 7 was
      activated via oxidation using AgOTf and O2, giving the Ru(II) complexes
      [Ru(CO)2(OTf){N(CH2PPh2)3-kappa(3)P}](OTf) (9) and [Ru(CO3)(CO){N(CH2PPh2)3
      kappa(3)P}] (11), respectively. Hydrogenation of these complexes under hydrogen
      pressures of 3-15 bar gave the monohydride and dihydride complexes
      [RuH(CO)2{N(CH2PPh2)3-kappa(3)P}] (10) and [RuH2(CO){N(CH2PPh2)3-kappa(3)P}]
      (12), respectively. Complex 12 was found to be unreactive toward levulinic acid
      (LA) unless activated by reaction with NH4PF6 in acetonitrile, forming
      [RuH(CO)(MeCN){N(CH2PPh2)3-kappa(3)P}](PF6) (13), which reacted cleanly with LA
      to form [Ru(CO){N(CH2PPh2)3-kappa(3)P}{CH3CO(CH2)2CO2H-kappa(2)O}](PF6) (14).
      Complexes 3, 5, 7, 8, 11, and 12 were characterized by single-crystal X-ray
      crystallography. 

PMID- 24670141
TI  - Integrated thick-film nanostructures based on spinel ceramics.
AB  - Integrated temperature-humidity-sensitive thick-film structures based on spinel
      type semiconducting ceramics of different chemical compositions and magnesium
      aluminate ceramics were prepared and studied. It is shown that temperature
      sensitive thick-film structures possess good electrophysical characteristics in
      the region from 298 to 358 K. The change of electrical resistance in integrated
      thick-film structures is 1 order, but these elements are stable in time and can
      be successfully used for sensor applications. 

PMID- 24670140
TI  - Exploring mechanisms of fatigue during repeated exercise and the dose dependent
      effects of carbohydrate and protein ingestion: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Muscle glycogen has been well established as the primary metabolic
      energy substrate during physical exercise of moderate- to high-intensity and has
      accordingly been implicated as a limiting factor when such activity is sustained
      for a prolonged duration. However, the role of this substrate during repeated
      exercise after limited recovery is less clear, with ongoing debate regarding how
      recovery processes can best be supported via nutritional intervention. The aim of
      this project is to examine the causes of fatigue during repeated exercise bouts
      via manipulation of glycogen availability through nutritional intervention, thus
      simultaneously informing aspects of the optimal feeding strategy for recovery
      from prolonged exercise. METHODS/DESIGN: The project involves two phases with
      each involving two treatment arms administered in a repeated measures design. For
      each treatment, participants will be required to exercise to the point of
      volitional exhaustion on a motorised treadmill at 70% of previously determined
      maximal oxygen uptake, before a four hour recovery period in which participants
      will be prescribed solutions providing 1.2 grams of sucrose per kilogram of body
      mass per hour of recovery (g.kg-1.h-1) relative to either a lower rate of sucrose
      ingestion (that is, 0.3 g.kg-1. h-1; Phase I) or a moderate dose (that is, 0.8
      g.kg-1.h-1) rendered isocaloric via the addition of 0.4 g.kg-1.h-1 whey protein
      hydrolysate (Phase II); the latter administered in a double blind manner as part
      of a randomised and counterbalanced design. Muscle biopsies will be sampled at
      the beginning and end of recovery for determination of muscle glycogen
      resynthesis rates, with further biopsies taken following a second bout of
      exhaustive exercise to determine differences in substrate availability relative
      to the initial sample taken following the first exercise bout. DISCUSSION: Phase
      I will inform whether a dose-response relationship exists between carbohydrate
      ingestion rate and muscle glycogen availability and/or the subsequent capacity
      for physical exercise. Phase II will determine whether such effects are dependent
      on glycogen availability per se or energy intake, potentially via protein
      mediated mechanisms. TRIAL REGISTRATION: ISRCTN87937960.

PMID- 24670142
TI  - Beyond human-centred automation - concepts for human-machine interaction in multi
      layered networks.

PMID- 24670143
TI  - A framework to support human factors of automation in railway intelligent
      infrastructure.
AB  - Technological and organisational advances have increased the potential for remote
      access and proactive monitoring of the infrastructure in various domains and
      sectors - water and sewage, oil and gas and transport. Intelligent Infrastructure
      (II) is an architecture that potentially enables the generation of timely and
      relevant information about the state of any type of infrastructure asset,
      providing a basis for reliable decision-making. This paper reports an exploratory
      study to understand the concepts and human factors associated with II in the
      railway, largely drawing from structured interviews with key industry decision
      makers and attachment to pilot projects. Outputs from the study include a data
      processing framework defining the key human factors at different levels of the
      data structure within a railway II system and a system-level representation. The
      framework and other study findings will form a basis for human factors
      contributions to systems design elements such as information interfaces and role
      specifications. 

PMID- 24670144
TI  - Promoting resilience and wellbeing through an outdoor intervention designed for
      Aboriginal adolescents.
AB  - INTRODUCTION: Aboriginal people in Canada (First Nations, Inuit and Metis) have a
      lower health status compared to the Canadian population. There is a particular
      concern about the mental health and wellbeing of First Nations adolescents living
      on reserves. Interventions following principles of outdoor education and
      adventure therapy appear to be an appropriate fit for this population. These
      approaches have proven effective in non-Aboriginal populations, yet there is very
      little evidence on the efficacy of these types of program for Aboriginal
      adolescents. The primary purpose of this study was to evaluate the impact of an
      outdoor adventure leadership experience (OALE) on the resilience and wellbeing of
      First Nations adolescents from one reserve community. The secondary purposes were
      to explore whether this impact was sustainable, and whether there were any
      intervening factors that may have influenced the impact. METHODS: The
      collaborative research team used a mixed-method design to evaluate the 10-day
      OALE for adolescents from Wikwemikong Unceded Indian Reserve in northern Ontario,
      Canada. The main outcome assessed was resilience, measured by self-report, using
      the 14-Item Resilience Scale (RS-14). Several other exploratory measures assessed
      other aspects of health and well-being. The questionnaire package was
      administered at three different time periods: (T1) one day before the OALE; (T2)
      one month after the OALE; and (T3) one year after the OALE. The Mental Component
      Score (MCS) of the SF-12v2 was used to confirm any changes in resilience. Open
      ended questions were appended to the questionnaire at the 1-year point to
      identify any intervening factors that may have impacted any changes in resilience
      and wellbeing. The primary analysis compared mean RS-14 scores at T1 with those
      at T2. Responses to the open-ended questions were analyzed using content
      analysis. RESULTS: Over two summers (2009 and 2010), 73 youth 12-18 years of age
      from Wikwemikong participated in a standardized 10-day OALE program. This
      represented 15% of the on-reserve population of adolescents in this age range.
      Survey responses from 59 (80.8%) participants were available for analysis at T1,
      compared to 47 (64.4%) at T2 and 33 (45.2%) at T3. The mean RS-14 score was 73.65
      at baseline, and this improved 3.40 points (<i>p</i>=0.011) between T1 and T2.
      However, the resilience scores at T3 (1 year post-OALE) had a mean of 74.19,
      indicating a return back to pre-OALE levels. The mean MCS score at T1 was 48.23
      and it improved over the subsequent two time periods. Several intervening factors
      reported at T3 may have influenced the decrease in resilience scores from T2 to
      T3. These included changes in family living situation, death in the family, and
      other life stressors that occurred over the course of the year. CONCLUSIONS:
      Outcome scores from this study provide a unique glimpse into the self-reported
      health and wellbeing for adolescents within one First Nations community in
      Canada. The OALE program was beneficial in promoting resilience for adolescents
      in Wikwemikong over the short-term. Future studies are necessary to assess
      whether the OALE (or similar outdoor type interventions) are effective within
      other communities.

PMID- 24670145
TI  - Should pharmacologists care about alternative splicing? IUPHAR Review 4.
AB  - Alternative splicing of mRNAs occurs in the majority of human genes, and most
      differential splicing results in different protein isoforms with possibly
      different functional properties. However, there are many reported splicing
      variations that may be quite rare, and not all combinatorially possible variants
      of a given gene are expressed at significant levels. Genes of interest to
      pharmacologists are frequently expressed at such low levels that they are not
      adequately represented in genome-wide studies of transcription. In single-gene
      studies, data are commonly available on the relative abundance and functional
      significance of individual alternatively spliced exons, but there are rarely data
      that quantitate the relative abundance of full-length transcripts and define
      which combinations of exons are significant. A number of criteria for judging the
      significance of splice variants and suggestions for their nomenclature are
      discussed. 

PMID- 24670146
TI  - Unexpectedly high affinity of a novel histamine H(3) receptor antagonist,
      GSK239512, in vivo in human brain, determined using PET.
AB  - BACKGROUND AND PURPOSE: This study aimed to investigate the relationship between
      the plasma concentration (PK) of the novel histamine H3 receptor antagonist,
      GSK239512, and the brain occupancy of H(3) receptors (RO) in healthy human
      volunteers. EXPERIMENTAL APPROACH: PET scans were obtained after i.v.
      administration of the H(3) -specific radioligand [(11) C]GSK189254. Each subject
      was scanned before and after single oral doses of GSK239512, at 4 and 24 h after
      dose. PET data were analysed by compartmental analysis, and regional RO estimates
      were obtained by graphical analysis of changes in the total volumes of
      distribution of the radioligand, followed by a correction for occupancy by the
      high affinity radioligand. The PK/RO relationship was analysed by a population
      modelling approach, using the average PK of GSK239512 during each scan. KEY
      RESULTS: Following administration of GSK239512, there was a reduction in the
      brain uptake of [(11) C]GSK189254 in all regions, including cerebellum. RO at 4 h
      was higher than at 24 h, and the PK/RO model estimated a PK associated with 50%
      of RO of 0.0068 ng.mL(-1) . This corresponds to a free concentration of 4.50 *
      10(-12 ) M (pK = 11.3). CONCLUSIONS AND IMPLICATIONS: The affinity of GSK239512
      for brain H3 receptors in humans in vivo is much higher than that expected from
      studies in vitro, and higher than that observed in PET studies in pigs. The study
      illustrates the utility of carrying out PET studies in humans early in drug
      development, providing accurate quantification of GSK239512 RO in vivo as a
      function of time and dose.

PMID- 24670147
TI  - The ryanodine receptor agonist 4-chloro-3-ethylphenol blocks ORAI store-operated
      channels.
AB  - BACKGROUND: Depletion of the Ca(2+) store by ryanodine receptor (RyR) agonists
      induces store-operated Ca(2+) entry (SOCE). 4-Chloro-3-ethylphenol (4-CEP) and 4
      chloro-m-cresol (4-CmC) are RyR agonists commonly used as research tools and
      diagnostic reagents for malignant hyperthermia. Here, we investigated the effects
      of 4-CEP and its analogues on SOCE. EXPERIMENTAL APPROACH: SOCE and ORAI1-3
      currents were recorded by Ca(2+) imaging and whole-cell patch recordings in rat
      L6 myoblasts and in HEK293 cells overexpressing STIM1/ORAI1-3. KEY RESULTS: 4-CEP
      induced a significant release of Ca(2+) in rat L6 myoblasts, but inhibited SOCE.
      The inhibitory effect was concentration-dependent and more potent than its
      analogues 4-CmC and 4-chlorophenol (4-ClP). In the HEK293 T-REx cells
      overexpressing STIM1/ORAI1-3, 4-CEP inhibited the ORAI1, ORAI2 and ORAI3 currents
      evoked by thapsigargin. The 2-APB-induced ORAI3 current was also blocked by 4
      CEP. This inhibitory effect was reversible and independent of the Ca(2+) release.
      The two analogues, 4-CmC and 4-ClP, also inhibited the ORAI1-3 channels. Excised
      patch and intracellular application of 4-CEP demonstrated that the action site
      was located extracellularly. Moreover, 4-CEP evoked STIM1 translocation and
      subplasmalemmal clustering through its Ca(2+) store-depleting effect via the
      activation of RyR, but no effect on STIM1 redistribution was observed in cells co
      expressing STIM1/ORAI1-3. CONCLUSION AND IMPLICATIONS: 4-CEP not only acts as a
      RyR agonist to deplete the Ca(2+) store and trigger STIM1 subplasmalemmal
      translocation and clustering, but also directly inhibits ORAI1-3 channels. These
      findings demonstrate a novel pharmacological property for the chlorophenol
      derivatives that act as RyR agonists.

PMID- 24670148
TI  - TLR9 and MyD88 are crucial for the maturation and activation of dendritic cells
      by paromomycin-miltefosine combination therapy in visceral leishmaniasis.
AB  - BACKGROUND AND PURPOSE: The combination of paromomycin-miltefosine is a
      successful anti-leishmanial therapy in visceral leishmaniasis (VL). This
      encouraged us to study its effect on Toll-like receptor (TLR)-mediated
      immunomodulation of dendritic cells (DC), as DC maturation and activation is
      crucial for anti-leishmanial activity. EXPERIMENTAL APPROACH: In silico protein
      ligand interaction and biophysical characterization of TLR9-drug interaction was
      performed. Interaction assays of HEK293 cells with different concentrations of
      miltefosine and/or paromomycin were performed, and NF-kappaB promoter activity
      measured. The role of TLR9 and MyD88 in paromomycin/miltefosine-induced
      maturation and activation of DCs was evaluated through RNA interference
      techniques. The effect of drugs on DCs was measured in terms of counter
      regulatory production of IL-12 over IL-10, and characterized by chromatin
      immunoprecipitation assay at the molecular level. KEY RESULTS: Computational and
      biophysical studies revealed that paromomycin/miltefosine interact with TLR9.
      Both drugs, as a monotherapy/combination, induced TLR9-dependent NF-kappaB
      promoter activity through MyD88. Moreover, the drug combination induced
      TLR9/MyD88-dependent functional maturation of DCs, evident as an up-regulation of
      co-stimulatory markers, enhanced antigen presentation by increasing MHC II
      expression, and increased stimulation of naive T-cells to produce IFN-gamma. Both
      drugs, by modifying histone H3 at the promoter level, increased the release of IL
      12, but down-regulated IL-10 in a TLR9-dependent manner. CONCLUSIONS AND
      IMPLICATIONS: These results provide the first evidence that the combination of
      paromomycin-miltefosine critically modifies the maturation, activation and
      development of host DCs through a mechanism dependent on TLR9 and MyD88. This has
      implications for evaluating the success of other combination anti-leishmanial
      therapies that act by targeting host DCs.

PMID- 24670149
TI  - Hypotensive effects of ghrelin receptor agonists mediated through a novel
      receptor.
AB  - BACKGROUND AND PURPOSE: Some agonists of ghrelin receptors cause rapid decreases
      in BP. The mechanisms by which they cause hypotension and the pharmacology of the
      receptors are unknown. EXPERIMENTAL APPROACH: The effects of ligands of ghrelin
      receptors were investigated in rats in vivo, on isolated blood vessels and on
      cells transfected with the only molecularly defined ghrelin receptor, growth
      hormone secretagogue receptor 1a (GHSR1a). KEY RESULTS: Three agonists of GHSR1a
      receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP
      in the anaesthetized rat. The effect was not reduced by either of two GHSR1a
      antagonists, JMV2959 or YIL781, at doses that blocked effects on colorectal
      motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated
      ghrelin or the unacylated ghrelin receptor agonist, AZP531. The early hypotension
      preceded a decrease in sympathetic nerve activity. Early hypotension was not
      reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin
      also relaxed isolated segments of rat mesenteric artery, and, less potently,
      relaxed aorta segments. The vascular relaxation was not reduced by JMV2959 or
      YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected
      HEK293 cells at nanomolar concentrations. JMV2959 and YIL781 both antagonized
      effects in these cells, with their pA2 values at the GHSR1a receptor being 6.55
      and 7.84. CONCLUSIONS AND IMPLICATIONS: Our results indicate a novel vascular
      receptor or receptors whose activation by ulimorelin, capromorelin and CP464709
      lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not
      activated by ghrelin.

PMID- 24670150
TI  - The MCH(1) receptor, an anti-obesity target, is allosterically inhibited by 8
      methylquinoline derivatives possessing subnanomolar binding and long residence
      times.
AB  - BACKGROUND AND PURPOSE: Melanin-concentrating hormone receptor 1 (MCH1 receptor)
      antagonists are being considered as anti-obesity agents. The present study
      reports a new class of MCH1 receptor antagonists with an 8-methylquinoline
      scaffold. The molecular mechanism of MCH1 receptor blockade by these antagonists
      was examined. EXPERIMENTAL APPROACH: The pharmacological properties of the 8
      methylquinolines as exemplified by MQ1 were evaluated by use of multiple
      biophysical and cell-based functional assays. KEY RESULTS: Multiple signalling
      pathways for Galphai and Galphaq , and beta-arrestin were inhibited by MQ1.
      Furthermore, MQ1 produced an insurmountable antagonism, causing a rightward shift
      of the curve for concentration-dependent binding of MCH along with a progressive
      reduction of the maximal response. The dissociation kinetics for MQ1 were
      determined from washout experiments as well as by affinity selection-MS. In
      short, MQ1 was shown to be a slowly dissociating reversible MCH1 receptor blocker
      with a low Koff value. CONCLUSION AND IMPLICATIONS: This is the first time that a
      slowly dissociating negative allosteric modulator of the MCH1 receptor has been
      demonstrated to inhibit the numerous signalling pathways of this receptor. The
      characteristics of MQ1 are superior and distinct from previously reported MCH1
      receptor antagonists, making members of this chemotype attractive as drug
      candidates.

PMID- 24670152
TI  - Quantitative proteomics of extracellular vesicles released from human monocyte
      derived macrophages upon beta-glucan stimulation.
AB  - Fungal infections (mycoses) are common diseases of varying severity that cause
      problems, especially to immunologically compromised people. Fungi express a
      variety of pathogen-associated molecular patterns on their surface including beta
      glucans, which are important immunostimulatory components of fungal cell walls.
      During stimulatory conditions of infection and colonization, besides intensive
      intracellular response, human cells actively communicate on the intercellular
      level by secreting proteins and other biomolecules with several mechanisms.
      Vesicular secretion remains one of the most important paths for the proteins to
      exit the cell. Here, we have used high-throughput quantitative proteomics
      combined with bioinformatics to characterize and quantify vesicle-mediated
      protein release from beta-glucan-stimulated human macrophages differentiated in
      vitro from primary blood monocytes. We show that beta-glucan stimulation induces
      vesicle-mediated protein secretion. Proteomic study identified 540 distinct
      proteins from the vesicles, and the identified proteins show a proteomic
      signature characteristic for their cellular origin. Importantly, we identified
      several receptors, including cation-dependent mannose-6-phosphate receptor,
      macrophage scavenger receptor, and P2X7 receptor, that have not been identified
      from vesicles before. Proteomic data together with detailed pathway and network
      analysis showed that integrins and their cytoplasmic cargo proteins are highly
      abundant in extracellular vesicles released upon beta-glucan stimulation. In
      conclusion, the present data provides a solid basis for further studies on the
      functional role of vesicular protein secretion upon fungal infection. 

PMID- 24670153
TI  - Hidden potential of tropical fruit waste components as a useful source of remedy
      for obesity.
AB  - The array of comorbidities that comes with obesity and the propelling surge of
      this disease globally today make the urgent need for treatment vital. Although
      promoting a healthy physical regimen and controlled diet to affected patients are
      the main bulk of present treatment, prescriptions of weight-loss medications have
      also been introduced to complement this treatment. However, the use of synthetic
      medications may produce adverse side effects and consequently affect the
      patient's quality of life. In view of these problems, the use of natural sources
      as alternative remedies has recently become very popular. Tropical fruit "waste
      components", namely, the seed, flower, leaf, peel, and part of the fruit, which
      are often discarded after consumption, have recently been studied and showed
      evidence suggesting their potential as promising future alternative sources of
      remedy. The high amounts of phytochemicals present in these components were
      believed to be responsible for the antiobesity effect observed experimentally.
      This review aims to introduce some of the recently discussed tropical fruit waste
      components that have been discovered to possess antiobesity effects. The major
      bioactive compounds of the respective fruit components identified and deduced to
      be responsible for the overall bioactivity will be evaluated. Following this, the
      subsequent need for the development of an effective processing or recycling
      technique required to effectively tap the maximum potential of these fruit parts
      will also be addressed. 

PMID- 24670151
TI  - Information use and plasticity in the reproductive decisions of malaria
      parasites.
AB  - BACKGROUND: Investment in the production of transmissible stages (gametocytes)
      and their sex ratio are malaria parasite traits that underpin mosquito
      infectivity and are therefore central to epidemiology. Malaria parasites adjust
      their levels of investment into gametocytes and sex ratio in response to changes
      in the in-host environment (including red blood cell resource availability, host
      immune responses, competition from con-specific genotypes in mixed infections,
      and drug treatment). This plasticity appears to be adaptive (strategic) because
      parasites prioritize investment (in sexual versus asexual stages and male versus
      female stages) in manners predicted to maximize fitness. However, the
      information, or 'cues' that parasites use to detect environmental changes and
      make appropriate decisions about investment into gametocytes and their sex ratio
      are unknown. METHODS: Single genotype Plasmodium chabaudi infections were exposed
      to 'cue' treatments consisting of intact or lysed uninfected red blood cells,
      lysed parasitized RBCs of the same clone or an unrelated clone, and an
      unmanipulated control. Infection dynamics (proportion of reticulocytes, red blood
      cell and asexual stage parasite densities) were monitored, and changes in
      gametocyte investment and sex ratio in response to cue treatments, applied either
      pre- or post-peak of infection were examined. RESULTS AND CONCLUSIONS: A
      significant reduction in gametocyte density was observed in response to the
      presence of lysed parasite material and a borderline significant increase in sex
      ratio (proportion of male gametocytes) upon exposure to lysed red blood cells
      (both uninfected and infected) was observed. Furthermore, the changes in
      gametocyte density and sex ratio in response to these cues depend on the age of
      infection. Demonstrating that variation in gametocyte investment and sex ratio
      observed during infections are a result of parasite strategies (rather than the
      footprint of host physiology), provides a foundation to investigate the fitness
      consequences of plasticity and explore whether drugs could be developed to trick
      parasites into making suboptimal decisions.

PMID- 24670154
TI  - Comparison of serological and molecular panels for diagnosis of vector-borne
      diseases in dogs.
AB  - BACKGROUND: Canine vector-borne diseases (CVBD) are caused by a diverse array of
      pathogens with varying biological behaviors that result in a wide spectrum of
      clinical presentations and laboratory abnormalities. For many reasons, the
      diagnosis of canine vector-borne infectious diseases can be challenging for
      clinicians. The aim of the present study was to compare CVBD serological and
      molecular testing as the two most common methodologies used for screening healthy
      dogs or diagnosing sick dogs in which a vector-borne disease is suspected.
      METHODS: We used serological (Anaplasma species, Babesia canis, Bartonella
      henselae, Bartonella vinsonii subspecies berkhoffii, Borrelia burgdorferi,
      Ehrlichia canis, and SFG Rickettsia) and molecular assays to assess for exposure
      to, or infection with, 10 genera of organisms that cause CVBDs (Anaplasma,
      Babesia, Bartonella, Borrelia, Ehrlichia, Francisella, hemotropic Mycoplasma,
      Neorickettsia, Rickettsia, and Dirofilaria). Paired serum and EDTA blood samples
      from 30 clinically healthy dogs (Group I) and from 69 sick dogs suspected of
      having one or more canine vector-borne diseases (Groups II-IV), were tested in
      parallel to establish exposure to or infection with the specific CVBDs targeted
      in this study. RESULTS: Among all dogs tested (Groups I-IV), the molecular
      prevalences for individual CVBD pathogens ranged between 23.3 and 39.1%.
      Similarly, pathogen-specific seroprevalences ranged from 43.3% to 59.4% among
      healthy and sick dogs (Groups I-IV). Among these representative sample groupings,
      a panel combining serological and molecular assays run in parallel resulted in a
      4-58% increase in the recognition of exposure to or infection with CVBD.
      CONCLUSIONS: We conclude that serological and PCR assays should be used in
      parallel to maximize CVBD diagnosis.

PMID- 24670155
TI  - Ex situ reconstitution of the plant biopolyester suberin as a film.
AB  - Biopolymers often have unique properties of considerable interest as a basis for
      new materials. It is however not evident how to extract them from plants without
      destroying their chemical skeleton and inherent properties. Here we report the ex
      situ reconstitution of the biopolyester suberin as a new waterproof and
      antimicrobial material. In plant cell walls, suberin, a cross-linked network of
      aromatic and aliphatic monomers, builds up a hydrophobic protective and
      antimicrobial barrier. Recently we succeeded in extracting suberin from the plant
      cell wall using the ionic liquid cholinium hexanoate. During extraction the
      native three-dimensional structure of suberin was partially preserved. In this
      study, we demonstrate that this preservation is the key for its ex situ
      reconstitution. Without any chemical additives or purification, the suberin
      composing macromolecules undergo self-association on the casting surface forming
      a film. Suberin films obtained show barrier properties similar to those of the
      suberin barrier in plants, including a potentially broad bactericidal effect. 

PMID- 24670156
TI  - Miscalibrations in judgements of attractiveness with cosmetics.
AB  - Women use cosmetics to enhance their attractiveness. How successful they are in
      doing so remains unknown--how do men and women respond to cosmetics use in terms
      of attractiveness? There are a variety of miscalibrations where attractiveness is
      concerned--often, what one sex thinks the opposite sex finds attractive is
      incorrect. Here, we investigated observer perceptions about attractiveness and
      cosmetics, as well as their understanding of what others would find attractive.
      We used computer graphic techniques to allow observers to vary the amount of
      cosmetics applied to a series of female faces. We asked observers to optimize
      attractiveness for themselves, for what they thought women in general would
      prefer, and what they thought men in general would prefer. We found that men and
      women agree on the amount of cosmetics they find attractive, but overestimate the
      preferences of women and, when considering the preferences of men, overestimate
      even more. We also find that models' self-applied cosmetics are far in excess of
      individual preferences. These findings suggest that attractiveness perceptions
      with cosmetics are a form of pluralistic ignorance, whereby women tailor their
      cosmetics use to an inaccurate perception of others' preferences. These findings
      also highlight further miscalibrations of attractiveness ideals.

PMID- 24670158
TI  - Enantioselective synthesis and enhanced circularly polarized luminescence of S
      shaped double azahelicenes.
AB  - The enantioselective synthesis of azahelicenes and S-shaped double azahelicenes
      has been achieved via the Au-catalyzed sequential intramolecular hydroarylation
      of alkynes. The use of excess AgOTf toward a Au(I) complex is crucial for this
      transformation. Interestingly, the circularly polarized luminescence activity of
      the S-shaped double azahelicenes was significantly higher than that of the
      azahelicenes. 

PMID- 24670157
TI  - The Environment and Children's Health Care in Northwest China.
AB  - BACKGROUND: Industrialization in the northwest provinces of the People's Republic
      of China is accelerating rapid increases in early life environmental exposures,
      yet no publications have assessed health care provider capacity to manage common
      hazards. METHODS: To assess provider attitudes and beliefs regarding the
      environment in children's health, determine self-efficacy in managing concerns,
      and identify common approaches to managing patients with significant exposures or
      environmentally-mediated conditions, a two-page survey was administered to
      pediatricians, child care specialists, and nurses in five provinces (Gansu,
      Shaanxi, Xinjiang, Qinghai, and Ningxia). Descriptive and multivariable analyses
      assessed predictors of strong self-efficacy, beliefs or attitudes. RESULTS: 960
      surveys were completed with <5% refusal; 695 (72.3%) were valid for statistical
      analyses. The role of environment in health was rated highly (mean 4.35 on a 1-5
      scale). Self-efficacy reported with managing lead, pesticide, air pollution,
      mercury, mold and polychlorinated biphenyl exposures were generally modest (2.22
      2.52 mean). 95.4% reported patients affected with 11.9% reporting seeing >20
      affected patients. Only 12.0% reported specific training in environmental history
      taking, and 12.0% reported owning a text on children's environmental health.
      Geographic disparities were most prominent in multivariable analyses, with
      stronger beliefs in environmental causation yet lower self-efficacy in managing
      exposures in the northwestern-most province. CONCLUSIONS: Health care providers
      in Northwest China have strong beliefs regarding the role of environment in
      children's health, and frequently identify affected children. Few are trained in
      environmental history taking or rate self-efficacy highly in managing common
      hazards. Enhancing provider capacity has promise for improving children's health
      in the region.

PMID- 24670159
TI  - Fear and loathing in New England: examining the health-care perspectives of
      homeless people in rural areas.
AB  - Little anthropological research has been conducted on the health care
      perspectives of homeless people in rural areas. The aim of the present study is
      to elicit health-care beliefs, and examine overall health experience among a
      sample of current or recently homeless people in rural New Hampshire. Thirteen
      qualitative interviews were conducted, 11 with single men. Interviews were audio
      recorded and transcribed, and analyzed using thematic analysis. Despite a massive
      burden of disease and illness, almost all participants reported an abiding
      aversion to doctors, hospitals and professional health care. Participants
      reported numerous negative encounters with doctors and health care professionals,
      often of a demeaning and disparaging nature. Participants noted that these
      encounters resulted in frequent cases of misdiagnosis and iatrogenesis. In
      contrast, participants spoke more fondly of other social and voluntary services,
      for example homeless organizations. Like other rural New Englanders, participants
      made their own individual efforts to maintain and promote health, for example by
      pursuing hobbies or prayer. The findings are contextualized within literature
      suggesting that these perspectives are generally shared by other poor rural
      people. Consistent with this literature, the findings suggest that homelessness
      in rural areas is often temporary and episodic. As such, this paper brings into
      question the distinctiveness and overall utility of the concept: 'the rural
      homeless'. The key determinant of negative attitudes to health care may not be
      recent homelessness. It may be entrenched socio-economic marginalization, and the
      resultant social stigma, that are shared amongst the rural poor, regardless of
      their current housing status. 

PMID- 24670160
TI  - 'Islamic fatalism': life and suffering among Bangladeshi psychiatric patients and
      their families in London--an interview study 2.
AB  - An interview study of 44 Bangladeshi patients and relatives in eastern London
      demonstrated frequent appeals to God and deprecation of personal agency. This
      paper offers an interpretation of this apparent 'fatalism', which argues for the
      logical downplaying of human agency and ambition in archaic Arabia, contemporary
      rural Sylhet and among first generation Sylheti migrants in London. 

PMID- 24670161
TI  - Uncertainty, culture and pathways to care in paediatric functional
      gastrointestinal disorders.
AB  - This paper examines how children and families of diverse ethnic backgrounds
      perceive, understand and treat symptoms related to functional gastrointestinal
      disorders (FGIDs). It is questioned how different ways of dealing with medical
      uncertainty (symptoms, diagnosis) may influence treatment pathways. Semi
      structured interviews were conducted with 43 children of 38 family groups of
      immigrant and non-immigrant backgrounds. The analysis takes into account (a) the
      perceived symptoms; (b) the meaning attributed to them; and (c) the actions taken
      to relieve them. The social and cultural contexts that permeate these symptoms,
      meanings and actions were also examined. It is found that, in light of diagnostic
      and therapeutic uncertainty, non-immigrant families are more likely to consult
      health professionals. Immigrant families more readily rely upon home remedies,
      family support and, for some, religious beliefs to temper the uncertainty linked
      to abdominal pain. Furthermore, non-immigrant children lead a greater quest for
      legitimacy of their pain at home while most immigrant families place stomach
      aches in the range of normality. Intracultural variations nuance these findings,
      as well as family dynamics. It is concluded that different courses of action and
      family dynamics reveal that uncertainty is dealt with in multiple ways. Family
      support, the network, and trust in a child's expression of distress are key
      elements in order to tolerate uncertainty. Lastly, the medical encounter is
      described as a space permeated with relational uncertainty given the different
      registers of expression inherent within a cosmopolitan milieu. Narrative
      practices being an essential dynamic of this encounter, it is questioned whether
      families' voices are equally heard in these clinical spaces. 

PMID- 24670163
TI  - Pinching the poor? Medicaid cost sharing under the ACA.

PMID- 24670164
TI  - Diagnosing depression in older adults in primary care.

PMID- 24670165
TI  - Ceritinib in ALK-rearranged non-small-cell lung cancer.
AB  - BACKGROUND: Non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma
      kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but
      resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that
      has shown greater antitumor potency than crizotinib in preclinical studies.
      METHODS: In this phase 1 study, we administered oral ceritinib in doses of 50 to
      750 mg once daily to patients with advanced cancers harboring genetic alterations
      in ALK. In an expansion phase of the study, patients received the maximum
      tolerated dose. Patients were assessed to determine the safety, pharmacokinetic
      properties, and antitumor activity of ceritinib. Tumor biopsies were performed
      before ceritinib treatment to identify resistance mutations in ALK in a group of
      patients with NSCLC who had had disease progression during treatment with
      crizotinib. RESULTS: A total of 59 patients were enrolled in the dose-escalation
      phase. The maximum tolerated dose of ceritinib was 750 mg once daily; dose
      limiting toxic events included diarrhea, vomiting, dehydration, elevated
      aminotransferase levels, and hypophosphatemia. This phase was followed by an
      expansion phase, in which an additional 71 patients were treated, for a total of
      130 patients overall. Among 114 patients with NSCLC who received at least 400 mg
      of ceritinib per day, the overall response rate was 58% (95% confidence interval
      [CI], 48 to 67). Among 80 patients who had received crizotinib previously, the
      response rate was 56% (95% CI, 45 to 67). Responses were observed in patients
      with various resistance mutations in ALK and in patients without detectable
      mutations. Among patients with NSCLC who received at least 400 mg of ceritinib
      per day, the median progression-free survival was 7.0 months (95% CI, 5.6 to
      9.5). CONCLUSIONS: Ceritinib was highly active in patients with advanced, ALK
      rearranged NSCLC, including those who had had disease progression during
      crizotinib treatment, regardless of the presence of resistance mutations in ALK.
      (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number,
      NCT01283516.).

PMID- 24670167
TI  - Patches of disorganization in the neocortex of children with autism.
AB  - BACKGROUND: Autism involves early brain overgrowth and dysfunction, which is most
      strongly evident in the prefrontal cortex. As assessed on pathological analysis,
      an excess of neurons in the prefrontal cortex among children with autism signals
      a disturbance in prenatal development and may be concomitant with abnormal cell
      type and laminar development. METHODS: To systematically examine neocortical
      architecture during the early years after the onset of autism, we used RNA in
      situ hybridization with a panel of layer- and cell-type-specific molecular
      markers to phenotype cortical microstructure. We assayed markers for neurons and
      glia, along with genes that have been implicated in the risk of autism, in
      prefrontal, temporal, and occipital neocortical tissue from postmortem samples
      obtained from children with autism and unaffected children between the ages of 2
      and 15 years. RESULTS: We observed focal patches of abnormal laminar
      cytoarchitecture and cortical disorganization of neurons, but not glia, in
      prefrontal and temporal cortical tissue from 10 of 11 children with autism and
      from 1 of 11 unaffected children. We observed heterogeneity between cases with
      respect to cell types that were most abnormal in the patches and the layers that
      were most affected by the pathological features. No cortical layer was uniformly
      spared, with the clearest signs of abnormal expression in layers 4 and 5. Three
      dimensional reconstruction of layer markers confirmed the focal geometry and size
      of patches. CONCLUSIONS: In this small, explorative study, we found focal
      disruption of cortical laminar architecture in the cortexes of a majority of
      young children with autism. Our data support a probable dysregulation of layer
      formation and layer-specific neuronal differentiation at prenatal developmental
      stages. (Funded by the Simons Foundation and others.).

PMID- 24670166
TI  - Multistate point-prevalence survey of health care-associated infections.
AB  - BACKGROUND: Currently, no single U.S. surveillance system can provide estimates
      of the burden of all types of health care-associated infections across acute care
      patient populations. We conducted a prevalence survey in 10 geographically
      diverse states to determine the prevalence of health care-associated infections
      in acute care hospitals and generate updated estimates of the national burden of
      such infections. METHODS: We defined health care-associated infections with the
      use of National Healthcare Safety Network criteria. One-day surveys of randomly
      selected inpatients were performed in participating hospitals. Hospital personnel
      collected demographic and limited clinical data. Trained data collectors reviewed
      medical records retrospectively to identify health care-associated infections
      active at the time of the survey. Survey data and 2010 Nationwide Inpatient
      Sample data, stratified according to patient age and length of hospital stay,
      were used to estimate the total numbers of health care-associated infections and
      of inpatients with such infections in U.S. acute care hospitals in 2011. RESULTS:
      Surveys were conducted in 183 hospitals. Of 11,282 patients, 452 had 1 or more
      health care-associated infections (4.0%; 95% confidence interval, 3.7 to 4.4). Of
      504 such infections, the most common types were pneumonia (21.8%), surgical-site
      infections (21.8%), and gastrointestinal infections (17.1%). Clostridium
      difficile was the most commonly reported pathogen (causing 12.1% of health care
      associated infections). Device-associated infections (i.e., central-catheter
      associated bloodstream infection, catheter-associated urinary tract infection,
      and ventilator-associated pneumonia), which have traditionally been the focus of
      programs to prevent health care-associated infections, accounted for 25.6% of
      such infections. We estimated that there were 648,000 patients with 721,800
      health care-associated infections in U.S. acute care hospitals in 2011.
      CONCLUSIONS: Results of this multistate prevalence survey of health care
      associated infections indicate that public health surveillance and prevention
      activities should continue to address C. difficile infections. As device- and
      procedure-associated infections decrease, consideration should be given to
      expanding surveillance and prevention activities to include other health care
      associated infections.

PMID- 24670168
TI  - Mutant ZP1 in familial infertility.
AB  - The human zona pellucida is composed of four glycoproteins (ZP1, ZP2, ZP3, and
      ZP4) and has an important role in reproduction. Here we describe a form of
      infertility with an autosomal recessive mode of inheritance, characterized by
      abnormal eggs that lack a zona pellucida. We identified a homozygous frameshift
      mutation in ZP1 in six family members. In vitro studies showed that defective ZP1
      proteins and normal ZP3 proteins colocalized throughout the cells and were not
      expressed at the cell surface, suggesting that the aberrant ZP1 results in the
      sequestration of ZP3 in the cytoplasm, thereby preventing the formation of the
      zona pellucida around the oocyte. 

PMID- 24670169
TI  - Nutrition in the acute phase of critical illness.

PMID- 24670170
TI  - Images in clinical medicine. Neonatal thyrotoxicosis.

PMID- 24670171
TI  - Case records of the Massachusetts General Hospital. Case 10-2014. A 45-year-old
      man with a rash.

PMID- 24670172
TI  - Overcoming drug resistance in ALK-rearranged lung cancer.

PMID- 24670173
TI  - New FDA breakthrough-drug category--implications for patients.

PMID- 24670174
TI  - Arthroscopic partial meniscectomy for degenerative meniscal tear.

PMID- 24670175
TI  - Arthroscopic partial meniscectomy for degenerative meniscal tear.

PMID- 24670176
TI  - Arthroscopic partial meniscectomy for degenerative meniscal tear.

PMID- 24670177
TI  - Arthroscopic partial meniscectomy for degenerative meniscal tear.

PMID- 24670178
TI  - Abatacept in B7-1-positive proteinuric kidney disease.

PMID- 24670179
TI  - Abatacept in B7-1-positive proteinuric kidney disease.

PMID- 24670180
TI  - Abatacept in B7-1-positive proteinuric kidney disease.

PMID- 24670181
TI  - Endotracheal extubation.

PMID- 24670182
TI  - Endotracheal extubation.

PMID- 24670183
TI  - Endotracheal extubation.

PMID- 24670184
TI  - Endotracheal extubation.

PMID- 24670185
TI  - Ofatumumab for rituximab-resistant nephrotic syndrome.

PMID- 24670186
TI  - Thrombotic microangiopathy associated with interferon beta.

PMID- 24670188
TI  - Images in clinical medicine. Tonsillar asymmetry from a parotid tumor.

PMID- 24670189
TI  - De novo structure-based design of ion-pair triple-stranded helicates.
AB  - We present a generalized approach toward the design of ion-pair ML3A helicates
      assembled by coordination of metal cations (M) and anions (A) by ditopic
      chelating ligands (L). This computational approach, based on de novo structure
      based design principles implemented in the HostDesigner software, led to
      identification of synthetically accessible ditopic ligands that are structurally
      encoded to form charge-neutral ion-pair helicates with FeSO4 or LnPO4. 

PMID- 24670190
TI  - Exploring the experience of facilitating self-management with minority ethnic
      stroke survivors: a qualitative study of therapists' perceptions.
AB  - PURPOSE: The utility of self-management with people from minority ethnic
      backgrounds has been questioned, resulting in the development of culturally
      specific tools. Yet, the use of stroke specific self-management programmes is
      underexplored in these high risk groups. This article presents the experience of
      stroke therapists in using a stroke specific self-management programme with
      stroke survivors from minority ethnic backgrounds. METHODS: 26 stroke therapists
      with experience of using the self-management programme with stroke survivors from
      minority ethnic backgrounds participated in semi-structured interviews. These
      were audio recorded, transcribed verbatim and analysed thematically. RESULTS:
      Three themes were identified. One questioned perceived differences in stroke
      survivors interaction with self-management based on ethnicity. The other themes
      contrasted with this view demonstrating two areas in which ethnic and cultural
      attributes were deemed to influence the self-management process both positively
      and negatively. Aspects of knowledge of health, illness and recovery, religion,
      family and the professionals themselves are highlighted. CONCLUSIONS: This study
      indicates that ethnicity should not be considered a limitation to the use of an
      individualized stroke specific self-management programme. However, it highlights
      potential facilitators and barriers, many of which relate to the capacity of the
      professional to effectively navigate cultural and ethnic differences.

PMID- 24670191
TI  - "You plan, but you never know"--participation among people with different levels
      of severity of Parkinson's disease.
AB  - PURPOSE: The aim of this study was to improve our understanding of important
      aspects of participation in everyday life for people with different levels of
      severity of Parkinson's disease (PD). METHODS: A qualitative design was used,
      with empirical data obtained from focus groups. The participants had all been
      diagnosed with PD at least one year prior to the start of the study. Purposeful
      sampling was used to ensure that both sexes, with variations in age, marital
      status, living arrangements, education and employment, were represented.
      Recruitment continued until saturation was reached and resulted in 29
      participants. Homogeneity within each focus group was based on self-rated PD
      severity (mild, moderate or severe). FINDINGS: The aspects that influence
      participation at different stages of PD are that those with PD stand out in
      public, as a result of disease-specific features, and that the disease is
      unpredictable. Planning was highlighted as a strategy that is required to support
      participation and cope with stress and to compensate for the fact that everyday
      activities demanded a great deal of time and energy. CONCLUSION: These findings
      are of importance to the development of rehabilitation interventions that support
      people with PD in maintaining their participation in everyday life, throughout
      the course of the disease.

PMID- 24670192
TI  - The impact of STRENGTH on the expected and actual transition to home experience.
AB  - PURPOSE: The purpose of this study was to investigate the experiences and
      expectations of people with stroke, during their transition from hospital to
      home, after participating in a novel inpatient outreach program, entitled
      STRENGTH. METHODS: A qualitative study was conducted using semi-structured
      interviews, which were undertaken at discharge and 4-6 weeks post discharge.
      Thematic analysis was used to code the interview transcripts. RESULTS: The study
      incorporated data from seven people with stroke, who had a mean age of 61 years.
      Thematic analysis derived two themes, each with two sub-themes. The first theme
      was "Hospital and home" and described clients' experiences of therapy and the
      hospital environment. The second theme was "Life will never be what it was
      before" and elaborated on the adaptations and changing expectations that clients
      had before and after discharge. CONCLUSIONS: People with stroke described the
      therapy they received in both the hospital and home as beneficial. The results
      support the addition of the home-based inpatient program, STRENGTH, to the
      current rehabilitation system, as it appeared to realign the expectations of
      people with stroke and better prepare them for their discharge home.

PMID- 24670193
TI  - A step activity monitoring program improves real world walking activity post
      stroke.
AB  - PURPOSE: The purpose of this study was to examine whether the walking activity of
      persons with stroke could be increased through participation in a step activity
      monitoring program and to assess whether this occurred through a change in the
      structure of walking activity. METHOD: Sixteen individuals living with chronic
      stroke (>6 months post-stroke) wore a StepWatch Activity Monitor (SAM) and
      completed a four-week goal centered activity monitoring program. Descriptors of
      step activity were averaged across baseline and the last week of monitoring, and
      were used to analyze the changes. Descriptors of step activity included: steps
      per day, bouts per day, steps per bout, total time walking per day, and the
      number of short (<40 steps), medium (41-500 steps), and long (>500 steps) walking
      bouts. RESULTS: As a group, the number of steps per day significantly increased
      over the four weeks of activity monitoring (p = 0.005). Subjects also
      demonstrated a significant improvement in the total time walking (p = 0.023), and
      the number of medium (p = 0.033) and long (p = 0.050) walking bouts. At the
      baseline and the final assessment, more than half of the bouts were short bouts
      of walking (67.6 +/- 8% and 68.2 +/- 8% respectively). CONCLUSIONS: A goal
      centered step activity monitoring program can improve daily walking activity
      after stroke through increases in the amount of total time walking, and medium
      and long walking bouts.

PMID- 24670194
TI  - Isotachophoretic phenomena in electric field gradient focusing: perspectives for
      sample preparation and bioassays.
AB  - Isotachophoresis (ITP) and electric field gradient focusing (EFGF) are two
      powerful approaches for simultaneous focusing and separation of charged
      compounds. Remarkably, in many EFGF methods, isotachophoretic hallmarks have been
      found, including observations of plateau concentrations and contiguous analyte
      bands. We discuss the similarities between ITP and EFGF and describe promising
      possibilities to transfer the functionality and applications developed on one
      platform to other platforms. Of particular importance is the observation that
      single-electrolyte isotachophoretic separations with tunable ionic mobility
      window can be performed, as is illustrated with the example of depletion zone
      isotachophoresis (dzITP). By exploiting the rapid developments in micro- and
      nanofluidics, many interesting combinations of ITP and EFGF features can be
      achieved, yielding powerful analytical platforms for sample preparation,
      biomarker discovery, molecular interaction assays, drug screening, and clinical
      diagnostics. 

PMID- 24670195
TI  - Modeling swelling behavior of thermoresponsive polymer brush with lattice density
      functional theory.
AB  - A key problem in designing thermoresponsive polymer brushes on a solid surface is
      to find a relation between the targeted thermoresponsive properties and
      controllable conditions. Usually, a temperature-thickness curve showing the
      heating-induced swelling behavior of polymer brushes is chosen as the relation by
      either experimental or theoretical investigation. In this work, a lattice density
      functional theory (LDFT) developed previously is employed to investigate the
      temperature-thickness curves for five different types of polymer brushes, where
      the density profiles of polymer brushes calculated by LDFT are compared directly
      with simulation. It is found that the thermoresponsive behavior of a polymer
      brush can be characterized by the bulk phase behaviors of its corresponding
      polymer solution, including UCST, LCST, both UCST and LCST, closed LOOP and
      hourglass-shaped, which implies that the bulk phase diagram of polymer solutions
      can help us to find an appropriate polymer brush for a targeted thermoresponsive
      behavior. As an example, we show that the swelling behavior of a thermoresponsive
      polymer brush found in the experiment could be predicted by our LDFT results with
      the bulk phase diagram of real polymer solution only. 

PMID- 24670196
TI  - Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS):
      six-year results from a prospective, multicentre, non-interventional study in
      2,484 patients.
AB  - INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of
      rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in
      routine care, and to monitor changes in daily practice since the introduction of
      RTX therapy. METHODS: This was a multicentre, prospective, non-interventional
      study conducted under routine practice conditions in Germany. Efficacy was
      evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment
      Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse
      drug reactions (ADRs). Physician and patient global efficacy and tolerability
      assessments were also evaluated. RESULTS: Overall, 2,484 patients (76.7% female,
      mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment
      (22.7% monotherapy). The total observation period was approximately six-years
      (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and
      HAQ-DI that were sustained over multiple courses. DAS28 improvements positively
      correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and
      tolerability were rated good/very good by the majority of physicians and
      patients. Mean treatment intervals were 10.5 and 6.8 months for the first and
      last 400 enrolled patients, respectively. Infections were the most frequently
      reported ADRs (9.1%; 11.39/100 patient-years); approximately 1% of patients per
      course discontinued therapy due to ADRs. CONCLUSIONS: Prolonged RTX treatment in
      routine care is associated with good efficacy and tolerability, as measured by
      conventional parameters and by physicians' and patients' global assessments.
      Rheumatoid factor status served as a distinct and quantitative biomarker of RTX
      responsiveness. With growing experience, physicians repeated treatments earlier
      in patients with less severe disease activity.

PMID- 24670197
TI  - Nucleoside derivatives from the marine-derived fungus Aspergillus versicolor.
AB  - Four nucleoside derivatives (1-4) were isolated from the fungus Aspergillus
      versicolor derived from the gorgonian Dichotella gemmacea collected in the South
      China Sea. Their structures were elucidated by comprehensive spectroscopic method
      of NMR and MS analysis. All isolated metabolites were evaluated for their
      cytotoxicity, antibacterial activity and lethality towards brine shrimp Artemia
      salina. Compounds 1/2 exhibited selective antibacterial activity against
      Staphylococcus epidermidis with an MIC value of 12.5 MUM. It should be noted that
      1 and 2, whose structures were listed in SciFinder Scholar, had no associated
      reference. This is the first report about their isolation, structure elucidation
      and biological activities.

PMID- 24670198
TI  - Improved single molecule force spectroscopy using micromachined cantilevers.
AB  - Enhancing the short-term force precision of atomic force microscopy (AFM) while
      maintaining excellent long-term force stability would result in improved
      performance across multiple AFM modalities, including single molecule force
      spectroscopy (SMFS). SMFS is a powerful method to probe the nanometer-scale
      dynamics and energetics of biomolecules (DNA, RNA, and proteins). The folding and
      unfolding rates of such macromolecules are sensitive to sub-pN changes in force.
      Recently, we demonstrated sub-pN stability over a broad bandwidth (Deltaf = 0.01
      16 Hz) by removing the gold coating from a 100 MUm long cantilever. However, this
      stability came at the cost of increased short-term force noise, decreased
      temporal response, and poor sensitivity. Here, we avoided these compromises while
      retaining excellent force stability by modifying a short (L = 40 MUm) cantilever
      with a focused ion beam. Our process led to a ~10-fold reduction in both a
      cantilever's stiffness and its hydrodynamic drag near a surface. We also
      preserved the benefits of a highly reflective cantilever while mitigating gold
      coating induced long-term drift. As a result, we extended AFM's sub-pN bandwidth
      by a factor of ~50 to span five decades of bandwidth (Deltaf ~ 0.01-1000 Hz).
      Measurements of mechanically stretching individual proteins showed improved force
      precision coupled with state-of-the-art force stability and no significant loss
      in temporal resolution compared to the stiffer, unmodified cantilever. Finally,
      these cantilevers were robust and were reused for SFMS over multiple days. Hence,
      we expect these responsive, yet stable, cantilevers to broadly benefit diverse
      AFM-based studies. 

PMID- 24670199
TI  - The conserved upstream region of lscB/C determines expression of different
      levansucrase genes in plant pathogen Pseudomonas syringae.
AB  - BACKGROUND: Pseudomonas syringae pv. glycinea PG4180 is an opportunistic plant
      pathogen which causes bacterial blight of soybean plants. It produces the
      exopolysaccharide levan by the enzyme levansucrase. Levansucrase has three gene
      copies in PG4180, two of which, lscB and lscC, are expressed while the third,
      lscA, is cryptic. Previously, nucleotide sequence alignments of lscB/C variants
      in various P. syringae showed that a ~450-bp phage-associated promoter element
      (PAPE) including the first 48 nucleotides of the ORF is absent in lscA. RESULTS:
      Herein, we tested whether this upstream region is responsible for the expression
      of lscB/C and lscA. Initially, the transcriptional start site for lscB/C was
      determined. A fusion of the PAPE with the ORF of lscA (lscB(UpN)A) was generated
      and introduced to a levan-negative mutant of PG4180. Additionally, fusions
      comprising of the non-coding part of the upstream region of lscB with lscA
      (lscBUpA) or the upstream region of lscA with lscB (lscA(Up)B) were generated.
      Transformants harboring the lscB(UpN)A or the lscBUpA fusion, respectively,
      showed levan formation while the transformant carrying lscA(Up)B did not. qRT-PCR
      and Western blot analyses showed that lscB(UpN)A had an expression similar to
      lscB while lscB(Up)A had a lower expression. Accuracy of protein fusions was
      confirmed by MALDI-TOF peptide fingerprinting. CONCLUSIONS: Our data suggested
      that the upstream sequence of lscB is essential for expression of levansucrase
      while the N-terminus of LscB mediates an enhanced expression. In contrast, the
      upstream region of lscA does not lead to expression of lscB. We propose that lscA
      might be an ancestral levansucrase variant upstream of which the PAPE got
      inserted by potentially phage-mediated transposition events leading to expression
      of levansucrase in P. syringae.

PMID- 24670201
TI  - Normative influences on intentions to smoke among Greek adolescents: the
      moderating role of smoking status.
AB  - BACKGROUND: Social norms influence adolescent smoking intentions, but this effect
      may differentiate depending on current smoking experiences. The presented study
      assessed the moderation effects of smoking status on the relationship between
      social norms and smoking intentions among Greek adolescents. METHODS: A cross
      section survey-based design was used. Overall, 251 Greek secondary school
      students (M age = 16.1 years, 61.2% females) completed structured and anonymous
      questionnaires including demographic characteristics (age, gender), subjective
      and descriptive social norms towards smoking, self-reported tobacco use, and
      intentions to smoke in the next 12 months. RESULTS: Linear regression analysis
      showed that social norms overall predicted 36.4% (Adjusted R2) of the variance in
      intentions. Perceived prevalence of smoking in same age peers and adults, having
      more close friends who smoke and perceived social approval of smoking predicted
      intentions to smoke in one year. Moderated regression analysis showed that the
      effects of social norms on smoking intentions were significantly moderated by
      smoking status. CONCLUSIONS: Social norms predict smoking intentions, but this
      effect is stronger among ever (than never) smoker adolescents. Adolescents with
      smoking experiences may selectively attend to pro-smoking social cues and this
      perpetuates into their motivation to keep up the habit. School-based
      interventions should target normative beliefs and related cognitive processes,
      especially among adolescents who have already initiated tobacco use.

PMID- 24670200
TI  - The improving care in chronic obstructive lung disease study: CAROL improving
      processes of care and quality of life of COPD patients in primary care: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: The Swiss health ministry launched a national quality program
      'QualiCCare' in 2011 to improve health care for patients with COPD.The aim of
      this study is to determine whether participation in the COPD quality initiative
      ('QualiCCare') improves adherence to recommended clinical processes and shows
      impact on patients' COPD care and on the impact of COPD on a person's life.
      METHODS: CAROL is a cluster-randomized controlled trial with randomization on the
      general practioner (GP) level. Thirty GPs will be randomly assigned to equally
      sized intervention group or control group.Each GP will approach consecutively and
      regardless of the reason for the current consultation, patients aged 45 years or
      older, with a smoking history of >= ten pack-years (PY). Patients with confirmed
      (by spirometric evaluation) COPD will be included in the study. GPs in the
      intervention group will receive 'QualiCCare' education, which addresses
      knowledge, decision-making and behavioural aspects as well as delivery of care
      according to COPD quality indicators and evidence-based key elements. In the
      control group, no educational intervention will be applied and COPD patients will
      be treated as usual. The study period is one year.The primary outcome measure is
      an aggregated score of relevant clinical processes defining elements in the care
      of patients with COPD: smoking cessation counseling, influenza vaccination,
      motivation for physical activity, appropriate pharmacotherapy, patient education
      and collaborative care. Given a power of 90% and a significance level alpha of
      5%, 15 GPs recruiting eight patients each will be necessary in both study arms.
      With an assumed dropout rate of 20%, 288 patients will need to be included.
      DISCUSSION: It is important to develop and implement interventions that add value
      to COPD care considering quality and efficiency. Care pathways modifying the
      knowledge and behavior of physicians have the potential for improving care by
      transferring knowledge to clinical practice. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01921556.

PMID- 24670202
TI  - Implementation of an obstetric hemorrhage risk assessment: validation and
      evaluation of its impact on pretransfusion testing and hemorrhage outcomes.
AB  - OBJECTIVE: To evaluate the impact of an obstetric hemorrhage risk assessment on
      pretransfusion testing and hemorrhage outcomes at a tertiary care, academic
      medical center. METHODS: A retrospective cohort study was performed among women
      delivering neonates>=24 weeks from 2009 to 2011. Demographics, pretransfusion
      testing rates and hemorrhage outcomes were compared between those delivering
      before and after implementation of the risk assessment. Multivariable analyses
      were used to determine predictors of postpartum hemorrhage and transfusion.
      RESULTS: There were 1388 women delivering before and 2121 women delivering after
      implementation of the risk assessment. More pretransfusion testing occurred after
      the assessment was initiated (22.8% versus 15.0%). Those who were considered high
      risk were more likely to experience hemorrhage outcomes. In multivariable
      analyses, physician ordering practice in the pre-risk assessment period was a
      better prognosticator of both postpartum hemorrhage (aOR 9.98, 95% CI 5.02-19.82)
      and transfusion (aOR 31.14, 95% CI 14.97-64.82) than completion of a cross-match
      after implementation of the risk assessment (postpartum hemorrhage: aOR 2.10, 95%
      CI 1.20-3.66, transfusion: aOR 6.31, 95% CI 3.34-11.94). CONCLUSIONS: Pre-risk
      assessment practice may be better at identifying those in need of blood
      transfusion, strictly due to the necessity for pretransfusion orders for
      transfusion to occur. In contrast, the obstetric hemorrhage risk assessment
      accurately predicted those who were more likely to experience hemorrhage
      outcomes. Optimal utilization of the risk assessment has yet to be determined.

PMID- 24670203
TI  - Electrochemical access to 8-(1-phenyl-ethyl)-1,4-dioxa-8-aza-spiro[4.5]decane-7
      carbonitrile. Application to the asymmetric syntheses of (+)-myrtine and alkaloid
      (+)-241D.
AB  - The total syntheses of both enantiomers of trans-quinolizidine (+)-myrtine and
      cis-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our
      approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (
      )-11, which was prepared in four steps from alpha-amino nitrile 6 through a
      stereoselective alkylation-reduction decyanation process. alpha-Amino nitrile 6
      was prepared at the anode through electrochemical oxidation of 4-piperidone (+)
      5. In our study, alpha-phenylethylamine (alpha-PEA) allowed an efficient 1-3
      stereoinduction, and an orthogonal cleavage of the N-Boc protecting group in
      piperidone derivatives was carried out by stirring them in a suspension of
      SnCl4.(Et2O)2 complex in diethyl ether. When appropriate, the er's were
      determined by proton and carbon NMR spectroscopy utilizing (+)-tert
      butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents.

PMID- 24670204
TI  - Fabrication of epigallocatechin-3-gallate nanocarrier based on glycosylated
      casein: stability and interaction mechanism.
AB  - Polyphenols normally have strong binding affinity with proteins, which may lead
      to protein precipitation. Glycosylation of protein via Maillard reaction in mild
      condition may inhibit the precipitation. This study prepared nanocomplexes of
      epigallocatechin-3-gallate (EGCG) and protein, and their stability against
      environmental stress was investigated. Subsequently, these findings were
      correlated with the interactions between EGCG and casein. Results showed that
      glycosylated casein displayed strong encapsulating and retaining capacity to
      EGCG, and no obvious aggregation or fusion appeared in the concentration range of
      0.25-5.00 mg/mL during storage. The in vitro release demonstrated that casein,
      especially glycosylated casein, could effectively protect EGCG from degradation
      in alkaline pH and displayed a slow and sustained release in intestinal fluid,
      which may be attributed to the inhibiting effects of casein binding on the motion
      freedom of EGCG. Fluorescence quenching spectra demonstrated that the steric
      hindrance induced by dextran could inhibit the interaction between casein and
      EGCG. These findings demonstrated that glycosylated casein could be used as a
      promising and effective nanocarrier for EGCG. 

PMID- 24670205
TI  - Does the timing of treatment with intra-aortic balloon counterpulsation in
      cardiogenic shock due to ST-elevation myocardial infarction affect survival?
AB  - BACKGROUND: Intra-aortic balloon pump (IABP) counterpulsation and primary
      percutaneous coronary intervention (PCI) are standard treatment modalities in
      cardiogenic shock (CS) complicating acute myocardial infarction. The aim of this
      study was to investigate the impact of the timing of IABP treatment start in
      relation to PCI procedure. METHODS: Data were obtained from the SCAAR registry
      (Swedish Coronary Angiography and Angioplasty Registry) about 139 consecutive
      patients with CS due to ST-elevation myocardial infarction (STEMI) who received
      IABP treatment. The patients were hospitalized at Sahlgrenska University
      Hospital, Gothenburg, during 2004-2008. The cohort was divided into the two
      groups: group (A) in whom IABP treatment started before start of PCI (n = 72) and
      group (B) in whom IABP treatment started after PCI treatment (n = 67). The
      primary endpoint was 30-day mortality. Propensity score (PS) adjusted Cox
      proportional hazards regression was used to analyze predictors of 30-day
      mortality. RESULTS: Mean age was 66.5 +/- 12 and 28% were women. All patients
      have received IABP treatment 30 min before or 30 min after primary PCI. 63% had
      diabetes and 28% had hypertension. 16% were active tobacco smokers. The mortality
      rate at 30 days was 38%. IABP treatment commenced before or after PCI was not an
      independent predictor of mortality (P = 0.72). CONCLUSION: In this non-randomized
      trial the treatment with insertion of IABP before primary PCI in patients with CS
      due to STEMI is not associated with a more favorable outcome as compared with
      IABP started after primary PCI.

PMID- 24670207
TI  - "I remember thinking ...": Neural activity associated with subsequent memory for
      stimulus-evoked internal mentations.
AB  - Conscious thought involves an interpretive inner monologue pertaining to our
      waking experiences. Previous studies focused on the mechanisms that allow us to
      remember externally presented stimuli, but the neurobiological basis of the
      ability to remember one's internal mentations remains unknown. In order to
      investigate this question, we presented participants with sentences and scanned
      their neural activity using functional magnetic resonance imaging (fMRI) as they
      incidentally produced spontaneous internal mentations. After the scan, we
      presented the sentences again and asked participants to describe the specific
      thoughts they had during the initial presentation of each sentence. We
      categorized experimental trials for each participant according to whether they
      resulted in subsequently reported internal mentations or not. The results show
      that activation within classic language processing areas was associated with
      participants' ability to recollect their thoughts. Activation within mostly right
      lateralized and medial "default-mode network" regions was associated with not
      reporting such thoughts.

PMID- 24670206
TI  - Disruption of the nuclear p53-GAPDH complex protects against ischemia-induced
      neuronal damage.
AB  - Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is conventionally considered a
      critical enzyme that involves in glycolysis for energy production. Recent
      previous studies have suggested that GAPDH is important in glutamate-induced
      neuronal excitotoxicity, while accumulated evidence also demonstrated that GAPDH
      nuclear translocation plays a critical role in cell death. However, the molecular
      mechanisms underlying this process remain largely unknown. In this study, we
      showed that GAPDH translocates to the nucleus in a Siah1-dependent manner upon
      glutamate stimulation. The nuclear GAPDH forms a protein complex with p53 and
      enhances p53 expression and phosphorylation. Disruption of the GAPDH-p53
      interaction with an interfering peptide blocks glutamate-induced cell death and
      GAPDH-mediated up-regulation of p53 expression and phosphorylation. Furthermore,
      administration of the interfering peptide in vivo protects against ischemia
      induced cell death in rats subjected to tMCAo. Our data suggest that the nuclear
      p53-GAPDH complex is important in regulating glutamate-mediated neuronal death
      and could serve as a potential therapeutic target for ischemic stroke treatment. 

PMID- 24670208
TI  - A general and enantioselective approach to pentoses: a rapid synthesis of PSI
      6130, the nucleoside core of sofosbuvir.
AB  - An efficient route towards biologically relevant pentose derivatives is
      described. The de novo synthetic strategy features an enantioselective alpha
      oxidation reaction enabled by a chiral amine in conjunction with copper(II)
      catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of
      a wide array of modular two-carbon fragments. Lactone intermediates accessed via
      this route provide a useful platform for elaboration, as demonstrated by the
      preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this
      work has facilitated expedient syntheses of pharmaceutically active compounds
      currently in clinical use. 

PMID- 24670209
TI  - Biochemical and radical-scavenging properties of sea cucumber (Stichopus vastus)
      collagen hydrolysates.
AB  - The molecular mass distribution, amino acid composition and radical-scavenging
      activity of collagen hydrolysates prepared from collagen isolated from the sea
      cucumber Stichopus vastus were investigated. beta and alpha1 chains of the
      collagen were successfully hydrolysed by trypsin. The molecular mass distribution
      of the hydrolysates ranged from 5 to 25 kDa, and they were rich in glycine,
      alanine, glutamate, proline and hydroxyproline residues. The hydrolysates
      exhibited excellent radical-scavenging activity. These results indicate that
      collagen hydrolysates from S. vastus can be used as a functional ingredient in
      food and nutraceutical products.

PMID- 24670211
TI  - Making air quality indices comparable--assessment of 10 years of air pollutant
      levels in western Europe.
AB  - To address the incomparability of the large number of existing air quality
      indices, we propose a new normalization method that is suited to directly compare
      air quality indices based on the common European World Health Organization (WHO)
      air quality guidelines for NO2, O3, and PM10. Using this method, we compared
      three air quality indices based on the European guidelines, related them to
      another air quality index based on the relative risk concept, and used them to
      assess the air quality and its trends in northwest central Europe. The average
      air quality in the area of investigation is below the recommended European
      guidelines. The majority of index values exceeding this threshold are caused by
      PM10, which is also, in most cases, responsible for the degrading trends in air
      quality. Eleven out of 29 stations tested showed significant trends, of which
      eight indicated trends towards better air quality.

PMID- 24670210
TI  - Parasite densities modulate susceptibility of mice to cerebral malaria during co
      infection with Schistosoma japonicum and Plasmodium berghei.
AB  - BACKGROUND: Malaria and schistosomiasis are endemic and co-exist in the same
      geographic areas, even co-infecting the same host. Previous studies have reported
      that concomitant infection with Schistosoma japonicum could offer protection
      against experimental cerebral malaria (ECM) in mice. This study was performed to
      evaluate whether alterations in parasite density could alter this protective
      effect. METHODS: Mice were inoculated with 100 or 200 S. japonicum cercariae
      followed by infection with high or low density of Plasmodium berghei ANKA strain
      eight weeks after the first infection. Then, parasitaemia, survival rate and
      blood-brain-barrier (BBB) damage were assessed. Interferon-gamma (IFN-gamma),
      interleukin (IL)-4, IL-5, IL-13, IL-10, and TGF-beta levels were determined in
      splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). Cell
      surface/intracellular staining and flow cytometry were used to analyse the level
      of CD4(+)/CD8(+) T cells, CD4(+)CD25(+)Foxp3(+) Tregs, IL-10-secreting Tregs, and
      IL-10(+)Foxp3-CD4(+) T cells in the spleen, and CD4(+)/CD8(+) T cells
      infiltrating the brain. RESULTS: Co-infection with low density P. berghei and
      increased S. japonicum cercariae significantly increased the levels of IL-4, IL
      5, IL-13, TGF-beta and Tregs, but significantly decreased the levels of IFN-gamma
      and the percentage of CD4(+) T cells and CD8(+) T cells in the spleen and CD8(+)
      T cell infiltration in the brain. Increased worm loads also significantly
      decreased mortality and BBB impairment during ECM. When challenged with higher
      numbers of P. berghei and increased cercariae, the observed cytokine changes were
      not statistically significant. The corresponding ECM mortality and BBB impairment
      also remained unchanged. CONCLUSIONS: This study demonstrates that protection for
      ECM depends on the numbers of the parasites, S. japonicum and P. berghei, during
      co-infection. Alterations in the regulatory response appear to play a key role in
      this adaptation.

PMID- 24670212
TI  - Neurodevelopmental and environmental hypotheses of negative symptoms of
      schizophrenia.
AB  - The negative symptoms of schizophrenia, avolition, alogia, apathy and impaired or
      nonexistent social functioning, are strongly correlated with the progressive
      course and long-term prognosis of the disease, undermining the patient's ability
      to integrate socially, interpersonal skills and quality of life. At a time when
      new drug strategies are being developed, a better understanding of the etiology
      and pathogenesis underpinning the occurrence of negative symptoms constitutes an
      essential prerequisite for real therapeutic advances. Approaching this
      vulnerability from the neurodevelopmental perspective is especially pertinent
      with regard to the experimental studies conducted in animals. Several models have
      been put forward, involving a variety of topics such as the deleterious impact of
      a prenatal infection or of early maternal deprivation on brain development, or
      else the consequences of trauma and abuse suffered during childhood. These
      various models are based on biological abnormalities that could guide the
      identification of new therapeutic targets. They notably include the
      hyperreactivity of the hypothalamic-pituitary-adrenal axis and dysfunction of
      corticostriatal glutamatergic transmission. As such, in the traumagenic model,
      which associates neurodevelopmental and neurodegenerative processes, the
      dysfunction of corticostriatal glutamatergic transmission, by reducing the tonic
      dopamine release, could be the cause of an increase in the phasic dopamine
      release linked to stress. This excessive phasic response to stress may induce
      cerebral damage by increasing excitotoxicity and oxidative stress. 

PMID- 24670213
TI  - Cell wall composition of Bacillus subtilis changes as a function of pH and Zn2+
      exposure: insights from cryo-XPS measurements.
AB  - Bacteria play an important role in the biogeochemical cycling of metals in the
      environment. Consequently, there is an interest to understand how the bacterial
      surfaces interact with metals in solution and how this affects the bacterial
      surface. In this work we have used a surface-sensitive analysis technique,
      cryogenic X-ray photoelectron spectroscopy (cryo-XPS), to monitor the surface of
      Bacillus subtilis cells as a function of pH and Zn(2+) content in saline
      solution. The objective of the study was twofold: (1) to investigate the
      agreement between two data treatment methods for XPS, as well as investigate to
      what extent sample pretreatment may influence XPS data of bacterial samples, and
      (2) to characterize how the surface chemistry of bacterial cells is influenced by
      different external conditions. (1) It was found that the two data treatment
      methods gave rise to comparable results. However, identical samples analyzed fast
      frozen or dry exhibited larger differences in surface chemistry, indicating that
      sample pretreatment can to large extents influence the obtained surface
      composition of bacterial samples. (2) The bacterial cell wall (in fast-frozen
      samples) undergoes dramatic compositional changes with pH and with Zn(2+)
      exposure. The compositional changes are interpreted as an adaptive metal
      resistance response changing the biochemical composition of the bacterial cell
      wall. These results have implications for how adsorption processes at the surface
      of bacterial cells are analyzed, understood, modeled, and predicted. 

PMID- 24670215
TI  - Small interfering RNA directed against CTMP reduces acute traumatic brain injury
      in a mouse model by activating Akt.
AB  - OBJECTIVE: Protein kinase B (PKB/Akt), which is phosphorylated and activated by
      upstream activators, exerts critical neuroprotective effects by phosphorylating
      downstream targets after traumatic brain injury (TBI). Studies on the regulation
      of Akt will be crucial for our understanding of neuronal survival. The goal of
      this study is to investigate the effects of carboxyl-terminal modulator protein
      (CTMP) on phosphorylation of Akt and neurological function in a mouse model of
      TBI. METHODS: Traumatic brain injury in mice was performed by a controlled
      cortical impact device. The expression of Akt, phospho-Akt, and CTMP was examined
      in the injured cortices by immunohistochemistry and Western blot analysis. To
      determine the effects of CTMP, small interfering RNAs (siRNAs) directed against
      CTMP were injected in mice with TBI, and the expression of phosphorylated Akt and
      neurological function were evaluated. RESULTS: Phospho-Akt significantly
      increased at 4 hours post-TBI in the nucleus (P < 0.01) and remained at high
      levels until 72 hours after TBI, as shown by Western blot analysis. In the
      cytosol, the expression of phospho-Akt reached its peak at 4 hours post-TBI, but
      decreased markedly at 24 hours and maintained below pre-TBI levels until 72 hours
      post-TBI. Interestingly, the expression of CTMP significantly increased 4 hours
      after TBI (P < 0.01) and sustained those levels until 72 hours without dramatic
      changes. Treatment with CTMP siRNA effectively augmented the phosphorylation of
      Akt and significantly improved the neurological functional recovery up to 28 days
      post-TBI. CONCLUSION: We conclude that Akt is phosphorylated and translocated to
      nucleus after TBI to exert neuroprotective effects. However, CTMP is
      simultaneously triggered to inhibit the phosphorylation of Akt. Inhibition of
      CTMP by siRNA improves the recovery of neurological functions after TBI.

PMID- 24670216
TI  - Two-dimensional pattern formation using graphoepitaxy of PS-b-PMMA block
      copolymers for advanced FinFET device and circuit fabrication.
AB  - Directed self-assembly (DSA) of lamellar phase block-co-polymers (BCPs) can be
      used to form nanoscale line-space patterns. However, exploiting the potential of
      this process for circuit relevant patterning continues to be a major challenge.
      In this work, we propose a way to impart two-dimensional pattern information in
      graphoepitaxy-based lamellar phase DSA processes by utilizing the interactions of
      the BCP with the template pattern. The image formation mechanism is explained
      through the use of Monte Carlo simulations. Circuit patterns consisting of the
      active region of Si FinFET transistors, referred to as Si "fins", were fabricated
      to demonstrate the applicability of this technique to the formation of complex
      patterns. The quality of the Si fin features produced by this process was
      validated by demonstrating the first functional DSA-patterned FinFET devices with
      29 nm-pitch fins. 

PMID- 24670214
TI  - Colonizing while migrating: how do individual enteric neural crest cells behave?
AB  - BACKGROUND: Directed cell migration is essential for normal development. In most
      of the migratory cell populations that have been analyzed in detail to date, all
      of the cells migrate as a collective from one location to another. However, there
      are also migratory cell populations that must populate the areas through which
      they migrate, and thus some cells get left behind while others advance. Very
      little is known about how individual cells behave to achieve concomitant
      directional migration and population of the migratory route. We examined the
      behavior of enteric neural crest-derived cells (ENCCs), which must both advance
      caudally to reach the anal end and populate each gut region. RESULTS: The
      behavior of individual ENCCs was examined using live imaging and mice in which
      ENCCs express a photoconvertible protein. We show that individual ENCCs exhibit
      very variable directionalities and speed; as the migratory wavefront of ENCCs
      advances caudally, each gut region is populated primarily by some ENCCs migrating
      non-directionally. After populating each region, ENCCs remain migratory for at
      least 24 hours. Endothelin receptor type B (EDNRB) signaling is known to be
      essential for the normal advance of the ENCC population. We now show that
      perturbation of EDNRB principally affects individual ENCC speed rather than
      directionality. The trajectories of solitary ENCCs, which occur transiently at
      the wavefront, were consistent with an unbiased random walk and so cell-cell
      contact is essential for directional migration. ENCCs migrate in close
      association with neurites. We showed that although ENCCs often use neurites as
      substrates, ENCCs lead the way, neurites are not required for chain formation and
      neurite growth is more directional than the migration of ENCCs as a whole.
      CONCLUSIONS: Each gut region is initially populated by sub-populations of ENCCs
      migrating non-directionally, rather than stopping. This might provide a mechanism
      for ensuring a uniform density of ENCCs along the growing gut.

PMID- 24670217
TI  - A robust graft-to strategy to form multifunctional and stealth zwitterionic
      polymer-coated mesoporous silica nanoparticles.
AB  - Mesoporous silica nanoparticles (MSNs) are a new class of carrier materials
      promising for drug/gene delivery and many other important applications. Stealth
      coatings are necessary to maintain their stability in complex media. Herein, a
      biomimetic polymer conjugate containing one ultralow fouling poly(carboxybetaine)
      (pCBMA) chain and one surface-adhesive catechol (DOPA) residue group was
      efficiently grafted to the outer surface of SBA-15 type MSNs using a convenient
      and robust method. The cytotoxicity of SBA-15-DOPA-pCBMAs was evaluated by the 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results
      showed no significant decrease in cell viability at the tested concentration
      range. Macrophage cell uptake studies revealed that the uptake ratios of SBA-15
      DOPA-pCBMAs were much lower than that of parent MSNs. Furthermore, inductively
      coupled plasma mass spectrometry (ICP-MS) analysis results showed that after SBA
      15-DOPA-pCBMAs were conjugated with a targeting cyclo-[Arg-Gly-Asp-d-Tyr-Lys]
      (cRGD) peptide, uptake by bovine aortic endothelial cells (BAECs) was notably
      increased. Results indicated that cRGD-functionalized MSNs were able to
      selectively interact with cells expressing alphavbeta3 integrin. Thus, MSNs with
      DOPA-pCBMAs are promising as stealth multifunctional biocarriers for targeted
      drug delivery or diagnostics. 

PMID- 24670218
TI  - Nanoscopic spine localization of Norbin, an mGluR5 accessory protein.
AB  - BACKGROUND: Norbin is a neuron-specific, cytosolic protein that interacts with
      the metabotropic glutamate receptor 5 (mGluR5) and has a profound impact on
      mGluR5 signaling. Yet, little is known about its synaptic distribution. RESULTS:
      Here we have analyzed the spatial relationship between Norbin, postsynaptic
      density protein 95 (PSD-95), actin and mGluR5 in spines using super-resolution
      microscopy. Norbin was found to have a high degree of colocalization with actin
      and a lower degree of colocalization with PSD-95. Co-immunoprecipitation studies
      confirmed that interaction occurs between Norbin and actin, but not between
      Norbin and PSD-95. Norbin was also found to have a high degree of colocalization
      with the perisynaptically located mGluR5. Findings based on structured
      illumination microscopy (3D-SIM) of exogenous expressed Norbin-GFP were confirmed
      by stimulated emission depletion microscopy (STED) of immunolabeled endogenous
      Norbin. CONCLUSIONS: Norbin associates with actin rather than with PSD-95 in
      dendritic spines. Results regarding protein localization and colocalization
      performed with conventional confocal microscopy must be interpreted with great
      caution. The now available super-resolution microscopy techniques provide more
      accurate information about sub-cellular protein localization than previously was
      possible.

PMID- 24670219
TI  - Biodegradation pattern and tissue integration of native and cross-linked porcine
      collagen soft tissue augmentation matrices - an experimental study in the rat.
AB  - INTRODUCTION: Within the last decades, collagen types I and III have been
      established as a sufficient biomaterial for GBR and GTR procedures. They might
      also be an adequate matrix for soft tissue augmentations. However, collagen
      materials differ significantly regarding resorption time, biodegradation pattern
      and the invasion of inflammatory cells.The aim of the present study was to
      compare the biodegradation and tissue integration of native, differently
      processed and cross-linked collagen scaffolds in rats. METHODS: Four experimental
      porcine collagen matrices of 1.0 mm thickness, developed for soft tissue
      augmentation procedures, were tested. Based on the same native dermal Type I and
      III collagen, native (ND, Mucoderm prototype), specifically defatted (DD),
      ethylene dioxide cross-linked (ECL) and dehydrothermally cross-linked (DCL)
      dermis collagen (AAP/Botiss Biomaterials, Berlin, Germany) were evaluated. Two
      specimens of 1 * 1 cm were fixed around a non-absorbable spacer using non
      absorbable sutures. After rehydration, specimens (N = 8) were randomly allocated
      in unconnected subcutaneous pouches on the back of 40 Wistar rats. Rats were
      divided into five groups (1, 2, 4, 8 and 12 weeks), including eight animals each.
      After each period, eight rats were sacrificed and explanted specimens were
      prepared for histological analysis. The following parameters were evaluated:
      membrane thickness as a sign of biodegradation and volume stability, cell
      ingrowth, vascularization, tissue integration and foreign body reaction. RESULTS:
      Biodegradation pattern of the non cross-linked collagen scaffolds differed only
      slightly in terms of presence of inflammatory cells and cell invasion into the
      matrix. In terms of biodegradation, ECL displayed a considerable slower
      resorption than ND, DCL and DD. Chemical cross-linking using ethylene dioxide
      showed a significant higher invasion of inflammatory cells. CONCLUSION: Within
      the limits of the present study it was concluded that the processing techniques
      influenced the collagen properties in a different intensity. Dehydrothermal cross
      linking and special defatting did not notably change the biodegradation pattern,
      whereas cross-linking using ethylene dioxide led to significant higher volume
      stability of the matrix. However, ECL showed an increased inflammatory response
      and compromised tissue integration. Therefore, ethylene dioxide seems to be not
      suitable for stabilization of collagen matrices for soft tissue augmentation
      procedures.

PMID- 24670220
TI  - An Exploratory Study of Factors Associated With Sexual Inhibition and Excitation:
      Findings From a Representative Survey in Flanders.
AB  - The dual control model of sexual response was developed to account for individual
      differences in sexual excitation and inhibition. According to this model, the
      balance between excitation and inhibition is of crucial importance in determining
      an individual's sexual response to a stimulus. In this study, we aimed to
      contribute to the existing literature on sexual excitation and inhibition in two
      ways. First, we investigated the distribution of excitation and inhibition scores
      in a representative population sample. Second, we conducted an exploratory study
      of the factors associated with variation in excitation and inhibition. We used
      data from a representative survey on the sexual health of men and women in
      Flanders (N = 1,825; mean age = 43.77; SD = 17.98). The results indicated that
      excitation and inhibition had a near normal distribution among men and women.
      However, the scores for sexual inhibition due to threat of performance failure
      (SIS1) among men, and for sexual inhibition due to the threat of performance
      consequences (SIS2) among women, were somewhat skewed. Furthermore, age, gender,
      physical and mental health, education level, and attitudes toward sex were all to
      some extent associated with differences in inhibition, excitation, or both. 

PMID- 24670221
TI  - Erythema associated with pain and warmth on face and ears: a variant of
      erythermalgia or red ear syndrome?
AB  - Erythermalgia is a rare cutaneous disorder characterized by attacking of
      erythema, pain and increased temperature, which primarily involves the
      extremities and may infrequently extend to the neck, face, ears and even the
      scrotum. We reported an 18-year-old woman who presented with 3 years history of
      sole involvement of attacking erythema, pain and warmth over her face and ears
      without any other associations. The frequency and severity of the flares
      progressed gradually during the course. Cutaneous examination revealed erythema,
      increased temperature and tenderness on the face and ears during the flare. The
      symptoms could be relieved rapidly by cooling. Dermatoscope showed that vessels
      inside the erythema were more dilated during the episode than after application
      of ice. The lesion is considered a rare variant of erythermalgia with sole
      involvement of face and ears. The symptoms had mild response to oral
      antihistamines, topical steroids and tacrolimus, but had excellent response to
      the combinative therapy of aspirin and paroxetins. 

PMID- 24670222
TI  - Accelerated and increased joint damage in young mice with global inactivation of
      mitogen-inducible gene 6 after ligament and meniscus injury.
AB  - INTRODUCTION: Ligament and meniscal damage can cause joint disease. Arthritic
      joints contain increased amounts of epidermal growth factor receptor (EGFR)
      protein, and polymorphisms in EGFR are associated with arthritis risk. The role
      of endogenous EGFR regulation during joint disease due to ligament and meniscal
      trauma is unknown. Mitogen-inducible gene 6 (MIG-6) can reduce EGFR
      phosphorylation and downstream signaling. We examined the effect of EGFR
      modulation by MIG-6 on joint disease development after ligament and meniscus
      injury. METHODS: Knee ligament transection and meniscus removal were performed
      surgically on mice homozygous for a global inactivating mutation in MIG-6 (Mig-6
      /-) and in wild-type (WT) animals. RESULTS: Two weeks after surgery, Mig-6-/-mice
      had bone erosion as well as greater fibrous tissue area and serum RANKL
      concentration than WT mice. Four weeks after surgery, Mig-6-/-mice had less
      cartilage and increased cell proliferation relative to contralateral control and
      WT knees. Increased apoptotic cells and growth outside the articulating region
      occurred in Mig-6-/-mice. Tibia trabecular bone mineral density (BMD) and the
      number of trabeculae were lower in surgically treated knees relative to the
      respective control knees for both groups. BMD, as well as trabecular thickness
      and number, were lower in surgically treated knees from Mig-6-/-mice relative to
      WT surgically treated knees. Phosphorylated EGFR staining in surgically treated
      knees decreased for WT mice and increased for Mig-6-/-mice. Fewer inflammatory
      cells were present in the knees of WT mice. CONCLUSION: Mig-6-/-mice have rapid
      and increased joint damage after ligament and meniscal trauma. Mig-6 modification
      could lessen degenerative disease development after this type of injury.

PMID- 24670223
TI  - (DHQ)2AQN-catalyzed asymmetric substitution of isatin-derived hydrazones with O
      Boc-protected Morita-Baylis-Hillman adducts: A strategy for synthesizing
      enantioenriched azo compounds incorporating an oxindole scaffold.
AB  - The first example for the preparation of enantioenriched azo compounds from
      hydrazones and Morita-Baylis-Hillman adducts has been developed, affording azo
      compounds incorporating an oxindole scaffold in up to 91% yield along with a 93%
      ee value under the catalysis of (DHQ)2AQN.

PMID- 24670224
TI  - At the crossroads of violence and aggression in the emergency department:
      perspectives of Australian emergency nurses.
AB  - OBJECTIVE: Violence is widespread in Australian emergency departments (ED) and
      most prevalent at triage. The aim of the present study was to identify the causes
      and common acts of violence in the ED perceived by three distinct groups of
      nurses. METHODS: The Delphi technique is a method for consensus-building. In the
      present study a three-phase Delphi technique was used to identify and compare
      what nurse unit managers, triage and non-triage nurses believe is the prevalence
      and nature of violence and aggression in the ED. RESULTS: Long waiting times,
      drugs and alcohol all contributed to ED violence. Triage nurses also indicated
      that ED staff, including security staff and the triage nurses themselves, can
      contribute to violence. Improved communication at triage and support from
      management to follow up episodes of violence were suggested as strategies to
      reduce violence in the ED CONCLUSION :There is no single solution for the
      management of ED violence. Needs and strategies vary because people in the
      waiting room have differing needs to those inside the ED. Participants agreed
      that the introduction and enforcement of a zero tolerance policy, including
      support from managers to follow up reports of violence, would reduce violence and
      improve safety for staff. Education of the public regarding ED processes, and the
      ED staff in relation to patient needs, may contribute to reducing ED violence.
      What is known about the topic? Violence is prevalent in Australian healthcare,
      and particularly in emergency departments (ED). Several organisations and
      government bodies have made recommendations aimed at reducing the prevalence of
      violence in healthcare but, to date, these have not been implemented
      consistently, and violence continues. What does this paper add? This study
      examined ED violence from the perspective of triage nurses, nurse unit managers
      and non-triage nurses, and revealed that violence is experienced differently by
      emergency nurses, depending on their area of work. Triage nurses have identified
      that they themselves contribute to violence in the ED by their style of
      communication. Nurse unit managers and non-triage nurses perceive that violence
      is the result of drugs and alcohol, as well as long waiting times. What are the
      implications for practitioners? Strategies to reduce violence must address the
      needs of patients and staff both within the ED and in the waiting room. Such
      strategies should be multifaceted and include education of ED consumers and
      staff, as well as support from management to respond to reports of violence.

PMID- 24670225
TI  - Individual and Societal Wisdom: Explaining the Paradox of Human Aging and High
      Well-Being.
AB  - Objective: Although human aging is characterized by loss of fertility and
      progressive decline in physical abilities, later life is associated with better
      psychological health and well-being. Furthermore, there has been an unprecedented
      increase in average lifespan over the past century without corresponding
      extensions of fertile and healthy age spans. We propose a possible explanation
      for these paradoxical phenomena. Method: We reviewed the relevant literature on
      aging, well-being, and wisdom. Results: An increase in specific components of
      individual wisdom in later life may make up for the loss of fertility as well as
      declining physical health. However, current data on the relationship between
      aging and individual wisdom are not consistent and do not explain increased
      longevity in the general population during the past century. We propose that
      greater societal wisdom (including compassion) may account for the notable
      increase in average lifespan over the last century. Data in older adults with
      serious mental illnesses are limited, but suggest that many of them too
      experience improved psychosocial functioning, although their longevity has not
      yet increased, suggesting persistent stigma against mental illness and inadequate
      societal compassion. Conclusions: The proposed construct of societal wisdom needs
      more investigation. Research should also focus on the reasons for discrepant
      findings related to age-associated changes in different components of individual
      wisdom. Studies of wisdom and well-being are warranted in older people with
      serious mental illnesses, along with campaigns to enhance societal compassion for
      these disenfranchised individuals. Finally, effective interventions to enhance
      wisdom need to be developed and tested.

PMID- 24670226
TI  - Heat-shock proteins-based immunotherapy for advanced melanoma in the era of
      target therapies and immunomodulating agents.
AB  - INTRODUCTION: Heat-shock proteins (HSPs) are highly conserved, stress-induced
      proteins that function as chaperones, stabilizing proteins and delivering
      peptides. Tumor-derived HSP peptide complexes (HSPPCs) induced immunity against
      several malignancies in preclinical models, exhibiting activity across tumor
      types. AREAS COVERED: HSPPC-based vaccination showed clinical activity in subsets
      of patients with different malignancies (e.g., gastric, colorectal, pancreatic,
      ovarian cancer, and glioblastoma). In Phase III clinical trials for advanced
      melanoma and renal cell carcinoma patients, HSPPC-based vaccine demonstrated an
      excellent safety profile, thus emerging as a flexible tumor- and patient-specific
      therapeutic approach. EXPERT OPINION: Melanoma, renal clear cell carcinoma, and
      glioblastoma are among suitable targets for HSP-based treatment as demonstrated
      by immune responses and clinical activity observed in subsets of patients, mainly
      those with early stage of disease and limited tumor burden. In order to further
      improve clinical activity, combinations of HSPPC-based vaccines with mutation
      driven therapies, antiangiogenic agents, or immunomodulating monoclonal
      antibodies should be tested in controlled clinical trials.

PMID- 24670227
TI  - Structure and biological activity of 8-deoxyheronamide C from a marine-derived
      Streptomyces sp.: heronamides target saturated hydrocarbon chains in lipid
      membranes.
AB  - Polyene macrolactams are a class of microbial metabolites, many of which show
      potent biological activities with unidentified modes of action. Here we report
      that 8-deoxyheronamide C, a new 20-membered polyene macrolactam from a marine
      derived actinomycete Streptomyces sp., is a unique membrane binder. 8
      Deoxyheronamide C showed a characteristic sensitivity profile against fission
      yeast sterol mutant cells, indicating that the metabolite targets cell membranes.
      We detected tight physical interaction between heronamides including 8
      deoxyheronamide C and heronamide C and saturated hydrocarbon chains in lipid
      membranes using surface plasmon resonance experiments. We further show that
      heronamides induced abnormal cell wall morphology in fission yeast probably by
      perturbing the structure of membrane microdomains. This work will accelerate the
      biological and medical investigation of polyene macrolactams. 

PMID- 24670228
TI  - Therapeutic hypothermia for cardiovascular collapse and severe respiratory
      distress after amniotic fluid embolism.
AB  - Amniotic fluid embolism (AFE) is one of the most catastrophic complications that
      can occur during pregnancy or in the immediate postpartum period, frequently
      complicated by profound shock and cardiovascular collapse as well as severe
      respiratory distress. Therapeutic hypothermia (TH) is now commonly used to
      improve neurological outcomes after various types of hypoxic injury and is widely
      used in the treatment of postanoxic injury after cardiac arrest (CA). To our
      knowledge, no studies have evaluated whether TH could be effectively used in AFE,
      and its use for this indication has not been described previously. We describe
      the case of a 32-year-old woman, who developed clinical manifestations of AFE and
      suffered a CA in the 29th week of her pregnancy. She received prolonged CPR (40
      minutes until ROSC) and remained comatose. TH was induced and maintained for a
      total of 60 hours using an endovascular device, followed by controlled rewarming
      and maintenance of strict normothermia. The patient survived and was
      neurologically intact (CPC 1) at 6 months of follow up. 

PMID- 24670229
TI  - The suitability of EBC-Pb as a new biomarker to assess occupational exposure to
      lead.
AB  - Occupational exposure to lead (Pb) requires continuous surveillance to assure, as
      much as possible, safe and healthful working conditions. This study addresses the
      suitability of assessing Pb exposure in relevant workers using their exhaled
      breath condensate (EBC). This study enrolled workers of two different Pb
      processing industries characterized by moderate and high Pb exposure levels in
      the work environment, and a group of non-exposed individuals working in offices
      who served as baseline for Pb exposure. The EBC-Pb of workers reflected the Pb
      levels in the work environment of all three settings, although the relationship
      with B-Pb was not clear. The lack of correlation between EBC-Pb and B-Pb most
      probably indicates the time lag for Pb to enter in the two body pools. The EBC-Pb
      seems to reflect immediate exposure, providing a prompt signature of Pb in the
      environmental that may interact directly with the organ. By delivering short-term
      evaluation of exposure, EBC-Pb represents a clear advantage in biomonitoring and
      may become an interesting tool for estimating organ burden.

PMID- 24670231
TI  - Alkali-induced changes in functional properties and in vitro digestibility of
      wheat starch: the role of surface proteins and lipids.
AB  - The bread wheat starch was treated with 0.025 and 0.0625 M NaOH solution for 1,
      2, and 3 weeks at 30  degrees C, and the changes in functionality and in vitro
      digestibility were evaluated. NaOH treatment reduced protein and lipid contents
      of wheat starch from 0.46 to 0.20% and from 0.59 to 0.25%, respectively. No
      significant changes were observed in the amylose content, relative crystallinity,
      and short-range order of double helices, but there was evidence showing that
      morphology of some starch granules was altered. The swelling power and starch
      solubility of wheat starch increased from 11.4 to 14.1 g/g and from 10.9 to
      22.1%, respectively. The thermal transition temperatures were increased greatly,
      but the enthalpy change remained largely unchanged. Alkali treatment greatly
      decreased the pasting temperature, but the pasting viscosities were altered in
      different ways. The resistant starch (RS) content of wheat starch was decreased
      significantly from 69.9 to 45.2%, while the starch that is digested slowly (SDS)
      content was increased greatly from 13.6 to 34.5%. Our results showed that alkali
      treatment can significantly alter the functionality and in vitro digestibility of
      wheat starch granules by removing the surface proteins and lipids rather than
      significantly altering the internal structure of starch granules. 

PMID- 24670230
TI  - Treatment for illegal drug use disorders: the role of comorbid mood and anxiety
      disorders.
AB  - BACKGROUND: Our aim was to examine whether comorbid mood and anxiety disorders
      influence patterns of treatment or the perceived unmet need for treatment among
      those not receiving treatment for illegal drug use disorders. METHODS: Data came
      from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC,
      2001-2002 and 2004-2005, n = 34,653). Lifetime DSM-IV illegal drug use disorder
      (abuse and dependence), as well as comorbid mood (major depression, dysthymia,
      manic disorder, hypomanic disorder) and anxiety disorders (panic disorder,
      agoraphobia, social phobia, specific phobia, generalized anxiety) were
      ascertained by a standardized psychiatric interview. Treatment for illegal drug
      use disorders and perceived unmet need for treatment were assessed among
      individuals with illegal drug use disorder. Odds of treatment and odds of
      perceived unmet need for treatment were assessed using logistic regression,
      adjusting for socio-demographic characteristics, treatment for mood and anxiety
      disorders, and comorbid alcohol use disorder. RESULTS: Out of 34,653
      participants, 1114 (3.2%) had a diagnosis of lifetime illegal drug use disorder:
      21.2% had a comorbid mood disorder only, 11.8% a comorbid anxiety disorder only,
      and 45.9% comorbid mood and anxiety disorders. Comorbid mood and anxiety
      disorders were not related to treatment for illegal drug use disorders but were
      associated with an elevated likelihood of unmet need for treatment: compared to
      participants with no comorbidities, multivariate ORs were 2.21 (95% CI: 1.23-
      4.10) for mood disorder only, 2.38 (95% CI: 1.27-4.45) for anxiety disorder only,
      and 2.90 (95% CI: 1.71-4.94) for both mood and anxiety disorders. CONCLUSIONS:
      Individuals with an illegal drug use disorder and comorbid mood or anxiety
      disorders are disproportionately likely to report unmet need for treatment.
      Integrated mental health and substance use programs could prove effective in
      addressing their treatment needs.

PMID- 24670233
TI  - Recent progress in cancer therapeutics.

PMID- 24670232
TI  - New treatment option for an incomplete vertical root fracture--a preliminary case
      report.
AB  - Instead of extraction this case report presents an alternative treatment option
      for a maxillary incisor with a vertical root fracture (VRF) causing pain in a 78
      year-old patient. After retreatment of the existing root canal filling the tooth
      was stabilized with a dentine adhesive and a composite restoration. Then the
      tooth was extracted, the VRF gap enlarged with a small diamond bur and the
      existing retrograde root canal filling removed. The enlarged fracture line and
      the retrograde preparation were filled with a calcium-silicate-cement
      (Biodentine). Afterwards the tooth was replanted and a titanium trauma splint was
      applied for 12d. A 24 months clinical and radiological follow-up showed an
      asymptomatic tooth, reduction of the periodontal probing depths from 7 mm prior
      to treatment to 3 mm and gingival reattachment in the area of the fracture with
      no sign of ankylosis. Hence, the treatment of VRF with Biodentine seems to be a
      possible and promising option.

PMID- 24670234
TI  - Cervical fluid IL-6 and IL-8 levels in pregnancies complicated by preterm
      prelabor rupture of membranes.
AB  - Abstract Objective: To determine the cervical fluid interleukin (IL)-6 and IL-8
      levels in pregnancies complicated by preterm prelabor rupture of membranes
      (PPROM) and the association of these interleukins with microbial invasion of the
      amniotic cavity (MIAC) and histological chorioamnionitis (HCA). METHODS: Sixty
      women with singleton pregnancies were included in this study. Cervical fluid was
      sampled at the time of admission using Dacron polyester swabs, which were placed
      into the endocervical canal for 20 s. IL-6 and IL-8 levels were determined by
      ELISA. The management of PPROM was active management (except for in pregnancies
      <28 weeks of gestation) and occurs not later than 72 h after the rupture of
      membranes. RESULT: The women with MIAC had higher IL-6 and IL-8 levels than did
      the women without MIAC (IL-6: p=0.01; IL-8: p=0.003). There was no difference in
      IL-6 levels between women with and without HCA (p=0.37). The women with HCA had
      higher IL-8 levels only in the crude analysis (p=0.01) but not after adjustment
      for gestational age (p=0.06). The women with both MIAC and HCA had higher levels
      of IL-6 and IL-8 than did the other women (IL-6: p=0.003; IL-8: p=0.001). IL-8
      level of 2653 pg/mL was found to be the best cut-off point in the identification
      of PPROM pregnancies complicated by both MIAC and HCA with a likelihood ratio of
      24. CONCLUSIONS: The presence of MIAC is the most important factor impacting the
      local cervical inflammatory response, which is determined by IL-6 and IL-8 levels
      in the cervical fluid. IL-8 levels seem to be a promising non-invasive marker for
      the prediction of pregnancies complicated by the presence of both MIAC and HCA.

PMID- 24670235
TI  - CRP levels in extremely low birth weight (ELBW) septic infants.
AB  - OBJECTIVE: Testing the validity of C-reactive protein (CRP) in extremely low
      birth weight (ELBW) infants. METHODS: During a five-year period, 483 infants with
      probable (36%) and definite sepsis (64%) were enrolled in the study. RESULTS:
      ELBW infants with definitive sepsis had CRP levels comparable with full-terms
      (p=0.992). However, the highest (hs) values were observed in infants >2500 g, 24
      h after the septic work up whereas in those with birth weight (BW) <1000 g after
      48 h. Highest CRP levels of infants with early sepsis were similar to those of
      the late onset ones (p=0.825). The causative microorganism had a strong influence
      on CRP values, as Gram negative germs produced significantly higher CRP levels in
      comparison to infants with Gram positive sepsis. CONCLUSIONS: Highest CRP values
      in <1000 g infants increase in levels comparable to full terms, but with a 24-h
      delay.

PMID- 24670236
TI  - Assessment of free fetal DNA concentration in maternal plasma during the first
      trimester of pregnancy: comparative study between EDTA and PPT tubes - pilot
      study.
AB  - OBJECTIVE: To compare ethylenediamine tetraacetic acid (EDTA) tubes and plasma
      preparation tubes (PPT) for evaluating maternal plasma during the first trimester
      of pregnancy. METHODS: A cross-sectional study was conducted on 24 male fetuses
      in women between 6 and 14 weeks of pregnancy. Blood samples (10 mL) were
      collected and stored in EDTA and PPT tubes. Subsequently, the samples were
      centrifuged and sent for free fetal DNA extraction by means of the polymerase
      chain reaction (PCR) technique. The reactions were performed in a real time PCR
      machine for detecting the amplification products. The genome region chosen for
      performing the PCR reactions was a target specific for the Y chromosome, in which
      the DYS-14 marker was amplified only when the DNA was of male sex. The free fetal
      DNA concentration was given by the threshold cycle (TC). To compare the tubes,
      the paired Student t-test was used. RESULTS: The mean gestational age was 11.08
      +/- 2.30 weeks (range: 6-14). The mean TC for PPT was 30.08 +/- 1.05 (range:
      27.08-32.61) and for EDTA, 30.23 +/- 0.96 (range: 28.01-32.09), but without
      statistical significance (p=0.357). CONCLUSION: We did not observe any
      statistically significant difference in free fetal DNA concentration between the
      EDTA and PPT tubes.

PMID- 24670238
TI  - Fetal nuchal fold thickness measurement between 18 and 24 weeks of pregnancy:
      reference intervals for a Brazilian population.
AB  - OBJECTIVE: To determine reference intervals of fetal nuchal fold (NF) thickness
      measurement in the second trimester of pregnancy in a Brazilian population.
      METHODS: This was a retrospective cross-sectional study with 2559 normal
      singleton pregnancies between 18 and 24 weeks of pregnancy. The fetal NF was
      obtained in the axial plane of fetal head at level of lateral ventricles
      including the cavum septum pellucidum, third ventricle, thalamus and transverse
      cerebellar diameter. The NF was measured posterior to the occipital bone, from
      the bone surface to the skin, including only soft tissue. To assess the
      correlation between fetal NF and gestational age (GA), polynomial equations were
      calculated and adjusted to determination coefficient (R(2)). RESULTS: The mean
      fetal NF ranged from 3.98 +/- 1.14 mm at 18-18+6 to 4.83 +/- 0.93 mm at 24-24+6
      weeks of gestation. A good correlation was observed between fetal NF and GA,
      which is better represented by a linear equation: NF=1.055+0.158*GA (R(2) =0.06).
      CONCLUSION: Reference intervals of fetal NF thickness measurement in the second
      trimester of pregnancy were determined for a Brazilian population.

PMID- 24670237
TI  - Neonatal outcome following new assisted reproductive technology regulations in
      Turkey - a nationwide multicenter point prevalence study.
AB  - OBJECTIVE: In March 2010, a new legislation about assisted reproductive
      technology (ART) activities, favoring single embryo transfer, was introduced in
      Turkey. Consequences of new regulations on neonatal outcome have not been
      evaluated in multicenter studies yet. In this study, our aim was to evaluate
      neonatal outcome of infants from medically assisted reproduction (MAR)
      pregnancies in the post-legislation era. METHODS: A point prevalence study was
      conducted at 51 centers in Turkey on 1 April 2013. Data about fertility
      treatments and neonatal characteristics were evaluated for "live births" (Group
      1) and "patients being cared in the NICU" (Group 2). RESULTS: Seventeen (4%) of
      420 infants in group 1, and 89 (8.1%) of 1094 infants in group 2 were born after
      MAR pregnancies. The ratio of multiple births in MAR pregnancies was still very
      high as 47.1% for group 1, 69.1% for group 2 infants. MAR babies constituted 9.9%
      of infants in Level 3 NICUs and 7.6% infants in Level 2 NICUs. MAR was associated
      with increased risk of multiple births and prematurity. CONCLUSIONS: After the
      new legislation, multiple birth rates are still high in MAR pregnancies,
      resulting in unfavorable neonatal outcomes. Efforts to decrease multiple birth
      rates should be encouraged.

PMID- 24670240
TI  - Neonatal morphine in extremely and very preterm neonates: its effect on the
      developing brain - a review.
AB  - OBJECTIVE: Preterm infants requiring intensive care experience a large number of
      stressful and painful procedures. Management of stress and pain is therefore an
      important issue. This review provides an overview of the research on the use of
      morphine and its neurodevelopmental effects on this vulnerable group of neonates.
      METHODS: A structural literature search of both experimental and clinical data
      has been done using an electronic database (PubMed), but also relevant reference
      lists and related articles were used. RESULTS: A total of 39 sources were
      considered relevant for this review to elucidate the effects of morphine on the
      developing brain. The results showed that both animal experimental and clinical
      data displayed conflicting results on the effects of neonatal morphine on
      neurodevelopmental outcome. However, in contrast to specific short-term
      neurological outcomes long-term neurodevelopmental outcome does not seem to be
      adversely affected by morphine. CONCLUSION: After a careful review of the
      literature, no definite conclusions concerning the effects of neonatal morphine
      on the long-term neurodevelopmental outcome in extremely premature neonates can
      be drawn. More prospectively designed trials should be conducted using reliable
      and validated pain assessment scores to evaluate effects of morphine on long-term
      neurodevelopmental outcome to demonstrate a beneficial or adverse effect of
      morphine in preterm infants.

PMID- 24670239
TI  - Pregnancy and delivery in women with esophageal varices due to hepatic vein
      thrombosis.
AB  - AIM: Retrospective analysis of the course of pregnancy, labor and mode of
      anesthesia in women with portal hypertension and esophageal varices induced by
      portal vein thrombosis. MATERIAL: From 2000 to 2012 seven pregnant were admitted.
      None had liver transplantation (Ltx), the varicose have been in the 1st stage.
      Each of them has been consulted by the obstetrician, transplant surgeon and
      anesthetist. The patient condition during pregnancy, labor and postpartum period
      was analyzed. RESULTS: Pregnancy in five cases proceeded physiologically. In one
      threatening miscarriage was diagnosed and treated with gestagens, two patients
      had tocolytic. One required variceal banding twice. In three thrombocytopenia
      worsened, with platelet count <70 g/L (up to 59 g/L). They received platelet
      transfusion before delivery. In one case, significant hipoproteinemia (4.7 g/L)
      occurred. In a case, GDM G1 and oligohydramnios were found. All women delivered
      at term (37-40 Hbd). In all general anesthesia with the use of remifentanil was
      done. There were no fluctuations in MAP and HR. Incision to delivery time was 2.5
      min. Time from opioid administration to birth was <4 min. All children were born
      in good condition, weight 10-90 percentile. Regional anesthesia is
      contraindicated in patients with thrombocytopenia. In patients with esophageal
      varices sudden increase in heart rate and blood pressure can cause hemorrhage.
      CONCLUSION: Patients with portal hypertension can deliver at term. It is a high
      risk pregnancy. In this group it is desirable to shorten the second stage of
      labor or complete it by c-section under general anesthesia with remifentanyl
      which allows getting desired analgesia without complications in the newborn.
      Surveillance of pregnant with portal hypertension must include monitoring of
      liver function and coagulation disorders.

PMID- 24670241
TI  - Context-dependent redox properties of natural phenolic materials.
AB  - Macromolecular phenolics are among the most abundant organic molecules in nature,
      yet their biological activities are largely unresolved because of their
      structural complexity and because of an inability to probe their functionality
      experimentally. We developed thin film and electrochemical methodologies to probe
      the redox properties of melanin, lignin, and humic acid, three of the most
      abundant phenolic materials. We observed that all three phenolic matrixes possess
      redox activity and can be repeatedly switched between oxidized and reduced
      states. Furthermore, we observed that melanin possesses pro-oxidant activities
      exemplified by the uncatalyzed generation of reactive oxygen species (ROS) upon
      exposure to air; however, this pro-oxidant activity is observed only for melanin
      films that are poised in their reduced state. Conversely, melanin's antioxidant
      radical-scavenging activities are insensitive to its redox state. These results
      demonstrate that natural phenolic matrixes are not inert but rather serve as open
      source redox media with significant potential for impacting redox signaling and
      redox biology. 

PMID- 24670242
TI  - Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from
      Southern Thailand.
AB  - BACKGROUND: Drug resistance in Plasmodium falciparum is a major problem in
      malaria control especially along the Thai-Myanmar and Thai-Cambodia borders. To
      date, a few molecular markers have been identified for anti-malarial resistance
      in P. falciparum, including the P. falciparum chloroquine resistance transporter
      (pfcrt) and the P. falciparum multidrug resistance 1 (pfmdr1). However no
      information is available regarding the distribution pattern of these gene
      polymorphisms in the parasites from the Thai-Malaysia border. This study was
      conducted to compare the distribution pattern of the pfcrt and pfmdr1
      polymorphisms in the parasites from the lower southern provinces, Thai-Malaysia
      border and the upper southern provinces, Thai-Myanmar border. In addition, in
      vitro sensitivities of anti-malarial drugs including chloroquine, mefloquine,
      quinine, and artesunate were determined. METHODS: In all, 492 P. falciparum
      positive blood samples were collected from the lower southern provinces:
      Songkhla, Yala and Narathiwas. From the upper southern part of Thailand, Ranong
      and Chumphon, 66 samples were also collected. Polymorphisms of the pfcrt and the
      pfmdr1 gene were determined using PCR techniques. In vitro sensitivities of anti
      malarial drugs were determined using radioisotopic method. RESULTS: All parasites
      from both areas contained the pfcrt 76 T allele. The pfmdr1 86Y allele was
      significantly more common in the parasites isolated from the lower southern
      areas. In contrast, the pfmdr1 184F allele was predominant among the parasites
      from the upper southern areas especially Ranong. In addition, the parasites from
      Ranong contained higher copy numbers than the parasites from other provinces. All
      adapted parasite isolates exhibited CQ-resistant phenotype. Neither QN nor MQ
      resistance was detected in these isolates. CONCLUSION: The parasites from Thai
      Malaysia border exhibited different resistant patterns compared to other areas
      along the international border of Thailand. This information will be useful for
      anti-malarial drug policy in Thailand.

PMID- 24670244
TI  - Activation of protease-activated receptor 2 reduces glioblastoma cell apoptosis.
AB  - BACKGROUND: The pathogenesis of glioma is unclear. The disturbance of the
      apoptosis process plays a critical role in glioma growth. Factors regulating the
      apoptosis process are to be further understood. This study aims to investigate
      the role of protease activated receptor-2 (PAR2) in regulation the apoptosis
      process in glioma cells. RESULTS: The results showed that U87 cells and human
      glioma tissue expressed PAR2. Exposure to tryptase, or the PAR2 active peptide,
      increased STAT3 phosphorylation in the radiated U87 cells, reduced U87 cell
      apoptosis, suppressed the expression of p53 in U87 cells. CONCLUSIONS: Activation
      of PAR2 can reduce the radiated U87 cell apoptosis via modulating the expression
      of p53. The results implicate that PAR2 may be a novel therapeutic target in the
      treatment of glioma.

PMID- 24670243
TI  - Initiating a regenerative response; cellular and molecular features of wound
      healing in the cnidarian Nematostella vectensis.
AB  - BACKGROUND: Wound healing is the first stage of a series of cellular events that
      are necessary to initiate a regenerative response. Defective wound healing can
      block regeneration even in animals with a high regenerative capacity.
      Understanding how signals generated during wound healing promote regeneration of
      lost structures is highly important, considering that virtually all animals have
      the ability to heal but many lack the ability to regenerate missing structures.
      Cnidarians are the phylogenetic sister taxa to bilaterians and are highly
      regenerative animals. To gain a greater understanding of how early animals
      generate a regenerative response, we examined the cellular and molecular
      components involved during wound healing in the anthozoan cnidarian Nematostella
      vectensis. RESULTS: Pharmacological inhibition of extracellular signal-regulated
      kinases (ERK) signaling blocks regeneration and wound healing in Nematostella. We
      characterized early and late wound healing events through genome-wide microarray
      analysis, quantitative PCR, and in situ hybridization to identify potential wound
      healing targets. We identified a number of genes directly related to the wound
      healing response in other animals (metalloproteinases, growth factors,
      transcription factors) and suggest that glycoproteins (mucins and uromodulin)
      play a key role in early wound healing events. This study also identified a novel
      cnidarian-specific gene, for a thiamine biosynthesis enzyme (vitamin B
      synthesis), that may have been incorporated into the genome by lateral gene
      transfer from bacteria and now functions during wound healing. Lastly, we suggest
      that ERK signaling is a shared element of the early wound response for animals
      with a high regenerative capacity. CONCLUSIONS: This research describes the
      temporal events involved during Nematostella wound healing, and provides a
      foundation for comparative analysis with other regenerative and non-regenerative
      species. We have shown that the same genes that heal puncture wounds are also
      activated after oral-aboral bisection, indicating a clear link with the
      initiation of regenerative healing. This study demonstrates the strength of using
      a forward approach (microarray) to characterize a developmental phenomenon (wound
      healing) at a phylogenetically important crossroad of animal evolution (cnidarian
      bilaterian ancestor). Accumulation of data on the early wound healing events
      across numerous systems may provide clues as to why some animals have limited
      regenerative abilities.

PMID- 24670245
TI  - Gene circuit performance characterization and resource usage in a cell-free
      "breadboard".
AB  - The many successes of synthetic biology have come in a manner largely different
      from those in other engineering disciplines; in particular, without well
      characterized and simplified prototyping environments to play a role analogous to
      wind-tunnels in aerodynamics and breadboards in electrical engineering. However,
      as the complexity of synthetic circuits increases, the benefits--in cost savings
      and design cycle time--of a more traditional engineering approach can be
      significant. We have recently developed an in vitro "breadboard" prototyping
      platform based on E. coli cell extract that allows biocircuits to operate in an
      environment considerably simpler than, but functionally similar to, in vivo. The
      simplicity of this system makes it a promising tool for rapid biocircuit design
      and testing, as well as for probing fundamental aspects of gene circuit operation
      normally masked by cellular complexity. In this work, we characterize the cell
      free breadboard using real-time and simultaneous measurements of transcriptional
      and translational activities of a small set of reporter genes and a
      transcriptional activation cascade. We determine the effects of promoter
      strength, gene concentration, and nucleoside triphosphate concentration on
      biocircuit properties, and we isolate the specific contributions of essential
      biomolecular resources-core RNA polymerase and ribosomes-to overall performance.
      Importantly, we show how limits on resources, particularly those involved in
      translation, are manifested as reduced expression in the presence of orthogonal
      genes that serve as additional loads on the system.

PMID- 24670246
TI  - The development and deployment of integrated electronic care records in a
      regional adult and paediatric cystic fibrosis unit.
AB  - BACKGROUND: Electronic care records (ECRs) for cystic fibrosis (CF) provide a
      basis for accurate, reliable capture of clinical measures and interventions, and
      epidemiological trends, providing the basis for improved efficiency and patient
      safety. METHODS: A primary care system was modified for hospital use and clinical
      codes devised for all aspects of CF care. Performance and usability were
      assessed. RESULTS: Of a total of 620 patients 619 consented to their data being
      recorded in the system. Five hundred and twenty three new codes were created and
      embedded behind 60 new templates. Following introduction of ECR, completion of
      annual assessments increased from 43% to 92%, retrieval of drug costs rose
      significantly and time to correspondence with primary care fell from 34days to
      <2days. Staff satisfaction was high. CONCLUSION: The system is fully operational
      allowing the unit to function as a paperless service. Efficiencies of staffing
      activity, process management and cost retrievals are evident. Sharing of coding
      structures is important in future care.

PMID- 24670247
TI  - Animal models of urinary bladder cancer and their application to novel drug
      discovery.
AB  - INTRODUCTION: Urinary bladder cancer is a major human malignancy that afflicts
      millions of people worldwide every year. Urinary bladder cancer is usually
      superficial at presentation in 70 - 80% of patients. In these cases, a simple
      transurethral resection is adequate for removing the tumor. However, some
      patients experience recurrence or even tumor progression. In another 20 - 30% of
      patients, muscle-invasive carcinoma is diagnosed. Despite all the developments in
      this area, even today, the options for treatment of urinary bladder cancer remain
      inadequate. The search for the mechanisms involved in human urinary bladder
      cancer and for new and improved treatment methods has led to the development of
      many experimental models using laboratory animals over the past 40 years. AREAS
      COVERED: In this review, the authors provide a concise overview of the animal
      models used to study urinary bladder cancer. Furthermore, the authors discuss
      their advantages and disadvantages with regard to the search for new therapeutic
      approaches. EXPERT OPINION: The use of urinary bladder cancer models for
      understanding the mechanisms involved in tumors' response to new treatments is an
      important step in the drug discovery process. However, the authors believe that
      it will be necessary to develop our knowledge and understanding of the molecular
      processes underlying urothelial chemical carcinogenesis for us to better evaluate
      the efficacy of novel therapeutics.

PMID- 24670248
TI  - Differential developmental profiles of adolescents using sexually explicit
      internet material.
AB  - This study used a person-centered approach to examine whether different
      developmental trajectories of boys' and girls' use of sexually explicit Internet
      material (SEIM) exist, which factors predict these trajectories, and whether
      sexual behavior develops differently for adolescents in these trajectories. A
      combination of latent class growth analysis on SEIM use and latent growth curve
      analysis on sexual behavior was used on four-wave longitudinal data of 787 eighth
      through tenth grade Dutch adolescents. Among boys, four SEIM use trajectories
      were identified, which were labeled Nonuse/Infrequent Use, Strongly Increasing
      Use, Occasional Use, and Decreasing Use. Among girls, a large Stable
      Nonuse/Infrequent Use and smaller Strongly Increasing Use and Stable Occasional
      Use trajectories were distinguished. Higher initial levels and/or stronger
      increases in SEIM use were predicted by demographic, social contextual, personal,
      and media use characteristics, including a stronger sexual interest, a higher
      degree of perceived realism regarding sexualized Internet content, and more
      permissive sexual attitudes. Moreover, initial levels of and, to some extent,
      developmental changes in sexual behavior varied for boys and girls in the
      different SEIM use trajectories. Whereas some adolescents showed concurrent low
      levels, or parallel strong increases in SEIM use and sexual behavior, a subgroup
      of boys decreased their SEIM use while increasing their sexual behavior. 

PMID- 24670250
TI  - First impressions: towards becoming a health-literate health service.
AB  - A 'health-literate organisation' recognises that miscommunication is very common
      and can negatively affect consumer care and outcomes, and makes it easier for
      people to navigate, understand, and use health information and services. This
      paper reports on the First Impressions Activities conducted by consumers to
      assess aspects of the literacy environment of a rural health service. The First
      Impressions Activities consists of three tools to assist health services to begin
      to consider some of the characteristics of their organisation that help and
      hinder a consumer's ability to physically navigate their way to and about the
      health service. The results show that navigation to and within the rural health
      service was made more complex due to lack of information, difficulty finding
      information, inconsistent terminology used in signage, missing signage, signage
      obscured by foliage, and incorrect signage. 

PMID- 24670249
TI  - Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde
      dehydrogenase/disialoganglioside identify their tumor stem cells.
AB  - INTRODUCTION: Although breast phyllodes tumors are rare, there is no effective
      therapy other than surgery. Little is known about their tumor biology. A
      malignant phyllodes tumor contains heterologous stromal elements, and can
      transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile
      properties prompted us to explore their possible relationship to mesenchymal stem
      cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in
      phyllodes tumors. METHODS: Paraffin sections of malignant phyllodes tumors were
      examined for various markers by immunohistochemical staining. Xenografts of human
      primary phyllodes tumors were established by injecting freshly isolated tumor
      cells into the mammary fat pad of non-obese diabetic-severe combined
      immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were
      sorted into various subpopulations by flow cytometry and examined for their in
      vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and
      their ability to undergo differentiation. RESULTS: Immunohistochemical analysis
      revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166,
      CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH),
      and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2,
      vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to
      different extents. Four xenografts were successfully established from human
      primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed
      approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+
      cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells
      displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In
      vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold
      higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being
      sufficient for engraftment. Moreover, we provided the first evidence for the
      induction of ALDH+/GD2+ cells to differentiate into neural cells of various
      lineages, along with the observation of neural differentiation in clinical
      specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells
      could also be induced to differentiate into adipocytes, osteocytes or
      chondrocytes. CONCLUSIONS: Our findings revealed that malignant phyllodes tumors
      possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and
      ALDH+/GD2+ subpopulations.

PMID- 24670251
TI  - Course of post-traumatic stress disorder and health care utilisation among
      resettled refugees in the Netherlands.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a major health problem among
      refugees worldwide. After resettlement, the prevalence of PTSD remains high
      despite the fact that various PTSD treatments are known to be effective. METHODS:
      We examined the course of PTSD and the role of mental health care utilisation at
      a 7-year interval (2003-2010) among a cohort of refugees from Iran, Afghanistan,
      and Somalia after resettlement in the Netherlands. RESULTS: The unchanged high
      prevalence of PTSD (16.3% in 2003 and 15.2% in 2010) was attributable in part to
      late onset of PTSD symptoms (half of the respondents with PTSD at T2 were new
      cases for whom PTSD developed after 2003). The second reason concerned the low
      use of mental health care services at T1. Whereas the multivariate analyses
      showed the effectiveness of mental health care, only 21% of respondents with PTSD
      at T1 had had contact with a mental health care provider at that time. Use of
      mental health care during the first wave increased the odds of improvement in
      PTSD symptoms between both measurements (OR 7.58, 95% CI 1.01; 56.85).
      CONCLUSIONS: The findings of this study suggest there are two possible
      explanations for the persistently high prevalence of PTSD among refugees. One is
      the late onset of PTSD and the other is the low utilisation of mental health
      care. Health care professionals should be aware of these issues, especially given
      the effectiveness of mental health care for this condition.

PMID- 24670253
TI  - An exploration of cultural beliefs and practices across the Southern Ground
      Hornbill's range in Africa.
AB  - BACKGROUND: This article explores cultural beliefs and practices related to the
      Southern Ground-Hornbill (SGH) (Bucorvus leadbeateri) in nine southern and east
      African countries. METHODS: A qualitative, thematic content-analysis approach was
      followed. Ninety-eight participants took part in the study. Interviews and group
      discussions were used as the main data gathering methods. Each interview was
      digitally recorded and transcribed. Data were analysed by means of thematic
      content analysis. RESULTS: The main themes that emerged from the data analysis
      indicated that beliefs and practices relate to the SGH as being (a) a bringer or
      signifier of death/destruction/loss/ deprivation, with the bird commonly being
      regarded as a bad omen of evil spirits and announcer of calamities; (b) a
      protector against evil spirits, against lightning and against drought; (c) an
      enabler/causer of altered perceptions, which include remote viewing, foreseeing
      the future, and creating an illusion; and (d) a timekeeper that announces the
      beginning and end of a working day and of seasonal changes. CONCLUSIONS:
      Knowledge about the use of the SGH in cultural practices can contribute to
      conservation efforts in at least two significant ways: Firstly, beliefs and
      practices that were identified in this study as having potentially protective
      consequences for the SGH can now be specifically targeted and strengthened in
      future interventions. Secondly, destructive beliefs and practices that were
      identified can now be changed by means of the implementation of an intervention
      programme in countries where it is needed.

PMID- 24670252
TI  - Relationships between starch synthase I and branching enzyme isozymes determined
      using double mutant rice lines.
AB  - BACKGROUND: Starch is the most important carbohydrate in plant storage tissues.
      Multiple isozymes in at least four enzyme classes are involved in starch
      biosynthesis. Some of these isozymes are thought to interact and form complexes
      for efficient starch biosynthesis. Of these enzyme classes, starch synthases
      (SSs) and branching enzymes (BEs) play particularly central roles. RESULTS: We
      generated double mutant lines (ss1/be1 and ss1L/be2b) between SSI (the largest
      component of total soluble SS activity) and BEI or BEIIb (major BEs in developing
      rice endosperm) to explore the relationships among these isozymes. The seed
      weight of ss1/be1 was comparable to that of wild type, although most ss1/be2b
      seeds were sterile and no double recessive plants were obtained. The seed weight
      of the double recessive mutant line ss1L/be2b, derived from the leaky ss1 mutant
      (ss1L) and be2b, was higher than that of the single be2b mutant. Analyses of the
      chain-length distribution of amylopectin in ss1/be1 endosperm revealed additive
      effects of SSI and BEI on amylopectin structure. Chain-length analysis indicated
      that the BEIIb deficiency significantly reduced the ratio of short chains in
      amylopectin of ss1L/be2b. The amylose content of endosperm starch of ss1/be1 and
      ss1L/be2b was almost the same as that of wild type, whereas the endosperm starch
      of be2b contained more amylose than did that of wild type. SSI, BEI, and BEIIb
      deficiency also affected the extent of binding of other isozymes to starch
      granules. CONCLUSIONS: Analysis of the chain-length distribution in amylopectin
      of the double mutant lines showed that SSI and BEI or BEIIb primarily function
      independently, and branching by BEIIb is followed by SSI chain elongation. The
      increased amylose content in be2b was because of reduced amylopectin
      biosynthesis; however, the lower SSI activity in this background may have
      enhanced amylopectin biosynthesis as a result of a correction of imbalance
      between the branching and elongation found in the single mutant. The fact that a
      deficiency of SSI, BEI, or BEIIb affected the affinity of other starch
      biosynthetic isozymes for the starch granule implies that there is a close
      interaction among SSI, BEI and BEIIb during amylopectin biosynthesis in rice
      endosperm.

PMID- 24670254
TI  - Enhanced microbial diversity in the saliva microbiome induced by short-term
      probiotic intake revealed by 16S rRNA sequencing on the IonTorrent PGM platform.
AB  - Microbial communities populating several human body habitats are important
      determinants of human health. Cultivation-free community-wide approaches like
      bacterial 16S rRNA sequencing recently revolutionized the study of such human
      associated microbial diversity, and the continuously decreasing cost/throughput
      ratio of current sequencing platforms is further enhancing the availability and
      effectiveness of microbiome research. The IonTorrent PGM platform is among the
      latest available commercial high-throughput sequencing tools, but it is just
      starting to be used for 16S rRNA surveys with only episodic assessments of its
      performance. We present here the first IonTorrent profiling of the human saliva
      microbiome collected from 12 healthy individuals. In this cohort, a subset of the
      volunteers was asked to assume a probiotic product, in order to investigate its
      impact on the composition and the structure of the saliva microbiome. Analysis of
      the generated dataset suggests the suitability of the IonTorrent platform for 16S
      rRNA surveys, even though some platform-specific choices are required to optimize
      the consistency of the obtained bacterial profiles. Interestingly, we found a
      marked and statistically significant increase of the overall bacterial diversity
      in the saliva of individuals who received the probiotic product compared to the
      control group, suggesting a short-term effect of probiotic product administration
      on oral microbiome composition. 

PMID- 24670255
TI  - Dynamic stabilization: a nidus for infection?
AB  - INTRODUCTION: Dynamic stabilization offers an adjunct to fusion with motion
      preservation. In comparison, standard instrumented fusion (if) consists of
      titanium screws and rods/plates, which do not allow for motion at the level of
      the fusion. The reported infection rate following a standard if ranges from 0.2%
      to 7%. METHODS: a retrospective chart review of 142 patients who underwent
      posterior lumbar stabilization procedures was conducted. Ten patients received
      dynamic stabilization and 132 patients had a standard if. Rates of infection,
      requiring hardware removal, were compared between the aforementioned groups.
      RESULTS: Of the 132 patients undergoing posterior if, three developed a deep
      wound infection requiring removal of hardware (2.3%). Of the 10 patients
      undergoing dynamic stabilization, three developed a deep wound infection (30%)
      with 2 requiring removal of hardware (20%), secondary to persistent deep wound
      infection or osteomyelitis at the pedicle screw sites. There was a significantly
      increased risk of deep wound infection (p < 0.0001) with the use of dynamic
      stabilization compared to standard if. CONCLUSIONS: Our series demonstrates that
      the infection rate in patients undergoing dynamic stabilization is higher than
      the infection rate for instrumented fusion without a significant difference in
      comorbidity scores. We postulate that the polycarbonate urethane spacer acts as a
      medium for bacteria, whereas the titanium screws and rods are smooth, solid, and
      inert, resulting in a lower risk of infection.

PMID- 24670257
TI  - Predictive factors of post-operative myasthenic crisis after thymectomy: the role
      of surgical invasiveness.

PMID- 24670256
TI  - Serotonin depletion can enhance the cerebrovascular responses induced by cortical
      spreading depression via the nitric oxide pathway.
AB  - Serotonin (5-HT) is an important neurotransmitter involved in the control of
      neural and vascular responses. 5-HT depletion can induce several neurological
      disorders, including migraines. Studies on a cortical spreading depression (CSD)
      migraine animal model showed that the cortical neurons sensitivity, vascular
      responses, and nitric oxide (NO) production were significantly increased in 5-HT
      depletion. However, the involvement of NO in the cerebrovascular responses in 5
      HT depletion remains unclear. This study aimed to investigate the role of NO in
      the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were
      divided into four groups: control, control with L-NAME treatment, 5-HT depleted,
      and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by
      intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the
      experiment. The CSD was triggered by KCl application. After the second wave of
      CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously
      injected into the rats with or without L-NAME treatment groups, respectively. The
      intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1),
      and the ultrastructural changes of the cerebral microvessels were examined. The
      results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1
      expressions in the cerebral cortex. The number of endothelial pinocytic vesicles
      and microvilli was higher in the 5-HT depleted group when compared to the
      control. Interestingly, L-NAME treatment significantly reduced the abnormalities
      observed in the 5-HT depleted group. The results of this study demonstrated that
      an increase of NO production is one of the mechanisms involved in the CSD-induced
      alterations of the cerebrovascular responses in 5-HT depletion.

PMID- 24670258
TI  - Different effects of etomidate and propofol on memory in immature rats.
AB  - This study is to investigate the effects of etomidate and propofol on memory and
      possible involved mechanisms using immature rats. Forty-eight rats randomly
      received intraperitoneal injection of 5 mg/kg etomidate (n = 16), 50 mg/kg
      propofol (n = 16) or normal saline (control, n = 16). Three hours after
      awakening, memory was assessed by Y-maze test using 10 rats in each drug group.
      Gamma-aminobutyric acid (GABA) content in hippocampal tissue was measured using
      six rats in each group. Etomidate group had more total reaction time (TRT)
      compared with the control group in Y-maze test ( p < 0.05). No other difference
      between these two groups was observed. Propofol group had less number of correct
      response ( p < 0.01) and more TRT ( p < 0.05) in Y-maze test, as well as more
      GABA concentration detected in hippocampal tissue ( p < 0.01) than the control
      group. Propofol group also showed less number of correct response ( p < 0.05) and
      more hippocampal GABA concentration ( p < 0.01) compared with etomidate group.
      Etomidate does not show significant effects on memory in rat and further
      investigation is required. Propofol can affect memory in rat possibly via
      increasing the synthesis and/or secretion of GABA as one of the factors.

PMID- 24670259
TI  - Transport of Egg White ACE-Inhibitory Peptide, Gln-Ile-Gly-Leu-Phe, in Human
      Intestinal Caco-2 Cell Monolayers with Cytoprotective Effect.
AB  - The purpose of this study was to investigate the transepithelial transport and
      cytoprotective effect of Gln-Ile-Gly-Leu-Phe (QIGLF), an ACE-inhibitory peptide
      derived from egg white ovalbumin, in human intestinal Caco-2 cell monolayers. The
      results showed that QIGLF could be absorbed intact through Caco-2 cell monolayers
      with a Papp value of (9.11 +/- 0.19) * 10-7 cm/s (transport kinetic parameters:
      Km, 32.37 +/- 12.59 mM; Vmax, 1.23 +/- 0.49 MUM/min cm2). The transport was not
      significantly decreased by sodium azide and Gly-Pro, an ATP synthesis inhibitor
      and a peptide transporter 1 (PepT1) substrate, respectively, suggesting that
      transport of QIGLF was not energy-dependent and carrier-mediated. In addition,
      wortmannin, a transcytosis inhibitor, had little effect on the transport,
      suggesting that endocytosis was not involved in the transport of QIGLF. However,
      the transport of QIGLF was increased significantly in the presence of
      cytochalasin D, a tight junction disruptor, suggesting that paracellular
      transport via tight junctions was the major transport mechanism for intact QIGLF
      across Caco-2 cell monolayers. Moreover, QIGLF was added to Caco-2 cells followed
      by addition of H2O2, and exhibited significant cytoprotective effect in Caco-2
      cells against oxidative stress induced by H2O2.

PMID- 24670260
TI  - General observation of lithium intercalation into graphite in ethylene-carbonate
      free superconcentrated electrolytes.
AB  - Lithium-ion batteries have exclusively employed an ethylene carbonate (EC)-based
      electrolyte to ensure the reversibility of the graphite negative electrode
      reaction. Because of the limitation of electrolyte compositions, there has been
      no remarkable progress in commercial lithium-ion batteries despite active
      research on positive electrode materials. Herein, we present a salt
      superconcentrating strategy as a simple and effective method of universalizing a
      graphite negative electrode reaction in various organic solvents. A dilute
      electrolyte (e.g., 1 mol dm(-3)) of sulfoxide, ether, and sulfone results in
      solvent cointercalation and/or severe electrolyte decomposition at a graphite
      electrode, whereas their superconcentrated electrolyte (e.g., >3 mol dm(-3))
      allows for highly reversible lithium intercalation into graphite. We have found a
      unique coordination structure in the superconcentrated solution and an anion
      based inorganic SEI film on the cycled graphite electrode, which would be the
      origin of the reversible graphite negative electrode reaction without EC. Our
      salt-superconcentrating strategy, expanding the graphite negative electrode
      reaction in various organic solvents other than EC, will contribute to the
      development of advanced lithium-ion batteries with high-voltage and fast-charging
      characters based on new EC-free functional electrolytes. 

PMID- 24670261
TI  - A new approach for the one-step synthesis of bioactive PS vs. PMMA silica hybrid
      microspheres as potential drug delivery systems.
AB  - In this work, hybrid microspheres were prepared in a two-step process combining
      the emulsifier free-emulsion polymerization and the sol-gel coating method. In
      the first step, polystyrene (St) and poly(methyl methacrylate) (PMMA)
      microspheres were prepared as sacrificial template and in the second step a
      silanol shell was fabricated. The functionalized surface of the hybrid
      microspheres by silane analogs (APTES, TEOS) resulted in enhanced effects. The
      hollow microspheres were resulted either in an additional step by template
      dissolution and/or during the coating process. The microspheres' surface
      interactions and the size distribution were optimized by treatment in simulated
      body fluids, which resulted in the in vitro prediction of bioactivity. The
      bioassay test indicated that the induced hydroxyapatite resembled in structure to
      naturally occurring bone apatite. The drug doxorubicin (DOX) was used as a model
      entity for the evaluation of drug loading and release. The drug release study was
      performed in two different pH conditions, at acidic (pH=4.5) close to cancer cell
      environment and at slightly basic pH (pH=7.4) resembling the orthopedic
      environment. The results of the present study indicated promising hybrid
      microspheres for the potential application as drug delivery vehicles, for dual
      orthopedic functionalities in bone defects, bone inflammation, bone cancer and
      bone repair. 

PMID- 24670262
TI  - The role of narrative medicine in pregnancy after liver transplantation.
AB  - Narrative medicine allows professionals from all fields of medical sciences to
      understand the patient's total experience of illness, and meet his/her needs in
      an empathetic environment. Narrative medicine helps spread holistic knowledge of
      a multitude of complex clinical conditions, including transplantation. OBJECTIVE:
      To underline the role of narrative medicine in women who become pregnant after a
      liver transplant by using their narrations of this very special experience.
      METHODS: We describe our study with narration and listening to the stories of
      three women expecting their first child after a liver transplant, by analysing
      the structure and role of narration in the context of relationships between
      patients and caregivers. The narrations were transcribed verbatim with the main
      plot analysed in order to address all the aspects of this rare clinical condition
      and the transition to parenthood. RESULTS: The women narrated this experience in
      three phases: transplantation, pregnancy and delivery, and post-partum. They
      described all phases of pregnancy as stressful but satisfying, whereas the fact
      of becoming a mother was perceived as a victory both as a woman and as a
      transplant patient. CONCLUSIONS: Our results suggest that narrative medicine
      represents a significant professional tool for caring for transplant patients
      during pregnancy.

PMID- 24670263
TI  - The influence of relationship power dynamics on HIV testing in rural Malawi.
AB  - Using the theory of gender and power (TGP) and data from the Tsogolo la Thanzi
      (TLT) study, we examined how relationship power shapes young people's decisions
      to test for HIV in rural Malawi (N=932), a high-HIV prevalence setting undergoing
      rapid expansions in testing services. We used generalized estimating equations
      (GEE) to examine associations among five constructs of relationship power
      (socioeconomic inequalities, relationship dominance, relationship violence,
      relationship unity, and mistrust), perceived risk, and receiving an HIV test over
      a 16-month period. The results indicate that young Malawians are testing for HIV
      at relatively high rates, repeatedly, and not just during pregnancy. Over the
      study period, 47.3% of respondents received at least one HIV test outside of TLT
      (range: 0-4). The GEE analysis revealed that men and women with higher levels of
      relationship unity were less likely to test for HIV. For men, being a victim of
      sexual coercion was an additional barrier to testing. Women's testing decisions
      were more strongly influenced by perceptions of a partner's risk for HIV than
      their own, whereas men relied more on self-assessments. The results highlight
      that testing decisions are deeply embedded within the relationship context, which
      should be considered in future HIV testing interventions. 

PMID- 24670264
TI  - Cloning and expression of progesterone receptor isoforms A and B in bovine corpus
      luteum.
AB  - Progesterone (P4) affects a cell through its nuclear receptor (PGR), which has
      two main isoforms: A (PGRA) and B (PGRB). A partial section of previously unknown
      PGRB cDNA from cattle was cloned. Next, mRNA and protein levels for these two
      isoforms in corpora lutea (CL) collected during different stages of the oestrous
      cycle and pregnancy were determined. The PGRB mRNA level was highest on Days 2-5
      of the oestrous cycle, decreased over the next few days (P<0.01) and increased
      again slightly on Days 17-20 (P<0.05). During pregnancy, PGRB mRNA was at its
      lowest level during Weeks 3-5 (P<0.01) and highest during Weeks 6-12 (P<0.01).
      The profile of PGRA mRNA levels was similar to that of PGRB throughout the
      oestrous cycle. The PGRA protein level was highest on Days 2-10 of the oestrous
      cycle, decreased continuously to its lowest concentration on Days 17-20 (P<0.01)
      and during Weeks 3-5 of pregnancy (P>0.05) and increased during Weeks 6-12
      (P<0.05). PGRB protein concentration followed a similar pattern but at a markedly
      lower level. Both PGRA and PGRB isoforms are involved in the regulation of P4
      action, especially in the newly formed CL and developed CL in the first trimester
      of pregnancy. These data suggest that the variable expression of these isoforms
      during the oestrous cycle may depend on the influence of P4. 

PMID- 24670266
TI  - Effects of eicosapentaenoic acid on the levels of inflammatory markers, cardiac
      function and long-term prognosis in chronic heart failure patients with
      dyslipidemia.
AB  - AIMS: The effects of eicosapentaenoic acid (EPA) on the levels of inflammatory
      markers, cardiac function and long-term prognosis in chronic heart failure (CHF)
      patients with dyslipidemia remain unclear. METHODS: A total of 139 CHF patients
      with a mean left ventricular ejection fraction (LVEF) of 37.6+/- 8.0% were
      divided into two groups based on whether EPA was included in their treatment
      regimen: the EPA group (n=71) and the no EPA group (n=68). Only patients with
      dyslipidemia at baseline (entry) were treated with EPA. The monocyte
      chemoattractant protein (MCP)-1 and asymmetric dimethylarginine (ADMA) levels
      were measured at baseline and after 12 months of treatment. RESULTS: At 12
      months, in the EPA group, the LVEF had improved and the MCP-1 and ADMA levels had
      decreased (respectively, p<0.001); however, in the no EPA group, the LVEF had
      worsened, while the MCP-1 and ADMA levels had increased (respectively, p<0.001).
      Fifty-five patients experienced cardiac events, including 15 cardiac deaths and
      40 readmissions for worsening of CHF during a median follow-up period of 28.0
      months. The percent change in LVEF from baseline was found to be significantly
      associated with the percent change in ADMA (r=-0.462, p<0.001). A multivariate
      Cox hazard analysis showed EPA treatment (hazard ratio: 0.21, 95% confidence
      interval: 0.05-0.93, p=0.031) to be an independent predictor of cardiac events.
      CONCLUSIONS: These data indicate that EPA treatment may improve the cardiac
      function and long-term prognosis of CHF patients with dyslipidemia, at least in
      part, due to reductions in inflammation and improvements in the endothelial
      function.

PMID- 24670265
TI  - Post-assembly functionalization of supramolecular nanostructures with bioactive
      peptides and fluorescent proteins by native chemical ligation.
AB  - Post-assembly functionalization of supramolecular nanostructures has the
      potential to expand the range of their applications. We report here the use of
      the chemoselective native chemical ligation (NCL) reaction to functionalize self
      assembled peptide amphiphile (PA) nanofibers. This strategy can be used to
      incorporate specific bioactivity on the nanofibers, and as a model, we
      demonstrate functionalization with the RGDS peptide following self-assembly.
      Incorporation of bioactivity is verified by the observation of characteristic
      changes in fibroblast morphology following NCL-mediated attachment of the signal
      to PA nanofibers. The NCL reaction does not alter the PA nanofiber morphology,
      and biotinylated RGDS peptide was found to be accessible on the nanofiber surface
      after ligation for binding with streptavidin-conjugated gold nanoparticles. In
      order to show that this strategy is not limited to short peptides, we utilized
      NCL to conjugate yellow fluorescent protein and/or cyan fluorescent protein to
      self-assembled PA nanofibers. Forster resonance energy transfer and fluorescence
      anisotropy measurements are consistent with the immobilization of the protein on
      the PA nanofibers. The change in electrophoretic mobility of the protein upon
      conjugation with PA molecules confirmed the formation of a covalent linkage. NCL
      mediated attachment of bioactive peptides and proteins to self-assembled PA
      nanofibers allows the independent control of self-assembly and bioactivity while
      retaining the biodegradable peptide structure of the PA molecule and thus can be
      useful in tailoring design of biomaterials. 

PMID- 24670267
TI  - Generation of rodent malaria parasites with a high mutation rate by destructing
      proofreading activity of DNA polymerase delta.
AB  - Plasmodium falciparum malaria imposes a serious public health concern throughout
      the tropics. Although genetic tools are principally important to fully
      investigate malaria parasites, currently available forward and reverse tools are
      fairly limited. It is expected that parasites with a high mutation rate can
      readily acquire novel phenotypes/traits; however, they remain an untapped tool
      for malaria biology. Here, we generated a mutator malaria parasite (hereinafter
      called a 'malaria mutator'), using site-directed mutagenesis and gene
      transfection techniques. A mutator Plasmodium berghei line with a defective
      proofreading 3' -> 5' exonuclease activity in DNA polymerase delta (referred to
      as PbMut) and a control P. berghei line with wild-type DNA polymerase delta
      (referred to as PbCtl) were maintained by weekly passage in ddY mice for 122
      weeks. High-throughput genome sequencing analysis revealed that two PbMut lines
      had 175-178 mutations and a 86- to 90-fold higher mutation rate than that of a
      PbCtl line. PbMut, PbCtl, and their parent strain, PbWT, showed similar course of
      infection. Interestingly, PbMut lost the ability to form gametocytes during
      serial passages. We believe that the malaria mutator system could provide a novel
      and useful tool to investigate malaria biology. 

PMID- 24670268
TI  - Human adult bone marrow-derived stem cells decrease severity of
      lipopolysaccharide-induced acute respiratory distress syndrome in sheep.
AB  - INTRODUCTION: Acute respiratory distress syndrome (ARDS) is the most common cause
      of respiratory failure among critically ill subjects, sepsis and severe bacterial
      pneumonia being its most common causes. The only interventions that have proven
      beneficial are protective ventilation strategies and fluid conservation
      approaches. New therapies are needed to address this common clinical problem.
      Others and we have previously shown the beneficial effect of infusion of
      exogenous adult stem cells in different pre-clinical models of ARDS. METHODS: In
      the present study endotoxin was infused intravenously into 14 sheep from which 6
      received different doses of adult stem cells by intrabronchial delivery to
      evaluate the effect of stem cell therapy. RESULTS: After administration of
      endotoxin, there was a rapid decline in oxygenation to hypoxemic values,
      indicative of severe-to-moderate ARDS. None of the animals treated with saline
      solution recovered to normal baseline values during the 6 hours that the animals
      were followed. In contrast, sheep treated with a dose of 40 million adult stem
      cells returned their levels of oxygen in their blood to baseline two hours after
      the cells were infused. Similarly, improvements in carbon dioxide (CO2)
      clearance, pulmonary vascular pressures and inflammation were observed and
      confirmed by histology and by the decrease in lung edema. CONCLUSIONS: We
      concluded that instillation of adult non-hematopoietic stem cells can diminish
      the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and
      inflammation in the ovine model, making the use of adult stem cells a real
      alternative for future therapies for ARDS.

PMID- 24670269
TI  - Adults in the income range for the Affordable Care Act's Medicaid expansion are
      healthier than pre-ACA enrollees.
AB  - The Affordable Care Act (ACA) has dramatically increased the number of low-income
      nonelderly adults eligible for Medicaid. Starting in 2014, states can elect to
      cover individuals and families with modified adjusted gross incomes below a
      threshold of 133 percent of federal poverty guidelines, with a 5 percent income
      disregard. We used simulation methods and data from the Medical Expenditure Panel
      Survey to compare nondisabled adults enrolled in Medicaid prior to the ACA with
      two other groups: adults who were eligible for Medicaid but not enrolled in it,
      and adults who were in the income range for the ACA's Medicaid expansion and thus
      newly eligible for coverage. Although differences in health across the groups
      were not large, both the newly eligible and those eligible before the ACA but not
      enrolled were healthier on several measures than pre-ACA enrollees. Twenty-five
      states have opted not to use the ACA to expand Medicaid eligibility. If these
      states reverse their decisions, their Medicaid programs might not enroll a
      population that is sicker than their pre-ACA enrollees. By expanding Medicaid
      eligibility, states could provide coverage to millions of healthier adults as
      well as to millions who have chronic conditions and who need care.

PMID- 24670270
TI  - Quantifying the uncertainty in heritability.
AB  - The use of mixed models to determine narrow-sense heritability and related
      quantities such as SNP heritability has received much recent attention. Less
      attention has been paid to the inherent variability in these estimates. One
      approach for quantifying variability in estimates of heritability is a
      frequentist approach, in which heritability is estimated using maximum likelihood
      and its variance is quantified through an asymptotic normal approximation. An
      alternative approach is to quantify the uncertainty in heritability through its
      Bayesian posterior distribution. In this paper, we develop the latter approach,
      make it computationally efficient and compare it to the frequentist approach. We
      show theoretically that, for a sufficiently large sample size and intermediate
      values of heritability, the two approaches provide similar results. Using the
      Atherosclerosis Risk in Communities cohort, we show empirically that the two
      approaches can give different results and that the variance/uncertainty can
      remain large.

PMID- 24670272
TI  - Intraosseous vascularization of anterior mandible: a radiographic analysis.
AB  - The anterior mandible was initially considered a safe zone from a surgical point
      of view. Over time, serious complications resulting from dental implantology
      procedures have been reported. This has led to a greater focus on vascularization
      of the interforaminal region. The purpose of this article was to evaluate the
      anterior mandibular region in relation to the presence of canals perforating the
      buccal and lingual cortical plates. DICOM (Digital Imaging and Communications in
      Medicine) files of 100 cone beam computed tomography scans were analyzed by
      imaging software. All radiographic cross-sections between the mental foramina
      were examined to detect the presence and location of perforating buccal or
      lingual canals. Lingual perforating canals are present in 98% of the cohort. The
      most common site is the symphysis region. The presence of 2 lingual canals
      cranially and caudally to the genial apophysis has been found in 39%. Vestibular
      perforating canals are absent in 61%. The anterior mandible has several lingual
      perforating canals, which are variable in number and location. Imaging software
      is a valuable aid in presurgical planning. Because of the higher prevalence of
      perforating canals in the symphysis region, this site should be preserved.

PMID- 24670271
TI  - Association study of common polymorphisms in MSRA, TFAP2B, MC4R, NRXN3, PPARGC1A,
      TMEM18, SEC16B, HOXB5 and OLFM4 genes with obesity-related traits among
      Portuguese children.
AB  - At least 52 genetic loci were associated with obesity-related traits. However,
      little is known about the genetic basis of obesity among children. This study
      aims to test whether 10 polymorphisms in obesity-related genes methionine
      sulfoxide reductase A (MSRA), transcription factor AP-2 beta (TFAP2B),
      melanocortin 4 receptor (MC4R), neurexin 3 (NRXN3), peroxisome proliferator
      activated receptor gamma coactivator 1 alpha (PPARGC1A), transmembrane protein 18
      (TMEM18), homolog of S. cerevisiae Sec16 (SEC16B), homeobox B5 (HOXB5) and
      olfactomedin 4 (OLFM4) are associated with the risk of obesity in Portuguese
      children. A total of 730 children aging from 6 to 12 years old, recruited
      randomly from public schools in Portugal, were analysed. Anthropometric
      measurements were obtained and children were classified into three phenotypic
      groups, normal weight (n=256), overweight (n=320) and obese (n=154), according to
      the International Obesity Task Force cutoffs. Polymorphisms were genotyped by
      allelic discrimination TaqMan assays. The MC4R rs12970134 polymorphism was
      nominally associated with body mass index (BMI) (P=0.035), BMI Z-score (P=0.043)
      and waist circumference (P=0.020), and borderline associated with weight
      (P=0.053). Near nominal associations were also found for the PPARGC1A rs8192678
      polymorphism with weight (P=0.061), and for the MSRA rs545854 polymorphism with
      BMI (P=0.055) and BMI Z-score (P=0.056). Furthermore, logistic regression showed
      that MC4R rs12970134 and TFAP2B rs987237 were nominally, respectively, associated
      (P=0.029) and borderline associated (P=0.056) with the obese phenotype. This
      study highlighted the possible association of MC4R, PPARGC1A, MSRA and TFAP2B
      polymorphisms with several obesity-related traits in a sample of Portuguese
      children. The two significant associated TFAP2B rs987237 and MC4R rs12970134
      polymorphisms showed an opposite direction of effect to that in the original
      reports. 

PMID- 24670273
TI  - Silicone intubation for nasolacrimal duct stenosis in adults: monocanalicular or
      bicanalicular intubation.
AB  - PURPOSE: The purpose of this study was to compare the success rate of
      monocanalicular versus that of bicanalicular silicone intubations of the
      nasolacrimal duct for nasolacrimal duct stenosis (NLDS) in adults (patent
      nasolacrimal duct with resistance to positive-pressure irrigation). MATERIALS AND
      METHODS: In a prospective randomized clinical trial, 52 eyes of 38 patients with
      NLDS underwent either monocanalicular silicone intubation (MCI) (n = 26 eyes) or
      bicanalicular silicon intubation (BCI) (n = 26 eyes). All procedures were
      performed by 1 oculoplastic surgeon. Tube removal was planned for 3 months
      postoperatively. Treatment success was defined as the complete resolution of
      epiphora or intermittent epiphora with normal dye disappearance test at 6 months
      after tube removal. RESULTS: The surgical outcome was assessed in 25 eyes with
      MCI and 21 eyes with BCI. The mean (SD) age of treatment was 52.7 (18.6) years
      for MCI and 49 (18.8) years for BCI. Treatment success was achieved in 19 of 25
      eyes (76%) in the MCI group compared with 16 of 21 eyes (76.2%) in the BCI group.
      Differences between the 2 groups proved to be not significant (P = 0.9). The only
      complication was peripunctal pyogenic granuloma in 2 eyes with BCI. CONCLUSIONS:
      Both MCI and BCI were successful in a similar percentage of patients with NLDS.
      The main advantages of the former technique were simple insertion and easy
      removal of the tube.

PMID- 24670274
TI  - Idiopathic orbital myositis.
AB  - PURPOSE: There is a paucity of reliable data and limited experience on the
      clinical features and therapeutic outcomes of orbital myositis. The purpose of
      this study was to collate data on the clinical features, imaging, diagnosis, and
      therapeutic effects of case reports from patients with myositis of idiopathic
      orbital inflammation pseudotumor in a tertiary eye hospital in China. METHODS: A
      retrospective study was performed on the records of 44 Chinese patients with
      orbital myositis. Data were obtained from the period of January 1, 2000, to
      August 31, 2010, from patients treated at the Eye Hospital of the Zhongshan
      Ophthalmic Center at Sun Yat-sen University, Guangzhou, China. RESULTS: Twenty
      five patients were women and 19 men. The mean age was 39.1 years (range, 11-77
      years). Right eyes were involved in 18 cases, left in 17 cases, and both eyes in
      9 cases. Dysfunctions of the affected muscles included pure paretic (20.5%), pure
      restrictive (45.5%), or mixed paretic-restrictive (34.1%). The ratio of acute to
      subacute stage was 1:3. The rank order of affected muscles was as follows:
      superior rectus (29.1%), lateral rectus (25.6%), medial rectus (24.4%), inferior
      rectus (19.8%), and superior oblique (1.16%). The proportion of single muscle
      involvement was 37.5%, and tendon involvement was seen in 40.9% of the muscles.
      All patients were treated with systemic corticosteroids (prednisone or
      dexamethasone). Full recovery was achieved in 38.6% of patients, whereas 59.1%
      achieved partial recovery with an average of 6.4 recurrences (range, 2.0-8.0
      recurrences). Recurrences occurred in 81.8% of the patients. CONCLUSIONS: Orbital
      myositis occurs in multiple clinical manifestations and may be recurrent. Imaging
      is an important technique for use in diagnosis. Systemic corticosteroid
      represents an effective approach for treatment.

PMID- 24670275
TI  - Use of distraction osteogenesis in arrhinia.
AB  - Nasal malformations such as hemiarrhinia and arrhinia have a very low incidence,
      although many treatment protocols have been described. In this article, we
      describe 2 surgical techniques to treat arrhinia depending on the age at the
      beginning of treatment. In our practice, we use Le Fort III osteotomy with
      distraction osteogenesis as a pillar of the reconstruction because it allows to
      improve anteroposterior and vertical projections of the midface, giving a proper
      platform for nasal reconstruction, decreasing the number of interventions. We
      report a patient with a hemiarrhinia who has completed appropriate reconstruction
      results and a patient with total arrhinia in whom the distraction was achieved to
      create a nasal bone support and improve midface projection. 

PMID- 24670276
TI  - Mandibular reconstruction with a prefabricated free vascularized fibula and
      implant-supported prosthesis based on fully three-dimensional virtual planning.
AB  - Because optimal reconstruction of maxillofacial defects requires functional
      rehabilitation, the current study demonstrates the successful secondary
      reconstruction of a large mandibular continuity defect using a fully digitally
      planned prefabricated free vascularized fibula with immediate implant-supported
      prosthodontic restoration. A 56-year-old man presented with a large mandibular
      continuity defect after resection of an enlarged squamous cell carcinoma arising
      from the floor of the mouth. For secondary reconstruction, the shape of the
      neomandible and implant position for support of the lower prosthesis were planned
      virtually. The combined cutting and drilling guide was printed in 3 dimensions.
      In a 2-step surgical approach, first, the implants were inserted into the fibula
      and covered with a split-thickness skin graft to form a neogingiva. In a second
      operation, the fibula was harvested, osteotomized, and fixed with the denture on
      the preinserted implants. The fibula was placed to its final position guided by
      the occlusion. Using three-dimensional virtual backward planning, it was feasible
      to perform a mandibular reconstruction with immediate prosthetic rehabilitation.

PMID- 24670277
TI  - Endoscopic surgery for recurrent undifferentiated nasopharyngeal carcinoma.
AB  - One of the biggest challenges for otolaryngologists is represented by the locally
      recurrent undifferentiated nasopharyngeal carcinoma (uNPC). Despite improvements
      in its treatment options, such as modern radiotherapy, chemotherapy, or external
      surgical approaches, the risk for severe complications, functional disabilities,
      and even death remains considerable. Over the years, advances in endoscopic
      surgery have led to a new alternative in the salvage surgery for recurrent uNPC:
      the nasopharyngeal endoscopic resection (NER). We retrospectively reviewed
      clinical records of 8 patients (6 men and 2 women), who underwent NER for
      recurrent T1 (rT1) locally recurrent uNPC between 2008 and 2011. Together with
      resections for subsequent recurrences, a total of 9 NERs were performed by a
      single surgeon with curative intent. Negative margins were obtained for the whole
      group of patients. After a mean follow-up period of 27 months (range, 16-54 mo),
      all the patients had no evidence of the disease. We had only 1 recurrence after 7
      months. Two-year overall survival and disease-free survival rates were 100% and
      88.9%, respectively. Only 1 patient presented with a complication, osteitis.
      Nasopharyngeal endoscopic resection can be considered a valid and promising
      treatment option for rT1 locally recurrent uNPC, showing encouraging short-term
      outcomes and complication rate. Long-term follow-up is needed to state the
      efficacy of NER, together with a larger number of patients. 

PMID- 24670278
TI  - Priorities for the education of members of the American Society of Maxillofacial
      Surgery.
AB  - We present the complete results of our 2013 survey of the members of the American
      Society of Maxillofacial Surgery (ASMS). We surveyed all 799 members of the
      Society from around the world regarding educational themes and modalities they
      wish to add to future ASMS educational programs. We also asked our members about
      surgical modalities and care paths in which they have the most expertise. The
      objective of the survey was to provide data that can be used to improve the
      education and training of the ASMS members. The results suggest that some widely
      taught topics perhaps should be taught less, whereas coverage of other topics
      should be increased.

PMID- 24670279
TI  - Histopathological characteristics of nasal polyps in smokers and non-smokers.
AB  - OBJECTIVE: It is known that cigarette smoking causes squamous metaplasia in upper
      and lower airways. We hypothesized that in patients with nasal polyposis, nasal
      polyps of smokers might reveal some histopathological changes and there might be
      an increased neoplasia risk. Therefore, in this study, we aimed to explore the
      effects of smoking on nasal polyp histopathology and clinical measures. STUDY
      DESIGN: Retrospective chart review. SETTING: Fatih Sultan Mehmet Education and
      Research Hospital. MATERIAL AND METHODS: Thirty smoker and 47 non-smoker patients
      with nasal polyposis who underwent endoscopic sinus surgery between 2007 and 2011
      were enrolled in this study to assess effect of smoking on histopathological
      characteristics of nasal polyps and clinical measures such as endoscopy score,
      computed tomography score of Lund-Mackay, Nasal Obstruction Symptom Evaluation
      (NOSE) Scale, presence of allergy and asthma, and blood eosinophil level.
      RESULTS: No statistically significant differences were found between smoker and
      non-smoker groups with regard to histopathological findings. Also, there were no
      significant correlation defined by endoscopy, computed tomography, and NOSE
      scores of patients between 2 groups. Smoking did not have a significant effect on
      the presence of allergy or asthma. But blood eosinophil levels were found to be
      significantly high in the smoker group. CONCLUSION: This is the first clinical
      study that investigates the effect of smoking on nasal polyp histopathology. In
      spite of the fact that smoking is associated with histopathological changes in
      respiratory mucosa, we did not find any significant change in histopathological
      characteristics of nasal polyps in smokers.

PMID- 24670280
TI  - Clinical outcomes of conjunctiva-Muller muscle resection: association with
      phenylephrine test-negative blepharoptosis and dry eye syndrome.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical outcomes of
      conjunctiva-Muller muscle resection (CMMR) in patients with mild to moderate
      ptosis, the factors related to successful procedures, and the influence of CMMR
      on dry eye symptoms and signs. METHODS: In a tertiary university hospital, the
      medical records of 30 patients who had CMMR were retrospectively reviewed,
      including the detailed preoperative and postoperative eyelid measurements,
      surgical outcomes, and dry eye evaluations. Inclusion criteria included older
      than 18 years, acquired ptosis, and no previous eyelid surgery or trauma.
      RESULTS: The surgery had a success rate of 86.7%. In the patients who responded
      to phenylephrine application with a marginal reflex distance 1 (MRD1) increase of
      more than 2 mm, the postoperative MRD1 correction was 2.41 +/- 0.84 mm, whereas
      the postoperative MRD1 correction was 1.19 +/- 0.78 mm in the group with
      responses of less than 2 mm. The postoperative MRD1 correction was 1.21 +/- 0.80
      mm in the group with a negative response. Seven patients complained of dry eye
      symptoms and showed a transiently significant aggravation in the Schirmer test
      and ocular surface disease index score after the procedure, which normalized
      within 2 months postoperatively. CONCLUSIONS: Responsiveness to phenylephrine is
      directly correlated with the postoperative results. Nevertheless, even in the
      patients with negative phenylephrine response, some degree of eyelid elevation
      can be expected. Damage to goblet cells after the procedure may result in
      defective tear production, leading to transient aggravation of dry eye symptoms.

PMID- 24670281
TI  - Evaluation of stability after orthognathic surgery with minimal orthodontic
      preparation: comparison according to 3 types of fixation.
AB  - This study was performed to evaluate the patterns and amount of postsurgical
      relapse after mandibular setback surgery with minimal orthodontic preparation. We
      also compared the stability of plate according to types. From January 2009 to
      February 2012, 26 patients (13 males, 13 females) at Seoul National University
      Bundang Hospital were identified. All patients underwent presurgical orthodontic
      treatment in less than 6 months and had mandibular setback surgery. Lateral
      cephalograms were taken presurgically (T0), immediately after surgery (T1), and 6
      months after surgery (T2). To evaluate surgical change and surgical relapse,
      linear and angular measurements were performed, and results were analyzed.
      Comparison of the vertical and horizontal relapses between groups (group 1:
      sliding plate, group 2: conventional metal plate, group 3: resorbable plate) was
      also performed. The overall mandibular relapse was 2.80 (SD, 3.86) mm (pogonion)
      and 3.85 (SD, 4.44) mm (menton) anteriorly, and 1.2 (SD, 3.39) (pogonion) and
      1.47 (SD, 3.48) mm (menton) superiorly. There was no significant difference among
      the 3 groups, however (P > 0.05). When mandibular setback surgery was performed,
      surgical relapse would occur anteriorly and superiorly. Significant difference
      can hardly be found among the 3 groups in terms of the amount of vertical and
      horizontal relapses. 

PMID- 24670282
TI  - Wavelet coherence analysis of prefrontal oxygenation signals in elderly subjects
      with hypertension.
AB  - This study aims to assess the prefrontal functional connectivity in elderly
      subjects with hypertension during the resting state using wavelet coherence
      analysis of changes in prefrontal tissue oxyhaemoglobin concentrations
      (Delta[HbO2]) signals measured by near-infrared spectroscopy (NIRS). Continuous
      recordings of NIRS signals were obtained from the left and right prefrontal lobes
      in 24 elderly subjects with hypertension (age: 70.7 +/- 8.4 years) and 26 elderly
      normotensive subjects (age: 70.6 +/- 7.9 years) during the resting state. The
      coherence between the left and right prefrontal oscillations in four frequency
      intervals (I, 0.4 Hz to 2 Hz; II, 0.15 Hz to 0.4 Hz; III, 0.05 Hz to 0.15 Hz; and
      IV, 0.02 Hz to 0.05 Hz) was analyzed using wavelet coherence method. The
      Delta[HbO2] oscillations showed significant wavelet coherence (WCO) in intervals
      I and III, and significant wavelet phase coherence (WPCO) in intervals from I to
      IV. Remarkably, in elderly subjects with hypertension, the WCO and WPCO in
      interval III were significantly lower in the left and right prefrontal regions
      than in healthy elderly subjects (p = 0.014 for WCO, p = 0.007 for WPCO). The
      lower coherence in interval III indicates a decreased synchronization of neural
      control in the left and right prefrontal regions in elderly subjects with
      hypertension. This might suggest a weakened brain functional connectivity in the
      elderly subjects with hypertension. 

PMID- 24670283
TI  - Failure to change care provision will leave more UK trusts in financial
      difficulty, say MPs.

PMID- 24670284
TI  - Current world literature. Myeloid biology.

PMID- 24670286
TI  - The relationship between apathy and participation in therapeutic activities in
      nursing home residents with dementia: Evidence for an association and directions
      for further research.
AB  - Apathy is one of the most frequent and early symptoms of dementia. Because apathy
      is characterised by lack of initiative and motivation, it leads to considerable
      burden being placed on carers to ensure that the person living with dementia has
      a reasonable quality of life. The aim of this study was to investigate the
      relationship between apathy and participation in therapeutic activities for older
      people with dementia living in nursing homes. Ninety residents were recruited
      into the study, and apathy was measured by nursing home staff using the Apathy
      Evaluation Scale Clinician version. Staff also compiled data on each resident's
      involvement in therapeutic activities. Among this sample, the mean age was 84.8
      years, and mean length of stay in the nursing home was 1.8 years. The mean apathy
      score was 50.4, indicating that on average the residents had a moderate level of
      apathy. Overall, residents participated in six activities per week and those
      residents who were involved in the most activities had the lowest levels of
      apathy. This paper provides evidence that residents involved in therapeutic
      activities have lower levels of apathy. Further research should be conducted on
      the direction of causality, whether apathy levels can be changed through
      participation in therapeutic activities, the relationship between dementia
      severity and modifiability of apathy, and the intensity of therapeutic activities
      required to maintain functioning. 

PMID- 24670289
TI  - Reconceive shamanism related theory of schizophrenia.
AB  - In this review we try to summarize the concepts, hypotheses and facts about
      schizophrenia and shamanism. Because during this dispute the evolutionary
      approach has been cited lately we briefly discuss this point of view as well. To
      make a proper comparison first we discuss the main characteristic of the two
      concepts. After a hundred years of medical research, schizophrenia is a
      diagnostic term useful in clinical practice but ambiguously defined
      scientifically. In ethnology the term shamanism also cover a wide
      phenomenological spectrum, so we exclude the differences to stipulate the essence
      of shamanism in order to make the comparison with schizophrenia possible. Than we
      discuss the pros and cons data on phenomenological similarity, course and
      prognosis, epidemiology and available psychological items. We finally reach the
      same conclusion as the recent ethnological literature that in connection with
      shamanism schizophrenia should be avoided. However we consider the possible
      compromising explanations as well. 

PMID- 24670290
TI  - [The role of shame in development of the mental disorders I. Theoretical
      background].
AB  - Shame is a particularly intense, often incapacitating negative emotion involving
      feeling of inferiority, powerlessness and self-consciousness, along with the
      desire to hide or disappear. The experience of shame is an adaptive and natural
      reaction until it becomes a chronic and painful emotion as a result of
      environment and temperamental factors. According to studies of the last decade
      chronic shame is a central feature of the social interactions as well as of a
      variety of psychopathologies including anxiety disorders, depression, eating
      disorders, and personality disorders. This study presents an overview of the
      definition and the major theories of shame describing developmental factors of
      shame and ways to coping with it. The research results concerning the
      relationship between shame and different disorders will be summarized in a
      following study.

PMID- 24670287
TI  - Notch signaling genes: myogenic DNA hypomethylation and 5-hydroxymethylcytosine.
AB  - Notch intercellular signaling is critical for diverse developmental pathways and
      for homeostasis in various types of stem cells and progenitor cells. Because
      Notch gene products need to be precisely regulated spatially and temporally,
      epigenetics is likely to help control expression of Notch signaling genes.
      Reduced representation bisulfite sequencing (RRBS) indicated significant
      hypomethylation in myoblasts, myotubes, and skeletal muscle vs. many nonmuscle
      samples at intragenic or intergenic regions of the following Notch receptor or
      ligand genes: NOTCH1, NOTCH2, JAG2, and DLL1. An enzymatic assay of sites in or
      near these genes revealed unusually high enrichment of 5-hydroxymethylcytosine
      (up to 81%) in skeletal muscle, heart, and cerebellum. Epigenetics studies and
      gene expression profiles suggest that hypomethylation and/or hydroxymethylation
      help control expression of these genes in heart, brain, myoblasts, myotubes, and
      within skeletal muscle myofibers. Such regulation could promote cell renewal,
      cell maintenance, homeostasis, and a poised state for repair of tissue damage. 

PMID- 24670291
TI  - [Psychosis and violence -- literature review from a preventive point of view].
AB  - Clinical experience shows that being diagnosed with a serious mental illness
      (SMI) significantly increases the risk of violent behaviour. The study gives a
      brief overview of literature on the neurophysiological, cognitive and emotional
      factors hypothesized behind the violent behaviour of psychotic patients. Clinical
      profiles show that a distinct constellation of psychotic symptoms known as
      threat/control-override, comorbid substance abuse, decreased adherence to and
      compliance with treatment as well as a higher level of hostility as measured by
      the PANSS, are characteristic for these patients. There is, however, no
      established causal link between being diagnosed with SMI and committing a violent
      crime. In a great number of cases, the factors behind such a crime are not
      psychosis-related. The study postulates several pathways ending in violent
      behaviour that result from the interaction of multiple factors. Following a
      preventive approach, it focuses on preexisting factors that go unnoticed for many
      years before the appearance of violent behaviour and may therefore have
      significant predictive value. Elevated levels of catecholamines, the dysfunction
      of the ventromedial-orbitofrontal cortical-amygdala system, decreased grey matter
      volume in the hippocampal and parahippocampal areas have proven to be important
      markers of vulnerability. In many cases, these factors later show in distinct
      impairments of neurocognitive performance and emotional functioning, prominently
      indeficits of executive functioning as well as in increased levels of
      impulsivity. Based on these established premorbid markers, the study emphasizes
      the importance of the prevention of violent behaviour through the early detection
      of cognitive and emotional dysfunction and the application of corrective
      measures. 

PMID- 24670292
TI  - [Impulsivity - aggression - depression: study of adolescents' problem behavior in
      light of their personality traits].
AB  - BACKGROUND AND AIMS OF THE STUDY: Impulsivity is a personality trait that may
      determine our everyday living, quality of life, decisions. Impulsivity in
      particular has a great significance during adolescence as a part of the
      adolescent neuroanatomical and neuropsychiatric developmental processes. The main
      goal of the present study was to examine correlations among depressive
      symptomatology, types of aggressive behaviors (verbal, physical, psychic),
      impulsivity and other personality traits (risk-taking, empathy and self-efficacy)
      in adolescents. METHOD: Data collection was going on in Debrecen during the first
      semester of the year 2012 using classes from three high schools (N = 413), 237
      (57,4%) boys and 176 (42,6%) girls. The self-administered questionnaire contained
      items on mental health and personality traits beyond sociodemographics. After
      descriptive statistics, correlation and multiple linear regression analyses were
      applied to detect correlations. RESULTS: Girls reported more depressive symptoms
      and their level of empathy was also higher. In terms of aggression, significant
      gender difference was detected only in case of physical aggression with a surplus
      of boys. Based on multiple regression analyses, we may conclude that impulsivity
      acted as a risk factor both for mean levels of depressive symptomatology and
      aggression scales. Besides, lack of empathy proved to be related to physical
      aggression. In both sexes, self-efficacy was positively associated with verbal
      and physical aggression. Among girls, self-efficacy was a negative predictor of
      psychic aggression, that is, it seems to act as a protective factor. CONCLUSION:
      In summary, we may conclude that there are strong correlations among depressive
      symptomatology, aggressive behaviors and impulsivity, and this association may be
      colored by further personality traits, such as risk-taking, empathy, and self
      efficacy. There is a need for learning some basic effective techniques for
      aggression management and self control as early as adolescence.

PMID- 24670293
TI  - [The concept, the symptoms and the etiological factors of codependency].
AB  - The concept of codependency stems from the field of chemical dependency.
      Initially, codependent individuals meant women who dominated their partners and
      took care of them, while women actually were dependent upon their husbands.
      Nowadays, it has been recognized that men can become codependent as well, and its
      presence is not limited only to the relationship. This paper reviews the various
      interpretations of codependency and the empirical researches on the etiological
      factors of codependency. The explanatory models of codependency can be placed on
      a continuum of severity: psychopathology on the level of personality disorder,
      behavioural addiction, or excessive feminine behaviour. The etiology is
      mutifactorical: biological, psychological and social elements are also listed
      among etiology factors. The individual variability of the predisposition to care,
      failure of prefrontal cortex to inhibit empathic responses, a multitude of
      aversive experiences in a dysfunctional family (e.g. parental conflicts,
      emotional abuse, neglect and parentification), changes in the perception of
      women's role, and the emergence of substance abuse in the family could play a
      role in the development of codependency. Codependency is often unrecognized.
      Codependent individuals visit the health care system with stress-related or
      depressive symptoms which can mask the underlying causes, thus, it is possible
      that they will only receive symptomatic treatment. Through its trans-generational
      nature, codependency endangers children growing up in the family. 

PMID- 24670294
TI  - [Forensic psychiatric care -- the German model. Part 1: legal background and
      therapeutic practice].

PMID- 24670295
TI  - [Psychiatry, forensic psychiatry and society].

PMID- 24670296
TI  - [On the communicative approach of psychiatry -- autonomous identity, complexity,
      competencies].

PMID- 24670297
TI  - Sex hormone associations with breast cancer risk and the mediation of randomized
      trial postmenopausal hormone therapy effects.
AB  - INTRODUCTION: Paradoxically, a breast cancer risk reduction with conjugated
      equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone
      acetate (CEE + MPA) were observed in the Women's Health Initiative (WHI)
      randomized controlled trials. The effects of hormone therapy on serum sex hormone
      levels, and on the association between baseline sex hormones and disease risk,
      may help explain these divergent breast cancer findings. METHODS: Serum sex
      hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA
      trial and for 235 cases in the CEE trial along with corresponding pair-matched
      controls, nested within the WHI trials of healthy postmenopausal women.
      Association and mediation analyses, to examine the extent to which sex hormone
      levels and changes can explain the breast cancer findings, were conducted using
      logistic regression. RESULTS: Following CEE treatment, breast cancer risk was
      associated with higher concentrations of baseline serum estrogens, and with lower
      concentrations of sex hormone binding globulin. However, following CEE + MPA,
      there was no association of breast cancer risk with baseline sex hormone levels.
      The sex hormone changes from baseline to year 1 provided an explanation for much
      of the reduced breast cancer risk with CEE. Specifically, the treatment odds
      ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41,
      2.09) when the year 1 measures were included in the logistic regression analysis.
      In comparison, the CEE + MPA odds ratio was essentially unchanged when these year
      1 measures were included. CONCLUSIONS: Breast cancer risk remains low following
      CEE use among women having favorable baseline sex hormone profiles, but CEE + MPA
      evidently produces a breast cancer risk for all women similar to that for women
      having an unfavorable baseline sex hormone profile. These patterns could reflect
      breast ductal epithelial cell stimulation by CEE + MPA that is substantially
      avoided with CEE, in conjunction with relatively more favorable effects of either
      regimen following a sustained period of estrogen deprivation. These findings may
      have implications for other hormone therapy formulations and routes of delivery.
      TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00000611.

PMID- 24670298
TI  - Unique effects of mycophenolate mofetil on cord blood T cells: implications for
      GVHD prophylaxis.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a common treatment
      for hematological diseases. Cord blood (CB) is increasingly used as a source of
      stem cells for HSCT. Prophylactic drugs, such as mycophenolate mofetil (MMF) and
      cyclosporine A (CsA), are often used together after HSCT to prevent graft-versus
      host disease (GvHD), but so far little is known about their effects on CB
      mononuclear cells (CBMCs). As CB and peripheral blood (PB) have different cell
      compositions and characteristics, it was hypothesized that MMF and CsA might have
      different effects on CB and PB T cells. METHODS: Using a combination of flow
      cytometry, ELISA, and quantitative PCR, the effects of MMF, CsA, and the
      combination of both drugs were studied on resting and activated CBMCs and
      peripheral blood mononuclear cells. RESULTS: MMF had a stronger effect on
      activated PB T cells than on activated CB T cells, which was consistent with the
      lower level of IMPDH2 mRNA expressed by PB T cells. Interestingly, only MMF could
      preserve the activated CB regulatory T-cell population. Activated CB T cells were
      more sensitive to CsA than activated PB T cells, which might be explained by the
      lower NFATc1 expression and cytokine secretion. These results may explain the
      lower GvHD incidence observed in recipients of CB transplants. CONCLUSION: This
      study provides valuable insight into the effects of immunosuppressive drugs used
      after HSCT on resting and activated T-cell subsets from PB but especially from
      CB.

PMID- 24670299
TI  - T-cell-depleting antibodies and risk of cancer after transplantation.

PMID- 24670300
TI  - Hepatitis B in men who have sex with men and HIV-infected individuals: missed
      opportunities and future challenges.

PMID- 24670301
TI  - Validity of the Premature Ejaculation Diagnostic Tool in four subgroups of
      premature ejaculation syndrome: data from the Korean Internet Sexuality Survey -
      part 1.
AB  - Background The premature ejaculation diagnostic tool (PEDT) is a brief,
      multidimensional validated instrument devised for diagnosing premature
      ejaculation (PE). However, there is insufficient evidence regarding its ability
      to differentiate subgroups of PE. We assessed the ability of the PEDT to
      differentiate four subgroups of PE (lifelong, acquired, variable and subjective
      PE). METHODS: An internet-based survey was conducted with a population-based
      sample of males aged 20-59 years. Participants were asked to complete a
      questionnaire requesting detailed medical and sexual histories. The questionnaire
      including questions from the PEDT and from the Medical Outcome Study Short-form
      36-Item Health Survey (SF-36). Using the PEDT, PE was defined as a cutoff score
      of >=11. RESULTS: In this study, 443 subjects (mean age 39.3+/-10.1 years) were
      included. PEDT-PE prevalence was 14.6%. The proportions of PE subgroups and their
      mean PEDT scores were: lifelong PE, 2.9% and 15.5; acquired PE, 7.0% and 11.2;
      variable PE, 7.4% and 10.4; subjective PE, 3.2% and 9.0. PEDT scores were
      significantly higher in the lifelong PE group than in other the subgroups of PE
      (P<0.001). The subjective PE group had the lowest PEDT score, and their physical
      and mental component scores for the SF-36 were similar to those of non-PE
      subjects. CONCLUSIONS: This population-based cross-sectional survey has
      demonstrated that the PEDT is not appropriate for research into four subgroups of
      PE when used in an general male population study, unless the PEDT is combined
      with an additional questionnaire with specific questions on the four PE
      subgroups.

PMID- 24670302
TI  - Rapid HIV testing increases the rate of HIV detection in men who have sex with
      men: using rapid HIV testing in a primary care clinic.
AB  - Rapid HIV testing was approved in Australia in December 2012. Data was collected
      to describe the early experience of using rapid testing in Australia but as the
      information was collected, the authors noted that there appeared to be a high
      rate of HIV diagnoses amongst rapid testers. Further analysis confirmed this
      impression, when the rate was compared to a baseline rate of HIV diagnoses over
      the 32 months before the rapid testing started (4.1% vs 1.3%). 

PMID- 24670303
TI  - Sexual health, vulnerabilities and risk behaviours among homeless adults.
AB  - It is well known that homeless individuals are at risk for a variety of health
      problems, including sexually transmissible infections. Optimisation of health
      services for the homeless requires knowledge of their sexual health. The sexual
      health and sexual vulnerability factors of 500 homeless adults (196 women) were
      assessed in a cross-sectional survey in three Canadian cities. Our data indicate
      that a significant proportion of individuals and more women than men reported
      multiple experiences that compromise their sexual health exponentially. These
      findings may inform health policies related to sexuality to foster positive
      sexual health outcomes for all people, including marginalised populations. 

PMID- 24670308
TI  - "Reverse" bypass using a naturally formed "bonnet" superficial temporal artery in
      symptomatic common carotid artery occlusion: a case report.
AB  - We herein describe a patient with symptomatic common carotid artery occlusion who
      underwent a reverse superficial temporal artery (STA)-middle cerebral artery
      (MCA) single bypass using a naturally formed "bonnet" STA. The surgical procedure
      was performed without difficulty, and no further neurological deterioration was
      observed after surgery. In practice, this case highlights that the reverse STA
      MCA bypass can be achieved safely and less invasively using a naturally formed
      "bonnet" STA. 

PMID- 24670307
TI  - Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3
      affects ovarian response to FSH.
AB  - Genes critical for fertility are highly conserved in mammals. Interspecies DNA
      sequence variation, resulting in amino acid substitutions and post
      transcriptional modifications, including alternative splicing, are a result of
      evolution and speciation. The mammalian follicle-stimulating hormone receptor
      (FSHR) gene encodes distinct species-specific forms by alternative splicing.
      Skipping of exon 2 of the human FSHR was reported in women of North American
      origin and correlated with low response to ovarian stimulation with exogenous
      follicle-stimulating hormone (FSH). To determine whether this variant correlated
      with low response in women of different genetic backgrounds, we performed a
      blinded retrospective observational study in a Turkish cohort. Ovarian response
      was determined as low, intermediate or high according to retrieved oocyte numbers
      after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus
      cells collected from 96 women undergoing IVF/ICSI following controlled ovarian
      hyperstimulation revealed four alternatively spliced FSHR products in seven
      patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion
      in one patient each, and a retention of an intron 1 fragment in one patient. In
      all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3
      were exclusive to low responders and was independent of the use of agonist or
      antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of
      domestic cats--a good comparative model for human fertility. We tested the
      signaling potential of human and cat variants after transfection in HEK293 cells
      and FSH stimulation. None of the splicing variants initiated cAMP signaling
      despite high FSH doses, unlike full-length proteins. These data substantiate the
      occurrence of FSHR exon skipping in a subgroup of low responders and suggest that
      species-specific regulation of FSHR splicing plays diverse roles in mammalian
      ovarian function.

PMID- 24670306
TI  - Vaccination strategies for Parkinson disease: induction of a swift attack or
      raising tolerance?
AB  - Parkinson disease is the second most common neurodegenerative disease in the
      world, but there is currently no available cure for it. Current treatments only
      alleviate some of the symptoms for a few years, but they become ineffective in
      the long run and do not stop the disease. Therefore it is of outmost importance
      to develop therapeutic strategies that can prevent, stop, or cure Parkinson
      disease. A very promising target for these therapies is the peripheral immune
      system due to its probable involvement in the disease and its potential as a tool
      to modulate neuroinflammation. But for such strategies to be successful, we need
      to understand the particular state of the peripheral immune system during
      Parkinson disease in order to avoid its weaknesses. In this review we examine the
      available data regarding how dopamine regulates the peripheral immune system and
      how this regulation is affected in Parkinson disease; the specific cytokine
      profiles observed during disease progression and the alterations documented to
      date in patients' peripheral blood mononuclear cells. We also review the
      different strategies used in Parkinson disease animal models to modulate the
      adaptive immune response to salvage dopaminergic neurons from cell death. After
      analyzing the evidence, we hypothesize the need to prime the immune system to
      restore natural tolerance against alpha-synuclein in Parkinson disease, including
      at the same time B and T cells, so that T cells can reprogram microglia
      activation to a beneficial pattern and B cell/IgG can help neurons cope with the
      pathological forms of alpha-synuclein. 

PMID- 24670309
TI  - Venous reddening as a possible sign of hyperperfusion after superficial temporal
      artery-middle cerebral artery anastomosis for moyamoya disease: case report.
AB  - Here we report a case of moyamoya disease in which cortical veins reddened after
      superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis,
      following postoperative hyperperfusion. A 37-year-old man with moyamoya disease
      suffered cerebral infarction in his right hemisphere. Single photon emission
      computed tomography (SPECT) showed impaired cerebral blood flow (CBF) in both
      cerebral hemispheres. The patient underwent STA-MCA anastomosis in the right
      cerebral hemisphere. During operation, soon after declamping the STA, cortical
      veins near the anastomosis site changed its color from blue to red. This change
      was repeatable by clamping and declamping of the STA. Postoperative SPECT and
      computed tomography (CT) demonstrated increased CBF and subarachnoid hemorrhage
      at the anastomosis site, suggesting the occurrence of postoperative
      hyperperfusion. By strictly controlling the patient's blood pressure, the
      syndrome resolved 1 week after the operation. We propose that the venous
      reddening after STA-MCA anastomosis may be a sign of postoperative
      hyperperfusion. 

PMID- 24670310
TI  - Superficial siderosis of the central nervous system caused by hemorrhagic
      intraventricular craniopharyngioma: case report and literature review.
AB  - Superficial siderosis is a rare condition caused by hemosiderin deposits in the
      central nervous system (CNS) due to prolonged or recurrent low-grade bleeding
      into the cerebrospinal fluid (CSF). CNS tumor could be one of the sources of
      bleeding, both pre- and postoperatively. We report an extremely rare case of
      superficial siderosis associated with purely third ventricle craniopharyngioma,
      and review previously reported cases of superficial siderosis associated with CNS
      tumor. A 69-year-old man presented with headache, unsteady gait, blurred vision,
      and progressive hearing loss. Brain magnetic resonance (MR) imaging with
      gadolinium revealed a well enhanced, intraventricular mass in the anterior part
      of the third ventricle. T2*-weighted gradient echo (GE) MR imaging revealed a
      hypointense rim around the brain particularly marked within the depth of the
      sulci. Superficial siderosis was diagnosed based on these findings. The tumor was
      diffusely hypointense on T2*-weighted GE imaging, indicating intratumoral
      hemorrhage. The lateral ventricles were dilated, suggesting hydrocephalus.
      [(18)F]fluorodeoxyglucose positron emission tomography revealed increased uptake
      in the tumor. The whole brain surface appeared dark ocher at surgery.
      Histological examination showed the hemorrhagic tumor was papillary
      craniopharyngioma. His hearing loss progressed after removal of the tumor. T2*
      weighted GE MR imaging demonstrated not only superficial siderosis but also
      diffuse intratumoral hemorrhage in the tumor. Superficial siderosis and its
      related symptoms, including hearing loss, should be considered in patients with
      hemorrhagic tumor related to the CSF space. Purely third ventricle
      craniopharyngioma rarely has hemorrhagic character, which could cause superficial
      siderosis and progressive hearing loss. 

PMID- 24670311
TI  - Risk factors associated with cerebral vasospasm following aneurysmal subarachnoid
      hemorrhage.
AB  - We studied the risk factors associated with cerebral vasospasm following
      aneurysmal subarachnoid hemorrhage (SAH). The subjects were 370 patients with
      ruptured aneurysms who fulfilled all of the following criteria: admission by day
      2 after onset, operation performed by day 3 by the same surgeon (T.I.), Hunt-Hess
      grade I-IV, availability of bilateral carotid angiograms acquired by day 2 and
      repeated between days 7 and 9. The demographic, clinical, radiographic, surgical,
      laboratory, and electrocardiographic data were analyzed for angiographic
      vasospasm (AV), symptomatic vasospasm (SV), and cerebral infarction on computed
      tomography (CT) scan. Both CT-evident SAH and AV were graded as 0-IV. Among the
      370 patients, AV grade III-IV, SV, and cerebral infarction occurred in 26%, 24%,
      and 20%, respectively. Univariate analysis showed that Hunt-Hess grade III-IV,
      SAH grade III-IV, intracerebral or/and intraventricular hemorrhage, rebleeding,
      cigarette smoking, hypertension, alcohol intake, leukocytosis, hyperglycemia, and
      electrocardiographic QTc prolongation, left ventricular hypertrophy (LVH), and ST
      depression were significantly related to at least one of AV grade III-IV, SV, or
      cerebral infarction. Multivariate analysis showed that SAH grade III-IV was the
      most important risk factor for vasospasm followed by LVH on electrocardiogram,
      cigarette smoking, and hypertension. AV grade III-IV, SV, and cerebral infarction
      occurred in 57%, 54%, and 39% of the 46 smokers with LVH, and in 43%, 49%, and
      35% of the 68 patients who had both LVH and hypertension, respectively. CT
      evident SAH, LVH, cigarette smoking, and hypertension are associated with
      vasospasm. In smokers or hypertensive patients, premorbid LVH appears to predict
      much more severe vasospasm. 

PMID- 24670312
TI  - The safety and effectiveness of low-dose recombinant tissue plasminogen activator
      (0.6 mg/kg) therapy for elderly acute ischemic stroke patients (>= 80 years old)
      in the pre-endovascular era.
AB  - There are still few studies of low-dose recombinant tissue plasminogen activator
      (rtPA) therapy (0.6 mg/kg) for acute ischemic stroke (AIS) patients >= 80 years
      old, though most strokes occur in elderly people. The safety and effectiveness of
      this form of thrombolysis without endovascular therapy were evaluated in AIS
      patients >= 80 years old at our hospital. The data were collected from August
      2006 to April 2010, before approval of the Mechanical Embolus Removal in Cerebral
      Ischemia (MERCI) retriever in Japan. Intravenous rtPA was administered to
      patients within 3 hours of stroke onset. The incidence of intracerebral
      hemorrhage (ICH), the recanalization rate of the occluded artery, and the
      modified Rankin Scale (mRS) score 3 months after stroke were examined. The
      patients who received rtPA therapy were stratified into two age groups: a younger
      group (< 80 years) and an older group (>= 80 years). Of the 87 patients who
      received rtPA therapy, 17 (19.5%) were >= 80 years old. The incidence of
      symptomatic ICH was not significantly different between the younger (4.3%) and
      older (0%) groups (p = 0.61). The recanalization rate of the occluded artery was
      not significantly different between the younger (54%) and older (50%) groups (p =
      0.78). The rate of an mRS score of 0-2, 3 months after stroke was significantly
      higher in the younger (44.3%) than in the older group (11.8%) (p = 0.013). Low
      dose rtPA therapy appears to be as safe and feasible for AIS patients >= 80 years
      old as it is for younger people. This therapy should not be withheld because of
      age. 

PMID- 24670313
TI  - Evaluation of antibiotic-loaded calcium phosphate bone cement in an cranium
      infected experimental model.
AB  - Treatment of calvarial defects has remained a challenge in reconstruction
      surgery, especially because of infection at these sites. We produced a
      bactericidal biomaterial for treating infected bone defects by using calcium
      phosphate bone cement mixed with antibiotics. We evaluated the usefulness of this
      material mixed with the antibiotic vancomycin in a cranium-infected rat model.
      The concentration of vancomycin used was 5.0 wt%, as reported in our previous
      study. In order to establish the rat model, a cranium defect (diameter, 5 mm) was
      made that was infected with methicillin-resistant Staphylococcus aureus (MRSA).
      Thirty-six rats were divided into 6 groups depending on whether an autologous
      graft or bone cement with or without antibiotic was used for the defect. After 1
      and 4 weeks, abscess formation was checked, tissue bacterial counts were
      determined, and pathological examination was performed. At both 1 and 4 weeks, no
      MRSA was detected on tissue bacterial culture or pathological examination in
      groups that received bone cement with antibiotics. In groups that received bone
      cement without antibiotic, MRSA was detected, and the bone cement had compromised
      and disintegrated into several slices. In conclusion, bone cement that contains
      antibiotics appears to be effective not only for reconstruction in cases of
      cranial defect, but also in terms of preventing infection. 

PMID- 24670314
TI  - Novel neuromuscular electrical stimulation system for treatment of dysphagia
      after brain injury.
AB  - The purpose of this study was to compare the effects of a novel neuromuscular
      electrical stimulation (NMES) to the effects of conventional treatment in
      patients with dysphagia after brain injury. In total, 26 patients were non
      randomly divided into an experimental group (n = 12) and a control group (n =
      14). The experimental group received NMES intervention followed by conventional
      treatment, including thermaltactile stimulation with intensive repetition of a
      dry-swallow task. The control group received conventional treatment without NMES.
      NMES at a fixed pulse duration of 50 MUs and a frequency of 50 Hz was delivered
      over the skin areas above the motor point of the target muscles, i.e., the
      bilateral geniohyoid, mylohyoid/anterior belly of the digastric, and thyrohyoid
      muscles, using a high-voltage pulsed-current device. The two groups received 40
      min treatments once a day, 5 days per week, for 8 weeks. Outcome, assessed before
      and 8 weeks after treatment, was evaluated with regard to the videofluoroscopic
      dysphagia scale (VDS), the anterior and superior displacement of the hyoid bone
      and larynx, and the functional oral intake scale. Both groups exhibited
      improvement, but the experimental group exhibited more significant improvement in
      the displacement of the hyoid bone and larynx, VDS-total score, and VDS
      pharyngeal score than the control group did. The results suggest that NMES
      combined with conventional treatment is superior to conventional treatment alone
      in patients with dysphagia following treatment for brain injury. Further
      investigations are necessary to examine the effects of NMES in patients with more
      varied types of diseases. 

PMID- 24670315
TI  - A Novel Method for Super-selective Coil Embolization Using an Extremely Soft Bare
      Coil through a Liquid Embolic Delivery Microcatheter.
AB  - Endovascular coil embolization for intracranial aneurysms, arteriovenous
      malformations (AVMs), dural arteriovenous fistulas (AVFs), and hypervascular
      tumors are recognized as an effective adjunctive or curative treatment. In this
      setting, it is sometimes difficult to navigate a coil delivery microcatheter to
      the target point of a tiny, tortuous vessel. We herein present a case series of a
      novel method that enabled super-selective coil embolization using an extremely
      soft bare, electrodetachable coil (ED extrasoft((r)) coil) through a liquid
      embolic delivery microcatheter (Marathon((r))). The Marathon((r)) catheter was
      successfully placed at the target point of the tiny, tortuous vessel, and coil
      embolization was achieved in all 16 patients with 9 AVMs, 2 distal aneurysms, 2
      AVFs, and 3 meningiomas. The primary ED extrasoft((r)) coil and delivery wire
      have a very small radius, and the coil is rapidly detachable with an alarm notice
      from the generator even under Marathon((r)) with one marker. We believe that this
      technique can provide safe and efficient embolization for selected patients. 

PMID- 24670316
TI  - Blocking mimicry makes true and false smiles look the same.
AB  - Recent research suggests that facial mimicry underlies accurate interpretation of
      subtle facial expressions. In three experiments, we manipulated mimicry and
      tested its role in judgments of the genuineness of true and false smiles.
      Experiment 1 used facial EMG to show that a new mouthguard technique for blocking
      mimicry modifies both the amount and the time course of facial reactions. In
      Experiments 2 and 3, participants rated true and false smiles either while
      wearing mouthguards or when allowed to freely mimic the smiles with or without
      additional distraction, namely holding a squeeze ball or wearing a finger-cuff
      heart rate monitor. Results showed that blocking mimicry compromised the decoding
      of true and false smiles such that they were judged as equally genuine. Together
      the experiments highlight the role of facial mimicry in judging subtle meanings
      of facial expressions. 

PMID- 24670317
TI  - Angular and temperature dependence of current induced spin-orbit effective fields
      in Ta/CoFeB/MgO nanowires.
AB  - Current induced spin-orbit effective magnetic fields in metal/ferromagnet/oxide
      trilayers provide a new way to manipulate the magnetization, which is an
      alternative to the conventional current induced spin transfer torque arising from
      noncollinear magnetization. Ta/CoFeB/MgO structures are expected to be useful for
      non-volatile memories and logic devices due to its perpendicular anisotropy and
      large current induced spin-orbit effective fields. However many aspects such as
      the angular and temperature dependent phenomena of the effective fields are
      little understood. Here, we evaluate the angular and temperature dependence of
      the current-induced spin-orbit effective fields considering contributions from
      both the anomalous and planar Hall effects. The longitudinal and transverse
      components of effective fields are found to have strong angular dependence on the
      magnetization direction at 300 K. The transverse field decreases significantly
      with decreasing temperature, whereas the longitudinal field shows weaker
      temperature dependence. Our results reveal important features and provide an
      opportunity for a more comprehensive understanding of current induced spin-orbit
      effective fields.

PMID- 24670319
TI  - T follicular helper cells and HIV/SIV-specific antibody responses.
AB  - PURPOSE OF REVIEW: Here, we describe recent data on the characterization of
      follicular helper CD4 T cells (Tfh) and the dynamics of Tfh-B-cell interactions
      in HIV and simian immunodeficiency virus (SIV) infection and discuss important
      aspects of these interactions that need to be addressed in order to design more
      effective vaccines that elicit broadly neutralizing antibodies. RECENT FINDINGS:
      Mouse, nonhuman primate (NHP) and human Tfh cells share phenotypic, functional
      and molecular programs, which are regulated by local signals and spatiotemporal
      parameters. Chronic HIV/SIV infection results in accumulation of Tfh, germinal
      center B cells and circulating virus-specific immunoglobulins in some
      individuals. However, most HIV/SIV-infected individuals do not mount broadly
      neutralizing antibodies, pointing to functional defects in Tfh cells in chronic
      HIV/SIV infection. The susceptibility of particular CD4 T-cell populations to
      HIV/SIV infection within lymph nodes notably impacts upon the dynamics of Tfh
      germinal center B-cell interactions. Some circulating CD4 T cells share certain
      characteristics with Tfh cells, however, their direct origin from germinal center
      Tfh cells is not clear. SUMMARY: There are many ways in which HIV and SIV
      influence the complex signals and mechanisms regulating the development of Tfh
      cells and their interactions with germinal center B cells. Understanding the
      biology of Tfh cells will be necessary to appropriately recruit these cells
      during vaccination with the goal of stimulating a more broad and potent
      neutralizing antibody response.

PMID- 24670318
TI  - Epitope target structures of Fc-mediated effector function during HIV-1
      acquisition.
AB  - PURPOSE OF REVIEW: This review analyzes recent studies suggesting that highly
      conserved epitopes in the HIV-1 Env trimer are targets of potentially protective
      nonneutralizing antibodies that mediate antibody-dependent cellular cytotoxicity.
      RECENT FINDINGS: Recent studies in both non-human primates and humans suggest
      that nonneutralizing antibodies play a role in blocking infection with hybrid
      simian HIV (SHIV)/simian immunodeficiency virus (SIV) or HIV-1 by Fc-mediated
      effector function, in particular antibody-dependent cellular cytotoxicity.
      Further, several studies implicate highly conserved epitopes in the C1 region of
      gp120 as targets of these antibodies. However, these suggestions are
      controversial, as passive immunization studies do not indicate that such
      antibodies can block acquisition in non-human primates. Potential reasons for
      this discrepancy are discussed in the structural context of potent antibody
      dependent cellular cytotoxicity epitopes on target cells during the narrow window
      of opportunity when antibodies can block HIV-1 acquisition. SUMMARY: Cumulative
      evidence suggests that, in addition to virus neutralization, Fc-mediated effector
      responses to highly conserved epitopes in the HIV-1 trimer play distinct as well
      as overlapping roles in blocking HIV-1 acquisition. Evidence will be discussed as
      to whether nonneutralizing antibodies specific for epitopes on the HIV-1 Env
      trimer that become exposed during viral entry contribute significantly to
      blocking HIV-1 acquisition.

PMID- 24670320
TI  - The role of Fc receptors in HIV infection and vaccine efficacy.
AB  - PURPOSE OF REVIEW: In this review, the roles of Fc-gamma receptor polymorphisms
      are discussed in regards to HIV-1 vaccine efficacy, HIV acquisition, and disease
      progression. In addition, the significance of the neonatal immunoglobulin G (IgG)
      Fc receptor and potential effects of the aggregated immunoglobulin A Fc receptor
      (FcalphaR) are addressed. RECENT FINDINGS: Fc receptors undoubtedly play an
      important role in antibody-mediated action in HIV infection and vaccines. Several
      studies have determined an association between polymorphic variants of Fc-gamma
      RIIA and Fc-gamma-RIIIA in the acquisition and progression of HIV-1 infection,
      and in responses to vaccination regimens. A rather complex relationship exists
      between the relative affinity of these molecules and their impact on HIV disease
      acquisition and progression and HIV vaccine efficacy. SUMMARY: The discrepancies
      between different investigations of the role of Fc receptor polymorphisms appear
      to derive from the complex nature of the Fc receptor functions, including factors
      such as epistatic interactions and the race, sex, age, and relative risk behavior
      of the investigated individuals. Furthermore, Fc receptors in nonhuman primates
      (NHPs), the key model to study an AIDS-like disease in an animal model, appear to
      be even more diverse than in humans, and the function of these proteins has not
      been extensively explored. Given the critical role of Fc receptors in antibody
      mediated function in humans and NHP, more investigations are needed to fully
      understand and exploit these functions for vaccine design.

PMID- 24670322
TI  - Complement and the control of HIV infection: an evolving story.
AB  - PURPOSE OF REVIEW: Thirty years ago, investigators isolated and later determined
      the structure of HIV-1 and its envelope proteins. Using techniques that were
      effective with other viruses, they prepared vaccines designed to generate
      antibody or T-cell responses, but they were ineffective in clinical trials. In
      this article, we consider the role of complement in host defense against
      enveloped viruses, the role it might play in the antibody response and why
      complement has not controlled HIV-1 infection. RECENT FINDINGS: Complement
      consists of a large group of cell-bound and plasma proteins that are an integral
      part of the innate immune system. They provide a first line of defense against
      microbes and also play a role in the immune response. Here we review the studies
      of complement-mediated HIV destruction and the role of complement in the HIV
      antibody response. SUMMARY: HIV-1 has evolved a complex defense to prevent
      complement-mediated killing reviewed here. As part of these studies, we have
      discovered that HIV-1 envelope, on administration into animals, is rapidly broken
      down into small peptides that may prove to be very inefficient at provident the
      type of antigenic stimulation that leads to an effective immune response.
      Improving complement binding and stabilizing envelope may improve the vaccine
      response.

PMID- 24670323
TI  - Spectrum of HIV antibodies in vaccine and disease.

PMID- 24670321
TI  - Modulation of HIV-1 immunity by adjuvants.
AB  - PURPOSE OF REVIEW: To summarize the role of adjuvants in eliciting desirable
      antibody responses against HIV-1 with particular emphasis on both historical
      context and recent developments. RECENT FINDINGS: Increased understanding of the
      role of pattern recognition receptors such as Toll-like receptors in recruiting
      and directing the immune system has increased the variety of adjuvant
      formulations being tested in animal models and humans. Across all vaccine
      platforms, adjuvant formulations have been shown to enhance desirable immune
      responses such as higher antibody titers and increased functional activity.
      Although no vaccine formulation has yet succeeded in eliciting broad neutralizing
      antibodies against HIV-1, the ability of adjuvants to direct the immune response
      to immunogens suggests they will be critically important in any successful HIV-1
      vaccine. SUMMARY: The parallel development of adjuvants along with better HIV-1
      immunogens will be needed for a successful AIDS vaccine. Additional comparative
      testing will be required to determine the optimal adjuvant and immunogen regimen
      that can elicit antibody responses capable of blocking HIV-1 transmission.

PMID- 24670324
TI  - Serological assays for emerging coronaviruses: challenges and pitfalls.
AB  - More than a decade after the emergence of severe acute respiratory syndrome
      coronavirus (SARS-CoV) in 2002/2003 the occurrence of a novel CoV termed Middle
      East respiratory syndrome (MERS) CoV challenges researchers and public health
      authorities. To control spread and finally contain novel viruses, rapid
      identification and subsequent isolation of infected individuals and their
      contacts is of utmost importance. Next to methods for nucleic acid detection,
      validated serological assays are particularly important as the timeframe for
      antibody detection is less restricted. During the SARS-CoV epidemic a wide
      variety of serological diagnostic assays were established using multiple methods
      as well as different viral antigens. Even though the majority of the developed
      assays showed high sensitivity and specificity, numerous studies reported on
      cross-reactive antibodies to antigens from wide-spread common cold associated
      CoVs. In order to improve preparedness and responsiveness during future outbreaks
      of novel CoVs, information and problems regarding serological diagnosis that
      occurred during the SARS-CoV should be acknowledged. In this review we summarize
      the performance of different serological assays as well as the applicability of
      the two main applied antigens (spike and nucleocapsid protein) used during the
      SARS-CoV outbreak. We highlight challenges and potential pitfalls that occur when
      dealing with a novel emerging coronavirus like MERS-CoV. In addition we describe
      problems that might occur when animal sera are tested in serological assays for
      the identification of putative reservoirs. Finally, we give a recommendation for
      a serological testing scheme and outline necessary improvements that should be
      implemented for a better preparedness. 

PMID- 24670325
TI  - Calcium-signal facilitates herpes simplex virus type 1 nuclear transport through
      slingshot 1 and calpain-1 activation.
AB  - Herpes simplex virus type 1 (HSV-1) can establish its latency in neurons and is
      associated with virus-induced pathological neurodegeneration in the nervous
      system. Here we show that viral penetration-induced calcium release facilitated
      HSV-1 intracellular trafficking through activating slingshot 1 (SSH), a
      phosphatase regulating actin filament dynamics. More detailed studies revealed
      that phospholipase C gamma 1, and the inositol 1,4,5-trisphosphate receptor
      isoform 1 were required for SSH activation. Besides, calpain-1, a calcium
      dependent cysteine protease, was involved in viral intracellular migration. These
      results may lead to new targets for antiviral therapy. 

PMID- 24670326
TI  - Coronary flow velocity reserve is impaired in hypertensive patients with
      hyperhomocysteinemia.
AB  - Hyperhomocysteinemia (HHcy) is an independent risk factor for coronary artery
      disease. Chronic HHcy induces coronary endothelial injury, and homocysteine (Hcy)
      inhibits insulin sensitivity by inducing endoplasmic reticulum stress in adipose
      tissue. However, the combined effects of chronic HHcy and hypertension on
      coronary artery endothelial function have still remained unclear. Fifty-one
      patients with essential hypertension (HT) were recruited, and were divided into
      nHT group (without HHcy) and H-type HT group (with HHcy). Forty healthy subjects
      were enrolled as controls. We assessed coronary artery endothelial function by
      coronary flow velocity reserve (CFVR). Hcy levels were significantly higher
      (15.60+/-6.58 vs 13.08+/-4.13 MUmol l(-1), P<0.05), whereas CFVR values were
      significantly lower in the HT patients than in the control group (2.88+/-0.70 vs
      3.23+/-0.54, P<0.05). Hcy levels were negatively correlated with CFVR value (r=
      0.578, P<0.01, 95% confidence interval -0.085 to -0.046). The homeostasis model
      assessment-insulin resistance values were significantly higher (3.92+/-2.16 vs
      2.72+/-1.50, P<0.05) , whereas CFVR values were significantly lower in H-type HT
      group than in nHT group (2.31+/-0.31 vs 3.25+/-0.62, P<0.01). Coronary artery
      endothelial function may be impaired in essential hypertensive patients with
      HHcy, and insulin resistance induced by HHcy may contribute to this damage. 

PMID- 24670327
TI  - The Trp64Arg beta3-adrenergic receptor gene polymorphism is associated with
      endothelium-dependent vasodilatation.

PMID- 24670328
TI  - Differential effect of beetroot bread on postprandial DBP according to Glu298Asp
      polymorphism in the eNOS gene: a pilot study.
AB  - Our objective was to investigate whether the presence of Glu298Asp polymorphism
      in the endothelial NO synthase (eNOS) gene differentially affects the
      postprandial blood pressure response to dietary nitrate-rich beetroot bread. A
      randomised, single-blind, controlled, crossover acute pilot study was performed
      in 14 healthy men (mean age: 34+/-9 years) who were retrospectively genotyped for
      Glu298Asp polymorphism (7GG; T carriers 7). Volunteers were randomised to receive
      200 g beetroot-enriched bread (1.1 mmol nitrate) or control bread (no beetroot;
      0.01 mmol nitrate) on two separate occasions 10 days apart. Baseline and
      incremental area under the curve of blood pressure and NOx (nitrate/nitrite) were
      measured for a 6-h postprandial period. A treatment * genotype interaction was
      observed for diastolic blood pressure (P<0.02), which was significantly lower in
      T carriers (P<0.01) after consumption of beetroot bread compared with control
      bread. No significant differences were observed in the GG group. The beneficial
      diastolic blood pressure reduction was observed only in the T carriers of the
      Glu298Asp polymorphism in the eNOS gene after consumption of nitrate-rich
      beetroot bread. These data require confirmation in a larger population group. 

PMID- 24670329
TI  - Redox mechanisms of the beneficial effects of heme oxygenase in hypertension.
AB  - Heme oxygenases, namely heme oxygenase-1 and heme oxygenase-2, have important
      biological functions in vascular homeostasis. Heme oxygenase and its catabolic
      products, including bilirubin and carbon monoxide, have been implicated in blood
      pressure regulation. Increased expression of heme oxygenase exerts multiple
      protective actions against hypertension-induced vascular injuries. However, the
      underlining mechanisms of these effects are not entirely clear. We and others
      have demonstrated that heme oxygenase-1 can modulate production of reactive
      oxygen species, both in vivo and in vitro, from NADPH oxidase, a major enzymatic
      source of reactive oxygen species generation in the vascular wall. NADPH oxidase
      has been implicated in the development of hypertension and hypertension-related
      organ injuries. In this mini review, we summarize our current understanding of
      the interactions between heme oxygenase and NADPH oxidase, and we propose that
      modulation of NADPH oxidase activity by heme oxygenase could be a potential
      mechanism of the beneficial effects of heme oxygenase in hypertension. 

PMID- 24670330
TI  - Dog:cat population ratio is interestingly similar in houses and apartments of
      Southern Brazil.

PMID- 24670331
TI  - Adverse Childhood Experiences (ACEs) questionnaire and Adult Attachment Interview
      (AAI): implications for parent child relationships.
AB  - Although Adverse Childhood Experiences (ACEs) are linked to increased health
      problems and risk behaviors in adulthood, there are no studies on the association
      between ACEs and adults' states of mind regarding their early childhood
      attachments, loss, and trauma experiences. To validate the ACEs questions, we
      analyzed the association between ACEs and emotional support indicators and Adult
      Attachment Interview (AAI) classifications in terms of unresolved mourning
      regarding past loss or trauma and discordant states of mind in cannot classify
      (U/CC) interviews. Seventy-five urban women (41 clinical and 34 community)
      completed a questionnaire on ACEs, which included 10 categories of abuse,
      neglect, and household dysfunction, in addition to emotional support. Internal
      psychological processes or states of mind concerning attachment were assessed
      using the AAI. ACE responses were internally consistent (Cronbach's alpha=.88).
      In the clinical sample, 84% reported>=4 ACEs compared to 27% among the community
      sample. AAIs judged U/CC occurred in 76% of the clinical sample compared to 9% in
      the community sample. When ACEs were>=4, 65% of AAIs were classified U/CC.
      Absence of emotional support in the ACEs questionnaire was associated with 72% of
      AAIs being classified U/CC. As the number of ACEs and the lack of emotional
      support increases so too does the probability of AAIs being classified as U/CC.
      Findings provide rationale for including ACEs questions in pediatric screening
      protocols to identify and offer treatment reducing the intergenerational
      transmission of risk associated with problematic parenting. 

PMID- 24670332
TI  - Assessment of coarse and fine hand motor performance in asymptomatic subjects
      exposed to hand-arm vibration.
AB  - A frequently encountered exposure profile for hand-arm vibration in contemporary
      occupational setting comprises workers with a long history of intermittent
      exposure but without detectable signs of hand-arm vibration syndrome (HAVS). Yet,
      most of the published studies deal with developed HAVS cases, rarely discussing
      the biological processes that may be involved in degradation of manual dexterity
      and grip strength when it can be most beneficial - during the asymptomatic stage.
      In the present paper, a group of 31 male asymptomatic vibration-exposed workers
      (according to the Stockholm Workshop Scale) were compared against 30 male
      controls. They were tested using dynamometry and dexterimetry (modelling coarse
      and fine manual performance respectively) and cold provocation was done to detect
      possible differences in manual performance drop on these tests. The results
      showed reduced manual dexterity but no significant degradation in hand grip
      strength in the exposed subjects. This suggests that intermittent exposure
      profile and small cumulative vibration dose could only lead to a measurable
      deficit in manual dexterity but not hand grip strength even at non-negligible
      A(8) levels and long term exposures.

PMID- 24670333
TI  - Protective effects of oestradiol against cadmium-induced changes in blood
      parameters and oxidative damage in rats.
AB  - The aim of this study was to investigate the protective effects of oestradiol
      (E2, 4 mg kg-1 b.w. i.p.) against cadmium-induced (Cd, 2 mg kg-1 b.w. i.p.) blood
      changes in rats. Cadmium induced a significant decline in haemoglobin,
      haematocrit, and total erythrocyte, lymphocyte, and thrombocyte count, whereas
      total leukocytes and granulocytes increased. A significant increase was also
      observed in serum cholesterol, triglycerides, glucose, AST, and ALT activities,
      whereas total protein and albumin levels dropped significantly. Administration of
      E2 in combination with Cd alleviated most of these adverse effects. In terms of
      oxidative stress, Cd significantly increased oxygen-free radicals (O2 *- and
      H2O2) in neutrophils and lipid peroxidation in erythrocytes, whereas E2 treatment
      reversed these changes to control values. Acute Cd poisoning significantly
      lowered antioxidant enzyme (SOD and CAT) activity and the level of non-enzymatic
      antioxidants (GSH and vitamin E), while increasing in GSSG. Treatments with E2
      reversed Cd-induced effects on the antioxidant defences and significantly lowered
      Cd-induced oxidative damage in erythrocytes. This study suggests that exogenous
      E2 effectively restores redox balance in rat erythrocytes and counters adverse
      haematological and biochemical effects of Cd poisoning. It also improves the
      antioxidant capacity of erythrocytes, acting in synergy with endogenous
      antioxidants.

PMID- 24670334
TI  - Degradation of soil cyanide by single and mixed cultures of Pseudomonas stutzeri
      and Bacillus subtilis.
AB  - The aim of this investigation was to study whether certain bacteria could be used
      for cyanide degradation in soil. The bacteria Pseudomonas stutzeri and Bacillus
      subtilis were selected based on their good growth in a minimal medium containing
      0.8 mg mL-1 potassium cyanide (KCN). In this study we tested their ability to
      reduce cyanide levels in a medium containing 1.5 mg mL-1 of KCN. Although both
      microorganisms reduced cyanide levels, Pseudomonas stutzeri was the more
      effective test organism. Later on, the selected cultures were grown, diluted and
      their various cell concentrations were used individually and in combination to
      test their ability of cyanide degradation in soil samples collected around a
      cassava processing mill. Bacillus subtilis caused degradation of soil cyanide
      from 0.218 mg g-1 soil immediately with an inoculum concentration of 0.1
      (OD600nm) to 0.072 mg g-1 soil after 10 days with an inoculum concentration of
      0.6 (OD600nm) implying a 66.9 % reduction. Pseudomonas stutzeri cell
      concentration of 0.1 (OD600nm) decreased soil cyanide from 0.218 mg g-1 soil
      initially to 0.061 mg g-1 soil after 10 days with an inoculum concentration of
      0.6 (OD600nm) (72 % reduction). The mixed culture of the two bacteria produced
      the best degradation of soil cyanide from 0.218 mg g-1 soil sample with a
      combined inoculum concentration of 0.1 (OD600nm) initially to 0.025 mg g-1 soil
      with a combined inoculum concentration of 0.6 (OD600nm) after 10 days incubation
      resulting in an 88.5 % degradation of soil cyanide. The analysed bacteria
      displayed high cyanide degradation potential and may be useful for efficient
      decontamination of cyanide contaminated sites.

PMID- 24670335
TI  - Risk analysis for the surgical treatment of colorectal cancer in elderly patients
      undergoing scheduled and urgent interventions.
AB  - Due to recorded growth both in living standards and latest researches in
      medicine, proportion of people in old age has significantly improved all over the
      world. Although old age people are several percent of the entire society, number
      of surgeries within the group does not exceed 40%. Also risk of malignant
      neoplasms among old age people, significantly grows. Malignant neoplasm of colon
      appears to be most visible problem in group of people in age over 75 years old.
      The aim of the study was a retrospective analysis of results in treatment of the
      sick over 75 years old, suffering from Malignant neoplasm of colon. Therapy was
      performed in the I Unit of General Surgery and Surgical Oncology in Provinical
      Hospital in Jelenia Gora. MATERIAL AND METHODS: Subject to analysis were 63
      patients that went under operations in years from 2006 to 2010 due to the
      colorectal cancer, who have been divided now into two groups. First group
      included 49 patients treated as per schedule, and the second stood for 14, who
      required urgent treatment. Reference group has involved 20 younger patients,
      treated in urgent and scheduled courses, due to the colon cancer. There are no
      contradictions to emergencies and scheduled surgeries for patients in advanced
      years, suffering from colon cancer. Complications after colon cancer emergencies
      are far more frequent than in case of scheduled surgeries. Death rates among
      patients over 75 years old are far more frequent after emergencies than after
      scheduled surgeries. Concomitant diseases occur the same frequent during
      emergenices as during scheduled operations. During emergencies, it was left side
      of the colon that occured to be infected with cancer more frequent. CONCLUSIONS:
      There is no significant diversity in hospitalization time frames after
      emergencies and scheduled surgeries. Dangerous surgical complications within
      group of older patients, those after emergencies and scheduled surgeries too, are
      far more frequent in comparison to the reference group.

PMID- 24670336
TI  - Mesh repair of umbilical hernia without a visible abdominal scar.
AB  - Experience in the use of Single Incision Laparoscopic Surgery procedures and the
      persistent urge to improve the cosmetic effect have contributed to the
      introduction of mesh repair of an umbilical hernia by means of a small incision
      in the natural position of the umbilicus. The aim of the study was to present the
      surgical technique and assess its postoperative results. MATERIAL AND METHODS:
      During the period between 24.08.2011 and 01.01.2013, twenty-three umbilical
      hernia repair operations with the use of a polypropylene mesh by means of a small
      incision in the natural position of the umbilicus were performed. The synthetic
      material was placed in the preperitoneal space. The wound was closed and the
      umbilicus was reconstructed simultaneously, in order to make the scar invisible.
      Cutaneous stitches were not used. RESULTS: The average duration of the operation
      was 49 minutes. In one case of an obese patient with coexisting linea alba
      dehiscence, hernia recurrence was observed. All wounds healed without
      complications. The cosmetic effect was very good. CONCLUSIONS: Based on the
      presented experience mesh repair of the umbilical hernia by means of a small
      incision in the natural position of the umbilicus contributes essential benefits,
      such as a very good cosmetic effect without consecutive increasing costs, as
      compared to standard treatment by means of an infraumbilical incision.

PMID- 24670337
TI  - Simultaneous TAPP (transabdominal pre-peritoneal technique) for inguinal hernia
      and cholecystectomy - a feasible and safe procedure.
AB  - Inguinal hernia repair and cholecystectomy are amongst the most common surgical
      procedures performed worldwide. In the recent decades, early disease detection
      has notably increased due to easily accessible ultrasound. The aim of the study
      was to assess the safety and the possibility of performing a simultaneous hernia
      repair and cholecystectomy using the laparoscopic approach. MATERIAL AND METHODS:
      Eight patients (M=100%) with inguinal hernia (3 with bilateral hernia) and
      cholelithiasis were included in the study. The presence of gallstones was
      confirmed by imaging. Mean age of the patients was 61.75 years (ranging from 47
      72). Simultaneous laparoscopic cholecystectomy and transabdominal pre-peritoneal
      hernia repair was performed in all patients. Postoperative complications were
      analyzed to assess the safety and feasibility of the procedure. RESULTS: Mean
      operating time was 55 minutes (ranging from 30-60) and average length of stay was
      3.625 days (ranging from 2-7). In order to perform a cholecystectomy, 1-2
      additional trocars were used. No intra-operative complications were observed. At
      a follow-up visit on postoperative day 7, a small hematoma (10 ml of blood was
      punctured) in the right groin was noted in one patient. Another patient developed
      fever postoperatively, treated conservatively with antibiotics. CONCLUSIONS:
      Simultaneous TAPP and cholecystectomy proved to be a safe and feasible procedure.
      Acceptable operating time and hospital stay, as well as lack of influence on the
      length of convalescence, may present an interesting alternative to two separate
      procedures.

PMID- 24670338
TI  - Retrospective analysis of local recurrence rate in breast cancer patients treated
      at the department of surgical oncology in Lodz between 2009 and 2013.
AB  - The aim of the study was to analyze clinicopathological features in breast cancer
      patients with local recurrence (LR). MATERIAL AND METHODS: A retrospective
      analysis of database of breast cancer patients operated on in the Department of
      Surgical Oncology in Lodz from 2 January 2009 to 30 June 2013, identified 1080
      women with primary breast cancer and 11 patients with LR. RESULTS: LR rate was
      0.23% per year. True recurrence (TR) occurred more frequently in patients with
      luminal B molecular subtype, in HER-2 positive and in triple-negative subgroups.
      In one patient with luminal -A subtype new primary (triple negative) occurred. TR
      were noted predominantly in patients with axillary lymph nodes metastases and
      with luminal B subtype who did not receive adjuvant chemotherapy but were given
      only endocrine therapy. LR were observed more frequently in patients who did not
      receive adjuvant radiotherapy or this treatment was delayed. Minimal surgical
      margins in postoperative specimens measured by pathologist were 4-25 mm, mean 9.5
      mm. CONCLUSIONS: The LR rate in patients operated on breast cancer in the
      Department of Surgical Oncology between 2009 and 2013 was low. TR was diagnosed
      in patients with non- luminal A breast cancer despite wide surgical margins,
      especially if the patients did not receive optimal adjuvant systemic treatment or
      radiotherapy was delayed or omitted. Complete cancer excision followed by an
      immediate implementation of optimal adjuvant treatment seems to be crucial
      especially in patients with poor tumor biology.

PMID- 24670339
TI  - Changes in fatigue and physical function following laparoscopic colonic surgery.
AB  - The aim of the study was to describe changes in postoperative fatigue, quality of
      life, physical performance, and body composition in patients undergoing
      laparoscopic colonic cancer surgery. MATERIAL AND METHODS: In a follow-up study
      from 2009-2011 at two regional hospitals in Denmark we examined 62 patients
      having a right hemicolectomy ora sigmoid resection performed. The main outcome
      measures were fatigue level subjectively scored from 1 ("fit") to 10 ("fatigued")
      on a modified visual analogue scale and by objective measurements of hand grip
      and knee extension strength, work capacity, weight, and lean body mass. Quality
      of life was assessed using the SF-36 questionnaire and pain using an ordinal
      scale. Patients were examined preoperatively, 1-2 and 4 weeks postoperatively.
      RESULTS: Eight patients (13%) were converted to open surgery and the median
      bleeding (95% confidence interval of the median) was 75 (50-100) ml. One to two
      weeks after surgery the fatigue level and pain when moving had increased
      significantly (p=0.0011 and p=0.0002 respectively) and the SF-36 physical
      component quality of life score decreased (p<0.0001) when compared to
      preoperatively. However, at 4 weeks postoperatively fatigue level, pain, and
      quality of life scores were at the preoperative level. There were no significant
      changes from preoperatively to postoperatively in any of the measures of physical
      performance, whereas there was a slight reduction in weight and lean body mass
      after the operation. CONCLUSIONS. Laparoscopic colonic cancer surgery was
      associated with a short lasting increased fatigue and pain and reduced quality of
      life, but no significant reduction in physical performance after surgery.

PMID- 24670340
TI  - Comparison of effectiveness of electrocautery and phenol application in partial
      matricectomy after partial nail extraction in the treatment of ingrown nails.
AB  - Ingrowing nail also known as onychocryptosis is a common health problem. This
      disease mostly affects young people, often carrying a considerable amount of
      socio-economic implications. It's foot problem that usually manifests as
      inflammation of tissue along the side of a toenail. The aim of the study was to
      asses and to compare effectiveness of electrocautery and phenol application in
      partial matrixectomy after partial nail extraction in the treatment of ingrown
      toenails. MATERIAL AND METHODS: The group of 60 patients with ingrowing toenail
      which was randomized into two groups underwent partial matrixectomy in surgical
      outpatient clinic between 2009-2013. This group of patients was under surgical
      observation for 100 days in outpatient clinic. RESULTS: In all operated patients
      we obtained surgical success however we had 13 recurrences during the follow up
      period, 5 in the phenolization group and 8 in the electrocoagulation group.
      CONCLUSIONS: There was statistically significant difference between these two
      techniques, which indicated that matrix phenolization is connected with shortened
      healing time vs the matrix electrocoagulation.

PMID- 24670341
TI  - Multiple colon perforation as a fatal complication during treatment of metastatic
      melanoma with ipilimumab - case report.
AB  - Ipilimumab, an anticancer drug, is an anti-CTLA4 monoclonal antibody. It is used
      in treatment of disseminated melanoma. Therapy is associated with high risk of
      complications. One of the most serious, although one of the rarest is perforation
      of gastrointestinal tract. In this case report we describe a 52-year old male,
      with disseminated melanoma with unknown starting point, treated with anti- CTLA4
      monoclonal antibody. After 3rd dose of drug administration, bloody diarrhea and
      acute abdominal pain occurred as a symptom of gastrointestinal perforation. A
      single perforation was sutured during laparotomy. Symptoms of acute abdomen
      returned after 10 days. Pus-faecalperitonitis, symptoms of necro-hemorrhagic
      colitis and multilocal perforation of the colon were found during relaparotomy.
      Pancolectomy with end ileostomy was performed. Few hours since relaparotomy
      pacient died due to multiple organ failure. The purpose of this case report is to
      draw attention to a risk of multilocal colon perforation in patient treated with
      ipilumumab.

PMID- 24670342
TI  - Bilateral renal cell carcinoma with bilateral synchronous adrenal gland
      metastases - a case report.
AB  - The authors reported a case of a 52-year-old patient with bilateral synchronous
      renal cell carcinoma synchronously disseminated in adrenal glands is presented.
      The patient underwent surgical treatment: radical nephrectomy on the right side,
      bilateral adrenectomie on the right and partial nephrectomy on the left side.
      Five years after surgery, patient is in complete remission.

PMID- 24670343
TI  - Preoperative fasting - is it really necessary?

PMID- 24670344
TI  - Vitamin D intoxication in two brothers: be careful with dietary supplements.
AB  - Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children,
      has renal, cardiac and neurological consequences. Iatrogenic or accidental
      administrations are the most common causes. We present two cases of
      hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12
      year-old boy was hospitalised for abdominal pain, constipation and vomiting.
      Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25
      OH VitD level was very high and parathyroid hormone was suppressed. Renal
      ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a
      progressive reduction of calcium levels. His brother, who was receiving the same
      treatment, was hospitalised although asymptomatic. Normal serum calcium and renal
      function were revealed, while 25-OH VitD was high and parathyroid hormone was
      suppressed. Renal ultrasound was within the normal range. Examination of the VitD
      content of the over-the-counter supplement revealed a higher amount than
      declared. VitD administration implies several risks and must be prescribed only
      when needed and under strict medical control.

PMID- 24670345
TI  - Transient diabetes insipidus in a preterm neonate and the challenge of
      desmopressin dosing.
AB  - BACKGROUND: As neonatal central diabetes insipidus is rare in preterm neonates
      with intraventricular hemorrhage (IVH), very little is known about dosing and the
      route of administration of desmopressin treatment. CASE REPORT: We present a
      preterm neonate born at 29 weeks' gestation. Within 24 h, she developed bilateral
      IVH with subsequent post-hemorrhagic hydrocephalus. On the 3rd postnatal day, she
      developed diabetes insipidus for which she was intranasally administered 0.2 mg
      desmopressin. This resulted in oliguria with several hours of anuria and a 25
      point drop in sodium levels within 15 h. CONCLUSION: The determination of the
      desmopressin dose in a preterm neonate is a challenge and there is no consistent
      literature about the dosing or the route of administration. We suggest starting
      with a low dose of intranasal desmopressin (0.05-0.1 MUg) and titrate in
      accordance with clinical and laboratory parameters.

PMID- 24670346
TI  - Vitamin D intake and premature infants with intraventricular hemorrhage: how
      advisable is it?

PMID- 24670347
TI  - The methanol-soluble fraction of Millettia macrophylla (Fabaceae) stem bark
      endowed with estrogenic properties has adverse effects on the male reproductive
      system of Wistar rats.
AB  - BACKGROUND: The use of traditional medicinal plants to treat various diseases is
      common in Sub-Saharan African countries, including Cameroon. Millettia
      macrophylla, one of such plants, was previously found to exhibit estrogenic
      properties in female Wistar rats. However, its effects on the male reproductive
      system are unknown. Based on literature evidence that phytoestrogens impair male
      sexual behavior, we aimed at assessing the effect of the extracts of M.
      macrophylla stem bark on the male reproductive system of Wistar rats. MATERIALS
      AND METHODS: We evaluated the effects of the dichloromethane (DCM) and methanol
      (MeOH) soluble fractions of M. macrophylla stem bark on male rat sexual behavior,
      as well as androgen-dependent parameters for 60 days. RESULTS: Data showed a
      significant decrease (p<0.05) in the wiring-touch frequency, mount frequency,
      intromission frequency, ejaculatory frequency, penile-licking frequency, and
      computed indices of sexual behavior, throughout the experimental period, as well
      as a significant increase (p<0.001) in mount, intromission, and ejaculatory
      latencies as well as post-ejaculatory interval. Moreover, we observed a
      significant decrease (p<0.05) in the androgen-dependent sexual parameters
      evaluated. The DCM extract did not induce significant effects on the assessed
      parameters. CONCLUSIONS: These results suggest that long-term exposure to the
      estrogenic MeOH fraction of M. macrophylla stem bark negatively alters sexual
      behavior and spermatogenesis.

PMID- 24670348
TI  - Fast real-time monitoring of entacapone crystallization and characterization of
      polymorphs via Raman spectroscopy, statistics and SWAXS.
AB  - Crystallization of the drug entacapone from binary solvent mixtures was monitored
      in situ using a Raman optical probe. The recorded Raman spectra and statistical
      analysis, which included the principal components method and indirect hard
      modeling made it possible to estimate the starting point of crystallization, to
      assess crystallization temperatures and to provide information on the polymorphic
      content of the mixture. It was established that crystallization temperatures were
      proportional to the volume content of the solvent in mixtures. The samples were
      also evaluated off-line via Raman spectroscopy and SWAXS. The collected data
      showed the presence of forms b and g in all solvent mixtures. In a
      toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the
      forms A, D or a was also indicated by SWAXS. The results have shown that the
      presence of a particular polymorph is strongly dependent on the nature and
      portion of the solvent in the binary solvent mixture.

PMID- 24670349
TI  - Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in
      pharmaceutical formulations: Application of quinone-based fluorophores and
      enhanced native fluorescence.
AB  - Quinone-based fluorophores and enhanced native fluorescence techniques were
      applied for a fast quantitative analysis of gemifloxacin mesylate (GEM) and
      linezolid (LIN) in pharmaceutical formulations. For this purpose, three
      sensitive, accurate and precise spectrofluorimetric methods were developed. GEM,
      as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A)
      and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B) as p-electron acceptors,
      forming charge transfer complexes that exhibit high fluorescence intensity at 441
      and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on
      measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5) at
      380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence
      intensity were optimized. Linearity was obtained over concentration ranges 50
      500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed
      methods were validated and successfully applied for determination of the cited
      drugs in tablets.

PMID- 24670350
TI  - Investigation of in situ gelling alginate formulations as a sustained release
      vehicle for co-precipitates of dextromethrophan and Eudragit S 100.
AB  - Alginate vehicles are capable of forming a gel matrix in situ when they come into
      contact with gastric medium in the presence of calcium ions. However, the gel
      structure is pH dependent and can break after gastric emptying, leading to dose
      dumping. The aim of this work was to develop modified in situ gelling alginate
      formulations capable of sustaining dextromethorphan release throughout the
      gastrointestinal tract. Alginate solution (2 %, m/m) was used as a vehicle for
      the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared
      by dissolving the drug and polymer in acetone. The organic solvent was then
      evaporated and the deposited solid matrix was micronized, sieved and dispersed in
      alginate solution to obtain candidate formulations. The release behavior of
      dextromethorphan was monitored and evaluated in a medium simulating the gastric
      and intestinal pH. Drug-polymer compatibility and possible solid-state
      interactions suggested physical interaction through hydrogen bonding between the
      drug and the polymer. A significant decrease in the rate and extent of
      dextromethorphan release was observed with increasing Eudragit S 100
      concentration in the prepared particles. Most formulations showed sustained
      release profiles similar to that of a commercial sustained-release liquid based
      on ion exchange resin. The release pattern indicated strict control of drug
      release both under gastric and intestinal conditions, suggesting the potential
      advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the
      problem of dose dumping after the rupture of the pH dependent alginate gels.

PMID- 24670351
TI  - Comparative bioavailability of two oral formulations of clopidogrel:
      determination of clopidogrel and its carboxylic acid metabolite (SR26334) under
      fasting and fed conditions in healthy subjects.
AB  - Two randomized, single dose, 2-period, 2-sequence crossover studies were
      conducted to evaluate the comparative bioavailability of two clopidogrel
      formulations under fasting and fed conditions. Assessment of bioequivalence was
      based upon measurement of plasma concentrations of the parent drug, clopidogrel,
      and its major (inactive) metabolite, clopidogrel carboxylic acid, using improved
      methanol-free extraction. Bioequivalence of Krka's formulation to the innovator's
      formulation was demonstrated under both fasting and fed conditions on 205
      volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and
      its main metabolite were well within the acceptance range of 80.00 to 125.00 %.
      Food substantially increased the bioavailability of clopidogrel from both
      formulations, while no effect of food on the extent and rate of exposure to the
      metabolite was observed. The effect of food was comparable between the two
      formulations, as indicated by the same direction and rank of food impact on the
      bioavailability of both formulations.

PMID- 24670352
TI  - High throughput microwell spectrophotometric assay for olmesartan medoxomil in
      tablets based on its charge-transfer reaction with DDQ.
AB  - The study describes the development and validation of a new microwell-based
      spectrophotometric assay for determination of olmesartan medoxomil (OLM) in
      tablets. The formation of a colored charge-transfer (CT) complex between OLM as
      an n-electron donor and 2,3-dichloro- -5,6-dicyano-1,4-benzoquinone (DDQ) as a p
      electron acceptor was investigated, and employed as the basis for the development
      of the new assay. The proposed assay was conducted in 96-microwell plates. The
      absorbance of the colored-CT complex was measured at 460 nm with a microplate
      reader. Optimum conditions of the reaction and the analytical procedures of the
      assay were established. Under the optimum conditions, a linear relationship with
      a good correlation coefficient was found between the absorbance and the
      concentration of OLM in the range of 2-200 MUg per well. The limits of detection
      and quantitation were 0.53 and 1.61 MUg per well, respectively. No interference
      was observed from the excipients present in OLM tablets or from
      hydrochlorothiazide and amlodipine besylate that were co-formulated with OLM in
      some of its formulations. The assay was successfully applied to the analysis of
      OLM in tablets with good accuracy and precision. The assay described herein has a
      great practical value in the routine analysis of OLM in quality control
      laboratories, since it has a high throughput property and consumes low volumes of
      organic solvent. It thus offers a reduction in the exposure of analysts to the
      toxic effects of organic solvents, as well as a reduction in the cost of
      analysis.

PMID- 24670354
TI  - Some variables affecting the characteristics of Eudragit E-sodium alginate
      polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride.
AB  - Eudragit E (EE)-sodium alginate (SA) polyelectrolyte complexes (PECs) were
      prepared at pH 4 and 5.8 using sodium alginate of high (SAH) and low viscosity
      (SAL). The optimum EE-SA complexation mass ratio was determined using viscosity
      measurements. Interactions between EE and SA in PECs were characterized by
      Fourier transform infra-red spectroscopy (FT-IR) and differential scanning
      calorimetry (DSC). Diltiazem hydrochloride (DTZ HCl) tablets were prepared using
      the prepared EE-SA PECs and their physical mixtures at different ratios as
      matrices. Tablets were evaluated for swelling characteristics and in vitro drug
      release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3) as
      matrices were effective in achieving sustained release of DTZ HCl, where the
      percent drug released was significantly (p < 0.05) decreased compared to that
      from tablets either containing the same ratios of EE-SAL physical mixtures or the
      preformed EE- -SAH and EE-SAL PECs.

PMID- 24670353
TI  - Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions:
      comparative study into the effect of aluminium, calcium, zinc and iron on drug
      solubility and dissolution.
AB  - Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co
      administered with metallic ion containing preparations. In our previous study,
      physicochemical interaction between ciprofloxacin and ferrous sulphate was
      successfully simulated in vitro. In the present work, comparative in vitro
      ciprofloxacin solubility and dissolution studies were performed in the reactive
      media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid
      phases collected from the dissolution vessel with aluminium hydroxide, calcium
      carbonate and zinc sulphate were investigated for their properties. The results
      obtained indicate that different types of adducts may form and retard
      ciprofloxacin solubility and dissolution. In the case of aluminium, no phase
      changes were observed. The solid phase generated in the presence of calcium
      carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new
      complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 * nH2O stoichiometry was
      generated in the presence of relatively high concentrations of ciprofloxacin
      hydrochloride and zinc sulphate, indicating that small volume dissolution
      experiments can be useful for biorelevant dissolution tests.

PMID- 24670355
TI  - Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy
      via regulation of myocardial calcium handling proteins.
AB  - C57BL/6 mice with dilated cardiomyopathy (DCM) were randomly divided to receive
      placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment,
      mice with dilated cardiomyopathy developed serious cardiac dysfunction
      characterized by significantly enhanced left ventricular end-diastolic diameter
      (LVIDd), decreased left ventricular ejection fraction (LVEF) as well as left
      ventricular short axis fractional shortening (LVFS), accompanied with enlarged
      cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic
      peptide (NT-proBNP) and plasma angiotensin II (AngII) concentration. Moreover,
      myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2) activity was decreased. The
      ratio of phosphorylated phospholamban (PLB) to total PLB decreased significantly
      with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2) expression.
      Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated
      cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to
      total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the
      expressions of myocardium angiotensin II type 1 receptor (AT1R) and protein
      kinase C (PKC)b2. The possible underlying mechanism might be the regulation of
      myocardial AT1R-PKCb2-Ca2+ handling proteins.

PMID- 24670356
TI  - GSTP1, GSTM1 and GSTT1 genetic polymorphisms and total serum GST concentration in
      stable male COPD.
AB  - The aim of this study was to test the hypothesis that glutathione- S-transferase
      (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were
      determined by DNA methods and GST activity spectrophotometrically in older male
      Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n =
      30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes
      and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The
      odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant
      homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In
      this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and
      heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic
      contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1
      null genotypes were not disease associated. Serum GST was not associated with GST
      genotypes and COPD or smoking history in our study subjects. Conclusions drawn
      from the study should be further supported and clarified by studies with larger
      sample sizes.

PMID- 24670357
TI  - The effect of diclofenac on proliferation and production of growth factors by
      endothelial cells (HMEC-1) under hypoxia and inflammatory conditions.
AB  - Diclofenac belongs to non-steroidal anti-inflammatory drugs (NSAIDs) and non
      selective COX inhibitors. The aim of this study was to examine the effect of
      diclofenac on endothelial cell proliferation under the influence of hypoxia or
      inflammatory conditions. Another goal was to check whether diclofenac modulates
      the secretion of angiogenic factors such as VEGF and bFGF in human microvascular
      endothelial cells (HMEC-1) in the presence of CoCl2 or lipopolysaccharide (LPS),
      which could influence the endothelial cells in an autocrine manner or other cells
      in a paracrine manner. HMEC-1 cells were treated with 0.1 and 0.3 mmol L-1
      diclofenac in the presence of 100 MUg mL-1 LPS or 200 MUmol L-1 CoCl2. Diclofenac
      decreased cell viability under hypoxia and inflammatory conditions. The
      stimulation of bFGF secretion by LPS in microvascular endothelial cells (HMEC-1
      cell) was attenuated by diclofenac. Diclofenac increased the secretion of VEGF
      induced by LPS and hypoxia.

PMID- 24670359
TI  - The quantification of HER2 and MYC gene fragments in cell-free plasma as putative
      biomarkers for gastric cancer diagnosis.
AB  - BACKGROUND: This study aimed to investigate the significance of circulating HER2
      and MYC gene fragments quantification in the diagnosis of gastric cancer.
      METHODS: Levels of HER2 and MYC genes were evaluated by fluorescence in situ
      hybridization and real-time PCR in 81 gastric cancer tissues, and by real-time
      PCR in 36 gastritis tissues. Real-time PCR for HER2 and MYC products was also
      performed on 184 plasma samples from 81 gastric cancers, eight gastric adenomas,
      63 gastritis patients, and 32 healthy individuals. RESULTS: HER2/HBB and MYC/HBB
      ratios in tissue and cell-free plasma from gastric cancer patients were
      significantly higher than those of gastritis tissue and cancer-free individuals.
      An optimized cut-off value of plasma target gene to HBB ratio, used to
      differentiate cancer patients from cancer-free individuals, was evaluated using
      receiver operating characteristic (ROC) curves. Values of 2.0 were calculated for
      HER2 [area under the ROC curve (AUC), 0.760] and 2.725 for MYC (AUC, 0.767). A
      combination model of HER2 and MYC provided a better differentiation condition
      than that for HER2 or MYC only (AUC, 0.850). HER2/HBB ratios in plasma from
      gastric cancer patients correlated with MYC/HBB ratios. CONCLUSIONS: Our findings
      suggest that the measurement of plasma HER2 and MYC gene levels could improve the
      screening of gastric cancer.

PMID- 24670360
TI  - Standardization of DiaSorin and Roche automated third generation PTH assays with
      an International Standard: impact on clinical populations.
AB  - BACKGROUND: Standardization of parathyroid hormone (PTH) assays is a major issue,
      especially in hemodialyzed (HD) patients. Two automated third generation PTH
      assays (Roche Elecsys and DiaSorin Liaison) are now available. These assays are
      specific for the (1-84) PTH and do not cross-react with the (7-84) fragment,
      contrary to second generation (intact) assays. We aimed to calibrate the two
      methods against the WHO International PTH Standard (IS) 95/646 to see if the two
      assays could provide comparable results in a population of healthy subjects, HD
      patients and patients suffering from primary hyperparathyroidism (PHP). METHODS:
      We selected 79 healthy subjects and two populations of patients presenting PTH
      disorders: 56 HD and 27 PHP patients. We reconstituted the IS in a pool of human
      serum containing undetectable levels of 1-84 PTH and prepared 13 serum standards
      ranging from 0 to 2000 pg/mL. The standards were run on the two instruments to
      calibrate the assays on the IS. The different populations were run before and
      after restandardization. RESULTS: As these kits were differently calibrated, the
      results obtained after restandarization were significantly different.
      Restandardization process improved concordance between assays and, taking the
      analytical variability of the two kits into account, the results could be
      considered to be similar. CONCLUSIONS: Restandardization of automated third
      generation PTH assays with the WHO 1-84 PTH Standard significantly reduces inter
      method variability. Reference ranges and raw values are totally transposable from
      one method to the other in healthy subjects, but also in diseased patients, e.g.,
      with HD or those suffering from PHP.

PMID- 24670358
TI  - The leader proteinase of foot-and-mouth disease virus: structure-function
      relationships in a proteolytic virulence factor.
AB  - The leader proteinase (Lpro) of the foot-and-mouth disease virus inhibits the
      host innate immune response by at least three different mechanisms. The most well
      characterised of these is the prevention of the synthesis of cytokines such as
      interferons immediately after infection, brought about by specific proteolytic
      cleavage of the eukaryotic initiation factor 4G. This prevents the recruitment of
      capped cellular mRNA; however, the viral RNA can be translated under these
      conditions. The two other mechanisms are the induction of NF-kappaB cleavage and
      the deubiquitination of immune signalling molecules. This review focuses on the
      structure-function relationships in Lpro responsible for these widely divergent
      activities.

PMID- 24670361
TI  - Advanced tools for BRCA1/2 mutational screening: comparison between two methods
      for large genomic rearrangements (LGRs) detection.
AB  - BACKGROUND: Currently, multiplex ligation-dependent probe amplification (MLPA) is
      the most commonly used technique for the detection of large genomic
      rearrangements (LGRs) in the BRCA1/2 genes. However, a very fast assay, the
      BRCA1/2 multiplex amplicon quantification (MAQ), has been recently developed by
      Multiplicom. METHODS: As no data regarding the application of MAQ method to
      BRCA1/2 genes are available in literature, here we compared for the first time
      the performance of the MAQ assay with MLPA by using several positive BRCA1/2 LGRs
      DNA samples (previously tested by MLPA). RESULTS: MAQ method was able to detect
      all BRCA1/2 LGRs and no false-positive or -negative results were obtained in
      independent repetitive experiments. CONCLUSIONS: We can affirm that MAQ, as well
      as MLPA method, results to be valid and reproducible tools for molecular
      diagnostics and we are confident that this assay can be used for BRCA1/2
      mutational screening as a fast and safe alternative to MLPA, particularly in the
      first line of analysis.

PMID- 24670362
TI  - Shockwave loading of mechanochemically active polymer coatings.
AB  - Thin films of mechanochemically active polymer were subjected to laser-generated,
      high amplitude acoustic pulses. Stress wave propagation through the film produced
      large amplitude stresses (>100 MPa) in short time frames (10-20 ns), leading to
      very high strain rates (ca. 1 * 10(7) to 1 * 10(8) s(-1)). The polymer system,
      spiropyran (SP)-linked polystyrene (PS), undergoes a force-induced chemical
      reaction causing fluorescence and color change. Activation of SP was evident via
      a fluorescence signal in thin films subject to high strain-rates. In contrast,
      quasi-static loading of bulk SP-linked PS samples failed to result in SP
      activation. Mechanoresponsive coatings have potential to indicate deformation
      under shockwave loading conditions. 

PMID- 24670363
TI  - Renal replacement therapy for critically ill patients: an intermittent
      continuity.
AB  - Choice of the right renal replacement therapy for severe acute kidney injury in
      critically ill patients has been investigated many times in the last two decades.
      Although some questions have been answered, in current practice many different
      approaches are still used in the ICU. One basic and important issue is the
      frequency of renal replacement delivery: apart from pathophysiological
      speculations, in terms of hard outcomes (namely mortality and length of hospital
      stay) should dialysis be delivered continuously or intermittently? The authors of
      the CONVINT study provided a (last) response to this debate: in expert hands, the
      two treatments provide similar outcomes. This study confirms previous studies and
      is also important for other aspects, such as the possibility that the two
      modalities are complementary and may be indicated for different purposes.

PMID- 24670364
TI  - Inositol pyrophosphates mediate the effects of aging on bone marrow mesenchymal
      stem cells by inhibiting Akt signaling.
AB  - INTRODUCTION: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been
      proposed as an ideal autologous stem cell source for cell-based therapy for
      myocardial infarction (MI). However, decreased viability and impaired function of
      aged MSCs hampered the therapeutic efficacy of engrafted MSCs, and the underlying
      mechanisms remain unclarified. Here, we investigated the role of inositol
      phosphates 6 kinase (IP6Ks) inhibition on the therapeutic efficacy of BM-MSCs and
      its underlying mechanism. METHODS: BM-MSCs isolated from young (8-week-old) or
      aged (18-month-old) donor male C57BL/6 mice, were subjected to hypoxia and serum
      deprivation (H/SD) injury with or without administration of inositol phosphates 6
      kinase (IP6Ks) inhibitor TNP (10 MUM). MSC apoptosis induced by H/SD was
      determined by flow cytometry and TUNEL assays. Protein expressions were evaluated
      by Western blot assay. Furthermore, the paracrine effects of MSCs were measured
      by reverse transcriptase-polymerized chain reaction (RT-PCR) and enzyme-linked
      immunosorbent assay (ELISA) analyses. RESULTS: Aged BM-MSCs exhibited more
      Inositol pyrophosphate 7 (IP7) production, compared with young BM-MSCs.
      Meanwhile, the expression of phospho-Akt (Thr308) was significantly decreased in
      the aged MSCs, resulting in enhanced Bad activation and decreased Bax/Bcl-2
      ratio. Moreover, the apoptosis in aged BM-MSCs was increased, compared with young
      BM-MSCs. Furthermore, TNP administration significantly inhibited IP7 production
      and increased the phosphorylation of Akt under both normoxic and hypoxic
      conditions. Meanwhile, IP6Ks inhibition reduced apoptotic index of aged MSCs,
      associated with decreased expressions of pro-apoptotic proteins Bax and Bad and
      increased anti-apoptotic protein Bcl-2. The expressions of angiogenic factors,
      including VEGF, bFGF, IGF-1 and HGF, were decreased in MSCs from aged mice. In
      addition, TNP administration enhanced the paracrine efficiency of aged BM-MSCs
      under normoxic and hypoxic conditions. CONCLUSIONS: This study demonstrates for
      the first time that IP6Ks and IP7 play critical role in the aging related
      vulnerability to hypoxic injury and impaired paracrine efficiency of BM-MSCs,
      which is associated with impaired Akt activation.

PMID- 24670365
TI  - MicroRNAs in the Regulation of MMPs and Metastasis.
AB  - MicroRNAs are integral molecules in the regulation of numerous physiological
      cellular processes including cellular differentiation, proliferation, metabolism
      and apoptosis. Their function transcends normal physiology and extends into
      several pathological entities including cancer. The matrix metalloproteinases
      play pivotal roles, not only in tissue remodeling, but also in several
      physiological and pathological processes, including those supporting cancer
      progression. Additionally, the contribution of active MMPs in metastatic spread
      and the establishment of secondary metastasis, via the targeting of several
      substrates, are also well established. This review focuses on the important
      miRNAs that have been found to impact cancer progression and metastasis through
      direct and indirect interactions with the matrix metalloproteinases. 

PMID- 24670366
TI  - Stat3 and gap junctions in normal and lung cancer cells.
AB  - Gap junctions are channels linking the interiors of neighboring cells. A
      reduction in gap junctional intercellular communication (GJIC) correlates with
      high cell proliferation, while oncogene products such as Src suppress GJIC,
      through the Ras/Raf/Erk and other effector pathways. High Src activity was found
      to correlate with high levels of the Src effector, Signal Transducer and
      Activator of Transcription-3 (Stat3) in its tyrosine-705 phosphorylated, i.e.,
      transcriptionally activated form, in the majority of Non-Small Cell Lung Cancer
      lines examined. However, Stat3 inhibition did not restore GJIC in lines with high
      Src activity. In the contrary, Stat3 inhibition in normal cells or in lines with
      low Src activity and high GJIC eliminated gap junctional communication.
      Therefore, despite the fact that Stat3 is growth promoting and in an activated
      form acts like an oncogene, it is actually required for junctional permeability. 

PMID- 24670367
TI  - Structural pathways of cytokines may illuminate their roles in regulation of
      cancer development and immunotherapy.
AB  - Cytokines are messengers between tissues and the immune system. They play
      essential roles in cancer initiation, promotion, metastasis, and immunotherapy.
      Structural pathways of cytokine signaling which contain their interactions can
      help understand their action in the tumor microenvironment. Here, our aim is to
      provide an overview of the role of cytokines in tumor development from a
      structural perspective. Atomic details of protein-protein interactions can help
      in understanding how an upstream signal is transduced; how higher-order
      oligomerization modes of proteins can influence their function; how mutations,
      inhibitors or antagonists can change cellular consequences; why the same protein
      can lead to distinct outcomes, and which alternative parallel pathways can take
      over. They also help to design drugs/inhibitors against proteins de novo or by
      mimicking natural antagonists as in the case of interferon-gamma. Since the
      structural database (PDB) is limited, structural pathways are largely built from
      a series of predicted binary protein-protein interactions. Below, to illustrate
      how protein-protein interactions can help illuminate roles played by cytokines,
      we model some cytokine interaction complexes exploiting a powerful algorithm
      (PRotein Interactions by Structural Matching-PRISM). 

PMID- 24670369
TI  - Nanometer-scale elongation rate fluctuations in the Myriophyllum aquaticum
      (Parrot feather) stem were altered by radio-frequency electromagnetic radiation.
AB  - The emission of radio-frequency electromagnetic radiation (EMR) by various
      wireless communication base stations has increased in recent years. While there
      is wide concern about the effects of EMR on humans and animals, the influence of
      EMR on plants is not well understood. In this study, we investigated the effect
      of EMR on the growth dynamics of Myriophyllum aquaticum (Parrot feather) by
      measuring the nanometric elongation rate fluctuation (NERF) using a statistical
      interferometry technique. Plants were exposed to 2 GHz EMR at a maximum of 1.42
      Wm(-2) for 1 h. After continuous exposure to EMR, M. aquaticum plants exhibited a
      statistically significant 51 +/- 16% reduction in NERF standard deviation.
      Temperature observations revealed that EMR exposure did not cause dielectric
      heating of the plants. Therefore, the reduced NERF was due to a non-thermal
      effect caused by EMR exposure. The alteration in NERF continued for at least 2.5
      h after EMR exposure and no significant recovery was found in post-EMR NERF
      during the experimental period. 

PMID- 24670368
TI  - Can biomarker assessment on circulating tumor cells help direct therapy in
      metastatic breast cancer?
AB  - Circulating tumor cell (CTC) count has prognostic significance in metastatic
      breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies
      on CTCs have often been limited by a low number of CTCs isolated from a high
      background of leukocytes. Improved enrichment techniques are now allowing
      molecular characterisation of single CTCs, whereby molecular markers on single
      CTCs may provide a real-time assessment of tumor biomarker status from a blood
      test or "liquid biopsy", potentially negating the need for a more invasive tissue
      biopsy. The predictive ability of CTC biomarker analysis has predominantly been
      assessed in relation to HER2, with variable and inconclusive results. Limited
      data exist for other biomarkers, such as the estrogen receptor. In addition to
      the need to define and validate the most accurate and reproducible method for CTC
      molecular analysis, the clinical relevance of biomarkers, including gain of HER2
      on CTC after HER2 negative primary breast cancer, remains uncertain. This review
      summarises the currently available data relating to biomarker evaluation on CTCs
      and its role in directing management in metastatic breast cancer, discusses
      limitations, and outlines measures that may enable future development of this
      approach. 

PMID- 24670370
TI  - Calcium carbonate breath test for non-invasive estimation of gastric acid
      secretion.
AB  - Gastric acid measurement is useful in assessing the effectiveness of
      antisecretory drugs, however, the conventional tests involve invasive nasogastric
      intubation. Orally administered 13C-labeled calcium carbonate (Ca13CO3) reacts
      with gastric acid to produce 13C-labeled carbon dioxide (13CO2), which is then
      excreted in the breath. The objective of this study was to evaluate the
      suitability of Ca13CO3 breath test for estimating gastric acid secretion in human
      noninvasively. First, the Ca13CO3 breath test and the measurement of pooled
      gastric acid under a fasting condition were performed in 6 healthy volunteers to
      evaluate the correlation between the two parameters. Next, endoscopic gastric
      acid collection and the Ca13CO3 breath test were performed on different days
      after pentagastrin injection in 20 subjects to evaluate the correlation between
      the tests and the reproducibility. Finally, the same studies were repeated in 4
      subjects before and after 1-week rabeprazole, a proton pump inhibitor,
      administration. The maximum CO2 concentration (Cmax) correlated very well with
      the amount of pooled gastric acid (r = 0.95), suggesting that Ca13CO3 breath test
      values well reflected the fasting intragastric acidity. The 13CO2 concentration
      after pentagastrin injection correlated well with pentagastrin-stimulated maximal
      acid output (r = 0.79 at 20 min). The reproducibility of the Ca13CO3 breath test
      under pentagastrin-stimulation was good (coefficient of variation = 0.11).
      Rabeprazole administration markedly reduced the values of the Ca13CO3 breath
      test, suggesting that it can sensitively assess the efficacy of rabeprazole. The
      Ca13CO3 breath test can potentially be a useful method for non-invasive
      estimation for gastric acid secretion in human.

PMID- 24670371
TI  - One Country, Two Cultures: Are Hong Kong Mock Jurors "Mainlandized" by the
      Predominant Chinese Criminal Justice Concept of Confession?
AB  - Over-reliance on confession has had a long history in the Chinese criminal
      justice system. Recent high-profile wrongful conviction cases have raised public
      awareness of the coercive and torturous methods used to extract confessions.
      Despite the return of Hong Kong to Chinese sovereignty, Hong Kong remains a
      common law jurisdiction and the most serious criminal offences are tried by a
      jury. The present study empirically examines the relative impact of DNA evidence,
      confession, eyewitness testimony, and victim testimony in a Hong Kong-Chinese
      mock juror sample. The results show that the participants placed greater value on
      DNA evidence than on confession, and placed the lowest value on testimonial
      evidence. It is argued that the situation of "one country, two cultures" remains
      strong: Whereas participants are still influenced by the Chinese criminal justice
      concept of confession, their judgment is still predominately influenced by the
      scientific evidence as commonly practiced in the West. Thus, no solid evidence
      has been found to confirm the emergence of mainlandization in Hong Kong's
      criminal justice system. 

PMID- 24670372
TI  - Alcohol consumption over time and risk of death: a systematic review and meta
      analysis.
AB  - The results from the few cohort studies that have measured usual alcohol
      consumption over time have not been summarized. We therefore conducted a
      systematic review and meta-analysis to quantify mortality risk. Pertinent studies
      were identified by searching the Medline, Web of Science, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL) Plus, and Scopus databases through
      August 2012 using broad search criteria. Studies reporting relative mortality
      risks for quantitatively defined categories of alcohol consumption over time were
      eligible. Nine cohort studies published during 1991-2010 (comprising 62,950
      participants and 10,490 deaths) met the inclusion criteria. For men, there was
      weak evidence of lower mortality risk with low levels of alcohol intake over time
      but higher mortality risk for those with intakes over 40 g/day compared with
      abstainers using a random-effects model (P for nonlinearity = 0.02). The pooled
      relative risks were 0.90 (95% confidence interval: 0.81, 0.99) for 1-29 g/day,
      1.19 (95% confidence interval: 0.89, 1.58) for 30-59 g/day, and 1.52 (95%
      confidence interval: 0.78, 2.98) for 60 or more g/day compared with abstention.
      There was moderate between-study heterogeneity but no evidence of publication
      bias. Studies including women were extremely scarce. Our findings include a
      curvilinear association between drinking over time and mortality risk for men
      overall and widespread disparity in methods used to capture exposure and report
      results. 

PMID- 24670373
TI  - Re: "Temporal relationship between uric acid concentration and risk of diabetes
      in a community-based study population".

PMID- 24670374
TI  - Two authors reply.

PMID- 24670375
TI  - Association between heme oxygenase 1 gene promoter polymorphisms and
      susceptibility to coronary artery disease: a HuGE review and meta-analysis.
AB  - We performed a systematic review and meta-analysis of heme oxygenase 1 gene (HO
      1) promoter polymorphisms and susceptibility to coronary artery disease (CAD)
      based on eligible studies retrieved from electronic databases from 2002 to 2013.
      Eleven studies, involving 10,170 patients with CAD and 6,868 controls, were
      included. Overall, no significantly decreased risk of CAD was found in persons
      with the SS genotype of the HO-1 (GT)n repeat length polymorphism compared with
      those with the LL + SL genotype. However, decreased risks of CAD were observed in
      the Asian subgroup, the coronary-artery-narrowing >=50% subgroup, the myocardial
      infarction subgroup, the age- and sex-matched subgroup, and the good-quality
      reports subgroup. The primary heterogeneity in the studies came from age and sex
      matching and the extent of coronary stenosis. CAD risk was significantly
      decreased for persons with the AA genotype of the T(-413)A single-nucleotide
      polymorphism versus those with the TT genotype, but most of the studies showed
      that the allele distribution was inconsistent with Hardy-Weinberg equilibrium. In
      this meta-analysis, we found that the (GT)n SS genotype was associated with
      decreased risk of CAD after controlling for biases due to age and sex matching,
      extent of coronary stenosis, ethnicity, and study quality. The relationship
      between the T(-413)A single-nucleotide polymorphism and CAD should be interpreted
      more cautiously. 

PMID- 24670376
TI  - Pretreatment with chemotherapeutics for enhanced nanoparticles accumulation in
      tumor: the potential role of G2 cycle retention effect.
AB  - Ligands were anchored onto nanoparticles (NPs) to improve the cell
      internalization and tumor localization of chemotherapeutics. However, the
      clinical application was shadowed by the complex preparation procedure and the
      immunogenicity and poor selectivity and stability of ligands. In this study, a
      novel strategy was developed to elevate the tumor cellular uptake and tumor
      localization of NPs utilizing the G2/M phase retention effect of docetaxel, one
      of the most common chemotherapeutics. Results showed pretreatment with docetaxel
      could effectively arrest cells in G2/M phase, leading to an enhanced cell uptake
      of NPs, which may be caused by the facilitated endocytosis of NPs. In vivo
      imaging and slice distribution also demonstrated the pretreatment with docetaxel
      improved the localization of NPs in tumor. This strategy can be easily
      transferred to clinical for cancer management. Combination chemotherapeutics
      injections with commercial nano-drugs may result in better antitumor effect than
      the administration of a single drug. 

PMID- 24670377
TI  - Temporary storage or permanent removal? The division of nitrogen between biotic
      assimilation and denitrification in stormwater biofiltration systems.
AB  - The long-term efficacy of stormwater treatment systems requires continuous
      pollutant removal without substantial re-release. Hence, the division of incoming
      pollutants between temporary and permanent removal pathways is fundamental. This
      is pertinent to nitrogen, a critical water body pollutant, which on a broad level
      may be assimilated by plants or microbes and temporarily stored, or transformed
      by bacteria to gaseous forms and permanently lost via denitrification.
      Biofiltration systems have demonstrated effective removal of nitrogen from urban
      stormwater runoff, but to date studies have been limited to a 'black-box'
      approach. The lack of understanding on internal nitrogen processes constrains
      future design and threatens the reliability of long-term system performance.
      While nitrogen processes have been thoroughly studied in other environments,
      including wastewater treatment wetlands, biofiltration systems differ
      fundamentally in design and the composition and hydrology of stormwater inflows,
      with intermittent inundation and prolonged dry periods. Two mesocosm experiments
      were conducted to investigate biofilter nitrogen processes using the stable
      isotope tracer 15NO3(-) (nitrate) over the course of one inflow event. The
      immediate partitioning of 15NO3(-) between biotic assimilation and
      denitrification were investigated for a range of different inflow concentrations
      and plant species. Assimilation was the primary fate for NO3(-) under typical
      stormwater concentrations (~1-2 mg N/L), contributing an average 89-99% of 15NO3(
      ) processing in biofilter columns containing the most effective plant species,
      while only 0-3% was denitrified and 0-8% remained in the pore water.
      Denitrification played a greater role for columns containing less effective
      species, processing up to 8% of 15NO3(-), and increased further with nitrate
      loading. This study uniquely applied isotope tracing to biofiltration systems and
      revealed the dominance of assimilation in stormwater biofilters. The findings
      raise important questions about nitrogen release upon plant senescence,
      seasonally and in the long term, which have implications on the management and
      design of biofiltration systems.

PMID- 24670378
TI  - Ambiguities in the LAST standardization project?

PMID- 24670379
TI  - Letter to the editor - reply.

PMID- 24670380
TI  - Developmental Validation of the ParaDNA(r) Screening System - A presumptive test
      for the detection of DNA on forensic evidence items.
AB  - Current assessment of whether a forensic evidence item should be submitted for
      STR profiling is largely based on the personal experience of the Crime Scene
      Investigator (CSI) and the submissions policy of the law enforcement authority
      involved. While there are chemical tests that can infer the presence of DNA
      through the detection of biological stains, the process remains mostly subjective
      and leads to many samples being submitted that give no profile or not being
      submitted although DNA is present. The ParaDNA((r)) Screening System was
      developed to address this issue. It consists of a sampling device, pre-loaded
      reaction plates and detection instrument. The test uses direct PCR with
      fluorescent HyBeaconTM detection of PCR amplicons to identify the presence and
      relative amount of DNA on an evidence item and also provides a gender
      identification result in approximately 75 minutes. This simple-to-use design
      allows objective data to be acquired by both DNA analyst and non-specialist
      personnel, to enable a more informed submission decision to be made. The
      developmental validation study described here tested the sensitivity,
      reproducibility, accuracy, inhibitor tolerance, and performance of the ParaDNA
      Screening System on a range of mock evidence items. The data collected
      demonstrates that the ParaDNA Screening System identifies the presence of DNA on
      a variety of evidence items including blood, saliva and touch DNA items.

PMID- 24670381
TI  - MiR-146a negatively regulates TLR2-induced inflammatory responses in
      keratinocytes.
AB  - Keratinocytes represent the first line of defense against pathogens in the skin
      and have important roles in initiating and regulating inflammation during
      infection and autoimmunity. Here we investigated the role of miR-146a in the
      regulation of the innate immune response of keratinocytes. Toll-like receptor 2
      (TLR2) stimulation of primary human keratinocytes resulted in an NF-kappaB- and
      mitogen-activated protein kinase-dependent upregulation of miR-146a expression,
      which was surprisingly long lasting, contrasting with the rapid and transient
      induction of inflammatory mediators. Overexpression of miR-146a significantly
      suppressed the production of IL-8, CCL20, and tumor necrosis factor-alpha, which
      functionally suppressed the chemotactic attraction of neutrophils by
      keratinocytes. Inhibition of endogenous miR-146a induced the production of
      inflammatory mediators even in nonstimulated keratinocytes, and potentiated the
      effect of TLR2 stimulation. Transcriptomic profiling revealed that miR-146a
      suppresses the expression of a large number of immune-related genes in
      keratinocytes. MiR-146a downregulated interleukin-1 receptor-associated kinase 1
      and TNF receptor-associated factor 6, two key adapter molecules downstream of TLR
      signaling, and suppressed NF-kappaB promoter-binding activity as shown by
      promoter luciferase experiments. Together, these data identify miR-146a as a
      regulatory element in keratinocyte innate immunity, which prevents the production
      of inflammatory mediators under homeostatic conditions and serves as a potent
      negative feedback regulator after TLR2 stimulation. 

PMID- 24670382
TI  - Changes in dermal fibroblasts from Abcc6(-/-) mice are present before and after
      the onset of ectopic tissue mineralization.
AB  - Pseudoxanthoma elasticum (PXE), a rare genetic disease caused by mutations in the
      ABCC6 gene, is characterized by progressive calcification of elastic fibers in
      the skin, eyes, and the cardiovascular system. The pathomechanism of the
      mineralization is still obscure. Several hypotheses have been proposed, one of
      them suggesting a role for fibroblasts in controlling the amount and the quality
      of the calcified extracellular matrix. This hypothesis raises the question
      whether changes in mesenchymal cells are the cause and/or the consequences of the
      calcification process. In this study, fibroblasts were isolated and cultured from
      Abcc6(+/+) and Abcc6(-/-) mice of different ages to investigate parameters known
      to be associated with the phenotype of fibroblasts from PXE patients. Results
      demonstrate that a few changes (Ank and Opn downregulation) are already present
      before the occurrence of calcification. By contrast, a modification of other
      parameters (intracellular O2- content, Tnap activity, and Bmp2 upregulation) can
      be observed in Abcc6(-/-) mice after the onset of tissue mineralization. These
      data suggest that in the Abcc6(-/-) genotype, dermal fibroblasts actively
      contribute to changes that promote matrix calcification and that these cells can
      be further modulated with time by the calcified environment, thus contributing to
      the age-dependent progression of the disease.

PMID- 24670383
TI  - siRNA-targeting transforming growth factor-beta type I receptor reduces wound
      scarring and extracellular matrix deposition of scar tissue.
AB  - Hypertrophic scarring is related to persistent activation of transforming growth
      factor-beta (TGF-beta)/Smad signaling. In the TGF-beta/Smad signaling cascade,
      the TGF-beta type I receptor (TGFBRI) phosphorylates Smad proteins to induce
      fibroblast proliferation and extracellular matrix deposition. In this study, we
      inhibited TGFBRI gene expression via TGFBRI small interfering RNA (siRNA) to
      reduce fibroblast proliferation and extracellular matrix deposition. Our results
      demonstrate that downregulating TGFBRI expression in cultured human hypertrophic
      scar fibroblasts significantly suppressed cell proliferation and reduced type I
      collagen, type III collagen, fibronectin, and connective tissue growth factor
      (CTGF) mRNA, and type I collagen and fibronectin protein expression. In addition,
      we applied TGFBRI siRNA to wound granulation tissue in a rabbit model of
      hypertrophic scarring. Downregulating TGFBRI expression reduced wound scarring,
      the extracellular matrix deposition of scar tissue, and decreased CTGF and alpha
      smooth muscle actin mRNA expression in vivo. These results suggest that TGFBRI
      siRNA could be applied clinically to prevent hypertrophic scarring. 

PMID- 24670384
TI  - The nano-scale mechanical properties of the extracellular matrix regulate dermal
      fibroblast function.
AB  - Changes in the mechanical properties of dermis occur during skin aging or tissue
      remodeling and affect the activity of resident fibroblasts. With the aim to
      establish elastic culture substrates that reproduce the variable softness of
      dermis, we determined Young's elastic modulus E of human dermis at the cell
      perception level using atomic force microscopy. The E of dermis ranged from 0.1
      to 10 kPa, varied depending on body area and dermal layer, and tended to increase
      with age in 26-55-year-old donors. The activation state of human dermal
      fibroblasts cultured on "skin-soft" E (5 kPa) silicone culture substrates was
      compared with stiff plastic culture (GPa), collagen gel cultures (0.1-9 kPa), and
      fresh human dermal tissue. Fibroblasts cultured on skin-soft silicones displayed
      low mRNA levels of fibrosis-associated genes and increased expression of the
      matrix metalloproteinases (MMPs) MMP-1 and MMP-3 as compared with collagen gel
      and plastic cultures. The activation profile exhibited by fibroblasts on "skin
      soft" silicone culture substrates was most comparable with that of human dermis
      than any other tested culture condition. Hence, providing biomimetic mechanical
      conditions generates fibroblasts that are more suitable to investigate
      physiologically relevant cell processes than fibroblasts spontaneously activated
      by stiff conventional culture surfaces. 

PMID- 24670385
TI  - Maternal genetic variation accounts in part for the associations of maternal size
      during pregnancy with offspring cardiometabolic risk in adulthood.
AB  - BACKGROUND: Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight
      gain (GWG) are associated with cardiometabolic risk (CMR) traits in the
      offspring. The extent to which maternal genetic variation accounts for these
      associations is unknown. METHODS/RESULTS: In 1249 mother-offspring pairs
      recruited from the Jerusalem Perinatal Study, we used archival data to
      characterize ppBMI and GWG and follow-up data from offspring to assess CMR,
      including body mass index (BMI), waist circumference, glucose, insulin, blood
      pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores
      (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each
      CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs)
      characterizing variation in 170 candidate genes potentially related to fetal
      development and/or metabolic risk. We fit linear regression models to examine the
      associations of ppBMI and GWG with CMR traits with and without adjustment for
      GRS. Compared to unadjusted models, the coefficient for the association of a one
      standard-deviation (SD) difference in GWG and offspring BMI decreased by 41%
      (95%CI -81%, -11%) from 0.847 to 0.503 and the coefficient for a 1SD difference
      in GWG and WC decreased by 63% (95%CI -318%, -11%) from 1.196 to 0.443. For other
      traits, there were no statistically significant changes in the coefficients for
      GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits
      were significantly altered by adjustment for GRS. CONCLUSIONS: Maternal genetic
      variation may account in part for associations of GWG with offspring BMI and WC
      in young adults.

PMID- 24670386
TI  - Development and implementation of South Asia's first heat-health action plan in
      Ahmedabad (Gujarat, India).
AB  - Recurrent heat waves, already a concern in rapidly growing and urbanizing South
      Asia, will very likely worsen in a warming world. Coordinated adaptation efforts
      can reduce heat's adverse health impacts, however. To address this concern in
      Ahmedabad (Gujarat, India), a coalition has been formed to develop an evidence
      based heat preparedness plan and early warning system. This paper describes the
      group and initial steps in the plan's development and implementation. Evidence
      accumulation included extensive literature review, analysis of local temperature
      and mortality data, surveys with heat-vulnerable populations, focus groups with
      health care professionals, and expert consultation. The findings and
      recommendations were encapsulated in policy briefs for key government agencies,
      health care professionals, outdoor workers, and slum communities, and synthesized
      in the heat preparedness plan. A 7-day probabilistic weather forecast was also
      developed and is used to trigger the plan in advance of dangerous heat waves. The
      pilot plan was implemented in 2013, and public outreach was done through training
      workshops, hoardings/billboards, pamphlets, and print advertisements. Evaluation
      activities and continuous improvement efforts are ongoing, along with plans to
      explore the program's scalability to other Indian cities, as Ahmedabad is the
      first South Asian city to address heat-health threats comprehensively. 

PMID- 24670387
TI  - Exposure to an environmentally relevant mixture of brominated flame retardants
      affects fetal development in Sprague-Dawley rats.
AB  - Brominated flame retardants are incorporated into a wide variety of consumer
      products and are known to enter into the surrounding environment, leading to
      human exposure. There is accumulating evidence that these compounds have adverse
      effects on reproduction and development in humans and animal models. Animal
      studies have generally characterized the outcome of exposure to a single
      technical mixture or congener. Here, we determined the impact of exposure of rats
      prior to mating and during gestation to a mixture representative of congener
      levels found in North American household dust. Adult female Sprague-Dawley rats
      were fed a diet containing 0, 0.75, 250 or 750mg/kg of a mixture of flame
      retardants (polybrominated diphenyl ethers, hexabromocyclododecane) from two
      weeks prior to mating to gestation day 20. This formulation delivered nominal
      doses of 0, 0.06, 20 and 60mg/kg body weight/day. The lowest dose approximates
      high human exposures based on house dust levels and the dust ingestion rates of
      toddlers. Litter size and resorption sites were counted and fetal development
      evaluated. No effects on maternal health, litter size, fetal viability, weights,
      crown rump lengths or sex ratios were detected. The proportion of litters with
      fetuses with anomalies of the digits (soft tissue syndactyly or malposition of
      the distal phalanges) was increased significantly in the low (0.06mg/kg/day) dose
      group. Skeletal analysis revealed a decreased ossification of the sixth sternebra
      at all exposure levels. Thus, exposure to an environmentally relevant mixture of
      brominated flame retardants results in developmental abnormalities in the absence
      of apparent maternal toxicity. The relevance of these findings for predicting
      human risk is yet to be determined. 

PMID- 24670388
TI  - Physiologically based pharmacokinetic modeling framework for quantitative
      prediction of an herb-drug interaction.
AB  - Herb-drug interaction predictions remain challenging. Physiologically based
      pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of
      potential herb-drug interactions using the semipurified milk thistle preparation,
      silibinin, as an exemplar herbal product. Interactions between silibinin
      constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A)
      were simulated. A low silibinin dose (160 mg/day * 14 days) was predicted to
      increase midazolam area under the curve (AUC) by 1%, which was corroborated with
      external data; a higher dose (1,650 mg/day * 7 days) was predicted to increase
      midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept
      clinical study confirmed minimal interaction between high-dose silibinin and both
      midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively).
      Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be
      clinically important. Application of this PBPK modeling framework to other herb
      drug interactions could facilitate development of guidelines for quantitative
      prediction of clinically relevant interactions.CPT Pharmacometrics Syst.
      Pharmacol. (2014) 3, e107; doi:10.1038/psp.2013.69; advance online publication 26
      March 2014. 

PMID- 24670390
TI  - Rapamycin in preventive (very low) doses.

PMID- 24670389
TI  - Noncanonical Wnt5a enhances Wnt/beta-catenin signaling during osteoblastogenesis.
AB  - Wnt regulates bone formation through beta-catenin-dependent canonical and 
      independent noncanonical signaling pathways. However, the cooperation that exists
      between the two signaling pathways during osteoblastogenesis remains to be
      elucidated. Here, we showed that the lack of Wnt5a in osteoblast-lineage cells
      impaired Wnt/beta-catenin signaling due to the reduced expression of Lrp5 and
      Lrp6. Pretreatment of ST2 cells, a stromal cell line, with Wnt5a enhanced
      canonical Wnt ligand-induced Tcf/Lef transcription activity. Short hairpin RNA
      mediated knockdown of Wnt5a, but not treatment with Dkk1, an antagonist of
      Wnt/beta-catenin signaling, reduced the expression of Lrp5 and Lrp6 in osteoblast
      lineage cells under osteogenic culture conditions. Osteoblast-lineage cells from
      Wnt5a-deficient mice exhibited reduced Wnt/beta-catenin signaling, which impaired
      osteoblast differentiation and enhanced adipocyte differentiation. Adenovirus
      mediated gene transfer of Lrp5 into Wnt5a-deficient osteoblast-lineage cells
      rescued their phenotypic features. Therefore, Wnt5a-induced noncanonical
      signaling cooperates with Wnt/beta-catenin signaling to achieve proper bone
      formation. 

PMID- 24670391
TI  - Adjunctive drug therapies for treatment of respiratory diseases in the newborn:
      based on evidence or habit?
AB  - Respiratory distress syndrome is a disease of prematurity and is caused by a
      relative deficiency of endogenous surfactant production. Respiratory distress
      syndrome is the most common cause of mortality and morbidity in the newborn
      population and the standard of care is to provide exogenous surfactant therapy.
      This saves lives and reduces respiratory complications but, despite treatment, a
      significant proportion of these infants go onto develop chronic lung disease, the
      severest form of which is bronchopulmonary dysplasia. Once developed, this is a
      multisystem disease and treatment is mostly supportive by using various
      therapeutic adjuncts. Some of these have been proven to be safe and effective in
      large randomized, controlled trials but similar evidence for other drugs is
      lacking. The aim of this paper is to provide an overview and critically appraise
      the available scientific evidence for or against their use in routine practice. 

PMID- 24670392
TI  - The use of high-flow nasal oxygen therapy in the management of hypercarbic
      respiratory failure.
AB  - Hypercarbic respiratory failure, occurring secondary to chronic lung disease, is
      a frequently encountered problem. These patients present a significant challenge
      to respiratory and critical care services, as many are unsuitable for mechanical
      ventilation and most have multiple comorbidities. Recently, noninvasive
      ventilation (NIV) has become established as the primary modality for respiratory
      support in this group of patients. Several factors limit patient compliance with
      NIV, not least comfort and tolerability. A recent innovation in adult critical
      care is the use of high-flow nasal oxygen (HFNO) devices. These systems are
      capable of delivering high gas flows via nasal cannulae, with the ability to
      blend air and oxygen to give a controlled FiO2. Few clinical studies have been
      conducted in adults, although several are planned. To date the majority of
      available evidence addresses the use of HFNO in hypoxemic respiratory failure.
      Here we present a case in which a HFNO system was used to successfully manage
      hypercarbic respiratory failure in a patient unable to tolerate conventional NIV.

PMID- 24670393
TI  - Highly conductive and low cost Ni-PET flexible substrate for efficient dye
      sensitized solar cells.
AB  - The highly conductive and flexible nickel-polyethylene terephthalate (Ni-PET)
      substrate was prepared by a facile way including electrodeposition and hot-press
      transferring. The effectiveness was demonstrated in the counter electrode of dye
      sensitized solar cells (DSSCs). The Ni film electrodeposition mechanism,
      microstructure, and DSSC performance for the Ni-PET flexible substrate were
      investigated. The uniform and continuous Ni film was first fabricated by
      electroplating metallic Ni on fluorine-doped tin oxide (FTO) and then intactly
      transferred onto PET via hot-pressing using Surlyn as the joint adhesive. The
      obtained flexible Ni-PET substrate shows low sheet resistance of 0.18Omega/? and
      good chemical stability for the I(-)/I(3-) electrolyte. A high light-to-electric
      energy conversion efficiency of 7.89% was demonstrated in DSSCs system based on
      this flexible electrode substrate due to its high conductivity, which presents an
      improvement of 10.4% as compared with the general ITO-PEN flexible substrate.
      This method paves a facile and cost-effective way to manufacture various metals
      on a plastic nonconducive substrate beneficial for the devices toward flexible
      and rollable. 

PMID- 24670394
TI  - Misdiagnosis of an extragastrointestinal stromal tumor in the rectovaginal
      septum.
AB  - INTRODUCTION: Gastrointestinal stromal tumors are very rare, representing 0.1% to
      1% of gastrointestinal malignancies. Gastrointestinal stromal tumors outside the
      digestive tract comprise a very small fraction of all gastrointestinal stromal
      tumors, and their most common locations are the omentum, the mesentery, and, in
      few cases, the rectovaginal septum. Despite their low incidence,
      extragastrointestinal stromal tumors are potentially malignant tumors and they
      present a high rate of recurrences. This, added to the fact that they are often
      asymptomatic until advanced stages, determines an unfavorable prognosis. CASE
      REPORT: We report a case of gastrointestinal stromal tumor located in the
      rectovaginal septum, which recurred after local excision; hence, a reintervention
      was needed. CONCLUSIONS: A correct differential diagnosis between
      extragastrointestinal stromal tumors and other similar pathologies such as
      leiomyomas or schwannomas is imperative based on their histology and
      immunohistochemistry. The correct diagnosis of extragastrointestinal stromal
      tumors allows to start adequate treatment and follow-up, preventing recurrence
      that determines their poor prognosis.

PMID- 24670395
TI  - Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion
      at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from
      cognitively normal elderly adults.
AB  - BACKGROUND: Structural magnetic resonance imaging has been employed for
      evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD).
      Arterial spin labeling (ASL) technique could detect cerebral perfusion
      abnormalities in AD. OBJECTIVE: We hypothesized that combination of hippocampal
      volumetry and cerebral blood flow yield higher accuracy than either method alone
      in discriminating AD patients from cognitively normal elderly adults. MATERIALS
      AND METHODS: 13 AD patients and 15 healthy controls were studied using a 3-tesla
      scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences
      were employed for cerebral volumetry and perfusion respectively. Manual Right and
      left hippocampal volumetry was performed manually by ANALYZE software, with total
      intracranial volume normalization. ASL data were analyzed by institutional
      specially-design software to calculate cerebral blood flow of region-of-interests
      placed at the middle and posterior cingulate gyri. RESULTS: Right and left
      hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows
      were significantly lower in the patients than in the controls (independent
      samples t-tests, p < 0.05), and prediction accuracies of 89.3%, 82.1%, 75.0% and
      71.4% were achieved for each of the above parameters, respectively. In
      distinguishing patients from controls using corresponding optimized cut-off
      values, various combinations of these parameters were used to create the Receiver
      Operating Characteristic curves. The highest area under curve value was 0.944, by
      combining cerebral blood flow at the middle cingulate gyrus, normalized right and
      left hippocampal volumes. CONCLUSIONS: A 'one-stop-shop' magnetic resonance study
      of combined hippocampal volumetry and cerebral perfusion has improved efficacy in
      discriminating AD patients from cognitively normal elderly adults.

PMID- 24670396
TI  - Dynamic cerebral autoregulation and tissue oxygenation in amnestic mild cognitive
      impairment.
AB  - BACKGROUND: Vascular disease and dysfunction are associated with the higher risk
      of Alzheimer's disease hypothetically due to cerebral hypoperfusion. Brain
      perfusion is protected by cerebral autoregulation, which, under normal
      conditions, maintains a constant cerebral blood flow and brain tissue
      oxygenation. OBJECTIVE: To determine whether dynamic regulation of cerebral blood
      flow and tissue oxygenation is impaired in patients with amnestic mild cognitive
      impairment (aMCI). METHODS: Twenty-seven patients with aMCI and 15 control
      subjects with normal cognitive function underwent the measurements of cerebral
      hemodynamics, brain MR imaging, and neurocognitive assessment. Dynamic regulation
      of cerebral blood flow and tissue oxygenation were assessed by transfer function
      analysis of changes in mean blood pressure (MBP), normalized cerebral blood flow
      velocity (CBFV%), and cerebral tissue oxygenation index (TOI) at baseline and
      during a sit-stand maneuver. RESULTS: Patients with aMCI demonstrated lower
      cognitive performance in memory and executive function, accompanied by smaller
      entorhinal cortex volumes. At baseline, cerebral TOI was lower in patients with
      aMCI than in control subjects. Lower cerebral TOI was also correlated with lower
      cognitive performance in memory and executive function in all subjects. Transfer
      function gain and phase between MBP and CBFV% and between CBFV% and cerebral TOI
      were not different between the groups. Within aMCI patients, greater oscillations
      of cerebral TOI and higher transfer function gain between cerebral TOI and CBFV%
      were associated with the lower scores on delayed recall. CONCLUSION: Dynamic
      regulation of cerebral tissue oxygenation is associated with neurocognitive
      dysfunction in aMCI patients.

PMID- 24670397
TI  - Interactions between amyloid-beta and tau in cerebrospinal fluid of people with
      mild cognitive impairment and Alzheimer's disease.
AB  - BACKGROUND: Despite the physiological sequestration of amyloid-beta (Abeta)
      peptides by various carriers, interactions between peptides and protein tau
      appear to be pathological and involved in the development of Alzheimer's disease
      (AD). A recent study reported increased Abeta-tau interactions in the neurons of
      AD patients. OBJECTIVE: We investigated the possibility that levels of Abeta-tau
      complexes in cerebrospinal fluid could be a prospective biomarker of AD, with
      greater sensitivity and specificity than Abeta1-42, tau, or phospho-tau
      individually. METHODS: By means of ELISA, we estimated levels of the complexes in
      161 people (non-demented controls, people with mild cognitive impairment (MCI),
      probable AD or other types of dementia). RESULTS: We found significant reductions
      in levels in people with MCI due to AD (down to 84.5%) or with AD (down to 80.5%)
      but not in other types of dementia. The sensitivity of the new biomarker to AD
      was 68.6%, the specificity 73.3% (compared to controls) or 59.1-66.1% (compared
      to other types of dementia). No significant correlations were observed between
      the complexes and the remaining biomarkers or between those and Mini-Mental State
      Examination score. CONCLUSION: We suppose that attenuated levels of complexes in
      cerebrospinal fluid reflect the accumulation of Abeta bound to tau in AD neurons
      and that changes start many years before symptom onset, analogously to those in
      Abeta1-42, tau, or phospho-tau. Unfortunately, these complexes are not a
      significantly better biomarker of AD than current biomarkers.

PMID- 24670398
TI  - Glutamatergic dysfunctioning in Alzheimer's disease and related therapeutic
      targets.
AB  - The impairment of glutamatergic neurotransmission plays an important role in the
      development of Alzheimer's disease (AD). The pathological process, which involves
      the production of amyloid-beta peptides and hyperphosphorylated tau proteins,
      spreads over well-delineated neuroanatomical circuits. The gradual deterioration
      of proper synaptic functioning (via GluN2A-containing N-methyl-D-aspartate
      receptors, NMDARs) and the development of excitotoxicity (via GluN2B-containing
      NMDARs) in these structures both accompany the disease pathogenesis. Although one
      of the most important therapeutic targets would be glutamate excitotoxicity, the
      application of conventional anti-glutamatergic agents could result in further
      deterioration of synaptic transmission and intolerable side-effects. With regard
      to NMDAR antagonists with tolerable side-effects, ion channel blockers with low
      affinity, glycine site agents, and specific antagonists of polyamine site and
      GluN2B subunit may come into play. However, in the mirror of experimental data,
      only the application of ion channel blockers with pronounced voltage dependency,
      low affinity, and rapid unblocking kinetics (e.g., memantine) and specific
      antagonists of the GluN2B subunit (e.g., ifenprodil and certain kynurenic acid
      amides) resulted in desirable symptom amelioration. Therefore we propose that
      these kinds of chemical agents may have therapeutic potential for present and
      future drug development. 

PMID- 24670399
TI  - Neuropsychological correlates of hippocampal atrophy in memory testing in
      nondemented older adults.
AB  - BACKGROUND AND OBJECTIVE: Cognitive deficits in older adults attributable to
      Alzheimer's disease (AD) pathology are featured early on by hippocampal
      impairment. Among tests used to evaluate memory, verbal memory tests with
      controlled encoding and cued recall are believed to be specific for hippocampal
      impairment. The objective of this study was to assess the relation between left
      and right hippocampal volumes and several frequently used memory tests. METHODS:
      Fifty six nondemented older adults (30 with amnestic mild cognitive impairment
      and 26 cognitively healthy older adults) underwent neuropsychological testing
      including: (1) The Enhanced Cued Recall test (ECR), a memory test with controlled
      encoding and recall; (2) the Auditory Verbal Learning Test (AVLT), a verbal
      memory test without controlled encoding and with delayed recall; and (3) The Rey
      Osterrieth Complex Figure test (ROCF), a visuospatial memory test-recall
      condition. 1.5T brain MRI scans were used to measure estimated total intracranial
      volume (eTIV) along with hippocampal right and left volumes, which were measured
      with quantitative volumetry using FreeSurfer package (version 4.4.0). Spearman
      partial correlation controlled for age was used to correct for non-normal score
      distribution and effect of age. RESULTS: We found moderate correlations of
      hippocampal volumes with AVLT 1-5 scores, AVLT delayed recall, ECR free and total
      recall, and ROCF reproduction. Total recall in ECR using cued recall was not
      superior to any of the free recall tests. No correlation in any memory test was
      achieved with eTIV. CONCLUSION: Verbal memory tests, either with controlled
      encoding and cued delayed recall (ECR), or without it (AVLT), as well as
      nonverbal memory test with delayed recall (ROCF), equally reflect hippocampal
      atrophy in nondemented older adults.

PMID- 24670401
TI  - Diverse vascular lesions in systemic lupus erythematosus and clinical
      implications.
AB  - PURPOSE OF REVIEW: Vascular injury is one of the typical symptoms of systemic
      lupus erythematosus (SLE), and may play a key role in the choice of treatment
      strategy and prediction of prognosis. In this review, diverse vascular lesions in
      SLE and their clinical significance are discussed. RECENT FINDINGS: The clinical
      features of vascular disease in SLE differ from organ to organ, and may be
      extreme with regard to renal vascular lesions. Vascular lesions in SLE may be of
      inflammatory or thrombotic origin, and immune system dysfunction is considered to
      be a predominant feature. Numerous lines of evidence suggest that the activation
      and injury of endothelial cells might play a key role in the pathogenesis.
      SUMMARY: Vascular lesions in SLE are mediated by a complex interaction between
      the immune system and other contributing factors. Different therapies developed
      for vascular lesions, both immunosuppressive and nonimmunosuppressive, should be
      selected based on the different clinical and pathological characteristics, and
      our future understanding of the different mechanisms involved.

PMID- 24670402
TI  - Estimating and measuring glomerular filtration rate: methods of measurement and
      markers for estimation.
AB  - PURPOSE OF REVIEW: Glomerular filtration rate (GFR) is the best overall measure
      of kidney function. Reference GFR measurements (e.g. inulin clearance) are
      laborious. Estimation of GFR using equations based on endogenous filtration
      markers is simpler, cheaper and easy to apply in practice but suffers from
      limited accuracy and reproducibility. This review summarizes the recent studies
      comparing measured and estimated GFR in various populations and disease settings.
      We consider the utility of newer estimating equations based on standardized
      methodology, including those incorporating cystatin C. RECENT FINDINGS: Equations
      proposed by the Chronic Kidney Disease-Epidemiology (CKD-EPI) Consortium slightly
      improve the accuracy of GFR estimation compared with those used formerly. The
      black ethnicity coefficient in the CKD-EPI equation may not be transferable
      across other black populations and the equations require further validation in
      other ethnic groups. All currently reported equations fall short of ideal.
      Incorporation of cystatin C into the CKD-EPI equation improves precision and
      offers hope of a GFR estimate that may not require ethnic adjustment. SUMMARY:
      The ideal biomarker and equation to estimate GFR would provide reproducible and
      accurate results across the entire range of GFRs, populations and diseases. Newer
      GFR markers and equations are required to fulfil this holy grail of research.

PMID- 24670400
TI  - Amyloidosis associated with cerebral amyloid angiopathy: cell signaling pathways
      elicited in cerebral endothelial cells.
AB  - Substantial genetic, biochemical, and in vivo data indicate that progressive
      accumulation of amyloid-beta (Abeta) plays a central role in the pathogenesis of
      Alzheimer's disease (AD). Historically centered in the importance of parenchymal
      plaques, the role of cerebral amyloid angiopathy (CAA)--a frequently neglected
      amyloid deposit present in >80% of AD cases--for the mechanism of disease
      pathogenesis is now starting to emerge. CAA consistently associates with
      microvascular modifications, ischemic lesions, micro- and macro-hemorrhages, and
      dementia, progressively affecting cerebral blood flow, altering blood-brain
      barrier permeability, interfering with brain clearance mechanisms and triggering
      a cascade of deleterious pro-inflammatory and metabolic events that compromise
      the integrity of the neurovascular unit. New evidence highlights the contribution
      of pre-fibrillar Abeta in the induction of cerebral endothelial cell dysfunction.
      The recently discovered interaction of oligomeric Abeta species with TRAIL DR4
      and DR5 cell surface death receptors mediates the engagement of mitochondrial
      pathways and sequential activation of multiple caspases, eliciting a cascade of
      cell death mechanisms while unveiling an opportunity for exploring mechanistic
      based therapeutic interventions to preserve the integrity of the neurovascular
      unit.

PMID- 24670403
TI  - Strategies for planning the optimal dialysis access for an individual patient.
AB  - PURPOSE OF REVIEW: Achieving functioning vascular access in hemodialysis patients
      remains challenging. Current guidelines recommend creating arteriovenous fistulas
      (AVFs) as the initial form of vascular access and are primarily based on
      outdated, observational data. Determining the optimal access for each individual
      patient is, therefore, of great interest. RECENT FINDINGS: Multiple recent
      studies suggest that certain subgroups of patients may benefit from alternative
      forms of vascular access. In particular, the elderly and patients with limited
      life-expectancy may be less likely to benefit from an AVF first approach. These
      patients may be more likely to die before benefiting from an AVF and are more
      likely to experience primary failure of an AVF. If these factors are considered,
      arteriovenous grafts, and in some cases central venous catheters, become a valid
      alternative form of vascular access. Patients may also have strong opinions about
      each type of vascular access, leading to a preference for alternative forms of
      access. SUMMARY: A patient-centered approach to the choice of dialysis access
      that incorporates a balance between recent evidence from the literature and
      patient preferences may be preferred to the current fistula first focus in
      vascular access choice.

PMID- 24670404
TI  - Safety of medical therapy in patients with chronic kidney disease and end-stage
      renal disease.
AB  - PURPOSE OF REVIEW: Maintaining patient safety is a necessary step to improve
      healthcare delivery. Patients with chronic kidney disease (CKD) and end-stage
      renal disease (ESRD) have an increased frequency of adverse safety events largely
      because of medication errors. RECENT FINDINGS: CKD and ESRD have several features
      which threaten patient safety. Reduced glomerular filtration rate affects the
      clearance of many medications and is also associated with several comorbidities
      such as diabetes, cardiovascular disease, metabolic bone disease, and anemia.
      These comorbidities of CKD often increase the complexity of treatment regimens.
      Patients with ESRD, requiring dialysis or transplantation, have an even greater
      potential for adverse safety events because of the reliance on renal replacement
      modalities and the frequent requirements of polypharmacy and potential drug-drug
      interactions. SUMMARY: There is an important need to develop strategies to
      provide inpatient and outpatient management plans to limit the risk of adverse
      medication errors across a wide range of educational and socioeconomic
      backgrounds, and a critical need to develop a uniform set of standards for
      evaluating patient safety in CKD and ESRD as well as appropriate descriptions of
      the prototypical safety profiles of patients who have CKD, a kidney transplant,
      or who are on dialysis.

PMID- 24670405
TI  - Mechanisms of lower maintenance dose of tacrolimus in obese patients.
AB  - A retrospective analysis suggested that blood tacrolimus concentrations were
      consistent among patients with a body mass index (BMI) that was lean (<18.5),
      normal (>= 18.5 and <25) or overweight/obese (>= 25). The average maintenance
      dose of tacrolimus in patients with BMI >= 25 was significantly lower compared
      with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed
      a normal diet were given tacrolimus intravenously or orally. The blood
      concentrations of tacrolimus in obese rats were significantly higher than those
      in lean rats after administration via both routes. The moment analysis has
      suggested that CLtot and Vdss of tacrolimus were not significantly different
      between lean and obese rats. The bioavailability was higher in obese rats,
      compared with that in lean rats. The protein expression of Cyp3a2 in the liver
      was significantly decreased in obese rats, compared with lean rats, while P-gp in
      the small intestine was also significantly decreased in obese rats. These results
      suggested that the steady-state trough concentration of tacrolimus in obese
      patients was well maintained by a relatively low dose compared with that in
      normal and lean patients, presumably due to increased bioavailability.

PMID- 24670407
TI  - Trail communication regulated by two trail pheromone components in the fungus
      growing termite Odontotermes formosanus (Shiraki).
AB  - The eusocial termites are well accomplished in chemical communication, but how
      they achieve the communication using trace amount of no more than two pheromone
      components is mostly unknown. In this study, the foraging process and trail
      pheromones of the fungus-growing termite Odontotermes formosanus (Shiraki) were
      systematically studied and monitored in real-time using a combination of
      techniques, including video analysis, solid-phase microextraction, gas
      chromatography coupled with either mass spectrometry or an electroantennographic
      detector, and bioassays. The trail pheromone components in foraging workers were
      (3Z)-dodec-3-en-1-ol and (3Z,6Z)-dodeca-3,6-dien-1-ol secreted by their sternal
      glands. Interestingly, ratio of the two components changed according to the
      behaviors that the termites were displaying. This situation only occurs in
      termites whereas ratios of pheromone components are fixed and species-specific
      for other insect cuticular glands. Moreover, in bioassays, the active thresholds
      of the two components ranged from 1 fg/cm to 10 pg/cm according to the behavioral
      contexts or the pheromonal exposure of tested workers. The two components did not
      act in synergy. (3Z)-Dodec-3-en-1-ol induced orientation behavior of termites
      that explore their environment, whereas (3Z,6Z)-dodeca-3,6-dien-1-ol had both an
      orientation effect and a recruitment effect when food was discovered. The trail
      pheromone of O. formosanus was regulated both quantitatively by the increasing
      number of workers involved in the early phases of foraging process, and
      qualitatively by the change in ratio of the two pheromone components on sternal
      glandular cuticle in the food-collecting workers. In bioassays, the responses of
      workers to the pheromone were also affected by the variation in pheromone
      concentration and component ratio in the microenvironment. Thus, this termite
      could exchange more information with nestmates using the traces of the two trail
      pheromone components that can be easily regulated within a limited
      microenvironment formed by the tunnels or chambers. 

PMID- 24670408
TI  - Short-chain flavor ester synthesis in organic media by an E. coli whole-cell
      biocatalyst expressing a newly characterized heterologous lipase.
AB  - Short-chain aliphatic esters are small volatile molecules that produce fruity and
      pleasant aromas and flavors. Most of these esters are artificially produced or
      extracted from natural sources at high cost. It is, however, possible to
      'naturally' produce these molecules using biocatalysts such as lipases and
      esterases. A gene coding for a newly uncovered lipase was isolated from a
      previous metagenomic study and cloned into E. coli BL21 (DE3) for overexpression
      using the pET16b plasmid. Using this recombinant strain as a whole-cell
      biocatalyst, short chain esters were efficiently synthesized by
      transesterification and esterification reactions in organic media. The
      recombinant lipase (LipIAF5-2) showed good affinity toward glyceryl trioctanoate
      and the highest conversion yields were obtained for the transesterification of
      glyceryl triacetate with methanol. Using a simple cetyl-trimethylammonium bromide
      pretreatment increased the synthetic activity by a six-fold factor and the whole
      cell biocatalyst showed the highest activity at 40 degrees C with a relatively
      high water content of 10% (w/w). The whole-cell biocatalyst showed excellent
      tolerance to alcohol and short-chain fatty acid denaturation. Substrate affinity
      was equally effective with all primary alcohols tested as acyl acceptors, with a
      slight preference for methanol. The best transesterification conversion of 50
      mmol glyceryl triacetate into isoamyl acetate (banana fragrance) provided near
      100% yield after 24 hours using 10% biocatalyst loading (w/w) in a fluidized bed
      reactor, allowing recycling of the biocatalyst up to five times. These results
      show promising potential for an industrial approach aimed at the biosynthesis of
      short-chain esters, namely for natural flavor and fragrance production in micro
      aqueous media. 

PMID- 24670409
TI  - Matrix metalloproteinase-9 deficiency attenuates diabetic nephropathy by
      modulation of podocyte functions and dedifferentiation.
AB  - Diabetic nephropathy is characterized by excessive deposition of extracellular
      matrix protein and disruption of the glomerular filtration barrier. Matrix
      metalloproteinases (MMPs) affect the breakdown and turnover of extracellular
      matrix protein, suggesting that altered expression of MMPs may contribute to
      diabetic nephropathy. Here we used an MMP-9 gene knockout mouse model, with in
      vitro experiments and clinical samples, to determine the possible role of MMP-9
      in diabetic nephropathy. After 6 months of streptozotocin-induced diabetes, mice
      developed markedly increased albuminuria, glomerular and kidney hypertrophy, and
      thickening of the glomerular basement membrane. Gelatin zymographic analysis and
      western blotting showed that there was enhanced MMP-9 protein production and
      activity in the glomeruli. However, MMP-9 knockout in diabetic mice significantly
      attenuated these nephropathy changes. In cultured podocytes, various cytokines
      related to diabetic nephropathy including TGF-beta1, TNF-alpha, and VEGF
      stimulated MMP-9 secretion. Overexpression of endogenous MMP-9 induced podocyte
      dedifferentiation. MMP-9 also interrupted podocyte cell integrity, promoted
      podocyte monolayer permeability to albumin, and extracellular matrix protein
      synthesis. In diabetic patients, the upregulation of urinary MMP-9 concentrations
      occurred earlier than the onset of microalbuminuria. Thus, MMP-9 seems to play a
      role in the development of diabetic nephropathy. 

PMID- 24670410
TI  - Renal fibrosis is the common feature of autosomal dominant tubulointerstitial
      kidney diseases caused by mutations in mucin 1 or uromodulin.
AB  - For decades, ill-defined autosomal dominant renal diseases have been reported,
      which originate from tubular cells and lead to tubular atrophy and interstitial
      fibrosis. These diseases are clinically indistinguishable, but caused by
      mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently
      described, MUC1. Affected family members show renal fibrosis in the biopsy and
      gradually declining renal function, with renal failure usually occurring between
      the third and sixth decade of life. Here we describe 10 families and define
      eligibility criteria to consider this type of inherited disease, as well as
      propose a practicable approach for diagnosis. In contrast to what the frequently
      used term 'Medullary Cystic Kidney Disease' implies, development of (medullary)
      cysts is neither an early nor a typical feature, as determined by MRI. In
      addition to Sanger and gene panel sequencing of the four genes, we established
      SNaPshot minisequencing for the predescribed cytosine duplication within a
      distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of
      9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On
      the basis of clinical and pathological characteristics we propose the term
      'Autosomal Dominant Tubulointerstitial Kidney Disease' as an improved
      terminology. This should enhance recognition and correct diagnosis of affected
      individuals, facilitate genetic counseling, and stimulate research into the
      underlying pathophysiology. 

PMID- 24670411
TI  - Increased intragraft rejection-associated gene transcripts in patients with donor
      specific antibodies and normal biopsies.
AB  - We investigated why some donor-specific antibody-positive patients do not develop
      antibody-mediated rejection. Of 71 donor-specific antibody-positive patients, 46
      had diagnosis of antibody-mediated rejection and 25 had normal biopsies. Fifty
      donor-specific antibody-negative patients with normal biopsies were used as a
      control group. A subgroup of 61 patients with available biopsy and 64 with blood
      samples were analyzed by microarrays. Both donor-specific antibody
      positive/antibody-mediated rejection-positive and negative biopsies showed
      increased expression of gene transcripts associated with cytotoxic T cells,
      natural killer cells, macrophages, interferon-gamma, and rejection compared to
      donor-specific antibody-negative biopsies. Regulatory T-cell transcripts were
      upregulated in donor-specific antibody-positive/antibody-mediated rejection
      positive and B-cell transcripts in donor-specific antibody-positive/antibody
      mediated rejection-negative biopsies. Whole-blood gene expression analysis showed
      increased immune activity in only donor-specific antibody-positive/antibody
      mediated rejection-positive but not negative patients. During a median follow-up
      of 36 months, 4 donor-specific antibody-positive/antibody-mediated rejection
      negative patients developed antibody-mediated rejection, 12 continued to have
      donor-specific antibody, but 9 lost their donor-specific antibody. Gene
      expression profiles did not predict the development of antibody-mediated
      rejection or the persistence of donor-specific antibody. Thus, donor-specific
      antibody-positive/antibody-mediated rejection-negative patients had increased
      rejection-associated gene transcripts in their allografts despite no histologic
      findings of rejection but not in their blood. This was found in both biopsy and
      blood samples of donor-specific antibody-positive/antibody-mediated rejection
      positive patients. 

PMID- 24670412
TI  - Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice.
AB  - ErbB4 is highly expressed in the cystic kidneys with polycystic kidney diseases.
      To investigate its potential role in cystogenesis, cpk mice carrying a heart
      rescued ErbB4 deletion were generated. Accelerated cyst progression and renal
      function deterioration were noted as early as 10 days postnatally in cpk mice
      with ErbB4 deletion compared to cpk mice, as indicated by increased cystic index,
      higher kidney weight to body weight ratios, and elevated BUN levels. No apparent
      defects in renal development were noted with ErbB4 deletion itself. Increased
      cell proliferation was predominately seen in the cortex of cystic kidneys with or
      without ErbB4 deletion. However, there was significantly more cell proliferation
      in the cyst-lining epithelial cells in cpk mice with ErbB4 deletion. TUNEL
      staining localized apoptotic cells mainly to the renal medulla. There were
      significantly more apoptotic cells in the cyst-lining epithelial cells in ErbB4
      deleted cpk kidneys, with decreased levels of cyclin D1, increased levels of p21,
      p27, and cleaved caspase 3. Thus, lack of ErbB4 may contribute to elevated cell
      proliferation and unbalanced cell apoptosis, resulting in accelerated cyst
      formation and early renal function deterioration. These studies suggest that the
      high level of ErbB4 expression seen in cpk mice may exert relative cytoprotective
      effects in renal epithelia. 

PMID- 24670413
TI  - No significant effect of angiotensin II receptor blockade on intermediate
      cardiovascular end points in hemodialysis patients.
AB  - Agents blocking the renin-angiotensin-aldosterone system are frequently used in
      patients with end-stage renal disease, but whether they exert beneficial
      cardiovascular effects is unclear. Here the long-term effects of the angiotensin
      II receptor blocker, irbesartan, were studied in hemodialysis patients in a
      double-blind randomized placebo-controlled 1-year intervention trial using a
      predefined systolic blood pressure target of 140 mm Hg (SAFIR study). Each group
      of 41 patients did not differ in terms of age, blood pressure, comorbidity,
      antihypertensive treatment, dialysis parameters, and residual renal function.
      Brachial blood pressure decreased significantly in both groups, but there was no
      significant difference between placebo and irbesartan. Use of additional
      antihypertensive medication, ultrafiltration volume, and dialysis dosage were not
      different. Intermediate cardiovascular end points such as central aortic blood
      pressure, carotid-femoral pulse wave velocity, left ventricular mass index, N
      terminal brain natriuretic prohormone, heart rate variability, and plasma
      catecholamines were not significantly affected by irbesartan treatment. Changes
      in systolic blood pressure during the study period significantly correlated with
      changes in both left ventricular mass and arterial stiffness. Thus, significant
      effects of irbesartan on intermediate cardiovascular end points beyond blood
      pressure reduction were absent in hemodialysis patients.

PMID- 24670414
TI  - The self-prescribed use of aromatherapy oils by pregnant women.
AB  - BACKGROUND: While some studies have reported effectiveness of aromatherapy oils
      use during labour there is no reported evidence of efficacy or risks of
      aromatherapy oils use for pregnancy-related symptoms or conditions. A number of
      aromatherapy oils are unsafe for use by pregnant women yet there is currently no
      research examining the prevalence and characteristics of women who use
      aromatherapy oils during pregnancy. AIM: To conduct an empirical study of the
      prevalence and characteristics of women who use aromatherapy oils during
      pregnancy. METHODS: The research was conducted as part of the Australian
      Longitudinal Study on Women's Health (ALSWH), focusing on the nationally
      representative sample of Australian women aged 31-36 years. Data were collected
      via a cross-sectional questionnaire (n=8200) conducted in 2009. RESULTS: Self
      prescribed aromatherapy oils were used by 15.2% of pregnant women. Pregnant women
      were 1.57 (95% CI: 1.01, 2.43) times more likely to self-prescribe use of
      aromatherapy oils if they have allergies or hayfever, and 2.26 (95% CI: 1.34,
      3.79) times more likely to self-prescribe use of aromatherapy oils if they have a
      urinary tract infection (UTI). CONCLUSION: Our study highlights a considerable
      use of aromatherapy oils by pregnant women. There is a clear need for greater
      communication between practitioners and patients regarding the use of
      aromatherapy oils during pregnancy, as well a need for health care practitioners
      to be mindful that pregnant women in their care may be using aromatherapy oils,
      some of which may be unsafe.

PMID- 24670415
TI  - Inhibition of NAD+-dependent histone deacetylases (sirtuins) causes growth arrest
      and activates both apoptosis and autophagy in the pathogenic protozoan
      Trypanosoma cruzi.
AB  - Chagas disease, which is caused by the parasite Trypanosoma cruzi, affects
      approximately 7-8 million people in Latin America. The drugs available to treat
      this disease are ineffective against chronic phase disease and are associated
      with toxic side effects. Therefore, the development of new compounds that can
      kill T. cruzi at low concentrations is critically important. Herein, we report
      the effects of a novel 3-arylideneindolin-2-one that inhibits sirtuins, which are
      highly conserved proteins that are involved in a variety of physiological
      processes. The compound KH-TFMDI was tested against the epimastigote,
      trypomastigote and amastigote forms of T. cruzi, and its effects were evaluated
      using flow cytometry, light and electron microscopy. KH-TFMDI inhibited the
      replication of T. cruzi intracellular amastigotes with an IC50 of 0.5 +/- 0.2
      MUM, which is significantly lower than the IC50 of benznidazole. The compound
      also lysed the highly infectious bloodstream trypomastigotes (BST) with LC50
      values of 0.8 +/- 0.3 MUM at 4  degrees C and 2.5 +/- 1.1 MUM at 37  degrees C.
      KH-TFMDI inhibited cytokinesis and induced several morphological changes in the
      parasite, leading to its death by apoptosis and autophagy. This study highlights
      sirtuins as a potential new target for Chagas disease therapy.

PMID- 24670417
TI  - Device lead-induced tricuspid regurgitation: does it matter?

PMID- 24670416
TI  - Quantification of pancreatic cancer proteome and phosphorylome: indicates
      molecular events likely contributing to cancer and activity of drug targets.
AB  - OBJECTIVE: LC-MS/MS phospho-proteomics is an essential technology to help unravel
      the complex molecular events that lead to and propagate cancer. We have developed
      a global phospho-proteomic workflow to determine activity of signaling pathways
      and drug targets in pancreatic cancer tissue for clinical application. METHODS:
      Peptides resulting from tryptic digestion of proteins extracted from frozen
      tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were
      labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange
      chromatography, then were analysed by LC-MS/MS directly or first enriched for
      phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and
      freeware bioinformatic platforms were used to identify relevant biological events
      from the complex dataset. RESULTS: Of 2,101 proteins identified, 152 demonstrated
      significant difference in abundance between tumor and non-tumor tissue. They
      included proteins that are known to be up-regulated in pancreatic cancer (e.g.
      Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of
      the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites),
      635 showed significant regulation, particularly those from proteins involved in
      cell migration (Rho guanine nucleotide exchange factors & MRCKalpha) and
      formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2,
      HDAC1 and other drug targets were found to be highly modulated (>=2 fold) in
      different cases highlighting their predictive power. CONCLUSION: Here we provided
      critical information enabling us to identify the common and unique molecular
      events likely contributing to cancer in each case. Such information may be used
      to help predict more bespoke therapy suitable for an individual case.

PMID- 24670418
TI  - The dialysis procedure as a trigger for atrial fibrillation: new insights in the
      development of atrial fibrillation in dialysis patients.
AB  - AIMS: Atrial fibrillation (AF) is common in dialysis patients and is associated
      with increased morbidity and mortality. The pathophysiology may be related to
      common risk factors for both AF and renal disease or to dialysis-specific
      factors. The purpose of this study was to determine whether and how AF onset
      relates to the dialysis procedure itself. METHODS: All dialysis patients enrolled
      in the implantable cardioverter defibrillator-2 (ICD-2) trial until January 2012,
      who were implanted with an ICD, were included in this study. Using the ICD remote
      monitoring function, the exact time of onset of all AF episodes was registered.
      Subsequently, this was linked to the timing of dialysis procedures. RESULTS: For
      the current study, a total of 40 patients were included, follow-up was 28 +/- 16
      months, 80% male, 70 +/- 8 years old. A total of 428 episodes of AF were
      monitored in 14 patients. AF onset was more frequent on the days of haemodialysis
      (HD) (p<0.001) and specifically increased during the dialysis procedure itself
      (p=0.04). Patients with AF had a larger left atrium (p<0.001) and a higher
      systolic blood pressure before and after HD (p<0.001). CONCLUSION: This study
      provides insight in the exact timing of AF onset in relation to the dialysis
      procedure itself. In HD patients, AF occurred significantly more often on a
      dialysis day and especially during HD. These findings might help to elucidate
      some aspects of the pathophysiology of AF in dialysis patients and could
      facilitate early detection of AF in these high-risk patients.

PMID- 24670419
TI  - External support of the dilated aorta: back to the future?

PMID- 24670420
TI  - Beneficial effects of catheter ablation of frequent premature ventricular
      complexes on left ventricular function.
AB  - BACKGROUND: Frequent premature ventricular complexes (PVCs) are associated with a
      reversible form of LV dysfunction. OBJECTIVE: We performed a meta-analysis to
      evaluate the effects of catheter ablation on improvement of LV function in
      patients with frequent PVCs. METHODS: We searched MEDLINE for cohort studies of
      patients who underwent catheter ablation of frequent PVCs. LVEF both before and
      postablation was reported. The endpoints were changes from baseline in both LVEF
      and LV end-diastolic diameter (LVEDd) postablation. Quantitative analysis of
      continuous variables was performed according to random effect methods by
      MetaAnalyst Beta 3.13 software. Association between site of origin (SOO) of PVCs
      and degree of LVEF improvement was evaluated by meta-regression using STATA
      V.12.0 software. Subgroup analysis of patients with LV dysfunction at baseline
      was performed. RESULTS: Fifteen studies with a total of 712 patients were
      included. The mean PVC burden before catheter ablation was 24% (95% CI 19% to
      29%). The long-term success rate of PVC ablation ranged from 66% to 90%. The
      overall mean increase from baseline in LVEF postablation was 7.7% (95% CI 6.1% to
      9.4%) and the overall mean decrease in LVEDd was -4.6 mm (95% CI -6.0 to -3.1
      mm). Meta-regression showed no significant association of SOO of PVCs with the
      degree of postablation LVEF improvement. Subgroup analysis showed that the
      overall mean increase from baseline in LVEF postablation was 12.4% (95% CI 8.1%
      to 16.6%) and the overall mean decrease in LVEDd was -4.8 mm (95% CI -6.2 to -3.4
      mm) in patients with LV dysfunction at baseline. CONCLUSIONS: Ablation of
      frequent PVCs improves cardiac function, especially for patients with LV
      dysfunction.

PMID- 24670421
TI  - Evidence of a putative deep sea specific microbiome in marine sponges.
AB  - The microbiota of four individual deep water sponges, Lissodendoryx diversichela,
      Poecillastra compressa, Inflatella pellicula, and Stelletta normani, together
      with surrounding seawater were analysed by pyrosequencing of a region of the 16S
      rRNA gene common to Bacteria and Archaea. Due to sampling constraints at depths
      below 700 m duplicate samples were not collected. The microbial communities of L.
      diversichela, P. compressa and I. pellicula were typical of low microbial
      abundance (LMA) sponges while S. normani had a community more typical of high
      microbial abundance (HMA) sponges. Analysis of the deep sea sponge microbiota
      revealed that the three LMA-like sponges shared a set of abundant OTUs that were
      distinct from those associated with sponges from shallow waters. Comparison of
      the pyrosequencing data with that from shallow water sponges revealed that the
      microbial communities of all sponges analysed have similar archaeal populations
      but that the bacterial populations of the deep sea sponges were distinct. Further
      analysis of the common and abundant OTUs from the three LMA-like sponges placed
      them within the groups of ammonia oxidising Archaea (Thaumarchaeota) and sulphur
      oxidising gamma-Proteobacteria (Chromatiales). Reads from these two groups made
      up over 70% of all 16S rRNA genes detected from the three LMA-like sponge
      samples, providing evidence of a putative common microbial assemblage associated
      with deep sea LMA sponges. 

PMID- 24670422
TI  - Refining climate change projections for organisms with low dispersal abilities: a
      case study of the Caspian whip snake.
AB  - Climate warming is one of the most important threats to biodiversity. Ectothermic
      organisms such as amphibians and reptiles are especially vulnerable as climatic
      conditions affect them directly. Ecological niche models (ENMs) are increasingly
      popular in ecological studies, but several drawbacks exist, including the limited
      ability to account for the dispersal potential of the species. In this study, we
      use ENMs to explore the impact of global climate change on the Caspian whip snake
      (Dolichophis caspius) as model for organisms with low dispersal abilities and to
      quantify dispersal to novel areas using GIS techniques. Models generated using
      Maxent 3.3.3 k and GARP for current distribution were projected on future
      climatic scenarios. A cost-distance analysis was run in ArcGIS 10 using
      geomorphological features, ecological conditions, and human footprint as "costs"
      to dispersal of the species to obtain a Maximum Dispersal Range (MDR) estimate.
      All models developed were statistically significant (P<0.05) and recovered the
      currently known distribution of D. caspius. Models projected on future climatic
      conditions using Maxent predicted a doubling of suitable climatic area, while
      GARP predicted a more conservative expansion. Both models agreed on an expansion
      of suitable area northwards, with minor decreases at the southern distribution
      limit. The MDR area calculated using the Maxent model represented a third of the
      total area of the projected model. The MDR based on GARP models recovered only
      about 20% of the total area of the projected model. Thus, incorporating measures
      of species' dispersal abilities greatly reduced estimated area of potential
      future distributions. 

PMID- 24670423
TI  - Echinocandins in the treatment of candidaemia and invasive candidiasis: clinical
      and economic perspectives.
AB  - Candidaemia and invasive candidiasis (IC) complicate modern medical therapy,
      contributing to high morbidity and mortality. Managing candidiasis is costly,
      with an additional healthcare expenditure of nearly US$300 million annually.
      Recent consensus guidelines have suggested the use of newer antifungal agents,
      such as echinocandins, for the treatment of candidaemia and IC owing to promising
      clinical outcomes compared with older-generation antifungal agents, but at higher
      drug acquisition and administration costs. Comprehensive cost-effectiveness data
      for echinocandins in treating candidaemia and IC remain relatively scant,
      underlining the need for more studies to incorporate robust economic analyses
      into clinical decisions. Assessment of the cost efficiencies of these expensive
      antifungal agents is essential for maximising health outcomes within the
      constraints of healthcare resources. This review will explore the epidemiology of
      candidaemia and IC in the context of clinical and economic aspects of the
      antifungal agents used to treat IC, especially the echinocandins. Standardising
      the outcome measure, methodology and reporting of results used in economic
      studies is central to ensure validity and comparability of the findings. Future
      studies comparing the economic advantages of all available antifungal treatment
      options and in the context of new diagnostic tools for fungal infections are
      anticipated. 

PMID- 24670424
TI  - NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked
      polyubiquitination of RICK and TRAF6.
AB  - It is well established that polymorphisms of the caspase activation and
      recruitment domain 15 (CARD15) gene, a major risk factor in Crohn's disease (CD),
      lead to loss of nucleotide-binding oligomerization domain 2 (NOD2) function.
      However, a molecular explanation of how such loss of function leads to increased
      susceptibility to CD has remained unclear. In a previous study exploring this
      question, we reported that activation of NOD2 in human dendritic cells by its
      ligand, muramyl dipeptide (MDP), negatively regulates Toll-like receptor (TLR)
      mediated inflammatory responses. Here we show that NOD2 activation results in
      increased interferon regulatory factor 4 (IRF4) expression and binding to tumor
      necrosis factor receptor associated factor 6 (TRAF6) and RICK (receptor
      interacting serine-threonine kinase). We then show that such binding leads to
      IRF4-mediated inhibition of Lys63-linked polyubiquitination of TRAF6 and RICK and
      thus to downregulation of nuclear factor (NF)-kappaB activation. Finally, we
      demonstrate that protection of mice from the development of experimental colitis
      by MDP or IRF4 administration is accompanied by similar IRF4-mediated effects on
      polyubiquitination of TRAF6 and RICK in colonic lamina propria mononuclear cells.
      These findings thus define a mechanism of NOD2-mediated regulation of innate
      immune responses to intestinal microflora that could explain the relation of
      CARD15 polymorphisms and resultant NOD2 dysfunction to CD. 

PMID- 24670425
TI  - The mucosal inflammatory response to non-typhoidal Salmonella in the intestine is
      blunted by IL-10 during concurrent malaria parasite infection.
AB  - Coinfection can markedly alter the response to a pathogen, thereby changing its
      clinical presentation. For example, non-typhoidal Salmonella (NTS) serotypes are
      associated with gastroenteritis in immunocompetent individuals. In contrast,
      individuals with severe pediatric malaria can develop bacteremic infections with
      NTS, during which symptoms of gastroenteritis are commonly absent. Here we report
      that, in both a ligated ileal loop model and a mouse colitis model, malaria
      parasites caused a global suppression of gut inflammatory responses and blunted
      the neutrophil influx that is characteristic of NTS infection. Further, malaria
      parasite infection led to increased recovery of Salmonella enterica serotype
      Typhimurium from the draining mesenteric lymph node (MLN) of mice. In the mouse
      colitis model, blunted intestinal inflammation during NTS infection was
      independent of anemia but instead required parasite-induced synthesis of
      interleukin (IL)-10. Blocking of IL-10 in coinfected mice reduced dissemination
      of S. Typhimurium to the MLN, suggesting that induction of IL-10 contributes to
      development of disseminated infection. Thus IL-10 produced during the immune
      response to malaria in this model contributes to suppression of mucosal
      inflammatory responses to invasive NTS, which may contribute to differences in
      the clinical presentation of NTS infection in the setting of malaria. 

PMID- 24670426
TI  - Toll-like receptor 6 stimulation promotes T-helper 1 and 17 responses in
      gastrointestinal-associated lymphoid tissue and modulates murine experimental
      colitis.
AB  - T-helper 1 and 17 (Th1/Th17) responses are important in inflammatory bowel
      disease (IBD), and research indicates that Toll-like receptor 6 (TLR6)
      stimulation leads to Th17 cell development within the lung. The gastrointestinal
      tract, like the lung, is a mucosal surface that is exposed to bacterially derived
      TLR6 ligands. Thus, we looked at the effects of TLR6 stimulation on the
      expression of Th17-, Th1-, and regulatory T-cell-associated transcription
      factors; RORgammat, T-bet, and Foxp3, respectively; in CD4+ T cells within gut
      associated lymphoid tissue (GALT) in vitro and in vivo. Cells from GALT and
      spleen were stimulated with anti-CD3 and TLR ligands for TLR1/2 and TLR2/6
      (Pam3CSK4 and FSL-1, respectively). FSL-1 was more effective than Pam3CSK4 at
      inducing Th1 and Th17 responses in the GALT while Pam3CSK4 rivaled FSL-1 in the
      spleen. TLR6 was further explored in vivo using experimental colitis. Tlr6-/-
      mice were resistant to colitis, and oral FSL-1 led to more severe colitis in wild
      type mice. Similar pro-inflammatory reactions were seen in human peripheral blood
      mononuclear cells, and TLR6 expression was directly correlated with RORC mRNA
      levels in inflamed intestines of IBD patients. These results demonstrate that
      TLR6 supports Th1- and Th17-skewed responses in the GALT and might be an
      important target for the development of new medical interventions in IBD. 

PMID- 24670428
TI  - Feasibility of aerosol drug delivery to sleeping infants: a prospective
      observational study.
AB  - OBJECTIVES: Delivery of inhaled medications to infants is usually very demanding
      and is often associated with crying and mask rejection. It has been suggested
      that aerosol administration during sleep may be an attractive alternative.
      Previous studies in sleeping children were disappointing as most of the children
      awoke and rejected the treatment. The SootherMask (SM) is a new, gentle and
      innovative approach for delivering inhaled medication to infants and toddlers.
      The present pilot study describes the feasibility of administering inhaled
      medications during sleep using the SM. DESIGN: Prospective observational study.
      SETTING: Out patients. PARTICIPANTS: 13 sleeping infants with recurrent wheezing
      who regularly used pacifiers and were <12 months old. INTERVENTION: Participants
      inhaled technetium99mDTPA-labelled normal saline aerosol delivered via a Respimat
      Soft Mist Inhaler (SMI) (Boehringer-Ingelheim, Germany) and SM + InspiraChamber
      (IC; InspiRx Inc, New Jersey, USA). OUTCOMES: The two major outcomes were the
      acceptability of the treatment and the lung deposition (per cent of emitted
      dose). RESULTS: All infants who fulfilled the inclusion criteria successfully
      received the SM treatment during sleep without difficulty. Mean lung deposition
      (+/-SD) averaged 1.6+/-0.5% in the right lung. CONCLUSIONS: This study
      demonstrated that the combination of Respimat, IC and SM was able to administer
      aerosol therapy to all the sleeping infants who were regular pacifier users with
      good lung deposition. Administration of aerosols during sleep is advantageous
      since all the sleeping children accepted the mask and ensuing aerosol therapy
      under these conditions, in contrast to previous studies in which there was
      frequent mask rejection using currently available devices. CLINICAL TRIAL
      REGISTRY: NCT01120938.

PMID- 24670427
TI  - Targeted colonic claudin-2 expression renders resistance to epithelial injury,
      induces immune suppression, and protects from colitis.
AB  - Expression of claudin-2, a tight junction protein, is highly upregulated during
      inflammatory bowel disease (IBD) and, due to its association with epithelial
      permeability, has been postulated to promote inflammation. Notably, claudin-2 has
      also been implicated in the regulation of intestinal epithelial proliferation.
      However, precise role of claudin-2 in regulating colonic homeostasis remains
      unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic mice, that
      increased colonic claudin-2 expression augments mucosal permeability as well as
      colon and crypt length. Most notably, despite leaky colon, Cl-2TG mice were
      significantly protected against experimental colitis. Importantly, claudin-2
      expression increased colonocyte proliferation and provided protection against
      colitis-induced colonocyte death in a PI-3Kinase/Bcl-2-dependent manner. However,
      Cl-2TG mice also demonstrated marked suppression of colitis-induced increases in
      immune activation and associated signaling, suggesting immune tolerance.
      Accordingly, colons from naive Cl-2TG mice harbored significantly increased
      numbers of regulatory (CD4(+)Foxp3(+)) T cells than WT littermates. Furthermore,
      macrophages isolated from Cl-2TG mouse colon exhibited immune anergy.
      Importantly, these immunosuppressive changes were associated with increased
      synthesis of the immunoregulatory cytokine TGF-beta by colonic epithelial cells
      in Cl-2TG mice compared with WT littermates. Taken together, our findings reveal
      a critical albeit complex role of claudin-2 in intestinal homeostasis by
      regulating epithelial permeability, inflammation and proliferation and suggest
      novel therapeutic opportunities. 

PMID- 24670429
TI  - Individualisation of drug treatments for patients with long-term conditions: a
      review of concepts.
AB  - OBJECTIVES: Patients and policy makers advocate that drug treatments should be
      individualised. However, the term is used in a variety of ways. We set out to
      identify the range of related terminology and concepts in the general field of
      individualisation, map out the relationships between these concepts and explore
      how patients' perspectives are considered. DESIGN: We consulted members of an
      established patient and public involvement group about their experience of
      medicine taking for long-term conditions and their ideas about individualisation.
      We then conducted a scoping review of the literature to explore how terms
      surrounding individualisation of drug treatment are used and defined in the
      literature, and to explore the extent to which patients' perspectives are
      represented, with a view to informing future recommendations as to how
      individualisation can be operationalised. METHODS: We identified relevant
      literature using a range of search strategies. Two researchers independently
      extracted definitions of terms using a template. Inductive and deductive methods
      were used to explore the data. RESULTS: Definitions were categorised according to
      the following themes: medical management; pharmacogenetics, the patient's
      perspective; interactions between the healthcare provider and patient and
      management of long-term conditions. CONCLUSIONS: Within the literature reviewed,
      the involvement of patients in the ongoing management of drug treatment was
      largely absent. We propose the use of a new term 'mutually agreed tailoring'
      (MAT). This describes the ongoing pharmacological management of conditions that
      incorporates patients' specific needs, experiences and existing strategies for
      using their medications, and the professionals' clinical judgement. This usually
      includes patients monitoring their symptoms and, with the support of the
      professional, making appropriate product, dose or timing adjustments as
      necessary. Our previous work suggests that many patients and doctors are
      successfully practising MAT, so we suggest that a formal description may
      facilitate wider utilisation of strategies that will improve patient outcomes.

PMID- 24670430
TI  - Sexual minority population density and incidence of lung, colorectal and female
      breast cancer in California.
AB  - OBJECTIVE: Risk factors for breast, colorectal, and lung cancer are known to be
      more common among lesbian, gay, and bisexual (LGB) individuals, suggesting they
      may be more likely to develop these cancers. Our objective was to determine
      differences in cancer incidence by sexual orientation, using sexual orientation
      data aggregated at the county level. METHODS: Data on cancer incidence were
      obtained from the California Cancer Registry and data on sexual orientation were
      obtained from the California Health Interview Survey, from which a measure of age
      specific LGB population density by county was calculated. Using multivariable
      Poisson regression models, the association between the age-race-stratified
      incident rate of breast, lung and colorectal cancer in each county and LGB
      population density was examined, with race, age group and poverty as covariates.
      RESULTS: Among men, bisexual population density was associated with lower
      incidence of lung cancer and with higher incidence of colorectal cancer. Among
      women, lesbian population density was associated with lower incidence of lung and
      colorectal cancer and with higher incidence of breast cancer; bisexual population
      density was associated with higher incidence of lung and colorectal cancer and
      with lower incidence of breast cancer. CONCLUSIONS: These study findings clearly
      document links between county-level LGB population density and cancer incidence,
      illuminating an important public health disparity.

PMID- 24670431
TI  - Investments in respiratory infectious disease research 1997-2010: a systematic
      analysis of UK funding.
AB  - OBJECTIVES: Respiratory infections are responsible for a large global burden of
      disease. We assessed the public and philanthropic investments awarded to UK
      institutions for respiratory infectious disease research to identify areas of
      underinvestment. We aimed to identify projects and categorise them by pathogen,
      disease and position along the research and development value chain. SETTING: The
      UK. PARTICIPANTS: Institutions that host and carry out infectious disease
      research. PRIMARY AND SECONDARY OUTCOME MEASURES: The total amount spent and
      number of studies with a focus on several different respiratory pathogens or
      diseases, and to correlate these against the global burden of disease; also the
      total amount spent and number of studies relating to the type of science, the
      predominant funder in each category and the mean and median award size. RESULTS:
      We identified 6165 infectious disease studies with a total investment of L2.6
      billion. Respiratory research received L419 million (16.1%) across 1192 (19.3%)
      studies. The Wellcome Trust provided greatest investment (L135.2 million; 32.3%).
      Tuberculosis received L155 million (37.1%), influenza L80 million (19.1%) and
      pneumonia L27.8 million (6.6%). Despite high burden, there was relatively little
      investment in vaccine-preventable diseases including diphtheria (L0.1 million,
      0.03%), measles (L5.0 million, 1.2%) and drug-resistant tuberculosis. There were
      802 preclinical studies (67.3%) receiving L273 million (65.2%), while
      implementation research received L81 million (19.3%) across 274 studies (23%).
      There were comparatively few phase I-IV trials or product development studies.
      Global health research received L68.3 million (16.3%). Relative investment was
      strongly correlated with 2010 disease burden. CONCLUSIONS: The UK predominantly
      funds preclinical science. Tuberculosis is the most studied respiratory disease.
      The high global burden of pneumonia-related disease warrants greater investment
      than it has historically received. Other priority areas include antimicrobial
      resistance (particularly within tuberculosis), economics and proactive
      investments for emerging infectious threats.

PMID- 24670432
TI  - Outcome expectations and physical activity in persons with longstanding multiple
      sclerosis.
AB  - Research suggests that persons with multiple sclerosis (MS) are much less
      physically active than the general population and that increased physical
      activity in persons with MS is associated with numerous benefits such as
      improvements in fatigue, mobility, and quality of life (). Potentially modifiable
      theory-based determinants of physical activity behavior need to be identified so
      that researchers may study their effectiveness in randomized clinical trials and
      clinicians may integrate them into practice to promote physical activity in this
      population. The purpose of this study was to explore the multidimensional
      (physical, social, and self-evaluative) outcome expectations for physical
      activity among persons with longstanding MS. A sample of 369 participants
      diagnosed with MS for more than 15 years completed surveys to measure
      multidimensional outcome expectations for exercise, MS functional limitations,
      and physical activity using two different instruments: one measuring physical
      activity engagement and the other measuring physical activity capability. Results
      indicated that MS functional limitation was the strongest predictor of both
      physical activity engagement and physical activity capability. Physical and
      social outcome expectations contributed to the model explaining 12% of the
      variation in physical activity engagement, whereas none of the outcome expectancy
      dimensions (physical, social, or self-evaluative) contributed to the model
      explaining variation in physical activity capability. Although analyses of cross
      sectional data do not infer causation, these findings suggest that positive
      physical and social outcome expectations for physical activity are associated
      with engagement in physical activity as well as being potential sources of
      motivation for increasing physical activity behavior in individuals living with
      longstanding MS. 

PMID- 24670433
TI  - Screening, diagnosis, and treatment of post-stroke depression.
AB  - Depression is a common finding after an acute stroke and often interferes with
      the ability of the patient to participate in the rehabilitation process. A
      literature review was conducted to investigate the potential benefit of the early
      administration of antidepressant medication on the rate of depression after acute
      stroke. Current practices for screening and diagnosing post-stroke depression
      (PSD) were also reviewed. MEDLINE, CINAHL, Cochrane Library databases, and
      PsychInfo were searched for relevant articles published in English up to August
      2012. One of the challenges identified was that although several studies suggest
      benefit to the addition of antidepressant medication, little consistency exists
      in the timing of the intervention, particularly in regards to rehabilitation.
      Although patients reporting fewer depressive symptoms have been shown to have
      higher levels of participation in post-stroke therapy, conclusions regarding the
      benefit of early intervention cannot be made at this time. However, several
      studies do suggest that, in addition to the benefit of treating PSD, different
      classes of antidepressant medication may actually facilitate the neural
      mechanisms of recovery in patients with stroke. Overall, although the current
      available research cannot recommend the routine administration of antidepressant
      medication for PSD, the current research can support the administration of this
      pharmaceutical intervention on an individual basis. Future research needs
      surrounding PSD are vast, and several questions need to be addressed before
      focusing on the timing and benefit of early intervention including developing a
      universally validated screening tool, developing a definitive definition, and
      establishing acceptable treatment recommendations. Once these topics are further
      explored, the potential for antidepressants to improve neural mechanisms of
      recovery can also be further investigated. 

PMID- 24670434
TI  - Chronic morbidities after traumatic brain injury: an update for the advanced
      practice nurse.
AB  - Emerging data suggest that traumatic brain injury (TBI) is a disease process with
      considerable long-range morbidities requiring lifelong monitoring and treatment.
      Multiple chronic morbidities develop across the life span after TBI, including
      mental health disorders, headaches, seizures, and neuroendocrine imbalances as
      well as chronic diseases. Still, there has been limited focus on effective guides
      and strategies for helping persons with TBI meet their chronic health needs as
      they live with the consequences of TBI. The advanced practice nurse is well
      positioned to participate collaboratively in practices that promote health
      screening and chronic disease management after TBI to ameliorate distress and
      enhance quality of life as persons with TBI live with lifelong consequences. 

PMID- 24670436
TI  - Changes of response patterns to excitatory stimuli of different intensities: a
      model-based study of cochlear nucleus neurons.
AB  - OBJECTIVE: The cochlear nucleus (CN) neurons show 3 principal response patterns
      to short tone bursts, namely the primary-like, chopper and onset response
      patterns. We previously established an excitatory model to simulate the response
      patterns of CN neurons to stimuli. In this study, we aimed to investigate the
      effects of excitatory intensity on the CN neuron response patterns and explore
      the role of inhibitory inputs under normal physiological conditions. METHODS:
      Based on the platform of Matlab and the excitatory model derived from the
      integrate-and-fire model, we altered the intensity of excitatory inputs in dB
      range and obtained the histograms to analyze the changes in the response patterns
      of the neurons using OriginPro 7.5 data analysis software. RESULTS: The original
      primary-like response pattern of the neurons did not vary significantly while the
      chopper and onset response patterns changed into primary-like responses with the
      increase of the excitatory input intensity. But this response pattern alteration
      as a result of excitatory input intensity changes was rarely observed under
      normal physiological conditions. CONCLUSIONS: The CN neurons receive balanced
      excitatory and inhibitory inputs, which stabilize the neuronal membrane potential
      within a limited range. The balanced inhibitory inputs decide the response
      pattern of a given neuron.

PMID- 24670435
TI  - Climate extreme effects on the chemical composition of temperate grassland
      species under ambient and elevated CO2: a comparison of fructan and non-fructan
      accumulators.
AB  - Elevated CO2 concentrations and extreme climate events, are two increasing
      components of the ongoing global climatic change factors, may alter plant
      chemical composition and thereby their economic and ecological characteristics,
      e.g. nutritional quality and decomposition rates. To investigate the impact of
      climate extremes on tissue quality, four temperate grassland species: the fructan
      accumulating grasses Lolium perenne, Poa pratensis, and the nitrogen (N) fixing
      legumes Medicago lupulina and Lotus corniculatus were subjected to water deficit
      at elevated temperature (+3 degrees C), under ambient CO2 (392 ppm) and elevated
      CO2 (620 ppm). As a general observation, the effects of the climate extreme were
      larger and more ubiquitous in combination with elevated CO2. The imposed climate
      extreme increased non-structural carbohydrate and phenolics in all species,
      whereas it increased lignin in legumes and decreased tannins in grasses. However,
      there was no significant effect of climate extreme on structural carbohydrates,
      proteins, lipids and mineral contents and stoichiometric ratios. In combination
      with elevated CO2, climate extreme elicited larger increases in fructan and
      sucrose content in the grasses without affecting the total carbohydrate content,
      while it significantly increased total carbohydrates in legumes. The accumulation
      of carbohydrates in legumes was accompanied by higher activity of sucrose
      phosphate synthase, sucrose synthase and ADP-Glc pyrophosphorylase. In the
      legumes, elevated CO2 in combination with climate extreme reduced protein,
      phosphorus (P) and magnesium (Mg) contents and the total element:N ratio and it
      increased phenol, lignin, tannin, carbon (C), nitrogen (N) contents and C:N, C:P
      and N:P ratios. On the other hand, the tissue composition of the fructan
      accumulating grasses was not affected at this level, in line with recent views
      that fructans contribute to cellular homeostasis under stress. It is speculated
      that quality losses will be less prominent in grasses (fructan accumulators) than
      legumes under climate extreme and its combination with elevated CO2 conditions. 

PMID- 24670437
TI  - [Analysis of clinical and imaging features of cardiac amyloidosis: a multicenter
      study].
AB  - OBJECTIVE: To summarize the features of clinical manifestations, laboratory tests
      and imaging findings of patients with cardiac amyloidosis (CA). METHODS: A total
      of 60 CA patients (including 41 male and 19 female patients) from 4 centers
      admitted between May, 2012 and November, 2013 were included in the study. The
      demographic data, medical history, clinical manifestations, laboratory test data,
      ECG, cardiac ultrasound, and cardiac magnetic resonance (CMR) imaging of the
      patients were analyzed. RESULTS: Two-thirds of the 60 CA patients, were middle
      aged or elderly men, and 47% of the patients had AL-CA. The clinical
      manifestations included exertional dyspnea (73%), pedal edema (47%), hypotension
      (47%), and hypertrophy of the tongue (22%); abnormal laboratory test results
      included albuminuria (53%) and liver (15%) and kidney (28%) dysfunction; blood
      routine, urine and serum immunoglobulin quantification and immunofixation
      electrophoresis could help the screening of AL-CA. Kidney (53%) and liver (15%)
      involvement was common, and 86% of AL-CA patients had kidney involvement. Typical
      ECG characteristics included poor R wave progression (35%), low voltage in limb
      leads (33%), and a pseudo infarct Q wave (30%); the latter two were more frequent
      in AL-CA. The characteristics of ultrasound findings included left ventricle
      thickening (100%), left atrial enlargement (87%) and enhanced echo of the
      myocardial granules(92%), and diastolic dysfunction was obvious in all the CA
      patients regardless of the systolic function. The DT and E/e' of the mitral
      annulus could be used as an index to evaluate diastolic dysfunction in early
      stage of the disease. Left ventricular (LV) global subendocardial late gadolinium
      enhancement (LGE, 81%) accompanied by right ventricular (RV) and atrial LGE was
      the typical characteristic of CMR, and the range of LGE in the RV and the two
      atria was wider in AL-CA than in non-AL-CA. NT-proBNP (97%) and cardiac troponin
      (53%) in CA patients were both elevated, which helped in diagnosing and assessing
      the severity of cardiac involvement, according to which 50% of the patients were
      found to be at a high risk, 43% at an intermediate risk, and 7% at a low risk.
      CONCLUSION: The combination of the features of clinical, laboratory tests and
      imaging findings of CA have important diagnostic and prognostic value for CA.

PMID- 24670438
TI  - [Dexmedetomidine inhibits 5-HT-induced intrapulmonary artery vasoconstriction].
AB  - OBJECTIVE: To investigate the effect of dexmedetomidine on 5-HT-induced
      constrictions of isolated human intrapulmonary arteries and explore the
      mechanisms. METHODS: Lung tissue was obtained from patients undergoing surgery
      for lung carcinoma. Intrapulmonary arteries were dissected and cut into rings,
      which were mounted in a Multi Myograph system to determine the effect of
      dexmedetomidine (0.3-3 nmol/L) on 5-HT-induced vasoconstrictions. The influences
      of the endothelium removal and various drugs including L-NAME, yohimbine and
      indomethacin were tested on the effects of dexmedetomidine. RESULTS:
      Dexmedetomidine (0.1-100 nmol/L) did not obviously affect the resting tension of
      endothelium-intact human intrapulmonary arteries. 5-HT induced concentration
      dependent contraction in endothelium-intact intrapulmonary arteries [pD2:
      6.11?0.05, Emax: (102.10?1.96)%]. In the rings with intact endothelium,
      dexmedetomidine (0.3-3 nmol/L) significantly attenuated the Emax and pD2 of 5-HT
      induced vasoconstriction [pD2: 5.94?0.03, Emax: (79.96?1.31)%]. 5-HT also induced
      concentration-dependent contraction in endothelium-denuded intrapulmonary
      arteries [pD2: 6.10?0.07, Emax: (107.40?3.20)%]. Dexmedetomidine produced no
      significant effects on the rings with denuded endothelium. The effects of
      dexmedetomidine on 5-HT-induced vasoconstriction was suppressed by L-NAME and
      yohimbine, but not by indomethacin. CONCLUSION: Dexmedetomidine can inhibit 5-HT
      induced vasoconstriction of isolated human intrapulmonary arteries probably
      through alpha2-adrenergic acceptor and NO released from the endothelium.

PMID- 24670439
TI  - [Construction of pcDNA3-HERG-G572R expression vector and establishment of a cell
      line stably expressing HKE-HERG-G572R].
AB  - OBJECTIVE: To construct the pcDNA3-HERG-G572R expression vector and establish a
      cell line stably expressing HKE-HERG-G572R. METHODS: HERG-G572R mutant fragment
      was constructed by over-lap extension PCR and validated by DNA sequencing. The
      HKE-HERG-G572R expression vector was constructed and transfected into HEK293
      cells to obtain a cell line stably expressing HKE-HERG-G572R. RESULTS: The pcDNA3
      HERG-G572R expression vector was successfully constructed and the cell line
      stably expressing HKE-HERG-G572R was established. Real-time PCR and Western
      blotting revealed a 632-fold HKE-HERG-G572R overexpression in the transfected
      HEK293 cells as compared with that in control HEK293 cells transfected with
      pcDNA3 (P<0.01). CONCLUSION: The protocol can be used to construct the cell line
      stably expressing HKE-HERG-G572R to provide a cell model for studying
      individualized therapy.

PMID- 24670440
TI  - [Myocardial injury in rats following a sudden increase of altitudes].
AB  - OBJECTIVE: To investigate the influence of a sudden increase of altitudes (within
      2500 m) in winter on cardiomyocyte functions in rats. METHODS: Thirty male Wistar
      rats were randomly divided into groups A (55 m), B (1520 m), and C (2260 m) and
      subjected to simulated conditions at the indicated altitudes in winter for 3
      days. Blood gas analysis, venous blood biochemistry, and measurements of SOD
      activity and myocardial concentrations of MDA and NO were performed.
      Histopathological changes in the left ventricle were observed with HE staining
      and electron microscopy. RESULTS: Blood pH and PCO2 did not differ significantly
      between the 3 groups, but PO2 and BE in groups B and C decreased significantly
      compared with those in group A (P<0.01). Compared with group A, the rats in group
      C showed obviously increased myocardial enzymes, MYB, Tn-I, and MDA contents
      (P<0.01) with significantly decreased SOD activity (P<0.05); both groups B and C
      showed significantly decreased NO content in the myocardium (P<0.01).
      Histopathologically, the myocardial fiber in group C showed irregular alignment,
      disruption, and mitochondrial expansion. CONCLUSION: A sudden increase of
      altitude to 2260 m in winter can potentially cause hypoxic cardiomyocyte damage
      as a result of oxidative and environmental stresses.

PMID- 24670441
TI  - [Co-expression of BMP2 and Sox9 promotes chondrogenic differentiation of
      mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To investigate the effect of co-expression of bone morphogenetic
      protein 2 (BMP2) and Sox9 on chondrogenic differentiation of mesenchymal stem
      cells (MSCs) in vitro and provide experimental evidence for tissue engineering of
      cartilage. METHODS: Mouse embryonic bone marrow MSC C3H10T1/2 cells were infected
      with recombinant adenovirus expressing BMP2, Sox9 and green fluorescent protein
      (GFP) for 3-14 days, with cells infected with the adenovirus carrying GFP gene as
      the control. The mRNA expression of the markers of chondrogenic differentiation,
      including collagen type II (Col2a1), aggrecan (ACAN), and collagen type X
      (Col10a1), were determined by real-time PCR. Alcian blue staining was used for
      quantitative analysis of sulfated glycosaminoglycan in the cellular matrix. The
      expression of Col2a1 protein was assayed by immunohistochemical staining and
      Western blot analysis. RESULTS: Adenovirus-mediated BMP2 expression induced
      chondrogenic differentiation of C3H10T1/2 cells. Overexpression of Sox9
      effectively enhanced BMP2-induced expression of the chondrogenic markers Col2a1,
      aggrecan and Col10a1 mRNAs, and promoted the synthesis of sulfated
      glycosaminoglycan and Col2a1 protein in C3H10T1/2 cells. CONCLUSION: Co
      expression of BMP2 and Sox9 can promote chondrogenic differentiation of MSCs in
      vitro, which provides a new strategy for tissue engineering of cartilage.

PMID- 24670442
TI  - [beta-amyloid peptide deposition and expression of related miRNAs in the
      cerebellum of a mouse model of Alzheimer's disease].
AB  - OBJECTIVE: To investigate the presence of beta-amyloid peptide (Abeta) deposition
      in the cerebellum and the expression of related miRNAs in the cerebellum of a
      mouse model of Alzheimer disease. METHODS: Twelve 12-month-old APPswe/PSdeltaE9
      double transgenic mice and 12 wild-type C57 mice were sacrificed and the brain
      tissues were taken for examination. The right hemisphere was stained with Congo
      red to observe the deposition of amyloid substances, and from the left
      hemisphere, the hippocampus and the cerebellum were dissected for detecting the
      expression of miRNA-135a-5p, miRNA-298-5p, miRNA-466b-3p and miR-669f-3p using
      real-time PCR. RESULTS: Congo red staining revealed the presence of Abeta
      deposition in both the hippocampus and the cerebellum of the transgenic mice but
      not in the control mice. Real-time PCR showed a significantly lower expression of
      the 4 miRNAs in the hippocampus in the transgenic mice than in the control mice
      (P<0.05). The expression of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p in the
      cerebellum was significantly lower in the transgenic mice than in the control
      mice (P<0.05). The expression of miRNA-298-5p and miR-669f-3p in the hippocampus
      was significantly lower than that in the cerebellum of the transgenic mice
      (P<0.05). CONCLUSION: beta deposition also occurs in the cerebellum of
      APPswe/PSdeltaE9 double transgenic mice, and its formation might be related to
      the down-regulation of miRNA-135a-5p, miRNA-298-5p, and miR-669f-3p.

PMID- 24670443
TI  - [Peperphentonamine hydrochloride protects against gentamicin-induced cochlea
      damage by lowering cochlear caspase-3 expression in guinea pigs].
AB  - OBJECTIVE: To study the protective effect of peperphentonamine hydrochloride
      (PPTA) against gentamicin-induced cochlear damage and its mechanism to inhibit
      cell apoptosis. METHODS: Guinea pigs with normal hearing were randomized into
      control, gentamicin, and PPTA treatment groups, and the guinea pigs models of
      gentamicin-induced cochlear damage received intraperitoneal injection of PPTA.
      The changes of hearing of the guinea pigs were evaluated with auditory brainstem
      response (ABR) test, and the protein expression of caspase-3 in the cochlear
      tissue was detected using Western blotting. TUNEL staining, scanning and
      transmission electron microscopy were performed to observe the morphological
      changes of the cochlea. RESULTS: The threshold in ABR in PPTA treatment group was
      significantly higher than that in the control group (P<0.05) but significantly
      lower than that in gentamicin group. Western blotting showed a significantly
      increased caspase-3 expression in gentamicin group (P<0.001); caspase-3
      expression in PPTA group was obviously higher than that in the control group but
      much lower than that in gentamicin group (P<0.001). TUNEL assay and electron
      microscopy revealed serious damages of the hair cells in gentamicin group with
      numerous apoptotic cells in the organ of Corti, stria vascularis and spiral
      ganglion, and such cochlear damages were obviously alleviated in PPTA group.
      CONCLUSION: PPTA can protect against gentamicin-induced cochlear damage in guinea
      pigs by decreasing the protein expression of caspase-3 to inhibit cell apoptosis.

PMID- 24670444
TI  - [Effect of sufentanil preconditioning on myocardial P-Akt expression in rats
      during myocardial ischemia-reperfusion].
AB  - OBJECTIVE: To study the protective effect of sufentanil preconditioning against
      myocardial ischemia-reperfusion (I/R) injury and the role of PI3K/Akt signaling
      pathway. METHODS: Sixty male SD rats weighing 250-350 g were randomly divided
      into 5 equal groups, namely the sham-operated group, I/R group, sufentanil
      preconditioning group (Spc group), sufentanil preconditioning +PI3K inhibitor
      group (Spc+W group), and PI3K inhibitor group (W group). Myocardial I/R model was
      established by ligation of the anterior descending branch of the left coronary
      artery for 30 min followed by reperfusion for 120 min. Sufentanil was
      administered in 3 doses via the femoral vein before the occlusion, each at 1
      ug/kg infused within 5 min at a 5-min interval. In Spc+W and W groups, PI3K
      inhibitor wortmannin (15 ug/kg) was given intravenously 5 min before sufentanil
      preconditioning and 35 min before ischemia, respectively. Heart rate and mean
      arterial pressure (MAP) were continuously monitored during I/R. At the end of
      reperfusion, blood samples were obtained to determine plasma activation of CK-MB
      and LDH. Acute infarct size was measured by triphenyltetrazolium chloride
      staining, and the myocardial tissues were obtained to detect the expression of
      phosphorylated Akt using Western blotting. RESULTS: Phosphorylated Akt expression
      was significantly up-regulated in I/R and Spc groups as compared with the sham
      group, and was significantly higher in Spc group than in I/R group. After
      reperfusion, sufentanil preconditioning significantly decreased myocardial
      infarct size (P<0.01) and lowered the levels of CK-MB (P<0.01) and LDH (P<0.01)
      compared with those in the I/R group. The I/R , Spc+W and W groups showed no
      significant differences in myocardial infarct size or the levels of CK-MB and
      LDH. CONCLUSION: The protective effect of sufentanil preconditioning against
      myocardium against I/R injury in rats may involve PI3K/Akt signaling pathway
      activation.

PMID- 24670445
TI  - [Pathological and immunological changes of renal transplant rejection: report of
      56 cases].
AB  - OBJECTIVE: To investigate the pathological and immunological changes of renal
      grafts in recipients experiencing graft rejection. METHODS: The clinicopathologic
      data of 56 renal needle biopsy samples obtained from renal transplant recipients
      were analyzed retrospectively. The specimens were classified histopathologically
      according to the Banff 2009 classification system and analyzed by
      immunohistochemical labeling and immunofluorescence. RESULTS: In the 56
      recipients, 1 (1.79%) experienced hyperacute rejection, 8 (14.29%) had suspected
      acute rejection, 12 (21.43%) developed acute T-cell rejection, 6 (10.71%) had
      acute antibody-mediated rejection, 2 (3.57%) had acute T-cell rejection with
      acute antibody-mediated rejection, 12 (21.43%) had chronic active T cell-mediated
      rejection, 2 (3.57%) had chronic active antibody-mediated rejection, 2 (3.57%)
      had chronic active T cell-mediated rejection with antibody-mediated rejection, 8
      (14.29%) had non-specific interstitial fibrosis and tubular atrophy, and 3
      (5.36%) had normal graft function. The expression levels of immune markers CD3,
      CD4, CD8, CD20, GrB and perforin differed with the types of T cell-mediated graft
      rejection, and the positivity and expression levels of these markers tended to
      increased with the severity of graft rejection. The expression of C4d was
      positive in all cases with antibody-mediated graft rejection. CONCLUSIONS: The
      pathological characteristics of the renal biopsy specimens and expression levels
      of the immune markers allow timely and accurate evaluation of graft rejection
      type to provide a reliable pathological and etiological basis for clinical
      treatment and prognostic assessment.

PMID- 24670446
TI  - [Ultrasonic radio frequency analysis technique for noninvasive evaluation of
      carotid artery intima-media thickness and elasticity in patients with
      dyslipidemia].
AB  - OBJECTIVE: To assess the value of ultrasonic radio frequency analysis technique
      for noninvasively evaluation of carotid artery intima-media thickness (IMT) and
      elasticity in patients with dyslipidemia. METHODS: Radio frequency quality intima
      media thickness (RFQIMT) technique and radio frequency quality arterial stiffness
      ((RF)QAS) technique were used for measurement of IMT and pulse wave velocity
      (PWV) of the left carotid artery in 86 patients with dyslipidemia and 60 healthy
      volunteers. RESULTS: Apart from the patients' age, body mass index, systolic
      blood pressure, diastolic blood pressure, pulse pressure, total cholesterol,
      triglyceride, low density lipoprotein, high density lipoprotein, fasting blood
      glucose, IMT and PWV differed significantly between the control and case groups.
      IMT was positively correlated with PWV (r=0.521, P<0.05). In patients with
      IMT<1.0 mm (n=81), PWV differed significantly between patients with different
      number of other atherogenic risk factors (P=0.004), but IMT showed no such
      variation (P=0.079). In patients with more than 3 and those with 2 other risk
      factors, PWV increased significantly as compared with those with one risk factor
      (P=0.002). Multiple linear regression analysis showed that systolic blood
      pressure, age and fasting blood glucose were independently associated with PWV.
      CONCLUSION: Ultrasonic radio frequency analysis technique allows accurate
      measurement of IMT and arterial elasticity, and may thus become a valuable method
      for evaluating early structural and arterial functional change of the carotid
      artery.

PMID- 24670447
TI  - [Evaluation of left ventricular diastolic function by TE-e' measurement using
      dual Doppler echocardiography in coronary heart disease patients with preserved
      systolic function].
AB  - OBJECTIVE: To evaluate the accuracy of the time interval between the onset of
      early transmitral flow velocity (E) and that of early diastolic mitral annular
      velocity (e') (TE-e') measured by dual Doppler echocardiography in the diagnosis
      of diastolic dysfunction. METHODS: Seventy-seven coronary heart disease patients
      with preserved systolic function underwent a echocardiographic study. Early
      transmitral flow velocity E and early diastolic mitral annular velocity e' were
      simultaneously recorded by dual Doppler echocardiography. The E/e' and TE-e' were
      calculated and compared with the left ventricular end diastolic pressure (LVEDP),
      which was measured invasively. The validity of TE-e', E/e' and their combination
      was analyzed in estimating left ventricular dysfunction (LVEDP >=12 mmHg).
      RESULTS: The single-beat E/e' and TE-e' were correlated with the LVEDP (r=0.79
      and 0.42, respectively, P<0.001). Receiver-operating characteristic analysis
      showed that the optimal cut-off for TE-e' was 38 ms (sensitivity 54%, specificity
      79%, AUC 0.71) and that for E/e' was 9.2 (sensitivity 74%, specificity 81%, AUC
      0.87) for diagnosis of left ventricular diastolic dysfunction. The combined cut
      offs of TE-e'>=38 ms and E/e'>=9.2 had a sensitivity of 100% and a specificity of
      62% in diagnosing left ventricular diastolic dysfunction with an AUC of 0.96.
      CONCLUSION: In patients with coronary heart disease, the simultaneous recording
      of TE-e' by dual Doppler echocardiography can accurately estimate diastolic
      dysfunction, and its combination with E/e' can further improve the diagnostic
      accuracy.

PMID- 24670448
TI  - [Expression of plasma miR-106a in colorectal cancer and its clinical
      significance].
AB  - OBJECTIVE: To detect plasma miR-106a level in patients with colorectal cancer
      (CRC) and analyze its correlation to the clinicopathological features and disease
      diagnosis. METHODS: miRNA expression profiling was performed using miRNA
      microarray chip for 3 colorectal adenocarcinoma samples and matched normal
      tissues. Plasma samples was collected from 50 colorectal cancer patients for
      quantitative analysis of miR-106a using real-time RT-PCR using 47 plasma samples
      from healthy volunteer as the control. Forty plasma samples were collected from
      these patients 7 days after operation to examine the changes in miR-106a
      expression. RESULTS: miR-106a was differentially expressed in colorectal
      adenocarcinoma compared to normal tissues. The plasma levels of miR-106a
      expression were significantly higher in the cancer patients than in the healthy
      control group (P=0.012). miR-106a expression significantly decreased after the
      operation compared with its preoperative level (P<0.01), and no correlation was
      found between preoperative plasma miR-106a and the clinicopathological features
      including lymph node metastasis and TNM stage (P>0.05). miR-106a showed a
      receiver operating characteristic (ROC) curve area of 66.1%, a sensitivity of
      62.3%, and a specificity of 68.2% in discriminating colorectal cancer patients
      from the control subjects. CONCLUSION: plasma miR-106a is up-regulated in CRC
      patients, suggesting its potential value for the diagnosis of CRC.

PMID- 24670449
TI  - [Targeting microRNA-mediated suppression of vascular endothelial growth factor
      gene expression and proliferation in malignant melanoma cells in vitro].
AB  - OBJECTIVE: To explore the inhibitory effect of targeting miRNA on the expression
      of vascular endothelial growth factor (VEGF) and cell proliferation in malignant
      melanoma (MM) SKmel-28 cells. METHODS: Recombination miRNA plasmid vectors
      targeting VEGF gene were transfected into SKmel-28 cells via Lipofectamine 2000.
      The integrity of the inserted fragments was detected using colony PCR and
      sequence analysis. The expression of VEGF mRNA and protein in SKmel-28 cells was
      detected by RT-PCR and Western blotting, respectively. MTS assay was used to
      determine the inhibitory effect of a selected targeting miRNA on SKmel-28 cell
      proliferation, and the apoptosis of SKmel-28 cells was detected using flow
      cytometry. RESULTS: Transfection with the targeting miRNAs significantly down
      regulated the expressions of VEGF mRNA and protein in SKmel-28 cells (P<0.01),
      and the miRNA construct X-26-2n-1 showed the highest inhibitory effect. The miRNA
      X-26-2n-1 significantly suppressed SKmel-28 cell proliferation in a time
      dependent manner (P<0.01) and increased the early, late and overall apoptosis
      rates of the cells (P<0.01). CONCLUSION: The targeting miRNA we constructed can
      effectively suppress the cell proliferation and induce apoptosis of SKmel-28
      cells by down-regulating the expressions of VEGF gene.

PMID- 24670450
TI  - [Therapeutic effect of levetiracetam add-on treatment for frontal lobe epilepsy
      in 105 children].
AB  - OBJECTIVE: To study the changes in 24-hour video electroencephalogram (EEG) and
      epileptic attacks after levetiracetam add-on therapy in children with frontal
      lobe epilepsy and epileptiform discharges. METHODS: A prospective study was
      carried out in 105 children with the frontal lobe epilepsy who received long-term
      treatment with 1 or 2 types of antiepileptic drug but still with epileptiform
      discharges in ECG. Levetiracetam add-on therapy was administered at the initial
      daily dose of 20 mg/kg (given in 2 doses) for 2 weeks followed by an increase of
      the dose to 30 mg/kg with a maintenance dose of 30-40 mg/kg. The changes in
      seizure attacks and 24-hour video-EEG monitoring after a 6-month therapy were
      observed. RESULTS: Levetiracetam add-on therapy reduced epileptiform discharges
      in 55 children (52.3%) and resulted in significant changes in EEG (P<0.05). Of
      the 77 children with clinical seizures, complete seizure control was achieved in
      12 cases after the therapy, and the seizure attacks were reduced in 28 cases,
      showing a total response rate of 51.9%; the reduction in seizure attacks was
      positively correlated with EEG improvement (P<0.001). CONCLUSION: Levetiracetam
      add-on therapy can decrease epileptiform discharges in EEG and reduce clinical
      seizure attacks in children with frontal lobe epilepsy with only mild adverse
      reactions.

PMID- 24670451
TI  - [Screening of novel miRNAs targeting EZH2 3' untranslated region using lentivirus
      miRNAs library and their expressions in breast cancer cells and tissues].
AB  - OBJECTIVE: To screen novel miRNAs targeting EZH2 3' untranslated region (UTR) in
      recombinational MCF-7 breast cancer cells over-expressing EZH2 3' UTR and
      quantitative analyze the expressions of the screened miRNA in breast cancer cells
      and tissues. METHODS: A lentiviral library was transfected into the recombinant
      cell line MCF-7. The cells were screened with cytotoxic agents before extraction
      of the genome for amplification of the miRNA precursors using PCR. The screened
      miRNAs were identified with sequence analysis and their expressions were analyzed
      quantitatively with real-time PCR in breast cancer cells and tissues. RESULTS:
      Seven miRNAs were screened from the recombinant MCF-7 cells, namely miR-15b, miR
      16-2, miR-181b2, miR-217, miR-224, miR-329-1, and miR-487b, all of which failed
      to be predicted by bioinformatics software. Real-time PCR showed that miR-217,
      miR-329-1, and miR-487b were over-expressed in MCF-7 cells, and the expression of
      miR-15b and miR-16-2 was significantly increased in cancer tissues compared with
      the adjacent tissues (P<0.05). CONCLUSION: Novel targeted miRNAs that can not be
      predicted by bioinformatics software were successfully screened from MCF-7 breast
      cancer cells over-expressing EZH2 3' UTR. These miRNAs are expressed
      differentially between normal breast cells and breast cancer tissues.

PMID- 24670452
TI  - [Effects of emodin on IL-23/IL-17 inflammatory axis, Th17 cells and viral
      replication in mice with viral myocarditis].
AB  - OBJECTIVE: To explore the effects of emodin in myocardial protection in mice with
      viral myocarditis (VMC) and explore molecular mechanisms. METHODS: Fifty-five
      male 4-week-old BALB/c mice were randomly divided into control group (n=15),
      model group (n=20), and emodin group (n=20). The mice in model and emodin groups
      were inoculated with 0.1 ml Eagle's solution containing coxsackievirus B3
      intraperitoneally, and those in the control group were given only 0.1 ml Eagle's
      solution. From the day of inoculation, the mice in emodin group received
      intragastric administration with 0.1 ml of 3 mg/ml emodin solution once daily for
      21 consecutive days, and those in the control and model groups received 0.1 ml
      distilled water only. On day 7 after inoculation, 5 mice from each group were
      sacrificed to determine the viral titers in the cardiac tissues. All the mice
      were sacrificed on day 22 for measurement of the heart weight and
      histopathological inspection of the heart with HE staining. The mRNA and protein
      expression levels of myocardial interleukin-23 (IL-23) and interleukin-17 (IL-17)
      were detected by real-time quantitative PCR and Western blotting, respectively,
      and serum IL-23 and IL-17 levels were examined using enzyme linked immunosorbent
      assay (ELISA). Th17 cell frequencies were analyzed by flow cytometry. The
      expression levels of myocardial nuclear factor-kappaB (NF-kappaB) p65 in the
      cardiomyocyte nuclei were examined using Western blotting, and myocardial
      interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) contents
      were detected by ELISA. RESULTS: The mortality, myocardial histopathologic scores
      and virus titers in emodin group were all significantly lower than those in the
      model group (P<0.05). The heart-to-body weight ratio, myocardial IL-23 and IL-17
      expressions, serum IL-23 and IL-17 levels, Th17 cell frequencies, cardiomyocyte
      nuclear NF-kappaB p65 expression, and myocardial contents of IL-1beta, IL-6 and
      TNF-alpha were all significantly increased in the model group as compared to the
      control group (P<0.01) but reduced significantly in emodin group as compared to
      model group (P<0.05). CONCLUSION: Emodin can protect against VMC by inhibiting IL
      23/IL-17 inflammatory axis, Th17 cell proliferation and viral replication in
      mice.

PMID- 24670453
TI  - [Relationship between body mass index and outcome of in vitro fertilization and
      embryo transfer cycle in patients with endometriosis].
AB  - OBJECTIVE: To explore the relationship between body mass index (BMI) and clinical
      outcomes of in vitro fertilization and embryo transfer (IVF/ICSI-ET) cycles in
      patients with endometriosis. METHODS: We retrospectively analyzed the data of
      infertile women with endometriosis undergoing 244 IVF/ICSI-ET cycles between
      January, 2011 and August, 2012. The patients, categorized into 3 groups with mild
      endometriosis, moderate to severe endometriosis, and no endometriosis (control),
      underwent a long protocol, and the relationship of the general conditions, dose
      of gonadotropin, days of stimulation, BMI, number of oocytes retrieved and
      embryos transferred with the outcome of IVF were analyzed. RESULTS: There was
      significant difference between moderate to severe endometriosis group and the
      control group in the number of ampules, oocytes retrieved and embryos
      transferred. The patients with moderate or severe endometriosis had significantly
      lower BMI and clinical pregnancy rate than those with mild or no endometriosis.
      CONCLUSION: Endometriosis is inversely correlated with BMI, and BMI of the
      patients with endometriosis may affect the pregnancy rate of IVF cycles.

PMID- 24670454
TI  - [Effect of donor and recipient anti-MICA antibodies on early renal graft function
      following transplantation].
AB  - OBJECTIVE: To investigate the effects of donor and recipient anti-major
      histocompatibility complex class I-related chain A (MICA) antibodies on early
      renal graft function in renal transplant recipients. METHODS: Using Luminex200
      liquid chip technology, we detected anti-MICA antibodies in 26 deceased donors
      paired with 43 recipients. We divided the 43 pairs into 4 groups according to
      different donor and recipient anti-MICA antibody positivity statuses and compared
      the incidence of acute rejection (AR), serum creatinine at 1 week after
      transplantation, and renal function recovery time between the groups to assess
      the effect of donor and recipient anti-MICA antibodies on early graft function.
      RESULTS: Five of the 26 donors were positive for anti-MICA antibodies (19.2%),
      with the most common antibody being anti-MICA*019 (40%); 11 of the 43 recipients
      were positive for anti-MICA antibodies (25.6%), among which anti-MICA*018 was
      most frequently found (14.6%). AR did not occur in the only anti-MICA antibody
      positive recipient receiving an anti-MICA antibody-positive donor graft; AR
      occurred in 2 (33.3%) of the 6 anti-MICA antibody-negative recipients receiving
      anti-MICA antibody-positive donor graft, in 4 (40%) out of the 10 anti-MICA
      antibody-positive recipients receiving anti-MICA antibody-negative donor graft,
      and in 10 (38.4%) of the 26 anti-MICA antibody-negative recipients receiving anti
      MICA antibodies-negative donor graft. The incidences of AR were not significantly
      different between the groups (P>0.05), nor were serum creatinine levels or renal
      function recovery time at one week after surgery(P>0.05). CONCLUSION: Donor or
      recipient anti-MICA antibody positivity does not seem to significantly affect the
      incidence of AR or renal function recovery early after transplantation to justify
      the necessity of monitoring donor anti-MICA antibodies. But still, large-sample
      studies are needed to further investigate the potential impact of donor and
      recipient anti-MICA antibodies on the outcomes of renal transplantation.

PMID- 24670455
TI  - [Value of plasma growth differentiation factor-15 in diagnosis and evaluation of
      type 2 diabetic nephropathy].
AB  - OBJECTIVE: To detect the plasma level of growth differentiation factor-15 (GDF
      15) in patients of type 2 diabetic nephropathy and assess its value in diagnosis
      and evaluation of type 2 diabetic nephropathy. METHODS: Thirty type 2 diabetic
      patients with normoalbuminuria, 20 with microalbuminuria, and 30 with
      macroalbuminuria, diagnosed according to Mogensen's criteria, were examined for
      plasma GDF-15 level using enzyme-linked immunosorbent assay. RESULTS: The
      patients with macroalbuminuria had significantly higher plasma GDF-15 level than
      those with microalbuminuria and normoalbuminuria [1773.9 (1099.1-2357.4) pg/ml vs
      864.0 (636.1-994.3) pg/ml and 704.5 (548.8-975.8) pg/ml, respectively, P<0.01],
      and patients with microalbuminuria had higher GDF-15 level than those with
      normoalbuminuria (P>0.05). Plasma GDF-15 level was found to increase early in the
      stage of mild renal dysfunction (60<=GFR<90 ml.min(-1).1.73 m(-2)) with a median
      level of 999.5 (769.2-1372.1) pg/ml. Partial correlation analysis showed that
      plasma GDF-15 level was positively correlated with diabetic durations, mAlb, BUN
      and sCr (r=0.246, 0.493, 0.390, and 0.471, respectively, P<0.05), and negatively
      with eGFR (r=-0.438) and Alb (r=-0.397) (P<0.01). Multivariate linear regression
      analysis showed that a high plasma GDF-15 level was an independent risk factor
      for increased mAlb. In the diagnosis of renal dysfunction (eGFR<90 ml.min(
      1).1.73 m(-2)), the area under the receiver-operating characteristic curve (AUC)
      of GDF-15 was 0.801, significantly higher than that of mAlb (0.717, P<0.05). With
      the cut-off value of 733.78 pg/ml, plasma GDF-15 level had a sensitivity of 88.1%
      and a specificity of 58.1% for renal dysfunction diagnosis. CONCLUSION: In
      patients with type 2 diabetic nephropathy, plasma GDF-15 level increases with the
      Mogensen stage, and as a independent risk factor for increased mAlb, it is
      significantly correlated with mAlb and eGFR, and serves, suggesting its value in
      early diagnosis, evaluation and prediction of the outcomes of type 2 diabetic
      nephropathy.

PMID- 24670456
TI  - [Near-infrared Raman spectroscopy for diagnosis of gastric cancer].
AB  - OBJECTIVE: To establish a method for early diagnosis of gastric cancer using near
      infrared Raman spectroscopy. METHODS: A rapid near-infrared Raman system was used
      to examine the tissue specimens of pathologically confirmed gastric cancer (33
      cases), gastric precancerous lesions (27 cases), and normal gastric mucosa (45
      cases). All the specimens were obtained from 105 patients undergoing gastrectomy
      or endoscopic biopsy of suspected gastric lesions. RESULTS: High-quality Raman
      spectra ranging from 700 to 1800 cm(-1) were acquired from the gastric tissues
      within 5 s. The distribution pattern of Raman spectra in gastric cancer differed
      significantly from those of gastric precancerous lesions and normal gastric
      mucosa, particularly in the spectral ranges of 853 cm(-1), 936 cm(-1), 1003 cm(
      1), 1032 cm(-1), 1174 cm(-1), 1208 cm(-1), 1323 cm(-1), 1335 cm(-1), 1450 cm(-1),
      and 1655 cm(-1), which contained signals related to proteins, nucleic acids and
      lipids. The diagnostic decision algorithm based on the Raman peak intensity
      ratios of I1003/ I1337, I1003/I1445, I1003/I1655, and I1156/I1655 yielded
      remarkable differences in gastric cancer from gastric precancerous lesions and
      normal gastric mucosa, and the ratios were significantly higher in normal gastric
      tissues (P<0.05). The discrimination based on near-infrared Raman spectroscopy
      using PCA-LDA algorithms associated with leave- one-out and cross-validation
      method showed diagnostic sensitivities of 81.5%, 85.3%, and 100%, and
      specificities of 86.4%, 100%, and 97.4% for normal gastric mucosa, precancerous
      lesions and gastric cancer, respectively. CONCLUSIONS: near-infrared Raman
      spectroscopy in conjunction with intensity ratio algorithms shows the potential
      for noninvasive diagnosis and detection of gastric malignancy at the molecular
      level.

PMID- 24670457
TI  - [Expression of miR-146a in colon cancer and its significance].
AB  - OBJECTIVE: To investigate miR-146a expression in colonic cancer and its clinical
      implications. METHODS: Quantitative real-time PCR was employed to detect the
      levels of miR-146a expression in colonic cancer tissues, pair-matched adjacent
      normal tissues and different colonic cancer cell lines. MTT essay was used to
      evaluate the proliferation of colonic cancer SW260 cells transfected with miR
      146a mimics, and the cell cycle and apoptosis of the cells were analyzed with
      flow cytometry. RESULTS: Compared with the normal tissues, 38 of the 43 colonic
      cancer samples showed down-regulated miR-146a expression, which was associated
      with poor tumor differentiation. The expression of miR-146a in the tumor tissues
      was significantly correlated with tumor size and clinical stages. The patients
      with high miR-146a expression levels had significantly longer total survival time
      than those with low expression of miR-146a. In SW260 cell cultures, transfection
      with miR-146a mimics significantly inhibited cell growth (P<0.05) and increased
      the cell apoptosis rate (11.9% vs 5.9%) but produced no obvious effect on cell
      cycle. CONCLUSIONS: miR-146a may serve as a potential therapeutic target for
      colonic cancer for its role in inhibiting colonic cancer cell proliferation.

PMID- 24670458
TI  - [Impact of postoperative adjuvant therapy on prognosis of low-risk cervical
      cancer: analysis of 208 cases].
AB  - OBJECTIVE: To investigate the effect of adjuvant chemotherapy on the prognosis of
      patients with low-risk cervical cancer (without pelvic lymph node metastasis,
      parametrial involvement, positive surgical margin, primary tumor size > 4 cm,
      deep cervical stromal invasion, or lymph-vascular space invasion). METHODS: The
      clinical data of 208 patients with low-risk cervical cancer were studied
      retrospectively to analyze the indications of adjuvant chemotherapy and its
      relationship with tumor recurrence and the patients' survival. RESULTS: The
      median follow-up time of the cohort was 73 months. The overall tumor recurrence
      rate was 4.8% and the total 5-year survival rate of the patients was 96.0%. Sixty
      nine of the patients received adjuvant chemotherapy (Taxol+Cisplatin) after the
      operation with a median of 2.5 (2-4) courses. Univariate analysis showed that the
      histological tumor grade was significantly associated with adjuvant chemotherapy
      (P<0.001). In the 114 grade III patients, 50 received adjuvant chemotherapy as
      compared with 19 in the 94 grade I-II patients. Among the grade III patients, no
      significant differences was found in the overall survival rate (97.0% vs 95.0%)
      or tumor recurrence rate (4.0% vs 4.7%) rate between the patients with adjuvant
      chemotherapy and those without. The tumor size (2 cm or less vs >2 cm) was
      significantly associated with tumor recurrence rate (1.1% vs 7.5%, P=0.034) and
      the overall 5-year survival rate (100.0% vs 93.0%, P=0.034) in the 208 patients.
      In the 139 patients receiving only surgical treatment, the tumor recurrence and 5
      year survival rates were not significantly correlated with the histologic grade,
      age, FIGO staging, gross type, tumor size or histologic type. CONCLUSION: B There
      has been no sufficient evidence to support the prescription of postoperative
      adjuvant chemotherapy for low-risk cervical cancer based on histological grading
      of the tumor, which may not help in reducing tumor recurrence or improving the
      long-term survival of the postoperative patients.

PMID- 24670459
TI  - [Factors for predicting outcomes of liver transplantation and liver resection for
      hepatocellular carcinoma meeting Milan criteria].
AB  - OBJECTIVE: To investigate the risk factors affecting neoplasm recurrence and
      metastasis following liver transplantation (LT) and liver resection (LR) in
      patients with hepatocellular carcinoma (HCC) meeting Milan criteria. METHODS: We
      retrospectively analyzed the clinical data of 88 patients with HCC meeting Milan
      criteria undergoing LT or LR in Nanfang Hospital between January, 2006 and
      December, 2011 and compared the survival rate and recurrence-free survival rate
      between the two groups. Univariate analysis of 12 variables during peri-operative
      period was carried out to screen the risk factors affecting neoplasm recurrence
      and metastasis. RESULTS: The LT group and HR group had similar 1-, 3-, and 5-year
      survival rates (P>0.05), but the LT group showed significantly higher 1-, 3-, and
      5-year recurrence-free survival rates (P<0.05). The recurrence rate was much
      lower in LT group than in LR group (P<0.05). Multivariate analysis identified
      gender, tumor size, degree of pathological differentiation, and microvascular
      tumor embolism as independent risk factors affecting the recurrence-free survival
      rate. CONCLUSION: Patients with HCC meeting Milan criteria undergoing LT have
      longer long-term recurrence-free survival. A male patient with a greater tumor
      size, microvascular tumor embolism, and poorly differentiated carcinoma is more
      likely to develop neoplasm recurrence and metastasis following the surgery.

PMID- 24670460
TI  - [Effect of interleukin-1beta on expressions of activin A and its related factors
      in cultured endometrial stromal cells from patients with endometriosis].
AB  - OBJECTIVE: To study the effect of interleukin-1beta (IL-1beta) on the expressions
      activin A, follistatin, and cripto in cultured human endometrial stromal cells
      (HESCs) form patients with endometriosis. METHODS: Cultured HESCs were stimulated
      with 250, 500, and 750pg/ml IL-1beta, and the mRNA and protein expressions of
      activin A, follistatin, and cripto were assayed using real-time reverse
      transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay.
      RESULTS: IL-1beta treatment caused significant dose-dependent increments of the
      mRNA and protein expressions of activin A and follistatin and of the mRNA
      expression of cripto in cultured HESCs. CONCLUSION: IL-1beta can affect the
      expressions of activin A, follistatin and cripto in HESCs from patients with
      endometriosis.

PMID- 24670461
TI  - [Donations after cardiac death kidney transplantation in northwest China].
AB  - OBJECTIVE: To explore the effect of donations after cardiac death (DCD) kidney
      transplant performed in northwest China and the measures for management of
      delayed graft function (DGF). METHODS: In the period of 2011-2013, a total of 51
      families of DCD donor gave their consent to organ donation by signing the
      informed consent with the help by a Red Cross Organization (ROC) coordinator, and
      102 kidneys were retrieved by organ procurement organization (OPO) teams. Ninety
      four operations of renal transplantation were carried out in our hospital. All
      the patients were followed-up and based on the occurrence of DGF after
      transplantation, they were divided into DGF group and non-DGF group for
      comparative studies. RESULTS: The success rate of donation after cardiac death
      was 29.3%, and the incidence of post-transplantation DGF was 27.7%. The 1-year
      human/kidney survival rate was 98.9%/95.7%. Within six months after the
      transplant, the values of eGFR in DGF group were significantly lower and serum
      creatinine significantly higher than those in non-DGF group (P<0.05), but no
      significant differences were found between the two groups thereafter (P>0.05).
      The occurrence of DGF in LifePort mechanical perfusion cohorts was significantly
      lower than that in the simple cold preservation group (21.5% vs. 41.4%, P<0.05).
      CONCLUSION: The overall effect of DCD kidney transplant is good despite a high
      incidence of early DGF, and we recommend the use of low-temperature mechanical
      perfusion for storage and transportation of DCD donor kidney.

PMID- 24670462
TI  - [Detection of serum food specific antibodies of 6 common foods in patients with
      IgA nephropathy].
AB  - OBJECTIVE: To explore the relationship between the major allergens of 6 common
      allergic foods and IgA nephropathy. METHODS: A sensitive sandwich enzyme-linked
      immunosorbent assay (ELISA) was used to detect the serum levels of food-specific
      IgA1, IgG and IgE in 31 patients with IgA nephropathy and 80 healthy volunteers.
      All the patients were examined for a history of food allergy using a
      questionnaire. RESULTS: Serum levels of IgA1 and IgG against the major allergens
      of the 6 common allergic foods were significantly higher in patients with IgA
      nephropathy than in healthy volunteers (P<0.05). There was no detectable food
      specific IgE antibodies in the two groups. No patients had a clear history of
      food allergy. All the patients with increased IgG levels specific to 4 or more
      foods simultaneously had proteinuria. CONCLUSIONS: Some foods especially the
      highly allergic ones may participate in the pathogenesis and progression of IgA
      nephropathy.

PMID- 24670463
TI  - [Clinical significance of MMP2 overexpression in endometrial adenocarcinoma].
AB  - OBJECTIVE: To explore the expression of MMP2 and its correlation with the
      clinical features and prognosis of endometrial adenocarcinoma. METHODS: We
      collected paraffin-embedded samples from 81 patients with endometrial
      adenocarcinoma aged 32 to 80 years to examine the expression of MMP2 using
      immunohistochemistry. The correlation of MMP2 expression with the clinical
      characteristics and prognosis of the patients was analyzed. RESULTS: MMP2 protein
      was expressed in the cytoplasm of the tumor cells. MMP2 over-expression was
      negatively correlated with tumor differentiation (P=0.015) and prognosis
      (P=0.041) of endometrial adenocarcinoma. CONCLUSION: MMP2 over-expression is a
      potential malignant biomarker in endometrial adenocarcinoma.

PMID- 24670464
TI  - [Effect of antibacterial peptide LL-37 on the integrity of Acinetobacter
      baumannii biofilm].
AB  - OBJECTIVE: To investigate the effect of antibacterial peptide LL-37 on the
      integrity of Acinetobacter baumannii biofilm. METHODS: A model of Acinetobacter
      baumannii biofilm in vitro was constructed by plates and crystal violet staining
      method, and the minimal inhibitory concentration of LL-37 was determined by broth
      dilution. The biofilm morphology was observed by scanning electron microscopy and
      biofilm formation was analyzed by the crystal violet staining of the adherent
      biofilm in the presence of antibacterial peptide LL-37. RESULTS: In the
      Acinetobacter baumannii biofilm model, the minimal inhibitory concentration of LL
      37 was 64 ug/ml; LL-37 caused structural damage of the biofilm at a low
      concentration of 2.5 ug/ml. The biofilm was decreased gradually as the
      concentration of LL-37 increased. CONCLUSION: LL-37 even at a concentration far
      below its minimal inhibitory concentration can cause structural damage of
      Acinetobacter baumannii biofilm in vitro.

PMID- 24670465
TI  - [Effect of casein osphopeptide-amorphous calcium phosphate solution in preventing
      enamel demineralization].
AB  - OBJECTIVE: To evaluate the effects of casein osphopeptide-amorphous calcium
      phosphate (CPP-ACP) in preventing enamel demineralization. METHODS: Enamel blocks
      were prepared from premolars extracted from orthodontic patients. The specimens
      were treated for 30 min daily for 7 days with one of the following agents:
      deionized water (negative control), CPP-ACP paste, and NaF solutions (positive
      controls) (0.2% and 2%). After the treatments, the specimens were immersed in a
      demineralizing solution (pH 4.5) for 7 days. The morphology and depth of the
      lesion were observed using scanning electron microscopy, and the content of Ca,
      P, Mg in the demineralized enamel was measured by electron probe micro-analyzer.
      RESULTS: The demineralization rates in all the treatment groups were
      significantly smaller than those in the control group after 7 days of
      demineralization. CONCLUSION: The application of CPP-ACP to the enamel surfaces
      can inhibit enamel demineralization with an equivalent effect to 0.2% NaF.

PMID- 24670466
TI  - [Feasibility of monitoring clopidogrel resistance with flow cytometric analysis
      of platelet vasodilator stimulated phosphoprotein phosphorylation].
AB  - OBJECTIVE: To evaluate the feasibility of monitoring clopidogrel resistance with
      flow cytometric analysis of platelet vasodilator stimulated phosphoprotein (VASP)
      phosphorylation. METHODS: Twenty patients with coronary heart disease (CHD) and
      17 healthy volunteers were examined for platelet aggregation rate and
      phosphorylation of VASP (calculated as platelet reactivity index, PRI) using
      traditional optical nephelometry and flow cytometry before and after concurrent
      therapy of clopidogrel and aspirin. RESULTS: No significant differences were
      found in PRI between CHD group and healthy control group [(89.45?5.22)% vs
      (86.58?4.35)%] before treatment. The PRI in CHD group was significantly lowered
      after treatment to (67.66?19.77)% (P<0.05). Clopidogrel resistance was found in 6
      (30%) cases in CHD group by flow cytometric analysis, which showed a higher
      sensitivity than optical nephelometry (10%). CONCLUSION: Flow cytometric analysis
      of VASP phosphorylation is a more reliable test to specifically evaluate
      clopidogrel resistance.

PMID- 24670467
TI  - [Effect of autologous drained blood reinfusion on hidden blood loss and limb
      swelling following rivaroxaban anticoagulation for primary total hip
      arthroplasty].
AB  - OBJECTIVE: To study the effect of autologous drained blood reinfusion on hidden
      blood loss and limb swelling following rivaroxaban anticoagulation for primary
      total hip arthroplasty. METHODS: From May, 2011 to October, 2012, 98 patients
      undergoing primary unilateral total hip arthroplasty received rivaroxaban therapy
      for prevention of deep venous thrombosis (DVT). Forty-five of the patients used a
      drained blood reinfusion device (group A) and 53 patients did not (group B).
      Hidden blood loss and the maximal changes of postoperative circumferential length
      of the mid-thigh were measured and compared between the two groups. RESULTS: The
      mean total blood loss, the hidden blood loss, and the maximal changes of
      postoperative thigh circumference were 1591.1?337.3 ml, 1591.1?337.3 ml, and
      5.1?2.8 cm in group A, as compared to 1374.5?317.3 ml, 467?96.8 ml, 3.9?1.4 cm in
      group B, respectively. The two groups showed a significant difference in the
      maximal changes of postoperative mid-thigh circumference (P<0.01) but not in
      hidden blood loss (P>0.05). CONCLUSION: Reinfusion of autologous drained blood
      does not affect hidden blood loss but can increase limb swelling following
      primary total hip arthroplasty with rivaroxaban anticoagulation.

PMID- 24670468
TI  - A new species of mesonivirus from the Northern Territory, Australia.
AB  - Here we describe Casuarina virus (CASV), a new virus in the family Mesoniviridae.
      This is the first report of a mesonivirus in Australia, which extends the
      geographical range of this virus family to 3 continents. The virus was isolated
      in 2010 from Coquillettidia xanthogaster mosquitoes during surveillance in the
      suburbs of Darwin, the capital of the Northern Territory. Cryo-electron
      microscopy of the CASV virions revealed spherical particles of 65 nm in size with
      large club-shaped projections of approximately 15 nm in length. The new virus was
      most closely related to Alphamesonivirus 1, the only currently recognized species
      in the family. In 2013 a further 5 putative new mesonivirus species were
      described: Hana, Meno, Nse, Moumo and Dak Nong viruses. The evolutionary distance
      between CASV and two of its closest relatives, Cavally and Hana viruses (Jones
      Taylor-Thornton distance of 0.151 and 0.224, respectively), along with its
      isolation from a different genus of mosquitoes captured on a separate continent
      indicate that CASV is a new species. 

PMID- 24670469
TI  - Long-term cognitive correlates of traumatic brain injury across adulthood and
      interactions with APOE genotype, sex, and age cohorts.
AB  - There is continuing debate about long-term effects of brain injury. We examined a
      range of traumatic brain injury (TBI) variables (TBI history, severity,
      frequency, and age of injury) as predictors of cognitive outcome over 8 years in
      an adult population, and interactions with apolipoprotein E (APOE) genotype, sex,
      and age cohorts. Three randomly sampled age cohorts (20-24, 40-44, 60-64 years at
      baseline; N = 6333) were each evaluated three times over 8 years. TBI variables,
      based on self-report, were separately modeled as predictors of cognitive
      performance using linear mixed effects models. TBI predicted longitudinal
      cognitive decline in all three age groups. APOE epsilon4 + genotypes in the young
      and middle-aged groups predicted lower baseline cognitive performance in the
      context of TBI. Baseline cognitive performance was better for young females than
      males but this pattern reversed in middle age and old age. The findings suggest
      TBI history is associated with long-term cognitive impairment and decline across
      the adult lifespan. A role for APOE genotype was apparent in the younger cohorts
      but there was no evidence that it is associated with impairment in early old age.
      The effect of sex and TBI on cognition varied with age cohort, consistent with a
      proposed neuroprotective role for estrogen.

PMID- 24670473
TI  - Early diagnosis of Irkut virus infection using magnetic bead-based serum peptide
      profiling by MALDI-TOF MS in a mouse model.
AB  - Early diagnosis is important for the prompt post-exposure prophylaxis of
      lyssavirus infections. To diagnose Irkut virus (IRKV) infection during incubation
      in mice, a novel method using magnetic bead-based serum peptide profiling by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) has been established. For this test, serum peptides were
      concentrated by adsorption to and elution from the magnetic bead-based weak
      cation ion exchanger. Mass spectrograms obtained by MALDI-TOF MS were analyzed
      using ClinProTools bioinformatics software. Construction of the diagnostic model
      was performed using serum samples from mice infected with IRKV and rabies virus
      (RABV) BD06, Flury-LEP, and SRV9 (as controls). The method accurately diagnosed
      sera 2, 4 and 8 days after IRKV and RABV infections. The sensitivity,
      specificity, and total accuracy of diagnosis were 86.7%, 95.2%, and 92.9%,
      respectively. However, IRKV could not be differentiated from RABV 1 day after
      infection. The results of the present study indicate that serum peptide profiling
      by MALDI-TOF MS is a promising technique for the early clinical diagnosis of
      lyssavirus infections and needs to be further tested in humans and farm animals. 

PMID- 24670474
TI  - Potential roles of bone morphogenetic protein (BMP)-9 in human liver diseases.
AB  - Bone morphogenetic proteins (BMP-2 to BMP-15) belong to the Transforming Growth
      Factor (TGF)-beta superfamily and, besides their well-documented roles during
      embryogenesis and bone formation, some of them have recently been described to be
      involved in the pathogenesis of different organs, including the liver. The role
      of BMPs in liver damage responses including hepatocellular carcinoma (HCC)
      development has only begun to be addressed and strong evidence supports the
      concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also
      termed Growth and Differentiation Factor (GDF)-2) represents the most recently
      discovered member of the BMP family. We have previously demonstrated that in HCC
      patient samples BMP-9 expression was positively associated with the tumor seize
      ("T stage") and that it enhanced cell migration and induced epithelial to
      mesenchymal transition (EMT) in HCC cells in vitro. In another study we recently
      found that BMP-9 promotes growth in HCC cells, but not in non-transformed
      hepatocytes. Published as well as unpublished results obtained with primary
      hepatocytes support the concept of a dual function of BMP-9 in the liver: while
      in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and
      inhibits proliferation, in HCC cells it induces cell growth and the acquisition
      of a migratory phenotype. In this review article we summarize current knowledge
      about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC
      development and progression, that may provide new clues for a better
      understanding of the contribution of BMP-signaling to chronic liver diseases. 

PMID- 24670475
TI  - Terminal protection of small molecule-linked DNA for small molecule-protein
      interaction assays.
AB  - Methods for the detection of specific interactions between diverse proteins and
      various small-molecule ligands are of significant importance in understanding the
      mechanisms of many critical physiological processes of organisms. The techniques
      also represent a major avenue to drug screening, molecular diagnostics, and
      public safety monitoring. Terminal protection assay of small molecule-linked DNA
      is a demonstrated novel methodology which has exhibited great potential for the
      development of simple, sensitive, specific and high-throughput methods for the
      detection of small molecule-protein interactions. Herein, we review the basic
      principle of terminal protection assay, the development of associated methods,
      and the signal amplification strategies adopted for performance improving in
      small molecule-protein interaction assay. 

PMID- 24670476
TI  - Impact of inhaled nitric oxide on the sulfatide profile of neonatal rat brain
      studied by TOF-SIMS imaging.
AB  - Despite advances in neonatal intensive care leading to an increased survival rate
      in preterm infants, brain lesions and subsequent neurological handicaps following
      preterm birth remain a critical issue. To prevent brain injury and/or enhance
      repair, one of the most promising therapies investigated in preclinical models is
      inhaled nitric oxide (iNO). We have assessed the effect of this therapy on brain
      lipid content in air- and iNO-exposed rat pups by mass spectrometry imaging using
      a time-of-flight secondary ion mass spectrometry (TOF-SIMS) method. This
      technique was used to map the variations in lipid composition of the rat brain
      and, particularly, of the white matter. Triplicate analysis showed a significant
      increase of sulfatides (25%-50%) in the white matter on Day 10 of life in iNO
      exposed animals from Day 0-7 of life. These robust, repeatable and semi
      quantitative data demonstrate a potent effect of iNO at the molecular level. 

PMID- 24670477
TI  - Solar light photocatalytic CO2 reduction: general considerations and selected
      bench-mark photocatalysts.
AB  - The reduction of carbon dioxide to useful chemicals has received a great deal of
      attention as an alternative to the depletion of fossil resources without altering
      the atmospheric CO2 balance. As the chemical reduction of CO2 is energetically
      uphill due to its remarkable thermodynamic stability, this process requires a
      significant transfer of energy. Achievements in the fields of photocatalysis
      during the last decade sparked increased interest in the possibility of using
      sunlight to reduce CO2. In this review we discuss some general features
      associated with the photocatalytic reduction of CO2 for the production of solar
      fuels, with considerations to be taken into account of the photocatalyst design,
      of the limitations arising from the lack of visible light response of titania, of
      the use of co-catalysts to overcome this shortcoming, together with several
      strategies that have been applied to enhance the photocatalytic efficiency of CO2
      reduction. The aim is not to provide an exhaustive review of the area, but to
      present general aspects to be considered, and then to outline which are currently
      the most efficient photocatalytic systems. 

PMID- 24670478
TI  - Endothelialization of novel magnesium-rare earth alloys with fluoride and
      collagen coating.
AB  - Magnesium (Mg) alloys are promising scaffolds for the next generation of
      cardiovascular stents because of their better biocompatibility and biodegradation
      compared to traditional metals. However, insufficient mechanical strength and
      high degradation rate are still the two main limitations for Mg materials.
      Hydrofluoric acid (HF) treatment and collagen coating were used in this research
      to improve the endothelialization of two rare earth-based Mg alloys. Results
      demonstrated that a nanoporous film structure of fluoride with thickness of ~20
      um was formed on the Mg material surface, which improved the corrosion
      resistance. Primary human coronary artery endothelial cells (HCAECs) had much
      better attachment, spreading, growth and proliferation (the process of
      endothelialization) on HF-treated Mg materials compared to bare- or collagen
      coated ones. 

PMID- 24670479
TI  - All-nanoparticle self-assembly ZnO/TiO2 heterojunction thin films with remarkably
      enhanced photoelectrochemical activity.
AB  - The multilaminated ZnO/TiO2 heterojunction films were successfully deposited on
      conductive substrates including fluorine-doped tin oxide (FTO) glass and flexible
      indium tin oxide coated poly(ethylene terephthalate) via the layer-by-layer (LBL)
      self assembly method from the oxide colloids without using any polyelectrolytes.
      The positively charged ZnO nanoparticles and the negatively charged TiO2
      nanoparticles were directly used as the components in the consecutive deposition
      process to prepare the heterojunction thin films by varying the thicknesses.
      Moreover, the crystal growth of both oxides could be efficiently inhibited by the
      good connection between ZnO and TiO2 nanoparticles even after calcination at 500 
      degrees C, especially for ZnO which was able to keep the crystallite size under
      25 nm. The as-prepared films were used as the working electrodes in the three
      electrode photoelectrochemical cells. Because the well-contacted nanoscale
      heterojunctions were formed during the LBL self-assembling process, the ZnO/TiO2
      all-nanoparticle films deposited on both substrates showed remarkably enhanced
      photoelectrochemical properties compared to that of the well-established TiO2 LBL
      thin films with similar thicknesses. The photocurrent response collected from the
      ZnO/TiO2 electrode on the FTO glass substrate was about five times higher than
      that collected from the TiO2 electrode. Owing to the absence of the insulating
      layer of dried polyelectrolytes, the ZnO/TiO2 all-nanoparticle heterojunction
      films were expected to be used in the photoelectrochemical device before
      calcination. 

PMID- 24670481
TI  - Evaluating new biomarkers for acute kidney injury: putting the horse before the
      cart.

PMID- 24670480
TI  - Divalent metal ions enhance DOPAL-induced oligomerization of alpha-synuclein.
AB  - Parkinson disease (PD) features profound striatal dopamine depletion and Lewy
      bodies containing abundant precipitated alpha-synuclein. Mechanisms linking alpha
      synucleinopathy with the death of dopamine neurons remain incompletely
      understood. One such link may be 3,4-dihydroxyphenylacetaldehyde (DOPAL). All of
      the intra-neuronal metabolism of dopamine passes through DOPAL, which is toxic.
      DOPAL also potently oligomerizes alpha-synuclein and alpha-synuclein oligomers
      are thought to be pathogenic in PD. Another implicated factor in PD pathogenesis
      is metal ions, and alpha-synuclein contains binding sites for these ions. In this
      study we tested whether divalent metal ions augment DOPAL-induced oligomerization
      of alpha-synuclein in cell-free system and in PC12 cells conditionally over
      expressing alpha-synuclein. Incubation with divalent metal ions augmented DOPAL
      induced oligomerization of alpha-synuclein (Cu(2+)>Fe(2+)>Mn(2+)), whereas
      monovalent Cu(1+) and trivalent Fe(3+) were without effect. Other dopamine
      metabolites, dopamine itself, and metal ions alone or in combination with
      dopamine, also had no effect. Antioxidant treatment with ascorbic acid and
      divalent cation chelation with EDTA attenuated the augmentation by Cu(2+) of
      DOPAL-induced alpha-synuclein oligomerization. Incubation of PC12 cells with L
      DOPA markedly increased intracellular DOPAL content and promoted alpha-synuclein
      dimerization. Co-incubation with Cu(2+) amplified (p=0.01), while monoamine
      oxidase inhibition prevented, L-DOPA-related dimerization of alpha-synuclein
      (p=0.01). We conclude that divalent metal ions augment DOPAL-induced
      oligomerization of alpha-synuclein. Drugs that interfere with this interaction
      might constitute a novel approach for future treatment or prevention approaches. 

PMID- 24670482
TI  - Ischemic and hemorrhagic stroke: high incidence in hemodialysis and peritoneal
      dialysis patients.

PMID- 24670483
TI  - A new clinical prediction tool for 5-year kidney transplant outcome.

PMID- 24670484
TI  - Quiz page: a familial glomerulopathy.

PMID- 24670485
TI  - Graphene oxide as an anaerobic membrane scaffold for the enhancement of B.
      adolescentis proliferation and antagonistic effects against pathogens E. coli and
      S. aureus.
AB  - The impact of the gut microbiota on human health is widely perceived as the most
      exciting advancement in biomedicine. The gut microbiota has been known to play a
      crucial role in defining states of human health and diseases, and thus becomes a
      potential new territory for drug targeting. Herein, graphene oxide (GO)
      interaction with five common human gut bacteria, B. adolescentis, L. acidophilus,
      E. coli, E. faecalis, and S. aureus, was studied. It was shown that, in bacterial
      media, GO sheets were able to form effective, anaerobic membrane scaffolds that
      enhanced the antagonistic activity of B. adolescentis against the pathogens E.
      coli andS. aureus. Data obtained using bacterial growth measurements, colony
      counting and 16S rRNA gene sequencing consistently indicated that GO sheets
      promoted proliferation of gut bacteria, particularly for B. adolescentis.
      Scanning electron microscopy, atomic force microscopy images, and membrane
      potential measurements showed that cell membranes maintained their integrity and
      that no observable variations in cell morphology were induced after interaction
      with GO sheets, indicating good biocompatibility of GO. These results suggest the
      possibility of using GO sheets as efficient drug carriers in therapeutic
      applications to treat diseases related to the gut microbiota. 

PMID- 24670486
TI  - An electronic version of the PDQ-39: acceptability to respondents and assessment
      of alternative response formats.
AB  - BACKGROUND: The PDQ-39 is the most thoroughly validated and widely used self
      report instrument for the assessment of health-related quality of life in people
      with Parkinson's (PwP). Given the breadth of its use and increasing emphasis on
      electronic data capture, there may be significant benefit in validating an
      electronic version of the PDQ-39. OBJECTIVE: Firstly, to migrate the paper-based
      version of the PDQ-39 to a computer based platform and assess its usability and
      acceptability to respondents. Secondly, to investigate the impact of implementing
      non-response options on response rates and data completeness. METHODS: Six PwP
      participated in cognitive interviews in order to assess the usability and
      acceptability of the electronic version of the PDQ-39, the ePDQ. This was
      followed by an online survey of 129 PwP, randomly assigned to one of two groups;
      one required to provide a response to every item and one with the option to skip
      any item they did not wish to answer. RESULTS: Cognitive interviews indicated
      that the ePDQ is acceptable to PwP, with positive feedback regarding layout,
      features and functionality. 125 PwP fully completed the ePDQ. Following
      randomization 60 participants completed the forced response ePDQ and 65 completed
      the non-forced version. Response rates of 98.4% were achieved for the forced
      response ePDQ and 95.6% for the non-forced. Missing value analyses calculated
      levels of missing data at below 5% in the non-forced sample. CONCLUSIONS: The
      ePDQ is user-friendly and acceptable to respondents. Additionally, there appears
      little difference when implementing non-response options on response rates and
      data completeness.

PMID- 24670487
TI  - Cortical mechanisms of mirror activation during maximal and submaximal finger
      contractions in Parkinson's disease.
AB  - BACKGROUND: Mirror movements are often reported in the early stages of
      Parkinson's disease (PD) and have been attributed to bilateral activation of the
      primary motor cortex; however, the precise cortical mechanisms are still unclear.
      Subclinical mirror activation (MA) that accompanies mirror movement has also been
      reported in healthy aging adults. OBJECTIVE: To characterize mirror activation
      and determine the cortical mechanisms of MA in individuals with PD who
      demonstrate mirror movements. HYPOTHESIS: 5 Hz rTMS to the supplementary motor
      area (SMA) will reduce MA by increasing interhemispheric inhibition (IHI) of the
      ipsilateral motor cortex. METHODS: MA was assessed using surface electromyography
      during maximal and submaximal unimanual contractions of the first dorsal
      interosseous in 7 individuals with PD with mirror movements (PD-MM: 70.9 +/- 13.9
      years; UPDRS III: 28.0 +/- 8.2), 7 individuals with PD without mirror movements
      (PD-NM: 71 +/- 10.1 years; UPDRS III: 27.8 +/- 6.7) and 7 healthy controls (74.4
      +/- 6.0 years). IHI of the ipsilateral motor cortex was assessed using paired
      pulse transcranial magnetic stimulation. RESULTS: MA was enhanced in both PD
      groups during submaximal contractions, with the latest onset of activation in PD
      NM. Ipsilateral motor cortex excitability was the highest in PDMM; however, IHI
      did not differ between PD and controls. 5 Hz rTMS to the SMA reduced IHI in PD
      NM; however, did not affect MA. CONCLUSIONS: IHI may not be the sole contributor
      to the expression of overt mirror movements in PD. Expression of overt mirror
      movement may be due to the combination of enhanced ipsilateral motor cortex
      excitability and an earlier onset of electromyographic activation in the mirror
      hand (mirror activation) in PDMM.

PMID- 24670488
TI  - The UK National Tracheostomy Safety Project and the role of speech and language
      therapists.
AB  - PURPOSE OF REVIEW: Tracheostomy care is evolving, with the majority of procedures
      now performed percutaneously to facilitate weaning from mechanical ventilation in
      the critically ill. Traditional surgical indications remain, but surgical
      tracheostomies are increasingly performed in more complex patients and
      procedures. This brings unique challenges for the multidisciplinary professional
      team in which speech and language therapists (SLTs) have a key role. RECENT
      FINDINGS: Reviews of tracheostomy-related critical incidents have identified
      recurrent themes associated with adverse outcomes for this high-risk population.
      Recent research has highlighted the impact of tracheostomy on communication and
      swallowing, along with the contribution of SLTs to the multidisciplinary
      professional team, prompting new guidance for SLTs. The UK National Tracheostomy
      Safety Project has developed educational and practical resources that have been
      shown to improve care. Similar approaches from around the world led to the newly
      formed Global Tracheostomy Collaborative. SUMMARY: Patients with tracheostomies
      can benefit from a co-ordinated, truly multidisciplinary approach to care. SLT
      specific expertise in assessing and managing communication and swallowing needs
      is a vital part of this process.

PMID- 24670489
TI  - Managing dysphonia in occupational voice users.
AB  - PURPOSE OF REVIEW: Recent advances with regard to occupational voice disorders
      are highlighted with emphasis on issues warranting consideration when assessing,
      training, and treating professional voice users. RECENT FINDINGS: Findings
      include the many particularities between the various categories of professional
      voice users, the concept that the environment plays a major role in occupational
      voice disorders, and that biopsychosocial influences should be analyzed on an
      individual basis. Assessment via self-evaluation protocols to quantify the impact
      of these disorders is mandatory as a component of an evaluation and to document
      treatment outcomes. Discomfort or odynophonia has evolved as a critical symptom
      in this population. Clinical trials are limited and the complexity of the
      environment may be a limitation in experiment design. SUMMARY: This review
      reinforced the need for large population studies of professional voice users; new
      data highlighted important factors specific to each group of voice users.
      Interventions directed at student teachers are necessities to not only improving
      the quality of future professionals, but also to avoid the frustration and
      limitations associated with chronic voice problems. The causative relationship
      between the work environment and voice disorders has not yet been established.
      Randomized controlled trials are lacking and must be a focus to enhance treatment
      paradigms for this population.

PMID- 24670490
TI  - Differential effects of neonatal maternal separation on the expression of
      neurotrophic factors in rat brain. II: Regional differences in the cerebellum
      versus the cerebral cortex.
AB  - This study was conducted in order to examine the effects of early postnatal
      maternal separation stress on the age-dependent fluctuations in the expression
      levels of neurotrophic factor ligands and receptors in the developing cerebellum.
      Wistar rats were separated from their mothers for 3 h each day during postnatal
      days (PND) 10 to 15. The expression level of mRNA for brain-derived neurotrophic
      factor (BDNF), tyrosine kinase receptor B (TrkB), insulin-like growth factor-1
      (IGF-1), and type-1 IGF receptor (IGF-1R) were evaluated in the cerebellum on
      PND16, 20, 30, and 60 with real-time RT-PCR. The mRNA levels of cerebellar BDNF
      in maternally separated rats were increased on PND16, while the other variables
      showed no significant alterations at any of the time points examined. However,
      the effects of an identical maternal separation on the cerebral cortex were
      previously reported to be completely different. These results indicate regional
      differences in the responses of neurotrophic factor ligands/receptors between the
      cerebellum and cerebral cortex. Given that neurotrophic factors play important
      roles in brain development, alterations in these factors may interrupt normal
      brain development and ultimately, lead to functional disruptions. 

PMID- 24670491
TI  - Expression of carbonic anhydrase in the fetal eye and extra-ocular tissues.
AB  - Carbonic anhydrases (CAs) plays a critical functional role in the ciliary body
      and retina for maintenance of microenvironment. With immunohistochemistry using
      orbital contents from 8 human fetuses (12-16 weeks of gestation), we examined
      expressions of CAs isozymes-1, 2, 3, 6, 7 9 and 12 and found strong reactivity of
      CA9 in extra-ocular fibrous tissues in the anterior and posterior eyes. CA9 is
      known to express in the fetal joint cartilage to maintain pH against hypoxia:
      actually, in the present specimens, the SO pulley and its tendon was strongly
      positive for CA9. The CA9-positive anterior fibrous tissues were positive for
      smooth muscle actin and connected the orbital aspect of the 4 rectus muscle with
      the palpebral conjunctiva, whereas the posterior tissue was negative for smooth
      muscle actin and corresponded to the lateral insertion tendon of the orbitalis
      muscle. The anterior CA9-positve tissues seemed to correspond to the primitive
      form of the sleeve and pulley system. Any of matrix substances (collagen types I
      and II, aggrecan, versican, fibronectin, tenascin and hyaluronan) displayed a
      distribution pattern specific for the CA9-positive fibrous tissues. Therefore,
      whether or not CA9 was positive in the fibrous tissue seemed not to depend on the
      tissue components such as the extracellular matrix and intermediate filaments but
      to suggest a stressful condition such as hypoxia, unsuitable base balance and/or
      under mechanical stress. 

PMID- 24670492
TI  - Secretion-related structures of hypothalamo-hypophysial terminals in the rat
      posterior pituitary.
AB  - Hypothalamic terminals were investigated in the rat posterior pituitary (PP).
      Injection of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP)
      and co-injection of WGA-HRP with Rab3A-siRNA were made into the hypothalamus,
      respectively. Additional injection of WGA-HRP was made into the hypothalamus in
      the animals exposed to ethanol. These injections resulted in heavy labeling of
      fibers exclusively confined to the PP. Ultrastructural observations showed
      terminals, fibers, pituicytes, capillaries and vascular spaces in the PP.
      Although the majority of terminals were observed to contain large dense core
      vesicles (LDCVs) and HRP-reaction products (HRP-RPs), exocytosis of LDCVs in
      close proximity to cell membrane was not found. Interestingly, a few terminals
      showed alteration of cell membrane called "apocrine-like structure" containing
      LDCV and RP. The narrow neck portion of the structure gave the appearance that it
      may have been in some stage of separating from terminals. Other remarkable
      feature was that terminals occasionally reveal the structure of "leakage" of RP
      discharged into vascular spaces crossing cell membrane. Such hormone-releasing
      mechanism might be involved in one of "diacrine-like secretion". In the present
      study secretion-related structures of hypothalamic terminals in the PP are quite
      different from normal vesicular exocytosis. 

PMID- 24670494
TI  - Why is feedback so difficult?

PMID- 24670495
TI  - [Re: In praise of Grandgarden].

PMID- 24670496
TI  - [Re: Health city].

PMID- 24670497
TI  - [Re: Excessive belief in suicide risk assessments?].

PMID- 24670498
TI  - [Re: Excessive belief in suicide risk assessments?].

PMID- 24670499
TI  - [J. Hagen and colleagues reply].

PMID- 24670503
TI  - [Re: Tattoo Ink--an unknown health hazard?].

PMID- 24670504
TI  - [G.L. Gunnarsson and colleagues reply].

PMID- 24670505
TI  - [Chiropractic education in Norway now!].

PMID- 24670506
TI  - [Generic prescription of drugs in hospitals].

PMID- 24670509
TI  - Unnatural deaths among drug abusers.
AB  - BACKGROUND: Deaths caused by drug abuse, in which the cause of death is
      intoxication, so-called overdose deaths, are regularly reported and studied.
      Other deaths related to drug abuse have been less frequently studied. We wished
      to investigate the prevalence and characteristics of unnatural deaths in persons
      in whom drugs were detected in blood samples taken at autopsy. MATERIAL AND
      METHOD: A total of 1,338 forensic autopsy reports from Southern Norway for the
      years 2000-2005, in which there were positive drug findings in post mortem blood,
      were aged 20-59 years and had an unnatural manner of death (accident, suicide,
      homicide) were investigated. Gender, age, cause of death, manner of death,
      circumstances and police district were recorded. RESULTS: The mean age of those
      included in the study was 34 years, and 81% of them were men. Of all the deaths
      investigated, 998 of the deceased were in the age group 20-39 years, and 322
      deaths were due to accidents other than intoxication (most frequently traffic
      related), suicide or homicide. The remaining deaths were accidental intoxications
      (i.e. intoxications not suspected to be suicides, and which primarily account for
      the official "overdose statistics"). The proportion of women and the
      circumstances varied according to the manner of death. INTERPRETATION: Unnatural
      deaths that occur during drug use but are not accidental poisonings are not
      included in the regular "overdose statistics". These deaths account for a
      significant proportion, and are in all likelihood being underreported. They are
      somewhat different from the accidental poisonings in terms of their gender
      distribution and circumstances.

PMID- 24670510
TI  - [The polypill as cardiovascular prophylactic: clinical trials].
AB  - BACKGROUND: Cardiovascular disease dominates globally as the most common cause of
      death. This challenge may be countered by employing a combination pill (the
      "polypill") for prophylaxis by everybody above a certain age. The polypill
      normally contains two to three low-dose antihypertensives, a statin and aspirin.
      Clinical trials with the polypill are reviewed. METHOD: The databases PubMed and
      ClinicalTrials.gov were accessed for published, ongoing and planned randomised
      clinical trials with a polypill, and studies available per June 2013 were
      identified and evaluated. RESULTS: Six randomised clinical trials with different
      variations of a polypill have been published. In these, the polypill has been
      compared either with placebo (n = 3) or other cardiovascularly active
      pharmacotherapeutic strategies (n = 3). So far, no data on hard endpoints such as
      morbidity and mortality are available. On the basis of reductions in blood
      pressure and cholesterol levels, estimated risk reductions for ischemic heart
      disease and stroke were in the 33-72% and 21-64% ranges, respectively.
      INTERPRETATION: Additional studies of longer duration and with larger numbers of
      patients are required to assess the polypill's proposed effects on cardiovascular
      morbidity and mortality, as well as safety issues.

PMID- 24670511
TI  - [When the brain goes up in smoke].

PMID- 24670512
TI  - [A kidney transplant lymphoma patient starts coughing].

PMID- 24670513
TI  - [The polypill--an alternative concept in cardiovascular prophylaxis].

PMID- 24670514
TI  - [Norwegian translation of HHHFNC and HFNC].

PMID- 24670517
TI  - Contextualising women's mental distress and coping strategies in the time of
      AIDS: a rural South African case study.
AB  - Increasing attention is paid to impacts of HIV/AIDS on women's mental health,
      often framed by decontextualized psychiatric understandings of emotional distress
      and treatment. We contribute to the small qualitative literature extending these
      findings through exploring HIV/AIDS--affected women's own accounts of their
      distress-focusing on the impacts of social context, and women's efforts to cope
      outside of medical support services. Nineteen in-depth interviews were conducted
      with women experiencing depression or anxiety-like symptoms in a wider study of
      services in KwaZulu-Natal, South Africa. Thematic analysis was framed by
      Summerfield's emphasis on contexts and resilience. Women highlighted family
      conflicts (particularly abandonment by men), community-level violence, poverty
      and HIV/AIDS as drivers of distress. Whilst HIV/AIDS placed significant burdens
      on women, poverty and relationship difficulties were more central in their
      accounts. Four coping mechanisms were identified. Women drew on indigenous local
      resources in their psychological re-framing of negative situations, and their
      mobilisation of emotional and financial support from inter-personal networks,
      churches and HIV support groups. Less commonly, they sought expert advice from
      traditional healers, medical services or social workers, but access to these was
      limited. Though all tried to supplement government grants with income generation
      efforts, only a minority regarded these as successful. Findings support ongoing
      efforts to bolster strained mental health services with support groups, which
      often offer valuable emotional and practical support. Without parallel poverty
      alleviation strategies, however, support groups may sometimes offer little more
      than encouraging passive acceptance of the inevitability of suffering-
      potentially exacerbating the hopelessness underpinning women's distress.

PMID- 24670518
TI  - Type IV collagen alpha1-chain noncollagenous domain blocks MMP-2 activation both
      in-vitro and in-vivo.
AB  - alpha1(IV)NC1 inhibits angiogenesis by regulating MAPK activation, this
      biological function was partly attributed alpha1(IV)NC1 binding to alpha1beta1
      integrin. However, its potent antiangiogenic activity and the molecular targets
      of alpha1(IV)NC1 has not been investigated. In the present study, the regulation
      of MMP-2 activation by alpha1(IV)NC1 was evaluated. alpha1beta1-integrin which is
      required for inhibition of angiogenesis is not playing a role in cellular
      invasion and inhibition of MMP-2 activation by alpha1(IV)NC1. We found that
      alpha1(IV)NC1 binds the CBD of MMP-2 and forming a stable complex that prevents
      activation of MMP-2. The antiangiogenic activity of alpha1(IV)NC1 is mediated, in
      part, by this binding activity. In addition, up-regulation of TIMP-2 by
      alpha1(IV)NC1 led to saturation of MT1-MMP binding sites, which in turn led to
      inhibition of MMP-2 activation. In-vivo studies using alpha1-integrin null-mice
      treated with higher doses of alpha1(IV)NC1 showed integrin independent inhibition
      of tumor growth and active-MMP-2, without affecting MMP-9, MMP-7 and angiostatin.

PMID- 24670519
TI  - Understanding the development of minimum unit pricing of alcohol in Scotland: a
      qualitative study of the policy process.
AB  - BACKGROUND: Minimum unit pricing of alcohol is a novel public health policy with
      the potential to improve population health and reduce health inequalities.
      Theories of the policy process may help to understand the development of policy
      innovation and in turn identify lessons for future public health research and
      practice. This study aims to explain minimum unit pricing's development by taking
      a 'multiple-lenses' approach to understanding the policy process. In particular,
      we apply three perspectives of the policy process (Kingdon's multiple streams,
      Punctuated-Equilibrium Theory, Multi-Level Governance) to understand how and why
      minimum unit pricing has developed in Scotland and describe implications for
      efforts to develop evidence-informed policymaking. METHODS: Semi-structured
      interviews were conducted with policy actors (politicians, civil servants,
      academics, advocates, industry representatives) involved in the development of
      MUP (n = 36). Interviewees were asked about the policy process and the role of
      evidence in policy development. Data from two other sources (a review of policy
      documents and an analysis of evidence submission documents to the Scottish
      Parliament) were used for triangulation. FINDINGS: The three perspectives provide
      complementary understandings of the policy process. Evidence has played an
      important role in presenting the policy issue of alcohol as a problem requiring
      action. Scotland-specific data and a change in the policy 'image' to a population
      based problem contributed to making alcohol-related harms a priority for action.
      The limited powers of Scottish Government help explain the type of price
      intervention pursued while distinct aspects of the Scottish political climate
      favoured the pursuit of price-based interventions. CONCLUSIONS: Evidence has
      played a crucial but complex role in the development of an innovative policy.
      Utilising different political science theories helps explain different aspects of
      the policy process, with Multi-Level Governance particularly useful for
      highlighting important lessons for the future of public health policy.

PMID- 24670520
TI  - Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from
      ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial
      of HIV-1 RNA-suppressed participants.
AB  - OBJECTIVE: To evaluate the efficacy and safety of antiretroviral simplification
      from a ritonavir-boosted protease inhibitor-based regimen [protease
      inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); >=6
      months of exposure prior to study entry with no prior treatment failure] to the
      single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil
      fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants.
      DESIGN: Phase 3b, randomized, open-label, international, 48-week switch study.
      METHODS: Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately
      or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed
      switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12%
      margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in
      maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot
      analysis. RESULTS: A total of 476 participants were randomized and received at
      least one dose of study drug. Demographics and baseline characteristics were
      similar between arms. The primary objective of noninferiority at week 24 was met:
      HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF
      versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95%
      confidence interval -1.6 to 9.1%). Through week 48, 89.3% of participants in the
      immediate switch group maintained virologic suppression. High rates of
      suppression were maintained with RPV/FTC/TDF regardless of participant's pre
      antiretroviral HIV-1 RNA level. Overall development of resistance mutations after
      switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density
      lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF
      recipients than those in the protease inhibitor+RTV+ two NRTIs group. CONCLUSION:
      Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen
      in virologically suppressed, HIV-1-infected participants maintained virologic
      suppression with a low risk of virologic failure, while improving total
      cholesterol, LDL, and triglycerides.

PMID- 24670521
TI  - Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth: a
      structural equation model analysis.
AB  - OBJECTIVE: To examine the relationship between markers of vascular dysfunction
      and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and
      perinatally HIV-exposed but uninfected (PHEU) youth. DESIGN: Cross-sectional
      design within a prospective, 15-site US-based cohort study. METHODS:
      Neurodevelopmental outcomes were evaluated in relation to nine selected vascular
      biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for
      adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble
      vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte
      chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1),
      and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth
      Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and
      four index scores. Factor analysis was conducted to reduce the biomarkers to
      fewer factors with related biological roles. Structural equation models (SEMs)
      were used to measure associations between resulting factors and WISC-IV scores.
      RESULTS: Mean participant age was 11.4 years, 54% were female, 70% black. The
      nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and
      IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin).
      Adiponectin showed little correlation with any factor. SEMs revealed significant
      negative association of F1 with WISC-IV processing speed score in the total
      cohort. This effect remained significant after adjusting for HIV status and other
      potential confounders. A similar association was observed when restricted to
      PHIV+ participants in both unadjusted and adjusted SEMs. CONCLUSION: Aggregate
      measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated
      with relatively decreased processing speed in both PHIV+ and PHEU youth.

PMID- 24670522
TI  - The cost-effectiveness of improved hepatitis C virus therapies in HIV/hepatitis C
      virus coinfected patients.
AB  - OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of strategies to
      treat hepatitis C virus (HCV) in HIV/HCV coinfected patients in the United
      States. PARTICIPANTS: Simulated cohort of HIV/HCV genotype 1 coinfected,
      noncirrhotic, HCV treatment-naive individuals enrolled in US HIV guideline
      concordant care. DESIGN/INTERVENTIONS: Monte Carlo simulation comparing five
      strategies: no treatment; dual therapy with pegylated-interferon (PEG) and
      ribavirin (RBV); 'PEG/RBV trial' in which all patients initiate dual therapy and
      switch to triple therapy upon failure; 'IL28B triage' in which patients initiate
      either dual therapy or triple therapy based on their IL28B allele type; and
      PEG/RBV and telaprevir (TPV) triple therapy. Sensitivity analyses varied
      efficacies and costs and included a scenario with interferon (IFN)-free therapy.
      MAIN MEASURES: Sustained virologic response (SVR), life expectancy, discounted
      quality-adjusted life expectancy (QALE), lifetime medical costs, and incremental
      cost-effectiveness ratios (ICERs) in $/quality-adjusted life years (QALY) gained.
      RESULTS: 'PEG/RBV trial,' 'IL28B triage,' and 'triple therapy' each provided 72%
      SVR and extended QALE compared with 'dual therapy' by 1.12, 1.14, and 1.15 QALY,
      respectively. The ICER of 'PEG/RBV trial' compared with 'dual therapy' was $37
      500/QALY. 'IL28B triage' and 'triple therapy' provided little benefit compared
      with 'PEG/RBV trial,' and both had ICERs exceeding $300 000/QALY. In sensitivity
      analyses, IFN-free treatment attaining 90% SVR had an ICER less than $100
      000/QALY compared with 'PEG/RBV trial' when its cost was $109 000 or less (125%
      of the cost of PEG/RBV/TVR). CONCLUSION: HCV protease inhibitors are most
      efficiently used in HIV/HCV coinfection after a trial of PEG/RBV, sparing
      protease inhibitors for those who attain rapid virologic response and SVR. The
      cost-effectiveness of IFN-free regimens for HIV/HCV coinfection will depend on
      the cost of these therapies.

PMID- 24670524
TI  - Educational attainment and risk of HIV infection, response to antiretroviral
      treatment, and mortality in HIV-infected patients.
AB  - OBJECTIVE: To estimate association between educational attainment and risk of HIV
      diagnosis, response to HAART, all-cause, and cause-specific mortality in Denmark
      in 1998-2009. DESIGN: Prospective, population-based cohort study including 1277
      incident HIV-infected patients without hepatitis C virus or intravenous drug
      abuse identified in the Danish HIV Cohort Study and 5108 individually matched
      population controls. METHODS: Data on educational attainment, categorized as low,
      medium, or high, were identified in The Danish Attainment Register. Logistic and
      Poisson regression were used to estimate odds ratios (ORs) and mortality rate
      ratios (MRRs). RESULTS: OR of HIV diagnosis was 1.7 (95% confidence interval, CI
      1.3-2.3) among heterosexual individuals with low educational attainments, but no
      associations between educational attainment and time to HAART initiation, CD4
      cell count, or viral suppression were identified. All-cause MRRs were 1.8 (95% CI
      1.0-3.2) and 1.8 (1.1-2.8) for HIV-infected patients and population controls with
      low educational attainment compared with medium and high educational attainment.
      MRRs for smoking and alcohol-related deaths were 3.6 (95% CI 1.5-8.9) for HIV
      infected patients and 2.0 (95% CI 1.2-3.4) for population controls with low
      educational attainment compared with medium and high educational attainment.
      CONCLUSION: With free and equal access to healthcare, low educational attainment
      might increase risk of HIV infection among heterosexual individuals, but was not
      associated with late/very late presentation of HIV, time to HAART initiation, or
      HAART response. However, low educational attainment substantially increased
      lifestyle-related mortality, which indicates that increased mortality in HIV
      infected patients with low educational attainments stems from risk factors
      unrelated to HIV.

PMID- 24670523
TI  - HIV therapy, metabolic and cardiovascular health are associated with glomerular
      hyperfiltration among men with and without HIV infection.
AB  - OBJECTIVE: Diabetes and hypertension, common conditions in antiretroviral-treated
      HIV-infected individuals, are associated with glomerular hyperfiltration, which
      precedes the onset of proteinuria and accelerated kidney function decline. In the
      Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is
      present and associated with metabolic, cardiovascular, HIV and treatment risk
      factors among HIV-infected men. DESIGN: Cross-sectional cohort using direct
      measurement of glomerular filtration rate by iohexol plasma clearance for 367 HIV
      infected men and 241 HIV-uninfected men who were free of chronic kidney disease.
      METHODS: Hyperfiltration was defined as glomerular filtration rate above 140-1
      ml/min per 1.73 m per year over age 40. Multivariate logistic regression was used
      to estimate the odds ratios (ORs) of prevalent hyperfiltration for metabolic,
      cardiovascular, HIV and cumulative antiretroviral exposure factors. RESULTS:
      Among individuals without chronic kidney disease, the prevalence of
      hyperfiltration was higher for HIV-infected participants (25%) compared to
      uninfected participants (17%; P = 0.01). After adjustment, HIV infection remained
      associated with hyperfiltration [OR 1.70, 95% confidence interval (CI) 1.11-2.61]
      and modified the association between diabetes and hyperfiltration, such that the
      association among HIV-uninfected men (OR 2.56, 95% CI 1.33-5.54) was not observed
      among HIV-infected men (OR 1.19, 95% CI 0.69-2.05). These associations were
      independent of known risk factors for hyperfiltration. Indicators of
      hyperglycemia and hypertension were also associated with hyperfiltration as was
      cumulative zidovudine exposure. CONCLUSION: Hyperfiltration, a potential
      modifiable predictor of kidney disease progression, is significantly higher among
      antiretroviral-treated HIV-infected men. Furthermore, HIV-infection nullifies the
      association of diabetes and hyperfiltration present in HIV-uninfected men.

PMID- 24670526
TI  - Better economic tools for evaluating health and development investments.

PMID- 24670525
TI  - Financing structural interventions: going beyond HIV-only value for money
      assessments.
AB  - OBJECTIVE: Structural interventions can reduce HIV vulnerability. However, HIV
      specific budgeting, based on HIV-specific outcomes alone, could lead to the
      undervaluation of investments in such interventions and suboptimal resource
      allocation. We investigate this hypothesis by examining the consequences of
      alternative financing approaches. METHODS: We compare three approaches for
      deciding whether to finance a structural intervention to keep adolescent girls in
      school in Malawi. In the first, HIV and non-HIV budget holders participate in a
      cross-sectoral cost-benefit analysis and fund the intervention if the benefits
      outweigh the costs. In the second silo approach, each budget holder considers the
      cost-effectiveness of the intervention in terms of their own objectives and funds
      the intervention on the basis of their sector-specific thresholds of what is cost
      effective or not. In the third cofinancing approach, budget holders use cost
      effectiveness analysis to determine how much they would be willing to contribute
      towards the intervention, provided that other sectors are willing to pay for the
      remaining costs. In addition, we explore approaches for determining the HIV share
      in the cofinancing scenario. RESULTS: We find that efficient structural
      interventions may be less likely to be prioritized, financed and taken to scale
      where sectors evaluate their options in isolation. A cofinancing approach
      minimizes welfare loss and could be incorporated in a sector budgeting
      perspective. CONCLUSION: Structural interventions may be underimplemented and
      their cross-sectoral benefits foregone. Cofinancing provides an opportunity for
      multiple HIV, health and development objectives to be achieved simultaneously,
      but will require effective cross-sectoral coordination mechanisms for planning,
      implementation and financing.

PMID- 24670527
TI  - Occurrence of etravirine/rilpivirine-specific resistance mutations selected by
      efavirenz and nevirapine in Kenyan patients with non-B HIV-1 subtypes failing
      antiretroviral therapy.
AB  - Resistance to efavirenz and nevirapine has not been associated with mutations at
      position 138 of reverse transcriptase. In an evaluation of virologic suppression
      rates in PEPFAR (President's Emergency Plan For AIDS Relief) clinics in Kenya
      among patients on first-line therapy (RV288), 63% (617/975) of randomly selected
      patients on antiretroviral therapy were suppressed (HIV RNA<400 copies/ml). Among
      those with non-nucleoside reverse transcriptase inhibitor resistance (n = 101),
      14 (13.8%) had substitutions at 138 (A, G, K or Q), mutations selected only by
      etravirine and rilpivirine in subtype B viruses. All 14 patients received
      efavirenz or nevirapine, not etravirine or rilpivirine, and were predominantly
      subtype A1. This may be the first report of efavirenz and nevirapine selecting
      these mutations in these subtypes.

PMID- 24670528
TI  - Azathioprine can be safely used in HIV-infected individuals.

PMID- 24670529
TI  - Mandibular osteonecrosis and dental exfoliation after trigeminal zoster in an HIV
      infected patient: case report and review of the literature.

PMID- 24670530
TI  - Reversible bone lesions induced by tenofovir disoproxil fumarate.

PMID- 24670531
TI  - Specific retrograde transduction of spinal motor neurons using lentiviral vectors
      targeted to presynaptic NMJ receptors.
AB  - To understand how receptors are involved in neuronal trafficking and to be able
      to utilize them for specific targeting via the peripheral route would be of great
      benefit. Here, we describe the generation of novel lentiviral vectors with
      tropism to motor neurons that were made by coexpressing onto the lentiviral
      surface a fusogenic glycoprotein (mutated sindbis G) and an antibody against a
      cell-surface receptor (Thy1.1, p75(NTR), or coxsackievirus and adenovirus
      receptor) on the presynaptic terminal of the neuromuscular junction. These
      vectors exhibit binding specificity and efficient transduction of receptor
      positive cell lines and primary motor neurons in vitro. Targeting of each of
      these receptors conferred to these vectors the capability of being transported
      retrogradely from the axonal tip, leading to transduction of motor neurons in
      vitro in compartmented microfluidic cultures. In vivo delivery of coxsackievirus
      and adenovirus receptor-targeted vectors in leg muscles of mice resulted in
      predicted patterns of motor neuron labeling in lumbar spinal cord. This opens up
      the clinical potential of these vectors for minimally invasive administration of
      central nervous system-targeted therapeutics in motor neuron diseases. 

PMID- 24670532
TI  - Nature's lab for derivatization: new and revised structures of a variety of
      streptophenazines produced by a sponge-derived Streptomyces strain.
AB  - Eight streptophenazines (A-H) have been identified so far as products of
      Streptomyces strain HB202, which was isolated from the sponge Halichondria
      panicea from the Baltic Sea. The variation of bioactivities based on small
      structural changes initiated further studies on new derivatives. Three new
      streptophenazines (I-K) were identified after fermentation in the present study.
      In addition, revised molecular structures of streptophenazines C, D, F and H are
      proposed. Streptophenazines G and K exhibited moderate antibacterial activity
      against the facultative pathogenic bacterium Staphylococcus epidermidis and
      against Bacillus subtilis. All tested compounds (streptophenazines G, I-K) also
      showed moderate activities against PDE 4B. 

PMID- 24670533
TI  - Synthesis and evaluation of some new aza-B-homocholestane derivatives as
      anticancer agents.
AB  - Using analogues of some marine steroidal oximes as precursors, a series of aza-B
      homocholestane derivatives possessing different substituted groups at the 3
      position of the steroidal nucleus were synthesized. Their biological activity
      against cancer cell proliferation was determined with multiple cancer cell lines.
      Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3
      thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via
      apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better
      potency to inhibit cancer cell proliferation. In addition, compound 15 was
      further evaluated with three dimensional (3D) multicellular spheroids assay to
      determine its potency against spheroid growth. The structure-activity
      relationship (SAR) generated in the studies is valuable for the design of novel
      chemotherapeutic agents. 

PMID- 24670534
TI  - High resolution copy number variation data in the NCI-60 cancer cell lines from
      whole genome microarrays accessible through CellMiner.
AB  - Array-based comparative genomic hybridization (aCGH) is a powerful technique for
      detecting gene copy number variation. It is generally considered to be robust and
      convenient since it measures DNA rather than RNA. In the current study, we
      combine copy number estimates from four different platforms (Agilent 44 K,
      NimbleGen 385 K, Affymetrix 500 K and Illumina Human1Mv1_C) to compute a
      reliable, high-resolution, easy to understand output for the measure of copy
      number changes in the 60 cancer cells of the NCI-DTP (the NCI-60). We then relate
      the results to gene expression. We explain how to access that database using our
      CellMiner web-tool and provide an example of the ease of comparison with
      transcript expression, whole exome sequencing, microRNA expression and response
      to 20,000 drugs and other chemical compounds. We then demonstrate how the data
      can be analyzed integratively with transcript expression data for the whole
      genome (26,065 genes). Comparison of copy number and expression levels shows an
      overall medium high correlation (median r = 0.247), with significantly higher
      correlations (median r = 0.408) for the known tumor suppressor genes. That
      observation is consistent with the hypothesis that gene loss is an important
      mechanism for tumor suppressor inactivation. An integrated analysis of concurrent
      DNA copy number and gene expression change is presented. Limiting attention to
      focal DNA gains or losses, we identify and reveal novel candidate tumor
      suppressors with matching alterations in transcript level. 

PMID- 24670535
TI  - mGluR5 promotes the differentiation of rat neural progenitor cells into
      cholinergic neurons and activation of extracellular signal-related protein
      kinases.
AB  - Metabotropic glutamate receptors (mGluRs) regulate neurogenesis in the mammalian
      central nervous system during development and throughout adulthood. However, the
      mechanisms remain unknown. The present study was aimed at investigating the
      effect of mGluR5 on the differentiation of rat neural progenitor cells (NPCs)
      into neurons as well as the underlying molecular mechanisms. NPCs were treated
      with mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), mGluR5 siRNA,
      and antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride (MPEP),
      respectively. Three different subtypes of neurons (cholinergic, GABAergic, and
      dopaminergic neurons) were evaluated, and the activation of signaling pathways of
      mitogen-activated protein kinases was determined. Results showed that CHPG caused
      rat NPCs to differentiate into neurons, whereas mGluR5 siRNA and MPEP inhibited
      the cell differentiation. The proportion of cholinergic neurons increased with
      CHPG treatment and decreased after siRNA or MPEP treatment, whereas there were no
      significant changes in the proportions of GABAergic and dopaminergic neurons
      after treatment. The phosphorylated ERK1/2 levels increased after CHPG treatment
      and decreased after siRNA or MPEP treatment. In conclusion, our findings showed
      that mGluR5 caused rat NPCs to differentiate into cholinergic neurons by
      activating ERKs, suggesting that mGluR5 may play a significant role in the
      mechanism and treatment of degenerative diseases such as Alzheimer's disease. 

PMID- 24670536
TI  - A disintegrin and metalloprotease (ADAM)10 is highly expressed in hepatocellular
      carcinoma and is associated with tumour progression.
AB  - OBJECTIVE: A disintegrin and metalloprotease (ADAM)10 has been implicated in the
      progression of various solid tumours. Little is known, however, about its role in
      hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the
      protein and transcript level expression of ADAM10 in HCC patients. METHODS:
      Samples of HCC and adjacent noncancerous liver tissue were taken during liver
      resection surgery. Immunostaining was used to measure ADAM10 protein expression
      levels and quantitative reverse- transcription polymerase chain reaction was used
      to measure ADAM10 mRNA expression levels. Levels of ADAM10 were compared, and a
      survival analysis undertaken. RESULTS: In total, 98 HCC patient samples were
      studied. There were significant associations between protein levels of ADAM10 and
      tumour grade, amount of tumour differentiation, tumour size and the presence of
      metastasis. Furthermore, ADAM10 protein expression was significantly associated
      with shortened patient survival. CONCLUSIONS: ADAM10 is strongly expressed in a
      large proportion of HCC cases, which is in agreement with findings in other
      tumour entities. Expression of ADAM10 may serve as a useful molecular marker for
      HCC.

PMID- 24670537
TI  - Utilization of rapid infusion system with cold saline in the induction of
      therapeutic hypothermia.
AB  - OBJECTIVE: To examine the cooling effectiveness of a rapid infusion system (RIS)
      during induction of therapeutic hypothermia. METHODS: This laboratory study
      simulated the effect of three fluid delivery methods: rapid dripping without any
      other equipment (control); RIS; pressure bag. Cold energy loss (C * min) was
      calculated as: (temperature of the proximal thermoprobe--temperature of the
      distal thermoprobe) * (total infusion time). RESULTS: Infusion time was
      significantly shorter and cold energy loss significantly lower in the RIS group
      than in the two other groups. CONCLUSIONS: RIS preserves the cold energy of fluid
      more effectively than pressure bag or control. RIS allows for rapid infusion at a
      constant pressure and can be easily applied in an emergency setting.

PMID- 24670538
TI  - Immunohistochemical levels of cyclo-oxygenase-2, matrix metalloproteinase-9 and
      vascular endothelial growth factor in papillary thyroid carcinoma and their
      clinicopathological correlations.
AB  - OBJECTIVE: To measure the levels of cyclo-oxygenase (COX)-2, matrix
      metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF)
      immunostaining in papillary thyroid carcinoma (PTC) and benign thyroid tumours,
      and to investigate potential correlations between their levels and
      clinicopathological characteristics. METHODS: The levels of immunohistochemical
      staining of COX-2, MMP-9 and VEGF proteins were measured in tumours from patients
      with PTC and compared with specimens from patients with benign thyroid tumours.
      The association between the levels of COX-2, MMP-9 and VEGF proteins and
      clinicopathological characteristics in patients with PTC was also analysed.
      RESULTS: A total of 66 patients with PTC and 40 patients with benign thyroid
      tumours participated in the study. The rates of positive immunostaining for COX
      2, MMP-9 and VEGF in PTC tumours were significantly higher than those in benign
      thyroid tumours. There were significant positive associations between positive
      immunostaining for COX-2, MMP-9 and VEGF proteins and age (>=45 years), clinical
      stage (III-IV) and tumour diameter (>= 2 cm). CONCLUSION: Combined
      immunohistochemical evaluation of the levels of COX-2, MMP-9 and VEGF in PTC
      might be a useful marker for the diagnosis of PTC.

PMID- 24670539
TI  - [Let it happen - help it happen - make it happen].

PMID- 24670540
TI  - [Aspects of quality of life of residents of a nursing oasis from the perspectives
      of relatives and nurses- qualitative results of an evaluation study].
AB  - A nursing oasis (NO) can be understood as a version of special care units. The
      focus is on a constantly living arrangement for people with severe dementia in
      nursing homes (multiple person room). Nurses are permanently present during the
      day shift. The question has to be raised which characteristics of quality of life
      (QoL) are mentioned and how nurses and relatives do assess this concept.
      Qualitative Results of a two-year evaluation study of 15 people living in NOs are
      presented. Data were collected during four (five) group discussions with 8 nurses
      (15 relatives). Additionally problem-based interviews were realized. Data
      evaluation was oriented to the grounded theory. The findings show that primarily
      the focus of QoL in NOs was on psychophysical well-being. Assessments of
      relatives and nurses were prevailing positive and could be interpreted in the
      light of the Festingers' social-psychological "Theory of Cognitive Dissonance".
      Comparisons between the situation before and after the implementation of the NOs
      were shown to be relevant for the overall assessments. All in all we have to deal
      with the construction of "care worlds of everyday life" in long term care
      institutions. 

PMID- 24670541
TI  - [What women want: a qualitative study about postnatal midwifery care at home].
AB  - In Switzerland, decreases in regular hospital treatment after birth are leading
      increasingly to mother and child being cared for at home by independent midwives.
      The research herein was carried out in order to understand the needs of mothers
      in their home once they leave the hospital and what this midwife provided care
      consists of. In 2008, eight women from central Switzerland were interviewed on
      two separate occasions after the birth of their child, and the interviews were
      analysed using content analysing techniques. Mothers explained that they wanted
      their baby and themselves to be well cared for. They needed rest and support for
      recuperation and wished to spend quality time with their new family. The midwifes
      assisted the mothers to fulfil their needs by counselling, by instructing and by
      giving information, but they rarely encouraged them to be together as a family.
      The relationship between midwife and mother turned out to be an important
      support. Mothers were satisfied if mutual trust was built and if the midwife
      perceived their needs, respected their autonomy and took the time to be with
      them. Midwives contribute to the basic well-being of families and support women
      with medical expertise and ongoing care. Furthermore families need support in
      general household issues so that new mothers can recover sufficiently.

PMID- 24670542
TI  - [Experiences of relatives, who witnessed resuscitation or invasive procedures in
      life-threatening situations at the bedside of the next of kin or attending in a
      waiting room].
AB  - Worldwide the majority of relatives endorsed family witnessed resuscitation and
      witnessed invasive procedures (FWR) and considered this practice as helpful.
      However, professionals are primarily against this practice. How relatives in
      Swiss hospitals experience these difficult situations is unknown. The aim of this
      qualitative study is to describe and understand the experiences of relatives who
      witnessed resuscitation in a Swiss hospital at the bedside of her next of kin or
      attending in a waiting room. Interviews were conducted with ten relatives between
      September 2011 and June 2012 and analyzed with the method of interpretive
      phenomenology. Four themes derived from the data: "be present", "want to be
      informed", "have confidence" and "looking for support". Attending relatives gave
      to protocol that FWR allowed them to assist their next of kin. Relatives, who
      were waiting outside, felt uncertainty and fear. Relatives wanted FWR and other
      relatives didn't want FWR. Relatives experienced a rapid flow of clear
      information, but also vague, insufficient or delayed messages. They spoke of
      great faith, as well as of ambivalence and mistrust in medical and nursing skills
      of professionals. Relatives reported to cope with the difficult situation: by
      providing support within the family, pray with the family and professional
      support. It is therefore recommended to offer relatives FWR and to develop
      guidelines that direct the support of relatives. 

PMID- 24670543
TI  - [Variability in nursing workload within Swiss Diagnosis Related Groups].
AB  - Nursing care inputs represent one of the major cost components in the Swiss
      Diagnosis Related Group (DRG) structure. High and low nursing workloads in
      individual cases are supposed to balance out via the DRG group. Research results
      indicating possible problems in this area cannot be reliably extrapolated to
      SwissDRG. An analysis of nursing workload figures with DRG indicators was carried
      out in order to decide whether there is a need to develop SwissDRG classification
      criteria that are specific to nursing care. The case groups were determined with
      SwissDRG 0.1, and nursing workload with LEP Nursing 2. Robust statistical methods
      were used. The evaluation of classification accuracy was carried out with R2 as
      the measurement of variance reduction and the coefficient of homogeneity (CH). To
      ensure reliable conclusions, statistical tests with bootstrapping methods were
      performed. The sample included 213 groups with a total of 73930 cases from ten
      hospitals. The DRG classification was seen to have limited explanatory power for
      variability in nursing workload inputs, both for all cases (R2 = 0.16) and for
      inliers (R2 = 0.32). Nursing workload homogeneity was statistically significant
      unsatisfactory (CH < 0.67) in 123 groups, including 24 groups in which it was
      significant defective (CH < 0.60). Therefore, there is a high risk of high and
      low nursing workloads not balancing out in these groups, and, as a result, of
      financial resources being wrongly allocated. The development of nursing-care
      specific SwissDRG classification criteria for improved homogeneity and variance
      reduction is therefore indicated. 

PMID- 24670544
TI  - ["And suddenly I have a tumor" - the situation of family S./N].
AB  - BACKGROUND: Many families affected by a terminal illness need professional help
      and support. In order to be able to cope with emotional stress, loss of light
      heartedness and changes in family structure thorough information is important for
      patients and their families. The Calgary Family-Assessment and Calgary Family
      Intervention-Model are suitable to determine the needs of concerned families and
      hence to offer appropriate interventions. PURPOSE: In an instrumental case study
      the situation of Mrs. S.2 and her family was analyzed. Mrs. S. is suffering from
      an inoperable adenocarcinoma. METHOD: An assessment classified the different
      information given during the first meeting and determined the focus of the
      interventions. RESULTS: Interventions concentrated on cognitive and emotional
      support. CONCLUSIONS: The case study showed how family models for nurses could
      systematically guide professionals in supporting families. Listening and spending
      time with the concerned person and their families showed to offer important
      factors, which were perceived as very helpful by the families.

PMID- 24670545
TI  - [Risk adjustment in quality comparison - why hierarchical models?].

PMID- 24670546
TI  - [Long-term outcomes of stroke rehabilitation: patients and informal caregivers].

PMID- 24670553
TI  - The associations between serum brain-derived neurotrophic factor, potential
      confounders, and cognitive decline: a longitudinal study.
AB  - Brain-derived neurotrophic factor (BDNF) plays a role in the maintenance and
      function of neurons. Although persons with Alzheimer's disease have lower
      cortical levels of BDNF, evidence regarding the association between circulating
      BDNF and cognitive function is conflicting. We sought to determine the correlates
      of BDNF level and whether BDNF level was prospectively associated with cognitive
      decline in healthy older adults. We measured serum BDNF near baseline in 912
      individuals. Cognitive status was assessed repeatedly with the modified Mini
      Mental Status Examination and the Digit Symbol Substitution test over the next 10
      years. We evaluated the association between BDNF and cognitive decline with
      longitudinal models. We also assessed the association between BDNF level and
      demographics, comorbidities and health behaviors. We found an association between
      serum BDNF and several characteristics that are also associated with dementia
      (race and depression), suggesting that future studies should control for these
      potential confounders. We did not find evidence of a longitudinal association
      between serum BDNF and subsequent cognitive test trajectories in older adults,
      although we did identify a potential trend toward a cross-sectional association.
      Our results suggest that serum BDNF may have limited utility as a biomarker of
      prospective cognitive decline. 

PMID- 24670554
TI  - Identifying the key elements of an education package to up-skill
      multidisciplinary adult specialist palliative care teams caring for young adults
      with life-limiting conditions: an online Delphi study.
AB  - OBJECTIVES: To collect the views of experts to inform the development of an
      education package for multidisciplinary adult specialist palliative care (SPC)
      teams caring for young people with life-limiting conditions. METHODS: A modified
      online Delphi process collated expert opinion on format, delivery and content of
      an education package to up-skill adult SPC teams. Round 1 participants (n=44)
      answered free-text questions, generating items for Round 2. In Round 2, 68
      participants rated the extent to which they agreed/disagreed with the items on 5
      point Likert-type scales. Median and mean scores assessed the importance of each
      item. IQR scores assessed level of consensus for each item; items lacking
      consensus were rerated by 35 participants in Round 3. RESULTS: In the Delphi,
      consensus was reached on a range of suggested formats, on who should deliver the
      training, and on several clinical, psychosocial and practical topics.
      CONCLUSIONS: Development of a continuous/rolling programme of education, tailored
      for content and mode of delivery and incorporated into working practice is
      recommended. As a direct outcome of the results of this study, a series of six
      linked study days has been established, focusing specifically on the issues
      around caring for young adults with life-limiting conditions and palliative care
      needs.

PMID- 24670555
TI  - Evidence of a dominance hierarchy in captive Caribbean flamingos and its relation
      to pair bonding and physiological measures of health.
AB  - Caribbean flamingo social structure, how pair bonds affect the structure of the
      flock, and how social stress affects health measured by heterophil to lymphocyte
      ratios (H/L) were investigated at the Philadelphia Zoo. It was hypothesized that
      a hierarchy may become apparent by analyzing agonistic interactions and that
      paired individuals would share similar places within the hierarchy. Furthermore,
      it was hypothesized that a negative relationship between H/L ratio and dominance
      would exist. Forty observations were conducted and in 70% of interactions
      instigating bird(s) won the encounter, suggesting either some advantage for
      instigating birds or a prior expectation of an encounter's outcome based upon an
      understanding of the flock's hierarchy. The flock possessed a semi-linear
      hierarchy (in terms of wins/losses) and birds with higher pair-bond strengths
      maintained dominant positions, suggesting that pair-bonding may help individuals
      become more successful in agonistic encounters. Birds who won more often had
      higher lymphocytes percentages and analyses suggested a trend indicating dominant
      birds may be less stressed. A semi-linear hierarchy was also found in terms of
      initiation/being targeted, and a bird's rank on the dominance (wins/losses) and
      initiate/target hierarchies were positively correlated, suggesting that
      subdominant birds were targeted by dominant birds more frequently than vice
      versa. 

PMID- 24670556
TI  - Updating the international standards for tuberculosis care.

PMID- 24670557
TI  - The importance of measuring asthma control in emerging economies.

PMID- 24670558
TI  - Delays in diagnosis and treatment of pulmonary tuberculosis in India: a
      systematic review.
AB  - OBJECTIVE: To systematically review Indian literature on delays in tuberculosis
      (TB) diagnosis and treatment. METHODS: We searched multiple sources for studies
      on delays in patients with pulmonary TB and those with chest symptoms. Studies
      were included if numeric data on any delay were reported. Patient delay was
      defined as the interval between onset of symptoms and the patient's first contact
      with a health care provider. Diagnostic delay was defined as the interval between
      the first consultation with a health care provider and diagnosis. Treatment delay
      was defined as the interval between diagnosis and initiation of anti-tuberculosis
      treatment. Total delay was defined as time interval from the onset of symptoms
      until treatment initiation. RESULTS: Among 541 potential citations identified, 23
      studies met the inclusion criteria. Included studies used a variety of
      definitions for onset of symptoms and delays. Median estimates of patient,
      diagnostic and treatment delay were respectively 18.4 (IQR 14.3-27.0), 31.0 (IQR
      24.5-35.4) and 2.5 days (IQR 1.9-3.6) for patients with TB and those with chest
      symptoms combined. The median total delay was 55.3 days (IQR 46.5-61.5). About
      48% of all patients first consulted private providers; an average of 2.7 health
      care providers were consulted before diagnosis. Number and type of provider first
      consulted were the most important risk factors for delay. CONCLUSIONS: These
      findings underscore the need to develop novel strategies for reducing patient and
      diagnostic delays and engaging first-contact health care providers.

PMID- 24670559
TI  - Impact of diabetes on diagnostic delay for pulmonary tuberculosis in Beijing.
AB  - SETTING: Delays in the diagnosis of pulmonary tuberculosis (PTB) increase the
      risk of transmission and severity of the disease. Little information is available
      on PTB patients with diabetes mellitus (DM). OBJECTIVES: To examine the impact of
      DM on delays in diagnosing PTB and the effect of diagnostic delay on the clinical
      presentation of PTB among patients in Beijing, China. DESIGN: In a cross
      sectional study conducted in two PTB dispensaries of Beijing, all confirmed PTB
      patients were screened for DM. Data relating to diagnostic delay and clinical
      presentation of PTB were collected and analysed. RESULTS: Of 1126 PTB patients
      selected, 182 (16.2%) were identified as having DM. The median delay for PTB
      patients with DM (25 days) was significantly higher than that of PTB patients
      without DM (6 days). In a subgroup analysis, diagnostic delay was associated with
      smear positivity among PTB patients with DM (OR 3.10, 95%CI 1.66-5.76) and
      associated with smear positivity (OR 4.38, 95%CI 3.19-6.04), pulmonary cavities
      (OR 2.62, 95%CI 1.85-3.71) and more symptoms (OR 1.81, 95%CI 1.20-2.73) among PTB
      patients without DM. CONCLUSIONS: DM was associated with longer diagnostic
      delays, which in turn was associated with more serious clinical presentations of
      PTB. It is thus necessary to examine risk factors associated with diagnostic
      delay among PTB patients with and without DM.

PMID- 24670560
TI  - Pulmonary tuberculosis in migratory nomadic populations: the missing link in
      Iran's National Tuberculosis Programme.
AB  - OBJECTIVE: To detect pulmonary tuberculosis (PTB) in migratory nomadic
      populations in Fars Province, southern Iran. DESIGN: Cross-sectional study.
      RESULTS: In this study, 5506 (82.8%) of a total nomad population of 6650 from
      1337 tents were screened for PTB. The mean age was 27.4 +/- 18.2 years (range 1
      109). Based on clinical symptoms, 141/5506 (2.6%) were identified as TB suspects.
      One male and three female adult new smear-positive PTB cases were detected,
      giving an incidence rate of 0.7/1000 population compared to 0.08/1000 in the
      general population of the region, and 28.4/1000 TB suspects. The median time to
      onset of symptoms in detected cases was 82.5 days. Tribal stigma against female
      TB patients was one of the main barriers to appropriate health-seeking behaviour.
      CONCLUSIONS: The incidence of smear-positive PTB among migratory nomads is
      approximately nine-fold higher than in the general population. Active screening
      of TB in migratory nomads should be integrated into Iran's national TB control
      programme. The issue of destigmatisation, particularly among female TB patients,
      should also be addressed.

PMID- 24670562
TI  - Tuberculosis remains a challenge despite economic growth in Panama.
AB  - Tuberculosis (TB) is a disease associated with inequality, and wise investment of
      economic resources is considered critical to its control. Panama has recently
      secured its status as an upper-middle-income country with robust economic growth.
      However, the prioritisation of resources for TB control remains a major
      challenge. In this article, we highlight areas that urgently require action to
      effectively reduce TB burden to minimal levels. Our conclusions suggest the need
      for fund allocation and a multidisciplinary approach to ensure prompt laboratory
      diagnosis, treatment assurance and workforce reinforcement, complemented by
      applied and operational research, development and innovation. 

PMID- 24670561
TI  - Can tuberculosis case finding among health-care seeking adults be improved?
      Observations from Bissau.
AB  - SETTING: The Bandim Health Project study area in Bissau, Guinea-Bissau.
      OBJECTIVE: To assess the potential usefulness of predictors (elsewhere applied)
      and clinical scores (TBscore and TBscore II) based on signs and symptoms typical
      of tuberculosis (TB) in case finding. DESIGN: Observational prospective cohort
      study of patients with signs and symptoms suggestive of pulmonary TB (PTB) from
      2010 to 2012. RESULTS: We included 1089 PTB suspects with a mean age of 34 years
      (95%CI 33-35); human immunodeficiency virus (HIV) prevalence was 15.1%. PTB was
      diagnosed in 107 suspects (76.4% sputum smear-positive, 25.2% HIV-infected).
      Cough > 2 weeks had the highest diagnostic ability (area under the receiver
      operating characteristic curve [AUC] 0.66, 95%CI 0.62-0.71), while TBscore < 3
      best excluded PTB (negative likelihood ratio [LR-] 0.3) when HIV status was not
      known. TBscore II >= 3 had the highest diagnostic ability in HIV-infected PTB
      suspects (AUC 0.62, 95%CI 0.53-0.72), while the absence of self-reported weight
      loss best excluded PTB (LR- 0.2). Cough > 2 weeks as a trigger for smear
      microscopy missed 32.1% of smear-positive PTB cases. CONCLUSION: Case finding
      could be improved by screening symptomatic adults for cough and/or weight loss
      using TBscore II as the trigger for smear microscopy. To suspect PTB only in
      patients with cough > 2 weeks (non-HIV-infected) or with current cough, fever,
      weight loss or night sweats (HIV-infected) was not effective in patients whose
      HIV status was unknown at first visit.

PMID- 24670563
TI  - Characterizing tuberculosis genotype clusters along the United States-Mexico
      border.
AB  - We examined the growth of tuberculosis (TB) genotype clusters during 2005-2010 in
      the United States, categorized by country of origin and ethnicity of the index
      case and geographic proximity to the US-Mexico border at the time of TB
      diagnosis. Nationwide, 38.9% of cases subsequent to Mexico-born index cases were
      US-born. Among clusters following US-born Hispanic and US-born non-Hispanic index
      cases, respectively 29.2% and 5.3% of subsequent cluster members were Mexico
      born. In border areas, the majority of subsequent cases were Mexico-born
      following US-born Hispanic (56.4%) and US-born non-Hispanic (55.6%) index cases.
      These findings suggest that TB transmission commonly occurs between US-born and
      Mexico-born persons. Along the US-Mexico border, prioritizing TB genotype
      clusters following US-born index cases for investigation may prevent subsequent
      cases among both US-born and Mexico-born persons. 

PMID- 24670564
TI  - Spatial analysis of tuberculosis in Douala, Cameroon: clustering and links with
      socio-economic status.
AB  - SETTING: Douala, the economic capital of Cameroon, with a network of 20
      diagnostic and treatment centres for tuberculosis (TB). OBJECTIVE: To describe
      the spatial distribution of smear-positive pulmonary tuberculosis (PTB) cases in
      Douala, Cameroon, and to evaluate links between PTB incidence and patients' socio
      economic status (SES). DESIGN: Between May 2011 and April 2012, demographic
      clinical characteristics and global positioning system coordinates for the
      residence of each consenting PTB case were collected. Spatial scan statistic was
      used to identify spatial clusters of tuberculosis. SES data were collected by
      interview during home visits. PTB patients' SES data were compared with those
      available for the whole urban population from a recent demographic and health
      survey. The correlation between PTB incidence and the mean SES of the PTB
      patients was examined by health area (HA). RESULTS: In total, 2132 (84%)
      diagnosed PTB cases were identified and interviewed. Three statistically
      significant spatial clusters were identified. High PTB incidence was
      predominantly found in HAs characterised by low SES. CONCLUSION: There is
      evidence of clustering of PTB cases in Douala. Clusters are mainly found in
      neighbourhoods of low SES. Systematic use of cluster detection techniques for
      regular TB surveillance in Cameroon might aid in the effective deployment of
      National TB Programme resources.

PMID- 24670565
TI  - Molecular epidemiology of Mycobacterium tuberculosis strains circulating in the
      penitentiary system of Kazakhstan.
AB  - A total of 60 Mycobacterium tuberculosis isolates collected from patients in
      prisons in Kazakhstan and 125 from the civilian sector were examined using
      mycobacterial interspersed repetitive units-variable number of tandem repeat
      analysis in 2012. The proportion of tuberculosis strains with unique genotypes
      isolated from the civilian patients was 50.4%, while that in the prison patients
      was 31.7%. This difference was statistically significant (chi(2) 4.42, P 0.035),
      and may reflect a low genetic diversity of M. tuberculosis strains isolated from
      prison patients. The frequencies of mutations in the rpoB531 and katG315 genes of
      the M. tuberculosis strains isolated from the civilians and in the penitentiary
      system were not significantly different (rpoB531: 82.4% vs. 88.3%, and katG315:
      98.4% vs. 100%, respectively). 

PMID- 24670566
TI  - Development of a new ligation-mediated PCR method for the differentiation of
      Mycobacterium tuberculosis strains.
AB  - BACKGROUND: There is a need for rapid, inexpensive methods for analysing a
      limited number of Mycobacterium tuberculosis strains. The ligation-mediated
      polymerase chain reaction (LM-PCR) method appears to be sufficiently
      discriminative and reproducible to be considered as a molecular tool for the
      initial evaluation of hospital outbreaks, laboratory cross-contamination, and
      family or small community transmission. OBJECTIVE: To develop a new LM-PCR method
      based on PCR amplification of the 5'-flanking region of insertion sequence (IS)
      6110 consisting of SalI/PvuII digestion of chromosomal DNA, ligation of a SalI
      linker and differentiation of IS6110-carrying restriction fragments by
      suppression subtractive hybridisation. DESIGN: The fast ligation amplification
      polymorphism (FLAP) method was applied in the analysis of 62 M. tuberculosis
      clinical isolates and compared with IS6110-restriction fragment length
      polymorphism (RFLP) and mycobacterial interspersed repetitive units-variable
      number of tandem repeat (MIRU-VNTR) analyses of the same strains. RESULTS: The
      sensitivity of FLAP was estimated at 0.25 ng/l. FLAP yielded 32 patterns among
      the 62 M. tuberculosis strains compared to respectively 28 and 36 patterns
      obtained using MIRU-VNTR and IS6110-RFLP. Its Hunter-Gaston discriminatory index
      value (0.973) is similar to that of MIRU-VNTR (0.966) and IS6110-RFLP (0.971).
      The specificity of the FLAP patterns was also confirmed. CONCLUSION: FLAP proved
      highly discriminating, sensitive and specific and could be a valuable molecular
      tool, especially for analysing a limited number of M. tuberculosis strains.

PMID- 24670567
TI  - Spot or early morning sample for mycobacterial culture: which?
AB  - Drug resistance studies ideally require two sputum specimens, one spot and one
      early morning, for culture in Lowenstein-Jensen medium. Although the type of
      specimen plays a major role in the detection of acid-fast bacilli using
      microscopy, this type of specimen collection puts unnecessary pressure on
      patients. Two sputum samples, one on the spot and another in the early morning,
      collected from 179 TB patients in cetylpyridinium chloride and processed for
      culture, yielded respectively 89.9% and 87.7% culture positivity, while culture
      positivity increased to 93.3% when both specimens were tested. 

PMID- 24670568
TI  - Isoniazid preventive therapy use among patients on antiretroviral therapy: a
      missed opportunity.
AB  - Isoniazid preventive therapy (IPT) with antiretroviral therapy (ART) reduces
      incident tuberculosis among patients infected with the human immunodeficiency
      virus. We describe IPT use among patients on ART at two primary care clinics in
      South Africa. Of 597 participants interviewed, 100 (16.8%) reported IPT use;
      73.4% (365/497) with no reported IPT use were eligible for IPT. IPT use was
      associated with age <35 years (aOR 1.90, 95%CI 1.18-3.06), and receiving care at
      one clinic as opposed to the other (aOR 4.72, 95%CI 2.69-7.93). The high
      proportion of patients on ART eligible for IPT represents a missed opportunity
      for IPT scale-up. 

PMID- 24670569
TI  - The influence of integrated tuberculosis and human immunodeficiency virus service
      delivery on patient outcomes.
AB  - SETTING: Public health clinics in Cape Town, South Africa. OBJECTIVE: To examine
      the influence of integrated tuberculosis (TB) and human immunodeficiency virus
      (HIV) service delivery on mortality, TB cure and successful treatment completion
      and loss to follow-up of TB-HIV co-infected patients on concurrent anti
      tuberculosis and antiretroviral treatment (ART). DESIGN: A survey instrument was
      used to measure the degree to which TB and HIV services were jointly delivered,
      and patient data were collected retrospectively from clinic sites and the
      Department of Health. Six domains measuring integrated TB and HIV service
      delivery were modelled to assess their relationship with patient outcomes.
      RESULTS: Two domains, integrated TB and ART service delivery and the delivery of
      TB and HIV care by one clinical team, were associated with lowered odds of death.
      Care by the same clinical team was also associated with reduced loss to follow
      up. CONCLUSION: Overall, these findings show that the organization and delivery
      of health services are important factors that influence health outcomes. These
      findings strongly support efforts by local governments to integrate TB and ART
      services, and may help to alleviate concerns that restructuring of TB programs
      could have a negative impact on long-standing gains.

PMID- 24670570
TI  - Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy:
      a pilot study.
AB  - SETTING: Tuberculosis (TB) is a common cause of mortality and morbidity in
      children infected with the human immunodeficiency virus (HIV). Data on isoniazid
      preventive therapy (IPT) efficacy in HIV-infected children receiving
      antiretroviral therapy (ART) are inconclusive. OBJECTIVE: To assess the efficacy,
      tolerability and safety of isoniazid (INH) in HIV-infected children on ART.
      DESIGN: A pilot randomised controlled study of INH was undertaken in HIV-infected
      children on ART. The primary outcome measure was TB disease or death. RESULTS: A
      total of 167 children were randomised to receive INH (n = 85) or placebo (n =
      82), and followed for a median of 34 months (interquartile range [IQR] 24-52).
      The median age was 35 months (IQR 15-65). There was one death in a child on INH
      and none in the placebo group. Eleven (6.6%) cases of TB occurred, 4 (5%) in the
      INH and 7 (9%) in the placebo group. Among the TB cases, 5 were culture confirmed
      2 in the INH group and 3 in the placebo group, all susceptible to INH. Severe
      adverse events occurred rarely (n = 6; 2%). CONCLUSION: IPT is safe and well
      tolerated in HIV-infected children on concomitant ART. This study supports the
      need for a larger study to assess efficacy in HIV-infected children living in TB
      endemic areas.

PMID- 24670571
TI  - Diagnosis of paediatric tuberculosis using sputum induction in Botswana:
      programme description and findings.
AB  - SETTING: Four public hospitals in Botswana, a high tuberculosis (TB) burden
      setting. OBJECTIVES: To assess the feasibility and utility of sputum induction in
      the diagnosis of paediatric TB. DESIGN: From 2008 to 2010, children aged <=18
      years referred for suspected pulmonary TB underwent sputum induction. Confirmed
      TB was defined as the presence of at least one of the signs and symptoms
      suggestive of TB and positive Mycobacterium tuberculosis culture. Information on
      TB-associated symptoms (cough, fatigue, night sweats, low appetite, chest pain,
      weight loss, haemoptysis and contact with a TB case) was collected for three risk
      groups: human immunodeficiency virus (HIV) positive children, HIV-negative
      children aged <3 years and HIV-negative children aged >=3 years. RESULTS: The
      median age of the 1394 subjects who underwent sputum induction was 3.8 years (IQR
      1.3-8.4); 373 (27%) were HIV-positive, 419 (30%) were HIV-negative and 602 (43%)
      had unknown HIV status. TB was confirmed in 84 (6.0%); cases were more likely to
      have weight loss, chest pain or TB household contacts. There were no serious
      complications attributable to sputum induction during and after the procedure;
      only 0.8% (9/1174) of patients reported minor complications. CONCLUSIONS: In
      Botswana, paediatric sputum induction was feasible, safe and assisted
      bacteriological confirmation in a subgroup of children treated for TB.

PMID- 24670572
TI  - Determinants of tuberculosis treatment completion among newborns in a high-burden
      setting.
AB  - BACKGROUND: Newborns exposed to Mycobacterium tuberculosis are at high risk of
      progression to tuberculosis (TB) disease. DESIGN AND SETTING: A prospective
      cohort study conducted in Cape Town, South Africa, from January 2011 to June
      2012. TB-exposed newborns requiring isoniazid preventive therapy (IPT) or anti
      tuberculosis treatment were followed to 6 months of age. Appropriate tuberculosis
      treatment referral, maternal and socio-economic determinants were evaluated. The
      primary outcome, completion of treatment (6 months IPT, 3 months IPT with a
      negative tuberculin skin test, or 6 months' treatment for disease) was measured
      at 6 months. Data were collected from folders and care giver interviews. Cox
      regression was used to determine hazard ratios (HR) for non-completion of
      treatment. RESULTS: Fifty-six (63% human immunodeficiency virus [HIV] exposed) TB
      exposed newborns were included; median gestational age and mean birth weight were
      respectively 36 weeks and 2242 g. Of the 56 newborns, 44 (79%) were followed to 6
      months; 29/44 (66%) completed anti-tuberculosis treatment without study team
      intervention. Appropriate treatment referral was associated with a lower hazard
      of non-completion of treatment (unadjusted HR 0.34, 95%CI 0.12-0.93). This
      relationship was maintained in multivariable adjustment for maternal HIV status
      and type of care giver (adjusted HR 0.26, 95%CI 0.09-0.77). CONCLUSIONS:
      Appropriate anti-tuberculosis treatment referral improves completion of treatment
      in infants.

PMID- 24670573
TI  - Clinical significance of residual lesions in chest computed tomography after anti
      tuberculosis treatment.
AB  - OBJECTIVE: To evaluate the clinical significance of residual lesions in chest
      computed tomography (CT) findings at the end of anti-tuberculosis treatment.
      METHODS: We retrospectively reviewed 66 newly diagnosed patients with pulmonary
      tuberculosis (PTB) who were proven bacteriologically and/or histologically
      between March 2009 and December 2011. All patients were treated with standard
      short-course chemotherapy. Chest CT scans were performed before and after
      treatment. We assessed the residual lesions according to the response to
      treatment: possible active, equivocal and no active lesions. RESULTS: The most
      common CT finding before anti-tuberculosis treatment was bronchogenic spreading
      inflammation, such as the tree-in-bud appearance. After completion of anti
      tuberculosis treatment, regression of the initial parenchymal findings was found
      in all types of PTB lesions except consolidations. According to the treatment
      response, 33 (50%) patients had possible active lesions, 5 (8%) had equivocal
      lesions and 28 (42%) had no active lesions. However, no lesions progressed during
      a median follow-up of 15 months (interquartile range 10-21 months) after
      treatment completion, and no patient relapsed during this period. CONCLUSIONS: If
      initial parenchymal lesions regressed after sufficient TB treatment, residual
      lesions were not suggestive of persistent activity or the possibility of early
      relapse of PTB.

PMID- 24670574
TI  - Hepatotoxicity of anti-tuberculosis chemotherapy in patients with liver
      cirrhosis.
AB  - OBJECTIVE: To determine whether liver cirrhosis patients are at higher risk for
      drug-induced hepatotoxicity (DIH) than control subjects during treatment for
      tuberculosis (TB) with standard short-course regimens containing isoniazid (INH),
      rifampicin (RMP), ethambutol (EMB) and/or pyrazinamide (PZA). METHODS: Fifty
      liver cirrhosis patients with newly diagnosed active TB treated with INH, RMP,
      EMB and/or PZA were included in the study, along with 147 patients without liver
      disease selected as control subjects. DIH was defined as alanine aminotransferase
      (ALT) > 120 IU/l with hepatitis symptoms or ALT > 200 IU/l. RESULTS: The
      aetiology of the liver cirrhosis patients consisted of alcoholic liver cirrhosis
      (n = 37, 74%), hepatitis B (n = 10, 20%) and hepatitis C (n = 3, 6%). The mean
      Child-Pugh score of all liver cirrhosis patients was 7.0 +/- 1.2. DIH was more
      frequently found in liver cirrhosis patients, but the difference was not
      statistically significant (8.0% vs. 2.7%, P = 0.115). INH and RMP were
      successfully rechallenged and maintained until the end of treatment in three of
      four liver cirrhosis patients with DIH. CONCLUSION: Although DIH developed more
      frequently in TB patients with liver cirrhosis, the apparent difference in the
      incidence of DIH did not achieve statistical significance. Most of the patients
      with DIH were successfully treated with a standard short-course regimen including
      INH and RMP.

PMID- 24670575
TI  - Impact of chronic renal failure on anti-tuberculosis treatment outcomes.
AB  - SETTING: National Referral Centre for Tuberculosis (TB), Tehran, Iran. OBJECTIVE:
      To determine the impact of chronic renal failure (CRF) on TB treatment outcomes.
      DESIGN: A retrospective study was conducted among adult TB patients with CRF and
      age- and sex-matched TB controls without CRF treated at the National Research
      Institute of Tuberculosis and Lung Disease from 2004 to 2011. Multivariate
      analysis was performed to determine the impact of CRF on drug-induced hepatitis
      (DIH), treatment failure and all-cause mortality. RESULTS: A total of 55 TB cases
      with CRF and 165 TB cases without CRF were included in the study. Baseline
      demographic and clinical characteristics were similar, except that TB cases with
      CRF were more likely to be of Iranian nationality (94.5% vs. 83%, P = 0.04).
      During anti-tuberculosis treatment, 40 (18.2%) patients developed DIH, none
      failed treatment and 15 (6.8%) died. Patients with CRF were more likely to
      develop DIH (27.3% vs. 15.2%, P = 0.04) and to die during treatment (16.4% vs.
      3.6%, P = 0.001). CRF remained significantly associated with all-cause mortality
      (HR 4.87, 95%CI 1.73-13.65) in multivariate analysis, whereas the relationship
      with DIH was not. CONCLUSION: TB patients with CRF are at increased risk of
      death. More intensive monitoring of patients with CRF should be considered by the
      National TB Programme.

PMID- 24670576
TI  - Diagnostic dilemma: treatment outcomes of tuberculosis patients with inconsistent
      rifampicin susceptibility.
AB  - OBJECTIVE: A retrospective clinical trial to evaluate treatment outcomes in
      adults with smear-positive tuberculosis (TB) and discordant rifampicin (RMP)
      resistance results. DESIGN: A total of 2156 smear-positive TB patients underwent
      both conventional and Genechip drug susceptibility testing (DST) for RMP
      resistance. All 49 patients with discordant results treated with either a first
      line or second-line regimen were analysed. RESULTS: Of 30 Type I cases (Genechip
      resistant, conventional DST-susceptible) receiving the first-line regimen, 4 had
      a favourable outcome and 5 failed treatment. The 21 remaining Type I cases were
      treated with the second-line regimen, of whom 18 had a favourable outcome. Second
      line regimen thus resulted in significantly more favourable outcomes than first
      line treatment (P = 0.032). Among Type II cases (Genechip-susceptible,
      conventional DST-resistant), 13/19 received the first-line regimen, and 7 had a
      favourable outcome. The six Type II cases treated with the second-line regimen
      all had favourable outcomes. CONCLUSION: Patients with discordant RMP DST results
      who receive second-line regimens may have a better clinical response than those
      treated with the first-line regimen. Patients infected with fluoroquinolone
      resistant Mycobacterium tuberculosis strains were observed to have a
      significantly higher treatment failure rate.

PMID- 24670577
TI  - Effect of inhalers on the development of haemoptysis in patients with non-cystic
      fibrosis bronchiectasis.
AB  - BACKGROUND: The association of inhaler use with haemoptysis has rarely been
      reported in patients with non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE: To
      elucidate the effect of inhaler use on the development of haemoptysis in patients
      with non-CF bronchiectasis. METHODS: In a case-crossover study of 192 non-CF
      bronchiectasis patients with a history of haemoptysis and inhaler use, the risk
      of haemoptysis associated with the use of inhalers was elucidated. Two inhaled
      corticosteroids/long-acting beta2-agonists (ICS/LABA), one long-acting muscarinic
      antagonist and one short-acting beta2-agonist (SABA) were evaluated. The case and
      control periods were defined respectively as 030 and 180210 days before
      haemoptysis. RESULTS: The risk of haemoptysis during the case period was 3.51
      times higher than during the control period with any use of inhalers (95%CI
      1.966.28). The results of clinically significant haemoptysis showed good
      agreement with those of total events. These associations were consistent with the
      sensitivity analyses. In the sub-analysis according to inhaler type, ICS/LABA and
      SABA were significantly associated with an increased risk of haemoptysis (aOR
      2.62, 95%CI 1.255.45; aOR 2.51, 95%CI 2.235.15). CONCLUSIONS: In patients with
      non-CF bronchiectasis, the use of inhalers, especially including 2-agonist, was
      associated with an increased risk of haemoptysis.

PMID- 24670578
TI  - Evaluation of asthma control using Global Initiative for Asthma criteria and the
      Asthma Control Test in Uganda.
AB  - SETTING: Chest clinic of a national referral hospital in a resource-limited
      country. OBJECTIVES: To determine the level of asthma control, factors
      influencing asthma control and the accuracy of the Asthma Control Test (ACT).
      DESIGN: We collected demographic and clinical data and administered the Global
      Initiative for Asthma (GINA) criteria test and the ACT. The proportions of
      patients in each of the GINA and ACT control categories (uncontrolled, partly
      controlled and well controlled) were calculated. Multivariate analysis was
      performed to identify factors associated with asthma control. Diagnostic test
      parameters for the ACT using GINA criteria as gold standard were calculated.
      RESULTS: Of 88 asthma patients enrolled, 67% were female. The median age was 34
      years (range 12-85). Using GINA criteria, respectively 59 (67%), 17 (19%) and 12
      (14%) patients had uncontrolled, partly controlled and well controlled asthma;
      per ACT, the corresponding figures were respectively 40% (35/88), 43% (38/88) and
      17% (15/88). ACT sensitivity, specificity, positive predictive and negative
      predictive value were respectively 95%, 92%, 99% and 73%. Nasal congestion was
      associated with uncontrolled asthma (P = 0.031). CONCLUSION: The majority of the
      patients at the Mulago Hospital have inadequately controlled asthma, and this is
      associated with nasal congestion. A simple symptom questionnaire, the ACT, can
      correctly classify asthma control.

PMID- 24670579
TI  - Active case finding for tuberculosis: what is the most informative measure for
      policy makers?

PMID- 24670580
TI  - In reply to 'Active case finding for tuberculosis: what is the most informative
      measure for policy makers?'.

PMID- 24670581
TI  - Aflatoxin regulations and global pistachio trade: insights from social network
      analysis.
AB  - Aflatoxins, carcinogenic toxins produced by Aspergillus fungi, contaminate maize,
      peanuts, and tree nuts in many regions of the world. Pistachios are the main
      source of human dietary aflatoxins from tree nuts worldwide. Over 120 countries
      have regulations for maximum allowable aflatoxin levels in food commodities. We
      developed social network models to analyze the association between nations'
      aflatoxin regulations and global trade patterns of pistachios from 1996-2010. The
      main pistachio producing countries are Iran and the United States (US), which
      together contribute to nearly 75% of the total global pistachio market. Over this
      time period, during which many nations developed or changed their aflatoxin
      regulations in pistachios, global pistachio trade patterns changed; with the US
      increasingly exporting to countries with stricter aflatoxin standards. The US
      pistachio crop has had consistently lower levels of aflatoxin than the Iranian
      crop over this same time period. As similar trading patterns have also been
      documented in maize, public health may be affected if countries without aflatoxin
      regulations, or with more relaxed regulations, continually import crops with
      higher aflatoxin contamination. Unlike the previous studies on maize, this
      analysis includes a dynamic element, examining how trade patterns change over
      time with introduction or adjustment of aflatoxin regulations. 

PMID- 24670582
TI  - Relationship between BaTiO3 nanowire aspect ratio and the dielectric permittivity
      of nanocomposites.
AB  - The aspect ratio of barium titanate (BaTiO3) nanowires is demonstrated to be
      successfully controlled by adjusting the temperature of the hydrothermal growth
      from 150 to 240  degrees C, corresponding to aspect ratios from 9.3 to 45.8,
      respectively. Polyvinylidene fluoride (PVDF) nanocomposites are formed from the
      various aspect ratio nanowires and the relationship between the dielectric
      constant of the nanocomposite and the aspect ratio of the fillers is quantified.
      It was found that the dielectric constant of the nanocomposite increases with the
      aspect ratio of the nanowires. Nanocomposites with 30 vol % BaTiO3 nanowires and
      an aspect ratio of 45.8 can reach a dielectric constant of 44.3, which is 30.7%
      higher than samples with an aspect ratio of 9.3 and 352% larger than the polymer
      matrix. These results demonstrate that using high-aspect-ratio nanowires is an
      effective way to control and improve the dielectric performance of nanocomposites
      for future capacitor applications. 

PMID- 24670583
TI  - Depression and bullying in children.

PMID- 24670584
TI  - Management of transient ischaemic attack: the importance of time and specialised
      clinics.

PMID- 24670585
TI  - Pacific Islands Families Study: depressive symptoms in 9-year-old Pacific
      children living in New Zealand.
AB  - AIM: This study investigated associations between individual, maternal, cultural
      and socio-demographic variables with symptoms of child depression in 9-year-old
      Pacific children living in New Zealand. METHOD: The longitudinal Pacific Islands
      Families (PIF) Study is following a cohort of Pacific children born in Auckland,
      New Zealand, in 2000. At approximately 9 years postpartum, child self-reports
      (n=858) of depressive symptoms were gathered. RESULTS: Being a victim or
      perpetrator of bullying, previous internalising behaviour problems and low
      maternal education were significantly associated with high child depression
      scores. Low depression scores were associated with children's positive perception
      of self, physical abilities, parental and peer relationships, high verbal
      intelligence, and high performance at school. CONCLUSION: These findings indicate
      that building up child self-esteem and supportive relationships around the child
      are likely to reduce the risk of depression and these strengths may mitigate
      against bullying involvement.

PMID- 24670586
TI  - Changes in the provision of transient ischaemic attack services in New Zealand
      2008 to 2013.
AB  - BACKGROUND: Urgent assessment and management of patients with transient ischaemic
      attack (TIA) reduces the early risk of stroke. In 2008 an audit was conducted of
      TIA services in New Zealand and a substantial discrepancy was found between
      clinical practice and recommendations in TIA guidelines. We aimed to re-evaluate
      the situation again in 2013 to determine if there had been any change in
      provision of TIA services. METHODS: A brief written questionnaire, based on the
      2008 survey, was sent to lead stroke clinicians at all district health boards.
      Questions were asked about the provision of services, including investigation and
      management of patients with TIA. RESULTS: The questionnaire was completed by all
      DHBs. The number of DHBs with a dedicated TIA clinic has increased from 3 in 2008
      to 15 in 2013 and the number with a clinical pathway for assessment of patients
      with TIA has increased from 5 to 17. Brain and carotid imaging is usually
      available within 48h for patients assessed as having high stroke risk. Delays for
      other patients remain frequent for brain imaging in 14 DHBs and for carotid
      imaging in 16 DHBs. There was a decrease in the number of DHBs with a wait of
      more than a week for carotid endarterectomy when indicated from 16 in 2008 to 4
      in 2013. CONCLUSION: There have been significant improvements in the provision of
      TIA services over the last 5 years. However in order to reduce the burden of
      stroke, DHBs need to consider further investments into adequately resourced TIA
      services as a priority.

PMID- 24670587
TI  - Sex workers' utilisation of health services in a decriminalised environment.
AB  - BACKGROUND: In 2003 the Prostitution Reform Act (PRA) was passed in New Zealand
      which decriminalised all activities associated with sex work. AIM: To explore sex
      workers' utilisation of health services in New Zealand following
      decriminalisation of sex work and disclosure of their occupation to health
      professionals. METHOD: A cross-sectional survey was carried out with 772 sex
      workers and in-depth interviews were carried out with 58 sex workers in New
      Zealand. RESULTS: Most sex workers have regular sexual health check-ups and most
      access their general practitioner (GP) for both general health needs (91.8%) and
      sexual health needs (41.3%). A quarter of the participants accessed a local
      sexual health centre for their sexual health needs and just over 15% accessed New
      Zealand Prostitutes' Collective's (NZPC's) Sexual Health Clinic. Little change
      was found in disclosure of occupation to health professionals following
      decriminalisation. Sex workers remain concerned about disclosing their occupation
      because of perceived stigma attached to their occupation. CONCLUSION: Most sex
      workers have regular sexual health check-ups and most access their GP for this
      service. However, because of on-going perceptions of stigmatisation many do not
      report their occupation to their GP which may mean that check-ups may not be
      comprehensive. For this reason, sexual health check-ups performed at NZPC may be
      preferable to check-ups elsewhere because disclosure of occupation is not an
      issue.

PMID- 24670588
TI  - Outcomes in HrHPV-positive women with low grade cervical smears and normal or low
      grade initial colposcopy results.
AB  - AIM: To determine outcomes in HrHPV-positive women with low grade cervical smears
      and normal or low grade initial colposcopy biopsy results in a cohort of women
      over a 2-year follow-up period. BACKGROUND: The revised National Cervical
      Screening (NCS) programme guidelines in New Zealand were implemented in October
      2009. The guidelines state that women 30 years and older should undergo reflex
      HPV testing. If this test confirms the presence of HrHPV, women are to be
      referred for a colposcopic assessment. The guidelines do not mention what the
      follow-up period should be of women with HrHPV and normal or low grade
      abnormalities at colposcopy/biopsy. METHOD: In this study we followed up women 30
      years and older referred to Wellington Hospital from 1/10/2009 to 1/10/2011 with
      a LGSIL or ASC-US smear and positive HrHPV test. Those with a normal or low grade
      biopsy result were followed over a 2-year period to determine outcomes. RESULTS:
      Our study found that 4% of women with initial normal biopsy results and 15.2%
      with initial low grade results had progressed to high grade (CIN 2/3/invasion)
      over a 2-year follow-up period. During the same time period, 68% of women with an
      initial normal biopsy and 61% with a low grade biopsy had a normal colposcopy
      after 2 years. Twenty-eight percent of women with normal and 24% of those with
      initial with low grade biopsy continued to have LG abnormalities at 2 years of
      follow-up. CONCLUSION: Women 30 years and older who are HrHPV-positive and have
      low grade abnormalities at colposcopic biopsy may be followed up with a 12-month
      cervical smear rather than repeat colposcopy as the risk of progression to a high
      grade abnormality is low.

PMID- 24670589
TI  - Using triggers in primary care patient records to flag increased adverse event
      risk and measure patient safety at clinic level.
AB  - AIM: Using triggers to identify adverse events is proposed as an efficient means
      of consistently measuring, and tracking events that result in harm to patients.
      We aimed to test whether using triggers in our large provincial general practice
      could provide meaningful directions for improving safety. METHOD: A literature
      review identified potential triggers and established the number of patients whose
      records we should review. Two teams independently reviewed 170 randomly selected
      patients' records for trigger presence and for evidence of harm relating to that
      trigger. All triggers were tested for sensitivity and specificity: triggers with
      low specificity were removed. Logistic regression was used on both initial and
      refined trigger sets to measure the odds ratio (OR) of harm occurring if a
      trigger was present. RESULTS: Initially 36 triggers were identified. Applying
      these to 109.6 patient-years of records for 170 patients, we identified harm in
      the records of 46 (27.1%) patients. There were 7 occurrences of harm per 100
      consultations (harm rate per consultation=0.07 (95% confidence interval [CI] 0.05
      0.09) and 41 per 100 consulting patient years (95%CI 29-55). All harms related to
      medication use. The initial triggers were sensitive (0.98) but non-specific
      (0.08): removing triggers with low specificity left only 8. The OR for harm
      occurring using the initial triggers was 4.0 (95% 0.5-30) and using the refined
      trigger set OR=6.3 (95%CI 2.7-14.8). CONCLUSION: 8 selected triggers are a useful
      way of measuring progress towards safer care for patients in primary care
      practice.

PMID- 24670590
TI  - Work status and disability trajectories over 12 months after injury among workers
      in New Zealand.
AB  - AIM: To describe work and disability trajectories over 12 months following injury
      among workers. METHODS: Workers injured at work or elsewhere (n=2626) were
      sourced from the Prospective Outcomes of Injury Study, a longitudinal cohort
      study in New Zealand, with the primary objective of identifying factors
      associated with disability following injury. Work and disability status was
      assessed at 3- and 12-months post injury. The measure of disability was the brief
      WHODAS II 12-item instrument. Participants were dichotomised into 'disability' or
      'no disability' groups based on whether their WHODAS score was greater than, or
      equal to, 10. In terms of 12-month work status, there are 16 different scenarios.
      These were grouped into 4 categories: sustained work (SW), delayed return to work
      (RTW), non-sustained RTW, and sustained off-work. RESULTS: We had complete
      information for 1975 workers. The largest group (68%) was SW, 32% of which had
      disability at either time point. The second largest group consisted of 17% of
      workers who were classified as delayed RTW, 76% of whom were disabled at either
      time point. Among the non-sustained RTW group (7%), 52% had disability at either
      time point. Of the sustained off-work group (8%), 80% were disabled at either 3-
      or 12-months. CONCLUSION: Although return to work is a useful provider
      performance indicator of injury compensation and rehabilitation it is inadequate
      from a wider societal perspective and needs to be complemented by other important
      outcome measures such as disability status.

PMID- 24670591
TI  - Acute liver dysfunction as a presentation of haemophagocytic lymphohistiocytosis.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is an uncommon disorder of histiocyte
      function which presents with fever, cytopaenias and end-organ dysfunction. We
      report the case of a 62-year-old man with acute liver dysfunction as an initial
      presentation of HLH. 

PMID- 24670592
TI  - Medical image. Adult intussusception as a cause of chronic intermittent abdominal
      pain.

PMID- 24670593
TI  - Medical image. Adrenocortical carcinoma presenting with hirsutism: an uncommon
      cause of a common complaint.

PMID- 24670594
TI  - Consumption of vitamin C is below recommended daily intake in many cancer
      patients and healthy volunteers in Christchurch.

PMID- 24670595
TI  - Wise use of antibiotics.

PMID- 24670596
TI  - The taxing of fizzy drinks.

PMID- 24670597
TI  - Comment on "why do patients choose the emergency department?".

PMID- 24670598
TI  - Question time.

PMID- 24670600
TI  - [In Process Citation].

PMID- 24670601
TI  - [In Process Citation].
AB  - The biosynthesis of steroid hormones is a fascinating process . In this reaction
      cascade, cholesterol, a normal constituent of the lipid membrane bylayers, is
      coverted through a number of hydroylation, oxidation and reduction steps into a
      variety of biologically active substances, such as mineralocorticoids,
      glucocorticoids and sex hormones. Most of these modifications take place in the
      adrenal glands, testes and ovaries, although other tissues such as liver, kidney,
      placenta, brain, and skin are also quite active. The effect of steroid hormones
      is a complex, not yet fully understood process in which steroid hormones bind to
      specific intracellular receptors in the target cells, so that interactions with
      DNA in the nucleus are possible. What follows is a modulation of gene activity
      and a hormone- specific reaction occurs (1). Physiologically, sex hormones are
      important in every stage of life, from determining the sex differentiation, to
      the phenotypic differentiation in a female or male individual. They are also
      essential for a successful reproductive life and are involved in the development
      of the brain and the expression of gender specific behavior. Anomalies in each
      step of steroid hormone action have potential clinical consequences.
      Abnormalities in the receptor or post-receptor machinery lead to disturbances of
      the effect of a particular hormone. However, abnormalities of steroid hormone
      production can also lead to serious and complex effects. For example,the
      consequences of a block in the steroid synthesis ate twp-fold: on the one hand
      the lack of products has dramatic consequences in the development and function of
      the target organs; on the other hand the accumulation of the hormone upstream the
      block will cause the activation of other members of the steroid hormone receptor
      family. Both conditions can cause complex clinical pictures. 

PMID- 24670599
TI  - PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells.
AB  - Retinoids are micronutrients that are stored as retinyl esters in the retina and
      hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic
      liver diseases. The enzyme responsible for hydrolysis and release of retinyl
      esters from HSCs is unknown and the relationship between retinoid metabolism and
      liver disease remains unclear. We hypothesize that the patatin-like phospholipase
      domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs.
      We tested our hypothesis both in primary human HSCs and in a human cohort of
      subjects with non-alcoholic fatty liver disease (N = 146). Here we show that
      PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol
      availability and insulin, and increased PNPLA3 expression results in reduced
      lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs
      in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes
      retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic
      activity is markedly reduced with purified PNPLA3 148M, a common mutation
      robustly associated with liver fibrosis and hepatocellular carcinoma development.
      We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a
      multivariate analysis) determinant of circulating retinol-binding protein 4, a
      reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a
      lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans.
      Importantly, this indicates a potential novel link between HSCs, retinoid
      metabolism and PNPLA3 in determining the susceptibility to chronic liver disease.

PMID- 24670602
TI  - [In Process Citation].
AB  - Bone is a dynamic tissue that undergoes renewal and repair throughout life
      through the process of bone remodelling. Skeletal homeostasis is achieved through
      coupled and balanced bone resorption and bone formation. Several local and
      systemic factors regulate these processes, including sex hormones. Estrogenes and
      androgens influence growth, maturation and maintenance of bone mass. Sex homones
      act on bone through multiple mechansims. Sex hormones influence synthesis and
      secretion of many growth factors and cytokines, and play therefore a central role
      in the regulation of bone metabolism. The local and systemic regulation of bone
      metabolism occurs through fine tuned processes, which are influences by sex
      hormones and the aging process. This is evidenced by the fact that hypogonadims
      in both sexes is associated with bone loss an estrogen deficiency at the
      menopause is an important pathophysiological factor in the developement of
      postmenopausal osteoporosis. Treatment with aromatese inhibitors for breast
      cancer and antiandrogen treatment for prostate cancer are associated with an
      increased fracture risk and warrant increased diagnostic and treatment awareness.

PMID- 24670603
TI  - [In Process Citation].
AB  - Diagnosis and therapy of male hypogonadism is still a challenge because of the
      unspecific clinical signs and symptoms. The clinical presentation of a androgen
      deficiency is age-related. In the adult men, one can often observe fatigue,
      decrease in physical capacity, loss of libido and erectile dysfunction. At the
      physical examination, genitalia have always to be assessed in search of a
      testes/penis atrophy. Two fasting measurements of total testosterone
      concentrations by a reliable assay are needed to confirm the diagnosis. By
      assessing gonadotropines the origin of hypogonadism can be determined
      (central/secondary or peripheral/primary). Exogenous administration of androgens
      should be considered in young, sportive, healthy and muscular males. Patients
      with metabolic syndrome should only be screened for hypogonadism in the presence
      of suggestive symptoms. Prostate disease, hematocrit higher than 50 %,
      uncontrolled heart failure and severe obstructive sleep apnea are
      contraindications of a testosterone replacement therapy. Patients with metabolic
      syndrome-associated low testosterone levels should firstly benefit from a
      lifestyle intervention that can normalize clinical and biochemical hypogonadism.
      So far, there is no clear evidence for a possible benefit of testosterone therapy
      in patients with the metabolic syndrome. Similarly, in patients with PADAM
      (partial androgen deficiency of the aging male) testosterone therapy is not
      established or recommended. 

PMID- 24670604
TI  - [In Process Citation].
AB  - The definition of late onset hypogonadism in the aging male is controversially
      debated, and according to the latest literature consists of at least three
      especially sexual symptoms such as loss of morning erection, low sexual desire
      and erectile dysfunction as well as a total testosterone < 8 - 11 nmol/l.
      Testosterone replacement therapy in the aging male has been shown to have a
      beneficial effect on muscle and fat mass as well as on bone mineral density, with
      more conflicting effects observed on muscle strength, sexual function, mood and
      quality of life. The prescriptions for testosterone products for the indication
      of the aging male were increased over 170 % in the previous 5 years. Furthermore,
      there are many epidemiological data showing an inverse relationship between
      testosterone levels and obesity, insulin resistance, the metabolic syndrome and
      type 2 diabetes mellitus. However, only few small randomized placebo-controlled
      studies have investigated the effect of testosterone replacement therapy on
      insulin resistance and HbA1c levels, with controversial results. Importantly, so
      far the long-term safety and efficacy of testosterone replacement therapy has not
      been established. Although until now no clear evidence was found that
      testosterone replacement therapy has a causative role in prostate cancer or
      indeed changes the biology of the prostate, in a recent meta-analysis a 4-fold
      increased risk of prostate-associated event rates in testosterone treated elderly
      men sounds a note of caution. Also the risk for cardiovascular events is still
      not clear and caution is warranted especially in elderly men with cardiovascular
      disease and limited mobility. In summary, the actual available evidence of long
      term risks and outcome of testosterone replacement therapy is still very limited
      and carefully designed placebo-controlled trials of testosterone administration
      to assess the risks and benefits of such a therapy are required. Until then,
      testosterone treatment in elderly men should be restricted to elderly men with
      clearly low testosterone levels in the presence of clinical symptoms and
      advantages and disadvantages need to be accurately weighted. A careful monitoring
      of potential side effects is necessary. 

PMID- 24670605
TI  - [In Process Citation].
AB  - The publication of the first report of the Women's Health Inititiave in 2002,
      which evaluated the efficacy and the risks of substitution of postmenopausal
      women with estrogens and gestagens, has exerted a profound negative impact on the
      utilization of hormonal treatment. On the one hand, the WHI-studies have left
      both the medical community and the patients community in a state of anxiety and
      uncertainty, on the other has an entire set of differentiated and clarifying post
      hoc analyses contributed to re-define the role and the safety of hormonal
      treatment of menopausal women and the preventive effect on osteoporotic fractures
      has remained uncontested. As a result, new protocols based on lower dosages with
      new combinations of endocrine products allow for an early start of hormonal
      substitution in menopause within the so-called "window of opportunity" thereby
      not only ameliorating the climacteric symptoms but also preventing the early
      onset of cardiovascular disease. In addition, the risk of invasive breast cancer
      can now be better quantified, whereas participation in a mammographic screening
      programme helps to improve the safety of the treatment. 

PMID- 24670606
TI  - [In Process Citation].
AB  - BACKGROUND: Over the last years, various revelations demonstrated that the doping
      problem is far from being solved. These included the American cyclist Lance
      Armstrong's disclosure and subsequent conviction for doping abuse over a period
      of many years. Furthermore, these revelations underlined the importance of strong
      and independent national antidoping agencies (NADA). During the current revision
      process of the World Anti-Doping Programme (WADP), Antidoping Switzerland is
      campaigning for national anti-doping agencies to have the same rights, the same
      authority and the same degree of responsibility as international sports
      associations. Further, the newly revised Federal Act on the Promotion of Sport
      and Exercise (Sport Promotion Act), which entered into force on 1 October 2012,
      establishes the framework for cooperation with customs officers when suspected
      doping substances are seized. By the end of 2012 Antidoping Switzerland received
      about 50 reports from the customs authorities, and in 24 cases an administrative
      ruling for the seizure and destruction of these doping substances was issued. In
      addition, there was also a greater cooperation between customs and the Swiss
      Agency for Therapeutic Products Swissmedic. Two athletes have already been
      sanctioned under private law for importing doping substances. CONTROLS:
      Antidoping Switzerland carried out 2'551 controls in 2012. Of these, 1'752 were
      urine tests, of which 1'089 were conducted out of competition and 663 in
      competition. The majority of the 799 blood controls were conducted out of
      competition. In 2012 Antidoping Switzerland lodged about 20 applications on
      violations of the anti-doping provisions with Swiss Olympic's Disciplinary
      Chamber for Doping Cases (DC). In numbers, four athletes were banned for two
      years for using anabolic steroids. A trainer was also suspended for two years for
      having given an athlete a stimulant before a competition. 2012 was the first year
      in which two athletes were convicted of import of doping substances (EPO and an
      anabolic drug respectively) on information provided by customs officers. Both
      athletes were banned from competition for two years. Legal basis: Of importance
      to all the physicians looking after athletes is to know the actual legal basis:
      The international law basis of the Swiss fight against doping are the Council of
      Europe Convention against Doping of 16 November 1989 and the International
      Convention against Doping in Sport of the General Conference of the United
      Nations Educational, Scientific and Cultural Organization (UNESCO) of 19 October
      2005. The basis in public law of the Swiss fight against doping is the Federal
      Act on the Promotion of Gymnastics and Sport of 17 March 1972. Article 11e,
      paragraph 1 states that "national sport organisations, the relevant umbrella
      bodies and bodies responsible for sporting events that are supported in the
      framework of this act [...] are required to ensure that the necessary doping
      controls are carried out in their area of responsibility". Article 11 f,
      paragraph 1 of the Federal Act also states that "whoever produces, introduces,
      transfers, sells, prescribes or provides substances for doping purposes or who
      uses methods for doping purposes for third persons will be liable to a prison
      sentence or to a fine of up to 100'000 francs". The civil law basis of the Swiss
      fight against doping consists of the norms established by various actors in the
      sporting world. These actors are in most cases clubs, associations and
      foundations in accordance with the stipulations of the Swiss civil code. The
      Swiss Olympic Association's revised Doping Statute was approved by the Sports
      Parliament on 15 November 2008. The statute implements the code of the World Anti
      Doping Agency (WADA) in Switzerland. In the introduction it defines the anti
      doping agencies in our country: Antidoping Switzerland and the Disciplinary
      Chamber for Doping Offences of the Swiss Olympic Association. The revised Statute
      entered into force on 1 January 2009. Finally, it is well known that the use of
      anabolic steroids and other doping substances is a phenomenon not restricted to
      professional sport only. Also in popular sport, in particular in fitness, the use
      of anabolic steroids to increase physical performance is very common. To
      summarize, doping is a widespread phenomenon not only in athletes. In these
      situations physicians involved have to know not only the medical but also the
      legal side of prescribing, applying substances to persons actively involved in
      sport activities. Otherwise it might happen that wittingly or unwittingly the
      doctor runs into serious problems. All the most valuable information are
      published at http://www.antidoping.ch.

PMID- 24670607
TI  - The role of high-dose chemotherapy in the management of germ cell tumors.
AB  - PURPOSE OF REVIEW: To discuss the current role and future perspectives of high
      dose chemotherapy (HDCT) in the management of advanced germ cell tumors (GCTs).
      RECENT FINDINGS: Multiple studies have demonstrated the safety and efficacy of
      HDCT, consisting of carboplatin and etoposide followed by stem cell reinfusion,
      for the salvage treatment of GCTs. However, three randomized trials showed no
      benefit for HDCT over conventional dose chemotherapy in the first-line setting.
      Similarly, adding a third drug to etoposide with carboplatin does not seem to
      substantially improve treatment efficacy and may increase toxicity and mortality.
      Recent retrospective data from single centers and a large international
      collaboration demonstrated better outcomes with use of HDCT in the initial
      (rather than later) salvage setting as well as with sequential rather than single
      cycle regimens. However, randomized data are lacking. Prognostic factors for
      outcome to salvage HDCT were recently established and enhanced supportive
      measures such as growth factors and antibiotic prophylaxis have resulted in a
      dramatic decrease in morbidity and mortality. SUMMARY: HDCT plays an integral
      role in the salvage treatment of patients with advanced GCTs. However, optimal
      timing (initial vs. later salvage), dosing, number of high-dose cycles, and
      patient selection remain to be defined.

PMID- 24670608
TI  - Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade
      glioma.
AB  - BACKGROUND: A phase II trial was performed to evaluate the efficacy of a dose
      dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent
      high-grade gliomas (HGG). METHODS: Sixty patients with recurrent HGG received
      temozolomide at 150 mg/m(2)/day on days 1-7 and days 15-21 during each 4-week
      cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a
      secondary endpoint of overall survival (OS). A further exploratory objective
      included the investigation of whether methylation status of the O(6)
      methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted
      outcomes. RESULTS: Among patients with glioblastoma (n = 40), PFS-6 was 10% (95%
      CI, 3%-24%) with median OS of 21.6 weeks (95% CI, 16.9-30.6 weeks). PFS-6 for
      grade III glioma patients (n = 20) was 50% (95% CI, 27%-73%), and median OS was
      100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer
      PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P =
      .07 for OS). Additionally, bevacizumab-naive glioblastoma patients had
      significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to
      not reached] vs 7.57 weeks [95% CI, 7.29-8.29 weeks], log-rank test, P < .001;
      median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9-27.3
      weeks], log-rank test, P < .001). CONCLUSIONS: The dose-dense temozolomide
      regimen was well tolerated, although it has no significant activity in this
      population. Clinical trials.gov identified. NCT00619112 (available at
      http://clinicaltrials.gov/ct2/show/NCT00619112).

PMID- 24670610
TI  - A novel electrospun nerve conduit enhanced by carbon nanotubes for peripheral
      nerve regeneration.
AB  - For artificial nerve conduits, great improvements have been achieved in mimicking
      the structures and components of autologous nerves. However, there are still some
      problems in conduit construction, especially in terms of mechanical properties,
      biomimetic surface tomography, electrical conductivity and sustained release of
      neurotrophic factors or cells. In this study, we designed and fabricated a novel
      electrospun nerve conduit enhanced by multi-walled carbon nanotubes (MWNTs) on
      the basis of a collagen/poly(epsilon-caprolactone) (collagen/PCL) fibrous
      scaffold. Our aim was to provide further knowledge about the mechanical effects
      and efficacy of MWNTs on nerve conduits as well as the biocompatibility and
      toxicology of MWNTs when applied in vivo.The results showed that as one
      component, carboxyl MWNTs could greatly alter the composite scaffold's
      hydrophilicity, mechanical properties and degradability. The electrospun fibers
      enhanced by MWNTs could support Schwann cell adhesion and elongation as a
      substrate in vitro. In vivo animal studies demonstrated that the MWNT-enhanced
      collagen/PCL conduit could effectively promote nerve regeneration of sciatic
      nerve defect in rats and prevent muscle atrophy without invoking body rejection
      or serious chronic inflammation. All of these results showed that this MWNT
      enhanced scaffold possesses good biocompatibility and MWNTs might be excellent
      candidates as engineered nanocarriers for further neurotrophic factor delivery
      research. 

PMID- 24670612
TI  - Movement deviation and asymmetry assessment with three dimensional gait analysis
      of both upper- and lower extremity results in four different clinical relevant
      subgroups in unilateral cerebral palsy.
AB  - BACKGROUND: In unilateral cerebral palsy, movement pattern can be difficult to
      define and quantify. The aim was to assess the degree of deviation and asymmetry
      in upper and lower extremities during walking. METHODS: Forty-seven patients, 45
      Gross Motor Function Classification Scale (GMFCS) I and 2 patients GMFCS II, mean
      age 17.1 years (range 13.1 to 24.0) and 15 matched controls were evaluated. Gait
      profile score (GPS) and arm posture score (APS) were calculated from three
      dimensional gait analysis (GA). Asymmetry was the calculated difference in
      deviation between affected and unaffected sides. FINDINGS: The GPS was
      significantly increased compared to the control group on the affected side (6.93
      (2.08) versus 4.23 (1.11) degrees) and on the unaffected side (6.67 (2.14)). The
      APS was also significantly increased on the affected side (10.39 (5.01) versus
      5.52 (1.71) degrees) and on the unaffected side (7.13 (2.23)). The lower
      extremity asymmetry increased (significantly) in comparison with the control
      group (7.89 (3.82) versus 3.90 (1.01)) and correspondingly in the upper extremity
      (9.75 (4.62) versus 5.72 (1.84)). The GPS was not different between affected and
      unaffected sides, however the APS was different (statistically significant).
      INTERPRETATION: We calculated deviation and asymmetry of movement during walking
      in unilateral CP, identifying four important clinical groups: close to normal,
      deviations mainly in the leg, deviations mainly in the arm and those with
      deviation in the arm and leg. This method can be applied to any patient group,
      and aid in diagnosing, planning treatment, and prognosis.

PMID- 24670611
TI  - Bone marrow-derived mononuclear cell transplantation in spinal cord injury
      patients by lumbar puncture.
AB  - PURPOSE: This study was conducted to assess the safety and feasibility of
      intrathecal transplantation of autologous bone marrow-derived mononuclear cells
      for the treatment of patients with spinal cord injury. METHODS: Ten patients were
      included in the study. Approximately 120 ml of bone marrow aspirate was obtained
      from bilateral iliac bone of patients with spinal cord injury. Isolation of
      mononuclear cells was performed using Ficoll density-gradient centrifugation.
      Bone marrow mononuclear cells were transplanted into cerebrospinal fluid by
      lumbar puncture. Functional tests were performed prior to the cell
      transplantation and six months after cell transplantation. The patients were
      carefully observed for up to six months. RESULTS: In 5 patients with AIS A prior
      to cell transplantation, 1 patient converted to AIS B six months after cell
      transplantation. In 5 patients with AIS B, 1 patient converted to AIS D and 2
      patients to AIS C. MRI did not show any complication. Two patients showed slight
      anemia after aspiration of bone-marrow cells, which returned to normal level
      within a several weeks. CONCLUSION: The results of this study suggest that this
      method may be safe and feasible.

PMID- 24670613
TI  - Case study of airborne fungi according to air temperature and relative humidity
      in houses with semi-basements adjacent to a forested hillside.
AB  - We studied airborne concentrations of fungal spores and the thermal environment
      in houses with semi-basements surrounded by a natural forest. We examined the
      relationship between airborne fungi and the thermal environment, surrounding
      natural environment, structures of houses and use of a dehumidifier. The subject
      residential area was located in the northern part of Nara city, Nara prefecture,
      Japan. Six detached houses were included in this study. In residential areas,
      outdoor airborne concentrations were high during summer and autumn, correlated
      with humidity. The presence of Basidiomycetes was particularly notable, although
      the indoor concentration was lower than the outdoor level. In the semi-basement
      rooms, relative humidity was nearly always >80% when the residence was built;
      however, both the indoor humidity and fungal concentrations decreased greatly
      when a dehumidifier was used in this study. High levels of Aspergillus and
      Basidiomycetes were detected in semi-basements. Basidiomycetes are likely of
      outdoor origin, whereas Aspergillus might grow indoors. Moreover, the composition
      of fungal species differed according to room-structure and usage. Due to the
      health risks associated with high indoor concentrations of fungi, the utilization
      of the semi-basement or basement space requires adequate ventilation and
      dehumidification, beginning immediately after construction. 

PMID- 24670609
TI  - Increased tryptophan uptake on PET has strong independent prognostic value in
      patients with a previously treated high-grade glioma.
AB  - BACKGROUND: Previously, we demonstrated the high accuracy of alpha-[(11)C]methyl
      L-tryptophan (AMT) PET for differentiating recurrent gliomas from radiation
      injury. The present study evaluated the prognostic value of increased AMT uptake
      in patients with previously treated high-grade glioma. METHODS: AMT-PET was
      performed in 39 patients with suspected recurrence of World Health Organization
      grades III-IV glioma following surgical resection, radiation, and chemotherapy.
      Mean and maximum standardized uptake values (SUVs) and unidirectional AMT uptake
      (K) were measured in brain regions suspicious for tumor and compared with the
      contralateral cortex (ie, background). Optimal cutoff thresholds for 1-year
      survival prediction were determined for each AMT parameter and used for
      calculating the prognostic value of high (above threshold) versus low (below
      threshold) values for post-PET overall survival (OS). RESULTS: In univariate
      analyses, 1-year survival was strongly associated with 3 AMT parameters (SUVmax,
      SUVmean, and tumor-to-background K-ratio; odds ratios: 21.3-25.6; P <= .001) and
      with recent change in MRI contrast enhancement (odds ratio: 14.7; P = .02).
      Median OS was 876 days in the low- versus 177 days in the high-AMT groups (log
      rank P < .001). In multivariate analyses, all 3 AMT parameters remained strong
      predictors of survival: high AMT values were associated with unfavorable 1-year
      survival (binary regression P <= .003) and shorter overall survival in the whole
      group (Cox regression hazard ratios: 5.3-10.0) and in patients with recent
      enhancement change on MRI as well (hazard ratios: 7.0-9.3; P <= .001).
      CONCLUSION: Increased AMT uptake on PET is highly prognostic for 1-year and
      overall survival, independent of MRI contrast enhancement and other prognostic
      factors in patients with a previously treated high-grade glioma.

PMID- 24670614
TI  - Bioremediation of heavily oil-polluted seawater by a bacterial consortium
      immobilized in cocopeat and rice hull powder.
AB  - We examined the effectiveness of cocopeat and rice hull powder obtained from
      agricultural wastes as biocarriers for an oil-degrading bacterial consortium.
      Scanning electron microscopy revealed colonization and strong attachment of
      bacterial cells on the surface of both carriers. Results of a 60-day in vitro
      seawater bioremediation trial showed significant oil reduction and high
      cultivable bacterial counts in treatments augmented with the carrier-attached
      bacterial consortia compared to treatments supplemented with the same consortium
      in free living and encapsulated forms. Significant degradations in both aliphatic
      and aromatic fractions were obtained in treatments augmented with carrier
      immobilized consortia. The developed immobilized cells showed sustained
      activities and viabilities during storage for six months. Results of this study
      demonstrated that inexpensive waste materials can be utilized as biocarriers of
      an oil-degrading consortium and that immobilization on biocarriers can enhance
      the bioremediation of oil-contaminated seawater. 

PMID- 24670615
TI  - Development of a PCR-based method for monitoring the status of Alcaligenes
      species in the agricultural environment.
AB  - To analyze the status of the genus Alcaligenes in the agricultural environment,
      we developed a PCR method for detection of these species from vegetables and
      farming soil. The selected PCR primers amplified a 107-bp fragment of the 16S
      rRNA gene in a specific PCR assay with a detection limit of 1.06 pg of pure
      culture DNA, corresponding to DNA extracted from approximately 23 cells of
      Alcaligenes faecalis. Meanwhile, PCR primers generated a detectable amount of the
      amplicon from 2.2*10(2) CFU/ml cell suspensions from the soil. Analysis of
      vegetable phylloepiphytic and farming soil microbes showed that bacterial species
      belonging to the genus Alcaligenes were present in the range from 0.9*10(0) CFU
      per gram (or cm(2)) (Japanese radish: Raphanus sativus var. longipinnatus) to
      more than 1.1*10(4) CFU/g (broccoli flowers: Brassica oleracea var. italic),
      while 2.4*10(2) to 4.4*10(3) CFU/g were detected from all soil samples. These
      results indicated that Alcaligenes species are present in the phytosphere at
      levels 10-1000 times lower than those in soil. Our approach may be useful for
      tracking or quantifying species of the genus Alcaligenes in the agricultural
      environment. 

PMID- 24670616
TI  - Pulsed-Field Gel Electrophoresis (PFGE) pattern analysis and chlorine-resistance
      of Legionella pneumophila isolated from hot spring water samples.
AB  - For a microbial ecological analysis, 20 strains of Legionella pneumophila
      isolated from both unchlorinated Noyu (unattended natural hot spring) samples and
      chlorinated hot spring bath water samples collected throughout Japan were
      subjected to a clustering analysis on the basis of a Pulsed-Field Gel
      Electrophoresis (PFGE) pattern analysis. The PFGE patterns obtained from 19
      strains of L. pneumophila after digestion with SfiI were used to divide the
      strains into two groups (Groups A and B), although the similarity level was very
      low among the groups. Group A consisted of 8 strains, and all of these strains
      were isolated from hot spring bath water samples. Group B consisted of 11
      strains, and all but two of these strains were isolated from Noyu samples. The
      chlorine resistance (99.9% CT values) of these isolates was experimentally
      confirmed, and we attempted to define the relationship between chlorine
      resistance and the geno-cluster. The average CT value of group A (8 strains from
      hot spring bath water) was 0.49 mg?min/l and the average of group B (9 strains
      from Noyu samples) was 0.29 mg?min/l. No remarkable differences in the CT values
      for the groups were found. A chlorine-sensitive Noyu strain (0.14 mg?min/l) and a
      chlorine-resistant strain (0.62 mg?min/l) from hot spring bath water were then
      compared to identify any differences in their lipid composition. There was no
      notable difference in the ratio of saturated to unsaturated fatty acids between
      the chlorine-sensitive and chlorine-resistant bacteria. However, the chlorine
      sensitive and chlorine-resistant bacteria demonstrated differences in the
      relative percentages of cell wall and cell membrane fatty acids.

PMID- 24670617
TI  - Validation study of a commercial aflatoxin detection kit according to the
      notification method in Japan.
AB  - A commercial aflatoxin detection ELISA kit, "RIDASCREEN((r)) FAST Aflatoxin", was
      validated with corn samples naturally contaminated with aflatoxin and non
      contaminated reference corn samples according to the Japanese Notification Method
      ShokuAnHatsu 0816-7. The trueness, intra-laboratory repeatability, intermediate
      precision, limit of detection and limit of quantitation were found to be 91%,
      10%, 6.4%, 0.6MUg/kg and 2MUg/kg, respectively, and the performance of the kit
      was recognized as complying with all criteria in the Supplement Table of the
      Notification. These data suggest that this kit is useful as a simplified device
      to screen out negative corn samples contaminated with less than 4MUg/kg. 

PMID- 24670618
TI  - Evaluation of a rapid oral bacteria quantification system using dielectrophoresis
      and the impedance measurement.
AB  - To clarify the availability of the dielectrophoretic impedance measurement
      (DEPIM) system as the evaluator for oral care, we evaluated the usefulness of
      DEPIM system by comparison with the standard plate counting (SPC) method. First,
      the relationship between the DEPIM results and bacterial concentration measured
      by SPC was clarified. Next, the measurement of the microorganism number in a
      mixed suspension was evaluated with DEPIM and SPC. The bacterial counts with
      DEPIM strongly correlated with those with SPC (r(2)=0.633-0.997) and this
      correlation was also shown in the measurement of a mixed bacterial suspension
      (ranging from 10(5) to 10(8) cfu/ml) of two bacterial species. Moreover, the
      experiments using dissociating enzymes to eliminate the influence of the size of
      the bacterial aggregates demonstrated that the microbial measurement results with
      DEPIM are unaffected by bacterial aggregates. This study demonstrated that
      bacterial counts with DEPIM strongly correlated with those with SPC and were
      unaffected by bacterial aggregates. 

PMID- 24670619
TI  - Evaluation of Mdh1 protein as an antigenic candidate for a vaccine against
      candidiasis.
AB  - Candida albicans malate dehydrogenase (Mdh1p) has been screened by previous
      proteome studies as a candidate for a vaccine against candidiasis. In this study,
      recombinant Mdh1 protein with a His-tag was produced in Escherichia coli and
      evaluated as an immunogenic protein against candidiasis. Mdh1p was administrated
      to mice by two methods subcutaneous injection and intranasal administration
      before challenging them with a lethal dose of C. albicans. After vaccination of
      Mdh1p, antibody responses were observed. To evaluate the vaccination effect of
      Mdh1p, survival tests were performed after 35 d. Although all control mice died
      within 24 d or 25 d, 100% and 80% of mice survived with subcutaneous and
      intranasal administration, respectively. Therefore, our results indicate that,
      among C. albicans antigens examined thus far, Mdh1p is currently the most
      effective antigen for use as a vaccine for C. albicans. 

PMID- 24670620
TI  - Rapid detection of microbes in the dialysis solution by the microcolony
      fluorescence staining method (Millflex quantum).
AB  - A chemiluminescence system, Milliflex Quantum (MFQ), to detect microcolonies, has
      been used in the pharmaceutical field. In this study, we investigated aquatic
      bacteria in hemodialysis solutions sampled from bioburden areas in 4 dialysis
      faculties. Using MFQ, microcolonies could be detected after a short incubation
      period. The colony count detected with MFQ after a 48-hour incubation was 92% +/-
      39%, compared to that after the conventionally used 7-14-day incubation period;
      in addition, the results also showed a linear correlation. Moreover, MFQ-based
      analysis allowed the visualization of damaged cells and of the high density due
      to the excessive amount of bacteria. These results suggested that MFQ had
      adequate sensitivity to detect microbacteria in dialysis solutions, and it was
      useful for validating the conditions of conventional culture methods.

PMID- 24670621
TI  - Addressing the global health security agenda.

PMID- 24670623
TI  - Advancing the portfolio of tuberculosis diagnostics, drugs, biomarkers, and
      vaccines.

PMID- 24670622
TI  - Single-tablet, once-daily treatment regimens for HIV.

PMID- 24670624
TI  - Drug-resistant Salmonella enterica serotype Kentucky in Europe.

PMID- 24670625
TI  - Clinical epidemiology of Klebsiella pneumoniae carbapenemases.

PMID- 24670626
TI  - Colorectal neoplasia associated with Streptococcus gallolyticus subspecies
      pasteurianus.

PMID- 24670627
TI  - New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and
      future prospects.
AB  - About 1.3 million people died of tuberculosis in 2012, despite availability of
      effective drug treatment. Barriers to improvements in outcomes include long
      treatment duration (resulting in poor patient adherence and loss of patients to
      follow-up), complex regimens that involve expensive and toxic drugs, toxic
      effects when given with antiretroviral therapy, and multidrug resistance. After
      50 years of no antituberculosis drug development, a promising pipeline is
      emerging through the repurposing of old drugs, re-engineering of existing
      antibacterial compounds, and discovery of new compounds. A range of novel
      antituberculosis drugs are in preclinical development, several phase 2 and 3
      trials are underway, and use of adjunct therapies is being explored for drug
      sensitive and drug-resistant tuberculosis. Historical advances include approval
      of two new drugs, delamanid and bedaquiline. Combinations of new and existing
      drugs are being assessed to shorten the duration of therapy and to treat
      multidrug-resistant tuberculosis. There has also been progress in development of
      new antituberculosis drugs that are active against dormant or persister
      populations of Mycobacterium tuberculosis. In this Review, we discuss recent
      advances in antituberculosis drug discovery and development, clinical trial
      designs, laboratory methods, and adjunct host-directed therapies, and we provide
      an update of phase 3 trials of various fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB,
      and REMoxTB). We also emphasise the need to engage the community in design,
      implementation, and uptake of research, to increase international cooperation
      between drug developers and health-care providers adopting new regimens. 

PMID- 24670628
TI  - A high-definition view of endogenous fungal endophthalmitis.

PMID- 24670631
TI  - Three-dimensional distribution of plastic pellets in sandy beaches: shifting
      paradigms.
AB  - Plastic pellets are worldwide contaminants that accumulate in the ocean,
      especially in sandy beaches, where their historic standing-stock quantification
      relies on surface sediment samples. We demonstrated these particles present a
      three-dimensional instead of a simple along-across shore distribution, being
      found as deep as 2.0 m, with surface layers accounting for <10% of the total
      abundance in the sediment column. This gradient seemed to be more related to
      oceanographic rather than anthropic processes, suggesting a general pattern whose
      applicability to microplastics and sedimentary environments as a whole should be
      investigated. This poses criticism in the exactness of standing-stock records and
      demands urgent discussion of sampling protocols.

PMID- 24670632
TI  - Consequences of a refuge for the predator-prey dynamics of a wolf-elk system in
      Banff National Park, Alberta, Canada.
AB  - Refugia can affect predator-prey dynamics via movements between refuge and non
      refuge areas. We examine the influence of a refuge on population dynamics in a
      large mammal predator-prey system. Wolves (Canis lupus) have recolonized much of
      their former range in North America, and as a result, ungulate prey have
      exploited refugia to reduce predation risk with unknown impacts on wolf-prey
      dynamics. We examined the influence of a refuge on elk (Cervus elaphus) and wolf
      population dynamics in Banff National Park. Elk occupy the Banff townsite with
      little predation, whereas elk in the adjoining Bow Valley experience higher wolf
      predation. The Banff refuge may influence Bow Valley predator-prey dynamics
      through source-sink movements. To test this hypothesis, we used 26 years of wolf
      and elk population counts and the Delayed Rejection Adaptive Metropolis Markov
      chain Monte Carlo method to fit five predator-prey models: 1) with no source-sink
      movements, 2) with elk density-dependent dispersal from the refuge to the non
      refuge, 3) with elk predation risk avoidance movements from the non-refuge to the
      refuge, 4) with differential movement rates between refuge and non-refuge, and 5)
      with short-term, source-sink wolf movements. Model 1 provided the best fit of the
      data, as measured by Akaike Information Criterion (AIC). In the top model, Banff
      and Bow Valley elk had median growth rates of 0.08 and 0.03 (95% credibility
      intervals [CIs]: 0.027-0.186 and 0.001-0.143), respectively, Banff had a median
      carrying capacity of 630 elk (95% CI: 471.9-2676.9), Bow Valley elk had a median
      wolf encounter rate of 0.02 (95% CI: 0.013-0.030), and wolves had a median death
      rate of 0.23 (95% CI: 0.146-0.335) and a median conversion efficiency of 0.07
      (95% CI: 0.031-0.124). We found little evidence for potential source-sink
      movements influencing the predator-prey dynamics of this system. This result
      suggests that the refuge was isolated from the non-refuge. 

PMID- 24670633
TI  - Commentary: The ARUBA trial.

PMID- 24670634
TI  - Metabolic determinants of cancer cell sensitivity to glucose limitation and
      biguanides.
AB  - As the concentrations of highly consumed nutrients, particularly glucose, are
      generally lower in tumours than in normal tissues, cancer cells must adapt their
      metabolism to the tumour microenvironment. A better understanding of these
      adaptations might reveal cancer cell liabilities that can be exploited for
      therapeutic benefit. Here we developed a continuous-flow culture apparatus
      (Nutrostat) for maintaining proliferating cells in low-nutrient media for long
      periods of time, and used it to undertake competitive proliferation assays on a
      pooled collection of barcoded cancer cell lines cultured in low-glucose
      conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA
      interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation
      (OXPHOS) as the major pathway required for optimal proliferation in low glucose.
      We found that cell lines most sensitive to low glucose are defective in the
      OXPHOS upregulation that is normally caused by glucose limitation as a result of
      either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose
      utilization. These defects predict sensitivity to biguanides, antidiabetic drugs
      that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour
      xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA
      mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone
      oxidoreductase that allows bypass of complex I function. Thus, we conclude that
      mtDNA mutations and impaired glucose utilization are potential biomarkers for
      identifying tumours with increased sensitivity to OXPHOS inhibitors. 

PMID- 24670635
TI  - Vascular biology: Brain vessels squeezed to death.

PMID- 24670636
TI  - FXR is a molecular target for the effects of vertical sleeve gastrectomy.
AB  - Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at
      present the most effective therapy for the treatment of obesity, and are
      associated with considerable improvements in co-morbidities, including type-2
      diabetes mellitus. The underlying molecular mechanisms contributing to these
      benefits remain largely undetermined, despite offering the potential to reveal
      new targets for therapeutic intervention. Substantial changes in circulating
      total bile acids are known to occur after VSG. Moreover, bile acids are known to
      regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor,
      also known as NR1H4). We therefore examined the results of VSG surgery applied to
      mice with diet-induced obesity and targeted genetic disruption of FXR. Here we
      demonstrate that the therapeutic value of VSG does not result from mechanical
      restriction imposed by a smaller stomach. Rather, VSG is associated with
      increased circulating bile acids, and associated changes to gut microbial
      communities. Moreover, in the absence of FXR, the ability of VSG to reduce body
      weight and improve glucose tolerance is substantially reduced. These results
      point to bile acids and FXR signalling as an important molecular underpinning for
      the beneficial effects of this weight-loss surgery. 

PMID- 24670637
TI  - Structure of the LH1-RC complex from Thermochromatium tepidum at 3.0 A.
AB  - The light-harvesting core antenna (LH1) and the reaction centre (RC) of purple
      photosynthetic bacteria form a supramolecular complex (LH1-RC) to use sunlight
      energy in a highly efficient manner. Here we report the first near-atomic
      structure, to our knowledge, of a LH1-RC complex, namely that of a Ca(2+)-bound
      complex from Thermochromatium tepidum, which reveals detailed information on the
      arrangement and interactions of the protein subunits and the cofactors. The RC is
      surrounded by 16 heterodimers of the LH1 alphabeta-subunit that form a completely
      closed structure. The Ca(2+) ions are located at the periplasmic side of LH1.
      Thirty-two bacteriochlorophyll and 16 spirilloxanthin molecules in the LH1 ring
      form an elliptical assembly. The geometries of the pigment assembly involved in
      the absorption characteristics of the bacteriochlorophyll in LH1 and excitation
      energy transfer among the pigments are reported. In addition, possible ubiquinone
      channels in the closed LH1 complex are proposed based on the atomic structure. 

PMID- 24670638
TI  - Dynamics of continental accretion.
AB  - Subduction zones become congested when they try to consume buoyant, exotic crust.
      The accretionary mountain belts (orogens) that form at these convergent plate
      margins have been the principal sites of lateral continental growth through
      Earth's history. Modern examples of accretionary margins are the North American
      Cordilleras and southwest Pacific subduction zones. The geologic record contains
      abundant accretionary orogens, such as the Tasmanides, along the eastern margin
      of the supercontinent Gondwana, and the Altaides, which formed on the southern
      margin of Laurasia. In modern and ancient examples of long-lived accretionary
      orogens, the overriding plate is subjected to episodes of crustal extension and
      back-arc basin development, often related to subduction rollback and transient
      episodes of orogenesis and crustal shortening, coincident with accretion of
      exotic crust. Here we present three-dimensional dynamic models that show how
      accretionary margins evolve from the initial collision, through a period of plate
      margin instability, to re-establishment of a stable convergent margin. The models
      illustrate how significant curvature of the orogenic system develops, as well as
      the mechanism for tectonic escape of the back-arc region. The complexity of the
      morphology and the evolution of the system are caused by lateral rollback of a
      tightly arcuate trench migrating parallel to the plate boundary and orthogonally
      to the convergence direction. We find geological and geophysical evidence for
      this process in the Tasmanides of eastern Australia, and infer that this is a
      recurrent and global phenomenon. 

PMID- 24670639
TI  - Diversity and dynamics of the Drosophila transcriptome.
AB  - Animal transcriptomes are dynamic, with each cell type, tissue and organ system
      expressing an ensemble of transcript isoforms that give rise to substantial
      diversity. Here we have identified new genes, transcripts and proteins using
      poly(A)+ RNA sequencing from Drosophila melanogaster in cultured cell lines,
      dissected organ systems and under environmental perturbations. We found that a
      small set of mostly neural-specific genes has the potential to encode thousands
      of transcripts each through extensive alternative promoter usage and RNA
      splicing. The magnitudes of splicing changes are larger between tissues than
      between developmental stages, and most sex-specific splicing is gonad-specific.
      Gonads express hundreds of previously unknown coding and long non-coding RNAs
      (lncRNAs), some of which are antisense to protein-coding genes and produce short
      regulatory RNAs. Furthermore, previously identified pervasive intergenic
      transcription occurs primarily within newly identified introns. The fly
      transcriptome is substantially more complex than previously recognized, with this
      complexity arising from combinatorial usage of promoters, splice sites and
      polyadenylation sites.

PMID- 24670640
TI  - Nectar secretion requires sucrose phosphate synthases and the sugar transporter
      SWEET9.
AB  - Angiosperms developed floral nectaries that reward pollinating insects. Although
      nectar function and composition have been characterized, the mechanism of nectar
      secretion has remained unclear. Here we identify SWEET9 as a nectary-specific
      sugar transporter in three eudicot species: Arabidopsis thaliana, Brassica rapa
      (extrastaminal nectaries) and Nicotiana attenuata (gynoecial nectaries). We show
      that SWEET9 is essential for nectar production and can function as an efflux
      transporter. We also show that sucrose phosphate synthase genes, encoding key
      enzymes for sucrose biosynthesis, are highly expressed in nectaries and that
      their expression is also essential for nectar secretion. Together these data are
      consistent with a model in which sucrose is synthesized in the nectary parenchyma
      and subsequently secreted into the extracellular space via SWEET9, where sucrose
      is hydrolysed by an apoplasmic invertase to produce a mixture of sucrose, glucose
      and fructose. The recruitment of SWEET9 for sucrose export may have been a key
      innovation, and could have coincided with the evolution of core eudicots and
      contributed to the evolution of nectar secretion to reward pollinators. 

PMID- 24670641
TI  - XBP1 promotes triple-negative breast cancer by controlling the HIF1alpha pathway.
AB  - Cancer cells induce a set of adaptive response pathways to survive in the face of
      stressors due to inadequate vascularization. One such adaptive pathway is the
      unfolded protein (UPR) or endoplasmic reticulum (ER) stress response mediated in
      part by the ER-localized transmembrane sensor IRE1 (ref. 2) and its substrate
      XBP1 (ref. 3). Previous studies report UPR activation in various human tumours,
      but the role of XBP1 in cancer progression in mammary epithelial cells is largely
      unknown. Triple-negative breast cancer (TNBC)--a form of breast cancer in which
      tumour cells do not express the genes for oestrogen receptor, progesterone
      receptor and HER2 (also called ERBB2 or NEU)--is a highly aggressive malignancy
      with limited treatment options. Here we report that XBP1 is activated in TNBC and
      has a pivotal role in the tumorigenicity and progression of this human breast
      cancer subtype. In breast cancer cell line models, depletion of XBP1 inhibited
      tumour growth and tumour relapse and reduced the CD44(high)CD24(low) population.
      Hypoxia-inducing factor 1alpha (HIF1alpha) is known to be hyperactivated in
      TNBCs. Genome-wide mapping of the XBP1 transcriptional regulatory network
      revealed that XBP1 drives TNBC tumorigenicity by assembling a transcriptional
      complex with HIF1alpha that regulates the expression of HIF1alpha targets via the
      recruitment of RNA polymerase II. Analysis of independent cohorts of patients
      with TNBC revealed a specific XBP1 gene expression signature that was highly
      correlated with HIF1alpha and hypoxia-driven signatures and that strongly
      associated with poor prognosis. Our findings reveal a key function for the XBP1
      branch of the UPR in TNBC and indicate that targeting this pathway may offer
      alternative treatment strategies for this aggressive subtype of breast cancer.

PMID- 24670642
TI  - Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma.
AB  - Treatment of BRAF(V600E) mutant melanoma by small molecule drugs that target the
      BRAF or MEK kinases can be effective, but resistance develops invariably. In
      contrast, colon cancers that harbour the same BRAF(V600E) mutation are
      intrinsically resistant to BRAF inhibitors, due to feedback activation of the
      epidermal growth factor receptor (EGFR). Here we show that 6 out of 16 melanoma
      tumours analysed acquired EGFR expression after the development of resistance to
      BRAF or MEK inhibitors. Using a chromatin-regulator-focused short hairpin RNA
      (shRNA) library, we find that suppression of sex determining region Y-box 10
      (SOX10) in melanoma causes activation of TGF-beta signalling, thus leading to
      upregulation of EGFR and platelet-derived growth factor receptor-beta (PDGFRB),
      which confer resistance to BRAF and MEK inhibitors. Expression of EGFR in
      melanoma or treatment with TGF-beta results in a slow-growth phenotype with cells
      displaying hallmarks of oncogene-induced senescence. However, EGFR expression or
      exposure to TGF-beta becomes beneficial for proliferation in the presence of BRAF
      or MEK inhibitors. In a heterogeneous population of melanoma cells having varying
      levels of SOX10 suppression, cells with low SOX10 and consequently high EGFR
      expression are rapidly enriched in the presence of drug, but this is reversed
      when the drug treatment is discontinued. We find evidence for SOX10 loss and/or
      activation of TGF-beta signalling in 4 of the 6 EGFR-positive drug-resistant
      melanoma patient samples. Our findings provide a rationale for why some BRAF or
      MEK inhibitor-resistant melanoma patients may regain sensitivity to these drugs
      after a 'drug holiday' and identify patients with EGFR-positive melanoma as a
      group that may benefit from re-treatment after a drug holiday. 

PMID- 24670643
TI  - Constitutional and somatic rearrangement of chromosome 21 in acute lymphoblastic
      leukaemia.
AB  - Changes in gene dosage are a major driver of cancer, known to be caused by a
      finite, but increasingly well annotated, repertoire of mutational mechanisms.
      This can potentially generate correlated copy-number alterations across hundreds
      of linked genes, as exemplified by the 2% of childhood acute lymphoblastic
      leukaemia (ALL) with recurrent amplification of megabase regions of chromosome 21
      (iAMP21). We used genomic, cytogenetic and transcriptional analysis, coupled with
      novel bioinformatic approaches, to reconstruct the evolution of iAMP21 ALL. Here
      we show that individuals born with the rare constitutional Robertsonian
      translocation between chromosomes 15 and 21, rob(15;21)(q10;q10)c, have
      approximately 2,700-fold increased risk of developing iAMP21 ALL compared to the
      general population. In such cases, amplification is initiated by a chromothripsis
      event involving both sister chromatids of the Robertsonian chromosome, a novel
      mechanism for cancer predisposition. In sporadic iAMP21, breakage-fusion-bridge
      cycles are typically the initiating event, often followed by chromothripsis. In
      both sporadic and rob(15;21)c-associated iAMP21, the final stages frequently
      involve duplications of the entire abnormal chromosome. The end-product is a
      derivative of chromosome 21 or the rob(15;21)c chromosome with gene dosage
      optimized for leukaemic potential, showing constrained copy-number levels over
      multiple linked genes. Thus, dicentric chromosomes may be an important
      precipitant of chromothripsis, as we show rob(15;21)c to be constitutionally
      dicentric and breakage-fusion-bridge cycles generate dicentric chromosomes
      somatically. Furthermore, our data illustrate that several cancer-specific
      mutational processes, applied sequentially, can coordinate to fashion copy-number
      profiles over large genomic scales, incrementally refining the fitness benefits
      of aggregated gene dosage changes. 

PMID- 24670644
TI  - A ring system detected around the Centaur (10199) Chariklo.
AB  - Hitherto, rings have been found exclusively around the four giant planets in the
      Solar System. Rings are natural laboratories in which to study dynamical
      processes analogous to those that take place during the formation of planetary
      systems and galaxies. Their presence also tells us about the origin and evolution
      of the body they encircle. Here we report observations of a multichord stellar
      occultation that revealed the presence of a ring system around (10199) Chariklo,
      which is a Centaur--that is, one of a class of small objects orbiting primarily
      between Jupiter and Neptune--with an equivalent radius of 124 +/-  9 kilometres
      (ref. 2). There are two dense rings, with respective widths of about 7 and 3
      kilometres, optical depths of 0.4 and 0.06, and orbital radii of 391 and 405
      kilometres. The present orientation of the ring is consistent with an edge-on
      geometry in 2008, which provides a simple explanation for the dimming of the
      Chariklo system between 1997 and 2008, and for the gradual disappearance of ice
      and other absorption features in its spectrum over the same period. This implies
      that the rings are partly composed of water ice. They may be the remnants of a
      debris disk, possibly confined by embedded, kilometre-sized satellites.

PMID- 24670645
TI  - Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington's
      disease.
AB  - Huntington's disease is an autosomal dominant disease associated with a mutation
      in the gene encoding huntingtin (Htt) leading to expanded polyglutamine repeats
      of mutant Htt (mHtt) that elicit oxidative stress, neurotoxicity, and motor and
      behavioural changes. Huntington's disease is characterized by highly selective
      and profound damage to the corpus striatum, which regulates motor function.
      Striatal selectivity of Huntington's disease may reflect the striatally selective
      small G protein Rhes binding to mHtt and enhancing its neurotoxicity. Specific
      molecular mechanisms by which mHtt elicits neurodegeneration have been hard to
      determine. Here we show a major depletion of cystathionine gamma-lyase (CSE), the
      biosynthetic enzyme for cysteine, in Huntington's disease tissues, which may
      mediate Huntington's disease pathophysiology. The defect occurs at the
      transcriptional level and seems to reflect influences of mHtt on specificity
      protein 1, a transcriptional activator for CSE. Consistent with the notion of
      loss of CSE as a pathogenic mechanism, supplementation with cysteine reverses
      abnormalities in cultures of Huntington's disease tissues and in intact mouse
      models of Huntington's disease, suggesting therapeutic potential. 

PMID- 24670646
TI  - Solar system: Ring in the new.

PMID- 24670647
TI  - Capillary pericytes regulate cerebral blood flow in health and disease.
AB  - Increases in brain blood flow, evoked by neuronal activity, power neural
      computation and form the basis of BOLD (blood-oxygen-level-dependent) functional
      imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or
      also by capillary pericytes, is controversial. We demonstrate that neuronal
      activity and the neurotransmitter glutamate evoke the release of messengers that
      dilate capillaries by actively relaxing pericytes. Dilation is mediated by
      prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting
      20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries
      dilate before arterioles and are estimated to produce 84% of the blood flow
      increase. In pathology, ischaemia evokes capillary constriction by pericytes. We
      show that this is followed by pericyte death in rigor, which may irreversibly
      constrict capillaries and damage the blood-brain barrier. Thus, pericytes are
      major regulators of cerebral blood flow and initiators of functional imaging
      signals. Prevention of pericyte constriction and death may reduce the long
      lasting blood flow decrease that damages neurons after stroke. 

PMID- 24670648
TI  - Maternal retinoids control type 3 innate lymphoid cells and set the offspring
      immunity.
AB  - The impact of nutritional status during fetal life on the overall health of
      adults has been recognized; however, dietary effects on the developing immune
      system are largely unknown. Development of secondary lymphoid organs occurs
      during embryogenesis and is considered to be developmentally programmed.
      Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid
      cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse
      fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in
      utero, which pre-sets the immune fitness in adulthood. We found that embryonic
      lymphoid organs contain ILC progenitors that differentiate locally into mature
      LTi cells. Local LTi cell differentiation was controlled by maternal retinoid
      intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner.
      RA controlled LTi cell maturation upstream of the transcription factor RORgammat.
      Accordingly, enforced expression of Rorgt restored maturation of LTi cells with
      impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus.
      Finally, we established that maternal levels of dietary retinoids control the
      size of secondary lymphoid organs and the efficiency of immune responses in the
      adult offspring. Our results reveal a molecular link between maternal nutrients
      and the formation of immune structures required for resistance to infection in
      the offspring. 

PMID- 24670649
TI  - Herbivores and nutrients control grassland plant diversity via light limitation.
AB  - Human alterations to nutrient cycles and herbivore communities are affecting
      global biodiversity dramatically. Ecological theory predicts these changes should
      be strongly counteractive: nutrient addition drives plant species loss through
      intensified competition for light, whereas herbivores prevent competitive
      exclusion by increasing ground-level light, particularly in productive systems.
      Here we use experimental data spanning a globally relevant range of conditions to
      test the hypothesis that herbaceous plant species losses caused by eutrophication
      may be offset by increased light availability due to herbivory. This experiment,
      replicated in 40 grasslands on 6 continents, demonstrates that nutrients and
      herbivores can serve as counteracting forces to control local plant diversity
      through light limitation, independent of site productivity, soil nitrogen,
      herbivore type and climate. Nutrient addition consistently reduced local
      diversity through light limitation, and herbivory rescued diversity at sites
      where it alleviated light limitation. Thus, species loss from anthropogenic
      eutrophication can be ameliorated in grasslands where herbivory increases ground
      level light. 

PMID- 24670650
TI  - Structure of the human P2Y12 receptor in complex with an antithrombotic drug.
AB  - P2Y receptors (P2YRs), a family of purinergic G-protein-coupled receptors
      (GPCRs), are activated by extracellular nucleotides. There are a total of eight
      distinct functional P2YRs expressed in human, which are subdivided into P2Y1-like
      receptors and P2Y12-like receptors. Their ligands are generally charged molecules
      with relatively low bioavailability and stability in vivo, which limits our
      understanding of this receptor family. P2Y12R regulates platelet activation and
      thrombus formation, and several antithrombotic drugs targeting P2Y12R--including
      the prodrugs clopidogrel (Plavix) and prasugrel (Effient) that are metabolized
      and bind covalently, and the nucleoside analogue ticagrelor (Brilinta) that acts
      directly on the receptor--have been approved for the prevention of stroke and
      myocardial infarction. However, limitations of these drugs (for example, a very
      long half-life of clopidogrel action and a characteristic adverse effect profile
      of ticagrelor) suggest that there is an unfulfilled medical need for developing a
      new generation of P2Y12R inhibitors. Here we report the 2.6 A resolution crystal
      structure of human P2Y12R in complex with a non-nucleotide reversible antagonist,
      AZD1283. The structure reveals a distinct straight conformation of helix V, which
      sets P2Y12R apart from all other known class A GPCR structures. With AZD1283
      bound, the highly conserved disulphide bridge in GPCRs between helix III and
      extracellular loop 2 is not observed and appears to be dynamic. Along with the
      details of the AZD1283-binding site, analysis of the extracellular interface
      reveals an adjacent ligand-binding region and suggests that both pockets could be
      required for dinucleotide binding. The structure provides essential insights for
      the development of improved P2Y12R ligands and allosteric modulators as drug
      candidates.

PMID- 24670652
TI  - Nuclear reprogramming by interphase cytoplasm of two-cell mouse embryos.
AB  - Successful mammalian cloning using somatic cell nuclear transfer (SCNT) into
      unfertilized, metaphase II (MII)-arrested oocytes attests to the cytoplasmic
      presence of reprogramming factors capable of inducing totipotency in somatic cell
      nuclei. However, these poorly defined maternal factors presumably decline sharply
      after fertilization, as the cytoplasm of pronuclear-stage zygotes is reportedly
      inactive. Recent evidence suggests that zygotic cytoplasm, if maintained at
      metaphase, can also support derivation of embryonic stem (ES) cells after SCNT,
      albeit at low efficiency. This led to the conclusion that critical oocyte
      reprogramming factors present in the metaphase but not in the interphase
      cytoplasm are 'trapped' inside the nucleus during interphase and effectively
      removed during enucleation. Here we investigated the presence of reprogramming
      activity in the cytoplasm of interphase two-cell mouse embryos (I2C). First, the
      presence of candidate reprogramming factors was documented in both intact and
      enucleated metaphase and interphase zygotes and two-cell embryos. Consequently,
      enucleation did not provide a likely explanation for the inability of interphase
      cytoplasm to induce reprogramming. Second, when we carefully synchronized the
      cell cycle stage between the transplanted nucleus (ES cell, fetal fibroblast or
      terminally differentiated cumulus cell) and the recipient I2C cytoplasm, the
      reconstructed SCNT embryos developed into blastocysts and ES cells capable of
      contributing to traditional germline and tetraploid chimaeras. Last, direct
      transfer of cloned embryos, reconstructed with ES cell nuclei, into recipients
      resulted in live offspring. Thus, the cytoplasm of I2C supports efficient
      reprogramming, with cell cycle synchronization between the donor nucleus and
      recipient cytoplasm as the most critical parameter determining success. The
      ability to use interphase cytoplasm in SCNT could aid efforts to generate
      autologous human ES cells for regenerative applications, as donated or discarded
      embryos are more accessible than unfertilized MII oocytes. 

PMID- 24670651
TI  - Identification of genomic alterations in oesophageal squamous cell cancer.
AB  - Oesophageal cancer is one of the most aggressive cancers and is the sixth leading
      cause of cancer death worldwide. Approximately 70% of global oesophageal cancer
      cases occur in China, with oesophageal squamous cell carcinoma (ESCC) being the
      histopathological form in the vast majority of cases (>90%). Currently, there are
      limited clinical approaches for the early diagnosis and treatment of ESCC,
      resulting in a 10% five-year survival rate for patients. However, the full
      repertoire of genomic events leading to the pathogenesis of ESCC remains unclear.
      Here we describe a comprehensive genomic analysis of 158 ESCC cases, as part of
      the International Cancer Genome Consortium research project. We conducted whole
      genome sequencing in 17 ESCC cases and whole-exome sequencing in 71 cases, of
      which 53 cases, plus an additional 70 ESCC cases not used in the whole-genome and
      whole-exome sequencing, were subjected to array comparative genomic hybridization
      analysis. We identified eight significantly mutated genes, of which six are well
      known tumour-associated genes (TP53, RB1, CDKN2A, PIK3CA, NOTCH1, NFE2L2), and
      two have not previously been described in ESCC (ADAM29 and FAM135B). Notably,
      FAM135B is identified as a novel cancer-implicated gene as assayed for its
      ability to promote malignancy of ESCC cells. Additionally, MIR548K, a microRNA
      encoded in the amplified 11q13.3-13.4 region, is characterized as a novel
      oncogene, and functional assays demonstrate that MIR548K enhances malignant
      phenotypes of ESCC cells. Moreover, we have found that several important histone
      regulator genes (MLL2 (also called KMT2D), ASH1L, MLL3 (KMT2C), SETD1B, CREBBP
      and EP300) are frequently altered in ESCC. Pathway assessment reveals that
      somatic aberrations are mainly involved in the Wnt, cell cycle and Notch
      pathways. Genomic analyses suggest that ESCC and head and neck squamous cell
      carcinoma share some common pathogenic mechanisms, and ESCC development is
      associated with alcohol drinking. This study has explored novel biological
      markers and tumorigenic pathways that would greatly improve therapeutic
      strategies for ESCC. 

PMID- 24670653
TI  - Structural biology: The purple heart of photosynthesis.

PMID- 24670655
TI  - Immunology: A is for immunity.

PMID- 24670654
TI  - Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl
      terminus.
AB  - Akt, also known as protein kinase B, plays key roles in cell proliferation,
      survival and metabolism. Akt hyperactivation contributes to many
      pathophysiological conditions, including human cancers, and is closely associated
      with poor prognosis and chemo- or radiotherapeutic resistance. Phosphorylation of
      Akt at S473 (ref. 5) and T308 (ref. 6) activates Akt. However, it remains unclear
      whether further mechanisms account for full Akt activation, and whether Akt
      hyperactivation is linked to misregulated cell cycle progression, another cancer
      hallmark. Here we report that Akt activity fluctuates across the cell cycle,
      mirroring cyclin A expression. Mechanistically, phosphorylation of S477 and T479
      at the Akt extreme carboxy terminus by cyclin-dependent kinase 2 (Cdk2)/cyclin A
      or mTORC2, under distinct physiological conditions, promotes Akt activation
      through facilitating, or functionally compensating for, S473 phosphorylation.
      Furthermore, deletion of the cyclin A2 allele in the mouse olfactory bulb leads
      to reduced S477/T479 phosphorylation and elevated cellular apoptosis. Notably,
      cyclin A2-deletion-induced cellular apoptosis in mouse embryonic stem cells is
      partly rescued by S477D/T479E-Akt1, supporting a physiological role for cyclin A2
      in governing Akt activation. Together, the results of our study show Akt
      S477/T479 phosphorylation to be an essential layer of the Akt activation
      mechanism to regulate its physiological functions, thereby providing a new
      mechanistic link between aberrant cell cycle progression and Akt hyperactivation
      in cancer. 

PMID- 24670656
TI  - Coherent control of the waveforms of recoilless gamma-ray photons.
AB  - The concepts and ideas of coherent, nonlinear and quantum optics have been
      extended to photon energies in the range of 10-100 kiloelectronvolts,
      corresponding to soft gamma-ray radiation (the term used when the radiation is
      produced in nuclear transitions) or, equivalently, hard X-ray radiation (the term
      used when the radiation is produced by electron motion). The recent experimental
      achievements in this energy range include the demonstration of parametric down
      conversion in the Langevin regime, electromagnetically induced transparency in a
      cavity, the collective Lamb shift, vacuum-assisted generation of atomic
      coherences and single-photon revival in nuclear absorbing multilayer structures.
      Also, realization of single-photon coherent storage and stimulated Raman
      adiabatic passage were recently proposed in this regime. More related work is
      discussed in a recent review. However, the number of tools for the coherent
      manipulation of interactions between gamma-ray photons and nuclear ensembles
      remains limited. Here we suggest and implement an efficient method to control the
      waveforms of gamma-ray photons coherently. In particular, we demonstrate the
      conversion of individual recoilless gamma-ray photons into a coherent, ultrashort
      pulse train and into a double pulse. Our method is based on the resonant
      interaction of gamma-ray photons with an ensemble of nuclei with a resonant
      transition frequency that is periodically modulated in time. The frequency
      modulation, which is achieved by a uniform vibration of the resonant absorber,
      owing to the Doppler effect, renders resonant absorption and dispersion both time
      dependent, allowing us to shape the waveforms of the incident gamma-ray photons.
      We expect that this technique will lead to advances in the emerging fields of
      coherent and quantum gamma-ray photon optics, providing a basis for the
      realization of gamma-ray-photon/nuclear-ensemble interfaces and quantum
      interference effects at nuclear gamma-ray transitions. 

PMID- 24670658
TI  - Structure of a type IV secretion system.
AB  - Bacterial type IV secretion systems translocate virulence factors into eukaryotic
      cells, distribute genetic material between bacteria and have shown potential as a
      tool for the genetic modification of human cells. Given the complex choreography
      of the substrate through the secretion apparatus, the molecular mechanism of the
      type IV secretion system has proved difficult to dissect in the absence of
      structural data for the entire machinery. Here we use electron microscopy to
      reconstruct the type IV secretion system encoded by the Escherichia coli R388
      conjugative plasmid. We show that eight proteins assemble in an intricate
      stoichiometric relationship to form an approximately 3 megadalton nanomachine
      that spans the entire cell envelope. The structure comprises an outer membrane
      associated core complex connected by a central stalk to a substantial inner
      membrane complex that is dominated by a battery of 12 VirB4 ATPase subunits
      organized as side-by-side hexameric barrels. Our results show a secretion system
      with markedly different architecture, and consequently mechanism, to other known
      bacterial secretion systems. 

PMID- 24670657
TI  - Disruption of Mediator rescues the stunted growth of a lignin-deficient
      Arabidopsis mutant.
AB  - Lignin is a phenylpropanoid-derived heteropolymer important for the strength and
      rigidity of the plant secondary cell wall. Genetic disruption of lignin
      biosynthesis has been proposed as a means to improve forage and bioenergy crops,
      but frequently results in stunted growth and developmental abnormalities, the
      mechanisms of which are poorly understood. Here we show that the phenotype of a
      lignin-deficient Arabidopsis mutant is dependent on the transcriptional co
      regulatory complex, Mediator. Disruption of the Mediator complex subunits MED5a
      (also known as REF4) and MED5b (also known as RFR1) rescues the stunted growth,
      lignin deficiency and widespread changes in gene expression seen in the
      phenylpropanoid pathway mutant ref8, without restoring the synthesis of guaiacyl
      and syringyl lignin subunits. Cell walls of rescued med5a/5b ref8 plants instead
      contain a novel lignin consisting almost exclusively of p-hydroxyphenyl lignin
      subunits, and moreover exhibit substantially facilitated polysaccharide
      saccharification. These results demonstrate that guaiacyl and syringyl lignin
      subunits are largely dispensable for normal growth and development, implicate
      Mediator in an active transcriptional process responsible for dwarfing and
      inhibition of lignin biosynthesis, and suggest that the transcription machinery
      and signalling pathways responding to cell wall defects may be important targets
      to include in efforts to reduce biomass recalcitrance. 

PMID- 24670659
TI  - A new fossil species supports an early origin for toothed whale echolocation.
AB  - Odontocetes (toothed whales, dolphins and porpoises) hunt and navigate through
      dark and turbid aquatic environments using echolocation; a key adaptation that
      relies on the same principles as sonar. Among echolocating vertebrates,
      odontocetes are unique in producing high-frequency vocalizations at the phonic
      lips, a constriction in the nasal passages just beneath the blowhole, and then
      using air sinuses and the melon to modulate their transmission. All extant
      odontocetes seem to echolocate; however, exactly when and how this complex
      behaviour--and its underlying anatomy--evolved is largely unknown. Here we report
      an odontocete fossil, Oligocene in age (approximately 28 Myr ago), from South
      Carolina (Cotylocara macei, gen. et sp. nov.) that has several features
      suggestive of echolocation: a dense, thick and downturned rostrum; air sac
      fossae; cranial asymmetry; and exceptionally broad maxillae. Our phylogenetic
      analysis places Cotylocara in a basal clade of odontocetes, leading us to infer
      that a rudimentary form of echolocation evolved in the early Oligocene, shortly
      after odontocetes diverged from the ancestors of filter-feeding whales
      (mysticetes). This was followed by enlargement of the facial muscles that
      modulate echolocation calls, which in turn led to marked, convergent changes in
      skull shape in the ancestors of Cotylocara, and in the lineage leading to extant
      odontocetes.

PMID- 24670660
TI  - Retraction: CLASP-mediated cortical microtubule organization guides PIN
      polarization axis.

PMID- 24670662
TI  - Efficient rotational cooling of Coulomb-crystallized molecular ions by a helium
      buffer gas.
AB  - The preparation of cold molecules is of great importance in many contexts, such
      as fundamental physics investigations, high-resolution spectroscopy of complex
      molecules, cold chemistry and astrochemistry. One versatile and widely applied
      method to cool molecules is helium buffer-gas cooling in either a supersonic beam
      expansion or a cryogenic trap environment. Another more recent method applicable
      to trapped molecular ions relies on sympathetic translational cooling, through
      collisional interactions with co-trapped, laser-cooled atomic ions, into
      spatially ordered structures called Coulomb crystals, combined with laser
      controlled internal-state preparation. Here we present experimental results on
      helium buffer-gas cooling of the rotational degrees of freedom of MgH(+)
      molecular ions, which have been trapped and sympathetically cooled in a cryogenic
      linear radio-frequency quadrupole trap. With helium collision rates of only about
      ten per second--that is, four to five orders of magnitude lower than in typical
      buffer-gas cooling settings--we have cooled a single molecular ion to a
      rotational temperature of 7.5(+0.9)(-0.7) kelvin, the lowest such temperature so
      far measured. In addition, by varying the shape of, or the number of atomic and
      molecular ions in, larger Coulomb crystals, or both, we have tuned the effective
      rotational temperature from about 7 kelvin to about 60 kelvin by changing the
      translational micromotion energy of the ions. The extremely low helium collision
      rate may allow for sympathetic sideband cooling of single molecular ions, and
      eventually make quantum-logic spectroscopy of buffer-gas-cooled molecular ions
      feasible. Furthermore, application of the present cooling scheme to complex
      molecular ions should enable single- or few-state manipulations of individual
      molecules of biological interest.

PMID- 24670661
TI  - Inhibition of miR-25 improves cardiac contractility in the failing heart.
AB  - Heart failure is characterized by a debilitating decline in cardiac function, and
      recent clinical trial results indicate that improving the contractility of heart
      muscle cells by boosting intracellular calcium handling might be an effective
      therapy. MicroRNAs (miRNAs) are dysregulated in heart failure but whether they
      control contractility or constitute therapeutic targets remains speculative.
      Using high-throughput functional screening of the human microRNAome, here we
      identify miRNAs that suppress intracellular calcium handling in heart muscle by
      interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake
      pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently
      delayed calcium uptake kinetics in cardiomyocytes in vitro and was upregulated in
      heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)
      mediated overexpression of miR-25 in vivo resulted in a significant loss of
      contractile function, injection of an antisense oligonucleotide (antagomiR)
      against miR-25 markedly halted established heart failure in a mouse model,
      improving cardiac function and survival relative to a control antagomiR
      oligonucleotide. These data reveal that increased expression of endogenous miR-25
      contributes to declining cardiac function during heart failure and suggest that
      it might be targeted therapeutically to restore function. 

PMID- 24670663
TI  - miRNAs trigger widespread epigenetically activated siRNAs from transposons in
      Arabidopsis.
AB  - In plants, post-transcriptional gene silencing (PTGS) is mediated by DICER-LIKE 1
      (DCL1)-dependent microRNAs (miRNAs), which also trigger 21-nucleotide secondary
      short interfering RNAs (siRNAs) via RNA-DEPENDENT RNA POLYMERASE 6 (RDR6), DCL4
      and ARGONAUTE 1 (AGO1), whereas transcriptional gene silencing (TGS) of
      transposons is mediated by 24-nucleotide heterochromatic (het)siRNAs, RDR2, DCL3
      and AGO4 (ref. 4). Transposons can also give rise to abundant 21-nucleotide
      'epigenetically activated' small interfering RNAs (easiRNAs) in DECREASED DNA
      METHYLATION 1 (ddm1) and DNA METHYLTRANSFERASE 1 (met1) mutants, as well as in
      the vegetative nucleus of pollen grains and in dedifferentiated plant cell
      cultures. Here we show that easiRNAs in Arabidopsis thaliana resemble secondary
      siRNAs, in that thousands of transposon transcripts are specifically targeted by
      more than 50 miRNAs for cleavage and processing by RDR6. Loss of RDR6, DCL4 or
      DCL1 in a ddm1 background results in loss of 21-nucleotide easiRNAs and severe
      infertility, but 24-nucleotide hetsiRNAs are partially restored, supporting an
      antagonistic relationship between PTGS and TGS. Thus miRNA-directed easiRNA
      biogenesis is a latent mechanism that specifically targets transposon
      transcripts, but only when they are epigenetically reactivated during
      reprogramming of the germ line. This ancient recognition mechanism may have been
      retained both by transposons to evade long-term heterochromatic silencing and by
      their hosts for genome defence. 

PMID- 24670664
TI  - Structural basis for translocation by AddAB helicase-nuclease and its arrest at
      chi sites.
AB  - In bacterial cells, processing of double-stranded DNA breaks for repair by
      homologous recombination is dependent upon the recombination hotspot sequence chi
      (Chi) and is catalysed by either an AddAB- or RecBCD-type helicase-nuclease
      (reviewed in refs 3, 4). These enzyme complexes unwind and digest the DNA duplex
      from the broken end until they encounter a chi sequence, whereupon they produce a
      3' single-stranded DNA tail onto which they initiate loading of the RecA protein.
      Consequently, regulation of the AddAB/RecBCD complex by chi is a key control
      point in DNA repair and other processes involving genetic recombination. Here we
      report crystal structures of Bacillus subtilis AddAB in complex with different
      chi-containing DNA substrates either with or without a non-hydrolysable ATP
      analogue. Comparison of these structures suggests a mechanism for DNA
      translocation and unwinding, suggests how the enzyme binds specifically to chi
      sequences, and explains how chi recognition leads to the arrest of AddAB (and
      RecBCD) translocation that is observed in single-molecule experiments. 

PMID- 24670665
TI  - Haematopoietic stem cells require a highly regulated protein synthesis rate.
AB  - Many aspects of cellular physiology remain unstudied in somatic stem cells, for
      example, there are almost no data on protein synthesis in any somatic stem cell.
      Here we set out to compare protein synthesis in haematopoietic stem cells (HSCs)
      and restricted haematopoietic progenitors. We found that the amount of protein
      synthesized per hour in HSCs in vivo was lower than in most other haematopoietic
      cells, even if we controlled for differences in cell cycle status or forced HSCs
      to undergo self-renewing divisions. Reduced ribosome function in Rpl24(Bst/+)
      mice further reduced protein synthesis in HSCs and impaired HSC function. Pten
      deletion increased protein synthesis in HSCs but also reduced HSC function.
      Rpl24(Bst/+) cell-autonomously rescued the effects of Pten deletion in HSCs;
      blocking the increase in protein synthesis, restoring HSC function, and delaying
      leukaemogenesis. Pten deficiency thus depletes HSCs and promotes leukaemia partly
      by increasing protein synthesis. Either increased or decreased protein synthesis
      impairs HSC function. 

PMID- 24670666
TI  - "Specificity Determinants" Improve Therapeutic Indices of Two Antimicrobial
      Peptides Piscidin 1 and Dermaseptin S4 Against the Gram-negative Pathogens
      Acinetobacter baumannii and Pseudomonas aeruginosa.
AB  - A new class of antimicrobial agents with lower rates of resistance and different
      targets is urgently needed because of the rapidly increasing resistance to
      classical antibiotics. Amphipathic cationic alpha-helical antimicrobial peptides
      (AMPs) represent such a class of compounds. In our previous studies, using a 26
      residue de novo designed antimicrobial peptide, we proposed the concept of
      "specificity determinant(s)": positively charged residue(s) in the center of the
      non-polar face of AMPs that could decrease hemolytic activity/toxicity but
      increase or maintain the same level of antimicrobial activity to increase
      dramatically the therapeutic index. In the current study, we used d-enantiomers
      of two AMPs, Piscidin 1 isolated from fish and dermaseptin S4 isolated from frog.
      We substituted different positions in the center of the hydrophobic face with one
      or two lysine residue(s) (one or two "specificity determinant(s)"). This simple
      modification not only maintained or improved antimicrobial activity against Gram
      negative pathogens Acinetobacter baumannii (11 strains) and Pseudomonas
      aeruginosa (6 strains), but also dramatically decreased hemolytic activity of
      human red blood cells, as predicted. Therapeutic indices improved by 55-fold and
      730-fold for piscidin 1 (I9K) and dermaseptin S4 (L7K, A14K), respectively,
      against A. baumannii. Similarly, the therapeutic indices improved 32-fold and 980
      fold for piscidin 1 (I9K) and dermaseptin S4 (L7K, A14K), respectively, against
      P. aeruginosa. 

PMID- 24670669
TI  - Broadband and crack-free antireflection coatings by self-assembled moth eye
      patterns.
AB  - We report broadband and quasi-omnidirectional antireflective (AR) structures
      inspired to the nipple arrays of moth eyes. These nanocoatings, based on thin
      elastomeric films, are prepared by simple self-assembly processing of a co
      polymer specifically designed to this purpose, and PDMS replica molding.
      Typically, their surface is covered by a compact distribution of hemispherical
      nanodomes of about 250 nm in diameter and about 100 nm in height. When these
      novel nanostructures are applied on a single glass surface, a maximum of 2%
      transmission enhancement (equivalent to a 50% reduction of the reflected
      component) towards wavelengths ranging from visible to near IR region is
      obtained. A considerable AR power is observed also at a wide range of incident
      angles ranging from normal to 50 degrees . These properties could be attributed
      to an optimized graded refractive index profile resulting from the randomly
      distributed and close-packed nanodomes. Moreover, thanks to their elastomeric
      nature, these crack-free films can be easily applied on glass, as stickers, and
      periodically replaced, thus offering the possibility of easy dirt removal from an
      optical device. 

PMID- 24670668
TI  - Expression of adrenoceptor subtypes in preterm piglet heart is different to term
      heart.
AB  - Preterm delivery increases the risk of inadequate systemic blood flow and
      hypotension, and many preterm infants fail to respond to conventional inotrope
      treatments. If the profile of cardiac adrenoceptor subtypes in the preterm
      neonate is different to that at term this may contribute to these clinical
      problems. This study measured mRNA expression of beta1, beta2, alpha1A, alpha2A
      and alpha2B-adrenoceptor subtypes by real time PCR in term (113d), preterm (91d)
      and preterm piglets (91d) exposed to maternal glucocorticoid treatment. Abundance
      of beta-adrenoceptor binding sites in the left ventricle was measured using
      saturation binding assays. Relative abundance of beta1-adrenoceptor mRNA in
      untreated preterm hearts was ~50% of term abundance in both left and right
      ventricles (P<0.001). Trends in receptor binding site density measurements
      supported this observation (P = 0.07). Glucocorticoid exposure increased beta1
      adrenoceptor mRNA levels in the right ventricle of preterm hearts (P = 0.008) but
      did not alter expression in the left ventricle (P>0.1). Relative abundance of
      alpha1A-adrenoceptor mRNA was the same in preterm and term piglet hearts (P =
      >0.1) but was reduced by maternal glucocorticoid treatment (P<0.01); alpha2A
      adrenoceptor mRNA abundance was higher in untreated and glucocorticoid exposed
      preterm piglet hearts than in term piglets (P<0.001). There was no difference
      between male and female piglets in mRNA abundance of any of the genes studied. In
      conclusion, there is reduced mRNA abundance of beta1-adrenoceptors in the preterm
      pig heart. If this lower expression of beta-adrenoceptors occurs in human preterm
      infants, it could explain their poor cardiovascular function and their frequent
      failure to respond to commonly used inotropes. 

PMID- 24670670
TI  - Redirecting the treatment and monitoring of organ transplant patients.

PMID- 24670671
TI  - Current world literature. Infection.

PMID- 24670673
TI  - Uterine artery embolization for uterine arteriovenous malformation is associated
      with placental abnormalities in the subsequent pregnancy: two cases report.
AB  - Uterine arteriovenous malformation (AVM) is generally associated with uterine
      trauma such as dilatation and curettage, therapeutic abortion, uterine surgery
      and uterine malignant tumors(1)). Uterine artery embolization (UAE) is performed
      on patients with uterine AVM who have desire for future pregnancy(2)). Some
      successful pregnancies were reported after UAE for uterine AVM(5,6)), however
      complication during pregnancy has not been described clearly. We herein for the
      first time report two cases of successful pregnancy and spontaneous delivery
      after UAE for uterine AVM who had placenta accreta and placental abruption
      respectively. Although successful pregnancy is possible after UAE for AVM,
      placenta abnormalities have to be considered during pregnancy and after delivery.

PMID- 24670674
TI  - Long-term survival after resection of metastases in the lungs and larynx
      originating from sigmoid colon cancer: report of a case.
AB  - Metastatic neoplasms in the larynx from remote primary tumors are uncommon, and
      laryngeal metastasis originating from the colorectum is extremely rare. We herein
      report a case of metastatic laryngeal carcinoma originating from sigmoid colon
      cancer in a 54-year-old female. Curative partial laryngectomy was performed, and
      the patient remains alive with a good quality of life and no signs of recurrence
      seven years and eight months after sigmoidectomy and four years and eight months
      after partial laryngectomy. 

PMID- 24670675
TI  - Neutrophil elastase inhibitor suppresses IL-17 based inflammation of murine
      experimental colitis.
AB  - BACKGROUND: Neutrophil elastase (NE) is a proteinase in granulocytes and plays an
      important role in the pathogenesis of inflammatory disorders. It has been
      reported that NE activity is elevated in both colonic mucosa and blood in
      inflammatory bowel disease (IBD) patients, and that it can act as an aggravating
      factor in IBD. To develop novel therapies for IBD, we examined the effects of an
      NE inhibitor, Elaspor(r), on murine experimental colitis. METHODS: Acute colitis
      was induced in BALB/c mice by administration of dextran sulfate sodium (DSS) in
      drinking water for 7 days. NE inhibitor was administered subcutaneously to mice
      prior to and during the induction of colitis. Disease activity index (DAI),
      colonic myeloperoxidase (MPO) activity, luminal NE activity, and mRNA expression
      in the colon were then investigated. RESULTS: Subcutaneous administration of NE
      inhibitor ameliorated the severity of DSS-induced colitis. NE activity was
      elevated in inflamed colon, and was reduced by NE inhibitor administration. mRNA
      expression levels of IL-17, a Th17-based inflammatory factor, was also decreased
      in the colon of NE inhibitor-administered mice. CONCLUSION: These results suggest
      that NE inhibitor ameliorated colonic inflammation by decreasing both the
      activity of NE and the effects of cytokine balance. Clinically, NE inhibitor
      improves injuries associated with systemic inflammatory response syndrome.
      Similarly, clinical use of this inhibitor would further clarify its usefulness in
      clinical colonic inflammation.

PMID- 24670676
TI  - The inhibitory effect of shakuyakukanzoto on K+ current in H9c2 cells.
AB  - Shakuyakukanzoto (shao-yao-gan-cao-tang) is a commonly used Chinese traditional
      herbal medicine for the treatment of acute pain with muscle cramp. However, its
      mechanism of action is unclear. We previously reported that a low concentration
      of Kanzo (licorice) and isoliquiritigenin, a component of licorice, inhibited the
      potassium (K(+)) current in H9c2 cells. Therefore, in the present study, we
      examined the effects of Shakuyakukanzoto, Shakuyaku or Kanzo on the K(+) current
      (IKur) in H9c2 cells. Shakuyakukanzoto inhibited IKur in a concentration
      dependent manner. The half-maximal concentration of Shakuyakukanzoto was
      approximately 1.3 mg/mL and the Hill coefficient was 1.2. The order of potency of
      inhibiting IKur was Kanzo>Shakuyakukanzoto>Shakuyaku. Glycyrrhizin, a major
      component of licorice, had no inhibitory effect on IKur. A small interfering RNA
      experiment indicated that IKur was most likely to be Kv2.1 in H9c2 cells. Our
      results suggest that Shakuyakukanzoto may normalize intracellular and
      extracellular K(+) balance by inhibiting IKur and reducing K(+) efflux, while the
      Na(+)-K(+) pump promotes K(+) influx into myofibers. Consequently, excess K(+)
      may be reduced from external space of myofibers. This may be a part of the
      Shakuyakukanzoto mechanism for improving muscle pain. 

PMID- 24670677
TI  - Confirmation bias in web-based search: a randomized online study on the effects
      of expert information and social tags on information search and evaluation.
AB  - BACKGROUND: The public typically believes psychotherapy to be more effective than
      pharmacotherapy for depression treatments. This is not consistent with current
      scientific evidence, which shows that both types of treatment are about equally
      effective. OBJECTIVE: The study investigates whether this bias towards
      psychotherapy guides online information search and whether the bias can be
      reduced by explicitly providing expert information (in a blog entry) and by
      providing tag clouds that implicitly reveal experts' evaluations. METHODS: A
      total of 174 participants completed a fully automated Web-based study after we
      invited them via mailing lists. First, participants read two blog posts by
      experts that either challenged or supported the bias towards psychotherapy.
      Subsequently, participants searched for information about depression treatment in
      an online environment that provided more experts' blog posts about the
      effectiveness of treatments based on alleged research findings. These blogs were
      organized in a tag cloud; both psychotherapy tags and pharmacotherapy tags were
      popular. We measured tag and blog post selection, efficacy ratings of the
      presented treatments, and participants' treatment recommendation after
      information search. RESULTS: Participants demonstrated a clear bias towards
      psychotherapy (mean 4.53, SD 1.99) compared to pharmacotherapy (mean 2.73, SD
      2.41; t173=7.67, P<.001, d=0.81) when rating treatment efficacy prior to the
      experiment. Accordingly, participants exhibited biased information search and
      evaluation. This bias was significantly reduced, however, when participants were
      exposed to tag clouds with challenging popular tags. Participants facing popular
      tags challenging their bias (n=61) showed significantly less biased tag selection
      (F2,168=10.61, P<.001, partial eta squared=0.112), blog post selection
      (F2,168=6.55, P=.002, partial eta squared=0.072), and treatment efficacy ratings
      (F2,168=8.48, P<.001, partial eta squared=0.092), compared to bias-supporting tag
      clouds (n=56) and balanced tag clouds (n=57). Challenging (n=93) explicit expert
      information as presented in blog posts, compared to supporting expert information
      (n=81), decreased the bias in information search with regard to blog post
      selection (F1,168=4.32, P=.04, partial eta squared=0.025). No significant effects
      were found for treatment recommendation (Ps>.33). CONCLUSIONS: We conclude that
      the psychotherapy bias is most effectively attenuated-and even eliminated-when
      popular tags implicitly point to blog posts that challenge the widespread view.
      Explicit expert information (in a blog entry) was less successful in reducing
      biased information search and evaluation. Since tag clouds have the potential to
      counter biased information processing, we recommend their insertion.

PMID- 24670679
TI  - Improved performance of graphene transistors by strain engineering.
AB  - By means of numerical simulation, in this work we study the effects of uniaxial
      strain on the transport properties of strained graphene heterojunctions and
      explore the possibility of achieving good performance of graphene transistors
      using these hetero-channels. It is shown that a finite conduction gap can open in
      the strain junctions due to strain-induced deformation of the graphene
      bandstructure. These hetero-channels are then demonstrated to significantly
      improve the operation of graphene field-effect transistors (FETs). In particular,
      the ON/OFF current ratio can reach a value of over 10(5). In graphene normal
      FETs, the transconductance, although reduced compared to the case of unstrained
      devices, is still high, while good saturation of current can be obtained. This
      results in a high voltage gain and a high transition frequency of a few hundreds
      of GHz for a gate length of 80 nm. In graphene tunneling FETs, subthreshold
      swings lower than 30 mV /dec, strong nonlinear effects such as gate-controllable
      negative differential conductance, and current rectification are observed. 

PMID- 24670680
TI  - The art of harmonious delegation.

PMID- 24670678
TI  - Identification and characterization of a suite of tumor targeting peptides for
      non-small cell lung cancer.
AB  - Tumor targeting ligands are emerging components in cancer therapies. Widespread
      use of targeted therapies and molecular imaging is dependent on increasing the
      number of high affinity, tumor-specific ligands. Towards this goal, we biopanned
      three phage-displayed peptide libraries on a series of well-defined human non
      small cell lung cancer (NSCLC) cell lines, isolating 11 novel peptides. The
      peptides show distinct binding profiles across 40 NSCLC cell lines and do not
      bind normal bronchial epithelial cell lines. Binding of specific peptides
      correlates with onco-genotypes and activation of particular pathways, such as
      EGFR signaling, suggesting the peptides may serve as surrogate markers.
      Multimerization of the peptides results in cell binding affinities between 0.0071
      40 nM. The peptides home to tumors in vivo and bind to patient tumor samples.
      This is the first comprehensive biopanning for isolation of high affinity
      peptidic ligands for a single cancer type and expands the diversity of NSCLC
      targeting ligands.

PMID- 24670681
TI  - Whole-genome sequencing in newborn screening programs.
AB  - The availability of whole-genome sequencing (WGS) is likely to change the
      practice of population screening programs such as newborn screening (NBS). This
      Commentary raises key ethical, legal, and social issues surrounding WGS in NBS
      and suggests a need for deliberation regarding the policy challenges of
      introducing sequencing in such programs. Any change in the goals of NBS programs
      should be discussed carefully and should represent the best interests of the
      child. 

PMID- 24670682
TI  - Comment on "drug discovery: turning the titanic".
AB  - The pathobiology-based approach to research and development has been the dominant
      paradigm for successful drug discovery over the last decades. We propose that the
      molecular and cellular events that govern a resolving, rather than an evolving,
      disease may reveal new druggable pathways. 

PMID- 24670683
TI  - Author response to comment on "drug discovery: turning the titanic".
AB  - In the face of poorly understood disease complexity, a diversity of approaches is
      the best strategy. 

PMID- 24670684
TI  - Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease
      causes local IL-17-driven inflammatory bone loss.
AB  - Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with
      frequent microbial infections, is caused by mutations on the CD18 subunit of
      beta2 integrins. LAD-I is invariably associated with severe periodontal bone
      loss, which historically has been attributed to the lack of neutrophil
      surveillance of the periodontal infection. We provide an alternative mechanism by
      showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral
      pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA
      1 (CD11a/CD18)-deficient mice--which exhibit the LAD-I periodontal phenotype--was
      associated with excessive production of predominantly T cell-derived IL-17 in the
      periodontal tissue, although innate lymphoid cells also contributed to
      pathological IL-17 elevation in the LFA-1-deficient mice. Local treatment with
      antibodies to IL-17 or IL-23 in LFA-1-deficient mice not only blocked
      inflammatory periodontal bone loss but also caused a reduction in the total
      bacterial burden, suggesting that the IL-17-driven pathogenesis of LAD-I
      periodontitis leads to dysbiosis. Therefore, our findings support an IL-17
      targeted therapy for periodontitis in LAD-I patients.

PMID- 24670685
TI  - Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer.
AB  - Resistance to aromatase inhibitors (AIs) is a major clinical problem in the
      treatment of estrogen receptor (ER)-positive breast cancer. In two breast cancer
      cell line models of AI resistance, we identified widespread DNA hyper- and
      hypomethylation, with enrichment for promoter hypermethylation of developmental
      genes. For the homeobox gene HOXC10, methylation occurred in a CpG shore, which
      overlapped with a functional ER binding site, causing repression of HOXC10
      expression. Although short-term blockade of ER signaling caused relief of HOXC10
      repression in both cell lines and breast tumors, it also resulted in concurrent
      recruitment of EZH2 and increased H3K27me3, ultimately transitioning to increased
      DNA methylation and silencing of HOXC10. Reduced HOXC10 in vitro and in
      xenografts resulted in decreased apoptosis and caused antiestrogen resistance.
      Supporting this, we used paired primary and metastatic breast cancer specimens to
      show that HOXC10 was reduced in tumors that recurred during AI treatment. We
      propose a model in which estrogen represses apoptotic and growth-inhibitory genes
      such as HOXC10, contributing to tumor survival, whereas AIs induce these genes to
      cause apoptosis and therapeutic benefit, but long-term AI treatment results in
      permanent repression of these genes via methylation and confers resistance.
      Therapies aimed at inhibiting AI-induced histone and DNA methylation may be
      beneficial in blocking or delaying AI resistance. 

PMID- 24670686
TI  - DNA repair pathway gene expression score correlates with repair proficiency and
      tumor sensitivity to chemotherapy.
AB  - Mutagenesis is a hallmark of malignancy, and many oncologic treatments function
      by generating additional DNA damage. Therefore, DNA damage repair is centrally
      important in both carcinogenesis and cancer treatment. Homologous recombination
      (HR) and nonhomologous end joining are alternative pathways of double-strand DNA
      break repair. We developed a method to quantify the efficiency of DNA repair
      pathways in the context of cancer therapy. The recombination proficiency score
      (RPS) is based on the expression levels for four genes involved in DNA repair
      pathway preference (Rif1, PARI, RAD51, and Ku80), such that high expression of
      these genes yields a low RPS. Carcinoma cells with low RPS exhibit HR suppression
      and frequent DNA copy number alterations, which are characteristic of error-prone
      repair processes that arise in HR-deficient backgrounds. The RPS system was
      clinically validated in patients with breast or non-small cell lung carcinomas
      (NSCLCs). Tumors with low RPS were associated with greater mutagenesis, adverse
      clinical features, and inferior patient survival rates, suggesting that HR
      suppression contributes to the genomic instability that fuels malignant
      progression. This adverse prognosis associated with low RPS was diminished if
      NSCLC patients received adjuvant chemotherapy, suggesting that HR suppression and
      associated sensitivity to platinum-based drugs counteract the adverse prognosis
      associated with low RPS. Therefore, RPS may help oncologists select which
      therapies will be effective for individual patients, thereby enabling more
      personalized care. 

PMID- 24670688
TI  - Embracing the challenges of HIV-TB co-infection in children.

PMID- 24670687
TI  - Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation
      on multipolar spindles.
AB  - The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell
      death in tumors as a consequence of mitotic arrest, as it does at concentrations
      routinely used in cell culture. However, we determine here that paclitaxel levels
      in primary breast tumors are well below those required to elicit sustained
      mitotic arrest. Instead, cells in these lower concentrations of drug proceed
      through mitosis without substantial delay and divide their chromosomes on
      multipolar spindles, resulting in chromosome missegregation and cell death.
      Consistent with these cell culture data, most mitotic cells in primary human
      breast cancers contain multipolar spindles after paclitaxel treatment. Contrary
      to the previous hypothesis, we find that mitotic arrest is dispensable for tumor
      regression in patients. These results demonstrate that mitotic arrest is not
      responsible for the efficacy of paclitaxel, which occurs because of chromosome
      missegregation on highly abnormal, multipolar spindles. This mechanistic insight
      may be used to improve selection of future antimitotic drugs and to identify a
      biomarker with which to select patients likely to benefit from paclitaxel. 

PMID- 24670689
TI  - Towards elimination in industrialised countries: expanding diagnosis and
      treatment of LTBI among immigrants.

PMID- 24670690
TI  - Tuberculosis in human immunodeficiency virus-infected children starting
      antiretroviral therapy in Cote d'Ivoire.
AB  - SETTING: In Cote d'Ivoire, more than 2000 human immunodeficiency virus (HIV)
      infected children aged <15 years were started on antiretroviral therapy (ART)
      during 2004-2008. OBJECTIVES: To estimate tuberculosis (TB) incidence and
      determinants among ART enrollees. DESIGN: A nationally representative
      retrospective cohort study among 2110 children starting ART during 2004-2008 at
      29 facilities. RESULTS: At ART initiation, the median age was 5.1 years; 82% had
      World Health Organization Stage III/IV, median CD4% was 11%, 42% were severely
      undernourished (weight-for-age Z-score [WAZ] <-3), and 150 (7%) were taking anti
      tuberculosis treatment. Documentation of TB screening before ART declined from
      63% to 46% during 2004-2008. Children taking anti-tuberculosis treatment at ART
      enrollment had a lower median CD4% (9.0% vs. 11.0%, P = 0.037) and a higher
      prevalence of WAZ <-3 (59% vs. 40%, P < 0.001). Among children considered TB-free
      at ART enrollment, TB incidence was 6.28/100 child-years during days 0-90 of ART,
      declining to 0.56/100 child-years after 180 days. Children with one unit higher
      WAZ at ART enrollment had 13% lower TB incidence (adjusted HR 0.87, 95%CI 0.77
      1.00, P= 0.047). CONCLUSIONS: Ensuring clinician compliance with TB screening
      before ART and ensuring earlier ART initiation before children suffer from
      advanced HIV disease and nutritional compromise might reduce TB morbidity during
      ART.

PMID- 24670691
TI  - The effect of topical calcipotriol or zinc on tuberculin skin tests in
      hospitalised South African children.
AB  - BACKGROUND: The tuberculin skin test (TST) is used to help diagnose tuberculosis
      (TB) in acutely ill hospitalised children. OBJECTIVE To investigate the potential
      augmentative effect of topical calcipotriol (a vitamin D analogue) or zinc on TST
      induration. METHODS: Three TSTs were performed among 64 hospitalised children;
      each site was covered with topical aqueous cream (control), calcipotriol or zinc
      and assessed 24 and 48 h later by investigators blinded to all topical
      applications. RESULTS: TSTs were reactive in 15 (23.4%) children, of whom 13
      (20.3%) were TST-positive. Topical calcipotriol and zinc induced TST positivity
      in two children with reactive but negative control TSTs. These treatments,
      however, did not significantly increase TST positivity rates. In children with
      reactive TSTs, the median 48 h induration diameter was not significantly
      different between the control, calcipotriol- or zinc-treated groups, which were
      respectively 12.0 (25%-75% IQR 5.0 - 18.0), 14.0 (25%-75% IQR 10.0 - 15.0) and
      12.0 (25%-75% IQR 8.0 - 15.0) mm. Topical treatments did not induce TST
      reactivity or TST positivity in children with culture-confirmed TB disease (n =
      4), human immunodeficiency virus infection (n= 18) or kwashiorkor (n = 9).
      CONCLUSIONS: Topical calcipotriol or zinc does not induce TST reactivity or
      significantly increase TST positivity rates in acutely ill hospitalised children.
      However, further studies are required to assess the effects of topical treatments
      on TST positivity in severely malnourished children.

PMID- 24670692
TI  - Non-response to the intensive phase of anti-tuberculosis treatment in children:
      evaluation and outcome [Short Communication].
AB  - The present study evaluates the causes for the persistence of symptoms and
      radiological signs after at least 2 months of intensive anti-tuberculosis
      treatment in children. In this prospective observational study, 26 paediatric
      patients with partial or no response to anti-tuberculosis treatment after the 2
      month intensive phase were enrolled. After a detailed history and workup, it was
      found that 9 (34.6%) patients had a wrong initial diagnosis, while 12 (46.2%) had
      either received inadequate treatment or had complications requiring prolonged
      treatment; 5 (19.2%) failed to respond. Failure to respond to anti-tuberculosis
      treatment in paediatric tuberculosis seems to be over-diagnosed. 

PMID- 24670693
TI  - Aligning US health and immigration policy to reduce the incidence of
      tuberculosis.
AB  - OBJECTIVES: Tuberculosis (TB) is a significant public health issue, claiming 1.4
      million lives worldwide in 2011. Using data from the 2009-2010 National Health
      Interview Survey, we examine variation in 'having heard of TB' (HTB) by global
      region of birth and health insurance status. METHODS: Cross-sectional analysis
      with bivariate comparisons and multivariate logistic regression to evaluate how
      adults differed in reported HTB, controlling for global region of birth. RESULTS:
      HTB rates ranged from 63.4% of adults born in Asia to 88.6% born in Europe.
      Uninsured immigrants had the lowest rate of HTB, ranging from a low of 50.1% of
      uninsured adults born in Asia to 77.6% born in Europe and 90.8% of US-born
      uninsured adults. Longer length of time in the United States (>5 years) was
      significantly associated with increased likelihood of HTB, as did being of Asian
      race/ethnicity and being male. Those with private health insurance coverage had
      the highest rates of HTB. CONCLUSIONS: To reduce persistent TB, public health
      program directors and policy makers must 1) recognize the variation in HTB by
      global region of birth and prioritize areas with the lowest HTB rates, and 2)
      reduce barriers to health insurance coverage by eliminating the 5-year ban for
      public program coverage for new immigrants.

PMID- 24670694
TI  - Preventing tuberculosis in the foreign-born population of Canada: a mathematical
      modelling study.
AB  - BACKGROUND: Foreign-born persons in Canada contribute 67% of all tuberculosis
      (TB) cases annually, but represent only 21% of the total population. Molecular
      epidemiological studies suggest that most foreign-born TB cases result from the
      reactivation of latent tuberculous infection (LTBI) acquired before immigration.
      OBJECTIVE: To estimate the effect on incidence of a prevention strategy that
      would screen selected immigrants at arrival for LTBI and offer preventive
      treatment to those who test positive. DESIGN: A deterministic model was developed
      to quantify the incidence of active TB in immigrants to Canada and validated with
      national immigration and TB case data. RESULTS: Model simulations suggested that
      it would be optimal to screen and treat LTBI in new immigrants from countries of
      birth with an estimated TB incidence rate in excess of 50 per 100 000 person
      years. If this strategy had been implemented in 1986, the national TB incidence
      rate would have fallen by 18.5%, from 5.4 to 4.4 cases per 100 000 population by
      2002. CONCLUSION: This study suggests that screening and treating LTBI in foreign
      born persons from high TB incidence countries is the most effective strategy in
      terms of total persons screened and treated and percentage reduction in national
      incidence.

PMID- 24670695
TI  - Added value of interferon-gamma release assays in screening for tuberculous
      infection in the Netherlands.
AB  - BACKGROUND: Interferon-gamma release assays (IGRAs) are reported to be more
      specific for the diagnosis of latent tuberculous infection (LTBI) than the
      tuberculin skin test (TST). The two-step procedure, TST followed by an IGRA, is
      reported to be cost-effective in high-income countries, but it requires more
      financial resources. OBJECTIVE: To assess the added value of IGRA compared to TST
      alone in the Netherlands. METHODS: Test results and background data on persons
      tested with an IGRA were recorded by the Public Municipal Health Services in a
      web-based database. The number of persons diagnosed with LTBI using different
      screening algorithms was calculated. RESULTS: In those tested with an IGRA, at
      least 60% of persons who would have been diagnosed with LTBI based on TST alone
      had a negative IGRA. Among those with a TST reaction below the cut-off for the
      diagnosis of LTBI, 13% had a positive IGRA. For 41% of persons tested with an
      IGRA after TST, the IGRA influenced whether or not an LTBI diagnosis would be
      made. CONCLUSION: With the IGRA as reference standard, a high proportion of
      persons in low-prevalence settings are treated unnecessarily for LTBI if tested
      with TST alone, while a small proportion eligible for preventive treatment are
      missed. Incremental costs of the two-step strategy seem to be balanced by the
      improved targeting of preventive treatment.

PMID- 24670696
TI  - Risk factors for treatment default in close contacts with latent tuberculous
      infection.
AB  - OBJECTIVE: 1) To characterize risk factors for non-completion of latent
      tuberculous infection treatment (LTBIT), and 2) to assess the impact of LTBIT
      regimens on subsequent risk of tuberculosis (TB). METHODS: Close contacts of
      adults aged ?15 years with pulmonary TB were prospectively enrolled in a multi
      center study in the United States and Canada from January 2002 to December 2006.
      Close contacts of TB patients were screened and cross-matched with TB registries
      to identify those who developed active TB. RESULTS: Of 3238 contacts screened,
      1714 (53%) were diagnosed with LTBI. Preventive treatment was recommended in 1371
      (80%); 1147 (84%) initiated treatment, of whom 723 (63%) completed it. In
      multivariate analysis, study site, initial interview sites other than a home or
      health care setting and isoniazid preventive treatment (IPT) were significantly
      associated with non-completion of LTBIT. Fourteen TB cases were identified in
      contacts, all of whom initiated IPT: two TB cases among persons who received ?6
      months of IPT (66 cases/100 000 person-years [py]), and nine among those who
      received 0-5 months (median 2 months) of IPT (792 cases/100 000 py, P < 0.001);
      data on duration of IPT were not available for three cases. CONCLUSION: Only 53%
      (723/1371) of close contacts for whom IPT was recommended actually completed
      treatment. Close contacts were significantly less likely to complete LTBIT if
      they took IPT. Less than 6 months of IPT was associated with increased risk of
      active TB.

PMID- 24670697
TI  - The 'either test positive' strategy for latent tuberculous infection before anti
      tumour necrosis factor treatment.
AB  - SETTING: A ttertiary referral centre in South Korea. OBJECTIVES: The 'either test
      positive' strategy, incorporating both the tuberculin skin test (TST) and the T
      SPOT((r)).TB(T-SPOT) assay, was evaluated as a novel method for diagnosing latent
      tuberculous infection (LTBI) before treatment with anti-tumour necrosis factor
      (TNF) in patients with immune-mediated inflammatory diseases. DESIGN: From June
      2008 to April 2012, 430 patients received anti-TNF treatment at our institution.
      TST and T-SPOT were performed simultaneously at baseline. LTBI was defined as a
      positive TST or a positive T-SPOT result. RESULTS: The positivity rates for the
      TST and T-SPOT assays were respectively 19.1% (82/430) and 44.2% (190/430),
      yielding an LTBI-positive rate of 48.6% (209/430). LTBI treatment was initiated
      in 46.0% (198/430) of patients and was completed by 89.4% (177/198). During
      follow-up (median 884 days), 0.9% (4/430) of the patients developed active
      tuberculosis (TB). All four TB patients were TST-negative at baseline, although
      two received LTBI treatment based on the baseline positive T-SPOT assay results.
      CONCLUSIONS: The either test positive strategy is a valid method for diagnosing
      LTBI before anti-TNF treatment, although it is not clear whether it is superior
      to other strategies.

PMID- 24670698
TI  - Impact of the Xpert((r)) MTB/RIF molecular test on the late diagnosis of
      pulmonary tuberculosis.
AB  - We analysed the impact of the Xpert((r)) MTB/RIF molecular test on health-care
      diagnostic delay among tuberculosis patients. Diagnostic delay was 17.2 days
      (standard deviation 23.2, median 10 days). Of 128 patients recruited into the
      study, 60 (47%) were smear-negative; of these, 40 (67%) were Xpert-positive and
      were started on treatment without culture. The sensitivity of smear microscopy
      was 53% compared with 82% for Xpert. In smear-negative patients, delay in Xpert
      positive and -negative patients was respectively 15.5 +/- 13.2 and 25.5 +/- 12.5
      days (P = 0.002). We conclude that Xpert results were significantly associated
      with shorter health-care diagnostic delay, particularly in smear-negative
      patients. 

PMID- 24670699
TI  - Successes, challenges and lessons from a novel deployment of Xpert((r)) MTB/RIF
      at a major South African public event [Short Communication].
AB  - In a mobile deployment of Xpert((r)) MTB/RIF (Xpert) at the public event for 2012
      South African World TB Day, Xpert testing was offered to tuberculosis (TB)
      symptomatic clients from gold mining and surrounding communities. Considerations
      before implementation included effective TB symptom screening; safe, effective
      sputum collection; uninterrupted electricity supply; stringent instrument
      verification and provision of on-site results. Public event Xpert testing is
      feasible; however, the case-finding rate was very low (0.7%). We recommend
      exploring enhanced symptom screening algorithms to improve pre-test probability,
      cost-effectiveness analysis, exploring alternate electrical fail-safes and on
      site data connectivity and improving management of client expectations. 

PMID- 24670700
TI  - Community-based treatment of drug-resistant tuberculosis in Khayelitsha, South
      Africa.
AB  - SETTING: Khayelitsha, South Africa, a peri-urban township with high burdens of
      tuberculosis (TB), drug-resistant tuberculosis (DR-TB), and human
      immunodeficiency virus (HIV) infection. OBJECTIVE: To describe case detection and
      patient outcomes in a community-based DR-TB programme. DESIGN: DR-TB management
      was integrated into primary health care in Khayelitsha from 2007 onwards.
      Implementation was incremental, and included training and clinician support,
      counselling and home visits, tuberculous infection control, a local in-patient
      service, and routine monitoring. Patients received treatment rapidly through
      their local clinic, and were only hospitalised if clinically unwell. RESULTS: DR
      TB case notification (any rifampicin resistance) increased from 28 per 100 000
      population per year (2005-2007) to 55/100 000/year in 2009-2011 (72% HIV
      infected). From 2008 to 2011, 754 patients received treatment (86% of those
      diagnosed). The median time between diagnostic sputum and treatment decreased
      over the years of implementation to 27 days in 2011 (P < 0.001). Treatment
      success was 52% in 2010, with 31% default, 13% death and 4% treatment failure.
      Two-year survival was 65%, with poorer survival in those with HIV (HR 2.0, 95%CI
      1.4-2.8), second-line drug resistance (HR 3.3, 95%CI 2.2-4.8), and diagnosis in
      earlier programme years (HR 1.4, 95%CI 1.1-2.0). CONCLUSION: Community-based DR
      TB management is feasible, and contributes to improved case detection, reduced
      treatment delay and improved survival. Treatment outcomes remain poor,
      highlighting the poor efficacy, tolerability and lengthy duration of current
      treatment.

PMID- 24670701
TI  - Are we justified in treating for multidrug-resistant tuberculosis based on
      positive follow-up smear results?
AB  - SETTING: National Institute for Research in Tuberculosis, India. OBJECTIVE: To
      assess, among new culture-confirmed smear-positive pulmonary tuberculosis (TB)
      patients, the proportion of follow-up smear-positives that were culture-negative
      (S+C-) by month of follow-up examination, human immunodeficiency virus (HIV)
      status, pre-treatment drug susceptibility status and smear grading. DESIGN: We
      extracted follow-up smear (fluorescence microscopy) and culture (Lowenstein
      Jensen) results of patients enrolled in clinical trials from January 2000 to
      August 2012 and treated with the WHO Category I regimen (2EHRZ3/4HR3). RESULTS:
      Of 520 patients, including 176 who were HIV-infected, respectively 199, 81, 47
      and 43 were smear-positive at months 2, 4, 5 and 6; of these, respectively 138
      (69%), 62 (75%), 32 (68%) and 27 (63%) were culture-negative. The S+C- phenomenon
      was more pronounced among '1+ positive' patients than in 2+ or 3+ positive
      patients and in 'pan-susceptible' patients than in those with any resistance, and
      did not vary by HIV status. CONCLUSION: Nearly two thirds of patients with follow
      up smears positive at months 5 and 6 were culture-negative. Starting multidrug
      resistant TB (MDR-TB) treatment empirically based on smear results, even in
      resource-limited settings, is incorrect and can have hazardous consequences.
      There is an urgent need to revisit the WHO recommendation concerning empirical
      MDR-TB treatment.

PMID- 24670702
TI  - Characterisation of pyrazinamide-resistant Mycobacterium tuberculosis strains
      isolated in Poland and Germany.
AB  - BACKGROUND: Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug
      that is generally administered with isoniazid, rifampicin, ethambutol and
      streptomycin. OBJECTIVE: To analyse the correlation between phenotypic resistance
      to PZA and genotype to find out whether the great diversity in pncA mutations is
      epidemiologically useful in tracing the transmission of PZA-resistant
      Mycobacterium tuberculosis strains among patients. MATERIALS AND METHODS: The
      study included 71 PZA-resistant M. tuberculosis strains isolated from 62 Polish
      and 9 German patients. All strains were analysed using minimal inhibitory
      concentration value determination, pncA mutation analysis, spoligotyping, 24-loci
      mycobacterial interspersed repetitive units-variable number of tandem repeats
      (MIRU-VNTR) and insertion sequence (IS) 6110 restriction fragment length
      polymorphism (RFLP) fingerprinting. RESULTS: In 63 isolates, 37 (88.7%) different
      mutations in the pncA gene were observed, 13 of which had not been previously
      reported; 11 molecular families with the same MIRU-VNTR and IS6110-RFLP pattern
      were found. The same mutation was identified in three families, while different
      ones were identified in the remaining families. CONCLUSION: Mutations in the pncA
      gene are a major cause of PZA resistance in M. tuberculosis. pncA mutation
      analysis can be used to obtain valuable additional information, but should be
      applied with caution for epidemiological analysis.

PMID- 24670704
TI  - Change in serum CXCL10 levels during anti-tuberculosis treatment depends on
      vitamin D status [Short Communication].
AB  - Serum levels of the inflammatory C-X-C motif chemokine 10 (CXCL10) are raised in
      tuberculosis (TB). CXCL10 gene expression is downregulated in monocytes by
      metabolically active vitamin D3 (1,25dihydroxy vitamin D). Stratification of
      patients by serum 25hydroxyvitamin D (25[OH]D) levels at baseline showed that
      treatment-induced decrease in CXCL10 occurred in those with 'insufficient' and
      'deficient' but not in those with 'optimal' levels. In the deficient group,
      25(OH)D showed an inverse correlation with CXCL10 levels. CXCL10 may thus be a
      useful biomarker for the follow-up of response to treatment. However, CXCL10
      levels should be interpreted taking into account the baseline serum vitamin D
      levels of the TB patients. 

PMID- 24670703
TI  - Evaluation of indirect drug susceptibility testing using the MODS assay for the
      detection of XDR-TB in China.
AB  - SETTING: The First Affiliated Hospital of Nanchang University and the Chest
      Hospital of Jiangxi Province, Jiangxi, China. OBJECTIVE: To assess the
      performance and feasibility of the microscopic observation drug susceptibility
      (MODS) assay for the simultaneous detection of multidrug-resistant (MDR) and
      extensively drug-resistant tuberculosis (XDR-TB) in a high-burden, resource
      limited setting. METHODS: A total of 208 archived clinical isolates of
      Mycobacterium tuberculosis were used to compare MODS with the conventional
      proportion method for the rapid detection of resistance to rifampicin (RMP) and
      isoniazid (INH), as well as to the second-line drugs ofloxacin (OFX) and
      kanamycin (KM). RESULTS: Sensitivity was respectively 94.5%, 91%, 96.2% and 91.5%
      for RMP, INH, OFX and KM, and specificity was respectively 97.5%, 96%, 100% and
      98.7%. Results for MODS were obtained in a median time of 7 days (range 5-17).
      CONCLUSION: The MODS assay offers a simple, rapid, economical and feasible method
      for the detection of M. tuberculosis resistance to first- and second-line drugs
      in resource-limited settings.

PMID- 24670705
TI  - Value of procalcitonin in differentiating pulmonary tuberculosis from other
      pulmonary infections: a meta-analysis.
AB  - OBJECTIVES: To systematically and quantitatively summarise the current evidence
      on the utility of the procalcitonin test (PCT) in discriminating pulmonary
      tuberculosis (TB) from other pulmonary infections. METHODS: We searched MEDLINE,
      EMBASE and the Cochrane database up to August 2013 for studies that reported the
      performance of PCT alone or compared with other biomarkers in diagnosing
      pulmonary TB. We summarised PCT using forest plots, hierarchical summary receiver
      operating characteristic curves and bivariate random effects models. RESULTS: We
      found nine qualifying studies covering 951 episodes of suspected TB along with
      426 confirmed TB cases. The bivariate pooled sensitivity and specificity of PCT
      to distinguish TB from non-TB were respectively 42% (95%CI 30-56) and 87% (95%CI
      63-96). The bivariate pooled sensitivity and specificity for PCT in
      distinguishing TB from bacterial pneumonia were respectively 78% (95%CI 67-86)
      and 85% (95%CI 78-90). Low heterogeneity was noted in studies comparing TB with
      bacterial pneumonia patients. CONCLUSION: The results suggest consistently
      acceptable sensitivity and specificity of the PCT test in distinguishing TB from
      bacterial pneumonia. However, given the imperfect sensitivity and specificity of
      the test, medical decisions should be based on both the PCT test results as well
      as on clinical findings.

PMID- 24670706
TI  - Extra-pulmonary tuberculosis: differential aspects and role of 16S-rRNA in urine.
AB  - BACKGROUND: Early diagnosis of extra-pulmonary tuberculosis (EPTB) is important
      for successful treatment. METHODS: All cases of EPTB diagnosed at Ramon y Cajal
      Hospital, Madrid, Spain, from 1997 to 2008 were analysed and compared with
      pulmonary tuberculosis (PTB) patients to identify differential parameters that
      could serve to predict the presence of EPTB at initial presentation. Different
      microbiological techniques were analysed, including amplification of 16S-rRNA in
      urine. RESULTS: During the study period, 814 cases of TB were diagnosed at our
      centre; 330 (40.5%) were EPTB. Concomitant PTB was detected in 45% of EPTB cases.
      The main clinical forms of EPTB were lymphadenitis (86, 26%), miliary TB (60,
      18%), and multifocal TB (43, 13%). Variables independently associated with EPTB
      were human immunodeficiency virus (HIV) infection (OR 3.6, 95%CI 2.4-5.4), older
      age (>60 years) (OR 3.7, 95%CI 2.5-5.6) and mortality (OR 2.9, 95%CI 1.3-6.3).
      16S-rRNA in urine was performed in 82 EPTB patients (25%), among whom a positive
      result was obtained in 70%; in the PTB group, a positive result was found in 5 of
      28 patients (18%) (P <0.001). CONCLUSIONS: HIV infection and older age appear to
      be the main risk factors associated with EPTB. In this study, mortality was
      significantly higher in patients with EPTB. A positive 16S-rRNA test result in
      urine is a useful marker of EPTB.

PMID- 24670707
TI  - Predictors of paradoxical tuberculoma in tuberculous meningitis.
AB  - SETTING: A tertiary care teaching hospital in Lucknow, India. OBJECTIVE: To
      evaluate the frequency and predictors of paradoxical tuberculoma in definite
      tuberculous meningitis (TBM) and its influence on TBM outcome. DESIGN:
      Demographic, clinical, biochemical, cerebrospinal fluid (CSF) findings, CD4
      counts and magnetic resonance imaging (MRI) findings of 34 patients with definite
      TBM included were noted. The patients received four-drug anti-tuberculosis
      treatment and prednisolone. They were followed up clinically and radiologically
      at 3 and 6 months; serum chemistry, CD4 counts and CSF were tested at 3 months.
      Functional outcome was defined on the basis of the Barthel index score.
      Predictors of paradoxical response were evaluated using univariate and
      multivariate analysis. RESULTS: The median age of the patients was 33.5 years; 13
      were females. Of the 34 study participants, 22 patients developed paradoxical
      tuberculoma, mostly within 3 months of initiating anti-tuberculosis treatment.
      Paradoxical tuberculoma was associated with clinical deterioration in 12
      patients. Bacille Calmette-Guerin vaccination, higher CSF glucose and abnormal
      baseline MRI were associated with paradoxical tuberculoma in univariate analysis.
      After adjustment of covariates, only female sex was independently associated with
      paradoxical tuberculoma (OR 0.06, 95%CI 0.004-0.79, P= 0.03). Paradoxical
      response, however, did not influence 6-month outcome. CONCLUSION: Paradoxical
      tuberculoma occurs in two thirds of patients with definite TBM, and in 50% it is
      asymptomatic. Females are more susceptible to paradoxical tuberculoma; however, 6
      month outcome is not influenced by paradoxical tuberculoma.

PMID- 24670708
TI  - Smoking increases risk of recurrence after successful anti-tuberculosis
      treatment: a population-based study.
AB  - OBJECTIVE: To investigate whether tobacco smoking increases the risk of
      tuberculosis (TB) recurrence and identify factors associated with TB recurrence
      among adults who had successfully completed anti-tuberculosis treatment in
      Taipei, Taiwan. METHODS: Recurrence was defined as a new clinical or
      microbiological diagnosis of TB requiring the start of a new course of treatment
      in a patient who had satisfactorily completed treatment for a previous TB
      episode. Cox proportional hazard models were used to calculate adjusted hazard
      ratios (aHRs) for recurrence. RESULTS: We followed 5567 adults for recurrence
      after successful anti-tuberculosis treatment. The mean age was 58.5 years; 62.9%
      were male. Overall, 84 (1.5%) had a recurrence of TB during follow-up. The
      incidence of TB recurrence was 4.9 episodes/1000 person-years of follow-up. Cox
      proportional hazards regression showed that after controlling for other
      variables, the risk of TB recurrence among subjects who smoked >10 cigarettes a
      day was double that of never/former smokers. Other independent risk factors
      significantly associated with TB recurrence were homelessness (aHR 3.75, 95%CI
      1.17-12.07), presence of comorbidities (aHR 2.66, 95%CI 1.22-5.79) and a positive
      acid-fast bacilli smear (aHR 2.27, 95%CI 1.47-3.49). CONCLUSION: Smoking >10
      cigarettes a day was significantly associated with TB recurrence. To reduce the
      risk of recurrence, we recommend including effective measures of smoking
      cessation in TB control programmes, as recommended by the World Health
      Organization Stop TB Strategy.

PMID- 24670709
TI  - Home environmental tobacco smoke exposure in Canadian children.
AB  - BACKGROUND: Children living with a smoker experience increased environmental
      tobacco smoke (ETS) exposure, even when the smoker refrains from smoking inside
      the house, compared to children not living with a smoker. Given the risks of ETS
      in children, it was hypothesized that households with children are less likely
      than those without children to experience home ETS exposure. DESIGN: Cross
      sectional analysis of the Canadian Community Health Survey 2009-2010 for the
      association between children aged <12 years in the household and home ETS
      exposure, using logistic regression and considering household education and
      income as confounders or effect modifiers. A subgroup analysis was conducted
      comparing younger child households (at least one child aged <6 years) to older
      child households (only children aged 6-11 years). RESULTS: Of 66 631 households
      included, home ETS exposure occurred in 25% of households without children and
      22% of households with children. Households with children were less likely than
      those without children to experience ETS exposure (OR 0.83, 95%CI 0.80-0.87).
      Effect modification by education and income was observed. No difference was
      observed in ETS exposure between older child and younger child households (OR
      0.98, 95%CI 0.91-1.05). CONCLUSION: Households with children are marginally less
      likely than households without children to experience home ETS exposure.

PMID- 24670711
TI  - Metabolically healthy obesity and the risk of cardiovascular disease and type 2
      diabetes: the Whitehall II cohort study.
AB  - AIM: The metabolically healthy obese (MHO) phenotype refers to obese individuals
      with a favourable metabolic profile. Its prognostic value is unclear and may
      depend on the health outcome being examined. We examined the association of MHO
      phenotype with incident cardiovascular disease (CVD) and type 2 diabetes. METHODS
      AND RESULTS: Body mass index and metabolic health, assessed using the Adult
      Treatment Panel-III (ATP-III) criteria, were assessed on 7122 participants (69.7%
      men) from the Whitehall II study, aged 39-63 years in 1991-93. Incident CVD
      (coronary heart disease or stroke) and type 2 diabetes were ascertained from
      medical screenings (every 5 years), hospital data, and registry linkage until
      2009. A total of 657 individuals (9.2% of the cohort) were obese and 42.5% of
      these were classified as MHO in 1991-93. Over the median follow-up of 17.4 years,
      there were 828 incident cases of CVD and 798 incident cases of type 2 diabetes.
      Compared with metabolically healthy normal weight individuals, MHO subjects were
      at increased risk for CVD (HR = 1.97, 95% CI: 1.38-2.80) and type 2 diabetes
      (3.25, 95% CI: 2.32-4.54). There was excess risk in metabolically unhealthy obese
      compared with MHO for type 2 diabetes (1.98, 95% CI: 1.39-2.83) but not CVD
      (1.23, 95% CI: 0.81-1.87). Treating all measures as time varying covariates
      produced similar findings. CONCLUSION: For type 2 diabetes, the MHO phenotype is
      associated with lower risk than the metabolically unhealthy obese, but for CVD
      the risk is as elevated in both obesity phenotypes.

PMID- 24670712
TI  - Expanding the indications for percutaneous mitral commmissurotomy in rheumatic
      mitral stenosis: look carefully at the commissures, and proceed cautiously and
      skilfully.

PMID- 24670710
TI  - Worldwide experience with a totally subcutaneous implantable defibrillator: early
      results from the EFFORTLESS S-ICD Registry.
AB  - AIMS: The totally subcutaneous implantable-defibrillator (S-ICD) is a new
      alternative to the conventional transvenous ICD system to minimize intravascular
      lead complications. There are limited data describing the long-term performance
      of the S-ICD. This paper presents the first large international patient
      population collected as part of the EFFORTLESS S-ICD Registry. METHODS AND
      RESULTS: The EFFORTLESS S-ICD Registry is a non-randomized, standard of care,
      multicentre Registry designed to collect long-term, system-related, clinical, and
      patient reported outcome data from S-ICD implanted patients since June 2009.
      Follow-up data are systematically collected over 60-month post-implant including
      Quality of Life. The study population of 472 patients of which 241 (51%) were
      enrolled prospectively has a mean follow-up duration of 558 days (range 13-1342
      days, median 498 days), 72% male, mean age of 49 +/- 18 years (range 9-88 years),
      42% mean left ventricular ejection fraction. Complication-free rates were 97 and
      94%, at 30 and 360 days, respectively. Three hundred and seventeen spontaneous
      episodes were recorded in 85 patients during the follow-up period. Of these
      episodes, 169 (53%) received therapy, 93 being for Ventricular
      Tachycardia/Fibrillation (VT/VF). One patient died of recurrent VF and severe
      bradycardia. Regarding discrete VT/VF episodes, first shock conversion efficacy
      was 88% with 100% overall successful clinical conversion after a maximum of five
      shocks. The 360-day inappropriate shock rate was 7% with the vast majority
      occurring for oversensing (62/73 episodes), primarily of cardiac signals (94% of
      oversensed episodes). CONCLUSION: The first large cohort of real-world data from
      an International patient S-ICD population demonstrates appropriate system
      performance with clinical event rates and inappropriate shock rates comparable
      with those reported for conventional ICDs. Clinical trial registration URL:
      http://www.clinicaltrials.gov. Unique identifier NCT01085435.

PMID- 24670713
TI  - Regenerative heart failure therapy headed for optimization.

PMID- 24670715
TI  - Context-aware personal navigation using embedded sensor fusion in smartphones.
AB  - Context-awareness is an interesting topic in mobile navigation scenarios where
      the context of the application is highly dynamic. Using context-aware computing,
      navigation services consider the situation of user, not only in the design
      process, but in real time while the device is in use. The basic idea is that
      mobile navigation services can provide different services based on different
      contexts-where contexts are related to the user's activity and the device
      placement. Context-aware systems are concerned with the following challenges
      which are addressed in this paper: context acquisition, context understanding,
      and context-aware application adaptation. The proposed approach in this paper is
      using low-cost sensors in a multi-level fusion scheme to improve the accuracy and
      robustness of context-aware navigation system. The experimental results
      demonstrate the capabilities of the context-aware Personal Navigation Systems
      (PNS) for outdoor personal navigation using a smartphone. 

PMID- 24670716
TI  - Derivation of land surface temperature for Landsat-8 TIRS using a split window
      algorithm.
AB  - Land surface temperature (LST) is one of the most important variables measured by
      satellite remote sensing. Public domain data are available from the newly
      operational Landsat-8 Thermal Infrared Sensor (TIRS). This paper presents an
      adjustment of the split window algorithm (SWA) for TIRS that uses atmospheric
      transmittance and land surface emissivity (LSE) as inputs. Various alternatives
      for estimating these SWA inputs are reviewed, and a sensitivity analysis of the
      SWA to misestimating the input parameters is performed. The accuracy of the
      current development was assessed using simulated Modtran data. The root mean
      square error (RMSE) of the simulated LST was calculated as 0.93  degrees C. This
      SWA development is leading to progress in the determination of LST by Landsat-8
      TIRS. 

PMID- 24670717
TI  - Latest trends in acoustic sensing.

PMID- 24670718
TI  - Minimal camera networks for 3D image based modeling of cultural heritage objects.
AB  - 3D modeling of cultural heritage objects like artifacts, statues and buildings is
      nowadays an important tool for virtual museums, preservation and restoration. In
      this paper, we introduce a method to automatically design a minimal imaging
      network for the 3D modeling of cultural heritage objects. This becomes important
      for reducing the image capture time and processing when documenting large and
      complex sites. Moreover, such a minimal camera network design is desirable for
      imaging non-digitally documented artifacts in museums and other archeological
      sites to avoid disturbing the visitors for a long time and/or moving delicate
      precious objects to complete the documentation task. The developed method is
      tested on the Iraqi famous statue "Lamassu". Lamassu is a human-headed winged
      bull of over 4.25 m in height from the era of Ashurnasirpal II (883-859 BC).
      Close-range photogrammetry is used for the 3D modeling task where a dense ordered
      imaging network of 45 high resolution images were captured around Lamassu with an
      object sample distance of 1 mm. These images constitute a dense network and the
      aim of our study was to apply our method to reduce the number of images for the
      3D modeling and at the same time preserve pre-defined point accuracy. Temporary
      control points were fixed evenly on the body of Lamassu and measured by using a
      total station for the external validation and scaling purpose. Two network
      filtering methods are implemented and three different software packages are used
      to investigate the efficiency of the image orientation and modeling of the statue
      in the filtered (reduced) image networks. Internal and external validation
      results prove that minimal image networks can provide highly accurate records and
      efficiency in terms of visualization, completeness, processing time (>60%
      reduction) and the final accuracy of 1 mm. 

PMID- 24670719
TI  - Contact region estimation based on a vision-based tactile sensor using a
      deformable touchpad.
AB  - A new method is proposed to estimate the contact region between a sensor and an
      object using a deformable tactile sensor. The sensor consists of a charge-coupled
      device (CCD) camera, light-emitting diode (LED) lights and a deformable touchpad.
      The sensor can obtain a variety of tactile information, such as the contact
      region, multi-axis contact force, slippage, shape, position and orientation of an
      object in contact with the touchpad. The proposed method is based on the
      movements of dots printed on the surface of the touchpad and classifies the
      contact state of dots into three types--A non-contacting dot, a sticking dot and
      a slipping dot. Considering the movements of the dots with noise and errors,
      equations are formulated to discriminate between the contacting dots and the non
      contacting dots. A set of the contacting dots discriminated by the formulated
      equations can construct the contact region. Next, a method is developed to detect
      the dots in images of the surface of the touchpad captured by the CCD camera. A
      method to assign numbers to dots for calculating the displacements of the dots is
      also proposed. Finally, the proposed methods are validated by experimental
      results.

PMID- 24670720
TI  - Microfiber optical sensors: a review.
AB  - With diameter close to or below the wavelength of guided light and high index
      contrast between the fiber core and the surrounding, an optical microfiber shows
      a variety of interesting waveguiding properties, including widely tailorable
      optical confinement, evanescent fields and waveguide dispersion. Among various
      microfiber applications, optical sensing has been attracting increasing research
      interest due to its possibilities of realizing miniaturized fiber optic sensors
      with small footprint, high sensitivity, fast response, high flexibility and low
      optical power consumption. Here we review recent progress in microfiber optical
      sensors regarding their fabrication, waveguide properties and sensing
      applications. Typical microfiber-based sensing structures, including biconical
      tapers, optical gratings, circular cavities, Mach-Zehnder interferometers and
      functionally coated/doped microfibers, are summarized. Categorized by sensing
      structures, microfiber optical sensors for refractive index, concentration,
      temperature, humidity, strain and current measurement in gas or liquid
      environments are reviewed. Finally, we conclude with an outlook for challenges
      and opportunities of microfiber optical sensors. 

PMID- 24670721
TI  - Use of an activity monitor and GPS device to assess community activity and
      participation in transtibial amputees.
AB  - This study characterized measures of community activity and participation of
      transtibial amputees based on combined data from separate accelerometer and GPS
      devices. The relationship between community activity and participation and
      standard clinical measures was assessed. Forty-seven participants were recruited
      (78% male, mean age 60.5 years). Participants wore the accelerometer and GPS
      devices for seven consecutive days. Data were linked to assess community activity
      (community based step counts) and community participation (number of community
      visits). Community activity and participation were compared across amputee K
      level groups. Forty-six participants completed the study. On average each
      participant completed 16,645 (standard deviation (SD) 13,274) community steps and
      16 (SD 10.9) community visits over seven days. There were differences between K
      level groups for measures of community activity (F(2,45) = 9.4, p < 0.001) and
      participation (F(2,45) = 6.9, p = 0.002) with lower functioning K1/2 amputees
      demonstrating lower levels of community activity and participation than K3 and K4
      amputees. There was no significant difference between K3 and K4 for community
      activity (p = 0.28) or participation (p = 0.43). This study demonstrated
      methodology to link accelerometer and GPS data to assess community activity and
      participation in a group of transtibial amputees. Differences in K-levels do not
      appear to accurately reflect actual community activity or participation in higher
      functioning transtibial amputees. 

PMID- 24670722
TI  - Synthesis of silver nanostructures by multistep methods.
AB  - The shape of plasmonic nanostructures such as silver and gold is vital to their
      physical and chemical properties and potential applications. Recently,
      preparation of complex nanostructures with rich function by chemical multistep
      methods is the hotspot of research. In this review we introduce three typical
      multistep methods to prepare silver nanostructures with well-controlled shapes,
      including the double reductant method, etching technique and construction of core
      shell nanostructures. The growth mechanism of double the reductant method is that
      different favorable facets of silver nanocrystals are produced in different
      reductants, which can be used to prepare complex nanostructures such as nanoflags
      with ultranarrow resonant band bandwidth or some silver nanostructures which are
      difficult to prepare using other methods. The etching technique can selectively
      remove nanoparticles to achieve the aim of shape control and is widely used for
      the synthesis of nanoflowers and hollow nanostructures. Construction of core
      shell nanostructures is another tool to control shape and size. The three methods
      can not only prepare various silver nanostructures with well-controlled shapes,
      which exhibit unique optical properties, such as strong surface-enhanced Raman
      scattering (SERS) signal and localized surface plasmon resonance (LSPR) effect,
      but also have potential application in many areas. 

PMID- 24670724
TI  - Biochemical and C-reactive protein alterations in myocardial infarction
      periodontitis patients.
AB  - Periodontitis (PD) is a risk factor for acute myocardial infarction (AMI). C
      reactive protein (CRP) is elevated in PD. The aim of this study was to
      investigate biochemical alterations among AMI with PD. Thirty non-AMI (25 non-PD
      and only 5 PD) and 30 AMI (13 PD and 17 non-PD) patients were participated. Serum
      CRP, tumor necrosis factor alpha (TNF-alpha), total cholesterol, low-density
      lipoprotein cholesterol, protein carbonyl (PC) contents, soluble vascular cell
      adhesion molecule-1 (sVCAM-1), adiponectin, creatine kinase, resistin, catalase
      and superoxide dismutase (SOD) levels were measured. AMI-PD elicited significant
      differences in percentage hypertension, diabetes, serum creatine kinase,
      cholesterol and low-density lipoprotein cholesterol. CRP among AMI-PD and non-AMI
      PD was increased by 73.4% and 31.3%, respectively. The level of PC contents was
      increased significantly among AMI-PD and non-AMI-PD by 47.62% and 33.3%,
      respectively. Catalase and SOD levels were significantly decreased in AMI-PD by
      33.7% and 34.1%, respectively; however, their levels among non-AMI-PD were
      significantly increased by 35.7% and 28%, respectively. TNF-alpha, sVCAM-1 and
      resistin levels among AMI-PD were increased by 134.3%, 68.8% and 25.5%,
      respectively; however, TNF-alpha and sVCAM-1 levels among non-AMI-PD were
      increased significantly by 21.4% and 29.4%, respectively. Adiponectin level
      produced insignificant changes. PD prevalence among AMI associated with elevated
      serum CRP, PC contents, sVCAM-1, TNF-alpha and resistin levels concurrent with
      declines in SOD and catalase enzymes. In conclusion, among nondiabetic,
      nonsmoking patients suffering from AMI, PD is highly prevalent and associated
      with elevated serum CRP, PC contents, sVCAM-1, TNF-alpha and resistin levels,
      associated with significant declines in antioxidant enzymes with insignificant
      change in serum adiponectin level.

PMID- 24670723
TI  - p38MAPK plays a crucial role in stromal-mediated tumorigenesis.
AB  - Neoplastic cells rely on the tumor microenvironment (TME) for survival and
      progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF)
      express factors that promote tumorigenesis that are collectively referred to as
      the senescence-associated secretory phenotype (SASP). Despite their importance in
      tumorigenesis, the mechanisms that control TME-derived factor expression remain
      poorly understood. Here, we address a key unanswered question: how the SASP is
      sustained in senescent fibroblasts and CAFs. We find that the mitogen-activated
      protein kinase p38 (p38MAPK) controls AUF1 occupancy on SASP mRNAs and thus
      controls their stability. The importance of this regulatory mechanism is
      underscored by our findings that stromal-specific p38MAPK inhibition abrogates
      the tumor-promoting activities of CAFs and senescent fibroblasts. Our data
      suggest that targeting SASP mRNA stability through inhibition of p38MAPK will
      significantly aid the development of clinical strategies to target the TME.
      SIGNIFICANCE: The TME plays a key role in tumorigenesis. We demonstrate that
      p38MAPK governs a posttranscriptional mechanism that sustains the protumorigenic
      SASP. Inhibition of p38MAPK abrogates the tumor-promoting activities of CAFs and
      senescent fibroblasts. Thus, p38MAPK is a TME-specific Achilles' heel that may be
      exploited as a new therapeutic target.

PMID- 24670725
TI  - Fundamental research is the key to eliminating TB.

PMID- 24670738
TI  - NASA missions bid for extensions.

PMID- 24670737
TI  - Federal red tape ties up marijuana research.

PMID- 24670739
TI  - Software patents await legal fate.

PMID- 24670741
TI  - Chile puts plan for science ministry on hold.

PMID- 24670740
TI  - Sister city inspires Pompeii rescue.

PMID- 24670743
TI  - Human evolution: The Neanderthal in the family.

PMID- 24670744
TI  - Immunology: A tolerant approach.

PMID- 24670749
TI  - WHO: Steering plans for neglected diseases.

PMID- 24670750
TI  - Immigration: Swiss science set to stay international.

PMID- 24670751
TI  - Biomedical research: Publish results from volunteer computing.

PMID- 24670752
TI  - Young scientists: Research problems in Portugal run deep.

PMID- 24670753
TI  - Sanitation: Thwart fatal infant gut parasite.

PMID- 24670754
TI  - Neuroscience: Updating views of visual updating.

PMID- 24670755
TI  - Solar System: Stranded in no-man's-land.

PMID- 24670756
TI  - Biogeochemistry: Methane minimalism.

PMID- 24670757
TI  - Climate science: A high bar for decadal forecasts of El Nino.

PMID- 24670758
TI  - Alzheimer's disease: A protective factor for the ageing brain.

PMID- 24670759
TI  - Low-temperature physics: Chaos in the cold.

PMID- 24670760
TI  - Osteoarthritis: The zinc link.

PMID- 24670761
TI  - The ultimate physical limits of privacy.
AB  - Among those who make a living from the science of secrecy, worry and paranoia are
      just signs of professionalism. Can we protect our secrets against those who wield
      superior technological powers? Can we trust those who provide us with tools for
      protection? Can we even trust ourselves, our own freedom of choice? Recent
      developments in quantum cryptography show that some of these questions can be
      addressed and discussed in precise and operational terms, suggesting that privacy
      is indeed possible under surprisingly weak assumptions. 

PMID- 24670762
TI  - REST and stress resistance in ageing and Alzheimer's disease.
AB  - Human neurons are functional over an entire lifetime, yet the mechanisms that
      preserve function and protect against neurodegeneration during ageing are
      unknown. Here we show that induction of the repressor element 1-silencing
      transcription factor (REST; also known as neuron-restrictive silencer factor,
      NRSF) is a universal feature of normal ageing in human cortical and hippocampal
      neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's
      disease. Chromatin immunoprecipitation with deep sequencing and expression
      analysis show that REST represses genes that promote cell death and Alzheimer's
      disease pathology, and induces the expression of stress response genes. Moreover,
      REST potently protects neurons from oxidative stress and amyloid beta-protein
      toxicity, and conditional deletion of REST in the mouse brain leads to age
      related neurodegeneration. A functional orthologue of REST, Caenorhabditis
      elegans SPR-4, also protects against oxidative stress and amyloid beta-protein
      toxicity. During normal ageing, REST is induced in part by cell non-autonomous
      Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and
      dementia with Lewy bodies, REST is lost from the nucleus and appears in
      autophagosomes together with pathological misfolded proteins. Finally, REST
      levels during ageing are closely correlated with cognitive preservation and
      longevity. Thus, the activation state of REST may distinguish neuroprotection
      from neurodegeneration in the ageing brain. 

PMID- 24670765
TI  - A Sedna-like body with a perihelion of 80 astronomical units.
AB  - The observable Solar System can be divided into three distinct regions: the rocky
      terrestrial planets including the asteroids at 0.39 to 4.2 astronomical units
      (AU) from the Sun (where 1 AU is the mean distance between Earth and the Sun),
      the gas giant planets at 5 to 30 AU from the Sun, and the icy Kuiper belt objects
      at 30 to 50 AU from the Sun. The 1,000-kilometre-diameter dwarf planet Sedna was
      discovered ten years ago and was unique in that its closest approach to the Sun
      (perihelion) is 76 AU, far greater than that of any other Solar System body.
      Formation models indicate that Sedna could be a link between the Kuiper belt
      objects and the hypothesized outer Oort cloud at around 10,000 AU from the Sun.
      Here we report the presence of a second Sedna-like object, 2012 VP113, whose
      perihelion is 80 AU. The detection of 2012 VP113 confirms that Sedna is not an
      isolated object; instead, both bodies may be members of the inner Oort cloud,
      whose objects could outnumber all other dynamically stable populations in the
      Solar System.

PMID- 24670766
TI  - Quantum chaos in ultracold collisions of gas-phase erbium atoms.
AB  - Atomic and molecular samples reduced to temperatures below one microkelvin, yet
      still in the gas phase, afford unprecedented energy resolution in probing and
      manipulating the interactions between their constituent particles. As a result of
      this resolution, atoms can be made to scatter resonantly on demand, through the
      precise control of a magnetic field. For simple atoms, such as alkalis,
      scattering resonances are extremely well characterized. However, ultracold
      physics is now poised to enter a new regime, where much more complex species can
      be cooled and studied, including magnetic lanthanide atoms and even molecules.
      For molecules, it has been speculated that a dense set of resonances in ultracold
      collision cross-sections will probably exhibit essentially random fluctuations,
      much as the observed energy spectra of nuclear scattering do. According to the
      Bohigas-Giannoni-Schmit conjecture, such fluctuations would imply chaotic
      dynamics of the underlying classical motion driving the collision. This would
      necessitate new ways of looking at the fundamental interactions in ultracold
      atomic and molecular systems, as well as perhaps new chaos-driven states of
      ultracold matter. Here we describe the experimental demonstration that random
      spectra are indeed found at ultralow temperatures. In the experiment, an
      ultracold gas of erbium atoms is shown to exhibit many Fano-Feshbach resonances,
      of the order of three per gauss for bosons. Analysis of their statistics verifies
      that their distribution of nearest-neighbour spacings is what one would expect
      from random matrix theory. The density and statistics of these resonances are
      explained by fully quantum mechanical scattering calculations that locate their
      origin in the anisotropy of the atoms' potential energy surface. Our results
      therefore reveal chaotic behaviour in the native interaction between ultracold
      atoms. 

PMID- 24670768
TI  - Geomagnetic fluctuations reveal stable stratification at the top of the Earth's
      core.
AB  - Modern observations of the geomagnetic field reveal fluctuations with a dominant
      period of about 60 years. These fluctuations are probably a result of waves in
      the liquid core, although the precise nature of the waves is uncertain. Common
      suggestions include a type of magnetic wave, known as a torsional oscillation,
      but recent studies favour periods that are too short to account for a 60-year
      fluctuation. Another possibility involves MAC waves, which arise from the
      interplay between magnetic, Archimedes and Coriolis forces. Waves with a suitable
      period can emerge when the top of the core is stably stratified. Here I show that
      MAC waves provide a good description of time-dependent zonal flow at the top of
      the core, as inferred from geomagnetic secular variation. The same wave motion
      can also account for unexplained fluctuations in the dipole field. Both of these
      independent predictions require a 140-kilometre-thick stratified layer with a
      buoyancy frequency comparable to the Earth's rotation rate. Such a stratified
      layer could have a thermal origin, implying a core heat flow of about 13
      terawatts. Alternatively, the layer could result from chemical stratification. In
      either case, the existence of a stratified layer at the top of the core obscures
      the nature of flow deeper in the core, where the magnetic field is continually
      regenerated. 

PMID- 24670767
TI  - Reconciliation of the carbon budget in the ocean's twilight zone.
AB  - Photosynthesis in the surface ocean produces approximately 100 gigatonnes of
      organic carbon per year, of which 5 to 15 per cent is exported to the deep ocean.
      The rate at which the sinking carbon is converted into carbon dioxide by
      heterotrophic organisms at depth is important in controlling oceanic carbon
      storage. It remains uncertain, however, to what extent surface ocean carbon
      supply meets the demand of water-column biota; the discrepancy between known
      carbon sources and sinks is as much as two orders of magnitude. Here we present
      field measurements, respiration rate estimates and a steady-state model that
      allow us to balance carbon sources and sinks to within observational
      uncertainties at the Porcupine Abyssal Plain site in the eastern North Atlantic
      Ocean. We find that prokaryotes are responsible for 70 to 92 per cent of the
      estimated remineralization in the twilight zone (depths of 50 to 1,000 metres)
      despite the fact that much of the organic carbon is exported in the form of
      large, fast-sinking particles accessible to larger zooplankton. We suggest that
      this occurs because zooplankton fragment and ingest half of the fast-sinking
      particles, of which more than 30 per cent may be released as suspended and slowly
      sinking matter, stimulating the deep-ocean microbial loop. The synergy between
      microbes and zooplankton in the twilight zone is important to our understanding
      of the processes controlling the oceanic carbon sink. 

PMID- 24670769
TI  - Methane fluxes show consistent temperature dependence across microbial to
      ecosystem scales.
AB  - Methane (CH4) is an important greenhouse gas because it has 25 times the global
      warming potential of carbon dioxide (CO2) by mass over a century. Recent
      calculations suggest that atmospheric CH4 emissions have been responsible for
      approximately 20% of Earth's warming since pre-industrial times. Understanding
      how CH4 emissions from ecosystems will respond to expected increases in global
      temperature is therefore fundamental to predicting whether the carbon cycle will
      mitigate or accelerate climate change. Methanogenesis is the terminal step in the
      remineralization of organic matter and is carried out by strictly anaerobic
      Archaea. Like most other forms of metabolism, methanogenesis is temperature
      dependent. However, it is not yet known how this physiological response combines
      with other biotic processes (for example, methanotrophy, substrate supply,
      microbial community composition) and abiotic processes (for example, water-table
      depth) to determine the temperature dependence of ecosystem-level CH4 emissions.
      It is also not known whether CH4 emissions at the ecosystem level have a
      fundamentally different temperature dependence than other key fluxes in the
      carbon cycle, such as photosynthesis and respiration. Here we use meta-analyses
      to show that seasonal variations in CH4 emissions from a wide range of ecosystems
      exhibit an average temperature dependence similar to that of CH4 production
      derived from pure cultures of methanogens and anaerobic microbial communities.
      This average temperature dependence (0.96 electron volts (eV)), which corresponds
      to a 57-fold increase between 0 and 30 degrees C, is considerably higher than
      previously observed for respiration (approximately 0.65 eV) and photosynthesis
      (approximately 0.3 eV). As a result, we show that both the emission of CH4 and
      the ratio of CH4 to CO2 emissions increase markedly with seasonal increases in
      temperature. Our findings suggest that global warming may have a large impact on
      the relative contributions of CO2 and CH4 to total greenhouse gas emissions from
      aquatic ecosystems, terrestrial wetlands and rice paddies. 

PMID- 24670764
TI  - A promoter-level mammalian expression atlas.
AB  - Regulated transcription controls the diversity, developmental pathways and
      spatial organization of the hundreds of cell types that make up a mammal. Using
      single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and
      their usage in human and mouse primary cells, cell lines and tissues to produce a
      comprehensive overview of mammalian gene expression across the human body. We
      find that few genes are truly 'housekeeping', whereas many mammalian promoters
      are composite entities composed of several closely separated TSSs, with
      independent cell-type-specific expression profiles. TSSs specific to different
      cell types evolve at different rates, whereas promoters of broadly expressed
      genes are the most conserved. Promoter-based expression analysis reveals key
      transcription factors defining cell states and links them to binding-site motifs.
      The functions of identified novel transcripts can be predicted by coexpression
      and sample ontology enrichment analyses. The functional annotation of the
      mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles
      and functional annotation of mammalian cell-type-specific transcriptomes with
      wide applications in biomedical research. 

PMID- 24670763
TI  - An atlas of active enhancers across human cell types and tissues.
AB  - Enhancers control the correct temporal and cell-type-specific activation of gene
      expression in multicellular eukaryotes. Knowing their properties, regulatory
      activity and targets is crucial to understand the regulation of differentiation
      and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority
      of human tissues and cell types, to produce an atlas of active, in vivo
      transcribed enhancers. We show that enhancers share properties with CpG-poor
      messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively
      short unspliced RNAs, the generation of which is strongly related to enhancer
      activity. The atlas is used to compare regulatory programs between different
      cells at unprecedented depth, to identify disease-associated regulatory single
      nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous
      enhancers. We further explore the utility of enhancer redundancy, which explains
      gene expression strength rather than expression patterns. The online FANTOM5
      enhancer atlas represents a unique resource for studies on cell-type-specific
      enhancers and gene regulation. 

PMID- 24670770
TI  - A suspension-feeding anomalocarid from the Early Cambrian.
AB  - Large, actively swimming suspension feeders evolved several times in Earth's
      history, arising independently from groups as diverse as sharks, rays and stem
      teleost fishes, and in mysticete whales. However, animals occupying this niche
      have not been identified from the early Palaeozoic era. Anomalocarids, a group of
      stem arthropods that were the largest nektonic animals of the Cambrian and
      Ordovician periods, are generally thought to have been apex predators. Here we
      describe new material from Tamisiocaris borealis, an anomalocarid from the Early
      Cambrian (Series 2) Sirius Passet Fauna of North Greenland, and propose that its
      frontal appendage is specialized for suspension feeding. The appendage bears
      long, slender and equally spaced ventral spines furnished with dense rows of long
      and fine auxiliary spines. This suggests that T. borealis was a microphagous
      suspension feeder, using its appendages for sweep-net capture of food items down
      to 0.5 mm, within the size range of mesozooplankton such as copepods. Our
      observations demonstrate that large, nektonic suspension feeders first evolved
      during the Cambrian explosion, as part of an adaptive radiation of anomalocarids.
      The presence of nektonic suspension feeders in the Early Cambrian, together with
      evidence for a diverse pelagic community containing phytoplankton and
      mesozooplankton, indicate the existence of a complex pelagic ecosystem supported
      by high primary productivity and nutrient flux. Cambrian pelagic ecosystems seem
      to have been more modern than previously believed. 

PMID- 24670771
TI  - Visual space is compressed in prefrontal cortex before eye movements.
AB  - We experience the visual world through a series of saccadic eye movements, each
      one shifting our gaze to bring objects of interest to the fovea for further
      processing. Although such movements lead to frequent and substantial
      displacements of the retinal image, these displacements go unnoticed. It is
      widely assumed that a primary mechanism underlying this apparent stability is an
      anticipatory shifting of visual receptive fields (RFs) from their presaccadic to
      their postsaccadic locations before movement onset. Evidence of this predictive
      'remapping' of RFs has been particularly apparent within brain structures
      involved in gaze control. However, critically absent among that evidence are
      detailed measurements of visual RFs before movement onset. Here we show that
      during saccade preparation, rather than remap, RFs of neurons in a prefrontal
      gaze control area massively converge towards the saccadic target. We mapped the
      visual RFs of prefrontal neurons during stable fixation and immediately before
      the onset of eye movements, using multi-electrode recordings in monkeys.
      Following movements from an initial fixation point to a target, RFs remained
      stationary in retinocentric space. However, in the period immediately before
      movement onset, RFs shifted by as much as 18 degrees of visual angle, and
      converged towards the target location. This convergence resulted in a threefold
      increase in the proportion of RFs responding to stimuli near the target region.
      In addition, like in human observers, the population of prefrontal neurons
      grossly mislocalized presaccadic stimuli as being closer to the target. Our
      results show that RF shifts do not predict the retinal displacements due to
      saccades, but instead reflect the overriding perception of target space during
      eye movements. 

PMID- 24670773
TI  - Selective reduction of afterload in right heart assist therapy: a mock loop
      study?.
AB  - OBJECTIVES: The treatment of right ventricular failure is closely linked to
      effects on pulmonary vascular resistance and thus the right ventricular (RV)
      afterload. Medical therapy includes afterload-decreasing drugs such as nitric
      oxide and prostacycline. However, current devices for mechanical unloading of the
      right ventricle aim at a decrease in preload increasing the pulmonary volume
      loading. In our concept study, we tested a minimally invasive right ventricular
      assist device (MIRVAD) that specifically reduces the afterload. METHODS: The
      MIRVAD is supposed to be a foldable device for temporary transvascular placement
      in the pulmonary artery. We incorporated a MIRVAD prototype into a mock
      circulatory loop that can reproduce haemodynamic interaction between the pump and
      the physiological system. Pulmonary hypertension (PH), right heart failure (RHF)
      and MIRVAD-assisted cases were simulated. The key haemodynamic parameters for RV
      unloading were recorded. RESULTS: Mock loop simulation attested to a sufficient
      right ventricular unloading by serial application of a miniaturized impeller pump
      in the pulmonary artery. The afterload, represented by the pulmonary arterial
      root pressure, was recovered to the healthy range (32.62-10.93 mmHg) for the
      simulated PH case. In the simulated RHF case, the impaired pulmonary perfusion
      increased from 43.4 to 88.8% of the healthy level and the total ventricular work
      reduced from 0.381 to 0.197 J at a pump speed of 3500 rpm. At pump speeds higher
      than 3500 rpm, the pulmonary valve remains constantly open and the right
      ventricular configuration changes into a simple perfused hollow body.
      CONCLUSIONS: The feasibility of RV unloading by a selective decrease in RV
      afterload was proved in principle. By alternation of the pump speed, gradual
      reloading in sense of a myocardial training may be achieved. The results will be
      validated by future animal trials where the relationship between the level of
      support and pulmonary vascular pressure can be investigated in vivo. Further
      device design concerning foldable impeller leaflets will be carried out. At a
      final stage, the crimped version is supposed to reach a size below 1 cm to
      facilitate minimally invasive insertion.

PMID- 24670774
TI  - Timing of urinary catheter removal after uncomplicated total abdominal
      hysterectomy: a prospective randomized trial.
AB  - OBJECTIVE: To assess whether immediate (0h), intermediate (after 6h) or delayed
      (after 24h) removal of an indwelling urinary catheter after uncomplicated
      abdominal hysterectomy can affect the rate of re-catheterization due to urinary
      retention, rate of urinary tract infection, ambulation time and length of
      hospital stay. STUDY DESIGN: Prospective randomized controlled trial conducted at
      Suez Canal University Hospital, Egypt. Two hundred and twenty-one women underwent
      total abdominal hysterectomy for benign gynecological diseases and were randomly
      allocated into three groups. Women in group A (73 patients) had their urinary
      catheter removed immediately after surgery. Group B (81 patients) had the
      catheter removed 6h post-operatively while in group C (67 patients) the catheter
      was removed after 24h. The main outcome measures were the frequency of urinary
      retention, urinary tract infections, ambulation time and length of hospital stay.
      RESULTS: There was a significantly higher number of urinary retention episodes
      requiring re-catheterization in the immediate removal group compared to the
      intermediate and delayed removal groups (16.4% versus 2.5% and 0% respectively).
      Delayed urinary catheter removal was associated with a higher incidence of
      urinary tract infections (15%), delayed ambulation time (10.3h) and longer
      hospital stay (5.6 days) compared to the early (1.4%, 4.1h and 3.2 days
      respectively) and intermediate (3.7%, 6.8h and 3.4 days respectively) removal
      groups. CONCLUSIONS: Removal of the urinary catheter 6h postoperatively appears
      to be more advantageous than early or late removal in cases of uncomplicated
      total abdominal hysterectomy.

PMID- 24670776
TI  - Childhood and maternal effects on physical health related quality of life five
      decades later: the British 1946 birth cohort.
AB  - Limited research has been done on the relationships between childhood factors and
      adult physical health related quality of life, with the underlying pathways not
      fully elucidated. Data from 2292 participants of the British 1946 birth cohort
      were used to examine the relationship of childhood characteristics and family
      environment with principal component summary (PCS) scores and the physical
      functioning (PF) subscale of the SF-36 at age 60-64 years. Impaired physical
      functioning was defined as the lowest quartile scores in the PF subscale.
      Childhood factors (father in manual social class versus non-manual (beta =  
      2.34; 95%CI: -3.39, -1.28) and poor maternal health versus good/excellent
      maternal health (beta =  -6.18; -8.78, -3.57)) were associated with lower PCS
      scores at 60-64 years. Adult health behaviours (increasing BMI, lifelong smoking,
      and lower physical activity) at 53 years were identified as strong risk factors
      for lower PCS scores. After adjusting for these factors and education level (N =
      1463), only poor maternal health remained unattenuated (beta =  -5.07; -7.62, 
      2.51). Similarly poor maternal health doubled the risk of reporting impaired PF
      (Odds ratio =  2.45; 95%CI: 1.39, 4.30); serious illness in childhood (OR = 1.44;
      1.01, 2.06) and lower educational level attained were also risk factors for
      impaired PF (N = 1526). While findings suggest the influence of father's social
      class on physical health related quality of life are mediated by modifiable adult
      social factors and health behaviours; health professionals should also be mindful
      of the inter-generational risk posed by poor maternal health on the physical
      health related quality of life of her offspring almost five decades later. 

PMID- 24670777
TI  - Combinatorial discovery through a distributed outreach program: investigation of
      the photoelectrolysis activity of p-type Fe, Cr, Al oxides.
AB  - We report the identification of a semiconducting p-type oxide containing iron,
      aluminum, and chromium (Fe2-x-yCrxAlyO3) with previously unreported
      photoelectrolysis activity that was discovered by an undergraduate scientist
      participating in the Solar Hydrogen Activity research Kit (SHArK) program. The
      SHArK program is a distributed combinatorial science outreach program designed to
      provide a simple and inexpensive way for high school and undergraduate students
      to participate in the search for metal oxide materials that are active for the
      photoelectrolysis of water. The identified Fe2-x-yCrxAlyO3 photoelectrolysis
      material possesses many properties that make it a promising candidate for further
      optimization for potential application in a photoelectrolysis device. In addition
      to being composed of earth abundant elements, the FeCrAl oxide material has a
      band gap of 1.8 eV. Current-potential measurements for Fe2-x-yCrxAlyO3 showed an
      open circuit photovoltage of nearly 1 V; however, the absorbed photon conversion
      efficiency for hydrogen evolution was low (2.4 * 10(-4) at 530 nm) albeit without
      any deposited hydrogen evolution catalyst. X-ray diffraction of the pyrolyzed
      polycrystalline thin Fe2-x-yCrxAlyO3 film on fluorine-doped tin oxide substrates
      shows a hexagonal phase (hematite structure) and scanning electron microscope
      images show morphology consisting of small crystallites. 

PMID- 24670775
TI  - A novel artificial microRNA expressing AAV vector for phospholamban silencing in
      cardiomyocytes improves Ca2+ uptake into the sarcoplasmic reticulum.
AB  - In failing rat hearts, post-transcriptonal inhibition of phospholamban (PLB)
      expression by AAV9 vector-mediated cardiac delivery of short hairpin RNAs
      directed against PLB (shPLBr) improves both impaired SERCA2a controlled Ca2+
      cycling and contractile dysfunction. Cardiac delivery of shPLB, however, was
      reported to cause cardiac toxicity in canines. Thus we developed a new AAV
      vector, scAAV6-amiR155-PLBr, expressing a novel engineered artificial microRNA
      (amiR155-PLBr) directed against PLB under control of a heart-specific hybrid
      promoter. Its PLB silencing efficiency and safety were compared with those of an
      AAV vector expressing shPLBr (scAAV6-shPLBr) from an ubiquitously active U6
      promoter. Investigations were carried out in cultured neonatal rat cardiomyocytes
      (CM) over a period of 14 days. Compared to shPLBr, amiR155-PLBr was expressed at
      a significantly lower level, resulting in delayed and less pronounced PLB
      silencing. Despite decreased knockdown efficiency of scAAV6-amiR155-PLBr, a
      similar increase of the SERCA2a-catalyzed Ca2+ uptake into sarcoplasmic reticulum
      (SR) vesicles was observed for both the shPLBr and amiR155-PLBr vectors.
      Proteomic analysis confirmed PLB silencing of both therapeutic vectors and
      revealed that shPLBr, but not the amiR155-PLBr vector, increased the
      proinflammatory proteins STAT3, STAT1 and activated STAT1 phosphorylation at the
      key amino acid residue Tyr701. Quantitative RT-PCR analysis detected alterations
      in the expression of several cardiac microRNAs after treatment of CM with scAAV6
      shPLBr and scAAV6-amiR155-PLBr, as well as after treatment with its related
      amiR155- and shRNAs-expressing control AAV vectors. The results demonstrate that
      scAAV6-amiR155-PLBr is capable of enhancing the Ca2+ transport function of the
      cardiac SR PLB/SERCA2a system as efficiently as scAAV6-shPLBr while offering a
      superior safety profile. 

PMID- 24670778
TI  - IGF-1 gene expression is differentially regulated by estrogen receptors alpha and
      beta in mouse endometrial stromal cells and ovarian granulosa cells.
AB  - Insulin-like growth factor 1 (IGF-1) is involved in regulations of reproductive
      functions in rats and mice. IGF-1 expression is regulated by estrogen in several
      reproductive organs including the uterus and ovary. Two types of estrogen
      receptor (ERalpha and ERbeta) are expressed in mouse uteri and ovaries, and it is
      unclear whether they differently mediate IGF-1 gene transcription. To clarify the
      roles of ERalpha and ERbeta, mouse endometrial stromal cells and ovarian
      granulosa cells were treated with ligands specific for individual estrogen
      receptors. In endometrial stromal cells, propyl-pyrazole-triol (PPT; ERalpha
      selective agonist) increased Igf1 mRNA expression, which was suppressed by methyl
      piperidino-pyrazole (MPP, ERalpha-selective antagonist), while
      diarylpropionitrile (DPN, ERbeta-potency selective agonist) increased Igf1 mRNA
      expression, which was inhibited by MPP but not by 4-[2-phenyl-5,7
      bis(trifluoromethyl)pyrazolo[1,5-alpha]pyrimidin-3-yl]phenol (PHTPP; ERbeta
      antagonist). PHTPP enhanced the DPN-induced increase in Igf1 mRNA expression. In
      ovarian granulosa cells, E2 and DPN decreased Igf1 mRNA expression, whereas PPT
      did not affect Igf1 mRNA levels. In these cells, PHTPP inhibited the DPN-induced
      decrease in Igf1 mRNA expression. These results suggest that ERalpha facilitates
      Igf1 transcription, whereas ERbeta appears to inhibit Igf1 gene transcription in
      mouse endometrial stromal cells and ovarian granulosa cells. 

PMID- 24670779
TI  - Fabrication of polymer nanowires via maskless O2 plasma etching.
AB  - In this paper, we introduce a simple fabrication technique which can pattern high
      aspect-ratio polymer nanowire structures of photoresist films by using a maskless
      one-step oxygen plasma etching process. When carbon-based photoresist materials
      on silicon substrates are etched by oxygen plasma in a metallic etching chamber,
      nanoparticles such as antimony, aluminum, fluorine, silicon or their compound
      materials are self-generated and densely occupy the photoresist polymer surface.
      Such self-masking effects result in the formation of high-aspect-ratio vertical
      nanowire arrays of the polymer in the reactive ion etching mode without the
      necessity of any artificial etch mask. Nanowires fabricated by this technique
      have a diameter of less than 50 nm and an aspect ratio greater than 20. When such
      nanowires are fabricated on lithographically pre-patterned photoresist films,
      hierarchical and hybrid nanostructures of polymer are also conveniently attained.
      This simple and high-throughput fabrication technique for polymer nanostructures
      should pave the way to a wide range of applications such as in sensors, energy
      storage, optical devices and microfluidics systems. 

PMID- 24670782
TI  - Health care in turmoil.

PMID- 24670781
TI  - Active transport of vesicles in neurons is modulated by mechanical tension.
AB  - Effective intracellular transport of proteins and organelles is critical in
      cells, and is especially important for ensuring proper neuron functionality. In
      neurons, most proteins are synthesized in the cell body and must be transported
      through thin structures over long distances where normal diffusion is
      insufficient. Neurons transport subcellular cargo along axons and neurites
      through a stochastic interplay of active and passive transport. Mechanical
      tension is critical in maintaining proper function in neurons, but its role in
      transport is not well understood. To this end, we investigate the active and
      passive transport of vesicles in Aplysia neurons while changing neurite tension
      via applied strain, and quantify the resulting dynamics. We found that tension in
      neurons modulates active transport of vesicles by increasing the probability of
      active motion, effective diffusivity, and induces a retrograde bias. We show that
      mechanical tension modulates active transport processes in neurons and that
      external forces can couple to internal (subcellular) forces and change the
      overall transport dynamics. 

PMID- 24670783
TI  - Blood-brain barrier transport pathways for cytoprotective thiols.
AB  - The purpose of this study is to further define transport pathways for biological
      thiols by blood-brain barrier (BBB) endothelial cells, as a means of identifying
      endogenous cytoprotective mechanisms and potential therapeutic protocols for
      oxidative injury. Similar low-affininty, high-capacity passive carriers for
      glutathione (GSH) were observed at both the luminal (blood-facing) and abluminal
      (brain-facing) plasma membranes of BBB endothelial cells. These carriers are
      voltage dependent, favoring outward movement of intact peptide across both
      membrane domains, including efflux at the luminal plasmalemma where gamma
      glutamyl transpeptidase is located. Although present at both cell surfaces, the
      carriers are distributed unequally, with more appearing in the abluminal
      membrane. By contrast, high-affinity, low-capacity sodium-dependent GSH
      cotransport (Na-GSH) is observed only at the abluminal membrane, indicative of an
      inwardly directed active peptide carrier at the brain-facing plasma membrane.
      Treatment of cultured BBB endothelial cells with the GSH precursor gamma-glutamyl
      cysteine reduces cell damage under conditions simulating ischemia and
      reperfusion. These findings are consistent with the presence of (1) a typical
      gamma-glutamyl cycle at the luminal membrane of BBB endothelial cells, (2) a
      significant efflux pathway at the abluminal membrane allowing passive movement of
      BBB GSH into brain extracellular fluid, (3) a Na-dependent, brain-to-blood
      pathway for transcellular transport of GSH, and (4) a mechanism for
      cytoprotection by gamma-glutamyl cysteine, under conditions of ischemia and
      reperfusion. 

PMID- 24670785
TI  - For OVS, Spring has sprung.

PMID- 24670784
TI  - Effectiveness of family planning policies: the abortion paradox.
AB  - OBJECTIVE: The relation between levels of contraceptive use and the incidence of
      induced abortion remains a topic of heated debate. Many of the contradictions are
      likely due to the fact that abortion is the end point of a process that starts
      with sexual activity, contraceptive use (or non-use), followed by unwanted
      pregnancy, a decision to terminate, and access to abortion. Trends in abortion
      rates reflect changes in each step of this process, and opposing trends may
      cancel each other out. This paper aims to investigate the roles played by the
      dissemination of contraception and the evolving norms of motherhood on changes in
      abortion rates. METHODS: Drawing data from six national probability surveys that
      explored contraception and pregnancy wantedness in France from 1978 through 2010,
      we used multivariate linear regression to explore the associations between trends
      in contraceptive rates and trends in (i) abortion rates, (ii) unwanted pregnancy
      rates, (iii) and unwanted birth rates, and to determine which of these 3
      associations was strongest. FINDINGS: The association between contraceptive rates
      and abortion rates over time was weaker than that between contraception rates and
      unwanted pregnancy rates (p = 0.003). Similarly, the association between
      contraceptive rates and unwanted birth rates over time was weaker than that
      between contraceptive rates and unwanted pregnancy rates (p = 0.000).

PMID- 24670787
TI  - Removals of phenolic compounds and phthalic acid esters in landfill leachate by
      microbial sludge of two-stage membrane bioreactor.
AB  - Removals of bisphenol A (BPA), 2,6-di-tert-butylphenol (2,6-DTBP), 2,6-di-tert
      butyl-4methylphenol (BHT), di-ethyl phthalate (DEP), di-butyl phthalate (DBP) and
      bis (2-ethylhexyl) phthalate (DEHP) were monitored in two-stage membrane
      bioreactor (MBR) by operating under no sludge wastage condition for 500 days.
      Those emerging contaminants were removed by 99.5%, 99.0%, 99.5%, 97.9%, 96.8% and
      95.7% under long term operation in MBR without reaching maximum adsorption
      capacity of sludge. Biodegradation was the main mechanism for their removals in
      MBR systems and the microbial activities were enhanced by long sludge age
      operating condition. The removals of those compounds by microbial sludge in MBR
      by adsorption and combined (adsorption & biodegradation) mechanisms were well
      explained by pseudo-second order and first order kinetics, respectively. 

PMID- 24670788
TI  - Transcatheter aortic valve and valve-in-valve implantation in a beating stenotic
      porcine aortic valve: intracardiac endoscopic view?.

PMID- 24670789
TI  - Carbonic anhydrase activation is associated with worsened pathological remodeling
      in human ischemic diabetic cardiomyopathy.
AB  - BACKGROUND: Diabetes mellitus (DM) has multifactorial detrimental effects on
      myocardial tissue. Recently, carbonic anhydrases (CAs) have been shown to play a
      major role in diabetic microangiopathy but their role in the diabetic
      cardiomyopathy is still unknown. METHODS AND RESULTS: We obtained left
      ventricular samples from patients with DM type 2 (DM-T2) and nondiabetic (NDM)
      patients with postinfarct heart failure who were undergoing surgical coronary
      revascularization. Myocardial levels of CA-I and CA-II were 6- and 11-fold
      higher, respectively, in DM-T2 versus NDM patients. Elevated CA-I expression was
      mainly localized in the cardiac interstitium and endothelial cells. CA-I induced
      by high glucose levels hampers endothelial cell permeability and determines
      endothelial cell apoptosis in vitro. Accordingly, capillary density was
      significantly lower in the DM-T2 myocardial samples (mean+/-SE=2152+/-146 versus
      4545+/-211/mm(2)). On the other hand, CA-II was mainly upregulated in
      cardiomyocytes. The latter was associated with sodium-hydrogen exchanger-1
      hyperphosphorylation, exaggerated myocyte hypertrophy (cross-sectional area 565+/
      34 versus 412+/-27 MUm(2)), and apoptotic death (830+/-54 versus 470+/-34 per
      10(6) myocytes) in DM-T2 versus NDM patients. CA-II is activated by high glucose
      levels and directly induces cardiomyocyte hypertrophy and death in vitro, which
      are prevented by sodium-hydrogen exchanger-1 inhibition. CA-II was shown to be a
      direct target for repression by microRNA-23b, which was downregulated in
      myocardial samples from DM-T2 patients. MicroRNA-23b is regulated by p38 mitogen
      activated protein kinase, and it modulates high-glucose CA-II-dependent effects
      on cardiomyocyte survival in vitro. CONCLUSIONS: Myocardial CA activation is
      significantly elevated in human diabetic ischemic cardiomyopathy. These data may
      open new avenues for targeted treatment of diabetic heart failure.

PMID- 24670790
TI  - Elastic anisotropy of experimental analogues of perovskite and post-perovskite
      help to interpret D'' diversity.
AB  - Recent studies show that the D'' layer, just above the Earth's core-mantle
      boundary, is composed of MgSiO3 post-perovskite and has significant lateral
      inhomogeneity. Here we consider the D'' diversity as related to the single
      crystal elasticity of the post-perovskite phase. We measure the single-crystal
      elasticity of the perovskite Pbnm-CaIrO3 and post-perovskite Cmcm-CaIrO3 using
      inelastic X-ray scattering. These materials are structural analogues to same
      phases of MgSiO3. Our results show that Cmcm-CaIrO3 is much more elastically
      anisotropic than Pbnm-CaIrO3, which offers an explanation for the enigmatic
      seismic wave velocity jump at the D'' discontinuity. Considering the relation
      between lattice preferred orientation and seismic anisotropy in the D'' layer, we
      suggest that the c axis of post-perovskite MgSiO3 aligns vertically beneath the
      Circum-Pacific rim, and the b axis vertically beneath the Central Pacific. 

PMID- 24670791
TI  - Exercise prevents weight gain and alters the gut microbiota in a mouse model of
      high fat diet-induced obesity.
AB  - BACKGROUND: Diet-induced obesity (DIO) is a significant health concern which has
      been linked to structural and functional changes in the gut microbiota. Exercise
      (Ex) is effective in preventing obesity, but whether Ex alters the gut microbiota
      during development with high fat (HF) feeding is unknown. OBJECTIVE: Determine
      the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and
      in HF-DIO. METHODS: Male C57BL/6 littermates (5 weeks) were distributed equally
      into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice
      were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and
      odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12
      weeks and used for bacterial DNA isolation. DNA was subjected both to
      quantitative PCR using primers specific to the 16S rRNA encoding genes for
      Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification
      using the Illumina MiSeq platform. Data were analyzed using a one or two-way
      ANOVA or Pearson correlation. RESULTS: HF diet resulted in significantly greater
      body weight and adiposity as well as decreased glucose tolerance that were
      prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with
      principal coordinates analysis indicated clustering by both diet and Ex at week
      12. Sequencing demonstrated Ex-induced changes in the percentage of major
      bacterial phyla at 12 weeks. A correlation between total Ex distance and the
      DeltaCt Bacteroidetes: DeltaCt Firmicutes ratio from qPCR demonstrated a
      significant inverse correlation (r2 = 0.35, p = 0.043). CONCLUSION: Ex induces a
      unique shift in the gut microbiota that is different from dietary effects.
      Microbiota changes may play a role in Ex prevention of HF-DIO.

PMID- 24670792
TI  - Down-regulation of heat shock protein HSP90ab1 in radiation-damaged lung cells
      other than mast cells.
AB  - Ionizing radiation (IR) leads to fibrosing alveolitis (FA) after a lag period of
      several weeks to months. In a rat model, FA starts at 8 weeks after IR. Before
      that, at 5.5 weeks after IR, the transcription factors Sp1 (stimulating protein
      1) and AP-1 (activator protein 1) are inactivated. To find genes/proteins that
      were down-regulated at that time, differentially expressed genes were identified
      in a subtractive cDNA library and verified by quantitative RT-PCR (reverse
      transcriptase polymerase chain reaction), western blotting and
      immunohistochemistry (IH). The mRNA of the molecular chaperone HSP90AB1 (heat
      shock protein 90 kDa alpha, class B member 1) was down-regulated 5.5 weeks after
      IR. Later, when FA manifested, HSP90ab1 protein was down-regulated by more than
      90% in lung cells with the exception of mast cells. In most mast cells of the
      normal lung, both HSP90ab1 and HSP70, another major HSP, show a very low level of
      expression. HSP70 was massively up-regulated in all mast cells three months after
      irradiation whereas HSP90AB1 was up-regulated only in a portion of mast cells.
      The strong changes in the expression of central molecular chaperones may
      contribute to the well-known disturbance of cellular functions in radiation
      damaged lung tissue. 

PMID- 24670793
TI  - Marginal Zone Macrophage Receptor MARCO Is Trapped in Conduits Formed by
      Follicular Dendritic Cells in the Spleen.
AB  - The marginal zone (MZ) region of the spleen plays an important role in leukocyte
      traffic and the removal of blood-borne pathogens by resident macrophages.
      Macrophage receptor with a collagenous structure (MARCO), expressed by MZ
      macrophages, recognizes several microbial ligands and is also involved in the
      retention of MZ B cells. Here, we report that MARCO is also associated with
      follicular dendritic cells (FDCs) in the spleen. In its FDC-associated form MARCO
      is arranged in 0.3-0.5-MUm diameter granular-fibrillar structures with an
      appearance similar to the white pulp conduit system formed by fibroblastic
      reticular cells (FRCs), but with different compartment preference. The follicular
      display of MARCO resists irradiation and requires the presence of both MZ
      macrophages and differentiated FDCs. The follicular delivery of MARCO is
      independent from the shuffling of marginal zone B cells, and it persists after
      clodronate liposome-mediated depletion of MZ macrophages. Our findings thus
      indicate that MARCO is distributed to both MZ and follicles within the spleen
      into conduit-like structures, where FDC-bound MARCO may mediate communication
      between the stromal microenvironments of MZ and follicles.

PMID- 24670794
TI  - Characterization of Endoneurial Fibroblast-like Cells from Human and Rat
      Peripheral Nerves.
AB  - Endoneurial fibroblast-like cells (EFLCs) are one of the cell populations present
      in the peripheral nervous system. The role and immunophenotypic characteristics
      of EFLCs are not well known and led us to perform a histological and cytological
      study of EFLCs in normal human and rat peripheral nerves. We found that all EFLCs
      express CD34, neural/glial antigen 2 (NG2), and prolyl-4-hydrolase-beta. In
      addition, half of the EFLCs in normal peripheral nerves express platelet-derived
      growth factor receptor-beta (PDGFR-beta) and some also express the intermediate
      filament nestin in vivo (at a lower level than Schwann cells, which express high
      levels of nestin). Using cell cultures of purified EFLCs, we characterized
      subpopulations of EFLCs expressing PDGFR-beta alone or PDGFR-beta and nestin.
      Experimental nerve lesions in rat resulted in an increase in nestin-positive
      EFLCs, which returned to normal levels after 8 days. This suggests that some
      EFLCs could have a different proliferative and/or regenerative potential than
      others, and these EFLCs may play a role in the initial phase of nerve repair.
      These "activated" EFLCs share some immunophenotypic similarities with pericytes
      and Interstitial cells of Cajal, which have progenitor cell potentials. This
      raises the questions as to whether a proportion of EFLCs have a possible role as
      endoneurial progenitor cells.

PMID- 24670795
TI  - Human Eosinophil Leukocytes Express Protein Disulfide Isomerase in Secretory
      Granules and Vesicles: Ultrastructural Studies.
AB  - Protein disulfide isomerase (PDI) has fundamental roles in the oxidative folding
      of proteins in the endoplasmic reticulum (ER) of eukaryotic cells. The study of
      this molecule has been attracting considerable attention due to its association
      with other cell functions and human diseases. In leukocytes, such as neutrophils,
      PDI is involved with cell adhesion, signaling and inflammation. However, the
      expression of PDI in other leukocytes, such as eosinophils, important cells in
      inflammatory, allergic and immunomodulatory responses, remains to be defined.
      Here we used different approaches to investigate PDI expression within human
      eosinophils. Western blotting and flow cytometry demonstrated high PDI expression
      in both unstimulated and CCL11/eotaxin-1-stimulated eosinophils, with similar
      levels in both conditions. By using an immunogold electron microscopy technique
      that combines better epitope preservation and secondary Fab-fragments of
      antibodies linked to 1.4-nm gold particles for optimal access to microdomains, we
      identified different intracellular sites for PDI. In addition to predictable
      strong PDI labeling at the nuclear envelope, other unanticipated sites, such as
      secretory granules, lipid bodies and vesicles, including large transport vesicles
      (eosinophil sombrero vesicles), were also labeled. Thus, we provide the first
      identification of PDI in human eosinophils, suggesting that this molecule may
      have additional/specific functions in these leukocytes.

PMID- 24670796
TI  - Validating Antibodies to the Cannabinoid CB2 Receptor: Antibody Sensitivity Is
      Not Evidence of Antibody Specificity.
AB  - Antibody-based methods for the detection and quantification of membrane integral
      proteins, in particular, the G protein-coupled receptors (GPCRs), have been
      plagued with issues of primary antibody specificity. In this report, we
      investigate one of the most commonly utilized commercial antibodies for the
      cannabinoid CB2 receptor, a GPCR, using immunoblotting in combination with mass
      spectrometry. In this way, we were able to develop powerful negative and novel
      positive controls. By doing this, we are able to demonstrate that it is possible
      for an antibody to be sensitive for a protein of interest-in this case CB2-but
      still cross-react with other proteins and therefore lack specificity.
      Specifically, we were able to use western blotting combined with mass
      spectrometry to unequivocally identify CB2 protein in over-expressing cell lines.
      This shows that a common practice of validating antibodies with positive controls
      only is insufficient to ensure antibody reliability. In addition, our work is the
      first to develop a label-free method of protein detection using mass spectrometry
      that, with further refinement, could provide unequivocal identification of CB2
      receptor protein in native tissues.

PMID- 24670797
TI  - A critical role for thymic stromal lymphopoietin in nickel-induced allergy in
      mice.
AB  - Ni is the most frequent cause of contact allergy induced by metals. However, the
      underlying mechanism of this induction is unknown. Our previous research
      demonstrates that activation of dendritic cells (DCs) through p38MAPK/MKK6 is
      required for Ni-induced allergy in mice. In the current study, we investigated
      the cellular and molecular mechanisms underlying Ni-induced allergy using a mouse
      model that involves injecting Ni into the ear, with or without Freund's
      incomplete or complete adjuvants. Nickel had greater potential to cause allergic
      reactions compared with palladium and gold. Among the proteins expressed at
      higher levels in mice with Ni-induced allergy, we focused on thymic stromal
      lymphopoietin (TSLP), which is produced in abundance by keratinocytes. We
      detected increased expression of the TSLP receptor (TSLPR) in DCs from cervical
      lymph nodes of mice with Ni-induced allergy, suggesting that DCs in ear tissues
      were activated through TSLPR signaling induced by keratinocyte-derived TSLP.
      Furthermore, delayed-type hypersensitivity reactions in mice with Ni-induced
      allergy were decreased significantly by injection of a Tslp-short interfering RNA
      along with atelocollagen in the ear skin. These results suggest that Ni allergy
      may be triggered by a TSLP/TSLPR-mediated interaction between epithelial and
      immune cells. 

PMID- 24670798
TI  - Congenital heart disease linked to maternal autoimmunity against cardiac myosin.
AB  - Structural congenital heart disease (CHD) has not previously been linked to
      autoimmunity. In our study, we developed an autoimmune model of structural CHD
      that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD
      primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant
      autoantigen in autoimmune heart disease, we hypothesized that immunization with
      CM might lead to transplacental passage of maternal autoantibodies and a prenatal
      HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal
      and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated
      with structural CHD that included diminished left ventricular cavity dimensions
      in the affected progeny. Further, fetuses that developed a marked HLHS phenotype
      had elevated serum titers of anti-beta-adrenergic receptor Abs, as well as
      increased protein kinase A activity, suggesting a potential mechanism for the
      observed pathological changes. Our maternal-fetal model presents a new concept
      linking autoimmunity against CM and cardiomyocyte proliferation with cardinal
      features of HLHS. To our knowledge, this report shows the first evidence in
      support of a novel immune-mediated mechanism for pathogenesis of structural CHD
      that may have implications in its future diagnosis and treatment. 

PMID- 24670799
TI  - Synergistic therapeutic vascular cytoprotection against complement-mediated
      injury induced via a PKCalpha-, AMPK-, and CREB-dependent pathway.
AB  - Endothelial injury and dysfunction precede accelerated arterial disease in
      allograft vasculopathy and systemic autoimmune diseases and involve pathogenic
      Abs and complement. Recent reports suggest that switching to rapamycin from
      calcineurin antagonists reduces posttransplant vasculopathy and prolongs survival
      following cardiac transplantion. The majority of these patients also receive
      statin therapy. We examined potential mechanisms underlying this protective
      response in human endothelial cells and identified synergy between rapamycin and
      atorvastatin. Mechanistically, atorvastatin and rapamycin activated a protein
      kinase Calpha, AMP-activated kinase, and CREB-dependent vasculoprotective
      pathway, which induced decay-accelerating factor (DAF) promoter activity via
      binding to the cAMP response element, mutation of which attenuated promoter
      activity. This response significantly increased endothelial cell surface DAF and
      enhanced protection against complement-mediated injury. Synergy with rapamycin
      was reproduced by simvastatin, whereas combining atorvastatin with cyclosporine
      or mycophenolate in place of rapamycin was ineffective. Importantly, synergy was
      reproduced in vivo, in which only atorvastatin and rapamycin therapy in
      combination was sufficient to induce DAF on murine aortic endothelium. We believe
      this pathway represents an important therapeutically inducible vasculoprotective
      mechanism for diseases mediated by pathogenic Abs and complement, including
      posttransplant vasculopathy and systemic lupus erythematosus. Although our study
      focuses on the vascular endothelium, the findings are likely to be broadly
      applicable, given the diverse cellular expression of DAF. 

PMID- 24670801
TI  - Regulatory CD4+ T cells promote B cell anergy in murine lupus.
AB  - To prevent autoimmunity, anergy of autoreactive B cells needs to be maintained,
      together with the suppression of hyperactive B cells. We previously reported that
      CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) can directly suppress
      autoantibody-producing autoreactive B cells in systemic lupus erythematosus. In
      this article, we show that Tregs can also reduce the production of autoantibodies
      in (NZB * NZW)F1 mouse lupus B cells by promoting B cell anergy, both in vitro
      and in vivo. This phenomenon associated with a reduction in Ca(2+) flux in B
      cells, and CTLA-4 blockade inhibited the effects of Tregs on anergic lupus B
      cells. These findings identify a new mechanism by which Tregs can control
      production of autoantibodies in lupus B cells and, more generally, B cell
      activity in physiopathological conditions. 

PMID- 24670800
TI  - Conservation of pathogenic TCR homology across class II restrictions in anti
      ribonucleoprotein autoimmunity: extended efficacy of T cell vaccine therapy.
AB  - T cells have been shown to mediate aspects of anti-ribonucleoprotein (RNP)
      autoimmunity, and are a potential target of therapy in lupus and related
      diseases. In this study, we assessed the relevance of a conserved class of anti
      RNP T cells to autoimmune disease expression and therapy. Our data show that anti
      RNP T cell selection induced a limited set of homologous CDR3 motifs at high
      frequency. Homologous CDR3 motifs have been reported in other autoimmune
      diseases. Vaccination with irradiated anti-RNP (but not anti-tetanus toxoid)
      CD4(+) cells induced remission of anti-RNP-associated nephritis in >= 80% of
      treated mice, even with donor/recipient MHC class II mismatch, and in both
      induced and spontaneous autoimmunity. Vaccine responder sera inhibited anti-70k T
      cell proliferation and bound hybridomas expressing the conserved CDR3 motifs. Our
      data indicate that a limited set of TCR CDR3 motifs may be important for the
      pathogenesis of anti-RNP lupus and other autoimmune diseases. The ability to
      target a consistent set of pathogenic T cells between individuals and across
      class II restrictions may allow for the more practical development of a
      standardized anti-RNP T cell vaccine preparation useful for multiple patients.

PMID- 24670802
TI  - BAFF suppresses IL-15 expression in B cells.
AB  - Clinical trials have shown that BAFF inhibitors do not reduce memory B cell
      levels but can reduce the number of mature B cells. It remains uncertain whether
      BAFF affects memory-maintaining cytokines such as IL-15. We found that BAFF
      suppressed IL-15 expression in B cells from lupus-like or experimental allergic
      encephalomyelitis mice. When BAFF was blocked with atacicept-IgG, IL-15
      expression was upregulated in lupus-like or experimental allergic
      encephalomyelitis mice. Finally, we showed that BAFF suppressed IL-15 expression
      in transitional 2 B cells by reducing Foxo1 expression and inducing Foxo1
      phosphorylation. This study suggests that BAFF suppresses IL-15 expression in
      autoimmune diseases, and this opens up the possible opportunity for the clinical
      application of BAFF- and IL-15-specific therapeutic agents. 

PMID- 24670804
TI  - beta7 Integrin controls mast cell recruitment, whereas alphaE integrin modulates
      the number and function of CD8+ T cells in immune complex-mediated tissue injury.
AB  - Immune complex (IC) deposition causes significant tissue injury associated with
      various autoimmune diseases such as vasculitis. In the cascade of inflammation,
      cell-to-cell and cell-to-matrix adhesion via adhesion molecules are essential. To
      assess the role of alphaE and beta7 integrin in IC-mediated tissue injury,
      peritoneal and cutaneous reverse-passive Arthus reaction was examined in mice
      lacking alphaE integrin (alphaE(-/-)) or beta7 integrin (beta7(-/-)). Both
      alphaE(-/-) and beta7(-/-) mice exhibited significantly attenuated neutrophil
      infiltration in the peritoneal and cutaneous Arthus reaction. beta7 integrin
      deficiency, not alphaE integrin deficiency, significantly reduced the number of
      mast cells in the peritoneal cavity, which was consistent with the result that
      mast cells expressed only alpha4beta7 integrin, not alphaEbeta7 integrin. alphaE(
      /-) mice instead revealed the reduction of CD8(+) T cells in the peritoneal
      cavity, and nearly half of them in wild-type mice expressed alphaE integrin.
      These alphaE(+)CD8(+) T cells produced more proinflammatory cytokines than
      alphaE(-)CD8(+) T cells, and adoptive transfer of alphaE(+)CD8(+) T cell into
      alphaE(-/-) recipients restored cutaneous and peritoneal Arthus reaction. These
      results suggest that in the peritoneal and cutaneous reverse-passive Arthus
      reaction, alpha4beta7 integrin is involved in the migration of mast cells for
      initial IC recognition. alphaEbeta7 integrin, in contrast, contributes by
      recruiting alphaE(+)CD8(+) T cells, which produce more proinflammatory cytokines
      than alphaE(-)CD8(+) T cells and amplify IC-mediated inflammation. 

PMID- 24670803
TI  - Engineering of a novel anti-CD40L domain antibody for treatment of autoimmune
      diseases.
AB  - CD40-CD40L interactions play a critical role in regulating immune responses.
      Blockade of CD40L by Abs, such as the anti-CD40L Ab 5c8, demonstrated positive
      clinical effects in patients with autoimmune diseases; however, incidents of
      thromboembolism (TE) precluded further development of these molecules. In this
      study, we examined the role of the Fc domain interaction with FcgammaRs in
      modulating platelet activation and potential for TE. Our results show that the
      interaction of the 5c8 wild-type IgG1 Fc domain with FcgammaRs is responsible for
      platelet activation, as measured by induction of PAC-1 and CD62P. A version of
      5c8 with a mutated IgG1 tail was identified that showed minimal FcgammaR binding
      and platelet activation while maintaining full binding to CD40L. To address
      whether Fc effector function is required for immunosuppression, a potent Ab
      fragment, termed a "domain Ab" (dAb), against murine CD40L was identified and
      fused to a murine IgG1 Fc domain containing a D265A mutation that lacks Fc
      effector function. In vitro, this dAb-Fc demonstrated comparable potency to the
      benchmark mAb MR-1 in inhibiting B cell and dendritic cell activation.
      Furthermore, the anti-CD40L dAb-Fc exhibited a notable efficacy comparable to MR
      1 in various preclinical models, such as keyhole limpet hemocyanin-induced Ab
      responses, alloantigen-induced T cell proliferation, "heart-to-ear"
      transplantation, and NZB * NZW F1 spontaneous lupus. Thus, our data show that
      immunosuppression and TE can be uncoupled and that a CD40L dAb with an inert Fc
      tail is expected to be efficacious for treating autoimmune diseases, with reduced
      risk for TE. 

PMID- 24670805
TI  - Inhibition of GTPase Rac1 in endothelium by 6-mercaptopurine results in
      immunosuppression in nonimmune cells: new target for an old drug.
AB  - Azathioprine and its metabolite 6-mercaptopurine (6-MP) are well established
      immunosuppressive drugs. Common understanding of their immunosuppressive
      properties is largely limited to immune cells. However, in this study, the
      mechanism underlying the protective role of 6-MP in endothelial cell activation
      is investigated. Because 6-MP and its derivative 6-thioguanosine-5'-triphosphate
      (6-T-GTP) were shown to block activation of GTPase Rac1 in T lymphocytes, we
      focused on Rac1-mediated processes in endothelial cells. Indeed, 6-MP and 6-T-GTP
      decreased Rac1 activation in endothelial cells. As a result, the compounds
      inhibited TNF-alpha-induced downstream signaling via JNK and reduced activation
      of transcription factors c-Jun, activating transcription factor-2 and, in
      addition, NF kappa-light-chain-enhancer of activated B cells (NF-kappaB), which
      led to decreased transcription of proinflammatory cytokines. Moreover, 6-MP and 6
      T-GTP selectively decreased TNF-alpha-induced VCAM-1 but not ICAM-1 protein
      levels. Rac1-mediated generation of cell membrane protrusions, which form docking
      structures to capture leukocytes, also was reduced by 6-MP/6-T-GTP. Consequently,
      leukocyte transmigration was inhibited after 6-MP/6-T-GTP treatment. These data
      underscore the anti-inflammatory effect of 6-MP and 6-T-GTP on endothelial cells
      by blocking Rac1 activation. Our data provide mechanistic insight that supports
      development of novel Rac1-specific therapeutic approaches against chronic
      inflammatory diseases. 

PMID- 24670806
TI  - Engagement of SLAMF2/CD48 prolongs the time frame of effective T cell activation
      by supporting mature dendritic cell survival.
AB  - Signaling lymphocyte activation molecule family (SLAMF)2/CD48 is a coactivator
      and adhesion molecule on cells with hematopoietic origin. It ligates mainly
      SLAMF4 on effector/memory CD8(+) T cells and NK cells, suggesting a potential
      role during viral infection, with SLAMF2 acting as a ligand to activate SLAMF4
      bearing cells. The ability of SLAMF2 to signal on its own after it is engaged and
      the functional consequences are largely unknown. We found that cytosolic DNA
      activated dendritic cells (DCs) upregulate the expression of SLAMF2 molecules.
      Using anti-SLAMF2 Ab and SLAMF4 recombinant protein, we found that SLAMF2
      engagement activates immature DCs and, more interestingly, prolongs the survival
      of DNA-activated DCs by inhibiting IFN-beta production and IFN-beta-induced
      apoptosis and promotes the production of the granzyme B inhibitor protease
      inhibitor-9. Thus, SLAMF2 can serve as a survival molecule for DNA-activated DCs
      during their interaction with SLAMF4-expressing cytotoxic T cells. Based on our
      results, we propose that SLAMF2 engagement regulates adaptive immune responses by
      providing longer access of putative APCs to virus-specific effector T cells by
      prolonging the time frame of effective stimulation. 

PMID- 24670807
TI  - Age-enhanced endoplasmic reticulum stress contributes to increased Atg9A
      inhibition of STING-mediated IFN-beta production during Streptococcus pneumoniae
      infection.
AB  - Pneumococcal infections remain a leading cause of death in persons >= 65 y of
      age. Recent reports have illustrated detrimental changes in the endoplasmic
      reticulum stress response or unfolded protein response in aging and age-related
      diseases; however, the relationship between aging, the unfolded protein response,
      and innate immune responses to Streptococcus pneumoniae has not been fully
      elucidated. Our results illustrate that stimulator of IFN genes-mediated
      production of IFN-beta during S. pneumoniae infection is decreased in aged hosts.
      Enhanced endoplasmic reticulum stress in response to S. pneumoniae augmented
      inositol-requiring protein 1/X-box binding protein 1-mediated production of
      autophagy-related gene 9 (Atg9a). Knockdown of Atg9a or treatment with
      gemcitabine HCl resulted in enhanced stimulator of IFN genes-mediated production
      of IFN-beta by aged macrophages. Consecutive treatments with gemcitabine during
      in vivo S. pneumoniae infection decreased morbidity and mortality in aged hosts,
      which was associated with decreased Atg9a expression, increased IFN-beta
      production, and improved bacterial clearance from lung tissue. Taken together,
      data presented in this study provide new evidence as to why older persons are
      more susceptible to S. pneumoniae, and provide a possible mechanism to enhance
      these responses, thereby decreasing morbidity and mortality in this population.

PMID- 24670808
TI  - The effect of mobility on sexual risk behaviour and HIV infection: a cross
      sectional study of men who have sex with men in southern India.
AB  - OBJECTIVES: Mobility is an important factor contributing to the spread of HIV
      among key population at risk for HIV; however, research linking this relationship
      among men who have sex men (MSM) is scarce in India. This study examines the
      association between mobility and sexual risk behaviour and HIV infection among
      MSM in southern India. METHODS: Data are drawn from a cross-sectional
      biobehavioural survey of 1608 self-identified MSM from four districts of Andhra
      Pradesh in India, recruited through a probability-based sampling in 2009-2010.
      Logistic regression models were used to estimate odds ratios and 95% CIs for
      sexual risk behaviours (unprotected sex with any male partner) and HIV infection
      based on the mobility status (travelled and had sex in the past year) after
      adjusting for sociodemographics and risk behaviours. RESULTS: Of the 1608 MSM,
      one-fourth (26%) were mobile. Of these, three-fourths had travelled across
      districts but within the state (56%), and one-fifth (20%) across states. As
      compared to non-mobile MSM, a higher proportion of MSM who were mobile across
      districts (adjusted (OR=1.42, 95% CI 1.04 to 1.95) or states (adjusted OR=3.20,
      95% CI 1.65 to 6.17) reported having unprotected sex with any male sexual
      partner. Further, mobility across districts (adjusted OR=1.43, 95% CI 1.01 to
      2.03) or states (adjusted OR=2.45, 95% CI 1.46 to 4.10) was significantly
      associated with HIV infection. CONCLUSIONS: Mobile MSM have a higher likelihood
      of contracting HIV. Interventions extending the ways to reach out to MSM with
      greater mobility may augment ongoing efforts to reduce the spread of HIV/AIDS in
      India.

PMID- 24670809
TI  - A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells
      for the lysis of CD30+ tumor cells.
AB  - To improve recruitment and activation of natural killer (NK) cells to lyse tumor
      cells, we isolated a human anti-CD16A antibody with similar affinity for the
      CD16A 158F/V allotypes, but no binding to the CD16B isoform. Using CD16A
      targeting Fv domains, we constructed a tetravalent bispecific CD30/CD16A tandem
      diabody (TandAb(r)) consisting solely of Fv domains. This TandAb has two binding
      sites for CD16A and two for CD30, the antigen identifying Hodgkin lymphoma cells.
      The binding and cytotoxicity of the TandAb were compared with antibodies with
      identical anti-CD30 domains: (1) a native IgG, (2) an IgG optimized for binding
      to Fc receptors, and (3) a bivalent bispecific CD30/CD16A diabody. Due to its
      CD16A-bivalency and reduced koff, the TandAb was retained longer on the surface
      of NK cells than the IgGs or the diabody. This contributed to the higher potency
      and efficacy of the TandAb relative to those of the other anti-CD30 antibodies.
      TandAb cytotoxicity was independent of the CD16A allotype, whereas the anti-CD30
      IgGs were substantially less cytotoxic when NK cells with low affinity CD16A
      allotype were employed. TandAb activation of NK cells was strictly dependent on
      the presence of CD30(+) target cells. Therefore, the CD30/CD16A TandAb may
      represent a promising therapeutic for the treatment of Hodgkin's lymphoma;
      further, anti-CD16A TandAbs may function as potent immunotherapeutics that
      specifically recruit NK cells to destroy cancer cells. 

PMID- 24670811
TI  - Phenotyping neuropathic pain patients: implications for individual therapy and
      clinical trials.
AB  - PURPOSE OF REVIEW: The sensory phenotype can be used as a surrogate marker of
      underlying mechanisms of pain generation and is assessed by tools like the
      Quantitative Sensory Testing, Patient Reported Outcomes or the Capsaicin Response
      Test. In order to establish an individualized, mechanism-based treatment of pain,
      it has to be demonstrated that subgroups of patients with a distinct sensory
      phenotype respond differently to a certain treatment. RECENT FINDINGS:
      Retrospective analyses of several clinical trials revealed that the presence of
      certain somatosensory abnormalities in the painful area was associated with a
      better treatment outcome. Examples will be discussed in this article, showing
      that somatosensory phenotyping of patients with neuropathic pain is a promising
      method to subgroup patients in order to predict their response to treatment.
      SUMMARY: The discussed trials show the importance of the development of an
      individualized pain therapy. Up to now, no clinical trial has prospectively used
      the sensory phenotype as an inclusion or stratification criterion. Academic
      researchers and pharmaceutical industry should be encouraged to implement this
      approach in future trial designs.

PMID- 24670810
TI  - Serotonin, 5HT1 agonists, and migraine: new data, but old questions still not
      answered.
AB  - PURPOSE OF REVIEW: The serotonergic system has long been linked to migraine but
      recent studies highlight how much is still unclear about this link. And recent
      data add to the uncertainty of where/how triptans act and why they are headache
      specific. RECENT FINDINGS: Markers of 5HT levels in the brains of migraine
      patients show no changes between attacks. Several recent meta-analyses show the
      most convincing data on genetic differences in the serotonergic system for 5HT
      transporters. Findings of additional triptan actions on peripheral
      trigeminovascular neurons and in the hypothalamus add more fuel to the debate on
      where these drugs act. A growing list of studies show efficacy of multiple
      triptans and other 5HT1b/1d agonists in preclinical models of nonheadache pain
      arguing for reevaluation of whether these drugs have efficacy in other pain
      states. Despite these issues, serotonergic drugs continue to be the gold standard
      for abortive agents with new members on the horizon (5HT1f agonists). SUMMARY:
      Given the clear efficacy of serotonergic drugs for migraine, continued study on
      the role of the endogenous 5HT system may lead to more novel therapies. And with
      the list of studies demonstrating efficacy triptans in models of nonheadache,
      clinical studies should address whether these drugs work for other types of pain.

PMID- 24670812
TI  - Metagenomic analysis of nitrate-reducing bacteria in the oral cavity:
      implications for nitric oxide homeostasis.
AB  - The microbiota of the human lower intestinal tract helps maintain healthy host
      physiology, for example through nutrient acquisition and bile acid recycling, but
      specific positive contributions of the oral microbiota to host health are not
      well established. Nitric oxide (NO) homeostasis is crucial to mammalian
      physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide
      pathway has been shown to provide bioactive NO from dietary nitrate sources.
      Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria,
      since humans lack this enzyme activity. This pathway appears to represent a newly
      recognized symbiosis between oral nitrate-reducing bacteria and their human hosts
      in which the bacteria provide nitrite and nitric oxide from nitrate reduction.
      Here we measure the nitrate-reducing capacity of tongue-scraping samples from six
      healthy human volunteers, and analyze metagenomes of the bacterial communities to
      identify bacteria contributing to nitrate reduction. We identified 14 candidate
      species, seven of which were not previously believed to contribute to nitrate
      reduction. We cultivated isolates of four candidate species in single- and mixed
      species biofilms, revealing that they have substantial nitrate- and nitrite
      reduction capabilities. Colonization by specific oral bacteria may thus
      contribute to host NO homeostasis by providing nitrite and nitric oxide.
      Conversely, the lack of specific nitrate-reducing communities may disrupt the
      nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency.
      These findings may also provide mechanistic evidence for the oral systemic link.
      Our results provide a possible new therapeutic target and paradigm for NO
      restoration in humans by specific oral bacteria. 

PMID- 24670813
TI  - Normal ranges and variability of novel urinary renal biomarkers in Sprague-Dawley
      Rats: comparison of constitutive values between males and females and across
      assay platforms.
AB  - Differences were examined between male and female Sprague-Dawley rats in basal
      levels of a wide range of urinary biomarkers, including 7 recently qualified
      biomarkers. The data were generated from urine samples collected on 3 occasions
      from untreated rats included in a study of the effect of gentamicin
      nephrotoxicity on urinary renal biomarkers, reported in a companion article in
      this journal (Gautier et al. 2014). The performance of multiple assays (9
      singleplex assays and 2 multiplex platforms from Rules Based Medicine [RBM] and
      Meso Scale Discovery [MSD]) was evaluated, and normal ranges and variability
      estimates were derived. While variability was generally greater on the RBM
      platform than other assays, the more striking difference in the results from
      different assays was in magnitude. Where differences were observed between assays
      for an individual biomarker, they were seen in both sexes and consistent across
      samples collected at different time points. Differences of up to 15-fold were
      observed for some biomarker values between assays indicating that results
      generated using different assays should not be compared. For 8 biomarkers, there
      was compelling evidence for a sex difference. Baseline values in males were
      significantly higher than in females for total protein, beta2-microglobulin,
      clusterin, cystatin-C, glutathione-S-transferase (GST-alpha), tissue inhibitor of
      metalloproteinases (TIMP-1), and vascular endothelial growth factor (VEGF);
      female values were significantly higher than that of males for albumin. The
      largest sex differences (male greater than female by 2- to 11-fold) were seen
      with beta2-microglobulin, GST-alpha, and TIMP-1. These data add substantially to
      the limited body of knowledge in this area and provide a useful framework for
      evaluation of the potential relevance of sex differences in the diagnostic
      performance of these biomarkers. 

PMID- 24670814
TI  - Quantitative evaluation of drug-induced microvascular constriction in mice kidney
      using a novel tool for 3D geometrical analysis of ex vivo organ vasculature.
AB  - The analysis of organ vasculature, and more specifically organ microvasculature,
      carries special importance for toxicological sciences, and especially for
      evaluation of drug-induced vascular toxicity. This field presents a special
      challenge in nonclinical drug safety assessments since there are currently no
      reliable microvascular toxicity biomarkers. Therefore, we aimed to systematically
      investigate the use of microvascular 3D geometrical analysis of corrosion casts
      for evaluation of drug-induced vascular toxicity, utilizing a novel image
      investigation tool that allows full 3D-quantified geometrical analysis of the
      entire vascular tree structure. Vascular casts of kidneys from control and low-
      and high-dose ephedrine/caffeine-treated mice were scanned by a micro CT, and
      images were processed and analyzed using the VasculomicsTM platform. All
      evaluations were performed on the kidney cortex. Treatment resulted in a
      significant and dose-related reduction in overall microvessel density throughout
      the kidney cortex. This effect was most pronounced for vessels with diameters
      between 25 um and 35 um, and affected mostly vessels located in the superficial
      part of the kidney cortex. The use of 3D analysis tools in drug-induced vascular
      toxicity studies allows for very high resolution and characterization of drug
      effects on the microvasculature and can be used as a valuable tool in drug safety
      assessments.

PMID- 24670815
TI  - Estrous cycle-dependent morphology in the reproductive organs of the female
      Gottingen minipig.
AB  - The present study describes the normal histology of female reproductive organs
      during the estrous cycle in the Gottingen minipig. For this purpose, sexually
      mature females were sacrificed at different phases of the cycle
      (follicular/proliferation, ovulation, and early-, mid-, and late-luteal/secretory
      phase). Ovaries, uterus, cervix, vagina, and mammary gland tissues were processed
      for microscopic evaluation. Sexual maturity was assured by selecting females in
      which at least 1 progesterone peak was measured. Stage-distinguishing features in
      ovaries were the Graafian follicles (disrupted vs. nondisrupted) and corpora
      lutea of recent and preceding cycles (size, cell morphology, and structural
      composition). In the uterus, stage-specific markers were epithelial morphology,
      secretory activity (using periodic acid-Schiff/hematoxylin staining), and
      epithelial mitosis and/or apoptosis. The other reproductive organs were not
      suitable to discriminate between the different phases of the cycle due to a high
      morphologic variability (mammary gland, and vagina) or absence of clear
      morphologic differences between the phases (cervix). The increased use of young
      minipigs (frequently immature/peripubertal) in preclinical testing requires more
      knowledge on the histologic cyclic changes. With the present morphologic
      description of the morphologic characteristics of the reproductive tract in
      recently ovulating minipigs, a guidance for staging the estrous cycle and
      determination of sexual immaturity is provided.

PMID- 24670816
TI  - The stage-specific testicular germ cell apoptotic response to low-dose radiation
      and 2,5-hexanedione combined exposure. II: qRT-PCR array analysis reveals dose
      dependent adaptive alterations in the apoptotic pathway.
AB  - Testicular effects of chemical mixtures may differ from those of the individual
      chemical constituents. This study assessed the co-exposure effects of the model
      germ cell- and Sertoli cell-specific toxicants, X-irradiation (x-ray), and 2,5
      hexanedione (HD), respectively. In high-dose studies, HD has been shown to
      attenuate x-ray-induced germ cell apoptosis. Adult rats were exposed to different
      levels of x-ray (0.5 Gy, 1 Gy, and 2 Gy) or HD (0.33%), either alone or in
      combination. To assess cell type-specific attenuation of x-ray effects with HD co
      exposure, we used laser capture microdissection (LCM) to enrich the targeted cell
      population and examine a panel of apoptosis-related transcripts using PCR arrays.
      The apoptosis PCR arrays identified significant dose-dependent treatment effects
      on several genes, with downregulation of death receptor 5 (DR5), Naip2, Sphk2,
      Casp7, Aven, Birc3, and upregulation of Fas. The greatest difference in
      transcript response to exposure was seen with 0.5 Gy x-ray exposure, and the
      attenuation effect seen with the combined high-dose x-ray and HD did not persist
      into the low-dose range. Examination of protein levels in staged tubules revealed
      a significant upregulation in DR5, following high-dose co-exposure. These results
      provide insight into the testis cell-specific apoptotic response to low-dose co
      exposures of model testicular toxicants.

PMID- 24670817
TI  - Comparative uterotrophic effects of endoxifen and tamoxifen in ovariectomized
      Sprague-Dawley rats.
AB  - Endoxifen (4-hydroxy-N-desmethyl-tamoxifen), one of the major active metabolites
      of tamoxifen, has substantially greater estrogen antagonist properties and
      antiproliferative effects in breast tumor cells than tamoxifen, a mixed estrogen
      agonist/antagonist. An associated risk of endometrial cancer and hyperplasia has
      been linked to the estrogen agonist properties of tamoxifen. We evaluated
      endoxifen using a classic uterotrophic effects method. Rats were given endoxifen
      or tamoxifen orally for 3 days. Estradiol was the positive control. Endoxifen and
      tamoxifen plasma levels exceeded those previously observed clinically. Uterine
      weight was 3-fold higher in the estradiol group than in the tamoxifen or
      endoxifen groups, which did not differ from vehicle controls. Tamoxifen and
      endoxifen caused a greater increase in luminal epithelial cell height than
      estradiol. Both tamoxifen and endoxifen produced an increase in the stromal BrdU
      labeling index (LI) that was <= estradiol and inversely related to dose, but did
      not affect luminal epithelial cell BrdU LI. As expected, estradiol increased
      luminal epithelial cell proliferation. These results indicate that endoxifen
      induces uterotrophic effects, but is less potent than estradiol in eliciting
      these effects. Given prior preclinical observations that endoxifen has superior
      antitumor activity than tamoxifen, the observations of similar uterine effects
      suggest that the endoxifen risk/benefit ratio may be superior to tamoxifen.

PMID- 24670818
TI  - Hemodynamic correlates of drug-induced vascular injury in the rat using high
      frequency ultrasound imaging.
AB  - Several classes of drugs have been shown to cause drug-induced vascular injury
      (DIVI) in preclinical toxicity studies. Measurement of blood flow and vessel
      diameter in numerous vessels and across various tissues by ultrasound imaging has
      the potential to be a noninvasive translatable biomarker of DIVI. Our objective
      was to demonstrate the utility of high-frequency ultrasound imaging for measuring
      changes in vascular function by evaluating blood flow and vessel diameter in the
      superior mesenteric arteries (SMA) of rats treated with compounds that are known
      to cause DIVI and are known vasodilators in rat: fenoldopam, CI-1044, and SK&F
      95654. Blood flow, vessel diameter, and other parameters were measured in the SMA
      at 4, 8, and 24 hr after dosing. Mild to moderate perivascular accumulations of
      mononuclear cells, neutrophils in tunica adventitia, and superficial tunica media
      as well as multifocal hemorrhage and necrosis in the tunica media were found in
      animals 24 hr after treatment with fenoldopam and SK&F 95654. Each compound
      caused marked increases in blood flow and shear stress as early as 4 hr after
      dosing. These results suggest that ultrasound imaging may constitute a functional
      correlate for the microscopic finding of DIVI in the rat. 

PMID- 24670819
TI  - Cancer cell dormancy in novel mouse models for reversible pancreatic cancer: a
      lingering challenge in the development of targeted therapies.
AB  - Significant advances have been made in the identification of key molecular
      pathways that play pivotal roles in the initiation and progression of pancreatic
      ductal adenocarcinoma (PDAC). Among the common genetic and epigenetic changes,
      oncogenic mutations in Kras and upregulation of the c-Myc oncogene are frequent
      events in PDAC. Using genetically defined in vivo models, several studies have
      recently demonstrated that expression of mutant Kras and c-Myc is equally
      important for the initiation and maintenance of pancreatic cancer. The targeted
      downregulation of a single oncogene resulted in cancer cell death at primary and
      metastatic sites. These findings are very encouraging and provide a strong
      rationale for the development of targeted therapies against these oncogenic
      drivers. Despite what seemed to be a complete response to the ablation of the
      oncogene, a few dormant cancer cells remained present, and it was demonstrated
      that they are a cellular reservoir for a swift relapse of pancreatic cancer
      following oncogene reactivation. This review summarizes the basic principles of
      cancer dormancy and the applicability of the novel genetic models for reversible
      metastatic PDAC to elucidate the role of cancer stem cells as well as biologic
      and molecular mechanisms that mediate the survival of dormant tumor cells.

PMID- 24670821
TI  - The management of ruptured abdominal aortic aneurysms.

PMID- 24670820
TI  - Modelling mutational landscapes of human cancers in vitro.
AB  - Experimental models that recapitulate mutational landscapes of human cancers are
      needed to decipher the rapidly expanding data on human somatic mutations. We
      demonstrate that mutation patterns in immortalised cell lines derived from
      primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens
      recapitulate key features of mutational signatures observed in human cancers. In
      experiments with several cancer-causing agents we obtained high genome-wide
      concordance between human tumour mutation data and in vitro data with respect to
      predominant substitution types, strand bias and sequence context. Moreover, we
      found signature mutations in well-studied human cancer driver genes. To explore
      endogenous mutagenesis, we used MEFs ectopically expressing activation-induced
      cytidine deaminase (AID) and observed an excess of AID signature mutations in
      immortalised cell lines compared to their non-transgenic counterparts. MEF
      immortalisation is thus a simple and powerful strategy for modelling cancer
      mutation landscapes that facilitates the interpretation of human tumour genome
      wide sequencing data. 

PMID- 24670822
TI  - Ruptured abdominal aortic aneurysms: is open surgery an outdated operation?
AB  - The advent of endovascular aneurysm repair (EVAR) has revolutionized the
      treatment of abdominal aortic aneurysms. EVAR has evolved into the preferred
      treatment for abdominal aortic aneurysms with suitable anatomy. Several
      randomized clinical trials have confirmed that EVAR reduces short-term morbidity
      and mortality. Despite vast improvements in diagnostic imaging, open surgical
      repair techniques and the care of critically ill patients over the past two
      decades rupture of abdominal aortic aneurysms still carries an extremely high
      morbidity and mortality. To improve outcomes in treatment of rAAA a movement has
      occurred away from open repair and toward EVAR as a paradigm shift that may help
      to improve otherwise dismal results. In the past 10 years, numerous studies
      including meta-analyses, administrative databases and randomized control trials
      have investigated the presumed advantages of EVAR over open repair. This review
      summarizes the world wide experience for ruptured AAA repair and addresses the
      role for standardization of care with the use of aortic aneurysm protocols. 

PMID- 24670823
TI  - The role of permissive hypotension in the management of ruptured abdominal aortic
      aneurysms.
AB  - The aim of this review was to explore current literature pertaining to the use of
      permissive hypotension in the treatment of abdominal aortic aneurysms. A
      literature search using Metalib, a database search engine, provided at the Royal
      Free and University College of London (UCL) yielded articles using the keywords
      "permissive hypotension" and "hypotensive resuscitation" when linked to
      "abdominal aortic aneurysm" and "rupture". The articles studying permissive
      hypotension in animals and humans in trauma, and in patients with abdominal
      aortic aneurysm were reviewed. The result of this search was a large volume of
      experimental studies of trauma in animals giving satisfactory evidence of the
      physiological benefit of this concept of resuscitation in trauma. There were some
      randomized trials in humans in trauma suggesting benefit. The safety of
      permissive hypotension in patients with ruptured aortic aneurysms was documented
      and found to be widespread, but there were no randomized trials directly
      comparing this practice. Evidence from a prospective randomized study on the
      modality of treatment of ruptured aortic aneurysms suggest that the level of
      blood pressure is associated with the mortality and a prospective cohort study
      suggests that, using the complementary concept of "delayed volume resuscitation",
      the total volume of preoperative fluid resuscitation independent of the blood
      pressure is predictive of the risk of perioperative death in ruptured aortic
      aneurysms. To this end, recent clinical publications are now supportive of
      control of both the volume of preoperative fluid given and blood pressure in this
      group of patients but clinical studies are few. 

PMID- 24670824
TI  - Balloon control for ruptured AAAs: when and when not to use?
AB  - Emergency endovascular aneurysm repair (eEVAR) for ruptured abdominal aortic
      aneurysm (rAAA) must be carried out instantly. This requires firm logistics that
      include the ability to cross-clamp the aorta without delay. The present article
      focuses on the technique of balloon control of the aorta in eEVAR with aspects on
      indications as well as the organization of this type of vascular service.
      Transfemoral insertion of the occlusion balloon under local anesthesia is
      advocated and described. The use of dual balloons shortens the time of visceral
      ischemia without necessitating repeat declamping until the aneurysm has been
      completely excluded. Staged declamping upon completion is necessary just as in
      open repair. A "balloon test" is suggested to better identify those high risk
      patients with a rAAA who may benefit from endovascular rAAA repair. 

PMID- 24670825
TI  - One hundred percent of ruptured aortic abdominal aneurysms can be treated
      endovascularly if adjunct techniques are used such as chimneys, periscopes and
      embolization.
AB  - Observational studies comparing endovascular aneurysm repair (EVAR) with open
      repair (OR) in ruptured abdominal aortic aneurysms (AAA) have suggested a benefit
      for EVAR but have been questioned recently by randomized controlled trials (RCT).
      A low eligibility for endovascular repair is a main limitation of these RCTs. In
      contrast, data from 473 patients from 1998 to 2011 in the Orebro/Zurich series
      show that nearly all AAA patients presenting with rupture can in fact be treated
      with EVAR with a low 30-day mortality rate (24%) and a minimal exclusion rate
      (4%). By using different adjunct techniques, such as chimneys and periscopes,
      also juxtarenal aneurysms can be treated even if simultaneous aortic balloon
      occlusion is necessary. OnyxTM embolization of the internal iliac artery in
      patients with aortoiliac aneurysms prevents back flow, thus avoiding an endoleak
      type. From May 2009 until December 2013, 70 patients arrived at Orebro University
      Hospital with a ruptured AAA diagnose. Nine percent were considered unfit for any
      intervention (including OR) and were treated medically. All of the 64 patients
      that underwent surgery were treated with EVAR and 30-day mortality in this group
      was 17 of 64 patients (27%). The mortality for patients treated with adjunct
      techniques was not significantly increased compared with patients treated with
      standard EVAR. In conclusion, our data support that open repair of ruptured AAA
      can be replaced by EVAR with appropriate management of existing adjunct
      techniques. 

PMID- 24670826
TI  - How to diagnose and treat abdominal compartment syndrome after endovascular and
      open repair of ruptured abdominal aortic aneurysms.
AB  - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are
      frequently encountered in patients treated for ruptured abdominal aortic
      aneurysms (rAAA) and carry a high morbidity and mortality risk. Despite these
      facts, IAH/ACS are still overlooked by many physicians, timely diagnosis is
      missed and treatment often inadequate. All staff involved in the treatment of
      rAAA should be aware of the risk factors predicting IAH/ACS, the profound
      implications and derangements on all organ systems, the clinical presentation,
      the appropriate measurement of intra-abdominal pressure to detect IAH/ACS and the
      current treatment options for these detrimental syndromes. This comprehensive
      review provides contemporary knowledge that should help to improve patient
      survival and long-term outcome. 

PMID- 24670827
TI  - Team training in ruptured EVAR.
AB  - Ruptured abdominal aortic aneurysms are almost always a fatal condition. The
      incidence of ruptured aortic aneurysms (rAAA) is declining, the number of teams
      is increasing and there is an increased focus on patient safety resulting in
      limited real life training opportunities to maintain or improve the technical and
      human factor skills required to manage this acute aortic pathology. The
      availability and experience of the multidisciplinary team together with
      accessibility of appropriate resuscitation and efficient logistics all influence
      the modality of rAAA repair. A standardised patient's pathway for rAAA management
      and reliable multidisciplinary team are the keys to improve patient outcomes.
      Whole rEVAR team training using high fidelity simulation may be the one answer to
      allow clinicians to learn, practice, rehearse, improve and maintain team-based
      knowledge, technical and human factor skills and team attitudes to manage this
      challenging pathology. 

PMID- 24670828
TI  - The "DEBELLUM"--lower limb multilevel treatment with drug eluting balloon-
      randomized trial: 1-year results.
AB  - AIM: The aim of the present paper was to make a report of the 12-month clinical
      outcomes of the DEBELLUM (Drug-Eluting-Balloon-Evaluation-for-Lower-Limb-
      mUltilevel-treatMent) randomized trial. METHODS: From September 2010 to March
      2011, 50 patients were randomized between drug eluting balloon (DEB, N.=25) and
      conventional angioplasty balloon (PTA, N.=25). Patients were symptomatic for
      claudication and critical limb ischemia, with de novo stenosis or occlusion in
      the femoropopliteal (SFA) and infrapopliteal (BTK) region. Only in the SFA
      primary stenting was allowed and postdilatation performed with DEB or PTA
      depending on the assigned group. RESULTS: One hundred and twenty-two lesions were
      treated: 92 (75.4%) SFA, 30 (24.6%) BTK. Twenty (40%) patients presented
      multilevel concomitant femoropopliteal and infra-popliteal lesions. Late lumen
      loss (LLL) was 0.64+/-0.9 mm in DEB group vs. 1.81+/-0.1 mm in the control group
      (P=0.01). In non-stented segment LLL was 0.63+/-0.9 mm (DEB) vs. 1.70+/-0.6 mm
      (PTA), P<0.01. In the stent subgroup was LLL 0.65+/-0.2 mm (DEB) vs. 1.91+/-0.3
      mm (PTA), P<0.01. In the femoropopliteal region the overall LLL was 0.61+/-0.8 mm
      for DEB vs. 1.84+/-0.3 mm for PTA (P=0.02). BTK the overall LLL was 0.66+/-0.9 mm
      (DEB) vs. 1.69+/-0.5 mm (PTA) (P=0.03). The overall TLR was 12.2% for DEB and
      35.3% for PTA (P<0.05). Amputation rate was 4% (DEB) vs. 12% (PTA), P=0.36.
      Thrombosis was 4% (DEB) vs. 8% (PTA), P>=0.05. Major adverse events 24% (DEB) vs.
      60% (PTA), P<0.05. ABI improved more in the DEB group: 0.81+/-0.3 vs. 0.68+/-0.13
      (P=0.02). Fontaine stage increased (from II b to I) 80% DEB vs. 56% PTA (P<0.05).
      CONCLUSION: Results confirm and reinforce initial 6-month outcomes. In.Pact DEB
      balloons can be considered efficient to reduce restenosis rate.

PMID- 24670829
TI  - Paclitaxel-coated balloons for failing peripheral bypass grafts: the BYPACS
      study.
AB  - AIM: Aim of the present study was to report the imaging and clinical outcomes of
      a prospective single-center study investigating paclitaxel-coated balloons (PCB)
      for the treatment of failing peripheral bypass grafts (BYPACS study). METHODS: In
      total, 32 patients had their failing peripheral native or synthetic bypass graft
      treated with PCB angioplasty (Group PCB). Basic inclusion criteria were any
      significant proximal or distal anastomotic stenosis confirmed by Duplex
      ultrasound (DUS; PSVR>2.5) associated with significantly reduced in-graft
      velocities (<45 cm/s) putting the graft at risk of thrombosis. Results were
      compared with a similar historical control group of 24 patients who had their
      failing peripheral bypass treated with plain uncoated balloon angioplasty (Group
      PTA). Primary endpoint was binary lesion restenosis defined as >50% stenosis of
      the treated lesion on DUS. Secondary endpoints included freedom from target
      lesion revascularization (TLR) defined as a patent peripheral bypass graft
      regardless of restenosis but without any repeat intervention (driven by reduced
      in-graft velocities <45 cm/s), major amputations and graft thrombosis.
      Multivariable Cox proportional hazards regression analysis was applied to adjust
      for confounding factors of heterogeneity. Results are reported as Cox-adjusted
      hazard ratios (HR and 95% CI). RESULTS: Baseline variables were equally
      distributed between the two groups. Median follow-up was 7 months in group PCB
      and 8 months in group PTA. Rates of binary restenosis were similar between the 2
      groups (HR=1.08, 95% CI=0.49-2.40; P=0.84). Freedom from TLR was also similar
      (HR=0.97, 95% CI=0.36-2.66; P=0.88). One amputation occurred in the PCB group and
      2 in the PTA (P=0.58). Four events of bypass thrombosis occurred in each group
      (P=0.71). CONCLUSION: PCB does not significantly inhibit restenosis or improve
      freedom from repeat angioplasty after treatment of failing peripheral arterial
      vein or synthetic bypass grafts.

PMID- 24670830
TI  - Pedal access in critical limb ischemia.
AB  - Critical limb ischemia (CLI) commonly involves popliteal and infrapopliteal
      arterial occlusions. Surgical revascularization may be limited by poor distal
      targets, lack of autologous vein, and co morbid conditions. Endovascular therapy
      may be an option even in this group of patients with no surgical options, but is
      limited by the need to first cross these chronic total occlusions. Lesions that
      are uncrossable in antegrade fashion are often easily crossed via retrograde
      approach. The pedal approach (via anterior tibial, posterior tibial, or peroneal
      arteries) is a viable approach in limb salvage interventions where occlusions
      cannot be crossed with antegrade approach. A 13-step technique utilizing
      transpedal approach in my first 228 patients treated by this approach who had
      presented with CLI and had failed attempts at antegrade crossing of the
      occlusions is described. In this group of patients, transpedal approach was only
      utilized in patients with CLI. No claudicants were included. The pedal arteries
      were accessed successfully in 217/228 (95%) patients. Once pedal access was
      achieved successful intervention was accomplished in 199/217 (93%). There were no
      bleeding complications and only one pedal occlusion. 

PMID- 24670831
TI  - Effectiveness of Zilver PTX eluting stent in TASC C/D lesions and restenosis.
AB  - AIM: The indication for use of drug-eluting stents (DES) in lower limb arteries
      is still undefined. We report our series of patients treated with Zilver PTS DES,
      in treating in-stent restenosis (ISR) and Trans-Atlantic Inter-Society Consensus
      Document on Management of Peripheral Arterial Disease (TASC) C/D femoropopliteal
      lesions. METHODS: The Zilver PTX DES is a self-expanding nitinol stent with a
      polymer-free Paclitaxel coating. Patients with symptomatic de novo TASC C/D
      lesions or IRS lesions of femoropopliteal segment were eligible for enrollment.
      We evaluated patients at one month, six months and one year after treatment. We
      used clinical evaluation criteria and US Doppler for primary and secondary
      patency-free rates. RESULTS: From November 2010 to November 2012, we treated 69
      patients with DES Zilver PTX. Indication to treat was given in 36 lesions (52%)
      by an ISR and in 33 cases (48%) by a TASC C/D lesion. Lesions were staged in the
      superficial femoral artery (SFA) level in 59 patients (85.6%), in the popliteal
      artery in 6 patients (8.7%), in a femoropopliteal bypass in 4 patients (5.7%).
      The mean follow-up was 5.3 months (range 1-24). At 12 months the overall primary
      patency was 85.5%, secondary patency 89.8% and limb salvage 100%. CONCLUSION:
      Zilver PTX DES seems to be effective in treating TASC C/D lesions and ISR in
      femoropopliteal lesions at short term. Therefore DES should be recommended when
      treating those complex lesions.

PMID- 24670832
TI  - Early and long-term outcomes after open or endovascular repair for abdominal
      aortic aneurysms in high-risk patients.
AB  - AIM: The aim of our study was to evaluate the earlier and long term survival as
      well the postoperative complications in high-risk patients who received
      endovascular aortic repair (EVAR) as first choice, or open repair when anatomical
      requirements for EVAR were not met. METHODS: Between January 2005 and January
      2010, 593 patients underwent procedures for elective abdominal aortic aneurysm
      (AAA) repair; 172 of these were considered at high risk according to the American
      Society of Anesthesiology (ASA) score (ASA III and IV): 150 high-risk patients
      were males (mean age 72.7, range 53-93 years) and 22 females (mean age 72.9
      years, range 60-90 years). The median AAA diameter was 64 (53-75) mm in the open
      repair group and 62 (55-70) mm in the EVAR group. 121 patients underwent open
      repair and 51 EVAR, respectively. RESULTS: The 30-day mortality rate was 0% in
      the EVAR group and 2.4% (3/121) in the open repair group (P=0.26). Long-term
      results showed: no EVAR-related mortality, no late conversion to open repair in
      the EVAR group was required during follow-up. No aneurysmal expansion was
      observed. In the open repair group, no graft-related events were observed during
      follow-up. The mean follow-up for survival analysis was 1542 days. Overall 5-year
      survival was 71.7% (SE=4.2%). Survival during follow-up was 92.2%, 86.1%, 76.2%,
      65.9% and 61.8% at 12, 24,36,48,60 months respectively in EVAR Group. Open Group
      present long term survival of 95%, 88.9%, 83.9%, 79.7%, 76% at 12, 24, 36, 48, 60
      months respectively. CONCLUSION: Our results in open repair surgery show a
      perioperative low mortality rate with high survival rate in long term. This
      result could be successfully achieved even in high-risk patients unsuitable for
      EVAR.

PMID- 24670833
TI  - Endovascular treatment of extracranial vertebral artery aneurysm and aberrant
      right subclavian artery aneurysm.
AB  - We report an endovascular approach that used to treat a symptomatic extracranial
      vertebral artery aneurysm associated to an asymptomatic aberrant right subclavian
      artery aneurysm. A 54-year-old man presented with neck pain, vertigo and loss of
      balance. The computed tomography (CT) scan demonstrated a left extracranial
      vertebral artery aneurysm that compressed and eroded the C5 vertebra associated
      to an aberrant right subclavian artery aneurysm. Endovascular exclusion of the
      vertebral aneurysm using a covered stent and a hybrid treatment of the aberrant
      subclavian artery aneurysm were performed. The 13th month follow-up CT scan
      confirmed the stent-grafts and supra-aortic vessels patency. The endovascular
      treatment represents a good option for these complex pathologies with excellent
      immediate results, reduces the complication rate and the hospital stay if
      compared to open repair. Long-term follow-up is necessary. To our knowledge this
      is a unique case in the literature. 

PMID- 24670834
TI  - Efficacy of TachoSil(r) as a sutureless hemostatic patch to repair a perforation
      of the interventricular groove during endocardial radiofrequency ablation.
AB  - Catheter ablation is a well-established therapeutic option for management of
      recurrent ventricular tachycardia in patients with ischemic/non-ischemic heart
      disease and procedural complications include a mortality rate of up to 3% and a
      risk of major complications up to 10%. Cardiac perforation following a catheter
      ablation is rare but serious complication and occurs in 1% of ventricular
      ablation procedures. The appropriate surgical repair may be challenging and need
      cardiopulmonary bypass support according to the location of the lesion and the
      hemodynamic status of the patient. We report the case of a free wall right
      ventricular perforation of the interventricular groove with cardiac tamponade
      following catheter ablation for recurrent ventricular tachycardia. Due to the
      proximity of the left anterior descending artery and the extreme fragility of
      tissues, the patient was treated successfully by a sutureless patch technique
      using a fibrin tissue-adhesive collagen fleece (TachoSil(r)). This technique is a
      safe and effective surgical option to repair a ventricular perforation especially
      when the ventricular tissues are fragile. It is simple and enable to realize
      surgical repair also if the localization of tear is difficult to access and
      without the need for cardiopulmonary bypass support if hemodynamic conditions are
      stable. 

PMID- 24670835
TI  - Efficacy and safety of tolvaptan in heart failure patients with volume overload.
AB  - BACKGROUND:  Loop diuretics are commonly used in heart failure (HF) patients, but
      they are sometimes associated with insufficient response as well as adverse
      events. In such diuretics-resistant cases, tolvaptan, a vasopressin type 2
      receptor antagonist, shows the improvement of volume overload without electrolyte
      imbalance. Tolvaptan was launched in Japan in 2010, and a post-marketing
      surveillance has been performed to evaluate the safety and efficacy of tolvaptan
      in real-world clinical settings. METHODS AND RESULTS:  HF patients with
      insufficient response to loop diuretics were enrolled: 1,053 to evaluate for
      efficacy and 1,057 patients for the safety assessment. Decreases in body weight
      from baseline were 1.0+/-1.6kg at day 2 and increases in urine volume were 631+/
      1,179ml at day 1 (both P<0.0001 vs. baseline). Congestive symptoms were
      significantly improved within 14 days. Adverse drug reactions (ADR) were observed
      in 18.7%, with thirst being the most frequent ADR (10%). Hypernatremia was a
      complication in 40 patients (3.8%). Predictive factors for the occurrence of
      hypernatremia were the starting dosage of tolvaptan (15mg/day), baseline serum
      sodium level (>=142mEq/L) and serum potassium level (<3.8mEq/L) at baseline.
      CONCLUSIONS:  In the real-world clinical setting, tolvaptan demonstrated
      aquaretic efficacy in HF patients with diuretic-resistant volume overload. We
      recommend a lower dose of tolvaptan in Japanese patients with normonatremia and
      hypokalemia to prevent hypernatremia. 

PMID- 24670839
TI  - A rich bonus OVS issue addresses "discovery and clinical care".

PMID- 24670841
TI  - Radio-frequency-assisted Liver Partition with Portal vein ligation (RALPP) for
      liver regeneration.

PMID- 24670840
TI  - Pro-inflammatory, Th1, Th2, Th17 cytokines and dendritic cells: a cross-sectional
      study in chronic periodontitis.
AB  - There are a limited number of studies correlating the different stages of
      dendritic cells (DC) maturation with cytokines in individuals presented chronic
      periodontitis (CP). The aim of the study was to evaluate the correlation among
      the expression of IL-2, IL-10, IL-4, IL-6, IFN-gamma, TNF-alpha, and IL-17A with
      the presence of DC and mild-moderate or advanced CP. Gingival samples were
      obtained from 24 individuals with CP and six samples of normal mucosa (NM)
      overlapping third molar for controls of the levels of cytokines. Periodontal
      examination was performed. Immunohistochemical staining was carried out,
      revealing CD1a+ immature, Fator XIIIa+ immature, and CD83+ mature DCs. The
      inflammatory infiltrate was counted, and the cytokines were measured by flow
      cytometry. Densities of DCs and inflammatory infiltrate, cytokines, subtypes of
      CP, and clinical periodontal parameters were correlated and compared. IL-6
      expression was correlated positively with the increased numbers of CD1a+ immature
      DCs. Levels of IL-2, TNF-alpha, IFN-gamma, IL-10, and IL-17A were increased when
      compared with NM. The percentage of sites with clinical attachment level (CAL)>3
      were positively correlated with densities of inflammatory infiltrate and
      negatively correlated with densities of immature DCs. IL-6 can contribute to the
      increase of the immature DCs in the CP. Higher levels of IL-2, TNF-alpha, IFN
      gamma, IL-10, and IL-17A cytokines were observed in CP. Higher densities of
      inflammatory infiltrate as well as lower densities of immature DCs can result in
      a more severe degree of human CP.

PMID- 24670842
TI  - Reply to Letter: "Is There No Significant Difference in the Incidence of
      Anastomotic Leakage Between the Hand-sewn and Mechanical Esophagogastric
      Anastomosis?".

PMID- 24670843
TI  - Mechanical strength and rheological properties of tissue adhesives with regard to
      colorectal anastomosis: an ex vivo study.
AB  - OBJECTIVE: To compare mechanical strength and rheology of existing tissue
      adhesives in a clinically relevant test setup with regard to colorectal
      anastomosis. BACKGROUND: Little is known on the mechanical strength of tissue
      adhesives directly after application. Furthermore, rheological profiling may be
      important in understanding mechanical performance and explaining differences
      between adhesives. This study provides new data on the mechanical strength and
      rheology of a comprehensive list of tissue adhesives with regard to colorectal
      adhesiveness. METHODS: Twelve surgical tissue adhesives were included: 4
      cyanoacrylate adhesives (CA), 2 fibrin glues (FG), 3 polyethylene glycol (PEG)
      adhesives, and 3 albumin-based (AB) adhesives. Tubular rat colonic segments were
      glued together. Tensile (T), shear (S), and peel (P) strength were measured.
      Shear storage (G') and shear loss (G") moduli were also evaluated. RESULTS: CA
      adhesives were stronger than AB (T: P = 0.017; S: P = 0.064; P: P < 0.001),
      which, in turn, were stronger than PEG (T: P < 0.001; S: P < 0.001; P: P =
      0.018). PEG were stronger than FG for shear (P = 0.013) and comparable for
      tensile and peel strength (P > 0.05). Within-group variation was smallest for CA.
      Mechanical strength correlated strongly between performed tests. Rheological
      properties (G' and G") correlated strongly with mechanical strength for all
      adhesives combined. CONCLUSIONS: CA adhesives are the strongest and most
      homogenous group in terms of mechanical strength. Hydrogels (FG, AB) are
      heterogeneous, with lower mechanical strength than CA. FG are mechanically the
      weakest adhesives. Rheological profiles correlate to mechanical strength and may
      be useful for predicting mechanical performance.

PMID- 24670844
TI  - Comparative effectiveness of sphincter-sparing surgery versus abdominoperineal
      resection in rectal cancer: patient-reported outcomes in National Surgical
      Adjuvant Breast and Bowel Project randomized trial R-04.
AB  - OBJECTIVE: National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a
      randomized controlled trial of neoadjuvant chemoradiotherapy in patients with
      resectable stage II-III rectal cancer. We hypothesized that patients who
      underwent abdominoperineal resection (APR) would have a poorer quality of life
      than those who underwent sphincter-sparing surgery (SSS). METHODS: To obtain
      patient-reported outcomes (PROs) we administered two symptom scales at baseline
      and 1 year postoperatively: the Functional Assessment of Cancer Therapy
      Colorectal (FACT-C) and the European Organization for the Research and Treatment
      of Cancer module for patients with Colorectal Cancer Quality of Life
      Questionnaire (EORTC QLQ-CR38). Scoring was stratified by nonrandomly assigned
      definitive surgery (APR vs SSS). Analyses controlled for baseline scores and
      stratification factors: age, sex, stage, intended surgery, and randomly assigned
      chemoradiotherapy. RESULTS: Of 1,608 randomly assigned patients, 987 had data for
      planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale
      scores were not statistically different by surgery at 1 year. For the EORTC QLQ
      CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P =
      0.0005) at 1 year than did SSS patients. Males undergoing APR reported worse
      sexual enjoyment (43.7 vs 54.7, P = 0.02) at 1 year than did those undergoing
      SSS. For the EORTC QLQ-CR38 symptom scale scores, APR patients reported worse
      micturition symptoms than the SSS group at 1 year (26.9 vs 21.5, P = 0.03). SSS
      patients reported worse gastrointestinal tract symptoms than did the APR patients
      (18.9 vs 15.2, P < 0.0001), as well as weight loss (10.1 vs 6.0, P = 0.002).
      CONCLUSIONS: Symptoms and functional problems were detected at 1 year by EORTC
      QLQ-CR38, reflecting different symptom profiles in patients who underwent APR
      than those who underwent SSS. Information from these PROs may be useful in
      counseling patients anticipating surgery for rectal cancer.

PMID- 24670845
TI  - Protein concentration and mitochondrial content in the gastrocnemius predicts
      mortality rates in patients with peripheral arterial disease.
AB  - OBJECTIVE: This study evaluated the hypothesis that protein concentration and
      mitochondrial content in gastrocnemius biopsies from patients with peripheral
      arterial disease (PAD) predict mortality rates. BACKGROUND: PAD patients
      experience advancing myopathy characterized by mitochondrial dysfunction,
      myofiber degradation, and fibrosis in their ischemic legs, along with increased
      mortality rates. METHODS: Samples from the gastrocnemius of PAD patients were
      used for all analyses. Protein concentration was normalized to muscle wet weight,
      and citrate synthase activity (standard measure of mitochondrial content in
      cells) was normalized to muscle wet weight and protein concentration. Protein and
      citrate synthase data were grouped into tertiles and 5-year, all-cause mortality
      for each tertile was determined with Kaplan-Meier curves and compared by the
      modified Peto-Peto test. A Cox-regression model for each variable controlled for
      the effects of clinical characteristics. RESULTS: Of the 187 study participants,
      46 died during a mean follow-up of 23.0 months. Five-year mortality rate was
      highest for patients in the lowest tertile of protein concentration. Mortality
      was lowest for patients in the middle tertile of citrate synthase activity when
      normalized to either muscle wet weight or protein concentration. The mortality
      hazard ratios (HRs) from the Cox analysis were statistically significant for
      protein concentration normalized to muscle wet weight (lowest vs middle tertile;
      HR = 2.93; P = 0.008) and citrate synthase normalized to protein concentration
      (lowest vs middle tertile; HR = 4.68; P = 0.003; and lowest vs highest tertile;
      HR = 2.36; P = 0.027). CONCLUSIONS: Survival analysis of a contemporaneous
      population of PAD patients identifies protein and mitochondrial content of their
      gastrocnemius as predictors of mortality rate.

PMID- 24670846
TI  - Triage patterns for medicare patients presenting to nontrauma hospitals with
      moderate or severe injuries.
AB  - OBJECTIVE: To understand hospital-level variation in triage practices for
      patients with moderate-to-severe injuries presenting initially to nontrauma
      centers. BACKGROUND: Many patients with moderate-to-severe traumatic injuries
      receive care at nontrauma hospitals, despite evidence of a survival benefit from
      treatment at trauma centers. METHODS: We used claims from the Centers for
      Medicare and Medicaid Services to identify patients with moderate-to-severe
      injuries who presented initially to nontrauma centers. We determined whether or
      not they were transferred to a level I or II trauma center within 24 hours of
      presentation, and used multivariate regression to assess the influence of
      hospital-level factors on triage practices, after adjusting for differences in
      case mix. RESULTS: Transfer of patients with moderate-to-severe injuries to
      trauma centers occurred infrequently, with significant variation among hospitals
      (median 2%; interquartile range 1%-6%). Greater resource availability at
      nontrauma centers was associated with lower rates of successful triage, including
      the presence of neurosurgeons (relative reduction in transfer rate: 76%, P <
      0.01), more than 20 intensive care unit beds (relative reduction 30%, P < 0.01)
      and a high resident-to-bed ratio (relative reduction 23%, P < 0.01). However,
      patients were more likely to survive if they presented to hospitals with higher
      triage rates (odds of death for patients cared for at hospitals with the highest
      tercile of triage rates, compared with lowest tercile: 0.92; 95% confidence
      interval: 0.85-0.99, P = 0.02). CONCLUSIONS: Injured Medicare beneficiaries
      presenting to nontrauma centers experience high rates of undertriage, determined
      in part by increasing availability of resources. Care at hospitals with low rates
      of successful triage is associated with worse outcomes.

PMID- 24670847
TI  - Reply to Letter: "Timing of Cholecystectomy in Acute Cholecystitis".

PMID- 24670848
TI  - Association between gene expression biomarkers of immunosuppression and blood
      transfusion in severely injured polytrauma patients.
AB  - OBJECTIVE: To explore the hypothesis that blood transfusion contributes to an
      immunosuppressed phenotype in severely injured patients. BACKGROUND: Despite
      trauma patients using disproportionately large quantities of blood and blood
      products, the immunomodulatory effects of blood transfusion in this group are
      inadequately described. METHODS: A total of 112 ventilated polytrauma patients
      were recruited. Messenger RNA (mRNA) was extracted from PAXGene tubes collected
      within 2 hours of the trauma, at 24 hours, and at 72 hours. T-helper cell subtype
      specific cytokines and transcription factors were quantified using real-time
      polymerase chain reaction. RESULTS: Median injury severity score was 29. Blood
      transfusion was administered to 27 (24%) patients before the 2-hour sampling
      point. Transfusion was associated with a greater immediate rise in IL-10 (P =
      0.003) and IL-27 (P = 0.04) mRNA levels. Blood products were transfused in 72
      (64%) patients within the first 24 hours. There was an association between
      transfusion at 24 hours and higher IL-10 (P < 0.0001), lower Foxp3 (P = 0.01),
      GATA3 (P = 0.006), and RORgammat (P = 0.05) mRNA levels at 24 hours. There were
      greater reductions in T-bet (P = 0.03) mRNA levels and lesser increases in
      TNFalpha (P = 0.015) and IFNgamma (P = 0.035) at 24 hours in those transfused.
      Multiple regression models confirmed that the transfusion of blood products was
      independently associated with altered patterns of gene expression. Blood stream
      infections occur in 15 (20.8%) of those transfused in the first 24 hours,
      compared with 1 patient (2.5%) not transfused (OR = 10.3 [1.3-81], P = 0.008).
      CONCLUSIONS: The primarily immunosuppressive inflammatory response to polytrauma
      may be exacerbated by the transfusion of blood products. Furthermore, transfusion
      was associated with an increased susceptibility to nosocomial infections.

PMID- 24670849
TI  - Systematic review of learning curves for minimally invasive abdominal surgery: a
      review of the methodology of data collection, depiction of outcomes, and
      statistical analysis.
AB  - OBJECTIVE: To determine how minimally invasive surgical learning curves are
      assessed and define an ideal framework for this assessment. BACKGROUND: Learning
      curves have implications for training and adoption of new procedures and devices.
      In 2000, a review of the learning curve literature was done by Ramsay et al and
      it called for improved reporting and statistical evaluation of learning curves.
      Since then, a body of literature is emerging on learning curves but the
      presentation and analysis vary. METHODS: A systematic search was performed of
      MEDLINE, EMBASE, ISI Web of Science, ERIC, and the Cochrane Library from 1985 to
      August 2012. The inclusion criteria are minimally invasive abdominal surgery
      formally analyzing the learning curve and English language. 592 (11.1%) of the
      identified studies met the selection criteria. RESULTS: Time is the most commonly
      used proxy for the learning curve (508, 86%). Intraoperative outcomes were used
      in 316 (53%) of the articles, postoperative outcomes in 306 (52%), technical
      skills in 102 (17%), and patient-oriented outcomes in 38 (6%) articles. Over
      time, there was evidence of an increase in the relative amount of laparoscopic
      and robotic studies (P < 0.001) without statistical evidence of a change in the
      complexity of analysis (P = 0.121). CONCLUSIONS: Assessment of learning curves is
      needed to inform surgical training and evaluate new clinical procedures. An ideal
      analysis would account for the degree of complexity of individual cases and the
      inherent differences between surgeons. There is no single proxy that best
      represents the success of surgery, and hence multiple outcomes should be
      collected.

PMID- 24670850
TI  - Reply to Letter: "Laparoscopic Retroperitoneal Hepatectomy: What Are the
      Indications?".

PMID- 24670851
TI  - Reply to letter: "The LAFA study".

PMID- 24670852
TI  - Reply to Letter: "Equivalence Approach Is More Appropriate for Comparison of
      Treatment Effect Estimates".

PMID- 24670853
TI  - Reply to Letter: "The Role of Surgery for Patients With a Complete Clinical
      Response After Chemoradiation for Esophageal Cancer".

PMID- 24670854
TI  - Poorer Survival for Stage IIa Patients After Minimally Invasive Esophagectomy.

PMID- 24670855
TI  - A systematic review of economic evaluations of enhanced recovery pathways for
      colorectal surgery.

PMID- 24670856
TI  - Operating room fire prevention: creating an electrosurgical unit fire safety
      device.
AB  - OBJECTIVE: To reduce the incidence of surgical fires. BACKGROUND: Operating room
      fires represent a potentially life-threatening hazard and are triggered by the
      electrosurgical unit (ESU) pencil. Carbon dioxide is a fire suppressant and is a
      routinely used medical gas. We hypothesize that a shroud of protective carbon
      dioxide covering the tip of the ESU pencil displaces oxygen, thereby preventing
      fire ignition. METHODS: Using 3-dimensional modeling techniques, a polymer sleeve
      was created and attached to an ESU pencil. This sleeve was connected to a carbon
      dioxide source and directed the gas through multiple precisely angled ports,
      generating a cone of fire-suppressive carbon dioxide surrounding the active
      pencil tip. This device was evaluated in a flammability test chamber containing
      21%, 50%, and 100% oxygen with sustained ESU activation. The sleeve was tested
      with and without carbon dioxide (control) until a fuel was ignited or 30 seconds
      elapsed. Time to ignition was measured by high-speed videography. RESULTS: Fires
      were ignited with each control trial (15/15 trials). The control group median +/-
      SD ignition time in 21% oxygen was 3.0 +/- 2.4 seconds, in 50% oxygen was 0.1 +/-
      1.8 seconds, and in 100% oxygen was 0.03 +/- 0.1 seconds. No fire was observed
      when the fire safety device was used in all concentrations of oxygen (0/15
      trials; P < 0.0001). The exact 95% confidence interval for absolute risk
      reduction of fire ignition was 76% to 100%. CONCLUSIONS: A sleeve creating a cone
      of protective carbon dioxide gas enshrouding the sparks from an ESU pencil
      effectively prevents fire in a high-flammability model. Clinical application of
      this device may reduce the incidence of operating room fires.

PMID- 24670857
TI  - Ghrelin protects rats against traumatic brain injury and hemorrhagic shock
      through upregulation of UCP2.
AB  - OBJECTIVE: To determine the mechanism responsible for ghrelin's neuroprotective
      effects after traumatic brain injury (TBI) and hemorrhagic shock. BACKGROUND:
      Ghrelin, a gastrointestinal hormone, has been demonstrated to possess multiple
      functions, including upregulation of uncoupling protein 2 (UCP2) and stimulation
      of the vagus nerve. Recent evidence has indicated that ghrelin is
      neuroprotective. We, therefore, hypothesized that ghrelin protects rats against
      TBI and hemorrhagic shock through upregulation of UCP2, involving stimulation of
      the vagus nerve. METHODS: Brain injury was induced by dropping a 450 g of weight
      from 1.5 m onto a steel helmet attached to the skull of male adult rats.
      Immediately after TBI, a midline laparotomy was performed, and both lumbar veins
      were isolated and severed at the junction with the vena cava. The abdomen was
      kept open for 20 minutes. At 45 minutes after TBI and uncontrolled hemorrhage
      (UH), ghrelin (4, 8, or 16 nmol/rat) or 1 mL of normal saline (vehicle) was
      intravenously administered. The Neurological Severity Scale (NSS), morphological
      alterations and beta-amyloid precursor protein expression in the brain, systemic
      organ injury markers (ie, alanine aminotransferase, aspartate aminotransferase,
      and lactate), and UCP2 expression in the cortex were measured. To determine
      whether the protective effect of ghrelin is mediated through upregulation of
      UCP2, genipin, a specific UCP2 antagonist, was administered intravenously before
      the injection of ghrelin in animals with TBI and UH. The role of the vagus nerve
      was assessed by performing vagotomy immediately before ghrelin administration.
      RESULTS: Ghrelin attenuated brain injury and facilitated functional recovery
      after TBI and UH. Ghrelin increased UCP2 expression in the cortex, and
      administration of genipin abolished ghrelin's protection after TBI and UH.
      Furthermore, vagotomy prevented the beneficial effects of ghrelin and eliminated
      ghrelin-induced UCP2 upregulation after TBI and UH. CONCLUSIONS: The protective
      effects of ghrelin after TBI and UH seem to be related to upregulation of UCP2
      expression in the brain and requiring the intact vagus nerve.

PMID- 24670859
TI  - Reply to Letter: "Preoperative Gemcitabine-Based Chemoradiation Therapy for
      Resectable and Borderline Resectable Pancreatic Cancer".

PMID- 24670858
TI  - Pretrauma center red blood cell transfusion is associated with reduced mortality
      and coagulopathy in severely injured patients with blunt trauma.
AB  - OBJECTIVE: To evaluate the association of pretrauma center (PTC) red blood cell
      (RBC) transfusion with outcomes in severely injured patients. BACKGROUND:
      Hemorrhage remains a major driver of mortality. Little evidence exists supporting
      PTC interventions to mitigate this. METHODS: Blunt injured patients in shock
      arriving at a trauma center within 2 hours of injury were included from the Glue
      Grant database. Subjects were dichotomized by PTC RBC transfusion. Outcomes
      included 24-hour mortality, 30-day mortality, and trauma-induced coagulopathy
      [(TIC), admission international normalized ratio >1.5]. Cox regression and
      logistic regression determined the association of PTC RBC transfusion with
      outcomes. To address baseline differences, propensity score matching was used.
      RESULTS: Of 1415 subjects, 50 received PTC RBC transfusion. Demographics and
      injury severity score were similar. The PTC RBC group received 1.3 units of RBCs
      (median), and 52% were scene transports. PTC RBC transfusion was associated with
      a 95% reduction in odds of 24-hour mortality [odds ratio (OR) = 0.05; 95%
      confidence interval (CI), 0.01-0.48; P < 0.01], 64% reduction in the risk of 30
      day mortality [hazard ratio = 0.36; 95% CI, 0.15-0.83; P = 0.02], and 88%
      reduction in odds of TIC (OR = 0.12; 95% CI, 0.02-0.79; P = 0.03). The matched
      cohort included 113 subjects (31% PTC RBC group). Baseline characteristics were
      similar. PTC RBC transfusion was associated with a 98% reduction in odds of 24
      hour mortality (OR = 0.02; 95% CI, 0.01-0.69; P = 0.04), 88% reduction in the
      risk of 30-day mortality (hazard ratio = 0.12; 95% CI, 0.03-0.61; P = 0.01), and
      99% reduction in odds of TIC (OR = 0.01; 95% CI, 0.01-0.95; P = 0.05).
      CONCLUSIONS: PTC RBC administration was associated with a lower risk of 24-hour
      mortality, 30-day mortality, and TIC in severely injured patients with blunt
      trauma, warranting further prospective study.

PMID- 24670860
TI  - Effect of Simvastatin on Physiological and Biological Outcomes in Patients
      Undergoing Esophagectomy: A Randomized Placebo-controlled Trial.

PMID- 24670861
TI  - Staging Laparoscopy Is Not the Best Option to Identify Unresectable Gallbladder
      Cancer With 100% of Accuracy.

PMID- 24670862
TI  - Reply to letter: "Single incision laparoscopic surgery for colorectal cancer".

PMID- 24670863
TI  - The aging surgeon.

PMID- 24670864
TI  - Results and factors affecting early outcome of fenestrated and/or branched stent
      grafts for aortic aneurysms: a multicenter prospective study.
AB  - OBJECTIVE: To present results and to identify predictive factors of early outcome
      after fenestrated and/or branched endovascular repair (f/b-EVAR) for complex
      aortic aneurysms, abdominal (AAA) and thoracoabdominal (TAAA). BACKGROUND:
      Feasibility of f/b-EVAR for complex aneurysms is now established, but little is
      known about which patients will benefit from this technique. METHODS: Univariate
      and multivariate analysis of preoperative and intraoperative factors on
      postoperative mortality and complications was performed on 268 patients (group 1:
      juxta- and pararenal AAA; group 2: suprarenal and TAAA IV; group 3: TAAA I, II,
      III) enrolled in a prospective multicenter trial of f/b-EVAR. RESULTS: Thirty-day
      mortality, in-hospital mortality (IM), and combined mortality and severe
      complications (CMSC) rates were 6.7%, 10.1%, and 22.0%, respectively. Group
      belonging (2 or 3 vs 1) was the only preoperative predictive factor of CMSC
      [hazard ratio (HR) = 2.10; 95% confidence interval (CI): 1.26-3.48; P = 0.0043].
      Occurrence of a technical complication and duration of intervention significantly
      influenced both IM (HR = 4.39; 95% CI: 2.05-9.38; P = 0.0001) and CMSC (HR =
      3.07; 95% CI: 1.84-5.11; P < 0.0001). Postoperative events associated with
      increased IM were spinal cord ischemia (HR = 9.46; 95% CI: 3.98-22.47; P <
      0.0001), hemodialysis (HR = 27.44; 95% CI: 12.63-59.61; P < 0.0001), and
      reintervention (HR = 4.45; 95% CI: 2.03-9.73; P = 0.0002). CONCLUSIONS: Although
      promising, f/b-EVAR still carries a significant rate of mortality and
      complications, mostly related to the complexity of the procedure. In these
      complex cases, new strategies should be investigated to improve outcomes.

PMID- 24670865
TI  - Survival from burns in the new millennium: 70 years' experience from a single
      institution.
AB  - OBJECTIVE: This review explores the series of published analyses from
      Massachusetts General Hospital to better understand how changes in medical
      specialization of burn medicine likely enabled the most important increase in
      survival from burns in the past 70 years. BACKGROUND: Seventy years ago, survival
      from the most serious burn injuries was not possible even in the most advanced
      countries until critical advances were introduced. Insights into those few
      medical advances that actually impacted survival might be better understood from
      the consideration of a continuous series of survival analyses over 7 decades at
      Massachusetts General Hospital. METHODS: Mortality data from previously reported
      probit and logit analyses from thousands of patients treated at Massachusetts
      General Hospital were reviewed. A comparison of mortality from these prior
      mortality analyses from a more recent multicenter study and a national data set
      was performed. RESULTS: The only giant leap forward in survival occurred during
      the 1970s, with no improvement during either the preceding or subsequent 30-year
      intervals. Despite the many modern advances that have been added to the care of
      these patients since 1984, although these may have represented medical progress,
      these advances did not impact survival. CONCLUSIONS: Survival rates from burn
      injury may have been maximized by current treatment approaches within medical
      centers of excellence in burn medicine. Further efforts to improve the quality of
      life of survivors of burn injury should ultimately have very favorable impact
      upon the long-term outcomes in these patients who now survive such devastating
      injuries.

PMID- 24670866
TI  - Highly efficient and recyclable carbon soot sponge for oil cleanup.
AB  - Carbon soot (CS) has the advantages of cost-effectiveness and production
      scalability over other carbons (i.e., graphene, CNTs) in their synthesis.
      However, little research has been conducted to explore the potential applications
      of CS. In this study, we demonstrated that a common daily waste-CS-can be used
      for developing a cost-effective absorbent (CS-sponge) to remove oil contaminants
      from water. The CS was synthesized by an ethylene-oxygen combustion flame. The CS
      sponge was prepared via a dip-coating method. Without further surface
      modification and pretreatments, the CS-sponge demonstrates high absorption
      capacities (up to 80 times its own weight) for a broad spectrum of oils and
      organic solvents with a recyclability of more than 10 times. These research
      results show evidence that the CS-sponge is promising in environmental
      remediation for large-scale, low-cost removal of oils from water. 

PMID- 24670867
TI  - Immune response to Haemonchus contortus and Haemonchus placei in sheep and its
      role on parasite specificity.
AB  - Two trials were conducted to determine the prepatent and the patent period of
      Haemonchus contortus and Haemonchus placei in Santa Ines crossbred sheep and to
      determine whether serial infections with both species confer protection against
      homologous or heterologous challenge. To evaluate the prepatent and patent
      periods of infection, five lambs received a single infection with 4000 H.
      contortus-infective larvae (L3), and another five received a single infection
      with 4000 H. placei L3. H. contortus presented patency earlier than H. placei.
      Animals infected with both species shed a large number of eggs in the faeces for
      several months with the highest counts, with means higher than 3000 eggs per gram
      of faeces (EPG) between 24 and 106 days and between 38 and 73 days post infection
      with H. contortus and H. placei, respectively. H. contortus eggs were detected in
      the faeces for a minimum of 302 days and a maximum of 538 days post infection,
      while the H. placei patent period lasted from 288 to 364 days. In the second
      trial, one group of lambs (n=12) was serially infected 12 times (three times per
      week for four weeks) with 500 L3 of H. placei and then challenged with either H.
      placei (n=6) or with H. contortus (n=6). The lambs in the second group (n=12)
      were serially infected 12 times with 500 L3 of H. contortus and then challenged
      with H. contortus (n=6) or with H. placei (n=6), and a third group of lambs was
      single challenged with H. placei (n=6), H. contortus (n=6), or remained
      uninfected throughout the trial period (control group, n=6). Animals serially
      infected with H. placei and then challenged with the same species presented the
      most intense immune response with the highest levels of anti-parasitic
      immunoglobulin and number of inflammatory cells in the abomasal mucosa. As a
      result, this group had the lowest rate of parasite establishment (2.68% of the
      4000 L3 given), but this phenomenon did not occur in animals single challenged
      with H. placei, in which the rate of establishment was relatively high (25.3%),
      confirming that the protective immune response to H. placei develops only when
      animals are repeatedly infected with this species. However, when the animals were
      previously serially infected with H. placei and then challenged with H.
      contortus, no evidence of significant protection was observed (establishment of
      19.18%). The results of the trials showed an important role played by the immune
      response on parasite-host specificity. 

PMID- 24670868
TI  - Plasmonic Ag deposited TiO2 nano-sheet film for enhanced photocatalytic hydrogen
      production by water splitting.
AB  - TiO2 nano-sheet film (TiO2 NSF) was prepared by a hydrothermal method. Ag
      nanoparticles (NPs) were then deposited on the surface of TiO2 NSF (Ag/TiO2 NSF)
      under microwave-assisted chemical reduction. The prepared samples were
      characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM), UV
      visible (UV-vis) absorption spectroscopy, x-ray photoelectron spectroscopy (XPS),
      photoluminescence (PL) spectroscopy, and Raman scattering spectroscopy. The
      results revealed that the Ag NPs were well dispersed on the anatase/rutile mixed
      phase TiO2 nano-sheet surface with a metallic state. The visible light absorption
      and Raman scattering of TiO2 were enhanced by Ag NPs based on its surface plasmon
      resonance effect. Besides, Ag NPs could also effectively restrain the
      recombination of photogenerated electrons and holes. Photocatalytic water
      splitting was conducted on the films to obtain hydrogen, and the experimental
      results indicated that plasmonic Ag NPs could greatly enhance the photocatalytic
      activity of TiO2 due to the synergistic effect between electron transfer and
      surface plasmon resonance enhanced absorption. The hydrogen yield obtained from
      the optimal sample reached 8.1 MUmol cm(-2) and the corresponding energy
      efficiency was about 0.47%, which was 8.5 times higher than that of pure TiO2
      film. Additionally, the formation mechanism of TiO2 nano-sheet film is
      preliminarily discussed. 

PMID- 24670870
TI  - Overdetection in screening for prostate cancer.
AB  - PURPOSE OF REVIEW: To describe mechanisms behind and extent of overdetection in
      prostate cancer screening as well as possible ways to avoid unnecessary
      overdiagnosis. RECENT FINDINGS: Overdetection and overtreatment is common in many
      areas of modern medicine. Current prostate-specific antigen (PSA) testing has
      resulted in a marked stage shift to early stages, which, together with
      improvements in treatment, has resulted in a substantial decrease in prostate
      cancer mortality. However, nonselective, widespread PSA-testing followed by
      liberal biopsy criteria has resulted in a high rate of overdiagnosis, which
      constitutes one major obstacle to introducing population-based screening.
      SUMMARY: Several steps are needed to decrease overdetection: do not screen
      elderly men unlikely to benefit, do not biopsy without a compelling reason,
      differentiate screening interval according to risk, work-up benign prostate
      disease by using reflex tests and/or complementary biomarkers, and focus on
      screening men at high risk for a life-threatening disease, for example evaluate
      men with above-median PSA levels in midlife. Recent results indicate that use of
      MRI to select men for biopsy and using only lesion-directed biopsies may be one
      way forward. However, more studies are needed before firm recommendations can be
      made. When the diagnosis is made, treat only those who need treatment. Tailor
      treatment to tumor biology and patient characteristics, and offer active
      surveillance to eligible men with low-risk tumors, especially small-volume
      disease, as the first management.

PMID- 24670869
TI  - Joint effects of colorectal cancer susceptibility loci, circulating 25
      hydroxyvitamin D and risk of colorectal cancer.
AB  - BACKGROUND: Genome wide association studies (GWAS) have identified several SNPs
      associated with colorectal cancer (CRC) susceptibility. Vitamin D is also
      inversely associated with CRC risk. METHODS: We examined main and joint effects
      of previously GWAS identified genetic markers of CRC and plasma 25-hydroxyvitamin
      D (25(OH)D) on CRC risk in three prospective cohorts: the Nurses' Health Study
      (NHS), the Health Professionals Follow-up Study (HPFS), and the Physicians'
      Health Study (PHS). We included 1895 CRC cases and 2806 controls with genomic
      DNA. We calculated odds ratios and 95% confidence intervals for CRC associated
      with additive genetic risk scores (GRSs) comprised of all CRC SNPs and subsets of
      these SNPs based on proximity to regions of increased vitamin D receptor binding
      to vitamin D response elements (VDREs), based on published ChiP-seq data. Among a
      subset of subjects with additional prediagnostic 25(OH)D we tested multiplicative
      interactions between plasma 25(OH)D and GRS's. We used fixed effects models to
      meta-analyze the three cohorts. RESULTS: The per allele multivariate OR was 1.12
      (95% CI, 1.06-1.19) for GRS-proximalVDRE; and 1.10 (95% CI, 1.06-1.14) for GRS
      nonproxVDRE. The lowest quartile of plasma 25(OH)D compared with the highest, had
      a multivariate OR of 0.63 (95% CI, 0.48-0.82) for CRC. We did not observe any
      significant interactions between any GRSs and plasma 25(OH)D. CONCLUSIONS: We did
      not observe evidence for the modification of genetic susceptibility for CRC
      according to vitamin D status, or evidence that the effect of common CRC risk
      alleles differed according to their proximity to putative VDR binding sites.

PMID- 24670871
TI  - Biopsy strategies for selecting patients for focal therapy for prostate cancer.
AB  - PURPOSE OF REVIEW: Focal therapy for localised prostate cancer requires accurate
      disease localization and characterization. Standard trans-rectal ultrasound
      biopsy can miss significant cancer and cannot accurately localize prostate cancer
      to guide focal therapy. This article examines various biopsy and imaging
      strategies to determine which is the most useful in diagnosing prostate cancer
      suitable for treatment with focal therapy. RECENT FINDINGS: Advances in MRI and
      ultrasound have been combined with different biopsy techniques such as
      transperineal and targeted biopsy versus transrectal and whole-gland sampling to
      see which method detects and localizes cancer while reducing the burden of biopsy
      on patients. SUMMARY: Studies tended to report on overall cancer detection rates
      as opposed to clinically significant cancer detection rates. A standard
      definition of clinically significant cancer must first be defined and validated
      against an accurate sampling strategy such as radical prostatectomy or
      transperineal prostate mapping biopsy. Image-guided targeted biopsy has increased
      detection rates of clinically significant cancer rate with fewer number of cores
      compared with whole-gland sampling. Further prospective randomized controlled
      trials are needed to identify a combined image and biopsy technique that detects
      and localizes the highest rate of clinically significant cancer while decreasing
      the risk to patients, in order to guide focal therapy.

PMID- 24670873
TI  - siRNA targeting prohibitins inhibits proliferation and promotes apoptosis of
      gastric carcinoma cell line SGC7901 in vitro and in vivo.
AB  - In the present study we investigate the effects of small interfering RNA (siRNA)
      mediated silencing of prohibitins (Phbs) gene expressions on gastric carcinoma
      cell proliferation and apoptosis in vitro and in vivo. Firstly, Phbs proteins in
      five human gastric carcinoma cell lines were evaluated by Western blotting. Then
      three siRNA sequences targeting Phbs were designed and transfected into the
      cancer cell line with the highest Phbs protein expressions. The cell
      proliferation and apoptosis were analyzed by MTT and flow cytometry methods. In
      vivo, the effects of siRNAs on the proliferation and apoptosis were assayed in
      xenografted tumors of nude mice. Phbs proteins were expressed highest in gastric
      carcinoma cell line SGC7901. The cell proliferation significantly decreased upon
      Phbs silencing. The cell percentage in S phase was significantly lower in Phbs
      silenced groups, and the apoptotic cell ratio was significantly higher. siRNA
      targeting Phbs significantly inhibited the growth of the xenografted tumors.
      Further, Bcl-2 and Bax was respectively downregulated and upregulated after the
      Phbs silencing in the xenografted tumors. Caspase-3 and caspase-9 activities were
      significantly enhanced in the Phbs-silenced tumors. In summary, siRNA-mediated
      silencings of Phbs inhibit proliferation and promotes apoptosis of gastric
      carcinoma cells SGC7901 in vitro and in vivo, suggesting key roles of Phbs in the
      development of SGC7901 cell line.

PMID- 24670872
TI  - SLC7A14 linked to autosomal recessive retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is characterized by degeneration of the retinal
      photoreceptors and is the leading cause of inherited blindness worldwide.
      Although few genes are known to cause autosomal recessive RP (arRP), a large
      proportion of disease-causing genes remain to be revealed. Here we report the
      identification of SLC7A14, a potential cationic transporter, as a novel gene
      linked to arRP. Using exome sequencing and direct screening of 248 unrelated
      patients with arRP, we find that mutations in the SLC7A14 gene account for 2% of
      cases of arRP. We further demonstrate that SLC7A14 is specifically expressed in
      the photoreceptor layer of the mammalian retina and its expression increases
      during postnatal retinal development. In zebrafish, downregulation of slc7a14
      expression leads to an abnormal eye phenotype and defective light-induced
      locomotor response. Furthermore, targeted knockout of Slc7a14 in mice results in
      retinal degeneration with abnormal ERG response. This suggests that SLC7A14 has
      an important role in retinal development and visual function. 

PMID- 24670874
TI  - Medieval horse stable; the results of multi proxy interdisciplinary research.
AB  - A multi proxy approach was applied in the reconstruction of the architecture of
      Medieval horse stable architecture, the maintenance practices associated with
      that structure as well as horse alimentation at the beginning of 13th century in
      Central Europe. Finally, an interpretation of the local vegetation structure
      along Morava River, Czech Republic is presented. The investigated stable
      experienced two construction phases. The infill was well preserved and its
      composition reflects maintenance practices. The uppermost part of the infill was
      composed of fresh stabling, which accumulated within a few months at the end of
      summer. Horses from different backgrounds were kept in the stable and this is
      reflected in the results of isotope analyses. Horses were fed meadow grasses as
      well as woody vegetation, millet, oat, and less commonly hemp, wheat and rye.
      Three possible explanations of stable usage are suggested. The stable was
      probably used on a temporary basis for horses of workers employed at the castle,
      courier horses and horses used in battle. 

PMID- 24670875
TI  - Herceptin resistance database for understanding mechanism of resistance in breast
      cancer patients.
AB  - Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for
      Her2-positive breast cancer patients. However, it is not effective against
      several patients due to acquired or de novo resistance. In last one decade,
      several assays have been performed to understand the mechanism of Herceptin
      resistance with/without supplementary drugs. This manuscript describes a database
      HerceptinR, developed for understanding the mechanism of resistance at genetic
      level. HerceptinR maintains information about 2500 assays performed against
      various breast cancer cell lines (BCCs), for improving sensitivity of Herceptin
      with or without supplementary drugs. In order to understand Herceptin resistance
      at genetic level, we integrated genomic data of BCCs that include expression,
      mutations and copy number variations in different cell lines. HerceptinR will
      play a vital role in i) designing biomarkers to identify patients eligible for
      Herceptin treatment and ii) identification of appropriate supplementary drug for
      a particular patient. HerceptinR is available at
      http://crdd.osdd.net/raghava/herceptinr/. 

PMID- 24670877
TI  - Cardiac tamponade.

PMID- 24670878
TI  - Impact of endovascular therapy on oxidative stress in patients with peripheral
      artery disease.
AB  - BACKGROUND: Atherosclerosis is believed to be caused by oxidative stress.
      Endovascular therapy (EVT) is effective for claudication of patients with
      peripheral artery disease (PAD). However, its effect on oxidative stress in PAD
      patients is unknown. Here, the impact of EVT on oxidative stress in PAD patients
      is investigated. METHODS AND RESULTS: Twenty-five PAD patients (Rutherford stage
      II or III) who underwent EVT were enrolled. The levels of diacron-reactive oxygen
      metabolite (d-ROM; an oxidative stress marker), ankle-brachial index (ABI), and
      maximum walking distance at baseline and at 3 months after EVT were measured. As
      compared with baseline values, the maximum walking distance and ABI improved
      significantly after EVT (109.9+/-104.2 vs. 313.7+/-271.8m, P<0.0001; 0.61+/-0.15
      vs. 0.91+/-0.13m, P<0.0001, respectively). The improved exercise capacity and
      arterial flow induced a significant decrease in d-ROM levels (from 472.8+/-64.8
      to 390.2+/-46.7U.CARR; P<0.0001). The decrease in d-ROM levels after EVT was more
      prominent in PAD patients with a high baseline d-ROM level. The increased ABI
      (r=0.524, P=0.0007) and maximum walking distance (r=-0.416, P=0.039) after EVT
      were significantly correlated with the decreased d-ROM levels. CONCLUSIONS: The
      improved exercise capacity and peripheral blood flow induced by EVT decreases
      oxidative stress in PAD patients.

PMID- 24670876
TI  - Discovery and characterization of olokizumab: a humanized antibody targeting
      interleukin-6 and neutralizing gp130-signaling.
AB  - Interleukin-6 (IL-6) is a critical regulator of the immune system and has been
      widely implicated in autoimmune disease. Here, we describe the discovery and
      characterization of olokizumab, a humanized antibody to IL-6. Data from
      structural biology, cell biology and primate pharmacology demonstrate the
      therapeutic potential of targeting IL-6 at "Site 3", blocking the interaction
      with the signaling co-receptor gp130. 

PMID- 24670879
TI  - Impact of concomitant surgical atrial fibrillation ablation in patients
      undergoing aortic valve replacement.
AB  - BACKGROUND: The clinical benefit of concomitant atrial fibrillation (AF) ablation
      at the time of aortic valve replacement (AVR) is uncertain. METHODS AND RESULTS:
      A total of 124 patients with AF who underwent AVR with (n=50) or without (n=74) a
      concomitant maze procedure, between 2000 and 2011, were evaluated. There were no
      significant differences in early postoperative outcomes. During a median clinical
      follow-up of 18.1 months (interquartile range: 6.9-47.8 months), 19 late deaths
      (15.3%) and 33 valve-related complications (26.6%) occurred, but the differences
      between groups were not statistically significant. Major event-free survival at 5
      years was 60.9+/-9.9% vs. 57.0+/-10.3% (P=0.41). After adjustment, the maze group
      demonstrated similar risks for major adverse cardiac events (hazard ratio, 1.18;
      95% confidence interval, 0.56-2.49; P=0.67). However, the rate of sinus rhythm
      restoration at 4 years was significantly higher in the maze group (80.6% vs.
      3.6%, P<0.001). Left atrial dimension was smaller (46.9 vs. 50.4mm, P=0.017), and
      the ejection fraction was higher (60.6% vs. 58.0%, P=0.059) in the maze group.
      The rate of postoperative anticoagulation was also lower in the maze group (53.1%
      vs. 89.2%, P<0.001). CONCLUSIONS: Concomitant AF ablation in patients undergoing
      AVR resulted in increased sinus rhythm restoration, better echocardiographic
      results, and decreased anticoagulation requirement, without increasing surgical
      morbidity or mortality.

PMID- 24670880
TI  - Does the kidney injury molecule-1 predict cisplatin-induced kidney injury in
      early stage?
AB  - BACKGROUND: It is not possible to diagnose acute kidney injury (AKI) in early
      stages with traditional biomarkers. Kidney injury molecule-1 (KIM-1) is a novel
      biomarker promising the diagnosis of AKI in early stages. We studied whether
      urinary and serum KIM-1 (KIM-1 U and KIM-1 S ) concentrations were useful in
      predicting cisplatin-induced AKI in early stages. METHODS: We prospectively
      analysed 22 patients on cisplatin treatment. KIM-1 S and KIM-1 U concentrations
      were assessed in the samples of the patients on four different time periods
      (before treatment [BT], first [AT1], third [AT3] and fifth [AT5] day after
      treatment). RESULTS: KIM-1 U concentrations on the first day after cisplatin
      treatment in patients with AKI were significantly increased compared to both KIM
      1 U concentrations of the same patients BT (P=0.009) and to AT1-KIM-1 U
      concentrations of the patients without AKI (P=0.008). A receiver operating
      characteristic analysis revealed that AT1-KIM-1 U concentrations may predict AKI
      with an 87.5% sensitivity and 93.3% specificity (area under the curve=0.94). KIM
      1 S concentrations were not significantly changed between BT and AT periods.
      CONCLUSIONS: KIM-1 U concentrations may predict cisplatin-induced AKI in early
      stages with high sensitivity and specificity.

PMID- 24670882
TI  - Erratum.

PMID- 24670881
TI  - Predictors of long-term mortality in patients with cirrhosis undergoing cardiac
      surgery.
AB  - AIM: Little is known regarding the long-term outcome in cirrhotic patients
      undergoing cardiac surgery. The objective of this study was to identify
      preoperative and postoperative mortality risk factors and to determine the best
      predictors of long-term outcome. METHODS: Fifty-eight consecutive cirrhotic
      patients requiring cardiac surgery between January 2004 and January 2009 were
      prospectively studied at our institution. Seven patients (12%) died. A complete
      follow-up was performed in the whole survival group until November 2012 (mean
      46+/-28 months). Variables usually measured on admission and during the first 24
      h of the postoperative period were evaluated together with cardiac surgery scores
      (Parsonnet, EuroSCORE), liver scores (Child-Turcotte-Pugh, Model for End-Stage
      Liver Disease, United Kingdom End-Stage Liver Disease score), and ICU scores
      (Acute Physiology and Chronic Health Evaluation II and III, Simplified Acute
      Physiology Score II and III, Sequential Organ Failure Assessment). RESULTS:
      Twelve patients (23.5%) died during follow-up; six were Child class A and six
      class B. Comparing survivors vs. non-survivors using univariate analysis,
      variables associated with better long-term outcome were lower arterial lactate 24
      h after admission (1.7+/-0.4 vs. 2.1+/-0.7 mmol.L(-1), P=0.03) and higher urine
      output in the first 24 h (2029+/-512 vs. 1575+/-627 mL, P=0.03). The receiver
      operating characteristic curve showed that the Simplified Acute Physiology Score
      III score had the best predictive value for long-term outcome (AUC: 77.4+/-0.76%;
      sensitivity: 83.3%; specificity: 64.9%, P=0.005). Multivariate analysis
      identified Simplified Acute Physiology Score III score (P=0.02) and urine output
      in the first 24 h (P=0.02) as independent factors associated with long-term
      outcome. Long-term survival was 82.4% for Child A, 47.6% for Child B and 33.3%
      for Child C (P=0.001). CONCLUSION: Long-term survival in cirrhotic patients
      requiring cardiac surgery is a more valuable prognostic measure than short-term
      survival. Urine output in the first 24 h may be a valuable predictor of long-term
      outcome in these patients. The Simplified Acute Physiology Score III is also
      useful.

PMID- 24670883
TI  - Erratum.

PMID- 24670884
TI  - Postural adaptation during arm raising in children with and without unilateral
      cerebral palsy.
AB  - Postural sway during arm movements were related to the size of the base of
      support (BOS) and the limits of stability (LOS) of children with unilateral
      cerebral palsy (USCP) and typically developing (TD) children. For half of the
      trials the mechanical disturbance due to the rapid arm movement was increased by
      attaching small weights at the wrists. The participants stood with both feet on a
      large force plate, which recorded the displacements of the center of pressure
      (CoP). The results showed that in the children with USCP the LOS forward and
      toward the non-dominant (more-affected) side were smaller than in the TD children
      whereas the LOS backward and toward the dominant (less-affected) side did not
      differ between the two groups. When rapidly moving the arms the children with
      USCP swayed over a larger portion of their base of support in the forward
      direction and toward their more-affected side. In addition, the maximal sway
      toward the more-affected side during arm movement exceeded the LOS while balance
      was maintained. These effects increased when the movements were performed with
      the weights at the wrists. These results show that an area of permissible sway,
      which was not spontaneously explored during the leaning task, was required to
      maintain balance during the supra-postural task. Training to enlarge the LOS that
      includes weight shifts toward the more-affected side might reduce the area of the
      BOS that is self-perceived as less secure.

PMID- 24670885
TI  - Management of neonates born to women with Graves' disease: a cohort study.
AB  - OBJECTIVE: Hyperthyroidism in neonates born to mothers with Graves' disease (GD)
      can be associated with significant morbidity and mortality, but is still
      overlooked by clinicians. Management of neonatal hyperthyroidism would be
      improved by a better understanding of the predictive factors involved. The aim of
      this study was to evaluate the course of thyroid function and clinical outcomes
      during the first postnatal month in babies born to mothers with GD. DESIGN:
      Prospective observational study. METHODS: Sixty-eight neonates born to mothers
      with GD were managed from birth and divided into three groups based on
      thyrotropin receptor antibody (TRAb) and anti-thyroid drug (ATD) status in the
      mother: TRAb(-ve)/ATD(-ve), n=27; TRAb(-ve)/ATD(+) (ve), n=8; and
      TRAb(+ve)/ATD(+ve), n=33. The main outcome measures were clinical examination,
      thyroid function tests (TSH, free thyroxine (FT4), free triiodothyronine, and
      TRAb), echocardiography, thyroid ultrasonography, and bone maturation assessment.
      RESULTS: None of the infants born to TRAb(-ve) mothers with GD developed neonatal
      hyperthyroidism. Of the 33 TRAb(+ve)/ATD(+ve) neonates, 24 (72.7%) had positive
      TRAb on cord blood assays, and seven of these developed neonatal hyperthyroidism.
      FT4 elevation between days 3 and 7 but not at birth was predictive of the
      development of hyperthyroidism. CONCLUSIONS: TRAb status should be checked in the
      third trimester in mothers with GD and on cord blood in their neonates; if
      positive, it indicates a high risk of neonatal hyperthyroidism. FT4 measurement
      at birth should be repeated between days 3 and 5 (and by day 7 at the latest);
      rapid FT4 elevation during the first postnatal week is predictive of
      hyperthyroidism and warrants ATD therapy.

PMID- 24670886
TI  - Serum sex hormone-binding globulin and testosterone in relation to cardiovascular
      disease risk factors in young men: a population-based study.
AB  - OBJECTIVE: Reduced sex hormone-binding globulin (SHBG) concentration predicts
      insulin resistance and type 2 diabetes, but its association with cardiovascular
      disease (CVD) risk is unclear. We examined the association between SHBG and
      cardiovascular risk factors, independently of total testosterone (TT), in young
      men. DESIGN: Observational, cross-sectional study. SETTING: General community.
      PARTICIPANTS: The study included 2716 men aged 31 years in the Northern Finland
      Birth Cohort in 1996 with clinical examination data and fasting blood samples.
      OUTCOME VARIABLES: Blood pressure (BP), lipids and C-reactive protein (CRP) as
      biological CVD risk markers. RESULTS: SHBG concentration was significantly and
      inversely related to systolic and diastolic BP, triglycerides and CRP, but
      positively to HDL cholesterol after adjusting for insulin, BMI, waist
      circumference, smoking, education and physical activity (all P<0.05). These
      linearly graded associations persisted with additional adjustment for TT. SHBG
      was significantly associated with total cholesterol only with adjustment for
      covariates and TT (P<0.05). The direction and magnitude of associations between
      TT and risk factors were variable, but further adjustment for insulin, adiposity
      and SHBG showed positive associations between TT and BP, total and LDL
      cholesterol and triglycerides and an inverse association with CRP (all P<0.05),
      but its relation with HDL-cholesterol was no longer significant. CONCLUSIONS: In
      this cohort of young adult men, higher SHBG concentration was associated with a
      more favourable CVD risk profile, independently of TT. SHBG concentration
      modified the associations of TT with CVD risk factors.

PMID- 24670887
TI  - Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and
      posterior AD.
AB  - OBJECTIVE: To investigate association of genetic risk factors for late-onset
      Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a
      syndrome of visual impairment with predominant Alzheimer disease (AD) pathology
      in posterior cortical regions, and with risk of "posterior AD" neuropathology.
      METHODS: We assessed 81 participants with PCA diagnosed clinically and 54 with
      neuropathologic diagnosis of posterior AD vs 2,523 controls for association with
      11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk
      genome-wide association studies. RESULTS: There was highly significant
      association with APOE epsilon4 and increased risk of PCA (p = 0.0003, odds ratio
      [OR] = 3.17) and posterior AD (p = 1.11 * 10(-17), OR = 6.43). No other locus was
      significant after corrections for multiple testing, although rs11136000 near CLU
      (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated
      nominally significantly with posterior AD, and rs3851179 at the PICALM locus had
      significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP
      rs3764650, which was also tested under the recessive model because of Hardy
      Weinberg disequilibrium, also had nominally significant association with PCA
      risk. The direction of association at APOE, CLU, and BIN1 loci was the same for
      participants with PCA and posterior AD. The effects for all SNPs, except
      rs3851179, were consistent with those for LOAD risk. CONCLUSIONS: We identified a
      significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk
      loci for PCA and posterior AD. Our findings suggest that at least some of the
      genetic risk factors for LOAD are shared with these atypical conditions and
      provide effect-size estimates for their future genetic studies.

PMID- 24670888
TI  - Barriers to investigator-initiated deep brain stimulation and device research.
AB  - The success of device-based research in the clinical neurosciences has
      overshadowed a critical and emerging problem in the biomedical research
      environment in the United States. Neuroprosthetic devices, such as deep brain
      stimulation (DBS), have been shown in humans to be promising technologies for
      scientific exploration of neural pathways and as powerful treatments. Large
      device companies have, over the past several decades, funded and developed major
      research programs. However, both the structure of clinical trial funding and the
      current regulation of device research threaten investigator-initiated efforts in
      neurologic disorders. The current atmosphere dissuades clinical investigators
      from pursuing formal and prospective research with novel devices or novel
      indications. We review our experience in conducting a federally funded,
      investigator-initiated, device-based clinical trial that utilized DBS for
      thalamic pain syndrome. We also explore barriers that clinical investigators face
      in conducting device-based clinical trials, particularly in early-stage studies
      or small disease populations. We discuss 5 specific areas for potential reform
      and integration: (1) alternative pathways for device approval; (2) eliminating
      right of reference requirements; (3) combining federal grant awards with
      regulatory approval; (4) consolidation of oversight for human subjects research;
      and (5) private insurance coverage for clinical trials. Careful reformulation of
      regulatory policy and funding mechanisms is critical for expanding investigator
      initiated device research, which has great potential to benefit science,
      industry, and, most importantly, patients. 

PMID- 24670890
TI  - Stress and migraine: something expected, something unexpected.

PMID- 24670889
TI  - Reduction in perceived stress as a migraine trigger: testing the "let-down
      headache" hypothesis.
AB  - OBJECTIVE: To test whether level of perceived stress and reductions in levels of
      perceived stress (i.e., "let-down") are associated with the onset of migraine
      attacks in persons with migraine. METHODS: Patients with migraine from a tertiary
      headache center were invited to participate in a 3-month electronic diary study.
      Participants entered data daily regarding migraine attack experience, subjective
      stress ratings, and other data. Stress was assessed using 2 measures: the
      Perceived Stress Scale and the Self-Reported Stress Scale. Logit-normal, random
      effects models were used to estimate the odds ratio for migraine occurrence as a
      function of level of stress over several time frames. RESULTS: Of 22 enrolled
      participants, 17 (median age 43.8 years) completed >30 days of diaries, yielding
      2,011 diary entries including 110 eligible migraine attacks (median 5 attacks per
      person). Level of stress was not generally associated with migraine occurrence.
      However, decline in stress from one evening diary to the next was associated with
      increased migraine onset over the subsequent 6, 12, and 18 hours, with odds
      ratios ranging from 1.5 to 1.9 (all p values < 0.05) for the Perceived Stress
      Scale. Decline in stress was associated with migraine onset after controlling for
      level of stress for all time points. Findings were similar using the Self
      Reported Stress Scale. CONCLUSIONS: Reduction in stress from one day to the next
      is associated with migraine onset the next day. Decline in stress may be a marker
      for an impending migraine attack and may create opportunities for preemptive
      pharmacologic or behavioral interventions.

PMID- 24670891
TI  - rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic
      substrate.
AB  - OBJECTIVE: This double-blind, randomized, placebo-controlled study investigated
      the impact of repetitive transcranial magnetic stimulation (rTMS) on quality of
      life (QoL) of patients with fibromyalgia, and its possible brain metabolic
      substrate. METHODS: Thirty-eight patients were randomly assigned to receive high
      frequency rTMS (n = 19) or sham stimulation (n = 19), applied to left primary
      motor cortex in 14 sessions over 10 weeks. Primary clinical outcomes were QoL
      changes at the end of week 11, measured using the Fibromyalgia Impact
      Questionnaire (FIQ). Secondary clinical outcomes were mental and physical QoL
      component measured using the 36-Item Short Form Health Survey (SF-36), but also
      pain, mood, and anxiety. Resting-state [(18)F]-fluorodeoxyglucose-PET metabolism
      was assessed at baseline, week 2, and week 11. Whole-brain voxel-based analysis
      was performed to study between-group metabolic changes over time. RESULTS: At
      week 11, patients of the active rTMS group had greater QoL improvement in the FIQ
      (p = 0.032) and in the mental component of the SF-36 (p = 0.019) than the sham
      stimulation group. No significant impact was found for other clinical outcomes.
      Compared with the sham stimulation group, patients of the active rTMS group
      presented an increase in right medial temporal metabolism between baseline and
      week 11 (p < 0.001), which was correlated with FIQ and mental component SF-36
      concomitant changes (r = -0.38, p = 0.043; r = 0.51, p = 0.009, respectively).
      QoL improvement involved mainly affective, emotional, and social dimensions.
      CONCLUSION: Our study shows that rTMS improves QoL of patients with fibromyalgia.
      This improvement is associated with a concomitant increase in right limbic
      metabolism, arguing for a neural substrate to the impact of rTMS on emotional
      dimensions involved in QoL. CLASSIFICATION OF EVIDENCE: This study provides Class
      II evidence that rTMS compared with sham rTMS improves QoL in patients with
      fibromyalgia.

PMID- 24670892
TI  - Experience with the use of a partial ossicular replacement prosthesis with a ball
      and-socket joint between the plate and the shaft.
AB  - BACKGROUND: In the further development of alloplastic prostheses for use in
      middle ear surgery, the Dresden and Cologne University Hospitals, working
      together with a company, introduced a new partial ossicular replacement
      prosthesis in 2011. The ball-and-socket joint between the prosthesis and the
      shaft mimics the natural articulations between the malleus and incus and between
      the incus and stapes, allowing reaction to movements of the tympanic membrane
      graft, particularly during the healing process. STUDY DESIGN: Retrospective
      evaluation METHODS: To reconstruct sound conduction as part of a type III
      tympanoplasty, partial ossicular replacement prosthesis with a ball-and-socket
      joint between the plate and the shaft was implanted in 60 patients, with other
      standard partial ossicular replacement prosthesis implanted in 40 patients and 64
      patients. Pure-tone audiometry was carried out, on average, 19 and 213 days after
      surgery. Results of the partial ossicular replacement prosthesis with a ball-and
      socket joint between the plate and the shaft were compared with those of the
      standard prostheses. RESULTS: Early measurements showed a mean improvement of 3.3
      dB in the air-bone gap (ABG) with the partial ossicular replacement prosthesis
      with a ball-and-socket joint between the plate and the shaft, giving similar
      results than the standard implants (6.6 and 6.0 dB, respectively), but the
      differences were not statistically significant. Later measurements showed a
      statistically significant improvement in the mean ABG, 11.5 dB, compared with 4.4
      dB for one of the standard partial ossicular replacement prosthesis and a
      tendency of better results to 6.9 dB of the other standard prosthesis.
      CONCLUSIONS: In our patients, we achieved similarly good audiometric results to
      those already published for the partial ossicular replacement prosthesis with a
      ball-and-socket joint between the plate and the shaft. Intraoperative fixation
      posed no problems, and the postoperative complication rate was low.

PMID- 24670893
TI  - Electrolyte-induced reorganization of SDS self-assembly on graphene: a molecular
      simulation study.
AB  - A molecular dynamics simulation was conducted to study the structure and
      morphology of sodium dodecyl sulfate (SDS) surfactants adsorbed on a nanoscale
      graphene nanostructure in the presence of an electrolyte. The self-assembly
      structure can be reorganized by the electrolyte-induced effect. An increase in
      the ionic strength of the added electrolyte can enhance the stretching of
      adsorbed surfactants toward the bulk aqueous phase and make headgroups assemble
      densely, leading to a more compact structure of the SDS/graphene composite. The
      change in the self-assembly structure is attributed to the
      accumulation/condensation of electrolyte cations near the surfactant aggregate,
      consequently screening the electrostatic repulsion between charged headgroups.
      The role of the electrolyte revealed here provides direct microscopic evidence or
      an explanation of the reported experiments in the electrolyte tuning of the
      interfacial structure of a surfactant aggregate on the surface of carbon
      nanoparticles. Additionally, the buoyant density of the SDS/graphene assembly has
      been computed. With an increase in the ionic strength of the electrolyte, the
      buoyant density of the SDS/graphene composite rises. The interfacial accumulation
      of electrolytes provides an important contribution to the density enhancement.
      The study will be valuable for the dispersion and application of graphene
      nanomaterials. 

PMID- 24670894
TI  - Development and validation of a new multidimensional measure of inspiration:
      associations with risk for bipolar disorder.
AB  - BACKGROUND: Individuals at risk for, and diagnosed with, bipolar disorder (BD)
      appear to have heightened levels of creativity. Although inspiration is
      creativity, the ways in which individuals appraise and respond emotionally to
      inspiration in BD remain unexplored. METHOD: The present study reports on a new
      measure of inspiration (External and Internal Sources of Inspiration Scale-
      EISI). The reliability and validity of EISI were explored along with associations
      between EISI and BD risk. RESULTS: Among a cross-national student sample (N =
      708) 5 inspiration factors were derived from EISI (self, other, achievement,
      prosocial and external inspiration). Reliability, concurrent validity and
      convergent/divergent validity were good. Total EISI and all subscales were
      associated with increased positive rumination, and total EISI and the achievement
      EISI subscale were associated with impulsivity. Total EISI, self and prosocial
      EISI subscales were independently associated with BD risk and current mania
      symptoms. CONCLUSION: This new measure of inspiration is multidimensional,
      reliable and valid. Findings suggest that self and prosocial focused inspiration
      are particularly associated with risk for BD after controlling for current manic
      symptoms. Future studies in clinical populations may illuminate the relationships
      between inspiration and creativity in BD.

PMID- 24670895
TI  - Alkalibacillus almallahensis sp. nov., a halophilic bacterium isolated from an
      inland solar saltern.
AB  - A halophilic, Gram-staining-positive, non-motile, endospore forming rod-shaped
      bacterial strain, S1LM8(T), was isolated from a sediment sample collected from an
      inland solar saltern located in La Malaha, Granada (Spain). Growth was observed
      in media containing 7.5-30% total salts (optimum 15% total salts), at pH 7-10
      (optimum pH 8) and at 15-50  degrees C (optimum 35-38  degrees C). The
      predominant isoprenoid quinone was MK-7. It contained A1gamma-type peptidoglycan
      with meso-diaminopimelic acid as the diagnostic diamino acid. The major cellular
      fatty acids were anteiso-C(15 : 0), iso-C(15 : 0), anteiso-C(17 : 0) and iso-C(16
      : 0). The G+C content of its genomic DNA was 38.2 mol%. The affiliation of strain
      S1LM8(T) with the species of the genus Alkalibacillus was determined by 16S rRNA
      gene sequence comparison. The most closely related species were Alkalibacillus
      halophilus YIM 012(T) with 99.8% similarity, Alkalibacillus salilacus BH163(T)
      with 99.8% similarity and Alkalibacillus flavidus ISL-17(T) with 98.1% similarity
      between their 16S rRNA gene sequences. However, DNA-DNA relatedness between the
      novel isolate and the related species of the genus Alkalibacillus was less than
      34%. Based on the phylogenetic, phenotypic and chemotaxonomic features, a novel
      species, Alkalibacillus almallahensis sp. nov. is proposed. The type strain is
      S1LM8(T) ( = CECT 8373(T) = DSM 27545(T)).

PMID- 24670896
TI  - Defluviimonas indica sp. nov., a marine bacterium isolated from a deep-sea
      hydrothermal vent environment.
AB  - A Gram-stain-negative, strictly aerobic, chemoheterotrophic marine bacterium,
      designated 20V17(T), was isolated from a deep-sea hydrothermal vent chimney
      collected from the South-west Indian Ridge. Cells of strain 20V17(T) were motile,
      short rods, 1.2-1.8 um in length and 0.5-0.7 um in width. Growth was observed at
      between 20 and 37  degrees C (optimum 25  degrees C-28  degrees C), pH 5.0 and
      8.0 (optimum pH 7.0) and 0.5 and 8% (w/v) NaCl (optimum 1.5-2.0% NaCl). The major
      fatty acids were C(18 : 1)omega7c (74.4%), C(19 : 0) cyclo omega8c (11%), C(18 :
      0) (5.1%) and C(18 : 0) 3-OH (2.8%), and the polar lipid profile comprised
      diphosphatidylglycerol, phosphatidylethanolamine, an unidentified glycolipid and
      four unidentified phospholipids. Ubiquinone 10 was the major quinone. The G+C
      content of genomic DNA was 66.3 mol%. Phylogenetic analyses based on 16S rRNA
      gene sequences showed that strain 20V17(T) belonged to the genus Defluviimonas
      and shared 96.5 and 96.1% sequence similarity with Defluviimonas denitrificans D9
      3(T) and Defluviimonas aestuarii BS14(T), respectively. On the basis of the
      taxonomic data obtained in this study, strain 20V17(T) represents a novel species
      of the genus Defluviimonas, for which the name Defluviimonas indica sp. nov. is
      proposed. The type strain is 20V17(T) (CGMCC 1.10859(T) = JCM 17871(T) = MCCC
      1A01802(T)).

PMID- 24670897
TI  - Methanohalophilus levihalophilus sp. nov., a slightly halophilic, methylotrophic
      methanogen isolated from natural gas-bearing deep aquifers, and emended
      description of the genus Methanohalophilus.
AB  - A mesophilic, slightly halophilic, obligately methylotrophic, methanogenic
      archaeon, designated strain GTA13(T), was isolated from natural gas-bearing
      confined aquifers in the Minami-Kanto gas field, Japan. The cells were non
      motile, slightly irregular cocci, 0.7-1.0 um in diameter and occurred singly, in
      pairs or as small aggregates. The cells grew with tri- or dimethylamine but not
      with H2/CO2, formate, acetate, methanol or dimethyl sulphide. Vitamins, sodium
      and magnesium were required for growth. Optimal growth occurred at pH 7.0-7.5, 35
      degrees C, 0.35-0.40 M NaCl and 15-50 mM MgCl2. The NaCl range for growth was
      0.2-1.3 M. The DNA G+C content was 43.7 mol%. Strain GTA13(T) showed highest
      levels of 16S rRNA gene sequence similarity with Methanohalophilus portucalensis
      FDF-1(T) (96.4% sequence similarity) and Methanohalophilus halophilus DSM 3094(T)
      (96.0%). On the basis of physiological and phylogenetic features, strain GTA13(T)
      is considered to represent a novel species of the genus Methanohalophilus, for
      which the name Methanohalophilus levihalophilus sp. nov. is proposed. The type
      strain is GTA13(T) ( = NBRC 110099(T) = DSM 28452(T)). An emended description of
      the genus Methanohalophilus is also proposed.

PMID- 24670898
TI  - Nocardioides opuntiae sp. nov., isolated from soil of a cactus.
AB  - A novel high G+C actinobacterium, designated strain OS1-21(T), was isolated from
      the rhizosphere soil of a cactus (Opuntia fiscus-indica var. sanboten) and the
      taxonomic status was investigated using a polyphasic approach. Cells of strain
      OS1-21(T) were aerobic, Gram-stain-positive, non-endospore-forming, non-motile
      rods; colonies of the cells were circular, translucent, smooth and moderate
      yellow in colour. LL-Diaminopimelic acid was the diagnostic diamino acid in cell
      wall peptidoglycan. The predominant menaquinone was MK-8(H4). The major fatty
      acids were iso-C(16 : 0), iso-C(16 : 0) 2-OH, 10-methyl C(17 : 0), 10-methyl C(18
      : 0) and C(17 : 1)cis9. The polar lipids contained diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol and two unknown phospholipids. The DNA
      G+C content was 73.7 mol%. Based on 16S rRNA gene sequence analysis, the closest
      phylogenetic neighbours were Nocardioides panacihumi Gsoil 616(T) (98.7% sequence
      similarity) and Nocardioides terrae VA15(T) (97.8%), followed by Nocardioides
      marinus CL-DD14(T) (97.1%). DNA-DNA relatedness values of strain OS1-21(T) with
      the type strains of the closest phylogenetic neighbours were low (<16.0%).
      Combined data of polyphasic taxonomic analyses revealed that the organism could
      be assigned to a novel species of the genus Nocardioides, for which the name
      Nocardioides opuntiae sp. nov. is proposed. The type strain is OS1-21(T) ( = KCTC
      19804(T) = NBRC 107915(T)).

PMID- 24670899
TI  - Healthcare information on YouTube: A systematic review.
AB  - This article reviews the peer-reviewed literature addressing the healthcare
      information available on YouTube. Inclusion and exclusion criteria were
      determined, and the online databases PubMed and Web of Knowledge were searched
      using the search phrases: (1) YouTube* AND Health* and (2) YouTube* AND
      Healthcare*. In all, 18 articles were reviewed, with the results suggesting that
      (1) YouTube is increasingly being used as a platform for disseminating health
      information; (2) content and frame analysis were the primary techniques employed
      by researchers to analyze the characteristics of this information; (3) YouTube
      contains misleading information, primarily anecdotal, that contradicts the
      reference standards and the probability of a lay user finding such content is
      relatively high; (4) the retrieval of relevant videos is dependent on the search
      term used; and (5) videos from government organizations and professional
      associations contained trustworthy and high-quality information. YouTube is used
      as a medium for promoting unscientific therapies and drugs that are yet to be
      approved by the appropriate agencies and has the potential to change the beliefs
      of patients concerning controversial topics such as vaccinations. This review
      recognizes the need to design interventions to enable consumers to critically
      assimilate the information posted on YouTube with more authoritative information
      sources to make effective healthcare decisions. 

PMID- 24670900
TI  - AspC-mediated aspartate metabolism coordinates the Escherichia coli cell cycle.
AB  - BACKGROUND: The fast-growing bacterial cell cycle consists of at least two
      independent cycles of chromosome replication and cell division. To ensure proper
      cell cycles and viability, chromosome replication and cell division must be
      coordinated. It has been suggested that metabolism could affect the Escherichia
      coli cell cycle, but the idea is still lacking solid evidences.
      METHODOLOGY/PRINCIPLE FINDINGS: We found that absence of AspC, an
      aminotransferase that catalyzes synthesis of aspartate, led to generation of
      small cells with less origins and slow growth. In contrast, excess AspC was found
      to exert the opposite effect. Further analysis showed that AspC-mediated
      aspartate metabolism had a specific effect in the cell cycle, as only extra
      aspartate of the 20 amino acids triggered production of bigger cells with more
      origins per cell and faster growth. The amount of DnaA protein per cell was found
      to be changed in response to the availability of AspC. Depletion of (p)ppGpp by
      DeltarelADeltaspoT led to a slight delay in initiation of replication, but did
      not change the replication pattern found in the DeltaaspC mutant.
      CONCLUSION/SIGNIFICANCES: The results suggest that AspC-mediated metabolism of
      aspartate coordinates the E. coli cell cycle through altering the amount of the
      initiator protein DnaA per cell and the division signal UDP-glucose. Furthermore,
      AspC sequence conservation suggests similar functions in other organisms.

PMID- 24670901
TI  - A comparison of winter short-term and annual average radon measurements in
      basements of a radon-prone region and evaluation of further radon testing
      indicators.
AB  - The primary objective of this study was to investigate the temporal variability
      between basement winter short-term (7 to 10 d) and basement annual radon
      measurements. Other objectives were to test the short-term measurement's
      diagnostic performance at two reference levels and to evaluate its ability to
      predict annual average basement radon concentrations. Electret ion chamber (short
      term) and alpha track (annual) radon measurements were obtained by trained
      personnel in Iowa residences. Overall, the geometric mean of the short-term radon
      concentrations (199 Bq m) was slightly greater than the geometric mean of the
      annual radon concentrations (181 Bq m). Short-term tests correctly predicted
      annual radon concentrations to be above the 148 Bq m action level 88% of the time
      and above a 74 Bq m level 98% of the time. The short-term and annual radon
      concentrations were strongly correlated (r = 0.87, p < 0.0001). The foundation
      wall material of the basement was the only significant factor to have an impact
      on the absolute difference between the short-term and annual measurements. The
      findings from this study provide evidence of a substantially lower likelihood of
      obtaining a false negative result from a single short-term test in a region with
      high indoor radon potential when the reference level is lowered to 74 Bq m. 

PMID- 24670902
TI  - Gross alpha and beta activity analyses in urine-a routine laboratory method for
      internal human radioactivity detection.
AB  - The aim of this work was to develop a method to provide rapid results for humans
      with internal radioactive contamination. The authors hypothesized that valuable
      information could be obtained from gas proportional counter techniques by
      screening urine samples from potentially exposed individuals rapidly. Recommended
      gross alpha and beta activity screening methods generally employ gas proportional
      counting techniques. Based on International Standards Organization (ISO) methods,
      improvements were made in the evaporation process to develop a method to provide
      rapid results, adequate sensitivity, and minimum sample preparation and operator
      intervention for humans with internal radioactive contamination. The method
      described by an American National Standards Institute publication was used to
      calibrate the gas proportional counter, and urine samples from patients with or
      without radionuclide treatment were measured to validate the method. By improving
      the evaporation process, the time required to perform the assay was reduced
      dramatically. Compared with the reference data, the results of the validation
      samples were very satisfactory with respect to gross-alpha and gross-beta
      activities. The gas flow proportional counting method described here has the
      potential for radioactivity monitoring in the body. This method was easy,
      efficient, and fast, and its application is of great utility in determining
      whether a sample should be analyzed by a more complicated method, for example
      radiochemical and/or gamma-spectroscopy. In the future, it may be used commonly
      in medical examination and nuclear emergency treatment.Health Phys. 106(5):000
      000; 2014. 

PMID- 24670903
TI  - Accuracy of effective dose estimation in personal dosimetry: a comparison between
      single-badge and double-badge methods and the MOSFET method.
AB  - The purpose of this study was three-fold: (1) to measure the transmission
      properties of various lead shielding materials, (2) to benchmark the accuracy of
      commercial film badge readings, and (3) to compare the accuracy of effective dose
      (ED) conversion factors (CF) of the U.S. Nuclear Regulatory Commission methods to
      the MOSFET method. The transmission properties of lead aprons and the accuracy of
      film badges were studied using an ion chamber and monitor. ED was determined
      using an adult male anthropomorphic phantom that was loaded with 20 diagnostic
      MOSFET detectors and scanned with a whole body CT protocol at 80, 100, and 120
      kVp. One commercial film badge was placed at the collar and one at the waist.
      Individual organ doses and waist badge readings were corrected for lead apron
      attenuation. ED was computed using ICRP 103 tissue weighting factors, and ED CFs
      were calculated by taking the ratio of ED and badge reading. The measured single
      badge CFs were 0.01 (+/-14.9%), 0.02 (+/-9.49%), and 0.04 (+/-15.7%) for 80, 100,
      and 120 kVp, respectively. Current regulatory ED CF for the single badge method
      is 0.3; for the double-badge system, they are 0.04 (collar) and 1.5 (under lead
      apron at the waist). The double-badge system provides a better coefficient for
      the collar at 0.04; however, exposure readings under the apron are usually
      negligible to zero. Based on these findings, the authors recommend the use of ED
      CF of 0.01 for the single badge system from 80 kVp (effective energy 50.4 keV)
      data. 

PMID- 24670904
TI  - Time variation and strength distribution of air dose rate in Fukushima.
AB  - The author investigated functions that describe the air dose rate data in
      Fukushima, as such functions provide the time dependence of decay in the
      environment and ratios of high dose rate areas. Data were published by the
      Fukushima Prefectural and Koriyama City governments. Time variation data were
      fitted with a superposition of exponential functions, whereas air dose rate
      relative frequency data were fitted with several functions (Gauss, gamma, q
      Gauss, lognormal, and q-distribution). It was found that time variation data
      could be fitted well with a superposition of exponential functions and that the
      effective half-life of the radionuclide was markedly shorter than its physical
      half-life. Relative frequency data could be well fitted with a q-distribution.
      The strength distribution behaves like a power function for high air dose rate
      values (with an exponent <-4, where the exponent determines the behavior of the
      distribution for high air dose rate values). These findings are useful in
      estimating radiation exposure and high dose rate area ratios and are likely to be
      beneficial in protecting humans from radiation exposure. 

PMID- 24670905
TI  - Imaging plant leaves to determine changes in radioactive contamination status in
      Fukushima, Japan.
AB  - The chemical composition of plant leaves often reflects environmental
      contamination. The authors analyzed images of plant leaves to investigate the
      regional radioactivity ecology resulting from the 2011 accident at the Fukushima
      No. 1 nuclear power plant, Japan. The present study is not an evaluation of the
      macro radiation dose per weight, which has been performed previously, but rather
      an image analysis of the radioactive dose per leaf, allowing the capture of
      various gradual changes in radioactive contamination as a function of elapsed
      time. In addition, the leaf analysis method has potential applications in the
      decontamination of food plants or other materials. 

PMID- 24670906
TI  - A dose-reconstruction study of the 1997 Sarov criticality accident using animated
      dosimetry techniques.
AB  - Most computational human phantoms are static, representing a standing individual.
      There are, however, cases when these phantoms fail to represent accurately the
      detailed effects on dose that result from considering varying human posture and
      even whole sequences of motion. In this study, the feasibility of a dynamic and
      deformable phantom is demonstrated with the development of the Computational
      Human for Animated Dosimetry (CHAD) phantom. Based on modifications to the limb
      structure of the previously developed RPI Adult Male, CHAD's posture is
      adjustable using an optical motion capture system that records real-life human
      movement. To demonstrate its ability to produce dose results that reflect the
      changes brought about by posture-deformation, CHAD is employed to perform a dose
      reconstruction analysis of the 1997 Sarov criticality accident, and a simulated
      total body dose of 13.3 Gy is observed, with the total body dose rate dropping
      from 1.4 Gy s to 0.25 Gy s over the first 4 s of retreat time. Additionally, dose
      measurements are calculated for individual organs and body regions, including a
      36.8-Gy dose to the breast tissue, a 3.8-Gy dose to the bladder, and a 31.1-Gy
      dose to the thyroid, as well as the changes in dose rates for the individual
      organs over the course of the accident sequence. Comparison of results obtained
      using CHAD in an animated dosimetry simulation with reported information on dose
      and the medical outcome of the case shows that the consideration of posture and
      movement in dosimetry simulation allows for more detailed and precise analysis of
      dosimetry information, consideration of the evolution of the dose profile over
      time in the course of a given scenario, and a better understanding of the
      physiological impacts of radiation exposure for a given set of circumstances. 

PMID- 24670907
TI  - A proposed simple model for estimating occupational radiation dose to staff from
      veterinary 18F-FDG pet procedures.
AB  - Several studies have been conducted concerning the radiation dose to hospital
      personnel from positron emission tomography (PET) radiopharmaceuticals, but to
      date only one parallel study has been conducted for veterinary staff. Veterinary
      patients present challenges not encountered with human patients, as they require
      anesthesia and therefore more intensive monitoring than human patients. This
      paper presents a simple model for estimating the effective radiation dose to
      veterinary staff using occupational dose data from PET studies at Colorado State
      University's (CSU) James L. Voss Veterinary Teaching Hospital. The model consists
      of three point sources within a soft tissue cylinder, and sample calculations are
      provided for estimating dose to nuclear medicine technologists and an anesthesia
      technologist based on four different sized dogs. The estimated doses are within
      the range of actual occupational doses published previously. There are different
      protocols for the sequence of events in veterinary PET, specifically the order of
      anesthesia induction and radiopharmaceutical injection. When F-FDG injection is
      performed prior to anesthesia induction, the estimated dose is between 1.5 and
      3.6 times higher than the doses received if injection is done after anesthesia
      induction, although expected doses for both protocols are below occupational dose
      limits based on a case load of 100 veterinary patients per year. The model is
      based on the techniques used at CSU, but it can be modified for different
      hospitals as well as differently sized animals. 

PMID- 24670908
TI  - Efficacy of Prussian blue on 137Cs decorporation therapy.
AB  - Prussian blue (PB) is an efficient drug for enhancing cesium elimination from the
      body. Literature data on the efficacy of PB treatment in dosages that vary from 1
      10 g d was reviewed. Cesium biokinetics was simulated using a detailed systemic
      biokinetic model. The same model was used to simulate the maximum action of PB by
      interrupting the enterohepatic circulation. Model results reproduced reasonably
      well the literature data on the efficacy of PB administered to humans after
      incidental cesium intakes, as well as results from animal experiments. Maximum
      efficiency of the reduction of the long-term half-time is obtained with the
      administration of 3 g d PB to the adult. Maximum efficiency of reducing the Cs
      body burdens is obtained when PB is administered on the first day after the
      intake, due to the increase of the short-term elimination of cesium. The model
      predicts that reduction of the long-term half-life is not affected by the time
      after intake that PB is administered, as long as it is given within the interval
      from 1 h to 1 y after the intake. 

PMID- 24670909
TI  - On the air-filled effective porosity parameter of Rogers and Nielson's (1991)
      bulk radon diffusion coefficient in unsaturated soils.
AB  - The radon exhalation rate at the earth's surface from soil or rock with radium as
      its source is the main mechanism behind the radon activity concentrations
      observed in both indoor and outdoor environments. During the last two decades,
      many subsurface radon transport models have used Rogers and Nielson's formula for
      modeling the unsaturated soil bulk radon diffusion coefficient. This formula uses
      an "air-filled effective porosity" to account for radon adsorption and radon
      dissolution in the groundwater. This formula is reviewed here, and its hypotheses
      are examined for accuracy in dealing with subsurface radon transport problems.
      The author shows its limitations by comparing one dimensional steady-state
      analytical solutions of the two-phase (air/water) transport equation (Fick's law)
      with Rogers and Nielson's formula. For radon diffusion-dominated transport, the
      calculated Rogers and Nielson's radon exhalation rate is shown to be unrealistic
      as it is independent of the values of the radon adsorption and groundwater
      dissolution coefficients. For convective and diffusive transport, radon
      exhalation rates calculated using Fick's law and this formula agree only for high
      values of gas-phase velocity and groundwater saturation. However, these
      conditions are not usually met in most shallow subsurface environments where
      radon migration takes place under low gas phase velocities and low water
      saturation. 

PMID- 24670910
TI  - Differences in lung cancer mortality trends from 1986-2012 by radon risk areas in
      British Columbia, Canada.
AB  - Residential exposure to radon gas is associated with increased risk of lung
      cancer, especially in smokers. Most evidence about the health effects of radon
      has been derived from meta-analyses on global epidemiologic studies, but
      administrative data can help public health authorities to explore the local
      impacts. Eighty health units in British Columbia (BC), Canada, were classified as
      having low, moderate, or high radon risk using more than 3,800 residential
      measurements. Vital statistics records were used to identify deaths due to lung
      cancer and to all natural causes. The annual ratio of lung cancer mortality to
      all natural mortality was plotted for the 1986-2012 study period for each radon
      classification. Visualizations were stratified by gender and by smoking
      prevalence. The overall ratio increased throughout the study period in high radon
      areas and remained stable in low and moderate radon areas. The increase was most
      pronounced for females, especially when plots were stratified by smoking
      prevalence. These limited but interesting findings confirm that radon is one risk
      factor for lung cancer mortality in BC and that its effects differ across gender
      and smoking strata. The results would be strengthened by replication, and more
      rigorous methods are required to assess other contributing factors. 

PMID- 24670911
TI  - Shielding design for multiple-energy linear accelerators.
AB  - The introduction of medical linear accelerators (linacs) capable of producing
      three different x-ray energies has complicated the process of designing shielding
      for these units. The conventional approach for the previous generation of dual
      energy linacs relied on the addition of some amount of supplementary shielding to
      that calculated for the higher-energy beam, where the amount of that supplement
      followed the historical "two-source" rule, also known as the "add one HVL rule,"
      a practice derived from other two-source shielding considerations. The author
      describes an iterative approach that calculates shielding requirements accurately
      for any number of multiple beam energies assuming the workload at each energy can
      be specified at the outset. This method is particularly useful when considering
      the requirements for possible modifications to an existing vault when new
      equipment is to be installed as a replacement for a previous unit. 

PMID- 24670915
TI  - Porous-structured Cu2O/TiO2 nanojunction material toward efficient CO2
      photoreduction.
AB  - Porous-structured Cu2O/TiO2 nanojunction material is successfully fabricated by a
      facile method via loading Cu2O nanoparticles on the network of a porous TiO2
      substrate. The developed Cu2O/TiO2 nanojunction material has a size of several
      nanometers, in which the p-type Cu2O and n-type TiO2 nanoparticles are closely
      contacted with each other. The well designed nanojunction structure is beneficial
      for the charge separation in the photocatalytic reaction. Meanwhile, the porous
      structure of the Cu2O/TiO2 nanojunction can facilitate the CO2 adsorption and
      offer more reaction active sites. Most importantly, the gas-phase CO2
      photoreduction tests reveal that our developed porous-structured Cu2O/TiO2
      nanojunction material exhibits marked photocatalytic activity in the CH4
      evolution, about 12, 9, and 7.5 times higher than the pure TiO2, Pt-TiO2, and
      commercial Degussa P25 TiO2 powders, respectively. The greatly enhanced activity
      can be attributed to the well designed nanojunction structure combined with the
      porous structure, which can simultaneously enhance the charge separation
      efficiency and facilitate the CO2 adsorption. 

PMID- 24670916
TI  - Clinical networks influencing policy and practice: the establishment of advanced
      practice pharmacist roles for specialist palliative care services in South
      Australia.
AB  - OBJECTIVES: To operationalise the concept of 'advanced practice roles' in
      pharmacy within the new integrated regionalised palliative care service model
      outlined in the Palliative Care Services Plan 2009-2016, SA Health. METHODS: A
      working group was established under the auspices of the Palliative Care Clinical
      Network to progress the development of advanced practice pharmacist roles for
      regionalised palliative care services. A pharmacy stakeholder forum was conducted
      in December 2010 to provide further guidance on the advanced practice pharmacist
      roles in the following domains: education; network links and partnerships;
      quality and safety; and research. RESULTS: Advanced practice pharmacist positions
      were created for each of the three regionalised palliative care services in South
      Australia (SA). Funding was obtained for a Statewide Palliative Care Pharmacy
      Network project, to build a sustainable community-based palliative care pharmacy
      network. Advanced practice pharmacists commenced in the regionalised palliative
      care services of SA on 4 October 2011. CONCLUSIONS: The Statewide Palliative Care
      Clinical Network and the SA Palliative Care Plan provided a policy framework that
      supported involvement and advocacy in the planning of the advanced practice
      pharmacist roles. Collaboration between leaders in workforce reform, service
      planners, specialist palliative care providers and the pharmacy sector was a key
      enabler for developing the advanced practice pharmacist positions for
      regionalised palliative care services. What is known about the topic? The
      advanced practice palliative care pharmacist role reflects a new direction for
      the discipline of pharmacy and has been embraced at a time when a nationally
      endorsed Advanced Pharmacy Practice Framework has been published, while
      recognising that registration for pharmacists in Australia currently does not
      have specific endorsement for advanced practice. What does this paper add? This
      paper outlines the value of collaboration across settings and sectors. There is
      an opportunity for these roles to align with the new nationally endorsed
      framework for advanced practice in pharmacy. What are the implications for
      practitioners? These new positions strengthen the links between the hospital and
      community pharmacy sectors to enhance a quality use of medicines approach with
      improved access to end-of-life medicines for home-based palliative care clients,
      which actively facilitates a home death for those who choose it.

PMID- 24670918
TI  - Repair of ionizing radiation-induced DNA damage and risk of second cancer in
      childhood cancer survivors.
AB  - The study's purpose was to assess whether individuals who developed a second
      malignant neoplasm (SMN) after treatment for a first malignant neoplasm (FMN) had
      a lower ability to repair DNA double-strand breaks (DSBs) using a bioassay with
      gammaH2AX intensity as a surrogate endpoint. In a case-control study nested in a
      cohort of childhood cancer survivors, lymphoblastoid cell lines (LCLs) were
      established from blood samples collected from 94 cases (SMN) and 94 matched
      controls (FMN). LCLs were irradiated with ionizing radiation (2 and 5 Gy) and
      gammaH2AX intensities measured 1, 3, 5 and 24h post-irradiation. Differences in
      mean gammaH2AX intensity between cases and controls were compared using Kruskal
      Wallis tests. Generalized linear models for repeated measures and conditional
      logistic regressions for SMN risk estimates were performed. The mean baseline
      gammaH2AX intensity measured without irradiation was 9.1 [95% confidence interval
      (95% CI): 8.5-9.7] in the LCLs from cases and 6.4 (95% CI: 6.0-6.8) from controls
      (P < 0.001). Markedly higher gammaH2AX intensity, particularly at 1 h post
      irradiation, was also found in the LCLs from the cases compared with the controls
      for all FMNs and for different types of FMN. Chemotherapy and radiation doses
      received by bone marrow and thymus for FMN treatment showed a non-significant
      effect on gammaH2AX intensity. This case-control study shows that higher baseline
      and post-irradiation levels of DNA DSBs, as measured by gammaH2AX intensity, are
      associated with the risk of SMN in childhood cancer survivors. Further
      investigations in a prospective setting are warranted to confirm this
      association. 

PMID- 24670917
TI  - Genetic variants in interleukin genes are associated with breast cancer risk and
      survival in a genetically admixed population: the Breast Cancer Health
      Disparities Study.
AB  - Interleukins (ILs) are key regulators of immune response. Genetic variation in IL
      genes may influence breast cancer risk and mortality given their role in cell
      growth, angiogenesis and regulation of inflammatory process. We examined 16 IL
      genes with breast cancer risk and mortality in an admixed population of
      Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic
      white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product
      (ARTP) analysis was conducted to determine gene significance and lasso (least
      absolute shrinkage and selection operator) was used to identify potential gene by
      gene and gene by lifestyle interactions. The pathway was statistically
      significant for breast cancer risk overall (P ARTP = 0.0006), for women with low
      NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for
      estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and
      ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated
      with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four
      genes were associated with breast cancer risk among women with low NA ancestry
      (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among
      women with high NA ancestry (IL2 and IL2RA) and four genes were associated with
      premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and
      IL17A were associated with breast cancer-specific mortality. We confirmed
      associations with several functional polymorphisms previously associated with
      breast cancer risk and provide support that their combined effect influences the
      carcinogenic process.

PMID- 24670919
TI  - Resonant metasurfaces at oblique incidence: interplay of order and disorder.
AB  - Understanding the impact of order and disorder is of fundamental importance to
      perceive and to appreciate the functionality of modern photonic metasurfaces.
      Metasurfaces with disordered and amorphous inner arrangements promise to mitigate
      problems that arise for their counterparts with strictly periodic lattices of
      elementary unit cells such as, e.g., spatial dispersion, and allows the use of
      fabrication techniques that are suitable for large scale and cheap fabrication of
      metasurfaces. In this study, we analytically, numerically and experimentally
      investigate metasurfaces with different lattice arrangements and uncover the
      influence of lattice disorder on their electromagnetic properties. The considered
      metasurfaces are composed of metal-dielectric-metal elements that sustain both
      electric and magnetic resonances. Emphasis is placed on understanding the effect
      of the transition of the lattice symmetry from a periodic to an amorphous state
      and on studying oblique illumination. For this scenario, we develop a powerful
      analytical model that yields, for the first time, an adequate description of the
      scattering properties of amorphous metasurfaces, paving the way for their
      integration into future applications. 

PMID- 24670921
TI  - Maternal microchimerism in biliary atresia: are maternal cells effector cells,
      targets, or just bystanders?
AB  - The etiology of biliary atresia (BA) is unknown; however, the liver histology is
      similar to that observed in immune-mediated hepatic disorders. Liver fibrosis in
      BA progresses even after bile drainage has been achieved by the Kasai operation.
      Maternal microchimerism has been purported to play a part in the pathogenesis of
      BA as well as certain autoimmune diseases. However, the role of maternal cells
      has not yet been determined in BA. Specifically, it is unknown whether these
      maternal cells function as maternal effector T lymphocytes, or targets or
      bystanders. We currently hypothesize that the first hit is due to GvHD
      interaction by engrafted maternal effector T lymphocytes. Furthermore, we suggest
      that the secondary effects that are manifested by progressive cirrhosis are
      caused either by maternal chimeric effector T lymphocytes (e.g., GvHD
      interaction) or targets (e.g., HvGD interaction). Based on our hypothesis, mixed
      lymphocyte reactions between patients and their mothers might shed light on the
      etiopathogenesis and prognostic indicators. 

PMID- 24670922
TI  - A novel role of sympathetic activity in regulating mitral valve prolapse.
AB  - BACKGROUND: Increased sympathetic activity, commonly reported in mitral valve
      prolapse, indicates that the sympathetic nervous system might play an important
      role in regulating mitral interstitial cells. Hence, the aim of this study is to
      determine the level and pattern of adrenergic receptors expressed in human mitral
      valve leaflets and to investigate the effect of norepinephrine on physiologic
      behaviors of mitral interstitial cells. METHODS AND RESULTS: Immunohistochemistry
      displayed significantly increased expressions of beta1, beta2, and alpha1
      adrenergic receptors in mitral valve prolapse. Norepinephrine was found to
      activate the phenotype of interstitial cells with increased alpha-SMA expression
      (2.26 fold). In synthesis, norepinephrine downregulated levels of mRNA for type I
      to type III collagen in ratio, but increased the elastin gene transcription and
      glycosaminoglycan levels in valve interstitial cells greatly. In view of the
      extracellular matrix remodel, sympathetic effects presented catabolic metabolism
      displaying significantly increased expressions of total, secretory and active MMP
      2 protein (matrix metalloproteinase-2), as well as MMP-9 protein. Diminished MMP
      inhibitor expression, TIMP2, also could reflect this effect in the norepinephrine
      medium. CONCLUSIONS: A novel role for the sympathetic effect in influencing
      physiologic behaviors in mitral interstitial cells was identified. It is
      indicated that sympathetic activity could promote myxomatous degeneration in
      mitral valve prolapse, propagating the disease severity, which might identify
      potential therapeutic targets.

PMID- 24670920
TI  - Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.
AB  - Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular
      alterations underlying the pathogenesis of these tumours have not been
      systematically studied so far. Here we perform gene copy number analysis (n=54),
      genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids
      and observe frequent mutations in chromatin-remodelling genes. Covalent histone
      modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the
      cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In
      contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours,
      TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are
      not early progenitor lesions of the highly aggressive lung neuroendocrine tumours
      but arise through independent cellular mechanisms. These data also suggest that
      inactivation of chromatin-remodelling genes is sufficient to drive transformation
      in pulmonary carcinoids. 

PMID- 24670923
TI  - Circadian variation of Rho-kinase activity in circulating leukocytes of patients
      with vasospastic angina.
AB  - BACKGROUND: Vasospastic angina (VSA) is known to exhibit circadian variation with
      an early morning peak. We examined whether Rho-kinase activity in circulating
      leukocytes, which is a useful biomarker for disease activity assessment of VSA,
      exhibits circadian variation in patients with VSA. METHODS AND RESULTS: In
      consecutive 31 VSA patients (M/F 23/8, 57+/-13 [SD] years) and 18 non-VSA
      patients (M/F 8/10, 57+/-14 years), we measured Rho-kinase activity in
      circulating leukocytes at 6:00, 12:00 and 21:00. We also examined the
      relationship between the Rho-kinase activity and coronary vasomotor responses
      during provocation test. Rho-kinase activity was significantly higher in VSA
      patients than in non-VSA patients at 6:00 (1.17+/-0.17 vs. 0.92+/-0.22, P<0.001),
      and showed a significant circadian variation with a peak at 6:00 (1.00+/-0.15 at
      21:00, 1.17+/-0.17 at 6:00 and 1.12+/-0.22 at 12:00, P<0.001) in VSA patients,
      whereas no such variation was noted in non-VSA patients. Importantly, Rho-kinase
      activity at spasm provocation test was significantly correlated with basal
      coronary tone defined by vasodilating responses to intracoronary nitrate (r=0.40,
      P<0.05) and coronary vasoconstricting responses to acetylcholine (r=0.44, P<0.05)
      in VSA patients. Furthermore, their Rho-kinase activity at 6:00 was positively
      correlated with nocturnal parasympathetic activity as evaluated by heart rate
      variability in Holter monitoring (r=0.48, P<0.05). CONCLUSIONS: Rho-kinase
      activity exhibits distinct circadian variation associated with alterations in
      coronary vasomotor responses and autonomic activity in VSA patients.

PMID- 24670924
TI  - Aortic valve reconstruction with autologous glutaraldehyde-treated pericardium--a
      new paradigm for aortic valve surgery?

PMID- 24670925
TI  - Rate of atherosclerosis progression in ApoE-/- mice long after discontinuation of
      cola beverage drinking.
AB  - This study was conducted in order to evaluate the effect of cola beverages
      drinking on atherosclerosisand test the hypothesis whether cola beverages
      consumption at early life stages might affect the development and progression of
      atherosclerosis later in life. ApoE-/- C57BL/6J mice (8 week-old) were randomized
      in 3 groups (n = 20 each) according to free accessto water (W), sucrose sweetened
      carbonated cola drink(C) or aspartame-acesulfame K sweetened carbonated 'light'
      cola drink (L)for the next 8 weeks. Drinking treatment was ended by switching C
      and L groups to drinking water. Four mice per group and time were sequentially
      euthanized: before treatment (8 weeks-old), at the end of treatment (16 weeks
      old) and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old
      mice). Aortic roots and livers were harvested, processed for histology and serial
      cross-sections were stained. Aortic plaque area was analyzed and plaque/media
      ratio was calculated. Early consumption of cola drinks accelerated
      atherosclerotic plaque progression favoring the interaction between macrophages
      and myofibroblasts, without the participation of either T lymphocytes or
      proliferative activity. Plaque/media-ratio varied according to drink treatment
      (F2,54 = 3.433, p<0.04) and mice age (F4,54 = 5.009, p<0.03) and was higher in C
      and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks,
      p<0.01 at 24 weeks and 30 weeks). Natural evolution of atherosclerosis in ApoE-/-
      mice (W group) evidenced atherosclerosis acceleration in parallel with a rapid
      increase in liver inflammation around the 20 weeks of age. Cola drinking within
      the 8-16 weeks of age accelerated atherosclerosis progression in ApoE-/- mice
      favoring aortic plaque enlargement (inward remodeling) over media thinning all
      over the study time. Data suggest that cola drinking at early life stages may
      predispose to atherosclerosis progression later in life in ApoE-/- mice.

PMID- 24670926
TI  - Invasive cancer incidence - United States, 2010.
AB  - Cancer has many causes, some of which can, at least in part, be avoided through
      interventions known to reduce cancer risk. Healthy People 2020 objectives call
      for reducing colorectal cancer incidence to 38.6 per 100,000 persons, reducing
      late-stage breast cancer incidence to 41.0 per 100,000 women, and reducing
      cervical cancer incidence to 7.1 per 100,000 women. To assess progress toward
      reaching these Healthy People 2020 targets, CDC analyzed data from U.S. Cancer
      Statistics (USCS) for 2010. USCS includes incidence data from CDC's National
      Program of Cancer Registries and the National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) program and mortality data from the National
      Vital Statistics System. In 2010, a total of 1,456,496 invasive cancers were
      reported to cancer registries in the United States (excluding Arkansas and
      Minnesota), an annual incidence rate of 446 cases per 100,000 persons, compared
      with 459 in 2009. Cancer incidence rates were higher among men (503) than women
      (405), highest among blacks (455), and ranged by state from 380 to 511 per
      100,000 persons. Many factors, including tobacco use, obesity, insufficient
      physical activity, and human papilloma virus (HPV) infection, contribute to the
      risk for developing cancer, and differences in cancer incidence indicate
      differences in the prevalence of these risk factors. These differences can be
      reduced through policy approaches such as the Affordable Care Act, which could
      increase access for millions of persons to appropriate and timely cancer
      preventive services, including help with smoking cessation, cancer screening, and
      vaccination against HPV.

PMID- 24670927
TI  - CDC grand rounds: Creating a healthier future through prevention of child
      maltreatment.
AB  - Child maltreatment is abuse or neglect of a child by a parent or other caregiver
      that results in potential or actual harm or threats of harm to a child.
      Maltreatment encompasses both acts of commission (abuse) and omission (neglect).
      Child maltreatment is divided into four types: 1) physical abuse (e.g., hitting,
      kicking, shaking, or burning); 2) sexual abuse (e.g., rape or fondling); 3)
      psychological abuse (e.g., terrorizing or belittling); and 4) neglect, which
      involves the failure to meet a child's basic physical, emotional, or educational
      needs (e.g., not providing nutrition, shelter, or medical or mental health care)
      or the failure to supervise the child in a way that ensures safety (e.g., not
      taking reasonable steps to prevent injury). In 2012, a total of 1,593 children
      were reported to have died as a result of maltreatment in the United States. Also
      in 2012, state child protective service (CPS) agencies received an estimated 3.4
      million reports of alleged maltreatment, involving an estimated 6.3 million
      children. Following the CPS investigation or other response, nearly 700,000
      children were confirmed as having been maltreated. However, many cases are never
      reported to authorities; the actual scope of child maltreatment is greater. For
      example, data from a nationally representative survey in 2011 of children and
      adult caregivers (usually parents) suggest that 13.8% of children are maltreated
      each year and 25.6% experienced maltreatment at some point during childhood. 

PMID- 24670928
TI  - State medicaid coverage for tobacco cessation treatments and barriers to coverage
      - United States, 2008-2014.
AB  - Medicaid enrollees have a higher smoking prevalence than the general population
      (30.1% of adult Medicaid enrollees aged <65 years smoke, compared with 18.1% of
      U.S. adults of all ages), and smoking-related disease is a major contributor to
      increasing Medicaid costs. Evidence-based cessation treatments exist, including
      individual, group, and telephone counseling and seven Food and Drug
      Administration (FDA)-approved medications. A Healthy People 2020 objective (TU-8)
      calls for all state Medicaid programs to adopt comprehensive coverage of these
      treatments. However, most states do not provide such coverage. To monitor trends
      in state Medicaid cessation coverage, the American Lung Association collected
      data on coverage of all evidence-based cessation treatments except telephone
      counseling by state Medicaid programs (for a total of nine treatments), as well
      as data on barriers to accessing these treatments (such as charging copayments or
      limiting the number of covered quit attempts) from December 31, 2008, to January
      31, 2014. As of 2014, all 50 states and the District of Columbia cover some
      cessation treatments for at least some Medicaid enrollees, but only seven states
      cover all nine treatments for all enrollees. Common barriers in 2014 include
      duration limits (40 states for at least some populations or plans), annual limits
      (37 states), prior authorization requirements (36 states), and copayments (35
      states). Comparing 2008 with 2014, 33 states added treatments to coverage, and 22
      states removed treatments from coverage; 26 states removed barriers to accessing
      treatments, and 29 states added new barriers. The evidence from previous analyses
      suggests that states could reduce smoking-related morbidity and health-care costs
      among Medicaid enrollees by providing Medicaid coverage for all evidence-based
      cessation treatments, removing all barriers to accessing these treatments,
      promoting the coverage, and monitoring its use.

PMID- 24670929
TI  - Notes from the field: Heartland virus disease - United States, 2012-2013.
AB  - Heartland virus is a newly identified phlebovirus that was first isolated from
      two northwestern Missouri farmers hospitalized with fever, leukopenia, and
      thrombocytopenia in 2009. Based on the patients' clinical findings and their
      reported exposures, the virus was suspected to be transmitted by ticks. After
      this discovery, CDC worked with state and local partners to define the ecology
      and modes of transmission of Heartland virus, develop diagnostic assays, and
      identify additional cases to describe the epidemiology and clinical disease. From
      this work, it was learned that Heartland virus is found in the Lone Star tick
      (Amblyomma americanum). Six additional cases of Heartland virus disease were
      identified during 2012-2013; four of those patients were hospitalized, including
      one with comorbidities who died. 

PMID- 24670930
TI  - DIF-1 inhibits tumor growth in vivo reducing phosphorylation of GSK-3beta and
      expressions of cyclin D1 and TCF7L2 in cancer model mice.
AB  - We reported that differentiation-inducing factor-1 (DIF-1), synthesized by
      Dictyostelium discoideum, inhibited proliferation of various tumor cell lines in
      vitro by suppressing the Wnt/beta-catenin signaling pathway. However, it remained
      unexplored whether DIF-1 also inhibits tumor growth in vivo. In the present
      study, therefore, we examined in-vivo effects of DIF-1 using three cancer models:
      Mutyh-deficient mice with oxidative stress-induced intestinal tumors and nude
      mice xenografted with the human colon cancer cell line HCT-116 and cervical
      cancer cell line HeLa. In exploration for an appropriate route of administration,
      we found that orally administered DIF-1 was absorbed through the digestive tract
      to elevate its blood concentration to levels enough to suppress tumor cell
      proliferation. Repeated oral administration of DIF-1 markedly reduced the number
      and size of intestinal tumors that developed in Mutyh-deficient mice, reducing
      the phosphorylation level of GSK-3beta Ser(9) and the expression levels of early
      growth response-1 (Egr-1), transcription factor 7-like 2 (TCF7L2) and cyclin D1.
      DIF-1 also inhibited the growth of HCT-116- and HeLa-xenograft tumors together
      with decreasing phosphorylation level of GSK-3beta Ser(9), although it was not
      statistically significant in HeLa-xenograft tumors. DIF-1 also suppressed the
      expressions of Egr-1, TCF7L2 and cyclin D1 in HCT-116-xenograft tumors and those
      of beta-catenin, TCF7L2 and cyclin D1 in HeLa-xenograft tumors. This is the first
      report to show that DIF-1 inhibits tumor growth in vivo, consistent with its in
      vitro action, suggesting that this compound may have potential as a novel anti
      tumor agent. 

PMID- 24670931
TI  - Correlates among nocturnal agitation, sleep, and urinary incontinence in
      dementia.
AB  - Family caregivers of elders with dementia often face the challenging behaviors of
      nighttime agitation, sleep disturbances, and urinary incontinence. To date, no
      study has examined the interrelationships of these behaviors in community
      dwelling persons. This single group, descriptive study employs wireless body
      sensors to objectively collect data on nighttime agitation, sleep, and urinary
      incontinence in patients with dementia in their homes over a 5- to 7-day period.
      The aims are to (1) examine the feasibility and acceptability of the use of body
      sensors in community-dwelling persons with dementia; (2) describe patterns of
      nocturnal agitation, sleep continuity and duration, and nighttime urinary
      incontinence; and (3) examine the relationships among nocturnal agitation, sleep
      continuity and duration, and nighttime urinary incontinence. Data collection is
      in early stages and is still in progress. Challenges and advantages from
      preliminary data collection are reported. 

PMID- 24670933
TI  - In situ atomic force microscopy study of initial solid electrolyte interphase
      formation on silicon electrodes for Li-ion batteries.
AB  - Precise in situ atomic force microscopy (AFM) is used to monitor the formation of
      the solid electrolyte interphase (SEI) on Si electrodes. The stability of these
      passivation films on negative electrodes is critically important in rechargeable
      Li-ion batteries, and high capacity materials such as Si present substantial
      challenges because of the large volume changes that occur with Li insertion and
      removal. The results reported here show that the initial rapid SEI formation can
      be stabilized before significant Li insertion into the Si begins and that the
      rate at which this occurs varies significantly with the nature of the surface.
      The initial cycling conditions also have a substantial impact on the SEI that
      forms, with faster rates leading to a smoother, thinner SEI film. To
      quantitatively interpret the SEI measurements, irreversible expansion of the Si
      during the first cycle was also monitored in situ with specifically designed
      specimen configurations. On the basis of the experimental results, relatively
      simple models were also used to describe the initial formation and stabilization
      of the SEI and to describe the relationship between the SEI thickness and
      expected SEI degradation mechanisms. 

PMID- 24670932
TI  - Characterization of azoxymethane-induced colon tumor metastasis to lung in a
      mouse model relevant to human sporadic colorectal cancer and evaluation of grape
      seed extract efficacy.
AB  - The second leading cause of cancer-related deaths (both genders combined) in the
      United States is colorectal cancer (CRC). This emphasizes the need to develop
      both effective therapies for CRC patients and pre-clinical models mimicking human
      disease that carry translational potential in drug-development. Notably, at
      present there are no in situ models of CRC metastasis to lung. In our
      azoxymethane-induced colon tumorigenesis study in A/J mice assessing grape seed
      extract (GSE) efficacy, during necropsy we also found multiple lung nodules
      suggestive of colon tumor metastasis to lung that were significantly inhibited in
      GSE fed group. Both histopathological and molecular studies were performed to
      characterize and establish the origin of these lesions in lung. Histologically
      these nodules were determined as adenocarcinoma of mucin origin. Molecular
      analyses by immunohistochemistry (IHC) and RT-PCR revealed strong protein and
      transcript levels of colon specific markers CDX2 and CK20 in these lung nodules
      compared to uninvolved control lung tissue. Vis-a-vis, these nodules also showed
      minimally expressed lung specific biomarkers, specifically surfactant D and TTF
      1, in IHC analysis. Additionally, 0.25% GSE supplementation in diet (w/w)
      decreased the incidence of these lung nodules by 53% and their total number by
      66%. Together, the characterization of this unique in situ mouse model of CRC
      metastasis to lung provides translational opportunities in developing effective
      therapies to clinically manage and treat CRC at the advanced stage. Moreover, GSE
      efficacy in inhibiting CRC metastasis to lung in this model further supports its
      translational potential in controlling CRC growth, progression and metastasis in
      patients. 

PMID- 24670934
TI  - Factors associated with transfers from healthcare facilities among readmitted
      older adults with chronic illness.
AB  - OBJECTIVE: Because chronic illness accounts for a considerable proportion of
      Australian healthcare expenditure, there is a need to identify factors that may
      reduce hospital readmissions for patients with chronic illness. The aim of the
      present study was to examine a range of factors potentially associated with
      transfer from healthcare facilities among older adults readmitted to hospital
      within a large public health service in Melbourne, Australia. METHODS: Data on
      readmitted patients between June 2006 and June 2011 were extracted from hospital
      databases and medical records. Adopting a retrospective case-control study
      design, a sample of 51 patients transferred from private residences was matched
      by age and gender with 55 patients transferred from healthcare facilities
      (including nursing homes and acute care facilities). Univariate and multivariate
      logistic regression analyses were used to compare the two groups, and to
      determine associations between 46 variables and transfer from a healthcare
      facility. RESULTS: Univariate analysis indicated that patients readmitted from
      healthcare facilities were significantly more likely to experience relative
      socioeconomic advantage, disorientation on admission, dementia diagnosis,
      incontinence and poor skin integrity than those readmitted from a private
      residence. Three of these variables remained significantly associated with
      admission from healthcare facilities after multivariate analysis: relative
      socioeconomic advantage (odds ratio (OR) 11.30; 95% confidence interval (CI) 2.62
      48.77), incontinence (OR 7.18; 95% CI 1.19-43.30) and poor skin integrity (OR
      18.05; 95% CI 1.85-176.16). CONCLUSIONS: Older adults with chronic illness
      readmitted to hospital from healthcare facilities are significantly more likely
      to differ from those readmitted from private residences in terms of relative
      socioeconomic advantage, incontinence and skin integrity. The findings direct
      efforts towards addressing the apparent disparity in management of patients
      admitted from a facility as opposed to a private residence.

PMID- 24670935
TI  - Discovering pair-wise genetic interactions: an information theory-based approach.
AB  - Phenotypic variation, including that which underlies health and disease in
      humans, results in part from multiple interactions among both genetic variation
      and environmental factors. While diseases or phenotypes caused by single gene
      variants can be identified by established association methods and family-based
      approaches, complex phenotypic traits resulting from multi-gene interactions
      remain very difficult to characterize. Here we describe a new method based on
      information theory, and demonstrate how it improves on previous approaches to
      identifying genetic interactions, including both synthetic and modifier kinds of
      interactions. We apply our measure, called interaction distance, to previously
      analyzed data sets of yeast sporulation efficiency, lipid related mouse data and
      several human disease models to characterize the method. We show how the
      interaction distance can reveal novel gene interaction candidates in experimental
      and simulated data sets, and outperforms other measures in several circumstances.
      The method also allows us to optimize case/control sample composition for
      clinical studies. 

PMID- 24670936
TI  - Characteristics and outcomes for hospitalized patients with recurrent clinical
      deterioration and repeat medical emergency team activation*.
AB  - OBJECTIVE: To describe the occurrence of recurrent clinical deterioration and
      repeat medical emergency team activation and assess its effect on processes and
      outcomes of care. DESIGN: Retrospective cohort study. SETTING: Two community
      hospitals and two tertiary care hospitals, Alberta, Canada. PATIENTS: Consecutive
      hospitalized adult patients with sudden clinical deterioration and medical
      emergency team activation without admission to ICU. INTERVENTION: None.
      MEASUREMENT AND MAIN RESULTS: We compared ICU admission rates (admissions > 2 hr
      following index medical emergency team), hospital length of stay, and hospital
      mortality for a cohort of 3,200 patients with and without recurrent clinical
      deterioration following medical emergency team activation adjusting for patient,
      provider, and hospital characteristics.The cohort consisted of 3,200 patients.
      Ten percent of patients (n = 337) experienced recurrent clinical deterioration
      and repeat medical emergency team activation during their hospital stay. Patients
      more likely to experience recurrent clinical deterioration and repeat medical
      emergency team activation included those with chronic liver disease (odds ratio,
      1.75; 95% CI, 1.14-2.69) or who received airway suctioning (odds ratio, 1.66; 95%
      CI, 1.23-2.25), noninvasive mechanical ventilation (odds ratio, 1.67; 95% CI,
      0.94-2.94), or central IV catheter insertion (odds ratio, 1.81; 95% CI, 1.02
      3.21) during the index medical emergency team activation. Patients with recurrent
      clinical deterioration were more likely than patients without recurrent clinical
      deterioration to be subsequently admitted to ICU (43% vs 13%; odds ratio, 6.11;
      95% CI, 4.67-8.00; p < 0.01), to have longer lengths of hospital stay (median, 31
      d vs 13 d; p < 0.01), and to die during their hospital stay (34% vs 23%; odds
      ratio, 1.98; 95% CI, 1.47-2.67; p < 0.01). CONCLUSIONS: Recurrent clinical
      deterioration and repeat medical emergency team activation are common and
      associated with increased risk of subsequent ICU admission, increased length of
      hospital stay, and increased hospital mortality. It may be possible to identify
      patients at risk of recurrent clinical deterioration following medical emergency
      team activation and target interventions to improve patient care.

PMID- 24670937
TI  - Guideline bundles adherence and mortality in severe sepsis and septic shock.
AB  - OBJECTIVE: Surviving Sepsis Campaign bundles have been associated with reduced
      mortality in severe sepsis and septic shock patients. Case-mix adjusted mortality
      evaluations have not been performed to compare hospitals participating in sepsis
      bundle programs with those not participating. We aimed to achieve an individual
      bundle target adherence more than 80% and a relative mortality reduction of at
      least 15% (absolute mortality reduction 5.2%) at the end of 2012. DESIGN:
      Prospective multicenter cohort study in participating and nonparticipating
      centers. SETTING: Eighty-two ICUs in The Netherlands. PATIENTS: In total, 213,677
      adult ICU patients admitted to all ICUs among which 8,387 severe sepsis patients
      at 52 participating ICUs and 8,031 severe sepsis patients at 30 nonparticipating
      ICUs. INTERVENTIONS: A national program to screen patients for severe sepsis and
      septic shock and implement Surviving Sepsis Campaign bundles to complete within 6
      and 24 hours after ICU admission. MEASUREMENTS AND MAIN RESULTS: Bundle target
      adherence and case-mix adjusted in-hospital mortality were evaluated through odds
      ratios of time since program initiation by logistic generalized estimating
      equation analyses (July 2009 through January 2013). Outcomes were adjusted for
      age, gender, admission type, severity of illness, and sepsis diagnosis location.
      Participation duration was associated with improved bundle target adherence
      (adjusted odds ratio per month = 1.024 [1.016-1.031]) and decreased in-hospital
      mortality (adjusted odds ratio per month = 0.992 [0.986-0.997]) equivalent to
      5.8% adjusted absolute mortality reduction over 3.5 years. Mortality reduced in
      screened patients with other diagnoses (1.9% over 3.5 yr, adjusted odds ratio per
      month = 0.995 [0.9906-0.9996]) and did not change in nonscreened patients in
      participating ICUs, nor in patients with sepsis or other diagnoses in
      nonparticipating ICUs. CONCLUSIONS: Implementation of a national sepsis program
      resulted in improved adherence to sepsis bundles in severe sepsis and septic
      shock patients and was associated with reduced adjusted in-hospital mortality
      only in participating ICUs, suggesting direct impact of sepsis screening and
      bundle application on in-hospital mortality.

PMID- 24670938
TI  - Acute insulin resistance mediated by advanced glycation endproducts in severely
      burned rats.
AB  - OBJECTIVE: Hyperglycemia often occurs in severe burns; however, the underlying
      mechanisms and importance of managing postburn hyperglycemia are not well
      recognized. This study was designed to investigate the dynamic changes of
      postburn hyperglycemia and the underlying mechanisms and to evaluate whether
      early glycemic control is beneficial in severe burns. DESIGN: Prospective,
      randomized experimental study. SETTING: Animal research laboratory. SUBJECTS:
      Sprague-Dawley rats. INTERVENTIONS: Anesthetized rats were subjected to a full
      thickness burn injury comprising 40% of the total body surface area and were
      randomized to receive vehicle, insulin, and a soluble form of receptor for
      advanced glycation endproducts treatments. An in vitro study was performed on
      cultured H9C2 cells subjected to vehicle or carboxymethyllysine treatment.
      MEASUREMENTS AND MAIN RESULTS: We found that blood glucose change presented a
      distinct pattern with two occurrences of hyperglycemia at 0.5- and 3-hour
      postburn, respectively. Acute insulin resistance evidenced by impaired insulin
      signaling and glucose uptake occurred at 3-hour postburn, which was associated
      with the second hyperglycemia and positively correlated with mortality.
      Mechanistically, we found that serum carboxymethyllysine, a dominant species of
      advanced glycation endproducts, increased within 1-hour postburn, preceding the
      occurrence of insulin resistance. More importantly, treatment of animals with
      soluble form of receptor for advanced glycation endproducts, blockade of advanced
      glycation endproducts signaling, alleviated severe burn-induced insulin
      resistance. In addition, early hyperglycemic control with insulin not only
      reduced serum carboxymethyllysine but also blunted postburn insulin resistance
      and reduced mortality. CONCLUSIONS: These findings suggest that severe burn
      induced insulin resistance is partly at least mediated by serum advanced
      glycation endproducts and positively correlated with mortality. Early glycemic
      control with insulin or inhibition of advanced glycation endproducts with soluble
      form of receptor for advanced glycation endproducts ameliorates postburn insulin
      resistance.

PMID- 24670939
TI  - Effects of renal denervation on regional hemodynamics and kidney function in
      experimental hyperdynamic sepsis.
AB  - OBJECTIVE: To determine the influence of the renal sympathetic nerves on the
      pathogenesis of septic acute kidney injury. DESIGN: Interventional control study
      to determine the effects of renal denervation in ovine hyperdynamic sepsis.
      SETTING: Research Institute. SUBJECTS: Twenty-four adult Merino ewes.
      INTERVENTIONS: The effects of infusion of angiotensin II and norepinephrine and
      induction of hyperdynamic sepsis by administration of live Escherichia coli were
      examined in control sheep and in sheep at 2 weeks after bilateral renal
      denervation (n = 10/group). MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics
      and renal function were measured in conscious sheep instrumented with flow probes
      on the pulmonary and renal arteries. Angiotensin II, but not norepinephrine, had
      a greater pressor effect in denervated animals. Sepsis increased cardiac output
      by 60%, renal blood flow by 35%, and arterial lactate by approximately four-fold.
      The denervated compared with the control group had a greater degree of
      hypotension during sepsis (68 vs 81 mm Hg; p = 0.003) and a reduction in the
      early polyuric response (from 496 to 160 mL at 2-8 hr of sepsis; p < 0.001).
      Creatinine clearance decreased similarly in both groups. CONCLUSIONS: In
      experimental hyperdynamic sepsis, renal denervation was associated with greater
      hypotension and a loss of the initial diuresis, but no significant change in
      creatinine clearance. In sepsis, the renal nerves help support arterial pressure
      and determine the initial diuretic response, but septic acute kidney injury
      developed similarly in the innervated and denervated groups.

PMID- 24670940
TI  - Revisiting the Al/Al2O3 interface: coherent interfaces and misfit accommodation.
AB  - We study the coherent and semi-coherent Al/alpha-Al2O3 interfaces using molecular
      dynamics simulations with a mixed, metallic-ionic atomistic model. For the
      coherent interfaces, both Al-terminated and O-terminated nonstoichiometric
      interfaces have been studied and their relative stability has been established.
      To understand the misfit accommodation at the semi-coherent interface, a 1
      dimensional (1D) misfit dislocation model and a 2-dimensional (2D) dislocation
      network model have been studied. For the latter case, our analysis reveals an
      interface dislocation structure with a network of three sets of parallel
      dislocations, each with pure-edge character, giving rise to a pattern of coherent
      and stacking-fault-like regions at the interface. Structural relaxation at
      elevated temperatures leads to a further change of the dislocation pattern, which
      can be understood in terms of a competition between the stacking fault energy and
      the dislocation interaction energy at the interface. Our results are expected to
      serve as an input for the subsequent dislocation dynamics models to understand
      and predict the macroscopic mechanical behavior of Al/alpha-Al2O3 composite
      heterostructures. 

PMID- 24670941
TI  - Advice for fish consumption: challenging dilemmas.

PMID- 24670942
TI  - Introduction to nutrition education in training medical and other health care
      professionals.

PMID- 24670943
TI  - The New Nordic Diet is an effective tool in environmental protection: it reduces
      the associated socioeconomic cost of diets.
AB  - BACKGROUND: The New Nordic Diet (NND) was designed by gastronomic, nutritional,
      and environmental specialists to be a palatable, healthy, and sustainable diet
      containing 35% less meat than the Average Danish Diet (ADD); more whole-grain
      products, nuts, fruit, and vegetables; locally grown food in season; and >75%
      organic produce. The environmental impact of the 2 diets was compared based on 16
      impact categories, which were monetized to evaluate the overall socioeconomic
      effect of a shift from an ADD to an NND. OBJECTIVE: The objective was to
      determine whether this diet shift can be an effective tool in environmental
      protection. DESIGN: The 3 features by which this diet shift affects the
      environment-composition, transport (import), and type of production
      (organic/conventional)-were separately investigated by using life cycle
      assessment. RESULTS: When both diet composition and transport were taken into
      account, the NND reduced the environmental impact relative to the ADD measured by
      all 16 impact categories. The socioeconomic savings related to this diet shift
      was ?266/person per year, or 32% of the overall environmental cost of the ADD.
      When the actual 8% content of organic produce in the ADD and the 84% content of
      organic produce in the investigated recipe-based NND were also taken into
      account, the NND reduced the environmental impact relative to the ADD measured by
      only 10 of the 16 impact categories whereas 6 were increased. The socioeconomic
      savings related to the diet shift were lowered to ?42/person per year, or 5% of
      the overall environmental cost of the ADD. CONCLUSION: Reducing the content of
      meat and excluding most long-distance imports were of substantial environmental
      and socioeconomic advantage to the NND when compared with the ADD, whereas
      including high amounts of organic produce was a disadvantage.

PMID- 24670944
TI  - A narrow view of optimal weight for health generates the obesity paradox.

PMID- 24670945
TI  - Do impaired memory and body weight regulation originate in childhood with diet
      induced hippocampal dysfunction?

PMID- 24670946
TI  - Snacks containing whey protein and polydextrose induce a sustained reduction in
      daily energy intake over 2 wk under free-living conditions.
AB  - BACKGROUND: The manipulation of the composition of foods consumed as between-meal
      snacks may aid daily energy restriction. OBJECTIVES: We compared the effects of
      the consumption of 2 energy-matched snack bars on appetite, energy intake (EI),
      and metabolic and endocrine responses. In addition, we investigated whether the
      acute effects of the consumption of snacks were maintained under free-living
      conditions and whether the habitual daily consumption of the snack over 14 d
      influenced these effects. DESIGN: Ten lean men [mean +/- SD age: 30.7 +/- 9.7 y;
      body mass index (in kg/m(2)): 23.2 +/- 2.8] consumed a whey protein and
      polydextrose (PPX) snack bar or an isoenergetic control snack bar as a
      midmorning, between-meal snack for 14 consecutive days in a double-blind,
      randomized, crossover design. The two 14-d intervention phases were separated by
      a 14-d washout period. On the first (day 1) and last (day 15) days of each
      intervention phase, appetite, food intake, and blood metabolite and endocrine
      responses were assessed under laboratory conditions. Free-living EI was recorded
      on days 4, 8, and 12 of interventions. RESULTS: Total daily EI was significantly
      lower when the PPX snack was consumed during experimental days (10,149 +/- 831
      compared with 11,931 +/- 896 kJ; P < 0.01), and daily EI remained lower when the
      PPX snack was consumed during the free-living part of the intervention (7904 +/-
      610 compared with 9041 +/- 928 kJ; P < 0.05). The PPX snack was associated with
      lower glucose and ghrelin and higher glucagon-like peptide 1 and peptide tyrosine
      tyrosine responses. CONCLUSION: The manipulation of the composition of foods
      consumed as snacks is an effective way to limit subsequent EI. This trial was
      registered at clinicaltrials.gov as NCT01927926.

PMID- 24670949
TI  - Intra-grain perpendicular percolated L11 CoPt thin films.
AB  - Ultrathin percolated high-Ku magnetic films with thicknesses of 2 nm are realized
      simply by using sputter deposition and post annealing. L11 CoPt:MgO, with Ku on
      the order of 10(7) erg cm(-3), was deposited on a MgO(111) substrate at 350 
      degrees C, followed by post annealing to induce complete segregation of the added
      MgO dopants. The optimized film shows significant enhancement of the out-of-plane
      coercivity, approximately an order of magnitude greater than that of the CoPt
      binary film, a remanence ratio close to unity, considerably reduced in-plane
      magnetization, sharp perpendicular magnetic reversal, and reduced surface
      roughness in the range of a few angstroms. Microstructure results indicate that
      MgO precipitates into grains within the interconnected L11 grains after
      appropriate post annealing. The MgO grains, with sizes in the range 2-7 nm, form
      coherent interfaces to the CoPt matrix and penetrate through the whole depth of
      the film. The development of ideal non-magnetic domain wall pinning sites
      explains the optimization of the perpendicular magnetic properties. The
      advantages of a simple fabrication process, a thin film layer structure, and
      remarkable enhancement of the magnetic characteristics demanded by ultrahigh
      density recording reveal its potential for practical applications.

PMID- 24670947
TI  - Footprints of directional selection in wild Atlantic salmon populations: evidence
      for parasite-driven evolution?
AB  - Mechanisms of host-parasite co-adaptation have long been of interest in
      evolutionary biology; however, determining the genetic basis of parasite
      resistance has been challenging. Current advances in genome technologies provide
      new opportunities for obtaining a genome-scale view of the action of parasite
      driven natural selection in wild populations and thus facilitate the search for
      specific genomic regions underlying inter-population differences in pathogen
      response. European populations of Atlantic salmon (Salmo salar L.) exhibit
      natural variance in susceptibility levels to the ectoparasite Gyrodactylus
      salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are
      therefore a good model for studying the evolution of virulence and resistance.
      However, distinguishing the molecular signatures of genetic drift and environment
      associated selection in small populations such as land-locked Atlantic salmon
      populations presents a challenge, specifically in the search for pathogen-driven
      selection. We used a novel genome-scan analysis approach that enabled us to i)
      identify signals of selection in salmon populations affected by varying levels of
      genetic drift and ii) separate potentially selected loci into the categories of
      pathogen (G. salaris)-driven selection and selection acting upon other
      environmental characteristics. A total of 4631 single nucleotide polymorphisms
      (SNPs) were screened in Atlantic salmon from 12 different northern European
      populations. We identified three genomic regions potentially affected by parasite
      driven selection, as well as three regions presumably affected by salinity-driven
      directional selection. Functional annotation of candidate SNPs is consistent with
      the role of the detected genomic regions in immune defence and, implicitly, in
      osmoregulation. These results provide new insights into the genetic basis of
      pathogen susceptibility in Atlantic salmon and will enable future searches for
      the specific genes involved. 

PMID- 24670950
TI  - Rapid detection of terbufos in stomach contents using desorption electrospray
      ionization mass spectrometry.
AB  - Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging
      analytical technique that permits the rapid and direct analysis of biological or
      environmental samples under ambient conditions. Highlighting the versatility of
      this technique, DESI-MS has been used for the rapid detection of illicit drugs,
      chemical warfare agents, agricultural chemicals, and pharmaceuticals from a
      variety of sample matrices. In diagnostic veterinary toxicology, analyzing
      samples using traditional analytical instrumentation typically includes extensive
      sample extraction procedures, which can be time consuming and labor intensive.
      Therefore, efforts to expedite sample analyses are a constant goal for diagnostic
      toxicology laboratories. In the current report, DESI-MS was used to directly
      analyze stomach contents from a dog exposed to the organophosphate insecticide
      terbufos. The total DESI-MS analysis time required to confirm the presence of
      terbufos and diagnose organophosphate poisoning in this case was approximately 5
      min. This highlights the potential of this analytical technique in the field of
      veterinary toxicology for the rapid diagnosis and detection of toxicants in
      biological samples.

PMID- 24670948
TI  - Hepatic IRE1alpha regulates fasting-induced metabolic adaptive programs through
      the XBP1s-PPARalpha axis signalling.
AB  - Although the mammalian IRE1alpha-XBP1 branch of the cellular unfolded protein
      response has been implicated in glucose and lipid metabolism, the exact metabolic
      role of IRE1alpha signalling in vivo remains poorly understood. Here we show that
      hepatic IRE1alpha functions as a nutrient sensor that regulates the metabolic
      adaptation to fasting. We find that prolonged deprivation of food or consumption
      of a ketogenic diet activates the IRE1alpha-XBP1 pathway in mouse livers.
      Hepatocyte-specific abrogation of Ire1alpha results in impairment of fatty acid
      beta-oxidation and ketogenesis in the liver under chronic fasting or ketogenic
      conditions, leading to hepatosteatosis; liver-specific restoration of XBP1s
      reverses the defects in IRE1alpha null mice. XBP1s directly binds to and
      activates the promoter of PPARalpha, the master regulator of starvation
      responses. Hence, our results demonstrate that hepatic IRE1alpha promotes the
      adaptive shift of fuel utilization during starvation by stimulating mitochondrial
      beta-oxidation and ketogenesis through the XBP1s-PPARalpha axis. 

PMID- 24670951
TI  - Evaluating micronutrient concentrations in liver samples from abortions,
      stillbirths, and neonatal and postnatal losses in beef calves.
AB  - The primary objective of the current study was to describe micronutrient
      concentrations in livers collected during postmortem examination from 501 beef
      calves and fetuses in western Canada. The most frequently identified deficiencies
      based on reported ranges for aborted fetuses were magnesium, copper, and vitamin
      E. For stillborn, neonatal, and postnatal calves, the most common deficiencies
      were magnesium, vitamin A, and vitamin E. However, for calves that died after 3
      days of age, selenium deficiency was also very likely. Concentrations of all
      micronutrients examined in the study except zinc (P = 0.85) were different among
      fetuses, stillbirths, and neonatal and postnatal losses. This included liver
      selenium, copper, manganese, molybdenum, iron, magnesium, vitamin A, and vitamin
      E (P < 0.01). The percentiles of micronutrient concentrations for each age group,
      empirical prediction intervals for individual calves, and model predicted
      confidence intervals to compare with average concentrations from groups of calves
      were summarized for each age group. Information on cow, calf, and herd management
      attributes were available for 221 samples from 106 herds collected as part of
      study 1. Cow age, supplementation history, water quality, and herd location were
      associated with the concentration of iron, zinc, and molybdenum. The current
      study is unique in the number of samples included from young calves that were
      submitted as part of routine surveillance and not based on suspicion of either
      deficiency or toxicity. Most previous studies have been focused on older animals
      or fetuses and have contained a mix of beef and dairy animals with little or no
      information on their supplementation history.

PMID- 24670952
TI  - Amino acid differences in cat adrenocorticotropin account for the inability of a
      human-based immunoradiometric assay to detect the molecule in cat plasma.
AB  - A commercial immunoradiometric assay kit designed for the measurement of
      endogenous adrenocorticotropin (ACTH) concentrations in human plasma does not
      detect the molecule in plasma samples from cats. It was hypothesized that the
      inability of the assay to detect the molecule was related to variation(s) in the
      amino acid sequence of cat ACTH, compared with human ACTH. Cat ACTH complementary
      DNA was cloned from pituitary tissue and sequenced. The deduced structure showed
      amino acid differences from the human molecule with cat ACTH having a valine
      instead of alanine at amino acid 32 and a threonine instead of alanine at amino
      acid 34. Cat and human ACTH were synthesized along with 2 modified peptides
      containing alanine substitutions at cat ACTH 32 and 34. Only the human ACTH was
      detected using the commercial kit, indicating that an epitope recognized by one
      of the antibodies in the assay requires the presence of 2 alanines near the C
      terminus of the molecule.

PMID- 24670953
TI  - Canine parvovirus 2c infection in a cat with severe clinical disease.
AB  - Canine parvovirus 2 (CPV-2) is considered the main pathogen responsible for acute
      gastroenteritis in dogs, causing vomiting and hemorrhagic enteritis mainly.
      However, infection in cats by CPV variants causes clinical signs similar to
      Feline panleukopenia virus. The current study reports a case of CPV-2c in a
      domestic cat, in Portugal. The findings suggest that more surveys are needed to
      know the true prevalence and significance of cats in CPV epidemiology worldwide.

PMID- 24670954
TI  - Enzyme-linked immunosorbent assay for coproantigen detection of Trichuris vulpis
      in dogs.
AB  - Infections with Trichuris vulpis, the canine whipworm, may be challenging to
      diagnose even though characteristic bipolar eggs are shed by mature worms and may
      be recovered from feces. Decreased detection sensitivities because of using
      flotation solutions with specific gravities <1.3 and a lengthy prepatent period
      can lessen the diagnostician's ability to detect infection. Coproantigen
      detection in feces is becoming an accepted form of diagnosing parasitic
      infections and can circumvent some of the factors that affect egg recovery. The
      development of an enzyme-linked immunosorbent assay (ELISA) for the detection of
      whipworm-specific coproantigens in the feces of dogs with experimental and
      natural T. vulpis infections is reported herein. Whipworm-specific coproantigens
      were evidenced in feces from experimentally infected dogs using the newly
      developed ELISA starting as early as day 23 postinfection, while eggs were not
      detected in feces until day 69. In addition, 1,156 field fecal samples were
      tested using fecal flotation methods and the newly developed whipworm ELISA. Of
      these, 27 samples were found by flotation to be whipworm egg positive, while 35
      had detectable antigen on the ELISA. Discrepant results were obtained in 12
      samples; 2 egg-positive samples tested ELISA negative, and 10 ELISA-positive
      samples did not contain detectable egg levels. Using the fecal ELISA for the
      detection of whipworms in dogs should allow for earlier detection of infection,
      aid the identification of cases in the face of low egg shedding, and increase
      detection sensitivity as most commercial laboratories are using flotation
      solutions not optimal for T. vulpis egg detection.

PMID- 24670955
TI  - The Ca2+-activated K+ current of human sperm is mediated by Slo3.
AB  - Sperm are equipped with a unique set of ion channels that orchestrate
      fertilization. In mouse sperm, the principal K(+) current (IKSper) is carried by
      the Slo3 channel, which sets the membrane potential (Vm) in a strongly pHi
      dependent manner. Here, we show that IKSper in human sperm is activated weakly by
      pHi and more strongly by Ca(2+). Correspondingly, Vm is strongly regulated by
      Ca(2+) and less so by pHi. We find that inhibitors of Slo3 suppress human IKSper,
      and we identify the Slo3 protein in the flagellum of human sperm. Moreover,
      heterologously expressed human Slo3, but not mouse Slo3, is activated by Ca(2+)
      rather than by alkaline pHi; current-voltage relations of human Slo3 and human
      IKSper are similar. We conclude that Slo3 represents the principal K(+) channel
      in human sperm that carries the Ca(2+)-activated IKSper current. We propose that,
      in human sperm, the progesterone-evoked Ca(2+) influx carried by voltage-gated
      CatSper channels is limited by Ca(2+)-controlled hyperpolarization via Slo3. DOI:
      http://dx.doi.org/10.7554/eLife.01438.001. 

PMID- 24670956
TI  - Evolution of insect olfactory receptors.
AB  - The olfactory sense detects a plethora of behaviorally relevant odor molecules;
      gene families involved in olfaction exhibit high diversity in different animal
      phyla. Insects detect volatile molecules using olfactory (OR) or ionotropic
      receptors (IR) and in some cases gustatory receptors (GRs). While IRs are
      expressed in olfactory organs across Protostomia, ORs have been hypothesized to
      be an adaptation to a terrestrial insect lifestyle. We investigated the olfactory
      system of the primary wingless bristletail Lepismachilis y-signata
      (Archaeognatha), the firebrat Thermobia domestica (Zygentoma) and the neopteran
      leaf insect Phyllium siccifolium (Phasmatodea). ORs and the olfactory coreceptor
      (Orco) are with very high probability lacking in Lepismachilis; in Thermobia we
      have identified three Orco candidates, and in Phyllium a fully developed OR/Orco
      based system. We suggest that ORs did not arise as an adaptation to a terrestrial
      lifestyle, but evolved later in insect evolution, with Orco being present before
      the appearance of ORs. DOI: http://dx.doi.org/10.7554/eLife.02115.001. 

PMID- 24670957
TI  - Direct and indirect effects of PCV13 on nasopharyngeal carriage of PCV13 unique
      pneumococcal serotypes in Massachusetts' children.
AB  - BACKGROUND: The direct impact of 13-valent pneumococcal conjugate vaccine (PCV13)
      on colonization with unique PCV13 serotypes and the uptake of vaccine necessary
      to create indirect protection in nonimmunized children were assessed. METHODS:
      Carriage surveillance among children <60 months began in July 2010 at a pediatric
      practice in Boston, MA. Children had nasopharyngeal cultures and parents
      completed questionnaires detailing demographics and health status. Concurrently,
      we monitored uptake of PCV13 in children in the community. Children were
      classified as "presumed immune" or "presumed nonimmune" based on age and PCV13
      immunizations received. We assessed trends using adjusted prevalence rates
      calculated within rolling, 25-week, consecutive intervals. RESULTS: Between July
      2010 and June 2012, 1050 S. pneumoniae isolates were recovered from 1042
      children. Eighty-nine isolates (8.5%) were 1 of 6 unique PCV13 serotypes. The
      expected fall/winter peak in PCV13 carriage was observed in nonimmune children,
      but was blunted in immune children. There was a 74% reduction in PCV13
      colonization in immune compared with nonimmune children. We document a 50% or
      more decline in the PCV13 carriage in nonimmune children, at the time when the
      approximately 75% or more of the community children had received PCV13 and were
      considered immune. During the study, the difference in PCV13 serotype
      colonization prevalence in nonimmune and immune children disappeared. No evidence
      of replacement has been observed to date. CONCLUSIONS: The direct impact of PCV13
      on colonization was demonstrated. Evidence of indirect protection in unimmunized
      (nonimmune) children was observed as vaccine uptake reached 75% in the target
      community.

PMID- 24670958
TI  - A reconsideration of the correlation between veteran status and firearm suicide
      in the general population.
AB  - BACKGROUND: The relationship between veteran status and firearm suicide has been
      evaluated previously, but multiple sources of bias limit conclusions. This study
      aimed to clarify the relationship between a history of military service and
      firearm suicide. METHODS: Data obtained from suicide death certificates from nine
      states (1999-2009) were analysed. History of military service was validated using
      data obtained from the Department of Veterans Affairs and Department of Defense.
      Modified Poisson Regression with robust SEs was used to compute adjusted
      prevalence ratios for the common outcome of firearm use among suicide decedents.
      RESULTS: Male veteran suicide decedents were 6% more likely to use firearms, and
      female veteran suicide decedents were 18% more likely to use firearms compared
      with their non-veteran peers. CONCLUSIONS: Prior estimates based on logistic
      regression and death certificate reporting of veteran status may have
      overestimated the relationship between veteran status and firearm use among
      suicide decedents.

PMID- 24670959
TI  - How well do principal diagnosis classifications predict disability 12 months
      postinjury?
AB  - BACKGROUND: The application of disability weights by nature of injury is central
      to the calculation of disability-adjusted life years (DALYs). Such weights should
      represent injury diagnosis groups that demonstrate homogeneity in disability
      outcomes. Existing classifications have not used empirical data in their
      development to inform groups that are homogeneous for disability outcomes,
      limiting the capacity to make informed recommendations for best practice in
      measuring injury burden. METHODS: The Validating and Improving injury Burden
      Estimates (Injury-VIBES) Study includes pooled data from over 30 000 injured
      participants recruited to six cohort studies. The International Classification of
      Disease 10th Revision (ICD-10) diagnosis codes were mapped to existing injury
      burden study groupings and prediction models were developed to measure the
      capacity of the injury groupings and ICD-10 diagnoses to predict disability
      outcomes at 12 months. Models were adjusted for age, gender and data source and
      investigated for discrimination using area under the receiver operating
      characteristic curve (AUC) and calibration using Hosmer-Lemeshow statistics and
      calibration curves. RESULTS: Discrimination and calibration of models varied
      depending on the outcome measured. Models using full four-character ICD-10
      diagnosis codes, rather than groupings of codes, demonstrated the highest
      discrimination ranging from an AUC (95% CI) of 0.627 (0.618 to 0.635) for the
      pain or discomfort item of the EQ-5D to 0.847 (0.841 to 0.853) for the extended
      Glasgow Outcome Scale independent living outcome. However, gain over other
      groupings was marginal. CONCLUSIONS: Prediction performance was best for measures
      of function such as independent living, mobility and self-care. The
      classifications were poorer predictors of anxiety/depression and pain/discomfort.
      There was no clearly superior classification.

PMID- 24670960
TI  - Re-repair of ruptured primary flexor tendon repairs in Zones I and II of the
      fingers in children.
AB  - The aetiology, management, and results of acute rupture of primary flexor tendon
      repairs in Zones I and II of the fingers in children have not been previously
      investigated. The author reports on a personal series of 10 children treated over
      a period of 13 years. The aetiology is different when compared with adults:
      children less than 5 years of age usually rupture their primary repairs whilst
      the hand is completely immobilized in a cast; whereas teenagers usually rupture
      their tendons when falling down while playing. In the current series, direct re
      repair was performed without lengthening at the musculo-tendinous junction, and
      no free tendon grafts were used. The results were worse than other paediatric
      series of primary flexor tendon repairs. Using the Strickland-Glogovac criteria,
      there was only one excellent outcome, the remaining nine being either a good (n =
      5) or fair (n = 4) outcome. 

PMID- 24670961
TI  - Prevalence of autism spectrum disorder among children aged 8 years - autism and
      developmental disabilities monitoring network, 11 sites, United States, 2010.
AB  - PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2010.
      DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring
      (ADDM) Network is an active surveillance system in the United States that
      provides estimates of the prevalence of ASD and other characteristics among
      children aged 8 years whose parents or guardians live in 11 ADDM sites in the
      United States. ADDM surveillance is conducted in two phases. The first phase
      consists of screening and abstracting comprehensive evaluations performed by
      professional providers in the community. Multiple data sources for these
      evaluations include general pediatric health clinics and specialized programs for
      children with developmental disabilities. In addition, most ADDM Network sites
      also review and abstract records of children receiving special education services
      in public schools. The second phase involves review of all abstracted evaluations
      by trained clinicians to determine ASD surveillance case status. A child meets
      the surveillance case definition for ASD if a comprehensive evaluation of that
      child completed by a qualified professional describes behaviors consistent with
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions:
      autistic disorder, pervasive developmental disorder-not otherwise specified
      (including atypical autism), or Asperger disorder. This report provides updated
      prevalence estimates for ASD from the 2010 surveillance year. In addition to
      prevalence estimates, characteristics of the population of children with ASD are
      described. RESULTS: For 2010, the overall prevalence of ASD among the ADDM sites
      was 14.7 per 1,000 (one in 68) children aged 8 years. Overall ASD prevalence
      estimates varied among sites from 5.7 to 21.9 per 1,000 children aged 8 years.
      ASD prevalence estimates also varied by sex and racial/ethnic group.
      Approximately one in 42 boys and one in 189 girls living in the ADDM Network
      communities were identified as having ASD. Non-Hispanic white children were
      approximately 30% more likely to be identified with ASD than non-Hispanic black
      children and were almost 50% more likely to be identified with ASD than Hispanic
      children. Among the seven sites with sufficient data on intellectual ability, 31%
      of children with ASD were classified as having IQ scores in the range of
      intellectual disability (IQ <=70), 23% in the borderline range (IQ = 71-85), and
      46% in the average or above average range of intellectual ability (IQ >85). The
      proportion of children classified in the range of intellectual disability
      differed by race/ethnicity. Approximately 48% of non-Hispanic black children with
      ASD were classified in the range of intellectual disability compared with 38% of
      Hispanic children and 25% of non-Hispanic white children. The median age of
      earliest known ASD diagnosis was 53 months and did not differ significantly by
      sex or race/ethnicity. INTERPRETATION: These findings from CDC's ADDM Network,
      which are based on 2010 data reported from 11 sites, provide updated population
      based estimates of the prevalence of ASD in multiple communities in the United
      States. Because the ADDM Network sites do not provide a representative sample of
      the entire United States, the combined prevalence estimates presented in this
      report cannot be generalized to all children aged 8 years in the United States
      population. Consistent with previous reports from the ADDM Network, findings from
      the 2010 surveillance year were marked by significant variations in ASD
      prevalence by geographic area, sex, race/ethnicity, and level of intellectual
      ability. The extent to which this variation might be attributable to diagnostic
      practices, underrecognition of ASD symptoms in some racial/ethnic groups,
      socioeconomic disparities in access to services, and regional differences in
      clinical or school-based practices that might influence the findings in this
      report is unclear. PUBLIC HEALTH ACTION: ADDM Network investigators will continue
      to monitor the prevalence of ASD in select communities, with a focus on exploring
      changes within these communities that might affect both the observed prevalence
      of ASD and population-based characteristics of children identified with ASD.
      Although ASD is sometimes diagnosed by 2 years of age, the median age of the
      first ASD diagnosis remains older than age 4 years in the ADDM Network
      communities. Recommendations from the ADDM Network include enhancing strategies
      to address the need for 1) standardized, widely adopted measures to document ASD
      severity and functional limitations associated with ASD diagnosis; 2) improved
      recognition and documentation of symptoms of ASD, particularly among both boys
      and girls, children without intellectual disability, and children in all
      racial/ethnic groups; and 3) decreasing the age when children receive their first
      evaluation for and a diagnosis of ASD and are enrolled in community-based support
      systems.

PMID- 24670962
TI  - A canine case of primary intra-right atrial paraganglioma.
AB  - An 11-year-old mixed breed dog was presented with signs of anorexia. Radiographic
      and ultrasound examinations revealed a large mass in the heart, between the right
      atrium and the right ventricle. Upon gross inspection, a multilobulated tumor
      arising from the right atrial wall and occupying the right atrium was identified.
      Microscopical analysis demonstrated that this tumor consisted of neoplastic cells
      with granular cytoplasm, which were separated into nests by fine fibrovascular
      stroma and were negative for Grimelius's method. Immunohistochemical examinations
      revealed that the neoplastic cells expressed chromogranin A, synaptophysin and
      neuron specific enolase. Electron microscopy revealed that the cytoplasm of the
      neoplastic cells held secretory granules. Based on these pathological findings,
      the tumor was diagnosed as a paraganglioma. This report is a rare case of primary
      paraganglioma deriving from the right atrium and provides a detailed
      characterization of its morphological features. 

PMID- 24670963
TI  - Bone regeneration by the combined use of tetrapod-shaped calcium phosphate
      granules with basic fibroblast growth factor-binding ion complex gel in canine
      segmental radial defects.
AB  - The effect of tetrapod-shaped alpha tricalcium phosphate granules
      (Tetrabones((r)) [TB]) in combination with basic fibroblast growth factor (bFGF)
      binding ion complex gel (f-IC gel) on bone defect repair was examined. Bilateral
      segmental defects 20-mm long were created in the radius of 5 dogs, stabilized
      with a plate and screws and implanted with 1 of the following: TB (TB group), TB
      and bFGF solution (TB/f group), and TB and f-IC gel (TB/f-IC group). Dogs were
      euthanized 4 weeks after surgery. Radiographs showed well-placed TB granules in
      the defects and equal osseous callus formation in all the groups.
      Histomorphometry revealed that the number of vessels and volume of new bone in
      the TB/f-IC group were significantly higher than those in the other groups.
      However, no significant differences in neovascularization and new bone formation
      were observed between the TB/f and TB groups. Furthermore, no significant
      difference in the lamellar bone volume or rate of mineral apposition was observed
      among groups. These results suggest that increased bone formation might have been
      because of the promotion of neovascularization by the f-IC gel. Therefore, the
      combinatorial method may provide a suitable scaffold for bone regeneration in
      large segmental long bone defects. 

PMID- 24670964
TI  - Fungal invasion of epithelial cells.
AB  - Interaction between host cells and invasive Candida plays a large role in the
      pathogenicity of Candida species. Fungal-induced endocytosis and active
      penetration are the two distinct, yet complementary invasion mechanisms of
      invasive candidiasis. Induced endocytosis is a microorganism-triggered,
      epithelial-driven, clathrin-mediated and actin-dependent process. During the
      fundamental pathological process of induced endocytosis, invasins (Als3 and
      Ssa1), which mediate the binding of host epithelial surface proteins, are
      expressed by Candida species on the hyphal surface. Sequentially, the interaction
      between invasins and host epithelial surface proteins stimulates the recruitment
      of clathrin, dynamin and cortactin to the sites where Candida enters epithelial
      cells, which in turn induce the actin cytoskeleton reorganization. Actin
      cytoskeleton provides the force required for fungal internalization. Parallely,
      active penetration of Candida can directly pass through epithelial cells possibly
      due to progressive elongation of hyphae and physical forces. Several molecules,
      such as secreted hydrolases and Als3, can affect the protective barrier of the
      epithelium and make Candida actively penetrate into epithelial cells through
      intercellular gaps of epithelial layers.

PMID- 24670965
TI  - Systematic reviews of animal studies; missing link in translational research?
AB  - BACKGROUND: The methodological quality of animal studies is an important factor
      hampering the translation of results from animal studies to a clinical setting.
      Systematic reviews of animal studies may provide a suitable method to assess and
      thereby improve their methodological quality. OBJECTIVES: The aims of this study
      were: 1) to evaluate the risk of bias assessment in animal-based systematic
      reviews, and 2) to study the internal validity of the primary animal studies
      included in these systematic reviews. DATA SOURCES: We systematically searched
      Pubmed and Embase for SRs of preclinical animal studies published between 2005
      and 2012. RESULTS: A total of 91 systematic reviews met our inclusion criteria.
      The risk of bias was assessed in 48 (52.7%) of these 91 systematic reviews.
      Thirty-three (36.3%) SRs provided sufficient information to evaluate the internal
      validity of the included studies. Of the evaluated primary studies, 24.6% was
      randomized, 14.6% reported blinding of the investigator/caretaker, 23.9% blinded
      the outcome assessment, and 23.1% reported drop-outs. CONCLUSIONS: To improve the
      translation of animal data to clinical practice, systematic reviews of animal
      studies are worthwhile, but the internal validity of primary animal studies needs
      to be improved. Furthermore, risk of bias should be assessed by systematic
      reviews of animal studies to provide insight into the reliability of the
      available evidence.

PMID- 24670966
TI  - NET formation induced by Pseudomonas aeruginosa cystic fibrosis isolates measured
      as release of myeloperoxidase-DNA and neutrophil elastase-DNA complexes.
AB  - Cystic fibrosis (CF) airway disease is characterized by Pseudomonas aeruginosa
      infection and recruitment of neutrophil granulocytes. Neutrophil granule
      components (myeloperoxidase (MPO), human neutrophil elastase (HNE)),
      extracellular DNA and P. aeruginosa can all be found in the CF respiratory tract
      and have all been associated with worsening CF lung function. Pseudomonas-induced
      formation of neutrophil extracellular traps (NETs) offers a likely mechanism for
      release of MPO, HNE and DNA from neutrophils. NETs are composed of a DNA backbone
      decorated with granule proteins like MPO and HNE. Here we sought to examine
      whether CF clinical isolates of Pseudomonas are capable of inducing NET release
      from human neutrophil granulocytes. We used two methods to quantify NETs. We
      modified a previously employed ELISA that detects MPO-DNA complexes and
      established a new HNE-DNA ELISA. We show that these methods reliably quantify MPO
      DNA and HNE-DNA complexes, measures of NET formation. We have found that CF
      isolates of P. aeruginosa stimulate robust respiratory burst and NET release in
      human neutrophils. By comparing paired "early" and "late" bacterial isolates
      obtained from the same CF patient we have found that early isolates induced
      significantly more NET release than late isolates. Our data support that
      Pseudomonas-induced NET release represents an important mechanism for release of
      neutrophil-derived CF inflammatory mediators, and confirm that decreased
      induction of NET formation is required for long-term adaptation of P. aeruginosa
      to CF airways. 

PMID- 24670967
TI  - Postradiation damage to the pelvic girdle in cervical cancer patients: is
      intensity-modulated radiation therapy safer than conventional radiation?
AB  - OBJECTIVES: Intensity-modulated radiation therapy (IMRT) is frequently utilized
      in the treatment of cervical cancer. Our study compared instances of pelvic
      fractures, osteonecrosis, and osteomyelitis posttreatment with conventional
      radiation therapy (RT) versus IMRT in patients with cervical carcinomas. METHODS:
      Eighty-three patients primarily treated with IMRT were case matched with 83
      historical control subjects treated with conventional RT. Pretreatment and
      posttreatment computed tomography scans were reviewed. Logistic regression
      analysis was utilized to examine the effects of treatment type (conventional RT
      vs IMRT) on the occurrence of posttreatment pelvic bony structure complications
      while adjusting for confounders. RESULTS: In the IMRT group, 3 (4%) of 83
      patients developed posttreatment sacral fractures (median follow-up, 51 months).
      In the conventional RT group, there were 14 pelvic girdle complications (17%): 9
      fractures, 2 cases of osteonecrosis, and 3 cases of osteomyelitis (median follow
      up, 43.5 months; odds ratio, 4.49 for conventional vs IMRT groups, P = 0.01; 95%
      confidence interval, 1.4-14.1). In addition, there were 4 cases of posttreatment
      osteoporosis in the conventional RT group. All patients with complications in the
      IMRT group and 11 of 13 in the conventional RT group were symptomatic.
      CONCLUSIONS: Intensity-modulated radiation therapy is associated with a lower
      risk for pelvic girdle complications than conventional RT.

PMID- 24670968
TI  - A novel approach to the discovery of survival biomarkers in glioblastoma using a
      joint analysis of DNA methylation and gene expression.
AB  - Glioblastoma multiforme (GBM) is the most aggressive of all brain tumors, with a
      median survival of less than 1.5 years. Recently, epigenetic alterations were
      found to play key roles in both glioma genesis and clinical outcome,
      demonstrating the need to integrate genetic and epigenetic data in predictive
      models. To enhance current models through discovery of novel predictive
      biomarkers, we employed a genome-wide, agnostic strategy to specifically capture
      both methylation-directed changes in gene expression and alternative associations
      of DNA methylation with disease survival in glioma. Human GBM-associated DNA
      methylation, gene expression, IDH1 mutation status, and survival data were
      obtained from The Cancer Genome Atlas. DNA methylation loci and expression probes
      were paired by gene, and their subsequent association with survival was
      determined by applying an accelerated failure time model to previously published
      alternative and expression-based association equations. Significant associations
      were seen in 27 unique methylation/expression pairs with expression-based,
      alternative, and combinatorial associations observed (10, 13, and 4 pairs,
      respectively). The majority of the predictive DNA methylation loci were located
      within CpG islands, and all but three of the locus pairs were negatively
      correlated with survival. This finding suggests that for most loci,
      methylation/expression pairs are inversely related, consistent with methylation
      associated gene regulatory action. Our results indicate that changes in DNA
      methylation are associated with altered survival outcome through both coordinated
      changes in gene expression and alternative mechanisms. Furthermore, our approach
      offers an alternative method of biomarker discovery using a priori gene pairing
      and precise targeting to identify novel sites for locus-specific therapeutic
      intervention. 

PMID- 24670969
TI  - Dietary arginine supplementation of mice alters the microbial population and
      activates intestinal innate immunity.
AB  - Currently, little is known about the function of arginine in the homeostasis of
      the intestinal immune system. This study was conducted to test the hypothesis
      that dietary arginine supplementation may alter intestinal microbiota and innate
      immunity in mice. Mice were fed a basal diet (containing 0.93% l-arginine; grams
      per gram) or the basal diet supplemented with 0.5% l-arginine for 14 d. We
      studied the composition of intestinal microbiota, the activation of innate
      immunity, and the expression of toll-like receptors (Tlrs), proinflammatory
      cytokines, and antimicrobials in the jejunum, ileum, or colon of mice. Signal
      transduction pathway activation in the jejunum and ileum, including TLR4-nuclear
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), mitogen
      activated protein kinase (MAPK), and phosphoinositide-3 kinase (PI3K)/PI3K
      protein kinase B (Akt), was analyzed by Western blotting. Quantitative polymerase
      chain reaction analysis revealed that arginine supplementation induced (P < 0.05)
      a shift in the Firmicutes-to-Bacteroidetes ratio to favor Bacteroidetes in the
      jejunum (0.33 +/- 0.04 vs. 1.0 +/- 0.22) and ileum (0.20 +/- 0.08 vs. 1.0 +/-
      0.27) compared with the control group. This finding coincided with greater (P <
      0.05) activation of the innate immune system, including TLR signaling, as well as
      expression of proinflammatory cytokines, secretory immunoglobulin A, mucins, and
      Paneth antimicrobials in the jejunum and ileum. Finally, arginine supplementation
      reduced (P < 0.05) expression of the proteins for NF-kappaB, MAPK, and PI3K-Akt
      signaling pathways but activated (P < 0.05) p38 and c-Jun N-terminal protein
      kinase in the jejunum and the ileum, respectively. Collectively, dietary arginine
      supplementation of mice changes the intestinal microbiota, contributing to the
      activation of intestinal innate immunity through NF-kappaB, MAPK, and PI3K
      phosphorylated Akt signaling pathways. 

PMID- 24670970
TI  - Freeze-dried strawberries lower serum cholesterol and lipid peroxidation in
      adults with abdominal adiposity and elevated serum lipids.
AB  - Dietary flavonoid intake, especially berry flavonoids, has been associated with
      reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few
      clinical studies have examined the effects of dietary berries on CVD risk
      factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve
      lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid
      oxidation in adults with abdominal adiposity and elevated serum lipids. In a
      randomized dose-response controlled trial, 60 volunteers [5 men and 55 women;
      aged 49 +/- 10 y; BMI: 36 +/- 5 kg/m(2) (means +/- SDs)] were assigned to consume
      1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2)
      low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose
      control (HD-C). Control beverages were matched for calories and total fiber.
      Blood draws, anthropometrics, blood pressure, and dietary data were collected at
      screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed
      significantly greater decreases in serum total and LDL cholesterol and nuclear
      magnetic resonance (NMR)-derived small LDL particle concentration in HD-FDS [33
      +/- 6 mg/dL, 28 +/- 7 mg/dL, and 301 +/- 78 nmol/L, respectively (means +/-
      SEMs)] vs. LD-FDS (-3 +/- 11 mg/dL, -3 +/- 9 mg/dL, and -28 +/- 124 nmol/L,
      respectively) over 12 wk (0-12 wk; all P < 0.05). Compared with controls, only
      the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD
      C (0.7 +/- 12 and 1.4 +/- 9 mg/dL, respectively) over 12 wk (0-12 wk; all P <
      0.05). Both doses of strawberries showed a similar decrease in serum
      malondialdehyde at 12 wk (LD-FDS: 1.3 +/- 0.2 MUmol/L; HD-FDS: 1.2 +/- 0.1
      MUmol/L) vs. controls (LD-C: 2.1 +/- 0.2 MUmol/L; HD-C: 2.3 +/- 0.2 MUmol/L) (P <
      0.05). In general, strawberry intervention did not affect any measures of
      adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol
      and triglycerides, C-reactive protein, and adhesion molecules. Thus, HD-FDS
      exerted greater effects in lowering serum total and LDL cholesterol and NMR
      derived small LDL particles vs. LD-FDS in the 12-wk study. These findings warrant
      additional investigation in larger trials. This trial was registered at
      clinicaltrials.gov as NCT01883401. 

PMID- 24670971
TI  - Estimating upper bounds for occupancy and number of manatees in areas potentially
      affected by oil from the Deepwater Horizon oil spill.
AB  - The explosion of the Deepwater Horizon drilling platform created the largest
      marine oil spill in U.S. history. As part of the Natural Resource Damage
      Assessment process, we applied an innovative modeling approach to obtain upper
      estimates for occupancy and for number of manatees in areas potentially affected
      by the oil spill. Our data consisted of aerial survey counts in waters of the
      Florida Panhandle, Alabama and Mississippi. Our method, which uses a Bayesian
      approach, allows for the propagation of uncertainty associated with estimates
      from empirical data and from the published literature. We illustrate that it is
      possible to derive estimates of occupancy rate and upper estimates of the number
      of manatees present at the time of sampling, even when no manatees were observed
      in our sampled plots during surveys. We estimated that fewer than 2.4% of
      potentially affected manatee habitat in our Florida study area may have been
      occupied by manatees. The upper estimate for the number of manatees present in
      potentially impacted areas (within our study area) was estimated with our model
      to be 74 (95%CI 46 to 107). This upper estimate for the number of manatees was
      conditioned on the upper 95%CI value of the occupancy rate. In other words, based
      on our estimates, it is highly probable that there were 107 or fewer manatees in
      our study area during the time of our surveys. Because our analyses apply to
      habitats considered likely manatee habitats, our inference is restricted to these
      sites and to the time frame of our surveys. Given that manatees may be hard to
      see during aerial surveys, it was important to account for imperfect detection.
      The approach that we described can be useful for determining the best allocation
      of resources for monitoring and conservation. 

PMID- 24670972
TI  - Keeping your eyes continuously on the ball while running for catchable and
      uncatchable fly balls.
AB  - When faced with a fly ball approaching along the sagittal plane, fielders need
      information for the control of their running to the interception location. This
      information could be available in the initial part of the ball trajectory, such
      that the interception location can be predicted from its initial conditions.
      Alternatively, such predictive information is not available, and running to the
      interception location involves continuous visual guidance. The latter type of
      control would predict that fielders keep looking at the approaching ball for most
      of its flight, whereas the former type of control would fit with looking at the
      ball during the early part of the ball's flight; keeping the eyes on the ball
      during the remainder of its trajectory would not be necessary when the
      interception location can be inferred from the first part of the ball trajectory.
      The present contribution studied visual tracking of approaching fly balls.
      Participants were equipped with a mobile eye tracker. They were confronted with
      tennis balls approaching from about 20 m, and projected in such a way that some
      balls were catchable and others were not. In all situations, participants almost
      exclusively tracked the ball with their gaze until just before the catch or until
      they indicated that a ball was uncatchable. This continuous tracking of the ball,
      even when running close to their maximum speeds, suggests that participants
      employed continuous visual control rather than running to an interception
      location known from looking at the early part of the ball flight. 

PMID- 24670974
TI  - Justine effect: punishment of the unduly self-sacrificing cooperative
      individuals.
AB  - BACKGROUND: Allowing players to punish their opponents in Public Goods Game
      sustains cooperation within a group and thus brings advantage to the cooperative
      individuals. However, the possibility of punishment of the co-players can result
      in antisocial punishment, the punishment of those players who contribute the most
      in the group. To better understand why antisocial punishment exists, it must be
      determined who are the anti-social punishers and who are their primary targets.
      METHODS: For resolving these questions we increased the number of players in a
      group from usual four to twelve. Each group played six rounds of the standard
      Public Goods Game and six rounds of the Public Goods Game with punishment. Each
      player in each round received 20 CZK ($ 1.25). Players (N = 118) were rematched
      after each round so that they would not take into consideration opponents' past
      behavior. RESULTS: The amount of the punishment received correlated negatively
      with the contribution (rho = -0.665, p<0.001). However, this correlation was
      positive for players in the highest contributors-quartile (rho = 0.254, p<0.001).
      Therefore, the graph of relation between the contribution given and punishment
      obtained was U-shaped (R2 = 0.678, p<0.001) with the inflection point near the
      left boarder of the upper quartile. The antisocial punishment was present in all
      groups, and in eight out of ten groups the Justine Effect (the positive
      correlation between the contribution to the public pool and the risk of suffering
      punishment in the subpopulation of altruistic players) emerged. In our sample,
      22.5% subjects, all of them Free riders and low contributors, punished the
      altruistic players. CONCLUSIONS: The results of our experimental game-study
      revealed the existence of the Justine effect--the positive correlation between
      the contribution to the public pool by a subpopulation of the most altruistic
      players, and the amount of punishment these players obtained from free-riders.

PMID- 24670973
TI  - Contraceptive options and their associated estrogenic environmental loads:
      relationships and trade-offs.
AB  - This work explores the relationships between a user's choice of a given
      contraceptive option and the load of steroidal estrogens that can be associated
      with that choice. Family planning data for the USA served as a basis for the
      analysis. The results showed that collectively the use of contraception in the
      USA conservatively averts the release of approximately 4.8 tonnes of estradiol
      equivalents to the environment. 35% of the estrogenic load released over the
      course of all experienced pregnancies events and 34% the estrogenic load
      represented by all resultant legacies are a result of contraception failure and
      the non-use of contraception. A scenario analysis conducted to explore the
      impacts of discontinuing the use of ethinylestradiol-based oral contraceptives
      revealed that this would not only result in a 1.7-fold increase in the estrogenic
      loading of the users, but the users would also be expected to experience
      undesired family planning outcomes at a rate that is 3.3 times higher. Additional
      scenario analyses in which ethinylestradiol-based oral contraceptive users were
      modeled as having switched entirely to the use of male condoms, diaphragms or
      copper IUDs suggested that whether a higher or lower estrogenic load can be
      associated with the switching population depends on the typical failure rates of
      the options adopted following discontinuation. And, finally, it was estimated
      that, in the USA, at most 13% of the annual estrogenic load can be averted by
      fully meeting the contraceptive needs of the population. Therefore, while the
      issue of estrogen impacts on the environment cannot be addressed solely by
      meeting the population's contraceptive needs, a significant fraction of the
      estrogenic mass released to environment can be averted by improving the level
      with which their contraceptive needs are met. 

PMID- 24670975
TI  - Surface reconstruction and chemical evolution of stoichiometric layered cathode
      materials for lithium-ion batteries.
AB  - The present study sheds light on the long-standing challenges associated with
      high-voltage operation of LiNi(x)Mn(x)Co(1-2x)O2 cathode materials for lithium
      ion batteries. Using correlated ensemble-averaged high-throughput X-ray
      absorption spectroscopy and spatially resolved electron microscopy and
      spectroscopy, here we report structural reconstruction (formation of a surface
      reduced layer, to transition) and chemical evolution (formation of a surface
      reaction layer) at the surface of LiNi(x)Mn(x)Co(1-2x)O2 particles. These are
      primarily responsible for the prevailing capacity fading and impedance buildup
      under high-voltage cycling conditions, as well as the first-cycle coulombic
      inefficiency. It was found that the surface reconstruction exhibits a strong
      anisotropic characteristic, which predominantly occurs along lithium diffusion
      channels. Furthermore, the surface reaction layer is composed of lithium fluoride
      embedded in a complex organic matrix. This work sets a refined example for the
      study of surface reconstruction and chemical evolution in battery materials using
      combined diagnostic tools at complementary length scales.

PMID- 24670976
TI  - Renal failure in lithium-treated bipolar disorder: a retrospective cohort study.
AB  - OBJECTIVE: Lithium users are offered routine renal monitoring but few studies
      have quantified the risk to renal health. The aim of this study was to assess the
      association between use of lithium carbonate and incidence of renal failure in
      patients with bipolar disorder. METHODS: This was a retrospective cohort study
      using the General Practice Research Database (GPRD) and a nested validation study
      of lithium exposure and renal failure. A cohort of 6360 participants aged over 18
      years had a first recorded diagnosis of bipolar disorder between January 1, 1990
      and December 31, 2007. Data were examined from electronic primary care records
      from 418 general practices across the UK. The primary outcome was the hazard
      ratio for renal failure in participants exposed to lithium carbonate as compared
      with non-users of lithium, adjusting for age, gender, co-morbidities, and poly
      pharmacy. RESULTS: Ever use of lithium was associated with a hazard ratio for
      renal failure of 2.5 (95% confidence interval 1.6 to 4.0) adjusted for known
      renal risk factors. Absolute risk was age dependent, with patients of 50 years or
      older at particular risk of renal failure: Number Needed to Harm (NNH) was 44 (21
      to 150). CONCLUSIONS: Lithium is associated with an increased risk of renal
      failure, particularly among the older age group. The absolute risk of renal
      failure associated with lithium use remains small.

PMID- 24670977
TI  - The impact of movements and animal density on continental scale cattle disease
      outbreaks in the United States.
AB  - Globalization has increased the potential for the introduction and spread of
      novel pathogens over large spatial scales necessitating continental-scale disease
      models to guide emergency preparedness. Livestock disease spread models, such as
      those for the 2001 foot-and-mouth disease (FMD) epidemic in the United Kingdom,
      represent some of the best case studies of large-scale disease spread. However,
      generalization of these models to explore disease outcomes in other systems, such
      as the United States's cattle industry, has been hampered by differences in
      system size and complexity and the absence of suitable livestock movement data.
      Here, a unique database of US cattle shipments allows estimation of synthetic
      movement networks that inform a near-continental scale disease model of a
      potential FMD-like (i.e., rapidly spreading) epidemic in US cattle. The largest
      epidemics may affect over one-third of the US and 120,000 cattle premises, but
      cattle movement restrictions from infected counties, as opposed to national
      movement moratoriums, are found to effectively contain outbreaks. Slow detection
      or weak compliance may necessitate more severe state-level bans for similar
      control. Such results highlight the role of large-scale disease models in
      emergency preparedness, particularly for systems lacking comprehensive movement
      and outbreak data, and the need to rapidly implement multi-scale contingency
      plans during a potential US outbreak. 

PMID- 24670978
TI  - Black tattoos entail substantial uptake of genotoxicpolycyclic aromatic
      hydrocarbons (PAH) in human skin and regional lymph nodes.
AB  - Hundreds of millions of people worldwide have tattoos, which predominantly
      contain black inks consisting of soot products like Carbon Black or polycyclic
      aromatic hydrocarbons (PAH). We recently found up to 200 MUg/g of PAH in
      commercial black inks. After skin tattooing, a substantial part of the ink and
      PAH should be transported to other anatomical sites like the regional lymph
      nodes. To allow a first estimation of health risk, we aimed to extract and
      quantify the amount of PAH in black tattooed skin and the regional lymph nodes of
      pre-existing tattoos. Firstly, we established an extraction method by using HPLC
      DAD technology that enables the quantification of PAH concentrations in human
      tissue. After that, 16 specimens of human tattooed skin and corresponding
      regional lymph nodes were included in the study. All skin specimen and lymph
      nodes appeared deep black. The specimens were digested and tested for 20
      different PAH at the same time.PAH were found in twelve of the 16 tattooed skin
      specimens and in eleven regional lymph nodes. The PAH concentration ranged from
      0.1-0.6 MUg/cm2 in the tattooed skin and 0.1-11.8 MUg/g in the lymph nodes. Two
      major conclusions can be drawn from the present results. Firstly, PAH in black
      inks stay partially in skin or can be found in the regional lymph nodes.
      Secondly, the major part of tattooed PAH had disappeared from skin or might be
      found in other organs than skin and lymph nodes. Thus, beside inhalation and
      ingestion, tattooing has proven to be an additional, direct and effective route
      of PAH uptake into the human body.

PMID- 24670979
TI  - Intensity and duration of negative emotions: comparing the role of appraisals and
      regulation strategies.
AB  - Intensity and duration are two central characteristics of an emotional response.
      Appraisals and regulation strategies are among the most important determinants of
      these emotion features. However, as intensity and duration are only moderately
      correlated, appraisals and regulation strategies may be differently related to
      these characteristics. A systematic empirical study comparing predictors of
      emotion intensity and duration is missing. The goal of the present study is to
      fill this gap. Participants were asked to recall recently experienced episodes of
      anger, fear, disgust, guilt, sadness, and shame. Subsequently, they were asked to
      answer a number of questions regarding (a) the intensity and duration of these
      emotions, (b) their appraisal of the emotion-eliciting event, and (c) their use
      of a wide range of regulation strategies. Emotion intensity was found to be
      mainly predicted by appraisals whereas emotion duration was equally well
      predicted by appraisals and regulation strategies. 

PMID- 24670980
TI  - Nano-hard template synthesis of pure mesoporous NiO and its application for
      streptavidin protein immobilization.
AB  - A simple and efficient immobilization of streptavidin protein (with hexa
      histidine tag) onto the surface of mesoporous NiO is described. Before
      immobilization of streptavidin protein (with hexa-histidine tag) onto the surface
      of mesoporous NiO, we first synthesized well-organized mesoporous NiO by a
      nanocasting method using mesoporous silica SBA-15 as the hard template. Then, the
      well-organized mesoporous NiO particles were characterized by small angle x-ray
      diffraction (XRD), wide angle XRD, nitrogen adsorption/desorption, and
      transmission electron microscopy (TEM). TEM and small angle XRD suggested the
      formation of mesoporous NiO materials, whereas the wide angle XRD pattern of
      mesoporous NiO indicated that the nickel precursor had been transformed into
      crystalline NiO. The N2 sorption experiments demonstrated that the mesoporous NiO
      particles had a high surface area of 281 m2 g(-1), a pore volume of 0.51 cm3 g(
      1) and a pore size of 4.8 nm. Next, the immobilization of streptavidin protein
      (with hexa-histidine tag) onto the surface of mesoporous NiO was studied.
      Detailed analysis using gel electrophoresis confirmed that this approach can
      efficiently bind his-tagged streptavidin onto the surface of mesoporous NiO
      material since the mesoporous NiO provides sufficient surface sites for the
      binding of streptavidin via non-covalent ligand binding with the histidine tag.

PMID- 24670981
TI  - Pan-tropical analysis of climate effects on seasonal tree growth.
AB  - Climate models predict a range of changes in tropical forest regions, including
      increased average temperatures, decreased total precipitation, reduced soil
      moisture and alterations in seasonal climate variations. These changes are
      directly related to the increase in anthropogenic greenhouse gas concentrations,
      primarily CO2. Assessing seasonal forest growth responses to climate is of utmost
      importance because woody tissues, produced by photosynthesis from atmospheric
      CO2, water and light, constitute the main component of carbon sequestration in
      the forest ecosystem. In this paper, we combine intra-annual tree growth
      measurements from published tree growth data and the corresponding monthly
      climate data for 25 pan-tropical forest sites. This meta-analysis is designed to
      find the shared climate drivers of tree growth and their relative importance
      across pan-tropical forests in order to improve carbon uptake models in a global
      change context. Tree growth reveals significant intra-annual seasonality at
      seasonally dry sites or in wet tropical forests. Of the overall variation in tree
      growth, 28.7% was explained by the site effect, i.e. the tree growth average per
      site. The best predictive model included four climate variables: precipitation,
      solar radiation (estimated with extrasolar radiation reaching the atmosphere),
      temperature amplitude and relative soil water content. This model explained more
      than 50% of the tree growth variations across tropical forests. Precipitation and
      solar radiation are the main seasonal drivers of tree growth, causing 19.8% and
      16.3% of the tree growth variations. Both have a significant positive association
      with tree growth. These findings suggest that forest productivity due to tropical
      tree growth will be reduced in the future if climate extremes, such as droughts,
      become more frequent. 

PMID- 24670983
TI  - Detection and management of perioperative myocardial ischemia.
AB  - PURPOSE OF REVIEW: To review the current evidence for detection and management of
      perioperative myocardial ischemia. RECENT FINDINGS: Patients who sustain a
      myocardial injury after noncardiac surgery are predominantly asymptomatic.
      Myocardial injury after noncardiac surgery is associated with both short-term and
      long-term mortality. Mortality from both cardiac and noncardiac causes is
      significant. SUMMARY: Perioperative physicians should refrain from the use of
      nonsurgical diagnostic criteria for myocardial infarction and adopt the clinical
      entity known as myocardial injury after noncardiac surgery in order to allow for
      better determination of the prevalence of this perioperative complication.
      Studies should focus on establishing the feasibility of broad postoperative
      troponin surveillance following noncardiac surgery. Clinical trials of potential
      therapies for myocardial injury after noncardiac surgery are urgently needed.

PMID- 24670984
TI  - First long-term behavioral records from Cuvier's beaked whales (Ziphius
      cavirostris) reveal record-breaking dives.
AB  - Cuvier's beaked whales (Ziphius cavirostris) are known as extreme divers, though
      behavioral data from this difficult-to-study species have been limited. They are
      also the species most often stranded in association with Mid-Frequency Active
      (MFA) sonar use, a relationship that remains poorly understood. We used satellite
      linked tags to record the diving behavior and locations of eight Ziphius off the
      Southern California coast for periods up to three months. The effort resulted in
      3732 hr of dive data with associated regional movements--the first dataset of its
      kind for any beaked whale--and included dives to 2992 m depth and lasting 137.5
      min, both new mammalian dive records. Deep dives had a group mean depth of 1401 m
      (s.d. = 137.8, n = 1142) and duration of 67.4 min (s.d. = 6.9). The group mean
      time between deep dives was 102.3 min (s.d. = 30.8, n = 783). While the
      previously described stereotypic pattern of deep and shallow dives was apparent,
      there was considerable inter- and intra-individual variability in most
      parameters. There was significant diel behavioral variation, including increased
      time near the surface and decreased shallow diving at night. However, maximum
      depth and the proportion of time spent on deep dives (presumed foraging), varied
      little from day to night. Surprisingly, tagged whales were present within an MFA
      sonar training range for 38% of days locations were received, and though
      comprehensive records of sonar use during tag deployments were not available, we
      discuss the effects frequent acoustic disturbance may have had on the observed
      behaviors. These data better characterize the true behavioral range of this
      species, and suggest caution should be exercised when drawing conclusions about
      behavior using short-term datasets.

PMID- 24670982
TI  - Ecto-5'-nucleotidase (CD73) regulates host inflammatory responses and exacerbates
      murine salmonellosis.
AB  - Food-borne Salmonella spp., are a major cause of hospitalization and death.
      Adenosine, an important immune regulator of inflammation, limits tissue damage
      during infection. CD39 (nucleoside triphosphate dephosphorylase) combined with
      ecto-5'-nucleotidase (CD73) metabolizes ATP to adenosine. We studied the
      expressions of CD39 and CD73 in tissues, and T helper cells in mice after
      Salmonella infection and evaluated the role of CD73 in regulating immune
      responses and bacterial clearance in wild-type and CD73-deficient (CD73(-/-))
      mice. Both CD39 and CD73 transcript levels declined in the infected wild-type
      mice. Compared to wild-type mice, tissues from infected CD73(-/-) mice had
      significantly higher expression of pro-inflammatory cytokines and reduced anti
      inflammatory responses. CD73(-/-) mice were more resistant to infection and had a
      greater inflammatory responses and a significantly lower bacterial load in the
      liver compared to wild-type mice. Thus, CD73 expression attenuates inflammation
      during murine Salmonellosis and impairs immunity, leading to increased bacterial
      colonization and prolonged infection. 

PMID- 24670985
TI  - Coastal nurseries and their importance for conservation of sea kraits.
AB  - Destruction and pollution of coral reefs threaten these marine biodiversity hot
      stops which shelter more than two thirds of sea snake species. Notably, in many
      coral reef ecosystems of the Western Pacific Ocean, large populations of sea
      kraits (amphibious sea snakes) have drastically declined during the past three
      decades. Protecting remaining healthy populations is thus essential. In New
      Caledonia, coral reefs shelter numerous sea krait colonies spread throughout an
      immense lagoon (24,000 km2). Sea kraits feed on coral fish but lay their eggs on
      land. However, ecological information on reproduction and juveniles is extremely
      fragmentary, precluding protection of key habitats for reproduction. Our 10 years
      mark recapture study on Yellow sea kraits (L. saintgironsi >8,700 individuals
      marked) revealed that most neonates aggregate in highly localized coastal sites,
      where they feed and grow during several months before dispersal. Hundreds of
      females emigrate seasonally from remote populations (>50 km away) to lay their
      eggs in these coastal nurseries, and then return home. Protecting these nurseries
      is a priority to maintain recruitment rate, and to retain sea krait populations
      in the future. 

PMID- 24670987
TI  - Sustaining supply of senior academic leadership skills in a shortage environment:
      a short review of a decade of dental experience.
AB  - For the past decade, and expected for the next decade, Australia faces a
      significant health workforce shortage and an acute maldistribution of health
      workforce. Against this background the governments at both national and state
      level have been increasing the training places for all health practitioners and
      trying to redress the imbalance through a strong regional focus on these
      developments. Dentistry has been an active participant in these workforce
      initiatives. This study examines the increasing demand for academics and
      discusses the existing pathways for increase, and also examines in detail the
      advantages of a sustainable, shared-model approach, using dentistry as a model
      for other disciplines. Three non-exclusive pathways for reform are considered:
      importation of academics, delayed retirement and the shared resource approach. Of
      the various solutions outlined in this review a detailed explanation of a cost
      effective shared model of senior academic leadership is highlighted as a viable,
      sustainable model for ameliorating the shortage. 

PMID- 24670986
TI  - Combating non-Hodgkin lymphoma by targeting both CD20 and HLA-DR through CD20-243
      CrossMab.
AB  - Although rituximab has revolutionized the treatment of hematological
      malignancies, the acquired resistance is one of the prime obstacles for cancer
      treatment, and development of novel CD20-targeting antibodies with potent anti
      tumor activities and specificities is urgently needed. Emerging evidence has
      indicated that lysosomes can be considered as an "Achilles heel" for cancer
      cells, and might serve as an effective way to kill resistant cancer cells. HLA-DR
      antibody L243 has been recently reported to elicit potent lysosome-mediated cell
      death in lymphoma and leukemia cells, suggesting that HLA-DR could be used as a
      potential target against lymphoma. In this study, we generated a bispecific
      immunoglobulin G-like antibody targeting both CD20 and HLA-DR (CD20-243 CrossMab)
      through CrossMab technology. We found that the CrossMab could induce remarkably
      high levels of complement-dependent cytotoxicity, antibody-dependent cell
      mediated cytotoxicity and anti-proliferative activity. Notably, although HLA-DR
      is expressed on normal and malignant cells, the CrossMab exhibited highly anti
      tumor specificity, showing efficient eradication of hematological malignancies
      both in vitro and in vivo. Our data indicated that combined targeting of CD20 and
      HLA-DR could be an effective approach against malignancies, suggesting that CD20
      243 CrossMab would be a promising therapeutic agent against lymphoma. 

PMID- 24670988
TI  - Dynamics of the liver stiffness value using transient elastography during the
      perioperative period in patients with valvular heart disease.
AB  - BACKGROUND/AIMS: Liver congestion due to heart failure in patients with valvular
      heart disease (VHD) can result in an overestimate of the liver stiffness (LS) as
      assessed by transient elastography (TE). This prospective pilot study
      investigated the dynamics of LS during the perioperative valve operation period.
      METHODS: Thirty-two patients who underwent a valve operation (case) and 12 who
      underwent a varicose vein operation (control) were prospectively enrolled. LS and
      cardiologic parameters at three time points [baseline, post-operative day (POD)7,
      and POD90] were collected. RESULTS: LS at three time points were consistently
      higher in the case group than those in the control group, although all
      participants did not show evidence of underlying chronic liver disease (all
      P<0.05). In the case group, LS at POD7 increased slightly from the LS at baseline
      (median 7.9->8.4 kPa, P = 0.816), whereas LS at POD90 decreased significantly
      from the LS at POD7 (median 8.4->6.0 kPa; P = 0.026). LS was significantly
      correlated with N-terminal-pro brain natriuretic peptide (NT-proBNP) (rho =
      0.412), left ventricular ejection fraction (rho = -0.494), and central venous
      pressure during the operation (rho = 0.555) at baseline (all P<0.05). LS was
      significantly correlated with NT-proBNP (rho = 0.526) and right ventricular
      pressure (rho = 0.572) at POD7, whereas LS was significantly correlated with NT
      proBNP (rho = 0.590) at POD90 (all P<0.05). CONCLUSIONS: LS can be overestimated
      in patients with VHD due to hepatic congestion. However, LS can be dynamically
      reversed during the perioperative period reflecting the restoration of cardiac
      function after a successful operation.

PMID- 24670989
TI  - Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin-
      or NMDA-dependent mechanism?
AB  - Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for
      brain functioning. Since the demonstration that plasmin is able to process pro
      BDNF to mature BDNF and that these two forms have opposite effects on neuronal
      survival and plasticity, a particular attention has been paid to the link between
      tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t
      PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is
      also considered as a neuromodulator of glutamatergic transmission. In this
      context, the aim of our study was to investigate the effect of recombinant (r)t
      PA administration on brain BDNF metabolism in rats. In the hippocampus, we found
      that rt-PA (10 mg/kg) administration induced a progressive increase in mature
      BDNF levels associated with TrkB activation. In order to delineate the
      mechanistic involved, plasmin activity was assessed and its inhibition was
      attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA receptors were
      antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with rt-PA
      treatment. Our results showed that despite a rise in rt-PA activity, rt-PA
      administration failed to increase hippocampal plasmin activity suggesting that
      the plasminogen/plasmin system is not involved whereas MK801 abrogated the
      augmentation in mature BDNF levels observed after rt-PA administration. All
      together, our results show that rt-PA administration induces increase in
      hippocampal mature BDNF expression and suggests that rt-PA contributes to the
      control of brain BDNF synthesis through a plasmin-independent potentiation of
      NMDA receptors signaling. 

PMID- 24670990
TI  - Conversion of a Rhizopus chinensis lipase into an esterase by lid swapping.
AB  - In an effort to explore the feasibility of converting a lipase into an esterase
      by modifying the lid region, we designed and characterized two novel Rhizopus
      chinensis lipase variants by lid swapping. The substrate specificity of an R.
      chinensis lipase was successfully modified toward water-soluble substrates, that
      is, turned into an esterase, by replacing the hydrophobic lid with a hydrophilic
      lid from ferulic acid esterase from Aspergillus niger Meanwhile, as a comparison,
      the lid of R. chinensis lipase was replaced by a hydrophobic lid from Rhizomucor
      miehei lipase, which did not alter its substrate specificity but led to a 5.4
      fold higher catalytic efficiency (k*cat/K*m) toward p-nitrophenyl laurate. Based
      on the analysis of structure-function relationships, it suggests that the
      amphipathic nature of the lid is very important for the substrate specificity.
      This study provides new insight into the structural basis of lipase specificities
      and a way to tune the substrate preference of lipases.

PMID- 24670991
TI  - Emerging pathways in the regulation of whole body cholesterol flux: therapeutic
      opportunities to target atherosclerosis?

PMID- 24670992
TI  - Pharmacokinetic changes induced by focused ultrasound in glioma-bearing rats as
      measured by dynamic contrast-enhanced MRI.
AB  - Focused ultrasound (FUS) combined with microbubbles has been shown to be a
      noninvasive and targeted drug delivery technique for brain tumor treatment. The
      purpose of this study was to measure the kinetics of Gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA) in glioma-bearing rats in the
      presence of FUS-induced blood-brain barrier disruption (BBB-D) by magnetic
      resonance imaging (MRI). A total of ten glioma-bearing rats (9-12 weeks, 290-340
      g) were used in this study. Using dynamic contrast-enhanced (DCE)-MRI, the
      spatial permeability of FUS-induced BBB-D was evaluated and the kinetic
      parameters were calculated by a general kinetic model (GKM). The results
      demonstrate that the mean Ktrans of the sonicated tumor (0.128+/-0.019 at 20 min
      and 0.103+/-0.023 at 24 h after sonication, respectively) was significantly
      higher than (2.46-fold at 20 min and 1.78-fold at 24 h) that of the contralateral
      (non-sonicated) tumor (0.052+/-0.019 at 20 min and 0.058+/-0.012 at 24 h after
      sonication, respectively). In addition, the transfer constant Ktrans in the
      sonicated tumor correlated strongly with tissue EB extravasation (R = 0.95),
      which suggests that DCE-MRI may reflect drug accumulation in the brain.
      Histological observations showed no macroscopic damage except for a few small
      erythrocyte extravasations. The current study demonstrates that DCE-MRI can
      monitor the dynamics of the FUS-induced BBB-D process and constitutes a useful
      tool for quantifying BBB permeability in tumors. 

PMID- 24670993
TI  - Streptococcus suis type 2 SSU0587 protein is a beta-galactosidase that
      contributes to bacterial adhesion but not to virulence in mice.
AB  - Bacterial surface proteins play key roles in virulence and often contribute to
      bacterial adhesion and invasion. We discovered that the Streptococcus suis type 2
      (SS2) gene SSU0587 encodes a protein of 1,491 amino acids that possesses beta
      galactosidase activity. The surface association of the protein was dependent upon
      sortase activity. Deleting SSU0587 from clinical SS2 isolate JX081101 caused a
      loss of both beta-galactosidase activity and adherence to microvascular
      endothelial cells. Deleting SSU0587 had no measurable impact on either invasion
      of microvascular endothelial cells or on virulence in a murine infection model,
      although the concentration of JX081101DeltaSSU0587 was reduced in the brains of
      infected mice, as compared with the pathogen loads of the wild-type strain. 

PMID- 24670994
TI  - Intranasal administration of plasmid DNA nanoparticles yields successful
      transfection and expression of a reporter protein in rat brain.
AB  - Viral vectors are a commonly used method for gene therapy because of their highly
      efficient transduction of cells. However, many vectors have a small genetic
      capacity, and their potential for immunogenicity can limit their usefulness.
      Moreover, for disorders of the central nervous system (CNS), the need for
      invasive surgical delivery of viruses to the brain also detracts from their
      clinical applicability. Here, we show that intranasal delivery of unimolecularly
      compacted DNA nanoparticles (DNA NPs), which consist of single molecules of
      plasmid DNA encoding enhanced green fluorescent protein (eGFP) compacted with 10
      kDa polyethylene glycol (PEG)-substituted lysine 30-mers (CK30PEG10k),
      successfully transfect cells in the rat brain. Direct eGFP fluorescence
      microscopy, eGFP-immunohistochemistry (IHC) and eGFP-ELISA all demonstrated eGFP
      protein expression 2 days after intranasal delivery. eGFP-positive cells were
      found throughout the rostral-caudal axis of the brain, most often adjacent to
      capillary endothelial cells. This localization provides evidence for distribution
      of the nasally administered DNA NPs via perivascular flow. These results are the
      first report that intranasal delivery of DNA NPs can bypass the blood-brain
      barrier and transfect and express the encoded protein in the rat brain, affording
      a non-invasive approach for gene therapy of CNS disorders.

PMID- 24670996
TI  - TALEN-mediated editing of endogenous T-cell receptors facilitates efficient
      reprogramming of T lymphocytes by lentiviral gene transfer.
AB  - Adoptive immunotherapy with T lymphocytes expressing transgenic T-cell receptors
      (TCRs) has shown significant clinical efficacy in various malignant diseases.
      However, concurrent expression of endogenous and transgenic TCRs in one and the
      same T cell may impair efficacy and cause safety problems owing to mispairings.
      The most elegant approach to address these issues is the complete shutoff of the
      endogenous receptor chains by genome editing. To this end, we designed TCR-alpha
      and TCR-beta-specific pairs of transcription activator-like effector nucleases
      (TALENs). TALENs were delivered into T cells using an optimized messenger RNA
      electroporation protocol. Based thereon, we obtained precise and highly efficient
      knockout (KO) in Jurkat (TCR-alpha: 59.7 +/- 4.0%, TCR-beta: 37.4 +/- 7.3%) as
      well as primary T cells (TCR-alpha: 58.0 +/- 15.0%, TCR-beta: 41.0 +/- 17.6%).
      Moreover, a successive KO strategy for the endogenous TCR chains combined with
      subsequent transduction of the respective chains of an Influenza virus-specific
      model TCR led to complete reprogramming of T cells with strongly improved
      expression and functionality of transgenic TCRs. In conclusion, we have developed
      novel means for the efficient genome editing in primary T lymphocytes.

PMID- 24670995
TI  - AAV-mediated expression of human PRELP inhibits complement activation, choroidal
      neovascularization and deposition of membrane attack complex in mice.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness among
      the elderly. Approximately 50% of AMD patients have a polymorphism in the
      negative regulator of complement known as Factor H. Individuals homozygous for a
      Y402H polymorphism in Factor H have elevated levels of membrane attack complex
      (MAC) in their choroid and retinal pigment epithelium relative to individuals
      homozygous for the wild-type allele. An inability to form MAC due to a
      polymorphism in C9 is protective against the formation of choroidal
      neovascularization (CNV) in AMD patients. Hence, blocking MAC in AMD patients may
      be protective against CNV. Here we investigate the potential of human
      proline/arginine-rich end leucine-rich repeat protein (PRELP) as an inhibitor of
      complement-mediated damage when delivered via the subretinal route using an
      AAV2/8 vector. In a fluorescence-activated cell sorting (FACS) lysis assay, PRELP
      inhibited normal human serum-mediated lysis of Hepa-1c1c7 cells by 18.7%.
      Unexpectedly, PRELP enhanced the formation of tubes by human umbilical vein
      endothelial cells (HUVECs) by approximately 240%, but, when delivered via an AAV
      vector to the retina of mice, PRELP inhibited laser-induced CNV by 60%. PRELP
      reduced deposition of MAC in vivo by 25.5%. Our results have implications for the
      development of complement inhibitors as a therapy for AMD.

PMID- 24670997
TI  - Mammals of Australia's tropical savannas: a conceptual model of assemblage
      structure and regulatory factors in the Kimberley region.
AB  - We construct a state-and-transition model for mammals in tropical savannas in
      northern Australia to synthesize ecological knowledge and understand mammalian
      declines. We aimed to validate the existence of alternative mammal assemblage
      states similar to those in arid Australian grasslands, and to speculate on
      transition triggers. Based on the arid grassland model, we hypothesized that
      assemblages are partitioned across rainfall gradients and between substrates. We
      also predicted that assemblages typical of arid regions in boom periods would be
      prevalent in savannas with higher and more regular rainfall. Data from eight
      mammal surveys from the Kimberley region, Western Australia (1994 to 2011) were
      collated. Survey sites were partitioned across rainfall zones and habitats. Data
      allowed us to identify three assemblage states: State 0:--low numbers of mammals,
      State II:--dominated by omnivorous rodents and State III:--dominated by rodents
      and larger marsupials. Unlike arid grasslands, assemblage dominance by
      insectivorous dasyurids (State I) did not occur in savannas. Mammal assemblages
      were partitioned across rainfall zones and between substrates as predicted, but
      unlike arid regions-were not related strongly to yearly rainfall. Mammal
      assemblage composition showed high regional stability, probably related to high
      annual rainfall and predictable wet season resource pulses. As a consequence, we
      speculate that perpetually booming assemblages in savannas allow top-down control
      of the ecosystem, with suppression of introduced cats by the dingo, the region's
      top predator. Under conditions of low or erratic productivity, imposed
      increasingly by intense fire regimes and introduced herbivore grazing, dingoes
      may not limit impacts of cats on native mammals. These interacting factors may
      explain contemporary declines of savanna mammals as well as historical declines
      in arid Australia. The cat-ecosystem productivity hypothesis raised here differs
      from the already-articulated cat-habitat structure hypothesis for mammal
      declines, and we suggest approaches for explicit testing of transition triggers
      for competing hypotheses.

PMID- 24670998
TI  - Retinal nerve fiber layer thickness modification after internal limiting membrane
      peeling.
AB  - PURPOSE: To identify early and late retinal nerve fiber layer thickness (RNFLT)
      modification after internal limiting membrane peeling for idiopathic macular hole
      or epiretinal membrane and to correlate RNFLT to visual field indices. METHODS:
      Single-center, prospective, interventional consecutive case series. Complete
      ophthalmic examination, fundus images, and spectral domain optical coherence
      tomography were performed in 30 eyes of 30 patients before and 1, 3, and 6 months
      after surgery. Six peripapillary sectors (superotemporal, temporal,
      inferotemporal, inferonasal, nasal, superonasal) and global RNFLT were evaluated.
      Visual field was performed preoperatively and 6 months postoperatively. RESULTS:
      Significant RNFLT modification was found after surgery (P < 0.0001).
      Specifically, RNFLT significantly increased in all, but the temporal sectors, 1
      month after surgery, and it returned to preoperative values at the third month.
      Six months after surgery, RNFLT was lower than basal values in the
      superotemporal, inferotemporal, and temporal sectors (P < 0.001, P < 0.05, and P
      < 0.001, respectively) with an average reduction of 18.2 +/- 9.8 um. No
      correlation was found between RNFLT and the visual field indices. CONCLUSION: The
      diffuse RNFLT increase 1 month postoperatively could be because of inflammatory
      responses. The reduction of RNFLT in the temporal sectors 6 months
      postoperatively could indicate damage to the macular retinal nerve fiber layer
      caused by internal limiting membrane peeling.

PMID- 24670999
TI  - Critical evaluation of the usability of augmented reality ophthalmoscopy for the
      training of inexperienced examiners.
AB  - PURPOSE: To measure the value of augmented reality technology usage to teach the
      medical students performing binocular indirect ophthalmoscopy. METHODS: Thirty
      seven medical students were randomly assigned to the training of binocular
      indirect ophthalmoscopy either in the conventional way or with augmented reality
      ophthalmoscopy (ARO). For testing student's skills, they had to examine a real
      person using a conventional ophthalmoscopy system and draw the optic disk. They
      also had to fill out a questionnaire. Subjective and objective evaluations were
      performed. RESULTS: Thirty-seven students were randomly assigned to two groups.
      Eighteen students were trained with conventional ophthalmoscopy and 19 students
      with ARO. The questionnaires showed no differences. Performing an objective
      analysis, the median ophthalmoscopy training score for the conventional
      ophthalmoscopy group was 1.2 (range, 0.67-2) and showed a significant difference
      (P < 0.0033) to the ARO group (median 2; range, 0.67-2). CONCLUSION: The study
      provides evidence that a single ARO training is efficient to improve
      ophthalmoscopy skills. As the objective analysis showed, the ARO group had a
      significantly superior performance. Our study also indicates that subjective
      evaluation of the fundus drawings without systematic analysis is prone to errors.

PMID- 24671000
TI  - Women's risk of repeat abortions is strongly associated with alcohol consumption:
      a longitudinal analysis of a Russian national panel study, 1994-2009.
AB  - Abortion rates in Russia, particularly repeat abortions, are among the highest in
      the world, and abortion complications make a substantial contribution to the
      country's high maternal mortality rate. Russia also has a very high rate of
      hazardous alcohol use. However, the association between alcohol use and abortion
      in Russia remains unexplored. We investigated the longitudinal predictors of
      first and repeat abortion, focussing on women's alcohol use as a risk factor.
      Follow-up data from 2,623 women of reproductive age (16-44 years) was extracted
      from 14 waves of the Russian Longitudinal Monitoring Survey (RLMS), a nationally
      representative panel study covering the period 1994-2009. We used discrete time
      hazard models to estimate the probability of having a first and repeat abortion
      by social, demographic and health characteristics at the preceding study wave.
      Having a first abortion was associated with demographic factors such as age and
      parity, whereas repeat abortions were associated with low education and alcohol
      use. After adjustment for demographic and socioeconomic factors, the risk of
      having a repeat abortion increased significantly as women's drinking frequency
      increased (P<0.001), and binge drinking women were significantly more likely to
      have a repeat abortion than non-drinkers (OR 2.28, 95% CI 1.62-3.20). This
      association was not accounted for by contraceptive use or a higher risk of
      pregnancy. Therefore the determinants of first and repeat abortion in Russia
      between 1994-2009 were different. Women who had repeat abortions were
      distinguished by their heavier and more frequent alcohol use. The mechanism for
      the association is not well understood but could be explained by unmeasured
      personality factors, such as risk taking, or social non-conformity increasing the
      risk of unplanned pregnancy. Heavy or frequent drinkers constitute a particularly
      high risk group for repeat abortion, who could be targeted in prevention efforts.

PMID- 24671001
TI  - A novel human anti-interleukin-1beta neutralizing monoclonal antibody showing in
      vivo efficacy.
AB  - The pro-inflammatory cytokine interleukin (IL)-1beta is a clinical target in many
      conditions involving dysregulation of the immune system; therapeutics that block
      IL-1beta have been approved to treat diseases such as rheumatoid arthritis (RA),
      neonatal onset multisystem inflammatory diseases, cryopyrin-associated periodic
      syndromes, active systemic juvenile idiopathic arthritis. Here, we report the
      generation and engineering of a new fully human antibody that binds tightly to IL
      1beta with a neutralization potency more than 10 times higher than that of the
      marketed antibody canakinumab. After affinity maturation, the derived antibody
      shows a>30-fold increased affinity to human IL-1beta compared with its parent
      antibody. This anti-human IL-1beta IgG also cross-reacts with mouse and monkey IL
      1beta, hence facilitating preclinical development. In a number of mouse models,
      this antibody efficiently reduced or abolished signs of disease associated with
      IL-1beta pathology. Due to its high affinity for the cytokine and its potency
      both in vitro and in vivo, we propose that this novel fully human anti-IL-1beta
      monoclonal antibody is a promising therapeutic candidate and a potential
      alternative to the current therapeutic arsenal. 

PMID- 24671002
TI  - High plasma levels of islet amyloid polypeptide in young with new-onset of type 1
      diabetes mellitus.
AB  - AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) is a beta cell hormone secreted
      together with insulin upon glucose stimulation. IAPP participates in normal
      glucose regulation, but IAPP is also known for its ability to misfold and form
      islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and
      deposited amyloid disrupts normal islet architecture. Even though IAPP and
      amyloid formation are much discussed in type 2 diabetes, our aim was to study the
      significance of IAPP in type 1 diabetes. RESULTS: Plasma IAPP levels in children
      and adolescents with newly diagnosed type 1 diabetes (n = 224) were analysed and
      concentrations exceeding 100 pmol/L (127.2-888.7 pmol/L) were found in 11%
      (25/224). The IAPP increase did not correlate with C-peptide levels.
      CONCLUSIONS/INTERPRETATION: Plasma levels of IAPP and insulin deviate in a
      subpopulation of young with newly-diagnosed type 1 diabetes. The determined
      elevated levels of IAPP might increase the risk for IAPP misfolding and formation
      of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the
      list over putative pathological factors causing type 1 diabetes.

PMID- 24671004
TI  - Hypertriglyceridemic Pancreatitis Caused by the Oral Contraceptive Agent
      Estrostep.
AB  - Norethindrone acetate/ethinyl estradiol (Estrostep; Warner Chilcott, Rockaway,
      New Jersey) is an "estrophasic" type of oral contraceptive, which combines a
      continuous low progestin dose with a gradually increasing estrogen dose. In
      clinical trials, this medication failed to produce clinically significant changes
      in serum lipid levels. We report a case of severe hypertriglyceridemia-induced
      acute pancreatitis in a 24-year-old woman caused by Estrostep, occurring nearly
      10 years after she began using the drug. The patient was admitted to the medical
      intensive care unit (ICU) for aggressive volume resuscitation and management of
      severe electrolyte abnormalities. Laboratory studies obtained on admission
      indicated severe hypertriglyceridemia (2,200 mg/dL), hyponatremia (120 mEq/L),
      and hypocalcemia (0.78 mmol/L). Amylase and lipase levels were also elevated (193
      and 200 U/L, respectively). Ranson score calculated after 48 hours of admission
      was 4, and her Acute Physiology and Chronic Health Evaluation (APACHE) IV score
      was 35. Treatment included an insulin infusion, omega-3 fatty acid esters, and
      gemfibrozil. The insulin infusion reduced serum triglyceride levels by 50% after
      1 day of treatment and to 355 mg/dL by day 7 of her ICU course. We believe that
      this is the first reported case of severe, acute hypertriglyceridemia-induced
      pancreatitis caused by this medication. 

PMID- 24671003
TI  - A genome-wide perspective of miRNAome in response to high temperature, salinity
      and drought stresses in Brassica juncea (Czern) L.
AB  - Micro RNAs (miRNAs) are involved in diverse biological processes including
      adaptive response towards abiotic stresses. To unravel small RNAs and more
      specifically miRNAs that can potentially regulate determinants of abiotic stress
      tolerance, next generation sequencing of B. juncea seedlings subjected to high
      temperature, high salt and drought conditions was carried out. With the help of
      UEA sRNA workbench software package, 51 conserved miRNAs belonging to 30 miRNA
      families were identified. As there was limited genomic information available for
      B. juncea, we generated and assembled its genome sequence at a low coverage.
      Using the generated sequence and other publically available Brassica
      genomic/transcriptomic resources as mapping reference, 126 novel (not reported in
      any plant species) were discovered for the first time in B. juncea. Further
      analysis also revealed existence of 32 and 37 star sequences for conserved and
      novel miRNAs, respectively. The expression of selected conserved and novel miRNAs
      under conditions of different abiotic stresses was revalidated through universal
      TaqMan based real time PCR. Putative targets of identified conserved and novel
      miRNAs were predicted in B. rapa to gain insights into functional roles
      manifested by B. juncea miRNAs. Furthermore, SPL2-like, ARF17-like and a NAC
      domain containing protein were experimentally validated as targets of miR156,
      miR160 and miR164 respectively. Investigation of gene ontologies linked with
      targets of known and novel miRNAs forecasted their involvement in various
      biological functions. 

PMID- 24671005
TI  - Disease severity affects obstacle crossing in people with Parkinson's disease.
AB  - The current study evaluated the effects of disease severity on the control of
      obstacle crossing in people with idiopathic Parkinson's disease (PD). Forty-five
      subjects participated in the study, including 15 patients with mild PD
      (classified as stage 1 to 1.5 of the Hoehn and Yahr Rating Scale), 15 patients
      with moderate PD (classified as stage 2 to 3 of the Hoehn and Yahr Rating Scale),
      and 15 neurologically healthy individuals. Groups were matched by sex, age, body
      mass, and body height. The obstacle crossing task required participants to walk
      along a pathway and step over an obstacle (half of the knee height, positioned in
      the middle of the pathway). Patients were tested in a typically medicated state.
      Kinematic data were recorded using an optoelectronic tridimensional system. The
      outcome measures included spatiotemporal measures of obstacle avoidance. There
      were no significant differences between patients with mild PD and healthy
      individuals. Patients with moderate PD exhibited shorter distances for leading
      toe clearance and leading foot placement after the obstacle than did healthy
      individuals. Patients with moderate PD tended to exhibit a lower leading
      horizontal mean velocity during obstacle crossing than did healthy individuals.
      We found significant negative relationships between obstacle crossing measures
      and disease severity (score on the motor section of the Unified Parkinson's
      Disease Rating Scale). These findings suggest that disease severity affects
      locomotor behavior during obstacle crossing in PD. Specifically, obstacle
      avoidance was not affected in the early stages of PD; however, bradykinesia and
      hypometria influenced obstacle crossing in patients with moderate PD. 

PMID- 24671006
TI  - Controlling social stress in virtual reality environments.
AB  - Virtual reality exposure therapy has been proposed as a viable alternative in the
      treatment of anxiety disorders, including social anxiety disorder. Therapists
      could benefit from extensive control of anxiety eliciting stimuli during virtual
      exposure. Two stimuli controls are studied in this study: the social dialogue
      situation, and the dialogue feedback responses (negative or positive) between a
      human and a virtual character. In the first study, 16 participants were exposed
      in three virtual reality scenarios: a neutral virtual world, blind date scenario,
      and job interview scenario. Results showed a significant difference between the
      three virtual scenarios in the level of self-reported anxiety and heart rate. In
      the second study, 24 participants were exposed to a job interview scenario in a
      virtual environment where the ratio between negative and positive dialogue
      feedback responses of a virtual character was systematically varied on-the-fly.
      Results yielded that within a dialogue the more positive dialogue feedback
      resulted in less self-reported anxiety, lower heart rate, and longer answers,
      while more negative dialogue feedback of the virtual character resulted in the
      opposite. The correlations between on the one hand the dialogue stressor ratio
      and on the other hand the means of SUD score, heart rate and audio length in the
      eight dialogue conditions showed a strong relationship: r(6) = 0.91, p = 0.002;
      r(6) = 0.76, p = 0.028 and r(6) = -0.94, p = 0.001 respectively. Furthermore,
      more anticipatory anxiety reported before exposure was found to coincide with
      more self-reported anxiety, and shorter answers during the virtual exposure.
      These results demonstrate that social dialogues in a virtual environment can be
      effectively manipulated for therapeutic purposes. 

PMID- 24671007
TI  - Excess baggage for birds: inappropriate placement of tags on gannets changes
      flight patterns.
AB  - Devices attached to flying birds can hugely enhance our understanding of their
      behavioural ecology for periods when they cannot be observed directly. For this,
      scientists routinely attach units to either birds' backs or their tails. However,
      inappropriate payload distribution is critical in aircraft and, since birds and
      planes are subject to the same laws of physics during flight, we considered
      aircraft aerodynamic constraints to explain flight patterns displayed by northern
      gannets Sula bassana equipped with (small ca. 14 g) tail- and back-mounted
      accelerometers and (larger ca. 30 g) tail-mounted GPS units. Tail-mounted GPS
      fitted birds showed significantly higher cumulative numbers of flap-glide cycles
      and a higher pitch angle of the tail than accelerometer-equipped birds,
      indicating problems with balancing inappropriately placed weights with knock-on
      consequences relating to energy expenditure. These problems can be addressed by
      carefully choosing where to place tags on birds according to the mass of the tags
      and the lifestyle of the subject species. 

PMID- 24671008
TI  - To fix or not to fix? The role of fibular fixation in distal shaft fractures of
      the leg.

PMID- 24671009
TI  - Current status of fibrosis markers.
AB  - PURPOSE OF REVIEW: Improved understanding of the pathophysiology of fibrosis and
      recent technological advances have resulted in the development of several serum
      biomarkers and imaging tools as noninvasive alternatives to biopsy. Most of these
      markers have been developed in chronic hepatitis C (CHC) and nonalcoholic fatty
      liver disease (NAFLD) patients. This review highlights some of the recent
      advances and potential clinical application of these modalities. RECENT FINDINGS:
      Many noninvasive approaches initially developed for binary disease staging in CHC
      continue to be refined for diagnostic use in other chronic liver disease such as
      NAFLD. A combination of serum markers and imaging tools appears useful in
      reducing the need for biopsy for the diagnosis of cirrhosis, and providing
      functional assessment in advanced stage disease. Cytokeratin-18 fragments,
      controlled attenuation parameter (CAP), real-time elastography, and magnetic
      resonance imaging approaches appear promising for NAFLD, but require further
      validation. SUMMARY: Current noninvasive tests of fibrosis provide good
      diagnostic and prognostic utility for advanced stage liver disease, and have been
      adapted into clinical practice for CHC. Reliable biomarkers for steatosis,
      nonalcoholic steatohepatitis, and assessment of fibrosis progression in chronic
      liver disease are still required. Continued advances in bioimaging and functional
      genomics will be important for quantitative assessment of fibrosis and future
      biomarker development.

PMID- 24671010
TI  - Primary biliary cirrhosis in 2014.
AB  - PURPOSE OF REVIEW: Primary biliary cirrhosis (PBC) was first described in the
      1950s as a clinical syndrome of progressive cholestatic liver disease resulting
      from chronic inflammatory destruction of the intrahepatic bile ducts. In the
      1980s, the autoimmune nature of the disease was appreciated with the discovery of
      disease-specific loss of immune tolerance to the pyruvate dehydrogenase complex
      and subsequent development of antimitochondrial antibodies and autoreactive T
      cells. Then, in the 1990s, multiple clinical trials demonstrating the efficacy of
      ursodiol as a treatment for PBC were published, although it has been clear that
      ursodiol is not a cure and only delays progression in some patients. RECENT
      FINDINGS: The study of PBC in the 2000s has been buoyed by two basic science
      advances: rapid sequencing technologies that have led to genome wide association
      studies, and elucidation of the role of nuclear hormone receptors in the
      regulation of bile salt metabolism, which has led to novel therapies under study
      for cholestatic diseases. SUMMARY: Today's clinician should be able to determine
      which patients with PBC are likely to progress despite treatment with ursodiol
      and understand the putative new bile acid and immunosuppressant treatment
      strategies under development, as well as be aware of the recently described
      genetic factors at play in the development of PBC.

PMID- 24671011
TI  - Memory effects in stock price dynamics: evidences of technical trading.
AB  - Technical trading represents a class of investment strategies for Financial
      Markets based on the analysis of trends and recurrent patterns in price time
      series. According standard economical theories these strategies should not be
      used because they cannot be profitable. On the contrary, it is well-known that
      technical traders exist and operate on different time scales. In this paper we
      investigate if technical trading produces detectable signals in price time series
      and if some kind of memory effects are introduced in the price dynamics. In
      particular, we focus on a specific figure called supports and resistances. We
      first develop a criterion to detect the potential values of supports and
      resistances. Then we show that memory effects in the price dynamics are
      associated to these selected values. In fact we show that prices more likely re
      bounce than cross these values. Such an effect is a quantitative evidence of the
      so-called self-fulfilling prophecy, that is the self-reinforcement of agents'
      belief and sentiment about future stock prices' behavior. 

PMID- 24671013
TI  - Serum potassium levels predict blood pressure response to aldosterone antagonists
      in resistant hypertension.
AB  - The objective of this study was to identify factors associated with the blood
      pressure (BP) response to spironolactone--aldosterone receptor antagonist as an
      add-on therapy in patients with resistant hypertension (HTN). We retrospectively
      reviewed the data of subjects with resistant HTN who were treated with add-on
      spironolactone in a large HTN clinic. A paired Student's t-test was used to
      assess the differences between the BP values before and during spironolactone
      administration, and multivariate analysis was used to assess the predictors of a
      satisfactory BP response (a decrease in systolic BP >10%). We analyzed the data
      of 48 hypertensive participants. The add-on spironolactone therapy had a
      significant BP-lowering effect in both systolic and diastolic BP values (P < 0.01
      for both). Baseline serum potassium levels of <4.5 mEq l(-1) were associated with
      a satisfactory BP response (P < 0.01). Furthermore, every decrement of 1 mEq l(
      1) of serum potassium was independently associated with a fivefold higher rate of
      achieving a satisfactory BP response to spironolactone therapy (P = 0.024).
      Additional factors independently associated with an improved systolic BP response
      were old age (P = 0.033), body mass index (P = 0.033) and high baseline systolic
      BP (P=0.004). Our results support the use of add-on spironolactone therapy in
      patients with resistant HTN who are elderly and obese and have high systolic BP
      and serum potassium levels <4.5 mEq l(-1).

PMID- 24671014
TI  - Genetic risk assessment for cardiovascular disease with seven genes associated
      with plasma C-reactive protein concentrations in Asian populations.
AB  - Plasma C-reactive protein (CRP) level is a predictor of cardiovascular risk. We
      performed a meta-analysis on the effect of 12 single-nucleotide polymorphisms
      (SNPs) within 8 candidate loci in 36 752 Asians. In addition, we created weighted
      genetic risk scores (wGRSs) to evaluate the combined effects of genetic variants,
      which were suggested in the meta-analysis, for predicting the risks of elevated
      CRP levels as well as increased risks of hypertension and cardiovascular disease
      (CVD) in 748 Koreans. Nine SNPs located in seven genes, CRP, IL6R, GCKR, IL6,
      CYP17A1, HNF1A and APOE, were significantly associated with circulating CRP
      levels in this meta-analysis. Two SNPs, rs7310409 (HNF1A, P=3.4 * 10(-23)) and
      rs7553007 (CRP, P=3.4 * 10(-17)), had the most significant effects on CRP levels;
      and two SNPs, rs2097677 (IL6) and rs1004467 (CYP17A1) have never been found in
      the previous European meta-analysis. In Koreans, the subjects in the highest wGRS
      group had an ~2.5-fold higher mean CRP level compared with those in the lowest
      wGRS group (P=2.1 * 10(-5)). We observed significant increases in the risks of
      hypertension (odds ratio=2.18, P=0.006) and CVD (odds ratio=9.59, P=3.2 * 10(-6))
      among the subjects in the highest wGRS group. The wGRS models specific to Koreans
      may warrant further validation to be used as a proxy for the risk of CVD in
      Asians. 

PMID- 24671015
TI  - Association between blood pressure and disability-free survival among community
      dwelling elderly patients receiving antihypertensive treatment.
AB  - A reduction of elevated blood pressure (BP) is an important treatment goal in
      elderly hypertensive patients. However, excessive reduction of systolic BP (SBP)
      and/or diastolic BP (DBP) might be harmful in such patients. We investigated
      whether this was the case with regard to risk of incident disability or death in
      community-dwelling elderly subjects. We analyzed 570 patients receiving
      antihypertensive treatment aged 65-94 years. The endpoint was the composite
      outcome of incident disability, defined as first certification of a support/care
      need or death. Relationships among each of the four classes of SBP or DBP and the
      risk of incident disability or death were estimated using the Cox proportional
      hazards model. Over four years, 77 (13.5%) incident disabilities or deaths
      occurred. After adjustment for age, sex and variables selected according to their
      univariate analysis P-value <0.20, the risk of events was significantly higher in
      subjects with baseline SBP<120 mm Hg (hazard ratio (HR)=2.81, P=0.023) and ?160
      mm Hg (HR=4.32, P<0.001), compared with subjects with baseline SBP of 140-159 mm
      Hg, who showed the lowest incidence of events. This J-curve relationship was
      observed in very elderly patients (?75 years) but not in younger patients.
      Patients with SBP<120 mm Hg tended to have a higher risk of incident disability
      caused by cerebral events, and those with SBP?160 mm Hg had a higher risk of
      incident disability caused by falls/bone fractures. These observations indicate
      that excessive BP reduction could cause discontinuance of disability-free
      survival in community-dwelling elderly patients. 

PMID- 24671012
TI  - The macrophage LBP gene is an LXR target that promotes macrophage survival and
      atherosclerosis.
AB  - The liver X receptors (LXRs) are members of the nuclear receptor superfamily that
      regulate sterol metabolism and inflammation. We sought to identify previously
      unknown genes regulated by LXRs in macrophages and to determine their
      contribution to atherogenesis. Here we characterize a novel LXR target gene, the
      lipopolysaccharide binding protein (LBP) gene. Surprisingly, the ability of LXRs
      to control LBP expression is cell-type specific, occurring in macrophages but not
      liver. Treatment of macrophages with oxysterols or loading with modified LDL
      induces LBP in an LXR-dependent manner, suggesting a potential role for LBP in
      the cellular response to cholesterol overload. To investigate this further, we
      performed bone marrow transplant studies. After 18 weeks of Western diet feeding,
      atherosclerotic lesion burden was assessed revealing markedly smaller lesions in
      the LBP(-/-) recipients. Furthermore, loss of bone marrow LBP expression
      increased apoptosis in atherosclerotic lesions as determined by terminal
      deoxynucleotidyl transferase dUTP nick end labeling staining. Supporting in vitro
      studies with isolated macrophages showed that LBP expression does not affect
      cholesterol efflux but promotes the survival of macrophages in the setting of
      cholesterol loading. The LBP gene is a macrophage-specific LXR target that
      promotes foam cell survival and atherogenesis.

PMID- 24671017
TI  - Impact of renin-angiotensin system inhibition on microalbuminuria in type 2
      diabetes: a post hoc analysis of the Shiga Microalbuminuria Reduction Trial
      (SMART).

PMID- 24671016
TI  - Antihypertensive drug classes have different effects on short-term blood pressure
      variability in essential hypertension.
AB  - Increased blood pressure variability (BPV) contributes to end-organ damage,
      cardiovascular events and mortality associated with hypertension. In a cohort of
      2780 hypertensive patients treated by either calcium channel blockers (CCBs),
      diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor
      blockers (ARBs) or beta-blockers alone or in combination, we compared indices of
      short-term BPV according to the different treatments. Short-term BPV was
      calculated as the standard deviation (s.d.) of 24 h, daytime or nighttime
      systolic blood pressure and diastolic blood pressure (SBP and DBP). Short-term
      BPV was compared between patients treated with a given antihypertensive class of
      interest (alone or in combination) and those not treated with this class, after
      controlling for ambulatory average blood pressure, heart rate, age, gender,
      propensity scores and carotid-femoral pulse wave velocity. Patients treated with
      CCBs (n=1247) or diuretics (n=1486) alone, or in addition to other drugs had
      significant lower s.d. of 24-h SBP compared with those not treated with these
      classes (mean differences in s.d. -0.50+/-0.50 mm Hg, P=0.001 and -0.17+/-0.15 mm
      Hg, P=0.05, respectively). There was no significant difference regarding
      treatment with or without ARBs, ACEIs and beta-blockers. The combinations of CCBs
      with diuretics or ARBs on top of other treatments resulted in a lower 24-h SBP
      variability (mean differences in s.d. -0.43+/-0.17 mm Hg, P=0.02 and -0.44+/-0.19
      mm Hg, P=0.005 vs. other combination uses, respectively). Antihypertensive drug
      classes have differential effects on short-term BPV with a greater reduction in
      patients treated with CCBs and diuretics. The combinations of CCBs with diuretics
      may be the most efficient treatments in lowering BPV. 

PMID- 24671018
TI  - Relationship between serum uric acid levels and hypertension among Japanese
      individuals not treated for hyperuricemia and hypertension.
AB  - The cause and effect relationship between serum uric acid levels and hypertension
      can be difficult to evaluate because antihypertensive drugs sometimes affect uric
      acid levels. This cross-sectional study investigated the relationship between
      serum uric acid levels and hypertension in a general, healthy Japanese population
      who were not receiving medication for hyperuricemia or hypertension. We
      retrospectively analyzed the medical records of 90 143 Japanese people (men,
      49.1%; age, 46.3+/-12.0 years) undergoing an annual medical examination at St
      Luke's International Hospital Center for Preventive Medicine, Tokyo, between
      January 2004 and June 2010. Of these individuals, 82 722 (91.8%) who had never
      taken medications for gout, hyperuricemia or hypertension were enrolled. We
      compared the participant characteristics and prevalence of diastolic hypertension
      (?90 mm Hg) and/or systolic hypertension (?140 mm Hg) by serum uric acid
      quartile. The odds ratio (OR) of hypertension was 1.20 for each 1 mg dl(-1)
      increase in serum uric acid level after adjustment for age, sex, body mass index
      (BMI), dyslipidemia, diabetes, smoking and estimated glomerular filtration rate
      (eGFR). Compared with the lowest serum uric acid quartile, participants in the
      highest quartile had a 3.7-fold higher OR for hypertension. After adjustment for
      age, BMI, dyslipidemia, diabetes, smoking and eGFR, these ORs were 1.79 (1.62
      1.98) in the total study population, 1.58 (1.44-1.75) in men and 1.60 (1.39-1.84)
      in women. The results were similar for both systolic and diastolic hypertension.
      Elevated serum uric acid levels may be as important as obesity, dyslipidemia,
      diabetes, smoking and reduced kidney function for the development of hypertension
      and should be considered in hypertension prevention programs. 

PMID- 24671019
TI  - Hydrodynamic trails produced by Daphnia: size and energetics.
AB  - This study focuses on quantifying hydrodynamic trails produced by freely swimming
      zooplankton. We combined volumetric tracking of swimming trajectories with planar
      observations of the flow field induced by Daphnia of different size and swimming
      in different patterns. Spatial extension of the planar flow field along the
      trajectories was used to interrogate the dimensions (length and volume) and
      energetics (dissipation rate of kinetic energy and total dissipated power) of the
      trails. Our findings demonstrate that neither swimming pattern nor size of the
      organisms affect the trail width or the dissipation rate. However, we found that
      the trail volume increases with increasing organism size and swimming velocity,
      more precisely the trail volume is proportional to the third power of Reynolds
      number. This increase furthermore results in significantly enhanced total
      dissipated power at higher Reynolds number. The biggest trail volume observed
      corresponds to about 500 times the body volume of the largest daphnids. Trail
      averaged viscous dissipation rate of the swimming daphnids vary in the range of
      1.8 x 10(-6) W/kg to 3.4 x 10(-6) W/kg and the observed magnitudes of total
      dissipated power between 1.3 x 10(-9) W and 1 x 10(-8) W, respectively. Among
      other zooplankton species, daphnids display the highest total dissipated power in
      their trails. These findings are discussed in the context of fluid mixing and
      transport by organisms swimming at intermediate Reynolds numbers.

PMID- 24671020
TI  - Tunable plasmons in atomically thin gold nanodisks.
AB  - The ability to modulate light at high speeds is of paramount importance for
      telecommunications, information processing and medical imaging technologies. This
      has stimulated intense efforts to master optoelectronic switching at visible and
      near-infrared frequencies, although coping with current computer speeds in
      integrated architectures still remains a major challenge. As a partial success,
      mid-infrared light modulation has been recently achieved through gating patterned
      graphene. Here we show that atomically thin noble metal nanoislands can extend
      optical modulation to the visible and near-infrared spectral range. We find
      plasmons in thin metal nanodisks to produce similar absorption cross-sections as
      spherical particles of the same diameter. Using realistic levels of electrical
      doping, plasmons are shifted by about half their width, thus leading to a factor
      of-two change in light absorption. These results, which we substantiate on
      microscopic quantum theory of the optical response, hold great potential for the
      development of electrical visible and near-infrared light modulation in
      integrable, nanoscale devices. 

PMID- 24671021
TI  - Cohort Profile: the Health and Retirement Study (HRS).
AB  - The Health and Retirement Study (HRS) is a nationally representative longitudinal
      survey of more than 37 000 individuals over age 50 in 23 000 households in the
      USA. The survey, which has been fielded every 2 years since 1992, was established
      to provide a national resource for data on the changing health and economic
      circumstances associated with ageing at both individual and population levels.
      Its multidisciplinary approach is focused on four broad topics-income and wealth;
      health, cognition and use of healthcare services; work and retirement; and family
      connections. HRS data are also linked at the individual level to administrative
      records from Social Security and Medicare, Veteran's Administration, the National
      Death Index and employer-provided pension plan information. Since 2006, data
      collection has expanded to include biomarkers and genetics as well as much
      greater depth in psychology and social context. This blend of economic, health
      and psychosocial information provides unprecedented potential to study
      increasingly complex questions about ageing and retirement. The HRS has been a
      leading force for rapid release of data while simultaneously protecting the
      confidentiality of respondents. Three categories of data-public, sensitive and
      restricted-can be accessed through procedures described on the HRS website
      (hrsonline.isr.umich.edu). 

PMID- 24671022
TI  - Composition and thermal analysis of binary mixtures of mee fat and palm stearin.
AB  - Seed fat of Madhuca longifolia known as mee fat (MF) has been considered as a
      potential plant fat for producing fat mixture to simulate the properties of lard.
      A study was carried out to evaluate the effect of addition of palm stearin (PS)
      on the solidification behavior of MF to formulate a mixture to become similar in
      solidification characteristics of lard. Three fat mixtures were prepared by
      blending MF with palm stearin PS in different ratios: MF:PS (99.5:0.5), MF:PS
      (99:1), MF:PS (98:2) (w/w), and identified by the mass ratio of MF to PS. The fat
      mixtures were compared with lard in terms of their fatty acid and triacylglycerol
      compositions, differential scanning calorimetric (DSC) thermal profiles and solid
      fat content (SFC) characteristics. Results showed that there were considerable
      differences between lard and MF:PS fat mixtures with regard to fatty acid and
      triacylglycerol compositions. The increasing proportion of PS in MF:PS fat
      mixtures caused a general increase in SFC at different temperatures with respect
      to the SFC profile of native MF. Of the three binary mixtures, MF:PS (99:1) was
      found to show the least difference to lard in terms of SFC values throughout the
      temperature range. 

PMID- 24671023
TI  - Stability conditions and mechanism of cream soaps: role of glycerol.
AB  - Fatty acids, fatty acid potassium soaps, glycerol and water are essential
      ingredients in the production of stable cream soaps. In this study, the behavior
      of these components in solution was investigated to elucidate the stability
      conditions and mechanism of cream soaps. It was determined that the cream soaps
      were a dispersion of 1:1 acid soap (1:1 molar ratio of potassium soap/fatty acid)
      crystals in the lamellar gel phase, which has confirmed from the phase behavior
      diagrams and small angle X-ray scattering data. Glycerol was crucial ingredient
      in the formation of the lamellar gel phase. The cleansing process of the cream
      soaps was also evaluated using the same diagrams. The structure of the continuous
      phase in cream soaps changed from lamellar gel to a micellar aqueous solution
      upon the addition of water. This structural change during the washing process is
      important in producing the foaming activity of acid soaps to wash away dirt or
      excess fats from the skin surface. 

PMID- 24671024
TI  - Plant growth-promoting fungus Penicillium spp. GP15-1 enhances growth and confers
      protection against damping-off and anthracnose in the cucumber.
AB  - Plant growth-promoting fungi (PGPF) have the potential to confer several benefits
      to plants in terms of growth and protection against pests and pathogens. In the
      present study, we tested whether a PGPF isolate, Penicillium spp. GP15-1 (derived
      from zoysiagrass rhizospheres), stimulates growth and disease resistance in the
      cucumber plant. The use of the barley grain inoculum GP15-1 significantly
      enhanced root and shoot growth and biomass of cucumber plants. A root
      colonization study revealed that GP15-1 was a very rapid and efficient root
      colonizer and was isolated in significantly higher frequencies from the upper
      root parts than from the middle and lower root parts during the first 14 d of
      seedling growth. Inoculating the cucumber seedlings with GP15-1 significantly
      reduced the damping-off disease caused by Rhizoctonia solani, and the disease
      suppression effects of GP15-1 were considerably influenced by the inoculum
      potential of both GP15-1 and the pathogen. Treatment with the barley grain
      inoculum or a cell-free filtrate of GP15-1 increased systemic resistance against
      leaf infection by the anthracnose pathogen Colletotrichum orbiculare, resulting
      in a significant decrease in lesion number and size. Molecular and phylogenetic
      analyses of internal transcribed spacer sequences of the genomic DNA of GP15-1
      revealed that the fungal isolate is a strain of either Penicillium neoechinulatum
      or Penicillium viridicatum. 

PMID- 24671025
TI  - Comparative evaluation of a reverse transcriptase based assay for HIV-1 viral
      load quantitation in resource limited settings.
AB  - Molecular viral load assays are routinely used in high income countries for
      monitoring the copy number of human immunodeficiency virus (HIV) RNA. However,
      they require sophisticated facilities and expensive reagents and instruments.
      Hence, their routine use for patients belonging to resource limited settings is
      difficult and a low cost alternative is the need of the hour. This was a cross
      sectional study that analyzed and compared a reverse transcriptase enzyme based
      assay (Cavidi ExaVir Load version 3) with a real time polymerase chain reaction
      (PCR) assay (Roche COBAS TaqMan) in resource limited settings with subtype C
      predominance. The study included 75 HIV-1 positive treatment naive patients whose
      CD4+ T lymphocytes count was estimated using BD FACS system and viral loads were
      quantified using both Cavidi ExaVir Load assay version 3 and Roche COBAS TaqMan
      Real Time PCR assay. The statistical analysis was performed using the Graph Pad
      Prism 5 software. The difference in the mean log10 viral load values was found to
      be 0.2log10copies/ml. The Bland Altman plot showed a clustering of viral load
      values toward the lower copy range. 78% of the samples had an agreement of <=0.5
      log10 copies/ml and 90.74% of the samples had an agreement of <=1 log10
      copies/ml. Both the assays showed a trend of negative correlation with the CD4+ T
      cell counts. The study found that ExaVir Load assay can be used as an alternative
      to the existing molecular assays in resource limited settings for the purpose of
      routine viral load measurement and monitoring treatment response.

PMID- 24671026
TI  - Direct growth of graphene on quartz substrates for label-free detection of
      adenosine triphosphate.
AB  - We demonstrate that continuous, uniform graphene films can be directly
      synthesized on quartz substrates using a two-temperature-zone chemical vapor
      deposition system and that their layers can be controlled by adjusting the
      precursor partial pressure. Raman spectroscopy and transmission electron
      microscopy confirm the formation of monolayer graphene with a grain size of ~100
      nm. Hall measurements show a room-temperature carrier mobility above 1500 cm2 V(
      1) s(-1). The optical transmittance and conductance of the graphene films are
      comparable to those of transferred metal-catalyzed graphene. The method avoids
      the complicated and skilled post-growth transfer process and allows the graphene
      to be directly incorporated into a fully functional biosensor for label-free
      detection of adenosine triphosphate (ATP). This device shows a fast response time
      of a few milliseconds and achieves a high sensitivity to ATP molecules over a
      very wide range from 0.002 to 5 mM.

PMID- 24671028
TI  - Fatal accidents and injuries among merchant seafarers worldwide.
AB  - BACKGROUND: The British merchant fleet has expanded in recent years but it is not
      known whether this expansion has led to proportionate changes in mortality. AIMS:
      To investigate mortality from accidents and injuries in British merchant
      shipping, to determine whether this has increased in recent years, to compare
      fatal accident rates across British industries and to review fatal accident rates
      in merchant shipping worldwide over the last 70 years. METHODS: Examinations of
      marine accident investigation files, death registers and death inquiry files,
      national mortality statistics, worldwide surveys and review methodology. The main
      outcome measure was the fatal accident rate per 100 000 worker-years. RESULTS: Of
      66 deaths in British shipping from 2003 to 2012, 49 were caused by accidents,
      which largely affected deck ratings. The fatal accident rate in British shipping
      increased by 4.7% per annum from 2003, although this was not significant (95%
      confidence interval: -5.1 to 15.6%). During 2003-12, the fatal accident rate in
      shipping (14.5 per 100 000) was 21 times that in the general British workforce,
      4.7 times that in the construction industry and 13 times that in manufacturing.
      Of 20 merchant fleets worldwide with population-based fatal accident rates, most
      have shown large reductions over time. CONCLUSIONS: The expansion of the British
      merchant fleet in recent years does not appear to have had a major impact on
      fatal accidents. Further preventive measures should target fatalities during
      mooring and towing operations. Internationally, most shipping fleets have over
      time experienced large decreases in fatal accident rates.

PMID- 24671027
TI  - Overexpression of S100A7 protects LPS-induced mitochondrial dysfunction and
      stimulates IL-6 and IL-8 in HaCaT cells.
AB  - BACKGROUND: S100A7 (or psoriasin) is distributed in the cytoplasm of
      keratinocytes of normal human epidermis, and it is overexpressed in many
      epidermal inflammatory diseases. Lipopolysaccharide (LPS) induces mitochondrial
      function changes, which play important roles in multiple cellular mechanisms
      including inflammation. Although S100A7 expression is regulated by various
      factors in the human epidermis during inflammation, whether S100A7 interacts with
      mitochondria in keratinocytes is not clear. OBJECTIVES: Our study was designed to
      investigate whether S100A7 could prohibit mitochondrial dysfunction and stimulate
      cytokines in cultured normal HaCaT cells treated with LPS. RESULTS: We generated
      HaCaT cells that constitutively express enhanced green fluorescence protein
      (EGFP)-S100A7 (S100A7-EGFP) or EGFP alone, as a control. Here, we show that
      S100A7-EGFP HaCaT cells exhibit an increase in mitochondrial DNA (mtDNA) copy
      number and mitochondrial membrane potential (MMP). qRT-PCR revealed that
      expression of three main mitochondrial biogenesis-associated genes was
      significantly increased: PPAR-coactivator-1alpha (PGC-1alpha), the mitochondrial
      transcription factor A (Tfam) and nuclear respiratory factor-1 (NRF1). S100A7
      overexpression increased mtDNA content and effectively increased intracellular
      adenosine 5'-triphosphate (ATP) production, while decreasing reactive oxygen
      species (ROS) generation. S100A7 overexpression also significantly decreased the
      expression of Mfn2 and increased DRP1 expression compared with control EGFP
      cells. S100A7 down-regulated the expression of the autophagy-related proteins
      Beclin-1 and LC3B. S100A7 also increased expression of IL-6 and IL-8 cytokines.
      Knockdown of S100A7 decreased MMP and disrupted mitochondrial homeostasis.
      CONCLUSIONS: These findings demonstrate that S100A7 stimulates mitochondrial
      biogenesis and increases mitochondrial function in HaCaT cells treated with LPS;
      and S100A7 also promotes secretion of IL-6 and IL-8.

PMID- 24671029
TI  - Bridging the gap between continuous sedation until death and physician-assisted
      death: a focus group study in nursing homes in Flanders, Belgium.
AB  - The distinction between continuous sedation until death (CSD) and physician
      assisted death (PAD) has become a topic of medical ethical debate. We conducted 6
      focus groups to examine how nursing home clinicians perceive this distinction.
      For some, the difference is clear whereas others consider CSD a form of
      euthanasia. Another group situates CSD between pain relief and ending life.
      Arguments for these perspectives refer to the following themes: intention, dosage
      of sedative drugs, unconsciousness, and the pace of the dying process. Generally,
      CSD is considered emotionally easier to deal with since it entails a gradual
      dying process. Nursing home clinicians have diverging perceptions of the relation
      between CSD and PAD; some consider CSD to be more than a purely palliative
      measure, that is, also as a means to hasten death.

PMID- 24671030
TI  - The Relation Between the Timing of Palliative Care and the Frequency and Timing
      of Do-Not-Resuscitate Orders Among Cancer Deaths in a Tertiary Care Hospital.
AB  - The medical records of 246 in-hospital cancer deaths were reviewed to explore the
      relation between palliative care (PC) timing and the frequency and timing of do
      not-resuscitate (DNR) designation. The rate of DNR designation was 100% in
      patients referred to PC and 82% in those never referred (P < .001). Patients were
      grouped into 4 groups: early PC (>90 days from PC referral to death),
      intermediate PC (>30-90 days), late PC (<=30 days), and no PC. The median DNR to
      death time was 96, 41, 11, and 3 days, respectively (P < .001). The proportion of
      intensive care unit (ICU) deaths was 0%, 1%, 3%, and 27%, respectively (P <
      .001). In conclusion, in a tertiary care hospital, earlier PC was associated with
      earlier DNR designation and less frequent ICU deaths among in-hospital cancer
      deaths. 

PMID- 24671031
TI  - Pantoea agglomerans endophthalmitis: clinical features and outcomes.
AB  - PURPOSE: To determine the clinical profile and outcomes of patients with Pantoea
      agglomerans endophthalmitis as seen at a tertiary eye care center in India.
      METHODS: Retrospective observational case series. Data collected included
      demographics, history, the initial and final corrected distance visual acuity,
      details of the ocular and systemic examination, surgeries performed, and the
      final anatomical outcome. The final corrected distance visual acuity and the
      anatomical outcome were the outcome measures. RESULTS: Four patients had
      traumatic endophthalmitis; the fifth developed endophthalmitis after cataract
      surgery. All patients were men with a mean age of 34.24 +/- 23.34 years. Three
      patients had corneal laceration and traumatic cataract. All patients underwent
      vitreous sampling with intraocular antibiotic injection with or without
      lensectomy and corneal wound repair. The visual acuity at presentation ranged
      from hand motion to perception of light. One patient ended up with phthisis in
      the affected eye. One patient developed postoperative retinal detachment and
      underwent successful surgery. The final visual acuity ranged from 20/25 to no
      light perception. CONCLUSION: P. agglomerans is a likely source of infection in
      traumatic and postoperative cases. Though variable, it appears sensitive to
      common antibiotics. The visual and anatomical prognosis seems fair in most cases.
      Special care needs to be taken to ensure the organism is not missed, given the
      rarity of the condition and the isolation techniques required.

PMID- 24671032
TI  - A simple education tool for ventricular assist device patients and their
      caregivers.
AB  - BACKGROUND: Ventricular assist devices (VADs) have become an important therapy in
      the management of patients with end-stage heart failure. Driveline infection is
      the most common late-onset complication in this group of patients. Patients and
      their caregivers require education regarding management of the driveline to
      reduce the risk of infection when they are discharged home with a VAD. PURPOSE:
      The aim of this study was to develop an educational booklet on VAD driveline care
      for patients and their caregivers. A literature review was undertaken to explore
      the availability of patient education material pertaining to driveline management
      and to update evidence-informed knowledge that could potentially reduce infection
      rates in these patients. This information was evaluated by peers, patients, and
      caregivers to produce the final colored booklet. CONCLUSIONS: Driveline care is
      not comprehensively discussed in the literature and lacks detail in the
      particulars of wound care, patient education, and the adaptation of driveline
      care to the patient's home environment. An educational booklet was designed to
      convey what is currently known about preventing driveline infections to those who
      are responsible for providing the required daily care. Evaluation of patient
      education material by those using the material is essential. As with all written
      material, the information will require updating as new evidence becomes
      available. CLINICAL IMPLICATIONS: Managing driveline infection risk for patients
      at home with extended therapy is a critical nursing issue in improving morbidity
      and mortality. After VAD implantation, patients and caregivers must be educated
      about the ongoing care of the driveline exit site to minimize the risk of
      infection. A rigorously developed and patient-evaluated educational booklet on
      driveline exit site care can be a valuable reference tool for patients and
      caregivers after hospital discharge.

PMID- 24671033
TI  - Technologies for detecting falsified and substandard drugs in low and middle
      income countries.
AB  - Falsified and substandard drugs are a global health problem, particularly in low-
      and middle-income countries (LMIC) that have weak pharmacovigilance and drug
      regulatory systems. Poor quality medicines have important health consequences,
      including the potential for treatment failure, development of antimicrobial
      resistance, and serious adverse drug reactions, increasing healthcare costs and
      undermining the public's confidence in healthcare systems. This article presents
      a review of the methods employed for the analysis of pharmaceutical formulations.
      Technologies for detecting substandard and falsified drugs were identified
      primarily through literature reviews. Key-informant interviews with experts
      augmented our methods when warranted. In order to aid comparisons, technologies
      were assigned a suitability score for use in LMIC ranging from 0-8. Scores
      measured the need for electricity, need for sample preparation, need for
      reagents, portability, level of training required, and speed of analysis.
      Technologies with higher scores were deemed the most feasible in LMICs. We
      categorized technologies that cost $10,000 USD or less as low cost, $10,000
      100,000 USD as medium cost and those greater than $100,000 USD as high cost
      technologies (all prices are 2013 USD). This search strategy yielded information
      on 42 unique technologies. Five technologies were deemed both low cost and had
      feasibility scores between 6-8, and an additional four technologies had medium
      cost and high feasibility. Twelve technologies were deemed portable and therefore
      could be used in the field. Many technologies can aid in the detection of
      substandard and falsified drugs that vary from the simplest of checklists for
      packaging to the most complex mass spectrometry analyses. Although there is no
      single technology that can serve all the requirements of detecting falsified and
      substandard drugs, there is an opportunity to bifurcate the technologies into
      specific niches to address specific sections within the workflow process of
      detecting products. 

PMID- 24671034
TI  - Some like it cold: understanding the survival strategies of psychrophiles.
AB  - Much of the Earth's surface, both marine and terrestrial, is either periodically
      or permanently cold. Although habitats that are largely or continuously frozen
      are generally considered to be inhospitable to life, psychrophilic organisms have
      managed to survive in these environments. This is attributed to their innate
      adaptive capacity to cope with cold and its associated stresses. Here, we review
      the various environmental, physiological and molecular adaptations that
      psychrophilic microorganisms use to thrive under adverse conditions. We also
      discuss the impact of modern "omic" technologies in developing an improved
      understanding of these adaptations, highlighting recent work in this growing
      field. 

PMID- 24671035
TI  - ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate
      mitophagy.
AB  - Autophagy eliminates dysfunctional mitochondria in an intricate process known as
      mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s)
      and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is
      upregulated and translocates to fragmented mitochondria upon mitophagy induction
      by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts
      with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to
      LC3. A ULK1-binding-deficient mutant of FUNDC1 prevents ULK1 translocation to
      mitochondria and inhibits mitophagy. Finally, kinase-active ULK1 and a phospho
      mimicking mutant of FUNDC1 rescue mitophagy in ULK1-null cells. Thus, we conclude
      that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1
      phosphorylation by ULK1 is crucial for mitophagy. 

PMID- 24671037
TI  - Pyridinylboronic acid-functionalized organic-silica hybrid monolithic capillary
      for the selective enrichment and separation of cis-diol-containing biomolecules
      at acidic pH.
AB  - Boronate affinity chromatography (BAC) is a unique means for the selective
      separation and enrichment of 1,2 and 1,3 cis-diol-containing compounds. However,
      conventional boronate affinity materials require a basic binding pH
      (usually>=8.5), which gives rise to not only inconvenience in operation but also
      the risk of degradation of labile compounds. Although the applicable pH has been
      expanded to 5.0 in recent years, the current boronate affinity materials still
      fail to meet the acidic pH end of frequently used biosamples, particularly urine
      (pH 4.5). In this study, we report a 3-pyridylboronic acid-functionalized organic
      silica hybrid monolithic capillary that exhibited a binding pH of 4.5, the lowest
      so far in BAC. Such a binding pH enabled direct extraction of cis-diol-containing
      biomolecules such as nucleosides from urine samples without pH adjustment. The
      boronate affinity monolithic capillary showed enhanced affinity toward negatively
      charged cis-diol-containing analytes such as ribonucleotides. Moreover, it could
      function as an anion exchanger at acidic pH (~2). The column was found to retain
      multiple compounds from urine, which can be assumed to be at least mostly if not
      entirely cis-diol-containing compounds. 

PMID- 24671036
TI  - Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor
      patients.
AB  - Epigenome-wide studies of DNA methylation using blood-derived DNA from cancer
      patients are complicated by the heterogeneity of cell types within blood and the
      associated cell lineage specification of DNA methylation signatures. Here, we
      applied a novel set of analytic approaches to assess the association between
      cancer case-status and DNA methylation adjusted for leukocyte variation using
      blood specimens from three case-control cancer studies (bladder: 223 cases, 205
      controls; head and neck: 92 cases, 92 controls; and ovarian: 131 cases, 274
      controls). Using previously published data on leukocyte-specific CpG loci and a
      recently described approach to deconvolute subject-specific blood composition, we
      performed an epigenome-wide analysis to examine the association between blood
      based DNA methylation patterns and each of the three aforementioned solid tumor
      types adjusted for cellular heterogeneity in blood. After adjusting for leukocyte
      profile in our epigenome-wide analysis, the omnibus association between case
      status and methylation was significant for all three studies (bladder cancer: P =
      0.047; HNSCC: P = 0.013; ovarian cancer: P = 0.0002). Subsequent analyses
      revealed that CpG sites associated with cancer were enriched for transcription
      factor binding motifs involved with cancer-associated pathways. These results
      support the existence of cancer-associated DNA methylation profiles in the blood
      of solid tumor patients that are independent of alterations in normal leukocyte
      distributions. Adoption of the methods developed here will make it feasible to
      rigorously assess the influence of variability of normal leukocyte profiles when
      investigating cancer related changes in blood-based epigenome-wide association
      studies. 

PMID- 24671038
TI  - A method-of-moments formulation for describing hydrodynamic dispersion of analyte
      streams in free-flow zone electrophoresis.
AB  - In this work, a method-of-moments formulation has been presented for estimating
      the dispersion of analyte streams as they migrate through a free-flow zone
      electrophoresis (FFZE) channel under laminar flow conditions. The current
      analysis considers parallel-plate based FFZE systems with an applied pressure
      gradient along the channel length for sample and carrier electrolyte transport,
      and an external electric field in the transverse direction for enabling the
      electrophoretic separation. A closed-form expression has been derived using this
      mathematical approach for describing the spatial variance of sample streams as a
      function of their position in the separation chamber at steady state. This
      expression predicts that the hydrodynamic dispersion component in an FFZE assay
      scales as Pex(2) where Pex denotes the Peclet number based on the analyte's
      transverse electrophoretic migration velocity rather than its longitudinal
      pressure-driven flow speed as expected in transport processes induced by a
      pressure-gradient. Interestingly however, the coefficient multiplying this
      dimensionless group, i.e., 1/210, is identically equal to the constant preceding
      the square of the relevant Peclet number in the latter case (i.e., Peclet number
      based on the longitudinal flow speed). It must be noted that while the
      mathematical analysis reported in this work is only valid for FFZE systems in the
      absence of any unwanted Joule heating, pressure-driven cross-flow and/or
      differences in the electrical conductivity between the sample and carrier
      electrolyte, it can also be applied to numerically estimate the effect of these
      factors on the separation resolution of the assay.

PMID- 24671039
TI  - Coupling of deoxyribonucleic acid to solid supports using 3' terminal ribose
      incorporation.
AB  - To develop a new form of DNA coupling under mild reaction and coupling
      conditions, DNA oligonucleotides were synthesized containing a 3' ribonucleotide.
      Upon reaction with millimolar sodium metaperiodate (NaIO4), the ribose is
      oxidized to a dialdehyde at pH 6.8. This reaction is complete in 30min, is
      quenched with millimolar sodium metabisulfite (Na2S2O5) and is then suitable for
      coupling to hydrazide-agarose supports. Coupling occurs with a half-time of 27min
      and 80% couples in 2h. The EP18 oligonucleotide which binds to the CAAT enhancer
      binding protein (C/EBP) was synthesized with a 3' ribose (rEP18) and coupled to
      hydrazide-agarose. The columns prepared show no significant loss of the
      oligonucleotide after 50 days. A crude bacterial extract from cells expressing a
      chimeric fusion protein of GFP-C/EBP was applied to the columns and eluted with
      different salt concentrations. The active protein elutes in 0.5M NaCl and SDS
      PAGE/silver stained gels show a single major band which comigrates with GFP-C/EBP
      as well as three minor contaminants. This provides a new alternative way of
      coupling DNA to solid supports using mild chemistry which is non-detrimental to
      the DNA and can be performed if required in the presence of nuclear extract. 

PMID- 24671040
TI  - Development of a one-step integrated pressurized liquid extraction and cleanup
      method for determining polycyclic aromatic hydrocarbons in marine sediments.
AB  - A rapid and accurate one-step integrated pressurized liquid extraction (PLE) and
      cleanup method was developed and validated for 34 polycyclic aromatic
      hydrocarbons in marine sediments, giving an extract that could be analyzed by gas
      chromatography-mass spectrometry without further cleanup. Marine sediment (5 g)
      was loaded into the stainless-steel extraction cell above activated copper (5 g)
      and activated silica gel (5 g). An extraction temperature of 100 degrees C and
      two 5 min extraction cycles using a 4:1 (v/v) hexane-dichloromethane mixture gave
      a good extraction efficiency. The integrated method gave extracts that were as
      clean as those obtained using PLE, followed by separate activated copper and
      silica gel cleanups. The method was validated, in terms of its accuracy,
      precision, and application using a certified reference material (NIST SRM 1944),
      marine sediments spiked at low and high concentrations, and contaminated harbor
      sediments. The mean recoveries were 92% and 94% for the low and high spike
      concentrations, respectively, and the accuracy was good (giving a mean of 86% of
      the certified reference material concentrations). The method developed gave a
      precision and accuracy equal to or better than the precision and accuracy found
      using PLE with separate cleanups. The method developed gives a shorter sample
      preparation time and uses much less solvent than PLE and separate cleanups.

PMID- 24671041
TI  - Separation and purification of linear covalently closed deoxyribonucleic acid by
      Q-anion exchange membrane chromatography.
AB  - We have constructed an in vivo system for rapid, scalable production of linear
      covalently closed (LCC) DNA from precursor circular covalently closed (CCC)
      plasmid DNA (pDNA) that offers a stronger safety profile compared to conventional
      CCC pDNA vectors. In the processing of LCC DNA products from the precursor CCC
      pDNA, LCC minivector DNA is produced in addition to other precursor DNA species
      and isoforms. DNA purification by anion exchange chromatography (AEC) attains
      high vector purity, making it an efficient and valuable approach to purification
      processes for the production of clinical grade DNA. Membrane chromatography
      offers significant advantages over traditional column chromatography including
      large convective pores, higher binding capacities, high throughput, scalable
      purification processes, and disposability. A hydrogel-based strong Q-anion
      exchange membrane for anion exchange chromatography can bind DNA with high
      capacity and recovery upon purification. We exploited these membrane properties
      in the separation of DNA sizes and isoforms to purify LCC DNA. We employed a NaCl
      concentration gradient at varying flow rates to successfully achieve effective
      separation of parental supercoiled CCC pDNA from processed isogenic LCC
      derivatives generated by the LCC DNA vector production system. We propose that
      anion exchange membrane chromatography is well positioned to play an integral
      role in large scale LCC DNA vector purification, successfully separating vectors
      by DNA isoforms. 

PMID- 24671042
TI  - Determination of the average volumetric flow rate in supercritical fluid
      chromatography.
AB  - This work reviews and discusses controversies and errors made in the
      determination of the average volumetric flow rate of a compressible mobile phase
      forced to flow through a chromatographic column. Proper estimates of the
      volumetric flow rate, which obviously changes along the column, are keys to
      understanding the retention mechanism that takes place inside the column and to
      achieve repeatable and reproducible separations. Each step of the calculation
      process will be discussed in detail, including how to estimate the variations of
      the pressure and the temperature along the column. The determination of the
      average volumetric flow rate requires the knowledge of the average density of the
      mobile phase and of its mass flow rate. The calculations were carried out under
      various experimental conditions, including different column temperatures and
      inlet pressures. The estimated values of the volumetric flow rate are validated
      by the conversion of the retention times to the retention volumes of nitrous
      oxide peaks, which is valid since this compound is assumed to be non retained,
      which makes it a hold-up time marker. 

PMID- 24671043
TI  - Enhancement of capillary electrochromatographic separation performance by
      conductive polymer in a layer-by-layer fabricated graphene stationary phase.
AB  - In this work, we fabricated a novel graphene-based capillary column for open
      tubular capillary electrochromatography (OT-CEC) by a layer-by-layer strategy. To
      immobilize graphene onto the inner surface of silica capillary, a bio-inspired
      method was first used to functionalize the capillary surface with a layer of
      polydopamine (PDA). Graphene oxide (GO) was then introduced and can covalently
      react with polydopamine, realizing immobilization of graphene as a result. To
      enhance the modification efficiency of polydopamine, a conductive polymer,
      polyaniline (PANI) was introduced to be a sub-layer; polydopamine was then
      introduced following with GO, to generate a multilayer GO-PDA-PANI@capillary.
      Interestingly, separation efficiency of the graphene-based capillary was enhanced
      significantly by using conductive PANI as a sub-layer. The morphology of
      different layers modified on the capillary column was characterized by scanning
      electron microscopy (SEM). The electroosmotic flow (EOF) characteristics of
      capillaries modified with different layers were also investigated by varying the
      pH value of mobile phase. GO-PDA-PANI@capillary showed good separation efficiency
      towards alkylbenzenes by OT-CEC mode, with theoretic plate numbers up to 133,918
      for benzene. The separation was found to follow a reversed-phase chromatographic
      retention mechanism. Repeatability of the GO-PDA-PANI@capillary was studied, with
      relative standard deviations for intra-day and inter-day runs less than 2.89%,
      and column-to-column runs less than 6.17%. The separation performance of GO-PDA
      PANI@capillary was also compared with that of the reported graphene modified
      capillary. 

PMID- 24671044
TI  - "Honor," collectivity, and agnation: emerging risk factors in "honor"-based
      violence.
AB  - "Honor"-based violence (HBV) is increasingly recognized as form of violence
      against women and girls, but is neither fully conceptualized nor integrated into
      risk management strategies that are increasingly used to address gender-based
      violence in Europe and Anglophone states. This article will argue that there are
      grounds for the differentiation of HBV as a sub-category of gender-based violence
      which may affect risk management. Research was based in an analysis of 40 case
      files taken from Arabic- and Kurdish-speaking clients of a London nongovernment
      organization (NGO) providing services to women facing violence. Interrelations
      were found between "honor," agnation, and collectivity in their experiences of
      violence, with ramifications for service provision. 

PMID- 24671046
TI  - Endodermal differentiation of human pluripotent stem cells to insulin-producing
      cells in 3D culture.
AB  - Insulin-producing cells (IPCs) derived from human pluripotent stem cells (hPSCs)
      may be useful in cell therapy and drug discovery for diabetes. Here, we examined
      various growth factors and small molecules including those previously reported to
      develop a robust differentiation method for induction of mature IPCs from hPSCs.
      We established a protocol that induced PDX1-positive pancreatic progenitor cells
      at high efficiency, and further induced mature IPCs by treatment with forskolin,
      dexamethasone, Alk5 inhibitor II and nicotinamide in 3D culture. The cells that
      differentiated into INSULIN-positive and C-PEPTIDE-positive cells secreted
      insulin in response to glucose stimulation, indicating a functional IPC
      phenotype. We also found that this method was applicable to different types of
      hPSCs. 

PMID- 24671047
TI  - Expressed glycosylphosphatidylinositol-anchored horseradish peroxidase identifies
      co-clustering molecules in individual lipid raft domains.
AB  - Lipid rafts that are enriched in glycosylphosphatidylinositol (GPI)-anchored
      proteins serve as a platform for important biological events. To elucidate the
      molecular mechanisms of these events, identification of co-clustering molecules
      in individual raft domains is required. Here we describe an approach to this
      issue using the recently developed method termed enzyme-mediated activation of
      radical source (EMARS), by which molecules in the vicinity within 300 nm from
      horseradish peroxidase (HRP) set on the probed molecule are labeled. GPI-anchored
      HRP fusion proteins (HRP-GPIs), in which the GPI attachment signals derived from
      human decay accelerating factor and Thy-1 were separately connected to the C
      terminus of HRP, were expressed in HeLa S3 cells, and the EMARS reaction was
      catalyzed by these expressed HRP-GPIs under a living condition. As a result,
      these different HRP-GPIs had differences in glycosylation and localization and
      formed distinct clusters. This novel approach distinguished molecular clusters
      associated with individual GPI-anchored proteins, suggesting that it can identify
      co-clustering molecules in individual raft domains. 

PMID- 24671048
TI  - Solid bioneedle-delivered influenza vaccines are highly thermostable and induce
      both humoral and cellular immune responses.
AB  - The potential of bioneedles to deliver influenza vaccines was investigated. Four
      influenza vaccine formulations were screened to determine the optimal formulation
      for use with bioneedles. The stability of the formulations after freeze-drying
      was checked to predict the stability of the influenza vaccines in the bioneedles.
      Subunit, split, virosomal and whole inactivated influenza (WIV) vaccine were
      formulated and lyophilized in bioneedles, and subsequently administered to
      C57BL/6 mice. Humoral and cellular immune responses were assessed after
      vaccination. The thermostability of lyophilized vaccines was determined after one
      month storage at elevated temperatures. Bioneedle influenza vaccines induced HI
      titers that are comparable to those induced by intramuscular WIV vaccination.
      Delivery by bioneedles did not alter the type of immune response induced by the
      influenza vaccines. Stability studies showed that lyophilized influenza vaccines
      have superior thermostability compared to conventional liquid vaccines, and
      remained stable after one-month storage at 60 degrees C. Influenza vaccines
      delivered by bioneedles are a viable alternative to conventional liquid influenza
      vaccines. WIV was determined to be the most potent vaccine formulation for
      administration by bioneedles. Lyophilized influenza vaccines in bioneedles are
      independent of a cold-chain, due to their increased thermostability, which makes
      distribution and stockpiling easier. 

PMID- 24671049
TI  - The effect of a community-based self-help multimodal behavioral intervention in
      Korean American seniors with high blood pressure.
AB  - BACKGROUND: Great strides have been made in improving heart health in the United
      States during the last 2 decades, yet these strides have not encompassed many
      ethnic minority populations. There are significant health disparity gaps stemming
      from both a paucity of valid research and a lack of culturally sensitive
      interventions. In particular, many Korean Americans with chronic illnesses
      encounter difficulty navigating the healthcare system because of limited health
      literacy. METHODS: The effect of a multimodal Self-Help Intervention Program on
      the Control of High Blood Pressure (HBP) was tested in a community-based clinical
      trial for Korean American seniors. Of 440 seniors enrolled, 369 completed the
      study (184 in the intervention group and 185 in the control group; mean age =
      70.9+/-5.3 years). The intervention group received 6 weekly educational sessions
      on HBP management skill building, including health literacy training, followed by
      telephone counseling and home blood pressure (BP) monitoring for 12 months.
      RESULTS: Findings support that the Self-Help Intervention Program on the Control
      of HBP was effective in controlling BP in this ethnic/linguistic minority
      population. The BP control rates for the intervention and control groups were
      49.5% vs. 43.2% at baseline, 58.5% vs. 42.4% at 6 months, 67.9% vs. 52.5% at 12
      months, and 54.3% vs. 53.0% at 18 months. Significant changes were observed over
      time in some psychobehavioral outcomes, including self-efficacy for BP control,
      medication adherence behavior, HBP knowledge, and depression. CONCLUSIONS: The
      study findings suggest that the multimodal Self-Help Intervention Program on the
      Control of HBP is effective at promoting optimal HBP control for this
      ethnic/linguistic minority population. CLINICAL TRIALS REGISTRY: NCT00406614.

PMID- 24671050
TI  - Serum albumin and prealbumin predict the poor outcome of traumatic brain injury.
AB  - BACKGROUND: Serum albumin and prealbumin are both negative acute-phase reactants,
      and usually at low levels in stress. We aim to determine their predictive values
      for poor outcome of traumatic brain injury (TBI). METHODS: A total of 326
      patients of TBI were enrolled and followed-up by telephone 6 months after
      discharge. They were divided into a favorable group (GOS: 3 to 5) and an
      unfavorable group (GOS: 1 to 2). Serum albumin and prealbumin were measured from
      vein blood within 24 h after admission. RESULTS: Ninety one (27.9%) patients were
      with poor outcome (GOS: 1 to 2). The unfavorable group had lower albumin and
      prealbumin (P<0.001). Albumin and prealbumin were both positively correlated with
      GCS (r = 0.489, P<0.001; r = 0.222, P<0.001, respectively) and GOS (r = 0.518,
      P<0.001; r = 0.314, P<0.001, respectively). After adjustment for confounding
      factors, the odds ratios of albumin and prealbumin were 0.866, 95% CI: 0.829 to
      0.904 and 0.990, 95% CI: 0.985 to 0.995, respectively. In subgroup of GCS<=8 (n =
      101), the crude and adjusted odds ratios of serum albumin were both statistically
      significant (P = 0.027, P = 0.033, respectively), while prealbumin were not (P =
      0.553, P = 0.576, respectively). The AUC of albumin for predicting poor outcome
      was 0.762, 95% CI: 0.712 to 0.807, which was significantly higher than that of
      prealbumin (0.664, 95% CI: 0.610 to 0.715). In analyses of all patients and
      subgroup of GCS<=8, the AUCs of serum albumin were both significantly higher than
      those of prealbumin (P = 0.001, P = 0.045, respectively). CONCLUSIONS: Both serum
      albumin and prealbumin could predict the poor outcome of TBI, but the former is
      much better, especially, in patients with severe TBI.

PMID- 24671051
TI  - ALDH maintains the stemness of lung adenoma stem cells by suppressing the
      Notch/CDK2/CCNE pathway.
AB  - OBJECTIVE: To evaluate the expression of ALDH1A1 in lung adenoma stem cells
      (LASCs) and maintenance of their stemness through the Notch pathway. METHODS:
      LASCs (A549s) were isolated from lung adenoma cells (A549) and identified by
      their coexpression of CD133 and CD326 and their capacity formulti-directional
      differentiation. Expression of ALDH1A1 in A549 and A549s cells were evaluated by
      Real-time PCR. Effects of ALDH1A1 upregulation in A549 cells and its
      downregulation in A549s cells on the clonogenicity and cell cycle were assessed
      by colony-forming unit assay. Moreover, the effects of ALDH1A1 on the Notch
      pathway, and thus on the cell cycle, were studied. RESULTS: A549s cells were
      successfully isolated and identified.ALDH1A1expression was significantly higher
      in A549s than in A549 cells. Clonogenicity was significantly decreased in A549s
      cells treated with ALDH1A1 siRNA. Duration of the G1 stage of the cell cycle
      increased after ALDH1A1 was overexpressed, or decreased with ALDH1A1 siRNA.
      ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 expression levels were higher in
      A549s cells than in A549 cells. Expression of Notch1, -2, and -3, CDK2, and CCNE1
      was significantly decreased by upregulation of ALDH1A1 in A549 cells, but
      increased by its interruption in A549s cells. When Notch3 or CDK2 expression was
      downregulated, the expression levels of ALDH1A1, Notch1, -2, and -3, CDK2, and
      CCNE1 were reduced in all cell types. CONCLUSION: ALDH1A1 expression improved
      clonogenicity and inhibited the cell cycle, maintaining the stemness of the A549s
      cells; this may involve suppression of the Notch/CDK2/Cyclin pathway.

PMID- 24671052
TI  - Humpback whale populations share a core skin bacterial community: towards a
      health index for marine mammals?
AB  - Microbes are now well regarded for their important role in mammalian health. The
      microbiology of skin--a unique interface between the host and environment--is a
      major research focus in human health and skin disorders, but is less explored in
      other mammals. Here, we report on a cross-population study of the skin-associated
      bacterial community of humpback whales (Megaptera novaeangliae), and examine the
      potential for a core bacterial community and its variability with host
      (endogenous) or geographic/environmental (exogenous) specific factors. Skin
      biopsies or freshly sloughed skin from 56 individuals were sampled from
      populations in the North Atlantic, North Pacific and South Pacific oceans and
      bacteria were characterized using 454 pyrosequencing of SSU rRNA genes.
      Phylogenetic and statistical analyses revealed the ubiquity and abundance of
      bacteria belonging to the Flavobacteria genus Tenacibaculum and the
      Gammaproteobacteria genus Psychrobacter across the whale populations. Scanning
      electron microscopy of skin indicated that microbial cells colonize the skin
      surface. Despite the ubiquity of Tenacibaculum and Psychrobater spp., the
      relative composition of the skin-bacterial community differed significantly by
      geographic area as well as metabolic state of the animals (feeding versus
      starving during migration and breeding), suggesting that both exogenous and
      endogenous factors may play a role in influencing the skin-bacteria. Further,
      characteristics of the skin bacterial community from these free-swimming
      individuals were assembled and compared to two entangled and three dead
      individuals, revealing a decrease in the central or core bacterial community
      members (Tenacibaculum and Psychrobater spp.), as well as the emergence of
      potential pathogens in the latter cases. This is the first discovery of a cross
      population, shared skin bacterial community. This research suggests that the skin
      bacteria may be connected to humpback health and immunity and could possibly
      serve as a useful index for health and skin disorder monitoring of threatened and
      endangered marine mammals.

PMID- 24671054
TI  - Effect of Sedum sarmentosum BUNGE extract on aristolochic acid-induced renal
      tubular epithelial cell injury.
AB  - Aristolochic acid (AA) is known as a potent mutagen that induces significant
      cytotoxic and mutagenic effects on renal tubular epithelial cells. Clinically,
      the persistent injury of AA results in the infiltration of inflammatory cells,
      epithelial-to-mesenchymal transition (EMT), and renal tubulointerstitial
      fibrosis. There are no truly effective pharmaceuticals. In this study, we
      investigated the potential role of the extract of Sedum sarmentosum Bunge (SSB),
      a traditional Chinese herbal medicine, on rat tubuloepithelial (NRK-52E) cells
      after AA injury in vitro. Evidence revealed that AA induced mitochondrial-pathway
      mediated cellular apoptosis, accompanied by cell proliferation in a feedback
      mechanism. Treatment with SSB also induced cells to enter early apoptosis, but
      inhibited cell proliferation. In cultured NRK-52E cells, AA induced the imbalance
      of MMP-2/TIMP-2 and promoted EMT and ECM accumulation. SSB treatment
      significantly alleviated AA-induced NRK-52E cells fibrosis-like appearance,
      inhibited the induction of EMT, and deposition of ECM. SSB also decreased the
      activity of the NF-kappaB signaling pathway, resulting in down-regulated
      expression of NF-kappaB-controlled chemokines and pro-inflammatory cytokines,
      including MCP-1, MIF, and M-CSF, which may regulate the macrophage-mediated
      inflammatory reaction during renal fibrosis in vivo. Therefore, these findings
      suggest that SSB exerts protective effects against AA-induced tubular epithelial
      cells injury through suppressing the synthesis of inflammatory factors, EMT, and
      ECM production. 

PMID- 24671053
TI  - Telmisartan treatment ameliorates memory deficits in streptozotocin-induced
      diabetic mice via attenuating cerebral amyloidosis.
AB  - Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported
      to exert beneficial effects on the central nervous system (CNS). However, the
      effect of telmisartan on cognitive impairment associated with type 1 diabetes is
      not well known. Here, we examined the possibility that telmisartan could improve
      memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced
      diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM)
      task exhibited a significant decline of spatial learning and memory. Oral
      administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg)
      significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan
      treatment markedly reduced Abeta42, APP, BACE1, RAGE, and NF-kappaB p65 of the
      hippocampus and cortex, but did not beneficially affect hyperglycemia and
      hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic
      mice. Taken together, our findings suggest that telmisartan ameliorates memory
      deficits in type 1 diabetic mice, at least partly because of attenuation of
      amyloidosis in the brain.

PMID- 24671055
TI  - Pharmacological characterization of standard analgesics on oxaliplatin-induced
      acute cold hypersensitivity in mice.
AB  - Oxaliplatin, a platinum-based chemotherapeutic agent, causes an acute peripheral
      neuropathy triggered by cold in almost all patients during or within hours after
      its infusion. We recently reported that a single administration of oxaliplatin
      induced cold hypersensitivity 2 h after the administration in mice. In this
      study, we examined whether standard analgesics relieve the oxaliplatin-induced
      acute cold hypersensitivity. Gabapentin, tramadol, mexiletine, and calcium
      gluconate significantly inhibited and morphine and milnacipran decreased the
      acute cold hypersensitivity, while diclofenac and amitriptyline had no effects.
      These results suggest that gabapentin, tramadol, mexiletine, and calcium
      gluconate are effective against oxaliplatin-induced acute peripheral neuropathy. 

PMID- 24671056
TI  - LAT1 is a central transporter of essential amino acids in human umbilical vein
      endothelial cells.
AB  - Endothelial cell proliferation supporting angiogenesis requires sufficient
      nutrient supply because of facilitated intracellular metabolism. However, little
      is known about the mechanism for the promotion of nutrient incorporation in
      proliferating endothelial cells. Here we show that L-type amino acid transporter
      1 (LAT1) is a major transporter of essential amino acids in human umbilical vein
      endothelial cells (HUVECs). Growing HUVECs express a certain level of LAT1. A
      LAT1-specific inhibitor suppressed leucine uptake, cell proliferation, and tube
      formation of HUVECs. Therefore, LAT1 acts to support effective uptake of amino
      acids, which is critical for the optimal function of HUVECs for angiogenesis. 

PMID- 24671058
TI  - Introducing the Institute of Physics in Engineering and Medicine (IPEM).

PMID- 24671059
TI  - High time for advancing marijuana research.

PMID- 24671057
TI  - Kinship and social behavior of lowland tapirs (Tapirus terrestris) in a central
      Amazon landscape.
AB  - We tested the hypothesis that tapirs tolerate individuals from adjacent and
      overlapping home ranges if they are related. We obtained genetic data from fecal
      samples collected in the Balbina reservoir landscape, central Amazon. Samples
      were genotyped at 14 microsatellite loci, of which five produced high quality
      informative genotypes. Based on an analysis of 32 individuals, we inferred a
      single panmictic population with high levels of heterozygosity. Kinship analysis
      identified 10 pairs of full siblings or parent-offspring, 10 pairs of half
      siblings and 25 unrelated pairs. In 10 cases, the related individuals were
      situated on opposite margins of the reservoir, suggesting that tapirs are capable
      of crossing the main river, even after damming. The polygamous model was the most
      likely mating system for Tapirus terrestris. Moran's I index of allele sharing
      between pairs of individuals geographically close (<3 km) was similar to that
      observed between individual pairs at larger distances (>3 km). Confirming this
      result, the related individuals were not geographically closer than unrelated
      ones (W = 188.5; p = 0.339). Thus, we found no evidence of a preference for being
      close to relatives and observed a tendency for dispersal. The small importance of
      relatedness in determining spatial distribution of individuals is unusual in
      mammals, but not unheard of. Finally, non-invasive sampling allowed efficient
      access to the genetic data, despite the warm and humid climate of the Amazon,
      which accelerates DNA degradation. 

PMID- 24671060
TI  - Following your heart.

PMID- 24671061
TI  - So many progenitors, so little myelin.

PMID- 24671062
TI  - Dark matter of the bulb.

PMID- 24671063
TI  - Useful dynamic regimes emerge in recurrent networks.

PMID- 24671064
TI  - Go means green.

PMID- 24671065
TI  - A solution to dependency: using multilevel analysis to accommodate nested data.
AB  - In neuroscience, experimental designs in which multiple observations are
      collected from a single research object (for example, multiple neurons from one
      animal) are common: 53% of 314 reviewed papers from five renowned journals
      included this type of data. These so-called 'nested designs' yield data that
      cannot be considered to be independent, and so violate the independency
      assumption of conventional statistical methods such as the t test. Ignoring this
      dependency results in a probability of incorrectly concluding that an effect is
      statistically significant that is far higher (up to 80%) than the nominal alpha
      level (usually set at 5%). We discuss the factors affecting the type I error rate
      and the statistical power in nested data, methods that accommodate dependency
      between observations and ways to determine the optimal study design when data are
      nested. Notably, optimization of experimental designs nearly always concerns
      collection of more truly independent observations, rather than more observations
      from one research object. 

PMID- 24671067
TI  - Behavioral and neural correlates of cognitive-affective function during late
      pregnancy: an Event-Related Potentials study.
AB  - The present study was aimed at identifying potential behavioral and neural
      correlates of cognitive and emotional processing during pregnancy using scalp
      recorded Event-Related Potentials (ERPs). We used a 4-stimulus visual oddball
      task, combining emotional and non-emotional stimuli. Responses to target and non
      target stimuli were compared across groups of 17 pregnant women on their third
      trimester and 19 non-pregnant women. Participants also completed a non-emotional
      test of sustained attention and response inhibition; the Online Continuous
      Performance Test (OCPT). Pregnant women had poorer performance than controls on
      most indices of the OCPT and the oddball task. ERP results indicated that
      pregnancy significantly interacted with the type of target stimuli. Results of
      the P3 component have demonstrated a comparative reduction in P3 amplitude in
      pregnant women in response to the target emotional faces but not in response to
      the target shapes. Moreover, among pregnant women, P3 amplitude was greater for
      the target shapes than for the target faces, while in non-pregnant women P3
      amplitude was greater for the target faces than for the target shapes. Results of
      the N170 component showed that N170 to faces, but not to shapes, was more
      pronounced in pregnant women compared with non-pregnant women. The current
      results provide indication of modulation of cognitive-affective function during
      pregnancy. ERP alterations may suggest changes in the recruitment of neural
      resources to process emotional stimuli and alterations in attention allocation
      and evaluation of emotional stimuli among pregnant women. 

PMID- 24671066
TI  - Neuroscience and education: prime time to build the bridge.
AB  - As neuroscience gains social traction and entices media attention, the notion
      that education has much to benefit from brain research becomes increasingly
      popular. However, it has been argued that the fundamental bridge toward education
      is cognitive psychology, not neuroscience. We discuss four specific cases in
      which neuroscience synergizes with other disciplines to serve education, ranging
      from very general physiological aspects of human learning such as nutrition,
      exercise and sleep, to brain architectures that shape the way we acquire language
      and reading, and neuroscience tools that increasingly allow the early detection
      of cognitive deficits, especially in preverbal infants. Neuroscience methods,
      tools and theoretical frameworks have broadened our understanding of the mind in
      a way that is highly relevant to educational practice. Although the bridge's
      cement is still fresh, we argue why it is prime time to march over it. 

PMID- 24671068
TI  - Evidence of MAOA genotype involvement in spatial ability in males.
AB  - Although the monoamine oxidase-A (MAOA) gene has been linked to spatial learning
      and memory in animal models, convincing evidence in humans is lacking.
      Performance on an ecologically-valid, virtual computer-based equivalent of the
      Morris Water Maze task was compared between 28 healthy males with the low MAOA
      transcriptional activity and 41 healthy age- and IQ-matched males with the high
      MAOA transcriptional activity. The results revealed consistently better
      performance (reduced heading error, shorter path length, and reduced failed
      trials) for the high MAOA activity individuals relative to the low activity
      individuals. By comparison, groups did not differ on pre-task variables or
      strategic measures such as first-move latency. The results provide novel evidence
      of MAOA gene involvement in human spatial navigation using a virtual analogue of
      the Morris Water Maze task. 

PMID- 24671070
TI  - O(-) from amorphous and crystalline CO2 ices.
AB  - O(-) desorbed from amorphous and crystalline films of CO2 at 18 K under low
      energy electron impact is studied using time of flight mass spectrometry. The
      nature of the CO2 film is characterized by Fourier transform infrared
      spectrometry as a function of film thickness. It is found that the desorption
      rate from amorphous films is considerably larger than that from crystalline
      films. The desorption signal from the 4 eV resonance is found to be the dominant
      one as compared to that from the higher energy resonances, notably the one at 8
      eV observed in the gas phase. This is explained in terms of the large enhancement
      in the dissociative electron attachment cross section for the 4 eV resonance in
      the condensed phase reported earlier using the charge trapping method. 

PMID- 24671069
TI  - CRISPR/Cas9 mediated multiplex genome editing and heritable mutagenesis of BmKu70
      in Bombyx mori.
AB  - CRISPR/Cas9, a bacterial adaptive immune system derived genome-editing technique,
      has become to be one of the most compelling topics in biotechnology. Bombyx mori
      is an economically important insect and a model organism for studying
      lepidopteran and arthropod biology. Here we reported highly efficient and
      multiplex genome editing in B. mori cell line and heritable site-directed
      mutagenesis of Bmku70, which is required for NHEJ pathway and also related to
      antigen diversity, telomere length maintenance and subtelomeric gene silencing,
      using CRISPR/Cas9 system. We established a simple and practicable method and
      obtained several Bmku70 knockout B. mori lines, and showed that the frequency of
      HR was increased in embryos of the Bmku70 knockout B. mori. The mutant lines
      obtained in this study could be a candidate genetic resource for efficient knock
      in and fundamental research of DNA repair in B. mori. We also provided a strategy
      and procedure to perform heritable genome editing of target genes with no
      significant phenotype effect. 

PMID- 24671071
TI  - Association of folic acid supplementation during pregnancy and infant
      bronchiolitis.
AB  - Viral bronchiolitis affects 20%-30% of infants; because there is no known
      effective treatment, it is important to identify risk factors that contribute to
      its pathogenesis. Although adequate folate intake during the periconceptional
      period prevents neural tube defects, animal data suggest that higher
      supplementation may be a risk factor for child respiratory diseases. Using a
      population-based retrospective cohort of 167,333 women and infants, born in 1995
      2007 and enrolled in the Tennessee Medicaid program, we investigated the
      association between the filling of folic acid-containing prescriptions and infant
      bronchiolitis. We categorized women into the following 4 groups in relation to
      the first trimester: "none" (no prescription filled), "first trimester only,"
      "after first trimester," and "both" (prescriptions filled both during and after
      the first trimester). Overall, 21% of infants had a bronchiolitis diagnosis, and
      5% were hospitalized. Most women filled their first prescriptions after the fifth
      to sixth weeks of pregnancy, and most prescriptions contained 1,000 ug of folic
      acid. Compared with infants born to women in the "none" group, infants born to
      women in the "first trimester only" group had higher relative odds of
      bronchiolitis diagnosis (adjusted odds ratio = 1.17, 95% confidence interval:
      1.11, 1.22) and greater severity (adjusted odds ratio = 1.16, 95% confidence
      interval: 1.11, 1.22). This study's findings contribute to an understanding of
      the implications of prenatal nutritional supplement recommendations for infant
      bronchiolitis. 

PMID- 24671072
TI  - Accommodating measurements below a limit of detection: a novel application of Cox
      regression.
AB  - In environmental epidemiology, measurements of exposure biomarkers often fall
      below the assay's limit of detection. Existing methods for handling this problem,
      including deletion, substitution, parametric regression, and multiple imputation,
      can perform poorly if the proportion of "nondetects" is high or parametric models
      are mis-specified. We propose an approach that treats the measured analyte as the
      modeled outcome, implying a role reversal when the analyte is a putative cause of
      a health outcome. Following a scale reversal as well, our approach uses Cox
      regression to model the analyte, with confounder adjustment. The method makes
      full use of quantifiable analyte measures, while appropriately treating
      nondetects as censored. Under the proportional hazards assumption, the hazard
      ratio for a binary health outcome is interpretable as an adjusted odds ratio: the
      odds for the outcome at any particular analyte concentration divided by the odds
      given a lower concentration. Our approach is broadly applicable to cohort
      studies, case-control studies (frequency matched or not), and cross-sectional
      studies conducted to identify determinants of exposure. We illustrate the method
      with cross-sectional survey data to assess sex as a determinant of 2,3,7,8
      tetrachlorodibenzo-p-dioxin concentration and with prospective cohort data to
      assess the association between 2,4,4'-trichlorobiphenyl exposure and psychomotor
      development.

PMID- 24671073
TI  - The authors reply.

PMID- 24671078
TI  - Quantifying the tuberculosis disease burden in children.

PMID- 24671079
TI  - Importance of tuberculosis control to address child survival.

PMID- 24671081
TI  - Mutation in KANK2, encoding a sequestering protein for steroid receptor
      coactivators, causes keratoderma and woolly hair.
AB  - BACKGROUND: The combination of palmoplantar keratoderma and woolly hair is
      uncommon and reported as part of Naxos and Carvajal syndromes, both caused by
      mutations in desmosomal proteins and associated with cardiomyopathy. We describe
      two large consanguineous families with autosomal-recessive palmoplantar
      keratoderma and woolly hair, without cardiomyopathy and with no mutations in any
      known culprit gene. The aim of this study was to find the mutated gene in these
      families. METHODS AND RESULTS: Using whole-exome sequencing, we identified a
      homozygous missense c.2009C>T mutation in KANK2 in the patients (p.Ala670Val).
      KANK2 encodes the steroid receptor coactivator (SRC)-interacting protein (SIP),
      an ankyrin repeat containing protein, which sequesters SRCs in the cytoplasm and
      controls transcription activation of steroid receptors, among others, also of the
      vitamin D receptor (VDR). The mutation in KANK2 is predicted to abolish the
      sequestering abilities of SIP. Indeed, vitamin D-induced transactivation was
      increased in patient's keratinocytes. Furthermore, SRC-2 and SRC-3, coactivators
      of VDR and important components of epidermal differentiation, are localised to
      the nucleus of epidermal basal cells in patients, in contrast to the cytoplasmic
      distribution in the heterozygous control. CONCLUSIONS: These findings provide
      evidence that keratoderma and woolly hair can be caused by a non-desmosomal
      mechanism and further underline the importance of VDR for normal hair and skin
      phenotypes.

PMID- 24671080
TI  - Incidence of multidrug-resistant tuberculosis disease in children: systematic
      review and global estimates.
AB  - BACKGROUND: Multidrug-resistant tuberculosis threatens to reverse recent
      reductions in global tuberculosis incidence. Although children younger than 15
      years constitute more than 25% of the worldwide population, the global incidence
      of multidrug-resistant tuberculosis disease in children has never been
      quantified. We aimed to estimate the regional and global annual incidence of
      multidrug-resistant tuberculosis in children. METHODS: We developed two models:
      one to estimate the setting-specific risk of multidrug-resistant tuberculosis
      among child cases of tuberculosis, and a second to estimate the setting-specific
      incidence of tuberculosis disease in children. The model for risk of multidrug
      resistant tuberculosis among children with tuberculosis needed a systematic
      literature review. We multiplied the setting-specific estimates of multidrug
      resistant tuberculosis risk and tuberculosis incidence to estimate regional and
      global incidence of multidrug-resistant tuberculosis disease in children in 2010.
      FINDINGS: We identified 3403 papers, of which 97 studies met inclusion criteria
      for the systematic review of risk of multidrug-resistant tuberculosis. 31 studies
      reported the risk of multidrug-resistant tuberculosis in both children and
      treatment-naive adults with tuberculosis and were used for evaluation of the
      linear association between multidrug-resistant disease risk in these two patient
      groups. We identified that the setting-specific risk of multidrug-resistant
      tuberculosis was nearly identical in children and treatment-naive adults with
      tuberculosis, consistent with the assertion that multidrug-resistant disease in
      both groups reflects the local risk of transmitted multidrug-resistant
      tuberculosis. After application of these calculated risks, we estimated that
      around 999,792 (95% CI 937,877-1,055,414) children developed tuberculosis disease
      in 2010, of whom 31,948 (25,594-38,663) had multidrug-resistant disease.
      INTERPRETATION: Our estimates underscore that many cases of tuberculosis and
      multidrug-resistant tuberculosis disease are not being detected in children.
      Future estimates can be refined as more and better tuberculosis data and new
      diagnostic instruments become available. FUNDING: US National Institutes of
      Health, the Helmut Wolfgang Schumann Fellowship in Preventive Medicine at Harvard
      Medical School, the Norman E Zinberg Fellowship at Harvard Medical School, and
      the Doris and Howard Hiatt Residency in Global Health Equity and Internal
      Medicine at the Brigham and Women's Hospital.

PMID- 24671082
TI  - When the forest dies: the response of forest soil fungi to a bark beetle-induced
      tree dieback.
AB  - Coniferous forests cover extensive areas of the boreal and temperate zones. Owing
      to their primary production and C storage, they have an important role in the
      global carbon balance. Forest disturbances such as forest fires, windthrows or
      insect pest outbreaks have a substantial effect on the functioning of these
      ecosystems. Recent decades have seen an increase in the areas affected by
      disturbances in both North America and Europe, with indications that this
      increase is due to both local human activity and global climate change. Here we
      examine the structural and functional response of the litter and soil microbial
      community in a Picea abies forest to tree dieback following an invasion of the
      bark beetle Ips typographus, with a specific focus on the fungal community. The
      insect-induced disturbance rapidly and profoundly changed vegetation and nutrient
      availability by killing spruce trees so that the readily available root exudates
      were replaced by more recalcitrant, polymeric plant biomass components. Owing to
      the dramatic decrease in photosynthesis, the rate of decomposition processes in
      the ecosystem decreased as soon as the one-time litter input had been processed.
      The fungal community showed profound changes, including a decrease in biomass
      (2.5-fold in the litter and 12-fold in the soil) together with the disappearance
      of fungi symbiotic with tree roots and a relative increase in saprotrophic taxa.
      Within the latter group, successive changes reflected the changing availability
      of needle litter and woody debris. Bacterial biomass appeared to be either
      unaffected or increased after the disturbance, resulting in a substantial
      increase in the bacterial/fungal biomass ratio. 

PMID- 24671083
TI  - Phylogenetic and functional gene structure shifts of the oral microbiomes in
      periodontitis patients.
AB  - Determining the composition and function of subgingival dental plaque is crucial
      to understanding human periodontal health and disease, but it is challenging
      because of the complexity of the interactions between human microbiomes and human
      body. Here, we examined the phylogenetic and functional gene differences between
      periodontal and healthy individuals using MiSeq sequencing of 16S rRNA gene
      amplicons and a specific functional gene array (a combination of GeoChip 4.0 for
      biogeochemical processes and HuMiChip 1.0 for human microbiomes). Our analyses
      indicated that the phylogenetic and functional gene structure of the oral
      microbiomes were distinctly different between periodontal and healthy groups.
      Also, 16S rRNA gene sequencing analysis indicated that 39 genera were
      significantly different between healthy and periodontitis groups, and
      Fusobacterium, Porphyromonas, Treponema, Filifactor, Eubacterium, Tannerella,
      Hallella, Parvimonas, Peptostreptococcus and Catonella showed higher relative
      abundances in the periodontitis group. In addition, functional gene array data
      showed that a lower gene number but higher signal intensity of major genes
      existed in periodontitis, and a variety of genes involved in virulence factors,
      amino acid metabolism and glycosaminoglycan and pyrimidine degradation were
      enriched in periodontitis, suggesting their potential importance in periodontal
      pathogenesis. However, the genes involved in amino acid synthesis and pyrimidine
      synthesis exhibited a significantly lower relative abundance compared with
      healthy group. Overall, this study provides new insights into our understanding
      of phylogenetic and functional gene structure of subgingival microbial
      communities of periodontal patients and their importance in pathogenesis of
      periodontitis. 

PMID- 24671084
TI  - Elevated nitrate enriches microbial functional genes for potential bioremediation
      of complexly contaminated sediments.
AB  - Nitrate is an important nutrient and electron acceptor for microorganisms, having
      a key role in nitrogen (N) cycling and electron transfer in anoxic sediments.
      High-nitrate inputs into sediments could have a significant effect on N cycling
      and its associated microbial processes. However, few studies have been focused on
      the effect of nitrate addition on the functional diversity, composition,
      structure and dynamics of sediment microbial communities in contaminated aquatic
      ecosystems with persistent organic pollutants (POPs). Here we analyzed sediment
      microbial communities from a field-scale in situ bioremediation site, a creek in
      Pearl River Delta containing a variety of contaminants including polybrominated
      diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs), before and
      after nitrate injection using a comprehensive functional gene array (GeoChip
      4.0). Our results showed that the sediment microbial community functional
      composition and structure were markedly altered, and that functional genes
      involved in N-, carbon (C)-, sulfur (S)-and phosphorus (P)- cycling processes
      were highly enriched after nitrate injection, especially those microorganisms
      with diverse metabolic capabilities, leading to potential in situ bioremediation
      of the contaminated sediment, such as PBDE and PAH reduction/degradation. This
      study provides new insights into our understanding of sediment microbial
      community responses to nitrate addition, suggesting that indigenous
      microorganisms could be successfully stimulated for in situ bioremediation of
      POPs in contaminated sediments with nitrate addition. 

PMID- 24671085
TI  - Phages can constrain protist predation-driven attenuation of Pseudomonas
      aeruginosa virulence in multienemy communities.
AB  - The coincidental theory of virulence predicts that bacterial pathogenicity could
      be a by-product of selection by natural enemies in environmental reservoirs.
      However, current results are ambiguous and the simultaneous impact of multiple
      ubiquitous enemies, protists and phages on virulence evolution has not been
      investigated previously. Here we tested experimentally how Tetrahymena
      thermophila protist predation and PNM phage parasitism (bacteria-specific virus)
      alone and together affect the evolution of Pseudomonas aeruginosa PAO1 virulence,
      measured in wax moth larvae. Protist predation selected for small colony types,
      both in the absence and presence of phage, which showed decreased edibility to
      protists, reduced growth in the absence of enemies and attenuated virulence.
      Although phage selection alone did not affect the bacterial phenotype, it
      weakened protist-driven antipredatory defence (biofilm formation), its associated
      pleiotropic growth cost and the correlated reduction in virulence. These results
      suggest that protist selection can be a strong coincidental driver of attenuated
      bacterial virulence, and that phages can constrain this effect owing to effects
      on population dynamics and conflicting selection pressures. Attempting to define
      causal links such as these might help us to predict the cold and hot spots of
      coincidental virulence evolution on the basis of microbial community composition
      of environmental reservoirs. 

PMID- 24671086
TI  - Natural occurrence of microbial sulphur oxidation by long-range electron
      transport in the seafloor.
AB  - Recently, a novel mode of sulphur oxidation was described in marine sediments, in
      which sulphide oxidation in deeper anoxic layers was electrically coupled to
      oxygen reduction at the sediment surface. Subsequent experimental evidence
      identified that long filamentous bacteria belonging to the family
      Desulfobulbaceae likely mediated the electron transport across the centimetre
      scale distances. Such long-range electron transfer challenges some long-held
      views in microbial ecology and could have profound implications for sulphur
      cycling in marine sediments. But, so far, this process of electrogenic sulphur
      oxidation has been documented only in laboratory experiments and so its imprint
      on the seafloor remains unknown. Here we show that the geochemical signature of
      electrogenic sulphur oxidation occurs in a variety of coastal sediment
      environments, including a salt marsh, a seasonally hypoxic basin, and a subtidal
      coastal mud plain. In all cases, electrogenic sulphur oxidation was detected
      together with an abundance of Desulfobulbaceae filaments. Complementary
      laboratory experiments in intertidal sands demonstrated that mechanical
      disturbance by bioturbating fauna destroys the electrogenic sulphur oxidation
      signal. A survey of published geochemical data and 16S rRNA gene sequences
      identified that electrogenic sulphide oxidation is likely present in a variety of
      marine sediments with high sulphide generation and restricted bioturbation, such
      as mangrove swamps, aquaculture areas, seasonally hypoxic basins, cold sulphide
      seeps and possibly hydrothermal vent environments. This study shows for the first
      time that electrogenic sulphur oxidation occurs in a wide range of marine
      sediments and that bioturbation may exert a dominant control on its natural
      distribution. 

PMID- 24671087
TI  - Deciphering microbial landscapes of fish eggs to mitigate emerging diseases.
AB  - Animals and plants are increasingly suffering from diseases caused by fungi and
      oomycetes. These emerging pathogens are now recognized as a global threat to
      biodiversity and food security. Among oomycetes, Saprolegnia species cause
      significant declines in fish and amphibian populations. Fish eggs have an
      immature adaptive immune system and depend on nonspecific innate defences to ward
      off pathogens. Here, meta-taxonomic analyses revealed that Atlantic salmon eggs
      are home to diverse fungal, oomycete and bacterial communities. Although virulent
      Saprolegnia isolates were found in all salmon egg samples, a low incidence of
      Saprolegniosis was strongly correlated with a high richness and abundance of
      specific commensal Actinobacteria, with the genus Frondihabitans
      (Microbacteriaceae) effectively inhibiting attachment of Saprolegniato salmon
      eggs. These results highlight that fundamental insights into microbial landscapes
      of fish eggs may provide new sustainable means to mitigate emerging diseases. 

PMID- 24671088
TI  - Correlation between viral production and carbon mineralization under nitrate
      reducing conditions in aquifer sediment.
AB  - A variety of microbially mediated metabolic pathways impact biogeochemical
      cycling in terrestrial subsurface environments. However, the role that viruses
      have in influencing microbial mortality and microbial community structure is
      poorly understood. Here we investigated the production of viruses and change in
      microbial community structure within shallow alluvial aquifer sediment slurries
      amended with (13)C-labeled acetate and nitrate. Biostimulation resulted in
      production of viruses concurrent with acetate oxidation, (13)CO2 production and
      nitrate reduction. Interestingly, change in viral abundance was positively
      correlated to acetate consumption (r(2)=0.6252, P<0.05) and (13)CO2 production
      (r(2)=0.6572, P<0.05); whereas change in cell abundance was not correlated to
      acetate consumption or (13)CO2 production. Viral-mediated cell lysis has
      implications for microbial community structure. Betaproteobacteria predominated
      microbial community composition (62% of paired-end reads) upon inoculation but
      decreased in relative abundance and was negatively correlated to changes in viral
      abundance (r(2)=0.5036, P<0.05). As members of the Betaproteobacteria decreased,
      Gammaproteobacteria, specifically Pseudomonas spp., increased in relative
      abundance (82% of paired-end reads) and was positively correlated with the change
      in viral abundance (r(2)=0.5368, P<0.05). A nitrate-reducing bacterium,
      Pseudomonas sp. strain Alda10, was isolated from these sediments and produced
      viral-like particles with a filamentous morphology that did not result in cell
      lysis. Together, these results indicate that viruses are linked to carbon
      biogeochemistry and community structure in terrestrial subsurface sediments. The
      subsequent cell lysis has the potential to alter available carbon pools in
      subsurface environments, additionally controlling microbial community structure
      from the bottom-up. 

PMID- 24671089
TI  - Metabolomic analysis of diet-induced type 2 diabetes using UPLC/MS integrated
      with pattern recognition approach.
AB  - Metabolomics represents an emerging discipline concerned with comprehensive
      assessment of small molecule endogenous metabolites in biological systems and
      provides a powerful approach insight into the mechanisms of diseases. Type 2
      diabetes (T2D), called the burden of the 21st century, is growing with an
      epidemic rate. However, its precise molecular mechanism has not been
      comprehensively explored. In this study, we applied urinary metabolomics based on
      the UPLC/MS integrated with pattern recognition approaches to discover
      differentiating metabolites, to characterize and explore metabolic pathway
      disruption in an experimental model for high-fat-diet induced T2D. Six
      differentiating urinary metabolites were found in the negative mode, and two (2
      (4-hydroxy-3-methoxy-phenyl) acetaldehyde sulfate, 2-phenylethanol glucuronide)
      of which were identified involving the key metabolic pathways linked to pentose
      and glucuronate interconversions, starch, sucrose metabolism and tyrosine
      metabolism. Our study provides new insight into pathophysiologic mechanisms and
      may enhance the understanding of T2D pathogenesis. 

PMID- 24671092
TI  - Membrane lipid phase transition behavior of oocytes from three gorgonian corals
      in relation to chilling injury.
AB  - The lipid phase transition (LPT) from the fluid liquid crystalline phase to the
      more rigid gel structure phase that occurs upon exposure to low temperatures can
      affect physical structure and function of cellular membranes. This study set out
      to investigate the membrane phase behavior of oocytes of three gorgonian corals;
      Junceela fragilis, J. juncea and Ellisella robusta,at different developmental
      stages after exposure to reduced temperatures. Oocytes were chilled to 5 degrees
      C for 48, 96 or 144 h, and the LPT temperature (LPTT) was determined with Fourier
      Transform Infrared (FTIR) spectroscopy. The J. fragilis oocytes had a higher LPTT
      (~23.0-23.7 degrees C) than those of J. juncea and E. robusta oocytes
      (approximately 18.3-20.3 degrees C). Upon chilling for 96 h at 5 degrees C, the
      LPTTs of J. juncea and E. robusta oocytes in the early (18.0+/-1.0 and 18.3+/-0.6
      degrees C, respectively) and late (17.3+/-0.6 and 17.7+/-1.2 degrees C,
      respectively) stages were significantly lower than those of J. fragilis oocytes
      (20.3+/-2.1 and 19.3+/-1.5 degrees C for the early and late stages,
      respectively). The LPTTs of early stage gorgonian oocytes was significantly lower
      than those of late stage oocytes. These results suggest that the LPT of three
      gorgonian oocytes at different developmental stages may have been influenced by
      the phospholipid composition of their plasma membranes, which could have
      implications for their low temperature resistance. 

PMID- 24671091
TI  - F9 fimbriae of uropathogenic Escherichia coli are expressed at low temperature
      and recognise Galbeta1-3GlcNAc-containing glycans.
AB  - Uropathogenic Escherichia coli (UPEC) is the leading causative agent of urinary
      tract infections (UTI) in the developed world. Among the major virulence factors
      of UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC
      strains typically possess a range of adhesins, with type 1 fimbriae and P
      fimbriae of the chaperone-usher class the best characterised. We previously
      identified and characterised F9 as a new chaperone-usher fimbrial type that
      mediates biofilm formation. However, the regulation and specific role of F9
      fimbriae remained to be determined in the context of wild-type clinical UPEC
      strains. In this study we have assessed the distribution and genetic context of
      the f9 operon among diverse E. coli lineages and pathotypes and demonstrated that
      f9 genes are significantly more conserved in a UPEC strain collection in
      comparison to the well-defined E. coli reference (ECOR) collection. In the
      prototypic UPEC strain CFT073, the global regulator protein H-NS was identified
      as a transcriptional repressor of f9 gene expression at 37 degrees C through its
      ability to bind directly to the f9 promoter region. F9 fimbriae expression was
      demonstrated at 20 degrees C, representing the first evidence of functional F9
      fimbriae expression by wild-type E. coli. Finally, glycan array analysis
      demonstrated that F9 fimbriae recognise and bind to terminal Galbeta1-3GlcNAc
      structures. 

PMID- 24671090
TI  - Natural history of cone disease in the murine model of Leber congenital amaurosis
      due to CEP290 mutation: determining the timing and expectation of therapy.
AB  - BACKGROUND: Mutations in the CEP290 (cilia-centrosomal protein 290 kDa) gene in
      Leber congenital amaurosis (LCA) cause early onset visual loss but retained cone
      photoreceptors in the fovea, which is the potential therapeutic target. A cone
      only mouse model carrying a Cep290 gene mutation, rd16;Nrl-/-, was engineered to
      mimic the human disease. In the current study, we determined the natural history
      of retinal structure and function in this murine model to permit design of pre
      clinical proof-of-concept studies and allow progress to be made toward human
      therapy. Analyses of retinal structure and visual function in CEP290-LCA patients
      were also performed for comparison with the results in the model. METHODS:
      Rd16;Nrl-/- mice were studied in the first 90 days of life with optical coherence
      tomography (OCT), electroretinography (ERG), retinal histopathology and
      immunocytochemistry. Structure and function data from a cohort of patients with
      CEP290-LCA (n = 15; ages 7-48) were compared with those of the model. RESULTS:
      CEP290-LCA patients retain a central island of photoreceptors with normal
      thickness at the fovea (despite severe visual loss); the extent of this island
      declined slowly with age. The rd16;Nrl-/- model also showed a relatively slow
      photoreceptor layer decline in thickness with ~80% remaining at 3 months. The
      number of pseudorosettes also became reduced. By comparison to single mutant Nrl
      /- mice, UV- and M-cone ERGs of rd16;Nrl-/- were at least 1 log unit reduced at 1
      month of age and declined further over the 3 months of monitoring. Expression of
      GNAT2 and S-opsin also decreased with age. CONCLUSIONS: The natural history of
      early loss of photoreceptor function with retained cone cell nuclei is common to
      both CEP290-LCA patients and the rd16;Nrl-/- murine model. Pre-clinical proof-of
      concept studies for uniocular therapies would seem most appropriate to begin with
      intervention at P35-40 and re-study after one month by assaying interocular
      difference in the UV-cone ERG.

PMID- 24671094
TI  - A novel approach for food intake detection using electroglottography.
AB  - Many methods for monitoring diet and food intake rely on subjects self-reporting
      their daily intake. These methods are subjective, potentially inaccurate and need
      to be replaced by more accurate and objective methods. This paper presents a
      novel approach that uses an electroglottograph (EGG) device for an objective and
      automatic detection of food intake. Thirty subjects participated in a four-visit
      experiment involving the consumption of meals with self-selected content.
      Variations in the electrical impedance across the larynx caused by the passage of
      food during swallowing were captured by the EGG device. To compare performance of
      the proposed method with a well-established acoustical method, a throat
      microphone was used for monitoring swallowing sounds. Both signals were segmented
      into non-overlapping epochs of 30 s and processed to extract wavelet features.
      Subject-independent classifiers were trained, using artificial neural networks,
      to identify periods of food intake from the wavelet features. Results from leave
      one-out cross validation showed an average per-epoch classification accuracy of
      90.1% for the EGG-based method and 83.1% for the acoustic-based method,
      demonstrating the feasibility of using an EGG for food intake detection. 

PMID- 24671093
TI  - Probenecid blocks human P2X7 receptor-induced dye uptake via a pannexin-1
      independent mechanism.
AB  - P2X7 is a ligand-gated ion channel which is activated by ATP and displays
      secondary permeability characteristics. The mechanism of development of the
      secondary permeability pathway is currently unclear, although a role for the
      hemichannel protein pannexin-1 has been suggested. In this study we investigated
      the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1beta
      secretion from human monocytes. We found no pharmacological evidence for
      involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293
      cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic
      inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7
      induced cationic and anionic dye uptake in stably transfected human P2X7 HEK-293
      cells. An IC50 value of 203 MUM was calculated for blockade of ATP-induced
      responses at human P2X7. Probenecid also reduced dye uptake and IL-1beta
      secretion from human CD14+ monocytes whereas carbenoxolone and 10Panx1 showed no
      inhibitory effect. Patch clamp and calcium indicator experiments revealed that
      probenecid directly blocks the human P2X7 receptor. 

PMID- 24671095
TI  - Metabolic syndrome increases risk of Barrett esophagus in the absence of
      gastroesophageal reflux: an analysis of SEER-Medicare Data.
AB  - GOALS: To evaluate the association between metabolic syndrome (MetS) and risk of
      Barrett esophagus (BE) using the Surveillance, Epidemiology, and End Results
      (SEER)-Medicare linked database compared with 2 control groups--Medicare
      population controls and endoscopy controls. BACKGROUND: BE principally arises as
      an adaptation to the proinflammatory state induced by gastroesophageal reflux
      disease (GERD). The relationship between obesity and BE is presumed to be
      mediated by GERD. However, evidence suggests central adiposity also increases
      risk of BE independent of GERD. Central adiposity is one risk factor defining
      MetS, which confers a systemic proinflammatory state--a potential GERD
      independent mechanism by which obesity could increase the risk of BE. STUDY: MetS
      was defined as diagnosis of at least 3 of the following conditions: obesity,
      elevated triglycerides, high blood pressure, and elevated fasting glucose.
      Multivariable logistic regression was used to estimate adjusted odds ratios and
      95% confidence intervals. RESULTS: In 2198 incident BE cases, prior MetS was
      significantly associated with BE (odds ratio, 1.20; 95% confidence interval:
      1.07, 1.36) compared with population controls. However, GERD status modified the
      association; among those without prior GERD, MetS increased risk of BE by 34%;
      however, no association was observed among those with a prior GERD diagnosis (P
      value for effect modification <0.001). MetS was not associated with risk of BE
      compared with endoscopy controls. CONCLUSIONS: MetS increased the risk of BE
      compared with population controls, an association driven by and confined to the
      non-GERD stratum. MetS may mediate an association between central adiposity and
      BE for those without GERD.

PMID- 24671097
TI  - Operative volume in colon surgery: a matched cohort analysis.
AB  - Although previous studies have suggested that higher volumes of colectomies
      performed by surgeons and hospitals are associated with lower mortality, less is
      known about the relationship between volume and resource utilization. The
      research team tested the association between volume, costs, complications, length
      of stay, and mortality using data from the National Inpatient Sample. Results
      suggest higher volumes for both surgeons and hospitals were associated with lower
      costs, fewer complications, shorter length of stay, and lower mortality.
      Propensity score matching showed no significant difference in mortality by
      surgeon volume (7.38% vs 7.46%, P=.0.842), but significantly fewer complications
      (45.06% vs 49.10%, P=.008), shorter length of stay (11.8 vs 13.1 days, P<.0001),
      and lower costs ($33,142 vs $29,578, P<.0001) for high-volume surgeons. Although
      the major driver of complications and mortality is burden of disease and comorbid
      conditions, individual surgeon volume is an important determinant of length of
      stay and costs.

PMID- 24671096
TI  - Wnt11 is required for oriented migration of dermogenic progenitor cells from the
      dorsomedial lip of the avian dermomyotome.
AB  - The embryonic origin of the dermis in vertebrates can be traced back to the
      dermomyotome of the somites, the lateral plate mesoderm and the neural crest. The
      dermal precursors directly overlying the neural tube display a unique dense
      arrangement and are the first to induce skin appendage formation in vertebrate
      embryos. These dermal precursor cells have been shown to derive from the
      dorsomedial lip of the dermomyotome (DML). Based on its expression pattern in the
      DML, Wnt11 is a candidate regulator of dorsal dermis formation. Using EGFP-based
      cell labelling and time-lapse imaging, we show that the Wnt11 expressing DML is
      the source of the dense dorsal dermis. Loss-of-function studies in chicken
      embryos show that Wnt11 is indeed essential for the formation of dense dermis
      competent to support cutaneous appendage formation. Our findings show that
      dermogenic progenitors cannot leave the DML to form dense dorsal dermis following
      Wnt11 silencing. No alterations were noticeable in the patterning or in the
      epithelial state of the dermomyotome including the DML. Furthermore, we show that
      Wnt11 expression is regulated in a manner similar to the previously described
      early dermal marker cDermo-1. The analysis of Wnt11 mutant mice exhibits an
      underdeveloped dorsal dermis and strongly supports our gene silencing data in
      chicken embryos. We conclude that Wnt11 is required for dense dermis and
      subsequent cutaneous appendage formation, by influencing the cell fate decision
      of the cells in the DML. 

PMID- 24671098
TI  - The human side of lean teams.
AB  - Organizations use lean principles to increase quality and decrease costs. Lean
      projects require an understanding of systems-wide processes and utilize
      interdisciplinary teams. Most lean tools are straightforward, and the biggest
      barrier to successful implementation is often development of the team aspect of
      the lean approach. The purpose of this article is to share challenges experienced
      by a lean team charged with improving a hospital discharge process. Reflection on
      the experience provides an opportunity to highlight lessons from The Team
      Handbook by Peter Scholtes and colleagues. To improve the likelihood that process
      improvement initiatives, including lean projects, will be successful,
      organizations should consider providing training in organizational change
      principles and team building. The authors' lean team learned these lessons the
      hard way. Despite the challenges, the team successfully implemented changes
      throughout the organization that have had a positive impact. Training to
      understand the psychology of change might have decreased the resistance faced in
      implementing these changes. 

PMID- 24671099
TI  - The quality of reporting methods and results in network meta-analyses: an
      overview of reviews and suggestions for improvement.
AB  - INTRODUCTION: Some have suggested the quality of reporting of network meta
      analyses (a technique used to synthesize information to compare multiple
      interventions) is sub-optimal. We sought to review information addressing this
      claim. OBJECTIVE: To conduct an overview of existing evaluations of quality of
      reporting in network meta-analyses and indirect treatment comparisons, and to
      compile a list of topics which may require detailed reporting guidance to enhance
      future reporting quality. METHODS: An electronic search of Medline and the
      Cochrane Registry of methodologic studies (January 2004-August 2013) was
      performed by an information specialist. Studies describing findings from quality
      of reporting assessments were sought. Screening of abstracts and full texts was
      performed by two team members. Descriptors related to all aspects of reporting a
      network meta-analysis were summarized. RESULTS: We included eight reports
      exploring the quality of reporting of network meta-analyses. From past reviews,
      authors found several aspects of network meta-analyses were inadequately
      reported, including primary information about literature searching, study
      selection, and risk of bias evaluations; statement of the underlying assumptions
      for network meta-analysis, as well as efforts to verify their validity; details
      of statistical models used for analyses (including information for both Bayesian
      and Frequentist approaches); completeness of reporting of findings; and
      approaches for summarizing probability measures as additional important
      considerations. CONCLUSIONS: While few studies were identified, several
      deficiencies in the current reporting of network meta-analyses were observed.
      These findings reinforce the need to develop reporting guidance for network meta
      analyses. Findings from this review will be used to guide next steps in the
      development of reporting guidance for network meta-analysis in the format of an
      extension of the PRISMA (Preferred Reporting Items for Systematic reviews and
      Meta-Analysis) Statement.

PMID- 24671100
TI  - Effect of osmotic stress on the expression of TRPV4 and BKCa channels and
      possible interaction with ERK1/2 and p38 in cultured equine chondrocytes.
AB  - The metabolic activity of articular chondrocytes is influenced by osmotic
      alterations that occur in articular cartilage secondary to mechanical load. The
      mechanisms that sense and transduce mechanical signals from cell swelling and
      initiate volume regulation are poorly understood. The purpose of this study was
      to investigate how the expression of two putative osmolyte channels [transient
      receptor potential vanilloid 4 (TRPV4) and large-conductance Ca(2+)-activated
      K(+) (BKCa)] in chondrocytes is modulated in different osmotic conditions and to
      examine a potential role for MAPKs in this process. Isolated equine articular
      chondrocytes were subjected to anisosmotic conditions, and TRPV4 and BKCa channel
      expression and ERK1/2 and p38 MAPK protein phosphorylation were investigated
      using Western blotting. Results indicate that the TRPV4 channel contributes to
      the early stages of hypo-osmotic stress, while the BKCa channel is involved in
      responding to elevated intracellular Ca(2+) and mediating regulatory volume
      decrease. ERK1/2 is phosphorylated by hypo-osmotic stress (P < 0.001), and p38
      MAPK is phosphorylated by hyperosmotic stress (P < 0.001). In addition, this
      study demonstrates the importance of endogenous ERK1/2 phosphorylation in TRPV4
      channel expression, where blocking ERK1/2 by a specific inhibitor (PD98059)
      prevented increased levels of the TRPV4 channel in cells exposed to hypo-osmotic
      stress and decreased TRPV4 channel expression to below control levels in iso
      osmotic conditions (P < 0.001). 

PMID- 24671101
TI  - Hypoxia-induced changes in Ca(2+) mobilization and protein phosphorylation
      implicated in impaired wound healing.
AB  - The process of wound healing must be tightly regulated to achieve successful
      restoration of injured tissue. Previously, we demonstrated that when corneal
      epithelium is injured, nucleotides and neuronal factors are released to the
      extracellular milieu, generating a Ca(2+) wave from the origin of the wound to
      neighboring cells. In the present study we sought to determine how the
      communication between epithelial cells in the presence or absence of neuronal
      wound media is affected by hypoxia. A signal-sorting algorithm was developed to
      determine the dynamics of Ca(2+) signaling between neuronal and epithelial cells.
      The cross talk between activated corneal epithelial cells in response to neuronal
      wound media demonstrated that injury-induced Ca(2+) dynamic patterns were altered
      in response to decreased O2 levels. These alterations were associated with an
      overall decrease in ATP and changes in purinergic receptor-mediated Ca(2+)
      mobilization and localization of N-methyl-d-aspartate receptors. In addition, we
      used the cornea in an organ culture wound model to examine how hypoxia impedes
      reepithelialization after injury. There was a change in the recruitment of
      paxillin to the cell membrane and deposition of fibronectin along the basal
      lamina, both factors in cell migration. Our results provide evidence that complex
      Ca(2+)-mediated signaling occurs between sensory neurons and epithelial cells
      after injury and is critical to wound healing. Information revealed by these
      studies will contribute to an enhanced understanding of wound repair under
      compromised conditions and provide insight into ways to effectively stimulate
      proper epithelial repair.

PMID- 24671102
TI  - Effects of Huanglian-Jie-Du-Tang and its modified formula on the modulation of
      amyloid-beta precursor protein processing in Alzheimer's disease models.
AB  - Huanglian-Jie-Du-Tang (HLJDT) is a famous traditional Chinese herbal formula that
      has been widely used clinically to treat cerebral ischemia. Recently, we found
      that berberine, a major alkaloid compound in HLJDT, reduced amyloid-beta (Abeta)
      accumulation in an Alzheimer's disease (AD) mouse model. In this study, we
      compared the effects of HLJDT, four single component herbs of HLJDT (Rhizoma
      coptidis (RC), Radix scutellariae (RS), Cortex phellodendri (CP) and Fructus
      gardenia (FG)) and the modified formula of HLJDT (HLJDT-M, which is free of RS)
      on the regulatory processing of amyloid-beta precursor protein (APP) in an in
      vitro model of AD. Here we show that treatment with HLJDT-M and its components
      RC, CP, and the main compound berberine on N2a mouse neuroblastoma cells stably
      expressing human APP with the Swedish mutation (N2a-SwedAPP) significantly
      decreased the levels of full-length APP, phosphorylated APP at threonine 668, C
      terminal fragments of APP, soluble APP (sAPP)-alpha and sAPPbeta-Swedish and
      reduced the generation of Abeta peptide in the cell lysates of N2a-SwedAPP. HLJDT
      M showed more significant APP- and Abeta- reducing effects than berberine, RC or
      CP treatment alone. In contrast, HLJDT, its component RS and the main active
      compound of RS, baicalein, strongly increased the levels of all the metabolic
      products of APP in the cell lysates. The extract from FG, however, did not
      influence APP modulation. Interestingly, regular treatment of TgCRND8 APP
      transgenic mice with baicalein exacerbated the amyloid plaque burden, APP
      metabolism and Abeta production. Taken together, these data provide convincing
      evidence that HLJDT and baicalein treatment can increase the amyloidogenic
      metabolism of APP which is at least partly responsible for the baicalein-mediated
      Abeta plaque increase in the brains of TgCRND8 mice. On the other hand, HLJDT-M
      significantly decreased all the APP metabolic products including Abeta. Further
      study of HLJDT-M for therapeutic use in treating AD is warranted. 

PMID- 24671103
TI  - The effect of medical marijuana laws on crime: evidence from state panel data,
      1990-2006.
AB  - BACKGROUND: Debate has surrounded the legalization of marijuana for medical
      purposes for decades. Some have argued medical marijuana legalization (MML) poses
      a threat to public health and safety, perhaps also affecting crime rates. In
      recent years, some U.S. states have legalized marijuana for medical purposes,
      reigniting political and public interest in the impact of marijuana legalization
      on a range of outcomes. METHODS: Relying on U.S. state panel data, we analyzed
      the association between state MML and state crime rates for all Part I offenses
      collected by the FBI. FINDINGS: Results did not indicate a crime exacerbating
      effect of MML on any of the Part I offenses. Alternatively, state MML may be
      correlated with a reduction in homicide and assault rates, net of other
      covariates. CONCLUSIONS: These findings run counter to arguments suggesting the
      legalization of marijuana for medical purposes poses a danger to public health in
      terms of exposure to violent crime and property crimes.

PMID- 24671105
TI  - Sequential acquisition of multi-dimensional heteronuclear chemical shift
      correlation spectra with 1H detection.
AB  - RF pulse schemes for the simultaneous acquisition of heteronuclear multi
      dimensional chemical shift correlation spectra, such as {HA(CA)NH & HA(CACO)NH},
      {HA(CA)NH & H(N)CAHA} and {H(N)CAHA & H(CC)NH}, that are commonly employed in the
      study of moderately-sized protein molecules, have been implemented using dual
      sequential (1)H acquisitions in the direct dimension. Such an approach is not
      only beneficial in terms of the reduction of experimental time as compared to
      data collection via two separate experiments but also facilitates the unambiguous
      sequential linking of the backbone amino acid residues. The potential of
      sequential (1)H data acquisition procedure in the study of RNA is also
      demonstrated here. 

PMID- 24671104
TI  - Longitudinal association between body mass index and health-related quality of
      life.
AB  - OBJECTIVE: Health-related quality of life (HRQoL) is an important outcome in
      individuals with a high risk for cardiovascular diseases. We investigated the
      association of HRQoL and body mass index (BMI) as an indicator for obesity.
      DESIGN: Secondary longitudinal analysis of the ORBITAL study, an intervention
      study which included high-risk cardiovascular primary care patients with
      hypercholesterolemia and an indication for statin therapy. METHODS: HRQoL was
      determined with the generic Short Form (SF)-12 health status instrument. Body
      weight and height were assessed at baseline and at months 6, 12, 18, 24, 30, and
      36. We used a linear and a linear mixed-effects regression model to investigate
      the association between BMI and SF-12 summary scores at baseline as well as
      between change in BMI and SF-12 summary scores over 3 years. We adjusted for age,
      sex, smoking status, and in the longitudinal analysis also for the study arm and
      its interaction term with time. RESULTS: Of the 7640 participants who completed
      the baseline questionnaire, 6726 participants (mean age: 61 years) were analyzed.
      The baseline BMI was inversely associated with physical and mental SF-12 summary
      scores (beta [95% CI] per 1 kg/m2: -0.36 [-0.41; -0.30] and -0.05 [-0.11; -0.00],
      respectively). A significant association between the change in BMI and physical
      SF-12 summary scores over time was only present in women (-0.18 [-0.27; -0.09])
      and only in obese participants (-0.19 [-0.29; -0.10]). A change in BMI was
      directly associated with mental SF-12 summary scores (0.12 [0.06; 0.19]) in the
      total population. CONCLUSION: Increases in BMI were associated with decreases in
      physical HRQoL, particularly in obese individuals and in women. In contrast, the
      mental HRQoL seemed to increase with increasing BMI over time. Thus, body weight
      management with respect to the HRQoL should be evaluated differentially by sex
      and body weight status. TRIAL REGISTRATION: ClinicalTrials.gov NCT00379249.

PMID- 24671106
TI  - L-serine treatment may improve neurorestoration of rats after permanent focal
      cerebral ischemia potentially through improvement of neurorepair.
AB  - The present study was conducted to clarify whether treatment with L-serine can
      improve the brain repair and neurorestoration of rats after permanent middle
      cerebral artery occlusion (pMCAO). After pMCAO, the neurological functions, brain
      lesion volume, and cortical injury were determined. GDNF, NGF, NCAM L1, tenascin
      C, and Nogo-A levels were measured. Proliferation and differentiation of the
      neural stem cells (NSCs) and proliferation of the microvessels in the ischemic
      boundary zone of the cortex were evaluated. Treatment with L-serine (168 mg/kg
      body weight, i.p.) began 3 h after pMCAO and was repeated every 12 h for 7 days
      or until the end of the experiment. L-Serine treatment: 1) reduced the lesion
      volume and neuronal loss; 2) improved the recovery of neurological functions; 3)
      elevated the expression of nerve growth-related factors; and 4) facilitated the
      proliferation of endogenous NSCs and microvessels activated after pMCAO and
      increased the number of new-born neurons. 5) D-cycloserine, an inhibitor of
      serine hydroxymethyltransferase, blunted the effects of L-serine on NSC
      proliferation, differentiation, microvascular proliferation. In conclusions, L
      serine treatment in pMCAO rats can reduce brain injury and facilitate
      neurorestoration which is partly associated with the improvement of proliferation
      of NSCs and microvessels, reconstruction of neurovascular units and resultant
      neurorepair. The effects of L-serine on endogenous NSC proliferation and
      microvascular proliferation are partly mediated by the action of L-serine as a
      substrate for the production of one-carbon groups used for purine and pyrimidine
      synthesis and modulation of the expression of some nerve growth-related factors. 

PMID- 24671108
TI  - Foraging responses of black-legged kittiwakes to prolonged food-shortages around
      colonies on the Bering Sea shelf.
AB  - We hypothesized that changes in southeastern Bering Sea foraging conditions for
      black-legged kittiwakes (Rissa tridactyla) have caused shifts in habitat use with
      direct implications for population trends. To test this, we compared at-sea
      distribution, breeding performance, and nutritional stress of kittiwakes in three
      years (2008-2010) at two sites in the Pribilof Islands, where the population has
      either declined (St. Paul) or remained stable (St. George). Foraging conditions
      were assessed from changes in (1) bird diets, (2) the biomass and distribution of
      juvenile pollock (Theragra chalcogramma) in 2008 and 2009, and (3) eddy kinetic
      energy (EKE; considered to be a proxy for oceanic prey availability). In years
      when biomass of juvenile pollock was low and patchily distributed in shelf
      regions, kittiwake diets included little or no neritic prey and a much higher
      occurrence of oceanic prey (e.g. myctophids). Birds from both islands foraged on
      the nearby shelves, or made substantially longer-distance trips overnight to the
      basin. Here, feeding was more nocturnal and crepuscular than on the shelf, and
      often occurred near anticyclonic, or inside cyclonic eddies. As expected from
      colony location, birds from St. Paul used neritic waters more frequently, whereas
      birds from St. George typically foraged in oceanic waters. Despite these
      distinctive foraging patterns, there were no significant differences between
      colonies in chick feeding rates or fledging success. High EKE in 2010 coincided
      with a 63% increase in use of the basin by birds from St. Paul compared with 2008
      when EKE was low. Nonetheless, adult nutritional stress, which was relatively
      high across years at both colonies, peaked in birds from St. Paul in 2010.
      Diminishing food resources in nearby shelf habitats may have contributed to
      kittiwake population declines at St Paul, possibly driven by increased adult
      mortality or breeding desertion due to high foraging effort and nutritional
      stress. 

PMID- 24671107
TI  - Beta-actin deficiency with oxidative posttranslational modifications in Rett
      syndrome erythrocytes: insights into an altered cytoskeletal organization.
AB  - Beta-actin, a critical player in cellular functions ranging from cell motility
      and the maintenance of cell shape to transcription regulation, was evaluated in
      the erythrocyte membranes from patients with typical Rett syndrome (RTT) and
      methyl CpG binding protein 2 (MECP2) gene mutations. RTT, affecting almost
      exclusively females with an average frequency of 1?10,000 female live births, is
      considered the second commonest cause of severe cognitive impairment in the
      female gender. Evaluation of beta-actin was carried out in a comparative cohort
      study on red blood cells (RBCs), drawn from healthy control subjects and RTT
      patients using mass spectrometry-based quantitative analysis. We observed a
      decreased expression of the beta-actin isoforms (relative fold changes for spots
      1, 2 and 3: -1.82+/-0.15, -2.15+/-0.06, and -2.59+/-0.48, respectively) in
      pathological RBCs. The results were validated by western blotting and
      immunofluorescence microscopy. In addition, beta-actin from RTT patients also
      showed a dramatic increase in oxidative posttranslational modifications (PTMs) as
      the result of its binding with the lipid peroxidation product 4-hydroxy-2-nonenal
      (4-HNE). Our findings demonstrate, for the first time, a beta-actin down
      regulation and oxidative PTMs for RBCs of RTT patients, thus indicating an
      altered cytoskeletal organization. 

PMID- 24671109
TI  - DNA compaction induced by a cationic polymer or surfactant impact gene expression
      and DNA degradation.
AB  - There is an increasing interest in achieving gene regulation in biotechnological
      and biomedical applications by using synthetic DNA-binding agents. Most studies
      have so far focused on synthetic sequence-specific DNA-binding agents. Such
      approaches are relatively complicated and cost intensive and their level of
      sophistication is not always required, in particular for biotechnological
      application. Our study is inspired by in vivo data that suggest that DNA
      compaction might contribute to gene regulation. This study exploits the potential
      of using synthetic DNA compacting agents that are not sequence-specific to
      achieve gene regulation for in vitro systems. The semi-synthetic in vitro system
      we use include common cationic DNA-compacting agents, poly(amido amine) (PAMAM)
      dendrimers and the surfactant hexadecyltrimethylammonium bromide (CTAB), which we
      apply to linearized plasmid DNA encoding for the luciferase reporter gene. We
      show that complexing the DNA with either of the cationic agents leads to gene
      expression inhibition in a manner that depends on the extent of compaction. This
      is demonstrated by using a coupled in vitro transcription-translation system. We
      show that compaction can also protect DNA against degradation in a dose-dependent
      manner. Furthermore, our study shows that these effects are reversible and DNA
      can be released from the complexes. Release of DNA leads to restoration of gene
      expression and makes the DNA susceptible to degradation by Dnase. A highly
      charged polyelectrolyte, heparin, is needed to release DNA from dendrimers, while
      DNA complexed with CTAB dissociates with the non-ionic surfactant C12E5. Our
      results demonstrate the relation between DNA compaction by non-specific DNA
      binding agents and gene expression and gene regulation can be achieved in vitro
      systems in a reliable dose-dependent and reversible manner. 

PMID- 24671110
TI  - Predicting coronary heart disease using risk factor categories for a Japanese
      urban population, and comparison with the framingham risk score: the suita study.
AB  - AIM: The Framingham risk score (FRS) is one of the standard tools used to predict
      the incidence of coronary heart disease (CHD). No previous study has investigated
      its efficacy for a Japanese population cohort. The purpose of this study was to
      develop new coronary prediction algorithms for the Japanese population in the
      manner of the FRS, and to compare them with the original FRS. METHODS: Our
      coronary prediction algorithms for Japanese were based on a large population
      based cohort study (Suita study). The study population comprised 5,521 healthy
      Japanese. They were followed-up for 11.8 years on average, and 213 cases of CHD
      were observed. Multiple Cox proportional hazard model by stepwise selection was
      used to construct the prediction model. RESULTS: Our coronary prediction
      algorithms for Japanese patients were based on a large populationbased cohort
      study (the Suita study). A multiple Cox proportional hazard model by stepwise
      selection was used to construct the prediction model. The C-statistics showed
      that the new model had better accuracy than the original and recalibrated
      Framingham scores. The net reclassification improvement (NRI) by the Suita score
      with the inclusion of CKD was 41.2% (P<0.001) compared with the original FRS. The
      recalibration of the FRS slightly improved the efficiency of the prediction, but
      it was still worse than the Suita score with the CKD model. The calibration
      analysis suggested that the original FRS and the recalibrated FRS overestimated
      the risk of CHD in the Japanese population. The Suita score with CKD more
      accurately predicted the risk of CHD. CONCLUSION: The FRS and recalibrated FRS
      overestimated the 10-year risk of CHD for the Japanese population. A predictive
      score including CKD as a coronary risk factor for the Japanese population was
      more accurate for predicting CHD than the original Framingham risk scores in
      terms of the C-statics and NRI.

PMID- 24671111
TI  - The values of wall shear stress, turbulence kinetic energy and blood pressure
      gradient are associated with atherosclerotic plaque erosion in rabbits.
AB  - AIM: To clarify the contribution of hemodynamic factors to the onset of plaque
      erosion in smooth muscle cell (SMC)-rich atherosclerotic plaque. METHODS: We
      developed a rabbit model of SMC-rich atherosclerotic plaque with various degree
      of stenosis induced by incomplete ligation and generated three-dimensional models
      of five rabbit femoral arteries based on 130-162 serial histological cross
      sections at 100-MUm intervals per artery. We performed a computational blood flow
      simulation using the Reynolds-averaged Navier-Stokes model and calculated the
      wall shear stress (WSS), turbulence kinetic energy (TKE), blood pressure (BP) and
      blood pressure gradients (BPG) in eight sections (the inlet, the stenotic portion
      and areas 1, 2 and 5mm from the stenotic portion) in each rabbit. We also
      investigated whether the magnitude of WSS or TKE was related to the presence or
      absence of erosive injury by evaluating six points (the locally highest, median
      and lowest of WSS or TKE) in each section. RESULTS: The magnitudes of WSS, TKE
      and BPG, but not BP, correlated significantly with the extent of histologically
      defined plaque erosion (WSS, r=0.55, p<0.001; TKE, r=0.53, p<0.001; BPG, r=0.61,
      p<0.0001, n=40). The values for WSS and TKE were significantly larger at sites
      with, compared to without, erosive injury (n=107 and n=119 points, respectively;
      both p<0.0001). CONCLUSIONS: These results suggest that increased values of WSS,
      TKE and BPG considerably contribute to the onset of plaque erosion.

PMID- 24671112
TI  - ES-62, a therapeutic anti-inflammatory agent evolved by the filarial nematode
      Acanthocheilonema viteae.
AB  - Filarial nematodes cause long-term infections in hundreds of millions of people.
      A significant proportion of those affected develop a number of debilitating
      health problems but, remarkably, such infections are often unnoticed for many
      years. It is well known that parasitic worms modulate, yet do not completely
      inhibit, host immunological pathways, promoting their survival by limiting
      effective immune mechanisms. Such immunoregulation largely depends on molecules
      released by the worms, termed excretory-secretory products (ES). One of these
      products is the molecule ES-62, which is actively secreted by the rodent filarial
      nematode Acanthocheilonema viteae. ES-62 has been shown to exert anti
      inflammatory actions thorough its phosphorylcholine (PC)-containing moiety on a
      variety of cells of the immune system, affecting intracellular signalling
      pathways associated with antigen receptor- and TLR-dependent responses. We
      summarise here how ES-62 modulates key signal transduction elements and how such
      immunomodulation confers protection to mice subjected to certain experimental
      models of inflammatory disease. Finally, we discuss recent results showing that
      it is possible to synthetise small molecule analogues (SMAs) that mimic the anti
      inflammatory properties of ES-62, opening an exciting new drug development field
      in translational medicine. 

PMID- 24671113
TI  - Dynamics of soil bacterial communities in response to repeated application of
      manure containing sulfadiazine.
AB  - Large amounts of manure have been applied to arable soils as fertilizer
      worldwide. Manure is often contaminated with veterinary antibiotics which enter
      the soil together with antibiotic resistant bacteria. However, little information
      is available regarding the main responders of bacterial communities in soil
      affected by repeated inputs of antibiotics via manure. In this study, a microcosm
      experiment was performed with two concentrations of the antibiotic sulfadiazine
      (SDZ) which were applied together with manure at three different time points over
      a period of 133 days. Samples were taken 3 and 60 days after each manure
      application. The effects of SDZ on soil bacterial communities were explored by
      barcoded pyrosequencing of 16S rRNA gene fragments amplified from total community
      DNA. Samples with high concentration of SDZ were analyzed on day 193 only.
      Repeated inputs of SDZ, especially at a high concentration, caused pronounced
      changes in bacterial community compositions. By comparison with the initial soil,
      we could observe an increase of the disturbance and a decrease of the stability
      of soil bacterial communities as a result of SDZ manure application compared to
      the manure treatment without SDZ. The number of taxa significantly affected by
      the presence of SDZ increased with the times of manure application and was
      highest during the treatment with high SDZ-concentration. Numerous taxa, known to
      harbor also human pathogens, such as Devosia, Shinella, Stenotrophomonas,
      Clostridium, Peptostreptococcus, Leifsonia, Gemmatimonas, were enriched in the
      soil when SDZ was present while the abundance of bacteria which typically
      contribute to high soil quality belonging to the genera Pseudomonas and
      Lysobacter, Hydrogenophaga, and Adhaeribacter decreased in response to the
      repeated application of manure and SDZ. 

PMID- 24671114
TI  - Are Baby Boomers healthier than Generation X? A profile of Australia's working
      generations using National Health Survey data.
AB  - BACKGROUND: To determine differences in sociodemographic and health related
      characteristics of Australian Baby Boomers and Generation X at the same relative
      age. METHODS: The 1989/90 National Health Survey (NHS) for Boomers (1946-1965)
      and the 2007/08 NHS for Generation Xers (1966-1980) was used to compare the
      cohorts at the same age of 25-44 years. Generational differences for males and
      females in education, employment, smoking, physical activity, Body Mass Index
      (BMI), self-rated health, and diabetes were determined using Z tests. Prevalence
      estimates and p-values are reported. Logistic regression models examining
      overweight/obesity (BMI>=25) and diabetes prevalence as the dependent variables,
      with generation as the independent variable were adjusted for sex, age,
      education, physical activity, smoking and BMI(diabetes model only). Adjusted odds
      ratios (OR) and 95% confidence intervals are reported. RESULTS: At the same age,
      tertiary educational attainment was higher among Generation X males (27.6% vs.
      15.2% p<0.001) and females (30.0% vs. 10.6% p<0.001). Boomer females had a higher
      rate of unemployment (5.6% vs. 2.5% p<0.001). Boomer males and females had a
      higher prevalence of "excellent" self-reported health (35.9% vs. 21.8% p<0.001;
      36.3% vs. 25.1% p<0.001) and smoking (36.3% vs. 30.4% p<0.001; 28.3% vs. 22.3%
      p<0.001). Generation X males (18.3% vs. 9.4% p<0.001) and females (12.7% vs.
      10.4% p = 0.015) demonstrated a higher prevalence of obesity (BMI>30). There were
      no differences in physical activity. Modelling indicated that Generation X were
      more likely than Boomers to be overweight/obese (OR:2.09, 1.77-2.46) and have
      diabetes (OR:1.79, 1.47-2.18). CONCLUSION: Self-rated health has deteriorated
      while obesity and diabetes prevalence has increased. This may impact workforce
      participation and health care utilization in the future.

PMID- 24671115
TI  - A small-size transfer blackbody cavity for calibration of infrared ear
      thermometers.
AB  - A small-size transfer blackbody cavity for calibration of infrared ear
      thermometers (IRETs) was developed and characterized at the Korea Research
      Institute of Standards and Science. This blackbody cavity consists of a reflector
      exposed to the air and a radiator with three-step curves immersed in a water
      bath, and has an angularly uniform emissivity of higher than 0.9993. The radiance
      temperature of the blackbody cavity was measured with an IRET. We also calculated
      the effective emissivity by using the software STEEP322, considering the
      influence of the shape and temperature of the probe-tip of the IRET on the
      effective emissivity of the blackbody cavity. The measured and calculated
      radiance temperatures of the blackbody cavity were compared to those of the ASTM
      type blackbody cavity and are in good agreement. Uncertainties (k = 1) of the
      blackbody cavity are estimated to be less than 44 mK in the temperature range 35
      42  degrees C. 

PMID- 24671116
TI  - Pt nanoparticles supported on Sb-doped SnO2 porous structures: developments and
      issues.
AB  - In this work, high surface area antimony doped tin oxide (Sb-SnO2) has been
      synthesized using a modified sol-gel synthesis method. The bulk and surface
      properties of the metal oxide support have been investigated as a function of the
      processing conditions. A change in the Sb-SnO2 processing conditions, while
      preserving an overall invariant bulk composition, led to substantial modification
      of the surface stoichiometry. Accelerated stability test protocols have shown
      that the surface composition represents a crucial parameter for the
      electrochemical stability of Sb-SnO2. Model Pt/Sb-SnO2 electrodes have been
      developed depositing Pt nanoparticles by magnetron sputtering on the optimized Sb
      SnO2 porous surface. A significant enhancement in the corrosion stability upon
      1000 potential cycles between 0.5 and 1.5 V (RHE) at 50 mV s(-1) has been
      observed for the Pt/Sb-SnO2 system compared to Pt/carbon. 

PMID- 24671117
TI  - Density functional theory and Bader's atoms-in-molecules theory: towards a vivid
      dialogue.
AB  - Density functional theory and Bader's atoms-in-molecules theory share the same
      primary ingredient: the electron density, which is the fundamental physical
      observable in quantum chemistry. In this paper, we elaborate on the decomposition
      of the Kohn-Sham molecular energy in terms of Bader's partition, discussing how
      Pendas' Interacting Quantum Atoms framework could be adapted to a DFT context.
      Besides, another bridge between these two theories is built through a general
      formalism able to generate new local descriptors from any second-order density
      gradient expansion. These approaches are then applied to two classes of
      intramolecular bonds: between two electronegative atoms and intramolecular
      hydrogen bonds, illustrating how fruitful a dialog between both theories can be. 

PMID- 24671118
TI  - Enhancing the mechanical properties of BN nanosheet-polymer composites by
      uniaxial drawing.
AB  - We have used liquid exfoliation of hexagonal Boron-Nitride (BN) to prepare
      composites of BN nanosheets of three different sizes in polyvinylchloride
      matrices. These composites show low levels of reinforcement, consistent with poor
      alignment of the nanosheets as-described by a modified version of Halpin-Tsai
      theory. However, drawing of the composites to 300% strain results in a
      considerable increase in mechanical properties with the maximum composite modulus
      and strength both ~*3 higher than that of the pristine polymer. In addition, the
      rate of increase of modulus with BN volume fraction was up to 3-fold larger than
      for the unstrained composites. This is higher than can be explained by drawing
      induced alignment using Halpin-Tsai theory. However, the data was consistent with
      a combination of alignment and strain-induced de-aggregation of BN multilayers. 

PMID- 24671119
TI  - The associations between organizational culture, organizational structure and
      quality management in European hospitals.
AB  - OBJECTIVE: To better understand associations between organizational culture (OC),
      organizational management structure (OS) and quality management in hospitals.
      DESIGN: A multi-method, multi-level, cross-sectional observational study. SETTING
      AND PARTICIPANTS: As part of the DUQuE project (Deepening our Understanding of
      Quality improvement in Europe), a random sample of 188 hospitals in 7 countries
      (France, Poland, Turkey, Portugal, Spain, Germany and Czech Republic)
      participated in a comprehensive questionnaire survey and a one-day on-site
      surveyor audit. Respondents for this study (n = 158) included professional
      quality managers and hospital trustees. MAIN OUTCOME MEASURES: Extent of
      implementation of quality management systems, extent of compliance with existing
      management procedures and implementation of clinical quality activities. RESULTS:
      Among participating hospitals, 33% had a clan culture as their dominant culture
      type, 26% an open and developmental culture type, 16% a hierarchical culture type
      and 25% a rational culture type. The culture type had no statistically
      significant association with the outcome measures. Some structural
      characteristics were associated with the development of quality management
      systems. CONCLUSION: The type of OC was not associated with the development of
      quality management in hospitals. Other factors (not culture type) are associated
      with the development of quality management. An OS that uses fewer protocols is
      associated with a less developed quality management system, whereas an OS which
      supports innovation in care is associated with a more developed quality
      management system.

PMID- 24671120
TI  - Deepening our understanding of quality improvement in Europe (DUQuE): overview of
      a study of hospital quality management in seven countries.
AB  - INTRODUCTION AND OBJECTIVE: This paper provides an overview of the DUQuE
      (Deepening our Understanding of Quality Improvement in Europe) project, the first
      study across multiple countries of the European Union (EU) to assess
      relationships between quality management and patient outcomes at EU level. The
      paper describes the conceptual framework and methods applied, highlighting the
      novel features of this study. DESIGN: DUQuE was designed as a multi-level cross
      sectional study with data collection at hospital, pathway, professional and
      patient level in eight countries. SETTING AND PARTICIPANTS: We aimed to collect
      data for the assessment of hospital-wide constructs from up to 30 randomly
      selected hospitals in each country, and additional data at pathway and patient
      level in 12 of these 30. MAIN OUTCOME MEASURES: A comprehensive conceptual
      framework was developed to account for the multiple levels that influence
      hospital performance and patient outcomes. We assessed hospital-specific
      constructs (organizational culture and professional involvement), clinical
      pathway constructs (the organization of care processes for acute myocardial
      infarction, stroke, hip fracture and deliveries), patient-specific processes and
      outcomes (clinical effectiveness, patient safety and patient experience) and
      external constructs that could modify hospital quality (external assessment and
      perceived external pressure). RESULTS: Data was gathered from 188 hospitals in 7
      participating countries. The overall participation and response rate were between
      75% and 100% for the assessed measures. CONCLUSIONS: This is the first study
      assessing relation between quality management and patient outcomes at EU level.
      The study involved a large number of respondents and achieved high response
      rates. This work will serve to develop guidance in how to assess quality
      management and makes recommendations on the best ways to improve quality in
      healthcare for hospital stakeholders, payers, researchers, and policy makers
      throughout the EU.

PMID- 24671121
TI  - The use of on-site visits to assess compliance and implementation of quality
      management at hospital level.
AB  - OBJECTIVE: Stakeholders of hospitals often lack standardized tools to assess
      compliance with quality management strategies and the implementation of clinical
      quality activities in hospitals. Such assessment tools, if easy to use, could be
      helpful to hospitals, health-care purchasers and health-care inspectorates. The
      aim of our study was to determine the psychometric properties of two newly
      developed tools for measuring compliance with process-oriented quality management
      strategies and the extent of implementation of clinical quality strategies at the
      hospital level. DESIGN: We developed and tested two measurement instruments that
      could be used during on-site visits by trained external surveyors to calculate a
      Quality Management Compliance Index (QMCI) and a Clinical Quality Implementation
      Index (CQII). We used psychometric methods and the cross-sectional data to
      explore the factor structure, reliability and validity of each of these
      instruments. SETTING AND PARTICIPANTS: The sample consisted of 74 acute care
      hospitals selected at random from each of 7 European countries. MAIN OUTCOME
      MEASURES: The psychometric properties of the two indices (QMCI and CQII).
      RESULTS: Overall, the indices demonstrated favourable psychometric performance
      based on factor analysis, item correlations, internal consistency and hypothesis
      testing. Cronbach's alpha was acceptable for the scales of the QMCI (alpha: 0.74
      0.78) and the CQII (alpha: 0.82-0.93). Inter-scale correlations revealed that the
      scales were positively correlated, but distinct. All scales added sufficient new
      information to each main index to be retained. CONCLUSION: This study has
      produced two reliable instruments that can be used during on-site visits to
      assess compliance with quality management strategies and implementation of
      quality management activities by hospitals in Europe and perhaps other
      jurisdictions.

PMID- 24671122
TI  - Biological function and clinical relevance of chromogranin A and derived
      peptides.
AB  - Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co
      released with catecholamines and can function as a pro-hormone by giving rise to
      several bioactive peptides. This review summarizes the physiological functions,
      the pathogenic implications, and the recent use of these molecules as biomarkers
      in several pathological conditions. A thorough literature review of the
      electronic healthcare databases MEDLINE, from January 1985 to September 2013, was
      conducted to identify articles and studies concerned with CgA and its processing.
      The search strategies utilized keywords such as chromogranin A, vasostatins 1 and
      2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25,
      parastatin, and serpinin and was supplemented by the screening of references from
      included papers and review articles. A total of 209 English-language, peer
      reviewed original articles or reviews were examined. The analysis of the
      retrospective literature suggested that CgA and its several bioactive fragments
      exert a broad spectrum of regulatory activities by influencing the endocrine, the
      cardiovascular, and the immune systems and by affecting the glucose or calcium
      homeostasis. As some peptides exert similar effects, but others elicit opposite
      responses, the regulation of the CgA processing is critical to maintain
      homeostasis, whereas an unbalanced production of peptides that exert opposing
      effects can have a pathogenic role in several diseases. These clinical
      implications entail that CgA and its derived peptides are now used as diagnostic
      and prognostic markers or to monitor the response to pharmacological intervention
      not only in endocrine tumors, but also in cardiovascular, inflammatory, and
      neuropsychiatric diseases. 

PMID- 24671123
TI  - Functional studies of novel CYP21A2 mutations detected in Norwegian patients with
      congenital adrenal hyperplasia.
AB  - In about 95% of cases, congenital adrenal hyperplasia (CAH) is caused by
      mutations in CYP21A2 gene encoding steroid 21-hydroxylase (21OH). Recently, we
      have reported four novel CYP21A2 variants in the Norwegian population of patients
      with CAH, of which p.L388R and p.E140K were associated with salt wasting (SW),
      p.P45L with simple virilising (SV) and p.V211M+p.V281L with SV to non-classical
      (NC) phenotypes. We aimed to characterise the novel variants functionally
      utilising a newly designed in vitro assay of 21OH enzyme activity and structural
      simulations and compare the results with clinical phenotypes. CYP21A2 mutations
      and variants were expressed in vitro. Enzyme activity was assayed by assessing
      the conversion of 17-hydroxyprogesterone to 11-deoxycortisol by liquid
      chromatography tandem mass spectroscopy. PyMOL 1.3 was used for structural
      simulations, and PolyPhen2 and PROVEAN for predicting the severity of the
      mutants. The CYP21A2 mutants, p.L388R and p.E140K, exhibited 1.1 and 11.3% of wt
      21OH enzyme activity, respectively, in vitro. We could not detect any functional
      deficiency of the p.P45L variant in vitro; although prediction tools suggest
      p.P45L to be pathogenic. p.V211M displayed enzyme activity equivalent to the wt
      in vitro, which was supported by in silico analyses. We found good correlations
      between phenotype and the in vitro enzyme activities of the SW mutants, but not
      for the SV p.P45L variant. p.V211M might have a synergistic effect together with
      p.V281L, explaining a phenotype between SV and NC CAH. 

PMID- 24671124
TI  - Efficacy of increased resistant starch consumption in human type 2 diabetes.
AB  - Resistant starch (RS) has been shown to beneficially affect insulin sensitivity
      in healthy individuals and those with metabolic syndrome, but its effects on
      human type 2 diabetes (T2DM) are unknown. This study aimed to determine the
      effects of increased RS consumption on insulin sensitivity and glucose control
      and changes in postprandial metabolites and body fat in T2DM. Seventeen
      individuals with well-controlled T2DM (HbA1c 46.6+/-2 mmol/mol) consumed, in a
      random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks
      with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD,
      PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic
      hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal
      tolerance test (MTT) with arterio-venous sampling across the forearm, and whole
      body imaging. HAM-RS2 resulted in significantly lower postprandial glucose
      concentrations (P=0.045) and a trend for greater glucose uptake across the
      forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or
      peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid
      (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was
      greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG)
      concentrations and soleus intramuscular TG concentrations were significantly
      higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively).
      Although fasting GLP1 concentrations were significantly lower following HAM-RS2
      consumption (P=0.049), postprandial GLP1 excursions during the MTT were
      significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin
      sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal
      handling, possibly due to higher postprandial GLP1. 

PMID- 24671125
TI  - Mast cells, basophils and B cell connection network.
AB  - It has been proven that both resting and activated mast cells (MCs) and basophils
      are able to induce a significant increase in proliferation and survival of naive
      and activated B cells, and their differentiation into antibody-producing cells.
      The immunological context in which this regulation occurs is of particular
      interest and the idea that these innate cells induce antibody class switching and
      production is increasingly gaining ground. This direct role of MCs and basophils
      in acquired immunity requires cell to cell contact as well as soluble factors and
      exosomes. Here, we review our current understanding of the interaction between B
      cells and MCs or basophils as well as the evidence supporting B lymphocyte
      MC/basophil crosstalk in pathological settings. Furthermore, we underline the
      obscure aspects of this interaction that could serve as important starting points
      for future research in the field of MC and basophil biology in the peculiar
      context of the connection between innate and adaptive immunity. 

PMID- 24671127
TI  - Widespread use and frequent detection of neonicotinoid insecticides in wetlands
      of Canada's Prairie Pothole Region.
AB  - Neonicotinoids currently dominate the insecticide market as seed treatments on
      Canada's major Prairie crops (e.g., canola). The potential impact to ecologically
      significant wetlands in this dominantly agro-environment has largely been
      overlooked while the distribution of use, incidence and level of contamination
      remains unreported. We modelled the spatial distribution of neonicotinoid use
      across the three Prairie Provinces in combination with temporal assessments of
      water and sediment concentrations in wetlands to measure four active ingredients
      (clothianidin, thiamethoxam, imidacloprid and acetamiprid). From 2009 to 2012,
      neonicotinoid use was increasing; by 2012, applications covered an estimated ~11
      million hectares (44% of Prairie cropland) with >216,000 kg of active
      ingredients. Thiamethoxam, followed by clothianidin, were the dominant seed
      treatments by mass and area. Areas of high neonicotinoid use were identified as
      high density canola or soybean production. Water sampled four times from 136
      wetlands (spring, summer, fall 2012 and spring 2013) across four rural
      municipalities in Saskatchewan similarly revealed clothianidin and thiamethoxam
      in the majority of samples. In spring 2012 prior to seeding, 36% of wetlands
      contained at least one neonicotinoid. Detections increased to 62% in summer 2012,
      declined to 16% in fall, and increased to 91% the following spring 2013 after ice
      off. Peak concentrations were recorded during summer 2012 for both thiamethoxam
      (range: <LOQ--1490 ng/L, canola) and clothianidin (range: <LOQ--3110 ng/L,
      canola). Sediment samples collected during the same period rarely (6%) contained
      neonicotinoid concentrations (which did not exceed 20 ng/L). Wetlands situated in
      barley, canola and oat fields consistently contained higher mean concentrations
      of neonicotinoids than in grasslands, but no individual crop singularly
      influenced overall detections or concentrations. Distribution maps indicate
      neonicotinoid use is increasing and becoming more widespread with concerns for
      environmental loading, while frequently detected neonicotinoid concentrations in
      Prairie wetlands suggest high persistence and transport into wetlands.

PMID- 24671128
TI  - Introduction to super-resolution microscopy.
AB  - In this review, we introduce the principles of spatial resolution improvement in
      super-resolution microscopies that were recently developed. These super
      resolution techniques utilize the interaction of light and fluorescent probes in
      order to break the diffraction barrier that limits spatial resolution. The
      imaging property of each super-resolution technique is also compared with the
      corresponding conventional one. Typical applications of the super-resolution
      techniques in biological research are also introduced. 

PMID- 24671129
TI  - Suboptimal herd performance amplifies the spread of infectious disease in the
      cattle industry.
AB  - Farms that purchase replacement breeding cattle are at increased risk of
      introducing many economically important diseases. The objectives of this analysis
      were to determine whether the total number of replacement breeding cattle
      purchased by individual farms could be reduced by improving herd performance and
      to quantify the effects of such reductions on the industry-level transmission
      dynamics of infectious cattle diseases. Detailed information on the performance
      and contact patterns of British cattle herds was extracted from the national
      cattle movement database as a case example. Approximately 69% of beef herds and
      59% of dairy herds with an average of at least 20 recorded calvings per year
      purchased at least one replacement breeding animal. Results from zero-inflated
      negative binomial regression models revealed that herds with high average ages at
      first calving, prolonged calving intervals, abnormally high or low culling rates,
      and high calf mortality rates were generally more likely to be open herds and to
      purchase greater numbers of replacement breeding cattle. If all herds achieved
      the same level of performance as the top 20% of herds, the total number of
      replacement beef and dairy cattle purchased could be reduced by an estimated 34%
      and 51%, respectively. Although these purchases accounted for only 13% of between
      herd contacts in the industry trade network, they were found to have a
      disproportionately strong influence on disease transmission dynamics. These
      findings suggest that targeting extension services at herds with suboptimal
      performance may be an effective strategy for controlling endemic cattle diseases
      while simultaneously improving industry productivity. 

PMID- 24671130
TI  - Structural and functional cerebral correlates of hypnotic suggestibility.
AB  - Little is known about the neural bases of hypnotic suggestibility, a cognitive
      trait referring to the tendency to respond to hypnotic suggestions. In the
      present magnetic resonance imaging study, we performed regression analyses to
      assess hypnotic suggestibility-related differences in local gray matter volume,
      using voxel-based morphometry, and in waking resting state functional
      connectivity of 10 resting state networks, in 37 healthy women. Hypnotic
      suggestibility was positively correlated with gray matter volume in portions of
      the left superior and medial frontal gyri, roughly overlapping with the
      supplementary and pre-supplementary motor area, and negatively correlated with
      gray matter volume in the left superior temporal gyrus and insula. In the
      functional connectivity analysis, hypnotic suggestibility was positively
      correlated with functional connectivity between medial posterior areas, including
      bilateral posterior cingulate cortex and precuneus, and both the lateral visual
      network and the left fronto-parietal network; a positive correlation was also
      found with functional connectivity between the executive-control network and a
      right postcentral/parietal area. In contrast, hypnotic suggestibility was
      negatively correlated with functional connectivity between the right fronto
      parietal network and the right lateral thalamus. These findings demonstrate for
      the first time a correlation between hypnotic suggestibility, the structural
      features of specific cortical regions, and the functional connectivity during the
      normal resting state of brain structures involved in imagery and self-monitoring
      activity. 

PMID- 24671131
TI  - Cardiovascular risk and psoriasis: a role in clinical cardiology?

PMID- 24671132
TI  - Neutrophil-lymphocyte ratio and carotid-intima media thickness in patients with
      Behcet disease without cardiovascular involvement.
AB  - Behcet disease (BD) is associated with endothelial dysfunction and chronic
      inflammation. The neutrophil-lymphocyte (N/L) ratio and carotid intima-media
      thickness (cIMT) are markers of inflammation and vascular risk, respectively. We
      assessed the relationship between cIMT values and N/L ratio in BD (65 patients
      and 62 control participants). There were statistically significant differences in
      N/L ratios and cIMT values between the patients with BD and control group (P <
      .001). There were moderate positive correlations between cIMT value, C-reactive
      protein, and N/L ratio in patients with BD. Receiver-operating characteristic
      curve analysis suggested that the optimum N/L ratio cutoff point for patients
      with BD was 1.29, with a sensitivity, specificity, negative predictive value, and
      positive predictive value of 97, 77, 96, and 75%, respectively (area under curve:
      0.691, 95% confidence interval = 0.600-0.782, P < .001). The N/L ratio may be a
      useful index of BD activity. 

PMID- 24671133
TI  - Mate preference of female blue tits varies with experimental photoperiod.
AB  - Organisms use environmental cues to time their life-cycles and among these cues,
      photoperiod is the main trigger of reproductive behaviours such as territory
      defence or song activity. Whether photoperiod is also important for another
      behaviour closely associated with reproduction, mate choice, is unknown. In many
      bird species, mate choice occurs at two different times during the annual cycle
      that strongly differ in daylength: in late winter when photoperiod is short and
      social mates are chosen, and again around egg-laying when photoperiod is longer
      and extra-pair mates are chosen. This duality makes the role that photoperiod
      plays on mate choice behaviours intriguing. We investigated the effect of
      photoperiod on mate choice using three experimental photoperiodic treatments (9
      L:15 D, 14 L:10 D, 18 L:6 D), using blue tits (Cyanistes caeruleus) as a
      biological model. We show that female choice was stronger under long
      photoperiods. In addition, female blue tits spent significantly more time near
      males with long tarsi and long wings. This latter preference was only expressed
      under long photoperiods, suggesting that some indices of male quality only become
      significant to females when they are strongly photostimulated, and therefore that
      females could select their social and extra-pair mates based on different
      phenotypic traits. These results shed light on the roles that photoperiod may
      play in stimulating pair-bonding and in refining female selectivity for male
      traits. 

PMID- 24671134
TI  - Reconstruction of ancestral brains: exploring the evolutionary process of
      encephalization in amniotes.
AB  - There is huge divergence in the size and complexity of vertebrate brains.
      Notably, mammals and birds have bigger brains than other vertebrates, largely
      because these animal groups established larger dorsal telencephali. Fossil
      evidence suggests that this anatomical trait could have evolved independently.
      However, recent comparative developmental analyses demonstrate surprising
      commonalities in neuronal subtypes among species, although this interpretation is
      highly controversial. In this review, we introduce intriguing evidence regarding
      brain evolution collected from recent studies in paleontology and developmental
      biology, and we discuss possible evolutionary changes in the cortical
      developmental programs that led to the encephalization and structural complexity
      of amniote brains. New research concepts and approaches will shed light on the
      origin and evolutionary processes of amniote brains, particularly the mammalian
      cerebral cortex. 

PMID- 24671135
TI  - Comparative sensitivity of commonly used thromboplastins to ex vivo therapeutic
      rivaroxaban levels.

PMID- 24671136
TI  - A cognitive ethology study of first- and third-person perspectives.
AB  - The aim of the present study was to test the cognitive ethology approach, which
      seeks to link cognitions and behaviours as they operate in everyday life with
      those studied in controlled lab-based investigations. Our test bed was the
      understanding of first-person and third-person perspectives, which in lab-based
      investigations have been defined in a diverse and multi-faceted manner. We
      hypothesized that because these lab-based investigations seek to connect with how
      first- and third-person perspective operates in everyday life, then either some
      of the divergent lab-based definitions are missing their mark or the everyday
      conceptualization of first- and third-person perspective is multi-faceted. Our
      investigation revealed the latter. By applying a cognitive ethology approach we
      were able to determine that a) peoples' everyday understanding of perspective is
      diverse yet reliable, and b) a lab-based investigation that applies these diverse
      understandings in a controlled setting can accurately predict how people will
      perform. These findings provide a 'proof of concept' for the cognitive ethology
      approach. Moreover, the present data demonstrate that previous lab-based studies,
      that often had very different understandings of first- and third-person
      perspective, were each in and of themselves valid. That is, each is capturing
      part of a broader understanding of perspective in everyday life. Our results also
      revealed a novel social factor not included in traditional conceptualizations of
      first-person third-perspective, that of eye gaze, i.e., eye contact is equated
      strongly with first-person perspective and the lack of eye-contact with third
      person perspective. 

PMID- 24671137
TI  - Phagocytosis via complement or Fc-gamma receptors is compromised in monocytes
      from type 2 diabetes patients with chronic hyperglycemia.
AB  - Type 2 diabetes patients (DM2) have a higher risk of tuberculosis (TB) that may
      be attributed to functional defects in their mononuclear phagocytes given the
      critical role of these cells in Mycobacterium tuberculosis containment. Our
      previous findings suggest that monocytes from DM2 have reduced association with
      serum-opsonized M. tuberculosis. To determine if this alteration is due to
      defects in phagocytosis via complement or Fc-gamma receptors (FcgammaRs), in this
      study we evaluated the uptake of sheep red blood cells coated with IgG or
      complement, respectively, by monocytes from individuals with and without DM2. We
      found that chronic hyperglycemia was significantly associated with reduced
      phagocytosis via either receptor by univariable and multivariable analyses. This
      defect was independent of host serum opsonins and flow cytometry data indicated
      this was not attributed to reduced expression of these phagocytic receptors on
      DM2 monocytes. The positive correlation between both pathways (R = 0.64; p =
      0.003) indicate that monocytes from individuals with chronic hyperglycemia have a
      defect in the two predominant phagocytic pathways of these cells. Given that
      phagocytosis is linked to activation of effector mechanisms for bacterial
      killing, it is likely that this defect is one factor contributing to the higher
      susceptibility of DM2 patients to pathogens like M. tuberculosis. 

PMID- 24671138
TI  - The origin of novel avian influenza A (H7N9) and mutation dynamics for its human
      to-human transmissible capacity.
AB  - In February 2013, H7N9 (A/H7N9/2013_China), a novel avian influenza virus, broke
      out in eastern China and caused human death. It is a global priority to discover
      its origin and the point in time at which it will become transmittable between
      humans. We present here an interdisciplinary method to track the origin of H7N9
      virus in China and to establish an evolutionary dynamics model for its human-to
      human transmission via mutations. After comparing influenza viruses from China
      since 1983, we established an A/H7N9/2013_China virus evolutionary phylogenetic
      tree and found that the human instances of virus infection were of avian origin
      and clustered into an independent line. Comparing hemagglutinin (HA) and
      neuraminidase (NA) gene sequences of A/H7N9/2013_China viruses with all human-to
      human, avian, and swine influenza viruses in China in the past 30 years, we found
      that A/H7N9/2013_China viruses originated from Baer's Pochard H7N1 virus of Hu
      Nan Province 2010 (HA gene, EPI: 370846, similarity with H7N9 is 95.5%) and duck
      influenza viruses of Nanchang city 2000 (NA gene, EPI: 387555, similarity with
      H7N9 is 97%) through genetic re-assortment. HA and NA gene sequence comparison
      indicated that A/H7N9/2013_China virus was not similar to human-to-human
      transmittable influenza viruses. To simulate the evolution dynamics required for
      human-to-human transmission mutations of H7N9 virus, we employed the Markov
      model. The result of this calculation indicated that the virus would acquire
      properties for human-to-human transmission in 11.3 years (95% confidence interval
      (CI): 11.2-11.3, HA gene). 

PMID- 24671140
TI  - Quantitative description of the 3D regional mechanics of the left atrium using
      cardiac magnetic resonance imaging.
AB  - The left atrium (LA) plays an important role in the maintenance of hemodynamic
      and electrical stability of the heart. One of the conditions altering the atrial
      mechanical function is atrial fibrillation (AF), leading to an increased
      thromboembolic risk due to impaired mechanical function. Preserving the regions
      of the LA that contribute the greatest to atrial mechanical function during
      curative strategies for AF is important. The purpose of this study is to
      introduce a novel method of regional assessment of mechanical function of the LA.
      We used cardiac MRI to reconstruct the 3D geometry of the LA in nine control and
      nine patients with paroxysmal atrial fibrillation (PAF). Regional mechanical
      function of the LA in pre-defined segments of the atrium was calculated using
      regional ejection fraction and wall velocity. We found significantly greater
      mechanical function in anterior, septal and lateral segments as opposed to roof
      and posterior segments, as well as a significant decrease of mechanical function
      in the PAF group. We suggest that in order to minimize the impact of the AF
      treatment on global atrial mechanical function, damage related to therapeutic
      intervention, such as catheter ablation, in those areas should be minimized. 

PMID- 24671139
TI  - Glycan masking of hemagglutinin for adenovirus vector and recombinant protein
      immunizations elicits broadly neutralizing antibodies against H5N1 avian
      influenza viruses.
AB  - The highly pathogenic avian influenza (HPAI) H5N1 virus, a known trigger of
      diseases in poultry and humans, is perceived as a serious threat to public
      health. There is a clear need for a broadly protective H5N1 vaccine or vaccines
      for inducing neutralizing antibodies against multiple clades/subclades. We
      constructed single, double, and triple mutants of glycan-masked hemagglutiinin
      (HA) antigens at residues 83, 127 and 138 (i.e., g83, g127, g138, g83+g127,
      g127+g138, g83+g138 and g83+g127+g138), and then obtained their corresponding HA
      expressing adenovirus vectors and recombinant HA proteins using a prime-boost
      immunization strategy. Our results indicate that the glycan-masked g127+g138
      double mutant induced more potent HA-inhibition, virus neutralization antibodies,
      cross-clade protection against heterologous H5N1 clades, correlated with the
      enhanced bindings to the receptor binding sites and the highly conserved stem
      region of HA. The immune refocusing stem-specific antibodies elicited by the
      glycan-masked H5HA g127+g138 and g83+g127+g138 mutants overlapped with broadly
      neutralizing epitopes of the CR6261 monoclonal antibody that neutralizes most
      group 1 subtypes. These findings may provide useful information in the
      development of a broadly protective H5N1 influenza vaccine. 

PMID- 24671142
TI  - Molecular resonant dissociation of surface-adsorbed molecules by plasmonic
      nanoscissors.
AB  - The ability to break individual bonds or specific modes in chemical reactions is
      an ardently sought goal by chemists and physicists. While photochemistry based
      methodologies are very successful in controlling e.g. photocatalysis,
      photosynthesis and the degradation of plastic, it is hard to break individual
      molecular bonds for those molecules adsorbed on the surface because of the weak
      light-absorption in molecules and the redistribution of the resulting vibrational
      energy both inside the molecule and to its surrounding environment. Here we show
      how to overcome these obstacles with a plasmonic hot-electron mediated process
      and demonstrate a new method that allows the sensitive control of resonant
      dissociation of surface-adsorbed molecules by 'plasmonic' scissors. To that end,
      we used a high-vacuum tip-enhanced Raman spectroscopy (HV-TERS) setup to
      dissociate resonantly excited NC2H6 fragments from Malachite green. The surface
      plasmons (SPs) excited at the sharp metal tip not only enhance the local electric
      field to harvest the light incident from the laser, but crucially supply 'hot
      electrons' whose energy can be transferred to individual bonds. These processes
      are resonant Raman, which result in some active chemical bonds and then weaken
      these bonds, followed by dumping in lots of indiscriminant energy and breaking
      the weakest bond. The method allows for sensitive control of both the rate and
      probability of dissociation through their dependence on the density of hot
      electrons, which can be manipulated by tuning the laser intensity or tunneling
      current/bias voltage in the HV-TERS setup, respectively. The concepts of
      plasmonic scissors open up new versatile avenues for the deep understanding of in
      situ surface-catalyzed chemistry. 

PMID- 24671146
TI  - Hierarchical mesoporous iron-based fluoride with partially hollow structure:
      facile preparation and high performance as cathode material for rechargeable
      lithium ion batteries.
AB  - Hierarchical mesoporous structured iron based fluorides (abbreviated as HMIFs)
      are successfully synthesized for the first time by a solvothermal method through
      self-assembly. The fluorides are built from a large amount of nanorods with a
      size more than a dozen nanometers and exhibit dual phases consisting of
      Fe1.9F4.75.0.95H2O and FeF3.H2O. A possible formation mechanism is proposed by
      systematically investigating the synthesis conditions including temperature,
      reaction time and the amount of the fluorides source. The electrochemical
      performance of HMIFs as cathodes for rechargeable lithium batteries is
      investigated. A large reversible capacity exceeding 200 mA h g(-1) without any
      conducting agent coating and excellent cyclic performance with a residual
      capacity of 148 mA h g(-1) after 100 cycles are obtained at 0.1 C. In addition,
      an outstanding rate performance exceeding 100 mA h g(-1) at 5 C highlights the
      advantages of HMIFs materials for energy storage applications in high-performance
      LIBs. 

PMID- 24671141
TI  - Mediation of the relationship between callous-unemotional traits and proactive
      aggression by amygdala response to fear among children with conduct problems.
AB  - IMPORTANCE: Among youths with conduct problems, callous-unemotional (CU) traits
      are known to be an important determinant of symptom severity, prognosis, and
      treatment responsiveness. But positive correlations between conduct problems and
      CU traits result in suppressor effects that may mask important neurobiological
      distinctions among subgroups of children with conduct problems. OBJECTIVE: To
      assess the unique neurobiological covariates of CU traits and externalizing
      behaviors in youths with conduct problems and determine whether neural
      dysfunction linked to CU traits mediates the link between callousness and
      proactive aggression. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional
      case-control study involved behavioral testing and neuroimaging that were
      conducted at a university research institution. Neuroimaging was conducted using
      a 3-T Siemens magnetic resonance imaging scanner. It included 46 community
      recruited male and female juveniles aged 10 to 17 years, including 16 healthy
      control participants and 30 youths with conduct problems with both low and high
      levels of CU traits. MAIN OUTCOMES AND MEASURES: Blood oxygenation level
      dependent signal as measured via functional magnetic resonance imaging during an
      implicit face-emotion processing task and analyzed using whole-brain and region
      of interest-based analysis of variance and multiple-regression analyses. RESULTS:
      Analysis of variance revealed no group differences in the amygdala. By contrast,
      consistent with the existence of suppressor effects, multiple-regression analysis
      found amygdala responses to fearful expressions to be negatively associated with
      CU traits (x = 26, y = 0, z = -12; k = 1) and positively associated with
      externalizing behavior (x = 24, y = 0, z = -14; k = 8) when both variables were
      modeled simultaneously. Reduced amygdala responses mediated the relationship
      between CU traits and proactive aggression. CONCLUSIONS AND RELEVANCE: The
      results linked proactive aggression in youths with CU traits to hypoactive
      amygdala responses to emotional distress cues, consistent with theories that
      externalizing behaviors, particularly proactive aggression, in youths with these
      traits stem from deficient empathic responses to distress. Amygdala hypoactivity
      may represent an intermediate phenotype, offering new insights into effective
      treatment strategies for conduct problems.

PMID- 24671147
TI  - Design factors that influence the performance of flight intercept traps for the
      capture of longhorned beetles (Coleoptera: Cerambycidae) from the subfamilies
      Lamiinae and Cerambycinae.
AB  - In North America, cerambycid beetles can have significant ecological and economic
      effects on forest ecosystems, and the rate of introduction and/or detection of
      exotic species is increasing. Detection and survey programs rely on semiochemical
      baited intercept traps which are often ineffective for large woodborers like
      cerambycid beetles. This study examined the effects of flight intercept trap
      design on the capture of cerambycid beetles in the subfamilies Lamiinae and
      Cerambycinae. These subfamilies are the two largest in the Cerambycidae and they
      include many of the most damaging cerambycid pests and species on regulatory
      watch lists in North America. This study demonstrates that intercept trap design,
      treatment of trap surfaces with a lubricant, and the type of collection cup all
      influence the capture of beetles from the subfamilies Lamiinae and Cerambycinae.
      It also demonstrates that the addition of a large lubricant-treated collar to the
      bottom funnel of a multiple-funnel trap significantly increases the capture of
      some Lamiinae. The best trap design for both subfamilies was a lubricant treated
      multiple-funnel [MF] trap equipped with a wet cup and lubricant treated large
      collar on the bottom funnel. This design captured between 4 and 14 times more
      Lamiinae and Cerambycinae than commercially-available MF and panel traps. 

PMID- 24671148
TI  - Zeolites as catalysts in oil refining.
AB  - Oil is nowadays the main energy source and this prevalent position most probably
      will continue in the next decades. This situation is largely due to the degree of
      maturity that has been achieved in oil refining and petrochemistry as a
      consequence of the large effort in research and innovation. The remarkable
      efficiency of oil refining is largely based on the use of zeolites as catalysts.
      The use of zeolites as catalysts in refining and petrochemistry has been
      considered as one of the major accomplishments in the chemistry of the XXth
      century. In this tutorial review, the introductory part describes the main
      features of zeolites in connection with their use as solid acids. The main body
      of the review describes important refining processes in which zeolites are used
      including light naphtha isomerization, olefin alkylation, reforming, cracking and
      hydrocracking. The final section contains our view on future developments in the
      field such as the increase in the quality of the transportation fuels and the
      coprocessing of increasing percentage of biofuels together with oil streams. This
      review is intended to provide the rudiments of zeolite science applied to
      refining catalysis. 

PMID- 24671149
TI  - Let's eat, let's worry.

PMID- 24671150
TI  - Cationic peptide exposure enhances pulsed-electric-field-mediated membrane
      disruption.
AB  - BACKGROUND: The use of pulsed electric fields (PEFs) to irreversibly
      electroporate cells is a promising approach for destroying undesirable cells.
      This approach may gain enhanced applicability if the intensity of the PEF
      required to electrically disrupt cell membranes can be reduced via exposure to a
      molecular deliverable. This will be particularly impactful if that reduced PEF
      minimally influences cells that are not exposed to the deliverable. We
      hypothesized that the introduction of charged molecules to the cell surfaces
      would create regions of enhanced transmembrane electric potential in the vicinity
      of each charged molecule, thereby lowering the PEF intensity required to disrupt
      the plasma membranes. This study will therefore examine if exposure to cationic
      peptides can enhance a PEF's ability to disrupt plasma membranes.
      METHODOLOGY/PRINCIPAL FINDINGS: We exposed leukemia cells to 40 MUs PEFs in media
      containing varying concentrations of a cationic peptide, polyarginine. We
      observed the internalization of a membrane integrity indicator, propidium iodide
      (PI), in real time. Based on an individual cell's PI fluorescence versus time
      signature, we were able to determine the relative degree of membrane disruption.
      When using 1-2 kV/cm, exposure to >50 MUg/ml of polyarginine resulted in
      immediate and high levels of PI uptake, indicating severe membrane disruption,
      whereas in the absence of peptide, cells predominantly exhibited signatures
      indicative of no membrane disruption. Additionally, PI entered cells through the
      anode-facing membrane when exposed to cationic peptide, which was theoretically
      expected. CONCLUSIONS/SIGNIFICANCE: Exposure to cationic peptides reduced the PEF
      intensity required to induce rapid and irreversible membrane disruption.
      Critically, peptide exposure reduced the PEF intensities required to elicit
      irreversible membrane disruption at normally sub-electroporation intensities. We
      believe that these cationic peptides, when coupled with current advancements in
      cell targeting techniques will be useful tools in applications where targeted
      destruction of unwanted cell populations is desired.

PMID- 24671152
TI  - Comprehensive behavioural analysis of Long Evans and Sprague-Dawley rats reveals
      differential effects of housing conditions on tests relevant to neuropsychiatric
      disorders.
AB  - Genetic (G) and environmental (E) manipulations are known to alter behavioural
      outcomes in rodents, however many animal models of neuropsychiatric disorders
      only use a restricted selection of strain and housing conditions. The aim of this
      study was to examine GxE interactions comparing two outbred rat strains, which
      were housed in either standard or enriched cages. The strains selected were the
      albino Sprague-Dawley rat, commonly used for animal models, and the other was the
      pigmented Long Evans rat, which is frequently used in cognitive studies. Rats
      were assessed using a comprehensive behavioural test battery and included well
      established tests frequently employed to examine animal models of
      neuropsychiatric diseases, measuring aspects of anxiety, exploration,
      sensorimotor gating and cognition. Selective strain and housing effects were
      observed on a number of tests. These included increased locomotion and reduced
      pre-pulse inhibition in Long Evans rats compared to Sprague Dawley rats; and rats
      housed in enriched cages had reduced anxiety-like behaviour compared to standard
      housed rats. Long Evans rats required fewer sessions than Sprague Dawley rats to
      learn operant tasks, including a signal detection task and reversal learning.
      Furthermore, Long Evans rats housed in enriched cages acquired simple operant
      tasks faster than standard housed Long Evans rats. Cognitive phenotypes in animal
      models of neuropsychiatric disorders would benefit from using strain and housing
      conditions where there is greater potential for both enhancement and deficits in
      performance. 

PMID- 24671153
TI  - Functional characterization of two low-density lipoprotein receptor gene
      mutations in two Chinese patients with familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease
      that primarily results from mutations in the low-density lipoprotein receptor
      (LDLR) gene. We investigated two unrelated Chinese FH patients using gene
      screening and functional analysis to reveal the pathogenicity and the mechanism
      by which these mutations cause FH. METHODS: First, the LDLR gene was sequenced in
      these patients. Then, mutant receptors were transfected into human embryo kidney
      293 (HEK-293) cells, and a confocal laser-scanning microscope was used to observe
      the localization of mutant proteins. Further, the expression and the
      internalization activity were analyzed by flow cytometry. Finally, LDLR protein
      expression and stability was detected by western blot. RESULTS: Two different
      LDLR class 2B mutations were detected in two patients. The C201F mutation is a
      known mutation. However, the G615V mutation is novel. Flow cytometry showed that
      the expression and internalization activity of the mutant LDLRs were reduced to
      73.6% and 82.6% for G615V and 33.2% and 33.5% for C201F, respectively.
      CONCLUSIONS: This study identified two LDLR mutations in Chinese patients with FH
      and analyzed the relationship between the genotype and phenotype of these
      patients. We found that these mutant LDLRs were defective in transport, which led
      to a reduction in cholesterol clearance. These results increase our understanding
      of the mutational spectrum of FH in the Chinese population.

PMID- 24671154
TI  - A novel oncolytic herpes simplex virus type 2 has potent anti-tumor activity.
AB  - Oncolytic viruses are promising treatments for many kinds of solid tumors. In
      this study, we constructed a novel oncolytic herpes simplex virus type 2: oHSV2.
      We investigated the cytopathic effects of oHSV2 in vitro and tested its antitumor
      efficacy in a 4T1 breast cancer model. We compared its effect on the cell cycle
      and its immunologic impact with the traditional chemotherapeutic agent
      doxorubicin. In vitro data showed that oHSV2 infected most of the human and
      murine tumor cell lines and was highly oncolytic. oHSV2 infected and killed 4T1
      tumor cells independent of their cell cycle phase, whereas doxorubicin mainly
      blocked cells that were in S and G2/M phase. In vivo study showed that both oHSV2
      and doxorubicin had an antitumor effect, though the former was less toxic. oHSV2
      treatment alone not only slowed down the growth of tumors without causing weight
      loss but also induced an elevation of NK cells and mild decrease of Tregs in
      spleen. In addition, combination therapy of doxorubicin followed by oHSV2
      increased survival with weight loss than oHSV2 alone. The data showed that the
      oncolytic activity of oHSV2 was similar to oHSV1 in cell lines examined and in
      vivo. Therefore, we concluded that our virus is a safe and effective therapeutic
      agent for 4T1 breast cancer and that the sequential use of doxorubicin followed
      by oHSV2 could improve antitumor activity without enhancing doxorubicin's
      toxicity. 

PMID- 24671156
TI  - Patterns of deep-water coral diversity in the Caribbean Basin and adjacent
      southern waters: an approach based on records from the R/V Pillsbury expeditions.
AB  - The diversity of deep-water corals in the Caribbean Sea was studied using records
      from oceanographic expeditions performed by the R/V Pillsbury. Sampled stations
      were sorted according to broad depth ranges and ecoregions and were analyzed in
      terms of species accumulation curves, variance in the species composition and
      contributions to alpha, beta and gamma diversity. According to the analysis of
      species accumulation curves using the Chao2 estimator, more diversity occurs on
      the continental slope (200-2000 m depth) than on the upper continental shelf (60
      200 m depth). In addition to the effect of depth sampling, differences in species
      composition related to depth ranges were detected. However, the differences
      between ecoregions are dependent on depth ranges, there were fewer differences
      among ecoregions on the continental slope than on the upper continental shelf.
      Indicator species for distinctness of ecoregions were, in general, Alcyonaria and
      Antipatharia for the upper continental shelf, but also the scleractinians
      Madracis myriabilis and Cladocora debilis. In the continental slope, the
      alcyonarian Placogorgia and the scleractinians Stephanocyathus and Fungiacyathus
      were important for the distinction of ecoregions. Beta diversity was the most
      important component of gamma diversity in the Caribbean Basin. The contribution
      of ecoregions to alpha, beta and gamma diversity differed with depth range. On
      the upper continental shelf, the Southern Caribbean ecoregion contributed
      substantially to all components of diversity. In contrast, the northern
      ecoregions contributed substantially to the diversity of the Continental Slope.
      Strategies for the conservation of deep-water coral diversity in the Caribbean
      Basin must consider the variation between ecoregions and depth ranges. 

PMID- 24671155
TI  - Dynamic cerebral autoregulation is heterogeneous in different subtypes of acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Stroke of large-artery atherosclerosis and small-artery
      occlusion are two main subtypes of stroke according to TOAST classification. The
      underlying mechanisms of how these two subtypes affect dynamic cerebral
      autoregulation (dCA) might be heterogeneous, resulting in varied clinical
      conditions and outcomes. We therefore studied the pattern of dCA in these two
      subtypes. METHODS: Forty-one patients with acute unilateral middle cerebral
      artery (MCA) territory stroke (15 with ipsilateral large-artery atherosclerosis
      and 26 with small-artery occlusion) and 20 healthy volunteers were enrolled. Non
      invasive continuous cerebral blood flow velocity and arterial blood pressure were
      recorded simultaneously from each subject in supine position using transcranial
      Doppler on MCA bilaterally and servo-controlled plethysmograph on the middle
      finger, respectively. Transfer function analysis was applied to derive
      autoregulatory parameters, gain, phase difference (PD), and slope of step
      response. RESULTS: In the large-artery atherosclerosis group, PD in affected
      hemisphere was 42.9+/-18.5 degree, which is significantly lower than the
      unaffected hemisphere (72.4+/-29.9 degree, P<0.01), and the healthy group
      (P<0.01). However, PD is similar in the unaffected hemisphere and healthy group
      (P>0.1). In the small-artery occlusion group, PD in the affected hemisphere was
      similar to that in the contralateral hemisphere (33.8+/-17.9 vs. 32.6+/-21.1
      degree, P>0.1), both sides were significantly lower than the healthy group (all
      P<0.001).The results of the slope of step response agree with the findings in PD.
      CONCLUSIONS: DCA in different subtypes of acute ischemic stroke is heterogeneous,
      which might be attributed to the varied pathologic changes of cerebral blood
      vessels.

PMID- 24671157
TI  - Safety and efficacy using a detachable tip microcatheter in the embolization of
      pediatric arteriovenous malformations.
AB  - PURPOSE: The treatment of deep-seeded pediatric brain arteriovenous malformations
      (AVMs) remains a challenging task. We describe our experience using a new
      detachable tip microcatheter in the embolization of brain arteriovenous
      malformations, pial arteriovenous fistulas, and vein of Galen malformations. We
      describe the safety and efficacy using a new detachable tip microcatheter in the
      treatment of pediatric deep brain arteriovenous malformations, pial
      malformations, and vein of Galen malformations. METHODS: During a period of 9
      months from March 2013 through January 2014, 11 pediatric patients in 14
      procedures with 27 total injections were selected for treatment with a detachable
      tip under Food and Drug Administration (FDA) compassionate use exemption and were
      admitted to our department for treatment of their brain AVM using a liquid
      embolic agent and a detachable tip microcatheter. The ages of the patients ranged
      from 3 months to 18 years old. RESULTS: Of the 27 total injections done, the tip
      detached in seven cases. For the 16 n-BCA injections, the tip detached six times
      (37.5 %), and for the 11 Onyx injections, the tip detached one time (9 %). There
      were no cases of premature microcatheter detachment during normal vessel
      navigation. CONCLUSIONS: The introduction of these detachable tip microcatheters
      allows for a safe and relaxed injection that permits a true circumferential
      occlusion, and may further permit filling a larger amount of angioarchitecture
      without the risk of distal migration, or vessel damage during the usual rapid
      removal of non detachable micocatheters.

PMID- 24671158
TI  - What is the risk of venous infarction to intra-operative sacrifice of either the
      superficial or deep cerebral bridging veins?

PMID- 24671159
TI  - Energy positive domestic wastewater treatment: the roles of anaerobic and
      phototrophic technologies.
AB  - The negative energy balance of wastewater treatment could be reversed if
      anaerobic technologies were implemented for organic carbon oxidation and
      phototrophic technologies were utilized for nutrient recovery. To characterize
      the potential for energy positive wastewater treatment by anaerobic and
      phototrophic biotechnologies we performed a comprehensive literature review and
      analysis, focusing on energy production (as kJ per capita per day and as kJ m(-3)
      of wastewater treated), energy consumption, and treatment efficacy. Anaerobic
      technologies included in this review were the anaerobic baffled reactor (ABR),
      anaerobic membrane bioreactor (AnMBR), anaerobic fluidized bed reactor (AFB),
      upflow anaerobic sludge blanket (UASB), anaerobic sequencing batch reactor
      (ASBR), microbial electrolysis cell (MEC), and microbial fuel cell (MFC).
      Phototrophic technologies included were the high rate algal pond (HRAP),
      photobioreactor (PBR), stirred tank reactor, waste stabilization pond (WSP), and
      algal turf scrubber (ATS). Average energy recovery efficiencies for anaerobic
      technologies ranged from 1.6% (MFC) to 47.5% (ABR). When including typical
      percent chemical oxygen demand (COD) removals by each technology, this range
      would equate to roughly 40-1200 kJ per capita per day or 110-3300 kJ m(-3) of
      treated wastewater. The average bioenergy feedstock production by phototrophic
      technologies ranged from 1200-4700 kJ per capita per day or 3400-13 000 kJ m(-3)
      (exceeding anaerobic technologies and, at times, the energetic content of the
      influent organic carbon), with usable energy production dependent upon downstream
      conversion to fuels. Energy consumption analysis showed that energy positive
      anaerobic wastewater treatment by emerging technologies would require significant
      reductions of parasitic losses from mechanical mixing and gas sparging.
      Technology targets and critical barriers for energy-producing technologies are
      identified, and the role of integrated anaerobic and phototrophic bioprocesses in
      energy positive wastewater management is discussed. 

PMID- 24671161
TI  - Modular hyperthermostable bacterial endo-beta-1,4-mannanase: molecular shape,
      flexibility and temperature-dependent conformational changes.
AB  - Endo-beta-1,4-mannanase from Thermotoga petrophila (TpMan) is a hyperthermostable
      enzyme that catalyzes the hydrolysis of beta-1,4-mannoside linkages in various
      mannan-containing polysaccharides. A recent study reported that TpMan is composed
      of a GH5 catalytic domain joined by a linker to a carbohydrate-binding domain.
      However, at this moment, there is no three-dimensional structure determined for
      TpMan. Little is known about the conformation of the TpMan as well as the role of
      the length and flexibility of the linker on the spatial arrangement of the
      constitutive domains. In this study, we report the first structural
      characterization of the entire TpMan by small-angle X-ray scattering combined
      with the three-dimensional structures of the individual domains in order to shed
      light on the low-resolution model, overall dimensions, and flexibility of this
      modular enzyme at different temperatures. The results are consistent with a
      linker with a compact structure and that occupies a small volume with respect to
      its large number of amino acids. Furthermore, at 20 degrees C the results are
      consistent with a model where TpMan is a molecule composed of three distinct
      domains and that presents some level of molecular flexibility in solution. Even
      though the full enzyme has some degree of molecular flexibility, there might be a
      preferable conformation, which could be described by the rigid-body modeling
      procedure. Finally, the results indicate that TpMan undergoes a temperature
      driven transition between conformational states without a significant disruption
      of its secondary structure. Our results suggest that the linker can optimize the
      geometry between the other two domains with respect to the substrate at high
      temperatures. These studies should provide a useful basis for future biophysical
      studies of entire TpMan. 

PMID- 24671162
TI  - Potential of some yeast strains in the stereoselective synthesis of (R)-(-)
      phenylacetylcarbinol and (S)-(+)-phenylacetylcarbinol and their reduced 1,2
      dialcohol derivatives.
AB  - Whole cells of different yeast species have been widely used for a number of
      asymmetric transformations. In the present study, the screening of several yeast
      strains revealed the utility of Debaryomyces etchellsii in acyloin condensation
      for (R)-(-)-phenylacetylcarbinol production. Some conditions for the efficient
      biotransformation of benzaldehyde and minimization in the production of by
      products were explored: pH of the reaction medium, use of additives (ethanol or
      acetonitrile), temperature, time, and substrate concentration and dosing. The
      optimal conditions found allowed the transformation of up to 10 g/L of the
      starting material in reactions carried out at high scale. Furthermore, the yeast
      Kluyveromyces marxianus was seen to be a convenient biocatalyst to carry out the
      kinetic resolution by the bioreduction of racemic (+/-)-phenylacetylcarbinol,
      resulting in (S)-(+)-phenylacetylcarbinol with excellent stereoselectivity.
      Finally, the ketone reduction of both isolated stereoisomers (R and S) by D.
      etchellsii allowed the obtainment of two of the four diastereoisomers of 1-phenyl
      1,2-propanediol. All these compounds are key precursors for the production of
      interesting pharmaceutical and chemical products. 

PMID- 24671163
TI  - Kinetics of nitrate and sulfate removal using a mixed microbial culture with or
      without limited-oxygen fed.
AB  - The biological degradation of nitrate and sulfate was investigated using a mixed
      microbial culture and lactate as the carbon source, with or without limited
      oxygen fed. It was found that sulfate reduction was slightly inhibited by
      nitrate, since after nitrate depletion the sulfate reduction rate increased from
      0.37 mg SO4 (2-)/mg VSS d to 0.71 mg SO4 (2-)/mg VSS d, and the maximum rate of
      sulfate reduction in the presence of nitrate corresponded to 56 % of the non
      inhibited sulfate reduction rate determined after nitrate depleted. However,
      simultaneous but not sequential reduction of both oxy-anions was observed in this
      study, unlike some literature reports in which sulfate reduction starts only
      after depletion of nitrate, and this case might be due to the fact that lactate
      was always kept above the limiting conditions. At limited oxygen, the inhibited
      effect on sulfate reduction by nitrate was relieved, and the sulfate reduction
      rate seemed relatively higher than that obtained without limited-oxygen fed,
      whereas kept almost constant (0.86-0.89 mg SO4 (2-)/mg VSS d) cross the six ROS
      states. In contrast, nitrate reduction rates decreased substantially with the
      increase in the initial limited-oxygen fed, showing an inhibited effect on
      nitrate reduction by oxygen. Kinetic parameters determined for the mixed
      microbial culture showed that the maximum specific sulfate utilization rate
      obtained (0.098 +/- 0.022 mg SO4 (2-)/(mg VSS h)) was similar to the reported
      typical value (0.1 mg SO4 (2-)/(mg VSS h)), also indicating a moderate inhibited
      effect by nitrate. 

PMID- 24671164
TI  - Microbial community functional structures in wastewater treatment plants as
      characterized by GeoChip.
AB  - BACKGROUND: Biological WWTPs must be functionally stable to continuously and
      steadily remove contaminants which rely upon the activity of complex microbial
      communities. However, knowledge is still lacking in regard to microbial community
      functional structures and their linkages to environmental variables. AIMS: To
      investigate microbial community functional structures of activated sludge in
      wastewater treatment plants (WWTPs) and to understand the effects of
      environmental factors on their structure. METHODS: 12 activated sludge samples
      were collected from four WWTPs in Beijing. A comprehensive functional gene array
      named GeoChip 4.2 was used to determine the microbial functional genes involved
      in a variety of biogeochemical processes such as carbon, nitrogen, phosphorous
      and sulfur cycles, metal resistance, antibiotic resistance and organic
      contaminant degradation. RESULTS: High similarities of the microbial community
      functional structures were found among activated sludge samples from the four
      WWTPs, as shown by both diversity indices and the overlapped genes. For
      individual gene category, such as egl, amyA, lip, nirS, nirK, nosZ, ureC, ppx,
      ppk, aprA, dsrA, sox and benAB, there were a number of microorganisms shared by
      all 12 samples. Canonical correspondence analysis (CCA) showed that the microbial
      functional patterns were highly correlated with water temperature, dissolved
      oxygen (DO), ammonia concentrations and loading rate of chemical oxygen demand
      (COD). Based on the variance partitioning analyses (VPA), a total of 53% of
      microbial community variation from GeoChip data can be explained by wastewater
      characteristics (25%) and operational parameters (23%), respectively.
      CONCLUSIONS: This study provided an overall picture of microbial community
      functional structures of activated sludge in WWTPs and discerned the linkages
      between microbial communities and environmental variables in WWTPs.

PMID- 24671165
TI  - A smartphone application to support recovery from alcoholism: a randomized
      clinical trial.
AB  - IMPORTANCE: Patients leaving residential treatment for alcohol use disorders are
      not typically offered evidence-based continuing care, although research suggests
      that continuing care is associated with better outcomes. A smartphone-based
      application could provide effective continuing care. OBJECTIVE: To determine
      whether patients leaving residential treatment for alcohol use disorders with a
      smartphone application to support recovery have fewer risky drinking days than
      control patients. DESIGN, SETTING, AND PARTICIPANTS: An unmasked randomized
      clinical trial involving 3 residential programs operated by 1 nonprofit treatment
      organization in the Midwestern United States and 2 residential programs operated
      by 1 nonprofit organization in the Northeastern United States. In total, 349
      patients who met the criteria for DSM-IV alcohol dependence when they entered
      residential treatment were randomized to treatment as usual (n = 179) or
      treatment as usual plus a smartphone (n = 170) with the Addiction-Comprehensive
      Health Enhancement Support System (A-CHESS), an application designed to improve
      continuing care for alcohol use disorders. INTERVENTIONS: Treatment as usual
      varied across programs; none offered patients coordinated continuing care after
      discharge. A-CHESS provides monitoring, information, communication, and support
      services to patients, including ways for patients and counselors to stay in
      contact. The intervention and follow-up period lasted 8 and 4 months,
      respectively. MAIN OUTCOMES AND MEASURES: Risky drinking days--the number of days
      during which a patient's drinking in a 2-hour period exceeded 4 standard drinks
      for men and 3 standard drinks for women, with standard drink defined as one that
      contains roughly 14 g of pure alcohol (12 oz of regular beer, 5 oz of wine, or
      1.5 oz of distilled spirits). Patients were asked to report their risky drinking
      days in the previous 30 days on surveys taken 4, 8, and 12 months after discharge
      from residential treatment. RESULTS: For the 8 months of the intervention and 4
      months of follow-up, patients in the A-CHESS group reported significantly fewer
      risky drinking days than did patients in the control group, with a mean of 1.39
      vs 2.75 days (mean difference, 1.37; 95% CI, 0.46-2.27; P = .003). CONCLUSIONS
      AND RELEVANCE: The findings suggest that a multifeatured smartphone application
      may have significant benefit to patients in continuing care for alcohol use
      disorders. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01003119.

PMID- 24671166
TI  - Beyond the volcano limitations in electrocatalysis--oxygen evolution reaction.
AB  - Oxygen evolution catalysis is restricted by the interdependence of adsorption
      energies of the reaction intermediates and the surface reactivity. The
      interdependence reduces the number of degrees of freedom available for catalyst
      optimization. Here it is demonstrated that this limitation can be removed by
      active site modification. This can be achieved on ruthenia by incorporation of Ni
      or Co into the surface, which activates a proton donor-acceptor functionality on
      the conventionally inactive bridge surface sites. This enhances the actual
      measured oxygen evolution activity of the catalyst significantly compared to
      conventional ruthenia. 

PMID- 24671167
TI  - Implantable cardioverter-defibrillator efficacy in Chagas disease patients
      depends not only on the device performance: optimizing the adjunct therapy is
      essential.

PMID- 24671168
TI  - Induced and spontaneous heart rate turbulence in mice: influence of coupling
      interval.
AB  - AIMS: Heart rate turbulence (HRT) is a prognostic parameter for risk
      stratification in patients suffering from coronary artery disease. The aims of
      this study were to demonstrate the feasibility of quantifying HRT in mice, both
      in long-term electrocardiograms (ECGs) as well as after extrastimulus pacing, and
      to analyse its characteristics. METHODS AND RESULTS: We performed long-term ECG
      recordings using implanted telemetric chips and electrophysiological (EP)
      investigations, using transvenously inserted EP catheters, in healthy mice. Heart
      rate turbulence was calculated using the established turbulence onset (TO) and
      slope (TS) algorithm. After spontaneous ventricular premature complexes (VPCs),
      we found a negative TO (-2.2 +/- 7.5%) and positive TS (15.5 +/- 18.3 ms/RR
      interval). Electrophysiological investigations revealed positive values for TO
      (0.6 +/- 1.1%) and TS (6.5 +/- 2.9 ms/RR interval) after extrastimulus pacing
      maneuvers. The shortening of the extrastimuli coupling intervals delivered during
      EP investigations significantly influenced TO (r = 0.57; P = 0.01): shorter
      coupling intervals provoked more positive TO values. CONCLUSION: Mice display
      both spontaneous and induced HRT. In terms of TO, VPCs generated by extrastimulus
      pacing are significantly dependent on the coupling interval. Determining HRT in
      mice is feasible and provides insight into basic mechanisms of blood pressure
      regulation, which is realized by the baroreflex.

PMID- 24671171
TI  - Exciton diffusion in monolayer and bulk MoSe2.
AB  - The exciton dynamics in monolayer and bulk MoSe2 samples are studied by transient
      absorption microscopy with a high spatiotemporal resolution. Excitons are
      injected with a point-like spatial distribution using a tightly focused
      femtosecond pulse. The spatiotemporal dynamics of these excitons are monitored by
      measuring transient absorption of a time-delayed and spatially scanned probe
      pulse. We obtain the exciton diffusion coefficients of 12 +/- 3 and 19 +/- 2
      cm(2) s(-1) and exciton lifetimes of 130 +/- 20 and 210 +/- 10 ps in the
      monolayer and bulk samples, respectively. These values are useful for
      understanding excitons and their interactions with the environment in these
      structures and potential applications of MoSe2 in optoelectronics and
      electronics. 

PMID- 24671169
TI  - Activation of nucleotide oligomerization domain 2 (NOD2) by human cytomegalovirus
      initiates innate immune responses and restricts virus replication.
AB  - Nucleotide-binding oligomerization domain 2 (NOD2) is an important innate immune
      sensor of bacterial pathogens. Its induction results in activation of the classic
      NF-kappaB pathway and alternative pathways including type I IFN and autophagy.
      Although the importance of NOD2 in recognizing RNA viruses has recently been
      identified, its role in sensing DNA viruses has not been studied. We report that
      infection with human cytomegalovirus (HCMV) results in significant induction of
      NOD2 expression, beginning as early as 2 hours post infection and increasing
      steadily 24 hours post infection and afterwards. Infection with human herpesvirus
      1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is
      not required for NOD2 induction, a replication competent virion is necessary.
      Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs) and U373
      glioma cells leads to enhanced HCMV replication along with decreased levels of
      interferon beta (IFN-beta) and the pro-inflammatory cytokine, IL8. NOD2 induction
      in HCMV-infected cells activates downstream NF-kappaB and interferon pathways
      supported by reduced nuclear localization of NF-kappaB and pIRF3 in NOD2
      knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication
      in association with increased levels of IFN-beta and IL8. Similarly, transient
      overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in
      decreased HCMV replication and enhanced cytokine responses. However,
      overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's
      disease, results in enhanced HCMV replication and decreased levels of IFN-beta in
      U373 cells. These results show for the first time that NOD2 plays a significant
      role in HCMV replication and may provide a model for studies of HCMV recognition
      by the host cell and HCMV colitis in Crohn's disease. 

PMID- 24671170
TI  - Bringing the cognitive estimation task into the 21st century: normative data on
      two new parallel forms.
AB  - The Cognitive Estimation Test (CET) is widely used by clinicians and researchers
      to assess the ability to produce reasonable cognitive estimates. Although several
      studies have published normative data for versions of the CET, many of the items
      are now outdated and parallel forms of the test do not exist to allow cognitive
      estimation abilities to be assessed on more than one occasion. In the present
      study, we devised two new 9-item parallel forms of the CET. These versions were
      administered to 184 healthy male and female participants aged 18-79 years with 9
      22 years of education. Increasing age and years of education were found to be
      associated with successful CET performance as well as gender, intellect, naming,
      arithmetic and semantic memory abilities. To validate that the parallel forms of
      the CET were sensitive to frontal lobe damage, both versions were administered to
      24 patients with frontal lobe lesions and 48 age-, gender- and education-matched
      controls. The frontal patients' error scores were significantly higher than the
      healthy controls on both versions of the task. This study provides normative data
      for parallel forms of the CET for adults which are also suitable for assessing
      frontal lobe dysfunction on more than one occasion without practice effects. 

PMID- 24671172
TI  - Rubber hand illusion affects joint angle perception.
AB  - The Rubber Hand Illusion (RHI) is a well-established experimental paradigm. It
      has been shown that the RHI can affect hand location estimates, arm and hand
      motion towards goals, the subjective visual appearance of the own hand, and the
      feeling of body ownership. Several studies also indicate that the peri-hand space
      is partially remapped around the rubber hand. Nonetheless, the question remains
      if and to what extent the RHI can affect the perception of other body parts. In
      this study we ask if the RHI can alter the perception of the elbow joint.
      Participants had to adjust an angular representation on a screen according to
      their proprioceptive perception of their own elbow joint angle. The results show
      that the RHI does indeed alter the elbow joint estimation, increasing the
      agreement with the position and orientation of the artificial hand. Thus, the
      results show that the brain does not only adjust the perception of the hand in
      body-relative space, but it also modifies the perception of other body parts. In
      conclusion, we propose that the brain continuously strives to maintain a
      consistent internal body image and that this image can be influenced by the
      available sensory information sources, which are mediated and mapped onto each
      other by means of a postural, kinematic body model. 

PMID- 24671173
TI  - Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced
      lung inflammation in CFTR-deficient mice.
AB  - CFTR (cystic fibrosis transmembrane conductance regulator) is expressed by both
      neutrophils and platelets. Lack of functional CFTR could lead to severe lung
      infection and inflammation. Here, we found that mutation of CFTR (F508del) or
      inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar
      neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory
      protein-2) or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage)
      during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2
      production in LPS-stimulated neutrophils; however, lipoxin A4 could dose
      dependently suppress this effect. In LPS-induced acute lung inflammation,
      blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism
      of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could
      significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype
      mice. Concurrently, F508del mice had higher plasma platelet activating factor
      (PAF) levels and PAF-AH activity compared to wildtype under LPS challenge.
      Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase)
      inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice
      compared to vehicle treated F508del group. Particularly, depletion of platelets
      in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH
      activity and deteriorate LPS-induced lung inflammation compared to control
      F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS
      induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and
      PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated
      lung inflammation. 

PMID- 24671174
TI  - Face recognition increases during saccade preparation.
AB  - Face perception is integral to human perception system as it underlies social
      interactions. Saccadic eye movements are frequently made to bring interesting
      visual information, such as faces, onto the fovea for detailed processing. Just
      before eye movement onset, the processing of some basic features, such as the
      orientation, of an object improves at the saccade landing point. Interestingly,
      there is also evidence that indicates faces are processed in early visual
      processing stages similar to basic features. However, it is not known whether
      this early enhancement of processing includes face recognition. In this study,
      three experiments were performed to map the timing of face presentation to the
      beginning of the eye movement in order to evaluate pre-saccadic face recognition.
      Faces were found to be similarly processed as simple objects immediately prior to
      saccadic movements. Starting ~ 120 ms before a saccade to a target face,
      independent of whether or not the face was surrounded by other faces, the face
      recognition gradually improved and the critical spacing of the crowding decreased
      as saccade onset was approaching. These results suggest that an upcoming saccade
      prepares the visual system for new information about faces at the saccade landing
      site and may reduce the background in a crowd to target the intended face. This
      indicates an important role of pre-saccadic eye movement signals in human face
      recognition. 

PMID- 24671175
TI  - Combining genomic and genealogical information in a reproducing kernel Hilbert
      spaces regression model for genome-enabled predictions in dairy cattle.
AB  - Genome-enhanced genotypic evaluations are becoming popular in several livestock
      species. For this purpose, the combination of the pedigree-based relationship
      matrix with a genomic similarities matrix between individuals is a common
      approach. However, the weight placed on each matrix has been so far established
      with ad hoc procedures, without formal estimation thereof. In addition, when
      using marker- and pedigree-based relationship matrices together, the resulting
      combined relationship matrix needs to be adjusted to the same scale in reference
      to the base population. This study proposes a semi-parametric Bayesian method for
      combining marker- and pedigree-based information on genome-enabled predictions. A
      kernel matrix from a reproducing kernel Hilbert spaces regression model was used
      to combine genomic and genealogical information in a semi-parametric scenario,
      avoiding inversion and adjustment complications. In addition, the weights on
      marker- versus pedigree-based information were inferred from a Bayesian model
      with Markov chain Monte Carlo. The proposed method was assessed involving a large
      number of SNPs and a large reference population. Five phenotypes, including
      production and type traits of dairy cattle were evaluated. The reliability of the
      genome-based predictions was assessed using the correlation, regression
      coefficient and mean squared error between the predicted and observed values. The
      results indicated that when a larger weight was given to the pedigree-based
      relationship matrix the correlation coefficient was lower than in situations
      where more weight was given to genomic information. Importantly, the posterior
      means of the inferred weight were near the maximum of 1. The behavior of the
      regression coefficient and the mean squared error was similar to the performance
      of the correlation, that is, more weight to the genomic information provided a
      regression coefficient closer to one and a smaller mean squared error. Our
      results also indicated a greater accuracy of genomic predictions when using a
      large reference population. 

PMID- 24671177
TI  - Measuring the value of research data: a citation analysis of oceanographic data
      sets.
AB  - Evaluation of scientific research is becoming increasingly reliant on publication
      based bibliometric indicators, which may result in the devaluation of other
      scientific activities--such as data curation--that do not necessarily result in
      the production of scientific publications. This issue may undermine the movement
      to openly share and cite data sets in scientific publications because researchers
      are unlikely to devote the effort necessary to curate their research data if they
      are unlikely to receive credit for doing so. This analysis attempts to
      demonstrate the bibliometric impact of properly curated and openly accessible
      data sets by attempting to generate citation counts for three data sets archived
      at the National Oceanographic Data Center. My findings suggest that all three
      data sets are highly cited, with estimated citation counts in most cases higher
      than 99% of all the journal articles published in Oceanography during the same
      years. I also find that methods of citing and referring to these data sets in
      scientific publications are highly inconsistent, despite the fact that a formal
      citation format is suggested for each data set. These findings have important
      implications for developing a data citation format, encouraging researchers to
      properly curate their research data, and evaluating the bibliometric impact of
      individuals and institutions.

PMID- 24671176
TI  - Allergic airway inflammation by nasal inoculation of particulate matter (PM2.5)
      in NC/Nga mice.
AB  - To evaluate the effect of airborne particulate matter 2.5 (PM2.5) in winter on
      airway inflammation, water-soluble supernatant (Sup) and water-insoluble
      precipitate (Pre) in PM2.5 were inoculated in NC/Nga mice with high sensitivity
      to mite allergens. Sup with aluminum oxide was injected intraperitoneally for
      sensitization. Five days later, Sup, Pre or both Sup and Pre were inoculated via
      the nasal route five times for more sensitization and a challenge inoculation on
      the 11th day in NC/Nga mice. On the 12th day, mice were examined for airway
      hyperresponsiveness (AHR), BALF cell count and IL-1beta concentration, mRNA
      expression of Th1 and Th2 cytokines, chemokines such as eotaxin 1 and eotaxin 2,
      inflammasomal complex molecules such as IL-1beta, caspase 1 and the nucleotide
      binding domain and leucine-rich repeat protein 3 (NLRP3) in lung tissue as well
      as histopathology. The synergistic effect of Sup and Pre was observed in terms of
      increases in AHR, BALF cells, the mRNA expression of IL-13, eotaxin1 and IL
      1beta, and the IL-1beta concentration in BALF. Intracellular deposits of
      insoluble particulates were observed in macrophages around inflammatory
      granulation of the mouse group treated with Sup and Pre. These results suggest
      that PM2.5 can induce airway hyperresponsiveness in mice with genetically high
      sensitivity to mite allergens by an inflammasome-associated mechanism and
      synergistic action of insoluble particulates and soluble components. 

PMID- 24671178
TI  - Deep belief networks learn context dependent behavior.
AB  - With the goal of understanding behavioral mechanisms of generalization, we
      analyzed the ability of neural networks to generalize across context. We modeled
      a behavioral task where the correct responses to a set of specific sensory
      stimuli varied systematically across different contexts. The correct response
      depended on the stimulus (A,B,C,D) and context quadrant (1,2,3,4). The possible
      16 stimulus-context combinations were associated with one of two responses (X,Y),
      one of which was correct for half of the combinations. The correct responses
      varied symmetrically across contexts. This allowed responses to previously unseen
      stimuli (probe stimuli) to be generalized from stimuli that had been presented
      previously. By testing the simulation on two or more stimuli that the network had
      never seen in a particular context, we could test whether the correct response on
      the novel stimuli could be generated based on knowledge of the correct responses
      in other contexts. We tested this generalization capability with a Deep Belief
      Network (DBN), Multi-Layer Perceptron (MLP) network, and the combination of a DBN
      with a linear perceptron (LP). Overall, the combination of the DBN and LP had the
      highest success rate for generalization. 

PMID- 24671179
TI  - Attitudes of medical students towards conflict of interest: a national survey in
      France.
AB  - Following recent health scandals in France, the French parliament adopted law n
      degrees 2011-2012 to regulate ties between physicians and the pharmaceutical
      industry. The law also requires pharmaceutical companies to publicize financial
      and other benefits given to medical students. In this context, we administered a
      survey to medical students in France, in an effort to identify priorities for
      future education regarding conflicts of interest (COI). This web-based survey
      encompassed knowledge about, training on, personal exposure to, and opinions on
      COI among preclinical and clinical students as well as residents. Two thousand
      one hundred and one (2,101) students participated. Although most students (64.6%)
      believed that they are able to define what a COI is, they failed to correctly
      identify several situations as COI (receiving a gift, being offered a meal, being
      invited to a conference). Most students reported feeling inadequately educated
      about COI (85.2%). Compared to other class levels, residents were more exposed to
      pharmaceutical sales representatives. This exposure is highly associated to
      receipt of gifts (OR 14.51, 95% CI 11.67-18.05). Medical students were aware of
      potential bias induced by COI with respect to drug prescriptions and research,
      but felt personally immune towards COI. In our survey, personal research
      performed by students was more likely to be associated with perception of
      potential bias on prescription for self (but not for others) than attending a
      lecture on COI. Promulgating laws that regulate ties between physicians/students
      and the pharmaceutical industry is a mandatory first step. However, complementary
      strategies should be implemented within medical schools, in particular, specific
      training about COI in early medical education. 

PMID- 24671180
TI  - 9-cis-retinoic Acid and troglitazone impacts cellular adhesion, proliferation,
      and integrin expression in K562 cells.
AB  - Retinoids are established pleiotropic regulators of both adaptive and innate
      immune responses. Recently, troglitazone, a PPAR gamma agonist, has been
      demonstrated to have anti-inflammatory effects. Separately, retinoids and
      troglitazone are implicated in immune related processes; however, their
      combinatory role in cellular adhesion and proliferation has not been well
      established. In this study, the effect of 9-cis-retinoic acid (9-cis-RA) and
      troglitazone on K562 cellular adhesion and proliferation was investigated.
      Troglitazone exposure decreased K562 cellular adhesion to RGD containing
      extracellular matrix proteins fibronectin, FN-120, and vitronectin in a
      concentration and time-dependent manner. In the presence of troglitazone, 9-cis
      retinoic acid restores cellular adhesion to levels comparable to vehicle
      treatment alone on fibronectin, FN-120, and vitronectin substrates within 72
      hours. Due to the prominent role of integrins in attachment to extracellular
      matrix proteins, we evaluated the level of integrin alpha5 subunit expression.
      Troglitazone treatment results in decrease in alpha5 subunit expression on the
      cell surface. In the presence of both agonists, cell surface alpha5 subunit
      expression was restored to levels comparable to vehicle treatment alone.
      Additionally, troglitazone and 9-cis-RA mediated cell adhesion was decreased in
      the presence of a function blocking integrin alpha 5 inhibitor. Further, through
      retinoid metabolic profiling and HPLC analysis, our study demonstrates that
      troglitazone augments retinoid availability in K562 cells. Finally, we
      demonstrate that troglitazone and 9-cis-retinoic acid synergistically dampen
      cellular proliferation in K562 cells. Our study is the first to report that the
      combination of troglitazone and 9-cis-retinoic acid restores cellular adhesion,
      alters retinoid availability, impacts integrin expression, and dampens cellular
      proliferation in K562 cells. 

PMID- 24671181
TI  - Does dexmedetomidine as a neuraxial adjuvant facilitate better anesthesia and
      analgesia? A systematic review and meta-analysis.
AB  - BACKGROUND: Neuraxial application of dexmedetomidine (DEX) as adjuvant analgesic
      has been invetigated in some randomized controlled trials (RCTs) but not been
      approved because of the inconsistency of efficacy and safety in these RCTs. We
      performed this meta-analysis to access the efficacy and safety of neuraxial DEX
      as local anaesthetic (LA) adjuvant. METHODS: We searched PubMed, PsycINFO,
      Scopus, EMBASE, and CENTRAL databases from inception to June 2013 for RCTs that
      investigated the analgesia efficacy and safety for neuraxial application DEX as
      LA adjuvant. Effects were summarized using standardized mean differences (SMDs),
      weighed mean differences (WMDs) or odds ratio (OR) with suitable effect model.
      The primary outcomes were postoperative pain intensity and analgesic duration,
      bradycardia and hypotension. RESULTS: Sixteen RCTs involving 1092 participants
      were included. Neuraxial DEX significantly decreased postoperative pain intensity
      (SMD, -1.29; 95% confidence interval (CI), -1.70 to -0.89; P<0.00001), prolonged
      analgesic duration (WMD, 6.93 hours; 95% CI, 5.23 to 8.62; P<0.00001) and
      increased the risk of bradycardia (OR, 2.68; 95% CI, 1.18 to 6.10; P = 0.02). No
      evidence showed that neuraxial DEX increased the risk of other adverse events,
      such as hypotension (OR, 1.54; 95% CI, 0.83 to 2.85; P = 0.17). Additionally,
      neuraxial DEX was associated with beneficial alterations in postoperative
      sedation scores and number of analgesic requirements, sensory and motor block
      characteristics, and intro-operative hemodynamics. CONCLUSION: Neuraxial DEX is a
      favorable LA adjuvant with better and longer analgesia. The greatest concern is
      bradycardia. Further large sample trials with strict design and focusing on long
      term outcomes are needed.

PMID- 24671182
TI  - Independent polled mutations leading to complex gene expression differences in
      cattle.
AB  - The molecular regulation of horn growth in ruminants is still poorly understood.
      To investigate this process, we collected 1019 hornless (polled) animals from
      different cattle breeds. High-density SNP genotyping confirmed the presence of
      two different polled associated haplotypes in Simmental and Holstein cattle co
      localized on BTA 1. We refined the critical region of the Simmental polled
      mutation to 212 kb and identified an overlapping region of 932 kb containing the
      Holstein polled mutation. Subsequently, whole genome sequencing of polled
      Simmental and Holstein cows was used to determine polled associated genomic
      variants. By genotyping larger cohorts of animals with known horn status we found
      a single perfectly associated insertion/deletion variant in Simmental and other
      beef cattle confirming the recently published possible Celtic polled mutation. We
      identified a total of 182 sequence variants as candidate mutations for polledness
      in Holstein cattle, including an 80 kb genomic duplication and three SNPs
      reported before. For the first time we showed that hornless cattle with scurs are
      obligate heterozygous for one of the polled mutations. This is in contrast to
      published complex inheritance models for the bovine scurs phenotype. Studying
      differential expression of the annotated genes and loci within the mapped region
      on BTA 1 revealed a locus (LOC100848215), known in cow and buffalo only, which is
      higher expressed in fetal tissue of wildtype horn buds compared to tissue of
      polled fetuses. This implicates that the presence of this long noncoding RNA is a
      prerequisite for horn bud formation. In addition, both transcripts associated
      with polledness in goat and sheep (FOXL2 and RXFP2), show an overexpression in
      horn buds confirming their importance during horn development in cattle. 

PMID- 24671183
TI  - Mechanistic insights into the gold chemistry of allenes.
AB  - Although most mechanistic studies on gold-catalysed reactions focused on alkynes
      as substrates, some knowledge about gold-catalysed conversions of allenic
      substrates has been obtained. This contribution summarises these insights into
      the reaction mechanisms of gold-catalysed transformations of allenes which are
      based on computational studies, labelling studies, the detection of
      intermediates, chirality transfer and diastereoselective product formation. 

PMID- 24671184
TI  - Phenotypic and genotypic characteristics of novel mouse cell line (NIH/3T3)
      adapted human enterovirus 71 strains (EV71:TLLm and EV71:TLLmv).
AB  - Since its identification in 1969, Enterovirus 71 (EV71) has been causing periodic
      outbreaks of infection in children worldwide and most prominently in the Asia
      Pacific Region. Understanding the pathogenesis of Enterovirus 71 (EV71) is
      hampered by the virus's inability to infect small animals and replicate in their
      derived in vitro cultured cells. This manuscript describes the phenotypic and
      genotypic characteristics of two selected EV71 strains (EV71:TLLm and
      EV71:TLLmv), which have been adapted to replicate in mouse-derived NIH/3T3 cells,
      in contrast to the original parental virus which is only able to replicate in
      primate cell lines. The EV71:TLLm strain exhibited productive infection in all
      primate and rodent cell lines tested, while EV71:TLLmv exhibited greater
      preference for mouse cell lines. EV71:TLLmv displayed higher degree of adaptation
      and temperature adaptability in NIH/3T3 cells than in Vero cells, suggesting much
      higher fitness in NIH/3T3 cells. In comparison with the parental EV71:BS strain,
      the adapted strains accumulated multiple adaptive mutations in the genome
      resulting in amino acid substitutions, most notably in the capsid-encoding region
      (P1) and viral RNA-dependent RNA polymerase (3D). Two mutations, E167D and L169F,
      were mapped to the VP1 canyon that binds the SCARB2 receptor on host cells.
      Another two mutations, S135T and K140I, were located in the VP2 neutralization
      epitope spanning amino acids 136-150. This is the first report of human EV71 with
      the ability to productively infect rodent cell lines in vitro. 

PMID- 24671185
TI  - The beginning of metallurgy in the southern Levant: a late 6th millennium CalBC
      copper awl from Tel Tsaf, Israel.
AB  - The beginning of metallurgy in the ancient Near East attracts much attention. The
      southern Levant, with the rich assemblage of copper artifacts from the Nahal
      Mishmar cave and the unique gold rings of the Nahal Qanah cave, is regarded as a
      main center of early metallurgy during the second half of the 5th millennium
      CalBC. However, a recently discovered copper awl from a Middle Chalcolithic
      burial at Tel Tsaf, Jordan Valley, Israel, suggests that cast metal technology
      was introduced to the region as early as the late 6th millennium CalBC. This
      paper examines the chemical composition of this item and reviews its context. The
      results indicate that it was exported from a distant source, probably in the
      Caucasus, and that the location where it was found is indicative of the social
      status of the buried individual. This rare finding indicates that metallurgy was
      first diffused [corrected] to the southern Levant through exchange networks and
      only centuries later involved local productionThis copper awl, the earliest metal
      artifact found in the southern Levant, indicates that the elaborate Late
      Chalcolithic metallurgy developed from a more ancient tradition.

PMID- 24671186
TI  - Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer:
      pathological implications in diagnosis.
AB  - PURPOSE: Radical changes in both expression and glycosylation pattern of
      transmembrane mucins have been observed in various malignancies. We and others
      have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in
      cell signaling events that drive several epithelial malignancies. In the present
      study, we investigated the expression profile of MUC1 and MUC4 in the non
      neoplastic bladder urothelium, in various malignant neoplasms of bladder and in
      bladder carcinoma cell lines. MATERIAL AND METHODS: Immunohistochemistry was
      performed on tissue sections from the urinary bladder biopsies, resection samples
      and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and
      MUC4. We also investigated their expression in bladder carcinoma cell lines by RT
      PCR and immunoblotting. RESULTS: MUC1 is expressed on the apical surface or in
      umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression
      of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased
      from normal urothelium (n = 27, 0.35+/-0.12) to urothelial carcinoma (UC, n =
      323, H-score, 2.4+/-0.22, p<=0.0001). In contrast to MUC1, MUC4 was expressed in
      all the layers of non-neoplastic bladder urothelium (n = 14, 2.5+/-0.28), both in
      the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the
      loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56+/
      0.06). However, re-expression of MUC4 was observed in a subset of metastatic
      cases of urothelial carcinoma (mean H-score 0.734+/-0.9). CONCLUSION: The
      expression of MUC1 is increased while that of MUC4 decreased in UC compared to
      the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however,
      are significantly higher in urothelial carcinoma metastatic cases compared to
      localized UC. These results suggest differential expression of MUC1 and MUC4
      during development and progression of bladder carcinoma.

PMID- 24671187
TI  - Gene and protein expression in response to different growth temperatures and
      oxygen availability in Burkholderia thailandensis.
AB  - Burkholderia thailandensis, although normally avirulent for mammals, can infect
      macrophages in vitro and has occasionally been reported to cause pneumonia in
      humans. It is therefore used as a model organism for the human pathogen B.
      pseudomallei, to which it is closely related phylogenetically. We characterized
      the B. thailandensis clinical isolate CDC2721121 (BtCDC272) at the genome level
      and studied its response to environmental cues associated with human host
      colonization, namely, temperature and oxygen limitation. Effects of the different
      growth conditions on BtCDC272 were studied through whole genome transcription
      studies and analysis of proteins associated with the bacterial cell surface. We
      found that growth at 37 degrees C, compared to 28 degrees C, negatively affected
      cell motility and flagella production through a mechanism involving regulation of
      the flagellin-encoding fliC gene at the mRNA stability level. Growth in oxygen
      limiting conditions, in contrast, stimulated various processes linked to
      virulence, such as lipopolysaccharide production and expression of genes encoding
      protein secretion systems. Consistent with these observations, BtCDC272 grown in
      oxygen limitation was more resistant to phagocytosis and strongly induced the
      production of inflammatory cytokines from murine macrophages. Our results suggest
      that, while temperature sensing is important for regulation of B. thailandensis
      cell motility, oxygen limitation has a deeper impact on its physiology and
      constitutes a crucial environmental signal for the production of virulence
      factors. 

PMID- 24671188
TI  - Designing a high-throughput somatic mutation profiling panel specifically for
      gynaecological cancers.
AB  - Somatic mutations play a major role in tumour initiation and progression. The
      mutation status of a tumour may predict prognosis and guide targeted therapies.
      The majority of techniques to study oncogenic mutations require high quality and
      quantity DNA or are analytically challenging. Mass-spectrometry based mutation
      analysis however is a relatively simple and high-throughput method suitable for
      formalin-fixed, paraffin-embedded (FFPE) tumour material. Targeted gene panels
      using this technique have been developed for several types of cancer. These
      current cancer hotspot panels are not focussed on the genes that are most
      relevant in gynaecological cancers. In this study, we report the design and
      validation of a novel, mass-spectrometry based panel specifically for
      gynaecological malignancies and present the frequencies of detected mutations.
      Using frequency data from the online Catalogue of Somatic Mutations in Cancer, we
      selected 171 somatic hotspot mutations in the 13 most important genes for
      gynaecological cancers, being BRAF, CDKN2A, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2,
      HRAS, KRAS, NRAS, PIK3CA, PPP2R1A and PTEN. A total of 546 tumours (205 cervical,
      227 endometrial, 89 ovarian, and 25 vulvar carcinomas) were used to test and
      validate our panel, and to study the prevalence and spectrum of somatic mutations
      in these types of cancer. The results were validated by testing duplicate samples
      and by allele-specific qPCR. The panel presented here using mass-spectrometry
      shows to be reproducible and high-throughput, and is usefull in FFPE material of
      low quality and quantity. It provides new possibilities for studying large
      numbers of gynaecological tumour samples in daily practice, and could be useful
      in guided therapy selection. 

PMID- 24671190
TI  - A prospective study of breast dynamic morphological changes after dual-plane
      augmentation mammaplasty with 3D scanning technique.
AB  - BACKGROUND: The dual-plane technique has been widely used in augmentation
      mammaplasty procedures. However, there are some concerns about aesthetic contour
      maintenance for long time after muscle releasing. This study aims to track and
      analyze breast dynamic morphological changes after dual-plane breast augmentation
      with three-dimensional (3D) scanning technique. METHODS: Thirteen dual-plane
      anatomic implant augmentation patients underwent 3D scanning preoperatively (pre
      OP) and postoperatively in four time points (1 month: post-1M, 3 months: post-3M,
      6 months: post-6M and 12 months: post-12M). The linear distance, breast
      projection, nipple position, breast volume and breast surface area were measured
      and analyzed on the 3D models over time. RESULTS: Compared with post-12M, no
      significant differences were found in distances of nipple to midline, nipple to
      inframammary fold and sternal notch to the level of inframammary fold after 6
      months in both straight-line distance and its projection on surface. The
      distances between sternal notch and nipple had no significant difference after
      post-1M. Breast volume changes had no significant difference after post-3M. The
      volume and area percentage of upper pole decreased while the lower pole's
      increased gradually. The surface showed no significant changes after post-1M. The
      changes of breast projection had no significance after post-1M either. The nipple
      moved 1.0+/-0.6 cm laterally (X axis), 0.6+/-0.7 cm upward( Y axis) and 2.3+/-1.1
      cm anteriorly (Z axis) at post-12M, and the differences were not significant
      after post-1M. CONCLUSIONS: 3D scanning technique provides an objective and
      effective way to evaluate breast morphological changes after augmentation
      mammaplasty over time. Dual-plane augmentation optimizes breast shape especially
      in the lower pole and maintains stable aesthetic outcome during the 12 months
      follow-up. Most of the contour changes and the interadaptation with the implant
      have completed 6 months after operation. Therefore, 6 months could be chosen as a
      relatively stable observing period in the assessment of postoperative outcomes of
      dual-plane breast augmentation.

PMID- 24671191
TI  - Melanopsin ganglion cells are the most resistant retinal ganglion cell type to
      axonal injury in the rat retina.
AB  - We report that the most common retinal ganglion cell type that remains after
      optic nerve transection is the M1 melanopsin ganglion cell. M1 ganglion cells are
      members of the intrinsically photosensitive retinal ganglion cell population that
      mediates non-image-forming vision, comprising ~2.5% of all ganglion cells in the
      rat retina. In the present study, M1 ganglion cells comprised 1.7+/-1%, 28+/-14%,
      55+/-13% and 82+/-8% of the surviving ganglion cells 7, 14, 21 and 60 days after
      optic nerve transection, respectively. Average M1 ganglion cell somal diameter
      and overall morphological appearance remained unchanged in non-injured and
      injured retinas, suggesting a lack of injury-induced degeneration. Average M1
      dendritic field size increased at 7 and 60 days following optic nerve
      transection, while average dendritic field size remained similar in non-injured
      retinas and in retinas at 14 and 21 days after optic nerve transection. These
      findings demonstrate that M1 ganglion cells are more resistant to injury than
      other ganglion cell types following optic nerve injury, and provide an
      opportunity to develop pharmacological or genetic therapeutic approaches to
      mitigate ganglion cell death and save vision following optic nerve injury. 

PMID- 24671193
TI  - Role of nitric oxide synthases in early blood-brain barrier disruption following
      transient focal cerebral ischemia.
AB  - The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB)
      disruption was determined using a new mouse model of transient focal cerebral
      ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at
      its M2 segment and reperfusion was induced by releasing the ligation. The
      diameter alteration of the MCA, arterial anastomoses and collateral arteries were
      imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB)
      and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The
      reperfusion produced an extensive vasodilation and a sustained hyperemia.
      Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a
      non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia
      and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS
      (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB
      disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly
      reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine
      (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral
      vasodilation or BBB disruption. On the other hand, papaverine (PV) not only
      increased the vasodilation/hyperemia but also significantly reduced BBB
      disruption. Combined treatment with L-NAME and PV preserved the
      vasodilation/hyperemia and significantly reduced BBB disruption. Our findings
      suggest that nNOS may play a major role in early BBB disruption following
      transient focal cerebral ischemia via a hyperemia-independent mechanism. 

PMID- 24671194
TI  - Comparisons of native Shiga toxins (Stxs) type 1 and 2 with chimeric toxins
      indicate that the source of the binding subunit dictates degree of toxicity.
AB  - Shiga toxin (Stx)-producing E. coli (STEC) cause food-borne outbreaks of
      hemorrhagic colitis. The main virulence factor expressed by STEC, Stx, is an AB5
      toxin that has two antigenically distinct forms, Stx1a and Stx2a. Although Stx1a
      and Stx2a bind to the same receptor, globotriaosylceramide (Gb3), Stx2a is more
      potent than Stx1a in mice, whereas Stx1a is more cytotoxic than Stx2a in cell
      culture. In this study, we used chimeric toxins to ask what the relative
      contribution of individual Stx subunits is to the differential toxicity of Stx1a
      and Stx2a in vitro and in vivo. Chimeric stx1/stx2 operons were generated by PCR
      such that the coding regions for the A2 and B subunits of one toxin were combined
      with the coding region for the A1 subunit of the heterologous toxin. The
      toxicities of purified Stx1a, Stx2a, and the chimeric Stxs were determined on
      Vero and HCT-8 cell lines, while polarized HCT-8 cell monolayers grown on
      permeable supports were used to follow toxin translocation. In all in vitro
      assays, the activity of the chimeric toxin correlated with that of the parental
      toxin from which the B subunit originated. The origin of the native B subunit
      also dictated the 50% lethal dose of toxin after intraperitoneal intoxication of
      mice; however, the chimeric Stxs exhibited reduced oral toxicity and pH stability
      compared to Stx1a and Stx2a. Taken together, these data support the hypothesis
      that the differential toxicity of the chimeric toxins for cells and mice is
      determined by the origin of the B subunit. 

PMID- 24671195
TI  - Does encapsulation protect embryos from the effects of ocean acidification? The
      example of Crepidula fornicata.
AB  - Early life history stages of marine organisms are generally thought to be more
      sensitive to environmental stress than adults. Although most marine invertebrates
      are broadcast spawners, some species are brooders and/or protect their embryos in
      egg or capsules. Brooding and encapsulation strategies are typically assumed to
      confer greater safety and protection to embryos, although little is known about
      the physico-chemical conditions within egg capsules. In the context of ocean
      acidification, the protective role of encapsulation remains to be investigated.
      To address this issue, we conducted experiments on the gastropod Crepidula
      fornicata. This species broods its embryos within capsules located under the
      female and veliger larvae are released directly into the water column. C.
      fornicata adults were reared at the current level of CO2 partial pressure (pCO2)
      (390 MUatm) and at elevated levels (750 and 1400 MUatm) before and after
      fertilization and until larval release, such that larval development occurred
      entirely at a given pCO2. The pCO2 effects on shell morphology, the frequency of
      abnormalities and mineralization level were investigated on released larvae.
      Shell length decreased by 6% and shell surface area by 11% at elevated pCO2 (1400
      MUatm). The percentage of abnormalities was 1.5- to 4-fold higher at 750 MUatm
      and 1400 MUatm pCO2, respectively, than at 390 MUatm. The intensity of
      birefringence, used as a proxy for the mineralization level of the larval shell,
      also decreased with increasing pCO2. These negative results are likely explained
      by increased intracapsular acidosis due to elevated pCO2 in extracapsular
      seawater. The encapsulation of C. fornicata embryos did not protect them against
      the deleterious effects of a predicted pCO2 increase. Nevertheless, C. fornicata
      larvae seemed less affected than other mollusk species. Further studies are
      needed to identify the critical points of the life cycle in this species in light
      of future ocean acidification. 

PMID- 24671199
TI  - Increased flight altitudes among migrating golden eagles suggest turbine
      avoidance at a Rocky Mountain wind installation.
AB  - Potential wind-energy development in the eastern Rocky Mountain foothills of
      British Columbia, Canada, raises concerns due to its overlap with a golden eagle
      (Aquila chrysaetos) migration corridor. The Dokie 1 Wind Energy Project is the
      first development in this area and stands as a model for other projects in the
      area because of regional consistency in topographic orientation and weather
      patterns. We visually tracked golden eagles over three fall migration seasons
      (2009-2011), one pre- and two post-construction, to document eagle flight
      behaviour in relation to a ridge-top wind energy development. We estimated three
      dimensional positions of eagles in space as they migrated through our study site.
      Flight tracks were then incorporated into GIS to ascertain flight altitudes for
      eagles that flew over the ridge-top area (or turbine string). Individual flight
      paths were designated to a category of collision-risk based on flight altitude
      (e.g. flights within rotor-swept height; <=150 m above ground) and wind speed
      (winds sufficient for the spinning of turbines; >6.8 km/h at ground level).
      Eagles were less likely to fly over the ridge-top area within rotor-swept height
      (risk zone) as wind speed increased, but were more likely to make such crosses
      under headwinds and tailwinds compared to western crosswinds. Most importantly,
      we observed a smaller proportion of flights within the risk zone at wind speeds
      sufficient for the spinning of turbines (higher-risk flights) during post
      construction compared to pre-construction, suggesting that eagles showed
      detection and avoidance of turbines during migration. 

PMID- 24671197
TI  - The association between adiposity, mental well-being, and quality of life in
      extreme obesity.
AB  - OBJECTIVES: To explore the cross-sectional association between adiposity, mental
      well-being, and quality of life in extreme obese individuals entering a UK
      specialist weight management service prior to treatment commencement. METHODS:
      The sample comprised 263 extreme obese individuals who were referred to the
      service as a result of having a body mass index (BMI) >=40 kg/m2 or >=35 kg/m2
      with a co-morbid health condition. In a retrospective analysis, routinely
      collected baseline clinical examination data and self-report questionnaires
      (Impact of Weight on Quality of Life: IWQOL-Lite, EQ5D-3L, and Hospital Anxiety
      and Depression Scale: HADS) were analysed to examine the cross-sectional
      association between adiposity and quality of life. RESULTS: The sample was
      predominantly female (74.8%) with mean BMI 47.0+/-7.9 kg/m2. Increasing adiposity
      was significantly negatively associated with quality of life, with an increase of
      1 BMI unit associated with decreases of 1.93 in physical function (95% CI -2.86 -
      -1.00, p<0.001), 1.62 in self-esteem (95% CI -2.67 - -0.57, p<0.05), 2.69 in
      public distress (95% CI -3.75 - -1.62, p<0.001), 1.33 in work (95% CI -2.63 - 
      0.02, p<0.05), and 1.79 in total IWQOL-Lite scores (95% CI -2.65 - -0.93,
      p<0.001). Adiposity was associated with significantly increased risk of problems
      in mobility (OR = 3.44, 95% CI 1.47-8.05), and performing usual activities (OR =
      2.45, 95% CI 1.10-5.46) in highest relative to lowest BMI tertile. The prevalence
      of experience of symptoms of anxiety (70.3%) and depression (66.2%) as measured
      by HADS was consistently high. CONCLUSIONS: We identified a high prevalence of
      psychological co-morbidity, including widespread experience of symptoms of
      anxiety and depressive disorders and reduced quality of life among these extreme
      obese individuals seeking weight management treatment. Clinical implications
      include the need for the incorporation of strategies to improve mental well-being
      into multi-disciplinary weight management interventions.

PMID- 24671196
TI  - Global repression of host-associated genes of the Lyme disease spirochete through
      post-transcriptional modulation of the alternative sigma factor RpoS.
AB  - Borrelia burgdorferi, the agent of Lyme disease, is a vector-borne pathogen that
      transits between Ixodes ticks and vertebrate hosts. During the natural infectious
      cycle, spirochetes must globally adjust their transcriptome to survive in these
      dissimilar environments. One way B. burgdorferi accomplishes this is through the
      use of alternative sigma factors to direct transcription of specific genes. RpoS,
      one of only three sigma factors in B. burgdorferi, controls expression of genes
      required during tick-transmission and infection of the mammalian host. How
      spirochetes switch between different sigma factors during the infectious cycle
      has remained elusive. Here we establish a role for a novel protein, BBD18, in the
      regulation of the virulence-associated sigma factor RpoS. Constitutive expression
      of BBD18 repressed transcription of RpoS-dependent genes to levels equivalent to
      those observed in an rpoS mutant. Consistent with the global loss of RpoS
      dependent transcripts, we were unable to detect RpoS protein. However,
      constitutive expression of BBD18 did not diminish the amount of rpoS transcript,
      indicating post-transcriptional regulation of RpoS by BBD18. Interestingly, BBD18
      mediated repression of RpoS is independent of both the rpoS promoter and the 5'
      untranslated region, suggesting a mechanism of protein destabilization rather
      than translational control. We propose that BBD18 is a novel regulator of RpoS
      and its activity likely represents a first step in the transition from an RpoS-ON
      to an RpoS-OFF state, when spirochetes transition from the host to the tick
      vector. 

PMID- 24671202
TI  - Distinct pathways of ERK1/2 activation by hydroxy-carboxylic acid receptor-1.
AB  - Mechanistic investigations have shown that, upon agonist activation, hydroxy
      carboxylic acid receptor-1(HCA1) couples to a Gi protein and inhibits adenylate
      cyclase activity, leading to inhibition of liberation of free fatty acid.
      However, the underlying molecular mechanisms for HCA1 signaling remain largely
      unknown. Using CHO-K1 cells stably expressing HCA1, and L6 cells, which
      endogenously express rat HCA1 receptors, we found that activation of ERK1/2 by
      HCA1 was rapid, peaking at 5 min, and was significantly blocked by pertussis
      toxin. Furthermore, time course experiments with different kinase inhibitors
      demonstrated that HCA1 induced ERK1/2 activation via the extracellular Ca2+, PKC
      and IGF-I receptor transactivation-dependent pathways. In addition, we observed
      that pretreated the cells with M119K, an inhibitor of Gbetagamma subunit
      dependent signaling, effectively attenuated the ERK1/2 activation triggered by
      HCA1, suggesting a critical role for betagamma-subunits in HCA1-activated ERK1/2
      phosphorylation. Furthermore, the present results also indicated that the
      arrestin2/3 were not required for ERK1/2 activation. In conclusion, our findings
      demonstrate that upon binding to agonist, HCA1 receptors initially activate Gi,
      leading to dissociation of the Gbetagamma subunit from activated Gi, and
      subsequently induce ERK1/2 activation via two distinct pathways: one PKC
      dependent pathway and the other IGF-IR transactivation-dependent pathway. Our
      results provide the first in-depth evidence that defines the molecular mechanism
      of HCA1-mediated ERK1/2 activation. 

PMID- 24671203
TI  - Regulation of SIV antigen-specific CD4+ T cellular immunity via autophagosome
      mediated MHC II molecule-targeting antigen presentation in mice.
AB  - CD4+ T cell-mediated immunity has increasingly received attention due to its
      contribution in the control of HIV viral replication; therefore, it is of great
      significance to improve CD4+ T cell responses to enhance the efficacy of HIV
      vaccines. Recent studies have suggested that macroautophagy plays a crucial role
      in modulating adaptive immune responses toward CD4+ T cells or CD8+ T cells. In
      the present study, a new strategy based on a macroautophagy degradation mechanism
      is investigated to enhance CD4+ T cell responses against the HIV/SIV gag antigen.
      Our results showed that when fused to the autophagosome-associated LC3b protein,
      SIVgag protein can be functionally targeted to autophagosomes, processed by
      autophagy-mediated degradation in autolysosomes/lysosomes, presented to MHC II
      compartments and elicit effective potential CD4 T cell responses in vitro.
      Importantly, compared with the SIVgag protein alone, SIVgag-LC3b fusion antigen
      can induce a stronger antigen-specific CD4+ T cell response in mice, which is
      characterized by an enhanced magnitude and polyfunctionality. This study provides
      insight for the immunological modulation between viral and mammalian cells via
      autophagy, and it also presents an alternative strategy for the design of new
      antigens in the development of effective HIV vaccines. 

PMID- 24671204
TI  - How good is crude MDL for solving the bias-variance dilemma? An empirical
      investigation based on Bayesian networks.
AB  - The bias-variance dilemma is a well-known and important problem in Machine
      Learning. It basically relates the generalization capability (goodness of fit) of
      a learning method to its corresponding complexity. When we have enough data at
      hand, it is possible to use these data in such a way so as to minimize
      overfitting (the risk of selecting a complex model that generalizes poorly).
      Unfortunately, there are many situations where we simply do not have this
      required amount of data. Thus, we need to find methods capable of efficiently
      exploiting the available data while avoiding overfitting. Different metrics have
      been proposed to achieve this goal: the Minimum Description Length principle
      (MDL), Akaike's Information Criterion (AIC) and Bayesian Information Criterion
      (BIC), among others. In this paper, we focus on crude MDL and empirically
      evaluate its performance in selecting models with a good balance between goodness
      of fit and complexity: the so-called bias-variance dilemma, decomposition or
      tradeoff. Although the graphical interaction between these dimensions (bias and
      variance) is ubiquitous in the Machine Learning literature, few works present
      experimental evidence to recover such interaction. In our experiments, we argue
      that the resulting graphs allow us to gain insights that are difficult to unveil
      otherwise: that crude MDL naturally selects balanced models in terms of bias
      variance, which not necessarily need be the gold-standard ones. We carry out
      these experiments using a specific model: a Bayesian network. In spite of these
      motivating results, we also should not overlook three other components that may
      significantly affect the final model selection: the search procedure, the noise
      rate and the sample size. 

PMID- 24671205
TI  - V-ATPase proton pumping activity is required for adult zebrafish appendage
      regeneration.
AB  - The activity of ion channels and transporters generates ion-specific fluxes that
      encode electrical and/or chemical signals with biological significance. Even
      though it is long known that some of those signals are crucial for regeneration,
      only in recent years the corresponding molecular sources started to be identified
      using mainly invertebrate or larval vertebrate models. We used adult zebrafish
      caudal fin as a model to investigate which and how ion transporters affect
      regeneration in an adult vertebrate model. Through the combined use of
      biophysical and molecular approaches, we show that V-ATPase activity contributes
      to a regeneration-specific H+ ef'flux. The onset and intensity of both V-ATPase
      expression and H+ efflux correlate with the different regeneration rate along the
      proximal-distal axis. Moreover, we show that V-ATPase inhibition impairs
      regeneration in adult vertebrate. Notably, the activity of this H+ pump is
      necessary for aldh1a2 and mkp3 expression, blastema cell proliferation and fin
      innervation. To the best of our knowledge, this is the first report on the role
      of V-ATPase during adult vertebrate regeneration. 

PMID- 24671207
TI  - The bamboo-eating giant panda (Ailuropoda melanoleuca) has a sweet tooth:
      behavioral and molecular responses to compounds that taste sweet to humans.
AB  - A growing body of behavioral and genetic information indicates that taste
      perception and food sources are highly coordinated across many animal species.
      For example, sweet taste perception is thought to serve to detect and motivate
      consumption of simple sugars in plants that provide calories. Supporting this is
      the observation that most plant-eating mammals examined exhibit functional sweet
      perception, whereas many obligate carnivores have independently lost function of
      their sweet taste receptors and exhibit no avidity for simple sugars that humans
      describe as tasting sweet. As part of a larger effort to compare taste
      structure/function among species, we examined both the behavioral and the
      molecular nature of sweet taste in a plant-eating animal that does not consume
      plants with abundant simple sugars, the giant panda (Ailuropoda melanoleuca). We
      evaluated two competing hypotheses: as plant-eating mammals, they should have a
      well-developed sweet taste system; however, as animals that do not normally
      consume plants with simple sugars, they may have lost sweet taste function, as
      has occurred in strict carnivores. In behavioral tests, giant pandas avidly
      consumed most natural sugars and some but not all artificial sweeteners. Cell
      based assays revealed similar patterns of sweet receptor responses toward many of
      the sweeteners. Using mixed pairs of human and giant panda sweet taste receptor
      units (hT1R2+gpT1R3 and gpT1R2+hT1R3) we identified regions of the sweet receptor
      that may account for behavioral differences in giant pandas versus humans toward
      various sugars and artificial sweeteners. Thus, despite the fact that the giant
      panda's main food, bamboo, is very low in simple sugars, the species has a marked
      preference for several compounds that taste sweet to humans. We consider possible
      explanations for retained sweet perception in this species, including the
      potential extra-oral functions of sweet taste receptors that may be required for
      animals that consume plants. 

PMID- 24671210
TI  - The role of social media in recruiting for clinical trials in pregnancy.
AB  - BACKGROUND: Recruitment of women in the periconceptional period to clinical
      studies using traditional advertising through medical establishments is difficult
      and slow. Given the widespread use of the internet as a source for medical
      information and research, we analyze the impact of social media in the second
      phase of an ongoing randomized, open-label clinical trial among pregnant women.
      This study aims to assess the effectiveness of social media as a recruitment tool
      through the comparison of diverse recruitment techniques in two different phases
      of the trial. METHODS: Recruitment in Phase 1 of the study consisted solely of
      traditional healthcare-based sources. This was compared to Phase 2 of the study
      where traditional recruitment was continued and expanded, while social media was
      used as a supplementary source. Yearly recruitment and recruitment rates in the
      two phases were compared using the Mann Whitney U test. The contributions of each
      recruitment source to overall recruitment were analyzed, and the impact of
      potential confounders on recruitment rate was evaluated using a multiple
      regression and Interrupted Time Series Analysis. RESULTS: In the first phase of
      the study, with over 56 months of recruitment using traditional sources, 35 women
      were enrolled in the study, resulting in a mean rate of +/-0.62 recruits/month.
      In the 6 months implementing recruitment through social media, 45 women were
      recruited, for a 12-fold higher rate of +/-7.5 recruits/month. Attrition rates
      remained constant, suggesting that social media had a positive impact on
      recruitment. The Interrupted Time Series Analysis detected a significant
      difference in recruitment after the intervention of social media (p<0.0001) with
      an evident increase in the number of recruits observed after the use of social
      media. CONCLUSIONS: Clinicians and scientists recruiting for clinical studies
      should learn how to use online social media platforms to improve recruitment
      rates, thus increasing recruitment efficiency and cost-effectiveness.

PMID- 24671208
TI  - Combining EEG and MEG for the reconstruction of epileptic activity using a
      calibrated realistic volume conductor model.
AB  - To increase the reliability for the non-invasive determination of the irritative
      zone in presurgical epilepsy diagnosis, we introduce here a new experimental and
      methodological source analysis pipeline that combines the complementary
      information in EEG and MEG, and apply it to data from a patient, suffering from
      refractory focal epilepsy. Skull conductivity parameters in a six compartment
      finite element head model with brain anisotropy, constructed from individual MRI
      data, are estimated in a calibration procedure using somatosensory evoked
      potential (SEP) and field (SEF) data. These data are measured in a single run
      before acquisition of further runs of spontaneous epileptic activity. Our results
      show that even for single interictal spikes, volume conduction effects dominate
      over noise and need to be taken into account for accurate source analysis. While
      cerebrospinal fluid and brain anisotropy influence both modalities, only EEG is
      sensitive to skull conductivity and conductivity calibration significantly
      reduces the difference in especially depth localization of both modalities,
      emphasizing its importance for combining EEG and MEG source analysis. On the
      other hand, localization differences which are due to the distinct sensitivity
      profiles of EEG and MEG persist. In case of a moderate error in skull
      conductivity, combined source analysis results can still profit from the
      different sensitivity profiles of EEG and MEG to accurately determine location,
      orientation and strength of the underlying sources. On the other side,
      significant errors in skull modeling are reflected in EEG reconstruction errors
      and could reduce the goodness of fit to combined datasets. For combined EEG and
      MEG source analysis, we therefore recommend calibrating skull conductivity using
      additionally acquired SEP/SEF data. 

PMID- 24671209
TI  - Redistribution of flexibility in stabilizing antibody fragment mutants follows Le
      Chatelier's principle.
AB  - Le Chatelier's principle is the cornerstone of our understanding of chemical
      equilibria. When a system at equilibrium undergoes a change in concentration or
      thermodynamic state (i.e., temperature, pressure, etc.), La Chatelier's principle
      states that an equilibrium shift will occur to offset the perturbation and a new
      equilibrium is established. We demonstrate that the effects of stabilizing
      mutations on the rigidity <=> flexibility equilibrium within the native state
      ensemble manifest themselves through enthalpy-entropy compensation as the protein
      structure adjusts to restore the global balance between the two. Specifically, we
      characterize the effects of mutation to single chain fragments of the anti
      lymphotoxin-beta receptor antibody using a computational Distance Constraint
      Model. Statistically significant changes in the distribution of both rigidity and
      flexibility within the molecular structure is typically observed, where the local
      perturbations often lead to distal shifts in flexibility and rigidity profiles.
      Nevertheless, the net gain or loss in flexibility of individual mutants can be
      skewed. Despite all mutants being exclusively stabilizing in this dataset,
      increased flexibility is slightly more common than increased rigidity.
      Mechanistically the redistribution of flexibility is largely controlled by
      changes in the H-bond network. For example, a stabilizing mutation can induce an
      increase in rigidity locally due to the formation of new H-bonds, and
      simultaneously break H-bonds elsewhere leading to increased flexibility distant
      from the mutation site via Le Chatelier. Increased flexibility within the VH
      beta4/beta5 loop is a noteworthy illustration of this long-range effect. 

PMID- 24671211
TI  - Reproductive tract tumours: the scourge of woman reproduction ails Indian
      rhinoceroses.
AB  - In Indian rhinoceros, extensive leiomyoma, a benign smooth muscle tumour, was
      sporadically diagnosed post mortem and commonly thought of as contributing factor
      for reduced fecundity of this species in captivity. However, to date, the
      prevalence of reproductive tract tumours and their relevance for fecundity are
      unknown. Our analysis of the international studbook now reveals that females
      cease reproducing at the age of 18.1+/-1.2 years; equivalent to a reproductive
      lifespan of just 9.5+/-1.3 years. This short reproductive life is in sharp
      contrast to their longevity in captivity of over 40 years. Here we show, after
      examining 42% of the captive female population, that age-related genital tract
      tumours are highly prevalent in this endangered species. Growth and development
      of these tumours was found to be age-related, starting from the age of 10 years.
      All females older than 12 years had developed genital tumours, just 7-9 years
      past maturity. Tumour sizes ranged from 1.5-10 cm. With age, tumours became more
      numerous, sometimes merging into one large diffuse tumour mass. These tumours,
      primarily vaginal and cervical, presumably cause widespread young-age infertility
      by the age of 18 years. In few cases, tumour necrosis suggested possible
      malignancy of tumours. Possible consequences of such genital tract tumour
      infestation are hindered intromission, pain during mating, hampered sperm
      passage, risk of ascending infection during pregnancy, dystocia, or chronic
      vaginal bleeding. In humans, leiomyoma affect up to 80% of pre-menopause women.
      While a leading cause for infertility, pregnancy is known to reduce the risk of
      tumour development. However, different from human, surgical intervention is not a
      viable treatment option in rhinoceroses. Thus, in analogy to humans, we suggest
      early onset and seamless consecutive pregnancies to help reduce prevalence of
      this disease, better maintain a self-sustained captive population and improve
      animal welfare. 

PMID- 24671212
TI  - Creatinine index as a surrogate of lean body mass derived from urea Kt/V, pre
      dialysis serum levels and anthropometric characteristics of haemodialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Protein-energy wasting is common in long-term
      haemodialysis (HD) patients with chronic kidney disease and is associated with
      increased morbidity and mortality. The creatinine index (CI) is a simple and
      useful nutritional parameter reflecting the dietary skeletal muscle protein
      intake and skeletal muscle mass of the patient. Because of the complexity of
      creatinine kinetic modeling (CKM) to derive CI, we developed a more simplified
      formula to estimate CI in HD patients. DESIGN, SETTING, PARTICIPANTS &
      MEASUREMENTS: A large database of 549 HD patients followed over more than 20
      years including monthly CKM-derived CI values was used to develop a simple
      equation based on patient demographics, predialysis serum creatinine values and
      dialysis dose (spKt/V) using mixed regression models. RESULTS: The equation to
      estimate CI was developed based on age, gender, pre-dialysis serum creatinine
      concentrations and spKt/V urea. The equation-derived CI correlated strongly with
      the measured CI using CKM (correlation coefficient  = 0.79, p-value <0.001). The
      mean error of CI prediction using the equation was 13.47%. Preliminary examples
      of few typical HD patients have been used to illustrate the clinical relevance
      and potential usefulness of CI. CONCLUSIONS: The elementary equation used to
      derive CI using demographic parameters, pre-dialysis serum creatinine
      concentrations and dialysis dose is a simple and accurate surrogate measure for
      muscle mass estimation. However, the predictive value of the simplified CI
      assessment method on mortality deserves further evaluation in large cohorts of HD
      patients.

PMID- 24671213
TI  - Ecosystem-wide morphological structure of leaf-litter ant communities along a
      tropical latitudinal gradient.
AB  - General principles that shape community structure can be described based on a
      functional trait approach grounded on predictive models; increased attention has
      been paid to factors accounting for the functional diversity of species
      assemblages and its association with species richness along environmental
      gradients. We analyze here the interaction between leaf-litter ant species
      richness, the local communities' morphological structure and fundamental niche
      within the context of a northeast-southeast latitudinal gradient in one of the
      world's most species-rich ecosystems, the Atlantic Forest, representing 2,700 km
      of tropical rainforest along almost 20 degrees  of latitude in eastern Brazil.
      Our results are consistent with an ecosystem-wide pattern in communities'
      structure, with relatively high species turnover but functionally analogous leaf
      litter ant communities' organization. Our results suggest directional shifts in
      the morphological space along the environmental gradient from overdispersed to
      aggregated (from North to South), suggesting that primary productivity and
      environmental heterogeneity (altitude, temperature and precipitation in the case)
      determine the distribution of traits and regulate the assembly rules, shaping
      local leaf-litter ant communities. Contrary to the expected and most common
      pattern along latitudinal gradients, the Atlantic Forest leaf litter ant
      communities show an inverse pattern in richness, that is, richer communities in
      higher than in lower latitudes. The morphological specialization of communities
      showed more morphologically distinct communities at low latitudes and species
      redundancy at high latitudes. We claim that an inverse latitudinal gradient in
      primary productivity and environmental heterogeneity across the Atlantic forest
      may affect morphological diversity and species richness, enhancing species
      coexistence mechanisms, and producing thus the observed patterns. We suggest that
      a functional framework based on flexible enough traits should be pursued to allow
      comparisons at local, regional and global levels.

PMID- 24671214
TI  - Synthesis and properties of long [n]cumulenes (n >= 5).
AB  - Molecules composed of a contiguous sequence of double bonds, the [n]cumulenes,
      share structural similarities to both of their conjugated relatives, the polyenes
      and polyynes. The synthesis and properties of [n]cumulenes are, however, quite
      different from those of either polyenes or polyynes. At an infinite length,
      [n]cumulenes would provide one structural form of the hypothetical sp-hybridized
      carbon allotrope carbyne, while shorter derivatives offer model compounds to help
      to predict the properties of carbyne. Finally, derivatization of the pi-electron
      framework of [n]cumulenes provides a number of different synthetic
      transformations, with cycloaddition reactions being the most common. In this
      review, both historical and recent synthetic achievements toward long
      [n]cumulenes (n >= 5) are discussed. This is followed by a description of our
      current understanding of the physical and electronic structure of [n]cumulenes
      based on UV/vis spectroscopy and X-ray crystallography. Finally, the reactivity
      of long [n]cumulenes is described.

PMID- 24671215
TI  - Molecular topology as novel strategy for discovery of drugs with abeta lowering
      and anti-aggregation dual activities for Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: In this study, we demonstrate the use of Molecular
      topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and
      expands upon the principles governing the molecular connectivity theory of
      numerically characterizing molecular structures, in the present case, active anti
      AD drugs/agents, using topological descriptors to build models. Topological
      characterization has been shown to embody sufficient molecular information to
      provide strong correlation to therapeutic efficacy. EXPERIMENTAL APPROACH: We
      used MT to include multiple bioactive properties that allows for the
      identification of multi-functional single agent compounds, in this case, the dual
      functions of beta-amyloid (Abeta) -lowering and anti-oligomerization. Using this
      technology, we identified and designed novel compounds in chemical classes
      unrelated to current anti-AD agents that exert dual Abeta lowering and anti-Abeta
      oligomerization activities in animal models of AD. AD is a multifaceted disease
      with different pathological features. CONCLUSION AND IMPLICATIONS: Our study, for
      the first time, demonstrated that MT can provide novel strategy for discovering
      drugs with Abeta lowering and anti-aggregation dual activities for AD.

PMID- 24671217
TI  - Palladium-catalyzed air-based oxidative coupling of arylboronic acids with H
      phosphine oxides leading to aryl phosphine oxides.
AB  - We present a novel and highly efficient methodology that allows for the
      construction of C-P bonds via the palladium-catalyzed air-based oxidative
      coupling of various commercially available arylboronic acids with easily oxidized
      H-phosphine oxides leading to valuable aryl phosphine oxides, particularly
      triarylphosphine oxides, with the use of air as the green oxidant, broad
      substrate applicability and good to excellent yields. The described catalytic
      system should be an efficient complement to the Chan-Lam type reaction and be
      useful in synthetic programs. 

PMID- 24671216
TI  - Comparison of vegetarian diets and omnivorous diets on plasma level of HDL-c: a
      meta-analysis.
AB  - Low plasma level of high density lipoprotein cholesterol (HDL-c) was an
      independent risk factor for cardio vascular disorder, and associated with poor
      outcomes in pulmonary arterial hypertension. To compare the effects of vegetarian
      diets and omnivorous diets on HDL-c in plasma, we identified cross-sectional and
      cohort studies related to HDL-c listed on PubMed and ISI Web of Knowledge as well
      as the corresponding references (until Nov, 2013). Twelve studies with a total of
      4177 individuals were selected for meta-analysis. This meta-analysis indicates
      that vegetarian diets did not alter plasma HDL-c concentrations, as it wasn't
      initially expected by the authors [Standardized Mean Difference (SMD) = 0.02
      mmol/l; 95% confidence interval (CI): -0.19 to 0.22 mmol/l]. In Asia and Latin
      America countries, no significant differences in HDL-c levels between vegetarians
      and omnivores were found (SMD = -0.09 mmol/l; 95% CI: -0.43 to 0.25 mmol/l). In
      Europe and North America countries, the plasma level of HDL-c was also not
      different between the two diets (SMD = 0.09 mmol/l; 95% CI: -0.19 to 0.36
      mmol/l). In light of this meta-analysis, we conclude that there is no evidence
      that plasma HDL-c levels differs in vegetarians and omnivores, even after
      adjusting for cultural circumstances. 

PMID- 24671219
TI  - Anti-hyperglycemic and anti-oxidative activities of ginseng polysaccharides in
      STZ-induced diabetic mice.
AB  - Neutral (WGPN) and acidic (WGPA) polysaccharides were fractionated from ginseng
      polysaccharide. WGPN and WGPA decreased fasting blood glucose by different
      manners of administration. Intra-gastric administration of WGPA showed a marked
      hypoglycemic effect, which may be related to its anti-oxidative activity. The
      results indicated that WGPA may have anti-diabetic potential. 

PMID- 24671218
TI  - AmericaPlex26: a SNaPshot multiplex system for genotyping the main human
      mitochondrial founder lineages of the Americas.
AB  - Phylogeographic studies have described a reduced genetic diversity in Native
      American populations, indicative of one or more bottleneck events during the
      peopling and prehistory of the Americas. Classical sequencing approaches
      targeting the mitochondrial diversity have reported the presence of five major
      haplogroups, namely A, B, C, D and X, whereas the advent of complete
      mitochondrial genome sequencing has recently refined the number of founder
      lineages within the given diversity to 15 sub-haplogroups. We developed and
      optimized a SNaPshot assay to study the mitochondrial diversity in pre-Columbian
      Native American populations by simultaneous typing of 26 single nucleotide
      polymorphisms (SNPs) characterising Native American sub-haplogroups. Our assay
      proved to be highly sensitive with respect to starting concentrations of target
      DNA and could be applied successfully to a range of ancient human skeletal
      material from South America from various time periods. The AmericaPlex26 is a
      powerful assay with enhanced phylogenetic resolution that allows time- and cost
      efficient mitochondrial DNA sub-typing from valuable ancient specimens. It can be
      applied in addition or alternative to standard sequencing of the D-loop region in
      forensics, ancestry testing, and population studies, or where full-resolution
      mitochondrial genome sequencing is not feasible. 

PMID- 24671220
TI  - Fluorescence lifetime imaging of physiological free Cu(II) levels in live cells
      with a Cu(II)-selective carbonic anhydrase-based biosensor.
AB  - Copper is a required trace element that plays key roles in a number of human
      enzymes, such that copper deficiency or genetic defects in copper transport lead
      to serious or fatal disease. Rae, et al., had famously predicted that free copper
      ion levels in the cell cytoplasm were extremely low, typically too low to be
      observable. We recently developed a variant of human apocarbonic anhydrase II for
      sensing metal ions that exhibits 25-fold better selectivity for Cu(II) over
      Zn(II) than the wild type protein, enabling us to accurately measure Cu(II) in
      the presence of ordinary cellular (picomolar) concentrations of free zinc. We
      inserted a fluorescent labeled Cu(II)-specific variant of human apocarbonic
      anhydrase into PC-12 cells and found that the levels are indeed extremely low (in
      the femtomolar range). We imaged the free Cu(II) levels in living cells by means
      of frequency-domain fluorescence lifetime microscopy. Implications of this
      finding are discussed.

PMID- 24671221
TI  - Fox squirrels match food assessment and cache effort to value and scarcity.
AB  - Scatter hoarders must allocate time to assess items for caching, and to carry and
      bury each cache. Such decisions should be driven by economic variables, such as
      the value of the individual food items, the scarcity of these items, competition
      for food items and risk of pilferage by conspecifics. The fox squirrel, an
      obligate scatter-hoarder, assesses cacheable food items using two overt
      movements, head flicks and paw manipulations. These behaviors allow an
      examination of squirrel decision processes when storing food for winter survival.
      We measured wild squirrels' time allocations and frequencies of assessment and
      investment behaviors during periods of food scarcity (summer) and abundance
      (fall), giving the squirrels a series of 15 items (alternating five hazelnuts and
      five peanuts). Assessment and investment per cache increased when resource value
      was higher (hazelnuts) or resources were scarcer (summer), but decreased as
      scarcity declined (end of sessions). This is the first study to show that
      assessment behaviors change in response to factors that indicate daily and
      seasonal resource abundance, and that these factors may interact in complex ways
      to affect food storing decisions. Food-storing tree squirrels may be a useful and
      important model species to understand the complex economic decisions made under
      natural conditions. 

PMID- 24671222
TI  - Structural diversity and spectral and thermal properties of the first alkaline
      earth metal tetracyanidoborates: [Mg(H2O)6][B(CN)4]2, [Mg(H2O)2][B(CN)4]2,
      [Mg(DMF)6][B(CN)4]2, [Ca(H2O)3][B(CN)4]2, and [Ca(H2O)2(CH3CN)][B(CN)4]2.
AB  - The first members of tetracyanidoborate salts with alkaline earth cations,
      [Mg(H2O)6][B(CN)4]2 (1), [Mg(H2O)2][B(CN)4]2 (2), [Mg(DMF)6][B(CN)4]2 (3),
      [Ca(H2O)3][B(CN)4]2 (4), and [Ca(H2O)2(CH3CN)][B(CN)4]2 (5), were synthesized.
      Their structures, obtained by single crystal X-ray diffraction, IR- and Raman
      spectra, as well as their thermal properties were determined. Whereas 1 and 3
      consist of isolated ions, the other three compounds comprise coordination
      polymers. IR and Raman spectra give information about the coordination modes of
      the respective tetracyanidoborate anions. Calorimetric measurements show that the
      coordinated solvent molecules can be removed at elevated temperatures and
      anhydrous/solvent free compounds form. The anhydrous compounds are thermally very
      stable. They do not start to decompose below 500  degrees C. No melting is
      observed below decomposition. 

PMID- 24671223
TI  - Phototaxis and polarotaxis hand in hand: night dispersal flight of aquatic
      insects distracted synergistically by light intensity and reflection
      polarization.
AB  - Based on an earlier observation in the field, we hypothesized that light
      intensity and horizontally polarized reflected light may strongly influence the
      flight behaviour of night-active aquatic insects. We assumed that phototaxis and
      polarotaxis together have a more harmful effect on the dispersal flight of these
      insects than they would have separately. We tested this hypothesis in a multiple
      choice field experiment using horizontal test surfaces laid on the ground. We
      offered simultaneously the following visual stimuli for aerial aquatic insects:
      (1) lamplit matte black canvas inducing phototaxis alone, (2) unlit shiny black
      plastic sheet eliciting polarotaxis alone, (3) lamplit shiny black plastic sheet
      inducing simultaneously phototaxis and polarotaxis, and (4) unlit matte black
      canvas as a visually unattractive control. The unlit matte black canvas trapped
      only a negligible number (13) of water insects. The sum (16,432) of the total
      numbers of water beetles and bugs captured on the lamplit matte black canvas
      (7,922) and the unlit shiny black plastic sheet (8,510) was much smaller than the
      total catch (29,682) caught on the lamplit shiny black plastic sheet. This
      provides experimental evidence for the synergistic interaction of phototaxis
      (elicited by the unpolarized direct lamplight) and polarotaxis (induced by the
      strongly and horizontally polarized plastic-reflected light) in the investigated
      aquatic insects. Thus, horizontally polarizing artificial lamplit surfaces can
      function as an effective ecological trap due to this synergism of optical cues,
      especially in the urban environment.

PMID- 24671225
TI  - Primary malignant cardiac tumors.
AB  - PURPOSE: The literature on primary malignant cardiac tumors is relatively limited
      because of their rare incidence. This study aimed to provide a proposed treatment
      strategy for primary malignant cardiac tumors. METHODS: The follow-up outcomes of
      29 patients with primary malignant cardiac tumors operated, and 8 primary
      malignant cardiac tumors considered not operable from 1985 to 2013 in the First
      Affiliated Hospital of China Medical University were retrospectively analyzed.
      RESULTS: Of operation receivers, ten patients had positive surgical margins and
      nineteen patients had negative surgical margins. Eleven patients received a post
      operative neoadjuvant chemotherapy. Patients rejected to surgery had a lower
      survival compared with operation receivers (15 vs 23 months, P = 0.011). However,
      there were no significant differences in survival in patients rejected to surgery
      than in patients who had positive surgical margins (15 vs 16 months, P = 0.874).
      Patients who had positive surgical margins had a median overall survival duration
      of only 16 months, whereas patients with negative surgical margins had a median
      overall survival duration of 27 months (P = 0.002). There were no significant
      differences in survival in patients with receiving a post-operative adjuvant
      chemotherapy than in the rest of the population (20 vs 25 months, P = 0.150).
      CONCLUSIONS: The prognosis for patients with primary malignant cardiac tumors
      remains very poor. Each patient should be managed on an individual basis, and
      variety of treatment strategy should be performed. Maximizing the possibility of
      obtaining negative surgical margins may prolong survival.

PMID- 24671224
TI  - JAB1 and phospho-Ser10 p27 expression profile determine human hepatocellular
      carcinoma prognosis.
AB  - PURPOSE: To elucidate the clinicopathological significance and the role of Jun
      Activation Domain-Binding Protein 1 (JAB1), Ser10-phosphorylated p27 (p27S10),
      and total p27 in human hepatocellular carcinoma (HCC) prognosis. METHODS: We
      evaluated the expression of JAB1 and p27S10 in tissues by immunohistochemical and
      immunoblot analyses. p27 Ser10 phosphorylation and Ser10 phosphorylation
      dependent p27-JAB1 interaction were demonstrated in proliferating Huh7 cells
      following transfection of pEGFP-p27WT/p27S10A/p27S10D plasmids and pcDNA3.1
      p27WT/p27S10A/p27S10D-Myc plasmids. Univariate and multivariate analysis were
      used to determine their role in HCC prognosis. RESULTS: JAB1 and p27S10 are
      overexpressed in HCC samples compared with paired normal tissues. There was a
      strong correlation between JAB1 and p27S10 expression (P < 0.001), and expression
      of both inversely correlated with total p27 levels (P < 0.001). High JAB1 and
      p27S10 expression correlated with histological grade, vascular invasion, and
      serum alpha-fetoprotein (AFP) level (all P < 0.01). Total p27 expression also
      correlated with histological tumor grade (P = 0.048) and AFP level (P = 0.015).
      The p27S10(high)/JAB1(high)/p27(1ow) profile was the most reliable indication of
      poor prognostic. Ser10 phosphorylation increased and total p27 levels decreased
      in a time-dependent manner in serum-starved Huh7 cells following addition of
      serum. Immunoprecipitation analysis revealed that p27 Ser-to-Asp substitution at
      position 10 (S10D) markedly enhanced the interaction between JAB1 and p27, but
      replacement of S10A reduced binding. CONCLUSIONS: This study revealed that
      combined JAB1, p27S10, and total p27 expression may serve as a prognostic marker
      for HCC.

PMID- 24671226
TI  - Estrogen receptor beta2 is inversely correlated with Ki-67 in hyperplastic and
      noninvasive neoplastic breast lesions.
AB  - PURPOSE: The purpose of the study is to compare expression levels of
      EpsilonRalpha, ERbeta1, ERbeta2 and cell proliferation marker Ki-67 in normal
      breast and hyperplastic and noninvasive neoplastic breast lesions. MATERIALS AND
      METHODS: Routinely processed breast tissue from 55 patients provided 65 cases of
      noninvasive lesions, namely, epithelial hyperplasia of usual type (HUT), apocrine
      metaplasia (AM), atypical hyperplasia (AH) and ductal carcinoma in situ (DCIS)
      and 14 cases of adjacent normal breast tissue. Expression of ERalpha, ERbeta1 and
      ERbeta2 were evaluated using immunohistochemistry and correlated with Ki-67
      labeling index (Ki-67 LI) and menopausal status of the patients. RESULTS:
      Compared with normal breast, ERalpha expression increased in low to intermediate
      grade DCIS (DCIS1/2) and tended to decrease in high-grade DCIS, while ERbeta1
      expression decreased in DCIS irrespective of grade. Mean Ki-67 LI in HUT, low to
      intermediate-grade DCIS and high-grade DCIS was higher than in normal breast.
      Higher than normal Ki-67 LI correlated with low ERbeta2 expression in the whole
      set of cases and with high ERalpha expression and low ERbeta2 expression in the
      postmenopausal cases of the subset that is generated by excluding AM and high
      grade DCIS. Postmenopausal status correlated with low ERbeta1 expression in the
      whole set and with higher than normal Ki-67 LI, high ERalpha expression and low
      ERbeta1 expression in the subset. CONCLUSIONS: These findings are in accordance
      with an ERalpha-opposing oncosuppressive role of ERbeta2 in mammary
      carcinogenesis along the HUT-AH-DCIS1/2 pathway.

PMID- 24671227
TI  - Renal tumor size is an independent prognostic factor for overall survival in von
      Hippel-Lindau disease.
AB  - OBJECTIVES: To evaluate the effect of renal cell carcinoma (RCC) on survival in
      von Hippel-Lindau (VHL) disease and to assess the relationship between tumor size
      and survival. MATERIALS AND METHODS: In this retrospective cohort study, the
      medical records of 72 patients who presented with VHL disease between 1994 and
      2012 were reviewed. Clinical VHL-related characteristics were analyzed, and the
      prognostic value of renal tumor size for overall survival was assessed by using
      Cox regression models. RESULTS: Of the 72 VHL patients, 42 (58.3 %) and 30 (41.7
      %) were male and female, respectively. The mean age was 37.9 years, and the
      median follow-up period was 61.5 months. In terms of VHL-related manifestations,
      40 (55.6 %) had RCC, 46 (63.8 %) had hemangioblastoma in the cerebellum, 10 (13.9
      %) had hemangioblastoma in the spinal cord, 34 (47.2 %) had a pancreatic mass, 18
      (25.0 %) had pheochromocytoma, and 14 (19.4 %) had retinal capillary hemangioma.
      RCC was a major cause of mortality: Of the 11 patients who died, nine (12.5 %)
      died due to RCC progression. The 5-year overall survival rate was 85.6 % for all
      patients, 96.9 % for patients without RCC, 83.6 % for patients with RCC < 3 cm,
      and 75.8 % for patients with RCC >= 3 cm. Multivariable analysis showed that RCC
      >= 3 cm was an independent predictor of overall survival (HR 9.87, 95 % CI 1.17
      83.00, p = 0.035) along with age (HR 1.05, 95 % CI 1.01-1.10, p = 0.027).
      CONCLUSIONS: Renal tumor size was an independent prognostic factor for overall
      survival in VHL disease. This observation will be helpful for planning RCC
      treatment in VHL disease.

PMID- 24671228
TI  - Meta-analysis of the effects of beta blocker on survival time in cancer patients.
AB  - PURPOSE: This study was to elucidate the potential benefit of beta blockers on
      cancer survival. METHODS: We comprehensively searched PubMed, Embase, and the
      Cochrane Library from their inception to April 2013. Two authors independently
      screened and reviewed the eligibility of each study and coded the participants,
      treatment, and outcome characteristics. The primary outcomes were overall
      survival (OS) and disease-free survival (DFS). RESULTS: Twelve studies published
      between 1993 and 2013 were included in the final analysis. Four papers reported
      results from 10 independent groups, resulting in a total of 18 comparisons based
      on data obtained from 20,898 subjects. Effect sizes (hazard ratios, HR) were
      heterogeneous, and random-effects models were used in the analyses. The meta
      analysis demonstrated that beta blocker use is associated with improved OS (HR
      0.79; 95 % CI 0.67-0.93; p = 0.004) and DFS (HR 0.69; 95 % CI 0.53-0.91; p =
      0.009). Although statistically not significant, the effect size was greater in
      patients with low-stage cancer or cancer treated primarily with surgery than in
      patients with high-stage cancer or cancer treated primarily without surgery (HR
      0.60 vs. 0.78, and 0.60 vs. 0.80, respectively). Although only two study codes
      were analyzed, the studies using nonselective beta blockers showed that there was
      no overall effect on OS (HR 0.52, 95 % CI 0.09-3.04). CONCLUSION: This meta
      analysis provides evidence that beta blocker use can be associated with the
      prolonged survival of cancer patients, especially patients with early-stage
      cancer treated primarily with surgery.

PMID- 24671229
TI  - Metal complexes designed to bind to amyloid-beta for the diagnosis and treatment
      of Alzheimer's disease.
AB  - Alzheimer's disease is the most common form of age-related neurodegenerative
      dementia. The disease is characterised by the presence of plaques in the cerebral
      cortex. The major constituent of these plaques is aggregated amyloid-beta
      peptide. This review focuses on the molecular aspects of metal complexes designed
      to bind to amyloid-beta. The development of radioactive metal-based complexes of
      copper and technetium designed as diagnostic imaging agents to detect amyloid
      burden in the brain is discussed. Separate sections of the review discuss the use
      of luminescent metal complexes to act as non-conventional probes of amyloid
      formation and recent research into the use of metal complexes as inhibitors of
      amyloid formation and toxicity. 

PMID- 24671230
TI  - Extended mechanistic aspects on photoinitiated polymerization of 1,6-hexanediol
      diacrylate by hexaarylbisimidazoles and heterocyclic mercapto compounds.
AB  - Chlorine substituted hexaarylbisimidazole (o-Cl-HABI) efficiently initiates
      radical polymerization of multifunctional acrylic esters in the presence of a
      heterocyclic mercapto compound if the latter can form its tautomeric thione.
      Exposure of o-Cl-HABI results in lophyl radicals, which efficiently add to the
      thione in the first step while the second step releases a highly reactive thiyl
      radical from this intermediate. LC-MS and CID-MS measurements support this
      reaction scheme. Furthermore, photo-DSC experiments applying UV light between 320
      and 380 nm showed that mercaptotriazole and phenylmercaptotriazole exhibited the
      best reactivity in the monomer 1,6-hexanediol diacrylate (HDDA) while alkyl
      substituted mercaptotriazoles showed less reactivity. Change of the triazole
      heterocycle by mercaptoimidazole resulted in a significant decrease of
      photoinitiation efficiency. This heterocycle does not form the corresponding
      thione in HDDA as shown by NMR measurements. Replacement of mercaptotriazole by
      an alkylthiol leads to a system showing the lowest photoinitiation efficiency in
      this series. Formation of thione structure in the case of heterocyclic mercapto
      compounds may cause higher reactivity of the heterocyclic mercapto compounds with
      the lophyl radical in the monomer chosen. 

PMID- 24671231
TI  - High-throughput quantitative proteomic analysis of dengue virus type 2 infected
      A549 cells.
AB  - Disease caused by dengue virus is a global health concern with up to 390 million
      individuals infected annually worldwide. There are no vaccines or antiviral
      compounds available to either prevent or treat dengue disease which may be fatal.
      To increase our understanding of the interaction of dengue virus with the host
      cell, we analyzed changes in the proteome of human A549 cells in response to
      dengue virus type 2 infection using stable isotope labelling in cell culture
      (SILAC) in combination with high-throughput mass spectrometry (MS). Mock and
      infected A549 cells were fractionated into nuclear and cytoplasmic extracts
      before analysis to identify proteins that redistribute between cellular
      compartments during infection and reduce the complexity of the analysis. We
      identified and quantified 3098 and 2115 proteins in the cytoplasmic and nuclear
      fractions respectively. Proteins that showed a significant alteration in amount
      during infection were examined using gene enrichment, pathway and network
      analysis tools. The analyses revealed that dengue virus infection modulated the
      amounts of proteins involved in the interferon and unfolded protein responses,
      lipid metabolism and the cell cycle. The SILAC-MS results were validated for a
      select number of proteins over a time course of infection by Western blotting and
      immunofluorescence microscopy. Our study demonstrates for the first time the
      power of SILAC-MS for identifying and quantifying novel changes in cellular
      protein amounts in response to dengue virus infection. 

PMID- 24671233
TI  - Can the National Disability Insurance Scheme work for mental health?

PMID- 24671232
TI  - Preterm birth and antidepressant medication use during pregnancy: a systematic
      review and meta-analysis.
AB  - INTRODUCTION: Preterm birth is a major contributor to neonatal morbidity and
      mortality and its rate has been increasing over the past two decades.
      Antidepressant medication use during pregnancy has also been rising, with rates
      up to 7.5% in the US. The objective was to systematically review the literature
      to determine the strength of the available evidence relating to a possible
      association between antidepressant use during pregnancy and preterm birth.
      METHODS: We conducted a computerized search in PUBMED, MEDLINE and PsycINFO
      through September 2012, supplemented with a manual search of reference lists, to
      identify original published research on preterm birth rates in women taking
      antidepressants during pregnancy. Data were independently extracted by two
      reviewers, and absolute and relative risks abstracted or calculated. Our a priori
      design was to group studies by level of confounding adjustment and by timing of
      antidepressant use during pregnancy; we used random-effects models to calculate
      summary measures of effect. RESULTS: Forty-one studies met inclusion criteria.
      Pooled adjusted odds ratios (95% CI) were 1.53 (1.40-1.66) for antidepressant use
      at any time and 1.96 (1.62-2.38) for 3rd trimester use. Controlling for a
      diagnosis of depression did not eliminate the effect. There was no increased risk
      [1.16 (0.92-1.45)] in studies that identified patients based on 1st trimester
      exposure. Sensitivity analyses demonstrated unmeasured confounding would have to
      be strong to account for the observed association. DISCUSSION: Published evidence
      is consistent with an increased risk of preterm birth in women taking
      antidepressants during the 2nd and 3rd trimesters, although the possibility of
      residual confounding cannot be completely ruled out.

PMID- 24671234
TI  - Drugs and psychosis ... and now for some good news.

PMID- 24671235
TI  - Value of real world economic evaluations of crisis accommodation programmes for
      patients with severe mental illness.

PMID- 24671236
TI  - Weak association of glyoxalase 1 (GLO1) variants with autism spectrum disorder.
AB  - The prevalence of the autism spectrum disorder (ASD) was recently estimated to 1
      in 88 children by the CDC MMWR. In up to 25 % of the cases, the genetic cause can
      be identified. Past studies identified increased level of advanced glycation end
      products (AGE) in the brain samples of ASD patients. The methylglyoxal (MG) is
      one of the main precursors for AGE formation. Humans developed effective
      mechanism of the MG metabolism involving two enzymes glyoxalase 1 (GLO1) and
      hydroxyacylglutathione hydrolase (HAGH). Our aim was to analyse genetic variants
      of GLO1 and HAGH in population of 143 paediatric participants with ASD. We
      detected 7 genetic variants in GLO1 and 16 variants in HAGH using high-resolution
      melting (HRM) analysis. A novel association between variant rs1049346 and ASD [OR
      (allele C)] = 1.5; 95 % CI = 1.1-2.2 and p < 0.05) was identified, and weak
      association between ASD and variant rs2736654 [OR (allele A)] = 2.2; 95 % CI =
      0.99-4.9; p = 0.045) was confirmed. Additionally, a novel genetic variant (GLO1
      c.484G > A, p.Ala161Thr) with predicted potentially damaging effect on the
      activity of the glyoxalase 1 that may contribute to the aetiology of ASD was
      identified in one participant with ASD. No association between genetic variants
      of the HAGH gene and ASD was found. Increased level of MG and, consequently, AGEs
      can induce oxidative stress, mitochondrial dysfunction and inflammation all of
      which have been implicated to act in the aetiology of the ASD. Our results
      indicate potential importance of MG metabolism in ASD. However, these results
      must be interpreted with caution until a causative relation is demonstrated.

PMID- 24671237
TI  - Prebiotic effect during the first year of life in healthy infants fed formula
      containing GOS as the only prebiotic: a multicentre, randomised, double-blind and
      placebo-controlled trial.
AB  - PURPOSE: Currently, there is no consensus concerning the possible beneficial
      colonic and systemic effects of prebiotic-containing infant formula. This study
      assesses whether the feeding of a galactooligosaccharides (GOS)-containing infant
      formula (0.44 g/dl of GOS) and the subsequent feeding of a GOS-containing follow
      on formula (0.50 g/dl of GOS) have a prebiotic effect on intestinal microbiota
      that helps to decrease infections and allergy manifestations in healthy infants
      during the first year of life. METHODS: A multicentre, randomised, double-blind
      and placebo-controlled trial was carried out on 365 healthy term infants enrolled
      before 8 weeks of age and randomly assigned to a formula with or without GOS,
      until 12 months of age. The incidence of infections and allergy manifestations,
      the antibiotics prescribed and faecal characteristics were recorded up to 12
      months of age, while faecal samples were collected up to 4 months for the
      measurement of secretory immunoglobulin A, short-chain fatty acids and
      microbiota. RESULTS: A prebiotic effect on the faecal analysis was observed at 4
      months of life. The GOS group showed a lower faecal pH (P = 0.019), a lower
      decreasing trend in secretory immunoglobulin A (P = 0.078), lower butyric acid
      concentration (P = 0.040) and an increase in Bifidobacterium counts (P = 0.010).
      Changes in faecal characteristics involved greater frequency (P < 0.001) and
      softer consistency (P < 0.05). The incidence of infections or allergic
      manifestations during the first year of life was similar in both groups, with no
      statistical differences (P > 0.05). CONCLUSIONS: The feeding of GOS-containing
      infant formula produced a definite prebiotic effect consisting of changes in
      faecal composition and microbiota, and in faecal consistency and the frequency of
      defaecation. No changes in the incidence of infection or allergic manifestation
      during the first year of life were observed.

PMID- 24671238
TI  - Crystal structure of ORF210 from E. coli O157:H1 phage CBA120 (TSP1), a putative
      tailspike protein.
AB  - Bacteriophage tailspike proteins act as primary receptors, often possessing
      endoglycosidase activity toward bacterial lipopolysaccharides or other
      exopolysaccharides, which enable phage absorption and subsequent DNA injection
      into the host. Phage CBA120, a contractile long-tailed Viunalikevirus phage
      infects the virulent Escherichia coli O157:H7. This phage encodes four putative
      tailspike proteins exhibiting little amino acid sequence identity, whose
      biological roles and substrate specificities are unknown. Here we focus on the
      first tailspike, TSP1, encoded by the orf210 gene. We have discovered that TSP1
      is resistant to protease degradation, exhibits high thermal stability, but does
      not cleave the O157 antigen. An immune-dot blot has shown that TSP1 binds
      strongly to non-O157:H7 E. coli cells and more weakly to K. pneumoniae cells, but
      exhibits little binding to E. coli O157:H7 strains. To facilitate structure
      function studies, we have determined the crystal structure of TSP1 to a
      resolution limit of 1.8 A. Similar to other tailspikes proteins, TSP1 assembles
      into elongated homotrimers. The receptor binding region of each subunit adopts a
      right-handed parallel beta helix, reminiscent yet not identical to several known
      tailspike structures. The structure of the N-terminal domain that binds to the
      virion particle has not been seen previously. Potential endoglycosidase catalytic
      sites at the three subunit interfaces contain two adjacent glutamic acids, unlike
      any catalytic machinery observed in other tailspikes. To identify potential sugar
      binding sites, the crystal structures of TSP1 in complexes with glucose, alpha
      maltose, or alpha-lactose were determined. These structures revealed that each
      sugar binds in a different location and none of the environments appears
      consistent with an endoglycosidase catalytic site. Such sites may serve to bind
      sugar units of a yet to be identified bacterial exopolysaccharide. 

PMID- 24671239
TI  - Correlation between glucose uptake and membrane potential in Leishmania parasites
      isolated from DCL patients with therapeutic failure: a proof of concept.
AB  - Besides infection with drug-resistant parasites, therapeutic failure in
      leishmaniasis may be caused by altered drug pharmacokinetics, re-infection, and
      host immunologic compromise. Our aim has been to evaluate if relapses that occur
      in patients suffering from diffuse cutaneous leishmaniasis (DCL) associate with
      changes in the fitness of infecting organisms. Therefore, in isolates from
      patients suffering DCL, we correlated glucose uptake and plasma membrane
      potential and compared the results with those obtained from reference strains.
      The data demonstrate that Leishmania parasites causing DCL incorporate glucose at
      an efficient rate, albeit without significant changes in the plasma membrane
      potential as their corresponding reference strains. The isolate that did not
      change its accumulation rate of glucose compared to its reference strain
      expressed a less polarized membrane potential that was insensitive to
      mitochondrial inhibitors, suggesting a metabolic dysfunction that may result in
      glycolysis being the main source of ATP. The results constitute a proof of
      concept that indicates that parasites causing DCL adapted well to drug pressure
      and expressed an increased fitness. That is, that in Leishmania mexicana and
      Leishmania amazonensis, parasites isolated from DCL patients, a strong
      modification of the parasite physiology might occur. As consequences, the
      parasites adapted well to drug pressure, increased their fitness, and they had an
      efficient glucose uptake rate albeit not significant changes in membrane
      potential as their corresponding reference strains. Further validation of the
      concepts herein established and whether or not the third isolate corresponds with
      a drug-resistant phenotype need to be demonstrated at the genetic level. 

PMID- 24671240
TI  - Coping with dehydration: sympathetic activation and regulation of glutamatergic
      transmission in the hypothalamic PVN.
AB  - Autonomic and endocrine profiles of chronic hypertension and heart failure
      resemble those of acute dehydration. Importantly, all of these conditions are
      associated with exaggerated sympathetic nerve activity (SNA) driven by
      glutamatergic activation of the hypothalamic paraventricular nucleus (PVN). Here,
      studies sought to gain insight into mechanisms of disease by determining the role
      of PVN ionotropic glutamate receptors in supporting SNA and mean arterial
      pressure (MAP) during dehydration and by elucidating mechanisms regulating
      receptor activity. Blockade of PVN N-methyl-D-aspartate (NMDA) receptors reduced
      (P < 0.01) renal SNA and MAP in urethane-chloralose-anesthetized dehydrated (DH)
      (48 h water deprivation) rats, but had no effect in euhydrated (EH) controls.
      Blockade of PVN alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors had no effect in either group. NMDA in PVN caused dose-dependent
      increases of renal SNA and MAP in both groups, but the maximum agonist evoked
      response (Emax) of the renal SNA response was greater (P < 0.05) in DH rats. The
      latter was not explained by increased PVN expression of NMDA receptor NR1 subunit
      protein, increased PVN neuronal excitability, or decreased brain water content.
      Interestingly, PVN injection of the pan-specific excitatory amino acid
      transporter (EAAT) inhibitor DL-threo-beta-benzyloxyaspartic acid produced
      smaller sympathoexcitatory and pressor responses in DH rats, which was associated
      with reduced glial expression of EAAT2 in PVN. Like chronic hypertension and
      heart failure, dehydration increases excitatory NMDA receptor tone in PVN.
      Reduced glial-mediated glutamate uptake was identified as a key contributing
      factor. Defective glutamate uptake in PVN could therefore be an important, but as
      yet unexplored, mechanism driving sympathetic hyperactivity in chronic
      cardiovascular diseases.

PMID- 24671241
TI  - Optical mapping of the electrical activity of isolated adult zebrafish hearts:
      acute effects of temperature.
AB  - The zebrafish (Danio rerio) has emerged as an important model for developmental
      cardiovascular (CV) biology; however, little is known about the cardiac function
      of the adult zebrafish enabling it to be used as a model of teleost CV biology.
      Here, we describe electrophysiological parameters, such as heart rate (HR),
      action potential duration (APD), and atrioventricular (AV) delay, in the
      zebrafish heart over a range of physiological temperatures (18-28 degrees C).
      Hearts were isolated and incubated in a potentiometric dye, RH-237, enabling
      electrical activity assessment in several distinct regions of the heart
      simultaneously. Integration of a rapid thermoelectric cooling system facilitated
      the investigation of acute changes in temperature on critical
      electrophysiological parameters in the zebrafish heart. While intrinsic HR varied
      considerably between fish, the ex vivo preparation exhibited impressively stable
      HRs and sinus rhythm for more than 5 h, with a mean HR of 158 +/- 9 bpm (means +/
      SE; n = 20) at 28 degrees C. Atrial and ventricular APDs at 50% repolarization
      (APD50) were 33 +/- 1 ms and 98 +/- 2 ms, respectively. Excitation originated in
      the atrium, and there was an AV delay of 61 +/- 3 ms prior to activation of the
      ventricle at 28 degrees C. APD and AV delay varied between hearts beating at
      unique HRs; however, APD and AV delay did not appear to be statistically
      dependent on intrinsic basal HR, likely due to the innate beat-to-beat
      variability within each heart. As hearts were cooled to 18 degrees C (by 1
      degrees C increments), HR decreased by ~40%, and atrial and ventricular APD50
      increased by a factor of ~3 and 2, respectively. The increase in APD with cooling
      was disproportionate at different levels of repolarization, indicating unique
      temperature sensitivities for ion currents at different phases of the action
      potential. The effect of temperature was more apparent at lower levels of
      repolarization and, as a whole, the atrial APD was the cardiac parameter most
      affected by acute temperature change. In conclusion, this study describes a
      preparation enabling the in-depth analysis of transmembrane potential dynamics in
      whole zebrafish hearts. Because the zebrafish offers some critical advantages
      over the murine model for cardiac electrophysiology, optical mapping studies
      utilizing zebrafish offer insightful information into the understanding and
      treatment of human cardiac arrhythmias, as well as serving as a model for other
      teleosts.

PMID- 24671242
TI  - Myosin heavy-chain isoforms in the flight and leg muscles of hummingbirds and
      zebra finches.
AB  - Myosin heavy chain (MHC) isoform complement is intimately related to a muscle's
      contractile properties, yet relatively little is known about avian MHC isoforms
      or how they may vary with fiber type and/or the contractile properties of a
      muscle. The rapid shortening of muscles necessary to power flight at the high
      wingbeat frequencies of ruby-throated hummingbirds and zebra finches (25-60 Hz),
      along with the varied morphology and use of the hummingbird hindlimb, provides a
      unique opportunity to understand how contractile and morphological properties of
      avian muscle may be reflected in MHC expression. Isoforms of the hummingbird and
      zebra finch flight and hindlimb muscles were electrophoretically separated and
      compared with those of other avian species representing different contractile
      properties and fiber types. The flight muscles of the study species operate at
      drastically different contraction rates and are composed of different
      histochemically defined fiber types, yet each exhibited the same, single MHC
      isoform corresponding to the chicken adult fast isoform. Thus, despite
      quantitative differences in the contractile demands of flight muscles across
      species, this isoform appears necessary for meeting the performance demands of
      avian powered flight. Variation in flight muscle contractile performance across
      species may be due to differences in the structural composition of this conserved
      isoform and/or variation within other mechanically linked proteins. The leg
      muscles were more varied in their MHC isoform composition across both muscles and
      species. The disparity in hindlimb MHC expression between hummingbirds and the
      other species highlights previously observed differences in fiber type
      composition and thrust production during take-off.

PMID- 24671244
TI  - An acute method to test leptin responsiveness in rats.
AB  - Continuous subcutaneous administration of leptin normalizes blood glucose levels
      in rodent models of Type 1 and Type 2 diabetes independent of changes in food
      intake, body weight, and plasma insulin. We tested whether an acute intravenous
      leptin infusion changed blood glucose in normal and diet-induced leptin-resistant
      rats to determine whether this measure could be used as a marker of leptin
      sensitivity. Leptin-responsive chow-fed rats and diet-induced leptin-resistant
      male Sprague-Dawley rats were fitted with thoracic jugular vein catheters. Four
      days after surgery, conscious rats were infused intravenously with either saline
      for 32 min, low-dose (LD) leptin (1.9 MUg.kg(-1).min(-1)) followed by high-dose
      (HD) leptin (3.8 MUg.kg(-1).min(-1)) for 16 min each, or only HD leptin for 16
      min. There was no change in blood glucose after an acute intravenous infusion of
      either LD leptin or HD leptin alone for 16 min. An intravenous infusion of LD
      followed by HD leptin for 16 min each significantly decreased serum glucose in
      leptin-responsive rats but not in leptin-resistant rats. Leptin infusions
      increased serum leptin in all rat groups but had no effect on plasma glucagon or
      12-h weight gain and energy intake in any group of rats. These results show that
      leptin has an acute glucose-lowering effect that reflects the leptin
      responsiveness of the rat. This effect is consistent across controls and
      different leptin-resistant rat models, and the acute nonlethal test provides a
      novel method of testing leptin responsiveness in rats.

PMID- 24671243
TI  - Chronic binge alcohol consumption alters myogenic gene expression and reduces in
      vitro myogenic differentiation potential of myoblasts from rhesus macaques.
AB  - Chronic alcohol abuse is associated with skeletal muscle myopathy. Previously, we
      demonstrated that chronic binge alcohol (CBA) consumption by rhesus macaques
      accentuates skeletal muscle wasting at end-stage of simian immunodeficiency virus
      (SIV) infection. A proinflammatory, prooxidative milieu and enhanced ubiquitin
      proteasome activity were identified as possible mechanisms leading to loss of
      skeletal muscle. The possibility that impaired regenerative capacity, as
      reflected by the ability of myoblasts derived from satellite cell (SCs) to
      differentiate into myotubes has not been examined. We hypothesized that the
      inflammation and oxidative stress in skeletal muscle from CBA animals impair the
      differentiation capacity of myoblasts to form new myofibers in in vitro assays.
      We isolated primary myoblasts from the quadriceps femoris of rhesus macaques that
      were administered CBA or isocaloric sucrose (SUC) for 19 mo. Proliferation and
      differentiation potential of cultured myoblasts were examined in vitro. Myoblasts
      from the CBA group had significantly reduced PAX7, MYOD1, MYOG, MYF5, and MEF2C
      expression. This was associated with decreased myotube formation as evidenced by
      Jenner-Giemsa staining and myonuclei fusion index. No significant difference in
      the proliferative ability, cell cycle distribution, or autophagy was detected
      between myoblasts isolated from CBA and SUC groups. Together, these results
      reflect marked dysregulation of myoblast myogenic gene expression and myotube
      formation, which we interpret as evidence of impaired skeletal muscle
      regenerative capacity in CBA-administered macaques. The contribution of this
      mechanism to alcoholic myopathy warrants further investigation.

PMID- 24671246
TI  - Health policy update 2014: another exciting and turbulent year ahead.

PMID- 24671245
TI  - Functional adaptation of bovine mesenteric lymphatic vessels to mesenteric venous
      hypertension.
AB  - Lymph flow is the primary mechanism for returning interstitial fluid to the blood
      circulation. Currently, the adaptive response of lymphatic vessels to mesenteric
      venous hypertension is not known. This study sought to determine the functional
      responses of postnodal mesenteric lymphatic vessels. We surgically occluded
      bovine mesenteric veins to create mesenteric venous hypertension to elevate
      mesenteric lymph flow. Three days after surgery, postnodal mesenteric lymphatic
      vessels from mesenteric venous hypertension (MVH; n = 7) and sham surgery (Sham;
      n = 6) group animals were evaluated and compared. Contraction frequency (MVH:
      2.98 +/- 0.75 min(-1); Sham: 5.42 +/- 0.81 min(-1)) and fractional pump flow
      (MVH: 1.14 +/- 0.30 min(-1); Sham: 2.39 +/- 0.32 min(-1)) were significantly
      lower in the venous occlusion group. These results indicate that postnodal
      mesenteric lymphatic vessels adapt to mesenteric venous hypertension by reducing
      intrinsic contractile activity.

PMID- 24671247
TI  - [Molecular lymph node staging in prostate and bladder cancer].
AB  - A positive lymph node status is a major prognostic factor for tumor recurrence
      and mortality following radical prostatectomy in prostate cancer patients or
      radical cystectomy in bladder cancer patients. However, despite having
      histopathologic negative lymph nodes, a substantial proportion of patient suffers
      from tumor recurrence within a few years after the operation. Tumor recurrence in
      node-negative patients may result from hematogeneous or lymphatic metastatic
      spread which remains undetected by standard clinical or histopathologic
      examinations. Molecular lymph node analysis is a potential method for detection
      of lymph node metastases with higher sensitivity and for prognostic risk
      stratification of patients with histopathologic negative lymph nodes.

PMID- 24671248
TI  - [Tumor cells in the peripheral blood of patients with urothelial carcinoma of the
      bladder: detection and impact of circulating].
AB  - Circulating tumor cells (CTC) play a crucial role in the natural history of
      several malignancies and, thus, are the subject of intense research efforts. This
      review summarizes the most contemporary literature data regarding detection of
      CTC and their impact on the oncological prognosis of patients with urothelial
      carcinoma of the bladder (UCB). Despite the availability of different methods for
      CTC detection and isolation in the peripheral blood, the standardized and Food
      and Drug Administration-approved CellSearch(r) assay is currently the most
      commonly used system for CTC detection. The majority of studies did not find any
      association between presence of CTC and clinicopathologic features. However, CTC
      have been demonstrated to represent a strong, independent predictor for
      unfavorable oncological outcomes in UCB. Since the peripheral blood is an easily
      accessible source, CTC represent a promising biomarker to effectively monitor
      early disease progression and therapy response in the near future. CTC hold the
      potential to individualize patient counseling regarding the optimal timing of
      radical surgery or bladder-sparing treatment as well as multimodal therapies. 

PMID- 24671249
TI  - [Detection of circulating tumor cells from peripheral blood in prostate cancer].
AB  - Circulating tumor cells (CTCs) can be detected with sensitive immunocytological
      and molecular methods and can potentially cause distant metastases. Consecutively
      the prognostic significance of CTC-counts for survival was demonstrated in
      metastatic prostate cancer (mPC) revealing CTCs as reliable surrogate marker
      during therapy. Comparatively the prognostic value of a CTC-threshold with < 5
      vs. >= 5 CTCs was superior to the commonly used PSA-decrement algorithms. In
      contrast despite evidence of CTCs in localized PC, their clinical value in this
      stage is currently precarious. Furthermore, CTCs may serve as predictive markers
      with the ability to predict treatment sensitivity or resistance, since they may
      represent the heterogeneous molecular signature of primary as well as metastatic
      cancer lesions. Thus, the isolation of CTCs may serve not only as a prognostic
      tool but moreover as a liquid biopsy and a window towards personalized treatment.
      This review discusses the clinical impact of CTCs in the different stages of PC.

PMID- 24671250
TI  - [Prostate and bladder cancer: detection of disseminated tumor cells in bone
      marrow].
AB  - The prognosis of prostate and bladder cancer patients is predominantly determined
      by the detection of distant sites of metastasis. In clinical routine, virtually
      only lymph node staging is of relevance to determine metastasis. Detection and
      characterization of disseminated tumor cells in peripheral blood or bone marrow
      is an additional parameter of prognostic significance. In this article, we will
      summarize recent progress on the prognostic value of disseminated tumor cells in
      bone marrow and its translation into routine clinical analysis. 

PMID- 24671252
TI  - Using the Aesop's fable paradigm to investigate causal understanding of water
      displacement by New Caledonian crows.
AB  - Understanding causal regularities in the world is a key feature of human
      cognition. However, the extent to which non-human animals are capable of causal
      understanding is not well understood. Here, we used the Aesop's fable paradigm-
      in which subjects drop stones into water to raise the water level and obtain an
      out of reach reward--to assess New Caledonian crows' causal understanding of
      water displacement. We found that crows preferentially dropped stones into a
      water-filled tube instead of a sand-filled tube; they dropped sinking objects
      rather than floating objects; solid objects rather than hollow objects, and they
      dropped objects into a tube with a high water level rather than a low one.
      However, they failed two more challenging tasks which required them to attend to
      the width of the tube, and to counter-intuitive causal cues in a U-shaped
      apparatus. Our results indicate that New Caledonian crows possess a
      sophisticated, but incomplete, understanding of the causal properties of
      displacement, rivalling that of 5-7 year old children.

PMID- 24671254
TI  - Cumulative risks of foster care placement by age 18 for U.S. children, 2000-2011.
AB  - Foster care placement is among the most tragic events a child can experience
      because it more often than not implies that a child has experienced or is at very
      high risk of experiencing abuse or neglect serious enough to warrant state
      intervention. Yet it is unclear how many children will experience foster care
      placement at some point between birth and age 18. Using synthetic cohort life
      tables and data from the Adoption and Foster Care Analysis and Reporting System
      (AFCARS), we estimated how many U.S. children were placed in foster care between
      birth and age 18, finding support for three conclusions. First, up to 5.91% of
      all U.S. children were ever placed in foster care between their birth and age 18.
      Second, Native American (up to 15.44%) and Black (up to 11.53%) children were at
      far higher risk of placement. Foster care is thus quite common in the U.S.,
      especially for historically disadvantaged racial/ethnic groups. Third,
      differences in foster care placement were minimal between the sexes, indicating
      that the high risks of foster care placement are shared almost equally by boys
      and girls. 

PMID- 24671255
TI  - Context consistency and seasonal variation in boldness of male two-spotted
      gobies.
AB  - In order to attribute the behaviour of an animal to its personality it is
      important to study whether certain behavioural traits show up consistently across
      a variety of contexts. The aim of this study was to investigate whether breeding
      state males of the two-spotted goby, Gobiusculus flavescens, showed consistent
      degree of boldness when tested in four different behaviour assays. We also wanted
      to investigate whether boldness varied over the breeding season in accordance
      with changes in male-male competition for matings. We used two standard assays
      (the emergence test and the open field test), and two simple assays related to
      threat response. Repeated runs of each of the tests were highly correlated, and
      we found significant correlations between all four assays. Thus, we have
      documented both a within and a between-context consistency in risk-taking
      behaviour. Furthermore, we found that goby males studied during the middle of the
      breeding season were bolder than males studied at the end of the season. Since
      male two-spotted gobies face strongly decreasing male-male competition as the
      season progresses, the benefit of being bold for the mating success of the males
      may differ over the time of the breeding season. The difference in behaviour
      found over the season thus corresponds well with the sexual dynamics of this
      model species. 

PMID- 24671253
TI  - Neuroprotective effect of TAT-14-3-3epsilon fusion protein against cerebral
      ischemia/reperfusion injury in rats.
AB  - Stroke is the major cause of death and disability worldwide, and the thrombolytic
      therapy currently available was unsatisfactory. 14-3-3epsilon is a well
      characterized member of 14-3-3 family, and has been reported to protect neurons
      against apoptosis in cerebral ischemia. However, it cannot transverse blood brain
      barrier (BBB) due to its large size. A protein transduction domain (PTD) of HIV
      TAT protein, is capable of delivering a large variety of proteins into the brain.
      In this study, we generated a fusion protein TAT-14-3-3epsilon, and evaluated its
      potential neuroprotective effect in rat focal ischemia/reperfusion (I/R) model.
      Western blot analysis validated the efficient transduction of TAT-14-3-3epsilon
      fusion protein into brain via a route of intravenous injection. TAT-14-3-3epsilon
      pre-treatment 2 h before ischemia significantly reduced cerebral infarction
      volume and improved neurologic score, while post-treatment 2 h after ischemia was
      less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3
      3epsilon significantly increased the number of surviving neurons as determined by
      Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the
      decrease in apoptotic cell numbers and the inhibition of caspase-3 activity.
      Moreover, the introduction of 14-3-3epsilon into brain by TAT-mediated delivering
      reduced the formation of autophagosome, attenuated LC3B-II upregulation and
      reversed p62 downregulation induced by ischemic injury. Such inhibition of
      autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP),
      which also attenuated the neuroprotective effect of TAT-14-3-3epsilon.
      Conversely, autophagy inhibitor 3-methyladenine (3-MA) inhibited I/R-induced the
      increase in autophagic activity, and attenuated I/R-induced brain infarct. These
      results suggest that TAT-14-3-3epsilon can be efficiently transduced into brain
      and exert significantly protective effect against brain ischemic injury through
      inhibiting neuronal apoptosis and autophagic activation. 

PMID- 24671256
TI  - Allogenic tooth transplantation inhibits the maintenance of dental pulp
      stem/progenitor cells in mice.
AB  - Our recent study suggested that allogenic tooth transplantation may affect the
      maintenance of dental pulp stem/progenitor cells. This study aims to elucidate
      the influence of allograft on the maintenance of dental pulp stem/progenitor
      cells following tooth replantation and allo- or auto-genic tooth transplantation
      in mice using BrdU chasing, immunohistochemistry for BrdU, nestin and Ki67, in
      situ hybridization for Dspp, transmission electron microscopy and TUNEL assay.
      Following extraction of the maxillary first molar in BrdU-labeled animals, the
      tooth was immediately repositioned in the original socket, or the roots were
      resected and immediately allo- or auto-grafted into the sublingual region in non
      labeled or the same animals. In the control group, two types of BrdU label
      retaining cells (LRCs) were distributed throughout the dental pulp: those with
      dense or those with granular reaction for BrdU. In the replants and autogenic
      transplants, dense LRCs remained in the center of dental pulp associating with
      the perivascular environment throughout the experimental period and possessed a
      proliferative capacity and maintained the differentiation capacity into the
      odontoblast-like cells or fibroblasts. In contrast, LRCs disappeared in the
      center of the pulp tissue by postoperative week 4 in the allografts. The
      disappearance of LRCs was attributed to the extensive apoptosis occurring
      significantly in LRCs except for the newly-differentiated odontoblast-like cells
      even in cases without immunological rejection. The results suggest that the host
      and recipient interaction in the allografts disturbs the maintenance of dense
      LRCs, presumably stem/progenitor cells, resulting in the disappearance of these
      cell types. 

PMID- 24671258
TI  - Halogen impact into new oxonium benzo-crown ether complexes with tetrachloro- and
      tetrabromoaurates(III).
AB  - Five oxonium tetrahalogenaurate(III) (Hal = Cl, Br) benzo-crown ether (BCE)
      complexes are prepared and reported. The new compounds are [(H3O)(B18C6)(0.58)(4'
      Cl-B18C6)0.42][AuCl4] 1, [(H3O)(B18C6)][AuCl4] 2, [(H3O)(4'-Br-B18C6)][AuCl4] 3,
      [(H3O)(4'-Br-B18C6)][AuBr4] 4, and [(H3O)(B18C6)][AuBr4] 5. The reaction medium,
      distinctive from the previously used aqua regia, allowed avoiding the unwanted
      nitration of initial macrocycles. The compositions and structures for 1, 3, 4,
      and 5 were proved by single crystal X-ray crystallography. The complete
      conversion of tetrachloroaurate(III) to the tetrabromoaurate(III) salts resulted
      in complex 4 isomorphous and isostructural to 3. All compounds form the laminated
      structures with alternation of cationic and anionic layers. The robustness of the
      anionic sheets is sustained by the halogen-halogen interactions and makes crucial
      impact on extraction of stoichiometric products in the case of
      tetrabromoaurate(III) salts.

PMID- 24671257
TI  - Effects of dextrose and lipopolysaccharide on the corrosion behavior of a Ti-6Al
      4V alloy with a smooth surface or treated with double-acid-etching.
AB  - Diabetes and infections are associated with a high risk of implant failure.
      However, the effects of such conditions on the electrochemical stability of
      titanium materials remain unclear. This study evaluated the corrosion behavior of
      a Ti-6Al-4V alloy, with a smooth surface or conditioned by double-acid-etching,
      in simulated body fluid with different concentrations of dextrose and
      lipopolysaccharide. For the electrochemical assay, the open-circuit-potential,
      electrochemical impedance spectroscopy, and potentiodynamic test were used. The
      disc surfaces were characterized by scanning electron microscopy and atomic force
      microscopy. Their surface roughness and Vickers microhardness were also tested.
      The quantitative data were analyzed by Pearson's correlation and independent t
      tests (alpha = 0.05). In the corrosion parameters, there was a strong
      lipopolysaccharide correlation with the Ipass (passivation current density), Cdl
      (double-layer capacitance), and Rp (polarization resistance) values (p<0.05) for
      the Ti-6Al-4V alloy with surface treatment by double-acid-etching. The
      combination of dextrose and lipopolysaccharide was correlated with the Icorr
      (corrosion current density) and Ipass (p<0.05). The acid-treated groups showed a
      significant increase in Cdl values and reduced Rp values (p<0.05, t-test).
      According to the topography, there was an increase in surface roughness (R2 =
      0.726, p<0.0001 for the smooth surface; R2 = 0.405, p = 0.036 for the double-acid
      etching-treated surface). The microhardness of the smooth Ti-6Al-4V alloy
      decreased (p<0.05) and that of the treated Ti-6Al-4V alloy increased (p<0.0001).
      Atomic force microscopy showed changes in the microstructure of the Ti-6Al-4V
      alloy by increasing the surface thickness mainly in the group associated with
      dextrose and lipopolysaccharide. The combination of dextrose and
      lipopolysaccharide affected the corrosion behavior of the Ti-6Al-4V alloy surface
      treated with double-acid-etching. However, no dose-response corrosion behavior
      could be observed. These results suggest a greater susceptibility to corrosion of
      titanium implants in diabetic patients with associated infections. 

PMID- 24671259
TI  - Lateral dislocation and incarceration of the posterior tibial tendon through the
      distal tibiofibular syndesmosis.
AB  - A case of acute, traumatic, lateral dislocation of the posterior tibial tendon is
      presented as a unique pattern of posterior tibial tendon dislocation. Several
      attempts at both closed and open reduction were required to relocate the tendon
      and reduce the fracture-dislocation. This case is being presented to demonstrate
      the use of cross-sectional imaging to both recognize the initial bony injury and
      to identify tendon anatomy and pathology that may not be seen in the operating
      room with limited visualization. 

PMID- 24671260
TI  - Synthesis of heteroboroxines with MB2O3 core (M = Sb, Bi, Sn)--an influence of
      the substitution of parent boronic acids.
AB  - The synthesis and structure of stiba-, stanna- and bismaheteroboroxines of a
      general formula L(E)M[(OBR)2O] supported by a N,C,N-chelating ligand L [where L =
      C6H3-2,6-(CH2NMe2)2, M, E = Sb, lone pair or Sn, Ph or Bi, lone pair] is
      reported. The target compounds are prepared by straightforward one-step reactions
      between oxides (LMO)2 (M = Sb or Bi) or organotin(iv) carbonate L(Ph)Sn(CO3) with
      four or two molar equivalents of corresponding organoboronic acid. All compounds
      were characterized with the help of elemental analysis, multinuclear NMR
      spectroscopy and on several occasions the molecular structure was determined
      using single-crystal X-ray diffraction analysis. The influence of both the
      substitution of the parent organoboronic acid and the central atom used on the
      feasibility of the condensation reaction was addressed. Furthermore, several
      heteroboroxines containing nitrogen donor functionality (i.e. NH2, NMe2, CN or 4
      pyridyl) included in the boronic acid residue were synthesized and characterized
      with the aim to prepare boroxine-based covalent frameworks (through
      intermolecular N->B interactions) containing metal atoms in their structures.
      Although no such intermolecular bonding was detected in solution of these
      compounds, it was shown that the organotin(iv) heteroboroxine substituted by 4
      pyridyl group forms an infinite polymeric chains via N->B interactions in the
      solid state. This polymer collapsed back to monomeric units upon dissolution. 

PMID- 24671261
TI  - Voltammetric pH sensor based on an edge plane pyrolytic graphite electrode.
AB  - A simple sensor for pH determination is reported using unmodified edge plane
      pyrolytic graphite (EPPG) electrodes. The analysis is based on the electro
      reduction of surface quinone groups on the EPPG which was characterised using
      cyclic voltammetry (CV) and optimised with square-wave voltammetry (SWV). Under
      optimised conditions, a linear response is observed between the peak potential
      and pH with a gradient of ~59 mV per pH (at 25  degrees C), which corresponds
      well with Nernstian behaviour based on a 2 proton, 2 electron system over the
      aqueous pH range 1.0 to 13.0. As such, an EPPG is suggested as a reagent free and
      robust pH sensing material. 

PMID- 24671262
TI  - Coffee: biochemistry and potential impact on health.
AB  - This review provides details on the phytochemicals in green coffee beans and the
      changes that occur during roasting. Key compounds in the coffee beverage,
      produced from the ground, roasted beans, are volatile constituents responsible
      for the unique aroma, the alkaloids caffeine and trigonelline, chlorogenic acids,
      the diterpenes cafestol and kahweol, and melanoidins, which are Maillard reaction
      products. The fate of these compounds in the body following consumption of coffee
      is discussed along with evidence of the mechanisms by which they may impact on
      health. Finally, epidemiological findings linking coffee consumption to potential
      health benefits including prevention of several chronic and degenerative
      diseases, such as cancer, cardiovascular disorders, diabetes, and Parkinson's
      disease, are evaluated. 

PMID- 24671263
TI  - Age-dependent changes of nuclear morphology are uncoupled from longevity in
      Caenorhabditis elegans IGF/insulin receptor daf-2 mutants.
AB  - Nuclear envelope (NE) architecture and aging have been associated since the
      discovery that certain human progeria diseases are due to perturbations in
      processing of lamin A protein, generating alterations in NE morphology. However,
      whether changes in the NE are a causal effect of normal and premature aging is
      still controversial. Caenorhabditis elegans is a model organism where
      observations supporting both, dependent and independent roles of nuclear
      architecture in the aging process, have been reported. We found that the long
      lived glp-1 mutant and dietary restriction delayed age-associated nuclear
      morphology changes. In addition, we observed that the long-lived mutant of the
      insulin/IGF receptor daf-2 delayed the age-dependent changes of nuclear
      architecture at 25  degrees C, as previously described. However, when daf-2
      animals were incubated at 20  degrees C they remained long-lived, but nuclear
      appearance changed at similar rate as in the wild type. This supports the idea
      that both phenotypes, longevity and maintenance of nuclear architecture are
      tightly associated but can be separated and argues that nuclear morphology
      deterioration is not a cause of the natural aging process. 

PMID- 24671264
TI  - High-dimensional single-cell cancer biology.
AB  - Cancer cells are distinguished from each other and from healthy cells by features
      that drive clonal evolution and therapy resistance. New advances in high
      dimensional flow cytometry make it possible to systematically measure mechanisms
      of tumor initiation, progression, and therapy resistance on millions of cells
      from human tumors. Here we describe flow cytometry techniques that enable a
      "single-cell " view of cancer. High-dimensional techniques like mass cytometry
      enable multiplexed single-cell analysis of cell identity, clinical biomarkers,
      signaling network phospho-proteins, transcription factors, and functional
      readouts of proliferation, cell cycle status, and apoptosis. This capability
      pairs well with a signaling profiles approach that dissects mechanism by
      systematically perturbing and measuring many nodes in a signaling network. Single
      cell approaches enable study of cellular heterogeneity of primary tissues and
      turn cell subsets into experimental controls or opportunities for new discovery.
      Rare populations of stem cells or therapy-resistant cancer cells can be
      identified and compared to other types of cells within the same sample. In the
      long term, these techniques will enable tracking of minimal residual disease
      (MRD) and disease progression. By better understanding biological systems that
      control development and cell-cell interactions in healthy and diseased contexts,
      we can learn to program cells to become therapeutic agents or target malignant
      signaling events to specifically kill cancer cells. Single-cell approaches that
      provide deep insight into cell signaling and fate decisions will be critical to
      optimizing the next generation of cancer treatments combining targeted approaches
      and immunotherapy. 

PMID- 24671265
TI  - Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems
      in recurrent pregnancy loss.
AB  - PURPOSE: Both vascular endothelial growth factor A (VEGFA) and endocrine gland
      derived vascular endothelial growth factor (EG-VEGF) systems play major roles in
      angiogenesis. A body of evidence suggests VEGFs regulate critical processes
      during pregnancy and have been associated with recurrent pregnancy loss (RPL).
      However, little information is available regarding the interaction of these two
      major major angiogenesis-related systems in early human pregnancy. This study was
      conducted to investigate the association of gene polymorphisms and gene-gene
      interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. METHODS:
      A total of 98 women with history of idiopathic RPL and 142 controls were
      included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1
      and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR)
      analysis to choose a best model and evaluate gene-gene interactions. Ingenuity
      pathways analysis (IPA) was introduced to explore possible complex interactions.
      RESULTS: Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were
      significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that
      the KDR (Q472H) polymorphism was the best loci to be associated with RPL
      (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical
      signaling pathways that may contribute to gene-gene interactions, including the
      Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. CONCLUSION:
      Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were
      significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared
      several canonical signaling pathways that may contribute to gene-gene
      interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

PMID- 24671266
TI  - Developmental capacity and pregnancy rate of tetrahedral- versus non-tetrahedral
      shaped 4-cell stage human embryos.

PMID- 24671268
TI  - Surface-confined core-shell structures based on gold nanoparticles and metal
      organic networks.
AB  - Here we show a step-wise approach for the formation of continuous shell
      structures on surface-confined gold nanoparticles. The nanoparticle-cores induce
      order in the shell-structure, which consists of metal-organic networks.
      Communication between the organic and inorganic parts is reflected in their
      optical properties. 

PMID- 24671267
TI  - Additive effect of heat on the UVB-induced tyrosinase activation and
      melanogenesis via ERK/p38/MITF pathway in human epidermal melanocytes.
AB  - Heat is known as an environmental factor that causes significant skin
      pigmentation, but its effects on melanogenesis have been poorly studied. It has
      been shown that mitogen-activated protein kinase (MAPK) is involved in
      ultraviolet B (UVB) and stress-induced melanogenesis in melanocytes. In this
      study, we investigated the effects of heat and UVB, on melanocyte melanogenesis,
      differentiation, and MAPK phosphorylation. The results showed that heat (1 h at
      40  degrees C for 5 days) increased cell dendrites, enlarged cell bodies, and
      induced extracellular signal-regulated kinases (ERK)/p38/MITF activation but did
      not influence melanogenesis of human epidermal melanocytes from skin phototype
      III. UVB irradiation (20 mJ/cm(2) for 5 days) induced melanogenesis and c-jun N
      terminal kinases (JNK)/p38/MITF/tyrosinase activation in melanocytes from skin
      phototype III. UVB combined with heat resulted in much more significant
      tyrosinase activation and melanogenesis as compared with UVB alone in melanocytes
      from skin phototype III. Furthermore, heat treatment and UVB irradiation induced
      JNK, ERK, and p38 activation but not melanogenic and morphological changes in
      melanocytes from skin phototype I. These findings suggested that heat promoted
      melanocyte differentiation, probably via heat-induced ERK/p38/MITF/activation.
      Furthermore, heat had an additive effect on the UVB-induced tyrosinase activation
      and melanogenesis. These results provide a new clue for dermatologists for the
      treatment of hypopigmented skin disease with heat combined with UVB irradiation.

PMID- 24671269
TI  - Cancerous cell targeting and destruction using pH stabilized amperometric
      bioconjugated gold nanoparticles from marine macroalgae, Padina gymnospora.
AB  - The main aim of this study was, using biomechanistic approach, to synthesize and
      characterize amperometric stable gold nanoparticles (AuNPs) under different pH
      conditions using UV Spec, dynamic light scattering and TEM with energy dispersive
      X-ray analysis. The biomolecules involved in conjugation and reduction were
      further characterized by Fourier transform infrared analysis. The pH stabilized
      nanoparticles were studied to determine the functional and molecular mechanism of
      cell death on liver cancer (HepG2) cell line and gastric cancer (YCC3) cell line.
      The zeta potential and TEM imaging demonstrated that AuNPs were spherical in
      nature and can pass through the cellular membrane because of their intrinsic
      properties of AuNPs to bind to carbon-bonded sulfhydryl (-C-SH or R-SH) group
      and, therefore, could interact with intracellular components of the cell which
      was confirmed through phase contrast microscopy. Altered molecular mechanism and
      cellular effects in different cancer cell suggest a potential for in vivo
      applications of gold nanomaterials. 

PMID- 24671270
TI  - The optimized CO2-added ammonia explosion pretreatment for bioethanol production
      from rice straw.
AB  - A CO2-added ammonia explosion pretreatment was performed for bioethanol
      production from rice straw. The pretreatment conditions, such as ammonia
      concentration, CO2 loading level, residence time, and temperature were optimized
      using response surface methodology. The response for optimization was defined as
      the glucose conversion rate. The optimized pretreatment conditions resulting in
      maximal glucose yield (93.6 %) were determined as 14.3 % of ammonia
      concentration, 2.2 MPa of CO2 loading level, 165.1  degrees C of temperature, and
      69.8 min of residence time. Scanning electron microscopy analysis showed that
      pretreatment of rice straw strongly increased the surface area and pore size,
      thus increasing enzymatic accessibility for enzymatic saccharification. Finally,
      an ethanol yield of 97 % was achieved via simultaneous saccharification and
      fermentation. Thus, the present study suggests that CO2-added ammonia
      pretreatment is an appropriate process for bioethanol production from rice straw.

PMID- 24671271
TI  - Model-based design and integration of a two-step biopharmaceutical production
      process.
AB  - This paper presents the design of a two-step process in which the first step is
      PEGylation of a protein, and the second step is chromatographic purification of
      the target mono-PEGylated protein from the unreacted and the di-PEGylated
      impurities. The difference between optimizing each process step separately and
      optimizing them simultaneously is studied. It was found that by optimizing the
      steps simultaneously up to a 100 % increase in productivity could be obtained
      without reduction in yield. Optimizing both steps at the same time makes it
      possible for the optimization method to take into account that the di-PEGylated
      protein is much easier to separate than the non-PEGylated protein. The easier
      separation makes it possible to get a higher yield and productivity at the same
      time. The effect of recycling was also studied and the yield could be increased
      by 30 % by recycling the unreacted protein. However, if maximum productivity is
      required, batch mode is preferable. 

PMID- 24671272
TI  - Development of uniform density control with self-assembled colloidal gold
      nanoparticles on a modified silicon substrate.
AB  - Here, we present a simple method for controlling the density of Au nanoparticles
      (Au NPs) on a modified silicon substrate, by destabilizing the colloidal Au NPs
      with 3-mercaptopropyltrimethoxylsilane (3-MPTMS) for microelectromechanical
      system-based applications to reduce tribological issues. A silicon surface was
      pretreated with a 3-MPTMS solution, immediately after which thiolated Au NPs were
      added to it, resulting in their uniform deposition on the silicon substrate.
      Without any material property change of the colloidal Au NPs, we observed the
      formation of large clusters Au NPs on the modified silicon surface. Analysis by
      scanning electron microscopy with energy dispersive X-ray spectroscopy indicated
      that the addition of 3-MPTMS resulted in an alternation of the chemical
      characteristics of the solution. Atomic force microscopy imaging supported the
      notion that silicon surface modification is the most important factor on
      tribological properties of materials along with ligand-modified Au NPs. The
      density of Au NPs on a silicon surface was significantly dependent on several
      factors, including the concentration of colloidal Au NPs, deposition time, and
      concentration of 3-MPTMS solution, while temperature range which was used
      throughout experiment was determined to have no significant effect. A relatively
      high density of Au NPs forms on the silicon surface as the concentrations of Au
      NPs and 3-MPTMS are increased. In addition, the maximum deposition of Au NPs on
      silicon wafer was observed at 3 h, while the effects of temperature variation
      were minimal. 

PMID- 24671273
TI  - Maternal insulin sensitivity is associated with oral glucose-induced changes in
      fetal brain activity.
AB  - AIMS/HYPOTHESIS: Fetal programming plays an important role in the pathogenesis of
      type 2 diabetes. The aim of the present study was to investigate whether maternal
      metabolic changes during OGTT influence fetal brain activity. METHODS: Thirteen
      healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was
      determined by glucose and insulin measurements at 0, 60 and 120 min. At each time
      point, fetal auditory evoked fields were recorded with a fetal
      magnetoencephalographic device and response latencies were determined. RESULTS:
      Maternal insulin increased from a fasting level of 67 +/- 25 pmol/l (mean +/- SD)
      to 918 +/- 492 pmol/l 60 min after glucose ingestion and glucose levels increased
      from 4.4 +/- 0.3 to 7.4 +/- 1.1 mmol/l. Over the same time period, fetal response
      latencies decreased from 297 +/- 99 to 235 +/- 84 ms (p = 0.01) and then remained
      stable until 120 min (235 +/- 84 vs 251 +/- 91 ms, p = 0.39). There was a
      negative correlation between maternal insulin sensitivity and fetal response
      latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median
      split of the group based on maternal insulin sensitivity, fetuses of insulin
      resistant mothers showed a slower response to auditory stimuli (283 +/- 79 ms)
      than those of insulin-sensitive mothers (178 +/- 46 ms, p = 0.03).
      CONCLUSIONS/INTERPRETATION: Lower maternal insulin sensitivity is associated with
      slower fetal brain responses. These findings provide the first evidence of a
      direct effect of maternal metabolism on fetal brain activity and suggest that
      central insulin resistance may be programmed during fetal development.

PMID- 24671275
TI  - Dialysis-treated end-stage kidney disease in Libya: epidemiology and risk
      factors.
AB  - PURPOSE: End-stage kidney disease (ESKD) is now a worldwide pandemic. In concert
      with this, ESKD in Libya has also increased exponentially in recent decades. This
      review aims to define the magnitude of and risks for this ESKD epidemic among
      Libyans as there is a dearth of published data on this subject. METHODS: A
      systematic review was conducted by searching PubMed, EMBASE and Google scholar
      databases to identify all relevant papers published in English from 2003 to 2012,
      using the following keywords: end stage, terminal, chronic, renal, kidney, risk
      factors, Arab, North Africa and Libya. RESULTS: In 2003, the reported incidence
      of ESKD and prevalence of dialysis-treated ESKD in Libya were the same at 200 per
      million population (pmp). In 2007, the prevalence of dialysis-treated ESKD was
      350 pmp, but the true incidence of ESKD was not available. The most recent
      published WHO data in 2012 showed the incidence of dialysis-treated ESKD had
      risen to 282 pmp and the prevalence of dialysis-treated ESKD had reached 624 pmp.
      The leading causes of ESKD were diabetic kidney disease (26.5 %), chronic
      glomerulonephritis (21.1 %), hypertensive nephropathy (14.6 %) and
      congenital/hereditary disease (12.3 %). The total number of dialysis centers was
      40 with 61 nephrologists. Nephrologist/internist to patient ratio was 1:40, and
      nurse to patient ratio was 1:3.7. Only 135 living-related kidney transplants had
      been performed between 2004 and 2007. There were no published data on most
      macroeconomic and renal service factors. CONCLUSIONS: ESKD is a major public
      health problem in Libya with diabetic kidney disease and chronic
      glomerulonephritis being the leading causes. The most frequent co-morbidities
      were hypertension, obesity and the metabolic syndrome. In addition to provision
      of RRT, preventive strategies are also urgently needed for a holistic integrated
      renal care system.

PMID- 24671277
TI  - Widening gaps in the wall obscuring physician performance differences.

PMID- 24671278
TI  - Supramolecular interactions induced hinge-like motion of a metal-organic
      framework accompanied by anisotropic thermal expansion.
AB  - A novel three-dimensional metal-organic framework (MOF), Ag4(tpt)4{delta
      [Mo8O26]}.1.5H2O (A) (tpt = 2,4,6-tris(4-pyridyl)-1,3,5-triazine), possesses a
      ths-type topology with the hinge deformation mode. The single-crystal X-ray
      diffraction study shows that A and the dehydrated phase Ag4(tpt)4{delta-[Mo8O26]}
      (B) display distinct anisotropic thermal expansion with expansion in the b
      direction but contraction in the ac plane. This rare area negative thermal
      expansion (NTE) behavior is attributed to the hinged structure model and the
      supramolecular interactions (argentophilic interaction, pi-pi interaction) that
      act as the microscopic driving forces. In addition, supramolecular interactions
      also play a key role in thermochromic behavior of compound A.

PMID- 24671279
TI  - Intraoperative irreversible deformation of Allergan's style 410 breast implant.

PMID- 24671276
TI  - Sexually dimorphic expression of vasa isoforms in the tongue sole (Cynoglossus
      semilaevis).
AB  - The vasa gene encodes an ATP-dependent RNA helicase of the DEAD box protein
      family that functions in a broad range of molecular events involving duplex RNA.
      In most species, the germline specific expression of vasa becomes a molecular
      marker widely used in the visualization and labeling of primordial germ cells
      (PGCs) and a tool in surrogate broodstock production through PGC transplantation.
      The vasa gene from tongue sole (Cynoglossus semilaevis) was characterized to
      promote the development of genetic breeding techniques in this species. Three C.
      semilaevis vasa transcripts were isolated, namely vas-l, vas-m, and vas-s.
      Quantitative real-time PCR results showed that C. semilaevis vasa transcripts
      were prevalently expressed in gonads, with very weak expression of vas-s in other
      tissues. Embryonic development expression profiles revealed the onset of zygotic
      transcription of vasa mRNAs and the maternal deposit of the three transcripts.
      The genetic ZW female juvenile fish was discriminated from genetic ZZ males by a
      pair of female specific primers. Only the expression of vas-s can be observed in
      both sexes during early gonadal differentiation. Before PGCs started mitosis,
      there was sexually dimorphic expression of vas-s with the ovary showing higher
      levels and downward trend. The results demonstrated the benefits of vasa as a
      germline specific marker for PGCs during embryonic development and gonadal
      differentiation. This study lays the groundwork for further application of C.
      semilaevis PGCs in fish breeding. 

PMID- 24671280
TI  - Nasal tip suspending transfixion suture.
AB  - BACKGROUND: Anterior septal height is an important determinant of nasal tip
      projection. Accordingly, the anterior septal extension technique has proven
      itself to be a powerful tool for achieving long-lasting nasal tip projection in
      rhinoplasty. However, anterior septal extension does not protect against
      postoperative loss of nasal tip rotation unless an additional suspension strategy
      is used. A tip-suspending transfixion suture is the authors' strategy for
      supporting nasal tip rotation whenever an anterior septal extension technique is
      performed. METHODS: Of 156 rhinoplasties performed by the authors between 2010
      and 2012, a cohort of 22 droopy-tip rhinoplasties was extracted in which the
      described technique was used. The patients in this cohort were included in a
      retrospective nasal tip projection and rotation analysis. The nasolabial angle
      (NLA) and Goode ratio measurements were compared between preoperative, 3-week
      postoperative, and 1-year postoperative profile-view photographs. RESULTS: The
      NLA and the Goode ratio measurements were significantly higher in the 3-week
      postoperative group than in the preoperative group, indicating an effective gain
      in both tip projection and rotation. The NLA and the Goode ratio measurements did
      not differ statistically between the postoperative 3-week and postoperative 1
      year groups, indicating long-term maintenance of nasal tip position. CONCLUSION:
      A tip-suspending transfixion suture is an easy method for securing nasal tip
      rotation when used in conjunction with an anterior septal extension. LEVEL OF
      EVIDENCE V: This journal requires that authors assign a level of evidence to each
      article. For a full description of these Evidence-Based Medicine ratings, please
      refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24671281
TI  - A stable metallic state of (TTPCOO)2NH4 with a mobile dopant.
AB  - Ammonium tetrathiapentalene carboxylate [(TTPCOO)2NH4] was prepared via protonic
      defect-induction doping without electrochemical oxidation. The high electric
      conductivity of 13 S cm(-1) and Pauli paramagnetic-like behavior of magnetic
      susceptibility in a wide temperature range exhibit a melting of the charge
      degrees of freedom induced by a mobile dopant in a salt bridge. Solid-state (1)H
      NMR strongly indicates a stable metallic state of this compound down to 4 K. 

PMID- 24671282
TI  - Furthering orthodontic research?

PMID- 24671283
TI  - Commentaries.

PMID- 24671284
TI  - Translation and validation of a Nepalese version of the Psychosocial Impact of
      Dental Aesthetic Questionnaire (PIDAQ).
AB  - OBJECTIVE: The aim of this study was to develop a reliable and valid Nepali
      version of the Psychosocial Impact of Dental Aesthetic Questionnaire (PIDAQ).
      DESIGN: Cross-sectional descriptive validation study. SETTINGS: B.P. Koirala
      Institute of Health Sciences, Dharan, Nepal. METHODS: A rigorous translation
      process including conceptual and semantic evaluation, translation, back
      translation and pre-testing was carried out. Two hundred and fifty-two
      undergraduates, including equal numbers of males and females with an age ranging
      from 18 to 29 years (mean age: 22.33+/-2.114 years), participated in this study.
      Reliability was assessed by Cronbach's alpha coefficient and the coefficient of
      correlation was used to assess correlation between items and test-retest
      reliability. The construct validity was tested by factorial analysis. Convergent
      construct validity was tested by comparison of PIDAQ scores with the aesthetic
      component of the index of orthodontic treatment needs (IOTN-AC) and perception of
      occlusion scale (POS), respectively. Discriminant construct validity was assessed
      by differences in score for those who demand treatment and those who did not.
      RESULTS: The response rate was 100%. One hundred and twenty-three individuals had
      a demand for orthodontic treatment. The Nepali PIDAQ had excellent reliability
      with Cronbach's alpha of 0.945, corrected item correlation between 0.525 and
      0.790 and overall test-retest reliability of 0.978. The construct validity was
      good with formation of a new sub-domain 'Dental self-consciousness'. The scale
      had good correlation with IOTN-AC and POS fulfilling convergent construct
      validity. The discriminant construct validity was proved by significant
      differences in scores for subjects with demand and without demand for treatment.
      CONCLUSION: To conclude, Nepali version of PIDAQ has good psychometric properties
      and can be used effectively in this population group for further research.

PMID- 24671285
TI  - Localization of ectopic maxillary canines -- is CBCT more accurate than
      conventional horizontal or vertical parallax?
AB  - OBJECTIVE: To compare the accuracy of cone-beam CT (CBCT) with conventional
      horizontal and vertical parallax for the localization of ectopic maxillary
      canines. DESIGN: Observational study. METHODS: A typodont was constructed using
      human teeth embedded in radio-dense impression material, containing a simulated
      ectopic canine. Image sets (vertical/horizontal parallax and CBCT scans) were
      obtained for nine positions. A photograph confirmed the true position of the
      canine. Six observers used horizontal (HP) and vertical (VP) parallax techniques
      with conventional radiographs and the axial, coronal and sagittal CBCT views to
      locate the canine tip. Images were manipulated as required using proprietary
      software (http://www.carestream.com and http://www.i-cat.com). Intra-observer
      reproducibility was calculated by one observer re-evaluating the image sets after
      2 months. Individual observer validity was calculated in relation to the
      photographic position of the canine using weighted Kappa. Differences in the
      proportion of correct locations between CBCT and vertical/horizontal parallax
      were tested using McNemar tests (P<0.05). RESULTS: Intra- and inter-observer
      agreements were excellent (0.8985) and substantial (0.7528), respectively.
      Individual observer validity was substantial-excellent (0.7368-0.900). The canine
      position was correctly identified in 94% of cases located using CBCT, 83% using
      HP and 65% using VP. The differences between CBCT and vertical and horizontal
      parallax were highly statistically significant (P<0.01). CONCLUSION: CBCT is more
      accurate than either horizontal or vertical parallax for the localization of
      ectopic maxillary canine teeth.

PMID- 24671286
TI  - A 3D analysis of Caucasian and African American facial morphologies in a US
      population.
AB  - INTRODUCTION: This study aimed to compare facial morphologies of an adult African
      American population to an adult Caucasian-American population using three
      dimensional (3D) surface imaging. MATERIALS AND METHODS: The images were captured
      using a stereophotogrammetric system (3dMDface(TM) system). Subjects were aged 19
      30 years, with normal body mass index and no gross craniofacial anomalies. Images
      were aligned and combined using RF6 Plus Pack 2 software to produce a male and
      female facial average for each population. The averages were superimposed and the
      differences were assessed. RESULTS: The most distinct differences were in the
      forehead, alar base and perioricular regions. The average difference between
      African-American and Caucasian-American females was 1.18+/-0.98 mm. The African
      American females had a broader face, wider alar base and more protrusive lips.
      The Caucasian-American females had a more prominent chin, malar region and lower
      forehead. The average difference between African-American and Caucasian-American
      males was 1.11+/-1.04 mm. The African-American males had a more prominent upper
      forehead and periocular region, wider alar base and more protrusive lips. No
      notable difference occurred between chin points of the two male populations.
      CONCLUSIONS: Average faces were created from 3D photographs, and the facial
      morphological differences between populations and genders were compared. African
      American males had a more prominent upper forehead and periocular region, wider
      alar base and more protrusive lips. Caucasian-American males showed a more
      prominent nasal tip and malar area. African-American females had broader face,
      wider alar base and more protrusive lips. Caucasian-American females showed a
      more prominent chin point, malar region and lower forehead.

PMID- 24671287
TI  - Comparison of residual monomer loss from cold-cure orthodontic acrylic resins
      processed by different polymerization techniques.
AB  - INTRODUCTION: This investigation aimed to assess and compare the amount of
      residual monomer (RM) released from removable orthodontic appliances constructed
      by sprinkle-on and dough techniques. MATERIALS AND METHODS: One hundred and
      twenty acrylic samples were prepared from orthodontic autopolymerized acrylic
      resins and divided into three groups, according to the processing method:
      sprinkle-on with polyclave, sprinkle-on without polyclave and dough technique.
      After polymerization, the specimens of each group were immersed in distilled
      water for 24 h, 48 h, 72 h and 1 week. High-performances liquid chromatography
      (HPLC) was utilized to measure residual monomer content. RESULTS: Maximum
      observed RM was 1284.91+/-129.07 ppm measured for sprinkle-on technique without
      polyclave after 24 h of water immersion. At this time, the level of RM was
      significantly different among the three applied techniques (P<0.05). In all
      soaking time groups, sprinkle-on technique with polyclave released the least
      amount of RM. Within each group, the maximum monomer releasing was observed after
      the first 24 h and decreases were observed in subsequent time groups. The
      reduction over the time was not significant in the polyclave groups (P>0.05).
      CONCLUSION: The sprinkle-on technique with polyclave and longer water immersion
      reduced residual monomer released from acrylic orthodontic appliances.

PMID- 24671289
TI  - Natural pontics.
AB  - Temporary pontics are a popular strategy to hide tooth extraction sites ('black
      holes') during course of the orthodontic treatment, especially with lingual
      appliances. Here, we describe a technique for using the patient's extracted
      premolar as a temporary pontic. 

PMID- 24671288
TI  - Orthodontic treatment of a stubborn palatally ectopic canine: a case report.
AB  - This is a case report that highlights a different treatment approach in dealing
      with palatally ectopic canines. The modified transpalatal arch with an 'active'
      arm was used to align a palatally ectopic canine with 'push' mechanics after the
      initial use of more conventional 'pull' mechanics (piggy-back archwire technique)
      had failed. 

PMID- 24671290
TI  - Orthodontic skeletal anchorage using a palatal external plate.
AB  - We have developed the Anchor-Lock external plate system, which is fitted on the
      palate for the purpose of orthodontic skeletal anchorage. The aim of this study
      was to introduce the Anchor-Lock and assess its success rate. The Anchor-Lock is
      composed of titanium screws of 2.0-mm diameter and a titanium plate of 1.0-mm
      thickness. The external plate is rigidly interlocked with the heads of the
      screws, which are implanted trans-mucosally into palatal bone. Three types of
      Anchor-Lock are available. These were applied to 137 orthodontic patients (104
      females and 33 males) aged 10-54 years. Two types of plate were used, a straight
      shaped plate applied to the hard palate and to the anterior palate and a double-Y
      shaped plate applied after tooth-borne rapid maxillary expansion. Success rate of
      the Anchor-Lock was 92.0% overall. No significant difference in success rate was
      found by age or sex of patients. Type or screw length of the Anchor-Lock did not
      affect success rate significantly. Success rate was significantly increased by
      the use of the surgical stent. The Anchor-Lock was effectively applied to
      distalize and/or intrude the upper molars. The Anchor-Lock system appears
      suitable for clinical use as an alternative to conventional screw- and plate-type
      orthodontic implants. 

PMID- 24671295
TI  - Anti-cancer therapeutic potential of quinazoline based small molecules via global
      upregulation of miRNAs.
AB  - Three quinazoline based small molecules showed global upregulation of miRNA
      expression with a selective enrichment of tumor suppressor miRNAs. The target
      genes of the upregulated miRNAs were predicted to be enriched for apoptotic
      pathways. Apoptotic induction following treatment with quinazoline compounds was
      confirmed by in cellulo studies. Thus, these small molecules having the core
      structural moiety (2,4-diphenyl-quinazoline) can be used as scaffolds to design
      activators of miRNA expression paving the way for novel anti-cancer drugs. 

PMID- 24671296
TI  - Revisiting heart activation-conduction physiology, part I: atria.
AB  - This discussion paper re-examines the conduction-activation of the atria, based
      on observations, with respect to the complexity of the heart as an organ with a
      brain, and its evolution from a peristaltic tube. The atria do not require a
      specialized conduction system because they use the subendocardial layer to
      produce centripetal transmural activation fronts, regardless of the anatomical
      and histological organization of the transmural atrial wall. This has been
      described as "two-layer" physiology which provides robust transmission of
      activation from the sinus to the AV node via a centripetal transmural activation
      front. New productive insights can come from re-examining the physiology, not
      only during sinus rhythm but also during atrial tachycardias, in particular
      atrial flutter and atrial fibrillation (AF). During common flutter, the areas of
      slow conduction, in the isthmus and following trabeculations, particularly the
      subendocardial layer confines conduction through the trabeculations which
      supports re-entry. During experimental or postoperative flutter, the circular 2D
      activation around the obstacle follows the physiological transmural activation.
      Understanding this physiology offers insights into AF. During acute or protracted
      AF, the presence of stationary or drifting rotors is characteristic and
      consistent with normal physiological 2D atrial activation, suggesting that
      suppressing physiological transmural activation of AF will permanently restore
      normal sinus node atrial activation. In contrast, during permanent AF, normal 2D
      activation is abolished; the presence of transmural, serpentine, and chaotic
      atrial activation suggests that the normal physiological activation pattern has
      been replaced by a new, irreversible variety of atrial conduction that is a new
      physiology, which is consistent with evolution of complex systems. 

PMID- 24671297
TI  - A strong adsorbent for Cu2+: graphene oxide modified with triethanolamine.
AB  - A strong adsorbent TEA-GO for Cu(2+) is prepared using TEA modified GO
      nanosheets. FT-IR and XPS results show that epoxy groups on GO are eliminated,
      and simultaneously hydroxyl groups and C-N dominate the surface groups of TEA-GO.
      The increased equilibrium capacity of TEA-GO for a high initial concentration of
      Cu(2+) makes it a promising adsorbent for heavy metal ions. 

PMID- 24671298
TI  - Comparison of 16S rRNA sequencing with biochemical testing for species-level
      identification of clinical isolates of Neisseria spp.
AB  - We aimed to compare accuracy of genus and species level identification of
      Neisseria spp. using biochemical testing and 16S rRNA sequence analysis. These
      methods were evaluated using 85 Neisseria spp. clinical isolates initially
      identified to the genus level by conventional biochemical tests and API NH system
      (Bio-Merieux((r))). In 34 % (29/85), more than one possibility was given by 16S
      rRNA sequence analysis. In 6 % (5/85), one of the possibilities offered by 16S
      rRNA gene sequencing, agreed with the result given by biochemical testing. In 4 %
      (3/85), the same species was given by both methods. 16S rRNA gene sequencing
      results did not correlate well with biochemical tests.

PMID- 24671299
TI  - Crude bacterial extracts of two new Streptomyces sp. isolates as bio-colorants
      for textile dyeing.
AB  - Renewed demand for incorporation of natural dyes (bio-colorants) in textile
      industry could be met through biotechnological production of bacterial pigments.
      Two new Streptomyces strains (NP2 and NP4) were isolated for the remarkable
      ability to produce diffusible deep blue and deep red pigment into fermentation
      medium. Crude mycelial extracts of both strains were used as bio-colorants in
      conventional textile dyeing procedures avoiding downstream purification
      procedures. The yields of bio-colorants obtained in this way were 62 and 84 mg
      per g of mycelia for Streptomyces sp. NP2 and Streptomyces sp. NP4, respectively.
      Through nuclear magnetic resonance analysis of crude extracts before and after
      dyeing procedures, it was shown that both extracts contained prodigiosin-like
      family of compounds that exhibited different dyeing capabilities towards
      different textile fibers. Polyamide and acrylic fibers were colored to the
      deepest shade, polyester and triacetate fibers to a noticeable, but much lower
      shade depth, while cotton and cellulosic fibers stained weakly. These results
      confirmed that crude bacterial extracts had the characteristics similar to those
      of ionic and disperse dyes, which was consistent with the identified polypyrrolic
      prodigiosin-like structures.

PMID- 24671300
TI  - Lactonase-expressing Lactobacillus plantarum NC8 attenuates the virulence factors
      of multiple drug resistant Pseudomonas aeruginosa in co-culturing environment.
AB  - Pseudomonas aeruginosa possesses an arcade of both cell-associated and
      extracellular cytotoxic virulence factors which are regulated by a multi
      component quorum sensing system. Many research studies report success of
      lactonase in combating the pathogenicity of P. aeruginosa but delivery of
      lactonase remains a challenge. The present study aims at developing a delivery
      vehicle for lactonase. Lactobacillus plantarum NC8 was used as host for aiiA
      (Bacillus thuringiensis 4A3 lactonase gene) using pSIP409 expression vector.
      pSIP409: aiiA construct was stably maintained in L. plantarum NC8. Co-culturing
      of multi-drug resistant (MDR) clinical isolates of P. aeruginosa and PAO1 with
      recombinant L. plantarum NC8 led to significant reduction (p < 0.001) in
      extracellular virulence factors like pyocyanin, protease, elastase and
      rhamnolipids in P. aeruginosa and also showed significant reduction in adhesion
      of P. aeruginosa strains to uroepithelial cells in vitro. This study shows the
      heterologous expression of AiiA lactonase in L. plantarum NC8. Co-culturing of
      lactonase expressing L. plantarum NC8 with MDR P. aeruginosa strains led to
      attenuation of their virulence significantly. These results underscore the
      potential application of recombinant L. plantarum NC8 with anti-quorum sensing
      properties to control infections caused by multidrug resistant P. aeruginosa.

PMID- 24671301
TI  - Revisiting the guidelines issued by the Japanese Society of Thyroid Surgeons and
      Japan Association of Endocrine Surgeons: a gradual move towards consensus between
      Japanese and western practice in the management of thyroid carcinoma.
AB  - BACKGROUND: In 2010, the Japanese Society of Thyroid Surgeons (JSTS) and Japanese
      Association of Endocrine Surgeons (JAES) established new guidelines entitled
      "Treatment of Thyroid Tumors." Since then, several new studies, including those
      that address the treatment of differentiated thyroid carcinoma (DTC) have been
      published, and the DTC treatment policy not only of Japanese physicians but those
      in Western countries has continued to evolve. METHODS: We selected six clinical
      questions regarding the treatment of DTC and revisited them based on newly
      published data from Western countries and Japan. RESULTS: More data have
      accumulated about treatment of low-risk papillary microcarcinoma. It has become
      clear that conservative treatment (observation) of low-risk papillary
      microcarcinoma in elderly patients is an acceptable alternative to immediate
      surgery. Total thyroidectomy versus hemithyroidectomy for low-risk papillary
      thyroid carcinoma (PTC) has become an important issue, and some publications
      after 2010 indicated that hemithyroidectomy is adequate for these low-risk
      patients. Unfortunately, no published manuscripts on prophylactic central node
      dissection offered good evidence regarding its indications or included a large
      number of patients. Also, it was not evident that prophylactic lateral node
      dissection improves cause-specific survival, although it might reduce lymph node
      recurrence especially in PTC patients with large tumors, distant metastases, or
      clinical central node metastases. Although completion total thyroidectomy was not
      recommended for minimally invasive follicular thyroid carcinoma in our
      guidelines, it may be better to perform it in elderly patients and those with a
      large tumor or extensive vascular invasion. Radioactive iodine (RAI) ablation
      after total thyroidectomy is still performed almost routinely in many Western
      institutions, although recent studies showed that ablation is not beneficial in
      low-risk patients. In Japan, because of legal restrictions, most patients did not
      undergo RAI ablation, and their prognoses are excellent. CONCLUSIONS: Recently,
      policy for treating DTCs has changed not only in Western countries but also in
      Japan, resulting in a gradual move toward consensus between Western practice and
      ours. We will continue to present the best treatments for patients with thyroid
      carcinoma each time we revise our guidelines.

PMID- 24671302
TI  - Outcome of tumor-specific mesorectal excision for rectal cancer: the impact of
      laparoscopic resection.
AB  - OBJECTIVE: The study aimed to compare the outcomes of laparoscopic and open
      resection for rectal cancer in 1,063 consecutive cases in a single center.
      METHODS: We performed an analysis of 11 years of experience in rectal cancer
      surgery and compared the outcome of laparoscopic and open surgery. Multivariate
      and subgroup analysis was performed to look at the effect of the level of tumor
      and stage of disease on short-term outcomes like conversion rate, anastomotic
      leak rate, length of stay, complication rate, 30-day mortality, and long-term
      outcomes like local recurrence and survival. RESULTS: A total of 1,063 patients
      underwent rectal resection with 470 (44.2%) patients undergoing the laparoscopic
      approach. Groups were comparable in terms of age, sex, or co-morbidities, and the
      operating time was longer in the laparoscopic group (210 vs. 150 min; p value <
      0.001). A conversion rate of 6.8% was noted, with an anastomotic leak rate of
      3.87% in the open group and 2.97% in the laparoscopic group. The laparoscopic
      group had a lower blood loss (100 vs. 350 ml; p < 0.001), lower complication
      rates, and shorter length of stay (6 vs. 9 days). The local recurrence rate was
      comparable, and the laparoscopic approach had better overall and cancer-specific
      survival, even after adjusting for stages. The laparoscopic approach was an
      independent factor associated with better overall and cancer-specific survival on
      multivariate analysis. CONCLUSION: We confirmed the oncological safety of
      laparoscopic rectal cancer surgery. Laparoscopic surgery also showed superiority
      in the short-term and long-term outcomes of rectal cancer.

PMID- 24671303
TI  - Discovery of new druggable sites in the anti-cholesterol target HMG-CoA reductase
      by computational alanine scanning mutagenesis.
AB  - The enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA-R) is the
      fundamental target for the treatment of hypercholesterolemia nowadays. The HMG
      CoA-R clinical active site inhibitors (statins) are among the most widespread and
      profitable drugs ever sold but their side effects (myopathies, sometimes severe)
      still limit their use, which makes the finding of alternatives to statins a field
      of intense research. In this line, we address here a new strategy for inhibiting
      the homotetrameric HMG-CoA-R. The enzyme consists of a "dimer of dimers", each
      dimer having two active sites. We pursue here the inhibition of enzyme
      oligomerization, through drug binding to the dimer interface. We have
      computationally mutated 232 interfacial residues by alanine and calculated the
      loss in binding free energy among the monomers that build up each dimer of the
      homotetramer. This led to the identification of the (ten) key residues for the
      formation of the active dimer (Glu528, Ile531, Met534, Tyr644, Glu665, Asn686,
      Lys692, Lys735, Met742, and Val863). The results show that these residues are
      located in two specific spots of the protein with a cleft shape, whose shape and
      size is favorable for small drug binding. It is expectable that small molecules
      specifically bound to these druggable pockets will have a major effect on the
      oligomerization of the protein or/and in active site formation. This paves the
      way for the discovery of new families of inhibitors of HMG-CoA-R. 

PMID- 24671304
TI  - Implementing electrostatic polarization cannot fill the gap between experimental
      and theoretical measurements for the ultrafast fluorescence decay of myoglobin.
AB  - Over the past few years, time-dependent ultrafast fluorescence spectroscopy
      method has been applied to the study of protein dynamics. However, observations
      from these experiments are in a controversy with other experimental studies.
      Participating of theoretical methods in this debate has not reconciled the
      contradiction, because the predicted initial relaxation from computer simulations
      is one-order faster than the ultrafast fluorescence spectroscopy experiment. In
      those simulations, pairwise force fields are employed, which have been shown to
      underestimate the roughness of the free energy landscape. Therefore, the
      relaxation rate of protein and water molecules under pairwise force fields is
      falsely exaggerated. In this work, we compared the relaxations of
      tryptophan/environment interaction under linear response approximation employing
      pairwise, polarized, and polarizable force fields. Results show that although the
      relaxation can be slowed down to a certain extent, the large gap between
      experiment and theory still cannot be filled. 

PMID- 24671305
TI  - Lead and trace element levels in milk and blood of buffaloes (Bubalus bubalis)
      from Hyderabad, India.
AB  - The presence of lead (Pb) in milk and its interaction with trace elements is a
      serious health concern. Present study is aimed at determining Pb and trace
      element (Fe, Zn and Mg) levels in milk and blood/serum samples of lactating
      buffaloes (Bubalus bubalis) living in a market-area (Group-A) and a dairy
      experimental station (Group-B), Hyderabad, India. In addition, kidney and liver
      function tests were assessed. Fodder, milk and blood Pb levels were significantly
      (p < 0.01) higher in Group-B. Elevated Pb levels correlated positively with
      reduced Fe and Zn levels in both serum and milk. A significant (p < 0.01)
      positive correlation between blood Pb and milk Pb levels was observed. Kidney and
      liver function markers were significantly higher in Group-B buffaloes. The
      results suggest that contaminated fodder might be one of the responsible factors
      for elevated Pb levels. In addition, lower levels of Fe and Zn might have led to
      bioaccumulation of Pb in blood and milk.

PMID- 24671306
TI  - Copper-dependent inhibition and oxidative inactivation with affinity cleavage of
      yeast glutathione reductase.
AB  - Effects of copper on the activity and oxidative inactivation of yeast glutathione
      reductase were analyzed. Glutathione reductase from yeast was inhibited by cupric
      ion and more potently by cuprous ion. Copper ion inhibited the enzyme
      noncompetitively with respect to the substrate GSSG and NADPH. The Ki values of
      the enzyme for Cu(2+) and Cu(+) ion were determined to be 1 and 0.35 MUM,
      respectively. Copper-dependent inactivation of glutathione reductase was also
      analyzed. Hydrogen peroxide and copper/ascorbate also caused an inactivation with
      the cleavage of peptide bond of the enzyme. The inactivation/fragmentation of the
      enzyme was prevented by addition of catalase, suggesting that hydroxyl radical
      produced through the cuprous ion-dependent reduction of oxygen is responsible for
      the inactivation/fragmentation of the enzyme. SDS-PAGE and TOF-MS analysis
      confirmed eight fragments, which were further determined to result from the
      cleavage of the Met17-Ser18, Asn20-Thr21, Glu251-Gly252, Ser420-Pro421, Pro421
      Thr422 bonds of the enzyme by amino-terminal sequencing analysis. Based on the
      kinetic analysis and no protective effect of the substrates, GSSG and NADPH on
      the copper-mediated inactivation/fragmentation of the enzyme, copper binds to the
      sites apart from the substrate-sites, causing the peptide cleavage by hydroxyl
      radical. Copper-dependent oxidative inactivation/fragmentation of glutathione
      reductase can explain the prooxidant properties of copper under the in vivo
      conditions.

PMID- 24671307
TI  - Sperm bundles in the seminal vesicles of sexually mature Lasius ant males.
AB  - In many insects, sperm cells are produced in bundles with their heads being held
      together by a glycoprotein matrix secreted by a cyst cell. Mature sperm cells in
      the seminal vesicles are usually free, but in sawflies and several other insects,
      such structures (spermatodesmata) remain intact and sperm cells may be ejaculated
      as bundles. Here we report the occurrence of spermatodesmata in mature males of
      the ant Lasius pallitarsis. Microscopic investigations of the abdominal contents
      of males immediately prior to their nuptial flights showed that the anterior ends
      of numerous sperm cells were embedded in an oval-shaped 20 by 30 micrometer
      extracellular fibrous cap. Individual sperm ranged in length from 55 to 75
      micrometers with an average overall length of 65 micrometers. The bulb-shaped
      heads of the sperm were relatively small, only about 1.5 micrometers in length
      and about 1.1 micrometers in diameter. The diameter of the sperm tails was
      approximately 1 micrometer. Observations of live preparations of the
      spermatodesmata showed increasingly active undulating wave-like movement of the
      sperm tails as the slide preparations aged. This appears to be the first case of
      sperm bundles being present in the seminal vesicles of mature ant males--males
      that are immediately poised to complete their nuptial mating flight.

PMID- 24671308
TI  - Right lower quadrant pain during pregnancy.

PMID- 24671310
TI  - Tetrahydropentalenyl-phosphazene constrained geometry complexes of rare-earth
      metal alkyls.
AB  - Reactions of CpTMHPPh2 (1, diphenyl(4,4,6,6-tetramethyl-1,4,5,6
      tetrahydropentalen-2-yl)phosphane) with the organic azides AdN3 and DipN3 (Ad = 1
      adamantyl; Dip = 2,6-di-iso-propylphenyl) led to the formation of two novel CpPN
      ligands: P-amino-cyclopentadienylidene-phosphorane (CpTMPPh2NHAd; L(Ad)H) and P
      cyclopentadienyl-iminophosphorane (CpTMHPPh2NDip; L(Dip)H). Both were
      characterized by NMR spectroscopy and X-ray structure analysis. For both
      compounds only one isomer was observed. Neither possesses any detectable
      prototropic or elementotropic isomers. Reactions of these ligands with
      [Lu(CH2SiMe3)3(thf)2] or with rare-earth metal halides and three equivalents of
      LiCH2SiMe3 produced the desired bis(alkyl) CpTMPN complexes:
      [{CpTMPN}M(CH2SiMe3)2] (M = Sc (1(Ad), 1(Dip)), Lu (2(Ad), 2(Dip)), Y (3(Ad),
      3(Dip)), Sm (4(Ad)), Nd (5(Ad)), Pr (6(Ad)), Yb (7(Ad))). These complexes were
      characterized by extensive NMR studies for the diamagnetic and the paramagnetic
      complexes with full signal assignment. An almost mirror inverted order of the
      paramagnetic shifts has been observed for ytterbium complex 7(Ad) compared to
      4(Ad), 5(Ad) and 6(Ad). For the assignment of the NMR signals [{eta(1) : eta(5)
      C5Me4PMe2NAd}Yb(CH2SiMe3)2] 7 was synthesized, characterized and the (1)H NMR
      signals were compared to 7(Ad) and to other paramagnetic lanthanide complexes
      with the same ligand. 1(Ad), 2(Ad), 2(Dip), 3(Ad) and 3(Dip) were characterized
      by X-ray structure analysis revealing a sterically congested constrained geometry
      structure.

PMID- 24671311
TI  - Polysomnographic differences associated with pulmonary hypertension in patients
      with advanced lung disease due to cystic fibrosis.
AB  - BACKGROUND: Pulmonary hypertension (PH) commonly occurs in patients with cystic
      fibrosis (CF), but there is no current data regarding alterations of sleep in
      patients with PH. METHODS: A single-center, retrospective review was performed in
      patients with advanced lung disease due to CF who completed both nocturnal
      polysomnography and right heart catheterization (RHC) from January 2010 to June
      2013. For statistical analysis, two-tailed unpaired t tests and Pearson
      correlation coefficient analysis were performed after normal distribution was
      confirmed. RESULTS: A total of 18 consecutive CF patients were enrolled with RHC
      identifying PH in 56 % (10/18) of patients. The PH group had significantly lower
      mean sleep efficiency (72 +/- 4 vs. 87 +/- 3 %, p = 0.01), significantly higher
      ETCO(2) levels (54.5 +/- 2.2 vs. 43.8 +/- 3.0 mmHg, p = 0.01) on capnography, and
      significantly lower PO(2) (53.8 +/- 3.1 vs. 65.5 +/- 3.9 mmHg, p = 0.03) on
      capillary blood gas. Correlations with poor sleep efficiency included mean PAP (r
      = - 0.55, p = 0.01), systolic PAP (r = -0.5, p = 0.03), ETCO(2) (r = - 0.53, p =
      0.02), and PO(2)) (r = 0.62, p = 0.01); ETCO(2) with systolic PAP (r = 0.47, p =
      0.04) and PCO(2) (r = - 0.57, p = 0.01); and PO(2) to 6-min walk distance (r =
      0.55, p = 0.02). CONCLUSIONS: We found significant differences in sleep
      efficiency and gas exchange associated with PH in CF patients with advanced lung
      disease.

PMID- 24671312
TI  - Reductive generation of stable, five-membered N,N'-diamidocarbenes.
AB  - The synthesis of the first stable, five-membered N,N'-diamidocarbenes (DACs),
      including a differentially N-substituted derivative, was achieved via the
      reduction of a geminal dichloride precursor using potassium. Key differences
      between the reactivity of the five-membered DACs and their six-membered congeners
      were observed, including an ability to insert into electron-rich C-H bonds. 

PMID- 24671313
TI  - Fabrication of a hollow bulb prosthesis for the rehabilitation of an acquired
      total maxillectomy defect.
AB  - The prosthodontic rehabilitation of maxillary defects is a challenging and
      demanding task which requires careful pre-surgical and post-surgical planning.
      Maxillary defects can be congenital or acquired. Acquired defects include those
      following trauma or surgical treatment of benign or malignant neoplasms. A
      prosthodontist encounters problems such as absence of support, poor retention,
      and lack of prosthesis stability in treating these patients. The present case
      report describes a procedure to fabricate a definitive hollow bulb obturator
      prosthesis for the rehabilitation of a total maxillectomy defect. 

PMID- 24671314
TI  - Liver involvement in tuberous sclerosis.
AB  - Tuberous sclerosis complex (TSC) is a rare inherited disease that affects many
      organs and tissues, which explains the diversity of its clinical manifestations.
      This disease is often diagnosed at an early age when cutaneous angiofibromas,
      epilepsy and mental retardation are associated. The hepatic involvement in this
      phakomatosis is an uncommon location. In this context, we report the case of a
      tuberous sclerosis revealed in adulthood by abdominal pain and distension related
      to renal and hepatic angiomyolipomas associated with typical skin lesions. 

PMID- 24671315
TI  - Swimming with the fishes.

PMID- 24671316
TI  - Spontaneous hymeneal endometriosis: a rare cause of dyspareunia.
AB  - Vulvar endometriosis can occur after surgery or trauma and cause dyspareunia. A
      30-year-old woman presented with orificial dyspareunia lasting for 5 months. Her
      history was marked by a vaginal birth without perineal injury and the removal of
      a cyst from the left Bartholin's gland. On examination, we observed a selectively
      painful, superficial and retractile lesion, 5 mm in diameter at the junction of
      the hymen at some distance from the bartholinitis scar. Endometriosis was
      suspected due to the exacerbation of pain during menses. The surgery consisted of
      excision of the hymenal area of the painful lesion. Pathological examination
      confirmed the presence of endometrial tissue. The painful symptoms resolved and
      no additional treatment was administered. Any vulvar lesion, regardless of its
      appearance and location, can be related to endometriosis. Surgical resection is
      recommended to relieve the symptoms and provide histological proof. 

PMID- 24671317
TI  - Renal abscesses in childhood: report of two uncommon cases.
AB  - Renal abscesses are rare conditions in children, but they must be remembered in
      differential diagnosis of fever and abdominal pain. The authors report two
      paediatric cases with unusual presentation. Case 1: a 15-year-old girl was
      admitted following a period of fever, vomiting and left hypochondrium pain which
      became more localised to the left lower ribs. Blood tests suggested bacterial
      infection, but urinalysis and culture were negative. Renal CT scan presented
      features of bilateral pyelonephritis and left renal abscesses, while ultrasound
      remained normal until the ninth day of disease. Case 2: a 2-year-old girl, with
      diagnosis of beta-thalassemia minor, had intermittent diffuse abdominal pain with
      2 weeks of evolution. Renal ultrasonography and CT scan showed a heterogeneous
      mass compatible with Willms tumour. Intraoperative diagnosis was compatible with
      renal abscess with isolation of Proteus mirabilis in the fluid. Both responded
      well to long-term antibiotics and to surgical drainage (in the second case). 

PMID- 24671318
TI  - Successful pregnancy in a woman with paraplegia.
AB  - Pregnancy is a rare occurrence in patients suffering from spinal cord injury
      (SCI). Pregnancy in these patients presents unique challenges to obstetric care
      providers, who need to become familiar with the general principles of care in
      this setting. SCI alters the function of multiple organ systems and chronic
      medical conditions are common in this patient population. Certain medical
      complications such as urinary tract infections and autonomic hyper-reflexia, or
      autonomic dysreflexia, are expectable and can be managed successfully. A
      multidisciplinary team should care for delivery in these patients. The authors
      present a case of a pregnancy in a paraplegic woman whose lesion was at the level
      of T4. She received epidural analgesia and had a caesarian section. From this
      case, the authors aim to point out the specific concerns of the management of
      pregnancy and delivery in this setting emphasising the importance of a
      multidisciplinary team, specially obstetricians and anaesthetists. 

PMID- 24671319
TI  - An AIDS-defining neoplasm in a 30-year-old man on highly active antiretroviral
      therapy: a forgotten diagnosis?
AB  - Highly active antiretroviral therapy (HAART) has dramatically improved the
      morbidity and mortality of patients with HIV. Although the incidence of AIDS
      defining neoplasms is decreasing with this therapy, they must still be considered
      in patients who present with suspicious symptoms. Early diagnosis and treatment
      may help to improve quality of life and clinical outcome. We report the case of a
      30-year-old man on HAART who presented with an expanding lump in the left groin,
      thought to be a haematoma for 5 months. A high level of suspicion led to a prompt
      diagnosis of Burkitt's lymphoma followed by timely treatment with chemotherapy.
      This culminated in complete remission, with an improved quality of life. 

PMID- 24671320
TI  - Helicobacter pylori-negative Russell body gastritis: does the diagnosis call for
      screening for plasmacytic malignancies, especially multiple myeloma?
AB  - Russell body gastritis (RBG) is a rare entity with unestablished pathophysiology,
      endoscopic findings, clinical manifestations and treatments. Literature is scarce
      on this clinical entity with unclear clinical significance. Of 18 cases reported,
      12 tested (+) for Helicobacter pylori and improved with treatment, but it remains
      unclear whether this link is coincidental or bears some clinical significance. We
      describe a case of elderly woman who had a follow-up oesophagogastroduodenoscopy
      for chronic peptic ulcers, and biopsy showed positive immunohistochemical stains
      for kappa and lambda, indicating a polytypic population of plasma cells.
      Immunostaining for H pylori was negative. Biopsies were also (-) for gastric
      carcinoma, lymphoma and plasmacytoma. Considering her RGB-suggestive histology
      and her symptoms of bone pains and anaemia, multiple myeloma screening was
      considered clinically relevant. The purpose of this review was to educate
      clinicians and gastroenterologists about this unique entity and explore its
      association with multiple myeloma or other plamacytic malignancies.

PMID- 24671321
TI  - The importance of genetic mutation screening to determine retransplantation
      following failed kidney allograft from recurrent atypical haemolytic ureamic
      syndrome.
AB  - We report the case of a patient with familial atypical haemolytic uraemic
      syndrome (aHUS) who underwent successful retransplantation 30 months following
      his failed first kidney allograft from recurrent aHUS. He achieved excellent
      graft function (creatinine 90 MUmol/L), with no evidence of disease recurrence on
      standard maintenance immunosuppression 9 months after his second deceased donor
      kidney transplantation. Genetic mutation testing was not available prior to first
      transplant but screening prior to retransplant identified the patient as having a
      newly discovered mutation, c.T3566A, within exon 23 of the complement factor H
      (CFH) gene. Currently, public financing and subsidisation for eculizumab, a
      costly but effect complement (C5) inhibitor for the treatment of aHUS is not
      available in Australia. The decision for retransplantation must balance between
      the risk of disease recurrence and greater risk of death on dialysis. The absence
      of a more severe CFH genotype assisted in the decision for retransplantation and
      suggests the importance of genetic mutation screening in order to stratify the
      risk of disease recurrence and graft loss versus the benefit of transplantation. 

PMID- 24671322
TI  - Treating neuromyelitis optica with the interleukin-6 receptor antagonist
      tocilizumab.
AB  - We present a 32-year-old female patient with fulminant neuromyelitis optica.
      After the initial treatment with the monoclonal antibody rituximab failed,
      therapy with the anti-IL-6 receptor antagonist tocilizumab was initiated. The
      patient experienced a clinically relevant improvement from severe tetraparesis to
      low-grade paresis, which is still maintained. On MRI of the spinal cord an almost
      complete restitution of a predescribed extensive myelopathy accompanied this
      clinical improvement. Meanwhile clinical stability was achieved for over 1 year
      without any side effects of the ongoing treatment with tocilizumab. 

PMID- 24671323
TI  - Filling the void: a case of sepsis following the injection of a penile bulking
      agent.
AB  - Many cosmetic procedures are now performed by non-medical personnel. Owing to the
      wide coverage of aesthetic procedures by the media, patients may be less informed
      of the serious complications that can be seen when impure materials are injected
      by less-skilled practitioners. The authors present a case of sepsis following the
      injection of a non-medical grade penile bulking agent. Although penile
      augmentation is under-reported in the literature, public interest in such
      procedures is increasing. The growing demand for such procedures needs to be
      addressed by the medical community. 

PMID- 24671324
TI  - Necrotising fasciitis after bortezomib and dexamethasone-containing regimen in an
      elderly patient of Waldenstrom macroglobulinaemia.
AB  - Bortezomib and high-dose dexamethasone-containing regimens are considered to be
      generally tolerable with few severe bacterial infections in patients with B-cell
      malignancies. However, information is limited concerning the safety of the
      regimen in elderly patients. We report a case of a 76-year-old man with
      Waldenstrom macroglobulinaemia who suffered necrotising fasciitis without
      neutropenia after the combination treatment with bortezomib, high-dose
      dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy,
      he succumbed 23 h after the onset. Physicians should recognise the possibility of
      fatal bacterial infections related to bortezomib plus high-dose dexamethasone in
      elderly patients, and we believe this case warrants further investigation. 

PMID- 24671325
TI  - A surprising content of congenital hernia: complete splenogonadal fusion band.
AB  - Splenogonadal fusion is a rare congenital anomaly. We present the case of a 6
      year-old boy who presented with a left inguinoscrotal swelling. With a clinical
      diagnosis of left congenital inguinal hernia the patient was taken up for
      explorative laparotomy where a transperitoneal band was noted adherent to the
      left testis. Biopsy revealed normal splenic tissue. Postoperatively the boy was
      imaged and a diagnosis of splenogonadal fusion was made. This article illustrates
      the imaging features of this rare anomaly. 

PMID- 24671326
TI  - A radical treatment for surfer's eye.

PMID- 24671328
TI  - Neonatal non-laparoscopic non-robotic pneumovesical distension presenting as
      acute abdomen.

PMID- 24671327
TI  - A massive retroperitoneal neuroblastoma with stenosis of the inferior vena cava
      in a 5-month-old boy.
AB  - Neuroblastoma is the second most common retroperitoneal tumour in children after
      Wilms' tumour. When it originates in the retroperitoneum, neuroblastoma usually
      presents as an abdominal mass with clinical manifestations of nausea, vomiting
      and weight loss. Imaging studies of this tumour demonstrate a heterogeneous mass
      with an irregular capsule and visible calcifications. Encasement and compression
      of the abdominal vessels, especially the inferior vena cava, are often observed.
      However, stenosis of the inferior vena cava has never been reported to be
      associated with this tumour. Here, we present a case of a 5-month-old boy with a
      right retroperitoneal tumour with extensive encasement of the inferior vena cava
      and significant narrowing of its distal part between the venous bifurcation and
      the tumour capsule. To our knowledge, this is the first case of neuroblastoma
      with this manifestation in a child. 

PMID- 24671329
TI  - pH-Responsive and near-infrared-emissive polymer nanoparticles for simultaneous
      delivery, release, and fluorescence tracking of doxorubicin in vivo.
AB  - Dextran modified with pendant acetals is used to load doxorubicin (DOX) and a
      near-infrared-emissive conjugated polymer (BTTPF), and this aims to provide
      selective drug release at therapeutic targets including tumors. The BTTPF is
      applicable to tracking the anticancer drug release through the change of Forster
      resonance energy transfer efficiency between doxorubicin and BTTPF during
      degradation of the nanoparticles in vivo. 

PMID- 24671330
TI  - Facile synthesis of highly fluorescent BF2 complexes bearing isoindolin-1-one
      ligand.
AB  - Stable organoboron complexes as classic fluorescent molecules have found various
      applications in biotechnology and material sciences. A new class of isoindolin-1
      one based BF2 complexes containing pyridine or benzothiazole groups has been
      prepared from a facile "one-pot" reaction and characterized structurally,
      spectroscopically and electrochemically. These novel dyes show broad and intense
      absorption and emission bands in solution with high fluorescence quantum yields.
      Significantly larger Stokes shifts and higher photostability were observed for
      these dyes in comparison to those of classical BODIPYs. 

PMID- 24671331
TI  - Development of a novel calcium phosphate cement composed mainly of calcium sodium
      phosphate with high osteoconductivity.
AB  - Two novel calcium phosphate cements (CPC) have been developed using calcium
      sodium phosphate (CSP) as the main ingredient. The first of these cements,
      labeled CAC, contained CSP, alpha-tricalcium phosphate (TCP), and anhydrous
      citric acid, whereas the second, labeled CABC, contained CSP, alpha-TCP, beta
      TCP, and anhydrous citric acid. Biopex((r))-R (PENTAX, Tokyo, Japan), which is a
      commercially available CPC (Com-CPC), and OSferion((r)) (Olympus Terumo
      Biomaterials Corp., Tokyo, Japan), which is a commercially available porous beta
      TCP, were used as reference controls for analysis. In vitro analysis showed that
      CABC set in 5.7 +/- 0.3 min at 22  degrees C and had a compressive strength of
      86.0 +/- 9.7 MPa after 5 days. Furthermore, this material had a compressive
      strength of 26.7 +/- 3.7 MPa after 2 h in physiologic saline. CAC showed a
      statistically significantly lower compressive strength in the presence of
      physiologic saline and statistically significantly longer setting times than
      those of CABC. CABC and CAC exhibited apatite-forming abilities in simulated body
      fluid that were faster than that of Com-CPC. Samples of the materials were
      implanted into the femoral condyles of rabbits for in vivo analysis, and
      subsequent histological examinations revealed that CABC exhibited superior
      osteoconductivity and equivalent bioresorbability compared with Com-CPC, as well
      as superior osteoconductivity and bioresorbability compared with CAC. CABC could
      therefore be used as an alternative bone substitute material.

PMID- 24671332
TI  - Bioactive magnetic nanoparticles of Fe-Ga synthesized by sol-gel for their
      potential use in hyperthermia treatment.
AB  - Hyperthermia is one of the most recents therapies for cancer treatment using
      particles with nanometric size and appropriate magnetic properties for destroying
      cancer cells. Magnetic nanoparticles (MNP's) of Fe-Ga and synthesized using a
      polycondensation reaction by sol-gel method were obtained. MNP's of
      Fe(1.4)Ga(1.6)O(4) that possess an inverse spinel structure were identified by X
      Ray Diffraction, Transmission Electron Microscopy, Scanning Electron Microscopy
      and Energy Dispersive Spectroscopy. The results showed that the MNP's are
      composed only by Fe, Ga and O and their size is between 15 and 20 nm. The
      magnetic properties measured by Vibration Sample Magnetometry demonstrated a
      saturation magnetization value of 37.5 emu/g. To induce the MNP's bioactivity, a
      biomimetic method was used which consisted in the immersion of MNP's in a
      Simulated Body Fluid (SBF) for different periods of time (7, 14 and 21 d) along
      with a wollastonite disk. The formation of a bioactive layer, which closely
      resembles that formed on the existing bioactive systems and with a Ca/P atomic
      ratio within a range of 1.37-1.73 was observed on the MNP's. Cytotoxicity of
      MNP's was evaluated by in vitro hemolysis testing using human red blood cells at
      concentrations between 0.25 and 6.0 mg/mL. It was found that the MNP's were not
      cytotoxic at none of the concentrations used. The results indicate that Fe-Ga
      MNP's are potential materials for cancer treatment of both hard and soft tissue
      by hyperthermia and drug carriers, among other applications.

PMID- 24671333
TI  - Albumin inhibits the insulin-mediated ACE2 increase in cultured podocytes.
AB  - Podocytes are key cells in the glomerular filtration barrier with a major role in
      the development of diabetic nephropathy. Podocytes are insulin-sensitive cells
      and have a functionally active local renin-angiotensin system. The presence and
      activity of angiotensin-converting enzyme 2 (ACE2), the main role of which is
      cleaving profibrotic and proinflammatory angiotensin-II into angiotensin-(1-7),
      have been demonstrated in podocytes. Conditionally immortalized mouse podocytes
      were cultured with insulin in the presence and absence of albumin. We found that
      insulin increases ACE2 gene and protein expression, by real-time PCR and Western
      blotting, respectively, and enzymatic activity within the podocyte and these
      increases were maintained over time. Furthermore, insulin favored an "anti
      angiotensin II" regarding ACE/ACE2 gene expression balance and decreased
      fibronectin gene expression as a marker of fibrosis in the podocytes, all studied
      by real-time PCR. Similarly, insulin incubation seemed to protect podocytes from
      cell death, studied by a terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling assay. However, all these effects disappeared in the presence of
      albumin, which may mimic albuminuria, a main feature of DN pathophysiology. Our
      results suggest that modulation of renin-angiotensin system balance, fibrosis,
      and apoptosis by insulin in the podocyte may be an important factor in preventing
      the development and progression of diabetic kidney disease, but the presence of
      albuminuria seems to block these beneficial effects. 

PMID- 24671334
TI  - OMA1 mediates OPA1 proteolysis and mitochondrial fragmentation in experimental
      models of ischemic kidney injury.
AB  - Acute kidney injury (AKI) is associated with mitochondrial fragmentation, which
      contributes to mitochondrial damage and tubular cell apoptosis. Mitochondrial
      fragmentation involves the cleavage of both mitochondrial outer and inner
      membranes. Cleavage of the outer membrane results from Drp-1-mediated fission
      activation and Bak-promoted fusion arrest, but the molecular mechanism of inner
      membrane cleavage remains elusive. OMA1-mediated proteolysis of OPA1, a key inner
      membrane fusion protein, was recently suggested to account for inner membrane
      cleavage during cell stress. In this study, we determined the role of OMA1 in
      OPA1 proteolysis and mitochondrial fragmentation in experimental models of
      ischemic AKI. In ATP-depletion injury, knockdown of OMA1 suppressed OPA1
      proteolysis, mitochondrial fragmentation, cytochrome c release, and consequent
      apoptosis in renal proximal tubular cells. In mice, OMA1 deficiency prevented
      ischemic AKI as indicated by better renal function, less tubular damage, and
      lower apoptosis. OPA1 proteolysis and mitochondrial injury during ischemic AKI
      were ameliorated in OMA1-deficient mice. Thus, OMA1-mediated OPA1 proteolysis
      plays an important role in the disruption of mitochondrial dynamics in ischemic
      AKI. 

PMID- 24671335
TI  - Morphometric study of mandibular foramen in macerated skulls to contribute to the
      development of sagittal split ramus osteotomy (SSRO) technique.
AB  - PURPOSE: The aim of this study was to provide morphometric data, obtained from
      macerated mandibles, which might facilitate the topographic location of the
      mandibular foramen, considering aspects such as gender, age and ethnicity.
      MATERIALS AND METHODS: One hundred and eighty-five macerated mandibles of adult
      black and white individuals of both sexes were analyzed. Initially, 5 points were
      established: MF, the lowest point of the mandibular foramen; S, greatest
      concavity of the mandibular notch; A, anterior margin of the ramus of mandible;
      P, posterior margin of the ramus of mandible; and Go, gonion. Then the following
      measurements were performed bilaterally: MF-S, MF-A, MF-P and MF-Go. RESULTS: The
      following mean values were found: MF-S: 21.02 mm for white females (WF) and 22.00
      mm for black females (BF); 24.40 mm for white males (WM) and 24.35 mm for black
      males (BM); MF-A: 17.05 mm for WF and 18.09 mm for BF; 17.18 mm for WM and 18.11
      mm for BM; MF-P: 11.11 mm for WF and 12.24 mm for BF; 13.10 mm for WM and 14.15
      mm for BM; MF-Go: 19.00 mm for WF and 19.44 mm for BF; 23.13 mm for WM and 22.12
      mm for BM. CONCLUSIONS: The values found in this study, considering gender, age
      and ethnic group, can be used as a parameter to carry out the sagittal split
      ramus osteotomy technique, making it more predictable and with less risk of
      complications.

PMID- 24671336
TI  - Proximal ulna morphometry: which are the "true" anatomical preshaped olecranon
      plates?
AB  - PURPOSE: To define the optimum design of the anatomical preshaped olecranon
      plate. METHODS: The geometry of the proximal ulna was studied in 200 paired
      Caucasian ulnae, using a digital caliper and goniometer. Gender and side
      differences were analyzed. Results were compared with the corresponding
      geometrical parameters of three olecranon plates with different contour. All
      three plates were placed on the dorsal surface of a "model" ulna, i.e., a right
      dried ulna having osteometric parameters similar to the averages of our sample,
      and plate-to-bone fit was examined in two planes. RESULTS: The proximal ulna had
      an 8.48 degrees  (2.1 degrees -15.7 degrees ) mean varus angulation and an 8.49
      degrees  (1.70 degrees -14.10 degrees ) mean anterior angulation, located on
      average 8.19 cm (5.68-11.66 cm) and 8.63 cm (5.28-11.92 cm) distal to the bone's
      most proximal point, respectively. The mean olecranon angle was 110.34 degrees 
      (98.70 degrees -125.80 degrees ) and the olecranon length was 1.58 cm on average
      (1.20-2.12 cm). Only the plate having both varus and anterior angulation
      presented a good plate-to-bone fit in both planes. CONCLUSIONS: A "true"
      anatomical preshaped olecranon plate should have both varus and anterior
      angulation close to the average angulations of the normal ulna and located in a
      certain distance from its proximal edge. The olecranon part of the plate should
      primarily not exceed the olecranon length and secondarily be close to the average
      olecranon angle. We believe that such a plate may facilitate intraoperative
      restoration of the proximal ulna complex anatomy, when dealing with comminuted or
      Monteggia fractures, thus leading to better postoperative results.

PMID- 24671337
TI  - Comment on "anatomical variations in branching pattern of arcus aorta: 64-slice
      CTA appearance (Ergun et al. Surg Radiol Anat doi: 10.1007/s00276-012-1063-3)".

PMID- 24671339
TI  - Unstimulated and glucose-stimulated ghrelin in depressed patients and controls.
AB  - INTRODUCTION: The neuropeptide ghrelin stimulates hunger and weight gain. Ghrelin
      actions have been associated with depression in a number of preclinical and
      clinical studies, although some studies comparing basal peripheral ghrelin levels
      between depressed patients and controls found no differences between the groups.
      METHODS: Twenty patients with a melancholic depressive episode and 15 controls
      received a 75 g glucose load and ghrelin levels were measured at 0, 30, 60 and 90
      min after the beginning of the test. The patients were then either treated with
      mirtazapine (n=10) or venlafaxine (n=10) and underwent the same procedure
      (glucose load and ghrelin assessment) after four weeks of treatment. RESULTS:
      Basal ghrelin concentrations did not differ between patients and controls,
      although the ghrelin responses following the glucose load were lower in patients
      and differed significantly to the controls' responses. After treatment, the
      patients' ghrelin responses to the glucose load increased by trend and
      approximated those in the control group. CONCLUSION: Ghrelin is involved in
      appetite-regulating pathways during depression. For the first time we show that a
      functional test procedure using a standardised glucose load is more suitable than
      the assessment of basal peripheral ghrelin levels to detect differences between
      diagnostic groups.

PMID- 24671338
TI  - Amphetamine sensitisation and memory in healthy human volunteers: a functional
      magnetic resonance imaging study.
AB  - Amphetamine sensitisation (AS) is an established animal model of the
      hypersensitivity to psychostimulants seen in patients with schizophrenia. AS also
      models the dysregulation of mesolimbic dopamine signalling which has been
      implicated in the development of psychotic symptoms. Recent data suggest that the
      enhanced excitability of mesolimbic dopamine neurons in AS is driven by a
      hyperactivity of hippocampal (subiculum) neurons, consistent with a strong
      association between hippocampal dysfunction and schizophrenia. While AS can be
      modelled in human volunteers, its functional consequences on dopaminoceptive
      brain regions (i.e. striatum and hippocampus) remains unclear. Here we describe
      the effects of a sensitising dosage pattern of dextroamphetamine on the neural
      correlates of motor sequence learning in healthy volunteers, within a randomised,
      double-blind, parallel-groups design. Behaviourally, sensitisation was
      characterised by enhanced subjective responses to amphetamine but did not change
      performance (i.e. learning rate) during an explicit sequence learning task. In
      contrast, functional magnetic resonance imaging (fMRI) measurements showed that
      repeated intermittent amphetamine exposure was associated with increased blood
      oxygen-level dependent (BOLD) signal within the medial temporal lobe (MTL)
      (subiculum/entorhinal cortex) and midbrain, in the vicinity of the substantia
      nigra/ventral tegmental area (SN/VTA) during sequence encoding. Importantly, MTL
      hyperactivity correlated with the sensitisation of amphetamine-induced
      attentiveness. The MTL-midbrain hyperactivity reported here mirrors observations
      in sensitised rodents and is consistent with contemporary models of schizophrenia
      and behavioural sensitisation. These findings of meso-hippocampal hyperactivity
      during AS thus link pathophysiological concepts of dopamine dysregulation to
      cognitive models of psychosis. 

PMID- 24671340
TI  - Long-term efficacy, tolerability and safety of nalmefene as-needed in patients
      with alcohol dependence: A 1-year, randomised controlled study.
AB  - This study evaluated the long-term efficacy and safety of nalmefene treatment in
      reducing alcohol consumption. We randomised (1:3) 675 alcohol-dependent patients
      >= 18 years of age to 52 weeks of as-needed treatment with placebo or nalmefene
      18 mg/day: A total of 112 patients (68%) in the placebo group and 310 (62%) in
      the nalmefene group completed the study. At month 6, the co-primary outcome
      variables showed no statistically-significant differences between the treatment
      groups; but at month 13, nalmefene was more effective than placebo, both in the
      reduction of the number of heavy drinking days (HDDs) (- 1.6 days/month (95% CI -
      2.9; - 0.3); p = 0.017) and the reduction of total alcohol consumption (TAC) (-
      6.5 g/day last month (95% CI - 12.5; - 0.4); p = 0.036). In a subgroup analysis
      of patients with high/very high drinking risk levels at screening and at
      randomisation (the target population), there was a significant effect in favour
      of nalmefene on TAC at month 6, and on both HDD and TAC at month 13. Improvements
      in Clinical Global Impression and liver enzymes were greater with nalmefene,
      compared to placebo. Most adverse events were mild or moderate, and transient;
      adverse events, including those leading to dropout, were more common with
      nalmefene. This study provides evidence for the long-term safety and efficacy of
      nalmefene as-needed in alcohol-dependent patients whom continue to drink heavily,
      following a brief intervention. 

PMID- 24671341
TI  - Linking genetic counseling content to short-term outcomes in individuals at
      elevated breast cancer risk.
AB  - Few studies have linked actual genetic counseling content to short-term outcomes.
      Using the Self-regulation Model, the impact of cognitive and affective content in
      genetic counseling on short-term outcomes was studied in individuals at elevated
      risk of familial breast-ovarian cancer. Surveys assessed dependent variables:
      distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test;
      Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms
      of Cancer Inheritance; Frequency of Inherited Cancer) measured at pre- and post
      counseling. Proportion of participant cognitive and affective and counselor
      cognitive and affective content during sessions (using LIWC software) were
      predictors in regressions. Knowledge increased for 5 measures and decreased for
      Personal Behavior, Distress and Perceived Risk. Controlling for age and
      education, results were significant/marginally significant for three measures.
      More counselor content was associated with decreases in knowledge of Personal
      Behavior. More participant and less counselor affective content was associated
      with gains in Practitioner Knowledge. More counselor cognitive, and interaction
      of counselor cognitive and affective content, were associated with higher
      perceived risk. Genetic counselors dominate the content of counseling sessions.
      Therefore, their content is tied more closely to short term outcomes than
      participant content. A lack of patient communication in sessions may pose
      problems for understanding of complex concepts. 

PMID- 24671342
TI  - Genetic counselors' views and experiences with the clinical integration of genome
      sequencing.
AB  - In recent years, new sequencing technologies known as next generation sequencing
      (NGS) have provided scientists the ability to rapidly sequence all known coding
      as well as non-coding sequences in the human genome. As the two emerging
      approaches, whole exome (WES) and whole genome (WGS) sequencing, have started to
      be integrated in the clinical arena, we sought to survey health care
      professionals who are likely to be involved in the implementation process now
      and/or in the future (e.g., genetic counselors, geneticists and nurse
      practitioners). Two hundred twenty-one genetic counselors- one third of whom
      currently offer WES/WGS-participated in an anonymous online survey. The aims of
      the survey were first, to identify barriers to the implementation of WES/WGS, as
      perceived by survey participants; second, to provide the first systematic report
      of current practices regarding the integration of WES/WGS in clinic and/or
      research across the US and Canada and to illuminate the roles and challenges of
      genetic counselors participating in this process; and third to evaluate the
      impact of WES/WGS on patient care. Our results showed that genetic counseling
      practices with respect to WES/WGS are consistent with the criteria set forth in
      the ACMG 2012 policy statement, which highlights indications for testing,
      reporting, and pre/post test considerations. Our respondents described challenges
      related to offering WES/WGS, which included billing issues, the duration and
      content of the consent process, result interpretation and disclosure of
      incidental findings and variants of unknown significance. In addition,
      respondents indicated that specialty area (i.e., prenatal and cancer), lack of
      clinical utility of WES/WGS and concerns about interpretation of test results
      were factors that prevented them from offering this technology to patients.
      Finally, study participants identified the aspects of their professional training
      which have been most beneficial in aiding with the integration of WES/WGS into
      the clinical setting (molecular/clinical genetics, counseling and bioethics) and
      suggested that counseling aids (to assist them when explaining aspects of these
      tests to patients) and webinars focused on WES/WGS (for genetic counselors and
      other health care professionals) would be useful educational tools. Future
      research should permit us to further enhance our knowledge of pitfalls and
      benefits associated with the introduction of these powerful technologies in
      patient care and to further explore the roles and opportunities for genetic
      counselors in this rapidly evolving field. 

PMID- 24671343
TI  - Antenna effects in truxene-bridged BODIPY triarylzinc(II)porphyrin dyads:
      evidence for a dual Dexter-Forster mechanism.
AB  - The antenna process from an energy donor (BODIPY; 4',4'-difluoro-1',3',5',7'
      tetramethyl-4'-bora-3a',4a'-diaza-s-indacene) in its singlet state to two
      acceptors (two zinc(II) 5,15-p-tolyl-10-phenylporphyrin) bridged by a central
      truxene residue (5',5'',10',10'',15',15''-hexabutyltruxene), 5, has been analysed
      by means of comparison of the energy transfer rates with those of a structurally
      similar beta-substituted BODIPY-(zinc(II) 5,10,15-p-tolyl-porphyrin), 6, where no
      conjugation is present between the donor and the two acceptors using the Forster
      resonance energy transfer (FRET) approximation. It is estimated that the energy
      transfer in operates mostly via a Dexter mechanism (>99%), and the remaining
      proceeds via a Forster mechanism (<1%). This information is useful for the design
      of future molecular devices aimed at harvesting light.

PMID- 24671344
TI  - Synthesis, structure and reactivity of [o-(2,6
      diisopropylphenyliminomethinyl)phenyl]selenenyl selenocyanate (RSeSeCN) and
      related derivatives.
AB  - The synthesis and the first X-ray structural characterization of a selenenyl
      selenocyanate, [o-(2,6-diisopropylphenyliminomethinyl)phenyl]selenenyl
      selenocyanate (), with a stable Se-Se bond are described. The isolation of stable
      , both in the solid state and in solution, is facilitated by strong
      intramolecular SeN interaction. The compound , an example of unsymmetrical
      diselenide, did not exhibit any glutathione peroxidase-like activity. The
      reaction of with thiophenol afforded (3H-benzo[c][1,2]diselenol-3
      yl)(phenyl)sulfane. 

PMID- 24671345
TI  - [New from old : relevant factors for fracture healing in aging bone].
AB  - BACKGROUND: Fracture healing is a complex biological process with specific
      temporal expression patterns. During this process new bone tissue is formed,
      which is similar to the original bone in quality and structure. This occurs in
      four phases: inflammation, formation of a soft tissue callus, formation of a bony
      callus and remodelling of the bony callus. This needs the precise orchestration
      of each cell type involved. OBJECTIVES: This article presents details of the
      fracture healing phases and the relevant factors. During the aging process there
      is an increase of reactive oxygen species and a change in expression pattern of
      growth factors that have a negative effect on the fracture healing process.
      METHODS: A selective review of the literature was carried out in PubMed
      concerning the influence of aging on fracture healing. CONCLUSION: The healing
      process is regulated by systemic and local factors. An understanding of these
      processes and the changes during aging is necessary in order to improve the
      knowledge of delayed or lack of fracture healing during aging to decide when an
      intervention is needed.

PMID- 24671347
TI  - [Intra-articular fractures of the distal humerus : aspects of fracture treatment
      in geriatric patients].
AB  - BACKGROUND: In the context of osteoporotic fractures, injuries to the distal
      humerus are quite uncommon, meaning that each surgeon will have only limited
      experience. OBJECTIVE: This leads automatically to the question to what extent
      treatment recommendations can be transferred to the geriatric population.
      METHODS: Looking at the evidence-based literature, recommendations could be
      limited to three prospective studies. However, this only means that the remaining
      literature sources do not provide sufficient statistical power to be able to draw
      conclusions. RESULTS AND DISCUSSION: For the population of geriatric patients a
      thorough compilation of the contemporary literature is advisable. This review
      article on the currently available literature evaluates and individually
      discusses the relevant aspects of fracture treatment in order to develop
      recommendations for routine daily practice.

PMID- 24671346
TI  - [Fractures of the proximal humerus in the elderly : Osteosynthesis versus joint
      replacement].
AB  - BACKGROUND: Expected changes in population demographics will have significant
      implications for society and health care provision for the treatment of proximal
      humeral fractures in the elderly. OBJECTIVES: This article presents the incidence
      and clinical characteristics of geriatric fractures of the proximal humerus, a
      description of therapeutic options and treatment recommendations. METHODS: The
      published scientific data were reviewed and current opinion available to guide
      patient care are presented. RESULTS: The majority of fractures of the proximal
      humerus that require operative treatment are amenable to reconstruction. Primary
      arthroplasty is usually reserved for comminuted fractures with delayed
      presentation, head-splitting fractures or those in which the humeral head is
      devoid of soft tissue attachments. Secondary replacement may be required in cases
      of fixation failure and symptomatic avascular necrosis. CONCLUSION: Decision
      making is dependent on the fracture pattern as well as on patient and surgeon
      related factors.

PMID- 24671348
TI  - [Pediatric knee injuries].
AB  - Patella dislocations are the most common knee injuries causing hemarthrosis in
      children. Flake fractures represent the main complication of these injuries and
      require fixation. First time dislocations are treated conservatively. Recurrent
      dislocations are managed operatively. Precise analysis of the underlying
      dispositional and pathological factors is important to determine the appropriate
      operative procedure. To protect the growth plate, special techniques are
      required. Tibial spine fractures are bony avulsions of the anterior cruciate
      ligament (ACL). Management includes closed reduction in hyperextension and
      immobilization in a knee cast. Tibial spine fractures which cannot be reduced
      require operative treatment using either arthroscopic or open reduction and
      stabilization without injuring the growth plate. Intraligamentous ACL injuries
      are increasingly observed in children and adolescents. The risk of meniscus tears
      or chondral damage is high in these injuries. In case of persistent ACL
      instability, early reconstruction is recommended. Various techniques have been
      described; however, there is no consensus regarding the most favorable technique.
      The attending physician must be familiar with different ACL reconstruction
      techniques and with the anatomy of the growth plate. Meniscus tears require early
      suturing. Healing rates are good in children. 

PMID- 24671349
TI  - Laparoscopic transgastric endolumenal cystogastrostomy and pancreatic
      debridement.
AB  - BACKGROUND: Cystogastrostomy is commonly performed for internal drainage of
      pancreatic pseudocysts (PP) and concomitant debridement of walled-off pancreatic
      necrosis (WOPN). While an open approach to cystogastrostomy is well established,
      an optimal minimally invasive technique continues to evolve. This laparoscopic
      transgastric endolumenal cystogastrostomy presented here allows for a large
      cystogastrostomy with complete debridement of necrosis and internal drainage
      through a minimally invasive approach. METHODS: We performed a retrospective
      review of 22 patients with symptomatic PP/WOPN treated with attempted
      laparoscopic transgastric endolumenal cystogastrostomy (Lap-TEC) and pancreatic
      debridement. Short- and long-term outcomes were assessed. RESULTS: From November
      2006 to March 2013, a total of 22 Lap-TEC/pancreatic debridement procedures were
      attempted; 15 were completed laparoscopically. The median age of the cohort was
      49.5 +/- 12 years (range = 18-71), average body mass index = 29.1 kg/m(2), 77 %
      had an ASA score >= 3, and 10 were female. Gallstones were the most common
      etiology (50 %), and median time between initial presentation and surgery was 86
      days (range = 0-360). Median operative time and estimated blood loss were 213 min
      and 100 cc, respectively. Forty-one percent of the patients were admitted to the
      ICU postoperatively and the average length of stay was 14 days (range = 4-50).
      Median follow-up was 2 months (range = 0-62.5), with one patient having a
      procedure-related complication. No other reoperations, late complications, or
      mortalities occurred. All patients had resolution of their symptoms and fluid
      collections. CONCLUSION: This technique of internal drainage via Lap-TEC and
      pancreatic debridement has been successful in achieving primary drainage and
      relieving symptoms of PP/WOPN with no mortality and minimal morbidity.

PMID- 24671350
TI  - Modified laparoscopic intragastric surgery and endoscopic full-thickness
      resection for gastric stromal tumor originating from the muscularis propria.
AB  - BACKGROUND: This study aimed to evaluate the feasibility and security of the
      modified laparoscopic intragastric surgery (MLIGS) and the endoscopic full
      thickness resection (EFR) for the treatment of gastric stromal tumors (GSTs)
      originating from the muscularis propria. METHODS: The study population was 18
      patients with GSTs of the intraluminal muscularis propria layer. Eight were
      treated by MLIGS performed according to the following procedures: (1) gastroscopy
      was used to expose and confirm the location of the tumor; (2) a laparoscope light
      was placed in the cavity using the trocar at the navel, with the remaining two
      trocars penetrating both the abdominal and stomach walls; (3) the operation was
      performed in the gastric lumen using laparoscopic instruments with gastroscope
      monitoring, and the tumor was resected; (4) the tumor tissue was removed orally
      using a grasping forceps; (5) and the puncture holes and perforation in the
      stomach were sutured using titanium clips. The remaining 10 patients were treated
      by EFR, which involved (1) injection of normal saline into the submucosa and
      precutting of the mucosal and submucosal layer around the lesion, (2) a
      circumferential incision as deep as the muscularis propria around the lesion, (3)
      an incision into the serosal layer around the lesion, (4) completion of full
      thickness incision to the tumor, (5) closure of the gastric wall defect with
      clips. RESULTS: The GSTs all were resected completely. The two groups did not
      differ significantly in terms of tumor size, hospital stay, or abdominal pain
      time. But in the MLIGS group, the operation time and blood loss were
      significantly decreased compared with the EFR group. No postoperative
      complications occurred in the MLIGS group, whereas one peritoneal abscess
      occurred in the EFR group. The pathology of all the resected specimens showed
      GST. No case of implantation or metastasis was found. CONCLUSIONS: Both MLIGS and
      EFR are feasible and effective treatments for GSTs from the muscularis propria.
      Moreover, both are minimally invasive.

PMID- 24671351
TI  - Mckittrick-Wheelock syndrome: an often, overlooked complication of rectal
      adenomas.

PMID- 24671353
TI  - Determination of the latency effects on surgical performance and the acceptable
      latency levels in telesurgery using the dV-Trainer((r)) simulator.
AB  - BACKGROUND: The primary limitation of telesurgery is the communication latency.
      Accurate and detailed data are lacking to reveal the latency effects on surgical
      performance; furthermore, the maximum acceptable latency in telesurgery remains
      unclear. METHODS: Sixteen medical students performed an energy dissection
      exercise and a needle-driving exercise on the robotic simulator dV-Trainer((r)),
      and latencies varying between 0 and 1,000 ms with a 100-ms interval were randomly
      and blindly presented. Task completion time, instrument motion, and errors were
      automatically recorded. The difficulty, security, precision, and fluidity of
      manipulation were self-scored by subjects between 0 and 4 (0 the best, 2
      moderate, and 4 the worst). RESULTS: Task completion time, motion, and errors
      increased gradually as latency increased. An exponential regression was fit to
      the mean times and motions (R (2) > 0.98). Subjective scorings of the four items
      were similar. The mean scores were less than 1 at delays <=200 ms, then increased
      from 1 to 2 at 300-700 ms, and finally approached 3 at delays above. In both
      exercises, latencies <=300 ms were judged to be safe by all and 400-500 ms were
      accepted by 66-75 % of subjects. Less than 20 % of subjects accepted delays >=800
      ms. CONCLUSIONS: The surgical performance deteriorates in an exponential way as
      the latency increases. The delay impact on instrument manipulation is mild at 0
      200 ms, then increases from small to large at 300-700 ms, and finally becomes
      very large at 800-1,000 ms. Latencies <=200 ms are ideal for telesurgery; 300 ms
      is also suitable; 400-500 ms may be acceptable but are already tiring; and 600
      700 ms are difficult to deal with and only acceptable for low risk and simple
      procedures. Surgery is quite difficult at 800-1,000 ms, telementoring would be a
      better choice in this case.

PMID- 24671352
TI  - Effects of sleep hours and fatigue on performance in laparoscopic surgery
      simulators.
AB  - BACKGROUND: Studies on a virtual reality simulator have demonstrated that sleep
      deprived residents make more errors. Work-hour restrictions were implemented,
      among other reasons, to ensure enough sleep time for residents. The objective of
      this study was to assess the effects of sleep time, perceived fatigue, and
      experience on surgical performance. We hypothesized that performance would
      decrease with less sleep and fatigue, and that experienced surgeons would perform
      better than less experienced surgeons despite sleep deprivation and fatigue.
      METHODS: Twenty-two surgical residents and attendings performed a peg transfer
      task on two simulators: the Fundamentals of Laparoscopic Skills (FLS) trainer and
      the Virtual Basic Laparoscopic Surgical Trainer (VBLaST(c)), a virtual version of
      the FLS. Participants also completed questionnaires to assess their fatigue level
      and recent sleep hours. Each subject performed ten trials on each simulator in a
      counterbalanced order. Performance was measured using the FLS normalized scores
      and analyzed using a multiple regression model. RESULTS: The multiple regression
      analysis showed that sleep hours and perceived fatigue were not covariates. No
      correlation was found between experience level and sleep hours or fatigue. Sleep
      hours and fatigue did not appear to affect performance. Expertise level was the
      only significant determinant of performance in both FLS and VBLaST(c).
      CONCLUSIONS: Restricting resident work hours was expected to result in less
      fatigue and better clinical performance. In our study, peg transfer task
      performance was not affected by sleep hours. Experience level was a significant
      indicator of performance. Further examination of the complex relationship between
      sleep hour, fatigue, and clinical performance is needed to support the practice
      of work-hour restriction for surgical residents.

PMID- 24671354
TI  - Intuitive user interfaces increase efficiency in endoscope tip control.
AB  - BACKGROUND: Flexible endoscopes are increasingly used to perform advanced
      intraluminal and transluminal interventions. These complex interventions demand
      accurate and efficient control, however, current endoscopes lack intuitiveness
      and ergonomic control of the endoscope tip. Alternative handheld controllers can
      improve intuitiveness and ergonomics, though previous studies are inconclusive
      concerning their effect on the efficiency of endoscope manipulation. The aim of
      this study is to determine the efficiency of a robotic system with intuitive user
      interface in controlling the tip of the flexible endoscope. METHODS: We compared
      the efficiency of time and tip trajectory when steering the endoscope tip using
      the conventional steering wheels and a robotic platform with three different user
      interfaces: a touchpad in combination with a position control algorithm, a
      joystick combined with linear rate control, and a joystick combined with non
      linear rate control. Fourteen participants, without a medical background, used
      all four interfaces. They performed both large navigational and fine targeting
      tasks in a simulated environment which allowed objective cross-subject
      comparison. Afterward, the participants were asked to select their preferred
      steering method. RESULTS: Participants were significantly faster in steering the
      endoscope tip when using robotic steering compared to using the conventional
      steering method. Between the robotic interfaces, using the touchpad was
      significantly faster compared to the joystick with linear rate control. Use of
      the joystick with non-linear rate control led to a shorter tip trajectory
      compared to the touchpad. The majority of participants preferred the joystick
      with non-linear rate control over the other steering methods. CONCLUSIONS: This
      work shows that intuitive user interfaces can improve the efficiency of endoscope
      tip steering.

PMID- 24671355
TI  - Proton transfer reactions of 4'-chloro substituted 3-hydroxyflavone in solvents
      and aqueous micelle solutions.
AB  - Flavonol 4'-chloro,3-hydroxyflavone (Cl-3HF) has been investigated in solvents of
      varying polarity and hydrogen-bonding capacity as well as in aqueous micelle
      solutions. Quantum chemical calculations indicate that although the Cl-atom at
      the 4'-position of the 2-phenyl ring weakly perturbs the electron distribution of
      the parent 3-hydroxyflavone, the nuclear framework remains largely intact, and
      excited state intra-molecular proton-transfer (ESIPT) is feasible. The ESIPT
      process in both polar solvents and micelles was found to be fast and
      irreversible, with remarkably long time-constants of several tens of picoseconds.
      This dramatic inhibition of the ESIPT rate (which is intrinsically a sub
      picosecond event) could be rationalized in terms of the emergence of complexes
      between the solvent and the enol form of Cl-3HF, whose dynamics is coupled to the
      relatively slow dynamics of inter-molecular hydrogen bonds. In the micelle
      solutions, spectroscopic data establish that the guest Cl-3HF molecules localized
      almost exclusively at the polar exterior shell, where they experienced a nearly
      uniform local environment similar to that in moderately polar solvents. Thus, the
      Cl-3HF molecules tend to avoid the non-polar core of the micelles, in spite of
      being strongly hydrophobic themselves. This apparently unusual observation is
      explained by the formation of inter-molecularly hydrogen-bonded complexes between
      the guest Cl-3HF and the water molecules tethered to the polar shells of the
      micelles. 

PMID- 24671356
TI  - Fatal breast cancer risk in relation to use of unopposed estrogen and combined
      hormone therapy.
AB  - Use of combined hormone therapy (CHT) is associated with increased breast cancer
      incidence, but it is unclear whether this translates into increased breast cancer
      mortality. To address this question, we conducted a population-based nested case
      control study in Saskatchewan, Canada, where a population-based prescription drug
      database has existed since 1975. We evaluated fatal breast cancer risk in
      relation to recency and duration of use of CHT and unopposed estrogen hormone
      therapy (EHT). A total of 1,288 cases and 12,535 controls were included in the
      analyses. Exclusive use of EHT was not associated with fatal breast cancer risk,
      either overall or within categories of recency or duration [odds ratio (OR) for
      current vs. never use = 1.1; 95 % confidence interval (CI) 0.8-1.3]. Use of CHT
      (includes women who had also used EHT) was also not associated with fatal breast
      cancer risk (OR for current vs. never use = 0.9; 95 % CI 0.7-1.3), except for a
      suggestion of an increased risk with current long-term use. Consistent with prior
      studies, we observed no increased risk of fatal breast cancer associated with use
      of EHT. To date only a few studies have evaluated fatal breast cancer risk in
      relation to use of CHT, and collectively the results are inconsistent. 

PMID- 24671357
TI  - Expression of organic anion-transporting polypeptide 1A2 and organic cation
      transporter 6 as a predictor of pathologic response to neoadjuvant chemotherapy
      in triple negative breast cancer.
AB  - Organic anion-transporting polypeptide 1A2 (OATP1A2) and organic cation
      transporter 6 (OCT6) are involved in the uptake of taxanes and anthracyclines,
      respectively. The aim of this study was to evaluate expression levels of OATP1A2
      and OCT6 as a predictor of response to neoadjuvant chemotherapy (NAC) in breast
      cancer. A total of 124 patients who received anthracycline/taxane-based NAC were
      included. Expression levels of OATP1A2 and OCT6 were immunohistochemically
      assessed in core needle biopsies obtained prior to NAC. A pathologic good
      response (pGR) and a pathologic complete response (pCR) were achieved in 24 and
      10 % of patients, respectively. In univariate analysis of the entire cohort,
      negative hormone receptor (HR) status (pGR and pCR, P < 0.001), high Ki-67 level
      (pGR, P = 0.03; pCR, P = 0.02), triple negative (TN) subtype (pGR, P = 0.001;
      pCR, P < 0.001), and high OCT6 (pGR, P = 0.003) were associated with the
      response. In combined analysis, high OATP1A2/high OCT6 level was also a
      significant factor for pGR (P = 0.001) and pCR (P = 0.001). Two separate
      multivariate analyses showed that HR status, TN subtype and combined high
      OATP1A2/high OCT6 level were significant independent predictors. When TN and non
      TN tumors were assessed separately in univariate analysis, high Ki-67 level (P =
      0.04) were associated with pGR and combined high OATP1A2/high OCT6 level was
      associated with both pGR (P = 0.005) and pCR (P = 0.03) in the TN group.
      Multivariate analysis identified the combined high OATP1A2/high OCT6 level as the
      sole independent predictor of pGR. In the non-TN group, negative HR status (P =
      0.03) and positive HER2 status (P = 0.005) were associated with pGR, but HER2
      status was the sole independent predictor of pGR. These results suggest that
      response-associated predictors may differ between the TN and non-TN tumors.
      Combined high OATP1A2/high OCT6 may be a potential predictor of response to
      anthracycline/taxane-based chemotherapy in breast cancer, especially in TN
      tumors.

PMID- 24671358
TI  - What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a
      meta-analysis.
AB  - To evaluate the incidence of chemotherapy-induced amenorrhea (CIA) and its
      therapeutic impact in premenopausal breast cancer patients. A systematic search
      was performed to identify clinical studies that compared the incidence of CIA
      with different chemotherapy regimens and oncological outcomes with and without
      CIA. The fixed-effects and random-effects models were used to assess the pooled
      estimates. Heterogeneity and sensitivity analyses were performed to explore
      heterogeneity among studies and to assess the effects of study quality. A total
      of 15,916 premenopausal breast cancer patients from 46 studies were included. The
      cyclophosphamide-based regimens, taxane-based regimens, and
      anthracycline/epirubicin-based regimens all increased the incidence of CIA with
      pooled odds ratios of 2.25 (95 % CI 1.26-4.03, P = 0.006), 1.26 (95 % CI 1.11
      1.43, P = 0.0003) and 1.39 (95 % CI 1.15-1.70, P = 0.0008), respectively. The
      three-drug combination regimens of cyclophosphamide,anthracycline/epirubicin, and
      taxanes (CAT/CET) caused the highest rate of CIA compared with the other three
      drug combinations (OR 1.41, 95 % CI 1.16-1.73, P = 0.0008). Tamoxifen therapy was
      also correlated with a higher incidence of CIA, with an OR of 1.48. Patients with
      CIA were found to exhibit better disease-free survival (DFS) and overall survival
      (OS) compared with patients without CIA. With respect to molecular subtype, this
      DFS advantage remained significant in hormone-sensitive patients (HR 0.61, 95 %
      CI 0.52-0.72, P < 0.00001). The current meta-analysis has demonstrated that
      anthracycline/epirubicin, taxanes, cyclophosphamide, and tamoxifen all
      contributed to elevated rates of CIA, and CIA was not merely a side effect of
      chemotherapy but was a better prognostic marker, particularly for ER-positive
      premenopausal early-stage breast cancer patients. However, this topic merits
      further randomized control studies to detect the associations between CIA and
      patient prognosis after adjusting for age, ER status, and other influential
      factors.

PMID- 24671360
TI  - Vertical junction photodetectors based on reduced graphene oxide/silicon Schottky
      diodes.
AB  - Reduced graphene oxide (RGO) has been employed as an electrode for a series of
      vertically structured photodetectors. Compared with mechanically exfoliated or
      chemical vapor deposited graphene, RGO possesses more oxygen containing groups
      and defects, which are proved to be favorable to enhance the performance of
      photodetectors. As a matter of fact, RGO with different reduction levels can be
      readily obtained by varying the annealing temperature. The synthesis procedures
      for the RGO material are suitable for large scale production and its performance
      can be effectively improved by functionalization or element doping. For RGO-based
      devices, the Schottky junction properties and photoelectric conversion have been
      investigated, primarily by analyzing their current-voltage characteristics.
      Subsequently, the ON/OFF ratio, responsivity and detectivity of the
      photodetectors were closely examined, proving that the RGO material could be
      effectively utilized as the electrode material; also, their relationship with the
      RGO reduction levels has also been explored. By analyzing the response/recovery
      speed of the RGO-based photodetectors, we have studied the effects of oxygen
      containing functional groups and crystalline defects on the photoelectric
      conversion. 

PMID- 24671359
TI  - Diagnostic performance of breast-specific gamma imaging in the assessment of
      residual tumor after neoadjuvant chemotherapy in breast cancer patients.
AB  - To evaluate the diagnostic performance of breast-specific gamma imaging (BSGI) in
      the assessment of residual tumor after neoadjuvant chemotherapy (NAC) in breast
      cancer patients, female breast cancer patients who underwent NAC, preoperative
      (99m)Tc-sestamibi BSGI, and subsequent definitive breast surgery were enrolled
      retrospectively. The accuracy of BSGI in the assessment of residual tumor
      presence and residual tumor size was evaluated and compared to that of magnetic
      resonance imaging (MRI) using pathology results as the gold standard. The
      sensitivity and specificity of BSGI for residual tumor detection in 122 enrolled
      patients were 74.0 and 72.2 %, respectively, and were comparable to those of MRI
      (81.7 and 72.2 %; P > 0.100). The residual tumor size was significantly
      underestimated by BSGI in the luminal subtype (P = 0.008) and by MRI in the
      luminal (P < 0.001) and HER2 subtypes (P = 0.032), with a significantly lesser
      degree of underestimation by BSGI than MRI in both subtypes. In the triple
      negative subtype, both BSGI and MRI generated accurate tumor size measurements.
      The residual cellularity of triple-negative tumors was significantly higher than
      that of the non-triple-negative tumors (P = 0.017). The diagnostic performance of
      BSGI in the assessment of residual tumor is comparable to that of MRI in breast
      cancer patients. The assessment of residual tumor extent by BSGI depends on the
      molecular subtype, but BSGI may be more accurate than MRI. Underestimation of
      tumor size in the luminal and/or HER2 subtypes by BSGI and MRI may be due to low
      residual cellularity.

PMID- 24671361
TI  - Impact of electronic reminders on venous thromboprophylaxis after admissions and
      transfers.
AB  - OBJECTIVE: Clinical decision support has the potential to improve prevention of
      venous thromboembolism (VTE). The purpose of this prospective study was to
      analyze the effect of electronic reminders on thromboprophylaxis rates in wards
      to which patients were admitted and transferred. The latter was of particular
      interest since patient handoffs are considered to be critical safety issues.
      METHODS: The trial involved two study periods in the six departments of a
      university hospital, three of which were randomly assigned to the intervention
      group displaying reminders during the second period. At 6 h after admission or
      transfer, the algorithm checked for prophylaxis orders within 0-30 h of the
      patient's arrival, increasing the specificity of the displayed reminders.
      RESULTS: The significant impact of the reminders could be seen by prophylaxis
      orders placed 6-24 h after admission (increasing from 8.6% (223/2579) to 12%
      (307/2555); p<0.0001) and transfer (increasing from 2.4% (39/1616) to 3.7%
      (63/1682); p=0.034). In admission wards, the rate of thromboprophylaxis increased
      from 62.4% to 67.7% (p<0.0001), and in transfer wards it increased from 80.2% to
      84.3% (p=0.0022). Overall, the rate of prophylaxis significantly increased in the
      intervention group from 69.2% to 74.3% (p<0.0001). No significant changes were
      observed in the control group. Postponing prophylaxis checks to 6 h after
      admissions and transfers reduced the number of reminders by 62% and thereby
      minimized the risk of alert fatigue. CONCLUSIONS: The reminders improved
      awareness of VTE prevention in both admission and transfer wards. This approach
      may contribute to better quality of care and safer patient handoffs.

PMID- 24671362
TI  - EPR dosimetry intercomparison using smart phone touch screen glass.
AB  - This paper presents the results of an interlaboratory comparison of retrospective
      dosimetry using the electron paramagnetic resonance method. The test material
      used in this exercise was glass coming from the touch screens of smart phones
      that might be used as fortuitous dosimeters in a large-scale radiological
      incident. There were 13 participants to whom samples were dispatched, and 11
      laboratories reported results. The participants received five calibration samples
      (0, 0.8, 2, 4, and 10 Gy) and four blindly irradiated samples (0, 0.9, 1.3, and
      3.3 Gy). Participants were divided into two groups: for group A (formed by three
      participants), samples came from a homogeneous batch of glass and were stored in
      similar setting; for group B (formed by eight participants), samples came from
      different smart phones and stored in different settings of light and temperature.
      The calibration curves determined by the participants of group A had a small
      error and a critical level in the 0.37-0.40-Gy dose range, whereas the curves
      determined by the participants of group B were more scattered and led to a
      critical level in the 1.3-3.2-Gy dose range for six participants out of eight.
      Group A were able to assess the dose within 20 % for the lowest doses (<1.5 Gy)
      and within 5 % for the highest doses. For group B, only the highest blind dose
      could be evaluated in a reliable way because of the high critical values
      involved. The results from group A are encouraging, whereas the results from
      group B suggest that the influence of environmental conditions and the
      intervariability of samples coming from different smart phones need to be further
      investigated. An alongside conclusion is that the protocol was easily transferred
      to participants making a network of laboratories in case of a mass casualty event
      potentially feasible.

PMID- 24671363
TI  - Enhanced intracellular targeting of tumor-specific antigens: you can lead a horse
      to water, but....

PMID- 24671364
TI  - Relapse assessment following allogeneic SCT in patients with MDS and AML.
AB  - Options to pre-emptively treat impending relapse of myelodysplastic syndromes
      (MDS) and acute myeloid leukaemia (AML) after allogeneic haematopoietic stem cell
      transplantation (allo-SCT) continuously increase. In recent years, the spectrum
      of diagnostic methods and parameters to perform post-transplant monitoring in
      patients with AML and MDS has grown. Cytomorphology, histomorphology, and
      chimaerism analysis are the mainstay in any panel of post-transplant monitoring.
      This may be individually combined with multiparameter flow cytometry (MFC) for
      the detection of residual cells with a leukaemia phenotype and quantitative real
      time polymerase chain reaction (RQ-PCR) to assess gene expression, e.g., of WT1
      or the residual mutation load (e.g., in case of an NPM1 mutation). Data
      evaluating the aforementioned methods alone or in combination are discussed in
      this review with particular emphasis on data pointing towards their suitability
      to steer pre-emptive post-transplant interventions such as immunotherapy,
      chemotherapy or therapy with demethylating agents. 

PMID- 24671366
TI  - Oral cancer awareness among community-dwelling senior citizens in Illinois.
AB  - The study assessed participant awareness of oral cancer (OC), risk factors, signs
      and symptoms, and history of an OC screening exam and whether a relationship
      exists between these factors and the participant's age, level of education,
      socioeconomic status (SES), ethnicity, and gender. It was a descriptive survey
      research with a non-randomized sample. Participants were a convenience sample of
      seniors participating in a congregate dining program of the DuPage County Senior
      Citizens Council. Data was collected through a written, self-administered survey.
      Sixty-two surveys were completed, with an overall response rate of 66%. A
      statistically significant relationship was found between the level of education
      and awareness of OC risk factors (r = 0.26; P = 0.04). An inverse relationship
      was found between the level of education and the level of OC awareness questions,
      "have you ever heard about OC?" (r = -0.37; P = 0.004), and "how much do you know
      about OC?" (r = 0.35; P = 0.008). A trend toward significance was noted for the
      level of education and awareness of OC signs and symptoms (r = 0.24; P = 0.06).
      The levels of OC awareness in the seniors were lower than the general population.
      Seniors in the lower SES strata and who have low education levels are of
      particular concern, and it is important to conduct further studies tailored
      towards populations with these combined factors. Additional research is needed to
      determine how to best communicate OC awareness and implement programs
      specifically for this high-risk group.

PMID- 24671365
TI  - Chromosome 13 deletion and hypodiploidy on conventional cytogenetics are robust
      prognostic factors in Korean multiple myeloma patients: web-based multicenter
      registry study.
AB  - This study was designed to evaluate the prevalence of chromosomal abnormalities
      and to identify the specific abnormalities associated with poor prognosis. A
      total of 2,474 patients whose conventional cytogenetics were available at the
      time of diagnosis were evaluated via a nationwide registry. Normal metaphase
      cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with
      chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy,
      197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with
      near-tetraploidy. Deletion 13 (Delta13) in metaphase was observed in 167 patients
      (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients
      (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were
      positive for t(4;14) and del(17p), respectively. With a median follow-up duration
      of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence
      interval, 46.5-55.9 months). In univariate analysis, the following four
      chromosomal abnormalities were significantly associated with a poor survival
      outcome: Delta13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the
      subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were
      excluded due to a relatively low number of patients, Delta13 and hypodiploid
      status were independently associated with a poor survival outcome after adjusting
      for important clinical factors, including age, sex, performance, beta2
      microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional
      metaphase cytogenetics, we confirmed that both Delta13 and hypodiploid status
      were robust poor prognostic factors. The metaphase karyotyping should remain the
      primary cytogenetic tool and an essential investigation for risk stratification
      in newly diagnosed multiple myeloma patients.

PMID- 24671367
TI  - Calorie intake, sugar-sweetened beverage consumption, and obesity among New York
      City adults: findings from a 2013 population study using dietary recalls.
AB  - Obesity and overweight-obesity have contributed to increases in early mortality
      and noncommunicable disease incidence. The consumption of sugar-sweetened
      beverages (SSBs) is linked to obesity, weight gain, and metabolic syndrome. To
      further explore this relationship in a large urban environment, we assessed
      disparities in calorie intake between SSB and non-SSB consumers and determine the
      association between varying SSB consumption, obesity, and overweight-obesity
      using data from a 2013 representative dietary survey conducted in New York City.
      Results show that adult SSB drinkers consume 193 kcal/day from SSBs,
      approximately 10% of daily caloric needs. Compared to non-SSB drinkers, those who
      consume SSBs have a 572 kcal greater daily intake. Total calorie differences are
      due to greater SSB calorie and food calorie consumption. Among SSB consumers,
      each 10-oz increase in SSB consumption is associated with a greater likelihood of
      obesity (OR 1.62, 95% CI 1.05, 2.05) and overweight-obesity (OR 2.23, 95% CI
      1.31, 3.80). Additionally, each 10-kcal SSB increase is related to obesity (OR
      1.04, 95% CI 1.01, 1.08) and overweight-obesity (OR 1.07, 95% CI 1.02, 1.11).

PMID- 24671368
TI  - Initial challenges in the career of ophthalmologists.

PMID- 24671369
TI  - Hypopnea: 'rule of thumb' or ruler and plumb?

PMID- 24671370
TI  - Calcium supplementation: is protecting against osteoporosis counter to protecting
      against cardiovascular disease?
AB  - Calcium is the dominant mineral in bone and is a shortfall nutrient in the diet.
      For those consuming inadequate dietary calcium, calcium supplements have been a
      standard strategy for prevention of osteoporosis. Recently, calcium
      supplementation has been linked to both increased and decreased cardiovascular
      disease risk creating considerable uncertainty. Moreover, recent reports have
      shed uncertainty over the effectiveness of calcium supplements to reduce risk of
      fracture. The evidence for calcium supplementation effects to both reduce risk of
      fracture and increase coronary heart disease and mortality are reviewed. Although
      the importance of good calcium nutrition is well known, determining the advantage
      of calcium supplementation to either bone or heart health has been hampered by
      poor subject compliance and study design flaws. At present, the current
      Recommended Dietary Allowances for calcium still appear to be a good target with
      potential risks for chronic disease if intakes fall too short or greatly exceed
      these recommendations. 

PMID- 24671372
TI  - A lanthanide based sensor for the time-gated detection of hydrogen sulfide.
AB  - A kinetically stable Eu(III) complex for the detection of sulfide in water is
      reported. The probe shows excellent selectivity and fast reaction time. Its long
      lived luminescence makes this the first probe for the time-gated detection of
      sulfide in complex biological samples.

PMID- 24671371
TI  - The effects of flavonoids on bone.
AB  - Osteoporosis and fragility fractures are a growing problem for our aging
      population with around 1 in 2 women and 1 in 5 men suffering from an osteoporotic
      fracture during their lifetime. Although there are established factors that can
      reduce the risk of fracture such as maintaining physical activity, ceasing
      smoking, and adequate vitamin D status, and intakes of calcium; dietary
      mechanisms are less well established. The relevance of the flavonoid group of
      bioactive compounds found in fruits and vegetables has been less investigated.
      Two human epidemiologic studies in women found positive associations between
      total dietary flavonoid intake and bone mineral density. Flavonoids may protect
      against bone loss by upregulating signaling pathways that promote osteoblast
      function, by reducing the effects of oxidative stress or chronic low-grade
      inflammation. The limitations of the existing research are explored in the
      manuscript and it is concluded that further research is needed, in this promising
      area. 

PMID- 24671373
TI  - High-altitude cerebral oedema mimicking stroke.
AB  - High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen
      by rural physicians practising in high-altitude areas. HACO presents clinically
      with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma.
      Early identification is important as delay in diagnosis can be fatal. We present
      two cases of HACO presenting with focal deficits mimicking stroke. The first
      patient presented with left-sided hemiplegia associated with the rapid
      deterioration in the sensorium. Neuroimaging revealed features suggestive of
      vasogenic oedema. The second patient presented with monoplegia of the lower limb.
      Neuroimaging revealed perfusion deficit in anterior cerebral artery territory.
      Both patients were managed with dexamethasone and they improved dramatically.
      Clinical picture and neuroimaging closely resembled acute ischaemic stroke in
      both cases. Thrombolysis in these patients would have been disastrous. Recent
      travel to high altitude, young age, absence of atherosclerotic risk factors and
      features of raised ICP concomitantly directed the diagnosis to HACO. 

PMID- 24671375
TI  - Dinuclear NHC-palladium complexes containing phosphine spacers: synthesis, X-ray
      structures and their catalytic activities towards the Hiyama coupling reaction.
AB  - Six dinuclear N-heterocyclic carbene (NHC) palladium complexes, [PdCl2(IMes)]2(MU
      dppe) (1), [PdCl2(IPr)]2(MU-dppe) (2), [PdCl2(IMes)]2(MU-dppb) (3),
      [PdCl2(IPr)]2(MU-dppb) (4), [PdCl2(IMes)]2(MU-dpph) (5), and [PdCl2(IPr)]2(MU
      dpph) (6) [IMes = N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene; IPr = N,N'
      bis-(2,6-di(iso-propyl)phenyl)imidazol-2-ylidene; dppe = 1,2
      bis(diphenylphosphino)ethane, dppb = 1,4-bis(diphenylphosphino)butane; and dpph =
      1,6-bis(diphenylphosphino)hexane], have been synthesized through bridge-cleavage
      reactions of chloro-bridged dimeric compounds, [Pd(MU-Cl)(Cl)(NHC)]2, with the
      corresponding diphosphine ligands. The obtained compounds were fully
      characterized by (1)H NMR, (13)C NMR and (31)P NMR spectroscopy, FT-IR, elemental
      analysis and single-crystal X-ray crystallography. Moreover, further explorations
      of the catalytic potential of the dinuclear carbene palladium complexes as
      catalysts for the Pd-catalyzed transformations have been performed under
      microwave irradiation conditions, and the complexes exhibited moderate to good
      catalytic activity in the Hiyama coupling reaction of trimethoxyphenylsilane with
      aryl chlorides. 

PMID- 24671374
TI  - Comparison of the performance of the different classification criteria for
      primary Sjogren's syndrome: a prospective cohort study.
AB  - The objective of the study is to compare the longitudinal performance of
      different classification criteria for primary Sjogren's syndrome (SS) in a cohort
      of patients previously diagnosed with primary SS. In each patient, we repeated
      diagnostic tests as required by the Copenhagen, European, Californian, and
      American-European Consensus Group (AECG) or the new American College of
      Rheumatology (ACR) classification criteria. Sixty-three out of 90 eligible
      patients (70 %) consented to participate. During the follow-up (mean (standard
      deviation, SD) 7.6 years (0.5)), we observed evolution from primary SS to SS with
      another systemic autoimmune disease (SAD) in 9/63 (14 %) patients, on average
      after 4.0 years (SD 0.9). The evolution from primary SS to SS-SADs was
      significantly more common if the diagnosis of primary SS was initially made using
      AECG (17 %, p = 0.008) or ACR (16 %, p = 0.016) criteria. In the 34 patients who
      underwent a full diagnostic reassessment, the diagnosis retention rate was
      statistically significant for all the criteria, except the European criteria. At
      reassessment, 3/32 (9 %) patients initially diagnosed as having primary SS using
      the European criteria could not be classified as having primary SS by any of the
      criteria. The differences in classification when using the AECG and the new ACR
      criteria were not statistically significant. The longitudinal diagnosis retention
      rate was highest for the Californian and AECG criteria. Regardless of the
      classification criteria, some patients eventually develop another SAD. 

PMID- 24671376
TI  - Antitussive drugs--past, present, and future.
AB  - Cough remains a serious unmet clinical problem, both as a symptom of a range of
      other conditions such as asthma, chronic obstructive pulmonary disease,
      gastroesophageal reflux, and as a problem in its own right in patients with
      chronic cough of unknown origin. This article reviews our current understanding
      of the pathogenesis of cough and the hypertussive state characterizing a number
      of diseases as well as reviewing the evidence for the different classes of
      antitussive drug currently in clinical use. For completeness, the review also
      discusses a number of major drug classes often clinically used to treat cough but
      that are not generally classified as antitussive drugs. We also reviewed a number
      of drug classes in various stages of development as antitussive drugs. Perhaps
      surprising for drugs used to treat such a common symptom, there is a paucity of
      well-controlled clinical studies documenting evidence for the use of many of the
      drug classes in use today, particularly those available over the counter.
      Nonetheless, there has been a considerable increase in our understanding of the
      cough reflex over the last decade that has led to a number of promising new
      targets for antitussive drugs being identified and thus giving some hope of new
      drugs being available in the not too distant future for the treatment of this
      often debilitating symptom. 

PMID- 24671378
TI  - A new pyrene based highly sensitive fluorescence probe for copper(II) and
      fluoride with living cell application.
AB  - A new pyrene based fluorescence probe has been synthesized for fluorogenic
      detection of Cu(2+) in acetonitrile-aqueous media (7 : 3 CH3CN-HEPES buffer, v/v,
      at pH 7.5) with bioimaging in both prokaryotic (Candida albicans cells) and
      eukaryotic (Tecoma stans pollen cells) living cells. The anion recognition
      properties of the sensor have also been studied in acetonitrile by fluorescence
      methods which show remarkable sensitivity toward fluoride over other anions
      examined. 

PMID- 24671379
TI  - Retraction Note: diagnostic accuracy of 320-row computed tomography as compared
      with invasive coronary angiography in unselected, consecutive patients with
      suspected coronary artery disease.

PMID- 24671380
TI  - Conformational propensities and dynamics of a betagamma-crystallin, an
      intrinsically disordered protein.
AB  - The three-dimensional folded structure of a protein has been considered essential
      for its function. However, recently many proteins have been identified to
      function without having a definite structure and they have been classified as
      intrinsically disordered proteins (IDPs). Recently, we have identified a
      betagamma-crystallin domain in the genome of a marine bacterium called Hahella
      chejuensis on the basis of known sequence signatures. This protein, called
      Hahellin, was characterized by NMR spectroscopy as an IDP, which upon Ca(2+)
      binding was shown to undergo a large conformational transformation and acquires a
      typical betagamma-crystallin fold. In this paper, we have characterized this IDP
      by a combined use of NMR and Replica Exchange Molecular Dynamics simulation and
      found it to be in a highly dynamic, inter-converting population having a molten
      globular state with the C-terminal Greek key motif relatively more flexible as
      compared to its N-terminal counterpart. Network analysis and clustering on the
      observed conformational ensemble showed a heterogeneous mixture of eleven
      distinct clusters, classified into near-native and far-native populations, which
      are not in equilibrium. Several conformational clusters display an increased
      propensity for helical conformation(s) and a decreased beta-strand propensity,
      which is consistent with the NMR observations made on this protein. The
      negatively charged Ca(2+)-coordinating residues form parts of the highly flexible
      polypeptide stretches, and thus act as seeds for the origin of different
      conformational clusters observed. This study thus helps us to understand the
      relationship between the role of conformational dynamics and the structural
      propensities of the intrinsically disordered state of apo-Hahellin. 

PMID- 24671382
TI  - Abstracts of the 16th ESSKA Congress, 14-17 May 2014, Amsterdam, The Netherlands.

PMID- 24671384
TI  - Change of gait in patients with lateral osteoarthritis of the knee after mobile
      bearing unicompartmental knee arthroplasty.
AB  - PURPOSE: Patients with lateral osteoarthritis of the knee suffer not only from
      pain but also impaired gait and limited mobility. Common treatment options are
      total knee replacement and lateral unicompartmental knee arthroplasty (UKA). The
      domed lateral mobile-bearing Oxford Uni is a new treatment option for patients
      with isolated osteoarthritis of the lateral compartment of the knee joint. We
      used instrumented gait analysis and clinical scores to study patients before and
      after lateral UKA. METHODS: Nineteen patients suffering from lateral
      osteoarthritis underwent implantation of a mobile-bearing lateral UKA. They were
      examined in a gait analysis before the operation and after an average follow-up
      time of 7 months. Gait analysis was performed on a treadmill with six infrared
      cameras to identify gait characteristics (e.g. velocity, stride time, stride
      length, knee abduction or hip adduction). RESULTS: Mean velocity changed from
      0.58 to 0.73 m/s. Significant advancements were also found in knee abduction and
      hip adduction. Time and length of strides improved significantly as well as the
      clinical scores American Knee Society Score, Oxford-12, FFb-H-OA and Devane
      Score. CONCLUSION: Patients with lateral osteoarthritis of the knee showed an
      impaired gait with an increased knee abduction and hip adduction angle.
      Implantation of a lateral mobile UKA can restore normal axis of the leg and
      improve gait and function of the knee. Instrumented gait analysis is a suitable
      measuring instrument to quantify and qualify the post-operative change of gait.
      LEVEL OF EVIDENCE: II.

PMID- 24671385
TI  - Prevalence and consequences of delayed diagnosis of anterior cruciate ligament
      ruptures.
AB  - PURPOSE: Rupture of the anterior cruciate ligament (ACL) is a common injury,
      often presenting with a typical injury pattern. Historically, the literature
      indicates that the accuracy of diagnosis of ACL ruptures is poor at the initial
      medical consultation. The aims of this study were to determine: the mechanism of
      injury; changes in accuracy of diagnosis of ACL ruptures at initial presentation
      over the last decade; and the effect of subsequent delay in diagnosis and
      definitive treatment. METHODS: A prospective cohort of one hundred and thirty-two
      consecutive patients who underwent ACL reconstruction between 2005 and 2009 were
      analysed. The median age of the patients was 18 years (12-57). Sixteen patients
      were excluded due to chronic ACL injury. RESULTS: One hundred and sixteen
      patients (117 ACL ruptures) were included in the analysis. A typical injury
      pattern was documented in 87 (74.4 %) of cases. The most common sporting
      activities associated with an ACL injury were football (35.3 %), skiing (21.6 %)
      and rugby (10.3 %). The majority of patients (67.5 %) sought medical attention
      within 1 week from time of injury. The correct diagnosis of an ACL rupture was
      made in 33 cases (28.2 %) at the initial medical consultation. The diagnosis was
      made following medical consultation in 13 (11.1 %) of cases with the use of
      magnetic resonance imaging and 6 (5.1 %) cases at arthroscopy. The median time to
      diagnosis was 6 weeks (0-192), and the median time to ACL reconstruction was 24
      weeks (1-240). A delay in diagnosis of >6 months was associated with a medial
      meniscal tear rate of 72.2 % compared to 23.1 % if the diagnosis was made within
      4 months of the injury (p < 0.05). CONCLUSIONS: Despite a 'typical' mechanism of
      injury leading to ACL rupture, the rate of initial diagnosis in the UK still
      remains poor. This often leads to an unnecessary delay in the diagnosis and
      subsequent treatment and increases the risk of secondary injury to the knee. A
      delay in diagnosis of >6 months was associated with an increased medial meniscal
      tear rate. Patients who present with a 'typical' injury pattern should therefore
      be referred for further assessment by a knee specialist within 6 weeks. LEVEL OF
      EVIDENCE: IV.

PMID- 24671386
TI  - Influence of partial meniscectomy on attachment forces, superficial strain and
      contact mechanics in porcine knee joints.
AB  - PURPOSE: Numerous studies investigated the reasons for premature osteoarthritis
      due to partial meniscectomy (PM). However, the influence of meniscectomy on
      attachment forces and superficial strain of the tibial meniscus is unclear. It is
      hypothesised that these parameters depend on the degree of PM. METHODS: Six
      porcine medial menisci were placed in a custom made apparatus, and each meniscal
      attachment was connected to a force sensor. After printing markers onto the
      tibial meniscal surfaces, the menisci were positioned on a glass plate enabling
      optical superficial strain measurement. Additionally, contact area and pressure
      were investigated. Each meniscus was axially loaded up to 650 N using its
      respective femoral condyle. Testing was conducted intact and after 50 and 75% PM
      of the posterior horn and extending 75% PM to the anterior horn. RESULTS: With
      increasing meniscectomy, the attachment forces decreased anteriorly by up to 17%
      (n.s.) and posteriorly by up to 55% (p = 0.003). The circumferential strain in
      the peripheral meniscal zones was not affected by the meniscectomy, while in some
      meniscal zones the radial strain changed from compression to tension. Contact
      area decreased by up to 23% (p = 0.01), resulting in an increase in 40% (p =
      0.02) for the maximum contact pressure. CONCLUSION: Partial meniscectomy
      significantly alters the loading situation of the meniscus and its attachments.
      Specifically, the attachment forces decreased with increasing amount of meniscal
      tissue loss, which reflects the impaired ability of the meniscus to transform
      axial joint load into meniscal hoop stress.

PMID- 24671387
TI  - The use of patient-specific instruments does not reduce blood loss during
      minimally invasive total knee arthroplasty?
AB  - PURPOSE: Blood loss can be substantial and will influence morbidity and mortality
      after total knee arthroplasty. This study evaluated whether patient-specific
      instruments (PSI) can reduce blood loss because the intramedullary canal is not
      opened during the procedure and whether hidden blood loss can be reduced by its
      use. METHODS: Seventy-five patients operated with the Signature PSI technique
      were compared with a matched group operated with conventional instruments.
      Maximal drop in haemoglobin (Hb) and hematocrit (HTC) level were compared at day
      2 and day 4. Transfusions were noted. Clinical outcomes like range of motion and
      knee society scores were studied as secondary outcomes. RESULTS: No statistically
      significant difference for calculated blood loss, maximal drop in Hb or HTC and
      transfusions were found. No clinical differences in range of motion or knee
      society scores were observed. CONCLUSIONS: The use of PSI-assisted total knee
      arthroplasty (TKA) did not result in less blood loss compared with conventional
      minimally invasive TKA with tourniquet. No reduction in hidden blood loss was
      observed either. According to this study, the argument of reduced transfusion
      cost should not be used in cost-effectiveness calculations of PSI-assisted TKA.
      LEVEL OF EVIDENCE: III.

PMID- 24671389
TI  - Frontier microfluidic techniques for short and long-term single cell analysis.
AB  - Here, we review the frontier microfluidic techniques for single cell analysis
      (SCA), which is important for research of many biological systems. Microfluidics
      provides high-throughput, high-resolution experiments at low cost and reagent
      use, making it especially useful for single cell analysis. Recent advancements in
      the field have made SCA more feasible, improving device throughput and
      resolution, adding capabilities, and combining different functions to bring forth
      new assays. Developments in incubation have allowed for long-term cell tracking
      assays to be performed with single cell resolution. The ability of systems to
      provide chemical isolation or prolonged growth of adherent cells is also
      discussed. 

PMID- 24671388
TI  - Efficacy of intraarticular application of ketamine or ketamine-levobupivacaine
      combination on post-operative pain after arthroscopic meniscectomy.
AB  - PURPOSE: To evaluate the efficacy of intraarticular injection of ketamine or
      ketamine plus levobupivacaine on post-operative analgesia in patients undergoing
      arthroscopic meniscectomy. METHODS: A prospective, randomized, double-blind study
      was performed on 60 patients aged 18-65 years who planned to undergo elective
      arthroscopic meniscectomy. The patients were divided into three groups: the
      ketamine group (n = 20) received 1.0 mg/kg of intraarticular ketamine in 20 ml of
      normal saline, the ketamine-levobupivacaine group (n = 20) received 0.5 mg/kg of
      intraarticular ketamine plus 50.0 mg of 0.25 % levobupivacaine in 20 ml of normal
      saline, and the control group (n = 20) received 20 ml of intraarticular normal
      saline. A visual analogue scale (VAS) was used to determine the efficacy of
      analgesia at 1, 2, 4, 6, 8, 12, and 24 h post-operatively. RESULTS: There were
      statistically significant differences in the median VAS scores among the three
      groups according to Bonferroni adjustment at all time points (p < 0.01), with the
      exception of 6 and 24 h post-operatively. The median VAS scores at 1, 2, and 4 h
      post-operatively were higher in the control group than in the two treatment
      groups (p < 0.001). The median VAS scores in the control group at 1, 2, 4, 6, 8,
      and 12 h post-operatively and those in the ketamine group at 4, 8, and 12 h post
      operatively were significantly higher than those in the ketamine-levobupivacaine
      group (p < 0.05). CONCLUSION: Intraarticular ketamine provides effective post
      operative analgesia. Addition of intraarticular levobupivacaine to ketamine may
      provide better amelioration of pain after outpatient arthroscopic meniscectomy.

PMID- 24671390
TI  - Migraine and reward system-or is it aversive?
AB  - Migraine is a debilitating neurological disorder with grave consequences for both
      the individual and society. This review will focus on recent literature
      investigating how brain structures implicated in reward and aversion contribute
      to the genesis of migraine pain. There exist many overlapping and interacting
      brain regions within pain and reward circuitry that contribute to negative affect
      and subjective experience of pain. The emotional component of pain has been
      argued to be a greater metric of quality of life than its sensory component, and
      thus understanding the processes that influence this pain characteristic is
      essential to developing novel treatment strategies for mitigating migraine pain.
      We emphasize and provide evidence that abnormalities within the mesolimbic
      cortical reward pathways contribute to migraine pain and that there are
      structural and functional neuroplasticity within the overlapping brain regions
      common to both pain and reward. 

PMID- 24671392
TI  - Structural imaging in cluster headache.
AB  - Cluster headache is a rare primary headache disorder and the most common
      trigeminal-autonomic cephalalgia. Even though it has been extensively studied,
      its pathophysiology remains nebulous. Over the last two decades, cerebral imaging
      has increasingly been used to aid the investigation of pain and headache
      disorders. Pioneering work using magnetic resonance-based, voxel-based
      morphometry depicted an isolated increase of grey matter in the posterior
      hypothalamus and thereby reconfirmed the most commonly accepted
      pathophysiological concept. More recent works demonstrate structural changes
      across multiple structures related to pain processing, sensory integration, and
      emotional evaluation. These changes do not seem to be static, but rather appear
      to be dynamic in nature as they change over the course of the disease. This was
      interpreted as a reflection of the plasticity of the human brain and should guide
      future thoughts towards a more complex pathophysiological model involving a
      maladaptive pain modulatory network. 

PMID- 24671391
TI  - Peripheral neuromodulation: a review.
AB  - Peripheral nerve stimulation (PNS) is likely the most diverse and rapidly
      expanding area of neuromodulation. Its expansion has become possible due to both
      technological and clinical advances in pain medicine. The first implantable
      systems were surgically placed. However, it is currently commonplace to use
      percutaneous leads, as this approach has become instrumental in its expansion.
      The first percutaneous peripheral nerve stimulators were reported in 1999.
      Cylindrical leads were implanted to stimulate the greater occipital nerve to
      manage intractable headache. It has been expanded into other individual nerves or
      nerve plexuses to treat neuropathic, visceral, cardiac, abdominal, low back and
      facial pain. The use of PNS in modulating organ function in treatment of
      syndromes such as epilepsy, incontinence and obesity with vagal, tibial and
      gastric stimulation is under extensive investigation. New technologies that allow
      easier and safer electrode placement are expected to further expand the uses of
      PNS. A noninvasive stimulation will open this treatment modality to more
      clinicians of varying backgrounds. 

PMID- 24671393
TI  - Optimization of integrated water quality management for agricultural efficiency
      and environmental conservation.
AB  - The scarcity of water resources in Egypt has necessitated the use of various
      types of lower quality water. Agricultural drainage water is considered a
      strategic reserve for meeting increasing freshwater demands. In this study, a
      novel model series was applied to a drainage basin in the Nile Delta to optimize
      integrated water quality management for agriculture and the aquatic environment.
      The proposed model series includes a waste load allocation model, an export
      coefficient model, a stream water quality model, and a genetic algorithm. This
      model series offers an optimized solution for determining the required removal
      levels of total suspended solids (TSS), the chemical oxygen demand (COD) at point
      and non-point pollution sources, and the source flows that require treatment to
      meet a given water quality target. The model series was applied during the summer
      and winter to the El-Qalaa basin in the western delta of the Nile River.
      Increased pollutant removal and treated fractions at point and non-point sources
      reduced violations of the TSS standards from 732.6 to 238.9 mg/L in summer and
      from 543.1 to 380.9 mg/L in winter. Likewise, violations of the COD standards
      decreased from 112.4 mg/L to 0 (no violations) in summer and from 91.7 mg/L to no
      violations in winter. Thus, this model is recommended as a decision support tool
      for determining a desirable waste load allocation solution from a trade-off curve
      considering costs and the degree of compliance with water quality standards.

PMID- 24671394
TI  - Simultaneous separation of apigenin, luteolin and rosmarinic acid from the aerial
      parts of the copper-tolerant plant Elsholtzia splendens.
AB  - Elsholtzia splendens is a copper-tolerant plant species which grows on copper
      deposits in China. The generation of a valuable E. splendens biomass on specific
      contaminated sites has become one of the promising phytotechnologies. The
      simultaneous separations of apigenin, luteolin, and rosmarinic acid yielded in
      the ethyl acetate extracts of the flowering aerial parts was achieved by the use
      of a macroporous resin, polyamide, and silicagel columns during chromatography.
      Chemical identification confirmed the structures based on the spectra of FTIR,
      NMR, and HPLC/ESI-MS. The isolated compounds of purity above 98.3% were evaluated
      for their in vitro cytotoxic activities against human cancer cell lines including
      A549 (non-small lung), A431 (skin), and Bcap37 (breast). Among these compounds,
      luteolin and apigenin presented the best cytotoxic activities against A549, A431,
      and Bcap37 cells and, therefore, both could be the valuable products for the post
      harvest processing of E. splendens biomass.

PMID- 24671395
TI  - Efficiency of a cleanup technology to remove mercury from natural waters by means
      of rice husk biowaste: ecotoxicological and chemical approach.
AB  - In the present work, the efficiency of rice husk to remove Hg(II) from river
      waters spiked with realistic environmental concentrations of this metal (MUg L(
      1) range) was evaluated. The residual levels of Hg(II) obtained after the
      remediation process were compared with the guideline values for effluents
      discharges and water for human consumption, and the ecotoxicological effects
      using organisms of different trophic levels were assessed. The rice husk sorbent
      proved to be useful in decreasing Hg(II) contamination in river waters, by
      reducing the levels of Hg(II) to values of ca. 8.0 and 34 MUg L(-1), for an
      Hg(II) initial concentration of 50 and 500 MUg L(-1), respectively. The
      remediation process with rice husk biowaste was extremely efficient in river
      waters spiked with lower levels of Hg(II), being able to eliminate the toxicity
      to the exposed organisms algae Pseudokirchneriella subcapitata and rotifer
      Brachionus calyciflorus and ensure the total survival of Daphnia magna species.
      For concentrations of Hg(II) tenfold higher (500 MUg L(-1)), the remediation
      process was not adequate in the detoxification process, still, the rice husk
      material was able to reduce considerably the toxicity to the bacteria Vibrio
      fischeri, algae P. subcapitata and rotifer B. calyciflorus, whose responses where
      fully inhibited during its exposure to the non-remediated river water. The use of
      a battery of bioassays with organisms from different trophic levels and whose
      sensitivity revealed to be different and dependent on the levels of Hg(II)
      contamination proved to be much more accurate in predicting the ecotoxicological
      hazard assessment of the detoxification process by means of rice husk biowaste. 

PMID- 24671396
TI  - Low-cost adsorbent prepared from sewage sludge and corn stalk for the removal of
      COD in leachate.
AB  - Sewage sludge (SS) with corn stalk (CS) was used to prepare SS-based activated
      carbon (SAC) by pyrolysis with ZnCl2. The effects of mixing ratio on surface area
      and pore size distribution, elemental composition, surface chemistry, and
      morphology were investigated. The results demonstrated that the addition of CS
      into SS samples improved the surface area (from 92 to 902 m(2)/g) and the
      microporosity (from 1.2 to 4.1%) of the adsorbents and, therefore, enhancing the
      adsorption performance. The removal of leachate chemical oxygen demand (COD) was
      also determined. It was found that the COD removal rate reached 85% at pH 4 with
      the SAC (90 wt% CS) dosage of 2% (g/mL) and an adsorption time of 40 min. The
      adsorption experimental data were fitted by both Langmuir and Freundlich
      adsorption isotherms. Long-chain alkanes and refractory organics were found in
      raw leachate, but could be removed by SAC largely.

PMID- 24671377
TI  - Regulation of cellular communication by signaling microdomains in the blood
      vessel wall.
AB  - It has become increasingly clear that the accumulation of proteins in specific
      regions of the plasma membrane can facilitate cellular communication. These
      regions, termed signaling microdomains, are found throughout the blood vessel
      wall where cellular communication, both within and between cell types, must be
      tightly regulated to maintain proper vascular function. We will define a cellular
      signaling microdomain and apply this definition to the plethora of means by which
      cellular communication has been hypothesized to occur in the blood vessel wall.
      To that end, we make a case for three broad areas of cellular communication where
      signaling microdomains could play an important role: 1) paracrine release of free
      radicals and gaseous molecules such as nitric oxide and reactive oxygen species;
      2) role of ion channels including gap junctions and potassium channels,
      especially those associated with the endothelium-derived hyperpolarization
      mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable
      oversight by signaling microdomains, especially those associated with the release
      of von Willebrand factor. When summed, we believe that it is clear that the
      organization and regulation of signaling microdomains is an essential component
      to vessel wall function. 

PMID- 24671397
TI  - Genotoxic assessment and optimization of pressmud with the help of exotic
      earthworm Eisenia fetida.
AB  - Genotoxicity of pressmud (PM) to Allium cepa was investigated to assess its toxic
      potential and to elucidate the effect of vermicomposting to reduce its toxicity.
      The PM produced as a waste by product of the sugar cane industry was mixed with
      cow dung (CD) at different ratios of 0:100 (V0), 25:75 (V25), 50:50 (V50), 75:25
      (V75) and 100:0 (V100) (PM:CD) on a dry weight basis for vermicomposting with
      Eisenia fetida. Different concentrations of 100% PM sludge extract (10%, 20%,
      40%, 60%, 80% and 100%) and negative control (distilled water) and positive
      control (maleic hydrazide) were analyzed with A. cepa assay to evaluate frequency
      of chromosomal aberrations before and after vermicomposting. Percent aberration
      was greatest (30.8%) after exposure to 100% PM extract after 6 h but was reduced
      to 20.3% after vermicomposting. Exposure to the extract induced c-mitosis,
      delayed anaphase, laggards, stickiness and vagrant aberrations. Microscopic
      examination of root meristem exposed to PM sludge extract showed significant
      inhibition of mitotic index. Also, the mitotic index decreased with increase in
      concentration of PM sludge extract. After vermicomposting the mitotic index was
      increased. However, increasing percentages of PM significantly affected the
      growth and fecundity of the worms and maximum population size was reached in the
      25:75 (PM:CD) feed mixture. Nitrogen, phosphorus, sodium, electrical conductivity
      (EC) and pH increased from initial feed mixture to the final products (i.e.,
      vermicompost), while organic carbon, C/N ratio and potassium declined in all
      products of vermicomposting. Scanning electron microscopy (SEM) was recorded to
      identify the changes in texture with numerous surface irregularities and high
      porosity that proves to be good vermicompost manure. It could be concluded that
      vermicomposting could be an important tool to reduce the toxicity of PM as
      evidenced by the results of genotoxicity.

PMID- 24671399
TI  - Decontamination of produced water containing petroleum hydrocarbons by
      electrochemical methods: a minireview.
AB  - Produced water (PW) is the largest waste stream generated in oil and gas
      industries. The drilling and extraction operations that are aimed to maximize the
      production of oil may be counterbalanced by the huge production of contaminated
      water (called PW) with pollutants, such as heavy metals, dissolved/suspended
      solids, and organic compounds. PW is conventionally treated through different
      physical, chemical, and biological methods. In offshore platforms, because of
      space constraints, compact physical and chemical systems are used. However, major
      research efforts are being developed with innovative technologies for treating PW
      in order to comply with reuse and discharge limits. Among them, electrochemical
      technologies have been proposed as a promising alternative for the treatment of
      this kind of wastewaters. Then, this paper presents a minireview of efficient
      electrochemical technologies used until now for treating PW generated by
      petrochemical industry. 

PMID- 24671400
TI  - Sequential electrochemical treatment of dairy wastewater using aluminum and DSA
      type anodes.
AB  - Dairy wastewater is characterized by a high content of hardly biodegradable
      dissolved, colloidal, and suspended organic matter. This work firstly
      investigates the performance of two individual electrochemical treatments, namely
      electrocoagulation (EC) and electro-oxidation (EO), in order to finally assess
      the mineralization ability of a sequential EC/EO process. EC with an Al anode was
      employed as a primary pretreatment for the conditioning of 800 mL of wastewater.
      A complete reduction of turbidity, as well as 90 and 81% of chemical oxygen
      demand (COD) and total organic carbon (TOC) removal, respectively, were achieved
      after 120 min of EC at 9.09 mA cm(-2). For EO, two kinds of dimensionally stable
      anodes (DSA) electrodes (Ti/IrO2-Ta2O5 and Ti/IrO2-SnO2-Sb2O5) were prepared by
      the Pechini method, obtaining homogeneous coatings with uniform composition and
      high roughness. The (.)OH formed at the DSA surface from H2O oxidation were not
      detected by electron spin resonance. However, their indirect determination by
      means of H2O2 measurements revealed that Ti/IrO2-SnO2-Sb2O5 is able to produce
      partially physisorbed radicals. Since the characterization of the wastewater
      revealed the presence of indole derivatives, preliminary bulk electrolyses were
      done in ultrapure water containing 1 mM indole in sulfate and/or chloride media.
      The performance of EO with the Ti/IrO2-Ta2O5 anode was evaluated from the TOC
      removal and the UV/Vis absorbance decay. The mineralization was very poor in 0.05
      M Na2SO4, whereas it increased considerably at a greater Cl(-) content, meaning
      that the oxidation mediated by electrogenerated species such as Cl2, HClO, and/or
      ClO(-) competes and even predominates over the (.)OH-mediated oxidation. The EO
      treatment of EC-pretreated dairy wastewater allowed obtaining a global 98 % TOC
      removal, decreasing from 1,062 to <30 mg L(-1).

PMID- 24671398
TI  - Chronic dietary exposure to pyrolytic and petrogenic mixtures of PAHs causes
      physiological disruption in zebrafish--part II: behavior.
AB  - In the last 10 years, behavior assessment has been developed as an indicator of
      neurotoxicity and an integrated indicator of physiological disruption. Polycyclic
      aromatic hydrocarbon (PAH) release into the environment has increased in recent
      decades resulting in high concentrations of these compounds in the sediment of
      contaminated areas. We evaluated the behavioral consequences of long-term chronic
      exposure to PAHs, by exposing zebrafish to diets spiked with three PAH fractions
      at environmentally relevant concentrations. Fish were exposed to these chemicals
      from their first meal (5 days postfertilization) until they became reproducing
      adults (at 6 months old). The fractions used were representative of PAHs of
      pyrolytic (PY) origin and of two oils differing in composition (a heavy fuel oil
      (HO) and a light crude oil (LO)). Several tests were carried out to evaluate
      circadian spontaneous swimming activity, responses to a challenge (photomotor
      response), exploratory tendencies, and anxiety levels. We found that dietary PAH
      exposure was associated with greater mobility, lower levels of exploratory
      activity, and higher levels of anxiety, particularly in fish exposed to the HO
      fraction and, to a lesser extent, the LO fraction. Finally, our results indicate
      that PAH mixtures of different compositions, representative of situations
      encountered in the wild, can induce behavioral disruptions resulting in poorer
      fish performance.

PMID- 24671401
TI  - Efficient removal of insecticide "imidacloprid" from water by electrochemical
      advanced oxidation processes.
AB  - The oxidative degradation of imidacloprid (ICP) has been carried out by
      electrochemical advanced oxidation processes (EAOPs), anodic oxidation, and
      electro-Fenton, in which hydroxyl radicals are generated electrocatalytically.
      Carbon-felt cathode and platinum or boron-doped diamond (BDD) anodes were used in
      electrolysis cell. To determine optimum operating conditions, the effects of
      applied current and catalyst concentration were investigated. The decay of ICP
      during the oxidative degradation was well fitted to pseudo-first-order reaction
      kinetics and absolute rate constant of the oxidation of ICP by hydroxyl radicals
      was found to be k abs(ICP) = 1.23 * 10(9) L mol(-1) s(-1). The results showed
      that both anodic oxidation and electro-Fenton process with BDD anode exhibited
      high mineralization efficiency reaching 91 and 94% total organic carbon (TOC)
      removal at 2 h, respectively. For Pt-EF process, mineralization efficiency was
      also obtained as 71%. The degradation products of ICP were identified and a
      plausible general oxidation mechanism was proposed. Some of the main reaction
      intermediates such as 6-chloronicotinic acid, 6-chloronicotinaldehyde, and 6
      hydroxynicotinic acid were determined by GC-MS analysis. Before complete
      mineralization, formic, acetic, oxalic, and glyoxylic acids were identified as
      end-products. The initial chlorine and organic nitrogen present in ICP were found
      to be converted to inorganic anions Cl(-), NO3(-), and NH4(+).

PMID- 24671402
TI  - Correlations between PAH bioavailability, degrading bacteria, and soil
      characteristics during PAH biodegradation in five diffusely contaminated
      dissimilar soils.
AB  - The natural biodegradation of seven polycyclic aromatic hydrocarbons (PAHs) by
      native microorganisms was studied in five soils from Normandy (France) from
      diffusely polluted areas, which can also pose a problem in terms of surfaces and
      amounts of contaminated soils. Bioavailability tests using cyclodextrin-based
      extractions were performed. The natural degradation of low molecular weight (LMW)
      PAHs was not strongly correlated to their bioavailability due to their sorption
      to geosorbents. Conversely, the very low degradation of high molecular weight
      (HMW) PAHs was partly correlated to their poor availability, due to their
      sorption on complexes of organic matter and kaolinites or smectites. A principal
      component analysis allowed us to distinguish between the respective degradation
      behaviors of LMW and HMW PAHs. LMW PAHs were degraded in less than 2-3 months and
      were strongly influenced by the relative percentage of phenanthrene-degrading
      bacteria over total bacteria in soils. HMW PAHs were not significantly degraded,
      not only because they were less bioavailable but also because of a lack of
      degrading microorganisms. Benzo[a]pyrene stood apart since it was partly degraded
      in acidic soils, probably because of a catabolic cooperation between bacteria and
      fungi.

PMID- 24671404
TI  - Back-table tailored stent grafts: surgeon modified, surgeon approved.

PMID- 24671403
TI  - Mammalian cell line-based bioassays for toxicological evaluation of landfill
      leachate treated by Pseudomonas sp. ISTDF1.
AB  - Landfill leachate has become a serious environmental concern because of the
      presence of many hazardous compounds which even at trace levels are a threat to
      human health and environment. Therefore, it is important to assess the toxicity
      of leachate generated and discharge it conforming to the safety standards. The
      present work examined the efficiency of an earlier reported Pseudomonas sp.
      strain ISTDF1 for detoxification of leachate collected from Okhla landfill site
      (New Delhi, India). GC-MS analysis performed after treatment showed the removal
      of compounds like alpha-limonene diepoxide, brominated dioxin-2-one, Bisphenol A,
      nitromusk, phthalate derivative, and nitrobenzene originally found in untreated
      leachate. ICP-AES analysis for heavy metals also showed reduction in
      concentrations of Zn, Cd, Cr, Fe, Ni, and Pb bringing them within the limit of
      safety discharge. Methyl tetrazolium (MTT) assay for cytotoxicity, alkaline comet
      assay for genotoxicity, and 7-ethoxyresorufin-O-deethylase (EROD) assay for
      dioxin-like behavior were carried out in human hepato-carcinoma cell line HepG2
      to evaluate the toxic potential of treated and untreated leachates. The bacterium
      reduced toxicity as shown by 2.5-fold reduction of MTT EC50 value, 7-fold
      reduction in Olive Tail Moment, and 2.8-fold reduction in EROD induction after
      240 h of bacterial treatment.

PMID- 24671405
TI  - Methanol-inducible promoter of thermotolerant methylotrophic yeast Ogataea
      thermomethanolica BCC16875 potential for production of heterologous protein at
      high temperatures.
AB  - Methanol-utilizing metabolism is generally found in methylotrophic yeasts.
      Several potential promoters regulating enzymes in this pathway have been
      extensively studied, especially alcohol oxidase. Here, we characterized the
      alcohol oxidase gene promoter from thermotolerant Ogataea thermomethanolica
      (OthAOX). This promoter can be induced by methanol, and was shown to regulate
      expression of phytase up to 45  degrees C. The pattern of heterologous phytase N
      glycosylation depends on the induction temperature. Unlike the AOX promoter from
      Pichia pastoris, this OthAOX initially turns on the expression of the
      heterologous protein at the de-repression stage in the presence of glycerol. Full
      induction of protein is observed when methanol is present. With this methanol
      inducible promoter, target protein can be initially produced prior to the
      induction phase, which would help shorten the time for protein production. Being
      able to drive protein expression at various temperatures prompts this newly
      identified AOX promoter to be potential tool for heterologous protein production
      in high temperature conditions.

PMID- 24671406
TI  - Application of redundancy analysis for aerobiological data.
AB  - An aerobiological survey was conducted through five consecutive years (2006-2010)
      at Worcester (England). The concentration of 20 allergenic fungal spore types was
      measured using a 7-day volumetric spore trap. The relationship between
      investigated fungal spore genera and selected meteorological parameters (maximum,
      minimum, mean and dew point temperatures, rainfall, relative humidity, air
      pressure, wind direction) was examined using an ordination method (redundancy
      analysis) to determine which environmental factors favoured their most abundance
      in the air and whether it would be possible to detect similarities between
      different genera in their distribution pattern. Redundancy analysis provided
      additional information about the biology of the studied fungi through the results
      of the Spearman's rank correlation. Application of the variance inflation factor
      in canonical correspondence analysis indicated which explanatory variables were
      auto-correlated and needed to be excluded from further analyses. Obtained
      information will be consequently implemented in the selection of factors that
      will be a foundation for forecasting models for allergenic fungal spores in the
      future. 

PMID- 24671407
TI  - Bioclimatic comfort and the thermal perceptions and preferences of beach
      tourists.
AB  - The largest market segment of global tourism is coastal tourism, which is
      strongly dependent on the destination's thermal climate. To date, outdoor
      bioclimatic comfort assessments have focused exclusively on local residents in
      open urban areas, making it unclear whether outdoor comfort is perceived
      differently in non-urban environments or by non-residents (i.e. tourists) with
      different weather expectations and activity patterns. This study provides needed
      insight into the perception of outdoor microclimatic conditions in a coastal
      environment while simultaneously identifying important psychological factors that
      differentiate tourists from everyday users of urban spaces. Concurrent
      micrometeorological measurements were taken on several Caribbean beaches in the
      islands of Barbados, Saint Lucia and Tobago, while a questionnaire survey was
      used to examine the thermal comfort of subjects (n = 472). Universal Thermal
      Climate Index (UTCI) conditions of 32 to 39  degrees C were recorded, which were
      perceived as being "slightly warm" or "warm" by respondents. Most beach users (48
      to 77 %) would not change the thermal conditions, with some (4 to 15 %)
      preferring even warmer conditions. Even at UTCI of 39  degrees C, 62 % of
      respondents voted for no change to current thermal conditions, with an additional
      10 % stating that they would like to feel even warmer. These results indicate
      that beach users' thermal preferences are up to 18  degrees C warmer than the
      preferred thermal conditions identified in existing outdoor bioclimatic studies
      from urban park settings. This indicates that beach users hold fundamentally
      different comfort perceptions and preferences compared to people using urban
      spaces. Statistically significant differences (p <= .05) were also recorded for
      demographic groups (gender, age) and place of origin (climatic region). 

PMID- 24671408
TI  - Interspecific differences in whole-plant respiration vs. biomass scaling
      relationships: a case study using evergreen conifer and angiosperm tree
      seedlings.
AB  - PREMISE OF THE STUDY: Empirical studies and theory indicate that respiration
      rates (R) of small plants scale nearly isometrically with both leaf biomass (ML)
      and total plant biomass (MT). These predictions are based on angiosperm species
      and apply only across a small range of body mass. Whether these relationships
      hold true for different plants, such as conifers, remains unclear. METHODS: We
      tested these predictions using the whole-plant maintenance respiration rates and
      the biomass allocation patterns of the seedlings of two conifer tree species and
      two angiosperm tree species. Model Type II regression protocols were used to
      compare the scaling exponents (alpha) and normalization constants (beta) across
      all four species and within each of the four species. KEY RESULTS: The data show
      that the scaling exponents varied among the four species and that all differed
      significantly from isometry. For conifers, scaling exponents for R vs. MT, and R
      and ML were numerically smaller than those of the broadleaved angiosperm species.
      However, across the entire data set, R scaled isometrically with ML and with MT
      as predicted by the West, Brown, and Enquist (WBE) theory. We also observed
      higher respiration rates for small conifer seedlings compared to comparably sized
      angiosperm seedlings. CONCLUSIONS: Our data add credence to the view that the R
      vs. M scaling relationship differs among species, and that in general, the
      numerical values of this interspecific scaling relationship will depend on the
      species pooled in the analysis and on the range of body sizes within the data
      set.

PMID- 24671409
TI  - Photophysical properties of a new water soluble tetra thiamine substituted zinc
      phthalocyanine conjugated to gold nanorods of different aspect ratios.
AB  - A water soluble zinc phthalocyanine substituted with thiamine is reported in this
      work. The aggregation of this compound in aqueous solutions causes quenching of
      the fluorescence quantum yields. Gold nanospheres and nanorods were linked to the
      phthalocyanine. X-ray photoelectron spectroscopy showed that both the amine and
      the sulphur groups on the thiamine substituent of the zinc phthalocyanine were
      involved in the linking to gold nanoparticles. The Pc showed an increase in the
      fluorescence quantum yields in the presence of the nanoparticles. The singlet
      oxygen quantum yield increased when the Pc was conjugated to the nanoparticles
      and even higher for larger aspect ratio gold nanorods. 

PMID- 24671410
TI  - Detainees in police custody in the Paris, France area: medical data and high-risk
      situations (a prospective study over 1 year).
AB  - BACKGROUND AND OBJECTIVE: The annual number of detainees held in police custody
      in France is approximately 700,000. Medical data regarding arrestees are scarce
      across countries. We present the medical characteristics of detainees kept in
      police custody, including addictive behaviours and high-risk medical situations.
      METHODS: We conducted a prospective study over 1 year in a suburban area near
      Paris. RESULTS: A total of 19,098 medical examinations were performed on 13,317
      individuals. The examinations mainly concerned male subjects (18,116 of 19,098,
      95 %). Median age was 24 years (range 13-83). Medical examination was requested
      by the detainee in 6,638 of 16,801 cases (40 %). Assaults were reported in 4,052
      of 17,312 cases (23 %) and occurred at the time of arrest in most cases (2,243,
      13 %). A total of 2,394 of 13,317 detainees (18 %) had at least one chronic
      somatic disorder including asthma (603, 5 %), diabetes (263, 2 %) and arterial
      hypertension (205, 2 %). A history of psychiatric disorder was reported by 6 % of
      individuals (674 of 11,787). Regular alcohol drinking was reported by 58 % of
      detainees. Illicit drug use mainly involved cannabis (4,021 cases, 30 %). In
      14,661 of 19,098 cases (77 %), detainees were considered to be unconditionally
      fit for detention in custody, and 274 detainees (1 %) were declared unfit to be
      detained. CONCLUSION: The present study showed a high frequency of alcohol or
      substance use and reported assaults or traumatic lesions in arrestees. Attending
      physicians should pay particular attention to addictive behaviours and traumatic
      injuries in arrestees, both for immediate care and for prevention.

PMID- 24671412
TI  - Solid state chemistry of nitrogen oxides--part I: surface consumption of NO.
AB  - The role of nitrogen and oxygen chemistry in the interstellar medium is still
      rather poorly understood. Nitric oxide, NO, has been proposed as an important
      precursor in the formation of larger N- and O-bearing species, such as
      hydroxylamine, NH2OH, and nitrogen oxides, NO2 and N2O. The topic of this study
      is the solid state consumption of NO via oxygenation and the formation of NO2 and
      other nitrogen oxides (ONNO2 and N2O4) under conditions close to those
      encountered on icy grains in quiescent interstellar clouds. In our experiments
      nitric oxide and oxygen allotropes (O, O2, and O3) or N atoms are co-deposited
      under ultra-high vacuum conditions on different substrates (silicate, graphite,
      compact ASW ice, and gold) at temperatures ranging between 10 and 35 K. Reaction
      products are monitored via Fourier Transform Reflection Absorption Infrared
      Spectroscopy (FT-RAIRS) and Temperature Programmed Desorption (TPD) using mass
      spectrometry. We find that NO2 is efficiently formed in NO + O/O2/O3/N solid
      surface reactions. These are essentially barrier free and offer a pathway for the
      formation of NO2 in space. Nitrogen dioxide, however, has not been astronomically
      detected, contradicting the efficient reaction channel found here. This is likely
      due to other pathways, including regular hydrogenation reactions, as discussed
      separately in part II of this study. 

PMID- 24671411
TI  - Are hip hemiarthroplasty and total hip arthroplasty infections different
      entities? The importance of hip fractures.
AB  - Hip hemiarthroplasty (HHA) and total hip arthroplasty (THA) infections are
      usually considered as one entity; however, they may show important differences.
      We analyze these differences, as well as predictors of treatment failure (TF) and
      poor functional status among patients with prosthetic hip infections (PHIs). A
      multicenter cohort study of consecutive patients with PHIs was performed. The
      main outcome variable was TF after the first surgical treatment performed to
      treat the infection. Multivariate analysis was used to identify predictors of TF.
      A total of 127 patients with PHI were included (43 HHA, 84 THA). Patients with
      HHA infections were more frequently women (88% vs. 54%; p < 0.001), had
      comorbidities (86% vs. 67%, p = 0.02), and were older (median age 79 vs. 65
      years, p < 0.001), and the reason for arthroplasty was more frequently a fracture
      (100% vs. 18%, p < 0.001). Failure of initial treatment and crude mortality were
      more frequent among HHA patients (44% vs. 23%, p = 0.01 and 28% vs. 7%, p =
      0.001, respectively). However, HHA was not associated with TF in the multivariate
      analysis when hip fracture was considered; thus, variables independently
      associated with TF were hip fracture, inadequate surgical management, prosthesis
      retention, and higher C-reactive protein level. Failure of the first surgical
      treatment was associated with poorer functional status. HHA and THA infections
      showed significant differences in epidemiology, clinical features, and outcome.
      Although patients with HHA infections had a higher risk of TF, this was related
      to the reason for hip implant: a hip fracture. Success of the initial management
      of infection is a predictor of better clinical and functional outcome.

PMID- 24671413
TI  - Parameters that affect macromolecular self-assembly of prion protein.
AB  - Amyloidogenesis of prion protein (PrP) is closely associated with the
      pathobiology of prion diseases. To understand details on formation of PrP
      amyloids, we investigated various conditions that influence the process in vitro,
      using full length and truncated recombinant PrP. Disrupted agitation and
      fluctuated temperature resulted in prolongation of lag phase during PrP amyloid
      formation. With the same conditions and material for the assay, fluorescence
      microplate readers of different manufacturers, which are assumed to have
      incongruent level of mechanical performance, demonstrated variations for the
      length of lag phase and the level of fluorescence detection. Presence of
      preformed amyloid seeds accelerated PrP amyloid formation. Similarly, recombinant
      proteins of different species affected effectual generation of amyloids. This
      process was also influenced by the concentrations and truncation of recombinant
      PrP. By investigating several conditions to perform PrP amyloid formation assay,
      our study addresses the factors that determine how much and how rapidly PrP
      amyloids are formed. 

PMID- 24671414
TI  - Amplification by nucleic acid-templated reactions.
AB  - Nucleic acid-templated reactions enable the design of conditional reaction
      systems, in which bond formation occurs only when a particular DNA or RNA
      molecule is present. Such reaction systems are currently being explored for
      applications in DNA/RNA diagnosis, drug screening and as a means to design gene
      expression specific therapy. However, biological nucleic acid templates usually
      have low abundance. Therefore, either the targeted nucleic acid template has to
      be multiplied by means of an amplification step or the template itself has to act
      as a catalyst which amplifies product formation. This critical review highlights
      the recent advancements in nucleic acid-templated reactions that proceed with
      turnover in template and thereby provide a means of amplification. Improvements
      in reaction engineering and the development of new chemistries have pushed the
      limits from 10(1) to 10(2)-10(3) turnovers. This includes reaction systems that
      lead to the ligation of oligonucleotides or to the interconversion of appended
      functional groups beyond ligation as well as templated chemistries that enable
      the activation of catalysts for subsequent triggering of reactions between non
      nucleotidic substrates. The present limitations and future opportunities are
      discussed. 

PMID- 24671415
TI  - Normal activation of discoidin domain receptor 1 mutants with disulfide cross
      links, insertions, or deletions in the extracellular juxtamembrane region:
      mechanistic implications.
AB  - The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases that
      are activated by collagen. DDR activation does not appear to occur by the common
      mechanism of ligand-induced receptor dimerization: the DDRs form stable
      noncovalent dimers in the absence of ligand, and ligand-induced
      autophosphorylation of cytoplasmic tyrosines is unusually slow and sustained.
      Here we sought to identify functionally important dimer contacts within the
      extracellular region of DDR1 by using cysteine-scanning mutagenesis. Cysteine
      substitutions close to the transmembrane domain resulted in receptors that formed
      covalent dimers with high efficiency, both in the absence and presence of
      collagen. Enforced covalent dimerization did not result in constitutive
      activation and did not affect the ability of collagen to induce receptor
      autophosphorylation. Cysteines farther away from the transmembrane domain were
      also cross-linked with high efficiency, but some of these mutants could no longer
      be activated. Furthermore, the extracellular juxtamembrane region of DDR1
      tolerated large deletions as well as insertions of flexible segments, with no
      adverse effect on activation. These findings indicate that the extracellular
      juxtamembrane region of DDR1 is exceptionally flexible and does not constrain the
      basal or ligand-activated state of the receptor. DDR1 transmembrane signaling
      thus appears to occur without conformational coupling through the juxtamembrane
      region, but requires specific receptor interactions farther away from the cell
      membrane. A plausible mechanism to explain these findings is signaling by DDR1
      clusters. 

PMID- 24671416
TI  - Structural characterization of heparin-induced glyceraldehyde-3-phosphate
      dehydrogenase protofibrils preventing alpha-synuclein oligomeric species
      toxicity.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme that
      has been associated with neurodegenerative diseases. GAPDH colocalizes with alpha
      synuclein in amyloid aggregates in post-mortem tissue of patients with sporadic
      Parkinson disease and promotes the formation of Lewy body-like inclusions in cell
      culture. In a previous work, we showed that glycosaminoglycan-induced GAPDH
      prefibrillar species accelerate the conversion of alpha-synuclein to fibrils.
      However, it remains to be determined whether the interplay among
      glycosaminoglycans, GAPDH, and alpha-synuclein has a role in pathological states.
      Here, we demonstrate that the toxic effect exerted by alpha-synuclein oligomers
      in dopaminergic cell culture is abolished in the presence of GAPDH prefibrillar
      species. Structural analysis of prefibrillar GAPDH performed by small angle x-ray
      scattering showed a particle compatible with a protofibril. This protofibril is
      shaped as a cylinder 22 nm long and a cross-section diameter of 12 nm. Using
      biocomputational techniques, we obtained the first all-atom model of the GAPDH
      protofibril, which was validated by cross-linking coupled to mass spectrometry
      experiments. Because GAPDH can be secreted outside the cell where
      glycosaminoglycans are present, it seems plausible that GAPDH protofibrils could
      be assembled in the extracellular space kidnapping alpha-synuclein toxic
      oligomers. Thus, the role of GAPDH protofibrils in neuronal proteostasis must be
      considered. The data reported here could open alternative ways in the development
      of therapeutic strategies against synucleinopathies like Parkinson disease. 

PMID- 24671417
TI  - Lysine 27 ubiquitination of the mitochondrial transport protein Miro is dependent
      on serine 65 of the Parkin ubiquitin ligase.
AB  - Mitochondrial transport plays an important role in matching mitochondrial
      distribution to localized energy production and calcium buffering requirements.
      Here, we demonstrate that Miro1, an outer mitochondrial membrane (OMM) protein
      crucial for the regulation of mitochondrial trafficking and distribution, is a
      substrate of the PINK1/Parkin mitochondrial quality control system in human
      dopaminergic neuroblastoma cells. Moreover, Miro1 turnover on damaged
      mitochondria is altered in Parkinson disease (PD) patient-derived fibroblasts
      containing a pathogenic mutation in the PARK2 gene (encoding Parkin). By
      analyzing the kinetics of Miro1 ubiquitination, we further demonstrate that
      mitochondrial damage triggers rapid (within minutes) and persistent Lys-27-type
      ubiquitination of Miro1 on the OMM, dependent on PINK1 and Parkin. Proteasomal
      degradation of Miro1 is then seen on a slower time scale, within 2-3 h of the
      onset of ubiquitination. We find Miro ubiquitination in dopaminergic
      neuroblastoma cells is independent of Miro1 phosphorylation at Ser-156 but is
      dependent on the recently identified Ser-65 residue within Parkin that is
      phosphorylated by PINK1. Interestingly, we find that Miro1 can stabilize phospho
      mutant versions of Parkin on the OMM, suggesting that Miro is also part of a
      Parkin receptor complex. Moreover, we demonstrate that Ser-65 in Parkin is
      critical for regulating Miro levels upon mitochondrial damage in rodent cortical
      neurons. Our results provide new insights into the ubiquitination-dependent
      regulation of the Miro-mediated mitochondrial transport machinery by PINK1/Parkin
      and also suggest that disruption of this regulation may be implicated in
      Parkinson disease pathogenesis. 

PMID- 24671418
TI  - Activation-induced tumor necrosis factor receptor-associated factor 3 (Traf3)
      alternative splicing controls the noncanonical nuclear factor kappaB pathway and
      chemokine expression in human T cells.
AB  - The noncanonical nuclear factor kappaB (ncNFkappaB) pathway regulates the
      expression of chemokines required for secondary lymphoid organ formation and thus
      plays a pivotal role in adaptive immunity. Whereas ncNFkappaB signaling has been
      well described in stromal cells and B cells, its role and regulation in T cells
      remain largely unexplored. ncNFkappaB activity critically depends on the upstream
      NFkappaB-inducing kinase (NIK). NIK expression is negatively regulated by the
      full-length isoform of TNF receptor-associated factor 3 (Traf3) as formation of a
      NIK-Traf3-Traf2 complex targets NIK for degradation. Here we show that T cell
      specific and activation-dependent alternative splicing generates a Traf3 isoform
      lacking exon 8 (Traf3DE8) that, in contrast to the full-length protein, activates
      ncNFkappaB signaling. Traf3DE8 disrupts the NIK-Traf3-Traf2 complex and allows
      accumulation of NIK to initiate ncNFkappaB signaling in activated T cells.
      ncNFkappaB activity results in expression of several chemokines, among them B
      cell chemoattractant (CxCL13), both in a model T cell line and in primary human
      CD4(+) T cells. Because CxCL13 plays an important role in B cell migration and
      activation, our data suggest an involvement and provide a mechanistic basis for
      Traf3 alternative splicing and ncNFkappaB activation in contributing to T cell
      dependent adaptive immunity. 

PMID- 24671419
TI  - Human cytochrome P450 17A1 conformational selection: modulation by ligand and
      cytochrome b5.
AB  - Crystallographic studies of different membrane cytochrome P450 enzymes have
      provided examples of distinct structural conformations, suggesting protein
      flexibility. It has been speculated that conformational selection is an integral
      component of substrate recognition and access, but direct evidence of such
      substate interconversion has thus far remained elusive. In the current study,
      solution NMR revealed multiple and exchanging backbone conformations for certain
      structural features of the human steroidogenic cytochrome P450 17A1 (CYP17A1).
      This bifunctional enzyme is responsible for pregnenolone C17 hydroxylation,
      followed by a 17,20-lyase reaction to produce dehydroepiandrosterone, the key
      intermediate in human synthesis of androgen and estrogen sex steroids. The
      distribution of CYP17A1 conformational states was influenced by temperature,
      binding of these two substrates, and binding of the soluble domain of cytochrome
      b5 (b5). Notably, titration of b5 to CYP17A1.pregnenolone induced a set of
      conformational states closely resembling those of CYP17A1.17alpha
      hydroxypregnenolone without b5, providing structural evidence consistent with the
      reported ability of b5 to selectively enhance 17,20-lyase activity. Solution NMR
      thus revealed a set of conformations likely to modulate human steroidogenesis by
      CYP17A1, demonstrating that this approach has the potential to make similar
      contributions to understanding the functions of other membrane P450 enzymes
      involved in drug metabolism and disease states. 

PMID- 24671421
TI  - Hierarchical functional specificity of cytosolic heat shock protein 70 (Hsp70)
      nucleotide exchange factors in yeast.
AB  - Heat shock protein 70 (Hsp70) molecular chaperones play critical roles in protein
      homeostasis. In the budding yeast Saccharomyces cerevisiae, cytosolic Hsp70
      interacts with up to three types of nucleotide exchange factors (NEFs) homologous
      to human counterparts: Sse1/Sse2 (Heat shock protein 110 (Hsp110)), Fes1
      (HspBP1), and Snl1 (Bag-1). All three NEFs stimulate ADP release; however, it is
      unclear why multiple distinct families have been maintained throughout eukaryotic
      evolution. In this study we investigate NEF roles in Hsp70 cell biology using an
      isogenic combinatorial collection of NEF deletion mutants. Utilizing well
      characterized model substrates, we find that Sse1 participates in most Hsp70
      mediated processes and is of particular importance in protein biogenesis and
      degradation, whereas Fes1 contributes to a minimal extent. Surprisingly,
      disaggregation and resolubilization of thermally denatured firefly luciferase
      occurred independently of NEF activity. Simultaneous deletion of SSE1 and FES1
      resulted in constitutive activation of heat shock protein expression mediated by
      the transcription factor Hsf1, suggesting that these two factors are important
      for modulating stress response. Fes1 was found to interact in vivo preferentially
      with the Ssa family of cytosolic Hsp70 and not the co-translational Ssb homolog,
      consistent with the lack of cold sensitivity and protein biogenesis phenotypes
      for fes1Delta cells. No significant consequence could be attributed to deletion
      of the minor Hsp110 SSE2 or the Bag homolog SNL1. Together, these lines of
      investigation provide a comparative analysis of NEF function in yeast that
      implies Hsp110 is the principal NEF for cytosolic Hsp70, making it an ideal
      candidate for therapeutic intervention in human protein folding disorders. 

PMID- 24671423
TI  - Mr Waxman went to Washington: congressman an architect of health laws for 4
      decades.

PMID- 24671420
TI  - Myelin basic protein cleaves cell adhesion molecule L1 and promotes
      neuritogenesis and cell survival.
AB  - The cell adhesion molecule L1 is a Lewis(x)-carrying glycoprotein that plays
      important roles in the developing and adult nervous system. Here we show that
      myelin basic protein (MBP) binds to L1 in a Lewis(x)-dependent manner.
      Furthermore, we demonstrate that MBP is released by murine cerebellar neurons as
      a sumoylated dynamin-containing protein upon L1 stimulation and that this MBP
      cleaves L1 as a serine protease in the L1 extracellular domain at Arg(687)
      yielding a transmembrane fragment that promotes neurite outgrowth and neuronal
      survival in cell culture. L1-induced neurite outgrowth and neuronal survival are
      reduced in MBP-deficient cerebellar neurons and in wild-type cerebellar neurons
      in the presence of an MBP antibody or L1 peptide containing the MBP cleavage
      site. Genetic ablation of MBP in shiverer mice and mutagenesis of the
      proteolytically active site in MBP or of the MBP cleavage site within L1 as well
      as serine protease inhibitors and an L1 peptide containing the MBP cleavage site
      abolish generation of the L1 fragment. Our findings provide evidence for novel
      functions of MBP in the nervous system. 

PMID- 24671422
TI  - Structural similarity between defense peptide from wheat and scorpion neurotoxin
      permits rational functional design.
AB  - In this study, we present the spatial structure of the wheat antimicrobial
      peptide (AMP) Tk-AMP-X2 studied using NMR spectroscopy. This peptide was found to
      adopt a disulfide-stabilized alpha-helical hairpin fold and therefore belongs to
      the alpha-hairpinin family of plant defense peptides. Based on Tk-AMP-X2
      structural similarity to cone snail and scorpion potassium channel blockers, a
      mutant molecule, Tk-hefu, was engineered by incorporating the functionally
      important residues from kappa-hefutoxin 1 onto the Tk-AMP-X2 scaffold. The
      designed peptide contained the so-called essential dyad of amino acid residues
      significant for channel-blocking activity. Electrophysiological studies showed
      that although the parent peptide Tk-AMP-X2 did not present any activity against
      potassium channels, Tk-hefu blocked Kv1.3 channels with similar potency (IC50 ~
      35 MUm) to kappa-hefutoxin 1 (IC50 ~ 40 MUm). We conclude that alpha-hairpinins
      are attractive in their simplicity as structural templates, which may be used for
      functional engineering and drug design. 

PMID- 24671425
TI  - A paper based self-pumping and self-breathing fuel cell using pencil stroked
      graphite electrodes.
AB  - We develop a paper based fuel cell in which fluids flow through a capillary
      transport mechanism. The pencil stroked graphite electrodes take oxygen from
      quiescent air. This simple and efficient paper fuel cell can generate energy to
      the tune of 32 mW cm(-2) over a prolonged duration of around 1000 minutes, and
      with the consumption of a very low volume of formic acid as fuel (~1 mL). 

PMID- 24671424
TI  - A high-throughput device for size based separation of C. elegans developmental
      stages.
AB  - Caenorhabditis elegans is a widely used model organism to study development,
      aging and behavior. Many of these biological studies require staging a large
      number of worms to assay a synchronized population of animals. Conventional
      synchronization techniques such as manual picking, gravity stratification and
      chemical bleaching are labor-intensive and could perturb animals' physiology.
      Thus, there is a need for a simple inexpensive technology to sort a mixed
      population of worms based on their developmental stages with minimal
      perturbation. Here we demonstrate a simple but accurate and high-throughput
      technique to sort based on animal size, which correlates well with developmental
      stages. The device consists of an array of geometrically optimized pillars that
      act as a sieve to allow worms of specific sizes to rapidly move through. With
      optimized chamber heights, pillar spacing and driving pressures, these binary
      separation devices are capable of independently separating a mixture of worms at
      two different stages at average efficiency of around 95%, and throughput of
      hundreds of worms per minute. In addition, when four devices are used
      sequentially, we demonstrate the ability to stratify a mixture of worms of all
      developmental stages with >85% overall efficiency. 

PMID- 24671426
TI  - MAGE-A3 with cell-penetrating domain as an efficient therapeutic cancer vaccine.
AB  - IMPORTANCE: In conjunction with chemotherapy, immunotherapy with dendritic cells
      (DCs) may eliminate minimal disease burden by generating cytotoxic T lymphocytes.
      Enhanced cytosolic bioavailability of tumor-specific antigens improves access to
      human leukocyte antigen (HLA) class I molecules for more efficient cytotoxic T
      lymphocyte generation. Various cell-penetrating domains (CPDs) are known to ferry
      covalently linked heterologous antigens to the intracellular compartment by
      traversing the plasma membrane. OBJECTIVE: To determine whether generating
      melanoma antigen family A, 3 (MAGE-A3), a tumor-specific cancer-testis antigen,
      as a fusion protein with CPD will enhance the cytosolic bioavailability of MAGE
      A3. DESIGN: MAGE-A3 was amplified by polymerase chain reaction using
      complementary DNA from renal tissue and cloned in frame with a CPD (YARKARRQARR)
      at the amino-terminal end and hexahistidine at the carboxy-terminal end to
      generate CPD-MAGE-A3 in a pQE-70 expression vector. Cultures were grown in
      Escherichia coli BL21 Star (DE3-pLysS) cells followed by nickel-nitrilotriacetic
      acid affinity purification of recombinant proteins. MAIN OUTCOMES AND MEASURES:
      Measurement of DC membrane penetration of CPD-MAGE-A3 vs MAGE-A3 and
      determination of the effect of CPD-MAGE-A3 pulsing on DC phenotypic expression of
      cell-surface antigens. RESULTS: Media composition and isopropyl-d
      thiogalactosidase induction were optimized to achieve high levels of protein
      expression followed by purification. Western blot analysis with MAGE-A3
      antibodies recognized both MAGE-A3 and CPD-MAGE-A3 proteins, while CPD antibodies
      recognized only CPD-MAGE-A3. Purified CPD-MAGE-A3 exhibited more efficient DC
      membrane penetration than did MAGE-A3 alone as confirmed by immunofluorescence
      analysis. High-level expression of several unique DC markers (CD80, CD83, CD86,
      and HLA-DR) by flow cytometry was consistent with a mature DC phenotype,
      indicating that pulsing with CPD-MAGE-A3 did not alter specific cell-surface
      antigens required for T-cell activation. CONCLUSIONS AND RELEVANCE: We have
      demonstrated for the first time, to our knowledge, that cloning and purification
      of MAGE-A3 with CPD enhances its cytosolic bioavailability in DCs without
      altering cell-surface antigens, potentially making it a more potent therapeutic
      cancer vaccine compared with existing MAGE-A3 protein and peptide vaccines.

PMID- 24671427
TI  - Demographic stochasticity and evolution of dispersion II: spatially inhomogeneous
      environments.
AB  - Demographic stochasticity, the random fluctuations arising from the intrinsic
      discreteness of populations and the uncertainty of individual birth and death
      events, is an essential feature of population dynamics. Nevertheless theoretical
      investigations often neglect this naturally occurring noise due to the
      mathematical complexity of stochastic models. This paper reports the results of
      analytical and computational investigations of models of competitive population
      dynamics, specifically the competition between species in heterogeneous
      environments with different phenotypes of dispersal, fully accounting for
      demographic stochasticity. A novel asymptotic approximation is introduced and
      applied to derive remarkably simple analytical forms for key statistical
      quantities describing the populations' dynamical evolution. These formulas
      characterize the selection processes that determine which (if either) competitor
      has an evolutionary advantage. The theory is verified by large-scale numerical
      simulations. We discover that the fluctuations can (1) break dynamical
      degeneracies, (2) support polymorphism that does not exist in deterministic
      models, (3) reverse the direction of the weak selection and cause shifts in
      selection regimes, and (4) allow for the emergence of evolutionarily stable
      dispersal rates. Dynamical mechanisms and time scales of the fluctuation-induced
      phenomena are identified within the theoretical approach. 

PMID- 24671428
TI  - Approximation of epidemic models by diffusion processes and their statistical
      inference.
AB  - Multidimensional continuous-time Markov jump processes [Formula: see text] on
      [Formula: see text] form a usual set-up for modeling [Formula: see text]-like
      epidemics. However, when facing incomplete epidemic data, inference based on
      [Formula: see text] is not easy to be achieved. Here, we start building a new
      framework for the estimation of key parameters of epidemic models based on
      statistics of diffusion processes approximating [Formula: see text]. First,
      previous results on the approximation of density-dependent [Formula: see text]
      like models by diffusion processes with small diffusion coefficient [Formula: see
      text], where [Formula: see text] is the population size, are generalized to non
      autonomous systems. Second, our previous inference results on discretely observed
      diffusion processes with small diffusion coefficient are extended to time
      dependent diffusions. Consistent and asymptotically Gaussian estimates are
      obtained for a fixed number [Formula: see text] of observations, which
      corresponds to the epidemic context, and for [Formula: see text]. A correction
      term, which yields better estimates non asymptotically, is also included.
      Finally, performances and robustness of our estimators with respect to various
      parameters such as [Formula: see text] (the basic reproduction number), [Formula:
      see text], [Formula: see text] are investigated on simulations. Two models,
      [Formula: see text] and [Formula: see text], corresponding to single and
      recurrent outbreaks, respectively, are used to simulate data. The findings
      indicate that our estimators have good asymptotic properties and behave
      noticeably well for realistic numbers of observations and population sizes. This
      study lays the foundations of a generic inference method currently under
      extension to incompletely observed epidemic data. Indeed, contrary to the
      majority of current inference techniques for partially observed processes, which
      necessitates computer intensive simulations, our method being mostly an
      analytical approach requires only the classical optimization steps. 

PMID- 24671430
TI  - Cross-diffusion-driven instability for reaction-diffusion systems: analysis and
      simulations.
AB  - By introducing linear cross-diffusion for a two-component reaction-diffusion
      system with activator-depleted reaction kinetics (Gierer and Meinhardt,
      Kybernetik 12:30-39, 1972; Prigogine and Lefever, J Chem Phys 48:1695-1700, 1968;
      Schnakenberg, J Theor Biol 81:389-400, 1979), we derive cross-diffusion-driven
      instability conditions and show that they are a generalisation of the classical
      diffusion-driven instability conditions in the absence of cross-diffusion. Our
      most revealing result is that, in contrast to the classical reaction-diffusion
      systems without cross-diffusion, it is no longer necessary to enforce that one of
      the species diffuse much faster than the other. Furthermore, it is no longer
      necessary to have an activator-inhibitor mechanism as premises for pattern
      formation, activator-activator, inhibitor-inhibitor reaction kinetics as well as
      short-range inhibition and long-range activation all have the potential of giving
      rise to cross-diffusion-driven instability. To support our theoretical findings,
      we compute cross-diffusion induced parameter spaces and demonstrate similarities
      and differences to those obtained using standard reaction-diffusion theory.
      Finite element numerical simulations on planary square domains are presented to
      back-up theoretical predictions. For the numerical simulations presented, we
      choose parameter values from and outside the classical Turing diffusively-driven
      instability space; outside, these are chosen to belong to cross-diffusively
      driven instability parameter spaces. Our numerical experiments validate our
      theoretical predictions that parameter spaces induced by cross-diffusion in both
      the [Formula: see text] and [Formula: see text] components of the reaction
      diffusion system are substantially larger and different from those without cross
      diffusion. Furthermore, the parameter spaces without cross-diffusion are sub
      spaces of the cross-diffusion induced parameter spaces. Our results allow
      experimentalists to have a wider range of parameter spaces from which to select
      reaction kinetic parameter values that will give rise to spatial patterning in
      the presence of cross-diffusion. 

PMID- 24671429
TI  - Computational haemodynamics in stenotic internal jugular veins.
AB  - An association of stenotic internal jugular veins (IJVs) to anomalous cerebral
      venous hemodynamics and Multiple Sclerosis has been recently hypothesized. In
      this work, we set up a computational framework to assess the relevance of IJV
      stenoses through numerical simulation, combining medical imaging, patient
      specific data and a mathematical model for venous occlusions. Coupling a three
      dimensional description of blood flow in IJVs with a reduced one-dimensional
      model for major intracranial veins, we are able to model different anatomical
      configurations, an aspect of importance to understand the impact of IJV stenosis
      in intracranial venous haemodynamics. We investigate several stenotic
      configurations in a physiologic patient-specific regime, quantifying the effect
      of the stenosis in terms of venous pressure increase and wall shear stress
      patterns. Simulation results are in qualitative agreement with reported pressure
      anomalies in pathological cases. Moreover, they demonstrate the potential of the
      proposed multiscale framework for individual-based studies and computer-aided
      diagnosis. 

PMID- 24671432
TI  - Isomorphous substitution of divalent metal ions in layered double hydroxides
      through a soft chemical hydrothermal reaction.
AB  - We have successfully incorporated Co(2+) ions into layered double hydroxides
      (LDHs) comprising Mg and Al hydroxides via isomorphous substitution utilizing a
      soft chemical hydrothermal reaction. The inductively coupled plasma-atomic
      emission spectroscopy (ICP-AES) analysis showed that the incorporation of Co(2+)
      into an LDH was highly dependent on the dissolution of Mg(2+). The X-ray
      diffraction (XRD) patterns showed that the crystalline phase, as well as the
      crystallinity of pristine LDH, was well preserved without the evolution of
      impurities during the substitution reaction. It was notable that the size (~250
      nm) and hexagonal plate-like morphology of LDHs did not change significantly upon
      Co(2+) substitution. Transmission electron microscopy-energy dispersive
      spectroscopy (TEM-EDS) exhibited homogeneous distribution of Co(2+) in the LDH
      particles obtained by this substitution reaction. Solid-state UV-vis and X-ray
      absorption spectroscopy (XAS) verified that the incorporated Co(2+) ions were
      well stabilized in the octahedral sites of an LDH, which were formerly occupied
      by Mg(2+) ions.

PMID- 24671433
TI  - Neuropsychological care and rehabilitation of cancer patients with chemobrain:
      strategies for evaluation and intervention development.
AB  - Malignant tumors and their various treatments such as chemotherapy, radiotherapy
      and hormonal therapy can deleteriously affect a large number of cancer patients
      and survivors on multiple dimensions of psychosocial and neurocognitive
      functioning. Oncology researchers and clinicians are increasingly cognizant of
      the negative effects of cancer and its treatments on the brain and its mental
      processes and cognitive outcomes. Nevertheless, effective interventions to treat
      cancer and treatment-related neurocognitive dysfunction (CRND), also known as
      chemobrain, are still lacking. The paucity of data on effective treatments for
      CRND is due, at least partly, to difficulties understanding its etiology, and a
      lack of reliable methods for assessing its presence and severity. This paper
      provides an overview of the incidence, etiology, and magnitude of CRND, and
      discusses the plausible contributions of psychological, motor function, and
      linguistic and behavioral complications to CRND. Strategies for reliable
      neuropsychological screening and assessment, and development and testing of
      effective ways to mitigate CRND are also discussed. 

PMID- 24671434
TI  - Effect of dance on cancer-related fatigue and quality of life.
AB  - PURPOSE: Cancer-related fatigue is a multidimensional symptom with an
      underestimated prevalence and severity in cancer patients. The aim of the study
      was to evaluate the effect of dance as a holistic sportive activity in cancer
      patients under active anticancer treatment with fatigue as endpoint. PATIENTS AND
      METHODS: Forty patients under active anticancer treatment (adjuvant (25),
      palliative (11) or neoadjuvant (4)) with moderate or severe fatigue (>= 4 on the
      visual analogue scale) were investigated in two groups for severity of fatigue
      (visual analogue scale, Functional Assessment of Chronic Illness Therapy: Fatigue
      questionnaire), quality of life (European Organization for Research and Treatment
      of Cancer, Quality of Life Questionnaire) and physical performance (6-minute walk
      test) before and after the study period--group A (n = 20): intervention (10 dance
      classes in 5 weeks in addition to counselling) and group B (n = 20): control (no
      dance, standard of care, counselling). RESULTS: We found significant improvements
      for cancer-related fatigue in the intervention group (baseline mean +/- SD 5.95
      +/- 1.701, end-of-study mean 3.8 +/- 1.542, p = 0.001, reduction of 36 %)
      compared to the control group (baseline mean 4.95 +/- 0.999, end-of-study mean
      unchanged at 5.0 +/- 1.556, p = 0.887); as well as for emotional and social
      functioning scales and physical performance (p < 0.05). CONCLUSION: Dance might
      be an appropriate, effective approach for treatment of cancer-related fatigue.

PMID- 24671436
TI  - Locally stable diamond colloidal crystal formed in a cholesteric liquid crystal.
AB  - We use a Landau de Gennes free energy approach to model a diamond colloidal
      crystal immersed in a cholesteric liquid crystal. The pitch in our cholesteric is
      chosen in order to give rise to the most energetically favourable colloid-defect
      structure, commensurate with the diamond lattice. This structure corresponds to
      defect lines travelling along symmetry axes in the diamond crystal. By adding
      noise to the liquid crystal phase we are able to measure the phonon spectrum of
      our colloidal crystal, which we find to be consistent with a locally stable
      configuration. Therefore, although it may not correspond to the global minimum
      energy structure, once formed our diamond lattice should be stable against
      thermal fluctuations. 

PMID- 24671435
TI  - Referral practices of pediatric oncologists to specialized palliative care.
AB  - PURPOSE: The aims of this study are to describe the attitudes and referral
      practices of pediatric oncologists (POs) to specialized palliative care (SPC),
      and to compare them with those of adult oncologists (AOs). METHODS: Canadian
      members of the American Society of Pediatric Hematology/Oncology (ASPHO),
      Canadian Association of Medical Oncologists (CAMO), Canadian Association of
      Radiation Oncologists (CARO), and the Canadian Society of Surgical Oncology
      (CSSO) participated in an anonymous survey assessing SPC referral practices.
      RESULTS: The response rate was 70 % (646/921), 52 % (43/82) for ASPHO members; 5
      CARO members self-identified as POs, for a total of 48 POs and 595 AOs. Ninety
      six percent of POs had access to inpatient SPC consultation services (vs. 48 %
      AOs), 31 % to a PCU (vs. 82 % AOs), and 27 % to an outpatient SPC clinic (vs. 73
      % AOs). POs more often stated their SPC services accepted patients on
      chemotherapy than AOs (64 vs. 37 %, p = 0.0004). POs were less likely to refer
      only after chemotherapy had been stopped (13 vs. 29 % for AOs) and more likely to
      state that ideally referral should occur at the diagnosis of cancer/incurable
      cancer (73 vs. 43 %). POs were more likely to agree they would refer earlier if
      palliative care were renamed "supportive care" (58 vs. 33 %, p < 0.0001), that
      palliative care adds too many providers (17 vs. 7 %, p = 0.002), and that
      palliative care was perceived negatively by their patients (60 vs. 43 %, p =
      0.02). CONCLUSIONS: Although POs acknowledge the importance of early referral to
      SPC for children with cancer, there remain resource and attitudinal barriers to
      overcome in this regard.

PMID- 24671438
TI  - Prevalence of idiopathic cuneate gyrus herniation based on emergency room CT
      examinations.
AB  - Idiopathic brain herniation caused by a focal dural defect can be confused for a
      mass or post-traumatic herniation. The prevalence of idiopathic brain herniation
      has never been described. We sought to ascertain the prevalence of idiopathic
      cuneate gyrus herniation in a general emergency room (ER) population on computed
      tomography (CT) imaging. The purpose of this study is to elucidate cuneate gyrus
      herniation and differentiate it from other pathologic conditions such as mass or
      traumatic herniation and to provide its anatomical prevalence in an ER
      population. Consecutive emergency room CT scans of the brain were evaluated
      prospectively for cuneate gyrus herniation over a 1 year period by a
      neuroradiologist. Of 1,500 brain CT scans evaluated, 11 patients demonstrated
      idiopathic cuneus gyrus herniation. The prevalence was 0.73 %. CT manifestations
      are normal brain tissue herniating into the superior cerebellar cistern.
      Idiopathic brain herniation can be mistaken for a pathologic process. We found
      the prevalence of one such idiopathic brain herniation, involving the cuneus
      gyrus, to be exceedingly rare. CT imaging demonstrates normal brain tissue
      herniating beyond the dural boundary.

PMID- 24671437
TI  - Bidirectional effect of Wnt signaling antagonist DKK1 on the modulation of
      anthrax toxin uptake.
AB  - LRP6, a co-receptor for the morphogen Wnt, aids endocytosis of anthrax complexes.
      Here we report that Dickkopf1 (DKK1) protein, a secreted LRP6 ligand and
      antagonist, is also a modulator of anthrax toxin sensitivity. shRNA-mediated gene
      silencing or TALEN-mediated gene knockout of DKK1 reduced sensitivity of cells to
      PA-dependent hybrid toxins. However, unlike the solely inhibitory effect on Wnt
      signaling, the effects of DKK1 overexpression on anthrax toxicity were
      bidirectional, depending on its endogenous expression and cell context.
      Fluorescence microscopy and biochemical analyses showed that DKK1 facilitates
      internalization of anthrax toxins and their receptors, an event mediated by DKK1
      LRP6-Kremen2 complex. Monoclonal antibodies against DKK1 provided dose-dependent
      protection to macrophages from killing by anthrax lethal toxin (LT). Our
      discovery that DKK1 forms ternary structure with LRP6 and Kremen2 in promoting PA
      mediated toxin internalization provides a paradigm for bacterial exploitation of
      mechanisms that host cells use to internalize signaling proteins. 

PMID- 24671439
TI  - Solid state chemistry of nitrogen oxides--part II: surface consumption of NO2.
AB  - Nitrogen oxides are considered to be important astrochemical precursors of
      complex species and prebiotics. However, apart from the hydrogenation of solid NO
      that leads to the surface formation of hydroxylamine, little is known about the
      full solid state reaction network involving both nitrogen and oxygen. Our study
      is divided into two papers, hereby called Part I and Part II. In the accompanying
      paper, we investigate the surface reactions NO + O/O2/O3 and NO + N with a focus
      on the formation of NO2 ice. Here, we complement this study by measurements of
      the surface destruction of solid NO2, e.g., NO2 + H/O/N. Experiments are
      performed in two separate ultra-high vacuum setups and therefore under different
      experimental conditions to better constrain the experimental results. Surface
      reaction products are monitored by means of Fourier Transform Reflection
      Absorption Infrared Spectroscopy (FT-RAIRS) and Temperature Programmed Desorption
      (TPD) techniques using mass spectrometry. The surface destruction of solid NO2
      leads to the formation of a series of nitrogen oxides such as NO, N2O, N2O3, and
      N2O4 as well as HNO, NH2OH, and H2O. When NO2 is mixed with an interstellar more
      relevant apolar (i.e., CO) ice, solid CO2 and HCOOH are also formed due to
      interactions between different reaction routes. The astrophysical implications of
      the full nitrogen and oxygen reaction network derived from Parts I and II are
      discussed. 

PMID- 24671440
TI  - Genetic diversity of Microcystis cyanophages in two different freshwater
      environments.
AB  - Bacteriophages rapidly diversify their genes through co-evolution with their
      hosts. We hypothesize that gene diversification of phages leads to locality in
      phages genome. To test this hypothesis, we investigated the genetic diversity and
      composition of Microcystis cyanophages using 104 sequences of Ma-LMM01-type
      cyanophages from two geographically distant sampling sites. The intergenetic
      region between the ribonucleotide reductase genes nrdA and nrdB was used as the
      genetic marker. This region contains the host-derived auxiliary metabolic genes
      nblA, an unknown function gene g04, and RNA ligase gene g03. The sequences
      obtained were conserved in the Ma-LMM01 gene order and contents. Although the
      genetic diversity of the sequences was high, it varied by gene. The genetic
      diversity of nblA was the lowest, suggesting that nblA is a highly significant
      gene that does not allow mutation. In contrast, g03 sequences had many point
      mutations. RNA ligase is involved in the counter-host's phage defense mechanism,
      suggesting that phage defense also plays an important role for rapid gene
      diversification. The maximum parsimony network and phylogenic analysis showed the
      sequences from the two sampling sites were distinct. These findings suggest Ma
      LMM01-type phages rapidly diversify their genomes through co-evolution with hosts
      in each location and eventually provided locality of their genomes.

PMID- 24671441
TI  - Health-Promoting Verses as mentioned in the Holy Quran.
AB  - The Quran is regarded as both the spiritual and behavioral guidance for all
      Muslims. This narrative study was designed at examining relevant health-promoting
      verses in the Quran and to identify the chapters and verses where keywords and
      phrases are mentioned relevant to health promotion and behavior. Twenty-eight
      verses were identified, with a focus on diet and nutrition, personal hygiene,
      alcohol abstention, and the importance of a healthy lifestyle. These results
      suggest that the Quran could serve as an influential medium for culturally
      competent public health practitioners in diverse populations, particularly in
      Muslim communities, for improving and maintaining healthy behaviors. 

PMID- 24671442
TI  - Tuberculous nephritis accompanying neuromyelitis optica: causal or coincidental
      association?

PMID- 24671443
TI  - Microfluidic liquid jet system with compatibility for atmospheric and high-vacuum
      conditions.
AB  - We present microfluidic chip based devices that produce liquid jets with
      micrometer diameters while operating at very low flow rates. The chip production
      is based on established soft-lithographical techniques employing a three-layer
      design protocol. This allows the exact, controlled and reproducible design of
      critical parts such as nozzles and the production of nozzle arrays. The
      microfluidic chips reproducibly generate liquid jets exiting at perfect right
      angles with diameters between 20 MUm and 2 MUm, and under special circumstances,
      even down to 0.9 MUm. Jet diameter, jet length, and the domain of the
      jetting/dripping instability can be predicted and controlled based on the theory
      for liquid jets in the plate-orifice configuration described by Ganan-Calvo et
      al. Additionally, conditions under which the device produces highly reproducible
      monodisperse droplets at exact and predictable rates can be achieved. The devices
      operate under atmospheric and under vacuum conditions making them highly relevant
      for a wide range of applications, for example, for free-electron lasers. Further,
      the straightforward integration of additional features such as a jet-in-jet is
      demonstrated. This device design has the potential to integrate more features
      based on established microfluidic components and may become a standard device for
      small liquid jet production. 

PMID- 24671444
TI  - In reply to detection of skeletal muscle metastases at the initial staging of
      lung cancer: a retrospective case series.

PMID- 24671445
TI  - Preparation of RHgCl via transmetalation of (8-quinolyl)SnMe3 and redistribution
      to R2Hg (R = 8-quinolyl): a highly distorted diorganomercury(II) with 84 degree C
      Hg-C angle.
AB  - Transmetalation occurs upon addition of HgCl2 to (8-quinolyl)SnMe3 to yield (8
      quinolyl)HgCl. The molecule features a frustrated Hg-N Lewis pair; however the
      mercury(II) center showed low affinity for sulfur Lewis bases, S8 or thiophene.
      In the presence of NH4SCN, ligand redistribution led to R2Hg. The molecule was
      found as linear or bent polymorphs, depending on the solvent of
      recrystallization. The geometry about Hg(II) in the bent polymorph is distorted
      trigonal prismatic that features a C-Hg-C angle of 84 degrees , weak
      intramolecular Hg-N contacts, and two intermolecular eta(2)-quinoline contacts in
      which the neighboring R2Hg molecule participates as a bis-eta(2)-bidentate
      ligand.

PMID- 24671446
TI  - Generating electric fields in PDMS microfluidic devices with salt water
      electrodes.
AB  - Droplet merging and sorting in microfluidic devices usually rely on electric
      fields generated by solid metal electrodes. We show that simpler and more
      reliable salt water electrodes, despite their lower conductivity, can perform the
      same droplet manipulations at the same voltages. 

PMID- 24671447
TI  - Cartilage nominal strain correlates with shear modulus and glycosaminoglycans
      content in meniscectomized joints.
AB  - Postmeniscectomy osteoarthritis (OA) is hypothesized to be the consequence of
      abnormal mechanical conditions, but the relationship between postsurgical
      alterations in articular cartilage strain and in vivo biomechanical/biochemical
      changes in articular cartilage is unclear. We hypothesized that spatial
      variations in cartilage nominal strain (percentile thickness change) would
      correlate with previously reported in vivo articular cartilage property changes
      following meniscectomy. Cadevaric sheep knees were loaded in cyclic compression
      which was previously developed to mimic normal sheep gait, while a 4.7 T magnetic
      resonance imaging (MRI) imaged the whole joint. 3D cartilage strain maps were
      compared with in vivo sheep studies that described postmeniscectomy changes in
      shear modulus, phase lag, proteoglycan content and collagen organization/content
      in the articular cartilage. The area of articular cartilage experiencing high
      (overloaded) and low (underloaded) strain was significantly increased in the
      meniscectomized tibial compartment by 10% and 25%, respectively, while no
      significant changes were found in the nonmeniscectomized compartment. The
      overloaded and underloaded regions of articular cartilage in our in vitro
      specimens correlated with regions of in vivo shear modulus reduction.
      Glycosaminoglycans (GAG) content only increased at the underloaded articular
      cartilage but decreased at the overloaded articular cartilage. No significant
      correlation was found in phase lag and collagen organization/content changes with
      the strain variation. Comparisons between postsurgical nominal strain and in vivo
      cartilage property changes suggest that both overloading and underloading after
      meniscectomy may directly damage the cartilage matrix stiffness (shear modulus).
      Disruption of superficial cartilage by overloading might be responsible for the
      proteoglycan (GAG) loss in the early stage of postmeniscectomy OA. 

PMID- 24671448
TI  - Surgeon-modified fenestrated endograft to treat ruptured juxtarenal aneurysm.
AB  - IMPORTANCE: No endovascular devices are commercially available in the United
      States to treat high-surgical risk patients with aneurysms extending to visceral
      arteries. Treatment options are even further limited for symptomatic patients in
      need of urgent treatment. OBJECTIVE: To describe a successful urgent endovascular
      repair of a juxtarenal abdominal aortic aneurysm with contained rupture. DESIGN,
      SETTING, AND PARTICIPANTS: A hybrid suite using a surgeon-modified fenestrated
      endovascular graft and advanced 3-dimensional imaging workstation. The patient
      was an 82-year-old veteran taking clopidogrel and aspirin for coronary stents
      with significant cardiopulmonary comorbidities including multiple prior abdominal
      surgeries and a single functional left kidney. INTERVENTION: Surgeon-modified
      fenestrated endovascular aortic aneurysm repair. MAIN OUTCOMES AND MEASURES:
      Clinical, laboratory, and radiographic improvement. RESULTS: The patient was
      discharged 5 days after an uneventful postoperative course. On short-term follow
      up, the patient had an early return to his baseline functional status. The
      excluded aneurysm sac shrank with patent visceral branches and there was an
      absence of endoleak on 3-month and 6-month surveillance computed tomography
      angiography. CONCLUSIONS AND RELEVANCE: Surgeon-modified fenestrated stent grafts
      may be a viable option for selected high-surgical risk patients with symptomatic
      complex abdominal aortic aneurysms.

PMID- 24671449
TI  - Effective medium theory for drag-reducing micro-patterned surfaces in turbulent
      flows.
AB  - Many studies in the last decade have revealed that patterns at the microscale can
      reduce skin drag. Yet, the mechanisms and parameters that control drag reduction,
      e.g. Reynolds number and pattern geometry, are still unclear. We propose an
      effective medium representation of the micro-features, that treats the latter as
      a porous medium, and provides a framework to model turbulent flow over patterned
      surfaces. Our key result is a closed-form expression for the skin friction
      coefficient in terms of frictional Reynolds (or Karman) number in turbulent
      regime, the viscosity ratio between the fluid in and above the features, and
      their geometrical properties. We apply the proposed model to turbulent flows over
      superhydrophobic ridged surfaces. The model predictions agree with laboratory
      experiments for Reynolds numbers ranging from 3000 to 10000. 

PMID- 24671451
TI  - Crohn's recurrence after intestinal resection and anastomosis.

PMID- 24671452
TI  - Downregulating sCLU enhances the sensitivity of hepatocellular carcinoma cells to
      gemcitabine by activating the intrinsic apoptosis pathway.
AB  - PURPOSE: The purpose of this study was to investigate whether the therapeutic
      activity of gemcitabine (GCB) in hepatocellular carcinoma (HCC) could be
      increased by the down-regulation of secretory clusterin (sCLU), a glycoprotein
      that is considered to play a cytoprotective role in the resistance to
      chemotherapy. METHODS: The expression of sCLU was detected in HCC tumor tissues
      and cell lines. A cell viability and apoptosis assay were performed in parental
      HCC cells or the same cells transfected with sCLU shRNA and treated with or
      without GCB. The potential downstream pathways were investigated using the Human
      Apoptosis RT(2) ProfilerTM PCR Array. RESULTS: The expression levels of sCLU in
      HCC tissues were significantly higher than in adjacent non-tumor liver tissues
      and were associated with the histological grade and transarterial
      chemoembolization. sCLU overexpression was also found in three HCC cell lines and
      hepatocytes. The depletion of sCLU synergistically increased GCB sensitivity in
      Bel7402 and SMMC7721 cells and induced cell apoptosis. Based on the PCR array
      analysis, sCLU depletion also resulted in the up-regulation of BNIP1, GADD45A,
      TNFRSF10A, and TRADD and down-regulation of AKT1 in Bel7402 and SMMC7721 cells
      compared with the parental controls. These results were further supported by a
      Western blot analysis, which showed increased GADD45a protein expression and the
      decreased expression of phosphorylated AKT. GADD45a overexpression also increased
      the sensitivity to GCB in the Bel7402 and SMMC7721 cells. CONCLUSION: Targeting
      sCLU may be a useful method to enhance the cytotoxic effect of GCB in
      hepatocellular carcinoma.

PMID- 24671453
TI  - Preprocedural rabeprazole treatment before endoscopic submucosal dissection for
      gastric neoplasms.
AB  - BACKGROUND: The maximal effect of proton pump inhibitors (PPI) is reported to
      take 5 days. However, most current protocols start PPI on the day of gastric
      endoscopic submucosal dissection (ESD). AIMS: We aimed to evaluate the benefit of
      5 days pretreatment with oral PPI before ESD to prevent bleeding. METHODS: This
      was a prospective randomized controlled trial. Patients were administered oral
      rabeprazole 20 mg or placebo twice daily for 5 days before ESD. Intravenous
      pantoprazole 40 mg was administered 2 h before ESD and at postprocedure day 1,
      and then oral rabeprazole 20 mg was administered once daily. Follow-up endoscopy
      was performed on days 1 and 30. Forty-eight-hour measurement of intragastric pH
      was performed in 26 patients. The primary endpoint was major bleeding related to
      ESD. RESULTS: One-hundred and twenty patients were enrolled. Of these, 45 in the
      pretreatment and 53 in the placebo group were analyzed. Each group had three
      cases of major bleeding. There were no significant differences in the ulcer
      healing rate. Intragastric pH percentage times greater than 4, 5, and 6 were
      86.61 +/- 19.45 %, 83.30 +/- 22.06 %, and 76.86 +/- 25.35 %, respectively, in the
      pretreatment and 85.54 +/- 19.45 %, 84.08 +/- 27.11 %, and 81.53 +/- 27.81 %,
      respectively, in the placebo group, without significant differences. CONCLUSIONS:
      Preprocedural administration of rabeprazole offers no additional benefit over
      postprocedural administration alone in preventing major bleeding after gastric
      ESD.

PMID- 24671455
TI  - Transition-metal-free, visible-light induced cyclization of arylsulfonyl
      chlorides with 2-isocyanobiphenyls to produce phenanthridines.
AB  - 6-Aryl substituted phenanthridines were synthesized via a visible-light-catalyzed
      cyclization of 2-isocyanobiphenyls with arylsulfonyl chlorides under oxidant-free
      and transition-metal-free conditions. This transformation represents an efficient
      and attractive synthetic utilization of arylsulfonyl chlorides. 

PMID- 24671454
TI  - Monitored anesthesia care without endotracheal intubation is safe and efficacious
      for single-balloon enteroscopy.
AB  - BACKGROUND: General endotracheal (GET) anesthesia is often used during single
      balloon enteroscopy (SBE). However, there is currently limited data regarding
      monitored anesthesia care (MAC) without endotracheal intubation for this
      procedure. AIMS: The aim of the study was to determine the safety and efficacy of
      MAC sedation during SBE and to identify risk factors for adverse events. METHODS:
      All patients who underwent SBE and SBE-assisted endoscopic retrograde
      cholangiopancreatography between June 2011 and July 2013 at a tertiary-care
      referral center were studied in a retrospective analysis of a prospectively
      collected database. Patients received MAC anesthesia or GET. The main outcome
      measurements were sedation-related adverse events, diagnostic yield, and
      therapeutic yield. RESULTS: Of the 178 cases in the study, 166 cases (93 %) were
      performed with MAC and 12 (7 %) with GET. Intra-procedure sedation-related
      adverse events occurred in 17 % of cases. The most frequent event was transient
      hypotension requiring pharmacologic intervention in 11.8 % of procedures. In MAC
      cases, the diagnostic yield was 58.4 % and the therapeutic yield was 30.1 %.
      Anesthesia duration was strongly associated with the occurrence of a sedation
      related adverse event (P = 0.005). CONCLUSIONS: MAC is a safe and efficacious
      sedation approach for most patients undergoing SBE. Sedation-related
      complications in SBE are uncommon, but are more frequent in longer procedures.

PMID- 24671456
TI  - Development of the smartphone-based colorimetry for multi-analyte sensing arrays.
AB  - Here we report development of a smartphone app (application) that digitizes the
      colours of a colorimetric sensor array. A conventional colorimetric sensor array
      consists of multiple paper-based sensors, and reports the detection results in
      terms of colour change. Evaluation of the colour changes is normally done by the
      naked eye, which may cause uncertainties due to personal subjectivity and the
      surrounding conditions. Solutions have been particularly sought in smartphones as
      they are capable of spectrometric functions. Our report specifically focuses on
      development of a practical app for immediate point-of-care (POC) multi-analyte
      sensing without additional devices. First, the individual positions of the
      sensors are automatically identified by the smartphone; second, the colours
      measured at each sensor are digitized based on a correction algorithm; and third,
      the corrected colours are converted to concentration values by pre-loaded
      calibration curves. All through these sequential processes, the sensor array
      taken in a smartphone snapshot undergoes laboratory-level spectrometry. The
      advantages of inexpensive and convenient paper-based colorimetry and the
      ubiquitous smartphone are tied to achieve a ready-to-go POC diagnosis. 

PMID- 24671450
TI  - Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following
      acute coronary syndrome.
AB  - TAK-442 is an oral direct factor Xa inhibitor. We sought to determine the dose
      dependent effect of TAK-442 on major bleeding when added to standard treatment in
      stabilised patients with acute coronary syndrome (ACS). In this phase II double
      blind study, 2,753 ACS patients were randomised to TAK-442 or placebo in addition
      to usual care using a three-stage adaptive design. Patients were randomised to
      placebo in all stages, but doses of TAK-442 escalated from 10 mg BID, 20 mg twice
      daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80
      mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3. Study drug was
      started 36 hours after emergent treatment of ACS and within seven days of
      admission, and continued for 24 weeks. The primary endpoint was incidence of TIMI
      (thrombolysis in myocardial infarction) major bleeding. TIMI major bleeding
      incidence was low, but higher with the pooled TAK-442 doses than with placebo (17
      [0.9%] vs 4 [0.5%]; p=0.47), although the difference was neither significant nor
      dose-dependent. However, a dose response was evident when using the modified ISTH
      scale. The incidence of cardiovascular events was similar among TAK-442 dose
      groups and placebo. When administered over a wide range of doses after an ACS
      event, TAK-442 treatment did not result in a dose-dependent increase in TIMI
      major bleeding, but increased bleeding was observed when a more sensitive
      bleeding scale was used. There was no evidence for efficacy. 

PMID- 24671459
TI  - Patient satisfaction in pediatric surgical care: a systematic review.
AB  - OBJECTIVE: This study seeks to synthesize evidence-based findings related to
      patient satisfaction as a process measure in pediatric surgical care. DATA
      SOURCES: PubMed, CINAHL, Scopus, and the Cochrane Central Register of Controlled
      Trials. REVIEW METHODS: We queried 4 standard search engines (1992-2013) for
      studies specific to pediatric surgical fields in which patient or parent
      satisfaction or experience of care was a primary outcome measure. Data were
      systematically analyzed to determine study characteristics, setting, parent or
      patient focus, measure of experience, and bias. Two independent investigators
      independently reviewed all articles. RESULTS: The initial search yielded 4748
      publications (1503 duplicates), of which 170 underwent full-text review. Thirty
      five were included for analysis; the majority (24/35,77%) were published in the
      last 5 years. Studies examined experience of the child (3/35), parent (23/35), or
      both (9/35). Experience and satisfaction were evaluated either by validated self
      assessment instruments (8), by satisfaction tools (8), or by nonstandard
      institutional or author-developed tools (19). Experience was measured in the
      outpatient (7), preoperative (11), operative (14), and postoperative (3) care
      settings. Specific findings were unique to setting; however, in many studies
      higher satisfaction correlated with education/information giving, health care
      provider interpersonal behaviors, and facile/efficient care processes.
      CONCLUSION: The patient experience of care is a valuable quality measure that is
      being more frequently evaluated as a mechanism to improve pediatric surgical care
      processes. Findings related to patient satisfaction and experience of care may be
      limited due to lack of measurement using validated tools. Findings from this
      review may bear significance as patient experience measures become routinely
      integrated with quality and reimbursement.

PMID- 24671458
TI  - Societal-level Risk Factors Associated with Pediatric Hearing Loss: A Systematic
      Review.
AB  - OBJECTIVE: To determine if the current body of evidence describes specific
      threshold values of concern for modifiable societal-level risk factors for
      pediatric hearing loss, with the overarching goal of providing actionable
      guidance for the prevention and screening of audiological deficits in children.
      DATA SOURCES: Three related systematic reviews were performed. Computerized
      PubMed, Embase, and Cochrane Library searches were performed from inception
      through October 2013 and were supplemented with manual searches. REVIEW METHODS:
      Inclusion/exclusion criteria were designed to determine specific threshold values
      of societal-level risk factors on hearing loss in the pediatric population.
      Searches and data extraction were performed by independent reviewers. RESULTS:
      There were 20 criterion-meeting studies with 29,128 participants. Infants less
      than 2 standard deviations below standardized weight, length, or body mass index
      were at increased risk. Specific nutritional deficiencies related to iodine and
      thiamine may also increase risk, although data are limited and threshold values
      of concern have not been quantified. Blood lead levels above 10 ug/dL were
      significantly associated with pediatric sensorineural loss, and mixed findings
      were noted for other heavy metals. Hearing loss was also more prevalent among
      children of socioeconomically disadvantaged families, as measured by a poverty
      income ratio less than 0.3 to 1, higher deprivation category status, and head of
      household employment as a manual laborer. CONCLUSIONS: Increasing our
      understanding of specific thresholds of risk associated with causative factors
      forms the foundation for preventive and targeted screening programs as well as
      future research endeavors.

PMID- 24671460
TI  - Recurrent Pleomorphic Adenoma of the Parotid Gland: Intraoperative Facial Nerve
      Monitoring during Parotidectomy.
AB  - OBJECTIVE: To determine the benefit to postoperative facial function of
      intraoperative facial nerve monitoring (IFNM) during recurrent pleomorphic
      adenoma (RPA) parotid surgery. STUDY DESIGN: Cohort study with planned data
      collection. SETTING: Chinese PLA General Hospital. SUBJECTS AND METHODS: Fifty
      eight RPA parotidectomies were performed between 2004 and 2012. Recurrence was
      confirmed by histopathologic examination. None of the patients had preoperative
      facial palsy. Electromyography-based IFNM was used in 28 patients; 30 patients
      were unmonitored. The durations of surgery and the severity of postoperative
      facial nerve palsy were compared between the 2 groups. RESULTS: There were no
      significant differences between the 2 groups in the incidence of immediate or
      permanent facial paralysis after RPA parotidectomy (P = .95 and P = .36,
      respectively). However, the differences in the average duration of surgery and
      the severity of postoperative facial nerve palsy after total parotidectomy or
      wide resection were significant (P < .01 and P = .01, respectively). In contrast,
      these differences were not significant after superficial parotidectomies (P = .43
      and P = .49, respectively). The average recovery time of temporary facial nerve
      paralysis was significantly shorter in the monitored group compared with the
      unmonitored group, independent of surgical technique (P < .01). CONCLUSION: The
      use of IFNM during total or wide resection RPA parotidectomy reduced the duration
      of surgery and the incidence of postoperative facial paralysis and enhanced
      recovery. However, there was little impact on facial nerve outcomes when IFNM was
      used during superficial RPA parotidectomy.

PMID- 24671457
TI  - Personally Modifiable Risk Factors Associated with Pediatric Hearing Loss: A
      Systematic Review.
AB  - BACKGROUND: Pediatric hearing loss is an increasingly recognized problem with
      significant implications. Increasing our quantitative understanding of
      potentially modifiable environmental risk factors for hearing loss may form the
      foundation for prevention and screening programs. OBJECTIVE: To determine whether
      specific threshold exposure levels of personally modifiable risk factors for
      hearing loss have been defined, with the overarching goal of providing actionable
      guidance for the prevention of pediatric hearing loss. DATA SOURCES: A systematic
      review was performed. Computerized searches of PubMed, EMBASE, and the Cochrane
      Library were completed and supplemented with manual searches. REVIEW METHODS:
      Inclusion/exclusion criteria were designed to determine specific threshold values
      of personally modifiable risk factors on hearing loss in the pediatric
      population. Searches and data extraction were performed by independent reviewers.
      RESULTS: There were 38 criterion-meeting studies, including a total of 50,651
      subjects. Threshold noise exposures significantly associated with hearing loss in
      youth included: (1) more than 4 hours per week or more than 5 years of personal
      headphone usage, (2) more than 4 visits per month to a discotheque, and (3)
      working on a mechanized farm. Quantified tobacco levels of concern included any
      level of in utero smoke exposure as well as secondhand exposure sufficient to
      elevate serum cotinine. CONCLUSIONS: Specific thresholds analyses are limited.
      Future studies would ideally focus on stratifying risk according to clearly
      defined levels of exposure, in order to provide actionable guidance for children
      and families.

PMID- 24671461
TI  - A Prospective, Randomized Study between the Small Jaw(r) and the Harmonic
      Focus(r) in Open Thyroidectomy.
AB  - OBJECTIVES: LigaSure Small Jaw((r)) (LSJ) was recently developed and applied to
      thyroid surgery along with Harmonic Focus((r)) (HF). We compared the 2 devices in
      open total thyroidectomy for papillary thyroid carcinoma (PTC). STUDY DESIGN: A
      prospective, randomized study. SETTING: Tertiary care center. METHODS: This
      prospective, randomized study included 126 patients enrolled between December
      2011 and June 2012. The numbers of patients in the LSJ group and the HF group
      were 64 and 62, respectively. Operative times, drain output, parathyroid status,
      complications, laboratory data, hospital stay, and analgesia requirements were
      analyzed. RESULTS: Operation time, parathyroid status, postoperative
      complications including hypocalcemia, oral calcium supplement, calcium,
      parathyroid hormone, usage count of painkiller, and hospital stay were not
      different among the 2 groups. Ionized calcium on postoperative days 1, 2, and 10
      was higher in the LSJ group (P = .04, P = .04, P = .01), and drain output was
      lower in the LSJ group (106.8 vs 123.6 mL, P = .01). CONCLUSIONS: Open
      thyroidectomy for PTC using the HF or the LSJ was safe and effective and was not
      associated with any increase in complications. Surgical outcomes and operative
      morbidity were equivalent between the 2 groups.

PMID- 24671462
TI  - Effects of Type 2 Diabetes on Otoacoustic Emissions and the Medial Olivocochlear
      Reflex.
AB  - OBJECTIVE: To demonstrate if cochleopathy in patients with type 2 diabetes with
      normal audiometric hearing threshold can be detected with otoacoustic emissions
      or medial olivocochlear (MOC) reflex measurements. STUDY DESIGN: Cross-sectional
      study. SETTING: Tertiary university teaching hospital. METHODS: The study
      involved 40 type 2 diabetic patients and 24 healthy volunteers. All participants
      who showed normal otoscopic findings, hearing thresholds, and acoustic admittance
      were included. Cochlear activity of participants was evaluated by means of
      distortion product otoacoustic emissions (DPOAEs) and transient otoacoustic
      emissions (TOAEs). The MOC reflex was evoked with contralateral acoustic
      stimulation and recorded with DPOAEs and TOAEs. RESULT: A comparison of DPOAE and
      TOAE levels with a t test between patient and control groups revealed no
      significant difference (P > .05). A comparison of the MOC reflex response between
      the 2 groups also revealed no statistically significant difference (P > .05).
      CONCLUSION: Although decreased OAE amplitude levels were found in diabetic
      patients, there was no statistically significant difference in OAEs and MOC
      reflex. Additional studies are needed to evaluate the role of OAEs and MOC reflex
      in normal-hearing patients with diabetes.

PMID- 24671463
TI  - Pediatric Exercise Stress Laryngoscopy following Laryngotracheoplasty: A
      Comparative Review.
AB  - OBJECTIVE: Exercise-induced airway obstruction in pediatric patients is a unique
      phenomenon with multiple potential etiologies. An accurate diagnosis can be
      challenging to establish in pediatric patients because they are frequently
      asymptomatic at rest. Exercise stress laryngoscopy (ESL) is a modality by which
      pediatric patients can be evaluated under physiologic conditions that produce
      their symptoms. The purpose of this study was to demonstrate (1) the diagnostic
      effectiveness of pediatric ESL and (2) the ability of ESL to guide treatment for
      "normal" and post-airway reconstruction patients with exercise intolerance. STUDY
      DESIGN: Case series with chart review. SETTING: Tertiary care children's
      hospital. SUBJECTS AND METHODS: Patients undergoing ESL for exercise intolerance
      were reviewed. Demographics, surgical history, examination findings, and
      management recommendations were extracted. RESULTS: Thirty-seven patients
      (average age, 13.5 years; range, 5-21 years) were included. There were 14 male
      and 23 female patients. Airway abnormalities became evident in 56% of patients.
      Of these, 24% had focal supraglottic collapse, 43% had evidence of paradoxical
      vocal fold motion, 24% had combined supraglottic and glottic dysfunction, and 9%
      had distal airway abnormalities. Overall, 18 patients had changes in management
      after ESL. Twelve patients in this review had histories of laryngotracheoplasty
      with equivocal findings on operative bronchoscopy. Of these patients, 10 (83%)
      received focal diagnoses after ESL. CONCLUSION: ESL is a contemporary modality by
      which complex patients with undiagnosed exercise intolerance can be effectively
      evaluated. ESL can be an important tool used to guide treatment in pediatric
      patients with exercise-induced dyspnea after airway reconstruction.

PMID- 24671464
TI  - Dual use research: investigation across multiple science disciplines.
AB  - Most recent studies of dual use research have focused on the life sciences,
      although some researchers have suggested that dual use research occurs across
      many disciplines. This research is an initial investigation into the prevalence
      of dual use research in other scientific disciplines by surveying senior editors
      of scientific journals, drawn from Journal Citation Reports. The survey was
      emailed to 7,500 journal editors with a response rate of 10.1 %. Approximately
      4.8 % of life science editors reported they had to consider whether to publish
      dual use research and 38.9 % said they decided to not publish the research in
      question. In disciplines other than the life sciences, 7.2 % of editors from
      other science disciplines reported that they had to consider whether to publish
      dual use research, and 48.4 % declined to publish it. The survey investigated
      relationships between dual use and the journal's source of funding and place of
      publication, but no relationships were found. Further research is needed to
      better understand the occurrence of dual use research in other science
      disciplines. 

PMID- 24671465
TI  - Bone marrow microenvironment confers imatinib resistance to chronic myelogenous
      leukemia and oroxylin A reverses the resistance by suppressing Stat3 pathway.
AB  - Imatinib (IM) is highly effective in treatment of chronic myeloid leukemia (CML)
      but does not eliminate minimal residual disease (MRD), which remains a potential
      source of relapse. IM treatment effectively inhibits BCR-ABL kinase activity in
      CML cells, suggesting that additional kinase-independent mechanisms contribute to
      the presence of MRD. Bone marrow (BM) microenvironment protecting CML cells from
      IM treatment was investigated. Culturing CML cell line K562 in human stromal cell
      line HS-5-derived conditioned medium significantly inhibited apoptosis induced by
      IM, which was soluble factor-mediated drug resistance (SFM-DR). The BM stroma
      derived soluble factors could enhance the resistance of K562 cells to IM by
      increasing Stat3 phosphorylation on tyrosine 705 and subsequently increasing the
      expression of anti-apoptotic proteins and P-glycoprotein (P-gp) in K562 cells.
      Furthermore, the reversal effect of oroxylin A, a naturally monoflavonoid
      isolated from the root of Scutellaria baicalensis Georgi, in K562 cells within
      the SFM-DR model was detected. After treatment of weakly toxic concentration of
      oroxylin A, the apoptosis of K562 cells induced by IM was increased dramatically
      through suppressing Stat3 pathway. In addition, the in vivo study showed that
      oroxylin A potentiates the inhibitory effects of IM on leukemia development by
      suppressing Stat3 pathway in the K562 xenograft model. In conclusion, IM-induced
      resistance in K562 cells within the SFM-DR model correlated with increasing Stat3
      signaling and upregulating P-gp expression through Stat3 pathway. Additionally,
      oroxylin A improved the sensitivity of K562 cells to IM in SFM-DR model and in
      vivo, and the underlying mechanism attributed to the suppression of Stat3
      pathway, which suggested oroxylin A might be a promising agent for treatment
      designed to eradicate MRD in CML patients.

PMID- 24671466
TI  - Fluorescence-based recombination assay for sensitive and specific detection of
      genotoxic carcinogens in human cells.
AB  - In vitro genotoxicity tests are known to suffer from several shortcomings,
      mammalian cell-based assays, in particular, from low specificities. Following a
      novel concept of genotoxicity detection, we developed a fluorescence-based method
      in living human cells. The assay quantifies DNA recombination events triggered by
      DNA double-strand breaks and damage-induced replication fork stalling predicted
      to detect a broad spectrum of genotoxic modes of action. To maximize
      sensitivities, we engineered a DNA substrate encompassing a chemoresponsive
      element from the human genome. Using this substrate, we screened various human
      tumor and non-transformed cell types differing in the DNA damage response, which
      revealed that detection of genotoxic carcinogens was independent of the p53
      status but abrogated by apoptosis. Cell types enabling robust and sensitive
      genotoxicity detection were selected for the generation of reporter clones with
      chromosomally integrated DNA recombination substrate. Reporter cell lines were
      scrutinized with 21 compounds, stratified into five sets according to the
      established categories for identification of carcinogenic compounds: genotoxic
      carcinogens ("true positives"), non-genotoxic carcinogens, compounds without
      genotoxic or carcinogenic effect ("true negatives") and non-carcinogenic
      compounds, which have been reported to induce chromosomal aberrations or
      mutations in mammalian cell-based assays ("false positives"). Our results
      document detection of genotoxic carcinogens in independent cell clones and at
      levels of cellular toxicities <60 % with a sensitivity of >85 %, specificity of
      >=90 % and detection of false-positive compounds <17 %. Importantly, through
      testing cyclophosphamide in combination with primary hepatocyte cultures, we
      additionally provide proof-of-concept for the identification of carcinogens
      requiring metabolic activation using this novel assay system. 

PMID- 24671467
TI  - Does social support predict pregnant mothers' information seeking behaviors on an
      educational website?
AB  - We examine how social support (perceived support and support from a spouse, or
      committed partner) may influence pregnant women's information seeking behaviors
      on a pregnancy website. We assess information seeking behavior among participants
      in a trial testing the effectiveness of a web-based intervention for appropriate
      gestational weight gain. Participants were pregnant women (N = 1,329) recruited
      from clinics and private practices in one county in the Northeast United States.
      We used logistic regression models to estimate the likelihood of viewing
      articles, blogs, frequently asked questions (FAQs), and resources on the website
      as a function of perceived social support, and support from a spouse or
      relationship partner. All models included socio-demographic controls (income,
      education, number of adults and children living at home, home Internet use, and
      race/ethnicity). Compared to single women, women who were married or in a
      committed relationship were more likely to information seek online by viewing
      articles (OR 1.95, 95 % CI [1.26-3.03]), FAQs (OR 1.64 [1.00-2.67]), and blogs
      (OR 1.88 [1.24-2.85]). Women who felt loved and valued (affective support) were
      more likely to seek information by viewing articles on the website (OR 1.19 [1.00
      1.42]). While the Internet provides a space for people who have less social
      support to access health information, findings from this study suggest that for
      pregnant women, women who already had social support were most likely to seek
      information online. This finding has important implications for designing online
      systems and content to encourage pregnant women with fewer support resources to
      engage with content.

PMID- 24671469
TI  - Mechanical, Anatomical, and Kinematic Axis in TKA: Concepts and Practical
      Applications.
AB  - Successful total knee arthroplasty (TKA) has often been based on the restoration
      of the knee to neutral alignment postoperatively. Numerous reports have linked
      malaligned TKA components to increased wear, poor functional outcomes, and
      failure. There have been many different alignment philosophies and surgical
      techniques that have been established to attain the goal of proper alignment,
      which includes such techniques as computerized navigation, and custom cutting
      guides. In addition, these methods could potentially have the added benefit of
      leading to improved functional outcomes following total knee arthroplasty. In
      this report, we have reviewed and analyzed recent reports concerning mechanical,
      anatomic, and kinematic axis/alignment schemes used in total knee arthroplasty. 

PMID- 24671468
TI  - [Neuroendocrine neoplasms of the distal jejunum and ileum].
AB  - Neuroendocrine neoplasms (NEN) of the distal jejunum and ileum derive from
      serotonin-producing enterochromaffin (EC) cells. Due to their low proliferation
      rate and their infiltrative growth, they are often discovered at an advanced
      disease stage when metastasis has already occurred. The biology of these tumours
      is different from other NEN of the digestive tract. In order to standardise and
      improve diagnosis and therapy, the guidelines for the diagnosis and clinical
      management of jejuno-ileal NEN as well as for the management of patients with
      liver and other distant metastases from NEN were revised by the European
      Neuroendocrine Tumour Society (ENETS) in 2012. This review focuses on aspects
      relevant for surgical pathology. 

PMID- 24671470
TI  - Surgical palliation for pancreatic malignancy: practice patterns and predictors
      of morbidity and mortality.
AB  - INTRODUCTION: Most patients with pancreatic cancer present with, or develop,
      biliary or duodenal obstruction. We sought to characterize palliative surgery
      utilization in a contemporary cohort and identify patients at high risk of
      morbidity and mortality. METHODS: The ACS NSQIP database (2005-2011) was queried
      for patients with a pancreatic malignancy undergoing gastrojejunostomy, biliary
      bypass, or laparotomy without resection. Univariate analysis and multivariate
      logistic regression identified factors associated with increased risk of 30-day
      morbidity or mortality. RESULTS: Operations for the 1,126 patients undergoing
      palliative bypass were gastrojejunostomy alone (33%), bile duct bypass alone
      (27%), both (31%), or cholecystojejunostomy (9%). A major complication occurred
      in 20% and mortality in 6.5% at 30 days. Risk factors for morbidity and mortality
      were defined in multivariate models. The number of identified risk factors
      stratified morbidity from 14.8-50% and mortality from 1.6-50% (p < 0.0001 for
      each). Laparotomy alone (n = 622) was associated with lower morbidity than bypass
      (12 vs. 20%, p < 0.0001), but equivalent mortality (5 vs. 6.5%, p = 0.21).
      CONCLUSION: Palliative bypass for pancreatic cancer is associated with a high
      rate of morbidity and mortality. In select patients, this risk may be
      prohibitive. Patient selection reflecting predictors of morbidity and mortality
      may allow for improved outcomes.

PMID- 24671471
TI  - The role of the pathologist in the diagnosis and treatment of dysplasia in
      inflammatory bowel disease.

PMID- 24671472
TI  - The burden of gastrointestinal anastomotic leaks: an evaluation of clinical and
      economic outcomes.
AB  - OBJECTIVE: To evaluate the clinical and economic burden associated with
      anastomotic leaks following colorectal surgery. METHODS: Retrospective data
      (January 2008 to December 2010) were analyzed from patients who had colorectal
      surgery with and without postoperative leaks, using the Premier PerspectiveTM
      database. Data on in-hospital mortality, length of stay (LOS), re-admissions,
      postoperative infection, and costs were analyzed using univariate and
      multivariate analyses, and the propensity score matching (PSM) and generalized
      linear models (GLM). RESULTS: Of the patients, 6,174 (6.18 %) had anastomotic
      leaks within 30 days after colorectal surgery. Patients with leaks had 1.3 times
      higher 30-day re-admission rates and 0.8-1.9 times higher postoperative infection
      rates as compared with patients without leaks (P < 0.001 for both). Anastomotic
      leaks incurred additional LOS and hospital costs of 7.3 days and $24,129,
      respectively, only within the first hospitalization. Per 1,000 patients
      undergoing colorectal surgery, the economic burden associated with anastomotic
      leaks--including hospitalization and re-admission--was established as 9,500 days
      in prolonged LOS and $28.6 million in additional costs. Similar results were
      obtained from both the PSM and GLM for assessing total costs for hospitalization
      and re-admission. CONCLUSIONS: Anastomotic leaks in colorectal surgery increase
      the total clinical and economic burden by a factor of 0.6-1.9 for a 30-day re
      admission, postoperative infection, LOS, and hospital costs.

PMID- 24671473
TI  - Clinical results of selective laser trabeculoplasty in silicone oil-induced
      secondary glaucoma.
AB  - BACKGROUND: To analyze the efficacy of selective laser trabeculoplasty (SLT) on
      silicone oil-induced secondary glaucoma in terms of intraocular pressure (IOP).
      PATIENTS AND METHODS: 42 patients (42 eyes) with silicone oil-induced secondary
      glaucoma were selected, and SLT was performed with 360 degrees  of the trabecular
      meshwork. During the 12-month follow-up, the complications, IOP, and antiglaucoma
      medication usage were observed. RESULTS: The mean IOP decreased from 23.1 +/- 1.9
      mmHg before treatment to 18.4 +/- 3.7 mmHg after treatment (p < 0.05). Mean
      number of antiglaucoma medications used for IOP control also decreased from 2.17
      +/- 1.21 to 1.25 +/- 0.89 (p < 0.05). The 12-month success rate in the total
      sample was 59.5 %. The success rate was 60.7 % (17 eyes) and 57.1 % (eight eyes)
      for phakic and aphakic eyes, respectively (p > 0.05) CONCLUSIONS: SLT is a safe
      and effective option for the treatment of patients with silicone oil-induced
      secondary glaucoma.

PMID- 24671474
TI  - Comment on "Density functional theory analysis of structural and electronic
      properties of orthorhombic perovskite CH3NH3PbI3" by Y. Wang et al., Phys. Chem.
      Chem. Phys., 2014, 16, 1424-1429.
AB  - Yun Wang et al. used density functional theory (DFT) to investigate the
      orthorhombic phase of CH3NH3PbI3, which has recently shown outstanding properties
      for photovoltaic applications. Whereas their analysis of ground state properties
      may represent a valuable contribution to understanding this class of materials,
      effects of spin-orbit coupling (SOC) cannot be overlooked as was shown in earlier
      studies. Moreover, their discussion on optical properties may be misleading for
      non-DFT-experts, and the nice agreement between experimental and calculated band
      gap is fortuitous, stemming from error cancellations between SOC and many-body
      effects. Lastly, Bader charges suggest potential problems during crystal
      structure optimization. 

PMID- 24671475
TI  - Research highlights: printing the future of microfabrication.
AB  - In this issue we highlight emerging microfabrication approaches suitable for
      microfluidic systems with a focus on "additive manufacturing" processes (i.e.
      printing). In parallel with the now-wider availability of low cost consumer-grade
      3D printers (as evidenced by at least three brands of 3D printers for sale in a
      recent visit to an electronics store in Akihabara, Tokyo), commercial-grade 3D
      printers are ramping to higher and higher resolution with new capabilities, such
      as printing of multiple materials of different transparency, and with different
      mechanical and electrical properties. We highlight new work showing that 3D
      printing (stereolithography approaches in particular) has now risen as a viable
      technology to print whole microfluidic devices. Printing on 2D surfaces such as
      paper is an everyday experience, and has been used widely in analytical chemistry
      for printing conductive materials on paper strips for glucose and other
      electrochemical sensors. We highlight recent work using electrodes printed on
      paper for digital microfluidic droplet actuation. Finally, we highlight recent
      work in which printing of membrane-bound droplets that interconnect through
      bilayer membranes may open up an entirely new approach to microfluidic
      manufacturing of soft devices that mimic physiological systems. 

PMID- 24671476
TI  - Case report: traumatic displacement of a cochlear implant magnet.
AB  - OBJECTIVES: To date, over 200 000 cochlear implants (CIs) have been implanted
      worldwide and the incidence is still increasing. We present a case of traumatic
      displacement of CI magnet to raise awareness about this complication and to
      highlight the need for vigilance during surgery as well as for proper counseling.
      METHODS: The clinical presentation of a 1.5-year-old boy with a traumatic
      displacement of a CI magnet was presented and the literature was reviewed for
      this rare complication. RESULTS: After minor head injury, the sound processor
      could no longer connect to the CI. X-ray imaging demonstrated displacement of the
      CI magnet. During revision surgery, the magnet was replaced by a new magnet in
      the silicon holding cap. Intraoperative impedance measurements were normal and
      the CI was successfully activated 4 weeks postoperatively. CONCLUSIONS:
      Clinicians and patients should be aware of the risk of displacement of the CI
      magnet after (minor) head injury. Young boys tend to have a higher risk for this
      complication.

PMID- 24671477
TI  - A fish way out of water: case report of a unique airway foreign body.
AB  - BACKGROUND: Since the time of Chevalier Jackson, innumerable unique foreign
      bodies have been documented and removed. Advances in endoscopic airway management
      have revolutionized the types of foreign bodies that we are able to remove
      without open surgery. The literature on fish aspiration has mostly encompassed
      fish bones and parts, not whole live fish. OBJECTIVE: This study aimed to
      describe the airway management of a high-risk airway foreign body including the
      mobilization and coordination of multiple specialty teams and anesthetic
      management. CASE REPORT: We report a case of a 40-year-old man who aspirated a
      live bluegill fish while attempting to use it as bait. The spike-like nature of
      the bluegill dorsal fin in conjunction with mediastinal air prompted a higher
      level of concern for potential airway compromise and complication with
      extraction. We detail the preparation and management of this patient from
      notification to transportation and ultimately operative intervention. Focus is
      placed on coordination between anesthesia, otolaryngology, and cardiothoracic
      surgery, and the key management decisions. CONCLUSION: High-risk airway foreign
      bodies are always a challenge. When dealing with a live, lodged whole fish, one
      must have creative management ideas. Close coordination and excellent
      communication must occur between teams involved to optimize and maintain control
      of the situation for the best patient outcome.

PMID- 24671478
TI  - Factors associated with recurrence of squamous cell carcinoma involving the
      temporal bone.
AB  - OBJECTIVE: This study aimed to better identify factors associated with recurrence
      of squamous cell carcinoma (SCC) involving the temporal bone. METHODS: A
      retrospective study was conducted at a tertiary hospital. Sixty patients who were
      diagnosed over a 10-year period with SCC involving the temporal bone and
      underwent surgical resection were analyzed. All patients were staged based on the
      University of Pittsburgh staging system. Demographic, intraoperative, and
      pathologic data were analyzed with respect to recurrence. RESULTS: Thirteen
      (21.7%) patients were T1, 8 (13.3%) T2, 7 (11.7%) T3, and 32 (53.3%) T4. Eighteen
      patients (30.0%) recurred in the study period. The mean time to recurrence was
      5.8 months. Tumors originating in the skin overlying the parotid gland and the
      external auditory canal had higher recurrence rates than those from the
      auricle/postauricular skin and temporal bone (P = .05). Direct parotid and
      perineural spread accounted for 15.0% of all routes of temporal invasion but
      resulted in 22.2% of all recurrences (P = .04). Increased N stage was
      statistically associated with increased risk of recurrence (P = .01). Cervical,
      as compared to perifacial and parotid, lymph node involvement was associated with
      increased risk of recurrence (odds ratio = 6.91; 95% confidence interval, 1.11
      42.87). CONCLUSION: We have identified multiple factors that are associated with
      increased recurrence of SCC involving the temporal bone.

PMID- 24671479
TI  - The effects of endoscopic sinus surgery on the postoperative outcomes of open
      rhinoplasty.
AB  - OBJECTIVE: Several studies have advocated concurrent endoscopic sinus surgery and
      rhinoplasty. However, concerns about increased surgical risk, complications, and
      unsuccessful cosmetic outcomes following the concurrent procedures have been
      reported. The aim of this study was to investigate the overall safety of
      concurrent endoscopic sinus surgery and rhinoplasty and to specifically examine
      the effect of endoscopic sinus surgery on cosmetic outcomes. METHODS: We
      retrospectively reviewed 57 patients who underwent concurrent open rhinoplasty
      and endoscopic sinus surgery (ESS). We then selected a control group of patients,
      who underwent rhinoplasty only and were matched with a study group for age, sex,
      external nose deformity, and implant graft material. The postoperative outcomes
      of the 2 groups were compared. RESULTS: Fifty-seven patients underwent concurrent
      open rhinoplasty and ESS. Postoperative assessment showed that a successful
      outcome was achieved in 82.5% of the patients who underwent concurrent procedures
      and in 87.7% of the patients who underwent rhinoplasty only (P = .56). The rate
      of revision due to a dissatisfied outcome was 5 patients (8.7%) in the concurrent
      surgery group and 3 patients (5.3%) in the rhinoplasty-only group (P = .36).
      Minor complications occurred in 6 patients (10.5%) from the group who underwent
      the concurrent procedures and 5 patients (8.8%) from the rhinoplasty-only group
      (P = .76). CONCLUSION: Combined rhinoplasty and endoscopic sinus surgery achieves
      a similar aesthetic outcome to rhinoplasty only, with no significant increase in
      rates of revision or complication.

PMID- 24671480
TI  - Laryngeal granuloma in experimental rats with gastroesophageal reflux disease and
      mechanically injured vocal cord mucosa.
AB  - OBJECTIVE: This study was undertaken to elucidate the mechanisms underlying
      laryngeal granuloma formation in a rat model of gastroesophageal reflux disease
      (GERD) with mechanically injured vocal cord mucosa. METHODS: The rat model of
      GERD was surgically created by tying the pyloric sphincter and ligating the
      transitional region between the forestomach and the glandular portion (limiting
      ridge). The control rats received only a midline incision. In all the animals, a
      plastic bar was inserted into the trachea, and moved vertically thrice in 3
      seconds to cause mechanical injury of the vocal cord mucosa. The rats were
      sacrificed 2 weeks postsurgically, and their pharynx and larynx were observed
      histologically. RESULTS: Granulomas were observed in the vocal cord mucosa of the
      GERD group (3 of 5 animals); they presented a similar pathological structure to
      that of human laryngeal granulomas. In contrast, only abrasions and blisters were
      observed on the vocal cord mucosa in the control group (all 5 animals).
      CONCLUSIONS: The development of laryngeal granuloma may involve both mechanical
      injury and gastric acid reflux.

PMID- 24671482
TI  - Symptom overlap between laryngopharyngeal reflux and glottic insufficiency in
      vocal fold atrophy patients.
AB  - OBJECTIVE: To determine in true vocal fold (TVF) atrophy patients if symptoms of
      throat clearing and mucus sensation, attributed to laryngopharyngeal reflux
      (LPR), are due to glottic insufficiency. Is the TVF atrophy population being
      prescribed proton pump inhibitors unnecessarily? METHODS: A retrospective review
      of patients with TVF atrophy but no other underlying laryngeal pathology seen at
      a tertiary voice center from July 2009 to May 2012 was conducted. Patient
      demographics, symptoms, LPR diagnosis, interventions, and pre-intervention and
      post-intervention Voice Handicap Index-10 (VHI) and Reflux Symptom Index (RSI)
      scores were recorded. RESULTS: Twenty-six patients met inclusion criteria, and
      85% were treated for LPR. Throat clearing and mucus sensation (85%), dysphonia
      (54%), and globus sensation (46%) were recorded. Interventions included LPR
      medical management (65%), vocal fold augmentation (23%), and voice therapy (12%).
      Reflux Symptom Index scores improved in all groups. Voice Handicap Index-10 and
      RSI scores normalized in patients treated with augmentation. Globus was never
      present in patients who received augmentation. CONCLUSION: Throat clearing and
      mucus sensation may be due to underlying glottic insufficiency and changes of the
      aging larynx rather than LPR. High VHI and RSI scores normalized with TVF
      augmentation. Further work is needed to evaluate symptom presentation and risk
      versus benefit of treatment options, especially if it avoids unnecessary proton
      pump inhibitor trials.

PMID- 24671483
TI  - Reliability of clinical office-based laryngeal electromyography in vocally
      healthy adults.
AB  - OBJECTIVE: This study aimed to conduct a 3-session reliability assessment of the
      laryngeal electromyography (LEMG) signal in healthy participants during intensity
      controlled vocalization tasks. We hypothesized that vocal intensity level and
      testing session would affect LEMG measures. METHODS: This prospective study used
      a 2-factor repeated measures design. Seven participants underwent bipolar needle
      LEMG of the right thyroarytenoid muscle. Data were collected over 3 testing
      sessions using vocalization tasks performed with visually guided intensity
      feedback targets (65 and 75 dB SPL). Root mean square amplitudes in microvolts
      were analyzed for within-session and between-session reliability. RESULTS: The
      main effect for intensity was found to approach significance (F = 5.71, P =
      .054). However, intraclass correlation coefficients (ICCs) using a 2-factor mixed
      random effect model indicated poor to fair signal reliability between testing
      sessions (ICC = 0.56 at 65 dB, 0.40 at 70 dB). Intraclass correlation
      coefficients for within-session data indicated excellent reliability for all
      testing conditions (0.84-0.98). CONCLUSION: Using a quantitative analysis
      protocol to inform an essentially qualitative technique, our results indicated
      that there was generally poor to fair reliability in the LEMG signal over testing
      sessions. Vocal intensity was an important variable that affected LEMG signal
      reliability. Standardization of LEMG protocols using vocal control parameters and
      quantitative analyses may help improve LEMG reliability in clinical settings.

PMID- 24671481
TI  - Communicative participation and quality of life in head and neck cancer.
AB  - OBJECTIVE: The purpose of this study was to determine how a new self-report
      outcome measure of communicative participation, the Communicative Participation
      Item Bank (CPIB), related to disease- and discipline-specific quality of life
      (QOL) outcomes in a head and neck cancer (HNC) population. METHODS: One hundred
      ninety-five individuals treated for HNC completed the CPIB, the University of
      Washington Quality of Life questionnaire (UW-QOL), and the Voice Handicap Index
      10 (VHI-10). RESULTS: Results revealed moderate QOL scores across the UW-QOL
      (mean scores: global QOL = 66; physical subscale = 70; social-emotional subscale
      = 73) and VHI-10 (mean = 16). Correlations between the CPIB and the UW-QOL scores
      were statistically significant (P < .001) but relatively weak (r = .37-.38). As
      hypothesized, a stronger correlation was found between the CPIB and the VHI-10 (r
      = -0.79; P < .001). CONCLUSION: Clinicians may consider adopting the CPIB to
      complement existing tools in assessing communication outcomes after HNC.

PMID- 24671484
TI  - Vulnerability to acoustic trauma in the normal hearing ear with contralateral
      hearing loss.
AB  - OBJECTIVES: We undertook an animal study to investigate the functional and
      histological changes that occur in the normal hearing ear of following acoustic
      trauma. METHODS: As an animal model of unilateral hearing loss, the right ears of
      CBA mice were deafened by cochlear destruction at 6 weeks of age (SSD group). The
      control groups included mice that underwent a sham surgery, and mice that were
      exposed to noise binaurally and monaurally (by plugging the right ear
      completely). At 10 weeks of age, all mice were exposed to acoustic trauma (110 dB
      sound pressure level for 1 hour) that induced a transient threshold shift (TTS).
      Changes in the hearing thresholds of the left ear were assessed over the next 4
      weeks by measuring the auditory brainstem responses (ABRs) and distortion product
      otoacoustic emissions (DPOAEs). RESULTS: Following the noise exposure, the SSD
      group showed a permanent threshold shift (PTS) of about 10 dB, whereas the other
      groups showed full recovery from the TTS. The threshold of the DPOAEs of the left
      ears were increased after noise exposure but returned to normal in all groups,
      with no significant differences among the groups. Histological evaluation showed
      no apparent cellular loss or apoptosis in the left ears of all groups, including
      the SSD group. CONCLUSIONS: These results suggest that normal hearing ears are
      more vulnerable to acoustic trauma following contralateral unilateral cochlear
      ablation. This increased vulnerability may be due to damaged neural structures.

PMID- 24671485
TI  - Airway management and endoscopic treatment of subglottic and tracheal stenosis:
      the laryngeal mask airway technique.
AB  - OBJECTIVES: The objective is to present clinical outcomes of subglottic and
      tracheal stenosis treated by flexible bronchoscopic delivery of carbon dioxide
      (CO2) laser via laryngeal mask airway (LMA). METHODS: All consecutive,
      nontracheotomy dependent cases of subglottic and tracheal stenosis treated
      endoscopically over a 4-year period were retrospectively reviewed. The surgical
      approach consisted of radial incisions using a flexible fiber-based CO2 laser,
      balloon dilation, and topical application of mitomycin C. Ventilation during the
      procedure occurred through the LMA, and the CO2 laser fiber was delivered through
      the working channel of a flexible bronchoscope passed through the LMA. Number of
      dilations, period between dilations, and operative times were reviewed. RESULTS:
      Eleven patients who underwent airway intervention during the study period were
      identified. Average follow-up was 28 months. Etiologies of airway stenosis
      included intubation injury (6), idiopathic (4), or autoimmune disease (1),
      requiring an average of 1.3, 1.5, and 3 dilations, respectively. Average
      operative time was 67 minutes. Autoimmune etiology correlated with more frequent
      dilations. CONCLUSION: LMA is an effective way to manage ventilation while
      simultaneously allowing unencumbered flexible bronchoscopic access for laser
      surgery, balloon dilation, and mitomycin C application for airway stenosis. Long
      term success in treating stenosis is achievable using this technique.

PMID- 24671486
TI  - Versatile coordination modes of bis[5-(2-pyridine-2-yl)-1,2,4-triazole-3
      yl]alkanes in Cu(II) complexes.
AB  - Nine new mononuclear and polynuclear Cu(II) complexes [Cu(H2L(2))Cl]Cl.3H2O (1),
      [Cu(H2L(3))Cl]Cl.H2O (2), [Cu(H2L(4))Cl]Cl.2.5H2O (3), [Cu3(MU(3)
      L(1))2(H2O)3](ClO4)2.H2O (4), [Cu4(MU-HL(1))4](ClO4)8.CH3OH.5H2O (5),
      [Cu2(HL(3))2](ClO4)2.2H2O (6a), [Cu2(MU-HL(3))2](ClO4)2.H2O (6b), [Cu2(MU
      HL(3))(L(3))Cu(teta)](ClO4)3.2H2O (7) and [Cu2(H2L(3))2(ox)](ClO4)2.2H2O.2MeOH
      (8) containing [5-(2-pyridine-2-yl)-1,2,4-triazole-3-yl]alkanes (H2L(n), n = 1-4)
      in combination with other ligands, such as chlorido, aqua, triethylenetetramine
      (teta) and/or oxalato (ox(2-)), were synthesized and characterized by various
      techniques such as elemental analysis, FTIR, NMR and UV-Vis spectroscopy. X-ray
      structures of H2L(3) and H2L(4) as well as complexes 1-8 were determined. The X
      ray structures revealed that relatively small composition and structural changes
      in the H2L(n) ligands have a substantial impact on the coordination geometries of
      the complexes themselves as well as on their resulting magnetic properties. It
      has been found that the geometries of the complexes vary from square-pyramidal to
      trigonal-bipyramidal (with tau ranging from 0.00 to 0.96) and, moreover, that the
      trigonal bipyramidal geometry becomes more preferable with the increase in the
      length of the polymethylene chain within the corresponding H2L(n) ligand. The
      magnetic properties of the polynuclear compounds 4, 5, 6, 7 and 8 were analysed
      using the spin Hamiltonian formalism, which revealed the presence of
      antiferromagnetic exchange in the polynuclear systems mediated by the title
      ligands. The significant effect of the geometric parameters on the Cu...Cu
      exchange interactions in the polynuclear complexes is discussed.

PMID- 24671487
TI  - Carpometacarpal dislocation of the thumb associated with fracture of the
      trapezium.
AB  - Carpometacarpal dislocation (CMC) of the thumb associated with fracture of
      trapezium is an extremely rare injury, with only 12 cases that sustained similar
      injuries reported in the literature. In this article, another patient with this
      rare injury was reported, and all previously published cases were extensively
      reviewed. The presented case and all previously published cases had a
      longitudinally oriented trapezium fracture, which is naturally unstable and
      almost always associated with dislocation of the CMC joint. In contrast to
      previous descriptions, we believe that CMC joint dislocation and trapezium
      fracture are not two distinct pathologies that occur simultaneously by chance but
      share cause and consequence. 

PMID- 24671488
TI  - Assessment of functional treatment versus plaster of Paris in the treatment of
      grade 1 and 2 lateral ankle sprains.
AB  - BACKGROUND: Despite the common occurrence of ankle sprains, no treatment is
      considered to be the gold standard for the management of such sprains. We
      assessed functional treatment versus plaster of Paris (POP) for the treatment of
      lateral ankle sprains, with pain and function employed as the outcome measures.
      MATERIALS AND METHODS: 126 Patients were eligible for inclusion. They were
      assigned to either the functional treatment Tubigrip (TG) group or the POP group
      after applying block randomization. Characteristics such as age, dominant ankle,
      and gender were assessed at baseline. Pain and functional assessments were done
      using the visual analog scale (VAS) and the Karlsson score (KS) at baseline (at
      the start of the study) and during the 2nd and 6th weeks, respectively. Data on
      other subjective parameters, such as the number of painkillers used, the number
      of days taken off work, and the number of sleepless nights, were requested from
      the patients at the end of the study. SPSS version 16 was used for analysis, and
      p < 0.05 was taken to indicate significance. RESULTS: 60 Patients completed the
      trial in each group. The mean ages were 28.77 +/- 6.72 in the TG group and 29.83
      +/- 6.30 in the POP group (p = 0.034). There was a slight female predominance.
      Right and left ankles were equally involved in the TG group, while left ankles
      were mainly involved in the POP group. Mean differences in VAS and KS between the
      two groups were statistically significant at the end of the study. The mean
      number of painkillers used by the patients in the TG group was higher than the
      number used in the POP group (p < 0.001). The mean number of days taken off work
      was 4.18 +/- 1.73 days in the TG group, and 6.25 +/- 2.73 days in the POP group
      (p < 0.001). The mean number of sleepless nights was higher in the POP group.
      CONCLUSION: The results of our study indicate that functional treatment provides
      better functional support and pain reduction than a below-knee POP cast. LEVEL OF
      EVIDENCE: Level I.

PMID- 24671489
TI  - Bone graft from greater trochanter in posterior wall fractures with impacted
      fragments.
AB  - BACKGROUND: Posterior wall fracture is the most common acetabular fracture.
      Comminuted fractures with an impacted segment represent a subtype of this injury.
      The subchondral bone of the articular zone is compressed and causes a bone
      defect. The impacted fragment should be isolated, mobilized, and then reduced. A
      bone graft should be used to fill the gap. The other fragments are fixed
      following the reduction of the impacted segment. MATERIALS AND METHODS: Ten
      patients with comminuted fractures and impacted segments with bone defects were
      enrolled in our study, from January 2010 to July 2012. Autogenous bone grafts
      from the greater trochanter were used to fill the gap in all patients. The
      reduction was achieved through the insertion of the graft above the impacted
      fracture, and plate fixation was performed subsequently. Merle d'Aubigne and
      Postel scoring, modified by Matta, was applied to evaluate the patients during
      follow-up. The mean follow-up was 12 months. RESULTS: The clinical results
      included one "excellent", four "very good", four "good" and one "poor". Pain in
      the zone of graft harvesting was not detected in any patient. Femoral head
      necrosis was observed in one case. No other severe complications were detected.
      CONCLUSIONS: Using an autogenous bone graft to fill the bone defect supplies
      excellent mechanical stability without any severe complications at the donor
      site. This surgical technique seems to be effective and safe in treating a
      comminuted fracture of the posterior wall in association with an impacted
      segment. LEVEL OF EVIDENCE: Level IV.

PMID- 24671490
TI  - The siRNA-mediated downregulation of N-Ras sensitizes human melanoma cells to
      apoptosis induced by selective BRAF inhibitors.
AB  - The clinical benefit of selective BRAF inhibitor therapies is limited by the
      emergence of drug resistance. Here, we investigated the molecular basis
      underlying the acquired resistance to a BRAF inhibitor by comparing the signaling
      pathways in the parental A375P cells and the resistant subline (A375P/Mdr). We
      demonstrate that MAPK re-activation does not contribute to the mechanism of
      resistance to UAI-201 of A375P/Mdr cells. The relative quantitative analysis
      using the 2(-DeltaDeltaCt) method revealed that the BRAF inhibitor resistance
      observed in A375P/Mdr cells is not mediated through the overexpression of MDR
      proteins. In particular, we found that the expression of N-Ras was upregulated in
      BRAF inhibitor-resistant A375P/Mdr cells compared with A375P cells. In fact,
      siRNA-mediated N-Ras knockdown partially conferred UAI-201 sensitivity to
      A375P/Mdr cells, implying that N-Ras upregulation confers acquired resistance to
      BRAF inhibition. Notably, the flow cytometric analysis of the N-Ras-knockdown
      A375P/Mdr cells revealed that UAI-201 causes a significant accumulation of cells
      in the G 0/G 1 phase with a concomitant decrease in the number of cells in the S
      and G 2/M phases. However, platelet-derived growth factor receptor beta
      (PDGFRbeta) knockdown failed to sensitize A375P/Mdr cells to growth suppression
      by UAI-201, although a remarkable increase in PDGFRbeta was observed in the A375P
      cells after UAI-201 treatment. Taken together, our results suggest that N-Ras is
      worth targeting to improve the therapeutic outcome of melanomas with acquired
      resistance to BRAF inhibitors. 

PMID- 24671491
TI  - Protection of ginsenoside Rg1 on chondrocyte from IL-1beta-induced mitochondria
      activated apoptosis through PI3K/Akt signaling.
AB  - Chondrocyte apoptosis is closely related to the development and progression of
      osteoarthritis. Ginsenoside Rg1 protects cells by antagonizing apoptosis. This
      study aimed to investigate the protective effect of Rg1 on interleukin 1beta (IL
      1beta)-induced chondrocyte apoptosis and the underlying molecular mechanisms.
      Chondrocytes were harvested from the joints of 1-week-old Sprague-Dawley rats.
      After treated with 10 MUg/mL Rg1 for 2 h, the chondrocytes were cultured with 10
      ng/mL IL-1beta to induce cytotoxicity. Cell viability was assessed with MTT
      assays. Annexin V/propidium iodide staining and terminal deoxynucleotidyl
      transferase dUTP nick-end labeling were used to detect chondrocyte apoptosis. The
      contents of total Akt, phosphorylated Akt (p-Akt), Bcl-2, Bax, and cytochrome C
      (Cyt c) were determined by Western blotting assay. A quantitative colorimetric
      assay was used to determine caspase-3 activity. Our present findings have shown
      that pre-treatment of chondrocytes with Rg1 reduces IL-1beta induced
      cytotoxicity/apoptosis. Rg1 pretreatment also decreases the activity of IL-1beta
      that reduces expression of Bcl-2 and level of p-Akt, and increases Bax activity,
      Cyt c release, and caspase-3 activation. It also reverses the activity of IL
      1beta that reduces the expression of tissue inhibitor of metalloproteinase-1
      expression and increased the synthesis of matrix metalloproteinase-13, with the
      net effect of inhibiting extracellular matrix degradation. These results indicate
      that Rg1 may protect chondrocytes from IL-1beta-induced apoptosis via the
      phosphatidylinositol 3-kinase/protein kinase B signaling pathway, through
      preventing caspase-3 release. 

PMID- 24671492
TI  - miR-217 inhibits invasion of hepatocellular carcinoma cells through direct
      suppression of E2F3.
AB  - The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to the
      development of invasion and metastasis. Recent data strongly suggests the
      important role of miRNAs in cancer progression, including invasion and
      metastasis. Here, we found miR-217 expression was much lower in highly invasive
      MHCC-97H HCC cells and metastatic HCC tissues. Restored miR-217 expression with
      miR-217 mimics inhibited invasion of MHCC-97H cells. Inversely, miR-217
      inhibition enhanced the invasive ability of Huh7 and MHCC-97L cells.
      Mechanically, bioinformatics analysis combined with experimental analysis
      demonstrated E2F3 was a novel direct target of miR-217. Moreover, E2F3 protein
      level was positively associated with HCC metastasis and functional analysis
      confirmed the positive role of E2F3 in HCC cell invasion. Our findings suggest
      miR-217 function as a potential tumor suppressor in HCC progression and miR-217
      E2F3 axis may be a novel candidate for developing rational therapeutic
      strategies. 

PMID- 24671493
TI  - Piperine inhibits type II phosphatidylinositol 4-kinases: a key component in
      phosphoinositides turnover.
AB  - Piperine has been shown to have anti-inflammatory properties. The molecular
      mechanisms by which it mediates anti-inflammatory activities remain elusive. Type
      II phosphatidylinositol 4-kinase(s) are key components in FcepsilonRI receptor
      mediated signaling leading to inflammatory mediators release in RBL-2H3 cells.
      The effects of piperine on IgE-mediated signaling and mast cell degranulation
      were investigated. Pretreatment of RBL-2H3 cells with piperine inhibited IgE
      induced activation of type II PtdIns 4-kinase(s). In vitro lipid kinase assays
      showed piperine-inhibited type II PtdIns 4-kinase activity in a dose-dependent
      fashion with no effect on PtdIns 3-kinase activity. Concomitantly, pretreatment
      of RBL-2H3 cells with piperine also inhibited IgE-induced beta-hexosaminidase
      release in RBL-2H3 cells. These results suggest that type II PtdIns 4-kinases are
      part of piperine-mediated anti-inflammatory signaling mechanisms. 

PMID- 24671494
TI  - Different susceptibility of prefrontal cortex and hippocampus to oxidative stress
      following chronic social isolation stress.
AB  - Chronic oxidative stress plays an important role in depression. The aim of
      present study was to examine the stress-induced changes in serum corticosterone
      (CORT) levels, cytosolic protein carbonyl groups, malondialdehyde (MDA), reduced
      glutathione (GSH), nitric oxide (NO) and total superoxide dismutase (SOD)
      activity in the prefrontal cortex versus hippocampus of male Wistar rats exposed
      to acute (2 h of immobilization or cold), chronic (21d of social isolation)
      stress, and their combination (chronic + acute stress). The subcellular
      distribution of nuclear factor-kappaB (NF-kappaB) and cytosolic cyclooxygenase 2
      (COX-2) protein expressions were also examined. Depressive- and anxiety-like
      behaviors were assessed via the forced swim, sucrose preference, and marble
      burying tests in chronically isolated rats. Although both acute stressors
      resulted in elevated CORT, increased MDA in the prefrontal cortex and NF-kappaB
      activation accompanied by increased NO in the hippocampus were detected only
      following acute cold stress. Chronic isolation resulted in no change in CORT
      levels, but disabled appropriate response to novel acute stress and led to
      depressive- and anxiety-like behaviors. Increased oxidative/nitrosative stress
      markers, likely by NF-kappaB nuclear translocation and concomitant COX-2
      upregulation, associated with decreased SOD activity and GSH levels, suggested
      the existence of oxidative stress in the prefrontal cortex. In contrast,
      hippocampus was less susceptible to oxidative damage showing only increase in
      protein carbonyl groups and depleted GSH. Taken together, the prefrontal cortex
      seems to be more sensitive to oxidative stress than the hippocampus following
      chronic isolation stress, which may be relevant for further research related to
      stress-induced depressive-like behavior.

PMID- 24671495
TI  - Paxillin and focal adhesion kinase colocalise in human skeletal muscle and its
      associated microvasculature.
AB  - Focal adhesion kinase (FAK) and paxillin are functionally linked hormonal- and
      mechano-sensitive proteins. We aimed to describe paxillin's subcellular
      distribution using widefield and confocal immunofluorescence microscopy and test
      the hypothesis that FAK and paxillin colocalise in human skeletal muscle and its
      associated microvasculature. Percutaneous muscle biopsies were collected from the
      m. vastus lateralis of seven healthy males, and 5-MUm cryosections were stained
      with anti-paxillin co-incubated with anti-dystrophin to identify the sarcolemma,
      anti-myosin heavy chain type I for fibre-type differentiation, anti
      dihydropyridine receptor to identify T-tubules, lectin UEA-I to identify the
      endothelium of microvessels and anti-alpha-smooth muscle actin to identify
      vascular smooth muscle cells (VSMC). Colocalisation of anti-paxillin with anti
      dystrophin or anti-FAK was quantified using Pearson's correlation coefficient on
      confocal microscopy images. Paxillin was primarily present in (sub)sarcolemmal
      regions of skeletal muscle fibres where it colocalised with dystrophin (r = 0.414
      +/- 0.026). The (sub)sarcolemmal paxillin immunofluorescence intensity was ~2.4
      fold higher than in sarcoplasmic regions (P < 0.001) with sarcoplasmic paxillin
      immunofluorescence intensity ~10 % higher in type I than in type II fibres (P <
      0.01). In some longitudinally orientated fibres, paxillin formed striations that
      corresponded to the I-band region. Paxillin immunostaining was highest in
      endothelial and VSMC and distributed heterogeneously in both cell types. FAK and
      paxillin colocalised at (sub)sarcolemmal regions and within the microvasculature
      (r = 0.367 +/- 0.036). The first images of paxillin in human skeletal muscle
      suggest paxillin is present in (sub)sarcolemmal and I-band regions of muscle
      fibres and within the microvascular endothelium and VSMC. Colocalisation of FAK
      and paxillin supports their suggested role in hormonal and mechano-sensitive
      signalling.

PMID- 24671496
TI  - High-density single-particle tracking: quantifying molecule organization and
      dynamics at the nanoscale.
AB  - The organization and dynamics of proteins are fundamental parameters for cellular
      function. Their study, at the single-molecule level, provides precise information
      on molecular interactions. Over the last 30 years, the single-particle tracking
      imaging technique has proven its capability to efficiently quantify such
      parameters in many biological systems, with nanometric accuracy and millisecond
      temporal resolutions. Nevertheless, the low concentration of labeling required
      for single-molecule imaging usually prevents the extraction of large statistics.
      The advent of high-density single-molecule-based super-resolution techniques has
      revolutionized the field, allowing monitoring of thousands of biomolecules in the
      minute timescale and providing unprecedented insight into the molecular
      organization and dynamics of cellular compounds. In this issue, I will review the
      main principles of single-particle tracking, a highly interdisciplinary technique
      at the interface between microscopy, image analysis and labeling strategies. I
      will point out the advantages brought by high-density single-particle tracking
      which will be illustrated with a few recent biological results. 

PMID- 24671497
TI  - A fast, low cost, and highly efficient fluorescent DNA labeling method using
      methyl green.
AB  - The increasing need for multiple-labeling of cells and whole organisms for
      fluorescence microscopy has led to the development of hundreds of fluorophores
      that either directly recognize target molecules or organelles, or are attached to
      antibodies or other molecular probes. DNA labeling is essential to study nuclear
      chromosomal structure, as well as for gel staining, but also as a usual
      counterstain in immunofluorescence, FISH or cytometry. However, there are
      currently few reliable red to far-red-emitting DNA stains that can be used. We
      describe herein an extremely simple, inexpensive and robust method for DNA
      labeling of cells and electrophoretic gels using the very well-known histological
      stain methyl green (MG). MG used in very low concentrations at physiological pH
      proved to have relatively narrow excitation and emission spectra, with peaks at
      633 and 677 nm, respectively, and a very high resistance to photobleaching. It
      can be used in combination with other common DNA stains or antibodies without any
      visible interference or bleed-through. In electrophoretic gels, MG also labeled
      DNA in a similar way to ethidium bromide, but, as expected, it did not label RNA.
      Moreover, we show here that MG fluorescence can be used as a stain for direct
      measuring of viability by both microscopy and flow cytometry, with full
      correlation to ethidium bromide staining. MG is thus a very convenient
      alternative to currently used red-emitting DNA stains.

PMID- 24671498
TI  - What's left inside.

PMID- 24671499
TI  - No overall increased risk of cancer in patients with rheumatoid arthritis: a
      nationwide dynamic cohort study in Taiwan.
AB  - The association between rheumatoid arthritis (RA) and cancer is still
      controversial. This study aimed to estimate cancer incidence (both overall and
      site-specific) among patients with RA and to determine whether their cancer risk
      was higher than in the general population. We used the nationwide dynamic cohort
      from the National Health Insurance Research Database of Taiwan and obtained a
      total of 30,504 patients with no history of cancer who were newly diagnosed with
      RA between 1996 and 2008; they were followed up until 2010. Standardized
      incidence ratios (SIR) by age for various types of cancer were calculated in 5
      year calendar periods by 5-year age intervals (quinquinquennium) to compare
      elevated risk of increasing age and increased cancer rate in later calendar years
      in Taiwan. During 225,432 person-years of follow-up, 1,595 cancers occurred,
      corresponding to 7.08 per 1,000 person-years. The SIR for all cancers was 0.93
      (95 % CI 0.88-0.97). Most cancers were found in the first 2 years after diagnosis
      of RA, but the incidence decreased afterward. A significant excess of Hodgkin's
      lymphoma (SIR 3.31, 95 % CI 1.24-8.81) and non-Hodgkin's lymphoma (SIR 3.18, 95 %
      CI 2.64-3.83) was seen among patients with RA, whereas the risk of colorectal
      cancer was 29 % lower than the general population. In conclusion, this study
      showed that patients with RA do not have increased overall risk of cancers but
      have higher risk of hematologic malignancies and lower risk of colorectal cancer,
      than the general population.

PMID- 24671500
TI  - Hyperleptinemia independent of body adiposity in women with fibromyalgia.
AB  - The prevalence of overweight and obesity in patients with fibromyalgia is high,
      which makes these patients more likely to trigger metabolic changes. It is also
      uncertain whether the clinical manifestations of fibromyalgia alter the
      metabolism in these patients. This study investigates the influence of adiposity
      indicators and presence of fibromyalgia on leptin and acylated ghrelin levels,
      which are hormones responsible for controlling energy homeostasis. Seventeen
      women with fibromyalgia (patients) and fifteen healthy women (controls) were
      evaluated. Pain intensity, physical activity level characteristics and leptin and
      acylated ghrelin levels were assessed. General linear models, using a main
      effects model, were used to test the effect of fibromyalgia (patients vs.
      controls) on the relationship of leptin and acylated ghrelin with anthropometric
      indicators [body mass index, waist circumference (WC) and WC by height]. Patients
      showed higher leptin levels (controls: 9.1 +/- 6.7 vs. patients: 22.4 +/- 10.6
      ng/mL; p < 0.01) and lower acylated ghrelin levels (controls: 188.7 +/- 103.4 vs.
      patients: 126.7 +/- 47.8 pg/mL; p = 0.04). The anthropometric variables, entered
      into linear models as independent variables, significantly influenced both leptin
      and acylated ghrelin levels (p < 0.01). The explained variance (R(2)) of the
      models containing leptin was higher (R(2) = 0.52-0.61) compared to the models
      containing acylated ghrelin (R(2) = 0.24-0.27). When analyzing the influence of
      the presence of fibromyalgia (study group: women with fibromyalgia vs. healthy
      women), only the leptin levels were influenced. High leptin levels independent of
      adiposity in women with fibromyalgia may be associated with the clinical
      condition of this syndrome.

PMID- 24671501
TI  - A randomized, double-blind, and placebo-controlled multicenter clinical trial of
      a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese
      active rheumatoid arthritis patients with an inadequate response to methotrexate.
AB  - To assess the clinical efficacy as well as safety profiles of Leining, a novel
      cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment
      of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical
      response to methotrexate (MTX). In this 24-week, randomized, double-blind,
      placebo-controlled multicenter study, a total of 440 Chinese patients with active
      RA with an inadequate response to MTX were randomly assigned to receive Leining
      (10 mg/kg) or placebo. Clinical response was assessed using the American College
      of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as
      the primary major endpoints. Disease activity scores in 28 joints with
      erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate
      disease activity. After 24 weeks of treatment, significantly more patients in
      Leining group achieved ACR20 response than those in placebo group (70.61 vs.
      46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were
      significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001
      and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was
      significantly reduced compared to that in placebo group, with greater clinically
      meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates
      of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were
      greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p
      < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of
      adverse events was similar in both Leining and placebo groups. No neutralizing
      antibodies were detected. Leining demonstrated clinically meaningful efficacy
      compared with placebo in Chinese patients with active RA despite MTX therapy.
      Administration of Leining in combination with MTX for 24 weeks was well
      tolerated.

PMID- 24671502
TI  - Assessment of opioid receptor MU1 gene A118G polymorphism and its association
      with pain intensity in patients with fibromyalgia.
AB  - Fibromyalgia may present with widespread pain and tenderness, fatigue, anxiety,
      and depression and is associated with a low pain threshold. The etiology of
      fibromyalgia is yet to be ascertained, although both genetic and environmental
      factors may play a role in the susceptibility of patients to fibromyalgia.
      Various genetic variations have been investigated to explain fibromyalgia
      susceptibility and differences in pain sensitivity, pain threshold, and
      tolerance. The A118G rs1799971 polymorphism in the opioid receptor MU1 gene
      (OPRM1) is one of the candidate genes. We hypothesized that the OPRM1
      polymorphism may play a role in fibromyalgia susceptibility and impact the pain
      intensity and pain-related symptoms in fibromyalgia patients. This study
      comprised of 108 patients with fibromyalgia and 100 healthy controls. Overall,
      the 118G allele frequency was 16.3 % and was significantly lower in patients with
      fibromyalgia than in the control group (13.9 and 19 %, respectively). No
      difference was observed between fibromyalgia patients with and without the A118G
      allele with regard to the Beck Depression Inventory, widespread pain index,
      symptom severity, and Fibromyalgia Impact Questionnaire scores. All body parts of
      patients with fibromyalgia demonstrated lower pressure pain thresholds (PPT)
      compared to controls. The PPTs were higher in the 118 A/A genotype carrier
      fibromyalgia patients than in 118*/G carriers; however, the differences were not
      significant. As the A118G polymorphism frequency was lower in fibromyalgia
      patients, this polymorphism may exert a protective effect against fibromyalgia in
      Turkish women. However, the OPRM1 polymorphism does not have a significant effect
      on pressure pain and fibromyalgia severity.

PMID- 24671504
TI  - Interview with Tomoki Ogoshi.

PMID- 24671503
TI  - The relationship between mean platelet volume and thrombosis recurrence in
      patients diagnosed with antiphospholipid syndrome.
AB  - Increased mean platelet volume (MPV) is associated with platelet reactivity and
      is a predictor of cardiovascular risk and unprovoked venous thromboembolism. The
      aim of our study was to evaluate MPV in patients with confirmed antiphospholipid
      antibody syndrome (APS) and to identify the correlation between the value of MPV
      and the recurrence of thrombosis. The studied group consists of 247 patients with
      a history of thrombosis and/or pregnancy loss (median age 38, range 18-66 years)
      classified as APS group (n = 70) or APS negative patients (n = 177) according to
      the updated Sapporo criteria. The control group consisted of 98 healthy subjects.
      MPV was significantly higher in the group of patients with clinically and
      laboratory confirmed APS (median 7.85, range 4.73-12.2 fl) in comparison with the
      controls. It was also higher than in APS negative patients (7.61, range 5.21-12.3
      fl). APS patients with triple positivity for antiphospholipid antibodies with
      respect to Miyakis classification categories had higher MPV values than other APS
      patients (9.69 +/- 1.85 vs. 7.29 +/- 1.3 fl, p = 0.001). Recurrent thrombotic
      episodes were observed in 83 patients, but among the triple positive high-risk
      patients with APS in 80 % cases (p = 0.0046). In receiver operating
      characteristic curve analysis, the value of MPV level for thrombosis recurrence
      prediction in the APS group with sensitivity of 86 % and specificity of 82 % was
      7.4 fl. In the multivariate logistic regression model, MPV above 7.4 fl (OR 3.65;
      95 % CI 1.38-9.64, p = 0.009) significantly predicts thrombosis recurrence. Our
      results identify the value of MPV as a prognostic factor of thrombosis recurrence
      in patients with APS.

PMID- 24671506
TI  - Characterisation of the conformational changes in platelet factor 4 induced by
      polyanions: towards in vitro prediction of antigenicity.
AB  - Heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced immune
      reaction affecting blood cells. Its antigen is formed when the chemokine platelet
      factor 4 (PF4) complexes with polyanions. By assessing polyanions of varying
      length and degree of sulfation using immunoassay and circular dichroism (CD)
      spectroscopy, we show that PF4 structural changes resulting in antiparallel beta
      sheet content >30% make PF4/polyanion complexes antigenic. Further, we found that
      polyphosphates (polyP-55) induce antigenic changes on PF4, whereas fondaparinux
      does not. We provide a model suggesting that conformational changes exposing
      antigens on PF4/polyanion complexes occur in the hairpin involving AA 32-38,
      which form together with C-terminal AA (66-70) of the adjacent PF4 monomer a
      continuous patch on the PF4 tetramer surface, explaining why only tetrameric PF4
      molecules express "HIT antigens". The correlation of antibody binding in
      immunoassays with PF4 structural changes provides the intriguing possibility that
      CD-spectroscopy could become the first antibody-independent, in vitro method to
      predict potential immunogenicity of drugs. CD-spectroscopy could identify
      compounds during preclinical drug development that induce PF4 structural changes
      correlated with antigenicity. The clinical relevance can then be specifically
      addressed during clinical trials. Whether these findings can be transferred to
      other endogenous proteins requires further studies. 

PMID- 24671509
TI  - Systematic review and meta-analysis of age at menarche and risk of type 2
      diabetes.
AB  - The relation of early menarche with type 2 diabetes mellitus (T2DM) remains
      inconsistent across studies. The objective of this systematic review and meta
      analysis of published population-based observational studies was to assess the
      association between age at menarche and T2DM risk. We searched online data bases
      through December 2013 and examined the reference lists of pertinent articles.
      Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated
      with a random-effects model. A total of 14 effect estimates from 10 eligible
      studies (three cross-sectional and seven cohort studies) included 315,428
      participants and 22,085 cases of T2DM. Compared with the highest or middle
      category, women in the lowest category of age at menarche had higher risk of T2DM
      [summary RR (95 % CI) 1.22 (1.17, 1.28)]. These results were consistent between
      studies that conducted in the United States and in Europe. The association
      between age at menarche and T2DM was slightly stronger for cohort than for cross
      sectional studies. These findings strongly support an association between younger
      age at menarche and increased risk of T2DM. Age at menarche may help identify
      women with increased risk of developing T2DM. 

PMID- 24671507
TI  - A randomized phase II efficacy and safety study of vandetanib (ZD6474) in
      combination with bicalutamide versus bicalutamide alone in patients with
      chemotherapy naive castration-resistant prostate cancer.
AB  - PURPOSE: To investigate the efficacy and safety of combining vandetanib, an
      orally available multi-targeted tyrosine kinase inhibitor of vascular endothelial
      growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR),
      with bicalutamide in patients with metastatic castration-resistant prostate
      cancer (mCRPC). METHODS: This was an open-label, randomized phase II multi-center
      study. Eligible patients had rising PSA on androgen deprivation therapy, minimal
      symptoms and were chemotherapy-naive. Protocol therapy was either vandetanib 300
      mg oral daily plus bicalutamide 50 mg oral daily (Arm A) or bicalutamide 50 mg
      oral daily alone (Arm B) with cross-over to vandetanib monotherapy at
      progression. The primary endpoint was PSA response (>= 50 % decline from
      baseline). RESULTS: Thirty-nine patients were recruited, 19 in Arm A and 20 in
      Arm B. PSA response was comparable in Arm A and Arm B (18 vs. 19 %). Time to PSA
      progression was 3.16 months (95 % confidence interval (CI): 1.09, not reached
      (NR)) for Arm A and 3.09 months (95 % CI: 1.22, NR) for Arm B. Treatment
      discontinuation due to adverse events was more common in Arm A compared to Arm B
      (42 vs. 5 %; p = 0.019). Treatment with vandetanib was associated with a
      reduction in soluble VEGFR-2 levels after two cycles but an increase in plasma
      VEGF levels. CONCLUSION: The combination of vandetanib and bicalutamide was
      associated with considerable toxicity and did not have superior efficacy over
      bicalutamide alone. Further evaluation of this combination is not warranted in
      mCRPC.

PMID- 24671508
TI  - The interactome of the atypical phosphatase Rtr1 in Saccharomyces cerevisiae.
AB  - The phosphatase Rtr1 has been implicated in dephosphorylation of the RNA
      Polymerase II (RNAPII) C-terminal domain (CTD) during transcription elongation
      and in regulation of nuclear import of RNAPII. Although it has been shown that
      Rtr1 interacts with RNAPII in yeast and humans, the specific mechanisms that
      underlie Rtr1 recruitment to RNAPII have not been elucidated. To address this, we
      have performed an in-depth proteomic analysis of Rtr1 interacting proteins in
      yeast. Our studies revealed that hyperphosphorylated RNAPII is the primary
      interacting partner for Rtr1. To extend these findings, we performed quantitative
      proteomic analyses of Rtr1 interactions in yeast strains deleted for CTK1, the
      gene encoding the catalytic subunit of the CTD kinase I (CTDK-I) complex.
      Interestingly, we found that the interaction between Rtr1 and RNAPII is decreased
      in ctk1Delta strains. We hypothesize that serine-2 CTD phosphorylation is
      required for Rtr1 recruitment to RNAPII during transcription elongation.

PMID- 24671510
TI  - Differences in pancreatic volume, fat content, and fat density measured by
      multidetector-row computed tomography according to the duration of diabetes.
AB  - Pancreatic volume and fat content might be associated with beta-cell function or
      insulin resistance (IR). We investigated the difference in pancreatic volume and
      fat content between age- and body mass index (BMI)-matched normal subjects and
      patients with having different durations of type 2 diabetes (T2D). We compared
      pancreatic volume and fat parameters between 50 age- and BMI-matched normal
      subjects, 51 subjects with newly diagnosed type 2 diabetes (T2D-new), 53 subjects
      with T2D <5 years (T2D<5Y), and 52 subjects with T2D >=5 years (T2D>=5Y). Age and
      BMI were matched to range of +/-2 years and +/-0.5 kg/m(2), respectively.
      Pancreatic volume and fat were measured by multidetector-row computed tomography
      with 64 detector-row scanner. The difference in Hounsfield units between pancreas
      and spleen (HUp-s) was investigated for fat density. Anthropometric and
      biochemical parameters including the homeostasis model assessment of IR (HOMA-IR)
      and the insulinogenic index (IGI) were measured. Compared with normal subjects,
      patients with T2D had significantly smaller pancreatic volume, greater pancreatic
      fat, and lower HUp-s. Among the groups with T2D, pancreatic volume decreased and
      pancreatic fat percentage and HUp-s increased from the T2D-new to the T2D<5Y and
      T2D>5Y groups. Pancreatic volume and fat and HUp-s values were associated with
      HbA1c and triglyceride levels. Pancreatic volume was correlated with IGI while
      pancreatic fat and HUp-s values were correlated with HOMA-IR. The current study
      suggests that pancreatic volume and fat deposition might be associated with the
      development and progression of T2D in Korean subjects. 

PMID- 24671511
TI  - Enolase-like protein present on the outer membrane of Pseudomonas aeruginosa
      binds plasminogen.
AB  - Pseudomonas aeruginosa is one of the pathogenic bacteria which utilize binding of
      the host plasminogen (Plg) to promote their invasion throughout the host tissues.
      In the present study, we confirmed that P. aeruginosa exhibits binding affinity
      for human plasminogen. Furthermore, we showed that the protein detected on the
      cell wall of P. aeruginosa and binding human plasminogen is an enolase-like
      protein. The hypothesis that alpha-enolase, a cytoplasmatic glycolytic enzyme,
      resides also on the cell surface of the bacterium was supported by electron
      microscopy analysis. The plasminogen-binding activity of bacterial cell wall
      outer membrane enolase-like protein was examined by immunoblotting assay. 

PMID- 24671513
TI  - Obituary: John Phillip Nelson MD (1936-2013).

PMID- 24671515
TI  - Finite element based nonlinear normalization of human lumbar intervertebral disc
      stiffness to account for its morphology.
AB  - Disc degeneration, usually associated with low back pain and changes of
      intervertebral stiffness, represents a major health issue. As the intervertebral
      disc (IVD) morphology influences its stiffness, the link between mechanical
      properties and degenerative grade is partially lost without an efficient
      normalization of the stiffness with respect to the morphology. Moreover, although
      the behavior of soft tissues is highly nonlinear, only linear normalization
      protocols have been defined so far for the disc stiffness. Thus, the aim of this
      work is to propose a nonlinear normalization based on finite elements (FE)
      simulations and evaluate its impact on the stiffness of human anatomical
      specimens of lumbar IVD. First, a parameter study involving simulations of
      biomechanical tests (compression, flexion/extension, bilateral torsion and
      bending) on 20 FE models of IVDs with various dimensions was carried out to
      evaluate the effect of the disc's geometry on its compliance and establish
      stiffness/morphology relations necessary to the nonlinear normalization. The
      computed stiffness was then normalized by height (H), cross-sectional area (CSA),
      polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the
      effect of both linear and nonlinear normalizations. In the second part of the
      study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy
      of 14 human lumbar IVDs. Based on the measured morphology and pre-established
      relation with stiffness, linear and nonlinear normalization routines were then
      applied to the compliance of the specimens for each quasi-static biomechanical
      test. The variability of the stiffness prior to and after normalization was
      assessed via coefficient of variation (CV). The FE study confirmed that larger
      and thinner IVDs were stiffer while the normalization strongly attenuated the
      effect of the disc geometry on its stiffness. Yet, notwithstanding the results of
      the FE study, the experimental stiffness showed consistently higher CV after
      normalization. Assuming that geometry and material properties affect the
      mechanical response, they can also compensate for one another. Therefore, the
      larger CV after normalization can be interpreted as a strong variability of the
      material properties, previously hidden by the geometry's own influence. In
      conclusion, a new normalization protocol for the intervertebral disc stiffness in
      compression, flexion, extension, bilateral torsion and bending was proposed, with
      the possible use of MRI and FE to acquire the discs' anatomy and determine the
      nonlinear relations between stiffness and morphology. Such protocol may be useful
      to relate the disc's mechanical properties to its degree of degeneration.

PMID- 24671514
TI  - Does preoperative psychologic distress influence pain, function, and quality of
      life after TKA?
AB  - BACKGROUND: Preoperative psychologic distress is considered to be a risk factor
      for clinical dissatisfaction stemming from persistent pain and physical
      limitations after elective orthopaedic procedures such as lower-extremity
      arthroplasty. However, the degree to which psychologic distress, specifically in
      the form of anxiety and depression, influences surgical results has been poorly
      characterized. QUESTIONS/PURPOSES: We analyzed the effect of preoperative
      psychologic distress on changes in pain, function, and quality of life 1 year
      after elective TKA. METHODS: In this prospective cohort study, we assessed
      patients who underwent TKAs in 2009 and 2010. Before surgery, patients completed
      the Folstein Mini Mental Test, the Hospital Anxiety and Depression Scale (HAD),
      The Knee Society Score((c)), the WOMAC quality-of-life questionnaire, and the VAS
      for pain. The patients were divided into two groups based on the degree of
      psychologic distress on the HAD Scale, and the groups were compared in terms of
      the above-listed clinical outcomes tools 1 year after surgery using multivariate
      linear models. Two hundred sixty-three patients met the inclusion criteria, and
      202 (77%) completed the study protocol. RESULTS: The presence of preoperative
      psychologic distress did not influence 1-year postoperative pain assessment
      (average reduction in pain, 40.33; 95% CI, 36.9-43.8; p = 0.18). The only factor
      influencing change in pain experienced by patients was the preoperative pain
      recorded (R(2) = 0.31; beta = -0.82; p < 0.001). The patients experiencing
      preoperative psychologic distress obtained poorer outcomes in function (R(2) =
      0.16; beta = -5.62; p = 0.001) and quality of life (R(2) = 0.09; beta = -0.46; p
      < 0.001) 1 year after receiving TKA. CONCLUSIONS: The presence of preoperative
      psychologic distress is associated with worse 1-year outcomes for function and
      quality of life in patients undergoing TKA. Interventions designed to reduce
      psychologic distress may be indicated for patients to undergo this type of
      surgery, and incorporation of these data into discussions with patients may
      facilitate informed and shared decision making regarding the surgical treatment
      of knee osteoarthritis. LEVEL OF EVIDENCE: Level II, therapeutic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24671516
TI  - Importance of oxygen spillover for fuel oxidation on Ni/YSZ anodes in solid oxide
      fuel cells.
AB  - Using first principles simulations and the Monte Carlo method, the optimal
      structure of the triple-phase boundaries (TPB) of the Ni/Yttria-Stabilized
      Zirconia (YSZ) anode in solid oxide fuel cells (SOFCs) is determined. Based on
      the new TPB microstructures we reveal different reaction pathways for H2 and CO
      oxidation. In contrast to what was believed in previous theoretical studies, we
      find that the O spillover from YSZ to Ni plays a vital role in electrochemical
      reactions. The H2 oxidation reaction can proceed very rapidly, by means of both
      the H and O spillovers, whereas the CO oxidation can only proceed through the O
      spillover pathway. Further understanding of the roles of defects and dopants
      allows us to explain puzzling experimental observations and to predict ways to
      improve the catalytic performance of SOFCs. 

PMID- 24671518
TI  - Pancreatic resection in elderly patients: should it be denied?
AB  - BACKGROUND: Surgery remains the only potential curative therapy for pancreatic
      cancer, but compromised physiological reserve and comorbidities may deny
      pancreatic resection from elderly patients. METHODS: The medical records of all
      patients who underwent pancreatic resection at our institution (2005-2012) were
      retrospectively reviewed. Postoperative and long-term outcomes were compared
      between patients with cutoff age of 70 years. RESULTS: A total of 228 (66 %) and
      116 (34 %) patients were <70 and >=70 years, respectively. Elderly group had
      worse ASA scores (P < 0.0001) with higher rates of invasive malignant pathologies
      (75 vs. 67 %, P = 0.14), mainly pancreatic ductal adenocarcinoma (58.6 vs. 44.7
      %, P = 0.01). The most common type of resection was pancreaticoduodenectomy (PD)
      (59 %), followed by distal pancreatectomy (19.8 %). Mean hospital stay was
      comparable. Elderly patients had less grade >=IIIb postoperative complications
      (12 vs. 20.1 %; P = 0.04) and higher postoperative mortality rates (12.9 vs. 3.9
      %; P = 0.04). In multivariable Cox proportional hazards model for postoperative
      mortality, age >= 70 years (HR, 3.5; 95 % CI, 1.3-9.3), pancreaticoduodenectomy
      (HR, 12.6; 95 % CI, 1.6-96), and intraoperative blood loss were significant (P =
      0.012; P = 0.015, and P = 0.005, respectively). The overall 5-year survival rates
      for all patients, for patients aged <70 and >=70 years were 56, 55, and 41 %,
      respectively (P = 0.003). CONCLUSIONS: Elderly patients are at higher risk of
      mortality after pancreatic resection than usually reported case series.
      Nonetheless, elderly patients can undergo pancreatic resection with acceptable 5
      year survival results. Our results contribute for a better, informed decision
      making for elderly patients and their family.

PMID- 24671517
TI  - Low anandamide doses facilitate male rat sexual behaviour through the activation
      of CB1 receptors.
AB  - RATIONALE: Endocannabinoids (eCN) exert biphasic effects on several behaviours;
      however, they have only been reported to inhibit male sexual behaviour. eCN, the
      endogenous ligands for CB1 receptors, are released in response to neuronal
      stimulation and regulate the functioning of the mesocorticolimbic system (MCL),
      which is activated by male sexual behaviour. We hypothesised that eCN might exert
      biphasic effects on male rat copulatory behaviour and be released during
      copulation to satiation as a result of the repeated activation of the MCL system.
      OBJECTIVES: The study was conducted to determine if the eCN anandamide exerts
      biphasic effects on sexual behaviour expression of sexually experienced and
      sexually satiated male rats and to establish the possible participation of eCN in
      the sexual satiation phenomenon. METHODS: The eCN anandamide and the CB1 receptor
      antagonist AM251 were systemically administered to sexually experienced or
      sexually satiated rats and their effects on copulatory behaviour analysed.
      RESULTS: Low anandamide doses facilitated sexual behaviour expression in sexually
      experienced and in sexually satiated rats by acting at CB1 receptors. AM251
      blocked the establishment of the sexual inhibition that characterises sexual
      satiation, but did not reverse it once established. CONCLUSIONS: Anandamide
      exerts dose-based biphasic effects on copulatory behaviour of sexually
      experienced male rats and facilitates sexual behaviour expression of sexually
      satiated animals at low doses. eCN participate in the establishment, but not in
      the maintenance of the sexual inhibitory state that characterises the sexual
      satiation phenomenon.

PMID- 24671519
TI  - Elasticity and geometry: a computational model of the Heineke-Mikulicz
      strictureplasty.
AB  - Crohn's disease is a challenging inflammatory process with a propensity for focal
      gastro-intestinal tract inflammation and stricture. Surgically, Crohn's is often
      treated with resection. However, a subtype of diffuse disease with multiple
      strictures is treated by strictureplasty procedures in hope of avoiding short-gut
      syndrome. Prior work by Pocivavsek et al. defined the geometry of a Heineke
      Mikulicz strictureplasty. Here, we bring this analysis one step closer to
      clinical and biological relevance by calculating the mechanical stresses and
      strains that the strictureplasty deformation generates on a model intestinal
      wall. The small bowel is simulated as a linearly elastic isotropic deformable
      cylindrical shell using finite element modeling. Data show a divergence in
      elastic response between the anti-mesenteric and mesenteric halves. The anti
      mesenteric surface shows a bending dominated elastic response that correlates
      with the prior purely geometric analysis. However, the mesenteric half is not a
      neutral bystander during strictureplasty formation, as geometric arguments
      predict. Strong in-plane stretching strains develop in a rim around the image of
      the transverse closure, which may impact local perfusion and serve as sites of
      disease recurrence. Lastly, nearly all the deformation energy is stored in the
      central vertex stitch, placing this part at highest risk of dehiscence. This
      study enhances our understanding of mechanical response in complex nonlinear
      cylindrical geometries like the surgically manipulated intestinal tract. The
      developed framework serves as a platform for future addition of more complex
      clinically relevant parameters to our model, including real tissue properties,
      anisotropy, blood supply modeling, and patient deriver anatomic factors. 

PMID- 24671520
TI  - Remineralization of mechanical loaded resin-dentin interface: a transitional and
      synchronized multistep process.
AB  - This study evaluated the ability of different in vitro mechanical loading tests
      to promote new mineral formation at bonded dentin interfaces. This research
      demonstrated a sequential transition in the dentin remineralizing procedure
      through the analysis of the mineral and matrix gradients. Mechanical loading in
      phosphoric acid (PA)-treated samples promoted a generalized increases in relative
      presence of minerals, crystallinity, ratio of phosphate peaks and a decrease in
      the gradient of mineral content. The organic component showed, in general terms,
      an increase in crosslinking. [Formula: see text]-helices incremented in sine and
      square waveform loading. In EDTA + SB specimens, the relative mineral
      concentration incremented when loading in hold, in general. Nonuniform parameters
      of Bis-GMA and adhesive penetration were encountered in both groups. PA + SB
      promoted the highest dentin mineralization degree when loading in square, based
      on the increase in the relative presence of minerals and crystallinity. EDTA + SB
      produced any advance crystallographic maturity at the interface. High
      crosslinking parameters and conformational changes in proteins in PA-treated
      specimens indicated, indirectly, that the first remineralization is
      intrafibrillar. 

PMID- 24671522
TI  - In vivo prostacyclin biosynthesis and effects of different aspirin regimens in
      patients with essential thrombocythaemia.
AB  - Essential thrombocythaemia (ET) is characterised by enhanced platelet generation
      and thrombosis. Once daily (od) aspirin incompletely inhibits platelet
      thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to
      fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin
      (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET
      patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary
      metabolite, 2,3-dinor-6-keto-PGF1alpha (PGI-M). Moreover, in a crossover study 22
      patients poorly responsive to standard aspirin based on serum TXB2 levels (>=4
      ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg
      od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours
      after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy
      subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo
      TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as
      compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients
      appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin
      regimen, demonstrating its vascular safety for future trials. 

PMID- 24671521
TI  - Toward the computer-aided discovery of FabH inhibitors. Do predictive QSAR models
      ensure high quality virtual screening performance?
AB  - Antibiotic resistance has increased over the past two decades. New approaches for
      the discovery of novel antibacterials are required and innovative strategies will
      be necessary to identify novel and effective candidates. Related to this problem,
      the exploration of bacterial targets that remain unexploited by the current
      antibiotics in clinical use is required. One of such targets is the beta-ketoacyl
      acyl carrier protein synthase III (FabH). Here, we report a ligand-based modeling
      methodology for the virtual-screening of large collections of chemical compounds
      in the search of potential FabH inhibitors. QSAR models are developed for a
      diverse dataset of 296 FabH inhibitors using an in-house modeling framework. All
      models showed high fitting, robustness, and generalization capabilities. We
      further investigated the performance of the developed models in a virtual
      screening scenario. To carry out this investigation, we implemented a
      desirability-based algorithm for decoys selection that was shown effective in the
      selection of high quality decoys sets. Once the QSAR models were validated in the
      context of a virtual screening experiment their limitations arise. For this
      reason, we explored the potential of ensemble modeling to overcome the
      limitations associated to the use of single classifiers. Through a detailed
      evaluation of the virtual screening performance of ensemble models it was
      evidenced, for the first time to our knowledge, the benefits of this approach in
      a virtual screening scenario. From all the obtained results, we could arrive to a
      significant main conclusion: at least for FabH inhibitors, virtual screening
      performance is not guaranteed by predictive QSAR models.

PMID- 24671523
TI  - Concentration dependence of optical clearing on the enhancement of laser-scanning
      optical-resolution photoacoustic microscopy imaging.
AB  - Quantitative analysis of optical clearing effects (OCE) induced by hyperosmotic
      agents is very important to optical tissue clearing applications in biomedical
      diagnostic imaging and therapeutics. This study aims at investigating the effect
      of glycerol concentration on the laser-scanning optical-resolution photoacoustic
      microscopy (LSOR-PAM) imaging contrast and light penetration depth. The
      photoacoustic (PA) signal amplitude changes are evaluated as a function of the
      concentration of glycerol. The results reveal that the PA signal amplitudes are
      enhanced with the glycerol concentration increasing, and also show that higher
      concentration of glycerol produces better light penetration and OCE on a phantom.
      The PA signal amplitude increases only 8.1% for 20% glycerol, but for higher
      concentrations, the increases are 76% and 165% for 40% and 60% glycerol,
      respectively. This preliminary study demonstrates that application of glycerol as
      an optical contrast agent reduces the tissue scattering and is beneficial to PAM
      imaging and optical diagnosis in clinical dermatology.

PMID- 24671525
TI  - Basic physiochemical and rheological properties of detergent sclerosants.
AB  - OBJECTIVES: To determine the basic physiochemical properties and rheological
      activity of detergent sclerosants. METHODS: Sodium tetradecyl sulphate and
      polidocanol liquid and foam sclerosants were investigated in a range of
      concentrations (0.1-3%), liquid-plus-air fractions (1+2 to 1+8) and dilutions in
      water (stock solutions) or in normal saline. The embolic agent ethanol was
      investigated for comparison. Density was measured using a digital balance.
      Surface tension was measured by the Du Nuoy ring method and used to determine the
      critical micellar concentration. Viscosity was measured using a cone-plate
      rheometer for liquid and a modified parallel plate method for foam. RESULTS:
      Liquid sclerosant density decreased as the sclerosant concentration increased
      while foam density decreased with the increasing air fraction. The critical
      micellar concentration of polidocanol was 0.002% in both normal saline and water
      while that of sodium tetradecyl sulphate was 0.075% in normal saline and 0.200%
      in water. Viscosity of liquid sodium tetradecyl sulphate was lower than that of
      polidocanol. Foam sclerosants were at least 10,000-fold more viscous than liquid
      sclerosants and ethanol. All agents demonstrated a Non-Newtonian shear-thinning
      behaviour with a fall in viscosity at lower shear rates (<10 s(-1)). Polidocanol
      (but not sodium tetradecyl sulphate) foam viscosity progressively increased with
      increasing sclerosant concentration and liquid-plus-air fractions. CONCLUSIONS:
      Liquid and foam sclerosants and ethanol are Non-Newtonian shear thinning fluids.
      Foam sclerosants are significantly more viscous than liquid agents.

PMID- 24671524
TI  - Hemoglobin parameters from diffuse reflectance data.
AB  - Tissue vasculature is altered when cancer develops. Consequently, noninvasive
      methods of monitoring blood vessel size, density, and oxygenation would be
      valuable. Simple spectroscopy employing fiber optic probes to measure
      backscattering can potentially determine hemoglobin parameters. However,
      heterogeneity of blood distribution, the dependence of the tissue-volume-sampled
      on scattering and absorption, and the potential compression of tissue all hinder
      the accurate determination of hemoglobin parameters. We address each of these
      issues. A simple derivation of a correction factor for the absorption
      coefficient, MUa, is presented. This correction factor depends not only on the
      vessel size, as others have shown, but also on the density of blood vessels.
      Monte Carlo simulations were used to determine the dependence of an effective
      pathlength of light through tissue which is parameterized as a ninth-order
      polynomial function of MUa. The hemoglobin bands of backscattering spectra of
      cervical tissue are fit using these expressions to obtain effective blood vessel
      size and density, tissue hemoglobin concentration, and oxygenation. Hemoglobin
      concentration and vessel density were found to depend on the pressure applied
      during in vivo acquisition of the spectra. It is also shown that determined
      vessel size depends on the blood hemoglobin concentration used.

PMID- 24671526
TI  - Prevention of pulmonary embolisms associated with vena cava filter implantation.
AB  - OBJECTIVE: To investigate the prevention of pulmonary embolism (PE) by the
      implantation of inferior vena cava filters (IVCFs). METHODS: Data of 1058
      patients treated for lower extremity deep vein thrombosis (DVT) between January
      2005 and January 2012 were analyzed retrospectively and divided into those with
      and without PE. RESULTS: Of the 1058 patients, 34 had PEs (3.2%) and 1024 did
      not. Multivariable analyses showed that PEs were less likely to occur in patients
      with IVCFs than in those without IVCFs (odd ratio [OR] =  0.028, P < 0.001), and
      were more likely to occur in patients with vena cava thrombosis than in those
      without vena cava thrombosis (OR =  19.094, P < 0.001). Analyses stratified by
      DVT site showed that vena cava thrombosis was the only risk factor of PE for
      patients with a left DVT (crude OR =  12.814, P < 0.001), and IVCF implantation
      was the only protective factor for PE for patients with a right or bilateral DVT
      (crude OR =  0.028, P =  0.001). IVCF patency rate for follow-up was 98.7% with
      no filter migration, declination, or failure of expansion. CONCLUSIONS: IVCFs can
      reduce the occurrence of PEs in patients with DVTs.

PMID- 24671527
TI  - Vestibular nucleus neurons respond to hindlimb movement in the decerebrate cat.
AB  - The vestibular nuclei integrate information from vestibular and proprioceptive
      afferents, which presumably facilitates the maintenance of stable balance and
      posture. However, little is currently known about the processing of sensory
      signals from the limbs by vestibular nucleus neurons. This study tested the
      hypothesis that limb movement is encoded by vestibular nucleus neurons and
      described the changes in activity of these neurons elicited by limb extension and
      flexion. In decerebrate cats, we recorded the activity of 70 vestibular nucleus
      neurons whose activity was modulated by limb movements. Most of these neurons
      (57/70, 81.4%) encoded information about the direction of hindlimb movement,
      while the remaining neurons (13/70, 18.6%) encoded the presence of hindlimb
      movement without signaling the direction of movement. The activity of many
      vestibular nucleus neurons that responded to limb movement was also modulated by
      rotating the animal's body in vertical planes, suggesting that the neurons
      integrated hindlimb and labyrinthine inputs. Neurons whose firing rate increased
      during ipsilateral ear-down roll rotations tended to be excited by hindlimb
      flexion, whereas neurons whose firing rate increased during contralateral ear
      down tilts were excited by hindlimb extension. These observations suggest that
      there is a purposeful mapping of hindlimb inputs onto vestibular nucleus neurons,
      such that integration of hindlimb and labyrinthine inputs to the neurons is
      functionally relevant. 

PMID- 24671528
TI  - Self-motion improves head direction cell tuning.
AB  - Head direction (HD) cells respond when an animal faces a particular direction in
      the environment and form the basis for the animal's perceived directional
      heading. When an animal moves through its environment, accurate updating of the
      HD signal is required to reflect the current heading, but the cells still
      maintain a representation of HD even when the animal is motionless. This finding
      suggests that the HD system holds its current state in the absence of input, a
      view that we tested by rotating a head-restrained rat in the presence of a
      prominent visual landmark and then stopping it suddenly when facing the cell's
      preferred firing direction (PFD). Firing rates were unchanged for the first 100
      ms, but then progressively decreased over the next 4 s and stabilized at ~42% of
      their initial values. When the rat was stopped facing away from the PFD, there
      was no initial effect of braking, but the firing rate then increased steadily
      over 4 s and plateaued at ~14% of its peak firing rate, substantially above
      initial background firing rates. In experiment 2, the rat was serially placed
      facing one of eight equidistant directions over 360 degrees  and held there for
      30 s. Compared with the cell's peak firing rate during a passive rotation
      session, firing rates were reduced (51%) for in-PFD directions and increased
      (~300%) from background levels for off-PFD directions, values comparable to those
      observed in the braking protocol. These differential HD cell responses
      demonstrate the importance of self-motion to the HD signal integrity. 

PMID- 24671530
TI  - Unilateral electrical stimulation of rat locus coeruleus elicits bilateral
      response of norepinephrine neurons and sustained activation of medial prefrontal
      cortex.
AB  - The brain stem nucleus locus coeruleus (LC) is thought to modulate cortical
      excitability by norepinephrine (NE) release in LC forebrain targets. The effects
      of LC burst discharge, typically evoked by a strong excitatory input, on cortical
      ongoing activity are poorly understood. To address this question, we combined
      direct electrical stimulation of LC (LC-DES) with extracellular recording in LC
      and medial prefrontal cortex (mPFC), an important cortical target of LC. LC-DES
      consisting of single pulses (0.1-0.5 ms, 0.01-0.05 mA) or pulse trains (20-50 Hz,
      50-200 ms) evoked short-latency excitatory and inhibitory LC responses
      bilaterally as well as a delayed rebound excitation occurring ~100 ms after
      stimulation offset. The pulse trains, but not single pulses, reliably elicited
      mPFC activity change, which was proportional to the stimulation strength. The
      firing rate of ~50% of mPFC units was significantly modulated by the strongest LC
      DES. Responses of mPFC putative pyramidal neurons included fast (~100 ms),
      transient (~100-200 ms) inhibition (10% of units) or excitation (13%) and delayed
      (~500 ms), sustained (~1 s) excitation (26%). The sustained spiking resembled NE
      dependent mPFC activity during the delay period of working memory tasks.
      Concurrently, the low-frequency (0.1-8 Hz) power of the local field potential
      (LFP) decreased and high-frequency (>20 Hz) power increased. Overall, the DES
      induced LC firing pattern resembled the naturalistic biphasic response of LC-NE
      neurons to alerting stimuli and was associated with a shift in cortical state
      that may optimize processing of behaviorally relevant events. 

PMID- 24671529
TI  - Synaptic excitation is regulated by the postsynaptic dSK channel at the
      Drosophila larval NMJ.
AB  - In the mammalian central nervous system, the postsynaptic small-conductance
      Ca(2+)-dependent K(+) (SK) channel has been shown to reduce postsynaptic
      depolarization and limit Ca(2+) influx through N-methyl-d-aspartate receptors. To
      examine further the role of the postsynaptic SK channel in synaptic transmission,
      we studied its action at the Drosophila larval neuromuscular junction (NMJ).
      Repetitive synaptic stimulation produced an increase in postsynaptic membrane
      conductance leading to depression of excitatory postsynaptic potential amplitude
      and hyperpolarization of the resting membrane potential (RMP). This reduction in
      synaptic excitation was due to the postsynaptic Drosophila SK (dSK) channel;
      synaptic depression, increased membrane conductance and RMP hyperpolarization
      were reduced in dSK mutants or after expressing a Ca(2+) buffer in the muscle.
      Ca(2+) entering at the postsynaptic membrane was sufficient to activate dSK
      channels based upon studies in which the muscle membrane was voltage clamped to
      prevent opening voltage-dependent Ca(2+) channels. Increasing external Ca(2+)
      produced an increase in resting membrane conductance and RMP that was not seen in
      dSK mutants or after adding the glutamate-receptor blocker philanthotoxin. Thus
      it appeared that dSK channels were also activated by spontaneous transmitter
      release and played a role in setting membrane conductance and RMP. In mammals,
      dephosphorylation by protein phosphatase 2A (PP2A) increased the Ca(2+)
      sensitivity of the SK channel; PP2A appeared to increase the sensitivity of the
      dSK channel since PP2A inhibitors reduced activation of the dSK channel by evoked
      synaptic activity or increased external Ca(2+). It is proposed that spontaneous
      and evoked transmitter release activate the postsynaptic dSK channel to limit
      synaptic excitation and stabilize synapses. 

PMID- 24671531
TI  - Early vestibular processing does not discriminate active from passive self-motion
      if there is a discrepancy between predicted and actual proprioceptive feedback.
AB  - Most of our sensory experiences are gained by active exploration of the world.
      While the ability to distinguish sensory inputs resulting of our own actions
      (termed reafference) from those produced externally (termed exafference) is well
      established, the neural mechanisms underlying this distinction are not fully
      understood. We have previously proposed that vestibular signals arising from self
      generated movements are inhibited by a mechanism that compares the internal
      prediction of the proprioceptive consequences of self-motion to the actual
      feedback. Here we directly tested this proposal by recording from single neurons
      in monkey during vestibular stimulation that was externally produced and/or self
      generated. We show for the first time that vestibular reafference is equivalently
      canceled for self-generated sensory stimulation produced by activation of the
      neck musculature (head-on-body motion), or axial musculature (combined head and
      body motion), when there is no discrepancy between the predicted and actual
      proprioceptive consequences of self-motion. However, if a discrepancy does exist,
      central vestibular neurons no longer preferentially encode vestibular
      exafference. Specifically, when simultaneous active and passive motion resulted
      in activation of the same muscle proprioceptors, neurons robustly encoded the
      total vestibular input (i.e., responses to vestibular reafference and exafference
      were equally strong), rather than exafference alone. Taken together, our results
      show that the cancellation of vestibular reafference in early vestibular
      processing requires an explicit match between expected and actual proprioceptive
      feedback. We propose that this vital neuronal computation, necessary for both
      accurate sensory perception and motor control, has important implications for a
      variety of sensory systems that suppress self-generated signals. 

PMID- 24671532
TI  - Depressed GABA and glutamate synaptic signaling by 5-HT1A receptors in the
      nucleus tractus solitarii and their role in cardiorespiratory function.
AB  - Serotonin (5-HT), and its 5-HT1A receptor (5-HT1AR) subtype, is a powerful
      modulator of the cardiorespiratory system and its sensory reflexes. The nucleus
      tractus solitarii (nTS) serves as the first central station for visceral afferent
      integration and is critical for cardiorespiratory reflex responses. However, the
      physiological and synaptic role of 5-HT1ARs in the nTS is relatively unknown. In
      the present study, we examined the distribution and modulation of 5-HT1ARs on
      cardiorespiratory and synaptic parameters in the nTS. 5-HT1ARs were widely
      distributed to cell bodies within the nTS but not synaptic terminals. In
      anesthetized rats, activation of 5-HT1ARs by microinjection of the 5-HT1AR
      agonist 8-OH-DPAT into the caudal nTS decreased minute phrenic neural activity
      via a reduction in phrenic amplitude. In brain stem slices, 8-OH-DPAT decreased
      the amplitude of glutamatergic tractus solitarii-evoked excitatory postsynaptic
      currents, and reduced overall spontaneous excitatory nTS network activity. These
      effects persisted in the presence of GABAA receptor blockade and were antagonized
      by coapplication of 5-HT1AR blocker WAY-100135. 5-HT1AR blockade alone had no
      effect on tractus solitarii-evoked excitatory postsynaptic currents, but
      increased excitatory network activity. On the other hand, GABAergic nTS-evoked
      inhibitory postsynaptic currents did not change by activation of the 5-HT1ARs,
      but spontaneous inhibitory nTS network activity decreased. Blocking 5-HT1ARs
      tended to increase nTS-evoked inhibitory postsynaptic currents and inhibitory
      network activity. Taken together, 5-HT1ARs in the caudal nTS decrease breathing,
      likely via attenuation of afferent transmission, as well as overall nTS network
      activity. 

PMID- 24671534
TI  - Finger-thumb coupling contributes to exaggerated thumb flexion in stroke
      survivors.
AB  - The purpose of this study was to investigate altered finger-thumb coupling in
      individuals with chronic hemiparesis poststroke. First, an external device
      stretched finger flexor muscles by passively rotating the metacarpophalangeal
      (MCP) joints. Subjects then performed isometric finger or thumb force generation.
      Forces/torques and electromyographic signals were recorded for both the thumb and
      finger muscles. Stroke survivors with moderate (n = 9) and severe (n = 9) chronic
      hand impairment participated, along with neurologically intact individuals (n =
      9). Stroke survivors exhibited strong interactions between finger and thumb
      flexors. The stretch reflex evoked by stretch of the finger flexors of stroke
      survivors led to heteronymous reflex activity in the thumb, while attempts to
      produce isolated voluntary finger MCP flexion torque/thumb flexion force led to
      increased and undesired thumb force/finger MCP torque production poststroke with
      a striking asymmetry between voluntary flexion and extension. Coherence between
      the long finger and thumb flexors estimated using intermuscular electromyographic
      correlations, however, was small. Coactivation of thumb and finger flexor muscles
      was common in stroke survivors, whether activation was evoked by passive stretch
      or voluntary activation. The coupling appears to arise from subcortical or spinal
      sources. Flexor coupling between the thumb and fingers seems to contribute to
      undesired thumb flexor activity after stroke and may impact rehabilitation
      outcomes. 

PMID- 24671533
TI  - Sensory convergence in the parieto-insular vestibular cortex.
AB  - Vestibular signals are pervasive throughout the central nervous system, including
      the cortex, where they likely play different roles than they do in the better
      studied brainstem. Little is known about the parieto-insular vestibular cortex
      (PIVC), an area of the cortex with prominent vestibular inputs. Neural activity
      was recorded in the PIVC of rhesus macaques during combinations of head, body,
      and visual target rotations. Activity of many PIVC neurons was correlated with
      the motion of the head in space (vestibular), the twist of the neck
      (proprioceptive), and the motion of a visual target, but was not associated with
      eye movement. PIVC neurons responded most commonly to more than one stimulus, and
      responses to combined movements could often be approximated by a combination of
      the individual sensitivities to head, neck, and target motion. The pattern of
      visual, vestibular, and somatic sensitivities on PIVC neurons displayed a
      continuous range, with some cells strongly responding to one or two of the
      stimulus modalities while other cells responded to any type of motion
      equivalently. The PIVC contains multisensory convergence of self-motion cues with
      external visual object motion information, such that neurons do not represent a
      specific transformation of any one sensory input. Instead, the PIVC neuron
      population may define the movement of head, body, and external visual objects in
      space and relative to one another. This comparison of self and external movement
      is consistent with insular cortex functions related to monitoring and explains
      many disparate findings of previous studies. 

PMID- 24671535
TI  - Alignment of sound localization cues in the nucleus of the brachium of the
      inferior colliculus.
AB  - Accurate sound localization is based on three acoustic cues (interaural time and
      intensity difference and spectral cues from directional filtering by the pinna).
      In natural listening conditions, every spatial position of a sound source
      provides a unique combination of these three cues in "natural alignment."
      Although neurons in the central nucleus (ICC) of the inferior colliculus (IC) are
      sensitive to multiple cues, they do not favor their natural spatial alignment. We
      tested for sensitivity to cue alignment in the nucleus of the brachium of the IC
      (BIN) in unanesthetized marmoset monkeys. The BIN receives its predominant
      auditory input from ICC and projects to the topographic auditory space map in the
      superior colliculus. Sound localization cues measured in each monkey were used to
      synthesize broadband stimuli with aligned and misaligned cues; spike responses to
      these stimuli were recorded in the BIN. We computed mutual information (MI)
      between the set of spike rates and the stimuli containing either aligned or
      misaligned cues. The results can be summarized as follows: 1) BIN neurons encode
      more information about auditory space when cues are aligned compared with
      misaligned. 2) Significantly more units prefer aligned cues in the BIN than in
      ICC. 3) An additive model based on summing the responses to stimuli with the
      localization cues varying individually accurately predicts the alignment
      preference with all cues varying. Overall, the results suggest that the BIN is
      the first site in the ascending mammalian auditory system that is tuned to
      natural combinations of sound localization cues. 

PMID- 24671536
TI  - Motor cortical disinhibition with baroreceptor unloading induced by orthostatic
      stress.
AB  - Unloading of the baroreceptors due to orthostatic stress increases corticospinal
      excitability. The purpose of this study was to examine the effects of
      baroreceptor unloading due to orthostatic stress on intracortical excitatory and
      inhibitory pathways in the motor cortex. With transcranial magnetic stimulation,
      measures of intracortical excitability for a hand muscle were tested on 2 days in
      healthy young adults. Lower body negative pressure (LBNP) of 40 mmHg was applied
      during one of the days and not during the Control day. During application of LBNP
      heart rate and the low-frequency component of heart rate variability increased,
      while mean arterial blood pressure was maintained. In the resting state, LBNP
      decreased short-interval intracortical inhibition (SICI) and had no effect on
      intracortical facilitation (ICF) or short-interval intracortical facilitation
      (SICF) compared with the Control day. During isometric contraction, no effects of
      LBNP were observed on tested measures of intracortical excitability including
      SICI, SICF, and cortical silent period. It was concluded that baroreceptor
      unloading due to orthostatic stress results in diminished intracortical
      inhibition, at least in the resting muscle. 

PMID- 24671537
TI  - Simultaneous adaptation of the thumb and index finger of the same hand to
      opposite prism displacements.
AB  - It only takes a few goal-directed hand movements to adapt one's movements to a
      prism-induced displacement of the visual scene. Adaptation to the displacement
      leads to errors in the opposite direction from the initial displacement when the
      prisms are removed. Such aftereffects are thought to arise from some form of
      spatial realignment of the senses or from motor learning. Here, we show that
      humans can simultaneously adapt the movements of the thumb and index finger of
      the same hand to opposing visual displacements. Neither the felt position of the
      hand nor the visually perceived direction can change in two opposite directions
      at the same time, ruling out an explanation based on realignment of the senses.
      It is conceivable that one could learn to adjust the movements differently for
      the two digits despite the fact that both adjustments would involve the same
      hand, but such motor learning should not transfer to matching the position of the
      unseen digit. As transfer was observed when visually matching the position of the
      unseen digit, motor learning cannot explain all of the results. An explanation
      involving supplementing proprioception with a memory-based visual estimate of the
      position of each unseen digit could explain all of the results. Irrespective of
      the mechanism, we can conclude that it is possible to adapt the perceived
      locations of the unseen digits without influencing proprioception. 

PMID- 24671538
TI  - Combining d-cycloserine with motor training does not result in improved general
      motor learning in neurologically intact people or in people with stroke.
AB  - Neurological rehabilitation involving motor training has resulted in clinically
      meaningful improvements in function but is unable to eliminate many of the
      impairments associated with neurological injury. Thus there is a growing need for
      interventions that facilitate motor learning during rehabilitation therapy, to
      optimize recovery. d-Cycloserine (DCS), a partial N-methyl-d-aspartate (NMDA)
      receptor agonist that enhances neurotransmission throughout the central nervous
      system (Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E,
      Hodges L, Davis M. Arch Gen Psychiatry 61: 1136-1144, 2004), has been shown to
      facilitate declarative and emotional learning. We therefore tested whether
      combining DCS with motor training facilitates motor learning after stroke in a
      series of two experiments. Forty-one healthy adults participated in experiment I,
      and twenty adults with stroke participated in experiment II of this two-session,
      double-blind study. Session one consisted of baseline assessment, subject
      randomization, and oral administration of DCS or placebo (250 mg). Subjects then
      participated in training on a balancing task, a simulated feeding task, and a
      cognitive task. Subjects returned 1-3 days later for posttest assessment. We
      found that all subjects had improved performance from pretest to posttest on the
      balancing task, the simulated feeding task, and the cognitive task. Subjects who
      were given DCS before motor training, however, did not show enhanced learning on
      the balancing task, the simulated feeding task, or the associative recognition
      task compared with subjects given placebo. Moreover, training on the balancing
      task did not generalize to a similar, untrained balance task. Our findings
      suggest that DCS does not enhance motor learning or motor skill generalization in
      neurologically intact adults or in adults with stroke. 

PMID- 24671539
TI  - Task-dependent control of the jaw during food splitting in humans.
AB  - Although splitting of food items between the incisors often requires high bite
      forces, rarely do the teeth harmfully collide when the jaw quickly closes after
      split. Previous studies indicate that the force-velocity relationship of the jaw
      closing muscles principally explains the prompt dissipation of jaw closing force.
      Here, we asked whether people could regulate the dissipation of jaw closing force
      during food splitting. We hypothesized that such regulation might be implemented
      via differential recruitment of masseter muscle portions situated along the
      anteroposterior axis because these portions will experience a different
      shortening velocity during jaw closure. Study participants performed two
      different tasks when holding a peanut-half stacked on a chocolate piece between
      their incisors. In one task, they were asked to split the peanut-half only
      (single-split trials) and, in the other, to split both the peanut and the
      chocolate in one action (double-split trials). In double-split trials following
      the peanut split, the intensity of the tooth impact on the chocolate piece was on
      average 2.5 times greater than in single-split trials, indicating a substantially
      greater loss of jaw closing force in the single-split trials. We conclude that
      control of jaw closing force dissipation following food splitting depends on task
      demands. Consistent with our hypothesis, converging neurophysiological and
      morphometric data indicated that this control involved a differential activation
      of the jaw closing masseter muscle along the anteroposterior axis. These latter
      findings suggest that the regulation of jaw closing force after sudden unloading
      of the jaw exploits masseter muscle compartmentalization. 

PMID- 24671540
TI  - Oxygen and seizure dynamics: II. Computational modeling.
AB  - Electrophysiological recordings show intense neuronal firing during epileptic
      seizures leading to enhanced energy consumption. However, the relationship
      between oxygen metabolism and seizure patterns has not been well studied. Recent
      studies have developed fast and quantitative techniques to measure oxygen
      microdomain concentration during seizure events. In this article, we develop a
      biophysical model that accounts for these experimental observations. The model is
      an extension of the Hodgkin-Huxley formalism and includes the neuronal
      microenvironment dynamics of sodium, potassium, and oxygen concentrations. Our
      model accounts for metabolic energy consumption during and following seizure
      events. We can further account for the experimental observation that hypoxia can
      induce seizures, with seizures occurring only within a narrow range of tissue
      oxygen pressure. We also reproduce the interplay between excitatory and
      inhibitory neurons seen in experiments, accounting for the different oxygen
      levels observed during seizures in excitatory vs. inhibitory cell layers. Our
      findings offer a more comprehensive understanding of the complex
      interrelationship among seizures, ion dynamics, and energy metabolism. 

PMID- 24671542
TI  - Organization of local horizontal functional interactions between neurons in the
      inferior temporal cortex of macaque monkeys.
AB  - Detailed knowledge of neuronal circuitry is necessary for understanding the
      mechanisms underlying information processing in the brain. We investigated the
      organization of horizontal functional interactions in the inferior temporal
      cortex of macaque monkeys, which plays important roles in visual object
      recognition. Neuronal activity was recorded from the inferior temporal cortex
      using an array of eight tetrodes, with spatial separation between paired neurons
      up to 1.4 mm. We evaluated functional interactions on a time scale of
      milliseconds using cross-correlation analysis of neuronal activity of the paired
      neurons. Visual response properties of neurons were evaluated using responses to
      a set of 100 visual stimuli. Adjacent neuron pairs tended to show strong
      functional interactions compared with more distant neuron pairs, and neurons with
      similar stimulus preferences tended to show stronger functional interactions than
      neurons with different stimulus preferences. Thus horizontal functional
      interactions in the inferior temporal cortex appear to be organized according to
      both cortical distances and similarity in stimulus preference between neurons.
      Furthermore, the relationship between strength of functional interactions and
      similarity in stimulus preference observed in distant neuron pairs was more
      prominent than in adjacent pairs. The results suggest that functional circuitry
      is specifically organized, depending on the horizontal distances between neurons.
      Such specificity endows each circuit with unique functions. 

PMID- 24671543
TI  - Contrasting the roles of the supplementary and frontal eye fields in ocular
      decision making.
AB  - Single-unit recording in monkeys and functional imaging of the human frontal lobe
      indicate that the supplementary eye field (SEF) and the frontal eye field (FEF)
      are involved in ocular decision making. To test whether these structures have
      distinct roles in decision making, single-neuron activity was recorded from each
      structure while monkeys executed an ocular go/nogo task. The task rule is to
      pursue a moving target if it intersects a visible square or "go zone." We found
      that most SEF neurons showed differential go/nogo activity during the delay
      period, before the target intersected the go zone (delay period), whereas most
      FEF neurons did so after target intersection, during the period in which the
      movement was executed (movement period). Choice probability (CP) for SEF neurons
      was high in the delay period but decreased in the movement period, whereas for
      FEF neurons it was low in the delay period and increased in the movement period.
      Directional selectivity of SEF neurons was low throughout the trial, whereas that
      of FEF neurons was highest in the delay period, decreasing later in the trial.
      Increasing task difficulty led to later discrimination between go and nogo in
      both structures and lower CP in the SEF, but it did not affect CP in the FEF. The
      results suggest that the SEF interprets the task rule early but is less involved
      in executing the motor decision than is the FEF and that these two areas
      collaborate dynamically to execute ocular decisions. 

PMID- 24671541
TI  - Phase maintenance in a rhythmic motor pattern during temperature changes in vivo.
AB  - Central-pattern-generating neural circuits function reliably throughout an
      animal's life, despite constant molecular turnover and environmental
      perturbations. Fluctuations in temperature pose a problem to the nervous systems
      of poikilotherms because their body temperature follows the ambient temperature,
      thus affecting the temperature-dependent dynamics of various subcellular
      components that constitute neuronal circuits. In the crustacean stomatogastric
      nervous system, the pyloric circuit produces a triphasic rhythm comprising the
      output of the pyloric dilator, lateral pyloric, and pyloric constrictor neurons.
      In vitro, the phase relationships of these neurons are maintained over a fourfold
      change in pyloric frequency as temperature increases from 7 degrees C to 23
      degrees C. To determine whether these temperature effects are also found in
      intact crabs, in the presence of sensory feedback and neuromodulator-rich
      environments, we measured the temperature dependence of the pyloric frequency and
      phases in vivo by implanting extracellular electrodes into Cancer borealis and
      Cancer pagurus and shifting tank water temperature from 11 degrees C to 26
      degrees C. Pyloric frequency in the intact crab increased significantly with
      temperature (Q10 = 2-2.5), while pyloric phases were generally conserved. For a
      subset of the C. borealis experiments, animals were subsequently dissected and
      the stomatogastric ganglion subjected to a similar temperature ramp in vitro. We
      found that the maximal frequency attained at high temperatures in vivo is lower
      than it is under in vitro conditions. Our results demonstrate that, over a wide
      temperature range, the phases of the pyloric rhythm in vivo are generally
      preserved, but that the frequency range is more restricted than it is in vitro. 

PMID- 24671544
TI  - Long-latency, inhibitory spinal pathway to ankle flexors activated by homonymous
      group 1 afferents.
AB  - Inhibitory feedback from sensory pathways is important for controlling movement.
      Here, we characterize, for the first time, a long-latency, inhibitory spinal
      pathway to ankle flexors that is activated by low-threshold homonymous afferents.
      To examine this inhibitory pathway in uninjured, healthy participants, we
      suppressed motor-evoked potentials (MEPs), produced in the tibialis anterior
      (TA), by a prior stimulation to the homonymous common peroneal nerve (CPN). The
      TA MEP was suppressed by a triple-pulse stimulation to the CPN, applied 40, 50,
      and 60 ms earlier and at intensities of 0.5-0.7 times motor threshold (average
      suppression of test MEP was 33%). Whereas the triple-pulse stimulation was below
      M-wave and H-reflex threshold, it produced a long-latency inhibition of
      background muscle activity, approximately 65-115 ms after the CPN stimulation, a
      time period that overlapped with the test MEP. However, not all of the MEP
      suppression could be accounted for by this decrease in background muscle
      activity. Evoked responses from direct activation of the corticospinal tract, at
      the level of the brain stem or thoracic spinal cord, were also suppressed by low
      threshold CPN stimulation. Our findings suggest that low-threshold muscle and
      cutaneous afferents from the CPN activate a long-latency, homonymous spinal
      inhibitory pathway to TA motoneurons. We propose that inhibitory feedback from
      spinal networks, activated by low-threshold homonymous afferents, helps regulate
      the activation of flexor motoneurons by the corticospinal tract. 

PMID- 24671545
TI  - Minimally invasive video-assisted thyroidectomy: tips and pearls for the surgical
      technique.
AB  - BACKGROUND: The objectives of this study were first to show principles of the
      minimally invasive video-assisted thyroidectomy (MIVAT), based on a video
      highlighting critical steps, and second to discuss tips and pearls to assist
      surgical teams that would like to start using this technique. METHODS: Based on a
      video, we described tips and pearls of a MIVAT. RESULTS: MIVAT includes 5 main
      steps: (1) skin incision and identification of the common carotid artery, (2)
      dissection and ligation of the upper pedicle, (3) identification of the inferior
      laryngeal nerve and parathyroid glands, (4) isthmectomy and lobe extraction, and
      (5) closure. DISCUSSION: Coordination between the surgeon and the 2 assistants is
      of paramount importance for the performance of MIVAT. Appropriate material is
      also required. The magnification and tissue contrast emphasizes the
      identification of the vessels, the superior and inferior laryngeal nerves, and
      parathyroid glands, on a large-view screen.

PMID- 24671546
TI  - The effect of different angiolytic lasers on resolution of subepithelial mucosal
      hematoma in an animal model.
AB  - OBJECTIVE: Vocal fold hematoma is traditionally managed with a period of voice
      rest, in the order of weeks, to allow natural resolution. This study is designed
      to examine the efficacy and safety of a number of hemoglobin-avid (vascular)
      lasers when used in the setting of acute vocal fold hematoma. METHODS: Venous
      blood drawn from 4 white rabbits was used to create an array of subepithelial
      hematomas in the buccal cavities of each animal. Laser energy from I of 3
      different lasers (532-nm pulsed potassium titanyl phosphate [KTP], 532-nm diode
      KTP, and 940-nm diode laser) was applied to each of the test hematomas at varying
      energy levels. Hematoma sites were photographed at days 0, 1, 5, 7, 9, and 12.
      Two animals were sacrificed on day 7 and the remainder on day 12. Histological
      evaluation of collateral tissue damage and residual hematoma was performed on
      biopsy specimens. RESULTS: Macroscopic and microscopic ulceration at laser
      treated sites was mostly resolved by day 7. Inflammatory cell infiltrate was
      present in laser-treated and hematoma-only sites. Laser-treated samples showed
      alterations in vascularity. CONCLUSION: Hemoglobin-avid lasers may be beneficial
      in accelerating subepithelial hematoma resolution with a favorable tissue damage
      profile.

PMID- 24671547
TI  - Nasopharyngeal acid reflux and Eustachian tube dysfunction in adults.
AB  - OBJECTIVE: This study aimed to evaluate the relationship between nasopharyngeal
      pH and Eustachian tube dysfunction (ETD) in adults. STUDY DESIGN: Unmatched case
      control study. METHODS: Forty-one subjects, 20 adults with a diagnosis of ETD and
      21 healthy adults as controls, were enrolled from an outpatient clinic. All
      subjects had a Dx-pH probe placed near the torus tubarius in the posterior
      nasopharynx for 24 hours. The pH values were recorded every 0.5 second. Decreases
      in pH were considered as reflux events if the pH dropped below 5.5. RESULTS: The
      average nasopharyngeal pH value was 6.90 (range, 5.33-7.73) in the subjects with
      ETD and 7.07 (range, 5.99-7.94) in the controls. The difference between the 2
      groups was not statistically significant (P = .30). The ETD group, on average,
      had a higher number of nasopharyngeal reflux events (2.3 +/- 1.6 vs 0.8 +/- 1.2,
      respectively; P = .002) and higher reflux finding score (3.6 +/- 2.7 vs 0.4 +/-
      1.4, respectively; P < .00 I) than the control group. CONCLUSION: By using a
      novel pH probe that allows detection of acidity in a nonliquid environment, a
      comparison of nasopharyngeal pH between control patients and those with ETD was
      performed. Eustachian tube dysfunction was more likely to be associated with a
      higher number of nasopharyngeal reflux events and higher reflux finding score.
      Nasopharyngeal reflux may have a role in the pathogenesis of ETD.

PMID- 24671548
TI  - Comparison of hearing results of malleovestibulopexy and total ossicular
      replacement prosthesis for chronic otitis media patients with a mobile stapes
      footplate.
AB  - OBJECTIVE: This study aimed to assess differences in hearing outcomes using the
      malleostapedotomy or malleovestibulopexy (MVP) and total ossicular replacement
      prosthesis (TORP) techniques in chronic otitis media patients with a mobile
      stapes footplate. STUDY DESIGN: Case series with planned data collection.
      SETTING: A university medical center. SUBJECTS AND METHODS: In total, 27 patients
      with chronic otitis media at the Sixth Hospital affiliated with Shanghai Jiao
      Tong University, between January and October 2010, were included. All patients
      had destruction of incus and stapes superstructures and a mobile stapes
      footplate. In all patients, surgery was performed under general anesthesia by a
      retroauricular approach. After the lesions were removed completely, ossicular
      reconstruction was performed using 1 of the techniques. In all patients, pure
      tone audiograms were assessed before and 12 months after surgery. RESULTS:
      Thirteen patients underwent MVP surgery, whereas the other 14 cases received
      traditional TORP surgery. All patients showed improvements in functional hearing
      after surgery. Although the numbers of ears that had closure of the air-bone gap
      within 20 dB in the MVP group were not statistically significantly higher than
      those in the TORP group (Fisher's exact test, P > .05), the average postoperative
      gain of the MVP group was significantly higher than that of the TORP group (t
      test, P < .05). CONCLUSION: Functional hearing in chronic otitis media patients
      with a mobile stapes footplate was better in those who underwent MVP surgery than
      in those who underwent TORP surgery.

PMID- 24671549
TI  - A retrospective study of 113 consecutive cases of surgically treated
      spondylodiscitis patients. A single-center experience.
AB  - BACKGROUND: Recommendations for the operative treatment of spondylodiscitis are
      still a controversial issue. METHODS: A retrospective review identified 113
      consecutive patients who underwent surgical debridement and instrumentation for
      spondylodiscitis between 2006 and 2010 at our department. RESULTS: The mean age
      at presentation was 65 years; 78 patients were male (69 %). Distribution of the
      inflammation was lumbar in 68 (60 %), thoracic in 19 (17 %) and cervical in 20
      (18 %) cases. Six patients (5 %) had two concomitant non-contiguous
      spondylodiscitis foci in different segments of the spine. Epidural abscess was
      found in 33 patients (29 %). One hundred four patients (92 %) had pain.
      Neurological deficit was found in 40 patients (35 %). In the thoracic and lumbar
      cases, dorsal instrumentation alone was considered sufficient in 26 cases;
      additional interbody fusion from the posterior was performed in 44 cases. A 360
      degrees  instrumentation was performed in 22 cases. In the cervical cases, only
      ventral spondylodesis and plating were performed in eight cases, only dorsal
      instrumentation in five and 360 degrees  instrumentation in seven. Postoperative
      intravenous antibiotics were administered for 14.4 +/- 9.3 (mean +/- SD) days
      followed by 3.2 +/- 0.8 (mean +/- SD) months of oral antibiosis. Complete healing
      of the inflammation was achieved in 111 (98 %) cases. Two patients died because
      of septic shock, both with fulminant endocarditis. Pain resolved in all cases.
      Neurological deficits were completely resolved in 20 patients, and 14 patients
      had a partial recovery. CONCLUSION: The results of our retrospective study show
      that surgical treatment of spondylodiscitis with a staged surgical approach (if
      needed) and a short 1-2-week period of intravenous antibiotics followed by 3
      months of oral antibiotics is appropriate for most patients in whom conservative
      treatment has failed or is not advisable. Furthermore, surgical treatment of
      newly diagnosed spondylodiscitis might be recommended as an initial treatment
      option in many cases. Thereby the choice of fusion material (autologous bone,
      titanium, PEEK) seems less important.

PMID- 24671550
TI  - A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection
      against lethal sepsis.
AB  - The environmental Gram-negative encapsulated bacillus Burkholderia pseudomallei
      is the causative agent of melioidosis, a disease associated with high morbidity
      and mortality rates in areas of Southeast Asia and northern Australia in which
      the disease is endemic. B. pseudomallei is also classified as a tier I select
      agent due to the high level of lethality of the bacterium and its innate
      resistance to antibiotics, as well as the lack of an effective vaccine. Gram
      negative bacteria, including B. pseudomallei, secrete outer membrane vesicles
      (OMVs) which are enriched with multiple protein, lipid, and polysaccharide
      antigens. Previously, we demonstrated that immunization with multivalent B.
      pseudomallei-derived OMVs protects highly susceptible BALB/c mice against an
      otherwise lethal aerosol challenge. In this work, we evaluated the protective
      efficacy of OMV immunization against intraperitoneal challenge with a
      heterologous strain because systemic infection with phenotypically diverse
      environmental B. pseudomallei strains poses another hazard and a challenge to
      vaccine development. We demonstrated that B. pseudomallei OMVs derived from
      strain 1026b afforded significant protection against septicemic infection with B.
      pseudomallei strain K96243. OMV immunization induced robust OMV-,
      lipopolysaccharide-, and capsular polysaccharide-specific serum IgG (IgG1, IgG2a,
      and IgG3) and IgM antibody responses. OMV-immune serum promoted bacterial killing
      in vitro, and passive transfer of B. pseudomallei OMV immune sera protected naive
      mice against a subsequent challenge. These results indicate that OMV immunization
      provides antibody-mediated protection against acute, rapidly lethal sepsis in
      mice. B. pseudomallei-derived OMVs may represent an efficacious multivalent
      vaccine strategy against melioidosis.

PMID- 24671551
TI  - Development and use of a serum bactericidal assay using pooled human complement
      to assess responses to a meningococcal group A conjugate vaccine in African
      toddlers.
AB  - A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been
      developed for African countries affected by epidemic meningitis caused by
      Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA)
      assays are used to assess protective immune responses to meningococcal
      vaccination. Human complement (hC') was used in early studies demonstrating
      antibody-mediated protection against disease, but it is difficult to obtain and
      standardize. We developed and evaluated a method for sourcing hC' and then used
      the SBA assay with hC' (hSBA) to measure bactericidal responses to PsA-TT
      vaccination in 12- to 23-month-old African children. Sera with active complement
      from 100 unvaccinated blood donors were tested for intrinsic bactericidal
      activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody
      concentration. Performance criteria and pooling strategies were examined and then
      verified by comparisons of three independently prepared hC' lots in two
      laboratories. hSBA titers of clinical trial sera were then determined using this
      complement sourcing method. Two different functional antibody tests were
      necessary for screening hC'. hSBA titers determined using three independent lots
      of pooled hC' were within expected assay variation among lots and between
      laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than
      meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge
      of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers
      persisted in boosted groups for over a year. Quantifying SBA using pooled hC' is
      feasible and showed that PsA-TT was highly immunogenic in African toddlers.

PMID- 24671552
TI  - Seroprevalence of canine norovirus in 14 European countries.
AB  - To investigate the prevalence of the recently described genogroup VI canine
      noroviruses (CNVs) in dogs in Europe, we tested 510 serum samples from dogs in 14
      European countries for anti-IgG CNV antibodies. Seropositive dogs were found
      throughout Europe. Dogs with antibodies against human noroviruses were also
      found. 

PMID- 24671553
TI  - Antibodies against Mycobacterial proteins as biomarkers for HIV-associated smear
      negative tuberculosis.
AB  - Serology data are limited for patients with sputum smear-negative HIV-associated
      active tuberculosis (TB). We evaluated the serum antibody responses against the
      mycobacterial proteins MPT51, MS, and echA1 and the 38-kDa protein via enzyme
      linked immunosorbent assay (ELISA) in South African (S.A.) HIV-positive (HIV(+))
      smear-negative TB patients (n = 56), U.S. HIV(+) controls with a positive
      tuberculin skin test (TST(+); n = 21), and S.A. HIV-negative (HIV(-)) (n = 18)
      and HIV(+) (n = 24) controls. TB patients had positive antibody reactivity
      against MPT51 (73%), echA1 (59%), MS (36%), and the 38-kDa protein (11%). Little
      reactivity against MPT51 and echA1 was observed in control groups at low risk for
      TB, i.e., S.A. HIV(-) (0% and 6%, respectively), and at moderate risk for TB
      development, i.e., U.S. HIV(+) TST(+) controls (14% and 10%, respectively). By
      contrast, more reactivity was detected in the S.A. HIV(+) control group at higher
      risk for TB (25% and 45%, respectively). Our data hold promise that antibody
      detection against MPT51 and echA1 might have adjunctive value in the detection of
      HIV(+) smear-negative TB and might reflect increasing Mycobacterium tuberculosis
      infection activity in asymptomatic HIV(+) individuals. 

PMID- 24671554
TI  - Activation of innate immune responses by Haemophilus influenzae
      lipooligosaccharide.
AB  - A Gram-negative pathogen Haemophilus influenzae has a truncated endotoxin known
      as lipooligosaccharide (LOS). Recent studies on H. influenzae LOS highlighted its
      structural and compositional implications for bacterial virulence; however, the
      role of LOS in the activation of innate and adaptive immunity is poorly
      understood. THP-1 monocytes were stimulated with either lipopolysaccharide (LPS)
      from Escherichia coli or LOS compounds derived from H. influenzae Eagan, Rd, and
      Rd lic1 lpsA strains. Cell surface expression of key antigen-presenting,
      costimulatory, and adhesion molecules, as well as gene expression of some
      cytokines and pattern recognition receptors, were studied. Eagan and Rd LOS had a
      lower capacity to induce the expression of ICAM-1, CD40, CD58, tumor necrosis
      factor alpha (TNF-alpha), and interleukin-1beta (IL-1beta) compared to LPS. In
      contrast, antigen-presenting (HLA-ABC or HLA-DR) and costimulatory (CD86)
      molecules and NOD2 were similarly upregulated in response to LOS and LPS. LOS
      from a mutant Rd strain (Rd lic1 lpsA) consistently induced higher expression of
      innate immune molecules than the wild-type LOS, suggesting the importance of
      phosphorylcholine and/or oligosaccharide extension in cellular responses to LOS.
      An LOS compound with a strong ability to upregulate antigen-presenting and
      costimulatory molecules combined with a low proinflammatory activity may be
      considered a vaccine candidate to immunize against H. influenzae.

PMID- 24671555
TI  - Varicella and varicella vaccination in South Korea.
AB  - With continuing occurrence of varicella despite increasing vaccine coverage for
      the past 20 years, a case-based study, a case-control study, and an
      immunogenicity and safety study were conducted to address the impact of varicella
      vaccination in South Korea. Varicella patients under the age of 16 years were
      enrolled for the case-based study. For the case-control study, varicella patients
      between 12 months and 15 years of age were enrolled with one control matched for
      each patient. For the immunogenicity and safety study, otherwise healthy children
      from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea).
      Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV)
      antibody was measured before and 6 weeks after immunization. In the case-based
      study, the median age of the patients was 4 years. Among 152 patients between 1
      and 15 years of age, 139 children received varicella vaccine and all had
      breakthrough infections. Clinical courses were not ameliorated in vaccinated
      patients, but more vaccinated patients received outpatient rather than inpatient
      care. In the case-control study, the adjusted overall effectiveness of varicella
      vaccination was 54%. In the immunogenicity and safety study, the seroconversion
      rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with
      increasing varicella vaccine uptake, we illustrate no upward age shift in the
      peak incidence, a high proportion of breakthrough disease, almost no amelioration
      in disease presentation by vaccination, and insufficient immunogenicity of
      domestic varicella vaccine. There is need to improve the varicella vaccine used
      in South Korea.

PMID- 24671556
TI  - Salmonella enterica serovar enteritidis ghosts carrying the Escherichia coli heat
      labile enterotoxin B subunit are capable of inducing enhanced protective immune
      responses.
AB  - The Escherichia coli heat-labile enterotoxin B subunit (LTB) is a potent vaccine
      adjuvant. Salmonella enterica serovar Enteritidis ghosts carrying LTB (S.
      Enteritidis-LTB ghosts) were genetically constructed using a novel plasmid,
      pJHL187-LTB, designed for the coexpression of the LTB and E lysis proteins. S.
      Enteritidis-LTB ghosts were characterized using scanning electron microscopy to
      visualize their transmembrane tunnel structures. The expression of LTB in S.
      Enteritidis-LTB ghost preparations was confirmed by immunoblot and enzyme-linked
      immunosorbent assays. The parenteral adjuvant activity of LTB was demonstrated by
      immunizing chickens with either S. Enteritidis-LTB ghosts or S. Enteritidis
      ghosts. Chickens were intramuscularly primed at 5 weeks of age and subsequently
      boosted at 8 weeks of age. In total, 60 chickens were equally divided into three
      groups (n = 20 for each): group A, nonvaccinated control; group B, immunized with
      S. Enteritidis-LTB ghosts; and group C, immunized with S. Enteritidis ghosts.
      Compared with the nonimmunized chickens (group A), the immunized chickens (groups
      B and C) exhibited increased titers of plasma IgG and intestinal secretory IgA
      antibodies. The CD3(+) CD4(+) subpopulation of T cells was also significantly
      increased in both immunized groups. Among the immunized chickens, those in group
      B exhibited significantly increased titers of specific plasma IgG and intestinal
      secretory IgA (sIgA) antibodies compared with those in group C, indicating the
      immunomodulatory effects of the LTB adjuvant. Furthermore, both immunized groups
      exhibited decreased bacterial loads in their feces and internal organs. These
      results indicate that parenteral immunization with S. Enteritidis-LTB ghosts can
      stimulate superior induction of systemic and mucosal immune responses compared to
      immunization with S. Enteritidis ghosts alone, thus conferring efficient
      protection against salmonellosis. 

PMID- 24671557
TI  - Performance of a cytomegalovirus IgG enzyme immunoassay kit modified to measure
      avidity.
AB  - The measurement of cytomegalovirus (CMV) IgG avidity accurately discriminates
      recent and past CMV infections. We sought to determine if the Wampole
      Laboratories CMV IgG enzyme immunoassay (EIA) could be modified to measure
      avidity. The evaluation panel consisted of 156 serum samples we used in 2002 to
      validate a laboratory-developed EIA, in which 78 serum samples exhibited low
      avidity, 7 exhibited intermediate avidity, and 71 exhibited high avidity. The
      qualitative agreement between the two avidity assays was 94% (147/156); all 9
      sera with discordant results exhibited intermediate avidity in one of the assays.
      The avidity index (AI) values in the two assays showed excellent correlation (r =
      0.96, P < 0.0001). The definition of high avidity was verified for the Wampole
      assay by demonstrating high avidity in 91/93 (98%) recently collected CMV IgG
      positive/IgM-negative serum samples. The performance of the Wampole avidity assay
      in a reference laboratory setting was assessed using 470 consecutive serum
      samples submitted for CMV IgG avidity testing. Surprisingly, 101 serum samples
      were negative when screened for CMV IgG using the Wampole kit per the package
      insert; 98 of these 101 serum samples were tested using a CMV IgG
      chemiluminescent immunoassay, and only 5 were positive. Of the 369 CMV IgG
      positive samples, 6% exhibited low IgG avidity, 6% exhibited intermediate
      avidity, and 88% exhibited high avidity; CMV IgM detection rates were inversely
      related to AI levels. These findings show that (i) the Wampole CMV IgG EIA can be
      modified to measure CMV IgG avidity, (ii) many samples are apparently submitted
      for avidity testing without knowledge of their CMV IgG status, and (iii) most CMV
      IgG-positive sera submitted for avidity testing exhibit high avidity. 

PMID- 24671558
TI  - Potential impact of different cytomegalovirus (CMV) IgM assays on an algorithm
      requiring IgM reactivity as a criterion for measuring CMV IgG avidity.
AB  - The measurement of cytomegalovirus (CMV) IgG avidity is a powerful tool for
      identifying individuals with recent CMV infection. Because such patients are
      expected to be positive for CMV IgM, several investigators have suggested that
      CMV IgG-positive sera first be screened for CMV IgM and then only the IgM
      reactive sera be tested for avidity. We investigated the impact of different CMV
      IgM assays on such a reflexing algorithm using a panel of 369 consecutive IgG
      positive serum samples submitted for avidity testing. A bead-based
      immunofluorescent assay (BIFA) identified 105 IgM-positive serum samples, whereas
      an IgM-capture enzyme immunoassay (EIA) identified 48 IgM-positive serum samples;
      this marked difference led us to evaluate additional CMV IgM assays. An enzyme
      linked immunofluorescent assay (ELFA) and a chemiluminescent immunoassay (CIA)
      were used to test all sera with discordant BIFA/EIA results, all sera with
      concordant positive results, and selected sera with concordant negative results.
      The findings indicated that the ELFA would identify 74 CMV IgM-positive samples
      and the CIA would identify 64. Of the 23 low-avidity serum samples, 2 were IgM
      negative by BIFA, 3 by ELFA and CIA, and 4 by EIA; of the 23 intermediate-avidity
      serum samples, 6 were IgM negative by BIFA, 10 by ELFA, and 15 by EIA and CIA. In
      both these avidity groups, BIFA IgM-negative sera were also negative by the other
      3 assays. These findings demonstrate that an algorithm requiring CMV IgM
      reactivity as a criterion for CMV IgG avidity testing does not identify all low
      avidity sera and thus misses some cases of acute CMV infection. 

PMID- 24671559
TI  - Heavy metals levels in fish from aquaculture farms and risk assessment in Lhasa,
      Tibetan Autonomous Region of China.
AB  - Fish is consumed as a common food by humans due to its nutritional and
      therapeutic benefits. However, they can accumulate toxic chemicals (such as heavy
      metals, persistent organic pollutants) from water and food chain. Very few
      studies have been investigated on heavy metal contents in fish from Tibetan
      Autonomous Region of China. In order to study heavy metals levels in fish from
      aquaculture farms and evaluate the risk that human consume fish in this area, we
      collected four types of aquaculture fish species (6 big-head carps, 5 grass
      carps, 5 carps and 5 tilapias) from fisheries around Lhasa city in this study. 9
      heavy metals (Cr, As, Cd, Pb, Cu, Ba, Co, Mn and V) in different tissues of fish
      were determined by an inductively coupled plasma mass spectrometer. Cr, Ba, Co,
      Mn and V could easily accumulate in the gill, and Cu was detected in the hearts
      of all the fishes. Toxic metal (As, Cd and Pb) contents were higher in the liver
      than those in other tissues, heavy metal levels were the lowest in the muscle
      among all tissues. Most of heavy metal concentrations in the tilapia tissues were
      higher than those in other fish tissues, especially arsenic. Arsenic content in
      the tilapia samples was ~2-4 times higher than the maximum levels (MLs) of
      contaminants in the national standard, and other metals were all lower than the
      MLs. Compared the estimated daily intake of heavy metals through fish consumption
      with tolerable daily intakes recommended by FAO, the metals daily intake of As,
      Cd and Pb from fish consumption might not pose serious health risk to the local
      inhabitants. It is therefore necessary to determine the dose level for human,
      which is considered to be taken daily over a lifetime without adverse effects. 

PMID- 24671560
TI  - Year-round behaviour of soil microarthropod communities under plant protection
      product application.
AB  - The use of plant protection products (PPPs) in agro-environments can lead to
      undesired exposure of non-target organisms in non-target compartments. A year
      round field survey was conducted in a vineyard in Northern Italy, for monitoring
      the changes in the structure of soil microarthropod communities under the
      application of PPPs, focusing on springtails and mites, both inside and 4 and 10
      m outside the vineyard. Exposure to PPPs was estimated as time-weighted average
      soil concentrations. The fluctuations in the abundances of the different
      organisms after the application of PPPs, especially insecticides, were recorded.
      A recovery in abundances was observed at the end of the productive season outside
      the field and at the beginning of the next spring within the vineyard. Using
      multivariate statistical tools, the behaviour of each taxon in relation to the
      stressors was assessed. Some organisms were affected by the stressors, while
      others were favoured because of low vulnerability to PPPs and the indirect effect
      of the absence of other taxa. The principal response curves (PRC) method was the
      most sensitive tool for assessing PPP effects on soil arthropod communities.
      Strong differences were evident in the structure of the communities inside and
      outside the vineyard, with the communities sampled 4 and 10 m outside the
      vineyard being fairly similar, the latter considered as control. The role of
      physical stressors on community composition is recognised. However, chemical
      stressors, and in particular PPP exposure seemed to have larger effects on
      structural and functional characteristics of soil arthropod communities than
      physical stressors.

PMID- 24671561
TI  - Grading of shoulder ulcerations in sows by biopsies.
AB  - Shoulder ulcerations can be graded postmortem from 0 to 4 on a pathoanatomical
      scale. However, veterinarians and farmers express difficulties evaluating the
      grade of the lesions antemortem. Accurate grading is needed in order to comply
      with veterinary instruction in relation to the Danish legislation, stating that
      sows with shoulder ulcers grade 3 or 4 must be kept loose and have access to soft
      bedding. Thus, the aim of the present study was to evaluate if biopsies from the
      center of a shoulder ulcer can be used to point out animals for which an
      intervention must be initiated. Postmortem, a punch biopsy was sampled from the
      center of the ulceration or from the tissue overlaying the tuber spina scapula.
      Afterward, the shoulders were cross-sectioned and evaluated grossly and
      histologically ("gold standard"). In total, 121 shoulders were included in the
      study, and the diagnostic value of a punch biopsy in grading shoulder ulcerations
      was evaluated. The results showed a sensitivity of 0.78, a specificity of 0.98, a
      positive likelihood ratio of 38.36, and a negative likelihood ratio of 0.22. The
      agreement between the cross-section evaluation and the punch biopsy was found to
      be 0.90 by calculating the Cohen kappa value. In conclusion, a single punch
      biopsy from the center of an ulcer is useful for determining the grade of a
      shoulder ulcer and can be used to facilitate the identification of sows with
      ulcers requiring an intervention. 

PMID- 24671564
TI  - Tunable electroluminescence properties in CdSe/PVK guest-host based light
      emitting devices.
AB  - The photo- (PL) and electroluminescence (EL) properties of CdSe-TOPO quantum dots
      (QDs) doped into a PVK:PBD host matrix with a double-layer device configuration
      [PEDOT:PSS/PVK:PBD/QDs/LiF/Al] are investigated. Depending on the concentrations
      of CdSe-TOPO QDs, EL properties are changed including the emitted colors. At a
      low QD concentration (1 wt%), QD-light emitting diode (QD-LED) shows a broad EL
      band with dominant QD emission and minor emissions (electromer from PVK and
      exciplex from the PVK:PBD blend). However, at a higher QD concentration (5 wt%)
      there are two competitive emission peaks observed in the EL spectrum, arising
      from exciplex emission in the PVK:PBD blend (shorter wavelength) and QD emission
      at CdSe-TOPO. These EL peaks are closely related to Forster energy transfer and
      charge transfer, respectively. With increasing bias voltage, the EL peak at
      shorter wavelength gradually decreases and the emitted color is changed from blue
      to dark green in the QD-LED. As a result, both the concentration and applied bias
      voltage are important tunable factors in the emitted colors. 

PMID- 24671562
TI  - Changes in vertebral strain energy correlate with increased presence of Schmorl's
      nodes in multi-level lumbar disk degeneration.
AB  - Patients with skipped-level disk degeneration (SLDD) were recently reported as
      having a higher prevalence of Schmorl's nodes than patients with contiguous multi
      level disk degeneration (CMDD). Fourteen versions of a nonlinear finite element
      model of a lumbar spine, representing different patterns of single and multi
      level disk degeneration, were simulated under physiological loading. Results show
      that vertebral strain energy is a possible predictor in the development of
      Schmorl's nodes. The analysis also shows evidence that the development of
      Schmorl's nodes may be highly dependent on the location of the degeneration disk,
      with a higher prevalence at superior levels of the lumbar spine. 

PMID- 24671565
TI  - Isolation and purification of condensed tannins from flamboyant tree and their
      antioxidant and antityrosinase activities.
AB  - Flamboyant tree, a kind of medicinal plant, was studied as a source of condensed
      tannins. The antioxidant activities of the condensed tannins from the leaf,
      fruit, and stem bark of flamboyant tree were screened by ABTS radical and
      hydroxyl radical scavenging activity methods. The results indicated that these
      compounds possessed potent antioxidant activity. Their structures were then
      characterized by high-performance liquid chromatography-electrospray ionization
      mass spectrometry (HPLC-ESI-MS) after thiolytic degradation. The results showed
      that the leaf condensed tannins were composed of afzelechin/epiafzelechin,
      catechin/epicatechin, and gallocatechin/epigallocatechin, while the fruit and
      stem bark condensed tannins had afzelechin/epiafzelechin and
      catechin/epicatechin. In addition, the condensed tannins were evaluated for their
      antityrosinase ability. They were found to have significant antityrosinase
      activity. The IC50 values were 35 +/- 2.0 and 40 +/- 0.5 MUg/ml for the condensed
      tannins of fruit and stem bark, respectively. Further, fluorescence quenching and
      copper interacting techniques were utilized to unravel the molecular mechanisms
      of the inhibition. The results showed that the hydroxyl group of the condensed
      tannins could chelate the dicopper center of the enzyme and interact with
      tryptophan residues. Our studies revealed that condensed tannins might be
      suitable for use in food, agriculture, cosmetic, nutraceutical, and
      pharmaceutical applications. 

PMID- 24671566
TI  - Municipal solid waste landfill leachate treatment and electricity production
      using microbial fuel cells.
AB  - Microbial fuel cells were designed and operated to treat landfill leachate while
      simultaneously producing electricity. Two designs were tested in batch cycles
      using landfill leachate as a substrate without inoculation (908 to 3,200 mg/L
      chemical oxygen demand (COD)): Circle (934 mL) and large-scale microbial fuel
      cells (MFC) (18.3 L). A total of seven cycles were completed for the Circle MFC
      and two cycles for the larger-scale MFC. Maximum power densities of 24 to 31
      mW/m(2) (653 to 824 mW/m(3)) were achieved using the Circle MFC, and a maximum
      voltage of 635 mV was produced using the larger-scale MFC. In the Circle MFC,
      COD, biological oxygen demand (BOD), total organic carbon (TOC), and ammonia were
      removed at an average of 16%, 62%, 23%, and 20%, respectively. The larger-scale
      MFC achieved an average of 74% BOD removal, 27% TOC removal, and 25% ammonia
      reduction while operating over 52 days. Analysis of the microbial characteristics
      of the leachate indicates that there might be both supportive and inhibiting
      bacteria in landfill leachate for operation of an MFC. Issues related to scale-up
      and heterogeneity of a mixed substrate remain.

PMID- 24671567
TI  - Processing of beta-glucosidase-silk fibroin nanoparticle bioconjugates and their
      characteristics.
AB  - Silk fibroin derived from Bombyx mori is a biomacromolecular protein with
      excellent biocompatibility. The aim of this work was to develop silk fibroin
      nanoparticles (SFNs) derived from the fibrous protein, which is a novel vector
      for enzyme modification in food processing. Silk fibroin was dissolved in highly
      concentrated CaCl2 and subjected to lengthy desalting in water. The resulting
      liquid silk, which contained water-soluble polypeptides with molecular mass
      ranging from 10 to 200 kDa, and beta-glucosidase were added rapidly into acetone.
      The beta-glucosidase molecules were embedded into silk fibroin nanoparticles,
      forming beta-glucosidase-silk fibroin nanoparticles (betaG-SFNs) with a diameter
      of 50-150 nm. The enzyme activity of the betaG-SFN bioconjugates was determined
      with p-nitrophenyl-beta-D-glucoside as the substrate, and the optimum conditions
      for the preparation of betaG-SFNs were investigated. The enzyme activity recovery
      of betaG-SFNs was 59.2 % compared to the free enzyme (specific activity was 1 U
      mg(-1)). The kinetic parameters of the betaG-SFNs and the free beta-glucosidase
      were the same. The betaG-SFNs had good operational stability and could be used
      repeatedly. These results confirmed that silk protein nanoparticles were good
      carriers as bioconjugates for the modification of enzymes with potential value
      for research and development. The method used in this study has potential
      applications in food processing and the production of flavour agents.

PMID- 24671568
TI  - Amino acid supplementation enhances urokinase production by HT-1080 cells.
AB  - Medium optimization is an important strategy that can lead to several fold
      increase in the production of proteins in cell culture. However, the usual
      methods of medium optimization are complex and time consuming. Urokinase is a
      widely employed thrombolytic drug for the treatment of stroke. We describe here
      medium optimization for maximizing urokinase production by HT-1080 cells using
      supplementation of specific amino acids. The new specifically designed method
      resulted in 240 % increase in urokinase productivity.

PMID- 24671569
TI  - Modification of glycolysis and its effect on the production of L-threonine in
      Escherichia coli.
AB  - High concentrations of acetate, the main by-product of Escherichia coli (E. coli)
      high cell density culture, inhibit bacterial growth and L-threonine production.
      Since metabolic overflux causes acetate accumulation, we attempted to reduce
      acetate production by redirecting glycolysis flux to the pentose phosphate
      pathway by deleting the genes encoding phosphofructokinase (pfk) and/or pyruvate
      kinase (pyk) in an L-threonine-producing strain of E. coli, THRD. pykF, pykA,
      pfkA, and pfkB deletion mutants produced less acetate (9.44 +/- 0.83, 3.86 +/-
      0.88, 0.30 +/- 0.25, and 6.99 +/- 0.85 g/l, respectively) than wild-type THRD
      cultures (19.75 +/- 0.93 g/l). THRDDeltapykF and THRDDeltapykA produced 11.05 and
      5.35 % more L-threonine, and achieved a 10.91 and 5.60 % higher yield on glucose,
      respectively. While THRDDeltapfkA grew more slowly and produced less L-threonine
      than THRD, THRDDeltapfkB produced levels of L-threonine (102.28 +/- 2.80 g/l) and
      a yield on glucose (0.34 g/g) similar to that of THRD. The dual deletion mutant
      THRDDeltapfkBDeltapykF also achieved low acetate (7.42 +/- 0.81 g/l) and high L
      threonine yields (111.37 +/- 2.71 g/l). The level of NADPH in THRDDeltapfkA
      cultures was depressed, whereas all other mutants produced more NADPH than THRD
      did. These results demonstrated that modification of glycolysis in E. coli THRD
      reduced acetate production and increased accumulation of L-threonine.

PMID- 24671570
TI  - Functional expression of a single-chain antibody fragment against human epidermal
      growth factor receptor 2 (HER2) in Escherichia coli.
AB  - The human epidermal growth factor receptor (HER) family plays an important role
      in cell growth and signaling and alteration of its function has been demonstrated
      in many different kinds of cancer. Receptor dimerization is necessary for the HER
      signal transduction pathway and tyrosine kinase activity. Recently, several
      monoclonal antibodies have been developed to directly interfere with ligand-HER
      receptor binding and receptor dimerization. A single chain variable fragment
      (ScFv) is a valuable alternative to an intact antibody. This report describes the
      production and purification of an ScFv specific for domain II of the HER2
      receptor in Escherichia coli BL21 (DE3) cytoplasm. The majority of expressed of
      anti-her2his-ScFv protein was produced as inclusion bodies. A Ni-NTA affinity
      column was used to purify the anti-her2his-ScFv protein. The molecular weight of
      anti-her2his-ScFv protein was estimated to be approximately 27 kDa, as confirmed
      by SDS-PAGE and Western blotting assay. The anti-her2his-ScFv showed near 95 %
      purity and reached a yield of approximately 29 mg/l in flask fermentation. The
      purified anti-her2his-ScFv showed its biological activity by binding to HER2
      receptor on the surface of BT-474 cells. This ScFv may be a potential
      pharmaceutical candidate for targeting tumour cells overexpressing HER2 receptor.

PMID- 24671571
TI  - Guideline for postmarketing Chinese medicine pharmacoeconomic evaluation.
AB  - Pharmacoeconomics is an important part of the postmarketing Chinese medicine (CM)
      evaluation, and postmarketing pharmacoeconomic evaluation can reveal the clinical
      and market value of CM. The purpose of establishing the guideline for
      pharmacoeconomic evaluation is to make the evaluation process and results
      regarding Chinese patent medicines both scientific and fair. Every country's
      guidelines for pharmacoeconomic evaluation act as reference guidelines, we have
      already drawn up the guideline that takes into account the special
      characteristics of CM; and these are in preparation for the postmarketing CM
      pharmacoeconomic evaluation. 

PMID- 24671572
TI  - State-dependent blocker interactions with the CFTR chloride channel: implications
      for gating the pore.
AB  - Chloride permeation through the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel is subject to voltage-dependent open-channel block
      by a diverse range of cytoplasmic anions. However, in most cases the ability of
      these blocking substances to influence the pore opening and closing process has
      not been reported. In the present work, patch clamp recording was used to
      investigate the state-dependent block of CFTR by cytoplasmic Pt(NO2)4(2-) ions.
      Two major effects of Pt(NO2)4(2-) were identified. First, this anion caused fast,
      voltage-dependent block of open channels, leading to an apparent decrease in
      single-channel current amplitude. Secondly, Pt(NO2)4(2-) also decreased channel
      open probability due to an increase in interburst closed times. Interestingly,
      mutations in the pore that weakened (K95Q) or strengthened (I344K, V345K)
      interactions with Pt(NO2)4(2-) altered blocker effects both on Cl(-) permeation
      and on channel gating, suggesting that both these effects are a consequence of
      Pt(NO2)4(2-) interaction with a single site within the pore. Experiments at
      reduced extracellular Cl(-) concentration hinted that Pt(NO2)4(2-) may have a
      third effect, possibly increasing channel activity by interfering with channel
      closure. These results suggest that Pt(NO2)4(2-) can enter from the cytoplasm
      into the pore inner vestibule of both open and closed CFTR channels, and that
      Pt(NO2)4(2-) bound in the inner vestibule blocks Cl(-) permeation as well as
      interfering with channel opening and, perhaps, channel closure. Implications for
      the location of the channel gate in the pore, and the operation of this gate, are
      discussed.

PMID- 24671575
TI  - Positive affect and cognitive control: approach-motivation intensity influences
      the balance between cognitive flexibility and stability.
AB  - In most prior research, positive affect has been consistently found to promote
      cognitive flexibility. However, the motivational dimensional model of affect
      assumes that the influence of positive affect on cognitive processes is modulated
      by approach-motivation intensity. In the present study, we extended the
      motivational dimensional model to the domain of cognitive control by examining
      the effect of low- versus high-approach-motivated positive affect on the balance
      between cognitive flexibility and stability in an attentional-set-shifting
      paradigm. Results showed that low-approach-motivated positive affect promoted
      cognitive flexibility but also caused higher distractibility, whereas high
      approach-motivated positive affect enhanced perseverance but simultaneously
      reduced distractibility. These results suggest that the balance between cognitive
      flexibility and stability is modulated by the approach-motivation intensity of
      positive affective states. Therefore, it is essential to incorporate motivational
      intensity into studies on the influence of affect on cognitive control. 

PMID- 24671573
TI  - Endocannabinoids produced upon action potential firing evoke a Cl(-) current via
      type-2 cannabinoid receptors in the medial prefrontal cortex.
AB  - The functional presence of type-2 cannabinoid receptors (CB2Rs) in layer II/III
      pyramidal neurons of the rat medial prefrontal cortex (mPFC) was recently
      demonstrated. In the present study, we show that the application of the
      endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and methanandamide [a
      stable analog of the eCB anandamide (AEA)] can activate CB2Rs of mPFC layer
      II/III pyramidal neurons, which subsequently induces a Cl(-) current. In
      addition, we show that action potential (AP) firing evoked by 20-Hz current
      injections results in an eCB-mediated opening of Cl(-) channels via CB2R
      activation. This AP-evoked synthesis of eCBs is dependent on the Ca(2+) influx
      through N-type voltage-gated calcium channels. Our results indicate that 2-AG is
      the main eCB involved in this process. Finally, we demonstrate that under
      physiologically relevant intracellular Cl(-) conditions, 20-Hz AP firing leads to
      a CB2R-dependent reduction in neuronal excitability. Altogether, our data
      indicate that eCBs released upon action potential firing can modulate, through
      CB2R activation, neuronal activity in the mPFC. We discuss how this may be a
      mechanism to prevent excessive neuronal firing.

PMID- 24671576
TI  - Growth performance of immunologically castrated (with Improvest) barrows (with or
      without ractopamine) compared to gilt, physically castrated barrow, and intact
      male pigs.
AB  - The study used a randomized complete block design (blocking factor was date of
      start on test) with 5 treatments: 1) physically castrated barrows (PC), 2) intact
      males (IM), 3) gilts (G), 4) immunologically castrated barrows (IC), and 5)
      immunologically castrated barrows fed ractopamine at 5 mg/kg (IC+RAC). The study
      used 192 pigs and was performed from the 16 wk of age (67.2 +/- 2.52 kg BW) to a
      pen mean BW of 132.5 +/- 3.60 kg. For IC+RAC, ractopamine was fed for the final
      23 d of the study. Pigs were housed in groups of 4 (10 groups for PC, IM, G, and
      IC and 8 groups for IC+RAC) in a finishing building at a floor space of 1.18
      m(2)/pig. Diets were formulated to meet requirements of IM except that the diet
      for the IC+RAC fed during the ractopamine feeding period was formulated to meet
      requirements of pigs on that treatment. Pigs had ad libitum access to feed and
      water throughout the study period and were individually weighed at the start, wk
      2 and 4, and subsequently every week until the end of study. For the overall
      study period, IC had greater (P <= 0.05) ADG than the other genders (1,150,
      1,024, 1,064, and 954 g/d for IC, PC, IM, and G, respectively; SEM = 25.8) and
      required fewer days to reach slaughter weight than the other genders (58.1, 61.6,
      61.6, and 66.5 d for IC, PC, IM, and G, respectively; SEM = 1.26). Overall ADFI
      was less (P <= 0.05) for IM and G than IC and PC, which were similar (P > 0.05)
      in this respect (3.11, 3.06, 2.68, and 2.75 kg/d for IC, PC, IM, and G,
      respectively; SEM = 0.061). Overall G:F was greater (P <= 0.05) for IM than the
      other genders; IC had greater overall G:F than PC and G, which were similar in
      this respect (0.371, 0.335, 0.397, and 0.347 kg/kg for IC, PC, IM, and G,
      respectively; SEM = 0.0068). Immunologically castrated barrows had greater (P <=
      0.05) ADG (30.7%) and ADFI (22.5%) than PC from the second week following the
      second Improvest dose to the end of the study. During the ractopamine feeding
      period, IC+RAC had greater (P <= 0.05) ADG (11.6%) and G:F (17.3%) than IC. The
      results of this study confirmed previously observed gender differences and
      effects of ractopamine on growth performance and that IC grew faster and had
      greater feed efficiency than PC during the study period. 

PMID- 24671578
TI  - Management strategies to improve the performance of low birth weight pigs to
      weaning and their long-term consequences.
AB  - Performance of pigs from birth to slaughter is a result of a complex interaction
      of factors, with the early stages of a pig's life likely to affect lifetime
      performance. During the preweaning stage, piglets are reliant on the sow for
      nutrition, and sibling competition is likely to affect growth, in particular for
      low birth weight (LBiW) piglets. The objective of the experiment was to determine
      the effect of litter composition (littermate weight) and milk supplementation
      during lactation on the performance of LBiW pigs to weaning and the long-term
      consequences of treatment to slaughter. The experiment was a 2 * 2 factorial with
      littermate weight (normal or LBiW) and provision of supplementary milk from d 1
      to 28 (yes or no) as factors. A total of 265 piglets were selected within 24 h of
      birth and cross-fostered to create 2 litter types (LOW = LBiW pigs [<= 1.25 kg]
      only and MX = both LBiW and normal birth weight pigs [1.6 to 2.0 kg]); half of
      the litters within a type were supplemented with milk and the other half were
      not. The behavior of litters given milk was recorded to identify milk consumption
      patterns. Piglets were weaned at d 28 and kept in their litters until d 70 and
      then subsequently housed in mixed groups until slaughter. No difference was
      observed at any stage in the ADG of pigs given access to supplementary milk or
      not (P > 0.05) nor was there any significant interaction between milk provision
      and litter composition (P > 0.05). However, LOW litters drank significantly more
      supplementary milk than MX litters (P < 0.001). There was a significant effect of
      litter type on ADG from d 14 to 28, with LBiW pigs in LOW litters performing
      better than those in MX litters (0.252 versus 0.217 kg/d; P < 0.05). At weaning,
      LBiW piglets in LOW litters weighed over 500 g more than those in MX litters (P <
      0.05). In MX litters there was a significant interaction between birth weight and
      supplementary milk on the CV of BW from d 14 to slaughter (P < 0.05). In
      conclusion, grouping LBiW piglets with similar sized littermates preweaning can
      improve preweaning performance by reducing competition from heavier littermates;
      however, this advantage does not persist after weaning. Although supplementary
      milk does not improve LBiW pig performance before or after weaning, it affects
      their drinking behavior and can reduce the variation in the BW of LBiW piglets in
      mixed litters to slaughter.

PMID- 24671579
TI  - Feed intake, average daily gain, feed efficiency, and real-time ultrasound traits
      in Duroc pigs: I. Genetic parameter estimation and accuracy of genomic
      prediction.
AB  - The efficiency of producing salable products in the pork industry is largely
      determined by costs associated with feed and by the amount and quality of lean
      meat produced. The objectives of this paper were 1) to explore heritability and
      genetic correlations for growth, feed efficiency, and real-time ultrasound traits
      using both pedigree and marker information and 2) to assess accuracy of genomic
      prediction for those traits using Bayes A prediction models in a Duroc terminal
      sire population. Body weight at birth (BW at birth) and weaning (BW at weaning)
      and real-time ultrasound traits, including back fat thickness (BF), muscle depth
      (MD), and intramuscular fat content (IMF), were collected on the basis of farm
      protocol. Individual feed intake and serial BW records of 1,563 boars obtained
      from feed intake recording equipment (FIRE; Osborne Industries Inc., Osborne, KS)
      were edited to obtain growth, feed intake, and feed efficiency traits, including
      ADG, ADFI, feed conversion ratio (FCR), and residual feed intake (RFI).
      Correspondingly, 1,047 boars were genotyped using the Illumina PorcineSNP60
      BeadChip. The remaining 516 boars, as an independent sample, were genotyped with
      a low-density GGP-Porcine BeadChip and imputed to 60K. Magnitudes of heritability
      from pedigree analysis were moderate for growth, feed intake, and ultrasound
      traits (ranging from 0.44 +/- 0.11 for ADG to 0.58 +/- 0.09 for BF); heritability
      estimates were 0.32 +/- 0.09 for FCR but only 0.10 +/- 0.05 for RFI.
      Comparatively, heritability estimates using marker information by Bayes A models
      were about half of those from pedigree analysis, suggesting "missing
      heritability." Moderate positive genetic correlations between growth and feed
      intake (0.32 +/- 0.05) and back fat (0.22 +/- 0.04), as well as negative genetic
      correlations between growth and feed efficiency traits (-0.21 +/- 0.08, -0.05 +/-
      0.07), indicate selection solely on growth traits may lead to an undesirable
      increase in feed intake, back fat, and reduced feed efficiency. Genetic
      correlations among growth, feed intake, and FCR assessed by a multiple-trait
      Bayes A model resulted in increased genetic correlation between ADG and ADFI, a
      negative correlation between ADFI and FCR, and a positive correlation between ADG
      and FCR. Accuracies of genomic prediction for the traits investigated, ranging
      from 9.4% for RFI to 36.5% for BF, were reported that might provide new insight
      into pig breeding and future selection programs using genomic information. 

PMID- 24671580
TI  - Addition of nonstarch polysaccharides degrading enzymes to two hulless barley
      varieties fed in diets for weaned pigs.
AB  - A study was conducted to evaluate the effect of 2 hulless barley varieties, with
      or without the addition of a nonstarch polysaccharide (NSP) enzyme complex (beta
      glucanase and xylanase), on growth performance of weaned piglets in a 42-d
      feeding study. The study was conducted with 140 piglets (PIC * Duroc). Pigs were
      allocated to pens (4 castrated males or 4 females per pen) based on BW and sex,
      and pens were assigned to 5 experimental diets with 4 pens of castrated males and
      3 pens of females per treatment. Five isonitrogenous and isoenergetic diets were
      compared: 1) control corn-based diet (CTR), 2) diet with corn and wheat bran
      replaced by the Astartis hulless barley variety (AS), 3) diet with corn and wheat
      bran replaced by the AS supplemented with the NSP enzyme complex (ASE), 4) diet
      with corn and wheat bran replaced by the Alamo hulless barley variety (AL), and
      5) diet with corn and wheat bran replaced by the AL supplemented with the NSP
      enzyme complex (ALE). The diets were formulated to meet or exceed nutrient
      requirements and offered in 2 phases: d 0 to 14 and d 14 to 42. At the end of the
      study, pigs fed AS and AL had equal weights as pigs fed CTR. Pigs fed the hulless
      barley diets had greater (P < 0.05) ADG during the second phase (P2) and overall
      phase, BW at d 42, and G:F during the P2 than those fed the CTR. Pigs fed the ASE
      and ALE had greater (P < 0.05) ADFI during the P2 and overall ADG than those fed
      the AS and AL. The increases in ADG during the P2 and final BW obtained with NSP
      enzyme supplementation were greater in pigs fed the AS than those fed the AL
      (barley * enzyme, P < 0.05). On the other hand, the NSP enzyme complex increased
      G:F in pigs fed the AS during the P2 and overall phase, but it had no effect on
      those fed the AL (barley * enzyme, P < 0.05). In conclusion, hulless barley with
      or without the NSP enzyme complex can be a replacement ingredient for corn and
      wheat bran in weaned pig diets. Addition of the NSP enzyme complex to AS variety,
      but not AL variety, improved growth performance of weanling pigs. 

PMID- 24671581
TI  - Evaluation of the Criollo breed Romosinuano as purebred and crossbred cows with
      Brahman and Angus in Florida. II. Maternal influence on calf traits, cow weight,
      and measures of maternal efficiency.
AB  - The objectives of this work were to compare the Criollo breed Romosinuano as
      straightbred and crossbred cows with Angus and Brahman in subtropical Florida and
      to estimate heterosis for size traits of their calves, their own weight, and
      maternal efficiency traits. Cows (n = 404) were born from 2002 to 2005. After
      their first exposure to bulls as young cows, crossbred cows were bred to bulls of
      the third breed, and straightbred cows were bred in to bulls of the other 2
      breeds. Calves were spring-born from 2005 through 2011. Evaluated calf (n =
      1,254) traits included birth weight and weight, ADG, BCS, and hip height at
      weaning. Cow weight (n = 1,389) was recorded at weaning. Maternal efficiency
      traits evaluated included weaning weight per 100 kg cow weight, weaning weight
      per calving interval, and weaning weight per cow exposed to breeding (n = 1,442).
      Fixed effects and their interactions were investigated included sire and dam
      breed of cow, sire breed of calf, cow age, year, calf gender, and weaning age as
      a linear covariate (calf traits at weaning). Direct and maternal additive genetic
      effects were random in models for calf traits; only direct additive effects were
      modeled for cow traits. Cows sired by Angus bulls from outside the research herd
      had calves that were heavier at birth and weaning and greater ADG, BCS, and hip
      height (P < 0.05). Estimates of heterosis for weaning weight, BCS, and ADG ranged
      from 1.3 to 13.2% for all pairs of breeds (P < 0.05). Estimates of heterosis for
      birth weight (3.2 to 8.2%) and hip height (2.3%) were significant for Romosinuano
      Angus and Brahman-Angus. Heterosis for cow weight was 65 +/- 8 kg for Brahman
      Angus (P < 0.001), and estimates for other pairs of breeds were approximately one
      half that value. Heterosis for weaning weight/100 kg cow weight was 3.4 +/- 0.75
      kg for Romosinuano-Angus. Heterosis estimates for weaning weight/calving interval
      (P < 0.001) ranged from 0.08 +/- 0.01 to 0.12 +/- 0.01. Heterosis for weaning
      weight/cow exposed were 31.6 7.7, 36.9 +/- 7.4, and 59.1 +/- 7.5 kg for
      Romosinuano-Angus, Romosinuano-Brahman, and Brahman-Angus, respectively (P <
      0.001). Most aspects of Romosinuano crossbred maternal performance were
      acceptable; maternal performance of Brahman-Angus cows excelled. 

PMID- 24671582
TI  - Genomewide study and validation of markers associated with production traits in
      German Landrace boars.
AB  - We present results from a genomewide association study (GWAS) and a single-marker
      association study. The GWAS was performed with the Illumina PorcineSNP60 BeadChip
      from which 5 markers were selected for a validation analysis. Genetic effects
      were estimated for feed intake, weight gain, and traits of fat and muscle tissue
      in German Landrace boars kept on performance test stations. The GWAS was
      performed in a population of 288 boars and the validation study for another 432
      boars. No statistically significant effect was found in the GWAS after adjusting
      for multiple testing. Effects of 2 markers, which were significant genomewide
      before correction for multiple testing (P < 0.00005), could be confirmed in the
      validation study. The major allele of marker ALGA0056781 on SSC1 was positively
      associated with both higher weight gain and fat deposition. The effect on live
      weight gain was 2.25 g/d in the GWAS (P = 0.0003) and 3.73 g/d in the validation
      study (P = 0.01) and for back fat thickness was 0.15 mm in the GWAS (P < 0.0001)
      and 0.20 mm in the validation study (P = 0.02). The marker had similar effects on
      test-day weight gain (GWAS: 3.85 g/d, P = 0.001; validation study: 6.80 g/d, P =
      0.003) and back fat area (GWAS: 0.27 cm(2), P < 0.0001; validation study: 0.35
      cm(2), P = 0.03). Marker ASGA0056782 on SSC13 was associated with live-weight
      gain. The major allele had negative effects in both studies (GWAS: -4.88 g/d, P <
      0.0001; validation study: -3.75 g/d, P = 0.02). The effects of these 2 markers
      would have been excluded based on the GWAS alone but were shown to be
      significantly trait associated in the validation study indicating a false
      negative result. The G protein-coupled receptor 126 (GPR126) gene approximately
      200 kb downstream of marker ALGA0001781 was shown to be associated with human
      height and therefore might explain the association with weight gain in pigs.
      Several traits were affected in an economically desired direction by the minor
      allele of the markers, pointing to the possibility of improvement through further
      selection. 

PMID- 24671583
TI  - Origins and genetic diversity of British cattle breeds in Brazil assessed by
      pedigree analyses.
AB  - Pedigree information available for Angus (ANG), Devon (DEV), Hereford (HER), and
      Shorthorn (SHO) cattle in Brazil was analyzed to appraise the genetic diversity
      and population structure of these breeds. Pedigree records collected from the
      beginning of the 20th century until 2010 were used in the analyses. Over time,
      the number of herdbook registrations declined in HER after a peak in the 1970s,
      remained low in DEV and SHO, and increased steadily in ANG since the 1990s, such
      that it the latter is now the leading British cattle breed in Brazil. The average
      number of offspring registered per sire ranged from about 12 (SHO) to 20 (DEV)
      and the mean generation interval ranged from about 6.0 (HER and SHO) to 6.4 (ANG)
      years. In the reference population (calves born in 2009 and 2010, plus those born
      in 2008 for SHO) the mean equivalent number of generations known ranged from
      about 7 (SHO) to 9 (HER). In the 4 breeds studied, nearly all animals born over
      the last few years are inbred, even though the mean level of inbreeding in the
      reference population is below 4% in all breeds. The rate of inbreeding per
      generation, computed from the individual increase in inbreeding, ranged from
      about 0.2 (ANG) to 0.5% (DEV), with a corresponding effective population size of
      245 and 92, respectively, which is above the recommended minimum critical
      threshold. The number of founders/ancestors contributing with 50% of the
      reference population gene pool was 211/26 for ANG, 41/14 for DEV, 164/25 for HER,
      and 79/10 for SHO, with effective number of founders/ancestors/founder genomes of
      470/68/36, 89/33/16, 289/59/30, and 200/28/18 for ANG, DEV, HER, and SHO,
      respectively. The genetic contribution of different countries to the gene pool of
      each breed indicated that, throughout the period studied, DEV genes originated
      predominantly from the United Kingdom, while for the other breeds there was a
      changing pattern over time. Until the 1970s Argentina was the major supplier of
      ANG, while HER and SHO genes were mostly from Uruguay, but since then the United
      States took the leading role as supplier of ANG, HER, and SHO genes to Brazil.
      Our results reveal a mild increase in inbreeding in all breeds studied, with
      effective population size estimates indicating that reasonable levels of genetic
      diversity have been maintained in all 4 breeds. Continuous monitoring of
      inbreeding trends and of parameters derived from probability of gene origin
      should be ensured to warrant the long-term maintenance of genetic diversity. 

PMID- 24671584
TI  - Importance of grass-legume choices on cattle grazing behavior, performance, and
      meat characteristics.
AB  - We determined if tall fescue in a mixture with either tannin-containing sainfoin
      or saponin-containing alfalfa affected cattle foraging behavior, performance,
      meat quality, and consumer acceptance of meat. Foraging behavior, BW, and pasture
      biomass before and after grazing were monitored when cattle strip-grazed 3
      replications of 2 treatments from May through September 2010 (12
      calves/replication) and from June through September 2012 (8 calves/replication).
      Animals were allowed a choice between tall fescue and sainfoin (SAN) or tall
      fescue and alfalfa (ALF) growing in strips (fescue, legume, and fescue-legume
      mixture). Incidence of use (scan samples) of legumes increased from the beginning
      to the end of the trials (P < 0.05), suggesting that cattle learned to mix
      legumes with tall fescue. Scan samples and assessments of pasture biomass removal
      revealed greater use of sainfoin than alfalfa when both legumes were abundant in
      the spring (P < 0.05); that pattern reversed toward the end of the growing season
      (P < 0.05) as the abundance of sainfoin declined more than that of alfalfa.
      Intake of forage per kilogram of gain was greater for SAN than for ALF in 2010 (P
      = 0.0003) and showed a tendency to be greater for SAN than ALF in 2012 (P =
      0.19). There were no differences in ADG between SAN and ALF in either year (1
      kg/d; P > 0.05). No incidences of bloat were detected. When cattle (3
      calves/treatment in 2010 and 8 calves/treatment in 2012) were slaughtered in
      September to assess meat quality and consumer acceptance, carcasses were lean (4%
      to 6% fat content of the longissimus muscle), but compared with ALF, SAN had
      higher marbling scores, quality grades (Select versus Standard), and back fat
      thicknesses (P < 0.05) in 2012. Steaks from cattle finished on SAN were redder in
      color than steaks from cattle finished on ALF (P < 0.05; 2012). Meat samples from
      SAN and ALF showed some differences in unsaturated fatty acid profiles and
      volatiles concentrations (P < 0.05), but consumer acceptance did not differ
      between SAN and ALF (P > 0.05). Thus, cattle incorporated a lower-quality grass
      into their diets even when legumes were available ad libitum during most grazing
      trials. Choices between tall fescue and legumes differing in the type of
      secondary compound (tannins vs. saponins) and bloating potential influenced
      patterns of forage use by cattle and led to differences in meat quality. 

PMID- 24671585
TI  - Variation in nutrient digestibility and energy intake are key contributors to
      differences in postweaning growth performance.
AB  - Pig weight variation represents an important source of lost production and
      profitability in the swine industry. To date, few experiments have classified how
      pigs of the same age but different weight utilize dietary energy and nutrients.
      The objective of this experiment was to characterize how pigs with varying
      weaning weights (WW) and postweaning growth performance differ in apparent total
      tract digestibility (ATTD) of energy or nutrient digestibility or energy
      utilization. Ninety-six barrows weaned at 18 to 22 d of age were selected from
      960 to represent the 10% of the lightest (LWW), median (MWW), and heaviest (HWW)
      at weaning (n = 32 pigs per WW category). Pigs were housed in metabolism crates
      for a 5-d acclimation period and a 27-d study and fed ad libitum quantities of a
      common diet containing titanium dioxide as an indigestible marker. Fecal grab
      samples and total urine were collected during a 3-d collection period at the
      beginning and end of the experiment. After the experiment, pigs within each WW
      category were further classified into the 33% slowest, median, or fastest ADG
      categories. This resulted in a total of 9 treatments in a nested design. Data
      were analyzed using the GLIMMIX procedure of SAS. There were no differences in
      ATTD according to WW at the beginning or end of the experiment, or when ADG was
      nested within WW at the beginning of the experiment. However, the ATTD of DM, GE,
      N, and ash, as well as the related DE, ME, and NE content, were greatest (P <
      0.01) in the median ADG categories of pigs at the end of the experiment. Energy
      intake increased with increasing WW (P < 0.001; NE intake = 1.40, 1.64, and 1.89
      Mcal/d for pigs from the LWW, MWW, and HWW, respectively). However, the ratio of
      calculated to actual ME intake was lower in LWW pigs than HWW pigs (P = 0.04;
      1.03 and 1.10 for LWW and HWW pigs, respectively). When ADG was nested within WW
      category, both increasing WW and ADG increased (P < 0.001) energy intake,
      utilization, and efficiency for gain, energy retained as tissue, and retained GE.
      The calculated to actual ME intake ratio differed (P < 0.03), supposedly because
      of differences in thermoneutrality, and therefore maintenance requirements.
      Reduced postweaning ADG appears to be driven by a combination of poor nutrient
      digestibility, energy intake, and, possibly, cold stress, which may provide
      avenues for more directed pig management strategies in the future to minimize
      variation within a group. 

PMID- 24671586
TI  - Adaptation to various sources of dietary sulfur by ruminants.
AB  - The objective of these experiments was to determine adaptation by ruminants to
      dietary sulfur. In Exp. 1, lambs (n = 54; BW = 33.6 +/- 0.4 kg) were allotted to
      3 treatments: 1) 0% added dietary S (0%S), 2) 0.2% added dietary S (0.2%S), or 3)
      0.4% added dietary S (0.4%S). Sulfur was added to the diet as Na(2)SO(4). Lambs
      fed the 0.2%S and 0.4%S diets had greater (P < 0.01) ADG and G:F compared to
      those fed the 0%S diet. There was time * diet interaction (P < 0.01) on ruminal
      hydrogen sulfide gas (H(2)S) concentrations. Ruminal H(2)S was not detected in
      lambs fed 0%S at any time. Ruminal H2S were not affected (P > 0.19) by diet on d
      1 or 8; however, H(2)S were greater (P < 0.01) for lambs fed 0.2%S and 0.4%S than
      for lambs fed 0%S on d 15, 22, and 29 (0.2% was 931, 846, and 1,131 mg/L and 0.4%
      was 975, 737, and 1,495 mg/L on d 15, 22, and 29, respectively). These data
      suggest it takes at least 29 d for peak ruminal H(2)S to occur after exposure to
      Na(2)SO(4). In Exp. 2, lambs (n = 66; BW = 51.1 +/- 0.4 kg) were allotted to 3
      treatments: 1) 60% dried distillers grains with solubles (DDGS), 2) corn-based
      diet with Na(2)SO(4), or 3) corn-based diet with H(2)SO(4). All diets were
      formulated to contain 0.4%S. Lambs fed Na(2)SO(4) had greater (P < 0.05) ADG,
      DMI, and G:F than those fed H(2)SO(4) or 60% DDGS. A time * diet interaction
      occurred (P < 0.01) for ruminal H(2)S. There was no difference (P = 0.82) in
      H(2)S of lambs on d 1. However, at d 14 and 27 lambs fed supplemental Na(2)SO(4)
      had the lowest H(2)S concentrations while lambs fed 60% DDGS had the greatest (P
      < 0.01 on both d); lambs fed H(2)SO(4) were intermediate and different than both.
      These data suggest that at the same dietary S concentration, acidic S sources
      increased H(2)S and decreased DMI and ADG. In Exp. 3, Angus cross calves (n = 72;
      average initial BW = 324 +/- 3 kg) were allotted to 3 treatments: 1) corn-based
      control d 0 through 85 (0%DDGS), 2) gradual step up to 60% DDGS diet (20% DDGS d
      0 to 6, 40% DDGS d 7 to 13, 50% DDGS d 14 to 20, and 60% DDGS d 21 to 85; Step
      up), or 3) 60% DDGS d 0 to 85 (60%DDGS). Overall, cattle fed 0%DDGS had increased
      (P < 0.05) DMI and ADG compared with those fed 60%DDGS or Step-up, and G:F was
      not affected (P = 0.42) by dietary treatment. On d 14, ruminal H(2)S
      concentrations were greater (P < 0.01) for cattle fed 60%DDGS and Step-up than
      for those fed 0%DDGS, and they did not differ (P >= 0.22) between DDGS-containing
      diets. These data illustrate that source of S impacts ruminal S metabolism and
      that S from DDGS is more readily reduced than S from Na(2)SO(4) or H(2)SO(4).

PMID- 24671587
TI  - Growth performance and carcass traits in pigs selected for indirect genetic
      effects on growth rate in two environments.
AB  - Production traits such as growth rate may depend on the social interactions
      between group members. These social interactions may be partly heritable and are
      referred to as indirect genetic effects (IGE) or social, associative, or
      competitive genetic effects. Indirect genetic effects may contribute to heritable
      variation in traits and can therefore be used to increase the response to
      selection. This, however, has hardly been tested by selection experiments. Our
      objective was to determine the effects of 1 generation of selection on IGE for
      growth (IGEg) in pigs on ADG, BW, ADFI, feed efficiency, and postmortem
      measurements. Sires (n = 24) and dams (n = 64) were selected to create a high vs.
      low contrast for IGEg in the offspring (n = 480). The IGE difference was 2.8 g
      ADG per pen mate, corresponding to 14 g higher ADG in high IGEg offspring
      compared to low IGEg offspring when housed in groups of 6 (i.e., (6 - 1) * 2.8 =
      14). Male (barrows) and female (gilts) offspring were housed in groups of 6 of
      the same IGEg classification, in either barren concrete pens or pens enriched
      with straw and wood shavings (n = 80 pens). Pigs were followed from birth to
      slaughter. Data were analyzed in a mixed model with pen as random factor. There
      was no difference in ADG between high and low IGEg pigs during the finishing
      period (wk 10 to 23). Opposite to expectations, high IGEg tended to have a 17 g
      lower ADG from weaning to slaughter (P = 0.08), which was caused by a higher BW
      of low IGEg pigs in wk 5 (P = 0.008). This led to a 2.3 kg lower carcass weight
      (P = 0.02) and 2.2 mm less muscle depth for high IGEg pigs (P = 0.03). High IGEg
      pigs had a higher stomach wall damage score (P = 0.01). Pigs on straw had a 25 g
      lower ADG during finishing (P = 0.03) and less stomach wall damage (P < 0.001).
      Fewer interventions against harmful behavior were required in high IGEg pigs. The
      unexpected results regarding IGEg may be due to several reasons. Despite initial
      power calculations showing good power, the IGEg contrast between groups may have
      been too small. Moreover, measures that were taken to limit harmful behavior may
      have had a substantial role. Harmful behavior such as tail biting may affect ADG
      and might underlie the effects of selection on IGEg in pigs. Research under
      commercial circumstances, where harmful behavior is likely to be more profound,
      may give more accurate insight into the benefits of selecting for IGEg. 

PMID- 24671588
TI  - Effects of calcium salts of soybean oil on factors that influence pregnancy
      establishment in Bos indicus beef cows.
AB  - The objective of this experiment was to compare fatty acid (FA) concentrations in
      plasma and reproductive tissues as well as hormones and expression of genes
      associated with pregnancy establishment in beef cows supplemented or not with Ca
      salts of soybean oil (CSSO) beginning after timed AI. Ninety nonlactating
      multiparous Nelore (Bos indicus) cows were timed inseminated on d 0 of the
      experiment and divided into 18 groups of 5 cows/group. Groups were randomly
      assigned to receive (as-fed basis) 100 g of a protein-mineral mix plus 100 g of
      ground corn per cow daily in addition to 1) 100 g/cow daily of CSSO (n = 9) or 2)
      100 g/cow daily of kaolin (CON; rumen-inert indigestible substance; n = 9). All
      groups were maintained in a single Brachiaria brizanta pasture (24 ha) with ad
      libitum access to forage and water. However, groups were segregated daily and
      offered treatments individually at the working facility during the experimental
      period (d 0 to 18). Blood samples were collected and transrectal ultrasonography
      was performed to verify ovulation and estimate corpus luteum (CL) volume
      immediately before AI (d 0) and on d 7 and 18 of the experiment. On d 19, 36 cows
      (18 cows/treatment; 2 cows/group) diagnosed without the presence of a CL on d 0
      but with a CL greater than 0.38 cm(3) in volume on d 7 and 18 were slaughtered
      for collection of conceptus, uterine luminal flushing, and tissue samples from
      the CL and endometrium. Cows receiving CSSO had greater concentrations of
      linoleic and other omega-6 FA in plasma (P < 0.01), endometrium (P <= 0.05), CL
      (P <= 0.05), and conceptus (P <= 0.08) compared to CON. On d 7 of the experiment,
      CSSO-supplemented cows had greater plasma progesterone concentrations (P < 0.01)
      and CL volume (P = 0.02) compared to CON, whereas no treatment effects were
      detected (P >= 0.15) for these parameters on d 18 (treatment * day interaction; P
      < 0.01). Cows receiving CSSO tended (P = 0.09) to have greater concentrations of
      interferon-tau in the uterine flushing media compared with CON. However, no
      treatment effects were detected for mRNA expression genes associated with
      pregnancy establishment in endometrial, CL, and conceptus samples (P >= 0.12). In
      summary, supplementing beef cows with 100 g of CSSO beginning after AI favored
      incorporation of omega-6 FA into their circulation, reproductive tissues, and
      conceptus, without impacting expression of genes associated with pregnancy
      establishment on d 19 of gestation. 

PMID- 24671589
TI  - Green leaf allowance and dairy ewe performance grazing on tropical pasture.
AB  - The objective of this study was to explain the influence of green leaf allowance
      levels on the performance of dairy ewes grazing a tropical grass. Seventy-two
      lactating ewes grazed Aruana guineagrass (Panicum maximum Jacq. cv. Aruana) for
      80 d. The treatments were 4 daily levels of green leaf allowance (GLA) on a DM
      basis corresponding to 4, 7, 10, and 13 kg DM/100 kg BW, which were named low,
      medium-low, medium-high, and high level, respectively. The experimental design
      was completely randomized with 3 replications. During the experimental period, 4
      grazing cycles were evaluated in a rotational stocking grazing method (4 d of
      grazing and 16 d of rest). There was a linear effect of GLA on forage mass, and
      increasing GLA resulted in increased total leaf mass, reaching an asymptotic
      plateau around the medium-high GLA level. The stem mass increased with increased
      GLA, and a pronounced increase was observed between medium-high and high GLAs.
      Increasing GLA increased both forage disappearance rate and postgrazing forage
      mass. Leaf proportion increased with GLA, peaking at the medium-high level, and
      the opposite occurred for stem proportions, which reduced until medium-high GLA
      level, followed by an increase on high GLA. Forage CP decreased linearly with
      GLA, and increasing GLA from low to high reduced CP content by 31%. On the other
      hand, NDF increased 14% and ADF increased 26%, both linearly in response to
      greater GLA levels. Total digestible nutrients decreased linearly by 8% when GLA
      increased from low to high level. Milk yield increased, peaking at medium-high
      GLA (1.75 kg ewe(-1) d(-1)) and decreased at high GLA level (1.40 kg ewe(-1) d(
      1)). Milk composition was not affected by the GLA levels. There was a reduction
      in stocking rate from 72 to 43 ewes/ha when GLA increased from low to high level.
      Productivity (milk yield kg ha(-1) d(-1)) increased as GLA increased, peaking at
      medium-low level (115 kg ha(-1) d(-1)). Although this tropical grass showed the
      same pattern in responses to GLA levels as reported in the literature with
      temperate pastures, the magnitude of the process changed and the maximum response
      in milk yield from lactating dairy ewes grazing a tropical pasture would be
      achieved with higher forage allowances than in temperate pastures. Overall,
      Aruana guineagrass grazed by lactating dairy ewes should be managed to provide 7
      to 10 GLA in kg DM/100 kg BW according to the production goals. 

PMID- 24671590
TI  - Inverted teats (Mammillae invertitae) in gilts - effect on piglet survival and
      growth rate.
AB  - In the modern pig industry, the increasing number of piglets born per litter
      augments the importance of the number of functional teats in the sow. The aim of
      this study was to evaluate the function and importance of inverted teats during
      nursing and to analyze structural and functional differences between the mammary
      glands of inverted teats versus normal teats. Nine farrowing gilts (8 purebred
      Swedish Yorkshire gilts and 1 cross between Swedish Yorkshire and Norwegian
      Landrace) and 94 piglets (59 piglets suckling normal teats, 32 piglets suckling
      protruded teats [i.e., previously inverted], 2 piglets suckling inverted teats,
      and 3 piglets suckling considerably smaller teats) were included in the study.
      Teat fidelity (keeping the same teat between the nursings) was registered,
      excluding the first 48 h postpartum. Piglet weight was recorded daily during the
      first week of life and thereafter once a week until weaning at 4 wk of age.
      Weight and growth rate were analyzed using repeated observation mixed-model
      analysis of variance. The 2 piglets that suckled the inverted teats were not able
      to emerge the teats and they were euthanized 4 and 8 d after birth, respectively,
      due to loss of BW. The average weight at weaning (28 d of age) was 8.1 kg (range
      3.2-13.8 kg). In the normal teats (n = 53), the weight of the corresponding
      mammary gland tissue at necropsy was positively correlated to the piglet average
      daily weight gain during wk 2 (r = 0.33, P < 0.05), 3 (r = 0.55, P < 0.001), and
      4 (r = 0.47, P < 0.001). In the protruded teats (n = 32), the weight of the
      corresponding mammary gland tissue was positively correlated to the piglet
      average daily weight gain during wk 2 (r = 0.63, P < 0.001) and 3 (r = 0.43, P <
      0.05). Among the piglets nursing normal teats, 82% kept fidelity to its teat and
      the corresponding percent for the protruded teats was 26%. In 7 of the 9 sows,
      the weaning weight of the piglets suckling protruded teats was numerically lower
      compared to the piglets suckling normal teats, although the difference was not
      statistically significant. Piglets nursing small teats had lower weaning weight
      (4.8 kg) and the corresponding mammary tissue also had lower weight (335 g). This
      study indicates the importance of an adequate number of well-developed and well
      functioning teats in healthy sows for the growth and development of the piglets
      but also emphasizes the complexity of the interaction between the nursing sow and
      her piglets. 

PMID- 24671591
TI  - Effect of dietary zinc and ractopamine hydrochloride on pork chop muscle fiber
      type distribution, tenderness, and color characteristics.
AB  - A total of 320 finishing pigs (PIC 327 * 1050; initially 98 kg) were used to
      determine the effects of adding Zn to diets containing ractopamine HCl (RAC) on
      muscle fiber type distribution, fresh chop color, and cooked meat
      characteristics. Dietary treatments were fed for approximately 35 d and consisted
      of a corn-soybean meal-based negative control (CON), a positive control diet with
      10 mg/kg of RAC (RAC+), and the RAC+ diet plus 75, 150, or 225 mg/kg added Zn
      from either ZnO or Availa-Zn. Loins randomly selected from each treatment (n =
      20) were evaluated using contrasts: CON vs. RAC+, interaction of Zn level *
      source, Zn level linear and quadratic polynomials, and Zn source. There were no
      Zn source effects or Zn source * level interactions throughout the study (P >
      0.10). Pigs fed RAC+ had increased (P < 0.02) percentage type IIX and a tendency
      for increased (P = 0.10) percent type IIB muscle fibers. Increasing added Zn
      decreased (linear, P = 0.01) percentage type IIA and tended to increase (P =
      0.09) IIX muscle fibers. On d 1, 2, 3, 4, and 5 of display, pork chops from pigs
      fed the RAC+ treatment had greater (P < 0.03) L* values compared to the CON. On d
      0 and 3 of display, increasing added Zn tended to decrease (quadratic, P = 0.10)
      L* values and decreased (quadratic, P < 0.03) L* values on d 1, 2, 4, and 5. Pigs
      fed RAC+ had decreased (P < 0.05) a* values on d 1 and 4 of display and tended to
      have decreased (P < 0.10) a* values on d 0 and 2 compared to CON pork chops. Pork
      chops from the RAC+ treatment had a tendency for increased (P < 0.08)
      oxymyoglobin percentage compared to CON pork chops on d 1, 2, 4, and 5. On d 0,
      as dietary Zn increased in RAC+ diets, there was a decrease (linear, P < 0.01) in
      the formation of pork chop surface oxymyoglobin percentage. Metmyoglobin reducing
      ability (MRA) of pork chops on d 5 was decreased in the RAC+ group. Chops from
      pigs fed added Zn had increased (quadratic, P < 0.03) MRA on d 3 and 5 of the
      display period. There was a trend for increased (linear, P = 0.07) cooking loss
      with increasing Zn in RAC diets and treatments did not affect tenderness as
      measured by Warner-Bratzler shear force (P > 0.07). In conclusion, RAC+ diets
      produced chops that were lighter and less red but maintained a greater percentage
      of surface oxymyoglobin throughout a 5-d simulated retail display. Ractopamine
      reduced MRA at the end of the display period, but supplementing Zn to RAC diets
      restored MRA to near CON treatment levels at the end of the display period. 

PMID- 24671592
TI  - Forage fiber effects on particle size reduction, ruminal stratification, and
      selective retention in heifers fed highly digestible grass/clover silages.
AB  - The objective of this study was to investigate the effect of NDF content in
      highly digestible grass/clover silage on particle size reduction, ruminal
      stratification, and selective retention in dairy heifers. The reduction in
      particle size from feed to feces was evaluated and related to feed intake,
      chewing activity, and apparent digestibility. Four grass/clover harvests
      (Mixtures of Lolium perenne, Trifolium pratense, and Trifolium repens) were
      performed from early May to late August at different maturities, at different
      regrowth stages, and with different clover proportions, resulting in silages with
      NDF contents of 312, 360, 371, and 446 g/kg DM, respectively, and decreasing NDF
      digestibility with greater NDF content. Four rumen-fistulated dairy heifers were
      fed silage at 90% of ad libitum level as the only feed source in a 4 * 4 Latin
      square design. Silage, ingested feed boluses, medial and ventral ruminal digesta,
      and feces samples were washed with neutral detergent in nylon bags of 10-MUm pore
      size, freeze dried, and divided into small (<0.212 mm), medium (0.212 to 1 mm),
      and large : LP; >1 mm) particles by dry-sieving. Chewing activity, rumen pool
      size, and apparent digestibility were measured. Intake of NDF increased linearly
      from 2.3 to 2.8 kg/d with greater NDF content of forages (P = 0.01), but silages
      were exposed to similar eating time (P = 0.55) and rumination time per kg NDF (P
      = 0.35). No linear effect of NDF content was found on proportion of LP in
      ingested feed boluses (P = 0.31), medial rumen digesta (P = 0.95), ventral rumen
      digesta (P = 0.84), and feces (P = 0.09). Greater proportions of DM (P < 0.001)
      and particulate DM (P = 0.008) were found in medial ruminal digesta compared with
      ventral rumen, and differences in DM proportion increased with greater NDF
      content (P = 0.02). Particle size distributions were similar for digesta from the
      medial and ventral rumen regardless of NDF content of the silages (P > 0.13). The
      LP proportion was >30% of particles in the ventral and medial rumen, whereas in
      the feces, the LP proportion was <2%. Particle size stratification of the rumen
      was undetectable regardless of NDF content of the silages, stressing that the
      retention mechanism of large undigested particles lies elsewhere than with
      particle entrapment in the rumen mat. In this study, forage particle breakdown,
      ruminal stratification, and retention of particles in the rumen were not affected
      by NDF content of highly digestible grass/clover silages. 

PMID- 24671593
TI  - Liver and skeletal muscle mitochondria proteomes are altered in pigs divergently
      selected for residual feed intake.
AB  - Animals selected for residual feed intake (RFI) can be used as a model to
      elucidate molecular explanations for differences in growth efficiency. The
      objective of this study was to determine the extent to which the protein profile
      and posttranslational modifications of mitochondria from skeletal muscle and
      liver relate to feed efficiency gains in pigs divergently selected for RFI.
      Mitochondria were isolated from the longissimus dorsi (LD) muscle and the liver
      from pigs (n = 9 each for the high and low RFI line; BW = 95.8 kg). Mitochondria
      protein profile differences were determined using two-dimensional difference in
      gel electrophoresis. Proteins were identified using electrospray ionization mass
      spectrometry. In the line comparison, the beta subunit of ATP synthase, heat
      shock protein (HSP) 60, and HSP70, were identified as being increased in
      mitochondria from the liver of the low RFI line (23 to 50%; P < 0.1). These
      differences were not observed in the other comparisons. In the LD, proteins
      identified as being different between RFI phenotypes included HSP70 and subunit 1
      of the cytochrome bc1 complex. These data indicate that genetic selection for RFI
      tends to result in a consistent change in mitochondrial protein profile. In
      contrast, classification by phenotype demonstrates that phenotypic differences in
      RFI are not specifically associated with alterations of the mitochondria protein
      profile. 

PMID- 24671594
TI  - Genetic characterization of a herd of the endangered Danish Jutland cattle.
AB  - In this paper we present results from a genetic characterization of a herd of the
      Danish Jutland cattle breed named the Kortegaard herd (n = 135; 57 males and 78
      females). The herd is genotyped on the Bovine HD BeadChip microarray with 697,548
      evenly spaced SNP across the bovine genome. The aim of the study was to
      characterize the genetic profile of the Kortegaard herd, which has been closed
      for several generations, by quantifying the degree of genetic homogeneity within
      the herd and to compare its genetic profile to that of other cattle breeds. A
      total of 868 animals from the Angus, Belgian Blue, Charolais, Friesian, Hereford,
      Holstein, Holstein-Friesian crosses, Limousin, and Simmental breeds was used for
      genetic profile comparisons. The level of genetic variation within the breeds
      were quantified by the expected heterozygosity (H(E)), observed heterozygosity
      (H(O)), average minor allele frequency (MAF), the degree of polymorphism, and
      runs of homozygosity (ROH), which are contiguous lengths of homozygous genotypes
      of varying length. Interestingly, the Kortegaard herd had the lowest within-breed
      genetic variation (lowest H(E), H(O), and MAF), showed moderate levels of short
      ROH (<5 Mb), and had the highest mean long ROH (>5 Mb) compared to all the other
      breeds. This is possibly due to recent consanguineous matings, a strong founder
      effect, and a lack of gene flow from other herds and breeds. We further examined
      whether the observed genetic patterns in the Kortegaard herd can be used to
      design breeding strategies for the preservation of the genetic pool by focusing
      on a subset of SNP outside homozygote regions. By calculating the pairwise
      identical-by-state between all possible matings, we designed a breeding plan that
      maximized heterozygosity in the short term. The benefits and limitations of such
      a breeding strategy are discussed.

PMID- 24671595
TI  - Polymorphism in 3' untranslated region of the pig PPARA gene influences its
      transcript level and is associated with adipose tissue accumulation.
AB  - The PPARA (peroxisome proliferator-activated receptor-alpha) gene encodes a
      nuclear receptor that plays an important role in fatty acid catabolism by
      transcriptional regulation of genes involved in fatty acid oxidation and can be
      considered as a candidate gene for fatness traits in the pig. The aim of the
      study was to search for a functional polymorphism in 3' untranslated region
      (UTR), their association with production traits, and postnatal PPARA transcript
      level in 2 skeletal muscles (longissimus and semimembranosus) of 5 commercial pig
      breeds (Polish Landrace [PL], Polish Large White [PLW], Duroc, Pietrain, and
      Pulawska). Altogether, 9 novel polymorphisms (8 SNP and 1 indel) were found in
      the 3' UTR. The in silico analysis revealed 6 putative microRNA target sequences
      in the analyzed region. The c.*636A>G substitution was widely distributed across
      breeds and located near the putative target sequence for miR-224. The relative
      PPARA transcript level was higher (P < 0.05) in LM of AA than in those of GG
      homozygous animals for SNP c.*636A>G. The luciferase assay revealed that miR-224
      probably acts as a negative regulator of the PPARA expression in pig adipocytes
      (P = 2.9 * 10(-7)), but we did not observe the effect of the A or G alleles on
      the interaction between miR-224 and its putative target sequence. We hypothesize
      that the 2 predominant haplotypes, differing at 4 sites (including c.*636A>G),
      present different architecture of its 3' UTR and it could affect the level of the
      transcript. The c.*636A>G SNP, analyzed in PL and PLW, was significantly
      associated with backfat thickness at 3 points (P < 0.05) and intramuscular fat
      content (P < 0.01) in PL. Suggestive associations were found between 4 SNP
      (c.*321A>C, c.*324G>C, c.*626T>C, and c.*636A>G) and fatty acid contents in LM
      and subcutaneous and visceral fat tissue of PL, PLW, Duroc and Pietrain pigs. The
      PPARA mRNA level was higher in semimembranosus muscle than in LM (P = 8.38 * 10(
      12)) in a general comparison and the same trend was found in most breeds (except
      for PL) and at all tested days of age (60, 90, 120, 150, 180, and 210 d). The
      effect of breed was highly significant in a general comparison (P = 0.48 * 10(
      8)), but there was no common expression pattern in both muscles among different
      age groups. We conclude that the c.*636A>G SNP in the PPARA gene can be
      considered in PL breed as a useful genetic marker for adipose tissue
      accumulation. 

PMID- 24671598
TI  - Effect of dietary trace mineral supplementation and a multi-element trace mineral
      injection on shipping response and growth performance of beef cattle.
AB  - To examine the effect of trace mineral (TM) status and TM injection on growth
      performance and carcass characteristics in beef cattle, 40 steers were used in a
      growing and finishing study. Steers were stratified by weight (323 +/- 14.8 kg)
      and assigned to 1 of 2 treatments for an 84-d depletion period: 1) a corn silage
      based diet supplemented with Cu, Mn, Se, and Zn to meet or exceed NRC
      recommendations (CON), or 2) CON diet without supplemental Cu, Mn, Se, or Zn but
      supplemented with 300 mg Fe and 5 mg Mo/kg diet DM as dietary TM antagonists
      (DEF) to induce mild deficiencies. To mimic shipping stress, steers were shipped
      for 20 h on d 88 and were received back on d 89. On d 91 an equal number of
      steers from both dietary treatments were injected with sterilized saline (SAL) or
      Multimin 90 (MM; containing 15, 60, 10, and 5 mg/mL of Cu, Zn, Mn, and Se,
      respectively) at a dose of 1 mL/68 kg BW. Steers were fed a common finishing diet
      supplemented with 10 mg Cu, 20 mg Mn, 0.1 mg Se, and 30 mg Zn/kg diet DM for the
      90-d repletion period. Steers were harvested 91 d postinjection and carcass data
      were collected. During the depletion period, diet did not affect BW, ADG, DMI, or
      G:F (P > 0.20). During the shipping period (defined as the time between 2-d
      consecutive weights on d 83 and 84 and d 90 and 91), DEF steers tended to lose
      more weight per day than CON steers (P = 0.06) and had lesser DMI (P = 0.03),
      suggesting that response to shipping stress may be modulated by TM status. During
      the repletion period, ADG of DEF + MM steers was greater (P = 0.03) compared with
      DEF + SAL and was not different (P = 0.92) among CON + MM and CON + SAL steers.
      There was no effect of diet or injection on HCW or dressing percentage (P >
      0.20). Within the CON group, TM injection decreased yield grade (P = 0.03) but
      did not affect yield grade of DEF steers (P > 0.20). Steers given TM injection
      had a larger rib eye area (P = 0.04) regardless of previous diet. Interestingly,
      both diet and injection affected marbling scores (MS), where CON steers had
      greater MS than DEF steers (P = 0.01) and MM steers had greater MS than SAL
      steers (P = 0.04). These results indicate that adequate TM nutrition is essential
      for marbling development, during both the growing and finishing phases. Overall,
      an injectable mineral improved rib eye area and MS regardless of initial TM
      status and improved growth of mildly TM deficient steers. 

PMID- 24671599
TI  - Technical note: physiological response of beef heifers after receiving a reused
      controlled internal drug release insert processed with different heat-treating
      methods.
AB  - Eighty-one prepubertal beef heifers were used to evaluate effects of used
      controlled internal drug release (CIDR) insert heating methods on concentrations
      of progesterone after CIDR insert reinsertion. Heifers were stratified by weight
      and birth date and then assigned to receive a new CIDR insert (New; n = 10) or 1
      of 8 used (7 d prior use) CIDR insert treatments: 1) no processing (Used; n =
      10), 2) autoclaved (Autoclaved; n = 8), 3) processed in dishwasher (Dishwasher; n
      = 8), 4) processed in microwave for 30 s (Microwave; n = 10), 5) processed in
      toaster oven (Oven; n = 9), 6) processed in clothes dryer (Dryer; n = 10), 7)
      processed in boiling water (Boiled; n = 8), or 8) stored outdoors for 60 d
      (Outside; n = 8). Used CIDR inserts were processed at 121 degrees C for 30 min
      for autoclaved and oven treatments, at 121 degrees C for boiled treatment, and
      for 30 min for dryer and dishwasher treatments. Blood samples were collected on d
      -10, immediately before CIDR insert insertion (d 0), 3 h after CIDR insert
      insertion (3 h), daily while CIDR insert was in place (d 1 to 11), and 24 h after
      CIDR insert removal (d 12) for analysis of concentrations of progesterone.
      Subjective color scores (1 = bright white to 5 = completely stained yellow/red)
      were assigned to each CIDR insert after d 11. A treatment * time interaction (P <
      0.0001) was present for concentrations of progesterone. Concentrations of
      progesterone were similar (P > 0.10) for heifers receiving a used CIDR insert
      compared with heifers receiving CIDR inserts processed in a dishwasher,
      microwave, oven, dryer, or boiling water (collectively reported as "Processed").
      However, heifers receiving autoclaved CIDR inserts had greater (P < 0.05)
      concentrations of progesterone from h 3 to d 3 but similar (P > 0.10)
      concentrations of progesterone from d 4 to d 11 compared with heifers receiving
      used or processed CIDR inserts. From d 1 to 11 heifers receiving outside CIDR
      inserts had decreased (P < 0.05) concentrations of progesterone compared with all
      other treatments. Heifers receiving autoclaved CIDR inserts had greater (P <
      0.05) concentrations of progesterone compared with all other treatments at 3 h
      and 1 d, whereas heifers receiving new CIDR inserts had greater (P < 0.05)
      concentrations of progesterone from d 6 to 11 compared with all other treatments.
      Outside CIDR inserts were more discolored (P < 0.001) compared with all other
      treatments. Processing used CIDR inserts with a dishwasher, microwave, oven,
      clothes dryer, boiling water, or full environmental exposure did not result in a
      pattern of concentrations of progesterone similar to that of autoclaved or new
      CIDR inserts. 

PMID- 24671600
TI  - BIOETHICS SYMPOSIUM II: current factors influencing perceptions of animals and
      their welfare.
AB  - To address escalating concerns about livestock animal care and welfare it is
      necessary to better understand the factors that may predispose people to develop
      such concerns. It has been hypothesized that experiences with, beliefs about, and
      emotional connections to animals may influence level of perceived obligation
      toward and therefore concern for animals. However, the extent to which people's
      classifications of animals and their status as pet owners may impact their views
      on food animal care and welfare practices remains unclear. An online survey of
      798 U.S. households was therefore conducted in June 2012 to understand
      differences in consumer sentiment towards various animal species, classification
      of certain species (as pet, livestock or neither), and variations in food animal
      welfare concerns between dog and/or cat owners and those who do not own such
      species. Sixty-six percent of households in the survey owned at least 1 animal.
      Forty-eight percent owned dogs, 41% owned cats, 3% owned horses, and 10% owned
      other animals. As expected, dogs and cats were classified by most respondents
      (90%) as pets. Most respondents similarly categorized rabbits (58%) and horses
      (55%) as pets, although consensus was not found for horses with 27% classifying
      them as livestock animals and 18% as neither pets nor livestock. Over 80% of
      respondents classified beef cows, dairy cows, pigs, chickens, and turkeys as
      livestock. The majority of survey respondents were opposed to eating cats and
      dogs followed closely by horses due to ethical and/or spiritual reasons. Dog
      and/or cat owners more often reported having a source for animal welfare
      information (68%) than those who did not own these species (49%). Additionally,
      dog and/or cat owners were more concerned about food animal welfare for both
      domestically raised food animals and those raised outside the United States (dog
      and/or cat owners mean level of concern was 3.88 for domestic animal welfare and
      5.16 for those raised outside the United States compared with non-dog or -cat
      owners with means of 4.46 and 5.46, respectively). Although a causal relationship
      cannot be established, pet ownership and increased concern for food animal
      welfare appear to be correlated. These data suggest that increased interest in
      protecting food animals may stem from interactions with and emotional connections
      to pets, especially when combined with other factors such as having a source for
      animal welfare information, education level, age, and gender. 

PMID- 24671601
TI  - Freezing and thawing or freezing, thawing, and aging effects on beef tenderness.
AB  - The objective of this study was to determine the effect of freezing and thawing
      or freezing and thawing with an additional aging period after frozen storage on
      the tenderness of longissimus lumborum (LL) and semitendinosus (ST) steaks
      relative to aged, fresh steaks. Left-side LL and ST (n = 35 each) were obtained
      from U.S. Select carcasses classified at the grading stand by the U.S. Meat
      Animal Research Center visible and near-infrared spectroscopy tenderness system
      to have predicted slice shear force greater than 16.5 kg at 14 d postmortem. At 2
      d postmortem, 2.54 cm thick steaks were cut from each muscle and assigned to 1 of
      the following treatments: 2 d fresh (2FRESH), 2 d freeze + thaw (2FREEZE), 2 d
      freeze + thaw + 12 d age (2FREEZE+12AGE), 14 d fresh (14FRESH), 14 d freeze +
      thaw (14FREEZE), 14 d freeze + thaw + 14 d age (14FREEZE+14AGE), and 28 d fresh
      (28FRESH). Steaks assigned to a freezing treatment were frozen at -26 degrees C
      for 30 d before thawing/cooking or thawing with an additional aging period at 2
      degrees C. Slice shear force for LL and ST was lower (P < 0.01) for 2FREEZE (27.4
      and 24.5 kg) and 14FREEZE (22.4 and 22.4 kg) compared to 2FRESH (33.0 and 29.2
      kg) and 14FRESH (25.3 and 25.5 kg), respectively. Slice shear force for LL and ST
      was lower (P < 0.01) for 2FREEZE+12AGE (17.8 and 20.8 kg) and 14FREEZE+14AGE
      (14.6 and 19.0 kg) compared to 14FRESH (25.3 and 25.5 kg) and 28FRESH (18.7 and
      21.7 kg), respectively. Desmin degradation for LL was not different (P > 0.05)
      between 2FREEZE (21.0%) and 2FRESH (14.6%) or between 14FREEZE (40.4%) and
      14FRESH (38.4%); however, desmin degradation was higher (P < 0.06) in
      2FREEZE+12AGE (46.7%) and 14FREEZE+14AGE (71.1%) when compared to 14FRESH (38.4%)
      and 28FRESH (60.5%), respectively. Cooking loss for LL was higher (P < 0.01) in
      2FREEZE+12AGE (15.2%) compared to 14FRESH (14.0%) but was not different (P >
      0.05) between 14FREEZE+14AGE (15.0%) and 28FRESH (14.3%). Freezing and thawing or
      a combination of freezing, thawing, and aging resulted in increased tenderness
      for LL and ST steaks when compared to fresh steaks with the same aging time.
      These results indicate freezing could be incorporated into normal commercial
      product distribution processes to improve the consistency of meat tenderness.
      Researchers who freeze steaks before tenderness assessment should be aware and
      acknowledge that freezing affects tenderness data. 

PMID- 24671602
TI  - Effects of three dehorning techniques on behavior and wound healing in feedlot
      cattle.
AB  - Crossbred horned steers and heifers (n = 40; BW = 311.8 +/- 4.7 kg) were used to
      determine the effect of dehorning methods on pain, cattle behavior, and wound
      healing. Cattle were blocked by weight and randomly assigned to 1 of 4
      treatments: 1) control (CON), 2) banded using high tension elastic rubber (BAND),
      3) mechanically removed (MECH), or 4) tipped (TIP). Vocalization and behavior
      were recorded during the dehorning process. Wound healing scores, attitude, gait
      and posture, appetite, and lying were recorded daily. Vocalization scores were
      highest for MECH cattle and BAND cattle vocalized more than TIP and CON (P <
      0.05). Attitude (P = 0.06), gait and posture (P = 0.06), and lying scores (P <
      0.05) were higher for BAND cattle in the days following procedures compared to
      MECH, TIP, and CON cattle. Cattle in the BAND treatment tended (P < 0.13) to have
      higher appetite scores than the other methods. Wound healing scores (horn bud and
      bleeding) were higher for BAND cattle than MECH, TIP, and CON cattle (P < 0.05).
      These data indicate that MECH is a painful procedure for cattle at the time of
      the procedure. Banding to remove horns from cattle is not recommended based on
      the data and observations from this study. 

PMID- 24671603
TI  - Frailty prevalence and 10-year survival in community-dwelling older adults:
      results from the ESTHER cohort study.
AB  - The frailty index (FI), defined by a deficit accumulation approach, has emerged
      as a promising concept in gerontological research, but applications have been
      mostly restricted to populations from Canada and the United States aged 65 years
      or older. Baseline data from the German ESTHER cohort study (N 9,886; age 50-75;
      mean follow-up 8.7 years) were used to create a FI through a deficit accumulation
      approach. For estimation of frailty prevalence, we used cut-points for the FI to
      define three categories (non-frail 0 to <=0.20; pre-frail >0.20 to <0.45; frail
      >=0.45). We assessed variation of the FI by age and sex: 10-year survival
      according to baseline FI was assessed by Kaplan-Meier curves and bivariate and
      multivariate Cox proportional hazard models. Cubic splines were used to assess
      sex-specific dose-response associations. Prevalence of frailty was 9.2 and 10.5%
      in women and men, respectively. Age-specific prevalence of frailty ranged from
      4.6% in 50-54 year old participants to 17.0% in 70-75 year old participants.
      Below 60 years of age, men had a higher FI than women. However, the FI showed a
      stronger increase with age among women (3.1% per year) than among men (1.7% per
      year) and was higher among women than men in older age groups. Adjusted hazard
      ratios (95% confidence intervals) for all-cause mortality were 1.08 (0.84-1.39),
      1.32 (1.05-1.66), 1.77 (1.41-2.22), and 2.60 (2.11-3.20) for the 2nd, 3rd, 4th,
      and 5th quintile of the FI compared to 1st quintile, respectively. There was a
      strong dose-response relationship between the FI and total mortality among both
      men and women and both younger (<65 years) and older subjects. We found sex
      differences in the FI and its increase with age, along with a consistent strong
      association of the FI with mortality in both sexes, even for age group 50-64.

PMID- 24671604
TI  - Computational investigation of charge injection and transport properties of a
      series of thiophene-pyrrole based oligo-azomethines.
AB  - The present study explores the structural, charge carrier injection and transport
      properties of a series of thiophene-pyrrole based oligo-azomethines using density
      functional theory (DFT) methods. Our findings show that the presence of a bulky
      substituent adversely affects these properties. However, the electronic effect of
      substituents may be utilized to tune these properties by substitutions at
      suitable positions. Values of frontier orbitals, ionization energies, and
      electron affinities are calculated for each compound to predict the ease of
      charge injection from metal electrodes to these azomethines and the stabilities
      of their ionic forms. In addition to having large injection barriers, lack of
      stability of the anions may hinder the electron injection. However, most of the
      compounds have excellent hole injection capability. Computation of reorganization
      energies and electronic couplings followed by charge transfer rates and
      mobilities show large carrier mobilities for some of the studied compounds.
      Considering both the injection capability and carrier mobilities, it is found
      that a thiophene-pyrrole azomethine without any substituent and substituted
      azomethines with a methyl, methoxy or amine group at the 3 position of the
      pyrrole ring may act as efficient materials for the hole transport layer. 

PMID- 24671606
TI  - Does the VerifyNow P2Y12 assay overestimate "therapeutic response" to
      clopidogrel? Insights using short thrombelastography.
AB  - In contrast to short thrombelastography (s-TEG) which utilises adenosine
      diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses
      prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based
      upon previous observations, we hypothesised that VN-P2Y12 overestimates the
      therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12
      was performed in 43 healthy volunteers and 170 patients either on or off
      clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the
      effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP
      alone. A higher proportion of individuals had a result indicating high platelet
      reactivity (HPR) with s-TEG than VN-P2Y12 in (i) 43 clopidogrel naive volunteers
      (95.3% vs 81.4%, p = NS); (ii) 28 volunteers loaded with clopidogrel 600 mg
      (39.3% vs 10.7 %, p = < 0.01); (iii) 123 clopidogrel naive patients (93.5% vs
      78%, p = < 0.0001); (iv) 47 patients on clopidogrel 75 mg (42.6% vs 4.3%, p = <
      0.0001). In 59 patients loaded with clopidogrel 600 mg/900 mg, a greater
      proportion had a "therapeutic response" with VN-P2Y12 compared to s-TEG,
      regardless of the threshold for defining HPR with VN-PY12 (P2Y12 reaction units
      >= 230 or 208). Furthermore, adding PGE1 to ADP in s-TEG potentiated the anti
      aggregatory effects of clopidogrel compared with ADP alone. In conclusion, VN
      P2Y12 overestimates the functional effects of clopidogrel in some individuals,
      possibly because it utilises PGE1 in addition to ADP. This could have
      implications for the ability of VN-P2Y12 to stratify patients as "responders" or
      "non-responders" to clopidogrel. 

PMID- 24671605
TI  - Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice.
AB  - P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels
      activated by synaptically released extracellular adenosine 5'-triphosphate. The
      P2X4 subtype is abundantly expressed in the central nervous system and is
      sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses
      identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or
      preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and
      wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to
      ethanol intake. The early acquisition and early maintenance phases of ethanol
      intake were measured with three different drinking procedures. Further, we tested
      the effects of ivermectin (IVM), a drug previously shown to reduce ethanol's
      effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to
      differentially alter stable ethanol intake in KO and WT mice. Depending on the
      procedure and the concentration of the ethanol solution, ethanol intake was
      transiently increased in P2X4R KO versus WT mice during the acquisition of 24-h
      and limited access ethanol intake. IVM significantly reduced ethanol intake in
      P2X4R KO and WT mice, but the degree of reduction was 50 % less in the P2X4R KO
      mice. Western blot analysis identified significant changes in gamma-aminobutyric
      acidA receptor alpha1 subunit expression in brain regions associated with the
      regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence
      that P2X4Rs contribute to ethanol intake and indicate that there is a complex
      interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems.

PMID- 24671607
TI  - Stem cell therapy: a new approach to the treatment of refractory depression.
AB  - To better understand the relationship of repeated exposure to adversity during
      early development as a risk factor for refractory depression, we exposed pregnant
      female rats to ethanol and the resulting pups to corticosterone during
      adolescence. A stressful forced swim test was then used to induce depression-like
      behavior. The adolescent rat brains were examined for the possible therapeutic
      benefit of a combination of sertraline, an antidepressant, and neural stem cells
      (NSCs) complexed with atelocollagen in relation to the level of GABAergic
      interneuron and synaptic protein density in different brain regions. The combined
      exposures of prenatal and adolescent stress resulted in a reduction in
      parvalbumin (PV)-positive phenotype of GABAergic interneurons and reduced
      postsynaptic density protein 95 (PSD-95) levels in the anterior cingulate cortex,
      amygdala, and hippocampus. Treatments with sertraline and NSCs reversed the
      reductions in PV-positive cells and PSD-95 levels. Furthermore, the combined
      treatment of sertraline and NSCs resulted in reduced depressive-like behaviors.
      These experiments underscore a potentially important role for synaptic remodeling
      and GABAergic interneuron genesis in the treatment of refractory depression and
      highlight the therapeutic potential of stem cell and pharmacological combination
      treatments for refractory depression. 

PMID- 24671608
TI  - Do we know (or just believe) that partial nephrectomy leads to better survival
      than radical nephrectomy for renal cancer?
AB  - PURPOSE: Partial nephrectomy (PN) has become the gold standard for treating small
      renal masses amenable to such an approach. Surprisingly, the single randomized
      controlled trial of PN versus radical nephrectomy (RN) indicated an overall
      survival benefit for RN over PN. Recent studies have shed light on this
      discordance, and this review will attempt to discern what is known at present.
      RESULTS: Multiple retrospective observational studies have demonstrated superior
      outcomes with PN compared with RN. Whether the observed survival benefit with PN
      is the result of renal functional advantages or the result of selection bias and
      other unmeasured variables is up for discussion. A meta-analysis of 21 studies
      including the EORTC 30904 found a 19 % reduction in all-cause mortality (p =
      0.0001) and 29 % reduction in cancer-specific mortality (p = 0.0002) with PN
      versus RN. Recent analysis of SEER-Medicare data revealed that patients
      undergoing RN had similar survival when compared with non-cancer controls,
      further supporting concerns about selection biases in prior observational series.
      DISCUSSION: Although PN is clearly of benefit for those likely to experience end
      stage renal disease with RN, a survival benefit with PN in the elective setting
      is not proven at present. While experts may still believe PN to improve survival
      for these patients, the only level I evidence in the field would suggest
      otherwise, and selection bias is undoubtedly responsible for a significant part
      of the improved survival observed in retrospective studies. Given recent
      evidence, any further push to limit the role of RN should be tempered until we
      know PN is indeed superior.

PMID- 24671609
TI  - DNA comparison between operative and biopsy specimens to investigate stage pT0
      after radical prostatectomy.
AB  - PURPOSE: The aim was to eliminate, by DNA comparison, any identity mismatch
      between operative and biopsy specimens and to analyse the determinants of all pT0
      prostate cancers occurred in a single institution. METHODS: All prostate pT0
      cases in a single institution over 20 years were investigated. None of the
      patients had been diagnosed after a transurethral resection of the prostate nor
      had they received neoadjuvant hormonal treatment. The biopsies performed in other
      centres had been referred for a centralized pathologic re-analysis. DNA analysis
      was performed in samples from operative and biopsy specimens, and pairs of
      tissues were blindly constituted. Correct matching was verified in each pair and
      compared to the original database in order to comment on the occurrence of
      identity mismatches in the series. RESULTS: Nineteen patients (0.77 %) had been
      diagnosed as having pT0 prostate cancer among the 2,462 RP procedures performed
      over 19 years. The biopsy re-analysis invalidated the initial diagnosis of
      prostate cancer in one biopsy set performed elsewhere. Among 12 entirely
      processed cases, the biochemistry procedure evaluated as "very unlikely" the
      occurrence of an error in tissue identification in the biopsy setting, during the
      surgical procedure or the pathological analysis. No identification error of
      tissue samples was established in this first verified pT0 series. CONCLUSIONS:
      Although it must be suspected, specimen identification error was not a cause for
      pT0 prostate cancer. Only after a full pathological and DNA verification, the pT0
      stage remains a sole entity, unexplained in most cases.

PMID- 24671611
TI  - A network modeling approach for the spatial distribution and structure of bone
      mineral content.
AB  - This study aims to develop a spatial model of bone for quantitative assessments
      of bone mineral density and microarchitecture. A spatially structured network
      model for bone microarchitecture was systematically investigated. Bone mineral
      forming foci were distributed radially according to the cumulative normal
      distribution, and Voronoi tessellation was used to obtain edges representing bone
      mineral lattice. Methods to simulate X-ray images were developed. The network
      model recapitulated key features of real bone and contained spongy interior
      regions resembling trabecular bone that transitioned seamlessly to densely
      mineralized, compact cortical bone-like microarchitecture. Model-simulated
      imaging profiles were similar to patients' X-ray images. The morphometric metrics
      were concordant with microcomputed tomography results for real bone. Simulations
      comparing normal and diseased bone of 20-30 to 70-80 year-olds demonstrated the
      method's effectiveness for modeling osteoporosis. The novel spatial model may be
      useful for pharmacodynamic simulations of bone drugs and for modeling imaging
      data in clinical trials.

PMID- 24671610
TI  - Statin use is associated with decreased prostate cancer recurrence in men treated
      with brachytherapy.
AB  - PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that
      statin medications may have anticancer activity. We sought to determine whether
      statin use was associated with improved clinical outcome in men treated with
      brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with
      prostate cancer treated with permanent Iodine-125 brachytherapy between January
      1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e.,
      American Brachytherapy Society selection criteria) were used for selecting
      patients for brachytherapy. Biochemical failure was defined using the Phoenix
      definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated
      with brachytherapy, 174 patients (70 %) were identified as using statin
      medications, either during initial visit or during follow-up. Median PSA follow
      up was 51 months after date of implant (range 9.4-140.35). Overall biochemical
      failure rate was 7.3 % (18 patients). On univariate analysis, statin use was
      associated with significantly improved freedom from biochemical failure [hazard
      ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate
      Cox analysis performed with the variables statin use, pretreatment PSA, clinical
      T stage, Gleason score, and D90 or V100, statin use remained significantly
      associated with improved freedom from biochemical failure (HR 0.288; 95 % CI
      0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a
      significant improvement in freedom from biochemical failure in this cohort of men
      treated with brachytherapy for prostate cancer. Further investigation into the
      favorable effect of statin use on brachytherapy and radiation therapy in general
      is warranted, including prospective trials.

PMID- 24671612
TI  - Locoregional multiple nodular panniculitis induced by Pseudomonas aeruginosa
      without septicemia: three cases and focus on predisposing factors.
AB  - IMPORTANCE: Pseudomonas aeruginosa-induced locoregional multiple nodular
      panniculitis without septicemia is an underreported condition, with only 3 cases
      reported to date. We report 3 new cases of P aeruginosa-induced multiple nodular
      panniculitis without septicemia and describe common features among all 6 cases,
      thus providing the first description, to our knowledge, of the natural history
      and potential predisposing factors for this entity. OBSERVATIONS: Median age of
      the 6 patients was 74 years (range, 54-84 years). Patients had inflammatory
      nodules on a lower limb (n = 6) that were unilateral (n = 6) and had no fever (n
      = 5). Blood cultures were negative (n = 5). Skin biopsy specimens revealed
      panniculitis (n = 5), with skin cultures positive for P aeruginosa (n = 6). Skin
      nodules resolved with systemic antibiotics (n = 5). The comorbidities recorded
      were type 1 or 2 diabetes mellitus (n = 5), overweight (n = 3), and combined
      locoregional anatomical changes in the lower limbs (n = 5). Local skin injury,
      which constituted the portal entry, was present in all cases, especially leg
      ulcers (n = 3). CONCLUSIONS AND RELEVANCE: We describe P aeruginosa-induced
      locoregional nodular panniculitis as a distinct entity. This should be
      investigated in elderly, diabetic, overweight patients with inflammatory nodules
      on a lower limb associated with locoregional anatomical changes and skin injury,
      with the optimal antibiotic regimen introduced as rapidly as possible.

PMID- 24671613
TI  - Chemical markers of occupational exposure to teak wood dust.
AB  - A novel high-performance liquid chromatographic/ultraviolet method was developed
      to detect lapachol (LP) and deoxylapachol (DLP) in wood dust as chemical markers
      of teak wood (a suspected human carcinogen). The specificity of this analysis was
      determined by noting the absence of LP and DLP in 12 other specimens of different
      woods belonging to the angiosperm family. The consistency was examined by
      analyzing teak from three different sources, where the percentages (wt/wt) of the
      chemicals ranged from 0.006 to 0.261 for LP and from 0.038 to 0.497 for DLP,
      respectively. Although the LP and DLP components of teak varied according to
      source, a very high correlation coefficient (r (2) > 0.98 always) was found
      between the content of the two markers in the bulk specimens and in bulk dust
      derived from them. The method was then applied to teak dust collected on
      polyvinylchloride filters from aerosol in an exposure chamber in the range of
      mass loadings between 0.03 and 3.65 mg, which corresponds to a dust exposure
      between 0.124 and 8.703 mg m(-3) for a sampling time of 2h. A field test was also
      carried out in a small factory where teak was used. A good correlation was
      confirmed between LP and DLP versus the dust collected on the filter in both
      cases. LP and DLP can be markers to estimate the true quantities of teak dust
      inhaled in a workplace with mixed wood dust, provided the results are matched to
      the content of LP and DLP in the bulk wood. LP and DLP have also been proposed as
      the agents responsible for allergic reaction to teak dust. Therefore, it would be
      useful to evaluate the exposure to these two substances even without a
      relationship to teak dust exposure.

PMID- 24671615
TI  - Bovine calves as ideal bio-indicators for fluoridated drinking water and endemic
      osteo-dental fluorosis.
AB  - Relative susceptibility to fluoride (F) toxicosis in the form of osteo-dental
      fluorosis was observed in an observational survey of 2,747 mature and 887
      immature domestic animals of diverse species living in areas with naturally
      fluoridated (>1.5 ppm F) drinking water. These animals included buffaloes
      (Bubalus bubalis), cattle (Bos taurus), camels (Camelus dromedarius), donkeys
      (Equus asinus), horses (Equus caballus), goats (Capra hircus), and sheep (Ovis
      aries). Of these mature and immature animals, 899 (32.7 %) and 322 (36.3 %)
      showed evidence of dental fluorosis with varying grades, respectively. Their
      incisor teeth were stained with light to deep brownish color. On clinical
      examination, 31.2 % mature and 10.7 % immature animals revealed periosteal
      exostoses, intermittent lameness, and stiffness of tendons in the legs as signs
      of skeletal fluorosis. The maximum susceptibility to fluoride toxicosis was found
      in bovines (buffaloes and cattle) followed by equines (donkeys and horses),
      flocks (goats and sheep), and camelids (camels). The bovine calves were found to
      be more sensitive and highly susceptible to F toxicosis and revealed the maximum
      prevalence (92.2 %) of dental fluorosis. This indicates that bovine calves are
      less tolerant and give early sign of F poisoning (dental fluorosis) and
      therefore, they can be considered as bio-indicators for fluoridated water as well
      as for endemicity of osteo-dental fluorosis. Causes for variation in
      susceptibility to F toxicosis (fluorosis) in various species of domestic animal
      are also discussed. 

PMID- 24671614
TI  - Chemical and biological recovery from acid deposition within the Honnedaga Lake
      watershed, New York, USA.
AB  - Honnedaga Lake in the Adirondack region of New York has sustained a heritage
      brook trout population despite decades of atmospheric acid deposition.
      Detrimental impacts from acid deposition were observed from 1920 to 1960 with the
      sequential loss of acid-sensitive fishes, leaving only brook trout extant in the
      lake. Open-lake trap net catches of brook trout declined for two decades into the
      late 1970s, when brook trout were considered extirpated from the lake but
      persisted in tributary refuges. Amendments to the Clean Air Act in 1990 mandated
      reductions in sulfate and nitrogen oxide emissions. By 2000, brook trout had re
      colonized the lake coincident with reductions in surface-water sulfate, nitrate,
      and inorganic monomeric aluminum. No changes have been observed in surface-water
      acid-neutralizing capacity (ANC) or calcium concentration. Observed increases in
      chlorophyll a and decreases in water clarity reflect an increase in phytoplankton
      abundance. The zooplankton community exhibits low species richness, with a
      scarcity of acid-sensitive Daphnia and dominance by acid-tolerant copepods. Trap
      net surveys indicate that relative abundance of adult brook trout population has
      significantly increased since the 1970s. Brook trout are absent in 65 % of
      tributaries that are chronically acidified with ANC of <0 MUeq/L and toxic
      aluminum levels (>2 MUmol/L). Given the current conditions, a slow recovery of
      chemistry and biota is expected in Honnedaga Lake and its tributaries. We are
      exploring the potential to accelerate the recovery of brook trout abundance in
      Honnedaga Lake through lime applications to chronically and episodically
      acidified tributaries. 

PMID- 24671616
TI  - Elemental uptake and distribution of nutrients in avocado mesocarp and the impact
      of soil quality.
AB  - The distribution of 14 elements (both essential and non-essential) in the Hass
      and Fuerte cultivars of avocados grown at six different sites in KwaZulu-Natal,
      South Africa, was investigated. Soils from the different sites were concurrently
      analysed for elemental concentration (both total and exchangeable), pH, organic
      matter and cation exchange capacity. In both varieties of the fruit,
      concentrations of the elements Cd, Co, Cr, Pb and Se were extremely low with the
      other elements being in decreasing order of Mg > Ca > Fe > Al > Zn > Mn > Cu > Ni
      > As. Nutritionally, avocados were found to be a good dietary source of the
      micronutrients Cu and Mn. In soil, Pb concentrations indicated enrichment
      (positive geoaccumuluation indices) but this did not influence uptake of the
      metal by the plant. Statistical analysis was done to evaluate the impact of soil
      quality parameters on the nutrient composition of the fruits. This analysis
      indicated the prevalence of complex metal interactions at the soil-plant
      interface that influenced their uptake by the plant. However, the plant
      invariably controlled metal uptake according to metabolic needs as evidenced by
      their accumulation and exclusion. 

PMID- 24671617
TI  - Appearance of aldehydes in the surface layer of lake waters.
AB  - The paper presents results concerning the changes in the content of aldehydes in
      samples of lake water collected near the lake surface. The study of lake waters
      was undertaken to explain which physicochemical parameters of the environment
      have the greatest influence on the level of aldehydes, which of the aldehydes are
      most often met in surface water and in what concentrations. We observed that
      formaldehyde, acetaldehyde, propanal, glyoxal, methylglyoxal and acetone were
      commonly present in surface water samples, while semi-volatile and poorly soluble
      aldehydes such as nonanal and decanal were observed seasonally. The contents of
      total aldehydes varied in a wide range, from 55 to 670 MUg/l, and the
      concentration of total organic carbon varied significantly from 3 to 18 mg /l,
      but there was no evident correlation between them in all of samples. The total
      content of aldehydes did not depend on the meteorological parameters such as air
      temperature, UV radiation and ozone concentration; however, it was noted that the
      level of carbonyl concentration is related to the period of intense
      precipitation: in the period of very low precipitations, the highest contents of
      total aldehydes were determined in all of the water samples, and in the periods
      of intense precipitations, the content of total aldehydes was drastically
      smaller. 

PMID- 24671618
TI  - Is the tree of life the best metaphor, model, or heuristic for phylogenetics?

PMID- 24671619
TI  - Standard sister clade comparison fails when testing derived character States.
AB  - Comparing species richness in sister clades that differ in a character state is
      one of the ways to study factors influencing diversification. While most of its
      applications have focussed on traits that increase diversification, some have
      been used to study the association of a trait with lower species richness, e.g.,
      the occurrence of dioecy in flowering plants. We show here, using simulations and
      an analytical model, that the null expectation of equal species richness that is
      generally used in sister clade comparisons is wrong in the case of a derived
      trait occurring independently from speciation: one should expect fewer species in
      the clade with the derived character state when there is no difference in
      diversification rates. This is due to the waiting time for the derived state to
      appear, which causes it to occur more often on longer branches. This has the
      important implication that the probability for a clade to possess the derived
      state depends on the tree geometry, and thus on species richness: species-poorer
      clades are more likely to possess the derived state. We develop a statistical
      test for sister clade comparisons to study the effect of a derived character
      state. Applying it to a data set of dioecious clades, we find that we cannot
      confirm earlier work that concluded that dioecy decreases diversification; on the
      contrary, it seems to be associated to higher species richness than expected.
      [angiosperms; dioecy; diversification; sister clades; species richness.]. 

PMID- 24671620
TI  - Comparative assessment of selected metals in the scalp hair and nails of lung
      cancer patients and controls.
AB  - Lung cancer is seriously threatening human health and exposure to trace metals is
      the most important aetiology for lung cancer. Selected essential/toxic metals
      (Ca, Mg, Na, K, Fe, Zn, Cu, Sr, Li, Co, Mn, Ni, Cr, Cd and Pb) are measured in
      the scalp hair and nails of lung cancer patients and controls by atomic
      absorption spectrophotometric method employing nitric acid-perchloric acid-based
      wet digestion. Average concentrations of Pb, Cd, Mn, Co and Cu are found to be
      significantly higher (p < 0.05) in the scalp hair and nails of lung cancer
      patients compared with the controls, however, appreciably higher concentrations
      of Zn, Ca, Na, Mg and Cr are noted in the scalp hair of the controls. Most of the
      metal levels reveal higher dispersion and asymmetry in the scalp hair/nails of
      the patients compared with the controls. Average metal levels are also compared
      to investigate probable differences based on sex, abode, food and smoking habits.
      The correlation study shows significantly diverse mutual variations of the metals
      in the scalp hair and nails of the patients and controls. Considerable variations
      in the metal levels are also noted for various stages and types of lung cancer
      (adenocarcinoma, squamous cell carcinoma, large cell carcinoma and small cell
      lung cancer). Multivariate apportionment of the metals in the scalp hair and
      nails of the patients and controls are also significantly diverse. The study
      reveals considerably divergent variations in the metal levels in lung cancer
      patients in comparison with healthy subjects. 

PMID- 24671621
TI  - Relationships of hair mineral concentrations with insulin resistance in metabolic
      syndrome.
AB  - Mineral deficiencies can cause impaired insulin release and insulin resistance.
      This study was conducted to investigate the relationship between hair mineral
      concentrations and insulin resistance in patients with metabolic syndrome (MS). A
      total of 456 subjects (161 patients with MS and 295 subjects without MS) were
      reviewed, and fasting plasma glucose, triglycerides, HDL-cholesterol, homeostasis
      assessment model-insulin resistance (HOMA-IR), and hair mineral concentrations
      were analyzed. While hair sodium and potassium concentrations were significantly
      higher, the hair calcium, magnesium, and zinc concentrations were lower in the MS
      group than in the control group. Regarding toxic element measurements, the hair
      arsenic (As) and lead (Pb) concentrations were higher in the MS group than in the
      control group. The results of multiple regression analysis, after adjusting for
      age, showed significant relationships between the Na/Mg and Ca/P ratios and HOMA
      IR (R (2) = 0.109, p < 0.05). The Ca, Na, K, and B concentrations were also
      associated with HOMA-IR (R (2) = 0.116, p < 0.05). The hair Na concentration was
      significantly associated with MS, even after adjusting for age, visceral adipose
      tissue, and HOMA-IR (OR 1.020; 95 % CI 1.001-1.040; p = 0.036). Our findings
      suggest that hair mineral concentrations, such as calcium, magnesium, zinc,
      sodium, and potassium concentrations, may play a role in the development of
      insulin resistance. 

PMID- 24671622
TI  - Why patients seek bariatric surgery: does insurance coverage matter?
AB  - Despite increasing prevalence of bariatric surgery, little is known about why
      patients seek out this treatment option. Heads Up is an observational study
      sponsored by a large benefits management group that examines surgical and
      nonsurgical approaches to weight management in obese adults. This study examined
      patients' reasons for choosing surgery. The sample included 360 adult obese
      patients seeking bariatric surgery who were invited to volunteer for a surgical
      or a medical weight loss program by their insurer. Participants rank ordered
      their top three reasons as a deciding factor for choosing to consider surgery.
      The top three reasons were concerns regarding health (52%), current obesity
      related medical conditions (28%), and improved physical fitness (5%). Overall,
      13% endorsed insurance coverage as one of their top three choices. When insurance
      coverage is assured, health and functionality issues were the major reasons
      reported for obese adults choosing to undergo bariatric surgery.

PMID- 24671623
TI  - Mass spectrometry in plant metabolomics strategies: from analytical platforms to
      data acquisition and processing.
AB  - Covering: up to 2013. Plant metabolomics is a relatively recent research field
      that has gained increasing interest in the past few years. Up to the present day
      numerous review articles and guide books on the subject have been published. This
      review article focuses on the current applications and limitations of the modern
      mass spectrometry techniques, especially in combination with electrospray
      ionisation (ESI), an ionisation method which is most commonly applied in
      metabolomics studies. As a possible alternative to ESI, perspectives on matrix
      assisted laser desorption/ionisation mass spectrometry (MALDI-MS) in metabolomics
      studies are introduced, a method which still is not widespread in the field. In
      metabolomics studies the results must always be interpreted in the context of the
      applied sampling procedures as well as data analysis. Different sampling
      strategies are introduced and the importance of data analysis is illustrated in
      the example of metabolic network modelling.

PMID- 24671624
TI  - Benzylisoquinoline alkaloid biosynthesis in opium poppy.
AB  - Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants
      and remains the only commercial source for the narcotic analgesics morphine,
      codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The
      plant also produces several other benzylisoquinoline alkaloids with potent
      pharmacological properties including the vasodilator papaverine, the cough
      suppressant and potential anticancer drug noscapine and the antimicrobial agent
      sanguinarine. Opium poppy has served as a model system to investigate the
      biosynthesis of benzylisoquinoline alkaloids in plants. The application of
      biochemical and functional genomics has resulted in a recent surge in the
      discovery of biosynthetic genes involved in the formation of major
      benzylisoquinoline alkaloids in opium poppy. The availability of extensive
      biochemical genetic tools and information pertaining to benzylisoquinoline
      alkaloid metabolism is facilitating the study of a wide range of phenomena
      including the structural biology of novel catalysts, the genomic organization of
      biosynthetic genes, the cellular and sub-cellular localization of biosynthetic
      enzymes and a variety of biotechnological applications. In this review, we
      highlight recent developments and summarize the frontiers of knowledge regarding
      the biochemistry, cellular biology and biotechnology of benzylisoquinoline
      alkaloid biosynthesis in opium poppy. 

PMID- 24671626
TI  - Detection and localization of novel hordatine-like compounds and glycosylated
      derivates of hordatines by imaging mass spectrometry of barley seeds.
AB  - Mass spectrometry imaging was applied on germinated barley for the detailed
      localization of metabolites in longitudinal and transversal seed sections. Among
      others, 20 m/z signals occurred in three regular peak clusters with specific,
      distinct localizations in embryo tissues. High resolution FT-ICR MS, MALDI-TOF
      MS/MS, and UHPLC-ESI MS/MS served for the identification and structural
      characterization of these compounds. Only five metabolites were published in
      their structures, namely the antifungal compounds hordatine A and B in non
      glycosylated and glycosylated forms. All other non-identified cluster compounds
      were of hordatine-like structure and differed by systematic O-methylations,
      hydroxylations, and glycosylations. These differences in molecular structures
      correlated to distinct localization patterns within the embryo and might serve
      for the regulation of antifungal properties. Based on the structural
      investigations by mass spectrometry, an array of different hordatines that
      comprises the five published hordatines, 15 novel hordatine derivates and their
      six precursors could be localized in the embryo of germinated barley.
      Implications for the biosynthetic pathway and transport processes are discussed.

PMID- 24671627
TI  - Spectroscopic dimensions of silver nanoparticles and clusters in ZnO matrix and
      their role in bioinspired antifouling and photocatalysis.
AB  - Silver doped zinc oxide nanoparticles are synthesized by a solution combustion
      method. The samples characterized by a variety of spectroscopic and other
      techniques clearly reveal the presence of silver nanoparticles as well as silver
      clusters. The silver in the two forms was identified by careful deconvolution of
      X-ray photoelectron spectral results. Their formation was also confirmed by the
      presence of plasmons, the concentration and energy of which increase on
      increasing silver input, indicating the presence of perpendicular excitons since
      aggregates of clusters are known to shift the plasmon resonances depending on
      their topologies. Further confirmation of clusters came from EPR (electron
      paramagnetic resonance), HRSEM (high resolution scanning electron microscopy) and
      HRTEM (high resolution transmission electron microscopy); direct proof for
      clusters came from matrix assisted laser desorption ionization-time of flight
      (MALDI-TOF) mass spectral measurements. The antimicrobial activity of the silver
      doped zinc oxide polymer nanocomposites as biomedical devices are measured by
      zone of inhibition. Also, samples coated on paper disk with acacia binder are
      evaluated by a disk diffusion method. While pure zinc oxide does not show any
      antimicrobial property, the activity of silver-doped zinc oxide is comparable to
      that of commercial antibiotics and found to be related to nanoparticulate silver.
      Similarly, the microbial adherence to the surface of polymer nanocomposite which
      mimics a biomedical device also was influenced by nanoparticles of silver. The
      photocatalytic water treatment was carried out using silver carrying
      nanoparticles with Rhodamine-B and 4-chlorophenol as model pollutants. The
      increased photocatalytic activity of silver containing zinc oxide as compared to
      pure zinc oxide nanoparticles is attributed to the synergistic display of the
      properties of silver nanoparticles and clusters in zinc oxide. This activity
      depends upon the dispersion of silver nanoparticles over the zinc oxide lattice
      where charge separation plays a dominant role. The mechanisms for both
      photocatalysis and antimicrobial activity are discussed. 

PMID- 24671628
TI  - Chronic neuronopathic type of Gaucher's disease with progressive myoclonic
      epilepsy in the absence of visceromegaly and bone involvement.
AB  - INTRODUCTION: Gaucher's disease is a lysosomal storage disorder caused by the
      deficiency of glucocerebrosidase. Gaucher's disease has three clinical types: non
      neuronopathic (Type 1), Acute Neuropathic (Type 2) and chronic neuronopathic
      (Type 3). The chronic neuronopathic (Type 3) is characterised by a variety of
      disease variants with onset in childhood with hepatomegaly, skeletal lesions and
      later slow horizontal saccades, treatment-resistant generalised tonic-clonic and
      myoclonic seizures, dementia, progressive spasticity, cognitive deterioration,
      ataxia and death in the second or third decade of life. CASE PRESENTATION: We
      describe a case of a 17-year-old girl who was born normally but subsequently
      developed treatment-refractory seizures at the age of nine with myoclonus,
      oculomotor apraxia, ataxia and cognitive decline. Enzyme activity of beta
      glucocerebrosidase was found to be low without visceromegaly or bone involvement.
      CONCLUSION: Screening for lysosomal enzyme activity should be done in patients
      exhibiting features suggestive of progressive myoclonic epilepsy.

PMID- 24671629
TI  - Public health and the Transatlantic Trade and Investment Partnership.

PMID- 24671630
TI  - Why the European Journal of Public Health will no longer publish tobacco industry
      supported research.

PMID- 24671625
TI  - Plant systems biology: insights, advances and challenges.
AB  - Plants dwelling at the base of biological food chain are of fundamental
      significance in providing solutions to some of the most daunting ecological and
      environmental problems faced by our planet. The reductionist views of molecular
      biology provide only a partial understanding to the phenotypic knowledge of
      plants. Systems biology offers a comprehensive view of plant systems, by
      employing a holistic approach integrating the molecular data at various
      hierarchical levels. In this review, we discuss the basics of systems biology
      including the various 'omics' approaches and their integration, the modeling
      aspects and the tools needed for the plant systems research. A particular
      emphasis is given to the recent analytical advances, updated published examples
      of plant systems biology studies and the future trends.

PMID- 24671632
TI  - Adenosine triphosphate concentrations are higher in the brain of APOE3- compared
      to APOE4-targeted replacement mice and can be modulated by curcumin.
AB  - Curcumin from Curcuma longa may exert putative neuroprotective properties in the
      brain. Impaired mitochondrial function is implicated in Alzheimer's disease and
      the presence of the apolipoprotein (APO) E4 genotype, which is a risk factor for
      late-onset Alzheimer's disease, may aggravate mitochondrial malfunction. Here, we
      report that in the brain of 16-month-old APOE4-targeted replacement mice,
      adenosine triphosphate (ATP) concentrations were significantly lower than in
      APOE3 mice. A 3-month dietary supplementation of 0.2 % curcumin numerically
      increased ATP concentrations in APOE3 and significantly in APOE4 mice compared to
      the respective controls. Curcumin significantly induced the transcription of
      peroxisome proliferator-activated receptor (PPAR) gamma and mitochondrial
      transcription factor A (TFAM) in APOE3, but not in APOE4 mice. Moreover,
      PPARgamma coactivator (PGC)-1alpha and guanine-adenine repeat binding protein
      alpha (GABPa) mRNA was only increased in APOE3 mice. Consistent with these
      observations, protein expression of mitochondrial respiratory complexes,
      especially of complex IV, also appeared to be increased in APOE3 mice. In
      conclusion, we provide evidence that curcumin affects mitochondrial function and
      gene and protein expression in the murine brain despite its low bioavailability
      and carriers of the Alzheimer's disease-risk genotype APOE4 may be less
      responsive to dietary curcumin than APOE3 carriers. 

PMID- 24671633
TI  - [Combination of different techniques for secondary anchoring of intraocular
      lenses].
AB  - BACKGROUND: The four fundamental techniques of secondary intraocular lens (IOL)
      fixation, namely sulcus placement, scleral or iris suture fixation and scleral
      haptic fixation can be combined in special situations. AIM: When is a combination
      of different techniques advisable? METHODS: This article describes our
      experiences and gives an example of combined technique use. RESULTS: These
      situations arise in cases when neighboring ocular structures are only partially
      preserved or show particular distinctive defects that can be repaired at the time
      of secondary IOL anchoring. This article presents a case of IOL-induced iris
      chafing and traumatic iridodialysis which was closed by a combined technique of
      iris suture and scleral suture fixation. CONCLUSION: A combination of different
      anchoring techniques for secondary IOL implantation can achieve a simultaneous
      repair of perilenticular structures and reduce the amount of suture material
      used.

PMID- 24671635
TI  - Access to and use of marine genetic resources: understanding the legal framework.
AB  - With the adoption of the Nagoya Protocol in 2010, an additional legal instrument
      under the Convention on Biological Diversity (1992), the legal landscape
      surrounding the access to and utilization of genetic resources will change. This
      is likely to impact working procedures for scientists, turning pre-existing
      ethics into legal obligations. The aim of this article is to inform scientists on
      the global access and benefit-sharing framework which has been set by the
      Convention on Biological Diversity and its Nagoya Protocol, focusing specifically
      on their application to marine genetic resources for which the United Nations
      Convention on the Law of the Sea (1982) also has relevance. 

PMID- 24671634
TI  - [Femtosecond laser-assisted lens surgery depending on interface design and laser
      pulse energy: results of the first 200 cases].
AB  - BACKGROUND: This study was designed to evaluate the effectiveness and safety of
      femtosecond laser-assisted lens surgery depending on interface design and laser
      pulse energy settings. METHODS: In this non-randomized, consecutive case
      series200 eyes underwent femtosecond laser-assisted (LenSx, Alcon) lens surgery
      between November 2012 and June 2013. Group 1 consisted of 85 eyes with 60
      cataracts and 25 refractive lens exchanges (RLE) which were treated with a curved
      direct contact interface, and group 2 consisting of 115 eyes with 72 cataracts
      and 43 RLEs treated with a modified interface using an additional soft contact
      lens (SoftFitTM, Alcon) between the corneal surface and the interface. The degree
      of opacity of the lens in cataract eyes was measured with a Scheimpflug camera.
      Afterwards, phacoemulsification was performed with intraocular lens (IOL)
      implantation in all eyes. Primary endpoints were the effective
      phacoemulsification time (EPT), the average laser treatment time and the
      occurrence of intraoperative complications. RESULTS: The mean EPT in group 1 was
      1.62 +/- 1.12 s (cataract 1.94 +/- 1.31 s, RLE 1.29 +/- 1.01 s) and in group 2
      the mean EPT was 1.66 +/- 0.92 s (cataract 1.98 +/- 1.28 s, RLE 1.33 +/- 1.22 s,
      p = 0.32 between groups). The laser treatment lasted on average 48.90 +/- 2.45 s
      (group 1) and 49.70 +/- 2.87 s (group 2) with an average lens fragmentation
      thickness of 3401.48 +/- 401.12 um (all groups). In four cases of group 1, a
      second applanation of the interface was necessary. Furthermore, one anterior
      capsule tear, 39 cases of intraoperative wrinkling of the corneal surface and 21
      cases in which the corneal incision had to be opened manually were documented in
      group 1. In group 2 no second applanation of the interface, no anterior capsule
      tears and no corneal wrinkling but 9 cases with a manual opening of corneal
      incisions were documented (p < 0.01 between groups). CONCLUSION: The minor
      intraoperative complications of the femtosecond laser technique investigated
      could be significantly reduced using an optimized interface and reduced laser
      pulse energy.

PMID- 24671636
TI  - The relation between the genetic architecture of quantitative traits and long
      term genetic response.
AB  - The genetic architecture of a quantitative trait refers to the number of genetic
      variants, allele frequencies, and effect sizes of variants that affect a trait
      and their mode of gene action. This study was conducted to investigate the effect
      of four shapes of allelic frequency distributions (constant, uniform, L-shaped
      and U-shaped) and different number of trait-affecting loci (50, 100, 200, 500) on
      allelic frequency changes, long term genetic response, and maintaining genetic
      variance. To this end, a population of 440 individuals composed of 40 males and
      400 females as well as a genome of 200 cM consisting of two chromosomes and with
      a mutation rate of 2.5 * 10(-5) per locus was simulated. Selection of superior
      animals was done using best linear unbiased prediction (BLUP) with assumption of
      infinitesimal model. Selection intensity was constant over 30 generations of
      selection. The highest genetic progress obtained when the allelic frequency had L
      shaped distribution and number of trait-affecting loci was high (500). Although
      quantitative genetic theories predict the extinction of genetic variance due to
      artificial selection in long time, our results showed that under L- and U-shapped
      allelic frequency distributions, the additive genetic variance is persistent
      after 30 generations of selection. Further, presence or absence of selection
      limit can be an indication of low (<50) or high (>100) number of trait-affecting
      loci, respectively. It was concluded that the genetic architecture of complex
      traits is an important subject which should be considered in studies concerning
      long-term response to selection. 

PMID- 24671637
TI  - Matched pair analysis to examine the effects of a planned preoperative exercise
      program in early gastric cancer patients with metabolic syndrome to reduce
      operative risk: the Adjuvant Exercise for General Elective Surgery (AEGES) study
      group.
AB  - BACKGROUND: Because obesity is a risk factor during surgery, the effects of a
      preoperative exercise program to reduce the incidence of peri- and postoperative
      complications in patients with a high body mass index (>25 kg/m(2)) and metabolic
      syndrome were investigated. An assessment of the effects of prospectively planned
      preoperative exercise was performed in a prospective matching study comparing an
      exercise testing group and a usual preoperative preparation group who underwent
      gastrectomy for gastric cancer in Japan. METHODS: Stage I gastric cancer patients
      with metabolic syndrome diagnosed according to the criteria of the Japanese
      Ministry of Health, Labor, and Welfare underwent surgery after preoperative
      exercise. The control group was selected from a database using an individual
      matching approach for surgery, sex, weight, body mass index, volume of visceral
      fat, and institution. The primary end point was the frequency of postoperative
      complications such as cardiovascular events, pneumonia, and surgery-related
      abdominal complications. RESULTS: Data from a total of 72 patients (54 in the
      surgery-alone group, 18 in the preoperative exercise group) were analyzed. The
      median operative time and amount of bleeding were 208 min and 130 ml in the
      surgery-alone group and 248 min and 105 ml in the exercise group, respectively.
      Postoperative complications occurred in one case (5.5 %) in the exercise group
      and 22 (40.7 %) cases in the surgery-alone group. CONCLUSIONS: Preoperative
      exercise is safe, and its benefits in reducing postoperative complications are
      promising and therefore warrant further investigation.

PMID- 24671638
TI  - Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and
      effective option for colorectal cancer patients after emergency surgery in the
      presence of peritoneal carcinomatosis.
AB  - BACKGROUND: When peritoneal carcinomatosis (PC) is diagnosed during emergency
      surgery for colorectal cancer (CRC), further treatment with curative intent may
      seem futile given the known poor prognosis of both PC and emergency surgery. The
      aim of the current study was to investigate the feasibility and effectiveness of
      cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      for CRC patients who previously underwent emergency surgery in the presence of
      PC. METHODS: All patients with synchronous PC of CRC referred to two tertiary
      centers between April 2005 and November 2013 were included in this study.
      Operative, postoperative and survival details were compared between patients
      presenting in an emergency or elective setting. RESULTS: In total, 149 patients
      with synchronous PC underwent CRS and HIPEC. Amongst these patients, 36 (24.2 %)
      initially presented with acute symptoms requiring emergency surgery. Acute
      presentation did not result in a longer interval between the initial operation
      and HIPEC (2.2 vs. 2.1 months; P = 0.09). When comparing operative outcomes, no
      significant differences were found in blood loss (P = 0.47), operation time (P =
      0.39), or completeness of cytoreduction (P = 0.97). In addition, complication
      rates, degree and types of complication did not differ between the groups. Median
      survival was 36.1 months for emergency presentation compared with 32.1 in the
      elective group (P = 0.73). CONCLUSION: CRS + HIPEC may be performed safely in
      patients with PC of colorectal origin presenting with acute symptoms requiring
      emergency surgery. More importantly, the 5-year survival rate in these patients
      was equal to elective cases. This should be regarded as promising and therefore
      considered for these patients.

PMID- 24671639
TI  - Innovative rapid gene methylation analysis of surgical margin tissues in head and
      neck cancer.
AB  - BACKGROUND: Securing the negative surgical margin is the first step in surgical
      cancer treatment. However, tumor recurrence sometimes occurs even with
      histologically negative surgical margins. To detect minimal residual cancer cells
      in the deep margin intraoperatively, a time-efficient molecular approach is
      required. METHODS: We established an innovative rapid quantitative methylation
      PCR (QMSP) assay, which consists of substantially time-minimized DNA extraction,
      bisulfite treatment, and QMSP assays. To demonstrate the feasibility of this
      procedure, 10 serial surgical specimens of primary head and neck squamous cell
      carcinoma (HNSCC) were evaluated by both rapid and conventional QMSP. Two
      frequently methylated genes in head and neck cancer, homeobox A9 (HOXA9) and
      endothelin receptor type B (EDNRB) were analyzed in 10 HNSCCs and surgical margin
      tissues, as well as normal muscle and oral mucosa samples. RESULTS: The product
      quality of DNA extraction and bisulfite treatment using the time-saving procedure
      was comparable to the conventional procedure. In the QMSP assay, target gene
      methylation and reference gene methylation were equally detected by both the
      rapid and conventional method. Finally, relative results of rapid and
      conventional QMSP were quite similar to each other in tumors, margins, and normal
      tissues. The average total time required for the rapid QMSP procedure was less
      than 3 h and could be accomplished by a single person. CONCLUSION: From the
      viewpoint of accuracy, cost, and time consumption, the innovative rapid QMSP
      maintains highly sensitive methylation detection accomplished within the time
      frame of a major ablative and reconstructive procedure.

PMID- 24671640
TI  - Oral pigmentation in McCune-Albright syndrome.
AB  - IMPORTANCE: The differential diagnosis for oral lentigines includes several
      syndromes with important associated systemic findings. McCune-Albright syndrome
      (MAS), a mosaic condition associated with cafe au lait pigmentation, is not
      typically considered a mucosal lentiginosis syndrome. The clinical phenotype of
      MAS is variable because of mosaicism, but oral pigmentation developing in mid
      childhood to early adulthood should be recognized as a clinical feature of MAS.
      OBSERVATIONS: We present 4 patients with MAS who developed oral mucosal
      pigmentation during childhood or early adulthood. All patients had other
      characteristic findings of MAS including hyperfunctioning endocrinopathies,
      polyostotic fibrous dysplasia, and cafe au lait pigmentation. CONCLUSIONS AND
      RELEVANCE: Oral pigmentation is an underrecognized finding in MAS and presents
      later in development compared with the other mucosal lentiginosis syndromes. The
      diagnosis of MAS is most commonly a clinical diagnosis because mutational
      analysis is challenging in mosaic conditions. Expanding the cutaneous phenotype
      to include oral pigmentation further characterizes the clinical findings in this
      mosaic condition, broadens the differential diagnosis of syndromes with oral
      pigmentation, and in some cases may aid in earlier diagnosis of MAS.

PMID- 24671643
TI  - Engineering photosynthetic organisms for the production of biohydrogen.
AB  - Oxygenic photosynthetic organisms such as green algae are capable of absorbing
      sunlight and converting the chemical energy into hydrogen gas. This process takes
      advantage of the photosynthetic apparatus of these organisms which links water
      oxidation to H2 production. Biological H2 has therefore the potential to be an
      alternative fuel of the future and shows great promise for generating large scale
      sustainable energy. Microalgae are able to produce H2 under light anoxic or dark
      anoxic condition by activating 3 different pathways that utilize the hydrogenases
      as catalysts. In this review, we highlight the principal barriers that prevent
      hydrogen production in green algae and how those limitations are being addressed,
      through metabolic and genetic engineering.  We also discuss the major challenges
      and bottlenecks facing the development of future commercial algal photobiological
      systems for H2 production. Finally we provide suggestions for future strategies
      and potential new techniques to be developed towards an integrated system with
      optimized hydrogen production. 

PMID- 24671644
TI  - Oral immunotherapy for food allergy, ready for prime time? Heated egg and milk.
AB  - Cow's milk and hen's egg allergies are two of the most common food allergies that
      affect children, with an estimated prevalence of 2-3 % each. Persistence of food
      allergy into late teen years and adulthood is being increasingly recognized,
      possibly due to strict avoidance practices. Heating has been known to alter food
      allergenicity, and the majority of milk- and egg-allergic patients tolerate
      heated forms of those foods. Heated milk and heated egg have been increasingly
      studied as oral immunotherapy (OIT) for treatment of milk and egg allergy. While
      heated milk and heated egg have been shown to be safe in selected milk- and egg
      allergic cohorts, larger studies are needed to predict which patients are optimal
      candidates for this strategy and to further clarify whether ingestion of heated
      milk or heated egg truly accelerates the onset of clinical tolerance to unheated
      forms of these foods. 

PMID- 24671641
TI  - EGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy.
AB  - Glioblastoma is a particularly resilient cancer, and while therapies may be able
      to reach the brain by crossing the blood-brain barrier, they then have to deal
      with a highly invasive tumor that is very resistant to DNA damage. It seems clear
      that in order to kill aggressive glioma cells more efficiently and with fewer
      side effects on normal tissue, there must be a shift from classical cytotoxic
      chemotherapy to more targeted therapies. Since the epidermal growth factor
      receptor (EGFR) is altered in almost 50% of glioblastomas, it currently
      represents one of the most promising therapeutic targets. In fact, it has been
      associated with several distinct steps in tumorigenesis, from tumor initiation to
      tumor growth and survival, and also with the regulation of cell migration and
      angiogenesis. However, inhibitors of the EGFR kinase have produced poor results
      with this type of cancer in clinical trials, with no clear explanation for the
      tumor resistance observed. Here we will review what we know about the expression
      and function of EGFR in cancer and in particular in gliomas. We will also
      evaluate which are the possible molecular and cellular escape mechanisms. As a
      result, we hope that this review will help improve the design of future EGFR
      targeted therapies for glioblastomas.

PMID- 24671642
TI  - Alcoholic cardiomyopathy: pathophysiologic insights.
AB  - Alcoholic cardiomyopathy (ACM) is a specific heart muscle disease found in
      individuals with a history of long-term heavy alcohol consumption. ACM is
      associated with a number of adverse histological, cellular, and structural
      changes within the myocardium. Several mechanisms are implicated in mediating the
      adverse effects of ethanol, including the generation of oxidative stress,
      apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements
      in fatty acid metabolism and transport, and accelerated protein catabolism. In
      this review, we discuss the evidence for such mechanisms and present the
      potential importance of drinking patterns, genetic susceptibility, nutritional
      factors, race, and sex. The purpose of this review is to provide a mechanistic
      paradigm for future research in the area of ACM. 

PMID- 24671645
TI  - Sporoderm and tapetum development in Eupomatia laurina (Eupomatiaceae). An
      interpretation.
AB  - For the first time, the developmental events in the course of exine structure
      establishment have been traced in detail with TEM in Eupomatia, with the addition
      of cytochemical tests. A new look at unfolding events is suggested using our
      recent hypothesis on self-assembling micellar mesophases. The process proved to
      be unusual and includes "ghost" stages. The first units observed in the
      periplasmic space are spherical ones (= normal spherical micelles). These
      accumulate, resulting in a granular layer up to middle tetrad stage.
      Sporopollenin precursor accumulation on these units makes the ectexine layer
      looking as homogenous at late tetrad stage. Simultaneously, the columns of
      globules are added in the periplasmic space, which reminds an attempt to form
      columellae; but, the process failed. Instead, a fimbrillate endexine layer of
      compressed globules appears. The latter augments via additional globules,
      appearing in the periplasmic space in the free microspore period. The endexine
      formation is double-stepped spatially and temporally. The second, lamellate
      endexine layer (laminate micelles) appears late in development, when the
      channeled intine-I is already established-a very unusual feature. Moreover, a
      "fenestrated" stage comes unexpectedly at vacuolate stage, when hitherto
      amorphous ectexine appears pierced by cavernae-the results of reversal of normal
      spherical micelles (constituents of ectexine) to reverse the ones that open their
      cores for the entrance of hydrophilic nutrients from tapetum and give them over
      to the microspore cytoplasm by exchanging their solubilizates.

PMID- 24671648
TI  - Theoretical insight into chlorine adsorption on the Fe(100) surface.
AB  - This study represents a detailed DFT periodic-slab study on the interaction
      between atomic chlorine and the Fe(100) surface. Energetic and structural
      parameters are calculated for a wide range of coverages corresponding to top,
      bridge and hollow pure on-surface adsorptions. Calculated chemisorbed energies
      are found to increase gradually with the degree of coverage. Formation of iron
      chlorides via substitutional adsorption is predicted to be not feasible in view
      of the calculated chemisorption energies. This finding is in line with earlier
      experimental measurements with regard to the absence of chlorine diffusion into
      bulk Fe. Sublimation energies for FeCl2 and FeCl3 are estimated and discussed to
      elucidate the fate of the chlorine-iron thin layer. A stability temperature
      pressure diagram is constructed for a wide range of chlorine chemical potentials
      to mimic real operational conditions. 

PMID- 24671646
TI  - Electron tomographic analysis of cytokinesis in the brown alga Silvetia
      babingtonii (Fucales, Phaeophyceae).
AB  - In brown algae, membrane resources for the new cell partition during cytokinesis
      are mainly flat cisternae (FCs) and Golgi-derived vesicles. We used electron
      tomography coupled with rapid freezing/freeze substitution of zygotes to clarify
      the structure of transient membrane compartments during cytokinesis in Silvetia
      zygotes. After mitosis, an amorphous membranous structure, considered to be an FC
      intermediate was observed near endoplasmic reticulum clusters, lying between two
      daughter nuclei. FCs were arrayed at the cytokinetic plane, and a tubular
      membranous network was formed around them. This network might be formed by the
      consecutive fusion of spherical vesicles that are linked to the edges of FCs to
      form a membranous network (MN). At the initial stage of the formation of a
      membranous sac (MS) from the MN, the MS had flat and swollen parts, with the
      latter showing membranous tunnels. Coated pits were detected with high frequency
      at the swollen parts of the MS. This observation indicated that membranous
      tunnels disappeared by recycling of excess membrane via endocytosis, and the
      swollen part became flat. The MN appeared at the edges of the growing MS. MN and
      the MN-MS complex were observed along the cytokinetic plane in several spaces.
      The MS expanded by the incorporation of MN or other MS in its neighborhood. With
      the maturation of the new cell partition membrane, the thickness of the MS became
      constant and the membrane cavity disappeared. The changes in the surface area and
      volume of the transient membrane compartment during cytokinesis were analyzed
      from the tomographic data.

PMID- 24671647
TI  - Placental C4d as a common feature of chromosomally normal and abnormal
      miscarriages.
AB  - Placental C4d deposition is a feature of classical complement pathway activation
      and has been documented in various obstetrical settings. However, it is unknown
      whether placental C4d deposition is present in miscarriages and its frequency is
      different between chromosomally normal and abnormal miscarriages. This study was
      conducted to assess villous C4d deposition in miscarriages and to determine
      whether its frequency is different between chromosomally normal and abnormal
      miscarriages. Tissue samples (N = 58) of elective abortions (n = 20),
      miscarriages with normal chromosomes (n = 15), trisomy 16 (n = 13), and trisomy
      22 (n = 10) were analyzed. Immunohistochemical staining for C4d and CD138 was
      done. Placental C4d deposition was defined as linear C4d immunoreactivity along
      the syncytiotrophoblast. Placental C4d immunoreactivity was detected in 73.3 %
      (11/15) and 56.5 % (13/23) of miscarriages with normal chromosomes and trisomy
      cases, respectively, while it was found in 5 % (1/20) of elective abortions (p <
      0.05). Placental C4d deposition was more frequent in recurrent miscarriages
      (previous spontaneous abortion >=2) than in sporadic miscarriages (76.5 vs. 30.0
      %; p = 0.001). Chronic deciduitis was observed in 20.0 % (3/15) and 30.4 % (7/23)
      of miscarriages with normal chromosomes and trisomy cases, respectively, but not
      in elective abortions (p = 0.07 and 0.01, for each). The frequencies of C4d
      deposition (46.2 vs. 70.0 %) and chronic deciduitis (38.5 vs. 20.0 %) were not
      also different between trisomy 16 and trisomy 22 cases. Placental C4d deposition
      is a prominent feature of miscarriages regardless of their chromosomal status.
      The overall findings suggest that complement-mediated placental injury is a
      common pathology of miscarriage with diagnostic values in routine pathology
      practice.

PMID- 24671650
TI  - Establishment and characterization of an ovarian cell line from Southern catfish
      (Silurus meridionalis).
AB  - An ovarian cell line was successfully developed from the juvenile ovary of
      Southern catfish (SCO1) (Silurus meridionalis), which was designated as SCO1. The
      cell line multiplied preferentially in L-15 medium with 15 % fetal bovine serum
      at 28  degrees C for more than 70 passages over a period of 420 days. SCO1 showed
      fibroblast-like morphology and predominantly retained a diploid karyotype of 58
      chromosomes. From the gene expression patterns, SCO1 showed a characteristic of
      ovarian granulosa cells. After the cells were transfected with the green
      fluorescent protein expression vector, bright fluorescent signals could be
      observed in approximately 30 % cells. This cell line may be valuable for the
      evaluation of endocrine disruptors and studying interactions between somatic
      cells and germ cells.

PMID- 24671649
TI  - Evaluation of the use of metallothionein as a biomarker for detecting
      physiological responses to mercury exposure in the bonnethead, Sphyrna tiburo.
AB  - Previous studies have demonstrated that sharks, perhaps more so than any other
      fishes, are capable of bioaccumulating the non-essential toxic metal mercury (Hg)
      to levels that threaten the health of human seafood consumers. However, few
      studies have explored the potential effects of Hg accumulation in sharks
      themselves. Therefore, the goal of this study was to examine if physiological
      effects occur in sharks in response to environmentally relevant levels of Hg
      exposure. To address this goal, the relationship between muscle Hg concentrations
      and muscle/hepatic levels of metallothionein (MT), a widely used protein
      biomarker of toxic metal exposure in fish, was examined in bonnetheads, Sphyrna
      tiburo, from three Florida estuaries. Total Hg concentrations in bonnethead
      muscle, as determined using thermal decomposition and atomic absorption
      spectrometry, ranged from 0.22 to 1.78 MUg/g wet weight and were correlated with
      animal size. These observations were consistent with earlier studies on Florida
      bonnetheads, illustrating that they experience bioaccumulation of Hg, often to
      levels that threaten the health of these animals or consumers of their meat.
      However, despite this, MT concentrations measured using Western blot analysis
      were not correlated with muscle Hg concentrations. These results suggest that
      either environmentally relevant levels of Hg exposure and uptake are below the
      physiological threshold for inducing effects in sharks or MT is a poor biomarker
      of Hg exposure in these fishes. Of these two explanations, the latter is favored
      based on a growing body of evidence that questions the use of MTs as specific
      indicators of Hg exposure and effects in fish.

PMID- 24671651
TI  - Postural sway and perception of affordances in children at risk for developmental
      coordination disorder.
AB  - Gibson (The ecological approach to visual perception, Houghton Mifflin, Boston,
      1979/1986) defined affordances as opportunities for motor behaviors, and highly
      emphasized the interaction between perception and action. Research on children
      with developmental coordination disorder commonly reports difficulties in
      judgments of affordances (perception) and in postural control (action). However,
      how perception and action are coupled has not been studied yet. The present study
      sought to evaluate the relationship between control of postural sway and
      perception of affordances in children at risk for developmental coordination
      disorder (RDCD) and typically developing children (TDC). We hypothesized that the
      relationship between perception and action would differ between groups.
      Participants made a series of judgments about their maximum sitting height
      (SHmax) while standing with and without wearing 10 cm blocks on feet. Postural
      sway and the judgment accuracy were recorded. Our findings showed that RDCD
      swayed more during judgment sessions and made less accurate judgments compared to
      TDC. In addition, TDC reduced postural sway from inter-judgment to judgment
      sessions, whereas the postural sway of RDCD remained identical between sessions.
      Last, while TDC reduced postural sway across judgment trials and revealed a
      learning effect of the judgments about SHmax in the block condition, RDCD never
      modulated postural sway and did not learn their SHmax in both non-block and block
      conditions. Overall, modulation of postural sway differed between groups during
      judgment sessions and between inter-judgment and judgment sessions, whereby their
      perceptual judgments about SHmax were differentially influenced. To summarize,
      this study demonstrated a difference in perception and action coupling between
      RDCD and TDC.

PMID- 24671652
TI  - Precursors of post-bout motion sickness in adolescent female boxers.
AB  - Athletic head trauma (both concussive and sub-concussive) is common among
      adolescents. Head trauma often is followed by motion sickness-like symptoms, by
      changes in cognitive performance, and by changes in standing body sway. We
      evaluated adolescent female boxers who did and did not report motion sickness
      after a bout (i.e., a boxing match), together with a control group of non-boxers.
      We asked whether pre-bout body sway would differ between boxers who experienced
      post-bout motion sickness and those who did not. In addition, we asked whether
      pre-bout cognitive performance would differ between non-boxers and boxers with
      and without post-bout motion sickness. Seven of twenty boxers reported motion
      sickness after a bout. Pre-bout measures of cognitive performance and body sway
      were different in boxers who reported post-bout motion sickness than in boxers
      without post-bout sickness or controls. The results suggest that susceptibility
      to motion sickness-like symptoms in adolescent female boxers may be manifested in
      characteristic patterns of body sway and cognitive performance. It may be
      possible to use pre-bout data to predict susceptibility to post-bout symptoms. 

PMID- 24671653
TI  - Proprioceptive illusions created by vibration of one arm are altered by vibrating
      the other arm.
AB  - There is some evidence that signals coming from both arms are used to determine
      the perceived position and movement of one arm. We examined whether the sense of
      position and movement of one (reference) arm is altered by increases in muscle
      spindle signals in the other (indicator) arm in blindfolded participants (n =
      26). To increase muscle spindle discharge, we applied 70-80 Hz muscle vibration
      to the elbow flexors of the indicator arm. In a first experiment, proprioceptive
      illusions in the vibrated reference arm in a forearm position-matching task were
      compared between conditions in which the indicator arm elbow flexors were
      vibrated or not vibrated. We found that the vibration illusion of arm extension
      induced by vibration of reference arm elbow flexors was reduced in the presence
      of vibration of the indicator elbow flexors. In a second experiment, participants
      were asked to describe their perception of the illusion of forearm extension
      movements of the reference arm evoked by vibration of reference arm elbow flexors
      in response to on/off and off/on transitions of vibration of non-reference arm
      elbow flexors. When vibration of non-reference arm elbow flexors was turned on,
      they reported a sensation of slowing down of the illusion of the reference arm.
      When it was turned off, they reported a sensation of speeding up. To conclude,
      the present study shows that both the sense of limb position and the sense of
      limb movement of one arm are dependent to some extent on spindle signals coming
      from the other arm.

PMID- 24671654
TI  - Response.

PMID- 24671655
TI  - Analysis of the expression of nine secreted matrix metalloproteinases and their
      endogenous inhibitors in the brain of mice subjected to ischaemic stroke.
AB  - Matrix metalloproteinases (MMPs) are a family of more than twenty secreted and
      cell-surface endopeptidases. Among them, MMP2, MMP3 and MMP9 are involved in
      blood-brain barrier injury and neuronal death after cerebral ischaemia. On the
      other hand, very little is known about the expression of the other secreted MMPs.
      Herein, we compared the global changes in MMP1, MMP2, MMP3, MMP7, MMP8, MMP9,
      MMP10, MMP12 and MMP13, and their endogenous inhibitors TIMP1 and TIMP2, both at
      the mRNA and protein levels, during the hyperacute (6 h), acute (24 h) and
      subacute (72 h) stages following transient focal cerebral ischaemia and treatment
      with recombinant tissue plasminogen activator (rtPA). We observed a significant
      increase in MMP1, MMP2, MMP9, MMP10, MMP13 and TIMP1 levels during the acute
      stage of reperfusion, which was further amplified during the subacute stage for
      MMP1, MMP2, MMP10 and TIMP1. In general, no change of MMP3, MMP7, MMP8, MMP12 and
      TIMP2 was observed. However, rtPA treatment induced a rapid increase in
      MMP1/TIMP2, MMP2/TIMP2, MMP8/TIMP2 and MMP9/TIMP2 ratios during the hyperacute
      stage of reperfusion compared to saline treatment, which may have potential
      implications in the early disruption of the blood-brain barrier after rtPA
      treatment. 

PMID- 24671656
TI  - Novel non-pharmacological approaches to heart failure.

PMID- 24671657
TI  - High performance semiconducting enriched carbon nanotube thin film transistors
      using metallic carbon nanotubes as electrodes.
AB  - High-performance solution-processed short-channel carbon nanotube (CNT) thin film
      transistors (TFTs) are fabricated using densely aligned arrays of metallic CNTs
      (m-CNTs) for the source and drain electrodes, while aligned arrays of
      semiconducting enriched CNTs (s-CNTs) are used as the channel material. The
      electrical transport measurements at room temperature show that using the m-CNT
      as the contact for the s-CNT array devices with a 2 MUm channel length performed
      superior to those where the control Pd was the contact. The m-CNT contact devices
      exhibited a maximum (average) on-conductance of 36.5 MUS (19.2 MUS), a
      transconductance of 2.6 MUS (1.2 MUS), a mobility of 51 cm(2) V(-1) s(-1) (25
      cm(2) V(-1) s(-1)), and a current on-off ratio of 1.1 * 10(6) (2.5 * 10(5)).
      These values are almost an order of magnitude higher than that of control Pd
      contact devices with the same channel length and s-CNT linear density. The low
      temperature charge transport measurements suggest that these improved
      performances are due to the m-CNT contact s-CNT devices having a lower Schottky
      barrier compared to the Pd contact s-CNT devices. We attribute this lower
      Schottky barrier to the unique geometry of our devices. In addition to using
      semiconducting enriched CNTs, our results suggest that using the metallic CNT as
      an electrode can significantly enhance the performance of CNT TFTs. 

PMID- 24671658
TI  - Joint modeling of HIV data in multicenter observational studies: A comparison
      among different approaches.
AB  - Disease process over time results from the combination of event history
      information and longitudinal process. Commonly, separate analyses of longitudinal
      and survival outcomes are performed. However, discharging the dependence between
      these components may cause misleading results. Separate analyses are difficult to
      interpret whenever one deals with observational retrospective multicenter cohort
      studies where the biomarkers are poorly monitored over time, while the survival
      component may be affected by several sources of bias, such as multiple endpoints,
      multiple time-scales, and informative censoring. We discuss how joint modeling of
      longitudinal and survival data represents an effective strategy to incorporate
      all information simultaneously and to provide valid and efficient inferences,
      thus allowing to produce a better insight into the biological mechanisms
      underlying the phenomenon under study. Accounting for the whole dynamics of the
      disease process is crucial in retrospective longitudinal studies. In this work,
      we present different approaches for modeling longitudinal and time-to-event data,
      retrieved from 648 HIV-infected patients enrolled in the Italian cohort of the
      CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) study,
      one of the largest AIDS collaborative cohort studies. In particular, we evaluate
      CD4 lymphocyte evolution over time (from the date of seroconversion) and overall
      survival, CD4 being one of the most important immunologic biomarker for HIV
      progression. Besides a standard separate modeling approach, we consider two
      alternative joint models: the traditional joint model and the joint latent class
      mixed model. Advantages and disadvantages of the different approaches are
      discussed. To compare the performances of these models, cross-validation
      procedures are also performed.

PMID- 24671659
TI  - Bayesian hierarchical modelling of noisy spatial rates on a modestly large and
      discontinuous irregular lattice.
AB  - We present Bayesian hierarchical spatial model development motivated from a
      recent analysis of noisy small area response rate data, named the Booster data.
      The Booster data are postcode-level aggregates from a recent mail-out recruitment
      for a physical exercise intervention in deprived urban neighbourhoods in
      Sheffield, UK. Bayesian hierarchical Bernoulli-binomial spatial mixture zero
      inflated Binomial models were developed for modelling overdispersion and for
      separation of systematic and random variations in the noisy and mostly low crude
      response rates. We present methods that enabled us to explore the underlying
      spatial rate variation, clustering of low or high response rate areas and
      neighbourhood characteristics that were associated with variations and patterns
      of invitation mail-outs, zero-response and response rates. Three spatial prior
      formulations, the intrinsic conditional autoregressive or (iCAR), the Besag-York
      Mollie (BYM) and the modified BYM models, were explored for their performance on
      modelling sparse data on a modestly large and discontinuous irregular lattice. An
      in-depth Bayesian analysis of the Booster data is presented, with the resulting
      posterior estimation and inference implemented via Markov chain Monte Carlo
      simulation in WinBUGS. With increasing availability of spatial data referenced at
      fine spatial scales such as the postcode, the sparse-data situation and the
      Bayesian models and methods discussed herein should have considerable relevance
      to small area disease and health mapping and to spatial regression.

PMID- 24671660
TI  - Introduction to the special issue on lymphangiogenesis in inflammation.

PMID- 24671661
TI  - True leukonychia in Crohn disease induced by selenium deficiency.

PMID- 24671662
TI  - Treatment of totally occluded aortic coarctation using a covered stent.

PMID- 24671663
TI  - Cor triatriatum dexter in a patient with pectus excavatum. A rare cause of right
      heart failure.

PMID- 24671664
TI  - Large arteriovenous malformation of the renal artery causing congestive heart
      failure.

PMID- 24671666
TI  - [Interventional hypertension therapy in diabetes mellitus. Effects on blood
      pressure and glucose metabolism?].
AB  - Hypertension is the most common chronic cardiovascular disease with increasing
      prevalence all over the world. Despite the availability of many effective
      antihypertensive drugs, blood pressure control to target values remains low. In
      the pathophysiology of therapy resistant hypertension, increased activity of the
      sympathetic nervous system with an imbalance between sympathetic and
      parasympathetic activity has been identified as a main contributor to the
      development and maintenance of hypertension. Catheter-based denervation of the
      renal sympathetic nerves has been described as reducing blood pressure and
      decreasing sympathetic activity in patients with resistant hypertension.
      Supplementary beneficial effects on common cardiovascular comorbidities, such as
      diabetes type 2, have been reported. The present review aims to give an overview
      about percutaneous renal denervation for treatment of hypertension and potential
      new therapeutic options to improve glycemic control. 

PMID- 24671667
TI  - Sexual and reproductive health and rights, HIV/AIDS, and public health.

PMID- 24671665
TI  - [Hypoglycemia and cardiac arrhythmia in patients with diabetes mellitus type 2].
AB  - Hypoglycemia is a common and potentially life-threatening adverse effect of
      inappropriate diabetes treatment. Typical cardiac complications are ischemia with
      angina pectoris, myocardial infarction, stroke and arrhythmias, such as atrial
      fibrillation (AF), ventricular tachycardia and heart failure. Elderly multimorbid
      patients with type 2 diabetes and polypharmacy and/or cardiac autonomous
      neuropathy represent a very high risk group for cardiovascular complications
      associated with hypoglycemia. Targets for glycemic control have to be adapted to
      the risk of hypoglycemia with a priority of stable glucose homeostasis without
      rapid fluctuations. Elderly patients with diabetes have a >20% risk of AF. At
      blood glucose levels of <3 mmol/l with a duration of >30 min, prolongation of QTc
      time and ventricular tachycardia occur with an increased risk of ventricular
      fibrillation and sudden death. Ventricular arrhythmias and AF significantly
      increase mortality in patients with heart failure. Rapid fluctuations with a mean
      amplitude of glucose excursion (MAGE) >5 mmol/l promote vulnerability of
      electrical stability of the heart, particularly in frail patients with
      preexisting coronary heart disease and autonomic neuropathy. Antihyperglycemic
      agents, such as metformin, acarbose and sodium glucose cotransporter 2 (SGLT2)
      inhibitors have only a low risk of severe hypoglycemia. Dipeptidyl peptase 4 (DPP
      IV) inhibitors and glucagon-like peptide 1 (GLP1) analogues as insulin
      secretagogues have a lower risk for hypoglycemia than sulfonylurea and insulin.
      Early basal insulin treatment in patients insufficiently controlled with
      metformin is efficient, safe and convenient. Targets for glucose control and
      HbA1c have to be individualized and the choice of drugs must be risk-adjusted.
      Risk of hypoglycemia should be used as guide in decision-making for safe
      treatment of diabetes. 

PMID- 24671668
TI  - Sulforaphane inhibits IL-1beta-induced proliferation of rheumatoid arthritis
      synovial fibroblasts and the production of MMPs, COX-2, and PGE2.
AB  - This study was performed to define the effects of sulforaphane on interleukin
      1beta (IL-1beta)-induced proliferation of rheumatoid arthritis synovial
      fibroblasts (RASFs), the expression of matrix metalloproteinases (MMPs) and
      cyclooxygenase (COX), and the production of prostaglandin E2 (PGE2) by RASFs. The
      proliferation of RASFs was evaluated with CCK-8 reagent in the presence of IL
      1beta with/without sulforaphane. The expression of MMPs, tissue inhibitor of
      metalloproteinase-1, COXs, intracellular mitogen-activated protein kinase
      signalings, including p-ERK, p-p38, p-JNK, and nuclear factor-kappaB (NF-kB), and
      the production of PGE2 were examined by Western blotting or semi-quantitative RT
      PCR and ELISA. Sulforaphane inhibits unstimulated and IL-1beta-induced
      proliferation of RASFs; the expression of MMP-1, MMP-3, and COX-2 mRNA and
      protein; and the PGE2 production induced by IL-1beta. Sulforaphane also inhibits
      the phosphorylation of ERK-1/2, p-38, and JNK and activation of NF-kB by IL
      1beta. These results indicate that sulforaphane inhibits the proliferation of
      synovial fibroblasts, the expression of MMPs and COX-2, and the production of
      PGE2, which are involved in synovitis and destruction of RA, and suggest that
      sulforaphane might be a new therapeutic agent for RA. 

PMID- 24671669
TI  - 2013 ACC/AHA cholesterol guideline for reducing cardiovascular risk: what is so
      controversial?
AB  - In November 2013, the American College of Cardiology and American Heart
      Association (ACC/AHA) released a clinical practice guideline on the treatment of
      blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) risk
      in adults. The guideline recommendations were developed from a rigorous
      systematic review of randomized, controlled trials (RCTs) and meta-analyses of
      RCTs that evaluated ASCVD outcomes. Major recommendations address a healthy
      lifestyle, identification of groups of patients most likely to experience a net
      benefit form statin therapy, appropriate intensity of statin therapy to reduce
      ASCVD, safety, decision-making in primary prevention, monitoring therapy, and
      appropriate use of nonstatin therapy. Areas of controversy are discussed. 

PMID- 24671670
TI  - Hemodiafiltration combined with resin-mediated absorption as a therapy for
      hyperlipidemic acute pancreatitis.
AB  - The aim of this study is to investigate whether hemodiafiltration combined with
      resin-mediated absorption is a better therapy for hyperlipidemic acute
      pancreatitis. Patients (n = 67) with acute pancreatitis treated in ICU from
      January 2009 to December 2012 were included in this study. Seven of these 67
      cases were diagnosed hyperlipidemic acute pancreatitis (HLAP). All the 7 HLAP
      patients went through fast, gastrointestinal decompression, anti-shock treatment,
      inhibition of pancreatic secretion, antiseptic treatments, and hemoperfusion (HP)
      combined with continuous veno venous hemodiafiltration (CVVHDF). After one round
      of treatment by resin adsorption, there was a significant decrease in serum
      triglycerides (TG) (29.78 %) and total cholesterol (TC) (24.02 %) levels (p <
      0.01). TG and TC levels dropped by 49.02 and 37.66 %, respectively, after 1-day
      treatment of HP + CVVHDF; by 62.81 and 47.37 % on day 2 post-treatment; and by
      69.57 and 49.47 % on day 3 post-treatment. All the 7 patients survived. The
      average time spent in the ICU was 7 +/- 3.8 days, and the average duration of
      hospitalization was 19 +/- 15.1 days. Our results show that hemoperfusion
      combined with hemodiafiltration is an efficient treatment as this approach can
      reduce plasma lipid levels effectively and reduce the risk of acute pancreatitis
      due to hyperlipidemia.

PMID- 24671671
TI  - Upstream and downstream processing of lovastatin by Aspergillus terreus.
AB  - The present study describes the enhanced production and purification of
      lovastatin by Aspergillus terreus in submerged batch fermentation. The
      enhancement of lovastatin production from A. terreus was attempted by random
      mutagenesis using ultraviolet radiations and nitrous acid. UV mutants exhibited
      increased efficiency for lovastatin production as compared with nitrous acid
      mutants. Among all the mutants developed, A. terreus UV-4 was found to be the
      hyper producer of lovastatin. This mutant gave 3.5-fold higher lovastatin
      production than the wild culture of A. terreus NRRL 265. Various cultural
      conditions were also optimized for hyper-producing mutant strain. 5 % glucose as
      carbon source, 1.5 % corn steep liquor as nitrogen source, initial pH value of 6,
      120 h of incubation period, and 28  degrees C of incubation temperature were
      found as best parameters for higher lovastatin production in shake flasks.
      Production of lovastatin by wild and mutant strains of A. terreus was also scaled
      up to laboratory scale fermentor. The fermentation process was conducted at 28 
      degrees C, 200 rpm agitation, and 1vvm air flow rate without pH control. After
      the optimization of cultural conditions in 250 ml Erlenmeyer flasks and scaling
      up to laboratory scale fermentor, the mutant A. terreus UV-4 gave eightfold
      higher lovastatin production (3249.95 MUg/ml) than its production by wild strain
      in shake flasks. Purification of lovastatin was carried out by solvent extraction
      method which yielded 977.1 mg/l of lovastatin with 98.99 % chromatographic purity
      and 26.76 % recovery. The crystal structure of lovastatin was determined using X
      ray diffraction analysis which is first ever reported.

PMID- 24671673
TI  - HSV-1 biology and life cycle.
AB  - Herpes simplex virus type 1 (HSV-1) is a common and important human pathogen that
      has been studied in a wide variety of contexts for several decades. This book
      presents chapters on protocols on many strands of HSV-1 research that are
      currently in use in leading laboratories. This chapter gives a brief overview of
      HSV-1 biology and life cycle, covering basic aspects of the virus and its
      replication in cultured cells, the diseases caused by the virus, viral latency,
      antiviral defenses, and the mechanisms that the virus uses to counteract these
      defenses. 

PMID- 24671672
TI  - The prediction of quality of life by physical, psychological and social
      components of frailty in community-dwelling older people.
AB  - PURPOSE: To assess the predictive validity of the 15 components of the Tilburg
      Frailty Indicator (TFI), a self-report questionnaire, for quality of life domains
      physical health, psychological, social relations and environmental in community
      dwelling older persons in a longitudinal study. METHODS: The predictive validity
      of the components of the TFI was tested in a sample of 484 community-dwelling
      persons aged 75 years and older in the Netherlands in 2008 (response rate 42%). A
      subset of all respondents participated two years later, in 2010 (n = 261, 54%),
      and a subset of these respondents participated again in 2012 (n = 196, 75%). The
      WHOQOL-BREF was used for measuring four quality of life domains. RESULTS: Four
      physical frailty components (physical unhealthy, difficulty in maintaining
      balance, difficulty in walking and physical tiredness), one psychological frailty
      component (feeling down) and one social frailty component (lack of social
      support) predicted future scores on quality of life domains, even after
      controlling for background characteristics and diseases. CONCLUSION: This
      longitudinal study showed that quality of life is predicted by physical as well
      as psychological and social frailty components. This finding emphasizes the
      relevance of a multidimensional assessment of frailty. To improve quality of life
      of older persons, special attention should go to the screening and subsequent
      interventions focusing on the frailty components difficulty in walking, feeling
      down and lack of social support.

PMID- 24671674
TI  - Herpes simplex virus growth, preparation, and assay.
AB  - In order to study the biology of herpes simplex virus or to use it as a vector in
      gene therapy, it is necessary to grow the virus and to prepare virus stocks. Many
      different protocols are available from different research groups working with
      herpes simplex virus type 1 or 2 (HSV-1 or HSV-2). This chapter describes the
      procedures used in our laboratory. 

PMID- 24671675
TI  - Isolation of herpes simplex virus nucleocapsid DNA.
AB  - As an inanimate virus, herpes simplex virus type 1 (HSV-1) necessarily encodes
      all of its functions in its DNA. Isolation of pure viral DNA allows multiple
      downstream applications, including the creation of recombinant HSV strains,
      cloning of selected regions, and sequencing of viral DNA. The term nucleocapsid
      refers to the combination of the viral genome with the enclosing capsid; these
      viral genomes are necessarily linear and have been packaged for egress, even if
      they are not yet released from the cell. In contrast, viral DNA that is not
      associated with capsids may include episomal or concatenated forms and may have
      modifications such as histones that are added within cells. During this protocol,
      the viral capsid protects the HSV genome from reagents that strip away and
      destroy most cellular contaminants. This procedure describes the isolation of
      viral nucleocapsids and their subsequent dissolution to purify clean, linear HSV
      DNA. 

PMID- 24671676
TI  - Construction and characterization of bacterial artificial chromosomes (BACs)
      containing herpes simplex virus full-length genomes.
AB  - Bacterial artificial chromosomes (BACs) are suitable vectors not only to maintain
      the large genomes of herpesviruses in Escherichia coli but also to enable the
      traceless introduction of any mutation using modern tools of bacterial genetics.
      To clone a herpes simplex virus genome, a BAC replication origin is first
      introduced into the viral genome by homologous recombination in eukaryotic host
      cells. As part of their nuclear replication cycle, genomes of herpesviruses
      circularize and these replication intermediates are then used to transform
      bacteria. After cloning, the integrity of the recombinant viral genomes is
      confirmed by restriction length polymorphism analysis and sequencing. The BACs
      may then be used to design virus mutants. Upon transfection into eukaryotic cells
      new herpesvirus strains harboring the desired mutations can be recovered and used
      for experiments in cultured cells as well as in animal infection models. 

PMID- 24671677
TI  - Engineering HSV-1 vectors for gene therapy.
AB  - Virus vectors have been employed as gene transfer vehicles for various
      preclinical and clinical gene therapy applications, and with the approval of
      Glybera (alipogene tiparvovec) as the first gene therapy product as a standard
      medical treatment (Yla-Herttuala, Mol Ther 20: 1831-1832, 2013), gene therapy has
      reached the status of being a part of standard patient care. Replication
      competent herpes simplex virus (HSV) vectors that replicate specifically in
      actively dividing tumor cells have been used in Phase I-III human trials in
      patients with glioblastoma multiforme, a fatal form of brain cancer, and in
      malignant melanoma. In fact, T-VEC (talimogene laherparepvec, formerly known as
      OncoVex GM-CSF) displayed efficacy in a recent Phase III trial when compared to
      standard GM-CSF treatment alone (Andtbacka et al. J Clin Oncol 31: sLBA9008,
      2013) and may soon become the second FDA-approved gene therapy product used in
      standard patient care. In addition to the replication-competent oncolytic HSV
      vectors like T-VEC, replication-defective HSV vectors have been employed in Phase
      I-II human trials and have been explored as delivery vehicles for disorders such
      as pain, neuropathy, and other neurodegenerative conditions. Research during the
      last decade on the development of HSV vectors has resulted in the engineering of
      recombinant vectors that are totally replication defective, nontoxic, and capable
      of long-term transgene expression in neurons. This chapter describes methods for
      the construction of recombinant genomic HSV vectors based on the HSV-1
      replication-defective vector backbones, steps in their purification, and their
      small-scale production for use in cell culture experiments as well as preclinical
      animal studies.

PMID- 24671678
TI  - Herpes simplex virus type 1 (HSV-1)-derived amplicon vectors.
AB  - Amplicons are defective, helper-dependent, herpes simplex virus type 1 (HSV-1)
      derived vectors. The main interest of these vectors as gene transfer tools stems
      from the fact that the amplicon vector genomes do not carry protein-encoding
      viral sequences. Consequently, they are completely safe for the host and nontoxic
      for the infected cells. Moreover, the complete absence of virus genes provides
      space to accommodate very large foreign DNA sequences, up to almost 150-kb, the
      size of the virus genome. This large transgene capacity can be used to deliver
      complete gene loci, including introns and exons, as well as long regulatory
      sequences, conferring tissue-specific expression or stable maintenance of the
      transgene in proliferating cells. During many years the development of these
      vectors and their application in gene transfer experiments was hindered by the
      presence of contaminating toxic helper virus particles in the vector stocks. In
      recent years, however, two different methodologies have been developed that allow
      generating amplicon stocks either completely free of helper particles or only
      faintly contaminated with fully defective helper particles. This chapter
      describes these two methodologies. 

PMID- 24671679
TI  - HSV-1 amplicon vectors as genetic vaccines.
AB  - HSV-1 amplicon vectors have been used as platforms for the generation of genetic
      vaccines against both DNA and RNA viruses. Mice vaccinated with such vectors
      encoding structural proteins from both foot-and-mouth disease virus and rotavirus
      were partially protected from challenge with wild-type virus (D'Antuono et al.
      Vaccine 28: 7363-7372, 2010; Laimbacher et al. Mol Ther 20: 1810-1820, 2012),
      indicating that HSV-1 amplicon vectors are attractive tools for the development
      of complex and safe genetic vaccines. This chapter describes the use of HSV-1
      amplicon vectors that encode individual or multiple viral structural proteins
      from a polycistronic transgene cassette in mammalian cells. More precisely,
      amplicon vectors that encode multiple structural viral proteins support the in
      situ production of viruslike particles (VLPs) in vector-infected cells. The
      expression of the viral genes is confirmed by Western blot and immune
      fluorescence analysis, and the generation of VLPs in vector-infected cells is
      demonstrated by electron microscopy. 

PMID- 24671680
TI  - Modification of HSV-1 to an oncolytic virus.
AB  - Cancer-permissive viruses or oncolytic viruses consist of either genetically
      engineered or naturally occurring strains that possess relatively selective
      replicative and/or infection abilities for cancer vs. normal cells (Chiocca, Nat
      Rev Cancer 2: 938-950, 2002). They can also be armed with additional anticancer
      cDNAs (e.g., cytokines, prodrug-activating, anti-angiogenesis genes, and others)
      to extend therapeutic effects (Kaur et al., Curr Gene Ther 9: 341-355, 2009).
      Herpes simplex virus type 1 (HSV-1) possesses several advantages as an oncolytic
      virus such as a rapid lytic cycle and a large capacity for insertion of
      heterologous DNA sequences (Wade-Martins et al., Nat Biotechnol, 19: 1067-1070,
      2001). However, the technical nuances of genetic manipulation of the HSV-1 genome
      may still be relatively challenging. Here, we describe a system that has been
      durable and consistent in providing the ability to generate multiple recombinant
      HSV-1. The HsvQuik technology utilizes an HSV-1 genome cloned in a bacterial
      artificial chromosome to recombine heterologous cDNAs in a relatively rapid and
      reliable manner (Terada et al., Gene Ther 13: 705-714, 2006).

PMID- 24671681
TI  - Herpes simplex virus mutant generation and dual-detection methods for gaining
      insight into latent/lytic cycles in vivo.
AB  - Two important components to a useful strategy to examine viral gene regulation in
      vivo are (1) a highly efficient protocol to generate viral mutants that limits
      undesired mutation and retains full replication competency in vivo and (2) an
      efficient system to detect and quantify viral promoter activity in rare cells in
      vivo. Our strategy and protocols for generating, characterizing, and employing
      HSV viral promoter/reporter mutants in vivo are provided in this two-part
      chapter. 

PMID- 24671682
TI  - Phenotypic and genotypic testing of HSV-1 resistance to antivirals.
AB  - Resistance testing of antivirals to herpes simplex virus type 1 can be done by
      phenotypic and genotypic methods. The determination of a resistant phenotype is
      based on the calculation of inhibitory concentrations for the antiviral drug,
      which should be tested. The main advantage is a clear interpretation of
      laboratory findings, but the method is time consuming and a considerable
      experience is required for handling infectious virus. Genotypic resistance
      testing is based on the detection of resistance-related mutations in viral genes
      encoding the thymidine kinase and DNA polymerase by means of amplification and
      sequencing. This approach has the advantage of being faster, but only frameshift
      mutations and stops of translation can be interpreted without doubt and numerous
      amino acid substitutions are diagnostically less conclusive. 

PMID- 24671683
TI  - Using homogeneous primary neuron cultures to study fundamental aspects of HSV-1
      latency and reactivation.
AB  - We describe a primary neuronal culture system suitable for molecular
      characterization of herpes simplex virus type 1 (HSV-1) infection, latency, and
      reactivation. While several alternative models are available, including
      infections of live animal and explanted ganglia, these are complicated by the
      presence of multiple cell types, including immune cells, and difficulties in
      manipulating the neuronal environment. The highly pure neuron culture system
      described here can be readily manipulated and is ideal for molecular studies that
      focus exclusively on the relationship between the virus and host neuron, the
      fundamental unit of latency. As such it allows for detailed investigations of
      both viral and neuronal factors involved in the establishment and maintenance of
      HSV-1 latency and in viral reactivation induced by defined stimuli. 

PMID- 24671684
TI  - Characterization of extracellular HSV-1 virions by proteomics.
AB  - The analysis of herpes simplex virus type 1 mature extracellular virions by
      proteomics requires highly enriched samples to limit false positives and favor
      the detection of true components. The protocol described below involves the
      removal of highly contaminating serum proteins and purification of the virions by
      a series of differential and density centrifugation steps. In addition, L
      particles, which are viral particles devoid of genome and capsid but present in
      the extracellular milieu, are depleted on Ficoll 400 gradients. As previously
      reported, the resulting viral particles are free of most contaminants and
      suitable for mass spectrometry. 

PMID- 24671685
TI  - A precipitation-based assay to analyze interactions of viral particles with
      cytosolic host factors.
AB  - Since viruses are obligate intracellular parasites, viral particles, subviral
      structures, and viral proteins enlist the support of host proteins to foster
      intracellular transport, viral gene expression, replication, and evasion from
      antiviral host responses. We have devised a biochemical in vitro method to
      analyze specific interactions of cytosolic factors with capsids of herpes simplex
      virus and to characterize host proteins that specifically coprecipitate with
      different types of viral particles by immunoblotting, mass spectrometry, and
      immunoelectron microscopy. Our method bridges the gap between assays such as co
      immunoprecipitation and yeast-two-hybrid approaches that determine direct binding
      between individual subunits of protein complexes and microscopy methods that
      analyze the dynamic interplay between intact viral particles and host factor
      complexes in intact cells. Our protocol can be extended to functional analyses of
      herpesvirus capsids and other viral structures with more complex host structures
      such as microtubule transport, genome uncoating at nuclear pores, or capsid
      envelopment at host membranes.

PMID- 24671686
TI  - Affinity purification combined with mass spectrometry to identify herpes simplex
      virus protein-protein interactions.
AB  - The identification and characterization of herpes simplex virus protein
      interaction complexes are fundamental to understanding the molecular mechanisms
      governing the replication and pathogenesis of the virus. Recent advances in
      affinity-based methods, mass spectrometry configurations, and bioinformatics
      tools have greatly increased the quantity and quality of protein-protein
      interaction datasets. In this chapter, detailed and reliable methods that can
      easily be implemented are presented for the identification of protein-protein
      interactions using cryogenic cell lysis, affinity purification, trypsin
      digestion, and mass spectrometry. 

PMID- 24671687
TI  - Preparation of herpes simplex virus-infected primary neurons for transmission
      electron microscopy.
AB  - Transmission electron microscopy (TEM) provides the resolution necessary to
      identify both viruses and subcellular components of cells infected with many
      types of viruses, including herpes simplex virus. Recognized as a powerful tool
      in both diagnostic and research-based virology laboratories, TEM has made
      possible the identification of new viruses and has contributed to the elucidation
      of virus life cycle and virus-host cell interaction. Whilst there are many sample
      preparation techniques for TEM, conventional processing using chemical fixation
      and resin embedding remains a useful technique, available in virtually all EM
      laboratories, for studying virus/cell ultrastructure. In this chapter, we
      describe the preparation of herpes simplex virus-infected primary neurons, grown
      on plastic cover slips, to allow sectioning of neurons and axons in their growth
      plane. This technique allows TEM examination of cell bodies, axons, growth cones,
      and varicosities, providing powerful insights into virus-cell interaction.

PMID- 24671688
TI  - Multifluorescence live analysis of herpes simplex virus type-1 replication.
AB  - The possibility to label specific viral and cellular structures with live cell
      markers such as autofluorescent proteins has greatly contributed to our
      understanding of diverse steps of the virus life cycle, as it allows monitoring
      virus replication in a spatial and temporal fashion. Here, we describe the multi
      fluorescent analysis of the multi-compartment herpes simplex virus type-1 by live
      cell confocal laser scanning microscopy. 

PMID- 24671689
TI  - Expression, purification, and crystallization of HSV-1 glycoproteins for
      structure determination.
AB  - HSV glycoproteins play important roles in the viral infectious cycle,
      particularly viral entry into the cell. Here we describe the protocol for
      expression, purification, and crystallization of viral glycoproteins based on
      those developed for the HSV-1 gB and HSV-2 gH/gL ectodomains. These protocols can
      be used for generating milligram amounts of wild-type (WT) or mutant gB and gH/gL
      ectodomains or can be adapted to produce purified ectodomains of other HSV
      glycoproteins for biochemical and structural studies. 

PMID- 24671690
TI  - Cryo-EM techniques to resolve the structure of HSV-1 capsid-associated
      components.
AB  - Electron cryo-microscopy has become a routine technique to determine the
      structure of biochemically purified herpes simplex virus capsid particles. This
      chapter describes the procedures of specimen preparation by cryopreservation; low
      dose and low temperature imaging in an electron cryo-microscope; and data
      processing for reconstruction. This methodology has yielded subnanometer
      resolution structures of the icosahedral capsid shell where alpha-helices and
      beta-sheets of individual subunits can be recognized. A relaxation of the
      symmetry in the reconstruction steps allows us to resolve the DNA packaging
      protein located at one of the 12 vertices in the capsid. 

PMID- 24671691
TI  - In vivo HSV-1 DNA transport studies using murine retinal ganglion cells.
AB  - The mammalian retina, brain, spinal cord, and peripheral ganglia are all
      heterogeneous tissues. Each is composed of neuronal and glial cell partners
      embedded in a connective tissue bed and supplied by vascular and immune cells.
      This complicated structure presents many challenges to neuroscientists and cell
      biologists, e.g., how to carry out a quantitative study of neurons in a mature
      animal surrounded by the hormonal and immune stimuli. A reductionist view leads
      investigators to study single neurons in vitro, subtracting the immune and
      vascular components and simplifying the problem. While this has advantages, it
      limits relevance of the study. We present a method for studying the axonal
      transport of Herpes simplex virus in mature neurons in situ. Using genetically
      identical mice and carefully controlling the delivery of virus, an investigator
      can obtain insight into the transport of virus to and from the neuron cell body
      within the cellular environment of an intact animal. 

PMID- 24671692
TI  - HSV-1 protein expression using recombinant baculoviruses.
AB  - The baculovirus expression system is an invaluable method for the expression of
      Herpes Simplex Virus 1 (HSV-1) proteins. The use of insect cells provides a
      eukaryotic system for the robust expression of heterologous proteins under
      control of the baculovirus polyhedrin gene promoter that naturally drives the
      high expression of the polyhedrin protein. Additionally, insect cells often
      initiate the necessary posttranslational modifications and/or disulfide-bond
      formation important for the proper folding of the protein. We and others have
      successfully expressed and purified several HSV-1 proteins including the
      polymerase, helicase-primase, single-strand DNA binding protein, and alkaline
      nuclease. The following protocol is based on 15 years of experience from our
      laboratory. 

PMID- 24671693
TI  - The murine intravaginal HSV-2 challenge model for investigation of DNA vaccines.
AB  - DNA vaccines have been licensed in veterinary medicine and have promise for
      humans. This format is relatively immunogenic in mice and guinea pigs, the two
      principle HSV-2 animal models, permitting rapid assessment of vectors, antigens,
      adjuvants, and delivery systems. Limitations include the relatively poor
      immunogenicity of naked DNA in humans and the profound differences in HSV-2
      pathogenesis between host species. Herein, we detail lessons learned over the
      last few years investigating candidate DNA vaccines in the progesterone-primed
      female mouse vaginal model of HSV-2 infection as a guide to investigators in the
      field. 

PMID- 24671694
TI  - Influence of metal-peptide complexation on fragmentation and inter-fragment
      hydrogen migration in electron transfer dissociation.
AB  - The use of metal salts in electrospray ionization (ESI) of peptides increases the
      charge state of peptide ions, facilitating electron transfer dissociation (ETD)
      in tandem mass spectrometry. In the present study, K(+) and Ca(2+) were used as
      charge carriers to form multiply-charged metal-peptide complexes. ETD of the
      potassium- or calcium-peptide complex was initiated by transfer of an electron to
      a proton remote from the metal cation, and a c'-z* fragment complex, in which the
      c' and z* fragments were linked together via a metal cation coordinating with
      several amino acid residues, was formed. The presence of a metal cation in the
      precursor for ETD increased the lifetime of the c'-z* fragment complex,
      eventually generating c* and z' fragments through inter-fragment hydrogen
      migration. The degree of hydrogen migration was dependent on the location of the
      metal cation in the metal-peptide complex, but was not reconciled with
      conformation of the precursor ion obtained by molecular mechanics simulation. In
      contrast, the location of the metal cation in the intermediate suggested by the
      ETD spectrum was in agreement with the conformation of "proton-removed"
      precursors, indicating that the charge reduction of precursor ions by ETD induces
      conformational rearrangement during the fragmentation process. 

PMID- 24671695
TI  - Absolute quantitation of glycosylation site occupancy using isotopically labeled
      standards and LC-MS.
AB  - N-linked glycans are required to maintain appropriate biological functions on
      proteins. Underglycosylation leads to many diseases in plants and animals;
      therefore, characterizing the extent of glycosylation on proteins is an important
      step in understanding, diagnosing, and treating diseases. To determine the
      glycosylation site occupancy, protein N-glycosidase F (PNGase F) is typically
      used to detach the glycan from the protein, during which the formerly
      glycosylated asparagine undergoes deamidation to become an aspartic acid. By
      comparing the abundance of the resulting peptide containing aspartic acid against
      the one containing non-glycosylated asparagine, the glycosylation site occupancy
      can be evaluated. However, this approach can give inaccurate results when
      spontaneous chemical deamidation of the non-glycosylated asparagine occurs. To
      overcome this limitation, we developed a new method to measure the glycosylation
      site occupancy that does not rely on converting glycosylated peptides to their
      deglycosylated forms. Specifically, the overall protein concentration and the non
      glycosylated portion of the protein are quantified simultaneously by using heavy
      isotope-labeled internal standards coupled with LC-MS analysis, and the extent of
      site occupancy is accurately determined. The efficacy of the method was
      demonstrated by quantifying the occupancy of a glycosylation site on bovine
      fetuin. The developed method is the first work that measures the glycosylation
      site occupancy without using PNGase F, and it can be done in parallel with
      glycopeptide analysis because the glycan remains intact throughout the workflow. 

PMID- 24671696
TI  - Oxidation of methionine residues in polypeptide ions via gas-phase ion/ion
      chemistry.
AB  - The gas-phase oxidation of methionine residues is demonstrated here using ion/ion
      reactions with periodate anions. Periodate anions are observed to attach in
      varying degrees to all polypeptide ions irrespective of amino acid composition.
      Direct proton transfer yielding a charge-reduced peptide ion is also observed. In
      the case of methionine and, to a much lesser degree, tryptophan-containing
      peptide ions, collisional activation of the complex ion generated by periodate
      attachment yields an oxidized peptide product (i.e., [M + H + O](+)), in addition
      to periodic acid detachment. Detachment of periodic acid takes place exclusively
      for peptides that do not contain either a methionine or tryptophan side chain. In
      the case of methionine-containing peptides, the [M + H + O](+) product is
      observed at a much greater abundance than the proton transfer product (viz., [M +
      H](+)). Collisional activation of oxidized Met-containing peptides yields a
      signature loss of 64 Da from the precursor and/or product ions. This unique loss
      corresponds to the ejection of methanesulfenic acid from the oxidized methionine
      side chain and is commonly used in solution-phase proteomics studies to determine
      the presence of oxidized methionine residues. The present work shows that
      periodate anions can be used to 'label' methionine residues in polypeptides in
      the gas phase. The selectivity of the periodate anion for the methionine side
      chain suggests several applications including identification and location of
      methionine residues in sequencing applications. 

PMID- 24671697
TI  - Identifying high-risk medication: a systematic literature review.
AB  - PURPOSE: A medication error (ME) is an error that causes damage or poses a threat
      of harm to a patient. Several studies have shown that only a minority of MEs
      actually causes harm, and this might explain why medication reviews at hospital
      admission reduce the number of MEs without showing an effect on length of
      hospital stay, readmissions, or death. The purpose of this study was to define
      drugs that actually cause serious MEs. We conducted a literature search of
      medication reviews and other preventive efforts. METHODS: A systematic search in
      PubMed, Embase, Cochrane Reviews, Psycinfo, and SweMed+ was performed. Danish
      databases containing published patient complaints, patient compensation, and
      reported medication errors were also searched. Articles and case reports were
      included if they contained information of an ME causing a serious adverse
      reaction (AR) in a patient. Information concerning AR seriousness, causality, and
      preventability was required for inclusion. RESULTS: This systematic literature
      review revealed that 47 % of all serious MEs were caused by seven drugs or drug
      classes: methotrexate, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDS),
      digoxin, opioids, acetylic salicylic acid, and beta-blockers; 30 drugs or drug
      classes caused 82 % of all serious MEs. The top ten drugs involved in fatal
      events accounted for 73 % of all drugs identified. CONCLUSION: Increasing focus
      on seven drugs/drug classes can potentially reduce hospitalizations, extended
      hospitalizations, disability, life-threatening conditions, and death by almost 50
      %.

PMID- 24671699
TI  - Clinician-dependent variations in inappropriate use of myocardial perfusion
      imaging: training, specialty, and location.
AB  - BACKGROUND: Inappropriate use of myocardial perfusion imaging (MPI) may vary
      depending on the training, specialty, or practice location of the clinician.
      METHODS: We conducted a cross-sectional investigation of consecutive patients who
      underwent MPI at our Veterans Affairs medical center between December 2010 and
      July 2011. Characteristics of the MPI ordering clinicians were extracted to
      investigate any associations with inappropriate use. RESULTS: 582 patients were
      included, 9.8% were inappropriate. No difference in inappropriate use was
      observed between cardiology and non-cardiology clinicians (n = 21, 9.5% vs n =
      36, 10.0%, P = .83); no difference was noted between nurse
      practitioners/physician assistants, attending physicians, and housestaff (7.5% vs
      11.2% vs 1.8%, P = .06). Comparing inpatient, emergency department and outpatient
      clinician groups, the difference was null (8.6% vs 6.3% vs 10.1%, P = .75). For
      most clinician groups, the most common inappropriate indication was an
      asymptomatic scenario; however, some groups were different: definite acute
      coronary syndrome for inpatient clinicians and low risk syncope for emergency
      medicine clinicians. CONCLUSIONS: Clinician groups appear to order inappropriate
      MPI at similar rates, regardless of their training, specialty, or practice
      location. Differences in the most common type of inappropriate testing suggest
      that interventions to reduce inappropriate use should be tailored to specific
      clinician types.

PMID- 24671700
TI  - Fibrin clot properties and their modulation in thrombotic disorders.
AB  - Accumulating evidence indicates that accelerated formation of fibrin clots
      composed of compact, highly-branched networks with thin fibres which are
      relatively resistant to plasmin-mediated lysis can be commonly observed in
      patients with venous or arterial thrombosis. This review discusses
      characteristics of fibrin clot structure and function in patients with various
      thromboembolic manifestations, in particular myocardial infarction, ischaemic
      stroke and venous thromboembolism, based on the publications till December 2013.
      Moreover, factors will be presented that in vivo unfavourably determine altered
      fibrin clot properties in thrombotic disorders and modalities that can improve
      clot phenotype. 

PMID- 24671698
TI  - Physiological underpinnings associated with differences in pace of life and
      metabolic rate in north temperate and neotropical birds.
AB  - Animal life-history traits fall within limited ecological space with animals that
      have high reproductive rates having short lives, a continuum referred to as a
      "slow-fast" life-history axis. Animals of the same body mass at the slow end of
      the life-history continuum are characterized by low annual reproductive output
      and low mortality rate, such as is found in many tropical birds, whereas at the
      fast end, rates of reproduction and mortality are high, as in temperate birds.
      These differences in life-history traits are thought to result from trade-offs
      between investment in reproduction or self-maintenance as mediated by the biotic
      and abiotic environment. Thus, tropical and temperate birds provide a unique
      system to examine physiological consequences of life-history trade-offs at
      opposing ends of the "pace of life" spectrum. We have explored the implications
      of these trade-offs at several levels of physiological organization including
      whole-animal, organ systems, and cells. Tropical birds tend to have higher
      survival, slower growth, lower rates of whole-animal basal metabolic rate and
      peak metabolic rate, and smaller metabolically active organs compared with
      temperate birds. At the cellular level, primary dermal fibroblasts from tropical
      birds tend to have lower cellular metabolic rates and appear to be more resistant
      to oxidative cell stress than those of temperate birds. However, at the
      subcellular level, lipid peroxidation rates, a measure of the ability of lipid
      molecules within the cell membranes to thwart the propagation of oxidative
      damage, appear not to be different between tropical and temperate species.
      Nevertheless, lipids in mitochondrial membranes of tropical birds tend to have
      increased concentrations of plasmalogens (phospholipids with antioxidant
      properties), and decreased concentrations of cardiolipin (a complex phospholipid
      in the electron transport chain) compared with temperate birds. 

PMID- 24671701
TI  - Acute generalized exanthematous pustulosis induced by sorafenib.

PMID- 24671702
TI  - Electrophysiological aberrations associated with negative symptoms in
      schizophrenia.
AB  - Clinical heterogeneity is a confound common to all of schizophrenia research.
      Deficit schizophrenia has been proposed as a homogeneous disease entity within
      the schizophrenia syndrome. The use of the Schedule for the Deficit Syndrome
      (SDS) has allowed the definition of a subgroup dominated by persistent and
      primary negative symptoms. While a number of studies have appeared over the years
      examining the electrophysiological correlates of the cluster of negative symptoms
      in schizophrenia, only a few studies have actually focused on the Deficit
      Syndrome (DS). In this chapter, electrophysiological investigations utilizing
      EEG, Evoked Potentials (EPs), polysomnography (PSG), or magnetoencephalography
      (MEG) to probe "negative symptoms," or "Deficit Syndrome" are reviewed. While
      this line of research is evidently in its infancy, two significant trends emerge.
      First, spectral EEG studies link increased slow wave activity during wakefulness
      to the prevalence of negative symptoms. Second, sleep studies point to an
      association between decrease in slow wave sleep and prevalence of negative
      symptoms. Several studies also indicate a relationship of negative symptoms with
      reduced alpha activity. A host of other abnormalities including sensory gating
      and P300 attenuation are less consistently reported. Three studies specifically
      addressed electrophysiology of the DS. Two of the three studies provided evidence
      suggesting that the DS may be a separate disease entity and not simply a severe
      form of schizophrenia. 

PMID- 24671703
TI  - Sleep and synaptic plasticity in the developing and adult brain.
AB  - Sleep is hypothesized to play an integral role in brain plasticity. This has
      traditionally been investigated using behavioral assays. In the last 10-15 years,
      studies combining sleep measurements with in vitro and in vivo models of synaptic
      plasticity have provided exciting new insights into how sleep alters synaptic
      strength. In addition, new theories have been proposed that integrate older ideas
      about sleep function and recent discoveries in the field of synaptic plasticity.
      There remain, however, important challenges and unanswered questions. For
      example, sleep does not appear to have a single effect on synaptic strength. An
      unbiased review of the literature indicates that the effects of sleep vary widely
      depending on ontogenetic stage, the type of waking experience (or stimulation
      protocols) that precede sleep and the type of neuronal synapse under examination.
      In this review, I discuss these key findings in the context of current theories
      that posit different roles for sleep in synaptic plasticity. 

PMID- 24671704
TI  - [Granulomatous mycosis fungoides: combination therapy with bexarotene and PUVA].
AB  - A 74-year-old male with granulomatous mycosis fungoides presented with multiple,
      red-brown macules and plaques up to 8 cm in diameter, just as in classical
      mycosis fungoides. Dermatohistopathologic findings showed extensive granulomatous
      infiltrates, in which clonality could be detected in various locations via T cell
      receptor rearrangement. Granulomatous mycosis fungoides is a very rare form of
      mycosis fungoides with histological resemblance to granulomatous slack skin. It
      shows a rather aggressive course and can be challenging to diagnose. In our case,
      combination treatment with bexarotene and bath PUVA, as recommended in
      guidelines, resulted in an impressive improvement of the skin lesions within ten
      weeks.

PMID- 24671705
TI  - Payment mechanism and GP self-selection: capitation versus fee for service.
AB  - This paper analyzes the consequences of allowing gatekeeping general
      practitioners (GPs) to select their payment mechanism. We model GPs' behavior
      under the most common payment schemes (capitation and fee for service) and when
      GPs can select one among them. Our analysis considers GP heterogeneity in terms
      of both ability and concern for their patients' health. We show that when the
      costs of wasteful referrals to costly specialized care are relatively high, fee
      for service payments are optimal to maximize the expected patients' health net of
      treatment costs. Conversely, when the losses associated with failed referrals of
      severely ill patients are relatively high, we show that either GPs' self
      selection of a payment form or capitation is optimal. Last, we extend our
      analysis to endogenous effort and to competition among GPs. In both cases, we
      show that self-selection is never optimal. 

PMID- 24671706
TI  - A satellite cell-specific knockout of the androgen receptor reveals myostatin as
      a direct androgen target in skeletal muscle.
AB  - Androgens have well-established anabolic actions on skeletal muscle, although the
      direct effects of the androgen receptor (AR) in muscle remain unclear. We
      generated satellite cell-specific AR-knockout (satARKO) mice in which the AR is
      selectively ablated in satellite cells, the muscle precursor cells. Total-limb
      maximal grip strength is decreased by 7% in satARKO mice, with soleus muscles
      containing ~10% more type I fibers and 10% less type IIa fibers than the
      corresponding control littermates. The weight of the perineal levator ani muscle
      is markedly reduced (-52%). Thus, muscle AR is involved in fiber-type
      distribution and force production of the limb muscles, while it is a major
      determinant of the perineal muscle mass. Surprisingly, myostatin (Mstn), a strong
      inhibitor of skeletal muscle growth, is one of the most androgen-responsive genes
      (6-fold reduction in satARKO) through direct transcription activation by the AR.
      Consequently, muscle hypertrophy in response to androgens is augmented in Mstn
      knockout mice. Our finding that androgens induce Mstn signaling to restrain their
      own anabolic actions has implications for the treatment of muscle wasting
      disorders.-Dubois, V., Laurent, M. R., Sinnesael, M., Cielen, N., Helsen, C.,
      Clinckemalie, L., Spans, L., Gayan-Ramirez, G., Deldicque, L., Hespel, P.,
      Carmeliet, G., Vanderschueren, D., and Claessens, F. A satellite cell-specific
      knockout of the androgen receptor reveals myostatin as a direct androgen target
      in skeletal muscle. 

PMID- 24671707
TI  - Deimination of linker histones links neutrophil extracellular trap release with
      autoantibodies in systemic autoimmunity.
AB  - Autoantibodies to nuclear antigens arise in human autoimmune diseases, but a
      unifying pathogenetic mechanism remains elusive. Recently we reported that
      exposure of neutrophils to inflammatory conditions induces the citrullination of
      core histones by peptidylarginine deiminase 4 (PAD4) and that patients with
      autoimmune disorders produce autoantibodies that recognize such citrullinated
      histones. Here we identify histone H1 as an additional substrate of PAD4,
      localize H1 within neutrophil extracellular traps, and detect autoantibodies to
      citrullinated H1 in 6% of sera from patients with systemic lupus erythematosus
      and Sjogren's syndrome. No preference for deiminated H1 was observed in healthy
      control sera and sera from patients with scleroderma or rheumatoid arthritis. We
      map binding to the winged helix of H1 and determine that citrulline 53 represents
      a key determinant of the autoantibody epitope. In addition, we quantitate RNA for
      H1 histone subtypes in mature human neutrophils and identify citrulline residues
      by liquid chromatography and tandem mass spectrometry. Our results indicate that
      deimination of linker histones generates new autoantibody epitopes with enhanced
      potential for stimulating autoreactive human B cells.-Dwivedi, N., Neeli, I.,
      Schall, N., Wan, H., Desiderio, D. M., Csernok, E., Thompson, P. R., Dali, H.,
      Briand, J.-P., Muller, S., Radic, M. Deimination of linker histones links
      neutrophil extracellular trap release with autoantibodies in systemic
      autoimmunity. 

PMID- 24671710
TI  - Memories of David Denison.

PMID- 24671708
TI  - Inhibition of Janus kinase signaling during controlled mechanical ventilation
      prevents ventilation-induced diaphragm dysfunction.
AB  - Controlled mechanical ventilation (CMV) is associated with the development of
      diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is
      thought to contribute significantly to delayed weaning of patients. Therefore,
      therapeutic strategies for preventing these processes may have clinical benefit.
      The aim of the current study was to investigate the role of the Janus kinase
      (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling
      pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced
      diaphragm atrophy and contractile dysfunction coincided with marked increases in
      STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727).
      STAT3 activation was accompanied by its translocation into mitochondria within
      diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling
      during CMV prevented phosphorylation of both target sites on STAT3, eliminated
      the accumulation of phosphorylated STAT3 within the mitochondria, and reversed
      the pathologic alterations in mitochondrial function, reduced oxidative stress in
      the diaphragm, and maintained normal diaphragm contractility. In addition, JAK
      inhibition during CMV blunted the activation of key proteolytic pathways in the
      diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3
      signaling in the development of diaphragm muscle atrophy and dysfunction during
      CMV and suggest that the delayed extubation times associated with CMV can be
      prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L.,
      Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S.,
      Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D.,
      Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C.,
      Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder,
      A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S.,
      Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus
      kinase signaling during controlled mechanical ventilation prevents ventilation
      induced diaphragm dysfunction. 

PMID- 24671709
TI  - Identification of new genetic polymorphisms that alter the dietary requirement
      for choline and vary in their distribution across ethnic and racial groups.
AB  - Effect alleles (alleles with a polymorphism that is associated with the effect
      being measured) in a small number of single-nucleotide polymorphisms (SNPs) are
      known to influence the dietary requirement for choline. In this study, we
      examined a much larger number of SNPs (n=200) in 10 genes related to choline
      metabolism for associations with development of organ dysfunction (liver or
      muscle) when 79 humans were fed a low-choline diet. We confirmed that effect
      alleles in SNPs such as the C allele of PEMT rs12325817 increase the risk of
      developing organ dysfunction in women when they consume a diet low in choline,
      and we identified novel effect alleles, such as the C allele of CHKA SNP
      rs7928739, that alter dietary choline requirements. When fed a low-choline diet,
      some people presented with muscle damage rather than liver damage; several effect
      alleles in SLC44A1 (rs7873937, G allele; rs2771040, G; rs6479313, G; rs16924529,
      A; and rs3199966, C) and one in CHKB (rs1557502, A) were more common in these
      individuals. This suggests that pathways related to choline metabolism are more
      important for normal muscle function than previously thought. In European,
      Mexican, and Asian Americans, and in individuals of African descent, we examined
      the prevalence of the effect alleles in SNPs that alter choline requirement and
      found that they are differentially distributed among people of different ethnic
      and racial backgrounds. Overall, our study has identified novel genetic variants
      that modulate choline requirements and suggests that the dietary requirement for
      choline may be different across racial and ethnic groups.-Da Costa, K.-A.,
      Corbin, K. D., Niculescu, M. D., Galanko, J. A., Zeisel, S. H. Identification of
      new genetic polymorphisms that alter the dietary requirement for choline and vary
      in their distribution across ethnic and racial groups. 

PMID- 24671711
TI  - A new instrument to assess physician skill at chest tube insertion: the TUBE
      iCOMPT.
AB  - Currently no tool exists to assess proceduralist skill at chest tube insertion.
      As inadequate doctor procedural competence has repeatedly been associated with
      adverse events, there is a need for a tool to assess procedural competence. This
      study aims to develop and examine the validity of a tool to assess competency at
      insertion of a chest tube, using either the Seldinger technique or blunt
      dissection. A 5-domain 100-point assessment tool was developed inline with
      British Thoracic Society guidelines and international consensus-the Chest Tube
      Insertion Competency Test (TUBE-iCOMPT). The instrument was used to assess chest
      tube insertion in mannequins and live patients. 29 participants (9 novices, 14
      intermediate and 6 advanced) were tested by 2 blinded expert examiners on 2
      occasions. The tool's validity was examined by demonstrating: (1) stratification
      of participants according to expected level of expertise (analysis of variance),
      and (2) test-retest and intertester reliability (intraclass correlation
      coefficient). The intraclass correlation coefficient of repeated scores for the
      Seldinger technique and blunt dissection, were 0.92 and 0.91, respectively, for
      test-retest results, and 0.98 and 0.95, respectively, for intertester results.
      Clear stratification of scores according to participant experience was seen
      (p<0.0001). There was no significant difference between scores obtained using
      mannequins or live patients. This study has validated the TUBE-iCOMPT, which
      could now be incorporated into chest tube insertion training programmes,
      providing a way to document acquisition of skill, guide individualised teaching,
      and assist with the assessment of the adequacy of clinician training.

PMID- 24671712
TI  - Engineering pre-SUMO4 as efficient substrate of SENP2.
AB  - SUMOylation, one of the most important protein post-translational modifications,
      plays critical roles in a variety of physiological and pathological processes.
      SENP (Sentrin/SUMO-specific protease), a family of SUMO-specific proteases, is
      responsible for the processing of pre-SUMO and removal of SUMO from conjugated
      substrates. SUMO4, the latest discovered member in the SUMO family, has been
      found as a type 1 diabetes susceptibility gene and its maturation is not
      understood so far. Despite the 14 amino acid differences between pre-SUMO4 and
      SUMO2, pre-SUMO4 is not processed by SENP2 but pre-SUMO2 does. A novel
      interdisciplinary approach involving computational modeling and a FRET-based
      protease assay was taken to engineer pre-SUMO4 as a substrate of SENP2. Given the
      difference in net charge between pre-SUMO4 and pre-SUMO2, the computational
      framework analysis of electrostatic similarities of proteins was applied to
      determine the contribution of each ionizable amino acid in a model of SENP2-(pre
      SUMO4) binding, and to propose pre-SUMO4 mutations. The specificities of the
      SENP2 toward different pre-SUMO4 mutants were determined using a quantitative
      FRET assay by characterizing the catalytic efficiencies (kcat/KM). A single amino
      acid mutation made pre-SUMO4 amenable to SENP2 processing and a combination of
      two amino acid mutations made it highly accessible as SENP2 substrate. The
      combination of the two approaches provides a powerful protein engineering tool
      for future SUMOylation studies. 

PMID- 24671713
TI  - Retention of tooth-colored restorations in non-carious cervical lesions--a
      systematic review.
AB  - OBJECTIVES: The aim of this review was to assess the effect of different adhesive
      systems and tooth preparation on the retention of tooth-colored restorative
      materials placed in non-carious cervical lesions (NCCLs). METHODS: Randomized
      clinical trials with a minimum of 3 years of follow-up that evaluated the
      effectiveness of tooth-colored materials, adhesive systems, and preparation
      techniques for the restoration of NCCLs were selected. The Cochrane Central
      Register of Controlled Trials (CENTRAL), EMBASE (OVID), the Latin American and
      Caribbean Health Sciences Literature database (LILACS), and Medline (OVID)
      electronic databases were searched from 1990 to 2013. RESULTS: Twenty-seven
      randomized clinical trials were included and reviewed. Meta-analysis was used to
      determine the relative risk of loss of tooth-colored NCCL restorations between
      different categories of adhesive systems. The effect of tooth preparation could
      not be similarly analyzed. CONCLUSION: The current best evidence indicates that a
      glass ionomer cement has a significantly lower risk of loss of a NCCL restoration
      compared to either a three-step etch-and-rinse or a two-step etch-and-rinse
      adhesive system; a three-step etch-and-rinse adhesive system has a significantly
      lower risk of loss of a NCCL restoration compared to a two-step etch-and-rinse
      adhesive system. No significant difference could be observed in the risk of loss
      of a tooth-colored NCCL restoration between a three-step etch-and-rinse adhesive
      system and either a two-step self-etch or a one-step self-etch adhesive system.

PMID- 24671714
TI  - Effect of theobromine-containing toothpaste on dentin tubule occlusion in situ.
AB  - OBJECTIVES: Dentin hypersensitivity (DH) is treated by either occlusion of dentin
      tubules or nerve desensitization. This in situ study compared dentin tubules
      occlusion by theobromine-containing dentifrices with (Theodent-classic-F(r), TCF)
      and without (Theodent-classic(r), TC) fluoride with 1,500 ppm fluoride
      toothpaste, Colgate(r)-Regular (Fluoride) and Novamin(r)-containing toothpaste,
      Sensodyne(r)-5000-Nupro (Novamin(r)). METHODS: Each subject wore four intraoral
      appliances bearing dentin blocks while using one of four test dentifrices (n =
      20/dentifrice) twice daily for 7 days. The four appliances were removed
      successively after 1, 2, 3, and 7 days. Treated blocks and their control
      (untreated) blocks were examined with scanning electron microscopy (SEM). Effects
      were compared statistically (ANOVA/Tukey's) based on percentage of surface area
      covered by deposited precipitate layer (%DPL) and percentage of fully open
      (%FOT), partially occluded (%POT), and completely occluded (%COT) tubules in each
      block calculated relative to the number of tubules in their control blocks.
      RESULTS: SEM observation indicated an increased %COT and %DPL over time. After 1
      and 2 days, %COT was comparable with TC and TCF, and significantly (p < 0.05)
      higher compared with Novamin(r) and Fluoride. Following 3 and 7 days, %COT was
      comparable among TC, TCF, and Novamin(r), but remained significantly lower in
      Fluoride. At any time, %DPL was significantly (p < 0.05) higher in TC, TCF, and
      Novamin(r) compared with Fluoride. CONCLUSIONS: Theobromine-containing
      toothpastes with and without fluoride have equal potential in occluding dentin
      tubules within a shorter time period than Novamin(r)-containing toothpaste;
      however, the three demonstrated equal potential after 1 week, but not the
      fluoride toothpaste. CLINICAL RELEVANCE: Theobromine-containing toothpaste
      promoted dentin tubule occlusion thus shows potential to relief DH.

PMID- 24671715
TI  - Impact of genital warts on emotional and sexual well-being differs by gender.
AB  - To assess gender-specific impact of genital warts on health-related quality of
      life (HRQoL), and to explore to what extent sexual characteristics and clinical
      symptoms influenced the impact on emotional and sexual well-being of both sexes.
      We conducted a survey of sexual and clinical characteristics from persons
      diagnosed with genital warts at STI clinics. HRQoL was measured using two
      measurement tools: 1) the generic EQ-5D; and 2) the genital warts-specific CECA
      10 including an emotional well-being and a sexual activity dimension. The EQ-5D
      scores were compared with scores of the general population. Descriptive analyses
      were used to explore characteristics associated with HRQoL scores stratified for
      gender. The HRQoL-measurement tools showed that genital warts have especially an
      emotional impact. The impact of genital warts on HRQoL was greater for women than
      for men. In addition, the CECA-10 showed that in women the impact of genital
      warts on sexual activity was influenced by age, relationship status and number of
      warts. No related factors were seen in men. Genital warts have a greater impact
      on women than on men. In women, sexual and clinical factors influenced the impact
      of genital warts on well-being, whereas in men no such factors were found. 

PMID- 24671716
TI  - Estimating HIV incidence in eastern European country of Georgia: 2010-2012.
AB  - The knowledge of HIV incidence is essential to better understand patterns of HIV
      transmission. We estimated HIV incidence over 2010-2012 in the eastern European
      country of Georgia. Mathematical modeling using Spectrum software and assay-based
      recent infection testing algorithm were applied. The study included 1155 HIV
      patients newly diagnosed in 2010-2012 (84% of total diagnoses). Of them, 231 were
      determined to be recently infected on the recent infection testing algorithm. The
      proportion of recent cases did not differ between 2010, 2011 and 2012 (20.4% vs.
      19.4% vs. 20.2%, p = 0.94). Both study methods derived comparable estimates
      ranging from 0.2 to 0.3%, which is up to twice as high as rates of new diagnosis
      reported in the same period. Despite the relatively stable HIV incidence over
      2010-2012, the epidemic continues to grow because of the increasing gap between
      HIV-infected and diagnosed persons. Increased efforts are needed to reduce the
      number of people with undiagnosed HIV.

PMID- 24671717
TI  - Pentosan polysulfate treatment ameliorates motor function with increased serum
      soluble vascular cell adhesion molecule-1 in HTLV-1-associated neurologic
      disease.
AB  - The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by
      lower extremity motor dysfunction is immunomodulatory treatment, with drugs such
      as corticosteroid hormone and interferon-alpha, at present. However, there are
      many issues in long-term treatment with these drugs, such as insufficient effects
      and various side effects. We now urgently need to develop other therapeutic
      strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely
      used in Europe for the past 50 years as a thrombosis prophylaxis and for the
      treatment of phlebitis. We conducted a clinical trial to test the effect of
      subcutaneous administration of PPS in 12 patients with HAM/TSP in an open-labeled
      design. There was a marked improvement in lower extremity motor function, based
      on reduced spasticity, such as a reduced time required for walking 10 m and
      descending a flight of stairs. There were no significant changes in HTLV-I
      proviral copy numbers in peripheral blood contrary to the inhibitory effect of
      PPS in vitro for intercellular spread of HTLV-I. However, serum soluble vascular
      cell adhesion molecule (sVCAM)-1 was significantly increased without significant
      changes of serum level of chemokines (CXCL10 and CCL2). There was a positive
      correlation between increased sVCAM-1and reduced time required for walking 10 m.
      PPS might induce neurological improvement by inhibition of chronic inflammation
      in the spinal cord, through blocking the adhesion cascade by increasing serum
      sVCAM-1, in addition to rheological improvement of the microcirculation. PPS has
      the potential to be a new therapeutic tool for HAM/TSP.

PMID- 24671719
TI  - Prevalence of human Herpesviridae in cerebrospinal fluid of patients with
      multiple sclerosis and noninfectious neurological disease in the Netherlands.
AB  - Prevalence of eight human herpesviruses (HHV1-8) was determined by real-time PCR
      in cell-rich cerebrospinal fluid (CSF) samples, obtained early after disease
      symptoms, of Dutch patients with multiple sclerosis (MS) and other noninfectious
      central nervous system diseases (NIND). Whereas HHV1-8 DNA was undetectable in
      CSF samples of MS patients, HHV6 DNA was detected in a plexus neuritis case and
      HHV7 DNA in an ependymoma and a Behcets' disease patient. However, intrathecal
      HHV infection was not detected. Data indicate that HHV1-8 are rarely detected in
      CSF of Dutch NIND patients and do not support the role of intrathecal HHV
      infection early after onset of disease symptoms in MS.

PMID- 24671718
TI  - Hepatitis C virus (HCV) interaction with astrocytes: nonproductive infection and
      induction of IL-18.
AB  - Hepatitis C virus (HCV) infection causes the central nervous system (CNS)
      abnormalities in more than 50 % of chronically infected subjects. However, the
      underlying mechanisms are largely unknown. In this study, we characterized the
      HCV interactions with astrocytes, one of the putative HCV target cells in the
      brain. We demonstrated that primary human astrocytes (PHA) were very
      inefficiently infected by HCV, either in the cell-free form or through cell-cell
      contact. We then determined the potential restriction steps of HCV infection and
      replication in these cells. PHA expressed all known HCV receptors but failed to
      support HCV entry. HCV IRES-mediated RNA translation was functional in PHA and
      further enhanced by miR122 expression. Nevertheless, PHA did not support HCV
      replication regardless of miR122 expression. To our great surprise, we found that
      HCV exposure induced robust IL-18 expression in PHA and exhibited direct
      neurotoxicity. Taken together, these results showed that astrocytes did not
      support productive HCV infection and replication, but HCV interactions with
      astrocytes and neurons alone might be sufficient to cause CNS dysfunction. 

PMID- 24671720
TI  - Effect of thyroxine on brain microstructure in extremely premature babies:
      magnetic resonance imaging findings in the TIPIT study.
AB  - BACKGROUND: In order to assess relationships between thyroid hormone status and
      findings on brain MRI, a subset of babies was recruited to a multi-centre
      randomised, placebo-controlled trial of levothyroxine (LT4) supplementation for
      babies born before 28 weeks' gestation (known as the TIPIT study, for Thyroxine
      supplementation In Preterm InfanTs). These infants were imaged at term
      equivalence. MATERIALS AND METHODS: Forty-five TIPIT participants had brain MRI
      using diffusion tensor imaging (DTI) to estimate white matter development by
      apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography
      metrics of number and length of streamlines. We made comparisons between babies
      with the lowest and highest plasma FT4 concentrations during the initial 4 weeks
      after birth. RESULTS: There were no differences in DTI metrics between babies who
      had received LT4 supplementation and those who had received a placebo. Among
      recipients of a placebo, babies in the lowest quartile of plasma-free thyroxine
      (FT4) concentrations had significantly higher apparent diffusion coefficient
      measurements in the posterior corpus callosum and streamlines that were shorter
      and less numerous in the right internal capsule. Among LT4-supplemented babies,
      those who had plasma FT4 concentrations in the highest quartile had significantly
      lower apparent diffusion coefficient values in the left occipital lobe, higher
      fractional anisotropy in the anterior corpus callosum and longer and more
      numerous streamlines in the anterior corpus callosum. CONCLUSION: DTI variables
      were not associated with allocation of placebo or thyroid supplementation.
      Markers of poorly organised brain microstructure were associated with low plasma
      FT4 concentrations after birth. The findings suggest that plasma FT4
      concentrations affect brain development in very immature infants and that the
      effect of LT4 supplementation for immature babies with low FT4 plasma
      concentrations warrants further study.

PMID- 24671723
TI  - Gastrointestinal intramural hematoma--analysis of clinical and radiological
      features for early differentiation from mesenteric ischemia.
AB  - INTRODUCTION: Long-term anticoagulation is associated with hemorrhage at various
      sites. Gastrointestinal intramural bleeds and hematomas (IMH) often mimic
      mesenteric ischemia (MI) due to similar clinical settings and imaging features,
      making early differentiation difficult. AIM: To compare the demography, clinical
      features and imaging characteristics of patients presenting with IMH with those
      of MI, so as to help in evolving clinical and imaging guidelines to differentiate
      both early in the course of the disease. METHODS: All radiologically (contrast
      enhanced computed tomogram [CT]) diagnosed cases of gastrointestinal IMH from the
      hospital database during the period between 2006 and 2012 were retrospectively
      analyzed. This data was compared with the clinical and imaging features of a
      group of surgically confirmed MI during the same period. Patients not on
      anticoagulation therapy at the time of presentation and those with incomplete
      clinical or radiological data were excluded from the study. RESULTS: There were
      16 patients in IMH group and 54 patients in MI group. Clinical features like
      overt rectal bleeding or melena, and prolonged prothrombin time-international
      normalized ratio (PT-INR) more than three, and CT features like proximal location
      in the bowel, increased bowel wall thickness, hyperdensity on plain scan (>40
      Hounsfield units (HU)), and short segment bowel involvement were significantly
      associated with IMH. Visualization of embolus and absent mesenteric vasculature
      to a segment of intestine in CT was significantly associated with MI. CONCLUSION:
      Attention to clinical features and early CT scan can aid in early differentiation
      of IMH from MI, facilitating appropriate intervention early in the course of
      disease.

PMID- 24671721
TI  - Diffusion tensor imaging in extremely low birth weight infants managed with
      hypercapnic vs. normocapnic ventilation.
AB  - BACKGROUND: Permissive hypercapnia is a ventilatory strategy used to prevent lung
      injury in ventilated extremely low birth weight (ELBW, birth weight <=1,000 g)
      infants. However, there is retrospective evidence showing that high CO2 is
      associated with brain injury. OBJECTIVE: The objective of this study was to
      compare brain white matter development at term-equivalent age in ELBW infants
      randomized to hypercapnic vs. normocapnic ventilation during the first week of
      life and in healthy non-ventilated term newborns. MATERIALS AND METHODS: Twenty
      two ELBW infants from a randomized controlled trial were included in this study;
      11 received hypercapnic (transcutaneous PCO2 [tcPCO2] 50-60 mmHg) ventilation and
      11 normocapnic (tcPCO2 35-45 mmHg) ventilation during the first week of life
      while still intubated. In addition, ten term healthy newborns served as controls.
      Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was
      performed at term-equivalent age for the ELBW infants and at approximately 2
      weeks of age for the control infants. White matter injury on conventional MRI was
      graded in the ELBW and control infants using a scoring system adopted from
      literature. Tract-based spatial statistics (TBSS) was used to evaluate for
      differences in DTI measured fractional anisotropy (FA, spatially normalized to a
      customized template) among the ELBW and term control infants. RESULTS:
      Conventional MRI white matter scores were not different (7.3 +/- 1.7 vs. 6.9 +/-
      1.4, P = 0.65) between the hypercapnic and normocapnic ELBW infants. TBSS
      analysis did not show significant differences (P < 0.05, corrected) between the
      two ELBW infant groups, although before multiple comparisons correction,
      hypercapnic infants had many regions with lower FA and no regions with higher FA
      (P < 0.05, uncorrected) compared to normocapnic infants. When compared to the
      control infants, normocapnic ELBW infants had a few small regions with
      significantly lower FA, while hypercapnic ELBW infants had more widespread
      regions with significantly lower FA (P < 0.05, fully corrected for multiple
      comparisons). CONCLUSIONS: Normocapnic ventilation vs. permissive hypercapnia may
      be associated with improved white matter development at term-equivalent age in
      ELBW infants. This effect, however, was small and was not apparent on
      conventional MRI. Further research is needed using larger sample sizes to assess
      if permissive hypercapnic ventilation in ELBW infants is associated with worse
      white matter development.

PMID- 24671722
TI  - Growth factors and synaptic plasticity in relapsing-remitting multiple sclerosis.
AB  - During multiple sclerosis (MS) inflammatory attacks, and in subsequent clinical
      recovery phases, immune cells contribute to neuronal and oligodendroglial cell
      survival and tissue repair by secreting growth factors. Animal studies showed
      that growth factors also play a substantial role in regulating synaptic
      plasticity, and namely in long-term potentiation (LTP). LTP could drive clinical
      recovery in relapsing patients by restoring the excitability of denervated
      neurons. We recently reported that maintenance of synaptic plasticity reserve is
      crucial to contrast clinical deterioration in MS and that the platelet-derived
      growth factor (PDGF) may play a key role in its regulation. We also reported that
      a Hebbian form of LTP-like cortical plasticity, explored by paired associative
      stimulation (PAS), correlates with clinical recovery from a relapse in MS. Here,
      we explored the role of PDGF in clinical recovery and in adaptive neuroplasticity
      in relapsing-remitting MS (RR-MS) patients. We found a correlation between the
      cerebrospinal fluid (CSF) PDGF concentrations and the extent of clinical recovery
      after a relapse, as full recovery was more likely observed in patients with high
      PDGF concentrations and poor recovery in subjects with low PDGF levels.
      Consistently with the idea that PDGF-driven synaptic plasticity contributes to
      attenuate the clinical consequences of tissue damage in RR-MS, we also found a
      striking correlation between CSF levels of PDGF and the amplitude of LTP-like
      cortical plasticity explored by PAS. CSF levels of fibroblast growth factor,
      granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor did not correlate with clinical recovery nor with measures of
      synaptic transmission and plasticity. 

PMID- 24671724
TI  - Utility of the "harmless acute pancreatitis score" in predicting a non-severe
      course of acute pancreatitis: a pilot study in an Indian cohort.
AB  - BACKGROUND: Several severity predictors have been tested for assessing acute
      pancreatitis (AP). The recently described harmless acute pancreatitis score
      (HAPS) could be an ideal predictor for Indian patients at the community level. We
      validate this system in the current study. METHODS: This was a prospective pilot
      study conducted at a tertiary center from July 2010 to December 2011. Consecutive
      directly admitted patients over 18 years with a documented first episode of AP
      were enrolled and followed for at least 12 months after discharge/till death.
      HAPS was defined as absence of rebound abdominal tenderness, serum creatinine of
      <2 mg/dL, and hematocrit of <43 for male and <39.6 for female patients at the
      time of admission; and it was considered positive if the patient fulfilled all
      three criteria. Study outcomes included total hospital stay, need for intensive
      care unit (ICU), ICU stay, development of local complications, organ failure,
      hospital-acquired infections (including infected necrosis), and in-hospital
      mortality. RESULTS: There were a total of 103 patients directly admitted with AP
      during the study period, out of which, 23 were excluded. Forty-seven (58.8 %)
      patients were positive for HAPS. Of these, 44 (93.6 %) had an eventual non-severe
      (mild) clinical course with odds ratio 17.6 (95 % CI 4.5-68.3). Sensitivity,
      specificity, positive and negative predictive value, and receiver operating
      characteristics area under the curve of HAPS as a predictor of non-severe disease
      were 76.3 (66.9-86.4), 85.7 (78.0-96.8), 93.8 (88.5-98.6), 56.6 (45.4-73.6), and
      84.8 (76.9-92.7) respectively. CONCLUSION: This study validated the utility of
      HAPS for directly admitted patients with AP in India. Large-scale multicenter
      community-based studies need to be performed.

PMID- 24671725
TI  - Role of Helicobacter pylori in Gastric Neoplasia.
AB  - Helicobacter pylori infection is one of the most important factors in gastric
      carcinogenesis in humans. Epidemiological studies have revealed that H. pylori
      infected patients develop significantly more gastric cancers than uninfected
      individuals. In rodent models, H. pylori inoculation causes strong promoting
      effects in carcinogen-treated animals, whereas the bacterial infection alone
      causes only hyperplasic, atrophic, and/or metaplastic lesions. In both human and
      rodent models, eradication of H. pylori helps inhibit gastric carcinogenesis,
      especially when there is only mild gastric inflammation and no evidence of severe
      atrophy or intestinal metaplasia. Chemoprevention studies in humans have been
      reported and have shown the effectiveness of several medications including a
      cyclooxygenase-2 inhibitor. Candidate chemicals used in rodent models could
      hopefully be used in humans in the future. 

PMID- 24671726
TI  - Multiple firm nodules and tender, indurated plaques.

PMID- 24671727
TI  - Respiratory diseases are associated with molar-incisor hypomineralizations.
AB  - The objective of our study was to evaluate the association of molar-incisor
      hypomineralizations (MIHs) with prospectively collected potential causative
      factors from the first 4 years of life, e.g. respiratory diseases, breastfeeding,
      maternal smoking and parental education. A total of 692 children (10 years old)
      from the GINI birth cohort study participated. The dental examination included
      the registration of enamel hypomineralizations (EHs) according to the EAPD
      criteria. Children with EH were sub-categorized into those with at least one EH
      (MIH/1), those with a minimum of one EH on at least one first permanent molar
      (MIH/2) and those with EH on at least one first permanent molar and a permanent
      incisor (MIH/3). All relationships between causative factors and caries or MIH
      were evaluated using simple and multiple logistic regression analyses. EHs were
      observed in 37.9% (MIH/1), 14.7% (MIH/2) and 9.2% (MIH/3) of all subjects. After
      adjustment for confounding factors, 10-year-old children with at least one
      episode of respiratory disease had a significantly higher risk (2.48 times,
      adjusted OR) for the development of MIH/3. In case of breastfeeding, a non
      significant association was observed. None of the tested factors was associated
      with either MIH/1 or MIH/2. Early respiratory diseases seem to be directly or
      indirectly related to MIH/3 only. The role of (systemic) medications used for
      treatment of these diseases needs to be investigated in future studies.

PMID- 24671729
TI  - Sex work: a comparative study.
AB  - Explanations of adult involvement in sex work typically adopt one of two
      approaches. One perspective highlights a variety of negative experiences in
      childhood and adolescence, including physical and sexual abuse, family
      instability, poverty, associations with "pimps" and other exploiters,
      homelessness, and drug use. An alternative account recognizes that some of these
      factors may be involved, but underscores the contribution of more immediate
      circumstances, such as current economic needs, human capital, and employment
      opportunities. Prior research offers a limited assessment of these contrasting
      claims: most studies have focused exclusively on people working in the sex
      industry and they have not assessed the independent effects of life course
      variables central to these two perspectives. We add to this literature with an
      analysis that drew on insights from life course and life-span development
      theories and considered the contributions of factors from childhood, adolescence,
      and adulthood. Our comparative approach examined predictors of employment in sex
      work relative to two other low-income service or care work occupations: food and
      beverage serving and barbering and hairstyling. Using data from a study of almost
      600 workers from two cities, one in Canada and the other in the United States, we
      found that both immediate circumstances and negative experiences from early life
      are related to current sex work involvement: childhood poverty, abuse, and family
      instability were independently associated with adult sex work, as were limited
      education and employment experience, adult drug use, and marital status. 

PMID- 24671728
TI  - Depression and sexual dysfunction among HIV-positive and HIV-negative men who
      have sex with men: mediation by use of antidepressants and recreational
      stimulants.
AB  - Erectile dysfunction and other forms of sexual dysfunction are highly prevalent
      among HIV+ men who have sex with men (MSM). Research has not previously
      identified the mechanisms by which depression may be associated with sexual
      dysfunction among HIV-positive and HIV-seronegative (HIV-negative) MSM. The
      present study examined the role of antidepressant use, stimulant use, and smoking
      as mediators of the relation between depression and sexual dysfunction among HIV
      positive and HIV-negative MSM. Participants enrolled in the Multicenter AIDS
      Cohort Study, an ongoing prospective study of the natural and treated histories
      of HIV infection among MSM in the United States, completed a modified version of
      the International Index of Erectile Function for MSM. The study sample included
      1,363 participants, with 619 HIV-positive men and 744 HIV-negative men. A
      structural equation model examined depression as a predictor of subsequent sexual
      dysfunction, mediated by antidepressant use, stimulant use, and smoking.
      Depression predicted subsequent sexual function among both HIV-negative and HIV
      positive MSM. This effect appeared to be both a direct effect and an indirect
      effect via antidepressant use. Findings suggest that antidepressant medication
      use may partially explain sexual dysfunction among MSM. 

PMID- 24671731
TI  - A cross-sectional and longitudinal investigation of the external correlates of
      sluggish cognitive tempo and ADHD-inattention symptoms dimensions.
AB  - The objective was to determine if the external correlates of sluggish cognitive
      tempo (SCT) and ADHD-inattention (IN) dimensions were the same in cross-sectional
      and longitudinal analyses. Teachers and aides rated SCT, ADHD-IN, ADHD
      hyperactivity/impulsivity (HI), oppositional defiant disorder (ODD), and
      depression along with academic impairment in 758 Spanish children (55 % boys) on
      three occasions (twice at the end of the first grade year [6-week separation] and
      then again 12-months later at the end of the second grade year). Three of eight
      SCT symptoms showed substantial loadings on the SCT factor and substantially
      higher loadings on the SCT factor than the ADHD-IN factor for teachers and aides
      at each assessment (seems drowsy, thinking is slow, and slow moving). Cross
      sectional and longitudinal analyses yielded similar results with SCT and ADHD-IN
      factors having different and unique external correlates (higher scores on SCT
      predicted lower scores on ADHD-HI and ODD while higher scores on ADHD-IN
      predicted higher scores on ADHD-HI and ODD with SCT and ADHD-IN both uniquely
      predicting academic impairment and depression). Developmental and methodological
      reasons are discussed for the failure to find an inconsistent alertness SCT
      factor (daydreams, alertness fluctuates, absent-minded, loses train of though,
      and confused). 

PMID- 24671732
TI  - In vivo thrombolysis with targeted microbubbles loading tissue plasminogen
      activator in a rabbit femoral artery thrombus model.
AB  - The increasingly high incidence of ischemic stroke caused by thrombosis of the
      arterial vessels is one of the major factors that threaten people's health and
      lives in the world. The present treatments for thrombosis are unsatisfactory yet.
      We developed the microbubbles loading tissue plasminogen activator (tPA) and
      their in vitro thrombolysis efficacy under ultrasound exposure has been proved
      previously. We tried to investigate their thrombolysis effect in vivo in this
      present study. Thrombus model was made by clamping bilateral femoral arteries in
      70 arteries of 40 rabbits. The targeted tPA-loaded microbubbles were made by
      lyophilization, taking arginine-glycine-aspartic acid-serine peptide as the
      targeting ligand. Its thrombolysis efficacy, calculated as count rate and
      efficiency rate of recanalization, was evaluated by Pearson's chi(2) and One-way
      ANOVA, respectively. The count rate of recanalization of the targeted tPA-loaded
      microbubbles under ultrasound exposure (70%) was similar to that of the
      combination of tPA, microbubbles and ultrasound exposure (80%) (P = 0.61), while
      its tPA dosage (0.06 mg/kg) was much less than that of latter (0.9 mg/kg). Its
      efficiency rate of recanalization was the highest among all groups (53.22 +/-
      40.39%) (P < 0.01). Ultrasound-induced targeted tPA-loaded microbubbles release
      is a promising thrombolytic method with satisfactory thrombolytic efficacy,
      lowered tPA dose and potentially decreased hemorrhagic risk.

PMID- 24671734
TI  - Consensually defined facets of personality as prospective predictors of change in
      depression symptoms.
AB  - Depression has robust associations with personality, showing a strong relation
      with neuroticism and more moderate associations with extraversion and
      conscientiousness. In addition, each Big Five domain can be decomposed into
      narrower facets. However, we currently lack consensus as to the contents of Big
      Five facets, with idiosyncrasies across instruments; moreover, few studies have
      examined associations with depression. In the current study, community
      participants completed six omnibus personality inventories; self-reported
      depressive symptoms were assessed at baseline and 5 years later. Exploratory
      factor analyses suggested three to five facets in each domain, and these facets
      served as prospective predictors of depression in hierarchical regressions, after
      accounting for baseline and trait depression. In these analyses, high anger (from
      neuroticism), low positive emotionality (extraversion), low conventionality
      (conscientiousness), and low culture (openness to experiences) were significant
      prospective predictors of depression. Results are discussed in regard to
      personality structure and assessment, as well as personality-psychopathology
      associations.

PMID- 24671733
TI  - Influence of gender on the risk of death and adverse events in patients with
      acute myocardial infarction undergoing pharmacoinvasive strategy.
AB  - Pharmacoinvasive treatment is an acceptable alternative for patients with ST
      segment elevation myocardial infarction (STEMI) in developing countries. The
      present study evaluated the influence of gender on the risks of death and major
      adverse cardiovascular events (MACE) in this population. Seven municipal
      emergency rooms and the Emergency Mobile Healthcare Service in Sao Paulo treated
      STEMI patients with tenecteplase. The patients were subsequently transferred to a
      tertiary teaching hospital for early (<24 h) coronary angiography. A total of 469
      patients were evaluated [329 men (70.1%)]. Compared to men, women had more
      advanced age (60.2 +/- 12.3 vs. 56.5 +/- 11 years; p = 0.002); lower body mass
      index (BMI; 25.85 +/- 5.07 vs. 27.04 +/- 4.26 kg/m2; p = 0.009); higher rates of
      hypertension (70.7 vs. 59.3%, p = 0.02); higher incidence of hypothyroidism (20.0
      vs. 5.5%; p < 0.001), chronic renal failure (10.0 vs. 8.8%; p = 0.68), peripheral
      vascular disease (PVD; 19.3 vs. 4.3%; p = 0.03), and previous history of stroke
      (6.4 vs. 1.3%; p = 0.13); and higher thrombolysis in myocardial infarction risk
      scores (40.0 vs. 23.7%; p < 0.001). The overall in-hospital mortality and MACE
      rates for women versus men were 9.3 versus 4.9% (p = 0.07) and 12.9 versus 7.9%
      (p = 0.09), respectively. By multivariate analysis, diabetes (OR 4.15; 95% CI
      1.86-9.25; p = 0.001), previous stroke (OR 4.81; 95% CI 1.49-15.52; p = 0.009),
      and hypothyroidism (OR 3.75; 95% CI 1.44-9.81; p = 0.007), were independent
      predictors of mortality, whereas diabetes (OR 2.05; 95% CI 1.03-4.06; p = 0.04),
      PVD (OR 2.38; 95% CI 0.88-6.43; p = 0.08), were predictors of MACE. In STEMI
      patients undergoing pharmacoinvasive strategy, mortality and MACE rates were
      twice as high in women; however, this was due to a higher prevalence of risk
      factors and not gender itself.

PMID- 24671735
TI  - Specificity and false positive rates of the Test of Memory Malingering, Rey 15
      item Test, and Rey Word Recognition Test among forensic inpatients with
      intellectual disabilities.
AB  - This study evaluated the specificity and false positive (FP) rates of the Rey 15
      Item Test (FIT), Word Recognition Test (WRT), and Test of Memory Malingering
      (TOMM) in a sample of 21 forensic inpatients with mild intellectual disability
      (ID). The FIT demonstrated an FP rate of 23.8% with the standard quantitative
      cutoff score. Certain qualitative error types on the FIT showed promise and had
      low FP rates. The WRT obtained an FP rate of 0.0% with previously reported cutoff
      scores. Finally, the TOMM demonstrated low FP rates of 4.8% and 0.0% on Trial 2
      and the Retention Trial, respectively, when applying the standard cutoff score.
      FP rates are reported for a range of cutoff scores and compared with published
      research on individuals diagnosed with ID. Results indicated that although the
      quantitative variables on the FIT had unacceptably high FP rates, the TOMM and
      WRT had low FP rates, increasing the confidence clinicians can place in scores
      reflecting poor effort on these measures during ID evaluations. 

PMID- 24671736
TI  - An examination of the measurement equivalence of the Brief Fear of Negative
      Evaluation scale across individuals who identify with an asian ethnicity and
      individuals who identify with a European ethnicity.
AB  - A body of research has demonstrated that individuals with Asian ethnicity endorse
      higher levels of fear of negative evaluation compared with individuals with
      European ethnicity. To date, no study has examined whether this Asian-European
      difference may be confounded by the differential interpretation of the measures
      of fear of negative evaluation by the two groups. The current study thus aimed to
      examine the measurement equivalence of the 12-item Brief Fear of Negative
      Evaluation (BFNE) scale and its 8-item variant composed of straightforwardly
      worded items (BFNE-S) in a sample of individuals who identified with a Chinese
      ethnicity (n = 204) and a sample of individuals who identified with an Anglo
      ethnicity (n = 528). Measurement equivalence across the samples was obtained for
      a two-factor BFNE model and a one-factor BFNE-S model. However, the BFNE-S model
      demonstrated superior fit to the data. Using the BFNE-S, we found that the
      Chinese ethnicity sample scored significantly higher on the latent dimension of
      fear of negative evaluation compared with the Anglo ethnicity sample (d = 0.24).
      These findings disambiguate previous research on Asian-European differences in
      fear of negative evaluation and highlight the need for the continued examination
      of the validity of measures across different ethnicities and cultures. 

PMID- 24671737
TI  - Mediator's Assessment of Safety Issues and Concerns (MASIC): reliability and
      validity of a new intimate partner violence screen.
AB  - We investigated reliability and validity of the Mediator's Assessment of Safety
      Issues and Concerns (MASIC), a screening interview for intimate partner violence
      and abuse (IPV/A) in family mediation settings. Clients at three family mediation
      clinics in the United States and Australia (N = 391) provided reports of the
      other parent's IPV/A. Internal consistency of the total screen was excellent. A
      confirmatory factor analysis provided evidence that the MASIC assesses seven
      types of IPV/A: psychological abuse, coercive controlling behaviors, threats of
      severe violence, physical violence, severe physical violence, sexual violence,
      and stalking. Sex differences on differing types of violence victimization were
      generally consistent with previous research. Higher levels of victimization
      predicted self-reported consequences of abuse (e.g., fear, injuries). More
      abusive parties, as identified by their partners on the MASIC, had more
      Protective Orders and No Contact Orders and criminal convictions and crimes
      potentially related to IPV/A. Results provide initial evidence of the reliability
      and validity of the MASIC but more research is needed.

PMID- 24671739
TI  - Fetal magnetic resonance imaging: jumping from 1.5 to 3 tesla (preliminary
      experience).
AB  - Several attempts have been made at imaging the fetus at 3 T as part of the
      continuous search for increased image signal and better anatomical delineation of
      the developing fetus. Until very recently, imaging of the fetus at 3 T has been
      disappointing, with numerous artifacts impeding image analysis. Better magnets
      and coils and improved technology now allow imaging of the fetus at greater
      magnetic strength, some hurdles in the shape of imaging artifacts
      notwithstanding. In this paper we present the preliminary experience of
      evaluating the developing fetus at 3 T and discuss several artifacts encountered
      and techniques to decrease them, as well as safety concerns associated with
      scanning the fetus at higher magnetic strength.

PMID- 24671741
TI  - Uric acid induces oxidative stress via an activation of the renin-angiotensin
      system in 3T3-L1 adipocytes.
AB  - Hyperuricemia is recently reported involving in various obesity-related
      cardiovascular disorders, especially hypertension. However, the underlying
      mechanisms are not completely understood. In the present study, we investigated
      whether uric acid upregulates renin-angiotensin system (RAS) expression in
      adipocytes. We also examined whether RAS activation plays a role in uric acid
      induced oxidative stress in adipocytes. The adipocytes of different phenotypes
      were incubated with uric acid for 48 h, respectively. Losartan (10(-4) M) or
      captopril (10(-4) M) was used to block adipose tissue RAS activation. mRNA
      expressions of angiotensinogen (AGT), angiotensin-converting enzyme-1 (ACE-1),
      renin, angiotensin type 1 receptor (AT1R), and angiotensin type 2 receptor (AT2R)
      were evaluated with real-time PCR. Angiotensin II concentrations in supernatant
      were measured by ELISA. Intracellular reactive species (ROS) levels were measured
      by fluorescent probe DCFH-DA, DHR, or NBT assay. The uric acid upregulated both
      RAS (AGT, ACE1, renin, AT1R, and AT2R) mRNA expressions and angiotensin II
      protein secretion and caused a significant increase in ROS production in 3T3-L1
      adipocytes. These effects could be prevented by RAS inhibitors, either losartan
      or captopril. RAS activation has been causally implicated in oxidative stress
      induced by uric acid in 3T3-L1 adipocytes, suggesting a plausible mechanism
      through which hyperuricemia contributes to the pathogenesis of obesity-related
      cardiovascular diseases. 

PMID- 24671742
TI  - Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.
AB  - Colorectal cancer is one of the most common cancers in Europe. Over the past few
      decades, important advances have been made in screening, staging and treatment of
      colorectal cancer. However, considerable variation between and within European
      countries remains, which implies that further improvements are possible. The most
      important remaining question now is: when are we, health care professionals,
      delivering the best available care to patients with colon or rectal cancer?
      Currently, quality assurance is a major issue in colorectal cancer care and
      quality assurance awareness is developing in almost all disciplines involved in
      the treatment of colorectal cancer patients. Quality assurance has shown to be
      effective in clinical trials. For example, standardisation and quality control
      were introduced in the Dutch TME trial and led to marked improvements of local
      control and survival in rectal cancer patients. Besides, audit structures can
      also be very effective in monitoring cancer management and national audits showed
      to further improve outcome in colorectal cancer patients. To reduce the
      differences between European countries, an international, multidisciplinary,
      outcome-based quality improvement programme, European Registration of Cancer Care
      (EURECCA), has been initiated. In the near future, the EURECCA dataset will
      perform research on subgroups as elderly patients or patients with comorbidities,
      which are often excluded from trials. For optimal colorectal cancer care, quality
      assurance in guideline formation and in multidisciplinary team management is also
      of great importance. The aim of this review was to create greater awareness and
      to give an overview of quality assurance in the management of colorectal cancer. 

PMID- 24671743
TI  - Cross-modal information integration in category learning.
AB  - An influential theoretical perspective describes an implicit category-learning
      system that associates regions of perceptual space with response outputs by
      integrating information preattentionally and predecisionally across multiple
      stimulus dimensions. In this study, we tested whether this kind of implicit,
      information-integration category learning is possible across stimulus dimensions
      lying in different sensory modalities. Humans learned categories composed of
      conjoint visual-auditory category exemplars comprising a visual component
      (rectangles varying in the density of contained lit pixels) and an auditory
      component (in Exp. 1, auditory sequences varying in duration; in Exp. 2, pure
      tones varying in pitch). The categories had either a one-dimensional, rule-based
      solution or a two-dimensional, information-integration solution. Humans could
      solve the information-integration category tasks by integrating information
      across two stimulus modalities. The results demonstrated an important cross-modal
      form of sensory integration in the service of category learning, and they advance
      the field's knowledge about the sensory organization of systems for
      categorization. 

PMID- 24671744
TI  - The peculiar landscape of repetitive sequences in the olive (Olea europaea L.)
      genome.
AB  - Analyzing genome structure in different species allows to gain an insight into
      the evolution of plant genome size. Olive (Olea europaea L.) has a medium-sized
      haploid genome of 1.4 Gb, whose structure is largely uncharacterized, despite the
      growing importance of this tree as oil crop. Next-generation sequencing
      technologies and different computational procedures have been used to study the
      composition of the olive genome and its repetitive fraction. A total of 2.03 and
      2.3 genome equivalents of Illumina and 454 reads from genomic DNA, respectively,
      were assembled following different procedures, which produced more than 200,000
      differently redundant contigs, with mean length higher than 1,000 nt. Mapping
      Illumina reads onto the assembled sequences was used to estimate their
      redundancy. The genome data set was subdivided into highly and medium redundant
      and nonredundant contigs. By combining identification and mapping of repeated
      sequences, it was established that tandem repeats represent a very large portion
      of the olive genome (~31% of the whole genome), consisting of six main families
      of different length, two of which were first discovered in these experiments. The
      other large redundant class in the olive genome is represented by transposable
      elements (especially long terminal repeat-retrotransposons). On the whole, the
      results of our analyses show the peculiar landscape of the olive genome, related
      to the massive amplification of tandem repeats, more than that reported for any
      other sequenced plant genome.

PMID- 24671747
TI  - Factors mediating the impact of chronic pruritus on quality of life.
AB  - IMPORTANCE: Chronic pruritus is a common problem with a deleterious effect on
      quality of life. The factors mediating the relationship between chronic pruritus
      and quality of life are poorly understood. OBJECTIVE: To determine the factors
      that mediate the impact of chronic pruritus on quality of life. DESIGN, SETTING,
      AND PARTICIPANTS: Cross-sectional study based on a nationwide telephone survey of
      US military veterans sampled from the Veterans Hospital Patient Database.
      Participants were veterans who agreed to participate and were found to have
      chronic pruritus. MAIN OUTCOMES AND MEASURES: Statistical significance of
      predictor variables (characteristics of patients and their chronic pruritus) in
      multivariate analysis using ItchyQoL scores as response variables. RESULTS: Of
      6000 veterans telephoned, 1075 consented to participate; 405 of these had chronic
      pruritus. Factors that mediated the impact of chronic pruritus on quality of life
      were demographic characteristics (age [P = .007], race [P = .05], marital status
      [P = .04]), personality (extroversion [P = .03], neuroticism [P = .01]), pruritus
      characteristics (severity [P < .001], duration [P = .01], frequency [P < .001],
      location [P = .005]), and possible etiology (cutaneous vs systemic [P = .03]).
      Notable factors not found significant include sex (P = .98) and socioeconomic
      variables (education level [P > .99], employment status [P = .53], income [P =
      .62]). CONCLUSIONS AND RELEVANCE: The multitude of factors that significantly
      influence the impact of chronic pruritus on quality of life demonstrates the
      complex nature of this relationship. A better appreciation of these factors will
      improve the clinical evaluation and treatment of chronic pruritus.

PMID- 24671745
TI  - Obligate insect endosymbionts exhibit increased ortholog length variation and
      loss of large accessory proteins concurrent with genome shrinkage.
AB  - Extreme genome reduction has been observed in obligate intracellular insect
      mutualists and is an assumed consequence of fixed, long-term host isolation.
      Rapid accumulation of mutations and pseudogenization of genes no longer vital for
      an intracellular lifestyle, followed by deletion of many genes, are factors that
      lead to genome reduction. Size reductions in individual genes due to small-scale
      deletions have also been implicated in contributing to overall genome shrinkage.
      Conserved protein functional domains are expected to exhibit low tolerance for
      mutations and therefore remain relatively unchanged throughout protein length
      reduction while nondomain regions, presumably under less selective pressures,
      would shorten. This hypothesis was tested using orthologous protein sets from the
      Flavobacteriaceae (phylum: Bacteroidetes) and Enterobacteriaceae (subphylum:
      Gammaproteobacteria) families, each of which includes some of the smallest known
      genomes. Upon examination of protein, functional domain, and nondomain region
      lengths, we found that proteins were not uniformly shrinking with genome
      reduction, but instead increased length variability and variability was observed
      in both the functional domain and nondomain regions. Additionally, as complete
      gene loss also contributes to overall genome shrinkage, we found that the largest
      proteins in the proteomes of nonhost-restricted bacteroidetial and
      gammaproteobacterial species often were inferred to be involved in secondary
      metabolic processes, extracellular sensing, or of unknown function. These
      proteins were absent in the proteomes of obligate insect endosymbionts.
      Therefore, loss of genes encoding large proteins not required for host-restricted
      lifestyles in obligate endosymbiont proteomes likely contributes to extreme
      genome reduction to a greater degree than gene shrinkage. 

PMID- 24671746
TI  - Effects of warfarin and L-carnitine on hemostatic function and oxidative stress
      in streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus (DM) is a complex progressive disease characterized by
      hyperglycemia and a high risk of atherothrombotic disorders affecting the
      coronary, cerebral, and peripheral arterial trees. Oxidative stress is reported
      in diabetic patients. We investigated the hemostatic functions and oxidative
      stress in streptozotocin (STZ)-induced diabetic rats and the effects of warfarin
      and L-carnitine on those parameters. Forty male Sprague-Dawley rats were divided
      into four groups: control, DM, and DM received warfarin or L-carnitine. In all
      rats, blood glucose, insulin, hemoglobin A1c (HbA1c), fibrinogen, factor VII
      (FVII), plasminogen activator inhibitor-1 (PAI-1), fibrin degradation products
      (FDP), protein C, antithrombin III (ATIII), malondialdehydes (MDA), and
      antioxidants (superoxide dismutase, catalase, glutathione peroxidase,
      glutathione) were measured. Also, prothrombin time (PT), activated partial
      thromboplastin time (aPTT), coagulation time, and platelet aggregation were
      evaluated. In diabetic rats, plasma glucose, HbA1c, MDA, fibrinogen, FVII, FDP,
      PAI-1, and platelet aggregation increased while insulin, PT, aPTT, coagulation
      time, protein C, ATIII, and antioxidants decreased. Warfarin administration to
      diabetic rats decreased FVII and FDP and increased PT, aPTT, and coagulation time
      with no effect on MDA, antioxidants, PAI-1, protein C, ATIII, and platelet
      aggregation. On the other hand, L-carnitine decreased fibrinogen, FVII, FDP, PAI
      1, MDA, and platelet aggregation and increased PT, aPTT, coagulation time,
      protein C, ATIII, and antioxidants in diabetic rats. Therefore, we concluded that
      hyperglycemia plays an important role in hypercoagulation state and oxidative
      stress in STZ-induced DM. While L-carnitine improves oxidative stress and
      decreases the hypercoagulation state in DM, warfarin normalizes the
      hypercoagulation state with no effect on oxidative stress. 

PMID- 24671748
TI  - Antibiotics in third molar surgery.
AB  - The aim of this survey was to assess the knowledge and practice of Swiss dentists
      focusing on the use of antibiotics in prophylactic surgical removal of lower
      wisdom teeth. A postal survey was conducted among all 3288 dentists who are
      members of the Swiss Dental Society (SSO) representing nearly all dentists in
      Switzerland. The questionnaire consisted of 13 questions with mostly multiple
      choice answers. Demographic profile, surgical experience, the use of antibiotics,
      and wound management, i.e. wound closure and the use of mouth rinse were
      assessed. A response rate of 55% was obtained. Most Swiss dentists perform
      surgical extractions in their practices. Of all dentists, 18.6% used antibiotics
      routinely, but a large variation was found comparing the three linguistic regions
      of Switzerland with the highest prescription rate of 48% in the French-speaking
      south-west of Switzerland. Fifty-two percent of dentists prescribed amoxicillin
      in a dose of 750 mg. Most often three daily doses were prescribed (47%). A
      postoperative regime was prescribed by 54.4% of dentists. French language
      (p=0.003), graduation from the university of Geneva (p=0.007), foreign diplomas
      (p<0.001), and dentists with diplomas awarded from 2001-2006 (p=0.004) showed a
      highly significant correlation with the use of antibiotics. In Switzerland,
      prophylactic antibiotics are used in third molar surgery. Antibiotic prescription
      however largely depends on geographical situation and dentist profiles. The
      assessment of antibiotic use in private practices is important in the light of
      growing evidence that antibiotic overuse may lead to development of
      multiresistant bacterial strains. In a second part results regarding wound
      management and mouth rinse will be presented.

PMID- 24671749
TI  - Training paraprofessionals to improve socialization in students with ASD.
AB  - An important line of research relates to whether school personnel, such as
      paraprofessionals, who are present during unstructured social periods, such as
      lunch-recess, could successfully implement interventions to improve socialization
      between students with ASD and their typical peers in a group setting. Therefore,
      within the context of a multiple baseline across participants design, we assessed
      whether training paraprofessionals to provide social interventions would enhance
      social development in students with ASD in a group setting. Results showed that
      paraprofessionals who were not providing any social opportunities during baseline
      were able to meet fidelity of implementation following a brief training.
      Consequently, the children with ASD increased their levels of engagement and
      rates of initiation with typically developing peers following intervention.
      Implications for training paraprofessionals to implement effective social
      interventions for students with ASD are discussed. 

PMID- 24671750
TI  - Impact of cognitive behavioral therapy on observed autism symptom severity during
      school recess: a preliminary randomized, controlled trial.
AB  - This study compared cognitive behavioral therapy (CBT) and treatment-as-usual
      (TAU) in terms of effects on observed social communication-related autism symptom
      severity during unstructured play time at school for children with autism
      spectrum disorders (ASD). Thirteen children with ASD (7-11 years old) were
      randomly assigned to 32 sessions of CBT or community-based psychosocial treatment
      (TAU) for 16 weeks. The CBT program is based on the memory retrieval competition
      model and emphasizes the development of perspective-taking through guided
      behavioral experimentation supplemented with reflective Socratic discussion and
      supported by parent training and school consultation to promote generalization of
      social communication and emotion regulation skills. Trained observers blind to
      treatment condition observed each child during recess on two separate days at
      baseline and again at posttreatment, using a structured behavioral observation
      system that generates frequency scores for observed social communication-related
      autism symptoms. CBT outperformed TAU at posttreatment on the frequency of self
      isolation, the proportion of time spent with peers, the frequency of positive or
      appropriate interaction with peers, and the frequency of positive or appropriate
      peer responses to the target child (d effect size range 1.34-1.62). On average,
      children in CBT were engaged in positive or appropriate social interaction with
      peers in 68.6% of observed intervals at posttreatment, compared to 25% of
      intervals for children in TAU. Further investigation of this intervention
      modality with larger samples and follow-up assessments is warranted.

PMID- 24671751
TI  - Palmitoylation is required for intracellular trafficking of influenza B virus NB
      protein and efficient influenza B virus growth in vitro.
AB  - All influenza viruses bud and egress from lipid rafts within the apical plasma
      membrane of infected epithelial cells. As a result, all components of progeny
      virions must be transported to these lipid rafts for assembly and budding.
      Although the mechanism of transport for other influenza proteins has been
      elucidated, influenza B virus (IBV) glycoprotein NB subcellular localization and
      transport are not understood completely. To address the aforementioned properties
      of NB, a series of trafficking experiments were conducted. Here, we showed that
      NB co-localized with markers specific for the endoplasmic reticulum (ER) and
      Golgi region. The data from chemical treatment of NB-expressing cells by
      Brefeldin A, a fungal antibiotic and a known chemical inhibitor of the protein
      secretory pathway, further confirmed that NB is transported through the ER-Golgi
      pathway as it restricted NB localization to the perinuclear region. Using NB
      deletion mutants, the hydrophobic transmembrane domain was identified as being
      required for NB transport to the plasma membrane. Furthermore, palmitoylation was
      also required for transport of NB to the plasma membrane. Systematic mutation of
      cysteines to serines in NB demonstrated that cysteine 49, likely in a
      palmitoylated form, is also required for transport to the plasma membrane.
      Surprisingly, further analysis demonstrated that in vitro replication of NBC49S
      mutant virus was delayed relative to the parental IBV. The results demonstrated
      that NB is the third influenza virus protein to have been shown to be
      palmitoylated and together these findings may aid in future studies aimed at
      elucidating the function of NB.

PMID- 24671752
TI  - Susceptibility of European jackdaws (Corvus monedula) to experimental infection
      with lineage 1 and 2 West Nile viruses.
AB  - Mass bird mortality has been observed in North America after the introduction of
      West Nile virus (WNV), most notably massive die-offs of American crows (Corvus
      brachyrhynchos). In contrast, WNV epidemic activity in Europe has been
      characterized by very low incidences of bird mortality. As the general
      susceptibility of European corvids to strains of WNV remains in question,
      European jackdaws (Corvus monedula) were inoculated with WNV strains circulating
      currently in Greece (Greece-10), Italy (FIN and Ita09) and Hungary (578/10), as
      well as a North American (NY99) genotype with a demonstrated corvid virulence
      phenotype. Infection with all strains except WNV-FIN resulted in mortality.
      Viraemia was observed for birds inoculated with all strains and virus was
      detected in a series of organs upon necropsy. These results suggested that
      jackdaws could potentially function as a sentinel for following WNV transmission
      in Europe; however, elicited viraemia levels might be too low to allow for
      efficient transmission of virus to mosquitoes.

PMID- 24671753
TI  - Perpetuation of H5N1 and H9N2 avian influenza viruses in natural water bodies.
AB  - Water bodies are an important route for the spread and transmission of avian
      influenza virus (AIV). The determining factor for an AIV to transmit through
      diffusion in water is the term of viability of the virus in the water body. To
      better understand the perpetuation of AIV in natural water bodies, and thus the
      risks of AIV spread and transmission via such bodies, we systematically studied
      the inactivation dynamics of two AIV strains (H5N1 and H9N2) at different
      temperatures in water bodies of important migratory bird habitats within China
      (Dongting Lake, Poyang Lake, the Hubei segment of the Yangtze River and Qinghai
      Lake). We also studied the impact of water-borne micro-organisms on the
      perpetuation of AIV. Our findings indicated that water is very likely an
      important route for the epidemic spread of AIV, especially during the autumn and
      winter seasons. In addition, water-borne micro-organisms might antagonize the
      persistence of AIV. 

PMID- 24671754
TI  - Bovine diseases causing neurological signs and death in Mexican feedlots.
AB  - The number of large feedlot operations, similar to that of USA and Canada, has
      notably increased in Mexico in the last three decades. Clinical and laboratory
      diagnoses of neurological diseases in feedlot cattle are crucial in Mexico and
      Central America because of the high incidence of bovine paralytic rabies (BPR).
      Because of its zoonotic potential, BPR must be promptly diagnosed and
      differentiated from other bovine neurological diseases such as thrombotic
      meningoencephalitis (TME), polioencephalomalacia (PEM) and botulism. More
      recently, BPR and botulism have been diagnosed with increasing frequency in
      Mexican feedlots. Neither BPR nor botulism has relevant gross lesions, thus post
      mortem diagnosis without laboratory support is impossible. Herein, we describe
      five outbreaks of neurological diseases in Mexican feedlots in which BPR,
      botulism and PEM were diagnosed either independently or in combination. A diagram
      illustrating the most conspicuous pathologic findings and ancillary laboratory
      test required to confirm the diagnoses of these neurological diseases in feedlot
      cattle is proposed. 

PMID- 24671756
TI  - Neglected tropical skin diseases: their global elimination through integrated
      mass drug administration?

PMID- 24671755
TI  - Characterization of chasmoendolithic community in Miers Valley, McMurdo Dry
      Valleys, Antarctica.
AB  - The Antarctic Dry Valleys are unable to support higher plant and animal life and
      so microbial communities dominate biotic ecosystem processes. Soil communities
      are well characterized, but rocky surfaces have also emerged as a significant
      microbial habitat. Here, we identify extensive colonization of weathered granite
      on a landscape scale by chasmoendolithic microbial communities. A transect across
      north-facing and south-facing slopes plus valley floor moraines revealed 30-100 %
      of available substrate was colonized up to an altitude of 800 m. Communities were
      assessed at a multidomain level and were clearly distinct from those in
      surrounding soils and other rock-inhabiting cryptoendolithic and hypolithic
      communities. All colonized rocks were dominated by the cyanobacterial genus
      Leptolyngbya (Oscillatoriales), with heterotrophic bacteria, archaea, algae, and
      fungi also identified. Striking patterns in community distribution were evident
      with regard to microclimate as determined by aspect. Notably, a shift in
      cyanobacterial assemblages from Chroococcidiopsis-like phylotypes
      (Pleurocapsales) on colder-drier slopes, to Synechococcus-like phylotypes
      (Chroococcales) on warmer-wetter slopes. Greater relative abundance of known
      desiccation-tolerant bacterial taxa occurred on colder-drier slopes. Archaeal
      phylotypes indicated halotolerant taxa and also taxa possibly derived from nearby
      volcanic sources. Among the eukaryotes, the lichen photobiont Trebouxia
      (Chlorophyta) was ubiquitous, but known lichen-forming fungi were not recovered.
      Instead, fungal assemblages were dominated by ascomycetous yeasts. We conclude
      that chasmoendoliths likely constitute a significant geobiological phenomenon at
      lower elevations in granite-dominated Antarctic Dry Valley systems.

PMID- 24671757
TI  - Detection of hemophilia a carriers in Azeri Turkish population of Iran:
      usefulness of HindIII and BclI markers.
AB  - Hemophilia A (HA) is an inherited X-linked coagulation disorder caused by the
      deficiency of factor VIII (FVIII). Linkage analysis is a common indirect method
      for the detection of female carriers in families with HA. In the current study,
      173 patients from 30 unrelated families with HA were recruited from the Azeri
      Turkish population of northwest Iran and analyzed for BclI and HindIII markers by
      polymerase chain reaction-restriction fragment length polymorphism. We
      investigated the potential of using these markers for the detection of mutation
      in carriers through linkage analysis, which would be of tremendous use in
      prenatal diagnosis. Among the tested women, 47% and 35% were found to be
      heterozygous for BclI and HindIII polymorphic markers, respectively. The BclI and
      HindIII markers were informative for the detection of 63% and 17% potential
      carriers, respectively, demonstrating the effectiveness of the BclI marker for
      the detection of HA carriers among the Azeri Turkish population. 

PMID- 24671758
TI  - Macrofollicular variant of papillary thyroid carcinoma with extensive lymph node
      metastases.
AB  - The macrofollicular variant of papillary thyroid carcinoma is a rare subtype of
      the follicular variant of papillary thyroid carcinoma and is usually
      characterized by an indolent clinical course. The tumors are prone to be
      misdiagnosed as benign due to their macrofollicular architecture and bland
      cytologic features. We report a rare case of the macrofollicular variant of
      papillary thyroid carcinoma with extensive lymph node metastases. The patient was
      a 48-year-old female with a right thyroid nodule and multiple enlarged lymph
      nodes in the right neck. It was not possible to make a definitive diagnosis of
      malignancy on fine-needle aspiration cytology and intraoperative frozen section.
      She underwent total thyroidectomy with right modified radical neck dissection.
      The surgical specimen showed a 2.5 * 1.5 * 10 cm, well-circumscribed
      macrofollicular variant of papillary thyroid carcinoma in the right lobe and
      multiple central and right lateral neck lymph node metastases. Molecular testing
      for BRAF, NRAS, HRAS, and KRAS was all negative. We then reviewed the demographic
      and clinicopathologic characteristics of 71 patients with the macrofollicular
      variant of papillary thyroid carcinoma. The cytologic or histopathologic
      diagnosis of macrofollicular variant of papillary thyroid carcinoma can be
      difficult. Extensive lymph node metastases caused by the macrofollicular variant
      of papillary thyroid carcinoma may occur even in the absence of capsular or
      lymphovascular invasion. This review will help to better understand the nature of
      the macrofollicular variant of papillary thyroid carcinoma.

PMID- 24671760
TI  - Efficient generation of mouse ESCs-like pig induced pluripotent stem cells.

PMID- 24671761
TI  - Structural insights into the assembly of the 30S ribosomal subunit in vivo:
      functional role of S5 and location of the 17S rRNA precursor sequence.
AB  - The in vivo assembly of ribosomal subunits is a highly complex process, with a
      tight coordination between protein assembly and rRNA maturation events, such as
      folding and processing of rRNA precursors, as well as modifications of selected
      bases. In the cell, a large number of factors are required to ensure the
      efficiency and fidelity of subunit production. Here we characterize the immature
      30S subunits accumulated in a factor-null Escherichia coli strain (?rsgA?rbfA).
      The immature 30S subunits isolated with varying salt concentrations in the buffer
      system show interesting differences on both protein composition and structure.
      Specifically, intermediates derived under the two contrasting salt conditions
      (high and low) likely reflect two distinctive assembly stages, the relatively
      early and late stages of the 3' domain assembly, respectively. Detailed
      structural analysis demonstrates a mechanistic coupling between the maturation of
      the 5' end of the 17S rRNA and the assembly of the 30S head domain, and
      attributes a unique role of S5 in coordinating these two events. Furthermore, our
      structural results likely reveal the location of the unprocessed terminal
      sequences of the 17S rRNA, and suggest that the maturation events of the 17S rRNA
      could be employed as quality control mechanisms on subunit production and protein
      translation. 

PMID- 24671763
TI  - [Template guided surgery with the open-access software "smop"].
AB  - For many practitioners the pre-implantological work and, thus, the related costs
      have been an obstacle to integrate navigated implantology into their workflow. In
      this article we shed light on a new approach: "smop" reduces the working
      procedure to a minimum. Based on an intuitive planning system implant-prosthetic
      treatment can be carried out with a high degree of predictability as well as
      manageable costs. However, contrary to some opinions the use of the navigation
      template does not automatically lead to better results. It does not automatically
      guarantee the success of the process. To just "blindly" attach the implants
      without surgical experience can lead to fatal consequences. For the seasoned
      implantologist, however, the template is a tool to get the optimum result. As a
      practice for oral surgery and implantology we often receive challenging cases.
      Though we have been practicing for many years and have a lot of experience even
      for us such cases are extraordinarily challenging. Working on such specific cases
      we don't want to work without the three-dimensional diagnostics, the virtual
      implant planning as well as the template based implant insertion anymore.

PMID- 24671762
TI  - The effect of reward on orienting and reorienting in exogenous cuing.
AB  - It is thought that reward-induced motivation influences perceptual, attentional,
      and cognitive control processes to facilitate behavioral performance. In this
      study, we investigated the effect of reward-induced motivation on exogenous
      attention orienting and inhibition of return (IOR). Attention was captured by
      peripheral onset cues that were nonpredictive for the target location.
      Participants performed a target discrimination task at short (170 ms) and long
      (960 ms) cue-target stimulus onset asynchronies. Reward-induced motivation was
      manipulated by exposing participants to low- and high-reward blocks. Typical cue
      facilitation effects on initial orienting were observed for both the low- and
      high-reward conditions. However, IOR was found only for the high-reward
      condition. This indicates that reward-induced motivation has a clear effect on
      reorienting and inhibitory processes following the initial capture of attention,
      but not on initial exogenous orienting that is considered to be exclusively
      automatic and stimulus-driven. We suggest that initial orienting is completely
      data-driven, not affected by top-down motivational processes, while reorienting
      and the accompanying IOR effect involve motivational top-down processes. To
      support this, we showed that reward-induced motivational processes and top-down
      control processes co-act in order to improve behavioral performance: High-reward
      induced motivation caused an increase in top-down cognitive control, as signified
      by posterror slowing. Moreover, we show that personality trait propensity to
      reward-driven behavior (BAS-Drive scale) was related to reward-triggered
      behavioral changes in top-down reorienting, but not to changes in automatic
      orienting. 

PMID- 24671764
TI  - A conserved role for the zinc finger polyadenosine RNA binding protein, ZC3H14,
      in control of poly(A) tail length.
AB  - The ZC3H14 gene, which encodes a ubiquitously expressed, evolutionarily
      conserved, nuclear, zinc finger polyadenosine RNA-binding protein, was recently
      linked to autosomal recessive, nonsyndromic intellectual disability. Although
      studies have been carried out to examine the function of putative orthologs of
      ZC3H14 in Saccharomyces cerevisiae, where the protein is termed Nab2, and
      Drosophila, where the protein has been designated dNab2, little is known about
      the function of mammalian ZC3H14. Work from both budding yeast and flies
      implicates Nab2/dNab2 in poly(A) tail length control, while a role in poly(A) RNA
      export from the nucleus has been reported only for budding yeast. Here we provide
      the first functional characterization of ZC3H14. Analysis of ZC3H14 function in a
      neuronal cell line as well as in vivo complementation studies in a Drosophila
      model identify a role for ZC3H14 in proper control of poly(A) tail length in
      neuronal cells. Furthermore, we show here that human ZC3H14 can functionally
      substitute for dNab2 in fly neurons and can rescue defects in development and
      locomotion that are present in dNab2 null flies. These rescue experiments provide
      evidence that this zinc finger-containing class of nuclear polyadenosine RNA
      binding proteins plays an evolutionarily conserved role in controlling the length
      of the poly(A) tail in neurons. 

PMID- 24671765
TI  - Highly conserved RNA pseudoknots at the Gag-Pol junction of HIV-1 suggest a novel
      mechanism of -1 ribosomal frameshifting.
AB  - -1 programmed ribosomal frameshifting (PRF) is utilized by many viruses to
      synthesize their enzymatic (Pol) and structural (Gag) proteins at a defined
      ratio. For efficient -1 PRF, two cis-acting elements are required: a
      heptanucleotide frameshift site and a downstream stimulator such as a pseudoknot.
      We have analyzed the gag-pol junction sequences from 4254 HIV-1 strains.
      Approximately ninety-five percent of the sequences can form four pseudoknots PK1
      PK4 (~ 97% contain PK1, PK3, and PK4), covering ~ 72 nt including the frameshift
      site. Some pseudoknots are mutually excluded due to sequence overlap. PK1 and PK3
      arrange tandemly. Their stems form a quasi-continuous helix of ~ 22 bp. We
      propose a novel mechanism for possible roles of these pseudoknots. Multiple
      alternative structures may exist at the gag-pol junction. In most strains, the
      PK1-PK3 tandem pseudoknots may dominate the structurally heterogeneous pool of
      RNA due to their greater overall stability. The tandem pseudoknots may function
      as a breaking system to slow down the ribosome. The ribosome unwinds PK1 and stem
      1 of PK3 before it can reach the frameshift site. Then, PK4 can form rapidly
      because the intact stem 2 of PK3 makes up a large part of the stem 1 of PK4. The
      newly formed PK4 jams the entrance of the mRNA tunnel. The process then proceeds
      as in a typical case of -1 PRF. This mechanism incorporates several exquisite new
      features while still being consistent with the current paradigm of pseudoknot
      dependent -1 PRF.

PMID- 24671766
TI  - Rapid identification of mRNA processing defects with a novel single-cell yeast
      reporter.
AB  - It has become increasingly evident that gene expression processes in eukaryotes
      involve communication and coordination between many complex, independent
      macromolecular machines. To query these processes and to explore the potential
      relationships between them in the budding yeast Saccharomyces cerevisiae, we
      designed a versatile reporter using multicolor high-throughput flow cytometry.
      Due to its design, this single reporter exhibits a distinctive signature for many
      defects in gene expression including transcription, histone modification, pre
      mRNA splicing, mRNA export, nonsense-mediated decay, and mRNA degradation.
      Analysis of the reporter in 4967 nonessential yeast genes revealed striking
      phenotypic overlaps between chromatin remodeling, histone modification, and pre
      mRNA splicing. Additionally, we developed a copper-inducible reporter, with which
      we demonstrate that 5-fluorouracil mimics the mRNA decay phenotype of cells
      lacking the 3'-5' exonuclease Rrp6p. Our reporter is capable of performing high
      throughput, rapid, and large-scale screens to identify and characterize genetic
      and chemical perturbations of the major eukaryotic gene expression processes.

PMID- 24671767
TI  - A tRNA body with high affinity for EF-Tu hastens ribosomal incorporation of
      unnatural amino acids.
AB  - There is evidence that tRNA bodies have evolved to reduce differences between
      aminoacyl-tRNAs in their affinity to EF-Tu. Here, we study the kinetics of
      incorporation of L-amino acids (AAs) Phe, Ala allyl-glycine (aG), methyl-serine
      (mS), and biotinyl-lysine (bK) using a tRNA(Ala)-based body (tRNA(AlaB)) with a
      high affinity for EF-Tu. Results are compared with previous data on the kinetics
      of incorporation of the same AAs using a tRNA(PheB) body with a comparatively low
      affinity for EF-Tu. All incorporations exhibited fast and slow phases, reflecting
      the equilibrium fraction of AA-tRNA in active ternary complex with EF-Tu:GTP
      before the incorporation reaction. Increasing the concentration of EF-Tu
      increased the amplitude of the fast phase and left its rate unaltered. This
      allowed estimation of the affinity of each AA-tRNA to EF-Tu:GTP during
      translation, showing about a 10-fold higher EF-Tu affinity for AA-tRNAs formed
      from the tRNA(AlaB) body than from the tRNA(PheB) body. At ~1 uM EF-Tu,
      tRNA(AlaB) conferred considerably faster incorporation kinetics than tRNA(PheB),
      especially in the case of the bulky bK. In contrast, the swap to the tRNA(AlaB)
      body did not increase the fast phase fraction of N-methyl-Phe incorporation,
      suggesting that the slow incorporation of N-methyl-Phe had a different cause than
      low EF-Tu:GTP affinity. The total time for AA-tRNA release from EF-Tu:GDP,
      accommodation, and peptidyl transfer on the ribosome was similar for the
      tRNA(AlaB) and tRNA(PheB) bodies. We conclude that a tRNA body with high EF-Tu
      affinity can greatly improve incorporation of unnatural AAs in a potentially
      generalizable manner. 

PMID- 24671768
TI  - A novel cell death gene acts to repair patterning defects in Drosophila
      melanogaster.
AB  - Cell death is a mechanism utilized by organisms to eliminate excess cells during
      development. Here, we describe a novel regulator of caspase-independent cell
      death, Mabiki (Mabi), that is involved in the repair of the head patterning
      defects caused by extra copies of bicoid in Drosophila melanogaster. Mabiki
      functions together with caspase-dependent cell death mechanisms to provide
      robustness during development. 

PMID- 24671769
TI  - Systems genomics of metabolic phenotypes in wild-type Drosophila melanogaster.
AB  - Systems biology is an approach to dissection of complex traits that explicitly
      recognizes the impact of genetic, physiological, and environmental interactions
      in the generation of phenotypic variation. We describe comprehensive
      transcriptional and metabolic profiling in Drosophila melanogaster across four
      diets, finding little overlap in modular architecture. Genotype and genotype-by
      diet interactions are a major component of transcriptional variation (24 and 5.3%
      of the total variation, respectively) while there were no main effects of diet
      (<1%). Genotype was also a major contributor to metabolomic variation (16%), but
      in contrast to the transcriptome, diet had a large effect (9%) and the
      interaction effect was minor (2%) for the metabolome. Yet specific principal
      components of these molecular phenotypes measured in larvae are strongly
      correlated with particular metabolic syndrome-like phenotypes such as pupal
      weight, larval sugar content and triglyceride content, development time, and
      cardiac arrhythmia in adults. The second principal component of the metabolomic
      profile is especially informative across these traits with glycine identified as
      a key loading variable. To further relate this physiological variability to
      genotypic polymorphism, we performed evolve-and-resequence experiments, finding
      rapid and replicated changes in gene frequency across hundreds of loci that are
      specific to each diet. Adaptation to diet is thus highly polygenic. However, loci
      differentially transcribed across diet or previously identified by RNAi knockdown
      or expression QTL analysis were not the loci responding to dietary selection.
      Therefore, loci that respond to the selective pressures of diet cannot be readily
      predicted a priori from functional analyses. 

PMID- 24671770
TI  - Myelination and oligodendrocyte functions in psychiatric diseases.

PMID- 24671771
TI  - Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study.
AB  - OBJECTIVES: To assess the accuracy of dual-energy CT (DECT) for diagnosing gout,
      and to explore whether it can have any impact on clinical decision making beyond
      the established diagnostic approach using polarising microscopy of synovial fluid
      (diagnostic yield). METHODS: Diagnostic single-centre study of 40 patients with
      active gout, and 41 individuals with other types of joint disease. Sensitivity
      and specificity of DECT for diagnosing gout was calculated against a combined
      reference standard (polarising and electron microscopy of synovial fluid). To
      explore the diagnostic yield of DECT scanning, a third cohort was assembled
      consisting of patients with inflammatory arthritis and risk factors for gout who
      had negative synovial fluid polarising microscopy results. Among these patients,
      the proportion of subjects with DECT findings indicating a diagnosis of gout was
      assessed. RESULTS: The sensitivity and specificity of DECT for diagnosing gout
      was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All
      false negative patients were observed among patients with acute, recent-onset
      gout. All false positive patients had advanced knee osteoarthritis. DECT in the
      diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30
      patients (46.7%). CONCLUSIONS: DECT provides good diagnostic accuracy for
      detection of monosodium urate (MSU) deposits in patients with gout. However,
      sensitivity is lower in patients with recent-onset disease. DECT has a
      significant impact on clinical decision making when gout is suspected, but
      polarising microscopy of synovial fluid fails to demonstrate the presence of MSU
      crystals.

PMID- 24671772
TI  - BRAFV600E-mutation is invariably present and associated to oncogene-induced
      senescence in Erdheim-Chester disease.
AB  - OBJECTIVES: Erdheim-Chester disease (ECD) is a rare form of histiocytosis
      characterised by uncontrolled chronic inflammation. The oncogenic BRAF(V600E)
      mutation has been reported in biopsies in 19 out of 37 patients with ECD from the
      largest published cohort, but never found in the patients' peripheral blood.
      Also, the role of the mutation in the pathogenesis of the disease has not been
      elucidated yet. BRAF(V600E) has been associated with oncogene-induced senescence
      (OIS), a protective mechanism against oncogenic events, characterised by the
      induction of proinflammatory pathways. METHODS: We verified the BRAF status in
      biopsies and peripheral blood from 18 patients with ECD from our cohort and
      matched controls by means of immunohistochemistry and of an ultrasensitive assay,
      based on the combination of a locked nucleic acid PCR and pyrosequencing. Droplet
      digital PCR was used to confirm the findings. We also evaluated the presence of
      senescence markers in ECD histiocytes. RESULTS: BRAF(V600E) mutation was present
      in all the biopsy and peripheral blood samples from patients with ECD and in none
      of the controls. ECD histiocytes and a fraction of circulating monocytes from
      patients with ECD showed signs of a constitutive activation of the MAPK pathway.
      Moreover, BRAF-mutated histiocytes expressed markers of OIS. CONCLUSIONS: The
      oncogenic BRAF(V600E) mutation is present in biopsies and in the peripheral blood
      from all patients with ECD who were evaluated and is associated with OIS. These
      findings have significant implications for the pathogenesis, diagnosis and
      treatment of ECD.

PMID- 24671773
TI  - [Paget's disease of the mandible: a differential diagnosis of the osteomyelitis
      of the jaw].
AB  - Paget's disease of bone is a common, progressive disorder with uncertain
      etiology. It results in the replacement of normal skeletal areas with highly
      vascularized, low density bone. The most frequent symptom is bone pain, which is
      a result of periostal irritation due to increased metabolic activity. However,
      the disease may run without any symptoms. In these cases, an abnormal radiograph
      or an elevated serum alkaline phosphatase can indicate the disorder. Most cases
      are discovered accidentally. The average age of patients at the time of diagnosis
      is about 50 years. Male individuals are preferentially diseased. Paget's disease
      affects either single bone (monostotic) or many bones (polyostotic). It typically
      involves the pelvis, femur and lumbar spine rather than skull and tibia. In the
      head and neck area, the skull is the most frequently affected localization.
      Lesions of the mandible and maxilla are less common. For the therapy of active
      Paget's disease, antiresorptive agents like bisphosphonates are effective drugs.
      Additional treatment with analgesic drugs, antiinflammatory and antineuropathic
      agents is recommended. We present a case of polyostotic Paget's disease of the
      mandible and of the thoracic skeleton.

PMID- 24671774
TI  - A psychometric evaluation of the four-item version of the Control Attitudes Scale
      for patients with cardiac disease and their partners.
AB  - BACKGROUND: The four-item Control Attitudes Scale (CAS) was developed to measure
      control perceived by patients with cardiac disease and their family members, but
      extensive psychometric evaluation has not been performed. OBJECTIVE: The aim was
      to translate, culturally adapt and psychometrically evaluate the CAS in a Swedish
      sample of implantable cardioverter defibrillator (ICD) recipients, heart failure
      (HF) patients and their partners. METHODS: A sample (n=391) of ICD recipients, HF
      patients and partners were used. Descriptive statistics, item-total and inter
      item correlations, exploratory factor analysis, ordinal regression modelling and
      Cronbach's alpha were used to validate the CAS. RESULTS: The findings from the
      factor analyses revealed that the CAS is a multidimensional scale including two
      factors, Control and Helplessness. The internal consistency was satisfactory for
      all scales (alpha=0.74-0.85), except the family version total scale (alpha=0.62).
      No differential item functioning was detected which implies that the CAS can be
      used to make invariant comparisons between groups of different age and sex.
      CONCLUSIONS: The psychometric properties, together with the simple and short
      format of the CAS, make it to a useful tool for measuring perceived control among
      patients with cardiac diseases and their family members. When using the CAS,
      subscale scores should be preferred.

PMID- 24671775
TI  - Amodal completion of unconsciously presented objects.
AB  - In the visual environment, objects often appear behind occluding surfaces, yet
      they are automatically and effortlessly perceived as complete. Here, we examined
      whether visually occluded objects that are presented below the threshold of
      awareness are amodally completed. We used a priming paradigm in which
      participants responded to consciously perceived targets that were preceded by
      unconsciously presented primes. In two experiments, we show that discrimination
      responses to targets were faster when they were preceded by congruent shapes,
      regardless of whether these shapes were intact and complete or occluded by a
      horizontal bar. This priming effect was not produced by a partial match in
      features, since the occluded primes did not facilitate responses to targets that
      shared local features (Experiment 1) or contained only the object features that
      remained visible after occlusion (Experiment 2). These results show that objects
      presented below the threshold of awareness can be amodally completed and provide
      compelling evidence that unconscious processing occurs to a greater extent than
      previously considered. 

PMID- 24671776
TI  - Categorical congruence facilitates multisensory associative learning.
AB  - Learning about objects often requires making arbitrary associations among
      multisensory properties, such as the taste and appearance of a food or the face
      and voice of a person. However, the multisensory properties of individual objects
      usually are statistically constrained, such that some properties are more likely
      to co-occur than others, on the basis of their category. For example, male faces
      are more likely to co-occur with characteristically male voices than with female
      voices. Here, we report evidence that these natural multisensory statistics play
      a critical role in the learning of novel, arbitrary associative pairs. In
      Experiment 1, we found that learning of pairs consisting of human voices and
      gender-congruent faces was superior to learning of pairs consisting of human
      voices and gender-incongruent faces or of pairs consisting of human voices and
      pictures of inanimate objects (plants and rocks). In Experiment 2, we found that
      this "categorical congruency" advantage extended to nonhuman stimuli, as well
      namely, to pairs of class-congruent animal pictures and vocalizations (e.g., dogs
      and barks) versus class-incongruent pairs (e.g., dogs and bird chirps). These
      findings suggest that associating multisensory properties that are statistically
      consistent with the various objects that we encounter in our daily lives is a
      privileged form of learning. 

PMID- 24671777
TI  - Capturing egocentric biases in reference reuse during collaborative dialogue.
AB  - Words that are produced aloud--and especially self-produced ones--are remembered
      better than words that are not, a phenomenon labeled the production effect in the
      field of memory research. Two experiments were conducted to determine whether
      this effect can be generalized to dialogue, and how it might affect dialogue
      management. Triads (Exp. 1) or dyads (Exp. 2) of participants interacted to
      perform a collaborative task. Analyzing reference reuse during the interaction
      revealed that the participants were more likely to reuse the references that they
      had presented themselves, on the one hand, and those that had been accepted
      through verbatim repetition, on the other. Analyzing reference recall suggested
      that the greater accessibility of self-presented references was only transient.
      Moreover, among partner-presented references, those discussed while the
      participant had actively taken part in the conversation were more likely to be
      recalled than those discussed while the participant had been inactive. These
      results contribute to a better understanding of how individual memory processes
      might contribute to collaborative dialogue.

PMID- 24671778
TI  - Benefits of testing for nontested information: retrieval-induced facilitation of
      episodically bound material.
AB  - Testing is a powerful means to boost the retention of information. The extent to
      which the benefits of testing generalize to nontested information, however, is
      not clear. In three experiments, we found that completing cued-recall tests for a
      subset of studied materials enhanced retention for the specific information
      tested, as well as for associated, nontested information during later free-recall
      testing. In Experiment 1, this generalized benefit was revealed for lists of
      category-exemplar pairs. Experiment 2 extended the effect to unrelated words,
      suggesting that retrieval can enhance later free recall of nontested information
      that is bound solely through episodic context. In Experiment 3, we manipulated
      the format of the final test and found facilitation in free-recall, but not in
      cued-recall, testing. The results suggest that testing may facilitate later free
      recall in part by enhancing access to information that is present during a prior
      temporal or list context. More generally, these findings suggest that retrieval
      induced facilitation extends to a broader range of conditions than has previously
      been suggested, and they further motivate the adoption of testing as a practical
      and effective learning tool. 

PMID- 24671779
TI  - Evaluation of the Remel RapID NF plus rapid biochemical method for identification
      of Burkholderia pseudomallei.
AB  - Typical methods for the identification of Burkholderia pseudomallei colonies
      produce results in 18 h. The Remel RapID NF Plus kit produces results in 4 h. We
      used the kit for 190 stored B. pseudomallei isolates and correctly identified 189
      of them. This kit produces consistent results for known B. pseudomallei isolates.

PMID- 24671780
TI  - Rapid detection of New Delhi metallo-beta-lactamase gene and variants coding for
      carbapenemases with different activities by use of a PCR-based in vitro protein
      expression method.
AB  - New Delhi metallo-beta-lactamase (NDM)-producing bacteria are considered
      potential global health threats. It is necessary to monitor NDM-1 and its
      variants in clinical isolates in order to understand the NDM-1 epidemic and the
      impact of its variants on beta-lactam resistance. To reduce the lengthy time
      needed for cloning and expression of NDM-1 variants, a novel PCR-based in vitro
      protein expression (PCR-P) method was used to detect blaNDM-1 and its variants
      coding for carbapenemases with different activities (functional variants). The
      PCR-P method combined a long-fragment real-time quantitative PCR (LF-qPCR) with
      in vitro cell-free expression to convert the blaNDM-1 amplicons into NDM for
      carbapenemase assay. The method could screen for blaNDM-1 within 3 h with a
      detection limit of 5 copies and identify functional variants within 1 day. Using
      the PCR-P to analyze 5 recent blaNDM-1 variants, 2 functional variants, blaNDM-4
      and blaNDM-5, were revealed. In the initial testing of 23 clinical isolates, the
      PCR-P assay correctly found 8 isolates containing blaNDM-1. This novel method
      provides the first integrated approach for rapidly detecting the full-length
      blaNDM-1 and revealing its functional variants in clinical isolates. 

PMID- 24671781
TI  - In vitro antimicrobial susceptibility of Aerococcus urinae.
AB  - Aerococcus urinae may cause urinary tract infections, bacteremia, and
      endocarditis. No standardized susceptibility test methods or interpretive
      criteria have been proposed for this organism. This study reports the MIC results
      for 128 A. urinae isolates tested by broth microdilution. The isolates had low
      MICs to amoxicillin, cefotaxime, ceftriaxone, doxycycline, linezolid, meropenem,
      penicillin, rifampin, tetracycline, trimethoprim-sulfamethoxazole, and
      vancomycin. However, 55% of the isolates had MICs to clindamycin of >0.25 MUg/ml,
      44% had MICs to erythromycin of >0.25 MUg/ml, and 16% had MICs to levofloxacin of
      >2 MUg/ml. 

PMID- 24671782
TI  - Beta-hemolytic, multi-lancefield antigen-agglutinating Enterococcus durans from a
      pregnant woman, mimicking Streptococcus agalactiae.
AB  - A beta-hemolytic Lancefield antigen A-, B-, C-, D-, F-, and G-positive
      Enterococcus durans strain was cultivated from the rectovaginal swab of a
      pregnant woman who underwent antenatal screening for Streptococcus agalactiae.
      The isolate raised concern as to what extent similar strains are misrecognized
      and lead to false diagnosis of group B streptococci. 

PMID- 24671783
TI  - Ureaplasma parvum prosthetic joint infection detected by PCR.
AB  - We describe the first reported case of Ureaplasma parvum prosthetic joint
      infection (PJI) detected by PCR. Ureaplasma species do not possess a cell wall
      and are usually associated with colonization and infection of mucosal surfaces
      (not prosthetic material). U. parvum is a relatively new species name for certain
      serovars of Ureaplasma urealyticum, and PCR is useful for species determination.
      Our patient presented with late infection of his right total knee arthroplasty.
      Intraoperative fluid and tissue cultures and pre- and postoperative synovial
      fluid cultures were all negative. To discern the pathogen, we employed PCR
      coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). Our
      patient's failure to respond to empirical antimicrobial treatment and our
      previous experience with PCR/ESI-MS in culture-negative cases of infection
      prompted us to use this approach over other diagnostic modalities. PCR/ESI-MS
      detected U. parvum in all samples. U. parvum-specific PCR testing was performed
      on all synovial fluid samples to confirm the U. parvum detection. 

PMID- 24671784
TI  - Assessment of antigen and molecular tests with serial specimens from a patient
      with influenza A(H7N9) infection.

PMID- 24671785
TI  - First report of emerging zoonotic pathogen Wohlfahrtiimonas chitiniclastica in
      the United States.
AB  - Wohlfahrtiimonas chitiniclastica is an emerging human pathogen that has been
      identified as the cause of septicemia in humans in Europe and South America. Here
      we report the first case of a unique disease manifestation of Wohlfahrtiimonas
      chitiniclastica-induced bacterial septicemia secondary to wound myiasis in a deer
      in Michigan in the United States. 

PMID- 24671786
TI  - Novel DNA chip based on a modified DigiTag2 assay for high-throughput species
      identification and genotyping of Mycobacterium tuberculosis complex isolates.
AB  - A multipurpose high-throughput genotyping tool for the assessment of recent
      epidemiological data and evolutional pattern in Mycobacterium tuberculosis
      complex (MTBC) clinical isolates was developed in this study. To facilitate
      processing, 51 highly informative single nucleotide polymorphisms (SNPs) were
      selected for discriminating the clinically most relevant MTBC species and
      genotyping M. tuberculosis into its principle genetic groups (PGGs) and SNP
      cluster groups (SCGs). Because of the high flexibility of the DigiTag2 assay, the
      identical protocol and DNA array containing the identical set of probes were
      applied to the highly GC-rich mycobacterial genome. The specific primers with
      multiplex amplification and hybridization conditions based on the DigiTag2
      principle were optimized and evaluated with 14 MTBC reference strains, 4
      nontuberculous mycobacteria (NTM) isolates, and 322 characterized M. tuberculosis
      clinical isolates. The DNA chip that was developed revealed a 99.85% call rate, a
      100% conversion rate, and 99.75% reproducibility. For the accuracy rate, 98.94%
      of positive calls were consistent with previous molecular characterizations. Our
      cost-effective technology was capable of simultaneously identifying the MTBC
      species and the genotypes of 96 M. tuberculosis clinical isolates within 6 h
      using only simple instruments, such as a thermal cycler, a hybridization oven,
      and a DNA chip scanner, and less technician skill was required than for other
      techniques. We demonstrate this approach's potential as a simple, flexible, and
      rapid tool for providing clearer information regarding circulating MTBC isolates.

PMID- 24671787
TI  - Comparative study of traditional flagellum serotyping and liquid chromatography
      tandem mass spectrometry-based flagellum typing with clinical Escherichia coli
      isolates.

PMID- 24671788
TI  - Multiplex nucleic acid amplification test for diagnosis of dengue fever, malaria,
      and leptospirosis.
AB  - Dengue, leptospirosis, and malaria are among the most common etiologies of
      systemic undifferentiated febrile illness (UFI) among travelers to the developing
      world, and these pathogens all have the potential to cause life-threatening
      illness in returned travelers. The current study describes the development of an
      internally controlled multiplex nucleic acid amplification test for the detection
      of dengue virus (DENV) and Leptospira and Plasmodium species, with a specific
      callout for Plasmodium falciparum (referred to as the UFI assay). During
      analytical evaluation, the UFI assay displayed a wide dynamic range and a
      sensitive limit of detection for each target, including all four DENV serotypes.
      In a clinical evaluation including 210 previously tested samples, the
      sensitivities of the UFI assay were 98% for DENV (58/59 samples detected) and
      100% for Leptospira and malaria (65/65 and 20/20 samples, respectively). Malaria
      samples included all five Plasmodium species known to cause human disease. The
      specificity of the UFI assay was 100% when evaluated with a panel of 66 negative
      clinical samples. Furthermore, no amplification was observed when extracted
      nucleic acids from related pathogens were tested. Compared with whole-blood
      samples, the UFI assay remained positive for Plasmodium in 11 plasma samples from
      patients with malaria (parasitemia levels of 0.0037 to 3.4%). The syndrome-based
      design of the UFI assay, combined with the sensitivities of the component tests,
      represents a significant improvement over the individual diagnostic tests
      available for these pathogens. 

PMID- 24671789
TI  - Optimal positive cutoff points for careHPV testing of clinician- and self
      collected specimens in primary cervical cancer screening: an analysis from rural
      China.
AB  - careHPV, a lower-cost DNA test for human papillomavirus (HPV), is being
      considered for cervical cancer screening in low- and middle-income countries.
      However, not a single large-scaled study exists to investigate the optimal
      positive cutoff point of careHPV test. We pooled data for 9,785 women
      participating in two individual studies conducted from 2007 to 2011 in rural
      China. Woman underwent multiple screening tests, including careHPV on clinician
      collected specimens (careHPV-C) and self-collected specimens (careHPV-S), and
      Hybrid Capture 2 on clinician-collected specimens (HC2-C) as a reference
      standard. The primary endpoint was cervical intraepithelial neoplasia grade 3 or
      more severe (CIN3+) (n = 127), and secondary endpoint was CIN2+ (n = 213). The
      area under the curves (AUCs) for HC2-C and careHPV-C were similar (0.954 versus
      0.948, P = 0.166), and better than careHPV-S (0.878; P < 0.001 versus both). The
      optimal positive cutoff points for HC2-C, careHPV-C, and careHPV-S were 1.40,
      1.74, and 0.85, respectively. At the same cutoff point, careHPV-C was not
      significantly less sensitive and more specific for CIN3+ than HC2-C, and careHPV
      S was significantly less sensitive for CIN3+ than careHPV-C and HC2-C. Raising
      the cutoff point of careHPV-C from 1.0 to 2.0 could result in nonsignificantly
      lower sensitivity but significantly higher specificity. Similar results were
      observed using CIN2+ endpoint. careHPV using either clinician- or self-collected
      specimens performed well in detecting cervical precancer and cancer. We found
      that the optimal cutoff points of careHPV were 2.0 on clinician-collected
      specimens and 1.0 on self-collected specimens. 

PMID- 24671790
TI  - Multicenter evaluation of the Quidel Lyra Direct C. difficile nucleic acid
      amplification assay.
AB  - Clostridium difficile is a Gram-positive bacterium commonly found in health care
      and long-term-care facilities and is the most common cause of antibiotic
      associated diarrhea. Rapid detection of this bacterium can assist physicians in
      implementing contact precautions and appropriate antibiotic therapy in a timely
      manner. The purpose of this study was to compare the clinical performance of the
      Quidel Lyra Direct C. difficile assay (Lyra assay) (Quidel, San Diego, CA) to
      that of a direct cell culture cytotoxicity neutralization assay (CCNA) and
      enhanced toxigenic culture. This study was performed at three geographically
      diverse laboratories within the United States using residual stool specimens
      submitted for routine C. difficile testing. Residual samples were tested using
      the Lyra assay on three real-time PCR platforms, and results were compared to
      those for direct CCNA and enhanced toxigenic culture. The test results for all
      platforms were consistent across all three test sites. The sensitivity and
      specificity of the Lyra assay on the SmartCycler II, ABI 7500 Fast DX, and ABI
      QuantStudio DX instruments compared to CCNA were 90.0% and 93.3%, 95.0% and
      94.2%, and 93.8% and 95.0%, respectively. Compared to enhanced toxigenic culture,
      the sensitivity and specificity of the Lyra assay on the SmartCycler II, ABI
      7500, and QuantStudio instruments were 82.1% and 96.9%, 89.3% and 98.8%, and
      85.7% and 99.0%, respectively. Overall, the Lyra assay is easy to use and
      versatile and compares well to C. difficile culture methods. 

PMID- 24671791
TI  - Ability of two commercially available assays (Abbott RealTime HIV-1 and Roche
      Cobas AmpliPrep/Cobas TaqMan HIV-1 Version 2.0) to quantify low HIV-1 RNA Levels
      (<1,000 copies/milliliter): comparison with clinical samples and NIBSC working
      reagent for nucleic acid testing assays.
AB  - Concordance between molecular assays may be suboptimal at low HIV-1 viremia
      levels (<1,000 copies/ml); therefore, it may be difficult to define and compare
      virologic endpoints for successful and failed therapy. We compared two commercial
      assays (the Abbott RealTime HIV-1 and the Roche Cobas AmpliPrep/TaqMan HIV-1
      version 2.0) for their ability to detect and quantify low viral loads. A
      comparison was performed using 167 residual clinical samples (with values ranging
      from "not detected" to 1,000 copies/ml, as measured by the Abbott assay) and the
      National Institute and Biological Standards and Control (NIBSC) HIV-1 RNA working
      reagent 1 for nucleic acid amplification techniques (NAT) assays (serially
      diluted to a range from 1 to 1,000 copies/ml). Quantitative results were compared
      using Lin's concordance correlation coefficient and a Bland-Altman plot.
      Concordance with the qualitative results was measured by Cohen's kappa statistic.
      With clinical samples, the degree of interassay concordance of the qualitative
      results at a 40-copies/ml HIV-1 RNA threshold was substantial (kappa = 0.762);
      the correlation among the quantified samples was suboptimal (concordance
      correlation coefficient, 0.728; P < 0.0001); the mean difference of the values
      between the Roche and Abbott assays was 0.193 log10 copies/ml. Using the HIV-1
      RNA working reagent 1 for NAT assays, the results provided by the Roche assay
      were, on average, 3 times higher than expected, while the Abbott assay showed
      high accuracy. The Roche assay was highly sensitive, being able to detect a level
      as low as 3.5 copies/ml HIV-1 RNA with 95% probability. The performance
      characteristics of each molecular assay should be taken into account when HIV-1
      RNA threshold values for "virologic suppression," "virologic failure,"
      "persistent low viral loads," etc., are defined and indicated in the support of
      clinical decisions. 

PMID- 24671792
TI  - Significantly higher cytokine and chemokine levels in patients with Japanese
      spotted fever than in those with Tsutsugamushi disease.
AB  - Tetracyclines are administered to cure Japanese spotted fever (JSF) and
      tsutsugamushi disease (TD). It is generally said that the clinical course of JSF
      is worse than that of TD despite antibiotic treatment. The precise mechanism
      underlying the more severe clinical course of JSF is not fully understood. We
      therefore examined whether the differential cytokine profile between these two
      infectious diseases contributes to the difference in clinical severity. The serum
      concentrations of various cytokines (tumor necrosis factor alpha [TNF-alpha],
      interleukin-6 [IL-6], and gamma interferon [IFN-gamma]) and chemokines (IL-8,
      interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP
      1], macrophage inflammatory protein 1alpha [MIP-1alpha], MIP-1beta, and eotaxin)
      were measured in 32 TD and 21 JSF patients. The results showed that serum levels
      of TNF-alpha in the acute phases of TD and JSF were significantly increased, with
      a higher concentration of TNF-alpha in patients with JSF (mean, 39.9 pg/ml) than
      in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other
      cytokines and chemokines (IL-6, IFN-gamma, IL-8, IP-10, MCP-1, MIP-1alpha, and
      MIP-1beta) were also observed in the acute phase of JSF. The clinical severity
      score (3.67 +/- 1.71) of JSF patients was higher than that of TD patients (1.47
      +/- 0.77). Our findings revealed that the cytokine and chemokine levels in the
      acute phase of JSF were significantly higher than those in the acute phase of TD.
      The differential cytokine levels may be related to the difference in clinical
      severity between JSF and TD. 

PMID- 24671793
TI  - Typing and clustering of Yersinia pseudotuberculosis isolates by restriction
      fragment length polymorphism analysis using insertion sequences.
AB  - Yersinia pseudotuberculosis is an enteropathogen that has an animal reservoir and
      causes human infections, mostly in temperate and cold countries. Most of the
      methods previously used to subdivide Y. pseudotuberculosis were performed on
      small numbers of isolates from a specific geographical area. One aim of this
      study was to evaluate the typing efficiency of restriction fragment length
      polymorphism of insertion sequence hybridization patterns (IS-RFLP) compared to
      other typing methods, such as serotyping, ribotyping, and multilocus sequence
      typing (MLST), on the same set of 80 strains of Y. pseudotuberculosis of global
      origin. We found that IS100 was not adequate for IS-RFLP but that both IS285 and
      IS1541 efficiently subtyped Y. pseudotuberculosis. The discriminatory index (DI)
      of IS1541-RFLP (0.980) was superior to those of IS285-RFLP (0.939), ribotyping
      (0.944), MLST (0.861), and serotyping (0.857). The combination of the two IS (2IS
      RFLP) further increased the DI to 0.998. Thus, IS-RFLP is a powerful tool for the
      molecular typing of Y. pseudotuberculosis and has the advantage of exhibiting
      well-resolved banding patterns that allow for a reliable comparison of strains of
      worldwide origin. The other aim of this study was to assess the clustering power
      of IS-RFLP. We found that 2IS-RFLP had a remarkable capacity to group strains
      with similar genotypic and phenotypic markers, thus identifying robust
      populations within Y. pseudotuberculosis. Our study thus demonstrates that 2IS-
      and even IS1541-RFLP alone might be valuable tools for the molecular typing of
      global isolates of Y. pseudotuberculosis and for the analysis of the population
      structure of this species. 

PMID- 24671794
TI  - Cytomegalovirus in bone marrow cells correlates with cytomegalovirus in
      peripheral blood leukocytes.
AB  - In allogeneic hematopoietic stem cell transplant recipients with bone marrow (BM)
      suppression, cytomegalovirus (CMV) pp65 antigenemia and DNA were detectable in
      peripheral blood leukocytes (PBL) and BM cells. A relationship between CMV
      infection of PBL and BM cells has been found. 

PMID- 24671795
TI  - Clonal relationship and differentiation among Mycobacterium abscessus isolates as
      determined using the semiautomated repetitive extragenic palindromic sequence PCR
      based DiversiLab system.
AB  - Mycobacterium abscessus is a rapidly growing mycobacterium that causes
      respiratory tract infections in predisposed patients, such as those with cystic
      fibrosis and nosocomial skin and soft tissue infections. In order to investigate
      the clonal relationships between the strains causing epidemic episodes, we
      evaluated the discriminatory power of the semiautomated DiversiLab (DL)
      repetitive extragenic palindromic sequence PCR (REP-PCR) test for M. abscessus
      genotyping. Since M. abscessus was shown to be composed of subspecies (M.
      abscessus subsp. massiliense, M. abscessus subsp. bolletii, and M. abscessus
      subsp. abscessus), we also evaluated the ability of this technique to
      differentiate subspecies. The technique was applied to two collections of
      clinical isolates, (i) 83 M. abscessus original isolates (43 M. abscessus subsp.
      abscessus, 12 M. abscessus subsp. bolletii, and 28 M. abscessus subsp.
      massiliense) from infected patients and (ii) 35 repeated isolates obtained over 1
      year from four cystic fibrosis patients. The DL REP-PCR test was standardized for
      DNA extraction, DNA amplification, and electrophoresis pattern comparisons. Among
      the isolates from distinct patients, 53/83 (62%) isolates showed a specific
      pattern, and 30 were distributed in 11 clusters and 6 patterns, with 2 to 4
      isolates per pattern. The clusters and patterns did not fully correlate with
      multilocus sequence typing (MLST) analysis results. This revealed a high genomic
      diversity between patients, with a discriminatory power of 98% (Simpson's
      diversity index). However, since some isolates shared identical patterns, this
      raises the question of whether it is due to transmission between patients or a
      common reservoir. Multiple isolates from the same patient showed identical
      patterns, except for one patient infected by two strains. Between the M.
      abscessus subspecies, the indexes were <70%, indicating that the DL REP-PCR test
      is not an accurate tool for identifying organisms to the subspecies level. REP
      PCR appears to be a rapid genotyping method that is useful for investigating
      epidemics of M. abscessus infections. 

PMID- 24671796
TI  - Molecular epidemiology of sil locus in clinical Streptococcus pyogenes strains.
AB  - Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide variety of
      diseases, ranging from mild noninvasive to severe invasive infections. Mutations
      in regulatory components have been implicated in the switch from colonization to
      invasive phenotypes. The inactivation of the sil locus, composed of six genes
      encoding a quorum-sensing complex, gives rise to a highly invasive strain.
      However, studies conducted on limited collections of GAS strains suggested that
      sil prevalence is around 15%; furthermore, whereas a correlation between the
      presence of sil and the genetic background was suggested, no link between the
      presence of a functional sil locus and the invasive status was assessed. We
      established a collection of 637 nonredundant strains covering all emm genotypes
      present in France and of known clinical history; 68%, 22%, and 10% were from
      invasive infections, noninvasive infections, and asymptomatic carriage,
      respectively. Among the 637 strains, 206 were sil positive. The prevalence of the
      sil locus varied according to the emm genotype, being present in >85% of the
      emm4, emm18, emm32, emm60, emm87, and emm90 strains and absent from all emm1,
      emm28, and emm89 strains. A random selection based on 2009 French epidemiological
      data indicated that 16% of GAS strains are sil positive. Moreover, due to
      mutations leading to truncated proteins, only 9% of GAS strains harbor a
      predicted functional sil system. No correlation was observed between the presence
      or absence of a functional sil locus and the strain invasiveness status. 

PMID- 24671797
TI  - Massive parallel sequencing provides new perspectives on bacterial brain
      abscesses.
AB  - Rapid development within the field of massive parallel sequencing (MPS) is about
      to bring this technology within reach for diagnostic microbiology laboratories.
      We wanted to explore its potential for improving diagnosis and understanding of
      polymicrobial infections, using bacterial brain abscesses as an example. We
      conducted a prospective nationwide study on bacterial brain abscesses. Fifty-two
      surgical samples were included over a 2-year period. The samples were categorized
      as either spontaneous intracerebral, spontaneous subdural, or postoperative.
      Bacterial 16S rRNA genes were amplified directly from the specimens and sequenced
      using Ion Torrent technology, with an average of 500,000 reads per sample. The
      results were compared to those from culture- and Sanger sequencing-based
      diagnostics. Compared to culture, MPS allowed for triple the number of bacterial
      identifications. Aggregatibacter aphrophilus, Fusobacterium nucleatum, and
      Streptococcus intermedius or combinations of them were found in all spontaneous
      polymicrobial abscesses. F. nucleatum was systematically detected in samples with
      anaerobic flora. The increased detection rate for Actinomyces spp. and
      facultative Gram-negative rods further revealed several species associations. We
      suggest that A. aphrophilus, F. nucleatum, and S. intermedius are key pathogens
      for the establishment of spontaneous polymicrobial brain abscesses. In addition,
      F. nucleatum seems to be important for the development of anaerobic flora. MPS
      can accurately describe polymicrobial specimens when a sufficient number of reads
      is used to compensate for unequal species concentrations and principles are
      defined to discard contaminant bacterial DNA in the subsequent data analysis.
      This will contribute to our understanding of how different types of polymicrobial
      infections develop. 

PMID- 24671798
TI  - Performance of galactomannan, beta-d-glucan, Aspergillus lateral-flow device,
      conventional culture, and PCR tests with bronchoalveolar lavage fluid for
      diagnosis of invasive pulmonary aspergillosis.
AB  - Galactomannan detection in bronchoalveolar lavage (BAL) fluid samples (GM test)
      is currently considered the gold standard test for diagnosing invasive pulmonary
      aspergillosis (IPA). The limitations, however, are the various turnaround times
      and availability of testing. We compared the performance of GM testing with that
      of conventional culture, an Aspergillus lateral-flow-device (LFD) test, a beta-d
      glucan (BDG) test, and an Aspergillus PCR assay by using BAL fluid samples from
      immunocompromised patients. A total of 78 BAL fluid samples from 78 patients at
      risk for IPA (74 samples from Graz and 4 from Mannheim) collected between
      December 2012 and May 2013 at two university hospitals in Austria and Germany
      were included. Three patients had proven IPA, 14 probable IPA, and 17 possible
      IPA, and 44 patients had no IPA. The diagnostic accuracies of the different
      methods for probable/proven IPA were evaluated. The diagnostic odds ratios were
      the highest for the GM, PCR, and LFD tests. The sensitivities for the four
      methods (except culture) were between 70 and 88%. The combination of the GM
      (cutoff optical density index [ODI], >1.0) and LFD tests increased the
      sensitivity to 94%, while the combination of the GM test (>1.0) and PCR resulted
      in 100% sensitivity (specificity for probable/proven IPA, 95 to 98%). The
      performance of conventional culture was limited by low sensitivity, while that of
      the BDG test was limited by low specificity. We evaluated established and novel
      diagnostic methods for IPA and found that the Aspergillus PCR, LFD, and GM tests
      were the most useful methods for diagnosing the disease by using BAL fluid
      samples. In particular, the combination of the GM test and PCR or, if PCR is not
      available, the LFD test, allows for sensitive and specific diagnosis of IPA. 

PMID- 24671799
TI  - Serological identification and prevalence of a novel O-antigen epitope linked to
      3- and 4-O-acetylated rhamnose III of lipopolysaccharide in Shigella flexneri.
AB  - Shigella flexneri is the major cause of shigellosis in developing countries. All
      serotypes except for serotype 6 share an O-antigen backbone composed of a -> 2)
      alpha-L-Rhap(III)-(1 -> 2)-alpha-l-Rhap(II)-(1 -> 3)-alpha-l-Rhap(I)-(1 -> 3)
      beta-D-GlcpNAc-(1 -> tetrasaccharide repeat. It can be modified by the addition
      of a glucosyl group to one or more sugar residues and/or an O-acetyl group to
      Rha(I) and/or a phosphoethanolamine to Rha(II) and/or Rha(III). These
      modifications give rise to type I-, IC-, II-, IV-, and V- and to group 6-, 7,8-,
      and MASF IV-1-specific antigenic determinants, which comprise the current
      serotyping scheme of S. flexneri. Recently, another O-antigen modification
      created by adding an O-acetyl group to Rha(III) at position 3 or 4 (3/4-O
      acetylation) has been found in S. flexneri serotypes 1a, 1b, 2a, 5a, Y, and 6. A
      new O-acyltransferase gene named oacB has been shown to mediate the 3/4-O
      acetylation in serotypes 1a, 1b, 2a, 5a, and Y but not in 6. In this work, we
      studied the distribution of the 3/4-O-acetylation in S. flexneri and the
      antigenicity that resulted from this modification. PCR screening of the oacB gene
      in clinical isolates of S. flexneri demonstrated that the oacB-mediated 3/4-O
      acetylation is widespread in serotypes 1a, 1b, 2a, 5a, and Y. Serological
      analysis indicated that this modification confers the host with a novel antigenic
      determinant that is provisionally named group O factor 9. These findings enhance
      our understanding of the varieties of O-antigenic determinants related to O
      antigen modification in S. flexneri and will assist epidemiological studies and
      vaccine development.

PMID- 24671800
TI  - Catheter-related bloodstream infection by Tsukamurella inchonensis in an
      immunocompromised patient.
AB  - We report a case of catheter-related bloodstream infection by Tsukamurella
      inchonensis, identified using 16S rRNA gene sequencing, in a patient with
      myelofibrosis who underwent a bone marrow transplant. Tsukamurella species
      infections are rare. To our knowledge, this is the first case of T. inchonensis
      bloodstream infection in an immunocompromised patient. 

PMID- 24671801
TI  - Comparison of pulsed-gel electrophoresis and a commercial repetitive-element PCR
      method for assessment of methicillin-resistant Staphylococcus aureus clustering
      in different health care facilities.
AB  - Pulsed-field gel electrophoresis (PFGE) is a common method used to type
      methicillin-resistant Staphylococcus aureus (MRSA) in nosocomial investigations
      and epidemiological studies but is time-consuming and methodologically
      challenging. We compared typing results obtained using a commercial repetitive
      element PCR (rep-PCR) system with PFGE in a sample of 86 unique MRSA isolates
      recovered from subjects in an academic referral hospital and two nursing homes in
      the same geographic region. Both methods reliably assigned isolates to the same
      Centers for Disease Control and Prevention (CDC) pulsotype. PFGE was
      significantly more discriminatory (Simpson's index of diversity, 0.92 at the 95%
      strain similarity threshold) than the commercial rep-PCR system (Simpson's index
      of diversity, 0.58). The global (adjusted Rand coefficient, 0.10) and directional
      congruence (adjusted Wallace coefficient(repPCR->PFGE) = 0.06; adjusted Wallace
      coefficient(PFGE -> repPCR) = 0.52) between the two methods was low. MRSA strains
      recovered from study nursing homes that were clonal when typed by the commercial
      rep-PCR method were frequently noted to be genetically distinct when typed using
      PFGE. These data suggest that the commercial rep-PCR has less utility than PFGE
      in small-scale epidemiological assessments of MRSA in health care settings.

PMID- 24671803
TI  - [Patients selection and response evaluation in neoadjuvant chemoradiation of
      rectal cancer].
AB  - Neoadjuvant chemoradiation combined with radical surgery has been established as
      the standard care for locally advanced rectal cancer(T3-T4 and/or N1-N2).
      Approximately 20% patients who achieve complete pathological response have an
      improved prognosis. Appropriate patient selection may help avoid over-treatment.
      Evaluation of treatment response mostly with imaging study and pathology after
      neoadjuvant chemoradiation and following surgery is essential for the subsequent
      selection of treatment strategy. 

PMID- 24671804
TI  - [Sensitive biomarkers of preoperative radiotherapy in advanced rectal cancer
      patients].
AB  - Preoperative radiotherapy represents the standard treatment for patients with
      locally advanced rectal cancer. Unfortunately, the response of individual tumors
      to multimodal treatment is heterogeneous and ranges from complete response to
      complete resistance. This poses a particular problem for patients with a prior
      resistant tumors because they may be exposed to irradiation, treatment regimens
      that are both expensive and at times toxic, without benefit. Accordingly, there
      is a strong need to establish molecular biomarkers that predict the response.
      Such biomarkers may guide clinicians in choosing the best possible treatment for
      each individual patient. It is vital to differentiate the molecular biomarkers to
      deal with the problem. This review summarized the advances in the biomarkers for
      response to preoperative radiotherapy for rectal cancer. 

PMID- 24671802
TI  - Path to clinical transplantation tolerance and prevention of graft-versus-host
      disease.
AB  - Although organ and bone marrow transplantations are life-saving procedures for
      patients with terminal diseases, the requirement for the lifelong use of
      immunosuppressive drugs to prevent organ graft rejection and the development of
      graft versus host disease (GVHD) remain important problems. Experimental
      approaches to solve these problems, first in preclinical models and then in
      clinical studies, developed at Stanford during the past 40 years are summarized
      in this article. The approaches use fractionated radiation of the lymphoid
      tissues, a procedure initially developed to treat Hodgkin's disease, to alter the
      immune system such that tolerance to organ transplants can be achieved and GVHD
      can be prevented after the establishment of chimerism. In both instances, the
      desired goal was achieved when the balance of immune cells was changed to favor
      regulatory innate and adaptive immune cells that suppress the conventional immune
      cells that ordinarily promote inflammation and tissue injury.

PMID- 24671805
TI  - [Intraoperative radiotherapy for rectal cancer].
AB  - Radiotherapy, surgery and chemotherapy are the main treatments for cancer. Though
      intraoperative radiotherapy(IORT) for rectal cancer is still at its preliminary
      stage in China, patients can get more benefits from IORT than pre- or post
      operative radiotherapy. IORT improves local control for locally advanced rectal
      cancer and improves overall survival rate of locally recurrent rectal cancer. In
      general, IORT is safe and feasible. It will be widely used for patients with
      rectal cancer in the future. 

PMID- 24671806
TI  - [Imaging diagnosis of perianal fistula in Crohn disease].
AB  - Anal fistula is the most common perianal lesion in Crohn disease (CD), which
      usually is complicated and difficult to treat, and has a high recurrence rate and
      serious influence on the quality of life of patients. Inaccurate or incomplete
      intervention may result in irreversible damage. In order to achieve the best
      outcome, an optimal disease assessment is crucial. Many imaging modalities are
      useful for the evaluation of perianal fistulas in CD, which may help confirm the
      diagnosis, accurately classify the disease, plan the most suitable treatment, and
      monitor the efficacy. Magnetic resonance imaging (MRI), endoscopic
      ultrasonography (EUS) and anal endosonography (AES) are considered to be the
      suitable options for evaluation of the initial perianal fistula, both in terms of
      sensitivity and specificity, while MRI is more suitable for monitoring the
      curative efficacy. Fistulography (by X ray or CT) is generally less applied due
      to inferior soft tissue performance, radiation exposure, etc. This paper reviews
      the various imaging modalities, analyzes their advantages and disadvantages in
      order to assist clinicians in selecting the most appropriate examination
      individually. 

PMID- 24671807
TI  - [Feasibility study on Xelox (capecitabine plus oxapliplatin) in the volumetric
      modulated arc therapy (VMAT)-based preoperative chemoradiotherapy for locally
      advanced rectal cancer].
AB  - OBJECTIVE: To investigate the feasibility of Xelox(capecitabine plus oxaliplatin)
      in the volumetric modulated arc therapy(VMAT)-based preoperative
      chemoradiotherapy (CRT) for locally advanced rectal cancer(LARC). METHODS:
      Clinical data of 141 LARC patients in our hospital from April 2011 to April 2013
      treated by preoperative CRT based on VMAT with concurrent Xelox followed by
      surgery were analyzed retrospectively. There were 95 men and 46 women, and the
      median age was 56 years old. Clinical staging was stage II( in 33 cases(18 cases
      with II(a, 11 cases with II(b, 4 cases with II(c) and stage III( in 108 cases(1
      case with III(a, 52 cases with III(b, 55 cases with III(c). The target doses were
      50 Gy for PTV1 in 25 fractions and 46 Gy for PTV2 in 23 fractions. RESULTS: All
      the patients completed the planned radiotherapy, and only 2 cases were
      interrupted with acute grade 3 diarrhea. The overall incidence of grade 3
      hematologic and non-hematologic adverse events during CRT was 9.9% and 16.3%
      respectively without grade 4 toxicity. Operation was performed after a median
      interval of 54 days(34-86 days) following CRT. The R0 resection rate was 100%,
      sphincter preservation rate for low rectal cancer was 45.8%(33/72), postoperative
      complication morbidity was 17.0%(24/141), pCR rate was 32.6%(46/141), and rates
      of pathological down-staging for the primary tumor, lymph node and clinical stage
      were 87.2%, 88% and 90.1%, respectively. CONCLUSIONS: Xelox is feasible and well
      tolerated in the treatment of VMAT-based preoperative CRT for patients with LARC,
      with excellent rates of pCR and pathological down-staging.

PMID- 24671808
TI  - [Diagnostic value of magnetic resonance diffusion weighted imaging for metastatic
      lymph nodes in patients with gastric cancer].
AB  - OBJECTIVE: To explore the preoperative diagnostic value of MR diffusion weighted
      imaging (DWI) for metastatic lymph nodes in patients with gastric cancer.
      METHODS: Between December 2011 and December 2012, 52 gastric cancer patients(34
      men, 18 women) underwent preoperative MR DWI. The apparent diffusion
      coefficient(ADC) and short diameter of lymph nodes were measured and compared
      with the postoperative histopathological findings. Diagnostic value of ADC and
      short diameter for metastatic lymph nodes in patients with gastric cancer was
      investigated by receiver characteristic curve(ROC) analysis. RESULTS: A total of
      180 metastatic and 57 non-metastatic lymph nodes were detected as hyperintense on
      DWI obtained from 52 patients. The ADC of metastatic lymph nodes [(1.059+/
      0.196)*10(-3) mm(2)/s] was significantly lower than that of non-metastatic nodes
      [(1.402+/-0.285)*10(-3) mm(2)/s, P<0.001]. With ADC threshold of 1.189*10(-3)
      mm(2)/s, the sensitivity, specificity and area under the curve(AUC) were 78.9%,
      72.8% and 0.840, respectively. The overall diagnostic accuracy of preoperative N
      staging of ADC was 75%(39/52). The short diameter of metastatic lymph nodes
      [(8.08+/-3.99) mm] was significantly longer than that of non-metastatic lymph
      nodes [(6.75+/-2.70) mm, P=0.005]. With short diameter threshold of 5.05 mm, the
      sensitivity, specificity and AUC were 88.3%, 29.8% and 0.602, respectively. The
      overall diagnostic accuracy of short diameter in preoperative N staging was
      67.3%(35/52). CONCLUSIONS: MR DWI is a useful technique in diagnosing metastatic
      lymph nodes in patients with gastric cancer. ADC value and short diameter can be
      used as diagnostic criterion for the diagnosis of preoperative N staging.

PMID- 24671809
TI  - [Comprehensive application of CT and PET/CT in diagnosing colorectal mucinous and
      non-mucinous adenocarcinoma].
AB  - OBJECTIVE: To explore the value of comprehensive application of CT and PET/CT in
      differential diagnosing mucinous and non-mucinous colorectal adenocarcinoma.
      METHODS: CT and PET/CT image data of 37 patients with mucinous adenocarcinoma and
      50 patients with non-mucinous adenocarcinoma confirmed by pathology in our
      hospital from January 2010 to December 2012 were analyzed retrospectively.
      Differences of image were compared between two methods. RESULTS: On CT, lesion
      density of pre-contrast, pro-contrast phase and enhancement degree were
      significantly lower in mucinous adenocarcinoma than those in non-mucinous
      adenocarcinoma(all P<0.01). Enhancement degree of hypointense area, hypointense
      area proportion of total lesion, and lymphatic or distant metastasis ratio were
      significantly higher in mucinous adenocarcinoma than those in non-mucinous
      adenocarcinoma(all P<0.05). On PET/CT, maximal SUV value of mucinous
      adenocarcinoma was significantly lower as compared to non-mucinous
      adenocarcinoma[(8.64+/-4.34) Bq/L vs. (12.38+/-5.96) Bq/L, P=0.015]. CONCLUSIONS:
      CT combined with PET/CT provides better valuable information in differential
      diagnosing between mucinous and non-mucinous colorectal adenocarcinoma and
      clinical practice.

PMID- 24671810
TI  - [Anatomy of the anal canal and staging of low rectal cancer with high resolution
      magnetic resonance imaging].
AB  - OBJECTIVE: To evaluate high resolution MR in imaging of the anatomy and tumor
      invasion of the anal canal. METHODS: Twenty-three patients with low rectal cancer
      confirmed by pathology results were recruited as the study group and 20 patients
      without history of anal canal diseases were recruited as the control group. All
      patients received MRI examinations containing three TSE-T2WI sequences and three
      3D-VIBE sequences. The distance between the tumor and the anal margin was
      measured in the study group. Two radiologists finished T staging of the tumor
      independently. RESULTS: MRI had a clear demonstration of the anatomy of the anal
      canal in all 20 control patients. The T staging of 23 patients of study group was
      T2 (n=8), T3 (n=7), and T4 (n=8), and the depth of anal canal invasion (T-DACI)
      was T0-DACI (n=10), T1-DACI (n=1), T2a-DACI (n=3), T2-DACI (n=3), T3-DACI (n=4)
      and T4-DACI (n=2). Eight patients received surgery and the consistency between
      pathological staging and imaging staging was 75%. CONCLUSION: High resolution MRI
      has the capacity of demonstrating the complex anatomy of the anal canal, and can
      provide evidence of anal canal invasion for low rectal cancer.

PMID- 24671812
TI  - [Preoperative T staging of gastric cancer: comparison between MR including
      diffusion weighted imaging and contrast enhanced CT scan].
AB  - OBJECTIVE: To compare the accuracy of CT and MR including diffusion-weighted
      imaging(DWI) in preoperative diagnosis and T staging of gastric cancer. METHODS:
      Forty-one patients with gastric cancers proved by gastroscopy biopsy from
      November 2011 to August 2012 were prospectively enrolled. They underwent contrast
      enhanced CT and MR imaging (including DWI, T2 weighted and dynamic enhanced
      imaging) preoperatively. Two radiologists interpreted CT and MR images for
      detecting and staging each patient independently. With the reference of post
      operative histopathological findings, T staging accuracy of CT and MR imaging was
      calculated and compared. Inter-observer agreement was also evaluated. RESULTS:
      Overall T staging accuracy in MR including DWI was significantly higher than that
      in CT imaging(87.8% vs. 65.9%, P=0.004). MR had a better inter-observer agreement
      than CT(Kappa=0.813, 0.603, respectively). CONCLUSION: MR including DWI can
      improve preoperative T staging accuracy of gastric cancer significantly, which
      deserves recommendation for clinical application.

PMID- 24671811
TI  - [Diagnostic value of water enema (18)F-fluorodexyglucose positron emission
      tomography and computed tomography in incidental finding of hypermetabolism focus
      in the colorectum].
AB  - OBJECTIVE: To investigate the value of water enema (18)F-fluorodexyglucose
      positron emission tomography and computed tomography((18)F-FDG PET-CT) in
      incidental finding of hypermetabolism focus in the colon and rectum for
      differential diagnosis of benign or malignant lesions. METHODS: From June 2010 to
      December 2012 in our hospital, 77 patients were found incidentally with uncertain
      hypermetabolism focuses in the colon and rectum during PET-CT examination. Water
      enema (18)F-FDG PET-CT was performed to classify the lesions. According to the
      pathological examination and clinical follow-up, these cases were divided into
      malignant disease (including advanced colorectal adenoma), benign adenoma,
      inflammation and physiological uptake. Radioactive uptake level (SUVmax) and
      change of water enema imaging (retention index, RI) of hypermetabolism focus were
      compared between groups. RESULT: Of these 77 cases, 23 were malignant diseases,
      16 benign adenoma, 7 inflammation and 31 physiological uptake. The difference of
      average SUVmax was not statistically significant between benign and malignant
      lesions as well as physiological uptake(P>0.05). But the difference of RI was
      statistically significant between neoplastic lesions and inflammation(P<0.05).
      The accuracy of water enema (18)F-FDG PET-CT in diagnosing non-neoplastic uptake
      was 100%, and the sensitivity, specificity and accuracy in differentiation of
      malignancy form benign lesions were 95.6%, 96.3%, and 96.1% respectively.
      CONCLUSIONS: The incidental focal colorectal (18)F-FDG uptake in PET-CT may
      indicate potential colorectal malignant lesions and adenoma. Water enema can
      effectively differentiate the physiological uptake and predict benign lesions or
      malignancy in the colon and rectum colorectum with good accuracy.

PMID- 24671813
TI  - [Evaluation of sphincter damage degree with anal endosonography for children with
      fecal incontinence].
AB  - OBJECTIVE: To evaluate the application of anal endosonography in the morphology
      of internal anal sphincter (IAS), external anal sphincter (EAS) and puborectalis
      (PR) in order to provide necessary information for analysis of the etiology of
      fecal incontinence and formulation of the therapeutic schedule. METHODS: From
      December 2010 to November 2012, 18 children of anorectal malformation (n=14) or
      Hirschsprung's disease(n=4) with fecal incontinence received anal endosonography.
      The morphology of IAS, EAS and PR was observed. The damage of anal sphincter was
      classified according to Starck criteria. Anorectal mamometry and anal clinical
      score were measured simultaneously. Spearman analysis was performed to examine
      the correlation of anal sphincter damage with anorectal mamometric score and anal
      clinical score. RESULTS: According to Starck criteria, anal sphincter damage was
      small in 11 children, moderate in 6, and severe in 1. PR damage was found in 4
      cases. Starck score was positively correlated with manometric score(P<0.05),
      while not correlated with anal clinical score(P>0.05). CONCLUSIONS: Anal
      endosonography can clearly display the morphology of IAS, EAS and PR, and their
      integrity and damage degree. It is a very valuable technique to evaluate the anal
      sphincter of the children with fecal incontinence, which however can not reflect
      the function of anal sphincter and anal continence thoroughly.

PMID- 24671814
TI  - [Diagnostic value of contrast-enhanced ultrasonography in preoperative Borrmann
      classification of gastric cancer].
AB  - OBJECTIVE: To investigate the diagnostic value of contrast-enhanced
      ultrasonography (CEUS) in preoperative Borrmann classification of gastric cancer.
      METHODS: Asulfur hexafluonde-filled microbubble ultrasound contrast agent and
      continuous real-time imaging technique of contrast pulse sequencing were used.
      Two hundred and eighty-five patients with gastric cancer confirmed by biopsies
      who received preoperative CEUS examination were involved in this study. CEUS
      results were compared with postoperative pathological findings. RESULTS: The
      accuracy rate of CEUS in determining the Borrmann classification of gastric
      cancer was 92.3%(263/285). The accuracy rates of BorrmannI(, II(, III(, IIII(,
      and IIIII( were 100%(12/12), 90.6%(77/85), 92.6%(126/136), 95.7%(45/47), and
      60.0%(3/5) respectively. CONCLUSION: CEUS is a useful diagnostic method for
      preoperative Borrmann classification of gastric cancer.

PMID- 24671815
TI  - [Meta-analysis of diagnostic accuracy of magnetic resonance in restaging of
      rectal cancer after preoperative chemoradiotherapy].
AB  - OBJECTIVE: To estimate the diagnostic accuracy of magnetic resonance(MR) in
      restaging of rectal cancer after preoperative chemoradiotherapy(CRT). METHODS:
      Comprehensive search of literature concerning the diagnosis of MR for rectal
      cancer after preoperative CRT was performed from databases of PubMed, EMbase,
      OVID and WOK. Sensitivity and specificity of MR on restaging of rectal cancer
      after preoperative CRT were investigated by SAS and MetaDiSc software. RESULTS:
      Thirteen articles including 749 patients were enrolled in this meta-analysis. For
      T3-T4 stage, sensitivity of MR was 82.1%(95%CI:67.9%-90.9%), specificity was
      53.5%(95%CI:39.3%-67.3%), and diagnostic odds ratio(DOR) was 5.34(2.73, 6.59).
      For lymph node involvement, sensitivity of MR was 61.8%(95%CI:50.7%-71.8%),
      specificity was 72.0%(95%CI:61.3%-80.7%), and DOR was 4.33(95%CI:2.84-6.59). For
      circumferential resection margin(CRM) by MR, pooled sensitivity was
      85.4%(95%CI:60.5%-95.7%), specificity was 80.0%(95%CI:57.4%-92.3%), and DOR was
      27.62(95%CI:13.03-58.55). CONCLUSIONS: Restaging accuracy of T3-T4 and lymph
      nodes involvement of rectal cancer after preoperative CRT by MR is not high. MR
      may be a good method to make reassessment of CRM. To avoid overtreatment for T0
      T2, negative lymph node and circumferential resection of rectal cancer, restaging
      by MR after preoperative CRT is important.

PMID- 24671816
TI  - [CT angiography features of the involved arterial branches of the spontaneous
      isolated superior mesenteric artery dissection].
AB  - OBJECTIVE: To explore the CT angiography features of the involved arterial
      branches of the spontaneous isolated superior mesentery artery
      dissection(SISMAD). METHODS: Clinical and CT angiogram data of 6 patients with
      SISMAD confirmed by dual source energy CT angiography were analyzed
      retrospectively. The CT angiography features and prognosis of patients were
      investigated. RESULTS: Average age of 6 patients was(45.83+/-5.60) years old. Ten
      branches of jejunoileal artery were involved in 4 patients. All the dissections
      of the superior mesenteric arteries(SMA) were extended from its proximal to its
      end. Intramural hematoma was found in all the involved branches, which showed
      eccentric target sign in the transverse section and sandwich sign in the
      longitudinal axial section. In 7 branches of 3 patients, the involved branches
      originated from the false lumina of the SMA. In one patient, the intramural
      hematoma of the jejunoileal arteries was found to be completely absorbed in a
      repeated CT angiography one year late. CONCLUSIONS: For the SISMAD, the
      involvement of the branches of the SMA may be associated with the extension of
      the dissection of the SMA. The inflation of the false lumina of the branches is
      worse than that of the SMA. With the improvement of the dissection of the SMA,
      the intramural hematoma of the branches can be absorbed. The conservative
      treatment may be the first choice for SISMAD without emergency.

PMID- 24671817
TI  - [Clinical analysis of laparoscopic complete mesocolic excision in right
      colectomy].
AB  - OBJECTIVE: To investigate the application and short-term efficacy of laparoscopic
      complete mesocolic excision in right colectomy. METHODS: The data of continuous
      70 cases of ascending colon cancer enrolled in the Peking University Cancer
      Hospital and Institute between April, 2009 and November, 2011 were analyzed
      retrospectively. RESULTS: A total of 65 cases received laparoscopic CME procedure
      and were enrolled in the final analysis. The median number of lymph nodes
      retrieved was 24, the median operation time was 185 min, the median blood loss
      was 50 ml. The overall postoperative complication rate was 9.2%(6/65), and the
      median time of first flatus and post-operative hospital stay was 3 days and 7
      days respectively. The median 30-day hospital readmission and postoperative death
      were not found. The 2-years overall survival rate and disease-free survival rate
      were 98.5% and 83.1% respectively. CONCLUSIONS: Laparoscopic complete mesocolic
      excision in right colectomy is feasible and do not give patients extra burden.
      The short-term follow up reveals good efficacy.

PMID- 24671818
TI  - [Clinical efficacy of tissue adhesive on intractable bleeding during endoscopic
      submucosal dissection].
AB  - OBJECTIVE: To investigate the efficacy of tissue adhesive on intractable bleeding
      during endoscopic submucosal dissection(ESD) and delayed bleeding. METHODS: A
      total of 9874 patients with gastrointestinal mucosal or submucosal tumors
      underwent ESD in our center from September 2006 to August 2013 and intractable
      bleeding occurred during ESD in 5 cases. Under the condition of no effective
      hemostasis methods, the tissue adhesive injection or spray were used to stop the
      bleeding. The efficacy and safety were evaluated. RESULTS: All the 5 cases were
      successfully managed by the hemostasis method with tissue adhesive without any
      adverse event. In follow-up of two months after operation, wound healing and scar
      formation were observed under endoscopy. CONCLUSION: Tissue adhesive is safe,
      effective and fast for intractable bleeding during ESD and delayed bleeding.

PMID- 24671819
TI  - [Role of the small intestinal decompression tube and Gastrografin in the
      treatment of early postoperative inflammatory small bowel obstruction].
AB  - OBJECTIVE: To evaluate the role of the small intestinal decompression tube (SIDT)
      and Gastrografin in the treatment of early postoperative inflammatory small bowel
      obstruction (EPISBO). METHODS: Twelve patients presented EPISBO after abdominal
      surgery in our department from April 2011 to July 2012. Initially, nasogastric
      tube decompression and other conventional conservative treatment were
      administrated. After 14 days, obstruction symptom improvement was not obvious,
      then the SIDT was used. At the same time, Gastrografin was injected into the
      small bowel through the SIDT in order to demonstrate the site of obstruction of
      small bowel and its efficacy. RESULTS: In 11 patients after this management,
      obstruction symptoms disappeared, bowel function recovered within 3 weeks, and
      oral feeding occurred gradually. Another patient did not pass flatus after 4
      weeks and was reoperated. After postoperative follow-up of 6 months, no case
      relapsed with intestinal obstruction. CONCLUSION: For severe and long course of
      early postoperative inflammatory intestinal obstruction, intestinal decompression
      tube plus Gastrografin is safe and effective, and can avoid unnecessary
      reoperation.

PMID- 24671820
TI  - [Cell morphology in the dormancy and proliferation stage of colorectal cancer
      stem cells].
AB  - OBJECTIVE: To study the cell morphology change in dormancy and proliferation
      stage of colorectal cancer stem cells in order to provide reference to the
      treatment of colorectal cancer. METHODS: The subpopulation of
      EpCAM(high)/CD44(+)/CD133(+) was isolated from fresh colorectal cancer tissues.
      These cells were tested by xenograft assay in NOD/SCID nude mice. Colorectal
      cancer stem cells underwent three-dimensional culture, and the growth curve of
      stem cells was drawn by WST-1. The expression of P27 and Ki-67 was examined by
      flow cytometry to understand the phase of dormancy and proliferation of
      colorectal cancer stem cells. Then the morphological differences of colorectal
      cancer stem cells between dormant and proliferation stages were recognized by
      immunofluorescence staining of actin. RESULTS: The percentage of
      EpCAM(high)/CD44(+)/CD133(+) was 1.6%, and the subpopulation was confirmed to be
      colorectal cancer stem cells by means of the experiment of tumorigenicity in
      vivo. The growth curve of colorectal cancer stem cells was "S" type. Colorectal
      cancer stem cells grew slowly in the first three days. The expression of P27 was
      gradually up-regulated, and the level of Ki-67 was very low. These cells remained
      quiescence, which was the so-called dormancy. The expression of Ki-67 of
      colorectal cancer stem cells was at high level since the fourth day, and the P27
      level was very low. According to the growth curve, this period belonged to the
      proliferative stage of colorectal cancer stem cells. On immunofluorescence
      staining, colorectal cancer stem cells with high level of P27 were round, large,
      and few pseudopodium, but no obvious death was found. These cells showed
      characteristics of dormancy. In contrast, the stem cells with high level of Ki-67
      had much pseudopodium, showing proliferation and invasion. CONCLUSIONS: Cancer
      recurrence and metastasis may be associated with the change of growth state of
      cancer stem cells. Colorectal cancer stem cells in the proliferation stage show
      greater proliferative and invasive ability as compared to the dormancy stage,
      which provides a new perspective for the treatment of colorectal cancer, and
      recurrence and metastasis of other tumors.

PMID- 24671821
TI  - [Application of sacral nerve stimulation in patients with fecal incontinence].
AB  - Fecal incontinence is one of diseases effecting the quality of life and mental
      health. Germany surgeon used sacral nerve stimulation(SNS) to treat fecal
      incontinence at first in 1995. The aim of SNS is to mobilize the ability to
      control the feces through stimulating the nerves of dominating the sphincter
      muscles and pelvic floor muscles. Standard SNS includes two stages: evaluation
      stage of SNS and permanent implantation stage. Preoperative evaluation plays
      important role in guaranteeing the success of treatment. SNS is the primary
      treatment of choice for severe fecal incontinence. The complications of SNS
      include pain, shift of electronic probe, wound dehiscence, bowel dysfunction and
      infection. 

PMID- 24671822
TI  - High serum carbohydrate antigen 125 concentration can predict serous effusion but
      not gastrointestinal malignancy in male patients.
AB  - This study aims to evaluate the diagnostic accuracy of carbohydrate antigen 125
      (CA125) in male patients for predicting gastrointestinal malignant diseases. One
      hundred twenty consecutive male patients underwent CA125 test after admission to
      the Department of Gastroenterology in Changhai Hospital, the Second Military
      Medical University, from April to June 2013. Data of age, main symptoms, and
      final diagnosis were summarized. The sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), positive likelihood
      ratio (PLR), and negative likelihood ratio (NLR) of CA125 for malignancy were
      estimated, and the receiver operating characteristic (ROC) analysis and the area
      under the curve (AUC) were also performed to evaluate the diagnostic value of
      CA125 in male patients. The PPV, NPV, PLR, and NLR of CA125 in malignancy were 55
      %, 69 %, 1.90, and 0.71, respectively. However, we found that an elevated serum
      CA125 level was more common in male patients with serous effusion than those with
      malignancy. The PPV, NPV, PLR, and NLR of CA125 in serous effusion were 85 %, 96
      %, 12.70, and 0.09, respectively. In the ROC analysis, the AUC values for CA125
      was 0.96 (95 % confidence interval, 0.93-0.99) for discriminating patients with
      serous cavity effusion from those without serous effusion. CA125 has a higher
      accuracy in detecting serous effusion than malignancy in male patients with
      gastrointestinal diseases. It is of little significance for male patients to
      perform CA125 test for malignancy.

PMID- 24671823
TI  - VPAC1 overexpression is associated with poor differentiation in colon cancer.
AB  - Vasoactive intestinal peptide (VIP) is a neurotransmitter that primarily
      functions as a vasodilator. VIP plays its role through binding to its receptors
      known as VIP/pituitary adenylate cyclase-activating peptide receptors (VPACs). In
      this study, we examined the expression of VPAC1 in human colon cancer tissues,
      analyzed the relationship between VPAC1 expression and cancer malignancy, and
      explored the possible mechanisms using immunohistochemistry and
      immunofluorescence double staining. The results showed that (1) poorly
      differentiated colon cancers have significantly higher VPAC1 expression than well
      differentiated colon cancers do (p < 0.01); (2) phospho-epithelial growth factor
      receptor (EGFR) overexpression/activation in the cytoplasm of cancer cells is
      related to VPAC1 overexpression; (3) blood vessels surrounding colon cancer have
      significantly more VPAC1-positive than normal colon mucosa does; (4) tumor
      associated macrophages (TAMs) of colon cancer have a higher level of VPAC1
      expression than macrophages in normal colon mucosa do. These data suggest that
      VPAC1 overexpression is associated with poorer differentiation of colon cancer,
      which is likely caused by subsequent EGFR activation in cancer cells. In
      addition, VPAC1 overexpression in both blood vessels and macrophages in tumors
      may also play an important role in the development of aggressive cancer.

PMID- 24671825
TI  - Canada's progress toward an orphan drug framework: 2014.

PMID- 24671824
TI  - Lack of association between interferon gamma +874 T/A polymorphism and cancer
      risk: an updated meta-analysis.
AB  - Interferon gamma (IFN-gamma) is a potent proinflammatory cytokine which plays a
      pivotal role in the antiviral, antiproliferative, and antitumor activities. A T
      to-A transition at the position +874 of human IFN-gamma gene (IFNG) has been
      reported to influence the secretion of IFN-gamma and affect cancer
      susceptibility. However, results from published studies on the association
      between IFNG +874 T/A polymorphism and cancer risk are inconclusive or even
      controversial. In order to derive a more precise estimation of the association, a
      meta-analysis of 38 eligible studies including 5,630 cases and 6,096 controls was
      conducted with odds ratio (OR) and its corresponding 95 % confidence interval (95
      % CI). Overall, no significant association was detected in allelic model (A
      allele vs. T allele-OR = 0.96, 95 % CI, 0.86-1.08), homozygote comparison (AA vs.
      TT-OR = 0.97, 95 % CI, 0.79-1.21), heterozygote comparison (AT vs. TT-OR = 1.03,
      95 % CI, 0.87-1.23), dominant model (AA + AT vs. TT-OR = 1.00, 95 % CI, 0.87
      1.15), nor recessive model (AA vs. AT + TT-OR = 0.93, 95 % CI, 0.78-1.12).
      Further subgroup analyses based on ethnicity, cancer types, and Hardy-Weinberg
      equilibrium status failed to demonstrate any significant relationship except in
      African population under recessive model (AA vs. AT + TT-OR = 0.68, 95 % CI, 0.47
      0.97). In conclusion, the current meta-analysis suggested that IFNG +874 T/A
      polymorphism may not contribute to cancer susceptibility, and further well
      designed studies with large sample size are warranted to validate our conclusion.

PMID- 24671826
TI  - A MATLAB toolbox for the efficient estimation of the psychometric function using
      the updated maximum-likelihood adaptive procedure.
AB  - A MATLAB toolbox for the efficient estimation of the threshold, slope, and lapse
      rate of the psychometric function is described. The toolbox enables the efficient
      implementation of the updated maximum-likelihood (UML) procedure. The toolbox
      uses an object-oriented architecture for organizing the experimental variables
      and computational algorithms, which provides experimenters with flexibility in
      experimental design and data management. Descriptions of the UML procedure and
      the UML Toolbox are provided, followed by toolbox use examples. Finally,
      guidelines and recommendations of parameter configurations are given. 

PMID- 24671827
TI  - GraFIX: a semiautomatic approach for parsing low- and high-quality eye-tracking
      data.
AB  - Fixation durations (FD) have been used widely as a measurement of information
      processing and attention. However, issues like data quality can seriously
      influence the accuracy of the fixation detection methods and, thus, affect the
      validity of our results (Holmqvist, Nystrom, & Mulvey, 2012). This is crucial
      when studying special populations such as infants, where common issues with
      testing (e.g., high degree of movement, unreliable eye detection, low spatial
      precision) result in highly variable data quality and render existing FD
      detection approaches highly time consuming (hand-coding) or imprecise (automatic
      detection). To address this problem, we present GraFIX, a novel semiautomatic
      method consisting of a two-step process in which eye-tracking data is initially
      parsed by using velocity-based algorithms whose input parameters are adapted by
      the user and then manipulated using the graphical interface, allowing accurate
      and rapid adjustments of the algorithms' outcome. The present algorithms (1)
      smooth the raw data, (2) interpolate missing data points, and (3) apply a number
      of criteria to automatically evaluate and remove artifactual fixations. The input
      parameters (e.g., velocity threshold, interpolation latency) can be easily
      manually adapted to fit each participant. Furthermore, the present application
      includes visualization tools that facilitate the manual coding of fixations. We
      assessed this method by performing an intercoder reliability analysis in two
      groups of infants presenting low- and high-quality data and compared it with
      previous methods. Results revealed that our two-step approach with adaptable FD
      detection criteria gives rise to more reliable and stable measures in low- and
      high-quality data. 

PMID- 24671828
TI  - Short- and long-term effects of litter size manipulation in a small wild-derived
      rodent.
AB  - Iteroparous organisms maximize their overall fitness by optimizing their
      reproductive effort over multiple reproductive events. Hence, changes in
      reproductive effort are expected to have both short- and long-term consequences
      on parents and their offspring. In laboratory rodents, manipulation of
      reproductive efforts during lactation has however revealed few short-term
      reproductive adjustments, suggesting that female laboratory rodents express
      maximal rather than optimal levels of reproductive investment as observed in
      semelparous organisms. Using a litter size manipulation (LSM) experiment in a
      small wild-derived rodent (the common vole; Microtus arvalis), we show that
      females altered their reproductive efforts in response to LSM, with females
      having higher metabolic rates and showing alternative body mass dynamics when
      rearing an enlarged rather than reduced litter. Those differences in female
      reproductive effort were nonetheless insufficient to fully match their pups'
      energy demand, pups being lighter at weaning in enlarged litters. Interestingly,
      female reproductive effort changes had long-term consequences, with females that
      had previously reared an enlarged litter being lighter at the birth of their
      subsequent litter and producing lower quality pups. We discuss the significance
      of using wild-derived animals in studies of reproductive effort optimization.

PMID- 24671829
TI  - Can male Eurasian jays disengage from their own current desire to feed the female
      what she wants?
AB  - Humans' predictions of another person's behaviour are regularly influenced by
      what they themselves might know or want. In a previous study, we found that male
      Eurasian jays (Garrulus glandarius) could cater for their female partner's
      current desire when sharing food with her. Here, we tested the extent to which
      the males' decisions are influenced by their own current desire. When the males'
      and female's desires matched, males correctly shared the food that was desired by
      both. When the female's desire differed from their own, the males' decisions were
      not entirely driven by their own desires, suggesting that males also took the
      female's desire into account. Thus, the male jays' decisions about their mates'
      desires are partially biased by their own desire and might be based upon similar
      processes as those found in humans. 

PMID- 24671830
TI  - The adaptive function of melanin-based plumage coloration to trace metals.
AB  - Trace metals produced by anthropogenic activities are of major importance in
      urban areas and might constitute a new evolutionary force selecting for the
      ability to cope with their deleterious effects. Interestingly, melanin pigments
      are known to bind metal ions, thereby potentially sequestering them in inert body
      parts such as coat and feathers, and facilitating body detoxification. Thus, a
      more melanic plumage or coat coloration could bring a selective advantage for
      animals living in polluted areas. We tested this hypothesis by investigating the
      link between melanin-based coloration and zinc and lead concentrations in
      feathers of urban feral pigeons, both at capture time and after one year of
      captivity in standardized conditions. Results show that differently coloured
      pigeons had similar metal concentrations at capture time. Metal concentrations
      strongly decreased after one year in standardized conditions, and more melanic
      pigeons had higher concentrations of zinc (but not lead) in their feathers. This
      suggests that more melanic pigeons have a higher ability to store some metals in
      their feathers compared with their paler counterparts, which could explain their
      higher success in urbanized areas. Overall, this work suggests that trace metal
      pollution may exert new selective forces favouring more melanic phenotypes in
      polluted environments. 

PMID- 24671833
TI  - An Orphan Drug Framework (ODF) for Canada.
AB  - An orphan drug is a pharmaceutical or biological drug that is used to treat a
      rare disease. The development of a Canadian orphan drug framework is intended to
      help translate scientific discoveries into meaningful results for Canadian rare
      disease patients. 

PMID- 24671834
TI  - [A postgraduate experience at the ASN's annual meeting].
AB  - The annual meeting of the American Society of Nephrology (ASN) is one of the most
      important conferences in this field. It has a high scientific quality and it
      receives thousands of participants from all over the world. In this paper, a
      fellow in Nephrology describes her attendance to this meeting. Moreover, two
      topics have been selected and summarized: the role of complement in the
      thrombotic microangiopathy and the autosomal dominant polycystic kidney disease. 

PMID- 24671831
TI  - Exploratory analysis of glyburide as a novel therapy for preventing brain
      swelling.
AB  - BACKGROUND: Malignant infarction is characterized by the formation of cerebral
      edema, and medical treatment is limited. Preclinical data suggest that glyburide,
      an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously
      reported feasibility of the GAMES-Pilot study, a two-center prospective, open
      label, phase IIa trial of 10 subjects at high risk for malignant infarction based
      on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127
      (glyburide for injection). In this secondary analysis, we tested the hypothesis
      that RP-1127 may be efficacious in preventing poor outcome when compared to
      controls. METHODS: Controls suffering large hemispheric infarction were obtained
      from the EPITHET and MMI-MRI studies. We first screened subjects for controls
      with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next,
      to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0
      4, rate of decompressive craniectomy, and mortality were the primary clinical
      outcomes of interest. RESULTS: The mean age of the GAMES cohort was 51 years and
      initial DWI volume was 102 +/- 23 cm(3). After Euclidean matching, GAMES subjects
      showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus
      50% in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43)
      and trend toward lower mortality (10 vs. 35%; p = 0.21). CONCLUSIONS: In this
      pilot study, RP-1127-treated subjects showed better clinical outcomes when
      compared to historical controls. An adequately powered and randomized phase II
      trial of patients at risk for malignant infarction is needed to evaluate the
      potential efficacy of RP-1127.

PMID- 24671832
TI  - Reversal of coagulopathy using prothrombin complex concentrates is associated
      with improved outcome compared to fresh frozen plasma in warfarin-associated
      intracranial hemorrhage.
AB  - BACKGROUND: There are no studies demonstrating that prothrombin complex
      concentrates (PCC) improves outcome compared FFP in patients with warfarin
      associated intracranial hemorrhage. METHODS: A prospective, observational study
      was conducted of patients who received PCC (Bebulin VH), FFP, or PCC + FFP. All
      groups received vitamin K 10 mg IV. INR reversal (<1.4), adverse events (venous
      thromboembolism, myocardial infraction, pulmonary edema), major hemorrhage (new
      or worsened intracranial hemorrhage, anemia requiring transfusion or GI bleed),
      and 3-month functional outcome were compared between the groups using Chi squared
      and logistic regression analysis. RESULTS: Of 64 patients, PCC alone was used in
      16 (mean dose 48 IU/kg), FFP alone in 25 (mean dose 12.5 ml/kg), and PCC + FFP in
      23 (median doses 47.4 IU/kg and 11.4 ml/kg, respectively). INR correction
      occurred in 88, 84, and 70 %, respectively. There were no differences in time to
      INR correction or adverse events between the groups, but FFP alone was associated
      with more major hemorrhage after administration (52 %, OR 5.0, 95 % CI 1.6-15.4,
      P = 0.006) and PCC with less (6 %, OR 0.1, 95 % CI 0.01-0.8, P = 0.033). After
      adjusting for age, admission GCS, initial INR, and bleed type, the use of PCC was
      associated with a lower risk of death or severe disability at 3-months (adjusted
      OR 0.02, 95 % CI 0.001-0.8, P = 0.039), while FFP alone was associated with a
      higher risk (adjusted OR 51.6, 95 % CI 1.2-2163.1, P = 0.039). CONCLUSIONS: PCC
      adequately corrected INR without any increase in adverse events compared to FFP
      and was associated with less major hemorrhage and improved 3-month outcomes in
      patients with warfarin-associated intracranial hemorrhage.

PMID- 24671835
TI  - [C3 glomerulopathy].
AB  - C3 glomerulopathy includes C3 glomerulonephritis, Dense Deposit Disease, Factor H
      Related Protein 5 (CFHR5) nephropathy and most atypical acute postinfectious
      glomerulonephritis. The characteristic of this nephropathy is C3 deposits without
      immunoglobulins. Light microscopy pattern can be mesangial proliferative or
      membrano-proliferative. A dysregulation of complement is at the base of the
      disease: acquired changes (autoantibodies anti-C3 convertase -C3 Nephritic Factor
      , anti-factor H, I or B) or genetic changes (mutations of factors B, H, I, or 1-5
      Factor H-related proteins) are found. Targeted treatments are directed towards
      replacement of lacking factors with plasma or to removal of antibodies with
      plasma exchange or towards control of complement functioning. In particular
      eculizumab, a humanized monoclonal antibody directed against C5, has been shown
      to have a favourable effect in anecdotal cases and in a small series of patients
      in a prospective study. Corticosteroids and immunosuppressive drugs are
      ineffective. Further studies on this nephropathy will define characteristics and
      indicate the most suitable treatment options. 

PMID- 24671836
TI  - [Spending review, personal view, water and waste in (home) hemodialysis].
AB  - In a moment of particular attention to the health care costs, of global crisis
      and of concerns not only for the economic future of our Society, but also for the
      precarious health of our Planet, it is worth reading an Australian article
      entitled Personal viewpoint: hemodialysis-water, power, and waste disposal:
      rethinking our environmental responsibilities, by Agar, one of the spokesman of
      the "ecological dialysis". The article describes, with some irony, some paradoxes
      of the ecological and economic costs of dialysis. Among these, 156 billion of
      liters of water per year and a minimum of 625000 tons of waste products, at least
      partly potentially reusable. With regards to his battle for a planet friendly
      dialysis, Agar comments that perseverance is not a diffused virtue. Keeping in
      mind the cost of waste disposal, reading this paper can be an invitation to an
      intelligent saving policy that directs attention to the economy and to the world
      around us. 

PMID- 24671837
TI  - [From hyponatremia to tolvaptan].
AB  - Hyponatremia is the electrolytic disorder that is observed most frequently in
      hospitalized patients. Itinfluences prognosis in the short, mid and long term.
      Although many cases are asymptomatic, hyponatremia can cause severe neurological
      symptoms, depending on the amount of serum sodium reduction and on the rapidity
      with which it occurs. Thus, treatment assumes crucial importance and must be
      accompanied by careful monitoring of urine output and serum sodium to prevent
      accelerated corrections and therefore the risk of osmotic demyelination syndrome.
      The various therapies have different indications according to the underlying
      cause of hyponatremia, the presence and severity of symptoms, the duration and
      degree of the electrolytic alteration. Over the last few years, the aquaretic
      agents and in particular tolvaptan have acquired great importance compared with
      the traditional therapeutic approaches (fluid restriction, 3% saline solution
      and, more rarely, demeclocycline, lithium and urea). In Europe, the oral
      tolvaptan has been commercialized only for the treatment of euvolemic
      hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic
      hormone).Conversely in the USA, intravenous conivaptan (V1a/V2 vasopressin
      receptor antagonist) and oral tolvaptan have been marketed for the treatment of
      both euvolemic and hypervolemic hyponatremia.Besides being effective drugs,
      aquaretics have the benefit of having drawn the attention of physicians against
      hyponatremia. Unlike infusion saline therapy or fluid restriction, aquaretics
      allow them to establish long-term therapies which, once started in a hospital
      setting for safety reasons, may be continued at the patient's home, still under
      close monitoring. 

PMID- 24671838
TI  - [Hemoperitoneum after drop-out from peritoneal dialysis].
AB  - A 55-years-old woman with end-stage renal disease presented on hemodialysis
      bloody ascitis after transfer from peritoneal dialysis. During the 8 years of
      peritoneal dialysis, she had exit-site infection and a culture-negative
      peritonitis. She was dropped-out of hemodialysis for ultrafiltration failure
      associated with "high" peritoneal transport. Clinic and radiologic findings was
      suggestive for the encapsulating peritoneal sclerosis, which was confirmed upon
      biopsy of the peritoneum. The patient was treated successfully with
      immunosuppressive. Our case is relevant, both because many clinical features that
      have been described must draw attention to the encapsulating peritoneal
      sclerosis, rare but life-threatening complication of peritoneal dialysis and
      because of its favorable outcome, unfortunately infrequent. 

PMID- 24671839
TI  - [Renal cysts: current indications for ultrasound study].
AB  - In order to optimize the use of ultrasound in the characterization of cystic or
      nodular lesions, the incidence of simple cysts in the general population, their
      growth and evolution is discussed considering some follow-up studies. After
      studying the typical sonographic criteria of simple cyst, we describe the
      sonographic features of cancer and the incidence of various types of tumors. In
      such cases radiological evaluations are required and the Bosniak classification
      is useful in the clinical choice of waiting, more detailed diagnosis or excision
      of the lesion. The use of the radiological means will decrease when
      EcocolorDoppler with contrast is widely available. Nevertheless, this technique
      has already found its way into peculiar fields and in certain cases, it has a
      higher sensitivity compared to TAC with contrast medium. 

PMID- 24671841
TI  - [Acute phosphate nephropathy (APN)].
AB  - Acute phosphate nephropathy (APN) is a clinical condition, appeared in the last
      decade, in patients under treatment with oral sodium phosphate bowel purgative
      (OSPS). Renal damage induced by OSPS may occur as acute or chronic disease. The
      former commonly appears within few hours after bowel cleansing with OSPS. It is
      clinically characterized by severe hyperphospatemia (4.519.4 mmol/l) and
      hypocalcemia (11.17mmol/l). Recovery of renal function may occur in some
      patients, while others develop chronic kidney disease (CKD), with possible
      evolution towards end-stage renal disease (ESRD). Renal biopsy reveals acute
      nephrocalcinosis characterized by abundant distal tubular calcium phosphate
      deposits, associated with tubular athrophy and interstitial fibrosis.
      Predisposing factors for the onset of APN include female sex, senescence,
      diabetes mellitus, arterial hypertension, CKD and use of diuretic or drugs acting
      on renin-angiotensin system (RAS). The diagnosis is suggested by the timely
      association between assumption of OSPS for bowel cleansing and acute kidney
      injury. However, chronic complications may remain unrecognized, without periodic
      control of renal function after OSPS assumption.Most importantly, the definitive
      diagnosis needs to be confirmed by renal biopsy. In 2006, FDA published an alert,
      recommending caution in the use of OSPS in patients with impaired renal function.

PMID- 24671840
TI  - [Oral hypoglycemic drugs in chronic kidney disease: which limitations in the
      clinical setting].
AB  - A large amount of recent epidemiological studies have shown the worldwide growth
      on the incidence and prevalence of diabetes mellitus type II (DM2), especially in
      industrialized countries where DM2 is the most frequent cause of chronic kidney
      disease. Diabetic nephropathy progression to ESRD (End Stage Renal Disease) may
      be slowed down only with a tight glycemic control, since no hypoglycemic drugs
      have been shown to possess renoprotective effects. Treatment with oral
      hypoglycemic agents should be closely and regularly monitored in patients with
      diabetic nephropathy since the decline of renal function below 60 ml/min of
      glomerular filtration rate (GFR) could cause multiple pharmacokinetic
      alterations. It may expose the patient to serious side effects if cautious dose
      reduction or even withdrawal of these drugs is not considered. Pharmacological
      approaches to the treatment of diabetes type 2 include the traditional oral
      hypoglycemic drugs (insulin sensitizers, insulin secretagogues and drugs
      inhibiting the absorption of glucose), incretin system drugs (orally or
      intravenously administered) and insulin therapy, if these drugs are insufficient
      or are contraindicated. The objective of this review is to evaluate the evidence
      regarding the use of oral hypoglycemic agents (with particular attention to the
      DPP-4 inhibitors) in diabetes type 2 with chronic kidney disease stage III- IV
      and ESRD, while in case of eGFR > 60 ml / min no dosage adjustment is usually
      required. 

PMID- 24671842
TI  - [Goodpasture's disease: a case series].
AB  - Goodpasture's disease (GD) is an uncommon and severe autoimmune disorder caused
      by circulating autoantibodies directed against the glomerular basement membrane
      cross-reacting with the alveolar basement membrane. GD is clinically
      characterized by rapidly progressive glomerulonephritis, often associated with
      pulmonary hemorrhage representing a nephrological emergency. We present the
      clinical features of 9 cases, diagnosed in 1997-2012, in our Renal Unit. Contrary
      to previous reports, we found a predominance of GD in females and we observed
      unusual clinical patterns, such as the association with renal vein thrombosis in
      a pregnant patient, thrombosis of the pulmonary arteries and a late isolated
      recurrence of alveolitis. In dialysis-dependent patients, renal transplantation
      can represent an available treatment option. 

PMID- 24671843
TI  - [Hemodiafiltration with endogenous reinfusion in chronic inflammation: a possible
      therapeutic alternative?].
AB  - The patients under maintenance haemodialysis (HD) continue to have an
      unacceptably excess of mortality compared to general population, that may be
      explained by high prevalence of inflammation that significantly influences the
      survival of these patients. Indeed, chronic inflammation is very common in HD and
      it may cause malnutrition and progression of atherosclerotic disease by several
      pathogenetic mechanisms triggered by pro-inflammatory cytokines. Currently no
      pharmacological intervention is specifically targeted the idiopathic chronic
      inflammation. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis
      technique, highly biocompatible, that combines three depurative mechanisms:
      diffusion, convection and absorption. The ultrafiltrate is obtained from
      convective section of dialyzer (convection). It is regenerated by passing through
      the adsorbent macro-porous synthetic resin cartridge (absorption) and then it is
      reinfused into the second section of the filter (diffusion). This resin cartridge
      is able to absorb cytokines and other uremic toxins, whereas allows to pass
      nutrients and antioxidants, as amino acids and vitamins, with a consequent
      decrement of inflammation and oxidative stress. These characteristics suggest the
      use of HFR in HD patients affected by overt and idiopathic chronic inflammation.
      In these patients, we observed that the switching from Bic-HD to HFR allowed an
      improvement of inflammatory as testified by a significant decrement of serum
      levels of CRP IL-6, IL-1 and TNF- and a significant increase of albumin and pre
      albumin. Whether these favorable effects may modify the outcomes of these high
      risk patients, needs to be confirmed by studies ad-hoc. 

PMID- 24671845
TI  - [Healing with love. Ideas for an ethic of communication in the relationship
      between doctor and patient].
AB  - In the last few years we have witnessed an intense debate, in which different
      opinions coming from very different cultures agreed that our Western civilization
      is currently facing a crisis that primarily affects the human being, even before
      economy or culture. Everywhere we see a rising demand for ethical values and
      responsibility, able to embrace the whole human being. Medicine is obviously in
      the forefront in facing the challenges of our time because of its intrinsically
      moral dimension. The purpose of this essay is to entrust some thoughts about
      health care ethics and communication to the cinematic storytelling (The
      Motorcycle Diaries movie screenplay) and to the narrative (the plot of The Story
      of Grail, written by the medieval poet Chrtien de Troyes). The goal is to
      contribute to a new definition of terms in which the deepest dimension of the
      human being is considered, thus overcoming the gap between "scientific culture"
      and "humanities" 

PMID- 24671844
TI  - [The management of arteriovenous fistula for dialysis patients].
AB  - A well-functioning vascular access is a basic requirement for a good dialysis
      treatment. Among the vascular accesses, the Artero-venous fistula (FAV) with
      native vessels is preferred for increasing survival rate, reducing risk of
      infection and with fewer complications. This review examines some aspects
      concerning the preparation and the surveillance of AVF. 

PMID- 24671846
TI  - [The bilateral renal lymphoma: an incurable disease? Case report].
AB  - The bilateral primary renal lymphoma (PRL) is a rare disease with a high
      mortality rate (75% within the first year). We report the case of a fifty-three
      years old women observed in January 2011 for renal colic. Ultrasonography showed
      hypoechoic lobular formations in the kidney. Blood tests showed: creatinine 1.8
      mg/dl, urea 75 mg/dl , Creatinine Clerance 35 ml/m, hemoglobinemia 11 g/dl, with
      blood cells 8.500/mcL, Albumin 2.8 g/dl, Beta -2 micro - 27.3/mL. Proteinuria was
      0.3 g/24 hours. The CT scan showed kidneys with larger dimensions and multiple
      hypodense areas infiltrating the renal parenchyma with contrast-enhanced low in
      which kidneys had lesions similar to "leopard skin". The CT scan showed no
      enlarged lymph nodes. Renal biopsy showed: renal parenchyma largely occupied by
      infiltration of lymphoid elements, small and medium-sized, densely packed with
      compression of the tubular structures . Immunofluorescence for immunoglobulin
      (Ig) G, IgA, IgM, C3, C4, C1q, fibrinogen, kappa and lambda were negative. The
      bone marrow biopsy excluded lymphomatous infiltration. The histological diagnosis
      was "non-Hodgkin's B-cell lymphoma"; the clinical diagnosis was LRBP. The patient
      was treated by 6 cycles of R-CHOP-21 protocol (rituximab - endoxan, adriblastina
      , vincristine, prendnisone), the latter of which practiced in August 2011. The pt
      is currently in follow-up hematology and nephrology . The first TAC control , in
      October 2011, showed a complete regression of the lesions infiltrating . This
      finding was confirmed by two other CT scan performed in February and October
      2012. The last blood tests of February 2013 showed : creatinine 1.1 mg / dl ,
      Urea 40 mg/dl, proteinuria absent. Currently, the pt is asymptomatic and is being
      treated by low dose of ACE inhibitor. The bilateral PRL is considered a severe
      disease with one-year mortality of 75% . The successful outcome of the case
      described can be attributed to haematological therapy and to the early diagnosis.

PMID- 24671847
TI  - [Inhibition of the renin-angiotensin system in HIV nephropathy].
AB  - It is estimated that 1-2 % of patients starting dialysis suffers from kidney
      disease associated with HIV infection. HIV-associated nephropathy ( HIVAN )
      develops in about 10% of people living with HIV , with different preference for
      Blacks and Hispanics . Since the beginning of large-scale use of antiretroviral
      therapy (ART), the HIVAN has been characterized by a rapid decline in renal
      function , with progression to ESRD ( End - Stage Renal Disease ). Aside from HIV
      direct damage to the nephron, numerous experimental observations support the
      argument that the agiotensina II contributes to the podocytes damage. Treatment
      with ACE - inhibitors (ACE - Is) , as well as the one with angiotensin receptor
      blockers ( ARBs), may attenuate the decline in renal function in HIVAN . However,
      clinical data on the effects of these antihypertensive agents in HIV-infected
      individuals are still scarce and doubts have yet to be adequately addressed. In
      the following, we analyze the studies that have investigated the use of ACE -Is
      and ARBs in the treatment of hypertension and albuminuria in patients with HIVAN.

PMID- 24671848
TI  - [Communication and health].
AB  - The Italian State protects health because it represents one of the basic
      necessities of man and the essential condition for the existence and proper
      functioning of the social and civic life of the citizen. The health system has
      recently undergone a substantial spending cuts: regardless of human capital,
      technological and financial provision, however all hospitals must be able to meet
      the demands/expectations of care of the patient as a whole, made of organic
      needs, psychological and relational. We need to "humanize" the medical treatment.
      All health care workers should be prepared to "welcome/cure" the patient in the
      most atraumatic as possible, placing it at the center of a system that revolves
      around Him. Communicate effectively with a person who is going through a
      particular moment of his life is not so simple and immediate. In these cases, the
      preparation and the sensitivity of the practitioner to make a difference: it is
      necessary that sender and receiver are tuned to the "same wavelength. In other
      words, the speaker should make themselves understood adapting their speech to the
      hypothetical interlocutor's cognitive abilities. Proper communication is
      therefore an essential element of the process of patient care, today more and
      more able and entitled to make any judgments especially on how, type and timing
      of relationships with healthcare professionals. 

PMID- 24671849
TI  - Evaluating community engagement as part of the public health system.
AB  - Community participation and leadership is a central tenet of public health policy
      and practice. Community engagement approaches are used in a variety of ways to
      facilitate participation, ranging from the more utilitarian, involving lay
      delivery of established health programmes, to more empowerment-oriented
      approaches. Evaluation methods within public health, adapted from clinical
      medicine, are most suited to evaluating community engagement as an
      'intervention', in the utilitarian sense, focusing on the health impacts of
      professionally determined programmes. However, as communities are empowered and
      professional control is relinquished, it is likely to be harder to capture the
      full effects of an intervention and so the current evidence base is skewed away
      from knowledge about the utility of these approaches. The aim of this paper is to
      stimulate debate on the evaluation of community engagement. Building on current
      understandings of evaluation within complex systems, the paper argues that what
      is needed is a paradigm shift from viewing the involvement of communities as an
      errant form of public health action, to seeing communities as an essential part
      of the public health system. This means moving from evaluation being exclusively
      focused on the linear causal chain between the intervention and the target
      population, to seeking to build understanding of whether and how the lay
      contribution has impacted on the social determinants of health, including the
      system through which the intervention is delivered. The paper proposes some
      alternative principles for the evaluation of community engagement that reflect a
      broader conceptualisation of the lay contribution to public health. 

PMID- 24671853
TI  - Three-dimensional modeling of the P. falciparum genome during the erythrocytic
      cycle reveals a strong connection between genome architecture and gene
      expression.
AB  - The development of the human malaria parasite Plasmodium falciparum is controlled
      by coordinated changes in gene expression throughout its complex life cycle, but
      the corresponding regulatory mechanisms are incompletely understood. To study the
      relationship between genome architecture and gene regulation in Plasmodium, we
      assayed the genome architecture of P. falciparum at three time points during its
      erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with
      next-generation sequencing technology (Hi-C), we obtained high-resolution
      chromosomal contact maps, which we then used to construct a consensus three
      dimensional genome structure for each time point. We observed strong clustering
      of centromeres, telomeres, ribosomal DNA, and virulence genes, resulting in a
      complex architecture that cannot be explained by a simple volume exclusion model.
      Internal virulence gene clusters exhibit domain-like structures in contact maps,
      suggesting that they play an important role in the genome architecture. Midway
      during the erythrocytic cycle, at the highly transcriptionally active trophozoite
      stage, the genome adopts a more open chromatin structure with increased
      chromosomal intermingling. In addition, we observed reduced expression of genes
      located in spatial proximity to the repressive subtelomeric center, and
      colocalization of distinct groups of parasite-specific genes with coordinated
      expression profiles. Overall, our results are indicative of a strong association
      between the P. falciparum spatial genome organization and gene expression.
      Understanding the molecular processes involved in genome conformation dynamics
      could contribute to the discovery of novel antimalarial strategies. 

PMID- 24671852
TI  - Inputs drive cell phenotype variability.
AB  - What is the significance of the extensive variability observed in individual
      members of a single-cell phenotype? This question is particularly relevant to the
      highly differentiated organization of the brain. In this study, for the first
      time, we analyze the in vivo variability within a neuronal phenotype in terms of
      input type. We developed a large-scale gene-expression data set from several
      hundred single brainstem neurons selected on the basis of their specific synaptic
      input types. The results show a surprising organizational structure in which
      neuronal variability aligned with input type along a continuum of sub-phenotypes
      and corresponding gene regulatory modules. Correlations between these regulatory
      modules and specific cellular states were stratified by synaptic input type.
      Moreover, we found that the phenotype gradient and correlated regulatory modules
      were maintained across subjects. As these specific cellular states are a function
      of the inputs received, the stability of these states represents "attractor"-like
      states along a dynamic landscape that is influenced and shaped by inputs,
      enabling distinct state-dependent functional responses. We interpret the
      phenotype gradient as arising from analog tuning of underlying regulatory
      networks driven by distinct inputs to individual cells. Our results change the
      way we understand how a phenotypic population supports robust biological function
      by integrating the environmental experience of individual cells. Our results
      provide an explanation of the functional significance of the pervasive
      variability observed within a cell type and are broadly applicable to
      understanding the relationship between cellular input history and cell phenotype
      within all tissues. 

PMID- 24671854
TI  - Influence of CYP1A1, GST polymorphisms and susceptibility risk of chronic myeloid
      leukemia in Syrian population.
AB  - In the present study, we investigated the associations of polymorphisms in
      cytochrome P450 gene (CYP1A1), glutathione S-transferase genes (GSTM1 and GSTT1)
      with chronic myelogenous leukemia (CML). A total of 126 patients with CML and 172
      healthy volunteers were genotyped, and the DNA was isolated from their blood
      samples. The polymorphisms were assessed by polymerase chain reaction (PCR)
      restriction fragment length polymorphism-based methods and multiplex PCR.
      Logistic regression analyses showed significant risk of CML associated with
      CYP1A1 Val allele [odds ratio (OR) 3.3, 95% confidence intervals (CI) 1.96-5.53],
      (p < 0.0001) while CYP1A1 Val/Val homozygotes were observed only in the CML
      patients. There was statistically significant difference in the frequency of
      GSTM1 and GSTT1 null genotypes. The GSTT1-null genotype was slightly higher in
      27% of CML cases and 16.7% of controls (OR 1.98, 95% CI 1.12-3.5) (p < 0.020).
      The GSTM1 null was higher in 42.8% of CML cases and 22.7% of controls (OR 2.55,
      95% CI 1.54-4.22) (p < 0.00024). The individuals carrying CYP1A1 Ile/Val (AG) and
      GSTM1 null genotype have 9.9 times higher risk to be CML than those carrying
      CYP1A1 Ile/Ile (AA) and GSTM1 present genotype (OR 9.9, 95% CI 2.7-36.3) (p <
      0.0001). This suggests that the association of the GSTM1 null genotype, either
      alone or in combination with GSTT1 null, with CYP1AI heterozygous leads to the
      CML risk.

PMID- 24671855
TI  - c-Myc-induced, long, noncoding H19 affects cell proliferation and predicts a poor
      prognosis in patients with gastric cancer.
AB  - Gastric cancer (GC) is one of the most frequent cancers worldwide. Recent studies
      have shown that long noncoding RNAs (lncRNAs) play critical roles in multiple
      biological processes, including oncogenesis. The present study aimed to evaluate
      the potential role of lncRNA H19 in GC. qRT-PCR was performed to investigate the
      expression of H19 in tumor tissues and corresponding non-tumor lung tissues from
      80 patients with GC and in GC cell lines. The Kaplan-Meier method and Cox
      proportional hazards analysis were used to evaluate the association between H19
      expression and overall survival time (OS). The biological significance of H19 was
      evaluated using siRNAs in vitro. We also constructed a c-Myc plasmid to
      investigate the cause of the altered expression of H19 in the progression of GC.
      The results show that lncRNA H19 is overexpressed in tumor tissues compared with
      adjacent normal tissues. An advanced tumor-node-metastasis stage was positively
      correlated with increased H19 expression (P < 0.001), and a high H19 expression
      was associated with poor OS and can be regarded as an independent predictor of
      the OS of GC patients (P = 0.042). MTT and colony formation assays confirmed that
      H19 expression affects GC cell proliferation in vitro. Furthermore, exogenous c
      Myc significantly induces H19 expression, and the expression of H19 was
      positively correlated with the c-Myc levels in the 80 samples used in our study
      (Pearson correlation coefficient = -0.687). In conclusion, our study demonstrates
      that the altered expression of lncRNA H19, which is induced by c-Myc, is involved
      in the development and progression of GC by regulating cell proliferation and
      shows that H19 may be a potential diagnostic and prognostic target in patients
      with GC.

PMID- 24671856
TI  - Two cases of focal scrotal vitiligo successfully treated by autologous cultured
      melanocyte transplantation.
AB  - Vitiligo is an acquired cutaneous depigmentation disorder which has a deleterious
      effect on the psychosexual function of many individuals; the genitalia are the
      common site for depigmentation. Here, the authors report two cases of focal
      vitiligo affecting the scrotum of the genital organs which were successfully
      treated by autologous cultured melanocyte transplantation. Autologous cultured
      melanocyte transplantation on the scrotum is shown to be a relative effective
      method of treatment for vitiligo. 

PMID- 24671857
TI  - En bloc resection: does it really matter?

PMID- 24671858
TI  - Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for
      sedation during ERCP: prospective, randomized, double-blinded trial.
AB  - BACKGROUND AND STUDY AIM: The combination of midazolam and opioid has been widely
      used as a standard sedative regimen for endoscopic retrograde
      cholangiopancreatography (ERCP). Following recent evidence that dexmedetomidine
      may exert a synergistic effect in combination with midazolam, this study compared
      the sedative effect and adverse events of midazolam - meperidine -
      dexmedetomidine (MMD) and midazolam - meperidine during ERCP. PATIENTS AND
      METHODS: A total of 110 patients who were scheduled for ERCP were prospectively
      enrolled and randomly assigned, in a double-blind manner, to the MMD (n = 53) or
      midazolam - meperidine (n = 57) groups. Each patient received an intravenous (IV)
      bolus dose of midazolam and meperidine (0.06 mg/kg and 50 mg, 30 % reduction and
      25 mg for patients aged >= 65 years, respectively). To this dose, a continuous IV
      infusion of dexmedetomidine (1 MUg/kg/h; MMD group) or the same volume of normal
      saline (midazolam - meperidine group) was added. The sedation level (Ramsay
      Sedation Scale [RSS]) as well as hemodynamic and respiratory changes were
      assessed. RESULTS: Adequate sedation (RSS >= 3) was maintained during ERCP in
      75.5 % and 36.8 % of the MMD and midazolam - meperidine group, respectively (P <
      0.001). RSS scores were significantly higher in the MMD group (P < 0.001).
      Intraoperative bispectral index scores were significantly lower in the MMD group
      (P < 0.001) than in the midazolam - meperidine group. Lower additional (P =
      0.001) and total (P = 0.003) doses of midazolam were required in the MMD group.
      Patients in the MMD group showed lower pain scores (P < 0.001) and higher
      satisfaction scores (P < 0.001). Desaturation occurred more frequently in the
      midazolam - meperidine group (11 vs. 1; P = 0.003). CONCLUSIONS: The addition of
      dexmedetomidine to the midazolam - meperidine regimen provided better sedative
      efficacy and a superior safety profile during ERCP compared with a midazolam -
      meperidine regimen.This trial was registered at ClinicalTrials.gov Identifier
      (NCT01404689).

PMID- 24671860
TI  - Endoscopic ultrasound-guided fine-needle aspiration for the differential
      diagnosis of intraductal papillary mucinous neoplasms and size stratification for
      surveillance.

PMID- 24671861
TI  - Reply to Kadayifci and Brugge.

PMID- 24671865
TI  - The study of drugs for rare disorders: harnessing research contributions by
      Canadian academic institutions.
AB  - The development of an orphan drug policy with the focus on essential research
      that may be undertaken in Canada's universities. 

PMID- 24671864
TI  - Endoscopic submucosal dissection.

PMID- 24671866
TI  - Information, consent and treatment of patients with Morgellons disease: an
      ethical perspective.
AB  - Morgellons is a medically contested diagnosis with foremost dermatological
      symptoms. Patients experience fibers emerging from the skin, together with a
      range of other somatic, psychiatric, and neurological complaints. Within the
      medical community, it is generally held to be a variation of delusional
      parasitosis/delusional infestation, which is usually treated with antipsychotics.
      Little attention has been paid in the literature to the ethical aspects of
      treating patients with Morgellons disease. The communicative strategies suggested
      in the literature display significant ethical issues, primarily the use of
      therapeutic privilege, i.e. withholding information from the patient. Since this
      limits patient autonomy, that approach is ethically problematic. Instead, the
      physician has an ethical obligation to respect the patient's autonomy, provide
      full information, and seek consent before initiating a psychiatric referral. 

PMID- 24671867
TI  - Dipeptidyl peptidase-4 inhibitors have protective effect on cognitive impairment
      in aged diabetic patients with mild cognitive impairment.
AB  - BACKGROUND: Older adults with type 2 diabetes have an increased risk for mild and
      severe cognitive impairment probably as consequence of chronic hyperglycemia or
      fasting plasma glucose levels. Variability in glucose level and recurrent
      hypoglycemic episodes are also associated with cognitive impairment. Dipeptidyl
      peptidase-4 inhibitor (DPP-4I) therapy affects glycemic variability. The purpose
      of this study was to evaluate the effect of DPP-4I therapy on changes in
      cognitive function in older patients with type 2 diabetes complicated by mild
      cognitive impairment. METHODS: This retrospective longitudinal study used data
      from a database of 240 older patients with type 2 diabetes, "drug naive,"
      affected by mild cognitive impairment, subsequently treated for 2 years with
      antidiabetic drugs (DPP-4I group: DPP-4I + metformin, n = 120; SU group:
      sulfonylurea + metformin, n = 120) and reassessed in our ambulatory by
      comprehensive clinical, cognitive, instrumental examinations, and continuous
      subcutaneous glucose monitoring. RESULTS: At baseline, larger mean amplitude of
      glycemic excursion values correlated with poorer Mini-Mental State Examination
      and composite cognitive function scores. We found that higher body mass index,
      higher 2-hour postprandial glucose, and greater mean amplitude of glycemic
      excursion values measured at baseline were significant independent predictors of
      cognitive worsening. In addition, reduction in mean amplitude of glycemic
      excursions and the use of DPP-4I therapy predicted improvement in cognitive
      functions. CONCLUSIONS: In older patients with type 2 diabetes affected by mild
      cognitive impairment, DPP-4I administration improves glucose control and protects
      against worsening in cognitive functioning.

PMID- 24671868
TI  - Redefining cancer: a new paradigm for better and faster treatment innovation.
AB  - Common cancers may arise from several different mutations, and each causative
      mutation may require different treatment approaches. There are also several
      mechanisms by which malignancies may become resistant to therapy, and each
      mechanism will also require a different therapeutic strategy. Hence, the paradigm
      of devising therapies based on tumor type is suboptimal. Each common malignancy
      may now be regarded as a collection of morphologically similar but molecularly
      distinct orphan diseases, each requiring unique approaches. Current strategies
      that employ randomized clinical trials (RCTs) in unselected patients carry a high
      risk of misleading results. Available data suggest that it is reasonable to grant
      marketing approval for new anticancer agents based solely on high single-agent
      response rates in small phase I-II studies involving molecularly-defined patient
      groups where benefit from other therapies is unlikely. This could markedly speed
      patient access to important therapies while reducing health care costs by
      slashing drug development costs. Feasible post-approval surveillance procedures
      could provide ongoing monitoring of drug safety. While assessment of drug
      combinations would be more complex due to variable contributions of each
      component, new strategies have been proposed. In addition to savings from more
      efficient clinical trials methods, it is essential that we also markedly reduce
      costs of complying with clinical research regulations. Compliance is too
      cumbersome and expensive, and current regulatory inflexibility markedly slows
      progress while escalating health care costs. This requires urgent attention.
      Regulatory approaches intended to enhance safety may instead potentially cost far
      more life-years than they save by delaying approval of effective therapies.  

PMID- 24671869
TI  - Local recurrence after endoscopic mucosal resection of nonpedunculated colorectal
      lesions: systematic review and meta-analysis.
AB  - BACKGROUND AND STUDY AIMS: Local recurrence has been observed after endoscopic
      mucosal resection (EMR) of nonpedunculated colorectal lesions. The indications
      for follow-up colonoscopy and the optimal time interval are currently unclear.
      The aims of this systematic review were to assess the frequency of local
      recurrence after EMR, to identify risk factors for recurrence, and to provide
      follow-up recommendations. METHODS: A literature search was performed in PubMed,
      EMBASE, and the Cochrane Library. EMR was defined as endoscopic snare resection
      after submucosal fluid injection for removal of nonpedunculated adenomas and
      early carcinomas. Local recurrence was subdivided into early recurrence (detected
      at the first follow-up colonoscopy) and late recurrence (detected after >= 1
      previous normal colonoscopy). A random effects meta-analysis was performed to
      calculate the pooled estimate of risk of recurrence. RESULTS: A total of 33
      studies were included. The mean recurrence risk after EMR was 15 % (95 %
      confidence interval [CI] 12 % - 19 %). Recurrence risk was higher after piecemeal
      resection (20 %; 95 %CI 16 % - 25 %) than after en bloc resection (3 %; 95 %CI 2
      % - 5 %; P < 0.0001). In 15 studies that differentiated between early and late
      recurrences, 152/173 recurrences (88 %) occurred early. In four studies with
      follow-up at 3, 6, and >= 12 months, 19/25 (76 %) recurrences were detected at 3
      months, increasing to 24 (96 %) at 6 months. In multivariable analysis, only
      piecemeal resection was associated with recurrence (3 of 3 studies). CONCLUSION:
      Local recurrence after EMR of nonpedunculated colorectal lesions occurs in 3 % of
      en bloc resections and 20 % of piecemeal resections. Piecemeal resection was the
      only independent risk factor for recurrence. As more than 90 % of recurrences are
      detected at 6 months after EMR, we propose that 6 months is the optimal initial
      follow-up interval.

PMID- 24671871
TI  - A survey of the preferences of primary care physicians regarding the comanagement
      with specialists of children with rare or complex conditions.
AB  - OBJECTIVES: To assess primary care pediatric providers' comfort with co-managing
      patients with rare conditions. METHODS: A survey was sent via an electronic link
      to pediatricians and family practitioners. Chi-square test of significance and
      Fisher's exact test were used for categorical variable comparisons and the
      Student's t test was used for continuous variable comparisons. RESULTS: Most of
      the providers believed that care decisions are most frequently made by the
      specialist with consultation with the primary care clinician. The most common
      source of information is direct communication from the specialist. The most
      effective tool to increase clarity and comfort about provider roles was an active
      care plan identifying current care needs, who will act on the plan, and when the
      action should be completed. CONCLUSIONS: Coordinated co-management in which
      caregiving roles are explicitly defined and tools are available for the timely
      exchange of information among all key participants warrants further study.

PMID- 24671872
TI  - Prescription of home oxygen therapy to very low birth weight infants in Germany:
      a nationwide survey.
AB  - OBJECTIVE: There is no consensus on prescription of home oxygen therapy to
      infants in Germany. We hypothesized that this causes considerable variability in
      prescribing home oxygen to infants. STUDY DESIGN: A structured questionnaire
      involving management of home oxygen therapy was sent to all German pediatric
      departments (n = 293). RESULTS: Response rate was 84% (247/293). SpO2 cutoff
      values below which oxygen therapy was considered indicated showed a wide range
      (80% to 94%, mean 90%). Respondents admitting >50 very low birth weight infants
      annually significantly more frequently prescribed home oxygen (P < .001) and
      aimed for SpO2 levels closer to the physiological range than those admitting less
      very low birth weight infants (P = .046). CONCLUSION: Management of pediatric
      home oxygen therapy is diverse in Germany. Optimal SpO2 targets have to be
      further investigated by controlled studies and German guidelines should be
      established. Until then practice should abide by existing foreign guidelines.

PMID- 24671873
TI  - Evaluation of a social pediatrics elective: transforming students' perspective
      through reflection.
AB  - OBJECTIVE: The aim of this study was to examine aspects of a social pediatrics
      elective that led to student self-reflection and transformation. METHODS: To
      assess student learning from our social pediatric elective, we retrospectively
      evaluated self-reflection papers. We focused on the effectiveness of the
      educational approach to inspire students to incorporate the social determinants
      of health into their practice. Furthermore, in each reflection paper, we looked
      for evidence of different phases of transformation. RESULTS: The social
      determinants of health were the most commonly described theme. Poverty was
      mentioned directly or described implicitly in almost all papers. For many
      students, seeing the social context of patients in real life, whether in a
      special clinic or at a home visit, was a disturbing and disorienting experience
      that triggered transformation. CONCLUSION: The use of reflection papers in the
      evaluation of a social pediatric elective documented transformative learning.

PMID- 24671870
TI  - The potential of antiseizure drugs and agents that act on novel molecular targets
      as antiepileptogenic treatments.
AB  - A major goal of contemporary epilepsy research is the identification of therapies
      to prevent the development of recurrent seizures in individuals at risk,
      including those with brain injuries, infections, or neoplasms; status
      epilepticus; cortical dysplasias; or genetic epilepsy susceptibility. In this
      review we consider the evidence largely from preclinical models for the
      antiepileptogenic activity of a diverse range of potential therapies, including
      some marketed antiseizure drugs, as well as agents that act by immune and
      inflammatory mechanisms; reduction of oxidative stress; activation of the
      mammalian target of rapamycin or peroxisome proliferator-activated receptors
      gamma pathways; effects on factors related to thrombolysis, hematopoesis, and
      angiogenesis; inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reducatase;
      brain-derived neurotrophic factor signaling; and blockade of alpha2 adrenergic
      and cannabinoid receptors. Antiepileptogenesis refers to a therapy of which the
      beneficial action is to reduce seizure frequency or severity outlasting the
      treatment period. To date, clinical trials have failed to demonstrate that
      antiseizure drugs have such disease-modifying activity. However, studies in
      animal models with levetiracetam and ethosuximide are encouraging, and clinical
      trials with these agents are warranted. Other promising strategies are inhibition
      of interleukin 1beta signaling by drugs such as VX-765; modulation of sphingosine
      1-phosphate signaling by drugs such as fingolimod; activation of the mammalian
      target of rapamycin by drugs such as rapamycin; the hormone erythropoietin; and,
      paradoxically, drugs such as the alpha2 adrenergic receptor antagonist
      atipamezole and the CB1 cannabinoid antagonist SR141716A (rimonabant) with
      proexcitatory activity. These approaches could lead to a new paradigm in epilepsy
      drug therapy where treatment for a limited period prevents the occurrence of
      spontaneous seizures, thus avoiding lifelong commitment to symptomatic treatment.

PMID- 24671874
TI  - Screening obese children and adolescents for prediabetes and/or type 2 diabetes
      in pediatric practices: a validation study.
AB  - BACKGROUND: Increased prevalence of type 2 diabetes mellitus (T2DM) makes it
      important for pediatricians to use effective screening tools for risk assessment
      of prediabetes/T2DM in children. METHODS: Children (n = 149) who had an oral
      glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) were studied.
      American Diabetes Association recommended screening criteria-HbA1c >=5.7% and
      fasting plasma glucose (FPG) >=100 mg/dL-were compared against OGTT. The
      homeostatic model assessment of insulin resistance (HOMA-IR), a mathematical
      index derived from fasting insulin and glucose, was compared with OGTT. We
      studied whether combining screening tests (HbA1c and fasting glucose or HbA1c and
      HOMA-IR) improved accuracy of prediction of the OGTT. RESULTS: HbA1c of >=5.7%
      had a sensitivity of 75% and specificity of 57% when compared with the OGTT.
      Combining screening tests (HbA1c >=5.7% and FPG >=100 mg/dL; HbA1c >=5.7% and
      HOMA-IR >=3.4) resulted in improved sensitivity (95.5% for each), with the HbA1c
      FPG doing better than the HbA1c-HOMA-IR combination in terms of ability to rule
      out prediabetes (likelihood ratio [LR]) negative. 0.07 vs 0.14). CONCLUSIONS:
      HbA1c of >=5.7% provided fair discrimination of glucose tolerance compared with
      the OGTT. The combination of HbA1c and FPG is a useful method for identifying
      children who require an OGTT.

PMID- 24671875
TI  - How well are we preparing pediatricians to manage seizures and epilepsy? A single
      center questionnaire-based pilot study.
AB  - OBJECTIVE: To assess the knowledge of pediatric residents regarding principles of
      management of seizures and epilepsy. METHODS: A 10-item multiple-choice
      questionnaire with single correct response each (scored as 1) was administered to
      pediatric residents at an academic hospital. RESULTS: Out of 92 questionnaires,
      73 were returned (79.3%). The mean score was 5 +/- 1.9 (range = 1 to 9). Most
      correct responses (53/70, 75.5%) were received for the question on diagnosis of
      epilepsy. Questions on febrile seizures and on pharmacology of valproic acid
      received <50% correct responses among senior as well as junior residents, with no
      significant improvement in the correct response rate of senior residents.
      CONCLUSIONS: Deficiencies exist in pediatric residents' knowledge of seizures and
      epilepsy, especially with respect to febrile seizures and pharmacology of
      antiepileptic medications. Improved mechanisms to promote understanding in these
      areas are needed during pediatric training.

PMID- 24671877
TI  - Toll-like receptor 4 regulates lipopolysaccharide-induced inflammation and
      lactation insufficiency in a mouse model of mastitis.
AB  - Lactation mastitis is a debilitating inflammatory breast disease in postpartum
      women. Disease severity is associated with markers of inflammation rather than
      bacterial load, suggesting that immune-signaling pathways activated in the host
      are important in the disease pathology. The role of the innate pattern
      recognition receptor toll-like receptor 4 (TLR4) in progression and resolution of
      mastitislike disease was investigated in a mouse model. Lipopolysaccharide in
      Matrigel (10 MUg/10 MUl) was administered into the teat canal of lactating Tlr4
      null mutant and wild-type mice to induce a localized area of inflammation.
      Mastitis induction resulted in a marked influx of RB6-positive neutrophils and
      F4/80-positive macrophages, which was higher in Tlr4(-/-) mice compared to wild
      type mice. Tlr4 null mutation resulted in an altered immune-signaling fingerprint
      following induction of mastitis, with attenuated serum cytokines, including
      CXCL1, CCL2, interleukin 1 beta, and tumor necrosis factor alpha compared to wild
      type mice. In both genotypes, the localized area of inflammation had resolved
      after 7 days, and milk protein was evident. However, the mammary glands of wild
      type mice exhibited reduced capacity for milk production, with decreased percent
      area populated with glandular epithelium and decreased abundance of nuclear
      phosphorylated signal transducer and activator of transcription 5 compared to
      Tlr4 null mice. This study demonstrates that inflammatory pathways activated in
      the host are critically important in mastitis disease progression and suggests
      that lactation insufficiency associated with mastitis may be a consequence of
      TLR4-mediated inflammation, rather than the bacterial infection itself. 

PMID- 24671876
TI  - Generation of transgenic pigs by cytoplasmic injection of piggyBac transposase
      based pmGENIE-3 plasmids.
AB  - The process of transgenesis involves the introduction of a foreign gene, the
      transgene, into the genome of an animal. Gene transfer by pronuclear
      microinjection (PNI) is the predominant method used to produce transgenic
      animals. However, this technique does not always result in germline transgenic
      offspring and has a low success rate for livestock. Alternate approaches, such as
      somatic cell nuclear transfer using transgenic fibroblasts, do not show an
      increase in efficiency compared to PNI, while viral-based transgenesis is
      hampered by issues regarding transgene size and biosafety considerations. We have
      recently described highly successful transgenesis experiments with mice using a
      piggyBac transposase-based vector, pmhyGENIE-3. This construct, a single and self
      inactivating plasmid, contains all the transpositional elements necessary for
      successful gene transfer. In this series of experiments, our laboratories have
      implemented cytoplasmic injection (CTI) of pmGENIE-3 for transgene delivery into
      in vivo-fertilized pig zygotes. More than 8.00% of the injected embryos developed
      into transgenic animals containing monogenic and often single transgenes in their
      genome. However, the CTI technique was unsuccessful during the injection of in
      vitro-fertilized pig zygotes. In summary, here we have described a method that is
      not only easy to implement, but also demonstrated the highest efficiency rate for
      nonviral livestock transgenesis. 

PMID- 24671878
TI  - Estimated diversity of messenger RNAs in each murine spermatozoa and their
      potential function during early zygotic development.
AB  - To study the diversity of mRNAs in murine spermatozoa and their potential
      function during zygotic development, total RNAs in murine spermatozoa were
      sequenced via RNA-Seq and analyzed through bioinformatics techniques. The
      delivery and translation of sperm-borne mRNA in fertilized oocyte were detected
      using RT-PCR (reverse transcription-polymerase chain reaction), Western blot, and
      immunofluorescence. A total of 35 288 825 reads matching 33 039 transcripts,
      including 27 310 coding transcripts, were obtained. Based on our analyses, we
      hypothesized that the transcripts with RPKM (reads per kilobase of exon model per
      million mapped reads) higher than six may exist in each sperm cell as
      consistently retained transcripts. There were 4885 consistent transcripts in each
      sperm, and the remainder were randomly retained. If the baseline RPKM increased,
      the remaining coding transcripts were more likely related to reproduction and
      development. The sperm-borne transcripts Wnt4 and Foxg1 were delivered into
      fertilized oocytes on fertilization. Furthermore, Wnt4 was translated into
      protein in zygotes, whereas Foxg1 was not translated. In conclusion,
      approximately 4885 mRNAs were present in each murine spermatozoon, and the
      spermatozoal mRNAs related to reproduction and development were more likely
      retained. The sperm-borne mRNA Wnt4 was delivered into the fertilized oocyte and
      translated, evidence of a paternal effect on zygotic development. 

PMID- 24671879
TI  - Developmental expression of Musashi-1 and Musashi-2 RNA-binding proteins during
      spermatogenesis: analysis of the deleterious effects of dysregulated expression.
AB  - Spermatogenesis is a complex developmental process whereby diploid spermatogenic
      stem cells become haploid and undergo a series of morphological changes to
      produce physically mature spermatozoa. Crucial to this process are a number of
      RNA-binding proteins, responsible for the posttranscriptional control of
      essential mRNAs and particularly pertinent to the two periods of inactive
      transcription that occur in spermatogenesis. One such group of RNA-binding
      proteins is the Musashi family, specifically Musashi-1 (MSI1) and Musashi-2
      (MSI2), which act as key translational regulators in various stem cell
      populations and have been linked with the induction of tumorigenesis. In the
      present study, we examined the differential expression of mammalian MSI1 and MSI2
      during germ cell development in the mouse testis. MSI1 was found to be
      predominately localized in mitotic gonocytes and spermatogonia, whereas MSI2 was
      detected in meiotic spermatocytes and differentiating spermatids. Extensive
      examination of the function of Musashi in spermatogenesis was achieved through
      the use of two transgenic mouse models with germ cell-specific overexpression of
      full-length isoforms of Msi1 or Msi2. These models demonstrated that aberrant
      expression of either Msi1 or Msi2 has deleterious effects on normal
      spermatogenesis, with Msi2 overexpression resulting in male sterility. Studies
      undertaken on human testicular seminoma tumors provide further insights into the
      relevance of MSI1 and MSI2 overexpression as diagnostic markers to human stem
      cell cancers. Overall this study provides further evidence for the unique
      functions that RNA-binding protein isoforms occupy within spermatogenesis, and
      introduces the potential manipulation of the Musashi family proteins to elucidate
      the mechanisms of posttranscriptional gene expression during germ cell
      development. 

PMID- 24671880
TI  - Coevolution of positively selected IZUMO1 and CD9 in rodents: evidence of
      interaction between gamete fusion proteins?
AB  - Proteins involved in sexual reproduction are known to evolve rapidly, often as
      the result of positive Darwinian selection, although the selective forces driving
      such adaptive changes are poorly understood. A process of coevolution between
      proteins in male and female gametes may promote rapid divergence of fertilization
      proteins. In the mouse, only two proteins have been shown so far to be essential
      for sperm-egg fusion, IZUMO1 in the sperm cell and CD9 in the egg. The role of
      these proteins has not been fully elucidated, and it has been suggested that they
      may act as fusogens, interacting in trans with proteins on the other cell, or
      regulators of fusogens through cis interactions. Here we analyze the evolution of
      IZUMO1 and CD9 in a group of rodent species. To assess possible protein
      interactions between IZUMO1 and CD9, we examined potential coevolution based on
      analyses of correlated evolutionary rates. We found evidence that both proteins
      evolve adaptively, with a more intense signal of positive selection in IZUMO1. In
      addition, our findings suggest that these proteins may have some form of
      interaction, although they have not been regarded as fusogens interacting
      directly with each other. The adaptive divergence of IZUMO1 and CD9 could
      influence reproductive compatibility, and, thus, these proteins may participate
      in the establishment of specific sperm-egg recognition systems. Further studies
      are required to uncover the role of IZUMO1 and CD9 during gamete fusion in order
      to understand the molecular basis of their coevolution, as other selective forces
      could also lead to general signatures of coevolution. 

PMID- 24671881
TI  - Unresolved questions concerning mammalian sperm acrosomal exocytosis.
AB  - In recent years, the study of mammalian acrosomal exocytosis has produced some
      major advances that challenge the long-held, general paradigms in the field.
      Principally, the idea that sperm must be acrosome-intact to bind to the zona
      pellucida of unfertilized eggs, based largely on in vitro fertilization studies
      of mouse oocytes denuded of the cumulus oophorus, has been overturned by
      experiments using state-of-the-art imaging of cumulus-intact oocytes and
      fertilization experiments where eggs were reinseminated by acrosome-reacted sperm
      recovered from the perivitelline space of zygotes. In light of these results,
      this minireview highlights a number of unresolved questions and emphasizes the
      fact that there is still much work to be done in this exciting field. Future
      experiments using recently advanced technologies should lead to a more complete
      and accurate understanding of the molecular mechanisms governing the
      fertilization process in mammals. 

PMID- 24671883
TI  - Aberrant expressions of delta-protocadherins in the brain of Npc1 mutant mice.
AB  - Niemann-Pick type C1 (NPC1) disease is an autosomal recessive disorder
      characterized by dysmyelination and neurodegeneration, which can result in the
      death of patients in early childhood in some cases. Members of the delta
      protocadherins (Pcdhs) play important roles in neurogenesis and brain
      development. In this study, we compared expression profiles of Pcdhs in the brain
      of both wild-type and Npc1 mutant mice from postnatal day (P) 9 onwards by in
      situ hybridization. Our data show that laminar distribution of some Pcdhs in the
      cerebral cortex of Npc1 mutated mice is different from that of wild-type mice.
      Furthermore, expressions of Pcdhs by oligodendrocytes in the corpus callosum and
      by Purkinje cells and granular cells in the cerebellum are strongly decreased in
      Npc1 mutated mice at later stages. Taken together, our data suggest that aberrant
      expression of Pcdhs is a pathological process accompanied by neurodegeneration in
      Npc1 mutant mice.

PMID- 24671882
TI  - CHEMERIN (RARRES2) decreases in vitro granulosa cell steroidogenesis and blocks
      oocyte meiotic progression in bovine species.
AB  - CHEMERIN, or RARRES2, is a new adipokine that is involved in the regulation of
      adipogenesis, energy metabolism, and inflammation. Recent data suggest that it
      also plays a role in reproductive function in rats and humans. Here we studied
      the expression of CHEMERIN and its three receptors (CMKLR1, GPR1, and CCRL2) in
      the bovine ovary and investigated the in vitro effects of this hormone on
      granulosa cell steroidogenesis and oocyte maturation. By RT-PCR, immunoblotting,
      and immunohistochemistry, we found CHEMERIN, CMKLR1, GPR1, and CCRL2 in various
      ovarian cells, including granulosa and theca cells, corpus luteum, and oocytes.
      In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers
      metformin and rosiglitazone-increased rarres2 mRNA expression whereas they
      decreased cmklr1, gpr1, and cclr2 mRNA expression. Furthermore, TNF alpha and
      ADIPONECTIN significantly increased rarres2 and cmklr1 expression, respectively.
      In cultured bovine granulosa cells, human recombinant CHEMERIN (hRec, 200 ng/ml)
      reduced production of both progesterone and estradiol, cholesterol content, STAR
      abundance, CYP19A1 and HMGCR proteins, and the phosphorylation levels of
      MAPK3/MAPK1 in the presence or absence of FSH (10(-8) M) and IGF1 (10(-8) M). All
      of these effects were abolished by using an anti-CMKLR1 antibody. In bovine
      cumulus-oocyte complexes, the addition of hRec (200 ng/ml) in the maturation
      medium arrested most oocytes at the germinal vesicle stage, and this was
      associated with a decrease in MAPK3/1 phosphorylation in both oocytes and cumulus
      cells. Thus, in cultured bovine granulosa cells, hRec decreases steroidogenesis,
      cholesterol synthesis, and MAPK3/1 phosphorylation, probably through CMKLR1.
      Moreover, in cumulus-oocyte complexes, it blocked meiotic progression at the
      germinal vesicle stage and inhibited MAPK3/1 phosphorylation in both the oocytes
      and cumulus cells during in vitro maturation. 

PMID- 24671884
TI  - A re-evaluation and validation of ontogeny functions for cytochrome P450 1A2 and
      3A4 based on in vivo data.
AB  - BACKGROUND AND OBJECTIVES: Current cytochrome P450 (CYP) 1A2 and 3A4 ontogeny
      profiles, which are derived mainly from in vitro studies and incorporated in
      paediatric physiologically based pharmacokinetic models, have been reported to
      under-predict the in vivo clearances of some model substrates in neonates and
      infants. METHOD: We report ontogeny functions for these enzymes as paediatric to
      adult relative intrinsic clearance per mg of hepatic microsomal protein, based on
      the deconvolution of in vivo pharmacokinetic data and by accounting for the
      impact of known clinical condition on hepatic unbound intrinsic clearance for
      caffeine and theophylline as markers of CYP1A2 activity and for midazolam as a
      marker of CYP3A4 activity. RESULTS: The function for CYP1A2 describes an increase
      in relative intrinsic metabolic clearance from birth to 3 years followed by a
      decrease to adult values. The function for CYP3A4 describes a continuous rise in
      relative intrinsic metabolic clearance, reaching the adult value at about 1.3
      years of age. The new models were validated by showing improved predictions of
      the systemic clearances of ropivacaine (major CYP1A2 substrate; minor CYP3A4
      substrate) and alfentanil (major CYP3A4 substrate) compared with those using a
      previous ontogeny function based on in vitro data (alfentanil: mean squared
      prediction error 3.0 vs. 6.8; ropivacaine: mean squared prediction error 2.3
      vs.14.2). CONCLUSIONS: When implementing enzyme ontogeny functions, it is
      important to consider potential confounding factors (e.g. disease) that may
      affect the physiological conditions of the patient and, hence, the prediction of
      net in vivo clearance.

PMID- 24671885
TI  - The role of digitalis pharmacokinetics in converting atrial fibrillation and
      flutter to regular sinus rhythm.
AB  - This report examined the role of digitalis pharmacokinetics in helping to guide
      therapy with digitalis glycosides with regard to converting atrial fibrillation
      (AF) or flutter to regular sinus rhythm (RSR). Pharmacokinetic models of
      digitoxin and digoxin, containing a peripheral non-serum effect compartment, were
      used to analyze outcomes in a non-systematic literature review of five clinical
      studies, using the computed concentrations of digitoxin and digoxin in the effect
      compartment of these models in an analysis of their outcomes. Four cases treated
      by the author were similarly examined. Three literature studies showed results no
      different from placebo. Dosage regimens achieved <=11 ng/g in the model's
      peripheral compartment. However, two other studies achieved significant
      conversion to RSR. Their peripheral concentrations were 9-14 ng/g. In the four
      patients treated by the author, three converted using classical clinical
      titration with incremental doses, plus therapeutic drug monitoring and
      pharmacokinetic guidance from the models for maintenance dosage. They converted
      at peripheral concentrations of 9-18 ng/g, similar to the two studies above. No
      toxicity was seen. Successful maintenance was achieved, using the models and
      their pharmacokinetic guidance, by giving somewhat larger than average
      recommended dosage regimens in order to maintain peripheral concentrations
      present at conversion. The fourth patient did not convert, but only reached
      peripheral concentrations of 6-7 ng/g, similar to the studies in which conversion
      was no better than placebo. Pharmacokinetic analysis and guidance play a highly
      significant role in converting AF to RSR. To the author's knowledge, this has not
      been specifically described before. In my experience, conversion of AF or flutter
      to RSR does not occur until peripheral concentrations of 9-18 ng/g are reached.
      Results in the four cases correlated well with the literature findings. More work
      is needed to further evaluate these provocative findings.

PMID- 24671886
TI  - A new toolkit for conducting clinical trials in rare disorders.
AB  - Evidence based medicine requires strong scientific evidence upon which to base
      treatment. Because the available study populations for rare diseases are small,
      this evidence is difficult to accrue. Investigators need to consider a flexible
      toolkit of methods to deal with the problems inherent in the study of rare
      disease. We present some potential solutions in this paper. 

PMID- 24671887
TI  - [Development of a Checklist to Assess School Smoking Policy].
AB  - The school system is an established setting for behavioural and environmental
      tobacco prevention activities. Most research on the effectiveness of tobacco
      prevention has been conducted with regard to behavioural approaches, knowledge
      about school smoking policy is lacking. This research project aimed at developing
      a psychometrically sound instrument to assess school smoking policy. The
      checklist presented here contains five scales with a total of 15 items. Its
      reliability was tested with 42 Bavarian schools and 607 schools from Hesse. The
      checklist allows to measure school smoking policy in a reliable and action
      oriented manner. 

PMID- 24671888
TI  - [OptimaHl 60plus--Development, Implementation and Transfer of a Counselling Aid
      for Elderly People through Participation].
AB  - One aim of the intervention study is the participatory development of a health
      related counselling instrument using focus groups. The developed instrument is
      reduced to a limited number of health messages and easy to handle for elderly
      persons. A survey among General Practitioners and nursing services revealed that
      73.4% can imagine using the instrument in their daily work. When developing such
      an intervention instrument, the target groups should participate to increase its
      empowerment and sustainability. 

PMID- 24671889
TI  - [Health and Prevention Behaviour of Persons with and without Migration
      Background].
AB  - Based on a sample of the Hannover registration office this project analyses the
      health and prevention behaviour of Russian- and Turkish-language migrants
      compared to natives. The project analysis revealed considerable differences,
      particularly concerning addiction behaviour and physical activities. 

PMID- 24671890
TI  - [GeKo KidS--Health Literacy in School Children].
AB  - The main goal of this study was the evaluation of an intervention programme for
      the promotion of health literacy in school-aged children (grade 5-6). The project
      and the programme were highly accepted, the extension of the annual dental health
      examination was suitable to collect data within evaluation projects in schools.
      In spite of positive outcomes, a longer supervision phase would be necessary in
      order to optimise and to implement other programme components fully. 

PMID- 24671891
TI  - [General practitioners' perspectives on the planned screening programme for colon
      cancer--a general opinion].
AB  - Group discussions with family doctors (FD) about the planned nationwide screening
      programme for colorectal cancer showed that FD would appreciate knowing about the
      cost-benefit ratio of the programme before taking on a role in it.

PMID- 24671892
TI  - [Gaucher's disease and imiglucerase in 2009/2010: what leads to a suddenly
      enforced prioritisation?].
AB  - Gaucher's disease is, when left untreated, a progressive and in some subsets even
      life-threatening lysosomal storage disease. It is caused by a genetically linked
      deficit of acid beta-glucocerebrosidase. The enzyme can be replaced by
      Cerezyme((r))/imiglucerase produced by Genzyme Corp. The therapy has the
      potential to induce remis-sion and normalise the patient's life. In June 2009
      Genzyme had to announce a viral contamination of its bioreactors which led to a
      sudden stop of the entire production of imiglucerase. Subsequently only 50-20% of
      the former supply could be provided worldwide. The situation was not normalised
      until the beginning of the year 2011. Due to this unexpected shortage the
      relevant actors had to clarify quickly and unprepared which patient groups to
      prioritise and whom to supply with what quantities of imiglucerase. The shortly
      enforced prioritisation and rationing provide an opportunity to describe and
      analyse the spontaneously choosen prioritisation criteria and reveal value
      preferences shared by clinicians, patients, patient representatives, and company
      representatives. To reconstruct the chain of events and reactions and the
      revealed criteria and value preferences partly standardised interviews with
      representatives of the relevant stakeholder groups were conducted. Very clearly,
      the actors spontaneously chose to follow a medical need and a social solidarity
      principle. 

PMID- 24671893
TI  - [Health care for undocumented migrants--a quantitative study on the role of local
      health authorities in Germany].
AB  - Public welfare on a municipal level for groups with special health risks has been
      an important topic of public health service for more than a century. This notion
      has been taken up by the German "Protection against Infection Act" (IfSG) in S 19
      IfSG. Local health service authorities may provide out-patient treatment in
      addition to counselling and diagnosis for patients with sexually transmitted
      infections and tuberculosis, which is covered by public resources in cases of
      apparent need. Due to altered legislation and increased global mobility, this may
      become important for migrants without access to regular health care.Aims of this
      study were recording, counselling, diagnosis and out-patient treatment of
      migrants without legal residence status under the German Protection against
      Infection Act in the public health care system.An electronic mail survey of all
      local health authorities (n=384) by means of a standardised questionnaire was
      undertaken. Data were analysed using descriptive statistics. In the annex of the
      questionnaire the participants were asked to describe a case study.139 of 384
      local health authorities completed the questionnaire (36.2%) of whom
      approximately a quarter (24.6%) described contacts to "illegal" migrants.
      Contacts to migrants without legal residence status are more frequent in cities
      with more than 100,000 inhabitants than in ismaller cities (p<0.05). 22.6% of all
      local health authorities make an effort to reach undocumented migrants for
      counseling and diagnosis. 25 of the local health authorities (18.4%) indicated
      the capability to provide treatment in accordance with S 19 IfSG. A majority of
      these local health authorities also have contacts to undocumented migrants (75%).
      16 local health authorities (13.3%) provide out-patient treatment for diseases
      not listed in Protection against Infection Act. 56 authorities (46.7%) refer
      patients to aid organisations or to resident doctors.Only a small number of local
      health authorities have contacts to migrants without health insurance. The option
      al out-patient treatment is provided by few local health authorities especially
      in cases of sexual transmitted diseases except for HIV/AIDS. In most cases
      undocumented migrants are only one group among others. The large number of cases
      in cities with more than 500,000 inhabitants shows the massive requirements.

PMID- 24671894
TI  - [Statement of the Professional Committee on Psychiatry of BVOGD on the Amendment
      of the PsychKGs of the Federal States].
AB  - It is strongly recommended to establish mental health laws in every state. By
      these laws, outpatient services have to be dedicated to avoiding involuntary
      hospitalisations. Community mental health systems need to be enabled to supply
      low threshold, immediate care services, if necessary at home (home treatment
      resp. assertive community treatment). To this end, the role of sociopsychiatric
      services in service coordination has to be strengthened and comprehensive
      community mental health organisations have to be established in every city or
      county. At state level, Councils on Mental Health need to be implemented by state
      government, mental health reporting, especially on rates of involuntary
      hospitalisations (by federal as well as state law) has to be established and
      visiting committees need to extend their scope to all institutions and services
      that play a role in prevention or aftercare of involuntary hospitalisation.

PMID- 24671895
TI  - Nanomedicine I: In vitro and in vivo evaluation of paclitaxel loaded poly
      (epsilon-caprolactone), poly (DL-lactide-co-glycolide) and poly (DL-lactic acid)
      matrix nanoparticles in wistar rats.
AB  - Progress in nanoscience and nanotechnology laid foundation for nanotherapy-based
      approach in cancer drug delivery for improved therapy and quality of life. The
      prepared polymeric nanoparticles (PNPs), PCL, PLGA and PLA NPs help in delivering
      paclitaxel (TAX) in vivo by avoiding the use of unsafe excipient, Cremophore EL.
      The classy microscopic examination SEM, TEM and AFM analysis revealed the
      spherical and smooth structure of the NPs as well as their homogeneous solid
      matrix without any amorphous arrangements. The FTIR analysis of PNPs exposed that
      there was no chemical interaction between polymer, stabilizer and TAX. The (1)H
      NMR and XRD analyses illustrate molecular dispersion of TAX in the polymeric
      matrix and no evidence was observed for the presence of crystalline TAX. The
      outcome of in vivo acute toxicity study endorses residual solvent free PNPs. The
      PNPs demonstrate excellent control in delivering TAX up to 48 h with best fitted
      to First-order, Baker-Lonsdale, Higuchi and Korsmeyer-Peppas model. The log
      plasma concentration-time profile shows that the prepared PNPs were safe and have
      much less side-effects. The pharmacokinetic study results illustrate increase in
      mean residence time as result of long circulating nature of the prepared
      nanoparticles, which helps them to reach target area. The estimated
      pharmacokinetic parameters AUC0-infinity (ng h)/mL, AUMC0-infinity (ng h(2))/mL,
      C max (ng/mL), t 1/2 (h), MRT (h), Cl (L/h/kg), V ss (L/kg) and V z (L/kg) shows
      improved therapeutic efficacy when compared with TAX solution. 

PMID- 24671896
TI  - Internet use and depression among retired older adults in the United States: a
      longitudinal analysis.
AB  - OBJECTIVES: The purpose of this study is to examine the association between
      Internet use among retired older adults in the United States and changes in a
      commonly used predictor of depression (the CES-D). METHOD: Analyzing data from
      four waves (2002-2008) of the Health and Retirement Survey, we assess whether an
      available and commonly used index of a depression state was affected by prior
      values of the index and Internet use. The sample includes 3,075 respondents
      observed over 4 waves of data, yielding a total of 12,300 observations. We
      analyzed the effect on depression of Internet use and past depression in a full
      sample and a matched sample. We also conducted informal tests for confounders.
      Finally, we tested a basic mediation model to determine whether Internet use
      affected depression through its relationship with loneliness and social
      isolation. RESULTS: Across methods, we found a positive contribution of Internet
      use to mental well-being of retired older adults in the United States, where
      Internet use reduced the probability of a depression state by one third. We found
      no evidence of confounding. Some evidence of mediation was found. DISCUSSION: Our
      dynamic probit model indicates that for retired older adults in the United
      States, Internet use was found to reduce the probability of a depressed state by
      about 33%. Number of people in the household partially mediates this
      relationship, with the reduction in depression largest for people living alone.
      This provides some evidence that the mechanism linking Internet use to depression
      is the remediation of social isolation and loneliness. Encouraging older adults
      to use the Internet may help decrease isolation and depression.

PMID- 24671897
TI  - Trying to predict the unpredictable: Variations in device-based daily monitored
      diagnostic parameters can predict malignant arrhythmic events in patients
      undergoing cardiac resynchronization therapy.
AB  - BACKGROUND: The aim of this study was to evaluate the value of device-based
      diagnostic parameters in predicting ventricular arrhythmias in cardiac
      resynchronization therapy (CRT) recipients. METHODS: Ninety-six CRT-D patients
      participating in TRUST CRT Trial were analyzed. The inclusion criteria were:
      heart failure in NYHA >= 3 class, QRS >= 120 ms, LVEF L 35% and significant
      mechanical dyssynchrony. Patients were divided into those with (n = 31, 92
      arrhythmias) and without (n = 65) appropriate ICD interventions within follow-up
      of 12.03 +/- 6.7 months. Daily monitored device-based parameters: heart rate
      (HR), thoracic impedance (TI), HR variability and physical activity were analyzed
      in 4 time windows: within 10, 7, 3 days and 1 day before appropriate ICD
      interventions. RESULTS: A consistent pattern of changes in three monitored
      factors was observed prior to arrhythmia: 1) a gradual increase of day HR (from
      103.43% of reference within 10-day window to 105.55% one day before, all p < 0.05
      vs. reference); 2) variations in night HR (104.75% in 3 days, 107.65% one day
      before, all p < 0.05) and 3) TI decrease (from 97.8% in 10 days to 96.81% one day
      before, all p < 0.05). The combination of three parameters had better predictive
      value, which improved further after exclusion of patients with atrial
      fibrillation (AF). The predictive model combining HR and TI together with LVEF
      and NT-proBNP was more prognostic than the model involving LVEF and NT-proBNP
      alone (difference in AUC 0.05, 95% CI 0.0005-0.09, p = 0.04). CONCLUSIONS: Daily
      device-monitored parameters show significant variations prior to ventricular
      arrhythmia. Combination of multiple parameters improves arrhythmia predictive
      performance by its additive value to baseline risk factors, while presence of AF
      diminishes it.

PMID- 24671898
TI  - Levels of anxiety and depression as predictors of mortality following myocardial
      infarction: A 5-year follow-up.
AB  - BACKGROUND: Post-myocardial infarction (MI) depression is a highly prevalent
      disorder, affecting nearly 18% of all MI patients, and it is a major predictor of
      disability in the year post-MI. We sought to expand this analysis by: comparing
      case-level anxiety, depression, and comorbid anxiety and depression as predictors
      of long term mortality during a 5-year follow-up period after MI; and
      investigating the role of potential modifying and confounding factors. METHODS: A
      total of 285 patients were screened on average 6 days after their MI and a 5-year
      survival rate was ascertained. The Beck Depression Inventory (BDI) and the State
      Trait Anxiety Inventory (STAI) were completed by patients hospitalized for MI. In
      addition we tested the BDI * STAI interaction effect. RESULTS: During the 5 years
      of follow-up, cardiac mortality was assessed in 274 of 285 eligible patients. Of
      the 274 patients whose survival data were available, 91 (33.2%) died. At entry,
      BDI score of 192 (67.4%) patients was >= 10 and 145 (50.9%) patients had STAI
      score >= 40. Anxiety was not associated with mortality, whereas depression
      significantly predicted death, but this association was attenuated to non
      significance with full adjustment with disease severity and confounders.
      CONCLUSIONS: Depression following MI does not predict longer-term survival with
      full adjustment.

PMID- 24671899
TI  - Newly impaired glucose metabolism and prognosis after percutaneous
      revascularization.
AB  - BACKGROUND: Clinical practice guidelines recommend ad hoc screening of diabetes
      in patients admitted for macrovascular disease; however, these recommendations
      are rarely followed in real practice. This study was undertaken to assess whether
      impaired glucose metabolism, newly diagnosed after percutaneous coronary
      intervention (PCI) or known diabetes, provides prognostic information. METHODS:
      We studied 374 patients who underwent PCI. An oral glucose tolerance test was
      carried out in the known non-diabetic patients with fasting glucose < 7 mmol/L.
      RESULTS: Eighty-one percent of the patients presented impaired glucose
      metabolism, from which 35.3% were previously diagnosed with diabetics, 21.4% were
      newly detected diabetics, and 24.3% were pre-diabetics. After a mean follow-up of
      35.8 +/- 13.4 months, only a known history of diabetes was an independent
      predictor of revascularization (OR = 2.03, p = 0.025), non-fatal acute myocardial
      infarction (OR = 2.70, p = 0.029) and readmission due to heart failure during the
      follow-up (OR = 3.82, p = 0.022). CONCLUSIONS: Screening for impaired glucose
      metabolism after PCI permits the detection of a high proportion of patients with
      abnormal glucose regulations. However, previously known diabetes remains the only
      independent predictor of cardiovascular events in the follow-up.

PMID- 24671900
TI  - Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of
      acute coronary syndrome and maintains its antiplatelet potency at 30-day follow
      up.
AB  - BACKGROUND: The aim of this study was to assess antiplatelet effect of prasugrel
      in acute coronary syndrome (ACS) patients with high on-treatment platelet
      reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention
      (PCI). METHODS: A prospective, platelet reactivity-guided, parallel-group, open
      label study including 71 patients pretreated with clopidogrel 600 mg and assigned
      either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or
      clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance
      dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)
      assessed platelet reactivity index (PRI; > 50% vs. <= 50%) measured next morning
      post-PCI. RESULTS: Median PRI value after switch to prasugrel sharply declined at
      24 h (70.0 [61.3-75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but
      significantly rose between 24 h and 30 days (27.9 [15.5-46.8]%; p < 0.0006). In
      contrast, median PRI values in the clopidogrel group were similar at baseline and
      at 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8]%; p = NS) and then modestly rose
      at 30 days (30.3 [20.4-45.7]%; p < 0.03). The prevalence of HTPR decreased in the
      prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p <
      0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both
      groups, so were the tendencies in patterns of platelet inhibition evaluated with
      multiple electrode aggregometry as compared with the VASP assay. CONCLUSIONS: Our
      study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase
      of interventionally treated ACS and maintains its antiplatelet potency in 30-day
      follow-up. Potential clinical benefits of personalized antiplatelet prasugrel
      based therapy warrant further investigation in clinical ACS trials.

PMID- 24671901
TI  - Relationships between P wave dispersion, atrial electromechanical delay, left
      atrial remodeling, and NT-proBNP levels, in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: We evaluated the associations among the well-known atrial
      fibrillation (AF) predictors including P-wave dispersion (PWD), intra- and inter
      atrial electromechanical dyssynchrony (EMD), left atrial (LA) phasic functions,
      and plasma N-terminal prohormone of B-type natriuretic peptide (NT-proBNP)
      levels, in patients with hypertrophic cardiomyopathy (HCM). METHODS: Seventy
      patients with HCM and age and sex matched 70 subjects were enrolled. PWD, LA
      total emptying fraction (LATEFr), active emptying fraction (LAAEFr), passive
      emptying fraction (LAPEFr), expansion index (LAEI) intra- and inter-atrial EMD
      were calculated. Levels of NT-proBNP of all subjects were determined. RESULTS:
      Higher PWD (p = 0.006), significantly decreased LAEI (p < 0.001), LATEFr, and
      LAPEFr (both p values < 0.001) values and significantly increased inter-atrial (p
      < 0.001), LA (p = 0.001), and right atrial dyssynchrony (p < 0.001) were observed
      in the HCM group compared to controls. PWD was negatively correlated with LAEI (r
      = -0.236, p = 0.005) and LATEFr (r = -0.242, p = 0.04), however not with LAPEFr
      (p = 0.7), or LAAEFr (p = 0.3). Except for the LA lateral wall PA' (r = 0.283, p
      = 0.02), PWD was not correlated with any atrial EMD parameter. Inter-atrial
      dyssynchrony was related to LAEI (r = -0.272, p = 0.001), LATEFr (r = -0.256, p =
      0.03), and LAPEFr (r = -0.332, p = 0.006), but not, however, to LAAEFr (p = 0.4).
      The plasma NT-proBNP levels of patients were not correlated with either PWD (p =
      0.927) or inter-atrial dyssynchrony (p = 0.102). CONCLUSIONS: PWD and inter
      atrial dysynchrony seem to independently promote AF, although both are associated
      with LA reservoir function in HCM populations. The NT-proBNP level is not
      associated with these two AF predictors in patients with HCM. NT-proBNP seems to
      be a poor marker of atrial electrical remodeling in HCM patients.

PMID- 24671902
TI  - Increased mean platelet volume in patients with infective endocarditis and
      embolic events.
AB  - BACKGROUND: Platelet activation appears to play an important role in
      thromboembolic complications of infective endocarditis (IE). Mean platelet volume
      (MPV) is a potentially useful marker of platelet activity and a quick and easy
      determinant of thrombotic risk. Hence the aim of this study was to investigate
      the baseline platelet volume indices (MPV and platelet distribution width [PDW])
      in IE patients who developed embolic events in the follow-up period and who did
      not. METHODS: The study group consisted of 76 consecutive patients (female: 55,
      male: 21, mean age: 26 years old, ranged: 8-64 years) with definite IE according
      to Duke Criteria. Thirty four healthy subjects, who were age and gender adjusted,
      served as the control group. The mean duration of hospital stay was 44 days.
      RESULTS: Among the IE patients, 13 (13/76, 17.1%) had major embolic events.
      Significantly larger vegetations were observed in patients with embolic events as
      compared to non-embolic group (1.4 vs. 1.0 cm, p = 0.03). MPV at hospital
      admission was higher in patients who had embolic events in the follow-up period
      compared to both those who did not and the control subjects (10.62 +/- 1.13 vs.
      9.25 +/- 0.97 and 8.93 +/- 0.82 fL, p < 0.001, respectively). Similarly, the
      patients with embolic events had increased PDW compared to the non-embolic ones
      and the control group (16.31 +/- 2.42 vs. 14.35 +/- 1.97 and 14.04 +/- 1.82%, p <
      0.001, respectively). CONCLUSIONS: The present study demonstrated that IE
      patients with embolic events had increased MPV and PDW values, compared to non
      embolics. Future prospective studies with standardized measurements may clarify
      the clinical role of platelet volume indices in thrombo-embolic complications of
      IE.

PMID- 24671903
TI  - The ratio of contrast volume to glomerular filtration rate predicts in-hospital
      and six-month mortality in patients undergoing primary angioplasty for ST
      elevation myocardial infarction.
AB  - BACKGROUND: The aim of this study is to determine the impact of ratio of contrast
      volume to glomerular filtration rate (V/GFR) on development of contrast-induced
      nephropathy (CIN) and long-term mortality in patients with ST-segment elevation
      acute myocardial infarction (STEMI) undergoing primary percutaneous coronary
      intervention (PCI). METHODS: A total of 645 patients with STEMI undergoing
      primary PCI was prospectively enrolled. CIN was defined as an absolute increase
      in serum creatinine > 0.5 mg/dL or a relative increase > 25% within 48 h after
      PCI. The study population was divided into tertiles based on V/GFR. A high V/GFR
      was defined as a value in the third tertile (> 3.7). RESULTS: Patients in tertile
      3 were older, had higher rate of smoking, diabetes mellitus and CIN, lower left
      ventricular ejection fraction, hemoglobin, and systolic and diastolic blood
      pressure compared to tertiles 1 and 2 (p < 0.05). V/GFR was found an independent
      predictor of in-hospital and 6-month mortality. We found 2 separate values of
      V/GFR for 2 different end points. While the ratio of 3.6 predicted in-hospital
      mortality with 78% sensitivity and 82% specificity, the ratio of 3.3 predicted 6
      month mortality with 71% sensitivity and 76% specificity. Survival rate decreases
      as V/GFR increases both for in-hospital and during 6-month follow-up. Diabetes
      mellitus and multivessel disease were other predictors of in-hospital mortality.
      CONCLUSIONS: High V/GFR level is associated with increased in-hospital and long
      term mortality in patients with STEMI undergoing primary PCI.

PMID- 24671905
TI  - A new toolkit for conducting clinical trials in rare disorders: will this dog
      hunt?

PMID- 24671904
TI  - Elevated plasma dimethylglycine is a risk marker of mortality in patients with
      coronary heart disease.
AB  - AIM: To investigate whether plasma dimethylglycine was associated with and
      improved risk prediction of mortality among patients with coronary heart disease
      (CHD). METHODS: By Cox modelling, we explored the association between plasma
      dimethylglycine and mortality in two independent cohorts of patients with
      suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction
      (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding
      plasma dimethylglycine to established CHD risk factors. RESULTS: Median follow-up
      time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across
      both cohorts, elevated plasma dimethylglycine levels were linearly associated
      with increased risk of all-cause mortality (age and gender adjusted hazard ratios
      (95% confidence interval, CI) were 1.72 (1.21-2.46) and 1.76 (1.42-2.18) when
      comparing the fourth versus the first plasma dimethylglycine quartile in patients
      with SAP and AMI, respectively). There was a particularly strong risk association
      between plasma dimethylglycine and cardiovascular, as compared with non
      cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94
      (1.21-3.11) and 1.43 (0.83-2.47) among patients with SAP and 1.97 (1.50-2.59) and
      1.44 (1.02-2.04) among patients with AMI, respectively). The relationship between
      dimethylglycine and all-cause and cardiovascular mortality was only slightly
      attenuated in analyses adjusted for established CHD risk factors. Plasma
      dimethylglycine also improved risk prediction for all-cause and cardiovascular
      mortality, and especially among patients with AMI. CONCLUSIONS: Elevated plasma
      dimethylglycine was associated with and improved risk prediction of mortality in
      patients with suspected or verified CHD. This relationship was stronger for death
      from cardiovascular, as compared with non-cardiovascular, causes.

PMID- 24671907
TI  - Delta-9-tetrahydrocannabinol/cannabidiol (Sativex(r)): a review of its use in
      patients with moderate to severe spasticity due to multiple sclerosis.
AB  - Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex(r)] is an
      oromucosal spray formulation that contains principally THC and CBD at an
      approximately 1:1 fixed ratio, derived from cloned Cannabis sativa L. plants. The
      main active substance, THC, acts as a partial agonist at human cannabinoid
      receptors (CB1 and CB2), and thus, may modulate the effects of excitatory
      (glutamate) and inhibitory (gamma-aminobutyric acid) neurotransmitters. THC/CBD
      is approved in a number of countries, including Germany and the UK, as an add-on
      treatment for symptom improvement in adult patients with moderate to severe
      spasticity due to multiple sclerosis who have not responded adequately to other
      anti-spasticity medication and who demonstrate clinically significant improvement
      in spasticity-related symptoms during an initial trial of therapy. In the largest
      multinational clinical trial that evaluated the approved THC/CBD regimen in this
      population, 12 weeks' double-blind treatment with THC/CBD significantly reduced
      spasticity severity (primary endpoint) compared with placebo in patients who
      achieved a clinically significant improvement in spasticity after 4 weeks' single
      blind THC/CBD treatment, as assessed by a patient-rated numerical rating scale. A
      significantly greater proportion of THC/CBD than placebo recipients achieved a >=
      30% reduction (a clinically relevant reduction) in spasticity severity. The
      efficacy of THC/CBD has been also shown in at least one everyday clinical
      practice study (MOVE 2). THC/CBD was generally well tolerated in clinical trials.
      Dizziness and fatigue were reported most frequently during the first 4 weeks of
      treatment and resolved within a few days even with continued treatment. Thus, add
      on THC/CBD is a useful symptomatic treatment option for its approved indication.

PMID- 24671908
TI  - Elvitegravir: a review of its use in adults with HIV-1 infection.
AB  - The HIV integrase inhibitor elvitegravir is now available as a single-agent
      tablet (Vitekta((r))) in the EU, where it is indicated for once-daily oral use,
      in combination with a ritonavir-boosted protease inhibitor (PI) and other
      antiretrovirals, for the treatment of HIV-1 infection in adults without known
      mutations associated with resistance to elvitegravir. The drug has potent anti
      HIV activity and a well characterized resistance profile, although cross
      resistance with raltegravir is observed. When used in combination with ritonavir
      boosted PI-based antiretroviral therapy (ART) in treatment-experienced adults in
      a randomized, double-blind, phase III trial, once-daily elvitegravir was
      associated with virological suppression noninferior to that seen with twice-daily
      raltegravir after 48 weeks' treatment, and such benefits were largely maintained
      at 96 weeks. Moreover, in an open-label extension of this study, in which all
      patients received an elvitegravir regimen, virological suppression continued to
      be observed in most patients at 144 weeks. Elvitegravir is generally well
      tolerated, with diarrhoea and nausea being the most common tolerability issues.
      Thus, single-agent elvitegravir extends the treatment options available for use
      in the ritonavir-boosted PI-based ART regimens of adults infected with HIV-1 and
      has the convenience of once-daily administration. 

PMID- 24671909
TI  - The estimation of direct and indirect causal effects in the presence of
      misclassified binary mediator.
AB  - Mediation analysis serves to quantify the effect of an exposure on an outcome
      mediated by a certain intermediate and to quantify the extent to which the effect
      is direct. When the mediator is misclassified, the validity of mediation analysis
      can be severely undermined. The contribution of the present work is to study the
      effects of non-differential misclassification of a binary mediator in the
      estimation of direct and indirect causal effects when the outcome is either
      continuous or binary and exposure-mediator interaction can be present, and to
      allow the correction of misclassification. A hybrid of likelihood-based and
      predictive value weighting method for misclassification correction coupled with
      sensitivity analysis is proposed and a second approach using the expectation
      maximization algorithm is developed. The correction strategy requires knowledge
      of a plausible range of sensitivity and specificity parameters. The approaches
      are applied to a perinatal epidemiological study of the determinants of pre-term
      birth. 

PMID- 24671910
TI  - Diminished serum paraoxonase activity in patients with coronary artery
      calcification.
AB  - BACKGROUND: Previous studies have shown an association between paraoxonase (PON)
      activity and the presence and severity of coronary atherosclerosis. AIM: To
      demonstrate any association between serum PON activity and the presence and
      severity of coronary artery calcification (CAC). METHODS: A total of 156
      consecutive patients having the suspicion of coronary atherosclerosis or needing
      risk stratification for cardiovascular events were included in the present study.
      Peripheral venous blood samples of all participants to measure serum PON activity
      were collected before undergoing multidetector computed tomography, which was
      used to determine the presence and quantity of CAC. RESULTS: Serum PON-1 levels
      were lower in the CAC group compared to the no CAC group (60 [35-96] U/L vs. 291
      [230-371] U/L, respectively, p < 0.001). There was a significant negative
      correlation between total CAC score and PON (r2 = 0.335, p < 0.001). In
      multivariate analysis, the significant and independent predictors of the presence
      of CAC were male sex, high-sensitive C-reactive protein, and PON. Similarly,
      increased PON was significantly and independently associated with freedom from
      CAC. In receiver operating characteristics analysis, PON level < 197 U/L had 87%
      sensitivity, 91% specificity, 93% positive predictive value, and 85% negative
      predictive value in predicting CAC. CONCLUSIONS: Diminished serum PON activity is
      significantly and independently associated with the presence and severity of CAC,
      and vice versa.

PMID- 24671911
TI  - Readmission to an intensive care unit after cardiac surgery: reasons and
      outcomes.
AB  - BACKGROUND: Intensive care unit (ICU) readmission after cardiac surgery is
      believed to be associated with higher in-hospital mortality and may predict poor
      outcomes. ICU readmissions use resources and increase treatment costs. AIM: To
      determine reasons for readmission to ICU, evaluate outcomes in these patients,
      and identify factors predisposing to the need for readmission to ICU. METHODS: We
      retrospectively investigated a total of 2076 consecutive adult patients who
      underwent either isolated coronary artery bypass grafting or a valve procedure or
      combination of both and were discharged from our ICU between January 2008 and
      December 2010. To identify the factors that increase the risk of readmission to
      ICU, we used the dominance-based rough set approach (DRSA) which is a methodology
      of knowledge discovery from data. The knowledge has the form of "if... then..."
      decision rules relating patient characteristics to the risk of readmission to
      ICU. RESULTS: Of 2076 patients discharged from ICU, 56 (2.7%) required a second
      stay in the ICU (study group) while 2020 patients needed no readmission to ICU
      (control group). The main causes of readmission were haemodynamic instability
      (28.6%, n = 16), respiratory failure (23.2%, n = 13), and cardiac tamponade or
      bleeding (23.2%, n = 13). The mean length of stay (LOS) in the general cardiac
      ward after primary discharge from ICU until readmission was 3.5 +/- 4.2 days. The
      mean LOS in ICU after readmission was 12.5 +/- 21.2 days. Postoperative
      complications occurred more frequently in readmitted patients (10.2% vs. 48.2%, p
      < 0.0001). In-hospital mortality was significantly higher in the study group (15
      [26.8%] vs. 23 [1.1%] patients, p < 0.0001). As a result of applying the DRSA
      methodology, the algorithm generated decision rules categorizing patients into
      high and low ICU readmission risk. Advanced age, non-elective surgery and the
      length of initial ICU stay after the surgery were the factors of greatest
      importance for the correct categorisation of patients in the study group.
      CONCLUSIONS: The most common cause of readmission to ICU is haemodynamic
      instability. Postoperative complication and in-hospital mortality rates are
      significantly higher in patients readmitted to ICU. Factors most commonly
      predisposing to readmission to ICU after cardiac surgery included advanced
      patient age, non-elective surgery, and longer initial stay in ICU after the
      surgery.

PMID- 24671912
TI  - Coronary artery bypass grafting in patients over 80 years of age: a single-centre
      experience.
AB  - BACKGROUND: Extended length of human life leads to an increased number of the
      elderly with coronary artery disease. Advanced age does not constitute a contra
      indication for surgical revascularisation. However, as reflected by the available
      risk scores, mortality risk associated with operating patients in the 9th decade
      of life is increased. AIM: To characterise patients over 80 years of age
      undergoing coronary artery bypass grafting (CABG) and to evaluate in-hospital
      mortality in the study group. METHODS: We retrospectively analysed medical
      records of 51 patients over 80 years of age who underwent CABG in a
      cardiacsurgical department of a regional cardiology centre in 2008-2011. The
      following factors were taken into consideration: coexisting diseases, laboratory
      test results, echocardiographic findings, surgical data, and in-hospital
      mortality. EuroSCORE (European System for Cardiac Operative Risk Evaluation) I
      and EuroSCORE II risk scores were used for preoperative risk assessment. RESULTS:
      The mean age in the study group was 81.7 years. Coexisting diseases included
      hypertension in 76.5% of patients, impaired renal function in 62.7% of patients,
      heart failure in 31.4% of patients, atrial fibrillation (AF) in 21.6% of
      patients, and diabetes mellitus in 15.7% of patients. Most patients had a history
      of myocardial infarction (MI). CABG was performed using cardiopulmonary bypass in
      51.6% of patients. The most frequent complications were new onset AF which
      occurred in 41.2% of operated patients and low cardiac output syndrome which was
      observed in 37.3% of patients. In-hospital mortality rate among patients over 80
      years of age undergoing CABG was 3.9%, lower than predicted by the logistic
      EuroSCORE I (9.1%) and EuroSCORE II (7.3%). Two patients died during the
      postoperative period, including one operated with the use of cardiopulmonary
      bypass. CONCLUSIONS: The most common concomitant conditions in the elderly
      patients undergoing cardiac surgery are hypertension and impaired renal function.
      The majority of operated patients already suffered a MI. AF and low cardiac
      output syndrome are the most common postoperative complications. Among patients
      above 80 years of age, operative mortality risk predicted using the EuroSCORE I
      and EuroSCORE II may be overestimated. Patient selection for cardiac surgery must
      be based on individual factors, taking into account the feasibility of
      postoperative rehabilitation and the potential for improved survival and quality
      of life.

PMID- 24671913
TI  - Does SYNTAX score predict in-hospital outcomes in patients with ST elevation
      myocardial infarction undergoing primary percutaneous coronary intervention?
AB  - BACKGROUND: SYNTAX score (SxS) has been demonstrated to predict long-term
      outcomes in stable patients with coronary artery disease. But its prognostic
      value for patients with acute coronary syndrome remains unknown. AIM: To evaluate
      whether SxS could predict in-hospital outcomes for patients admitted with ST
      elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary
      intervention (pPCI). METHODS: The study included 538 patients with STEMI who
      underwent pPCI between January 2010 and December 2012. The patients were divided
      into two groups: low SxS (< 22) and high SxS (> 22). The SxS of all patients was
      calculated from aninitial angiogram and TIMI flow grade of infarct related artery
      was calculated after pPCI. Left ventricular systolic functions of the patients
      were evaluated with an echocardiogram in the following week. The rates of
      reinfarction and mortality during hospitalisation were obtained from the medical
      records of our hospital. RESULTS: The high SxS group had more no-reflow (41% and
      25.1%, p < 0.001, respectively), lower ejection fraction (38.2 +/- 7.5% and 44.6
      +/- 8.8%, p < 0.001, respectively), and greater rates of re-infarction (9.5% and
      7.3%, p = 0.037, respectively) and mortality (0.9% and 0.2%, p = 0.021,
      respectively) during hospitalisation compared to the low SxS group. On
      multivariate logistic regression analysis including clinical variables, SxS was
      an independent predictor of no-reflow (OR 1.081, 95% CI 1.032-1.133, p = 0.001).
      CONCLUSIONS: SxS is a useful tool that can predict in-hospital outcomes of
      patients with STEMI undergoing pPCI.

PMID- 24671914
TI  - Short- and intermediate-term improvement of patient quality of life after
      transcatheter aortic valve implantation: a single-centre study.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a treatment option
      for elderly high-risk patients with symptomatic severe aortic stenosis.
      Improvement of quality of life (QoL) is a relevant issue in this group of
      patients. AIM: To assess changes in QoL after TAVI. METHODS: Forty patients who
      underwent TAVI in our institution were included in this QoL study. All subjects
      were screened for TAVI in a standard fashion, including QoL assessment with the
      EQoL (EQ-5D-3L). The pre- and postprocedural scores obtained up to a 12-month
      follow-up were assessed. RESULTS: Median of logistic EuroScore I was 21.5% (13.5
      26.75%), and Society of Thoracic Surgeons score was 5.5% (4.0-10.75%). Comparison
      of baseline values with follow-up data at one, six and 12 months after TAVI
      showed significant improvement of QoL (p < 0.001). Visual Analogue Scale score
      (VAS score) was assessed. There was an incremental increase in VAS score during
      follow-up (p < 0.001). Median of six-minute walk test distance at baseline was
      200 m (IQR 150-300) and 325 m (IQR 250-400) 12 months after TAVI (p < 0.001).
      CONCLUSIONS: TAVI provides improved QoL and effectively relieves symptoms.

PMID- 24671915
TI  - Type D personality and quality of life in subjects after myocardial infarction.
AB  - BACKGROUND: Type D or distressed personality, which is a combination of negative
      affectivity and social inhibition, and poor quality of life (QoL) are considered
      predictors of cardiovascular morbidity and mortality. However, little is known
      about the role of type D personality as a determinant of QoL in patients with
      cardiovascular disease. AIM: To determine the relationship between type D
      personality and QoL in patients after a myocardial infarction (MI). METHODS:
      Results obtained in 86 patients aged 36-87 (mean 60.5 +/- 10.05) years who
      suffered a MI were analysed. Most of the patients (72.1%) were men. The study
      tools included the DS-14 scale developed by Denollet to assess personality type
      and the Life Satisfaction Questionnaire by Fahrenberg et al. RESULTS: Type D
      personality was found in 46.5% of respondents. Subjects with this type of
      personality showed lower QoL compared to non-type D subjects. Among the two
      dimensions of the type D personality, social inhibition was identified as a
      predictor of poor QoL. CONCLUSIONS: Cardiac rehabilitation programs should
      include interventions to reduce features of type D personality, particularly
      social inhibition.

PMID- 24671916
TI  - Demographic and clinical characteristics of patients with atrial fibrillation and
      cardioversion as planned therapeutic options in the International Registry on
      Cardioversion of Atrial Fibrillation RHYTHM-AF Polish substudy.
AB  - BACKGROUND: Cardioversion of atrial fibrillation (AF) and maintenance of sinus
      rhythm are the basic strategies of treating AF patients. Precise data regarding
      the current practice of AF cardioversion in Europe in clinical practice is
      lacking. AIM: The primary objective of this prospective observational study was
      to characterise patients and treatment patterns in whom cardioversion was the
      planned therapeutic option. METHODS: Patients with recent onset of AF were
      included, regardless of when the timing of the cardioversion was planned. Ten
      countries participated in the study, with Poland contributing 501 patients. The
      global enrollment period lasted from May 2010 to June 2011. Follow-up data was
      collected 60 days after enrollment via a medical chart abstraction or a telephone
      interview. RESULTS: The average age of the Polish patient population was 64.2
      years, and 38.5% of patients were female. Mean duration of arrhythmia was 3.3
      years. Paroxysmal AF was diagnosed in 38.3% and persistent AF in 43.6% of
      patients. The most prevalent AF risk factors were hypertension (75.0%), diabetes
      mellitus (20.5%), and family history of AF (12.1%). Mean body mass index of study
      patients was 29.5 kg/m2. The most pertinent factors triggering AF were emotion
      (12.4%), exercise (6.5%), electrolyte disturbances (5.5%), and acute myocardial
      infarction (3.7%). Only 14.2% of patients were asymptomatic. Previous episodes of
      AF were present in 83.1% of patients and 58.5% of them had previous
      cardioversion: 49.8% pharmacological and 50.2% electrical. The most often used
      anti-arrhythmic drugs were amiodarone (53.4%) and propafenone (32.2%). The rate
      of antithrombotic treatment was low: 59.6%. Finally electrical cardioversion had
      been undergone by 165 (53%) patients and pharmacological by 146 (47%) patients.
      CONCLUSIONS: The population of patients with AF and planned cardioversion
      represented typical patients with non-valvular AF and standard symptoms, the vast
      majority of whom were symptomatic. The study group in terms of comprehensive
      characteristics is representative of the general population of AF patients.

PMID- 24671917
TI  - Obstructive sleep apnoea in patients with atrial fibrillation: prevalence,
      determinants and clinical characteristics of patients in Polish population.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) and atrial fibrillation (AF) are two
      conditions highly prevalent in the general population. OSA is known to cause
      haemodynamic changes, oxidative stress, and endothelial damage, and therefore
      promote vascular and heart remodelling which results in AF triggering and
      exacerbation. Coexistence of OSA and AF influences the course of both diseases,
      and therefore should be taken into consideration in patient management strategy
      planning. AIM: To assess the prevalence of OSA in Polish AF patients, and to
      describe the clinical characteristics of patients with concomitant OSA and AF.
      METHODS: We enrolled into the study 289 consecutive patients hospitalised in a
      tertiary, high-volume Cardiology Department with a primary diagnosis of AF. In
      addition to standard examination, all patients underwent an overnight sleep study
      to diagnose OSA, which was defined as apnoea-hypopnoea index (AHI) >= 5 per hour.
      RESULTS: After applying exclusion criteria, the final analysis covered 266
      patients (65.0% male, mean age 57.6 +/- 10.1 years). OSA was present in 121
      (45.49%) patients. Patients with OSA were older (59.6 +/- 8.0 vs. 56.0 +/- 11.4
      years; p = 0.02), had higher body mass index (BMI; 30.9 +/- 5.4 vs. 28.7 +/- 4.4
      kg/m2; p < 0.01) larger neck size (41.2 +/- 3.8 vs. 39.3 +/- 3.3 cm; p = 0.0001)
      and waist circumference (108.5 +/- 13.1 vs. 107.7 +/- 85.4 cm; p < 0.0001) than
      patients without OSA. There were no significant differences between the groups in
      terms of systolic and diastolic blood pressure or history of comorbidities (p >
      0.05). OSA patients were less likely than non-OSA patients to have paroxysmal AF
      (62.0% vs. 75.9%; p = 0.02). Dividing newly diagnosed OSA patients according to
      the disease severity showed that mild OSA (AHI >= 5/h and < 15/h) was present in
      27.82% of the study population, moderate OSA (AHI <= 15/h and >= 30/h) in 13.16%
      of patients, and severe OSA (> 30/h) in 4.51% of patients. No significant
      differences in terms of comorbidities and anthropometric features were seen
      between mild and moderate, between moderate and severe, and between mild and
      severe OSA. CONCLUSIONS: OSA is highly prevalent in patients with AF in the
      Polish population, and affects approximately half of the patients. OSA patients
      are more likely to be older, have higher BMI, and greater waist and neck
      circumference. Persistent AF is the most common form of the arrhythmia in
      patients with OSA, while patients without OSA are more likely to have paroxysmal
      AF.

PMID- 24671918
TI  - Access for percutaneous coronary intervention in ST segment elevation myocardial
      infarction: radial vs. femoral--a prospective, randomised clinical trial (OCEAN
      RACE).
AB  - BACKGROUND: Percutaneous treatment of patients with ST segment elevation
      myocardial infarction (STEMI) has become the standard and default mode of
      management as recommended by the European Society of Cardiology guidelines for
      managing acute myocardial infarction in patients presenting with STEMI. The
      choice of vascular access is made by the operator and has a potential impact on
      the safety and efficacy of the procedure and outcomes. AIM: To understand the
      influence of a radial approach on bleeding complications and angiographic
      success, we performed a prospective, controlled randomised trial. METHODS:
      Patients were allocated to radial (TR) or femoral (TF) vascular access. The
      primary endpoints were major bleeding by the REPLACE-2 scale and minor bleeding
      by the EASY scale (TR arm) or the FEMORAL scale (TF arm). Other outcomes included
      procedural data, in-hospital and long-term survival. RESULTS: There were 103
      patients analysed in total, 52 in the TR arm and 51 in the TF arm. The
      demographic and clinical baseline characteristics were well matched between the
      two study groups. The frequency of the primary endpoint was the same in both arms
      (TR: 25.0% vs. TF: 33.3%, p = 0.238). In per protocol analysis, there was a
      significant benefit of the TR approach among independent operators (17.4% vs.
      36.8%, p = 0.038). Major bleeding by the REPLACE-2 scale occurred in 4.2% of
      patients (TR: 5.8% vs. TF: 3.9%, p = 0.509). There were no differences in terms
      of the rate of major cardiac adverse events, which happened in 10.7% of the study
      population (TR: 9.6% vs. TF: 11.8%, p = 0.48). In the TF arm, there was a trend
      towards a higher risk of local bleedings (TR: 22.4% vs. TF: 37.7%, p = 0.081) and
      a significantly higher frequency of local haematoma (class III, EASY/FEMORAL)
      (TR: 0% vs. TF: 9.8%, p = 0.027). CONCLUSIONS: There were no significant
      differences between the TR and TF approaches in terms of clinical efficacy and
      patient safety. However, patients treated by independent operators might benefit
      from TR access. The overall complication risk of percutaneous coronary
      intervention treatment of STEMI patients remains low.

PMID- 24671919
TI  - Impact of serum alkaline phosphatase level on the pathophysiologic mechanism of
      contrast-induced nephropathy.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) accounts for 10% of all causes of
      hospital-acquired renal failure. It leadsto a prolonged in-hospital stay, and
      represents a powerful predictor of poor early and late outcomes. More than half
      of casesare observed after cardiovascular procedures. AIM: To determine the
      predictive value of the serum alkaline phosphatase (ALP) level in the development
      of CIN, something which has not been assessed before. METHODS: We prospectively
      evaluated a total of 430 patients with acute coronary syndrome. Patients were
      classified according to the development of CIN and both groups were compared
      statistically according to clinical, laboratory and demographic features,
      including the serum ALP level. RESULTS: CIN was observed in 20.5% of patients.
      Advanced age, male gender, elevated creatinine, uric acid and phosphate levels,
      and low glomerular filtration rate were correlated with the development of CIN.
      Correlation analysis also showed a significant association between the ALP level
      and the development of CIN (126.1 +/- 144.9 vs. 97.2 +/- 46.9, p = 0.004).
      Univariate regression analysis also showed the impact of ALP on the development
      of CIN (OR 1.004, 95% CI 1.001-1.007, p = 0.02). Conclusions: Our outcomes
      indicate a possible active role of ALP in the mechanism of CIN. An elevated ALP
      level may predict the development of CIN.

PMID- 24671920
TI  - The potential of crowdsourcing to improve patient-centered care.
AB  - Crowdsourcing (CS) is the outsourcing of a problem or task to a crowd. Although
      patient-centered care (PCC) may aim to be tailored to an individual's needs, the
      uses of CS for generating ideas, identifying values, solving problems,
      facilitating research, and educating an audience represent powerful roles that
      can shape both allocation of shared resources and delivery of personalized care
      and treatment. CS can often be conducted quickly and at relatively low cost.
      Pitfalls include bias, risks of research ethics, inadequate quality of data,
      inadequate metrics, and observer-expectancy effect. Health professionals and
      consumers in the US should increase their attention to CS for the benefit of PCC.
      Patients' participation in CS to shape health policy and decisions is one way to
      pursue PCC itself and may help to improve clinical outcomes through a better
      understanding of patients' perspectives. CS should especially be used to traverse
      the quality-cost curve, or decrease costs while preserving or improving quality
      of care. 

PMID- 24671921
TI  - Linguistic validation into 20 languages and content validity of the rheumatoid
      arthritis-specific Work Productivity and Activity Impairment questionnaire.
AB  - BACKGROUND: Impairments in work productivity and daily activities contribute to
      the burden of rheumatoid arthritis (RA). It is thus essential to use an
      instrument assessing both work and daily activity impairments when studying the
      full impact of RA on individuals. The Work Productivity and Activity Impairment
      (WPAI) questionnaire is such an instrument. OBJECTIVE: This study aims to
      linguistically validate the RA-specific WPAI (WPAI:RA) instrument in 20 new
      languages and to assess its content validity for individuals with RA. METHODS:
      The linguistic validation of the questionnaire followed a standard methodology
      that included comprehension test interviews (n = 5 individuals with RA per
      language) to assess the relevance, understanding and acceptability of the
      WPAI:RA. Content validity of the instrument was simultaneously investigated.
      RESULTS: Comprehension testing showed that the WPAI:RA questionnaire was well
      understood similarly across countries; minor changes were made to ensure fidelity
      to the original concepts and for ease of comprehension. The majority of
      interviewees (66/93) considered its content comprehensive and appropriate to
      measure their ability to work and perform daily activities. CONCLUSION: The
      WPAI:RA questionnaire is now linguistically validated in 20 new languages [Czech
      (Czech Republic), Dutch (Belgium), English (Canada and UK), French (Belgium,
      Canada and France), German (Germany), Hungarian (Hungary), Italian (Italy),
      Polish (Poland), Portuguese (Brazil), Romanian (Romania), Russian (Russia and
      Ukraine), Spanish (Argentina, Mexico, Spain and US) and Ukrainian (Ukraine)]. The
      WPAI:RA questionnaire shows good content validity. It can thus be used in multi
      country clinical trials to assess RA-related impact on the patients' ability to
      work and perform daily activities.

PMID- 24671922
TI  - Family and carer smoking control programmes for reducing children's exposure to
      environmental tobacco smoke.
AB  - BACKGROUND: Children's exposure to other people's cigarette smoke (environmental
      tobacco smoke, or ETS) is associated with a range of adverse health outcomes for
      children. Parental smoking is a common source of children's exposure to ETS.
      Older children are also at risk of exposure to ETS in child care or educational
      settings. Preventing exposure to cigarette smoke in infancy and childhood has
      significant potential to improve children's health worldwide. OBJECTIVES: To
      determine the effectiveness of interventions aiming to reduce exposure of
      children to ETS. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group
      Specialized Register and conducted additional searches of the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, EMBASE, CINAHL, ERIC,
      and The Social Science Citation Index & Science Citation Index (Web of
      Knowledge). Date of the most recent search: September 2013. SELECTION CRITERIA:
      Controlled trials with or without random allocation. Interventions must have
      addressed participants (parents and other family members, child care workers and
      teachers) involved with the care and education of infants and young children
      (aged 0 to 12 years). All mechanisms for reduction of children's ETS exposure,
      and smoking prevention, cessation, and control programmes were included. These
      include health promotion, social-behavioural therapies, technology, education,
      and clinical interventions. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed studies and extracted data. Due to heterogeneity of
      methodologies and outcome measures, no summary measures were possible and results
      were synthesised narratively. MAIN RESULTS: Fifty-seven studies met the inclusion
      criteria. Seven studies were judged to be at low risk of bias, 27 studies were
      judged to have unclear overall risk of bias and 23 studies were judged to have
      high risk of bias. Seven interventions were targeted at populations or community
      settings, 23 studies were conducted in the 'well child' healthcare setting and 24
      in the 'ill child' healthcare setting. Two further studies conducted in
      paediatric clinics did not make clear whether the visits were to well or ill
      children, and another included both well and ill child visits. Thirty-six studies
      were from North America, 14 were in other high income countries and seven studies
      were from low- or middle-income countries. In only 14 of the 57 studies was there
      a statistically significant intervention effect for child ETS exposure reduction.
      Of these 14 studies, six used objective measures of children's ETS exposure.
      Eight of the studies had a high risk of bias, four had unclear risk of bias and
      two had a low risk of bias. The studies showing a significant effect used a range
      of interventions: seven used intensive counselling or motivational interviewing;
      a further study used telephone counselling; one used a school-based strategy; one
      used picture books; two used educational home visits; one used brief intervention
      and one study did not describe the intervention. Of the 42 studies that did not
      show a significant reduction in child ETS exposure, 14 used more intensive
      counselling or motivational interviewing, nine used brief advice or counselling,
      six used feedback of a biological measure of children's ETS exposure, one used
      feedback of maternal cotinine, two used telephone smoking cessation advice or
      support, eight used educational home visits, one used group sessions, one used an
      information kit and letter, one used a booklet and no smoking sign, and one used
      a school-based policy and health promotion. In 32 of the 57 studies, there was
      reduction of ETS exposure for children in the study irrespective of assignment to
      intervention and comparison groups. One study did not aim to reduce children's
      tobacco smoke exposure, but rather aimed to reduce symptoms of asthma, and found
      a significant reduction in symptoms in the group exposed to motivational
      interviewing. We found little evidence of difference in effectiveness of
      interventions between the well infant, child respiratory illness, and other child
      illness settings as contexts for parental smoking cessation interventions.
      AUTHORS' CONCLUSIONS: While brief counselling interventions have been identified
      as successful for adults when delivered by physicians, this cannot be
      extrapolated to adults as parents in child health settings. Although several
      interventions, including parental education and counselling programmes, have been
      used to try to reduce children's tobacco smoke exposure, their effectiveness has
      not been clearly demonstrated. The review was unable to determine if any one
      intervention reduced parental smoking and child exposure more effectively than
      others, although seven studies were identified that reported motivational
      interviewing or intensive counselling provided in clinical settings was
      effective.

PMID- 24671923
TI  - Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for
      COPD: a network meta-analysis.
AB  - BACKGROUND: Pharmacological therapy for chronic obstructive pulmonary disease
      (COPD) is aimed at relieving symptoms, improving quality of life and preventing
      or treating exacerbations.Treatment tends to begin with one inhaler, and
      additional therapies are introduced as necessary. For persistent or worsening
      symptoms, long-acting inhaled therapies taken once or twice daily are preferred
      over short-acting inhalers. Several Cochrane reviews have looked at the risks and
      benefits of specific long-acting inhaled therapies compared with placebo or other
      treatments. However for patients and clinicians, it is important to understand
      the merits of these treatments relative to each other, and whether a particular
      class of inhaled therapies is more beneficial than the others. OBJECTIVES: To
      assess the efficacy of treatment options for patients whose chronic obstructive
      pulmonary disease cannot be controlled by short-acting therapies alone. The
      review will not look at combination therapies usually considered later in the
      course of the disease.As part of this network meta-analysis, we will address the
      following issues.1. How does long-term efficacy compare between different
      pharmacological treatments for COPD?2. Are there limitations in the current
      evidence base that may compromise the conclusions drawn by this network meta
      analysis? If so, what are the implications for future research? SEARCH METHODS:
      We identified randomised controlled trials (RCTs) in existing Cochrane reviews by
      searching the Cochrane Database of Systematic Reviews (CDSR). In addition, we ran
      a comprehensive citation search on the Cochrane Airways Group Register of trials
      (CAGR) and checked manufacturer websites and reference lists of other reviews.
      The most recent searches were conducted in September 2013. SELECTION CRITERIA: We
      included parallel-group RCTs of at least 6 months' duration recruiting people
      with COPD. Studies were included if they compared any of the following treatments
      versus any other: long-acting beta2-agonists (LABAs; formoterol, indacaterol,
      salmeterol); long-acting muscarinic antagonists (LAMAs; aclidinium,
      glycopyrronium, tiotropium); inhaled corticosteroids (ICSs; budesonide,
      fluticasone, mometasone); combination long-acting beta2-agonist (LABA) and
      inhaled corticosteroid (LABA/ICS) (formoterol/budesonide, formoterol/mometasone,
      salmeterol/fluticasone); and placebo. DATA COLLECTION AND ANALYSIS: We conducted
      a network meta-analysis using Markov chain Monte Carlo methods for two efficacy
      outcomes: St George's Respiratory Questionnaire (SGRQ) total score and trough
      forced expiratory volume in one second (FEV1). We modelled the relative
      effectiveness of any two treatments as a function of each treatment relative to
      the reference treatment (placebo). We assumed that treatment effects were similar
      within treatment classes (LAMA, LABA, ICS, LABA/ICS). We present estimates of
      class effects, variability between treatments within each class and individual
      treatment effects compared with every other.To justify the analyses, we assessed
      the trials for clinical and methodological transitivity across comparisons. We
      tested the robustness of our analyses by performing sensitivity analyses for lack
      of blinding and by considering six- and 12-month data separately. MAIN RESULTS:
      We identified 71 RCTs randomly assigning 73,062 people with COPD to 184 treatment
      arms of interest. Trials were similar with regards to methodology, inclusion and
      exclusion criteria and key baseline characteristics. Participants were more often
      male, aged in their mid sixties, with FEV1 predicted normal between 40% and 50%
      and with substantial smoking histories (40+ pack-years). The risk of bias was
      generally low, although missing information made it hard to judge risk of
      selection bias and selective outcome reporting. Fixed effects were used for SGRQ
      analyses, and random effects for Trough FEV1 analyses, based on model fit
      statistics and deviance information criteria (DIC). SGRQ SGRQ data were available
      in 42 studies (n = 54,613). At six months, 39 pairwise comparisons were made
      between 18 treatments in 25 studies (n = 27,024). Combination LABA/ICS was the
      highest ranked intervention, with a mean improvement over placebo of -3.89 units
      at six months (95% credible interval (CrI) -4.70 to -2.97) and -3.60 at 12 months
      (95% CrI -4.63 to -2.34). LAMAs and LABAs were ranked second and third at six
      months, with mean differences of -2.63 (95% CrI -3.53 to -1.97) and -2.29 (95%
      CrI -3.18 to -1.53), respectively. Inhaled corticosteroids were ranked fourth (MD
      -2.00, 95% CrI -3.06 to -0.87). Class differences between LABA, LAMA and ICS were
      less prominent at 12 months. Indacaterol and aclidinium were ranked somewhat
      higher than other members of their classes, and formoterol 12 mcg, budesonide 400
      mcg and formoterol/mometasone combination were ranked lower within their classes.
      There was considerable overlap in credible intervals and rankings for both
      classes and individual treatments. Trough FEV1 Trough FEV1 data were available in
      46 studies (n = 47,409). At six months, 41 pairwise comparisons were made between
      20 treatments in 31 studies (n = 29,271). As for SGRQ, combination LABA/ICS was
      the highest ranked class, with a mean improvement over placebo of 133.3 mL at six
      months (95% CrI 100.6 to 164.0) and slightly less at 12 months (mean difference
      (MD) 100, 95% CrI 55.5 to 140.1). LAMAs (MD 103.5, 95% CrI 81.8 to 124.9) and
      LABAs (MD 99.4, 95% CrI 72.0 to 127.8) showed roughly equivalent results at six
      months, and ICSs were the fourth ranked class (MD 65.4, 95% CrI 33.1 to 96.9). As
      with SGRQ, initial differences between classes were not so prominent at 12
      months. Indacaterol and salmeterol/fluticasone were ranked slightly better than
      others in their class, and formoterol 12, aclidinium, budesonide and
      formoterol/budesonide combination were ranked lower within their classes. All
      credible intervals for individual rankings were wide. AUTHORS' CONCLUSIONS: This
      network meta-analysis compares four different classes of long-acting inhalers for
      people with COPD who need more than short-acting bronchodilators. Quality of life
      and lung function were improved most on combination inhalers (LABA and ICS) and
      least on ICS alone at 6 and at 12 months. Overall LAMA and LABA inhalers had
      similar effects, particularly at 12 months. The network has demonstrated the
      benefit of ICS when added to LABA for these outcomes in participants who largely
      had an FEV1 that was less than 50% predicted, but the additional expense of
      combination inhalers and any potential for increased adverse events (which has
      been established by other reviews) require consideration. Our findings are in
      keeping with current National Institute for Health and Care Excellence (NICE)
      guidelines.

PMID- 24671924
TI  - Using the EuroQol EQ-5D in Swiss cancer patients, which value set should be
      applied?
AB  - BACKGROUND: The European Quality of Life-5 Dimensions (EQ-5D) instrument combines
      questionnaire responses into a single utility estimate using country-specific
      value sets. Countries without a national value set are advised to select one
      based on geographic proximity. In the absence of a Swiss value set, we used
      foreign value sets to gain insights into their appropriateness for use with Swiss
      cancer patients. METHODS: EQ-5D health states and visual analogue scale (VAS)
      ratings were collected in one German and three Swiss oncology trials. Utilities
      were calculated based on the United Kingdom (UK), German (GE), French (FR) and
      European Union (EU) value sets. Resulting differences and Pearson partial
      correlation coefficients with corresponding VAS ratings were assessed. RESULTS:
      In total, 202 Swiss and 154 German patients undergoing cancer treatment completed
      at least two EQ-5D forms. The mean difference between GE-based and FR-, UK- or EU
      based utilities was significantly larger than the differences between the latter.
      The absolute mean difference between utilities and VAS ratings was highest for GE
      based utilities, for Swiss (0.170, 95 % confidence interval [CI] 0.146-0.194) and
      German patients (0.174, 95 % CI 0.145-0.202). The correlation between GE-based
      utilities and VAS ratings was the lowest (r = 0.36, 95 % CI 0.33-0.40); the
      highest was between FR-based utilities and VAS ratings (r = 0.43, 95 % CI 0.39
      0.46). CONCLUSION: For Switzerland, utility calculations based on the German or
      French value set would be an obvious choice. Our results suggest that the German
      value set may not be the most appropriate for use with Swiss cancer patients. The
      French and EU value sets may be relevant alternatives and improve international
      comparability.

PMID- 24671925
TI  - Evidence of early ultrastructural photoreceptor abnormalities in light-induced
      retinal degeneration using spectral domain optical coherence tomography.
AB  - BACKGROUND: To study spatiotemporal in vivo changes in retinal morphology and
      quantify thickness of retinal layers in a mouse model of light-induced retinal
      degeneration using spectral domain optical coherence tomography (SD-OCT).
      METHODS: BALB/c mice were exposed to 5000 lux of constant light for 3 h. SD-OCT
      images were taken 3 h, 24 h, 3 days, 1 week and 1 month after light exposure and
      were compared with histology at the same time points. SD-OCT images were also
      taken at 0, 1 and 2 h after light exposure in order to analyse retinal changes at
      the earliest time points. The thickness of retinal layers was measured using the
      Bioptigen software InVivoVue Diver. RESULTS: SD-OCT demonstrated progressive
      outer retinal thinning. 3 h after light exposure, the outer nuclear layer
      converted from hyporeflective to hyper-reflective. At 24 h, outer retinal bands
      and nuclear layer demonstrated similar levels of hyper-reflectivity. Significant
      variations in outer retinal thickness, vitreous opacities and retinal detachments
      occurred within days of injury. Thinning of the retina was observed at 1 month
      after injury. It was also determined that outer nuclear layer changes precede
      photoreceptor segment structure disintegration and the greatest change in segment
      structure occurs between 1 and 2 h after light exposure. CONCLUSIONS:
      Longitudinal SD-OCT reveals intraretinal changes that cannot be observed by
      histopathology at early time points in the light injury model.

PMID- 24671926
TI  - Factors predictive of long-term visual outcomes of Group D eyes treated with
      chemoreduction and low-dose IMRT salvage: the Children's Hospital Los Angeles
      experience.
AB  - AIM: To evaluate clinical factors predictive of visual outcomes in Group D
      retinoblastoma eyes. METHODS: Retrospective chart review of patients with Group D
      retinoblastoma from January 2000 to December 2009. All patients were treated with
      systemic chemoreduction and external beam radiation as salvage therapy when
      indicated. Primary outcome measure was visual acuity. Clinical factors evaluated
      include quadrants of subretinal fluid, extent of vitreous seeding, involvement of
      more/less than 50% of the macula, endophytic/exophytic tumour classification, and
      presence of tumour behind the lens at diagnosis. RESULTS: Fifty-two Group D eyes
      of 41 patients were included; 10 eyes with visual acuity better than 20/80, 32
      eyes with vision worse than 20/100 and 10 eyes with indeterminate vision (fix and
      follow). Complete retinal detachment (p=0.002), involvement of >50% of the macula
      (p=0.01), and seeding >3 quadrants (p=0.05) were associated with worse visual
      outcome. Average follow-up was 50.0 months (range: 10-118 months). CONCLUSIONS:
      At presentation, it is difficult to predict which Group D eyes will be salvaged
      with useful vision following systemic chemotherapy. The presence of complete
      retinal detachment, macular involvement and extensive seeding on presentation
      were factors associated with a worse visual prognosis in this study. These
      findings can guide the ophthalmologist in clinical decision making, as well as in
      counselling parents.

PMID- 24671927
TI  - Are worldwide albinism prevalence figures an accurate reflection? An incidental
      finding from a Northern Ireland study.

PMID- 24671928
TI  - Biocompatible dialysis fluids for peritoneal dialysis.
AB  - BACKGROUND: The longevity of peritoneal dialysis (PD) is limited by high rates of
      technique failure, some of which stem from peritoneal membrane injury.
      'Biocompatible' PD solutions have been developed to reduce damage to the
      peritoneal membrane. OBJECTIVES: This review aimed to look at the benefits and
      harms of biocompatible PD solutions in comparison to standard PD solutions in
      patients receiving PD. SEARCH METHODS: We searched the Cochrane Renal Group's
      Specialised Register (28 February 2013), through contact with the Trials Search
      Co-ordinator using search terms relevant to this review. Studies contained in the
      Specialised Register are identified through search strategies specifically
      designed for CENTRAL, MEDLINE and EMBASE, and handsearching conference
      proceedings. SELECTION CRITERIA: All randomised controlled trials (RCTs) and
      quasi-RCTs in adults and children comparing the effects of biocompatible PD
      solutions (neutral pH, lactate-buffered, low glucose degradation product (GDP);
      neutral pH, bicarbonate (+/- lactate)-buffered, low GDP; glucose polymer
      (icodextrin)) in PD were included. Studies of amino acid-based PD solutions were
      excluded. DATA COLLECTION AND ANALYSIS: Two authors extracted data on study
      quality and outcomes (including adverse effects). The authors contacted
      investigators to obtain missing information. Summary estimates of effect were
      obtained using a random-effects model, and results were expressed as risk ratios
      (RR) and their 95% confidence intervals (CI) for categorical variables, and mean
      difference (MD) or standardised mean difference (SMD) and 95% CI for continuous
      variables. MAIN RESULTS: Thirty-six eligible studies (2719 patients) were
      identified: Neutral pH, lactate-buffered/bicarbonate (+/- lactate)-buffered, low
      GDP PD solution (24); icodextrin (12). Allocation methods and concealment were
      generally incompletely reported, and adequate in only ten studies (27.8%).
      Patients lost to follow-up ranged from 0% to 83.4%. Neutral pH, low GDP versus
      conventional glucose PD solutionBased on generally sub-optimal quality evidence,
      the use of neutral pH, low GDP PD solutions was associated with larger urine
      volumes at the end of the studies, up to three years of therapy duration (7
      studies, 520 patients: MD 126.39 mL/d, 95% CI 26.73 to 226.05). Improved
      preservation of residual renal function was evident in studies with greater than
      12 month follow-up (6 studies, 360 patients: SMD 0.31, 95% CI 0.10 to 0.52).
      There was no significant effect on peritonitis, technique failure or adverse
      events with the use of neutral pH, low GDP PD solutions. Glucose polymer
      (icodextrin) versus conventional glucose PD solutionThere was a significant
      reduction in episodes of uncontrolled fluid overload (2 studies, 100 patients: RR
      0.30, 95% CI 0.15 to 0.59) and improvement in peritoneal ultrafiltration (4
      studies, 102 patients, MD 448.54 mL/d, 95% CI 289.28 to 607.80) without
      compromising residual renal function (4 studies, 114 patients: SMD 0.12, 95% CI 
      0.26 to 0.49) or urine output (3 studies, 69 patients: MD -88.88 mL/d, 95% CI 
      356.88 to 179.12) with icodextrin use. A comparable incidence of adverse events
      with the icodextrin (four studies) was reported. AUTHORS' CONCLUSIONS: Based on
      generally sub-optimal quality studies, use of neutral pH, low GDP PD solution led
      to greater urine output and higher residual renal function after use exceeded 12
      months. Icodextrin prescription improved peritoneal ultrafiltration and mitigated
      uncontrolled fluid overload. There were no significant effects on peritonitis,
      technique survival, patient survival or harms identified with their use. Based on
      the best available evidence, the use of these 'biocompatible' PD solutions
      resulted in clinically relevant benefits without added risks of harm.

PMID- 24671929
TI  - Interventions for preoperative smoking cessation.
AB  - BACKGROUND: Smokers have a substantially increased risk of postoperative
      complications. Preoperative smoking intervention may be effective in decreasing
      this incidence, and surgery may constitute a unique opportunity for smoking
      cessation interventions. OBJECTIVES: The objectives of this review are to assess
      the effect of preoperative smoking intervention on smoking cessation at the time
      of surgery and 12 months postoperatively, and on the incidence of postoperative
      complications. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group
      Specialized Register in January 2014. SELECTION CRITERIA: Randomized controlled
      trials that recruited people who smoked prior to surgery, offered a smoking
      cessation intervention, and measured preoperative and long-term abstinence from
      smoking or the incidence of postoperative complications or both outcomes. DATA
      COLLECTION AND ANALYSIS: The review authors independently assessed studies to
      determine eligibility, and discussed the results between them. MAIN RESULTS:
      Thirteen trials enrolling 2010 participants met the inclusion criteria. One trial
      did not report cessation as an outcome. Seven reported some measure of
      postoperative morbidity. Most studies were judged to be at low risk of bias but
      the overall quality of evidence was moderate due to the small number of studies
      contributing to each comparison.Ten trials evaluated the effect of behavioural
      support on cessation at the time of surgery; nicotine replacement therapy (NRT)
      was offered or recommended to some or all participants in eight of these. Two
      trials initiated multisession face-to-face counselling at least four weeks before
      surgery and were classified as intensive interventions, whilst seven used a brief
      intervention. One further study provided an intensive intervention to both
      groups, with the intervention group additionally receiving a computer-based
      scheduled reduced smoking intervention. One placebo-controlled trial examined the
      effect of varenicline administered one week preoperatively followed by 11 weeks
      postoperative treatment, and one placebo-controlled trial examined the effect of
      nicotine lozenges from the night before surgery as an adjunct to brief
      counselling at the preoperative evaluation. There was evidence of heterogeneity
      between the effects of trials using intensive and brief interventions, so we
      pooled these separately. An effect on cessation at the time of surgery was
      apparent in both subgroups, but the effect was larger for intensive intervention
      (pooled risk ratio (RR) 10.76; 95% confidence interval (CI) 4.55 to 25.46, two
      trials, 210 participants) than for brief interventions (RR 1.30; 95% CI 1.16 to
      1.46, 7 trials, 1141 participants). A single trial did not show evidence of
      benefit of a scheduled reduced smoking intervention. Neither nicotine lozenges
      nor varenicline were shown to increase cessation at the time of surgery but both
      had wide confidence intervals (RR 1.34; 95% CI 0.86 to 2.10 (1 trial, 46
      participants) and RR 1.49; 95% CI 0.98 to 2.26 (1 trial, 286 participants)
      respectively). Four of these trials evaluated long-term smoking cessation and
      only the intensive intervention retained a significant effect (RR 2.96; 95% CI
      1.57 to 5.55, 2 trials, 209 participants), whilst there was no evidence of a long
      term effect following a brief intervention (RR 1.09; 95% CI 0.68 to 1.75, 2
      trials, 341 participants). The trial of varenicline did show a significant effect
      on long-term smoking cessation (RR 1.45; 95% CI 1.01 to 2.07, 1 trial, 286
      participants).Seven trials examined the effect of smoking intervention on
      postoperative complications. As with smoking outcomes, there was evidence of
      heterogeneity between intensive and brief behavioural interventions. In subgroup
      analyses there was a significant effect of intensive intervention on any
      complications (RR 0.42; 95% CI 0.27 to 0.65, 2 trials, 210 participants) and on
      wound complications (RR 0.31; 95% CI 0.16 to 0.62, 2 trials, 210 participants).
      For brief interventions, where the impact on smoking had been smaller, there was
      no evidence of a reduction in complications (RR 0.92; 95% CI 0.72 to 1.19, 4
      trials, 493 participants) for any complication (RR 0.99; 95% CI 0.70 to 1.40, 3
      trials, 325 participants) for wound complications. The trial of varenicline did
      not detect an effect on postoperative complications (RR 0.94; 95% CI 0.52 to
      1.72, 1 trial, 286 participants). AUTHORS' CONCLUSIONS: There is evidence that
      preoperative smoking interventions providing behavioural support and offering NRT
      increase short-term smoking cessation and may reduce postoperative morbidity. One
      trial of varenicline begun shortly before surgery has shown a benefit on long
      term cessation but did not detect an effect on early abstinence or on
      postoperative complications. The optimal preoperative intervention intensity
      remains unknown. Based on indirect comparisons and evidence from two small
      trials, interventions that begin four to eight weeks before surgery, include
      weekly counselling and use NRT are more likely to have an impact on complications
      and on long-term smoking cessation.

PMID- 24671930
TI  - Prevalence of primary tooth traumatic injuries among children in a large
      industrial centre of Russian Federation.
AB  - BACKGROUND: Recently, the number of children seeking dental care for traumatic
      tooth injuries has increased substantially. AIM: This study was aimed at
      assessing the prevalence of primary tooth traumatic injuries (PTTI) in the
      paediatric populace of Ekaterinburg, a large industrial centre of the Russian
      Federation. DESIGN: Following ethical approval, an epidemiological investigation
      of primary dentition was conducted, evaluating 1,149 children aged 6-72 months
      (males 586/1,149, 51%; females 563/1,149, 49%). The average age of subjects
      overall was 43.9 +/- 17.7 months (males 45.1 +/- 17.9 months; females 42.6 +/-
      17.4 months). RESULTS: The prevalence of PTTI among paediatric residents of this
      region was 9.75%, with uncomplicated crown fracture (36.9%) as the chief primary
      dental injury. Dental visits attributable to PTTI were most frequent in the age
      group of 25-36 months, which clearly constitutes the period of greatest
      vulnerability. CONCLUSIONS: The findings of this study suggest that PTTI is a
      critical issue in children, requiring programmes that address preventive dental
      care and adhere to established medical treatment standards.

PMID- 24671931
TI  - Characterization of microstructures using contour tree connectivity for fluid
      flow analysis.
AB  - Quantifying the connectivity of material microstructures is important for a wide
      range of applications from filters to biomaterials. Currently, the most used
      measure of connectivity is the Euler number, which is a topological invariant.
      Topology alone, however, is not sufficient for most practical purposes. In this
      study, we use our recently introduced connectivity measure, called the contour
      tree connectivity (CTC), to study microstructures for flow analysis. CTC is a new
      structural connectivity measure that is based on contour trees and algebraic
      graph theory. To test CTC, we generated a dataset composed of 120 samples and six
      different types of artificial microstructures. We compared CTC against the Euler
      parameter (EP), the parameter for connected pairs, the nominal opening dimension
      (dnom) and the permeabilities estimated using direct pore scale modelling. The
      results show that dnom is highly correlated with permeability (R2=0.91), but
      cannot separate the structural differences. The groups are best classified with
      feature combinations that include CTC. CTC provides new information with a
      different connectivity interpretation that can be used to analyse and design
      materials with complex microstructures.

PMID- 24671932
TI  - Alternative radical pairs for cryptochrome-based magnetoreception.
AB  - There is growing evidence that the remarkable ability of animals, in particular
      birds, to sense the direction of the Earth's magnetic field relies on
      magnetically sensitive photochemical reactions of the protein cryptochrome. It is
      generally assumed that the magnetic field acts on the radical pair [FAD*- TrpH*+]
      formed by the transfer of an electron from a group of three tryptophan residues
      to the photo-excited flavin adenine dinucleotide cofactor within the protein.
      Here, we examine the suitability of an [FAD*- Z*] radical pair as a compass
      magnetoreceptor, where Z* is a radical in which the electron spin has no
      hyperfine interactions with magnetic nuclei, such as hydrogen and nitrogen.
      Quantum spin dynamics simulations of the reactivity of [FAD*- Z*] show that it is
      two orders of magnitude more sensitive to the direction of the geomagnetic field
      than is [FAD*- TrpH*+] under the same conditions (50 uT magnetic field, 1 us
      radical lifetime). The favourable magnetic properties of [FAD*- Z*] arise from
      the asymmetric distribution of hyperfine interactions among the two radicals and
      the near-optimal magnetic properties of the flavin radical. We close by
      discussing the identity of Z* and possible routes for its formation as part of a
      spin-correlated radical pair with an FAD radical in cryptochrome.

PMID- 24671933
TI  - A theoretical study of biological membrane response to temperature gradients at
      the single-cell level.
AB  - Recent experimental studies provide evidence for the existence of a spatially non
      uniform temperature field in living cells and in particular in their plasma
      membrane. These findings have led to the development of a new and exciting field:
      thermal biology at the single-cell level. Here, we examine theoretically a
      specific aspect of this field, i.e. how temperature gradients at the single-cell
      level affect the phase behaviour and geometry of heterogeneous membranes. We
      address this issue by using the Onsager reciprocal relations combined with a
      simple model for a binary lipid mixture. We demonstrate that even small
      temperature variations along the membrane may introduce intriguing phenomena,
      such as phase separation above the critical temperature and unusual shape
      response. These results also suggest that the shape of a membrane can be
      manipulated by dynamically controlling the temperature field in its vicinity. The
      effects of intramembranous temperature gradients have never been studied
      experimentally. Thus, the predictions of the current contribution are of a
      somewhat speculative nature. Experimental verification of these results could
      mark the beginning of a new line of research in the field of biological
      membranes. We report our findings with the hope of inspiring others to perform
      such experiments. 

PMID- 24671934
TI  - Complex role of space in the crossing of fitness valleys by asexual populations.
AB  - The evolution of complex traits requires the accumulation of multiple mutations,
      which can be disadvantageous, neutral or advantageous relative to the wild-type.
      We study two spatial (two-dimensional) models of fitness valley crossing (the
      constant-population Moran process and the non-constant-population contact
      process), varying the number of loci involved and the degree of mixing. We find
      that spatial interactions accelerate the crossing of fitness valleys in the Moran
      process in the context of neutral and disadvantageous intermediate mutants
      because of the formation of mutant islands that increase the lifespan of mutant
      lineages. By contrast, in the contact process, spatial structure can accelerate
      or delay the emergence of the complex trait, and there can even be an optimal
      degree of mixing that maximizes the rate of evolution. For advantageous
      intermediate mutants, spatial interactions always delay the evolution of complex
      traits, in both the Moran and contact processes. The role of the mutant islands
      here is the opposite: instead of protecting, they constrict the growth of
      mutants. We conclude that the laws of population growth can be crucial for the
      effect of spatial interactions on the rate of evolution, and we relate the two
      processes explored here to different biological situations. 

PMID- 24671936
TI  - Single-site sonoporation disrupts actin cytoskeleton organization.
AB  - Sonoporation is based upon an ultrasound-microbubble cavitation routine that
      physically punctures the plasma membrane on a transient basis. During such a
      process, the actin cytoskeleton may be disrupted in tandem because this network
      of subcellular filaments is physically interconnected with the plasma membrane.
      Here, by performing confocal fluorescence imaging of single-site sonoporation
      episodes induced by ultrasound-triggered collapse of a single targeted
      microbubble, we directly observed immediate rupturing of filamentary actin (F
      actin) at the sonoporation site (cell type: ZR-75-30; ultrasound frequency: 1
      MHz; peak negative pressure: 0.45 MPa; pulse duration: 30 cycles; bubble
      diameter: 2-4 um). Also, through conducting a structure tensor analysis, we
      observed further disassembly of the F-actin network over the next 60 min after
      the onset of sonoporation. The extent of F-actin disruption was found to be more
      substantial in cells with higher uptake of sonoporation tracer. Commensurate with
      this process, cytoplasmic accumulation of globular actin (G-actin) was evident in
      sonoporated cells, and in turn the G-actin : F-actin ratio was increased in a
      trend similar to drug-induced (cytochalasin D) actin depolymerization. These
      results demonstrate that sonoporation is not solely a membrane-level phenomenon:
      organization of the actin cytoskeleton is concomitantly perturbed. 

PMID- 24671935
TI  - Pathophysiological mechanisms of high-intensity focused ultrasound-mediated
      vascular occlusion and relevance to non-invasive fetal surgery.
AB  - High-intensity focused ultrasound (HIFU) is a non-invasive technology, which can
      be used occlude blood vessels in the body. Both the theory underlying and
      practical process of blood vessel occlusion are still under development and
      relatively sparse in vivo experimental and therapeutic data exist. HIFU would
      however provide an alternative to surgery, particularly in circumstances where
      serious complications inherent to surgery outweigh the potential benefits.
      Accordingly, the HIFU technique would be of particular utility for fetal and
      placental interventions, where open or endoscopic surgery is fraught with
      difficulty and likelihood of complications including premature delivery. This
      assumes that HIFU could be shown to safely and effectively occlude blood vessels
      in utero. To understand these mechanisms more fully, we present a review of
      relevant cross-specialty literature on the topic of vascular HIFU and suggest an
      integrative mechanism taking into account clinical, physical and engineering
      considerations through which HIFU may produce vascular occlusion. This model may
      aid in the design of HIFU protocols to further develop this area, and might be
      adapted to provide a non-invasive therapy for conditions in fetal medicine where
      vascular occlusion is beneficial. 

PMID- 24671937
TI  - A dose and time response Markov model for the in-host dynamics of infection with
      intracellular bacteria following inhalation: with application to Francisella
      tularensis.
AB  - In a novel approach, the standard birth-death process is extended to incorporate
      a fundamental mechanism undergone by intracellular bacteria, phagocytosis. The
      model accounts for stochastic interaction between bacteria and cells of the
      immune system and heterogeneity in susceptibility to infection of individual
      hosts within a population. Model output is the dose-response relation and the
      dose-dependent distribution of time until response, where response is the onset
      of symptoms. The model is thereafter parametrized with respect to the highly
      virulent Schu S4 strain of Francisella tularensis, in the first such study to
      consider a biologically plausible mathematical model for early human infection
      with this bacterium. Results indicate a median infectious dose of about 23
      organisms, which is higher than previously thought, and an average incubation
      period of between 3 and 7 days depending on dose. The distribution of incubation
      periods is right-skewed up to about 100 organisms and symmetric for larger doses.
      Moreover, there are some interesting parallels to the hypotheses of some of the
      classical dose-response models, such as independent action (single-hit model) and
      individual effective dose (probit model). The findings of this study support
      experimental evidence and postulations from other investigations that response
      is, in fact, influenced by both in-host and between-host variability. 

PMID- 24671938
TI  - Hygroscopic swelling and shrinkage of latewood cell wall micropillars reveal
      ultrastructural anisotropy.
AB  - We document the hygroscopic swelling and shrinkage of the central and the
      thickest secondary cell wall layer of wood (named S2) in response to changes in
      environmental humidity using synchrotron radiation-based phase contrast X-ray
      tomographic nanoscopy. The S2 layer is a natural fibre-reinforced nano-composite
      polymer and is strongly reactive to water. Using focused ion beam, micropillars
      with a cross section of few micrometres are fabricated from the S2 layer of the
      latewood cell walls of Norway spruce softwood. The thin neighbouring cell wall
      layers are removed to prevent hindering or restraining of moisture-induced
      deformation during swelling or shrinkage. The proposed experiment intended to get
      further insights into the microscopic origin of the anisotropic hygro-expansion
      of wood. It is found that the swelling/shrinkage strains are highly anisotropic
      in the transverse plane of the cell wall, larger in the normal than in the
      direction parallel to the cell wall's thickness. This ultrastructural anisotropy
      may be due to the concentric lamellation of the cellulose microfibrils as the
      role of the cellulose microfibril angle in the transverse swelling anisotropy is
      negligible. The volumetric swelling of the cell wall material is found to be
      substantially larger than the one of wood tissues within the growth ring and wood
      samples made of several growth rings. The hierarchical configuration in wood
      optimally increases its dimensional stability in response to a humid environment
      with higher scales of complexity. 

PMID- 24671939
TI  - Herpes simplex virus-2 transmission probability estimates based on quantity of
      viral shedding.
AB  - Herpes simplex virus (HSV)-2 is periodically shed in the human genital tract,
      most often asymptomatically, and most sexual transmissions occur during
      asymptomatic shedding. It would be helpful to identify a genital viral load
      threshold necessary for transmission, as clinical interventions that maintain
      viral quantity below this level would be of high utility. However, because viral
      expansion, decay and re-expansion kinetics are extremely rapid during shedding
      episodes, it is impossible to directly measure genital viral load at the time of
      sexual activity. We developed a mathematical model based on reproducing shedding
      patterns in transmitting partners, and median number of sex acts prior to
      transmission in discordant couples, to estimate infectivity of single viral
      particles in the negative partner's genital tract. We then inferred probability
      estimates for transmission at different levels of genital tract viral load in the
      transmitting partner. We predict that transmission is unlikely at viral loads
      less than 10(4) HSV DNA copies. Moreover, most transmissions occur during
      prolonged episodes with high viral copy numbers. Many shedding episodes that
      result in transmission do not reach the threshold of clinical detection, because
      the ulcer remains very small, highlighting one reason why HSV-2 spreads so
      effectively within populations. 

PMID- 24671940
TI  - Ferrous iron formation following the co-aggregation of ferric iron and the
      Alzheimer's disease peptide beta-amyloid (1-42).
AB  - For decades, a link between increased levels of iron and areas of Alzheimer's
      disease (AD) pathology has been recognized, including AD lesions comprised of the
      peptide beta-amyloid (Abeta). Despite many observations of this association, the
      relationship between Abeta and iron is poorly understood. Using X-ray
      microspectroscopy, X-ray absorption spectroscopy, electron microscopy and
      spectrophotometric iron(II) quantification techniques, we examine the interaction
      between Abeta(1-42) and synthetic iron(III), reminiscent of ferric iron stores in
      the brain. We report Abeta to be capable of accumulating iron(III) within amyloid
      aggregates, with this process resulting in Abeta-mediated reduction of iron(III)
      to a redox-active iron(II) phase. Additionally, we show that the presence of
      aluminium increases the reductive capacity of Abeta, enabling the redox cycling
      of the iron. These results demonstrate the ability of Abeta to accumulate iron,
      offering an explanation for previously observed local increases in iron
      concentration associated with AD lesions. Furthermore, the ability of iron to
      form redox-active iron phases from ferric precursors provides an origin both for
      the redox-active iron previously witnessed in AD tissue, and the increased levels
      of oxidative stress characteristic of AD. These interactions between Abeta and
      iron deliver valuable insights into the process of AD progression, which may
      ultimately provide targets for disease therapies. 

PMID- 24671941
TI  - Understanding macroalgal dispersal in a complex hydrodynamic environment: a
      combined population genetic and physical modelling approach.
AB  - Gene flow in macroalgal populations can be strongly influenced by spore or gamete
      dispersal. This, in turn, is influenced by a convolution of the effects of
      current flow and specific plant reproductive strategies. Although several studies
      have demonstrated genetic variability in macroalgal populations over a wide range
      of spatial scales, the associated current data have generally been poorly
      resolved spatially and temporally. In this study, we used a combination of
      population genetic analyses and high-resolution hydrodynamic modelling to
      investigate potential connectivity between populations of the kelp Laminaria
      digitata in the Strangford Narrows, a narrow channel characterized by strong
      currents linking the large semi-enclosed sea lough, Strangford Lough, to the
      Irish Sea. Levels of genetic structuring based on six microsatellite markers were
      very low, indicating high levels of gene flow and a pattern of isolation-by
      distance, where populations are more likely to exchange migrants with
      geographically proximal populations, but with occasional long-distance dispersal.
      This was confirmed by the particle tracking model, which showed that, while the
      majority of spores settle near the release site, there is potential for dispersal
      over several kilometres. This combined population genetic and modelling approach
      suggests that the complex hydrodynamic environment at the entrance to Strangford
      Lough can facilitate dispersal on a scale exceeding that proposed for L. digitata
      in particular, and the majority of macroalgae in general. The study demonstrates
      the potential of integrated physical-biological approaches for the prediction of
      ecological changes resulting from factors such as anthropogenically induced
      coastal zone changes. 

PMID- 24671942
TI  - Intra-articular decorin influences the fibrosis genetic expression profile in a
      rabbit model of joint contracture.
AB  - OBJECTIVES: The goal of this study was to determine whether intra-articular
      administration of the potentially anti-fibrotic agent decorin influences the
      expression of genes involved in the fibrotic cascade, and ultimately leads to
      less contracture, in an animal model. METHODS: A total of 18 rabbits underwent an
      operation on their right knees to form contractures. Six limbs in group 1
      received four intra-articular injections of decorin; six limbs in group 2
      received four intra-articular injections of bovine serum albumin (BSA) over eight
      days; six limbs in group 3 received no injections. The contracted limbs of
      rabbits in group 1 were biomechanically and genetically compared with the
      contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint
      measuring device and custom microarray, respectively. RESULTS: There was no
      statistical difference in the flexion contracture angles between those limbs that
      received intra-articular decorin versus those that received intra-articular BSA
      (66 degrees  vs 69 degrees ; p = 0.41). Likewise, there was no statistical
      difference between those limbs that received intra-articular decorin versus those
      who had no injection (66 degrees  vs 72 degrees ; p = 0.27). When compared with
      BSA, decorin led to a statistically significant increase in the mRNA expression
      of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA
      expression of three genes, when compared with those without injection.
      CONCLUSIONS: In this model, when administered intra-articularly at eight weeks, 2
      mg of decorin had no significant effect on joint contractures. However, our
      genetic analysis revealed a significant alteration in several fibrotic genes.
      Cite this article: Bone Joint Res 2014;3:82-8.

PMID- 24671943
TI  - The relationship of sex hormone-binding globulin (SHBG) gene polymorphisms with
      serum SHBG level and metabolic syndrome in Chinese Han males.
AB  - OBJECTIVE: Epidemiological studies have shown that circulating sex hormone
      binding globulin (SHBG) levels are lower in metabolic syndrome (MetS) patients
      than in non-MetS individuals. In this study, we investigated the relationship of
      polymorphisms in the SHBG gene with the serum SHBG levels and MetS in Han
      Chinese. METHODS: We performed a cross-sectional study of 316 subjects who were
      recruited from a health checkup population at Zhongshan Hospital, Fudan
      University. Anthropometric measurements, blood pressure, fasting plasma glucose,
      lipid levels, total testosterone, and SHBG levels were obtained in addition to
      the seven SHBG single-nucleotide polymorphisms (SNPs). RESULTS: The variant
      allele (AG or AA) carriers in rs6259, compared to the wild-type allele carriers
      (GG), have a lower risk for MetS [OR 0.56, 95% confidence interval (CI) 0.33
      0.96] and higher serum SHBG and TT levels (P = 0.016, 0.004). CT or TT allele
      carriers in rs3760213, compared to CC allele carriers, also have a lower risk for
      MetS (OR 0.59, 95 % CI 0.34-1.00) and significantly higher SHBG and TT levels (P
      = 0.029, 0.009). Carriers having both of the variant alleles had the lowest risk
      of MetS (OR 0.51, 95 % CI 0.275-0.950) and the highest SHBG levels. The risk of
      MetS rose with the decrease in serum SHBG levels for rs6259 and rs376021
      carriers. CONCLUSION: rs6259 and rs3760213 SNPs are associated with the risk of
      MetS and lower serum SHBG level in Chinese Han males.

PMID- 24671945
TI  - Tight glycemic control after pediatric cardiac surgery in high-risk patient
      populations: a secondary analysis of the safe pediatric euglycemia after cardiac
      surgery trial.
AB  - BACKGROUND: Our previous randomized, clinical trial showed that postoperative
      tight glycemic control (TGC) for children undergoing cardiac surgery did not
      reduce the rate of health care-associated infections compared with standard care
      (STD). Heterogeneity of treatment effect may exist within this population.
      METHODS AND RESULTS: We performed a post hoc exploratory analysis of 980 children
      from birth to 36 months of age at the time of cardiac surgery who were randomized
      to postoperative TGC or STD in the intensive care unit. Significant interactions
      were observed between treatment group and both neonate (age <=30 days; P=0.03)
      and intraoperative glucocorticoid exposure (P=0.03) on the risk of infection. The
      rate and incidence of infections in subjects <=60 days old were significantly
      increased in the TGC compared with the STD group (rate: 13.5 versus 3.7
      infections per 1000 cardiac intensive care unit days, P=0.01; incidence: 13%
      versus 4%, P=0.02), whereas infections among those >60 days of age were
      significantly reduced in the TGC compared with the STD group (rate: 5.0 versus
      14.1 infections per 1000 cardiac intensive care unit days, P=0.02; incidence: 2%
      versus 5%, P=0.03); the interaction of treatment group by age subgroup was highly
      significant (P=0.001). Multivariable logistic regression controlling for the main
      effects revealed that previous cardiac surgery, chromosomal anomaly, and delayed
      sternal closure were independently associated with increased risk of infection.
      CONCLUSIONS: This exploratory analysis demonstrated that TGC may lower the risk
      of infection in children >60 days of age at the time of cardiac surgery compared
      with children receiving STD. Meta-analyses of past and ongoing clinical trials
      are necessary to confirm these findings before clinical practice is altered.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00443599.

PMID- 24671947
TI  - Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni.
AB  - Members of the genus Campylobacter are frequently responsible for human enteric
      disease, often through consumption of contaminated poultry products.
      Bacteriophages are viruses that have the potential to control pathogenic
      bacteria, but understanding their complex life cycles is key to their successful
      exploitation. Treatment of Campylobacter jejuni biofilms with bacteriophages led
      to the discovery that phages had established a relationship with their hosts
      typical of the carrier state life cycle (CSLC), where bacteria and bacteriophages
      remain associated in equilibrium. Significant phenotypic changes include improved
      aerotolerance under nutrient-limited conditions that would confer an advantage to
      survive in extra-intestinal environments, but a lack in motility eliminated their
      ability to colonize chickens. Under these circumstances, phages can remain
      associated with a compatible host and continue to produce free virions to
      prospect for new hosts. Moreover, we demonstrate that CSLC host bacteria can act
      as expendable vehicles for the delivery of bacteriophages to new host bacteria
      within pre-colonized chickens. The CSLC represents an important phase in the
      ecology of Campylobacter bacteriophage. 

PMID- 24671946
TI  - Molecular basis for the fold organization and sarcomeric targeting of the muscle
      atrogin MuRF1.
AB  - MuRF1 is an E3 ubiquitin ligase central to muscle catabolism. It belongs to the
      TRIM protein family characterized by a tripartite fold of RING, B-box and coiled
      coil (CC) motifs, followed by variable C-terminal domains. The CC motif is
      hypothesized to be responsible for domain organization in the fold as well as for
      high-order assembly into functional entities. But data on CC from this family
      that can clarify the structural significance of this motif are scarce. We have
      characterized the helical region from MuRF1 and show that, contrary to
      expectations, its CC domain assembles unproductively, being the B2- and COS-boxes
      in the fold (respectively flanking the CC) that promote a native quaternary
      structure. In particular, the C-terminal COS-box seemingly forms an alpha-hairpin
      that packs against the CC, influencing its dimerization. This shows that a C
      terminal variable domain can be tightly integrated within the conserved TRIM fold
      to modulate its structure and function. Furthermore, data from transfected muscle
      show that in MuRF1 the COS-box mediates the in vivo targeting of sarcoskeletal
      structures and points to the pharmacological relevance of the COS domain for
      treating MuRF1-mediated muscle atrophy. 

PMID- 24671948
TI  - Are we there yet? Initial targeting of the Male-Specific Lethal and Polycomb
      group chromatin complexes in Drosophila.
AB  - Chromatin-binding proteins must navigate the complex nuclear milieu to find their
      sites of action, and a constellation of protein factors and other properties are
      likely to influence targeting specificity. Despite considerable progress, the
      precise rules by which binding specificity is achieved have remained elusive.
      Here, we consider early targeting events for two groups of chromatin-binding
      complexes in Drosophila: the Male-Specific Lethal (MSL) and the Polycomb group
      (PcG) complexes. These two serve as models for understanding targeting, because
      they have been extensively studied and play vital roles in Drosophila, and their
      targets have been documented at high resolution. Furthermore, the proteins and
      biochemical properties of both complexes are largely conserved in multicellular
      organisms, including humans. While the MSL complex increases gene expression and
      PcG members repress genes, the two groups share many similarities such as the
      ability to modify their chromatin environment to create active or repressive
      domains, respectively. With legacies of in-depth genetic, biochemical and now
      genomic approaches, the MSL and PcG complexes will continue to provide tractable
      systems for understanding the recruitment of multiprotein chromatin complexes to
      their target loci. 

PMID- 24671951
TI  - High-throughput transcription profiling identifies putative epigenetic regulators
      of hematopoiesis.
AB  - Hematopoietic differentiation is governed by a complex regulatory program
      controlling the generation of different lineages of blood cells from multipotent
      hematopoietic stem cells. The transcriptional program that dictates hematopoietic
      cell fate and differentiation requires an epigenetic memory function provided by
      a network of epigenetic factors regulating DNA methylation, posttranslational
      histone modifications, and chromatin structure. Aberrant interactions between
      epigenetic factors and transcription factors cause perturbations in the blood
      cell differentiation program that result in various types of hematopoietic
      disorders. To elucidate the contributions of different epigenetic factors in
      human hematopoiesis, high-throughput cap analysis of gene expression was used to
      build transcription profiles of 199 epigenetic factors in a wide range of blood
      cells. Our epigenetic transcriptome analysis revealed cell type- (eg, HELLS and
      ACTL6A), lineage- (eg, MLL), and/or leukemia- (eg, CHD2, CBX8, and EPC1) specific
      expression of several epigenetic factors. In addition, we show that several
      epigenetic factors use alternative transcription start sites in different cell
      types. This analysis could serve as a resource for the scientific community for
      further characterization of the role of these epigenetic factors in blood
      development.

PMID- 24671950
TI  - A Caenorhabditis elegans developmental decision requires insulin signaling
      mediated neuron-intestine communication.
AB  - Adverse environmental conditions trigger C. elegans larvae to activate an
      alternative developmental program, termed dauer diapause, which renders them
      stress resistant. High-level insulin signaling prevents constitutive dauer
      formation. However, it is not fully understood how animals assess conditions to
      choose the optimal developmental program. Here, we show that insulin-like peptide
      (ILP)-mediated neuron-intestine communication plays a role in this developmental
      decision. Consistent with, and extending, previous findings, we show that the
      simultaneous removal of INS-4, INS-6 and DAF-28 leads to fully penetrant
      constitutive dauer formation, whereas the removal of INS-1 and INS-18
      significantly inhibits constitutive dauer formation. These ligands are processed
      by the proprotein convertases PC1/KPC-1 and/or PC2/EGL-3. The agonistic and
      antagonistic ligands are expressed by, and function in, neurons to prevent or
      promote dauer formation. By contrast, the insulin receptor DAF-2 and its
      effector, the FOXO transcription factor DAF-16, function solely in the intestine
      to regulate the decision to enter diapause. These results suggest that the
      nervous system normally establishes an agonistic ILP-dominant paradigm to inhibit
      intestinal DAF-16 activation and allow reproductive development. Under adverse
      conditions, a switch in the agonistic-antagonistic ILP balance activates
      intestinal DAF-16, which commits animals to diapause. 

PMID- 24671949
TI  - In vivo fluorescence lifetime imaging for monitoring the efficacy of the cancer
      treatment.
AB  - PURPOSE: Advances in tumor biology created a foundation for targeted therapy
      aimed at inactivation of specific molecular mechanisms responsible for cell
      malignancy. In this paper, we used in vivo fluorescence lifetime imaging with
      HER2-targeted fluorescent probes as an alternative imaging method to investigate
      the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with
      high expression of HER2 receptors. EXPERIMENTAL DESIGN: HER2-specific Affibody,
      conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive
      tumor xenograft. The fluorescence lifetime was measured before treatment and
      monitored after the probe injections at 12 hours after the last treatment dose,
      when the response to the 17-DMAG therapy was the most pronounced as well as a
      week after the last treatment when the tumors grew back almost to their
      pretreatment size. RESULTS: Imaging results showed significant difference between
      the fluorescence lifetimes at the tumor and the contralateral site (~0.13 ns) in
      the control group (before treatment) and 7 days after the last treatment when the
      tumors grew back to their pretreatment dimensions. However, at the time frame
      that the treatment had its maximum effect (12 hours after the last treatment),
      the difference between the fluorescence lifetime at the tumor and contralateral
      site decreased to 0.03 ns. CONCLUSIONS: The results showed a good correlation
      between fluorescence lifetime and the efficacy of the treatment. These findings
      show that in vivo fluorescence lifetime imaging can be used as a promising
      molecular imaging tool for monitoring the treatment outcome in preclinical models
      and potentially in patients.

PMID- 24671952
TI  - Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed
      changes and dynamic enhancer methylation.
AB  - In development, epigenetic mechanisms such as DNA methylation have been suggested
      to provide a cellular memory to maintain multipotency but also stabilize cell
      fate decisions and direct lineage restriction. In this study, we set out to
      characterize changes in DNA methylation and gene expression during granulopoiesis
      using 4 distinct cell populations ranging from the oligopotent common myeloid
      progenitor stage to terminally differentiated neutrophils. We observed that
      differentially methylated sites (DMSs) generally show decreased methylation
      during granulopoiesis. Methylation appears to change at specific differentiation
      stages and overlap with changes in transcription and activity of key
      hematopoietic transcription factors. DMSs were preferentially located in areas
      distal to CpG islands and shores. Also, DMSs were overrepresented in enhancer
      elements and enriched in enhancers that become active during differentiation.
      Overall, this study depicts in detail the epigenetic and transcriptional changes
      that occur during granulopoiesis and supports the role of DNA methylation as a
      regulatory mechanism in blood cell differentiation.

PMID- 24671953
TI  - The enhancer and promoter landscape of human regulatory and conventional T-cell
      subpopulations.
AB  - CD4(+)CD25(+)FOXP3(+) human regulatory T cells (Tregs) are essential for self
      tolerance and immune homeostasis. Here, we describe the promoterome of
      CD4(+)CD25(high)CD45RA(+) naive and CD4(+)CD25(high)CD45RA(-) memory Tregs and
      their CD25(-) conventional T-cell (Tconv) counterparts both before and after in
      vitro expansion by cap analysis of gene expression (CAGE) adapted to single
      molecule sequencing (HeliScopeCAGE). We performed comprehensive comparative
      digital gene expression analyses and revealed novel transcription start sites, of
      which several were validated as alternative promoters of known genes. For all in
      vitro expanded subsets, we additionally generated global maps of poised and
      active enhancer elements marked by histone H3 lysine 4 monomethylation and
      histone H3 lysine 27 acetylation, describe their cell type-specific motif
      signatures, and evaluate the role of candidate transcription factors STAT5,
      FOXP3, RUNX1, and ETS1 in both Treg- and Tconv-specific enhancer architectures.
      Network analyses of gene expression data revealed additional candidate
      transcription factors contributing to cell type specificity and a transcription
      factor network in Tregs that is dominated by FOXP3 interaction partners and
      targets. In summary, we provide a comprehensive and easily accessible resource of
      gene expression and gene regulation in human Treg and Tconv subpopulations.

PMID- 24671955
TI  - Transcription and enhancer profiling in human monocyte subsets.
AB  - Human blood monocytes comprise at least 3 subpopulations that differ in phenotype
      and function. Here, we present the first in-depth regulome analysis of human
      classical (CD14(++)CD16(-)), intermediate (CD14(+)CD16(+)), and nonclassical
      (CD14(dim)CD16(+)) monocytes. Cap analysis of gene expression adapted to Helicos
      single-molecule sequencing was used to map transcription start sites throughout
      the genome in all 3 subsets. In addition, global maps of H3K4me1 and H3K27ac
      deposition were generated for classical and nonclassical monocytes defining
      enhanceosomes of the 2 major subsets. We identified differential regulatory
      elements (including promoters and putative enhancers) that were associated with
      subset-specific motif signatures corresponding to different transcription factor
      activities and exemplarily validated novel downstream enhancer elements at the
      CD14 locus. In addition to known subset-specific features, pathway analysis
      revealed marked differences in metabolic gene signatures. Whereas classical
      monocytes expressed higher levels of genes involved in carbohydrate metabolism,
      priming them for anaerobic energy production, nonclassical monocytes expressed
      higher levels of oxidative pathway components and showed a higher mitochondrial
      routine activity. Our findings describe promoter/enhancer landscapes and provide
      novel insights into the specific biology of human monocyte subsets.

PMID- 24671956
TI  - New analysis fuels debate on merits of prescribing statins to low risk people.

PMID- 24671954
TI  - Redefinition of the human mast cell transcriptome by deep-CAGE sequencing.
AB  - Mast cells (MCs) mature exclusively in peripheral tissues, hampering research
      into their developmental and functional programs. Here, we employed deep cap
      analysis of gene expression on skin-derived MCs to generate the most
      comprehensive view of the human MC transcriptome ever reported. An advantage is
      that MCs were embedded in the FANTOM5 project, giving the opportunity to contrast
      their molecular signature against a multitude of human samples. We demonstrate
      that MCs possess a unique and surprising transcriptional landscape, combining
      hematopoietic genes with those exclusively active in MCs and genes not previously
      reported as expressed by MCs (several of them markers of unrelated tissues). We
      also found functional bone morphogenetic protein receptors transducing activatory
      signals in MCs. Conversely, several immune-related genes frequently studied in
      MCs were not expressed or were weakly expressed. Comparing MCs ex vivo with
      cultured counterparts revealed profound changes in the MC transcriptome in in
      vitro surroundings. We also determined the promoter usage of MC-expressed genes
      and identified associated motifs active in the lineage. Befitting their
      uniqueness, MCs had no close relative in the hematopoietic network (also only
      distantly related with basophils). This rich data set reveals that our knowledge
      of human MCs is still limited, but with this resource, novel functional programs
      of MCs may soon be discovered.

PMID- 24671957
TI  - Differential effects of Rifampin and Ketoconazole on the blood and liver
      concentration of atorvastatin in wild-type and Cyp3a and Oatp1a/b knockout mice.
AB  - Atorvastatin is eliminated by CYP3A4 which follows carrier-mediated uptake into
      hepatocytes by OATP1B1, OATP1B3, and OATP2B1. Multiple clinical studies
      demonstrated that OATP inhibition by rifampin had a greater impact on
      atorvastatin systemic concentration than itraconazole-mediated CYP3A4 inhibition.
      If it is assumed that the blood and hepatocyte compartments are differentiated by
      the concentration gradient that is established by OATPs, and if the rate of
      uptake into the hepatocyte is rate-determining to the elimination of atorvastatin
      from the body, then it is hypothesized that blood concentrations may not
      necessarily reflect liver concentrations. In wild-type mice, rifampin had a
      greater effect on systemic exposure of atorvastatin than ketoconazole, as the
      blood area under the blood concentration-time curve increased 7- and 2-fold,
      respectively. In contrast, liver concentrations were affected more by
      ketoconazole than by rifampin, as liver levels increased 21- and 4-fold,
      respectively. Similarly, in Cyp3a knockout animals, 39-fold increases in liver
      concentrations were observed despite insignificant changes in the blood area
      under the blood concentration-time curve. Interestingly, blood and liver levels
      in Oatp1a/b knockout animals were similar to wild types, suggesting that Oatp1a/b
      knockout may be necessary but not sufficient to completely describe atorvastatin
      uptake in mice. Data presented in this work indicate that there is a substantial
      drug interaction when blocking atorvastatin metabolism, but the effects of this
      interaction are predominantly manifested in the liver and may not be captured
      when monitoring changes in the systemic circulation. Consequently, there may be a
      disconnect when trying to relate blood exposure to instances of hepatotoxicity
      because a pharmacokinetic-toxicity relationship may not be obvious from blood
      concentrations. 

PMID- 24671958
TI  - Deletion of 30 murine cytochrome p450 genes results in viable mice with
      compromised drug metabolism.
AB  - In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent
      monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene
      clusters account for ~80% of this activity. There are profound species
      differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse
      models to predict pathways of drug metabolism is further complicated by
      overlapping substrate specificity between enzymes from different gene families.
      To establish the role of the hepatic and extrahepatic P450 system in drug and
      foreign chemical disposition, drug efficacy, and toxicity, we created a unique
      mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a
      gene clusters have been deleted. Remarkably, despite a wide range of putative
      important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile,
      demonstrating that these genes have evolved primarily as detoxification enzymes.
      Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO
      mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic
      morphology and a decreased blood glucose (30%) were also noted. A five-drug
      cocktail of cytochrome P450 isozyme probe substrates were used to evaluate
      changes in drug pharmacokinetics; marked changes were observed in either the
      pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates,
      whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus,
      Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the
      P450 system in drug metabolism and efficacy, as well as in chemical toxicity. 

PMID- 24671959
TI  - NICE tells local planners to improve access to contraception services.

PMID- 24671960
TI  - Drinking problems on a 'simple' diet: physiological convergence in nectar-feeding
      birds.
AB  - Regulation of energy and water are by necessity closely linked in avian
      nectarivores, because the easily available sugars in nectar are accompanied by an
      excess of water but few electrolytes. In general, there is convergence in
      morphology and physiology between three main lineages of avian nectarivores that
      have evolved on different continents - the hummingbirds, sunbirds and
      honeyeaters. These birds show similar dependence of sugar preferences on nectar
      concentration, high intestinal sucrase activity and rapid absorption of hexoses
      via mediated and paracellular routes. There are differences, however, in how
      these lineages deal with energy challenges, as well as processing the large
      volumes of preformed water ingested in nectar. While hummingbirds rely on varying
      renal water reabsorption, the passerine nectarivores modulate intestinal water
      absorption during water loading, thus reducing the impact on the kidneys.
      Hummingbirds do not generally cope with salt loading, and have renal morphology
      consistent with their ability to produce copious dilute urine; by contrast, as
      well as being able to deal with dilute diets, honeyeaters and sunbirds are more
      than capable of dealing with moderately high levels of added electrolytes. And
      finally, in response to energy challenge, hummingbirds readily resort to torpor,
      while the passerines show renal and digestive responses that allow them to deal
      with short-term fasts and rapidly restore energy balance without using torpor. In
      conclusion, sunbirds and honeyeaters demonstrate a degree of physiological
      plasticity in dealing with digestive and renal challenges of their nectar diet,
      while hummingbirds appear to be more constrained by this diet. 

PMID- 24671962
TI  - Biomechanical determinants of bite force dimorphism in Cyclommatus metallifer
      stag beetles.
AB  - In the stag beetle family (Lucanidae), males have diverged from females by sexual
      selection. The males fight each other for mating opportunities with their
      enlarged mandibles. It is known that owners of larger fighting apparatuses are
      favoured to win the male-male fights, but it was unclear whether male stag
      beetles also need to produce high bite forces while grabbing and lifting
      opponents in fights. We show that male Cyclommatus metallifer stag beetles bite
      three times as forcefully as females. This is not entirely unexpected given the
      spectacular nature of the fights, but all the more impressive given the
      difficulty of achieving this with their long mandibles (long levers). Our results
      suggest no increase in male intrinsic muscle strength to accomplish this.
      However, morphological analyses show that the long mandibular output levers in
      males are compensated by elongated input levers (and thus a wider anterior side
      of the head). The surplus of male bite force capability is realized by
      enlargement of the closer muscles of the mandibles, while overall muscle force
      direction remained optimal. To enable the forceful bites required to ensure male
      reproductive success, male head size and shape are adapted for long input levers
      and large muscles. Therefore, the entire head should be regarded as an integral
      part of male armature. 

PMID- 24671961
TI  - No oxygen? No problem! Intrinsic brain tolerance to hypoxia in vertebrates.
AB  - Many vertebrates are challenged by either chronic or acute episodes of low oxygen
      availability in their natural environments. Brain function is especially
      vulnerable to the effects of hypoxia and can be irreversibly impaired by even
      brief periods of low oxygen supply. This review describes recent research on
      physiological mechanisms that have evolved in certain vertebrate species to cope
      with brain hypoxia. Four model systems are considered: freshwater turtles that
      can survive for months trapped in frozen-over lakes, arctic ground squirrels that
      respire at extremely low rates during winter hibernation, seals and whales that
      undertake breath-hold dives lasting minutes to hours, and naked mole-rats that
      live in crowded burrows completely underground for their entire lives. These
      species exhibit remarkable specializations of brain physiology that adapt them
      for acute or chronic episodes of hypoxia. These specializations may be reactive
      in nature, involving modifications to the catastrophic sequelae of oxygen
      deprivation that occur in non-tolerant species, or preparatory in nature,
      preventing the activation of those sequelae altogether. Better understanding of
      the mechanisms used by these hypoxia-tolerant vertebrates will increase
      appreciation of how nervous systems are adapted for life in specific ecological
      niches as well as inform advances in therapy for neurological conditions such as
      stroke and epilepsy. 

PMID- 24671964
TI  - Master of all trades: thermal acclimation and adaptation of cardiac function in a
      broadly distributed marine invasive species, the European green crab, Carcinus
      maenas.
AB  - As global warming accelerates, there is increasing concern about how ecosystems
      may change as a result of species loss and replacement. Here, we examined the
      thermal physiology of the European green crab (Carcinus maenas Linnaeus 1758), a
      globally invasive species, along three parallel thermal gradients in its native
      and invasive ranges. At each site, we assessed cardiac physiology to determine
      heat and cold tolerance and acclimatory plasticity. We found that, overall, the
      species is highly tolerant of both heat and cold, and that it survives higher
      temperatures than co-occurring native marine crustaceans. Further, we found that
      both heat and cold tolerance are plastic in response to short-term acclimation
      (18-31 days at either 5 or 25 degrees C). Comparing patterns within ranges, we
      found latitudinal gradients in thermal tolerance in the native European range and
      in the invasive range in eastern North America. This pattern is strongest in the
      native range, and likely evolved there. Because of a complicated invasion
      history, the latitudinal pattern in the eastern North American invasive range may
      be due either to rapid adaptation post-invasion or to adaptive differences
      between the ancestral populations that founded the invasion. Overall, the broad
      thermal tolerance ranges of green crabs, which may facilitate invasion of novel
      habitats, derive from high inherent eurythermality and acclimatory plasticity and
      potentially adaptive differentiation among populations. The highly flexible
      physiology that results from these capacities may represent the hallmark of a
      successful invasive species, and may provide a model for success in a changing
      world. 

PMID- 24671963
TI  - Biophysics of directional hearing in the American alligator (Alligator
      mississippiensis).
AB  - Physiological and anatomical studies have suggested that alligators have unique
      adaptations for spatial hearing. Sound localization cues are primarily generated
      by the filtering of sound waves by the head. Different vertebrate lineages have
      evolved external and/or internal anatomical adaptations to enhance these cues,
      such as pinnae and interaural canals. It has been hypothesized that in
      alligators, directionality may be enhanced via the acoustic coupling of middle
      ear cavities, resulting in a pressure difference receiver (PDR) mechanism. The
      experiments reported here support a role for a PDR mechanism in alligator sound
      localization by demonstrating that (1) acoustic space cues generated by the
      external morphology of the animal are not sufficient to generate location cues
      that match physiological sensitivity, (2) continuous pathways between the middle
      ears are present to provide an anatomical basis for coupling, (3) the auditory
      brainstem response shows some directionality, and (4) eardrum movement is
      directionally sensitive. Together, these data support the role of a PDR mechanism
      in crocodilians and further suggest this mechanism is a shared archosaur trait,
      most likely found also in the extinct dinosaurs. 

PMID- 24671965
TI  - Common effect of the mucus transferred during mating in two dart-shooting snail
      species from different families.
AB  - Several taxa of pulmonate land snails exhibit a conspicuous mating behaviour, the
      shooting of so-called love darts. During mating, such land snail species stab a
      mating partner with a mucus-coated dart. It has previously been shown that the
      sperm donor physiologically influences the sperm recipient via the mucus covering
      the dart and thereby decreases the number of sperm digested by the recipient.
      However, the generality of this effect of the dart's mucus is unclear, because
      almost all the previous studies on the effect of the mucus used the brown garden
      snail Cornu aspersum from the family Helicidae. Therefore, the relationship
      between the acquisition of the mucus effect on the recipient and the evolution of
      the dart itself, and its mucus, is still open to debate. To test the commonality
      of the physiological effect of the dart mucus, we examined this in Euhadra
      peliomphala, a species from the Bradybaenidae family, and compared our findings
      with the results of previous work using C. aspersum. Our experiments showed that
      in E. peliomphala, the dart mucus had a physiological effect and lowered the
      accessibility of the gametolytic organ, as found in C. aspersum. This indicates
      that in various dart-bearing species the mucus from the dart glands targets the
      same organ and that the inhibition of sperm digestion has played a crucial role
      in the evolution of the dart and its mucus. 

PMID- 24671966
TI  - Collecting data on patient experience is not enough: they must be used to improve
      care.

PMID- 24671967
TI  - Raiding the public health budget.

PMID- 24671968
TI  - Occam's Razor in sensorimotor learning.
AB  - A large number of recent studies suggest that the sensorimotor system uses
      probabilistic models to predict its environment and makes inferences about
      unobserved variables in line with Bayesian statistics. One of the important
      features of Bayesian statistics is Occam's Razor--an inbuilt preference for
      simpler models when comparing competing models that explain some observed data
      equally well. Here, we test directly for Occam's Razor in sensorimotor control.
      We designed a sensorimotor task in which participants had to draw lines through
      clouds of noisy samples of an unobserved curve generated by one of two possible
      probabilistic models-a simple model with a large length scale, leading to smooth
      curves, and a complex model with a short length scale, leading to more wiggly
      curves. In training trials, participants were informed about the model that
      generated the stimulus so that they could learn the statistics of each model. In
      probe trials, participants were then exposed to ambiguous stimuli. In probe
      trials where the ambiguous stimulus could be fitted equally well by both models,
      we found that participants showed a clear preference for the simpler model.
      Moreover, we found that participants' choice behaviour was quantitatively
      consistent with Bayesian Occam's Razor. We also show that participants' drawn
      trajectories were similar to samples from the Bayesian predictive distribution
      over trajectories and significantly different from two non-probabilistic
      heuristics. In two control experiments, we show that the preference of the
      simpler model cannot be simply explained by a difference in physical effort or by
      a preference for curve smoothness. Our results suggest that Occam's Razor is a
      general behavioural principle already present during sensorimotor processing.

PMID- 24671969
TI  - A critique of Rossberg et al.: Noise obscures the genetic signal of meiobiotal
      ecospecies in ecogenomic datasets.

PMID- 24671970
TI  - Metabolic dominance of bivalves predates brachiopod diversity decline by more
      than 150 million years.
AB  - Brachiopods and bivalves feed in similar ways and have occupied the same
      environments through geological time, but brachiopods were far more diverse and
      abundant in the Palaeozoic whereas bivalves dominate the post-Palaeozoic,
      suggesting a transition in ecological dominance 250 Ma. However, diversity and
      abundance data alone may not adequately describe key changes in ecosystem
      function, such as metabolic activity. Here, we use newly compiled body size data
      for 6066 genera of bivalves and brachiopods to calculate metabolic rates and
      revisit this question from the perspective of energy use, finding that bivalves
      already accounted for a larger share of metabolic activity in Palaeozoic oceans.
      We also find that the metabolic activity of bivalves has increased by more than
      two orders of magnitude over this interval, whereas brachiopod metabolic activity
      has declined by more than 50%. Consequently, the increase in bivalve energy
      metabolism must have occurred via the acquisition of new food resources rather
      than through the displacement of brachiopods. The canonical view of a mid
      Phanerozoic transition from brachiopod to bivalve dominance results from a focus
      on taxonomic diversity and numerical abundance as measures of ecological
      importance. From a metabolic perspective, the oceans have always belonged to the
      clams. 

PMID- 24671971
TI  - Personality drives physiological adjustments and is not related to survival.
AB  - The evolutionary function and maintenance of variation in animal personality is
      still under debate. Variation in the size of metabolic organs has recently been
      suggested to cause and maintain variation in personality. Here, we examine two
      main underlying notions: (i) that organ sizes vary consistently between
      individuals and cause consistent behavioural patterns, and (ii) that a more
      exploratory personality is associated with reduced survival. Exploratory
      behaviour of captive red knots (Calidris canutus, a migrant shorebird) was
      negatively rather than positively correlated with digestive organ (gizzard) mass,
      as well as with body mass. In an experiment, we reciprocally reduced and
      increased individual gizzard masses and found that exploration scores were
      unaffected. Whether or not these birds were resighted locally over the 19 months
      after release was negatively correlated with their exploration scores. Moreover,
      a long-term mark-recapture effort on free-living red knots with known gizzard
      masses at capture confirmed that local resighting probability (an inverse measure
      of exploratory behaviour) was correlated with gizzard mass without detrimental
      effects on survival. We conclude that personality drives physiological
      adjustments, rather than the other way around, and suggest that physiological
      adjustments mitigate the survival costs of exploratory behaviour. Our results
      show that we need to reconsider hypotheses explaining personality variation based
      on organ sizes and differential survival. 

PMID- 24671972
TI  - Evidence of social niche construction: persistent and repeated social
      interactions generate stronger personalities in a social spider.
AB  - While there are now a number of theoretical models predicting how consistent
      individual differences in behaviour may be generated and maintained, so far,
      there are few empirical tests. The social niche specialization hypothesis
      predicts that repeated social interactions among individuals may generate among
      individual differences and reinforce within-individual consistency through
      positive feedback mechanisms. Here, we test this hypothesis using groups of the
      social spider Stegodyphus mimosarum that differ in their level of familiarity. In
      support of the social niche specialization hypothesis, individuals in groups of
      spiders that were more familiar with each other showed greater repeatable among
      individual variation in behaviour. Additionally, individuals that were more
      familiar with each other exhibited lower within-individual variation in
      behaviour, providing one of the first examples of how the social environment can
      influence behavioural consistency. Our study demonstrates the potential for the
      social environment to generate and reinforce consistent individual differences in
      behaviour and provides a potentially general mechanism to explain this type of
      behavioural variation in animals with stable social groups. 

PMID- 24671973
TI  - Environmental heterogeneity affects the location of modelled communities along
      the niche-neutrality continuum.
AB  - The continuum hypothesis has been proposed as a means to reconcile the
      contradiction between the niche and neutral theories. While past research has
      shown that species richness affects the location of communities along the niche
      neutrality continuum, there may be extrinsic forces at play as well. We used a
      spatially explicit continuum model to quantify the effects of environmental
      heterogeneity, comprising abundance distribution and spatial configuration of
      resources, on the degree of community neutrality. We found that both components
      of heterogeneity affect the degree of community neutrality and that species'
      dispersal characteristics affect the neutrality-heterogeneity relationship.
      Narrower resource abundance distributions decrease neutrality, while spatial
      configuration, which is manifested by spatial aggregation of resources, decreases
      neutrality at higher aggregation levels. In general, the degree of community
      neutrality was affected by complex interactions among spatial configuration of
      resources, their abundance distributions and the dispersal characteristics of
      species in the community. Our results highlight the important yet overlooked role
      of the environment in dictating the location of communities along the
      hypothesized niche-neutrality continuum. 

PMID- 24671974
TI  - The dynamics of recovery and growth: how defoliation affects stored resources.
AB  - Growth rate varies widely among species and the trade-off between growth rate and
      storage or maintenance traits is a principal axis of variation between species.
      Many plant species have substantial root stores, but very little is known about
      how growth rate modifies responses of these stores to defoliation and other
      stresses. Species with different growth rates are predicted to respond in
      distinct ways, because of variation in the pre-defoliation allocation to storage.
      Here, we quantified the dynamics of stored carbohydrates in seven species with
      varying growth rate, following defoliation in a pot experiment. For faster
      growing species, there was significant reduction in carbohydrate concentration
      following defoliation, followed by relatively fast recovery, whereas for slower
      growing species, carbohydrate concentration levels remained relatively invariant
      across treatments. Results for total carbohydrates mirrored those for
      concentration, but were not as significant. Our findings were consistent with the
      idea that faster growing species respond more rapidly than slower growers to
      defoliation, through changes in carbohydrate pool concentrations. Growth rate as
      an indicator of life-history and ecological strategy may therefore be key to
      understanding post-defoliation recovery and storage strategies. 

PMID- 24671975
TI  - Sexual selection on protamine and transition nuclear protein expression in mouse
      species.
AB  - Post-copulatory sexual selection in the form of sperm competition is known to
      influence the evolution of male reproductive proteins in mammals. The
      relationship between sperm competition and regulatory evolution, however, remains
      to be explored. Protamines and transition nuclear proteins are involved in the
      condensation of sperm chromatin and are expected to affect the shape of the sperm
      head. A hydrodynamically efficient head allows for fast swimming velocity and,
      therefore, more competitive sperm. Previous comparative studies in rodents have
      documented a significant association between the level of sperm competition (as
      measured by relative testes mass) and DNA sequence evolution in both the coding
      and promoter sequences of protamine 2. Here, we investigate the influence of
      sexual selection on protamine and transition nuclear protein mRNA expression in
      the testes of eight mouse species that differ widely in levels of sperm
      competition. We also examined the relationship between relative gene expression
      levels and sperm head shape, assessed using geometric morphometrics. We found
      that species with higher levels of sperm competition express less protamine 2 in
      relation to protamine 1 and transition nuclear proteins. Moreover, there was a
      significant association between relative protamine 2 expression and sperm head
      shape. Reduction in the relative abundance of protamine 2 may increase the
      competitive ability of sperm in mice, possibly by affecting sperm head shape.
      Changes in gene regulatory sequences thus seem to be the basis of the
      evolutionary response to sexual selection in these proteins. 

PMID- 24671976
TI  - Rapid parallel evolution of standing variation in a single, complex, genomic
      region is associated with life history in steelhead/rainbow trout.
AB  - Rapid adaptation to novel environments may drive changes in genomic regions
      through natural selection. Such changes may be population-specific or,
      alternatively, may involve parallel evolution of the same genomic region in
      multiple populations, if that region contains genes or co-adapted gene complexes
      affecting the selected trait(s). Both quantitative and population genetic
      approaches have identified associations between specific genomic regions and the
      anadromous (steelhead) and resident (rainbow trout) life-history strategies of
      Oncorhynchus mykiss. Here, we use genotype data from 95 single nucleotide
      polymorphisms and show that the distribution of variation in a large region of
      one chromosome, Omy5, is strongly associated with life-history differentiation in
      multiple above-barrier populations of rainbow trout and their anadromous
      steelhead ancestors. The associated loci are in strong linkage disequilibrium,
      suggesting the presence of a chromosomal inversion or other rearrangement
      limiting recombination. These results provide the first evidence of a common
      genomic basis for life-history variation in O. mykiss in a geographically diverse
      set of populations and extend our knowledge of the heritable basis of rapid
      adaptation of complex traits in novel habitats. 

PMID- 24671977
TI  - Odours stimulate neuronal activity in the dorsolateral area of the hippocampal
      formation during path integration.
AB  - The dorsolateral area of the hippocampal formation of birds is commonly assumed
      to play a central role in processing information needed for geographical
      positioning and homing. Previous work has interpreted odour-induced activity in
      this region as evidence for an 'olfactory map'. Here, we show, using c-Fos
      expression as a marker, that neuronal activation in the dorsolateral area of the
      hippocampal formation of pigeons is primarily a response to odour novelty, not to
      the spatial distribution of odour sources that would be necessary for an
      olfactory map. Pigeons exposed to odours had significantly more neurons activated
      in this area of the brain than pigeons exposed to filtered air with odours
      removed. This increased activity was observed only in response to unfamiliar
      odours. No change in activity was observed when pigeons were exposed to home
      odours. These findings are consistent with non-home odours activating non
      olfactory components of the pigeon's navigation system. The pattern of neuronal
      activation in the triangular and dorsomedial areas of the hippocampal formation
      was, by contrast, consistent with the possibility that odours play a role in
      providing spatial information. 

PMID- 24671978
TI  - Into turbulent air: size-dependent effects of von Karman vortex streets on
      hummingbird flight kinematics and energetics.
AB  - Animal fliers frequently move through a variety of perturbed flows during their
      daily aerial routines. However, the extent to which these perturbations influence
      flight control and energetic expenditure is essentially unknown. Here, we
      evaluate the kinematic and metabolic consequences of flight within variably sized
      vortex shedding flows using five Anna's hummingbirds feeding from an artificial
      flower in steady control flow and within vortex wakes produced behind vertical
      cylinders. Tests were conducted at three horizontal airspeeds (3, 6 and 9 m s(
      1)) and using three different wake-generating cylinders (with diameters equal to
      38, 77 and 173% of birds' wing length). Only minimal effects on wing and body
      kinematics were demonstrated for flight behind the smallest cylinder, whereas
      flight behind the medium-sized cylinder resulted in significant increases in the
      variances of wingbeat frequency, and variances of body orientation, especially at
      higher airspeeds. Metabolic rate was, however, unchanged relative to that of
      unperturbed flight. Hummingbirds flying within the vortex street behind the
      largest cylinder exhibited highest increases in variances of wingbeat frequency,
      and of body roll, pitch and yaw amplitudes at all measured airspeeds.
      Impressively, metabolic rate under this last condition increased by up to 25%
      compared with control flights. Cylinder wakes sufficiently large to interact with
      both wings can thus strongly affect stability in flight, eliciting compensatory
      kinematic changes with a consequent increase in flight metabolic costs. Our
      findings suggest that vortical flows frequently encountered by aerial taxa in
      diverse environments may impose substantial energetic costs. 

PMID- 24671979
TI  - Current noise-removal methods can create false signals in ecogenomic data.

PMID- 24671980
TI  - Muir Gray: Evangelist for walking.

PMID- 24671982
TI  - The end of life.

PMID- 24671981
TI  - Derivation and validation of a clinical prediction rule for uncomplicated
      ureteral stone--the STONE score: retrospective and prospective observational
      cohort studies.
AB  - OBJECTIVE: To derive and validate an objective clinical prediction rule for the
      presence of uncomplicated ureteral stones in patients eligible for computed
      tomography (CT). We hypothesized that patients with a high probability of
      ureteral stones would have a low probability of acutely important alternative
      findings. DESIGN: Retrospective observational derivation cohort; prospective
      observational validation cohort. SETTING: Urban tertiary care emergency
      department and suburban freestanding community emergency department.
      PARTICIPANTS: Adults undergoing non-contrast CT for suspected uncomplicated
      kidney stone. The derivation cohort comprised a random selection of patients
      undergoing CT between April 2005 and November 2010 (1040 patients); the
      validation cohort included consecutive prospectively enrolled patients from May
      2011 to January 2013 (491 patients). MAIN OUTCOME MEASURES: In the derivation
      phase a priori factors potentially related to symptomatic ureteral stone were
      derived from the medical record blinded to the dictated CT report, which was
      separately categorized by diagnosis. Multivariate logistic regression was used to
      determine the top five factors associated with ureteral stone and these were
      assigned integer points to create a scoring system that was stratified into low,
      moderate, and high probability of ureteral stone. In the prospective phase this
      score was observationally derived blinded to CT results and compared with the
      prevalence of ureteral stone and important alternative causes of symptoms.
      RESULTS: The derivation sample included 1040 records, with five factors found to
      be most predictive of ureteral stone: male sex, short duration of pain, non-black
      race, presence of nausea or vomiting, and microscopic hematuria, yielding a score
      of 0-13 (the STONE score). Prospective validation was performed on 491
      participants. In the derivation and validation cohorts ureteral stone was present
      in, respectively, 8.3% and 9.2% of the low probability (score 0-5) group, 51.6%
      and 51.3% of the moderate probability (score 6-9) group, and 89.6% and 88.6% of
      the high probability (score 10-13) group. In the high score group, acutely
      important alternative findings were present in 0.3% of the derivation cohort and
      1.6% of the validation cohort. CONCLUSIONS: The STONE score reliably predicts the
      presence of uncomplicated ureteral stone and lower likelihood of acutely
      important alternative findings. Incorporation in future investigations may help
      to limit exposure to radiation and over-utilization of imaging. TRIAL
      REGISTRATION: www.clinicaltrials.gov NCT01352676.

PMID- 24671983
TI  - Sugary drinks in schools increase the risk of obesity in adolescents, study
      finds.

PMID- 24671984
TI  - So long for now.

PMID- 24671985
TI  - Climate change and human survival.

PMID- 24671986
TI  - UK research bodies agree steps to protect anonymity of study participants.

PMID- 24671987
TI  - Surgeon facing fitness to practise allegations can leave medical register.

PMID- 24671988
TI  - People in coastal regions of Asia are likely to be worst hit by climate change,
      report says.

PMID- 24671989
TI  - Trade talks between US and EU could increase cost of drugs, new report says.

PMID- 24671990
TI  - Targeting axonal regeneration: the growth cone takes the lead.

PMID- 24671991
TI  - Transient receptor potential channel ankyrin-1 is not a cold sensor for autonomic
      thermoregulation in rodents.
AB  - The rodent transient receptor potential ankyrin-1 (TRPA1) channel has been
      hypothesized to serve as a temperature sensor for thermoregulation in the cold.
      We tested this hypothesis by using deletion of the Trpa1 gene in mice and
      pharmacological blockade of the TRPA1 channel in rats. In both Trpa1(-/-) and
      Trpa1(+/+) mice, severe cold exposure (8 degrees C) resulted in decreases of skin
      and deep body temperatures to ~8 degrees C and 13 degrees C, respectively, both
      temperatures being below the reported 17 degrees C threshold temperature for
      TRPA1 activation. Under these conditions, Trpa1(-/-) mice had the same dynamics
      of body temperature as Trpa1(+/+) mice and showed no weakness in the tail skin
      vasoconstriction response or thermogenic response to cold. In rats, the effects
      of pharmacological blockade were studied by using two chemically unrelated TRPA1
      antagonists: the highly potent and selective compound A967079, which had been
      characterized earlier, and the relatively new compound 43 ((4R)-1,2,3,4
      tetrahydro-4-[3-(3-methoxypropoxy)phenyl]-2-thioxo-5H-indeno[1,2-d]pyrimidin-5
      one), which we further characterized in the present study and found to be highly
      potent (IC50 against cold of ~8 nm) and selective. Intragastric administration of
      either antagonist at 30 mg/kg before severe (3 degrees C) cold exposure did not
      affect the thermoregulatory responses (deep body and tail skin temperatures) of
      rats, even though plasma concentrations of both antagonists well exceeded their
      IC50 value at the end of the experiment. In the same experimental setup, blocking
      the melastatin-8 (TRPM8) channel with AMG2850 (30 mg/kg) attenuated cold-defense
      mechanisms and led to hypothermia. We conclude that TRPA1 channels do not drive
      autonomic thermoregulatory responses to cold in rodents. 

PMID- 24671992
TI  - Mammalian target of rapamycin promotes oligodendrocyte differentiation,
      initiation and extent of CNS myelination.
AB  - Prior studies support a role for mammalian target of rapamycin (mTOR) signaling
      in oligodendrocyte differentiation and myelination. Here we use Cre-recombinase
      driven by the CNP promoter to generate a mouse line with oligodendrocyte-specific
      knockdown of mTOR (mTOR cKO) in the CNS. We provide evidence that mTOR is
      necessary for proper oligodendrocyte differentiation and myelination in the
      spinal cord. Specifically, the number of mature oligodendrocytes was reduced, and
      the initiation and extent of myelination were impaired during spinal cord
      development. Consistent with these data, myelin protein expression, including
      myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein,
      and myelin-associated glycoprotein, was delayed in the spinal cord.
      Hypomyelination of the spinal cord persisted into adulthood, as did the reduction
      in numbers of mature oligodendrocytes. In the cortex, the structure of myelin
      appeared normal during development and in the adult; however, myelin protein
      expression was delayed during development and was abnormal in the adult. Myelin
      basic protein was significantly reduced in all regions at postnatal day 25. These
      data demonstrate that mTOR promotes oligodendrocyte differentiation and CNS
      myelination in vivo and show that the requirement for mTOR varies by region with
      the spinal cord most dependent on mTOR. 

PMID- 24671993
TI  - Conditional ablation of raptor or rictor has differential impact on
      oligodendrocyte differentiation and CNS myelination.
AB  - During CNS development, oligodendrocytes, the myelinating glia of the CNS,
      progress through multiple transitory stages before terminating into fully mature
      cells. Oligodendrocyte differentiation and myelination is a tightly regulated
      process requiring extracellular signals to converge to elicit specific
      translational and transcriptional changes. Our lab has previously shown that the
      protein kinases, Akt and mammalian Target of Rapamycin (mTOR), are important
      regulators of CNS myelination in vivo. mTOR functions through two distinct
      complexes, mTOR complex 1 (mTORC1) and mTORC2, by binding to either Raptor or
      Rictor, respectively. To establish whether the impact of mTOR on CNS myelination
      results from unique functions of mTORC1 or mTORC2 during CNS myelination, we
      conditionally ablated either Raptor or Rictor in the oligodendrocyte lineage, in
      vivo. We show that Raptor (mTORC1) is a positive regulator of developmental CNS
      mouse myelination when mTORC2 is functional, whereas Rictor (mTORC2) ablation has
      a modest positive effect on oligodendrocyte differentiation, and very little
      effect on myelination, when mTORC1 is functional. Also, we show that loss of
      Raptor in oligodendrocytes results in differential dysmyelination in specific
      areas of the CNS, with the greatest impact on spinal cord myelination. 

PMID- 24671994
TI  - Selective localization of arc mRNA in dendrites involves activity- and
      translation-dependent mRNA degradation.
AB  - Arc is an immediate early gene that is unique among neuronal mRNAs because its
      transcripts are transported into dendrites and accumulate near activated
      synapses, presumably to be translated locally. These qualities pose Arc as
      playing an important, yet not fully understood, role in the activity-dependent
      modifications of synapses that are thought to underlie memory storage. Here we
      show in vivo in rats that newly synthesized Arc mRNA accumulates at activated
      synapses and that synaptic activity simultaneously triggers mRNA decay that
      eliminates Arc mRNA from inactive dendritic domains. Arc mRNA degradation occurs
      throughout the dendrite and requires both NMDA receptor activation and active
      translation. Synaptic activation did not lead to decreases in another dendritic
      mRNA (alphaCaMKII), indicating that there is not a general activation of mRNA
      degradation in dendrites. These data reveal a novel mechanism for controlling
      mRNA distribution within dendrites and highlight activity-dependent mRNA
      degradation as a regulatory process involved in synaptic plasticity. 

PMID- 24671995
TI  - Coordinated regulation of dendrite arborization by epigenetic factors CDYL and
      EZH2.
AB  - Dendritic arborization is one of the key determinants of precise circuits for
      information processing in neurons. Unraveling the molecular mechanisms underlying
      dendrite morphogenesis is critical to understanding the establishment of neuronal
      connections. Here, using gain- and loss-of-function approaches, we defined the
      chromodomain protein and transcription corepressor chromodomain Y-like (CDYL)
      protein as a negative regulator of dendrite morphogenesis in rat/mouse
      hippocampal neurons both in vitro and in vivo. Overexpressing CDYL decreased,
      whereas knocking it down increased, the dendritic complexity of the primary
      cultured rat neurons. High-throughput DNA microarray screening identified a
      number of CDYL downstream target genes, including the brain-derived neurotrophic
      factor (BDNF). Knock-down of CDYL in neuronal cells led to increased expression
      of BDNF, which is primarily responsible for CDYL's effects on dendrite patterns.
      Mechanistically, CDYL interacts with EZH2, the catalytic subunit of Polycomb
      Repressive Complex 2 (PRC2), directly and recruits the H3K27 methyltransferase
      activity to the promoter region of the BDNF gene. In doing so, CDYL and EZH2
      coordinately restrict dendrite morphogenesis in an interdependent manner.
      Finally, we found that neural activity increased dendritic complexity through
      degradation of CDYL protein to unleash its inhibition on BDNF. These results
      link, for the first time, the epigenetic regulators CDYL and EZH2 to dendrite
      morphogenesis and might shed new light on our understanding of the regulation of
      the neurodevelopment. 

PMID- 24671996
TI  - A major external source of cholinergic innervation of the striatum and nucleus
      accumbens originates in the brainstem.
AB  - Cholinergic transmission in the striatal complex is critical for the modulation
      of the activity of local microcircuits and dopamine release. Release of
      acetylcholine has been considered to originate exclusively from a subtype of
      striatal interneuron that provides widespread innervation of the striatum.
      Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental
      (LDT) nuclei indirectly influence the activity of the dorsal striatum and nucleus
      accumbens through their innervation of dopamine and thalamic neurons, which in
      turn converge at the same striatal levels. Here we show that cholinergic neurons
      in the brainstem also provide a direct innervation of the striatal complex. By
      the expression of fluorescent proteins in choline acetyltransferase
      (ChAT)::Cre(+) transgenic rats, we selectively labeled cholinergic neurons in the
      rostral PPN, caudal PPN, and LDT. We show that cholinergic neurons
      topographically innervate wide areas of the striatal complex: rostral PPN
      preferentially innervates the dorsolateral striatum, and LDT preferentially
      innervates the medial striatum and nucleus accumbens core in which they
      principally form asymmetric synapses. Retrograde labeling combined with
      immunohistochemistry in wild-type rats confirmed the topography and cholinergic
      nature of the projection. Furthermore, transynaptic gene activation and
      conventional double retrograde labeling suggest that LDT neurons that innervate
      the nucleus accumbens also send collaterals to the thalamus and the dopaminergic
      midbrain, thus providing both direct and indirect projections, to the striatal
      complex. The differential activity of cholinergic interneurons and cholinergic
      neurons of the brainstem during reward-related paradigms suggest that the two
      systems play different but complementary roles in the processing of information
      in the striatum. 

PMID- 24671997
TI  - MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal
      plasticity.
AB  - The methyl-DNA binding protein MeCP2 is emerging as an important regulator of
      drug reinforcement processes. Psychostimulants induce phosphorylation of MeCP2 at
      Ser421; however, the functional significance of this posttranslational
      modification for addictive-like behaviors was unknown. Here we show that MeCP2
      Ser421Ala knock-in mice display both a reduced threshold for the induction of
      locomotor sensitization by investigator-administered amphetamine and enhanced
      behavioral sensitivity to the reinforcing properties of self-administered
      cocaine. These behavioral differences were accompanied in the knock-in mice by
      changes in medium spiny neuron intrinsic excitability and nucleus accumbens gene
      expression typically observed in association with repeated exposure to these
      drugs. These data show that phosphorylation of MeCP2 at Ser421 functions to limit
      the circuit plasticities in the nucleus accumbens that underlie addictive-like
      behaviors. 

PMID- 24671998
TI  - Effect of maternal care on hearing onset induced by developmental changes in the
      auditory periphery.
AB  - Handling (H) and cross-fostering (CF) rodent pups during postnatal development
      triggers changes in maternal behavior which in turn trigger long-term
      physiological changes in the offspring. However, less is known about the short
      term effects of H and CF on infant development. In this study we hypothesized
      that manipulations of maternal care affect the onset of hearing in Wistar rats.
      To test this hypothesis we obtained auditory brainstem responses (ABRs) and micro
      CT x-ray scans to measure changes in the development of the auditory periphery in
      H and CF pups manipulated at postnatal day (P)1, P5, or P9. We found evidence of
      changes in hearing development in H and CF pups compared with naive pups,
      including changes in the percentage of animals with ABRs during development, a
      decrease in ABR thresholds between P13 and P15, and anatomical results consistent
      with an accelerated formation of the middle ear cavity and opening of the ear
      canal. Biochemical measurements showed elevated levels of thyroid hormone in
      plasma from naive and CF pups. These results provide evidence that manipulations
      of maternal care accelerate hearing onset in Wistar rats. Understanding the
      mechanisms by which maternal care affects hearing onset opens new opportunities
      to study experience-dependent development of mammalian hearing. 

PMID- 24671999
TI  - Dendritic inhibition provided by interneuron-specific cells controls the firing
      rate and timing of the hippocampal feedback inhibitory circuitry.
AB  - In cortical networks, different types of inhibitory interneurons control the
      activity of glutamatergic principal cells and GABAergic interneurons. Principal
      neurons represent the major postsynaptic target of most interneurons; however, a
      population of interneurons that is dedicated to the selective innervation of
      GABAergic cells exists in the CA1 area of the hippocampus. The physiological
      properties of these cells and their functional relevance for network computations
      remain unknown. Here, we used a combination of dual simultaneous patch-clamp
      recordings and targeted optogenetic stimulation in acute mouse hippocampal slices
      to examine how one class of interneuron-specific (IS) cells controls the activity
      of its GABAergic targets. We found that type 3 IS (IS3) cells that coexpress the
      vasoactive intestinal polypeptide (VIP) and calretinin contact several distinct
      types of interneurons within the hippocampal CA1 stratum oriens/alveus (O/A),
      with preferential innervation of oriens-lacunosum moleculare cells (OLMs) through
      dendritic synapses. In contrast, VIP-positive basket cells provided perisomatic
      inhibition to CA1 pyramidal neurons with the asynchronous GABA release and were
      not connected with O/A interneurons. Furthermore, unitary IPSCs recorded at IS3
      OLM synapses had a small amplitude and low release probability but summated
      efficiently during high-frequency firing of IS3 interneurons. Moreover, the
      synchronous generation of a single spike in several IS cells that converged onto
      a single OLM controlled the firing rate and timing of OLM interneurons.
      Therefore, dendritic inhibition originating from IS cells is needed for the
      flexible activity-dependent recruitment of OLM interneurons for feedback
      inhibition. 

PMID- 24672000
TI  - Task-dependent decoding of speaker and vowel identity from auditory cortical
      response patterns.
AB  - Selective attention to relevant sound properties is essential for everyday
      listening situations. It enables the formation of different perceptual
      representations of the same acoustic input and is at the basis of flexible and
      goal-dependent behavior. Here, we investigated the role of the human auditory
      cortex in forming behavior-dependent representations of sounds. We used single
      trial fMRI and analyzed cortical responses collected while subjects listened to
      the same speech sounds (vowels /a/, /i/, and /u/) spoken by different speakers
      (boy, girl, male) and performed a delayed-match-to-sample task on either speech
      sound or speaker identity. Univariate analyses showed a task-specific activation
      increase in the right superior temporal gyrus/sulcus (STG/STS) during speaker
      categorization and in the right posterior temporal cortex during vowel
      categorization. Beyond regional differences in activation levels, multivariate
      classification of single trial responses demonstrated that the success with which
      single speakers and vowels can be decoded from auditory cortical activation
      patterns depends on task demands and subject's behavioral performance.
      Speaker/vowel classification relied on distinct but overlapping regions across
      the (right) mid-anterior STG/STS (speakers) and bilateral mid-posterior STG/STS
      (vowels), as well as the superior temporal plane including Heschl's gyrus/sulcus.
      The task dependency of speaker/vowel classification demonstrates that the
      informative fMRI response patterns reflect the top-down enhancement of
      behaviorally relevant sound representations. Furthermore, our findings suggest
      that successful selection, processing, and retention of task-relevant sound
      properties relies on the joint encoding of information across early and higher
      order regions of the auditory cortex. 

PMID- 24672001
TI  - Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer
      proteins in the hippocampus of Ube3A hemizygous mice modeling angelman syndrome.
AB  - Angelman syndrome (AS) is caused by the loss of Ube3A, an ubiquitin ligase that
      commits specific proteins to proteasomal degradation. How this defect causes
      autism and other pathological phenotypes associated with AS is unknown. Long-term
      depression (LTD) of excitatory synaptic transmission mediated by type 5
      metabotropic glutamate (mGlu5) receptors was enhanced in hippocampal slices of
      Ube3A(m-/p+) mice, which model AS. No changes were found in NMDA-dependent LTD
      induced by low-frequency stimulation. mGlu5 receptor-dependent LTD in AS mice was
      sensitive to the protein synthesis inhibitor anisomycin, and relied on the same
      signaling pathways as in wild-type mice, e.g., the mitogen-activated protein
      kinase (MAPK) pathway, the phosphatidylinositol-3-kinase (PI3K)/mammalian target
      of rapamycine pathway, and protein tyrosine phosphatase. Neither the stimulation
      of MAPK and PI3K nor the increase in Arc (activity-regulated cytoskeleton
      associated protein) levels in response to mGlu5 receptor activation were abnormal
      in hippocampal slices from AS mice compared with wild-type mice. mGlu5 receptor
      expression and mGlu1/5 receptor-mediated polyphosphoinositide hydrolysis were
      also unchanged in the hippocampus of AS mice. In contrast, AS mice showed a
      reduced expression of the short Homer protein isoform Homer 1a, and an increased
      coupling of mGlu5 receptors to Homer 1b/c proteins in the hippocampus. These
      findings support the link between Homer proteins and monogenic autism, and lay
      the groundwork for the use of mGlu5 receptor antagonists in AS. 

PMID- 24672002
TI  - Altered neural processing of the need to stop in young adults at risk for
      stimulant dependence.
AB  - Identification of neurocognitive predictors of substance dependence is an
      important step in developing approaches to prevent addiction. Given evidence of
      inhibitory control deficits in substance abusers (Monterosso et al., 2005; Fu et
      al., 2008; Lawrence et al., 2009; Tabibnia et al., 2011), we examined neural
      processing characteristics in human occasional stimulant users (OSU), a
      population at risk for dependence. A total of 158 nondependent OSU and 47
      stimulant-naive control subjects (CS) were recruited and completed a stop signal
      task while undergoing functional magnetic resonance imaging (fMRI). A Bayesian
      ideal observer model was used to predict probabilistic expectations of inhibitory
      demand, P(stop), on a trial-to-trial basis, based on experienced trial history.
      Compared with CS, OSU showed attenuated neural activation related to P(stop)
      magnitude in several areas, including left prefrontal cortex and left caudate.
      OSU also showed reduced neural activation in the dorsal anterior cingulate cortex
      (dACC) and right insula in response to an unsigned Bayesian prediction error
      representing the discrepancy between stimulus outcome and the predicted
      probability of a stop trial. These results indicate that, despite minimal overt
      behavioral manifestations, OSU use fewer brain processing resources to predict
      and update the need for response inhibition, processes that are critical for
      adjusting and optimizing behavioral performance, which may provide a biomarker
      for the development of substance dependence. 

PMID- 24672003
TI  - microRNA-206 in rat medial prefrontal cortex regulates BDNF expression and
      alcohol drinking.
AB  - Escalation of voluntary alcohol consumption is a hallmark of alcoholism, but its
      neural substrates remain unknown. In rats, escalation occurs following prolonged
      exposure to cycles of alcohol intoxication, and is associated with persistent,
      wide-ranging changes in gene expression within the medial prefrontal cortex
      (mPFC). Here, we examined whether induction of microRNA (miR) 206 in mPFC
      contributes to escalated alcohol consumption. Following up on a microarray
      screen, quantitative real-time reverse transcription PCR (qPCR) confirmed that a
      history of dependence results in persistent (>3weeks) up-regulation of miR-206
      expression in the mPFC, but not in the ventral tegmental area, amygdala, or
      nucleus accumbens. Viral-mediated overexpression of miR-206 in the mPFC of
      nondependent rats reproduced the escalation of alcohol self-administration seen
      following a history of dependence and significantly inhibited BDNF expression.
      Bioinformatic analysis identified three conserved target sites for miR-206 in the
      3'-UTR of the rat BDNF transcript. Accordingly, BDNF was downregulated in post
      dependent rats on microarray analysis, and this was confirmed by qPCR. In vitro,
      BDNF expression was repressed by miR-206 but not miR-9 in a 3'-UTR reporter
      assay, confirming BDNF as a functional target of miR-206. Mutation analysis
      showed that repression was dependent on the presence of all three miR-206 target
      sites in the BDNF 3'-UTR. Inhibition of miR-206 expression in differentiated rat
      cortical primary neurons significantly increased secreted levels of BDNF. In
      conclusion, recruitment of miR-206 in the mPFC contributes to escalated alcohol
      consumption following a history of dependence, with BDNF as a possible mediator
      of its action. 

PMID- 24672004
TI  - Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus.
AB  - Metabotropic glutamate receptor 5 (mGluR5) is widely expressed throughout the CNS
      and participates in regulating neuronal function and synaptic transmission.
      Recent work in the striatum led to the groundbreaking discovery that
      intracellular mGluR5 activation drives unique signaling pathways, including
      upregulation of ERK1/2, Elk-1 (Jong et al., 2009) and Arc (Kumar et al., 2012).
      To determine whether mGluR5 signals from intracellular membranes of other cell
      types, such as excitatory pyramidal neurons in the hippocampus, we used
      dissociated rat CA1 hippocampal cultures and slice preparations to localize and
      characterize endogenous receptors. As in the striatum, CA1 neurons exhibited an
      abundance of mGluR5 both on the cell surface and intracellular membranes,
      including the endoplasmic reticulum and the nucleus where it colocalized with the
      sodium-dependent excitatory amino acid transporter, EAAT3. Inhibition of EAAT3 or
      sodium-free buffer conditions prevented accumulations of radiolabeled agonist.
      Using a pharmacological approach to isolate different pools of mGluR5, both
      intracellular and cell surface receptors induced oscillatory Ca(2+) responses in
      dissociated CA1 neurons; however, only intracellular mGluR5 activation triggered
      sustained high amplitude Ca(2+) rises in dendrites. Consistent with the notion
      that mGluR5 can signal from intracellular membranes, uncaging glutamate on a CA1
      dendrite led to a local Ca(2+) rise, even in the presence of ionotropic and cell
      surface metabotropic receptor inhibitors. Finally, activation of intracellular
      mGluR5 alone mediated both electrically induced and chemically induced long-term
      depression, but not long-term potentiation, in acute hippocampal slices. These
      data suggest a physiologically relevant and important role for intracellular
      mGluR5 in hippocampal synaptic plasticity. 

PMID- 24672006
TI  - Goal-dependent modulation of fast feedback responses in primary motor cortex.
AB  - Many human studies have demonstrated that rapid motor responses (i.e., muscle
      stretch reflexes) to mechanical perturbations can be modified by a participant's
      intended response. Here, we used a novel experimental paradigm to investigate the
      neural mechanisms that underlie such goal-dependent modulation. Two monkeys
      positioned their hand in a central area against a constant load and responded to
      mechanical perturbations by quickly placing their hand into visually defined
      spatial targets. The perturbation was chosen to excite a particular proximal arm
      muscle or isolated neuron in primary motor cortex and two targets were placed so
      that the hand was pushed away from one target (OUT target) and toward the other
      (IN target). We chose these targets because they produced behavioral responses
      analogous to the classical verbal instructions used in human studies. A third
      centrally located target was used to examine responses with a constant goal. Arm
      muscles and neurons robustly responded to the perturbation and showed clear goal
      dependent responses ~35 and 70 ms after perturbation onset, respectively. Most M1
      neurons and all muscles displayed larger perturbation-related responses for the
      OUT target than the IN target. However, a substantial number of M1 neurons showed
      more complex patterns of target-dependent modulation not seen in muscles,
      including greater activity for the IN target than the OUT target, and changes in
      target preference over time. Together, our results reveal complex goal-dependent
      modulation of fast feedback responses in M1 that are present early enough to
      account for goal-dependent stretch responses in arm muscles. 

PMID- 24672005
TI  - Efferent feedback slows cochlear aging.
AB  - The inner ear receives two types of efferent feedback from the brainstem: one
      pathway provides gain control on outer hair cells' contribution to cochlear
      amplification, and the other modulates the excitability of the cochlear nerve.
      Although efferent feedback can protect hair cells from acoustic injury and
      thereby minimize noise-induced permanent threshold shifts, most prior studies
      focused on high-intensity exposures (>100 dB SPL). Here, we show that efferents
      are essential for long-term maintenance of cochlear function in mice aged 1 year
      post-de-efferentation without purposeful acoustic overexposure. Cochlear de
      efferentation was achieved by surgical lesion of efferent pathways in the
      brainstem and was assessed by quantitative analysis of immunostained efferent
      terminals in outer and inner hair cell areas. The resultant loss of efferent
      feedback accelerated the age-related amplitude reduction in cochlear neural
      responses, as seen in auditory brainstem responses, and increased the loss of
      synapses between hair cells and the terminals of cochlear nerve fibers, as seen
      in confocal analysis of the organ of Corti immunostained for presynaptic and
      postsynaptic markers. This type of neuropathy, also seen after moderate noise
      exposure, has been termed "hidden hearing loss", because it does not affect
      thresholds, but can be seen in the suprathreshold amplitudes of cochlear neural
      responses, and likely causes problems with hearing in a noisy environment, a
      classic symptom of age-related hearing loss in humans. Since efferent reflex
      strength varies among individuals and can be measured noninvasively, a weak
      reflex may be an important risk factor, and prognostic indicator, for age-related
      hearing impairment. 

PMID- 24672007
TI  - Preferential involvement by nucleus accumbens shell in mediating probabilistic
      learning and reversal shifts.
AB  - Different subregions of nucleus accumbens (NAc) have been implicated in reward
      seeking, promoting flexible approach responses, suppressing nonrewarded actions,
      and facilitating shifts between different discrimination strategies.
      Interestingly, the NAc does not appear to mediate shifting between stimulus
      reward associations (i.e., reversal learning) when reinforcement is predictable.
      How these nuclei may facilitate flexible response strategies when reward delivery
      is uncertain remains unclear. We investigated the effects of inactivation of the
      NAc shell and core on probabilistic reversal learning using an operant task
      wherein a "correct" response delivered reward on 80% of trials, and an
      "incorrect" response was reinforced on 20% of trials. Reinforcement contingencies
      were reversed repeatedly within a session. In well-trained rats, shell
      inactivation reduced the number of reversals completed and selectively reduced
      win-stay behavior. This impairment was apparent during the first discrimination,
      indicating a more general deficit in the use of probabilistic reward feedback to
      guide action selection. Shell inactivation also impaired reversal performance on
      a similar task where correct/incorrect choices always/never delivered reward.
      However, this impairment only emerged after both levers had been associated with
      reward. Inactivation of NAc core did not impair reversal performance but
      increased latencies to approach the response levers. These results suggest the
      NAc shell and core facilitate reward seeking in a distinct yet complementary
      manner when the relationship between specific actions and reward is uncertain or
      ambiguous and cognitive flexibility is required. The core promotes approach
      toward reward-associated stimuli, whereas the shell refines response selection to
      those specific actions more likely to yield reward. 

PMID- 24672008
TI  - Circadian perinatal photoperiod has enduring effects on retinal dopamine and
      visual function.
AB  - Visual system development depends on neural activity, driven by intrinsic and
      light-sensitive mechanisms. Here, we examined the effects on retinal function due
      to exposure to summer- and winter-like circadian light cycles during development
      and adulthood. Retinal light responses, visual behaviors, dopamine content,
      retinal morphology, and gene expression were assessed in mice reared in seasonal
      photoperiods consisting of light/dark cycles of 8:16, 16:8, and 12:12 h,
      respectively. Mice exposed to short, winter-like, light cycles showed enduring
      deficits in photopic retinal light responses and visual contrast sensitivity, but
      only transient changes were observed for scotopic measures. Dopamine levels were
      significantly lower in short photoperiod mice, and dopaminergic agonist treatment
      rescued the photopic light response deficits. Tyrosine hydroxylase and Early
      Growth Response factor-1 mRNA expression were reduced in short photoperiod
      retinas. Therefore, seasonal light cycles experienced during retinal development
      and maturation have lasting influence on retinal and visual function, likely
      through developmental programming of retinal dopamine. 

PMID- 24672009
TI  - Representation of spatial information in key areas of the descending pain
      modulatory system.
AB  - Behavioral studies have demonstrated that descending pain modulation can be
      spatially specific, as is evident in placebo analgesia, which can be limited to
      the location at which pain relief is expected. This suggests that higher-order
      cortical structures of the descending pain modulatory system carry spatial
      information about the site of stimulation. Here, we used functional magnetic
      resonance imaging and multivariate pattern analysis in 15 healthy human
      volunteers to test whether spatial information of painful stimuli is represented
      in areas of the descending pain modulatory system. We show that the site of
      nociceptive stimulation (arm or leg) can be successfully decoded from local
      patterns of brain activity during the anticipation and receipt of painful
      stimulation in the rostral anterior cingulate cortex, the dorsolateral prefrontal
      cortices, and the contralateral parietal operculum. These results demonstrate
      that information regarding the site of nociceptive stimulation is represented in
      these brain regions. Attempts to predict arm and leg stimulation from the
      periaqueductal gray, control regions (e.g., white matter) or the control time
      interval in the intertrial phase did not allow for classifications above chance
      level. This finding represents an important conceptual advance in the
      understanding of endogenous pain control mechanisms by bridging the gap between
      previous behavioral and neuroimaging studies, suggesting a spatial specificity of
      endogenous pain control. 

PMID- 24672010
TI  - ATM-dependent phosphorylation of MEF2D promotes neuronal survival after DNA
      damage.
AB  - Mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a kinase
      critical for the normal DNA damage response, cause the neurodegenerative disorder
      ataxia-telangiectasia (AT). The substrates of ATM in the brain are poorly
      understood. Here we demonstrate that ATM phosphorylates and activates the
      transcription factor myocyte enhancer factor 2D (MEF2D), which plays a critical
      role in promoting survival of cerebellar granule cells. ATM associates with MEF2D
      after DNA damage and phosphorylates the transcription factor at four ATM
      consensus sites. Knockdown of endogenous MEF2D with a short-hairpin RNA (shRNA)
      increases sensitivity to etoposide-induced DNA damage and neuronal cell death.
      Interestingly, substitution of endogenous MEF2D with an shRNA-resistant
      phosphomimetic MEF2D mutant protects cerebellar granule cells from cell death
      after DNA damage, whereas an shRNA-resistant nonphosphorylatable MEF2D mutant
      does not. In vivo, cerebella in Mef2d knock-out mice manifest increased
      susceptibility to DNA damage. Together, our results show that MEF2D is a
      substrate for phosphorylation by ATM, thus promoting survival in response to DNA
      damage. Moreover, dysregulation of the ATM-MEF2D pathway may contribute to
      neurodegeneration in AT. 

PMID- 24672011
TI  - Cholinergic inputs from Basal forebrain add an excitatory bias to odor coding in
      the olfactory bulb.
AB  - Cholinergic modulation of central circuits is associated with active sensation,
      attention, and learning, yet the neural circuits and temporal dynamics underlying
      cholinergic effects on sensory processing remain unclear. Understanding the
      effects of cholinergic modulation on particular circuits is complicated by the
      widespread projections of cholinergic neurons to telencephalic structures that
      themselves are highly interconnected. Here we examined how cholinergic
      projections from basal forebrain to the olfactory bulb (OB) modulate output from
      the first stage of sensory processing in the mouse olfactory system. By
      optogenetically activating their axons directly in the OB, we found that
      cholinergic projections from basal forebrain regulate OB output by increasing the
      spike output of presumptive mitral/tufted cells. Cholinergic stimulation
      increased mitral/tufted cell spiking in the absence of inhalation-driven sensory
      input and further increased spiking responses to inhalation of odorless air and
      to odorants. This modulation was rapid and transient, was dependent on local
      cholinergic signaling in the OB, and differed from modulation by optogenetic
      activation of cholinergic neurons in basal forebrain, which led to a mixture of
      mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic
      enhancement of mitral/tufted cell odorant responses was robust and occurred
      independent of the strength or even polarity of the odorant-evoked response,
      indicating that cholinergic modulation adds an excitatory bias to mitral/tufted
      cells as opposed to increasing response gain or sharpening response spectra.
      These results are consistent with a role for the basal forebrain cholinergic
      system in dynamically regulating the sensitivity to or salience of odors during
      active sensing of the olfactory environment. 

PMID- 24672012
TI  - Differential coding of conspecific vocalizations in the ventral auditory cortical
      stream.
AB  - The mammalian auditory cortex integrates spectral and temporal acoustic features
      to support the perception of complex sounds, including conspecific vocalizations.
      Here we investigate coding of vocal stimuli in different subfields in macaque
      auditory cortex. We simultaneously measured auditory evoked potentials over a
      large swath of primary and higher order auditory cortex along the supratemporal
      plane in three animals chronically using high-density microelectrocorticographic
      arrays. To evaluate the capacity of neural activity to discriminate individual
      stimuli in these high-dimensional datasets, we applied a regularized multivariate
      classifier to evoked potentials to conspecific vocalizations. We found a gradual
      decrease in the level of overall classification performance along the caudal to
      rostral axis. Furthermore, the performance in the caudal sectors was similar
      across individual stimuli, whereas the performance in the rostral sectors
      significantly differed for different stimuli. Moreover, the information about
      vocalizations in the caudal sectors was similar to the information about
      synthetic stimuli that contained only the spectral or temporal features of the
      original vocalizations. In the rostral sectors, however, the classification for
      vocalizations was significantly better than that for the synthetic stimuli,
      suggesting that conjoined spectral and temporal features were necessary to
      explain differential coding of vocalizations in the rostral areas. We also found
      that this coding in the rostral sector was carried primarily in the theta
      frequency band of the response. These findings illustrate a progression in neural
      coding of conspecific vocalizations along the ventral auditory pathway. 

PMID- 24672013
TI  - Human EEG uncovers latent generalizable rule structure during learning.
AB  - Human cognition is flexible and adaptive, affording the ability to detect and
      leverage complex structure inherent in the environment and generalize this
      structure to novel situations. Behavioral studies show that humans impute
      structure into simple learning problems, even when this tendency affords no
      behavioral advantage. Here we used electroencephalography to investigate the
      neural dynamics indicative of such incidental latent structure. Event-related
      potentials over lateral prefrontal cortex, typically observed for instructed task
      rules, were stratified according to individual participants' constructed rule
      sets. Moreover, this individualized latent rule structure could be independently
      decoded from multielectrode pattern classification. Both neural markers were
      predictive of participants' ability to subsequently generalize rule structure to
      new contexts. These EEG dynamics reveal that the human brain spontaneously
      constructs hierarchically structured representations during learning of simple
      task rules. 

PMID- 24672014
TI  - Amphetamine potentiates the effects of beta-phenylethylamine through activation
      of an amine-gated chloride channel.
AB  - beta-Phenylethylamine (betaPEA) is a trace amine present in the CNS of all
      animals tested to date. However, its function is still not fully understood.
      betaPEA has been suggested to function as a neurotransmitter and/or to mimic the
      effect of amphetamine (Amph). In support of the latter is the observation that
      betaPEA and Amph produce similar but not identical behaviors. Here, we show that
      betaPEA, like Amph, activates the dopamine transporter and the amine-gated
      chloride channel LGC-55 to generate behaviors in Caenorhabditis elegans. However,
      although Amph-induced behaviors occurred gradually during 10 min of treatment,
      betaPEA induced maximal effects within 1 min. In vitro data demonstrate that
      betaPEA activates the LGC-55 more efficiently than Amph (Km = 9 and 152 MUm,
      respectively) and generates saturating currents that are 10 times larger than
      those produced by Amph. These results suggest that activation of LGC-55 mostly
      accounts for the behavioral effects reached after 1 min of treatment with
      betaPEA. Importantly, our in vitro and in vivo data show that Amph increases the
      effects induced by betaPEA on the LGC-55, indicating that Amph potentiates the
      effects generated by the biogenic amine betaPEA. Together, our data not only
      identify a new target for betaPEA, but also offer a novel mechanism of action of
      Amph. In addition, our results highlight C. elegans as a powerful genetic model
      for studying the effects of biogenic and synthetic amines both at the molecular
      and behavioral levels. 

PMID- 24672017
TI  - Mechanisms of dopamine D1 receptor-mediated ERK1/2 activation in the parkinsonian
      striatum and their modulation by metabotropic glutamate receptor type 5.
AB  - In animal models of Parkinson's disease, striatal overactivation of ERK1/2 via
      dopamine (DA) D1 receptors is the hallmark of a supersensitive molecular response
      associated with dyskinetic behaviors. Here we investigate the pathways involved
      in D1 receptor-dependent ERK1/2 activation using acute striatal slices from
      rodents with unilateral 6-hydroxydopamine (6-OHDA) lesions. Application of the
      dopamine D1-like receptor agonist SKF38393 induced ERK1/2 phosphorylation and
      downstream signaling in the DA-denervated but not the intact striatum. This
      response was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent
      of ionotropic glutamate receptors but blocked by antagonists of L-type calcium
      channels. Coapplication of an antagonist of metabotropic glutamate receptor type
      5 (mGluR5) or its downstream signaling molecules (PLC, PKC, IP3 receptors)
      markedly attenuated SKF38393-induced ERK1/2 activation. The role of striatal
      mGluR5 in D1-dependent ERK1/2 activation was confirmed in vivo in 6-OHDA-lesioned
      animals treated systemically with SKF38393. In one experiment, local infusion of
      the mGluR5 antagonist MTEP in the DA-denervated rat striatum attenuated the
      activation of ERK1/2 signaling by SKF38393. In another experiment, 6-OHDA lesions
      were applied to transgenic mice with a cell-specific knockdown of mGluR5 in D1
      receptor-expressing neurons. These mice showed a blunted striatal ERK1/2
      activation in response to SFK38393 treatment. Our results reveal that D1
      dependent ERK1/2 activation in the DA-denervated striatum depends on a complex
      interaction between PKA- and Ca(2+)-dependent signaling pathways that is
      critically modulated by striatal mGluR5. 

PMID- 24672015
TI  - A unified mathematical framework for coding time, space, and sequences in the
      hippocampal region.
AB  - The medial temporal lobe (MTL) is believed to support episodic memory, vivid
      recollection of a specific event situated in a particular place at a particular
      time. There is ample neurophysiological evidence that the MTL computes location
      in allocentric space and more recent evidence that the MTL also codes for time.
      Space and time represent a similar computational challenge; both are variables
      that cannot be simply calculated from the immediately available sensory
      information. We introduce a simple mathematical framework that computes functions
      of both spatial location and time as special cases of a more general computation.
      In this framework, experience unfolding in time is encoded via a set of leaky
      integrators. These leaky integrators encode the Laplace transform of their input.
      The information contained in the transform can be recovered using an
      approximation to the inverse Laplace transform. In the temporal domain, the
      resulting representation reconstructs the temporal history. By integrating
      movements, the equations give rise to a representation of the path taken to
      arrive at the present location. By modulating the transform with information
      about allocentric velocity, the equations code for position of a landmark.
      Simulated cells show a close correspondence to neurons observed in various
      regions for all three cases. In the temporal domain, novel secondary analyses of
      hippocampal time cells verified several qualitative predictions of the model. An
      integrated representation of spatiotemporal context can be computed by taking
      conjunctions of these elemental inputs, leading to a correspondence with
      conjunctive neural representations observed in dorsal CA1. 

PMID- 24672018
TI  - Integrative moral judgment: dissociating the roles of the amygdala and
      ventromedial prefrontal cortex.
AB  - A decade's research highlights a critical dissociation between automatic and
      controlled influences on moral judgment, which is subserved by distinct neural
      structures. Specifically, negative automatic emotional responses to
      prototypically harmful actions (e.g., pushing someone off of a footbridge)
      compete with controlled responses favoring the best consequences (e.g., saving
      five lives instead of one). It is unknown how such competitions are resolved to
      yield "all things considered" judgments. Here, we examine such integrative moral
      judgments. Drawing on insights from research on self-interested, value-based
      decision-making in humans and animals, we test a theory concerning the respective
      contributions of the amygdala and ventromedial prefrontal cortex (vmPFC) to moral
      judgment. Participants undergoing fMRI responded to moral dilemmas, separately
      evaluating options for their utility (Which does the most good?), emotional
      aversiveness (Which feels worse?), and overall moral acceptability. Behavioral
      data indicate that emotional aversiveness and utility jointly predict "all things
      considered" integrative judgments. Amygdala response tracks the emotional
      aversiveness of harmful utilitarian actions and overall disapproval of such
      actions. During such integrative moral judgments, the vmPFC is preferentially
      engaged relative to utilitarian and emotional assessments. Amygdala-vmPFC
      connectivity varies with the role played by emotional input in the task, being
      the lowest for pure utilitarian assessments and the highest for pure emotional
      assessments. These findings, which parallel those of research on self-interested
      economic decision-making, support the hypothesis that the amygdala provides an
      affective assessment of the action in question, whereas the vmPFC integrates that
      signal with a utilitarian assessment of expected outcomes to yield "all things
      considered" moral judgments. 

PMID- 24672019
TI  - Cue-induced craving increases impulsivity via changes in striatal value signals
      in problem gamblers.
AB  - Impulsive behavior such as steep temporal discounting is a hallmark of addiction
      and is associated with relapse. In pathological gamblers, discounting may be
      further increased by the presence of gambling-related cues in the environment,
      but the extent to which the gambling relatedness of task settings affects reward
      responses in gambling addiction is debated. In the present study, human problem
      gamblers made choices between immediate rewards and individually tailored larger
      but-later rewards while visual gambling-related scenes were presented in the
      background. N = 17 participants were scanned using fMRI, whereas N = 5 additional
      participants completed a behavioral version of the task. Postscan craving ratings
      were acquired for each image, and behavioral and neuroimaging data were analyzed
      separately for high- and low-craving trials (median split analysis). Discounting
      was steeper for high versus low craving trials. Neuroimaging revealed a positive
      correlation with model-based subjective value in midbrain and striatum in low
      craving trials that was reversed in high-craving trials. These findings reveal a
      modulation of striatal reward responses in gamblers by addiction-related cues,
      and highlight a potentially important mechanism that may contribute to relapse.
      Cue-induced changes in striatal delayed reward signals may lead to increased
      discounting of future rewards, which might in turn affect the likelihood of
      relapse. 

PMID- 24672016
TI  - Discharge profiles across the sleep-waking cycle of identified cholinergic,
      GABAergic, and glutamatergic neurons in the pontomesencephalic tegmentum of the
      rat.
AB  - Distributed within the laterodorsal tegmental and pedunculopontine tegmental
      nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum
      have long been thought to play a critical role in stimulating cortical activation
      during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in
      promoting PS with muscle atonia. However, the discharge profile and thus precise
      roles of the cholinergic neurons have remained uncertain because they lie
      intermingled with GABAergic and glutamatergic neurons, which might also assume
      these roles. By applying juxtacellular recording and labeling in naturally
      sleeping-waking, head-fixed rats, we investigated the discharge profiles of
      histochemically identified cholinergic, GABAergic, and glutamatergic neurons in
      the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep
      wake states, cortical activity, and muscle tone. We found that all cholinergic
      neurons were maximally active during W and PS in positive correlation with fast
      (gamma) cortical activity, as "W/PS-max active neurons." Like cholinergic
      neurons, many GABAergic and glutamatergic neurons were also "W/PS-max active."
      Other GABAergic and glutamatergic neurons were "PS-max active," being minimally
      active during W and maximally active during PS in negative correlation with
      muscle tone. Conversely, some glutamatergic neurons were "W-max active," being
      maximally active during W and minimally active during PS in positive correlation
      with muscle tone. Through different discharge profiles, the cholinergic,
      GABAergic, and glutamatergic neurons of the LDT, SubLDT, and MPPT thus appear to
      play distinct roles in promoting W and PS with cortical activation, PS with
      muscle atonia, or W with muscle tone. 

PMID- 24672020
TI  - Counting on the motor system: rapid action planning reveals the format- and
      magnitude-dependent extraction of numerical quantity.
AB  - Symbolic numbers (e.g., "2") acquire their meaning by becoming linked to the core
      nonsymbolic quantities they represent (e.g., two items). However, the extent to
      which symbolic and nonsymbolic information converges onto the same internal core
      representations of quantity remains a point of considerable debate. As nearly all
      previous work on this topic has employed perceptual tasks requiring the conscious
      reporting of numerical magnitudes, here we question the extent to which numerical
      processing via the visual-motor system might shed further light on the
      fundamental basis of how different number formats are encoded. We show, using a
      rapid reaching task and a detailed analysis of initial arm trajectories, that
      there are key differences in how the quantity information extracted from symbolic
      Arabic numerals and nonsymbolic collections of discrete items are used to guide
      action planning. In particular, we found that the magnitude derived from discrete
      dots resulted in movements being biased by an amount directly proportional to the
      actual quantities presented whereas the magnitude derived from numerals resulted
      in movements being biased only by the relative (e.g., larger than) quantities
      presented. In addition, we found that initial motor plans were more sensitive to
      changes in numerical quantity within small (1-3) than large (5-15) number ranges,
      irrespective of their format (dots or numerals). In light of previous work, our
      visual-motor results clearly show that the processing of numerical quantity
      information is both format and magnitude dependent. 

PMID- 24672021
TI  - Emotion modulates eye movement patterns and subsequent memory for the gist and
      details of movie scenes.
AB  - A basic question in vision research regards where people look in complex scenes
      and how this influences their performance in various tasks. Previous studies with
      static images have demonstrated a close link between where people look and what
      they remember. Here, we examined the pattern of eye movements when participants
      watched neutral and emotional clips from Hollywood-style movies. Participants
      answered multiple-choice memory questions concerning visual and auditory scene
      details immediately upon viewing 1-min-long neutral or emotional movie clips.
      Fixations were more narrowly focused for emotional clips, and immediate memory
      for object details was worse compared to matched neutral scenes, implying
      preferential attention to emotional events. Although we found the expected
      correlation between where people looked and what they remembered for neutral
      clips, this relationship broke down for emotional clips. When participants were
      subsequently presented with key frames (static images) extracted from the movie
      clips such that presentation duration of the target objects (TOs) corresponding
      to the multiple-choice questions was matched and the earlier questions were
      repeated, more fixations were observed on the TOs, and memory performance also
      improved significantly, confirming that emotion modulates the relationship
      between gaze position and memory performance. Finally, in a long-term memory
      test, old/new recognition performance was significantly better for emotional
      scenes as compared to neutral scenes. Overall, these results are consistent with
      the hypothesis that emotional content draws eye fixations and strengthens memory
      for the scene gist while weakening encoding of peripheral scene details. 

PMID- 24672022
TI  - ESR investigation of sucrose radicals produced by 0.25-4.5 Gy doses of X-ray
      irradiation.
AB  - We investigated stable radicals produced by 0.25-4.5 Gy doses of X-ray
      irradiation of sucrose. Electron spin resonance (ESR) is able to observe the
      signal from sucrose irradiated at 0.25 Gy. The ESR signal intensity of the
      radicals is related to the accumulated dose, and it increases linearly with
      increasing absorbed dose. In addition, we examined the effect of dose rate (0.50
      1.5 Gy/min) on the signal intensity of the irradiated sucrose. The stable radical
      production did not exhibit dose rate dependence. In addition, the peak
      corresponding to the irradiated glucose was observed to increase more with
      increasing absorbed dose than the peak corresponding to irradiated fructose.
      Therefore, the present ESR results regarding the 0.25-4.5 Gy irradiation of
      sucrose provide new insights into a possible sucrose ESR dosimeter.

PMID- 24672023
TI  - The Rhinovirus subviral a-particle exposes 3'-terminal sequences of its genomic
      RNA.
AB  - Enteroviruses, which represent a large genus within the family Picornaviridae,
      undergo important conformational modifications during infection of the host cell.
      Once internalized by receptor-mediated endocytosis, receptor binding and/or the
      acidic endosomal environment triggers the native virion to expand and convert
      into the subviral (altered) A-particle. The A-particle is lacking the internal
      capsid protein VP4 and exposes N-terminal amphipathic sequences of VP1, allowing
      for its direct interaction with a lipid bilayer. The genomic single-stranded
      (+)RNA then exits through a hole close to a 2-fold axis of icosahedral symmetry
      and passes through a pore in the endosomal membrane into the cytosol, leaving
      behind the empty shell. We demonstrate that in vitro acidification of a prototype
      of the minor receptor group of common cold viruses, human rhinovirus A2 (HRV-A2),
      also results in egress of the poly(A) tail of the RNA from the A-particle, along
      with adjacent nucleotides totaling ~700 bases. However, even after hours of
      incubation at pH 5.2, 5'-proximal sequences remain inside the capsid. In
      contrast, the entire RNA genome is released within minutes of exposure to the
      acidic endosomal environment in vivo. This finding suggests that the exposed 3'
      poly(A) tail facilitates the positioning of the RNA exit site onto the putative
      channel in the lipid bilayer, thereby preventing the egress of viral RNA into the
      endosomal lumen, where it may be degraded. IMPORTANCE: For host cell infection, a
      virus transfers its genome from within the protective capsid into the cytosol;
      this requires modifications of the viral shell. In common cold viruses, exit of
      the RNA genome is prepared by the acidic environment in endosomes converting the
      native virion into the subviral A-particle. We demonstrate that acidification in
      vitro results in RNA exit starting from the 3'-terminal poly(A). However, the
      process halts as soon as about 700 bases have left the viral shell. Conversely,
      inside the cell, RNA egress completes in about 2 min. This suggests the existence
      of cellular uncoating facilitators.

PMID- 24672024
TI  - Animal model of respiratory syncytial virus: CD8+ T cells cause a cytokine storm
      that is chemically tractable by sphingosine-1-phosphate 1 receptor agonist
      therapy.
AB  - The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory
      response driven by cytokine and immune cell components. The cytokine storm during
      influenza virus infection, whereby the amplified innate immune response is
      primarily responsible for pulmonary damage, has been well characterized. Now we
      describe a novel event where virus-specific T cells induce a cytokine storm. The
      paramyxovirus pneumonia virus of mice (PVM) is a model of human respiratory
      syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were infected with PVM,
      the innate inflammatory response was undetectable until day 5 postinfection, at
      which time CD8(+) T cells infiltrated into the lung, initiating a cytokine storm
      by their production of gamma interferon (IFN-gamma) and tumor necrosis factor
      alpha (TNF-alpha). Administration of an immunomodulatory sphingosine-1-phosphate
      (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine
      storm by blunting the PVM-specific CD8(+) T cell response, resulting in
      diminished pulmonary disease and enhanced survival. IMPORTANCE: A dysregulated
      overly exuberant immune response, termed a "cytokine storm," accompanies virus
      induced acute respiratory diseases (VARV), is primarily responsible for the
      accompanying high morbidity and mortality, and can be controlled therapeutically
      in influenza virus infection of mice and ferrets by administration of sphingosine
      1-phosphate 1 receptor (S1P1R) agonists. Here, two novel findings are recorded.
      First, in contrast to influenza infection, where the cytokine storm is initiated
      early by the innate immune system, for pneumonia virus of mice (PVM), a model of
      RSV, the cytokine storm is initiated late in infection by the adaptive immune
      response: specifically, by virus-specific CD8 T cells via their release of IFN
      gamma and TNF-alpha. Blockading these cytokines with neutralizing antibodies
      blunts the cytokine storm and protects the host. Second, PVM infection is
      controlled by administration of an S1P1R agonist.

PMID- 24672025
TI  - NTPDASE4 gene products cooperate with the adenovirus E4orf4 protein through PP2A
      dependent and -independent mechanisms and contribute to induction of cell death.
AB  - The adenovirus E4orf4 protein induces nonclassical apoptosis in mammalian cells
      through at least two complementing pathways regulated by the interactions of
      E4orf4 with protein phosphatase 2A (PP2A) and Src kinases. In Saccharomyces
      cerevisiae cells, which do not express Src, E4orf4 induces PP2A-dependent
      toxicity. The yeast Golgi apyrase Ynd1 was found to contribute to E4orf4-mediated
      toxicity and to interact with the PP2A-B55alpha regulatory subunit. In addition,
      a mammalian Ynd1 orthologue, the NTPDASE4 gene product Golgi UDPase, was shown to
      physically interact with E4orf4. Here we report that knockdown of NTPDASE4
      suppressed E4orf4-induced cell death. Conversely, overexpression of the NTPDASE4
      gene products Golgi UDPase and LALP70 enhanced E4orf4-induced cell killing. We
      found that similarly to results obtained in yeast, the apyrase activity of
      mammalian UDPase was not required for its contribution to E4orf4-induced
      toxicity. The interaction between E4orf4 and UDPase had two consequences: a PP2A
      dependent one, resulting in increased UDPase levels, and a PP2A-independent
      outcome that led to dissociation of large UDPase-containing protein complexes.
      The present report extends our findings in yeast to E4orf4-mediated death of
      mammalian cells, and combined with previous results, it suggests that the E4orf4
      NTPDase4 pathway, partly in association with PP2A, may provide an alternative
      mechanism for the E4orf4-Src pathway to contribute to the cytoplasmic death
      function of E4orf4. IMPORTANCE: The adenovirus E4orf4 protein contributes to
      regulation of the progression of virus infection from the early to the late
      phase, and when expressed alone, it induces a unique caspase-independent
      programmed cell death which is more efficient in cancer cells than in normal
      cells. The interactions of E4orf4 with cellular proteins that mediate its
      functions, such as PP2A and Src kinases, are highly conserved in evolution. The
      results presented here reveal that the NTPDASE4 gene product Golgi UDPase, first
      discovered to contribute to E4orf4 toxicity in Saccharomyces cerevisiae,
      associates with E4orf4 and plays a role in induction of cell death in mammalian
      cells. Details of the functional interaction between E4orf4, PP2A, and the UDPase
      are described. Identification of the evolutionarily conserved mechanisms
      underlying E4orf4 activity will increase our understanding of the interactions
      between the virus and the host cell and will contribute to our grasp of the
      unique mode of E4orf4-induced cell death.

PMID- 24672026
TI  - High level of vector competence of Aedes aegypti and Aedes albopictus from ten
      American countries as a crucial factor in the spread of Chikungunya virus.
AB  - Chikungunya virus (CHIKV) causes a major public health problem. In 2004, CHIKV
      began an unprecedented global expansion and has been responsible for epidemics in
      Africa, Asia, islands in the Indian Ocean region, and surprisingly, in temperate
      regions, such as Europe. Intriguingly, no local transmission of chikungunya virus
      (CHIKV) had been reported in the Americas until recently, despite the presence of
      vectors and annually reported imported cases. Here, we assessed the vector
      competence of 35 American Aedes aegypti and Aedes albopictus mosquito populations
      for three CHIKV genotypes. We also compared the number of viral particles of
      different CHIKV strains in mosquito saliva at two different times postinfection.
      Primarily, viral dissemination rates were high for all mosquito populations
      irrespective of the tested CHIKV isolate. In contrast, differences in
      transmission efficiency (TE) were underlined in populations of both species
      through the Americas, suggesting the role of salivary glands in selecting CHIKV
      for highly efficient transmission. Nonetheless, both mosquito species were
      capable of transmitting all three CHIKV genotypes, and TE reached alarming rates
      as high as 83.3% and 96.7% in A. aegypti and A. albopictus populations,
      respectively. A. albopictus better transmitted the epidemic mutant strain
      CHIKV_0621 of the East-Central-South African (ECSA) genotype than did A. aegypti,
      whereas the latter species was more capable of transmitting the original ECSA
      CHIKV_115 strain and also the Asian genotype CHIKV_NC. Therefore, a high risk of
      establishment and spread of CHIKV throughout the tropical, subtropical, and even
      temperate regions of the Americas is more real than ever. IMPORTANCE: Until
      recently, the Americas had never reported chikungunya (CHIK) autochthonous
      transmission despite its global expansion beginning in 2004. Large regions of the
      continent are highly infested with Aedes aegypti and Aedes albopictus mosquitoes,
      and millions of dengue (DEN) cases are annually recorded. Indeed, DEN virus and
      CHIK virus (CHIKV) share the same vectors. Due to a recent CHIK outbreak
      affecting Caribbean islands, the need for a Pan-American evaluation of vector
      competence was compelling as a key parameter in assessing the epidemic risk. We
      demonstrated for the first time that A. aegypti and A. albopictus populations
      throughout the continent are highly competent to transmit CHIK irrespective of
      the viral genotypes tested. The risk of CHIK spreading throughout the tropical,
      subtropical, and even temperate regions of the Americas is more than ever a
      reality. In light of our results, local authorities should immediately pursue and
      reinforce epidemiological and entomological surveillance to avoid a severe
      epidemic.

PMID- 24672027
TI  - Lysophosphatidylcholine reversibly arrests pore expansion during syncytium
      formation mediated by diverse viral fusogens.
AB  - Using lysophosphatidylcholine, a curvature-inducing lysolipid, we have isolated a
      reversible, "stalled pore" phenotype during syncytium formation induced by the
      p14 fusion-associated small transmembrane (FAST) protein and influenza virus
      hemagglutinin (HA) fusogens. This is the first evidence that lateral propagation
      of stable fusion pores leading to syncytiogenesis mediated by diverse viral
      fusogens is inhibited by promotion of positive membrane curvature in the outer
      leaflets of the lipid bilayer surrounding intercellular fusion pores. 

PMID- 24672028
TI  - Activation of Kaposi's sarcoma-associated herpesvirus (KSHV) by inhibitors of
      class III histone deacetylases: identification of sirtuin 1 as a regulator of the
      KSHV life cycle.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) establishes persistent latent
      infection in immunocompetent hosts. Disruption of KSHV latency results in viral
      lytic replication, which promotes the development of KSHV-related malignancies in
      immunocompromised individuals. While inhibitors of classes I and II histone
      deacetylases (HDACs) potently reactivate KSHV from latency, the role of class III
      HDAC sirtuins (SIRTs) in KSHV latency remains unclear. Here, we examined the
      effects of inhibitors of SIRTs, nicotinamide (NAM) and sirtinol, on KSHV
      reactivation from latency. Treatment of latently KSHV-infected cells with NAM or
      sirtinol induced transcripts and proteins of the master lytic transactivator RTA
      (ORF50), early lytic genes ORF57 and ORF59, and late lytic gene ORF65 and
      increased the production of infectious virions. NAM increased the acetylation of
      histones H3 and H4 as well as the level of the active histone H3 trimethyl Lys4
      (H3K4me3) mark but decreased the level of the repressive histone H3 trimethyl
      Lys27 (H3K27me3) mark in the RTA promoter. Consistent with these results, we
      detected SIRT1 binding to the RTA promoter. Importantly, knockdown of SIRT1 was
      sufficient to increase the expression of KSHV lytic genes. Accordingly, the level
      of the H3K4me3 mark in the RTA promoter was increased following SIRT1 knockdown,
      while that of the H3K27me3 mark was decreased. Furthermore, SIRT1 interacted with
      RTA and inhibited RTA transactivation of its own promoter and that of its
      downstream target, the viral interleukin-6 gene. These results indicate that
      SIRT1 regulates KSHV latency by inhibiting different stages of viral lytic
      replication and link the cellular metabolic state with the KSHV life cycle.
      IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causal agent of
      several malignancies, including Kaposi's sarcoma, commonly found in
      immunocompromised patients. While latent infection is required for the
      development of KSHV-induced malignancies, viral lytic replication also promotes
      disease progression. However, the mechanism controlling KSHV latent versus lytic
      replication remains unclear. In this study, we found that class III histone
      deacetylases (HDACs), also known as SIRTs, whose activities are linked to the
      cellular metabolic state, mediate KSHV replication. Inhibitors of SIRTs can
      reactivate KSHV from latency. SIRTs mediate KSHV latency by epigenetically
      silencing a key KSHV lytic replication activator, RTA. We found that one of the
      SIRTs, SIRT1, binds to the RTA promoter to mediate KSHV latency. Knockdown of
      SIRT1 is sufficient to induce epigenetic remodeling and KSHV lytic replication.
      SIRT1 also interacts with RTA and inhibits RTA's transactivation function,
      preventing the expression of its downstream genes. Our results indicate that
      SIRTs regulate KSHV latency by inhibiting different stages of viral lytic
      replication and link the cellular metabolic state with the KSHV life cycle.

PMID- 24672029
TI  - NEMO is essential for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13
      induced gene expression and protection against death receptor-induced cell death,
      and its N-terminal 251 residues are sufficient for this process.
AB  - Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein
      (vFLIP) K13 was originally believed to protect virally infected cells against
      death receptor-induced apoptosis by interfering with caspase 8/FLICE activation.
      Subsequent studies revealed that K13 also activates the NF-kappaB pathway by
      binding to the NEMO/inhibitor of NF-kappaB (IkappaB) kinase gamma (IKKgamma)
      subunit of an IKK complex and uses this pathway to modulate the expression of
      genes involved in cellular survival, proliferation, and the inflammatory
      response. However, it is not clear if K13 can also induce gene expression
      independently of NEMO/IKKgamma. The minimum region of NEMO that is sufficient for
      supporting K13-induced NF-kappaB has not been delineated. Furthermore, the
      contribution of NEMO and NF-kappaB to the protective effect of K13 against death
      receptor-induced apoptosis remains to be determined. In this study, we used
      microarray analysis on K13-expressing wild-type and NEMO-deficient cells to
      demonstrate that NEMO is required for modulation of K13-induced genes.
      Reconstitution of NEMO-null cells revealed that the N-terminal 251 amino acid
      residues of NEMO are sufficient for supporting K13-induced NF-kappaB but fail to
      support tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB. K13 failed to
      protect NEMO-null cells against TNF-alpha-induced cell death but protected those
      reconstituted with the NEMO mutant truncated to include only the N-terminal 251
      amino acid residues [the NEMO(1-251) mutant]. Taken collectively, our results
      demonstrate that NEMO is required for modulation of K13-induced genes and the N
      terminal 251 amino acids of NEMO are sufficient for supporting K13-induced NF
      kappaB. Finally, the ability of K13 to protect against TNF-alpha-induced cell
      death is critically dependent on its ability to interact with NEMO and activate
      NF-kappaB. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13
      is believed to protect virally infected cells against death receptor-induced
      apoptosis and to activate the NF-kappaB pathway by binding to adaptor protein
      NEMO/IKKgamma. However, whether K13 can also induce gene expression independently
      of NEMO and the minimum region of NEMO that is sufficient for supporting K13
      induced NF-kappaB remain to be delineated. Furthermore, the contribution of NEMO
      and NF-kappaB to the protective effect of K13 against death receptor-induced
      apoptosis is not clear. We demonstrate that NEMO is required for modulation of
      K13-induced genes and its N-terminal 251 amino acids are sufficient for
      supporting K13-induced NF-kappaB. The ability of K13 to protect against TNF-alpha
      induced cell death is critically dependent on its ability to interact with NEMO
      and activate NF-kappaB. Our results suggest that K13-based gene therapy
      approaches may have utility for the treatment of patients with NEMO mutations and
      immunodeficiency.

PMID- 24672030
TI  - A unique N-terminal sequence in the Carnation Italian ringspot virus p36
      replicase-associated protein interacts with the host cell ESCRT-I component
      Vps23.
AB  - Like most positive-strand RNA viruses, infection by plant tombusviruses results
      in extensive rearrangement of specific host cell organelle membranes that serve
      as the sites of viral replication. The tombusvirus Tomato bushy stunt virus
      (TBSV) replicates within spherules derived from the peroxisomal boundary
      membrane, a process that involves the coordinated action of various viral and
      cellular factors, including constituents of the endosomal sorting complex
      required for transport (ESCRT). ESCRT is comprised of a series of protein
      subcomplexes (i.e., ESCRT-0 -I, -II, and -III) that normally participate in late
      endosome biogenesis and some of which are also hijacked by certain enveloped
      retroviruses (e.g., HIV) for viral budding from the plasma membrane. Here we show
      that the replication of Carnation Italian ringspot virus (CIRV), a tombusvirus
      that replicates at mitochondrial membranes also relies on ESCRT. In plant cells,
      CIRV recruits the ESCRT-I protein, Vps23, to mitochondria through an interaction
      that involves a unique region in the N terminus of the p36 replicase-associated
      protein that is not conserved in TBSV or other peroxisome-targeted tombusviruses.
      The interaction between p36 and Vps23 also involves the Vps23 C-terminal
      steadiness box domain and not its N-terminal ubiquitin E2 variant domain, which
      in the case of TBSV (and enveloped retroviruses) mediates the interaction with
      ESCRT. Overall, these results provide evidence that CIRV uses a unique N-terminal
      sequence for the recruitment of Vps23 that is distinct from those used by TBSV
      and certain mammalian viruses for ESCRT recruitment. Characterization of this
      novel interaction with Vps23 contributes to our understanding of how CIRV may
      have evolved to exploit key differences in the plant ESCRT machinery. IMPORTANCE:
      Positive-strand RNA viruses replicate their genomes in association with specific
      host cell membranes. To accomplish this, cellular components responsible for
      membrane biogenesis and modeling are appropriated by viral proteins and
      redirected to assemble membrane-bound viral replicase complexes. The diverse
      pathways leading to the formation of these replication structures are poorly
      understood. We have determined that the cellular ESCRT system that is normally
      responsible for mediating late endosome biogenesis is also involved in the
      replication of the tombusvirus Carnation Italian ringspot virus (CIRV) at
      mitochondria. Notably, CIRV recruits ESCRT to the mitochondrial outer membrane
      via an interaction between a unique motif in the viral protein p36 and the ESCRT
      component Vps23. Our findings provide new insights into tombusvirus replication
      and the virus-induced remodeling of plant intracellular membranes, as well as
      normal ESCRT assembly in plants.

PMID- 24672031
TI  - Human metapneumovirus virus-like particles induce protective B and T cell
      responses in a mouse model.
AB  - Human metapneumovirus (HMPV) is a leading cause of respiratory disease in
      infants, children, and the elderly worldwide, yet no licensed vaccines exist.
      Live-attenuated vaccines present safety challenges, and protein subunit vaccines
      induce primarily antibody responses. Virus-like particles (VLPs) are an
      attractive alternative vaccine approach because of reduced safety concerns
      compared with live vaccines. We generated HMPV VLPs by expressing viral proteins
      in suspension-adapted human embryonic kidney epithelial (293-F) cells and found
      that the viral matrix (M) and fusion (F) proteins were sufficient to form VLPs.
      We previously reported that the VLPs resemble virus morphology and incorporate
      fusion-competent F protein (R. G. Cox, S. B. Livesay, M. Johnson, M. D. Ohi, and
      J. V. Williams, J. Virol. 86:12148-12160, 2012), which we hypothesized would
      elicit F-specific antibody and T cell responses. In this study, we tested whether
      VLP immunization could induce protective immunity to HMPV by using a mouse model.
      C57BL/6 mice were injected twice intraperitoneally with VLPs alone or with
      adjuvant and subsequently challenged with HMPV. Mice were euthanized 5 days
      postinfection, and virus titers, levels of neutralizing antibodies, and numbers
      of CD3(+) T cells were quantified. Mice immunized with VLPs mounted an F-specific
      antibody response and generated CD8(+) T cells recognizing an F protein-derived
      epitope. VLP immunization induced a neutralizing-antibody response that was
      enhanced by the addition of either TiterMax Gold or alpha-galactosylceramide
      adjuvant, though adjuvant reduced cellular immune responses. Two doses of VLPs
      conferred complete protection from HMPV replication in the lungs of mice and were
      not associated with a Th2-skewed cytokine response. These results suggest that
      nonreplicating VLPs are a promising vaccine candidate for HMPV. IMPORTANCE: Human
      metapneumovirus (HMPV) is a leading cause of acute respiratory infection in
      infants, children, and the elderly worldwide, yet no licensed vaccines exist.
      Live-attenuated vaccines present safety challenges, and protein subunit vaccines
      induce primarily antibody responses. Virus-like particles (VLPs) are an
      attractive alternative vaccine approach. We generated HMPV VLPs by expressing the
      viral matrix (M) and fusion (F) proteins in mammalian cells. We found that mice
      immunized with VLPs mounted an F-specific antibody response and generated CD8(+)
      T cells recognizing an F protein-derived epitope. VLP immunization induced a
      neutralizing-antibody response that was enhanced by the addition of either
      TiterMax Gold or alpha-galactosylceramide adjuvant. Two doses of VLPs conferred
      complete protection against HMPV replication in the lungs of mice and were not
      associated with a Th2-skewed cytokine response. These results suggest that
      nonreplicating VLPs are a promising vaccine candidate for HMPV.

PMID- 24672032
TI  - Reduction of microRNA 122 expression in IFNL3 CT/TT carriers and during
      progression of fibrosis in patients with chronic hepatitis C.
AB  - The microRNA miR-122 is highly expressed in the liver and stimulates hepatitis C
      virus (HCV) replication in vitro. IFNL3 (lambda-3 interferon gene) polymorphisms
      and the expression of miR-122 have been associated with sustained virological
      response (SVR) to treatment with pegylated interferon plus ribavirin in patients
      with chronic hepatitis C (CHC). We investigated, in vivo, the relationship
      between miR-122 expression, IFNL3 polymorphism, fibrosis, and response to PEG-IFN
      plus ribavirin. Pretreatment liver biopsy specimens and serum samples from 133
      patients with CHC were included. Sixty-six patients achieved SVR, and 64 failed
      to respond to the treatment (43 nonresponders [NR] and 21 relapsers [RR]). All
      stages of fibrosis were represented, with 39, 50, 23, and 19 patients,
      respectively, having Metavir scores of F1, F2, F3, and F4. miR-122 expression was
      assessed by real-time quantitative PCR (RT-qPCR) and IFNL3 rs12979860 by direct
      sequencing. Hepatic miR-122 expression was higher in patients with the IFNL3 CC
      genotype than in those with the IFNL3 CT or TT genotype, in all patients (P =
      0.025), and in NRs plus RRs (P = 0.013). Increased hepatic miR-122 was more
      strongly associated with complete early virological response (cEVR) (P = 0.003)
      than with SVR (P = 0.016). In multivariate analysis, increased hepatic miR-122
      was only associated with the IFNL3 CC genotype. miR-122 was decreased in patients
      with advanced fibrosis (Metavir scores of F3 and F4) compared to its levels in
      patients with mild and moderate fibrosis (F1 and F2) (P = 0.01). Serum and
      hepatic expression of miR-122 were not associated. The association between miR
      122 and IFNL3 was stronger than the association between miR-122 and response to
      treatment. miR-122 may play a role in the early viral decline that is dependent
      on IFNL3 and the innate immune response. IMPORTANCE: miR-122 plays a crucial role
      during HCV infection. Moreover, it was reported that miR-122 binding within the
      HCV genome stimulates its replication. Moreover, miR-122 is highly expressed
      within hepatocytes, where it regulates many cellular pathways. A reduction of miR
      122 expression has been suggested to be associated with responsiveness to IFN
      based therapy in patients with chronic hepatitis C. Several independent genome
      wide association studies reported a strong association between IFNL3 polymorphism
      and responsiveness to IFN-based therapy. We report here a strong association
      between the expression of miR-122 and IFNL3 polymorphism that is independent of
      the response to the treatment. Our data suggest that modification of miR-122
      expression may play an important role in the molecular mechanism associated with
      IFNL3 polymorphism. Moreover, we report a reduction of miR-122 at more advanced
      stages of fibrosis in patients with chronic hepatitis C.

PMID- 24672033
TI  - Intestinal epithelial barrier disruption through altered mucosal microRNA
      expression in human immunodeficiency virus and simian immunodeficiency virus
      infections.
AB  - Epithelial barrier dysfunction during human immunodeficiency virus (HIV)
      infection has largely been attributed to the rapid and severe depletion of CD4(+)
      T cells in the gastrointestinal (GI) tract. Although it is known that changes in
      mucosal gene expression contribute to intestinal enteropathy, the role of small
      noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using
      the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV
      pathogenesis, we investigated the effect of viral infection on miRNA expression
      in intestinal mucosa. SIV infection led to a striking decrease in the expression
      of mucosal miRNA compared to that in uninfected controls. This decrease coincided
      with an increase in 5'-3'-exoribonuclease 2 protein and alterations in DICER1 and
      Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways
      involved in epithelial proliferation, differentiation, and immune response.
      Decreased expression of several miRNA involved in maintaining epithelial
      homeostasis in the gut was localized to the proliferative crypt region of the
      intestinal epithelium. Our findings suggest that SIV-induced decreased expression
      of miRNA involved in epithelial homeostasis, disrupted expression of miRNA
      biogenesis machinery, and increased expression of XRN2 are involved in the
      development of epithelial barrier dysfunction and gastroenteropathy. IMPORTANCE:
      MicroRNA (miRNA) regulate the development and function of intestinal epithelial
      cells, and many viruses disrupt normal host miRNA expression. In this study, we
      demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine
      during infection. The depletion of several key miRNA is localized to the
      proliferative crypt region of the gut epithelium. These miRNA are known to
      control expression of genes involved in inflammation, cell death, and epithelial
      maturation. Our data indicate that this disruption might be caused by altered
      expression of miRNA biogenesis machinery during infection. These findings suggest
      that the disruption of miRNA in the small intestine likely plays a role in
      intestinal enteropathy during HIV infection.

PMID- 24672034
TI  - The Thr205 phosphorylation site within respiratory syncytial virus matrix (M)
      protein modulates M oligomerization and virus production.
AB  - Human respiratory syncytial virus (RSV) is the most common cause of bronchiolitis
      and pneumonia in infants and the elderly worldwide; however, there is no licensed
      RSV vaccine or effective drug treatment available. The RSV matrix (M) protein
      plays key roles in virus assembly and budding, but the protein interactions that
      govern budding of infectious virus are not known. In this study, we focus on M
      protein and identify a key phosphorylation site (Thr205) in M that is critical
      for RSV infectious virus production. Recombinant virus with a nonphosphorylatable
      alanine (Ala) residue at the site was markedly attenuated, whereas virus with a
      phosphomimetic aspartate (Asp) resulted in a nonviable virus which could only be
      recovered with an additional mutation in M (serine to asparagine at position
      220), strongly implying that Thr205 is critical for viral infectivity.
      Experiments in vitro showed that mutation of Thr205 does not affect M stability
      or the ability to form dimers but implicate an effect on higher-order oligomer
      assembly. In transfected and infected cells, Asp substitution of Thr205 appeared
      to impair M oligomerization; typical filamentous structures still formed at the
      plasma membrane, but M assembly during the ensuing elongation process seemed to
      be impaired, resulting in shorter and more branched filaments as observed using
      electron microscopy (EM). Our data thus imply for the first time that M
      oligomerization, regulated by a negative charge at Thr205, may be critical to
      production of infectious RSV. IMPORTANCE: We show here for the first time that
      RSV M's role in virus assembly/release is strongly dependent on threonine 205
      (Thr205), a consensus site for CK2, which appears to play a key regulatory role
      in modulating M oligomerization and association with virus filaments. Our
      analysis indicates that T205 mutations do not impair M dimerization or viruslike
      filament formation per se but rather the ability of M to assemble in ordered
      fashion on the viral filaments themselves. This appears to impact in turn upon
      the infectivity of released virus rather than on virus production or release
      itself. Thus, M oligomerization would appear to be a target of interest for the
      development of anti-RSV agents; further, the recombinant T205-substituted mutant
      viruses described here would appear to be the first RSV mutants affected in viral
      maturation to our knowledge and hence of considerable interest for vaccine
      approaches in the future.

PMID- 24672035
TI  - Nuclear magnetic resonance structure revealed that the human polyomavirus JC
      virus agnoprotein contains an alpha-helix encompassing the Leu/Ile/Phe-rich
      domain.
AB  - Agnoprotein is a small multifunctional regulatory protein required for sustaining
      the productive replication of JC virus (JCV). It is a mostly cytoplasmic protein
      localizing in the perinuclear area and forms highly stable dimers/oligomers
      through a Leu/Ile/Phe-rich domain. There have been no three-dimensional
      structural data available for agnoprotein due to difficulties associated with the
      dynamic conversion from monomers to oligomers. Here, we report the first nuclear
      magnetic resonance (NMR) structure of a synthetic agnoprotein peptide spanning
      amino acids Thr17 to Glu55 where Lys23 to Phe39 encompassing the Leu/Ile/Phe-rich
      domain forms an amphipathic alpha-helix. On the basis of these structural data, a
      number of Ala substitution mutations were made to investigate the role of the
      alpha-helix in the structure and function of agnoprotein. Single L29A and L36A
      mutations exhibited a significant negative effect on both protein stability and
      viral replication, whereas the L32A mutation did not. In addition, the L29A
      mutant displayed a highly nuclear localization pattern, in contrast to the
      pattern for the wild type (WT). Interestingly, a triple mutant, the
      L29A+L32A+L36A mutant, yielded no detectable agnoprotein expression, and the
      replication of this JCV mutant was significantly reduced, suggesting that Leu29
      and Leu36 are located at the dimer interface, contributing to the structure and
      stability of agnoprotein. Two other single mutations, L33A and E34A, did not
      perturb agnoprotein stability as drastically as that observed with the L29A and
      L36A mutations, but they negatively affected viral replication, suggesting that
      the role of these residues is functional rather than structural. Thus, the
      agnoprotein dimerization domain can be targeted for the development of novel
      drugs active against JCV infection. IMPORTANCE: Agnoprotein is a small regulatory
      protein of JC virus (JCV) and is required for the successful completion of the
      viral replication cycle. It forms highly stable dimers and oligomers through its
      hydrophobic (Leu/Ile/Phe-rich) domain, which has been shown to play essential
      roles in the stability and function of the protein. In this work, the Leu/Ile/Phe
      rich domain has been further characterized by NMR studies using an agnoprotein
      peptide spanning amino acids T17 to Q54. Those studies revealed that the
      dimerization domain of the protein forms an amphipathic alpha-helix. Subsequent
      NMR structure-based mutational analysis of the region highlighted the critical
      importance of certain amino acids within the alpha-helix for the stability and
      function of agnoprotein. In conclusion, this study provides a solid foundation
      for developing effective therapeutic approaches against the dimerization domain
      of the protein to inhibit its critical roles in JCV infection.

PMID- 24672036
TI  - Cryo-electron microscopy study of insect cell-expressed enterovirus 71 and
      coxsackievirus a16 virus-like particles provides a structural basis for vaccine
      development.
AB  - Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two most common
      etiological agents responsible for the epidemics of hand, foot, and mouth disease
      (HFMD), a childhood illness with occasional severe neurological complications. A
      number of vaccine candidates against EV71 or CA16 have been reported; however, no
      vaccine is currently available for clinical use. Here, we generated a secreted
      version of EV71 and CA16 virus-like particles (VLPs) using a baculovirus-insect
      cell expression system and reconstructed the three-dimensional (3D) structures of
      both VLPs by cryo-electron microscopy (cryo-EM) single-particle analysis at 5.2-A
      and 5.5-A resolutions, respectively. The reconstruction results showed that the
      cryo-EM structures of EV71 and CA16 VLPs highly resemble the recently published
      crystal structures for EV71 natural empty particles and CA16 135S-like expanded
      particles, respectively. Our cryo-EM analysis also revealed that the majority of
      previously identified linear neutralizing epitopes are well preserved on the
      surface of EV71 and CA16 VLPs. In addition, both VLPs were able to induce
      efficiently neutralizing antibodies against various strains of EV71 and CA16
      viruses in mouse immunization. These studies provide a structural basis for the
      development of insect cell-expressed VLP vaccines and for a potential bivalent
      VLP vaccine against both EV71- and CA16-associated HFMD. IMPORTANCE: The recent
      outbreaks of hand, foot, and mouth disease (HFMD) in the Asia Pacific region
      spurred the search for effective vaccines against EV71 and CA16 viruses, the two
      most common etiological agents responsible for HFMD. In this paper, we show that
      secreted versions of EV71 and CA16 VLPs generated in the baculovirus-insect cell
      expression system highly resemble the crystal structures of their viral
      conterparts and that the majority of previously identified linear neutralizing
      epitopes are well preserved on the VLP surfaces. In addition, the generated VLPs
      can efficiently induce neutralizing antibodies against various strains of EV71
      and CA16 viruses in mouse immunization. These studies provide a structural basis
      for the development of insect cell-expressed VLP vaccines and for a potential
      bivalent VLP vaccine against both EV71- and CA16-associated HFMD.

PMID- 24672037
TI  - Substitution of herpes simplex virus 1 entry glycoproteins with those of
      saimiriine herpesvirus 1 reveals a gD-gH/gL functional interaction and a region
      within the gD profusion domain that is critical for fusion.
AB  - To gain insight into the mechanism of herpesvirus entry into cells, the four
      glycoproteins that are necessary for herpes simplex virus (HSV) fusion were
      cloned from the saimiriine herpesvirus 1 (SaHV-1) genome, a primate member of the
      alphaherpesvirus family. Cell-cell fusion assays indicate that SaHV-1 entry
      glycoproteins function with the previously identified alphaherpesvirus entry
      receptors nectin-1 and CD155 but not with herpesvirus entry mediator (HVEM) or
      paired immunoglobulin-like type 2 receptor alpha (PILRalpha). Replacement of HSV
      1 gD with the SaHV-1 gD homolog resulted in a complete loss of fusion function
      when coexpressed with HSV-1 gB and gH/gL. HSV-1 gD was also unable to substitute
      for SaHV-1 gD when coexpressed with SaHV-1 gB and gH/gL. Similarly, the gH/gL
      heterodimers from HSV-1 and SaHV-1 were not interchangeable. In contrast, both
      the HSV-1 and SaHV-1 gB homologs retained function in a heterotypic context.
      These results suggest that an essential interaction between homotypic gD and
      gH/gL occurs during both HSV-1 and SaHV-1 entry. To map the site of this
      homotypic interaction, we created a series of gD chimeras, focusing on the
      "profusion domain" (PFD) that consists of HSV-1 gD residues 261 to 305 or SaHV-1
      gD residues 264 to 307. We identified a seven-amino-acid stretch (264 RTLPPPK
      270) at the N terminus of the SaHV-1 gD PFD that contributes to homotypic fusion.
      Finally, we found that the gD receptor-binding region and PFD cannot function
      independently but that both can inhibit the function of wild-type gD. IMPORTANCE:
      The herpesvirus entry machinery requires the concerted action of at least four
      glycoproteins; however, details of the interactions among these glycoproteins are
      not well understood. Like HSV-1, SaHV-1 belongs to the alphaherpesvirus
      subfamily. Using cell-cell fusion experiments, we found that SaHV-1 uses the
      entry receptors nectin-1 and CD155 but not HVEM or PILRalpha. By swapping the
      entry glycoproteins between HSV-1 and SaHV-1, we revealed a functional
      interaction between gD and gH/gL. To examine the homotypic interaction site on
      gD, we evaluated the function of a panel of HSV-1/SaHV-1 gD chimeras and
      identified a small region in the SaHV-1 gD profusion domain that is critical for
      SaHV-1 fusion. This study contributes to our understanding of the molecular
      mechanisms of herpesvirus entry and membrane fusion.

PMID- 24672038
TI  - Human metapneumovirus SH and G glycoproteins inhibit macropinocytosis-mediated
      entry into human dendritic cells and reduce CD4+ T cell activation.
AB  - Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease
      worldwide. HMPV reinfections are common in healthy adults and children,
      suggesting that the protective immune response to HMPV is incomplete and short
      lived. We used gene-deletion viruses to evaluate the role of the attachment G and
      small hydrophobic SH glycoproteins on virus uptake by primary human monocyte
      derived dendritic cells (MDDC) in vitro and on subsequent MDDC maturation and
      activation of autologous T cells. HMPV with deletion of G and SH (DeltaSHG)
      exhibited increased infectivity but had little effect on MDDC maturation.
      However, MDDC stimulated with DeltaSHG induced increased proliferation of
      autologous Th1-polarized CD4(+) T cells. This effect was independent of virus
      replication. Increased T cell proliferation was strictly dependent on contact
      between virus-stimulated MDDC and CD4(+) T cells. Confocal microscopy revealed
      that deletion of SH and G was associated with an increased number of
      immunological synapses between memory CD4(+) T cells and virus-stimulated MDDC.
      Uptake of HMPV by MDDC was found to be primarily by macropinocytosis. Uptake of
      wild-type (WT) virus was reduced compared to that of DeltaSHG, indicative of
      inhibition by the SH and G glycoproteins. In addition, DC-SIGN-mediated
      endocytosis provided a minor alternative pathway that depended on SH and/or G and
      thus operated only for WT. Altogether, our results show that SH and G
      glycoproteins reduce the ability of HMPV to be internalized by MDDC, resulting in
      a reduced ability of the HMPV-stimulated MDDC to activate CD4(+) T cells. This
      study describes a previously unknown mechanism of virus immune evasion.
      IMPORTANCE: Human metapneumovirus (HMPV) is a major etiologic agent of
      respiratory disease worldwide. HMPV reinfections are common in healthy adults and
      children, suggesting that the protective immune response to HMPV is incomplete
      and short-lived. We found that HMPV attachment G and small hydrophobic SH
      glycoproteins reduce the ability of HMPV to be internalized by macropinocytosis
      into human dendritic cells (DC). This results in a reduced ability of the HMPV
      stimulated DC to activate Th1-polarized CD4(+) T cells. These results contribute
      to a better understanding of the nature of incomplete protection against this
      important human respiratory virus, provide new information on the entry of HMPV
      into human cells, and describe a new mechanism of virus immune evasion.

PMID- 24672039
TI  - Comparative complete genome analysis of chicken and Turkey megriviruses (family
      picornaviridae): long 3' untranslated regions with a potential second open
      reading frame and evidence for possible recombination.
AB  - Members of the family Picornaviridae consist of small positive-sense single
      stranded RNA (+ssRNA) viruses capable of infecting various vertebrate species,
      including birds. One of the recently identified avian picornaviruses, with a
      remarkably long (>9,040-nucleotide) but still incompletely sequenced genome, is
      turkey hepatitis virus 1 (THV-1; species Melegrivirus A, genus Megrivirus), a
      virus associated with liver necrosis and enteritis in commercial turkeys
      (Meleagris gallopavo). This report presents the results of the genetic analysis
      of three complete genomes of megriviruses from fecal samples of chickens
      (chicken/B21-CHV/2012/HUN, GenBank accession no. KF961186, and chicken/CHK-IV
      CHV/2013/HUN, GenBank accession no. KF961187) (Gallus gallus domesticus) and
      turkey (turkey/B407-THV/2011/HUN, GenBank accession no. KF961188) (Meleagris
      gallopavo) with the largest picornavirus genome (up to 9,739 nucleotides) so far
      described. The close phylogenetic relationship to THV-1 in the nonstructural
      protein-coding genome region and possession of the same internal ribosomal entry
      site type (IVB-like) suggest that the study strains belong to the genus
      Megrivirus. However, the genome comparisons revealed numerous unique variations
      (e.g., different numbers of potential 2A peptides, unusually long 3' genome parts
      with various lengths of a potential second open reading frame, and multiple
      repeating sequence motifs in the 3' untranslated region) and heterogeneous
      sequence relationships between the structural and nonstructural genome regions.
      These differences suggest the classification of chicken megrivirus-like viruses
      into a candidate novel species in the genus Megrivirus. Based on the different
      phylogenetic positions of chicken megrivirus-like viruses at the structural and
      nonstructural genome regions, the recombinant nature of these viruses is
      plausible. IMPORTANCE: The comparative genome analysis of turkey and novel
      chicken megriviruses revealed numerous unique genome features, e.g., up to four
      potential 2A peptides, unusually long 3' genome parts with various lengths
      containing a potential second open reading frame, multiple repeating sequence
      motifs, and heterogeneous sequence relationships (possibly due to a recombination
      event) between the structural and nonstructural genome regions. Our results could
      help us to better understand the evolution and diversity (in terms of sequence
      and genome layout) of picornaviruses.

PMID- 24672040
TI  - An allometric relationship between the genome length and virion volume of
      viruses.
AB  - Virions vary in size by at least 4 orders of magnitude, yet the evolutionary
      forces responsible for this enormous diversity are unknown. We document a
      significant allometric relationship, with an exponent of approximately 1.5,
      between the genome length and virion volume of viruses and find that this
      relationship is not due to geometric constraints. Notably, this allometric
      relationship holds regardless of genomic nucleic acid, genome structure, or type
      of virion architecture and therefore represents a powerful scaling law. In
      contrast, no such relationship is observed at the scale of individual genes.
      Similarly, after adjusting for genome length, no association is observed between
      virion volume and the number of proteins, ruling out protein number as the
      explanation for the relationship between genome and virion sizes. Such a
      fundamental allometric relationship not only sheds light on the constraints to
      virus evolution, in that increases in virion size but not necessarily structure
      are associated with concomitant increases in genome size, but also implies that
      virion sizes in nature can be broadly predicted from genome sequence data alone.
      IMPORTANCE: Viruses vary dramatically in both genome and virion sizes, but the
      factors responsible for this diversity are uncertain. Through a comparative and
      quantitative investigation of these two fundamental biological parameters across
      diverse viral taxa, we show that genome length and virion volume conform to a
      simple allometric scaling law. Notably, this allometric relationship holds
      regardless of the type of virus, including those with both RNA and DNA genomes,
      and encompasses viruses that exhibit more than 3 logs of genome size variation.
      Accordingly, this study helps to reveal the basic rules of virus design.

PMID- 24672041
TI  - The Rad6/18 ubiquitin complex interacts with the Epstein-Barr virus
      deubiquitinating enzyme, BPLF1, and contributes to virus infectivity.
AB  - Epstein-Barr virus (EBV) encodes BPLF1, a lytic cycle protein with
      deubiquitinating activity that is contained in its N-terminal domain and
      conserved across the Herpesviridae. EBV replication is associated with cellular
      DNA replication and repair factors, and initiation of EBV lytic replication
      induces a DNA damage response, which can be regulated at least in part by BPLF1.
      The cellular DNA repair pathway, translesion synthesis (TLS), is disrupted by
      BPLF1, which deubiquitinates the DNA processivity factor, PCNA, and inhibits the
      recruitment of the TLS polymerase, polymerase eta (Pol eta), after damage to DNA
      by UV irradiation. Here we showed that the E3 ubiquitin ligase, which activates
      TLS repair by monoubiquitination of PCNA, is also affected by BPLF1
      deubiquitinating activity. First, BPLF1 interacts directly with Rad18, and
      overexpression of BPLF1 results in increased levels of the Rad18 protein,
      suggesting that it stabilizes Rad18. Next, expression of functionally active
      BPLF1 caused relocalization of Rad18 into nuclear foci, which is consistent with
      sites of cellular DNA replication that occur during S phase. Also, levels of
      Rad18 remain constant during lytic reactivation of wild-type virus, but
      reactivation of BPLF1 knockout virus resulted in decreased levels of Rad18.
      Finally, the contribution of Rad18 levels to infectious virus production was
      examined with small interfering RNA (siRNA) targeting Rad18. Results demonstrated
      that reducing levels of Rad18 decreased production of infectious virus, and
      infectious titers of BPLF1 knockout virus were partially restored by
      overexpression of Rad18. Thus, BPLF1 interacts with and maintains Rad18 at high
      levels during lytic replication, which assists in production of infectious virus.
      IMPORTANCE: Characterization of EBV BPLF1's deubiquitinating activity and
      identification of its targets and subsequent functional effects remain little
      studied. All members of the Herpesviridae contain BPLF1 homologs with conserved
      enzymatic activity, and findings discovered with EBV BPLF1 are likely applicable
      to other members of the family. Discovery of new targets of BPLF1 will point to
      cellular pathways and viral processes regulated by the enzymatic activity of the
      EBV-encoded deubiquitinating enzyme. Here we determined the importance of the
      cellular ubiquitin ligase Rad18 in these processes and how it is affected by
      BPLF1. Our findings demonstrate that EBV can co-opt Rad18 as a novel accessory
      factor in the production of infectious virus.

PMID- 24672042
TI  - The tripartite virions of the brome mosaic virus have distinct physical
      properties that affect the timing of the infection process.
AB  - The three subsets of virions that comprise the Brome mosaic virus (BMV) were
      previously thought to be indistinguishable. This work tested the hypothesis that
      distinct capsid-RNA interactions in the BMV virions allow different rates of
      viral RNA release. Several results support distinct interactions between the
      capsid and the BMV genomic RNAs. First, the deletion of the first eight residues
      of the BMV coat protein (CP) resulted in the RNA1-containing particles having
      altered morphologies, while those containing RNA2 were unaffected. Second,
      subsets of the BMV particles separated by density gradients into a pool enriched
      for RNA1 (B1) and for RNA2 and RNA3/4 (B2.3/4) were found to have different
      physiochemical properties. Compared to the B2.3/4 particles, the B1 particles
      were more sensitive to protease digestion and had greater resistivity to
      nanoindentation by atomic force microscopy and increased susceptibility to
      nuclease digestion. Mapping studies showed that portions of the arginine-rich N
      terminal tail of the CP could interact with RNA1. Mutational analysis in the
      putative RNA1-contacting residues severely reduced encapsidation of BMV RNA1
      without affecting the encapsidation of RNA2. Finally, during infection of plants,
      the more easily released RNA1 accumulated to higher levels early in the
      infection. IMPORTANCE: Viruses with genomes packaged in distinct virions could
      theoretically release the genomes at different times to regulate the timing of
      gene expression. Using an RNA virus composed of three particles, we demonstrated
      that the RNA in one of the virions is released more easily than the other two in
      vitro. The differential RNA release is due to distinct interactions between the
      viral capsid protein and the RNAs. The ease of RNA release is also correlated
      with the more rapid accumulation of that RNA in infected plants. Our study
      identified a novel role for capsid-RNA interactions in the regulation of a viral
      infection.

PMID- 24672043
TI  - Impairment of HIV-1 cDNA synthesis by DBR1 knockdown.
AB  - Previous studies showed that short hairpin RNA (shRNA) knockdown of the RNA
      lariat debranching enzyme (DBR1) led to a decrease in the production of HIV-1
      cDNA. To further characterize this effect, DBR1 shRNA was introduced into GHOST
      R5X4 cells, followed by infection at a multiplicity near unity with HIV-1 or an
      HIV-1-derived vector. DNA and RNA were isolated from whole cells and from
      cytoplasmic and nuclear fractions at different times postinfection. Inhibition of
      DBR1 had little or no effect on the formation of minus-strand strong-stop cDNA
      but caused a significant reduction in the formation of intermediate and full
      length cDNA. Moreover, minus-strand strong-stop DNA rapidly accumulated in the
      cytoplasm in the first 2 h of infection but shifted to the nuclear fraction by 6
      h postinfection. Regardless of DBR1 inhibition, greater than 95% of intermediate
      length and full-length HIV-1 cDNA was found in the nuclear fraction at all time
      points. Thus, under these experimental conditions, HIV-1 cDNA synthesis was
      initiated in the cytoplasm and completed in the nucleus or perinuclear region of
      the infected cell. When nuclear import of the HIV-1 reverse transcription complex
      was blocked by expressing a truncated form of the mRNA cleavage and
      polyadenylation factor CPSF6, the completion of HIV-1 vector cDNA synthesis was
      detected in the cytoplasm, where it was not inhibited by DBR1 knockdown.
      Refinement of the cell fractionation procedure indicated that the completion of
      reverse transcription occurred both within nuclei and in the perinuclear region.
      Taken together the results indicate that in infections at a multiplicity near 1,
      HIV-1 reverse transcription is completed in the nucleus or perinuclear region of
      the infected cell, where it is dependent on DBR1. When nuclear transport is
      inhibited, reverse transcription is completed in the cytoplasm in a DBR1
      independent manner. Thus, there are at least two mechanisms of HIV-1 reverse
      transcription that require different factors and occur in different intracellular
      locations. IMPORTANCE: This study shows that HIV-1 reverse transcription starts
      in the cytoplasm but is completed in or on the surface of the nucleus. Moreover,
      we show that nuclear reverse transcription is dependent on the activity of the
      human RNA lariat debranchng enzyme (DBR1), while cytoplasmic reverse
      transcription is not. These findings may provide new avenues for inhibiting HIV-1
      replication and therefore may lead to new medicines for treating HIV-1-infected
      individuals.

PMID- 24672044
TI  - A complex comprising phosphatidylinositol 4-kinase IIIbeta, ACBD3, and Aichi
      virus proteins enhances phosphatidylinositol 4-phosphate synthesis and is
      critical for formation of the viral replication complex.
AB  - Phosphatidylinositol 4-kinase IIIbeta (PI4KB) is a host factor required for the
      replication of certain picornavirus genomes. We previously showed that
      nonstructural proteins 2B, 2BC, 2C, 3A, and 3AB of Aichi virus (AiV), a
      picornavirus, interact with the Golgi protein, acyl-coenzyme A binding domain
      containing 3 (ACBD3), which interacts with PI4KB. These five viral proteins,
      ACBD3, PI4KB, and the PI4KB product phosphatidylinositol 4-phosphate (PI4P)
      colocalize to the AiV RNA replication sites (J. Sasaki et al., EMBO J. 31:754
      766, 2012). We here examined the roles of these viral and cellular molecules in
      the formation of AiV replication complexes. Immunofluorescence microscopy
      revealed that treatment of AiV polyprotein-expressing cells with a small
      interfering RNA targeting ACBD3 abolished colocalization of the viral 2B, 2C, and
      3A proteins with PI4KB. A PI4KB-specific inhibitor also prevented their
      colocalization. Virus RNA replication increased the level of cellular PI4P
      without affecting that of PI4KB, and individual expression of 2B, 2BC, 2C, 3A, or
      3AB stimulated PI4P generation. These results suggest that the viral
      protein/ACBD3/PI4KB complex plays an important role in forming the functional
      replication complex by enhancing PI4P synthesis. Of the viral proteins, 3A and
      3AB were shown to stimulate the in vitro kinase activity of PI4KB through forming
      a 3A or 3AB/ACBD3/PI4KB complex, whereas the ACBD3-mediated PI4KB activation by
      2B and 2C remains to be demonstrated. IMPORTANCE: The phosphatidylinositol 4
      kinase PI4KB is a host factor required for the replication of certain
      picornavirus genomes. Aichi virus, a picornavirus belonging to the genus
      Kobuvirus, forms a complex comprising one of the viral nonstructural proteins 2B,
      2BC, 2C, 3A, and 3AB, the Golgi protein ACBD3, and PI4KB to synthesize PI4P at
      the sites for viral RNA replication. However, the roles of this protein complex
      in forming the replication complex are unknown. This study showed that virus RNA
      replication and individual viral proteins enhance the level of cellular PI4P, and
      suggested that the viral protein/ACBD3/PI4KB complex plays an important role in
      forming a functional replication complex. Thus, the present study provides a new
      example of modulation of cellular lipid metabolism by viruses to support the
      replication of their genomes.

PMID- 24672045
TI  - Identification of a novel rhabdovirus in Spodoptera frugiperda cell lines.
AB  - The Sf9 cell line, derived from Spodoptera frugiperda, is used as a cell
      substrate for biological products, and no viruses have been reported in this cell
      line after extensive testing. We used degenerate PCR assays and massively
      parallel sequencing (MPS) to identify a novel RNA virus belonging to the order
      Mononegavirales in Sf9 cells. Sequence analysis of the assembled virus genome
      showed the presence of five open reading frames (ORFs) corresponding to the genes
      for the N, P, M, G, and L proteins in other rhabdoviruses and an unknown ORF of
      111 amino acids located between the G- and L-protein genes. BLAST searches
      indicated that the S. frugiperda rhabdovirus (Sf-rhabdovirus) was related in a
      limited region of the L-protein gene to Taastrup virus, a newly discovered member
      of the Mononegavirales from a leafhopper (Hemiptera), and also to plant
      rhabdoviruses, particularly in the genus Cytorhabdovirus. Phylogenetic analysis
      of sequences in the L-protein gene indicated that Sf-rhabdovirus is a novel virus
      that branched with Taastrup virus. Rhabdovirus morphology was confirmed by
      transmission electron microscopy of filtered supernatant samples from Sf9 cells.
      Infectivity studies indicated potential transient infection by Sf-rhabdovirus in
      other insect cell lines, but there was no evidence of entry or virus replication
      in human cell lines. Sf-rhabdovirus sequences were also found in the Sf21
      parental cell line of Sf9 cells but not in other insect cell lines, such as BT1
      TN-5B1-4 (Tn5; High Five) cells and Schneider's Drosophila line 2 [D.Mel.(2);
      SL2] cells, indicating a species-specific infection. The results indicate that
      conventional methods may be complemented by state-of-the-art technologies with
      extensive bioinformatics analysis for identification of novel viruses.
      IMPORTANCE: The Spodoptera frugiperda Sf9 cell line is used as a cell substrate
      for the development and manufacture of biological products. Extensive testing has
      not previously identified any viruses in this cell line. This paper reports on
      the identification and characterization of a novel rhabdovirus in Sf9 cells. This
      was accomplished through the use of next-generation sequencing platforms, de novo
      assembly tools, and extensive bioinformatics analysis. Rhabdovirus identification
      was further confirmed by transmission electron microscopy. Infectivity studies
      showed the lack of replication of Sf-rhabdovirus in human cell lines. The overall
      study highlights the use of a combinatorial testing approach including
      conventional methods and new technologies for evaluation of cell lines for
      unexpected viruses and use of comprehensive bioinformatics strategies for
      obtaining confident next-generation sequencing results.

PMID- 24672046
TI  - Coregulatory interactions among CD8alpha dendritic cells, the latency-associated
      transcript, and programmed death 1 contribute to higher levels of herpes simplex
      virus 1 latency.
AB  - The latency-associated transcript (LAT) of herpes simplex virus 1 (HSV-1),
      CD8alpha(+) dendritic cells (DCs), and programmed death 1 (PD-1) have all been
      implicated in the HSV-1 latency-reactivation cycle. It is not known, however,
      whether an interaction between LAT and CD8alpha(+) DCs regulates latency and T
      cell exhaustion. To address this question, we used LAT-expressing [LAT(+)] and
      LAT-negative [LAT(-)] viruses. Depletion of DCs in mice ocularly infected with
      LAT(+) virus resulted in a reduction in the number of T cells expressing PD-1 in
      the trigeminal ganglia (TG), whereas depletion of DCs in mice similarly infected
      with LAT(-) virus did not alter PD-1 expression. CD8alpha(+) DCs, but not CD4(+)
      DCs, infected with LAT(+) virus had higher levels of ICP0, ICP4, thymidine kinase
      (TK), and PD-1 ligand 1 (PD-L1) transcripts than those infected with LAT(-)
      virus. Coculture of infected bone marrow (BM)-derived DCs from wild-type (WT)
      mice, but not infected DCs from CD8alpha(-/-) mice, with WT naive T cells
      contributed to an increase in PD-1 expression. Transfer of bone marrow from WT
      mice but not CD8alpha(-/-) mice to recipient Rag1(-/-) mice increased the number
      of latent viral genomes in reconstituted mice infected with the LAT(+) virus.
      Collectively, these data indicated that a reduction in latency correlated with a
      decline in the levels of CD8alpha(+) DCs and PD-1 expression. In summary, our
      results demonstrate an interaction among LAT, PD-1, and CD11c CD8alpha(+) cells
      that regulates latency in the TG of HSV-1-infected mice. IMPORTANCE: Very little
      is known regarding the interrelationship of LAT, PD-1, and CD8alpha(+) DCs and
      how such interactions might contribute to relative numbers of latent viral
      genomes. We show here that (i) in both in vivo and in vitro studies, deficiency
      of CD8alpha(+) DCs significantly reduced T-cell exhaustion in the presence of
      LAT(+) virus but not LAT(-) virus; (ii) HSV-1 infectivity was significantly lower
      in LAT(-)-infected DCs than in their LAT(+)-infected counterparts; and (iii)
      adoptive transfer of bone marrow (BM) from WT but not CD8alpha(-/-) mice to
      recipient Rag1(-/-) mice restored latency to the level in WT mice following
      infection with LAT(+) virus. These studies point to a key role for CD8alpha(+)
      DCs in T-cell exhaustion in the presence of LAT, which leads to larger numbers of
      latent viral genomes. Thus, altering this negative function of CD8alpha(+) DCs
      can potentially be used to generate a more effective vaccine against HSV
      infection.

PMID- 24672047
TI  - The human metapneumovirus small hydrophobic protein has properties consistent
      with those of a viroporin and can modulate viral fusogenic activity.
AB  - Human metapneumovirus (HMPV) encodes three glycoproteins: the glycoprotein, which
      plays a role in glycosaminoglycan binding, the fusion (F) protein, which is
      necessary and sufficient for both viral binding to the target cell and fusion
      between the cellular plasma membrane and the viral membrane, and the small
      hydrophobic (SH) protein, whose function is unclear. The SH protein of the
      closely related respiratory syncytial virus has been suggested to function as a
      viroporin, as it forms oligomeric structures consistent with a pore and alters
      membrane permeability. Our analysis indicates that both the full-length HMPV SH
      protein and the isolated SH protein transmembrane domain can associate into
      higher-order oligomers. In addition, HMPV SH expression resulted in increases in
      permeability to hygromycin B and alteration of subcellular localization of a
      fluorescent dye, indicating that SH affects membrane permeability. These results
      suggest that the HMPV SH protein has several characteristics consistent with a
      putative viroporin. Interestingly, we also report that expression of the HMPV SH
      protein can significantly decrease HMPV F protein-promoted membrane fusion
      activity, with the SH extracellular domain and transmembrane domain playing a key
      role in this inhibition. These results suggest that the HMPV SH protein could
      regulate both membrane permeability and fusion protein function during viral
      infection. IMPORTANCE: Human metapneumovirus (HMPV), first identified in 2001, is
      a causative agent of severe respiratory tract disease worldwide. The small
      hydrophobic (SH) protein is one of three glycoproteins encoded by all strains of
      HMPV, but the function of the HMPV SH protein is unknown. We have determined that
      the HMPV SH protein can alter the permeability of cellular membranes, suggesting
      that HMPV SH is a member of a class of proteins termed viroporins, which modulate
      membrane permeability to facilitate critical steps in a viral life cycle. We also
      demonstrated that HMPV SH can inhibit the membrane fusion function of the HMPV
      fusion protein. This work suggests that the HMPV SH protein has several
      functions, though the steps in the HMPV life cycle impacted by these functions
      remain to be clarified.

PMID- 24672048
TI  - Enterovirus 68 3C protease cleaves TRIF to attenuate antiviral responses mediated
      by Toll-like receptor 3.
AB  - Human enterovirus 68 (EV68) is a member of the EV-D species, which belongs to the
      EV genus of the Picornaviridae family. Over the past several years, there have
      been increasingly documented outbreaks of respiratory disease associated with
      EV68. As a globally emerging pathogen, EV68 infects both adults and children.
      However, the molecular basis of EV68 pathogenesis is unknown. Here we report that
      EV68 inhibits Toll-like receptor 3 (TLR3)-mediated innate immune responses by
      targeting the TIR domain-containing adaptor inducing beta interferon (TRIF). In
      infected HeLa cells, EV68 inhibits poly(I.C)-induced interferon regulatory factor
      3 (IRF3) activation and beta interferon (IFN-beta) expression. Further
      investigations revealed that TRIF, a critical adaptor downstream of TLR3, is
      targeted by EV68. When expressed alone, 3C(pro), an EV68-encoded protease,
      cleaves TRIF. 3C(pro) mediates TRIF cleavage at Q312 and Q653, which are sites in
      the amino- and carboxyl-terminal domains, respectively. This cleavage relies on
      3C(pro)'s cysteine protease activity. Cleavage of TRIF abolishes the capacity of
      TRIF to activate NF-kappaB and IFN-beta signaling. These results suggest that
      control of TRIF by 3C(pro) may be a mechanism by which EV68 subverts host innate
      immune responses. IMPORTANCE: EV68 is a globally emerging pathogen, but the
      molecular basis of EV68 pathogenesis is unclear. Here we report that EV68
      inhibits TLR3-mediated innate immune responses by targeting TRIF. Further
      investigations revealed that TRIF is cleaved by 3C(pro). These results suggest
      that control of TRIF by 3C(pro) may be a mechanism by which EV68 impairs type I
      IFN production in response to TLR3 activation.

PMID- 24672049
TI  - Reduced prevalence of HBsAg variants following a successful immunization program
      in China.

PMID- 24672050
TI  - Heparan sulfate in baculovirus binding and entry of mammalian cells.

PMID- 24672051
TI  - Reply to "heparan sulfate in baculovirus binding and entry of Mammalian cells".

PMID- 24672053
TI  - Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and
      lamin B2.
AB  - Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed
      ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after
      birth with neuronal layering abnormalities in the cerebral cortex, a consequence
      of defective neuronal migration. The similarities in amino acid sequences,
      expression patterns, and knockout phenotypes raise the question of whether the
      two proteins have redundant functions. To investigate this topic, we generated
      "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus
      (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)).
      Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they
      died soon after birth with neuronal layering abnormalities in the cerebral
      cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in
      Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially
      ameliorate the abnormalities associated with lamin B1 deficiency. Similarly,
      increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the
      neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that
      lamins B1 and B2 have unique roles in the developing brain and that increased
      production of one B-type lamin does not fully complement loss of the other. 

PMID- 24672054
TI  - The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and store-operated
      calcium entry (SOCE).
AB  - Store-operated calcium entry (SOCE) is the predominant Ca(2+) entry mechanism in
      nonexcitable cells and controls a variety of physiological and pathological
      processes. Although significant progress has been made in identifying the
      components required for SOCE, the molecular mechanisms underlying it are elusive.
      The present study provides evidence for a direct involvement of kinase suppressor
      of Ras 2 (KSR2) in SOCE. Using lymphocytes and fibroblasts from ksr2(-/-) mice
      and shKSR2-depleted cells, we find that KSR2 is critical for the elevation of
      cytosolic Ca(2+) concentration. Specifically, our results show that although it
      is dispensable for Ca(2+)-store depletion, KSR2 is required for optimal calcium
      entry. We observe that KSR2 deficiency affects stromal interaction molecule 1
      (STIM1)/ORAI1 puncta formation, which is correlated with cytoskeleton
      disorganization. Of interest, we find that KSR2-associated calcineurin is crucial
      for SOCE. Blocking calcineurin activity impairs STIM1/ORAI1 puncta-like formation
      and cytoskeleton organization. In addition, we observe that calcineurin activity
      and its role in SOCE are both KSR2 dependent. 

PMID- 24672055
TI  - Trans-dimerization of JAM-A regulates Rap2 and is mediated by a domain that is
      distinct from the cis-dimerization interface.
AB  - Junctional adhesion molecule-A (JAM-A) is a tight junction-associated signaling
      protein that regulates epithelial cell proliferation, migration, and barrier
      function. JAM-A dimerization on a common cell surface (in cis) has been shown to
      regulate cell migration, and evidence suggests that JAM-A may form homodimers
      between cells (in trans). Indeed, transfection experiments revealed accumulation
      of JAM-A at sites between transfected cells, which was lost in cells expressing
      cis- or predicted trans-dimerization null mutants. Of importance, microspheres
      coated with JAM-A containing alanine substitutions to residues 43NNP45 (NNP-JAM
      A) within the predicted trans-dimerization site did not aggregate. In contrast,
      beads coated with cis-null JAM-A demonstrated enhanced clustering similar to that
      observed with wild-type (WT) JAM-A. In addition, atomic force microscopy revealed
      decreased association forces in NNP-JAM-A compared with WT and cis-null JAM-A.
      Assessment of effects of JAM-A dimerization on cell signaling revealed that
      expression of trans- but not cis-null JAM-A mutants decreased Rap2 activity.
      Furthermore, confluent cells, which enable trans-dimerization, had enhanced Rap2
      activity. Taken together, these results suggest that trans-dimerization of JAM-A
      occurs at a unique site and with different affinity compared with dimerization in
      cis. Trans-dimerization of JAM-A may thus act as a barrier-inducing molecular
      switch that is activated when cells become confluent. 

PMID- 24672056
TI  - LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive
      endosomes.
AB  - Neurons extend two types of neurites-axons and dendrites-that differ in structure
      and function. Although it is well understood that the cytoskeleton plays a
      pivotal role in neurite differentiation and extension, the mechanisms by which
      membrane components are supplied to growing axons or dendrites is largely
      unknown. We previously reported that the membrane supply to axons is regulated by
      lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the
      role of LMTK1 in dendrite formation. Down-regulation of LMTK1 increases dendrite
      growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1
      knockout significantly enhances the prevalence, velocity, and run length of
      anterograde movement of Rab11A-positive endosomes to levels similar to those
      expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics
      also increases in the cell body and growth cone of LMTK1-deficient neurons.
      Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation
      site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls
      dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5
      dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory
      mechanism of dendrite development as well as axon outgrowth. 

PMID- 24672057
TI  - Nedd8-activating enzyme inhibitor MLN4924 provides synergy with mitomycin C
      through interactions with ATR, BRCA1/BRCA2, and chromatin dynamics pathways.
AB  - MLN4924 is an investigational small-molecule inhibitor of the Nedd8-activating
      enzyme currently in phase I clinical trials. MLN4924 induces DNA damage via
      rereplication in most cell lines. This distinct mechanism of DNA damage may
      affect its ability to combine with standard-of-care agents and may affect the
      clinical development of MLN4924. As such, we studied its interaction with other
      DNA-damaging agents. Mitomycin C, cisplatin, cytarabine, UV radiation, SN-38, and
      gemcitabine demonstrated synergy in combination with MLN4924 in vitro. The
      combination of mitomycin C and MLN4924 was shown to be synergistic in a mouse
      xenograft model. Importantly, depletion of genes within the ataxia telangiectasia
      and Rad3 related (ATR) and BRCA1/BRCA2 pathways, chromatin modification, and
      transcription-coupled repair reduced the synergy between mitomycin C and MLN4924.
      In addition, comet assay demonstrated increased DNA strand breaks with the
      combination of MLN4924 and mitomycin C. Our data suggest that mitomycin C causes
      stalled replication forks, which when combined with rereplication induced by
      MLN4924 results in frequent replication fork collisions, leading to cell death.
      This study provides a straightforward approach to understand the mechanism of
      synergy, which may provide useful information for the clinical development of
      these combinations.

PMID- 24672058
TI  - Antitumor activity of 7-aminocarboxycoumarin derivatives, a new class of potent
      inhibitors of lactate influx but not efflux.
AB  - High lactate concentration in tumors is associated with bad prognosis. Lactate is
      released by glycolytic cells in tumors and recaptured by oxidative cancer cells
      to feed the tricarboxylic acid (TCA) cycle after conversion into pyruvate.
      Monocarboxylate transporters (MCT) mediate these fluxes of proton-linked lactate
      and represent attractive targets to interrupt lactate shuttle and to inhibit
      tumor growth. Here, we investigated the properties of 7-aminocarboxycoumarins
      (7ACC) developed to selectively interfere with lactate fluxes in the lactate-rich
      tumor microenvironment. The pharmacologic properties of two compounds of this
      family, including their effects on lactate influx and efflux and antitumor
      activity, were investigated using human cancer cell lines and mouse xenograft
      models. Contrary to the reference MCT1 inhibitor AR-C155858, 7ACC unexpectedly
      inhibited lactate influx but not efflux in tumor cells expressing MCT1 and MCT4
      transporters. 7ACC delayed the growth of cervix SiHa tumors, colorectal HCT116
      tumors, and orthoptopic MCF-7 breast tumors. MCT target engagement was confirmed
      by the lack of activity of 7ACC on bladder UM-UC-3 carcinoma that does not
      express functional MCT. 7ACC also inhibited SiHa tumor relapse after treatment
      with cisplatin. Finally, we found that contrary to AR-C155858, 7ACC did not
      prevent the cell entry of the substrate-mimetic drug 3-bromopyruvate (3BP)
      through MCT1, and contributed to the inhibition of tumor relapse after 3BP
      treatment. In conclusion, our results indicate that 7ACC selectively affects a
      single part of the MCT symporter translocation cycle, leading to strict
      inhibition of lactate influx. This singular activity is associated with antitumor
      effects less prone to resistance and side effects.

PMID- 24672059
TI  - New questions for pharmacists in the health care system.

PMID- 24672060
TI  - Use of humor to enhance learning: bull's eye or off the mark.

PMID- 24672061
TI  - Evolution of self-care education.
AB  - During the past 15 years, the curriculum content for nonprescription medication
      and self-care therapeutics has expanded significantly. Self-care courses ranging
      from stand-alone, required courses to therapeutic content and skills
      laboratories, have evolved in colleges and schools of pharmacy to accommodate
      rapid changes related to nonprescription medications and to meet the needs of
      students. The design of and content delivery methods used in self-care courses
      vary among institutions. Teaching innovations such as team-based learning, role
      playing/vignettes, videos, and social media, as well as interdisciplinary
      learning have enhanced delivery of this content. Given that faculty members train
      future pharmacists, they should be familiar with the new paradigms of
      Nonprescription Safe Use Regulatory Expansion (NSURE) Initiative, nonprescription
      medications for chronic diseases, and the growing trends of health and wellness
      in advancing patient-care initiatives. This paper reviews the significant changes
      that may be impacting self-care curriculums in the United States. 

PMID- 24672062
TI  - A mentoring program to help junior faculty members achieve scholarship success.
AB  - The University of North Carolina Eshelman School of Pharmacy launched the Bill
      and Karen Campbell Faculty Mentoring Program (CMP) in 2006 to support scholarship
      intensive junior faculty members. This report describes the origin, expectations,
      principles, and best practices that led to the introduction of the program,
      reviews the operational methods chosen for its implementation, provides
      information about its successes, and analyzes its strengths and limitations. 

PMID- 24672063
TI  - Alcohol use behaviors among pharmacy students.
AB  - OBJECTIVE: To identify reasons for drinking, determine the patterns of alcohol
      abuse, and explore relationships between drinking motives and alcohol abuse
      patterns in pharmacy students. METHODS: A cross-sectional anonymous, voluntary,
      self-administered paper survey instrument was administered to first-year (P1)
      through third-year (P3) pharmacy students as part of a professional seminar.
      RESULTS: Survey instruments were completed by 349 pharmacy students (95.9%
      cooperation rate). Using the Alcohol Use Disorders Identification Test criteria,
      23.2% of students reported hazardous or harmful use and 67.2% of students
      reported consuming alcohol at hazardous levels during the past year. Students who
      were male (37.0%), single (25.3%), and attended the main campus (26.2%) were more
      likely than their counterparts to report hazardous or harmful alcohol use.
      Pharmacy students reported social motives as the most common reason for drinking;
      however, coping and enhancement motives were more predictive of harmful or
      hazardous alcohol use. CONCLUSION: Approximately 1 in 4 pharmacy students (23%)
      reported hazardous or harmful alcohol use. Education about the dangers of alcohol
      abuse and intervention programs from colleges and schools of pharmacy are
      recommended to help address this issue.

PMID- 24672064
TI  - Pharmacy students' perceptions of cultural competence encounters during practice
      experiences.
AB  - OBJECTIVE: To determine pharmacy students' perceptions regarding cultural
      competence training, cross-cultural experiences during advanced pharmacy practice
      experiences (APPEs), and perceived comfort levels with various cultural
      encounters. METHODS: Fourth-year pharmacy (P4) students were asked to complete a
      questionnaire at the end of their fourth APPE. RESULTS: Fifty-two of 124
      respondents (31.9%) reported having 1 or more cultural competence events during
      their APPEs, the most common of which was caring for a patient with limited
      English proficiency. CONCLUSION: Students reported high levels of comfort with
      specific types of cultural encounters (disabilities, sexuality, financial
      barriers, mental health), but reported to be less comfortable in other
      situations.

PMID- 24672065
TI  - Pharmacy student self-testing as a predictor of examination performance.
AB  - OBJECTIVES: To determine if student self-testing improves performance during a
      doctor of pharmacy course. METHODS: Students were given access to online quizzes
      with a large pool of randomly selected questions specific to upcoming examination
      content. Quizzes were electronically scored immediately upon completion and
      students were provided corrective feedback. RESULTS: Examination scores following
      implementation of the practice quizzes were significantly higher in all but the
      last testing period. The upper fiftieth percentile of students scored higher on
      both the practice quizzes and subsequent examinations in all but the fourth
      testing period. CONCLUSIONS: Providing pharmacy students with self-testing
      opportunities could increase their retention of course material and provide
      feedback to both students and educators regarding learning, as well as provide
      students with a measure of their metacognition.

PMID- 24672066
TI  - Pharmacy students' ability to identify plagiarism after an educational
      intervention.
AB  - Objective. To determine if an educational intervention in a doctor of pharmacy
      (PharmD) degree program increases pharmacy students' ability to identify
      plagiarism. Methods. First-year (P1), second-year (P2), and third-year (P3)
      pharmacy students attended an education session during which types of plagiarism
      and methods for avoiding plagiarism were reviewed. Students completed a
      preintervention assessment immediately prior to the session and a
      postintervention assessment the following semester to measure their ability.
      Results. Two hundred fifty-two students completed both preintervention and
      postintervention assessments. There was a 4% increase from preintervention to
      postintervention in assessment scores for the overall student sample (p<0.05).
      The mean change was greatest for P1 and P2 students (5% and 4.8%, respectively).
      Conclusion. An educational intervention about plagiarism can significantly
      improve students' ability to identify plagiarism. 

PMID- 24672067
TI  - Impact of students pharmacists on the medication reconciliation process in high
      risk hospitalized general medicine patients.
AB  - OBJECTIVE" To compare the accuracy of medication lists obtained by student
      pharmacists, nurses, and physicians, and quantify the number of discrepancies
      identified as part of the medication reconciliation process. METHODS: Between May
      and July 2012, patients admitted to an internal medicine team at a 350-bed
      tertiary academic medical center were assessed for inclusion in the study.
      Physicians and/or nurses conducted medication reviews for these patients at the
      time of admission, while student pharmacists conducted medication reconciliation.
      RESULTS: Eighty-six patients were assessed, and 52 met all inclusion criteria. A
      total of 268 discrepancies were identified as part of the medication
      reconciliation performed by the student pharmacists, approximating 5
      discrepancies per patient (range 0-13). Student pharmacists identified 532
      preadmission medications, significantly more than did nurses (355) or physicians
      (368), p=0.006. CONCLUSION: Student pharmacists, with appropriate oversight, can
      be used in several tasks that previously may have been designated to pharmacists
      only, such as medication reconciliation.

PMID- 24672069
TI  - Moral development of first-year pharmacy students in the United Kingdom.
AB  - OBJECTIVE: To investigate the moral development of pharmacy students over their
      first academic year of study at a university in the United Kingdom. METHODS:
      Pharmacy students completed Defining Issues Test (DIT) at the start of their
      first year (phase 1) and again at the end of their first year (phase 2) of the
      program. RESULTS: Pharmacy students (N=116) had significantly higher moral
      reasoning at the beginning of their first year than by the end of it. Scores
      differed by students' gender and age; however, these findings differed between
      phase 1 and phase 2. CONCLUSION: First-year pharmacy students in the United
      Kingdom scored lower on moral reasoning than did pharmacy students in the United
      States and Canada.

PMID- 24672068
TI  - Pharmacy student self-perception of weight and relationship to counseling
      patients on lifestyle modification.
AB  - OBJECTIVE: To assess the accuracy of pharmacy students' self-assessment of body
      mass index (BMI) and determine the relationship of this to comfort level in
      counseling patients regarding lifestyle modification. METHODS: A prospective,
      observational, cohort study was conducted that included first-, second-, and
      third-year pharmacy students who had previously undergone training in BMI self
      assessment. Data on students' weight and height were collected and a survey that
      contained questions on self-perception of body weight and comfort with lifestyle
      counseling was conducted. Perceived BMI categories (underweight, normal,
      overweight, and obese) were then compared to actual calculated BMI to determine
      the accuracy of the student's self-perception. RESULTS: At baseline,
      participants' accuracy in self-assessment of BMI was 74%, 73.3%, and 75.6%
      respectively, for first-, second-, and third-year students (p=0.911). Students
      accuracy increased but not significantly as they progressed through the
      curriculum (7.2% and 13.3%, respectively; p=0.470 and p=0.209). Neither accuracy
      in self-assessment of BMI nor students' actual BMI significantly affected
      students' comfort level with lifestyle modification counseling within healthy
      weight, overweight, or obese patient categories. However, as the patients' BMI
      category increased, comfort level differences were observed among students of
      normal and overweight categories. CONCLUSION: Patients' BMI category may be a
      significant barrier to pharmacy students' comfort level in providing lifestyle
      modification counseling. This finding suggests the need to implement curriculum
      changes to better prepare students for lifestyle modification counseling.

PMID- 24672070
TI  - Laboratory exercises to teach clinically relevant chemistry of antibiotics.
AB  - OBJECTIVES: To design, implement, and evaluate student performance on clinically
      relevant chemical and spectral laboratory exercises on antibiotics. DESIGN: In
      the first of 2 exercises, second-year pharmacy students enrolled in an integrated
      laboratory sequence course studied the aqueous stability of beta-lactam
      antibiotics using a spectral visual approach. In a second exercise, students
      studied the tendency of tetracycline, rifamycins, and fluoroquinolones to form
      insoluble chelate complexes (turbidity) with polyvalent metals. ASSESSMENT: On a
      survey to assess achievement of class learning objectives, students agreed the
      laboratory activities helped them better retain important information concerning
      antibiotic stability and interactions. A significant improvement was observed in
      performance on examination questions related to the laboratory topics for 2012
      and 2013 students compared to 2011 students who did not complete the laboratory.
      A 1-year follow-up examination question administered in a separate course showed
      >75% of the students were able to identify rifamycins-food interactions compared
      with <25% of students who had not completed the laboratory exercises. CONCLUSION:
      The use of spectral visual approaches allowed students to investigate antibiotic
      stability and interactions, thus reinforcing the clinical relevance of medicinal
      chemistry. Students' performance on questions at the 1-year follow-up suggested
      increased retention of the concepts learned as a result of completing the
      exercises.

PMID- 24672071
TI  - Student-peer mentoring on a drug information response.
AB  - OBJECTIVE: To implement a student peer-mentoring program with a drug information
      response assignment in an introductory pharmacy practice course. DESIGN: Second
      year student pharmacists (P2 mentors) enrolled in an independent study course
      were randomly assigned first-year student pharmacists (P1 mentees) to mentor on a
      drug information assignment. The P2 mentors provided feedback to P1 mentees'
      assignment drafts. The P1 mentees had the opportunity to revise the draft prior
      to turning in the completed assignment to course faculty members for grading.
      ASSESSMENT: Both P1 mentees and P2 mentors agreed the mentorship improved their
      ability to prepare a drug information response (76% and 100%, respectively). A
      majority of the student pharmacists would choose to be involved in the program
      again. CONCLUSION: The student peer-mentoring program was successful in improving
      student pharmacists' perceptions of ability to compose a drug information
      response.

PMID- 24672072
TI  - Pharmacy students' attitudes about treating patients with alcohol addiction after
      attending a required mutual support group.
AB  - OBJECTIVE: To implement required attendance at mutual support groups for
      addiction recovery as a pharmacy skills laboratory exercise, and to evaluate how
      attendance affected pharmacy students' attitudes about caring for patients with
      addiction. DESIGN: Third-year (P3) pharmacy students enrolled in a Pharmacy
      Skills Laboratory course were required to watch an introductory video about
      Alcoholics Anonymous (AA) and then attend 2 "open meetings" during the semester.
      Students submitted a written reflection as proof of attendance. ASSESSMENT:
      Pharmacy students who agreed to participate in the study completed the Short
      Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ) during the course
      orientation and again at the end of the semester. Mutual support group attendance
      significantly affected the students' attitudes within the domains of role
      adequacy, task specific self-esteem, and work satisfaction. Significant changes
      were not observed within the domains of motivation and role legitimacy.
      CONCLUSION: Mutual support group attendance exposed pharmacy students to the
      negative effects of alcohol abuse and increased their self-confidence to provide
      care to patients with alcohol addiction.

PMID- 24672073
TI  - "Brown bag" simulations to teach drug utilization review.
AB  - OBJECTIVE: To teach drug utilization review (DUR) skills to pharmacy students and
      assess their abilities and confidence before and after training. DESIGN: Profile
      reviews and online and live drug-utilization-review activities of increasing
      difficulty were incorporated into the first (P1), second (P2), and third (P3)
      years of the Pharmacy Skills Training Laboratory sequence in a doctor of pharmacy
      (PharmD) curriculum. ASSESSMENT: An online survey instrument was administered to
      gauge how comfortable students were with specific DUR skills before and after the
      activities. Students' confidence in performing specific DUR skills improved after
      completing the activities. CONCLUSION: Profile reviews, as well as online and
      live medication reviews, gave students numerous opportunities to practice drug
      utilization review skills throughout the first 3 years of the pharmacy
      curriculum. Students' confidence in performing specific drug utilization review
      skills improved after the activities. Students' ability to perform the skills
      also improved as measured with the developed checklist in section V and VI of the
      Pharmacy Skills Laboratory sequence.

PMID- 24672074
TI  - Simulated drug discovery process to conduct a synoptic assessment of pharmacy
      students.
AB  - OBJECTIVE. To implement and assess a task-based learning exercise that prompts
      pharmacy students to integrate their understanding of different disciplines.
      DESIGN. Master of pharmacy (MPharm degree) students were provided with simulated
      information from several preclinical science and from clinical trials and asked
      to synthesize this into a marketing authorization application for a new drug.
      Students made a link to pharmacy practice by creating an advice leaflet for
      pharmacists. ASSESSMENT. Students' ability to integrate information from
      different disciplines was evaluated by oral examination. In 2 successive academic
      years, 96% and 82% of students demonstrated an integrated understanding of their
      proposed new drug. Students indicated in a survey that their understanding of the
      links between different subjects improved. CONCLUSION. Simulated drug discovery
      provides a learning environment that emphasizes the connectivity of the
      preclinical sciences with each other and the practice of pharmacy.

PMID- 24672075
TI  - Responses to "Is it time to start teaching basic diagnostics?".

PMID- 24672076
TI  - Primary care pharmacists: provision of clinical-decision services in healthcare.

PMID- 24672077
TI  - Academic entitlement: a student's perspective.

PMID- 24672078
TI  - Pharmacy education in the United Arab Emirates.

PMID- 24672079
TI  - Community-acquired pneumonia in an aging population.

PMID- 24672080
TI  - Effects of simvastatin on blood pressure in hypercholesterolemic patients: An
      open-label study in patients with hypertension or normotension.
AB  - BACKGROUND: Simvastatin has been reported to improve endotheliumdependent
      vascular relaxation in patients with hypercholesterolemia. The consequent
      decrease in arterial stiffness might be associated with a decrease in blood
      pressure (BP). OBJECTIVE: The aim of this study was to determine whether
      simvastatin 20 and 40 mg/d have an effect on systolic and diastolic blood
      pressure (SBP and DBP, respectively) in patients with hypercholesterolemia, and,
      if so, whether the effect is dose dependent and/or is related to the changes in
      the serum lipid profile. METHODS: This 6-month, open-label study was conducted at
      the Lipid Clinics of the Department of Internal Medicine, University of Milan,
      Maggiore Hospital IRCCS, and of the Department of Internal Medicine 1, G. Salvini
      Hospital, Garbagnate Milanese (Milan, Italy). Patients aged 18 to 80 years with
      primary hypercholesterolemia who were following a low-fat, low-cholesterol diet
      for >2 months before the study were enrolled. Patients at high risk for
      cardiovascular disease (CVD), according to the National Cholesterol Education
      Program Adult Treatment Panel II guidelines, were given simvastatin 20 mg
      (tablet) QD for 3 months, and those at low risk for CVD continued with diet only
      for 3 months (controls). Efficacy variables included body weight, SBP, DBP, and
      serum lipid levels (total cholesterol [TC], low-density lipoprotein cholesterol
      [LDL-C], high density lipoprotein cholesterol [HDL-C], and triglycerides [TG]).
      At 3 months, patients in the simvastatin + diet group who reached their
      therapeutic goal continued to receive simvastatin 20 mg/d for 3 additional
      months. In simvastatintreated patients who were normotensive at baseline or who
      became normotensive at 3 months but who did not reach the therapeutic goal, the
      simvastatin dosage was increased to 40 mg/d. Patients in both groups who remained
      hypertensive at 3 months were switched to hypotensive therapy. In the diet-only
      group, patients who were formerly normotensive or who became normotensive at 3
      months but who did not reach their therapeutic goal continued with diet only or
      started lipid-lowering therapy. All other patients in the diet-only group
      continued to be treated with diet only, for 3 additional months. Efficacy
      variables were measured again at 6 months. Tolerability of simvastatin was
      assessed at each visit using patient interview and measurement of serum
      aminotransferase and creatine phosphokinase levels. RESULTS: The study population
      comprised 222 patients (132 women, 90 men; mean [SEM] age, 53.9 [0.95] years
      [range, 23-76 years]); 115 high-risk patients (57 with untreated stage 1
      hypertension) were assigned to the simvastatin + diet group, and 107 low-risk
      patients (29 with untreated stage 1 hypertension) were assigned to the diet-only
      group. In the simvastatin group, after 3 months of therapy, mean SBP was
      decreased by 3.9 (1.49) mm Hg (change, -2.9%), mean DBP decreased by 3.0 (0.87)
      mm Hg (change, -3.7%), mean TC decreased by 90.6 (3.98) mg/dL (change, -27.0%),
      mean LDL-C decreased by 88.9 (3.88) mg/dL (change, -35.6%), and mean TG decreased
      by 26.3 (7.34) mg/dL (change, -15.8%) (all, P < 0.001). Mean HDL-C increased by
      3.6 (1.16) mg/dL (change, 6.9%; P < 0.001). The BP-lowering effect was found only
      in patients with hypertension at baseline (n = 57); in these patients, mean SBP
      decreased by 7.2 (2.44) mm Hg (change, -4.8%; P < 0.005 vs baseline) and DBP
      decreased by 4.8 (1.29) mm Hg (change, -5.6%; P < 0.001 vs baseline). Also in the
      simvastatin group, 26 patients (22.6%) achieved their target SBP/DBP. In patients
      with normotension at baseline (n = 58), neither SBP nor DBP was changed
      significantly (changes, -0.8 [1.65] and -1.4 [1.15] mm Hg, respectively [-0.6%
      and -1.8%, respectively]). The changes in serum lipid levels were similar between
      hypertensive and normotensive patients in the simvastatin group. Forty-one
      patients (18 hypertensive and 23 normotensive at baseline) were treated with
      simvastatin 40 mg/d plus diet between months 3 and 6. At 6 months, no further
      significant decrease was observed in mean BP. In contrast, the expected dose
      dependent response was observed for TC and LDL-C levels. In the diet-only group,
      no significant changes occurred in BP or serum lipid levels. Changes in BP, TC,
      LDL-C, TG, and HDL-C were significantly greater in the simvastatin + diet group
      than in the diet-only group (all, P < 0.001). Body weight did not change
      significantly in either group. CONCLUSIONS: In this group of patients with
      hypercholesterolemia, the starting dosage of simvastatin (20 mg/d) was associated
      with reductions in SBP and DBP within 3 months of treatment in patients with
      hypertension, and this effect was independent of the lipid-lowering properties of
      the drug. Although the decrease in BP was modest, it is likely clinically
      relevant. Further studies on this topic are advisable.

PMID- 24672081
TI  - Efficacy of a novel method of intravenous infusion of the prostaglandin analogue
      iloprost for the treatment of lower-limb critical ischemia: An open-label,
      nonrandomized study in two cohorts.
AB  - BACKGROUND: Patients with advanced peripheral atherosclerotic occlusive disease
      who are no longer candidates for either surgical or intravascular treatment or
      who have undergone unsuccessful surgical revascularization may be treated with IV
      prostanoids. OBJECTIVE: The aim of this study was to assess the efficacy,
      tolerability, compliance, and cost of a new system of prostanoid administration
      that provides a constant plasma concentration of iloprost and maintains the
      efficacy of the drug while reducing the risk for adverse effects (AEs) and the
      overall cost of treatment compared with the actually adopted infusion system.
      METHODS: This open-label, nonrandomized study was conducted at the University
      Hospital of Catania (Catania, Italy). Patients with chronic critical ischemia who
      were not candidates for surgical revascularization were observed. The study
      population was divided into 2 groups: patients in group A were treated with a
      continuous 6-hour IV infusion of iloprost 0.5 to 2.0 ng/kg.min once daily for at
      least 14 consecutive days, and patients in group B were treated with a 20-day
      iloprost continuous IV infusion at a mean dosage of 25 MUg/d by means of a
      portable elastomeric infusion system. Every 5 days the patient was admitted to
      the day-hospital setting to replenish the drug. Primary end points were rates of
      major and minor amputations and death; secondary end points were complete relief
      or a marked reduction of pain at rest, as reflected by discontinuation of
      analgesic therapy and by a decrease in the patients' complaints of pain, as well
      as by the satisfactory healing of ulcerations. Tolerability, compliance, and cost
      also were assessed. RESULTS: Fifty-six patients (34 men, 22 women; mean [SD] age,
      67 [11] years) entered the study. Group A comprised 25 patients; group B, 31
      patients. The rate of major amputation in patients at Fontaine stage IV was
      higher in group A (33.3%) compared with group B (20.0%). The death rate was
      higher in group A (4.0%) than in group B (3.2%). Pain at rest completely subsided
      in 37.5% of patients in group A and 68.8% of patients in group B. Trophic lesions
      healed in 44.4% and 73.3% of patients in groups A and B, respectively. In group
      A, 40.0% of patients experienced AEs (ie, hyperemia, headache, flushing) that
      required a reduction in dose. In group B, 6.5% of patients had hyperemia at the
      injection site that required a reduction in dose. Total cost wasin group B wasd
      ?1995.60, with a mean hospital stay of 6 days. Overall, patients' quality of
      life, assessed as the ability to resume their normal social activities, improved.
      CONCLUSIONS: In this study of patients with chronic lower-limb critical ischemia,
      due to the consistent blood level achieved with iloprost, 20-day iloprost
      continuous IV infusion at a mean dosage of 25 MUg/d administered by means of a
      portable elastomeric infusion system was shown to be similarly or more effective
      than the Methods used by the most important European trials (ie, iloprost 0.5-2.0
      ng/kg.min once daily for at least 14 consecutive days). Furthermore, the patients
      were more compliant and the cost of treatment and the length of hospitalization
      were reduced compared with iloprost 0.5 to 2.0 ng/kg.min once daily for at least
      14 consecutive days.

PMID- 24672082
TI  - Vitamin E treatment in patients with nonalcoholic steatohepatitis: A six-month,
      open-label study of sixteen patients.
AB  - BACKGROUND: Free radicals have a pivotal role in the pathogenesis of nonalcoholic
      steatohepatitis (NASH). Decreasing oxidative stress might have beneficial effects
      on the biochemical and histologic progression of this disease. OBJECTIVE: We
      aimed to determine the therapeutic effect of vitamin E, a potent antioxidant, on
      liver enzymes and histology in NASH. METHODS: This 6-month, open-label study was
      conducted at the Departments of Gastroenterology and Pathology, Gazi University
      School of Medicine (Ankara, Turkey). Patients aged 18 to 70 years with biopsy
      proven NASH were included in the study. All patients received vitamin E 800 U/d
      in 2 divided doses, orally (capsules) for 6 months. Patients were not advised to
      change their exercise or dietary habits. Body mass index (BMI) was calculated at
      months 0 (baseline) and 6. Histologic scoring of steatosis, necroinflammatory
      grade, and fibrosis stage was performed at 0 and 6 months. Liver enzyme
      activities (alanine aminotransferase [ALT], aspartate aminotransferase [AST],
      alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) were monitored
      monthly. Control biopsy specimens were obtained at the end of the treatment. All
      of the liver biopsies were read by a single pathologist (G.A.) who was blinded to
      the clinical, laboratory, and histopathologic data, as well as the sequence of
      liver biopsies. Assessments of compliance and tolerability of treatment were
      performed using a pill count and patient interview, respectively, at the end of
      each month. RESULTS: Sixteen patients (12 men, 4 women; mean [SD] age, 45.5 [6.9]
      years [range, 37-60 years]) were enrolled. All patients completed 6 months of
      treatment. Mean BMI did not change significantly from baseline. Significant
      improvements in mean (SD) serum liver enzyme activities were observed at 6 months
      compared with baseline (ALT: 38.6 [16.3] U/L vs 84.8 [22.1] U/L, respectively, P
      = 0.001; AST: 29.8 [15.4] U/L vs 46.0 [16.0] U/L, respectively, P = 0.001; ALP:
      154.6 [64.1] U/L vs 211.5 [70.4] U/L, respectively, P= 0.011; and GGT: 49.8
      [38.5] U/L vs 64.7 [54.4] U/L, respectively, P = 0.002), as well as in total
      cholesterol level (176.2 [42.0] mg/dL vs 199.6 [60.6] mg/dL; P = 0.02).
      Posttreatment liver biopsy was available in 13 patients (81%). Significant
      improvements in the mean (SD) scores of steatosis (1.46 [0.66] vs 2.43 [0.62]; P
      = 0.002) and necroinflammatory grade (0.84 [0.24] vs 1.31 [0.51]; P= 0.006) were
      observed at 6 months compared with baseline, respectively. However, no
      significant change was noted in the mean (SD) score of fibrosis stage (0.77
      [0.33] vs 1.12 [0.59], respectively). None of the patients reported any adverse
      effects. CONCLUSION: In this small, 6-month, open-label study, vitamin E
      treatment was safe and well tolerated and led to potential biochemical and
      histologic improvements (except in fibrosis) in patients with NASH.

PMID- 24672084
TI  - Corticosteroid-sparing effect of rifaximin, a nonabsorbable oral antibiotic, in
      active ulcerative colitis: Preliminary clinical experience.
AB  - BACKGROUND: The role of enteric flora in the pathogenesis of inflammatory bowel
      disease constitutes the rationale for the use of antibiotics as adjuvant agents
      in the treatment of ulcerative colitis (UC) and Crohn's disease. OBJECTIVE: The
      aim of this study was to assess, in a preliminary fashion, the efficacy of the
      nonabsorbable antibiotic rifaximin in the treatment of exacerbation of UC in
      patients with a history of poor corticosteroid tolerance. METHODS: This open
      label pilot study was conducted in the Gastroenterology Unit, S. Raffaele
      University Hospital (Milan, Italy). Male and female patients aged 18 to 65 years
      with an established diagnosis of left-sided UC who were experiencing a clinical
      relapse during maintenance treatment with mesalamine and with a history of poor
      tolerance to corticosteroid therapy were included in the study. They received
      rifaximin 400 mg BID for 4 weeks while continuing to receive mesalamine 2.4 g/d.
      Disease activity before and after treatment was assessed using Rachmilewitz's
      Activity Index (RAI). A final RAI score <6 was considered clinical remission.
      RESULTS: Ten patients (9 men, 1 woman; mean [sd]age, 48.1 [12.3] years [range, 23
      64 years]) participated in the study. The RAI decreased in all patients.
      Rifaximin treatment induced clinical remission in 7 patients (70%). No adverse
      effects were reported. CONCLUSIONS: Due to our study design, no definitive
      Conclusions can be drawn. However, our preliminary data suggest that rifaximin
      may be beneficial in the treatment of active UC, obviating corticosteroid therapy
      in most cases.

PMID- 24672083
TI  - Effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial
      dysfunction, lipid peroxidation, and hepatocyte morphology in rats with sepsis
      induced liver damage.
AB  - BACKGROUND: Sepsis remains a difficult problem for clinicians, with its systemic
      effects and high morbidity and mortality rates. The roles of oxidative stress,
      endothelial dysfunction, and lipid peroxidation in sepsis-induced organ damage
      are being investigated. OBJECTIVE: The aim of this study was to investigate the
      effects of selective cyclooxygenase (COX)-2 inhibition on tissue lipid
      peroxidation, endothelial dysfunction, and hepatic cell morphology in a rat model
      of sepsis. METHODS: Thirty rats with sepsis induced by cecal ligation and
      puncture were divided equally into 3 groups: treatment group (rofecoxib 1 mg/kg
      PO), control group (saline 1 mL PO), and sham group (sham surgery only). All the
      rats were sacrificed 1 day after sepsis induction. The livers were removed using
      a median laparotomy for histopathologic and biochemical analysis. RESULTS:
      Histomorphologic hepatic damage and lipid peroxidation were significantly reduced
      in the rofecoxib treatment group compared with the control group (P < 0.05 and P
      = 0.001, respectively). Endothelial nitric oxide synthase and inducible nitric
      oxide synthase staining of liver samples was statistically significantly reduced
      in the treatment group compared with the control group (both, P < 0.001). The
      hepatic nitric oxide level and malonyldialdehyde activity decreased significantly
      (P < 0.001 and P = 0.001, respectively) in the rofecoxib group compared with the
      control group. Hepatic myeloperoxidase activity was similar between the treatment
      and control groups. CONCLUSION: Further investigation of selective COX-2
      inhibition as an alternate therapeutic choice for sepsis-induced hepatic damage
      should be considered.

PMID- 24672085
TI  - Optimal compliance in chinese patients (and others).

PMID- 24672086
TI  - Postmarketing surveillance study of benazepril in chinese patients with
      hypertension: An open-label, experimental, epidemiologic study.
AB  - BACKGROUND: Benazepril hydrochloride is an angiotensin-converting enzyme
      inhibitor. Previous clinical trials show that antihypertensive treatment with
      benazepril provides effective blood pressure (BP) control and is generally well
      tolerated by patients with hypertension. However, the long-term antihypertensive
      effects and tolerability of benazepril remain to be established in Chinese
      patients with hypertension. OBJECTIVE: The aim of this study was to investigate
      the long-term efficacy and tolerability of benazepril in Chinese patients with
      essential hypertension. METHODS: This 36-month, community-based, open-label,
      postmarketing surveillance study was conducted in the Nanshi District (Shanghai,
      China). Chinese patients with essential hypertension were to receive 1 or more
      benazepril tablets PO QD in the morning for 36 months. Data for BP and pulse
      pressure (PP) were collected at baseline (month 0) and throughout the
      surveillance period. The rate of patients achieving BP targets (systolic BP
      [SBP]/diastolic BP [DBP], <140/<90 mm Hg) was determined, as was the rate of
      decrease in BP. Subanalyses by sex and age group also were conducted. RESULTS: A
      total of 1831 patients (1090 men, 741 women; mean [SD] age, 55.8 [10.1] years
      [range, 35-88 years]) entered the study. After the 36-month treatment period,
      75.7% of patients receiving benazepril as prescribed (1289 patients) had achieved
      the SBP target, 87.4% achieved the DBP target, and 71.5% achieved both targets.
      After 36 months of treatment, the mean (SD) decreases in SBP, DBP, and PP were
      15.1 (0.4) mm Hg, 11.0 (0.3) mm Hg, and 4.2 (0.4) mm Hg, respectively, among
      compliers. In general, the rate of BP decrease slowed over time. No serious
      adverse drug reactions (ADRs) were detected during the 36-month follow-up period.
      All ADRs except cough (19.9%) occurred at a relatively low incidence rate
      (<3.0%). The cumulative incidence of benazepril related cough was statistically
      significantly higher in women than in men (23.6% vs 18.8%, respectively; P =
      0.007). Of the 1831 patients studied, 1360 patients (74.3%) persisted in taking
      benazepril and were considered optimally compliant at 36-month follow-up.
      CONCLUSION: In this study of Chinese patients with hypertension, benazepril was
      associated with prolonged, stable efficacy in lowering BP and relatively low
      incidence of ADRs.

PMID- 24672087
TI  - Treatment of postoperative emetic symptoms with granisetron in women undergoing
      abdominal hysterectomy: a randomized, double-blind, placebo-controlled, dose
      ranging study.
AB  - BACKGROUND: Postoperative emetic symptoms (nausea, retching, and vomiting)
      frequently occur in women undergoing general anesthesia for abdominal
      hysterectomy. In a previous report by us, granisetron, a selective serotonin
      receptor antagonist, was more effective than the traditional antiemetics,
      droperidol and metoclopramide, for the treatment of postoperative emetic symptoms
      in this population. OBJECTIVE: The aim of this study was to determine the optimal
      dose of granisetron for the treatment of emetic symptoms following abdominal
      hysterectomy. METHODS: This randomized, double-blind, placebo-controlled, dose
      ranging study was conducted at Toride Kyodo General Hospital (Toride, Japan).
      Female patients aged 33 to 66 years experiencing postoperative emetic symptoms
      after abdominal hysterectomy were eligible for the study. Patients received IV
      granisetron at 1 of 4 doses (10, 20, 40, or 100 MUg/kg) or placebo; they were
      then observed for 24 hours. Emetic symptoms and the need for a rescue antiemetic
      were recorded by nursing staff, who were blinded to treatment assignment.
      RESULTS: A total of 100 patients (mean [SD] age, 45 [7] years [range, 33-66
      years]) were enrolled (n = 20 in each group). No significant differences in
      patient demographic characteristics were observed between the groups. The number
      of patients in whom complete control of postoperative emetic symptoms, defined as
      being free of emetic symptoms and not needing rescue antiemetic medication for 24
      hours after study drug administration, was established was significantly greater
      in 3 of the granisetron groups than in the placebo group (6 patients [30%]):
      granisetron 10 MUg/kg, 7 patients (35%; P= NS); granisetron 20 MUg/kg, 17
      patients (85%; P = 0.001); granisetron 40 MUg/kg, 17 patients (85%; P = 0.001);
      and granisetron 100 MUg/kg, 16 patients (80%; P = 0.002). No clinically
      significant adverse events attributable to the study drug were observed in any
      group. CONCLUSION: In this study of patients who experienced emetic symptoms
      after undergoing general anesthesia for abdominal hysterectomy, granisetron at
      doses >=20 MUg/kg was effective in the treatment of established postoperative
      emetic symptoms.

PMID- 24672088
TI  - Metabolic effects of fluvastatin extended release 80 mg and atorvastatin 20 mg in
      patients with type 2 diabetes mellitus and low serum high-density lipoprotein
      cholesterol levels: a 4-month, prospective, open-label, randomized, blinded-end
      point (probe) trial.
AB  - BACKGROUND: Diabetic dyslipidemia is characterized by greater triglyceridation of
      all lipoproteins and low levels of plasma high-density lipoprotein cholesterol
      (HDL-C). In this condition, the serum level of low-density lipoprotein
      cholesterol (LDL-C) is only slightly elevated. The central role of decreased
      serum HDL-C level in diabetic cardiovascular disease has prompted the
      establishment of a target of >=50 mg/dL in patients with diabetes mellitus (DM).
      OBJECTIVE: The aim of the study was to assess the effects of once-daily
      administration of fluvastatin extended release (XL) 80 mg or atorvastatin 20 mg
      on serum HDL-C levels in patients with type 2 DM and low levels of serum HDL-C.
      METHODS: This 4-month, prospective, open-label, randomized, blinded-end point
      (PROBE) trial was conducted at Endocrinology and Diabetology Service, L. Sacco
      Polo University Hospital (Milan, Italy). Patients aged 45 to 71 years with type 2
      DM receiving standard oral antidiabetic therapy, with serum HDL-C levels <50
      mg/dL, and with moderately high serum levels of LDL-C and triglycerides (TG) were
      enrolled. After 1 month of lifestyle modification and dietary intervention,
      patients who were still showing a decreased HDL-C level were randomized, using a
      1:1 ratio, to receive fluvastatin XL 80-mg tablets or atorvastatin 20-mg tablets,
      for 3 months. Lipoprotein metabolism was assessed by measuring serum levels of
      LDL-C, HDL-C, TG, apolipoprotein (apo) A-I (the lipoprotein that carries HDL),
      and apo B (the lipoprotein that binds very low-density lipoprotein cholesterol,
      intermediate-density lipoprotein, and LDL on a molar basis). Patients were
      assessed every 2 weeks for treatment compliance and subjective adverse events.
      Serum creatine phosphokinase and liver enzymes were assessed before the run-in
      period, at the start of the trial, and at 1 and 3 months during the study.
      RESULTS: One hundred patients were enrolled (50 patients per treatment group;
      fluvastatin XL group: 33 men, 17 women; mean [SD] age, 58 [12] years;
      atorvastatin group: 39 men, 11 women; mean [SD] age, 59 [11] years). In the
      fluvastatin group after 3 months of treatment, mean (SD) LDL-C decreased from 149
      (33) to 95 (25) mg/dL (36%; P < 0.01), TG decreased from 437 (287) to 261 (164)
      mg/dL (40%; P < 0.01), and HDL-C increased from 41 (7) to 46 (10) mg/dL (12%; P <
      0.05). In addition, apo A-I increased from 118 (18) to 124 (15) mg/dL (5%; P <
      0.05) and apo B decreased from 139 (27) to 97 (19) mg/dL (30%; P < 0.05). In the
      atorvastatin group, LDL-C decreased from 141 (25) to 84 (23) mg/dL (40%; P <
      0.01) and TG decreased from 411 (271) to 221 (87) mg/dL (46%; P < 0.01). Neither
      HDL-C (41 [7] vs 40 [6] mg/dL; 2%) nor apo A-I (117 [19] vs 114 [19] mg/dL; 3%)
      changed significantly. However, apo B decreased significantly, from 131 (20) to
      92 (17) mg/dL (30%; P < 0.05). Mean changes in HDL-C (+5 [8] vs -1 [2] mg/dL; P <
      0.01) and apo A-I (+6 [18] mg/dL vs -3 [21] mg/dL; P < 0.01) were significantly
      greater in the fluvastatin group than in the atorvastatin group, respectively.
      However, the decreases in LDL-C (54 [31] vs 57 [32] mg/ dL), TG (177 [219] vs 190
      [65] mg/dL), and apo B (42 [26] vs 39 [14] mg/dL) were not significantly
      different between the fluvastatin and atorvastatin groups, respectively. No
      severe adverse events were reported. CONCLUSIONS: Fluvastatin XL 80 mg and
      atorvastatin 20 mg achieved mean serum LDL-C (<= 100 mg/dL) and apo B target
      levels (<= 100 mg/dL) in the majority of this population of patients with type 2
      DM, but mean serum HDL-C level was increased significantly only with fluvastatin
      16 patients (32%) in the fluvastatin group compared with none in the atorvastatin
      group achieved HDL-C levels >=50 mg/dL. The increase in HDL-C in the fluvastatin
      treated patients was associated with an increase in apo A-I, suggesting a
      potential pleiotropic and selective effect in patients with low HDL-C levels.

PMID- 24672089
TI  - Chemopreventive effect of nonsteroidal anti-inflammatory drugs on the development
      of a new colorectal polyp or adenoma in a high-risk population: a meta-analysis.
AB  - BACKGROUND: Although many experimental, epidemiologic, and clinical studies have
      suggested that aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) are
      effective in reducing and preventing colorectal adenomas, randomized, controlled
      trials (RCTs) are still being carried out to obtain statistically reliable
      results. OBJECTIVE: The aim of this meta-analysis was to review long-term,
      prospective RCTs investigating the effect of NSAIDs on the relative risk (RR) for
      developing >=1 new colorectal polyp or adenoma in a high-risk population.
      METHODS: We conducted a comprehensive search of MEDLINE, PubMed, and other
      electronic databases (including Inter-Science, Science Direct, Ebsco, Synergy,
      and Proquest) (key terms: nonsteroidal anti-inflammatory drugs, aspirin,
      colorectal, and polyps; years: 1974-2004) for English-language articles. Eligible
      studies were analyzed in terms of demographic data, adverse effects, and effect
      of NSAIDs on the RRs. RESULTS: Four long-term, prospective RCTs were used in the
      statistical analysis. A total of 2069 high-risk patients were enrolled; 1880
      patients completed the studies, and 1127 were in active-treatment groups (aspirin
      81-325 mg/d or sulindac 150-300 mg/d). Our meta-analysis of these studies
      revealed that the overall RR for developing >= 1 new colorectal polyp or adenoma
      was significantly reduced by using aspirin or other NSAIDs (RR = 0.809; 95% CI,
      0.718-0.912). CONCLUSIONS: The results of this meta-analysis suggest that regular
      use of aspirin 81 to 325 mg/d or sulindac 150 to 300 mg/d for >=1 year was
      associated with a decrease in the RR for developing >= 1 new colorectal polyp or
      adenoma to 0.80 (95% CI, 0.718-0.912) in patients at high risk.

PMID- 24672090
TI  - Early migraine intervention with sumatriptan 100 mg in patients with a history of
      nonresponse to sumatriptan 50 mg: an open-label, prospective study of multiple
      attacks.
AB  - BACKGROUND: Early treatment with sumatriptan tablets (50 and 100 mg) has been
      shown to be effective in retrospective and prospective study designs. Despite the
      efficacy of sumatriptan 50 mg and early intervention, however, some patients
      continue not to respond completely to this dose. New evidence with a scientific
      basis for early intervention suggests that some patients may need to treat early
      to prevent the establishment of central sensitization. Also, patients cite
      complete pain relief as the most important attribute of a migraine medication.
      OBJECTIVE: The primary objective of this study was to determine the 2-hour
      efficacy of sumatriptan 100 mg in achieving complete pain relief in patients with
      a history of nonresponse to sumatriptan 50 mg in an early-intervention treatment
      paradigm. Secondary end points included complete pain relief at 4 hours,
      consistency of complete relief in at least 2 of 3 attacks, sustained complete
      relief over 24 hours, satisfaction with the 100-mg dose, and relief of associated
      symptoms. METHODS: This open-label, prospective study was conducted at the Wesley
      Headache Clinic (Memphis, Tennessee). Male and female patients between the ages
      of 18 and 65 years who fulfilled International Headache Society classification
      criteria for migraine, and who had a documented history of nonresponse to
      sumatriptan 50 mg at 2 hours after dosing when treating in the early, mild-pain
      phase in at least 2 of 3 migraine attacks were eligible for the study. Patients
      were instructed to receive one 100-mg sumatriptan tablet at the earliest sign of
      pain, while still mild, in 3 subsequent migraine attacks. After each treated
      attack, patients were to record a detailed diary entry. RESULTS: Twenty patients
      (17 women, 3 men; mean age, 44 years) treated all 3 migraines during the early,
      mild-pain phase and completed the study. Of the 60 attacks treated, 48 (80%) were
      pain free at 2 hours, 56 (93%) were pain free at 4 hours, and 45 (75%) were pain
      free at 2 hours and continued to be pain free at 24 hours (sustained pain-free
      response). Sumatriptan 100 mg was well tolerated; none of the patients reported
      any adverse events. CONCLUSIONS: In this study of migraineurs with a history of
      nonresponse to sumatriptan 50 mg at 2 hours after dosing in the early, mild-pain
      phase of migraine, increasing the dose of sumatriptan from 50 mg to 100 mg in the
      early-intervention paradigm, in most attacks complete pain relief was achieved
      for up to 24 hours. Because patients have indicated that becoming pain free was
      their therapeutic goal, based on the results of this study, physicians may want
      to consider increasing the dose of sumatriptan to 100 mg at the first sign of
      pain if the patient has consistently not responded to sumatriptan 50 mg in the
      early-intervention model.

PMID- 24672091
TI  - Comparison of benzydamine hydrochloride and Salvia officinalis as an adjuvant
      local treatment to systemic nonsteroidal anti-inflammatory drug in controlling
      pain after tonsillectomy, adenoidectomy, or both: an open-label, single-blind,
      randomized clinical trial.
AB  - BACKGROUND: Benzydamine hydrochloride (BNZD) is a nonsteroidal anti-inflammatory
      drug (NSAID) used in an oral rinse formulation as an adjuvant to other NSAIDs in
      controlling postoperative pain after tonsillectomy, adenoidectomy, or both.
      Salvia officinalis (SO) is a topically applied herbal preparation frequently used
      for the same indication. Pain, bleeding, and infection are the most common
      postoperative complications of tonsillectomy. OBJECTIVE: The aim of this study
      was to compare the efficacy and tolerability of BNDZ with those of SO as adjuvant
      treatments in controlling postoperative pain. METHODS: This open-label, single
      blind, randomized clinical trial was conducted at the Department of
      Otorhinolaryngology, Clinical Hospital Center "Dr. Dragisa Misovic-Dedinje"
      (Belgrade, Serbia and Montenegro). Pediatric and adult patients undergoing
      tonsillectomy, adenoidectomy, or both were enrolled. Patients were randomized to
      receive BNZD or SO, in addition to ibuprofen 20 mg/kg.d (children) or diclofenac
      100 mg/d (adults). The primary end point was the proportion of patients with mild
      or no pain on postoperative days 1, 2, 4, and 7. Secondary end points were the
      incidences of infection, hemorrhage, and other adverse events. RESULTS: A total
      of 420 patients were enrolled (217 females, 203 males; 278 children, 142 adults;
      mean [SD] age, 6.2 [2.1] years [children] and 24.1 [9.8] years [adults] [range, 3
      45 years]). One hundred thirty-eight children received BNZD; 140 received SO
      (both in addition to ibuprofen 20 mg/kg.d). Seventy-two adults received BNZD; 70
      received SO (both in addition to diclofenac 100 mg/d). A significantly lower
      proportion of children treated with adjuvant BNZD experienced moderate or severe
      pain than those treated with SO at each time point (P < 0.01 at days 1 and 4; P <
      0.001 at days 2 and 7). In children, the risk for postoperative infection was
      similar between BNZD and SO (absolute risk reduction [ARR], 6.9%; 95% CI, 6.4%
      7.6%); however, the risk was reduced in adults (ARR, 19.0%; 95% CI, 16.5%-21.9%;
      P = 0.008). CONCLUSIONS: In this clinical trial of children and adults who
      underwent tonsillectomy, adenoidectomy, or both, BNZD, as an adjuvant to an
      NSAID, was more effective than SO in controlling postoperative pain and
      infection. The pain-reducing effect of BNZD was of quick onset and persisted for
      1 week after surgery. The safety profile of BNZD was comparable to that of SO,
      with the exception of postoperative infection in adults, for which BNZD was more
      efficacious. In particular, the use of BNZD was not associated with a high risk
      for early postoperative hemorrhage.

PMID- 24672092
TI  - Effects of cimetidine, a histamine type 2 receptor antagonist, on
      microcirculatory disturbance of the stomach induced by full-thickness burn
      injuries as a model for surgical stress in rats.
AB  - BACKGROUND: We have reported the preventive effect of cimetidine, a histamine
      type 2 receptor antagonist, on decreased gastric mucosal blood flow induced by
      burn injury, a model of surgical stress. OBJECTIVE: The present study was
      performed to assess the effects of cimetidine on gastric microcirculatory
      disturbance induced by surgical stress. METHODS: Twelve male Wistar rats were
      anesthetized and a 30% full-thickness dorsal scald burn was inflicted. The total
      lengths of gastric erosions were measured using stereoscopic microscopy.
      Microvascular images in the basal region of the gastric mucosa were observed
      using an intravital microscope, and the diameters of venules and collecting
      venules were measured. Rolling leukocytes inside and along the venules, an
      indication of endothelial damage to the microcirculation, were observed. The rats
      were assigned to the cimetidine group or the control group (both, n = 6).
      Cimetidine 100 mg/kg was administered 30 minutes before and 2.5 hours after
      infliction of the burn injury. Animals in the control group were given only
      isotonic saline. Values are expressed as mean (SD). RESULTS: Contraction of
      venules was easily observed in all rats in the control group. However, venular
      contraction was rarely observed in the cimetidine group. The total length of
      gastric erosions was significantly decreased in the cimetidine group compared
      with the control group (0.93 [0.58] MUm vs 5.98 [5.18] MUm, respectively; P <
      0.05). The percentages of rolling leukocytes that passed the confluence of a
      prevenule and a venule were also significantly decreased in the cimetidine group
      compared with the control group (4.7% [7.3%] vs 22.6% [5.7%]; P < 0.01). The
      diameters of the venules and collecting venules were significantly larger in the
      cimetidine group (57.3 [6.8] MUm and 75.9 [3.6] MUm, respectively) than in the
      control group (30.9 [9.2] MUm and 46.8 [8.0] MUm, respectively) (both, P < 0.01).
      CONCLUSIONS: The present study suggests that cimetidine may have a protective
      effect against gastric microcirculatory disturbances induced by burn injury, a
      model of surgical stress.

PMID- 24672093
TI  - Comparison of the effects of parecoxib and diclofenac in preemptive analgesia: A
      prospective, randomized, assessor-blind, single-dose, parallel-group study in
      patients undergoing elective general surgery.
AB  - BACKGROUND: Preoperative administration of analgesics may prevent or
      reducehyperalgesia, inhibit inflammation, and reduce pain by reducing the
      synthesis of prostaglandins in response to tissue damage caused by surgery.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potent, widely used class of
      analgesic agents; however, they may not be as effective as selective
      cyclooxygenase (COX)-2 inhibitors. OBJECTIVE: The aim of this study was to
      compare the efficacy and tolerabilityof the COX-2 inhibitor parecoxib sodium and
      the NSAID diclofenac sodium as preemptive analgesics in patients undergoing
      elective general surgery. METHODS: This was a prospective, randomized, assessor
      blind, single-dose,parallel-group, comparative trial. Patients aged 18 to 65
      years undergoing elective general surgery were enrolled. A single IM injection of
      parecoxib 40 mg or diclofenac 75 mg was administered 30 to 45 minutes before the
      induction of anesthesia. Surgery was performed as per standard protocol. The
      primary measures of efficacy were pain intensity score (measured on a visual
      analog scale [VAS]), pain relief score, duration of analgesia, and platelet
      aggregation response to adenosine diphosphate. Tolerability assessment included
      monitoring of treatment-emergent adverse events (AEs), physical examination,
      laboratory analysis, electrocardiography, and chest radiography. RESULTS: Eighty
      patients (56 men, 24 women; mean [SD] age, 45.96 [12.83] years) were enrolled in
      the study (40 patients per treatment group). All patients completed the trial. No
      pain was reported by any patient in the parecoxib group up to 12 hours; in the
      diclofenac group, no pain was reported up to 6 hours. At 12 hours, the mean (SD)
      VAS score was 2.33 (1.39) (moderate pain) in the diclofenac group and 0 (no pain)
      in the parecoxib group (P < 0.05). At 12 hours, total pain relief was reported by
      all 40 patients (100.0%) in the parecoxib group but by none (0.0%) in the
      diclofenac group, and 2 patients in the diclofenac group (5.0%) reported good
      pain relief (between-group difference for total + good pain relief, P < 0.05).
      Mean (SD) duration of analgesia was significantly longer in the parecoxib group
      than in the diclofenac group (19.48 [5.61] hours vs 8.32 [4.11 ] hours; P <
      0.05). Platelet aggregation was significantly inhibited in the diclofenac group
      (change from baseline, 64.0%) but not in the parecoxib group (change from
      baseline, 12.0%) (P < 0.05). Both regimens were well tolerated, and no AEs were
      reported. CONCLUSIONS: In this study of patients undergoing elective general
      surgery,patients treated with the COX-2 specific inhibitor parecoxib experienced
      no pain at 12 hours, and the treatment was well tolerated. The results of this
      study suggest that good postoperative analgesia and minimal interference with
      platelet function may make parecoxib an alternative to the nonselective NSAID
      diclofenac in providing preemptive analgesia in patients undergoing general
      surgery.

PMID- 24672094
TI  - Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant
      or nonresponsive to previous lactulose treatment: An open-label, pilot study.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome
      that occurs in patients with advanced hepatic disease. One of the main pathogenic
      mechanisms is represented by circulating toxins produced by the intestinal
      metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly
      based on drugs that eliminate ammonia-producing bacteria. OBJECTIVES: The aim of
      this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin
      in patients with HE who were intolerant or nonresponsive to treatment with an
      oral, nonabsorbable disaccharide (lactulose). METHODS: This uncontrolled, open
      label, pilot study was conducted at the University of Bologna, Bologna, Italy.
      Patients aged >= 18 years with histologically proven liver cirrhosis and HE were
      studied. All patients were intolerant or nonresponsive to previous treatment with
      lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg
      TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at
      enrollment and at the end of the treatment period. Tolerability was assessed
      using hematology, biochemistry, and urinalysis and by recording adverse effects
      (AEs). RESULTS: Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0]
      years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients
      completed the study. Significant improvement was shown in most of the 5
      components of the PSE index after rifaximin administration in both intolerants
      and nonresponders. At the end of the 10-day treatment period, the PSE index was
      significantly reduced in both intolerants and nonresponders. Rifaximin was well
      tolerated; no clinically relevant AEs were observed during the treatment period.
      CONCLUSIONS: This pilot study of patients with liver cirrhosis and HE who were
      intolerant or nonresponsive to previous treatment with an oral, nonabsorbable
      disaccharide suggests that treatment with rifaximin may be considered as an
      adjuvant or an alternative treatment in reducing HE.

PMID- 24672096
TI  - Publisher's announcement.

PMID- 24672095
TI  - Phenotypic and genotypic characterization of invasive Streptococcus pneumoniae
      clinical isolates.
AB  - BACKGROUND: The emergence of infection caused by invasive
      penicillinnonsusceptible (PNS) and multidrug-resistant strains of Streptococcus
      pneumoniae has become a worldwide concern, necessitating the epidemiologic
      surveillance of such strains. OBJECTIVES: One aim of this study was to identify
      clones of invasive PNS S pneumoniae among isolates in Riyadh, Saudi Arabia. The
      second aim was to compare these clones with international clones to track their
      spread in Saudi Arabia. METHODS: The phenotypes of invasive isolates
      characterized as S pneumoniae were determined using susceptibility testing and
      serotyping (capsular test and E-test). The genotypes of PNS isolates were
      determined using random amplified polymorphic DNA analysis. The genetic
      relatedness of these local strains to the international widespread clones was
      investigated. RESULTS: Of 296 S pneumoniae isolates identified using biochemical
      and culture characteristics, 89 (30.1%) were invasive. Susceptibility testing
      using the E-test revealed that 17 of the 89 invasive isolates (19.1%) were PNS.
      Most of the 89 isolates (89.9%) were resistant to sulfamethoxazole-trimethoprim;
      32.6% and 23.6% of isolates were resistant to chloramphenicol and tetracycline,
      respectively. All of the isolates (100.0%) were fully susceptible to ceftriaxone
      and vancomycin. Capsular serotyping of the 89 isolates showed that 19A (18.0%),
      613 (14.6%), 23F (13.5%), 9V (11.2%), 14 (6.7%), 19F (5.6%), and 18C (4.5%) were
      the most predominant serogroups/serotypes. The 17 PNS strains were confirmed on
      polymerase chain reaction to have penicillin resistance genes. Of these 17
      strains, international clone 19A-a was the most predominant (41.2%), followed by
      6B-a (17.6%), and 23F-a and 9V-a (each, 11.8%). CONCLUSIONS: The present study
      identified the spread of the 4 most commonPNS S pneumoniae isolates (clones)-19A,
      613, 23F, and 9V-to Riyadh, but identified no new clones among patients having
      invasive infection with S pneumoniae in Riyadh. This study emphasizes that
      international PNS clones have contributed to the prevalence and spread of PNS
      pneumococci among the clinical isolates in Saudi Arabia.

PMID- 24672097
TI  - Comparison of the effects of bimatoprost and timolol on intraocular pressure and
      pulsatile ocular blood flow in patients with primary open-angle glaucoma: A
      prospective, open-label, randomized, two-arm, parallel-group study.
AB  - Abstract. BACKGROUND: The current objective of antiglaucomatous therapy is to
      reduce intraocular pressure (IOP), and thus to preserve visual function. Many
      ophthalmologists believe this objective is best achieved by methods that improve
      ocular blood flow to the optic nerve head. Beta-blockers are effective ocular
      hypotensive agents, but they can reduce choroidal blood flow. Bimatoprost, a new
      prostamide analogue, has been shown to have a better IOP-lowering effect compared
      with the nonselective beta-adrenergic receptor blocker timolol maleate, but
      little is known about its effects on the vascular bed of the eye. OBJECTIVE: The
      aim of this study was to compare the effects of bimatoprost and timolol on IOP
      and choroidal blood flow (as measured using pulsatile ocular blood flow [pOBF])
      in patients with primary open-angle glaucoma (POAG). METHODS: This prospective,
      open-label, randomized, 2-arm, parallel-group study was conducted at the Glaucoma
      Research Centre, Department of Ophthalmology, University Hospital of Bari, Bari,
      Italy. Patients with POAG having well-controlled IOP (<16 mm Hg) on monotherapy
      with timolol 0.5% ophthalmic solution (2 drops per affected eye BID) for >=12
      months but with a progressive decrease in pOBF during the same time period were
      randomly allocated to 1 of 2 treatment groups. One group continued monotherapy
      with timolol, 2 drops per affected eye BID. The other group was switched (without
      washout) to bimatoprost 0.3% ophthalmic solution (2 drops per affected eye QD [9
      pm]). Treatment was given for 180 days. IOP and pOBF were assessed at the
      diagnostic visit (pre-timolol), baseline (day 0), and treatment days 15, 30, 60,
      90, and 180. Primary adverse effects (AEs) (ie, conjunctival hyperemia,
      conjunctival papillae, stinging, burning, foreign body sensation, and
      pigmentation of periorbital skin) were monitored throughout the study. RESULTS:
      Thirty-eight patients were enrolled (22 men, 16 women; mean [SD] age, 51.7 [4.8]
      years; 19 patients per treatment group; 38 eligible eyes). At 180-day follow-up
      in the timolol group, the IOP and the pOBF remained unchanged compared with
      baseline. In the bimatoprost group the IOP remained unchanged and the pOBF was
      decreased by 38.9% compared with baseline (P < 0.01). All AEs were mild to
      moderate and included conjunctival hyperemia and ocular itching (5 patients
      [26.3%] in the bimatoprost group) and pigmentation of periorbital skin (2
      patients [40.0%] in the bimatoprost group). The incidence of each AE was higher
      in the bimatoprost group than in the timolol group (P = 0.008). CONCLUSIONS: In
      this population of patients with POAG, bimatoprost was associated with increased
      pOBF, and the reduction in pOBF associated with timolol was corrected after
      patients were switched to bimatoprost. Bimatoprost was associated with increased
      choroidal blood flow, beyond the levels recorded before timolol treatment. The
      decreased IOP level achieved in the timolol group seemed to be improved further
      by bimatoprost. Considering the potential efficacy of bimatoprost on IOP and
      pOBF, we suggest that this new drug may represent a clinical advance in the
      medical treatment of POAG.

PMID- 24672098
TI  - An open-label comparison of the effects of simvastatin and niacin alone and
      combined on the lipid profile and lipoprotein (a) level in an Indian population
      with dyslipidemia.
AB  - Abstract. BACKGROUND: Patients with dyslipidemia often require the use of >1
      lipid-altering agent to achieve the target levels recommended by the National
      Cholesterol Education Program Adult Treatment Panel III. OBJECTIVE: The aim of
      this study was to compare the effects of simvastatin and niacin alone and
      combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian
      population with dyslipidemia. METHODS: This 12-week, open-label, nonrandomized
      study was conducted at the Departments of Pharmacology and Medicine, Government
      Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with
      dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups.
      Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at
      doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks.
      Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg
      for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C],
      high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and
      triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6
      and 12 weeks of treatment. Percentage changes from baseline were calculated.
      Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous
      reporting. RESULTS: Ninety patients were enrolled (50 men, 40 women; 30 patients
      per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C
      level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was
      seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were
      18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P <
      0.05), but no significant change was seen in group 1. TC levels decreased by a
      mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was
      seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of
      the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs
      in patients receiving niacin. CONCLUSIONS: In this study in Indian patients with
      dyslipidemia, simvastatin-niacin combination therapy was associated with greater
      changes in lipid profile compared with either agent used alone. Niacin was also
      associated with greater changes in Lp(a) levels. AEs were less prevalent with
      combination therapy than with niacin alone.

PMID- 24672099
TI  - Observational study of compliance and continuance rates of raloxifene in the
      prevention and treatment of osteoporosis.
AB  - Abstract. BACKGROUND: Medical practitioners face the challenge of noncompliance
      with prescriptions, particularly in chronic, asymptomatic, diseases such as
      osteoporosis. OBJECTIVE: The aim of this study was to assess the raloxifene
      compliance and continuance rates and adverse effects over 24 months in clinical
      practice. METHODS: Using a retrospective study of clinical histories obtained
      from a database at the Metabolic Research Institute, University of El Salvador
      School of Medicine, Buenos Aires, Argentina, as well as telephone interviews, we
      assessed compliance and continuance with raloxifene therapy in post-menopausal
      patients who had received prescriptions for raloxifene to prevent or treat
      osteoporosis. Patients were contacted by telephone 24 months after they had
      received a prescription for raloxifene. Compliance and continuance rates were
      calculated based on the data provided by the patients. RESULTS: Data from 419
      patients (mean [SD] age, 61.4 [7.4] years [range, 42-90 years]) were included in
      the study. At the time of the telephone interview, 225 (53.7%) were still
      receiving raloxifene, 105 (25.1%) had stopped treatment at their own discretion,
      59 (14.1%) had not started treatment, and 30 (7.2%) had discontinued treatment as
      a result of advice from a physician. The reasons for not starting treatment were
      fear of thrombolytic events (21 patients [35.6%]); lack of interest in starting
      treatment (12 [20.3%]); other physician's advice (11 [18.6%]); family problems (3
      [5.1%]); dissatisfaction with the prescribing physician, treatment cost, health
      problems unrelated to osteoporosis, and mistrust in the prescription (each, 2
      [3.4%]); and advice from family/friends, fear of breast cancer, belief that
      raloxifene is hormonal, and that the patient was already polymedicated (each, 1
      [1.7%]). Eleven of the 59 patients (18.6%) who had not started therapy were
      advised by a physician other than the prescribing physician not to start
      treatment and were excluded from the compliance analysis. Thus, the compliance
      analysis included 408 patients. The 2 most common reasons for discontinuing
      treatment at the patient's own discretion were health problems unrelated to
      osteoporosis (25 [23.8%]) and digestive problems not considered treatment related
      (16 [15.2%]). The compliance rates were 75.0%, 71.1%, 65.0%, 57.1%, and 52.0% at
      3, 6, 12, 18, and 24 months, respectively. In patients who started raloxifene
      treatment, the continuance rates were 85.0%, 80.6%, 73.6%, 64.7%, and 58.9% at 3,
      6, 12, 18, and 24 months, respectively. Sixty-two of the 135 patients who
      discontinued treatment did so within 3 months of receiving the prescription,
      accounting for 45.9% of all discontinuations. CONCLUSIONS: In the present study
      of raloxifene compliance and continuance in clinical practice, the compliance
      rate appeared to be relatively high compared with those of hormone-replacement
      therapy (HRT) and other non-HRT treatments. Almost half of patients who
      discontinued treatment did so in the first 3 months.

PMID- 24672100
TI  - Complementary and alternative medicine use by patients visiting a free health
      clinic: A single-site, pilot study.
AB  - BACKGROUND: The rate of use of complementary and alternative medicine (CAM) has
      been documented to fluctuate widely, can greatly impact medical outcomes, and can
      influence patients' adherence to conventional medicines. Health care providers
      should assess the prevalence of CAM use (primarily herbal medicine) in individual
      settings to most accurately provide appropriate patient care. OBJECTIVES: THE AIM
      OF THIS STUDY WAS TO DETERMINE THE FOLLOWING: (1) differences in demographic
      characteristics between users and nonusers of CAM; (2) which CAM patients are
      using; (3) patients' sources of information concerning CAM; and (4) whether
      patients recall being asked about CAM use by their health care providers.
      METHODS: In this single-center, pilot study, a self-administered survey
      concerning CAM use was made available to persons seeking care at an inner-city
      free health clinic (Kansas City Free Health Clinic, Kansas City, Missouri).
      Completed surveys were scanned into a database, and descriptive analyses were
      performed. RESULTS: Three hundred eleven patients completed >=1 question on the
      survey. Of those who reported race (n = 278), 168 (60.4%) were Caucasian/white,
      73 (26.3%) were African American/black, and 24 (8.6%) were Hispanic/Latino. Of
      those who reported educational level (n = 287), 101 (35.2%) had some high school
      or were high school graduates or had a general equivalency development diploma,
      102 (35.5%) had completed some college or vocational training, and 84 (29.3%) had
      completed college. Of those who reported personal annual income (n = 191), 107
      (56.0%) reported up to US $15,000, and 54 (28.3%) reported >$15,000 to $30,000. A
      high rate of CAM use (past or present) was found among survey respondents
      (116/285 [40.7%]). No correlation was found between CAM use and any of the
      demographic characteristics studied. Of 98 patients reporting whether their CAM
      use was past or current, 64 (65.3%) were using CAM at the time of the survey.
      Friends and physicians were reported to be most supportive of CAM use (21/41
      [51.2%] and 33/86 [38.4%] patients, respectively). The most common CAM products
      reported as being currently used were garlic and chamomile (both, 5 patients
      [7.1%]), and echinacea and ginseng (both, 3 patients [4.7%]). CONCLUSION: This
      survey of patients using an inner-city free health clinic showed a high rate of
      CAM use, which could significantly impact patient outcomes.

PMID- 24672101
TI  - Efficacy of concomitant administration of clarithromycin and acetylcysteine in
      bronchiolitis obliterans in seventeen sulfur mustard-exposed patients: An open
      label study.
AB  - BACKGROUND: Victims of sulfur mustard (SM) gas exposure experience different
      types of chronic pulmonary disease, manifested as cough, sputum production, and
      dyspnea. Conventional therapies (eg, immunosuppressive drugs, corticosteroids)
      have not been effective in these patients. OBJECTIVE: This study was carried out
      to determine the efficacy of concomitant administration of the macrolide
      clarithromycin and the mucolytic agent acetylcysteine in the treatment of
      bronchiolitis obliterans in SM-exposed patients. METHODS: This open-label
      clinical study was conducted at the Research Center of Chemical Injuries,
      Baqiyatallah Medical Sciences University, Tehran, Iran. Clarithromycin and
      acetylcysteine were administered concomitantly for 6 months to male SM-exposed
      patients with chronic bronchitis and bronchiolitis obliterans who were
      nonresponsive to conventional treatments. Efficacy analysis included symptom
      assessment and pulmonary function tests (forced expiratory volume in 1 second
      [FEV1], forced vital capacity [FVC], and FEV1/FVC ratio) using spirometry,
      performed at baseline and after 2 and 6 months of treatment. RESULTS: Seventeen
      male patients (mean [SD] age, 38.3 [5.3] years [range, 31-50 years]; mean [SD]
      body weight, 77.9 [15.7] kg) were included in the study. Cough and sputum
      production were each found in 10 of 17 patients (58.8%) at baseline and were
      improved in all 10 patients after the administration of clarithromycin and
      acetylcysteine. FEV1 and FVC also were improved, by mean (SD) 10.6% (9.7%) (P <
      0.001 vs baseline) and 12.9% (13.6%) (P = 0.001 vs baseline). No significant
      change in FEV1/FVC ratio was found. CONCLUSIONS: In this study of concomitant
      administration of clarithromycin and acetylcysteine for the treatment of
      bronchiolitis obliterans in SM-exposed patients, symptoms and pulmonary function
      were improved. These results may have been related to the therapeutic effects of
      a macrolide antibiotic on chronic bronchitis and bronchiolitis obliterans in
      these patients. Based on the results of this study, we recommend this treatment
      for chemical warfare victims with recurrent exacerbation of bronchitis who do not
      respond to conventional treatment.

PMID- 24672105
TI  - Publisher's announcement.

PMID- 24672102
TI  - Effects of D-004, a lipid extract from Cuban royal palm fruit, on inhibiting
      prostatic hypertrophy induced with testosterone or dihydrotestosterone in a rat
      model: A randomized, controlled study.
AB  - BACKGROUND: Benign prostatic hypertrophy is the nonmalignant, uncontrolled growth
      of prostatic epithelial cells and stroma that, left untreated, may lead to
      difficult urination and other complications. A common treatment of BPH is lipid
      extract from saw palmetto fruit, and lipid extract from Cuban Royal palm (a palm
      of the same family) fruit is being studied for this use. One study found that the
      latter, D-004, at 100 to 400 mg/kg daily prevented prostatic hypertrophy (PH)
      induced with testosterone (T) in a rat model. OBJECTIVES: This study comprised 2
      experiments in a rat model. The first assessed the effects of different doses of
      D-004 on T-induced PH; the second investigated the effects of D-004 on PH induced
      with dihydrotestosterone (DHT). METHODS: In experiment 1, rats were distributed
      in 6 groups of 10 rats each. One group received an SC injection of soy oil and
      oral treatment with Tween 65/water vehicle (negative control). The other 5 groups
      received an SC injection of T 3 mg/kg daily and oral treatment with vehicle
      (positive control) or D-004 at 50, 200, 400, or 800 mg/kg daily suspended in
      vehicle. In experiment 2, rats were distributed in 3 groups of 10 rats each. A
      negative control group received treatment as in experiment 1. Positive controls
      received an SC injection of DHT 1.5 mg/kg and vehicle orally. The third group
      received an SC injection of DHT and oral treatment with D-004 at 800 mg/kg
      suspended in vehicle. All treatments were given for 14 days. At sacrifice,
      prostates were removed and weighed. Mean prostatic weights and prostatic/body
      weight ratios were calculated. RESULTS: In experiment 1, in the groups receiving
      D-004 at 200, 400, or 800 mg/kg daily, prostatic weight was significantly lower
      compared with the positive control group (P < 0.05, P < 0.01, and P < 0.001,
      respectively); this effect was not seen in the group receiving 50 mg/kg daily. In
      the groups receiving D-004 at 400 and 800 mg/kg daily, prostatic/body weight
      ratio was significantly lower compared with positive controls (both, P < 0.05);
      this effect was not seen in the groups receiving 50 or 200 mg/kg daily. In
      experiment 2, prostatic weight and prostatic/body weight ratio in the group
      receiving D-004 were similar to those of positive controls. Body weight was not
      affected in any of the groups receiving D-004. CONCLUSIONS: This study of rats
      with T- or DHT-induced PH suggests that D-004 at 200 to 800 mg/kg daily
      administered orally prevents T-induced PH, and that D-004 at 800 mg/kg daily does
      not prevent DHT-induced PH.

PMID- 24672106
TI  - Editorial.

PMID- 24672107
TI  - Effects of flow rate on hemodynamic parameters and agent consumption in low-flow
      desflurane anesthesia: An open-label, prospective study in 90 patients.
AB  - BACKGROUND: In surgical patients, decreasing the fresh gas flow rate in
      anesthesia may minimize costs, reduce environmental pollution, and preserve heat
      and humidity in the respiratory system. OBJECTIVE: The aim of this study was to
      investigate the effects of 3 low-flowdesflurane rates on perioperative
      hemodynamic stability, end-tidal desflurane concentration, emergence and recovery
      characteristics, and agent consumption. METHODS: This open-label, prospective
      study was conducted at the Departmentof Anesthesiology and Reanimation,
      University of Gaziantep, Gaziantep, Turkey. Nonpremedicated adult patients
      scheduled to undergo surgery (ureterolithotomy, cholecystectomy, pyelolithotomy,
      or thyroidectomy) were enrolled. Patients were anesthetized with propofol and
      fentanyl and intubated after neuromuscular blockade with vecuronium. Patients
      were randomly allocated to 1 of 3 groups according to the fresh gas flow rate:
      medium flow (2 L/min), low flow (1 L/min), and minimal flow (0.5 L/min).
      Intraoperative fentanyl volume was recorded. Heart rate, mean arterial pressure,
      and end-tidal desflurane concentration were recorded before (baseline) and after
      anesthesia induction; immediately before incision; and 5, 10, 15, 30, 45, and 60
      minutes after incision. Emergence time and desflurane consumption after
      extubation were recorded. Aldrete scores were recorded at 5, 15, and 30 minutes
      after extubation. RESULTS: Ninety patients (46 women, 44 men; mean [SD] age,
      39.74 [13.73] years; 30 patients per treatment group) participated in the study.
      Means of hemodynamic parameters, intraoperative volume of fentanyl, end-tidal
      desflurane concentration, emergence time, and Aldrete score were statistically
      similar between the 3 groups. Mean (SD) desflurane consumption was significantly
      higher in the medium-flow group compared with the low- and minimal-flow groups
      (110.43 [28.18] g vs 98.40 [23.62] g and 79.80 [17.54] g, respectively; both, P <
      0.01). Mean (SD) desflurane consumption was also significantly higher in the low
      flow group compared with the minimal-flow group (P < 0.01). CONCLUSION: The
      results of the present study in adult surgical patients suggestthat desflurane
      may be used in low-flow anesthesia, even with the minimal fresh gas flow rate.

PMID- 24672108
TI  - Effects of oral crystalline cyanocobalamin 1000 MUg/d in the treatment of
      pernicious anemia: An open-label, prospective study in Ten Patients.
AB  - BACKGROUND: Standard treatment of cobalamin (vitamin B12) deficiency
      involvesregular (1000 MUg/mo) IM cyanocobalamin administration. It has been
      suggested that high-dose (>2000 MUg/d) oral cyanocobalamin may be effective in
      patients with pernicious anemia. OBJECTIVE: The aim of this study was to assess
      the efficacy and tolerability of oral crystalline cyanocobalamin 1000 MUg/d in
      patients with cobalamin deficiency related to established pernicious anemia.
      METHODS: This open-label, prospective study was conducted at StrasbourgUniversity
      Hospital, Strasbourg, France. Patients aged >=18 years with well-documented
      cobalamin deficiency related to pernicious anemia were enrolled. Patients
      received crystalline cyanocobalamin 1000 MUg QD PO (capsule) for at least 3
      months. Serum cobalamin, folate, iron, and homocysteine concentrations were
      measured, and a complete blood count was obtained, before (month 0; baseline) and
      after treatment. RESULTS: Ten patients (7 women, 3 men; mean [SD] age, 72.1
      [15.5] years) entered the study. After 3 months of treatment, serum cobalamin
      concentration increased in all 9 patients in whom it was measured (mean [SD]
      increase, 117.4 [30.8] pg/mL; P < 0.001 vs baseline). Serum cobalamin
      concentrations were normalized (>200 pg/mL) in 6 patients. The serum cobalamin
      concentration was unavailable in 1 patient because of technical problems. Eight
      patients had increased hemoglobin concentrations (mean [SD] increase, 2.5 [2.4]
      g/dL; P < 0.01 vs baseline). All 10 patients had decreased mean erythrocyte
      corpuscular volumes (mean [SD] decrease, 10.4 [6.2] fL; P < 0.003 vs baseline).
      Four patients received concomitant blood transfusions or folate and iron
      supplementation. Three patients experienced clinical improvement in paresthesia,
      reflex abolition, or combined medullary sclerosis (each, 1 patient). CONCLUSION:
      The results of this small study in patients with cobalamin deficiencyrelated to
      pernicious anemia suggest that oral crystalline cyanocobalamin 1000 MUg/d may be
      an effective treatment.

PMID- 24672109
TI  - Preference for and acceptability of twoformulations of a dietary supplement
      containing calcium plus vitamin D3: A randomized, open-label, crossover trial in
      adult patients with calcium and vitamin D deficiencies.
AB  - BACKGROUND: Preference for and acceptability of a drug are crucial for
      complianceand hence optimal treatment of diseases that require long-term
      management (eg, osteoporosis). The preference for and acceptability of a chewable
      tablet containing calcium and vitamin D3 and a dose-comparable effervescent
      powder were assessed in a Phase 4, randomized, open-label, crossover trial in 5
      European countries (Sweden, Finland, Belgium, the Netherlands, and Greece).
      OBJECTIVE: The aim of the present analysis was to compare the preference for and
      acceptability, including tolerability, of these 2 formulations based on the
      Belgian results of the previously mentioned study. METHODS: Patients were
      recruited from 3 osteoporosis units and universityhospitals in Brussels, Liege,
      and Ghent, Belgium. Adult patients at risk for calcium and vitamin D deficiencies
      were enrolled. The study drugs included 2 formulations of a dietary supplement
      containing a combination of calcium plus vitamin D3: chewable tablets (calcium
      carbonate, 1250 mg; vitamin D3, 400 IU) (A) and effervescent powder (calcium
      carbonate, 1250 mg; vitamin D3, 440 IU) (B). Patients were randomly assigned to
      receive 1 of 2 treatment sequences: AB or BA. Both formulations were given PO BID
      for 14 days, with a switch to the alternate formulation occurring on day 15 of
      the study. Preference and acceptability were assessed using 2 questionnaires: one
      assessed 5 variables of acceptability using 11-point scales, and the other
      assessed preference using yes/no questions. Compliance and tolerability were
      recorded throughout the study, with unused dose counts and recording of adverse
      events (AEs), respectively. RESULTS: The study comprised 200 patients, 199 of
      whom received at least 1 dose of study medication and were included in the intent
      to-treat analysis (174 women, 25 men; mean age, 66 years [range, 30-87 years]).
      Preference data were available in 178 patients, 129 of whom (72.5%) preferred the
      chewable tablet compared with 34 (19.1%) who preferred the effervescent powder
      and 15 (8.4%) who had no preference (both, P < 0.001 vs tablet). The preference
      for the tablet was based on consistently and significantly higher mean scores on
      all 5 variables of acceptability (all, P < 0.001). The most common AEs were
      gastrointestinal (tablet, 27/192 patients [14.1%]; powder, 31/190 patients
      [16.3%]). Eighteen patients (9.0%) discontinued the trial due to >=1 AE (12
      receiving the tablet and 6 receiving the powder). CONCLUSIONS: In this study of
      preference for and acceptability of 2 formulations (chewable tablet and
      effervescent powder) of a dietary supplement containing a combination of calcium
      plus vitamin D3 in Belgian adults at risk for calcium and vitamin D deficiencies,
      the chewable tablet was preferred by a significant majority. Based on 5
      variables, the tablet was found to be significantly more acceptable than the
      powder. Tolerability was similar between the 2 formulations.

PMID- 24672111
TI  - Editorial.

PMID- 24672110
TI  - Effects of a single, 24-hour, low-dose intravenous dobutamine infusion on left
      ventricular myocardial performance index in congestive heart failure: A
      prospective, nonrandomized study.
AB  - BACKGROUND: Dobutamine, a predominantly beta-adrenergic sympathomimeticagent, is
      used for improving left ventricular (LV) systolic performance with different
      dosing regimens in patients with congestive heart failure (CHF). Myocardial
      performance index (MPI) is an indicator of LV global function that is correlated
      with LV end-diastolic pressure, and it is increased in CHF. OBJECTIVE: The
      purpose of this study was to examine the effects of a single, 24-hour, low-dose,
      IV dobutamine infusion on LV systolic and diastolic function and on MPI in CHF as
      an indicator of LV global function, as well as the adverse effects (AEs) of the
      infusion. METHODS: This prospective, nonrandomized study was conducted at
      theDepartment of Cardiology, Baskent University Hospital, Ankara, Turkey. Adult
      patients with LV ejection fraction (EF) <35%, sinus rhythm, and symptomatic CHF
      were treated using a standard protocol for at least 4 weeks. At the end of this
      period, patients with symptomatic CHF and EF <35% underwent echocardiography that
      included measuring isovolumic relaxation and contraction times (IRT and ICT,
      respectively) and LV ejection time (ET), and calculating LV MPI using the formula
      MPI = (IRT + ICT)/ET Dobutamine 2.5 MUg/kg . min was then infused intravenously
      for 24 hours. Echocardiography was repeated 24 hours later and values were
      compared with preinfusion data. Patients were observed and monitored for CHF
      symptoms and AEs for 24 hours. RESULTS: Forty-three patients were enrolled in the
      study, and 31 (22 men,9 women; mean [SD] age, 67.55 [11.78] years) continued
      after the 4-week standard-treatment period. Mean (SD) heart rate (74.93 [20.15]
      vs 80.23 [13.74] bpm, respectively), systolic blood pressure (129.00 [19.23] vs
      126.67 [23.79] mm Hg), and diastolic blood pressure (75.80 [11.26] vs 74.96
      [8.30] mm Hg) were statistically similar before and after the infusion. The mean
      (SD) end-diastolic volume was statistically similar to the preinfusion value
      (215.87 [76.74] vs 211.08 [65.51] mL); however, the mean (SD) end-systolic volume
      was significantly reduced (163.80 [63.86] vs 146.74 [53.12] mL; P = 0.01). Mean
      (SD) EF (25.33% [7.77%] vs 30.45% [7.63%]; P = 0.001) and stroke volume (SV)
      (54.92 [22.30] vs 63.59 [23.91] mL; P = 0.04) increased significantly. The mean
      (SD) early:late diastolic flow velocity (E/A ratio) (1.58 [1.36] vs 1.65 [1.27]),
      IRT (107.03 [35.37] vs 100.42 [34.32] ms), ICT (96.61 [34.27] vs 86.35 [44.80]
      ms), ET (240.65 [33.28] vs 243.48 [33.54] ms), and MPI (0.81% [0.28%] vs 0.78%
      [0.31%]) did not change significantly after dobutamine infusion. No AEs were
      observed. CONCLUSIONS: In this study of adult patients with symptomatic CHF, a
      single, 24-hour, low-dose, IV dobutamine infusion (2.5 MUg/kg . min) was
      associated with decreased LV end-systolic volume and increased SV and EF However,
      LV diastolic function parameters, isovolumic time intervals, ET, and MPI were
      statistically similar to preinfusion values. The infusion was well tolerated.

PMID- 24672112
TI  - Increased risk for cardiovascular outcomes and effect of cholesterol-lowering
      pravastatin therapy in patients with diabetes mellitus in the pravastatin anti
      atherosclerosis trial in the elderly (PATE).
AB  - BACKGROUND: The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) was
      the first large-scale, prospective clinical trial to show that cholesterol
      lowering therapy with pravastatin is effective in reducing the risk for
      cardiovascular events (CVEs) in elderly (aged >=60 years) patients with
      hypercholesterolemia. PATE also included a subgroup of patients with diabetes
      mellitus (DM). OBJECTIVE: The aim of this post hoc analysis was to assess the
      effects of lon-gtermpravastatin therapy on cardiovascular outcomes in the
      subgroup of patients with DM compared with a subgroup without it. METHODS: PATE
      was conducted at 50 hospitals, universities, and clinics acrossJapan. Patients
      were randomly allocated to 1 of 2 treatment groups: low-dose pravastatin (5 mg PO
      QD; L group) or standard-lose pravastatin (in Japan, 10 mg PO QD; S group).
      Treatment was given for 3 to 5 years. Serum cholesterol levels were measured and
      the prevalence of CVEs was determined. The primary end point of the study was the
      S:L risk ratio for fatal or nonfatal CVEs. The secondary end point was the effect
      of diabetic patients' glycemic control on CVEs. RESULTS: A total of 665 patients
      (527 women, 138 men; mean [SD] age, 72.8[5.7] years) were followed up for a mean
      of 3.9 years (range, 3-5 years). Among these, 199 patients had DM; 104 patients
      with DM were allocated to the L group and 95 to the S group. Four hundred sixty
      six patients did not have DM (L group, 230 patients; S group, 236 patients).
      Overall, between 3 months and 3 years after the initiation of treatment, patients
      in the L group (mean dose, 4.5 mg/d) experienced reductions from baseline total
      cholesterol level of 11% to 13%. Those in the S group (mean dose, 8.3 mg/d)
      experienced reductions from baseline of 15% to 17%. Decreases in low-density
      lipoprotein cholesterol (LDL-C) levels were 17% to 20% and 23% to 26% in the L
      and S groups, respectively. Statistically similar reductions were noted between
      patients with DM and those without it in response to either dose. The DM subgroup
      experienced 32 CVEs (L group, 17; S group, 15) compared with 39 CVEs (L group,
      25; S group, 14) in the subgroup without DM. The S:L CVE risk ratio (primary end
      point) was 0.94 (95% Cl, 0.46-1.92) in patients with DM and 0.54 (95% Cl, 0.28
      1.05) in those without DM; the differences between the treatment groups were not
      statistically significant. The risk for CVEs in patients with DM whose
      glycosylated hemoglobin concentrations were <8.0% and >=8.0% were, respectively,
      1.87-fold (95% Cl, 1.09-3.20; P = 0.02) and 3.79-fold (95% Cl, 1.92-7.48; P <
      0.01) higher than that in patients without DM. CONCLUSIONS: In this post hoc
      analysis of the effects of long-term cholesterol-loweringtherapy (low- and
      standard-dose pravastatin) on cardiovascular outcomes in elderly patients with
      DM, dose had no effect on the risk for CVEs in these patients as it did in those
      without DM. Poorer glycemic control in patients with DM was related to a higher
      risk for CVEs. The lack of pravastatin efficacy found in the subgroup with DM may
      have been attributable to the small differences in LDL-C levels found between the
      2 treatment groups and/or the small sample size of the study.

PMID- 24672114
TI  - Bioavailability study of fixed-dose tablet versus capsule formulation of
      amlodipine plus benazepril: A randomized, single-dose, two-sequence, two-period,
      open-label, crossover study in healthy volunteers.
AB  - BACKGROUND: In the treatment of hypertension, combination therapy is important10
      because antihypertensive monotherapy is effective in only 40% of patients
      worldwide. Amlodipine is a dihydropyridine calcium channel blocker with a slow
      onset and long duration of action. Benazepril hydrochloride is a prodrug
      hydrolyzed by esterase to the active metabolite benazeprilat, an angiotensin
      converting enzyme inhibitor. In 1995, the US Food and Drug Administration
      approved the use of a capsule formulation of combination amlodipine-benazepril
      for hypertension. OBJECTIVE: The aim of this study was to compare the
      bioavailability and tolerability10 of the capsule formulation with those of a
      tablet formulation of combination amlodipine-benazepril in healthy volunteers.
      METHODS: This single-dose, 2-sequence, 2-period, open-label, crossover10 study
      recruited healthy, adult, male volunteers with normotension. Subjects were
      randomly assigned to 1 of 2 treatment sequences: a single-dose tablet containing
      amlodipine 5 mg plus benazepril 10 mg, followed by a single-dose capsule
      containing the same dose of each drug (AB), or vice versa (BA). The treatment
      period for each drug consisted of dosing and pharmacokinetic analysis on day 1,
      followed by pharmacokinetic analysis on days 2 to 7. Treatment periods were
      separated by a 4-week washout period. For pharmacokinetic analysis, serial blood
      samples were obtained before dosing and at 20, 40, 60, 80, and 100 minutes and 2,
      3, 4, 5, 6, 7, 8, 10, 12, 24, 36, 60, 84, 108, 132, and 156 hours after dosing.
      Tolerability was assessed using subject interview and spontaneous reporting.
      RESULTS: Twelve healthy, male, Taiwanese subjects (mean [SD] age, 23.510 [1.7]
      years) participated in the study. No statistically significant differences
      inbioavailability were found between the 2 formulations based on the
      pharmacokinetic measurements of amlodipine and benazeprilat. The rate and extent
      of absorption of the tablets were found to be comparable to those of the capsules
      (90% CI, between 80% and 125%). The mean (SD) relative bioavailabilities, as
      represented by AUC0-infinity, of amlodipine and benazeprilat for tablets versus
      capsules were 1.060 (0.170) versus 0.949 (0.197), respectively. The mean plasma
      concentration-time profiles of amlodipine and benazeprilat were graphically
      similar. No adverse effects were observed with either formulation. CONCLUSIONS:
      The results of this bioavailability comparison study in this 10 population of
      healthy, male, Taiwanese volunteers suggest that the tablet and capsule
      formulations of combination amlodipine-benazepril are bioequivalent. Both
      formulations were well tolerated.

PMID- 24672115
TI  - Status of lipid-lowering therapy prescribedbased on recommendations in the 2002
      report of the Japan Atherosclerosis Society Guideline for Diagnosis and Treatment
      of Hyperlipidemia in Japanese Adults: A study of the Japan Lipid Assessment
      Program (J-LAP).
AB  - BACKGROUND: In its 1997 Guideline for Diagnosis and Treatment of Hyperlipidemia
      in Japanese Adults and subsequent revisions, the Japan10 Atherosclerosis Society
      (JAS) recommends serum lipid management goals (SLMGs) based on a coronary heart
      disease (CHD) risk classification. A literature search revealed that the status
      of lipid-lowering therapy based on the current JAS recommendations in Japan has
      not been assessed. OBJECTIVE: The aim of this study was to evaluate the efficacy
      of current lipid-lowering 10 regimens, and to provide the best possible
      therapeutic strategies for patients with hyperlipidemia by identifying risk
      factors for the development of CHD, based on the current JAS recommendations.
      METHODS: This multicenter, retrospective study was conducted using data 10 from
      patients under the care of physicians at 12,500 randomly selected institutions
      across Japan. Physicians received a survey concerning lipid-lowering therapy, on
      which each physician provided data from 10 consecutive adult patients with
      hyperlipidemia who had been prescribed lipid-lowering therapy for at least 3
      months before the survey was administered, and who were undergoing routine follow
      up on an outpatient basis. Physicians provided patients' demographic and clinical
      data, including JAS-defined CHD risk classification coronary risk factors and pre
      and posttreatment (after >=3 months) serum lipid levels, and the types and
      dosages of drugs in patients' current and prior treatment regimens. These data
      were used to assess the efficacy of lipid-lowering regimens and rates of patients
      achieving the SLMGs recommended by the JAS. RESULTS: A total of 2540 physicians
      participated in the survey, and data from 10 24,893 Japanese patients (mean [SD]
      age, 65.8 [10.5] years) with hyperlipidemia were included in the study. Patients
      with familial hyperlipidemia (845/24,893 [3.4%]) were excluded from most of the
      analyses, leaving 24,048 patients with primary hyperlipidemia. The most prevalent
      coronary risk factors included age (21,902 [91.1%]), hypertension (14,275
      [59.4%]), diabetes mellitus type 2 and/or impaired glucose tolerance (6346
      [26.4%]), and smoking (3841 [16.0%]). A total of 20,948 patients (87.1%) had a
      CHD risk classification of B (ie, >=1 coronary risk factor but no history of
      CHD). At the time of the survey, the lipid-lowering regimens of 22,080 patients
      (91.8%) included a statin. The rates of achievement of SLMGs were as follows:
      total cholesterol (TC), 12,659/23,840 patients (53.1%); low-density lipoprotein
      cholesterol (LDL-C), 14,025/22,121 (63.4%); high-density lipoprotein cholesterol,
      19,702/21,279 (92.6%); and triglycerides (TG), 14,892/ 23,569 (63.2%). TC and LDL
      C goals were achieved by most patients (>=61.1%) in risk categories A, B1, and B2
      (ie, 0-2 coronary risk factors; low to moderate risk) but by a low percentage of
      patients (<=45.4%) in risk categories B3, B4, and C (ie, >=3 coronary risk
      factors or history of CHD; high risk). In the high-risk group (n = 10,515), the
      TC goal was achieved by 4059 patients (38.6%). The TC and LDL-C goals were
      achieved by significantly higher percentages of patients prescribed atorvastatin
      (5133/7928 [64.7%] and 5487/7426 [73.9%], respectively) compared with the rates
      of patients prescribed any other statin at the recommended starting doses (all, P
      < 0.05). CONCLUSIONS: The results of this study of Japanese patients undergoing
      lipid-lowering 10 therapy for the prevention of CHD, prescribed based on the
      recommendations in the JAS guideline, suggest insufficient reduction of TC, LDL
      C, and TG in patients at high risk for CHD and the need for more aggressive lipid
      lowering therapy in such patients.

PMID- 24672116
TI  - Antidepressant-related adverse effects impacting treatment compliance: Results of
      a patient survey.
AB  - BACKGROUND: Despite the high prevalence of depression in the United States, 10
      few studies have identified which adverse effects (AEs) patients are willing or
      unwilling to tolerate when receiving antidepressants. OBJECTIVE: The aim of this
      study was to identify reasons for discontinuation10 and noncompliance with
      antidepressant medications, the impact of AEs on compliance and quality of life
      (assessed using impact of AEs on activities of daily living), and patients'
      suggestions for improving their medication, using a patient survey. METHODS:
      Patients aged 18 to 65 years with mild to severe depression were 10 randomly
      selected by their physicians to be sent an invitation to complete the 42-question
      survey. Three hundred physicians nationwide assessed the severity of depression
      and symptoms of anxiety in each respondent, using their judgment. Patients were
      asked specific questions to assess reasons for discontinuation/noncompliance.
      Patients were also asked to rate AEs based on how difficult they were to "live
      with," and what 2 aspects of their antidepressant medication they would change if
      they could. RESULTS: In a separate, concurrent study, physicians classified 175
      (50%) abdResults:0 mildly to moderately depressed and 84 (24%) as severely
      depressed. Ninety-one respondents (26%) were classified as having symptoms of
      anxiety. Two hundred seven patients (60%) indicated they had discontinued
      treatment with an antidepressant agent at some point in their lives, the most
      common reason for which was lack of efficacy (92 patients [44%]). Of the 344
      patients currently being treated with an antidepressant, 75 (22%) reported
      noncompliance. The most common reasons for noncompliance were "have trouble
      remembering to take it" (19/44 patients [43%]), "gained a lot of weight" (11/41
      [27%]), "unable to have an orgasm" (8/40 [20%]), and "lost interest in sex" (8/41
      [20%]). The 4 AEs patients expressed as "extremely difficult to live with" were
      "weight gain" (104 patients [31%]), "unable to have erection" (83 [25%]),
      "difficulty reaching orgasm" (80 [24%]), and "tired during the day/no energy" (69
      patients [21%]). The 3 most frequently cited improvements patients (n = 327)
      would make to their medications were better efficacy (176 patients [54%]) and
      eliminating AEs related to sexual desire and weight gain (112 [34%] and 105 [32%]
      patients, respectively). CONCLUSIONS: The findings of this survey of patients
      with mild to severe10 depression suggest that compliance, and hence efficacy, can
      be promoted by (1) understanding what patients expect and desire from the
      antidepressants they are prescribed and (2) prescribing antidepressants
      associated with low rates of weight gain, sexual dysfunction, or tiredness.

PMID- 24672117
TI  - Comparison of the effects of lornoxicam versus diclofenac in pain management
      after cardiac surgery: A single-blind, randomized, active-controlled study.
AB  - BACKGROUND: Inadequate pain management after cardiac surgery may result 10 in
      increased morbidity and length of hospital stay. Although opioids are the
      mainstay of postoperative analgesia, nonsteroidal anti-inflammatory drugs
      (NSAIDs) may be used instead to avoid the adverse effects (AEs) associated with
      opioids. Lornoxicam is a newly developed NSAID, the use of which is increasing.
      However, lornoxicam has not been studied for use in pain management after cardiac
      surgery. OBJECTIVE: The objective of this study was to compare the efficacy and
      tolerability 10 of lornoxicam and diclofenac sodium, an NSAID well established
      for use in pain management after major surgery, in pain management after coronary
      artery bypass grafting (CABG). METHODS: This single-blind, randomized, active
      controlled study was conducted 10 at the Gaziantep University Hospital,
      Gaziantep, Turkey. Adult patients scheduled to undergo valve or CABG surgery for
      the first time were included. Patients were premedicated with diazepam 10 mg PO
      at 10 PM on the evening before surgery. General anesthesia was induced using
      fentanyl, midazolam, and propofol, and maintained using fentanyl and isoflurane
      in pure oxygen. After extubation and when they stated that they felt pain,
      patients were randomly assigned to 1 of 2 treatment groups: lornoxicam 8 mg IM
      q8h or diclofenac 75 mg IM q12h, for 48 hours. Meperidine 1 mg/kg IM was given
      for additional analgesia when needed (rescue medication). Pain relief was
      assessed using an I1-point visual analog scale (0 = no pain to 10 = worst pain
      imaginable) immediately before the first injection (baseline), and at 15 and 30
      minutes and 1, 2, 3, 4, 6, 12, 18, 24, and 48 hours after the first injection.
      Sedation was assessed using a 5-point scale (0 = awake and alert to 4 = deep
      sedation) at the same time points. Tolerability was assessed by monitoring of AEs
      using patient interview and laboratory analyses. RESULTS: Forty patients were
      enrolled in the study (30 men, 10 women; 10 mean [SD] age, 54.4 [11.1 ] years; 20
      patients per treatment group). The demographic and clinical characteristics and
      mean baseline pain relief scores were statistically similar between the 2
      treatment groups. The mean pain relief scores at 15 and 30 minutes were
      statistically similar to baseline values in the 2 treatment groups. However, the
      mean pain relief scores at >=1 hour after the first injection were significantly
      lower compared with baseline values (both groups, P < 0.05 at time points >=1
      hour). No significant between-group differences in mean pain relief scores were
      found at any time point. The overall mean pain relief scores were statistically
      similar between the 2 treatment groups. The mean sedation scores were
      significantly higher at 30 minutes, 1 hour, and 2 hours after the first injection
      in the diclofenac group compared with the lornoxicam group (all, P < 0.05). No
      AEs were observed. The need for rescue medication was statistically similar
      between the 2 treatment groups (lornoxicam, 2 patients; diclofenac, 3 patients).
      CONCLUSIONS: In this study of adult patients who underwent CABG, the efficacy 10
      of lornoxicam and diclofenac were similar in postoperative pain management. Both
      study drugs were well tolerated.

PMID- 24672118
TI  - Treatment-limiting toxicities associated withnucleoside analogue reverse
      transcriptase inhibitor therapy: A prospective, observational study.
AB  - BACKGROUND: The Recover Study is an ongoing, prospective study designed 10 to
      assess toxicity associated with the use of nucleoside analogue reverse
      transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine,
      abacavir) in HIV-1-infected patients receiving highly active antiretroviral
      therapy (HAART) in routine clinical practice. This project is being conducted at
      120 HIV units at teaching hospitals across Spain. OBJECTIVE: The aim of this
      study was to identify the most common treatment-limiting 10 moderate to severe
      clinical and laboratory adverse effects (AEs), and the individual NRTIs involved
      in the development of these effects, in HIV-1-infected patients receiving HAART
      who discontinued use of an NRTI in the Recover Study. METHODS: Patients eligible
      for participation in the Recover Study are aged10 >=18 years; have virologically
      documented HIV-1 infection; have sustained viral suppression (viral load <200
      cells/mL or stable, heavily experienced [ie, have received >=3 antiretroviral
      regimens] patients with viral load <5000 cells/mL) for >=6 months; are receiving
      HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE
      that, in the opinion of a study investigator and under the conditions of routine
      clinical practice, justified discontinuation of treatment with the offending drug
      (principal AE/offending NRTI). The present study included patients recruited for
      the Recover Study between September 2002 and May 2003. RESULTS: A total of 1391
      patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18-67
      years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean
      duration of treatment with the offending NRTI was 74 months (range, 6-156
      months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more)
      therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside
      analogues, and 552 patients (39.7%), protease inhibitors, as components of their
      HAART regimens. The NRTIs with the highest discontinuation rates were stavudine
      (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI
      related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy
      (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550
      cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170
      [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine
      (70/77 cases [90.9%]). CONCLUSIONS: The results of this study in patients with
      HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long
      term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral
      neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy,
      lipodystrophy) being the most common AEs leading to discontinuation. Minimizing
      these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir)
      would contribute to adherence and hence efficacy of long-term HAART.

PMID- 24672119
TI  - Ketolides in the treatment of community-acquired respiratory tract infections: A
      review.
AB  - BACKGROUND: The increasing prevalence of resistance to established antibiotics
      among key respiratory bacterial pathogens highlights a need for new antibacterial
      agents for the treatment of community-acquired respiratory tract infections
      (RTIs). Ketolides are a new class of antibiotics specifically developed for the
      treatment of RTIs. OBJECTIVE: The aim of this review was to present the current
      status of treatment of RTIs with ketolides, focusing on telithromycin-the first
      ketolide to be approved by the US Food and Drug Administration for clinical use.
      METHODS: TO GATHER EVIDENCE ON THE CURRENT STATUS OF KETOLIDES, A LITERATURE
      SEARCH WAS CONDUCTED USING MEDLINE (YEARS: 1990-2005; key terms: ketolides,
      telithromycin, and HMR3647). RESULTS: Telithromycin shows strong in vitro
      activity against the major respiratorypathogens, including strains resistant to
      other antibiotics, as well as the atypical respiratory pathogens. The
      pharmacokinetic properties of telithromycin are compatible with once-daily
      dosing. Clinical trials have demonstrated that telithromycin 800 mg QD for 5 to
      10 days is effective in the treatment of acute bacterial sinusitis, acute
      bacterial exacerbations of chronic bronchitis, and mild to moderate community
      acquired pneumonia. Overall, telithromycin is well tolerated by patients. Drug
      drug interactions are similar to those reported for macrolides. CONCLUSION:
      Evidence to date indicates that telithromycin is an effective andwell-tolerated
      empiric treatment for community-acquired RTIs.

PMID- 24672121
TI  - Effectiveness and tolerability of once-daily nimesulide versus ibuprofen in pain
      management after surgical extraction of an impacted third molar: A 24-hour,
      double-blind, randomized, double-dummy, parallel-group study.
AB  - BACKGROUND: Nimesulide is a nonsteroidal, anti-inflammatory drug that hasbeen
      used for a wide range of acute and chronic pain. A once-daily formulation of
      nimesulide is now commercially available, but its effectiveness in pain
      management after dental surgery has not been assessed. OBJECTIVE: The aim of this
      study was to assess the analgesic effectiveness and tolerability of oral
      treatment with once-daily nimesulide versus ibuprofen q6h over 24 hours in
      patients with postoperative pain associated with surgical extraction of an
      impacted third molar. METHODS: This 24-hour, double-blind, randomized, double
      dummy, parallel-groupstudy was conducted at a private practice in Caracas,
      Venezuela. Patients aged between 12 and 60 years with moderate to severe pain
      after extraction of an impacted third molar were enrolled. Patients were
      randomized to receive a single dose of nimesulide (300-mg tablet) or ibuprofen
      (400-mg tablets) q6h for 24 hours. For double-dummy design, patients in the
      nimesulide group also received ibuprofen placebo tablets, to be taken q6h for 24
      hours, and patients in the ibuprofen group received a nimesulide placebo tablet.
      The primary end points were pain intensity (PI) and pain relief scores over 24
      hours. Secondary end points included total pain relief, PI difference (PID), sum
      of PID (SPID), time to first measurable change in PI (ie, PID >= 10 mm), and use
      of rescue medication (acetaminophen). Patients also rated the treatment's
      effectiveness as very poor to very good on questioning by the study investigator.
      Spontaneously reported adverse effects (AEs) were recorded. RESULTS: Eighty-six
      patients were enrolled (56 females, 30 males), with 43 patientsper treatment
      group (mean age: nimesulide group, 25.2 years; ibuprofen group, 24.2 years). The
      baseline characteristics were statistically similar between the 2 groups.
      Compared with baseline, mean PI scores were significantly lower in both treatment
      groups at all time points throughout the study (P < 0.001). Mean PI scores were
      significantly lower in the nimesulide group compared with the ibuprofen group at
      15 and 45 minutes and 1 hour after study drug administration (P <= 0.049). Time
      to first measurable change in PI was within the first 15 minutes in 22 patients
      (52%) in the nimesulide group and in 14 patients (33%) in the ibuprofen group (P
      = 0.03). Analgesia lasted 24 hours with nimesulide and ibuprofen (PI scores at 24
      hours, 9.4 and 3.6, respectively). The mean PR score was significantly lower in
      the nimesulide group compared with the ibuprofen group at 1 hour after study drug
      administration (P = 0.049). Compared with baseline, PID and SPID were
      significantly higher in both treatment groups throughout the study (P < 0.001).
      Significantly more patients in the nimesulide group than in the ibuprofen group
      reported that treatment provided effective pain relief (82% vs 73%; P = 0.013).
      No AEs were reported in either treatment group throughout the study. Use of
      rescue medication was statistically similar between the nimesulide and ibuprofen
      groups (38% and 31%, respectively). CONCLUSIONS: In this study of patients with
      moderate to severe pain afterextraction of impacted third molars, nimesulide and
      ibuprofen provided effective 24-hour relief. However, the results suggest that
      the analgesic effect of nimesulide had a faster onset (<15 minutes) and was
      stronger (based on patient opinion) than that of ibuprofen. Both study drugs were
      well tolerated.

PMID- 24672120
TI  - Relative efficacy and interchangeability ofvarious clobetasol propionate vehicles
      in the management of steroid-responsive dermatoses.
AB  - BACKGROUND: Topical corticosteroids have long been the cornerstone in
      thetreatment of steroid-responsive dermatoses. Despite the effectiveness of these
      formulations, there is a misperception that drugs delivered via ointments are
      more potent than those delivered via other vehicles. Potency, however, is a
      complex function of the physical and chemical properties of both the active
      ingredient and its vehicle. Studies have determined that newer vehicles (eg,
      lotions), particularly those in the super-high-potency class, not only heighten
      the ability of the active ingredient to penetrate skin but also are preferred by
      patients over ointments and creams. OBJECTIVE: This review of the literature
      investigates the effectiveness andtolerability of a high-potency corticosteroid
      lotion compared with cream or emollient cream formulations in treating moderate
      to severe plaque-type psoriasis and atopic dermatitis. METHODS: A literature
      search was conducted of US and international published clinical trials (1975 to
      November 2004) comparing all potencies of topical corticosteroid cream and lotion
      formulations using MEDLINE and the Web sites of individual dermatologic journals.
      No specific study designs were excluded from this search. Search terms included
      corticosteroid-responsive dermatoses, creams versus lotions, topical
      corticosteroid clinical trials, plaque-type psoriasis, atopic dermatitis,
      clobetasol propionate, drug bioavailability, Class I topical agents, and
      vasoconstriction. The primary diagnoses were moderate to severe plaque-type
      psoriasis and atopic dermatitis. Two unpublished clinical investigations
      comparing clobetasol propionate lotion 0.05% with clobetasol propionate cream
      0.05% and emollient cream 0.05% in a total of 421 patients were also included.
      RESULTS: In the 20 published and 2 unpublished trials identified and reviewed,
      the response rates were comparable between the lotion and cream formulations. In
      addition, in a psoriasis study, clobetasol lotion received significantly better
      cosmetic-acceptability ratings compared with clobetasol cream (P < 0.05).
      CONCLUSION: In the studies reviewed, the effectiveness and tolerability of
      clobetasollotion were comparable to those of clobetasol cream and emollient cream
      in studies in adults with moderate to severe psoriasis or atopic dermatitis.

PMID- 24672122
TI  - Effects of angiotensin II-receptor blockers on soluble cell adhesion molecule
      levels in uncomplicated systemic hypertension: An observational, controlled pilot
      study in Taiwanese adults.
AB  - BACKGROUND: Controversy exists as to whether individuals with hypertension
      without risk factors for atherosclerosis (eg, diabetes mellitus, dyslipidemia.
      OBJECTIVE: The aim of this study was to determine whether (1) levels of
      solubleCAMs (sCAMs) (soluble E-selectin [sE-selectin], soluble intercellular
      adhesion molecule-1 [sICAM-1 ], soluble vascular cell adhesion molecule-1 [sVCAM
      1 ], and von Willebrand factor [vWF]) are elevated in Taiwanese adults with
      uncomplicated essential hypertension without other risk factors; (2) CAM levels
      increase with severity (stage) of hypertension; and (3) monotherapy with the
      angiotensin II-receptor blocker (ARB) irbesartan modulates CAM expression in a
      subgroup of these patients. METHODS: This observational, controlled pilot study
      was conducted at the Hypertension Clinic, Department of Internal Medicine,
      Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Adult patients with
      uncomplicated essential hypertension without other risk factors (eg, diabetes
      mellitus, dyslipidemia, obesity) and normotensive controls were eligible. Blood
      pressure (BP) was determined using 24-hour ambulatory BP monitoring (ABPM) in all
      participants, and the staging of hypertension was classified based on criteria in
      The Seventh Report of the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure (normotensive, prehypertension,
      stage I hypertension, and stage II hypertension). The SCAM levels and 24-hour
      ABPM were measured before and after 8 weeks of open-label irbesartan monotherapy
      in a subgroup of the patients with hypertension. Patients who had difficulty
      achieving the target BP values on irbesartan monotherapy were treated with
      combination therapy (2 or 3 antihypertensive agents); levels of sCAMs were not
      measured in these patients. Plasma levels of sE-selectin, the sCAMs, and vWF were
      measured using enzyme-linked immunosorbent assay. RESULTS: The study comprised 61
      patients with uncomplicated essentialhypertension (33 men and 28 women; mean [SD]
      age, 51 [12] years) and 17 normotensive controls (11 men, 6 women; mean [SD] age,
      52 [ 11 ] years). The mean (SD) dose of irbesartan was 243 (63) mg. Hypertensive
      patients had significantly higher circulating levels of sICAM-1 compared with
      normotensive controls (P = 0.009). No significant differences in levels of sVCAM
      1, sE-selectin, or vWF were found between hypertensive patients and controls. The
      mean sICAM-1 level was significantly higher in the prehypertensive patients
      compared with normotensive controls (P = 0.03). The mean sE-selectin level was
      significantly higher in the patients with stage I hypertension compared with the
      prehypertensive group (P = 0.01). The 18 patients given 8 weeks of irbesartan
      monotherapy showed a significant decrease from baseline in systolic and diastolic
      BP (both, P = 0.001) and sE-selectin (P= 0.006), but not in sVCAM-1 or sICAM.
      Forty-three patients did not reach target BP on irbesartan monotherapy and thus
      were treated with combination therapy. CONCLUSIONS: Based on the results of this
      observational, controlled pilotstudy in Taiwanese patients, we suggest that ARB
      therapy, in addition to reducing BP, has the potential to suppress CAM expression
      and to improve endothelial dysfunction in hypertension.

PMID- 24672123
TI  - Unit dosing of darbepoetin alfa for thetreatment of anemia in patients with end
      stage renal disease being switched from recombinant human erythropoietin: Results
      of a phase IIIb, 27-week, multicenter, open-label study in Greek patients.
AB  - BACKGROUND: Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a
      ~3-fold longer t1/2 and greater biological activity compared with recombinant
      human erythropoietin (rHuEPO). OBJECTIVE: The objective of this study was to
      evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa
      treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10
      to 13 g/dL in patients undergoing dialysis; the patients were switched from
      rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase
      in dose. METHODS: In this Phase IIlb, open-label, multicenter study, patients
      withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO
      BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving
      rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin
      alfa was by the same route as previous rHuEPO administration (IV or SC). Patients
      received darbepoetin alfa for 24 weeks, including a 20-week drug titration period
      followed by a 4-week, stable-dose evaluation period. The mode, dose, and
      frequency of administration of darbepoetin alfa were compared with those of
      baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and
      laboratory tests (hematology, vital sign measurement, iron status, and
      biochemistry). RESULTS: The study comprised 173 patients who were divided into 2
      groups by route of administration (IV group, n = 146; SC group, n = 27). Mean
      (SE) adjusted increases in Hb concentration from baseline to the evaluation
      period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38
      (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS,
      respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted
      increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the
      IV and SC routes, respectively (both, P = NS). No significant differences in
      IV/SC dose ratio were observed between the 2 routes of administration. In
      addition, no increases in darbepoetin alfa dose were observed. The most commonly
      reported adverse events were hypertension (8 patients [5%]) and vascular access
      thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6
      (3%). CONCLUSIONS: Darbepoetin alfa effectively maintained Hb concentrations
      within the target range without an increase in dose, even at a reduced dosing
      frequency. Overall, darbepoetin alfa was well tolerated.

PMID- 24672124
TI  - Levetiracetam in the preventive treatmentof transformed migraine: A prospective,
      open-label, pilot study.
AB  - BACKGROUND: Most preventive agents used for transformed migraine (TM)have not
      been studied specifically for the treatment of this syndrome. Open-label trials
      have demonstrated the effectiveness of levetiracetam in the treatment of
      refractory headaches. OBJECTIVE: The aim of this study was to assess the
      effectiveness and tolerabilityof levetiracetam in the preventive treatment of
      refractory TM. METHODS: This prospective, open-label, pilot study was conducted
      at TheNew England Center for Headache, Stamford, Connecticut. We included
      patients aged >= 18 years with refractory TM according to the criteria proposed
      by Silberstein et al. All participants had failed on at least 1 but not more than
      3 preventive drugs. Other preventive drugs were allowed if they had been received
      at a stable dose for > 30 days. The dosage of the levetiracetam tablets ranged
      from 1000 to 3000 mg/d in 2 divided doses. The treatment phase lasted 3 months.
      The primary end point was headache frequency (expressed as the number of headache
      days per month), and the secondary end point was the frequency of moderate or
      severe headache (d/mo). Other end points were headache score, Migraine Disability
      Assessment (MIDAS) Questionnaire score, and Headache Impact Test (HIT-6) score.
      Statistical analyses were performed in the intent-to-treat (ITT) population
      (patients who received at least 1 dose of study medication) using data subjected
      to the last-observation-carried-forward algorithm. We also conducted per-protocol
      (PP) analyses in patients who completed the study. RESULTS: The ITT population
      consisted of 36 patients (26 women, 10 men;mean [SD] age, 46.5 [17.4] years). The
      mean headache frequency at baseline was 24.9 d/mo, and a significant reduction in
      headache frequency was obtained at l, 2, and 3 months of treatment (19.4, 18.4,
      and 16.2 d/mo, respectively; all, P < 0.001 Reproduction in whole or part is not
      permitted. vs baseline). At baseline, the mean number of moderate or severe
      headache days was 16.8 d/mo compared with 13.2, 11.9, and 9.7 d/mo at 1, 2, and 3
      months, respectively (P=NS, <0.01, and <0.01, respectively). The mean MIDAS score
      was significantly reduced at 3 months compared with baseline (40.8 vs 62.8 d/mo;
      P = 0.01). The mean HIT-6 score was 59.4 at 3 months versus 63.4 at baseline (P <
      0.01). In the PP population, the mean (SD) headache frequency was reduced from
      26.1 (4.1) d/mo at baseline to 14.3 (4.8) d/mo at the end of the study (P <
      0.001). The mean (SD) headache score was reduced from 51.3 (17.1) at baseline to
      34.0 (22.0) at 3 months (P < 0.016). CONCLUSION: The results of this study in
      patients with TM support the role of levetiracetam in the preventive treatment of
      refractory TM.

PMID- 24672125
TI  - Efficacy of moxifloxacin monotherapy versusgatifloxacin monotherapy, piperacillin
      tazobactam combination therapy, and lindamycin plus gentamicin combination
      therapy: An experimental study in a rat model of intra-abdominal sepsis induced
      by fluoroquinolone-resistant Bacteroides fragilis.
AB  - BACKGROUND: In intra-abdominal infections, the activity of antimicrobial agents
      against Bacteroides fragilis and phenotypically related organisms, and the
      increasing resistance of these organisms, are of particular importance and
      concern to surgeons. In vitro data suggest that moxifloxacin is more active than
      other quinolones against obligately anaerobic organisms, including Bacteroides
      spp. OBJECTIVE: The aim of this study was to compare the efficacy of moxifloxacin
      monotherapy versus gatifloxacin monotherapy and 2 combination therapies
      (piperacillin-tazobactam and clindamycin plus gentamicin) in a rat model of intra
      abdominal sepsis. The end point was marked by the incidence of mortality and
      intra-abdominal abscesses at necropsy 7 days after bacterial challenge. METHODS:
      Three different strains of B fragilis with different degrees of resistanceto
      moxifloxacin (minimum inhibitory concentrations [MICs]: 4, 8, and 16 pg/mL) were
      added to the challenge inoculum in 3 separate experiments. Groups of 20 animals
      were used in each experiment. Group 1 served as saline-treated controls; group 2
      received moxifloxacin 15 mg QD; group 3 received gatifloxacin 25 mg QD; group 4
      received piperacillin-tazobactam 93 mg (-83 mg of piperacillin) QD; and group 5
      received a combination of clindamycin 15 mg TID plus gentamicin 2 mg TID. All
      treatments were given intramuscularly. For all antimicrobials, dose was based on
      peak and trough serum drug concentrations determined by prior testing, with
      animal doses adjusted based on the ratio of body surface area to body weight, and
      comparing these doses and levels with studies in humans. RESULTS: In all 3
      experiments, the mortality rate with moxifloxacin was significantlylower or
      statistically similar compared with antibiotic active comparators (P <= 0.024).
      In addition, there were no significant differences in the incidence of abscess
      with moxifloxacin versus its comparators or between the 3 moxifloxacin groups
      across experiments. The best results for moxifloxacin were found in the
      experiment in which the B fragilis strain with MIC 16 MUg/mL was added to the
      inoculum. CONCLUSION: The results of this study in an animal model of intra
      abdominalsepsis induced by fluoroquinolone-resistant B fragilis suggest that
      moxifloxacin monotherapy performs as well as combination regimens such as
      piperacillin-tazobactam and clindamycin plus gentamicin, and is as effective as
      other fluoroquinolones with antianaerobic activity, such as gatifloxacin.

PMID- 24672126
TI  - Effects of lamotrigine monotherapy in patients with newly diagnosed juvenile
      myoclonic epilepsy: An open-label study.
AB  - BACKGROUND: It is important that drug therapy for juvenile myoclonic
      epilepsy(JME), a lifelong disorder requiring long-term therapy, is effective and
      well tolerated with long-term use. Lamotrigine as monotherapy or adjunctive
      therapy has been demonstrated to be effective in reducing the frequency of
      partial and generalized seizures in short- and long-term studies in children,
      adolescents, adults, and elderly patients with epilepsy, including those with
      JME. With its tolerability profile and spectrum of efficacy, lamotrigine might be
      an appropriate option for newly diagnosed patients with JME, a possibility that
      has not been empirically assessed. OBJECTIVE: The aim of this study was to assess
      the efficacy and tolerability of lamotrigine monotherapy in patients with newly
      diagnosed JME. METHODS: This open-label study was conducted at 18 clinical sites
      across the United States. Patients aged >=12 years with newly diagnosed JME and
      who had experienced at least 1 generalized motor seizure since diagnosis but were
      antiepileptic treatment-naive or had received inappropriate treatment due to
      misdiagnosis were enrolled. During the first 8 weeks of the study, lamotrigine
      (25-mg or 100-mg tablets) was introduced (to a maximum dosage of 100-500 mg/d,
      based on instructions in the package insert and clinical response). This dose
      escalation was followed by a 24-week treatment phase during which lamotrigine
      dose could be adjusted as needed to achieve optimal clinical benefit. Efficacy
      end points included the rates of patients with a decrease from baseline of at
      least 50% in the frequency of myoclonic, tonic-clonic, and absence seizures; and
      the rate of patients with mild, moderate, or marked improvement from baseline in
      global clinical status as perceived by the investigators. Adverse events were
      recorded in patient diaries, and diary information was reviewed by study
      personnel at clinic visits. Results were analyzed using descriptive statistics.
      RESULTS: Twenty-nine patients (17 females, 12 males; mean [SD] age, 24.0 [11.3]
      years [range, 12-50 years]) were included in the efficacy analysis. During the
      lamotrigine monotherapy treatment period, 58% of patients experienced a reduction
      from baseline of at least 50% in days with myoclonic seizures, and 56% and 38% of
      patients experienced a reduction of at least 50% in the frequency of generalized
      tonic-clonic seizures and absence seizures, respectively. At week 24 of the
      monotherapy phase, investigators perceived that 72% of patients had shown mild,
      moderate, or marked improvement in global clinical status relative to the start
      of the study. CONCLUSIONS: In this study, lamotrigine monotherapy given to
      patients with newly diagnosed JME was associated with a reduction in the
      frequency of seizures and improvement in global clinical status as rated by the
      investigators. Lamotrigine was generally well tolerated.

PMID- 24672127
TI  - Pharmacokinetic properties of pravastatin in Mexicans: An open-label study in
      healthy adult volunteers.
AB  - BACKGROUND: The pharmacokinetic properties of pravastatin, particularlyAUC and
      Cmax, are variable by population. A description of the pharmacokinetic properties
      of pravastatin in Mexican mestizos was not found in a search of MEDLINE/PubMed
      (key terms: pravastatin, Mexican, and pharmacokinetics; years: 1966-2005).
      Because Mexicans and Japanese have common ancestors (Mongoloid group), they also
      have a common gene pool. This gene pool was modified by genetic "bottlenecks"
      that occurred when these populations migrated to the Americas and when the
      Mexican population mixed with the Spanish population during the 16th and 17th
      centuries. Previous studies in Japanese subjects showed 5 main mutations on the
      hepatic drug transporter OATP-C, resulting in higher Cmax and AUC values compared
      with whites. In the Japanese population, the rates of expression of the (*) 1b
      and (*) 15 alleles were 46% and 15%, respectively. OBJECTIVE: The aim of this
      study was to evaluate the pharmacokinetic propertiesof pravastatin in healthy
      Mexican mestizo volunteers and to compare them with those in white and Japanese
      populations described in the literature. METHODS: This open-label, uncontrolled
      pilot study of the pharmacokineticproperties of pravastatin was conducted at the
      Division of Pharmacology, Center for Research and Advanced Studies, Mexico City,
      Mexico. Healthy, adult, Mexican volunteers received a single dose of pravastatin
      10 mg PO (tablet). High-performance liquid chromatography was used to determine
      plasma pravastatin concentrations between 15 minutes and 12 hours after dosing.
      RESULTS: Twenty-four subjects (15 women, 9 men; mean age, 30.6 years)participated
      in the study. The mean (SD) Cmax was 9.5 (2.4) ng/mL; Tmax, 0.8 (0.3) hours; AUC0
      infinity 35.7 (19.7) ng/mL - h; t1/2, 2.7 (1.1) hours; and mean residence time,
      3.1 (1.1) hours. One volunteer (4%) had an AUC value that differed substantially
      from the rest of the study population, producing a bimodal distribution of the
      pharmacokinetic parameters. No adverse events were observed or reported during
      the trial. CONCLUSIONS: In this small pilot study of the pharmacokinetic
      properties of pravastatin in Mexican mestizos, AUC was not statistically
      significantly different from previous studies, either in a white or Japanese
      population. However, we did not find the high values reported for Cmax in some
      Japanese subjects carrying recently reported mutations on the pravastatin
      transporter.

PMID- 24672128
TI  - Use of phenytoin for the long-term treatment of partial seizures: Results of a
      survey conducted during the 2004 meeting of the American Academy of Neurology.
AB  - BACKGROUND: Epilepsy is a chronic disorder that typically requires
      lifelongpharmacologic treatment. The choice of an antiepileptic drug (AED),
      therefore, requires careful consideration of efficacy and tolerability. However,
      the majority of patients with new-onset seizures are initially treated by
      physicians in the emergency department (ED) or by non-ED physicians (primary care
      physicians or internists), with phenytoin being the most common AED prescribed
      for initial therapy, and the long-term adverse effects of AEDs are often
      overlooked. OBJECTIVE: The aim of this survey was to examine the perspectives of
      neurologistsand epileptologists concerning initial therapies prescribed by ED
      physicians and non-ED physicians for newly diagnosed partial seizures,
      particularly phenytoin, and the suitability of these therapies for long-term
      management of the disease. METHODS: A computerized survey was conducted during
      the 2004 AmericanAcademy of Neurology meeting. The survey consisted of 10
      questions concerning the use of AEDs in the initial and long-term treatment of
      newly diagnosed partial seizures. RESULTS: The responses of 268 practitioners
      were analyzed. Survey participants indicated that 71% of patients referred to
      them by ED physicians were receiving phenytoin, whereas 59% of patients referred
      to them by non-ED physicians were receiving phenytoin. Seventy-six percent of
      survey participants responded that they would switch a patient having partial
      seizures referred from the ED to another AED. Seventy-eight percent indicated
      that they did not believe that the medications being received by patients with
      newly diagnosed partial seizures in the ED were suitable for long-term epilepsy
      treatment. CONCLUSION: Although appropriate treatment might vary in the acute and
      chronic settings, and phenytoin is used as a primary agent for acute treatment of
      seizures presenting in the ED, the results of the present survey suggest a
      discrepancy between the medications that primary care and ED physicians prescribe
      for newly diagnosed partial seizures and those that specialists prescribe for
      long-term therapy.

PMID- 24672129
TI  - Role of transforming growth factor-beta2 in, and apossible transforming growth
      factor-beta 2 gene polymorphism as a marker of, renal dysfunction in essential
      hypertension: A study in Turkish patients.
AB  - BACKGROUND: Many studies have shown that transforming growth factor(TGF)-beta has
      a major role in renal scarring in many renal diseases and hypertension.
      OBJECTIVES: The primary aim of this study was to investigate both the
      relationship between hypertension and serum and urinary levels of TGF-beta2 (a
      more sensitive isoform for glomeruli than TGF-beta1), and the effects of
      combination therapy with perindopril + indapamide on microalbuminuria, which
      becomes an early indicator of hypertensive benign nephropathy, and serum and
      urinary TGF-beta2 levels in patients with mild to moderate essential
      hypertension. In addition, we examined the possible relationship between TGF
      beta2 gene polymorphism and essential hypertension. METHODS: This study was
      conducted at the Department of Nephrology, Medical Faculty, Gazi University,
      Ankara, Turkey. Patients aged >=18 years with newly diagnosed mild to moderate
      essential hypertension (systolic/diastolic blood pressure [SBP/DBP] >120/>80 mm
      Hg) who had not previously received antihypertensive treatment were included in
      the study. Patients with stage I hypertension received perindopril 2 mg +
      indapamide 0.625 mg (tablet), and patients with stage lI hypertension received
      perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD
      (morning) PO with food for 6 months. Serum and urinary TGF-beta2 and creatinine
      levels and serum and urinary albumin levels were measured before and after
      perindopril + indapamide administration. Amplified DNA fragments of the TGF-beta2
      primer region were screened using amplification refractory mutation system
      polymerase chain reaction analysis, and the number of ACA repeats was confirmed
      by DNA sequencing. Genetic studies were performed using a commercial TGF-beta2
      kit. RESULTS: Forty patients were enrolled in the study, and 38 patients (27
      women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were
      significantly decreased from baseline with perindopril/indapamide (both, P <
      0.001). Microalbuminuria and urinary TGF-beta2 levels also decreased
      significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the
      serum TGF-beta2 level did not change significantly. Three patients, all of whom
      were found to have TGF-beta2 gene mutations, had increased urinary TGF-beta2
      levels despite good blood pressure control. CONCLUSIONS: The results of this
      study in patients with mild to moderate hypertension suggest that, despite good
      clinical control of blood pressure, the persistence of microalbuminuria and high
      urinary TGF-beta2 levels might predict renal impairment. When treating these
      patients, genetic tendencies and possible polymorphisms on the TGF-beta2 locus
      should be kept in mind.

PMID- 24672130
TI  - Effects of zafirlukast on the function of humanpolymorphonuclear neutrophil
      leukocytes in asthmatic patients: A prospective, controlled, in vitro study.
AB  - BACKGROUND: Reactive oxygen species (ROSS) play an important role in the
      pathogenesis of asthma, and oxidative stress contributes to the initiation and
      worsening of inflammatory respiratory disorders (eg, asthma). Thus, antioxidant
      drugs may have a role in reducing or preventing damage in asthma. OBJECTIVE: The
      aim of the study was to investigate the antioxidant effect of zafirlukast, a
      leukotriene receptor antagonist, in asthma. METHODS: This prospective,
      controlled, in vitro study was conducted at KingKhalid University Hospital,
      Riyadh, Saudi Arabia. The generation of ROSS by polymorphonuclear neutrophil
      leukocytes (PMNs) in patients with mild to moderate asthma (forced expiratory
      volume in 1 second [FEVI], >70% of the predicted value) and healthy volunteers
      was assessed using chemiluminescence (CL) with phorbol 12-myristate 13-acetate
      (PMA) and opsonized zymosan (OPZ) in the presence of different concentrations of
      zafirlukast (1.25-60 MUg/mL). The xanthine/xanthine oxidase (X-XOD) reaction was
      used to test the scavenging effect of the drug. RESULTS: Six asthmatic patients
      (4 women, 2 men; mean age, 30.8 years; meanFEVI, 82.5% of the predicted value)
      and 8 healthy volunteers (4 women, 4 men; mean age, 28.8 years) were enrolled. A
      dose-dependent inhibition of the CL response was observed in both groups.
      However, patients with asthma required higher concentrations of zafirlukast to
      achieve an inhibitory effect similar to that in healthy controls. This difference
      was significant at concentrations of 20 to 60 MUg/mL (all, P <= 0.05). When PMNs
      were challenged with OPZ, inhibition was also dose dependent in controls at all
      concentrations (all, P <= 0.05), but the inhibitory effect was not significant in
      the asthmatic patients at any concentration. The difference in the inhibitory
      effect between the 2 groups was significant at 30, 40, and 60 MUg/mL (P < 0.02,
      <0.01, and <0.01, respectively). The mean (SEM) viability of the PMNs in the
      healthy controls was significantly affected only at the highest concentration
      compared with the control saline dose (86.5% [5.8%] vs 97.0% [8.%]; P < 0.05). No
      scavenging effect of zafirlukast was found using the X XOD system. Incubating PMA
      stimulated cells with zafirlukast (5 and 10 MUg/mL) for 10 minutes to 1 hour
      significantly increased the inhibitory effect of the drug by 15% to 46% (all, P <
      0.001). When zafirlukast was tested for reversibility of its inhibitory effect on
      ROS production, its action was found to be irreversible at a concentration of 30
      MUg/mL (P < 0.001) and partially reversible at 60 MUg/mL compared with the
      baseline saline control. CONCLUSIONS: Zafirlukast inhibited ROS generation by
      PMNs in a dose-dependentmanner in asthmatic patients and healthy subjects.
      However, asthmatic patients required much higher concentrations compared with
      controls. The incubation of the stimulated cells with zafirlukast increased the
      inhibitory effect. This finding suggests that the therapeutic effect of
      zafirlukast in asthma may be in part related to its antioxidant action.

PMID- 24672131
TI  - Comparison of on-site and photographic evaluations of the suppressive effects of
      cetirizine, loratadine, and fexofenadine on skin response to histamine
      lontophoresis: A double-blind, crossover study in healthy volunteers.
AB  - BACKGROUND: The standard method used to determine the potency of antihistaminesis
      to assess the degree of suppression of skin response to histamine challenge.
      OBJECTIVES: The aims of this study were to compare the efficacy of 3
      antihistaminesusing a histamine challenge test and the usefulness of on-site
      evaluation with that of photographic evaluation of skin-test reactions. METHODS:
      In this prospective, double-blind, crossover study, healthy volunteerswere given
      cetirizine 5 mg (CTZ-5) and 10 mg (CTZ-10), loratadine 10 mg (LOR), fexofenadine
      60 mg BID (FEX), and placebo (PLC), in a randomly assigned order, with an
      interval of at least 1 week between treatments. Before and 0.5 to 24 hours after
      administration, the areas of flare and wheal induced by histamine iontophoresis
      were measured directly (on site) by 1 evaluator and by another evaluator using
      photographic images on a computer monitor. RESULTS: Ten healthy volunteers (6
      men, 4 women; mean age, 28.2 years[range, 20-39 years]; mean weight, 60.7 kg
      [range, 41-81 kg]) were enrolled. The data from 9 subjects were analyzed; the
      data from 1 subject were omitted because the subject used an over-the-counter
      cold medication containing diphenhydramine several times during the study. By
      both methods, all antihistamines were shown to suppress flare significantly from
      4 to 24 hours after administration. CTZ was most potent in suppressing both flare
      and wheal. For flare, the areas as measured using on-site evaluation were larger
      overall than those measured using photographic evaluation, but the shapes of the
      time-course graphs were similar for both. Overall, the flare area measurements
      started to decrease significantly from baseline values 4 hours after drug
      administration, reached a nadir at 10.5 hours, and remained significantly lower
      compared with baseline values at 24 hours. Comparisons between antihistamines
      showed significant differences in mean flare areas between the 2 doses of CTZ and
      LOR from 8 to 12 hours after administration in both evaluation methods. The wheal
      areas were significantly reduced from baseline values by most of the
      antihistamines 4 to 12 hours after drug administration, reached their lowest
      values at 10.5 hours, and returned to near-baseline values at 24 hours.
      Comparisons with PLC values at each time point, however, showed significant
      differences only for CTZ-5 and CTZ-10 from 4 to 12 hours after administration.
      Comparison between antihistamines showed significant differences in mean flare
      areas between the 2 doses of CTZ and LOR from 8 to 12 hours after administration
      in both evaluation methods. Although the flare areas measured by both methods
      correlated linearly (r = 0.90; P < 0.001), the correlation for wheal areas was
      weaker (r = 0.76; P < 0.001). CONCLUSIONS: In this study in healthy volunteers,
      single doses of CTZ 5 mg and CTZ 10 mg were more potent compared with single-dose
      LOR 10 mg and FEX 60 mg BID in suppressing skin response. Although linear
      correlations were found between skin-response areas, as measured by on-site and
      photographic evaluation, it was difficult to differentiate between wheal and
      flare by photographic evaluation, especially when a typical wheal was suppressed
      to slightly edematous erythema by antihistamines.

PMID- 24672132
TI  - Evaluation of a new five-injection, two-site,intradermal schedule for purified
      chick embryo cell rabies vaccine: A randomized, open-label, active-controlled
      trial in healthy adult volunteers in India.
AB  - BACKGROUND: Human rabies is an ongoing significant public health problem inmany
      developing countries, with India reporting the highest incidence of rabies
      related deaths (~20,000 per year). Many people living in India cannot afford the
      standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are
      administered using a 5-dose regimen developed in Essen, Germany. A potentially
      less expensive intradermal (ID) regimen, based on the Essen regimen, has been
      developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore,
      India. OBJECTIVE: The objective of this study was to compare the immunogenicity
      and local and systemic tolerability of the KIMS-1D regimen with those of the
      standard Essen IM regimen in healthy adult volunteers in India. METHODS: This
      randomized, open-label, active-controlled trial was conductedat the Antirabies
      Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to
      receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1
      mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 ["2-2-2-2-2"]) or the
      Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were
      followed up for 365 days by the treating physician and encouraged to voluntarily
      report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA)
      concentrations were measured before the first injection on day 0 (baseline) and
      on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition
      test. RESULTS: Ninety-one subjects were enrolled and included in the
      tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26
      men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28
      men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were
      pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the
      IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID
      group and none in the IM group; P = 0.026). All of the AEs were transient and
      resolved without the need for medication. All subjects had serum RVNA
      concentrations >=0.5 IU/mL-considered protective by the World Health Organization
      at all follow-up visits. However, the mean RVNA concentrations in the IM group
      were significantly higher compared with those in the ID group from days 14 to 365
      (all, P < 0.001). CONCLUSION: In this study in healthy volunteers, PEP with PCECV
      administered using the KIMS-ID regimen was well tolerated and immunologically
      efficacious for 365 days. Adequate RVNA levels were maintained with the KIMS-ID
      regimen from days 14 to 365, although these levels were significantly lower than
      those achieved in the group receiving the Essen IM regimen (all, P < 0.001).

PMID- 24672133
TI  - Effects of flurbiprofen and tiaprofenic Acid on oxidative stress markers in
      osteoarthritis: A prospective, randomized, open-label, active- and placebo
      controlled trial.
AB  - BACKGROUND: The relationship between oxidative stress and osteoarthritis (OA) has
      been widely investigated. Serum malondialdehyde (MDA), nitric oxide (NO), and
      Cu/Zn superoxide dismutase (SOD) levels are useful markers of oxidative stress.
      Because of the importance of oxidative stress markers in the pathogenesis of OA,
      treatment might involve modification of these markers to control oxidative
      stress. OBJECTIVE: The aim of this study was to compare the effects of 2
      conventionalNSAIDs on markers of oxidative stress in patients with OA of the
      knee. METHODS: This 3-week, prospective, randomized, open-label, active- and
      placebo-controlled study was conducted at the Cerrahpasa Faculty of Medicine,
      Istanbul University, Istanbul, Turkey. Adult patients with clinically and
      radiographically diagnosed moderate OA of the knee who were previously untreated
      were enrolled. Patients were randomly assigned to 1 of 3 treatment groups:
      flurbiprofen 100 mg PO (tablets) BID, tiaprofenic acid 300 mg PO (tablets) BID,
      or placebo tablets BID. Patients were evaluated using clinical assessment and
      laboratory testing before treatment (week 0; baseline) and at the end of week 3.
      The primary end points were the differences in serum MDA, NO, and SOD levels
      versus placebo. Clinical parameters-pain at rest and on motion-were evaluated
      using a 10-cm visual analog scale (0 = no pain to 10 = worst pain imaginable).
      The duration (in minutes) of morning stiffness was recorded by patients, using
      patient diaries. The differences between treatment groups were assessed using
      multivariate analysis. RESULTS: Thirty-nine patients (20 women, 19 men; mean [SD]
      age, 59.0 [11.3]years) were included in the study. Mean serum MDA and NO levels
      were significantly decreased at 3 weeks compared with baseline in the 2 active
      treatment groups (all, P < 0.001); these values remained statistically similar to
      baseline in the placebo group. Serum SOD levels were increased significantly from
      baseline in the 2 active-treatment groups (both, P < 0.001), but not in the
      placebo group. No significant differences in serum MDA and NO levels were found
      between the group receiving flurbiprofen and that receiving tiaprofenic acid.
      Serum SOD levels were significantly higher in the flurbiprofen group compared
      with the tiaprofenic acid and placebo groups (both, P < 0.01). The mean (SD)
      score for pain at rest was significantly lower at 3 weeks compared with baseline
      with flurbiprofen and tiaprofenic acid (both, P < 0.001), but not with placebo.
      The mean score for pain on motion was significantly reduced from baseline values
      only with tiaprofenic acid (P < 0.001). The duration of morning stiffness was
      significantly shorter at 3 weeks compared with baseline in all 3 study groups
      (all, P < 0.001). The mean scores for pain on motion and duration of morning
      stiffness were significantly reduced with tiaprofenic acid compared with placebo
      (both, P < 0.05). The study had some limitations (ie, small sample size, no
      blinding, the short duration of the study, and the weak correlation between serum
      and synovial fluid levels of NO). CONCLUSIONS: In this comparison of the effects
      of 3 weeks of treatment withflurbiprofen 100 mg BID and tiaprofenic acid 300 mg
      BID in patients with knee OA, both treatments effectively reduced serum MDA and
      NO levels compared with placebo. Only tiaprofenic acid significantly improved
      pain at rest and on motion and duration of morning stiffness compared with
      placebo.

PMID- 24672134
TI  - Effects of pantoprazole 20 mg in mildgastroesophageal reflux disease: Once-daily
      treatment in the acute phase, and comparison of on-demand versus continuous
      treatment in the long term.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a chronic disorder,and
      although effective short-term treatment strategies are known, the rate of relapse
      within 1 year is as high as 90% despite successful acute treatment. Consequently,
      most patients with GERD require an effective long-term management strategy to
      achieve adequate symptom control and maintain mucosal healing. OBJECTIVE: The
      present study was undertaken to compare the control ofGERD symptoms during long
      term (24-week) treatment with pantoprazole 20 mg used on-demand or continuously
      in patients with mild GERD after complete relief of acute GERD symptoms. METHODS:
      Patients with endoscopically confirmed Savary/Miller grade 0(normal mucosa) or I
      (patchy red lesions without white coating or with central white coating) GERD
      were enrolled in this multinational, multicenter study comprising 2 phases. In
      the first phase, which was open label, patients were treated with pantoprazole 20
      mg QD for 4 weeks. The presence and intensity of the symptoms of heartburn, acid
      regurgitation, and pain on swallowing were assessed. In the second phase, which
      was an open-label, 24-week, randomized design, only patients completely free of
      GERD symptoms after acute treatment were included. During this phase, on-demand
      treatment with pantoprazole 20 mg was directly compared with continuous
      treatment. The rate of failure to control GERD symptoms after 24 weeks of
      treatment was estimated using the Kaplan-Meier method. Subsequently, the
      difference between treatments (on-demand minus continuous) and its 95% CI were
      calculated, and the on-demand treatment was tested for noninferiority using a
      predefined noninferiority margin of 20%. The mean daily symptom loads were
      compared between the treatment groups using the 1-sided Wilcoxon rank sum test on
      a 5% alpha level. The point estimate of the difference was determined using the
      Hodges-Lehman estimator and the 1-sided 95% CI according to Moses. The number of
      patients unwilling to continue due to insufficient control of heartburn, acid
      regurgitation, and pain on swallowing was analyzed using the Kaplan-Meier (time
      to-event) analysis. Analysis was performed in the same manner as for the rate of
      failure to control GERD symptoms, but the 95% CI was interpreted for statistical
      superiority. RESULTS: A total of 558 patients were enrolled in this study. At the
      end of theacute phase, 82.1% of patients in the per-protocol (PP) population and
      79.1% in the intent-to-treat (ITT) population were relieved of all GERD symptoms,
      and subsequently entered the long-term phase. After 24 weeks of treatment,
      analysis of the failure rates revealed that on-demand treatment was noninferior
      to continuous treatment because the 95% CI was completely below 20% (ITT, 12.1%
      difference [95% CI, -infinity to 18.9%]; PP, 10.1% difference [95% CI, -infinity
      to 17.7%]). The higher perceived mean (SD) daily symptom load in the on-demand
      group (ITT, 1.26 [1.491 vs 0.82 [1.341) was balanced by the reduced tablet intake
      in that group (PP, 0.51 [0.31 ] vs 0.97 [0.11 ] tablets/d; P < 0.001). With
      respect to the rate of patients unwilling to continue treatment, no statistically
      significant difference was observed between the on-demand and continuous groups
      (ITT/PP, 0.95/1.13 vs 0.95/1.26). CONCLUSIONS: In this study of pantoprazole 20
      mg tablets in patients withmild GERD, patients receiving on-demand treatment
      benefited despite their higher symptom load. The similar rates of unwillingness
      to continue treatment in both groups might suggest that patients were satisfied
      with the on-demand treatment strategy. On-demand treatment with pantoprazole 20
      mg was found to be noninferior compared with continuous therapy with regard to
      symptom control. Both on-demand and continuous treatments were well tolerated.

PMID- 24672135
TI  - Comparison of different doses of vancomycin andteicoplanin lock solutions in
      catheters colonized with Staphylococcus epidermidis: An in vitro, blinded,
      antibiotic lock study.
AB  - BACKGROUND: The antibiotic lock (AL) technique is used for sterilization ofthe
      intraluminal surface of catheters. This technique consists of filling a catheter
      lumen with an antibiotic solution and allowing it to dwell for a time sufficient
      to sterilize the device. Glycopeptide antibiotics (vancomycin and teicoplanin)
      are commonly used agents for this purpose. But studies evaluating the different
      dosages of these antibiotics, their optimum concentrations, and duration in AL
      treatment are lacking. OBJECTIVE: The aim of this study was to compare the
      efficacy of differentdoses of vancomycin/saline solution (VSS) and
      teicoplanin/saline solution (TSS) and to establish the optimal dosage and time
      needed to eliminate intraluminal methicillin-resistant Staphylococcus epidermidis
      colonization. METHODS: This in vitro AL study was conducted at the Department of
      Infectious Diseases and Clinical Microbiology, Adnan Menderes University Medical
      Faculty, Aydin, Turkey. Catheters were divided into 2 groups those colonized with
      slime-forming S epidermidis, and those colonized with non-slime-forming S
      epidermidis. In each group, catheters were locked with VSS or TSS at 1-, 3-, and
      5-mg/mL doses. Catheters instilled with saline solution were used as the control
      group. After 12 hours of incubation, the catheters were drained and filled with
      human plasma. Instillation of human plasma or AL solution was alternated every 12
      hours to simulate clinical conditions. Every other day, catheters locked with
      each antibiotic dose or saline were cultured to determine colony count. These
      procedures were maintained until the catheters were sterile. RESULTS: The
      baseline counts of slime-forming and non-slime-forming S epidermidisadhered to 1
      cm segment catheters were 39 * 106 and 32 * 106 colony-forming units,
      respectively. The bacterial count was decreased significantly from baseline on
      the first day after the start of treatment (day 1) (P < 0.001). At the end of day
      7, all catheters treated with antibiotics were sterile. The de creases in
      bacterial count were statistically similar in catheters treated with all doses of
      VSS and TSS. Also, the decrease in intraluminal colonization was statistically
      similar in catheters colonized with slime-forming S epidermidis and non-slime
      forming S epidermidis. CONCLUSION: In this in vitro, blinded AL study, the
      efficacy of vancomycin and teicoplanin lock solutions were similar and sterilized
      the catheters in 7 days, suggesting that the 2 antibiotics might be selected for
      shorter durations compared with those currently recommended for AL treatment in
      catheter-related infections due to methicillin-resistant staphylococci.

PMID- 24672136
TI  - Effects of isoflurane, sevoflurane, and desflurane on platelet function: A
      prospective, randomized, single-blind, in vivo study.
AB  - BACKGROUND: The primary physiologic function of platelets is to facilitate
      hemostasisby aggregation. Volatile anesthetics have been reported to decrease
      platelet aggregation in vivo and in vitro. OBJECTIVE: The aim of this study was
      to investigate the hematologic effectsof the anesthetics isoflurane, sevoflurane,
      and desflurane on hemoglobin (Hb), hematocrit (Hct), platelet count, activated
      partial thromboplastin time (aPTT), prothrombin time (PT), international
      normalized ratio (INR), and platelet aggregation after minor surgery. METHODS:
      Patients aged 20 to 60 years who were scheduled to undergominor surgery and
      American Society of Anesthesiologists physical status P1 or P2 (healthy or mild
      systemic disease) were randomized to 1 of 3 groups: 1 minimum alveolar
      concentration (MAC) of isoflurane, sevoflurane, or desflurane. None of the
      patients received premedication. Anesthesia was induced using IV thiopental 5 to
      6 mg/kg, fentanyl 1 to 2 MUg/kg, and vecuronium 0.1 mg/kg, and maintained with 1
      MAC of isoflurane, sevoflurane, or desflurane in 66% nitrous oxide and 33%
      oxygen. Vecuronium 0.03 mg/kg was given when necessary for muscle relaxation. All
      patients were monitored throughout surgery; isotonic saline was given at a rate
      of 5 mL/kg . h. Hematologic studies were performed preoperatively, 15 minutes
      after intubation, and 1 hour after the end of surgery. Platelet aggregation tests
      were performed in a laboratory using a platelet function analyzer (PFA),
      collagen/epinephrine PFA test cartridges, collagen/adenosine diphosphate PFA test
      cartridges, and PFA trigger solution. RESULTS: This prospective, randomized,
      single-blind, in vivo study was conducted at Gevher Nesibe Teaching Hospital,
      Erciyes University, Kayseri, Turkey. Thirty patients (15 men, 15 women) were
      randomized to the 3 treatment groups (each, n = 10). Hb, Hct, platelet count,
      aPTT, PT, and INR were statistically similar between all 3 groups. The measured
      parameters were not significantly different between the isoflurane and desflurane
      groups at any time point. However, in the sevoflurane group, mean (5D) platelet
      aggregation was significantly delayed 15 minutes after intubation and 1 hour
      after surgery compared with the preoperative values (collagen/epinephrine, 81.70
      [9.85] seconds vs 196.20 [27.84] seconds and 115.40 [25.80] seconds; both, P <
      0.05). CONCLUSIONS: In this study of the effects of isoflurane, sevoflurane, and
      desflurane in patients undergoing minor surgery, clinically relevant
      antithrombotic effects were observed 15 minutes after intubation with all 3
      drugs, although the effects in patients receiving sevoflurane were significantly
      greater compared with those in patients receiving isoflurane and desflurane. The
      antithrombotic effects of isoflurane and desflurane were not continued at 1 hour
      after surgery; however, the inhibitory effects of sevoflurane on platelet
      function were continued at 1 hour after surgery but were significantly decreased
      from levels found at 15 minutes after intubation.

PMID- 24672137
TI  - Comparison of the effects of remifentanil andalfentanil on cardiovascular
      response to nasotracheal intubation: A prospective, randomized, double-blind
      study.
AB  - BACKGROUND: Nasotracheal intubation is often necessary in patients
      undergoingelective or emergency maxillofacial surgery. Previous studies have
      suggested that the increase in blood pressure after nasotracheal intubation is
      significantly greater than the increase after orotracheal intubation. Many drugs,
      including narcotic analgesics, are effective in modifying cardiovascular
      responses to orotracheal intubation. OBJECTIVE: The effects of remifentanil and
      alfentanil on the cardiovascularresponses to nasotracheal intubation were
      compared in healthy patients scheduled to undergo surgery. METHODS: This
      prospective, randomized, double-blind study was conductedat the Department of
      Anesthesiology and Reanimation, Faculty of Medicine, Dicle University,
      Diyarbakir, Turkey. Patients aged 16 to 65 years scheduled to undergo elective
      maxillofacial surgery and who were American Society of Anesthesiologists status I
      or 11 were randomly assigned to receive remifentanil 1 MUg/kg in 10 mL saline
      over 30 seconds followed by an infusion of 0.5 MUg/kg . min, or alfentanil 10
      MUg/kg in 10 mL saline over 30 seconds followed by an infusion of saline.
      Anesthesia was then induced with propofol, cisatracurium, and 1% isoflurane with
      66% nitrous oxide in oxygen. Heart rate (HR) and systolic and diastolic arterial
      pressures (SAP and DAP, respectively) were measured noninvasively at 2 minutes
      before general anesthesia induction (baseline); 2 minutes after induction; and 1,
      3, and 5 minutes after nasotracheal intubation. Patients were monitored for
      cardiac changes using electrocardiography. RESULTS: Forty consecutive patients
      were enrolled in the study. Twenty patients (11 males, 9 females; mean [SD] age,
      27.7 [12.6] years) received remifentanil, and 20 patients (12 males, 8 females;
      mean [SD] age, 31.5 [17.2] years) received alfentanil. Two minutes after
      anesthesia induction, mean (SD) arterial pressures decreased significantly from
      baseline in the remifentanil group (changes, 22 [8]/11 [6] mm Hg) and the
      alfentanil group (changes, 10 [9]/12 [8] mm Hg) (both, P < 0.05). Changes in SAP
      and DAP followed a similar pattern in both groups, but SAP was significantly
      lower in the remifentanil group compared with that in the alfentanil group
      throughout the study period (all, P < 0.05). After 1 minute of intubation, DAP
      was significantly lower in the remifentanil group compared with that in the
      alfentanil group (66 [9] mm Hg vs. 73 [20] mm Hg; P < 0.05). Compared with
      baseline, HR was decreased significantly in both groups throughout the study
      (all, P < 0.05). Except SAP in the alfentanil group, SAP, DAP, and HR were
      increased 1 minute after intubation compared with preintubation values. However,
      SAP, DAP, and HR remained significantly lower compared with baseline values
      throughout the study period in both groups (all, P < 0.05) except DAP at 1 minute
      after incubation in the alfentanil group. Five patients in the remifentanil group
      and 2 patients in the alfentanil group required treatment of hypotension. None of
      the patients in either group required treatment of bradycardia. CONCLUSIONS: In
      this study in healthy surgical patients aged 16 to 65 years, remifentanil 1
      MUg/kg given over 30 seconds, followed by a remifentanil infusion of 0.5 MUg/kg .
      min, was similarly effective compared with alfentanil 10 MUg/kg in attenuating
      the pressor response to nasotracheal intubation, but the incidence of hypotension
      in patients administered remifentanil was high.

PMID- 24672138
TI  - Effects of intravitreal ropivacaine on retinal thickness and integrity in the
      guinea pig.
AB  - BACKGROUND: Retrobulbar anesthesia is widely used for ocular surgery.Ocular
      complications are possible when retrobulbar anesthesia is accidentally injected
      intravitreally. OBJECTIVE: The aim of this study was to determine the relative
      retinal toxicitiesof ropivacaine hydrochloride, a local anesthetic, using various
      concentrations in guinea pigs. METHODS: This randomized, investigator-masked,
      experimental study wasconducted at the Department of Anesthesiology, Dicle
      University, Diyarbakir, Turkey. The right eyes of 18 guinea pigs were assigned to
      1 of 3 treatment groups: 1%, 0.75%, or 0.5% ropivacaine. The right eye of each
      animal was injected intravitreally with 0.1 mL of 1%, 0.75%, or 0.5% ropivacaine.
      The left eye of each animal was injected with a balanced saline solution
      (control). The guinea pigs were euthanized 7 days after injection, and the
      retinal structures were examined using light microscopy. The total thickness of
      each retina was measured using an ocular micrometer. RESULTS: No histologic
      abnormalities were observed in the control eyes.Retinal damage of most of the
      retinal section was seen in the eyes receiving study drug. The eyes injected with
      0.5% ropivacaine had a generally intact appearance, with the exception of some
      atrophy and disorganization. Overall, the eyes injected with 1% ropivacaine had
      significantly more extensive retinal thinning compared with the eyes injected
      with 0.75% or 0.5% ropivacaine (both, P < 0.01). In the eyes injected with 0.75%
      or 1% ropivacaine, disorganization of the structure of the retinal layers and
      atrophy were noted on histopathology. The mean total thicknesses of the retina
      were significantly less in all ropivacaine-treated eyes compared with that in the
      controls (P < 0.001). CONCLUSIONS: In this small experimental study, ropivacaine
      had concentration-dependent toxic effects on guinea pig retinas.

PMID- 24672139
TI  - Farming Systems and Rural Out-Migration in Nang Rong, Thailand and Chitwan
      Valley, Nepal.
AB  - Using data from two post-frontier rural settings, Nang Rong, Thailand (N=2,538)
      and Chitwan Valley, Nepal (N=876), this paper examines agricultural push factors
      determining the outmigration of young people age 15 to 19. We focus on different
      dimensions of migration, including distance and duration. Our study examines a
      wide array of agricultural determinants, each with its own potential effect on
      migration. These determinants include land tenure, crop portfolios, animal
      husbandry activities, and use of farm inputs. We link these proximal causes to
      two underlying mechanisms: risk and amenities. We examine these determinants
      using separate models across settings. Our results indicate that agricultural
      factors are significant determinants of migration in both contexts. However,
      different factors operate in different settings, indicating the importance of
      contextual variation in explaining the manner in which risks and amenities
      influence agricultural determinants of migration.

PMID- 24672140
TI  - Lead Diversification through a Prins-Driven Macrocyclization Strategy:
      Application to C13-Diversified Bryostatin Analogues.
AB  - The design, synthesis, and biological evaluation of a novel class of C13
      diversified bryostatin analogues are described. An innovative and general
      strategy based on a Prins macrocyclization-nucleophilic trapping cascade was used
      to achieve late-stage diversification. In vitro analysis of selected library
      members revealed that modification at the C13 position of the bryostatin scaffold
      can be used as a diversification handle to regulate biological activity.

PMID- 24672141
TI  - The Simultaneous Determination of Six Flame Retardants in Water Samples Using SPE
      Pre-concentration and UHPLC-UV Method.
AB  - Analytical method for the determination of six flame retardants (FRs) from two
      groups was proposed. These groups included the brominated flame retardants (BFRs)
      3,3',5,5'-tetrabromobisphenol A (TBBPA), 1,2,5,6,9,10-hexabromocyclododecane
      (HBCD) and tetrabromophthalic anhydride (TBPA) and triester organophosphate flame
      retardants (OPFRs) tris(2,3-dibromopropyl) phosphate (TBPP), ethylhexyl diphenyl
      phosphate (EHDP) and triphenyl phosphate (TPhP). Reversed phase ultrahigh
      performance liquid chromatography (UHPLC) with a UV detector, different
      chromatographic columns, different mobile phases and gradient elution programmes
      were used to obtain the best separations within the shortest possible time. Solid
      phase extraction (SPE) was examined as a pre-concentration step from distilled
      water. The column with the highest recoveries (the Bond Elut ENV column gave
      recoveries over 70 % for all compounds) was then tested on 1-L blank surface
      water samples. The proposed analytical procedure was applied for the
      determination of FRs in surface water samples. The concentrations of FRs found in
      water samples ranged from 0.03 (TPhP) to 3.10 MUg L-1 (HBCD). Method detection
      limits (MDLs) ranged from 0.008 to 0.518 MUg L-1, and method quantification
      limits (MQLs) ranged from 0.023 to 1.555 MUg L-1 for all compounds.

PMID- 24672142
TI  - Optimal Allocation of Gold Standard Testing under Constrained Availability:
      Application to Assessment of HIV Treatment Failure.
AB  - The World Health Organization (WHO) guidelines for monitoring the effectiveness
      of HIV treatment in resource-limited settings (RLS) are mostly based on clinical
      and immunological markers (e.g., CD4 cell counts). Recent research indicates that
      the guidelines are inadequate and can result in high error rates. Viral load (VL)
      is considered the "gold standard", yet its widespread use is limited by cost and
      infrastructure. In this paper, we propose a diagnostic algorithm that uses
      information from routinely-collected clinical and immunological markers to guide
      a selective use of VL testing for diagnosing HIV treatment failure, under the
      assumption that VL testing is available only at a certain portion of patient
      visits. Our algorithm identifies the patient sub-population, such that the use of
      limited VL testing on them minimizes a pre-defined risk (e.g., misdiagnosis error
      rate). Diagnostic properties of our proposal algorithm are assessed by
      simulations. For illustration, data from the Miriam Hospital Immunology Clinic
      (RI, USA) are analyzed.

PMID- 24672143
TI  - A single centre experience of first "one hundred laparoscopic liver resections".
AB  - Background. Laparoscopic liver resection (LLR) has emerged as an alternative
      procedure to open liver resection in selected patients. The purpose of this study
      was to describe our initial experience of 100 patients undergoing LLR. Methods.
      We analysed a prospectively maintained hepatobiliary database of 100 patients who
      underwent LLR between August 2007 and August 2012. Clinicopathological data were
      reviewed to evaluate surgical outcomes following LLR. Results. The median age was
      64 and median BMI 27. Patients had a liver resection for either malignant lesions
      (n = 74) or benign lesions (n = 26). Commonly performed procedures were
      segmentectomy/metastectomy (n = 55), left lateral sectionectomy (LLS) (n = 26),
      or major hepatectomy (n = 19). Complete LLR was performed in 84 patients, 9 were
      converted to open and 7 hand-assisted. The most common indications were CRLM (n =
      62), followed by hepatic adenoma (n = 9) or hepatocellular carcinoma (n = 7). The
      median operating time was 240 minutes and median blood loss was 250 mL. Major
      postoperative complications occurred in 9 patients. The median length of stay
      (LOS) was 5 days. One patient died within 30 days of liver resection.
      Conclusions. LLR is a safe and oncologically feasible procedure with comparable
      short-term perioperative outcomes to the open approach. However, further studies
      are necessary to determine long-term oncological outcomes. 

PMID- 24672145
TI  - A self-priming, roller-free, miniature, peristaltic pump operable with a single,
      reciprocating actuator.
AB  - We present a design for a miniature self-priming peristaltic pump actuated with a
      single linear actuator, and which can be manufactured using conventional
      materials and methods. The pump is tolerant of bubbles and particles and can pump
      liquids, foams, and gases. We explore designs actuated by a motor (in depth) and
      a shape memory alloy (briefly); and briefly present a manually actuated version.
      The pump consists of a Delrin acetal plastic body with two integrated valves, a
      flexible silicone tube, and an actuator. Pumping is achieved as the forward
      motion of the actuator first closes the upstream valve, and then compresses a
      section of the tube. The increased internal pressure opens a downstream burst
      valve to expel the fluid. Reduced pressure in the pump tube allows the downstream
      valve to close, and removal of actuator force allows the upstream valve and pump
      tube to open, refilling the pump. The motor actuated design offers a linear
      dependence of flow rate on voltage in the range of 1.75-3 V. Flow rate decreases
      from 780 MUl/min with increasing back pressure up to the maximum back pressure of
      48 kPa. At 3 V and minimum back pressure, the pump consumes 90 mW. The shape
      memory alloy actuated design offers a 5-fold size and 4-fold weight reduction
      over the motor design, higher maximum back pressure, and substantial
      insensitivity of flow rate to back pressure at the cost of lower power efficiency
      and flow rate. The manually actuated version is simpler and appropriate for
      applications unconstrained by actuation distance.

PMID- 24672144
TI  - Pancreatic resections in renal failure patients: is it worth the risk?
AB  - Background. Chronic kidney disease affects 20 million US patients, with nearly
      600,000 on dialysis. Long-term survival is limited and the risk of complex
      pancreatic surgery in this group is questionable. Previous studies are limited to
      case reports and small case series and a large database may help determine the
      true risk of pancreatic surgery in this population. Methods. The American College
      of Surgeons National Surgical Quality Improvement Program database was queried
      (2005-2011) for patients who underwent pancreatic resection. Renal failure was
      defined as the clinical condition associated with rapid, steadily increasing
      azotemia (rise in BUN) and increasing creatinine above 3 mg/dL. Operative trends
      and short-term outcomes were reviewed for those with and without renal failure
      (RF). Results. In 18,533 patients, 28 had RF. There was no difference in wound
      infections, neurologic or cardiovascular complications. Compared to non-RF
      patients, those with RF had more unplanned intubation (OR 4.89, 95% CI 1.85
      12.89), bleeding requiring transfusion (OR 3.12, 95% CI 1.37-14.21), septic shock
      (OR 8.86, 95% CI 3.75-20.91), higher 30-day mortality (21.4% versus 2.3%, P <
      0.001) and longer hospital stay (23 versus 12 days, P < 0.001). Conclusions. RF
      patients have much higher morbidity and mortality after pancreatic resections and
      surgeons should consider this before proceeding. 

PMID- 24672146
TI  - Micromechanical PDGF recognition via lab-on-a-disc aptasensor arrays.
AB  - A plug-and-play CD-like platform is used to perform a statistical detection of
      platelet derived growth factor (PDGF) proteins through aptamer-based surface
      functionalization of multiple microcantilever arrays. When PDGF proteins bind to
      aptamer coatings, the cantilevers deflect. The deflection response is monitored
      by optical read-out units from a commercial DVD-ROM device. We report on the use
      of an improved sensing platform which facilitates measurements under continuous
      liquid flow and with temperature control. Also, the mechanical wobbling of the
      DVD-ROM platform has been minimized and the scanning system has been optimized in
      order to detect cantilever deflections in liquid with nanometer scale resolution.
      The capability of the sensing platform is demonstrated by detection of clinically
      relevant concentrations of PDGF proteins. We present statistical measurements on
      100 microcantilevers at different concentrations of PDGF, ranging from 10 nM to
      400 nM. Hereby it is possible to reliably characterize the averaged mechanical
      response of cantilevers as a function of protein concentration.

PMID- 24672147
TI  - Serum soluble triggering receptor expressed on myeloid cells-1 and procalcitonin
      can reflect sepsis severity and predict prognosis: a prospective cohort study.
AB  - OBJECTIVE: To investigate the prognostic significance of serum soluble triggering
      receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal
      probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines,
      and clinical severity scores in patients with sepsis. METHODS: A total of 102
      patients with sepsis were divided into survival group (n = 60) and nonsurvival
      group (n = 42) based on 28-day mortality. Serum levels of biomarkers and
      cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile
      the acute physiology and chronic health evaluation II (APACHE II) and sequential
      organ failure assessment (SOFA) scores were calculated. RESULTS: Serum sTREM-1,
      PCT, and IL-6 levels of patients in the nonsurvival group were significantly
      higher than those in the survival group on day 1 (P < 0.01). The area under a ROC
      curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM
      1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic
      analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the
      independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels
      showed a decrease trend over time in the survival group (P < 0.05). Serum NT-pro
      BNP levels showed the predictive utility from days 3 and 5 (P < 0.05).
      CONCLUSION: In summary, elevated serum sTREM-1 and PCT levels provide superior
      prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT
      levels and SOFA score can offer the best powerful prognostic utility for sepsis
      mortality.

PMID- 24672148
TI  - Impact factor of a scientific journal: Is it a measure of quality of research?

PMID- 24672149
TI  - Monte Carlo-based investigation of water-equivalence of solid phantoms at (137)Cs
      energy.
AB  - Investigation of solid phantom materials such as solid water, virtual water,
      plastic water, RW1, polystyrene, and polymethylmethacrylate (PMMA) for their
      equivalence to liquid water at (137)Cs energy (photon energy of 662 keV) under
      full scatter conditions is carried out using the EGSnrc Monte Carlo code system.
      Monte Carlo-based EGSnrc code system was used in the work to calculate distance
      dependent phantom scatter corrections. The study also includes separation of
      primary and scattered dose components. Monte Carlo simulations are carried out
      using primary particle histories up to 5 * 10(9) to attain less than 0.3%
      statistical uncertainties in the estimation of dose. Water equivalence of various
      solid phantoms such as solid water, virtual water, RW1, PMMA, polystyrene, and
      plastic water materials are investigated at (137)Cs energy under full scatter
      conditions. The investigation reveals that solid water, virtual water, and RW1
      phantoms are water equivalent up to 15 cm from the source. Phantom materials such
      as plastic water, PMMA, and polystyrene phantom materials are water equivalent up
      to 10 cm. At 15 cm from the source, the phantom scatter corrections are 1.035,
      1.050, and 0.949 for the phantoms PMMA, plastic water, and polystyrene,
      respectively. 

PMID- 24672151
TI  - A study on comparison of Gafchromic EBT2 film response under single and
      cumulative exposure conditions.
AB  - Gafchromic films are used as dosimeter for in vivo and in phantom dose
      measurements. The dose response of Gafchromic EBT2 film under single and repeated
      exposure conditions is compared in this study to analyze the usability of
      Gafchromic EBT2 films in cumulative dose measurements. The post-irradiation
      change in response of the film is studied for up to 4 days after irradiation. The
      effect of repeated exposure to scanner light on the response of the film is also
      studied. To check usability of Gafchromic EBT2 films in cumulative dose
      measurements, three EBT2 films were exposed to a daily fraction dose of 100 cGy,
      150 cGy and 200 cGy, respectively, for 4 days. The dose response of the films
      exposed to cumulative irradiation was compared with the dose measured from films
      exposed to the same dose but in a single exposure. It is observed that the post
      irradiation darkening of the film does not saturate and continue to take place
      even 4 days after irradiation. The dose measured from the EBT2 films after 4 days
      from irradiation was around 2% higher than the dose measured from the same films
      at 24 hours post-irradiation. It was also observed that the repeated exposure to
      scanner light does not produce any significant change in the film response. The
      dose response of films exposed to cumulative irradiation agrees with the dose
      response of films exposed to the same dose in a single irradiation with less than
      3% difference. Gafchromic EBT2 films can be used to measure the cumulative dose
      delivered over multiple fractions, when the delivered dose is uniform across the
      film. 

PMID- 24672150
TI  - Dosimetric comparison between IMRT delivery modes: Step-and-shoot, sliding
      window, and volumetric modulated arc therapy - for whole pelvis radiation therapy
      of intermediate-to-high risk prostate adenocarcinoma.
AB  - THIS STUDY WAS PERFORMED TO EVALUATE DOSIMETRIC DIFFERENCES BETWEEN CURRENT
      INTENSITY MODULATED RADIATION THERAPY (IMRT) DELIVERY MODES: Step-and-shoot (SS),
      sliding window (SW), and volumetric modulated arc therapy (VMAT). Plans for 15
      prostate cancer patients with 10 MV photon beams using each IMRT mode were
      generated. Patients had three planning target volumes (PTVs) including prostate,
      prostate plus seminal vesicles, and pelvic lymphatics. Dose volume histograms
      (DVHs) of PTVs and organs at risk (OARs), tumor control probability (TCP) and
      normal tissue complication probabilities (NTCPs), conformation number, and
      monitor units (MUs) used were compared. Statistical analysis was performed using
      the analysis of variance (ANOVA) technique. The TCPs were < 99% with
      insignificant differences among modalities (P > 0.99). Doses to all critical
      structures were higher on average with SW method compared to SS, but
      insignificant. NTCP values were lowest for VMAT in all structures excepting
      bladder. Normal tissue volumes receiving doses in the 20-30 Gy range were reduced
      for VMAT compared to SS. Percentage of MUs required for VMAT to deliver a
      comparable plan to SS and SW was at least 40% less. In conclusion, similar target
      coverage and normal tissue doses were found by the three compared modes and the
      dosimetric differences were small. 

PMID- 24672152
TI  - Study of positional dependence of dose to bladder, pelvic wall and rectal points
      in High-Dose-Rate Brachytherapy in cervical cancer patients.
AB  - The objective of the study is to examine the variation in doses to, Bladder,
      pelvic wall and Rectal Points when a patient is simulated in Supine (S Position)
      and Lithotomy M shaped positions (LM Position), respectively as part of
      Intracavitary Brachytherapy in Cervical Cancer patients. Patients (n = 19) were
      simulated and orthogonal images were taken in S Position and LM Positions on a
      physical simulator. Digital orthogonal X-ray images were transferred to
      Brachyvision Treatment Planning System via Dicom to generate treatment plans.
      Radio opaque dye of 7 ml was injected into the Foley bulb for identification and
      digitization of International Commission on Radiological Units and Measurements
      (ICRU) Bladder point. Pelvic side wall points were marked in accordance with ICRU
      38 recommendations. A Rectal tube containing dummy source marker wire was used to
      identify Rectal Point. Students't-test was used to analyze the results. Doses in
      LM Position were lower and statistically significant when compared to S Position
      for ICRU Bladder Point, pelvic walls and Rectal Point. It was observed that
      movement of applicator could be the reason for the variations in doses between
      the two positions. Bladder, pelvic wall and rectal points systematically
      registered lower doses in LM Position as compared to S Position. 

PMID- 24672153
TI  - Radiation dose estimation of patients undergoing lumbar spine radiography.
AB  - Radiation dose to organs of 100 adult patients undergoing lumbar spine (LS)
      radiography at a University Hospital have been assessed. Free in air kerma
      measurement using an ionization chamber was used for the patient dosimetry. Organ
      and effective dose to the patients were estimated using PCXMC (version 1.5)
      software. The organs that recorded significant dose due to LS radiography were
      lungs, stomach, liver, adrenals, kidney, pancreas, spleen, galbladder, and the
      heart. It was observed that the stomach recorded the highest dose (48.2 +/- 1.2
      MUGy) for LS anteroposterior (AP). The spleen also recorded the highest dose
      (41.2 +/- 0.5 MUGy) for LS lateral (LAT). The mean entrance surface air kerma
      (ESAK) of LS LAT (122.2 MUGy) was approximately twice that of LS AP (76.3 MUGy),
      but the effective dose for both examinations were approximately the same (LS LAT
      = 8.6 MUSv and LS AP = 10.4 MUSv). The overall stochastic health effect of
      radiation to patients due to LS radiography in the University Hospital is
      independent of the projection of the examination (AP or LAT). 

PMID- 24672154
TI  - Evaluation of six scatter correction methods based on spectral analysis in
      (99m)Tc SPECT imaging using SIMIND Monte Carlo simulation.
AB  - Compton-scattered photons included within the photopeak pulse-height window
      result in the degradation of SPECT images both qualitatively and quantitatively.
      The purpose of this study is to evaluate and compare six scatter correction
      methods based on setting the energy windows in (99m)Tc spectrum. SIMIND Monte
      Carlo simulation is used to generate the projection images from a cold-sphere hot
      background phantom. For evaluation of different scatter correction methods, three
      assessment criteria including image contrast, signal-to-noise ratio (SNR) and
      relative noise of the background (RNB) are considered. Except for the dual
      photopeak window (DPW) method, the image contrast of the five cold spheres is
      improved in the range of 2.7-26%. Among methods considered, two methods show a
      nonuniform correction performance. The RNB for all of the scatter correction
      methods is ranged from minimum 0.03 for DPW method to maximum 0.0727 for the
      three energy window (TEW) method using trapezoidal approximation. The TEW method
      using triangular approximation because of ease of implementation, good
      improvement of the image contrast and the SNR for the five cold spheres, and the
      low noise level is proposed as most appropriate correction method. 

PMID- 24672155
TI  - Superparamagnetic iron oxide-C595: Potential MR imaging contrast agents for
      ovarian cancer detection.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs), have played an important
      role in the promotion of image contrast in magnetic resonance imaging modality.
      The objective of present study is describing SPIONs conjugated with C595
      monoclonal antibody (mAb) against MUC1-expressing ovarian cancer (OVCAR3) cell.
      Magnetic resonance imaging parameters of the prepared nanoconjugate was
      investigated in vitro: characterization, cell toxicity, flow cytometry, Prussian
      blue staining, and cellular uptake as well as biodistribution and magnetic
      resonance signal intensities under in vivo conditions were also investigated.
      Magnetic resonance imaging and biodistribution results showed good tumor
      accumulation and detection, no cytotoxicity, and potential selective as anti
      ovarian cancer. In conclusion, based on the findings SPIONs-C595 nanosized-probe
      is potentially, a selective ovarian molecular imaging tool. Further subsequent in
      vivo studies and clinical trials are warranted. 

PMID- 24672156
TI  - Estimation of absorbed dose in clinical radiotherapy linear accelerator beams:
      Effect of ion chamber calibration and long-term stability.
AB  - The measured dose in water at reference point in phantom is a primary parameter
      for planning the treatment monitor units (MU); both in conventional and intensity
      modulated/image guided treatments. Traceability of dose accuracy therefore still
      depends mainly on the calibration factor of the ion chamber/dosimeter provided by
      the accredited Secondary Standard Dosimetry Laboratories (SSDLs), under
      International Atomic Energy Agency (IAEA) network of laboratories. The data
      related to Nd,water calibrations, thermoluminescent dosimetry (TLD) postal dose
      validation, inter-comparison of different dosimeter/electrometers, and validity
      of Nd,water calibrations obtained from different calibration laboratories were
      analyzed to find out the extent of accuracy achievable. Nd,w factors in
      Gray/Coulomb calibrated at IBA, GmBH, Germany showed a mean variation of about
      0.2% increase per year in three Farmer chambers, in three subsequent
      calibrations. Another ion chamber calibrated in different accredited laboratory
      (PTW, Germany) showed consistent Nd,w for 9 years period. The Strontium-90 beta
      check source response indicated long-term stability of the ion chambers within 1%
      for three chambers. Results of IAEA postal TL "dose intercomparison" for three
      photon beams, 6 MV (two) and 15 MV (one), agreed well within our reported doses,
      with mean deviation of 0.03% (SD 0.87%) (n = 9). All the chamber/electrometer
      calibrated by a single SSDL realized absorbed doses in water within 0.13%
      standard deviations. However, about 1-2% differences in absorbed dose estimates
      observed when dosimeters calibrated from different calibration laboratories are
      compared in solid phantoms. Our data therefore imply that the dosimetry level
      maintained for clinical use of linear accelerator photon beams are within
      recommended levels of accuracy, and uncertainties are within reported values. 

PMID- 24672157
TI  - Total body irradiation (TBI): Preliminary experience on clinical implementation.

PMID- 24672158
TI  - From the Editors desk.

PMID- 24672159
TI  - Should mild stimulation be the order of the day?
AB  - Mild stimulation protocols aim to reduce the physical, financial and emotional
      burden associated with the conventional IVF protocol without compromising the
      pregnancy rate. Such protocols help to decrease the complications and the
      discomfort related to the prolonged administration of agonist and large doses of
      gonadotrophins, by limiting the number of oocytes recruited to no more than
      eight. The per cycle pregnancy rates are lower though the cumulative pregnancy
      rate in a year is equivalent. This CPR comes by going through earlier repeat
      cycles. Whether this reduces the physical, emotional or financial burden remains
      a matter of debate. There is need to standardize these protocol and do more
      trials to compare the two effectively. Till such time there is a clear benefit
      above the conventional protocol it will not be the protocol of choice with most
      physicians. 

PMID- 24672160
TI  - Luteinizing hormone and follicle stimulating hormone synergy: A review of role in
      controlled ovarian hyper-stimulation.
AB  - Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH)
      stimulates normal follicular growth and ovulation. FSH is frequently used in
      assisted reproductive technology (ART). Recent studies have facilitated better
      understanding on the complementary role of the LH to FSH in regulation of the
      follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in
      stimulation and its importance in advanced aged patients has been a topic of
      discussion among medical fraternity. Though the administration of exogenous LH
      with FSH is obligatory for controlled ovarian stimulation in patients with
      hypogonadotropic hypogonadism, there is still a paucity of information of its
      usage in other patient population. In this review we looked in to the multiple
      roles that LH plays complementary to FSH to better understand the LH requirement
      in patients undergoing ART. 

PMID- 24672161
TI  - Assisted reproductive technology in India: A 3 year retrospective data analysis.
AB  - Assisted reproductive technology (ART) has grown by leaps and bounds in the last
      few years. India has one of the highest growths in the ART centers and the number
      of ART cycles performed every year. Very soon India will be the leader in the
      world of ART in terms of a number of cycles. With the advances of technology and
      availability of techniques even in tier II and tier III cities our country, the
      results still vary dramatically. There is no standardization of protocols and
      reporting is very inadequate. Furthermore, there are only ART guidelines and no
      law still exists. Our first and the biggest challenge is to document the
      tremendous work being done in India and on the basis of analysis of this work, a
      proper registry can be made and guidance given to all on standardization and
      improvement. This is the 8(th) edition of National ART Registry of India being
      presented and analyzed. 

PMID- 24672162
TI  - Semen preparation techniques in intrauterine insemination: A comparison of non
      temperature and temperature controlled centrifugation in cases of unexplained
      infertility.
AB  - AIM: The aim of the following study is to compare pregnancy rates between the use
      of non-temperature and temperature controlled centrifugation on semen preparation
      technique in intrauterine insemination. MATERIALS AND METHODS: The retrospective
      study was conducted on 671 patients of idiopathic infertility who underwent
      homologous artificial insemination at Fertility Research Center from the period
      of January 2007 to September 2012. The couples were randomized into two groups
      namely, Group A-patients (n = 303) being treated with sperm prepared by using non
      temperature controlled centrifuge and Group B-Patients (n = 368) being treated
      with sperm prepared by temperature (37 degrees C) controlled centrifuge. RESULTS
      AND CONCLUSION: The clinical pregnancy rate Group A was 13.86% and Group B was
      12.77%. The clinical pregnancy fetal loss rate between the two groups was 38% and
      42% respectively. The delivery rate per transfer was 62% and 58% respectively. No
      statistically significant difference was found between these two groups.

PMID- 24672163
TI  - Predictive value of early serum beta-human chorionic gonadotrophin for the
      successful outcome in women undergoing in vitro fertilization.
AB  - AIMS: Pregnancies achieved by in vitro fertilization (IVF) are at increased risk
      of adverse outcome. The main objective of this study was to evaluate the
      predictive value of beta-human chorionic gonadotrophin (beta-HCG) and age of the
      patient for the successful outcome in IVF. MATERIALS AND METHODS: A retrospective
      study was done in 139 pregnancies after IVF at single IVF center from June 2007
      to July 2012. The age of the patient and initial serum values of beta-HCG on day
      14 of embryo transfer were correlated with ongoing pregnancy (>12 weeks
      gestation). RESULTS: The beta-HCG level on day 14 of more than 347 mIU/ml has a
      sensitivity of 72.2% and specificity of 73.6% in prediction of pregnancy beyond
      12 weeks period of gestation. Positive likelihood ratio (LR) is 2.74 and negative
      LR is 0.37, (receiver operating characteristic area = 0.79). DISCUSSION: In IVF
      cycles, there is a lot of stress on the couples while the cycle is going on.
      There was a positive correlation between the higher values of early serum beta
      HCG levels and ongoing pregnancy. Hence, it can be used as an independent
      predictor of a successful outcome of IVF cycle. CONCLUSION: We concluded from our
      study that early serum beta-HCG can be used as a predictor of a successful
      outcome in IVF.

PMID- 24672164
TI  - Calcium gluconate infusion is as effective as the vascular endothelial growth
      factor antagonist cabergoline for the prevention of ovarian hyperstimulation
      syndrome.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and
      potentially life-threatening disease process, which may occur in healthy young
      women undergoing controlled ovarian hyperstimulation for assisted reproduction.
      As the treatment is largely empirical, prevention forms the mainstay of
      management. OBJECTIVE: The present study was aimed to evaluate the effectiveness
      of intravenous (IV) calcium gluconate infusion in comparison to the dopamine
      agonist cabergoline (Cb2) in preventing OHSS in high risk patients undergoing
      assisted reproductive technique cycles. MATERIALS AND METHODS: It was a
      comparative study wherein the 202 high risk patients undergoing in vitro
      fertilization over a period of 18 months after meeting the strict inclusion and
      the exclusion criteria, were randomly divided into two groups (98 subjects in
      Group I and 104 in Group II). Women in Group I were administered IV calcium
      gluconate while the remaining 104 received the dopamine agonist Cb2. The 104
      patients belonging to Group II were started Cb2 0.5 mg/day from the day of
      ovulation trigger and continued until the next 8 days while the 98 high risk
      patients from Group I were infused with 10 ml of 10% calcium gluconate solution
      in 200 ml physiologic saline within 30 min of ovum pick up and continued
      thereafter on day 1, day 2 and day 3. RESULTS: The occurrence of OHSS was seen in
      only nine patients (in the calcium infusion group, when compared with 16 patients
      (9.2% vs. 15.4%) who were administered Cb2, but it was not statistically
      significant. However, only one had severe OHSS in Group I, whereas two women were
      diagnosed as severe OHSS belonging to the Cb2 arm. CONCLUSION: Our results
      document that calcium infusion can effectively prevent severe OHSS and decreases
      OHSS occurrence rates when used for high-risk patients, but does not suggest its
      superiority over Cb2. With comparable success rates, either of them can be
      employed as a preventive strategy for OHSS.

PMID- 24672165
TI  - Melatonin and its correlation with testosterone in polycystic ovarian syndrome.
AB  - CONTEXT: Polycystic ovarian syndrome (PCOS) is considered to be the most common
      endocrine disorder affecting women. Melatonin, a small lipophilic indoleamine,
      and reproductive hormones may be interrelated. Melatonin influences sex steroid
      production at different stages of ovarian follicular maturation as melatonin
      receptors have been demonstrated at multiple sites in ovary and in
      intrafollicular fluid. It plays role as an antioxidant and free radical scavanger
      which protects follicles from oxidative stress, rescuing them from atresia,
      leading to complete follicular maturation and ovulation. AIMS: To study the role
      of melatonin in PCOS and to investigate its correlation with testosterone in
      patients suffering from PCOS. SETTINGS AND DESIGN: A total of 50 women with PCOS
      (Rotterdam criteria, 2003) and 50 age and weight matched healthy controls were
      selected and serum melatonin estimation was done in both the groups and
      correlated with serum total testosterone levels. MATERIALS AND METHODS: In a case
      control study, detailed history, clinical examination and hormonal evaluation
      [basal levels of leutinizing hormone, follicle-stimulating hormone, thyroid
      stimulating hormone, prolactin, insulin, total testosterone, progesterone and
      melatonin] were carried out in all the participants including both cases and
      controls. For melatonin estimation, blood samples were collected between 12:00 am
      and 04:00 am on day 2(nd) of menstrual cycle and analyzed by using commercially
      available enzyme-linked immunosorbent assay kit. STATISTICAL ANALYSIS: Student's
      t-test was used to compare the significant difference in mean values between
      cases and control groups. Chi-square test was used to test the significant
      association between the qualitative variables. Linear correlation coefficient and
      regression analysis were done to see the amount and direction of relationship
      between quantitative variables. RESULTS: The mean melatonin level was observed to
      be significantly increased in patients (63.27 +/- 10.97 pg/mL) than in controls
      (32.51 +/- 7.55 pg/mL). Melatonin was found to be raised in all the cases of PCOS
      (above cut-off value of >=45 pg/mL, P < 0.001). Total testosterone level was also
      raised in 72% of patients. Melatonin levels were found to be positively
      associated with increased testosterone (P < 0.001). In regression analysis using
      melatonin as dependent variable and testosterone as an independent variable, the
      value of R2 Chi 100 (percent variation) was found to be 72.1%. CONCLUSIONS: Women
      with PCOS have significantly raised serum melatonin levels and hyperandrogenemia
      along with increased number of atretic follicles. Further studies are required to
      establish a definite role of melatonin in PCOS cases with disturbed hormonal
      milieu. This could open up the way for therapeutic role of melatonin in treatment
      of patients suffering from PCOS.

PMID- 24672166
TI  - The combined use of antimullerian hormone and age to predict the ovarian response
      to controlled ovarian hyperstimulation in poor responders: A novel approach.
AB  - CONTEXT: Reduced ovarian response to stimulation represents one of the most
      intractable problems in infertility treatment. As failed cycle can cause
      considerable amount of emotional and economical loss, there are various attempts
      made to predict ovarian response. AIMS: To evaluate different factors influencing
      outcome of assisted reproduction in women with predicted reduced response
      (antimullerian hormone between 1 and 5 pmol/L) and to develop a model using of
      AMH and age to predict the number of oocytes in poor responders. SETTINGS AND
      DESIGN: Retrospective study in a teaching hospital. MATERIALS AND METHODS: We
      analyzed 85 cycles (57 women) with predicted reduced response with serum AMH
      value between 1 and 5 pmol/L. Standard ovarian stimulation protocol was used.
      Primary outcome measures were clinical pregnancy rates and oocytes retrieved.
      STATISTICAL ANALYSIS USED: Data were analyzed using Microsoft excel and MetlabR
      software. RESULTS: Clinical pregnancy rate/ET was 20.33%, in this group. AMH and
      age was analyzed using linear regression model which produced an equation to give
      predicted oocyte count if AMH and age are known. (Oocytes = age * (-beta) + Serum
      AMH * alpha) (Constant beta=0.0102 and alpha = 1.0407). CONCLUSIONS: Combined use
      of serum AMH and age to predict ovarian response within reduced responder group
      should be further evaluated. For first time, we suggested combining both factors
      to predict ovarian response using a simple equation which allow developing
      tailored strategy.

PMID- 24672167
TI  - Anesthetic management for oocyte retrieval: An exploratory analysis comparing
      outcome in in vitro fertilization cycles with and without pre-implantation
      genetic diagnosis.
AB  - PURPOSE: To date, there has been no comparison of outcomes in women undergoing
      anesthesia for in vitro fertilization (IVF) oocyte retrieval for the purpose of
      pre-implantation genetic diagnosis (PGD) because of their or their partner's
      genetic disease relative to the outcome in women requiring IVF because of
      fertility issues. MATERIALS AND METHODS: A prospective observational study,
      wherein all demographic and anesthetic management data were collected from IVF
      and PGD units' records for a 6-month period. Descriptive analyses and parametric
      tests were employed. RESULTS: There were 307 cases IVF and 76 cases PGD: most
      (97.4% and 99.7%, respectively) received general anesthesia with propofol and
      fentanyl +/- dipyrone (90.5% and 93.3%, respectively) with no adverse effects.
      The only statistically significant difference between IVF and PGD groups that was
      potentially clinically significant was post-procedure recovery time (23.0 +/-
      20.4 vs. 29.4 +/- 35.8 min, respectively; P < 0.0001), but is explainable as
      greater caution by Anesthesiologists for higher-risk PGD cases having autosomal
      dominant diseases that may impact anesthesia management (myotonic dystrophy,
      neurofibromatosis, Marfan's); two of these cases also recovered in the general
      post-anesthesia care unit, as a precaution for early diagnosis and treatment of
      potential post-procedural complication. CONCLUSIONS: Results of this first-ever
      survey of anesthesia for PGD compared with IVF cases imply that propofol-and
      fentanyl-based anesthesia is safe and can be recommended, bearing in mind that
      with patients who have autosomal dominant diseases impacting anesthetic
      management it is prudent to be more cautious post-recovery.

PMID- 24672168
TI  - Reproductive parameters and oxidative stress status of male rats fed with low and
      high salt diet.
AB  - BACKGROUND: Deficiency of minerals and micronutrients has been reported to impair
      the process of spermatogenesis. Historically, salt has been used by women on
      their husbands to increase their libido, however, the role of salt diet on sperm
      parameters are yet to be ascertained. AIM: The present study was designed to
      determine the effect of low and high salt diet on sperm parameters, oxidative
      status and reproductive hormone levels of male rats. MATERIALS AND METHODS: A
      total of 18 rats were divided into three groups: Group I: (control) received 0.3%
      salt diet, Group II: low salt (received 0.14% salt diet) and Group III: high salt
      (received 8% salt diet). All animals were treated for 6 weeks; after which
      epididymal sperm parameters; oxidative stress markers (malondialdehyde,
      glutathione, catalase and superoxide dismutase) in the testes and epididymal
      tissues, as well as follicle stimulating hormone (FSH), luteinizing hormone (LH)
      and testosterone levels were determined. RESULTS: The results showed decreased
      sperm count in the low salt diet rats while increased sperm count was observed in
      the high salt diet treated rats. Both low salt and high salt diet fed rats
      exhibited increased abnormal sperm cells and increased epididymal oxidative
      stress when compared with their respective control. FSH and testosterone levels
      were increased in the high salt fed rats while LH level was decreased when
      compared with the control values. CONCLUSION: This study suggests that both low
      and high salt diet play a negative role in the fertility of male rats.

PMID- 24672169
TI  - Diagnosis and management of cervical ectopic pregnancy.
AB  - Cervical ectopic pregnancy (CP) is a rare condition with an incidence of less
      than 0.1% of all ectopic pregnancies. It is associated with a high morbidity and
      mortality potential. Timely intervention is required to preserve fertility and
      avoid the need for a hysterectomy. A case of CP is reported and the challenges in
      the diagnosis and management are discussed. 

PMID- 24672170
TI  - A rare case of Turner's syndrome presenting with Mullerian agenesis.
AB  - Turner's syndrome also called as Ullrich Turner's syndrome, is a disease of
      unclear pathogenesis characterized by complete or partial absence of one sex
      chromosome, with or without cell line mosaicism in a phenotypic female with short
      stature. Various anomalies result in a constellation of features, of which the
      most disturbing is primary amenorrhea due to gonadal dysgenesis. Hormone therapy
      in these patients can often result in successful menstruation, and scope for
      subsequent pregnancy because of anatomically normal uterus and vagina. Coexisting
      Mullerian agenesis in these patients can jeopardize the chances of future
      pregnancy as they have associated structural abnormalities of the uterus and
      vagina. We report a rare case of middle-aged female with Turner's syndrome and
      Mullerian agenesis having absent secondary sexual characters and missing uterus
      with incompletely formed vagina. 

PMID- 24672171
TI  - State of the globe: non-fermenting gram-negative bacilli challenges and potential
      solutions.

PMID- 24672172
TI  - The importance of accuracy in diagnosis of positive malaria cases in a country
      progressing towards malaria elimination.
AB  - BACKGROUND: With Sri Lanka aiming towards malaria elimination by 2015, the
      National Anti Malaria Campaign has stressed on the importance of identification
      of the species of Plasmodium either by examination of stained blood smears for
      malaria parasites or by Rapid Diagnostic Tests for malaria antigens before the
      initiation of treatment. This study aims at confirmation of the accuracy of
      clinical and/or microscopical malaria diagnosis using serology. MATERIALS AND
      METHODS: Study population comprised 51 individuals diagnosed with malaria either
      microscopically or clinically during the first half of 2011. ELISA for detection
      of the two significant blood antigens (AMA-1 and MSP1-19) was carried out in
      these individuals, 14-28 days after being diagnosed as being positive for malaria
      microscopically. RESULTS: ELISA confirmed the microscopic diagnosis in all 47 of
      the patients including two mixed infections which flagged positive for both
      parasite antigens. However, four individuals diagnosed clinically as being
      positive for P. vivax by Health Care Providers were negative for malaria
      antibodies by ELISA. CONCLUSIONS: With 175 cases of malaria reported in 2011, a
      formidable challenge exists to diagnose malaria positive blood smears due to the
      large number of negative blood smears being seen daily. After routine cross
      checking of positive slides, it is heartening to note that there were no false
      positives detected through serological assays amongst patients who were diagnosed
      as malaria positive by microscopy. Presumptive treatment of febrile patients with
      anti-malarials can lead to waste of resources and adversely impact the condition
      of the patient if the fever is not due to malaria.

PMID- 24672173
TI  - The Plasmodium falciparum Antigen MB2 Induces Interferon-gamma and Interleukin-10
      Responses in Adults in Malaria Endemic Areas of Western Kenya.
AB  - BACKGROUND: MB2 is a novel Plasmodium falciparum antigen of unknown function
      expressed in pre-erythrocytic and blood stages of infection in the human host.
      Interferon-gamma (IFN-gamma) and interleukin (IL)-10 responses to other P.
      falciparum antigens have been associated with protection from clinical malaria,
      but these responses have not been studied for MB2. The present study was
      undertaken to characterize IFN-gamma and IL-10 responses to P. falciparum MB2
      antigen in adults living in areas of differing malaria transmission in Western
      Kenya. MATERIALS AND METHODS: Cytokine responses to two 9-mer MB2 peptides
      predicted to be human leukocyte antigen (HLA) class I restricted T-cell epitopes
      were measured by enzyme-linked immunosorbent assay (ELISA) (IFN-gamma and IL-10)
      and enzyme-linked immunosorbent spot (ELISPOT) (IFN-gamma) in adults (n = 228) in
      areas of unstable and stable malaria transmission. HLA class I restriction of
      responses was assessed in a sub-group of the study population. RESULTS: IFN-gamma
      and IL-10 responses to MB2 peptides by ELISA were observed in both sites with no
      significant difference in prevalence (IFN-gamma, unstable transmission area,
      18.8%, stable transmission area, 27.5%, P = 0.33; IL-10, unstable transmission
      area, 22.5%, stable transmission area, 25.0%, P = 0.78). Prevalence of IFN-gamma
      responses by ELISPOT was also similar in both areas (unstable, 10.8%, stable,
      10.9%, P = 0.98). Neither IFN-gamma nor IL-10 responses showed evidence of HLA
      class I restriction. CONCLUSIONS: MB2 induces IFN-gamma and IL-10 responses in
      adults living in both stable and unstable malaria transmission areas. Future
      studies should assess if these responses are associated with protection from
      clinical malaria.

PMID- 24672174
TI  - Prevalence and risk factors associated with pediculosis capitis in an
      impoverished urban community in lima, peru.
AB  - BACKGROUND: Pediculosis capitis is a ubiquitous parasitic skin disease associated
      with intense pruritus of the scalp. In developing countries it frequently affects
      children and adults, but epidemiological data at the community level are rare.
      OBJECTIVES: To assess prevalence and risk factors associated with pediculosis
      capitis in a resource-poor community in Lima, Peru. MATERIALS AND METHODS: In
      total, 736 persons living in 199 households in a circumscribed neighbourhood were
      examined for head lice and nits by visual inspection. At the same time, socio
      demographic data were collected using a structured questionnaire. Variables
      associated with pediculosis were identified by performing a bivariate analysis,
      followed by a multivariate logistic regression analysis. RESULTS: Prevalence of
      pediculosis capitis was 9.1% (95% confidence interval (CI): 7.0-11.2 %) in the
      general population and 19.9% (CI: 15.4-24.4%) in children <=15 years of age.
      Multivariate analysis showed that pediculosis capitis was significantly
      associated with age <= 15 years (OR: 16.85; CI:7.42-38.24), female sex (OR: 2.84;
      CI: 1.58-5.12), household size of >4 persons (OR: 1.98; CI: 1.11-3.55), low
      quality of house construction material (OR:2.22; CI: 1.20-4.12), and presence of
      animals in the household (OR: 1.94; CI: 1.11-3.39). CONCLUSION: Pediculosis
      capitis was a very common disease in the studied community in Lima, Peru. Our
      logistic regression analysis affirms that young age is the most important risk
      factor for pediculosis capitis. Moreover, female sex, large household size,
      living in wooden houses and the presence of animals were identified as being
      significantly associated with head lice infestation.

PMID- 24672175
TI  - Nonfermenting Gram-negative Bacilli other than Pseudomonas aeruginosa and
      Acinetobacter Spp. Causing Respiratory Tract Infections in a Tertiary Care
      Center.
AB  - BACKGROUND: Nonfermenting gram-negative bacilli have emerged as important
      healthcare-associated pathogens. It is important to correctly identify all
      clinically significant nonfermenting gram-negative bacilli considering the
      intrinsic multidrug resistance exhibited by these bacteria. MATERIALS AND
      METHODS: A retrospective study was undertaken to identify the various
      nonfermenting gram-negative bacilli other than Pseudomonas aeruginosa and
      Acinetobacter spp. isolated from respiratory samples (n = 9363), to understand
      their clinical relevance and to analyze their antibiotic susceptibility pattern.
      RESULTS: Nonfermenting gram-negative bacilli were isolated from 830 (16.4%)
      samples showing significant growth. Thirty-three (4%) isolates constituted
      nonfermenting gram-negative bacilli other than P. aeruginosa and Acinetobacter
      spp. Stenotrophomonas maltophilia (15, 45.5%) was the most common isolate
      followed by Burkholderia cepacia (4, 12.1%), Sphingomonas paucimobilis (3, 9.1%),
      and Achromobacter xylosoxidans (3, 9.1%). On the basis of clinicomicrobiological
      correlation, pathogenicity was observed in 69.7% (n = 23) isolates. Timely and
      correct treatment resulted in clinical improvement in 87.9% cases. CONCLUSION:
      Any nonfermenting gram-negative bacilli isolated from respiratory tract infection
      should not be ignored as mere contaminant, but correlated clinically for its
      pathogenic potential and identified using standard methods so as to institute
      appropriate and timely antibiotic coverage.

PMID- 24672176
TI  - Prevalence and distribution of schistosomiasis in afder and gode zone of somali
      region, ethiopia.
AB  - BACKGROUND: There is no recent information about the prevalence and distribution
      of schistosomiasis in the Somali national regional state of Ethiopia. Ethiopia
      launched the national integrated neglected tropical diseases (NTDs) Master Plan
      in June 2013. The Master Plan identified mapping NTDs as a prerequisite for
      launching control programs. Therefore it is important to understand the
      prevalence and distribution of schistosomiasis in respective regions. MATERIALS
      AND METHODS: From February to March 2011, a cross-sectional survey was done in
      school-aged children from six districts of Afder Gode zone. Urine samples were
      collected and examined for ova of Schistosoma haematobium using the sedimentation
      technique and stool samples were collected and examined for S. mansoni using the
      Kato-Katz technique. A semistructured questionnaire was used to collect
      sociodemographic characteristics of the participants. RESULTS: Of the 523
      children, 513 (98%) of them participated in the study. The prevalence of S.
      haematobium was 16.0% (95% confidence interval (CI); 12.8-19.2). The rate of the
      disease was not uniform across the various six communities studied (x(2) = 208.8,
      P < 0.0001). Musthail district had the highest prevalence with 64.2% (95% CI;
      60.0-68.3) followed by Kelafo with 11.8% (95% CI; 9.0-14.6). No infections of S.
      mansoni were found in these settings. There was no difference in the prevalence
      of infection across age groups. Boys were more likely to be infected by S.
      haematobium than girls (odds ratio = 1.68; 95% CI: 1.1-2.7). CONCLUSION: S.
      haematobium infection is prevalent in the region with varying distribution across
      the districts. According to the World Health Organization, mass drug
      administration should be considered in some of the districts.

PMID- 24672177
TI  - Rapid detection of malaria parasite by toluidine blue method: a new staining
      method.
AB  - BACKGROUND: Malaria is a commonest mosquito-borne infectious disease worldwide.
      Early identification and management of malaria prevents complications and
      mortality. Identification of the malaria mainly relies on detection of the
      parasite on blood smears. The present study was conducted to compare Toluidine
      blue method with Leishman method for detection of malaria parasite and also to
      study the efficacy and advantages of using Toluidine blue method. MATERIALS AND
      METHODS: In 540 consecutive patients with clinical suspicion of malaria,
      peripheral smears were prepared. Smears were processed for both conventional
      Leishman method and Toluidine blue method simultaneously. The significance of
      Toluidine blue method over Leishman method was analyzed using Chi-square (chi(2))
      test. RESULTS: Out of 540 smears, 28.3% (153/540) were positive for malaria
      parasite on conventional Leishman method, while the smear positivity was more by
      Toluidine blue method to 33.3% (180/540) [P value < 0.01]. The remaining 66.67%
      (360/540) were negative by both Toluidine blue method and conventional Leishman
      method. CONCLUSION: The Toluidine blue method is simple, rapid, inexpensive, and
      easily available. The implementation of Toluidine blue method clearly improves
      microscopic detection of malaria parasite and can be a useful contribution to
      routine hematology even at rural health sectors.

PMID- 24672178
TI  - Infection control and practice of standard precautions among healthcare workers
      in northern Nigeria.
AB  - BACKGROUND: Healthcare-associated infections (HAIs) have been reported to be a
      serious problem in the healthcare services as they are common causes of illness
      and mortality among hospitalized patients including healthcare workers (HCWs).
      Compliance with these standard precautions has been shown to reduce the risk of
      exposure to blood and body fluids. AIMS: This study therefore assesses the level
      of knowledge and compliance with standard precautions by the various cadre of
      HCWs and the factors influencing compliance in hospital environment in Nasarawa
      State, Northern Nigeria. SETTINGS AND DESIGN: Nasarawa State has a current human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) prevalence
      rate of 10.0%, which was higher than most states in Nigeria with a high level of
      illiteracy and ignorance. Majority of the people reside in the rural areas while
      a few are found in the towns, informal settlements with no direct access to
      healthcare facilities are common. MATERIALS AND METHODS: This study is an
      analytical, cross-sectional study. Proportional sampling technique was used to
      obtain a representative sample and a structured self-administered questionnaire
      was used to collect relevant information from the healthcare providers working in
      Nasarawa State from January to February 2009. STATISTICAL ANALYSIS USED: To
      describe patient characteristics, we calculated proportions and medians. For
      categorical variables, we compared proportions using chi-square tests. A logistic
      regression model was produced with infection control as outcome variable to
      identify associated factors. RESULTS: A total of 421 HCWs were interviewed,
      Majority (77.9%) correctly describe universal precaution and infection control
      with 19.2, 19.2, and 28.0%, respectively unable to recognize vaccination,
      postexposure prophylaxis, and surveillance for emerging diseases as standard
      precaution for infection control. About 70.1% usually wear gloves before handling
      patients or patients' care products, 12.6% reported wash their hand before
      wearing the gloves, 10.7% washed hands after removal of gloves, and 72.4% changed
      gloves after each patient. Only 3.3% had a sharp disposal system in their various
      workplaces. Majority (98.6%) of the respondents reported that the major reason
      for noncompliance to universal precautions is the nonavailability of the
      equipments. There was a statistically significant difference in the practice of
      standard precaution among those that were exposed to blood products and body
      fluid compared to those that had not been exposed in the last 6 months (chi(2) =
      3.96, P = 0.03), public healthcare providers when compared to private health
      workers (chi(2) = 22.32, P = 0.001), among those working in secondary and
      tertiary facilities compared to primary healthcare centers (chi(2) = 14.64, P =
      0.001) and urban areas when compared to rural areas (chi(2) = 4.06, P = 0.02).
      The only predictor of practice of standard precaution was exposure to blood and
      body fluid in the last 6 months odds ratio (OR) = 4.56 (confidence interval (CI)
      = 1.00-21.28). CONCLUSIONS: This study implies that inadequate workers' knowledge
      and environment related problems, including the lack of protective materials and
      other equipments and utilities required to ensure safety of HCWs is a crucial
      issue that need urgent attention. Institution of a surveillance system for
      hospital acquired infection to improve consistent use of standard precautions
      among health workers is recommended in Nigeria and other low income countries in
      Africa.

PMID- 24672179
TI  - Study of opportunistic intestinal parasitic infections in human immunodeficiency
      virus/acquired immunodeficiency syndrome patients.
AB  - INTRODUCTION: Intestinal parasites predominantly coccidian parasites are a common
      cause for diarrhea in human immunodeficiency virus (HIV)-positive patients.
      MATERIALS AND METHODS: The study was conducted during January 2009-December 2010.
      A total of 1,088 stool samples from 544 seropositive HIV positive cases were
      examined microscopically for ova and cyst using wet mount preparations and
      stained smears. Out of 544 patients, 343 had prolonged diarrhea for more than 4
      weeks, 57 had acute diarrhea of lesser than 7 days and 144 were asymptomatic
      cases who attended out-patient department; included in this study after taking
      consent from patients. Enteric pathogens were detected in 274 (50.36%) of the 544
      patients. RESULTS AND CONCLUSIONS: The parasites identified were Cryptosporidium
      (135), Isospora belli (42), Cyclospora (12), Microsporidia (02), Entamoeba
      histolytica (49), Hookworm (34). Intestinal parasites in chronic diarrhea were
      significantly higher than the acute diarrhea (63.05% vs. 7.35%; P < 0.05).
      Parasitic pathogens were frequently associated with HIV-positive patients with
      diarrhea in Western India. Stools of all HIV-positive patients with diarrhea
      should thoroughly be investigated to identify etiologic agents for proper
      management. MATERIALS AND METHODS: The study was conducted during January 2009
      December 2010. A total of 1,088 stool samples from 544 seropositive HIV positive
      cases were examined microscopically for ova and cyst using wet mount preparations
      and stained smears. Out of 544 patients, 343 had prolonged diarrhea for more than
      4 weeks, 57 had acute diarrhea of lesser than 7 days and 144 were asymptomatic
      cases who attended out-patient department; included in this study after taking
      consent from patients. Enteric pathogens were detected in 274 (50.36%) of the 544
      patients. RESULTS AND CONCLUSIONS: The parasites identified were Cryptosporidium
      (135), Isospora belli (42), Cyclospora (12), Microsporidia (02), Entamoeba
      histolytica (49), Hookworm (34). Intestinal parasites in chronic diarrhea were
      significantly higher than the acute diarrhea (63.05% vs. 7.35%; P > 0.05).
      Parasitic pathogens were frequently associated with HIV-positive patients with
      diarrhea in Western India. Stools of all HIV-positive patients with diarrhea
      should thoroughly be investigated to identify etiologic agents for proper
      management.

PMID- 24672181
TI  - Non-zoonotic Pasteurella multocida Infection as a Cause of Septic Shock in a
      Patient with Liver Cirrhosis: A Case Report and Review of the Literature.
AB  - Pasteurella multocida is a Gram-negative organism characterized morphologically
      as coccobacillus. It is the commonest organism infecting pet bites. However,
      severe infections may occur in the absence of animal bites or scratches.
      Pasteurella multocida serves as an opportunistic pathogen in humans, especially
      in patients with depressed immune system. Few cases in the literature identify
      Pasteurella multocida as the causative agent of septic shock, especially in
      cirrhotic patients. We report a patient who presented with septic shock as a
      result of Pasteurella multocida bacteremia, without prior history of animal
      exposure. 

PMID- 24672180
TI  - West nile virus and its theories, a big puzzle in Mexico and latin america.
AB  - It has been 13 years since the first outbreak of West Nile Virus (WNV) occurred
      in the Americas. Since then, thousands of human cases have been reported in the
      United States. In contrast, there has not yet been an outbreak of WNV in any
      Latin American countries, including Mexico where <20 cases have been reported. We
      aimed to review publications to gather the main theories related to the fact that
      not all the countries of the continent reported human cases or that they have
      reported few cases since the introduction of WNV in the Western Hemisphere. We
      identified relevant publications using the PubMed database. Furthermore, we
      present on-line published information from Mexico. We found that researchers have
      tried to explain this phenomenon using several theories, like pre-existing
      antibodies against a heterotypical virus that have conferred cross protection in
      the population. Another explanation is that the strains circulating in Latin
      America are attenuated or that they came from a different origin of introduction
      in the continent. Another theory is that a conclusive diagnostic in regions where
      more than one Flavivirus is circulating results in cross-reaction in serological
      tests. Probably the sum of factors described by researchers in these theories in
      order to explain the behavior of the virus has resulted in the low number of
      reported cases in Latin America. 

PMID- 24672182
TI  - Spontaneous pneumorrhachis and transverse myelitis complicating purulent
      meningitis.
AB  - Pneumorrhachis is the presence of air in the spinal canal; mostly, it has an
      iatrogenic origin. The association of this entity with spontaneous
      pneumomediastinum without any pneumothorax is rarely reported in the literature.
      The spontaneous resorption is the usual evolution. The association to acute
      transverse myelitis is discussed by the authors. The patient is a 21-year-old
      male with pneumorrhachis associated to a spontaneous pneumomediastinum was
      admitted at the emergency department for bacterial meningitis. The antibiotherapy
      has marked the clinical profile by disappearance of the meningeal signs in the 48
      h after admission. In contrast, the neurological symptoms were of marked
      aggravation by appearance of a tetraparesis with a respiratory distress syndrome
      having required artificial ventilation. The computed tomography (CT) scan showed
      a typical hypodensity corresponding to paramedullary air extending to several
      thoracic segments. The spinal magnetic resonance imaging (MRI) showed a high
      cervical medullary edema without signs of compression. The patient died within 15
      days with a profile of vasoparalysis resistant to vasoactive drugs.
      Pneumomediastinum associated to pneumorrhachis and transverse myelitis
      complicating purulent meningitis is a rare entity. Although the usual evolution
      is favorable, the occurrence of serious complications is possible. 

PMID- 24672183
TI  - Atypical Dengue Meningitis in Makkah, Saudi Arabia with Slow Resolving, Prominent
      Migraine like Headache, Phobia, and Arrhythmia.
AB  - Although dengue meningitis is a rare presentation of dengue infection, our aim is
      to focus on atypical presentation of dengue meningitis that may appear in dengue
      endemic area like the Makkah region. We report two cases of clinical meningitis
      with positive dengue virus (DENV) IgM in cerebrospinal fluid, followed for
      minimal 3 months for their prominent attacks of migraine like headache, phobia,
      and arrhythmia. With special consideration to attack time, type, severity, and
      respond to classical therapy, using regular ECG monitoring, visual analog pain
      score and neuropsychological assessments were done. Both cases showed resistant
      migraine like headaches to classic anti-migraine therapy except for strong NSAID
      and narcotics with tendency to have severe to extreme severe daily migraine like
      headache on early to late afternoon time, associated with non-fatal arrhythmias
      and extreme death phobia, that resolve slowly in a minimal 3 month period. In
      conclusion, dengue meningitis in the endemic area may present atypically. 

PMID- 24672184
TI  - Midlife disorders.

PMID- 24672185
TI  - The role of oxidative stress in menopause.
AB  - This review will discuss the concept of reproductive aging, which includes the
      definition of menopause, its symptoms, and predisposing conditions. It will
      elaborate upon the contributory factors implicated in the pathogenesis of
      menopause, focusing most prominently on oxidative stress. Specifically, this
      paper will explain how oxidative stress, in the form of free radicals and
      antioxidant deficiencies, has been directly linked to the decline of estrogen
      during reproductive aging. Additionally, this paper will elaborate upon the
      treatment options aimed at mitigating the menopausal symptoms and hormonal
      deficiencies that can lead to various disease processes. Treatment options such
      as hormonal therapy, antioxidant supplementation, and lifestyle modification have
      been explored for their effectiveness in treating and preventing the symptoms and
      sequelae of menopause. The majority of information in this review was obtained
      through PubMed and the National Library of Medicine. While most references in
      this paper are original research articles, a limited number of references are
      comprehensive reviews on the topic. 

PMID- 24672186
TI  - Emerging therapies for the treatment of osteoporosis.
AB  - Osteoporosis is a chronic disease of the osseous system characterized by
      decreased bone strength and increased fracture risk. It is due to an imbalance in
      the dynamic ongoing processes of bone formation and bone resorption. Currently
      available osteoporosis therapies like bisphosphonates, selective estrogen
      receptor modulators (SERMs), and denosumab are anti-resorptive agents.
      Parathyroid hormone analogs like teriparatide are the only anabolic agents
      currently approved for osteoporosis treatment. The side-effects and limited
      efficacy of the presently available therapies has encouraged extensive research
      into the pathophysiology of the disease and newer drug targets for its treatment.
      The novel anti-resorptive agents being developed are newer SERMs,
      osteoprotegerin, c-src (cellular-sarcoma) kinase inhibitors, alphaVbeta3 integrin
      antagonists, cathepsin K inhibitors, chloride channel inhibitors, and nitrates.
      Upcoming anabolic agents include calcilytics, antibodies against sclerostin and
      Dickkopf-1, statins, matrix extracellular phosphoglycoprotein fragments activin
      inhibitiors, and endo-cannabinoid agonists. Many of these new drugs are still in
      development. This article provides an insight into the emerging drugs for the
      treatment of osteoporosis. 

PMID- 24672187
TI  - Correlation between clinical presentation and urodynamic findings in women
      attending urogynecology clinic.
AB  - INTRODUCTION: Urodynamic studies objectively observe lower urinary tract function
      and dysfunction so that an appropriate treatment can be planned. In the present
      study, we tried to evaluate the role of urodynamic studies in the final diagnosis
      and management plan in patients attending an urogynecology clinic. MATERIALS AND
      METHODS: This observational study was conducted in an urogynecology clinic. 202
      women were included. After detailed history, pelvic examination and introital
      sonography these women were subjected to urodynamic study. During the filling
      cystometry detrusor activity, first desire to void and bladder capacity was
      recorded. This was followed by urethral pressure measurements, when functional
      urethral length, maximum urethral closure pressure and stress urethral pressure
      profile was recorded. RESULTS: Most prevalent complaint was mixed urinary
      incontinence (33.17%), followed by stress incontinence (31.68%) and urge
      incontinence (13.37%). According to the standard urodynamic definition 66.33%
      were normal in the population studied. None of the urodynamic parameters
      individually or in combination were found to be very useful for establishing a
      diagnosis. CONCLUSION: Establishment of the final diagnosis of urinary
      incontinence and planning of management should be based on detailed history,
      physical examination, bladder diaries, and careful interpretation of urodynamic
      data. Urodynamic study; however, doesn't seem to be imperative to establish a
      diagnosis in uncomplicated cases where symptoms and signs are reliable and
      correlating.

PMID- 24672188
TI  - Efficacy and tolerability of fixed dose combination of metoprolol and amlodipine
      in Indian patients with essential hypertension.
AB  - BACKGROUND: This open-labeled, post-marketing study was conducted to assess the
      efficacy and tolerability of fixed dose combination of amlodipine and metoprolol
      extended release capsules in mild to moderate hypertension in adult Indian
      patients. MATERIALS AND METHODS: Of 101 enrolled patients, 64 drug naive patients
      were treated with regimen A (amlodipine 5 mg + metoprolol 25 mg) and those with
      prior history of hypertension (n = 37) were treated with regimen B (amlodipine 5
      mg + metoprolol 50 mg) for 8 weeks. Treatment response was assessed at week 4 and
      8. Dose up titration to regimen B was carried out for those who failed to achieve
      the target blood pressure (BP) at week 4 in regimen A and additional
      antihypertensives were added to those in regimen B. Safety laboratory tests were
      performed at baseline and end of study. RESULTS: Mean age (+/-SD) of patients was
      53.36 (+/-11.26) years and body weight (+/-SD) 63.40 (10.03) kg. Ninety five
      patients (94.06%) were only hypertensive and 6 (5.94%) had hypertension with
      history of coronary artery disease; mean duration (+/-SD) of hypertension was
      42.50 (48.07) months. At baseline, patients had a mean (+/-SD) systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) of 154.98 (+/-7.76) mmHg and
      95.55 (+/-5.70) mmHg respectively. There was a statistically significant (P <
      0.001) reduction of 12.16% and 14.69% in SBP, 11.49% and 14.65% in DBP at week 4
      and week 8 respectively, compared to baseline. Normalization of overall BP was
      achieved in 49.49% and 70.71% patients at week 4 and 8, respectively. Peripheral
      edema was reported in 2.97% (3/101) patients. CONCLUSION: This combination was
      safe, efficacious, and well-tolerated in study population.

PMID- 24672189
TI  - Comparison of sexual dysfunction between diabetic and non-diabetic women.
AB  - CONTEXT: Sexual dysfunction (SD) among diabetic women is an important disorder.
      It has many negative effects on general health. AIMS: This study aimed to compare
      SD status between diabetic and non-diabetic women. SETTINGS AND DESIGN: This
      study was conducted on 200 women, half of them diabetic and the others as non
      diabetic in Tohid Hospital (Sanandaj, Iran). MATERIALS AND METHODS: The non
      diabetic group was matched for age (+/-5 years) and education. Data were
      collected using an interview-based questionnaire containing demographic
      characteristics and female sexual function index (FSFI). STATISTICAL ANALYSIS
      USED: Univariate and multivariate analyses were performed to assess and interpret
      the results. RESULTS: Analyses of the data showed that low educational levels,
      longer duration of diabetes and poor controlled diabetes were associated with the
      lower FSFI scores. In both groups the prevalence of SDs for all FSFI domains was
      high. Furthermore, multivariate analysis showed that these three variables were
      associated with lower FSFI scores. CONCLUSIONS: Study confirms that Kurdish
      Iranian diabetic women are at an increased risk of SD. Low educational level,
      longer duration of diabetes, and poor controlled diabetes were associated with a
      lower FSFI score.

PMID- 24672190
TI  - Study of addiction problems and morbidity among geriatric population in rural
      area of Aurangabad district.
AB  - RESEARCH QUESTION: What is the addiction problems and morbidity profile pattern
      of geriatric population in rural area? OBJECTIVES: i) To study the morbidity
      profile of elderly. ii) To study the addiction problems among elderly. MATERIALS
      AND METHODS: The present study was carried out at the field practice area of
      Rural Health and Training Center (RHTC), Paithan of Government Medical College,
      Aurangabad during the period of September 1, 2006 to August 31, 2007. Total
      elderly population according to the definition at the field practice area of
      RHTC, Paithan was 3128. Enlisting of the study subjects was done by systematic
      random sampling by using Loksabha electoral list of 2005. A sample of 20% of
      total elderly population was taken by including every fifth elderly from the
      electoral list. STUDY DESIGN: Cross-sectional study. SETTINGS: Field practice
      area of RHTC, Paithan of Government Medical College, Aurangabad. PARTICIPANTS:
      Elderly above 60 years of age. SAMPLE SIZE: 625 which was 20% of total elderly at
      RHTC, Paithan. STATISTICAL ANALYSIS: Chi-square test. RESULTS: a) The study found
      that the prevalence of addiction among males was 68.34%, the prevalence of
      various addictions were smoking 29.96%, alcohol 18.18%, tobacco chewing 29.29%
      and among females, 45.42% elderly females use to chew tobacco. b) Prevalence of
      cataract was 40.16%, joint pain - 23.04%, chronic obstructive pulmonary disorder
      (COPD) - 7.52%, senescent forgetfulness - 10.88%, hemorrhoids - 8.64%, benign
      enlargement of prostate (BEP) - 7.20% in elderly males, hearing impairment -
      24.8%, hypertension - 21.6%, diabetes mellitus - 13.92%, and anemia - 8.32%.

PMID- 24672191
TI  - Cross-cultural variation in symptom perception of hypoglycemia.
AB  - BACKGROUND: Cross-cultural differences in attitudes and practices related to
      diabetes are well-known. Similar differences in symptom reporting of endocrine
      conditions such as menopause are well documented. Minimal literature is available
      on the cross-cultural variation in reporting of hypoglycemic symptoms. AIMS: This
      cross-sectional study aimed to assess the symptoms of hypoglycemia encountered by
      diabetologists who deal with patients from different language groups from various
      states of North and West India and Nepal. MATERIALS AND METHODS: Eighty three
      doctors from six Indian states and Nepal, attending a continuing medical
      education program were requested to fill a detailed, pre-tested, Likert scale
      based questionnaire which assessed the frequency and symptoms with which patients
      presented with hypoglycemia in their clinical practice. Data were analyzed based
      on geographic location of the diabetologists and language spoken by their
      patients (Hindi vs. Gujarati). RESULTS: Gujarati-speaking patients tended to
      report to their doctors, a greater inability to work under pressure and a higher
      frequency of intense hunger during hypoglycemia. They were less likely to report
      specific adrenergic (inward trembling), neuroglycopenic (feeling down over
      nothing), and nocturnal (crumpled bedsheets upon waking up) symptoms. CONCLUSION:
      Significant cross-cultural differences related to the symptomatology of
      hypoglycemia are noted. Indian diabetologists should be aware of the varying
      presentation of hypoglycemia based on language and ethnic background.

PMID- 24672192
TI  - Study of menopausal symptoms, and perceptions about menopause among women at a
      rural community in Kerala.
AB  - BACKGROUND: Menopausal health demands priority in Indian scenario due to increase
      in life expectancy and growing population of menopausal women. Most are either
      unaware or do not pay adequate attention to these symptoms. AIMS: To find the
      prevalence of menopausal symptoms and perceptions regarding menopause among
      menopausal women of Kerala. SETTINGS AND DESIGN: A community based cross
      sectional house to house survey was conducted at Anjarakandy a field practice
      area under Kannur Medical College, Anjarakandy. MATERIALS AND METHODS: The study
      was conducted among 106 postmenopausal women staying more than 6 months at
      Anjarakandy with the help of pretested questionnaire administered by a trained
      social worker from January to October 2009. Before that a pilot study was
      conducted and required sample size of 100 was calculated. Random sampling of
      houses was done. STATISTICAL ANALYSIS: Data was coded, entered, and analyzed
      using SPSS 15. Chi-square test, proportions, and percentages were used. RESULTS:
      The mean age of attaining menopause was 48.26 years. Prevalence of symptoms among
      ladies were emotional problems (crying spells, depression, irritability) 90.7%,
      headache 72.9%, lethargy 65.4%, dysuria 58.9%, forgetfulness 57%, musculoskeletal
      problems (joint pain, muscle pain) 53.3%, sexual problems (decreased libido,
      dyspareunia) 31.8%, genital problems (itching, vaginal dryness) 9.3%, and changes
      in voice 8.4%. Only 22.4% of women knew the correct cause of menopause.
      CONCLUSIONS: Thus study stated that all the ladies were suffering from one or
      more number of menopausal symptoms. Ladies should be made aware of these
      symptoms, their causes and treatment respectively.

PMID- 24672193
TI  - Lacunar infarction with oral contraceptives: An unusual case report.
AB  - Combined oral contraceptives are one of the risk factor for stroke in women. We
      report a case of an arterial ischemic stroke due to lacunar infarction in a 35
      year-old previously healthy female patient induced after 3 years on Sukhi an oral
      contraceptive after two times artificial abortions. A brain MRI finding was
      suggestive of lacunar infarction. Her symptoms improved after stopping the oral
      contraceptive and putting her on I.V heparin therapy. 

PMID- 24672194
TI  - Conservative treatment of a femoral neck fracture following nail removal.
AB  - With increased longevity, the management of fragility fractures in the elderly is
      becoming more frequent. In particular, hip fractures have considerable importance
      due to the significant morbidity and mortality. A 67-year-old woman underwent
      intramedullary nail (IMN) removal inserted for a pertrochanteric fracture that
      had occurred 20 months earlier. This was indicated due to continuous discomfort
      related to the protruding apex of the implant over the great trochanter. Due to
      pain persistence two days after surgery, a computed tomography (CT) scan was
      performed, documenting a minimally displaced impacted subcapital femoral neck
      fracture. Conservative management with close radiographic follow-up was
      conducted. After six months, the patient had returned to previous daily
      activities and a satisfactory range of motion was achieved without pain on
      walking. The purpose of our paper is to discuss the decision of removing hardware
      in the elderly osteoporotic patient and to analyze the possibility to
      conservatively treat an impacted minimally displaced subcapital fracture
      occurring after the removal of an IMN inserted previously for the treatment of a
      trochanteric fracture. In the elderly population with decreased bone quality, the
      removal of intramedullary implants of the proximal femur should be carefully
      evaluated, and osteoporotic patients undergoing reduction and fixation of femoral
      fractures should be encouraged to start antiosteoporotic therapy (bisphosphonate,
      teriparatide) to reduce the risk of further bone loss. Conservative treatment
      should be considered for the management of lesser symptomatic minimally displaced
      impacted fractures, where the inherent stability of the fracture allows rapid
      healing without further surgical attempts. 

PMID- 24672195
TI  - Endometrial cartilaginous metaplasia: A case report with literature review.
AB  - Endometrial metaplasias are of two types, epithelial metaplasia which is commonly
      encountered and stromal metaplasia, unusually seen. This includes formation
      within endometrial stroma, islands of smooth muscle, cartilage, and bone.
      Endometrial stromal (cartilaginous) metaplasias are conditions frequently
      overlooked and misdiagnosed. Hence, a careful clinical and histopathological
      examination is required to avoid the misinterpretation of non-tumor cartilaginous
      foci as a component of malignant neoplasm. Herein, we report a rare case of
      endometrial cartilaginous metaplasia which was an incidental finding in a 38-year
      old female with third degree uterovaginal prolapse. 

PMID- 24672196
TI  - Qualitative research in midlife health.

PMID- 24672197
TI  - Obesity, sarcopenia and postmenopausal osteoporosis: An interlinked triad!

PMID- 24672198
TI  - Lifestyle and dietary factors determine age at natural menopause.
AB  - A literature search was done using PubMed. The age at natural menopause (ANM)
      depends on various factors like genetic, environmental, socioeconomic,
      reproductive, dietary, and lifestyle of which some like nulliparity, vegetarian
      diet, smoking, high fat intake, cholesterol, and caffeine accelerates; while
      others like parity, prior use of oral contraceptive pills, and Japanese ethnicity
      delays the ANM. ANM is an important risk factor for long-term morbidity and
      mortality; and hence, the need to identify the modifiable risk factors like diet
      and lifestyle changes. Delayed menopause is associated with increased risk of
      endometrial and breast cancer, while early ANM enhances the risk for
      cardiovascular diseases and osteoporosis. The correlation between diet and ANM
      has not been extensively studied; however, whatever studies have been done till
      now point towards role of high intake of total calories, fruits, and proteins in
      delaying the ANM, while high polyunsaturated fat intake accelerates it. The role
      of dietary soy, total fat, saturated fat, red meat, and dietary fiber in
      determining the ANM has been controversial and needs further studies to
      substantiate it. The lifestyle factors like current smoking and vigorous exercise
      have been significantly associated with early menopause, while moderate alcohol
      consumption delays the ANM. Large prospective studies are needed to study the
      association of ANM and other modifiable factors like passive smoking fish
      consumption, soy, and various types of tea. The knowledge of modifiable
      determinants of ANM can help in setting up menopausal clinics and initiating
      health programs specially in developing countries. 

PMID- 24672199
TI  - Obesity: Friend or foe for osteoporosis.
AB  - Osteoporosis and obesity are worldwide health problems. Interestingly, both are
      associated with significant morbidity and mortality. Both the diseases have
      common linkage as bone marrow mesenchymal stromal cells are the common precursors
      for both osteoblasts and adipocytes. Aging may shift composition of bone marrow
      by increasing adipocytes, osteoclast activity, and decreasing osteoblast
      activity, resulting into osteoporosis. Adipocytes secret leptin, adiponectin,
      adipsin, as well as proinflammatory cytokines, that contributes in pathogenesis
      of osteoporosis. This new concept supports the hypothesis, that the positive
      correlation of weight and body mass index (BMI) with bone mineral density (BMD)
      is not confirmed by large population-based studies. Thus, the previous concept,
      that obesity is protective for osteoporosis may not stand same as bone marrow fat
      deposition (adipogenesis) seen in obesity, is detrimental for bone health. 

PMID- 24672200
TI  - Prognosis of vulval cancer with lymph node status and size of primary lesion: A
      survival study.
AB  - INTRODUCTION: Squamous cell cancer of the vulva is a rare disease with an annual
      incidence of two to three per 100,000 women. Lymph node metastasis is the most
      important prognostic factor for the recurrence and survival in vulval carcinoma.
      MATERIALS AND METHODS: It is a retrospective study of 18 cases, operated in our
      institute from 2006 to 2009 and followed up till July, 2012. These patients were
      divided into two group of node positive and node negative and compared for
      recurrence and survival. RESULT: Ten patients had lymph node metastasis and eight
      had no lymph node metastasis. Recurrence rate was 40% and 12.5% in node positive
      and negative groups, respectively. Adjuvant radiation when given to node negative
      bulky tumor showed no recurrence compared to one out of two in the non-irradiated
      group. Survival was only 25% in node positive recurrent cases. CONCLUSION: Lymph
      node positivity added a great risk for future recurrence. Prophylactic radiation
      in node negative, bulky tumor is helpful.

PMID- 24672201
TI  - Polymerase chain reaction and deoxyribonucleic acid-sequencing based study on
      distribution of human papillomavirus 16/18 among histopathological types of
      cervical intra-epithelial neoplasia and primary invasive cervical carcinoma: A
      scenario in North Bengal, India.
AB  - INTRODUCTION: Human papillomavirus (HPV) types 16/18 are reportedly most common
      in cervical cancer (CaCx) with geographical variation of genotypes. HPV16
      predominates both in squamous cell carcinoma (SCC) and adenocarcinoma in India,
      contrary to reported global predominance of HPV18 in the latter. Our study was
      aimed to determine the occurrence of HPV16/18 among histopathological types of
      cervical intra-epithelial neoplasia (CIN) and invasive CaCx from North Bengal,
      India and to identify any major deviation from the known Indian scenario of
      distribution of HPV16/18 genotypes in cases of SCC and adenocarcinoma. MATERIALS
      AND METHODS: This was a retrospective, cross-sectional, case-only type of study,
      in which 40 cases were histopathologically diagnosed as CIN/CaCx, on which
      polymerase chain reaction (PCR), deoxyribonucleic acid (DNA)-sequencing and
      bioinformatics by basic search local alignment tool were performed for HPV
      genotyping. STATISTICAL ANALYSIS: The distribution of HPV genotypes among cases
      of SCC and adenocarcinoma was compared by Fisher's exact-test. RESULTS: HPV was
      detected in 97.5% (39/40) cases. HPV16-infected cases (32/39; 82.05%)
      predominated over HPV18-infected ones (7/39; 17.95%). However, HPV18-only
      infection was significantly (P = 0.0045, one-sided Fisher's exact test) more
      among adenocarcinoma (3/4; 75%) than SCC (2/26; 7.69%) contrary to HPV16-only
      infection (SCC = 24/26, 92.31%; adenocarcinoma = 1/4; 25%) whereas both CIN3
      cases were HPV16-positive. CONCLUSION: Predominance of HPV18 over HPV16 in cases
      of adenocarcinoma in this region was contrasting to that of earlier Indian
      studies suggesting research on HPV18 related cervical carcinogenesis. PCR and DNA
      sequencing could prove to be highly effective tools in HPV detection and
      genotyping. The study reported HPV16/18 infection in almost 98% of the cases, the
      knowledge about which might prove useful in future population based studies on
      HPV genotyping and designing of appropriate HPV-vaccines for this region.

PMID- 24672202
TI  - Effect of life-style modification on postmenopausal overweight and obese Indian
      women: A randomized controlled 24 weeks preliminary study.
AB  - AIM: The aim of the following study is to evaluate the effect of life-style
      modification on postmenopausal (PM) overweight and obese Indian women in a
      randomized controlled 24 week study. MATERIALS AND METHODS: Two groups were
      formed Group I (n = 30) was designated as intervention (dietary and exercise
      group) and Group II (n = 24) served as control. Comparison of weight, waist
      circumference (WC) and body mass index (BMI) were made and compared among two
      groups at 4, 8, 16 and 24 weeks. RESULTS: Mean age at menopause was 48.35 years
      versus 49.65 years; mean number of menopausal symptoms were 5.70 +/- 1.76 versus
      5.10 +/- 1.56 and mean duration since menopause was 2.70 versus 2.90 years in
      Groups I and II respectively. When the effect of Group I and control on weight
      was compared at 4, 8, 16 and 24 weeks, there was no significant difference
      between them up to 8 week. At 8 weeks Group I caused a significant decrease in
      weight (P <= 0.05) when compared with control arm and which continued throughout
      the study period (P < 0.05) at both 16 and 24 weeks. Group I produced a
      significant reduction in WC from 8 weeks onwards up to 24 weeks (P <= 0.05). BMI
      was statistically significant in Group I and the effect started at 4(th) week (P
      <= 0.05) and the differences in BMI reduction were highly significant at 16(th)
      and 24(th) weeks (P <= 0.001). CONCLUSION: The results of the present study
      strongly recommend the life-style management to be incorporated in daily style of
      postmenopausal women under controlled supervision.

PMID- 24672203
TI  - First Indian prospective randomized comparative study evaluating adherence and
      compliance of postmenopausal osteoporotic patients for daily alendronate, weekly
      risedronate and monthly ibandronate regimens of bisphosphonates.
AB  - AIM: The aim of the following study is to evaluate adherence and compliance of
      postmenopausal osteoporotic patients for different regimens of bisphosphonates
      (BP). MATERIALS AND METHODS: A prospective observational randomized comparative 1
      year study was undertaken to evaluate the adherence/compliance rates of most
      commonly prescribed daily alendronate (ALN), weekly risedronate (RIS) and monthly
      ibandronate (IBN) BP regimens. RESULTS: Nearly 40% was the 1 year adherence rate
      with BP and 41.33% of non-compliance. Whereas, 8.66% was interrupted compliance
      rate and 6% switched over to other anti-osteoporotic treatment. The three
      treatment arm did not vary significantly. However, numerically maximum adherence
      rate of 56% was recorded in monthly BP regimen followed by weekly (36%) and daily
      regimen (32%). Medication possession rate confirmed on a follow-up visit was
      maximum with monthly regimen as 84.61% followed by daily (62.5%) and weekly
      (61.11%) respectively. Average time in days for non-adherence was 48, 56 and 92
      day with daily ALN, weekly RIS and monthly IBN regimen respectively. Age, mean
      age at menopause, demographical profile failed to influence the adherence.
      Concomitant treatment for co-morbid condition (57.14%), unawareness about
      osteoporosis (OP) (50%), cost of treatment (45.33%), belief that drugs is for
      their general disability (39.28%), physician's failure to stress the need and
      necessary calcium + vitamin D daily requirement (23.80%) each were the most
      prevalent factors responsible for non-adherence. Intolerance and adverse drug
      reactions were responsible for only 13.09% and 11.90% of non-adherence.
      CONCLUSION: Treatment compliance is poor with daily ALN, weekly RIS and monthly
      IBN regimen along with calcium and vitamin D3 in Indian paramedical workers
      suffering OP.

PMID- 24672204
TI  - Vaginal pH: A marker for menopause.
AB  - INTRODUCTION: Menopause is suspected with age, cessation of menstruation for more
      than a year and presence of symptoms. The diagnosis of menopause is confirmed by
      follicle stimulating hormone (FSH) levels >40 IU/L. Few studies have focused on
      vaginal pH for menopausal diagnosis. It is a simple, non-invasive and inexpensive
      method for this purpose. AIM OF THE STUDY: The following study is to correlate
      the serum follicle stimulating hormone (FSH) level with vaginal pH estimation in
      menopause. MATERIALS AND METHODS: This is a cross-sectional descriptive study
      conducted in 173 women aged 31-60 years with menopausal symptoms who attended the
      Menopausal Clinic of our hospital from January 2012 to January 2013. Vaginal pH
      was measured using pH micro-meter strips and serum FSH levels were measured using
      immunoassay methods. The data obtained was then analyzed using Statistical
      Package for the Social Sciences software (version 17) and results were evaluated
      statistically by the Chi-square and Kappa tests. P <= 0.05 was considered to be
      statistically significant. RESULTS: According to our study of the 173 women
      studied, mean FSH level was 46.5 IU/L and mean vaginal pH was 5.3. If the
      menopausal hallmark is considered to be vaginal pH >4.5 and serum FSH >=40 IU/L,
      the sensitivity of vaginal pH for menopausal diagnosis was 84.9% and of serum FSH
      is 77.4%, respectively. CONCLUSION: Vaginal pH is a simple, accurate and cost
      effective tool that can be suggested as a suitable and better alternative to
      serum FSH estimation for the diagnosis of menopause.

PMID- 24672205
TI  - Alzheimer disease in post-menopausal women: Intervene in the critical window
      period.
AB  - Alzheimer disease (AD) is a crippling neurodegenerative disorder. It is more
      common in females after menopause. Estrogen probably has a protective role in
      cognitive decline. Large amount of research has been carried out to see the
      benefits of hormone replacement therapy with regards to Alzheimer still its
      neuroprotective effect is not established. Recent studies suggest a reduced risk
      of AD and improved cognitive functioning of post-menopausal women who used 17
      beta-estradiol in the critical period. Use of 17 beta-estradiol in young and
      healthy post-menopausal women yields the maximum benefit when the neurons are
      intact or neuronal stress has just started. Hence intervention in the critical
      period is key in the prevention or delay of AD in post-menopausal women. 

PMID- 24672206
TI  - Sarcomatoid carcinoma of the cervix with foci of malignant melanoma.
AB  - INTRODUCTION: Sarcomatoid squamous cell carcinoma (SSCC) is a rare malignancy of
      the cervix. Until date around eighteen cases of SSCC have been reported in the
      literature. It is an aggressive tumor with poor prognosis. The tumor usually
      presents at an advanced stage. Similarly, primary melanomas of the uterine cervix
      are rare tumors with not more than 60 cases reported in the world literature. It
      also has a poor prognosis. There is no reported case of sarcomatoid carcinoma
      with malignant melanoma. Here, we are presenting a rare case of cervical
      carcinoma with histopathology suggestive of SSCC with foci of malignant melanoma
      proven by immunohistochemistry study. CASE REPORT: The present case report is
      about a 42-year-old, Mrs. SR, P5 L3 D1 A1 , presented with the complaints of
      intermittent bleeding per vaginum since last 3 years and severe pain in the right
      lower limb since 1 month. On examination, there was a proliferative growth in the
      cervix. Her magnetic resonance imaging (MRI) showed cervical mass lesion with
      right parametrial extension invading the right ureter and bladder wall causing
      hydroureteronephrosis with contiguous bilateral pelvic nodes. There were multiple
      lesions in the left femur. Diagnosis of carcinoma of cervix International
      Federation of Gynecology and Obstetrics stage IIIB with distant metastasis was
      made. Histopathology report was suggestive of sarcomatoid carcinoma with foci of
      melanocytic melanoma. She was planned to be treated with palliative radiation.
      DISCUSSION: About 90% of cervical carcinomas are squamous cell carcinoma.
      Adenocarcinoma constitute about 3-4% of all cervical carcinomas. Other rare
      pathologies are lymphoma, melanoma, sarcoma and metastatic tumors. Our case is a
      rare combination of sarcomatoid carcinoma with foci of malignant melanoma of
      cervix.

PMID- 24672207
TI  - Bladder neck leiomyoma presenting with acute retention of urine in an elderly
      female.
AB  - Acute painful retention of urine in a female is uncommon presentations. Bladder
      neck tumor presenting as acute painful retentions is rare clinical scenario. We
      present a case of the urinary bladder neck leiomyoma in a 45-year-old peri
      menopausal female who presented with acute painful retention of urine without
      prior history of lower urinary tract symptoms. Patient was managed with
      cystoscopy and transurethral endoscopic resection of the tumor. 

PMID- 24672208
TI  - Commentary on following of Menopausal Guidelines by practitioners in Indian
      setting.

PMID- 24672209
TI  - Guidelines for standard order sets.
AB  - Following the guidelines for standard order sets minimizes incorrect prescribing.

PMID- 24672210
TI  - Pharmacists, Deluged With Requirements, Pressure FDA to Standardize REMS
      Programs.
AB  - Pharmacists want the FDA to standardize REMS programs. 

PMID- 24672212
TI  - Pharmaceutical approval update.
AB  - Obinutuzumab (Gazyva) for chronic lymphocytic leukemia; ibrutinib (Imbruvica) for
      mantle-cell lymphoma; and sofosbuvir (Sovaldi) for chronic hepatitis C infection.

PMID- 24672213
TI  - Ingenol mebutate gel (picato): a novel agent for the treatment of actinic
      keratoses.
AB  - Ingenol mebutate gel (Picato) for actinic keratoses. 

PMID- 24672215
TI  - New congressional bill attempts to aid pharmacy response to drug shortages:
      compounding and tracing provisions seek to improve quality of drug supply.
AB  - The Drug Quality and Security Act is intended to prevent the sale of contaminated
      compounded agents, but the way in which facilities will be regulated is still
      unclear. Many safeguards will need to be implemented. 

PMID- 24672214
TI  - Olmesartan and drug-induced enteropathy.
AB  - In three case histories, patients' sprue-like symptoms improved when olmesartan
      (Benicar) therapy was withheld. 

PMID- 24672216
TI  - New oral anticoagulants for atrial fibrillation: are they worth the risk?
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in the U.S.
      Anticoagulation is recommended for stroke prevention in AF patients with
      intermediate-to-high stroke risk (i.e., patients with a CHADS2 score of 1 or
      greater). Warfarin was previously the only option for oral anticoagulation in
      these patients, but three new oral anticoagulants have become available as
      alternatives for warfarin in patients with nonvalvular AF. The advantages of the
      newer agents include a rapid onset, predictable pharmacokinetics, and no need for
      routine anticoagulation monitoring. Dabigatran (Pradaxa) and apixaban (Eliquis)
      have demonstrated improved efficacy compared with warfarin. Rivaroxaban (Xarelto)
      was non-inferior to warfarin for stroke prevention in AF. Apixaban demonstrated a
      reduced incidence of major bleeding compared with warfarin and a reduction in all
      cause mortality. Limitations to the use of the new oral anticoagulants include
      the lack of a reversal agent; an inability to use the therapies in specific
      patient populations (such as those with severe renal or hepatic impairment);
      limited experience with drug-drug and drug-disease interactions; and a lack of
      available coagulation tests to quantify their effects. Although the newer agents
      have higher acquisition costs, the benefits of cost savings may be derived from
      the potential for decreasing the incidence of hemorrhagic stroke and intracranial
      bleeding and reducing the need for anticoagulation monitoring. Benefits and risks
      should be carefully weighed before these agents are prescribed for patients
      presenting with new-onset AF. 

PMID- 24672217
TI  - American heart association scientific sessions 2013: agents for hypertension,
      heart failure, and acute myocardial infarction.
AB  - Topics include medications used in hypertension, heart failure, renal
      dysfunction, and myocardial infarction. 

PMID- 24672218
TI  - Clinical and genetic studies in a family with a new splice-site mutation in the
      choroideremia gene.
AB  - PURPOSE: To describe the clinical and molecular findings of an Italian family
      with a new mutation in the choroideremia (CHM) gene. METHODS: We performed a
      comprehensive ophthalmologic examination, fundus photography, macular optical
      coherence tomography, perimetry, electroretinography, and fluorescein angiography
      in an Italian family. The clinical diagnosis was supported by western blot
      analysis of lymphoblastoid cell lines from patients with CHM and carriers, using
      a monoclonal antibody against the 415 C-terminal amino acids of Rab escort
      protein-1 (REP-1). Sequencing of the CHM gene was undertaken on genomic DNA from
      affected men and carriers; the RNA transcript was analyzed with reverse
      transcriptase-PCR. RESULTS: The affected men showed a variability in the rate of
      visual change and in the degree of clinical and functional ophthalmologic
      involvement, mainly age-related, while the women displayed aspecific areas of
      chorioretinal degeneration. Western blot did not show a detectable amount of
      normal REP-1 protein in affected men who were hemizygous for a novel mutation,
      c.819+2T>A at the donor splicing site of intron 6 of the CHM gene; the mutation
      was confirmed in heterozygosity in the carriers. CONCLUSIONS: Western blot of the
      REP-1 protein confirmed the clinical diagnosis, and molecular analysis showed the
      new in-frame mutation, c.819+2T>A, leading to loss of function of the REP-1
      protein. These results emphasize the value of a diagnostic approach that
      correlates genetic and ophthalmologic data for identifying carriers in families
      with CHM. An early diagnosis might be crucial for genetic counseling of this type
      of progressive and still untreatable disease.

PMID- 24672219
TI  - Pan-American mDNA haplogroups in Chilean patients with Leber's hereditary optic
      neuropathy.
AB  - PURPOSE: The clinical impact of mDNA mutations on the development of Leber
      hereditary optic neuropathy (LHON) may be modulated by mitochondrial haplogroups,
      which vary across populations. The aim of this research was to determine the
      clinical spectrum and molecular characteristics, including the haplogroup, of 15
      South American families with LHON. METHODS: This study was a prospective,
      observational study conducted between March 2006 and August 2012. All patients
      were referred to the Clinical Hospital of the University of Chile, where the
      clinical study was conducted. Molecular studies were conducted at the Biomedical
      Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were
      identified with molecular analysis after initial neuroophthalmic examination at
      different centers throughout Chile. Clinical features of patients with LHON and
      maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy
      carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or
      m.14484T>C) were determined with restriction fragment length polymorphism
      analysis in all individuals. Mitochondrial haplogroups were determined with
      direct sequencing of two hypervariable regions (HV1 and HV2) and compared with
      reference sequences. RESULTS: The m.11778G>A mutation was found in 59 subjects
      (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the
      m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of
      symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21
      (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had
      Amerindian haplogroups: One family had the A2 haplogroup, four families had the
      B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g
      haplogroup. CONCLUSIONS: In this limited sample size, the Amerindian haplogroup
      A2 was associated with delayed onset of disease in this population. Patients with
      haplogroup C retained better vision than the patients with other haplogroups in
      this population. Disease in subjects with haplogroup D appeared to be
      underrepresented compared to the population at large.

PMID- 24672220
TI  - Polymorphism in the 11q24.1 genomic region is associated with myopia: a
      comprehensive genetic study in Chinese and Japanese populations.
AB  - PURPOSE: To evaluate the association of polymorphisms in the 11q24.1 genomic
      region and the CTNND2 gene with myopia. METHODS: We conducted a comprehensive
      meta-analysis included 6,954 cases and 9,346 controls. Odds ratios (ORs) were
      calculated using Carlin's method. Publication bias was assessed using Egger et
      al.'s approach. Sensitivity, heterogeneity, and trim and fill analyses were also
      conducted. RESULTS: For the 11q24.1 genomic region, the rs11218544 polymorphism
      showed significant association with myopia [OR and 95% confidence interval (CI):
      1.167 (1.032-1.319), p=0.013], while rs577948 showed no association with the
      disease [OR and 95%CI: 0.988 (0.727-1.342), p=0.936]. For the CTNND2 gene,
      neither rs6885224 nor rs12716080 was significantly associated with myopia
      {rs6885224: [OR and 95%CI: 1.051 (0.795-1.391), p=0.725], rs12716080: [OR and
      95%CI: 1.173 (0.990-1.390), p=0.065]}. CONCLUSIONS: Our study indicated that the
      11q24.1 genomic region, and particularly the rs11218544 polymorphism, has a
      genetic association with the development of myopia.

PMID- 24672221
TI  - Spectral-domain optical coherence tomography imaging of macula-off rhegmatogenous
      retinal detachment.
AB  - The timing of repair and the utility of spectral-domain optical coherence
      tomography (SD-OCT) for macula-off retinal detachment remains a controversial
      issue. Four patients who presented with macula-off retinal detachment underwent
      repair at various time points after symptom onset. Postoperative SD-OCT of the
      macula demonstrated correlation with final visual acuity. 

PMID- 24672222
TI  - Oculogyric crisis in a patient taking metoclopramide.
AB  - Oculogyric crisis is an acute dystonic reaction of the ocular muscles
      characterized by bilateral dystonic elevation of visual gaze lasting from seconds
      to hours. This reaction is most commonly explained as an adverse reaction to
      drugs such as antiemetics, antipsychotics, antidepressants, antiepileptics, and
      antimalarials. Although the incidence of metoclopramide-induced acute dystonic
      reactions has been reported as 25% in children, there have been few published
      cases on oculogyric crisis in general. It is important to be able to recognize
      this ocular side effect because, without a thorough patient history, symptoms can
      be confused with other diseases such as versive seizures, paroxysmal tonic upward
      gaze, and encephalopathy. In this paper, we report a case of oculogyric crisis
      induced by metoclopramide. 

PMID- 24672223
TI  - Diagnosis and management of neurotrophic keratitis.
AB  - Neurotrophic keratitis (NK) is a degenerative disease characterized by corneal
      sensitivity reduction, spontaneous epithelium breakdown, and impairment of
      corneal healing. Several causes of NK, including herpetic keratitis, diabetes,
      and ophthalmic and neurosurgical procedures, share the common mechanism of
      trigeminal damage. Diagnosis of NK requires accurate investigation of clinical
      ocular and systemic history, complete eye examination, and assessment of corneal
      sensitivity. All diagnostic procedures to achieve correct diagnosis and
      classification of NK, including additional examinations such as in vivo confocal
      microscopy, are reviewed. NK can be classified according to severity of corneal
      damage, ie, epithelial alterations (stage 1), persistent epithelial defect (stage
      2), and corneal ulcer (stage 3). Management of NK should be based on clinical
      severity, and aimed at promoting corneal healing and preventing progression of
      the disease to stromal melting and perforation. Concomitant ocular diseases, such
      as exposure keratitis, dry eye, and limbal stem cell deficiency, negatively
      influence the outcome of NK and should be treated. Currently, no specific medical
      treatment exists, and surgical approaches, such as amniotic membrane
      transplantation and conjunctival flap, are effective in preserving eye integrity,
      without ameliorating corneal sensitivity or visual function. This review
      describes experimental and clinical reports showing several novel and potential
      therapies for NK, including growth factors and metalloprotease inhibitors, as
      well as three ongoing Phase II clinical trials. 

PMID- 24672225
TI  - Biologics: the role of delivery systems in improved therapy.

PMID- 24672224
TI  - Diagnosis of dry eye disease and emerging technologies.
AB  - Dry eye is one of the most commonly encountered problems in ophthalmology. Signs
      can include punctate epithelial erosions, hyperemia, low tear lakes, rapid tear
      break-up time, and meibomian gland disease. Current methods of diagnosis include
      a slit-lamp examination with and without different stains, including fluorescein,
      rose bengal, and lissamine green. Other methods are the Schirmer test, tear
      function index, tear break-up time, and functional visual acuity. Emerging
      technologies include meniscometry, optical coherence tomography, tear film
      stability analysis, interferometry, tear osmolarity, the tear film normalization
      test, ocular surface thermography, and tear biomarkers. Patient-specific
      considerations involve relevant history of autoimmune disease, refractive surgery
      or use of oral medications, and allergies or rosacea. Other patient
      considerations include clinical examination for lid margin disease and presence
      of lagophthalmos or blink abnormalities. Given a complex presentation and a
      variety of signs and symptoms, it would be beneficial if there was an
      inexpensive, readily available, and reproducible diagnostic test for dry eye. 

PMID- 24672227
TI  - Safety, efficacy, and patient acceptability of rifaximin for hepatic
      encephalopathy.
AB  - Hepatic encephalopathy is a complex disease entity ranging from mild cognitive
      dysfunction to deep coma. Traditionally, treatment has focused on a reduction of
      ammonia through a reduced production, absorption, or clearance. Rifaximin is a
      nonabsorbable antibiotic, which reduces the production of ammonia by gut bacteria
      and, to some extent, other toxic derivatives from the gut. Clinical trials show
      that these effects improve episodes of hepatic encephalopathy. A large randomized
      trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy.
      Most patients were treated concurrently with lactulose. Trials have varied
      greatly in design, outcomes, and duration of treatment regimes. Although a number
      of retrospective studies have indicated that long-term treatment with rifaximin
      is safe and possibly beneficial, high quality trials are needed to further
      clarify efficacy and safety of long-term treatment with rifaximin and evaluate
      effects of combination therapy with lactulose and branched-chain amino acids for
      patients with liver cirrhosis and hepatic encephalopathy. 

PMID- 24672228
TI  - Factors that lessen the burden of treatment in complex patients with chronic
      conditions: a qualitative study.
AB  - PURPOSE: Patients with multiple chronic conditions (multimorbidity) often require
      ongoing treatment and complex self-care. This workload and its impact on patient
      functioning and well-being are, together, known as treatment burden. This study
      reports on factors that patients with multimorbidity draw on to lessen
      perceptions of treatment burden. PATIENTS AND METHODS: Interviews (n=50) and
      focus groups (n=4 groups, five to eight participants per group) were conducted
      with patients receiving care in a large academic medical center or an urban
      safety-net hospital. Interview data were analyzed using qualitative framework
      analysis methods, and themes and subthemes were used to identify factors that
      mitigate burden. Focus groups were held to confirm these findings and clarify any
      new issues. This study was part of a larger program to develop a patient-reported
      measure of treatment burden. RESULTS: Five major themes emerged from the
      interview data. These included: 1) problem-focused strategies, like routinizing
      self-care, enlisting support of others, planning for the future, and using
      technology; 2) emotion-focused coping strategies, like maintaining a positive
      attitude, focusing on other life priorities, and spirituality/faith; 3)
      questioning the notion of treatment burden as a function of adapting to self-care
      and comparing oneself to others; 4) social support (informational, tangible, and
      emotional assistance); and 5) positive aspects of health care, like coordination
      of care and beneficial relationships with providers. Additional subthemes arising
      from focus groups included preserving autonomy/independence and being proactive
      with providers. CONCLUSION: Patients attempt to lessen the experience of
      treatment burden using a variety of personal, social, and health care resources.
      Assessing these factors in tandem with patient perceptions of treatment burden
      can provide a more complete picture of how patients fit complex self-care into
      their daily lives.

PMID- 24672229
TI  - Orthodontic treatment need for adolescents in the Campania region: the
      malocclusion impact on self-concept.
AB  - BACKGROUND: Dental malocclusions can be considered not only as an oral health
      problem, because they are linked to quality of life perception. Many factors
      related to malocclusion have strong influences on the perception of facial
      esthetics (eg, anterior tooth alignment, tooth shape and position, lip thickness,
      symmetric gingival or tooth contour, lip profile, and overjet). Many reports have
      shown that the perception of facial esthetics can influence psychological
      development from early childhood to adulthood. The aim of this study is to
      investigate the effect of dental malocclusion on self-esteem in a sample of
      adolescents. MATERIALS AND METHODS: The study population was composed of 516
      orthodontically untreated subjects (256 males) mean ages 13.75+/-1.977 years
      recruited from schools in the Campania region of Italy between January 2011 and
      July 2011. To evaluate the self-esteem grade in our population, all subjects
      filled out the Multidimensional Self Concept Scale questionnaire and attended an
      orthodontic clinical evaluation to estimate dental occlusal aspects. RESULTS:
      Pearson's analysis shows the relationship in our sample between some occlusal
      characteristics (crossbite and dental crowding) and aspects of self-concept
      evaluation (social, competence, academic, physical, and global score) of the
      Multidimensional Self Concept Scale questionnaire. Moreover, logistic regression
      analysis shows the potential role of dental crowding (odds ratio 5.359; 95%
      confidence interval 3.492-8.225) and crossbite (odds ratio 6.153; 95% confidence
      interval 3.545-10.678) as risk factors for development of global self-concept
      score abnormalities. CONCLUSION: Our findings confirm the relationship between
      psychosocial well-being, self-esteem, and dental malocclusion among adolescents.

PMID- 24672230
TI  - Frailty syndrome: an overview.
AB  - Frailty is a common and important geriatric syndrome characterized by age
      associated declines in physiologic reserve and function across multiorgan
      systems, leading to increased vulnerability for adverse health outcomes. Two
      major frailty models have been described in the literature. The frailty phenotype
      defines frailty as a distinct clinical syndrome meeting three or more of five
      phenotypic criteria: weakness, slowness, low level of physical activity, self
      reported exhaustion, and unintentional weight loss. The frailty index defines
      frailty as cumulative deficits identified in a comprehensive geriatric
      assessment. Significant progress has recently been made in understanding the
      pathogenesis of frailty. Chronic inflammation is likely a key pathophysiologic
      process that contributes to the frailty syndrome directly and indirectly through
      other intermediate physiologic systems, such as the musculoskeletal, endocrine,
      and hematologic systems. The complex multifactorial etiologies of frailty also
      include obesity and specific diseases. Major clinical applications include risk
      assessment and stratification. This can be applied to the elderly population in
      the community and in a variety of care settings. Frailty may also be useful for
      risk assessment in surgical patients and those with cardiovascular diseases,
      cancer, or human immunodeficiency virus infection, as well as for assessment of
      vaccine effectiveness in older adults. Currently, exercise and comprehensive
      geriatric interdisciplinary assessment and treatment are key interventions for
      frailty. As understanding of the biologic basis and complexity of frailty further
      improves, more effective and targeted interventional strategies and innovative
      geriatric-care models will likely be developed. 

PMID- 24672231
TI  - Managing blood pressure control in Asian patients: safety and efficacy of
      losartan.
AB  - Hypertension is common in Asian populations and is a major cause of
      cardiovascular diseases. The prevalence of hypertension is increasing in many
      Asian countries. The overall prevalence of hypertension in India and the People's
      Republic of China has been estimated to be 20.6% in men and 22.6% in women.
      However, the rates of detection, treatment, and control of hypertension remain
      low in Asia. This reflects a low level of literacy and education, as well as a
      low level of access to medical care. To overcome these obstacles, strategies
      targeted at education, promotion, and optimization of medical care, are crucial
      to achieve target blood pressure control. Angiotensin receptor blockers are one
      of the first-line treatments for essential hypertension because they confer
      better cardiovascular outcomes. Losartan has been widely evaluated for the
      management of hypertension. Although some studies suggested that the blood
      pressure-lowering effect of losartan is perhaps lower than for other angiotensin
      receptor blockers, losartan has been demonstrated to be beneficial in terms of
      renal protection in patients with diabetes, heart failure resulting from either
      systolic or diastolic dysfunction, and diuretic-induced hyperuricemia. However,
      most of these data were obtained from Caucasian populations. The efficacy and
      safety of losartan in Asian populations may be different because of genetic and
      ethnic variations. Therefore, the efficacy and safety of losartan in Asian
      patients with hypertension warrant further study. 

PMID- 24672232
TI  - Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in
      patients with knee osteoarthritis: a multicenter study.
AB  - OBJECTIVE: To determine the efficacy and safety of Curcuma domestica extracts in
      pain reduction and functional improvement. METHODS: 367 primary knee
      osteoarthritis patients with a pain score of 5 or higher were randomized to
      receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks.
      The main outcomes were Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores.
      Adverse events (AEs) were also recorded. RESULTS: 185 and 182 patients were
      randomly assigned into C. domestica extracts and ibuprofen groups, respectively.
      The baseline characteristics were no different between groups. The mean of all
      WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared
      with the baseline in both groups. After using the noninferiority test, the mean
      difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC
      function scores at week 4 adjusted by values at week 0 of C. domestica extracts
      were noninferior to those for the ibuprofen group (P=0.010, P=0.018, and P=0.010,
      respectively), except for the WOMAC stiffness subscale, which showed a trend
      toward significance (P=0.060). The number of patients who developed AEs was no
      different between groups. However, the number of events of abdominal
      pain/discomfort was significantly higher in the ibuprofen group than that in the
      C. domestica extracts group (P=0.046). Most subjects (96%-97%) were satisfied
      with the treatment, and two-thirds rated themselves as improved in a global
      assessment. CONCLUSION: C. domestica extracts are as effective as ibuprofen for
      the treatment of knee osteoarthritis. The side effect profile was similar but
      with fewer gastrointestinal AE reports in the C. domestica extracts group.

PMID- 24672234
TI  - Indirect costs in chronic obstructive pulmonary disease: a review of the economic
      burden on employers and individuals in the United States.
AB  - OBJECTIVE: To review and summarize existing literature on the indirect burden of
      chronic obstructive pulmonary disease (COPD) in the US. METHODS: Medline, Scopus,
      and OvidSP databases were searched using defined search terms to identify
      relevant studies. Eligible studies were published in English between January 2000
      and April 2012 and calculated the indirect burden of COPD in a US population in
      terms of prevalence, incidence or costs of productivity loss, disability,
      morbidity, or mortality. RESULTS: Of 53 studies identified, eleven met
      eligibility criteria, with data years spanning 1987-2009. Estimates of workforce
      participation range from 56% to 69% among individuals with COPD and from 65% to
      77% among individuals without COPD. Approximately 13%-18% of those with COPD are
      limited in the amount or type of work they can do and one-third or more
      experience general activity limitation. Estimates of restricted activity days
      range from 27-63 days per year. Estimates of mean annual sick leave and/or
      disability days among employed individuals with COPD range from 1.3-19.4 days.
      Estimates of bed confinement range from 13-32 days per year. Estimated mean
      annual indirect costs were $893-$2,234/person (US dollars) with COPD ($1,521
      $3,348 in 2010 [US dollars]) and varied with the population studied, specific
      cost outcomes, and economic inputs. In studies that assessed total (direct and
      indirect) costs, indirect costs accounted for 27%-61% of total costs, depending
      on the population studied. CONCLUSIONS: COPD is associated with substantial
      indirect costs. The disease places a burden on employers in terms of lost
      productivity and associated costs and on individuals in terms of lost income
      related to absenteeism, activity limitation, and disability. Consideration of
      indirect as well as direct costs is necessary to gain a more complete view of the
      societal burden of COPD.

PMID- 24672235
TI  - Cytotoxicity of graphene oxide and graphene oxide loaded with doxorubicin on
      human multiple myeloma cells.
AB  - The purpose of this study was to evaluate the cytotoxicity of human multiple
      myeloma cells (RPMI-8226) treated with graphene oxide (GO), doxorubicin (DOX),
      and GO loaded with DOX (GO/DOX). Cell viability was determined using the Cell
      Counting Kit-8 assay and analyzing the cell cycle and cell apoptosis. Cells
      treated with GO, GO/DOX, and pure DOX for 24 hours showed a decrease in
      proliferation. GO/DOX significantly inhibited cell proliferation as compared with
      pure DOX (P<0.01). When the effects of GO were removed, there was no observed
      difference between GO/DOX and pure DOX (P>0.05). Flow cytometry analysis of
      untreated and GO-, DOX-, and GO/DOX-treated cells found no significant
      differences in the G0/G1 phase (P>0.05), while significant differences were
      observed in the total apoptotic rates (P<0.05). No significant differences
      existed in the total apoptotic rates of GO-treated and untreated cells (P>0.05).
      These findings suggest that GO caused low cytotoxicity and did not induce cell
      apoptosis or change the cell cycle in multiple myeloma cells. Moreover, GO did
      not affect the antitumor activity of DOX. In conclusion, GO would be suitable as
      an anticancer drug nanocarrier and used to treat hematological malignancies. 

PMID- 24672236
TI  - Chlorotoxin-conjugated graphene oxide for targeted delivery of an anticancer
      drug.
AB  - Current chemotherapy for glioma is rarely satisfactory due to low therapeutic
      efficiency and systemic side effects. We have developed a glioma-targeted drug
      delivery system based on graphene oxide. Targeted peptide chlorotoxin-conjugated
      graphene oxide (CTX-GO) sheets were successfully synthesized and characterized.
      Doxorubicin was loaded onto CTX-GO (CTX-GO/DOX) with high efficiency (570 mg
      doxorubicin per gram CTX-GO) via noncovalent interactions. Doxorubicin release
      was pH-dependent and showed sustained-release properties. Cytotoxicity
      experiments demonstrated that CTX-GO/DOX mediated the highest rate of death of
      glioma cells compared with free doxorubicin or graphene oxide loaded with
      doxorubicin only. Further, conjugation with chlorotoxin enhanced accumulation of
      doxorubicin within glioma cells. These findings indicate that CTX-GO is a
      promising platform for drug delivery and provide a rationale for developing a
      glioma-specific drug delivery system. 

PMID- 24672237
TI  - Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with
      metastatic breast cancer.
AB  - Although nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is approved to be
      given every 3 weeks, weekly use of this drug is becoming a new standard of care
      in patients with metastatic breast cancer (MBC). This prospective Phase II study
      was conducted to improve the efficacy of weekly nab-paclitaxel with cisplatin in
      MBC patients. Seventy-three women with recurrent or MBC were eligible for
      participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m(2) on
      day 1, day 8, and day 15, followed by cisplatin 75 mg/m(2) on day 1, repeated
      every 28 days with a maximum of 6 cycles. The primary objective was investigator
      assessed overall response rate (ORR). A high ORR of 67.1% was obtained, with
      rates of 80.6% for the first-line patients and 80% for patients not pretreated
      with taxanes. Among those who had objective responses, a large percentage of
      patients (83.7%) showed quickly remarkable tumor shrinkage during the first two
      cycles. The median progression-free and overall survival times were 9.8 and 26.9
      months, respectively. For the patients receiving first-, second-, and third-line
      therapy or beyond, median progression-free survival was 11.7, 7.7, and 7.6
      months, respectively (P=0.005). Molecular subtype was not significantly
      associated with ORR or disease progression. Grade 4 neutropenia occurred in 46
      patients (63.0%), with febrile neutropenia found in 9 patients (12.3%). Grade 3
      peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19
      patients (26.0%). Efficacy of weekly nab-paclitaxel can be improved by adding
      cisplatin. The doublet is highly effective, with quick response, manageable
      toxicity, and possible equivalence across molecular subtypes in MBC patients. 

PMID- 24672238
TI  - Improvement of gross motor and cognitive abilities by an exercise training
      program: three case reports.
AB  - BACKGROUND: This work examined the efficacy of an integrated exercise training
      program (coach and family) in three children with Down syndrome to improve their
      motor and cognitive abilities, in particular reaction time and working memory.
      METHODS: The integrated exercise training program was used in three children with
      Down syndrome, comprising two boys (M1, with a chronological age of 10.3 years
      and a mental age of 4.7 years; M2, with a chronological age of 14.6 years and a
      mental age of less than 4 years) and one girl (F1, chronological age 14.0 years
      and a mental age of less than 4 years). RESULTS: Improvements in gross motor
      ability scores were seen after the training period. Greater improvements in task
      reaction time were noted for both evaluation parameters, ie, time and omissions.
      CONCLUSION: There is a close interrelationship between motor and cognitive
      domains in individuals with atypical development. There is a need to plan
      intervention programs based on the simultaneous involvement of child and parents
      and aimed at promoting an active lifestyle in individuals with Down syndrome.

PMID- 24672239
TI  - Dissociation in schizophrenia and borderline personality disorder.
AB  - BACKGROUND: Dissociation likely plays a key role in schizophrenia and borderline
      personality disorder (BPD), although empirical studies that compare specific
      manifestations of these symptoms in schizophrenia and BPD are rare. In this
      context, the purpose of this study was to compare the occurrence of dissociative
      and other psychopathological symptoms in these disorders, and to assess the
      possible influence of antipsychotic medication on the dissociative symptoms.
      METHODS: We assessed 31 patients with schizophrenia and 36 patients with BPD.
      Dissociative symptoms were measured by the Dissociative Experiences Scale (DES),
      symptoms related to stress and traumatic experiences were assessed using the
      Trauma Symptom Checklist-40 (TSC-40), and other psychopathological symptoms were
      measured with the Health of the Nation Outcome Scales (HoNOS). We also assessed
      actual daily doses of antipsychotic medication in chlorpromazine equivalents in
      all participants. RESULTS: The results show that symptoms of traumatic stress
      measured by the TSC-40 had significantly higher scores in the BPD group. The data
      also show that dissociative symptoms (DES) were significantly correlated with
      symptoms of traumatic stress (TSC-40) and with symptoms assessed by the HoNOS.
      Remarkably significant correlations were found between levels of antipsychotic
      medication and the DES and between antipsychotic medication and the
      depersonalization/derealization component of the DES in BPD patients. CONCLUSION:
      The results support an important role of dissociative processes in schizophrenia
      and BPD and suggest a significant relationship between manifestations of
      dissociative symptoms in BPD and antipsychotic medication.

PMID- 24672240
TI  - Update on once-daily zonisamide monotherapy in partial seizures.
AB  - Zonisamide is an antiepileptic drug that is structurally different from other
      antiepileptic agents. Its long half-life, once-daily dosing, lack of induction of
      hepatic enzymes, and broad spectrum of action makes it a suitable candidate for
      monotherapy. It has been approved as monotherapy for partial onset epilepsy in
      Japan and South Korea for more than a decade, and was recently approved as
      monotherapy in Europe. In the USA, it is only approved by the US Food and Drug
      Administration for adjunctive treatment of partial onset epilepsy. In this paper,
      we briefly review the literature on zonisamide monotherapy in partial onset
      epilepsy with regard to its efficacy, safety, tolerability, and long-term side
      effects, including a recent noninferiority trial in comparison with extended
      release carbamazepine. While European regulatory agencies use noninferiority
      trials for approval of monotherapy, such a trial design does not meet the current
      regulatory requirements for approval as monotherapy in the USA. 

PMID- 24672241
TI  - A novel five-category multimodal T1-weighted and T2-weighted magnetic resonance
      imaging-based stratification system for the selection of spinal arachnoid cyst
      treatment: a 15-year experience of 81 cases.
AB  - BACKGROUND: Idiopathic spinal arachnoid cysts are rare cystic masses of the
      spinal canal generally classified as intra- or extradural, based on anatomical
      presentation. However, this system may not effectively indicate treatment.
      OBJECTIVE: To investigate the incidence, resection modality, and prognosis of
      spinal arachnoid cyst in a 15-year case series. PATIENTS AND METHODS: A
      retrospective study was conducted in 81 spinal arachnoid cyst patients
      (male:female 34:47, mean age 36.5 years, age range 6-66 years) classified using a
      novel five-category T1-weighted and T2-weighted magnetic resonance imaging (MRI)
      classification system (intramedullary, subdural extramedullary,
      subdural/epidural, intraspinal epidural, or intraspinal/extraspinal).
      Conservative treatment failed in all patients. They underwent spinal surgery
      between January 1995 and December 2010 and were followed up for 69 (range 3-187)
      months. Performance outcomes were assessed using the Fugl-Meyer (FM) scale 90
      days after operation. Recurrences and deaths were recorded. RESULTS:
      Subdural/epidural and intraspinal epidural cysts accounted for 66.7% (54 of 81)
      of patients, but exhibited relatively lower rates of postsurgical improvement
      using FM, with only 66.7% (36 of 54) of patients showing improvements. Excellent
      outcomes using the FM scale were reached in 100% (eight of eight) of
      intramedullary, intraspinal/extraspinal, and subdural extramedullary cyst
      patients, 86.7% (13 of 15) of subdural extramedullary cyst patients, and 66.7%
      (36 of 54) of epidural intraspinal cyst patients. CONCLUSION: The proposed five
      category multimodal MRI-based stratification system for spinal arachnoid cyst
      patients may more effectively allow clinicians to select the appropriate surgical
      intervention, and may help to predict outcomes.

PMID- 24672243
TI  - Medication transitions and polypharmacy in older adults following acute care.
AB  - BACKGROUND/OBJECTIVE: Medication changes at transitions of care and polypharmacy
      are growing concerns that adversely impact optimal drug use. We aimed to describe
      transitions and patterns of medication use before and 1 year after older patients
      were hospitalized for community-acquired pneumonia, the second-most common reason
      for admission in North America. MATERIALS AND METHODS: This was an analysis of a
      population-based clinical registry of patients treated in any of the six
      hospitals or seven emergency departments in Edmonton, Alberta, Canada, comprising
      2,105 patients 65 years and older with community-acquired pneumonia who had
      survived at least 1 year. The prevalence of polypharmacy (five or more unique
      prescription drugs), as well as new use and persistence of common drug classes
      were assessed. RESULTS: The mean age was 78 years (standard deviation 8 years),
      50% were female, 62% were hospitalized, and 58% had severe pneumonia. Among the
      2,105 patients, 949 (45%) were using five or more medications prior to
      hospitalization, increasing to 1,559 (74%) within 90 days postdischarge and
      remaining over 70% at 1 year. Overall, 1,690 (80%) patients newly started and
      1,553 (74%) patients stopped at least one medication in the first 90 days of
      follow-up. The prevalence of the most common drug classes (ie, cardiovascular,
      alimentary/metabolism) remained stable, with the exception of anti-infective
      agents, whereby 25% of patients were dispensed an anti-infective agent 3 months
      to 1 year after hospitalization. CONCLUSION: Most older patients with pneumonia
      are subject to polypharmacy, and almost every patient had a medication started or
      stopped during 1-year follow-up, with 25% using antibiotics again. The period
      following an episode of pneumonia represents an opportunity potentially to
      optimize pharmacotherapy.

PMID- 24672242
TI  - Therapeutic interventions to reduce the risk of progression from prediabetes to
      type 2 diabetes mellitus.
AB  - Clinical trials have demonstrated that it is possible to prevent diabetes through
      lifestyle modification, pharmacological intervention, and surgery. This review
      aims to summarize the effectiveness of these various therapeutic interventions in
      reducing the risk of progression of prediabetes to diabetes, and address the
      challenges to implement a diabetes prevention program at a community level.
      Strategies focusing on intensive lifestyle changes are not only efficient but
      cost-effective and/or cost-saving. Indeed, lifestyle intervention in people at
      high risk for type 2 diabetes mellitus (T2DM) has been successful in achieving
      sustained behavioral changes and a reduction in diabetes incidence even after the
      counseling is stopped. Although prediabetes is associated with health and
      economic burdens, it has not been adequately addressed by interventions or
      regulatory agencies in terms of prevention or disease management. Lifestyle
      intervention strategies to prevent T2DM should be distinct for different
      populations around the globe and should emphasize sex, age, ethnicity, and
      cultural and geographical considerations to be feasible and to promote better
      compliance. The translation of diabetes prevention research at a population
      level, especially finding the most effective methods of preventing T2DM in
      various societies and cultural settings remains challenging, but must be
      accomplished to stop this worldwide epidemic. 

PMID- 24672244
TI  - Association of hypertension and obesity with HIV and antiretroviral therapy in a
      rural tertiary health center in Nigeria: a cross-sectional cohort study.
AB  - BACKGROUND: There are few studies from Nigeria and Africa regarding the
      contribution of obesity and hypertension to cardiovascular risk in HIV-infected
      patients. This study investigates the prevalence of hypertension and obesity and
      their association with HIV infection and antiretroviral treatment (ART). METHODS:
      We conducted a cross-sectional cohort study in a rural tertiary health center in
      Nigeria. The data collected included demographic variables, blood pressure, body
      mass index (BMI), monthly income, educational attainment, HIV status and ART
      treatment, duration of treatment, and CD4 T-lymphocyte count. RESULTS: A total of
      403 participants met the inclusion criteria. There were 153 (38.0%) HIV-negative
      subjects (42.5% male, 57.5% female; mean age: 35.5 +/- 7.6 years), 120 (29.8%)
      HIV-positive drug-naive subjects (42.5% male, 57.5% female; mean age: 36.5 +/-
      9.1 years), and 130 (32.2%) HIV-positive subjects taking antiretroviral drugs
      (33.1% male, 66.9% female; mean age: 38.6 +/- 8.0 years). The prevalence of
      hypertension was 13.7% in HIV-negative subjects, 19.0% in HIV-positive drug-naive
      subjects, and 12.3% in HIV-positive ART subjects. The prevalence of obesity was
      15.9% in the HIV-negative group, 3% in the HIV-positive drug-naive group, and 8%
      in the HIV-positive ART group. Multivariate regression analysis showed no
      relationship between hypertension and HIV status (P=0.293) or ART status
      (P=0.587). In contrast, BMI showed a strong relationship with HIV status (odds
      ratio: 0.281; 95% confidence interval: 0.089-0.884; P=0.030) but not with ART
      status (P=0.593). BMI was a significant predictor of hypertension. CONCLUSION:
      HIV or ART status was not associated with hypertension. HIV infection was
      associated with a lower BMI, and a lower prevalence of obesity compared with HIV
      negative subjects.

PMID- 24672245
TI  - The "Pulse Time Index of Norm" highly correlates with the left ventricular mass
      index in patients with arterial hypertension.
AB  - BACKGROUND: Arterial stiffness, as measured by the pulse wave velocity (PWV), is
      recommended for routine use in clinical practice as an important parameter for
      the evaluation of cardiovascular risk.1 New 24-hour monitors (eg, with Vasotens
      technology; Petr Telegin Company, Nizhny Novgorod, Russian Federation) provide
      single PWV measurements as well as several PWV measurements over a period of 24
      hours.2 Such 24-hour pulse wave analysis led to the development of the novel
      Pulse Time Index of Norm (PTIN), which is defined as the percentage of a 24-hour
      period during which the PWV does not exceed the 10 m/second PWV threshold. The
      aim of this study is to test the new PTIN for correlation with the left
      ventricular mass index (LVMI). METHODS: Oscillometrically generated waveform
      files (n=137) used for clinical research studies were reanalyzed using the new
      2013 version of the Vasotens technology program, which enables PTIN calculations.
      RESULTS: A good correlation (r=-0.72) between the PTIN and the LVMI was shown,
      which was significantly above the blood pressure load (r=0.41). CONCLUSION: The
      PTIN generated by the Vasotens technology can be recommended as an indicator of
      end organ damage via hypertension.

PMID- 24672246
TI  - Gastrointestinal tract metastasis from tubulolobular carcinoma of the breast: a
      case report and review of the literature.
AB  - Metastasis of breast cancer into the gastrointestinal tract happens rarely. The
      diagnosis of this kind of disease is difficult because of the nonspecific
      symptoms and the long interval between primary manifestations and recurrence.
      Awareness of this condition may lead to an accurate diagnosis and an earlier
      initiation of systemic treatment, thus avoiding unnecessary surgical
      intervention. In this paper, we report a rare case of a patient with
      tubulolobular carcinoma metastases to the colon, presenting with abdominal pain,
      discomfort, and weight loss. The patient underwent radical mastectomy and
      received postoperative radiotherapy and chemotherapy. Ten years later, she
      presented with gastrointestinal tract symptoms. Surgery combined with systemic
      treatment was chosen for the colon lesion. Immunohistochemical staining suggested
      a breast origin. The patient was still living 24 months after the diagnosis of
      the metastasis. This is the fourth case report in our literature review. 

PMID- 24672247
TI  - Clusterin: a key player in cancer chemoresistance and its inhibition.
AB  - Clusterin is a heterodimeric disulfide-linked glycoprotein (449 amino acids)
      isolated in the rat prostate after castration. It is widely distributed in
      different tissues and highly conserved in species. There are two isoforms (1 and
      2) with antagonistic actions regarding apoptosis. Clusterin is implicated in a
      number of biological processes, including lipid transport, membrane recycling,
      cell adhesion, programmed cell death, and complement cascade, representing a
      truly multifunctional protein. Isoform 2 is overexpressed under cellular stress
      conditions and protects cells from apoptosis by impeding Bax actions on the
      mitochondrial membrane and exerts other protumor activities, like
      phosphatidylinositol 3-kinase/protein kinase B pathway activation, modulation of
      extracellular signal-regulated kinase 1/2 signaling and matrix metallopeptidase-9
      expression, increased angiogenesis, modulation of the nuclear factor kappa B
      pathway, among others. Its overexpression should be considered as a nonspecific
      cellular response to a wide variety of tissue insults like cytotoxic
      chemotherapy, radiation, excess of free oxygen radicals, androgen or estrogen
      deprivation, etc. A review of the recent literature strongly suggests potential
      roles for custirsen in particular, and proapoptosis treatments in general, as
      novel modalities in cancer management. Inhibition of clusterin is known to
      increase the cytotoxic effects of chemotherapeutic agents, and custirsen, a
      second-generation antisense oligonucleotide that blocks clusterin, is being
      tested in a Phase III clinical trial after successful results were achieved in
      Phase II studies. A major issue in cancer evolution that remains unanswered is
      whether clusterin represents a driving force of tumorigenesis or a late
      phenomenon after chemotherapy. This review presents preclinical data that
      encourages trials in various types of cancer other than advanced castration
      resistance prostate cancer and discusses briefly the appropriate timing for
      clusterin inhibition in the clinical context. 

PMID- 24672248
TI  - Oncogene mutational profile in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a common tumor in Southern China, but the
      oncogene mutational status of NPC patients has not been clarified. Using time-of
      flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in
      123 NPC patients. The relationships between mutational status and clinical data
      were assessed with a chi(2) or Fisher's exact test. Survival analysis was
      performed using the Kaplan-Meier method with the log-rank test. In 123 patients,
      21 (17.1%) NPC tumors were positive for mutations in eight oncogenes: six
      patients had PIK3CA mutations (4.9%), five NRAS mutations (4.1%), four KIT
      mutations (3.3%), two PDGFRA mutations (1.6%), two ABL mutations (1.6%), and one
      with simultaneous mutations in HRAS, EGFR, and BRAF (1%). Patients with mutations
      were more likely to relapse or develop metastasis than those with wild-type
      alleles (P=0.019). No differences or correlations were found in other clinical
      characteristics or in patient survival. No mutations were detected in oncogenes
      AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These
      results demonstrate an association between NPC and mutations in NRAS, KIT,
      PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and
      metastasis. 

PMID- 24672249
TI  - Long-term efficacy and safety of raltegravir in the management of HIV infection.
AB  - Raltegravir is an integrase strand-transfer inhibitor approved for the treatment
      of HIV infection. It was the first medication in a novel class of antiretroviral
      agents to be approved for use in the United States in 2007. Raltegravir exhibits
      potent activity against wild-type HIV-1, but resistance development has been
      noted through three different pathways. It is metabolized primarily through
      uridine diphosphate glucuronosyltransferase 1A1 and has a single inactive
      glucuronide metabolite. Raltegravir is not a substrate, inhibitor, or inducer of
      cytochrome P450 enzymes and exhibits low potential for drug-drug interactions;
      however, strong uridine diphosphate glucuronosyltransferase 1A1 inhibitors or
      inducers can alter the pharmacokinetics of raltegravir. It is well tolerated, and
      the most commonly reported adverse effects include headache, nausea, and
      diarrhea. Serious adverse effects with raltegravir are rare but include
      rhabdomyolysis and severe skin and hypersensitivity reactions. It has been
      approved for use in both treatment-naive and treatment-experienced patients and
      is a preferred first-line agent in both United States and European HIV treatment
      guidelines. Although initial approval was granted on 48-week data, 5-year
      clinical data have recently been published. This article reviews the data
      supporting long-term efficacy and safety of raltegravir in the treatment of HIV
      infection. 

PMID- 24672250
TI  - Comparative cost effectiveness of Coflex(r) interlaminar stabilization versus
      instrumented posterolateral lumbar fusion for the treatment of lumbar spinal
      stenosis and spondylolisthesis.
AB  - INTRODUCTION: Symptomatic chronic low back and leg pain resulting from lumbar
      spinal stenosis is expensive to treat and manage. A randomized, controlled,
      multicenter US Food and Drug Administration Investigational Device Exemption
      clinical trial assessed treatment-related patient outcomes comparing the
      Coflex(r) Interlaminar Stabilization Device, an interlaminar stabilization
      implant inserted following decompressive surgical laminotomy in the lumbar spine,
      to instrumented posterolateral fusion among patients with moderate to severe
      spinal stenosis. This study uses patient-reported outcomes and clinical events
      from the trial along with costs and expected resource utilization to determine
      cost effectiveness. METHODS: A decision-analytic model compared outcomes over 5
      years. Clinical input parameters were derived from the trial. Oswestry Disability
      Index scores were converted to utilities. Treatment patterns over 5 years were
      estimated based on claims analyses and expert opinion. A third-party payer
      perspective was used; costs (in $US 2013) and outcomes were discounted at 3%
      annually. Sensitivity analyses examined the influence of key parameters. Analyses
      were conducted using Medicare payment rates and typical commercial
      reimbursements. RESULTS: Five-year costs were lower for patients implanted with
      Coflex compared to those undergoing fusion. Average Medicare payments over 5
      years were estimated at $15,182 for Coflex compared to $26,863 for the fusion
      control, a difference of $11,681. Mean quality-adjusted life years were higher
      for Coflex patients compared to controls (3.02 vs 2.97). Results indicate that
      patients implanted with the Coflex device derive more utility, on average, than
      those treated with fusion, but at substantially lower costs. The cost advantage
      was greater when evaluating commercial insurance payments. Subgroup analyses
      found that the cost advantage for Coflex relative to fusion was even larger for
      two-level procedures compared to one-level procedures. CONCLUSION: The Coflex
      Interlaminar Stabilization Device was found to be cost effective compared to
      instrumented posterolateral fusion for treatment of lumbar spinal stenosis. It
      provided higher utility at substantially lower cost.

PMID- 24672251
TI  - Cost-effectiveness analysis of orbital atherectomy plus balloon angioplasty vs
      balloon angioplasty alone in subjects with calcified femoropopliteal lesions.
AB  - INTRODUCTION: As cost considerations become increasingly critical when selecting
      optimal endovascular treatment strategies, a cost-benefit analysis was conducted
      comparing the Diamondback 360 degrees (r) Orbital Atherectomy System (OAS)
      (Cardiovascular Systems, Inc., St Paul, MN, USA) and balloon angioplasty (BA) vs
      BA alone for treatment of calcified femoropopliteal lesions. PATIENTS AND
      METHODS: The clinical outcomes from COMPLIANCE 360 degrees , a prospective,
      multicenter, randomized study comparing OAS+BA vs BA alone for treatment of
      calcified femoropopliteal lesions, were correlated with cost data and previously
      published quality of life data. Site of service, hospital charges, and associated
      medical resource utilization were obtained from Uniform Billing statements for
      index treatments and associated revascularizations out to 1 year. Hospital costs
      were estimated using hospital-specific, procedure-specific cost-to-charge ratios.
      Length of stay and procedural data were collected from participating study sites.
      RESULTS: Twenty-five subjects with 38 lesions and 25 subjects with 27 lesions
      were randomized to the OAS+BA and BA-alone groups, respectively. Mean hospital
      charges (US$51,755 vs US$39,922) and estimated hospital costs (US$15,100 vs
      US$11,016) were higher for OAS+BA compared with BA alone (not statistically
      significant). Stent utilization was statistically significantly higher with BA
      alone treatment for all subjects (1.1 vs 0.1, P=0.001) and in the subset of
      subjects with one lesion (1.0 vs 0.1, P<0.00001). There was a significant
      difference in cost for single-lesion versus multiple-lesion treatment. Using
      costs and quality-adjusted life years (QALYs) for the single-lesion cohort, the 1
      year incremental cost of OAS+BA vs BA alone was US$549, and incremental QALY was
      0.16. This results in an incremental cost-effectiveness ratio of US$3,441, well
      below the US$50,000 threshold. CONCLUSION: One-year index procedure cost and cost
      effectiveness were comparable for OAS+BA vs BA alone. This study provides
      compelling cost-effectiveness data for using atherectomy for treatment of
      calcified femoropopliteal lesions, a longstanding challenge for peripheral artery
      disease interventionalists.

PMID- 24672252
TI  - Comparative effectiveness of liraglutide in the treatment of type 2 diabetes.
AB  - Type 2 diabetes is characterized by a progressive decline in beta cell function,
      with consequent worsening of glycemic control. The ideal antihyperglycemic
      treatment should achieve good and sustained glycemic control, with a low risk of
      hypoglycemia and no weight gain. This paper reviews the efficacy and tolerability
      of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the
      treatment of type 2 diabetes. Once-daily injection of liraglutide (at doses of
      1.2 mg and 1.8 mg), as monotherapy or in combination with one or two oral
      antihyperglycemic agents, was associated with greater improvements in glycemic
      control compared with active comparators or placebo in several controlled,
      randomized Phase III trials, including the six trials of the LEAD (Liraglutide
      Effect and Action in Diabetes) program. Liraglutide also improved beta cell
      function, body weight, systolic blood pressure, and lipid profile, thereby
      achieving many of the goals of ideal antihyperglycemic therapy. Liraglutide was
      generally well tolerated in the Phase III trials. The most common adverse events
      were nausea, vomiting, and diarrhea, usually of mild to moderate intensity. The
      observed rate of pancreatitis was low and comparable with that of the general
      diabetic population. In conclusion, although most trials were relatively short
      and focused on surrogate endpoints, liraglutide emerges as an effective and well
      tolerated treatment for type 2 diabetes, carrying a low risk of hypoglycemia,
      weight loss, and possible reduction of cardiovascular risk. 

PMID- 24672253
TI  - Optimal management of common acquired melanocytic nevi (moles): current
      perspectives.
AB  - Although common acquired melanocytic nevi are largely benign, they are probably
      one of the most common indications for cosmetic surgery encountered by
      dermatologists. With recent advances, noninvasive tools can largely determine the
      potential for malignancy, although they cannot supplant histology. Although
      surgical shave excision with its myriad modifications has been in vogue for
      decades, the lack of an adequate histological sample, the largely blind nature of
      the procedure, and the possibility of recurrence are persisting issues. Pigment
      specific lasers were initially used in the Q-switched mode, which was based on
      the thermal relaxation time of the melanocyte (size 7 MUm; 1 MUsec), which is not
      the primary target in melanocytic nevus. The cluster of nevus cells (100 MUm)
      probably lends itself to treatment with a millisecond laser rather than a
      nanosecond laser. Thus, normal mode pigment-specific lasers and pulsed ablative
      lasers (CO2/erbium [Er]:yttrium aluminum garnet [YAG]) are more suited to treat
      acquired melanocytic nevi. The complexities of treating this disorder can be
      overcome by following a structured approach by using lasers that achieve the
      appropriate depth to treat the three subtypes of nevi: junctional, compound, and
      dermal. Thus, junctional nevi respond to Q-switched/normal mode pigment lasers,
      where for the compound and dermal nevi, pulsed ablative laser (CO2/Er:YAG) may be
      needed. If surgical excision is employed, a wide margin and proper depth must be
      ensured, which is skill dependent. A lifelong follow-up for recurrence and
      melanoma is warranted in predisposed individuals, although melanoma is decidedly
      uncommon in most acquired melanocytic nevi, even though histological markers may
      be seen on evaluation. 

PMID- 24672254
TI  - Alemtuzumab in the treatment of multiple sclerosis.
AB  - Alemtuzumab (formerly known as Campath-1H) has recently been approved by the
      European Medicines Agency for highly-active, relapsing-remitting multiple
      sclerosis (MS). The molecule targets the CD52 surface glycoprotein on certain T
      cells and B cells and is thought to exert its effect in MS through a "resetting"
      of the lymphocyte population. Approval was granted on the strength of two pivotal
      studies, Comparison of Alemtuzumab and Rebif(r) Efficacy in Multiple Sclerosis
      (CARE-MS)-1 in the first-line setting and CARE-MS-2 in patients who had failed
      first-line therapy. In both studies, alemtuzumab significantly reduced the
      relapse rate compared to the comparator, interferon beta-1a (44 MUg) given
      subcutaneously three-times per week (Rebif(r)). In the first-line study,
      alemtuzumab was also found to significantly reduce the number of patients with
      sustained progression compared to interferon beta-1a therapy. Autoimmune
      disorders represent the major side effect of alemtuzumab therapy although they
      can be managed by careful monitoring and early treatment. Overall, alemtuzumab is
      likely to be a valuable addition to the neurologist's armamentarium for the
      treatment of relapsing-remitting MS. 

PMID- 24672255
TI  - Systemic sensitization with the protein allergen ovalbumin augments local
      sensitization in atopic dermatitis.
AB  - Mouse models of atopic dermatitis based on epicutaneous sensitization have shed
      light on the role of epicutaneous allergen entry in the development of
      respiratory and gastrointestinal allergy. However, the contribution of non
      cutaneous modes of sensitization to skin diseases has not been evaluated. We
      assessed if systemic ovalbumin administration, in conjunction with local
      sensitization, could prime for a robust inflammatory response. Furthermore, we
      attempted to elucidate important aspects of disease pathogenesis previously
      unaddressed in mouse models. Mice that underwent intraperitoneal ovalbumin
      sensitization prior to epicutaneous challenge demonstrated an acute (Th2
      polarized) atopic dermatitis-like phenotype upon local challenge. The
      inflammatory response was strikingly more robust than in mice that underwent
      epicutaneous sensitization alone. The lesional infiltrate contained a dendritic
      cell population that corresponded phenotypically with inflammatory dendritic
      epidermal cells of significance in human disease. Finally, in accordance with
      observations in human atopic dermatitis, there was an increase in cluster of
      differentiation (CD) 103 (alphaE subunit)-expressing CD4(+) T lymphocytes.
      However, the absence of CD103 on approximately 50% of infiltrating cells argues
      against a primary role for the alphaEbeta7 integrin in tissue homing. In
      conclusion, we present a mouse model of atopic dermatitis that reveals novel
      insights into the pathogenesis of this complex disease. 

PMID- 24672256
TI  - Role of brentuximab vedotin in the treatment of relapsed or refractory Hodgkin
      lymphoma.
AB  - Brentuximab vedotin (BV) is an antibody-drug conjugate that targets CD30-positive
      malignancies via an anti-CD30 monoclonal antibody linked to monomethyl auristatin
      E, a microtubule-disrupting agent, by a protease-cleavable linker. BV has
      received accelerated approval from the US Food and Drug Administration for the
      treatment of classical Hodgkin lymphoma that has relapsed either after autologous
      stem cell transplantation (ASCT) or after two lines of combination chemotherapy
      in patients ineligible for ASCT, and in systemic anaplastic large cell lymphoma
      after failure of at least one line of multiagent chemotherapy. Phase I studies in
      CD30-positive lymphomas have determined the maximum tolerated dose to be 1.8
      mg/kg intravenously every 21 days. In relapsed/refractory Hodgkin lymphoma, a
      pivotal Phase II study of single-agent BV showed an overall response rate of 75%,
      with 34% complete responses and a median remission duration of 20 months for
      complete responders. BV has a modest toxicity profile, with peripheral neuropathy
      as one of the most clinically significant side effects, and this is largely
      reversible. Therefore, BV is the treatment of choice for patients with
      relapsed/refractory Hodgkin lymphoma after ASCT or two standard regimens. Ongoing
      trials are evaluating the role of BV as salvage therapy prior to ASCT and for
      maintenance after ASCT for patients with relapsed/refractory disease. 

PMID- 24672258
TI  - The importance of preventive dental visits from a young age: systematic review
      and current perspectives.
AB  - BACKGROUND: Dental caries, the most common childhood chronic disease,
      disproportionately affects vulnerable parts of the population and confers
      substantial impacts to children, families, and health systems. Because efforts
      directed toward oral health promotion and disease prevention are fundamentally
      superior to dental rehabilitation secondary to disease development, early
      preventive dental visits (EPDVs) are widely advocated by professional and
      academic stakeholders. The aim of this comprehensive review was to critically
      review and summarize available evidence regarding the effectiveness of EPDVs in
      improving children's oral health outcomes. MATERIALS AND METHODS: A systematic
      literature search of the PubMed and Embase electronic databases was undertaken to
      identify peer-reviewed publications investigating the effectiveness of EPDVs on
      oral health outcomes, including clinical, behavioral, and cost end points up to
      October 30, 2013. Outcomes of the identified studies were abstracted and
      summarized independently by two investigators. RESULTS: Four manuscripts met the
      inclusion criteria and were included in the review. All studies were conducted in
      the US and employed a retrospective cohort study design using public insurance
      claims data, whereas one study matched claims files with kindergarten state
      dental surveillance data. That study found no benefit of EPDVs in future
      clinically determined dental caries levels in kindergarten. The other three
      studies found mixed support for an association of EPDVs with subsequent more
      preventive and fewer nonpreventive visits and lower nonpreventive service-related
      expenditures. Selection bias and a problem-driven dental care-seeking pattern
      were frequently articulated themes in the reviewed studies. CONCLUSION: The
      currently available evidence base supporting the effectiveness of EPDVs and the
      year 1 first dental visit recommendation is weak, and more research is warranted.
      The benefits of EPDVs before the age of 3 years are evident among children at
      high risk or with existing dental disease. However, EPDVs may be associated with
      reduced restorative dental care visits and related expenditures during the first
      years of life.

PMID- 24672260
TI  - Effectiveness of the professional who carries out the health education program:
      perinatal outcomes.
AB  - BACKGROUND: The purpose of this study was to determine whether a maternal
      education program conducted by midwives achieves better results in regard to
      maternal and newborn health than when the program is conducted by other health
      professionals. METHODS: Five hundred and twenty primiparous women attending four
      (two university) public hospitals in southern Spain in 2011 were recruited to
      participate in this prospective cohort study. Data on sociodemographic and
      obstetric variables and characteristics of newborns were collected by interviews
      and from clinical charts. Crude and logistic regression adjusted odds ratios
      (aORs) and confidence intervals (CIs) were estimated. RESULTS: A midwife was in
      charge of education for 75.4% of the 354 women who attended maternal education
      programs. Midwife-conducted programs had significantly more women attending more
      than three sessions than the programs conducted by other health professionals
      (aOR 2.85, 95% CI 1.60-5.11). Midwives achieved more active participation from
      mothers during delivery (aOR 1.96, 95% CI 1.15-3.33), more early skin-to-skin
      contact between the mother and newborn (aOR 1.79, 95% CI 1.01-3.23), more early
      breastfeeding (aOR 2.08, 95% CI 1.18-3.70), and fewer newborns with low birth
      weight (aOR 0.14, 95% CI 0.03-0.65) compared with other health professionals.
      CONCLUSION: Midwives achieve better results than other health professionals in
      regard to the health of the mother and her newborn when they are in charge of the
      maternal education program.

PMID- 24672261
TI  - Contraceptive knowledge and attitudes among women seeking induced abortion in
      Kathmandu, Nepal.
AB  - OBJECTIVE: To map the knowledge about and attitudes toward birth control methods
      among women in Kathmandu, Nepal, and to compare the results between women seeking
      an induced abortion and a control group. METHOD: This was a cross-sectional
      cohort study with matched controls. Women aged 15-49 years seeking medical care
      at the Department of Gynecology and Obstetrics at Kathmandu Medical College were
      included and interviewed. A case was defined as a woman who sought an elective
      medical or surgical abortion. A control was defined as a woman who sought medical
      care at the outpatient department or had already been admitted to the ward for
      reasons other than elective abortion. A questionnaire developed for the study -
      dealing with different demographic characteristics as well as knowledge about and
      attitudes toward contraceptives - was filled out based on the interview. RESULTS:
      A total of 153 women were included: 64 women seeking an abortion and 89 controls.
      Women seeking an abortion had been pregnant more times than the control group and
      were more likely to have been informed about contraceptives. Women with higher
      education were less likely to seek an abortion than women with lower education.
      There was no significant difference in knowledge about and attitudes toward
      contraceptives between cases and controls. The women considered highest possible
      effectiveness to be the most important feature when deciding on a birth control
      method. CONCLUSION: Women seeking abortion in Kathmandu had shorter education and
      a history of more pregnancies and deliveries than women in the control group.
      Education and counseling on sex and reproduction as well as on contraceptive
      methods probably need to be improved in Nepal to avoid unwanted pregnancies.
      Attitudes about contraceptives need to be further investigated to develop better
      and more effective methods to educate women about family planning in order to
      increase reproductive health.

PMID- 24672257
TI  - Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of
      the literature.
AB  - Commonly used chemotherapeutic agents in oncology/hematology practice, causing
      toxic peripheral neuropathy, include taxanes, platinum compounds, vinca
      alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents.
      This review paper intends to put together and discuss the spectrum of
      chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to
      highlight areas of future research to pursue on the topic. Current knowledge
      shows that the pathogenesis of CIPN still remains elusive, mostly because there
      are several sites of involvement in the peripheral nervous system. In any case,
      it is acknowledged that the dorsal root ganglia of the primary sensory neurons
      are the most common neural targets of CIPN. Both the incidence and severity of
      CIPN are clinically under- and misreported, and it has been demonstrated that
      scoring CIPN with common toxicity scales is associated with significant inter
      observer variability. Only a proportion of chemotherapy-treated patients develop
      treatment-emergent and persistent CIPN, and to date it has been impossible to
      predict high-and low-risk subjects even within groups who receive the same drug
      regimen. This issue has recently been investigated in the context of
      pharmacogenetic analyses, but these studies have not implemented a proper
      methodological approach and their results are inconsistent and not really
      clinically relevant. As such, a stringent approach has to be implemented to
      validate that information. Another open issue is that, at present, there is
      insufficient evidence to support the use of any of the already tested
      chemoprotective agents to prevent or limit CIPN. The results of comprehensive
      interventions, including clinical, neurophysiological, and pharmacogenetic
      approaches, are expected to produce a consistent advantage for both doctors and
      patients and thus allow the registration and analysis of reliable data on the
      true characteristics of CIPN, eventually leading to potential preventive and
      therapeutic interventions. 

PMID- 24672262
TI  - A fatal case of congenital pulmonary airway malformation with aspergillosis in an
      adult.
AB  - Congenital cystic adenomatoid malformation, currently referred as congenital
      pulmonary airway malformation (CPAM), is one of the rare lung malformations seen
      in adults. We report a case of a 59-year-old male with a chronic cough and
      hemoptysis that was not amenable to bronchial embolization. Further work up
      revealed cystic changes with fungal ball and type 1 CPAM. Patients with this
      condition who survive to adulthood usually suffer from recurrent respiratory
      bacterial infections. Only three cases of fungal involvement have ever been
      described. We present a fatal case, as well as the oldest patient. 

PMID- 24672263
TI  - Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous
      and oral administration to healthy volunteers.
AB  - BACKGROUND: The pharmacology of single doses of acetylsalicylic acid (ASA)
      administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was
      evaluated in a randomized, placebo-controlled, crossover study. METHODS: Blood
      and urine samples were collected before and up to 24 hours after administration
      of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of
      platelet aggregation were determined using validated techniques. RESULTS: A
      comparison between administration routes showed that the geometric mean dose
      corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area
      under the curve (AUC0-infinity/D) were higher following intravenous
      administration of ASA 500 mg compared with oral administration (estimated ratios
      were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation
      was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid
      onset of inhibition that was not observed with oral dosing. At 5 minutes after
      administration, the mean reduction in arachidonic acid-induced thromboxane B2
      synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500
      mg intravenously. In exploratory analyses, thromboxane B2 synthesis was
      significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each
      observed time point up to the first hour after administration. Concentrations of
      6-keto-prostaglandin1alpha at 5 and 20 minutes after dosing were also
      significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally.
      CONCLUSION: This study demonstrates that intravenous ASA provides more rapid and
      consistent platelet inhibition than oral ASA within the first hour after dosing.

PMID- 24672265
TI  - The exclusion of hypochromia from the iron deficiency screen.

PMID- 24672264
TI  - The ABCs of incentive-based treatment in health care: a behavior analytic
      framework to inform research and practice.
AB  - Behavior plays an important role in health promotion. Exercise, smoking
      cessation, medication adherence, and other healthy behavior can help prevent, or
      even treat, some diseases. Consequently, interventions that promote healthy
      behavior have become increasingly common in health care settings. Many of these
      interventions award incentives contingent upon preventive health-related
      behavior. Incentive-based interventions vary considerably along several
      dimensions, including who is targeted in the intervention, which behavior is
      targeted, and what type of incentive is used. More research on the quantitative
      and qualitative features of many of these variables is still needed to inform
      treatment. However, extensive literature on basic and applied behavior analytic
      research is currently available to help guide the study and practice of incentive
      based treatment in health care. In this integrated review, we discuss how
      behavior analytic research and theory can help treatment providers design and
      implement incentive-based interventions that promote healthy behavior. 

PMID- 24672267
TI  - Evaluation of intra-musclar oxygenation during exercise in humans.
AB  - Near infrared spectroscopy (NIRS) has been frequently used to assess intra
      muscular oxygenation past few decades. In recent years, refinement of NIRS
      hardware and algorithms used to convert changes in optical absorption to changes
      in concentration improved the validity of oxygenated haemoglobin (HbO2),
      deoxyhaemoglobin (Hb), myoglobin (Mb) and the oxidised copper compound of
      cytochrome aa3 , (cyt aa3 ) measurements. Subsequently, the use of NIRS to study
      the muscle oxygenation profiles during various types of exercise and to monitor
      differences in oxygenation levels in patients under various pathological
      conditions is being increased. It would be thought-provoking to combine future
      muscle studies with MRS and/or electromyography techniques to improve the
      understanding of intramuscular oxygenation. 

PMID- 24672266
TI  - Diabetes, oxidative stress and physical exercise.
AB  - Oxidative stress, an imbalance between the generation of reactive oxygen species
      and antioxidant defense capacity of the body, is closely associated with aging
      and a number of diseases including cancer, cardiovascular diseases, diabetes and
      diabetic complications. Several mechanisms may cause oxidative insult in
      diabetes, although their exact contributions are not entirely clear. Accumulating
      evidence points to many interrelated mechanisms that increase production of
      reactive oxygen and nitrogen species or decrease antioxidant protection in
      diabetic patients. In modern medicine, regular physical exercise is an important
      tool in the prevention and treatment of diseases including diabetes. Although
      acute exhaustive exercise increases oxidative stress, exercise training has been
      shown to up regulate antioxidant protection. This review aims to summarize the
      mechanisms of increased oxidative stress in diabetes and with respect to acute
      and chronic exercise. 

PMID- 24672268
TI  - Physiological effects of an ultra-cycle ride in an amateur athlete - a case
      report.
AB  - The physiological effects of ultraendurance exercise are poorly investigated. The
      present case report describes the exercise intensity of ultraendurance cycling
      and its physiological impacts on various organ functions in an amateur cyclist
      performing the Otztal Radmarathon twice en bloque in a circuit of 2 identical
      laps (distance 460 km; cumulative altitude difference 11,000 m). In a pre-race
      laboratory test the athlete's performance capacity was measured as the maximal
      aerobic power (VO2max= 70 ml.kg(-1).min(-1)), a maximal power output (5.7 W.kg(
      1)) and lactate threshold of 89%. The overall intensity during the ride was
      moderate (HRmean = 131 b.min(-1); %HRmax = 0.71) and significantly declined
      during the course of the race. Extensive biochemical laboratory testing performed
      pre- and post-race excluded major exercise-induced organ disturbances. For
      further confirmation and better understanding of the physiological effects of
      ultra-cycle events future studies of larger athlete populations are required. 

PMID- 24672269
TI  - Avulsion of the ischial tuberosity in a young soccer player: six years follow-up.
AB  - In this case a seventeen-years-old male soccer player, who sustained an injury
      while playing football, diagnosed as ischial tuberosity avulsion was reported.
      Following six-months of a conservative rehabilitation program, the athlete
      returned to his sports' activities. Six years along he had no complaints and his
      athletic performance was not deteriorated. In this case report diagnosis,
      treatment and six-years follow-up results were discussed. 

PMID- 24672270
TI  - Primary care physicians' knowledge and perceived barriers in the management of
      overweight and obesity.
AB  - OBJECTIVES: To determine the level of knowledge of primary health care physicians
      and the barriers perceived in the management of overweight and obesity in the
      Eastern Province of Saudi Arabia. SETTING: Primary health care centers in Dammam
      and Al-Khobar cities, Saudi Arabia. DESIGN: A cross-sectional study. MATERIALS
      AND METHODS: One hundred and forty-nine physicians were surveyed. Data were
      collected with a specially made anonymous, self-administrated, structured
      questionnaire with a Cronbach alpha reliability of 0.85, and content validity by
      five experts was used to measure the knowledge and barriers from several
      different aspects of care provided by primary health care centers to the
      overweight and obese. RESULTS: One hundred and thirty (87%) physicians responded.
      More than two-thirds of the respondents considered themselves as key players in
      the management of obesity. However, only one-third believed that they were well
      prepared to treat obesity. Eighty-three per cent of the respondents had a
      negative attitude toward the concept of overweight and obesity. It was noted that
      76.9% of physicians advised patients to control their weight with sport and
      exercise together with low calorie diet. Sixty percent of the respondents used
      body mass index to diagnose obesity. Seventy-two percent of respondents did not
      use weight reduction medications to treat obesity. Lack of training, poor
      administrative support, and time constraints were identified as barriers in
      managing overweight and obesity. CONCLUSION: Respondents were aware of the
      magnitude of overweight and obesity as a major public health problem in Saudi
      Arabia, and they were also aware of the correct definition of overweight and
      obesity, as well as its effect in increasing mortality. Better training is
      required to improve some areas of awareness and management of the conditions.

PMID- 24672271
TI  - Attitude of primary care physicians toward patient safety in Aseer region, Saudi
      Arabia.
AB  - OBJECTIVE: The objective of this study was to assess the attitude of physicians
      at primary health-care centers (PHCC) in Aseer region toward patient safety.
      MATERIALS AND METHODS: This study was conducted among working primary health-care
      physicians in Aseer region, Saudi Arabia, in August 2011. A self-administered
      questionnaire consisting of three parts was used; the first part was on the socio
      demographic, academic and about the work profile of the participants. The
      attitude consisting of 26 questions was assessed on a Likert scale of 7 points
      using attitude to patients safety questionnaire-III items and the last part
      concerned training on "patient safety", definition and factors that contribute to
      medical errors. Data of the questionnaire were entered and analyzed by
      Statistical Package for the Social Sciences (SPSS) version 15. RESULTS: The total
      number of participants was 228 doctors who represent about 65% of the physicians
      at PHCC, one-third of whom had attended a course on patient safety and only 52%
      of whom defined medical error correctly. The best score was given for the
      reduction of medical errors (6.2 points), followed by role of training and
      learning on patient safety (6 and 5.9 points), but undergraduate training on
      patient safety was given the least score. Confidence to report medical errors
      scored 4.6 points as did reporting the errors of other people and 5.6 points for
      being open with the supervisor about an error made. Participants agreed that
      "even the most experienced and competent doctors make errors" (5.9 points), on
      the other hand, they disagreed that most medical errors resulted from nurses'
      carelessness (3.9 points) or doctors' carelessness (4 points). CONCLUSION: This
      study showed that PHCC physicians in Aseer region had a positive attitude toward
      patient safety. Most of them need training on patient safety. Undergraduate
      education on patient safety which was considered a priority for making future
      doctors' work effective was inadequate.

PMID- 24672272
TI  - The prevalence of pterygium in Alkhobar: A hospital-based study.
AB  - OBJECTIVE: To analyze the epidemiology of pterygium in a hospital-based
      population in Alkhobar, which is located in the eastern province of Saudi Arabia.
      MATERIALS AND METHODS: This was a retrospective, non-randomized, and consecutive
      case study. Out of 88,666 patients who were seen in the ophthalmology clinic
      between January 1995 through the end of December 2010, 116 patients were
      diagnosed with advanced pterygium. The medical records of these patients were
      evaluated. RESULTS: The overall prevalence of pterygium was found to be 0.074%.
      There was no significant difference by either gender, side, or by laterality (P >
      0.05). A significant increase was noticed in the prevalence of pterygium with
      increasing age and nasal location (P < 0.05). CONCLUSION: The overall prevalence
      rate of pterygium in Alkhobar is low when compared with results reported from
      other areas of the world.

PMID- 24672273
TI  - Prevalence and associated factors of polypharmacy among adult Saudi medical
      outpatients at a tertiary care center.
AB  - OBJECTIVE: The objective of this study was to assess the prevalence of
      polypharmacy (PP) and the associated factors in medical outpatients. MATERIALS
      AND METHODS: A cross-sectional, observational, descriptive study was carried out
      in adult medical outpatients attending internal medicine clinics at King
      Abdulaziz Medical City, Riyadh, Saudi Arabia from 1 March 2009 to 31 December
      2009. PP was defined as the concomitant use of >=5 medications daily. The number
      of medications being currently taken by patient was recorded. Effect of patients'
      age, gender, educational level, number of prescribers, disease load and disease
      type on PP was assessed by multivariate analysis using Statistical Package for
      Social Sciences Incorporated (SPSS Inc) Version 18. RESULTS: Out of 766 patients
      included in the study, 683 (89%) had PP. The mean number of prescribed
      medications, oral pills and doses was 8.8, 9.6 and 12.1, respectively. Factors
      significantly associated with PP included age (>=61 years), disease load and the
      number of prescribers. Gender had no impact on PP while education beyond primary
      education significantly decreased PP. Hypertension, diabetes mellitus and
      dyslipidemia alone and as a cluster increased PP. CONCLUSION: We found an
      extremely high level of PP in medical outpatients at our tertiary care center.
      The impact of PP on medication compliance and control of underlying diseases in
      Saudi Arabia is unknown and needs to be studied at different levels of care.

PMID- 24672274
TI  - Prevalence of smoking among male secondary school students in Jeddah, Saudi
      Arabia.
AB  - OBJECTIVES: This study was conducted to examine the prevalence of smoking and
      habits of smoking among male secondary school students in Jeddah, Kingdom of
      Saudi Arabia (KSA) and to assess their knowledge and attitudes toward it.
      MATERIALS AND METHODS: A cross-sectional study was conducted in Jeddah, using a
      two-stage cluster sampling, randomly selecting 4 out of 85 government male
      secondary schools. Data were obtained through a self-administered questionnaire
      eliciting responses to questions on personal background, smoking behavior,
      knowledge, behavior, and attitude toward smoking. A total of 695 students
      responded to the questionnaires with 87.4% response rate. RESULTS: Of the studied
      group, 258 (37%) currently smoked, and of these, 83.7% had started smoking at the
      age of 14 years or less. The most common reason for smoking was the influence of
      family, especially the presence of someone at home who smoked (65, 9%) and
      friends who smoked (42.5%). Many of the students search for information on the
      risks of smoking (66.3%), and only (45.3%) knew about the bad effects of passive
      smoking on others. Two-third of the students who smoked wanted to quit smoking
      (63.2%), especially if suitable help was offered, whereas (60.9%) had tried to
      quit. While 50% of students smoked for recreation and entertainment, and (33.6%)
      had difficulty avoiding smoking in no smoking areas. CONCLUSION: A well-planned
      integrated antismoking campaign is urgently required, especially among students
      and teachers. The study revealed that the prevalence of smoking was high. This
      will contribute to an increase in smoking-related health problems in the future
      if proper preventive measures are not taken.

PMID- 24672275
TI  - Computer literacy of physicians among the hospitals of Makkah region.
AB  - BACKGROUND AND OBJECTIVES: A confidential inquiry by the Directorate General of
      Health Affairs, Makkah region, Saudi Arabia, found physicians in different
      hospitals were reluctant to enter patients' related information in electronic
      medical record systems. One of the major issues raised was that they didn't have
      the required computer literacy. Our aim, therefore, was to conduct a survey to
      highlight the computer literacy among the physicians of Makkah region. MATERIALS
      AND METHODS: This cross-sectional survey was performed from May to July 2009. A
      structured questionnaire of four A4 size paper was distributed among the
      physicians of the Makkah region working in seven different hospitals. The
      questionnaire contained questions on background knowledge of computers, i.e., (a)
      basic computer vocabulary knowledge (BCVK) (10 questions), (b) basic computer
      skills (BCS) (22 questions), (c) basic communication and internet skills (BCIS)
      (12 questions). RESULTS: Response rate of 368, i.e., 81.6% of sample size (n =
      451) was attained. The maximum response came from King Abdul Aziz Hospital
      (Taif), i.e., 79%. Overall BCVK, BCS and BCIS were the highest among the
      physicians of Alnoor Specialist Hospital, i.e., 71.3%, 91.4%, 87.7%,
      respectively. All the hospitals had a satisfactory level of BCVK, but levels of
      BCS and BCIS were above satisfactory except King Abdul Aziz Hospital (Jeddah)
      that showed a satisfactory level in BCIS. CONCLUSION: Majority of the physicians
      had a good or an excellent level of computer background knowledge that gave a
      prediction toward the issues of their non-promising attitude and beliefs about
      electronic data entry.

PMID- 24672276
TI  - Prevalence of low testosterone levels in men with type 2 diabetes mellitus: a
      cross-sectional study.
AB  - BACKGROUND: A high prevalence of low serum testosterone (LST) in men with type 2
      diabetes have been reported worldwide. The aim of this study was to determine the
      prevalence and associated factors of LST in men with type 2 diabetes. MATERIALS
      AND METHODS: This was a cross-sectional study, conducted among 1,089 men (aged 30
      70 years) with type 2 diabetes who consecutively attended a major diabetes center
      in Amman, Jordan, between August 2008 and February 2009. The patients'
      demographic characteristics were collected using a prestructured questionnaire.
      Duration of diabetes, smoking habits, presence of retinopathy, neuropathy, and
      nephropathy were collected from the medical records. All participants were asked
      to complete the Androgen Deficiency in Ageing Male (ADAM) questionnaire. Venous
      blood sample was collected to test for total testosterone (TT), free testosterone
      (FT), sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), prolactin (PRL), serum lipids, and glycosylated
      hemoglobin (HbA1c). LST was defined as TT <3 ng/ml. RESULTS: Overall, 36.5% of
      patients with diabetes had TT level <3 ng/ml and 29% had symptoms of androgen
      deficiency. Of those with serum testosterone level <3 ng/ml, 80.2% had symptoms
      of androgen deficiency, 16.9% had primary hypogonadism (HG), and 83.1% had
      secondary HG. Univariate analysis showed a significant relationship between age,
      income, education, body mass index (BMI), smoking, duration of diabetes, diabetic
      nephropathy, diabetic neuropathy, and HbA1c. Multivariate logistic regression
      analysis indicated age, income, BMI, and diabetic neuropathy as the independent
      risk factors of LST. CONCLUSIONS: The prevalence of LST among men with type 2
      diabetes is high. Age, income, BMI, and diabetic neuropathy were found to be the
      independent risk factors for LST.

PMID- 24672277
TI  - Prevalence and the relationship of oral mucosal lesions in tobacco users and
      denture wearers in the North Indian population.
AB  - AIM: The aim of the present study was to determine the prevalence and the
      relationship of oral mucosal lesions in tobacco users and denture wearers in a
      North Indian population. MATERIALS AND METHODS: The study comprised 3,749
      patients attending the Department of Oral Medicine and Radiology, Jodhpur Dental
      College General Hospital between September 2008 and December 2012, for the
      treatment of dental problems other than oral mucosal lesions. The ages ranged
      from 28 years to 83 years, with a mean age of 49.7 years. The results were
      evaluated using the Pearson Chi-square test, with Yate's correction and ANOVA
      tests. RESULTS: A total of 2,318 patients were diagnosed with lesions associated
      with the use tobacco and the wearing of dentures. The most frequently seen lesion
      was melanin pigmentation (29.9%) followed by linea alba (22.2%) and frictional
      keratosis (19.9%). Ulcers (6.1%) were the most common oral lesion seen in
      patients who wore dentures, followed by hyperplasia (4.8%). A statistically
      significant relation (P < 0.05) was established between tobacco and melanin
      pigmentation, frictional keratosis, traumatic ulcerations and leukoplakia. In
      those who wore dentures a statistically significant relation (P < 0.05) was found
      between candidiasis, traumatic ulceration and frictional keratosis. CONCLUSION:
      The results of the present study indicate that the association of frictional
      keratosis with tobacco users and wearers of dentures can help in determining the
      diagnosis and treatment plan for oral cancer. Wearers of dentures should also be
      recalled for periodic checks at regular intervals and optimum preventive measures
      implemented.

PMID- 24672278
TI  - Learning style and teaching method preferences of Saudi students of physical
      therapy.
AB  - CONTEXT: To the researchers' knowledge, there are no published studies that have
      investigated the learning styles and preferred teaching methods of physical
      therapy students in Saudi Arabia. AIM: The study was conducted to determine the
      learning styles and preferred teaching methods of Saudi physical therapy
      students. SETTINGS AND DESIGN: A cross-sectional study design. MATERIALS AND
      METHODS: Fifty-three Saudis studying physical therapy (21 males and 32 females)
      participated in the study. The principal researcher gave an introductory lecture
      to explain the different learning styles and common teaching methods. Upon
      completion of the lecture, questionnaires were distributed, and were collected on
      completion. STATISTICAL ANALYSIS USED: Percentages were calculated for the
      learning styles and teaching methods. Pearson's correlations were performed to
      investigate the relationship between them. RESULTS: More than 45 (85%) of the
      students rated hands-on training as the most preferred teaching method.
      Approximately 30 (57%) students rated the following teaching methods as the most
      preferred methods: "Advanced organizers," "demonstrations," and "multimedia
      activities." Although 31 (59%) students rated the concrete-sequential learning
      style the most preferred, these students demonstrated mixed styles on the other
      style dimensions: Abstract-sequential, abstract-random, and concrete-random.
      CONCLUSIONS: The predominant concrete-sequential learning style is consistent
      with the most preferred teaching method (hands-on training). The high percentage
      of physical therapy students whose responses were indicative of mixed learning
      styles suggests that they can accommodate multiple teaching methods. It is
      recommended that educators consider the diverse learning styles of the students
      and utilize a variety of teaching methods in order to promote an optimal learning
      environment for the students.

PMID- 24672279
TI  - Paraquat poisoning: A case report and review of literature.
AB  - Paraquat (1, r-dimethyl-4,4'-bipyridium dichloride), a brown syrupy liquid is an
      effective herbicide that has low chronic toxicity because of its rapid
      deactivation on contact with soil. A high dose of paraquat or severe poisoning
      has a poor prognosis. At present there is no specific antidote to paraquat
      poisoning, hence the need to focus on prevention and in case of exposure or
      ingestion, aggressive decontamination to prevent further absorption. Although
      uncommon, paraquat ingestion can lead to severe and often fatal toxicity.
      However, despite its widespread availability, reports of this herbicide poisoning
      in India are uncommon. 

PMID- 24672280
TI  - High Dose Thiotepa in Patients with Relapsed or Refractory Osteosarcomas:
      Experience of the SFCE Group.
AB  - Introduction. Osteosarcoma relapse has a poor prognosis, with less than 25%
      survival at 5 years. We describe the experience of the French Society of
      Paediatric Oncology (SFCE) with high dose (HD) thiotepa and autologous stem cell
      transplantation (ASCT) in 45 children with relapsed osteosarcoma. Patients and
      Methods. Between 1992 and 2004, 53 patients received HD thiotepa (900 mg/m(2))
      followed by ASCT in 6 centres. Eight patients were excluded from analysis, and we
      retrospectively reviewed the clinical radiological and anatomopathological
      patterns of the 45 remaining patients. Results. Sixteen girls and 29 boys (median
      age, 15.9 years) received HD thiotepa after initial progression of metastatic
      disease (2), first relapse (26), and second or third relapse (17). We report 12
      radiological partial responses and 9 of 31 histological complete responses.
      Thirty-two patients experienced further relapses, and 13 continued in complete
      remission after surgical resection of the residual disease. Three-year overall
      survival was 40%, and 3-year progression-free survival was 24%. Delay of relapse
      (+/- 2 years from diagnosis) was a prognostic factor (P = 0.011). No acute toxic
      serious adverse event occurred. Conclusion. The use of HD thiotepa and ASCT is
      feasible in patients with relapsed osteosarcoma. A randomized study for recurrent
      osteosarcoma between standard salvage chemotherapy and high dose thiotepa with
      stem cell rescue is ongoing. 

PMID- 24672281
TI  - Analysis of surgical site infection after musculoskeletal tumor surgery: risk
      assessment using a new scoring system.
AB  - Surgical site infection (SSI) has not been extensively studied in musculoskeletal
      tumors (MST) owing to the rarity of the disease. We analyzed incidence and risk
      factors of SSI in MST. SSI incidence was evaluated in consecutive 457 MST cases
      (benign, 310 cases and malignant, 147 cases) treated at our institution. A
      detailed analysis of the clinical background of the patients, pre- and
      postoperative hematological data, and other factors that might be associated with
      SSI incidence was performed for malignant MST cases. SSI occurred in 0.32% and
      12.2% of benign and malignant MST cases, respectively. The duration of the
      surgery (P = 0.0002) and intraoperative blood loss (P = 0.0005) was significantly
      more in the SSI group than in the non-SSI group. We established the
      musculoskeletal oncological surgery invasiveness (MOSI) index by combining 4 risk
      factors (blood loss, operation duration, preoperative chemotherapy, and the use
      of artificial materials). The MOSI index (0-4 points) score significantly
      correlated with the risk of SSI, as demonstrated by an SSI incidence of 38.5% in
      the group with a high score (3-4 points). The MOSI index score and laboratory
      data at 1 week after surgery could facilitate risk evaluation and prompt
      diagnosis of SSI. 

PMID- 24672282
TI  - Acoustic wave in a suspension of magnetic nanoparticle with sodium oleate
      coating.
AB  - The ultrasonic propagation in the water-based magnetic fluid with doubled layered
      surfactant shell was studied. The measurements were carried out both in the
      presence as well as in the absence of the external magnetic field. The thickness
      of the surfactant shell was evaluated by comparing the mean size of magnetic
      grain extracted from magnetization curve with the mean hydrodynamic diameter
      obtained from differential centrifugal sedimentation method. The thickness of
      surfactant shell was used to estimate volume fraction of the particle aggregates
      consisted of magnetite grain and surfactant layer. From the ultrasonic velocity
      measurements in the absence of the applied magnetic field, the adiabatic
      compressibility of the particle aggregates was determined. In the external
      magnetic field, the magnetic fluid studied in this article becomes acoustically
      anisotropic, i.e., velocity and attenuation of the ultrasonic wave depend on the
      angle between the wave vector and the direction of the magnetic field. The
      results of the ultrasonic measurements in the external magnetic field were
      compared with the hydrodynamic theory of Ovchinnikov and Sokolov (velocity) and
      with the internal chain dynamics model of Shliomis, Mond and Morozov
      (attenuation).

PMID- 24672283
TI  - Effect of different transport observations on inverse modeling results: case
      study of a long-term groundwater tracer test monitored at high resolution.
AB  - Conservative tracer experiments can provide information useful for characterizing
      various subsurface transport properties. This study examines the effectiveness of
      three different types of transport observations for sensitivity analysis and
      parameter estimation of a three-dimensional site-specific groundwater flow and
      transport model: conservative tracer breakthrough curves (BTCs), first temporal
      moments of BTCs (m1), and tracer cumulative mass discharge (Md) through control
      planes combined with hydraulic head observations (h). High-resolution data
      obtained from a 410-day controlled field experiment at Vandenberg Air Force Base,
      California (USA), have been used. In this experiment, bromide was injected to
      create two adjacent plumes monitored at six different transects (perpendicular to
      groundwater flow) with a total of 162 monitoring wells. A total of 133 different
      observations of transient hydraulic head, 1,158 of BTC concentration, 23 of first
      moment, and 36 of mass discharge were used for sensitivity analysis and parameter
      estimation of nine flow and transport parameters. The importance of each group of
      transport observations in estimating these parameters was evaluated using
      sensitivity analysis, and five out of nine parameters were calibrated against
      these data. Results showed the advantages of using temporal moment of
      conservative tracer BTCs and mass discharge as observations for inverse modeling.

PMID- 24672284
TI  - Peripheral Stimulus Localization by Infants of Moving Stimuli on Complex
      Backgrounds.
AB  - This study examined the effect of attention in young infants on the saccadic
      localization of dynamic peripheral stimuli presented on complex and interesting
      backgrounds. Infants at 14, 20, and 26 weeks of age were presented with scenes
      from a Sesame Street movie until fixation on a moving character occurred and then
      presented with a second segment in the scene in which the character movement
      occurred in a new location. Localization of the moving character in the new
      location was faster when the infant was engaged in attention than when
      inattentive, for scenes in which the character moved from one location to
      another, or scenes in which the character stopped moving and characters in new
      locations began moving. However, localization of the character was slower during
      attention when the first character disappeared and a different character appeared
      in a new location. We also found a decrease in the linear component of the main
      sequence in the saccade characteristics over the three testing ages, and
      attention affected the main sequence for infants at the two oldest ages. These
      results partially replicate prior findings showing that attention to a focal
      stimulus affects localization of peripheral stimuli, but suggest that the nature
      of the stimuli being localized modifies the role of attention in affecting eye
      movements to peripheral stimuli.

PMID- 24672285
TI  - Experimental Electron Density and Neutron Diffraction Studies on the Polymorphs
      of Sulfathiazole.
AB  - High resolution X-ray diffraction data on forms I-IV of sulfathiazole and neutron
      diffraction data on forms II-IV have been collected at 100 K and analyzed using
      the Atoms in Molecules topological approach. The molecular thermal motion as
      judged by the anisotropic displacement parameters (adp's) is very similar in all
      four forms. The adp of the thiazole sulfur atom had the greatest amplitude
      perpendicular to the five-membered ring, and analysis of the temperature
      dependence of the adps indicates that this is due to genuine thermal motion
      rather than a concealed disorder. A minor disorder (~1-2%) is evident for forms I
      and II, but a statistical analysis reveals no deleterious effect on the derived
      multipole populations. The topological analysis reveals an intramolecular S-O...S
      interaction, which is consistently present in all experimental topologies.
      Analysis of the gas-phase conformation of the molecule indicates two low-energy
      theoretical conformers, one of which possesses the same intramolecular S-O...S
      interaction observed in the experimental studies and the other an S-O...H-N
      intermolecular interaction. These two interactions appear responsible for
      "locking" the molecular conformation. The lattice energies of the various
      polymorphs computed from the experimental multipole populations are highly
      dependent on the exact refinement model. They are similar in magnitude to
      theoretically derived lattice energies, but the relatively high estimated errors
      mean that this method is insufficiently accurate to allow a definitive stability
      order for the sulfathiazole polymorphs at 0 K to be determined.

PMID- 24672286
TI  - Comparison of risks factors for unplanned ICU transfer after ED admission in
      patients with infections and those without infections.
AB  - BACKGROUND: The objectives of this study were to compare the risk factors for
      unplanned intensive care unit (ICU) transfer after emergency department (ED)
      admission in patients with infections and those without infections and to explore
      the feasibility of using risk stratification tools for sepsis to derive a
      prediction system for such unplanned transfer. METHODS: The ICU transfer group
      included 313 patients, while the control group included 736 patients randomly
      selected from those who were not transferred to the ICU. Candidate variables were
      analyzed for association with unplanned ICU transfer in the 1049 study patients.
      RESULTS: Twenty-four variables were associated with unplanned ICU transfer.
      Sixteen (66.7%) of these variables displayed association in patients with
      infections and those without infections. These common risk factors included
      specific comorbidities, physiological responses, organ dysfunctions, and other
      serious symptoms and signs. Several common risk factors were statistically
      independent. CONCLUSIONS: The risk factors for unplanned ICU transfer in patients
      with infections were comparable to those in patients without infections. The risk
      factors for unplanned ICU transfer included variables from multiple dimensions
      that could be organized according to the PIRO (predisposition, insult/infection,
      physiological response, and organ dysfunction) model, providing the basis for the
      development of a predictive system.

PMID- 24672287
TI  - Growth and etch rate study of low temperature anodic silicon dioxide thin films.
AB  - Silicon dioxide (SiO2) thin films are most commonly used insulating films in the
      fabrication of silicon-based integrated circuits (ICs) and microelectromechanical
      systems (MEMS). Several techniques with different processing environments have
      been investigated to deposit silicon dioxide films at temperatures down to room
      temperature. Anodic oxidation of silicon is one of the low temperature processes
      to grow oxide films even below room temperature. In the present work, uniform
      silicon dioxide thin films are grown at room temperature by using anodic
      oxidation technique. Oxide films are synthesized in potentiostatic and
      potentiodynamic regimes at large applied voltages in order to investigate the
      effect of voltage, mechanical stirring of electrolyte, current density and the
      water percentage on growth rate, and the different properties of as-grown oxide
      films. Ellipsometry, FTIR, and SEM are employed to investigate various properties
      of the oxide films. A 5.25 A/V growth rate is achieved in potentiostatic mode. In
      the case of potentiodynamic mode, 160 nm thickness is attained at 300 V. The
      oxide films developed in both modes are slightly silicon rich, uniform, and less
      porous. The present study is intended to inspect various properties which are
      considered for applications in MEMS and Microelectronics.

PMID- 24672288
TI  - Experimental and theoretical research on the compression performance of CFRP
      sheet confined GFRP short pipe.
AB  - The axial compressive strength of unidirectional FRP made by pultrusion is
      generally quite lower than its axial tensile strength. This fact decreases the
      advantages of FRP as main load bearing member in engineering structure. A
      theoretical iterative calculation approach was suggested to predict the ultimate
      axial compressive stress of the combined structure and analyze the influences of
      geometrical parameters on the ultimate axial compressive stress of the combined
      structure. In this paper, the experimental and theoretical research on the CFRP
      sheet confined GFRP short pole was extended to the CFRP sheet confined GFRP short
      pipe, namely, a hollow section pole. Experiment shows that the bearing capacity
      of the GFRP short pipe can also be heightened obviously by confining CFRP sheet.
      The theoretical iterative calculation approach in the previous paper is amended
      to predict the ultimate axial compressive stress of the CFRP sheet confined GFRP
      short pipe, of which the results agree with the experiment. Lastly the influences
      of geometrical parameters on the new combined structure are analyzed. 

PMID- 24672289
TI  - Fault tolerant mobile sensor node traversal schemes based on hexagonal coverage.
AB  - Mobile sensor nodes (MSNs) are equipped with locomotive can move around after
      having been deployed. They are equipped with limited energy. A large portion of
      energy is drained during the traversal. In order to extend the life time of a
      MSN, the traveling distance must be minimized. Region of interest (ROI) is
      covered with multiple MSNs using coverage based pattern movement. When a group of
      MSNs are deployed to cover a given ROI, all the deployed MSNs should travel an
      approximately equal distance. Otherwise, the MSN which travels longer distance
      depletes more energy compared to the MSN which travels a shorter distance. In
      this work we show that, ROI partition plays great role in hole free coverage and
      makes the MSNs have optimized movement cost with fault tolerant support. 

PMID- 24672290
TI  - Analysis of infrared signature variation and robust filter-based supersonic
      target detection.
AB  - The difficulty of small infrared target detection originates from the variations
      of infrared signatures. This paper presents the fundamental physics of infrared
      target variations and reports the results of variation analysis of infrared
      images acquired using a long wave infrared camera over a 24-hour period for
      different types of backgrounds. The detection parameters, such as signal-to
      clutter ratio were compared according to the recording time, temperature and
      humidity. Through variation analysis, robust target detection methodologies are
      derived by controlling thresholds and designing a temporal contrast filter to
      achieve high detection rate and low false alarm rate. Experimental results
      validate the robustness of the proposed scheme by applying it to the synthetic
      and real infrared sequences. 

PMID- 24672291
TI  - Off-centered stagnation point flow of a couple stress fluid towards a rotating
      disk.
AB  - An investigation has been made to study the off-centered stagnation flow of a
      couple stress fluid over a rotating disk. The model developed for the governing
      problem in the form of partial differential equations has been converted to
      ordinary differential equations with the use of suitable similarity
      transformation. The analytical approximation has been made with the most
      promising analytical approach, homotopy analysis method (HAM). The convergence
      region of the obtained solution is determined and plotted. The effects of couple
      stress and nondimensional parameters have been observed on the flows of couple
      stress fluid. Also comparison has been made with the Newtonian fluid as the
      special case of considered problem. 

PMID- 24672292
TI  - Facilitating preemptive hardware system design using partial reconfiguration
      techniques.
AB  - In FPGA-based control system design, partial reconfiguration is especially well
      suited to implement preemptive systems. In real-time systems, the deadline for
      critical task can compel the preemption of noncritical one. Besides, an
      asynchronous event can demand immediate attention and, then, force launching a
      reconfiguration process for high-priority task implementation. If the
      asynchronous event is previously scheduled, an explicit activation of the
      reconfiguration process is performed. If the event cannot be previously
      programmed, such as in dynamically scheduled systems, an implicit activation to
      the reconfiguration process is demanded. This paper provides a hardware-based
      approach to explicit and implicit activation of the partial reconfiguration
      process in dynamically reconfigurable SoCs and includes all the necessary tasks
      to cope with this issue. Furthermore, the reconfiguration service introduced in
      this work allows remote invocation of the reconfiguration process and then the
      remote integration of off-chip components. A model that offers component location
      transparency is also presented to enhance and facilitate system integration. 

PMID- 24672293
TI  - Using targeted virotherapy to treat a resistant Ewing sarcoma model: from the
      bedside to the bench and back.
AB  - Metastatic Ewing sarcoma (EWS) is often resistant to current multimodal
      chemotherapeutic regimens. Oncolytic virus therapy (OV) is a novel therapeutic
      platform whereby viruses can selectively infect as well as replicate in and kill
      tumor cells, while sparing normal tissues. The purpose of this study is to
      investigate the efficacy of the biotherapeutic oncolytic agent, vesicular
      stomatitis virus (VSVDeltaM51), to kill EWS cells that are resistant to
      conventional therapy. Our hypothesis is that systemic delivery of VSVDeltaM51 can
      demonstrate tumor-specific killing of resistant EWS cells, as well as a
      significant decrease of tumor burden in EWS bearing mice. METHODS: A biopsy
      sample was obtained from a patient with metastatic EWS and was used to establish
      a novel EWS cell line. In vitro assays evaluated the oncolytic effect of
      vesicular stomatitis virus (VSVDeltaM51) on this cell line. EWS xenograft mice
      model bearing either lung or subcutaneous tumors was established to evaluate the
      antitumor specific oncolytic effect of VSVDeltaM51 after local and systemic
      delivery. RESULTS: The established EWS cell line shared similar molecular and
      genetic traits to the patient's original tumor specimen. VSVDeltaM51 effectively
      infected and killed EWS cells in vitro. In vivo, VSVDeltaM51 selectively infected
      and killed EWS and led to significant delay in tumor growth. CONCLUSION: This
      study has been designed to implement a translational link between the bedside and
      the bench, where a specific challenging clinical scenario guided this basic
      science research. This research demonstrated that a sarcoma, which is resistant
      to current conventional standard therapies, is still susceptible to an
      alternative therapeutic platform, such as OV. Adding OV to the armamentarium of
      sarcoma treatment can enhance the future therapeutic approach towards these
      cancer patients.

PMID- 24672294
TI  - Design of pulse waveform for waveform division multiple access UWB wireless
      communication system.
AB  - A new multiple access scheme, Waveform Division Multiple Access (WDMA) based on
      the orthogonal wavelet function, is presented. After studying the correlation
      properties of different categories of single wavelet functions, the one with the
      best correlation property will be chosen as the foundation for combined waveform.
      In the communication system, each user is assigned to different combined
      orthogonal waveform. Demonstrated by simulation, combined waveform is more
      suitable than single wavelet function to be a communication medium in WDMA
      system. Due to the excellent orthogonality, the bit error rate (BER) of multiuser
      with combined waveforms is so close to that of single user in a synchronous
      system. That is to say, the multiple access interference (MAI) is almost
      eliminated. Furthermore, even in an asynchronous system without multiuser
      detection after matched filters, the result is still pretty ideal and
      satisfactory by using the third combination mode that will be mentioned in the
      study. 

PMID- 24672295
TI  - An active system for visually-guided reaching in 3D across binocular fixations.
AB  - Based on the importance of relative disparity between objects for accurate hand
      eye coordination, this paper presents a biological approach inspired by the
      cortical neural architecture. So, the motor information is coded in egocentric
      coordinates obtained from the allocentric representation of the space (in terms
      of disparity) generated from the egocentric representation of the visual
      information (image coordinates). In that way, the different aspects of the
      visuomotor coordination are integrated: an active vision system, composed of two
      vergent cameras; a module for the 2D binocular disparity estimation based on a
      local estimation of phase differences performed through a bank of Gabor filters;
      and a robotic actuator to perform the corresponding tasks (visually-guided
      reaching). The approach's performance is evaluated through experiments on both
      simulated and real data. 

PMID- 24672296
TI  - On the long time simulation of reaction-diffusion equations with delay.
AB  - For a consistent numerical method to be practically useful, it is widely accepted
      that it must preserve the asymptotic stability of the original continuous
      problem. However, in this study, we show that it may lead to unreliable numerical
      solutions in long time simulation even if a classical numerical method gives a
      larger stability region than that of the original continuous problem. Some
      numerical experiments on the reaction-diffusion equations with delay are
      presented to confirm our findings. Finally, some open problems on the subject are
      proposed. 

PMID- 24672297
TI  - Measurement of SUVs-maximum for normal region using VOI in PET/MRI and PET/CT.
AB  - The purpose of this research is to establish an overall data set associated with
      the VOI (Volume of Interest), which is available for simultaneous assessment of
      PET/MRI and PET/CT regardless of the use of contrast media. The participants as
      objects of this investigation are 26 healthy examinees in Korea, SUV
      (standardized-uptake-value)s-maximum evaluation for whole-body F-18 FDG
      (fluorodeoxyglucose) PET/MRI image using VOI of normal region has exhibited very
      significant difference to that for whole-body F-18 FDG PET/CT image (significant
      probability value (P) < 0.0001). However, there appeared high correlation between
      them in view of statistics (R-square (R) > 0.8). It is shown that one needs to
      decide SUVs-maximum for PET/MRI with the reduction of 25.0~26.4% from their
      evaluated value and needs to decide with the reduction of 28.8~29.4% in the same
      situation but with the use of contrast media. The use of SUVLBM-maximum (SUVLean
      Body Mass-maximum) is very advantageous in reading overall image of PET/CT and
      PET/MRI to medical doctors and researchers, if we consider its convenience and
      efficiency. We expect that this research enhances the level of the early stage
      accurate diagnosis with whole-body images of PET/MRI and PET/CT.

PMID- 24672298
TI  - Diagnostic performance of positron emission tomography/computed tomography using
      fluorine-18 fluorodeoxyglucose in detecting locoregional nodal involvement in
      patients with anal canal cancer: a systematic review and meta-analysis.
AB  - PURPOSE: The diagnostic performance of positron emission tomography using (18)F
      fluorodeoxyglucose (FDG-PET) in detecting nodal involvement in patients with anal
      canal cancer (ACC) has been investigated by several studies with conflicting
      results. The aim of our study is to systematically review and meta-analyze
      published data about this topic. METHODS: A comprehensive computer literature
      search of PubMed/MEDLINE, Scopus, and Embase databases was carried out on July 10
      to find relevant articles concerning the diagnostic performance of FDG-PET in
      detecting locoregional nodal involvement in patients with ACC. No language
      restriction was used. Pooled diagnostic performance on a lesion-based analysis
      was calculated. RESULTS: Seven retrospective and five prospective studies have
      been reviewed. Six studies allowed assessing pooled sensitivity; five studies
      allowed assessing pooled specificity. Sensitivity and specificity values of FDG
      PET/CT on a lesion-based analysis ranged from 31 to 100% and from 53 to 98%, with
      pooled estimates of 56% (95% CI: 45-67%) and 90% (95% CI: 86-93%), respectively.
      CONCLUSIONS: Our meta-analysis demonstrates that FDG-PET is a specific diagnostic
      tool in detecting locoregional lymph node involvement in patients with ACC. Low
      sensitivity is a major concern; however, higher sensitivity could be reached
      combining FDG-PET with MR scan.

PMID- 24672299
TI  - A study of feature combination for vehicle detection based on image processing.
AB  - Video analytics play a critical role in most recent traffic monitoring and driver
      assistance systems. In this context, the correct detection and classification of
      surrounding vehicles through image analysis has been the focus of extensive
      research in the last years. Most of the pieces of work reported for image-based
      vehicle verification make use of supervised classification approaches and resort
      to techniques, such as histograms of oriented gradients (HOG), principal
      component analysis (PCA), and Gabor filters, among others. Unfortunately,
      existing approaches are lacking in two respects: first, comparison between
      methods using a common body of work has not been addressed; second, no study of
      the combination potentiality of popular features for vehicle classification has
      been reported. In this study the performance of the different techniques is first
      reviewed and compared using a common public database. Then, the combination
      capabilities of these techniques are explored and a methodology is presented for
      the fusion of classifiers built upon them, taking into account also the vehicle
      pose. The study unveils the limitations of single-feature based classification
      and makes clear that fusion of classifiers is highly beneficial for vehicle
      verification. 

PMID- 24672300
TI  - Clinicopathological characteristics and outcomes of Chinese patients with scanty
      immune deposits lupus nephritis: a large cohort study from a single center.
AB  - OBJECTIVE: To assess clinicopathological characteristics of lupus nephritis
      patients with scanty immune deposits. METHODS: The data of patients with scanty
      immune deposits lupus nephritis were retrospectively analyzed. Plasma ANCA and
      complement components were detected. RESULTS: Among 316 cases with renal biopsy
      proven lupus nephritis, 40 cases were diagnosed as scanty immune deposits. There
      were significantly higher value of serum creatinine (P = 0.002) and lower
      hemoglobin level (P = 0.009) and higher score of cellular crescents (P = 0.015)
      in scanty immune deposits group compared with immune complex deposits group. The
      frequency of positive plasma ANCA was significantly higher in scanty immune
      deposits group than that in immune complex deposits group (52.5% versus 10.1%, P
      < 0.001). As for comparisons of plasma complement components, there were
      significantly higher levels of C1q (P = 0.005) and Bb (P = 0.02) and lower level
      of factor H (P = 0.003) in scanty immune deposits group. The ratio of treatment
      failure was significantly higher in scanty immune deposits group than that in
      immune deposits group (42.5% versus 19.20%, P = 0.001). The renal outcomes were
      similar between the two groups. CONCLUSIONS: Patients with scanty immune deposits
      lupus nephritis had more severe kidney damage. ANCA and activation of complement
      alternative pathway might be involved in the pathogenesis of the disease.

PMID- 24672301
TI  - Total lip reconstruction with tendinofasciocutaneous radial forearm flap.
AB  - INTRODUCTION: Squamous cell carcinoma is a common tumour of lower lip. Small
      defects created by surgical resection may be readily reconstructed by linear
      closure or with local flaps. However, large tumours resection often results with
      microstomia and oral incompetence, drooling, and speech incomprehension. The goal
      of this study is to describe our experience with composite free radial forearm
      palmaris longus tendon flap for total or near total lower lip reconstruction.
      PATIENTS AND METHODS: This procedure was used in 5 patients with 80-100% lip
      defect resulting from Squamous cell carcinoma. Patients' age ranged from 46 to 82
      years. They are three male patients and two female. In 3 cases chin skin was
      reconstructed as well and in one case a 5 cm segment of mandible was
      reconstructed using radius bone. In one case where palmaris longus was missing
      hemi-flexor carpi radialis tendon was used instead. All patients tolerated the
      procedure well. RESULTS: All flaps totally survived. No patient suffered from
      drooling. All patients regained normal diet and normal speech. Cosmetic result
      was fair to good in all patients accept one. CONCLUSION: We conclude that tendino
      fasciocutaneous radial forearm flap for total lower lip reconstruction is safe.
      Functional and aesthetic result approaches reconstructive goals.

PMID- 24672302
TI  - Theoretical analysis and characterization of multi-islands single-electron
      devices with applications.
AB  - A two- (2D) and three-dimensional (3D) multiple-tunnel junctions array is
      investigated. Device structure and electrical characteristics are described. We
      present a comparison of carriers transport through devices based on polymetallic
      grains based on master equation and the orthodox theory. The Coulomb blockade
      effect of 2D and 3D arrays is observed at low and high temperatures. The
      conduction mechanism is handled by the tunnel effect, and we adopt in addition
      the thermionic and Fowler-Nordheim emissions. Numerical simulation results
      focused on flash-memory and photodetector applications. Memory characteristics
      such as program/erase select gate operation are demonstrated in 2D devices. Also
      3D array scheme is discussed for the high-density NCs scalable for photodetector
      application. 

PMID- 24672303
TI  - The non-relativistic limit for the e-MHD equations.
AB  - We investigate the non-relativistic limit for the e-MHD equations in a three
      dimension unit periodic torus. With the prepared initial data, our result shows
      that the small parameter problems have unique solutions existing in the finite
      time interval where the corresponding limit problems (incompressible Euler
      equations) have smooth solutions. Moreover, the formal limit is rigorously
      justified. 

PMID- 24672304
TI  - Analysis and experimental verification of new power flow control for grid
      connected inverter with LCL filter in microgrid.
AB  - Microgrid is an effective way to integrate the distributed energy resources into
      the utility networks. One of the most important issues is the power flow control
      of grid-connected voltage-source inverter in microgrid. In this paper, the small
      signal model of the power flow control for the grid-connected inverter is
      established, from which it can be observed that the conventional power flow
      control may suffer from the poor damping and slow transient response. While the
      new power flow control can mitigate these problems without affecting the steady
      state power flow regulation. Results of continuous-domain simulations in MATLAB
      and digital control experiments based on a 32-bit fixed-point TMS320F2812 DSP are
      in good agreement, which verify the small signal model analysis and effectiveness
      of the proposed method. 

PMID- 24672305
TI  - Valuation of endowment-insurance equity-linked contracts for stocks with exotic
      dynamics.
AB  - We consider the fair martingale prize of insurance contracts with benefit
      received either at the insurer's demise or at maturity. We show how to modify the
      dynamics of the underlying so as to incorporate the possibility that the traded
      stock has a strong support at some level. The resulting dynamics is integrated
      and the fair prize of several natural endowment-insurance contracts is obtained. 

PMID- 24672306
TI  - High level aminoglycoside resistance and distribution of aminoglycoside resistant
      genes among clinical isolates of Enterococcus species in Chennai, India.
AB  - Enterococci are nosocomial pathogen with multiple-drug resistance by intrinsic
      and extrinsic mechanisms. Aminoglycosides along with cell wall inhibitors are
      given clinically for treating enterococcal infections. 178 enterococcal isolates
      were analyzed in this study. E. faecalis is identified to be the predominant
      Enterococcus species, along with E. faecium, E. avium, E. hirae, E. durans, E.
      dispar and E. gallinarum. High level aminoglycoside resistance (HLAR) by MIC for
      gentamicin (GM), streptomycin (SM) and both (GM + SM) antibiotics was found to be
      42.7%, 29.8%, and 21.9%, respectively. Detection of aminoglycoside modifying
      enzyme encoding genes (AME) in enterococci was identified by multiplex PCR for
      aac(6')-Ie-aph(2'')-Ia; aph(2'')-Ib; aph(2'')-Ic; aph(2'')-Id and aph(3')-IIIa
      genes. 38.2% isolates carried aac(6')-Ie-aph(2'')-Ia gene and 40.4% isolates
      carried aph(3')-IIIa gene. aph(2'')-Ib; aph(2'')-Ic; aph(2'')-Id were not
      detected among our study isolates. aac(6')-Ie-aph(2'')-Ia and aph(3')-IIIa genes
      were also observed in HLAR E. durans, E. avium, E. hirae, and E. gallinarum
      isolates. This indicates that high level aminoglycoside resistance genes are
      widely disseminated among isolates of enterococci from Chennai. 

PMID- 24672307
TI  - Fixed point results for generalized Chatterjea type contractive conditions in
      partially ordered G-metric spaces.
AB  - In the framework of ordered G-metric spaces, fixed points of maps that satisfy
      the generalized (psi, phi)-Chatterjea type contractive conditions are obtained.
      The results presented in the paper generalize and extend several well known
      comparable results in the literature. 

PMID- 24672308
TI  - Stable sheaves on a smooth quadric surface with linear Hilbert bipolynomials.
AB  - We investigate the moduli spaces of stable sheaves on a smooth quadric surface
      with linear Hilbert bipolynomial in some special cases and describe their
      geometry in terms of the locally free resolution of the sheaves. 

PMID- 24672309
TI  - Social network supported process recommender system.
AB  - Process recommendation technologies have gained more and more attention in the
      field of intelligent business process modeling to assist the process modeling.
      However, most of the existing technologies only use the process structure
      analysis and do not take the social features of processes into account, while the
      process modeling is complex and comprehensive in most situations. This paper
      studies the feasibility of social network research technologies on process
      recommendation and builds a social network system of processes based on the
      features similarities. Then, three process matching degree measurements are
      presented and the system implementation is discussed subsequently. Finally,
      experimental evaluations and future works are introduced. 

PMID- 24672310
TI  - Finite element solution of unsteady mixed convection flow of micropolar fluid
      over a porous shrinking sheet.
AB  - The objective of this investigation is to analyze the effect of unsteadiness on
      the mixed convection boundary layer flow of micropolar fluid over a permeable
      shrinking sheet in the presence of viscous dissipation. At the sheet a variable
      distribution of suction is assumed. The unsteadiness in the flow and temperature
      fields is caused by the time dependence of the shrinking velocity and surface
      temperature. With the aid of similarity transformations, the governing partial
      differential equations are transformed into a set of nonlinear ordinary
      differential equations, which are solved numerically, using variational finite
      element method. The influence of important physical parameters, namely, suction
      parameter, unsteadiness parameter, buoyancy parameter and Eckert number on the
      velocity, microrotation, and temperature functions is investigated and analyzed
      with the help of their graphical representations. Additionally skin friction and
      the rate of heat transfer have also been computed. Under special conditions, an
      exact solution for the flow velocity is compared with the numerical results
      obtained by finite element method. An excellent agreement is observed for the two
      sets of solutions. Furthermore, to verify the convergence of numerical results,
      calculations are conducted with increasing number of elements. 

PMID- 24672312
TI  - Constraint violations in stochastically generated data: detection and correction
      strategies.
AB  - We consider the generation of stochastic data under constraints where the
      constraints can be expressed in terms of different parameter sets. Obviously, the
      constraints and the generated data must remain the same over each parameter set.
      Otherwise, the parameters and/or the generated data would be inconsistent. We
      consider how to avoid or detect and then correct such inconsistencies under three
      proposed classifications: (1) data versus characteristic parameters, (2) macro-
      versus microconstraint scopes, and (3) intra- versus intervariable relationships.
      We propose several strategies and a heuristic for generating consistent
      stochastic data. Experimental results show that these strategies and heuristic
      generate more consistent data than the traditional discard-and-replace methods.
      Since generating stochastic data under constraints is a very common practice in
      many areas, the proposed strategies may have wide-ranging applicability. 

PMID- 24672311
TI  - Shedding light on the controversy surrounding the temporal decline in human sperm
      counts: a systematic review.
AB  - We systematically examined the evidence of declining sperm counts and the
      hypothesis that an increased exposure to environmental pollutants is responsible
      for such decline. Search engines, including PUBMED, MEDLINE, EMBASE, BIOSIS, and
      Cochrane library, were used to identify epidemiologic studies published from 1985
      to 2013. We concluded that there is no enough evidence to confirm a worldwide
      decline in sperm counts. Also, there seems to be no scientific truth of a
      causative role for endocrine disruptors in the temporal decline of sperm
      production. Such assumptions are based on few meta-analyses and retrospective
      studies, while other well-conducted researches could not confirm these findings.
      We acknowledge that difficult-to-control confounding factors in the highly
      variable nature of semen, selection criteria, and comparability of populations
      from different time periods in secular-trend studies, the quality of laboratory
      methods for counting sperm, and apparently geographic variations in semen quality
      are the main issues that complicate the interpretation of the available evidence.
      Owing to the importance of this subject and the uncertainties still prevailing,
      there is a need not only for continuing monitoring of semen quality, reproductive
      hormones, and xenobiotics, but also for a better definition of fecundity. 

PMID- 24672313
TI  - An adaptive motion estimation scheme for video coding.
AB  - The unsymmetrical-cross multihexagon-grid search (UMHexagonS) is one of the best
      fast Motion Estimation (ME) algorithms in video encoding software. It achieves an
      excellent coding performance by using hybrid block matching search pattern and
      multiple initial search point predictors at the cost of the computational
      complexity of ME increased. Reducing time consuming of ME is one of the key
      factors to improve video coding efficiency. In this paper, we propose an adaptive
      motion estimation scheme to further reduce the calculation redundancy of
      UMHexagonS. Firstly, new motion estimation search patterns have been designed
      according to the statistical results of motion vector (MV) distribution
      information. Then, design a MV distribution prediction method, including
      prediction of the size of MV and the direction of MV. At last, according to the
      MV distribution prediction results, achieve self-adaptive subregional searching
      by the new estimation search patterns. Experimental results show that more than
      50% of total search points are dramatically reduced compared to the UMHexagonS
      algorithm in JM 18.4 of H.264/AVC. As a result, the proposed algorithm scheme can
      save the ME time up to 20.86% while the rate-distortion performance is not
      compromised. 

PMID- 24672314
TI  - Fabrication of CPW-fed fractal antenna for UWB applications with Omni-directional
      patterns.
AB  - Novel and compact CPW-fed antennas are proposed comprised of a fractal patch and
      modified ground-plane. The ground-plane is truncated at the center and includes
      dielectric notches at its side to enhance the antenna's impedance bandwidth. The
      dimensions of the notches effectively control the upper and lower band edges of
      the antenna. The optimized antenna operates across 2.95-12.81 GHz for S11 <= -10
      dB. Omnidirectional radiation pattern is achieved over the full UWB frequency
      range. The miniaturized antenna has a total size of 14 * 18 * 1 mm(3). The
      characteristics of the proposed antenna are suitable for UWB wireless
      communication requiring low profile antennas.

PMID- 24672315
TI  - Enhanced butanol production by Clostridium acetobutylicum NCIMB 13357 grown on
      date fruit as carbon source in P2 medium.
AB  - The production of biobutanol was studied by the cultivation of Clostridium
      acetobutylicum NCIMB 13557 in P2 medium including date fruit as the sole
      substrate. The effect of P2 medium and the effect of different concentrations of
      date fruit ranging from 10 to 100 g/L on biobutanol production were investigated.
      Anaerobic batch culture was carried out at 35  degrees C incubation temperature
      and pH 7.0 +/- 0.2 for 72 h. Experimental results showed that the lowest yield of
      biobutanol and acetone-butanol-ethanol (ABE) was 0.32 and 0.35 gram per gram of
      carbohydrate consumed (g/g), respectively, when an initial date fruit
      concentration of 10 g/L was utilized. At this fruit date concentration a
      biobutanol production value of 1.56 g/L was obtained. On the other hand, the
      maximum yield of biobutanol (0.48 g/g) and ABE (0.63 g/g) was produced at 50 g/L
      date fruit concentration with a biobutanol production value as high as 11 g/L.
      However, when a higher initial date fruit concentration was used, biobutanol and
      ABE production decreased to reach the yield of 0.22 g/g and 0.35 g/g,
      respectively, where 100 g/L date fruit was used. Similar results also revealed
      that 10.03 g/L biobutanol was produced using 100 g/L date fruit.

PMID- 24672317
TI  - Characterization of toxic metals in tobacco, tobacco smoke, and cigarette ash
      from selected imported and local brands in Pakistan.
AB  - In this study, concentrations of Cd, Ni, Pb, and Cr were determined in tobacco,
      tobacco smoke-condensate, and cigarette ash for selected brands used in Pakistan.
      Smoking apparatus was designed for metal extraction from cigarette smoke. Samples
      were digested through microwave digester and then analyzed by flame atomic
      absorption spectrophotometer (FAAS). Higher concentration of Ni was detected in
      imported brands than the counterparts in the local brands. Pb levels were however
      higher in local brands while significant concentration of Cd was observed in both
      brands. For Cr, the level in tobacco of local brands was higher than their
      emitted smoke, whereas imported brands showed higher level in smoke than in
      tobacco. The cigarette ash retained 65 to 75% of the metal and about 25 to 30%
      went into the body. While this study revealed the serious requirement to
      standardize the manufacturing of tobacco products, more importantly is the urgent
      need for stronger enforcements to put in place to alert the general population
      about the hazardous effects of cigarettes and the health risks associated with
      these toxic metals. 

PMID- 24672316
TI  - Spinal fusion in the next generation: gene and cell therapy approaches.
AB  - Bone fusion represents a challenge in the orthopedics practice, being especially
      indicated for spine disorders. Spinal fusion can be defined as the bony union
      between two vertebral bodies obtained through the surgical introduction of an
      osteoconductive, osteoinductive, and osteogenic compound. Autogenous bone graft
      provides all these three qualities and is considered the gold standard. However,
      a high morbidity is associated with the harvest procedure. Intensive research
      efforts have been spent during the last decades to develop new approaches and
      technologies for successful spine fusion. In recent years, cell and gene
      therapies have attracted great interest from the scientific community. The
      improved knowledge of both mesenchymal stem cell biology and osteogenic molecules
      allowed their use in regenerative medicine, representing attractive approaches to
      achieve bone regeneration also in spinal surgery applications. In this review we
      aim to describe the developing gene- and cell-based bone regenerative approaches
      as promising future trends in spine fusion. 

PMID- 24672318
TI  - Apathy in Alzheimer's disease: any effective treatment?
AB  - OBJECTIVE: This review has evaluated the effectiveness of pharmacological
      treatment of apathy in patients with Alzheimer's disease (AD). METHODS: A
      systematic literature search was conducted on published clinical trials assessing
      the effects of pharmacological treatment on apathy in AD over the last 10 years.
      RESULTS: Fourteen studies considered of good quality were included in the
      analysis (4 randomized controlled trials, 9 open-label studies, and 1
      retrospective analysis). Cholinesterase inhibitors were investigated in 9
      studies, monoaminergic compounds such as methylphenidate and modafinil in two
      trials and one trial, respectively, and Ginkgo biloba (EGb 761 extract) and
      citalopram in one study each. Cholinesterase inhibitors did not show statistical
      significant effect in 1 RCT study but were associated to improvement in 3 open
      label studies. Methylphenidate elicited a small but significant activity
      accompanied by relevant side effects such as high blood pressure, cough, and
      osteoarticular pain. EGb 761 was well tolerated and countered apathy. Other
      treatments induced modest improvements or were ineffective. CONCLUSIONS: Apathy
      treatment remains a challenge and there is no evident advantage of any specific
      pharmacotherapy tested so far. The development of controlled studies according to
      updated guidelines for the diagnosis of apathy in patients with AD is desirable.

PMID- 24672319
TI  - Evaluation of the cytotoxic effects of CAM therapies: an in vitro study in normal
      kidney cell lines.
AB  - The purpose of this current study was to justify the incorporation of
      complementary and alternate medicine (CAM) in current cancer treatments. The
      major drawback of anticancer drugs is their nonselective killing, which
      ultimately leads to attrition of normal cells. Keeping this as the foundation of
      our study, we made an effort to compare the cytotoxicity associated with a known
      chemotherapeutic drug 5-Fluorouracil (5-FU), with certain CAM therapies
      previously reported to have anticancer activity. The parameters chosen for the
      study were based on antiproliferative and cytotoxic effects on normal, kidney
      epithelial cells (NRK-52E). The MTT assay, colony formation assay, DNA
      fragmentation, and differential staining using AO/EB, following treatment with
      either 5-FU or CAM therapies, were performed. The CAM therapies under study were
      various extracts of wheatgrass, roots of Achyranthes aspera (AA), mushroom
      extracts (Pleurotus ostreatus, Macrolepiota procera, and Auricularia polytricha),
      and a homeopathic drug, Ruta graveolens (Ruta). The results showed that treatment
      of normal cells with the CAM therapies led to minimum cell damage in comparison
      to 5-FU. This evidence-based study will lead to greater acceptance of alternative
      therapies against cancer. 

PMID- 24672320
TI  - Anthelmintic activity of crude extract and essential oil of Tanacetum vulgare
      (Asteraceae) against adult worms of Schistosoma mansoni.
AB  - Schistosomiasis, a parasitic disease caused by trematode flatworms of the genus
      Schistosoma, affects more than 200 million people worldwide, and its control is
      dependent on a single drug, praziquantel. Tanacetum vulgare (Asteraceae) is used
      in folk medicine as a vermifuge. This study aimed to investigate the in vitro
      schistosomicidal activity of the crude extract (TV) and the essential oil (TV-EO)
      from the aerial parts of T. vulgare. TV-EO was obtained by hydrodistillation and
      analyzed by GC/MS, which allowed the identification of beta-thujone (84.13%) as
      the major constituent. TV and TV-EO, at 200 MUg/mL, decreased motor activity and
      caused 100% mortality of all adult worms. At 100 and 50 MUg/mL, only TV caused
      death of all adult worms, while TV-EO was inactive. TV (200 MUg/mL) was also able
      to reduce viability and decrease production of developed eggs. Confocal laser
      scanning microscopy showed morphological alterations in the tegument of the S.
      mansoni surface after incubation with TV (50 and 100 MUg/mL). Quantitative
      analysis on the schistosomes tegument showed that TV caused changes in the
      numbers of tubercles of S. mansoni male worms in a dose-dependent manner. The
      findings suggest that T. vulgare is a potential source of schistosomicidal
      compounds.

PMID- 24672321
TI  - Optimization and validation of indirect ELISA using truncated TssB protein for
      the serodiagnosis of glanders amongst equines.
AB  - OBJECTIVE: To express truncated TssB protein of Burkholderia mallei and to
      evaluate its diagnostic efficacy for serological detection of glanders among
      equines. MATERIALS AND METHODS: In an attempt to develop recombinant protein
      based enzyme-linked immunosorbent assay (ELISA), N-terminal 200 amino acid
      sequences of B. mallei TssB protein-a type 6 secretory effector protein--were
      expressed in prokaryotic expression system. Diagnostic potential of recombinant
      TssB protein was evaluated in indirect ELISA using a panel of glanders positive
      (n = 49), negative (n = 30), and field serum samples (n = 1811). Cross-reactivity
      of the assay was assessed with equine disease control serum and human melioidosis
      positive serum. RESULTS: In comparison to CFT, diagnostic sensitivity and
      specificity of ELISA were 99.7% and 100%, respectively. CONCLUSIONS: The indirect
      ELISA method using the truncated TssB offered safer and more rapid and efficient
      means of serodiagnosis of glanders in equines. These data highlight the use of
      TssB as potential diagnostic antigen for serological diagnosis of glanders.

PMID- 24672322
TI  - Tumor necrosis factor-alpha as a diagnostic marker for neonatal sepsis: a meta
      analysis.
AB  - Neonatal sepsis (NS) is an important cause of mortality in newborns and life
      threatening disorder in infants. The meta-analysis was performed to investigate
      the diagnosis value of tumor necrosis factor-alpha (TNF-alpha ) test in NS. Our
      collectible studies were searched from PUBMED, EMBASE, and the Cochrane Library
      between March 1994 and August 2013. Accordingly, 347 studies were collected
      totally, in which 15 articles and 23 trials were selected to study the NS in our
      meta-analysis. The TNF-alpha test showed moderate accuracy of the diagnosis of NS
      both in early-onset neonatal sepsis (sensitivity = 0.66, specificity = 0.76, Q* =
      0.74) and in late-onset neonatal sepsis (sensitivity = 0.68, specificity = 0.89,
      Q* = 0.87). We also found the northern hemisphere group in the test has higher
      sensitivity (0.84) and specificity (0.83). A diagnostic OR analysis found that
      the study population may be the major reason for the heterogeneity. Accordingly,
      we suggest that TNF-alpha is also a valuable marker in the diagnosis of NS.

PMID- 24672323
TI  - A supervised approach to predict the hierarchical structure of conversation
      threads for comments.
AB  - User-generated texts such as comments in social media are rich sources of
      information. In general, the reply structure of comments is not publicly
      accessible on the web. Websites present comments as a list in chronological
      order. This way, some information is lost. A solution for this problem is to
      reconstruct the thread structure (RTS) automatically. RTS predicts a semantic
      tree for the reply structure, useful for understanding users' behaviours and
      facilitating follow of the actual conversation streams. This paper works on RTS
      task in blogs, online news agencies, and news websites. These types of websites
      cover various types of articles reflecting the real-world events. People with
      different views participate in arguments by writing comments. Comments express
      opinions, sentiments, or ideas about articles. The reply structure of threads in
      these types of websites is basically different from threads in the forums, chats,
      and emails. To perform RTS, we define a set of textual and nontextual features.
      Then, we use supervised learning to combine these features. The proposed method
      is evaluated on five different datasets. The accuracy of the proposed method is
      compared with baselines. The results reveal higher accuracy for our method in
      comparison with baselines in all datasets. 

PMID- 24672324
TI  - Hydrothermal synthesis and acetylene sensing properties of variety low
      dimensional zinc oxide nanostructures.
AB  - Various morphologies of low dimensional ZnO nanostructures, including spheres,
      rods, sheets, and wires, were successfully synthesized using a simple and facile
      hydrothermal method assisted with different surfactants. Zinc acetate dihydrate
      was chosen as the precursors of ZnO nanostructures. We found that polyethylene
      glycol (PEG), polyvinylpyrrolidone (PVP), glycine, and ethylene glycol (EG) play
      critical roles in the morphologies and microstructures of the synthesized
      nanostructures, and a series of possible growth processes were discussed in
      detail. Gas sensors were fabricated using screen-printing technology, and their
      sensing properties towards acetylene gas (C2H2), one of the most important arc
      discharge characteristic gases dissolved in oil-filled power equipments, were
      systematically measured. The ZnO nanowires based sensor exhibits excellent C2H2
      sensing behaviors than those of ZnO nanosheets, nanorods, and nanospheres,
      indicating a feasible way to develop high-performance C2H2 gas sensor for
      practical application. 

PMID- 24672325
TI  - A novel photosynthesis of carboxymethyl starch-stabilized silver nanoparticles.
AB  - The water soluble photoinitiator (PI) 4-(trimethyl ammonium methyl) benzophenone
      chloride is used for the first time in the synthesis of silver nanoparticles
      (AgNPs). A new green synthesis method involves using PI/UV system, carboxymethyl
      starch (CMS), silver nitrate, and water. A mechanism of the reduction of silver
      ions to AgNPs by PI/UV system as well as by the newly born aldehydic groups was
      proposed. The synthesis process was assessed by UV-vis spectra and TEM of AgNPs
      colloidal solution. The highest absorbance was obtained using CMS, PI and AgNO3
      concentrations of 10 g/L, 1 g/L, and 1 g/L, respectively; 40  degrees C; 60 min;
      pH 7; and a material : liquor ratio 1 : 20. AgNPs so-obtained were stable in
      aqueous solution over a period of three weeks at room temperature (~25  degrees
      C) and have round shape morphology. The sizes of synthesized AgNPs were in the
      range of 1-21 nm and the highest counts % of these particles were for particles
      of 6-10 and 1-3 nm, respectively.

PMID- 24672326
TI  - P-bRS: a physarum-based routing scheme for wireless sensor networks.
AB  - Routing in wireless sensor networks (WSNs) is an extremely challenging issue due
      to the features of WSNs. Inspired by the large and single-celled amoeboid
      organism, slime mold Physarum polycephalum, we establish a novel selecting next
      hop model (SNH). Based on this model, we present a novel Physarum-based routing
      scheme (P-bRS) for WSNs to balance routing efficiency and energy equilibrium. In
      P-bRS, a sensor node can choose the proper next hop by using SNH which
      comprehensively considers the distance, energy residue, and location of the next
      hop. The simulation results show how P-bRS can achieve the effective trade-off
      between routing efficiency and energy equilibrium compared to two famous
      algorithms. 

PMID- 24672327
TI  - F-expansion method and new exact solutions of the Schrodinger-KdV equation.
AB  - F-expansion method is proposed to seek exact solutions of nonlinear evolution
      equations. With the aid of symbolic computation, we choose the Schrodinger-KdV
      equation with a source to illustrate the validity and advantages of the proposed
      method. A number of Jacobi-elliptic function solutions are obtained including the
      Weierstrass-elliptic function solutions. When the modulus m of Jacobi-elliptic
      function approaches to 1 and 0, soliton-like solutions and trigonometric-function
      solutions are also obtained, respectively. The proposed method is a
      straightforward, short, promising, and powerful method for the nonlinear
      evolution equations in mathematical physics. 

PMID- 24672328
TI  - Formulation and evaluation of guggul lipid nanovesicles for transdermal delivery
      of aceclofenac.
AB  - CONTEXT: Most new drugs have low water solubility and liposome is an important
      formulation to administer such drugs; however, it is quite unstable and has
      negligible systemic absorption. OBJECTIVE: Aceclofenac nanovesicles were made
      using guggul lipid for formulating stable transdermal formulation. MATERIALS AND
      METHODS: Guggul lipid was formulated into vesicles along with cholesterol and
      dicetyl phosphate using film hydration method. The formulations were analyzed for
      physicochemical properties and stability. Then its skin permeation and anti
      inflammatory activity were determined. RESULTS: Both categories of vesicles (PC
      and GL) showed optimum physicochemical properties; however, accelerated stability
      study showed considerable differences. GL-1 was appreciably stable for over 6
      months at 4  degrees C. Corresponding gels (PCG-1 and GLG-1) showed C max values
      at 4.98 and 7.32 MUg/mL along with the Tmax values at 4 and 8 hours,
      respectively. GLG-1 inhibited edema production by 90.81% in 6 hours. Discussion.
      PC liposomes are unstable at higher temperature and upon longer storage. The
      formulation with higher lipid content (GL-1) showed good drug retention after 24
      hours and appreciable stability both at higher temperature and for longer
      duration. Guggul lipid being a planar molecule might be stacked in vesicle wall
      with cholesterol. CONCLUSION: The composition of the nanovesicle played an
      important role in stability and drug permeation. Guggul lipid is suitable for
      producing stable vesicles.

PMID- 24672329
TI  - Effects of water models on binding affinity: evidence from all-atom simulation of
      binding of tamiflu to A/H5N1 neuraminidase.
AB  - The influence of water models SPC, SPC/E, TIP3P, and TIP4P on ligand binding
      affinity is examined by calculating the binding free energy DeltaG(bind) of
      oseltamivir carboxylate (Tamiflu) to the wild type of glycoprotein neuraminidase
      from the pandemic A/H5N1 virus. DeltaG(bind) is estimated by the Molecular
      Mechanic-Poisson Boltzmann Surface Area method and all-atom simulations with
      different combinations of these aqueous models and four force fields AMBER99SB,
      CHARMM27, GROMOS96 43a1, and OPLS-AA/L. It is shown that there is no correlation
      between the binding free energy and the water density in the binding pocket in
      CHARMM. However, for three remaining force fields DeltaG(bind) decays with
      increase of water density. SPC/E provides the lowest binding free energy for any
      force field, while the water effect is the most pronounced in CHARMM. In
      agreement with the popular GROMACS recommendation, the binding score obtained by
      combinations of AMBER-TIP3P, OPLS-TIP4P, and GROMOS-SPC is the most relevant to
      the experiments. For wild-type neuraminidase we have found that SPC is more
      suitable for CHARMM than TIP3P recommended by GROMACS for studying ligand
      binding. However, our study for three of its mutants reveals that TIP3P is
      presumably the best choice for CHARMM.

PMID- 24672330
TI  - A multipopulation coevolutionary strategy for multiobjective immune algorithm.
AB  - How to maintain the population diversity is an important issue in designing a
      multiobjective evolutionary algorithm. This paper presents an enhanced
      nondominated neighbor-based immune algorithm in which a multipopulation
      coevolutionary strategy is introduced for improving the population diversity. In
      the proposed algorithm, subpopulations evolve independently; thus the unique
      characteristics of each subpopulation can be effectively maintained, and the
      diversity of the entire population is effectively increased. Besides, the dynamic
      information of multiple subpopulations is obtained with the help of the designed
      cooperation operator which reflects a mutually beneficial relationship among
      subpopulations. Subpopulations gain the opportunity to exchange information,
      thereby expanding the search range of the entire population. Subpopulations make
      use of the reference experience from each other, thereby improving the efficiency
      of evolutionary search. Compared with several state-of-the-art multiobjective
      evolutionary algorithms on well-known and frequently used multiobjective and many
      objective problems, the proposed algorithm achieves comparable results in terms
      of convergence, diversity metrics, and running time on most test problems. 

PMID- 24672332
TI  - Analysis of rainfall infiltration law in unsaturated soil slope.
AB  - In the study of unsaturated soil slope stability under rainfall infiltration, it
      is worth continuing to explore how much rainfall infiltrates into the slope in a
      rain process, and the amount of rainfall infiltrating into slope is the important
      factor influencing the stability. Therefore, rainfall infiltration capacity is an
      important issue of unsaturated seepage analysis for slope. On the basis of
      previous studies, rainfall infiltration law of unsaturated soil slope is
      analyzed. Considering the characteristics of slope and rainfall, the key factors
      affecting rainfall infiltration of slope, including hydraulic properties, water
      storage capacity (thetas - thetar), soil types, rainfall intensities, and
      antecedent and subsequent infiltration rates on unsaturated soil slope, are
      discussed by using theory analysis and numerical simulation technology. Based on
      critical factors changing, this paper presents three calculation models of
      rainfall infiltrability for unsaturated slope, including (1) infiltration model
      considering rainfall intensity; (2) effective rainfall model considering
      antecedent rainfall; (3) infiltration model considering comprehensive factors.
      Based on the technology of system response, the relationship of rainfall and
      infiltration is described, and the prototype of regression model of rainfall
      infiltration is given, in order to determine the amount of rain penetration
      during a rain process.

PMID- 24672331
TI  - Atorvastatin combining with probucol: a new way to reduce serum uric acid level
      during perioperative period of interventional procedure.
AB  - Uric acid has ever been considered as one of contrast induced acute kidney
      injury's risk factors. Atorvastatin and probucol can both improve contrast
      induced acute kidney injury separately. This prospective study is to assess their
      effect on reducing serum uric acid level and contrast induced acute kidney injury
      during perioperative period of interventional procedure. On the basis of
      different doses of atorvastatin and probucol, 208 cases admitted for coronary
      angiography or percutaneous coronary intervention were randomly classified into
      standard combined group (S-C group), intensive combined group (I-C group), and
      intensive atorvastatin group (I-A group). Patients' blood urea nitrogen, serum
      creatinine, and serum uric acid were measured and estimated glomerular filtration
      rate was evaluated 24 hours before and after the procedure. After procedure,
      blood urea nitrogen in all the three groups decreased; Scr of S-C group and I-A
      group increased significantly, while estimated glomerular filtration decreased in
      the S-C group (P < 0.05); serum uric acid in S-C group and I-C group decreased
      significantly (P < 0.05). Combination treatment of atorvastatin and probucol
      before intervention could reduce perioperative serum uric acid level; meanwhile,
      the intensive combined treatment can improve the contrast induced acute kidney
      injury. The result was the same for hypertensive patients. 

PMID- 24672333
TI  - Translational dielectric friction on a chain of charged spheres.
AB  - We have proved in details that the dielectric friction remains the principal
      frictional effect for a stretched polyion modeled as a chain of charged spheres,
      whereas, in the case of Manning's model (infinite thread with a continuous
      distribution of charge), this friction effect is nonexistent. According to this
      chain model, it is therefore possible to detect by conductivity measurements any
      transition from a coiled configuration (ellipsoidal model) to a stretched
      configuration during dilution process. We have also underlined the important
      interdependence between the dielectric friction and the ionic condensation of the
      counterions, in order to distinguish between the Ostwald regime and the Manning
      regime for which the degree of condensation is practically constant in a large
      range of concentrations. 

PMID- 24672334
TI  - Optimal immobilization of beta-galactosidase onto kappa-carrageenan gel beads
      using response surface methodology and its applications.
AB  - beta-Galactosidase (beta-gal) was immobilized by covalent binding on novel kappa
      carrageenan gel beads activated by two-step method; the gel beads were soaked in
      polyethyleneimine followed by glutaraldehyde. 2(2) full-factorial central
      composite experiment designs were employed to optimize the conditions for the
      maximum enzyme loading efficiency. 11.443 U of enzyme/g gel beads was achieved by
      soaking 40 units of enzyme with the gel beads for eight hours. Immobilization
      process increased the pH from 4.5 to 5.5 and operational temperature from 50 to
      55  degrees C compared to the free enzyme. The apparent K(m) after immobilization
      was 61.6 mM compared to 22.9 mM for free enzyme. Maximum velocity Vmax was 131.2
      MU mol . min(-1) while it was 177.1 MU mol . min(-1) for free enzyme. The full
      conversion experiment showed that the immobilized enzyme form is active as that
      of the free enzyme as both of them reached their maximum 100% relative hydrolysis
      at 4 h. The reusability test proved the durability of the kappa-carrageenan beads
      loaded with beta -galactosidase for 20 cycles with retention of 60% of the
      immobilized enzyme activity to be more convenient for industrial uses.

PMID- 24672335
TI  - Semi-online scheduling on two machines with GoS levels and partial information of
      processing time.
AB  - This paper investigates semi-online scheduling problems on two parallel machines
      under a grade of service (GoS) provision subject to minimize the makespan. We
      consider three different semi-online versions with knowing the total processing
      time of the jobs with higher GoS level, knowing the total processing time of the
      jobs with lower GoS level, or knowing both in advance. Respectively, for the
      three semi-online versions, we develop algorithms with competitive ratios of 3/2,
      20/13, and 4/3 which are shown to be optimal. 

PMID- 24672336
TI  - Numerical analysis of the relationship between nasal structure and its function.
AB  - The functions of the nasal cavity are closely related to its structure. In this
      study the three-dimensional finite element models were established based on the
      clinical data of twenty-four volunteers to study the influence of nasal structure
      on nasal functions of heating the inhaled airflow. Numerical simulations mainly
      concerning the airflow distribution and the airflow temperature are performed.
      The character of airflow heating process in these models is gained from the
      simulation results of these nasal cavities. The parameters describing the
      geometry of nasal cavity, such as the surface area of nasal airway and the volume
      of nasal cavity, are considered to be related to the nasal function of heating
      the inhaled airflow. The approximate function describing the relationship between
      the geometric parameters of the nasal airway and the nasal functions is gotten.
      This study can provide a numerical platform for studying some clinical problems
      and will contribute to the further research on the relationship between nasal
      structure and nasal functions. 

PMID- 24672337
TI  - Optimization (central composite design) and validation of HPLC method for
      investigation of emtricitabine loaded poly(lactic-co-glycolic acid)
      nanoparticles: in vitro drug release and in vivo pharmacokinetic studies.
AB  - The objective of the current study is to develop nanoparticles (NPs) drug
      delivery system of emtricitabine solely using poly(lactic-co-glycolic acid)
      (PLGA) and evaluate its in vitro and in vivo release performance by
      systematically optimized HPLC method using Formulation by Design (FbD). NPs were
      evaluated for in vitro release and in vivo absorption study. The desired
      chromatographic separation was achieved on a Phenomenex C18 (250 mm * 4.6 mm
      I.D., 5 MUm) column, under isocratic conditions using UV detection at 280 nm. The
      optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen
      phosphate buffer (pH 6.8), methanol, and 2% acetonitrile in a ratio of (83 : 15 :
      2, v/v/v) at a flow rate of 1 mL/min. The linear regression analysis for the
      calibration curves showed a good linear correlation over the concentration range
      0.040-2.0 MUg/mL, with retention time of 4.39 min. An average encapsulation
      efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order
      release and about 95% drug being released within 15 days in PBS (pH 7.4). In
      conclusion, the proposed optimized method was successfully applied for the
      determination of in vitro and in vivo release studies of emtricitabine NPs.

PMID- 24672338
TI  - Representative elementary length to measure soil mass attenuation coefficient.
AB  - With increasing demand for better yield in agricultural areas, soil physical
      property representative measurements are more and more essential. Nuclear
      techniques such as computerized tomography (CT) and gamma-ray attenuation (GAT)
      have been widely employed with this purpose. The soil mass attenuation
      coefficient (MU(s)) is an important parameter for CT and GAT analysis. When
      experimentally determined (MU(es)), the use of suitable sized samples enable to
      evaluate it precisely, as well as to reduce measurement time and costs. This
      study investigated the representative elementary length (REL) of sandy and clayey
      soils for MU(es) measurements. Two radioactive sources were employed ((241)Am and
      (137)Cs), three collimators (2-4 mm diameters), and 14 thickness (x) samples (2
      15 cm). Results indicated ideal thickness intervals of 12-15 and 2-4 cm for the
      sources (137)Cs and (241)Am, respectively. The application of such results in
      representative elementary area (REA) evaluations in clayey soil clods via CT
      indicated that MU(es) average values obtained for x > 4 cm and source (241)Am
      might induce to the use of samples which are not large enough for soil bulk
      density evaluations (rho(s)). As a consequence, rho(s) might be under- or
      overestimated, generating inaccurate conclusions about the physical quality of
      the soil under study.

PMID- 24672339
TI  - Analgesic, anti-inflammatory, and GC-MS studies on Castanospermum australe A.
      Cunn. & C. Fraser ex Hook.
AB  - The present study was aimed to evaluate the analgesic and anti-inflammatory
      properties of Castanospermum australe and to profile phytochemicals by GC-MS. The
      ethanolic extracts were prepared by successive solvent extraction using Soxhlet
      apparatus. The analgesic activity was analyzed by hot plate method and acetic
      acid-induced writhing test whereas anti-inflammatory study was done by
      carrageenan induced paw oedema model. The acute toxicity study revealed that
      ethanol extracts of leaf and bark of C. australe were safe even at a higher dose
      of 2000 mg/kg whereas ethanol extract of seed was toxic at the same dose. In both
      hot plate method (5.85 s) and acetic acid-induced writhing test (57%), the leaf
      ethanol extract exhibited significant analgesic activity (P < 0.001) at a dose of
      400 mg/kg. The anti-inflammatory activity of leaf extract was exhibited by the
      reduction in paw linear diameter by 64.76% at 400 mg/kg in carrageenan induced
      paw oedema. The GC-MS analysis of the ethanol extract of leaf revealed sixteen
      major compounds of which 1,7-dimethyl-4,10-dioxa-1,7-diazacyclododecane, (+)-N
      methylephedrine, and permethylspermine were found to be pharmaceutically and the
      most important. These findings justify that C. australe can be a valuable natural
      analgesic and anti-inflammatory source which seemed to provide potential
      phytotherapeutics against various ailments.

PMID- 24672340
TI  - Stochastic theta-methods for a class of jump-diffusion stochastic pantograph
      equations with random magnitude.
AB  - This paper is concerned with the convergence of stochastic theta-methods for
      stochastic pantograph equations with Poisson-driven jumps of random magnitude.
      The strong order of the convergence of the numerical method is given, and the
      convergence of the numerical method is obtained. Some earlier results are
      generalized and improved. 

PMID- 24672341
TI  - Numerical study on influence of cross flow on rewetting of AHWR fuel bundle.
AB  - Numerical study on AHWR fuel bundle has been carried out to assess influence of
      circumferential and cross flow rewetting on the conduction heat transfer. The
      AHWR fuel bundle quenching under accident condition is designed primarily with
      radial jets at several axial locations. A 3D (r, theta, z) transient conduction
      fuel pin model has been developed to carry out the study with a finite difference
      method (FDM) technique with alternating direction implicit (ADI) scheme. The
      single pin has been considered to study effect of circumferential conduction and
      multipins have been considered to study the influence of cross flow. Both
      analyses are carried out with the same fluid temperature and heat transfer
      coefficients as boundary conditions. It has been found from the analyses that,
      for radial jet, the circumferential conduction is significant and due to
      influence of overall cross flow the reductions in fuel temperature in the same
      quench plane in different rings are different with same initial surface
      temperature. Influence of cross flow on rewetting is found to be very
      significant. Outer fuel pins rewetting time is higher than inner. 

PMID- 24672342
TI  - Organic solvent tolerant lipases and applications.
AB  - Lipases are a group of enzymes naturally endowed with the property of performing
      reactions in aqueous as well as organic solvents. The esterification reactions
      using lipase(s) could be performed in water-restricted organic media as organic
      solvent(s) not only improve(s) the solubility of substrate and reactant in
      reaction mixture but also permit(s) the reaction in the reverse direction, and
      often it is easy to recover the product in organic phase in two-phase equilibrium
      systems. The use of organic solvent tolerant lipase in organic media has
      exhibited many advantages: increased activity and stability, regiospecificity and
      stereoselectivity, higher solubility of substrate, ease of products recovery, and
      ability to shift the reaction equilibrium toward synthetic direction. Therefore
      the search for organic solvent tolerant enzymes has been an extensive area of
      research. A variety of fatty acid esters are now being produced commercially
      using immobilized lipase in nonaqueous solvents. This review describes the
      organic tolerance and industrial application of lipases. The main emphasis is to
      study the nature of organic solvent tolerant lipases. Also, the potential
      industrial applications that make lipases the biocatalysts of choice for the
      present and future have been presented. 

PMID- 24672343
TI  - Behavior of nonplastic silty soils under cyclic loading.
AB  - The engineering behavior of nonplastic silts is more difficult to characterize
      than is the behavior of clay or sand. Especially, behavior of silty soils is
      important in view of the seismicity of several regions of alluvial deposits in
      the world, such as the United States, China, and Turkey. In several hazards
      substantial ground deformation, reduced bearing capacity, and liquefaction of
      silty soils have been attributed to excess pore pressure generation during
      dynamic loading. In this paper, an experimental study of the pore water pressure
      generation of silty soils was conducted by cyclic triaxial tests on samples of
      reconstituted soils by the slurry deposition method. In all tests silty samples
      which have different clay percentages were studied under different cyclic stress
      ratios. The results have showed that in soils having clay content equal to and
      less than 10%, the excess pore pressure ratio buildup was quicker with an
      increase in different cyclic stress ratios. When fine and clay content increases,
      excess pore water pressure decreases constant cyclic stress ratio in nonplastic
      silty soils. In addition, the applicability of the used criteria for the
      assessment of liquefaction susceptibility of fine grained soils is examined using
      laboratory test results. 

PMID- 24672344
TI  - Epidemiology of orthopedic fractures and other injuries among inpatients admitted
      due to traffic accidents: a 10-year nationwide survey in Taiwan.
AB  - To investigate the major injury patterns associated with traffic accidents and
      evaluate the risk factors of the main injury, a survey of Taiwan's national
      insurance admission data between 2002 and 2011 was performed. The incidence of
      traffic-accidents-related hospitalization was between 9.17% and 11.54% and the
      average mortality rate of the inpatients admitted due to traffic accidents was
      0.68%. Of all inpatients due to road traffic accidents in Taiwan, orthopedic
      fractures were the most common injuries that accounted for 29.36% of them. There
      were a total of 391,197 cases of three orthopedic fracture groups that were
      divided into (1) fracture of upper limb, (2) fracture of lower limb, and (3)
      fracture of spine and trunk. An increase in national medical cost used for
      inpatients with orthopedic fractures was noted and ranged from US$ 45.6 million
      to US$ 86 million annually. These orthopedic fracture patterns were frequently
      associated with other injuries especially head injuries (ranged from 14% to 26%).
      A significant relation to male gender, older age, low income, and admission to
      high-level hospital to the observed fracture patterns was observed. 

PMID- 24672345
TI  - The relationship analysis between water injection and microfacies of SHA1
      reservoir of Liao He Basin, China.
AB  - SHA1 is the representative reservoir in Liao He Basin. Through the introduction
      of curvature displayed on the gray scale, we determine the substructure and
      fractures. Geostatistical inversion method is used to help study the porosity of
      reservoir. The relationship between interval transit times and resistivity among
      mudstone and sandstone, before and after water injection, is analyzed. The
      relationship between porosity and permeability and the relationship between
      porosity and impedance from core analysis were studied. Through the whole
      information above, we divide the microfacies of SHA1 reservoir to distributary
      channel, mouth bar, the leading edge thin sand, and prodelta mud. The water
      injections in different microfacies are studied. The distributary channel should
      be used by large distant injection wells or smaller injection pressure injection.
      The smaller distant injection wells or large injection pressure should be used in
      the mouth bar. The arrangement of well injection need consider the different
      sedimentary microfacies. 

PMID- 24672346
TI  - Biodegradation of spilled diesel fuel in agricultural soil: effect of humates,
      zeolite, and bioaugmentation.
AB  - Possible enhancement of biodegradation of petroleum hydrocarbons in agricultural
      soil after tank truck accident (~5000 mg/kg dry soil initial concentration) by
      bioaugmentation of diesel degrading Pseudomonas fluorescens strain and addition
      of abiotic additives (humates, zeolite) was studied in a 9-month pot experiment.
      The biodegradation process was followed by means of analytical parameters
      (hydrocarbon index expressed as content of C10-C40 aliphatic hydrocarbons, ratio
      pristane/C17, and total organic carbon content) and characterization of soil
      microbial community (content of phospholipid fatty acids (PLFA) as an indicator
      of living microbial biomass, respiration, and dehydrogenase activity). The
      concentration of petroleum hydrocarbons (C10-C40) was successfully reduced by
      ~60% in all 15 experiment variants. The bioaugmentation resulted in faster
      hydrocarbon elimination. On the contrary, the addition of humates and zeolite
      caused only a negligible increase in the degradation rate. These factors,
      however, affected significantly the amount of PLFA. The humates caused
      significantly faster increase of the total PLFA suggesting improvement of the
      soil microenvironment. Zeolite caused significantly slower increase of the total
      PLFA; nevertheless it aided in homogenization of the soil. Comparison of
      microbial activities and total PLFA revealed that only a small fraction of
      autochthonous microbes took part in the biodegradation which confirms that
      bioaugmentation was the most important treatment.

PMID- 24672347
TI  - Body size mediated coexistence in swans.
AB  - Differences in body sizes may create a trade-off between foraging efficiency
      (foraging gains/costs) and access to resources. Such a trade-off provides a
      potential mechanism for ecologically similar species to coexist on one resource.
      We explored this hypothesis for tundra (Cygnus columbianus) and trumpeter swans
      (Cygnus buccinator), a federally protected species, feeding solely on sago
      pondweed (Stuckenia pectinata) tubers during fall staging and wintering in
      northern Utah. Foraging efficiency was higher for tundra swans because this
      species experienced lower foraging and metabolic costs relative to foraging
      gains; however, trumpeter swans (a) had longer necks and therefore had access to
      exclusive resources buried deep in wetland sediments and (b) were more aggressive
      and could therefore displace tundra swans from lucrative foraging locations. We
      conclude that body size differentiation is an important feature of coexistence
      among ecologically similar species feeding on one resource. In situations where
      resources are limiting and competition for resources is strong, conservation
      managers will need to consider the trade-off between foraging efficiency and
      access to resources to ensure ecologically similar species can coexist on a
      shared resource. 

PMID- 24672349
TI  - High efficiency direct shoot organogenesis from leaf segments of Aerva lanata
      (L.) Juss. ex Schult by using thidiazuron.
AB  - An efficient protocol for direct shoot organogenesis has been developed for the
      medicinal plant Aerva lanata (L.) Juss. ex Schult. Regeneration was achieved from
      leaf segments of 20 days old in vitro plantlets raised on Murashige and Skoog
      (MS) medium containing 0.25-2.0 mg L(-1) thiadiazuron (TDZ), 3% sucrose, and 0.8%
      agar. After 21 days of culture incubation, maximum number of shoot organogenesis
      (23.6 +/- 0.16) was obtained on medium containing 1.0 mg L(-1) TDZ. The shoots
      were able to produce in vitro flowers on medium containing 1.0 mg L(-1) TDZ in
      combination with 0.25-0.5 mg L(-1)  alpha-naphthaleneacetic acid (NAA).
      Histological observation showed that the epidermal cells of the leaf explants
      exhibited continuous cell division led to formation of numerous dome shaped
      meristematic protrusions and subsequently developed into adventitious shoots.
      Upon transfer of shootlets to half strength MS medium containing 1.0 mg L(-1)
      indole-3-butyric acid (IBA), around 86% of the regenerated shoots formed roots
      and plantlets. Rooted plants were hardened and successfully established in the
      soil at the survival rate of 92%. The regeneration protocol developed in this
      study provides an important method of micropropagation of this plant.
      Furthermore, this protocol may be used for a large scale production of its
      medicinally active compounds and genetic transformations for further improvement.

PMID- 24672348
TI  - A perspective review on numerical simulations of hemodynamics in aortic
      dissection.
AB  - Aortic dissection, characterized by separation of the layers of the aortic wall,
      poses a significant challenge for clinicians. While type A aortic dissection
      patients are normally managed using surgical treatment, optimal treatment
      strategy for type B aortic dissection remains controversial and requires further
      evaluation. Although aortic diameter measured by CT angiography has been
      clinically used as a guideline to predict dilation in aortic dissection,
      hemodynamic parameters (e.g., pressure and wall shear stress), geometrical
      factors, and composition of the aorta wall are known to substantially affect
      disease progression. Due to the limitations of cardiac imaging modalities,
      numerical simulations have been widely used for the prediction of disease
      progression and therapeutic outcomes, by providing detailed insights into the
      hemodynamics. This paper presents a comprehensive review of the existing
      numerical models developed to investigate reasons behind tear initiation and
      progression, as well as the effectiveness of various treatment strategies,
      particularly the stent graft treatment. 

PMID- 24672350
TI  - Sonographic wrist measurements and detection of anatomical features in carpal
      tunnel syndrome.
AB  - INTRODUCTION: This study compares anatomical findings at wrist level in patients
      with known carpal tunnel syndrome (CTS) and controls by ultrasonography (US).
      MATERIAL AND METHODS: Wrist-US investigations of 28 consecutive patients with 38
      diagnosed, idiopathic CTS were compared to 49 healthy volunteers without history
      of CTS. Internal wrists dimensions, the presence of flexor muscle bellies in the
      carpal tunnel, and cross-sectional area of the median nerve were analyzed. The
      findings were correlated to gender, age, and BMI. RESULTS: US demonstrated a
      square internal carpal tunnel configuration in CTS patients compared to controls
      (P < 0.001). Patients with CTS showed a trend towards the presence of flexor
      muscles bellies in the carpal tunnel (odds ratio 1.77, 95% CI 0.337-8.33). CTS
      was present in women with higher BMI (P = 0.015). CONCLUSION: US allowed
      detection of specific anatomical features at wrist level in CTS patients. This
      observation may enable--following confirmation in larger prospective studies-
      risk evaluation for CTS development.

PMID- 24672351
TI  - An innovative time-cost-quality tradeoff modeling of building construction
      project based on resource allocation.
AB  - The time, quality, and cost are three important but contradictive objectives in a
      building construction project. It is a tough challenge for project managers to
      optimize them since they are different parameters. This paper presents a time
      cost-quality optimization model that enables managers to optimize
      multiobjectives. The model is from the project breakdown structure method where
      task resources in a construction project are divided into a series of activities
      and further into construction labors, materials, equipment, and administration.
      The resources utilized in a construction activity would eventually determine its
      construction time, cost, and quality, and a complex time-cost-quality trade-off
      model is finally generated based on correlations between construction activities.
      A genetic algorithm tool is applied in the model to solve the comprehensive
      nonlinear time-cost-quality problems. Building of a three-storey house is an
      example to illustrate the implementation of the model, demonstrate its advantages
      in optimizing trade-off of construction time, cost, and quality, and help make a
      winning decision in construction practices. The computational time-cost-quality
      curves in visual graphics from the case study prove traditional cost-time
      assumptions reasonable and also prove this time-cost-quality trade-off model
      sophisticated. 

PMID- 24672352
TI  - PPF dependent fixed point results for triangular alphac-admissible mappings.
AB  - We introduce the concept of triangular alphac-admissible mappings (pair of
      mappings) with respect to etac nonself-mappings and establish the existence of
      PPF dependent fixed (coincidence) point theorems for contraction mappings
      involving triangular alphac-admissible mappings (pair of mappings) with respect
      to etac nonself-mappings in Razumikhin class. Several interesting consequences of
      our theorems are also given.

PMID- 24672353
TI  - Using the satisfaction with life scale in people with Parkinson's disease: a
      validation study in different European countries.
AB  - BACKGROUND: Overall, people with chronic illnesses have lower life satisfaction
      compared to nonclinical populations. The objective of this international study
      was to examine the psychometric properties of the Satisfaction with Life Scale
      (SWLS) in patients with Parkinson's disease (PD). METHODS: PD patients (n = 350)
      were recruited and interviewed at different specialized services in the United
      Kingdom, Spain, Czech Republic, Italy, and The Netherlands. A questionnaire set
      including a measure of life satisfaction, quality of life (QoL), self-reported
      health and disability status, and sociodemographic information was used.
      Acceptability, reliability, and validity were examined. RESULTS: The internal
      consistency was good ( alpha = 0.81). The scale structure was satisfactory
      (comparative fit index = 0.99; root mean square error of approximation = 0.08).
      The SWLS was able to discriminate between healthy and unhealthy, disabled and
      nondisabled, and those perceiving a more severe impact of the disability on their
      lives. Concurrent validity using multiple linear regression models confirmed
      associations between SWLS and QoL and age. CONCLUSIONS: This study is the first
      to report on the use of the SWLS in PD patients in different European countries.
      It is a useful tool in assessing satisfaction with life in PD patients through
      the continuum of care.

PMID- 24672354
TI  - Synthesis of cobalt oxides thin films fractal structures by laser chemical vapor
      deposition.
AB  - Thin films of cobalt oxides (CoO and Co3O4) fractal structures have been
      synthesized by using laser chemical vapor deposition at room temperature and
      atmospheric pressure. Various factors which affect the density and
      crystallization of cobalt oxides fractal shapes have been examined. We show that
      the fractal structures can be described by diffusion-limited aggregation model
      and discuss a new possibility to control the fractal structures. 

PMID- 24672355
TI  - Emerging stent and balloon technologies in the femoropopliteal arteries.
AB  - Endovascular procedures for the management of the superficial femoral (SFA) and
      popliteal artery disease are increasingly common. Over the past decade, several
      stent technologies have been established which may offer new options for improved
      clinical outcomes. This paper reviews the current evidence for SFA and popliteal
      artery angioplasty and stenting, with a focus on randomized trials and registries
      of nitinol self-expanding stents, drug-eluting stents, dug-coated balloons, and
      covered stent-grafts. We also highlight the limitations of the currently
      available data and the future routes in peripheral arterial disease (PAD) stent
      and balloon technology. 

PMID- 24672356
TI  - Study on noise prediction model and control schemes for substation.
AB  - With the government's emphasis on environmental issues of power transmission and
      transformation project, noise pollution has become a prominent problem now. The
      noise from the working transformer, reactor, and other electrical equipment in
      the substation will bring negative effect to the ambient environment. This paper
      focuses on using acoustic software for the simulation and calculation method to
      control substation noise. According to the characteristics of the substation
      noise and the techniques of noise reduction, a substation's acoustic field model
      was established with the SoundPLAN software to predict the scope of substation
      noise. On this basis, 4 reasonable noise control schemes were advanced to provide
      some helpful references for noise control during the new substation's design and
      construction process. And the feasibility and application effect of these control
      schemes can be verified by using the method of simulation modeling. The
      simulation results show that the substation always has the problem of excessive
      noise at boundary under the conventional measures. The excess noise can be
      efficiently reduced by taking the corresponding noise reduction methods. 

PMID- 24672357
TI  - The polymorphism of the ACE gene affects left ventricular hypertrophy and causes
      disturbances in left ventricular systolic/diastolic function in patients with
      autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most
      frequently occurring autosomal diseases inherited in the dominant manner. Due to
      this, lesions in the cardiovascular system of ADPKD patients have caught the
      attention of clinical investigators worldwide. The aim of the study was to
      analyse cardiovascular complications in ADPKD patients with a focus on left
      ventricular hypertrophy (LVH) and selected components of its systolic/diastolic
      function based on echocardiography. The study was conducted on 55 patients with
      ADPKD (24 males, 31 females), subdivided into three groups according to the stage
      of chronic kidney disease (CKD). The patient group with ADPKD and ESRD (group C)
      manifested an increased incidence of the D allele as compared to group A and
      group B (chi(2) = 4.217, P = 0.04). In all ADPKD patients with the DD genotype,
      left ventricular mass (LVM), posterior wall thickness (PWT), and interventricular
      septal thickness (IVS) were significantly higher compared to patients possessing
      the II and ID genotypes (P < 0.02, P < 0.003, and P < 0.009, resp.). The DD
      genotype exists more frequently in ADPKD patients with ESRD and is associated
      with a higher occurrence of LVH and disturbances in systolic-diastolic function
      when compared to ADPKD ESRD patients with the II and ID genotypes.

PMID- 24672358
TI  - Suicide attempts in Malaysia from the year 1969 to 2011.
AB  - The aim of this paper is to review the literature on suicide attempts in
      Malaysia. PsycINFO, PubMed, and Medline databases from 1845 to 2012 and detailed
      manual search of local official reports from the Ministry of Health and the
      Malaysian Psychiatric Association and unpublished dissertations from 3 local
      universities providing postgraduate psychiatric training were included in the
      current review. A total of 38 studies on suicide attempts in Malaysia were found
      and reviewed. Twenty-seven (76%) of the studies on suicide attempts were
      descriptive studies looking at sociodemographic data, psychiatric illnesses, and
      methods and reasons for suicide attempts. No study has been conducted on
      treatment and interventions for suicide attempts and the impact of culture was
      rarely considered. The review showed that in order for researchers, clinicians,
      and public health policy makers to obtain a better understanding of suicide
      attempts in Malaysia, more systematic and empirically stringent methodologies and
      research frameworks need to be used. 

PMID- 24672359
TI  - Locating damage using integrated global-local approach with wireless sensing
      system and single-chip impedance measurement device.
AB  - This study developed an integrated global-local approach for locating damage on
      building structures. A damage detection approach with a novel embedded frequency
      response function damage index (NEFDI) was proposed and embedded in the
      Imote2.NET-based wireless structural health monitoring (SHM) system to locate
      global damage. Local damage is then identified using an electromechanical
      impedance- (EMI-) based damage detection method. The electromechanical impedance
      was measured using a single-chip impedance measurement device which has the
      advantages of small size, low cost, and portability. The feasibility of the
      proposed damage detection scheme was studied with reference to a numerical
      example of a six-storey shear plane frame structure and a small-scale
      experimental steel frame. Numerical and experimental analysis using the
      integrated global-local SHM approach reveals that, after NEFDI indicates the
      approximate location of a damaged area, the EMI-based damage detection approach
      can then identify the detailed damage location in the structure of the building. 

PMID- 24672360
TI  - DSMC simulation and experimental validation of shock interaction in hypersonic
      low density flow.
AB  - Direct simulation Monte Carlo (DSMC) of shock interaction in hypersonic low
      density flow is developed. Three collision molecular models, including hard
      sphere (HS), variable hard sphere (VHS), and variable soft sphere (VSS), are
      employed in the DSMC study. The simulations of double-cone and Edney's type IV
      hypersonic shock interactions in low density flow are performed. Comparisons
      between DSMC and experimental data are conducted. Investigation of the double
      cone hypersonic flow shows that three collision molecular models can predict the
      trend of pressure coefficient and the Stanton number. HS model shows the best
      agreement between DSMC simulation and experiment among three collision molecular
      models. Also, it shows that the agreement between DSMC and experiment is
      generally good for HS and VHS models in Edney's type IV shock interaction.
      However, it fails in the VSS model. Both double-cone and Edney's type IV shock
      interaction simulations show that the DSMC errors depend on the Knudsen number
      and the models employed for intermolecular interaction. With the increase in the
      Knudsen number, the DSMC error is decreased. The error is the smallest in HS
      compared with those in the VHS and VSS models. When the Knudsen number is in the
      level of 10(-4), the DSMC errors, for pressure coefficient, the Stanton number,
      and the scale of interaction region, are controlled within 10%. 

PMID- 24672361
TI  - Designing a Facebook interface for senior users.
AB  - The adoption of social networks by older adults has increased in recent years.
      However, many still cannot make use of social networks as these are simply not
      adapted to them. Through a series of direct observations, interviews, and focus
      groups, we identified recommendations for the design of social networks targeting
      seniors. Based on these, we developed a prototype for tablet devices, supporting
      sharing and viewing Facebook content. We then conducted a user study comparing
      our prototype with Facebook's native mobile application. We have found that
      Facebook's native application does not meet senior users concerns, like privacy
      and family focus, while our prototype, designed in accordance with the collected
      recommendations, supported relevant use cases in a usable and accessible manner. 

PMID- 24672363
TI  - New graduate nurses' clinical competence, clinical stress, and intention to
      leave: a longitudinal study in Taiwan.
AB  - This longitudinal research study aimed to develop a pregraduation clinical
      training program for nursing students before graduation and evaluate its effect
      on students' self-perceived clinical competence, clinical stress, and intention
      to leave current job. A sample of 198 students returned the questionnaires before
      and after the program. They were followed up at 3, 6, and 12 months after
      graduation. Results showed that posttest clinical competence was significantly
      higher than pretest competence, positively related to clinical competence at 3
      and 12 months, and negatively related to clinical stress at 3 months. The
      clinical competence at 3 months was positively related to clinical competence at
      6 and 12 months, and clinical competence at 6 months was related to intention to
      leave at 12 months. Intention to leave at 6 months was positively related to
      intention to leave at 3 and 12 months. Clinical stress at 3 months was positively
      related to clinical stress at 6 and 12 months, but not related to intention to
      leave at any time points. The training program improved students' clinical
      competence. The stressful time that was correlated with new graduate nurses'
      intention to leave their job was between the sixth and twelfth months after
      employment. 

PMID- 24672364
TI  - Estimating the pollution risk of cadmium in soil using a composite soil
      environmental quality standard.
AB  - Estimating standard-exceeding probabilities of toxic metals in soil is crucial
      for environmental evaluation. Because soil pH and land use types have strong
      effects on the bioavailability of trace metals in soil, they were taken into
      account by some environmental protection agencies in making composite soil
      environmental quality standards (SEQSs) that contain multiple metal thresholds
      under different pH and land use conditions. This study proposed a method for
      estimating the standard-exceeding probability map of soil cadmium using a
      composite SEQS. The spatial variability and uncertainty of soil pH and site
      specific land use type were incorporated through simulated realizations by
      sequential Gaussian simulation. A case study was conducted using a sample data
      set from a 150 km(2) area in Wuhan City and the composite SEQS for cadmium,
      recently set by the State Environmental Protection Administration of China. The
      method may be useful for evaluating the pollution risks of trace metals in soil
      with composite SEQSs.

PMID- 24672366
TI  - Partial rectangular metric spaces and fixed point theorems.
AB  - The purpose of this paper is to introduce the concept of partial rectangular
      metric spaces as a generalization of rectangular metric and partial metric
      spaces. Some properties of partial rectangular metric spaces and some fixed point
      results for quasitype contraction in partial rectangular metric spaces are
      proved. Some examples are given to illustrate the observed results. 

PMID- 24672365
TI  - Technical quality of root fillings performed by undergraduate students: a
      radiographic study.
AB  - AIM: The aim of this study was to evaluate the radiographic technical quality of
      endodontic treatment performed by undergraduate students at the School of
      Dentistry, Faculty of Medicine, University of Novi Sad, Serbia. MATERIALS AND
      METHODS: Electronic records of 220 patients treated by final-year undergraduate
      students during the school year 2011/2012 were examined, and the final sample
      consisted of 212 patients, 322 teeth, and 565 root canals. The criteria for
      overall radiographic adequacy of root canal fillings were defined as the presence
      of adequate length and density and absence of iatrogenic errors (ledge, fractured
      instrument, untreated canal, and apical transportation). Chi-square test was used
      to determine statistical significance between different parameters. RESULTS:
      Adequate root canal fillings were found in 74.22% of the teeth. The percentage of
      root fillings with adequate length and density was 89.73% and 92.6%,
      respectively. Fractured instruments and ledges were present in 16 root canals
      (2.8%), while the presence of missed canal and apical transportation was observed
      in 2 cases, each (0.3%). CONCLUSIONS: Overall, the technical quality of root
      canal fillings performed by undergraduate students was satisfactory.

PMID- 24672367
TI  - Numerical solution of boundary layer MHD flow with viscous dissipation.
AB  - The present paper deals with a steady two-dimensional laminar flow of a viscous
      incompressible electrically conducting fluid over a shrinking sheet in the
      presence of uniform transverse magnetic field with viscous dissipation. Using
      suitable similarity transformations the governing partial differential equations
      are transformed into ordinary differential equations and then solved numerically
      by fourth-order Runge-Kutta method with shooting technique. Results for velocity
      and temperature profiles for different values of the governing parameters have
      been discussed in detail with graphical representation. The numerical evaluation
      of skin friction and Nusselt number are also given in this paper. 

PMID- 24672362
TI  - Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes,
      risk factors, diagnosis, and prognosis.
AB  - Lichen planus (LP) is a chronic inflammatory disorder that most often affects
      middle-aged adults. LP can involve the skin or mucous membranes including the
      oral, vulvovaginal, esophageal, laryngeal, and conjunctival mucosa. It has
      different variants based on the morphology of the lesions and the site of
      involvement. The literature suggests that certain presentations of the disease
      such as esophageal or ophthalmological involvement are underdiagnosed. The burden
      of the disease is higher in some variants including hypertrophic LP and erosive
      oral LP, which may have a more chronic pattern. LP can significantly affect the
      quality of life of patients as well. Drugs or contact allergens can cause
      lichenoid reactions as the main differential diagnosis of LP. LP is a T-cell
      mediated immunologic disease but the responsible antigen remains unidentified. In
      this paper, we review the history, epidemiology, and clinical subtypes of LP. We
      also review the histopathologic aspects of the disease, differential diagnoses,
      immunopathogenesis, and the clinical and genetic correlations. 

PMID- 24672368
TI  - Thermodynamics analysis of refinery sludge gasification in adiabatic updraft
      gasifier.
AB  - Limited information is available about the thermodynamic evaluation for biomass
      gasification process using updraft gasifier. Therefore, to minimize errors, the
      gasification of dry refinery sludge (DRS) is carried out in adiabatic system at
      atmospheric pressure under ambient air conditions. The objectives of this paper
      are to investigate the physical and chemical energy and exergy of product gas at
      different equivalent ratios (ER). It will also be used to determine whether the
      cold gas, exergy, and energy efficiencies of gases may be maximized by using
      secondary air injected to gasification zone under various ratios (0, 0.5, 1, and
      1.5) at optimum ER of 0.195. From the results obtained, it is indicated that the
      chemical energy and exergy of producer gas are magnified by 5 and 10 times higher
      than their corresponding physical values, respectively. The cold gas, energy, and
      exergy efficiencies of DRS gasification are in the ranges of 22.9-55.5%, 43.7
      72.4%, and 42.5-50.4%, respectively. Initially, all 3 efficiencies increase until
      they reach a maximum at the optimum ER of 0.195; thereafter, they decline with
      further increase in ER values. The injection of secondary air to gasification
      zone is also found to increase the cold gas, energy, and exergy efficiencies. A
      ratio of secondary air to primary air of 0.5 is found to be the optimum ratio for
      all 3 efficiencies to reach the maximum values. 

PMID- 24672369
TI  - Comparative study of antioxidant status in androgenic embryos of Aesculus
      hippocastanum and Aesculus flava.
AB  - In vivo (leaves and seed embryos) and in vitro (androgenic embryos) antioxidant
      scavenging activity of Aesculus hippocastanum and Aesculus flava medical plants
      was examined. Here we report antioxidant enzyme activities of superoxide
      dismutase, catalase, guaiacol peroxidase and glutathione peroxidase, reduced
      glutathione quantity, flavonoids, soluble protein contents, quantities of
      malondialdehyde, and (*)OH radical presence in the investigated plant samples.
      Total antioxidant capacity of all the samples of A. hippocastanum and A. flava
      was determined using FRAP, DPPH, and NO(*) radical scavenger capacity. The leaves
      of A. flava collected from the botanical garden exhibited stronger antioxidant
      activity (higher activities of SOD, and higher quantities of GSH, TSH, TPC, and
      scavenging abilities of DPPH and NO(*), and higher FRAP values and lowest
      quantities of (*)OH and MDA) than in vitro obtained cultures. However, the leaves
      of A. flava showed higher antioxidant activity than the leaves of A.
      hippocastanum, and therefore they have a stronger tolerance of oxidative stress.
      Androgenic embryos of both species had low amount of antioxidants due to
      controlled in vitro environmental conditions (T, photoperiod, humidity, nutritive
      factors, and pathogen-free). Our results confirmed that we found optimal in vitro
      conditions for producing androgenic embryos of both Aesculus species. Also, we
      assume that horse chestnut androgenic embryos can be used as an alternative
      source for large-scale aescin production. 

PMID- 24672370
TI  - Development of pulsating twin jets mechanism for mixing flow heat transfer
      analysis.
AB  - Pulsating twin jets mechanism (PTJM) was developed in the present work to study
      the effect of pulsating twin jets mixing region on the enhancement of heat
      transfer. Controllable characteristics twin pulsed jets were the main objective
      of our design. The variable nozzle-nozzle distance was considered to study the
      effect of two jets interaction at the mixing region. Also, the phase change
      between the frequencies of twin jets was taken into account to develop PTJM. All
      of these factors in addition to the ability of producing high velocity pulsed jet
      led to more appropriate design for a comprehensive study of multijet impingement
      heat transfer problems. The performance of PTJM was verified by measuring the
      pulse profile at frequency of 20 Hz, where equal velocity peak of around 64 m/s
      for both jets was obtained. Moreover, the jet velocity profile at different
      pulsation frequencies was tested to verify system performance, so the results
      revealed reasonable velocity profile configuration. Furthermore, the effect of
      pulsation frequency on surface temperature of flat hot plate in the midpoint
      between twin jets was studied experimentally. Noticeable enhancement in heat
      transfer was obtained with the increasing of pulsation frequency.

PMID- 24672371
TI  - Data delivery method based on neighbor nodes' information in a mobile ad hoc
      network.
AB  - This paper proposes a data delivery method based on neighbor nodes' information
      to achieve reliable communication in a mobile ad hoc network (MANET). In a MANET,
      it is difficult to deliver data reliably due to instabilities in network topology
      and wireless network condition which result from node movement. To overcome such
      unstable communication, opportunistic routing and network coding schemes have
      lately attracted considerable attention. Although an existing method that employs
      such schemes, MAC-independent opportunistic routing and encoding (MORE),
      Chachulski et al. (2007), improves the efficiency of data delivery in an unstable
      wireless mesh network, it does not address node movement. To efficiently deliver
      data in a MANET, the method proposed in this paper thus first employs the same
      opportunistic routing and network coding used in MORE and also uses the location
      information and transmission probabilities of neighbor nodes to adapt to
      changeable network topology and wireless network condition. The simulation
      experiments showed that the proposed method can achieve efficient data delivery
      with low network load when the movement speed is relatively slow. 

PMID- 24672372
TI  - Contactless electric igniter for vehicle to lower exhaust emission and fuel
      consumption.
AB  - An electric igniter for engine/hybrid vehicles is presented. The igniter
      comprises a flyback converter, a voltage-stacked capacitor, a PIC-based
      controller, a differential voltage detector, and an ignition coil, of which
      structure is non-contact type. Since the electric igniter adopts a capacitor to
      accumulate energy for engine ignition instead of traditional contacttype
      approach, it enhances the igniting performance of a spark plug effectively. As a
      result, combustion efficiency is promoted, fuel consumption is saved, and exhaust
      emission is reduced. The igniter not only is good for fuel efficiency but also
      can reduce HC and CO emission significantly, which therefore is an
      environmentally friendly product. The control core of the igniter is implemented
      on a single chip, which lowers discrete component count, reduces system volume,
      and increases reliability. In addition, the ignition timing can be programmed so
      that a timing regulator can be removed from the proposed system, simplifying its
      structure. To verify the feasibility and functionality of the igniter, key
      waveforms are measured and real-car experiments are performed as well. 

PMID- 24672373
TI  - Brain monitoring: do we need a hole? An update on invasive and noninvasive brain
      monitoring modalities.
AB  - The ability to measure reliably the changes in the physical and biochemical
      environment after a brain injury is of great value in the prevention, treatment,
      and understanding of the secondary injuries. Three categories of multimodal brain
      monitoring exist: direct signals which are monitored invasively; variables which
      may be monitored noninvasively; and variables describing brain pathophysiology
      which are not monitored directly but are calculated at the bedside by dedicated
      computer software. Intracranial pressure (ICP) monitoring, either as stand-alone
      value or study of a dynamic trend, has become an important diagnostic tool in the
      diagnosis and management of multiple neurological conditions. Attempts have been
      made to measure ICP non-invasively, but this is not a clinical reality yet. There
      is contrasting evidence that monitoring of ICP is associated with better outcome,
      and further RCTs based on management protocol are warranted. Computer bedside
      calculation of "secondary parameters" has shown to be potentially helpful,
      particularly in helping to optimize "CPP-guided therapy." In this paper we
      describe the most popular invasive and non invasive monitoring modalities, with
      great attention to their clinical interpretation based on the current published
      evidence. 

PMID- 24672374
TI  - A neural-network-based approach to white blood cell classification.
AB  - This paper presents a new white blood cell classification system for the
      recognition of five types of white blood cells. We propose a new segmentation
      algorithm for the segmentation of white blood cells from smear images. The core
      idea of the proposed segmentation algorithm is to find a discriminating region of
      white blood cells on the HSI color space. Pixels with color lying in the
      discriminating region described by an ellipsoidal region will be regarded as the
      nucleus and granule of cytoplasm of a white blood cell. Then, through a further
      morphological process, we can segment a white blood cell from a smear image.
      Three kinds of features (i.e., geometrical features, color features, and LDP
      based texture features) are extracted from the segmented cell. These features are
      fed into three different kinds of neural networks to recognize the types of the
      white blood cells. To test the effectiveness of the proposed white blood cell
      classification system, a total of 450 white blood cells images were used. The
      highest overall correct recognition rate could reach 99.11% correct. Simulation
      results showed that the proposed white blood cell classification system was very
      competitive to some existing systems. 

PMID- 24672375
TI  - Coefficient inequalities for a subclass of p-valent analytic functions.
AB  - The aim of this paper is to study the problem of coefficient bounds for a newly
      defined subclass of p-valent analytic functions. Many known results appear as
      special consequences of our work. 

PMID- 24672376
TI  - A robust H.264/AVC video watermarking scheme with drift compensation.
AB  - A robust H.264/AVC video watermarking scheme for copyright protection with self
      adaptive drift compensation is proposed. In our scheme, motion vector residuals
      of macroblocks with the smallest partition size are selected to hide copyright
      information in order to hold visual impact and distortion drift to a minimum.
      Drift compensation is also implemented to reduce the influence of watermark to
      the most extent. Besides, discrete cosine transform (DCT) with energy compact
      property is applied to the motion vector residual group, which can ensure
      robustness against intentional attacks. According to the experimental results,
      this scheme gains excellent imperceptibility and low bit-rate increase. Malicious
      attacks with different quantization parameters (QPs) or motion estimation
      algorithms can be resisted efficiently, with 80% accuracy on average after lossy
      compression. 

PMID- 24672377
TI  - Effect of vertically propagating shear waves on seismic behavior of circular
      tunnels.
AB  - Seismic design loads for tunnels are characterized in terms of the deformations
      imposed on the structure by surrounding ground. The free-field ground
      deformations due to a seismic event are estimated, and the tunnel is designed to
      accommodate these deformations. Vertically propagating shear waves are the
      predominant form of earthquake loading that causes the ovaling deformations of
      circular tunnels to develop, resulting in a distortion of the cross sectional
      shape of the tunnel lining. In this paper, seismic behavior of circular tunnels
      has been investigated due to propagation of shear waves in the vertical direction
      using quasi-static analytical approaches as well as numerical methods. Analytical
      approaches are based on the closed-form solutions which compute the forces in the
      lining due to equivalent static ovaling deformations, while the numerical method
      carries out dynamic, nonlinear soil-structure interaction analysis. Based on
      comparisons made, the accuracy and reliability of the analytical solutions are
      evaluated and discussed. The results show that the axial forces determined using
      the analytical approaches are in acceptable agreement with numerical analysis
      results, while the computed bending moments are less comparable and show
      significant discrepancies. The differences between the analytical approaches are
      also investigated and addressed. 

PMID- 24672378
TI  - Coverage extension and balancing the transmitted power of the moving relay node
      at LTE-A cellular network.
AB  - The poor capacity at cell boundaries is not enough to meet the growing demand and
      stringent design which required high capacity and throughput irrespective of
      user's location in the cellular network. In this paper, we propose new schemes
      for an optimum fixed relay node (RN) placement in LTE-A cellular network to
      enhance throughput and coverage extension at cell edge region. The proposed
      approach mitigates interferences between all nodes and ensures optimum
      utilization with the optimization of transmitted power. Moreover, we proposed a
      new algorithm to balance the transmitted power of moving relay node (MR) over
      cell size and providing required SNR and throughput at the users inside vehicle
      along with reducing the transmitted power consumption by MR. The numerical
      analysis along with the simulation results indicates that an improvement in
      capacity for users is 40% increment at downlink transmission from cell capacity.
      Furthermore, the results revealed that there is saving nearly 75% from
      transmitted power in MR after using proposed balancing algorithm. ATDI simulator
      was used to verify the numerical results, which deals with real digital
      cartographic and standard formats for terrain. 

PMID- 24672379
TI  - Modeling of task planning for multirobot system using reputation mechanism.
AB  - MOdeling of task planning for multirobot system is developed from two parts: task
      decomposition and task allocation. In the part of task decomposition, the
      conditions and processes of decomposition are elaborated. In the part of task
      allocation, the collaboration strategy, the framework of reputation mechanism,
      and three types of reputations are defined in detail, which include robot
      individual reputation, robot group reputation, and robot direct reputation. A
      time calibration function and a group calibration function are designed to
      improve the effectiveness of the proposed method and proved that they have the
      characteristics of time attenuation, historical experience related, and newly
      joined robot reward. Tasks attempt to be assigned to the robot with higher
      overall reputation, which can help to increase the success rate of the mandate
      implementation, thereby reducing the time of task recovery and redistribution.
      Player/Stage is used as the simulation platform, and three biped-robots are
      established as the experimental apparatus. The experimental results of task
      planning are compared with the other allocation methods. Simulation and
      experiment results illustrate the effectiveness of the proposed method for multi
      robot collaboration system.

PMID- 24672380
TI  - Effect of cadmium on growth, bacoside A, and bacopaside I of Bacopa monnieri
      (L.), a memory enhancing herb.
AB  - Bacopa monnieri (L.) is an important medicinal plant mainly known as a memory
      enhancing herb. It is important to see the effect of metal pollution on its
      active constituents. In this context, efforts have been made to observe the
      effect of Cd on the triterpenoid saponins bacoside A and bacopaside I in this
      plant. The influence of the metal on growth parameters like protein, chlorophyll
      content, and biomass has also been observed. It is interesting to note that the
      bacoside A and bacopaside I gradually increased by the Cd treatment up to 10 MUM
      and then decreased at higher concentrations, that is, 50 and 100 MUM, but the
      concentration of these components was more in all the treated plants as compared
      to control. On the contrary, protein, chlorophyll content, and biomass decreased
      with the increase in metal concentration and exposure duration due to metal
      toxicity.

PMID- 24672381
TI  - Nature inspired computational technique for the numerical solution of nonlinear
      singular boundary value problems arising in physiology.
AB  - We present a hybrid heuristic computing method for the numerical solution of
      nonlinear singular boundary value problems arising in physiology. The approximate
      solution is deduced as a linear combination of some log sigmoid basis functions.
      A fitness function representing the sum of the mean square error of the given
      nonlinear ordinary differential equation (ODE) and its boundary conditions is
      formulated. The optimization of the unknown adjustable parameters contained in
      the fitness function is performed by the hybrid heuristic computation algorithm
      based on genetic algorithm (GA), interior point algorithm (IPA), and active set
      algorithm (ASA). The efficiency and the viability of the proposed method are
      confirmed by solving three examples from physiology. The obtained approximate
      solutions are found in excellent agreement with the exact solutions as well as
      some conventional numerical solutions. 

PMID- 24672383
TI  - Numerical study of natural convection within a wavy enclosure using meshfree
      approach: effect of corner heating.
AB  - This paper presents a numerical study of natural convection within a wavy
      enclosure heated via corner heating. The considered enclosure is a square
      enclosure with left wavy side wall. The vertical wavy wall of the enclosure and
      both of the corner heaters are maintained at constant temperature, T c and T h ,
      respectively, with T h > T c while the remaining horizontal, bottom, top and side
      walls are insulated. A penalty element-free Galerkin approach with reduced gauss
      integration scheme for penalty terms is used to solve momentum and energy
      equations over the complex domain with wide range of parameters, namely, Rayleigh
      number (Ra), Prandtl number (Pr), and range of heaters in the x- and y-direction.
      Numerical results are represented in terms of isotherms, streamlines, and Nusselt
      number. It is observed that the rate of heat transfer depends to a great extent
      on the Rayleigh number, Prandtl number, length of the corner heaters and the
      shape of the heat transfer surface. The consistent performance of the adopted
      numerical procedure is verified by comparison of the results obtained through the
      present meshless technique with those existing in the literature. 

PMID- 24672382
TI  - An overview of important ethnomedicinal herbs of Phyllanthus species: present
      status and future prospects.
AB  - The genus Phyllanthus consists of more than 1000 species, of which many are used
      as traditional medicines. The plant extracts have been used since ancient times,
      for treating hypertension, diabetes, hepatic, urinary, and sexual disorders, and
      other common ailments. Modern day scientific investigations have now confirmed
      pharmacognostic properties of Phyllanthus herbs. The phytochemicals attributing
      these medicinal properties have been identified in many of the Phyllanthus herbs.
      The morphologically similar herbs of Phyllanthus grow together and admixture of
      species during collection for manufacture of herbal medicines is quite common.
      Hence, along with pharmacognostic and phytochemical studies, appropriate
      protocols for correct identification of species are also important. As the use of
      these herbs as green medicines is becoming more popular, it is imperative to
      assess its genetic diversity and phylogenetic relatedness for future conservation
      strategies. This review is an attempt to present an overview of the existing
      studies on pharmacognostics, phytochemistry, species identification, and genetic
      diversity of Phyllanthus herbs and consequently (i) highlight areas where further
      research is needed and (ii) draw attention towards extending similar studies in
      underutilized but potentially important herbs such as P. maderaspatensis, P.
      kozhikodianus, P. rheedii, P. scabrifolius, and P. rotundifolius. 

PMID- 24672384
TI  - Consequences of physical disturbance by tadpoles and snails on chironomid larvae.
AB  - Indirect interactions among community members impact on organisms. The effects of
      two snails, banded pond snail, Bellamya bengalensis (Lamarck), and Red-rimmed
      melania, Melanoides tuberculata (Muller), and tadpoles of Asian common toad,
      Duttaphrynus melanostictus (Schneider), on nonbiting midge larvae, Chironomus
      striatipennis Kieffer, were observed in experimental microcosm. Decrease in tube
      number and tube length of midge larvae was observed compared to control condition
      due to introduction of selected above mentioned organisms. The direct effects of
      non-predator organisms on the midge larvae are due to physical disturbance that
      destroys their tubes. This may result in vulnerability of midge larvae to
      predators in the wild. So the community structure may be altered by indirect
      effects, where one or more species, through their direct disturbance, indirectly
      change the abundance of other species. 

PMID- 24672385
TI  - The role of 18F-FDG-PET and PET/CT in patients with colorectal liver metastases
      undergoing selective internal radiation therapy with yttrium-90: a first evidence
      based review.
AB  - PURPOSE: To provide a first evidence-based review of the literature on the role
      of fluorine-18-fluorodeoxyglucose positron emission tomography and positron
      emission tomography/computed tomography (FDG-PET and PET/CT) in patients with
      colorectal liver metastases (CRLM) undergoing selective internal radiation
      therapy (SIRT) with yttrium-90 ((90)Y) microspheres. METHODS: A comprehensive
      computer literature search was conducted to find relevant published articles on
      whole-body FDG-PET or PET/CT in patients with CRLM undergoing SIRT. RESULTS: We
      identified 19 studies including 833 patients with CRLM undergoing SIRT. The role
      of FDG-PET or PET/CT was analysed in treatment planning, treatment response
      evaluation, and as prognostic tool. CONCLUSION: FDG-PET and PET/CT provide
      additional information in treatment evaluation of CRLM patients treated with SIRT
      and may have a role in treatment planning and patient selection. FDG-PET/CT is
      emerging as good prognostic tool in these patients.

PMID- 24672386
TI  - Competing endogenous RNA: the key to posttranscriptional regulation.
AB  - Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs) for microRNAs
      (miRNAs) with shared miRNAs responses elements (MREs) and act as modulator of
      miRNA by influencing the available level of miRNA. It has recently been
      discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding
      RNAs (lncRNAs), and circular RNAs act as miRNA "sponges" by sharing common MRE,
      inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements
      form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs
      are widely implicated in many biological processes. Recent studies have
      identified ceRNAs associated with a number of diseases including cancer. This
      brief review focuses on the molecular mechanism of ceRNA as part of the complex
      post-transcriptional regulatory circuit in cell and the impact of ceRNAs in
      development and disease. 

PMID- 24672387
TI  - Bioconversion of airborne methylamine by immobilized recombinant amine oxidase
      from the thermotolerant yeast Hansenula polymorpha.
AB  - Aliphatic amines, including methylamine, are air-pollutants, due to their
      intensive use in industry and the natural degradation of proteins, amino acids,
      and other nitrogen-containing compounds in biological samples. It is necessary to
      develop systems for removal of methylamine from the air, since airborne
      methylamine has a negative effect on human health. The primary amine oxidase
      (primary amine : oxygen oxidoreductase (deaminating) or amine oxidase, AMO; EC
      1.4.3.21), a copper-containing enzyme from the thermotolerant yeast Hansenula
      polymorpha which was overexpressed in baker's yeast Saccharomyces cerevisiae, was
      tested for its ability to oxidize airborne methylamine. A continuous fluidized
      bed bioreactor (CFBR) was designed to enable bioconversion of airborne
      methylamine by AMO immobilized in calcium alginate (CA) beads. The results
      demonstrated that the bioreactor with immobilized AMO eliminates nearly 97% of
      the airborne methylamine. However, the enzymatic activity of AMO causes formation
      of formaldehyde. A two-step bioconversion process was therefore proposed. In the
      first step, airborne methylamine was fed into a CFBR which contained immobilized
      AMO. In the second step, the gas flow was passed through another CFBR, with
      alcohol oxidase from the yeast H. polymorpha immobilized in CA, in order to
      decompose the formaldehyde formed in the first step. The proposed system provided
      almost total elimination of the airborne methylamine and the formaldehyde.

PMID- 24672388
TI  - On F-algebras M(p)   (1 < p < infinity) of holomorphic functions.
AB  - We consider the classes M(p)  (1 < p < infinity) of holomorphic functions on the
      open unit disk ?? in the complex plane. These classes are in fact generalizations
      of the class M introduced by Kim (1986). The space M (p) equipped with the
      topology given by the metric rho p defined by rhop (f, g) = ||f - g|| p =
      (?0(2pi) log(p) (1 + M(f - g)(theta))(dtheta/2pi))(1/p), with f, g ? M (p) and
      Mf(theta) = sup 0 ? r<1 ?|f(re(itheta))|, becomes an F-space. By a result of
      Stoll (1977), the Privalov space N(p)  (1 < p < infinity) with the topology given
      by the Stoll metric d p is an F-algebra. By using these two facts, we prove that
      the spaces M(p) and N(p) coincide and have the same topological structure.
      Consequently, we describe a general form of continuous linear functionals on M(p)
      (with respect to the metric rhop). Furthermore, we give a characterization of
      bounded subsets of the spaces M(p). Moreover, we give the examples of bounded
      subsets of M(p) that are not relatively compact.

PMID- 24672389
TI  - A PSO-based hybrid metaheuristic for permutation flowshop scheduling problems.
AB  - This paper investigates the permutation flowshop scheduling problem (PFSP) with
      the objectives of minimizing the makespan and the total flowtime and proposes a
      hybrid metaheuristic based on the particle swarm optimization (PSO). To enhance
      the exploration ability of the hybrid metaheuristic, a simulated annealing hybrid
      with a stochastic variable neighborhood search is incorporated. To improve the
      search diversification of the hybrid metaheuristic, a solution replacement
      strategy based on the pathrelinking is presented to replace the particles that
      have been trapped in local optimum. Computational results on benchmark instances
      show that the proposed PSO-based hybrid metaheuristic is competitive with other
      powerful metaheuristics in the literature. 

PMID- 24672390
TI  - Kinetic studies on fermentative production of biofuel from synthesis gas using
      Clostridium ljungdahlii.
AB  - The intrinsic growth, substrate uptake, and product formation biokinetic
      parameters were obtained for the anaerobic bacterium, Clostridium ljungdahlii,
      grown on synthesis gas in various pressurized batch bioreactors. A dual-substrate
      growth kinetic model using Luong for CO and Monod for H2 was used to describe the
      growth kinetics of the bacterium on these substrates. The maximum specific growth
      rate (MU(max) = 0.195 h(-1)) and Monod constants for CO (K s,CO = 0.855 atm) and
      H2 (K(s,H2) = 0.412 atm) were obtained. This model also accommodated the CO
      inhibitory effects on cell growth at high CO partial pressures, where no growth
      was apparent at high dissolved CO tensions (P(CO)(*) > 0.743 atm). The Volterra
      model, Andrews, and modified Gompertz were, respectively, adopted to describe the
      cell growth, substrate uptake rate, and product formation. The maximum specific
      CO uptake rate (q(max) = 34.364 mmol/g cell/h), CO inhibition constant (K(I) =
      0.601 atm), and maximum rate of ethanol (R(max) = 0.172 mmol/L/h at P(CO) = 0.598
      atm) and acetate (R(max) = 0.096 mmol/L/h at P(CO) = 0.539 atm) production were
      determined from the applied models.

PMID- 24672391
TI  - Properties of vulcanized polyisoprene rubber composites filled with opalized
      white tuff and precipitated silica.
AB  - Opalized white tuff (OWT) with 40 MUm average particle size and 39.3 m(2)/g
      specific surface area has been introduced into polyisoprene rubber (NR). Their
      reinforcing effects were evaluated by comparisons with those from precipitated
      silica (PSi). The cure characteristic, apparent activation energy of cross-link
      (E(ac)) and reversion (E(ar)), and mechanical properties of a variety of
      composites based on these rubbers were studied. This was done using vulcanization
      techniques, mechanical testing, and scanning electron microscopy (SEM). The
      results showed that OWT can greatly improve the vulcanizing process by shortening
      the time of optimum cure (t(c90)) and the scorch time (t(s2)) of cross-linked
      rubber composites, which improves production efficiency and operational security.
      The rubber composites filled with 50 phr of OWT were found to have good
      mechanical and elastomeric properties. The tensile strengths of the NR/OWT
      composites are close to those of NR/PSi composites, but the tear strength and
      modulus are not as good as the corresponding properties of those containing
      precipitated silica. Morphology results revealed that the OWT is poorly dispersed
      in the rubber matrix. According to that, the lower interactions between OWT and
      polyisoprene rubber macromolecules are obtained, but similar mechanical
      properties of NR/OWT (100/50) rubber composites compared with NR/PSi (100/50)
      rubber composites are resulted.

PMID- 24672392
TI  - Genome-wide characterisation of gene expression in rice leaf blades at 25 
      degrees C and 30  degrees C.
AB  - Rice growth is greatly affected by temperature. To examine how temperature
      influences gene expression in rice on a genome-wide basis, we utilised recently
      compiled next-generation sequencing datasets and characterised a number of RNA
      sequence transcriptome samples in rice seedling leaf blades at 25  degrees C and
      30  degrees C. Our analysis indicated that 50.4% of all genes in the rice genome
      (28,296/56,143) were expressed in rice samples grown at 25  degrees C, whereas
      slightly fewer genes (50.2%; 28,189/56,143) were expressed in rice leaf blades
      grown at 30  degrees C. Among the genes that were expressed, approximately 3%
      were highly expressed, whereas approximately 65% had low levels of expression.
      Further examination demonstrated that 821 genes had a twofold or higher increase
      in expression and that 553 genes had a twofold or greater decrease in expression
      at 25  degrees C. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) analyses suggested that the ribosome pathway and multiple metabolic
      pathways were upregulated at 25  degrees C. Based on these results, we deduced
      that gene expression at both transcriptional and translational levels was
      stimulated at 25  degrees C, perhaps in response to a suboptimal temperature
      condition. Finally, we observed that temperature markedly regulates several super
      families of transcription factors, including bZIP, MYB, and WRKY.

PMID- 24672393
TI  - Examination of the ovarian reserve after generation of unilateral rudimentary
      uterine horns in rats.
AB  - OBJECTIVE: The purpose of this experimental rat model study is to evaluate the
      changes in the ovarian environment after excision of the rudimentary horn.
      METHODS: Ten female Wistar albino rats were used in this study. One cm of right
      uterine horn length was excised in the first operation. Two months after the
      first operation, all animals were sacrificed to obtain ovaries for histological
      examination. Mann-Whitney U test and Student's t-test were used for statistical
      analysis purposes. Statistical significance was defined as P < 0.005. RESULTS:
      The number of primordial follicles (P = 0.415), primary follicles (P = 0.959),
      preantral follicles (P = 0.645), antral follicles (P = 0.328), and Graafian
      follicles (P = 0.721) was decreased and the number of atretic follicles (P =
      0.374) increased in the right ovarian side. Howeve,r this difference was not
      found to be statistically significant. CONCLUSION: The results of this
      experimental rat model study suggest that the excision of rudimentary horn could
      have negative effects on ipsilateral ovarian functions.

PMID- 24672394
TI  - A new approach in regression analysis for modeling adsorption isotherms.
AB  - Numerous regression approaches to isotherm parameters estimation appear in the
      literature. The real insight into the proper modeling pattern can be achieved
      only by testing methods on a very big number of cases. Experimentally, it cannot
      be done in a reasonable time, so the Monte Carlo simulation method was applied.
      The objective of this paper is to introduce and compare numerical approaches that
      involve different levels of knowledge about the noise structure of the analytical
      method used for initial and equilibrium concentration determination. Six levels
      of homoscedastic noise and five types of heteroscedastic noise precision models
      were considered. Performance of the methods was statistically evaluated based on
      median percentage error and mean absolute relative error in parameter estimates.
      The present study showed a clear distinction between two cases. When equilibrium
      experiments are performed only once, for the homoscedastic case, the winning
      error function is ordinary least squares, while for the case of heteroscedastic
      noise the use of orthogonal distance regression or Margart's percent standard
      deviation is suggested. It was found that in case when experiments are repeated
      three times the simple method of weighted least squares performed as well as more
      complicated orthogonal distance regression method. 

PMID- 24672396
TI  - Oversimplification and overstandardization in biological methods: sperm bioassays
      in ecotoxicology as a case of study and a proposal for their reformulation.
AB  - An interesting toxicological bioassay (fertilization inhibition in sea urchin)
      uses as assessment criterion a variable (fertilization ratio) whose variation
      with time creates two types of difficulties. First, it fails to distinguish
      between the toxic effect and the spontaneous decline in the sperm activity,
      causing some inconsistencies. Second, the sensitivity of the fertilization ratio
      to many other variables of the system requires a complex standardization,
      constraining the achievement of the method without solving its main problem. Our
      proposal consists of using a parameter (sperm half-life) as the response of the
      assay, and describing explicitly the behavior of the system as a simultaneous
      function of dose and time. This new focus is able to solve the problematic
      character of the results based on the fertilization ratio and by using the same
      data set which is required by the conventional approach; it simplifies the
      protocol, economizes experimental effort, provides unambiguous and robust
      results, and contributes to the detection of an artefactual temperature effect,
      which is not very evident under the usual perspective. Potential application of
      this new approach to the improvement of other formally similar bioassays is
      finally suggested. 

PMID- 24672395
TI  - A modified method for studying behavioral paradox of antioxidants and their
      disproportionate competitive kinetic effect to scavenge the peroxyl radical
      formation.
AB  - We have described a modified method for evaluating inhibitor of peroxyl radicals,
      a well-recognized and -documented radical involved in cancer initiation and
      promotion as well as diseases related to oxidative stress and ageing. We are
      reporting hydrophilic and lipophilic as well as natural and synthetic forms of
      antioxidants revealing a diversified behaviour to peroxyl radical in a dose
      dependent manner (1 nM-10 MUM). A simple kinetic model for the competitive
      oxidation of an indicator molecule (ABTS) and a various antioxidant by a radical
      (ROO(*)) is described. The influences of both the concentration of antioxidant
      and duration of reaction (70 min) on the inhibition of the radical cation
      absorption are taken into account while determining the activity. The induction
      time of the reaction was also proposed as a parameter enabling determination of
      antioxidant content by optimizing and introducing other kinetic parameters in 96
      well plate assays. The test evidently improves the original PRTC (peroxyl radical
      trapping capacity) assay in terms of the amount of chemical used, simultaneous
      tracking, that is, the generation of the radical taking place continually and the
      kinetic reduction technique (area under curve, peak value, slope, and Vmax).

PMID- 24672397
TI  - Synthesis and characterization of silver and gold nanoparticles using aqueous
      extract of seaweed, Turbinaria conoides, and their antimicrofouling activity.
AB  - Silver and gold nanoparticles were synthesized using an aqueous extract of the
      seaweed Turbinaria conoides and their antibiofilm activity against marine biofilm
      forming bacteria is reported here. The UV-Vis spectra showed the characteristics
      SPR absorption band for Ag NPs at 421 and for Au NPs at 538 nm. Further, the
      synthesized nanoparticles were characterized using FT-IR, XRD, FESEM, EDX, and
      HRTEM analysis. Spherical and triangular nanostructures of the Ag and Au
      nanoparticles were observed between the size ranges of 2-17 nm and 2-19 nm,
      respectively. The synthesized Ag NPs are efficient in controlling the bacterial
      biofilm formation; however, Au NPs did not show any remarkable antibiofilm
      activity. The maximum zone of inhibition was recorded against E. coli (17.6 +/-
      0.42 mm), followed by Salmonella sp., S. liquefaciens, and A. hydrophila. The
      macrotube dilution method inferred the MIC (20-40 uL mL(-1)) and MBC (40-60 uL
      mL(-1)) of Ag NPs. The CLSM images clearly showed the weak adherence and
      disintegrating biofilm formation of marine biofilm bacterial strains treated with
      Ag NPs. The Artemia cytotoxicity assay recorded the LC50 value of 88.914 +/- 5.04
      uL mL(-1). Thus the present study proved the efficiency of Ag NPs as a potent
      antimicrofouling agent and became the future perspective for the possible usage
      in the biofouling related issues in the aquaculture installations and other
      marine systems.

PMID- 24672398
TI  - Biogenic hydrogen conversion of de-oiled jatropha waste via anaerobic sequencing
      batch reactor operation: process performance, microbial insights, and CO2
      reduction efficiency.
AB  - We report the semicontinuous, direct (anaerobic sequencing batch reactor
      operation) hydrogen fermentation of de-oiled jatropha waste (DJW). The effect of
      hydraulic retention time (HRT) was studied and results show that the stable and
      peak hydrogen production rate of 1.48 L/L * d and hydrogen yield of 8.7 mL H2/g
      volatile solid added were attained when the reactor was operated at HRT 2 days
      (d) with a DJW concentration of 200 g/L, temperature 55  degrees C, and pH 6.5.
      Reduced HRT enhanced the production performance until 1.75 d. Further reduction
      has lowered the process efficiency in terms of biogas production and hydrogen gas
      content. The effluent from hydrogen fermentor was utilized for methane
      fermentation in batch reactors using pig slurry and cow dung as seed sources. The
      results revealed that pig slurry was a feasible seed source for methane
      generation. Peak methane production rate of 0.43 L CH4/L * d and methane yield of
      20.5 mL CH4/g COD were observed at substrate concentration of 10 g COD/L,
      temperature 30  degrees C, and pH 7.0. PCR-DGGE analysis revealed that
      combination of cellulolytic and fermentative bacteria were present in the
      hydrogen producing ASBR.

PMID- 24672399
TI  - Research on the material removal in the polishing of potassium dihydrogen
      phosphate crystals based on deliquescent action.
AB  - Through the polishing experiments of potassium dihydrogen phosphate (KDP)
      crystals based on deliquescent action, the effect of several major factors,
      including crystal's initial surface state, polishing time, and revolution of
      polishing plate, on material removal was researched. Under certain experimental
      conditions, the rules of material removal were reached, and experimental results
      are discussed, which lays the foundation for popularization and application of
      polishing technology for KDP crystals based on deliquescent action. 

PMID- 24672400
TI  - Application of nanometal oxides in situ in nonwoven polyester fabric for the
      removal of bacterial indicators of pollution from wastewater.
AB  - The objective of this study is to investigate and assess the use of in situ
      deposit nanosilver (nAg2O) or nanocopper oxides (nCuO) into nonwoven polyester
      fabric (NWPF) as a safe and effective antibacterial filter of pollution from
      domestic wastewater. The bactericidal effect of both nAg2O and nCuO was examined
      against Gram-negative bacteria (Escherichia coli, Salmonella typhi) and Gram
      positive bacteria (Enterococcus faecalis, Staphylococcus aureus) using agar
      diffusion disk method. In addition, the capability of nAg2O and nCuO as
      disinfectants for secondary treated domestic wastewater was investigated as a
      case study. Transmission electron microscope (TEM) confirmed the formation of
      nAg2O and nCuO particles with average particle sizes of 15 and 41 nm,
      respectively. Disk diffusion results showed that nAg2O had a higher bactericidal
      effect than nCuO. Moreover, the disinfection of secondary treated wastewater
      using 1.27 mg/cm(3) of nAg2O in the nonwoven fabric was capable of hindering
      99.6% and 91.7% of total and fecal coliforms within 10 minutes with a residual
      value of 18 and 15 MPN-index/100 mL, respectively. The residual total and fecal
      coliform concentrations were far less than that stated in the national and
      international limits for wastewater reuse in agriculture purpose.

PMID- 24672401
TI  - Formulation and characterization of drug loaded nonionic surfactant vesicles
      (niosomes) for oral bioavailability enhancement.
AB  - Nonionic surfactant vesicles (niosomes) were formulated with an aim of enhancing
      the oral bioavailability of tenofovir disoproxil fumarate (TDF), an anti-HIV
      drug. Niosomes were formulated by conventional thin film hydration technique with
      different molar ratios of surfactant, cholesterol, and dicetyl phosphate. The
      formulated niosomes were found spherical in shape, ranging from 2.95 MUm to 10.91
      MUm in size. Vesicles with 1 : 1 : 0.1 ratios of surfactant : cholesterol :
      dicetyl phosphate with each grade of span were found to have higher entrapment
      efficiencies, which were further selected for in vitro and in vivo studies.
      Vesicles formulated with sorbitan monostearate were found to have maximum drug
      release (99.091%) at the end of 24 hours and followed zero order release
      kinetics. The results of in vivo study revealed that the niosomes significantly
      enhanced the oral bioavailability of TDF in rats after a dose of 95 mg/kg. The
      average relative bioavailability of niosomes in relation to plane drug solution
      was found to be 2.58, indicating more than twofold increase in oral
      bioavailability of TDF. Significant increase in mean residential time (MRT) was
      also found, reflecting release retarding efficacy of the vesicles. In conclusion,
      niosomes could be a promising delivery for TDF with improved oral bioavailability
      and prolonged release profiles.

PMID- 24672402
TI  - Constructing better classifier ensemble based on weighted accuracy and diversity
      measure.
AB  - A weighted accuracy and diversity (WAD) method is presented, a novel measure used
      to evaluate the quality of the classifier ensemble, assisting in the ensemble
      selection task. The proposed measure is motivated by a commonly accepted
      hypothesis; that is, a robust classifier ensemble should not only be accurate but
      also different from every other member. In fact, accuracy and diversity are
      mutual restraint factors; that is, an ensemble with high accuracy may have low
      diversity, and an overly diverse ensemble may negatively affect accuracy. This
      study proposes a method to find the balance between accuracy and diversity that
      enhances the predictive ability of an ensemble for unknown data. The quality
      assessment for an ensemble is performed such that the final score is achieved by
      computing the harmonic mean of accuracy and diversity, where two weight
      parameters are used to balance them. The measure is compared to two
      representative measures, Kappa-Error and GenDiv, and two threshold measures that
      consider only accuracy or diversity, with two heuristic search algorithms,
      genetic algorithm, and forward hill-climbing algorithm, in ensemble selection
      tasks performed on 15 UCI benchmark datasets. The empirical results demonstrate
      that the WAD measure is superior to others in most cases. 

PMID- 24672403
TI  - Seasonal changes of fish assemblages in a subtropical lagoon in the SE Gulf of
      California.
AB  - The composition and seasonal changes of the fish assemblage in a coastal lagoon
      system in southeastern Gulf of California were assessed from December 2001 to
      July 2005. A total of 20,877 organisms belonging to 191 species and 47 families
      were analyzed. We determined that almost all the species inhabiting the system
      were found; however some rare species were not captured in our study. The
      majority of the species found were demersal but in every season at least one
      pelagic or benthopelagic species showed high abundances. The moonfish, Selene
      peruviana, was the most abundant species, whilst the puffer, Sphoeroides
      annulatus, was the main species in terms of biomass. The species composition
      changed seasonally; results from the Simpson diversity index and the cumulative
      species curve show that seasonally almost all the species in the system for a
      given season were found. These changes were also reflected in the multivariate
      results. The seasonal variations could be attributed to the migration of species
      out of the system as they grow and the arrival of new ones, which could also be
      related to temperature patterns since this environmental factor changes
      considerably through the year. 

PMID- 24672404
TI  - Prediction and analysis of surface hydrophobic residues in tertiary structure of
      proteins.
AB  - The analysis of protein structures provides plenty of information about the
      factors governing the folding and stability of proteins, the preferred amino
      acids in the protein environment, the location of the residues in the
      interior/surface of a protein and so forth. In general, hydrophobic residues such
      as Val, Leu, Ile, Phe, and Met tend to be buried in the interior and polar side
      chains exposed to solvent. The present work depends on sequence as well as
      structural information of the protein and aims to understand nature of
      hydrophobic residues on the protein surfaces. It is based on the nonredundant
      data set of 218 monomeric proteins. Solvent accessibility of each protein was
      determined using NACCESS software and then obtained the homologous sequences to
      understand how well solvent exposed and buried hydrophobic residues are
      evolutionarily conserved and assigned the confidence scores to hydrophobic
      residues to be buried or solvent exposed based on the information obtained from
      conservation score and knowledge of flanking regions of hydrophobic residues. In
      the absence of a three-dimensional structure, the ability to predict surface
      accessibility of hydrophobic residues directly from the sequence is of great help
      in choosing the sites of chemical modification or specific mutations and in the
      studies of protein stability and molecular interactions. 

PMID- 24672405
TI  - View-dependent tessellation and simulation of ocean surfaces.
AB  - Modeling and rendering realistic ocean scenes have been thoroughly investigated
      for many years. Its appearance has been studied and it is possible to find very
      detailed simulations where a high degree of realism is achieved. Nevertheless,
      among the solutions to ocean rendering, real-time management of the huge
      heightmaps that are necessary for rendering an ocean scene is still not solved.
      We propose a new technique for simulating the ocean surface on GPU. This
      technique is capable of offering view-dependent approximations of the mesh while
      maintaining coherence among the extracted approximations. This feature is very
      important as most solutions previously presented must retessellate from the
      initial mesh. Our solution is able to use the latest extracted approximation when
      refining or coarsening the mesh. 

PMID- 24672406
TI  - Cloning and characterization of a flavonol synthase gene from Scutellaria
      baicalensis.
AB  - Flavonols are the most abundant of all the flavonoids and play pivotal roles in a
      variety of plants. We isolated a cDNA clone encoding flavonol synthase from
      Scutellaria baicalensis (SbFLS). The SbFLS cDNA is 1011 bp long, encodes 336
      amino acid residues, and belongs to a family of 2-oxoglutarate-dependent
      dioxygenases. The overall structure of SbFLS is very similar to that of
      Arabidopsis thaliana anthocyanidin synthase (AtANS), with a beta jelly-roll fold
      surrounded by tens of short and long alpha-helices. SbFLS was constitutively
      expressed in the roots, stems, leaves, and flowers, with particularly high
      expression in the roots and flowers. SbFLS transcript levels in the roots were
      376-, 70-, and 2.5-fold higher than in the leaves, stems, and flowers. The
      myricetin content was significantly higher than that of kaempferol and quercetin.
      Therefore, we suggest that SbFLS mediates flavonol formation in the different
      organs of S. baicalensis. Our study may contribute to the knowledge of the role
      of FLS in S. baicalensis.

PMID- 24672408
TI  - Letter from the editor.

PMID- 24672407
TI  - Biosmart materials: breaking new ground in dentistry.
AB  - By definition and general agreement, smart materials are materials that have
      properties which may be altered in a controlled fashion by stimuli, such as
      stress, temperature, moisture, pH, and electric or magnetic fields. There are
      numerous types of smart materials, some of which are already common. Examples
      include piezoelectric materials, which produce a voltage when stress is applied
      or vice versa, shape memory alloys or shape memory polymers which are
      thermoresponsive, and pH sensitive polymers which swell or shrink as a response
      to change in pH. Thus, smart materials respond to stimuli by altering one or more
      of their properties. Smart behaviour occurs when a material can sense some
      stimulus from its environment and react to it in a useful, reliable,
      reproducible, and usually reversible manner. These properties have a beneficial
      application in various fields including dentistry. Shape memory alloys, zirconia,
      and smartseal are examples of materials exhibiting a smart behavior in dentistry.
      There is a strong trend in material science to develop and apply these
      intelligent materials. These materials would potentially allow new and
      groundbreaking dental therapies with a significantly enhanced clinical outcome of
      treatments. 

PMID- 24672409
TI  - Direct-acting antiviral agents in patients with hepatitis C cirrhosis.
AB  - Patients with cirrhosis who are infected with hepatitis C virus (HCV) are the
      most in need of antiviral treatment. Virologic cure improves fibrosis and quality
      of life while reducing liver-related morbidity and mortality. In mid-2011, the
      addition of direct-acting antiviral agents (DAAs)-the protease inhibitors
      boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex)-to pegylated
      interferon alpha-2a/b and ribavirin revolutionized the treatment of HCV infection
      by increasing cure rates across all fibrosis scores in patients with genotype 1
      HCV infection. However, patients with advanced fibrosis or cirrhosis are the most
      difficult to treat, and the addition of DAAs increases treatment side effects as
      well as potency. Five phase III DAA trials have been published to date, but they
      contain limited data on patients with cirrhosis. This review will examine the
      available data and will describe the evolution of HCV therapy in patients with
      cirrhosis from the standard-of-care therapy of the past decade into the new era
      of DAAs. 

PMID- 24672410
TI  - Low-FODMAP Diet for Treatment of Irritable Bowel Syndrome.
AB  - Functional bowel disorders, including irritable bowel syndrome (IBS), are common
      disorders that have a significant impact on patients' quality of life. These
      disorders present major challenges to healthcare providers, as few effective
      medical therapies are currently available. Recently, there has been increasing
      interest in dietary therapies for IBS, particularly a diet low in fermentable
      oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Since
      ingestion of FODMAPs increases the delivery of readily fermentable substrates and
      water to the distal small intestine and colon-which results in luminal distention
      and gas-the reduction of FODMAPs in a patient's diet may improve functional
      gastrointestinal symptoms. This paper will review the pathophysiology of IBS and
      the role of FODMAPs for the treatment of this condition. 

PMID- 24672412
TI  - Could vitamin d supplementation benefit patients with chronic liver disease?

PMID- 24672411
TI  - Assessing disease activity in patients with ulcerative colitis.

PMID- 24672413
TI  - Cryotherapy for the eradication of barrett esophagus or early cancer.

PMID- 24672414
TI  - Treatment of gastroesophageal reflux disease during pregnancy.

PMID- 24672415
TI  - Langerhans cell histiocytosis and choledocholithiasis: a causal relationship or
      coincidence?

PMID- 24672416
TI  - Langerhans cell histiocytosis and choledocholithiasis: is there an association?

PMID- 24672417
TI  - Gastric phytobezoar dissolution with ingestion of diet coke and cellulase.

PMID- 24672418
TI  - Gastrointestinal bezoars: history and current treatment paradigms.

PMID- 24672419
TI  - Integrated end of life care: the role of social services.

PMID- 24672421
TI  - Activity in dlPFC and its effective connectivity to vmPFC are associated with
      temporal discounting.
AB  - There is widespread interest in identifying computational and neurobiological
      mechanisms that influence the ability to choose long-term benefits over more
      proximal and readily available rewards in domains such as dietary and economic
      choice. We present the results of a human fMRI study that examines how neural
      activity relates to observed individual differences in the discounting of future
      rewards during an intertemporal monetary choice task. We found that a region of
      left dorsolateral prefrontal cortex (dlPFC) BA-46 was more active in trials where
      subjects chose delayed rewards, after controlling for the subjective value of
      those rewards. We also found that the connectivity from dlPFC BA-46 to a region
      of ventromedial prefrontal cortex (vmPFC) widely associated with the computation
      of stimulus values, increased at the time of choice, and especially during trials
      in which subjects chose delayed rewards. Finally, we found that estimates of
      effective connectivity between these two regions played a critical role in
      predicting out-of-sample, between-subject differences in discount rates. Together
      with previous findings in dietary choice, these results suggest that a common set
      of computational and neurobiological mechanisms facilitate choices in favor of
      long-term reward in both settings. 

PMID- 24672422
TI  - A mixed-signal implementation of a polychronous spiking neural network with delay
      adaptation.
AB  - We present a mixed-signal implementation of a re-configurable polychronous
      spiking neural network capable of storing and recalling spatio-temporal patterns.
      The proposed neural network contains one neuron array and one axon array. Spike
      Timing Dependent Delay Plasticity is used to fine-tune delays and add dynamics to
      the network. In our mixed-signal implementation, the neurons and axons have been
      implemented as both analog and digital circuits. The system thus consists of one
      FPGA, containing the digital neuron array and the digital axon array, and one
      analog IC containing the analog neuron array and the analog axon array. The
      system can be easily configured to use different combinations of each. We present
      and discuss the experimental results of all combinations of the analog and
      digital axon arrays and the analog and digital neuron arrays. The test results
      show that the proposed neural network is capable of successfully recalling more
      than 85% of stored patterns using both analog and digital circuits. 

PMID- 24672420
TI  - How musical training affects cognitive development: rhythm, reward and other
      modulating variables.
AB  - Musical training has recently gained additional interest in education as
      increasing neuroscientific research demonstrates its positive effects on brain
      development. Neuroimaging revealed plastic changes in the brains of adult
      musicians but it is still unclear to what extent they are the product of
      intensive music training rather than of other factors, such as preexisting
      biological markers of musicality. In this review, we synthesize a large body of
      studies demonstrating that benefits of musical training extend beyond the skills
      it directly aims to train and last well into adulthood. For example, children who
      undergo musical training have better verbal memory, second language pronunciation
      accuracy, reading ability and executive functions. Learning to play an instrument
      as a child may even predict academic performance and IQ in young adulthood. The
      degree of observed structural and functional adaptation in the brain correlates
      with intensity and duration of practice. Importantly, the effects on cognitive
      development depend on the timing of musical initiation due to sensitive periods
      during development, as well as on several other modulating variables. Notably, we
      point to motivation, reward and social context of musical education, which are
      important yet neglected factors affecting the long-term benefits of musical
      training. Further, we introduce the notion of rhythmic entrainment and suggest
      that it may represent a mechanism supporting learning and development of
      executive functions. It also hones temporal processing and orienting of attention
      in time that may underlie enhancements observed in reading and verbal memory. We
      conclude that musical training uniquely engenders near and far transfer effects,
      preparing a foundation for a range of skills, and thus fostering cognitive
      development. 

PMID- 24672423
TI  - CRF and urocortin peptides as modulators of energy balance and feeding behavior
      during stress.
AB  - Early on, corticotropin-releasing factor (CRF), a hallmark brain peptide
      mediating many components of the stress response, was shown to affect food intake
      inducing a robust anorexigenic response when injected into the rodent brain.
      Subsequently, other members of the CRF signaling family have been identified,
      namely urocortin (Ucn) 1, Ucn 2, and Ucn 3 which were also shown to decrease food
      intake upon central or peripheral injection. However, the kinetics of feeding
      suppression was different with an early decrease following
      intracerebroventricular injection of CRF and a delayed action of Ucns contrasting
      with the early onset after systemic injection. CRF and Ucns bind to two distinct
      G-protein coupled membrane receptors, the CRF1 and CRF2. New pharmacological
      tools such as highly selective peptide CRF1 or CRF2 agonists or antagonists along
      with genetic knock-in or knock-out models have allowed delineating the primary
      role of CRF2 involved in the anorexic response to exogenous administration of CRF
      and Ucns. Several stressors trigger behavioral changes including suppression of
      feeding behavior which are mediated by brain CRF receptor activation. The present
      review will highlight the state-of-knowledge on the effects and mechanisms of
      action of CRF/Ucns-CRF1/2 signaling under basal conditions and the role in the
      alterations of food intake in response to stress. 

PMID- 24672424
TI  - Vascular regulation of adult neurogenesis under physiological and pathological
      conditions.
AB  - Neural stem cells in the mammalian adult brain continuously produce new neurons
      throughout life. Accumulating evidence in rodents suggests that various aspects
      of adult neurogenesis, including the genesis, migration, and maturation of new
      neurons, are regulated by factors derived from blood vessels and their
      microenvironment. Brain injury enhances both neurogenesis and angiogenesis,
      thereby promoting the cooperative regeneration of neurons and blood vessels. In
      this paper, we briefly review the mechanisms for the vascular regulation of adult
      neurogenesis in the ventricular-subventricular zone under physiological and
      pathological conditions, and discuss their clinical potential for brain
      regeneration strategies. 

PMID- 24672425
TI  - Atrial natriuretic factor receptor guanylate cyclase, ANF-RGC, transduces two
      independent signals, ANF and Ca(2+).
AB  - Atrial natriuretic factor receptor guanylate cyclase (ANF-RGC), was the first
      discovered member of the mammalian membrane guanylate cyclase family. The
      hallmark feature of the family is that a single protein contains both the site
      for recognition of the regulatory signal and the ability to transduce it into the
      production of the second messenger, cyclic GMP. For over two decades, the family
      has been classified into two subfamilies, the hormone receptor subfamily with ANF
      RGC being its paramount member, and the Ca(2+) modulated subfamily, which
      includes the rod outer segment guanylate cyclases, ROS-GC1 and 2, and the
      olfactory neuroepithelial guanylate cyclase. ANF-RGC is the receptor and the
      signal transducer of the most hypotensive hormones, ANF- and B-type natriuretic
      peptide (BNP). After binding these hormones at the extracellular domain it, at
      its intracellular domain, signals activation of the C-terminal catalytic module
      and accelerates the production of cyclic GMP. Cyclic GMP then serves the second
      messenger role in biological responses of ANF and BNP such as natriuresis,
      diuresis, vasorelaxation, and anti-proliferation. Very recently another modus
      operandus for ANF-RGC was revealed. Its crux is that ANF-RGC activity is also
      regulated by Ca(2+). The Ca(2+) sensor neurocalcin d mediates this signaling
      mechanism. Strikingly, the Ca(2+) and ANF signaling mechanisms employ separate
      structural motifs of ANF-RGC in modulating its core catalytic domain in
      accelerating the production of cyclic GMP. In this review the biochemistry and
      physiology of these mechanisms with emphasis on cardiovascular regulation will be
      discussed. 

PMID- 24672426
TI  - Mechanisms regulating neuronal excitability and seizure development following
      mTOR pathway hyperactivation.
AB  - The phosphatidylinositol-3-kinase/phosphatase and tensin homolog (PTEN)-mammalian
      target of rapamycin (mTOR) pathway regulates a variety of neuronal functions,
      including cell proliferation, survival, growth, and plasticity. Dysregulation of
      the pathway is implicated in the development of both genetic and acquired
      epilepsies. Indeed, several causal mutations have been identified in patients
      with epilepsy, the most prominent of these being mutations in PTEN and tuberous
      sclerosis complexes 1 and 2 (TSC1, TSC2). These genes act as negative regulators
      of mTOR signaling, and mutations lead to hyperactivation of the pathway. Animal
      models deleting PTEN, TSC1, and TSC2 consistently produce epilepsy phenotypes,
      demonstrating that increased mTOR signaling can provoke neuronal
      hyperexcitability. Given the broad range of changes induced by altered mTOR
      signaling, however, the mechanisms underlying seizure development in these
      animals remain uncertain. In transgenic mice, cell populations with hyperactive
      mTOR have many structural abnormalities that support recurrent circuit formation,
      including somatic and dendritic hypertrophy, aberrant basal dendrites, and
      enlargement of axon tracts. At the functional level, mTOR hyperactivation is
      commonly, but not always, associated with enhanced synaptic transmission and
      plasticity. Moreover, these populations of abnormal neurons can affect the larger
      network, inducing secondary changes that may explain paradoxical findings
      reported between cell and network functioning in different models or at different
      developmental time points. Here, we review the animal literature examining the
      link between mTOR hyperactivation and epileptogenesis, emphasizing the impact of
      enhanced mTOR signaling on neuronal form and function. 

PMID- 24672428
TI  - Caenorhabditis elegans glia modulate neuronal activity and behavior.
AB  - Glial cells of Caenorhabditis elegans can modulate neuronal activity and
      behavior, which is the focus of this review. Initially, we provide an overview of
      neuroglial evolution, making a comparison between C. elegans glia and their
      genealogical counterparts. What follows is a brief discussion on C. elegans glia
      characteristics in terms of their exact numbers, germ layers origin, their
      necessity for proper development of sensory organs, and lack of their need for
      neuronal survival. The more specific roles that various glial cells have on
      neuron-based activity/behavior are succinctly presented. The cephalic sheath glia
      are important for development, maintenance and activity of central synapses,
      whereas the amphid glia seem to set the tone of sensory synapses; these glial
      cell types are ectoderm-derived. Mesoderm-derived Glial-Like cells in the nerve
      Ring (GLRs) appear to be a part of the circuit for production of motor movement
      of the worm anterior. Finally, we discuss tools and approaches utilized in
      studying C. elegans glia, which are assets available for this animal, making it
      an appealing model, not only in neurosciences, but in biology in general. 

PMID- 24672427
TI  - Structural diversity of neuronal calcium sensor proteins and insights for
      activation of retinal guanylyl cyclase by GCAP1.
AB  - Neuronal calcium sensor (NCS) proteins, a sub-branch of the calmodulin
      superfamily, are expressed in the brain and retina where they transduce calcium
      signals and are genetically linked to degenerative diseases. The amino acid
      sequences of NCS proteins are highly conserved but their physiological functions
      are quite different. Retinal recoverin controls Ca(2) (+)-dependent inactivation
      of light-excited rhodopsin during phototransduction, guanylyl cyclase activating
      proteins 1 and 2 (GCAP1 and GCAP2) promote Ca(2) (+)-dependent activation of
      retinal guanylyl cyclases, and neuronal frequenin (NCS-1) modulates synaptic
      activity and neuronal secretion. Here we review the molecular structures of
      myristoylated forms of NCS-1, recoverin, and GCAP1 that all look very different,
      suggesting that the attached myristoyl group helps to refold these highly
      homologous proteins into different three-dimensional folds. Ca(2) (+)-binding to
      both recoverin and NCS-1 cause large protein conformational changes that ejects
      the covalently attached myristoyl group into the solvent exterior and promotes
      membrane targeting (Ca(2) (+)-myristoyl switch). The GCAP proteins undergo much
      smaller Ca(2) (+)-induced conformational changes and do not possess a Ca(2) (+)
      myristoyl switch. Recent structures of GCAP1 in both its activator and Ca(2) (+)
      bound inhibitory states will be discussed to understand structural determinants
      that control their Ca(2) (+)-dependent activation of retinal guanylyl cyclases. 

PMID- 24672429
TI  - microRNAs in axon guidance.
AB  - Brain wiring is a highly intricate process in which trillions of neuronal
      connections are established. Its initial phase is particularly crucial in
      establishing the general framework of neuronal circuits. During this early step,
      differentiating neurons extend axons, which reach their target by navigating
      through a complex environment with extreme precision. Research in the past 20
      years has unraveled a vast and complex array of chemotropic cues that guide the
      leading tip of axons, the growth cone, throughout its journey. Tight regulation
      of these cues, and of their receptors and signaling pathways, is necessary for
      the high degree of accuracy required during circuit formation. However, little is
      known about the nature of regulatory molecules or mechanisms fine-tuning axonal
      cue response. Here we review recent, and somewhat fragmented, research on the
      possibility that microRNAs (miRNAs) could be key fine-tuning regulatory molecules
      in axon guidance. miRNAs appear to shape long-range axon guidance, fasciculation
      and targeting. We also present several lines of evidence suggesting that miRNAs
      could have a compartmentalized and differential action at the cell soma, and
      within axons and growth cones. 

PMID- 24672430
TI  - A seeded propagation of Cu, Zn-superoxide dismutase aggregates in amyotrophic
      lateral sclerosis.
AB  - Abnormal accumulation of protein inclusions in motor neurons has been known as a
      major pathological change in amyotrophic lateral sclerosis (ALS). Increasing
      numbers of proteins including mutant Cu, Zn-superoxide dismutase (SOD1) have been
      identified as constituents of pathological inclusions in a form of insoluble
      fibrillar aggregates. Notably, protein fibrillar aggregates exhibit a self
      perpetuating property, which can convert a soluble native protein into insoluble
      fibrillar aggregates. Such "seeding reaction" of protein fibrils can accelerate
      the aggregation significantly and would contribute to the spread of inclusion
      pathologies from an affected cell to its neighboring cells in neurodegenerative
      diseases. In ALS, a pathological change first occurs at the site of disease onset
      and then propagates throughout the affected tissues in a time-dependent manner;
      therefore, it can be assumed that seeded aggregation may be the key factor of
      disease progression in ALS. In this mini review, we will briefly summarize recent
      studies on possible roles of a seeded aggregation of SOD1 in pathomechanism of
      ALS. 

PMID- 24672431
TI  - A major role for Tau in neuronal DNA and RNA protection in vivo under
      physiological and hyperthermic conditions.
AB  - Nucleic acid protection is a substantial challenge for neurons, which are
      continuously exposed to oxidative stress in the brain. Neurons require powerful
      mechanisms to protect DNA and RNA integrity and ensure their functionality and
      longevity. Beside its well known role in microtubule dynamics, we recently
      discovered that Tau is also a key nuclear player in the protection of neuronal
      genomic DNA integrity under reactive oxygen species (ROS)-inducing heat stress
      (HS) conditions in primary neuronal cultures. In this report, we analyzed the
      capacity of Tau to protect neuronal DNA integrity in vivo in adult mice under
      physiological and HS conditions. We designed an in vivo mouse model of
      hyperthermia/HS to induce a transient increase in ROS production in the brain.
      Comet and Terminal deoxyribonucleotidyltransferase-mediated deoxyuridine
      triphosphate nick end labeling (TUNEL) assays demonstrated that Tau protected
      genomic DNA in adult cortical and hippocampal neurons in vivo under physiological
      conditions in wild-type (WT) and Tau-deficient (KO-Tau) mice. HS increased DNA
      breaks in KO-Tau neurons. Notably, KO-Tau hippocampal neurons in the CA1 subfield
      restored DNA integrity after HS more weakly than the dentate gyrus (DG) neurons.
      The formation of phosphorylated histone H2AX foci, a double-strand break marker,
      was observed in KO-Tau neurons only after HS, indicating that Tau deletion did
      not trigger similar DNA damage under physiological or HS conditions. Moreover,
      genomic DNA and cytoplasmic and nuclear RNA integrity were altered under HS in
      hippocampal neurons exhibiting Tau deficiency, which suggests that Tau also
      modulates RNA metabolism. Our results suggest that Tau alterations lead to a loss
      of its nucleic acid safeguarding functions and participate in the accumulation of
      DNA and RNA oxidative damage observed in the Alzheimer's disease (AD) brain. 

PMID- 24672432
TI  - Glycinergic transmission modulates GABAergic inhibition in the avian auditory
      pathway.
AB  - For all neurons, a proper balance of synaptic excitation and inhibition is
      crucial to effect computational precision. Achievement of this balance is
      remarkable when one considers factors that modulate synaptic strength operate on
      multiple overlapping time scales and affect both pre- and postsynaptic elements.
      Recent studies have shown that inhibitory transmitters, glycine and GABA, are co
      released in auditory nuclei involved in the computation of interaural time
      disparities (ITDs), a cue used to process sound source location. The co-release
      expressed at these synapses is heavily activity dependent, and generally occurs
      when input rates are high. This circuitry, in both birds and mammals, relies on
      inhibitory input to maintain the temporal precision necessary for ITD encoding.
      Studies of co-release in other brain regions suggest that GABA and glycine
      receptors (GlyRs) interact via cross-suppressive modulation of receptor
      conductance. We performed in vitro whole-cell recordings in several nuclei of the
      chicken brainstem auditory circuit to assess whether this cross-suppressive
      phenomenon was evident in the avian brainstem. We evaluated the effect of
      pressure-puff applied glycine on synaptically evoked inhibitory currents in
      nucleus magnocellularis (NM) and the superior olivary nucleus (SON). Glycine pre
      application reduced the amplitude of inhibitory postsynaptic currents (IPSCs)
      evoked during a 100 Hz train stimulus in both nuclei. This apparent glycinergic
      modulation was blocked in the presence of strychnine. Further experiments showed
      that this modulation did not depend on postsynaptic biochemical interactions such
      as phosphatase activity, or direct interactions between GABA and GlyR proteins.
      Rather, voltage clamp experiments in which we manipulated Cl(-) flux during
      agonist application suggest that activation of one receptor will modulate the
      conductance of the other via local changes in Cl(-) ion concentration within
      microdomains of the postsynaptic membrane. 

PMID- 24672434
TI  - Distribution of nanoparticles throughout the cerebral cortex of rodents and non
      human primates: Implications for gene and drug therapy.
AB  - When nanoparticles/proteins are infused into the brain, they are often
      transported to distal sites in a manner that is dependent both on the
      characteristics of the infusate and the region targeted. We have previously shown
      that adeno-associated virus (AAV) is disseminated within the brain by
      perivascular flow and also by axonal transport. Perivascular distribution usually
      does not depend strongly on the nature of the infusate. Many proteins, neutral
      liposomes and AAV particles distribute equally well by this route when infused
      under pressure into various parenchymal locations. In contrast, axonal transport
      requires receptor-mediated uptake of AAV by neurons and engagement with specific
      transport mechanisms previously demonstrated for other neurotropic viruses.
      Cerebrospinal fluid (CSF) represents yet another way in which brain anatomy may
      be exploited to distribute nanoparticles broadly in the central nervous system.
      In this study, we assessed the distribution and perivascular transport of
      nanoparticles of different sizes delivered into the parenchyma of rodents and CSF
      in non-human primates. 

PMID- 24672433
TI  - Interaction between the 5-HT system and the basal ganglia: functional implication
      and therapeutic perspective in Parkinson's disease.
AB  - The neurotransmitter serotonin (5-HT) has a multifaceted function in the
      modulation of information processing through the activation of multiple receptor
      families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7)
      and ligand-gated ion channels (5-HT3). The largest population of serotonergic
      neurons is located in the midbrain, specifically in the raphe nuclei. Although
      the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the
      basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The
      BG are a highly organized network of subcortical nuclei composed of the striatum
      (caudate and putamen), subthalamic nucleus (STN), internal and external globus
      pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia
      nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the
      cortico-BG-thalamic circuits, which play a role in many functions like motor
      control, emotion, and cognition and are critically involved in diseases such as
      Parkinson's disease (PD). This review provides an overview of serotonergic
      modulation of the BG at the functional level and a discussion of how this
      interaction may be relevant to treating PD and the motor complications induced by
      chronic treatment with L-DOPA. 

PMID- 24672435
TI  - Localization of peroxisome proliferator-activated receptor alpha (PPARalpha) and
      N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing
      the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult
      rat hippocampus.
AB  - The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and
      palmithylethanolamide (PEA) are known to be endogenous ligands of PPARalpha
      receptors, and their presence requires the activation of a specific phospholipase
      D (NAPE-PLD) associated with intracellular Ca(2+) fluxes. Thus, the
      identification of a specific population of NAPE-PLD/PPARalpha-containing neurons
      that express selective Ca(2+)-binding proteins (CaBPs) may provide a
      neuroanatomical basis to better understand the PPARalpha system in the brain. For
      this purpose, we used double-label immunofluorescence and confocal laser scanning
      microscopy for the characterization of the co-existence of NAPE-PLD/PPARalpha and
      the CaBPs calbindin D28k, calretinin and parvalbumin in the rat hippocampus.
      PPARalpha expression was specifically localized in the cell nucleus and,
      occasionally, in the cytoplasm of the principal cells (dentate granular and CA
      pyramidal cells) and some non-principal cells of the hippocampus. PPARalpha was
      expressed in the calbindin-containing cells of the granular cell layer of the
      dentate gyrus (DG) and the SP of CA1. These principal PPARalpha(+)/calbindin(+)
      cells were closely surrounded by NAPE-PLD(+) fiber varicosities. No pyramidal
      PPARalpha(+)/calbindin(+) cells were detected in CA3. Most cells containing
      parvalbumin expressed both NAPE-PLD and PPARalpha in the principal layers of the
      DG and CA1/3. A small number of cells containing PPARalpha and calretinin was
      found along the hippocampus. Scattered NAPE-PLD(+)/calretinin(+) cells were
      specifically detected in CA3. NAPE-PLD(+) puncta surrounded the calretinin(+)
      cells localized in the principal cells of the DG and CA1. The identification of
      the hippocampal subpopulations of NAPE-PLD/PPARalpha-containing neurons that
      express selective CaBPs should be considered when analyzing the role of
      NAEs/PPARalpha-signaling system in the regulation of hippocampal functions. 

PMID- 24672436
TI  - The Michelin red guide of the brain: role of dopamine in goal-oriented
      navigation.
AB  - Spatial learning has been recognized over the years to be under the control of
      the hippocampus and related temporal lobe structures. Hippocampal damage often
      causes severe impairments in the ability to learn and remember a location in
      space defined by distal visual cues. Such cognitive disabilities are found in
      Parkinsonian patients. We recently investigated the role of dopamine in
      navigation in the 6-Hydroxy-dopamine (6-OHDA) rat, a model of Parkinson's disease
      (PD) commonly used to investigate the pathophysiology of dopamine depletion
      (Retailleau et al., 2013). We demonstrated that dopamine (DA) is essential to
      spatial learning as its depletion results in spatial impairments. Our results
      showed that the behavioral effect of DA depletion is correlated with modification
      of the neural encoding of spatial features and decision making processes in
      hippocampus. However, the origin of these alterations in the neural processing of
      the spatial information needs to be clarified. It could result from a local
      effect: dopamine depletion disturbs directly the processing of relevant spatial
      information at hippocampal level. Alternatively, it could result from a more
      distributed network effect: dopamine depletion elsewhere in the brain (entorhinal
      cortex, striatum, etc.) modifies the way hippocampus processes spatial
      information. Recent experimental evidence in rodents, demonstrated indeed, that
      other brain areas are involved in the acquisition of spatial information. Amongst
      these, the cortex-basal ganglia (BG) loop is known to be involved in
      reinforcement learning and has been identified as an important contributor to
      spatial learning. In particular, it has been shown that altered activity of the
      BG striatal complex can impair the ability to perform spatial learning tasks. The
      present review provides a glimpse of the findings obtained over the past decade
      that support a dialog between these two structures during spatial learning under
      DA control. 

PMID- 24672437
TI  - Disrupting neuronal transmission: mechanism of DBS?
AB  - Applying high-frequency stimulation (HFS) to deep brain structure, known as deep
      brain stimulation (DBS), has now been recognized an effective therapeutic option
      for a wide range of neurological and psychiatric disorders. DBS targeting the
      basal ganglia thalamo-cortical loop, especially the internal segment of the
      globus pallidus (GPi), subthalamic nucleus (STN) and thalamus, has been widely
      employed as a successful surgical therapy for movement disorders, such as
      Parkinson's disease, dystonia and tremor. However, the neurophysiological
      mechanism underling the action of DBS remains unclear and is still under debate:
      does DBS inhibit or excite local neuronal elements? In this review, we will
      examine this question and propose the alternative interpretation: DBS dissociates
      inputs and outputs, resulting in disruption of abnormal signal transmission. 

PMID- 24672439
TI  - Augmentation of cognitive brain functions with transcranial lasers.

PMID- 24672438
TI  - Speech perception as an active cognitive process.
AB  - One view of speech perception is that acoustic signals are transformed into
      representations for pattern matching to determine linguistic structure. This
      process can be taken as a statistical pattern-matching problem, assuming
      realtively stable linguistic categories are characterized by neural
      representations related to auditory properties of speech that can be compared to
      speech input. This kind of pattern matching can be termed a passive process which
      implies rigidity of processing with few demands on cognitive processing. An
      alternative view is that speech recognition, even in early stages, is an active
      process in which speech analysis is attentionally guided. Note that this does not
      mean consciously guided but that information-contingent changes in early auditory
      encoding can occur as a function of context and experience. Active processing
      assumes that attention, plasticity, and listening goals are important in
      considering how listeners cope with adverse circumstances that impair hearing by
      masking noise in the environment or hearing loss. Although theories of speech
      perception have begun to incorporate some active processing, they seldom treat
      early speech encoding as plastic and attentionally guided. Recent research has
      suggested that speech perception is the product of both feedforward and feedback
      interactions between a number of brain regions that include descending
      projections perhaps as far downstream as the cochlea. It is important to
      understand how the ambiguity of the speech signal and constraints of context
      dynamically determine cognitive resources recruited during perception including
      focused attention, learning, and working memory. Theories of speech perception
      need to go beyond the current corticocentric approach in order to account for the
      intrinsic dynamics of the auditory encoding of speech. In doing so, this may
      provide new insights into ways in which hearing disorders and loss may be treated
      either through augementation or therapy. 

PMID- 24672440
TI  - Zinc-positive and zinc-negative connections of the claustrum.

PMID- 24672441
TI  - Operant conditioning of spinal reflexes: from basic science to clinical therapy.
AB  - New appreciation of the adaptive capabilities of the nervous system, recent
      recognition that most spinal cord injuries are incomplete, and progress in
      enabling regeneration are generating growing interest in novel rehabilitation
      therapies. Here we review the 35-year evolution of one promising new approach,
      operant conditioning of spinal reflexes. This work began in the late 1970's as
      basic science; its purpose was to develop and exploit a uniquely accessible model
      for studying the acquisition and maintenance of a simple behavior in the
      mammalian central nervous system (CNS). The model was developed first in monkeys
      and then in rats, mice, and humans. Studies with it showed that the ostensibly
      simple behavior (i.e., a larger or smaller reflex) rests on a complex hierarchy
      of brain and spinal cord plasticity; and current investigations are delineating
      this plasticity and its interactions with the plasticity that supports other
      behaviors. In the last decade, the possible therapeutic uses of reflex
      conditioning have come under study, first in rats and then in humans. The initial
      results are very exciting, and they are spurring further studies. At the same
      time, the original basic science purpose and the new clinical purpose are
      enabling and illuminating each other in unexpected ways. The long course and
      current state of this work illustrate the practical importance of basic research
      and the valuable synergy that can develop between basic science questions and
      clinical needs. 

PMID- 24672442
TI  - Endogenous peripheral oxytocin measures can give insight into the dynamics of
      social relationships: a review.
AB  - The neuropeptide, oxytocin, receives increasing attention due to its role in
      stress regulation and promoting affiliative social behavior. Research across
      mammals points to a complex pattern whereby social context and individual
      differences moderate the central release of oxytocin as well as moderate the
      effects that exogenous administration of oxytocin has on social behavior. In
      addition, it is becoming evident that measuring endogenous peripheral oxytocin
      levels is an informative tool. This is particularly so when oxytocin can be
      measured from non-invasively collected samples, such as in urine. Although it is
      still debated as to whether peripheral measures of oxytocin relate to central
      measures of oxytocin, anatomical and functional evidence indicate a link between
      the two. We argue that non-invasive measures of peripheral oxytocin hold several
      research and potential therapeutic advantages. Principally, study subjects can be
      sampled repeatedly in different social contexts where social history between
      interaction partners can be taken into account. Several hormones can be measured
      simultaneously allowing examination of the influence of oxytocin interactions
      with other hormones on motivational states. Valence of relationships as well as
      changes in relationship quality over time can be measured through endocrine
      responses. Also, the approach of identifying natural social contexts that are
      associated with endogenous oxytocin release offers the potential of behavioral
      therapy as an addition or alternative to chemical therapy in the field of mental
      health. 

PMID- 24672443
TI  - A potential role for the paraventricular nucleus of the thalamus in mediating
      individual variation in Pavlovian conditioned responses.
AB  - There is ample evidence to suggest that the paraventricular nucleus of the
      thalamus (PVT) mediates cue-reward learning, especially as it relates to drug
      seeking behavior. However, its exact role in these complex processes remains
      unknown. Here we will present and discuss data from our own laboratory which
      suggests that the PVT plays a role in multiple forms of stimulus-reward learning,
      and does so via distinct neurobiological systems. Using an animal model that
      captures individual variation in response to reward-associated cues, we are able
      to parse the incentive from the predictive properties of reward cues and to
      elucidate the neural circuitry underlying these different forms of cue-reward
      learning. When rats are exposed to a classical Pavlovian conditioning paradigm,
      wherein a cue predicts food reward, some rats, termed sign-trackers, approach and
      manipulate the cue upon its presentation. This behavior is indicative of
      attributing incentive salience to the cue. That is, the cue gains excessive
      control over behavior for sign-trackers. In contrast, other rats, termed goal
      trackers, treat the cue as a mere predictor, and upon its presentation go to the
      location of reward delivery. Based on our own data utilizing this model, we
      hypothesize that the PVT represents a common node, but differentially regulates
      the sign- vs. goal-tracking response. We postulate that the PVT regulates sign
      tracking behavior, or the attribution of incentive salience, via subcortical,
      dopamine-dependent mechanisms. In contrast, we propose that goal-tracking
      behavior, or the attribution of predictive value, is the product of "top-down"
      glutamatergic processing between the prelimbic cortex (PrL) and the PVT.
      Together, data from our laboratory and others support a role for the PVT in cue
      motivated behaviors and suggest that it may be an important locus within the
      neural circuitry that goes awry in addiction and related disorders. 

PMID- 24672444
TI  - Conceptualization of relative size by honeybees.
AB  - The ability to process visual information using relational rules allows for
      decisions independent of the specific physical attributes of individual stimuli.
      Until recently, the manipulation of relational concepts was considered as a
      prerogative of large mammalian brains. Here we show that individual free flying
      honeybees can learn to use size relationship rules to choose either the larger or
      smaller stimulus as the correct solution in a given context, and subsequently
      apply the learnt rule to novel colors and shapes providing that there is
      sufficient input to the long wavelength (green) photoreceptor channel. Our
      results add a novel, size-based conceptual rule to the set of relational concepts
      that honeybees have been shown to master and underline the value of bees as an
      animal model for studying the emergence of conceptualization abilities. 

PMID- 24672445
TI  - Olfactory tubercle stimulation alters odor preference behavior and recruits
      forebrain reward and motivational centers.
AB  - Rodents show robust behavioral responses to odors, including strong preferences
      or aversions for certain odors. The neural mechanisms underlying the effects of
      odors on these behaviors in animals are not well understood. Here, we provide an
      initial proof-of-concept study into the role of the olfactory tubercle (OT), a
      structure with known anatomical connectivity with both brain reward and olfactory
      structures, in regulating odor-motivated behaviors. We implanted c57bl/6 male
      mice with an ipsilateral bipolar electrode into the OT to administer electric
      current and thereby yield gross activation of the OT. We confirmed that
      electrical stimulation of the OT was rewarding, with mice frequently self
      administering stimulation on a fixed ratio schedule. In a separate experiment,
      mice were presented with either fox urine or peanut odors in a three-chamber
      preference test. In absence of OT stimulation, significant preference for the
      peanut odor chamber was observed which was abolished in the presence of OT
      stimulation. Perhaps providing a foundation for this modulation in behavior, we
      found that OT stimulation significantly increased the number of c-Fos positive
      neurons in not only the OT, but also in forebrain structures essential to
      motivated behaviors, including the nucleus accumbens and lateral septum. The
      present results support the notion that the OT is integral to the display of
      motivated behavior and possesses the capacity to modulate odor hedonics either by
      directly altering odor processing or perhaps by indirect actions on brain reward
      and motivation structures. 

PMID- 24672446
TI  - Day and night: diurnal phase influences the response to chronic mild stress.
AB  - Chronic mild stress (CMS) protocols are widely used to create animal models of
      depression. Despite this, the inconsistencies in the reported effects may be
      indicative of crucial differences in methodology. Here, we considered the time of
      the diurnal cycle in which stressors are applied as a possible relevant temporal
      variable underlying the association between stress and behavior. Most
      laboratories test behavior during the light phase of the diurnal cycle, which
      corresponds to the animal's resting period. Here, rats stressed either in their
      resting (light phase) or active (dark phase) periods were behaviorally
      characterized in the light phase. When exposure to CMS occurred during the light
      phase of the day cycle, rats displayed signs of depressive and anxiety-related
      behaviors. This phenotype was not observed when CMS was applied during the dark
      (active) period. Interestingly, although no differences in spatial and reference
      memory were detected (Morris water maze) in animals in either stress period,
      those stressed in the light phase showed marked impairments in the probe test.
      These animals also showed significant dendritic atrophy in the hippocampal
      dentate granule neurons, with a decrease in the number of spines. Taken together,
      the observations reported demonstrate that the time in which stress is applied
      has differential effects on behavioral and neurostructural phenotypes. 

PMID- 24672447
TI  - Linking brain electrical signals elicited by current outcomes with future risk
      decision-making.
AB  - The experience of current outcomes influences future decisions in various ways.
      The neural mechanism of this phenomenon may help to clarify the determinants of
      decision-making. In this study, thirty-nine young adults finished a risky
      gambling task by choosing between a high- and a low-risk option in each trial
      during electroencephalographic data collection. We found that risk-taking
      strategies significantly modulated mean amplitudes of the event-related potential
      (ERP) component P3, particularly at the central scalp. The event-related spectral
      perturbation and the inter-trial coherence measurements of the independent
      component analysis (ICA) data indicated that the "stay" vs. "switch"
      electrophysiological difference associated with subsequent decision-making was
      mainly due to fronto-central theta and left/right mu independent components.
      Event-related cross-coherence results suggested that the neural information of
      action monitoring and updating emerged in the fronto-central cortex and
      propagated to sensorimotor area for further behavior adjustment. Based on these
      findings of ERP and event-related oscillation (ERO) measures, we propose a neural
      model of the influence of current outcomes on future decisions. 

PMID- 24672448
TI  - Neuronal responses to face-like and facial stimuli in the monkey superior
      colliculus.
AB  - The superficial layers of the superior colliculus (sSC) appear to function as a
      subcortical visual pathway that bypasses the striate cortex for the rapid
      processing of coarse facial information. We investigated the responses of neurons
      in the monkey sSC during a delayed non-matching-to-sample (DNMS) task in which
      monkeys were required to discriminate among five categories of visual stimuli
      [photos of faces with different gaze directions, line drawings of faces, face
      like patterns (three dark blobs on a bright oval), eye-like patterns, and simple
      geometric patterns]. Of the 605 sSC neurons recorded, 216 neurons responded to
      the visual stimuli. Among the stimuli, face-like patterns elicited responses with
      the shortest latencies. Low-pass filtering of the images did not influence the
      responses. However, scrambling of the images increased the responses in the late
      phase, and this was consistent with a feedback influence from upstream areas. A
      multidimensional scaling (MDS) analysis of the population data indicated that the
      sSC neurons could separately encode face-like patterns during the first 25-ms
      period after stimulus onset, and stimulus categorization developed in the next
      three 25-ms periods. The amount of stimulus information conveyed by the sSC
      neurons and the number of stimulus-differentiating neurons were consistently
      higher during the 2nd to 4th 25-ms periods than during the first 25-ms period.
      These results suggested that population activity of the sSC neurons
      preferentially filtered face-like patterns with short latencies to allow for the
      rapid processing of coarse facial information and developed categorization of the
      stimuli in later phases through feedback from upstream areas. 

PMID- 24672449
TI  - Ventral striatal dopamine synthesis capacity is associated with individual
      differences in behavioral disinhibition.
AB  - Pathological gambling, alongside addictive and antisocial disorders, forms part
      of a broad psychopathological spectrum of externalizing disorders, which share an
      underlying genetic vulnerability. The shared externalizing propensity is a highly
      heritable, continuously varying trait. Disinhibitory personality traits such as
      impulsivity and novelty seeking (NS) function as indicators of this broad shared
      externalizing tendency, which may reflect, at the neurobiological level,
      variation in the reactivity of dopaminergic (DAergic) brain reward systems
      centered on the ventral striatum (VS). Here, we examined whether individual
      differences in ventral striatal dopamine (DA) synthesis capacity were associated
      with individual variation in disinhibitory personality traits. Twelve healthy
      male volunteers underwent 6-[(18)F]Fluoro-L-DOPA (FDOPA) positron emission
      tomography (PET) scanning to measure striatal DA synthesis capacity, and
      completed a measure of disinhibited personality (NS). We found that levels of
      ventral, but not dorsal, striatal DA synthesis capacity were significantly
      correlated with inter-individual variation in disinhibitory personality traits,
      particularly a propensity for financial extravagance and irresponsibility. Our
      results are consistent with preclinical models of behavioral disinhibition and
      addiction proneness, and provide novel insights into the neurobiology of
      personality based vulnerability to pathological gambling and other externalizing
      disorders. 

PMID- 24672450
TI  - Environmental manipulations generate bidirectional shifts in both behavior and
      gene regulation in a crossbred mouse model of extremes in trait anxiety.
AB  - Although gene-environment interactions are known to significantly influence
      psychopathology-related disease states, only few animal models cover both the
      genetic background and environmental manipulations. Therefore, we have taken
      advantage of the bidirectionally inbred high (HAB) and low (LAB) anxiety-related
      behavior mouse lines to generate HAB * LAB F1 hybrids that intrinsically carry
      both lines' genetic characteristics, and subsequently raised them in three
      different environments-standard, enriched (EE) and chronic mild stress (CMS).
      Assessing genetic correlates of trait anxiety, we focused on two genes already
      known to play a role in HAB vs. LAB mice, corticotropin releasing hormone
      receptor type 1 (Crhr1) and high mobility group nucleosomal binding domain 3
      (Hmgn3). While EE F1 mice showed decreased anxiety-related and increased
      explorative behaviors compared to controls, CMS sparked effects in the opposite
      direction. However, environmental treatments affected the expression of the two
      genes in distinct ways. Thus, while expression ratios of Hmgn3 between the HAB-
      and LAB-specific alleles remained equal, total expression resembled the one
      observed in HAB vs. LAB mice, i.e., decreased after EE and increased after CMS
      treatment. On the other hand, while total expression of Crhr1 remained unchanged
      between the groups, the relative expression of HAB- and LAB-specific alleles
      showed a clear effect following the environmental modifications. Thus, the
      environmentally driven bidirectional shift of trait anxiety in this F1 model
      strongly correlated with Hmgn3 expression, irrespective of allele-specific
      expression patterns that retained the proportions of basic differential HAB vs.
      LAB expression, making this gene a match for environment-induced modifications.
      An involvement of Crhr1 in the bidirectional behavioral shift could, however,
      rather be due to different effects of the HAB- and LAB-specific alleles described
      here. Both candidate genes therefore deserve attention in the complex regulation
      of anxiety-related phenotypes including environment-mediated effects. 

PMID- 24672451
TI  - Structural hippocampal anomalies in a schizophrenia population correlate with
      navigation performance on a wayfinding task.
AB  - Episodic memory, related to the hippocampus, has been found to be impaired in
      schizophrenia. Further, hippocampal anomalies have also been observed in
      schizophrenia. This study investigated whether average hippocampal gray matter
      (GM) would differentiate performance on a hippocampus-dependent memory task in
      patients with schizophrenia and healthy controls. Twenty-one patients with
      schizophrenia and 22 control participants were scanned with an MRI while being
      tested on a wayfinding task in a virtual town (e.g., find the grocery store from
      the school). Regressions were performed for both groups individually and together
      using GM and performance on the wayfinding task. Results indicate that controls
      successfully completed the task more often than patients, took less time, and
      made fewer errors. Additionally, controls had significantly more hippocampal GM
      than patients. Poor performance was associated with a GM decrease in the right
      hippocampus for both groups. Within group regressions found an association
      between right hippocampi GM and performance in controls and an association
      between the left hippocampi GM and performance in patients. A second analysis
      revealed that different anatomical GM regions, known to be associated with the
      hippocampus, such as the parahippocampal cortex, amygdala, medial, and orbital
      prefrontal cortices, covaried with the hippocampus in the control group.
      Interestingly, the cuneus and cingulate gyrus also covaried with the hippocampus
      in the patient group but the orbital frontal cortex did not, supporting the
      hypothesis of impaired connectivity between the hippocampus and the frontal
      cortex in schizophrenia. These results present important implications for
      creating intervention programs aimed at measuring functional and structural
      changes in the hippocampus in schizophrenia. 

PMID- 24672452
TI  - Neural correlates of spatial navigation changes in mild cognitive impairment and
      Alzheimer's disease.
AB  - Although the memory impairment is a hallmark of Alzheimer's disease (AD), AD has
      also been characterized by spatial disorientation, which is present from its
      early stages. Spatial disorientation in AD manifests itself in getting lost in
      familiar and unfamiliar places and have been characterized more specifically
      using spatial navigation tests in both real space and virtual environments as an
      impairment in multiple spatial abilities, including allocentric and egocentric
      navigation strategies, visuo-spatial perception, or selection of relevant
      information for successful navigation. Patients suffering mild cognitive
      impairment (MCI), who are at a high risk of development of dementia, show
      impairment in a subset of these abilities, mainly connected with allocentric and
      egocentric processing. While spatial disorientation in typical AD patients
      probably reflects neurodegenerative changes in medial and posterior temporal,
      parietal, and frontal lobes, and retrosplenial cortex, the impairment of spatial
      navigation in MCI seem to be connected mainly with the medial temporal and also
      parietal brain changes. In this review, we will summarize the signs of brain
      disease in most MCI and AD patients showing in various tasks of spatial memory
      and navigation. 

PMID- 24672453
TI  - Nogo-A-deficient Transgenic Rats Show Deficits in Higher Cognitive Functions,
      Decreased Anxiety, and Altered Circadian Activity Patterns.
AB  - Decreased levels of Nogo-A-dependent signaling have been shown to affect behavior
      and cognitive functions. In Nogo-A knockout and knockdown laboratory rodents,
      behavioral alterations were observed, possibly corresponding with human
      neuropsychiatric diseases of neurodevelopmental origin, particularly
      schizophrenia. This study offers further insight into behavioral manifestations
      of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial
      cognition, anxiety levels, circadian rhythmicity, and activity patterns.
      Demonstrated is an impairment of cognitive functions and behavioral flexibility
      in a spatial active avoidance task, while non-spatial memory in a step-through
      avoidance task was spared. No signs of anhedonia, typical for schizophrenic
      patients, were observed in the animals. Some measures indicated lower anxiety
      levels in the Nogo-A-deficient group. Circadian rhythmicity in locomotor activity
      was preserved in the Nogo-A knockout rats and their circadian period (tau) did
      not differ from controls. However, daily activity patterns were slightly altered
      in the knockdown animals. We conclude that a reduction of Nogo-A levels induces
      changes in CNS development, manifested as subtle alterations in cognitive
      functions, emotionality, and activity patterns. 

PMID- 24672454
TI  - A phosphodiesterase 4-controlled switch between memory extinction and
      strengthening in the hippocampus.
AB  - Established fear-related memories can undergo phenomena such as extinction or
      reconsolidation when recalled. Extinction probably involves the creation of a
      new, competing memory trace that decreases fear expression, whereas
      reconsolidation can mediate memory maintenance, updating, or strengthening. The
      factors determining whether retrieval will initiate extinction, reconsolidation,
      or neither of these two processes include training intensity, duration of the
      retrieval session, and age of the memory. However, previous studies have not
      shown that the same behavioral protocol can be used to induce either extinction
      or reconsolidation and strengthening, depending on the pharmacological
      intervention used. Here we show that, within an experiment that leads to
      extinction in control rats, memory can be strengthened if rolipram, a selective
      inhibitor of phosphodiesterase type 4 (PDE4), is administered into the dorsal
      hippocampus immediately after retrieval. The memory-enhancing effect of rolipram
      lasted for at least 1 week, was blocked by the protein synthesis inhibitor
      anisomycin, and did not occur when drug administration was not paired with
      retrieval. These findings indicate that the behavioral outcome of memory
      retrieval can be pharmacologically switched from extinction to strengthening. The
      cAMP/protein kinase A (PKA) signaling pathway might be a crucial mechanism
      determining the fate of memories after recall. 

PMID- 24672455
TI  - T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired
      memory and reduced sensitivity to psychostimulants.
AB  - The fine-tuning of neuronal excitability relies on a tight control of Ca(2+)
      homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1,
      Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes.
      Despite their wide expression throughout the central nervous system, the
      implication of T-type Cav3.2 isoform in brain functions is still poorly
      characterized. Here, we investigate the effect of genetic ablation of this
      isoform in affective disorders, including anxiety, cognitive functions as well as
      sensitivity to drugs of abuse. Using a wide range of behavioral assays we show
      that genetic ablation of the cacna1h gene results in an anxiety-like phenotype,
      whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type
      channel Cav3.2 also triggers impairment of hippocampus-dependent recognition
      memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and
      cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition,
      the administration of the T-type blocker TTA-A2 prevented the expression of
      locomotor sensitization observed in wildtype mice. In conclusion, our data reveal
      that physiological activity of this specific Ca(2+) channel is required for
      affective and cognitive behaviors. Moreover, our work highlights the interest of
      T-type channel blockers as therapeutic strategies to reverse drug-associated
      alterations. 

PMID- 24672456
TI  - Learned EEG-based brain self-regulation of motor-related oscillations during
      application of transcranial electric brain stimulation: feasibility and
      limitations.
AB  - OBJECTIVE: Transcranial direct current stimulation (tDCS) improves motor learning
      and can affect emotional processing and attention. However, it is unclear whether
      learned electroencephalography (EEG)-based brain-machine interface (BMI) control
      during tDCS is feasible, how application of transcranial electric currents during
      BMI control would interfere with feature-extraction of physiological brain
      signals and how it affects brain control performance. Here we tested this
      combination and evaluated stimulation-dependent artifacts across different EEG
      frequencies and stability of motor imagery-based BMI control. APPROACH: Ten
      healthy volunteers were invited to two BMI-sessions, each comprising two 60-trial
      blocks. During the trials, learned desynchronization of mu-rhythms (8-15 Hz)
      associated with motor imagery (MI) recorded over C4 was translated into online
      cursor movements on a computer screen. During block 2, either sham (session A) or
      anodal tDCS (session B) was applied at 1 mA with the stimulation electrode placed
      1 cm anterior of C4. MAIN RESULTS: tDCS was associated with a significant signal
      power increase in the lower frequencies most evident in the signal spectrum of
      the EEG channel closest to the stimulation electrode. Stimulation-dependent
      signal power increase exhibited a decay of 12 dB per decade, leaving frequencies
      above 9 Hz unaffected. Analysis of BMI control performance did not indicate a
      difference between blocks and tDCS conditions. CONCLUSION: Application of tDCS
      during learned EEG-based self-regulation of brain oscillations above 9 Hz is
      feasible and safe, and might improve applicability of BMI systems.

PMID- 24672457
TI  - Evolutionary appearance of von Economo's neurons in the mammalian cerebral
      cortex.
AB  - von Economo's neurons (VENs) are large, spindle-shaped projection neurons in
      layer V of the frontoinsular (FI) cortex, and the anterior cingulate cortex.
      During human ontogenesis, the VENs can first be differentiated at late stages of
      gestation, and increase in number during the first eight postnatal months. VENs
      have been identified in humans, chimpanzee, bonobos, gorillas, orangutan and,
      more recently, in the macaque. Their distribution in great apes seems to
      correlate with human-like social cognitive abilities and self-awareness. VENs are
      also found in whales, in a number of different cetaceans, and in the elephant.
      This phylogenetic distribution may suggest a correlation among the VENs, brain
      size and the "social brain." VENs may be involved in the pathogenesis of specific
      neurological and psychiatric diseases, such as autism, callosal agenesis and
      schizophrenia. VENs are selectively affected in a behavioral variant of
      frontotemporal dementia in which empathy, social awareness and self-control are
      seriously compromised, thus associating VENs with the social brain. However, the
      presence of VENs has also been related to special functions such as mirror self
      recognition. Areas containing VENs have been related to motor awareness or sense
      of-knowing, discrimination between self and other, and between self and the
      external environment. Along this line, VENs have been related to the "global
      Workspace" architecture: in accordance the VENs have been correlated to emotional
      and interoceptive signals by providing fast connections (large axons = fast
      communication) between salience-related insular and cingulate and other widely
      separated brain areas. Nevertheless, the lack of a characterization of their
      physiology and anatomical connectivity allowed only to infer their functional
      role based on their location and on the functional magnetic resonance imaging
      data. The recent finding of VENs in the anterior insula of the macaque opens the
      way to new insights and experimental investigations. 

PMID- 24672458
TI  - Self-generated thoughts and depression: from daydreaming to depressive symptoms.
AB  - Human minds often engage in thoughts and feelings that are self-generated rather
      than stimulus-dependent, such as daydreaming. Recent research suggests that under
      certain circumstances, daydreaming is associated with adverse effects on
      cognition and affect. Based on recent literature about the influence of resting
      mind in relation to rumination and depression, this questionnaire study
      investigated mechanisms linking daydreaming to depressive symptoms. Specifically,
      an indirect effect model was tested in which daydreaming influences depressive
      symptoms through enhancing self-focus and ruminative thought. Results were in
      line with the hypothesis and several alternative pathways were ruled out. The
      results provide initial supportive evidence that daydreaming can influence
      depressive symptoms through influences on self-focus and rumination. Further
      research should use prospective or experimental designs to further validate and
      strengthen these conclusions. 

PMID- 24672459
TI  - Allocentric directional processing in the rodent and human retrosplenial cortex.
AB  - Head direction (HD) cells in the rodent brain have been investigated for a number
      of years, providing us with a detailed understanding of how the rodent brain
      codes for allocentric direction. Allocentric direction refers to the orientation
      of the external environment, independent of one's current (egocentric)
      orientation. The presence of neural activity related to allocentric directional
      coding in humans has also been noted but only recently directly tested. Given the
      current status of both fields, it seems beneficial to draw parallels between this
      rodent and human research. We therefore discuss how findings from the human
      retrosplenial cortex (RSC), including its "translational function" (converting
      egocentric to allocentric information) and ability to code for permanent objects,
      compare to findings from the rodent RSC. We conclude by suggesting critical
      future experiments that derive from a cross-species approach to understanding the
      function of the human RSC. 

PMID- 24672460
TI  - Bodily self and immune self: is there a link?

PMID- 24672461
TI  - The role of action representations in thematic object relations.
AB  - A number of studies have explored the role of associative/event-based (thematic)
      and categorical (taxonomic) relations in the organization of object
      representations. Recent evidence suggests that thematic information may be
      particularly important in determining relationships between manipulable
      artifacts. However, although sensorimotor information is on many accounts an
      important component of manipulable artifact representations, little is known
      about the role that action may play during the processing of semantic
      relationships (particularly thematic relationships) between multiple objects. In
      this study, we assessed healthy and left hemisphere stroke participants to
      explore three questions relevant to object relationship processing. First, we
      assessed whether participants tended to favor thematic relations including action
      (Th+A, e.g., wine bottle-corkscrew), thematic relationships without action (Th-A,
      e.g., wine bottle-cheese), or taxonomic relationships (Tax, e.g., wine bottle
      water bottle) when choosing between them in an association judgment task with
      manipulable artifacts. Second, we assessed whether the underlying constructs of
      event relatedness, action relatedness, and categorical relatedness determined the
      choices that participants made. Third, we assessed the hypothesis that degraded
      action knowledge and/or damage to temporo-parietal cortex, a region of the brain
      associated with the representation of action knowledge, would reduce the
      influence of action on the choice task. Experiment 1 showed that explicit ratings
      of event, action, and categorical relatedness were differentially predictive of
      healthy participants' choices, with action relatedness determining choices
      between Th+A and Th-A associations above and beyond event and categorical
      ratings. Experiment 2 focused more specifically on these Th+A vs. Th-A choices
      and demonstrated that participants with left temporo-parietal lesions, a brain
      region known to be involved in sensorimotor processing, were less likely than
      controls and tended to be less likely than patients with lesions sparing that
      region to use action relatedness in determining their choices. These data
      indicate that action knowledge plays a critical role in processing of thematic
      relations for manipulable artifacts. 

PMID- 24672462
TI  - Knowledge of facts mediate "continuous improvement" in elite sport: a comment on
      Stanley and Krakauer (2013).

PMID- 24672463
TI  - Being "in" or "out" of the game: subjective and acoustic reactions to exclusion
      and popularity in social anxiety.
AB  - Social Anxiety (SA) has been shown to be associated with compensatory deficits in
      pro-social behavior following exclusion and with failure to capitalize on social
      success. We assessed the subjective and expressive responses of high (n = 48) and
      low (n = 56) socially anxious individuals to exclusion, acceptance, and
      popularity induced by a participation in an online ball-tossing game. Before the
      manipulation, participants read aloud neutral and command utterances. Following
      the manipulation, participants rated their mood and cognitions and re-read the
      utterances. Acoustic properties (fundamental frequency-mF0, vocal intensity) of
      these utterances were analyzed. We found greater differences in self-esteem
      between high and low socially anxious individuals following the exclusion
      condition, as compared to the acceptance condition. Among low socially anxious
      individuals, exclusion promoted increased vocal confidence, as indicated by
      decreased mF0 and increased vocal intensity in uttering commands; High socially
      anxious individuals exhibited an opposite reaction, responding to exclusion by
      decreased vocal confidence. Following popularity, high SA was associated with
      decreased enhancement in mood and self-esteem in women but not in men. Consistent
      with evolutionary and interpersonal accounts of SA, we highlight the importance
      of examining the effects of SA and gender on events indicating unambiguous and
      unanimous social acceptance. Examining reactivity to changes in belongingness may
      have important implications for understanding the core mechanisms of SA. 

PMID- 24672464
TI  - Intralimb coordination as a sensitive indicator of motor-control impairment after
      spinal cord injury.
AB  - BACKGROUND: Recovery of walking function after neurotrauma, e.g., after spinal
      cord injury, is routinely captured using standardized walking outcome measures of
      time and distance. However, these measures do not provide information on possible
      underlying mechanisms of recovery, nor do they tell anything about the quality of
      gait. Subjects with an incomplete spinal cord injury are a very heterogeneous
      group of people with a wide range of functional impairments. A stratification of
      these subjects would allow increasing sensitivity for hypothesis testing and a
      more targeted treatment strategy. METHODS: The gait of incomplete spinal cord
      injured subjects was compared to healthy control subjects by analyzing kinematic
      data obtained by a 3-D motion capture system. Hip-knee angle-angle plots
      (cyclograms) informed on the qualitative aspect of gait and the intralimb
      coordination. Features of the cyclogram, e.g., shape of the cyclogram, cycle-to
      cycle consistency and its modulation due to changes in walking speed were
      discerned and used to stratify spinal cord injured subjects. RESULTS: Spinal cord
      injured subjects were unable to modulate their cyclogram configuration when
      increasing speed from slow to preferred. Their gait quality remained clearly
      aberrant and showed even higher deviations from normal when walking at preferred
      speed. Qualitative categorization of spinal cord injured subjects based on their
      intralimb coordination was complemented by quantitative measures of cyclogram
      shape comparison. DISCUSSION: Spinal cord injured subjects showed distinct
      distortions of intralimb coordination as well as limited modulation to changes in
      walking speed. The specific changes of the cyclograms revealed complementary
      insight in the disturbance of lower-limb control in addition to measures of time
      and distance and may be a useful tool for patient categorization and
      stratification prior to clinical trial inclusion.

PMID- 24672465
TI  - Development of the transcallosal motor fiber from the corticospinal tract in the
      human brain: diffusion tensor imaging study.
AB  - Transcallosal motor fiber (TCMF) plays a role in interhemispheric inhibition
      (IHI) between two primary motor cortices. IHI has been an important concept in
      development of the motor system of the brain. Many studies have focused on the
      research of the topography of TCMF, however, little is known about development of
      TCMF. In the current study, we attempted to investigate development of TCMF from
      the corticospinal tract (CST) in the human brain using diffusion tensor
      tractography. A total of 76 healthy subjects were recruited for this study. We
      reconstructed the TCMF, which was derived from the CST, by selection of two
      regions of interest below the corpus callosum (upper and middle pons).
      Termination criteria used for fiber tracking were fractional anisotropy <0.2 and
      three tract turning angles of <45, 60, and 75( degrees ). The subjects were
      classified into four groups according to age: group A (0-5 years), group B (6-10
      years), group C (11-15 years), and group D (16-20 years). Significant differences
      in the incidence of TCMF were observed between group B and group C, and between
      group B and group D, with tract turning angles of 60 and 75( degrees ) (p <
      0.05). However, no significant differences in any tract turning angle were
      observed between group C and group D (p > 0.05). In addition, in terms of the
      incidence of TCMF, no significant differences were observed between the three
      tract turning angles (p > 0.05). We obtained visualized TCMF from the CST with
      development and found that the incidence of TCMF differed significantly around
      the approximate age of 10 years. As a result, we demonstrated structural evidence
      for development of TCMF in the human brain. 

PMID- 24672466
TI  - Retro-priming, priming, and double testing: psi and replication in a test-retest
      design.
AB  - Numerous experiments have been conducted in recent years on anomalous retroactive
      influences on cognition and affect (Bem, 2010), yet more data are needed to
      understand these processes precisely. For this purpose, we carried out an initial
      retro-priming study in which the response times of 162 participants were measured
      (Rabeyron and Watt, 2010). In the current paper, we present the results of a
      second study in which we selected those participants who demonstrated the
      strongest retro-priming effect during the first study, in order to see if we
      could replicate this effect and therefore select high scoring participants. An
      additional objective was to try to find correlations between psychological
      characteristics (anomalous experiences, mental health, mental boundaries, trauma,
      negative life events) and retro-priming results for the high scoring
      participants. The retro-priming effect was also compared with performance on a
      classical priming task. Twenty-eight participants returned to the laboratory for
      this new study. The results, for the whole group, on the retro-priming task, were
      negative and non-significant (es = -0.25, ns) and the results were significant on
      the priming task (es = 0.63, p < 0.1). We obtained overall negative effects on
      retro-priming results for all the sub-groups (students, male, female). Ten
      participants were found to have positive results on the two retro-priming
      studies, but no specific psychological variables were found for these
      participants compared to the others. Several hypotheses are considered in
      explaining these results, and the author provide some final thoughts concerning
      psi and replicability. 

PMID- 24672467
TI  - Reading the Freudian theory of sexual drives from a functional neuroimaging
      perspective.
AB  - One of the essential tasks of neuropsychoanalysis is to investigate the neural
      correlates of sexual drives. Here, we consider the four defining characteristics
      of sexual drives as delineated by Freud: their pressure, aim, object, and source.
      We systematically examine the relations between these characteristics and the
      four-component neurophenomenological model that we have proposed based on
      functional neuroimaging studies, which comprises a cognitive, a motivational, an
      emotional and an autonomic/neuroendocrine component. Functional neuroimaging
      studies of sexual arousal (SA) have thrown a new light on the four fundamental
      characteristics of sexual drives by identifying their potential neural
      correlates. While these studies are essentially consistent with the Freudian
      model of drives, the main difference emerging between the functional neuroimaging
      perspective on sexual drives and the Freudian theory relates to the source of
      drives. From a functional neuroimaging perspective, sources of sexual drives,
      conceived by psychoanalysis as processes of excitation occurring in a peripheral
      organ, do not seem, at least in adult subjects, to be an essential part of the
      determinants of SA. It is rather the central processing of visual or genital
      stimuli that gives to these stimuli their sexually arousing and sexually
      pleasurable character. Finally, based on functional neuroimaging results, some
      possible improvements to the psychoanalytic theory of sexual drives are
      suggested. 

PMID- 24672469
TI  - Chunking dynamics: heteroclinics in mind.
AB  - Recent results of imaging technologies and non-linear dynamics make possible to
      relate the structure and dynamics of functional brain networks to different
      mental tasks and to build theoretical models for the description and prediction
      of cognitive activity. Such models are non-linear dynamical descriptions of the
      interaction of the core components-brain modes-participating in a specific mental
      function. The dynamical images of different mental processes depend on their
      temporal features. The dynamics of many cognitive functions are transient. They
      are often observed as a chain of sequentially changing metastable states. A
      stable heteroclinic channel (SHC) consisting of a chain of saddles-metastable
      states-connected by unstable separatrices is a mathematical image for robust
      transients. In this paper we focus on hierarchical chunking dynamics that can
      represent several forms of transient cognitive activity. Chunking is a dynamical
      phenomenon that nature uses to perform information processing of long sequences
      by dividing them in shorter information items. Chunking, for example, makes more
      efficient the use of short-term memory by breaking up long strings of information
      (like in language where one can see the separation of a novel on chapters,
      paragraphs, sentences, and finally words). Chunking is important in many
      processes of perception, learning, and cognition in humans and animals. Based on
      anatomical information about the hierarchical organization of functional brain
      networks, we propose a cognitive network architecture that hierarchically chunks
      and super-chunks switching sequences of metastable states produced by winnerless
      competitive heteroclinic dynamics. 

PMID- 24672470
TI  - CyNEST: a maintainable Cython-based interface for the NEST simulator.
AB  - NEST is a simulator for large-scale networks of spiking point neuron models
      (Gewaltig and Diesmann, 2007). Originally, simulations were controlled via the
      Simulation Language Interpreter (SLI), a built-in scripting facility implementing
      a language derived from PostScript (Adobe Systems, Inc., 1999). The introduction
      of PyNEST (Eppler et al., 2008), the Python interface for NEST, enabled users to
      control simulations using Python. As the majority of NEST users found PyNEST
      easier to use and to combine with other applications, it immediately displaced
      SLI as the default NEST interface. However, developing and maintaining PyNEST has
      become increasingly difficult over time. This is partly because adding new
      features requires writing low-level C++ code intermixed with calls to the
      Python/C API, which is unrewarding. Moreover, the Python/C API evolves with each
      new version of Python, which results in a proliferation of version-dependent code
      branches. In this contribution we present the re-implementation of PyNEST in the
      Cython language, a superset of Python that additionally supports the declaration
      of C/C++ types for variables and class attributes, and provides a convenient
      foreign function interface (FFI) for invoking C/C++ routines (Behnel et al.,
      2011). Code generation via Cython allows the production of smaller and more
      maintainable bindings, including increased compatibility with all supported
      Python releases without additional burden for NEST developers. Furthermore, this
      novel approach opens up the possibility to support alternative implementations of
      the Python language at no cost given a functional Cython back-end for the
      corresponding implementation, and also enables cross-compilation of Python
      bindings for embedded systems and supercomputers alike. 

PMID- 24672468
TI  - Development of Human Somatosensory Cortical Functions - What have We Learned from
      Magnetoencephalography: A Review.
AB  - The mysteries of early development of cortical processing in humans have started
      to unravel with the help of new non-invasive brain research tools like
      multichannel magnetoencephalography (MEG). In this review, we evaluate, within a
      wider neuroscientific and clinical context, the value of MEG in studying normal
      and disturbed functional development of the human somatosensory system. The
      combination of excellent temporal resolution and good localization accuracy
      provided by MEG has, in the case of somatosensory studies, enabled the
      differentiation of activation patterns from the newborn's primary (SI) and
      secondary somatosensory (SII) areas. Furthermore, MEG has shown that the
      functioning of both SI and SII in newborns has particular immature features in
      comparison with adults. In extremely preterm infants, the neonatal MEG response
      from SII also seems to potentially predict developmental outcome: those lacking
      SII responses at term show worse motor performance at age 2 years than those with
      normal SII responses at term. In older children with unilateral early brain
      lesions, bilateral alterations in somatosensory cortical activation detected in
      MEG imply that the impact of a localized insult may have an unexpectedly wide
      effect on cortical somatosensory networks. The achievements over the last decade
      show that MEG provides a unique approach for studying the development of the
      somatosensory system and its disturbances in childhood. MEG well complements
      other neuroimaging methods in studies of cortical processes in the developing
      brain. 

PMID- 24672471
TI  - BROCCOLI: Software for fast fMRI analysis on many-core CPUs and GPUs.
AB  - Analysis of functional magnetic resonance imaging (fMRI) data is becoming ever
      more computationally demanding as temporal and spatial resolutions improve, and
      large, publicly available data sets proliferate. Moreover, methodological
      improvements in the neuroimaging pipeline, such as non-linear spatial
      normalization, non-parametric permutation tests and Bayesian Markov Chain Monte
      Carlo approaches, can dramatically increase the computational burden. Despite
      these challenges, there do not yet exist any fMRI software packages which
      leverage inexpensive and powerful graphics processing units (GPUs) to perform
      these analyses. Here, we therefore present BROCCOLI, a free software package
      written in OpenCL (Open Computing Language) that can be used for parallel
      analysis of fMRI data on a large variety of hardware configurations. BROCCOLI
      has, for example, been tested with an Intel CPU, an Nvidia GPU, and an AMD GPU.
      These tests show that parallel processing of fMRI data can lead to significantly
      faster analysis pipelines. This speedup can be achieved on relatively standard
      hardware, but further, dramatic speed improvements require only a modest
      investment in GPU hardware. BROCCOLI (running on a GPU) can perform non-linear
      spatial normalization to a 1 mm(3) brain template in 4-6 s, and run a second
      level permutation test with 10,000 permutations in about a minute. These non
      parametric tests are generally more robust than their parametric counterparts,
      and can also enable more sophisticated analyses by estimating complicated null
      distributions. Additionally, BROCCOLI includes support for Bayesian first-level
      fMRI analysis using a Gibbs sampler. The new software is freely available under
      GNU GPL3 and can be downloaded from github
      (https://github.com/wanderine/BROCCOLI/). 

PMID- 24672472
TI  - Polarity-specific high-level information propagation in neural networks.
AB  - Analyzing the connectome of a nervous system provides valuable information about
      the functions of its subsystems. Although much has been learned about the
      architectures of neural networks in various organisms by applying analytical
      tools developed for general networks, two distinct and functionally important
      properties of neural networks are often overlooked. First, neural networks are
      endowed with polarity at the circuit level: Information enters a neural network
      at input neurons, propagates through interneurons, and leaves via output neurons.
      Second, many functions of nervous systems are implemented by signal propagation
      through high-level pathways involving multiple and often recurrent connections
      rather than by the shortest paths between nodes. In the present study, we
      analyzed two neural networks: the somatic nervous system of Caenorhabditis
      elegans (C. elegans) and the partial central complex network of Drosophila, in
      light of these properties. Specifically, we quantified high-level propagation in
      the vertical and horizontal directions: the former characterizes how signals
      propagate from specific input nodes to specific output nodes and the latter
      characterizes how a signal from a specific input node is shared by all output
      nodes. We found that the two neural networks are characterized by very efficient
      vertical and horizontal propagation. In comparison, classic small-world networks
      show a trade-off between vertical and horizontal propagation; increasing the
      rewiring probability improves the efficiency of horizontal propagation but
      worsens the efficiency of vertical propagation. Our result provides insights into
      how the complex functions of natural neural networks may arise from a design that
      allows them to efficiently transform and combine input signals. 

PMID- 24672473
TI  - Ongoing behavior predicts perceptual report of interval duration.
AB  - The ability to estimate the passage of time is essential for adaptive behavior in
      complex environments. Yet, it is not known how the brain encodes time over the
      durations necessary to explain animal behavior. Under temporally structured
      reinforcement schedules, animals tend to develop temporally structured behavior,
      and interval timing has been suggested to be accomplished by learning sequences
      of behavioral states. If this is true, trial to trial fluctuations in behavioral
      sequences should be predictive of fluctuations in time estimation. We trained
      rodents in an duration categorization task while continuously monitoring their
      behavior with a high speed camera. Animals developed highly reproducible
      behavioral sequences during the interval being timed. Moreover, those sequences
      were often predictive of perceptual report from early in the trial, providing
      support to the idea that animals may use learned behavioral patterns to estimate
      the duration of time intervals. To better resolve the issue, we propose that
      continuous and simultaneous behavioral and neural monitoring will enable
      identification of neural activity related to time perception that is not
      explained by ongoing behavior. 

PMID- 24672474
TI  - Everyday robotic action: lessons from human action control.
AB  - Robots are increasingly capable of performing everyday human activities such as
      cooking, cleaning, and doing the laundry. This requires the real-time planning
      and execution of complex, temporally extended sequential actions under high
      degrees of uncertainty, which provides many challenges to traditional approaches
      to robot action control. We argue that important lessons in this respect can be
      learned from research on human action control. We provide a brief overview of
      available psychological insights into this issue and focus on four principles
      that we think could be particularly beneficial for robot control: the integration
      of symbolic and subsymbolic planning of action sequences, the integration of
      feedforward and feedback control, the clustering of complex actions into
      subcomponents, and the contextualization of action-control structures through
      goal representations. 

PMID- 24672475
TI  - Intensive Measurement Designs for Research on Aging.
AB  - Intensive measurement burst designs permit analysis of behavioral and biological
      processes as they unfold over short and long periods of time and providing the
      opportunity to identify change from an individual's normative level of
      functioning. The measurement burst design permits statistical decomposition of
      short-term variation and learning effects that overlay normative aging and
      provide stronger bases for detecting accelerated change due to pathological
      processes. We provide an overview of design features and analysis of measurement
      burst data in Project MIND. The objective of intensive measurement designs is to
      obtain greater resolution of processes of interest that permit reliable and
      sensitive assessments of functioning and change in functioning and of key
      determinants underlying short-term variation and long-term aging and health
      related change.

PMID- 24672478
TI  - Stuck in the mud: time for change in the implementation of cognitive training
      research in ageing?

PMID- 24672477
TI  - Targeting multiple pathogenic mechanisms with polyphenols for the treatment of
      Alzheimer's disease-experimental approach and therapeutic implications.
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging
      and currently has no cure. Its onset and progression are influenced by multiple
      factors. There is growing consensus that successful treatment will rely on
      simultaneously targeting multiple pathological features of AD. Polyphenol
      compounds have many proven health benefits. In this study, we tested the
      hypothesis that combining three polyphenolic preparations (grape seed extract,
      resveratrol, and Concord grape juice extract), with different polyphenolic
      compositions and partially redundant bioactivities, may simultaneously and
      synergistically mitigate amyloid-beta (Abeta) mediated neuropathology and
      cognitive impairments in a mouse model of AD. We found that administration of the
      polyphenols in combination did not alter the profile of bioactive polyphenol
      metabolites in the brain. We also found that combination treatment resulted in
      better protection against cognitive impairments compared to individual
      treatments, in J20 AD mice. Electrophysiological examination showed that acute
      treatment with select brain penetrating polyphenol metabolites, derived from
      these polyphenols, improved oligomeric Abeta (oAbeta)-induced long term
      potentiation (LTP) deficits in hippocampal slices. Moreover, we found greatly
      reduced total amyloid content in the brain following combination treatment. Our
      studies provided experimental evidence that application of polyphenols targeting
      multiple disease-mechanisms may yield a greater likelihood of therapeutic
      efficacy. 

PMID- 24672480
TI  - The many questions on the use of biomarkers for neurodegenerative diseases in
      clinical practice.

PMID- 24672479
TI  - Transcriptomics of post-stroke angiogenesis in the aged brain.
AB  - Despite the obvious clinical significance of post-stroke angiogenesis in aged
      subjects, a detailed transcriptomic analysis of post-stroke angiogenesis has not
      yet been undertaken in an aged experimental model. In this study, by combining
      stroke transcriptomics with immunohistochemistry in aged rats and post-stroke
      patients, we sought to identify an age-specific gene expression pattern that may
      characterize the angiogenic process after stroke. We found that both young and
      old infarcted rats initiated vigorous angiogenesis. However, the young rats had a
      higher vascular density by day 14 post-stroke. "New-for-stroke" genes that were
      linked to the increased vasculature density in young animals included Angpt2,
      Angptl2, Angptl4, Cib1, Ccr2, Col4a2, Cxcl1, Lef1, Hhex, Lamc1, Nid2, Pcam1,
      Plod2, Runx3, Scpep1, S100a4, Tgfbi, and Wnt4, which are required for sprouting
      angiogenesis, reconstruction of the basal lamina (BL), and the resolution phase.
      The vast majority of genes involved in sprouting angiogenesis (Angpt2, Angptl4,
      Cib1, Col8a1, Nrp1, Pcam1, Pttg1ip, Rac2, Runx1, Tnp4, Wnt4); reconstruction of a
      new BL (Col4a2, Lamc1, Plod2); or tube formation and maturation (Angpt1, Gpc3,
      Igfbp7, Sparc, Tie2, Tnfsf10), had however, a delayed upregulation in the aged
      rats. The angiogenic response in aged rats was further diminished by the
      persistent upregulation of "inflammatory" genes (Cxcl12, Mmp8, Mmp12, Mmp14,
      Mpeg1, Tnfrsf1a, Tnfrsf1b) and vigorous expression of genes required for the
      buildup of the fibrotic scar (Cthrc1, Il6ra, Il13ar1, Il18, Mmp2, Rassf4, Tgfb1,
      Tgfbr2, Timp1). Beyond this barrier, angiogenesis in the aged brains was similar
      to that in young brains. We also found that the aged human brain is capable of
      mounting a vigorous angiogenic response after stroke, which most likely reflects
      the remaining brain plasticity of the aged brain. 

PMID- 24672476
TI  - The best-laid plans go oft awry: synaptogenic growth factor signaling in
      neuropsychiatric disease.
AB  - Growth factors play important roles in synapse formation. Mouse models of
      neuropsychiatric diseases suggest that defects in synaptogenic growth factors,
      their receptors, and signaling pathways can lead to disordered neural development
      and various behavioral phenotypes, including anxiety, memory problems, and social
      deficits. Genetic association studies in humans have found evidence for similar
      relationships between growth factor signaling pathways and neuropsychiatric
      phenotypes. Accumulating data suggest that dysfunction in neuronal circuitry,
      caused by defects in growth factor-mediated synapse formation, contributes to the
      susceptibility to multiple neuropsychiatric diseases, including epilepsy, autism,
      and disorders of thought and mood (e.g., schizophrenia and bipolar disorder,
      respectively). In this review, we will focus on how specific synaptogenic growth
      factors and their downstream signaling pathways might be involved in the
      development of neuropsychiatric diseases. 

PMID- 24672481
TI  - Neuroimaging explanations of age-related differences in task performance.
AB  - Advancing age affects both cognitive performance and functional brain activity
      and interpretation of these effects has led to a variety of conceptual research
      models without always explicitly linking the two effects. However, to best
      understand the multifaceted effects of advancing age, age differences in
      functional brain activity need to be explicitly tied to the cognitive task
      performance. This work hypothesized that age-related differences in task
      performance are partially explained by age-related differences in functional
      brain activity and formally tested these causal relationships. Functional MRI
      data was from groups of young and old adults engaged in an executive task
      switching experiment. Analyses were voxel-wise testing of moderated-mediation and
      simple mediation statistical path models to determine whether age group, brain
      activity and their interaction explained task performance in regions
      demonstrating an effect of age group. Results identified brain regions whose age
      related differences in functional brain activity significantly explained age
      related differences in task performance. In all identified locations, significant
      moderated-mediation relationships resulted from increasing brain activity
      predicting worse (slower) task performance in older but not younger adults.
      Findings suggest that advancing age links task performance to the level of brain
      activity. The overall message of this work is that in order to understand the
      role of functional brain activity on cognitive performance, analysis methods
      should respect theoretical relationships. Namely, that age affects brain activity
      and brain activity is related to task performance. 

PMID- 24672482
TI  - Benefits of physical exercise on basic visuo-motor functions across age.
AB  - Motor performance deficits of older adults are due to dysfunction at multiple
      levels. Age-related differences have been documented on executive functions;
      motor control becomes more reliant on cognitive control mechanisms, including the
      engagement of the prefrontal cortex (PFC), possibly compensating for age-related
      sensorimotor declines. Since at functional level the PFC showed the largest age
      related differences during discriminative response task, we wonder whether those
      effects are mainly due to the cognitive difficulty in stimulus discrimination or
      they could be also detected in a much easier task. In the present study, we
      measured the association of physical exercise with the PFC activation and
      response times (RTs) using a simple response task (SRT), in which the
      participants were asked to respond as quickly as possible by manual key-press to
      visual stimuli. Simultaneous behavioral (RTs) and electroencephalographic (EEG)
      recordings were performed on 84 healthy participants aged 19-86 years. The whole
      sample was divided into three cohorts (young, middle-aged, and older); each
      cohort was further divided into two equal sub-cohorts (exercise and not-exercise)
      based on a self-report questionnaire measuring physical exercise. The EEG signal
      was segmented in epochs starting 1100 prior to stimulus onset and lasting 2 s.
      Behavioral results showed age effects, indicating a slowing of RTs with
      increasing age. The EEG results showed a significant interaction between age and
      exercise on the activities recorded on the PFC. The results indicates that: (a)
      the brain of older adults needs the PFC engagement also to perform elementary
      task, such as the SRT, while this activity is not necessary in younger adults,
      (b) physical exercise could reduce this age-related reliance on extra cognitive
      control also during the performance of a SRT, and (c) the activity of the PFC is
      a sensitive index of the benefits of physical exercise on sensorimotor decline. 

PMID- 24672484
TI  - American ginseng acutely regulates contractile function of rat heart.
AB  - Chronic ginseng treatments have been purported to improve cardiac performance.
      However reports of acute administration of ginseng on cardiovascular function
      remain controversial and potential mechanisms are not clear. In this study, we
      examined the effects of acute North American ginseng (Panax quinquefolius)
      administration on rat cardiac contractile function by using electrocardiogram
      (ECG), non-invasive blood pressure (BP) measurement, and Langendorff isolated,
      spontaneously beating, perfused heart measurements (LP). Eight-week old male
      Sprague-Dawley rats (n = 8 per group) were gavaged with a single dose of water
      soluble American ginseng at 300 mg/kg body weight. Heart rate (HR) and BP were
      measured prior to and at 1 and 24 h after gavaging (ECG and BP). Additional
      groups were used for each time point for Langendorff measurements. HR was
      significantly decreased (ECG: 1 h: 6 +/- 0.2%, 24 h: 8 +/- 0.3%; BP: 1 h: 8.8 +/-
      0.2%, 24 h: 13 +/- 0.4% and LP: 1 h: 22 +/- 0.4%, 24 h: 19 +/- 0.4%) in rats
      treated with water-soluble ginseng compared with pre or control measures. An
      initial marked decrease in left ventricular developed pressure was observed in LP
      hearts but BP changes were not observed in BP group. A direct inhibitory effect
      of North American ginseng was observed on cardiac contractile function in LP rats
      and on fluorescence measurement of intracellular calcium transient in freshly
      isolated cardiac myocytes when exposed to ginseng (1 and 10 MUg/ml). Collectively
      these data present evidence of depressed cardiac contractile function by acute
      administration of North American ginseng in rat. This acute reduction in cardiac
      contractile function appears to be intrinsic to the myocardium. 

PMID- 24672483
TI  - Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with
      Decreased Network Efficiency within the Cerebro-Cerebellar System.
AB  - BACKGROUND: Deposition of cortical amyloid beta (Abeta) is a correlate of aging
      and a risk factor for Alzheimer disease (AD). While several higher order
      cognitive processes involve functional interactions between cortex and
      cerebellum, this study aims to investigate effects of cortical Abeta deposition
      on coupling within the cerebro-cerebellar system. METHODS: We included 15 healthy
      elderly subjects with normal cognitive performance as assessed by
      neuropsychological testing. Cortical Abeta was quantified using (11)carbon
      labeled Pittsburgh compound B positron-emission-tomography late frame signals.
      Volumes of brain structures were assessed by applying an automated parcelation
      algorithm to three dimensional magnetization-prepared rapid gradient-echo T1
      weighted images. Basal functional network activity within the cerebro-cerebellar
      system was assessed using blood-oxygen-level dependent resting state functional
      magnetic resonance imaging at the high field strength of 7 T for measuring
      coupling between cerebellar seeds and cerebral gray matter. A bivariate
      regression approach was applied for identification of brain regions with
      significant effects of individual cortical Abeta load on coupling. RESULTS:
      Consistent with earlier reports, a significant degree of positive and negative
      coupling could be observed between cerebellar seeds and cerebral voxels.
      Significant positive effects of cortical Abeta load on cerebro-cerebellar
      coupling resulted for cerebral brain regions located in inferior temporal lobe,
      prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. CONCLUSION:
      Our findings indicate that brain amyloidosis in cognitively normal elderly
      subjects is associated with decreased network efficiency within the cerebro
      cerebellar system. While the identified cerebral regions are consistent with
      established patterns of increased sensitivity for Abeta-associated
      neurodegeneration, additional studies are needed to elucidate the relationship
      between dysfunction of the cerebro-cerebellar system and risk for AD.

PMID- 24672485
TI  - CaMKII in sinoatrial node physiology and dysfunction.
AB  - The calcium and calmodulin-dependent protein kinase II (CaMKII) is present in
      sinoatrial node (SAN) pacemaker cells and is required for physiological "fight or
      flight" SAN beating rate responses. Inhibition of CaMKII in SAN does not affect
      baseline heart rate, but reduces heart rate increases in response to
      physiological stress. CaMKII senses intracellular calcium (Ca(2) (+)) changes,
      oxidation status, and hyperglycemia to phosphorylate substrates that regulate
      Ca(2) (+)-sensitive proteins, such as L-type Ca(2) (+) channels, phospholamban,
      and cardiac ryanodine receptors (RyR2). All of these substrates are involved in
      the SAN pacemaking mechanism. Excessive CaMKII activity, as occurs under
      pathological conditions such as heart failure, ischemia, and diabetes, can
      promote intracellular Ca(2) (+) overload and reactive oxygen species production.
      Oxidation of CaMKII (ox-CaMKII) locks CaMKII into a constitutively active
      configuration that contributes to SAN cell apoptosis and fibrosis. This ox-CaMKII
      mediated loss of functional SAN cells contributes to SAN dysfunction (SND) and
      sudden death. Thus, CaMKII has emerged as a central regulator of physiological
      SAN responses and a key determinant of SND. 

PMID- 24672486
TI  - Systematic review of near-infrared spectroscopy determined cerebral oxygenation
      during non-cardiac surgery.
AB  - Near-infrared spectroscopy (NIRS) is used to monitor regional cerebral
      oxygenation (rScO2) during cardiac surgery but is less established during non
      cardiac surgery. This systematic review aimed (i) to determine the non-cardiac
      surgical procedures that provoke a reduction in rScO2 and (ii) to evaluate
      whether an intraoperative reduction in rScO2 influences postoperative outcome.
      The PubMed and Embase database were searched from inception until April 30, 2013
      and inclusion criteria were intraoperative NIRS determined rScO2 in adult
      patients undergoing non-cardiac surgery. The type of surgery and number of
      patients included were recorded. There was included 113 articles and evidence
      suggests that rScO2 is reduced during thoracic surgery involving single lung
      ventilation, major abdominal surgery, hip surgery, and laparoscopic surgery with
      the patient placed in anti-Tredelenburg's position. Shoulder arthroscopy in the
      beach chair and carotid endarterectomy with clamped internal carotid artery (ICA)
      also cause pronounced cerebral desaturation. A >20% reduction in rScO2 coincides
      with indices of regional and global cerebral ischemia during carotid
      endarterectomy. Following thoracic surgery, major orthopedic, and abdominal
      surgery the occurrence of postoperative cognitive dysfunction (POCD) might be
      related to intraoperative cerebral desaturation. In conclusion, certain non
      cardiac surgical procedures is associated with an increased risk for the
      occurrence of rScO2. Evidence for an association between cerebral desaturation
      and postoperative outcome parameters other than cognitive dysfunction needs to be
      established. 

PMID- 24672487
TI  - Role of Pannexin-1 hemichannels and purinergic receptors in the pathogenesis of
      human diseases.
AB  - In the last decade several groups have determined the key role of hemichannels
      formed by pannexins or connexins, extracellular ATP and purinergic receptors in
      physiological and pathological conditions. Our work and the work of others,
      indicate that the opening of Pannexin-1 hemichannels and activation of purinergic
      receptors by extracellular ATP is essential for HIV infection, cellular
      migration, inflammation, atherosclerosis, stroke, and apoptosis. Thus, this
      review discusses the importance of purinergic receptors, Panx-1 hemichannels and
      extracellular ATP in the pathogenesis of several human diseases and their
      potential use to design novel therapeutic approaches. 

PMID- 24672489
TI  - Cx43 expression and function in the nervous system-implications for stem cell
      mediated regeneration.
AB  - Pathological conditions of the brain such as ischemia cause major sensorimotor
      and cognitive impairments. In novel therapeutic approaches to brain injury, stem
      cells have been applied to ameliorate the pathological outcome. In several
      experimental models, including hypoxia-ischemia and trauma, transplantation of
      stem cells correlated with an improved functional and structural outcome. At the
      cellular level, brain insults also change gap junction physiology and expression,
      leading to altered intercellular communication. Differences in expression in
      response to brain injury have been detected in particular in Cx43, the major
      astrocytic gap junction protein, and its overexpression or deletion was
      associated with the pathophysiological outcome. We here focus on Cx43 changes in
      host tissue mediated by stem cells. Stem cell-induced changes in connexin
      expression, and consecutively in gap junction channel or hemichannel function,
      might play a part in altered cell interaction, intercellular communication, and
      neural cell survival, and thereby contribute to the beneficial effects of
      transplanted stem cells. 

PMID- 24672490
TI  - Aggression traits in youth psychopathy: the key role of serotonin.

PMID- 24672488
TI  - Skeletal muscle wasting with disuse atrophy is multi-dimensional: the response
      and interaction of myonuclei, satellite cells and signaling pathways.
AB  - Maintenance of skeletal muscle is essential for health and survival. There are
      marked losses of skeletal muscle mass as well as strength and physiological
      function under conditions of low mechanical load, such as space flight, as well
      as ground based models such as bed rest, immobilization, disuse, and various
      animal models. Disuse atrophy is caused by mechanical unloading of muscle and
      this leads to reduced muscle mass without fiber attrition. Skeletal muscle stem
      cells (satellite cells) and myonuclei are integrally involved in skeletal muscle
      responses to environmental changes that induce atrophy. Myonuclear domain size is
      influenced differently in fast and slow twitch muscle, but also by different
      models of muscle wasting, a factor that is not yet understood. Although the
      myonuclear domain is 3-dimensional this is rarely considered. Apoptosis as a
      mechanism for myonuclear loss with atrophy is controversial, whereas cell death
      of satellite cells has not been considered. Molecular signals such as
      myostatin/SMAD pathway, MAFbx, and MuRF1 E3 ligases of the ubiquitin proteasome
      pathway and IGF1-AKT-mTOR pathway are 3 distinctly different contributors to
      skeletal muscle protein adaptation to disuse. Molecular signaling pathways
      activated in muscle fibers by disuse are rarely considered within satellite cells
      themselves despite similar exposure to unloading or low mechanical load. These
      molecular pathways interact with each other during atrophy and also when various
      interventions are applied that could alleviate atrophy. Re-applying mechanical
      load is an obvious method to restore muscle mass, however how nutrient
      supplementation (e.g., amino acids) may further enhance recovery (or reduce
      atrophy despite unloading or ageing) is currently of great interest. Satellite
      cells are particularly responsive to myostatin and to growth factors. Recently,
      the hibernating squirrel has been identified as an innovative model to study
      resistance to atrophy. 

PMID- 24672491
TI  - The trauma of peer abuse: effects of relational peer victimization and social
      anxiety disorder on physiological and affective reactions to social exclusion.
AB  - BACKGROUND: Social exclusion elicits emotional distress, negative mood, and
      physiological stress. Recent studies showed that these effects were more intense
      and persisting in socially anxious subjects. The present study examined whether
      the abnormal reactions of socially anxious subjects can be traced back to
      previous experiences of relational peer victimization during childhood and
      adolescence. METHODS: Participants (N = 74) were patients with a diagnosis of
      social anxiety disorder as well as healthy controls. The patient and control
      groups were subdivided into two subgroups according to the subject's reports
      about previous relational peer victimization. Immediate and delayed physiological
      (skin conductance level and heart rate) and affective reactions to a simulated
      social exclusion in a ball-toss game (Cyberball) were recorded. RESULTS: Overall,
      subjects' immediate reactions to social exclusion were an increase in skin
      conductance and a reduction of positive affect. Regardless of the diagnostic
      status, subjects with a history of relational peer victimization showed a more
      intense self-reported affective change that was accompanied by a blunted skin
      conductance response. However, the mood of the subjects with a history of peer
      victimization recovered during a 15 min waiting period. A diagnosis of social
      anxiety disorder did not affect the reactions to social exclusion on any measure.
      CONCLUSION: Findings indicate that stress reactions to social exclusion depend
      more on previous experiences of peer victimization than on a diagnosis of social
      anxiety disorder. The findings indicate that memories of negative social
      experiences can determine the initial stress reaction to social threats.

PMID- 24672493
TI  - Humans (really) are animals: picture-book reading influences 5-year-old urban
      children's construal of the relation between humans and non-human animals.
AB  - What is the relation between humans and non-human animals? From a biological
      perspective, we view humans as one species among many, but in the fables and
      films we create for children, we often offer an anthropocentric perspective,
      imbuing non-human animals with human-like characteristics. What are the
      consequences of these distinctly different perspectives on children's reasoning
      about the natural world? Some have argued that children universally begin with an
      anthropocentric perspective and that acquiring a biological perspective requires
      a basic conceptual change (cf. Carey, 1985). But recent work reveals that this
      anthropocentric perspective, evidenced in urban 5-year-olds, is not evident in 3
      year-olds (Herrmann etal., 2010). This indicates that the anthropocentric
      perspective is not an obligatory first step in children's reasoning about
      biological phenomena. In the current paper, we introduced a priming manipulation
      to assess whether 5-year-olds' reasoning about a novel biological property is
      influenced by the perspectives they encounter in children's books. Just before
      participating in a reasoning task, each child read a book about bears with an
      experimenter. What varied was whether bears were depicted from an anthropomorphic
      (Berenstain Bears) or biological perspective (Animal Encyclopedia). The priming
      had a dramatic effect. Children reading the Berenstain Bears showed the standard
      anthropocentric reasoning pattern, but those reading the Animal Encyclopedia
      adopted a biological pattern. This offers evidence that urban 5-year-olds can
      adopt either a biological or a human-centered stance, depending upon the context.
      Thus, children's books and other media are double-edged swords. Media may
      (inadvertently) support human-centered reasoning in young children, but may also
      be instrumental in redirecting children's attention to a biological model. 

PMID- 24672492
TI  - Dynamic musical communication of core affect.
AB  - Is there something special about the way music communicates feelings? Theorists
      since Meyer (1956) have attempted to explain how music could stimulate varied and
      subtle affective experiences by violating learned expectancies, or by mimicking
      other forms of social interaction. Our proposal is that music speaks to the brain
      in its own language; it need not imitate any other form of communication. We
      review recent theoretical and empirical literature, which suggests that all
      conscious processes consist of dynamic neural events, produced by spatially
      dispersed processes in the physical brain. Intentional thought and affective
      experience arise as dynamical aspects of neural events taking place in multiple
      brain areas simultaneously. At any given moment, this content comprises a unified
      "scene" that is integrated into a dynamic core through synchrony of neuronal
      oscillations. We propose that (1) neurodynamic synchrony with musical stimuli
      gives rise to musical qualia including tonal and temporal expectancies, and that
      (2) music-synchronous responses couple into core neurodynamics, enabling music to
      directly modulate core affect. Expressive music performance, for example, may
      recruit rhythm-synchronous neural responses to support affective communication.
      We suggest that the dynamic relationship between musical expression and the
      experience of affect presents a unique opportunity for the study of emotional
      experience. This may help elucidate the neural mechanisms underlying arousal and
      valence, and offer a new approach to exploring the complex dynamics of the how
      and why of emotional experience. 

PMID- 24672494
TI  - The processing of coherent global form and motion patterns without visual
      awareness.
AB  - In the present study we addressed whether the processing of global form and
      motion was dependent on visual awareness. Continuous flash suppression (CFS) was
      used to suppress from awareness global dot motion (GDM) and Glass pattern
      stimuli. We quantified the minimum time taken for both pattern types to break
      suppression with the signal coherence of the pattern (0, 25, 50, and 100% signal)
      and the type of global structure (rotational, and radial) as independent
      variables. For both form and motion patterns increasing signal coherence
      decreased the time required to break suppression. This was the same for both
      rotational and radial global patterns. However, GDM patterns broke suppression
      faster than Glass patterns. In a supplementary experiment, we confirmed that this
      difference in break times is not because of the temporal nature of GDM patterns
      in attracting attention. In Experiment 2, we examined whether the processing of
      dynamic Glass patterns were similarly dependent on visual awareness. The
      processing of dynamic Glass patterns is involves both motion and form systems,
      and we questioned whether the interaction of these two systems was dependent on
      visual awareness. The suppression of dynamic Glass patterns was also dependent on
      signal coherence and the time course of suppression break resembled the detection
      of global motion and not global form. In Experiment 3 we ruled out the
      possibility that faster suppression break times was because the visual system is
      more sensitive to highly coherent form and motion patterns. Here contrast
      changing GDM and Glass patterns were superimposed on the dynamic CFS mask, and
      the minimum time required for them to be detected was measured. We showed that
      there was no difference in detection times for patterns of 0 and 100% coherence.
      The advantage of highly coherent global motion and form patterns in breaking
      suppression indicated that the processing and interaction of global motion and
      form systems occur without visual awareness. 

PMID- 24672495
TI  - The other-race effect in 3-year-old German and Cameroonian children.
AB  - Recognizing individual faces is an important human ability that highly depends on
      experience. This is reflected in the so called other-race effect; adults are
      better at recognizing faces from their own ethnic group, while very young infants
      do not show this specialization yet. Two experiments examined whether 3-year-old
      children from two different cultural backgrounds show the other-race effect. In
      Experiment 1, German children (N = 41) were presented with a forced choice
      paradigm where they were asked to recognize female Caucasian or African faces. In
      Experiment 2, 3-year-olds from Cameroon (N = 66) participated in a similar task
      using the same stimulus material. In both cultures the other-race effect was
      present; children were better at recognizing individual faces from their own
      ethnic group. In addition, German children performed at a higher overall level of
      accuracy than Cameroonians. The results are discussed in relation to cultural
      aspects in particular. 

PMID- 24672496
TI  - Fronto-parietal and fronto-temporal theta phase synchronization for visual and
      auditory-verbal working memory.
AB  - In humans, theta phase (4-8 Hz) synchronization observed on
      electroencephalography (EEG) plays an important role in the manipulation of
      mental representations during working memory (WM) tasks; fronto-temporal
      synchronization is involved in auditory-verbal WM tasks and fronto-parietal
      synchronization is involved in visual WM tasks. However, whether or not theta
      phase synchronization is able to select the to-be-manipulated modalities is
      uncertain. To address the issue, we recorded EEG data from subjects who were
      performing auditory-verbal and visual WM tasks; we compared the theta
      synchronizations when subjects performed either auditory-verbal or visual
      manipulations in separate WM tasks, or performed both two manipulations in the
      same WM task. The auditory-verbal WM task required subjects to calculate numbers
      presented by an auditory-verbal stimulus, whereas the visual WM task required
      subjects to move a spatial location in a mental representation in response to a
      visual stimulus. The dual WM task required subjects to manipulate auditory
      verbal, visual, or both auditory-verbal and visual representations while
      maintaining auditory-verbal and visual representations. Our time-frequency EEG
      analyses revealed significant fronto-temporal theta phase synchronization during
      auditory-verbal manipulation in both auditory-verbal and auditory-verbal/visual
      WM tasks, but not during visual manipulation tasks. Similarly, we observed
      significant fronto-parietal theta phase synchronization during visual
      manipulation tasks, but not during auditory-verbal manipulation tasks. Moreover,
      we observed significant synchronization in both the fronto-temporal and fronto
      parietal theta signals during simultaneous auditory-verbal/visual manipulations.
      These findings suggest that theta synchronization seems to flexibly connect the
      brain areas that manipulate WM. 

PMID- 24672497
TI  - Clinical knowledge, health policies and social identities. Commentary on Lara
      Rzesnitzek (2013) "Early psychosis as a mirror of biologist controversies in post
      war German, Anglo-Saxon and Soviet psychiatry".

PMID- 24672498
TI  - A rodent version of the Iowa Gambling Task: 7 years of progress.
AB  - In the Iowa Gambling Task (IGT) subjects need to find a way to earn money in a
      context of variable wins and losses, conflicting short-term and long-term pay
      off, and uncertainty of outcomes. In 2006, we published the first rodent version
      of the IGT (r-IGT; Behavior Research Methods 38, 470-478). Here, we discuss
      emerging ideas on the involvement of different prefrontal-striatal networks in
      task-progression in the r-IGT, as revealed by our studies thus far. The emotional
      system, encompassing, among others, the orbitofrontal cortex, infralimbic cortex
      and nucleus accumbens (shell and core area), may be involved in assessing and
      anticipating the value of different options in the early stages of the task,
      i.e., as animals explore and learn task contingencies. The cognitive control
      system, encompassing, among others, the prelimbic cortex and dorsomedial
      striatum, may be involved in instrumental goal-directed behavior in later stages
      of the task, i.e., as behavior toward long-term options is strengthened
      (reinforced) and behavior toward long-term poor options is weakened (punished).
      In addition, we suggest two directions for future research: (1) the role of the
      internal state of the subject in decision-making, and (2) studying differences in
      task-related costs. Overall, our studies have contributed to understanding the
      interaction between the emotional system and cognitive control system as crucial
      to navigating human and non-human animals alike through a world of variable wins
      and losses, conflicting short-term and long-term pay-offs, and uncertainty of
      outcomes. 

PMID- 24672499
TI  - A little more conversation - the influence of communicative context on syntactic
      priming in brain and behavior.
AB  - We report on an functional magnetic resonance imaging (fMRI) syntactic priming
      experiment in which we measure brain activity for participants who communicate
      with another participant outside the scanner. We investigated whether syntactic
      processing during overt language production and comprehension is influenced by
      having a (shared) goal to communicate. Although theory suggests this is true, the
      nature of this influence remains unclear. Two hypotheses are tested: (i)
      syntactic priming effects (fMRI and behavioral) are stronger for participants in
      the communicative context than for participants doing the same experiment in a
      non-communicative context, and (ii) syntactic priming magnitude (behavioral) is
      correlated with the syntactic priming magnitude of the speaker's communicative
      partner. Results showed that across conditions, participants were faster to
      produce sentences with repeated syntax, relative to novel syntax. This behavioral
      result converged with the fMRI data: we found repetition suppression effects in
      the left insula extending into left inferior frontal gyrus (BA 47/45), left
      middle temporal gyrus (BA 21), left inferior parietal cortex (BA 40), left
      precentral gyrus (BA 6), bilateral precuneus (BA 7), bilateral supplementary
      motor cortex (BA 32/8), and right insula (BA 47). We did not find support for the
      first hypothesis: having a communicative intention does not increase the
      magnitude of syntactic priming effects (either in the brain or in behavior) per
      se. We did find support for the second hypothesis: if speaker A is
      strongly/weakly primed by speaker B, then speaker B is primed by speaker A to a
      similar extent. We conclude that syntactic processing is influenced by being in a
      communicative context, and that the nature of this influence is bi-directional:
      speakers are influenced by each other. 

PMID- 24672500
TI  - Eye movements when viewing advertisements.
AB  - In this selective review, we examine key findings on eye movements when viewing
      advertisements. We begin with a brief, general introduction to the properties and
      neural underpinnings of saccadic eye movements. Next, we provide an overview of
      eye movement behavior during reading, scene perception, and visual search, since
      each of these activities is, at various times, involved in viewing ads. We then
      review the literature on eye movements when viewing print ads and warning labels
      (of the kind that appear on alcohol and tobacco ads), before turning to a
      consideration of advertisements in dynamic media (television and the Internet).
      Finally, we propose topics and methodological approaches that may prove to be
      useful in future research. 

PMID- 24672501
TI  - Online advertisement: how are visual strategies affected by the distance and the
      animation of banners?
AB  - Most of studies about online advertisements have indicated that they have a
      negative impact on users' cognitive processes, especially when they include
      colorful or animated banners and when they are close to the text to be read. In
      the present study we assessed the effects of two advertisements features-distance
      from the text and the animation-on visual strategies during a word-search task
      and a reading-for-comprehension task using Web-like pages. We hypothesized that
      the closer the advertisement was to the target text, the more cognitive
      processing difficulties it would cause. We also hypothesized that (1) animated
      banners would be more disruptive than static advertisements and (2) banners would
      have more effect on word-search performance than reading-for-comprehension
      performance. We used an automatic classifier to assess variations in use of
      Scanning and Reading visual strategies during task performance. The results
      showed that the effect of dynamic and static advertisements on visual strategies
      varies according to the task. Fixation duration indicated that the closest
      advertisements slowed down information processing but there was no difference
      between the intermediate (40 pixel) and far (80 pixel) distance conditions. Our
      findings suggest that advertisements have a negative impact on users' performance
      mostly when a lots of cognitive resources are required as for reading-for
      comprehension. 

PMID- 24672502
TI  - An effect of inhibitory load in children while keeping working memory load
      constant.
AB  - Children are slower and more error-prone when the correct response is counter to
      their initial inclination (incongruent trials) than when they just need to do
      what comes naturally (congruent trials). Children are almost always tested on a
      congruent-trial block and then on an incongruent-trial block. That order of
      testing makes it impossible to determine whether worse performance on incongruent
      trials is due to the need to inhibit a pre-potent response, the need to clear the
      rule for Block 1 from working memory, some other demand of task-switching, or
      some combination of these. However, if the congruent block and incongruent blocks
      each have only one rule (e.g., "press on the same side as the stimulus" for
      congruent trials and "press on the side opposite the stimulus" for incongruent
      trials, as on the hearts and flowers task) and children's performance when the
      incongruent block is presented first is fully comparable to their performance
      when it is presented second, the only possible explanation for their worse
      performance on incongruent versus congruent trials would seem to be the added
      inhibitory demand on incongruent trials. Certainly, worse performance on Block 1
      would not be due to inefficient clearing of working memory or task-switching
      demands. We tested 96 children (49 girls) 6-10 years of age on the hearts and
      flowers test with order of congruent and incongruent blocks counterbalanced
      across children. Children were slower and made more errors on incongruent trials
      regardless of task order. We expected task-switching demands to account for some
      of the variance, but to our surprise, performance was fully comparable on the
      incongruent block whether it came first or second. These results indicate that
      increasing inhibitory demands alone is sufficient to impair children's
      performance in the face of no change in working memory demands, suggesting that
      inhibition is a separate mental function from working memory. 

PMID- 24672503
TI  - Exploring the factor structure of the Food Cravings Questionnaire-Trait in Cuban
      adults.
AB  - Food cravings refer to an intense desire to eat specific foods. The Food Cravings
      Questionnaire-Trait (FCQ-T) is the most commonly used instrument to assess food
      cravings as a multidimensional construct. Its 39 items have an underlying nine
      factor structure for both the original English and Spanish version; but
      subsequent studies yielded fewer factors. As a result, a 15-item version of the
      FCQ-T with one-factor structure has been proposed (FCQ-T-reduced; see this
      Research Topic). The current study aimed to explore the factor structure of the
      Spanish version for both the FCQ-T and FCQ-T-reduced in a sample of 1241 Cuban
      adults. Results showed a four-factor structure for the FCQ-T, which explained 55%
      of the variance. Factors were highly correlated. Using the items of the FCQ-T
      reduced only showed a one-factor structure, which explained 52% of the variance.
      Both versions of the FCQ-T were positively correlated with body mass index (BMI),
      scores on the Food Thoughts Suppression Inventory and weight cycling. In
      addition, women had higher scores than men and restrained eaters had higher
      scores than unrestrained eaters. To summarize, results showed that (1) the FCQ-T
      factor structure was significantly reduced in Cuban adults and (2) the FCQ-T
      reduced may represent a good alternative to efficiently assess food craving on a
      trait level. 

PMID- 24672504
TI  - The neuroscientific study of spiritual practices.
AB  - The purpose of this paper will be to provide a perspective on the current state
      of the research evaluating the neurobiological correlates of spiritual practices
      and review the methodological issues that confront this research field. There are
      many types of spiritual practices that might be studied including prayer and
      meditation, as well as unusual practices such as mediumistic trance states,
      speaking in tongues, and also drug-induced experiences. Current studies have
      utilized neuroimaging techniques including functional magnetic resonance imaging,
      single photon emission computed tomography, and positron emission tomography.
      These studies have helped elucidate the neurobiological mechanisms associated
      with spiritual practices. Such studies confront unique challenges for scientific
      methodology including determining the most appropriate objective measures such as
      neuroimaging studies and physiological parameters, and correlating them with
      subjective measures that help capture states of spiritual significance. Overall,
      a neuroscientific study of spiritual practices and experiences has the potential
      to provide fascinating data to further our understanding of the relationship
      between the brain and such phenomena. 

PMID- 24672505
TI  - Compound words prompt arbitrary semantic associations in conceptual memory.
AB  - Linguistic relativity theory has received empirical support in domains such as
      color perception and object categorization. It is unknown, however, whether
      relations between words idiosyncratic to language impact non-verbal
      representations and conceptualizations. For instance, would one consider the
      concepts of horse and sea as related were it not for the existence of the
      compound seahorse? Here, we investigated such arbitrary conceptual relationships
      using a non-linguistic picture relatedness task in participants undergoing event
      related brain potential recordings. Picture pairs arbitrarily related because of
      a compound and presented in the compound order elicited N400 amplitudes similar
      to unrelated pairs. Surprisingly, however, pictures presented in the reverse
      order (as in the sequence horse-sea) reduced N400 amplitudes significantly,
      demonstrating the existence of a link in memory between these two concepts
      otherwise unrelated. These results break new ground in the domain of linguistic
      relativity by revealing predicted semantic associations driven by lexical
      relations intrinsic to language. 

PMID- 24672506
TI  - Consciousness: a neural capacity for objectivity, especially pronounced in
      humans.
AB  - Consciousness tends to be viewed either as subjective experience of sensations
      and feelings, or as perception and internal representation of objects. This paper
      argues that neither view sufficiently acknowledges that consciousness may refer
      to the brain's most adaptive property: its capacity to produce states of
      objectivity. It is proposed that this capacity relies on multiple sensorimotor
      networks for internally representing objects and their properties in terms of
      expectancies, as well as on motivational and motor mechanisms involved in
      exploration, play, and care for vulnerable living and non-living objects. States
      of objectivity are associated with a very special phenomenal aspect; the
      experience that subjective aspects are absent and one is "just looking" at the
      world as it really is and can be. However, these states are normally closely
      preceded and followed by (and tend to be combined or fused with) sensations and
      feelings which are caused by activation of sensory and motivational mechanisms. A
      capacity for objectivity may have evolved in different species and can be
      conceived as a common basis for other elusive psychological properties such as
      intelligence, conscience, and esthetic experience; all three linked to crucial
      behaviors in human evolution such as tool making, cooperation, and art. The
      brain's pervasive tendency to objectify may be responsible for wrongly equating
      consciousness with feelings and wrongly opposing it to well-learned or habitual
      ("unconscious") patterns of perception and behavior. 

PMID- 24672507
TI  - Visual target distance, but not visual cursor path length produces shifts in
      motor behavior.
AB  - When using tools effects in body space and distant space often do not correspond.
      Findings so far demonstrated that in this case visual feedback has more impact on
      action control than proprioceptive feedback. The present study varies the
      dimensional overlap between visual and proprioceptive action effects and
      investigates its impact on aftereffects in motor responses. In two experiments
      participants perform linear hand movements on a covered digitizer tablet to
      produce ?-shaped cursor trajectories on the display. The shape of hand motion and
      cursor motion (linear vs. curved) is dissimilar and therefore does not overlap.
      In one condition the length of hand amplitude and visual target distance is
      similar and constant while the length of the cursor path is dissimilar and
      varies. In another condition the length of the hand amplitude varies while the
      lengths of visual target distance (similar or dissimilar) and cursor path
      (dissimilar) are constant. First, we found that aftereffects depended on the
      relation between hand path length and visual target distance, and not on the
      relation between hand and cursor path length. Second, increasing contextual
      interference did not reveal larger aftereffects. Finally, data exploration
      demonstrated a considerable benefit from gain repetitions across trials when
      compared to gain switches. In conclusion, dimensional overlap between visual and
      proprioceptive action effects modulates human information processing in visually
      controlled actions. However, adjustment of the internal model seems to occur very
      fast for this kind of simple linear transformation, so that the impact of prior
      visual feedback is fleeting. 

PMID- 24672508
TI  - Age-related trends of inhibitory control in Stroop-like big-small task in 3 to 12
      year-old children and young adults.
AB  - Inhibitory control is the ability to suppress competing, dominant, automatic, or
      prepotent cognitive processing at perceptual, intermediate, and output stages.
      Inhibitory control is a key cognitive function of typical and atypical child
      development. This study examined age-related trends of Stroop-like interference
      in 3 to 12-year-old children and young adults by administration of a computerized
      Stroop-like big-small task with reduced working memory demand. This task used a
      set of pictures displaying a big and small circle in black and included the same
      condition and the opposite condition. In the same condition, each participant was
      instructed to say "big" when viewing the big circle and to say "small" when
      viewing the small circle. In the opposite condition, each participant was
      instructed to say "small" when viewing the big circle and to say "big" when
      viewing the small circle. The opposite condition required participants to inhibit
      the prepotent response of saying the same, a familiar response to a perceptual
      stimulus. The results of this study showed that Stroop-like interference
      decreased markedly in children in terms of error rates and correct response time.
      There was no deterioration of performance occurring between the early trials and
      the late trials in the sessions of the day-night task. Moreover, pretest failure
      rate was relatively low in this study. The Stroop-like big-small task is a useful
      tool to assess the development of inhibitory control in young children in that
      the task is easy to understand and has small working memory demand. 

PMID- 24672509
TI  - Estimating true standard deviations.

PMID- 24672510
TI  - Structural qualia: a solution to the hard problem of consciousness.
AB  - The hard problem of consciousness has been often claimed to be unsolvable by the
      methods of traditional empirical sciences. It has been argued that all the
      objects of empirical sciences can be fully analyzed in structural terms but that
      consciousness is (or has) something over and above its structure. However, modern
      neuroscience has introduced a theoretical framework in which also the apparently
      non-structural aspects of consciousness, namely the so called qualia or
      qualitative properties, can be analyzed in structural terms. That framework
      allows us to see qualia as something compositional with internal structures that
      fully determine their qualitative nature. Moreover, those internal structures can
      be identified which certain neural patterns. Thus consciousness as a whole can be
      seen as a complex neural pattern that misperceives some of its own highly complex
      structural properties as monadic and qualitative. Such neural pattern is
      analyzable in fully structural terms and thereby the hard problem is solved. 

PMID- 24672511
TI  - Vibrio chromosome-specific families.
AB  - We have compared chromosome-specific genes in a set of 18 finished Vibrio
      genomes, and, in addition, also calculated the pan- and core-genomes from a data
      set of more than 250 draft Vibrio genome sequences. These genomes come from 9
      known species and 2 unknown species. Within the finished chromosomes, we find a
      core set of 1269 encoded protein families for chromosome 1, and a core of 252
      encoded protein families for chromosome 2. Many of these core proteins are also
      found in the draft genomes (although which chromosome they are located on is
      unknown.) Of the chromosome specific core protein families, 1169 and 153 are
      uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO) terms for
      each of the protein families were determined, and the different sets for each
      chromosome were compared. A total of 363 different "Molecular Function" GO
      categories were found for chromosome 1 specific protein families, and these
      include several broad activities: pyridoxine 5' phosphate synthetase,
      glucosylceramidase, heme transport, DNA ligase, amino acid binding, and ribosomal
      components; in contrast, chromosome 2 specific protein families have only 66
      Molecular Function GO terms and include many membrane-associated activities, such
      as ion channels, transmembrane transporters, and electron transport chain
      proteins. Thus, it appears that whilst there are many "housekeeping systems"
      encoded in chromosome 1, there are far fewer core functions found in chromosome
      2. However, the presence of many membrane-associated encoded proteins in
      chromosome 2 is surprising. 

PMID- 24672512
TI  - Reduced disease in black abalone following mass mortality: phage therapy and
      natural selection.
AB  - Black abalone, Haliotis cracherodii, populations along the NE Pacific ocean have
      declined due to the rickettsial disease withering syndrome (WS). Natural recovery
      on San Nicolas Island (SNI) of Southern California suggested the development of
      resistance in island populations. Experimental challenges in one treatment
      demonstrated that progeny of disease-selected black abalone from SNI survived
      better than did those from naive black abalone from Carmel Point in mainland
      coastal central California. Unexpectedly, the presence of a newly observed
      bacteriophage infecting the WS rickettsia (WS-RLO) had strong effects on the
      survival of infected abalone. Specifically, presence of phage-infected RLO (RLOv)
      reduced the host response to infection, RLO infection loads, and associated
      mortality. These data suggest that the black abalone: WS-RLO relationship is
      evolving through dual host mechanisms of resistance to RLO infection in the
      digestive gland via tolerance to infection in the primary target tissue (the post
      esophagus) coupled with reduced pathogenicity of the WS-RLO by phage infection,
      which effectively reduces the infection load in the primary target tissue by
      half. Sea surface temperature patterns off southern California, associated with a
      recent hiatus in global-scale ocean warming, do not appear to be a sufficient
      explanation for survival patterns in SNI black abalone. These data highlight the
      potential for natural recovery of abalone populations over time and that further
      understanding of mechanisms governing host-parasite relationships will better
      enable us to manage declining populations. 

PMID- 24672513
TI  - Insusceptibility to disinfectants in bacteria from animals, food and humans-is
      there a link to antimicrobial resistance?
AB  - Enterococcus faecalis (n = 834) and Enterococcus faecium (n = 135) from blood and
      feces of hospitalized humans, from feces of outpatients and livestock and from
      food were screened for their susceptibility to a quaternary ammonium compound
      (didecyldimethylammoniumchloride, DDAC) and to 28 antibiotics by micro
      /macrodilution. The maximum DDAC-MIC in our field study was 3.5 mg/l, but after
      adaptation in the laboratory, MIC values of 21.9 mg/l were observed. Strains for
      which DDAC had MICs > 1.4 mg/l ("non-wildtype," in total: 46 of 969
      isolates/4.7%) were most often found in milk and dairy products (14.6%), while
      their prevalence in livestock was generally low (0-4%). Of human isolates, 2.9
      6.8% had a "non-wildtype" phenotype. An association between reduced
      susceptibility to DDAC, high-level-aminoglycoside resistance and aminopenicillin
      resistance was seen in E. faecium (p < 0.05). No indications for a common source
      of non-wildtype strains were found by RAPD-PCR; however, several non-wildtype E.
      faecalis shared the same variant of the emeA-gene. In addition, bacteria (n = 42)
      of different genera were isolated from formic acid based boot bath disinfectant
      (20 ml of 55% formic acid/l). The MICs of this disinfectant exceeded the wildtype
      MICs up to 20-fold (staphylococci), but were still one to three orders of
      magnitude below the used concentration of the disinfectant (i. e., 1.1% formic
      acid). In conclusion, the bacterial susceptibility to disinfectants still seems
      to be high. Thus, the proper use of disinfectants in livestock surroundings along
      with a good hygiene praxis should still be highly encouraged. Hints to a link
      between antibiotic resistance and reduced susceptibility for disinfectants-as
      seen for E. faecium-should be substantiated in further studies and might be an
      additional reason to confine the use of antibiotics. 

PMID- 24672514
TI  - Death by a thousand cuts: the challenges and diverse landscape of lignocellulosic
      hydrolysate inhibitors.
AB  - Lignocellulosic hydrolysate (LCH) inhibitors are a large class of bioactive
      molecules that arise from pretreatment, hydrolysis, and fermentation of plant
      biomass. These diverse compounds reduce lignocellulosic biofuel yields by
      inhibiting cellular processes and diverting energy into cellular responses. LCH
      inhibitors present one of the most significant challenges to efficient biofuel
      production by microbes. Development of new strains that lessen the effects of LCH
      inhibitors is an economically favorable strategy relative to expensive
      detoxification methods that also can reduce sugar content in deconstructed
      biomass. Systems biology analyses and metabolic modeling combined with directed
      evolution and synthetic biology are successful strategies for biocatalyst
      development, and methods that leverage state-of-the-art tools are needed to
      overcome inhibitors more completely. This perspective considers the energetic
      costs of LCH inhibitors and technologies that can be used to overcome their drain
      on conversion efficiency. We suggest academic and commercial research groups
      could benefit by sharing data on LCH inhibitors and implementing "translational
      biofuel research." 

PMID- 24672515
TI  - Identification of key components in the energy metabolism of the
      hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus by
      transcriptome analyses.
AB  - Energy conservation via the pathway of dissimilatory sulfate reduction is present
      in a diverse group of prokaryotes, but is most comprehensively studied in
      Deltaproteobacteria. In this study, whole-genome microarray analyses were used to
      provide a model of the energy metabolism of the sulfate-reducing archaeon
      Archaeoglobus fulgidus, based on comparative analysis of litoautotrophic growth
      with H2/CO2 and thiosulfate, and heterotrophic growth on lactate with sulfate or
      thiosulfate. Only 72 genes were expressed differentially between the cultures
      utilizing sulfate or thiosulfate, whereas 269 genes were affected by a shift in
      energy source. We identified co-located gene cluster encoding putative lactate
      dehydrogenases (LDHs; lldD, dld, lldEFG), also present in sulfate-reducing
      bacteria. These enzymes may take part in energy conservation in A. fulgidus by
      specifically linking lactate oxidation with APS reduction via the Qmo complex.
      High transcriptional levels of Fqo confirm an important role of F420H2, as well
      as a menaquinone-mediated electron transport chain, during heterotrophic growth.
      A putative periplasmic thiosulfate reductase was identified by specific up
      regulation. Also, putative genes for transport of sulfate and sulfite are
      discussed. We present a model for hydrogen metabolism, based on the probable
      bifurcation reaction of the Mvh:Hdl hydrogenase, which may inhibit the
      utilization of Fdred for energy conservation. Energy conservation is probably
      facilitated via menaquinone to multiple membrane-bound heterodisulfide reductase
      (Hdr) complexes and the DsrC protein-linking periplasmic hydrogenase (Vht) to the
      cytoplasmic reduction of sulfite. The ambiguous roles of genes corresponding to
      fatty acid metabolism induced during growth with H2 are discussed. Putative co
      assimilation of organic acids is favored over a homologous secondary carbon
      fixation pathway, although both mechanisms may contribute to conserve the amount
      of Fdred needed during autotrophic growth with H2. 

PMID- 24672516
TI  - The impact of antifungals on toll-like receptors.
AB  - Fungi are increasingly recognized as major pathogens in immunocompromised
      individuals. With the increase in the number of fungal infections each year and
      the development of resistance to current therapy, new approaches to treatment
      including stimulation of the immune response in addition to concurrent
      pharmacotherapy is ongoing. The most common invasive fungal infections are caused
      by Candida spp., Aspergillus spp., and Cryptococcus spp. Amphotericin B (AmB) has
      remained the cornerstone of therapy against many fulminant fungal infections but
      its use is limited by its multitude of side effects. Echinocandins are a newer
      class of antifungal drugs with activity against Candida spp. and Aspergillus spp.
      and constitutes an alternative to AmB due to superior patient tolerability and
      fewer side effects. Due to their oral delivery, azoles continue to be heavily
      used for simple and complex diseases, such as fluconazole for candidal vaginitis
      and voriconazole for aspergillosis. The objective of this paper is to present
      current knowledge regarding the multiple interactions between the broad spectrum
      antifungals and the innate immune response, primarily focusing on the toll-like
      receptors. 

PMID- 24672517
TI  - Identification of carotenoids from the extremely halophilic archaeon Haloarcula
      japonica.
AB  - The carotenoids produced by extremely halophilic archaeon Haloarcula japonica
      were extracted and identified by their chemical, chromatographic, and
      spectroscopic characteristics (UV-Vis and mass spectrometry). The composition
      (mol%) was 68.1% bacterioruberin, 22.5% monoanhydrobacterioruberin, 9.3%
      bisanhydrobacterioruberin, <0.1% isopentenyldehydrorhodopin, and trace amounts of
      lycopene and phytoene. The in vitro scavenging capacity of a carotenoid,
      bacterioruberin, extracted from Haloarcula japonica cells against 1,1-diphenyl-2
      picrylhydrazyl (DPPH) radicals was evaluated. The antioxidant capacity of
      bacterioruberin was much higher than that of beta -carotene. 

PMID- 24672519
TI  - Microbial regulation of global biogeochemical cycles.

PMID- 24672520
TI  - Stormwater runoff drives viral community composition changes in inland
      freshwaters.
AB  - Storm events impact freshwater microbial communities by transporting terrestrial
      viruses and other microbes to freshwater systems, and by potentially resuspending
      microbes from bottom sediments. The magnitude of these impacts on freshwater
      ecosystems is unknown and largely unexplored. Field studies carried out at two
      discrete sites in coastal Virginia (USA) were used to characterize the viral load
      carried by runoff and to test the hypothesis that terrestrial viruses introduced
      through stormwater runoff change the composition of freshwater microbial
      communities. Field data gathered from an agricultural watershed indicated that
      primary runoff can contain viral densities approximating those of receiving
      waters. Furthermore, viruses attached to suspended colloids made up a large
      fraction of the total load, particularly in early stages of the storm. At a
      second field site (stormwater retention pond), RAPD-PCR profiling showed that the
      viral community of the pond changed dramatically over the course of two intense
      storms while relatively little change was observed over similar time scales in
      the absence of disturbance. Comparisons of planktonic and particle-associated
      viral communities revealed two completely distinct communities, suggesting that
      particle-associated viruses represent a potentially large and overlooked portion
      of aquatic viral abundance and diversity. Our findings show that stormwater
      runoff can quickly change the composition of freshwater microbial communities.
      Based on these findings, increased storms in the coastal mid-Atlantic region
      predicted by most climate change models will likely have important impacts on the
      structure and function of local freshwater microbial communities. 

PMID- 24672518
TI  - The microRNAs as potential biomarkers for predicting the onset of aflatoxin
      exposure in human beings: a review.
AB  - The identification of aflatoxins as human carcinogens has stimulated extensive
      research efforts, which continue to the present, to assess potential health
      hazards resulting from contamination of the human food supply and to minimize
      exposure. The use of biomarkers that are mechanistically supported by
      toxicological studies will be important tools for identifying stages in the
      progression of development of the health effects of environmental agents. miRNAs
      are small non-coding mRNAs that regulate post-transcriptional gene expression.
      Also, they are molecular markers of cellular responses to various chemical
      agents. Growing evidence has demonstrated that environmental chemicals can induce
      changes in miRNA expression. miRNAs are good biomarkers because they are well
      defined, chemically uniform, restricted to a manageable number of species, and
      stable in cells and in the circulation. miRNAs have been used as serological
      markers of HCC and other tumors. The expression patterns of different miRNAs can
      distinguish among HCC-hepatitis viruses related, HCC cirrhosis-derivate, and HCC
      unrelated to either of them. The main objective of this review is to find
      unreported miRNAs in HCC related to other causes, so that they can be used as
      specific molecular biomarkers in populations exposed to aflatoxins and as early
      markers of exposure, damage/presence of HCC. Until today specific miRNAs as
      markers for aflatoxins-exposure and their reliability are currently lacking.
      Based on their elucidated mechanisms of action, potential miRNAs that could serve
      as possible markers of HCC by exposure to aflatoxins are miR-27a, miR-27b, miR
      122, miR-148, miR-155, miR-192, miR-214, miR-221, miR-429, and miR-500. Future
      validation for all of these miRNAs will be needed to assess their prognostic
      significance and confirm their relationship with the induction of HCC due to
      aflatoxin exposure. 

PMID- 24672521
TI  - New vaccines for Mammalian allergy using molecular approaches.
AB  - Allergen-specific immunotherapy (SIT) offers a disease specific causative
      treatment by modifying the allergen-specific immune response allowing tolerance
      to higher doses of allergen and preventing progression of allergic diseases. It
      may be considered in patients allergic to furry animals. Current mammalian
      allergy vaccines are still prepared from relatively poorly defined allergen
      extracts and may induce immediate and late phase side effects. Although the
      mechanisms of SIT are still not fully understood, the more recent approaches
      report different strategies to reduce both allergen-specific IgE as well as T
      cell reactivity. The availability of recombinant allergens and synthetic peptides
      from the mammalian species has contributed to formulating new allergy vaccines to
      improve SIT for furry animal allergy. The majority of studies have focused on the
      major cat allergen Fel d 1 due to its extensive characterization in terms of IgE
      and T cell epitopes and to its dominant role in cat allergy. Here we review the
      most recent approaches, e.g., synthetic peptides, recombinant allergen
      derivatives, different hypoallergenic molecules, and recombinant allergens
      coupled to virus-like particles or immunomodulatory substances as well as
      strategies targeting the allergen to Fcgamma receptors and the MHC class II
      pathway using a new route for administration. Many of the new vaccines hold
      promise but only a few of them have been investigated in clinical trials which
      will be the gold standard for evaluation of safety and efficacy in allergic
      patients. 

PMID- 24672523
TI  - DAMP-Mediated Activation of NLRP3-Inflammasome in Brain Sterile Inflammation: The
      Fine Line between Healing and Neurodegeneration.

PMID- 24672522
TI  - Improving the outcome of leukemia by natural killer cell-based immunotherapeutic
      strategies.
AB  - Blurring the boundary between innate and adaptive immune system, natural killer
      (NK) cells are widely recognized as potent anti-leukemia mediators. Alloreactive
      donor NK cells have been shown to improve the outcome of allogeneic stem-cell
      transplantation for leukemia. In addition, in vivo transfer of NK cells may soon
      reveal an important therapeutic tool for leukemia, if tolerance to NK-mediated
      anti-leukemia effects is overcome. This will require, at a minimum, the ex vivo
      generation of a clinically safe NK cell product containing adequate numbers of NK
      cells with robust anti-leukemia potential. Ideally, ex vivo generated NK cells
      should also have similar anti-leukemia potential in different patients, and be
      easy to obtain for convenient clinical scale-up. Moreover, optimal clinical
      protocols for NK therapy in leukemia and other cancers are still lacking. These
      and other issues are being currently addressed by multiple research groups. This
      review will first describe current laboratory NK cell expansion and
      differentiation techniques by separately addressing different NK cell sources.
      Subsequently, it will address the mechanisms known to be responsible for NK cell
      alloreactivity, as well as their clinical impact in the hematopoietic stem cells
      transplantation setting. Finally, it will briefly provide insight on past NK
      based clinical trials. 

PMID- 24672524
TI  - Radiation for Awakening the Dormant Immune System, a Promising Challenge to be
      Explored.
AB  - Recent advances that have been made in our understanding of cancer biology and
      immunology show that infiltrated immune cells and cytokines in the tumor
      microenvironment may play different functions that appear tightly related to
      clinical outcomes. Strategies aimed at interfering with the cross-talk between
      microenvironment tumor cells and their cellular partners have been considered for
      the development of new immunotherapies. These novel therapies target different
      cell components of the tumor microenvironment and importantly, they may be
      coupled and boosted with classical treatments, such as radiotherapy. In this
      work, we try to summarize recent data on the microenvironment impact of radiation
      therapy, from pre-clinical research to the clinic, while taking into account that
      this new knowledge will probably translate into indication and objective of
      radiation therapy changes in the next future. 

PMID- 24672525
TI  - Exosomes in the gut.

PMID- 24672526
TI  - Definition of a Family of Tissue-Protective Cytokines Using Functional Cluster
      Analysis: A Proof-of-Concept Study.
AB  - The discovery of the tissue-protective activities of erythropoietin (EPO) has
      underlined the importance of some cytokines in tissue-protection, repair, and
      remodeling. As such activities have been reported for other cytokines, we asked
      whether we could define a class of tissue-protective cytokines. We therefore
      explored a novel approach based on functional clustering. In this pilot study, we
      started by analyzing a small number of cytokines (30). We functionally classified
      the 30 cytokines according to their interactions by using the bioinformatics tool
      STRING (Search Tool for the Retrieval of Interacting Genes), followed by
      hierarchical cluster analysis. The results of this functional clustering were
      different from those obtained by clustering cytokines simply according to their
      sequence. We previously reported that the protective activity of EPO in a model
      of cerebral ischemia was paralleled by an upregulation of synaptic plasticity
      genes, particularly early growth response 2 (EGR2). To assess the predictivity of
      functional clustering, we tested some of the cytokines clustering close to EPO
      (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF;
      thrombopoietin, THPO) in an in vitro model of human neuronal cells for their
      ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression.
      Although these data would need to be extended to a larger number of cytokines and
      the biological validation should be done using more robust in vivo models, rather
      then just one cell line, this study shows the feasibility of this approach. This
      type of functional cluster analysis could be extended to other fields of cytokine
      research and help design biological experiments. 

PMID- 24672528
TI  - Understanding the intracellular trafficking and intercellular transport of
      potexviruses in their host plants.
AB  - The movement of potexviruses through the cytoplasm to plasmodesmata (PD) and
      through PD to adjacent cells depends on the viral and host cellular proteins.
      Potexviruses encode three movement proteins [referred to as the triple gene block
      (TGB1-3)]. TGB1 protein moves cell-to-cell through PD and requires TGB2 and TGB3,
      which are endoplasmic reticulum (ER)-located proteins. TGB3 protein directs the
      movement of the ER-derived vesicles induced by TGB2 protein from the perinuclear
      ER to the cortical ER. TGB2 protein physically interacts with TGB3 protein in a
      membrane-associated form and also interacts with either coat protein (CP) or TGB1
      protein at the ER network. Recent studies indicate that potexvirus movement
      involves the interaction between TGB proteins and CP with host proteins including
      membrane rafts. A group of host cellular membrane raft proteins, remorins, can
      serve as a counteracting membrane platform for viral ribonucleoprotein (RNP)
      docking and can thereby inhibit viral movement. The CP, which is a component of
      the RNP movement complex, is also critical for viral cell-to-cell movement
      through the PD. Interactions between TGB1 protein and/or the CP subunit with the
      5'-terminus of genomic RNA [viral RNA (vRNA)] form RNP movement complexes and
      direct the movement of vRNAs through the PD. Recent studies show that tobacco
      proteins such as NbMPB2C or NbDnaJ-like proteins interact with the stem-loop 1
      RNA located at the 5'-terminus of Potato virus X vRNA and regulate intracellular
      as well as intercellular movement. Although several host proteins that interact
      with vRNAs or viral proteins and that are crucial for vRNA transport have been
      screened and characterized, additional host proteins and details of viral
      movement remain to be characterized. In this review, we describe recent progress
      in understanding potexvirus movement within and between cells and how such
      movement is affected by interactions between vRNA/proteins and host proteins. 

PMID- 24672529
TI  - Lignin, mitochondrial family, and photorespiratory transporter classification as
      case studies in using co-expression, co-response, and protein locations to aid in
      identifying transport functions.
AB  - Whole genome sequencing and the relative ease of transcript profiling have
      facilitated the collection and data warehousing of immense quantities of
      expression data. However, a substantial proportion of genes are not yet
      functionally annotated a problem which is particularly acute for transport
      proteins. In Arabidopsis, for example, only a minor fraction of the estimated 700
      intracellular transporters have been identified at the molecular genetic level.
      Furthermore it is only within the last couple of years that critical genes such
      as those encoding the final transport step required for the long distance
      transport of sucrose and the first transporter of the core photorespiratory
      pathway have been identified. Here we will describe how transcriptional
      coordination between genes of known function and non-annotated genes allows the
      identification of putative transporters on the premise that such co-expressed
      genes tend to be functionally related. We will additionally extend this to
      include the expansion of this approach to include phenotypic information from
      other levels of cellular organization such as proteomic and metabolomic data and
      provide case studies wherein this approach has successfully been used to fill
      knowledge gaps in important metabolic pathways and physiological processes. 

PMID- 24672527
TI  - Autoimmunity as a double agent in tumor killing and cancer promotion.
AB  - Cancer immunotherapy through manipulation of the immune system holds great
      potential for the treatment of human cancers. However, recent trials targeting
      the negative immune regulators cytotoxic T-lymphocyte antigen 4, programed death
      1 (PD-1), and PD-1 receptor ligand (PD-L1) demonstrated that clinically
      significant antitumor responses were often associated with the induction of
      autoimmune toxicity. This finding suggests that the same immune mechanisms that
      elicit autoimmunity may also contribute to the destruction of tumors. Given the
      fact that the immunological identity of tumors might be largely an
      immunoprivileged self, autoimmunity may not represent a wholly undesirable
      outcome in the context of cancer immunotherapy. Rather, targeted killing of
      cancer cells and autoimmune damage to healthy tissues may be intricately linked
      through molecular mechanisms, in particular inflammatory cytokine signaling. On
      the other hand, since chronic inflammation is a well-recognized condition that
      promotes tumor development, it appears that autoimmunity can be a "double agent"
      in mediating either pro-tumor or antitumor effects. This review surveys the tumor
      promoting and tumoricidal activities of several prominent cytokines: IFN-gamma,
      TNF-alpha, TGF-beta, IL-17, IL-23, IL-4, and IL-13, produced by three major
      subsets of T helper cells that interact with innate immune cells. Many of these
      cytokines exert divergent and seemingly contradictory effects on cancer
      development in different human and animal models, suggesting a high degree of
      context dependence in their functions. We hypothesize that these inflammatory
      cytokines could mediate a feedback loop of autoimmunity, antitumor immunity, and
      tumorigenesis. Understanding the diverse and paradoxical roles of cytokines from
      autoimmune responses in the setting of cancer will advance the long-term goal of
      improving cancer immunotherapy, while minimizing the hazards of immune-mediated
      tissue damage and the possibility of de novo tumorigenesis, through proper
      monitoring and preventive measures. 

PMID- 24672530
TI  - Plasma membrane lipid-protein interactions affect signaling processes in sterol
      biosynthesis mutants in Arabidopsis thaliana.
AB  - The plasma membrane is an important organelle providing structure, signaling and
      transport as major biological functions. Being composed of lipids and proteins
      with different physicochemical properties, the biological functions of membranes
      depend on specific protein-protein and protein-lipid interactions. Interactions
      of proteins with their specific sterol and lipid environment were shown to be
      important factors for protein recruitment into sub-compartmental structures of
      the plasma membrane. System-wide implications of altered endogenous sterol levels
      for membrane functions in living cells were not studied in higher plant cells. In
      particular, little is known how alterations in membrane sterol composition affect
      protein and lipid organization and interaction within membranes. Here, we
      conducted a comparative analysis of the plasma membrane protein and lipid
      composition in Arabidopsis sterol-biosynthesis mutants smt1 and ugt80A2;B1. smt1
      shows general alterations in sterol composition while ugt80A2;B1 is significantly
      impaired in sterol glycosylation. By systematically analyzing different cellular
      fractions and combining proteomic with lipidomic data we were able to reveal
      contrasting alterations in lipid-protein interactions in both mutants, with
      resulting differential changes in plasma membrane signaling status. 

PMID- 24672531
TI  - Overview of the functional virulent genome of the coffee leaf rust pathogen
      Hemileia vastatrix with an emphasis on early stages of infection.
AB  - Hemileia vastatrix is the causal agent of coffee leaf rust, the most important
      disease of coffee Arabica. In this work, a 454-pyrosequencing transcriptome
      analysis of H. vastatrix germinating urediniospores (gU) and appressoria (Ap) was
      performed and compared to previously published in planta haustoria-rich (H) data.
      A total of 9234 transcripts were identified and annotated. Ca. 50% of these
      transcripts showed no significant homology to international databases. Only 784
      sequences were shared by the three conditions, and 75% were exclusive of either
      gU (2146), Ap (1479) or H (3270). Relative transcript abundance and RT-qPCR
      analyses for a selection of genes indicated a particularly active metabolism,
      translational activity and production of new structures in the appressoria and
      intense signaling, transport, secretory activity and cellular multiplication in
      the germinating urediniospores, suggesting the onset of a plant-fungus dialogue
      as early as at the germ tube stage. Gene expression related to the production of
      carbohydrate-active enzymes and accumulation of glycerol in germinating
      urediniospores and appressoria suggests that combined lytic and physical
      mechanisms are involved in appressoria-mediated penetration. Besides contributing
      to the characterization of molecular processes leading to appressoria-mediated
      infection by rust fungi, these results point toward the identification of new H.
      vastatrix candidate virulence factors, with 516 genes predicted to encode
      secreted proteins. 

PMID- 24672532
TI  - Thermospermine modulates expression of auxin-related genes in Arabidopsis.
AB  - Thermospermine, a structural isomer of spermine, is widely distributed in the
      plant kingdom and has been shown to play a role in repressing xylem
      differentiation by studies of its deficient mutant, acaulis5 (acl5), in
      Arabidopsis. Our results of microarray and real-time PCR analyses revealed that,
      in addition to a number of genes involved in xylem differentiation, genes related
      to auxin signaling were up-regulated in acl5 seedlings. These genes include
      MONOPTEROS, an auxin response factor gene, which acts as a master switch for
      auxin-dependent procambium formation, and its target genes. Their expression was
      reduced by exogenous treatment with thermospermine or by transgenic induction of
      the ACL5 gene. We examined the effect of synthetic polyamines on the expression
      of these auxin-related genes and on the vascular phenotype of acl5, and found
      that tetramines containing the NC3NC3N chain could mimic the effect of
      thermospermine but longer polyamines containing the same chain had little or no
      such effect. We also found that thermospermine had an inhibitory effect on
      lateral root formation in wild-type seedlings and it was mimicked by synthetic
      tetramines with the NC3NC3N chain. These results suggest the importance of the
      NC3NC3N chain of thermospermine in its action in modulating auxin signaling. 

PMID- 24672534
TI  - Leaf metabolite profile of the Brazilian resurrection plant Barbacenia purpurea
      Hook. (Velloziaceae) shows two time-dependent responses during desiccation and
      recovering.
AB  - Barbacenia purpurea is a resurrection species endemic to rock outcrops, in Rio de
      Janeiro, Brazil. It tolerates great temperature variations, which are associated
      to periods of up to 30 days without precipitation. Using a metabolomic approach,
      we analyzed, under winter and summer conditions, changes in the leaf metabolite
      profile (MP) of potted plants of B. purpurea submitted to daily watered and water
      deficit for at least 20 days and subsequent slow rehydration for 5 days. Leaves
      were collected at different time points and had their MP analyzed by GC/MS,
      HPAEC, and UHPLC techniques, allowing the identification of more than 60
      different compounds, including organic and amino acids, sugars, and polyols,
      among others. In the winter experiment, results suggest the presence of two time
      dependent responses in B. purpurea under water stress. The first one starts with
      the increase in the content of caffeoyl-quinic acids, substances with strong
      antioxidant activity, until the 16th day of water suppression. When RWC reached
      less than 80 and 70%, in winter and summer respectively, it was observed an
      increase in polyols and monosaccharides, followed by an increment in the content
      of RFO, suggesting osmotic adjustment. Amino acids, such as GABA and asparagine,
      also increased due to 16 days of water suppression. During rehydration, the
      levels of the mentioned compounds became similar to those found at the beginning
      of the experiment and when compared to daily watered plants. We conclude that the
      tolerance of B. purpurea to dehydration involves the perception of water deficit
      intensity, which seems to result in different strategies to overcome the gradient
      of water availability imposed along a certain period of stress mainly during
      winter. Data from summer experiment indicate that the metabolism of B. pupurea
      was already primed for drought stress. The accumulation of phenolics in summer
      seemed to be more temperature and irradiance-dependent than on the RWC. 

PMID- 24672533
TI  - Physiological and molecular implications of plant polyamine metabolism during
      biotic interactions.
AB  - During ontogeny, plants interact with a wide variety of microorganisms. The
      association with mutualistic microbes results in benefits for the plant. By
      contrast, pathogens may cause a remarkable impairment of plant growth and
      development. Both types of plant-microbe interactions provoke notable changes in
      the polyamine (PA) metabolism of the host and/or the microbe, being each
      interaction a complex and dynamic process. It has been well documented that the
      levels of free and conjugated PAs undergo profound changes in plant tissues
      during the interaction with microorganisms. In general, this is correlated with a
      precise and coordinated regulation of PA biosynthetic and catabolic enzymes.
      Interestingly, some evidence suggests that the relative importance of these
      metabolic pathways may depend on the nature of the microorganism, a concept that
      stems from the fact that these amines mediate the activation of plant defense
      mechanisms. This effect is mediated mostly through PA oxidation, even though part
      of the response is activated by non-oxidized PAs. In the last years, a great deal
      of effort has been devoted to profile plant gene expression following
      microorganism recognition. In addition, the phenotypes of transgenic and mutant
      plants in PA metabolism genes have been assessed. In this review, we integrate
      the current knowledge on this field and analyze the possible roles of these
      amines during the interaction of plants with microbes. 

PMID- 24672535
TI  - Functional implications of peroxisomal nitric oxide (NO) in plants.

PMID- 24672536
TI  - Cell wall methanol as a signal in plant immunity.
AB  - Cell wall pectin forms a matrix around the cellulose-xyloglucan network that is
      composed of rhamnogalacturonan I, rhamnogalacturonan II, and homogalacturonan
      (HG), a major pectic polymer consisting of alpha-1,4-linked galacturonic acids.
      HG is secreted in a highly methyl-esterified form and selectively de-methyl
      esterified by pectin methylesterases (PMEs) during cell growth and pathogen
      attack. The mechanical damage that often precedes the penetration of the leaf by
      a pathogen promotes the activation of PME, which in turn leads to the emission of
      methanol (MeOH), an abundant volatile organic compound, which is quickly
      perceived by the intact leaves of the damaged plant, and the neighboring plants.
      The exposure to MeOH may result in a "priming" effect on intact leaves, setting
      the stage for the within-plant, and neighboring plant immunity. The emission of
      MeOH by a wounded plant enhances the resistance of the non-wounded, neighboring
      "receiver" plants to bacterial pathogens and promotes cell-to-cell communication
      that facilitates the spread of viruses in neighboring plants. 

PMID- 24672537
TI  - Copy number variation analysis in the context of electronic medical records and
      large-scale genomics consortium efforts.
AB  - The goal of this paper is to review recent research on copy number variations
      (CNVs) and their association with complex and rare diseases. In the latter part
      of this paper, we focus on how large biorepositories such as the electronic
      medical record and genomics (eMERGE) consortium may be best leveraged to
      systematically mine for potentially pathogenic CNVs, and we end with a discussion
      of how such variants might be reported back for inclusion in electronic medical
      records as part of medical history. 

PMID- 24672538
TI  - VTET: a variable threshold exact test for identifying disease-associated copy
      number variations enriched in short genomic regions.
AB  - Copy number variations (CNVs) constitute a major source of genetic variations in
      human populations and have been reported to be associated with complex diseases.
      Methods have been developed for detecting CNVs and testing CNV associations in
      genome-wide association studies (GWAS) based on SNP arrays. Commonly used two
      step testing procedures work well only for long CNVs while direct CNV association
      testing methods work only for recurrent CNVs. Assuming that short CNVs disrupting
      any part of a given genomic region increase disease risk, we developed a variable
      threshold exact test (VTET) for testing disease associations of CNVs randomly
      distributed in the genome using intensity data from SNP arrays. By extensive
      simulations, we found that VTET outperformed two-step testing procedures based on
      existing CNV calling algorithms for short CNVs and that the performance of VTET
      was robust to the length of the genomic region. In addition, VTET had a
      comparable performance with CNVtools for testing the association of recurrent
      CNVs. Thus, we expect VTET to be useful for testing disease associations of both
      recurrent and randomly distributed CNVs using existing GWAS data. We applied VTET
      to a lung cancer GWAS and identified a genome-wide significant region on
      chromosome 18q22.3 for lung squamous cell carcinoma. 

PMID- 24672540
TI  - The anatomy of a weight recidivism and revision bariatric surgical clinic.
AB  - Abstract. Weight recidivism in bariatric surgery failure is multifactorial. It
      ranges from inappropriate patient selection for primary surgery to
      technical/anatomic issues related to the original surgery. Most bariatric
      surgeons and centers focus on primary bariatric surgery while weight recidivism
      and its complications are very much secondary concerns. Methods. We report on our
      initial experience having established a dedicated weight recidivism and
      revisional bariatric surgery clinic. A single surgeon, dedicated nursing,
      dieticians, and psychologist developed care maps, goals of care, nonsurgical
      candidate rules, and discharge planning strategies. Results. A single year audit
      (2012) of clinical activity revealed 137 patients, with a mean age 49 +/- 10.1
      years (6 years older on average than in our primary clinic), 75% of whom were
      women with BMI 47 +/- 11.5. Over three quarters had undergone a vertical band
      gastroplasty while 15% had had a laparoscopic adjustable gastric band. Only 27%
      of those attending clinic required further surgery. As for primary surgery, the
      role of the obesity expert clinical psychologist was a key component to achieving
      successful revision outcomes. Conclusion. With an exponential rise in obesity and
      a concomitant major increase in bariatric surgery, an inevitable increase in
      revisional surgery is becoming a reality. Anticipating this increase in activity,
      Alberta Health Services, Alberta, Canada, has established a unique and dedicated
      clinic whose early results are promising. 

PMID- 24672539
TI  - miRNA dysregulation in cancer: towards a mechanistic understanding.
AB  - It is now well known that gene expression is intricately regulated inside each
      cell especially in mammals. There are multiple layers of gene regulation active
      inside a cell at a given point of time. Gene expression is regulated post
      transcriptionally by microRNAs and other factors. Mechanistically, microRNAs are
      known to bind to the 3' UTR of mRNAs and cause repression of gene expression and
      the number of known microRNAs continues to increase every day. Dysregulated
      microRNA signatures in different types of cancer are being uncovered consistently
      implying their importance in cellular homeostasis. However when studied in
      isolation in mouse models, clear-cut cellular and molecular mechanisms have been
      described only for a select few microRNAs. What is the reason behind this
      discrepancy? Are microRNAs small players in gene regulation helping only to fine
      tune gene expression? Or are their roles tissue and cell type-specific with
      single-cell level effects on mRNA expression and microRNA threshold levels? Or
      does it all come down to the technical limitations of high-throughput techniques,
      resulting in false positive results? In this review, we will assess the
      challenges facing the field and potential avenues for resolving the cellular and
      molecular mechanisms of these small but important regulators of gene expression. 

PMID- 24672541
TI  - Characteristics of metachronous gastric tumors after endoscopic submucosal
      dissection for gastric intraepithelial neoplasms.
AB  - Background. Recently, endoscopic submucosal dissection (ESD) has become a
      standard treatment method for early gastric cancer and concurrent stomach
      preservation. However, metachronous recurrences have become a major problem. We
      evaluated the incidence and clinicopathologic features of and examined the risk
      factors for metachronous gastric tumors. Methods. A total of 357 patients who
      underwent ESD for gastric tumors (245 early gastric cancers and 112 adenomas) and
      were followed up for more than 12 months without recurrence within the first 12
      months were enrolled. We investigated the incidence and clinicopathologic
      features of metachronous tumors after ESD. We also analyzed the potential risk
      factors for metachronous tumors using the Kaplan-Meier method and Cox's
      proportional hazards model. Results. The annual incidence of metachronous tumors
      after ESD was 2.4%. The median period until discovery after initial ESD was 26.0
      months, and the median observation period was 52.6 months. Male patients
      developed metachronous tumors more frequently (P = 0.04), and the hazard ratio of
      female to male patients was 0.36 (95% confidence interval: 0.11-0.89).
      Conclusions. Patients with a previous history of gastric tumors have a high risk
      of subsequent gastric tumor development and male patients should be carefully
      followed up after ESD for gastric tumor. 

PMID- 24672542
TI  - Prediction of optimal reversal dose of sugammadex after rocuronium administration
      in adult surgical patients.
AB  - The objective of this study was to determine the point after sugammadex
      administration at which sufficient or insufficient dose could be determined,
      using first twitch height of train-of-four (T1 height) or train-of-four ratio
      (TOFR) as indicators. Groups A and B received 1 mg/kg and 0.5 mg/kg of
      sugammadex, respectively, as a first dose when the second twitch reappeared in
      train-of-four stimulation, and Groups C and D received 1 mg/kg and 0.5 mg/kg of
      sugammadex, respectively, as the first dose at posttetanic counts 1-3. Five
      minutes after the first dose, an additional 1 mg/kg of sugammadex was
      administered and changes in T1 height and TOFR were observed. Patients were
      divided into a recovered group and a partly recovered group, based on percentage
      changes in T1 height after additional dosing. T1 height and TOFR during the 5 min
      after first dose were then compared. In the recovered group, TOFR exceeded 90% in
      all patients at 3 min after sugammadex administration. In the partly recovered
      group, none of the patients had a TOFR above 90% at 3 min after sugammadex
      administration. An additional dose of sugammadex can be considered unnecessary if
      the train-of-four ratio is >=90% at 3 min after sugammadex administration. This
      trial is registered with UMIN000007245. 

PMID- 24672543
TI  - Relationship between Metabolic Syndrome and Its Components with Psychological
      Distress.
AB  - Background. Metabolic syndrome (MetS) and psychological distress are hypothesized
      to have a bidirectional relationship. According to their high prevalence in most
      populations, appraisal of this theory would be of great clinical and research
      interest. Methods. Data were available as part of the Isfahan Healthy Heart
      Program (IHHP). A total of 9553 men and women aged >=19 years from three counties
      in central Iran were selected. Measurements consisted of serologic tests,
      anthropometrics, and self-reported 12-item general health questionnaire. Logistic
      regression analysis was used to find the association between MetS, MetS
      components, and distress level. Results. The mean age of 9553 participants (50%
      male) was 38.7 +/- 15.8 years. After adjusting for demographic factors, MetS (OR
      = 1.25, 95% CI: 1.01-1.37), central obesity (OR = 1.40, 95% CI: 1.15-1.49), and
      hypertension (OR = 1.55, 95% CI: 1.42-1.70) were associated with high distress
      level. However, after adding smoking status and low-density lipoprotein
      cholesterol to the adjustment factors, hypertension (OR = 1.79, 95% CI: 1.53
      1.98) and central obesity (OR = 1.41, 95% CI: 1.17-1.55), but not the MetS,
      remained significantly associated with distress level. Conclusion. The presence
      of association between the MetS as well as its key components and high distress
      level signifies the importance of integrating psychological assessment and
      intervention in the standard management of MetS patients. 

PMID- 24672544
TI  - Meta-analysis: overweight, obesity, and Parkinson's disease.
AB  - Objective. Parkinson's disease (PD) is a severe neurological disease and its risk
      factors remain largely unknown. A meta-analysis was carried out to investigate
      the relationship of overweight and obesity with PD. Methods. We used PubMed,
      EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) databases to
      identify studies of associations between overweight/obesity and PD. Overweight,
      obesity, and PD were used as keywords, and published works were retrieved until
      September 30, 2013. The extracted data were classified (BMI >= 30, 25 <= BMI <
      30, and BMI < 25) according to BMI values and analyzed using RevMan5.2 and
      Stata11.0. Results. Four cohort studies and three case-control studies were used
      to evaluate the association between overweight/obesity and PD, including 2857 PD
      patients and 5, 683, 939 cases of non-PD controls. There was a statistically
      significant difference between 25 <= BMI < 30  and BMI < 25 in the cohort study
      (RR = 1.17, 95% CI, 1.03-1.32,  P = 0.03), but there was no difference between
      BMI >= 30  and BMI < 25 or BMI >= 30  and 25 <= BMI < 30, where the respective RR
      was 1.16 and 0.84; the respective 95% CI was 0.67-2.01 and 0.61-1.15,
      respectively, and the P values were 0.60 and 0.28, respectively. Case-control
      studies showed that there was no statistical difference between any two groups.
      Conclusion. Meta-analysis showed that overweight might be a potential risk factor
      of PD. Demonstration of a causal role of overweight/obesity in PD development
      could have important therapeutic implications. 

PMID- 24672545
TI  - Resveratrol Prevention of Diabetic Nephropathy Is Associated with the Suppression
      of Renal Inflammation and Mesangial Cell Proliferation: Possible Roles of Akt/NF
      kappaB Pathway.
AB  - The present study was to investigate the protection of resveratrol (RSV) in
      diabetes associated with kidney inflammation and cell proliferation. Rat
      mesangial cell and streptozotocin-induced type 1 diabetes mouse model were used.
      In vitro, RSV attenuated high glucose-induced plasminogen activator inhibitor
      (PAI-1) expression and mesangial cell proliferation, as well as Akt and nuclear
      factor-kappa B (NF- kappa B) activation. The similar results were recaptured in
      the experiment with Akt inhibitors. In vivo, mice were divided into three groups:
      control group, diabetes mellitus (DM) group, and RSV-treated DM group. Compared
      with control group, the kidney weight to body weight ratio and albumin to
      creatinine ratio were increased in DM group, but not in RSV-treated DM group.
      Furthermore, the increased expression of PAI-1 and intercellular adhesion
      molecule-1 in diabetic renal cortex were also reduced by RSV administration.
      Besides, the kidney p-Akt/Akt ratio and NF- kappa B were significantly increased
      in DM group; however, these changes were reversed in RSV-treated DM group.
      Additionally, immunohistochemistry results indicated that RSV treatment reduced
      the density of proliferating cell nuclear antigen-positive cells significantly in
      glomeruli of diabetic mice. These results suggest that RSV prevents diabetes
      induced renal inflammation and mesangial cell proliferation possibly through
      Akt/NF- kappa B pathway inhibition. 

PMID- 24672546
TI  - Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the
      Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley
      Rats: A Biochemical, Metabolic, and Redox Approach.
AB  - The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular
      disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or
      mineral deficiency have been associated with Metabolic Syndrome development. This
      study aimed to investigate the effects of 8 weeks consumption of a hypersaline
      sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley
      rats (Metabolic Syndrome animal model). The ingestion of the mineral water (rich
      in sodium bicarbonate and with higher potassium, calcium, and magnesium content
      than the tap water used as control) reduced/prevented not only the fructose
      induced increase of heart rate, plasma triacylglycerols, insulin and leptin
      levels, hepatic catalase activity, and organ weight to body weight ratios (for
      liver and both kidneys) but also the decrease of hepatic glutathione peroxidase
      activity and oxidized glutathione content. This mineral-rich water seems to have
      potential to prevent Metabolic Syndrome induction by fructose. We hypothesize
      that its regular intake in the context of modern diets, which have a general
      acidic character interfering with mineral homeostasis and are poor in
      micronutrients, namely potassium, calcium, and magnesium, could add surplus value
      and attenuate imbalances, thus contributing to metabolic and redox health and,
      consequently, decreasing the risk for atherosclerotic cardiovascular disease. 

PMID- 24672547
TI  - Sexual well-being in adult male patients with congenital adrenal hyperplasia.
AB  - Introduction. Men with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency show impaired fecundity due to testicular adrenal rest tumors and/or
      suppression of the gonadal axis. Sexual well-being might be an additional factor;
      however, no data exists. Patients and Methods. Prospective longitudinal
      monocentric study included 20 male CAH patients (14 salt wasting, 6 simple
      virilizing; age 18-49 yr). Clinical assessment, testicular ultrasound,
      biochemical and hormonal parameters, three validated self-assessment
      questionnaires (SF-36, GBB-24, and HADS), and male Brief Sexual Function
      Inventory (BSFI) were analyzed at baseline and after two years. Results. Basal LH
      and testosterone levels suggested normal testicular function. LH and FSH
      responses to GnRH were more pronounced in patients with a good therapy control
      according to androstenedione/testosterone ratio < 0.2. This group had significant
      higher percentage of patients on dexamethasone medication. GBB-24, HADS, and SF
      36 showed impaired z-scores and no changes at follow-up. BSFI revealed
      impairments in dimensions "sexual drive," "erections," and "ejaculations,"
      whereas "problem assessment" and "overall satisfaction" revealed normal z-scores.
      Androstenedione levels correlated (P = 0.036) inversely with z-scores for "sexual
      drive" with higher levels associated with impaired "sexual drive." Conclusion.
      Male CAH patients showed a partly impaired sexual well-being which might be an
      additional factor for reduced fecundity. 

PMID- 24672548
TI  - Mandibular canine dimorphism in establishing sex identity in the lebanese
      population.
AB  - Background and Objective. In forensic investigations, mandibular canines provide
      excellent materials to identify gender since they are more likely to survive
      disasters. The objective of this study was to investigate gender dimorphism by
      comparing the mesiodistal width of mandibular permanent canines and intercanine
      distance in a group of Lebanese population. Methods. Participants consisted of
      undergraduate students from the School of Dentistry, Lebanese University, for two
      academic years who fulfilled the inclusion criteria. Canine widths and
      intercanine distance were measured by one operator directly on dental casts using
      a digital caliper. Results. One hundred thirty-three Lebanese dental students (54
      males and 69 females) aged 18-25 were included in the study. The intercanine
      distance was significantly greater in males (P value < 0.0001). The right and the
      left canine widths were significantly greater in males than in females (P value <
      0.0001). However, no significant difference was found between left and right
      canines for males (P value > 0.05) and females (P value > 0.05). The mean width
      of canine was greater than 7.188 mm for males. Conclusion. The parameters
      measured in the present study are of great help in sex identification in forensic
      investigations in the Lebanese adult population. 

PMID- 24672549
TI  - Four Derivative Spectrophotometric Methods for the Simultaneous Determination of
      Carmoisine and Ponceau 4R in Drinks and Comparison with High Performance Liquid
      Chromatography.
AB  - Four simple, rapid, and accurate spectrophotometric methods were developed for
      the simultaneous determination of two food colorants, Carmoisine (E122) and
      Ponceau 4R (E124), in their binary mixtures and soft drinks. The first method is
      based on recording the first derivative curves and determining each component
      using the zero-crossing technique. The second method uses the first derivative of
      ratio spectra. The ratio spectra are obtained by dividing the absorption spectra
      of the binary mixture by that of one of the components. The third method,
      derivative differential procedure, is based on the measurement of difference
      absorptivities derivatized in first order of solution of drink samples in 0,1 N
      NaOH relative to that of an equimolar solution in 0,1 N HCl at wavelengths of 366
      and 451 nm for Carmoisine and Ponceau 4R, respectively. The last method, based on
      the compensation method is presented for derivative spectrophotometric
      determination of E122 and E124 mixtures with overlapping spectra. By using ratios
      of the derivative maxima, the exact compensation of either component in the
      mixture can be achieved, followed by its determination. These proposed methods
      have been successfully applied to the binary mixtures and soft drinks and the
      results were statistically compared with the reference HPLC method (NMKL 130). 

PMID- 24672550
TI  - An Intimate Relationship between ROS and Insulin Signalling: Implications for
      Antioxidant Treatment of Fatty Liver Disease.
AB  - Oxidative stress damages multiple cellular components including DNA, lipids, and
      proteins and has been linked to pathological alterations in nonalcoholic fatty
      liver disease (NAFLD). Reactive oxygen species (ROS) emission, resulting from
      nutrient overload and mitochondrial dysfunction, is thought to be a principal
      mediator in NAFLD progression, particularly toward the development of hepatic
      insulin resistance. In the context of insulin signalling, ROS has a dual role, as
      both a facilitator and inhibitor of the insulin signalling cascade. ROS mediate
      these effects through redox modifications of cysteine residues affecting
      phosphatase enzyme activity, stress-sensitive kinases, and metabolic sensors.
      This review highlights the intricate relationship between redox-sensitive
      proteins and insulin signalling in the context of fatty liver disease, and to a
      larger extent, the importance of reactive oxygen species as primary signalling
      molecules in metabolically active cells. 

PMID- 24672552
TI  - Molecular and Technological Characterization of Saccharomyces cerevisiae Strains
      Isolated from Natural Fermentation of Susumaniello Grape Must in Apulia, Southern
      Italy.
AB  - The characterization of autochthonous Saccharomyces cerevisiae strains is an
      important step towards the conservation and employment of microbial biodiversity.
      The utilization of selected autochthonous yeast strains would be a powerful tool
      to enhance the organoleptic and sensory properties of typical regional wines. In
      fact, indigenous yeasts are better tailored to a particular must and because of
      this they are able to praise the peculiarities of the derived wine. The present
      study described the biodiversity of indigenous S. cerevisiae strains isolated
      from natural must fermentations of an ancient and recently rediscovered Apulian
      grape cultivar, denoted as "Susumaniello." The yeast strains denoted by the best
      oenological and technological features were identified and their fermentative
      performances were tested by either laboratory assay. Five yeast strains showed
      that they could be excellent candidates for the production of industrial starter
      cultures, since they dominated the fermentation process and produced wines
      characterized by peculiar oenological and organoleptic features. 

PMID- 24672551
TI  - 2-cys peroxiredoxins: emerging hubs determining redox dependency of Mammalian
      signaling networks.
AB  - Mammalian cells have a well-defined set of antioxidant enzymes, which includes
      superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins.
      Peroxiredoxins are the most recently identified family of antioxidant enzymes
      that catalyze the reduction reaction of peroxides, such as H2O2. In particular,
      typical 2-Cys peroxiredoxins are the featured peroxidase enzymes that receive the
      electrons from NADPH by coupling with thioredoxin and thioredoxin reductase.
      These enzymes distribute throughout the cellular compartments and, therefore, are
      thought to be broad-range antioxidant defenders. However, recent evidence
      demonstrates that typical 2-Cys peroxiredoxins play key signal regulatory roles
      in the various signaling networks by interacting with or residing near a specific
      redox-sensitive molecule. These discoveries help reveal the redox signaling
      landscape in mammalian cells and may further provide a new paradigm of
      therapeutic approaches based on redox signaling. 

PMID- 24672553
TI  - Contralateral ear occlusion for improving the reliability of otoacoustic emission
      screening tests.
AB  - Newborn hearing screening is an established healthcare standard in many countries
      and testing is feasible using otoacoustic emission (OAE) recording. It is well
      documented that OAEs can be suppressed by acoustic stimulation of the ear
      contralateral to the test ear. In clinical otoacoustic emission testing carried
      out in a sound attenuating booth, ambient noise levels are low such that the
      efferent system is not activated. However in newborn hearing screening, OAEs are
      often recorded in hospital or clinic environments, where ambient noise levels can
      be 60-70 dB SPL. Thus, results in the test ear can be influenced by ambient noise
      stimulating the opposite ear. Surprisingly, in hearing screening protocols there
      are no recommendations for avoiding contralateral suppression, that is,
      protecting the opposite ear from noise by blocking the ear canal. In the present
      study we have compared transient evoked and distortion product OAEs measured with
      and without contralateral ear plugging, in environmental settings with ambient
      noise levels <25 dB SPL, 45 dB SPL, and 55 dB SPL. We found out that without
      contralateral ear occlusion, ambient noise levels above 55 dB SPL can
      significantly attenuate OAE signals. We strongly suggest contralateral ear
      occlusion in OAE based hearing screening in noisy environments. 

PMID- 24672554
TI  - Demography and histologic pattern of laryngeal squamous cell carcinoma in kenya.
AB  - Background. Laryngeal squamous cell carcinoma is a common head and neck cancer
      worldwide. Objective. To determine the demographic characteristics of patients
      with laryngeal cancer, establish their tumor characteristics and relate it to
      their smoking and alcohol ingestion habits. Methods. Fifty cases and fifty
      controls were recruited of matching age, sex, and region of residence. History
      and pattern of cigarette smoking and alcohol ingestion was taken and analyzed.
      Results. 33 (66%) of the cases and 3 (6%) among controls were current cigarette
      smokers. 74% had smoked for more than 30 years, P < 0.0001 OR 21.3 (95% CI: 2.6
      176.1). There was a male predominance (96%) and most cases (62%) were from the
      ethnic communities in the highland areas of Kenya predominantly in Central and
      Eastern provinces. Very heavy drinkers had increased risk of P < 0.0001 OR, 6.0
      (95% CI: 1.957-18.398) and those who smoked cigarettes and drank alcohol had
      poorly differentiated tumors G3, P < 0.001, OR 11.652 (95% CI 2.305-58.895), and
      G4, P=0.52 OR 7.286 (95% CI 0.726-73.075). They also presented with advanced
      disease (73.6%). Conclusion. Cigarette smoking and alcohol ingestion are strong
      risk factors for development of late stage and poorly differentiated laryngeal
      squamous cell carcinoma in Kenya. 

PMID- 24672555
TI  - Long-Term Quantitative Biodistribution and Side Effects of Human Mesenchymal Stem
      Cells (hMSCs) Engraftment in NOD/SCID Mice following Irradiation.
AB  - There is little information on the fate of infused mesenchymal stem cells (MSCs)
      and long-term side effects after irradiation exposure. We addressed these
      questions using human MSCs (hMSCs) intravenously infused to nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice submitted to total body
      irradiation (TBI) or local irradiation (abdominal or leg irradiation). The
      animals were sacrificed 3 to 120 days after irradiation and the quantitative and
      spatial distribution of hMSCs were studied by polymerase chain reaction (PCR).
      Following their infusion into nonirradiated animals, hMSCs homed to various
      tissues. Engraftment depended on the dose of irradiation and the area exposed.
      Total body irradiation induced an increased hMSC engraftment level compared to
      nonirradiated mice, while local irradiations increased hMSC engraftment locally
      in the area of irradiation. Long-term engraftment of systemically administered
      hMSCs in NOD/SCID mice increased significantly in response to tissue injuries
      produced by local or total body irradiation until 2 weeks then slowly decreased
      depending on organs and the configuration of irradiation. In all cases, no tissue
      abnormality or abnormal hMSCs proliferation was observed at 120 days after
      irradiation. This work supports the safe and efficient use of MSCs by injection
      as an alternative approach in the short- and long-term treatment of severe
      complications after radiotherapy for patients refractory to conventional
      treatments. 

PMID- 24672556
TI  - 2-Year BMI Changes of Children Referred for Multidisciplinary Weight Management.
AB  - Objective. To examine body mass index (BMI) changes among pediatric
      multidisciplinary weight management participants and nonparticipants. Design. In
      this retrospective database analysis, we used multivariable mixed effect models
      to compare 2-year BMI z-score trajectories among 583 eligible overweight or obese
      children referred to the One Step Ahead program at the Boston Children's Primary
      Care Center between 2003 and 2009. Results. Of the referred children, 338 (58%)
      attended the program; 245 (42%) did not participate and were instead followed by
      their primary care providers within the group practice. The mean BMI z-score of
      program participants decreased modestly over a 2-year period and was lower than
      that of nonparticipants. The group-level difference in the rate of change in BMI
      z-score between participants and nonparticipants was statistically significant
      for 0-6 months (P = 0.001) and 19-24 months (P = 0.008); it was marginally
      significant for 13-18 months (P = 0.051) after referral. Younger participants (<5
      years) had better outcomes across all time periods examined. Conclusion. Children
      attending a multidisciplinary program experienced greater BMI z-score reductions
      compared with usual primary care in a real world practice; younger participants
      had significantly better outcomes. Future research should consider early
      intervention and cost-effectiveness analyses. 

PMID- 24672557
TI  - Effects of "vitex agnus castus" extract and magnesium supplementation, alone and
      in combination, on osteogenic and angiogenic factors and fracture healing in
      women with long bone fracture.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of the
      combination of vitex agnus castus extract, as a source of phytoestrogens, plus
      magnesium supplementation on osteogenic and angiogenic factors and callus
      formation in women with long bone fracture. MATERIAL AND METHODS: In a double
      blind randomized placebo controlled trial, 64 women with long bone fracture, 20
      45 years old, were randomly allocated to receive 1) one Agnugol tablet (4 mg
      dried fruit extract of vitex agnus castus) plus 250 mg magnesium oxide (VAC + Mg
      group (n = 10)), 2) one Agnugol tablet plus placebo (VAC group (n = 15)), 3)
      placebo plus 250 mg magnesium oxide (Mg group (n = 12)), or 4) placebo plus
      placebo (placebo group (n = 14)) per day for 8 weeks. At baseline and endpoint of
      the trial, serum alkaline phosphatase, osteocalcin, and vascular endothelial
      growth factor (VEGF) were measured together with radiological bone assessment.
      RESULTS: There were no significant differences in the characteristic aspects of
      concern between the four groups at baseline. Despite the increased level of
      alkaline phosphatase in the VAC group (188.33 +/- 16.27 to 240.40 +/- 21.49, P =
      0.05), administration of VAC + Mg could not increase alkaline phosphatase
      activity. However, treatment with VAC + Mg significantly enhanced the osteocalcin
      level. The serum concentration of VEGF was increased in the VAC group (269.04 +/-
      116.63 to 640.03 +/- 240.16, P < 0.05). Callus formation in the VAC + Mg group
      was higher than the other groups but the differences between the four groups were
      not significant (P = 0.39). No relevant side effect was observed in patients in
      each group. CONCLUSION: Our results suggest that administration of vitex agnus
      castus plus magnesium may promote fracture healing. However, more studies need to
      further explore the roles of vitex agnus castus in fracture repair processes.

PMID- 24672558
TI  - Comparative evaluation of the effects of hydroxyethyl starch on coagulation state
      of patients during brain tumor surgeries in comparison to crystalloids by
      thromboelastography.
AB  - BACKGROUND: Hypercoagulability has been reported in primary brain tumors which
      can lead to thrombotic complications. Hydroxyethyl starch (hetastarch) is a
      synthetic colloid solution with adverse effects on blood coagulation. The aim of
      this study was to evaluate the protective effect of hetastarch in reducing
      thromboembolic events in these patients. MATERIALS AND METHODS: In a double
      blinded clinical trial, 60 brain tumor surgery patients were randomly divided
      into two groups and given 10 mL/kg hetastarch or normal saline during surgery.
      Blood coagulation was compared before and after infusion of these fluids within
      and between groups by thromboelastography (TEG). RESULTS: There were no
      significant differences in bleeding (P = 0.126), duration of surgery (P = 0.504),
      and fluid intake (0.09L) between the two groups. Percentage of changes in R (R:
      Time to initiate fibrin formation), K (K: Measure of the speed taken to reach a
      specific level of clot strength), and Ly30 (Ly30: Percent of fibrin distraction
      after 30 minutes of clot formation) in the crystalloid group were -20.61 +/-
      26.46, -30.02 +/- 49.10, and 1.27 +/- 22.63, and that in the colloid group were
      22.10 +/- 26.11, 41.79 +/- 37.15, and 59.09 +/- 37.12, respectively.
      Deterioration in hemostasis during and after surgery was not observed.
      CONCLUSION: There was a reduction in the speed of clot formation and increase in
      clot lysis in the hetastarch group. Coagulability was decreased in the colloid
      group. Infusion of 10 mL/kg hetastarch in brain tumor resection surgeries can
      probably decrease susceptibility of these patients to deep vein thrombosis (DVT)
      and thromboembolic events.

PMID- 24672559
TI  - Metabolic syndrome in migraine headache: A case-control study.
AB  - BACKGROUND: The correlation of metabolic syndrome and migraine headache was
      evaluated in some previous studies. However there is no study that compared the
      prevalence of metabolic syndrome in the patients with and without migraine.
      Control of coincidental factors such as metabolic syndrome reduces therapeutic
      resistance in migrainous patients. The aim of this study was to compare
      prevalence of metabolic syndrome in patients with and without migraine headache.
      MATERIALS AND METHODS: 200 migrainous patients diagnosed according to
      International Headache Society and 200 healthy controls without migraine enrolled
      in this study. Metabolic syndrome was diagnosed according to ATP III criteria in
      these two groups and compared with each other. RESULTS: In this study, 17% (34)
      of migrainous patients and 15% (30) of healthy control without migraine had
      metabolic syndrome. (P = 0.585). Of the metabolic syndrome components, body mass
      index (P = 0.05) and waist circumference in migrainous (P = 0.03) were
      significantly more frequent. CONCLUSION: Our results demonstrate that metabolic
      syndrome and migraine headache had not significant correlation; however, higher
      body mass index and waist circumference as metabolic syndrome components had
      correlated with migraine headache.

PMID- 24672560
TI  - Serum levels of IL-17, IL-4, and INFgamma in Serbian patients with early
      rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory
      disease with autoimmune etiology, characterized by synovial inflammation and
      destruction of joint cartilage and bone. There are controversial data about the
      profile of interleukin-17 (IL-17A), interleukin-4 (IL-4), and interferon-gamma
      (INFgamma), indicating in some studies the key role of IL-17, while in others the
      Th1 cytokines. MATERIALS AND METHODS: Serum samples of 31 early RA patients were
      evaluated for erythrocytes sedimentation rate (ESR), rheumatoid factor (RF), C
      reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP),
      and for the tested cytokines (IL-17A, IL-4, and INFgamma). Disease activity score
      (DAS28) calculation was done for all patients. Control serum samples were
      obtained from 29 healthy volunteers. RESULTS: The levels of tested cytokines were
      significantly higher (IL-17A, p < 0.001; INFgamma, p < 0.001; IL-4, p < 0.01) in
      patients with early RA, compared to the healthy controls. In early RA patients, a
      strong correlation of serum IL-17A was found with DAS28, ESR, and CRP. Also,
      significant negative correlation was found between serum INFgamma levels and the
      DAS28 score, indicating that INFgamma may play a key role in maintaining immune
      homeostasis in patients with RA. CONCLUSION: The mean serum IL-17A levels in
      patients with early RA, corresponded with the disease activity and severity. This
      might highlight the usefulness of the serum IL-17A level in defining the activity
      and predictive patterns, for aggressive disease therapy, and it might express
      specific therapeutically targets.

PMID- 24672561
TI  - Ultrasound surface probe as a screening method for evaluating the patients with
      blunt abdominal trauma.
AB  - BACKGROUND: Blunt abdominal trauma is one of the causes of mortality in emergency
      department. Free fluid in the abdomen due to intra-abdominal blunt trauma can be
      determined by the surface probe of ultrasound. Since the importance of this free
      fluid in hemodynamic stable patients with blunt trauma is associated with the
      unknown outcome for surgeons, this study was performed to evaluate the role of
      ultrasound surface probe as a screening method in evaluating the patients with
      blunt abdominal trauma. MATERIALS AND METHODS: A descriptive-analytical study was
      done on 45 patients with blunt abdominal trauma and hemodynamic stability. The
      patients were evaluated twice during the three-hours, including repeated
      ultrasound surface probe and clinical examinations. Computerized tomography was
      also performed. The patients were divided based on the amount of the free fluid
      in the abdomen during the evaluations into two groups: Fixed or increased, and
      decreased free fluid. The results of the different evaluated methods were
      compared using the sensitivity and specificity. RESULTS: From 17 patients with CT
      abnormalities, free fluid increased in 14 patients (82.4%). Free fluid was
      decreased in three patients who were discharged well from the surgery service
      without any complication. Surface probe in prognosis detection had a sensitivity
      of 82.4% and specificity of 92.9%. The percentage of false positive and negative
      ultrasound compared with CT scan was 7.1% and 17.6%. Also, positive and negative
      predictive value of the ultrasound with surface probe was 87.5% and 89.7%
      respectively. CONCLUSION: The use of the ultrasound with surface probe in the
      diagnosis of free fluid in blunt abdominal trauma in hemodynamic stable patients
      can be considered as a useful screening method.

PMID- 24672562
TI  - The effect of vitamin A and vitamin C on postoperative adhesion formation: A rat
      model study.
AB  - BACKGROUND: The aim of this study is to investigate the effect of vitamin A and
      C, as the agents that improve wound healing, on the adhesion formation process.
      MATERIALS AND METHODS: Sixty male Wistar rats were used. They underwent midline
      laparotomy, for repair of a peritoneal injury, and were then assigned to four
      groups. Group 1 (Vitamin A) received 2000 units/kg intramuscular injection of
      vitamin A daily, post surgery, for two weeks; Group 2 (Vitamin C) received 100
      mg/kg oral vitamin C daily, after laparotomy, for two weeks; Group 3 (vitamins A
      and C) received 2000 units/kg intramuscular injection of vitamin A and 100 mg/kg
      oral vitamin C daily, after laparotomy, for two weeks, and Group four (Sham) rats
      did not receive any drugs. The adhesion, inflammation, fibrosis scores, and wound
      integrity were evaluated after two weeks. RESULTS: Rats in the vitamin C group
      had the lowest mean adhesion formation score (1 +/- 0.27) and the values of p
      were < 0.0001 for the vitamin A group and vitamin A and C groups and 0.003 for
      the sham group. Vitamin C also had the lowest fibrosis score (0.50 +/- 0.17)
      among the study groups and the values of p were < 0.0001 for the vitamin A group
      and vitamin A and C groups and 0.002 for the sham group. The mean inflammation
      score did not differ significantly among the study groups. The wound disruption
      strength was the highest in the vitamin C group and the difference was
      statistically significant in the sham group (1188.69 +/- 281.92 vs. 893.04 +/-
      187.46, p : 0.003). CONCLUSION: Administration of oral vitamin C reduces adhesion
      formation and improves wound healing.

PMID- 24672563
TI  - Epidemiology of venomous and semi-venomous snakebites (Ophidia: Viperidae,
      Colubridae) in the Kashan city of the Isfahan province in Central Iran.
AB  - BACKGROUND: Information on the epidemiology of venomous snake species responsible
      for envenomation to humans in Iran has not been well documented. In the Kashan
      city, venomous snakebite remains a recurring medical problem. Information
      providing the correct identification of snake species responsible for
      envenomation in this geographic region would be useful to regional medical
      clinics and personnel for the effective and optimal management of the patients.
      MATERIALS AND METHODS: In this cross-sectional study, all patient data was
      collected from Kashan city and its suburbs. The specific data relating to the
      taxonomic identification of snakes responsible for envenomation were evaluated. A
      general approach to the diagnosis and management of patients was also provided.
      Snakes responsible for bites were transported to a laboratory, where their
      taxonomic classification was confirmed based on key anatomical features and
      morphological characteristics. RESULTS: A total of 46 snakes were examined. Of
      these, 37 (80%) were non-venomous species, and 9 (20%) were identified as
      venomous. Seven of the nine venomous snake species (78%) were of the family
      Viperidae, and two specimens (22%) were in the family Colubridae. Specifically,
      the viperid species were Macrovipera lebetina obtusa, Pseudocerastes persicus,
      Pseudocerastes fieldi, and Echis carinatus. The two colubrid species were
      Malpolon monspessulanus insignitus and Psammophis schkari. CONCLUSION: Five
      different species of venomous snakes responsible for envenomation in the Kashan
      city region were confirmed. The viper, P. fieldi, was reported for the first time
      in the central part of Iran.

PMID- 24672564
TI  - Study of co-authorship network of papers in the Journal of Research in Medical
      Sciences using social network analysis.
AB  - BACKGROUND: Co-authorship is one of the most tangible forms of research
      collaboration. A co-authorship network is a social network in which the authors
      through participation in one or more publication through an indirect path have
      linked to each other. The present research using the social network analysis
      studied co-authorship network of 681 articles published in Journal of Research in
      Medical Sciences (JRMS) during 2008-2012. MATERIALS AND METHODS: The study was
      carried out with the scientometrics approach and using co-authorship network
      analysis of authors. The topology of the co-authorship network of 681 published
      articles in JRMS between 2008 and 2012 was analyzed using macro-level metrics
      indicators of network analysis such as density, clustering coefficient,
      components and mean distance. In addition, in order to evaluate the performance
      of each authors and countries in the network, the micro-level indicators such as
      degree centrality, closeness centrality and betweenness centrality as well as
      productivity index were used. The UCINET and NetDraw softwares were used to draw
      and analyze the co-authorship network of the papers. RESULTS: The assessment of
      the authors productivity in this journal showed that the first ranks were
      belonged to only five authors, respectively. Furthermore, analysis of the co
      authorship of the authors in the network demonstrated that in the betweenness
      centrality index, three authors of them had the good position in the network.
      They can be considered as the network leaders able to control the flow of
      information in the network compared with the other members based on the shortest
      paths. On the other hand, the key role of the network according to the
      productivity and centrality indexes was belonged to Iran, Malaysia and United
      States of America. CONCLUSION: Co-authorship network of JRMS has the
      characteristics of a small world network. In addition, the theory of 6 degrees 
      separation is valid in this network was also true.

PMID- 24672565
TI  - Manipulating measurement scales in medical statistical analysis and data mining:
      A review of methodologies.
AB  - BACKGROUND: selecting the correct statistical test and data mining method depends
      highly on the measurement scale of data, type of variables, and purpose of the
      analysis. Different measurement scales are studied in details and statistical
      comparison, modeling, and data mining methods are studied based upon using
      several medical examples. We have presented two ordinal-variables clustering
      examples, as more challenging variable in analysis, using Wisconsin Breast Cancer
      Data (WBCD). ORDINAL-TO-INTERVAL SCALE CONVERSION EXAMPLE: a breast cancer
      database of nine 10-level ordinal variables for 683 patients was analyzed by two
      ordinal-scale clustering methods. The performance of the clustering methods was
      assessed by comparison with the gold standard groups of malignant and benign
      cases that had been identified by clinical tests. RESULTS: the sensitivity and
      accuracy of the two clustering methods were 98% and 96%, respectively. Their
      specificity was comparable. CONCLUSION: by using appropriate clustering algorithm
      based on the measurement scale of the variables in the study, high performance is
      granted. Moreover, descriptive and inferential statistics in addition to modeling
      approach must be selected based on the scale of the variables.

PMID- 24672566
TI  - Utilization of open source electronic health record around the world: A
      systematic review.
AB  - Many projects on developing Electronic Health Record (EHR) systems have been
      carried out in many countries. The current study was conducted to review the
      published data on the utilization of open source EHR systems in different
      countries all over the world. Using free text and keyword search techniques, six
      bibliographic databases were searched for related articles. The identified papers
      were screened and reviewed during a string of stages for the irrelevancy and
      validity. The findings showed that open source EHRs have been wildly used by
      source limited regions in all continents, especially in Sub-Saharan Africa and
      South America. It would create opportunities to improve national healthcare level
      especially in developing countries with minimal financial resources. Open source
      technology is a solution to overcome the problems of high-costs and inflexibility
      associated with the proprietary health information systems. 

PMID- 24672567
TI  - The assessment of hepatitis B seroprevalence in persons with intravenous drug use
      history in the Isfahan province: Community-based study.
AB  - BACKGROUND: Hepatitis B with its complications has become one of the universal
      problems. Injection drug use is one of the most important risk factors in the
      transmission of hepatitis B. Therefore, we assessed hepatitis B virus prevalence
      among cases with a history of intravenous drug use (IVDU) as the first
      announcement-based study in this regard. MATERIALS AND METHODS: The announcement
      based detection of hepatitis B seroprevalence in volunteers with a history of
      intravenous drug use was conducted in the Isfahan province. A comprehensive
      community announcement was made in all the public places and to all physicians,
      in all the regions. One thousand five hundred and eighty-eight volunteers were
      invited to the Isfahan reference laboratories and serum samples were tested for
      HBs-Ag, HBc Ab, and HBs-Ab, using the enzyme-linked immunosorbent assay (ELISA)
      method. RESULTS: In this study, 1588 individuals volunteered, who were estimated
      to be 50% of all the expected intravenous drug users in the community. HBs Ag was
      detected in 4.2% of them. HBc Ab and HBs Ab were detected in order in 11.4 and
      17.3%, respectively. CONCLUSION: We estimated that the seroprevalence of
      hepatitis B positivity in intravenous drug users was moderate to high. Therefore,
      it was suggested that this group be encouraged to prevent acquiring infection by
      vaccination, education, counseling for risk reduction, and treatment of substance
      abuse, and finally hepatitis B virus (HBV) screening.

PMID- 24672568
TI  - A rare case of community-acquired native quadruple-valve endocarditis.
AB  - We report the case of a male patient with community-acquired quadruple-valve
      endocarditis on presumed normal native valves. This patient had originally
      presented elsewhere with generalized edema and malaise and had been diagnosed
      with suspicious endocarditis and renal dysfunction, for which he unfortunately
      received incomplete treatment. Transthoracic and transesophageal
      echocardiographic examinations confirmed quadruple-valve endocarditis and
      ventricular septal defect. 

PMID- 24672569
TI  - A successful treatment of rhinocerebral mucormycosis due to Rhizopus oryzae.
AB  - Mucormycosis is an invasive fungal infection caused by filamentous fungi of the
      Mucoraceae family. The genera most commonly responsible are Mucor or Rhizopus.
      The disease occurs mostly in association with diabetic ketoacidosis. Mucormycosis
      has an extremely high death rate even when aggressive surgery is done. Death
      rates range from 25-85% depending on the body area involved. A case of
      rhinocerebral mucormycosis in a 65-year-old diabetic male patient typically
      presenting as headache, especially in parietal and frontal lobes, with nose and
      left eye discharge. After clinical and laboratory examination, mucormycosis was
      diagnosed, and Rhizopus oryzae was isolated. Systemic therapy with amphotericin B
      administered intravenously then replaced by posaconazole by a combination of
      aggressive surgery. The patient was treated and followed up for one year. We
      emphasize the importance of early detection and aggressive treatment in the
      management of this fatal disease. 

PMID- 24672570
TI  - Combined choroidal neovascularization and hypopituitarism in a patient with
      homozygous mutation in methylenetetrahydrofolate reductase gene.
AB  - We report a case of choroidal neovascularization (CNV) secondary to
      methylenetetrahydrofolate reductase (MTHFR) gene mutation in a 20-year-old male
      patient with hypopituitarism. Treatment with three consecutive injections of
      intravitreal ranibizumab (anti-vascular endothelial growth factor) resulted in
      significant improvement of the patient's vision and the appearance of the macula.
      A search of the literature produced no previously reported case of MTHFR gene
      mutation associated both CNV and possibly hypopituitarism. With hormone
      replacement therapy of hypopituitarism, acetyl salicylic acid 100 mg/day also was
      started. The patient was clinically stable both for CNV and other thromboembolic
      disorders over a 6-month follow-up and also 1-year follow-up period. 

PMID- 24672571
TI  - Obesity predictors in people with chronic spinal cord injury: A common mistake.

PMID- 24672572
TI  - Resveratrol may improve osseointegration of dental implants in type 2 diabetes
      mellitus patients.

PMID- 24672573
TI  - Protective effects of herbal antioxidants on diabetic kidney disease.

PMID- 24672574
TI  - Infant mortality risk factors in a northeastern area of iran: A matched case-
      control study.

PMID- 24672575
TI  - Cervico-isthmic pregnancy is a potentially dangerous ectopic pregnancy.

PMID- 24672577
TI  - Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous
      Mistletoe Extracts (Viscum album L.) in Cancer Patients.
AB  - Background. In Europe, mistletoe extracts are widely used as a complementary
      cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive
      therapy in cancer patients within an anthroposophic medicine setting in Germany.
      Methods. A multicentre, observational study was performed within the Network
      Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by
      frequency, causality, severity, and seriousness. Potential risk factors, dose
      relationships and drug-drug interactions were investigated. Results. Of 1923
      cancer patients treated with subcutaneous mistletoe extracts, 283 patients
      (14.7%) reported 427 expected effects (local reactions <5 cm and increased body
      temperature <38 degrees C). ADRs were documented in 162 (8.4%) patients who
      reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or
      severe (4.2%). All were nonserious. Logistic regression analysis revealed that
      expected effects were more common in females, while immunoreactivity decreased
      with increasing age and tumour stage. No risk factors were identified for ADRs.
      ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred
      during mistletoe therapy received concurrent with conventional therapies.
      Conclusion. The results of this study indicate that mistletoe therapy is safe.
      ADRs were mostly mild to moderate in intensity and appear to be dose-related and
      explained by the immune-stimulating, pharmacological activity of mistletoe. 

PMID- 24672576
TI  - Wild Mushrooms in Nepal: Some Potential Candidates as Antioxidant and ACE
      Inhibition Sources.
AB  - Twenty-nine mushrooms collected in the mountainous areas of Nepal were analyzed
      for antioxidant activity by different methods, including Folin-Ciocalteu, ORAC,
      ABTS, and DPPH assays. Intracellular H2O2-scavenging activity was also performed
      on HaCaT cells. The results showed that phenolic compounds are the main
      antioxidant of the mushrooms. Among studied samples, Inonotus andersonii, and
      Phellinus gilvus exhibited very high antioxidant activity with the phenolic
      contents up to 310.8 and 258.7 mg GAE/g extracts, respectively. The H2O2
      scavenging assay on cells also revealed the potential of these mushrooms in the
      prevention of oxidative stress. In term of ACE-inhibition, results showed that
      Phlebia tremellosa would be a novel and promising candidate for antihypertensive
      studies. This mushroom exhibited even higher in vitro ACE-inhibition activity
      than Ganoderma lingzhi, with the IC50 values of the two mushrooms being 32  MU
      g/mL and 2  MU g/mL, respectively. This is the first time biological activities
      of mushrooms collected in Nepal were reported. Information from this study should
      be a valuable reference for future studies on antioxidant and ACE-inhibitory
      activities of mushrooms. 

PMID- 24672579
TI  - Segmentation of choroidal boundary in enhanced depth imaging OCTs using a
      multiresolution texture based modeling in graph cuts.
AB  - The introduction of enhanced depth imaging optical coherence tomography (EDI-OCT)
      has provided the advantage of in vivo cross-sectional imaging of the choroid,
      similar to the retina, with standard commercially available spectral domain (SD)
      OCT machines. A texture-based algorithm is introduced in this paper for fully
      automatic segmentation of choroidal images obtained from an EDI system of
      Heidelberg 3D OCT Spectralis. Dynamic programming is utilized to determine the
      location of the retinal pigment epithelium (RPE). Bruch's membrane (BM) (the
      blood-retina barrier which separates the RPE cells of the retina from the
      choroid) can be segmented by searching for the pixels with the biggest gradient
      value below the RPE. Furthermore, a novel method is proposed to segment the
      choroid-sclera interface (CSI), which employs the wavelet based features to
      construct a Gaussian mixture model (GMM). The model is then used in a graph cut
      for segmentation of the choroidal boundary. The proposed algorithm is tested on
      100 EDI OCTs and is compared with manual segmentation. The results showed an
      unsigned error of 2.48 +/- 0.32 pixels for BM extraction and 9.79 +/- 3.29 pixels
      for choroid detection. It implies significant improvement of the proposed method
      over other approaches like k-means and graph cut methods. 

PMID- 24672578
TI  - Monolayer spontaneous curvature of raft-forming membrane lipids.
AB  - Monolayer spontaneous curvatures for cholesterol, DOPE, POPE, DOPC, DPPC, DSPC,
      POPC, SOPC, and egg sphingomyelin were obtained using small-angle X-ray
      scattering (SAXS) on inverted hexagonal phases (HII). Spontaneous curvatures of
      bilayer forming lipids were estimated by adding controlled amounts to a HII
      forming template following previously established protocols. Spontaneous
      curvatures of both phosphatidylethanolamines and cholesterol were found to be at
      least a factor of two more negative than those of phosphatidylcholines, whose J0
      values are closer to zero. Interestingly, a significant positive J0 value was
      retrieved for DPPC. We further determined the temperature dependence of the
      spontaneous curvatures J0(T) in the range from 15 to 55  degrees C, resulting in
      a quite narrow distribution of -1 to -3 * 10-3 (nm  degrees C)-1 for most
      investigated lipids. The data allowed us to estimate the monolayer spontaneous
      curvatures of ternary lipid mixtures showing liquid ordered/liquid disordered
      phase coexistence. We report spontaneous curvature phase diagrams for
      DSPC/DOPC/Chol, DPPC/DOPC/Chol and SM/POPC/Chol and discuss effects on protein
      insertion and line tension.

PMID- 24672581
TI  - OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG
      INJURY FROM HYPEROXIA AND SEPSIS.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of many
      acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults
      and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection
      and oxygen toxicity, which result in pulmonary vascular endothelial injury,
      contribute to impaired vascular growth and alveolar simplification seen in the
      lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell
      proliferation, causes DNA damage and promotes cell death by causing mitochondrial
      dysfunction. The objective of this study was to use an optical imaging technique
      to evaluate the variations in fluorescence intensities of the auto-fluorescent
      mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats.
      The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox
      ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries.
      Here, we investigated whether the changes in metabolic state can be used as a
      marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide
      (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of
      lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2)
      pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and
      hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the
      respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as
      compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no
      significant effect on lung tissue NADH RR as compared to that for normoxic or
      hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of
      oxidative stress level in lung injury caused by two clinically important
      conditions: hyperoxia and LPS exposure.

PMID- 24672580
TI  - Accelerated atherosclerosis in SLE: mechanisms and prevention approaches.
AB  - Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease
      characterized by increased serum autoantibody levels and tissue damage. With
      improved diagnosis and more effective treatment of the resultant kidney disease,
      accelerated atherosclerosis has become a major cause of morbidity in patients
      suffering from SLE. Although the exact mechanisms for SLE-accelerated
      atherosclerosis are unknown, multiple factors have been established as potential
      players in this process. Among these potential players are dysregulation of T and
      B cell populations and increased circulating levels of inflammatory cytokines. In
      addition, SLE patients exhibit a proatherogenic lipid profile characterized by
      low HDL and high LDL and triglycerides. Recent therapeutic approaches have
      focused on targeting B cells, the producers of autoantibodies, but most studies
      do not consider the effects of these treatments on atherosclerosis. Evidence
      suggests that T cells play a major role in SLE-accelerated atherosclerosis.
      Therefore, therapies targeted at T cells may also prove invaluable in treating
      SLE and atherosclerosis.

PMID- 24672582
TI  - Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles
      for delivery of siRNA cancer therapeutics.
AB  - Effective delivery holds the key to successful in vivo application of therapeutic
      small interfering RNA (siRNA). In this work, we have developed a universal siRNA
      carrier consisting of a mesoporous silica nanoparticle (MSNP) functionalized with
      cyclodextrin-grafted polyethylenimine (CP). CP provides positive charge for
      loading of siRNA through electrostatic interaction and enables effective
      endosomal escape of siRNA. Using intravital microscopy we were able to monitor
      tumor enrichment of CP-MSNP/siRNA particles in live mice bearing orthotopic MDA
      MB-231 xenograft tumors. CP-MSNP delivery of siRNA targeting the M2 isoform of
      the glycolytic enzyme pyruvate kinase (PKM2) resulted in effective knockdown of
      gene expression in vitro and in vivo. Suppression of PKM2 led to inhibition of
      tumor cell growth, invasion, and migration. 

PMID- 24672584
TI  - Theranostic Au cubic nano-aggregates as potential photoacoustic contrast and
      photothermal therapeutic agents.
AB  - Multifunctional nanostructures combining diagnosis and therapy modalities into
      one entity have drawn much attention in the biomedical applications. Herein, we
      report a simple and cost-effective method to synthesize a novel cubic Au nano
      aggregates structure with edge-length of 80 nm (Au-80 CNAs), which display strong
      near-infrared (NIR) absorption, excellent water-solubility, good photothermal
      stability, and high biocompatibility. Under 808 nm laser irradiation for 5 min,
      the temperature of the solution containing Au-80 CNAs (100 MUg/mL) increased by
      ~38  degrees C. The in vitro and in vivo studies demonstrated that Au-80 CNAs
      could act as both photothermal therapeutic (PTT) agents and photoacoustic imaging
      (PAI) contrast agents, indicating that the only one nano-entity of Au-80 CNAs
      shows great potentials for theranostic applications. Moreover, this facile and
      cost-effective synthetic method provides a new strategy to prepare stable Au
      nanomaterials with excellent optical properties for biomedical applications. 

PMID- 24672583
TI  - Bioabsorbable stent quo vadis: a case for nano-theranostics.
AB  - Percutaneous coronary intervention (PCI) is one of the most commonly performed
      invasive medical procedures in medicine today. Since the first coronary balloon
      angioplasty in 1977, interventional cardiology has seen a wide array of
      developments in PCI. Bare metal stents (BMS) were soon superseded by the
      revolutionary drug-eluting stents (DES), which aimed to address the issue of
      restenosis found with BMS. However, evidence began to mount against DES, with
      late-stent thrombosis (ST) rates being higher than that of BMS. The bioabsorbable
      stent may be a promising alternative, providing vessel patency and support for
      the necessary time required and thereafter degrade into safe non-toxic compounds
      which are reabsorbed by the body. This temporary presence provides no triggers
      for ST, which is brought about by non-endothelialized stent struts and drug
      polymers remaining in vivo for extended periods of time. Likewise, nano
      theranostics incorporated into a bioabsorbable stent of the future may provide an
      incredibly valuable single platform offering both therapeutic and diagnostic
      capabilities. Such a stent may allow delivery of therapeutic particles to
      specific sites thus keeping potential toxicity to a minimum, improved ease of
      tracking delivery in vivo by embedding imaging agents, controlled rate of therapy
      release and protection of the implanted therapy. Indeed, nanocarriers may allow
      an increased therapeutic index as well as offer novel post-stent implantation
      imaging and diagnostic methods for atherosclerosis, restenosis and thrombosis. It
      is envisioned that a nano-theranostic stent may well form the cornerstone of
      future stent designs in clinical practice. 

PMID- 24672586
TI  - Sorafenib-induced acute interstitial pneumonia in patients with advanced
      hepatocellular carcinoma: report of three cases.
AB  - Little is known about acute interstitial pneumonia (AIP) induced by sorafenib
      therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we
      present three patients with advanced HCC who developed AIP during sorafenib
      therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who
      developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was
      discontinued immediately, and prednisolone was started. His pneumonia resolved. A
      drug-induced lymphocyte stimulation test for sorafenib was positive. Case 2 was a
      75-year-old man and case 3 was a 77-year-old man, both of whom developed high
      grade fever and hypoxemia during sorafenib therapy, and were diagnosed with AIP.
      In spite of high-dose steroid therapy, their respiratory failure worsened and
      both patients died. In all three cases, serum KL-6 or surfactant protein D
      concentrations were elevated, and blood and sputum cultures did not grow
      pathogens. All three patients were smokers with restrictive lung disease on
      preoperative respiratory function testing, but did not have respiratory symptoms
      before sorafenib therapy. The clinical features of these three cases suggest that
      male gender, older age, smoking history, and lung disease are associated with
      acute sorafenib-induced AIP in patients with advanced HCC. 

PMID- 24672585
TI  - Longitudinal PET imaging of muscular inflammation using 18F-DPA-714 and 18F
      Alfatide II and differentiation with tumors.
AB  - AIM: (18)F-DPA-714 is a PET tracer that recognizes macrophage translocator
      protein (TSPO), and (18)F-Alfatide II ((18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) is
      specific for integrin alphavbeta3. This study aims to apply these two tracers for
      longitudinal PET imaging of muscular inflammation, and evaluate the value of
      (18)F-DPA-714 in differentiating inflammation from tumor. METHODS: RAW264.7 mouse
      macrophage cells were used for cell uptake analysis of (18)F-DPA-714. A mouse
      hind limb muscular inflammation model was established by intramuscular injection
      of turpentine oil. For the inflammation model, PET imaging was performed at
      different days using (18)F-DPA-714 and (18)F-Alfatide II. The specificity of the
      imaging probes was tested by co- or pre-injection of PK11195 or unlabeled RGD
      (Arg-Gly-Asp) peptide. PET imaging using (18)F-DPA-714 was performed in A549,
      HT29, U87MG, INS-1, and 4T1 xenograft models. Immunofluorescence staining was
      performed to evaluate infiltrated macrophages and angiogenesis in inflammation
      and/or tumors. RESULTS: Uptake of (18)F-DPA-714 in RAW264.7 cells was 45.5% at 1
      h after incubation, and could be blocked by PK11195. PET imaging showed increased
      (18)F-DPA-714 and (18)F-Alfatide II uptake at inflammatory muscles. Peak uptake
      of (18)F-DPA-714 was seen on day 6 (4.02 +/- 0.64 %ID/g), and peak uptake of
      (18)F-Alfatide II was shown on day 12 (1.87 +/- 0.35 %ID/g) at 1 h p.i.. Tracer
      uptakes could be inhibited by PK11195 for (18)F-DPA-714 or cold RGD for (18)F
      Alfatide II. Moreover, macrophage depletion with liposomal clodronate also
      reduced the local accumulation of both tracers. A549, HT29, U87MG, INS-1, and 4T1
      tumor uptakes of (18)F-DPA-714 (0.46 +/- 0.28, 0.91 +/- 0.08, 1.69 +/- 0.67, 1.13
      +/- 0.33, 1.22 +/- 0.55 %ID/g at 1 h p.i., respectively) were significantly lower
      than inflammation uptake (All P < 0.05). CONCLUSION: PET imaging using (18)F-DPA
      714 as a TSPO targeting tracer could evaluate the dynamics of macrophage
      activation and infiltration in different stages of inflammatory diseases. The
      concomitant longitudinal PET imaging with both (18)F-DPA-714 and (18)F-Alfatide
      II matched the causal relationship between macrophage infiltration and
      angiogenesis. Moreover, we found (18)F-DPA-714 uptake in several types of tumors
      is significantly lower than that in inflammatory muscles, suggesting (18)F-DPA
      714 PET has the potential for better differentiation of tumor and non-tumor
      inflammation.

PMID- 24672587
TI  - Optimization of a Low Magnesium, Cholesterol-Containing Diet for the Development
      of Atherosclerosis in Rabbits.
AB  - The cholesterol-fed rabbit is useful for atherosclerosis research. We describe
      development of a low-magnesium (Mg) cholesterol-containing diet to accelerate
      atherosclerosis in this model. Male New Zealand White rabbits were fed either
      chow or one of four atherogenic diets: 1% cholesterol 10% fat 0.11% Mg, 1%
      cholesterol 10% fat 0.40% Mg, 2% cholesterol 20% fat 0.11% Mg, or 2% cholesterol
      20% fat 0.40% Mg. While feed intake decreased in cholesterol-fed rabbits, they
      were able to maintain their body weights. Rabbits consuming cholesterol
      experienced profound hypercholesterolemia and tissue lipid accumulation, with
      plasma cholesterol levels above 1500 mg/dl for all groups at the completion of
      the study. Liver and spleen lipid content and liver cholesterol content also
      increased. Aortic arch atheroma thickness was greatest in 1% cholesterol 10% fat
      0.11% Mg animals. Tissue Mg levels decreased in cholesterol-fed animals compared
      to chow-fed controls, despite equal or greater serum Mg levels. Our results
      indicate that the 1% cholesterol 10% fat 0.11% Mg diet was optimal at promoting
      hypercholesterolemia and atherosclerosis while minimizing health complications
      for the animals. The low Mg cholesterol diet will be useful to other biomedical
      researchers interested in utilizing the rabbit for cardiovascular disease
      research.

PMID- 24672588
TI  - Suicide Risk Assessment Training for Psychology Doctoral Programs: Core
      Competencies and a Framework for Training.
AB  - Clinical and counseling psychology programs currently lack adequate evidence
      based competency goals and training in suicide risk assessment. To begin to
      address this problem, this article proposes core competencies and an integrated
      training framework that can form the basis for training and research in this
      area. First, we evaluate the extent to which current training is effective in
      preparing trainees for suicide risk assessment. Within this discussion, sample
      and methodological issues are reviewed. Second, as an extension of these
      methodological training issues, we integrate empirically- and expert-derived
      suicide risk assessment competencies from several sources with the goal of
      streamlining core competencies for training purposes. Finally, a framework for
      suicide risk assessment training is outlined. The approach employs Objective
      Structured Clinical Examination (OSCE) methodology, an approach commonly utilized
      in medical competency training. The training modality also proposes the Suicide
      Competency Assessment Form (SCAF), a training tool evaluating self- and observer
      ratings of trainee core competencies. The training framework and SCAF are ripe
      for empirical evaluation and potential training implementation.

PMID- 24672589
TI  - Delayed functional recovery in presymptomatic mSOD1G93A mice following facial
      nerve crush axotomy.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      involving progressive loss of motoneurons (MN). Axonal pathology and presynaptic
      deaf-ferentation precede MN degeneration during disease progression in patients
      and the ALS mouse model (mSOD1). Previously, we determined that a functional
      adaptive immune response is required for complete functional recovery following a
      facial nerve crush axotomy in wild-type (WT) mice. In this study, we investigated
      the effects of facial nerve crush axotomy on functional recovery and facial MN
      survival in presymptomatic mSOD1 mice, relative to WT mice. The results indicate
      that functional recovery and facial MN survival levels are significantly reduced
      in presymptomatic mSOD1, relative to WT, and similar to what has previously been
      observed in immunodeficient mice. It is concluded that a potential immune system
      defect exists in the mSOD1 mouse that negatively impacts neuronal survival and
      regeneration following target disconnection associated with peripheral nerve
      axotomy.

PMID- 24672591
TI  - Splenic laceration and pulmonary contusion injury from bean bag weapon.

PMID- 24672592
TI  - High-pressure injection injury with molten aluminum.

PMID- 24672590
TI  - Race/Ethnicity, Obesity, and Related Cardio-Metabolic Risk Factors: A Life-Course
      Perspective.
AB  - The adoption of health behaviors characterized by minimal energy expenditure and
      overconsumption of energy has led to cardiometabolic risk factors in pregnancy,
      childhood, and youth, all of which increase the prevalence of cardiovascular
      disease in adulthood. The propensity to develop abdominal obesity and
      cardiometabolic risk factors appears to disproportionally affect non-white ethnic
      groups. While the majority of observational research has been conducted in
      populations of European origin, studies in non-white ethnic groups across the
      life-course are underway and there is evidence that unique ethnic-specific
      differences exist. This review will focus on the life-course determinants of
      obesity and its related cardio-metabolic risk factors among diverse ethnic groups
      including people of Afro-Caribbean origin, South Asian, East Asian, and
      indigenous ancestry.

PMID- 24672593
TI  - Diagnosis of Fournier's Gangrene on bedside ultrasound.

PMID- 24672594
TI  - Cardiac sarcoma: unusual cause of intracardiac contrast filling defect.
AB  - A 28-year-old female was transferred to the emergency department from her
      physician's office for further evaluation of tachycardia. She was being seen for
      a recent illness which included nausea, vomiting, diarrhea and fevers. The
      patient endorsed fatigue, dyspnea on exertion, and extremity edema. She had no
      chest pain or cough. Exam revealed a pale, fatigued, mildly ill-appearing female
      with bilateral lower extremity edema and diminished breath sounds on the right.
      Chest radiograph revealed a large right pleural effusion (Figure 1). Computed
      tomographic angiography of the chest was performed (Figure 2). 

PMID- 24672595
TI  - Lemierre's Syndrome.

PMID- 24672596
TI  - Phenytoin toxicity from cocaine adulteration.
AB  - The use of phenytoin (PHT) as a cocaine adulterant was reported decades ago; that
      practice is still current. Ironically PHT has also been used for the treatment of
      cocaine dependence. A drug smuggler developed PHT toxicity after swallowing
      several rocks of crack. We investigated the current trends of PHT as a cocaine
      adulterant and its toxicological implications. We also reviewed the clinical use
      of PTH in relation to cocaine. The use of PHT as cocaine cut is a current
      practice. This may affect the clinical manifestations and the management of the
      cocaine-related visits to the emergency department. 

PMID- 24672597
TI  - The ethics of the missing straw.
AB  - This case report details the emergency department course of a 34 year-old female
      who presented with abdominal pain and vaginal bleeding after reportedly falling
      one week earlier. She was subsequently found to have a drinking straw within her
      uterus next to an eight week-old live intrauterine pregnancy on ultrasound. This
      case report and discussion reviews the literature on retained foreign bodies in
      pregnancy while addressing the added complications of an evasive patient and a
      difficult consultant with significant intra-specialty disagreement. 

PMID- 24672598
TI  - Delayed presentation of deep sternal wound infection.
AB  - Deep sternal wound infections (DSWI) are infections of the sternum, mediastinum,
      or the muscle, fascia and soft tissue that overlie the sternum, typically
      occurring within a month of cardiac surgery. They are infrequent though severe
      complications of cardiac surgery. Diagnosis is made by the clinical presentation
      of fever, chest pain, or sternal instability in the setting of wound drainage,
      positive wound cultures, or chest radiographic findings. We describe the case of
      an elderly man presenting 6 months after cardiac surgery with DSWI. Due to the
      atypical nature of such a late presentation, definitive therapy was delayed.
      Given a severely ill patient with multiple risk factors for poor wound healing,
      the clinician must maintain a high index of suspicion for DSWI despite a delayed
      presentation. 

PMID- 24672599
TI  - Emergency department crowding and loss of medical licensure: a new risk of
      patient care in hallways.
AB  - We report the case of a 32-year-old male recently diagnosed with type 2 diabetes
      treated at an urban university emergency department (ED) crowded to 250% over
      capacity. His initial symptoms of shortness of breath and feeling ill for several
      days were evaluated with chest radiograph, electrocardiogram (EKG), and
      laboratory studies, which suggested mild diabetic ketoacidosis. His medical care
      in the ED was conducted in a crowded hallway. After correction of his metabolic
      abnormalities he felt improved and was discharged with arrangements made for
      outpatient follow-up. Two days later he returned in cardiac arrest, and
      resuscitation efforts failed. The autopsy was significant for multiple acute and
      chronic pulmonary emboli but no coronary artery disease. The hospital settled the
      case for $1 million and allocated major responsibility to the treating emergency
      physician (EP). As a result the state medical board named the EP in a
      disciplinary action, claiming negligence because the EKG had not been personally
      interpreted by that physician. A formal hearing was conducted with the EP's
      medical license placed in jeopardy. This case illustrates the risk to EPs who
      treat patients in crowded hallways, where it is difficult to provide the highest
      level of care. This case also demonstrates the failure of hospital administration
      to accept responsibility and provide resources to the ED to ensure patient
      safety. 

PMID- 24672600
TI  - Incarcerated diaphragmatic hernia with bowel perforation presenting as a tension
      pneumothorax.
AB  - We present an interesting case of a patient with a previously known diaphragmatic
      hernia in which the colon became incarcerated, ischemic and finally perforated.
      She had no prior history of abdominal pain or vomiting, yet she presented with
      cardiovascular collapse. She was quickly diagnosed with a tension pneumothorax
      and treated accordingly. To our knowledge, this is the only case report of a
      tension pneumothorax associated with perforated bowel that was not in the setting
      of trauma or colonoscopy. 

PMID- 24672601
TI  - Popliteal artery injury associated with blunt trauma to the knee without fracture
      or dislocation.
AB  - Popliteal artery injuries are frequently seen with fractures, dislocations, or
      penetrating injuries. Concern about arterial injury and early recognition of the
      possibility of arterial injury is crucial for the salvage of the extremity. This
      article provides an outline of the diagnostic challenges related to these rare
      vascular injuries and emphasizes the necessity for a high level of suspicion,
      even in the absence of a significant penetrating injury, knee dislocation,
      fracture, or high-velocity trauma mechanism. The importance of a detailed
      vascular examination of a blunt trauma patient is emphasized. 

PMID- 24672602
TI  - Complete ventricular asystole in a patient with altered mental status.
AB  - Patients who present with recurrent syncope are at risk for having underlying
      conduction disease, which may worsen if not promptly recognized and treated. We
      describe a patient who initially presented to a Mexican clinic with recurrent
      syncope and an electrocardiogram that showed complete heart block. After being
      transferred to our emergency department, he deteriorated into complete
      ventricular asystole with preserved atrial function and required placement of a
      transvenous cardiac pacemaker. 

PMID- 24672603
TI  - Urinary metabolomic analysis to detect changes after intravenous, non-ionic, low
      osmolar iodinated radiocontrast for computerized tomographic imaging.
AB  - INTRODUCTION: Contrast-induced nephropathy is a result of injury to the proximal
      tubules caused by oxidative stress and ischemia. Metabolomics is a novel
      technique that has been used to identify renal damage from drug toxicities. The
      objective of this study is to analyze the metabolic changes in the urine after
      dosing with intravenous (IV) contrast for computed tomograph (CT) of the chest.
      METHODS: A convenience sample of patients undergoing a chest ct with iv contrast
      who had at least one of the following: age >=50 years, diabetes, heart failure,
      chronic kidney disease, coronary artery disease, or diastolic blood pressure >90
      mmHg -- were eligible for enrollment. Urine samples were collected prior to
      imaging and 4-6 hours post imaging. Samples underwent gas chromography/mass
      spectrometry profiling. We measured peak metabolite values and log transformed
      data. Paired T tests were calculated. We used significance analysis of
      microarrays (SAM) to determine the most significant metabolites. RESULTS: The
      cohort comprised 14 patients with matched samples; 9/14 (64.3) were males, and
      the median age was 61 years (IQR 50-68). A total of 158 metabolites were
      identified. Using SAM we identified 9 metabolites that were identified as
      significant using a delta of 1.6. CONCLUSION: Changes in urinary metabolites are
      present soon after contrast administration. This change in urinary metabolites
      may be potential early identifiers of contrast-induced nephropathy and could
      identify patients at high-risk for developing this condition.

PMID- 24672604
TI  - Hospital factors impact variation in emergency department length of stay more
      than physician factors.
AB  - INTRODUCTION: To analyze the correlation between the many different emergency
      department (ED) treatment metric intervals and determine if the metrics directly
      impacted by the physician correlate to the "door to room" interval in an ED
      (interval determined by ED bed availability). Our null hypothesis was that the
      cause of the variation in delay to receiving a room was multifactorial and does
      not correlate to any one metric interval. METHODS: We collected daily interval
      averages from the ED information system, Meditech(c). Patient flow metrics were
      collected on a 24-hour basis. We analyzed the relationship between the time
      intervals that make up an ED visit and the "arrival to room" interval using
      simple correlation (Pearson Correlation coefficients). Summary statistics of
      industry standard metrics were also done by dividing the intervals into 2 groups,
      based on the average ED length of stay (LOS) from the National Hospital
      Ambulatory Medical Care Survey: 2008 Emergency Department Summary. RESULTS:
      Simple correlation analysis showed that the doctor-to-discharge time interval had
      no correlation to the interval of "door to room (waiting room time)", correlation
      coefficient (CC) (CC=0.000, p=0.96). "Room to doctor" had a low correlation to
      "door to room" CC=0.143, while "decision to admitted patients departing the ED
      time" had a moderate correlation of 0.29 (p <0.001). "New arrivals" (daily
      patient census) had a strong correlation to longer "door to room" times, 0.657,
      p<0.001. The "door to discharge" times had a very strong correlation CC=0.804
      (p<0.001), to the extended "door to room" time. CONCLUSION: Physician-dependent
      intervals had minimal correlation to the variation in arrival to room time. The
      "door to room" interval was a significant component to the variation in "door to
      discharge" i.e. LOS. The hospital-influenced "admit decision to hospital bed"
      i.e. hospital inpatient capacity, interval had a correlation to delayed "door to
      room" time. The other major factor affecting department bed availability was the
      "total patients per day." The correlation to the increasing "door to room" time
      also reflects the effect of availability of ED resources (beds) on the patient
      evaluation time. The time that it took for a patient to receive a room appeared
      more dependent on the system resources, for example, beds in the ED, as well as
      in the hospital, than on the physician.

PMID- 24672605
TI  - Impact of a teaching service on emergency department throughput.
AB  - INTRODUCTION: There are 161 emergency medicine residency programs in the United
      States, many of which have medical students rotating through the emergency
      department (ED). Medical students are typically supervised by senior residents or
      attendings while working a regular shift. Many believe that having students see
      and present patients prolongs length of stay (LOS), as care can be delayed. Our
      institution implemented a unique method of educating medical students while in
      the ED with the creation of a teaching service, whose primary goal is education
      in the setting of clinical care. The objective of this study was to explore the
      effect of the teaching service on efficiency by describing LOS and number of
      patients seen on shifts with and without a teaching service. METHODS: This was a
      retrospective chart review performed over a 12-month period of visits to an urban
      academic ED. We collected data on all patients placed in a room between 14:00 and
      19:59, as these were the hours that the teaching shift worked in the department.
      We categorized shifts as 1) a teaching service with students (TWS); 2) a teaching
      service without students (TWOS); and 3) no teaching service (NTS). LOS and median
      number of patients seen on days with a teaching service, both with and without
      students (TWS and TWOS), was compared to LOS on days without a teaching service
      (NTS). RESULTS: The median LOS on shifts with a dedicated teaching service
      without students (TWOS) was 206 minutes, while the median LOS on shifts with a
      teaching service with students (TWS) was 220 minutes. In comparison, the median
      LOS on shifts when no teaching service was present (NTS) was 202.5 minutes. The
      median number of patients seen on shifts with the teaching service with students
      (TWS) was 44, identical to the number seen on shifts when the teaching service
      was present without students (TWOS). When the teaching service was absent (NTS),
      the median number of patients seen was 40. CONCLUSION: A teaching service in the
      ED is a novel educational model for medical student and resident instruction that
      increases total ED patient throughput and has only a modest effect on increased
      median length of stay for patients.

PMID- 24672606
TI  - Emergency department length of stay: accuracy of patient estimates.
AB  - INTRODUCTION: Managing a patient's expectations in the emergency department (ED)
      environment is challenging. Previous studies have identified several factors
      associated with ED patient satisfaction. Lengthy wait times have shown to be
      associated with dissatisfaction with ED care. Understanding that patients are
      inaccurate at their estimation of wait time, which could lead to lower
      satisfaction, provides administrators possible points of intervention to help
      improve accuracy of estimation and possibly satisfaction with the ED. This study
      was undertaken to examine the accuracy of patient estimates of time periods in an
      ED and identify factors associated with accuracy. METHOD: In this prospective
      convenience sample survey at UTMC ED, we collected data between March and July
      2012. Outcome measures included duration of each phase of ED care and patient
      estimates of these time periods. RESULTS: Among 309 participants, the majority
      underestimated the total length of stay (LOS) in the ED (median difference -7
      minutes (IQR -29-12)). There was significant variability in ED LOS (median 155
      minutes (IQR 75-240)). No significant associations were identified between
      accuracy of time estimates and gender, age, race, or insurance status.
      Participants with longer ED LOS demonstrated lower patient satisfaction scores
      (p<0.001). CONCLUSION: Patients demonstrated inaccurate time estimates of ED
      treatment times, including total LOS. Patients with longer ED LOS had lower
      patient satisfaction scores.

PMID- 24672607
TI  - Impact of decontamination therapy on ultrasound visualization of ingested pills.
AB  - INTRODUCTION: Acute toxic ingestion is a common cause of morbidity and mortality.
      Emergency physicians (EP) caring for overdose (OD) patients are often required to
      make critical decisions with incomplete information. Point of care ultrasound
      (POCUS) may have a role in assisting EPs manage OD patients. We evaluated the
      impact of different liquid adjuncts used for gastric decontamination on
      examiners' ability to identify the presence of tablets using POCUS, and assessed
      examiners' ability to quantify the numbers of tablets in a simulated massive OD.
      METHODS: This prospective, blinded, pilot study was performed at an academic
      emergency department. Study participants were volunteer resident and staff EPs
      trained in POCUS. Five nontransparent, sealed bags were prepared with the
      following contents: 1 liter (L) of water, 1 L of water with 50 regular aspirin
      (ASA) tablets, 1 L of water with 50 enteric-coated aspirin tablets (ECA), 1 L of
      polyethylene glycol (PEG) with 50 ECA, and 1 L of activated charcoal (AC) with 50
      ECA. After performing POCUS on each of the bags using a 10-5 MHz linear array
      transducer, participants completed a standardized questionnaire composed of the
      following questions: (1) Were pills present? YES/NO; (2) If tablets were
      identified, estimate the number (1-10, 11-25, >25). We used a single test on
      proportions using the binomial distribution to determine if the number of EPs who
      identified tablets differed from 50% chance. For those tablets identified in the
      different solutions, another test on proportions was used to determine whether
      the type of solution made a difference. Since 3 options were available, we used a
      probability of 33.3%. RESULTS: Thirty-seven EPs completed the study. All (37/37)
      EP's correctly identified the absence of tablets in the bag containing only
      water, and the presence of ECA in the bags containing water and PEG. For Part 2
      of the study, most participants - 25/37 (67.5%) using water, 23/37 (62.1%) using
      PEG, and all 37 (100%) using AC - underestimated the number of ECA pills in
      solution by at least 50%. CONCLUSION: There may be a potential role for POCUS in
      the evaluation of patients suspected of acute, massive ingested OD. EPs
      accurately identified the presence of ECA in water and PEG, but underestimated
      the number of tablets in all tested solutions.

PMID- 24672608
TI  - Impact of an abbreviated cardiac enzyme protocol to aid rapid discharge of
      patients with cocaine-associated chest pain in the clinical decision unit.
AB  - INTRODUCTION: In 2007 there were 64,000 visits to the emergency department (ED)
      for possible myocardial infarction (MI) related to cocaine use. Prior studies
      have demonstrated that low- to intermediate-risk patients with cocaine-associated
      chest pain can be safely discharged after 9-12 hours of observation. The goal of
      this study was to determine the safety of an 8-hour protocol for ruling out MI in
      patients who presented with cocaine-associated chest pain. METHODS: We conducted
      a retrospective review of patients treated with an 8-hour cocaine chest pain
      protocol between May 1, 2011 and November 30, 2012 who were sent to the clinical
      decision unit (CDU) for observation. The protocol included serial cardiac
      biomarker testing with Troponin-T, CK-MB (including delta CK-MB), and total CK at
      0, 2, 4, and 8 hours after presentation with cardiac monitoring for the
      observation period. Patients were followed up for adverse cardiac events or death
      within 30 days of discharge. RESULTS: There were 111 admissions to the CDU for
      cocaine chest pain during the study period. One patient had a delta CK-MB of 1.6
      ng/ml, but had negative Troponin-T at all time points. No patient had a positive
      Troponin-T or CK-MB at 0, 2, 4 or 8 hours, and there were no MIs or deaths within
      30 days of discharge. Most patients were discharged home (103) and there were 8
      inpatient admissions from the CDU. Of the admitted patients, 2 had additional
      stress tests that were negative, 1 had additional cardiac biomarkers that were
      negative, and all 8 patients were discharged home. The estimated risk of missing
      MI using our protocol is, with 99% confidence, less than 5.1% and with 95%
      confidence, less than 3.6% (99% CI, 0-5.1%; 95% CI, 0-3.6%). CONCLUSION:
      Application of an abbreviated cardiac enzyme protocol resulted in the safe and
      rapid discharge of patients presenting to the ED with cocaine-associated chest
      pain.

PMID- 24672609
TI  - Factors important to applicants to osteopathic versus allopathic emergency
      medicine residency programs.
AB  - INTRODUCTION: Our objective is to evaluate the factors important to osteopathic
      applicants when selecting an American College of Osteopathic Emergency Physicians
      accredited emergency medicine (EM) residency and to compare these results with
      previous allopathic EM studies. METHODS: We gave osteopathic applicants a survey
      during interview season to be filled out anonymously at the end of their
      interview day. This survey included 18 factors which the applicants were asked to
      rank between 1 ("not very important") to 4 ("very important"). We then compared
      results to prior results of the same survey. RESULTS: Forty applicants (67%) out
      of 60 completed the survey. From these individuals, we noticed differences in the
      top factors listed by the applicants when compared to allopathic interviewees,
      the most notable being the unimportance of geographic location of the program to
      osteopathic applicants as manifested by osteopathic student average score of 2.8
      (standard deviation 0.75) verses allopathic student average of 3.6 (standard
      deviation 0.06). CONCLUSION: Of the top 5 factors listed by the applicants, only
      1 (AOA-approved residency) is an objective factor that the program has a role in
      controlling. The remainder are mainly subjective factors based on applicant's
      perceptions of the program.

PMID- 24672610
TI  - 4,871 Emergency airway encounters by air medical providers: a report of the air
      transport emergency airway management (NEAR VI: "A-TEAM") project.
AB  - INTRODUCTION: Pre-hospital airway management is a key component of resuscitation
      although the benefit of pre-hospital intubation has been widely debated. We
      report a large series of pre-hospital emergency airway encounters performed by
      air-transport providers in a large, multi-state system. METHODS: We
      retrospectively reviewed electronic intubation flight records from an 89
      rotorcraft air medical system from January 01, 2007, through December 31, 2009.
      We report patient characteristics, intubation methods, success rates, and rescue
      techniques with descriptive statistics. We report proportions with 95% confidence
      intervals and binary comparisons using chi square test with p-values <0.05
      considered significant. RESULTS: 4,871 patients had active airway management,
      including 2,186 (44.9%) medical and 2,685 (55.1%) trauma cases. There were 4,390
      (90.1%) adult and 256 (5.3%) pediatric (age <= 14) intubations; 225 (4.6%) did
      not have an age recorded. 4,703 (96.6%) had at least one intubation attempt.
      Intubation was successful on first attempt in 3,710 (78.9%) and was ultimately
      successful in 4,313 (91.7%). Intubation success was higher for medical than
      trauma patients (93.4% versus 90.3%, p=0.0001 JT test). 168 encounters were
      managed primarily with an extraglottic device (EGD). Cricothyrotomy was performed
      35 times (0.7%) and was successful in 33. Patients were successfully oxygenated
      and ventilated with an endotracheal tube, EGD, or surgical airway in 4809 (98.7%)
      encounters. There were no reported deaths from a failed airway. CONCLUSION:
      Airway management, predominantly using rapid sequence intubation protocols, is
      successful within this high-volume, multi-state air-transport system.

PMID- 24672611
TI  - Ambulatory cardiac monitoring for discharged emergency department patients with
      possible cardiac arrhythmias.
AB  - INTRODUCTION: Many emergency department (ED) patients have symptoms that may be
      attributed to arrhythmias, necessitating outpatient ambulatory cardiac
      monitoring. Consensus is lacking on the optimal duration of monitoring. We
      describe the use of a novel device applied at ED discharge that provides
      continuous prolonged cardiac monitoring. METHODS: We enrolled discharged adult ED
      patients with symptoms of possible cardiac arrhythmia. A novel, single use
      continuous recording patch (Zio(r)Patch) was applied at ED discharge. Patients
      wore the device for up to 14 days or until they had symptoms to trigger an event.
      They then returned the device by mail for interpretation. Significant arrhythmias
      are defined as: ventricular tachycardia (VT) >=4 beats, supraventricular
      tachycardia (SVT) >=4 beats, atrial fibrillation, >=3 second pause, 2nd degree
      Mobitz II, 3rd degree AV Block, or symptomatic bradycardia. RESULTS: There were
      174 patients were enrolled and all mailed back their devices. The average age was
      52.2 (+/- 21.0) years, and 55% were female. The most common indications for
      device placement were palpitations 44.8%, syncope 24.1% and dizziness 6.3%.
      Eighty-three patients (47.7%) had >=1 arrhythmias and 17 (9.8%) were symptomatic
      at the time of their arrhythmia. Median time to first arrhythmia was 1.0 days
      (IQR 0.2-2.8) and median time to first symptomatic arrhythmia was 1.5 days (IQR
      0.4-6.7). 93 (53.4%) of symptomatic patients did not have any arrhythmia during
      their triggered events. The overall diagnostic yield was 63.2% CONCLUSION: The
      Zio(r)Patch cardiac monitoring device can efficiently characterize symptomatic
      patients without significant arrhythmia and has a higher diagnostic yield for
      arrhythmias than traditional 24-48 hour Holter monitoring. It allows for longer
      term monitoring up to 14 days.

PMID- 24672612
TI  - Improving bariatric patient transport and care with simulation.
AB  - INTRODUCTION: Obesity is prevalent in the United States. Obese patients have
      physiologic differences from non-obese individuals. Not only does transport and
      maintenance of these patients require use of specialized equipment, but it also
      requires a distinct skill set and knowledge base. To date, there is no literature
      investigating simulation as a model for educating pre-hospital providers in the
      care of bariatric patients. The purpose of this study was to determine if a 3
      hour educational course with simulation could improve paramedics' knowledge and
      confidence of bariatric procedures and transport. This study also examined if
      prior experience with bariatric transport affected training outcomes. METHODS:
      Our study took place in August 2012 during paramedic training sessions.
      Paramedics completed a pre- and post-test that assessed confidence and knowledge
      and provided information on previous experience. They had a 30-minute didactic
      and participated in 2 20-minute hands-on skills portions that reviewed procedural
      issues in bariatric patients, including airway procedures, peripheral venous and
      intraosseous access, and cardiopulmonary resuscitation. Study participants took
      part in one of two simulated patient encounters. Paramedics were challenged with
      treating emergent traumatic and/or medical conditions, as well as extricating and
      transporting bariatric patients. Each group underwent a debriefing of the
      scenario immediately following their case. We measured confidence using a 5-point
      Likert-type response scale ranging from 1 (strongly disagree) to 5 (strongly
      agree) on a 7-item questionnaire. We assessed knowledge with 12 multiple choice
      questions. Paired-sample t-tests were used to compare pre- and post-simulation
      confidence and knowledge with a significance level of p<=0.05. We used analysis
      of covariance to examine the effect of previous experiences on pre-and post
      educational activity confidence and knowledge with a significance level of p
      <=0.05. Proportions and 95% confidence intervals are presented as appropriate. We
      determined the magnitude of significant pre-post differences with Cohen's d. We
      assessed scale reliability using Cronbach's alpha and was found to be reliable
      with scores of 0.83 and 0.88 across pre- and post-test responses, respectively.
      RESULTS: Participants exhibited a significant increase in confidence in
      performing procedures (p<0.01) and knowledge of bariatric patient management
      (p<0.001) after the simulation. The current study also found an increase in
      knowledge of transport, vascular access/circulation and airway management
      (p<0.001). Participant background showed no effects on these changes. CONCLUSION:
      This study suggests that simulation paired with a didactic is an effective method
      of education for paramedics caring for and transporting bariatric patients. The
      data show a significant increase in knowledge and confidence with a 3-hour
      training session, irrespective of previous training or experience with bariatric
      patients. This is the first study of its kind to apply simulation training for
      the pre-hospital care of bariatric patients.

PMID- 24672613
TI  - Staff perceptions of an on-site clinical pharmacist program in an academic
      emergency department after one year.
AB  - INTRODUCTION: Emergency department clinical pharmacists (EPh) serve a relatively
      new clinical role in emergency medicine. New EPh may still face barriers prior to
      working in the emergency department (ED), including staff acceptance. We aimed to
      assess staff perceptions of a university hospital EPh program 1 year after
      implementation. METHODS: We sent an electronic survey consisting of 7 multiple
      choice questions, 17 5-point Likert-scale questions, and 1 free-text comment
      section to ED providers and nurses. The qualitatively validated survey assessed
      staff's general perceptions of the EPh and their clinical work. RESULTS: We
      received responses from 14 attending physicians, 34 emergency medicine residents,
      5 mid-level providers, and 51 nurses (80% response rate). Overall, the ED staff
      strongly supported the presence of an EPh. All of the respondents consulted the
      EPh at least once in their previous 5 ED shifts. Most respondents (81%) felt the
      EPh's availability for general consultation and aid during resuscitations served
      as the major contribution to medication and patient safety. The participants also
      expressed that they were more likely to consult a pharmacist when they were
      located in the ED, as opposed to having to call the main pharmacy. CONCLUSION:
      The EPh model of practice at our institution provides valuable perceived benefit
      to ED providers.

PMID- 24672614
TI  - Depression, suicidal ideation, and suicidal attempt presenting to the emergency
      department: differences between these cohorts.
AB  - INTRODUCTION: The World Health Organization estimates that one million people die
      by suicide every year. Few studies have looked at factors associated with
      disposition in patients with chief complaints of depression, suicidal ideation
      (SI) and suicidal attempts (SA) who present to the emergency department (ED). Our
      objective was to assess individual determinants associated with ED disposition of
      patients in depressed patients presenting to the ED. METHODS: We conducted a
      retrospective study using the National Hospital Ambulatory Medical Care Survey
      from 2006 to 2008. We used logistic regression to identify factors associated
      with discharge, in SI, SA and depression patients. Independent variables included
      socio-demographic information, vital signs, mode of arrival, insurance status,
      place of residence and concomitant psychiatric diagnosis. RESULTS: Of the 93,030
      subjects, 2,314 met the inclusion criteria (1,362 depression, 353 SI and 599 SA).
      Patients who arrived by ambulance were less likely to be discharged (odds ratio
      [OR] 0.63, 95% confidence interval [CI] 0.43-0.92). Hispanic patients and
      patients age 15 to 29 were likely to be discharged (OR 1.61, 95% CI 1.16-2.24 and
      OR 1.55, 95% CI 1.15-2.10 respectively). Insurance status and housing status were
      not significantly associated patient was being discharge from EDs. CONCLUSION:
      The Hispanic population had higher discharge rates, but the reasons are yet to be
      explored. Patients with SA and SI are discharged less frequently than those with
      depression, regardless of insurance type or housing status.

PMID- 24672615
TI  - Prospective analysis of single operator sonographic optic nerve sheath diameter
      measurement for diagnosis of elevated intracranial pressure.
AB  - INTRODUCTION: The accurate diagnosis of elevated intracranial pressure (eICP) in
      the emergent setting is a critical determination that presents significant
      challenges. Several studies show correlation of sonographic optic nerve sheath
      diameter (ONSD) to eICP, while others show high inter-observer variability or
      marginal performance with less experienced sonographers. The objective of our
      study is to assess the ability of bedside ultrasound measurement of ONSD to
      identify the presence of eICP when performed by a single experienced sonographer.
      We hypothesize that ONSD measurement is sensitive and specific for detecting eICP
      and can be correlated with values obtained by external ventricular device (EVD).
      METHODS: This was a prospective blinded observational study conducted in a
      neurocritical care unit of a level 1 trauma center. ONSD measurement was
      performed on a convenience sample of 27 adult patients who required placement of
      an invasive intracranial monitor as part of their clinical care. One certified
      sonographer/physician performed all ultrasounds within 24 hours of placement of
      EVD. The sonographer was blinded to the ICP recorded by invasive monitor at the
      time of the scan. A mean ONSD value of >=5.2 mm was taken as positive. RESULTS:
      The sonographer performed 27 ocular ultrasounds on individual patients. Six (22%)
      of these patients had eICP (EVD measurement of >20 mmHg). Spearman rank
      correlation coefficient of ONSD and ICP was 0.408 (p=0.03), demonstrating a
      moderate positive correlation. A ROC curve was created to determine the optimal
      cut off value to distinguish an eICP greater than 20 mmHg. The area under the
      receiver operator characteristic curve was 0.8712 (95% confidence interval
      [CI]=0.67 to 0.96). ONSD >=5.2 mm was a good predictor of eICP (>20 mmHg) with a
      sensitivity of 83.3% (95% CI=35.9% to 99.6%) and specificity of 100% (95%
      CI=84.6% to 100%). CONCLUSION: While the study suggests ONSD measurements
      performed by a single skilled operator may be both sensitive and specific for
      detecting eICP, confirmation in a much larger sample is needed. Ocular ultrasound
      may provide additional non-invasive means of assessing eICP.

PMID- 24672617
TI  - Dysuria in the emergency department: missed diagnosis of Chlamydia trachomatis.
AB  - INTRODUCTION: The clinical presentation of genital Chlamydia trachomatis
      infection (chlamydia) in women is often indistinguishable from a urinary tract
      infection. While merited in the setting of dysuria, emergency department (ED)
      clinicians do not routinely test for chlamydia in women. The primary aim of our
      study was to evaluate the frequency of chlamydia testing among women presenting
      to the ED with dysuria. METHODS: We conducted a retrospective chart review of
      women 19-25 years of age presenting with dysuria to an urban ED and who had been
      coded with urinary tract infection (UTI) as their primary diagnosis (ICD-9 599.0)
      from October 2005 to March 2011. We excluded women who were pregnant, had
      underlying anatomical or neurological urinary system pathology, had continuation
      of symptoms from UTI or a sexually transmitted infection (STI) diagnosed
      elsewhere, or were already on antibiotics for a UTI or STI. We identified the
      rates of sexual history screening, pelvic examination and chlamydia assay testing
      and evaluated predictors using univariate and multivariate analyses. RESULTS: Of
      280 women with dysuria and a UTI diagnosis, 17% were asked about their sexual
      history, with 94% reporting recent sexual activity. Pelvic examination was
      performed in 23%. We were unable to determine the overall chlamydia prevalence as
      only 20% of women in the cohort were tested. Among the 20% of women tested for
      chlamydia infection, 21% tested positive. Only 42% of chlamydia-positive women
      were prescribed treatment effective for chlamydia (azithromycin or doxycycline)
      at their visit; the remaining were prescribed UTI treatment not effective against
      chlamydia. Predictors of sexual history screening included vaginal bleeding (OR
      5.4, 95% CI=1.5 to 19.6) and discharge (OR 2.8, 95% CI=1.1 to 6.9). Predictors of
      a pelvic examination being performed included having a complaint of vaginal
      discharge (OR 11.8, 95% CI=4.2 to 32.9), a sexual history performed (OR 2.5, 95%
      CI=1.1 to 5.8), abdominal pain (OR 2.2, 95% CI=1.1 to 4.4), or pelvic pain (OR
      15.3, 95% CI=2.5 to 92.2); a complaint of urinary frequency was associated with a
      pelvic examination not being performed (OR 0.34, 95% CI=0.13 to 0.86).
      CONCLUSION: Sexual histories, pelvic examinations, and chlamydia testing were not
      performed in the majority of women presenting with dysuria and diagnosed with UTI
      in the ED. The performance of a sexual history along with the availability of
      self-administered vaginal swab and first-void urine-based chlamydia tests may
      increase identification of chlamydia infection in women with dysuria.

PMID- 24672616
TI  - Visual estimation of bedside echocardiographic ejection fraction by emergency
      physicians.
AB  - INTRODUCTION: The objective of this study was to determine whether bedside visual
      estimates of left ventricular systolic function (LVSF) by emergency physicians
      (EP) would agree with quantitative measurement of LVSF by the modified Simpson's
      method (MSM), as recommended by the American Society of Echocardiography.
      METHODS: After limited focused training, 2 trained EPs performed bedside
      echocardiography (BECH) procedures s between January and June 2012 to
      prospectively evaluate patients presenting to the emergency department (ED) with
      dyspnea. EPs categorized their visually estimated ejection fractions (VEF) as
      either low or normal. Formal echocardiography were ordered and performed by an
      experienced cardiologist using the MSM and accepted as the criterion standard. We
      compared BECH results for each EP using chi-squared testing and performed
      correlation analysis by Pearson correlation coefficient. RESULTS: Of the 146
      enrolled patients with dyspnea, 13 were excluded and 133 were included in the
      study. Comparison of EPs vs. cardiologist's estimate of ejection fraction yielded
      a Pearson's correlation coefficient of 0.77 (R, p<0.0001) and 0.78 (R, p<0.0001).
      Calculated biserial correlations using point-biserial correlation and z-scores
      were 1 (rb, p<0.0001) for both EPs. The agreement between EPs and the
      cardiologist was 0.861 and 0.876, respectively. The sensitivity, specificity,
      positive predictive value, negative predictive value, and the positive and
      negative likelihood ratios for each physician were 98.7-98.7%, 86.2-87.9%, 0.902
      0.914, 0.980-0.981, 7.153-8.175, 0.015-0.015, respectively. CONCLUSION: EPs with
      a focused training in limited BECH can assess LVSF accurately in the ED by visual
      estimation.

PMID- 24672618
TI  - Tackling the global challenge: humanitarian catastrophes.
AB  - "Humanitarian catastrophes," conflicts and calamities generating both widespread
      human suffering and destructive events, require a wide range of emergency
      resources. This paper answers a number of questions that humanitarian
      catastrophes generate: Why and how do the most-developed countries-those with the
      resources, capabilities, and willingness to help-intervene in specific types of
      disasters? What ethical and legal guidelines shape our interventions? How well do
      we achieve our goals? It then suggests a number of changes to improve
      humanitarian responses, including better NGO-government cooperation, increased
      research on the best disaster response methods, clarification of the criteria and
      roles for humanitarian (military) interventions, and development of post-2015
      Millennium Development Goals with more accurate progress measures. 

PMID- 24672619
TI  - Onset and duration of intravenous and intraosseous rocuronium in swine.
AB  - INTRODUCTION: The intraosseous (IO) route has become a popular method to gain
      access to the peripheral circulation in emergency situations. Despite little
      supporting data, it is generally believed that IO absorption is immediate and
      equivalent to the intravenous (IV) route. It is important to determine if
      rocuronium can effectively be administered by the IO route. The aim of the study
      was to determine and compare the onset and duration of rocuronium when
      administered via the IO and IV routes in a normovolemic pig model. METHODS: We
      recorded electromyographic (EMG) data following tibial IO and peripheral IV
      administration of rocuronium (1.2 mg/kg) in 10 swine weighing between 56 and 71
      Kg. We transformed data were transformed to percent of baseline, determined onset
      and recovery characteristics. RESULTS: The onset EMG-time profiles for IO and IV
      administration were very similar: tibial IO compared to IV administration did not
      statistically alter the onset of paralysis. The IO group took statistically
      longer than the IV group to return to 50 (p=0.042), 75 (p=0.034) and 95 (p=0.036)
      percent of baseline activity. CONCLUSION: The duration of effect is statistically
      longer after IO administration but is more of an academic interest than a
      clinical concern. The results of this study suggest that rocuronium can
      effectively be administered via the IO route without the need for dose
      adjustments.

PMID- 24672620
TI  - The effect of compressor-administered defibrillation on peri-shock pauses in a
      simulated cardiac arrest scenario.
AB  - INTRODUCTION: Coordination of the tasks of performing chest compressions and
      defibrillation can lead to communication challenges that may prolong time spent
      off the chest. The purpose of this study was to determine whether defibrillation
      provided by the provider performing chest compressions led to a decrease in peri
      shock pauses as compared to defibrillation administered by a second provider, in
      a simulated cardiac arrest scenario. METHODS: This was a randomized, controlled
      study measuring pauses in chest compressions for defibrillation in a simulated
      cardiac arrest model. We approached hospital providers with current CPR
      certification for participation between July, 2011 and October, 2011. Volunteers
      were randomized to control (facilitator-administered defibrillation) or
      experimental (compressor-administered defibrillation) groups. All participants
      completed one minute of chest compressions on a mannequin in a shockable rhythm
      prior to administration of defibrillation. We measured and compared pauses for
      defibrillation in both groups. RESULTS: Out of 200 total participants, we
      analyzed data from 197 defibrillations. Compressor-initiated defibrillation
      resulted in a significantly lower pre-shock hands-off time (0.57 s; 95% CI: 0.47
      0.67) compared to facilitator-initiated defibrillation (1.49 s; 95% CI: 1.35
      1.64). Furthermore, compressor-initiated defibrillation resulted in a
      significantly lower peri-shock hands-off time (2.77 s; 95% CI: 2.58-2.95)
      compared to facilitator-initiated defibrillation (4.25 s; 95% CI: 4.08-4.43).
      CONCLUSION: Assigning the responsibility for shock delivery to the provider
      performing compressions encourages continuous compressions throughout the
      charging period and decreases total time spent off the chest. However, as this
      was a simulation-based study, clinical implementation is necessary to further
      evaluate these potential benefits.

PMID- 24672621
TI  - Finite element modeling of the viscoelastic responses of the eye during
      microvolumetric changes.
AB  - A linear viscoelastic finite element model was built to investigate factors that
      influenced the intraocular pressure (IOP) elevations due to micro-volumetric
      changes in the eye at three different rates. The viscoelastic properties of the
      cornea and the sclera, including the instantaneous modulus, equilibrium modulus,
      and relaxation time constants, parametrically varied to examine their effects on
      IOP elevations at different rates of volumetric changes. The simulated responses
      were in good agreement with the previously reported experimental results obtained
      from porcine globes, showing the general trend of higher IOP elevations at faster
      rates. The simulations showed that all viscoelastic properties influenced the
      profile of the dynamic IOP due to volumetric changes, and the relative
      significance of a specific parameter was highly dependent on the rate of change.

PMID- 24672622
TI  - [Visual prognosis and refractive outcome after congenital cataract surgery with
      primary implantation: a study of a series of 108 cases].

PMID- 24672623
TI  - [Dorsal elastofibroma: retrospective study of 21 cases and review of literature].

PMID- 24672624
TI  - Per operative discovery of placenta praevia percreta: a case report.
AB  - Placenta percreta is a rare pathological entity with challenging diagnostic and
      therapeutic requirements especially for resource limited settings. We present
      here the case of a 40 year old woman with a per operative diagnosis of placenta
      accreta during a caesarian section indicated for placenta praevia. We highlight
      the diagnostic and therapeutic difficulties associated with this condition
      especially in low resource settings. Physicians performing caesarian sections
      should be prepared for complex intra-operative findings in high risk patients. 

PMID- 24672625
TI  - Enlarging back mass on a 33-year-old man.

PMID- 24672626
TI  - [Post-traumatic diaphragmatic hernia in children: about a case at the University
      Hospital Pediatric Charles de Gaulle of Ouagadougou].

PMID- 24672627
TI  - [Generalized bullous lupus: a rare initial presentation of systemic lupus
      erythematosus].

PMID- 24672628
TI  - Postpartum hemoperitoneum due to rupture of a blood vessel on a uterine pseudo
      tumor: a case report.
AB  - We are reporting a case of hemoperitoneum followed by early post partum collapse
      due to bleeding from a ruptured vessel on the surface of an undiagnosed uterine
      pseudo tumor. There are literature reports of spontaneous hemoperitoneum from
      bleeding of superficial vessels over lying myomas during pregnancy but a case of
      rupture of a blood vessel on a uterine pseudo tumor leading to isolated
      hemoperitoneum in the immediate postpartum period is a rare event. We are
      presenting the literature review and some aspects of the management of this case.
      The importance of having a high index of suspicion in cases of hemoperitoeum
      occurring immediately after delivery especially in a low income setting where
      radiologic imaging techniques like magnetic resonance imaging (MRI); which is the
      most sensitive diagnostic tool in cases of ruptured vessels are rare is
      highlighted. 

PMID- 24672629
TI  - [The primary melanoma of the female genital tract: report of three cases and
      review of literature].

PMID- 24672630
TI  - [The multiple thoracic actinomycosis in immunocompetent subjects].

PMID- 24672631
TI  - Listening to the voices: an exploratory study of the experiences of women
      diagnosed and living with breast cancer in Uganda.
AB  - INTRODUCTION: Breast cancer is one of the leading causes of cancer deaths amongst
      Ugandan women. Most women live through challenging and emotional experiences
      having been diagnosed with breast cancer. The purpose of this study was to
      explore the lived experiences of women diagnosed and living with breast cancer.
      METHODS: This was an exploratory qualitative study using a convenience sample (n
      = 12) of women confirmed with breast cancer and reporting to the Radiology
      department for imaging. In-depth individual interviews were conducted and
      findings were summarized into themes, representative of the participants' lived
      experiences. RESULTS: All women in this study initially went through emotional
      trauma of living with breast cancer. However, with time, they seemed to accept
      and cope with their situation. Four major themes summarizing their experiences
      included: Thought of Death, Strength to live, Loss of female identity and
      sexuality and Coping mechanisms. CONCLUSION: This study provided a unique insight
      of the experiences of women living with breast cancer. By listening to their
      narratives, one could see emotional pain, anger, anxiety, strength to live and
      many more. Although women with breast cancer get clinical management, there is
      need to design holistic palliative healthcare services including counseling to
      assist then cope with life.

PMID- 24672632
TI  - Mangifera indica fruit extract improves memory impairment, cholinergic
      dysfunction, and oxidative stress damage in animal model of mild cognitive
      impairment.
AB  - To date, the effective preventive paradigm against mild cognitive impairment
      (MCI) is required. Therefore, we aimed to determine whether Mangifera indica
      fruit extract, a substance possessing antioxidant and cognitive enhancing
      effects, could improve memory impairment, cholinergic dysfunction, and oxidative
      stress damage in animal model of mild cognitive impairment. Male Wistar rats,
      weighing 180-200 g, were orally given the extract at doses of 12.5, 50, and 200
      mg . kg(-1) BW for 2 weeks before and 1 week after the bilateral injection of
      AF64A (icv). At the end of study, spatial memory, cholinergic neurons density,
      MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were
      determined. The results showed that all doses of extract could improve memory
      together with the decreased MDA level and the increased SOD and GSH-Px enzymes
      activities. The increased cholinergic neurons density in CA1 and CA3 of
      hippocampus was also observed in rats treated with the extract at doses of 50 and
      200 mg . kg(-1) BW. Therefore, our results suggested that M. indica, the
      potential protective agent against MCI, increased cholinergic function and the
      decreased oxidative stress which in turn enhanced memory. However, further
      researches are essential to elucidate the possible active ingredients and detail
      mechanism.

PMID- 24672633
TI  - Copper and copper proteins in Parkinson's disease.
AB  - Copper is a transition metal that has been linked to pathological and beneficial
      effects in neurodegenerative diseases. In Parkinson's disease, free copper is
      related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy
      body formation. Decreased copper along with increased iron has been found in
      substantia nigra and caudate nucleus of Parkinson's disease patients. Copper
      influences iron content in the brain through ferroxidase ceruloplasmin activity;
      therefore decreased protein-bound copper in brain may enhance iron accumulation
      and the associated oxidative stress. The function of other copper-binding
      proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent
      neurodegeneration. Copper may regulate neurotransmission since it is released
      after neuronal stimulus and the metal is able to modulate the function of NMDA
      and GABA A receptors. Some of the proteins involved in copper transport are the
      transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited
      information about the role of those biomolecules in the pathophysiology of
      Parkinson's disease; for instance, it is known that CTR1 is decreased in
      substantia nigra pars compacta in Parkinson's disease and that a mutation in
      ATP7B could be associated with Parkinson's disease. Regarding copper-related
      therapies, copper supplementation can represent a plausible alternative, while
      copper chelation may even aggravate the pathology. 

PMID- 24672636
TI  - Dietary polyphenols and their effects on cell biochemistry and pathophysiology
      2013.

PMID- 24672634
TI  - Lack of association between nuclear factor erythroid-derived 2-like 2 promoter
      gene polymorphisms and oxidative stress biomarkers in amyotrophic lateral
      sclerosis patients.
AB  - Oxidative stress involvement has been strongly hypothesized among the possible
      pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral
      sclerosis (ALS). The intracellular redox balance is finely modulated by numerous
      complex mechanisms critical for cellular functions, among which the nuclear
      factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a
      cohort of ALS patients (n = 145) and healthy controls (n = 168), three SNPs in
      Nrf2 gene promoter: -653 A/G, -651 G/A, and -617 C/A and evaluated, in a subset
      (n = 73) of patients, advanced oxidation protein products (AOPP), iron-reducing
      ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral
      biomarkers. Nrf2 polymorphisms were not different among patients and controls.
      Increased levels of AOPP (P < 0.05) and decreased levels of FRAP (P < 0.001) have
      been observed in ALS patients compared with controls, but no difference in -SH
      values was found. Furthermore, no association was found between biochemical
      markers of redox balance and Nrf2 polymorphisms. These data confirm an altered
      redox balance in ALS and indicate that, while being abnormally modified compared
      to controls, the oxidative stress biomarkers assessed in this study are
      independent from the -653 A/G, -651 G/A, and -617 C/A Nrf2 SNPs in ALS patients.

PMID- 24672635
TI  - Allyl isothiocyanate increases MRP1 function and expression in a human bronchial
      epithelial cell line.
AB  - Multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding
      cassette (ABC) superfamily of transporters, plays an important role in normal
      lung physiology by protecting cells against oxidative stress and toxic
      xenobiotics. The present study investigates the effects of allyl isothiocyanate
      (AITC) on MRP1 mRNA and MRP1 protein expression and transporter activity in the
      immortalised human bronchial epithelial cell line 16HBE14o-. MRP1 mRNA and MRP1
      protein expression in 16HBE14o- cells that were treated with allyl isothiocyanate
      were analysed by real-time PCR assay and Western blotting. The transport of
      carboxyfluorescein, a known MRP1 substrate, was measured by functional flow
      cytometry to evaluate MRP1 activity. Treatment with AITC at concentrations of 5
      40 MUM increased MRP1 protein levels in a concentration-dependent manner. AITC
      treatments at concentrations of 1-40 MUM caused concentration-dependent increases
      in MRP1 mRNA levels that were up to seven times greater than the levels found in
      control cells. Finally, AITC treatment at concentrations of 5-40 MUM
      significantly increased MRP1-dependent efflux in 16HBE14o- cells. These results
      suggest that AITC can increase the expression and activity of MRP1 in 16HBE14o-
      cells in a concentration-dependent manner. The upregulation of MRP1 activity and
      expression by AITC could produce therapeutic effects in the treatment of lung
      disease.

PMID- 24672637
TI  - Antiapoptotic actions of methyl gallate on neonatal rat cardiac myocytes exposed
      to H2O2.
AB  - Reactive oxygen species trigger cardiomyocyte cell death via increased oxidative
      stress and have been implicated in the pathogenesis of cardiovascular diseases.
      The prevention of cardiomyocyte apoptosis is a putative therapeutic target in
      cardioprotection. Polyphenol intake has been associated with reduced incidences
      of cardiovascular disease and better overall health. Polyphenols like
      epigallocatechin gallate (EGCG) can reduce apoptosis of cardiomyocytes, resulting
      in better health outcomes in animal models of cardiac disorders. Here, we
      analyzed whether the antioxidant N-acetyl cysteine (NAC) or polyphenols EGCG,
      gallic acid (GA) or methyl gallate (MG) can protect cardiomyocytes from cobalt or
      H2O2-induced stress. We demonstrate that MG can uphold viability of neonatal rat
      cardiomyocytes exposed to H2O2 by diminishing intracellular ROS, maintaining
      mitochondrial membrane potential, augmenting endogenous glutathione, and reducing
      apoptosis as evidenced by impaired Annexin V/PI staining, prevention of DNA
      fragmentation, and cleaved caspase-9 accumulation. These findings suggest a
      therapeutic value for MG in cardioprotection. 

PMID- 24672638
TI  - On the molecular pharmacology of resveratrol on oxidative burst inhibition in
      professional phagocytes.
AB  - Resveratrol-3,5,4'-trihydroxystilbene-possesses antioxidant activities in vitro.
      It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and
      lipid peroxidation products in cell free systems. Oxidative burst of whole human
      blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration
      dependent way, indicating suppression of both receptor and nonreceptor activated
      chemiluminescence by resveratrol. Results from isolated human neutrophils
      revealed that resveratrol was active extracellularly as well as intracellularly
      in inhibiting the generation of reactive oxygen species. Liberation of ATP and
      analysis of apoptosis showed that in the concentration of 100 MUM, resveratrol
      did not change the viability and integrity of isolated neutrophils. Western blot
      analysis documented that resveratrol in concentrations of 10 and 100 MUM
      significantly decreased PMA-induced phosphorylation of PKC alpha/beta II. Dose
      dependent inhibition of nitrite production and iNOS protein expression in RAW
      264.7 cells indicated possible interference of resveratrol with reactive nitrogen
      radical generation in professional phagocytes. The results suggest that
      resveratrol represents an effective naturally occurring substance with potent
      pharmacological effect on oxidative burst of human neutrophils and nitric oxide
      production by macrophages. It should be further investigated for its
      pharmacological activity against oxidative stress in ischaemia reperfusion,
      inflammation, and other pathological conditions, particularly neoplasia.

PMID- 24672639
TI  - Contrast-induced nephropathy in aged critically ill patients.
AB  - BACKGROUND: Aging is associated with renal structural changes and functional
      decline. The attributable risk for renal dysfunction from radiocontrast agents in
      critically ill older patients has not been well established. METHODS: In this
      prospective study, we assessed the incidence of contrast-induced nephropathy
      (CIN) in critically ill patients with stable renal function who underwent
      computed tomography with intravenous contrast media. Patients were categorized
      into two age groups: <65 (YG) or >= 65 years old (OG). CIN was defined as 25% or
      greater increase from baseline of serum creatinine or as an absolute increase by
      0.5 mg/dL until the 5th day after the infusion of contrast agent. We also
      evaluated the alterations in oxidative stress by assessing serum 8-isoprostane.
      RESULTS: CIN occurred in 5 of 13 OG patients (38.46%) whereas no YG patient
      presented CIN (P = 0.015). Serum creatinine kinetics in older patients
      demonstrated a rise over five days following contrast infusion time while a
      decline was observed in the YG (P = 0.005). CONCLUSIONS: Older critically ill
      patients are more prone to develop renal dysfunction after the intravenous
      infusion of contrast agent in relation to their younger counterparts.

PMID- 24672640
TI  - Complications of radiofrequency ablation of hepatic tumors: Frequency and risk
      factors.
AB  - Radiofrequency ablation (RFA) has become an important option in the therapy of
      primary and secondary hepatic tumors. Surgical resection is still the best
      treatment option, but only a few of these patients are candidates for surgery:
      multilobar disease, insufficient liver reserve that will lead to liver failure
      after resection, extra-hepatic disease, proximity to major bile ducts and
      vessels, and co-morbidities. RFA has a low mortality and morbidity rate and is
      considered to be safe. Thus, complications occur and vary widely in the
      literature. Complications are caused by thermal damage, direct needle injury,
      infection and the patient's co-morbidities. Tumor type, type of approach, number
      of lesions, tumor localization, underlying hepatic disease, the physician's
      experience, associated hepatic resection and lesion size have been described as
      factors significantly associated with complications. The physician in charge
      should promptly recognize high-risk patients more susceptible to complications,
      perform a close post procedure follow-up and manage them early and adequately if
      they occur. We aim to describe complications from RFA of hepatic tumors and their
      risk factors, as well as a few techniques to avoid them. This way, others can
      decrease their morbidity rates with better outcomes. 

PMID- 24672642
TI  - Management of gastric variceal bleeding: Role of endoscopy and endoscopic
      ultrasound.
AB  - Gastric varices (GVs) are notorious to bleed massively and often difficult to
      manage with conventional techniques. This mini-review addresses endoscopic
      management principles for gastric variceal bleeding, including limitations of
      ligation and sclerotherapy and merits of endoscopic variceal obliteration. The
      article also discusses how emerging use of endoscopic ultrasound provides
      optimism of better diagnosis, improved classification, innovative management
      strategies and confirmatory tool for eradication of GVs. 

PMID- 24672641
TI  - Thyroid hormone analogues and derivatives: Actions in fatty liver.
AB  - Fatty liver or nonalcoholic fatty liver disease (NAFLD), a problem of increasing
      clinical significance and prevalence worldwide, is associated with increased risk
      for the development of cirrhosis and hepatocellular carcinoma. Although several
      therapeutic approaches can be used in the context of NAFLD, dietary and physical
      activities are still the most frequently used strategies. Some pharmacological
      agents show promising results although no conclusions can be drawn from recent
      clinical trials. Thyroid hormones [THs; thyroxine (T4) and 3,3',5-triiodo-L
      thyronine (T3)] coordinate a diverse array of physiological events during
      development and lipid/energy homeostasis and have some potentially therapeutic
      actions which include inducing weight loss, and lowering plasma cholesterol
      levels and tissue adiposity. The thyroid hormones exert their physiological
      effects by binding to specific nuclear receptors [thyroid hormone receptors (TR)]
      of which the TRbeta isoform is liver specific and has been considered a putative
      target for the treatment of dyslipidemia and fatty liver. In view of this, the
      aim of the review is (1) to provide an overview of the action of T3 on lipid
      metabolism with implications for liver steatosis and (2) to provide an update on
      the current knowledge concerning the administration of TRbeta selective
      thyromimetics (GC-1 and MB07811), as well as of 3,5-diiodo-L-thyronine and its
      novel functional analogue TRC150094 in animal models of overweight and related
      disorders including primarily fatty liver. 

PMID- 24672643
TI  - Role of intrahepatic innervation in regulating the activity of liver cells.
AB  - Liver innervation comprises sympathetic, parasympathetic and peptidergic nerve
      fibers, organized as either afferent or efferent nerves with different origins
      and roles. Their anatomy and physiology have been studied in the past 30 years,
      with different results published over time. Hepatocytes are the main cell
      population of the liver, making up almost 80% of the total liver volume. The
      interaction between hepatocytes and nerve fibers is accomplished through a wealth
      of neurotransmitters and signaling pathways. In this short review, we have taken
      the task of condensing the most important data related to how the nervous system
      interacts with the liver and especially with the hepatocyte population, how it
      influences their metabolism and functions, and how different receptors and
      transmitters are involved in this complex process. 

PMID- 24672644
TI  - Hepatoprotective effect of silymarin.
AB  - The use of medicinal plants in treating illnesses has been reported since
      ancestral times. In the case of hepatic diseases, several species such as Silybum
      marianum, Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to
      ameliorate hepatic lesions. Silymarin is a natural compound derived from the
      species Silybum marianum, which is commonly known as Milk thistle. This plant
      contains at least seven flavoligands and the flavonoid taxifolin. The
      hepatoprotective and antioxidant activity of silymarin is caused by its ability
      to inhibit the free radicals that are produced from the metabolism of toxic
      substances such as ethanol, acetaminophen, and carbon tetrachloride. The
      generation of free radicals is known to damage cellular membranes and cause
      lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to
      the antioxidant defense of the liver. It has also been shown that silymarin
      increases protein synthesis in hepatocytes by stimulating RNA polymerase I
      activity. A previous study on humans reported that silymarin treatment caused a
      slight increase in the survival of patients with cirrhotic alcoholism compared
      with untreated controls. 

PMID- 24672645
TI  - Khat (Catha Edulis) as a possible cause of autoimmune hepatitis.
AB  - AIM: To investigate the potential role of khat in triggering auto immune
      hepatitis. METHODS: Patients with a history of khat use and acute hepatitis were
      identified using the computer database in the hepatology department at the Royal
      Hallamshire Hospital. They were then assessed for probability of having
      autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria.
      RESULTS: Six patients were identified. All of them had presented with acute
      hepatitis on a background of khat. All were male and five of these patients were
      of Somali origin, while one patient was from Yemen. The patients were given
      points on the modified autoimmune hepatitis score which is based on their liver
      enzymes, autoimmune screen, exclusion of viral hepatitis alcohol and drugs,
      immunoglobulin levels and liver histology. The patients were given a score of -4
      for khat use due to its potential to cause drug induced liver injury. Five of
      these patients scored between 10 and 15 points, placing them in the probable
      group for having autoimmune hepatitis. All of these patients were treated with
      prednisolone and demonstrated a good response to immunosuppression. CONCLUSION:
      One possibile cause of hepatotoxicity with khat could be via triggering of
      autoimmune hepatitis in a genetically susceptible individual. Further studies are
      needed for confirmation.

PMID- 24672646
TI  - Nested stromal-epithelial tumour of the liver: An unusual liver entity.
AB  - Nested stromal-epithelial tumours (NSETs) of the liver have been reported to be
      extremely unusual primary hepatic neoplasms. To date, few cases have been
      described in the literature. NSETs have been defined as non-hepatocytic and non
      biliary tumours of the liver consisting of nests of epithelial and spindled
      cells, myofibroblastic stroma and variable intralesional calcification and
      ossification. Here, we report a case of a young female who underwent liver
      resection for a large hepatic lesion that proved to be a calcifying NSET on
      pathological examination. Details about the clinical and histopathological
      features of the tumour are reported. 

PMID- 24672647
TI  - The HCV Revolution Did Not Happen Overnight.
AB  - The progress in HCV therapy in the last three years is similar to the progress
      that took HIV therapy ~14 years. We are at the brink of approval for an all-oral
      drug combination that is dosed once daily as a single pill, has >95% efficacy,
      and is well tolerated. This article summarizes the path to this success and the
      challenges still ahead.

PMID- 24672648
TI  - Role of stenting in the palliation of gastroesophageal junction cancer: A brief
      review.
AB  - Gastroesophageal junction cancer has an increasing incidence in western
      countries. It is inoperable when first manifested in more than 50% of cases. So,
      palliation is the only therapeutic option for the advanced disease to relieve
      dysphagia and its consequences in weakened patients with an estimated mean
      survival under 6 mo. This article has tried to identify trends focusing on
      current information about the best palliative treatment, with an emphasis on the
      role of stenting. Self-expanding stent placement, either metal or plastic, is the
      main management option. However, this anatomical location creates some particular
      problems for stent safety and effectiveness which may be overcome by properly
      designed novel stents. The stents ensure a good quality of life and must be
      preferred over other alternative methods of loco-regional modalities, i.e.,
      external radiation, laser thermal or photodynamic therapy. Although stent
      placement is generally a simple, safe and effective method, there are sometimes
      complications, increasing the morbidity and mortality rate. Bypass operative
      procedures have now been abandoned as a first choice. The stomach instead of the
      colon must be used for a bypass operation when it is needed. Chemotherapy,
      despite the toxicity, and intraluminal radiation (brachytherapy) have a well
      defined role. 

PMID- 24672649
TI  - Giant mucinous cystic adenoma with pancreatic atrophy mimicking dorsal agenesis
      of the pancreas.
AB  - Mucinous cystic adenoma (MCA) of the pancreas is a rare benign cystic tumor with
      ovarian-like stroma and lack of communication with the pancreatic ductal system.
      The ovarian tissue is incorporated from the left gonad within the dorsal pancreas
      during embryogenesis. Consequently, congenital dorsal agenesis of the pancreas
      (DAP) cannot be associated with MCA. We report the case of a giant MCA associated
      with atrophy of the dorsal pancreas mimicking complete DAP. Pancreato-magnetic
      resonance imaging failed to identify the dorsal pancreas but the absence of
      diabetes mellitus and compression of the splenic vein with major tributaries
      rectified the diagnosis of secondary atrophy of the distal pancreas. Unusual
      proximal location of the cyst in the pancreas may have induced chronic
      obstruction of both the dorsal pancreatic duct and the splenic vein, with
      secondary atrophy of the distal pancreas. 

PMID- 24672650
TI  - Giant Meckel's diverticulum: An exceptional cause of intestinal obstruction.
AB  - Meckel's diverticulum (MD) results from incomplete involution of the proximal
      portion of the vitelline (also known as the omphalomesenteric) duct during weeks
      5-7 of foetal development. Although MD is the most commonly diagnosed congenital
      gastrointestinal anomaly, it is estimated to affect only 2% of the population
      worldwide. Most cases are asymptomatic, and diagnosis is often made following
      investigation of unexplained gastrointestinal bleeding, perforation, inflammation
      or obstruction that prompt clinic presentation. While MD range in size from 1-10
      cm, cases of giant MD (>= 5 cm) are relatively rare and associated with more
      severe forms of the complications, especially for obstruction. Herein, we report
      a case of giant MD with secondary small bowel obstruction in an adult male that
      was successfully managed by surgical resection and anastomosis created with
      endoscopic stapler device (80 mm, endo-GIA stapler). Patient was discharged on
      post-operative day 6 without any complications. Histopathologic examination
      indicated Meckel's diverticulitis without gastric or pancreatic metaplasia. 

PMID- 24672651
TI  - Coexistence of abdominal cocoon, intestinal perforation and incarcerated Meckel's
      diverticulum in an inguinal hernia: A troublesome condition.
AB  - Sclerosing encapsulating peritonitis (SEP) is a rare disease entity, in which the
      small intestine becomes encased and mechanically obstructed by a dense, fibrotic
      membrane. The disorder is characterized as either primary (idiopathic) or
      secondary to other causes. The idiopathic cases of SEP, which lack any
      identifiable etiology according to clinical, radiological and histopathological
      findings, are also reported under the designation of abdominal cocoon syndrome.
      The most frequent presenting symptoms of all SEP cases are nausea, vomiting,
      abdominal distention and inability to defecate, all of which are associated with
      the underlying intestinal obstruction. Persistent untreated SEP may advance to
      intestinal perforation, representing a life-threatening condition. However,
      preoperative diagnosis remains a particular clinical challenge, and most
      diagnoses are confirmed only when the typical fibrous membrane encasing the small
      intestine is discovered by laparotomy. Here, we report the clinical presentation
      of an 87-year-old male with signs of intestinal obstruction and the ultimate
      diagnosis of concurrent abdominal cocoon, right incarcerated Meckel's
      diverticulum, and gastrointestinal perforation in laparotomy. 

PMID- 24672652
TI  - Population screening for colorectal cancer means getting FIT: the past, present,
      and future of colorectal cancer screening using the fecal immunochemical test for
      hemoglobin (FIT).
AB  - Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which
      colorectal cancer (CRC) is screened. Although these tests are being performed
      worldwide, why is this test different from its predecessors? What evidence
      supports its adoption? How can this evidence best be used? This review addresses
      these questions and provides an understanding of FIT theory and practices to
      expedite international efforts to implement the use of FIT in CRC screening. 

PMID- 24672653
TI  - Immune response and the tumor microenvironment: how they communicate to regulate
      gastric cancer.
AB  - Gastric cancer is the second most common cause of cancer-related death in the
      world. A growing body of evidence indicates that inflammation is closely
      associated with the initiation, progression, and metastasis of many tumors,
      including those of gastric cancer. In addition, approximately 60% of the world's
      population is colonized by Helicobacter pylori, which accounts for more than 50%
      of gastric cancers. While the role of inflammation in intestinal and colonic
      cancers is relatively well defined, its role in stomach neoplasia is still
      unclear because of the limited access of pathogens to the acidic environment and
      the technical difficulties isolating and characterizing immune cells in the
      stomach, especially in animal models. In this review, we will provide recent
      updates addressing how inflammation is involved in gastric malignancies, and what
      immune characteristics regulate the pathogenesis of stomach cancer. Also, we will
      discuss potential therapeutics that target the immune system for the efficient
      treatment of gastric cancer. 

PMID- 24672654
TI  - Effects of DA-9701, a novel prokinetic agent, on phosphorylated extracellular
      signal-regulated kinase expression in the dorsal root ganglion and spinal cord
      induced by colorectal distension in rats.
AB  - BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis
      Tuber, is a new prokinetic agent that exhibits an analgesic effect on the
      abdomen. We investigated whether DA-9701 affects visceral pain induced by
      colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided
      into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C
      (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and
      phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root
      ganglion (DRG) and spinal cord was determined by immunohistochemical staining and
      Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord
      expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the
      group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK
      was lower than that in group B. Western blot results for p-ERK in the spinal cord
      indicated a higher level of expression in group B than in group A and a lower
      level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease
      visceral pain via the downregulation of p-ERK in the DRG and spinal cord.

PMID- 24672655
TI  - Fatigue severity and factors associated with high fatigue levels in Korean
      patients with inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Many patients with inflammatory bowel disease (IBD) often
      complain of fatigue. To date, only a few studies in Western countries have
      focused on fatigue related to IBD, and fatigue has never been specifically
      studied in Asian IBD patients. The aim of the present study was to investigate
      the fatigue level and fatigue-related factors among Korean IBD patients. METHODS:
      Patients in remission or with mild to moderate IBD were included. Fatigue was
      assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue and
      the Brief Fatigue Inventory. Corresponding healthy controls (HCs) also completed
      both fatigue questionnaires. RESULTS: Sixty patients with Crohn disease and 68
      patients with ulcerative colitis (UC) were eligible for analysis. The comparison
      group consisted of 92 HCs. Compared with the HCs, both IBD groups were associated
      with greater levels of fatigue (p<0.001). Factors influencing the fatigue score
      in UC patients included anemia and a high erythrocyte sedimentation rate (ESR).
      CONCLUSIONS: Greater levels of fatigue were detected in Korean IBD patients
      compared with HCs. Anemia and ESR were determinants of fatigue in UC patients.
      Physicians need to be aware of fatigue as one of the important symptoms of IBD to
      better understand the impact of fatigue on health-related quality of life.

PMID- 24672656
TI  - Endoscopic experience improves interobserver agreement in the grading of
      esophagitis by Los Angeles classification: conventional endoscopy and optimal
      band image system.
AB  - BACKGROUND/AIMS: Interobserver variation by experience was documented for the
      diagnosis of esophagitis using the Los Angeles classification. The aim of this
      study was to evaluate whether interobserver agreement can be improved by higher
      levels of endoscopic experience in the diagnosis of erosive esophagitis. METHODS:
      Endoscopic images of 51 patients with gastroesophageal reflux disease (GERD)
      symptoms were obtained with conventional endoscopy and optimal band imaging
      (OBI). Endoscopists were divided into an expert group (16 gastroenterologic
      endoscopic specialists guaranteed by the Korean Society of Gastrointestinal
      Endoscopy) and a trainee group (individuals with fellowships, first year of
      specialty training in gastroenterology). All endoscopists had no or minimal
      experience with OBI. GERD was diagnosed using the Los Angeles classification with
      or without OBI. RESULTS: The mean weighted paired kappa statistics for
      interobserver agreement in grading erosive esophagitis by conventional endoscopy
      in the expert group was better than that in the trainee group (0.51 vs 0.42,
      p<0.05). The mean weighted paired k statistics in the expert group and in the
      trainee group based on conventional endoscopy with OBI did not differ (0.42,
      0.42). CONCLUSIONS: Interobserver agreement in the expert group using
      conventional endoscopy was better than that in the trainee group. Endoscopic
      experience can improve the interobserver agreement in the grading of esophagitis
      using the Los Angeles classification.

PMID- 24672657
TI  - The risk factors and quality of life in patients with overlapping functional
      dyspepsia or peptic ulcer disease with gastroesophageal reflux disease.
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD), functional dyspepsia
      (FD), and peptic ulcer disease (PUD) impact the daily lives of affected
      individuals. The aim of this study was to compare the risk factors and impacts on
      life quality of overlapping FD or PUD in patients with GERD. METHODS: Data from
      patients diagnosed with GERD were collected between January and November 2009. FD
      was defined using the Rome III diagnostic criteria. The overlapping GERD-FD or
      GERD-PUD groups were classified as concomitant GERD and FD or peptic ulcers. The
      characteristics of these individuals were analyzed. RESULTS: There were 63, 48,
      and 60 patients in the GERD only, overlapping GERD-FD, and overlapping GERD-PUD
      groups, respectively. Significantly younger age, female gender, lower body weight
      and body mass index, and higher rates of tea consumption were noted in the GERD
      FD group. Patients in the GERD-FD group exhibited the lowest quality of life
      scores, both with respect to physical and mental health, on the Short Form 36
      domains. CONCLUSIONS: Patients with concomitant GERD and FD were more likely to
      be younger and female. Overlapping GERD and FD had the worst impact on the
      quality of life of the affected individuals.

PMID- 24672658
TI  - Symptom characteristics and psychosomatic profiles in different spectrum of
      gastroesophageal reflux disease.
AB  - BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is diagnosed based on
      symptoms of heartburn and regurgitation but is a heterogeneous condition which
      can be subclassified according to endoscopy and esophageal reflux monitoring. The
      aim of this study was to identify differences in demographic characteristics and
      reflux symptom patterns among patients with various spectrum of GERD. METHODS:
      Patients having weekly heartburn or acid regurgitation were classified into four
      pathophysiological subgroups according to endoscopy and pH monitoring: reflux
      esophagitis (RE), endoscopy-negative reflux disease with pathological reflux
      (PR+), hypersensitive esophagus (HE), and normal acid exposure with negative
      symptom association (pH-). RESULTS: A total of 195 patients were enrolled. The
      numbers of patients in the subgroups were: RE, 39.0%; PR+, 20.0%; HE, 10.3%; and
      pH-, 30.8%. Grossly, reflux symptom patterns and relieving/exacerbating factors
      did not differ between subgroups. Prevalence of extraesophageal syndrome was
      higher in patients with PR+ than in other groups. Overlapping functional
      dyspepsia was common in all groups. The SCL-90-R depression score was higher in
      PR+ patients than in RE patients (p<0.05). CONCLUSIONS: Demographic
      characteristics and reflux symptom patterns cannot differentiate pH- group from
      GERD subtypes. Esophageal pH monitoring could be considered for the initial
      evaluation of GERD in the tertiary referral setting.

PMID- 24672659
TI  - Relationship between the severity of diversion colitis and the composition of
      colonic bacteria: a prospective study.
AB  - BACKGROUND/AIMS: Diversion colitis is the inflammation of the excluded segment of
      the colon in patients undergoing ostomy. It has been suggested that a change in
      colonic flora may lead to colitis; however, direct evidence for this disease
      progression is lacking. The aim of this study was to evaluate the relationship
      between the severity of diversion colitis and the composition of colonic
      bacteria. METHODS: We used culture methods and polymerase chain reaction to
      analyze the colonic microflora of patients who underwent rectal cancer resection
      with or without diversion ileostomy. In the diversion group, we also evaluated
      the severity of colonoscopic and pathologic colitis before reversal. RESULTS:
      This study enrolled 48 patients: 26 in the diversion group and 22 in the control
      group. Significant differences were observed between the two groups in the levels
      of Staphylococcus (p=0.038), Enterococcus (p<0.001), Klebsiella (p<0.001),
      Pseudomonas (p=0.015), Lactobacillus (p=0.038), presence of anaerobes (p=0.019),
      and Bifidobacterium (p<0.001). A significant correlation between the severity of
      colitis and bacterial composition was only observed for Bifidobacterium (p=0.005,
      correlation coefficient=-0.531). CONCLUSIONS: The colonic microflora differed
      significantly between the diversion and control groups. Bifidobacterium was
      negatively correlated with the severity of diversion colitis.

PMID- 24672660
TI  - Clinical utility of plasma glypican-3 and osteopontin as biomarkers of
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: alpha-Fetoprotein (AFP) is the biomarker most widely used to
      detect hepatocellular carcinoma (HCC), despite its suboptimal diagnostic
      accuracy. Glypican-3 (GPC3) and osteopontin (OPN) are secreted glycoproteins that
      are reportedly associated with tumorigenesis and metastasis. This study was
      conducted to evaluate the clinical utility of using plasma GPC3 and OPN as
      diagnostic biomarkers for HCC. METHODS: We measured the plasma levels of GPC3 and
      OPN in 120 HCC and 40 chronic liver disease (CLD) patients via an enzyme-linked
      immunosorbent assay. The diagnostic accuracy of each tumor marker was evaluated
      using receiver operating characteristic (ROC) curve analysis. RESULTS: The GPC3
      levels in the HCC patients (75.8 ng/mL) were significantly higher (p=0.020) than
      the levels in patients with CLD (66.4 ng/mL). The area under the ROC curve
      (AUROC) values for GPC3 and OPN were 0.62 and 0.51, respectively. In subgroup
      analyses, including subgroups of HCC patients with low serum AFP and PIVKA II
      levels, the AUROC of GPC3 remained relatively high (0.66), and GPC3 showed a high
      sensitivity (62.1%) for detecting small HCC tumors. CONCLUSIONS: The plasma
      levels of GPC3 and OPN demonstrated low diagnostic accuracy for HCC. However,
      GPC3 may have a complementary role in diagnosing HCC in patients with
      nondiagnostic levels of conventional tumor markers and with small-sized tumors.

PMID- 24672661
TI  - The expression of programmed death-1 in circulating CD4+ and CD8+ T cells during
      hepatitis B virus infection progression and its correlation with clinical
      baseline characteristics.
AB  - BACKGROUND/AIMS: Programmed death-1 (PD-1) expression was investigated in CD4(+)
      and CD8(+) T cells from hepatitis B virus (HBV)-infected patients at the chronic
      hepatitis B (CHB) infection, liver cirrhosis (LC), and hepatocellular carcinoma
      (HCC) stages. METHODS: PD-1 expression in circulating CD4(+) and CD8(+) T cells
      was detected by flow cytometry. The correlations between PD-1 expression and HBV
      viral load, alanine aminotransaminase (ALT) levels and aspartate aminotransferase
      (AST) levels were analyzed using GraphPad Prism 5.0. RESULTS: PD-1 expression in
      CD4(+) and CD8(+) T cells was significantly increased in both the CHB group and
      advanced-stage group (LC plus HCC). In the CHB group, PD-1 expression in both
      CD4(+) and CD8(+) T cells was positively correlated with the HBV viral load, ALT,
      and AST levels. However, in the LC plus HCC group, significant correlations
      between PD-1 expression and the clinical parameters were nearly absent.
      CONCLUSIONS: PD-1 expression in peripheral CD4(+) and CD8(+) T cells is dynamic,
      changes with HBV infection progression, and is related to HBV viral load and
      liver function, especially in CHB. PD-1 expression could be utilized as a
      potential clinical indicator to determine the extent of virus replication and
      liver injury.

PMID- 24672662
TI  - Silencing of CXCR4 inhibits tumor cell proliferation and neural invasion in human
      hilar cholangiocarcinoma.
AB  - BACKGROUND/AIMS: To evaluate the expression of CXC motif chemokine receptor 4
      (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and
      to investigate the cell proliferation and frequency of neural invasion (NI)
      influenced by RNAi-mediated CXCR4 silencing. METHODS: An immunohistochemical
      technique was used to detect the expression of CXCR4 in 41 clinical tissues,
      including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of
      small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the
      hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression
      of CXCR4 was monitored by quantitative real time polymerase chain reaction and
      Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a
      perineural cell and hilar-CCA cell coculture migration assay. RESULTS: The
      expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There
      was a positive correlation between the expression of CXCR4 and lymph node
      metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell
      lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased
      cell proliferation. CONCLUSIONS: CXCR4 is likely correlated with clinical
      recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of
      human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising
      therapeutic target for hilar-CCA.

PMID- 24672663
TI  - Elevated hemoglobin A1c levels are associated with worse survival in advanced
      pancreatic cancer patients with diabetes.
AB  - BACKGROUND/AIMS: Pre-existing diabetes mellitus (DM) has been identified as an
      adverse prognostic variable associated with increased mortality in various
      cancers. Although DM and hyperglycemia are considered risk factors for pancreatic
      cancer (PC), antidiabetic treatments for patients with advanced PC have been
      overlooked. This study aimed to evaluate the impact of hemoglobin A1c (HbA1c)
      levels on PC survival. METHODS: We retrospectively reviewed the medical records
      of first-diagnosed patients with advanced PC who were admitted to Konkuk
      University Medical Center from 2005 to 2011. RESULTS: A total of 127 patients
      were enrolled, and there were 111 deaths (87.4%) within the 7-year observational
      period. The most common etiology was disease progression (n=108). DM before PC
      diagnosis was observed in 65 patients (51.1%), including 28 patients with new
      onset DM. The overall median survival times in patients with and without DM were
      198 and 263 days, respectively (p=0.091). Survival time according to HbA1c was
      significantly different between the <7.0% and >=7.0% groups (362 and 144 days,
      respectively; p=0.038). In the HbA1c >=7.0% group, the median overall survival
      time was 273 days for the metformin group and 145 days for the nonmetformin oral
      agent group; however, there was no significant difference between the two groups
      (p=0.058). CONCLUSIONS: A high HbA1c level may be associated with worse survival
      in patients with advanced PC with DM. Antidiabetic treatment, metformin in
      particular, was associated with an improved outcome.

PMID- 24672665
TI  - Focal thickening at the fundus of the gallbladder: computed tomography
      differentiation of fundal type adenomyomatosis and localized chronic
      cholecystitis.
AB  - BACKGROUND/AIMS: The objective of our study was to identify useful computed
      tomography (CT) findings for differentiating fundal type adenomyomatosis from
      localized chronic cholecystitis involving the fundus of the gallbladder. METHODS:
      We retrospectively identified cases of 41 patients with pathologically proven
      adenomyomatosis (n=21) or chronic cholecystitis (n=20) who had fundal thickening
      of the gallbladder on preoperative abdominal CT. Analysis of the CT findings
      included evaluation of the thickness, contour, border, intralesional cystic area,
      adjacent gallbladder wall thickening, presence of inner layer enhancement,
      enhancement grade, enhancement pattern, and presence of stones. Statistical
      analyses were performed using the Mann-Whitney U test and Fisher exact test.
      RESULTS: Oval contour, inner layer enhancement and intralesional cystic area were
      more frequently noted in adenomyomatosis than in chronic cholecystitis (p<0.05
      for each finding). Flat contour and adjacent gallbladder wall thickening were
      more frequently observed in chronic cholecystitis than in adenomyomatosis. No
      differences between adenomyomatosis and chronic cholecystitis in terms of the
      thickness, enhancement grade, enhancement pattern and presence of stones were
      apparent. CONCLUSIONS: CT may help to differentiate fundal type adenomyomatosis
      from localized chronic cholecystitis involving the fundus of the gallbladder.

PMID- 24672664
TI  - Severe bleeding and perforation are rare complications of endoscopic ultrasound
      guided fine needle aspiration for pancreatic masses: an analysis of 3,090
      patients from 212 hospitals.
AB  - BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is
      useful for the pathological diagnosis of pancreatic masses, but patients are
      susceptible to severe bleeding and perforation. Because the incidence and
      severity of these complications have not been fully evaluated. METHODS: We aimed
      to evaluate severe bleeding and perforation after EUS-FNA for pancreatic masses
      using large-scale data derived from a Japanese nationwide administrative
      database. RESULTS: In total, 3,090 consecutive patients from 212 low- to high
      volume hospitals were analyzed. Severe bleeding requiring transfusion or
      endoscopic treatment occurred in seven patients (0.23%), and no perforation was
      observed. No patient mortality was recorded within 30 days of EUS-FNA. The rate
      of severe bleeding in low-volume hospitals was significantly higher than that in
      medium- and high-volume hospitals (0.48% vs 0.10%, p=0.045). CONCLUSIONS: Severe
      bleeding and perforation following EUS-FNA for pancreatic masses are rare, and
      the procedure is safe.

PMID- 24672666
TI  - A patient with eosinophilic gastroenteritis presenting with acute pancreatitis
      and ascites.
AB  - Eosinophilic gastroenteritis (EGE) is a rare disease characterized by focal or
      diffuse eosinophilic infiltration of the gastrointestinal tract, especially the
      stomach and duodenum. EGE has vague, nonspecific symptoms, including nausea,
      vomiting, abdominal pain, diarrhea, weight loss, ascites, and malabsorption.
      Here, we report a patient with EGE presenting with concurrent acute pancreatitis
      and ascites. A 68-year-old woman was admitted with abdominal pain, nausea,
      vomiting, and watery diarrhea. Laboratory findings revealed elevated serum titers
      of amylase, lipase, and peripheral blood eosinophil count. An abdominopelvic
      computed tomography scan showed a normal pancreas, moderate amount of ascites,
      and duodenal thickening. A esophagogastroduodenoscopy showed patchy erythematous
      mucosal lesions in the 2nd portion of the duodenum. Biopsies from the duodenum
      indicated eosinophilic infiltration in the lamina propria. The patient was
      successfully treated with prednisolone and montelukast. Despite its unusual
      occurrence, EGE may be considered in the differential diagnosis of unexplained
      acute pancreatitis, especially in a patient with duodenal edema on imaging or
      peripheral eosinophilia. 

PMID- 24672667
TI  - Comments to prediction of advanced fibrosis in nonalcoholic fatty liver disease:
      an enhanced model of BARD score.

PMID- 24672669
TI  - Shortening the length of stay and mechanical ventilation time by using positive
      suggestions via MP3 players for ventilated patients.
AB  - Long stay in intensive care unit (ICU) and prolonged ventilation are deleterious
      for subsequent quality of life and surcharge financial capacity. We have already
      demonstrated the beneficial effects of using suggestive communication on recovery
      time during intensive care. The aim of our present study was to prove the same
      effects with standardized positive suggestive message delivered by an MP3 player.
      Patients ventilated in ICU were randomized into a control group receiving
      standard ICU treatment and two groups with a standardized pre-recorded material
      delivered via headphones: a suggestive message about safety, self-control, and
      recovery for the study group and a relaxing music for the music group. Groups
      were similar in terms of age, gender, and mortality, but the SAPS II scores were
      higher in the study group than that in the controls (57.8 +/- 23.6 vs. 30.1 +/-
      15.5 and 33.7 +/- 17.4). Our post-hoc analysis results showed that the length of
      ICU stay (134.2 +/- 73.3 vs. 314.2 +/- 178.4 h) and the time spent on ventilator
      (85.2 +/- 34.9 vs. 232.0 +/- 165.6 h) were significantly shorter in the study
      group compared to the unified control. The advantage of the structured positive
      suggestive message was proven against both music and control groups. 

PMID- 24672668
TI  - The central role of extracellular vesicles in the mechanisms of thrombosis in
      paroxysmal nocturnal haemoglobinuria: a review.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired disorder of the
      haematopoietic stem cell that makes blood cells more sensitive to the action of
      complement. PNH patients experience an increased risk of arterial and venous
      thrombosis - major causes of death due to this disease. Though many potential
      interlaced mechanisms are suspected, extracellular vesicles (EVs) of various
      origins may play a central role. The processes possibly involved are haemolysis,
      platelet activation, injured endothelial cells and monocyte activation. The
      impact of transfusion should be evaluated. A better understanding of the
      mechanisms involved may help to propose guidelines for the prophylaxis and
      treatment of thrombosis in PNH. In this paper, we propose an updated review of
      the pathophysiology of the underlying mechanisms of thrombosis associated with
      PNH, with specific focus on the prominent role of EVs. 

PMID- 24672670
TI  - Recurrence of primary sclerosing cholangitis after liver transplantation - The
      Hungarian experience.
AB  - INTRODUCTION: Recurrence of primary sclerosing cholangitis (rPSC) after liver
      transplantation (OLT) significantly affects long-term graft survival. We aimed to
      evaluate the incidence of rPSC and clinical data of these patients in Hungary.
      PATIENTS AND METHODS: We retrospectively analyzed data of 511 whole liver
      transplantations from 1995 to 2011. During the study period, 49 OLTs were
      performed in 43 adult patients with end-stage PSC (10%). RESULTS: Out of 49 OLT,
      24 cases were excluded, rPSC was diagnosed in six patients (12%). Patients with
      rPSC had significantly higher mortality (p = 0.009) and graft loss (p = 0.009) in
      comparison to patients without recurrent disease. Younger recipient age, higher
      donor BMI was observed in the rPSC group. One patient was diagnosed with de novo
      IBD, the remaining five patients had worsening IBD activity in the posttransplant
      period. PreOLT colectomy was performed in 21% of the control and none of the rPSC
      group. PostOLT colectomy was performed in two rPSC patients due to severe therapy
      resistant colitis. CONCLUSIONS: Recurrent PSC significantly affects long-term
      mortality and graft loss. Younger age at OLT, higher donor BMI and severe active
      IBD may be associated with PSC recurrence. PreOLT total colectomy might have
      protective effect against rPSC.

PMID- 24672671
TI  - Advantages of a workbench reshaped AR1 mod catheter for right coronary
      angiography by right radial approach.
AB  - Transradial approach in cardiac catheterization is increasing. In daily practice,
      coronary angiography via radial artery is usually performed by using catheters
      designed for femoral approach. The aim of this study was to evaluate advantages
      in the use of a workbench reshaped AR1 mod catheter, in terms of procedural
      duration time, number of catheters per procedure, fluoroscopy time, contrast
      agent administered volume, images quality and costs. Two hundred patients,
      submitted to coronary angiography via right radial artery in our institution,
      have been retrospectively reviewed. Patients have been divided in two groups,
      depending on whether a workbench reshaped Cordis Amplatz AR1 mod catheter (rAR1
      mod), or catheters in their original shape (OC) have been employed. In the rAR1
      mod group (100 patients) a lower number of catheters per procedure (1.07 +/- 0.25
      vs. 1.47 +/- 1.65; p < 0.001), a more frequent right coronary selective
      engagement (76.76% vs. 53.12%; p < 0.001), a smaller amount of contrast agent
      (63.02 +/- 27.77 vs. 80.85 +/- 29.22 ml, p < 0.001), a reduced fluoroscopy and
      global procedural time (4.19 +/- 2.91 vs. 5.69 +/- 3.85 min, p = 0.004; and 34.58
      +/- 17.05 vs. 42.58 +/- 17.26 min, p = 0.001, respectively) were observed.
      According to our experience, when right coronary angiography via right radial
      approach is performed, the utilization of rAR1 mod catheter correlates with
      multiple advantages in terms of procedural parameters. 

PMID- 24672673
TI  - 'Electrical exclusion' of a critical myocardial mass by extended pulmonary vein
      antrum isolation for persistent atrial fibrillation treatment.
AB  - The aim of the study was to compare the efficacy of pulmonary vein antrum
      isolation (PVAI), extended PVAI and ganglionic plexi (GP) ablation in persistent
      AF. METHODS: One hundred and twenty patients 56.2 +/- 8.8 years old were
      randomized into three groups: GP ablation (n = 37), PVAI (n = 42), and extended
      PVAI (n = 41). The following parameters were studied: sinus rhythm restoration,
      vagal reactions, fluoroscopy time, procedure duration, lesion surface area. In 16
      months after the procedure, echocardiography and Holter monitoring were
      performed. RESULTS: Significant differences were found in the amount of X-ray
      exposure, procedure duration, lesion surface area and vagal reactions. In all the
      cases, atrial mechanical function worsened after the procedure. However, there
      were no significant differences between the groups. Sixteen months after the
      procedure, sinus rhythm without antiarrhythmic therapy was maintained in 38% of
      patients in GP group, in 56% of patients in PVAI group and in 69% of patients in
      extended PVAI group. CONCLUSIONS: In persistent AF, the extended PVAI is more
      effective than PVAI and GP ablation. After the PVAI or extended PVAI,
      abnormalities of the left atrial mechanical function occurred if the lesion area
      exceeded 25% of the total LA surface area.

PMID- 24672672
TI  - Comparative cath-lab assessment of coronary stenosis by radiology technician,
      junior and senior interventional cardiologist in patients treated with coronary
      angioplasty.
AB  - BACKGROUND: Exact quantification of plaque extension during coronary angioplasty
      (PCI) usually falls on interventional cardiologist (IC). Quantitative coronary
      stenosis assessment (QCA) may be possibly committed to the radiology technician
      (RT), who usually supports cath-lab nurse and IC during PCI. We therefore sought
      to investigate the reliability of QCA performed by RT in comparison with IC.
      METHODS: Forty-four consecutive patients with acute coronary syndrome underwent
      PCI; target coronary vessel size beneath target coronary lesion (S) and target
      coronary lesion length (L) were assessed by the RT, junior IC (JIC), and senior
      IC (SIC) and then compared. SIC evaluation, which determined the final stent
      selection for coronary stenting, was considered as a reference benchmark.
      RESULTS: RT performance with QCA support in assessing target vessel size and
      target lesion length was not significantly different from SIC (r = 0.46, p <
      0.01; r = 0.64, p < 0.001, respectively) as well as JIC (r = 0.79, r = 0.75, p <
      0.001, respectively). JIC performance was significantly better than RT in
      assessing target vessel size (p < 0.05), while not significant when assessing
      target lesion length. CONCLUSIONS: RT may reliably assess target lesion by using
      adequate QCA software in the cath-lab in case of PCI; RT performance does not
      differ from SIC.

PMID- 24672674
TI  - A dynamic sign of alveolar consolidation in bedside ultrasonography: Air
      bronchogram.
AB  - Acute dyspnoea is one of the most common reasons patients present to the
      emergency department (ED). In most cases, the physical examination and bedside
      radiographs are inconclusive, resulting in the need for more sophisticated
      diagnostics. These diagnostics may delay treatment or expose the patient to
      unnecessary radiation. Here, we present the case of a dyspnoeic patient. The
      patient was diagnosed with pneumonia by bedside thoracic ultrasonography (TUS).
      TUS was performed by the emergency physician and revealed bilateral pleural
      effusion, which was more significant on the right side of the thorax. The right
      lower lung lobe was consolidated, and dynamic air bronchograms were present on
      TUS. Computerised tomography of the chest was ordered. Bilateral multilobar
      consolidations were clearly appreciated with bilateral pleural effusion. Because
      of the dynamic nature of the disease process, we were able to diagnose
      pathological changes in the lung. In conclusion, TUS may be used for diagnosing
      pneumonia in the ED because it has high accuracy, low cost and no radiation
      exposure. Furthermore, it can be used bedside, and there is no need to transport
      an emergent patient to the radiology unit. 

PMID- 24672675
TI  - Computed tomography as a problem solving tool in non-radiopaque central venous
      port systems - A report of three cases.
AB  - Central venous port systems are now routinely used in oncology. The non
      functioning port system is a common issue in radiology departments. Fluoroscopy
      is a first-line imaging modality. The potential usefulness of computed tomography
      as a problem-solving tool in three complex cases with non-radiopaque central
      venous port systems is presented. 

PMID- 24672676
TI  - Violin-key shape of a common iliac artery.

PMID- 24672677
TI  - Monocytes in health and disease - Minireview.
AB  - Monocytes are important cell types of the innate immune system. Recent scientific
      evidence suggests that monocytes not only play a crucial role in our innate
      immune system by defending the host from intruding microbial pathogens but they
      also contribute to the pathogenesis and progression of diseases such as liver
      fibrosis, atherosclerosis, multiple sclerosis, and tumor metastasis. In addition,
      monocytes and monocyte-derived macrophages play a crucial beneficial role in the
      liver fibrosis regression, muscle regeneration, and the clearance of the beta
      amyloid plaques in Alzheimer's disease. Here, we summarize the origin,
      plasticity, and pathogenic potential of monocytes and monocyte-derived
      macrophages, as well as their positive role in the regression of some common
      diseases. Elucidating the comprehensive immunological role of monocytes will
      provide therapeutic advantages in either controlling disease progression or
      favoring the regression of the disease state. 

PMID- 24672679
TI  - Impact of enzymatic tissue disintegration on the level of surface molecule
      expression and immune cell function.
AB  - Immunological characterization of immune cells that reside in specific anatomic
      compartments often requires their isolation from the respective tissue on the
      basis of enzymatic tissue disintegration. Applying enzymatic digestion of primary
      splenocytes, we evaluated the impact of collagenase and dispase, two enzymes that
      are commonly used for the liberation of immune cells from tissues, on the
      detectability of 48 immunologically relevant surface molecules that are
      frequently used for flow cytometric identification, isolation, and
      characterization of immune cell subsets. Whereas collagenase treatment had only
      minor effects on surface expression of most molecules tested, dispase treatment
      considerably affected antibody-mediated detectability of the majority of surface
      markers in subsequent FACS analyses. This effect was long lasting and, in case of
      high-dose dispase treatment, evident for the majority of surface molecules even
      after 24 h of in vitro culture. Of note, high-dose dispase treatment not only
      affected surface expression of certain molecules but also impaired antigen
      specific proliferation of CD4(+) and CD8(+) T cells. Together, our data indicate
      that enzymatic tissue disintegration can have profound effects on the expression
      of a variety of cell-surface molecules with direct consequences for phenotypic
      analysis, FACS- and MACS-based target cell isolation, and immune cell function in
      cell culture experiments. 

PMID- 24672678
TI  - The complement system: history, pathways, cascade and inhibitors.
AB  - Since its discovery in the 19th century, the complement system has developed into
      a clinically significant entity. The complement system has been implicated in a
      variety of clinical conditions, from autoimmune diseases to ischemia-reperfusion
      injury in transplantation. This article charts the historical progress of our
      understanding of the complement system and provides a synopsis on the activation
      pathways and its inherent regulators. 

PMID- 24672680
TI  - Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urogenital and
      oral specimens using the cobas(r) 4800, APTIMA Combo 2(r) TMA, and ProbeTecTM ET
      SDA assays.
AB  - This prospective, multicenter clinical trial was conducted to compare the
      performance of the cobas((r)) 4800 CT/NG, APTIMA Combo 2((r)), and ProbeTec(TM)
      ET CT/GC assays for the detection of Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) in Japan. From 1274 male and female patients, more than 1900
      urine, endocervical and throat specimens were collected. Positive and negative
      concordance rates for CT and NG results obtained for urine and endocervical
      samples collected from the same patient were high in all three assays (range 96.0
      99.6%). The accuracy of the cobas((r)) 4800 CT/NG test did not differ
      significantly from that of the APTIMA Combo 2((r)) and ProbeTec(TM) ET CT/GC
      assays. The accuracy of the assays did not change depending on the order of
      collection of endocervical specimens. Concordance rates for results obtained for
      throat swabs and mouthwashes in the ProbeTec(TM) ET CT/GC and cobas((r)) 4800
      CT/NG assays, respectively, were 98.8% for CT and 95.1% for NG. These data
      suggest that the cobas((r)) 4800 CT/NG test is a reliable and highly accurate
      diagnostic tool for the detection of CT and NG in urine, genital, and oral
      specimens. Owing to the high correlation of urine and endocervical swab results
      and the ease of acquisition, urine samples are suggested as the specimen of
      choice for screening of CT and NG. 

PMID- 24672681
TI  - The current role of pulsed-field gel electrophoresis in methicillin-resistant
      Staphylococcus aureus (MRSA) typing and the retrospective identification of
      outbreaks.
AB  - The objective of this paper was to investigate whether retrospective pulsed-field
      gel electrophoresis (PFGE) of methicillin-resistant Staphylococcus aureus (MRSA)
      isolates at two-year intervals is suitable and sufficient to demonstrate changes
      in the clonal composition of MRSA isolates and to identify previously undetected
      local outbreaks. PFGE patterns of 400 MRSA isolates were collected between 2004
      and 2008 at the University of Rostock Hospital in Germany, and were used to
      assess the prevalence of MRSA clones at different time points. Only minor changes
      were detected. The combined analysis of all isolates that were collected per year
      reduced the time needed to perform this laborious procedure. The retrospective
      identification of outbreaks may require shorter intervals. Improved infection
      prevention and control measures prevented further outbreaks in previously
      affected hospital departments. In conclusion, PGFE at two-year intervals is
      sufficient to detect changes in the clonal composition of local MRSA isolates. If
      time for identification is important during outbreak investigations, more rapid
      methods with a similarly high discriminatory power such as spa typing should be
      used. 

PMID- 24672682
TI  - Differential induction of Th2- and Th1-associated responses by filarial antigens
      and endosymbiotic Wolbachia in a murine model of river blindness.
AB  - Immune responses to filarial parasites like the river blindness inducing
      Onchocerca volvulus are obscured by combined reactions to the filarial nematodes
      themselves and their endosymbiont bacteria Wolbachia. Overall, infection with
      filarial nematodes induces a strong Th2 response characterized by IL-5 production
      and to a lesser degree a Th1 response and IFNgamma production. Neutrophil and
      eosinophil infiltration into the corneal stroma are hallmark features of
      Onchocerca volvulus stimulation in a mouse model of river blindness. To determine
      the splenic and corneal response to filarial antigens in the absence of
      Wolbachia, C57BL/6 mice were immunized subcutaneously with either endosymbiotic
      Wolbachia alone, a soluble extract from the filaria Acanthocheilonema viteae that
      does not contain Wolbachia, or both, and injected into the corneal stroma.
      Neutrophil and eosinophil infiltration into the cornea was assessed by
      immunohistochemistry. In addition, Th1- and Th2-associated responses to filaria
      or Wolbachia were investigated by determining IL-5 and IFN-gamma production by
      splenocytes. We found that A. viteae in the absence of Wolbachia induced IL-5
      production and eosinophil infiltration, but not IFN-gamma. Conversely, Wolbachia
      induced IFN-gamma production and no migration of eosinophils. There was no
      difference in neutrophil infiltration. Together, these findings demonstrate a
      distinct Th-associated phenotype induced by filaria and Wolbachia. 

PMID- 24672683
TI  - Five-year retrospective epidemiological survey of anaerobic bacteraemia in a
      university hospital and rewiew of the literature.
AB  - In spite of the developments in microbiological methods, blood cultures remain
      the cornerstone for the diagnosis of bacteraemia. Classically, minimum of two
      bottles are collected on a routine basis: an aerobic bottle, allowing
      preferential growth of aerobic and facultative anaerobic microorganisms, and an
      anaerobic bottle, providing suitable environment for strict anaerobic bacteria.
      Recent reports have documented a decrease in anaerobic bacteraemias and have
      questioned the need for routine anaerobic blood cultures. Bacteraemia due to
      anaerobic organisms occurs in 0.5-12% of blood cultures worldwide; however,
      recent studies from Europe and the USA presented inconsistent data regarding the
      prevalence of anaerobic bacteraemias between 1993 and 2006. The aims of this
      retrospective survey were to determine the prevalence of bacteraemias due to
      anaerobic bacteria and evaluate the importance of anaerobic blood cultures in a
      university hospital in Szeged, Hungary. We examined the occurrence of
      bacteraemias due to anaerobic bacteria during a 5-year period, from January 2005
      to 2009, in order to identify current trends of anaerobic bacteraemias in our
      university. 

PMID- 24672684
TI  - The importance of IgM positivity in laboratory diagnosis of gestational and
      congenital syphilis.
AB  - From January 1, 2009 through December 31, 2011, from 33,753 blood samples for
      syphilis screening, Treponema pallidum infections were confirmed in 241 pregnant
      women at the Department of Dermatology, Venerology, and Dermatooncology of
      Semmelweis University Budapest. In this period, four children born to
      inadequately or untreated women were confirmed to have connatal syphilis. The
      height of rapid plasma reagin (RPR) titer was measured to determine the stage of
      the infection and to examine the success of the antilues therapy. The diagnosis
      of maternal syphilis infection was confirmed with enzyme linked immunosorbent
      assay (ELISA), T. pallidum particle agglutination (TPPA), and IgG and IgM
      immunoblots. Maternal IgM immunoblot results identify mothers at risk of
      delivering babies with connatal syphilis better than the height of maternal RPR
      titer. The standard serological tests are less useful in newborns because of IgG
      transfer across the placenta. IgM test which depends on the infant's response has
      more specificity in diagnosing connatal syphilis. 

PMID- 24672685
TI  - Cardiothoracic diseases: basic treatment.

PMID- 24672686
TI  - Pancoast tumors: characteristics and preoperative assessment.
AB  - Superior sulcus tumors (SSTs), or as otherwise known Pancoast tumors, make up a
      clinically unique and challenging subset of non-small cell carcinoma of the lung
      (NSCLC). Although the outcome of patients with this disease has traditionally
      been poor, recent developments have contributed to a significant improvement in
      prognosis of SST patients. The combination of severe and unrelenting shoulder and
      arm pain along the distribution of the eighth cervical and first and second
      thoracic nerve trunks, Horner's syndrome (ptosis, miosis, and anhidrosis) and
      atrophy of the intrinsic hand muscles comprises a clinical entity named as
      "Pancoast-Tobias syndrome". Apart NSCLC, other lesions may, although less
      frequently, result in Pancoast syndrome. In the current review we will present
      the main characteristics of the disease and focus on the preoperative assessment.

PMID- 24672687
TI  - Influence of apnoeic oxygenation in respiratory and circulatory system under
      general anaesthesia.
AB  - Apnoeic oxygenation is an alternative technique of oxygenation which is
      recommended in the consecutive oxygen administration with varying flows (2-10
      lt/min) through a catheter which is positioned over the keel of the trachea.
      Apnoeic oxygenation maintains for a significant period of time the oxygenation of
      blood in breathless conditions. This technique was first applied in 1947 by
      Draper, Whitehead, and Spencer and it was studied sporadically by other inventors
      too. However, the international literature shows few studies that have examined
      closely apnoeic oxygenation and its effects on Hemodynamic image and the
      respiratory system of the human body. Recently they have begun to arise some
      studies which deal with the application of this technique in several conditions
      such as difficult tracheal intubation, ventilation of guinea pigs in campaign
      conditions where the oxygen supply is limited and calculable, the application of
      this technique in combination with the use of extracorporeal removal of carbon
      dioxide (CO2). All the above indicate, the clinical use of this technique. 

PMID- 24672688
TI  - Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current
      literature review.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases,
      very common in general population. These obstructive airway illnesses are
      manifested with chronic inflammation affecting the whole respiratory tract.
      Obstruction is usually intermittent and reversible in asthma, but is progressive
      and irreversible in COPD. Asthma and COPD may overlap and converge, especially in
      older people [overlap syndrome-asthma-chronic obstructive pulmonary disease
      overlap syndrome (ACOS)]. Although ACOS accounts approximately 15-25% of the
      obstructive airway diseases, is not well recognised because of the structure of
      clinical trials. COPD studies exclude asthma patients and asthma studies exclude
      COPD patients, respectively. It is crucial to define asthma, COPD and overlap
      syndrome (ACOS), as notable clinical entities, which they share common pathologic
      and functional features, but they are characterized from differences in lung
      function, acute exacerbations, quality of life, hospital impact and mortality. 

PMID- 24672689
TI  - Pneumothorax and asthma.
AB  - This review is focused on the relationship between asthma, pneumothorax and
      pneumomediastinum while presenting a number of case reports that include these
      conditions. The association between pneumothorax and asthma is not widely known.
      While asthma includes a common disorder and is prevalent worldwide, its morbidity
      and mortality is high when is associated with pneumothorax. Furthermore, the
      delayed diagnosis of pneumothorax while focusing on asthma includes the higher
      risk of coincidental pneumothorax in asthmatic patients. In addition,
      pneumomediastinum is considered benign and self-limiting condition that responds
      to conservative therapy. Although it is rare, the concurrence of
      pneumomediastinum with pneumothorax may prove fatal during a serious asthma
      attack. In conclusion, the symptoms of chest pain, dyspnea or focal chest
      findings when presented in asthmatic patients, must always create suspicion of
      pneumothorax or pneumomediastinum to the physician. 

PMID- 24672690
TI  - Preoperative evaluation for lung cancer resection.
AB  - During the last decades lung cancer is the leading cause of death worldwide for
      both sexes. Even though cigarette smoking has been proved to be the main
      causative factor, many other agents (e.g., occupational exposure to asbestos or
      heavy metals, indoor exposure to radon gas radiation, particulate air pollution)
      have been associated with its development. Recently screening programs proved to
      reduce mortality among heavy-smokers although establishment of such strategies in
      everyday clinical practice is much more difficult and unknown if it is cost
      effective compared to other neoplasms (e.g., breast or prostate cancer). Adding
      severe comorbidities (coronary heart disease, COPD) to the above reasons as
      cigarette smoking is a common causative factor, we could explain the low surgical
      resection rates (approximately 20-30%) for lung cancer patients. Three clinical
      guidelines reports of different associations have been published (American
      College of Chest Physisians, British Thoracic Society and European Respiratory
      Society/European Society of Thoracic Surgery) providing detailed algorithms for
      preoperative assessment. In the current mini review, we will comment on the
      preoperative evaluation of lung cancer patients. 

PMID- 24672691
TI  - Airway inflammation in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease
      whose incidence and mortality increases every year. It is associated with an
      abnormal inflammatory response of the lung to toxic particles or gases (usually
      cigarette smoke). A central role in the pathophysiology has been shown to play a
      chronic inflammation of the airways that is expressed primarily by hypersecretion
      of mucus, stenosis of the smaller airways and the establishment of pulmonary
      emphysema. There is an increasing trend for assessing the inflammatory pattern of
      inflammatory airway diseases through mediators measured by noninvasive
      techniques. Markers in biological fluids and exhaled air have been the subject of
      intense evaluation over the past few years, with some of them reaching their
      introduction into clinical practice, while others remain as research tools. Of
      particular interest for the scientific community is the discovery of clinically
      exploitable biomarkers associated with specific phenotypes of the disease.
      Studying the effects of therapeutic interventions in these biomarkers may lead to
      targeted therapy based on phenotype and this is perhaps the future of
      therapeutics in COPD. 

PMID- 24672692
TI  - Surgical management of cardiac implantable electronic device infections.
AB  - PURPOSE: The infection of cardiac implantable electronic devices (CIED) is a
      serious and potentially lethal complication. The population at risk is growing,
      as the device implantation is increasing especially in older patients with
      associated comorbid conditions. Our purpose was to present the management of this
      complicated surgical condition and to extract the relevant conclusions. METHODS:
      During a 3-year period 1,508 CIED were implanted in our hospital. We treated six
      cases of permanent pacemaker infection with localized pocket infection or
      endocarditis. In accordance to the recent AHA/ACC guidelines, complete device
      removal was decided in all cases. The devices were removed under general
      anaesthesia, with a midline sternotomy, under extracorporeal circulation on the
      beating heart. Epicardial permanent pacing electrodes were placed on the right
      atrium and ventricle before the end of the procedure. RESULTS: The postoperative
      course of all patients was uncomplicated and after a follow up period of five
      years no relapse of infection occurred. CONCLUSIONS: Management protocols that
      include complete device removal are the only effective measure for the
      eradication of CIED infections. Although newer technologies have emerged and
      specialized techniques of percutaneous device removal have been developed, the
      surgical alternative to these methods can be a safe solution in cases of infected
      devices.

PMID- 24672694
TI  - Epithelial-myoepithelial carcinoma of the trachea-a rare entity case report.
AB  - Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological
      behavior and clinical course still remain to be defined. Epithelial-myoepithelial
      carcinoma (EMCa) is a low-grade malignant tumour. According to literature, most
      commonly occurs in salivary glands, particularly in parotic gland, but it can
      also occur in unusual locations such as breast, lachrymal gland, nose, paranasal
      sinus, lung, bronchus and, as in our case, trachea. There are no many documented
      case reports of a primary myoepithelial carcinoma in the trachea. We report a
      case of a 34-year-old man diagnosed with this unusual location of an epithelial
      myoepithelial tumor. The tumour was removed by segmental tracheal resection and
      end-to-end anastomosis. 

PMID- 24672693
TI  - Therapeutic modalities for Pancoast tumors.
AB  - A Pancoast tumor, also called a pulmonary sulcus tumor or superior sulcus tumor,
      is a tumor of the pulmonary apex. It is a type of lung cancer defined primarily
      by its location situated at the top end of either the right or left lung. It
      typically spreads to nearby tissues such as the ribs and vertebrae. Most Pancoast
      tumors are non-small cell cancers. The growing tumor can cause compression of a
      brachiocephalic vein, subclavian artery, phrenic nerve, recurrent laryngeal
      nerve, vagus nerve, or, characteristically, compression of a sympathetic ganglion
      resulting in a range of symptoms known as Horner's syndrome. Pancoast tumors are
      named for Henry Pancoast, a US radiologist, who described them in 1924 and
      1932.The treatment of a Pancoast lung cancer may differ from that of other types
      of non-small cell lung cancer (NSCLC). Its position and close proximity to vital
      structures may make surgery difficult. As a result, and depending on the stage of
      the cancer, treatment may involve radiation and chemotherapy given prior to
      surgery. Surgery may consist of the removal of the upper lobe of a lung together
      with its associated structures as well as mediastinal lymphadenectomy. Surgical
      access may be via thoracotomy from the back or the front of the chest and
      modification. Careful patient selection, improvements in imaging such as the role
      of PET-CT in restaging of tumors, radiotherapy and surgical advances, the
      management of previously inoperable lesions by a combined experienced thoracic
      neurosurgical team and prompt recognition and therapy of postoperative
      complications has greatly increased local control and overall survival for
      patients with these tumors. 

PMID- 24672695
TI  - Current options for treatment of chronic coronary artery disease.
AB  - The primary issues must be discussed regarding the decision making of treating a
      patient with chronic coronary artery disease (CAD), are the appropriateness of
      revascularization and the method which will be applied. The criteria will be the
      symptoms, the evidence of ischemia and the anatomical complexity of the coronary
      bed. Main indications are persistence of symptoms, despite oral medical treatment
      and the prognosis of any intervention. The prognosis is based on left ventricular
      function, on the number of coronary arteries with significant stenosis and the
      ischemic burden. For patients with symptoms and no evidence of ischemia, there is
      no benefit from revascularization. If ischemia is proven, revascularization is
      beneficial. If revascularization is decided, the next important issue must be
      taken under consideration is the choice of the appropriate method to be applied,
      surgical or interventional approach. Current treatment options will be presented.

PMID- 24672696
TI  - Early reoperation performed for the management of complications in patients
      undergoing general thoracic surgical procedures.
AB  - OBJECTIVE: To detect the rate and predisposing factors for the development of
      postoperative complications requiring re-operation for their control in the
      immediate postoperative period. METHODS: During the time period 2009-2012, 719
      patients (male: 71.62%, mean age: 54+/-19 years) who underwent a wide range of
      general thoracic surgery procedures, were retrospectively collected. Data of
      patients who underwent early re-operation for the management of postoperative
      complications were assessed for identification of the responsible causative
      factors. RESULTS: Overall, 33/719 patients (4.6%) underwent early re-operation to
      control postoperative complications. Early re-operation was obviated by the need
      to control bleeding or to drain clotted hemothoraces in nine cases (27.3%), to
      manage a prolonged air leak in six cases (18.2%), to drain a post-thoracotomy
      empyema in five cases (15.2%), to revise the thoracotomy incision or an ischemic
      musculocutaneous flap in five cases (15.2%), to manage a bronchopleural fistula
      in four cases (12.1%), to manage persistent atelectasis of the remaining lung in
      two cases (6.1%), to cease a chyle leak in one case (3%) and to plicate the right
      hemidiaphragm in another one case (3%). The factors responsible for the
      development of complications requiring reopening of the chest for their
      management were technical in 17 cases (51.5%), initial surgery for lung or
      pleural infections in 9 (27.3%), the recent antiplatelet drug administration in 4
      (12.1%) and advanced lung emphysema in 3 (9.1%). Mortality of re-operations was
      6.1% (2/33) and it was associated with the need to proceed with completion
      pneumonectomy in the two cases with persistent atelectasis of the remaining lung
      and permanent parenchymal damage. The majority of complications requiring
      reoperation were observed after lung parenchyma resection (17 out of the 228
      procedures/7.4%) or pleurectomy (7 out of the 106 procedures/6.5%). Reoperations
      after video-assisted thoracic surgery (VATS) were uncommon (2 out of the 99
      procedures/2%). CONCLUSIONS: The rate of complications requiring reoperation
      after general thoracic surgery procedures is low and it is mainly related to
      technical issues from the initial surgery, the recent administration of
      antiplatelet drugs, the presence of advanced emphysema and surgery for infectious
      diseases. The need to proceed with completion pneumonectomy has serious risk for
      fatal outcome.

PMID- 24672697
TI  - Thirteen years follow-up of heart myxoma operated patients: what is the
      appropriate surgical technique?
AB  - BACKGROUND: Cardiac myxoma is a benign neoplasm that represents the most
      prevalent primary tumor of the heart. If not treated with the right surgical
      technique recurrence occurs. Aim of our study is to present our surgical approach
      and the histology of the tumors resected. METHODS: All patients, except for one,
      underwent extracorporeal circulation and mild hypothermia, right atrial or both
      atrial incision and excision of the fossa ovalis, followed by prosthetic patch
      suturing. All specimens were submitted for microscopic evaluation (haematoxylin
      eosin). We contacted personally each patient and asked them to complete a
      standardized questionnaire, concerning their peri-operative characteristics.
      RESULTS: Six cases were "active" myxomas, 3 were "mildly active" and 3 were
      "inactive". "Normal differentiation" was seen in 6, "medium" in 1 and "poor" in 5
      cases. In our series there were no recurrences recorded during the follow-up
      period. CONCLUSIONS: The ideal approach, according to our experience is right
      atrial or both atrial incision as described by Shumacker and King, with excision
      of the fossa ovalis and the surrounding tissues and closure with a pericardial
      patch. Such a technique provides an excellent long-term survival in these
      patients.

PMID- 24672698
TI  - Review of mitral valve insufficiency: repair or replacement.
AB  - Mitral valve (MV) dysfunction is the second-most common clinically significant
      form of valvular defect in adults. MV regurgitation occurs with the increasing
      frequency of degenerative changes of the aging process. Moreover, other causes of
      clinically significant MV regurgitation include cardiac ischemia, infective
      endocarditis and rhematic disease more frequently in less developed countries.
      Recent evidence suggests that the best outcomes after repair of severe
      degenerative mitral regurgitation (MR) are achieved in asymptomatic or minimally
      symptomatic patients, who are selected for surgery soon after diagnosis on the
      basis of echocardiography. This review will focus on the surgical management of
      mitral insufficiency according to its aetiology today and will give insight to
      some of the perspectives that lay in the future. 

PMID- 24672699
TI  - Right heart failure post left ventricular assist device implantation.
AB  - Right heart failure (RHF) is a frequent complication following left ventricular
      assist device (LVAD) implantation. The incidence of RHF complicates 20-50%
      (range, 9-44%) of cases and is a major factor of postoperative morbidity and
      mortality. Unfortunately, despite the fact that many risk factors contributing to
      the development of RHF after LVAD implantation have been identified, it seems to
      be extremely difficult to avoid them. Prevention of RHF consists of the
      management of the preload and the afterload of the right ventricle with optimum
      inotropic support. The administration of vasodilators designed to reduce
      pulmonary vascular resistance is standard practice in most centers. The surgical
      attempt of implantation of a right ventricular assist device does not always
      resolve the problem and is not available in all cardiac surgery centers. 

PMID- 24672700
TI  - Cerebral oximetry in cardiac anesthesia.
AB  - Cerebral oximetry based on near-infrared spectroscopy (NIRS) is increasingly used
      during the perioperative period of cardiovascular operations. It is a noninvasive
      technology that can monitor the regional oxygen saturation of the frontal cortex.
      Current literature indicates that it can stratify patients preoperatively
      according their risk. Intraoperatively, it provides continuous information about
      brain oxygenation and allows the use of brain as sentinel organ indexing overall
      organ perfusion and injury. This review focuses on the clinical validity and
      applicability of this monitor for cardiac surgical patients. 

PMID- 24672701
TI  - Effect of lornoxicam in lung inflammatory response syndrome after operations for
      cardiac surgery with cardiopulmonary bypass.
AB  - BACKGROUND: The establishment of Extracorporeal Circulation (EC) significantly
      contributed to improvement of cardiac surgery, but this is accompanied by harmful
      side-effects. The most important of them is systemic inflammatory response
      syndrome. Many efforts have been undertaken to minimize this problem but
      unfortunately without satisfied solution to date. MATERIALS AND METHODS:
      Lornoxicam is a non steroid anti-inflammatory drug which temporally inhibits the
      cycloxygenase. In this clinical trial we study the effect of lornoxicam in lung
      inflammatory response after operations for cardiac surgery with cardiopulmonary
      bypass. In our study we conclude 14 volunteers patients with ischemic coronary
      disease undergoing coronary artery bypass grafting with EC. In seven of them 16
      mg lornoxicam was administered iv before the anesthesia induction and before the
      connection in heart-lung machine. In control group (7 patients) we administered
      the same amount of normal saline. RESULTS: Both groups are equal regarding pro
      operative and intra-operative parameters. The inflammatory markers were
      calculated by Elisa method. We measured the levels of cytokines (IL-6, IL-8, TNF
      a), adhesion molecules (ICAM-1, e-Selectin, p-Selectin) and matrix
      metaloproteinase-3 (MMP-3) just after anesthesia induction, before and after
      cardiopulmonary bypass, just after the patients administration in ICU and after 8
      and 24 hrs. In all patients we estimated the lung's inflammatory reaction with
      lung biopsy taken at the begging and at the end of the operation. We calculated
      hemodynamics parameters: Cardiac Index (CI), Systemic Vascular Resistance Index
      (SVRI), Pulmonary Vascular Resistance Index (PVRI), Left Ventricular Stroke Work
      Index (LVSWI), Right Ventricular Stroke Work Index (RVSWI), and the Pulmonary
      arterial pressure, and respiratory parameters too: alveolo-arterial oxygen
      difference D (A-a), intrapulmonary shunt (Qs/Qt) and pulmonary Compliance. IL-6
      levels of lornoxicam group were statistical significant lower at 1st
      postoperative day compared to them of control group (113+/-49 and 177+/-20
      respectively, P=0.008). ICAM-1 levels were statistical significant lower at the
      patient admission in ICU, compared to them of control group (177+/-29 and 217+/
      22 respectively, P=0.014), and the 1st postoperative day compared to them in
      control group (281+/-134 and 489+/-206 respectively, P=0.045). P-selectin levels
      were statistical significant lower, compared to them in control group in four
      measurements (97+/-23 and 119+/-7 respectively, P=0.030, 77+/-19 and 101+/-20
      respectively, P=0.044, 86+/-4 and 105+/-13 respectively, P=0.06, 116+/-13 and
      158+/-17 respectively, P=0.000). CONCLUSIONS: Hemodynamics and respiratory
      parameters were improved compared to control group, but these differences was not
      statistical significant. Eosinofil adhesion and sequestration in intermediate
      tissue of lung parenchyma were significantly lower compared to control group.
      Also, alveolar edema was not noted in lornoxicam's group. Lornoxicam reduce the
      inflammatory response in patients undergone coronary artery bypass grafting with
      extracorporeal circulation. This calculated from levels reduction of IL-6, ICAM-1
      kappaalphaiota p-Selectin, and from lung pathologoanatomic examination (absence
      of alveolar edema, reduce in eosinofil adhesion and sequestration in intermediate
      tissues). Despite the favorable effect of lornoxicam on the hemodinamics and
      respiratory parameters these improvement did not seem to be statistical
      significant.

PMID- 24672702
TI  - Left atrial appendage exclusion-Where do we stand?
AB  - Atrial fibrillation (AF) is consider to be the most common cardiac arrhythmia
      with an increasingly prevalence. It is postulated that the source of
      thromboembolism in 90% of patients with non-valvular AF arises from the left
      atrial appendage (LAA). Stroke is the most feared and life threatening
      consequence of thromboembolism. Oral anticoagulation (OAC) with vitamin-K
      antagonists is the standard medical therapy for stroke prevention in patients
      with AF. Unfortunately, chronic therapy with vitamin-K-antagonists is
      contraindicated in 14% to 44% of patients with AF who are at risk for stroke, and
      its benefits are limited by underutilization, narrow therapeutic window and
      increased risk for bleeding, making it often undesired. Therefore, mechanical LAA
      exclusion is a means of preventing thrombus formation in the appendage and
      subsequent thromboembolic events in these patients. The LAA can be excluded from
      the systemic circulation via surgical, percutaneous, or thoracoscopic approaches.
      Several studies of percutaneous transcatheter delivery of dedicated LAA exclusion
      devices, such as the percutaneous left atrial appendage transcatheter occlusion
      (PLAATO) device, Watchman device and the Amplatzer cardiac plug, have shown
      encouraging results as an alternative to vitamin-K-antagonists therapy for
      selected patients, good feasibility and efficacy, with a high rate of successful
      implantation. We discuss the current evidence for LAA exclusion in patients and
      review their results. 

PMID- 24672704
TI  - Pneumothorax after transthoracic needle biopsy of lung lesions under CT guidance.
AB  - Transthoracic needle biopsy (TTNB) is done with imaging guidance and most
      frequently by a radiologist, for the aim is to diagnose a defined mass. It is
      integral in the diagnosis and treatment of many thoracic diseases, and is an
      important alternative to more invasive surgical procedures. FNAC is a method of
      aspiration cytopathology, which with transthoracic biopsy ("core biopsy") is a
      group of percutaneous minimally invasive diagnostic procedures for exploration of
      lung lesions. Needle choice depends mostly upon lesion characteristics and
      location. A recent innovation in biopsy needles has been the introduction of
      automatic core biopsy needle devices that yield large specimens and improve the
      diagnostic accuracy of needle biopsy. Both computed tomography and ultrasound may
      be used as imaging guidance for TTNB, with CT being more commonly utilized.
      Common complications of TTNB include pneumothorax and hemoptysis. The incidence
      of pneumothorax in patients undergoing TTNB has been reported to be from 9-54%,
      according to reports published in the past ten years, with an average of around
      20%. Which factors statistically correlate with the frequency of pneumothorax
      remain controversial, but most reports have suggested that lesion size, depth and
      the presence of emphysema are the main factors influencing the incidence of
      pneumothorax after CT-guided needle biopsy. On the contrary, gender, age, and the
      number of pleural passes have not been shown to correlate with the incidence of
      pneumothorax. The problem most responsible for complicating outpatient
      management, after needle biopsy was performed, is not the presence of the
      pneumothorax per se, but an increase in the size of the pneumothorax that
      requires chest tube placement and patient hospitalization. Although it is a
      widely accepted procedure with relatively few complications, precise planning and
      detailed knowledge of various aspects of the biopsy procedure is mandatory to
      avert complications. 

PMID- 24672706
TI  - Silicone Oil Reinjection without Macular Buckling for Treatment of Recurrent
      Myopic Macular Hole Retinal Detachment after Silicone Oil Removal.
AB  - Purpose. To evaluate the efficacy of silicone oil (S.O) reinjection without
      macular buckling for treatment of recurrent myopic macular hole retinal
      detachment (MHRD) after silicone oil removal. Methods. A retrospective
      consecutive interventional study from medical reports on cases of myopic MHRD.
      Fifty-three eyes of 51 patients underwent silicone oil removal after successful
      repair of MHRD were reviewed. The main outcomes were the retinal status after
      silicone oil removal and management of recurrent cases. Results. The rate of
      recurrent RD (Re RD) after silicone oil removal was 11.3% (6 out of 53 eyes). One
      case refused any other interference. In the remaining 5 eyes, 4 eyes (80%) could
      be reattached by S.O re-injection and one eye (20%) developed Re RD after S.O re
      injection. Range of followup after management of recurrence was 5-53 months (mean
      18.7 months). Conclusions. This case series concluded that the risk factors for
      recurrent RD after silicone oil removal from cases of myopic MHRD were high
      myopia, open flat MH, and large posterior staphyloma. Revision of vitrectomy and
      S.O re-injection can reattach most of recurrent cases. 

PMID- 24672705
TI  - The First Fifty ABO Blood Group Incompatible Kidney Transplantations: The
      Rotterdam Experience.
AB  - This study describes the single center experience and long-term results of ABOi
      kidney transplantation using a pretransplantation protocol involving
      immunoadsorption combined with rituximab, intravenous immunoglobulins, and triple
      immune suppression. Fifty patients received an ABOi kidney transplant in the
      period from 2006 to 2012 with a follow-up of at least one year. Eleven antibody
      mediated rejections were noted of which 5 were mixed antibody and cellular
      mediated rejections. Nine cellular mediated rejections were recorded. Two grafts
      were lost due to rejection in the first year. One-year graft survival of the ABOi
      grafts was comparable to 100 matched ABO compatible renal grafts, 96% versus 99%.
      At 5-year follow-up, the graft survival was 90% in the ABOi versus 97% in the
      control group. Posttransplantation immunoadsorption was not an essential part of
      the protocol and no association was found between antibody titers and subsequent
      graft rejection. Steroids could be withdrawn safely 3 months after
      transplantation. Adverse events specifically related to the ABOi protocol were
      not observed. The currently used ABOi protocol shows good short and midterm
      results despite a high rate of antibody mediated rejections in the first years
      after the start of the program. 

PMID- 24672703
TI  - Lung inflammatory response syndrome after cardiac-operations and treatment of
      lornoxicam.
AB  - The majority of patients survive after extracorporeal circulation without any
      clinically apparent deleterious effects. However, disturbances exist in various
      degrees sometimes, which indicate the harmful effects of cardiopulmonary bypass
      (CPB) in the body. Several factors during extracorporeal circulation either
      mechanical dependent (exposure of blood to non-biological area) or mechanical
      independent (surgical wounds, ischemia and reperfusion, alteration in body
      temperature, release of endotoxins) have been shown to trigger the inflammatory
      reaction of the body. The complement activation, the release of cytokines, the
      leukocyte activation and accumulation as well as the production of several
      "mediators" such as oxygen free radicals, metabolites of arachidonic acid,
      platelet activating factors (PAF), nitric acid, and endothelin. The investigation
      continues today on the three metabolites of lornoxicam (the hydroxylated
      metabolite and two other metabolites of unknown chemical composition) to search
      for potential new pharmacological properties and activities. 

PMID- 24672707
TI  - Current treatment limitations in age-related macular degeneration and future
      approaches based on cell therapy and tissue engineering.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      Western world. With an ageing population, it is anticipated that the number of
      AMD cases will increase dramatically, making a solution to this debilitating
      disease an urgent requirement for the socioeconomic future of the European Union
      and worldwide. The present paper reviews the limitations of the current therapies
      as well as the socioeconomic impact of the AMD. There is currently no cure
      available for AMD, and even palliative treatments are rare. Treatment options
      show several side effects, are of high cost, and only treat the consequence, not
      the cause of the pathology. For that reason, many options involving cell therapy
      mainly based on retinal and iris pigment epithelium cells as well as stem cells
      are being tested. Moreover, tissue engineering strategies to design and
      manufacture scaffolds to mimic Bruch's membrane are very diverse and under
      investigation. Both alternative therapies are aimed to prevent and/or cure AMD
      and are reviewed herein. 

PMID- 24672709
TI  - Evaluation and treatment of perioperative corneal abrasions.
AB  - Purpose. To evaluate perioperative risk factors for corneal abrasion (CA) and to
      determine current care for perioperative CA in a tertiary care setting. Methods.
      Hospital-based, cross-sectional study. In Operating Room and Post-Anesthesia Care
      Units patients, a comparison of cases and controls was evaluated to elucidate
      risk factors, time to treatment, and most common treatments prescribed for
      corneal abrasions. Results. 86 cases of corneal abrasion and 89 controls were
      identified from the 78,542 surgical procedures performed over 2 years.
      Statistically significant risk factors were age (P = 0.0037), general anesthesia
      (P < 0.001), greater average estimated blood loss (P < 0.001), eyes taped during
      surgery (P < 0.001), prone position (P < 0.001), trendelenburg position (P <
      0.001), and supplemental oxygen en route to and in the Post-Anesthesia Care Units
      (P < 0.001). Average time to complaint was 129 minutes. 94% of cases had an
      inpatient ophthalmology consult, with an average time to consult of 164 minutes.
      The most common treatment was artificial tears alone (40%), followed by
      combination treatment of antibiotic ointment and artificial tears (35.3%).
      Conclusions. Trendelenburg positioning is a novel risk factor for CA. Diagnosis
      and treatment of perioperative corneal abrasions by an ophthalmologist typically
      require three hours in the tertiary care setting. 

PMID- 24672710
TI  - F6H8 as an Intraoperative Tool and F6H8/Silicone Oil as a Postoperative Tamponade
      in Inferior Retinal Detachment with Inferior PVR.
AB  - Purpose. To evaluate the effectiveness and safety of perfluorohexyloctane (F6H8)
      for intraoperative flattening of the retina and of F6H8/silicone oil (SO) 1000
      cSt as a postoperative tamponade for inferior retinal detachment with inferior
      proliferative vitreoretinopathy. Methods. This is a retrospective review of 22
      patients who underwent pars plana vitrectomy using F6H8 as an intraoperative tool
      to flatten the retina. At the end of the surgery a direct partial exchange
      between F6H8 and SO 1000 cSt was performed, tamponing the eye with different
      ratios of F6H8/SO (70/30, 60/40, 50/50, 40/30, and 30/70). Anatomical and
      functional results and complications were evaluated over the follow-up period
      (mean 22.63 months). Results. F6H8 was efficacious for intraoperative flattening
      of the retina. Twenty-one of the 22 patients achieved a complete retinal
      reattachment. Postoperative visual acuity (VA) ranged from light perception to
      20/70, with 72% of patients obtaining VA better than 20/400. No
      emulsification/inflammation was observed whatever the ratio of F6H8/SO used. With
      higher ratios of F6H8/SO (70/30 and 60/40) cloudiness of the tamponade was
      observed. A transparent mixture was present with all the other ratios.
      Conclusions. The surgical technique adopted is very simple and safe. The optimal
      F6H8/SO ratio seems to be between 50/50 and 30/70. 

PMID- 24672708
TI  - Do nutritional supplements have a role in age macular degeneration prevention?
AB  - Purpose. To review the proposed pathogenic mechanisms of age macular degeneration
      (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids ( omega 
      3) supplements in AMD prevention. Materials and Methods. Current knowledge on the
      cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies
      on the effects of AOX and omega -3 were addressed all together with the
      scientific evidence and the personal opinion of professionals involved in the
      Retina Group of the OFTARED (Spain). Results. High dietary intakes of omega -3
      and macular pigments lutein/zeaxanthin are associated with lower risk of
      prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed
      a beneficial effect of high doses of vitamins C, E, beta-carotene, and
      zinc/copper in reducing the rate of progression to advanced AMD in patients with
      intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that
      lutein and zeaxanthin may substitute beta-carotene because of its potential
      relationship with increased lung cancer incidence. Conclusion. Research has
      proved that elder people with poor diets, especially with low AOX and omega -3
      micronutrients intake and subsequently having low plasmatic levels, are more
      prone to developing AMD. Micronutrient supplementation enhances antioxidant
      defense and healthy eyes and might prevent/retard/modify AMD. 

PMID- 24672711
TI  - Clinical significance of optic disc progression by topographic change analysis
      maps in glaucoma: an 8-year follow-up study.
AB  - Aim. To investigate the ability of Heidelberg Retina Tomograph (HRT3) Topographic
      Change Analysis (TCA) map to predict the subsequent development of clinical
      change, in patients with glaucoma. Materials. 61 eyes of 61 patients, which, from
      a retrospective review were defined as stable on optic nerve head (ONH)
      stereophotographs and visual field (VF), were enrolled in a prospective study.
      Eyes were classified as TCA-stable or TCA-progressed based on the TCA map. All
      patients underwent HRT3, VF, and ONH stereophotography at 9-12 months intervals.
      Clinical glaucoma progression was determined by masked assessment of ONH
      stereophotographs and VF Guided Progression Analysis. Results. The median (IQR)
      total HRT follow-up period was 8.1 (7.3, 9.1) years, which included a median
      retrospective and prospective follow-up time of 3.9 (3.1, 5.0) and 4.0 (3.5, 4.7)
      years, respectively. In the TCA-stable eyes, VF and/or photographic progression
      occurred in 5/13 (38.4%) eyes compared to 11/48 (22.9%) of the TCA-progressed
      eyes. There was no statistically significant association between TCA progression
      and clinically relevant (photographic and/or VF) progression (hazard ratio, 1.18;
      P = 0.762). The observed median time to clinical progression from enrollment was
      significantly shorter in the TCA-progressed group compared to the TCA-stable
      group (P = 0.04). Conclusion. Our results indicate that the commercially
      available TCA progression criteria do not adequately predict subsequent
      photographic and/or VF progression. 

PMID- 24672712
TI  - Beta-Blockers in the Management of Hypertension and/or Chronic Kidney Disease.
AB  - This minireview provides current summaries of beta-blocker use in the management
      of hypertension and/or chronic kidney disease. Accumulated evidence suggests that
      atenolol is not sufficiently effective as a primary tool to treat hypertension.
      The less-than-adequate effect of beta-blockers in lowering the blood pressure and
      on vascular protection, and the unfavorable effects of these drugs, as compared
      to other antihypertensive agents, on the metabolic profile have been pointed out.
      On the other hand, in patients with chronic kidney disease, renin-angiotensin
      system blockers are the drugs of first choice for achieving the goal of renal
      protection. Recent studies have reported that vasodilatory beta-blockers have
      adequate antihypertensive efficacy and less harmful effects on the metabolic
      profile, and also exert beneficial effects on endothelial function and renal
      protection. However, there is still not sufficient evidence on the beneficial
      effects of the new beta-blockers. 

PMID- 24672713
TI  - The impact of mood and anxiety disorders on incident hypertension at one year.
AB  - Background. Studies assessing the association between psychological factors and
      hypertension have been equivocal, which may reflect limitations in the assessment
      of psychological factors. Purpose. To assess the relationship between mood and
      anxiety disorders, measured using a psychiatric interview, and 1-year incident
      hypertension. Methods. 197 nonhypertensive individuals undergoing exercise stress
      testing at baseline provided follow-up data at 1 year. Baseline assessments
      included a structure psychiatric interview (PRIME-MD), physician diagnosis of
      hypertension, and measured blood pressure. At follow-up, hypertension status was
      assessed via self-reported physician diagnosis. Results. Having an anxiety
      disorder was associated with a 4-fold increase in the risk of developing
      hypertension (adjusted OR = 4.14, 95% CIs = 1.18-14.56). In contrast, having a
      mood disorder was not associated with incident hypertension (adjusted OR = 1.21,
      95% CIs = 0.24-5.86). Conclusions. There are potential mechanisms which could
      explain our differential mood and anxiety findings. The impact of screening and
      treatment of anxiety disorders on hypertension needs to be explored. 

PMID- 24672714
TI  - Trajectories of objectively measured physical activity among secondary students
      in Canada in the context of a province-wide physical education policy: a
      longitudinal analysis.
AB  - Lower levels of physical activity are associated with childhood obesity. School
      physical education (PE) policies have been identified as critical to improve
      child and adolescent physical activity levels but there has been little
      evaluation of such policies. In the province of Manitoba, Canada, the government
      implemented a mandatory PE policy in secondary schools designed to increase the
      daily physical activity levels of adolescents. The objective of this study was to
      examine the longitudinal changes in and the factors associated with the physical
      activity trajectories of adolescents in Manitoba during their tenure as secondary
      school students in the context of this school PE policy. The results found,
      despite the PE policy, a grade-related decline in the physical activity
      trajectories of adolescents; however, the decline in physical activity was
      attenuated among adolescents with low and moderate baseline physical activity
      compared to adolescents with high baseline physical activity and among
      adolescents who attended schools in neighbourhoods of low compared to high
      socioeconomic status. There are several possible explanations for these findings,
      including the influence of the PE policy on the PA patterns of adolescent
      subpopulations that tend to be at higher risk for inactivity in both childhood
      and adult life. 

PMID- 24672715
TI  - Validation of the friedewald formula in patients with metabolic syndrome.
AB  - Currently, the Friedewald formula (FF) is the main method for evaluating low
      density lipoprotein cholesterol (LDL-c). Recently, many limitations have emerged
      regarding its use, including patients with triglyceride levels >=400 mg/dL,
      diabetes mellitus, and kidney or hepatic chronic diseases. We analyzed the use of
      the FF in patients with metabolic syndrome. We selected patients with known
      metabolic syndrome that fulfilled the National Cholesterol Education Program
      Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in
      Adults (Adult Treatment Panel III) Final Report and excluded patients with
      triglyceride levels >=400 mg/dL and chronic liver and/or kidney disease. Using
      direct assays, we measured total cholesterol, high-density lipoprotein
      cholesterol, triglycerides, and LDL-c. Then, LDL-c was estimated using the FF and
      compared with the LDL-c by direct assay. The sample size was 135 patients. Using
      the FF, the mean LDL-c value was 124.4 +/- 42.1 mg/dL; it was 125.1 +/- 38.5
      mg/dL by direct assay. The correlation coefficient between these two methods was
      0.89, with statistical significance (P  value < 0.001). There were no significant
      differences between the patients with triglyceride levels >150 mg/dL (P = 0.618).
      In conclusion, FF is a good method for estimating LDL-c in patients with
      metabolic syndrome. 

PMID- 24672716
TI  - The Influence of an Obesogenic Diet on Oxysterol Metabolism in C57BL/6J Mice.
AB  - Our current understanding of oxysterol metabolism during different disease states
      such as obesity and dyslipidemia is limited. Therefore, the aim of this study was
      to determine the effect of diet-induced obesity on the tissue distribution of
      various oxysterols and the mRNA expression of key enzymes involved in oxysterol
      metabolism. To induce obesity, male C57BL/6J mice were fed a high fat-cholesterol
      diet for 24 weeks. Following diet-induced obesity, plasma levels of 4 beta 
      hydroxycholesterol, 5,6 alpha -epoxycholesterol, 5,6 beta -epoxycholesterol, 7
      alpha -hydroxycholesterol, 7 beta -hydroxycholesterol, and 27-hydroxycholesterol
      were significantly (P < 0.05) increased. In the liver and adipose tissue of the
      obese mice, 4 beta -hydroxycholesterol was significantly (P < 0.05) increased,
      whereas 27-hydroxycholesterol was increased only in the adipose tissue. No
      significant changes in either hepatic or adipose tissue mRNA expression were
      observed for oxysterol synthesizing enzymes 4 beta -hydroxylase, 27-hydroxylase,
      or 7 alpha -hydroxylase. Hepatic mRNA expression of SULT2B1b, a key enzyme
      involved in oxysterol detoxification, was significantly (P < 0.05) elevated in
      the obese mice. Interestingly, the appearance of the large HDL1 lipoprotein was
      observed with increased oxysterol synthesis during obesity. In diet-induced obese
      mice, dietary intake and endogenous enzymatic synthesis of oxysterols could not
      account for the increased oxysterol levels, suggesting that nonenzymatic
      cholesterol oxidation pathways may be responsible for the changes in oxysterol
      metabolism. 

PMID- 24672717
TI  - Simple measures of function and symptoms in hospitalized heart failure patients
      predict short-term cardiac event-free survival.
AB  - Background. Heart failure (HF) is a prevalent chronic condition where patients
      experience numerous uncomfortable symptoms, low functional status, and high
      mortality rates. Objective. To determine whether function and/or symptoms predict
      cardiac event-free survival in hospitalized HF patients within 90 days of
      hospital discharge. Methods. Inpatients (N = 32) had HF symptoms assessed with 4
      yes/no questions. Function was determined with NYHA Classification, Katz Index of
      Activities of Daily Living (ADLs), and directly with the short physical
      performance battery (SPPB). Survival was analyzed with time to the first
      postdischarge cardiac event with events defined as cardiac rehospitalization,
      heart transplantation, or death. Results. Mean age was 58.2 +/- 13.6 years.
      Patient reported ADL function was nearly independent (5.6 +/- 1.1) while direct
      measure (SPPB) showed moderate functional limitation (6.4 +/- 3.1). Within 90
      days, 40.6% patients had a cardiac event. At discharge, each increase in NYHA
      Classification was associated with a 3.4-fold higher risk of cardiac events (95%
      CI 1.4-8.5). Patients reporting symptoms of dyspnea, fatigue, and orthopnea
      before discharge had a 4.0-fold, 9.7-fold, and 12.8-fold, respectively, greater
      risk of cardiac events (95% CI 1.2-13.2; 1.2-75.1; 1.7-99.7). Conclusions. Simple
      assessments of function and symptoms easily performed at discharge may predict
      short-term cardiac outcomes in hospitalized HF patients. 

PMID- 24672718
TI  - Minimally invasive local treatments for bone and pulmonary metastases.
AB  - Surgery and chemotherapy have historically been the mainstay of treatment in
      patients with metastatic disease. However there are many alternative therapies
      available to relieve the symptoms and morbidity of metastases. In this paper, we
      review the role and highlight the advantages of minimally invasive techniques
      employed in patients with pulmonary and bone metastases. 

PMID- 24672719
TI  - Elevated heparin-induced antibodies are more common in diabetic patients with
      vascular disease.
AB  - Background. Hypercoagulable disorders can lead to deep vein thrombosis (DVT),
      arterial thrombosis or embolization, and early or recurrent bypass graft failure.
      The purpose of this study was to identify whether diabetes increased the
      likelihood of heparin-induced platelet factor 4 antibodies in at risk vascular
      patients. Methods. We reviewed clinical data on 300 consecutive patients. A
      hypercoagulable workup was performed if patients presented with (1) early
      bypass/graft thrombosis (<30 days), (2) multiple bypass/graft thrombosis, and (3)
      a history of DVT, pulmonary embolus (PE), or native vessel thrombosis. Relevant
      clinical variables were analyzed and compared between patients with diabetes (DM)
      and without diabetes (nDM). Results. 85 patients (47 women; age 53 +/- 16 years,
      range 16-82 years) had one of the defined conditions and underwent a
      hypercoagulable evaluation. Screening was done in 4.7% of patients with early
      bypass graft thrombosis, 60% of patients were screened because of multiple bypass
      or graft thrombosis, and 35.3% had a previous history of DVT, PE, or native
      vessel thrombosis. Of the 43 patients with DM and 42 nDM evaluated, 59 patients
      (69%) had an abnormal hypercoagulable profile. An elevated heparin antibody level
      was present in 30% of DM and 12% of nDM patients (chi-squared test P < 0.04).
      Additionally, DM was associated with a higher likelihood of arterial
      complications while nDM was associated with a higher rate of venous adverse
      events (chi-squared test P < 0.003). Conclusions. Diabetes is associated with a
      higher likelihood of developing heparin-induced antibodies and an increased
      combined incidence of arterial complications that include early or multiple
      bypass/graft thrombosis. This finding may influence the choice of anticoagulation
      in diabetic patients at risk with vascular disease. 

PMID- 24672720
TI  - Thromboembolism Prevention via Transcatheter Left Atrial Appendage Closure with
      Transeosophageal Echocardiography Guidance.
AB  - Atrial fibrillation (AF) is an independent risk factor for stroke.
      Anticoagulation therapy has a risk of intracerebral hemorrhage. The use of
      percutaneous left atrial appendage (LAA) closure devices is an alternative to
      anticoagulation therapy. Echocardiography has a leading role in LAA closure
      procedure in patient selection, during the procedure and during followup. A
      comprehensive echocardiography study is necessary preprocedural in order to
      identify all the lobes of the LAA, evaluate the size of the LAA ostium, look for
      thrombus or spontaneous echo contrast, and evaluate atrial anatomy, including
      atrial septal defect and patent foramen ovale. Echocardiography is used to
      identify potential cardiac sources of embolism, such as atrial septal aneurysm,
      mitral valve disease, and aortic debris. During the LAA occlusion procedure
      transeosophageal echocardiography provides guidance for the transeptal puncture
      and monitoring during the release of the closure device. Procedure-related
      complications can be evaluated and acceptable device release criteria such as
      proper position and seating of the occluder in the LAA, compression, and
      stability can be assessed. Postprocedural echocardiography is used for followup
      to assess the closure of the LAA ostium. This overview paper describes the
      emerging role of LAA occlusion procedure with transeosophageal echocardiography
      guidance as an alternative to anticoagulation therapy in patients with AF. 

PMID- 24672721
TI  - A simple clinical measure of quadriceps muscle strength identifies responders to
      pulmonary rehabilitation.
AB  - The aim was to determine if baseline measures can predict response to pulmonary
      rehabilitation in terms of six-minute walk distance (6MWD) or quality of life.
      Participants with COPD who attended pulmonary rehabilitation between 2010 and
      2012 were recruited. Baseline measures evaluated included physical activity,
      quadriceps strength, comorbidities, inflammatory markers, and self-efficacy.
      Participants were classified as a responder with improvement in 6MWD (criteria of
      >=25 m or >=2SD) and Chronic Respiratory Questionnaire (CRQ; >=0.5
      points/question). Eighty-five participants with a mean (SD) age of 67(9) years
      and a mean forced expiratory volume in one second of 55(22)% were studied. Forty
      nine and 19 participants were responders when using the 6MWD criteria of >=25 m
      and >=61.9 m, respectively, with forty-four participants improving in CRQ. In a
      regression model, responders in 6MWD (>=25 m criteria) had lower baseline
      quadriceps strength (P = 0.028) and higher baseline self-efficacy scores (P =
      0.045). Independent predictors of 6MWD response (>=61.9 m criteria) were
      participants with metabolic disease (P = 0.007) and lower baseline quadriceps
      strength (P = 0.016). Lower baseline CRQ was the only independent predictor of
      CRQ response. A participant with relatively lower baseline quadriceps strength
      was the strongest independent predictor of 6MWD response. Metabolic disease may
      predict 6MWD response, but predictors of CRQ response remain unclear. 

PMID- 24672722
TI  - The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case
      Control Study.
AB  - Earlier reports showed the relationship between autism and immune genes located
      in the human leukocyte antigen (HLA). In this current study, we compared the HLA
      class I and class II alleles and haplotypes in 35 autistic children with 100
      control subjects from Saudi Arabia, using PCR-SSP method and Luminex technology.
      In class I the HLA-A*01 (P = 0.03, OR 2.68), A*02 (P = 0.001, OR 3.02) and HLA
      B*07 (P = 0.01, OR 3.27), were significantly associated with autism. Also, the
      haplotype A*02-B*07 was significantly higher in autistic patients than in
      controls (P = 0.007, OR 5.83). In class II, DRB1*1104 was significantly higher in
      patients than in controls (P = 0.001, OR 8.75). The DQB1*0202 (P = 0.001, OR
      0.24), DQB1*0302 (P = 0.001, OR 0.14), and DQB1*0501 (P = 0.012, OR 0.25), were
      negatively associated with disease. While the four-loci genotype study showed
      that A*01-B*07-DRB1*0701-DQB1*0602 (P = 0.001, OR 41.9) and the A*31-B*51
      DRB1*0103-DQB1*0302 (P = 0.012, OR 4.8) are positively associated with autism
      among Saudi patients. This is the first report on a foreseeable risk of
      association of HLA-B*07 allele with autism. Thus, HLA-B*07 allele and the closely
      linked haplotype A*01 B*07 DRB1*0701 DQB1*0602 may serve as a marker for genetic
      susceptibility to autism in Saudis. 

PMID- 24672723
TI  - A technique of predicting radiographic joint line and posterior femoral condylar
      offset of the knee.
AB  - Purpose. To describe a reliable method of predicting native joint line and
      posterior condylar offset (PCO) using true lateral digital radiographs of the
      distal femur. Methods. PCO was measured relative to a line drawn parallel to the
      posterior cortex of the distal femur and the joint line was measured from the
      posterior condylar flare to the articular surface. A ratio was then calculated
      for these measurements relative to the width of the femur at the level of the
      flare. Two independent observers measured PCO and joint line ratio for 105
      radiographs of the different knees and one repeated these measurements after one
      week. Results. There was a significant correlation between the width of the
      femoral diaphysis at the level of the posterior condylar flare with joint line (P
      = 0.008) and PCO (P = 0.003). Joint line and PCO could be predicted within 4 mm
      and 2 mm, respectively, using the identified ratio between the width of the
      femoral diaphysis at the level of the posterior condylar flare with measured
      joint line and PCO. The inter- (P < 0.001) and intra- (P < 0.001) observer
      reliability for these ratios were high. Conclusion. These ratios could be used to
      predict the native joint line and PCO. 

PMID- 24672724
TI  - Vascular endothelial growth factor and brain-derived neurotrophic factor in
      quetiapine treated first-episode psychosis.
AB  - Objective. It has been suggested that atypical antipsychotics confer their
      effects via brain-derived neurotrophic factor (BDNF). We investigated the effect
      of quetiapine on serum levels of BDNF and vascular endothelial growth factor
      (VEGF) in drug-naive first-episode psychosis subjects. Methods. Fifteen patients
      drawn from a larger study received quetiapine treatment for twelve weeks.
      Baseline levels of serum BDNF and VEGF were compared to age- and sex-matched
      healthy controls and to levels following treatment. Linear regression analyses
      were performed to determine the relationship of BDNF and VEGF levels with outcome
      measures at baseline and week 12. Results. The mean serum BDNF level was
      significantly higher at week 12 compared to baseline and correlated with
      reductions in Brief Psychiatric Rating Scale (BPRS) and general psychopathology
      scores. Changes in serum VEGF levels also correlated significantly with a
      reduction in BPRS scores, a significant improvement in PANNS positive symptoms
      scores, and displayed a positive relationship with changes in BDNF levels.
      Conclusions. Our findings suggest that BDNF and VEGF are potential biomarkers for
      gauging improvement of psychotic symptoms. This suggests a novel neurotrophic
      based mechanism of the drug effects of quetiapine on psychosis. This is the first
      report of VEGF perturbation in psychosis. 

PMID- 24672725
TI  - Cystatin C as a predictor of mortality and cardiovascular events in a population
      with chronic kidney disease.
AB  - Background. We examine whether cystatin C, a surrogate marker of renal function,
      could identify patients with chronic kidney disease (CKD) with an increased risk
      of renal disease progression, death, or cardiovascular events. Methods. Data were
      obtained for 180 patients, with a diagnosis of chronic renal failure based on
      serum creatinine estimated glomerular filtration rate (eGFRcreat) <90 mL/min/1.73
      m(2). This population was grouped in tertiles according to cystatin C and
      creatinine values at baseline. Cardiovascular events and overall mortality were
      estimated for each tertile. Predictors of overall mortality and for the
      development of renal disease progression were analyzed. Results. The median age
      was 75 years (interquartile range 69-82) and the median eGFRcreat 38 mL/min m(2)
      (interquartile range 33-49). Overall mortality was lower on the first and on the
      second tertiles of cystatin C than on the third one (HR = 0.060; 95% CI: 0.008
      0.447 and HR = 0.094; 95% CI: 0.022-0.406, resp.). Deaths related to the
      creatinine tertiles followed the same pattern, but differences were not as large.
      Cardiovascular mortality was lower on the second than on the third cystatin C
      tertile (HR = 0.198; 95% CI: 0.040-0.987), but it did not show differences on the
      first and the second creatinine tertiles compared with the third one (HR = 0.126;
      95% CI: 0.013-1.265 and HR = 0.403; 95% CI: 0.093-1.740). The only independent
      predictors of mortality during followup were baseline cystatin C (OR = 0.100; 95%
      CI: 0.021-0.463) and baseline uric acid (OR = 1.377; 95% CI: 1.070-1.773).
      Conclusion. Cystatin C may be an alternative to creatinine for detecting a high
      risk of death and cardiovascular events in a population with CKD. 

PMID- 24672726
TI  - Reference Ranges for Serum Uric Acid among Healthy Assamese People.
AB  - This study was designed to establish reference ranges for serum uric acid among
      healthy adult Assamese population. Samples from 1470 aged 35-86 years were used
      to establish age and sex related reference range by the centile method (central
      95 percentile) for serum uric acid level. There were 51% (n = 754) males and 49%
      (n = 716) females; 75.9% (n = 1115) of them were from urban area and the rest
      24.1% (n = 355) were from the rural area. Majority of the population were
      nonvegetarian (98.6%, n = 1450) and only 1.4% (n = 20) were vegetarian. The mean
      age, weight, height, and uric acid of the studied group were 53.6 +/- 11.3 years,
      62.6 +/- 10.5 kg, 160 +/- 9.4 cm, and 5.5 +/- 1.4 mg/dL, respectively. There is a
      statistically significant difference in the mean value of the abovementioned
      parameters between male and female. The observed reference range of uric acid in
      the population is 2.6-8.2 mg/dL which is wider than the current reference range
      used in the laboratory. Except gender (P < 0.0001), we did not find any
      significant relation of uric acid with other selected factors. 

PMID- 24672727
TI  - Production and Partial Purification of Alpha Amylase from Bacillus subtilis (MTCC
      121) Using Solid State Fermentation.
AB  - Amylase is an enzyme that catalyzes the breakdown of starch into sugars and plays
      a pivotal role in a variety of areas like use as digestives, for the production
      of ethanol and high fructose corn syrup, detergents, desiring of textiles,
      modified starches, hydrolysis of oil-field drilling fluids, and paper recycling.
      In the present work, solid state fermentation (SSF) for alpha -amylase production
      has been used in lieu of submerged fermentation (SmF) due to its simple
      technique, low capital investment, lower levels of catabolite repression, and
      better product recovery. Bacillus subtilis has been well known as producer of
      alpha amylase and was tested using solid state fermentation for 48 hours at 37
      degrees C with wheat bran as substrate. Comparison between different fermentation
      hours demonstrated high yield of alpha amylase after 48 hours. This alpha amylase
      has optimum pH and temperature at 7.1 and 40 degrees C, respectively. With the
      goal to purify alpha amylase, 30-70% (NH4)2SO4 cut concentrated the amylase
      activity threefold with respect to crude fermented extract. This was verified in
      quantitative DNS assay method as well as in zymogram gel profile. The exact
      molecular weight of the amylase is yet to be determined with the aid of other
      protein purification techniques. 

PMID- 24672728
TI  - The prevalence of familial multiple sclerosis in saskatoon, Saskatchewan.
AB  - Background. A population-based prevalent cohort of 150 clinical definite multiple
      sclerosis (MS) cases (102 women; 48 men) ascertained on January 1, 1977,
      Saskatoon, Saskatchewan, was found to have a familial rate of MS as 17.3%.
      Objectives. To determine the occurrence of familial MS cases and the frequency of
      MS among the biological relatives of the study cohort. Methods. The search for
      new familial cases MS affected relatives continued for 35 years until 2012. The
      natural history of the disease of sporadic cases is compared with that of the
      familial cases. SPSS V19 and Kaplan-Meier survival analysis were used for data
      analysis. Results. Of the 150 unrelated MS patients, 49 cases (32.7%) (36 women
      and 13 men) were reported of having at least one family member with MS. There
      were a total of 86 affected relatives, 26 (30.2%) first-degree relatives, 15
      (17.4%) second-degree relatives, 20 (23.3%) third-degree relatives, and 25
      (29.1%) distant relatives. The average age of MS onset for men with sporadic MS
      was 33.9 (SD = 10) years and 27.6 (SD = 8.4) years for familial cases and 29.3
      (SD = 8.3) years and 26.8 (SD = 8.5) years for women. Conclusion. This 35-year
      longitudinal natural history study reveals a high frequency of cases with family
      members developing MS and supports a genetic influence in the etiology of MS. 

PMID- 24672729
TI  - High Prevalence of Helicobacter pylori hopQ II Genotype Isolated from Iranian
      Patients with Gastroduodenal Disorders.
AB  - Helicobacter pylori plays an important role in the pathogenesis of chronic
      gastritis, peptic ulceration, and noncardia gastric cancer. Several putative
      virulence factors for H. pylori have been identified including vacA, babA, and
      iceA. HopQ is one of the outer membrane proteins involved in bacterial adherence
      to gastric mucosa and has been suggested to also play a role in the virulence of
      H. pylori. Due to the substantial geographic differences in the prevalence of H.
      pylori virulence factors reported, the main purpose of the current study was to
      investigate the association between different H. pylori virulence hopQ alleles
      (types I and II) and patients with gastroduodenal disorders. The presence of H.
      pylori and hopQ alleles in gastric biopsy specimens was identified by specific
      PCR assays. H. pylori type II hopQ was found to be significantly associated with
      gastric cancer patients (odds ratio: 3.47, 95% CI: 1.56-5.89). Information about
      the prevalence of H. pylori hopQ type II can be used for determining the high
      risk diseases type which is actually colonized by H. pylori hopQ type II positive
      strains. The presence of H. pylori hopQ type II should be investigated in
      different geographical regions as confirmatory findings may provide a definite
      biomarker attributed to the pathogenesis of certain severe digestive diseases. 

PMID- 24672730
TI  - Nodal status assessment in breast cancer: strategies of clinical grounds and
      quality of life implications.
AB  - Even in the era of gene-expression profiling, the nodal status still remains the
      primary prognostic discriminant in breast cancer patients. The exclusion of node
      involvement using noninvasive methods could reduce the rate of axillary surgery,
      thereby preventing from suffering complications. However, lymphatic mapping with
      sentinel node biopsy (SNB) is one of the most interesting recent developments in
      surgical oncology. Optimization of procedure could be implemented by dual mapping
      injection site skills, resection of all hot or blue nodes through tracer
      combination, and improvement in atypical drainage patterns mapping. This
      anatomical analysis suggests safety measures in patients with high probability of
      node metastasis through a renewed interest in surgical management. The
      perspective of a guided axillary sampling (GAS) could represent a potential
      development of recent anatomical and functional acquisitions, offering a dynamic
      technique shared according to clinical and anatomical disease parameters.
      Furthermore, the surgical staging procedures may adopt a conservative approach
      through the evaluation of upper arm lymphatics, thus defining a functional model
      aimed at the reduction of short- and long-term adverse events. Quality results in
      breast cancer surgery need to generate oncological safety devoid of complications
      through renewed clinical experience. 

PMID- 24672731
TI  - Daytime sleepiness: associations with alcohol use and sleep duration in
      americans.
AB  - The aim of the current analysis was to investigate the relationship of daytime
      sleepiness with alcohol consumption and sleep duration using a population sample
      of adult Americans. Data was analyzed from adult respondents of the National
      Health and Nutritional Examination Survey (NHANES) 2007-2008 (N = 2919) using
      self-reported variables for sleepiness, sleep duration, and alcohol consumption
      (quantity and frequency of alcohol use). A heavy drinking episode was defined as
      the consumption of >=5 standard alcoholic beverages in a day. Logistic regression
      models adjusted for sociodemographic variables and insomnia covariates were used
      to evaluate the relationship between daytime sleepiness and an interaction of
      alcohol consumption variables with sleep duration. The results showed that
      daytime sleepiness was reported by 15.07% of the subjects. In univariate analyses
      adjusted for covariates, an increased probability of daytime sleepiness was
      predicted by decreased log drinks per day [OR = 0.74 (95% CI, 0.58-0.95)], a
      decreased log drinking frequency [0.90 (95% CI, 0.83-0.98)], and lower sleep
      duration [OR = 0.75 (95% CI, 0.67-0.84)]. An interaction between decreased sleep
      duration and an increased log heavy drinking frequency predicted increased
      daytime sleepiness (P = 0.004). Thus, the effect of sleep duration should be
      considered when evaluating the relationship between daytime sleepiness and heavy
      drinking. 

PMID- 24672732
TI  - Blockade of alternative complement pathway in dense deposit disease.
AB  - A patient aged 17 with dense deposit disease associated with complement
      activation, circulating C3 Nef, and Factor H mutation presented with nephrotic
      syndrome and hypertension. Steroid therapy, plasma exchange, and rituximab failed
      to improve proteinuria and hypertension despite a normalization of the
      circulating sC5b9 complex. Eculizumab, a monoclonal antibody directed against C5,
      was used to block the terminal product of the complement cascade. The dose was
      adapted to achieve a CH50 below 10%, but proteinuria and blood pressure were not
      improved after 3 months of treatment. 

PMID- 24672733
TI  - Light and Darkness: Prevalence of Hepatitis E Virus Infection among the General
      Population.
AB  - Human hepatitis E virus (HHEV) spreads early in life among the population in
      areas endemic for genotype 1 and infects mainly adults in areas endemic for
      genotype 3, where it would be responsible for about 10% of cases of suspected
      acute viral hepatitis of unknown etiology and for a number of subclinical,
      unrecognized infections. The overall prevalence of antibody to HHEV is high in
      most of the former areas and low in most of the later ones, but wide regional
      differences have been recorded in both cases. "Hot spots" of HHEV infection would
      exist for both types of strains in particular regions or among particular
      populations of the world. Studies on pork derivatives, shellfish bivalves, and
      vegetables for HHEV contamination at the sale point need to be extended for
      evaluating the impact of the agent on food safety, and the meaning of the finding
      of HHEV genotype 1 genomes in urban sewage from developed countries should be
      established through active surveillance. Consensus about technical issues in
      regard to anti-HEV testing would improve the knowledge of the HHEV epidemiology.
      Studies in particular regions and populations, and introduction of molecular
      diagnosis in the clinical setting as a routine tool, would also be required. 

PMID- 24672735
TI  - Influenza viral manipulation of sphingolipid metabolism and signaling to modulate
      host defense system.
AB  - Viruses attempt to create a distinctive cellular environment to favor viral
      replication and spread. Recent studies uncovered new functions of the
      sphingolipid signaling/metabolism during pathogenic virus infections. While
      sphingolipids such as sphingomyelin and ceramide were reported to influence the
      entry step of several viruses, sphingolipid-metabolizing enzymes could directly
      alter viral replication processes. Influenza virus was shown to increase the
      level of sphingosine kinase (SK) 1 to promote virus propagation. The mechanism
      involves regulation of intracellular signaling pathways, leading to the
      amplification of influenza viral RNA synthesis and nuclear export of viral
      ribonucleoprotein (RNP) complex. However, bovine viral diarrhea virus inhibits
      SK1 to enhance the efficacy of virus replication, demonstrating the presence of
      virus-specific strategies for modulation of the sphingolipid system. Therefore,
      investigating the sphingolipid metabolism and signaling in the context of virus
      replication could help us design innovative therapeutic approaches to improve
      human health. 

PMID- 24672736
TI  - Mapping stain distribution in pathology slides using whole slide imaging.
AB  - BACKGROUND: Whole slide imaging (WSI) offers a novel approach to digitize and
      review pathology slides, but the voluminous data generated by this technology
      demand new computational methods for image analysis. MATERIALS AND METHODS: In
      this study, we report a method that recognizes stains in WSI data and uses kernel
      density estimator to calculate the stain density across the digitized pathology
      slides. The validation study was conducted using a rat model of acute cardiac
      allograft rejection and another rat model of heart ischemia/reperfusion injury.
      Immunohistochemistry (IHC) was conducted to label ED1(+) macrophages in the
      tissue sections and the stained slides were digitized by a whole slide scanner.
      The whole slide images were tessellated to enable parallel processing. Pixel-wise
      stain classification was conducted to classify the IHC stains from those of the
      background and the density distribution of the identified IHC stains was then
      calculated by the kernel density estimator. RESULTS: The regression analysis
      showed a correlation coefficient of 0.8961 between the number of IHC stains
      counted by our stain recognition algorithm and that by the manual counting,
      suggesting that our stain recognition algorithm was in good agreement with the
      manual counting. The density distribution of the IHC stains showed a consistent
      pattern with those of the cellular magnetic resonance (MR) images that detected
      macrophages labeled by ultrasmall superparamagnetic iron-oxide or micron-sized
      iron-oxide particles. CONCLUSIONS: Our method provides a new imaging modality to
      facilitate clinical diagnosis. It also provides a way to validate/correlate
      cellular MRI data used for tracking immune-cell infiltration in cardiac
      transplant rejection and cardiac ischemic injury.

PMID- 24672734
TI  - Themes and Variations: Regulation of RpoN-Dependent Flagellar Genes across
      Diverse Bacterial Species.
AB  - Flagellar biogenesis in bacteria is a complex process in which the transcription
      of dozens of structural and regulatory genes is coordinated with the assembly of
      the flagellum. Although the overall process of flagellar biogenesis is conserved
      among bacteria, the mechanisms used to regulate flagellar gene expression vary
      greatly among different bacterial species. Many bacteria use the alternative
      sigma factor sigma (54) (also known as RpoN) to transcribe specific sets of
      flagellar genes. These bacteria include members of the Epsilonproteobacteria
      (e.g., Helicobacter pylori and Campylobacter jejuni), Gammaproteobacteria (e.g.,
      Vibrio and Pseudomonas species), and Alphaproteobacteria (e.g., Caulobacter
      crescentus). This review characterizes the flagellar transcriptional hierarchies
      in these bacteria and examines what is known about how flagellar gene regulation
      is linked with other processes including growth phase, quorum sensing, and host
      colonization. 

PMID- 24672738
TI  - Mining genome sequencing data to identify the genomic features linked to breast
      cancer histopathology.
AB  - BACKGROUND: Genetics and genomics have radically altered our understanding of
      breast cancer progression. However, the genomic basis of various histopathologic
      features of breast cancer is not yet well-defined. MATERIALS AND METHODS: The
      Cancer Genome Atlas (TCGA) is an international database containing a large
      collection of human cancer genome sequencing data. cBioPortal is a web tool
      developed for mining these sequencing data. We performed mining of TCGA
      sequencing data in an attempt to characterize the genomic features correlated
      with breast cancer histopathology. We first assessed the quality of the TCGA data
      using a group of genes with known alterations in various cancers. Both genome
      wide gene mutation and copy number changes as well as a group of genes with a
      high frequency of genetic changes were then correlated with various
      histopathologic features of invasive breast cancer. RESULTS: Validation of TCGA
      data using a group of genes with known alterations in breast cancer suggests that
      the TCGA has accurately documented the genomic abnormalities of multiple
      malignancies. Further analysis of TCGA breast cancer sequencing data shows that
      accumulation of specific genomic defects is associated with higher tumor grade,
      larger tumor size and receptor negativity. Distinct groups of genomic changes
      were found to be associated with the different grades of invasive ductal
      carcinoma. The mutator role of the TP53 gene was validated by genomic sequencing
      data of invasive breast cancer and TP53 mutation was found to play a critical
      role in defining high tumor grade. CONCLUSIONS: Data mining of the TCGA genome
      sequencing data is an innovative and reliable method to help characterize the
      genomic abnormalities associated with histopathologic features of invasive breast
      cancer.

PMID- 24672737
TI  - The 2013 symposium on pathology data integration and clinical decision support
      and the current state of field.
AB  - BACKGROUND: Pathologists and informaticians are becoming increasingly interested
      in electronic clinical decision support for pathology, laboratory medicine and
      clinical diagnosis. Improved decision support may optimize laboratory test
      selection, improve test result interpretation and permit the extraction of
      enhanced diagnostic information from existing laboratory data. Nonetheless, the
      field of pathology decision support is still developing. To facilitate the
      exchange of ideas and preliminary studies, we convened a symposium entitled:
      Pathology data integration and clinical decision support. METHODS: The symposium
      was held at the Massachusetts General Hospital, on May 10, 2013. Participants
      were selected to represent diverse backgrounds and interests and were from nine
      different institutions in eight different states. RESULTS: The day included 16
      plenary talks and three panel discussions, together covering four broad areas.
      Summaries of each presentation are included in this manuscript. CONCLUSIONS: A
      number of recurrent themes emerged from the symposium. Among the most pervasive
      was the dichotomy between diagnostic data and diagnostic information, including
      the opportunities that laboratories may have to use electronic systems and
      algorithms to convert the data they generate into more useful information.
      Differences between human talents and computer abilities were described; well
      designed symbioses between humans and computers may ultimately optimize
      diagnosis. Another key theme related to the unique needs and challenges in
      providing decision support for genomics and other emerging diagnostic modalities.
      Finally, many talks relayed how the barriers to bringing decision support toward
      reality are primarily personnel, political, infrastructural and administrative
      challenges rather than technological limitations.

PMID- 24672739
TI  - Color standardization in whole slide imaging using a color calibration slide.
AB  - BACKGROUND: Color consistency in histology images is still an issue in digital
      pathology. Different imaging systems reproduced the colors of a histological
      slide differently. MATERIALS AND METHODS: Color correction was implemented using
      the color information of the nine color patches of a color calibration slide. The
      inherent spectral colors of these patches along with their scanned colors were
      used to derive a color correction matrix whose coefficients were used to convert
      the pixels' colors to their target colors. RESULTS: There was a significant
      reduction in the CIELAB color difference, between images of the same H & E
      histological slide produced by two different whole slide scanners by 3.42 units,
      P < 0.001 at 95% confidence level. CONCLUSION: Color variations in histological
      images brought about by whole slide scanning can be effectively normalized with
      the use of the color calibration slide.

PMID- 24672741
TI  - Significance of Anti-retinal Autoantibodies in Cancer-associated Retinopathy with
      Gynecological Cancers.
AB  - BACKGROUND: The presence of autoantibodies (AAbs) is the primary serological
      indicator of autoimmunity. Cancer-associated retinopathy (CAR) is associated with
      AAbs and different types of cancer. The goal of the study was to examine the
      profile of serum autoantibodies in women with gynecological cancers with and
      without paraneoplastic visual manifestation. METHODS: Retrospective studies of a
      cohort of 46 women with symptoms of CAR and gynecological tumors, including
      endometrial, cervical, ovarian, and fallopian tubes, 111 women with similar
      tumors without symptoms of CAR, and 60 age-matched healthy controls. Presence of
      serum AAbs and the identity of targeted antigens were performed by western
      blotting and their significance was evaluated using an Fisher's exact test.
      RESULTS: The patients with gynecological CAR had the highest proportion of
      seropositivity (80%), followed by patients with gynecological cancers without CAR
      (61%) and healthy controls (58%). Differences in recognition frequencies were
      found for 17 antigens and 5 retinal antigens were frequently targeted: enolase,
      aldolase C, carbonic anhydrase II, recoverin and GAPDH. The occurrence of anti
      glycolytic enzymes was 2-3 times more frequent in CAR and cancer patients than
      healthy controls. Anti-recoverin AAbs were prevalent in endometrial CAR. Anti
      CAII antibodies were not significantly different between groups of women. In this
      cohort, cancer was diagnosed before the onset of retinopathy with latency from 2
      months to 30 years. The discovery of the ovarian and endometrial cancers and
      manifestation of visual problems often coincided but Fallopian tube carcinoma was
      found after visual onset. CONCLUSION: New retinal targets were identified for
      gynecological CAR. Each gynecological-CAR has its own autoantibody profile
      different from non-CAR profile, implying that a complex autoantibody signature
      may be more predictable for diagnosis than a singular AAb. Specific anti-retinal
      AAbs were most prevalent in women with CAR but their profiles were not fully
      distinguished from cancer controls.

PMID- 24672740
TI  - Modes of Retinal Cell Death in Diabetic Retinopathy.
AB  - Cell death seems to be a prominent feature in the progression of diabetic
      retinopathy. Several retinal cell types have been identified to undergo cell
      death in a diabetic environment. Most emphasis has been directed towards
      identifying apoptosis in the diabetic retina. However, new research has
      established that there are multiple forms of cell death. This review discusses
      the different modes of cell death and attempts to classify cell death of retinal
      cells known to die in diabetic retinopathy. Special emphasis is given to
      apoptosis, necrosis, autophagic cell death, and pyroptosis. It seems that
      different retinal cell types are dying by diverse types of cell death. Whereas
      endothelial cells predominantly undergo apoptosis, pericytes might die by
      apoptosis as well as necrosis. On the other hand, Muller cells are suggested to
      die by a pyroptotic mechanism. Diabetes leads to significant Muller cell loss at
      7 months duration of diabetes in retinas of diabetic mice compared to non
      diabetic, which is prevented by the inhibition of the caspase-1/IL-1beta
      (interleukin-1beta) pathway using the IL-1 receptor knockout mouse. Since
      pyroptosis is characterized by the activation of the caspase-1/IL-1beta pathway
      subsequently leading to cell death, Muller cells seem to be a prime candidate for
      this form of inflammation-driven cell death. Considering that diabetic
      retinopathy is now discussed to potentially be a chronic inflammatory disease,
      pyroptotic cell death might play an important role in disease progression.
      Understanding mechanisms of cell death will lead to a more targeted approach in
      the development of new therapies to treat diabetic retinopathy.

PMID- 24672742
TI  - Erythropoiesis-stimulating Agent Use among Patients with Lupus Nephritis
      Approaching End-stage Renal Disease.
AB  - OBJECTIVES: Little is known about erythropoiesis-stimulating agents (ESAs)
      utilization among lupus nephritis (LN) patients with incipient ESRD. We aimed to
      identify sociodemographic and clinical factors associated with ESA use among
      incident LN ESRD patients. METHODS: Among all individuals age >=18 with incident
      ESRD from 1995-2008 in the U.S. Renal Data System (USRDS), we identified those
      with systemic lupus erythematosus (ICD-9 code 710.0) as the cause of ESRD. ESA
      use at ESRD onset was ascertained from the Medical Evidence Report. Year of
      onset, age, sex, race/ethnicity, medical insurance, employment status,
      residential region, clinical factors and comorbidities were considered
      potentially associated with ESA use in multivariable-adjusted logistic regression
      analyses. RESULTS: We identified 12,533 individuals with incident LN ESRD (1% of
      entire population). Of those, 4,288 (34%) received an ESA preceding ESRD. In
      multivariable-adjusted models, ESA users had higher serum albumin and hemoglobin
      concentrations, were more likely to be women, and to live in the Northeast.
      Conversely, Medicaid beneficiaries, the uninsured, unemployed, African Americans,
      Hispanics, and those with IV drug use, congestive heart failure and obesity had
      lower ESA use. CONCLUSION: Among all U.S. patients and those with LN who
      developed ESRD, approximately one third received ESAs. Patient sex, race, age,
      medical insurance, residential region and clinical factors were significantly
      associated with ESA therapy. While there are no guidelines for ESA use in LN
      patients approaching ESRD, there has been wide sociodemographic variation,
      raising questions about ESA prescription practices.

PMID- 24672743
TI  - Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.
AB  - Diffusion tensor imaging (DTI) has shown microstructural abnormalities in
      patients with Huntington's Disease (HD) and work is underway to characterise how
      these abnormalities change with disease progression. Using methods that will be
      applied in longitudinal research, we sought to establish the reliability of DTI
      in early HD patients and controls. Test-retest reliability, quantified using the
      intraclass correlation coefficient (ICC), was assessed using region-of-interest
      (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from
      22 participants (10 early HD, 12 controls). T1 data was used to generate further
      ROIs for analysis in a reduced sample of 18 participants. The results suggest
      that fractional anisotropy (FA) and other diffusivity metrics are generally
      highly reliable, with ICCs indicating considerably lower within-subject compared
      to between-subject variability in both HD patients and controls. Where ICC was
      low, particularly for the diffusivity measures in the caudate and putamen, this
      was partly influenced by outliers. The analysis suggests that the specific DTI
      methods used here are appropriate for cross-sectional research in HD, and give
      confidence that they can also be applied longitudinally, although this requires
      further investigation. An important caveat for DTI studies is that test-retest
      reliability may not be evenly distributed throughout the brain whereby highly
      anisotropic white matter regions tended to show lower relative within-subject
      variability than other white or grey matter regions. 

PMID- 24672745
TI  - Topological and Historical Considerations for Infectious Disease Transmission
      among Injecting Drug Users in Bushwick, Brooklyn (USA).
AB  - Recent interest by physicists in social networks and disease transmission factors
      has prompted debate over the topology of degree distributions in sexual networks.
      Social network researchers have been critical of "scale-free" Barabasi-Albert
      approaches, and largely rejected the preferential attachment, "rich-get-richer"
      assumptions that underlie that model. Instead, research on sexual networks has
      pointed to the importance of homophily and local sexual norms in dictating degree
      distributions, and thus disease transmission thresholds. Injecting Drug User
      (IDU) network topologies may differ from the emerging models of sexual networks,
      however. Degree distribution analysis of a Brooklyn, NY, IDU network indicates a
      different topology than the spanning tree configurations discussed for sexual
      networks, instead featuring comparatively short cycles and high concurrency. Our
      findings suggest that IDU networks do in some ways conform to a "scale-free"
      topology, and thus may represent "reservoirs" of potential infection despite
      seemingly low transmission thresholds.

PMID- 24672744
TI  - Human Bone Marrow- and Adipose Tissue-derived Mesenchymal Stromal Cells are
      Immunosuppressive In vitro and in a Humanized Allograft Rejection Model.
AB  - BACKGROUND: Recent studies with bone marrow (BM)-derived Mesenchymal Stromal
      Cells (MSC) in transplant recipients demonstrate that treatment with MSC is safe
      and clinically feasible. While BM is currently the preferred source of MSC,
      adipose tissue is emerging as an alternative. To develop efficient therapies,
      there is a need for preclinical efficacy studies in transplantation. We used a
      unique humanized transplantation model to study the in vivo immunosuppressive
      effect of human BM-MSC and adipose tissue-derived MSC (ASC). METHODS: Gene
      expression of BM-MSC and ASC and their capacity to inhibit activated PBMC
      proliferation was evaluated. The in vivo immunosuppressive effect of BM-MSC and
      ASC was studied in a humanized mouse model. SCID mice were transplanted with
      human skin grafts and injected with human allogeneic PBMC with or without
      administration of BM-MSC or ASC. The effect of MSC on skin graft rejection was
      studied by immunohistochemistry and PCR. RESULTS: BM-MSC and ASC expressed
      TGFbeta, CXCL-10 and IDO. IDO expression and acitivity increased significantly in
      BM-MSC and ASC upon IFN-gamma stimulation. IFN-gamma stimulated BM-MSC and ASC
      inhibited the proliferation of activated PBMC in a significant and dose dependent
      manner. In our humanized mouse model, alloreactivity was marked by pronounced
      CD45+ T-cell infiltrates consisting of CD4+ and CD8+ T cells and increased IFN
      gamma expression in the skin grafts which were all significantly inhibited by
      both BM-MSC and ASC. CONCLUSION: BM-MSC and ASC are immunosuppressive in vitro
      and suppress alloreactivity in a preclinical humanized transplantation model.

PMID- 24672746
TI  - Estimating the Size of the Methamphetamine-Using Population in New York City
      Using Network Sampling Techniques.
AB  - As part of a recent study of the dynamics of the retail market for
      methamphetamine use in New York City, we used network sampling methods to
      estimate the size of the total networked population. This process involved
      sampling from respondents' list of co-use contacts, which in turn became the
      basis for capture-recapture estimation. Recapture sampling was based on links to
      other respondents derived from demographic and "telefunken" matching procedures
      the latter being an anonymized version of telephone number matching. This paper
      describes the matching process used to discover the links between the solicited
      contacts and project respondents, the capture-recapture calculation, the
      estimation of "false matches", and the development of confidence intervals for
      the final population estimates. A final population of 12,229 was estimated, with
      a range of 8235 - 23,750. The techniques described here have the special virtue
      of deriving an estimate for a hidden population while retaining respondent
      anonymity and the anonymity of network alters, but likely require larger sample
      size than the 132 persons interviewed to attain acceptable confidence levels for
      the estimate.

PMID- 24672747
TI  - Use of Computer Navigation in Orthopedic Oncology.
AB  - The use of computer navigation was first described in the surgical resection of
      pelvic tumors in 2004. It was developed to improve surgical accuracy with the
      goal of achieving clear resection margins and better oncologic results. During
      the past few years, there has been tremendous advancement of computer-assisted
      tumor surgery (CATS) in the field of orthopedic oncology. Currently, CATS with
      image fusion offers preoperative three-dimensional surgical planning and allows
      surgeons to reproduce the intended bone resections in musculoskeletal tumors. The
      technique is reported to be useful in technically demanding resections, such as
      in pelvic and sacral tumors; joint-preserving intercalated and multiplanar tumor
      resection; and complex reconstruction with custom computer-aided design
      prostheses or allografts. This article provides an up-to-date review of the
      recent developments and key features in CATS, its current status in clinical
      practice, and future directions in its development.

PMID- 24672748
TI  - In Vivo and in vitro dynamics of undifferentiated embryonic cell transcription
      factor 1.
AB  - Pluripotent stem cells retain the ability to differentiate into the three germ
      layers and germline. As a result, there is a major interest in characterizing
      regulators that establish and maintain pluripotency. The network of transcription
      factors continues to expand in complexity, and one factor, undifferentiated
      embryonic cell transcription factor 1 (UTF1), has recently moved more into the
      limelight. To facilitate the study of UTF1, we report the generation and
      characterization of two reporter lines that enable efficient tracking, mapping,
      and purification of endogenous UTF1. In particular, we include a built-in
      biotinylation system in our targeted locus that allows efficient and reliable
      pulldown. We also use this reporter to show the dynamic regulation of Utf1 in
      distinct stem cell conditions and demonstrate its utility for reprogramming
      studies. The multipurpose design of the reporter lines enables many directions of
      future study and should lead to a better understanding of UTF1's diverse roles. 

PMID- 24672749
TI  - Coordination of engineered factors with TET1/2 promotes early-stage epigenetic
      modification during somatic cell reprogramming.
AB  - Somatic cell reprogramming toward induced pluripotent stem cells (iPSCs) holds
      great promise in future regenerative medicine. However, the reprogramming process
      mediated by the traditional defined factors (OSMK) is slow and extremely
      inefficient. Here, we develop a combination of modified reprogramming factors
      (OySyNyK) in which the transactivation domain of the Yes-associated protein is
      fused to defined factors and establish a highly efficient and rapid reprogramming
      system. We show that the efficiency of OySyNyK-induced iPSCs is up to 100-fold
      higher than the OSNK and the reprogramming by OySyNyK is very rapid and is
      initiated in 24 hr. We find that OySyNyK factors significantly increase Tet1
      expression at the early stage and interact with Tet1/2 to promote reprogramming.
      Our studies not only establish a rapid and highly efficient iPSC reprogramming
      system but also uncover a mechanism by which engineered factors coordinate with
      TETs to regulate 5hmC-mediated epigenetic control. 

PMID- 24672750
TI  - Five transcription factors and FGF pathway inhibition efficiently induce
      erythroid differentiation in the epiblast.
AB  - Primitive erythropoiesis follows a stereotypic developmental program of mesoderm
      ventralization and internalization, hemangioblast formation and migration, and
      erythroid lineage specification. Induction of erythropoiesis is inefficient in
      either ES/iPS cells in vitro or nonhemangioblast cell populations in vivo. Using
      the chick model, we report that epiblast cells can be directly and efficiently
      differentiated into the erythroid lineage by expressing five hematopoietic
      transcription regulators (SCL+LMO2+GATA2+LDB1+E2A) and inhibiting the FGF
      pathway. We show that these five genes are expressed with temporal specificity
      during normal erythropoiesis. Initiation of SCL and LMO2 expression requires FGF
      activity, whereas erythroid differentiation is enhanced by FGF inhibition. The
      lag between hematopoiesis and erythropoiesis is attributed to sequential
      coregulator expression and hemangioblast migration. Globin gene transcription can
      be ectopically and prematurely induced by manipulating the availability of these
      factors and the FGF pathway activity. We propose that similar approaches can be
      taken for efficient erythroid differentiation in vitro. 

PMID- 24672751
TI  - Engineered biomaterials control differentiation and proliferation of human
      embryonic-stem-cell-derived cardiomyocytes via timed Notch activation.
AB  - For cell-based treatments of myocardial infarction, a better understanding of key
      developmental signaling pathways and more robust techniques for producing
      cardiomyocytes are required. Manipulation of Notch signaling has promise as it
      plays an important role during cardiovascular development, but previous studies
      presented conflicting results that Notch activation both positively and
      negatively regulates cardiogenesis. We developed surface- and microparticle-based
      Notch-signaling biomaterials that function in a time-specific activation-tunable
      manner, enabling precise investigation of Notch activation at specific
      developmental stages. Using our technologies, a biphasic effect of Notch
      activation on cardiac differentiation was found: early activation in
      undifferentiated human embryonic stem cells (hESCs) promotes ectodermal
      differentiation, activation in specified cardiovascular progenitor cells
      increases cardiac differentiation. Signaling also induces cardiomyocyte
      proliferation, and repeated doses of Notch-signaling microparticles further
      enhance cardiomyocyte population size. These results highlight the diverse
      effects of Notch activation during cardiac development and provide approaches for
      generating large quantities of cardiomyocytes. 

PMID- 24672752
TI  - Quality metrics for stem cell-derived cardiac myocytes.
AB  - Advances in stem cell manufacturing methods have made it possible to produce stem
      cell-derived cardiac myocytes at industrial scales for in vitro muscle physiology
      research purposes. Although FDA-mandated quality assurance metrics address safety
      issues in the manufacture of stem cell-based products, no standardized guidelines
      currently exist for the evaluation of stem cell-derived myocyte functionality. As
      a result, it is unclear whether the various stem cell-derived myocyte cell lines
      on the market perform similarly, or whether any of them accurately recapitulate
      the characteristics of native cardiac myocytes. We propose a multiparametric
      quality assessment rubric in which genetic, structural, electrophysiological, and
      contractile measurements are coupled with comparison against values for these
      measurements that are representative of the ventricular myocyte phenotype. We
      demonstrated this procedure using commercially available, mass-produced murine
      embryonic stem cell- and induced pluripotent stem cell-derived myocytes compared
      with a neonatal mouse ventricular myocyte target phenotype in coupled in vitro
      assays. 

PMID- 24672753
TI  - Modeling hippocampal neurogenesis using human pluripotent stem cells.
AB  - The availability of human pluripotent stem cells (hPSCs) offers the opportunity
      to generate lineage-specific cells to investigate mechanisms of human diseases
      specific to brain regions. Here, we report a differentiation paradigm for hPSCs
      that enriches for hippocampal dentate gyrus (DG) granule neurons. This
      differentiation paradigm recapitulates the expression patterns of key
      developmental genes during hippocampal neurogenesis, exhibits characteristics of
      neuronal network maturation, and produces PROX1+ neurons that functionally
      integrate into the DG. Because hippocampal neurogenesis has been implicated in
      schizophrenia (SCZD), we applied our protocol to SCZD patient-derived human
      induced pluripotent stem cells (hiPSCs). We found deficits in the generation of
      DG granule neurons from SCZD hiPSC-derived hippocampal NPCs with lowered levels
      of NEUROD1, PROX1, and TBR1, reduced neuronal activity, and reduced levels of
      spontaneous neurotransmitter release. Our approach offers important insights into
      the neurodevelopmental aspects of SCZD and may be a promising tool for drug
      screening and personalized medicine. 

PMID- 24672754
TI  - Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea.
AB  - The prevalence of hearing loss after damage to the mammalian cochlea has been
      thought to be due to a lack of spontaneous regeneration of hair cells, the
      primary receptor cells for sound. Here, we show that supporting cells, which
      surround hair cells in the normal cochlear epithelium, differentiate into new
      hair cells in the neonatal mouse following ototoxic damage. Using lineage
      tracing, we show that new hair cells, predominantly outer hair cells, arise from
      Lgr5-expressing inner pillar and third Deiters cells and that new hair cell
      generation is increased by pharmacological inhibition of Notch. These data
      suggest that the neonatal mammalian cochlea has some capacity for hair cell
      regeneration following damage alone and that Lgr5-positive cells act as hair cell
      progenitors in the cochlea. 

PMID- 24672755
TI  - Intrinsically active and pacemaker neurons in pluripotent stem cell-derived
      neuronal populations.
AB  - Neurons generated from pluripotent stem cells (PSCs) self-organize into
      functional neuronal assemblies in vitro, generating synchronous network
      activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous
      activities that are independent of external stimulation, suggesting the presence
      of thus far undetected intrinsically active neurons (IANs). Here, by using mouse
      embryonic stem cells, we provide evidence for the existence of IANs in PSC
      neuronal networks based on extracellular multielectrode array and intracellular
      patch-clamp recordings. IANs remain active after pharmacological inhibition of
      fast synaptic communication and possess intrinsic mechanisms required for
      autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC
      neuronal populations, contribute to synchronous network bursting, and exhibit
      pacemaker properties. The intrinsic activity and pacemaker properties of the
      neuronal subpopulation identified herein may be particularly relevant for
      interventions involving transplantation of neural tissues. IANs may be a key
      element in the regulation of the functional activity of grafted as well as
      preexisting host neuronal networks. 

PMID- 24672756
TI  - Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors
      by cell sorting for successful transplantation.
AB  - Human induced pluripotent stem cells (iPSCs) can provide a promising source of
      midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson's
      disease. However, iPSC-derived donor cells inevitably contain tumorigenic or
      inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells
      can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We
      induced DA neurons using scalable culture conditions on human laminin fragment,
      and the sorted CORIN(+) cells expressed the midbrain DA progenitor markers, FOXA2
      and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN(+) cells
      survived and differentiated into midbrain DA neurons in vivo, resulting in
      significant improvement of the motor behavior, without tumor formation. In
      particular, the CORIN(+) cells in a NURR1(+) cell-dominant stage exhibited the
      best survival and function as DA neurons. Our method is a favorable strategy in
      terms of scalability, safety, and efficiency and may be advantageous for clinical
      application. 

PMID- 24672757
TI  - Counteracting activities of OCT4 and KLF4 during reprogramming to pluripotency.
AB  - Differentiated cells can be reprogrammed into induced pluripotent stem cells
      (iPSCs) after overexpressing four transcription factors, of which Oct4 is
      essential. To elucidate the role of Oct4 during reprogramming, we investigated
      the immediate transcriptional response to inducible Oct4 overexpression in
      various somatic murine cell types using microarray analysis. By downregulating
      somatic-specific genes, Oct4 induction influenced each transcriptional program in
      a unique manner. A significant upregulation of pluripotent markers could not be
      detected. Therefore, OCT4 facilitates reprogramming by interfering with the
      somatic transcriptional network rather than by directly initiating a pluripotent
      gene-expression program. Finally, Oct4 overexpression upregulated the gene Mgarp
      in all the analyzed cell types. Strikingly, Mgarp expression decreases during the
      first steps of reprogramming due to a KLF4-dependent inhibition. At later stages,
      OCT4 counteracts the repressive activity of KLF4, thereby enhancing Mgarp
      expression. We show that this temporal expression pattern is crucial for the
      efficient generation of iPSCs. 

PMID- 24672758
TI  - Platform for induction and maintenance of transgene-free hiPSCs resembling ground
      state pluripotent stem cells.
AB  - Cell banking, disease modeling, and cell therapy applications have placed
      increasing demands on hiPSC technology. Specifically, the high-throughput
      derivation of footprint-free hiPSCs and their expansion in systems that allow
      scaled production remains technically challenging. Here, we describe a platform
      for the rapid, parallel generation, selection, and expansion of hiPSCs using
      small molecule pathway inhibitors in stage-specific media compositions. The
      platform supported efficient and expedited episomal reprogramming using just
      OCT4/SOX2/SV40LT combination (0.5%-4.0%, between days 12 and 16) in a completely
      feeder-free environment. The resulting hiPSCs are transgene-free, readily
      cultured, and expanded as single cells while maintaining a homogeneous and
      genomically stable pluripotent population. hiPSCs generated or maintained in the
      media compositions described exhibit properties associated with the ground state
      of pluripotency. The simplicity and robustness of the system allow for the high
      throughput generation and rapid expansion of a uniform hiPSC product that is
      applicable to industrial and clinical-grade use. 

PMID- 24672759
TI  - A rapid and efficient 2D/3D nuclear segmentation method for analysis of early
      mouse embryo and stem cell image data.
AB  - Segmentation is a fundamental problem that dominates the success of microscopic
      image analysis. In almost 25 years of cell detection software development, there
      is still no single piece of commercial software that works well in practice when
      applied to early mouse embryo or stem cell image data. To address this need, we
      developed MINS (modular interactive nuclear segmentation) as a MATLAB/C++-based
      segmentation tool tailored for counting cells and fluorescent intensity
      measurements of 2D and 3D image data. Our aim was to develop a tool that is
      accurate and efficient yet straightforward and user friendly. The MINS pipeline
      comprises three major cascaded modules: detection, segmentation, and cell
      position classification. An extensive evaluation of MINS on both 2D and 3D
      images, and comparison to related tools, reveals improvements in segmentation
      accuracy and usability. Thus, its accuracy and ease of use will allow MINS to be
      implemented for routine single-cell-level image analyses. 

PMID- 24672761
TI  - Rule-based Method for Extent and Localization of Myocardial Infarction by
      Extracted Features of ECG Signals using Body Surface Potential Map Data.
AB  - In this study, a method for determining the location and extent of myocardial
      infarction using Body Surface Potential Map data of PhysioNet challenge 2007
      database is presented. This data is related to four patients with myocardial
      infarction. We used two patients as training set to determine rules and two other
      patients as testing set of the proposed model. First, T-wave amplitude, T-wave
      integral, Q-wave amplitude and R-wave amplitude as four features of ECG signals
      were extracted. Then we defined several rules and proper thresholds for
      localization and determining the extent of myocardial infarction. To determine
      the precise location and extent of myocardial infarction, 17-segment standard
      model of left ventricle was used. Finally, overall accuracy of this method was
      shown with SO, CED and EPD parameters. We obtained 1.16, 1 and 5.3952 for SO, CED
      and EPD, respectively, in our test data. Two main advantages of this method are
      simplicity and high accuracy. 

PMID- 24672762
TI  - A fast algorithm for exonic regions prediction in DNA sequences.
AB  - The main purpose of this paper is to introduce a fast method for gene prediction
      in DNA sequences based on the period-3 property in exons. First, the symbolic DNA
      sequences were converted to digital signal using the electron ion interaction
      potential method. Then, to reduce the effect of background noise in the period-3
      spectrum, we used the discrete wavelet transform at three levels and applied it
      on the input digital signal. Finally, the Goertzel algorithm was used to extract
      period-3 components in the filtered DNA sequence. The proposed algorithm leads to
      decrease the computational complexity and hence, increases the speed of the
      process. Detection of small size exons in DNA sequences, exactly, is another
      advantage of the algorithm. The proposed algorithm ability in exon prediction was
      compared with several existing methods at the nucleotide level using: (i)
      specificity - sensitivity values; (ii) receiver operating curves (ROC); and (iii)
      area under ROC curve. Simulation results confirmed that the proposed method can
      be used as a promising tool for exon prediction in DNA sequences. 

PMID- 24672763
TI  - Medical X-ray Image Hierarchical Classification Using a Merging and Splitting
      Scheme in Feature Space.
AB  - Due to the daily mass production and the widespread variation of medical X-ray
      images, it is necessary to classify these for searching and retrieving proposes,
      especially for content-based medical image retrieval systems. In this paper, a
      medical X-ray image hierarchical classification structure based on a novel
      merging and splitting scheme and using shape and texture features is proposed. In
      the first level of the proposed structure, to improve the classification
      performance, similar classes with regard to shape contents are grouped based on
      merging measures and shape features into the general overlapped classes. In the
      next levels of this structure, the overlapped classes split in smaller classes
      based on the classification performance of combination of shape and texture
      features or texture features only. Ultimately, in the last levels, this procedure
      is also continued forming all the classes, separately. Moreover, to optimize the
      feature vector in the proposed structure, we use orthogonal forward selection
      algorithm according to Mahalanobis class separability measure as a feature
      selection and reduction algorithm. In other words, according to the complexity
      and inter-class distance of each class, a sub-space of the feature space is
      selected in each level and then a supervised merging and splitting scheme is
      applied to form the hierarchical classification. The proposed structure is
      evaluated on a database consisting of 2158 medical X-ray images of 18 classes
      (IMAGECLEF 2005 database) and accuracy rate of 93.6% in the last level of the
      hierarchical structure for an 18-class classification problem is obtained. 

PMID- 24672764
TI  - Detection and segmentation of erythrocytes in blood smear images using a line
      operator and watershed algorithm.
AB  - Most of the erythrocyte related diseases are detectable by hematology images
      analysis. At the first step of this analysis, segmentation and detection of blood
      cells are inevitable. In this study, a novel method using a line operator and
      watershed algorithm is rendered for erythrocyte detection and segmentation in
      blood smear images, as well as reducing over-segmentation in watershed algorithm
      that is useful for segmentation of different types of blood cells having partial
      overlap. This method uses gray scale structure of blood cell, which is obtained
      by exertion of Euclidian distance transform on binary images. Applying this
      transform, the gray intensity of cell images gradually reduces from the center of
      cells to their margins. For detecting this intensity variation structure, a line
      operator measuring gray level variations along several directional line segments
      is applied. Line segments have maximum and minimum gray level variations has a
      special pattern that is applicable for detections of the central regions of
      cells. Intersection of these regions with the signs which are obtained by
      calculating of local maxima in the watershed algorithm was applied for cells'
      centers detection, as well as a reduction in over-segmentation of watershed
      algorithm. This method creates 1300 sign in segmentation of 1274 erythrocytes
      available in 25 blood smear images. Accuracy and sensitivity of the proposed
      method are equal to 95.9% and 97.99%, respectively. The results show the proposed
      method's capability in detection of erythrocytes in blood smear images. 

PMID- 24672765
TI  - Monte Carlo Simulation of Siemens ONCOR Linear Accelerator with BEAMnrc and
      DOSXYZnrc Code.
AB  - The Monte Carlo method is the most accurate method for simulation of radiation
      therapy equipment. The linear accelerators (linac) are currently the most widely
      used machines in radiation therapy centers. In this work, a Monte Carlo modeling
      of the Siemens ONCOR linear accelerator in 6 MV and 18 MV beams was performed.
      The results of simulation were validated by measurements in water by ionization
      chamber and extended dose range (EDR2) film in solid water. The linac's X-ray
      particular are so sensitive to the properties of primary electron beam. Square
      field size of 10 cm * 10 cm produced by the jaws was compared with ionization
      chamber and film measurements. Head simulation was performed with BEAMnrc and
      dose calculation with DOSXYZnrc for film measurements and 3ddose file produced by
      DOSXYZnrc analyzed used homemade MATLAB program. At 6 MV, the agreement between
      dose calculated by Monte Carlo modeling and direct measurement was obtained to
      the least restrictive of 1%, even in the build-up region. At 18 MV, the agreement
      was obtained 1%, except for in the build-up region. In the build-up region, the
      difference was 1% at 6 MV and 2% at 18 MV. The mean difference between
      measurements and Monte Carlo simulation is very small in both of ONCOR X-ray
      energy. The results are highly accurate and can be used for many applications
      such as patient dose calculation in treatment planning and in studies that model
      this linac with small field size like intensity-modulated radiation therapy
      technique. 

PMID- 24672766
TI  - Prediction of Arterial Blood pH and Partial Pressure of Carbon dioxide from
      Venous Blood Samples in Patients Receiving Mechanical Ventilation.
AB  - Substitution of arterial with venous blood samples to estimate blood gas status
      is highly preferable due to practical and safety concerns. Numerous studies
      support the substitution of arterial by venous blood samples, reporting strong
      correlations between arterial and venous values. This study further investigated
      the predictive ability of venous blood samples for arterial Acid-Base Balance
      (pH) and pressure of carbon dioxide (pCO2). Participants were 51 post-brain
      surgery patients receiving mechanical ventilation, who had blood samples taken
      simultaneously from radial artery of the wrist and elbow vein. Results showed
      significant associations between arterial and venous pH and pCO2. However, the
      variation of regression residuals was not homogenous, and the regression line did
      not fit properly to the data, indicating that simple linear regression is sub
      optimal for prediction of arterial pH and pCO2 by venous blood sample. Although
      highly significant correlations were found between arterial and venous blood pH
      and pCO2, the results did not support the reliability of prediction of arterial
      blood pH and pCO2 by venous blood samples across a range of concentrations. 

PMID- 24672767
TI  - Are speech attractor models useful in diagnosing vocal fold pathologies?

PMID- 24672768
TI  - Designing and implementing bioimpedance spectroscopy device by measuring
      impedance in a mouse tissue.
AB  - Studies show that any complications including hemorrhage, lack of blood supply,
      lack of oxygen supply and death of cells in a tissue, will have a clear effect on
      electrical properties of that tissue. Thus, by measuring impedance of a set of
      tissues, potential problems of the damaged tissue may be found. Since electrical
      impedance is closely related to the measuring frequency, obviously, every tissue
      exhibits its own specific impedance according to its electrical properties at
      each frequency. This research project investigates design and manufacture method
      of a device for measuring tissue impedance at different frequencies. To this end,
      design of a multi frequency sinusoidal current source is required. This current
      source is built using a single harmonic Generator sample (Direct Digital
      Synthesizer AD9835) with working frequency (design-point frequency) between 1 Hz
      and 10 MHz and accuracy of 1 Hz and microcontroller (PIC16F628) capability. For
      measurement and display of tissue impedance, ARM AT91SAMs256 microcontroller was
      used. Thus, with this hardware created, it shows that there are significant
      impedance changes between mouse tissues. 

PMID- 24672769
TI  - Pathologic collision of inverted papilloma with esthesioneuroblastoma.
AB  - BACKGROUND: Inverted papilloma (IP) of the nasal cavity is a benign tumor that
      represents 0.5-4% of all nasal tumors and have been known to rarely undergo
      malignant transformation to squamous carcinoma and even more rarely
      adenocarcinoma. Synchronous association with low-grade esthesioneuroblastoma
      (ENB) has been reported in only one case report where a small-sized lesion was
      treated with surgery alone. Here we report the first case of invasion of IP by
      high-grade ENB with nodal metastasis that was treated with combined modality
      therapy. CASE PRESENTATION: A case of a 64-year-old African American gentleman
      presented to the otolaryngology with a 3-month history of recurrent epistaxis.
      Imaging revealed a large right nasal cavity mass extending into the right
      sphenoid sinus but without intracranial extension. Surgical pathology revealed
      high-grade ENB invading IP. An orbitofrontal craniotomy approach was used to
      achieve complete resection of the mass but with positive margins. Post-operative
      positron emission tomography/computed tomography showed nodal metastasis. The
      patient was then treated with adjuvant chemoradiation and remains without
      evidence of disease at 42 months post-treatment. We discuss the disease
      presentation, histopathologic features, and disease management with literature
      support. CONCLUSION: In this very rare disease presentation where two extremely
      rare malignancies collide, we show that aggressive management with trimodality
      therapy of surgery, adjuvant radiation with stereotactic radiosurgical boost, and
      adjuvant chemotherapy gives excellent results. Given the natural history of the
      disease, however, long follow-up is needed to declare complete freedom from the
      disease.

PMID- 24672770
TI  - Distribution of Human Papillomavirus Genotypes among HIV-Positive and HIV
      Negative Women in Cape Town, South Africa.
AB  - OBJECTIVE: HIV-positive women are known to be at high-risk of human
      papillomavirus (HPV) infection and its associated cervical pathology. Here, we
      describe the prevalence and distribution of HPV genotypes among HIV-positive and 
      negative women in South Africa, with and without cervical intraepithelial
      neoplasia (CIN). METHODS: We report data on 1,371 HIV-positive women and 8,050
      HIV-negative women, aged 17-65 years, recruited into three sequential studies in
      Cape Town, South Africa, conducted among women who had no history of cervical
      cancer screening recruited from the general population. All women were tested for
      HIV. Cervical samples were tested for high-risk HPV DNA (Hybrid Capture 2) with
      positive samples tested to determine the specific genotype (Line Blot). CIN
      status was determined based on colposcopy and biopsy. RESULTS: The HPV prevalence
      was higher among HIV-positive women (52.4%) than among HIV-negative women (20.8%)
      overall and in all age groups. Younger women, aged 17-19 years, had the highest
      HPV prevalence regardless of HIV status. HIV-positive women were more likely to
      have CIN 2 or 3 than HIV-negative women. HPV 16, 35, and 58 were the most common
      high-risk HPV types with no major differences in the type distribution by HIV
      status. HPV 18 was more common in older HIV-positive women (40-65 years) with no
      or low grade disease, but less common in younger women (17-29 years) with CIN 2
      or 3 compared to HIV-negative counterparts (p < 0.03). Infections with multiple
      high-risk HPV types were more common in HIV-positive than HIV-negative women,
      controlling for age and cervical disease status. CONCLUSION: HIV-positive women
      were more likely to have high-risk HPV than HIV-negative women; but, among those
      with HPV, the distribution of HPV types was similar by HIV status. Screening
      strategies incorporating HPV genotyping and vaccination should be effective in
      preventing cervical cancer in both HIV-positive and -negative women living in sub
      Saharan Africa.

PMID- 24672771
TI  - Oncogenic micro-RNAs and Renal Cell Carcinoma.
AB  - Tumor formation is a complex process that occurs in different steps and involves
      many cell types, including tumor cells, endothelial cells, and inflammatory
      cells, which interact to promote growth of the tumor mass and metastasization.
      Epigenetic alterations occurring in transformed cells result in de-regulation of
      miRNA expression (a class of small non-coding RNA that regulates multiple
      functions), which contributes to tumorigenesis. The specific miRNAs, which have
      an aberrant expression in tumors, are defined as oncomiRNAs, and may be either
      over- or under-expressed, but down-regulation is most commonly observed. Renal
      cell carcinoma (RCC) is a frequent form of urologic tumor, associated with an
      alteration of multiple signaling pathways. Many molecules involved in the
      progression of RCCs, such as HIF, VEGF, or mammalian target of rapamycin, are
      possible targets of de-regulated miRNAs. Within tumor mass, the cancer stem cell
      (CSC) population is a fundamental component that promotes tumor growth. The CSC
      hypothesis postulates that CSCs have the unique ability to self-renew and to
      maintain tumor growth and metastasis. CSCs present in RCC were shown to express
      the mesenchymal stem cell marker CD105 and to exhibit self-renewal and clonogenic
      properties, as well as the ability to generate serially transplantable tumors.
      The phenotype of CSC has been related to the potential to undergo the epithelial
      mesenchymal transition, which has been linked to the expression pattern of
      tumorigenic miRNAs or down-regulation of anti-tumor miRNAs. In addition, the
      pattern of circulating miRNAs may allow discrimination between healthy and tumor
      patients. Therefore, a miRNA signature may be used as a tumor biomarker for
      cancer diagnosis, as well as to classify the risk of relapse and metastasis, and
      for a guide for therapy. 

PMID- 24672772
TI  - The Pasteur's Dictum: Nitrogen Promotes Growth and Oxygen Reduces the Need for
      Sugar.

PMID- 24672773
TI  - Biological Rationale for the Use of PPARgamma Agonists in Glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common primary intrinsic central
      nervous system tumor and has an extremely poor overall survival with only 10%
      patients being alive after 5 years. There has been interesting preliminary
      evidence suggesting that diabetic patients receiving peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists, a group of anti-diabetic,
      thiazolidinedione drugs, have an increased median survival for glioblastoma.
      Although thiazolidinediones are effective oral medications for type 2 diabetes,
      certain agonists carry the risk for congestive heart failure, myocardial
      infarction, cardiovascular disease, bone loss, weight gain, and fluid retention
      as side-effects. The nuclear receptor transcription factor PPARgamma has been
      found to be expressed in high grade gliomas, and its activation has been shown to
      have several antineoplastic effects on human and rat glioma cell lines, and in
      some instances an additional protective increase in antioxidant enzymes has been
      observed in normal astrocytes. At present, no clinical trials are underway with
      regards to treating glioma patients using PPARgamma agonists. This review
      presents the case for evaluating the potential of PPARgamma agonists as novel
      adjuvants in the treatment of refractory high grade glioma. 

PMID- 24672774
TI  - A new spontaneously transformed syngeneic model of high-grade serous ovarian
      cancer with a tumor-initiating cell population.
AB  - Improving screening and treatment options for patients with epithelial ovarian
      cancer has been a major challenge in cancer research. Development of novel
      diagnostic and therapeutic approaches, particularly for the most common subtype,
      high-grade serous ovarian cancer (HGSC), has been hampered by controversies over
      the origin of the disease and a lack of spontaneous HGSC models to resolve this
      controversy. Over long-term culture in our laboratory, an ovarian surface
      epithelial (OSE) cell line spontaneously transformed OSE (STOSE). The objective
      of this study was to determine if the STOSE cell line is a good model of HGSC.
      STOSE cells grow faster than early passage parental M0505 cells with a doubling
      time of 13 and 48 h, respectively. STOSE cells form colonies in soft agar, an
      activity for which M0505 cells have negligible capacity. Microarray analysis
      identified 1755 down-regulated genes and 1203 up-regulated genes in STOSE
      compared to M0505 cells, many associated with aberrant Wnt/beta-catenin and Nf
      kappaB signaling. Upregulation of Ccnd1 and loss of Cdkn2a in STOSE tumors is
      consistent with changes identified in human ovarian cancers by The Cancer Genome
      Atlas. Intraperitoneal injection of STOSE cells into severe combined
      immunodeficient and syngeneic FVB/N mice produced cytokeratin+, WT1+, inhibin-,
      and PAX8+ tumors, a histotype resembling human HGSC. Based on evidence that a
      SCA1+ stem cell-like population exists in M0505 cells, we examined a
      subpopulation of SCA1+ cells that is present in STOSE cells. Compared to SCA1-
      cells, SCA1+ STOSE cells have increased colony-forming capacity and form palpable
      tumors 8 days faster after intrabursal injection into FVB/N mice. This study has
      identified the STOSE cells as the first spontaneous murine model of HGSC and
      provides evidence for the OSE as a possible origin of HGSC. Furthermore, this
      model provides a novel opportunity to study how normal stem-like OSE cells may
      transform into tumor-initiating cells. 

PMID- 24672776
TI  - A new dye uptake assay to test the activity of antibiotics against intracellular
      Francisella tularensis.
AB  - Francisella tularensis, a facultative intracellular bacterium, is the
      aetiological agent of tularaemia. Antibiotic treatment of this zoonosis is based
      on the administration of a fluoroquinolone or a tetracycline for cases with mild
      to moderate severity, whereas an aminoglycoside (streptomycin or gentamicin) is
      advocated for severe cases. However, treatment failures and relapses remain
      frequent, especially in patients suffering from chronic lymph node suppuration.
      Therefore, new treatment alternatives are needed. We have developed a dye uptake
      assay for determination of minimal inhibitory extracellular concentrations
      (MIECs) of antibiotics against intracellular F. tularensis, and validated the
      method by comparing the results obtained using a CFU-enumerating method. We also
      compared MIECs with MICs of the same compounds determined using a CLSI broth
      microdilution method. We tested the activity of 11 antibiotics against two
      clinical strains of F. tularensis subsp. holarctica isolated in France. Both
      strains displayed low MICs (<=1 MUg/mL) to fluoroquinolones (ciprofloxacin,
      levofloxacin and moxifloxacin), gentamicin, doxycycline and rifampicin. Higher
      MICs (>=8 MUg/mL) were found for carbapenems (imipenem and meropenem), daptomycin
      and linezolid. Erythromycin MICs were 4.0 and 16.0 MUg/mL, respectively, for the
      two clinical strains. MIECs were almost the same with the two methods used. They
      were concordant with MICs, except for erythromycin and linezolid (respectively,
      four and eight times more active against intracellular F. tularensis) and
      gentamicin (four to eight times less active against intracellular F. tularensis).
      This study validated the dye uptake assay as a new tool for determination of the
      activity of a large panel of antibiotics against intracellular F. tularensis.
      This test confirmed the intracellular activity of first-line antibiotics used for
      tularaemia treatment, but also revealed significant activity of linezolid against
      intracellular F. tularensis. 

PMID- 24672775
TI  - Molecular therapeutic approaches for pediatric acute myeloid leukemia.
AB  - Approximately two-thirds of children with acute myeloid leukemia (AML) are cured
      with intensive multi-agent chemotherapy. However, refractory and relapsed AML
      remains a significant source of childhood cancer mortality, highlighting the need
      for new therapies. Further therapy intensification with traditional cytotoxic
      chemotherapy in pediatric AML is not feasible given the risks of both short-term
      and long-term organ dysfunction. Substantial emphasis has been placed upon the
      development of molecularly targeted therapeutic approaches for adults and
      children with high-risk subtypes of AML with the goal of improving remission
      induction and minimizing relapse. Several promising agents are currently in
      clinical testing or late preclinical development for AML, including monoclonal
      antibodies against leukemia cell surface proteins, kinase inhibitors, proteasome
      inhibitors, epigenetic agents, and chimeric antigen receptor engineered T cell
      immunotherapies. Many of these therapies have been specifically tested in
      children with relapsed/refractory AML in Phase 1 and 2 trials with a smaller
      number of new agents under Phase 3 evaluation for children with de novo AML.
      Although successful identification and implementation of new drugs for children
      with AML remain a formidable challenge, enthusiasm for novel molecular
      therapeutic approaches is great given the potential for significant clinical
      benefit for children who do not have other curative options. 

PMID- 24672777
TI  - Cytokeratin 18 is not required for morphogenesis of developing prostates but
      contributes to adult prostate regeneration.
AB  - Cytokeratin 18 (CK18) is a key component of keratin-containing intermediate
      filaments and has long been used as a classic luminal cell marker in prostatic
      tissue. However, the in vivo function of CK18 in prostate is not known so far. We
      reported in this study, unexpectedly, that deletion of CK18 in a mouse model did
      not affect the morphological or the histological structures of adult prostate, as
      the CK18 knockout prostate displayed a normal glandular ductal structure,
      branching pattern, and composition of both luminal and basal cells. However, CK18
      loss compromised the regenerative tubular branching in dorsolateral prostate
      after castration and androgen replacement. Therefore, in contrast to its
      importance as luminal cell marker, CK18 is dispensable for the prostate
      morphogenesis but contributes to adult prostate regeneration. 

PMID- 24672779
TI  - Bioactive natural matrices and compounds.

PMID- 24672778
TI  - Stress hormone and reproductive system in response to honey supplementation
      combined with different jumping exercise intensities in female rats.
AB  - This study was performed to determine the effects of 8-week honey supplementation
      combined with different jumping exercise intensities on serum cortisol,
      progesterone, estradiol, and reproductive organs. Eighty-four 9-week-old female
      rats were divided into 7 groups: baseline controls (C0), sedentary group (C), 20
      and 80 jumps per day (Ex(20J), Ex(80J)), honey (H), and combined honey with 20
      and 80 jumps per day (HEx(20J), HEx(80J)) groups. Jumping exercise was performed
      at 5 days/week and honey was given at a dosage of 1 g/kg body weight/day for 7
      days/week. The level of serum cortisol was higher in Ex(20J) and Ex(80J) compared
      to C. There was significantly lower value of serum cortisol in HEx(20J) compared
      to Ex(80J). Serum progesterone levels were significantly lower in Ex(20J) and
      Ex(80J) compared to C. However, serum progesterone levels were significantly
      higher in HEx(20J) and HEx(80J) compared to Ex(20J) and Ex(80J). Relative uterine
      weights were significantly greater in HEx(20J) compared to C and HEx(80J),
      respectively. There was no significant difference in estradiol level and relative
      ovarian weights among all the groups. Therefore, honey elicited beneficial
      effects in reducing the increase of cortisol and in increasing the reduce of
      progesterone levels induced by different intensities jumping exercise in female
      rats.

PMID- 24672780
TI  - Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance
      endogenous neurogenesis in an ischemic stroke model.
AB  - Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate
      neurological deficits in ischemic stroke models. Among the various hypotheses
      that have been suggested to explain the therapeutic mechanism underlying these
      observations, neurogenesis is thought to be critical. To enhance the therapeutic
      benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified
      hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via
      adenoviral transduction mediated by cell-permeable peptides and investigated
      whether BDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and
      endogenous neurogenesis in a rat model of middle cerebral artery occlusion
      (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2'
      deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation
      of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more
      significantly, while suppressing cell death. Newborn cells differentiated into
      doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive
      mature neurons in the subventricular zone and ischemic boundary at higher rates
      in animals with MSCs-BDNF compared with treatment using solely phosphate buffered
      saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral
      analysis revealed greater functional recovery in animals with MSCs-BDNF compared
      with the other groups. MSCs-BDNF exhibited effective therapeutic potential by
      protecting cell from apoptotic death and enhancing endogenous neurogenesis. 

PMID- 24672781
TI  - A role for T-lymphocytes in human breast cancer and in canine mammary tumors.
AB  - Chronic inflammation in the tumor microenvironment has a prominent role in
      carcinogenesis and benefits the proliferation and survival of malignant cells,
      promoting angiogenesis and metastasis. Mammary tumors are frequently infiltrated
      by a heterogeneous population of immune cells where T-lymphocytes have a great
      importance. Interestingly, similar inflammatory cell infiltrates, cytokine and
      chemokine expression in humans and canine mammary tumors were recently described.
      However, in both species, despite all the scientific evidences that appoint for a
      significant role of T-lymphocytes, a definitive conclusion concerning the
      effectiveness of T-cell dependent immune mechanisms has not been achieved yet. In
      the present review, we describe similarities between human breast cancer and
      canine mammary tumors regarding tumor T-lymphocyte infiltration, such as
      relationship of TILs and mammary tumors malignancy, association of ratio CD4+/
      CD8+ T-cells with low survival rates, promotion of tumor progression by Th2 cells
      actions, and association of great amounts of Treg cells with poor prognostic
      factors. This apparent parallelism together with the fact that dogs develop
      spontaneous tumors in the context of a natural immune system highlight the dog as
      a possible useful biological model for studies in human breast cancer immunology.

PMID- 24672782
TI  - Evaluating the influence of motor control on selective attention through a
      stochastic model: the paradigm of motor control dysfunction in cerebellar
      patient.
AB  - Attention allows us to selectively process the vast amount of information with
      which we are confronted, prioritizing some aspects of information and ignoring
      others by focusing on a certain location or aspect of the visual scene. Selective
      attention is guided by two cognitive mechanisms: saliency of the image (bottom
      up) and endogenous mechanisms (top down). These two mechanisms interact to direct
      attention and plan eye movements; then, the movement profile is sent to the motor
      system, which must constantly update the command needed to produce the desired
      eye movement. A new approach is described here to study how the eye motor control
      could influence this selection mechanism in clinical behavior: two groups of
      patients (SCA2 and late onset cerebellar ataxia LOCA) with well-known problems of
      motor control were studied; patients performed a cognitively demanding task; the
      results were compared to a stochastic model based on Monte Carlo simulations and
      a group of healthy subjects. The analytical procedure evaluated some energy
      functions for understanding the process. The implemented model suggested that
      patients performed an optimal visual search, reducing intrinsic noise sources.
      Our findings theorize a strict correlation between the "optimal motor system" and
      the "optimal stimulus encoders." 

PMID- 24672783
TI  - Genetic diversity and distribution of human norovirus in China (1999-2011).
AB  - Noroviruses (NoVs) are a leading cause of epidemic and sporadic acute
      gastroenteritis worldwide. However, the genetic diversity and geographical
      distribution of NoV isolates from China have not been well described thus far. In
      this study, all NoV sequences obtained in China from 1999 to 2011 (n = 983), both
      partial and complete genomes, were downloaded from GenBank. Genotyping and
      phylogenetic and recombination analyses were performed in order to gain a better
      understanding of the distribution and genetic diversity of NoVs in China. The
      results indicated that approximately 90% of NoV sequences were obtained from the
      coastal regions of China, and most of the NoV sequences from distinct
      geographical regions appeared to be closely related. GII.4 was the most prevalent
      genotype, accounting for 64.4% of all genotypes, followed by GII.12 (13.9%) and
      GII.3 (7.0%). Over the last decade, the GII.4 variants were dominated by
      successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008,
      with GII.4/2006b continuing to date. A relatively high frequency of NoV
      intergenotype recombinants was identified. The most common ORF1/ORF2
      intergenotype recombinant was GII.12/GII.4 (n = 11), and the relative frequency
      was up to 30% among all the recombinant strains (n = 36). These findings may aid
      in the evaluation and implementation of appropriate measures for monitoring NoV
      infectious diseases in China. 

PMID- 24672787
TI  - Automated identification of dementia using FDG-PET imaging.
AB  - Parametric FDG-PET images offer the potential for automated identification of the
      different dementia syndromes. However, various existing image features and
      classifiers have their limitations in characterizing and differentiating the
      patterns of this disease. We reported a hybrid feature extraction, selection, and
      classification approach, namely, the GA-MKL algorithm, for separating patients
      with suspected Alzheimer's disease and frontotemporal dementia from normal
      controls. In this approach, we extracted three groups of features to describe the
      average level, spatial variation, and asymmetry of glucose metabolic rates in 116
      cortical volumes. An optimal combination of features, that is, capable of
      classifying dementia cases was identified by a genetic algorithm- (GA-) based
      method. The condition of each FDG-PET study was predicted by applying the
      selected features to a multikernel learning (MKL) machine, in which the weighting
      parameter of each kernel function can be automatically estimated. We compared our
      approach to two state-of-the-art dementia identification algorithms on a set of
      129 clinical cases and improved the performance in separating the dementia types,
      achieving accuracy of 94.62%. There is a very good agreement between the proposed
      automated technique and the diagnosis made by clinicians. 

PMID- 24672784
TI  - Thymic epithelial cell development and its dysfunction in human diseases.
AB  - Thymic epithelial cells (TECs) are the key components in thymic microenvironment
      for T cells development. TECs, composed of cortical and medullary TECs, are
      derived from a common bipotent progenitor and undergo a stepwise development
      controlled by multiple levels of signals to be functionally mature for supporting
      thymocyte development. Tumor necrosis factor receptor (TNFR) family members
      including the receptor activator for NF kappa B (RANK), CD40, and lymphotoxin
      beta receptor (LT beta R) cooperatively control the thymic medullary
      microenvironment and self-tolerance establishment. In addition, fibroblast growth
      factors (FGFs), Wnt, and Notch signals are essential for establishment of
      functional thymic microenvironment. Transcription factors Foxn1 and autoimmune
      regulator (Aire) are powerful modulators of TEC development, differentiation, and
      self-tolerance. Dysfunction in thymic microenvironment including defects of TEC
      and thymocyte development would cause physiological disorders such as tumor,
      infectious diseases, and autoimmune diseases. In the present review, we will
      summarize our current understanding on TEC development and the underlying
      molecular signals pathways and the involvement of thymus dysfunction in human
      diseases. 

PMID- 24672785
TI  - Evaluation of Bax and Bak gene mutations and expression in breast cancer.
AB  - Genetic analyses have provided evidence to suggest that Bax and Bak are the
      essential genes for apoptosis in mammalians cells. This study aimed to search for
      biomarkers in breast cancer to be used as prognostic markers for the disease. The
      Bak and Bax genes expressions were analyzed in 23 breast cancer patients by RT
      PCR technique. SSCP technique was used to detect the mobility of the abnormal
      fragment in Bak exon 4. PCR for Bax promoter was digested with Tau 1 restriction
      enzyme to identify a single polymorphism G(-248)A. The expression of Bak gene is
      related to several clinical factors of breast cancer. The analysis of Bax RNA
      showed 4 isoforms of Bax with different distributions in the normal and tumor
      tissues. These isoforms were Bax alpha , d, delta , and zeta . Exon 4 had a
      normal pattern in all cases of breast cancer. There was a statistically
      significant difference in the frequency distribution of the G(-248)A genotypes in
      the breast cancer tissues with grade 3+high, T2 stage, lobular +other, and PR -ve
      subgroups. In this study, Bak expression seems to lead to development of breast
      cancer and affects the disease progression. Also, Bax d and Bax delta could be
      used as risk factor and biomarker for breast cancer with the distribution of
      G284A. 

PMID- 24672788
TI  - Effect of temperature on Chinese rice wine brewing with high concentration
      presteamed whole sticky rice.
AB  - Production of high quality Chinese rice wine largely depends on fermentation
      temperature. However, there is no report on the ethanol, sugars, and acids
      kinetics in the fermentation mash of Chinese rice wine treated at various
      temperatures. The effects of fermentation temperatures on Chinese rice wine
      quality were investigated. The compositions and concentrations of ethanol,
      sugars, glycerol, and organic acids in the mash of Chinese rice wine samples were
      determined by HPLC method. The highest ethanol concentration and the highest
      glycerol concentration both were attained at the fermentation mash treated at 23 
      degrees C. The highest peak value of maltose (90 g/L) was obtained at 18  degrees
      C. Lactic acid and acetic acid both achieved maximum values at 33  degrees C. The
      experimental results indicated that temperature contributed significantly to the
      ethanol production, acid flavor contents, and sugar contents in the fermentation
      broth of the Chinese rice wines.

PMID- 24672789
TI  - Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin,
      prostaglandins, and amino acids.
AB  - Esophagitis was induced in rats within 3 h by ligating both the pylorus and
      transitional region between the forestomach and glandular portion under ether
      anesthesia. This esophageal injury was prevented by the administration of acid
      suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was
      also aggravated by pretreatment with indomethacin and the selective COX-1 but not
      COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a
      protection at low doses, and an aggravation at high doses, with both being
      mediated by EP1 receptors. Various amino acids also affected this esophagitis in
      different ways; L-alanine and L-glutamine had a deleterious effect, while L
      arginine and glycine were highly protective, both due to yet unidentified
      mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this
      model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of
      the esophagus; and some amino acids are protective against esophagitis. These
      findings also suggest a novel therapeutic approach in the treatment of
      esophagitis, in addition to acid suppressant therapy. The model introduced may be
      useful to test the protective effects of drugs on esophagitis and investigate the
      mucosal defense mechanism in the esophagus.

PMID- 24672791
TI  - Fluid consumption by Mexican women during pregnancy and first semester of
      lactation.
AB  - The objective of this study was to describe daily fluid consumption in a sample
      of pregnant or lactating adult women. Women between 18 and 45 years of age,
      residents of Mexico City, stratified by socioeconomic status were asked to
      register their total fluid intake during 7 consecutive days. A total of 153
      pregnant and 155 lactating women were recruited. On average, they drank 2.62
      L/day and 2.75 L/day, respectively. Forty-one percent of pregnant women drank
      less than the recommended 2.3 L fluids/day, and 54% of women drank less than the
      recommended intake of 2.7 L/day during the first semester of lactation. Plain
      water contributed to 33% of total fluid intake, and sugar-sweetened beverages
      (SSB) contributed to 38% of total fluid intake. Up to 50% of pregnant and
      lactating women drank more than 1 L/day of SSB, which contributed to 632 kcal/day
      (27.5% of recommended dietary intake) and to 700 kcal/day (28% of recommended
      dietary intake), respectively. The high rates of overweight and obesity found in
      Mexican population, particularly among women, should alert us to the consumption
      of SSB during pregnancy and lactation, as excessive intake of these beverages may
      increase the risks of obesity, diabetes mellitus, and other chronic disorders.

PMID- 24672792
TI  - Endoscopic and pathologic changes of the upper gastrointestinal tract in Crohn's
      disease.
AB  - BACKGROUND: Crohn's disease (CD) may involve any part of the gastrointestinal
      tract. We assessed the prevalence and features of upper gastrointestinal (UGI)
      lesions in CD. METHODS: This was a retrospective study that included 138 CD
      patients that underwent esophagogastroduodenoscopy (EGD). The rate of Crohn's
      specific endoscopic lesions in the esophagus, stomach, and duodenum was assessed,
      and immunohistochemical analysis was performed. Changes in the UGI lesions were
      assessed in those who had two or more EGD. RESULTS: Of 138 patients, 51.3% had
      Crohn's specific UGI lesions. The rates of Crohn's specific lesion in the
      esophagus, upper-to-middle stomach, lower stomach, duodenal bulb, and 2nd portion
      of the duodenum were 6.5%, 47.8%, 24.6%, 31.9%, and 18.1%, respectively.
      Granulomas were detected in 6.1%, 25.0%, and 11.4% in the upper-to-middle
      stomach, lower stomach, and duodenal bulb, respectively, but none in the
      esophagus and 2nd portion of the duodenum. Thirty-seven were analyzed for
      Helicobacter pylori and 4 were positive (10.8%). Improvements of UGI lesions were
      seen in 14 out of 49 (28.5%) and were unchanged in 59.2% and worsened in 12.2%.
      CONCLUSIONS: The prevalence of Crohn's specific UGI lesions was common in our
      case series, and immunohistochemical studies suggested that the majority was
      unrelated to Helicobacter pylori infection. Worsening of UGI lesions over the
      course was rare.

PMID- 24672793
TI  - Use of synthetic single-stranded oligonucleotides as artificial test soiling for
      validation of surgical instrument cleaning processes.
AB  - Surgical instruments are often strongly contaminated with patients' blood and
      tissues, possibly containing pathogens. The reuse of contaminated instruments
      without adequate cleaning and sterilization can cause postoperative inflammation
      and the transmission of infectious diseases from one patient to another. Thus,
      based on the stringent sterility requirements, the development of highly
      efficient, validated cleaning processes is necessary. Here, we use for the first
      time synthetic single-stranded DNA (ssDNA_ODN), which does not appear in nature,
      as a test soiling to evaluate the cleaning efficiency of routine washing
      processes. Stainless steel test objects were coated with a certain amount of
      ssDNA_ODN. After cleaning, the amount of residual ssDNA_ODN on the test objects
      was determined using quantitative real-time PCR. The established method is highly
      specific and sensitive, with a detection limit of 20 fg, and enables the
      determination of the cleaning efficiency of medical cleaning processes under
      different conditions to obtain optimal settings for the effective cleaning and
      sterilization of instruments. The use of this highly sensitive method for the
      validation of cleaning processes can prevent, to a significant extent, the
      insufficient cleaning of surgical instruments and thus the transmission of
      pathogens to patients.

PMID- 24672795
TI  - Immediate care of open extremity fractures: where can we improve?
AB  - Clear guidelines are set by the British Orthopaedic Association (BOA) and British
      Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) on the
      preoperative management of open fractures. This as well as the clinical
      consequences of poor management of open fractures means the patient workup for
      surgery is important as well as the timing of surgery. Experience suggests few
      patients are managed 100% as per the guidelines and we look to test this
      hypothesis. A retrospective analysis was undertaken of all open long bone
      fractures (total 133), excluding hand injuries, which presented to a district
      general hospital over a 5-year period. The implementation of 7 defined key tasks
      for initial management was recorded. 101 cases were eligible, with the majority
      of cases (71.4%) having initial orthopaedic assessment outside normal working
      hours. The mean number of tasks completed was 3.23/7. Assessment out of hours was
      associated with less tasks being implemented but doctor seniority and the
      presence of polytrauma made no difference to the quality of acute care. Staff
      involved in the acute care of open fractures require targeted education to
      improve the delivery of initial preoperative care. We recommend that other
      centres assess their performance against this data. 

PMID- 24672794
TI  - The role of bioactive lipids in stem cell mobilization and homing: novel
      therapeutics for myocardial ischemia.
AB  - Despite significant advances in medical therapy and interventional strategies,
      the prognosis of millions of patients with acute myocardial infarction (AMI) and
      ischemic heart disease (IHD) remains poor. Currently, short of heart
      transplantation with all of its inherit limitations, there are no available
      treatment strategies that replace the infarcted myocardium. It is now well
      established that cardiomyocytes undergo continuous renewal, with contribution
      from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is
      upregulated during AMI by initiating multiple innate reparatory mechanisms
      through which BMSPCs are mobilized towards the ischemic myocardium and contribute
      to myocardial regeneration. While a role for the SDF-1/CXCR4 axis in retention of
      BMSPCs in bone marrow is undisputed, its exclusive role in their mobilization and
      homing to a highly proteolytic microenvironment, such as the ischemic/infarcted
      myocardium, is currently being challenged. Recent evidence suggests a pivotal
      role for bioactive lipids in the mobilization of BMSPCs at the early stages
      following AMI and their homing towards ischemic myocardium. This review
      highlights the recent advances in our understanding of the mechanisms of stem
      cell mobilization, provides newer evidence implicating bioactive lipids in BMSPC
      mobilization and differentiation, and discusses their potential as therapeutic
      agents in the treatment of IHD. 

PMID- 24672797
TI  - Effects of Momordica charantia L. on the blood rheological properties in diabetic
      patients.
AB  - An evaluation of the rheological properties and the effects of Momordica.
      charantia L. (M. charantia) nanoparticles and polyethylene glycol (PEG)
      microspheres adsorbed with M. charantia nanoparticles on the blood of
      hyperglycemic patients is presented. Blood samples were collected according to
      glycemic status: normoglycemic (N = 56) and hyperglycemic (N = 26). General and
      hematological characteristics were determined. Blood rheological parameters were
      determined at room temperature and under a temperature scan. We determined the
      effects on whole blood viscosity of treatment with an extract of M. charantia,
      PEG, or PEG microspheres adsorbed with plant extract. The viscosity of the blood
      of hyperglycemic patients is greater than that of normoglycemic patients.
      Nanoparticles of M. charantia extracts lowered blood viscosity at equivalent
      rates in normo- and hyperglycemic individuals. PEG microspheres did not reduce
      blood viscosity in hyperglycemic individuals. However, PEG microspheres adsorbed
      with nanofraction extracts of M. charantia reduced blood viscosity. These data
      suggest that the effects of diabetes on the viscosity of the blood should be
      considered. The use of a nanoparticles extract of M. charantia and its adsorption
      on PEG microspheres may represent an alternative for the control and treatment of
      blood disorders in diabetic patients. 

PMID- 24672798
TI  - Characteristics, process parameters, and inner components of anaerobic
      bioreactors.
AB  - The anaerobic bioreactor applies the principles of biotechnology and
      microbiology, and nowadays it has been used widely in the wastewater treatment
      plants due to their high efficiency, low energy use, and green energy generation.
      Advantages and disadvantages of anaerobic process were shown, and three main
      characteristics of anaerobic bioreactor (AB), namely, inhomogeneous system, time
      instability, and space instability were also discussed in this work. For high
      efficiency of wastewater treatment, the process parameters of anaerobic
      digestion, such as temperature, pH, Hydraulic retention time (HRT), Organic
      Loading Rate (OLR), and sludge retention time (SRT) were introduced to take into
      account the optimum conditions for living, growth, and multiplication of
      bacteria. The inner components, which can improve SRT, and even enhance mass
      transfer, were also explained and have been divided into transverse inner
      components, longitudinal inner components, and biofilm-packing material. At last,
      the newly developed special inner components were discussed and found more
      efficient and productive. 

PMID- 24672799
TI  - Semiphysiological versus empirical modelling of the population pharmacokinetics
      of free and total cefazolin during pregnancy.
AB  - This work describes a first population pharmacokinetic (PK) model for free and
      total cefazolin during pregnancy, which can be used for dose regimen
      optimization. Secondly, analysis of PK studies in pregnant patients is
      challenging due to study design limitations. We therefore developed a
      semiphysiological modeling approach, which leveraged gestation-induced changes in
      creatinine clearance (CrCL) into a population PK model. This model was then
      compared to the conventional empirical covariate model. First, a base two
      compartmental PK model with a linear protein binding was developed. The empirical
      covariate model for gestational changes consisted of a linear relationship
      between CL and gestational age. The semiphysiological model was based on the base
      population PK model and a separately developed mixed-effect model for gestation
      induced change in CrCL. Estimates for baseline clearance (CL) were 0.119 L/min
      (RSE 58%) and 0.142 L/min (RSE 44%) for the empirical and semiphysiological
      models, respectively. Both models described the available PK data comparably
      well. However, as the semiphysiological model was based on prior knowledge of
      gestation-induced changes in renal function, this model may have improved
      predictive performance. This work demonstrates how a hybrid semiphysiological
      population PK approach may be of relevance in order to derive more informative
      inferences.

PMID- 24672800
TI  - The role of PinX1 in growth control of breast cancer cells and its potential
      molecular mechanism by mRNA and lncRNA expression profiles screening.
AB  - As a major tumor suppressor gene, the role of PinX1 in breast cancer and its
      molecular mechanism remain unclear. In this study, overexpression of PinX1 was
      generated in 3 breast cancer cell lines, and knockdown of PinX1 was performed in
      a nontumorigenic breast cell line. The regulation of PinX1 on cell proliferation
      and cell cycle was observed. A microarray-based lncRNA and mRNA expression
      profile screening was also performed. We found a lower growth rate, G0/G1 phase
      arrest, and S phase inhibition in the PinX1 overexpressed breast cancer cells,
      while a higher growth rate, decreased G0/G1 phase, and increased S phase rate in
      the PinX1 knocked-down nontumorigenic breast cell. A total of 977 mRNAs and 631
      lncRNAs were identified as differentially expressed transcripts between PinX1
      overexpressed and control MCF-7 cells. Further analysis identified the
      involvement of these mRNAs in 52 cancer related pathways and various other
      biological processes. 11 enhancer-like lncRNAs and 25 lincRNAs with their
      adjacent mRNA pairs were identified as coregulated transcripts. Our results
      confirmed the role of PinX1 as a major tumor suppressor gene in breast cancer
      cell lines and provided information for further research on the molecular
      mechanisms of PinX1 in tumorigenesis. 

PMID- 24672801
TI  - A replication study for the association of rs726252 in PAPPA2 with developmental
      dysplasia of the hip in Chinese Han population.
AB  - Developmental dysplasia of the hip (DDH) is a common developmental hip disorder,
      which ranges from mild acetabulum malformation to irreducible hip dislocation. A
      previous study suggested a significant association of pregnancy-associated plasma
      protein-A2 (PAPPA2) with DDH susceptibility in Chinese Han population. But with
      the consideration of the sample size, the association was still debatable. To
      confirm the association of the reported single nucleotide polymorphism (SNP) in
      PAPPA2, rs726252 with DDH, we conducted a case-control study in a larger number
      of subjects. We genotyped rs726252 in 697 DDH subjects and 707 control subjects
      by TaqMan assay. The association between this SNP and DDH was evaluated
      statistically. No significant difference was found in any comparison of genotype
      distribution nor allele frequency between cases and controls. Our replication
      study indicated that the association between rs726252 and DDH in Chinese Han
      population was debatable. The association between PAPPA2 and DDH should be
      evaluated by additional studies. 

PMID- 24672796
TI  - Targeted delivery system of nanobiomaterials in anticancer therapy: from cells to
      clinics.
AB  - Targeted delivery systems of nanobiomaterials are necessary to be developed for
      the diagnosis and treatment of cancer. Nanobiomaterials can be engineered to
      recognize cancer-specific receptors at the cellular levels and to deliver
      anticancer drugs into the diseased sites. In particular, nanobiomaterial-based
      nanocarriers, so-called nanoplatforms, are the design of the targeted delivery
      systems such as liposomes, polymeric nanoparticles/micelles, nanoconjugates,
      norganic materials, carbon-based nanobiomaterials, and bioinspired phage system,
      which are based on the nanosize of 1-100 nm in diameter. In this review, the
      design and the application of these nanoplatforms are discussed at the cellular
      levels as well as in the clinics. We believe that this review can offer recent
      advances in the targeted delivery systems of nanobiomaterials regarding in vitro
      and in vivo applications and the translation of nanobiomaterials to nanomedicine
      in anticancer therapy.

PMID- 24672802
TI  - Adipocytes from New Zealand obese mice exhibit aberrant proinflammatory
      reactivity to the stress signal heat shock protein 60.
AB  - Adipocytes release immune mediators that contribute to diabetes-associated
      inflammatory processes. As the stress protein heat shock protein 60 (Hsp60)
      induces proinflammatory adipocyte activities, we hypothesized that adipocytes of
      diabetes-predisposed mice exhibit an increased proinflammatory reactivity to
      Hsp60. Preadipocytes and mature adipocytes from nonobese diabetic (NOD), New
      Zealand obese (NZO), and C57BL/6J mice were analyzed for Hsp60 binding, Hsp60
      activated signaling pathways, and Hsp60-induced release of the chemokine CXCL-1
      (KC), interleukin 6 (IL-6), and macrophage chemoattractant protein-1 (MCP-1).
      Hsp60 showed specific binding to (pre-)adipocytes of NOD, NZO, and C57BL/6J mice.
      Hsp60 binding involved conserved binding structure(s) and Hsp60 epitopes and was
      strongest to NZO mouse-derived mature adipocytes. Hsp60 exposure induced KC, IL
      6, and MCP-1 release from (pre-)adipocytes of all mouse strains with a pronounced
      increase of IL-6 release from NZO mouse-derived adipocytes. Compared to NOD and
      C57BL/6J mouse derived cells, Hsp60-induced formation of IL-6, KC, and MCP-1 from
      NZO mouse-derived (pre-)adipocytes strongly depended on NF kappa B-activation.
      Increased Hsp60 binding and Hsp60-induced IL-6 release by mature adipocytes of
      NZO mice suggest that enhanced adipocyte reactivity to the stress signal Hsp60
      contributes to inflammatory processes underlying diabetes associated with obesity
      and insulin resistance. 

PMID- 24672803
TI  - Impact of bariatric surgery on ghrelin and obestatin levels in obesity or type 2
      diabetes mellitus rat model.
AB  - We aimed to evaluate the therapeutic efficacy on weight control by different
      bariatric surgeries and investigate the ghrelin and obestatin changes after these
      surgeries in obesity and nonobese type 2 diabetes mellitus (T2DM) rats. Obese
      rats were randomly assigned to receive sleeve gastrectomy (SG, n = 8),
      minigastric bypass (MGBP, n = 8), roux-en-Y gastric bypass (RYGBP, n = 8), and
      sham operation (SO, n = 4). Another 4 rats served as control. Besides, Goto
      Kakisaki (GK) rats were also randomly divided into similar groups except for
      total gastrectomy (TG, n = 8) group. The results showed that in obese rats, weigh
      loss in RYGBP group was similar to that in MGBP group but larger than that in SG
      group. Ghrelin significantly increased in RYGB group, but obestatin increased in
      MGBP group. Ghrelin/obestatin ratio significantly decreased in SG group. In GK
      rats, weight loss was most obvious in TG group. Postoperatively, ghrelin was
      significantly increased in MGBP and RYGB groups but decreased in TG group.
      Obestatin also showed an increase in MGBP and RYGB groups. Ghrelin/obestatin in
      TG group decreased significantly. In conclusion, RYGB and MGBP may be more
      suitable for obese rats, but TG may be the best strategy for T2DM rats to control
      weight with different mechanisms. 

PMID- 24672804
TI  - Decompensation of beta-cells in diabetes: when pancreatic beta-cells are on
      ICE(R).
AB  - Insulin production and secretion are temporally regulated. Keeping insulin
      secretion at rest after a rise of glucose prevents exhaustion and ultimately
      failure of beta-cells. Among the mechanisms that reduce beta-cell activity is the
      inducible cAMP early repressor (ICER). ICER is an immediate early gene, which is
      rapidly induced by the cyclic AMP (cAMP) signaling cascade. The seminal function
      of ICER is to negatively regulate the production and secretion of insulin by
      repressing the genes expression. This is part of adaptive response required for
      proper beta-cells function in response to environmental factors. Inappropriate
      induction of ICER accounts for pancreatic beta-cells dysfunction and ultimately
      death elicited by chronic hyperglycemia, fatty acids, and oxidized LDL. This
      review underlines the importance of balancing the negative regulation achieved by
      ICER for preserving beta-cell function and survival in diabetes.

PMID- 24672805
TI  - Role of Ink4a/Arf locus in beta cell mass expansion under physiological and
      pathological conditions.
AB  - The ARF/INK4A (Cdkn2a) locus includes the linked tumour suppressor genes p16INK4a
      and p14ARF (p19ARF in mice) that trigger the antiproliferative activities of both
      RB and p53. With beta cell self-replication being the primary source for new beta
      cell generation in adult animals, the network by which beta cell replication
      could be increased to enhance beta cell mass and function is one of the
      approaches in diabetes research. In this review, we show a general view of the
      regulation points at transcriptional and posttranslational levels of Cdkn2a
      locus. We describe the molecular pathways and functions of Cdkn2a in beta cell
      cycle regulation. Given that aging reveals increased p16Ink4a levels in the
      pancreas that inhibit the proliferation of beta cells and decrease their ability
      to respond to injury, we show the state of the art about the role of this locus
      in beta cell senescence and diabetes development. Additionally, we focus on two
      approaches in beta cell regeneration strategies that rely on Cdkn2a locus
      negative regulation: long noncoding RNAs and betatrophin. 

PMID- 24672806
TI  - Prolyl-hydroxylase 3: Evolving Roles for an Ancient Signaling Protein.
AB  - The ability of cells to sense oxygen is a highly evolved process that facilitates
      adaptations to the local oxygen environment and is critical to energy
      homeostasis. In vertebrates, this process is largely controlled by three
      intracellular prolyl-4-hydroxylases (PHD 1-3). These related enzymes share the
      ability to hydroxylate the hypoxia-inducible transcription factor (HIF), and
      therefore control the transcription of genes involved in metabolism and vascular
      recruitment. However, it is becoming increasingly apparent that proline-4
      hydroxylation controls much more than HIF signaling, with PHD3 emerging as an
      exceptionally unique and functionally diverse PHD isoform. In fact, PHD3-mediated
      hydroxylation has recently been purported to function in such diverse roles as
      sympathetic neuronal and muscle development, sepsis, glycolytic metabolism, and
      cell fate. PHD3 expression is also highly distinct from that of the other PHD
      enzymes, and varies considerably between different cell types and oxygen
      concentrations. This review will examine the evolution of oxygen sensing by the
      HIF-family of PHD enzymes, with a specific focus on complex nature of PHD3
      expression and function in mammalian cells.

PMID- 24672808
TI  - Reflections: neurology and the humanities: fishing in the dark.

PMID- 24672809
TI  - Author response.

PMID- 24672807
TI  - Exploitation of the Macrophage Mannose Receptor (CD206) in Infectious Disease
      Diagnostics and Therapeutics.
AB  - The macrophage mannose receptor (MR, CD206) is a C-type lectin expressed
      predominantly by most tissue macrophages, dendritic cells and specific lymphatic
      or endothelial cells. It functions in endocytosis and phagocytosis, and plays an
      important role in immune homeostasis by scavenging unwanted mannoglycoproteins.
      More attention is being paid to its particularly high expression in tissue
      pathology sites during disease such the tumor microenvironment. The MR recognizes
      a variety of microorganisms by their mannan-coated cell wall, which is exploited
      by adapted intracellular pathogens such as Mycobacterium tuberculosis, for their
      own survival. Despite the continued development of drug delivery technologies,
      the targeting of agents to immune cells, especially macrophages, for effective
      diagnosis and treatment of chronic infectious diseases has not been addressed
      adequately. In this regard, strategies that optimize MR-mediated uptake by
      macrophages in target tissues during infection are becoming an attractive
      approach. We review important progress in this area.

PMID- 24672810
TI  - Responsiveness to reduced dosage of rituximab in Chinese patients with
      neuromyelitis optica.

PMID- 24672811
TI  - Author response.

PMID- 24672812
TI  - Resident rounds: Part III. Calciphylaxis in the setting of non-hemodialysis,
      rapid weight loss, and mixed hyperparathyroidism.

PMID- 24672813
TI  - Evolving antithrombotic strategies in patients with atrial fibrillation
      undergoing percutaneous coronary intervention: results from a survey among US
      cardiologists.
AB  - BACKGROUND: Many patients treated with oral anticoagulants for atrial
      fibrillation undergo percutaneous stent implantation, where dual antiplatelet
      therapy (DAPT) is also recommended. The current evidence to support triple oral
      antithrombotic therapy (TOAT) in these patients is limited, and new strategies
      are being discussed to optimize outcomes. HYPOTHESIS: There will be variation in
      antithrombotic strategies in patients with atrial fibrillation needing stenting.
      METHODS: We surveyed US-based cardiologists serving as clinical investigators in
      academic sites and posted an online "question of the month" on cardiosource.org.
      RESULTS: Seventy-five (10.7%) responses were received to the email survey and 119
      to the online question. Bare-metal stenting (BMS) was a priori preferred over
      drug-eluting stenting (DES) for 50.6% of patients. Only 8.8% of the responders
      chose newer anticoagulants in addition to DAPT as the preferred oral
      anticoagulant. For duration of TOAT, 79.4% of physicians recommended stopping
      DAPT at 1 month when BMS was used in patients presenting without acute coronary
      syndrome (ACS) vs 57.4% in patients with ACS. In patients implanted with a DES,
      73.5% and 76.5% preferred stopping DAPT at 6 to 12 months (no ACS vs ACS,
      respectively). When asked which of the 2 antiplatelet agents they would recommend
      stopping after the above durations, 50% chose to quit aspirin. CONCLUSIONS: The
      survey highlights an interest in the new strategy of dropping aspirin, but the
      lack of concrete evidence triggers undesired diversity in clinical approaches.
      High-quality data on the efficacy and safety of such interventions are needed to
      further consolidate these approaches.

PMID- 24672814
TI  - Addition of N-acetyl cysteine to carvedilol decreases the incidence of acute
      renal injury after cardiac surgery.
AB  - BACKGROUND: Oxidative stress and inflammation during cardiac surgery may be
      associated with acute renal injury (ARI). N-acetyl cysteine (NAC) and carvedilol
      have antioxidant and anti-inflammatory properties. HYPOTHESIS: A combination of
      carvedilol and NAC should decrease the incidence of ARI more than metoprolol or
      carvedilol. METHODS: Patients undergoing cardiac surgery were randomized to
      metoprolol, carvedilol, or carvedilol plus NAC. End points were occurrence of ARI
      and change in preoperative to postoperative peak creatinine levels. RESULTS: ARI
      incidence was lower in the carvedilol plus NAC group compared with the metoprolol
      (21.0% vs 42.1%; P = 0.002) or carvedilol (21.0% vs 38.6%; P = 0.006) groups, but
      was similar between the metoprolol and carvedilol groups (P = 0.62). Preoperative
      and postoperative day 1 creatinine levels were similar among the metoprolol (1.02
      [0.9-1.2] and 1.2 [0.92-1.45]) the carvedilol (1.0 [0.88-1.08] and 1.2 [0.9-1.5])
      and the carvedilol plus NAC groups (1.06 [0.9-1.18] and 1.1 [1.0-1.21] mg/dL; all
      P values >0.05). Postoperative day 3, day 5, and peak creatinine levels were
      lower in the carvedilol plus NAC group (1.11 [1.0-1.23], 1.14 [1.0-1.25] and 1.15
      [1.0-1.25]) as compared with the metoprolol (1.4 [1.3-1.49], 1.3 [1.0-1.54] and
      1.3 [1.0-1.54]) or carvedilol groups (1.2 [1.0-1.52], 1.25 [1.0-1.52] and 1.25
      [1.0-1.55] mg/dL; all P values <0.05), but were similar between the metoprolol
      and carvedilol groups (all P values >0.05). CONCLUSIONS: Combined carvedilol and
      NAC decreased ARI incidence as compared with carvedilol or metoprolol. No
      difference was detected between carvedilol and metoprolol.

PMID- 24672815
TI  - Reply to Joel and Tarrasch: On misreading and shooting the messenger.

PMID- 24672817
TI  - Simplicity: the ultimate sophistication.

PMID- 24672816
TI  - Six-week gait retraining program reduces knee adduction moment, reduces pain, and
      improves function for individuals with medial compartment knee osteoarthritis.

PMID- 24672818
TI  - Author reply: To PMID 23746392.

PMID- 24672819
TI  - [B. Hofmann replies].

PMID- 24672820
TI  - The CEO view of HIT. Provider leaders ruminate on the growing dependency of their
      organizations on health information technology.

PMID- 24672821
TI  - Does 'ACO' stand for 'a cash-flow obstacle'? The march to accountable payment
      models is under way, adding to revenue cycle uncertainty.

PMID- 24672822
TI  - Putting patients in charge. Providers and payers rely on self-service apps to
      make it easier to navigate the perplexing health care environment.

PMID- 24672823
TI  - Patient education: An example of grace.

PMID- 24672830
TI  - Report of the 2013 University of Puerto Rico-MD Anderson Cancer Center Conference
      entitled "Research on cancer epidemiology: risk factors and control in the
      Caribbean basin".

PMID- 24672831
TI  - Surgical correction of an arteriovenous fistula in a ring-tailed lemur (Lemur
      catta).
AB  - A 10-y-old ovariohysterectomized ring-tailed lemur (Lemur catta) was presented
      for exacerbation of respiratory signs. The lemur had a history of multiple
      examinations for various problems, including traumatic lacerations and recurrent
      perivulvar dermatitis. Examination revealed abnormal lung sounds and a femoral
      arteriovenous fistula with a palpable thrill and auscultable bruit in the right
      inguinal area. A diagnosis of congestive heart failure was made on the basis of
      exam findings, radiography, abdominal ultrasonography, and echocardiography. The
      lemur was maintained on furosemide until surgical ligation of the fistula was
      performed. Postoperative examination confirmed successful closure of the fistula
      and resolution of the signs of heart failure. Arteriovenous fistulas are abnormal
      connections between an artery and a vein that bypass the capillary bed. Large
      arteriovenous fistulas may result in decreased peripheral resistance and an
      increase in cardiac output with consequent cardiomegaly and high output heart
      failure. This lemur's high-flow arteriovenous fistula with secondary heart
      failure may have been iatrogenically induced during blood collection by prior
      femoral venipuncture. To our knowledge, this report is the first description of
      an arteriovenous fistula in a prosimian. Successful surgical correction of
      suspected iatrogenic femoral arteriovenous fistulas in a cynomolgus monkey
      (Macaca fascicularis) and a rhesus macaque (Macaca mulatta) have been reported
      previously. Arteriovenous fistula formation should be considered as a rare
      potential complication of venipuncture and as a treatable cause of congestive
      heart failure in lemurs.

PMID- 24672833
TI  - Authors' response.

PMID- 24672832
TI  - Differences in memory development among C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl
      mice after delay and trace fear conditioning.
AB  - Fear-conditioning testing paradigms have been used to study differences in memory
      formation between inbred mouse strains, including numerous mouse models of human
      diseases. In this study, we characterized the conditioned fear memory of 3 inbred
      strains: C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl, obtained from Charles River
      Laboratories. We used 2 training paradigms: delay conditioning, in which an
      unconditional stimulus coterminates with the presentation of a conditional
      stimulus, and trace conditioning, in which the conditional and unconditional
      stimuli are separated by a trace interval. In each paradigm, we evaluated the
      recent (3 d) and remote (25 d) memory of the mice by using a longitudinal design.
      Our results showed that both C57BL/6NCrl and 129S2/SvPasCrl mice developed strong
      and long-lasting context and tone memories in both paradigms, but FVB/NCrl mice
      showed a weaker but nevertheless consistent tone memory after delay training.
      Tone memory in the FVB strain was stronger in male than female mice. The remote
      tone memory of 129S2/SvPasCrl mice diminished after delay training but was stable
      and stronger than that of C57BL/6NCrl mice after trace training. In conclusion,
      both C57BL/6NCrl and 129S2/SvPasCrl mice showed reliable and long-lasting fear
      memory after delay or trace training, with 129 mice showing particularly strong
      tone memory after trace conditioning. The FVB/NCrl strain, especially male mice,
      showed reliable tone fear memory after delay training. Our findings confirm that
      both C57BL/6NCrl and 129S2/SvPasCrl mice develop strong context and tone memory
      in delay and trace fear-conditioning paradigms.

PMID- 24672834
TI  - Acute generalized exanthematous pustulosis due to acetazolamide: negative on
      patch testing and confirmed by delayed-reading intradermal testing.

PMID- 24672835
TI  - [CT and MRI findings in patients with autoimmune pancreatitis].
AB  - OBJECTIVE: To evaluate computed tomography (CT) and magnetic resonance imaging
      (MRI) findings in patients with autoimmune pancreatitis (AIP). METHODS: The
      imaging findings of pancreas and extra-pancreas in 24 patients with AIP were
      retrospectively reviewed. Among them, CT scan was performed in 18 patients, MRI
      in 11, and bGth CT and MRI in 10. RESULTS: The pancreas showed diffuse
      enlargement (25%, 6/24), focal enlargement (37. 5%, 9/24), combined enlargement
      (25%, 6/24) ,and no enlargement (12. 5%, 9/24). Unenhanced CT showed
      hypoattenuation in AIP area (n = 2) . After intravenous injection of contrast
      medium, 17 patients showed abnormal contrast enhancement in the affected
      pancreatic parenchyma, including hypoattenuation during the arterial phase (50%,
      9/18) and hyper attenuation during the delayed phase (94. 4%, 17/18). Precontrast
      MRI showed abnormal signal intense (n =9), including hypointense on T1-weight
      images (T1 WI) (n = 7), hyperintense (n = 7) and hypointense (n = 2) on T2-weight
      images (TIWI). Enhanced MRI demonstrated abnormal contrast enhancement within
      lesions (n = 11), including hypoattenuation during the arterial phase (81. 8%,
      9/11) and good enhancement during the delayed phase (100%, 11111). A capsule-like
      rim was seen around pancreas (37. 5%, 9/24), among which CT detected in 6 out of
      18 patients and MRI found in 7 out of 11 patients.The main pancreatic duct lumen
      within lesions has no visualization (100%, 24/24) and upstream dilation of the
      main pancreatic duct (n = 8) , ranging from 2. 2 to 4. 5 mm(mean 3. 1 0. 47 mm)
      in diameter. Narrowing of the common bile duct was shown in 14 patients.
      Miscellaneous findings were: infiltration of extrapancreatic vein (n = 9) and
      artery (n = 1); mild fluid collection around pancreas (n = 2); pseudocysts (n =
      3). Fourteen patients also presented one or more of the following extrapancreatic
      imaging findings: narrowing of the intra-hepatic bile duct or hilar duct (n = 5);
      thickening of gallbladder wall (n = 5); fibrosis in mesenteric (n = 2), in
      retroperitoneal (n = 2) and in ligamentum teres hepatis (n = 1); renal
      involvement (n = 3); peri-pancreatic or para-aortic lymphadenopathy (n = 10); and
      ulcerative colitis (n = 3). CONCLUSION: AIP display some characteristic CT and
      MRI imaging features: sausage-like change of the pancreas; capsule-like rims
      around lesions; delayed contrast enhancement in the affected pancreatic
      parenchyma; segment or diffuse pancreatic duct stenosis but mild upstream
      dilation and extrapancreatic organs involvement. CT and MRI findings combining
      with serological tests and pancreas biopsy can assist physicians to make accurate
      and timely diagnosis.

PMID- 24672836
TI  - New R3 Report addresses NPSG.06.01.01.

PMID- 24672837
TI  - Approved: Second certification option for nursing care centers.

PMID- 24672838
TI  - Modified: Ventricular assist device destination therapy requirements.

PMID- 24672839
TI  - Approved: Enhancements to primary stroke center requirements.

PMID- 24672840
TI  - Accepted: Revised home health requirements align with CMS.

PMID- 24672841
TI  - High-level disinfection and sterilization: know your process.

PMID- 24672842
TI  - Approved: Revisions to comprehensive stroke center requirements.

PMID- 24672843
TI  - Maintaining medical gas safety.

PMID- 24672844
TI  - Genomics: gearing up for the laboratory of the future.

PMID- 24672845
TI  - Pharmacogenetics and pain management: an opportunity to advance personalized
      patient care.

PMID- 24672847
TI  - Healthcare in the cloud: the opportunity and the challenge.

PMID- 24672846
TI  - Companion diagnostics: an emerging component in personalized medicine.

PMID- 24672848
TI  - Pre-analytical errors: working with manufacturers to help improve quality.

PMID- 24672849
TI  - Alternative nucleic amplification strategies, part 2: LCR and HDA.

PMID- 24672850
TI  - Thromboelastometry: its methodology, application, and benefits.

PMID- 24672851
TI  - Next generation sequencing technologies reveal the tumor-associated somatic
      mutation profile.

PMID- 24672853
TI  - Chemometrics in analytical chemistry workflow.

PMID- 24672854
TI  - Experimental design in analytical chemistry--part I: theory.
AB  - This paper reviews the main concepts of experimental design applicable to the
      optimization of analytical chemistry techniques. The critical steps and tools for
      screening, including Plackett-Burman, factorial and fractional factorial designs,
      and response surface methodology such as central composite, Box-Behnken, and
      Doehlert designs, are discussed. Some useful routines are also presented for
      performing the procedures.

PMID- 24672855
TI  - Experimental design in analytical chemistry--part II: applications.
AB  - This paper reviews the applications of experimental design to optimize some
      analytical chemistry techniques such as extraction, chromatography separation,
      capillary electrophoresis, spectroscopy, and electroanalytical methods.

PMID- 24672856
TI  - Chemometric classification techniques as a tool for solving problems in
      analytical chemistry.
AB  - Supervised pattern recognition (classification) techniques, i.e., the family of
      chemometric methods whose aim is the prediction of a qualitative response on a
      set of samples, represent a very important assortment of tools for solving
      problems in several areas of applied analytical chemistry. This paper describes
      the theory behind the chemometric classification techniques most frequently used
      in analytical chemistry together with some examples of their application to real
      world problems.

PMID- 24672858
TI  - Recent applications of first- and second-order multivariate calibration to
      analytical chemistry.
AB  - This report reviews recent literature on the application of multivariate
      calibration techniques to both first- and second-order data, aimed at the
      analytical determination of analytes of interest or sample properties in a
      variety of industrial, pharmaceutical, food, and environmental samples, including
      examples of process control. The most used data processing tools are briefly
      described, with emphasis on the advantages that can be obtained by applying
      specific combinations of multivariate data and algorithms. The main focus is on
      works devoted to first-order data (i.e., spectra, chromatograms, etc.) combined
      with partial least-squares regression, which has become the standard for this
      type of analytical research. A brief discussion on recent work on second-order
      data and algorithms is also included, as this field is rapidly growing, although
      at present it does not show, the general applicability of the first-order
      counterparts.

PMID- 24672857
TI  - Clustering in analytical chemistry.
AB  - Data clustering plays an important role in the exploratory analysis of analytical
      data, and the use of clustering methods has been acknowledged in different fields
      of science. In this paper, principles of data clustering are presented with a
      direct focus on clustering of analytical data. The role of the clustering process
      in the analytical workflow is underlined, and its potential impact on the
      analytical workflow is emphasized.

PMID- 24672860
TI  - A statistical model for assessing performance standards for quantitative and
      semiquantitative disinfectant test methods.
AB  - A performance standard for a disinfectant test method can be evaluated by
      quantifying the (Type I) pass-error rate for ineffective products and the (Type
      II) fail-error rate for highly effective products. This paper shows how to
      calculate these error rates for test methods where the log reduction in a
      microbial population is used as a measure of antimicrobial efficacy. The
      calculations can be used to assess performance standards that may require
      multiple tests of multiple microbes at multiple laboratories. Notably, the error
      rates account for among-laboratory variance of the log reductions estimated from
      a multilaboratory data set and the correlation among tests of different microbes
      conducted in the same laboratory. Performance standards that require that a
      disinfectant product pass all tests or multiple tests on average, are considered.
      The proposed statistical methodology is flexible and allows for a different
      acceptable outcome for each microbe tested, since, for example, variability may
      be different for different microbes. The approach can also be applied to
      semiquantitative methods for which product efficacy is reported as the number of
      positive carriers out of a treated set and the density of the microbes on control
      carriers is quantified, thereby allowing a log reduction to be calculated.
      Therefore, using the approach described in this paper, the error rates can also
      be calculated for semiquantitative method performance standards specified solely
      in terms of the maximum allowable number of positive carriers per test. The
      calculations are demonstrated in a case study of the current performance standard
      for the semiquantitative AOAC Use-Dilution Methods for Pseudomonas aeruginosa
      (964.02) and Staphylococcus aureus (955.15), which allow up to one positive
      carrier out of a set of 60 inoculated and treated carriers in each test. A
      simulation study was also conducted to verify the validity of the model's
      assumptions and accuracy. Our approach, easily implemented using the computer
      code provided, offers a quantitative decision-making tool for assessing a
      performance standard for any disinfectant test method for which log reductions
      can be calculated.

PMID- 24672859
TI  - Variations in the contents of gingerols and chromatographic fingerprints of
      ginger root extracts prepared by different preparation methods.
AB  - In the present study, an HPLC-DAD method was optimized for the quantitative
      determination of 6-gingerol, 6-shogaol, 8-gingerol, and 10-gingerol in ginger
      extracts. A chromatographic fingerprinting method was also established to
      differentiate and evaluate the ginger extracts for bioactivity. Twenty-one
      extracts were prepared by methods differing in ginger type (fresh versus dried),
      solvent, and extraction methods. The ANOVA analysis showed the methods' influence
      on the mean extraction yields of gingerols increased in the order of: high
      pressure-high temperature (HP)>blender (BD)>low pressure (LP). The optimal
      solvent to extract gingerols was found to be 95% ethanol. The type of ginger used
      had significant effects on the content of gingerols, but its overall influence
      depended on the solvent used. In order to maximize the extraction efficiency of
      gingerols, a combination of dry ginger, 95% ethanol, and the HP extraction method
      should be employed. The chromatographic fingerprints were obtained to
      differentiate the unknown components from all ginger extracts. The similarity of
      the chromatographic fingerprints was used to evaluate the differences among all
      extracts. It can be concluded that the chromatographic fingerprints are able to
      ensure the stability of each extract and have some correlation with the observed
      bioactivity.

PMID- 24672861
TI  - Use of statistical modeling to reassess the performance standard for the AOAC use
      dilution methods (955.15 and 964.02).
AB  - The AOAC Use-dilution methods (UDM) 955.15 (Staphylococcus aureus) and 964.02
      (Pseudomonas aeruginosa) are laboratory methods used to substantiate
      antimicrobial efficacy claims for liquid disinfectants on inanimate surfaces. The
      UDM is accepted by the U.S. Environmental Protection Agency for the purpose of
      product registration. To attain a hospital-level claim, testing against S. aureus
      and P. aeruginosa is required, and the product must pass against both microbes.
      Currently, the UDM's performance standard for a single 60-carrier test is the
      same for both microbes, and allows up to one positive carrier for the product to
      be considered as a pass. In this paper, the performance standards for these
      methods are reassessed using data from a 2009 five-laboratory collaborative study
      and a recently published statistical model. The reassessment focuses on the pass
      error rate for ineffective products and the fail-error rate for highly effective
      products. The calculations indicate that the pass-error rate is between 9 and 24%
      and the fail-error rate between 18 and 23% when the current performance standard
      is used for a single test. For product registration, a smaller pass-error rate
      (1%) historically has been maintained by requiring that a disinfectant pass three
      UDM tests for each of the two microbes; however, the calculations also indicate
      that the fail-error rate is between 42 and 45%. This large fail-error rate is a
      compelling reason to consider a new performance standard for the two UDM methods,
      955.15 (S. aureus) and 964.02 (P. aeruginosa). One alternative performance
      standard allows no more than six positive carriers out of 60 as a pass when using
      P. aeruginosa and no more than three positive carriers out of 60 when using S.
      aureus. In addition, the new performance standard requires that three UDM tests
      be performed with each of the two microbes, and the disinfectant must pass all
      six tests to be considered efficacious. The statistical calculations for this
      alternative performance standard indicate that the pass-error rate is no more
      than 3%, while the fail-error rate is as small as 5%. Based on these error rate
      calculations, proposed revisions to the performance standards for AOAC Methods
      955.15 and 964.02 are provided.

PMID- 24672862
TI  - Stability-indicating determination of rebamipide in the presence of its acid
      degradation products.
AB  - Four sensitive and precise stability-indicating methods for the determination of
      rebamipide (REB) in the presence of its acid-degradation products and in a
      pharmaceutical formulation were developed and validated. Method A used the first
      derivative of the ratio spectra (1DD) spectrophotometric method by measuring the
      peak amplitude at 249.4 nm (maximum) and at 259 nm (minimum), and at the total
      peak amplitude (from 249.4 to 259 nm, 1DD(249.4 + 259 nm)) in the range of 2-14
      microg/mL. This method yielded mean recoveries of 99.87 +/- 0.83, 100.04 +/-
      0.75, and 100.28 +/- 1.11%, respectively. Method B is a dual wavelength method,
      which allows the determination of REB in presence of its acid-degradation
      products by measuring the absorbance difference between 254 and 269 nm within a
      linearity range of 5-65 microg/mL; it showed a mean recovery of 99.84 +/- 1.06.
      Method C is a TLC-densitometric procedure in which REB was separated from its
      degradation products using a developing solution of methanol-chloroform-ammonia
      (8.5 + 1.5 + 0.5, v/v/v). The quantitative evaluation of REB at 329 nm was linear
      over the concentration range of 0.50-4.5 microg/band, with a mean recovery of
      99.49 +/- 0.99% even in the presence of up to 90% degradation products. Method D
      is an RP-HPLC procedure. It provided the complete separation of REB from its
      degradation products on an Xterra C18 column using phosphate buffer (pH 6, 0.01
      M)-methanol (1 + 1, v/v) as the mobile phase (UV detection at 254 nm). Recovery
      was 99.28 +/- 0.78% within the range of 10-190 microg/mL. The selectivity of the
      proposed methods was checked using laboratory-prepared mixtures. The proposed
      methods have been successfully applied to the analysis of REB in pharmaceutical
      dosage forms without interference from other dosage form excipients.

PMID- 24672863
TI  - Stability-indicating methods for the determination of erdosteine in the presence
      of its acid degradation products.
AB  - Four accurate, sensitive, and reproducible stability-indicating methods for the
      determination of erdosteine in the presence of its acid degradation products are
      presented. The first method involves processing the spectra by using a first
      derivative method at 229 nm in a concentration range of 10-70 microg/mL. The mean
      percentage recovery was 100.43 +/- 0.977. The second method is based on ratio
      spectra first derivative spectrophotometry at 227.4 and 255 nm over a
      concentration range of 10-70 microg/mL. The mean percentage recovery was 99.65 +/
      1.122% and 100.02 +/- 1.306% at 227.4 and 255 nm, respectively. The third method
      utilizes quantitative densitometric evaluation of the TLC of erdosteine in the
      presence of its acid degradation products, and uses methanol-chloroform-ammonia
      (7 + 3 +/- 0.01, v/v/v) as the mobile phase. TLC chromatograms were scanned at
      235 nm. This method analyzes erdosteine in a concentration range of 2.4-5.6
      microg/spot, with a mean percentage recovery of 100.03 +/- 1.015%. The fourth
      method is HPLC for the simultaneous determination of erdosteine in the presence
      of its acid degradation products. The mobile phase consists of water-methanol (65
      + 35, v/v). The standard curve of erdosteine showed good linearity over a
      concentration range of 10-80 microg/mL, with a mean percentage recovery of 99.90
      +/- 1.207%. These methods were successfully applied to the determination of
      erdosteine in bulk powder, laboratory-prepared mixtures containing different
      percentages of the degradation products, and pharmaceutical dosage forms. The
      validity of results was assessed by applying the standard addition technique. The
      results obtained agreed statistically with those obtained by a reported method,
      showing no significant differences with respect to accuracy and precision.

PMID- 24672864
TI  - Highly selective colorimetric method to determine gemifloxacin mesylate in the
      presence of a synthetic impurity.
AB  - A simple visible spectrophotometric method was developed for the determination of
      gemifloxacin mesylate (GFM) in tablets. The method was based on the formation of
      a yellow ion-pair complex between the basic nitrogen of the drug and the
      sulfonphthalein acid dye in phthalate buffer. The method was validated by the
      study of its specificity, linearity, precision, accuracy, and robustness. The
      assay was compared with an LC and a microbiological method, and the analysis of
      variance showed no significant difference between the methods (P>0.05). The
      results demonstrated that the visible spectrophotometric method is suitable for
      determination of GFM in tablets, even in the presence of a synthetic impurity.

PMID- 24672865
TI  - Method development and validation of LC and densitometric-TLC for simultaneous
      determination of pitavastatin calcium and ezetimibe in a binary mixture.
AB  - Two simple and accurate methods to determine pitavastatin calcium (PIT) and
      ezetimibe (EZE), in a binary mixture, were developed and validated using LC and
      densitometric-TLC. The LC separation was achieved on a Phenomenex Luna C18 column
      (250 x 4.6 mm id, 5 microm), in the isocratic mode using 0.1% orthophosphoric
      acid-acetonitriletriethylamine (19.8 + 80 + 0.2, v/v/v), pH 3.00 +/- 0.05, at a
      flow rate of 1.4 mL/min. The retention times were about 6.98 and 2.36 min for PIT
      and EZE, respectively. Quantification was achieved with a photodiode array
      detector at 235 nm over the concentration range of 0.5-5 microg/mL for each drug,
      with mean recoveries of 99.35 +/- 0.19% and 99.51 +/- 0.23% for PIT and EZE,
      respectively. The TLC separation was achieved on silica gel 60 F254 HPTLC plates
      using toluene-ethyl acetate-glacial acetic acid (59.8 + 40.0 + 0.2, v/v/v), as
      the mobile phase. The R(f) values were about 0.38 and 0.58 for PIT and EZE,
      respectively. Quantification was achieved with UV detection at 235 nm over the
      concentration range of 50-600 ng/spot for each drug, with mean recoveries of
      99.49 +/- 0.15% and 99.58 +/- 0.10% for PIT and EZE, respectively. Both methods
      were validated, and based on statistical results were found to be specific,
      accurate, precise, and robust. The methods were successfully applied for the
      determination of PIT and EZE in a binary mixture without any interferences from
      common excipients.

PMID- 24672866
TI  - Different techniques for the determination of tofisopam.
AB  - Five simple and sensitive methods were developed for the determination of
      tofisopam (TF). The first four are stability-indicating depending on the
      determination of TF in the presence of its degradation product, while the fifth
      depended on the determination of TF via its degradation product. Method A was
      based on first and second derivative spectrophotometry, D and 2D, measuring the
      amplitude at 298 and 332 nm in the case of 1D and at 312 and 344 nm in the case
      of 2D. Method B depended on measuring the peak amplitude of the first derivative
      of the ratio spectra 1DD at 336 nm. Method C was based on difference
      spectrophotometry by measuring deltaA at 366 nm. Method D was a TLC method using
      silica gel 60 F254 plates, the optimized mobile phase ethyl acetate-methanol
      ammonium hydroxide 10% (8.5 + 1.0 + 0.5, v/v/v), and quantification by
      densitometric scanning at 315 nm. In method E, spectrofluorometry was applied for
      the determination of TF via its degradation product; maximum emission was 383 nm
      when excitation was 295 nm. Linearities were obtained in the concentration range
      2-20 microg/mL for methods A, B, and C and 2-20 microg/band and 0.2-1.6 microg/mL
      for D and E, respectively. In method A, the mean recoveries were 99.45 +/- 0.287
      and 100.28 +/- 0.277% at 298 and 332 nm, respectively, in the case of 1D and
      99.40 +/- 0.245% and 99.50 +/- 0.292% at 312 and 344 nm, respectively in the case
      of 2D. The mean recovery was 100.03 +/- 0.523% at 366 nm in method B. Method C
      showed mean recovery of 100.20 +/- 0.642%. Recoveries for methods D and E were
      98.98 +/- 0.721 and 100.25 +/- 0.282%, respectively. The degradation product was
      obtained in acidic stress condition, separated, and identified by IR and mass
      spectral analysis, from which the degradation product was confirmed and the
      degradation pathway was suggested. The first four methods were specific for TF in
      the presence of different concentrations of its degradation product. The five
      proposed methods were successfully applied for the determination of TF in
      Nodeprine tablets. Statistical comparison among the results obtained by these
      methods and that obtained by the official method for the determination of the
      drug was made, and no significant differences were found.

PMID- 24672867
TI  - Stability-indicating micellar electrokinetic chromatography technique for
      simultaneous measurement of delapril and manidipine from a combination drug
      formulation.
AB  - A stability-indicating micellar electrokinetic chromatography (MEKC) method was
      developed and validated for simultaneous analysis of delapril (DEL) and
      manidipine (MAN) using salicylic acid as an internal standard. The MEKC method
      was performed using a fused-silica capillary (effective length of 72 cm) with 50
      mM of borate buffer and 5 mM of anionic surfactant sodium dodecylsulfate at pH
      9.0 as the background electrolyte. The separation was achieved at 25 kV applied
      voltage and 35 degrees C. The injection was performed at 50 mbar for 5 s, with
      detection at 208 nm. The method was linear in the range of 15-150 microg/mL (r2 =
      0.9966) for DEL and 5-50 microg/mL (r2 = 0.9985) for MAN with adequate results
      for the precision (< or = 1.87%) and accuracy (98.94% for DEL and 100.65% for
      MAN). The specificity of the method and its stability-indicating capability was
      demonstrated through forced degradation studies, which showed that there was no
      interference from the excipients. The Plackett-Burman experimental design was
      used for robustness evaluation, giving results within the acceptable range. The
      method was successfully applied for analysis of the drugs, and the results were
      compared to an LC method, resulting in nonsignificant differences (P = 0.78 and
      0.84 for DEL and MAN, respectively).

PMID- 24672868
TI  - Chiral separation of racemic naproxen by high-performance liquid chromatography
      with beta-CD/SiO2 as the chiral stationary phase.
AB  - A novel derivative beta-cyclodextrin (beta-CD) bonded silica gel (beta-CD/SiO2)
      was prepared via carbodiimide activation and used as a chiral stationary phase
      (CSP). The beta-CD/SiO2 CSP was characterized by X-ray photoelectron spectroscopy
      and FTIR spectroscopy to prove the successful immobilization of beta-CD onto the
      surface of the silica gel. The thermal behavior of the CSP was studied by
      differential scanning calorimetry and then used for the chiral separation of
      racemic naproxen using HPLC. Several factors affecting the separation efficiency
      of naproxen enantiomers were investigated systematically. The following
      parameters were selected: methanol-0.01 M phosphate buffer solution (85 + 15,
      v/v, pH 3.5) was the mobile phase, the flow rate was 1.0 mL/min, and the column
      temperature was 35 degrees C. Under optimal conditions, the racemic naproxen was
      efficiently separated with a resolution factor (R(S)) of 1.70 and a separation
      factor (alpha) of 1.25. This method was successfully used for the enantiomeric
      separation and purity assessment of naproxen in commercial naproxen sustained
      release tablets.

PMID- 24672869
TI  - Development of a capillary zone electrophoresis method for determination of
      mebendazole and levamisole hydrochloride in a combined tablet and a comparison
      with a LC method.
AB  - The separation and determination of mebendazole (MEB) and levamisole
      hydrochloride (LH) from a combination tablet by capillary zone electrophoresis
      (CZE) was developed and validated. The separation was performed in a 60 cm (50.5
      cm to detection window) x 75 microm internal diameter fused silica capillary
      using a background electrolyte of NaH2PO4 (20 mM/L, pH 3.0 ) at 25 kV. Good
      separation was obtained in less than 8 min. The LOQ values for LH and MEB were
      1.43 and 2.50 microg/mL, respectively; calibration curves were linear from 10 to
      500 microg/mL with r2 > 0.999. Mean recoveries of the analytes were greater than
      96%. In addition, a comparison with the LC method described in the 2010 Chinese
      Pharmacopoeia demonstrated that the developed CZE method was equally comparable
      with regard to linearity, sensitivity, precision, and accuracy, but the analysis
      time and reagent consumption were decreased. The CZE method is an effective and
      lower-cost alternative to the LC method.

PMID- 24672870
TI  - Evaluation of the Thermo Scientific SureTect Listeria monocytogenes Assay.
AB  - The Thermo Scientific SureTect Listeria monocytogenes Assay is a new real-time
      PCR assay for the detection of Listeria monocytogenes in food and environmental
      samples. This assay was validated using the AOAC Research Institute (AOAC-RI)
      Performance Tested Methods program in comparison to the reference method detailed
      in International Organization for Standardization 11290-1:1996, including
      Amendment 1:2004 with the following foods and food contact surfaces: smoked
      salmon, processed cheese, fresh bagged spinach, fresh cantaloupe, cooked prawns
      (chilled product), cooked sliced turkey meat (chilled product), ice cream, pork
      frankfurters, salami, ground raw beef meat (12% fat), plastic, and stainless
      steel. All matrixes were tested by Thermo Fisher Scientific, Microbiology
      Division, Basingstoke, UK. In addition, three matrixes (pork frankfurters, bagged
      lettuce, and stainless steel) were analyzed independently as part of the AOAC-RI
      controlled laboratory study by the University of Guelph, Canada. Using
      probability of detection (POD) statistical analysis, a significant difference was
      demonstrated between the candidate and reference methods for salami, cooked
      sliced turkey and ice cream in favor of the SureTect assay. For all other
      matrixes, no significant difference by POD was seen between the two methods
      during the study. Inclusivity and exclusivity testing was also conducted with 53
      and 30 isolates, respectively, which demonstrated that the SureTect assay was
      able to detect all serotypes of L. monocytogenes. None of the exclusivity
      isolates analyzed were detected by the SureTect assay. Ruggedness testing was
      conducted to evaluate the performance of the assay with specific method
      deviations outside the recommended parameters open to variation, i.e., enrichment
      time and temperature and lysis temperature, which demonstrated that the assay
      gave reliable performance. Accelerated stability testing was also conducted,
      validating the assay shelf life.

PMID- 24672871
TI  - Semiquantitative determination of mesophilic, aerobic microorganisms in cocoa
      products using the Soleris NF-TVC method.
AB  - The Soleris Non-fermenting Total Viable Count method was previously validated for
      a wide variety of food products, including cocoa powder. A matrix extension study
      was conducted to validate the method for use with cocoa butter and cocoa liquor.
      Test samples included naturally contaminated cocoa liquor and cocoa butter
      inoculated with natural microbial flora derived from cocoa liquor. A probability
      of detection statistical model was used to compare Soleris results at multiple
      test thresholds (dilutions) with aerobic plate counts determined using the AOAC
      Official Method 966.23 dilution plating method. Results of the two methods were
      not statistically different at any dilution level in any of the three trials
      conducted. The Soleris method offers the advantage of results within 24 h,
      compared to the 48 h required by standard dilution plating methods.

PMID- 24672872
TI  - Detection and identification of transgenic elements by fluorescent-PCR-based
      capillary gel electrophoresis in genetically modified cotton and soybean.
AB  - A detection method for genetically modified foods is an essential regulatory
      requirement for many countries. The present study is aimed at developing a
      qualitative method for detection of genetically modified organisms by combining
      PCR methodology with capillary gel electrophoresis (PCR-CGE) in a sequencing
      platform to detect Bacillus thuringiensis (Bt)-cotton (MON 531) and Roundup Ready
      (RR) soybean (GTS 40-3-2). A sensitive duplex PCR-CGE method was developed in
      which target DNA sequences (35S and Nos) were separated both by size and color to
      detect 0.01% Cry1Ac DNA (w/w) in Bt-cotton. A multiplex PCR-CGE method was
      developed to simultaneously detect four targets such as Sad1, Cry1Ac, 35S, and
      Nos in Bt-cotton. Four novel PCR primers were designed to customize amplicon size
      for multiplexing for better visualization of multiple peaks. The LOD for CrylAc
      DNA specific PCR was 0.01% for Bt-cotton. The LOD for multiplex PCR assay was
      0.05% for Bt-cotton. A singleplex PCR-CGE method was developed to detect Lec, 35S
      and Nos in a trace sample of RR soybean grain powder (0.1%, w/w). This study
      demonstrates a PCR-CGE-based method for the qualitative detection of 35S, Nos and
      Cry1Ac targets associated with genetically modified products.

PMID- 24672873
TI  - Analysis of cocoa flavanols and procyanidins (DP 1-10) in cocoa-containing
      ingredients and products by rapid resolution liquid chromatography: single
      laboratory validation.
AB  - Recently, a multilaboratory validation (MLV) of AOAC Official Method 2012.24 for
      the determination of cocoa flavanols and procyanidins (CF-CP) in cocoa-based
      ingredients and products determined that the method was robust, reliable, and
      transferrable. Due to the complexity of the CF-CP molecules, this method required
      a run time exceeding 1 h to achieve acceptable separations. To address this
      issue, a rapid resolution normal phase LC method was developed, and a single
      laboratory validation (SLV) study conducted. Flavanols and procyanidins with a
      degree of polymerization (DP) up to 10 were eluted in 15 min using a binary
      gradient applied to a diol stationary phase, detected using fluorescence
      detection, and reported as a total sum of DP 1-10. Quantification was achieved
      using (-)-epicatechin-based relative response factors for DP 2-10. Spike recovery
      samples and seven different types of cocoa-based samples were analyzed to
      evaluate the accuracy, precision, LOD, LOQ, and linearity of the method. The
      within-day precision of the reported content for the samples was 1.15-5.08%, and
      overall precision was 3.97-13.61%. Spike-recovery experiments demonstrated
      recoveries of over 98%. The results of this SLV were compared to those previously
      obtained in the MLV and found to be consistent. The translation to rapid
      resolution LC allowed for an 80% reduction in analysis time and solvent usage,
      while retaining the accuracy and reliability of the original method. The savings
      in both cost and time of this rapid method make it well-suited for routine
      laboratory use.

PMID- 24672874
TI  - Novel Cd(II) ion imprinted polymer coated on multiwall carbon nanotubes as a
      highly selective sorbent for cadmium determination in food samples.
AB  - The application of a novel Cd(II) ion imprinted polymer coated on multiwall
      carbon nanotubes was investigated for preconcentration and determination of low
      levels of Cd ions. This novel sorbent was characterized by scanning electron
      microscopy, thermal gravimetric/differential thermal analysis, elemental
      analysis, and FTIR spectrometry. Effects of various factors, such as pH of the
      sample solution, eluent (type, concentration, and volume), and flow rates of the
      sample and eluent, were evaluated in this study. To investigate the selectivity
      of the sorbent toward Cd(II) ions, the effects of a variety of ions on
      preconcentration and recovery of Cd(II) ions were investigated. The LOD was 1.3
      ng/mL; the recovery and RSD of the method were 96.4% and below 3.1%,
      respectively. Validation of the method was performed by analyzing some standard
      reference materials with certified Cd(II) concentrations. Finally, the sorbent
      was applied for separation and determination of Cd(II) ions in food samples.

PMID- 24672875
TI  - Stability of chlorophenols and their acetylated derivatives in water: sample
      storage procedures.
AB  - The determination of chlorophenols (CPs) in water samples is a subject of
      increasing interest. Reduction of sample storage space and the stability of CPs
      when present at very low levels are still problems that deserve research. The
      stability of CPs at ng/L levels at different temperatures and in the presence or
      absence of sodium carbonate and acetic anhydride was studied for up to 39 days.
      Stable and reproducible CP concentrations for about a month of storage in both
      river and wastewater were achieved in two storage conditions as follows: at -18
      degrees C with addition of 10% sodium chloride; and at 4 degrees C with addition
      of both 10% sodium chloride and 10 mglmL sodium carbonate. These sample
      treatments are good alternatives to the immobilization of CPs on SPE cartridges
      in terms of both analyte stability and saving of storage space.

PMID- 24672876
TI  - Determination of fungicides in fruit juice by ultrasound-assisted dispersive
      liquid-liquid microextraction based on solidification of floating organic solvent
      droplets followed by high performance liquid chromatography.
AB  - Ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) based on
      solidification of the floating organic solvent droplets (SFO) combined with HPLC
      was used for determination of five fungicides in fruit juice samples. 1
      Dodecanol, which has a low density and low toxicity, was used as the extraction
      solvent in UA-DLLME. The solidification of floating organic droplets facilitates
      the transfer of analytes from the aqueous phase to the organic phase. This method
      was easy, quick, inexpensive, precise, and linear over a wide range. Under the
      optimized conditions, the enrichment factors for a 5 mL fruit juice sample were
      25 to 56, and the LODs for the five fungicides ranged from 5 to 50 microg/L. The
      average recoveries ranged from 71.8 to 118.2% with RSDs of 0.9 to 13.9%.
      Application of the DLLME-SFO technique allows successful separation and
      preconcentration of the fungicides at a low concentration level in fruit juice
      samples.

PMID- 24672877
TI  - New HPLC and fluorometric methods for the determination of pyriproxyfen and
      pyridalyl insecticide residues in tomatoes.
AB  - Two sensitive, selective, and precise methods for the determination of
      pyriproxyfen and pyridalyl insecticide residues in tomatoes have been developed.
      The first method is HPLC with UV detection in which pyriproxyfen and pyridalyl
      were extracted with ethyl acetate and acetone, respectively, followed by cleanup
      using column chromatography. The recoveries ranged from 86.03 to 94.55 for
      pyriproxyfen and 95.08 to 99.38% for pyridalyl in tomato samples. The LOD of the
      method was 0.217 ppm for pyriproxyfen and 0.1866 ppm for pyridalyl. The second
      method depends on direct fluorometric determination of pyriproxyfen and pyridalyl
      in acetic and sulfuric acid at excitation and emission wavelengths of 320 and 646
      nm, respectively. The recoveries of pyriproxyfen and pyridalyl in tomato samples
      ranged from 88 to 98% and 86 to 93%, respectively. The LOD of the method was
      0.146 ppm for pyriproxyfen and 0.078 ppm for pyridalyl. Both methods were applied
      successfully to determine residues and rate of disappearance of pyriproxyfen and
      pyridalyl from tomatoes.

PMID- 24672878
TI  - Development and application of a microwave-assisted extraction and LC/MS/MS
      methodology to the determination of antifouling booster biocides in sea mullets
      (Mugil cephalus) organisms.
AB  - A method is presented for the extraction, preconcentration, and determination of
      two commonly used booster biocides, Irgarol 1051 and diuron, in samples of muscle
      and liver tissues from Mugil cephalus by microwave-assisted extraction (MAE)
      followed by SPE for the preconcentration and cleanup step, coupled with LC/MS/MS.
      The optimum conditions for MAE were established as power 200 W and irradiation
      time 4 min. Using these conditions, the LOD was 0.13 ng/g for diuron and 0.10
      ng/g for Irgarol 1051. The recoveries calculated at three concentration levels
      (0.5, 5, and 50 ng/g) were greater than 74%. Repeatability was less than 7.5% and
      reproducibility less than 12.7%. The optimized method was used to monitor these
      compounds in M. cephalus from different harbors of Gran Canaria Island. The
      samples were collected bimonthly and processed following the optimized method.
      High levels of Irgarol 1051 (6.9 +/- 1.03 ng/g) were found in the liver, while
      diuron was undetected. However, diuron was found in the muscle (1.41 +/- 0.45
      ng/g). The proposed sentinel organism could be used in tropical and subtropical
      regions to continuously biomonitor for booster biocides over long periods of
      time. This technique could be a useful tool for improving the management of ocean
      and coastal waters.

PMID- 24672880
TI  - C18 bonded silica membrane disk modified with Cyanex 302 for Cr(III) and Cr(VI)
      speciation and flame atomic absorption spectrometric determination.
AB  - A new SPE method for speciation of Cr(III) and Cr(VI) has been developed using a
      Cyanex 302-impregnated C18 bonded silica membrane disk followed by flame atomic
      absorption spectrometric determination. The influence of various parameters, such
      as pH, flow rate, volume of sample solution, amount of Cyanex 302, and eluent
      type, concentration, and flow rate, on Cr(III) retention, were systematically
      studied. Cr(III) was quantitatively recovered from the modified sorbent at pH
      4.5, while the recovery of Cr(VI) was negligible (0.5 +/- 0.5 microg) throughout
      the pH range studied for its sorption, thus facilitating their separation and
      speciation. Most of the elements associated with Cr(III) did not show strong
      interference during its sorption. The sorption capacity of modified disk for
      Cr(III) was 117.6 +/- 0.8 microg, and its enrichment factor for Cr(III) was 37.
      The LOD and LOQ of the method for Cr(III) were 0.88 and 2.93 microg/L,
      respectively. The efficiency of the disk for Cr(III) recovery remained unchanged
      up to 24 cycles. A certified reference material (BCR-701) was analyzed to
      validate the accuracy of method developed for Cr(III). The method was applied to
      the determination of Cr(III) and Cr(VI) species in tap water and an industrial
      effluent sample, with RSD < or = 1.0%.

PMID- 24672879
TI  - Enrichment of copper as 1-(2-pyridylazo)-2-naphthol complex by the combination of
      dispersive liquid-liquid microextraction/flame atomic absorption spectrometry.
AB  - A rapid, simple, selective, economical, and sensitive dispersive liquid-liquid
      microextraction methodology has been established for the preconcentration of
      copper (Cu) at trace levels. The Cu(II) was complexed with 1-(2-pyridylazo)-2
      naphthol; ethanol and carbon tetrachloride were used as disperser and extraction
      solvents, respectively. To obtain quantitative recovery of Cu(II), the effects of
      parameters influencing its extraction efficiency and subsequent determinations,
      i.e., pH, amount of complexing reagent, extraction time, and type and volume of
      disperser and extraction solvents, were examined. LOD and LOQ were 0.06 and 0.20
      microg/L, respectively. The enrichment factor of the proposed method was 60, and
      the RSD <5%. TMDA 51.3 and TMDA 70 fortified water certified reference materials
      were analyzed for validation of the procedure. The developed microextraction
      procedure has been used for the preconcentration of Cu(II) in water samples with
      acceptable results.

PMID- 24672881
TI  - Simultaneous determination of matrine and berberine in fruits, vegetables, and
      soil using ultra-performance liquid chromatography/tandem mass spectrometry.
AB  - An ultra-performance LC/tandem MS (UPLC/MS/MS) method for the simultaneous
      quantification and identification of matrine and berberine, alkaloids widely used
      in plant fungicides, has been developed and validated. Methanol or 1% ammonia
      acetonitrile were selected as extraction solvents, and primary secondary amine
      sorbent was chosen for cleanup to achieve satisfactory recoveries in accordance
      with European Union guidelines. The chromatographic separation was carried out on
      a hydrophilic interaction LC column with a UPLC/MS/MS-based method to improve the
      retentions and shapes of the peaks. Method validation was performed for
      linearity, repeatability, interday precision, and sensitivity. Recoveries and
      RSDs were acceptable (73.1-109.3% recovery, RSD < or = 15.8%). The LODs varied
      from 0.34 to 1.07 microg/kg for matrine and 0.09 to 0.18 microg/kg for berberine,
      while the LOQs ranged from 1.12 to 3.58 microg/kg for matrine and 0.31 to 0.60
      microg/kg for berberine. This method was successfully and efficiently applied for
      the analysis of matrine and berberine in real samples.

PMID- 24672882
TI  - Determination of nickel in water, food, and biological samples by electrothermal
      atomic absorption spectrometry after preconcentration on modified carbon
      nanotubes.
AB  - A new and sensitive SPE method using modified carbon nanotubes for extraction and
      preconcentration, and electrothermal atomic absorption spectrometric
      determination of nickel (Ni) in real samples at ng/L levels was investigated.
      First, multiwalled carbon nanotubes were oxidized with concentrated HNO3, then
      modified with 2-(5-bormo-2-pyridylazo)-5-diethylaminophenol reagent. The
      adsorption was achieved quantitatively on a modified carbon nanotubes column in a
      pH range of 6.5 to 8.5; the adsorbed Ni(II) ions were then desorbed by passing
      5.0 mL of 1 M HNO3. The effects of analytical parameters, including pH of the
      solution, eluent type and volume, sample volume, flow rate of the eluent, and
      matrix ions, were investigated for optimization of the presented procedure. The
      enrichment factor was 180, and the LOD for Ni was 4.9 ng/L. The method was
      applied to the determination of Ni in water, food, and biological samples, and
      reproducible results were obtained.

PMID- 24672883
TI  - Determination of trace amounts of ethylene glycol and its analogs in water
      matrixes by liquid chromatography/tandem mass spectrometry.
AB  - Contamination of drinking water by ethylene glycol (EG) is a public health
      concern. EG causes adverse health effects in humans and animals, including
      cardiopulmonary and acute renal failure. EG and other glycols, such as propylene
      glycol (PG) are major components in antifreeze liquids, which may be the main
      source of contamination of ground water. A sensitive LC/electrospray ionization
      (ESI)-MS/MS method was developed to measure trace amounts of EG, diethylene
      glycol, and 1,2- and 1,3-PG in several water sources, including municipal tap,
      lake, river, and salinated water. In this method, glycols in water samples were
      derivatized with benzoyl chloride by the Schotten-Baumann reaction, followed by
      liquid-liquid extraction using pentane as the organic solvent prior to the LC/ESI
      MS/MS determination. QC included analysis of a method blank and samples fortified
      at low and high levels. Analytical data showed excellent linear calibration for
      all observed glycols, with good precision and accuracy. The method detection
      limits for the studied glycols ranged from 1.9 to 6.1 ng/mL across the water
      matrixes tested. This method is suitable to help assess water quality in areas
      that may be prone to glycol contamination.

PMID- 24672884
TI  - Determination of trace inorganic mercury species in water samples by cloud point
      extraction and UV-vis spectrophotometry.
AB  - A new micelle-mediated extraction method was developed for preconcentration of
      ultratrace Hg(II) ions prior to spectrophotometric determination. 2-(2'
      Thiazolylazo)-p-cresol (TAC) and Ponpe 7.5 were used as the chelating agent and
      nonionic surfactant, respectively. Hg(II) ions form a hydrophobic complex with
      TAC in a micelle medium. The main factors affecting cloud point extraction
      efficiency, such as pH of the medium, concentrations of TAC and Ponpe 7.5, and
      equilibration temperature and time, were investigated in detail. An overall
      preconcentration factor of 33.3 was obtained upon preconcentration of a 50 mL
      sample. The LOD obtained under the optimal conditions was 0.86 microg/L, and the
      RSD for five replicate measurements of 100 microg/L Hg(II) was 3.12%. The method
      was successfully applied to the determination of Hg in environmental water
      samples.

PMID- 24672885
TI  - Development and validation of an alternative to conventional pretreatment methods
      for residue analysis of butachlor in water, soil, and rice.
AB  - A rapid and effective alternative analytical method for residues of butachlor in
      water, soil, and rice was established. The operating variables affecting
      performance of this method, including different extraction conditions and cleanup
      adsorbents, were evaluated. The determination of butachlor residues in soil,
      straw, rice hull, and husked rice was performed using GC/MS after extraction with
      n-hexane and cleanup with graphite carbon black. The average recoveries ranged
      from 81.5 to 102.7%, with RSDs of 0.6-7.7% for all of the matrixes investigated.
      The limits of quantitation were 0.05 mg/kg in water and rice plant, and 0.01
      mg/kg in soil, straw, rice hull, and husked rice. A comparison among this
      proposed method, the conventional liquid-liquid extraction, the Quick, Easy,
      Cheap, Effective, Rugged, and Safe method, and Soxhlet extraction indicated that
      this method was more suitable for analyzing butachlor in rice samples. The
      further validation of the proposed method was carried out by Soxhlet extraction
      for the determination of butachlor residues in the husked rice samples, and the
      residue results showed there was no obvious difference obtained from these two
      methods. Samples from a rice field were found to contain butachlor residues below
      the maximum residue limits set by China (0.5 mg/kg) and Japan (0.1 mg/kg). The
      proposed method has a strong potential for application in routine screening and
      processing of large numbers of samples. This study developed a more effective
      alternative to the conventional analytical methods for analyzing butachlor
      residues in various matrixes.

PMID- 24672886
TI  - Generalized net analyte signal standard addition as a novel method for
      simultaneous determination: application in spectrophotometric determination of
      some pesticides.
AB  - Simultaneous spectrophotometric determination of three neonicotinoid insecticides
      (acetamiprid, imidacloprid, and thiamethoxam) by a novel method named generalized
      net analyte signal standard addition method (GNASSAM) in some binary and ternary
      synthetic mixtures was investigated. For this purpose, standard addition was
      performed using a single standard solution consisting of a mixture of standards
      of all analytes. Savings in time and amount of used materials are some of the
      advantages of this method. All determinations showed appropriate applicability of
      this method with less than 5% error. This method may be applied for linearly
      dependent data in the presence of known interferents. The GNASSAM combines the
      advantages of both the generalized standard addition method and net analyte
      signal; therefore, it may be a proper alternative for some other multivariate
      methods.

PMID- 24672887
TI  - Determination of ammonia by designing an optode based on immobilization of a
      Co(III)-Schiff base complex on a triacetylcelluose membrane.
AB  - A novel ammonia optode was designed using [4-methyl-N,N'-bis(salicylidene)-1,2
      phenylenediamine] tributylphosphincobalt(III) perchlorate monohydrate [Co(4
      MeSaloph)(PBu)3]+ complex coated on a triacetylcellulose membrane. The sensor
      could be used at a wavelength of 378 nm to detect ammonia in the range of 8.3 x
      10(-4) and -1.25 x 10(-2) M in borate buffer (pH 10). The LOD was found to be 9.5
      x 10(-5) M. The response time of the optode was 2-3 min and depended on the
      concentration of ammonia. This optode was successfully applied for the
      determination of ammonia in drinking water.

PMID- 24672888
TI  - Determination of corticosteroids, anabolic steroids, and basic nonsteroidal anti
      inflammatory drugs in milk and animal tissues.
AB  - A quantitative LC/MS/MS method was developed for the determination of 14
      steroidal compounds and three basic nonsteroidal anti-inflammatory drugs
      (detected as metabolites) in bovine milk and animal muscle tissue. The proposed
      method is sufficiently sensitive and highly selective for residue applications.
      The described approach offers the possibility to detect, quantify, and confirm
      anti-inflammatory drugs belonging to two widely diverging chemical categories.
      The employed single-stage SPE step (mixed mode cation exchange) retains both
      steroids and basic metabolites of nonsteroidal anti-inflammatory drugs. The
      method is capable of handling widely diverging relevant concentration ranges (0.1
      microg/kg for dexamethasone and 100 microg/kg for metamizol metabolites) for the
      individual compounds with a single extraction, cleanup, and LC/MS/MS procedure.
      It provides good analyte precision and accuracy data.

PMID- 24672889
TI  - Development and method validation for the determination of nitroimidazole
      residues in salmon, tilapia and shrimp muscle.
AB  - The use of nitroimidazoles in aquacultured fish has been banned in many countries
      due to the suspected mutagenic and carcinogenic effects of these compounds. In
      response to the need to conduct residue testing of these compounds in fish, a
      simple, rapid, and sensitive method was developed and validated that is suitable
      for regulatory monitoring of nitroimidazole residues and their hydroxy
      metabolites in fish muscle tissue. Following solvent extraction of homogenized
      tissue and clean-up using a C18 SPE cartridge, analyses were conducted by ultra
      performance UPLC-MS/MS. A precursor ion and two product ions were monitored for
      each of the parent compounds and metabolites included in the method. The
      validated method has an analytical range from 1 to 50 ng/g in the representative
      species (tilapia, salmon, and shrimp), with an LOD and LOQ ranging from 0.07 to
      1.0 nglg and 0.21 to 3.0 nglg, respectively, depending on the analyte. Recoveries
      ranged from 81 to 124% and repeatability was between 4 and 17%. HorRat values
      were within typical limits of acceptability for a single laboratory. Working
      standards were stable for 12 months, extracts were stable for 5 days, and tissues
      for 2 months under appropriate storage conditions. This method was determined to
      be suitable for routine use for screening, quantification, and confirmation of
      nitroimidazole residues in a residue monitoring program for fish with regulatory
      oversight.

PMID- 24672890
TI  - Use of second generation H1 antihistamines in special situations.
AB  - Antihistamine drugs are one of the therapeutic classes most used at world level,
      at all ages and in multiple situations. Although in general they have a good
      safety profile, only the more recent drugs (second generation antihistamines)
      have been studied specifically with regard to the more important safety aspects.
      Given the variety of antihistamine drugs, they cannot all be considered
      equivalent in application to various special clinical situations, so that the
      documented clinical experience must be assessed in each case or, in the absence
      of such, the particular pharmacological characteristics of each molecule for the
      purpose of recommendation in these special situations. In general, there are few
      clinical studies published for groups of patients with kidney or liver failure,
      with concomitant multiple pathologies (such as cardiac pathology), in extremes of
      age (paediatrics or geriatrics) and in natural stages such as pregnancy or
      lactation, but these are normal situations and it is more and more frequent
      (among the elderly) for antihistamine drugs to be recommended. This review sets
      out the more relevant details compiled on the use of antihistamines in these
      special situations.

PMID- 24672891
TI  - H1 antihistamines and benzodiazepines. Pharmacological interactions and their
      impact on cerebral function.
AB  - Antihistamines (AH) have been classified into first and second generation
      according to their pharmacokinetic properties, structural characteristics and
      adverse effects. The effects on the central nervous system (CNS) are determined
      basically by their capacity to cross the hematoencephalic barrier and attach to
      central H1 receptors. Benzodiazepines (BZD) are drugs with effects on the CNS
      following their union to the specific location of GABA receptors type A. At low
      doses, the BZD have sedative and anticonvulsive effects, and as the dose
      increases it leads to sedation, amnesia and finally unconsciousness. Various
      studies have been made on the possible interaction between the BZD and the AH H1
      with special attention to their effect on the CNS. In some cases these were
      studies to assess the safety of this association and in others, the aim was
      different: to see if their joint administration gives a better therapeutic result
      in pathology related with anxiety syndrome or insomnia. In general it can be said
      that first generation AH interact with the BZD increasing the sedative effects of
      the latter. However, second generation AH do not increase these sedative effects,
      which makes them the chosen drugs to treat allergic rhinitis/rhino-conjunctivitis
      and urticaria in patients also receiving BZD.

PMID- 24672892
TI  - Antihistamines in drivers, aircrew and occupations of risk.
AB  - The most commonly occurring allergic diseases can involve a daytime drowsiness
      associated with the condition itself. The antihistamines used in their treatment
      can also have central effects and affect certain occupations concerned with risk,
      road safety and maritime and air navigation. Cognitive tests, experimental
      studies and epidemiological data recommend avoiding 1st generation antihistamines
      for people who must drive regularly and/or professions concerned with safety.
      Although there are no comparative studies on real driving between 1st and 2nd
      generation antihistamines, in this type of patients there should be a preference
      for prescribing those with least possible central effect, especially those which
      are a good substrate for transmembrane transporter pumps such as P-glycoprotein
      and therefore have a low capacity for crossing the hematoencephalic barrier, thus
      allowing a broader window for therapy. In this sense, bilastine is a good P
      glycoprotein substrate and shows good tolerance at CNS level, in both
      psychometric trials and real driving test protocols, even at double the dose
      recommended in the technical file.

PMID- 24672893
TI  - Post-mortem computed tomography (PMCT) and PMCT-angiography after cardiac
      surgery. Possibilities and limits.
AB  - BACKGROUND: PMCT is a well-known tool of the forensic pathologist. It is employed
      worldwide. PMCT-angiography offers additional insights. This paper intends to
      demonstrate possibilities of both methods after cardiac surgery. MATERIAL AND
      METHODS: Exemplary cases with typical findings were selected from our own
      collection. PMCT was performed as whole body CT (1mm slice, pitch 1.5, 130kV, 180
      130mAs, 16 slice MDCT). In PMCT-angiography, contrast material (1.2 litres) is
      injected into the arteries (arterial phase, also documented with a whole body
      CT). Thereafter, contrast material is injected into the veins (venous phase, also
      documented with a whole body CT). The final CT is obtained after circulation has
      been provoked with a special pump (circulatory phase). RESULTS: PMCT visualised
      pseudoarthrosis and fractures of the sternum, implanted valves (TAVI) encroaching
      the ostia of the coronary arteries, bleeding and pericardial tamponade. PMCT
      angiography showed the sources of the bleeding, vascular stenosis and obstruction
      and modified vascular supply. With respect to the postoperative care, malposition
      of tubes, drainages and complication of punctures could be seen. CONCLUSION: PMCT
      and PMCT-angiography can visualise complications and the cause of death. Such
      knowledge may allow for prevention of suffering and death. It may also aid in
      improving valve design and implantation procedures.

PMID- 24672894
TI  - Verification of whiplash-associated disorders in forensic medical practice. Part
      II--Objectivization of injuries.
AB  - In clinical practice, cervical spine distortion or whiplash-associated disorders
      (WADs) are diagnosed exclusively on the basis of subjective complaints presented
      by the patients and by information that they were involved in traffic collisions.
      Therefore, from the forensic point of view, it is essential to verify all
      diagnosed WADs in the context of an extremely important and already proven mental
      component of the reported complaints and lack of objective changes in imaging
      examinations. The study presents suggestions regarding objectivization of acute
      episodes of cervical spine distortion in traffic accident victims based on
      medical criteria and accident circumstances. The knowledge of technical aspects
      of the circumstances of WADs facilitates medical evaluation of their
      consequences; moreover, the use of combined criteria allows for the assessment of
      probability of WADs in a particular traffic accident victim.

PMID- 24672895
TI  - Employment of auditory brainstem responses in verification and objectification of
      impairment of hearing in criminal legal proceedings
AB  - There are numerous subjective and objective diagnostic methods which allow for
      assessing the degree of the hearing loss and its anatomical location. Despite
      widespread availability of those methods, especially the subjective ones, such as
      pure tone audiometry or speech audiometry, diagnostic errors still frequently
      occur. They may lead to drawing false conclusions and issuing a fallacious
      medicolegal expert opinion, which obviously aggravates the situation of the
      defendant. Medicolegal experience has shown that these errors may result from
      employment of classic, subjective only methods of hearing examination and failure
      to perform objective tests, in particular auditory brainstem responses (ABR),
      autoacustic emissions (OAEs) and audiometry impendance (AI).

PMID- 24672896
TI  - Polish population data for 17 Y-STRs and 8 Y-SNPs markers
AB  - The aim of our study was to establish the genetic differentiation of the
      population of the province of Wielkopolska (Greater Poland) for 17 Y-STRs and 8 Y
      SNPs and comparison of the Polish population with other selected populations. The
      investigations included 201 unrelated male inhabitants of the Greater Poland
      region We found 184 unique haplotypes for 17 Y-STR. The haplotype discrimination
      capacity was 0.96. The most frequent haplotype Ht-50 was found in 3 samples and 7
      haplotypes observed twice. Further, the same samples were analyzed with Y-8 SNPs
      markers. We obtained 40 haplotypes. The haplotype discrimination capacity was
      0.20. The most frequent haplotype was presented in 38 samples. A total of 4
      different haplogroups were established. Haplogroup K= 19%, IJ = 7%, R1a1 = 59%
      and R1b = 15%. The HD value of Y-SNPs/Y-STRs was 0.9883.

PMID- 24672897
TI  - A unique case of malignant neoplasm--choriocarcinoma in a 24-year-old man-
      difficulties in differential diagnostics of intracranial injuries in the aspect
      of medicolegal opinion
AB  - Differential diagnostics of pathologic and traumatic lesions based on image
      techniques may in some cases cause serious difficulties or even be the cause of a
      medical error resulting in incorrect medicolegal opinion. The authors present a
      unique case of primary malignant neoplasm of the testicle (choriocarcinoma) in a
      24-year-old man. Several days after the event, he was admitted to Department of
      Neurology with CT-confirmed traumatic intracerebral hematoma communicating with
      the ventricular system. Discharged in a good general condition, the patient died
      several days later. A postmortem examination combined with histopathology
      demonstrated numerous metastases of the primary carcinoma, which also involved
      the brain, arousing suspicions of head injury in consequence of a crime.

PMID- 24672898
TI  - Causes of problems in multidisciplinary bitemark analysis
AB  - Since a successful bitemark analysis depends on many factors, it is important
      that the phases preceding the analysis be carried out as thoroughly as possible.
      Interpretive errors in the analysis arise primarily from the complex nature of
      bitemarks, but also as a result of faulty research methodology, false assumptions
      or technical errors made during the identification and documentation process. The
      key role is played by qualifications, knowledge and experience of experts
      involved in the investigations. In case bitemarks are detected, it is recommended
      to seek consultations by forensic odontologists or members of an
      interdisciplinary team experienced in bitemark analysis. The thus obtained
      information allows for gathering evidence guaranteeing a reliable expert opinion.

PMID- 24672899
TI  - On the history of opium
AB  - Most likely, opium was the first narcotic substance discovered at the dawn of
      humankind. The history of drug addiction is immensely rich and allows for tracing
      the long way humankind had to travel to reach the contemporary level of
      consciousness with respect to narcotic substances. A retrospective view of drug
      addiction that takes into consideration the historical context, while extending
      our knowledge, also allows for a better understanding of today's problems. The
      report presents elements of a retrospective view of problems associated with
      addiction to opium, morphine and heroin over the centuries, what is a subject of
      scientific interest in contemporary toxicology.

PMID- 24672900
TI  - Duties of the Psychiatric Committee for Preventive Measures. Present situation
      and proposed normative changes
AB  - The aim of this paper is to analyze the present legal model of the Psychiatric
      Committee for Preventive Measures and formulate proposed changes in regulations
      based on research findings. In 2003 the legislator delegated the qualifying
      procedures to the Committee, which resulted in lengthening the time until the
      moment of detaining the convict in a closed facility, which may cause harm to
      both the convict and the society. It is proposed that the classification be
      performed by experts, who must be heard by the court anyway before preventive
      measures are decreed, with the possibility of consulting the Committee in
      difficult or doubtful cases, if needed. Most tasks of the Committee, however,
      should be related to exercising control and to do this, it is necessary for the
      Committee to liaise with the court's penitentiary supervisors.

PMID- 24672901
TI  - A conceptual framework for associational effects: when do neighbors matter and
      how would we know?
AB  - Interactions between individual consumer and resource organisms can be modified
      by neighbors, e.g., when herbivory depends on the identity or diversity of
      neighboring plants. Effects of neighbors on consumer-resource interactions
      ("associational effects") occur in many systems, including plant-herbivore
      interactions, predator-prey interactions (mimicry), and plant-pollinator
      interactions. Unfortunately, we know little about how ecologically or
      evolutionarily important these effects are because we lack appropriate models and
      data to determine how neighbor effects on individuals contribute to net
      interactions at population and community levels. Here we supply a general
      definition of associational effects, review relevant theory, and suggest
      strategies for future theoretical and empirical work. We find that mathematical
      models from a variety of fields suggest that individual-level associational
      effects will influence population and community dynamics when associational
      effects create local frequency dependence. However, there is little data on how
      local frequency dependence in associational effects is generated, or on the form
      or spatial scale of that frequency dependence. Similarly, existing theory lacks
      consideration of nonlinear and spatially explicit frequency dependence. We
      outline an experimental approach for producing data that can be related to models
      to advance our understanding of how associational effects contribute to
      population and community processes.

PMID- 24672902
TI  - Darwin's diagram of divergence of taxa as a causal model for the origin of
      species.
AB  - On the basis that Darwin's theory of evolution encompasses two logically
      independent processes (common descent and natural selection), the only figure in
      On the Origin of Species (the Diagram of Divergence of Taxa) is often interpreted
      as illustrative of only one of these processes: the branching patterns
      representing common ancestry. Here, I argue that Darwin's Diagram of Divergence
      of Taxa represents a broad conceptual model of Darwin's theory, illustrating the
      causal efficacy of natural selection in producing well-defined varieties and
      ultimately species. The Tree Diagram encompasses the idea that natural selection
      explains common descent and the origin of organic diversity, thus representing a
      comprehensive model of Darwin's theory on the origin of species. I describe
      Darwin's Tree Diagram in relation to his argumentative strategy under the vera
      causa principle, and suggest that the testing of his theory based on the evidence
      from the geological record, the geographical distribution of organisms, and the
      mutual affinities of organic beings can be framed under the hypothetico-deductive
      method. Darwin's Diagram of Divergence of Taxa therefore represents a broad
      conceptual model that helps understanding the causal construction of Darwin's
      theory of evolution, the structure of his argumentative strategy, and the nature
      of his scientific methodology.

PMID- 24672903
TI  - "Workforce issues hinder next generation of nurses".

PMID- 24672904
TI  - Ward pressures hit placements.

PMID- 24672905
TI  - One in four trusts let HCAs start work on wards with no training.

PMID- 24672906
TI  - "Why do nurses feel unable to challenge doctors' decisions"?

PMID- 24672907
TI  - "Dementia care shop breaks down barriers and stigma".

PMID- 24672908
TI  - Hepatitis B: prevalence and pathophysiology.
AB  - Chronic hepatitis B is a growing worldwide public health issue. Its prevalence
      and the mode of transmission of the virus varies greatly between parts of the
      world. Prevalence is rising in the UK due to an increase in migration from areas
      with a high prevalence of chronic hepatitis B. This article, the first of a two
      part series, discusses the prevalence and pathophysiology of chronic hepatitis B,
      as well as recommendations for screening high-risk groups and immunisation
      against the disease. Part two discusses the management of the virus.

PMID- 24672909
TI  - A nurse-led community hepatitis B clinic.
AB  - Patients with chronic hepatitis B are usually managed by specialist teams in
      secondary care. This article explores some of the challenges of transferring
      aspects of these patients' care to a primary care setting by the same specialist
      nurse team.

PMID- 24672910
TI  - Are e-cigarettes a safer alternative to smoking?
AB  - Smokers appear to be using electronic cigarettes in attempts to quit but the
      products are currently unregulated. This article explores evidence regarding
      electronic nicotine delivery devices--usually known as e-cigarettes--and how this
      relates to clinical practice. It also discusses secondary care smoking cessation
      services in the light of NICE guidance.

PMID- 24672911
TI  - Blood tests and age-related changes in older people.
AB  - Many age-related changes in health can be detected in blood tests. In particular,
      renal function deteriorates with age, and this is factored in when estimating the
      glomerular filtration rate. However, some symptoms may be wrongly attributed to
      old age, while some medication can mask, exacerbate or cause problems in older
      people. This article looks at specific areas of pathology to help practitioners
      use blood tests to understand, recognise and treat diseases in older patients.

PMID- 24672912
TI  - 60 seconds with Alicia Lucas.

PMID- 24672913
TI  - Bridging the social divides.

PMID- 24672914
TI  - Voice your opinion to influence care.

PMID- 24672915
TI  - [Lucie Bedard. From Montreal to Haiti].

PMID- 24672916
TI  - [Mold in schools. A campaign to improve air quality].

PMID- 24672917
TI  - [Nothing is lost, everything is recreated! About recycled medical equipment].

PMID- 24672918
TI  - [Arthrosis of the knee].

PMID- 24672919
TI  - [Hypersexualisation].

PMID- 24672920
TI  - [Pilonidal sinus. How to promote cicatrization and prevent recurrence? Evidence
      based nursing guide].

PMID- 24672921
TI  - [Irregular bleeding. Control of side effects of combination drugs].

PMID- 24672922
TI  - [Sore throat says ahhhh!!! A targeted clinical exam].

PMID- 24672923
TI  - [Better knowledge about attracting and retaining geriatric nurses].

PMID- 24672924
TI  - [Signes "AINEES" 1. History of Mrs. Rose].

PMID- 24672925
TI  - [And if the patient requests that you wash your hands....].

PMID- 24672926
TI  - [Global warming and Northern populations].

PMID- 24672927
TI  - [Therapy compliance. Best when drug is prescribed long term].

PMID- 24672928
TI  - [Maple syrup. Health benefits].

PMID- 24672929
TI  - [Lacerations in the child. Treating without pain].

PMID- 24672930
TI  - [Postpartum depression. More frequent in major cities].

PMID- 24672931
TI  - [Consensus on ageing and anti-ageing in China (2013)].

PMID- 24672932
TI  - [Explanation and thinking of updated key points of 2013 ACC/AHA guideline on the
      treatment of blood cholesterols].

PMID- 24672933
TI  - [The agreement and differences between Chinese medicine and western medicine from
      the evolution process of heart failure].

PMID- 24672934
TI  - [A correlation research on Chinese medical syndromes of chronic heart failure and
      various complications].
AB  - OBJECTIVE: To study the correlation between various complications of chronic
      heart failure (CHF) patients and Chinese medical syndromes, thus indicating
      distribution laws of Chinese medical syndromes in various complications of CHF
      patients. METHODS: Chinese medical syndrome typing was performed in 630 CHF
      patients by cross-sectional study of the demographic data, history of present
      diseases, related information on Chinese medical four diagnostic methods, and the
      distribution of complications. Logistic regression analysis was used to determine
      the correlation of various complications of CHF patients and Chinese medical
      syndromes. RESULTS: In this study, recruited were common complications such as
      hypertension, diabetes, arrhythmia, hyperlipemia, and cerebral vascular accident,
      and so on. Main syndromes were sequenced as qi deficiency syndrome, blood stasis
      syndrome, water retention syndrome, yin deficiency syndrome, phlegm turbid
      syndrome, yang deficiency syndrome. Results of Logistic regression analysis
      indicated that correlation existed between common complications and Chinese
      medical syndromes. In CHF complicated hypertension patients, Logistic regression
      analysis showed qi deficiency syndrome and yang deficiency syndrome were
      negatively correlated with hypertension (P < 0.05). In CHF complicated diabetes
      patients, Logistic regression analysis showed phlegm turbid syndrome and water
      retention syndrome were positively correlated with diabetes (P < 0.05). In CHF
      complicated arrhythmia patients, there was no statistical difference in the
      distribution of each syndrome (P > 0.05). In CHF complicated hyperlipemia
      patients, Logistic regression analysis showed qi deficiency syndrome and water
      retention syndrome were negatively correlated with hyperlipemia (P < 0.05), while
      blood stasis syndrome, yin deficiency syndrome, and phlegm turbid syndrome were
      positively correlated with hyperlipemia (P < 0.01). In CHF complicated cerebral
      vascular accident patients, Logistic regression analysis showed qi deficiency
      syndrome and yang deficiency syndrome were negatively correlated with cerebral
      vascular accident (P < 0.01, P < 0.05). CONCLUSIONS: There existed certain
      correlations between complications of CHF and the distribution of main Chinese
      medical syndromes. It could be used as guidance for treating CHF and its various
      complications by Chinese medicine and pharmacy.

PMID- 24672935
TI  - [Effect of blood activating water relieving method on heart functions and serum
      levels of NT-proBNP in patients with heart failure with normal ejection
      fraction].
AB  - OBJECTIVE: To study the effect of blood activating water relieving method (BAWRM)
      on heart functions and serum levels of NT-proBNP in patients with heart failure
      with normal ejection fraction (HFNEF). METHODS: Sixty-four HFNEF patients were
      admitted to our hospital during January 2011 to June 2012. They were randomly
      assigned to the treatment group (32 cases) and the control group (32 cases).
      Patients in the control group received routine Western medical treatment, while
      those in the treatment group additionally took Chinese medical recipes for
      activating blood circulation and relieving water retention. Changes of Chinese
      medical syndromes, E/E', serum NT-proBNP contents were observed between the two
      groups. RESULTS: Compared with before treatment, their Chinese medical syndromes
      and E/E' were significantly improved, and serum NT-proBNP contents decreased in
      the two groups (P < 0.05). Compared with the control group, Chinese medical
      syndromes, E/E', serum NT-proBNP contents obviously decreased in the treatment
      group, showing statistical difference (P < 0.05). CONCLUSION: BAWRM was an
      effective way to improve the diastolic function of HFNEF patients and lower the
      serum level of NT-proBNP with confirmative efficacy.

PMID- 24672936
TI  - [Effect of acupuncture on acute left heart failure by PiCCO technique].
AB  - OBJECTIVE: To observe the clinical effect of acupuncture on acute heart failure
      (AHF) patients. METHODS: Totally 60 patients who were diagnosed as AHF were
      assigned to the acupuncture group and the control group, 30 in each group. Those
      in the control group received inotropic agents, preload and afterload reducing
      therapy, anti-infection and so on. Besides, those in the acupuncture group
      received needling at relative points, once daily for 5 consecutive days. The mean
      arterial pressure (MAP), heart rate (HR), cardiac index (CI), stroke volume index
      (SI), left ventricle working index (LCWI) were monitored by thermodilution pulse
      indicated continuous cardiac output (PiCCO) technique. Changes of the aforesaid
      data were compared between before and after treatment. The ICU length of stay,
      readmission rate,and the 28-day mortality were also compared between the two
      groups. RESULTS: After 5 days of the treatment, CI, SI, and LCWI increased more
      obviously (P < 0.01), HR and MAP decreased significantly (P < 0.05). Of them, CI,
      SI, and LCWI increased more obviously in the acupuncture group (P < 0.05).There
      was no obvious difference in HR or MAP between the two groups (P > 0.05).
      Compared with the first day of admission in the same group, CI, SI, and LCWI
      obviously increased in the acupuncture group from the second day (P < 0.05). HR
      started to decrease since the fourth day (P < 0.05), and MAP began to decrease
      until the fifth day (P < 0.05). CI, SI, and LCWI started to increase in the
      control group from the third day (P < 0.05); HR and MAP both began to decrease
      since the fifth day (P < 0.05). Compared with the control group, the ICU length
      of stay was obviously shortened in the acupuncture group (P < 0.05). The
      readmission rate and the 28-day mortality rate were lower than those of the
      control group (P < 0.05). CONCLUSION: The combination of acupuncture and Western
      medical therapy might strengthen acute heart failure patients' heart functions,
      elevate the therapeutic effect, and improve the prognosis.

PMID- 24672938
TI  - [Effect of Qiling Decoction combined HAART on expression levels of Treg cells and
      Th17 in HIV/AIDS patients].
AB  - OBJECTIVE: To explore the effect of Qiling Decoction (QD) combined highly active
      antiretroviral treatment (HAART) on expression levels of peripheral blood Th17
      and Treg cells in HIV/AIDS patients. METHODS: Totally 55 HIV/AIDS patients were
      randomly assigned to the treatment group (28 cases) and the combination group (27
      cases). Besides, 21 HIV negative patients were recruited as the healthy control
      group. Those in the treatment group received HARRT alone, while those in the
      combination group received HAART combined QD. The observation lasted for 24
      weeks. Meanwhile, according to peripheral blood CD4+ T cell counts before
      treatment, HIV/AIDS patients were assigned to three subgroups. For patients in
      subgroup 1, 1 cells/microL < CD4+ T cell counts < or = 100 cells/microL; For
      patients in subgroup 2, 101 cells/microL < CD4+ T cell counts < or = 200
      cells/lL; For patients in subgroup 3, 201 cells/microL < CD4+ T cell counts < or
      = 350 cells/microL. Expression of peripheral blood Th17 and Treg cells, and
      number of CD4+ T cell counts were detected using flow cytometry (FCM)in HIV/AIDS
      patients at the pre-treatment baseline, week 4, 12, and 24, as well as those in
      the healthy control group. RESULTS: Compared with the healthy control group, CD4+
      T cell counts and the baseline expression level of Th17 cells in the peripheral
      blood of HIV/AIDS patients significantly decreased, the expression level of Treg
      cells significantly increased P < 0.01). Compared with before treatment in the
      same group, CD4+ T cell counts all increased at week 4, 12, and 24 in the two
      treatment groups, showing statistical difference (P < 0.05, P < 0.01). There was
      no statistical difference in the effective rate at various CD4+ T cell levels
      between the two groups (P > 0.05). There was no statistical difference in
      expression levels of Th17 and Treg cells between the combination group and the
      treatment group at any time point (all P >0.05). The Th17/Treg ration
      significantly increased in the combination group after 24 weeks of treatment,
      showing statistical difference when compared with the treatment group (U = 2.135,
      P = 0.038). CONCLUSION: QD could improve the immune balance of Th17/Treg cells,
      which might be one of its mechanisms for improving HIV/AIDS patients' immunity.

PMID- 24672937
TI  - [Leihong granule intervened in-stent restenosis after endovascular therapy for
      lower extremity arterial occlusive diseases: a clinical observation].
AB  - OBJECTIVE: To observe the intervention effect of Leihong Granule (LG) in in-stent
      restenosis (ISR) after endovascular therapy for lower extremity arterial
      occlusive diseases (LEAOD). METHODS: Recruited 80 LEAOD patients who successfully
      underwent endovascular therapy (balloon dilation and stent implantation) were
      randomly assigned to two groups, the control group and the LG group, 40 in each
      group. Patients in the control group received basic treatment, while those in the
      LG group additionally took LG for 3 months. Plasma levels of IL-10, IL-18, CRP,
      and the intima-media thickness (IMT) of lower extremity artery were observed in
      the two groups between and after treatment. The rate of stent patency, ABI,
      intermittent claudication, rest pain, and the incidence of amputation the two
      groups were recorded and observed in the two groups. RESULTS: In the control
      group, serum levels of IL-10, IL-18, CRP, and IMT were significantly higher one
      month after surgery than before surgery (P < 0.05). There was no significant
      difference in serum levels of IL-10, IL-18, CRP, or IMT between the two groups
      before surgery (P > 0.05). These indices were obviously lower in the LG group
      than in the control group after surgery (P < 0.05). Compared with the control
      group, the incidence rates of intermittent claudication and the rest pain at 6
      months and 12 months after surgery significantly decreased (P < 0.05). The stent
      patency rate at 6 months and 12 months after surgery, and ABI were significantly
      higher than those of the control group (P < 0.05). There was no statistical
      difference in the amputation rate between the two groups (P > 0.05). CONCLUSION:
      LG might effectively improve ischemic symptoms of affected limbs possibly through
      lowering the ISR rate after endovascular therapy for LEAOD through preventing
      immunosuppressive actions.

PMID- 24672939
TI  - [Treating primary liver cancer patients by Pi-strengthening and Qi-regulating
      method: univariate and multivariate analyses of their prognoses].
AB  - OBJECTIVE: To evaluate the prognostic factors in treating primary liver cancer
      (PLC) patients by Pi-strengthening and qi-regulating method (PSQRM), thus
      providing evidence and optimizing Pi-strengthening and qi-regulating program.
      METHODS: Clinical data of 151 PLC patients treated by PSQRM at Oncology
      Department, Guangdong Provincial Hospital of Traditional Chinese Medicine from
      May 2007 to March 2009 were retrospectively analyzed. The univariate analysis was
      determined to analyze possible prognostic factors. Selected key factors were
      introduced into the COX proportional hazard model, and multivariate analysis was
      carried out. RESULTS: The 1-year survival rate was 21.85%, the median survival
      time was 6.80 months, and the mean survival time was 8.98 months. The univariate
      analysis showed that Chinese medicine (CM) syndrome types, clinical symptoms at
      the initial diagnosis, ascites, tumor types, ratios of foci, portal vein tumor
      thrombus, intrahepatic metastasis, a-fetoprotein (AFP) levels, total bilirubin
      classification, albumin classification, Child-Pugh classification, and domestic
      staging of liver cancer were significant prognostic factors (P < 0.05). The
      statistic data of multivariate analysis indicated that CM syndrome types,
      ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh
      classification, and domestic staging of liver cancer were independent factors
      influencing prognosis (P < 0.05). CONCLUSION: The prognosis of PLC treated with
      PSQRM is determined by multiple factors including CM syndrome types, ascites,
      tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification,
      and domestic staging of liver cancer.

PMID- 24672940
TI  - [Treatment of children with EB virus infection by Chinese medicine: a clinical
      study].
AB  - OBJECTIVE: To provide evidence for Chinese medical treatment of children with EB
      virus infection by exploring its clinical efficacy from multiple angles. METHODS:
      Totally 81 children patients were randomly assigned to the treatment group (46
      cases) and the control group (35 cases). Patients in the treatment group took
      Chinese medical decoction, while those in the control received intravenous
      dripping of Ganciclovir and oral administration of pidotimod. The treatment
      period for the two groups was 2 weeks. Patients were followed-up till the 12th
      week. Clinical symptoms such as fever, lymphadenopathy and hepatosplenomegaly, as
      well as lab indices such as abnormal lymphocyte percentage, EB virus antibody,
      virus DNA load, T cell subsets, immunoglobulin, and so on were observed before
      and after treatment, at week 4 and 12 of follow-ups. RESULTS: (1) The total
      effective rate at week 2 was 95.6% in the treatment group, higher than that of
      the control group (94.3%), but there was no statistical difference between the
      two groups. (2) The time for defervescence, duration of pharyngeal hyperemia,
      duration of swollen tonsils was shorter in the treatment group than in the
      control group (P<0.05). The subsidence of lymphadenopathy, hepatomegaly, and
      abnormal lymphocytes was better in the treatment group than in the control group
      (P < 0.05). (3) The positive cases of peripheral blood hetero-lymphocyte was
      significantly reduced after treatment, at week 4 and 12 of follow-ups both in the
      treatment group and the control group (P < 0.01). The expression of IgA and IgM
      decreased after treatment in the two groups when compared with before treatment
      in the same group (P < 0.05, P < 0.01). IgG in the treatment group also obviously
      decreased after treatment, at week 4 and 12 of follow-ups (P < 0.05, P < 0.01),
      while it decreased only after treatment in the control group (P < 0.05).
      Activities of AST and ALT in the treatment group and the AST activity in the
      control group were markedly improved when compared with those before treatment (P
      < 0.05). Compared with the control group, the abnormal lymphocyte positive case
      number obviously decreased in the treatment group after treatment, at week 4 and
      12 of follow-ups (P < 0.05). (4) After treatment, at week 4 and 12 of follow-ups,
      CD3+ and CD8+ significantly decreased; CD4+, CD4/CD8, and B cells significantly
      increased in the two groups, when compared with before treatment (P < 0.05). NK
      cells significantly increased more in the treatment group after treatment, at
      week 4 and 12 of follow-ups, higher than before treatment as well as the control
      group (P < 0.05). (5) EB viral DNA and EB viral CA-IgM negative conversion case
      numbers significantly increased in the two groups after treatment, at week 4 and
      12 of follow-ups (P < 0.05). Compared with the control group, EB viral DNA and EB
      viral CA-IgM negative conversion case numbers significantly increased in the
      treatment group after treatment and at week 4 of follow-ups (P < 0.05).
      CONCLUSIONS: Treatment of EB virus infection by Chinese medical treatment was
      effective. It could promote the recovery of EB viral infection, and reduce the
      risk of vicious disease after EB viral infection.

PMID- 24672941
TI  - [Effect of Qinghuang Powder combined Chinese herbs for Pi-strengthening and Shen
      reinforcing on HIF-1alpha in bone marrow mononuclear cells of myelodysplastic
      syndrome patients: an experimental research].
AB  - OBJECTIVE: To study the effect of Qinghuang Powder (QHP) combined Chinese herbs
      for Pi-strengthening and Shen-reinforcing (CHPSSR) on hypoxia-inducible factor
      1alpha (HIF-1alpha) in bone marrow mononuclear cells of myelodysplastic syndrome
      (MDS) patients. METHODS: Changes of HIF-1alpha in bone marrow mononuclear cells
      of MDS patients were detected in 25 MDS patients treated by QHP combined CHPSSR
      using flow cytometry. Meanwhile, 13 healthy subjects were recruited as the
      control group. Changes HIF-1alpha levels in various serial bone marrow
      mononuclear cells were detected. RESULTS: (1) Among the 25 patients in the
      treatment group, there were 19 patients effective and 6 patients ineffective,
      with the total effective rate being 76%. (2) Compared with before treatment,
      levels of peripheral blood WBC, Hb, PLT, and ANC significantly increased in the
      treatment group after treatment, showing statistical difference (P < 0.05, P <
      0.01). (3) Compared with before treatment, the HIF-1alpha mean fluorescence
      intensity was enhanced in bone marrow lymphocytes, monocytes, granulocytes, and
      nucleated red blood cells of the treatment group after treatment (P < 0.05, P <
      0.01). Compared with the control group, the HIF-1alpha mean fluorescence
      intensity was weakened in bone marrow lymphocytes, monocytes, and nucleated red
      blood cells of the treatment group before treatment; while it was obviously
      enhanced in granulocytes (P < 0.01). But after treatment the HIF-1alpha mean
      fluorescence intensity increased more in the granulocytes of the treatment group
      than in those of the control group (P < 0.01), but there was no statistical
      difference in bone marrow lymphocytes, monocytes, or nucleated red blood cells.
      CONCLUSION: QHP combined CHPSSR could improve HIF-1alpha levels in bone marrow
      lymphocytes, monocytes, granulocytes, and nucleated red blood cells of MDS
      patients, thus improving Hb levels of MDS patients, and improving their anemia
      and correlated symptoms.

PMID- 24672942
TI  - [Enhanced effect of guizhi plus Gegen Decoction on learning and memory disorder
      in LPS induced neuroinflammatory mice].
AB  - OBJECTIVE: To explore the potential effect of Guizhi plus Gegen Decoction (GGD)
      in improving learning and memory of lipopolysaccharides (LPS) induced
      neuroinflammatory mice and its possible mechanisms. METHODS: Totally 63 male ICR
      mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the
      model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n
      = 14), and the positive control group (n = 13). Mice were intraperitoneally
      injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in
      the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by
      gastrogavage for 4 successive weeks. Mice in the control group were
      intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of
      treatment LPS were injected 4 h before behavior test each day, and then behavior
      test was conducted in mice of each group. Effect of GGD on learning and memory of
      AD mice was observed by using open field test, novel object recognition task, and
      Morris water maze. RESULTS: Open field test showed there was no statistical
      difference in the movement time and the movement distance among all groups (P >
      0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice.
      In novel object recognition test, AD mice spent significantly shorter time to
      explore novel object after they were induced by LPS (P < 0.05), while for AD mice
      in the low and high dose GGD groups, their capacities for exploration and memory
      were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze
      showed that AD mice exhibited increased escape latency (P < 0.05) and spent much
      less time in swimming across the original platform (both P < 0.05). However, AD
      mice in the low and high dose GGD groups had obvious shortened latency and
      increased time percentage for swimming (P < 0.05, P < 0.01). CONCLUSION: GGD
      possessed certain improvement in learning and memory disorder of LPS induced AD
      mice.

PMID- 24672943
TI  - [Effect of shenxiong huayu capsule on cerebral ischemia/reperfusion injury and
      the expression of GAP43 in hippocampal CA1 of rats].
AB  - OBJECTIVE: To explore the effect of Shenxiong Huayu Capsule (SHC) on the cerebral
      ischemia-reperfusion (IR) injury and the expression of growth associated protein
      43 (GAP43) after total cerebral IR in the hippocampal CA1 region of rats.
      METHODS: Totally 100 male adult SD rats were randomly divided into five groups,
      i.e., the control group, the model group, the group A (by taking SHC once daily),
      the group B (by taking SHC twice daily), and the group C (by taking SHC thrice
      daily), 20 in each group. The total IR model was prepared by improved
      Pulsinelli's 4-vessel occlusion method. Morphological changes of the hippocampal
      CA1 region were observed by HE staining at day 1, 3, 7, and 14. The expression of
      GAP43 in the hippocampal CA1 region was detected using immunohistochemical assay
      at day 1, 3, 7, and 14. Meanwhile, the behavioral score was determined. The
      expression of GAP43 in the hippocampal CA1 region was detected using Western blot
      at day 14. RESULTS: Compared with the control group, the expression of GAP43
      increased in the model group, the behavioral score was elevated, degenerated
      neurons increased, and survival neurons decreased in the model group (all P <
      0.05). Compared with the model group, the expression of GAP-43 increased (with
      the most significant difference seen in the group C, P < 0.01), the behavioral
      score significantly decreased, degenerated neurons decreased, and survival
      neurons increased in each HSC group (all P < 0.05). Survival neurons obviously
      increased at day 14, of which, most number of survival neurons and highest
      contents of GAP43 protein could be seen in the group C, showing statistical
      difference when compared with those of the group A and the group B (P < 0.01).
      CONCLUSION: SHC had protective effect on total cerebral IR in the hippocampal
      CA1, which might be associated with increased expression of GAP43.

PMID- 24672944
TI  - [Taohong Siwu Decoction regulated functions of endothelial cells and treated
      arteriosclerosis obliterans: an experimental study].
AB  - OBJECTIVE: To discuss the effect of Taohong Siwu Decoction (TSD) in regulating
      functions of endothelial cells and treating arteriosclerosis obliterans (ASO).
      METHODS: The ASO model was prepared by using high-fat diet plus intimal injury.
      They were randomly divided into the model group (n = 10), the normal control
      group (n = 9), the low dose TSD group (group A, n = 12), the middle dose TSD
      group (group B, n = 10), and the high dose TSD group (group C, n = 9). Eight
      weeks after modeling, the limb blood perfusion was observed using laser Doppler
      flowmetry. The arterial morphology was observed using light microscope and
      transmission electron microscope. The number of circulating endothelial cells
      (CECs) was determined using Percoll density gradient centrifugation method. Serum
      levels of TNF-alpha, IL-1, ET-1, and NO were detected using double antibody
      sandwich assay of enzyme linked immunosorbent assay (ELISA). RESULTS: The ASO rat
      model was successfully established. Blood lipids levels significantly increased,
      the blood perfusion of left hind limbs significantly decreased, the number of
      CECs in the peripheral blood significantly increased, the arterial lumen was
      irregularly narrowed, the ultra-structure of vessel walls was damaged, serum
      levels of TNF-alpha, IL-1, and ET-1 significantly increased, and the serum level
      of NO significantly decreased in the model group, showing statistical difference
      when compared with the normal control group (P < 0.01). Compared with the model
      group, significant improvement in the aforesaid indices was shown in group B and
      C (P < 0.05, P < 0.01). CONCLUSIONS: The injury and abnormal functions of
      endothelial cells is an important pathological process of ASO. As an effective
      recipe for treating ASO, TSD could protect vascular endothelial cells and improve
      the secretion function of vascular endothelial cells.

PMID- 24672945
TI  - [Shen warming Pi strengthening method intervened IBS-D rats: an efficacy
      assessment].
AB  - OBJECTIVE: IBS-D rat model was established to assess the effect of Shen warming
      Pi strengthening method (SWPSM) for intervening diarrhea-predominant irritable
      bowel syndrome (IBS-D) by observing rats' general state, stool properties, AWR
      ranking, and histopathological changes. METHODS: Totally 72 rats were randomly
      divided into 6 groups, i.e. the normal group, the model group, the high, middle,
      low dose SWPSM groups, and the control group, 12 in each group. The IBS-D rat
      model was successfully established referring to AL-Chaer ED's modeling method.
      After modeling high, middle, and low dose SWPS Recipe boil-free granules were
      given by gastrogavage to rats in corresponding treatment groups. Sishen Pill boil
      free granule was given by gastrogavage to those in the control group. Equal
      volume of normal saline was given by gastrogavage to rats in the model group. The
      medication lasted for 2 weeks. Rats' general state, stool properties, abdominal
      withdrawal reflex (AWR) ranking, and histopathological changes were observed.
      RESULTS: After treatment, the general state of all rats got im- provement to
      various degrees. The improvement in the high and middle dose SWPS Recipe groups
      were superior to that in the low dose SWPS Recipe group and the control group (P
      < 0.05). There was no statistical difference in the growth rate between after and
      before treatment in each group (P > 0.05). Compared with the model group and the
      low dose SWPS Recipe group, the defecation amount within 4 h was less in the high
      and middle dose SWPS Recipe groups and the control group (P < 0.05). The Bristol
      ranking score, average ranking of loose stool, ratio of dry stool and wet stool
      were lower in the high and middle dose SWPS Recipe groups than in the control
      group and the low dose SWPS Recipe group (P < 0.05). The AWR ranking score was
      lower in the high and middle dose SWPS Recipe groups than in the control group
      when the volume of balloon dilation was 1.5 mL. There was no organic change of
      histological or morphological observation. CONCLUSIONS: High sensitive IBS-D
      model was proved to be reliable. SWPSM could reduce the quantity of stools, lower
      Bristol ranking score, average ranking of loose stools as well as ratios of dry
      stool and wet stool, contributing to reducing the high sensitivity of rats'
      visceral organs to some extent.

PMID- 24672946
TI  - [Effect of Qufeng Tongluo Recipe on expression of desmin and CD2AP proteins in
      adriamycin-induced nephropathy rats: an experimental research].
AB  - OBJECTIVE: To investigate the effect of Qufeng Tongluo Recipe (QTR) on the
      expression of desmin and CD2-associated protein (CD2AP) in adriamycin-induced
      nephropathy rats. METHODS: The adriamycin-induced nephropathy rat model was
      induced by a disposable intravenous injection of adriamycin. The model was
      successfully established after 3 weeks. Rats were then randomly divided into the
      blank control group (Group A, n =12), the model control group (Group B, n = 8),
      the small, medium, large dose QTR group (Group C, n = 8; Group D, n = 8; Group E,
      n = 8), and the positive control group (Group F, n = 8). From the fourth week
      normal saline was given to rats in Group A and Group B, QTR 1.0 g/mL, 2.1 g/mL,
      and 4.2 g/mL was respectively administered to those in Group C, D, and E.
      Prednisone 25 mg/kg was given to rats in Group F. All medication was performed by
      gastrogavage at 10 mL/kg, once daily, for 28 successive days. 24-h urinary
      protein excretion and sera biochemical indices were determined during medication.
      At the end of the experiment, ultrastructure was observed, mRNA expression of
      desmin, mRNA and protein of CD2AP were detected by Real-time PCR and Western
      blot. RESULTS: (1) Compared with Group B, 24-h urinary protein excretion
      significantly decreased in Group C, D, E, and F (P < 0.05). (2) Compared with
      Group B, Alb in Group C, D, and E increased (P < 0.05) and TC significantly
      decreased (P < 0.05). TG significantly increased in Group F (P < 0.05). (3)
      Results of electron microscope showed, compared with Group B, the morphology of
      foot cells was improved to various degrees in Groups D, E, and F, especially the
      foot process structure and the number of foot processes were significantly
      improved, which was more obviously shown in Group D and Group E. (4) mRNA
      expression of desmin, mRNA and protein of CD2AP increased in adriamycin-induced
      nephropathy rats (P < 0.05). After intervention, when compared with Group B, mRNA
      expression of desmin and CD2AP were significantly lower in Group C, D, E, and F
      (P < 0.05). (5) Compared with Group A, expression of desmin and CD2AP
      significantly increased (P < 0.05). Compared with Group B, the expression of
      desmin protein were obviously lower in Group C, D, E, and F, and the protein
      expression of desmin obviously decreased in Group D, E, and F (P < 0.05). The
      protein expression of desmin and CD2AP gradually decreased in Group C, D, and E
      (P < 0.05). Compared with Group F, the expression of CD2AP protein obviously
      increased in Group C and D (P < 0.05); the expression of CD2AP protein obviously
      decreased in Group E (P < 0.05); the expression of desmin protein was higher in
      Group C, D, and E (P < 0.05). CONCLUSION: QTR's therapeutic effect on adriamycin
      induced nephropathy rats might be achieved through altered expression of desmin
      and CD2AP.

PMID- 24672947
TI  - [Regulation of single herb pilose antler on the expression of Smad2 and Smad3 in
      the cartilage of OA rats: an experimental research].
AB  - OBJECTIVE: To observe the effect of single herb pilose antler (PA) on the
      expression of Smad2 and Smad3 in the cartilage of osteoarthritis (OA) rats.
      METHODS: One hundred 3-month old female healthy SD rats, (200 +/- 20) g, were
      recruited and routinely fed for 1 week. They were randomly divided into 5 groups,
      i.e., the low dose PA group, the high dose PA group, the normal saline control
      group, the model group, and the normal control group, 20 in each group. The model
      was prepared using classic Hulth method except the normal control group. After 6
      week modeling, the model was confirmed successful by pathologic observation. PA
      at 0.021 g/100 g and 0.084 g/1 00 g was given by gastrogavage to rats in the low
      dose PA group and the high dose PA group respectively. Normal saline was
      administered to those in the normal saline control group. No treatment was given
      to rats in the normal control group and the model group. Bilateral knee
      cartilages were harvested at week 2,4, and 6. mRNA and protein expressions of
      Smad2 and Smad3 were detected by immunohistochemical assay, fluorescent
      quantitative PCR, and Western blot. RESULTS: OA model was successfully prepared
      by pathological observation. Results of immunohistochemical assay showed that
      Smad2 and Smad3 expressed extensively in the cartilage, and located inside the
      chondrocyte membrane. Compared with the model group, mRNA expression of Smad2 and
      Smad3 obviously increased in the low dose PA group and the high dose PA group at
      week 2, 4, and 6, showing statistical difference (P < 0.05). Compared with the
      same group at week 4 after gastrogavage, mRNA expression of Smad2 and Smad3
      obviously decreased in the low dose PA group and the high dose PA group at week
      6, showing statistical difference (P < 0.05). Compared with the model group,
      protein expression of Smad2 and Smad3 obviously increased in the chondrocytes of
      the low dose PA group and the high dose PA group at week 2 and 4, showing
      statistical difference (P < 0.01). Compared with the same group at week 2 after
      gastrogavage, protein expression of Smad2 and Smad3 obviously increased in the
      low dose PA group and the high dose PA group at week 4, showing statistical
      difference (P < 0.01). Compared with the same group at week 4 after gastrogavage,
      protein expression of Smad2 and Smad3 obviously decreased in the low dose PA
      group and the high dose PA group at week 6, showing statistical difference (P <
      0.01). CONCLUSIONS: (1) The pilose antler could repair cartilages by regulating
      mRNA and protein expressions of Smad2 and Smad3. (2) Up-regulating mRNA and
      protein expressions of Smad2 and Smad3 might be one of important mechanisms for
      the pathogenesis of OA.

PMID- 24672948
TI  - [Effect of Tetramethyl pyrazine on serum levels of IL-1beta, IL-6, and IL-2, and
      NO and PGE2 in the synovial fluid of CIA rats: an experimental research].
AB  - OBJECTIVE: To observe the effect of Tetramethyl pyrazine (TMP) on the cytokines
      and inflammatory mediators in the serum and the synovial fluid of collagen
      induced arthritis (CIA)rats, and further to investigate its possible mechanisms
      for treating rheumatoid arthritis (RA). METHODS: Type II CIA rat model was
      established. Rats in the TMP group were administered with TMP at 50 mg/kg and 100
      mg/kg, once daily. Dexamethasone at 2.0 mg/kg was intramuscularly injected to
      those in the Dexamethasone treated group, once daily. Normal saline at 2 mL/kg
      was given to those in the normal control group and the model group, once daily.
      All medication was started from the 7th day, lasting to the 35th day. CIA rats'
      foot swelling degree was observed. Contents of serum IL-1, IL-6, IL-2, NO and
      PGE2in the synovial fluid were detected by radioimmunoassay and nitrate reduction
      method. RESULTS: Compared with the normal group, the foot swelling obviously
      increased, contents of NO and PGE2 in the synovial fluid were obviously elevated
      in the model group (P < 0.01). Compared with the model group, the foot swelling
      could be obviously inhibited by 100 mg/kg TMP and Dexamethasone; serum levels of
      IL-1 and IL-6 obviously decreased, serum IL-2 level obviously increased, contents
      of NO and PGE, decreased (P < 0.01). TMP 50 mg/kg could obviously inhibit the
      foot swelling of CIA rats (P < 0.01). There was no statistical difference in
      other indices (P > 0.05). CONCLUSIONS: TMP at 100 mg/kg showed obvious inhibition
      on CIA rats. Its inhibitory effect might be correlated to inhibiting activities
      of endogenous cytokines and the generation of inflammatory mediators in
      inflammation local regions, improving contents of anti-inflammation cytokines,
      and inducing the balance of the inflammatory cytokine network.

PMID- 24672949
TI  - [Effect of Shengji Huayu Recipe on the expression of MMP-3 and TIMP-1 in skin
      ulcer tissue of diabetic rats].
AB  - OBJECTIVE: To study the effect of Shengji Huayu Recipe (SHR)on the expression of
      MMP-3 and TIMP-1 in the skin ulcer tissue of diabetic rats. METHODS: The skin
      ulcer model was established in diabetic mice. Different compatibility proportions
      of SHR [the ratio of Shengji Recipe (SJR) to Huayu Recipe (HYR) = 2:1, 1:1, and
      1:2, respectively] were used to intervene. The expression of MMP-3 protein in the
      skin ulcer of diabetic rats was detected by Western blot method,and TIMP-1
      protein was detected by immunohistochemical assay. RESULTS: At each time point,
      there was no statistical difference in the blood glucose level among groups (P >
      0.05). But all of them increased significantly,when compared with those of the
      normal wound group (P < 0.01). As for the difference between after would area
      treatment and before would area treatment, better effect was obtained in the SHR
      No. 3 group and the normal ulcer group than in the diabetic ulcer model group (P
      < 0.05). Results of Western blot showed that the MMP-3 protein expression was
      higher in the SHR No. 2 group than in the SHR No.3 group (P < 0.05).
      Immunohistochemical results showed that TIMP-1 protein expression was lower in
      the SHR No. 2 group than in the SHR No. 3 group and the diabetic ulcer model
      group (P < 0.05). TIMP-1 protein expression was higherin the SHR No. 3 group than
      in the SHR No. 2 group (P < 0.01). CONCLUSION: Using SHR No.3 was conducive to
      the promotion of wound healing in early wound repair stage, and using SHR No. 2
      might be conducive to inhibiting the formation of pathological scar.

PMID- 24672950
TI  - [Synergistic interaction between melittin and chemotherapeutic agents and their
      possible mechanisms: an experimental research].
AB  - OBJECTIVE: To evaluate the effect of melittin and 5-Fu, DDP, and TXT on human
      gastric cancer cell line BGC-823 and to primarily explore their possible
      mechanisms. METHODS: Median effect analysis was employed to determine the
      interaction between melittin and 5-Fu, DDP, TXT by analyzing the relationship
      between fraction affected (FA) and the combination index (CI) acquired from the
      dose-effect curve. Expressions of chemotherapeutic agent-associated genes of BGC
      823 cells with or without treatment were measured by real-time fluorescent
      quantitative PCR. RESULTS: (1) Both melittin and chemotherapeutic agents
      inhibited the growth of BGC-823. (2) For BGC-823 cells were acted by 5-Fu
      +melittin, when FA ranged between 0.35-0.75, CI was less than 1. For BGC-823
      cells were acted by DDP + melittin, when FA ranged 0.55 or so, CI = 1; when Fa
      ranged below 0.55, CI was less than 1. For BGC-823 cells were acted by TXT +
      melittin, CI less than 1 could be seen in the whole interval. (3) After treatment
      suppressed were the expressions of chemotherapeutic agent-associated genes of BGC
      823 cells such as thymidylate synthetase (TS), excision repair cross
      complementing gene 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), beta
      tubulin III (TUBB3), and microtubule-associated protein tau (MAPT). CONCLUSIONS:
      Melittin had a synergistic effect on the cytotoxicity of chemotherapeutic agents.
      The possible mechanisms might be associated with down-regulating chemotherapeutic
      agent-associated genes.

PMID- 24672951
TI  - [Effect of Bushen Huatan Recipe on the Akt signal pathway in polycystic ovarian
      syndrome model rats with insulin resistance: an experimental research].
AB  - OBJECTIVE: To observe the effect of Bushen Huatan Recipe (BHR) on the Akt signal
      pathway in polycystic ovarian syndrome (PCOS) model rats with insulin resistance
      (IR). METHODS: Fifty Wistar female PCOS rats were randomly and equally divided
      into 5 groups, i.e., the control group, the model group, the low dose BHR group
      (5.406 g/kg), the medium dose BHR group (10.812 g/kg), and the high dose BHR
      group (21.624 g/kg), 10 in each group. Levels of fasting blood glucose (FBG) and
      insulin were detected to calculate homeostasis model assessment of insulin
      resistance (HOMA-IR). The expression of insulin receptor substrate 1 (IRS-1),
      glycogen synthetase kinase-3beta (GSK-3beta), glucose transporter 4 (GLUT-4), and
      peroxisome proliferator activated receptor (PPAR-gamma) mRNA were detected by RT
      PCR. The expression of insulin signal transduction molecular kinase B (Akt) was
      detected by Western blot. RESULTS: Compared with the control group, HOMA-IR and
      the mRNA expression of PPAR-gamma mRNA significantly increased, the mRNA
      expression of GSK-3beta, GLUT-4, and IRS-1, protein expression of Akt and p-Akt
      significantly decreased in the model group (P < 0.05). Compared with the model
      group, HOMA-IR significantly decreased, the mRNA expression of GSK-3beta, GLUT-4,
      IRS-1, and Akt protein significantly increased in the high dose BHR group (P <
      0.05, P < 0.01). The mRNA expression of p-Akt protein increased more obviously (P
      < 0.05, P < 0.01). mRNA expression of GSK- 3beta and GLUT-4 significantly
      increased (P < 0.05), while the mRNA expression of PPAR-gamma significantly
      decreased in the low and middle BHR groups (P < 0.05). The expression of p-Akt
      significantly increased in the low dose BHR group (P < 0.05). CONCLUSIONS: IR and
      abnormal insulin signal pathway existed in PCOS model rats. BHR could improve IR
      of PCOS rats, which was correlated with regulating protein expression of insulin
      signal transduction molecules.

PMID- 24672952
TI  - [A new trial of treating SAPHO syndrome: a report of one case].

PMID- 24672953
TI  - [Progress and prospective of prevention and treating aspirin resistance by
      integrative medicine].

PMID- 24672954
TI  - [Research state of promoting cervical ripening by integrative medicine].

PMID- 24672955
TI  - The unequivocal solidarity of delegates at annual delegate conferences is always
      of great delight to me.

PMID- 24672956
TI  - Ageism and moral exclusion need further discussion.

PMID- 24672957
TI  - Letter of the month: Nurses take grads under their wings.

PMID- 24672958
TI  - Human dignity and assisted suicide.

PMID- 24672959
TI  - Challenges ahead for nurse practitioners.

PMID- 24672960
TI  - Privacy concerns over medical records.

PMID- 24672961
TI  - International surrogacy: be prudent and well informed.

PMID- 24672962
TI  - ANMF Tasmania takes a new direction in education.

PMID- 24672963
TI  - Looking after the needs of children: 100 years of school nursing in Victoria.

PMID- 24672964
TI  - Compassion is not the key.

PMID- 24672965
TI  - Screening for intimate partner violence in health care settings is a contested
      arena.

PMID- 24672966
TI  - International Council of Nurses Workforce Forum meets in Dublin.

PMID- 24672967
TI  - Getting the mix right: assistants in nursing and skill mix.

PMID- 24672969
TI  - Ethics.

PMID- 24672968
TI  - Building good leadership through personal development.

PMID- 24672970
TI  - Multiple sclerosis.

PMID- 24672971
TI  - The broken cup.

PMID- 24672972
TI  - Speaking out on prostate cancer awareness.

PMID- 24672973
TI  - The impact of medication adherence on men's health.

PMID- 24672974
TI  - Creating healthy males: a lifelong journey.

PMID- 24672975
TI  - Males and eating disorders.

PMID- 24672976
TI  - Fertility: what about men?

PMID- 24672977
TI  - [Autoimmune polyendocrine syndrome type 1: clinical features and course in
      France].
AB  - Nineteen patients with autoimmune polyendocrine syndrome type 1 were identified
      in a longitudinal study conducted in northern France (Nord-Picardie-Normandie
      region, 9 million inhabitants), giving a prevalence of 1/500 000 inhabitants.
      This survey confirmed the usual onset in childhood, and the high frequency of
      candidiasis, adrenal insufficiency, alopecia and hypoparathyroidism. Broad
      phenotypic variability was observed, even within a given family. The AIRE gene
      mutations identified in these patients were closer to those observed in the
      United Kingdom than in Finland. Preliminary results of an ongoing nationwide
      survey suggest that the prevalence tends to be higher in the north.

PMID- 24672978
TI  - [Type 2 autoimmune polyendocrine syndromes (APS-2)].
AB  - Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders
      associating several organ-specific autoimmune diseases. Their high prevalence is
      due to the fact that the main manifestations of APS-2, such as thyroidal
      autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are
      common diseases. APS-2 represents a clinical model that can serve to help unravel
      the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the
      clinician, especially in poorly symptomatic forms, and may require systematic
      screening based on measurement of autoantibodies and functional markers.

PMID- 24672979
TI  - [Thyroid autoimmunity].
AB  - This review of human autoimmune thyroid disease (AITD) focuses mainly on the
      epidemiology and pathophysiology of this very common disorder, although some
      specific clinical situations are discussed. One peculiarity of AITD is the
      existence of two contrasting phenotypes: hypothyroid thyroiditis and hyperthyroid
      Graves' disease. Graves' disease is characterized by the presence of anti-TSH
      receptor antibodies capable of activating the TSH receptor, leading to thyroid
      hypertrophy and hyperfunction. In contrast, autoimmune thyroiditis progresses
      slowly, through necrosis/apoptosis of thyroid cells and their functional
      impairment. Other forms of autoimmune thyroiditis such as postpartum thyroiditis
      and silent thyroiditis are also described. The aim of this non exhaustive review
      is to provide the interested reader with basic information required for further
      investigation.

PMID- 24672980
TI  - [Importance of the postprandial phase in human health].
AB  - Humans spend more than three-quarters of their lives in the postprandial state.
      Although the link between metabolic and cardiovascular diseases and fasting lipid
      and carbohydrate metabolism has been extensively studied and illustrated on the
      basis of conventional parameters (cholesterol, triglycerides, glucose, insulin,
      etc), it is equally legitimate and important to examine the role of these
      metabolic parameters in lipotoxicity and glucotoxicity occurring during the
      postprandial phase. However, studies of postprandial excursions, peaks and 2-hour
      post-meal follow-up are not sufficient to characterize integrative metabolic
      responses during the postprandial phase. Studies of the modulation of
      postprandial hyperlipidemia and hyperglycemia, using integrated kinetic
      monitoring and stable isotope tracers, are of prime importance to highlight the
      metabolic phenomena underlying lipemic and glycemic responses and to better
      characterize their long-term metabolic consequences.

PMID- 24672981
TI  - [New insights into adipose cell biology].
AB  - Our research focuses on the molecular mechanisms controlling glycemia in healthy
      and diabetic individuals. Diabetes is now considered as a worldwide epidemic by
      WHO, and is predicted to affect several hundred million people in the near
      future. Current therapies have failed to prevent or control hyperglycemia, as
      well as the deleterious cardiovascular consequences of the disease have
      increased. New paradigms are thus needed to develop novel therapeutic strategies.
      Over the last 15 years, we have been studying the intestine as a major regulator
      of the integrated cross-talk between the brain, liver, pancreas, muscles and
      blood vessels required for glycemic control. As a first example, we identified
      that during a meal the glucose transporter GLUT2 and the intestinal hormone
      glucagon-like peptide-1 (GLP-1) are involved in glucose detection by the entero
      portal system. This was done using highly innovative experimental techniques in
      the awake free moving mouse. We then found that the enteric-vagal nervous system
      transmits this nutritional information towards the brain stem and hypothalamus,
      where leptin, neuropeptide Y and GLP-1 relay the enteric signal to control the
      endocrine pancreas (insulin-glucagon secretion), the liver (glycogen metabolism),
      the vascular system (vasodilation, arterial flow), and muscle metabolism. This
      "anticipatory metabolic reflex " is altered during diabetes and might thus
      represent a new pharmacological target. Subsequently, while investigating the
      molecular mechanisms responsible for regulating this new physiological pathway,
      we discovered that a fat-rich diabetogenic diet alters the intestinal microbiota
      and permeability. This leads to an increase in the concentration of plasma
      lipopolysaccharides (LPS), which causes metabolic endotoxemia responsible for the
      induction of low-grade inflammation that characterizes type 2 diabetes, insulin
      resistance, adipose tissue development and hepatic lipid storage. We then showed
      that bacteria can be translocated from the intestine towards tissues and the
      bloodstream. Bacterial DNA present in blood was found to be predictive of
      diabetes, 6-9 years before disease onset (patent), presenting new molecular
      targets in the microbiota-host relationship. This should enable the scientific
      community to discover new functional relationships between the genome and
      metagenome and thus to develop original preventive and therapeutic strategies for
      metabolic diseases. Four biotechnology companies have already been created on the
      basis of our findings.

PMID- 24672982
TI  - [Evaluation of an original tool for carbohydrate counting, aimed at facilitating
      the implementation of functional insulin therapy].
AB  - OBJECTIVE: Carbohydrate counting is the most difficult component of functional
      insulin therapy. We thus designed a tool to facilitate carbohydrate counting of
      meals. RESEARCH DESIGN AND METHODS: The tool consists of an illustrated directory
      (16 x 10 cm, 119 pages) presenting 389 pictures of food, classified in 12
      categories (breads, fruits, vegetables, etc.). For each photo, the name and mode
      of preparation of the foods are given, with the weight of the illustrated portion
      and its carbohydrate content as a multiple of 5 g. During the first phase of the
      study (3 days a week for 12 weeks), twelve patients with type 1 diabetes
      completed a precise food diary using a list and weight of all consumed foods. We
      were thus able to determine, for each of three meals (breakfast, lunch and
      dinner), the variability of their carbohydrate content. During the second phase
      of the study (2 weeks), the patients were given the possibility of using the
      illustrated food directory. We asked them first to estimate, from the photos, the
      global carbohydrate content of their meals, and then to weigh each food. This
      allowed us to calculate the true carbohydrate content of the meals from
      nutritional tables. RESULTS: During the first phase, the carbohydrate contents of
      breakfast, lunch and dinner were 67 +/- 29, 72 +/- 30 and 74 +/- 30 g,
      respectively (mean +/- SD, n = 12). For a given patient, the variability in the
      carbohydrate content of each meal was expressed by its standard deviation (SD).
      For the 12 patients, this variability was 18+/-+ 8, 25+/-+ 8 and 27+/-+ 11 g,
      respectively, for breakfast, lunch and dinner, and represented on the average
      about one-quarter of the total carbohydrate content. During the second phase,
      carbohydrate content, estimated by the patients using the illustrated food
      directory, correlated well with the retrospective evaluation based on nutritional
      tables (y = 0.95 x + 5 g, r2 = 0.8 ; n = 12, 235 meals). CONCLUSION: This new
      illustrated food repertory allows accurate evaluation of the highly variable
      carbohydrate content of meals, and could thus facilitate functional insulin
      therapy.

PMID- 24672983
TI  - [Challenges for clinical research on rare tumors in Europe].
AB  - Rare cancers are defined by an annual incidence below 6/100 000 new cases.
      According to this definition, 20% of malignancies in the European Union are rare
      cancers. These cancers are associated with considerable excess mortality, as they
      account for close to 30% of all cancer deaths within the E.U. This article
      reviews the specific management challenges pertaining to this group of neoplastic
      diseases, but also the research opportunities they represent for the entire field
      of oncology. The principal challenges are related to their low incidence:
      inaccurate diagnosis is frequent (up to 30% of cases), and initial management
      does always not follow clinical practice guidelines because of their limited
      diffusion in the medical community. These patients are also under-represented in
      clinical trials, because of the rarity of dedicated clinical trials in both the
      academic and industrial settings. The situation has evolved in recent years,
      however, because it is increasingly recognized that rare cancers offer major
      opportunities for clinical development. Indeed, the underlying molecular
      alterations are easier to identify than those responsible for frequent cancers.
      Other advances include the development of novel statistical methods, the
      unification of academic and industrial clinical research projects, the
      integration of patient advocacy groups in research programs, and importantly,
      paradigm shifts such as the development of tyrosine kinase inhibitors for GIST
      and other connective tissue tumors. With the increasing fragmentation of frequent
      tumors into subsets of rare tumors, as exemplified by lung cancer, many frequent
      tumors will need to be managed with approaches similar to those developed in
      recent years for rare cancers. In the age of routine molecular biology, the
      challenges of clinical research on rare tumors are thus becoming the challenges
      of all clinical research in oncology. This will required extensive multinational
      collaboration within the European Union and beyond.

PMID- 24672984
TI  - [PIP breast implants: a series of 217 explants].
AB  - On 29 march 2010, the French authorities (Afssaps) issued a health alert
      concerning breast implants manufactured by the company Poly Implant Prothese,
      because of a high rupture rate. Marketing authorization was suspended and the use
      of PIP breast implants was prohibited. In our hospital department, 630 patients
      had received these prostheses since 2001. We conducted a retrospective study of
      all patients who underwent explantation between May 2010 and January 2012,
      corresponding to 434 explanted prostheses and 217 patients, all operated on by
      the same surgeon. Median age was 42 years and the prostheses had been implanted
      an average of 4 years 7 months earlier. We found that 38 implants (8.7%) had
      ruptured, in 33 patients (15.2%). Five patients had bilateral rupture.
      Preoperative ultrasonography, performed in 166 patients, detected 30 ruptures
      that were confirmed at surgery, but missed a further 9 cases (8%). Biopsy samples
      of capsular tissue were obtained in 103 cases, revealing granulation tissue
      possibly due to silicone exposure in 33 cases, 22 of which were associated with
      intact implants. Surgical complications included three hematomas, with no
      infections. Despite the low false-negative rate of ultrasonography, we recommend
      systematic preventive explantation, owing to the risk of silicone impregnation of
      capsular tissue even in the absence of rupture.

PMID- 24672985
TI  - [From congenital glaucoma to chronic open angle glaucoma in adulthood: a clinical
      and genetic continuum].
AB  - Congenital glaucoma, a true hydrocephalus of the eye, is defined by ocular
      hypertension resulting in buphthalmos in children up to three years old, the
      elasticity of the eye wall allowing its expansion. Juvenile glaucoma in teenagers
      and chronic glaucoma in adults do not alter the external aspect of the eye, as
      the eyeball has lost its elasticity. However, chronic ocular hypertension always
      causes ischemic excavation of the optic nerve head, leading to insidious
      amputation of the visual field and, potentially, blindness. Like most
      ophthalmological disorders, the different types of glaucoma have been shown to be
      genetically determined, and alterations in several genes have been identified.
      These altered genes can be expressed more or less early in life, suggesting a
      role of modifier genes. The role of CYP1B1 alterations in classic primary
      congenital glaucoma is well known, as is the role of PITX2, FOXC1, PAX6 and LOXC1
      alterations in secondary congenital glaucoma due to iridogoniodysgenesis, and of
      MYOC alterations in the genesis of chronic glaucoma in adulthood. An outbred
      family carrying CYP1B1 mutations in the compound heterozygous state includes two
      sibs with primary congenital glaucoma and two others who developed chronic
      glaucoma in adulthood.

PMID- 24672986
TI  - [A new definition for Alzheimer's disease].
AB  - In 2007 and 2010, the International Working Group on Research Criteria for
      Alzheimer's Disease introduced a new conceptual framework that included a
      diagnostic algorithm covering early prodromal stages. There is a growing
      consensus that Alzheimer's disease (AD) should be considered as a clinical
      biological entity characterized by: i) a well-defined clinical phenotype (an
      amnestic syndrome of the hippocampal type in typical AD), and ii) biomarkers,
      especially pathophysiological biomarkers, of the underlying disease process. The
      IWG criteria created the possibility for AD to be diagnosed prior to the onset of
      dementia, and also integrated biomarkers into the diagnostic framework. Although
      these criteria were intended for research purposes, they are increasingly used in
      expert centers for early diagnosis, for example of young-onset AD and complex
      cases (posterior cortical atrophy, primary progressive aphasia, etc.), where
      biomarkers can improve the diagnostic accuracy. In this article we present this
      new approach, together with the results of ongoing validation studies and data
      obtained by a French research team.

PMID- 24672987
TI  - [Genetic control of infectious diseases: from Mendel's laws to exome sequencing].
AB  - About one-quarter of deaths worldwide (nearly 13 million per year) are still
      directly related to infectious diseases. Many new infections have emerged since
      the end of the 20th century and others will continue to do so. Human beings, like
      other animals, are not all equal with respect to their susceptibility to
      infection. Since the 1930s, numerous epidemiological studies have shown that host
      genetic factors play a major role in susceptibility and resistance to infections.
      Studies of Mendelian genetics and genetic epidemiology based on association
      studies, now using high-speed typing of anonymous polymorphic markers, can detect
      genes or loci that influence an individual's response to a particular germ.
      Different cases of susceptibility or resistance to viral, bacterial, fungal and
      parasitic infections will be used to illustrate the importance of genetic factors
      in the diagnosis of clinical manifestations and their prevention,
      characterization of host immune responses, and their influence on evolutionary
      biology. With different phenotypes associated with genetic polymorphisms, and new
      genomic techniques, the genetics of infectious diseases is entering a new era,
      raising questions of medical practice, ethics, and public and industrial
      policies.

PMID- 24672988
TI  - [Initial surgical training].

PMID- 24672989
TI  - [Heart rate variability: a cardiometabolic risk marker with public health
      implications].
AB  - Heart rate variability (HRV) is a noninvasive, practical and reproducible measure
      of autonomic nervous system function. Although the heart is reasonably stable,
      the time between two beats (R-R) can be very different. HRV is the time variation
      between two consecutive heartbeats. HRV is believed to correspond to the balance
      between the sympathic and parasympathic influences on the intrinsic rhythm of the
      sinoatrial node. HRV is influenced by lifestyle factors, including physical
      activity, eating habits, sleep pattern, and smoking. In adults, decreased HRV is
      associated with a higher risk of cardiac events, including death, and is a
      predictor of hypertension. HRV may also have predictive value for life expectancy
      and health. HRV changes due to lifestyle factors precede the onset of
      cardiovascular disorders. Measurement of HRV and its components is of major
      interest for medical practitioners and public health specialists, in order to
      predict and evaluate the risk of cardiometabolic events related to lifestyle
      factors.

PMID- 24672990
TI  - [The health impact of woodsmoke].
AB  - Biomass is an important renewable resource of primary energy. Wood burning is
      expected to expand in future as a cheap means of residential heating, especially
      in wood-producing rural areas. The health consequences of wood smoke are taken in
      account far less actively in Europe than in North America, where stringent
      limitations have been introduced, such as those of the EPA Burnwise project.
      Recently, wildfires were estimated to release 2 petagrams of carbon into the
      atmosphere worldwide, contributing to more than 300 000 deaths annually. More
      effective measures are thus needed to prevent indoor and outdoor exposure to wood
      smoke. Ultrafine particles are the biggest concern, but the volatile phase also
      contains many toxicants. Ultrafine particles are among the most dangerous
      carbonaceous particles found in polluted atmospheres. They can be identified by
      using C14, levoglucosan, crystallography and spectrometry. Any expansion of the
      use of wood as a fuel source should take into account its health impact, which is
      similar to that of fossil fuels.

PMID- 24672991
TI  - The nature and prevalence of partner psychological abuse in a national sample of
      adults.
AB  - A detailed analysis of the occurrence of serious psychological abuse (PSYAB) in
      one's "worst relationship" was solicited from a nationwide sample of adults in
      the United States. To designate that they experienced any of the psychologically
      abusive behaviors, respondents had to have perceived malignant intent by the
      perpetrator. Respondents reported significant rates of the presence and frequency
      for 14 specified categories of serious PSYAB as well as for the 42 individual
      behaviors constituting these categories (i.e., 3 per category). The 3 behaviors
      within each category frequently co-occurred even though they represented distinct
      manifestations and increasing levels of severity for that type of PSYAB. Only
      some of the behaviors demonstrated a relationship between frequency of that
      behavior in a relationship and subsequent emotional and behavioral impact.
      Neither demographics nor social desirability were strongly related to report of
      partner PSYAB.

PMID- 24672992
TI  - Using police data to measure children's exposure to neighborhood violence: a new
      method for evaluating relations between exposure and mental health.
AB  - Studies have identified a robust association between children's exposure to
      violence and their mental health. Yet, most of this research has been based on
      self-reported exposure and self-reported mental health. In this study, we used a
      new, map-based method via police data for measuring children's exposure to
      violent crime and compared it to child self-reports and parent reports of
      exposure. Results suggest that child self-reports of violence exposure may not be
      valid except for exposure to murder, but police and parent reports of violent
      crime can reveal interesting relations between violence and mental health.
      Children showed higher levels of internalizing problems in the absence of police
      reported murder and parent-reported robbery. Discussion emphasizes implications
      for measurement as well as theory building.

PMID- 24672993
TI  - Battered police: risk factors for violence against law enforcement officers.
AB  - Although we hear more about violence committed by the police, violence against
      police officers is also a major problem in the United States. Using data
      collected from the Orlando, Florida Police Department files, this study examines
      situational variables, offender characteristics, and officer demographics that
      may correlate with violence directed at law enforcement officers. Logistic
      regression results indicate that battery against one or more police officers is
      significantly more likely when multiple officers are involved, when offenders are
      women, when offenders are larger than average as measured by body mass index
      (BMI), and when offenders are known to have recently consumed alcohol. We close
      with a discussion of policy implications and directions for future research.

PMID- 24672994
TI  - Violence, victimization, criminal justice involvement, and substance use among
      drug-involved men.
AB  - This research identified three subgroups of drug-involved men based on severity
      of self-reported violence perpetration against intimate or nonintimate partners
      among a sample of 148 men selected from a subsample of participants in the
      Kentucky National Institute on Drug Abuse (NIDA) AIDS Cooperative Agreement. Men
      in the No Violence group accounted for approximately 19% of the total
      respondents, men in the Moderate Violence Severity and Extreme Violence Severity
      groups comprises 56% and 25% of the sample, respectively. Men in the Extreme
      Violence Severity group experienced significantly more psychological
      victimization as children and more frequent physical childhood abuse than did
      their peers. Men in the Extreme Violence Severity group reported having earlier
      involvement in the criminal justice system and lawbreaking behavior; they also
      reported higher frequency of marijuana and crack use. Implications for treatment
      and future research are presented.

PMID- 24672995
TI  - Testing Johnson's typology: is there gender symmetry in intimate terrorism?
AB  - Despite the vast literature on gender symmetry in the perpetration of domestic
      assault, few studies have looked specifically at both the female and male victims
      of violence. Using data from the National Violence Against Women Survey (NVAWS)
      and building on the work of Johnson and Leone (2005), this study is a comparison
      of the female and male victims of intimate terrorism (IT) and an examination of
      the effects of IT on male victims. The findings indicate that IT, as a type of
      violence, does not have the same characteristics when the victims are men. Men
      involved in a terroristic marriage are not more likely to be injured, do not miss
      work more frequently, and are not more likely to report symptoms of depression
      compared to men involved in situational couple violence (SCV). Other findings
      appear to point to gender symmetry between women and men regarding IT, although
      broad conclusions based on these findings cannot be made in the absence of a
      sufficient means to measure the level of coercion within the relationship.
      Additional research is needed with more innovative and complete measures of
      control, the defining characteristic of IT.

PMID- 24672996
TI  - Gender equality and violent behavior: how neighborhood gender equality influences
      the gender gap in violence.
AB  - Using a sample of 703 African American adolescents from the Family and Community
      Health Study (FACHS) along with census data from the year 2000, we examine the
      association between neighborhood-level gender equality and violence. We find that
      boys' and girls' violent behavior is unevenly distributed across neighborhood
      contexts. In particular, gender differences in violent behavior are less
      pronounced in gender-equalitarian neighborhoods compared to those characterized
      by gender inequality. We also find that the gender gap narrows in gender
      equalitarian neighborhoods because boys' rates of violence decrease whereas
      girls' rates remain relatively low across neighborhoods. This is in stark
      contrast to the pessimistic predictions of theorists who argue that the narrowing
      of the gender gap in equalitarian settings is the result of an increase in girls'
      violence. In addition, the relationship between neighborhood gender equality and
      violence is mediated by a specific articulation of masculinity characterized by
      toughness. Our results provide evidence for the use of gender-specific
      neighborhood prevention programs.

PMID- 24672997
TI  - Italian nurses' experience of stalking: a questionnaire survey.
AB  - A literature analysis shows that nurses are at greater risk of being stalked both
      by ex-partners and acquaintances (such as colleagues and patients) and by unknown
      stalkers. The aim of this study was to explore Italian nurses' experience of
      stalking. A copy of the Italian modified version of the Networking for Surviving
      Stalking (NSS) Questionnaire on Stalking, Beck Depression Inventory (BDI), and
      State Trait Inventory (STAI) Y1-Y2 scales were distributed to 2,000 nurses
      working in 4 Italian state hospitals. There were 765 nurses who returned the
      questionnaire (38.4%), 107 of whom had been victims (14.0%). On average, victims
      had been stalked for more than 12 months by an acquaintance (41.1%), whose
      behavior included unwanted communications, following, control, and threatening
      behavior. The coping strategies used most involved offensive and interactional
      tactics. Stalking has both emotional and physical consequences for victims,
      although depression levels were not as high as we expected (BDI M = 11.05, SD =
      8.84; STAI Y1 M = 42.11, SD = 11.75; STAIY2 M = 44.04, SD = 12.90). The need to
      adopt legal, organizational, and individual strategies is also discussed.

PMID- 24672998
TI  - Exploring the experiences of violence among individuals who are homeless using a
      consumer-led approach.
AB  - Homelessness increases vulnerability to violence victimization; however, the
      precise factors associated with victimization and injury are not clearly
      understood. Thus, this study explores the prevalence of and characteristics
      associated with violence victimization among homeless individuals by surveying
      approximately 500 individuals experiencing homelessness in 5 cities across the
      United States. Our findings reveal that nearly one-half of our sample reported
      experiencing violence and that prolonged duration of homelessness (greater than 2
      years) and being older increased the risk of experiencing a violent attack. In
      addition, increased length of homelessness and female gender predicted
      experiencing rape. Women were also significantly more likely to know one's
      perpetrator and experience continued suffering after a violent attack. We
      conclude that certain subpopulations within the homeless population are at an
      increased risk for victimization and, subsequently, require added protective
      services; implications for health care and policy recommendations are also
      discussed.

PMID- 24672999
TI  - A new metaphor for speaking of trauma: the toroidal island model.
AB  - This article provides a model for speaking of trauma based on the author's
      ethnographic and clinical experiences mainly in Japan. It is often assumed that a
      person with more serious trauma has the right and ability to speak out. But those
      who are at the center of trauma and unable to survive cannot testify. Based on
      this notion, a toroidal island (TI) model, shaped like a doughnut with a
      landlocked inner sea, is developed. The voices come from the survivors on the
      inner slope and from the supporters on the outer slope on the island. The model
      integrates various aspects of trauma by employing metaphors of "gravity" for
      symptoms of trauma, "wind" for interpersonal conflicts, and "water level" for
      intelligibility of the speech and its social recognition. It addresses the social
      construction of trauma and shows the relativistic nature of when and how some
      traumatic experiences are recognized. Clinical and social activity to raise
      awareness of unrecognized trauma can be analogized to a process of creating a TI.
      By defying gravity and wind and lowering the water level, they keep the voices of
      the traumatized from being silenced and allow their suffering to be alleviated.

PMID- 24673000
TI  - Associations and experiences observed for family and nonfamily forms of violent
      behavior in different relational contexts among Swedish men and women.
AB  - The aim of this study was to examine how lifetime experiences of different types
      of violent behavior as well as violence by different kinds of perpetrators
      overlap, and to investigate the co-occurrence of experiences of violent behavior
      by kind of perpetrator. This was done among both sexes in both a random sample
      from a county population (women n = 1,168, men n = 2,924) and a clinical sample
      (women n = 2,439, men, n = 1,767) in Sweden. More than 1 kind of perpetrator was
      reported by 33%-37% of female and 22%-23% of male victims of some kind of
      violence, whereas 47%-48% of female and 29%-31% of male victims reported more
      than 1 kind of violence. The reporting of 2 or 3 kinds of perpetrators was
      associated with the reporting of experiences of more than 1 kind of violent
      behavior. Health care providers must be trained to recognize the overlap of
      violent victimization and help prevent further victimization of those who already
      have such experiences.

PMID- 24673001
TI  - Revisiting the effects of self-protective behaviors on the risk of injury in
      assaults against women.
AB  - Using data from the National Crime Victimization Survey (NCVS; 1992-2005), we
      closely examined the effects of victims' self-protective actions on the risk of
      injury among female nonsexual assault victims. Building on previous research, we
      focused on 3 important methodological and conceptual issues: (a) gradational
      coding of the 16 different NCVS self-protective actions, (b) separate analyses of
      serious injuries, and (c) the victim-offender relationship. Our analyses
      demonstrated that the risk of injury was strongly and positively associated with
      the degree of forcefulness of self-protective actions. Furthermore, the
      likelihood of victim injury was inversely related to the relational distance
      between the victim and the offender.

PMID- 24673002
TI  - [Myocarditis in children--a diagnostic and therapeutic challenge].
AB  - Viral infections are the most common causes of myocarditis in children. Chronic
      myocardial injury may develop following an immune or autoimmune reaction
      triggered or maintained by an infection, or can be part of a systemic autoimmune
      disease. Although many of the children having developed myocarditis are
      symptomless, initial symptoms may include cardiac insufficiency, arrhythmias and
      sudden death. The diagnosis requires a clinical suspicion as well as laboratory
      and imaging studies. Recovery from myocarditises often takes place spontaneously,
      but some result in the development of dilated cardiomyopathy (DCM).

PMID- 24673003
TI  - [Research performed at a university hospital is worthwhile].
AB  - To elucidate the effects of scientific research performed within the Hospital
      District of Helsinki and Uusimaa (HUS) on the treatment of patients, we studied
      the contribution of HUS to treatment recommendation work, preparation of
      textbooks and manuals, national or international expert assignments, as well as
      by using focused questionnaires. In our surveys, 82% of the research group
      leaders reported that their research has resulted in changes in clinical work.
      The total number of changes was approximately 700. More than 80% of the directors
      of medical services judged that research work had improved the expertise of the
      personnel as well as the effectivity and productivity of the hospital.

PMID- 24673004
TI  - [Diagnosis and treatment of appendicitis].
AB  - The diagnosis of appendicitis is based on the typical symptom picture and
      clinical findings. Laboratory studies, in which leukocytosis and an increased
      neutrophil count are typical findings, can be used in support of the diagnosis. A
      high CRP level indicates a complicated disease. A large proportion of
      appendicitis patients do not exhibit a typical symptom picture, and imaging is in
      these cases required to confirm the diagnosis. In cases of uncertain clinical
      diagnosis, appendicitis can be found fairly reliably by using computed tomography
      scanning of the abdomen. Urgent appendectomy is the current care for
      appendicitis.

PMID- 24673005
TI  - [Update in current care guidelines: acute kidney injury].
AB  - Acute Kidney Injury is an increasing problem. Prevention is based on early
      detection of risk patients, avoidance of nephrotoxic medications, and adequate
      fluid therapy with crystalloid solutions. Mortality does not differ between
      intermittent and continuous renal replacement therapy. Dose above 22 ml/kg/h does
      not decrease mortality. A working group appointed by the Finnish Medical Society
      Duodecim, the Finnish Society of Anaesthesiologists, Subdivision of Intensive
      Care Medicine and the Finnish Society of Nephrology

PMID- 24673006
TI  - [Unconsciousness].
AB  - Unconsciousness is a directly life-threatening condition that requires immediate
      action to reveal its cause. The cause of unconsciousness is usually metabolic or
      toxic and in the rest of the cases structural and intracranial. Unconsciousness
      results from a disturbance of function of either the reticular activating system
      or both cerebral hemispheres. Treatment of an unconscious person begins with the
      confirmation of vital functions. Special attention is paid on head and neck
      injuries, meningism, pupillary inequality and papillary stasis. Both radiological
      and laboratory investigations are usually required. Owing to its quickness, CT
      scan of the head is the basic neurological examination, adequately revealing the
      common intracranial causes. Treating an unconscious patient calls for the
      complete range of a physician's expertise. Determined action and knowledge of
      common and treatable diseases will, however, bring the situation under control.

PMID- 24673007
TI  - [Can you recognize a candidate for thrombolytic treatment of ischemic stroke?].
AB  - Intravenous thrombolytic treatment of ischemic stroke is the central treatment
      option in patients presenting with acute stroke symptoms. The thrombolytic
      treatment chain is initiated in the emergency services call center immediately
      after stroke is suspected. Even one point on the FAST scale mandates urgent
      transport for assessment of thrombolytic treatment. The FAST test identifies
      eight out of ten strokes, and the stroke diagnosis is confirmed in the emergency
      department with immediate imaging. The most significant groups of differential
      diagnosis include epileptic seizures, migraine, incoherence associated with
      infection, syncope and psychiatric states. There is every reason to hasten the
      confirmation of diagnosis and implementation of treatment at all stages of the
      treatment chain.

PMID- 24673008
TI  - [Headache patient at the emergency call service].
AB  - Headache is a common symptom, sometimes concealing a severe illness. It is the
      primary task of the doctor on call to find out whether the headache is a symptom
      of serious incidence needing diagnosis urgently to prevent death or permanent
      disability. Dangerous headaches are associated with easily remembered warning
      signs: sudden onset, the first or worst headache in life, disturbance of
      consciousness in connection with the headache, onset at age over 50, worsening of
      headache in the lying position, a neurological deficit associated with the
      headache, or papilledema.

PMID- 24673010
TI  - [Neurologic clinical examination at the emergency department].
AB  - The aim of emergency neurologic clinical examination is to recognize or exclude
      any problems of the nervous system requiring immediate action. The nature of the
      examination depends on the operational environment. At the emergency call service
      of a community health center a decision must first be made on whether the
      patient's problem is a neurologic one at all, followed by an assessment of the
      need of possible emergency actions and referral to hospital. At the specialized
      care emergency service the questions will more widely focus on the diagnostic
      examination strategy, selection of treatment methods and their optimally
      scheduled use in an appropriate operational environment.

PMID- 24673009
TI  - [Vertigo from the practitioner's standpoint].
AB  - One third of the population suffer from vertigo at some stage of their life. Some
      of its causes are harmless, some life-threatening, some will resolve
      spontaneously and some never. Vertigo is divided into four main types: vertigo,
      syncope, disturbance of balance and nonspecific vertigo. Medical history is the
      most important method of examination and leads to diagnosis in two out of three
      cases. Attempts are always made to provoke the sensation of vertigo and the
      possible nystagmus during the consultation. The success of the specific treatment
      in accordance with the primary cause determines the patient's prognosis.

PMID- 24673011
TI  - Developing mental health services in Nepal.

PMID- 24673012
TI  - All roads lead to productivity--but at what cost?

PMID- 24673013
TI  - "The clouds are gathering...".

PMID- 24673014
TI  - Nurses feel the heat.

PMID- 24673015
TI  - Surviving night shift.

PMID- 24673016
TI  - Recommended fasting practices for adult, low risk patients prior to elective
      procedures requiring general anaesthesia.

PMID- 24673017
TI  - Media manipulation and the euthanasia debate.

PMID- 24673018
TI  - Malnutrition and the role of nurses: a nursing issue.

PMID- 24673019
TI  - Using tablet technology to improve interactions in residential facilities.

PMID- 24673020
TI  - Impact of aggression.

PMID- 24673021
TI  - The importance of culture and spiritual life for older people: a practice
      development initiative.

PMID- 24673022
TI  - A journey--but where is the start line?

PMID- 24673023
TI  - Innovation in aged care leadership: overcoming workforce and care quality issues?

PMID- 24673024
TI  - Management of aged care residents in the emergency department.

PMID- 24673025
TI  - Nursing people with dementia in hospital.

PMID- 24673027
TI  - Therapeutic seals come to Townsville.

PMID- 24673026
TI  - Online tool gives access to residential aged care research.

PMID- 24673028
TI  - Osteoarthritis: more than a stiff joint.

PMID- 24673029
TI  - Spiritual health care.

PMID- 24673030
TI  - Pressure area care has always been essential.

PMID- 24673031
TI  - Adequately addressing borderline personality disorder.

PMID- 24673032
TI  - A big year ahead.

PMID- 24673033
TI  - Hand safety for specialty crop production workers: a pilot study investigating
      frequencies of minor open-wound hand injuries and presence of pathogenic
      bacteria.
AB  - The purpose of this study was to quantify the presence of minor open-wound hand
      injuries in addition to Salmonella, Staphylococcus aureus, coliforms, and
      Escherichia coli on the hands of farm workers who hand-harvest fruit crops in
      Utah. Data collection was conducted on four farms without USDA Good Agricultural
      Practices (GAP) certification and on two farms with GAP certification. This study
      identified essential safety issues that need to be addressed for improving the
      effectiveness of safety training for migrant farm workers. Farms that have a food
      safety audit program in place are less likely to have farm workers exposed to
      pathogenic bacteria and open-wound injuries to their hands. High frequency of S.
      aureus may indicate a potentially higher risk for wound infection within this
      worker population. This could lead to infections that are resistant to the
      antibiotics commonly used to treat ordinary staph infections, resulting in
      greater work loss time and medical expenses for these workers. Higher frequencies
      of bacterial presence on workers' hands on non-certified farms indicate a need to
      identify essential practices to improve worker hygiene habits and on-farm
      management practices to promote healthy hygiene. Open-wound injuries to migrant
      farm workers during hand-harvesting could create additional health problems with
      the possibility of infection and the spread of diseases. Continued research is
      needed to understand workers' acceptance of these injuries and barriers to
      personal protection.

PMID- 24673034
TI  - Narrow-track wheeled agricultural tractor parameter variation.
AB  - Despite a general consensus among farmers, manufacturers, and researchers that
      wheeled agricultural tractor design has changed over time, there is little
      published evidence. There is debate as to whether the standardized rollover
      protective structure (ROPS) energy and force requirements, based on a tractor
      reference mass and pertaining to studies conducted more than 40 years ago, are
      appropriate for modern tractors. This article investigated the physical
      parameters of 326 modern narrow-track tractors, measured according to OECD Code 6
      over 16 years (1993 to 2008 inclusive): 252 (-77%) were fixed-chassis tractors
      and 74 (-23%) were articulated. To understand the significance of design changes,
      the data were analyzed with respect to time and as a function of tractor mass.
      Articulated and fixed-chassis data were treated separately. The time data allowed
      qualitative analysis, while the mass data allowed quantitative analysis. The
      parameters show some changes over time and clearly indicate differences between
      articulated and fixed-chassis types. The parameter changes, along with the
      differences between types, may have important safety ramifications for ROPS
      energy absorption requirements, and these aspects are discussed. Regression lines
      with R2 values were fitted to the mass-related data for fixed-chassis and
      articulated tractors to determine the suitability of fit. The mass relations also
      displayed differences between fixed-chassis and articulated tractors. Thus, the
      most significant recommendation from this study is that the standardized testing
      procedure for narrow-track wheeled agricultural tractor category should be split
      into two groups: fixed-chassis and articulated.

PMID- 24673035
TI  - Hydrogen sulfide gas emissions during disturbance and removal of stored spent
      mushroom compost.
AB  - Spent mushroom compost (SMC) is a by-product of the mushroom industry that is
      used as an agricultural fertilizer. In Europe, SMC storage and use are governed
      by EU Nitrates Directive 91/676/EEC to protect waterways against pollution by
      nitrates. A health and safety risk was identified during the removal of stored
      SMC for land application, as the stored SMC released high levels of toxic H2S gas
      into the atmosphere when disturbed. In this study, emissions of H2S were
      monitored at two outdoor and two indoor locations where stored SMC was being
      removed for land application. A repeating peak-trough pattern of H2S emissions
      was detected at all sites, with peaks corresponding to periods of active
      disturbance of SMC. The highest H2S concentrations (10 s average) detected at the
      SMC face were, respectively, 680 and 2083 ppm at outdoor sites 1 and 2, and 687
      and 89 ppm at indoor sites 3 and 4. Higher concentrations of H2S were released
      from older SMC compared to newer material. Indoor-stored SMC had lower moisture
      content (53% to 65%) compared to outdoor-stored material (66% to 72%), while the
      temperature of indoor-stored SMC was higher (33 degrees C to 51 degrees C)
      compared to outdoor-stored material (24 degrees C to 36 degreees C). The current
      short-term exposure limit (STEL) of 10 ppm was exceeded at all sites except site
      4, which was smaller than the other sites, indicating a significant health and
      safety risk associated with working in the vicinity of stored SMC when it is
      being actively disturbed. Results suggest that SMC stored under cover in small
      heaps (600 m3) emits less H2S during disturbance and removal compared to SMC
      stored outdoors in large heaps (> 1500 m3). This should be taken into
      consideration in the design, construction, and management of SMC storage
      facilities. Health and safety protocols should be in place at SMC storage
      facilities to cover the risks of exposure to toxic H2S gas during disturbance of
      stored SMC.

PMID- 24673036
TI  - Hydrogen sulfide gas emissions in the human-occupied zone during disturbance and
      removal of stored spent mushroom compost.
AB  - Hydrogen sulfide (H2S) gas levels were monitored in the human-occupied zone at
      four spent mushroom compost (SMC) storage sites during removal of SMC for
      application on agricultural land. During SMC removal operations, H2S gas monitors
      were mounted on the outside of the tractor positioned at the SMC periphery, and
      worn by individual tractor drivers. The highest H2S concentrations (10 s average)
      detected outside the tractor, at the SMC periphery, and for the tractor driver
      were, respectively, 454, 249, and 100 ppm for the outdoor sites and 214, 75, and
      51 ppm for the indoor sites. The highest short-term exposure values (STEV over a
      15 min period) outside the tractor at the SMC periphery, and for the tractor
      driver were 147, 55, and 86 ppm for the outdoor sites and 19, 9, and 10 ppm for
      the indoor sites. The values exceeded the current maximum permissible
      concentration limit of 10 ppm for all the sites except for the SMC periphery and
      tractor driver at the indoor sites. Results suggest that H2S levels detected at
      indoor storage sites during SMC removal are lower compared to outdoor storage
      sites. Results indicate that there is a substantial health and safety risk
      associated with working in the vicinity of stored SMC when it is being disturbed
      and removed for land application, and that the risk is great for the tractor
      driver. This article discusses possible control measures and lists
      recommendations to reduce the risks.

PMID- 24673037
TI  - Therapists' experience of loss: an interpretative phenomenological analysis.
AB  - This qualitative study aimed to explore therapists' experiences of loss. Semi
      structured interviews were conducted with 6 therapists and the data were
      subjected to interpretative phenomenological analysis. Three master themes
      emerged from the analysis: (a) the grieving therapist, (b) hindrances in
      grieving, and (c) the impact of loss on therapeutic work. Therapists talked about
      their grief and elaborated on how they coped with their bereavement. Hindrances
      in their grief were reported, emerging both from others' stance and from their
      own. Participants found that their experience of loss was related to both
      challenges and advancements in their therapeutic work.

PMID- 24673038
TI  - Talking through the dead: the impact and interplay of lived grief after suicide.
AB  - In the aftermath of suicide, grief becomes a multi-faceted experience.
      Traditionally, this grief was silenced where the shame attached to suicide
      invalidated a person's need for expression. Even now, it can be difficult for
      people to fully articulate their grief, let alone find an empathetic audience.
      How do we examine this grief to more clearly hear the voices of the bereaved, and
      to better understand how to support those who are grieving a suicide death?
      Indeed, the ripple of suicide grief touches more than those traditionally
      considered to be impacted by the death. Whole communities can be affected and it
      cannot be presumed that researchers do not have their own lived experiences of
      suicide bereavement. In this way, the newly-opened discourse around the
      experience of suicide grief needs to be dissected within more practical and
      appropriate research. A balance needs to be created in research where the voices
      of grief can be included but the experiential context understood and respected.

PMID- 24673039
TI  - "Widowerhood": masculinities and spousal loss in the late-1960s.
AB  - This study examined the distinctly gendered experiences of young widowers. Using
      qualitative longitudinal data from the 1960's Harvard Bereavement Study, we
      evaluated the interview transcripts of 19 widowers (median age = 38) who had been
      interviewed 3 weeks, 8 weeks, 13 months, and 2-4 years after the wife's death.
      Our findings indicate that the off-time spousal loss ruptured the ontological
      security that marriage provided and created two types of difficult situations for
      the widowers. Coping with deep sadness and grief, the men divulged their unspoken
      dependency on their marriage and on their late wife. They also struggled as
      single fathers, especially if they tried to singlehandedly care for their
      children. Becoming an off-time widower in the 1960s compelled the men to reclaim
      their masculine identity. Men's identity-rebuilding strategies involved promptly
      returning to work, and many men began dating and repartnering to recoup the
      normalcy of being married.

PMID- 24673040
TI  - An exploratory study of death anxiety and trainees' choice of theoretical
      orientation.
AB  - This study investigated the association between therapist-trainees' death anxiety
      and their preference for "objective" (i.e., quantitative and rational) over
      "subjective" (i.e., experiential and symbolic) theoretical orientations. In this
      correlational investigation, 303 clinical psychology and counseling trainees at a
      Midwestern school of professional psychology completed instruments assessing
      their fear of personal death and their endorsement of superordinate dimensions of
      psychotherapy orientations. As hypothesized, trainees who reported higher levels
      of death anxiety displayed a stronger preference for objective over subjective
      orientations, a relationship that was found in post-hoc analyses to be
      particularly salient for male trainees. These findings suggest that trainees'
      death anxiety, and their attempts to control it, could influence their choice of
      a theoretical orientation. Potential implications for training institutions are
      discussed.

PMID- 24673041
TI  - Reading between the lines: a comparison of 480 German and Dutch obituaries.
AB  - Obituaries do not only announce the death of a significant other but also provide
      insights into how a society deals with death according to the norms governing the
      rituals of individuals within that society. This study aimed at investigating
      possible differences between German and Dutch obituaries, specifically in terms
      of visual and textual elements, information about the deceased, and funeral
      ceremony-related information. Data used to address the research questions were
      the contents of 240 German and 240 Dutch obituaries published in 10 different
      newspapers (6 in Germany, 4 in The Netherlands). Results of this study show that
      statistically significant differences between German and Dutch obituaries exist.
      While German obituaries use illustrations more than Dutch ones, Dutch obituaries
      provide more information, in general, than their German counterparts. The types
      of deceased-related information on German and Dutch obituaries also vary
      significantly. Moreover, Dutch obituaries provide more funeral ceremony-related
      information than German obituaries.

PMID- 24673042
TI  - [Introduction of advanced research philosophy to promopt leaping development of
      academic subject].

PMID- 24673043
TI  - [Efficacy comparison of different points combination in the treatment of
      menopausal insomnia: a randomized controlled trial].
AB  - OBJECTIVE: To compare the efficacy of different points combination in the
      treatment of menopausal insomnia. METHODS: Ninety-six cases of menopausal
      insomnia were randomized into 3 groups, Xinshu (BL 15), Shenshu (BL 23),
      Sishencong (EX-HN 1), Shenmen (HT 7), Sanyinjiao (SP 6) were chosen in the
      restore interaction between the heart and the kidney group (group A, 32 cases);
      Zhaohai (KI 6), Jiaoxin (KI 8), Shenmai (BL 62), Pucan (BL 61) were chosen in the
      acupuncturing qiao mai group (group B, 32 cases); auricular Shenmen (TF4) and
      sensitive spot at the distribution area of auricular vagus nervus were chosen in
      the ear acupuncture group (group C, 32 cases). Six days made one session and the
      treatments were finished after 4 courses. The polysomnography (PSG) and
      Pittsburgh sleep quality index (PSQI) were employed before and after treatment to
      evaluate the alleviation of insomnia. RESULTS: The parameters of the sleep
      latency (SL), rapid wave sleep latency (RL) and sleep efficiency (SE) were
      significantly improved in the three groups, and the differences were
      statistically significant (P < 0.05, P < 0.01). The SL and awaking time (AT) in
      group C [SL (401.08 +/- 16.54) min and AT (4.87 +/- 2.64) times] were
      significantly superior to those in the other two groups [SL (50.36 +/- 18.47)
      min, (54.87 +/- 20.92) min, AT (5.98 +/- 2.11) times, (6.13 +/- 3.04) times, all
      P < 0.05]. The S(3+4) (%) in group C was also significantly higher than those in
      the other two groups (both P < 0.05). It was indicated by PSQI that the sleep
      quality of group C (0.78 +/- 0.12) was significantly superior to that in group B
      (1.32 +/- 0.29), the total score and cured and markedly effective rate in group C
      [(4.34 +/- 1.43), 68.8% (22/32)] were superior to those in group A [(7.48 +/-
      3.09), 53.1% (17/32), both P < 0.05]. CONCLUSION: Ear acupuncture has a better
      curative effect than the restore interaction between the heart and the kidney
      group and acupuncturing qiao mai group, it is worth of being promoted.

PMID- 24673044
TI  - [Post-stroke dysphagia in chronic stage treated with magnetic-ball sticking
      therapy at the auricular points: a randomized controlled trial].
AB  - OBJECTIVE: To assess the effectiveness and safety on post-stroke dysphagia in
      chronic stage treated with magnetic-ball sticking therapy at the auricular
      points. METHODS: Ninety cases of post-apoplexy dysphagia in chronic stage were
      randomized into an auricular points group and an acupuncture group. In the
      auricular points group, the magnetic-ball sticking therapy was applied to
      subcortex (pizhixia, AT4), brainstem (naogan, AT(3,4i)), mouth (kou, CO1), cheek
      (mianjia, LO(5,6i)), tongue (she, LO2) and throat (yanhou, TG3) on one ear each
      time, and were changed on the other ear once every 3 days. In the acupucnture
      group, acupuncture was applied to Feng-chi (GB 20), Yifeng (TE 17), Shanglianquan
      (Extra), Jinjin (EX-HN 12), Yuye (EX-HN 13), Shuigou (GV 26) and Tongli (TH 5),
      etc. The needles were retained for 30 min in each treatment. The treatment was gi
      yen once a day in the two groups and the treatment of 6 days made one session.
      There was 1 day at an interval among the sessions. Totally, 3 sessions of
      treatment were required. The video fluoroscopic swallowing study (VFSS) was
      performed for 4 kinds of food with different properties and shapes in each
      patient. The main indices were Rosenbek penetration-aspiration score, oral
      retaining score and throat-retaining score. The efficacy, and the incidences of
      aspiration pneumonia and malnutrition were compared between the two groups. The
      nutrition indices were compared before and after treatment between the two
      groups, such as the skinfold thickness of triceps brachii muscle, serum albumin
      and peralbumin. RESULTS: In 21 days of treatment, in the auricular points group,
      the 1 mL liquid loversol Rosenbek penetration-aspiration score (1.51 +/- 0.69),
      oral-retaining score (1.17 +/- 0.38) and throat-retaining score (1.30 +/- 0.66)
      were all lower than those (2.51 +/- 0.67, 1.63 +/- 0.72, 1.67 +/- 0.7) in the
      acupuncture group separately. The 10 mL liquid loversol Rosenbek penetration
      aspiration score (2.27 +/- 0.65), oral-retaining score (1.60 +/- 0.50) and throat
      retaining score (1.49 +/- 0.51) were all lower than those (4.19 +/- 0.73, 2.30 +/
      0.51, 2.41 +/- 0.50) in the acupuncture group separately. The 10 mL paste
      loversol Rosenbek penetration-aspiration score (1.68 +/- 0.81), oral-retaining
      score (1.11 +/- 0.31) and throat-retaining score (1.10 +/- 0.31) were all lower
      than those (3.91 +/- 0.68, 1.63 +/- 0.76, 1.60 +/- 0.76) in the acupuncture group
      separately. The 1/4 cake-form loversol Rosenbek penetration-aspiration score
      (2.60 +/- 0.65), oral-retaining score (1.40 +/- 0.50) and throat-retaining score
      (1.74 +/- 0.49) were all lower than those (4.14 +/- 1.10, 2.40 +/- 0.73, 2.30 +/-
      0.83) in the acupuncture group separately. The incidence of aspiration pneumonia
      was 14.9% (7/47) in the auricular points group, which was lower than 55.0%
      (22/40) in the acupuncture group (P < 0.01). The incidence of malnutrition was 8.
      5% (4/47) in the auricular points group, which was lower than 50.0% (20/40) in
      the acupuncture group (P < 0.01). In 21 days of treatment, the results of the
      skinfold thickness of triceps brachii muscle and serum albumin in the auricular
      points group were better than those in the acupuncture group (both P < 0.05).
      CONCLUSION: The magnetic-ball sticking therapy at auricular points achieves the
      definite efficacy on post-stoke dysphagia in chronic stage and decreases the
      incidences of aspiration pneumonia and malnutrition. The efficacy of this therapy
      is better than acupuncture.

PMID- 24673045
TI  - [Impacts of moxibusiton on pain in the dressing change after perianal abscess
      surgery: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the therapeutic effect on pain in the dressing change
      after perianal abscess surgery treated with warm suspending moxibustion at
      Changqiang (GV 1). METHODS: One hundred and sixty patients were randomized into a
      moxibustion group and a far-infrared therapy group, 80 cases in each one. In the
      moxibustion group, the warm suspending moxibustion at Changqiang (GV 1) was
      applied. In the far-infrared therapy group, the infrared ray was radiated at
      Changqiang (GV 1). The treatment started in 10 min after dressing change in the
      two groups. Totally, 8 treatments were required. The time requirement being equal
      to or less than 2 score in the assessment face scale (AFS), the case number of
      pain relief in 10 min after treatment and the intention of the two therapies
      after everyday dressing change were observed in the patients of the two groups.
      RESULTS: In the moxibustion group, the time of pain relief was shorter than that
      of the far-infrared therapy group [(11.5 +/- 3.9) min vs (17.8 +/- 3.8) min on
      the 1st day; (9.4 +/- 3.6) min vs (15.2 +/- 4.3) min on the 2nd day; (7.8 +/-
      2.7) min vs (14.3 +/- 3.2) min on the 3rd day; (6.4 +/- 3.3) min vs (10.5 +/-
      2.9) min on the 4th day; (5.9 +/- 2.9) min vs (11.2 +/- 1.9) min on the 5th day;
      (5.3 +/- 2.2) min vs (8.8 +/- 2.3) min on the 6th day; (5.4 +/- 1.8) min vs (9.2
      +/- 2.1) min on the 7th day; (5.1 +/- 1.4) min vs (9.5 +/- 2.6) min on the 8th
      day, all P < 0.05]. The case numbers of pain relief in 10 min after treatment
      were 74 cases, 75 cases, 77 cases and 78 cases from the 1st to the 4th day
      separately in the moxibustion group, which were much more than 63 cases, 65
      cases, 68 cases and 69 cases in the far-infrared therapy group (all P < 0.05).
      The treatment intention scores in the moxibustion group were better than those in
      the far-infrared therapy group (all P < 0.05). CONCLUSION: The warm suspending
      moxibustion at Changqiang (GV 1) relieves pain rapidly in the dressing change of
      much more patients after perianal abscess surgery in much shorter time as
      compared with the far-infrared therapy. Moreover, the patients have more
      expectation to be treated with moxibustion therapy.

PMID- 24673046
TI  - [Seventy-eight cases of humeral epicondylitis treated by pricking and cupping
      combined with moxibustion].

PMID- 24673047
TI  - [Efficacy analysis on type 2 diabetes mellitus treated with acupuncture in
      females].
AB  - OBJECTIVE: To evaluate the efficacy and the relevant effect factors of
      acupuncture for type 2 diabetes mellitus (T2DM) in females. METHODS: Of 83 female
      patients of T2DM, 49 cases were deficiency of kidney yin syndrome and 34 cases
      were yin and yang deficiency syndrome. Acupuncture was adopted and the acupoints
      were selected according to the syndrome differentiation. In kidney yin deficiency
      syndrome, Taixi (KI 3), Shenmen (HT 7), Taichong (LR 3) and Sanyinjiao (SP 6),
      etc. were selected. In yin and yang deficiency syndrome, Shenshu (BL 23), Pishu
      (BL 20), Yishu (Extra) and Jingmen (GB 25), etc. were selected. In 3 courses of
      treatment, the changes in fasting plasma glucose (FPG), fasting insulin (FINS),
      insulin sensitivity index (ISI), insulin resistace index (Homa-IR), index of
      islet beta-cell function (Homa-beta), total cholesterol (TC), triglyceride (TG),
      low density lipoprotein cholesterol (LDL-C) and high density lipoprotein
      cholesterol (HDL-C) were compared before and after treatment between the two
      groups. The relationship of the efficacy was analyzed in terms of the syndrome
      differentiation, age, duration of sickness, obesity and hereditary factors.
      RESULTS: After the treatment, the levels of FPG, FINS, Homa-IR, TC, TG and LDL-C
      were reduced obviously (all P < 0.01) and the levels of ISI, Homa-beta and HDL-C
      were increased apparently (all P < 0.01). The total clinical effective rate was
      80.7% (67/83), in which, that of kidney yin deficiency syndrome was 83.7% (41/49)
      and that of yin and yang deficiency syndrome was 76.5% (26/34). The efficacy was
      not different significantly between the two syndromes. But, the younger the age
      was, the better the efficacy was. CONCLUSION: Acupuncture positively regulates
      the glucose and lipid metabolism in the patients of T2DM. This therapy improves
      insulin resistance, enhances the body sensitivity to insulin and improves insulin
      beta-cell function. The efficacy is related to the patient's age.

PMID- 24673049
TI  - [Brief talk on painless blood-letting therapy at Jing-well points with three
      edged needle].

PMID- 24673048
TI  - [Clinical research on warm acupuncture therapy for pain in postmenopausal
      osteoporosis].
AB  - OBJECTIVE: To observe the clinical efficacy on pain in postmenopausal
      osteoporosis treated with the warm acupuncture therapy and discuss its effect
      mechanism. METHODS: Ninety cases of postmenopausal osteoporosis were randomized
      into a warm acupuncture group, an electroacupuncture group and a medication
      group, 30 cases in each group. In the warm acupuncture group and the
      electroacupuncture group, Dazhu (BL 11), Shenshu (BL 23) and Xuanzhong (GB 39)
      were selected bilaterally and stimulated with the warm acupuncture and
      electroacupuncture therapies respectively, once a day for 30 days totally. In the
      medication group, caltrate-D tablets were prescribed, 600 mg, once a day for 30
      days totally. The changes in the bone density T value, visual analogue scale
      (VAS) score, serum insulin like growth factor 1 (IGF-1), interleukin 6 (IL-6) and
      tumor necrosis factor (TNF-alpha) were observed before and after treatment in the
      three groups. RESULTS: (1) The bone density T value in the patients of
      postmenopausal osteoporosis did not change obviously after 30 days treatment with
      the three therapies; (2) VAS score was all reduced after treatment, in which, the
      result in the warm acupuncture group was the most obvious (6.73 +/- 0.24 before
      treatment vs 4.43 +/- 0.26 after treatment). The value after treatment in the
      warm acupuncture group was different significantly as compared with the
      electroacupuncture group (5.13 +/- 0.31) and the medication group (5.17 +/- 0.33,
      both P < 0.05). (3) The level of serum IGF-1 was improved after treatment in the
      warm acupuncture therapy [(119.5 +/- 20.1) ng/mL before treatment vs (156.5 +/-
      23.9) ng/mL after treatment], which was more apparent as compared with the
      electroacupuncture group [(136.3 +/- 24.5) ng/mL] and the medication group
      [(127.7 +/- 22.1) ng/mL, all P < 0.05]. Concerning to reducing the levels of IL-6
      and TNF-alpha in serum, the results in the warm acupuncture group were superior
      to the other two groups (all P < 0.05). CONCLUSION: The warm acupuncture therapy
      achieves the significant efficacy on pain in postmenopausal osteoporosis, which
      could be related to increasing the level of IGF-1, decreasing the levels of IL-6
      and TNF-alpha, promoting bone formation and inhibting bone absorption.

PMID- 24673050
TI  - [Premature ovarian failure treated with acupoint catgut implantation and
      artificial periodic therapy: a randomized controlled trial].
AB  - OBJECTIVE: To compare the difference in the clinical efficacy on premature
      ovarian failure (POF) between the acupoint catgut implantation combined with
      artifical periodic therapy and the simple artificial periodic therapy and explore
      its effect mechanism. METHODS: Sixty-five patients of POF were randomized into
      the two groups. In a western medication group, 32 cases were treated with the
      artificial periodic therapy with the oral administration of medroxyprogesterone
      acetate tablets. In a catgut implantation + western medication group, 33 cases
      were treated with the acupoint catgut implantation combined with artificial
      periodic therapy. The acupoints of Neiguan (PC 6), Zusanli (ST 36), Guanyuan (CV
      4) and Sanyinjiao (SP 6) were selected. The treatment was lasted for half a year
      and the follow-up visit was for another half a year in the two groups. Kupperman
      index was used to assess the improvements in the clinical symptoms. The levels of
      serum sexual hormones such as follicle stimulating hormone (FSH) and estradiol
      (E2) were evaluated of the patients in the two groups before and after treatment.
      The efficacy was compared between the two groups. RESULTS: The scores of the
      clinical symptoms were all significantly improved after treatment and in the
      follow-up in the two groups (P < 0.01, P < 0.05). In the 6-month follow-up visit
      after treatment, the result in the catgut implantation + western medication group
      was better than that in the western medication group (8.17 +/- 1.19 vs 13.68 +/-
      1.08, P < 0.01). FSH was reduced after treatment in the two groups (all P < 0.01)
      and E2 was increased (all P < 0.05). The curative and remarkably effective rates
      were 75.8% (25/33) and 81.8% (27/22) after treatment and in the follow-up visit
      in the catgut implantation + western medication group, which were better than
      67.9% (19/28) and 53.6% (15/28) in the western medication group separately (P <
      0.05, P < 0.01). CONCLUSION: The acupoint catgut implantation combined with
      artificial periodic therapy achieve the remarkable improvements in the clinical
      symptoms of POF in the patients and the better results as compared with the
      simple western medication therapy. The combined therapys efficacy is stable and
      the long-term efficacy is apparently superior. The effect mechanism is related to
      the improvements in the serum sexual hormone levels.

PMID- 24673051
TI  - [Clinical research on acupoint catgut implantation in the prevention and
      treatment of postpartum pain of uterine contraction with qi and blood
      deficiency].
AB  - OBJECTIVE: To observe the impacts of the acupoint catgut implantation on
      postpartum pain of uterine contraction with qi and blood deficiency. METHODS: One
      hundred and ten primiparas of natural delivery differentiated as qi and blood
      deficiency pattern in TCM were selected as the subjects. They were randomized
      into an acupoint catgut implantation group (55 cases) and a routine nursing group
      (55 cases). In the acupoint catgut implantation group, the catgut was implanted
      in Zigong (EX-CA 1), Zusanli (ST 36), Sanyinjiao (SP 6), Pishu (BL 20) and Geshu
      (BL 17) in 6 h after delivery; additionally, the routine post-delivery nursing
      was adopted. In the routine nursing group, the routine post-delivery nursing was
      applied simply. Visual analogue scale (VAS) and the pain relief time of uterine
      contraction were compared in 24 h, 48 h, 72 h and 96 h after acupoint catgut
      implantation between the two groups. RESULTS: VAS Scores in 24 h, 48 h, 72 h and
      96 h after acupoint catgut implantation in the acupoint catgut implantation group
      were lower apparently than those in the routine nursing group (3.31 +/- 0.39 vs
      4.31 +/- 0.29, 1.86 +/- 0.29 vs 2.66 +/- 0.25, 0.89 +/- 0.21 vs 1.59 +/- 0.24,
      0.35 +/- 0.10 vs 0.69 +/- 0.13, all P < 0.05). The pain relief was achieved in
      (72.06 +/- 6.83) h in the acupoint catgut implantation group and was (123.42 +/-
      11.12) h in the routine nursing group. The pain relief in the acupoint catgut
      implantation group was achieved more quickly (P < 0.01). CONCLUSION: The
      intervention of acupoint catgut implantation in 6 h after natural delivery in
      primiparas prevents effectively postpartum pain of uterine contraction.

PMID- 24673052
TI  - [Efficacy observation of acupuncture method of tonifying-qi and dredging-meridian
      for blepharospasm].
AB  - OBJECTIVE: To compare differences of therapeutic effect between acupuncture
      method of tonifying-qi and dredging-meridian and conventional acupuncture method.
      METHODS: Seventy cases of blepharospasm were randomly divided into an observation
      group and a control group, 35 cases in each one. Cuanzhu (BL 2), Yuwei (Extra)
      through Yuyao (EX-HN 4), Xinming 1 (Extra), Sibai (ST 2) and Yintang (GV 29) were
      selected as main acupoints. The acupuncture method of tonifying-qi and dredging
      meridian was applied in the observation group, which was an acupuncture
      manipulation that could achieve strong needling sensation of qi arrival combined
      with electric-impulse stimulation. The conventional acupuncture method was
      applied in the control group. The treatment was given once every other day, 10
      times as a session for continuous three sessions in both groups. The severity of
      blepharospasm was compared before and after treatment in two groups and clinical
      therapeutic effect was assessed. Follow-up visit was performed after half a year
      to observe the recurrence rate. RESULTS: The cured and markedly effective rate
      was 77.1% (27/35) in the observation group, which was superior to 51.4% (18/35)
      in the control group (P < 0.05). Among cured and markedly effective patients in
      both groups, the recurrence rate was 20.0% (4/20) in the observation group, which
      was inferior to 54.5% (6/11) in the control group (P < 0.05) in the follow-up
      visit. CONCLUSION: The acupuncture method of tonifying-qi and dredging-meridian
      could effectively improve severity of blepharospasm, which has superior short
      term and long-term effects to conventional acupuncture method.

PMID- 24673053
TI  - [Case of sublingual cavernous hemangioma].

PMID- 24673054
TI  - [Efficacy observation on acupuncture combined with bloodletting for chronic
      urticarial].
AB  - OBJECTIVE: To observe differences of therapeutic effect between acupuncture
      combined with bloodletting and regular western medication on chronic urticarial.
      METHODS: One hundred and sixty patients were randomly divided into an acupuncture
      bloodletting group and a loratadine group, 80 cases in each group. In the
      acupuncture bloodletting group, Quchi (LI 11), Neiguan (PC 6), Xuehai (SP 10) and
      Sanyinjiao (SP 6) were selected and manipulated with reducing method, and
      pricking bloodletting with three-edge needle and cupping were given at Feishu (BL
      13) and Geshu (BL 17), once every other day. The oral administration of 10 mg
      loratadine was applied in the loratadine group, once a day. The therapeutic
      effect in two groups was observed and compared after four weeks. RESULTS: The
      cured and markedly effective rate was 91.3% (73/80) in the acupuncture
      bloodletting group, which was similar to 81.3% (65/80) in the loratadine group (P
      > 0.05). The scores of symptom-sign in the two groups were reduced after
      treatment (10.14 +/- 1.95 vs 2.12 +/- 40.32, 10.30 +/- 1.82 vs 3.21 +/- 0.28,
      both P < 0.01), but there was no statistically significant difference between two
      groups after treatment (P > 0.05). There was no obvious adverse effect in the
      acupuncture bloodletting group while 3 cases of mild somnolence were reported in
      the loratadine group. CONCLUSION: The acupuncture bloodletting is an effective
      method for chronic urticarial, which has similar effect to loratadine without
      adverse effect.

PMID- 24673055
TI  - [Case of Meige syndrome].

PMID- 24673056
TI  - [Clinical efficacy observation of heat-sensitive moxibustion with different doses
      for irritable bowel syndrome].
AB  - OBJECTIVE: To compare differences of clinical therapeutic effect of heat
      sensitive moxibustion with different doses for irritable bowel syndrome (IBS).
      METHODS: Sixty cases of IBS were randomly divided into a saturated-dose group (30
      cases) and a traditional-dose group (30 cases). Heat-sensitive moxibustion was
      applied in both groups. The acupoints that had the strongest heat-sensitive
      feeling were selected and treated by warm and suspended moxibustion with moxa
      stick. Disappearance of heat-sensitive feeling was taken as the sign of treatment
      time in the saturated-dose group, while the traditional-dose group was treated
      for 15 min each time. The treatment in both groups was given twice a day for
      first 5 days, and from the sixth day it was given once a day for continuous 25
      times, totally 30 days. Clinical symptom scores and therapeutic effect before and
      after treatment in two groups were observed. RESULTS: After the treatment, the
      cured and markedly effective rate was 75.0% (21/28) in the saturated-dose group,
      which was inferior to 44.4% (12/27) in the traditional-dose group (P < 0.05). The
      clinical symptom scores, including diarrhea, abdominal distension and pain, were
      obviously reduced in two groups compared with those before the treatment (all P <
      0.05). Compared with the traditional-dose group, the symptom scores of diarrhea
      and abdominal distension in the saturated-dose group were obviously decreased
      (0.87 +/- 0.13 vs 1.27 +/- 0.21, P < 0.01; 1.12 +/- 0.41 vs 1.32 +/- 0.26, P <
      0.05). CONCLUSION: The moxibustion featured with disappearance of heat-sensitive
      feeling and saturated dose has better therapeutic effect than that with
      traditional-dose for treatment of IBS. As individual dynamic amount of
      moxibustion, disappearance of heat-sensitive and quantitation varies from person
      to person, which is one of the key factors to obtain the best curative effect.

PMID- 24673057
TI  - [Discussion on twirling reinforcing-reducing method].
AB  - The essence of twirling reinforcing-reducing method is discussed to provide
      theoretical guidance for clinical application of reinforcing-reducing method.
      Through retrospection on historical literature of twirling reinforcing-reducing
      method, records and explanatory notes are thoroughly explored. Several existing
      opinions are analyzed and explained for instance twirling method has connection
      with circulation direction of channels; twirling method is subdivided into right
      and left, male and female, hand and foot; twriling method is related to quantity
      of stimulus and operation time; twriling method belongs to spiral motion and so
      on. As a result, it is found that the key of twirling reinforcing-reducing method
      is the posture of needle-holding hand that defines three-dimensional motion. If
      twirling method is subdivided into right and left, male and female, hand and foot
      and so on, steric effects of lifting-thrusting movement that come along with
      twirling method could be ignored at the same time. It is that the essence of
      twirling reinforcing-reducing method is close to the principle of lifting
      thrusting reinforcing-reducing method, enriching effect with slow insertion and
      fast withdrawal of needle while reducing effect with fast insertion and slow
      withdrawal, which is recorded in Miraculous Pivot: Nine needle and Twelve Yuan.
      With this principle as guide, manipulation could be avoided to become a mere
      formality and illusory metaphysics during clinical application of twirling
      reinforcing-reducing method.

PMID- 24673058
TI  - [Forty-nine cases of Parkinson's disease treated by acupuncture adjunctive
      therapy].

PMID- 24673060
TI  - [Case of neuromyelitis optica].

PMID- 24673059
TI  - [Effects of warm moxibustion on CD40-CD40L axis in rabbits with atherosclerosis].
AB  - OBJECTIVE: To explore effects and action mechanism of warm moxibustion on
      regulation of blood lipids and anti-atherosclerosis. METHODS: Forty-one male
      Japanese big-ear white rabbits were randomly divided into a blank group (10
      rabbits), a model group (10 rabbits), a moxibustion group (10 rabbits) and a
      medication group (11 rabbits). Normal diet was applied in the blank group while
      high-cholesterol diet combined with injection of bovine serum albumin were
      applied in the rest groups to establish rabbit model of atherosclerosis. After
      establishment, the model group was not intervened and warm moxibustion was
      applied in the moxibustion group at "Zusan-li" (ST 36) and "Shenque" (CV 8), 10
      min per acupoint per day for continuous 4 weeks. The medication group was treated
      with intragastric administration of lovastatin capsule (3.6 mg/kg) for continuous
      4 weeks. The level of blood lipids, such as total cholesterol (TC), triglyceride
      (TG), and content of CD40 ligand (CD40L), soluble CD40 ligand (sCD40L) and
      expression of nuclear factor NF-kappaB were tested after 4 weeks. RESULTS:
      Compared with the model group, the moxibustion group and medication group could
      effectively reduce the contents of TC and low density lipoprotein (all P < 0.05),
      lower the level of sCD40L [(8.310 +/- 1.221) ng/mL in the model group, (7.097 +/-
      0.846) ng/mL in the moxibustion group and (7.354 +/- 0.631) ng/mL in the
      medication group], reduce expression of CD40L [(0.235 +/- 0.179) mm2 in the model
      group, (0.072 +/- 0.079) mm2 in the moxibustion group and (0.039 +/- 0.015) mm2
      in the medication group] and NF-kappaB [(0.145 +/- 0.052)mm2 in the model group,
      (0.052 +/- 0.012) mm2 in the moxibustion group and (0.036 +/- 0.013) mm2 in the
      medication group], indicating the significant difference (P < 0.05, P < 0.001).
      There was no statistical difference between the moxibustion group and medication
      group (all P > 0.05). CONCLUSION: The warm moxibustion has great effect on
      regulation of blood lipids and anti-atherosclerosis, in which lowering expression
      of CD40-CD40L could be one of possible mechanisms to take effect of anti
      atherosclerosis.

PMID- 24673061
TI  - [Effects of moxibustion on concentration of extracellular potassium ion in
      acupoint under different status].
AB  - OBJECTIVE: To observe different effects of moxibustion on extracellular potassium
      ion in acupoint under physiological and pathological status and provide
      experimental evidence for exploring action mechanism of moxibustion on acupoint
      local. METHODS: Forty female SD rats were randomly divided into a blank group, a
      blank-moxibustion group, a model group and a model-moxibustion group, 10 cases in
      each one. The complete Freund's adjuvant(CFA) was adopted to establish model of
      adjuvant arthritis (AA) in the model group and model-moxibustion group. No
      treatment was given in the blank group and model group while moxibustion was
      applied at "Zusan-li" (ST 36) for 30 min in the blank-moxibustion group and model
      moxibustion group. The tissue fluid in "Zusanli" (ST 36) was collected with
      microdialysis and real-time analyzed by electrolytic analyzer. The change of
      concentration of potassium ion in "Zusanli" (ST 36) was observed. RESULTS: (1)
      Under physiological status, the concentration of extracellular potassium ion in
      the blank group was not changed within 150 min (P > 0.05); before the
      moxibustion, the concentration of extracellular potassium ion in the blank
      moxibustion group was (1.21 +/- 0.31) mmol/L, and after treatment it was
      gradually increased and reached its peak at (2.38 +/- 0.42) mmol/L after 60 min
      (P < 0.05), then it was reduced. 150 min after the treatment, concentration of
      potassium ion was slightly higher than that before moxibustion as well as that in
      the blank group. The concentration in the blank-moxibustion group at 60 min was
      statistically significant compared with that in the blank group (P < 0.05). (2)
      Under pathological status, the concentration of extracellular potassium ion in
      the model group was not changed within 150 min, differences of which at each time
      point was not statistically significant (all P > 0.05). Before the moxibustion,
      the concentration of extracellular potassium ion was (1.09 +/- 0.12) mmol/L in
      the model-moxibustion group, and it was immediately increased to (1.96 +/- 0.18)
      mmol/L after moxibustion. 60 min and 90 min after the moxibustion, it still
      maintained a higher level, which was (1.87 +/- 0.29) mmol/L and (1.59 +/- 0.16)
      mmol/L respectively (both P < 0.05). The differences of each time point after
      moxibustion in the model-moxibustion group were statistically significant
      compared with those in the model group (all P < 0.05). CONCLUSION: The
      moxibustion could increase the concentration of potassium ion in rat's acupoint
      local under physiological status but time of effect is short; with moxibustion at
      "Zusanli" (ST 36) under pathological status, the concentration of local potassium
      ion is obviously increased and maintains for a long time.

PMID- 24673063
TI  - [Moving cupping at three yang meridians of hand for cervical spondylosis].

PMID- 24673062
TI  - [Nanometer wave combined with acupuncture for 30 cases of postoperative abdominal
      incision liquefaction].

PMID- 24673064
TI  - [Clinical observation on fuzhong (supporting the middle-jiao) manipulation of
      tuina for infantile anorexia].
AB  - OBJECTIVE: To observe clinical therapeutic effect of fuzhong (supporting the
      middle-jiao) manipulation of tuina for infantile anorexia. METHODS: Eighty-one
      children with anorexia were treated with fuzhong manipulation, including
      abdominal kneading, acupressure at Zhongwan (CV 12), Lanmen (Extra), Tianshu (ST
      25), Zusanli (ST 36), Sanyinjiao (SP 6), spine pinching, warm moxibustion and
      warm scraping with supporting-yang cupping, three times a week, six times as a
      session. Onset time, therapeutic effect and TCM symptom scores before and after
      treatment were observed after two sessions and differences of therapeutic effect
      among different patterns were compared. RESULTS: Seventy-two children had the
      effect in one session while 41 children had the effect within half of a session.
      38 cases were clinically cured, 15 cases were markedly effective, 23 cases were
      effective and 5 cases were failed. The total effective rate was 93.8%. Compared
      with before treatment, TCM symptom scores, including appetite, food intake,
      complexion and defecation, were all obviously improved after treatment (all P <
      0.001). The clinical cured rate was 45.2% (19/42) in the pattern of dysfunction
      of spleen in transportation, 45.8% (11/24) in the pattern of qi deficiency of
      spleen and stomach, 50.0% (4/8) in the pattern of yin deficiency of spleen and
      stomach, 57.1% (4/7) in the pattern of liver sufficiency and spleen
      insufficiency, which had no obvious differences among different patterns (all P >
      0.05). CONCLUSION: The fuzhong manipulation of tuina has quick onset time and
      satisfied clinical therapeutic effect, which could obviously improve symptoms and
      is fit for different patterns of infantile anorexia.

PMID- 24673065
TI  - [Acupucture at Dong's extra acupoint combined with exercise for 61 cases of acute
      chest].

PMID- 24673066
TI  - [Needling technique of Professor Li Yan-Fang].
AB  - Experiences of needling techniques of Professor LI Ya- fang is introduced in this
      article. Gentle and superficial insertion is adopted by Professor LI in clinic.
      Emphases are put on the qi regulation function, needling sensation to the
      affected region and insertion with both hands, especially the function of the
      left hand as pressing hand. The gentle and superficial insertion should be done
      as the follows: hold the needle with the right hand, press gently along the
      running course of meridians with the left hand to promote qi circulation, hard
      pressing should be applied at acupoints to disperse the local qi and blood,
      insert the needle gently and quickly into the subcutaneous region with the right
      hand, and stop the insertion when patient has the needling sensation. While the
      fast needling is characterized with shallow insertion and swift manipulation: the
      left hand of the manipulator should press first along the running course of the
      meridian, and fix the local skin, hold the needle with the right hand and insert
      the needle quickly into the acupoint. Withdrawal of the needle should be done
      immediately after the reinforcing and reducing manipulations. Professor LI is
      accomplished in qi regulation. It is held by him that regulating qi circulation
      is essence of acupuncture, letting the patient get the needling sensation is the
      most important task of needling. Lifting, thrusting and rotation manipulations
      should be applied to do reinforcing or reducing. The tissue around the tip of the
      needle should not be too contracted or too relaxed, and the resistance should not
      be too strong or too weak. The feeling of the insertion hand of the practitioner
      should not be too smooth or too hesitant. Needle should be inserted into the skin
      quickly at the moment of hard pressing by the left hand. And then, slow rotation
      and gentle lifting and thrusting can be applied to promote the needling sensation
      like electric current pass through and to reach the affected region along the
      running course of meridians.

PMID- 24673067
TI  - [Treatment of otorhinolaryngologic diseases of deficient heat type with Professor
      XIE Qiang's Tihu Guanding needling method].
AB  - Professor XIE Qiang's Tihu Guanding needling method, a kind of acupuncture method
      which takes acupoints of the Conception Vessel as the primary and acupoints of
      the Governor Vessel as the secondary. Acupoints Lianquan (CV 23), Tiantu (CV 22),
      Qihai (CV 6), Zhongwan (CV 12), Baihui (GV 20) and Dazhui (GV 14) are adopted as
      the basic ones. Other points can be added according to various symptoms, for
      instance, Yingxiang (LI 20) and Yintang (GV 29) for rhinopathy, Tinggong (SI 19)
      and Yifeng (TE 17) for otopathy, Yan'an (Professor XIE's experience) and
      Shanglianquan (EX-HN 21) for pharyngopathy and Kaiyin 1 (Professor XIE's
      experience) and Kaiyin 2 (Professor XIE's experience) for laryngopathy. During
      the needle retention, rotation manipulation should be done every 5 min at
      Lianquan (CV 23). And the patient should be told to put the tip of one's tongue
      at the the palate as well as to do deep breathing to communicate the Conception
      Vessel and the Governor Vessel. Moxibustion is adopted at Yongquan (KI 1) to
      induce the up floating fire to mingmen (where the primary yang is stored). The
      therapeutic effect on treatment of persistent otorhinolaryngologic diseases with
      the above mentioned method is approve to be good.

PMID- 24673068
TI  - [Contribution of Professor SHI Xue-min's academic thoughts to treatment of
      stroke].
AB  - Based on the thought of Zhishen (a kind of mind regulation), Professor SHI Xue
      min, academician of the China Academy of Engineering, found the Xingnao Kaiqiao
      (to refresh the mind and to cause resuscitation) acupuncture method, which still
      plays an important role in the acupuncture treatment of wind stroke nowadays.
      Meanwhile, great importance is attached to the comprehensive treatment of wind
      stroke. Danqi Piantan capsule (see text) is developed and "wind stroke unit" is
      set up. In recent years, Professor SHI shifts the center of research to the
      treatment of hypertension, the risk factor of wind stroke. Taking Renying (ST 9)
      as the major acupoint, acupuncture with standard measurement and manipulations is
      established. And good clinical effect has been obtained as well. Therefore, this
      article focuses on the introduction of Professor SHI Xue-min's contribution to
      wind stroke treatment.

PMID- 24673069
TI  - [Thinking on designation of sham acupuncture in clinical research].
AB  - Randomized controlled trials (RCT) is the source of the raw data of evidence
      based medicine. Blind method is adopted in most of the high-quality RCT. Sham
      acupuncture is the main form of blinded in acupuncture clinical trial. In order
      to improve the quality of acupuncture clinical trail, based on the necessity of
      sham acupuncture in clinical research, the current situation as well as the
      existing problems of sham acupuncture, suggestions were put forward from the
      aspects of new way and new designation method which can be adopted as reference,
      and factors which have to be considered during the process of implementing.
      Various subjective and objective factors involving in the process of trial should
      be considered, and used of the current international standards, try to be
      quantification, and carry out strict quality monitoring.

PMID- 24673070
TI  - [Question on location of Baihui (GV 20)].

PMID- 24673071
TI  - [Acupuncture for 58 cases of central pain after spinal cord injury].

PMID- 24673072
TI  - [Differentiation and analysis on YAN Ming-guang and XU Feng's Najia fa (day
      prescription of acupoints)].
AB  - The traditional Najiafa (day-prescription of acupoints) can be classified into
      two schools of YAN Ming-guang and XU Feng. The author studied the YAN Ming-guang
      and XU Feng Najia fa from the aspects of the academic source, selection of
      points, existing researches and current application. When compared between the
      two schools, it is held that Najia fa of YAN Ming-guang school more accords with
      the law of point selection according to Ziwu Liuzhu Zhenfa (acupuncture based on
      the midnight-noon and ebb-flow doctrine) in following the original doctrine,
      selection of points on the base of day-prescription, and time-meridian relation
      of Sanjiao (triple energizer) and Pericardium meridians. Therefore, it is
      concluded that the YAN's Najia fa should not be neglected and forgotten. Its
      inheritage and further study should be carried out so as to enrich the ways of
      study as well as the prevention and treating methods in clinic.

PMID- 24673073
TI  - [Urticaria treated by plum blossom needle].

PMID- 24673074
TI  - [Acupoint catgut-embedding for 35 cases of insomnia].

PMID- 24673075
TI  - [Research and practice on basic skill training and technique improving of
      acupuncture and tuina major].
AB  - In order to summarize and perfect the basic skill practicing method in
      acupuncture teaching and form a characteristic teaching, the research on skill
      training and technique improving of acupuncture and tuina major was carried out.
      The undergraduate students in acupuncture and tuina major from College of
      Acupuncture-Moxibustion and Tuina were randomly divided into an experimental
      group and a control group. Students from both groups received the basic courses
      of acupuncture-moxibustion and tuina as requested in the syllabus and the special
      teaching was added to the experimental group, namely "three practice" (strength
      practice, coordination practice, targeted practice of acupuncture basic skills)
      and "three enlightenment" (technique enlightenment, mind and qi enlightenment,
      efficacy enlightenment). During and after the courses, the teaching effectiveness
      was evaluated on the basis of needling manipulation. The peacetime score in the
      experimental group was superior to that in the control group (38.03 +/- 1.14 vs
      33.25 +/- 1.31, P < 0.05), the total score in the experimental group was superior
      to that in the control group (84.03 +/- 6.30 vs 78.05 +/- 6.55, P < 0.05). The
      special teaching method of "three practice" and "three enlightenment" can improve
      the effect of skill training teaching method. It highlights the unique feature of
      central plains by integrating the essence of Shaolin internal qigong and Chen
      style Taiji, it can also provide new ideas for the practical teaching of TCM
      professional courses and the construction of characteristic professionals.

PMID- 24673076
TI  - [Encephalopathy therapeutic tongue acupoint apparatus (ETTAA) for 42 cases of
      autism].
AB  - OBJECTIVE: To observe the efficacy of encephalopathy therapeutic tongue acupoint
      apparatus (ETTAA) in the treatment of autism. METHODS: Eighty-four children of
      autism were randomly divided into a tongue acupuncture group (group A) and a
      conventional training group (group B), 42 cases in each group. The behavior
      training and sensory integration training were carried out in group B and the
      ETTAA was added in group A. The apparatus was switched on for 20 min every time
      and 3 times a day. Treatment of two months were carried out in both groups. The
      score of childhood autism rating scale (CARS) and clinical efficacy in both
      groups were observed before and after treatment. RESULTS: After treatment, the
      CARS in both groups were significantly reduced (42.39 +/- 6.86 vs 32.15 +/- 5.12,
      P < 0.001; 44.58 +/- 6.76 vs 39.72 +/- 7.11, P < 0.05), which was more
      significant in group A (P < 0.01). The totally effective rate in group A [90.5%
      (38/42)] was superior to that in group B [66.7% (28/42), P < 0.01]. CONCLUSION:
      The clinical efficacy in tongue acupuncture group is apparently superior to that
      in conventional training group, ETTAA combined with conventional training have a
      better curative effect in the treatment of autism.

PMID- 24673077
TI  - [Application and research of acupuncture in military].
AB  - Acupuncture has remarkable effects of pain relieving and functional restoration
      on injuries of soft tissue and joint due to military training. As more and more
      attention has been attached to the impact of psychological states and biorhythm
      disorder on the fighting ability of military staff, acupuncture has found its
      place in treating chronic fatigue, combat stress reaction, traumatic brain injury
      and post-traumatic stress disorder as well as regulating circadian rhythms. The
      therapeutic effect of acupuncture in military training-related physical damage
      and psychological trauma has already been proved by numerous clinical practices
      and researches. It is held that using acupuncture as an alternative could not
      only save medical resources, but also enhance the fighting ability of the army.
      However, the current clinical studies is facing the problem of limited sample
      size. Therefore, randomized controlled trials in large scale and multiple centers
      should be further carried out toward military staff, so as to provide more
      speaking evidences to the prevention and treatment of physical and psychological
      diseases.

PMID- 24673078
TI  - An ancient scourge triggers a modern emergency.

PMID- 24673079
TI  - Arabic version of the Global Mental Health Assessment Tool-Primary Care version
      (GMHAT/PC): a validity and feasibility study.
AB  - Mental health services are far from satisfactory in the Eastern Mediterranean
      Region. The Global Mental Health Assessment Tool-Primary Care version (GMHAT/PC)
      is a semi-structured, computerized clinical assessment tool that was developed to
      assist health workers in making quick, convenient and comprehensive standardized
      mental health assessments. A study was carried out in the United Arab Emirates to
      evaluate the validity and feasibility of the Arabic version of the GMHAT/PC.
      Mental health nurses administered the GMHAT/PC Arabic version to 50 patients in
      mental health and rehabilitation settings and their GMHAT/PC diagnosis was
      compared with the psychiatrist's independent ICD-10 based clinical diagnosis on
      the same patients. The nurses found GMHAT/PC easy to administer in an average of
      16 minutes. The GMHAT/PC-based diagnosis had a good agreement with the
      psychiatrist's diagnosis (kappa = 0.91) and a high sensitivity (97%) and
      specificity (94%).

PMID- 24673080
TI  - Predictors of smoking among male college students in Saudi Arabia.
AB  - Identifying the predictors of smoking in one of the top cigarette-consuming
      countries in the world is a vital step in smoking prevention. A cross-sectional
      study assessed the predictors of smoking in a cohort of male students in 3
      universities in Saudi Arabia. A pre-tested, validated questionnaire was used to
      determine sociodemographic characteristics, academic performance, peers' smoking,
      and presence of a smoker within the family. Of the 337 participants, 30.9% were
      current smokers (smoked 1 or more cigarettes within the last 30 days). Lower
      academic performance (OR = 2.29, 95% CI: 1.02-5.17), peer smoking (OR = 4.14, 95%
      CI: 1.53-11.3) and presence of other smokers in the family (OR = 2.77, 95% CI:
      1.37-5.64) were the significant predictors of smoking status identified using
      multiple logistic regression analysis. These findings highlight the influence of
      family and peer pressure in initiating cigarette use among the youth of Saudi
      Arabia.

PMID- 24673081
TI  - Salt intake in Eastern Saudi Arabia.
AB  - High salt intake has been associated with adverse side-effects such as
      hypertension and cardiovascular disease. The amount of salt intake among the
      population of Saudi Arabia is not known. The objective of this study was to
      estimate the salt intake among residents of the Eastern region of Saudi Arabia by
      measuring 24-hour urinary sodium excretion. Urine samples were collected from 130
      individuals aged over 14 years for measurement of levels of sodium and other
      electrolytes. A total of 87 samples met the criteria for accuracy and were
      analysed. Total mean 24-hour sodium excretion for the group was 140 (SD 49) mEq
      [153 (SD 52) mEq for males and 118 (SD 37) mEq for females]. These values exceed
      the recommended daily intake of sodium and may contribute to the risk of
      developing hypertension and cardiovascular disease in Saudi Arabia.

PMID- 24673082
TI  - Investigating inspection practices of pharmaceutical manufacturing facilities in
      selected Arab countries: views of inspectors and pharmaceutical industry
      employees.
AB  - There are few studies that explore inspection practices of pharmaceutical
      facilities from the viewpoint of inspectors and industry employees. In this
      descriptive, cross-sectional study, inspectors and quality assurance staff from 4
      Arab countries--the United Arab Emirates, Saudi Arabia, Egypt and Jordan--were
      surveyed about their inspection practices and views. There was considerable
      variation in inspection practices across countries and between the inspectorate
      and quality assurance staff within countries. Divergence was found in views
      associated with payment mechanisms. There was mutual agreement by both groups
      that inspectors were in short supply and that they needed to be better trained.
      Inspectors appeared to have less authority than expected in order to control
      pharmaceutical manufacturing and marketing activities. Compounding this was a
      dearth of policy which would support a more uniform and systematic approach to
      the inspection process within and across countries.

PMID- 24673083
TI  - Pharmacovigilance in Qatar: a survey of pharmacists.
AB  - Active national pharmacovigilance programmes are needed to monitor adverse drug
      reaction (ADR) data in local populations. The objective of this study was to
      describe the knowledge, experiences, attitudes and perceived barriers to
      reporting of suspected ADRs by pharmacists in Qatar. A 27-item web-based survey
      was answered by 116 pharmacists (25% response rate). Knowledge of ADR terminology
      and reporting purpose was high, but only 29.3% had ever made a suspected ADR
      report in Qatar. Most respondents expressed positive attitudes towards the
      pharmacist's role in pharmacovigilance. Inability to recognize a potential ADR or
      access a reporting form were perceived as barriers. Enhanced training and
      efficiency in report submissions were identified as facilitators to future
      participation. Hospital pharmacists were 7 times more likely to have reported a
      suspected ADR in Qatar. Pharmacists in Qatar are willing to engage in
      pharmacovigilance activities if supported by increased training and transparency
      in the reporting process.

PMID- 24673084
TI  - Isolation and identification of Legionella pneumophila from drinking water in
      Basra governorate, Iraq.
AB  - This study in Iraq investigated the occurrence of Legionella. pneumophila in
      different drinking-water sources in Basra governorate as well as the
      susceptibility of isolates to several antibiotics. A total of 222 water samples
      were collected in 2008-2009: 49 samples from water purification plants (at entry
      points, from precipitation tanks, from filtration tanks and at exit points), 127
      samples of tap water; and 46 samples from tankers and plants supplying water by
      reverse osmosis. The findings confirmed the presence of L. pneumophila in sources
      of crude water, in general drinking water supplies and drinking water tankers. Of
      258 isolates 77.1% were serotype 1 and 22.9% serotypes 2-15. All examined
      isolates displayed drug resistance, particularly to ampicillin, but were 100%
      susceptible to doxycycline. The prevalence of L. pneumophila, especially
      serogroup 1, is a strong indicator of unsuitability of drinking water and
      requires appropriate action.

PMID- 24673085
TI  - Molecular typing of Mycobacterium spp. isolates from Yemeni tuberculosis
      patients.
AB  - The study was done to characterize at the species level Mycobacterium spp.
      isolates from Yemeni pulmonary tuberculosis patients. Early-morning sputum
      samples were collected from 170 patients referred to the National Tuberculosis
      Institute in Sana'a city with suspected pulmonary tuberculosis. Samples were
      processed with Ziehl-Neelsen stain and cultured in Ogawa and Lowenstein-Jensen
      media. The rpoB gene target sequence was amplified using mutagenesis forward and
      reverse primers followed by Hindlll enzyme digestion. Of the 120 isolates
      analysed, 118 (98.3%) were identified as M. tuberculosis complex and 2 (1.7%)
      were identified as mycobacteria other than M. tuberculosis. The results showed
      that those 2 isolates were multi-drug resistant and the DNA sequencing analysis
      showed that the alignment of nucleic acid of DNA in isolates of mycobacteria
      other than M. tuberculosis was different from that of M. tuberculosis complex.

PMID- 24673086
TI  - High prevalence of Klebsiella pneumoniae carbapenemase-mediated resistance in K.
      pneumoniae isolates from Egypt.
AB  - The emergence and rapid spread of antibiotic-resistant Klebsiella pneumoniae
      isolates harbouring the blaKPC gene that encodes for carbapenemase production
      have complicated the management of patient infections. This study in a tertiary
      care hospital in Egypt used real-time PCR assay to test ertapenem-nonsusceptible
      isolates of K. pneumoniae for the presence of the blaKPC gene and compared the
      results with modified Hodge test. Antibiotic sensitivity was performed by
      standard methods, and interpreted following both the old CLSI breakpoints (M100
      S19) for carbapenems and the revised breakpoints (M100-S22). From the 45 non
      duplicate isolates of K. pneumoniae recovered from different clinical specimens,
      a high prevalence of ertapenem-nonsusceptible isolates (44.4%) was reported using
      the new lower CLSI breakpoints. The blaKPC gene was confirmed in 14/20 (70.0%) of
      these isolates. The high prevalence of ertapenem nonsusceptibility at a tertiary
      care hospital in Egypt was predominantly attributed to K. pneumoniae
      carbapenemase-mediated resistance mechanisms in K. pneumoniae isolates.

PMID- 24673087
TI  - Prognostic factors of Atractylis gummifera L. poisoning, Morocco.
AB  - In Morocco, acute Atractylis gummifera L. poisoning represents the leading cause
      of death by plant poisoning especially for children. All cases received in the
      Moroccan poison control centre from January 1981 to December 2009 (n = 467) were
      included in a retrospective study of the characteristics and risk factors of A.
      gummifera L. poisoning. The most vulnerable age group was children (63.4% of
      cases). Most cases were due to accidental exposure (75.5%), but some were from
      therapeutic use (18.1%) or attempted abortion (7.4%). Patients presented with
      moderate poison severity signs (grade 2) in 22.3% of cases or severe signs (grade
      3) in 21.0%. The mortality rate was 39.2%. The majority of deaths (81.1%)
      occurred in children aged < 15 years following accidental exposure. Multivariate
      logistic regression analysis revealed that risk factors for mortality were coma
      (OR = 20.5); hepatitis (OR = 52.7) and rural residence (OR = 7.26), while gastric
      decontamination was a protector factor (OR = 0.26).

PMID- 24673089
TI  - Mass gatherings.

PMID- 24673088
TI  - Case of acquired lobar emphysema mimicking pneumothorax in a neonate.

PMID- 24673090
TI  - Hajj and the public health significance of mass gatherings.

PMID- 24673091
TI  - Health preparedness and legacy planning at mass gatherings in the EMR: a WHO
      perspective.

PMID- 24673092
TI  - Using health educators to improve knowledge of healthy behaviour among Hajj 1432
      (2011) pilgrims.
AB  - The main objective of this study was to assess the short-term effect on health
      knowledge among pilgrims after being provided specific health education messages.
      A random sample of 6 entry-point buses was selected. A self-administered
      questionnaire was used to assess knowledge before and after intervention; 278
      pilgrims completed the questionnaire. There was a significant increase in the
      proportion of participants who answered all questions correctly after the
      educational intervention (P < 0.05). Almost all respondents stated that they
      benefited from the health education and that the health educator was successful
      in delivering the messages. Only 19 (7.2%) reported that they had already
      received relevant health education messages prior to their arrival in Saudi
      Arabia. Before the intervention just 50% of the respondents knew that safe
      shaving prevents dissemination of bloodborne diseases; this rose to 84.7% after
      the intervention. Direct health education to pilgrims is effective in improving
      short-term health knowledge.

PMID- 24673093
TI  - Pattern of morbidity and mortality in Karbala hospitals during Ashura mass
      gathering at Karbala, Iraq, 2010.
AB  - Religious mass gatherings are increasingly common in Iraq and can harbour
      considerable public health risks. This study was aimed at determining morbidity
      and mortality patterns in hospitals in Karbala city, Iraq during the mass
      gathering for Ashura in 2010. We conducted a cross-sectional study on attendees
      at the 3 public hospitals in the city. The study period was divided into pre
      event, event, and post-event phases. Morbidity and mortality data were obtained
      from hospital registry books and the coroner's office. About 80% of the 18 415
      consultations were at emergency rooms. Average daily emergency room attendance
      was higher during the event compared with pre- and post-event phases, while
      average daily admissions decreased. Compared with the pre-event phase, a 7-fold
      increase in febrile disorders and a 2-fold increase in chronic diseases and
      injuries were noted during the event phase. There was no difference between the 3
      phases for average daily death rate, nor for cause of death.

PMID- 24673094
TI  - Preparedness and health risks associated with Moulay Abdellah Amghar moussem,
      Morocco, 2009-2010.
AB  - The objective of this study was to describe the risks and human health outcomes
      associated with attendance at the Moulay Abdellah Amghar moussem (a pre-planned
      mass gathering attracting more than 360 000 participants) for the purposes of
      public health prevention, planning, preparedness and response. We performed an
      environmental health risk assessment and retrospectively reviewed local health
      centre records before, during and after the event. In addition, standardized
      interviews with key stakeholders were performed to qualitatively evaluate local
      public health preparedness and response capacities. During the event, average
      daily health centre visits increased 5-fold. The sex ratio of health-care visits
      changed significantly from an average of 1.8:1 female:male visits per day to
      1.2:1. The proportion of injuries varied from an average of 3.7% pre- and post
      event to 14.8% (P < 0.01) during the event. A significant increase in digestive
      diseases was also observed during the event. Recommendations include increasing
      accessibility to free sanitation and hygiene facilities and improving health
      communications concerning hand washing and food and water safety.

PMID- 24673095
TI  - Public health surveillance at a mass gathering: urs of Baba Farid, Pakpattan
      district, Punjab, Pakistan, December 2010.
AB  - The objective of this study was to identify health related problems encountered
      during an annual mass gathering in Pakpattan, Pakistan, the anniversary of the
      death (urs) of Baba Farid, and to make recommendations for planning and
      prevention activities. A surveillance system was established to capture health
      related data for the event. A list of reportable diseases was developed. Data
      were collected pre-, during, and post-event by health care workers trained for
      the purpose. A total of 5918 people reported to the 15 health care facilities
      providing services during the event; 58% of consultations were because of
      communicable diseases, 21% of which were respiratory tract infections and 26%
      gastrointestinal illness. Injuries accounted for 31% of cases and noncommunicable
      diseases for 11%. Prevalence of reportable disease during the event showed
      sizeable increases. No major disease outbreak was observed.

PMID- 24673096
TI  - Mass gathering in Aqaba, Jordan, during Eid AI Adha, 2010.
AB  - During the 5-day Eid Al Adha holiday, Aqaba is the site of one of the largest
      mass gatherings in Jordan. Public health concerns during this holiday included:
      food- and waterborne diseases, drowning, injuries by marine creatures, road
      traffic crashes, and pressure on emergency departments at hospitals. This cross
      sectional study was carried out in Aqaba during the period 16-20 November 2010
      and aimed to identify and prioritize the major public health risks and to
      overview the preparedness plans of the Health Directorate during previous Eid
      events in Aqaba. All related stakeholders participated in the study. An
      exploratory visit to Aqaba was made and an introductory workshop was conducted
      for participants. Relevant data were collected and compared with the figures for
      the week prior to the event. No food poisoning outbreaks were reported during the
      event. There was a 23% increase in emergency department attendance, a 33%
      increase in hospital admissions, and road traffic crashes increased by more than
      300%. More males were affected than females.

PMID- 24673097
TI  - Patterns of diseases and preventive measures among domestic hajjis from Central,
      Saudi arabia [complete republication].
AB  - OBJECTIVES: To identify the occurrence of upper respiratory tract infections
      (URTI), diarrheal diseases and trauma during the Haji season, and the practice of
      some preventive measures by pilgrims. METHODS: A cohort study during November and
      December 2009 among hajjis registered while visiting Primary Health Care Centers
      of Riyadh, Kingdom of Saudi Arabia to get mandatory meningococcal meningitis
      vaccination. On return from hajj, hajjis were contacted on telephone to collect
      information on occurrence of URTI and diarrhea along with other associated
      activities in Hajj. RESULTS: Out of 1507 hajjis, 54.7% developed symptoms; 97%
      reported upper respiratory tract symptoms, and 9.3% reported diarrheal symptoms.
      Those < 40 years of age were more likely to develop an URTI. The incidence of
      diarrheal diseases or trauma was not statistically associated with age. No
      statistical difference for educational level was found for U RTI or trauma, but
      there was a statistically significant difference for diarrheal diseases. There
      was no statistical difference for nationality in relation to diarrheal diseases
      and trauma, but there was a statistically significant difference for URTI. There
      was a statistically significant difference of URTI between those pilgrims who
      used the face mask most of the time and those who used it sometimes. CONCLUSION:
      Upper respiratory tract infections is a common health problem among studied
      domestic hajjis. Generally, there is room for improvement in the adoption of
      preventive measures by hajjis; and there is still limited information on the use
      of facemasks in spite of the fact that using it significantly decreases the risk
      for URTI.

PMID- 24673098
TI  - Public health considerations for mass gatherings in the Middle East and North
      Africa (MENA) region.
AB  - This review describes major mass gatherings in the MENA region and the public
      health implications of these events, and provides recommendations for public
      health officials of the host country. Through our search of the literature for
      peer-reviewed publications, we identified relevant 77 papers; all were related to
      the annual Hajj. Using the information obtained from the literature review, the
      Eastern Mediterranean Public Health Network (EMPHNET) and the Centers for Disease
      Control and Prevention (CDC) developed and conducted 2 workshops on Public Health
      Surveillance during Mass Gatherings for field epidemiology training programmes
      and ministry of health focal points from 10 countries. The main potential public
      health concerns associated with mass gatherings include: infectious diseases
      (e.g. respiratory disease, gastro-intestinal tract disease, foodborne disease),
      injuries, traffic accidents, heat-related illnesses, insect stings, non
      communicable diseases and terrorism.

PMID- 24673100
TI  - Nonadiabatic excited-state molecular dynamics: modeling photophysics in organic
      conjugated materials.
AB  - To design functional photoactive materials for a variety of technological
      applications, researchers need to understand their electronic properties in
      detail and have ways to control their photoinduced pathways. When excited by
      photons of light, organic conjugated materials (OCMs) show dynamics that are
      often characterized by large nonadiabatic (NA) couplings between multiple excited
      states through a breakdown of the Born-Oppenheimer (BO) approximation. Following
      photoexcitation, various nonradiative intraband relaxation pathways can lead to a
      number of complex processes. Therefore, computational simulation of nonadiabatic
      molecular dynamics is an indispensable tool for understanding complex
      photoinduced processes such as internal conversion, energy transfer, charge
      separation, and spatial localization of excitons. Over the years, we have
      developed a nonadiabatic excited-state molecular dynamics (NA-ESMD) framework
      that efficiently and accurately describes photoinduced phenomena in extended
      conjugated molecular systems. We use the fewest-switches surface hopping (FSSH)
      algorithm to treat quantum transitions among multiple adiabatic excited state
      potential energy surfaces (PESs). Extended molecular systems often contain
      hundreds of atoms and involve large densities of excited states that participate
      in the photoinduced dynamics. We can achieve an accurate description of the
      multiple excited states using the configuration interaction single (CIS)
      formalism with a semiempirical model Hamiltonian. Analytical techniques allow the
      trajectory to be propagated "on the fly" using the complete set of NA coupling
      terms and remove computational bottlenecks in the evaluation of excited-state
      gradients and NA couplings. Furthermore, the use of state-specific gradients for
      propagation of nuclei on the native excited-state PES eliminates the need for
      simplifications such as the classical path approximation (CPA), which only uses
      ground-state gradients. Thus, the NA-ESMD methodology offers a computationally
      tractable route for simulating hundreds of atoms on ~10 ps time scales where
      multiple coupled excited states are involved. In this Account, we review recent
      developments in the NA-ESMD modeling of photoinduced dynamics in extended
      conjugated molecules involving multiple coupled electronic states. We have
      successfully applied the outlined NA-ESMD framework to study ultrafast
      conformational planarization in polyfluorenes where the rate of torsional
      relaxation can be controlled based on the initial excitation. With the addition
      of the state reassignment algorithm to identify instances of unavoided crossings
      between noninteracting PESs, NA-ESMD can now be used to study systems in which
      these so-called trivial unavoided crossings are expected to predominate. We
      employ this technique to analyze the energy transfer between poly(phenylene
      vinylene) (PPV) segments where conformational fluctuations give rise to numerous
      instances of unavoided crossings leading to multiple pathways and complex energy
      transfer dynamics that cannot be described using a simple Forster model. In
      addition, we have investigated the mechanism of ultrafast unidirectional energy
      transfer in dendrimers composed of poly(phenylene ethynylene) (PPE) chromophores
      and have demonstrated that differential nuclear motion favors downhill energy
      transfer in dendrimers. The use of native excited-state gradients allows us to
      observe this feature.

PMID- 24673099
TI  - Four-step synthesis of the antimalarial cardamom peroxide via an oxygen stitching
      strategy.
AB  - A four-step synthesis of the antimalarial terpene cardamom peroxide, a 1,2
      dioxepane-containing natural product, is reported from (-)-myrtenal and molecular
      oxygen. This highly concise route was guided by biosynthetic logic and enabled by
      an unusual manganese-catalyzed, tandem hydroperoxidation reaction. The absolute
      configuration of the cardamom peroxide is reported, and its mode of fragmentation
      following Fe(II)-mediated endoperoxide reduction is established. These studies
      reveal the generation of reactive intermediates distinct from previously studied
      endoperoxide natural products. 

PMID- 24673101
TI  - Structural and electronic properties of TM(n)[(BN)(3)H(6)](m) complexes with TM =
      Co (n, m = 1-3) and with TM = Fe, Ni, Ru, Rh, Pd (n = m = 1-3).
AB  - Using the density functional method with the generalized gradient approximation
      for the exchange and correlation, we investigated the geometrical and electronic
      properties of free-standing complexes of Con clusters combined with hydrogen
      saturated boron-nitrogen (BN) rings [(BN)3H6]m. The Co atoms tend to form a
      subcluster capped by BN rings that preserve the Co subcluster against the
      environment and with which they weakly interact. Thus, the Co subcluster is
      capable of sustaining a noticeable magnetic moment. These facts are relevant for
      designing grains with localized magnetic moments. We also optimized those
      TMn[(BN)3H6]n complexes with n = 1-3 and TM = Fe, Ni, Ru, Rh, and Pd, starting
      with the ground-state geometry obtained previously for TM = Co, in order to
      analyze the dependence of the electronic properties with the number of d
      electrons in the transition-metal atoms. 

PMID- 24673102
TI  - Anterior cruciate ligament injury after more than 20 years: I. Physical activity
      level and knee function.
AB  - Little is known about physical activity level and knee function including jump
      capacity and fear of movement/reinjury more than 20 years after injury of the
      anterior cruciate ligament (ACL). Seventy persons with unilateral ACL injury
      participated (23 +/- 2 years post-injury): 33 treated with physiotherapy in
      combination with surgical reconstruction (ACLR ), and 37 treated with
      physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched
      controls. Assessment included knee-specific and general physical activity level
      [Tegner activity scale, International Physical Activity Questionnaire (IPAQ)],
      knee function [Lysholm score, Knee injury and Osteoarthritis Outcome Score
      (KOOS)], jump capacity (one-leg hop, vertical jump, side hops), and fear of
      movement/reinjury [Tampa Scale for Kinesiophobia (TSK)]. Outcomes were related to
      degree of osteoarthritis (OA). ACL-injured had lower Lysholm, KOOS, and Tegner
      scores than controls (P < 0.001), while IPAQ score was similar. ACL-injured
      demonstrated inferior jump capacity in injured compared with noninjured leg (6
      25%, P < 0.001-P = 0.010 in the different jumps), while noninjured leg had equal
      jump capacity as controls. ACL groups scored 33 +/- 7 and 32 +/- 7 of 68 on TSK.
      Lower scores on Lysholm and KOOS symptom were seen for persons with moderate-to
      high OA than for no-or-low OA, while there were no differences for physical
      activity and jump capacity. Regardless of treatment, there are still negative
      knee-related effects of ACL injury more than 20 years later. 

PMID- 24673103
TI  - How to find the Ariadne's thread in the labyrinth of salvage treatment options
      for metastatic colorectal cancer?
AB  - Since a chance for cure was found out in metastatic colorectal cancer (mCRC)
      patients undergoing a resection of liver and lung metastases, high tumor
      shrinkage by chemotherapy regimens and their combination with targeted agents
      have been addressed in potentially resectable mCRC. However, most mCRC patients
      cannot reach this opportunity because of tumor burden or metastatic sites. For
      these patients a salvage systemic therapy could be offered to prolong survival.
      To date, a huge number of clinical trials provided some evidences for the
      achievement of this goal. A lot of chemotherapeutic regimens in combination with
      biological therapies are now available. We tried to propose a simple way to
      choose the best options and to plan an optimal sequence of treatments. This tool
      could help the oncologists worldwide to better and easily manage mCRC patients
      who need salvage systemic therapy. 

PMID- 24673104
TI  - Identification of novel HSP90alpha/beta isoform selective inhibitors using
      structure-based drug design. demonstration of potential utility in treating CNS
      disorders such as Huntington's disease.
AB  - A structure-based drug design strategy was used to optimize a novel benzolactam
      series of HSP90alpha/beta inhibitors to achieve >1000-fold selectivity versus the
      HSP90 endoplasmic reticulum and mitochondrial isoforms (GRP94 and TRAP1,
      respectively). Selective HSP90alpha/beta inhibitors were found to be equipotent
      to pan-HSP90 inhibitors in promoting the clearance of mutant huntingtin protein
      (mHtt) in vitro, however with less cellular toxicity. Improved tolerability
      profiles may enable the use of HSP90alpha/beta selective inhibitors in treating
      chronic neurodegenerative indications such as Huntington's disease (HD). A
      potent, selective, orally available HSP90alpha/beta inhibitor was identified
      (compound 31) that crosses the blood-brain barrier. Compound 31 demonstrated
      proof of concept by successfully reducing brain Htt levels following oral dosing
      in rats. 

PMID- 24673105
TI  - Gender differences in work-related asthma: surveillance data from California,
      Massachusetts, Michigan, and New Jersey, 1993-2008.
AB  - OBJECTIVE: To characterize work-related asthma by gender. METHODS: We analyzed
      state-based sentinel surveillance data on confirmed work-related asthma cases
      collected from California, Massachusetts, Michigan, and New Jersey during 1993
      2008. We used Chi-square and Fisher's Exact Test statistics to compare select
      characteristics between females and males. RESULTS: Of the 8239 confirmed work
      related asthma cases, 60% were female. When compared to males with work-related
      asthma, females with work-related asthma were more likely to be identified
      through workers' compensation (14.8% versus 10.6%) and less likely to be
      identified through hospital data (14.2% versus 16.9%). Moreover, when compared to
      males, females were more likely to have work-aggravated asthma (24.4% versus
      13.5%) and less likely to have new-onset asthma (48.0% versus 56.5%). Females
      were also more likely than males with work-related asthma to work in healthcare
      and social assistance (28.7% versus 5.2%), educational services (11.8% versus
      4.2%), and retail trade (5.0% versus 3.9%) industries and in office and
      administrative support (20.0% versus 4.0%), healthcare practitioners and
      technical (13.4% versus 1.6%), and education training and library (6.2% versus
      1.3%) occupations. Agent groups most frequently associated with work-related
      asthma were miscellaneous chemicals (20.3%), cleaning materials (15.3%), and
      indoor air pollutants (14.9%) in females and miscellaneous chemicals (15.7%),
      mineral and inorganic dusts (13.2%), and pyrolysis products (12.7%) in males.
      CONCLUSIONS: Among adults with work-related asthma, males and females differ in
      terms of workplace exposures, occupations, and industries. Physicians should
      consider these gender differences when diagnosing and treating asthma in working
      adults.

PMID- 24673106
TI  - Greenwoodochromini Takahashi from Lake Tanganyika is a junior synonym of
      Limnochromini poll (Perciformes: Cichlidae).
AB  - The infraorbitals (IOs) of four species endemic to Lake Tanganyika were examined
      and on the basis of this information and previous morphological and molecular
      studies, the tribe Greenwoodochromini is synonymized with the tribe Limnochromini
      and a new combination for Limnochromis abeelei and Limnochromis staneri is
      proposed: Greenwoodochromis abeelei and Greenwoodochromis staneri. The revised
      tribe Limnochromini, comprising 10 species belonging to seven genera, is
      characterized by IOs representing types G and I. The revised genus
      Greenwoodochromis, which consists of four species, is characterized by IOs
      representing type I. 

PMID- 24673107
TI  - Characterization of the emerging Salmonella 4,[5],12:i:- in Danish animal
      production.
AB  - The monophasic Salmonella variant with the antigenic formula Salmonella
      4,[5],12:i:- has emerged in the last decade as one of the main serotypes related
      to human salmonellosis. In the present study, a collection of 94 isolates of the
      S. 4,12:i:- and S. 4,5,12:i:- coming from Danish farm animals, swine (86), cattle
      (7), and poultry (1), with well-defined identification was further typed by
      polymerase chain reaction serotyping, phage typing, and molecular typing
      (polymerase chain reaction and multilocus variable-number tandem-repeat analysis
      [MLVA]). Moreover, the determination of antimicrobial resistance pattern of each
      isolate was tested. In 68 of the isolates the fljB gene was absent (i.e., they
      were true monophasic strains), whereas in 26 isolates, the gene was present
      despite the fact that the isolates did not express it. The results clustered the
      isolates in three main pulse-types. The predominant cluster was compatible with
      the previously described pattern STYMXB.0131. All the isolates included in this
      cluster lacked the fljB gene, and all the isolates except one belonged to phage
      type DT 193 with the AMP-STR-SMX-TET resistance pattern. MLVA analysis divided
      the clusters in several MLVA profiles previously reported by other studies.
      Finally, antimicrobial resistance and multiresistance was frequent, although no
      resistance was detected in critical compounds: fluoroquinolones and
      cephalosporins. The present study demonstrates the presence of monophasic
      Salmonella Typhimurium-like strains in Danish food animal production with well
      characterized clones that are described by previous studies, demonstrating the
      emergence and spread of this serotype in Denmark.

PMID- 24673108
TI  - Dramatic exacerbation of palmoplantar pustulosis following strongly positive
      nickel patch testing.

PMID- 24673110
TI  - Inclusion of urea in a 59FeEDTA solution stimulated leaf penetration and
      translocation of 59Fe within wheat plants.
AB  - The role of urea in the translocation of (59) Fe from (59) FeEDTA-treated leaves
      was studied in durum wheat (Triticum durum) grown for 2 weeks in nutrient
      solution and until grain maturation in soil culture. Five-cm long tips of the
      first leaf of young wheat seedlings or flag leaves at the early milk stage were
      immersed twice daily for 10 s in (59) FeEDTA solutions containing increasing
      amounts of urea (0, 0.2, 0.4 and 0.8% w/v) over 5 days. In the experiment with
      young wheat seedlings, urea inclusion in the (59) FeEDTA solution increased
      significantly translocation of (59) Fe from the treated leaf into roots and the
      untreated part of shoots. When (59) Fe-treated leaves were induced into
      senescence by keeping them in the dark, there was a strong (59) Fe translocation
      from these leaves. Adding urea to the (59) Fe solution did not result in an
      additional increase in Fe translocation from the dark-induced senescent leaves.
      In the experiment conducted in the greenhouse in soil culture until grain
      maturation, translocation of (59) Fe from the flag leaves into grains was also
      strongly promoted by urea, whereas (59) Fe translocation from flag leaves into
      the untreated shoot was low and not affected by urea. In conclusion, urea
      contributes to transportation of the leaf-absorbed Fe into sink organs. Probably,
      nitrogen compounds formed after assimilation of foliar-applied urea (such as
      amino acids) contributed to Fe chelation and translocation to grains in wheat.

PMID- 24673109
TI  - Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory
      CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid
      arthritis synovial fibroblasts.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic
      inflammation and synovial hyperplasia leading to progressive joint destruction.
      Fibroblast-like synoviocytes (FLS) are central components of the aggressive,
      tumour-like synovial structure termed pannus, which invades the joint space and
      cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory
      CD94/NKG2A receptor is present in RA synovial fluid. Little is known about
      possible cellular interactions between RA-FLS and NK cells. We used cultured RA
      FLS and the human NK cell line Nishi, of which the latter expresses an NK
      receptor repertoire similar to that of NK cells in RA synovial fluid, as an in
      vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express
      numerous ligands for both activating and inhibitory NK cell receptors, and
      stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and
      NKp44 are the key activating receptors involved in Nishi cell degranulation
      towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its
      ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co
      culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an
      in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell
      mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence
      local joint inflammation in RA. 

PMID- 24673111
TI  - Temporal definition of haematopoietic stem cell niches in a large animal model of
      in utero stem cell transplantation.
AB  - The fetal sheep model has served as a biologically relevant and translational
      model to study in utero haematopoietic stem cell transplantation (IUHSCT), yet
      little is known about the ontogeny of the bone marrow (BM) niches in this model.
      Because the BMmicroenvironment plays a critical role in the outcome of
      haematopoietic engraftment, we have established the correlation between the fetal
      sheep and fetal-human BM niche ontogeny, so that studies addressing the role of
      niche development at the time of IUHSCT could be accurately performed.
      Immunofluorescence confocal microscopic analysis of sheep fetal bone from
      gestational days (gd) 25-68 showed that the BM microenvironment commences
      development with formation of the vascular niche between 25 and 36 gd in sheep;
      correlating with the events at 10-11 gestational weeks (gw) in humans.
      Subsequently, between 45 and 51 gd in sheep (c. 14 gw in humans), the
      osteoblastic/endosteal niche started developing, the presence of CD34(+)  CD45(+)
      cells were promptly detected, and their number increased with gestational age.
      IUHSCT, performed in sheep at 45 and 65 gd, showed significant haematopoietic
      engraftment only at the later time point, indicating that a fully functional BM
      microenvironment improved engraftment. These studies show that sheep niche
      ontogeny closely parallels human, validating this model for investigating niche
      influence/manipulation in IUHSCT engraftment. 

PMID- 24673112
TI  - Impaired resolution of inflammation in human chronic heart failure.
AB  - BACKGROUND: Lipoxins (LXs) are proresolving and anti-inflammatory eicosanoids
      whose role in chronic heart failure (CHF) pathogenesis has never been
      investigated. This study evaluated levels of LXs in CHF patients, its
      relationship with disease severity and correlation with established CHF
      biomarkers. The effect of low-dose aspirin [acetylsalicylic acid (ASA)] on the
      levels of LXs was also studied. MATERIALS AND METHODS: Lipoxin A4 (LXA4 ), 15-epi
      lipoxin A4 (15-epi-LXA4 ) and myeloperoxidase (MPO) concentration and activity
      were evaluated by immunoenzymatic and spectrophotometric assays in 34 CHF
      patients [New York Heart Association (NYHA) functional class I to IV]. B-type
      natriuretic peptide (BNP), troponin, myoglobin, C-reactive protein (CRP) and uric
      acid (UA) were also analyzed. RESULTS: Patients were stratified into mild-to
      moderate CHF (NYHA, classes I and II) and severe CHF (NYHA classes III and IV).
      Severe patients had lower plasma LXA4 (0.262 +/- 0.034 vs. 0.362 +/- 0.039 ng/mL,
      P < 0.05) and decreased urinary 15-epi-LXA4 levels (2.28 +/- 0.44 vs. 4.88 +/-
      1.03 MUg/day, P < 0.05) besides exhibiting increased plasma BNP (1464 +/- 442 vs.
      555 +/- 162 pg/mL, P < 0.05) and MPO activity (45.15 +/- 11.56 vs. 15.90 +/- 2.80
      MUmol/min/mg protein, P < 0.05). Plasma LXA4 was inversely correlated with BNP,
      troponin, myoglobin, CRP, UA and MPO activity. ASA treatment was associated with
      higher urinary excretion of 15-epi-LXA4 (7.70 +/- 1.48 vs. 2.06 +/- 0.30 MUg/day,
      P < 0.05) in mild-to-moderate CHF patients and lower BNP levels in both groups.
      CONCLUSIONS: Higher severity of CHF is associated with reduced levels of LXs.
      Plasma LXA4 appears to be a valuable marker for risk stratification in CHF.
      Furthermore, the ASA-related increase in urinary 15-epi-LXA4 suggests enhanced
      renal synthesis of this eicosanoid and may represent a disregarded benefit of
      ASA.

PMID- 24673113
TI  - Transthoracic echocardiography in women with treated severe pre-eclampsia.
AB  - The aim of this study was to investigate cardiac function and haemodynamic
      indices using transthoracic echocardiography in women with severe pre-eclampsia
      who had already received treatment interventions. Fifteen women with treated
      severe pre-eclampsia were studied using transthoracic echocardiography. Mean (SD)
      cardiac output in women with treated disease was 5690 (1708) ml.min(-1). Systolic
      function was preserved in women with treated disease evidenced by mean (SD)
      fractional shortening 41 (9)%, fractional area change 62 (12)% and septal s'
      velocities 9.0 (2.1) cm.s(-1). Left ventricle end-diastolic diameters were within
      healthy reference ranges at 4.7 (0.3) cm and the left ventricle was not dilated.
      Diastolic function was reduced, with a mean (SD) mitral valve E/septal e' ratio
      of 12.6 (4.1). Left ventricular mass was increased at 182.0 (44.4) g. There was
      large variability in haemodynamics in women with treated severe pre-eclampsia.
      Transthoracic echocardiography is acceptable and applicable and enables
      quantification of cardiac function in women with severe pre-eclampsia.

PMID- 24673114
TI  - Effect of a new social support program by voluntary organization in pediatric
      oncology department in a developing country.
AB  - Comprehensive childhood cancer treatment in the modern era means not only
      strenuous treatment regimens and meticulous nursing care, it also implies
      attention to social, psychological, and financial aspects of disease and
      treatment. In a developing country like ours, though it is possible to provide
      good medical and nursing care in government set-up, there is always shortage of
      workforce and financial support, leading to nonadherence to treatment regimens by
      patients and parents, resulting in suboptimal treatment outcomes. Overcrowding of
      pediatric cancer patients along with general patients for lab tests and other
      hospital services, poor drug compliance, treatment abandonment, and lost to
      follow-up, lack of funding to meet nonmedical expenses and inadequate facility
      for providing psychological support were some of the major reasons we could
      identify as lacunae in our pediatric oncology division (POD). We introduced a new
      social support program with the help of additional staff supported by a
      nongovernmental agency, and new quality improvement services were introduced. The
      impact was demonstrable as reduction in waiting time in the hospital, allayed
      anxiety of painful procedures, better drug compliance, less treatment
      abandonment, and improved follow-up. This can be emulated in similar other
      resource-limited centers.

PMID- 24673115
TI  - Barriers to cure for children with cancer in India and strategies to improve
      outcomes: a report by the Indian Pediatric Hematology Oncology Group.
AB  - The survival of children with cancer in India is inferior to that of children in
      high-income countries. The Indian Pediatric Hematology Oncology Group (IPHOG)
      held a series of online meetings via www.Cure4kids.org to identify barriers to
      cure and develop strategies to improve outcomes. Five major hurdles were
      identified: delayed diagnosis, abandonment, sepsis, lack of co-operative groups,
      and relapse. Development of regional networks like IPHOG has allowed rapid
      identification of local causes of treatment failure for children with cancer in
      India and identification of strategies likely to improve care and outcomes in the
      participating centers. Next steps will include interventions to raise community
      awareness of childhood cancer, promote early diagnosis and referral, and reduce
      abandonment and toxic death at each center. Starting of fellowship programs in
      pediatric hemato-oncology, short training programs for pediatricians, publishing
      outcome data, formation of parent and patient support groups, choosing the right
      and effective treatment protocol, and setting up of bone marrow transplant
      services are some of the effective steps taken in the last decade, which needs to
      be supported further. 

PMID- 24673116
TI  - Learning visual units after brief experience in 10-month-old infants.
AB  - How does perceptual learning take place early in life? Traditionally, researchers
      have focused on how infants make use of information within displays to organize
      it, but recently, increasing attention has been paid to the question of how
      infants perceive objects differently depending upon their recent interactions
      with the objects. This experiment investigates 10-month-old infants' use of brief
      prior experiences with objects to visually organize a display consisting of
      multiple geometrically shaped three-dimensional blocks created for this study.
      After a brief exposure to a multipart portion of the display, each infant was
      shown two test events, one of which preserved the unit the infant had seen and
      the other of which broke that unit. Overall, infants looked longer at the event
      that broke the unit they had seen prior to testing than the event that preserved
      that unit, suggesting that infants made use of the brief prior experience to (a)
      form a cohesive unit of the multipart portion of the display they saw prior to
      test and (b) segregate this unit from the rest of the test display. This suggests
      that infants made inferences about novel parts of the test display based on
      limited exposure to a subset of the test display. Like adults, infants learn
      features of the three-dimensional world through their experiences in it.

PMID- 24673117
TI  - Formula-fed infants have significantly higher fat-free mass content in their
      bodies than breastfed babies.
AB  - AIM: Early nutrition may affect body composition development. This study assessed
      body composition changes in healthy term infants in the first four months of
      life, comparing the results for breastfed and formula-fed babies. METHODS: A
      longitudinal, observational study was conducted with healthy term infants, who
      had a birth weight of more than 2500 g and were aged up to 3 weeks at enrolment.
      Infants were either exclusively breastfed or formula-fed. Growth and body
      composition were assessed by air-displacement plethysmography at enrolment and 4
      months. RESULTS: A total of 158 infants were enrolled (72 exclusively breastfed
      and 86 exclusively formula-fed). Body composition was similar between the two
      feeding groups at enrolment, but fat-free mass (4831 +/- 538 g vs 4641 +/- 461 g;
      p = 0.036) at 4 months and the fat-free mass changes between enrolment and 4
      months (80.3 +/- 16.4% vs 67.6 +/- 18.4%; p < 0.001) were higher in formula-fed
      infants than breastfed ones. CONCLUSIONS: Our findings suggest that formula-fed
      infants show different body composition development during the first 4 months of
      life to breastfed ones, with higher fat-free mass content.

PMID- 24673118
TI  - Pneumatic tourniquet for surgical procedures of hemodialysis vascular access.
AB  - Pneumatic tourniquet has been frequently utilized in various surgical specialties
      to facilitate surgical procedures on the extremities. However, its use for
      surgical procedures of hemodialysis access has been limited to some surgeons in
      the United States and often confined to the hospital settings under general
      anesthesia or regional nerve block. We have successfully employed a pneumatic
      tourniquet system for surgical procedures of hemodialysis access under conscious
      sedation and local anesthesia in an outpatient setting. Because prolonged
      tourniquet inflation is associated with ischemic pain and other potential
      complications, we have limited the continuous inflation time to <30 minutes. Our
      recent data from 550 surgical procedures of hemodialysis access have emphasized
      that pneumatic tourniquet use is well tolerated under conscious sedation and not
      associated with significant adverse events. These and other reported data suggest
      that pneumatic tourniquet can reduce procedure time, minimize required
      dissection, reduce vascular trauma by eliminating vascular clamps and potentially
      improve the outcomes of surgical procedures of hemodialysis access. These
      advantages may be translated into cost savings for hemodialysis access care. This
      review discusses practical issues of pneumatic tourniquet use and its
      applications in surgical procedures of hemodialysis access. 

PMID- 24673119
TI  - Perceptual properties of feedback stimuli influence the feedback-related
      negativity in the flanker gambling task.
AB  - A negative deflection in the event-related potential is enhanced following error-
      and loss-related feedback in decision-making and simple gambling tasks.
      Researchers have assumed that the perceptual properties of the feedback stimuli
      are unimportant in explaining these effects. This assumption was tested in the
      present study through a flanker gambling task, in which the perceptual properties
      of the feedback were manipulated. Consistent with previous studies, loss elicited
      a larger feedback-related negativity (FRN) than gain feedback. However, this FRN
      reward effect was modulated by the perceptual properties of the feedback stimuli.
      When gain and loss feedback were perceptually similar to each other, the
      enhancement of the FRN following the loss feedback was smaller compared to when
      the gain and loss feedback were different from each other. In addition,
      incongruent feedback elicited a larger FRN than congruent feedback; this FRN
      congruency effect was larger following gain than loss feedback. These results
      suggested that perceptual properties of the feedback stimuli play a role in the
      elicitation of the FRN. 

PMID- 24673120
TI  - Plerixafor for mobilization of blood stem cells in autologous transplantation: an
      update.
AB  - INTRODUCTION: About 99% of all autologous transplants are now performed with
      blood stem cells. G-CSF alone or combined with chemotherapy have been used to
      mobilize CD34(+) cells. Plerixafor is a novel drug used for mobilization
      purposes. AREAS COVERED: We have evaluated recent data in regard to plerixafor
      use in predicted or proven poor mobilizers. In addition, we have looked for
      preemptive strategies to optimize the use of this expensive drug. Also cost
      efficacy issues and effects of plerixafor on graft composition and post
      transplant outcomes will be discussed. EXPERT OPINION: Plerixafor added to G-CSF
      is superior than G-CSF alone for mobilization of CD34(+) cells. This combination
      is also efficient in patients who have failed a previous mobilization attempt
      with other methods or in patients with risk factors for poor mobilization.
      Addition of plerixafor to G-CSF or chemotherapy plus G-CSF mobilization in
      patients who appear to mobilize poorly is under active investigation and
      algorithms for a preemptive use of this expensive agent have been proposed.
      Grafts collected after plerixafor appear to contain more lymphoid cells than the
      grafts collected without it. Whether this affects post-transplant outcomes such
      as immune reconstitution and risk of relapse needs to be evaluated.

PMID- 24673121
TI  - Direct-to-implant breast reconstruction: an analysis of 1612 cases from the ACS
      NSQIP surgical outcomes database.
AB  - There is continued debate about the outcomes of direct-to-implant (DTI) breast
      reconstruction when compared to a two-stage expander/implant approach. The
      purpose of this study was to examine outcomes after DTI reconstruction utilising
      the American College of Surgeons-National Surgical Quality Improvement (ACS
      NSQIP) database. This study reviewed the 2005-2010 ACS-NSQIP databases
      identifying encounters with common procedural terminology codes for DTI (19340)
      (mastectomy and immediate implant placement). A composite variable of "major
      surgical complications" (deep infection, return to OR, device loss) was used as
      the dependent variable in the analysis. Logistic regression analysis was
      performed to assess for pre- and intraoperative factors associated with the
      occurrence of "major surgical complications". Overall, 1612 patients underwent
      one stage, DTI reconstruction with an average age of 50.8 +/- 10.7 years with a
      body mass index (BMI) (kg/m2) of 26.9 +/- 6.3 kg/m2. The incidence of major
      surgical complications was 9%. A multivariate regression analysis revealed
      obesity (OR = 1.54, p = 0.03), active smoking (OR = 1.60, p = 0.044), and
      prolonged operative time (>1 SD above average) (OR = 1.88, p = 0.002) were
      associated with surgical morbidity. The results of the analysis emphasize that
      DTI-based breast reconstruction can be an excellent option for a specific group
      of patients. Careful pre-operative patient selection will optimise outcomes, and
      caution must be used in assessing suitability of DTI in obese patients and active
      smokers.

PMID- 24673122
TI  - Clinical analysis of risk factors of the patency of the descending branch of the
      lateral circumflex femoral artery.
AB  - Many studies have provided anatomical statistics of the descending branch of
      lateral circumflex femoral artery (LCFA) through its use as the pedicle of
      anterolateral thigh (ALT) flaps. However, most of the results from these studies
      were acquired during surgeries or from cadavers. Therefore, this study has
      studied the descending branch of LCFA in patients with underlying diseases or
      risk factors using lower extremity angiography, and how such risk factors and the
      degree of stenosis in other arteries affect the patency and stability of the
      descending branch. The subjects of retrospective study were 89 legs from 49
      patients who had received lower extremity angiography. Risk factors included age,
      BMI, diabetes, hypertension, tobacco use, hyperlipidemia, cardiac status, carotid
      status, renal disease, pulmonary status, and history of lower limb amputation.
      Analysis of the degree of stenosis in the descending branch of LCFA in regard to
      each risk factor have shown that hypertension, pulmonary function, history of
      lower limb amputation, and the total score of 11 risk factors were statistically
      significant. Also, in the correlation study of lower limb arteries, there was a
      significant correlation with the degree of stenosis in the posterior tibial
      artery, but not so in others. Therefore, when planning a flap surgery using the
      descending branch of LCFA, one needs to run imaging tests such as angiography to
      check arterial patency in patients with hypertension, impaired pulmonary
      function, and history of lower limb amputation.

PMID- 24673123
TI  - Relevance of chest radiography in pediatric inpatients with asthma.
AB  - INTRODUCTION: The goals of this study are to identify factors associated with
      ordering of chest radiographs (CXR's) in children hospitalized with acute asthma
      exacerbations and determine the overall clinical impact of these CXR's. METHODS:
      A retrospective study was performed with children >= 2 years of age admitted from
      our emergency department (ED) between 6/1/2011 and 5/31/2012 with a primary
      diagnosis of acute asthma exacerbation or status asthmaticus. Patients were
      excluded if they had been on antibiotics prior to the emergency visit, received
      continuous albuterol or intravenous magnesium during the hospitalization, or had
      another chronic disease affecting lung function. RESULTS: 180 of the 405 children
      in the study (44%) had CXR's ordered, of which 18 (10%) had imaging that altered
      the patient's treatment plan. There were six cases of radiologist-diagnosed
      pneumonia, nine cases of atelectasis treated with antibiotics and three cases of
      pneumothorax. Factors associated with CXR ordering were: fever at home or in the
      ED (OR 4.5, 95% CI 2.8-7.4), triage oxygen saturation less than or equal to 92%
      (OR 1.8, 95% CI 1.2-2.7) and age 4 years or less (OR 2.3, 95% CI 1.4-3.7).
      Patients with treatment-altering CXR's were more likely to have oxygen
      saturations less than or equal to 92% (OR 4.2, 95% CI 1.4-13.0; p = 0.006) or
      fever in the ED (OR 3.8, 95% CI 1.0-13.6; p < 0.05). No patients with triage
      oxygen saturation above 96% had a treatment-altering CXR. CONCLUSIONS: The
      majority of CXR's ordered in pediatric inpatients with asthma exacerbation do not
      provide clinically relevant information.

PMID- 24673124
TI  - Self-assemblies based on the "outer-surface interactions" of cucurbit[n]urils:
      new opportunities for supramolecular architectures and materials.
AB  - Supramolecular architectures and materials have attracted immense attention
      during the last decades because they not only open the possibility of obtaining a
      large variety of aesthetically interesting structures but also have applications
      in gas storage, sensors, separation, catalysis, and so on. On the other hand,
      cucurbit[n]urils (Q[n]s), a relatively new class of macrocyclic hosts with a
      rigid hydrophobic cavity and two identical carbonyl fringed portals, have
      attracted much attention in supramolecular chemistry. Because of the strong
      charge-dipole and hydrogen bonding interactions, as well as hydrophobic and
      hydrophilic effect derived from the negative portals and rigid cavities of Q[n]s,
      nearly all research in Q[n]s has been focused on utilizing the portals and
      cavities to construct supramolecular assemblies similar to other macrocyclic
      receptors such as cyclodextrin and calixarenes. Interestingly, a recent study
      revealed that other weak noncovalent interactions such as hydrogen bonding and
      pi...pi stacking, as well as C-H...pi and ion-dipole interactions, could also be
      defined as "outer-surface interactions", which are derived from the
      electrostatically positive outer surface of Q[n]s. These interactions could be
      the driving forces in the formation of various novel Q[n]-based supramolecular
      architectures and functional materials. In this Account, we provide a
      comprehensive overview of supramolecular self-assemblies based on the outer
      surface interactions of Q[n]s. These outer-surface interactions include those
      between Q[n]s, Q[n]s and aromatic molecules, Q[n]s and calixarenes, Q[n]s and
      inorganic complex ions, and Q[n]s and polyoxometalates. Pioneering work has shown
      that such weak noncovalent interactions play very important roles in the
      formation of various Q[n]-based functional materials and supramolecular
      architectures. For example, hydrogen bonds in outer-surface interactions between
      Q[n] molecules not only function as the sole driving force in the formation of
      one-dimensional Q[n] porous channels but also assist the bonding forces of the
      channels in capturing and accommodating acetylene molecules and carbon dioxide in
      the channel cavities. Moreover, upon introduction of a third species such as an
      aromatic molecule or inorganic anion into the Q[n]/metal system, "outer-surface
      interactions" could lead to Q[n]/metal-based self-assemblies from simple finite
      supramolecular coordination complexes to infinite polydimensional supramolecular
      architectures and other structures. Overall, this Account focuses on the novel
      self-assembly driving force derived from Q[n]s including (i) concepts of the
      outer-surface interactions of Q[n]s, (ii) providing plausible explanations of the
      mechanisms of the outer-surface interactions of Q[n]s, and (iii) introduction of
      an overview of the developments and practical applications of outer-surface
      interactions of Q[n]s in supramolecular chemistry. It is hoped that this study
      based on the outer-surface interactions of Q[n]s can enrich the field of
      molecular engineering of functional supramolecular systems and provide new
      opportunities for the construction of functional materials and architectures.

PMID- 24673125
TI  - Gold nanoparticles-based colorimetric assay for cathepsin B activity and the
      efficiency of its inhibitors.
AB  - Cathepsin B has been suggested to be a prognostic marker of melanoma, glioma, and
      a variety of cancers such as brain, breast, colon, esophageal, gastric, lung,
      ovarian, and thyroid cancers. Cathepsin B inhibitors have also been considered as
      anticancer drug candidates; hence, there has been a growing need for a probe
      which enables the selective and simple detection of cathepsin B and its
      inhibitors. For the purpose of selective assay, a cathepsin B-specific substrate,
      N,N'-diBoc-dityrosine-glycine-phenylalanine-3-(methylthio)propylamine (DBDY-Gly
      Phe-MTPA) was synthesized in this study. Phe-MTPA, which was produced via
      cathepsin B-catalyzed hydrolysis of DBDY-Gly-Phe-MTPA, allowed aggregation of
      gold nanoparticles (AuNPs) leading to a color change from red to blue. When
      tested for cathepsins B, L, and S, this assay method exhibited AuNPs color change
      only in reaction to cathepsin B. The limits of detection for cathepsin B was 10
      and 5 nM in the 1 and 2 h hydrolysis reactions, respectively. The efficiency of
      cathepsin B inhibitors such as leupeptin, antipain, and chymostatin was easily
      compared by the degree of color change. Moreover, IC50 values of leupeptin,
      antipain, and chymostatin were found to be 0.11, 0.48, and 1.78 MUM,
      respectively, which were similar to the results of previous studies. Therefore
      the colorimetric assay of cathepsin B and cathepsin B inhibitors using DBDY-Gly
      Phe-MTPA and AuNPs allowed not only the selective but also the simple assay of
      cathepsin B and its inhibitors, which was possible with the naked eye. 

PMID- 24673127
TI  - A capture-recapture model of amphidromous fish dispersal.
AB  - Adult movement scale was quantified for two tropical Caribbean diadromous fishes,
      bigmouth sleeper Gobiomorus dormitor and mountain mullet Agonostomus monticola,
      using passive integrated transponders (PITs) and radio-telemetry. Large numbers
      of fishes were tagged in Rio Mameyes, Puerto Rico, U.S.A., with PITs and
      monitored at three fixed locations over a 2.5 year period to estimate transition
      probabilities between upper and lower elevations and survival probabilities with
      a multistate Cormack-Jolly-Seber model. A sub-set of fishes were tagged with
      radio-transmitters and tracked at weekly intervals to estimate fine-scale
      dispersal. Changes in spatial and temporal distributions of tagged fishes
      indicated that neither G. dormitor nor A. monticola moved into the lowest,
      estuarine reaches of Rio Mameyes during two consecutive reproductive periods,
      thus demonstrating that both species follow an amphidromous, rather than
      catadromous, migratory strategy. Further, both species were relatively sedentary,
      with restricted linear ranges. While substantial dispersal of these species
      occurs at the larval stage during recruitment to fresh water, the results
      indicate minimal dispersal in spawning adults. Successful conservation of
      diadromous fauna on tropical islands requires management at both broad basin and
      localized spatial scales. 

PMID- 24673126
TI  - 1alpha,25-dihydroxyvitamin D3 in combination with transforming growth factor-beta
      increases the frequency of Foxp3+ regulatory T cells through preferential
      expansion and usage of interleukin-2.
AB  - A high prevalence of vitamin D insufficiency and deficiency exists worldwide,
      which is associated with an increased incidence and severity of a range of immune
      mediated diseases. This has resulted in considerable interest in the
      immunodulatory functions of vitamin D. The active form of vitamin D, 1alpha,25
      dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to increase the frequency of
      Foxp3(+) CD4(+) T regulatory (Treg) cells when present at high concentrations or
      under strong T-cell stimulation in culture. Supporting evidence exists in vivo
      for a positive association between serum 25(OH)D and Foxp3(+) Treg cell numbers
      in humans. The aim of this work was to identify the cytokine milieu required in
      vitro to promote Foxp3(+) Treg cells in cultures containing 1,25(OH)2D3 at more
      moderate concentrations (10(-7) M). Stimulation of human CD4(+) T cells with a
      combination of 1,25(OH)2D3 and transforming growth factor-beta (TGF-beta) greatly
      increased the frequency of Foxp3(+) Treg cells, which is proposed to result from
      the preferential expansion of Foxp3(+) Treg cells, as compared with the Foxp3(-)
      effector T cells, in culture. The differential effect on proliferation may result
      from enhanced availability and usage of interleukin-2 by the Foxp3(+) Treg cells
      compared with Foxp3(-) effector T cells. In summary, modulation of the cytokine
      environment to one high in TGF-beta in the presence of 1,25(OH)2D3(10(-7) M)
      significantly increased Foxp3(+) Treg cell frequency. These data provide
      additional evidence for the important immunomodulatory properties of 1,25(OH)2D3
      that exist and may help to control inflammatory diseases.

PMID- 24673128
TI  - Reporting doping in sport: national level athletes' perceptions of their role in
      doping prevention.
AB  - This paper qualitatively explores national level athletes' willingness to report
      doping in sport. Following ethical approval, semi-structured interviews were
      conducted with nine national level athletes from rugby league (n = 5) and track
      and field athletics (n = 4). Thematic analysis established the main themes within
      the data. Contextual differences existed around the role that athletes perceived
      they would play if they became aware of doping. Specifically, track and field
      athletes would adopt the role of a whistle-blower and report individuals who were
      doping in their sport. In comparison, the rugby league players highlighted a
      moral dilemma. Despite disagreeing with their teammates' actions, the players
      would adhere to a code of silence and refrain from reporting doping. Taking these
      findings into account, prevention programs might focus on changing broader group
      and community norms around doping. In doing so, community members' receptivity to
      prevention messages may increase. Moreover, developing skills to intervene (e.g.,
      speaking out against social norms that support doping behavior) or increasing
      awareness of reporting lines could enhance community responsibility for doping
      prevention. In sum, the findings highlight the need to consider the context of
      sport and emphasize that a one-size-fits-all approach to anti-doping is
      problematic. 

PMID- 24673129
TI  - A threshold theory account of psychometric functions with response confidence
      under the balance condition.
AB  - The study of thresholds for discriminability has been of long-standing interest
      in psychophysics. While threshold theories embrace the concept of discrete-state
      thresholds, signal detection theory discounts such a concept. In this paper we
      concern ourselves with the concept of thresholds from the discrete-state
      modelling viewpoint. In doing so, we find it necessary to clarify some
      fundamental issues germane to the psychometric function (PF), which is
      customarily constructed using psychophysical methods with a binary-response
      format. We challenge this response format and argue that response confidence also
      plays an important role in the construction of PFs, and thus should have some
      impact on threshold estimation. We motivate the discussion by adopting a three
      state threshold theory for response confidence proposed by Krantz (1969, Psychol.
      Rev., 76, 308-324), which is a modification of Luce's (1963, Psychol. Rev., 70,
      61-79) low-threshold theory. In particular, we discuss the case in which the
      practice of averaging over order (or position) is enforced in data collection.
      Finally, we illustrate the fit of the Luce-Krantz model to data from a line
      discrimination task with response confidence. 

PMID- 24673130
TI  - Discovery of selective 4-Amino-pyridopyrimidine inhibitors of MAP4K4 using
      fragment-based lead identification and optimization.
AB  - Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is a
      serine/threonine kinase implicated in the regulation of many biological
      processes. A fragment-based lead discovery approach was used to generate potent
      and selective MAP4K4 inhibitors. The fragment hit pursued in this article had
      excellent ligand efficiency (LE), an important attribute for subsequent
      successful optimization into drug-like lead compounds. The optimization efforts
      eventually led us to focus on the pyridopyrimidine series, from which 6-(2
      fluoropyridin-4-yl)pyrido[3,2-d]pyrimidin-4-amine (29) was identified. This
      compound had low nanomolar potency, excellent kinase selectivity, and good in
      vivo exposure, and demonstrated in vivo pharmacodynamic effects in a human tumor
      xenograft model. 

PMID- 24673131
TI  - In this issue - April 2014: Perceptions of 2007 equine influenza outbreak .
      Hyperinsulinaemia in ponies . Hydration and perennial ryegrass toxicosis . Travel
      history needed for possible canine leishmaniosis . Complications of arthroscopy .
      Metaphyseal osteopathy in Kelpies . Infectious bronchitis virus and egg quality.

PMID- 24673133
TI  - Survey of Australian equine veterinarians evaluating their biosecurity training
      and perceptions and opinions about the management of the 2007 equine influenza
      outbreak.
AB  - OBJECTIVES: To evaluate the level of biosecurity training among Australian equine
      veterinarians and to assess their perceptions of biosecurity and infectious
      disease risk and their opinions about the management of the 2007 equine influenza
      (EI) outbreak. DESIGN: Cross-sectional study. METHODS: A survey was conducted
      among equine veterinarians attending the 2010 annual conference of the Equine
      Veterinarians Australia (EVA) in New South Wales, Australia. Data were collected
      using a self-completed questionnaire and analysed using Fisher's exact tests to
      assess veterinarians' levels of biosecurity training, their perceptions of
      infectious disease and views regarding the 2007 EI outbreak management. RESULTS:
      A total of 46 of the 196 (23.5%) attending veterinarians completed the
      questionnaire. Significantly greater proportions of recently graduated
      veterinarians received theoretical and practical biosecurity training at
      veterinary schools than their older counterparts. The majority of respondents
      considered their likelihood of spreading infectious diseases from one client's
      horse to another to be low (84%). More than half (58%) of the veterinarians
      considered that hand-washing/wearing gloves was very effective in preventing
      disease spread. However, around one-quarter (27%) reported a degree of
      reservation about the practicality of performing general biosecurity practices in
      everyday working life. Overall, veterinarians were satisfied with the EI outbreak
      response, but had mixed opinions about the control measures and communications
      used. CONCLUSION: Levels of biosecurity training and the frequency of biosecurity
      advice provided by veterinarians have increased over time, although the
      practicality of biosecurity practices is a concern for some veterinarians.
      Further investigations of the barriers to the use of various biosecurity
      practices are required in order to inform training programs.

PMID- 24673134
TI  - Percy Edwin Sykes: 1920-2014.

PMID- 24673135
TI  - Prevalence and risk factors for hyperinsulinaemia in ponies in Queensland,
      Australia.
AB  - OBJECTIVES: To determine the prevalence of hyperinsulinaemia in a population of
      ponies in Queensland, Australia, and identify associated factors. METHODS:
      Breeders or traders of ponies within a 100 km radius of Gatton, Queensland, were
      recruited for study using an internet database. Clinical and management details
      were obtained, including body condition score, fat deposition and history or
      evidence of laminitis. Blood samples were analysed for serum insulin and
      triglyceride concentrations and plasma adrenocorticotrophic hormone (ACTH) and
      leptin concentrations following short-term removal from pasture and withholding
      of supplementary food for at least 12 h. RESULTS: Of 23 pony studs identified, 22
      were available for visit. The study population consisted of 208 ponies: 70
      Australian Ponies; 67 Welsh Mountain Ponies or Cobs; 51 Connemara Ponies; 20
      Shetland ponies. We excluded 20 with suspected pituitary pars intermedia
      dysfunction (>15 years, ACTH >50 pg/mL). In total, 27% of the ponies (51/188)
      were hyperinsulinaemic (insulin >20 MUIU/mL). The final multivariable model
      revealed increasing age, supplementary feeding and increased leptin and
      triglyceride concentrations to be associated with hyperinsulinaemia. CONCLUSIONS:
      Hyperinsulinaemia was prevalent and associated with age and evidence of metabolic
      disturbance, including elevated leptin and triglyceride concentrations, in this
      population. A significant number of ponies were at risk of hyperinsulinaemia,
      which has implications for strategies to reduce the risk of laminitis in this
      population.

PMID- 24673136
TI  - Evidence of dehydration and electrolyte disturbances in cases of perennial
      ryegrass toxicosis in Australian sheep.
AB  - CASE REPORT: Perennial ryegrass toxicosis (PRGT) is a common disease entity in
      Australia, presenting as an association of clinical signs including alterations
      in normal behavioural, ataxia ('staggers'), ill thrift and gastrointestinal
      dysfunction ('scours'). Clinical signs can range in severity from mild (gait
      abnormalities and failure to thrive) to severe (seizures, lateral recumbency and
      death). Presentation across the flock is usually highly variable. PRGT is caused
      by toxins produced by the endophytic fungus Neotyphodium lolii, a symbiont of
      perennial ryegrass that is present in pastures across the temperate regions of
      Australia and Tasmania. A particular feature of PRGT in Australia is the
      occasional occurrence of large-scale sheep losses, suggesting other factors are
      influencing mortality rates compared with other PRGT risk zones such as North
      America and New Zealand. During 2011, producers in the state of Victoria
      experienced a mild outbreak of PRGT that affected large numbers of animals but
      with limited mortalities. Clinical samples taken from affected sheep showed a
      high incidence of dehydration and electrolyte abnormalities. CONCLUSION: We
      speculate that changes in hydration status may be a contributory aetiological
      factor in those years in which high numbers of deaths are associated with PRGT
      outbreaks in Australia.

PMID- 24673137
TI  - David Sutcliffe Wishart ISO BVSc: 1916-2013.

PMID- 24673138
TI  - Metaphyseal osteopathy in three Australian Kelpie siblings.
AB  - CASE REPORT: Metaphyseal osteopathy (MO) was diagnosed in three Australian Kelpie
      puppies that were presented for veterinary assessment of lameness. The three
      puppies were siblings. Each was from a different litter by the same breeding
      pair. The puppy in case one was seen by the authors, and the puppies in cases two
      and three were patients at other veterinary hospitals. However, the medical
      records and radiographs were examined and reviewed for this report. Radiographic
      investigation of the lameness revealed pathognomonic appearance of MO affecting
      the metaphyseal region of the long bones in all three puppies. The diagnosis was
      confirmed on histopathology in one patient. CONCLUSION: MO is considered a
      disease of large and giant-breed dogs, being rarely reported in non-large-breed
      dogs, and has not been reported in the Australian Kelpie, which is considered a
      medium-breed dog. This case series suggests a previously unreported breed
      predisposition to MO in the Australian Kelpie.

PMID- 24673139
TI  - Remaining vigilant for the exotic: cases of imported canine leishmaniosis in
      Australia 2000-2011.
AB  - BACKGROUND: Canine leishmaniosis (CL) caused by Leishmania infantum is a disease
      of worldwide importance, not only because it causes severe and potentially fatal
      disease in dogs, but also because of its zoonotic relevance. The parasite is the
      causative agent of human visceral leishmaniosis, a severe, debilitating disease
      that causes an estimated 59,000 deaths annually. Australia is considered to be
      free of zoonotic leishmaniosis. METHODS: A retrospective case series of five
      imported dogs diagnosed with CL between 2000 and 2011. Cases were identified by
      word-of-mouth and by referral. RESULTS: The dogs were diagnosed with CL between
      2000 and 2011; clinical, clinicopathological, and serological data are presented,
      together with a review of the disease and its biosecurity implications for
      Australia. CONCLUSIONS: Because of the unique immunopathology and diagnostic
      challenges associated with CL, the importance of obtaining a travel history is
      reinforced because some dogs imported prior to 2006 may develop clinical signs of
      this disease and present for veterinary examination. Furthermore, it is possible
      for leishmaniosis to become established within Australia under certain
      circumstances.

PMID- 24673140
TI  - Instrument breakage as a complication of elbow arthroscopy in a dog.
AB  - CASE REPORT: We describe an unusual complication of a routine arthroscopic
      procedure to treat fragmentation of the medial portion of the coronoid process in
      a 1-year-old Labrador Retriever. While the lesion was being curetted, the tip of
      the arthroscopic curette broke off. Attempts were made to remove it, but failed,
      and the broken fragment migrated out of the arthroscopic field. Conversion from
      arthroscopy to arthrotomy was unsuccessful. On intraoperative radiographs, the
      metallic fragment was detected in the radial fossa of the humeral condyle. A
      limited surgical approach to this area, guided by ultrasound, also proved
      ineffective. Finally, the broken curette tip was left in situ. The dog made an
      uneventful recovery and 6 months after surgery it showed no lameness except after
      rest and there was no evidence of migration of the metallic fragment on
      radiographs. CONCLUSIONS: On such occasions, we recommend: (1) stop both the
      inflow and outflow of fluids; (2) attempt arthroscopic retrieval with a magnetic
      retriever and large forceps; (3) use diagnostic imaging to localise the broken
      fragment if it migrates out of the arthroscopic field; and (4) leave in situ if
      it is no longer accessible to arthroscopic extraction. This is the first report
      of an instrument breakage during arthroscopy in a dog.

PMID- 24673141
TI  - Assessment of the potential relationship between egg quality and infectious
      bronchitis virus infection in Australian layer flocks.
AB  - OBJECTIVE: This investigation aimed to determine if there was a relationship
      between the production of eggs with poor internal quality, as measured by poor
      Haugh units, by Australian layer flocks and the detection of infectious
      bronchitis virus (IBV) in the hens. Other risk factors including flock size,
      flock type, flock age, chicken breed and vaccination frequency were also
      assessed. METHODS: The study group comprised 17 flocks from 14 farms. Data
      relating to the factors investigated were requested on a regular basis. The Haugh
      unit data were used to grade eggs as good or poor based on the age and flock at
      the time of data collection. Cloacal swabs were collected from 20 chickens in
      each flock approximately every 6 weeks. RESULTS: IBV was detected from a majority
      of the flocks and in 68% of cases the IBV strain detected was an A-vaccine
      related field strain. Three variant strains were detected. Detection of IBV in a
      flock, the farm type and flock size were identified as potential risk factors for
      the production of eggs with poor Haugh units. CONCLUSION: IBV is prevalent in
      Australian layer flocks, but infection was primarily subclinical. The results
      complement previous reports indicating that there are many potential risk factors
      for the production of eggs with poor Haugh units.

PMID- 24673143
TI  - Motion compensation for in vivo subcellular optical microscopy.
AB  - In this review, we focus on the impact of tissue motion on attempting to conduct
      subcellular resolution optical microscopy, in vivo. Our position is that tissue
      motion is one of the major barriers in conducting these studies along with light
      induced damage, optical probe loading as well as absorbing and scattering effects
      on the excitation point spread function and collection of emitted light. Recent
      developments in the speed of image acquisition have reached the limit, in most
      cases, where the signal from a subcellular voxel limits the speed and not the
      scanning rate of the microscope. Different schemes for compensating for tissue
      displacements due to rigid body and deformation are presented from tissue
      restriction, gating, adaptive gating and active tissue tracking. We argue that
      methods that minimally impact the natural physiological motion of the tissue are
      desirable because the major reason to perform in vivo studies is to evaluate
      normal physiological functions. Towards this goal, active tracking using the
      optical imaging data itself to monitor tissue displacement and either
      prospectively or retrospectively correct for the motion without affecting
      physiological processes is desirable. Critical for this development was the
      implementation of near real time image processing in conjunction with the control
      of the microscope imaging parameters. Clearly, the continuing development of
      methods of motion compensation as well as significant technological solutions to
      the other barriers to tissue subcellular optical imaging in vivo, including
      optical aberrations and overall signal-to-noise ratio, will make major
      contributions to the understanding of cell biology within the body.

PMID- 24673144
TI  - What all physicians should know about the potential radiation risk that computed
      tomography poses for paediatric patients.
AB  - The repeated use of CT imaging raises a child's radiation exposure, overall
      radiation accrual and future cancer risks. However, our review suggests that
      these risks can be considerably reduced by physicians, radiologists and academic
      bodies, through proper justification, optimisation and dose limitation.
      CONCLUSION: Computed tomography poses a potential risk of radiation-induced
      cancer in children. The physician must weigh up the overall risks and benefits of
      CT before referring a child for imaging.

PMID- 24673145
TI  - Unidentified drugs in traditional medications causing toxic epidermal necrolysis:
      a developing country experience.
AB  - BACKGROUND: Drugs are by far the most common cause of toxic epidermal necrolysis
      (TEN), but unidentified drugs and chemicals present in herbal and traditional
      medications may also be responsible for this reaction, which manifests as
      widespread epidermal detachment of the skin and mucous membrane. In contexts in
      which a subject has used an herbal or traditional medication, it is very
      difficult to diagnose the condition, identify the offending agent, and prevent
      the disease from recurring. METHODS: This prospective study was conducted at a
      tertiary burn center between July 2004 and October 2012. All patients were
      referred to this unit by the local department of medicine at least one week after
      the eruption of vesicles. On arrival, all patients demonstrated a severe form of
      disease with features of sepsis and electrolyte imbalance (SCORTEN scores of
      >=4). All non-fatal cases were followed to observe long-term sequelae and
      recurrences. RESULTS: About 34% of patients had developed the condition after
      ingesting traditional herbal medications and were unable to identify the
      responsible drug by name. Nineteen (66%) of the 29 patients referred to the unit
      with TEN died within the first week after being transferred. Nine patients
      achieved complete recovery, and one developed corneal haziness and alopecia. One
      patient experienced recurrence within three months but recovered. CONCLUSIONS:
      Illiteracy and financial vulnerability were major factors in driving patients
      towards the use of traditional medications, which were often prepared and
      preserved improperly. Mortality and other complications could be reduced by the
      prompt recognition of the condition, immediate withdrawal of the culprit drug,
      and quick referral to proper care.

PMID- 24673147
TI  - Making sense of the amyloid precursor protein: its tail tells an interesting
      tale.

PMID- 24673146
TI  - Assessment of resident and fellow knowledge of the organ donor referral process.
AB  - Maximizing deceased donation rates can decrease the organ shortage. Non
      transplant physicians play a critical role in facilitating conversion of
      potential deceased donors to actual donors, but studies suggest that physicians
      lack knowledge about the organ donation process. As residency and fellowship are
      often the last opportunities for formal medical training, we hypothesized that
      deficiencies in knowledge might originate in residency and fellowship. We
      conducted a cross-sectional survey to assess knowledge about organ donation,
      experience in donor conversion, and opinions of the process among residents and
      fellows after their intensive care unit rotations at the Johns Hopkins Hospital.
      Of 40 participants, 50% had previously facilitated donor conversion, 25% were
      familiar with the guidelines of the organ procurement organization (OPO), and 10%
      had received formal instruction from the OPO. The median score on the knowledge
      assessment was five of 10; higher knowledge score was not associated with level
      of medical training, prior training in or experience with donor conversion, or
      with favorable opinions about the OPO. We identified a pervasive deficit in
      knowledge among residents and fellows at an academic medical center with an
      active transplant program that may help explain attending-level deficits in
      knowledge about the organ donation process. 

PMID- 24673148
TI  - Transcendental experiences during meditation practice.
AB  - This article explores transcendental experiences during meditation practice and
      the integration of transcendental experiences and the unfolding of higher states
      of consciousness with waking, dreaming, and sleeping. The subject/object
      relationship during transcendental experiences is characterized by the absence of
      time, space, and body sense--the framework that gives meaning to waking
      experiences. Physiologically, transcendental experiences during Transcendental
      Meditation practice are marked by slow inhalation, along with autonomic
      orientation at the onset of breath changes and heightened alpha1 (8-10 Hz)
      frontal coherence. The integration of transcendental experiences with waking,
      dreaming, and sleeping is also marked by distinct subjective and objective
      markers. This integrated state, called Cosmic Consciousness in the Vedic
      tradition, is subjectively marked by inner self-awareness coexisting with waking,
      sleeping, and dreaming. Physiologically, Cosmic Consciousness is marked by the
      coexistence of alpha1 electroencephalography (EEG) with delta EEG during deep
      sleep, and higher brain integration, greater emotional stability, and decreased
      anxiety during challenging tasks. Transcendental experiences may be the engine
      that fosters higher human development.

PMID- 24673149
TI  - Meditation research, past, present, and future: perspectives from the Nalanda
      contemplative science tradition.
AB  - This article offers an overview of meditation research: its history, recent
      developments, and future directions. As the number and scope of studies grow, the
      field has converged with cognitive and affective neuroscience, and spawned many
      clinical applications. Recent work has shed light on the mechanisms and effects
      of diverse practices, and is entering a new phase where consensus and coherent
      paradigms are within reach. This article suggests an unusual path for future
      advancement: complementing conventional research with rigorous dialogue with the
      contemplative traditions that train expert meditators and best know the
      techniques. It explores the Nalanda tradition developed in India and preserved in
      Tibet, because its cumulative approach to contemplative methods produced a
      comprehensive framework that may help interpret data and guide research, and
      because its naturalistic theories and empirical methods may help bridge the gulf
      between science and other contemplative traditions. Examining recent findings and
      models in light of this framework, the article introduces the Indic map of the
      central nervous system and presents three testable predictions based on it.
      Finally, it reviews two studies that suggest that the multimodal Nalanda approach
      to contemplative learning is as well received as more familiar approaches, while
      showing promise of being more effective. 

PMID- 24673151
TI  - Applying a verification classification system to medical and forensic digital
      images.
AB  - This paper gives the definitions, and describes the application, of a
      classification system for photographic veracity relating to medical and forensic
      images. It uses practical examples to demonstrate the reasons and parameters for
      using such a system. It also calls for continued discussion on what the limits
      and extent should be for the parameters. A debate encompassing the advantages and
      disadvantages of manipulating photographs goes back well before the introduction
      of digital imaging and has continued since the introduction of photography in the
      mid-nineteenth century. This author's first foray dates back twenty years (1).
      The introduction of digital imaging only gave the debate new impetus and new
      problems to solve (2), some of which might be resolved as suggested in this
      paper.

PMID- 24673150
TI  - Meditative analgesia: the current state of the field.
AB  - Since the first demonstrations that mindfulness-based therapies could have a
      positive influence on chronic pain patients, numerous studies have been conducted
      with healthy individuals in an attempt to understand meditative analgesia. This
      review focuses explicitly on experimental pain studies of meditation and attempts
      to draw preliminary conclusions based on the work completed in this new field
      over the past 6 years. Dividing meditative practices into the broad categories of
      focused attention (FA) and open monitoring (OM) techniques allowed several
      patterns to emerge. The majority of evidence for FA practices suggests they are
      not particularly effective in reducing pain. OM, on the other hand, seems to
      influence both sensory and affective pain ratings depending on the tradition or
      on whether the practitioners were meditating. The neural pattern underlying pain
      modulation during OM suggests meditators actively focus on the noxious
      stimulation while inhibiting other mental processes, consistent with descriptions
      of mindfulness. A preliminary model is presented for explaining the influence of
      mindfulness practice on pain. Finally, the potential analgesic effect of the
      currently unexplored technique of compassion meditation is discussed. 

PMID- 24673152
TI  - Aromatic amide and hydrazide foldamer-based responsive host-guest systems.
AB  - CONSPECTUS: In host-guest chemistry, a larger host molecule selectively and
      noncovalently binds to a smaller guest molecule or ion. Early studies of host
      guest chemistry focused on the recognition of spherical metal or ammonium ions by
      macrocyclic hosts, such as cyclic crown ethers. In these systems, preorganization
      enables their binding sites to cooperatively contact and attract a guest.
      Although some open-chain crown ether analogues possess similar, but generally
      lower, binding affinities, the design of acyclic molecular recognition hosts has
      remained challenging. One of the most successful examples was rigid molecular
      tweezers, acyclic covalently bonded preorganized host molecules with open
      cavities that bind tightly as they stiffen. Depending on the length of the atomic
      backbones, hydrogen bonding-driven aromatic amide foldamers can form open or
      closed cavities. Through rational design of the backbones and the introduction of
      added functional groups, researchers can regulate the shape and size of the
      cavity. The directionality of hydrogen bonding and the inherent rigidity of
      aromatic amide units allow researchers to predict both the shape and size of the
      cavity of an aromatic amide foldamer. Therefore, researchers can then design
      guest molecules with structure that matches the cavity shape, size, and binding
      sites of the foldamer host. In addition, because hydrogen bonds are dynamic,
      researchers can design structures that can adapt to outside stimuli to produce
      responsive supramolecular architectures. In this Account, we discuss how aromatic
      amide and hydrazide foldamers induced by hydrogen bonding can produce responsive
      host-guest systems, based on research by our group and others. First we highlight
      the helical chirality induced as binding occurs in solution, which includes the
      induction of helicity by chiral guests in oligomeric and polymeric foldamers, the
      formation of diastereomeric complexes between chiral foldamer hosts and guests,
      and the induction of helical chirality by chiral guests into inherently flexible
      backbones. In addition, molecular or ion-pair guests can produce supramolecular
      helical chirality in the organogel state. Such structures exhibit remarkable time
      dependence and a "Sergeants and Soldiers" effect that are not observed for other
      two-component organogels that have been reported. We further illustrate that the
      reversible folding behavior of an aromatic amide foldamer segment can modulate
      the switching behavior of donor-acceptor interaction-based [2]rotaxanes. Finally
      we show that a folded oligomer can induce folding in one or two attached
      intrinsically flexible oligomers, an example of a solvent-responsive
      intramolecular host-guest system.

PMID- 24673153
TI  - How to use health and nutrition-related claims correctly on food advertising:
      comparison of benefit-seeking, risk-avoidance, and taste appeals on different
      food categories.
AB  - This study applies the concepts of health halos and unhealthy = tasty intuition
      to examine how the different health and nutrition-related (HNR) appeal types
      interact with different food product types compared with taste claims. The
      experiment investigated the impact of benefit-seeking and risk-avoidance HNR
      appeals compared with that of taste appeals on different food types. The authors
      found that although respondents evaluated food ads with the two HNR appeals as
      less risky/more beneficial and healthier than food ads with a taste claim, the
      respondents showed better ad-related evaluations on the HNR appeals for
      perceivably healthy food and on taste appeal for perceivably unhealthy food. The
      findings provide several theoretical and practical implications for health food
      marketing and public health policy.

PMID- 24673154
TI  - Increased mitochondrial electron transport chain activity at complex I is
      regulated by N-acetylcysteine in lymphocytes of patients with systemic lupus
      erythematosus.
AB  - AIMS: Systemic lupus erythematosus (SLE) patients' peripheral blood lymphocytes
      (PBL) show mitochondrial dysfunction and oxidative stress. To determine the
      electrochemical bases of mitochondrial dysfunction, we measured electron
      transport chain (ETC) activity and its regulation by N-acetylcysteine (NAC) that
      reversed glutathione depletion and improved disease activity in SLE. ETC activity
      was assessed in PBL of 69 SLE patients and 37 healthy donors. Negatively isolated
      T cells were examined in 7 SLE patients, 11 healthy donors, and 10 nonlupus
      inflammatory arthritis (IA) donors. RESULTS: O2 consumption (in nmol/ml/min) by
      lupus PBL was increased at baseline (SLE: 2.492+/-0.196, control: 2.137+/-0.153;
      p=0.027) and with complex IV substrates (SLE: 7.722+/-0.419, control: 7.006+/
      0.505; p=0.028). SLE PBL consumed more O2 upon in-chamber T-cell activation
      (p=0.012). After overnight T-cell stimulation, ETC activity of SLE PBL was 2.27
      fold increased through complex I (SLE: 1.606+/-0.273, control: 0.709+/-0.169;
      p=0.001) and, to a lesser extent, through complex IV. Likewise, complex I
      activity was elevated in negatively isolated "untouched" T cells of SLE patients
      (1.816+/-0.180) relative to healthy controls (0.917+/-0.094; p=0.0003) and IA
      disease controls studied in parallel (1.057+/-0.199; p=0.0308). NAC diminished O2
      consumption through complex I and H2O2 levels both in SLE and in control PBL.
      INNOVATION: O2 consumption was found to be increased in SLE patients' PBL
      relative to control subjects evaluated in parallel. ETC complex I is identified
      as the main source of oxidative stress in SLE. CONCLUSIONS: Lupus PBL exhibit
      increased O2 consumption through mitochondrial ETC complex I that is inhibited by
      NAC, which may have therapeutic efficacy through reducing oxidative stress in
      SLE.

PMID- 24673155
TI  - The development of new basal insulins: is there any clinical advantage with their
      use in type 2 diabetes?
AB  - INTRODUCTION: The basal insulin products currently on market do not optimally
      mimic endogenous insulin secretion. These unmet clinical needs have fueled the
      development of new basal insulin analogues for improving their
      pharmacokinetics/pharmacodynamics profile. AREAS COVERED: We review the recent
      literature investigating the efficacy and safety of new basal insulin analogues
      in type 2 diabetes, as in the USA, insulin utilization accounted for 26% of
      treatment visits for these patients in 2012. Insulin degludec is a desB30 insulin
      acylated at the LysB29 residue with a glutamate linker and 16-carbon fatty diacyl
      side chain. Insulin lispro has been PEGylated at lysine B28, via a urethane bond,
      which increases the hydrodynamic size of the molecule and reduces its absorption
      and clearance following subcutaneous administration. Glargine U300 represents a
      new high-strength glargine formulation (300 U/ml): once injected, U300 forms a
      compact subcutaneous depot with a smaller surface area to produce a more gradual
      and prolonged release. Both PEG-lispro and glargine U300 are not yet on the
      market. EXPERT OPINION: Ultra-long acting and high-strength formulations of new
      basal analogues have the potential for less glycemic variability, less
      (nocturnal) hypoglycemia and weight-loss advantage for PEG-lispro. However, these
      new basal insulin analogues need to be monitored closely for adverse signals.

PMID- 24673156
TI  - Prediction of spontaneous bacterial peritonitis in cirrhotic ascites by a simple
      scoring system.
AB  - BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) is a life
      threatening complication in patients with liver cirrhosis. The aim of this
      prospective study was to identify predictors of SBP in order to develop a
      noninvasive method to identify or exclude an episode of SBP. PATIENTS AND
      METHODS: Three hundred and ninety-two consecutive patients, who underwent
      paracentesis from March 2008 through January 2012 in our department due to
      cirrhotic ascites, were screened. Ninety-six patients were excluded, mostly due
      to prior application of antibiotics. SBP was defined by an absolute neutrophil
      count>=250 cells/uL ascites. We evaluated various clinical and laboratory
      parameters as potential predictors of SBP. A scoring system was developed in a
      training set of 220 and validated in a second set of 76 patients. RESULTS: Fifty
      eight patients (26%) in the training set and 17 patients in the validation set
      (22%) suffered from SBP. Thrombocytopenia<=100,000 cells/uL, age>60 years and
      CRP>60 mg/L were identified as independent predictors of SBP. A scoring system
      combining these three parameters (weighting thrombocytopenia and age with 1 point
      each, but CRP with 2 points) reaches a positive predictive value for the
      diagnosis of SBP of 81.8% with a specificity of 98.8% (score>=3). The negative
      predictive value at a threshold of 1 point is 93.5% with a sensitivity of 87.9%.
      Notably, a high MELD score is not associated with SBP (p=0.3344). CONCLUSIONS:
      Combination of age, CRP and platelet count in a simple scoring system helps in
      the rapid diagnosis or exclusion of SBP.

PMID- 24673157
TI  - Exposure of the thorax to a sublethal blast wave causes a hydrodynamic pulse that
      leads to perivenular inflammation in the brain.
AB  - Traumatic brain injury (TBI) caused by an explosive blast (blast-TBI) is
      postulated to result, in part, from transvascular transmission to the brain of a
      hydrodynamic pulse (a.k.a., volumetric blood surge, ballistic pressure wave,
      hydrostatic shock, or hydraulic shock) induced in major intrathoracic blood
      vessels. This mechanism of blast-TBI has not been demonstrated directly. We
      tested the hypothesis that a blast wave impacting the thorax would induce a
      hydrodynamic pulse that would cause pathological changes in the brain. We
      constructed a Thorax-Only Blast Injury Apparatus (TOBIA) and a Jugular-Only Blast
      Injury Apparatus (JOBIA). TOBIA delivered a collimated blast wave to the right
      lateral thorax of a rat, precluding direct impact on the cranium. JOBIA delivered
      a blast wave to the fluid-filled port of an extracorporeal intravenous infusion
      device whose catheter was inserted retrograde into the jugular vein, precluding
      lung injury. Long Evans rats were subjected to sublethal injury by TOBIA or
      JOBIA. Blast injury induced by TOBIA was characterized by apnea and diffuse
      bilateral hemorrhagic injury to the lungs associated with a transient reduction
      in pulse oximetry signals. Immunolabeling 24 h after injury by TOBIA showed up
      regulation of tumor necrosis factor alpha, ED-1, sulfonylurea receptor 1 (Sur1),
      and glial fibrillary acidic protein in veins or perivenular tissues and
      microvessels throughout the brain. The perivenular inflammatory effects induced
      by TOBIA were prevented by ligating the jugular vein and were reproduced using
      JOBIA. We conclude that blast injury to the thorax leads to perivenular
      inflammation, Sur1 up-regulation, and reactive astrocytosis resulting from the
      induction of a hydrodynamic pulse in the vasculature.

PMID- 24673158
TI  - Risk assessment of transfusion-associated babesiosis in Tyrol: appraisal by
      seroepidemiology and polymerase chain reaction.
AB  - BACKGROUND: After malaria, babesiosis is the second most common transfusion
      transmitted parasitic disease in the United States. In Europe, one reported
      transfusion case, concerning Babesia microti, occurred in Germany. STUDY DESIGN
      AND METHODS: Due to the fact that Babesia spp. are present in Tyrolean ticks, the
      aim of this study is to assess the occurrence of immunoglobulin (Ig)G antibodies
      against the Babesia divergens complex, including B. divergens and Babesia
      venatorum (EU1), as well as B. microti by screening a representative collective
      of 988 blood donors from North and East Tyrol (Austria) with indirect
      immunofluorescence antibody test. Additionally, we investigated 206 local ixodid
      ticks for the presence of babesial DNA by polymerase chain reaction. RESULTS:
      Seroprevalence data resulted in rates of 2.1% for IgG antibodies against the B.
      divergens complex and 0.6% against B. microti in Tyrolean blood donors. All sera
      could be confirmed by independent retesting. Our data indicate that cross
      reactivity is high between B. divergens and B. venatorum and lower than 19.8%
      between B. divergens and B. microti. CONCLUSIONS: This study shows that Babesia
      spp. are present in the Tyrols, which blood donors come into serologic contact
      with, and that we have to consider how to sustain blood product safety concerning
      this new challenge. Additionally, it is the first description of B. venatorum in
      the Tyrols, found in one Ixodes ricinus at the Italian border.

PMID- 24673160
TI  - The influence of surface on the running velocities of elite and amateur orienteer
      athletes.
AB  - We compared the reduction in running velocities from road to off-road terrain in
      eight elite and eight amateur male orienteer athletes to investigate whether this
      factor differentiates elite from amateur athletes. On two separate days, each
      subject ran three 2-km time trials and three 20-m sprints "all-out" on a road, on
      a path, and in a forest. On a third day, the running economy and maximal aerobic
      power of individuals were assessed on a treadmill. The elite orienteer ran faster
      than the amateur on all three surfaces and at both distances, in line with their
      better running economy and aerobic power. In the forest, the elites ran at a
      slightly higher percentage of their 2-km (~3%) and 20-m (~4%) road velocities.
      Although these differences did not exhibit traditional statistical significance,
      magnitude-based inferences suggested likely meaningful differences, particularly
      during 20-m sprinting. Of course, cognitive, mental, and physical attributes
      other than the ability to run on different surfaces are required for excellence
      in orienteering (e.g., a high aerobic power). However, we suggest that athlete
      specific assessment of running performance on various surfaces and distances
      might assist in tailoring training and identifying individual strengths and/or
      weaknesses in an orienteer. 

PMID- 24673159
TI  - The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase
      A2 via GPR120 receptor to produce prostaglandin E2 and plays an anti-inflammatory
      role in macrophages.
AB  - Docosahexaenoic acid (DHA) is one of the major ingredients of fish oil and has
      been reported to have anti-inflammatory properties mediated through the GPR120
      receptor. Whether cytosolic phospholipase A2 (cPLA2 ) and lipid mediators
      produced from cPLA2 activation are involved in the anti-inflammatory role of DHA
      in macrophages has not been reported. We report here that DHA and the GPR120
      agonist, GW9508, activate cPLA2 and cyclooxygenase 2 (COX-2), and cause
      prostaglandin E2 (PGE2) release in a murine macrophage cell line RAW264.7 and in
      human primary monocyte-derived macrophages. DHA and GW9508 activate cPLA2 via
      GPR120 receptor, G protein Galphaq and scaffold protein beta-arrestin 2.
      Extracellular signal-regulated kinase 1/2 activation is involved in DHA- and
      GW9508-induced cPLA2 activation, but not p38 mitogen-activated protein kinase.
      The anti-inflammatory role of DHA and GW9508 is in part via activation of cPLA2 ,
      COX-2 and production of PGE2 as a cPLA2 inhibitor or a COX-2 inhibitor partially
      reverses the DHA- and GW9508-induced inhibition of lipopolysaccharide-induced
      interleukin-6 secretion. The cPLA2 product arachidonic acid and PGE2 also play an
      anti-inflammatory role. This effect of PGE2 is partially through inhibition of
      the nuclear factor-kappaB signalling pathway and through the EP4 receptor of PGE2
      because an EP4 inhibitor or knock-down of EP4 partially reverses DHA inhibition
      of lipopolysaccharide-induced interleukin-6 secretion. Hence, DHA has an anti
      inflammatory effect partially through induction of PGE2.

PMID- 24673161
TI  - Otolith microchemistry of tropical diadromous fishes: spatial and migratory
      dynamics.
AB  - Otolith microchemistry was applied to quantify migratory variation and the
      proportion of native Caribbean stream fishes that undergo full or partial marine
      migration. Strontium and barium water chemistry in four Puerto Rico, U.S.A.,
      rivers was clearly related to a salinity gradient; however, variation in water
      barium, and thus fish otoliths, was also dependent on river basin. Strontium was
      the most accurate index of longitudinal migration in tropical diadromous fish
      otoliths. Among the four species examined, bigmouth sleeper Gobiomorus dormitor,
      mountain mullet Agonostomus monticola, sirajo goby Sicydium spp. and river goby
      Awaous banana, most individuals were fully amphidromous, but 9-12% were semi
      amphidromous as recruits, having never experienced marine or estuarine conditions
      in early life stages and showing no evidence of marine elemental signatures in
      their otolith core. Populations of one species, G. dormitor, may have contained a
      small contingent of semi-amphidromous adults, migratory individuals that
      periodically occupied marine or estuarine habitats (4%); however, adult migratory
      elemental signatures may have been confounded with those related to diet and
      physiology. These findings indicate the plasticity of migratory strategies of
      tropical diadromous fishes, which may be more variable than simple categorization
      might suggest. 

PMID- 24673162
TI  - Perceived discrimination among African American adolescents and allostatic load:
      a longitudinal analysis with buffering effects.
AB  - This study was designed to examine the prospective relations of perceived racial
      discrimination with allostatic load (AL), along with a possible buffer of the
      association. A sample of 331 African Americans in the rural South provided
      assessments of perceived discrimination from ages 16 to 18 years. When youth were
      18 years, caregivers reported parental emotional support and youth assessed peer
      emotional support. AL and potential confounder variables were assessed when youth
      were 20. Latent growth mixture modeling identified two perceived discrimination
      classes: high and stable, and low and increasing. Adolescents in the high and
      stable class evinced heightened AL even with confounder variables controlled. The
      racial discrimination to AL link was not significant for young adults who
      received high emotional support.

PMID- 24673163
TI  - Bis-alkylamine Indolo[3,2-b]quinolines as hemozoin ligands: implications for
      antimalarial cytostatic and cytocidal activities.
AB  - To get insight into the relevance of targeting hemozoin (Hz) crystals, two
      isomeric series, N5,N10-bis-alkylamine (2a-k) and N10,O11-bis-alkylamine (3a-k)
      indolo[3,2-b]quinolines, were evaluated for their in vitro activity against
      chloroquine (CQ)-resistant and sensitive strains of Plasmodium falciparum. In
      general, compounds of series 3 were more active than isomers 2, with IC50/LD50
      ranging from 25/233 nM (3i) to 1.3 (3a)/10.7 (3b) MUM. SAR analyses showed that
      lipophilicity and chlorine substitution at C3 increased both cytostatic and
      cytocidal activities. Both series bound to hematin monomer, inhibited beta
      hematin formation in vitro, delayed intraerythrocytic parasite development with
      apparent inhibition of Hz biocrystallization, and showed higher cytocidal
      activity against schizonts. In addition, cytostatic and cytocidal activities of
      series 3, but not those of isomers 2, correlated with calculated vacuole
      accumulation ratios, suggesting different capacities of 2 and 3 to bind to the Hz
      crystal face {001} exposed on the vacuole aqueous medium and different mechanisms
      of cytocidal potency. 

PMID- 24673164
TI  - A phase-field approach for wetting phenomena of multiphase droplets on solid
      surfaces.
AB  - We study the equilibrium wetting behavior of immiscible multiphase systems on a
      flat, solid substrate. We present numerical computations which are based on a
      vector-valued multiphase-field model of Allen-Cahn type, with a new boundary
      condition, based on appropriately designed surface energy contributions in order
      to ensure the right contact angles at multiphase junctions. Experimental
      investigations are carried out to validate the method and to support the
      numerical results. 

PMID- 24673165
TI  - Oral zinc supplements are ineffective for treating acute dehydrating diarrhoea in
      5-12-year-olds.
AB  - AIM: Many countries have guidelines recommending the use of oral zinc in acute
      dehydrating diarrhoea in children aged 2 months to 5 years of age, but no
      guidelines exist for older children. This study tested how effective existing
      recommendations are in children from 5 to 12 years of age. METHODS: Children
      hospitalised with acute dehydrating diarrhoea (n = 134) were randomised to
      receive 40 mg of oral zinc sulphate tablets or a placebo for 14 days. The primary
      outcome variable was the time taken for diarrhoea to stop. Secondary outcome
      variables included time taken for rehydration, duration of hospitalisation and
      recurrence of diarrhoea in the next 3 months. RESULTS: The median time for
      resolution of diarrhoea was 60 h in both groups. The zinc group was marginally
      better, but not statistically significant, for resolution (hazard ratio = 0.89,
      95% CI 0.63-1.24), rehydration (hazard ratio = 0.93, 95% CI 0.66-1.32) and
      hospitalisation (hazard ratio = 0.94, 95% CI 0.67-1.34). The risk ratio of
      recurrence for zinc versus placebo (95% CI) was 0.65 [0.37-1.23] [p = 0.11].
      CONCLUSION: Daily zinc supplements (40 mg for 14 days) in children aged 5-12
      years with acute dehydrating diarrhoea did not shorten the duration of diarrhoea
      or reduce subsequent episodes. Further adequately sized, community-based trials
      are needed.

PMID- 24673166
TI  - Effects of integrated child development and nutrition interventions on child
      development and nutritional status.
AB  - We conducted a systematic review of studies that examined the effect of
      interventions combining a child development component with a nutrition one; in
      some cases the nutrition interventions also included health-promotion components.
      Only papers with both child development and nutrition outcomes and rated as
      moderate-to-good quality were included. Eleven efficacy and two nonrandomized
      trials, and eight program evaluations were identified. Only six trials examined
      interventions separately and combined. The trials showed nutritional
      interventions usually benefited nutritional status and sometimes benefited child
      development. Stimulation consistently benefited child development. There was no
      significant loss of any effect when interventions were combined, but there was
      little evidence of synergistic interaction between nutrition and stimulation on
      child development. Only three trials followed up the children after intervention.
      All at-scale program evaluations were combined interventions. Five benefited
      child development, but one did not, and two showed deficits. There was generally
      little benefit of at-scale programs to nutritional status. We found no rigorous
      evaluations of adding stimulation to health and nutrition services at scale and
      there is an urgent need for them. There is also a need to establish quality
      control mechanisms for existing scaled-up programs and to determine their long
      term effects. There is also a need to determine if there are any sustained
      benefits for the children after programs finish. 

PMID- 24673167
TI  - Formative research methods for designing culturally appropriate, integrated child
      nutrition and development interventions: an overview.
AB  - Nutritional and developmental insults in the first few years of life have
      profound public health implications, including substantial contributions to
      neonatal, infant, and early childhood morbidity and mortality, as well as longer
      term effects on cognitive development, school achievement, and worker
      productivity. Optimal development that can lead to the attainment of an
      individual's fullest potential, therefore, requires a combination of genetic
      capacity, adequate nutrition, psychosocial stimulation, and safe, clean physical
      environments. Researchers and policymakers have called for integrated child
      nutrition and development interventions for more than 20 years, yet there are
      only a handful of efficacy trials and even fewer examples of integrated
      interventions that have been taken to scale. While a critical component in the
      design of such interventions is formative research, there is a dearth of
      information in both the literature and policy arenas to guide this phase of the
      process. To move the field forward, this paper first provides an overview of
      formative research methods with a focus on qualitative inquiry, a description of
      the critical domains to be assessed (infant and young child feeding, responsive
      feeding, and child development), and currently available resources. Application
      of these methods is provided through a real-world case study--the design of an
      integrated nutrition and child development efficacy trial in Andhra Pradesh,
      India. Recommendations for next steps are discussed, the most important of which
      is the need for a comprehensive set of formative guidelines for designing locally
      tailored, culturally appropriate, integrated interventions.

PMID- 24673168
TI  - Integrating nutrition and early child-development interventions among infants and
      preschoolers in rural India.
AB  - This article describes the development, design, and implementation of an
      integrated randomized double-masked placebo-controlled trial (Project Grow Smart)
      that examines how home/preschool fortification with multiple micronutrient powder
      (MNP) combined with an early child-development intervention affects child
      development, growth, and micronutrient status among infants and preschoolers in
      rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months)
      and a preschool phase (enrollment age: 36-48 months). Infants are individually
      randomized into one of four groups: placebo, placebo plus early learning, MNP
      alone, and MNP plus early learning (integrated intervention), conducted through
      home visits. The preschool phase is a cluster-randomized trial conducted in
      Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated
      Child Development System of India. AWCs are randomized into MNP or placebo, with
      the MNP or placebo mixed into the children's food. The evaluation examines
      whether the effects of the MNP intervention vary by the quality of the early
      learning opportunities and communication within the AWCs. Study outcomes include
      child development, growth, and micronutrient status. Lessons learned during the
      development, design, and implementation of the integrated trial can be used to
      guide large-scale policy and programs designed to promote the developmental,
      educational, and economic potential of children in developing countries. 

PMID- 24673170
TI  - Does alcohol consumption increase the risk of cutaneous melanoma? Comments on a
      recent meta-analysis: reply from the authors.

PMID- 24673169
TI  - Does influenza A infection increase oxidative damage?
AB  - Considerable data implicate oxidative damage in influenza pathogenesis. We
      examined temporal changes in oxidative damage using accurate biomarkers in an
      adult cohort with acute influenza infection and their relationships with clinical
      parameters. Clinical information and blood samples were collected during their
      acute illness and 3 months later. A fatigue questionnaire was administered 3
      months following influenza infection. Thirty-five patients (mean age, 34 years)
      with polymerase chain reaction-confirmed influenza A infection were included; all
      patients returned for follow-up assessments. Adjusted levels of plasma F2
      isoprostanes, total hydroxyeicosatetraenoic products (HETEs), 7beta
      hydroxycholesterol and 7-ketocholesterol, serum gamma-glutamyltransferase, and
      high-sensitivity C-reactive protein (hsCRP) were increased during the acute
      illness compared with age-matched controls. Despite clinical recovery, levels of
      these biomarkers remained higher at month 3 compared with controls. A proportion
      of patients had persistent symptoms such as fatigue (23%), myalgia (14%), and
      arthralgia (11%) at month 3. Patients with significant fatigue had higher
      baseline levels of plasma F2-isoprostanes, F4-neuroprostanes, and total HETEs
      compared to those without fatigue. By contrast, patients with persistent
      arthralgia and myalgia had higher baseline levels of serum hsCRP compared to
      those without these symptoms. Our observations lead to the hypothesis that
      oxidative damage participates in the pathogenesis of influenza infection and
      postinfectious fatigue.

PMID- 24673171
TI  - mHealth adoption in low-resource environments: a review of the use of mobile
      healthcare in developing countries.
AB  - The acknowledged potential of using mobile phones for improving healthcare in low
      resource environments of developing countries has yet to translate into
      significant mHealth policy investment. The low uptake of mHealth in policy
      agendas may stem from a lack of evidence of the scalable, sustainable impact on
      health indicators. The mHealth literature in low- and middle-income countries
      reveals a burgeoning body of knowledge; yet, existing reviews suggest that the
      projects yield mixed results. This article adopts a stage-based approach to
      understand the varied contributions to mHealth research. The heuristic of inputs
      mechanism-outputs is proposed as a tool to categorize mHealth studies. This
      review (63 articles comprising 53 studies) reveals that mHealth studies in
      developing countries tend to concentrate on specific stages, principally on pilot
      projects that adopt a deterministic approach to technological inputs (n = 32),
      namely introduction and implementation. Somewhat less studied were research
      designs that demonstrate evidence of outputs (n = 15), such as improvements in
      healthcare processes and public health indicators. The review finds a lack of
      emphasis on studies that provide theoretical understanding (n = 6) of adoption
      and appropriation of technological introduction that produces measurable health
      outcomes. As a result, there is a lack of dominant theory, or measures of outputs
      relevant to making policy decisions. Future work needs to aim for establishing
      theoretical and measurement standards, particularly from social scientific
      perspectives, in collaboration with researchers from the domains of information
      technology and public health. Priorities should be set for investments and
      guidance in evaluation disseminated by the scientific community to practitioners
      and policymakers.

PMID- 24673172
TI  - Spectroscopy of nitrophenolates in vacuo: effect of spacer, configuration, and
      microsolvation on the charge-transfer excitation energy.
AB  - In a charge-transfer (CT) transition, electron density moves from one end of the
      molecule (donor) to the other end (acceptor). This type of transition is of
      paramount importance in nature, for example, in photosynthesis, and it governs
      the excitation of several protein biochromophores and luminophores such as the
      oxyluciferin anion that accounts for light emission from fireflies. Both
      transition energy and oscillator strength are linked to the coupling between the
      donor and acceptor groups: The weaker the coupling, the smaller the excitation
      energy. But a weak coupling necessarily also causes a low oscillator strength
      possibly preventing direct excitation (basically zero probability in the
      noncoupling case). The coupling is determined by the actual spacer between the
      two groups, and whether the spacer acts as an insulator or a conductor. However,
      it can be difficult or even impossible to distinguish the effect of the spacer
      from that of local solvent molecules that often cause large solvent shifts due to
      different ground-state and excited-state stabilization. This calls for gas-phase
      spectroscopy experiments where absorption by the isolated molecule is identified
      to unequivocally establish the intrinsic molecular properties with no
      perturbations from a microenvironment. From such insight, the effect of a protein
      microenvironment on the CT excited state can be deduced. In this Account, we
      review our results over the last 5 years from mass spectroscopy experiments using
      specially designed apparatus on several charged donor-acceptor ions that are
      based on the nitrophenolate moiety and pi-extended derivatives, which are
      textbook examples of donor-acceptor chromophores. The phenolate oxygen is the
      donor, and the nitro group is the acceptor. The choice of this system is also
      based on the fact that phenolate is a common structural motif of biochromophores
      and luminophores, for example, it is a constituent of the oxyluciferin anion. A
      presentation of the setups used for gas-phase ion spectroscopy in Aarhus is
      given, and we address issues of whether double bonds or triple bonds best convey
      electronic coupling between the phenolate oxygen and the nitro group, the
      significance of separating the donor and acceptor spatially, the influence of
      cross-conjugation versus linear conjugation, and along this line ortho versus
      meta versus para configuration, and not least the effect of a single solvent
      molecule (water, methanol, or acetonitrile). From systematic studies, a clear
      picture has emerged that has been supported by high-level calculations of
      electronically excited states. Our work shows that CC2 coupled-cluster
      calculations of vertical excitation energies are within 0.2 eV of experimental
      band maxima, and importantly, that the theoretical method is excellent in
      predicting the relative order of excitation energies of a series of
      nitrophenolates. Finally, we discuss future challenges such as following the
      change in absorption as a function of the number of solvent molecules and when
      gradually approaching the bulk limit.

PMID- 24673173
TI  - Genetic variation of the whole ICAM4 gene in Caucasians and African Americans.
AB  - BACKGROUND: Landsteiner-Wiener (LW) is the human blood group system Number 16,
      which comprises two antithetical antigens, LW(a) and LW(b) and the high
      prevalence antigen LW(ab) . LW is encoded by the intracellular adhesion molecule
      4 (ICAM4) gene. The ICAM4 protein is part of the Rhesus complex in the red cell
      membrane and is involved in cell-cell adhesion. STUDY DESIGN AND METHODS: We
      developed a method to sequence the whole 1.9-kb ICAM4 gene from genomic DNA in
      one amplicon. We determined the nucleotide sequence of Exons 1 to 3, the two
      introns, and 402-bp 5'-untranslated region (UTR) and 347-bp 3'-UTR in 97
      Caucasian and 91 African American individuals. RESULTS: Seven variant ICAM4
      alleles were found, distinct from the wild-type ICAM4 allele (GenBank KF712272),
      known as LW*05 and encoding LW(a) . An effect of the LW(a) /LW(b) amino acid
      substitution on the protein structure was predicted by two of the three
      computational modeling programs used. CONCLUSIONS: We describe a practical
      approach for sequencing and determining the ICAM4 alleles using genomic DNA.
      LW*05 is the ancestral allele, which had also been observed in a Neanderthal
      sample. All seven variant alleles are immediate derivatives of the prevalent
      LW*05 and caused by one single-nucleotide polymorphism (SNP) in each allele. Our
      data were consistent with the NHLBI GO Exome Sequencing Project (ESP) and the
      dbSNP databases, as all SNPs had been observed previously. Our study has the
      advantage over the other databases in that it adds haplotype (allele) information
      for the ICAM4 gene, clinically relevant in the field of transfusion medicine.

PMID- 24673174
TI  - JAK/STAT pathway in Drosophila immunity.
AB  - The Janus kinase/signal transducer and activator of transcription (JAK/STAT)
      signalling pathway controls multiple biological processes in metazoan development
      and tissue homoeostasis. This creates a need for tight regulatory mechanisms to
      ensure proper responses. The core components of the pathway, as well as many of
      the regulatory molecules, are conserved in evolution and thus share similarities
      in organisms such as humans and fruit flies. Therefore, the fruit fly provides an
      amenable model system for elucidating the in vivo roles of the JAK/STAT pathway
      and its regulators, which are challenging to demonstrate in mammalian systems.
      This review will focus on describing recent advances in understanding the
      importance of JAK/STAT signalling in Drosophila immunity.

PMID- 24673175
TI  - An update on new adoptive immunotherapy strategies for solid tumors with cytokine
      induced killer cells.
AB  - INTRODUCTION: Cytokine-induced killer (CIK) cells are mainly CD3(+)CD56(+) NKT
      cells exhibiting non-MHC-restricted cytotoxicity against a broad range of tumors.
      Much research is going on to improve CIK cell effectivity and to evaluate the
      clinical benefit of different combinations with conventional therapies. AREAS
      COVERED: This review provides an update on in vitro/in vivo studies and clinical
      trials applying CIK cells for the treatment of solid tumors. This comprises
      attempts using additional cytokines, genetic engineering and combinations with
      different conventional and modern therapies. EXPERT OPINION: Since our last
      review, much effort has been made to improve CIK cell cytotoxicity and clinical
      effectivity. Targeted CIK cell therapy and combinations of CIK cells with
      antiangiogenic drugs or oncolytic viruses are examples of recent outstanding
      achievements in the field of adoptive CIK cell therapy. The clinical application
      of CIK cells in combination with conventional therapies, especially, obtained
      promising results. However, the best combination and the optimal therapy schedule
      have yet to be defined.

PMID- 24673176
TI  - Characterization of exopolymeric substances (EPS) produced by Aeromonas
      hydrophila under reducing conditions.
AB  - The aim of this work was to investigate the production of extracellular polymeric
      substances (EPS) by Aeromonas hydrophila grown under anaerobic conditions. EPS
      composition was studied for planktonic cells, cells attached to carbon fibre
      supports using a soluble ferric iron source and cells grown with a solid ferric
      iron mineral (gossan). Conventional spectrophotometric methods, Fourier transform
      infrared (FTIR) and confocal laser scanning microscopy (CLSM) were used to
      determine the main components in the biofilm extracted from the cultures. The key
      EPS components were proteins, indicating their importance for electron transfer
      reactions. Carbohydrates were observed mostly on the mineral and contained
      terminal mannosyl and/or terminal glucose, fucose and N-acetylgalactosamine
      residues.

PMID- 24673177
TI  - Carbon nanotube-loaded Nafion film electrochemical sensor for metal ions:
      europium.
AB  - A Nafion film loaded with novel catalyst-free multiwalled carbon nanotubes
      (MWCNTs) was used to modify a glassy carbon (GC) electrode to detect trace
      concentrations of metal ions, with europium ion (Eu(3+)) as a model. The
      interaction between the sidewalls of MWCNTs and the hydrophobic backbone of
      Nafion allows the MWCNTs to be dispersed in Nafion, which was then coated as a
      thin film on the GC electrode surface. The electrochemical response to Eu(3+) was
      found to be ~10 times improved by MWCNT concentrations between 0.5 and 2 mg/mL,
      which effectively expanded the electrode surface into the Nafion film and thereby
      reduced the diffusion distance of Eu(3+) to the electrode surface. At low MWCNT
      concentrations of 0.25 and 0.5 mg/mL, no significant improvement in signal was
      obtained compared with Nafion alone. Scanning electron microscopy and
      electrochemical impedance spectroscopy were used to characterize the structure of
      the MWCNT-Nafion film, followed by electrochemical characterization with Eu(3+)
      via cyclic voltammetry and preconcentration voltammetry. Under the optimized
      conditions, a linear range of 1-100 nM with a calculated detection limit of 0.37
      nM (signal/noise = 3) was obtained for determination of Eu(3+) by Osteryoung
      square-wave voltammetry after a preconcentration time of 480 s. 

PMID- 24673178
TI  - T helper cell cytokine profiles after endurance exercise.
AB  - Endurance exercise can cause immunosuppression and increase the risk of upper
      respiratory illness. The present study examined changes in the secretion of T
      helper (Th) cell cytokines after endurance exercise. Ten highly trained road
      cyclists [mean+/-SEM: age 24.2+/-1.7 years; height 1.82+/-0.02 m; body mass
      73.8+/-2.0 kg; peak oxygen uptake 65.9+/-2.3 mL/(kg*min)] performed 2 h of
      cycling exercise at 90% of the second ventilatory threshold. Peripheral blood
      mononuclear cells were isolated and stimulated with phytohemagglutinin. Plasma
      cortisol concentrations and the concentration of Th1/Th2/Th17 cell cytokines were
      examined. Data were analyzed using both traditional statistics and magnitude
      based inferences. Results revealed a significant decrease in plasma cortisol at 4
      24 h postexercise compared with pre-exercise values. Qualitative analysis
      revealed postexercise changes in concentrations of plasma cortisol, IL-2, TNF, IL
      4, IL-6, IL-10, and IL-17A compared with pre-exercise values. A Th1/Th2 shift was
      evident immediately postexercise. Furthermore, for multiple cytokines, including
      IL-2 and TNF (Th1), IL-6 and IL-10 (Th2), and IL-17 (Th17), no meaningful change
      in concentration occurred until more than 4 h postexercise, highlighting the
      duration of exercise-induced changes in immune function. These results
      demonstrate the importance of considering "clinically" significant versus
      statistically significant changes in immune cell function after exercise.

PMID- 24673179
TI  - Genetic endowment of proinflammatory cytokine tumor necrosis factor-alpha (-) 308
      G > A polymorphism to Parthenium hysterophorus-induced airborne contact
      dermatitis in an Indian cohort.
AB  - BACKGROUND: Parthenium dermatitis is a common airborne allergic health problem
      that induces a cell-mediated hypersensitivity immune response involving activated
      T lymphocytes, which culminates in injury to the skin. The disease is manifested
      as itchy erythematous papules and plaques and primarily affects the exposed areas
      and flexures. This study aimed to identify the role of tumor necrosis factor
      (TNF)-alpha (-) 308 G>A polymorphism in the pathogenesis of parthenium
      dermatitis. MATERIALS AND METHODS: A total of 120 subjects, including 60 patients
      exclusively diagnosed for parthenium dermatitis and 60 healthy individuals, were
      included in the study. The genotyping of the TNF-alpha (-) 308 G>A region was
      carried out by the amplification refractory mutational system. RESULTS: In the
      present study, we demonstrated that polymorphism of the TNF-alpha (-) 308
      position (A and/or G) was not statistically significant, and there was no
      difference in the distribution of any alleles of this locus in cases and
      controls. CONCLUSION: The present study suggests that there is a lack of
      association of potent proinflammatory cytokine TNF-alpha (-) 308 G>A polymorphism
      in parthenium dermatitis in the Indian cohort. It interprets genetically endowed
      transcriptional capacity due to this particular single nucleotide polymorphism
      but does not support the prevalence of high serum levels of TNF-alpha in
      parthenium-induced skin allergic inflammation.

PMID- 24673181
TI  - Collusive induction in perverse relating: perverse enactments and bastions as a
      camouflage for death anxiety.
AB  - The author argues that one of the main functions of perverse relatedness is to
      induce the analyst into becoming the patient's unconscious accomplice in a
      "perverse pact" against the analytic work aimed at disavowing intolerable aspects
      of reality. The intense power of collusive induction in perverse relating leads
      the analyst to participate in transference-countertransference enactments and to
      the crystallization of a silent and chronic unconscious collusion between the
      patient and analyst in the analytic field, stagnating the process (bastion;
      Baranger and Baranger). The author claims that analysis of perverse pathology
      should not be limited to interpretation of the patient's intrapsychic functioning
      but should also focus on the information obtained by the analyst through his
      participation in collusive enactments; the analyst should also take a "second
      look" at the analytic "field" to detect underlying bastions. The author reviews
      the main psychoanalytic contributions that have clarified the phenomenon of
      collusive induction in perverse relating and as an illustration, describes the
      analysis of a man with a perverse character; in this patient, one of the main
      functions of his perverse relatedness was to induce the analyst to become an
      accomplice in his disavowal of his terror of death. The author highlights the
      influence of death anxiety in the bastions that develop in the treatment of
      perverse patients. 

PMID- 24673180
TI  - Children's attractiveness, gender, and race biases: a comparison of their
      strength and generality.
AB  - Although research suggests that facial attractiveness biases significantly affect
      social development and interactions, these biases are understudied in the
      developmental literature and are overlooked when designing interventions relative
      to gender and race. The authors, therefore, compared how much bias 3- to 11-year
      olds (N = 102) displayed in the three domains. They also examined whether bias
      and flexibility (understanding that different social groups can possess similar
      attributes) were related across domains. Children's attractiveness biases,
      particularly for girl targets, were as strong as or stronger than gender or race
      biases. Flexibility, but not bias, was related across domains. Developmental
      scientists and policy makers should increase efforts toward understanding
      development of attractiveness biases and determine which methods of teaching
      flexibility are most successful at reducing bias across domains. 

PMID- 24673182
TI  - The discovery of epidermal tight junctions.
AB  - It was previously thought that the skin barrier is composed singly by the stratum
      corneum. However, this concept was overturned by the report of Tsukita's group in
      2002. They convinced us that tight junctions exist in the stratum granulosum of
      the epidermis, with the constituent proteins being occludin, claudin-1 and
      claudin-4. However, more than 30 years before this, Hashimoto et al. described
      the possible existence of tight junctions in the epidermis in 'Intercellular
      spaces of the human epidermis as demonstrated with lanthanum' in 1971. Dr.
      Hashimoto observed lanthanum nitrate-injected human skin by electron microscopy.
      He discovered that the injected lanthanum penetrated the intercellular spaces of
      the basal and spinous layers of the epidermis and then moved towards the skin
      surface until penetration was halted in the granular cell layer near the stratum
      corneum. He described the cell-to-cell adhesion structures that blocked the
      movement of lanthanum as 'truly tight junctions'. Thus, this was the first
      description of the existence of tight junctions in the epidermis. However, the
      presence of these structures was denied by others and was forgotten. Thanks to
      the discovery of claudin, the existence of tight junctions between epidermal
      keratinocytes was finally confirmed. It is interesting that Hashimoto's finding
      was eventually proved to be correct three decades later as a result of progress
      in molecular biology. This article encourages us to recognize the importance of
      careful observation in the molecular biology era.

PMID- 24673183
TI  - Effect of carbon dioxide on cerebral blood flow velocity in preterm infants
      during postnatal transition.
AB  - AIM: High arterial carbon dioxide (PaCO2 ) and cerebral reperfusion are
      associated with peri/intraventricular haemorrhage. Our aim was to study the
      relationship between PaCO2 and cerebral blood flow (CBF) in preterm infants
      during postnatal transition. METHODS: We prospectively studied <=30 weeks'
      gestation haemodynamically stable preterm infants during the first three
      postnatal days (n = 21; gestational age 25.8 +/- 1.4 weeks). We measured middle
      cerebral artery mean flow velocity (MCA-MV) as a surrogate for CBF at the time of
      blood gas analysis. RESULTS: We obtained 78 PaCO2 -MCA-MV data pairs. The
      expected positive linear relationship between PaCO2 and MCA-MV was absent on the
      first postnatal day, equivocal on the second and present on the third. Using
      piecewise bilinear regression models, we identified PaCO2 breakpoints at 52.7 and
      51.0 mmHg for postnatal days two and three, respectively. CONCLUSION: In
      haemodynamically stable preterm neonates, the expected positive linear
      relationship between PaCO2 and CBF may be absent on postnatal day one. On
      postnatal day three, and possibly day two, a PaCO2 threshold exists for this
      relationship, above which CBF becomes reactive to PaCO2 . We speculate that the
      enhanced CBF response to PaCO2 above the threshold contributes to the reperfusion
      injury and partly explains the association between hypercapnia and
      peri/intraventricular haemorrhage.

PMID- 24673184
TI  - Implementing two treatment approaches to childhood dysarthria.
AB  - The paucity of evidence and detail in the literature regarding speech treatment
      for children with dysarthria due to cerebral palsy (CP) renders it difficult for
      researchers to replicate studies and make further inroads into this area in need
      of exploration. Furthermore, for speech-language pathologists (SLPs) wishing to
      follow treatments that the literature indicates have promise, little guidance is
      available on the details of the treatments that yielded the positive results. The
      present article details the implementation of two treatment approaches in speech
      treatment research for children with dysarthria: Speech Systems Intelligibility
      Treatment (SSIT) and the Lee Silverman Voice Treatment LOUD (LSVT LOUD). Specific
      strategies, primarily for treatment, but also for outcome measurement and
      acoustic analysis of dysarthric speech, are described. These techniques are
      provided for researchers and clinicians to consider implementing in order to
      advance speech treatment for this population. New data from research using these
      approaches are presented, including findings of acoustic vowel space changes
      following both speech treatments.

PMID- 24673185
TI  - Cantonese tone production performance of mainstream school children with hearing
      impairment.
AB  - This study investigated the Cantonese tone production ability of children with
      hearing impairment studying in mainstream schools. The participants were 87
      Cantonese-speaking children with mild-to-profound degrees of hearing loss aged
      5.92-13.58 in Hong Kong. Most of the children were fitted with hearing aids (n =
      65); 17 of them had profound hearing impairment, one who had severe hearing loss
      had cochlear implantation, and four who had mild hearing loss were without any
      hearing device. The Hong Kong Cantonese Articulation Test was administered, and
      the tones produced were rated by two of the authors and a speech-language
      pathologist. Group effects of tones, hearing loss level, and also an interaction
      of the two were found to be significant. The children with profound hearing
      impairment performed significantly worse than most of the other children. Tone 1
      was produced most accurately, whereas tone 6 productions were the poorest. No
      relationship was found between the number of years of mainstreaming and tone
      production ability. Tone production error pattern revealed that confusion
      patterns in tone perception coincided with those in production. Tones having a
      similar fundamental frequency (F0) at the onset also posed difficulty in tone
      production for children with hearing impairment.

PMID- 24673187
TI  - Marsupellins A-F, ent-longipinane-type sesquiterpenoids from the Chinese
      liverwort Marsupella alpine with acetylcholinesterase inhibitory activity.
AB  - Acetylcholinesterase (AChE) inhibitory activity-guided fractionation of the
      Chinese liverwort Marsupella alpine afforded six new [marsupellins A-F (1-6)] and
      three known (7-9) ent-longipinane-type sesquiterpenoids. The structures were
      determined from MS and NMR spectroscopic data, single-crystal X-ray diffraction,
      and electronic circular dichroism calculations. Compounds 1-9 exhibited moderate
      to weak AChE inhibitory activity. 

PMID- 24673188
TI  - The ambiguity of standing in standing devices: a qualitative interview study
      concerning children and parents experiences of the use of standing devices.
AB  - AIM: The aim of this study was to describe children's and parents' experiences of
      the significance of standing in a standing device. METHODS: Individual interviews
      were performed with six children/teenagers (aged 7-19 years) and 14 parents. The
      interviews were transcribed and analyzed using a qualitative content analysis.
      FINDINGS: The analysis resulted in the major theme, the duality of uprightness
      and the related themes: (1) the instrumental dimension of standing; (2) the
      social dimension of standing; and (3) the ambivalent dimension of standing. Each
      of the themes comprised several subthemes. CONCLUSIONS: There is an inherent
      duality related to the use of a standing device. Standing in a standing device
      was seen as a treatment of body structures and functions, as well as a possible
      source of pain. Standing was considered to influence freedom in activities and
      participation both positively and negatively. The parents experienced that
      standing influenced other peoples' views of their child, while the children
      experienced standing as a way to extend the body and as something that gave them
      benefits in some activities. Physiotherapists working with children should take
      into account both the social and physical dimensions of using a standing device
      and consider both the child's and the parents' views.

PMID- 24673186
TI  - The journey from stem cell to macrophage.
AB  - Essential protectors against infection and injury, macrophages can also
      contribute to many common and fatal diseases. Here, we discuss the mechanisms
      that control different types of macrophage activities in mice. We follow the
      cells' maturational pathways over time and space and elaborate on events that
      influence the type of macrophage eventually settling a particular destination.
      The nature of the precursor cells, developmental niches, tissues, environmental
      cues, and other connecting processes appear to contribute to the identity of
      macrophage type. Together, the spatial and developmental relationships of
      macrophages compose a topo-ontogenic map that can guide our understanding of
      their biology. 

PMID- 24673189
TI  - Influence of electrostatic interactions on the release of charged molecules from
      lipid cubic phases.
AB  - The release of positive, negative, and neutral hydrophilic drugs from pH
      responsive bicontinuous cubic phases was investigated under varying conditions of
      electrostatic interactions. A weak acid, linoleic acid (LA), or a weak base,
      pyridinylmethyl linoleate (PML), were added to the neutral monolinolein (ML) in
      order to form lyotropic liquid-crystalline (LLC) phases, which are negatively
      charged at neutral pH and positively charged at acidic pH. Release studies at low
      ionic strength (I = 20 mM) and at different pH values (3 and 7) revealed that
      electrostatic attraction between a positive drug, proflavine (PF), and the
      negatively charged LLC at pH = 7 or between a negative drug, antraquinone 2
      sulfonic acid sodium salt (AQ2S), and the positively charged LLC at pH = 3 did
      delay the release behavior, while electrostatic repulsion affects the transport
      properties only to some extent. Release profiles of a neutral drug, caffeine,
      were not affected by the surface charge type and density in the cubic LLCs.
      Moreover, the influence of ionic strength was also considered up to 150 mM,
      corresponding to a Debye length smaller than the LLC water channels radius, which
      showed that efficient screening of electrostatic attractions occurring within the
      LLC water domains results in an increased release rate. Four transport models
      were applied to fit the release data, providing an exhaustive, quantitative
      insight on the role of electrostatic interactions in transport properties from pH
      responsive bicontinuous cubic phases. 

PMID- 24673190
TI  - DNA-encoded chemical libraries: advancing beyond conventional small-molecule
      libraries.
AB  - DNA-encoded chemical libraries (DECLs) represent a promising tool in drug
      discovery. DECL technology allows the synthesis and screening of chemical
      libraries of unprecedented size at moderate costs. In analogy to phage-display
      technology, where large antibody libraries are displayed on the surface of
      filamentous phage and are genetically encoded in the phage genome, DECLs feature
      the display of individual small organic chemical moieties on DNA fragments
      serving as amplifiable identification barcodes. The DNA-tag facilitates the
      synthesis and allows the simultaneous screening of very large sets of compounds
      (up to billions of molecules), because the hit compounds can easily be identified
      and quantified by PCR-amplification of the DNA-barcode followed by high
      throughput DNA sequencing. Several approaches have been used to generate DECLs,
      differing both in the methods used for library encoding and for the combinatorial
      assembly of chemical moieties. For example, DECLs can be used for fragment-based
      drug discovery, displaying a single molecule on DNA or two chemical moieties at
      the extremities of complementary DNA strands. DECLs can vary substantially in the
      chemical structures and the library size. While ultralarge libraries containing
      billions of compounds have been reported containing four or more sets of building
      blocks, also smaller libraries have been shown to be efficient for ligand
      discovery. In general, it has been found that the overall library size is a poor
      predictor for library performance and that the number and diversity of the
      building blocks are rather important indicators. Smaller libraries consisting of
      two to three sets of building blocks better fulfill the criteria of drug-likeness
      and often have higher quality. In this Account, we present advances in the DECL
      field from proof-of-principle studies to practical applications for drug
      discovery, both in industry and in academia. DECL technology can yield specific
      binders to a variety of target proteins and is likely to become a standard tool
      for pharmaceutical hit discovery, lead expansion, and Chemical Biology research.
      The introduction of new methodologies for library encoding and for compound
      synthesis in the presence of DNA is an exciting research field and will crucially
      contribute to the performance and the propagation of the technology.

PMID- 24673191
TI  - Coinfusion of dextrose-containing fluids and red blood cells does not adversely
      affect in vitro red blood cell quality.
AB  - BACKGROUND: Transfusion guidelines advise against coinfusing red blood cells
      (RBCs) with solutions other than 0.9% saline. We evaluated the impact of
      coinfusion with dextrose-containing fluids (DW) on markers of RBC quality. STUDY
      DESIGN AND METHODS: A pool-and-split design was used to allow conditions to be
      tested on each pool within 2 hours of irradiation. Three pools at each storage
      age (5, 14, and 21 days) were created for each phase. In Phase 1, samples were
      infused through a neonatal transfusion apparatus alone or with treatment
      solutions: D5W, D10W, D5W/0.2% saline, and 0.9% saline. In Phase 2, samples were
      incubated alone or in a 1:1 ratio with treatment solutions and tested after 5,
      30, and 180 minutes. Hemolysis, supernatant potassium, RBC indices, morphology,
      and deformability were measured on all samples. RESULTS: In Phase 1, RBCs
      transfused alone through the apparatus had higher (p<0.01) hematocrit, total
      hemoglobin, and supernatant potassium compared to all other groups. No
      statistical differences were identified between groups for other measured
      variables. In Phase 2, mean corpuscular volume of all samples containing DW
      increased with incubation length and were higher (p<0.01) than RBCs incubated
      alone or with 0.9% saline after 30 and 180 minutes. RBCs incubated with D5W and
      D5W/0.2% saline had greater (p<0.05) hemolysis than RBCs alone after 180 minutes.
      CONCLUSION: In vitro characteristics of RBCs coinfused with 0.9% saline or D10W
      were not adversely impacted. When developing clinical studies in neonates, we
      recommend use of D10W and a transfusion apparatus that minimizes the contact
      volume of the coinfusate with the RBC.

PMID- 24673192
TI  - Exogenous high-mobility group box 1 inhibits apoptosis and promotes the
      proliferation of lewis cells via RAGE/TLR4-dependent signal pathways.
AB  - Upregulated high-mobility group box 1 (HMGB1) has been found in many diseases.
      Nevertheless, the function of HMGB1 on modulating the proliferation of lung
      cancer cells (Lewis cells) and inhibiting apoptosis is poorly understood, as well
      as the involved intracellular signalling. In the present study, we firstly found
      the apoptosis of Lewis was increased following Hanks' balanced salt solution
      (HBSS)-induced starvation, while it was rescued after exogenous HMGB1 protein was
      added; furthermore, the receptor for advanced glycation end products (RAGE) and
      Toll-like receptor (TLR4) could coordinately improve the proliferation of tumour
      cells in vitro, and HMGB1 could enhance the phosphorylation of PI3K/Akt and
      Erk1/2, inhibit the expression of pro-apoptosis protein Bax and promote the
      expression of anti-apoptosis protein Bcl-2. These findings clearly demonstrated
      that HMGB1-RAGE/TLR4- PI3K-Akt/Erk1/2 pathway contributed to the proliferation of
      Lewis. Moreover, our observations provide experimental and theoretical basis for
      clinical biological therapy for cancers; it also may be a new target for
      intervention and treatment of lung cancer.

PMID- 24673193
TI  - Effect of the FTO rs9930506 polymorphism on obesity and the main clinical
      outcomes in patients with psoriasis.

PMID- 24673194
TI  - Does the number of cancer patients' close social ties affect cancer-related
      information seeking through communication efficacy? Testing a mediation model.
AB  - This study addresses whether having a broad social network of close friends
      equips cancer patients with increased efficacy to engage in communication about
      their cancer, which then leads to an increased likelihood of patients actively
      seeking cancer-related information. Guided by the theory of motivated information
      management, the study also tests whether the effect of the number of close social
      ties on information seeking is mediated, in part, by communication efficacy.
      Results are based on data collected from a randomly drawn sample from the
      Pennsylvania Cancer Registry of 2,013 cancer patients who completed mail surveys
      in the Fall of 2006. Results are consistent with a cross-sectional mediation
      effect in which the number of close social ties in one's social network is
      positively associated with communication efficacy (b = .17, p = .001), which, in
      turn, is positively associated with cancer-related information seeking (b = .13,
      p < .001).

PMID- 24673195
TI  - Synthesis of two-dimensional analogues of copolymers by site-to-site
      transmetalation of organometallic monolayer sheets.
AB  - Monolayer sheets have gained attention due to the unique properties derived from
      their two-dimensional structure. One of the key challenges in sheet
      modification/synthesis is to exchange integral parts while keeping them intact.
      We describe site-to-site transmetalation of Zn(2+) in the netpoints of cm(2)
      sized, metal-organic sheets by Fe(2+), Co(2+), and Pb(2+). This novel
      transformation was done both randomly and at predetermined patterns defined by
      photolithography to create monolayer sheets composed of different netpoints. All
      transmetalated sheets are mechanically strong enough to be spanned over 20 * 20
      MUm(2) sized holes. Density functional theory calculations provide both a model
      for the molecular structure of an Fe(2+)-based sheet and first insights into how
      transmetalation proceeds. Such transmetalated sheets with random and patterned
      netpoints can be considered as two-dimensional analogues of linear copolymers.
      Their nanoscale synthesis presents an advance in monolayer/polymer chemistry with
      applications in fields such as surface coating, molecular electronics, device
      fabrication, imaging, and sensing. 

PMID- 24673196
TI  - The effects of light at night on circadian clocks and metabolism.
AB  - Most organisms display endogenously produced ~ 24-hour fluctuations in physiology
      and behavior, termed circadian rhythms. Circadian rhythms are driven by a
      transcriptional-translational feedback loop that is hierarchically expressed
      throughout the brain and body, with the suprachiasmatic nucleus of the
      hypothalamus serving as the master circadian oscillator at the top of the
      hierarchy. Appropriate circadian regulation is important for many homeostatic
      functions including energy regulation. Multiple genes involved in nutrient
      metabolism display rhythmic oscillations, and metabolically related hormones such
      as glucagon, insulin, ghrelin, leptin, and corticosterone are released in a
      circadian fashion. Mice harboring mutations in circadian clock genes alter
      feeding behavior, endocrine signaling, and dietary fat absorption. Moreover,
      misalignment between behavioral and molecular circadian clocks can result in
      obesity in both rodents and humans. Importantly, circadian rhythms are most
      potently synchronized to the external environment by light information and
      exposure to light at night potentially disrupts circadian system function. Since
      the advent of electric lights around the turn of the 20th century, exposure to
      artificial and irregular light schedules has become commonplace. The increase in
      exposure to light at night parallels the global increase in the prevalence of
      obesity and metabolic disorders. In this review, we propose that exposure to
      light at night alters metabolic function through disruption of the circadian
      system. We first provide an introduction to the circadian system, with a specific
      emphasis on the effects of light on circadian rhythms. Next we address
      interactions between the circadian system and metabolism. Finally, we review
      current experimental and epidemiological work directly associating exposure to
      light at night and metabolism.

PMID- 24673197
TI  - Primary care research network progress in Scotland.
AB  - Many developed industrialized countries perceive considerable value in developing
      practice based research networks. In this paper, the development of the Scottish
      Primary Care Research Network (SPCRN) from 1924-2013 is described. After a false
      start in the early twentieth century and some local developments 10-15 years ago,
      the Scottish Primary Care Research Network was finally built upon existing
      networks of teaching and training practices centred on research active
      departments of general practice and primary care. This meant that a climate
      already favourable to research existed and several of the necessary skills were
      available. Long-term funding commitment to the network by the National Health
      Service meant that the infrastructure could be developed in the knowledge that it
      would be likely to become incorporated into wider Scottish and UK systems. Two
      thirds of Scottish practices regularly participate in research at a rate of 50-60
      studies each year, which result in a range of publications that influence
      clinical decisions and health policy. As the success of the network grows,
      greater demands are placed upon it, and the capacity of practices to continue to
      engage in research may be tested.

PMID- 24673198
TI  - Cardiovascular aspects of psoriasis: an updated review.

PMID- 24673199
TI  - Genome-wide approach in Arabidopsis thaliana to assess the toxicity of cadmium
      sulfide quantum dots.
AB  - Cadmium sulfide quantum dots (CdS QDs) are used in the manufacture of a number of
      electronics products. Their small size allows their ready entry into living
      cells, but as yet no attempt has been made to assess their toxicity. Our aim was
      to exploit two Ds transposition-induced mutant lines of Arabidopsis thaliana
      which tolerated exposure to CdS QDs to identify the genetic basis of their
      tolerance. Both a genome-wide top-down (from mutant to genes) and a bottom-up
      (from gene expression to phenotype) approach were applied. The differential
      responses of the mutants compared to the wild type showed that sensitivity to CdS
      QDs was unrelated to sensitivity to Cd(2+) ions. A transcriptomic analysis
      identified a number of genes whose transcript abundance was correlated with the
      tolerance. The phenotype of one of the mutants was correlated with the
      overexpression of ELM2, an MYB containing gene visited by a Ds transposon.
      Segregation analysis showed that the genetic basis of CdS QDs tolerance in both
      mutants was monogenic. The phenotype of the other mutant could be explained by
      the mutation of HCF101, a gene involved in photosynthesis. 

PMID- 24673200
TI  - Suppression of the production of transforming growth factor beta1, interleukin
      10, and vascular endothelial growth factor in the B16F10 cells by Ganoderma
      lucidum polysaccharides.
AB  - Transforming growth factor beta (TGF-beta), interleukin-10 (IL-10), and vascular
      endothelial growth factor (VEGF) are three of the commonly studied cytokines
      playing an important role in tumor initiation and progression. Besides their
      promotional effects on tumor progression, the three cytokines have
      immunosuppressive effects that facilitate tumor initiation and progression as
      well. Ganoderma lucidum polysaccharides (Gl-PS) with multiple bioactivities may
      have the effect on B16F10 melanoma cells to induce stronger antitumor immune
      response that has been demonstrated. Gl-PS may have the suppressive effects on
      the production of these three cytokines, which has yet to be demonstrated. In
      this study, we tested these effects of Gl-PS by incubating Gl-PS with malignant
      tumor cells such as B16F10 cells, a melanoma cell line, and LA795 cells, a lung
      carcinoma cell line. RT-qPCR and enzyme-linked immunosorbent assay showed that
      the production of TGF-beta1, IL-10, and VEGF in B16F10 melanoma cells and LA795
      lung carcinoma cells was suppressed by Gl-PS at both mRNA and protein levels,
      suggesting that the suppression on production of TGF-beta, IL-10, and VEGF in
      B16F10 melanoma cells and LA795 lung carcinoma cells by Gl-PS may contribute to
      the therapy on melanoma and lung carcinoma along with the induction of stronger
      antitumor immune response. 

PMID- 24673201
TI  - Spatial ability mediates the gender difference in middle school students' science
      performance.
AB  - Prior research has demonstrated a male advantage in spatial skills and science
      achievement. The present research integrated these findings by testing the
      potential role of spatial skills in gender differences in the science performance
      of eighth-grade students (13-15 years old). In (N = 113), the findings showed
      that mental rotation ability mediated gender differences in physical science and
      technology/engineering test scores. In (N = 73,245), science performance was
      examined in a state population of eighth-grade students. As in , the results
      revealed larger gender differences on items that showed higher correlations with
      mental rotation. These findings underscore the importance of considering spatial
      training interventions aimed at reducing gender differences in the science
      performance of school-aged children. 

PMID- 24673202
TI  - Sensory impairment: a new research imperative.

PMID- 24673206
TI  - Antiparasitic chaiyaphumines from entomopathogenic Xenorhabdus sp. PB61.4.
AB  - A new class of four depsipentapeptides called chaiyaphumines A-D (1-4) was
      isolated from Xenorhabdus sp. PB61.4. Their structures were elucidated by
      detailed 1D and 2D NMR experiments and by a Marfey's analysis following flash
      hydrolysis of the peptide. Verification of the structure was achieved by three
      dimensional modeling using NOE-derived distance constraints, molecular dynamics,
      and energy minimization. Chaiyaphumine A (1) showed good activity against
      Plasmodium falciparum (IC50 of 0.61 MUM), the causative agent of malaria, and was
      active against other protozoal tropical disease causing agents. 

PMID- 24673207
TI  - Novel nanosome delivery system combined with siRNA targeting the antimicrobial
      gene DFB4: a new approach for psoriasis management?
AB  - In a recently published issue of the journal, Bracke et al. demonstrate an
      impressive improvement in psoriasiform features in allogeneic human skin grafts
      transplanted onto immune-deficient mice. This improvement was achieved using a
      novel nanosome (SECosome) as a vehicle for delivering topically applied siRNA to
      human epidermis. Targeting the gene DFB4 with this delivery system, they
      prevented translation of the antimicrobial peptide, human beta defensin-2(hBD2),
      thus normalizing the psoriasiform epidermal phenotype of siRNA/SECosome-treated
      human skin grafts. This study encourages the exploration of topical gene
      silencing strategies in dermatology and refocuses our attention on both, the role
      of hBD2 in psoriasis pathogenesis and the thorny question which animal model
      reflects human psoriasis most faithfully.

PMID- 24673208
TI  - The challenges of caring for children with nephrotic syndrome in a tertiary
      institution in the Democratic Republic of Congo.
AB  - AIM: The care of children with resistant nephrotic syndrome (NS) in the
      Democratic Republic of Congo is compromised by resource deficiencies that range
      from inadequate healthcare budgets, to scarce laboratory facilities and
      inconsistent drug supplies. The aim of this study was to describe the clinical
      profile and management of children with nephrotic syndrome in Kinshasa, the
      country's capital and its largest city. METHODS: We retrospectively reviewed the
      medical records of 62 patients with a diagnosis of NS, who were seen in the
      Paediatric Nephrology Unit at the University Hospital of Kinshasa between January
      1983 and January 2008. RESULTS: Of the 62 children diagnosed with nephrotic
      syndrome, 33 were boys and 29 were girls, giving a male to female ratio of
      1.14:1. Their median age at initial presentation was 7.5 years (range: 1.5-13
      years) with a peak incidence at six to nine years of age (38.7%). No cases of
      plasmodium malariae were isolated in our series. Sixteen (25.8%) of the children
      had resistant corticoid nephrotic syndrome and six of the children (9.7%) died.
      CONCLUSION: Age, the prevalence of steroid-resistant NS and the mortality rate in
      our series were higher than those reported in Asian and Western countries.

PMID- 24673209
TI  - Making room for improvement.

PMID- 24673217
TI  - Creating more time in the day for patient care.

PMID- 24673218
TI  - Staff survey: encouraging, but still areas of concern.

PMID- 24673219
TI  - Trusts helped to become more transparent.

PMID- 24673220
TI  - Marks & Spencer business guru turns his eye to the health service.

PMID- 24673221
TI  - Coaching for life.

PMID- 24673228
TI  - Let's get together.

PMID- 24673232
TI  - How to develop better practice in response to patients' complaints.
AB  - Complaints can give hospital managers valuable insight into patients' experiences
      of care delivery, insight that regular service audits may miss. Viewed
      positively, complaints offer managers an opportunity to develop and improve
      services. This article shares the findings from a Patients Association survey of
      complainants across ten pilot trusts from July 2011 to July 2013. The results
      describe what it feels like to make a complaint and highlight considerable
      variation in performance by the organisations involved. Overall complainant
      satisfaction was found to be low, and approaches that senior nurses can take in
      response are suggested.

PMID- 24673233
TI  - Protected engagement time in mental health inpatient units.
AB  - Protected engagement time in mental health inpatient units is a fixed period each
      day during which administrative activities and visiting are suspended so that
      nurses can focus on individual patient contact. However, there are a number of
      barriers to implementing this strategy effectively, which include high workloads,
      staff shortages and lack of supervision to support therapeutic interventions.
      This article discusses some of these barriers and suggests that managers of acute
      psychiatric units should ensure that patients have appropriate emotional support,
      and that skilled mental health nurses should be supported to devote time to
      therapeutic interventions. 

PMID- 24673234
TI  - A trust-wide review of clinical nurse specialists' productivity.
AB  - The contribution made by clinical nurse specialists (CNSs) to patient care needs
      to be understood fully to provide assurance of effective use of resources.
      However, CNS roles are often poorly understood and not easily articulated. Due to
      the diversity of these roles, robust reviews of performance and economic benefits
      can be regarded as time consuming and resource intense, and many organisations
      enlist external agencies to clarify the contribution to care made by their CNSs.
      This article gives an overview of a Cambridge University Hospitals NHS Foundation
      Trust internal review of CNS roles without the support of an external agency. The
      review provided assurance that this group of nurses is being used effectively and
      identified opportunities to use the role in different ways to increase
      effectiveness. 

PMID- 24673235
TI  - Well-rounded leader.

PMID- 24673236
TI  - Practice effects associated with repeated assessment of a clinical test of
      reaction time.
AB  - CONTEXT: Researchers have confirmed that the ruler-drop test could be included as
      part of a multifaceted concussion-assessment battery and potentially as a way to
      track recovery from head injury. However, it is unclear if this clinical test of
      reaction time would be characterized by inconsistent performance because of
      practice effects. OBJECTIVE: To determine if the ruler-drop test is susceptible
      to practice effects after serial administration. DESIGN: Descriptive laboratory
      study. SETTING: Sports medicine research laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Forty-three persons (age = 21.8 +/- 2.6 years). INTERVENTION(S):
      Ten sessions were completed over 5 weeks. Participants completed 10 trials of the
      ruler-drop test during each session. MAIN OUTCOME MEASURE(S): The mean reaction
      times calculated for all participants from each test session were analyzed to
      determine if there was any meaningful change (ie, improvement) in reaction time
      over the course of the investigation. RESULTS: Simple reaction time improved (ie,
      decreased) after repeated administration of the ruler-drop test, and the most
      pronounced improvement occurred between the first 2 test sessions. Between the
      first and second test sessions, reaction time decreased by almost 7 milliseconds,
      and there was an overall improvement of almost 13 milliseconds between the first
      and tenth sessions. Although the pairwise comparisons between the first and
      second and the first and third sessions were not significant, the change in mean
      reaction time between the first session and most of the other sessions was
      significant. We noted no differences when successive sessions were compared.
      CONCLUSIONS: To prevent practice-related improvements in reaction time,
      practitioners should allow at least 1 practice session before recording baseline
      results on the ruler-drop test.

PMID- 24673237
TI  - Postinjury anxiety and social support among collegiate athletes: a comparison
      between orthopaedic injuries and concussions.
AB  - CONTEXT: When an athlete is injured, the primary focus of the sports medicine
      team is to treat the physical effects of the injury. However, many injured
      athletes experience negative psychological responses, including anxiety,
      regarding their injury. OBJECTIVE: To compare the anxiety and social support of
      athletes with concussions and a matched group of athletes with orthopaedic
      injuries. DESIGN: Cross-sectional study. SETTING: Athletic training room.
      PATIENTS OR OTHER PARTICIPANTS: A total of 525 injuries among athletes from 2 Big
      Ten universities were observed. Of these, 63 concussion injuries were matched
      with 63 orthopaedic injuries for the athlete's sex, sport, and time loss due to
      injury. MAIN OUTCOME MEASURE(S): Clinical measures included the State-Trait
      Anxiety Inventory (which measures both state and trait anxiety) and the modified
      6-item Social Support Questionnaire. RESULTS: The group with concussions relied
      on their family for social support 89% of the time, followed by friends (78%),
      teammates (65%), athletic trainers (48%), coaches (47%), and physicians (35%).
      The group with orthopaedic injuries relied on their family for social support 87%
      of the time, followed by friends (84%), teammates (65%), athletic trainers (57%),
      coaches (51%), and physicians (36%). We found no differences for the State-Trait
      Anxiety Inventory (t = -1.38, P = .193) between the concussed and orthopaedic
      injury groups. Social Support Questionnaire scores were significant predictors
      for postinjury state anxiety. Specifically, increased scores were associated with
      decreased postinjury state anxiety (beta = -4.21, P = .0001). CONCLUSIONS: Both
      the concussed athletes and those with orthopaedic injuries experienced similar
      state and trait anxiety and relied on similar sources of social support
      postinjury. However, athletes with orthopaedic injuries reported greater
      satisfaction with support from all sources compared with concussed athletes. In
      contrast, concussed athletes showed more significant predictor models of social
      support on state anxiety at return to play.

PMID- 24673238
TI  - Strength asymmetry of the shoulders in elite volleyball players.
AB  - CONTEXT: Volleyball players are reported to have shoulder strength imbalances.
      Previous authors have primarily investigated small samples of male players at a
      single skill level, without considering playing position, and with inconsistent
      findings. OBJECTIVE: To evaluate shoulder strength asymmetry and a history of
      shoulder injury in a large sample of professional volleyball players of both
      sexes across different playing positions and skill levels. DESIGN: Descriptive
      laboratory study. PATIENTS OR OTHER PARTICIPANTS: A sample of 183 volleyball
      players (99 men, 84 women). MAIN OUTCOME MEASURE(S): We assessed shoulder
      internal-rotator and external-rotator concentric strength at 60 degrees /s using
      an isokinetic dynamometer and dominant-nondominant differences in shoulder
      strength and strength ratios using repeated-measures analyses of variance. Peak
      torque was normalized for body mass and external-rotation/internal-rotation
      concentric strength. RESULTS: Internal-rotation strength was asymmetric in favor
      of the dominant side in both sexes, regardless of previous shoulder injury
      status. Male volleyball players had a lower shoulder strength ratio on the
      dominant side, regardless of previous shoulder injury status. However, this
      finding was valid only when hand dominance was taken into account. Female
      volleyball players playing at a higher level (ie, first versus second division)
      were 3.43 times more likely to have an abnormal strength ratio. Playing position
      was not associated with an abnormal shoulder strength ratio or strength
      asymmetry. CONCLUSIONS: In male volleyball players, the external
      rotation/internal-rotation strength ratio of the dominant shoulder was lower,
      regardless of playing position, skill level, or a previous shoulder injury. In
      female players, the ratio was less only in those at a higher skill level.
      Although speculative, these findings generally suggest that female volleyball
      players could have a lower risk of developing shoulder-related problems than male
      volleyball players. Isokinetic shoulder testing may reveal important information
      about the possible risk factors for shoulder injuries, so we recommend including
      it in the functional screening of volleyball players.

PMID- 24673240
TI  - Nanomedicines: addressing the scientific and regulatory gap.
AB  - Nanomedicine is the application of nanotechnology to the discipline of medicine:
      the use of nanoscale materials for the diagnosis, monitoring, control,
      prevention, and treatment of disease. Nanomedicine holds tremendous promise to
      revolutionize medicine across disciplines and specialties, but this promise has
      yet to be fully realized. Beyond the typical complications associated with drug
      development, the fundamentally different and novel physical and chemical
      properties of some nanomaterials compared to materials on a larger scale (i.e.,
      their bulk counterparts) can create a unique set of opportunities as well as
      safety concerns, which have only begun to be explored. As the research community
      continues to investigate nanomedicines, their efficacy, and the associated safety
      issues, it is critical to work to close the scientific and regulatory gaps to
      assure that nanomedicine drives the next generation of biomedical innovation. 

PMID- 24673239
TI  - Isolation and characterization of an obligately chemolithoautotrophic
      Halothiobacillus strain capable of growth on thiocyanate as an energy source.
AB  - Molecular and microbiological analysis of a laboratory bioreactor biomass
      oxidizing thiocyanate at autotrophic conditions and at 1 M NaCl showed a
      domination of a single chemolithoautotrophic sulfur-oxidizing bacterium (SOB)
      capable of using thiocyanate as an energy source. The bacterium was isolated in
      pure cultures and identified as a member of the Halothiobacillus
      halophilus/hydrothermalis clade. This clade includes moderately halophilic
      chemolithoautotrophic SOB from marine and hypersaline habitats for which the
      ability to utilize thiocyanate as an electron donor has not been previously
      demonstrated. Halothiobacillus sp. strain SCN-R1 grew with thiocyanate as the
      sole energy and nitrogen source oxidizing it to sulfate and ammonium via the
      cyanate pathway. The pH range for thiocyanate oxidation was within a neutral
      region between 7 and 8 and the range of salinity was from 0.2 to 1.5 M NaCl, with
      an optimum at 0.5 M. Despite the close phylogenetic relatedness, none of the
      tested type strains and other isolates from the H. halophilus/hydrothermalis
      group exhibited thiocyanate-oxidizing capacity. 

PMID- 24673241
TI  - Accelerated stability assay (ASA) for colloidal systems.
AB  - Assessment of the stability of colloidal systems, in particular lyotropic liquid
      crystalline dispersions, such as cubosomes and hexosomes, is typically performed
      qualitatively or with limited throughput on specialized instruments. Here, an
      accelerated stability assay for colloidal particles has been developed in 384
      well plates with standard laboratory equipment. These protocols enable
      quantitative assessments of colloidal stability. To demonstrate the applicability
      of the assay, several steric stabilizers for cubic phase nanostructured particles
      (cubosomes) have been compared to the current "gold standard" Pluronic F127. 

PMID- 24673242
TI  - Elastomeric negative acoustic contrast particles for capture, acoustophoretic
      transport, and confinement of cells in microfluidic systems.
AB  - We present a particle-based method for the immunospecific capture and confinement
      of cells using acoustic radiation forces. Ultrasonic standing waves in
      microfluidic systems have previously been used for the continuous focusing of
      cells in rapid screening and sorting applications. In aqueous fluids, cells
      typically exhibit positive acoustic contrast and are thus forced toward the
      pressure nodes of a standing wave. Conversely, elastomeric particles exhibit
      negative acoustic contrast and travel toward the pressure antinodes. We have
      developed a class of elastomeric particles that are synthesized in bulk using a
      simple nucleation and growth process, providing precise control over their size
      and functional properties. We demonstrate that the biofunctionalization of these
      particles can allow the capture and transport of cells to the pressure antinodes
      solely via acoustic radiation forces, which may enable new acoustics-based cell
      handling techniques such as the washing, labeling, and sorting of cells with
      minimal preparatory steps. 

PMID- 24673243
TI  - Photochemical transformation and photoinduced toxicity reduction of silver
      nanoparticles in the presence of perfluorocarboxylic acids under UV irradiation.
AB  - The impact of perfluorocarboxylic acids (PFCAs) with carbon chain length C2 to C8
      on the dissolution, aggregation, reactive oxygen species (ROS) generation, and
      toxicity of citrate-coated AgNPs was investigated under UV irradiation. The
      presence of PFCAs decreased dissolution, aggregation, ROS generation, and
      toxicity of AgNPs because the negatively charged PFCAs sorbed on AgNP surface
      enhanced their stability. Both dissolution and aggregation rate of AgNPs
      decreased with chain length of PFCAs under UV irradiation, primarily because
      PFCAs with longer chain length sorbed on AgNP surface could form thicker
      coatings. The dissolution of AgNPs followed pseudo-first-order kinetics, and the
      rate constant decreased from 0.58 h(-1) with C2 to 0.30 h(-1) with C8. The
      hydrodynamic diameters of AgNPs linearly increased under UV irradiation with
      aggregation rates ranged from 72.1 to 143.5 nm/h. O2(*-) generation was observed
      in AgNP suspension with quantum yield of 0.12%, but was completely suppressed by
      PFCAs because they inhibited the interaction between photoelectrons and O2. A
      linear correlation was established between dissolved Ag(+) and bacterial survival
      rates of AgNPs with and without PFCAs under UV irradiation. This study highlights
      the necessity of considering coexisting organic contaminants when investigating
      the environmental behaviors of AgNPs.

PMID- 24673244
TI  - MUTATIONISM 2.0: VIEWING EVOLUTION THROUGH MUTATION'S LENS.

PMID- 24673245
TI  - Drug survival is not significantly different between biologics in patients with
      psoriasis vulgaris: a single-centre database analysis.
AB  - BACKGROUND: Drug survival depends on several factors such as dosing,
      effectiveness, quality-of-life improvement and safety, and could be seen as an
      overall marker for treatment success. Such data for biologics in psoriasis
      treatment are sparse. OBJECTIVES: To determine differences in drug survival
      between different biologics for psoriasis. METHODS: Drug survival, dosing,
      Psoriasis Area and Severity Index (PASI) and Skindex-29 at weeks 12 and 52, and
      adverse events of patients with psoriasis treated with a biologic registered in
      the local database of the Academic Medical Center, Amsterdam, were analysed.
      Patients were divided into those naive or non-naive for treatment episodes with
      biologics. RESULTS: Drug survival did not differ significantly for naive
      treatment episodes between the biologics (etanercept 85% to 64%, adalimumab 77%
      to 77%, infliximab 75% to 75% for year 1-4), or for non-naive treatment episodes
      (etanercept 86% to 42%, adalimumab 84% to 56%, infliximab 68% to 43% for year 1
      4; ustekinumab 84% to 57% for year 1-3). The naive group showed better drug
      survival and PASI 75 response at week 12, although the difference was not
      significant. A similar improvement of mean ?PASI and mean ?Skindex-29 was
      observed at weeks 12 and 52 for all biologics for both groups, although no
      significant difference was seen between groups. Treatment termination was due
      mainly to nonresponse for all biologics. CONCLUSIONS: There was no significant
      difference in drug survival, mean ?PASI or Skindex-29 response at weeks 12 or 52
      between the biologics or between the naive and non-naive groups. Treatment
      termination was due mostly to nonresponse. Sequential treatment with the
      available biologics can be effective.

PMID- 24673246
TI  - Effect of psychological stress on fertility hormones and seminal quality in male
      partners of infertile couples.
AB  - The present study evaluated the effect of psychological stress on male fertility
      hormones and seminal quality in male partner of infertile couples. Seventy male
      partners of infertile couples were evaluated for level of psychological stress
      using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total
      testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) by
      electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was
      performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and
      depression score >=8 (abnormal HADS score). The persons having abnormal HADS had
      lower serum total testosterone, higher serum FSH and LH than those of persons
      having normal HADS. Serum total testosterone correlated negatively with HADS, but
      LH and FSH correlated positively. There was no change in GnRH with the change in
      stress or testosterone levels. Sperm count, motility and morphologically normal
      spermatozoa were lower in persons having abnormal HADS. Sperm count correlated
      positively with total testosterone and negatively with FSH and LH. Abnormal sperm
      motility and morphology were related to lower testosterone and higher LH and FSH
      levels. Psychological stress primarily lowers serum total testosterone level with
      secondary rise in serum LH and FSH levels altering seminal quality. Stress
      management is warranted for male infertility cases. 

PMID- 24673247
TI  - A metasynthesis of published case studies through Lacan's L-schema: Transference
      in perversion.
AB  - Transference in perversion is characterized by specific problems such as a
      defiant and polemic attitude, erotic transference, projections, and aggression.
      Such transference poses particular problems in the treatment of perversion and
      might render analytical work with these patients impossible. The authors propose
      that Lacan's L-schema can contribute to separating productive from
      counterproductive aspects of transference as it distinguishes between an
      Imaginary and a Symbolic dimension in transference. In this meta-synthesis of 11
      published case studies on sexual perversion, patterns of transference are
      analysed. On the Imaginary dimension, the authors found that patients with
      perversion tend to (un)consciously engage the analyst in a relationship
      characterized by identification, fusion and rivalry. On the Symbolic dimension,
      they found that perverse patients are able to question their motives, lapses,
      symptoms, and subjective identity. The thematic analysis revealed the importance
      of the position of the analyst in this work, which is described within the L
      schema as being the representative of the otherness in the Other. Implications
      for clinical practice and recommendations for further research are outlined. 

PMID- 24673248
TI  - Developing a typology of African Americans with limited literacy based on
      preventive health practice orientation: implications for colorectal cancer
      screening strategies.
AB  - Preventive health messages are often tailored to reach broad sociodemographic
      groups. However, within groups, there may be considerable variation in
      perceptions of preventive health practices, such as colorectal cancer screening.
      Segmentation analysis provides a tool for crafting messages that are tailored
      more closely to the mental models of targeted individuals or subgroups. This
      study used cluster analysis, a psychosocial marketing segmentation technique, to
      develop a typology of colorectal cancer screening orientation among 102 African
      American clinic patients between the ages of 50 and 74 years with limited
      literacy. Patients were from a general internal medicine clinic in a large urban
      teaching hospital, a subpopulation known to have high rates of colorectal cancer
      and low rates of screening. Preventive screening orientation variables included
      the patients' responses to questions involving personal attitudes and preferences
      toward preventive screening and general prevention practices. A k-means cluster
      analysis yielded three clusters of patients on the basis of their screening
      orientation: ready screeners (50.0%), cautious screeners (30.4%), and fearful
      avoiders (19.6%). The resulting typology clearly defines important subgroups on
      the basis of their preventive health practice perceptions. The authors propose
      that the development of a validated typology of patients on the basis of their
      preventive health perceptions could be applicable to a variety of health
      concerns. Such a typology would serve to standardize how populations are
      characterized and would provide a more accurate view of their preventive health
      related attitudes, values, concerns, preferences, and behaviors. Used with
      standardized assessment tools, it would provide an empirical basis for tailoring
      health messages and improving medical communication. 

PMID- 24673249
TI  - High-density nucleosome occupancy map of human chromosome 9p21-22 reveals
      chromatin organization of the type I interferon gene cluster.
AB  - Genome-wide investigations have dramatically increased our understanding of
      nucleosome positioning and the role of chromatin in gene regulation, yet some
      genomic regions have been poorly represented in human nucleosome maps. One such
      region is represented by human chromosome 9p21-22, which contains the type I
      interferon gene cluster that includes 16 interferon alpha genes and the single
      interferon beta, interferon epsilon, and interferon omega genes. A high-density
      nucleosome mapping strategy was used to generate locus-wide maps of the
      nucleosome organization of this biomedically important locus at a steady state
      and during a time course of infection with Sendai virus, an inducer of interferon
      gene expression. Detailed statistical and computational analysis illustrates that
      nucleosomes in this locus exhibit preferences for particular dinucleotide and
      oligomer DNA sequence motifs in vivo, which are similar to those reported for
      lower eukaryotic nucleosome-DNA interactions. These data were used to visualize
      the region's chromatin architecture and reveal features that are common to the
      organization of all the type I interferon genes, indicating a common nucleosome
      mediated gene regulatory paradigm. Additionally, this study clarifies aspects of
      the dynamic changes that occur with the nucleosome occupying the transcriptional
      start site of the interferon beta gene after virus infection. 

PMID- 24673250
TI  - A new semisynthetic derivative of sauroine induces LTP in hippocampal slices and
      improves learning performance in the Morris Water Maze.
AB  - Two semisynthetic acetyl derivatives of the alkaloid sauroine from Huperzia
      saururus, monoacetyl sauroine, and diacetyl sauroine (DAS) were obtained and
      their chemical structures were analyzed by NMR. While monoacetyl sauroine is the
      typical product of acetylation, DAS is an unexpected derivative related to the
      keto-enol formation of sauroine. Recordings of field excitatory post-synaptic
      potentials from the CA1 region of rat hippocampal slices showed that only DAS
      acutely applied induced chemical long-term potentiation (LTP) in a dose-dependent
      manner with an EC50 of 1.15 +/- 0.09 MUM. This effect was blocked by 10 MUM D(-)
      2-amino-5-phosphonopentanoic acid (AP5), suggesting dependence on the NMDA
      receptor. DAS significantly increased NMDA receptor-dependent excitatory post
      synaptic currents without affecting alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate receptor-dependent currents. Repetitive administration of DAS improved
      visuo-spatial learning in the Morris Water Maze. In slices from rats tested in
      the Morris Water Maze, LTP resulting from electrical synaptic stimulation was 2.5
      times larger than in controls. Concentration of DAS measured in the brain after
      repetitive administration was 29.5 MUM. We conclude that slices perfused with DAS
      display a robust NMDA receptor-dependent chemical LTP. During chronic treatment,
      DAS enhances learning abilities through a metaplastic mechanism as revealed by
      the augmentation of LTP in slices. DAS, therefore, may be a promising compound as
      a nootropic therapeutic drug. A semisynthetic derivative of sauroine, diacetyl
      sauroine (DAS), induces chemical long-term potentiation in rat hippocampal slices
      increasing the NMDA receptor-dependent current. 2 mg/kg prior to each session in
      a Morris Water Maze (MWM) improves behavior performance. In slices prepared from
      the tested rats the electrical stimulation-dependent long-term potentiation (LTP)
      was greatly enhanced. Therefore, DAS may have potency as a nootropic drug against
      the memory decline.

PMID- 24673251
TI  - Metal oxide affinity chromatography platform-polydopamine coupled functional two
      dimensional titania graphene nanohybrid for phosphoproteome research.
AB  - In this work, a facile route was initially developed for preparation of a novel
      metal oxide affinity chromatography (MOAC) material by grafting titania
      nanoparticles on polydopamine (PD)-coated graphene (denoted as G@PD@TiO2). In the
      first step, self-assemble polymerization of dopamine on graphene was performed in
      basic solution at room temperature, which not only offered the coupling linker
      between titania and graphene but also improved the hydrophilicity and biological
      compatibility of the nanohybrids. Thereafter, the titania nanoparticles were
      grafted on the surface of the PD-coated graphene via a simple hydrothermal
      treatment. The as-prepared G@PD@TiO2 nanohybrids exhibited high sensitivity
      (detection limit of 5 fmol) and high selectivity for phosphopeptides at a low
      molar ratio of phosphopeptides/nonphosphopeptides (1:1000). Moreover, the as
      prepared nanohybrids were also investigated for enrichment of phosphopeptides
      from real biological samples (human serum and mouse brain). A total number of 556
      phosphorylation sites were identified from the digest of mouse brain proteins,
      showing great potential in the practical application. 

PMID- 24673252
TI  - Room-temperature half-metallicity in La(Mn,Zn)AsO alloy via element
      substitutions.
AB  - Exploring half-metallic materials with high Curie temperature, wide half-metallic
      gap, and large magnetic anisotropy energy is one of the effective solutions to
      develop high-performance spintronic devices. Using first-principles calculations,
      we design a practicable half-metal based on a layered La(Mn0.5Zn0.5)AsO alloy via
      element substitutions. At its ground state, the pristine La(Mn0.5Zn0.5)AsO alloy
      is an antiferromagnetic semiconductor. Either hole doping via
      (Ca(2+)/Sr(2+),La(3+)) substitutions or electron doping via (H(-)/F(-),O(2-))
      substitutions in the [LaO](+) layer induce half-metallicity in the
      La(Mn0.5Zn0.5)AsO alloy. The half-metallic gap is as large as 0.74 eV. Monte
      Carlo simulations based on the Ising model predict a Curie temperature of 475 K
      for 25% Ca doping and 600 K for 50% H doping, respectively. Moreover, the quasi
      two-dimensional structure endows the doped La(Mn,Zn)AsO alloy a sizable magnetic
      anisotropy energy with the magnitude of at least one order larger than those of
      Fe, Co, and Ni bulks. 

PMID- 24673253
TI  - Roseola infantum and its causal human herpesviruses.
AB  - Roseola infantum, also known as exanthem subitum or sixth disease, is a generally
      benign febrile exanthem of infancy. It has a characteristic clinical course of
      high fever followed by the appearance of an exanthem upon defervescence. Febrile
      seizures are a frequent complication. Roseola is caused by infection with human
      herpesviruses 6 or 7 (HHV-6/7), which are acquired at a young age. Diagnosis is
      made by serology or by virus detection in body fluids and tissues. Treatment of
      roseola is supportive; recovery is usually complete with no significant sequelae.
      However, HHV-6/7 can reactivate in immunocompetent as well as immunocompromised
      individuals with severe systemic consequence.

PMID- 24673254
TI  - Development of a metabolomic radiation signature in urine from patients
      undergoing total body irradiation.
AB  - The emergence of the threat of radiological terrorism and other radiological
      incidents has led to the need for development of fast, accurate and noninvasive
      methods for detection of radiation exposure. The purpose of this study was to
      extend radiation metabolomic biomarker discovery to humans, as previous studies
      have focused on mice. Urine was collected from patients undergoing total body
      irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem
      cell transplantation at 4-6 h postirradiation (a single dose of 1.25 Gy) and 24 h
      (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained
      through analysis with ultra performance liquid chromatography coupled to time-of
      flight mass spectrometry (TOFMS). Prior to further analyses, each sample was
      normalized to its respective creatinine level. Statistical analysis was conducted
      by the nonparametric Kolmogorov-Smirnov test and the Fisher's exact test and
      markers were validated against pure standards. Seven markers showed distinct
      differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine
      and the carnitine conjugates acetylcarnitine, decanoylcarnitine and
      octanoylcarnitine play an important role in the transportation of fatty acids
      across mitochondria for subsequent fatty acid beta-oxidation. The remaining
      metabolites, hypoxanthine, xanthine and uric acid are the final products of the
      purine catabolism pathway, and high levels of excretion have been associated with
      increased oxidative stress and radiation induced DNA damage. Further analysis
      revealed sex differences in the patterns of excretion of the markers,
      demonstrating that generation of a sex-specific metabolomic signature will be
      informative and can provide a quick and reliable assessment of individuals in a
      radiological scenario. This is the first radiation metabolomics study in human
      urine laying the foundation for the use of metabolomics in biodosimetry and
      providing confidence in biomarker identification based on the overlap between
      animal models and humans. 

PMID- 24673255
TI  - (28)Silicon radiation-induced enhancement of synaptic plasticity in the
      hippocampus of naive and cognitively tested mice.
AB  - The space radiation environment consists of multiple species of high-energy
      charge particles (HZE), including (56)Fe and (28)Si nuclei, that may impact
      neuronal cells, but their damaging effects on the central nervous system (CNS)
      have been poorly defined. Hippocampus-dependent memory functions have been shown
      to be highly sensitive to (56)Fe HZE particles, which poses a significant risk to
      the cognitive performance of astronauts during space missions. While low doses of
      (56)Fe radiation do not induce cell death of mature neurons, they affect synaptic
      plasticity in the CA1 region, the principal neuronal output of the hippocampal
      formation involved in memory formation. The effects of (28)Si on the CNS have not
      been defined. Compared to behaviorally naive mice, cognitive testing might affect
      synaptic plasticity and the effects of (28)Si radiation on synaptic plasticity
      might be modulated by prior cognitive testing. Therefore, in the current study,
      we quantified the effects of whole-body (28)Si radiation (600 MeV/n, 0.25 and 1
      Gy) on hippocampus-dependent contextual freezing and synaptic plasticity in the
      CA1 region of animals not exposed (behaviorally naive mice) and animals exposed
      to the contextual freezing test (cognitively tested mice). In behaviorally naive
      mice exposed to 0.25 and 1 Gy of (28)Si radiation, the magnitude of long-term
      potentiation (LTP) was enhanced. However, in mice irradiated with 0.25 Gy
      contextual fear conditioning was enhanced and was associated with a further
      enhancement of the LTP magnitude. Such increase in synaptic plasticity was not
      seen in cognitively tested mice irradiated with 1 Gy. Thus, low dose (28)Si
      radiation has effects on synaptic plasticity in the CA1 region of the hippocampus
      and these effects are modulated by cognitive testing in a contextual fear
      conditioning test. 

PMID- 24673256
TI  - Analysis of the lymphocytopoiesis dynamics in nonirradiated and irradiated
      humans: a modeling approach.
AB  - In this work, a recently developed mathematical model of the lymphocytopoietic
      system in acutely irradiated humans was extended to predict the dynamics of this
      system both in nonirradiated and acutely/chronically irradiated humans. The
      mathematical implementation of this model is a system of nonlinear ordinary
      differential equations, whose variables and parameters have clear biological
      meaning. We demonstrate that the model is capable of reproducing the dynamic
      regimes that are typical for lymphocytopoiesis in nonirradiated individuals with
      a hematological disorder (cyclic lymphocytopenia) and in patients receiving
      allogeneic stem cell transplantation. The model is also capable of predicting the
      dynamics of the lymphocytopoietic system in humans exposed to acute and chronic
      irradiation over a wide range of doses and dose rates. Additionally, the "lethal"
      dose rate of chronic irradiation, evaluated in the framework of the
      lymphocytopoiesis model, agrees with the actual minimum dose rate of lethal
      chronic irradiation observed for humans. 

PMID- 24673258
TI  - Identification of novel sRNAs in Brucella abortus 2308.
AB  - Involved in diverse biological processes, bacterial sRNAs are novel regulators of
      gene expression involved in a wide array of biological processes. To identify
      sRNAs in Brucella abortus, we performed a genome-wide computational prediction
      with integrated SIPHT and NAPP results. In total, 129 sRNA candidates were
      identified, of which 112 were novel sRNA. Twenty novel sRNA candidates were
      tested by RT-PCR and seven could be verified. The putative targets of these sRNAs
      were also predicted and verified. This study provides a significant resource for
      the future study of sRNAs, as well as how sRNAs influence B. abortus physiology
      and pathogenesis.

PMID- 24673259
TI  - Do paediatric residents have the skills to 'lead' newborn resuscitations?

PMID- 24673260
TI  - Trajectories of Indonesian adolescents' religiosity, problem behavior, and
      friends' religiosity: covariation and sequences.
AB  - Changes in religiosity, problem behavior, and their friends' religiosity over a 2
      year period were assessed in a sample of five hundred and fifty-nine 15-year-old
      Indonesian Muslim adolescents. Adolescents self-reported their religiosity,
      problem behavior, and friendships; the religiosity of mutual friends came from
      friends' self-reports. A parallel process analysis of growth curves showed that
      adolescents' religiosity trajectories covaried with both problem behavior and
      friends' religiosity. Using a cross-lagged model in which prior levels were
      controlled, religiosity at 10th and 11th grades predicted friends' religiosity 1
      year later, suggesting that adolescents select friends of similar religiosity.
      This study provides evidence that religion is intertwined with other aspects of
      adolescent development and illustrates the importance of contextualizing
      adolescent religiosity within an ecological framework. 

PMID- 24673257
TI  - Molecular imaging of tumor hypoxia with positron emission tomography.
AB  - The problem of tumor hypoxia has been recognized and studied by the oncology
      community for over 60 years. From radiation and chemotherapy resistance to the
      increased risk of metastasis, low oxygen concentrations in tumors have caused
      patients with many types of tumors to respond poorly to conventional cancer
      therapies. It is clear that patients with high levels of tumor hypoxia have a
      poorer overall treatment response and that the magnitude of hypoxia is an
      important prognostic factor. As a result, the development of methods to measure
      tumor hypoxia using invasive and noninvasive techniques has become desirable to
      the clinical oncology community. A variety of imaging modalities have been
      established to visualize hypoxia in vivo. Positron emission tomography (PET)
      imaging, in particular, has played a key role for imaging tumor hypoxia because
      of the development of hypoxia-specific radiolabelled agents. Consequently, this
      technique is increasingly used in the clinic for a wide variety of cancer types.
      Following a broad overview of the complexity of tumor hypoxia and measurement
      techniques to date, this article will focus specifically on the accuracy and
      reproducibility of PET imaging to quantify tumor hypoxia. Despite numerous
      advances in the field of PET imaging for hypoxia, we continue to search for the
      ideal hypoxia tracer to both qualitatively and quantitatively define the tumor
      hypoxic volume in a clinical setting to optimize treatments and predict response
      in cancer patients. 

PMID- 24673262
TI  - The deubiquitinase A20 in immunopathology of autoimmune diseases.
AB  - Deubiquitination-mediated regulation is important for homeostatic NF-kappaB
      activation. Aberrant NF-kappaB activation associated with various inflammatory
      and autoimmune disorders is linked with defects in the deubiquitinase A20. A20 is
      an important anti-inflammatory molecule that is induced by multiple signals and
      has numerous targets. Polymorphisms within the A20 locus or its altered
      expression are thought to contribute in development of autoimmune disorders.
      Further various studies in mice models underscore the biological importance of
      A20 in prevention of inflammatory conditions. Dysregulated A20 is also been
      suggested as a link between prolonged inflammation and cancer by preliminary
      reports. This review summarizes the existing understanding and focuses on the new
      developments in the field of A20 biology. These developments highlight the
      importance of A20 in pathophysiology of autoimmune disorders and its scope as
      therapeutics and a biomarker.

PMID- 24673261
TI  - AABB validation study of the CDC's National Healthcare Safety Network
      Hemovigilance Module adverse events definitions protocol.
AB  - BACKGROUND: The utility of a hemovigilance system depends on appropriate,
      reproducible application of system definitions. This is even more important when
      submissions are not reviewed by an adjudicating body. We sought to determine how
      participants would code adverse reactions at institutions that had or had not
      received training on the application of definitions used in the CDC's National
      Healthcare Safety Network Hemovigilance Module (HVM). STUDY DESIGN AND METHODS:
      Facilities that were (11) or were not (11) submitting adverse reaction data to
      the HVM reviewed 36 hypothetical cases containing elements of 37 case definitions
      from 12 different diagnostic groups. Respondents were required to determine the
      type of adverse event, if any, and assign a case definition (diagnostic
      probability), severity, and imputability using the January 2013 HVM Surveillance
      Protocol definitions. Those submitting HVM data had access to an instructional
      slide set prepared by CDC using similar hypothetical cases. Concordance with
      expert analysis was determined for the two groups of respondents. RESULTS: The
      frequencies of agreement with the expert assessment were not different according
      to prior training exposure in any of the diagnostic groups, and results were
      totaled across both groups. Response accuracy varied by type of categorization
      (adverse event type, 72.1%; match with case definition, 76.5%; severity, 69.6%;
      imputablity, 64.4%) and by type of adverse event. CONCLUSION: Despite delineated
      definitions, considerable variability in responses was seen, and this was not
      reduced by the available training. This degree of inconsistency in application of
      the surveillance definitions could degrade the utility of comparative reports.

PMID- 24673263
TI  - Preparation, characterization and in vivo evaluation of nanoemulsions for the
      controlled delivery of the antiobesity agent N-oleoylethanolamine.
AB  - > AIMS: N-oleoylethanolamine (OEA) is a lipid mediator that acts as a satiety
      factor. The main limiting factor for its administration is its poor water
      solubility. We designed and characterized new nanoemulsions as delivery system
      for hydrophobic compounds such as OEA. MATERIALS & METHODS: The nanoemulsion
      components and preparation methods were selected in order to achieve the desired
      final properties. Then, we evaluated the in vivo properties of the nanoemulsions
      as drug-delivery systems testing the anorectic effects of OEA in rats after both
      intragastric and intraperitoneal administration. The in vivo toxicity of the
      nanoemulsions was evaluated after a 3-week treatment. RESULTS: Nanoemulsions
      proved to be stable, nontoxic and had no effect on feeding behavior when
      administered without OEA. The effects of OEA were observable after its oral and
      parenteral administration with the nanoemulsions to 24-h fasted rats, finding a
      better efficacy compared with a vehicle containing Tween((r)) 20 (Sigma-Aldrich,
      MO, USA) after oral administration. CONCLUSION: These results support the
      efficacy of these nanoemulsions to deliver highly hydrophobic bioactive drugs.

PMID- 24673264
TI  - Highly versatile immunostimulating nanocapsules for specific immune potentiation.
AB  - AIM: To develop a new core-shell type (nanocapsules) adjuvant system composed of
      squalene and polyglucosamine (PG) and to evaluate its immunostimulant capacity.
      RESULTS: The defined PG nanocapsules exhibited the capacity to efficiently
      associate the selected antigens (recombinant hepatitis B surface antigen and
      hemagglutinin of influenza virus) onto their polymeric surface (70-75%), and the
      immunostimulant imiquimod within the oily core. The resulting nanovaccines, with
      a particle size of 200-250 nm and a positive zeta-potential (~+60 mV), were able
      to significantly potentiate and modulate the immune response to the selected
      antigens upon intramuscular administration to mice. Their efficacy as novel
      adjuvants was attributed to their enhanced cell internalization and effective
      intracellular imiquimod/antigen delivery, together with their prolonged residence
      time at the injection site. CONCLUSION: The nanocapsules described herein have
      the capacity to enhance, prolong and modulate the immune response of subunit
      antigens and, therefore, they could be proposed as a platform for the codelivery
      of different antigens and immunostimulators.

PMID- 24673265
TI  - Brief overview of selected approaches in targeting pancreatic adenocarcinoma.
AB  - INTRODUCTION: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any
      major malignancy, with 5-year survival painfully inadequate at under 5%.
      Investigators have struggled to target and exploit PDAC unique biology, failing
      to bring meaningful results from bench to bedside. Nonetheless, in recent years,
      several promising targets have emerged. AREAS COVERED: This review will discuss
      novel drug approaches in development for use in PDAC. The authors examine the
      continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas),
      which have recently been successfully abated using novel small interfering RNA
      (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC
      including those downstream of mutated KRas, such as MAPK kinase and
      phosphatidylinositol 3-kinase. EXPERT OPINION: Although studies into novel
      biomarkers and advanced imaging have highlighted the potential new avenues toward
      discovering localized tumors earlier, the current therapeutic options highlight
      the fact that PDAC is a highly metastatic and chemoresistant cancer that often
      must be fought with virulent, systemic therapies. Several newer approaches,
      including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan
      with PEGylated hyaluronidase are particularly exciting given their early stage
      results. Further research should help in elucidating their potential impact as
      therapeutic options.

PMID- 24673266
TI  - Diffusive gradients in thin films technique provide robust prediction of metal
      bioavailability and toxicity in estuarine sediments.
AB  - Many sediment quality assessment frameworks incorporate contaminant
      bioavailability as a critical factor regulating toxicity in aquatic ecosystems.
      However, current approaches do not always adequately predict metal
      bioavailability to organisms living in the oxidized sediment surface layers. The
      deployment of the diffusive gradients in thin films (DGT) probes in sediments
      allows labile metals present in pore waters and weakly bound to the particulate
      phase to be assessed in a time-integrated manner in situ. In this study,
      relationships between DGT-labile metal fluxes within 5 mm of the sediment-water
      interface and lethal and sublethal effects to the amphipod Melita plumulosa were
      assessed in a range of contaminated estuarine sediments during 10-day laboratory
      based bioassays. To account for differing toxicities of metals, DGT fluxes were
      normalized to water (WQG) or sediment quality guidelines or toxicity thresholds
      specific for the amphipod. The better dose-response relationship appeared to be
      the one based on WQG-normalized DGT fluxes, which successfully predicted toxicity
      despite the wide range of metals and large variations in sediment properties. The
      study indicated that the labile fraction of metals measured by DGT is useful for
      predicting metal toxicity to benthic invertebrates, supporting the applicability
      of this technique as a rapid monitoring tool for sediments quality assessments. 

PMID- 24673268
TI  - Editorial.

PMID- 24673269
TI  - Introduction to From Copenhagen to the consulting room: complementarity,
      synchronicity and neural coupling.

PMID- 24673267
TI  - The need to look at antibiotic resistance from a health systems perspective.
AB  - Current use, misuse, and overuse of antibiotics raise dangers and ethical
      dilemmas that cannot be solved in isolation, exclusively within a health system
      building block or even within the health sector only. There is a need to tackle
      antibiotic resistance emergence and containment on levels ranging from
      individuals, households, and the communities, to health care facilities, the
      entire health sector, and finally to national and global levels. We analyse
      emergence of antibiotic resistance based on interdependencies between health
      systems resources. We further go beyond the health system building blocks, to
      look at determinants of antibiotic resistance referring to wider global dynamics.
      Multi-level governance is the key for successful action in containment
      strategies. This will involve, in a comprehensive way, patients, health
      facilities where they receive care, health systems to which these facilities
      pertain, and the wider national context as well as the global community that
      influences the functioning of these health systems. In order to be effective and
      sustainable in both high and low-resource settings, implementation of containment
      interventions at all these levels needs to be managed based on existing theories
      and models of change. Although ministries of health and the global community must
      provide vision and support, it is important to keep in mind that containment
      interventions for antibiotic resistance will target individuals, consumers as
      well as providers.

PMID- 24673270
TI  - Psychic energy and synchronicity.
AB  - Given Jung's interest in physics' formulations of psychic energy and the concept
      of time, overlaps and convergences in the themes addressed in analytical
      psychology and in quantum physics are to be expected. These are informed by the
      active intersections between the matter of mind and mindfulness re matter. In
      1911, Jung initiated dinners with Einstein. Jung's definition of libido in the
      pivotal 1912 Fordham Lectures reveals the influence of these conversations.
      Twenty years later, a significant period in physics, Wolfgang Pauli contacted
      Jung. Their collaboration led to the theory of synchronicity. 

PMID- 24673271
TI  - From Copenhagen to the consulting room: Pauli and Jung in Copenhagen.
AB  - In this paper the city of Copenhagen is used as a starting point to highlight
      some critical historical events, both concerning the exchange of ideas between
      the physicist Wolfgang Pauli and C.G. Jung and the history of psychotherapy in
      Scandinavia. Pauli's years in Copenhagen under the influence of Niels Bohr and
      his philosophy prepared him mentally to receiveC.G. Jung's ideas. The paper also
      recounts the one occasion that Jung was in Scandinavia, attending the 9th
      conference of the General Medical Society for Psychotherapy in Copenhagen, just
      before going to New York in 1937 to give his final seminars on Pauli's dreams.
      The reason for focusing on these particular events is that they also constitute
      part of the history of the reception of psychodynamic psychology in Sweden and
      Scandinavia. 

PMID- 24673272
TI  - The cultural significance of synchronicity for Jung and Pauli.
AB  - This paper considers the cultural significance of C.G. Jung's concept of
      synchronicity, as this was envisaged both by Jung himself and by the physicist
      Wolfgang Pauli, Jung's most important discussant in developing the concept. For
      both thinkers the principle of synchronicity was, above all, an attempt to
      develop an expanded, more holistic understanding of science. The paper argues,
      however, that their motives for proposing this development were not just, as
      might be expected, scientific, philosophical, and psychological (including
      personal), but also historical, social, political, and religious, and involved
      consideration of esoteric as well as mainstream currents of thought. 

PMID- 24673273
TI  - Psychophysical correlations, synchronicity and meaning.
AB  - The dual-aspect framework which Jung developed with Wolfgang Pauli implies that
      psychophysical phenomena are neither reducible to physical processes nor to
      conscious mental activity. Rather, they constitute a radically novel kind of
      phenomena, deriving from correlations between the physical and the mental. In
      synchronistic events, a particular subclass of psychophysical phenomena, these
      correlations are explicated as experienced meaning. 

PMID- 24673274
TI  - 'Who am I?'.
AB  - The dreams and existential questions of those, who came into being in order to
      replace a dead person, pivot around a central cry: 'Who am I?' If conceived, born
      or designated as a replacement child, such an individual may suffer-even as an
      adult-from a rarely recognized unconscious confusion of identity, compounded by
      grief and survivors' guilt. From before the child is born, the archetypal forces
      of death and life are joined in a fateful constellation; the soul of the
      replacement child bears the shadow of death from the very beginning of life. Hope
      for the replacement child lies in an emergence of true self as soul recreates
      original life. Analysis can help the replacement child experience a 'rebirth into
      true life', not as 'the one who returned', but as a psychologically newborn
      individual; the path of individuation countering the replacement child's
      identification with the dead. Jungian analysis offers unique concepts for
      understanding and healing the replacement child; C.G. Jung himself was born after
      two stillborn babies and an infant that lived only five days. 

PMID- 24673275
TI  - The Great Mother and the Terrible Mother: mimesis, alterity and attachment in
      adolescence.
AB  - This paper discusses attachment, the longing for familiarity and sameness
      (mimesis), the search for difference and separateness (alterity) and the problem
      with the Other seen through the lens ofthe individuation process in adolescence.
      These are explored with reference to relational aspects and Levinas and Girard's
      divergent views of the Other. The relational space, which in Phillip Bromberg's
      (2003) words is 'uniquely relational, but still uniquely individual' and in which
      analyst and patient 'stand together in the space between realities', might under
      exceptional circumstances be transformed into 'a twilight space where the
      impossible becomes possible' (p. 573). I will sketch a developmental trajectory
      starting from primitive states, in which the presence of the Other,as a separate
      entity cannot be tolerated and where the patient strives for total mimesis.
      Should the analyst prematurely shatter this illusion, she becomes an alien
      'Other'; a wolf in sheep's clothing. I trace the current psychoanalytic paradigm
      shift to an emphasis on the co-creation of meaning in the interpersonal space and
      explore what alterity consists of and how much of the other's unknowability can
      be tolerated and respected without a translation into one's own idiom. The
      clinical vignettes illustrate aspects of therapy which normally lie outside the
      analytical remit and are culled from an inpatient setting and private practice.

PMID- 24673276
TI  - Jung's understanding of schizophrenia: is it still relevant in the 'era of the
      brain'?
AB  - Jung was highly committed to grasping the meaning of psychotic thinking, and left
      behind precious insights to treatment scattered through his works written between
      1906 and 1958. The tendency of today's psychiatry is to attribute the psychotic
      process to alteration in the brain's anatomy, biochemistry and electrophysiology,
      thus exempting the subject, i.e. the afflicted person, from responsibility for
      attachment to reality and their sanity. Jung understood schizophrenia as an
      'abaissement du niveau mental', a similar phenomenon to the one encountered in
      dreams, and caused by a peculiar 'faiblesse de la volonte'. He contested that
      complexes in schizophrenia, in contrast with neurotic disorders, are disconnected
      and can either never reintegrate to the psychic totality or can only join
      together in remission 'like a mirror broke into splinters' (Jung , para. 507).
      Accordingly, a person who does not fight for the supremacy of ego consciousness
      and has let themself be swayed by the intrusion of alien contents arising from
      the unconscious (even to the point of becoming fascinated by regression) is
      exposed to the danger of schizophrenia. The contemporary relevance of these
      notions and their necessity in understanding the psychotic process in the light
      of modern scientific findings are discussed. 

PMID- 24673277
TI  - Jung's evolving views of Nazi Germany: from 1936 to the end of World War II.
AB  - This article first shows Jung's evolving views of Nazi Germany from 1936 to the
      beginning of World War II. In a lecture at the Tavistock Clinic, London, in
      October 1936, he made his strongest and most negative statements to that date
      about Nazi Germany. While in Berlin in September 1937 for lectures to the Jung
      Gesellschaft, his observations of Hitler at a military parade led him to conclude
      that should the catastrophe of war come it would be far more and bloodier than he
      had previously supposed. After the Sudetenland Crisis in Fall 1938, Jung in
      interviews made stronger comments on Hitler and Nazi Germany. The article shows
      how strongly anti-Nazi Jung's views were in relation to events during World War
      II such as Nazi Germany's invasion of Poland, the fall of France, the bombings of
      Britain, the U.S. entry into the War, and Allied troops advancing into Germany.
      Schoenl and Peck, 'An Answer to the Question: Was Jung, for a Time, a "Nazi
      Sympathizer" or Not?' (2012) demonstrated how his views of Nazi Germany changed
      from 1933 to March 1936. The present article shows how his views evolved from
      1936 to the War's end in 1945. 

PMID- 24673278
TI  - Jung's views on causes and treatments of schizophrenia in light of current trends
      in cognitive neuroscience and psychotherapy research II: psychological research
      and treatment.
AB  - Jung was the first to emphasize the importance of psychological factors in the
      aetiology and treatment of schizophrenia. Despite this, and other seminal
      contributions, his work on schizophrenia is almost completely ignored or
      forgotten today. This paper, a follow-up to one on Jung's theories of aetiology
      and symptom formation in schizophrenia (Journal of Analytical Psychology, 59, 1)
      reviews Jung's views on psychological approaches to research on, and treatment
      of, the disorder. Five themes are covered: 1) experimental psychopathology; 2)
      attentional disturbance; 3) psychological treatment; 4) the relationship between
      the environment (including the psychiatric hospital) and symptom expression; and
      5) heterogeneity and the schizophrenia spectrum. Review of these areas reveal
      that Jung's ideas about the kind of research that can elucidate psychological
      mechanisms in schizophrenia, and the importance of psychotherapy for people with
      this condition, are very much in line with contemporary paradigms. Moreover,
      further exploration of several points of convergence could lead to advances in
      both of these fields, as well as within analytical psychology. 

PMID- 24673282
TI  - The science and policy of critical loads of pollutant deposition to protect
      ecosystems in New York.
AB  - We discuss the potential for adopting a critical load (CL) of air pollutant
      deposition approach to inform natural resource protection and management in New
      York. The CL reflects the quantitative exposure to pollutants below which
      significant harmful effects on specified sensitive elements of the environment do
      not occur. Here, we discuss how CLs can be used to protect sensitive ecosystems
      against the harmful effects of atmospheric sulfur and nitrogen deposition and
      associated soil and water acidification and nutrient enrichment. The CL can be
      used diagnostically to determine resources at risk and prescriptively to evaluate
      the effectiveness of regulations and to manage resources. 

PMID- 24673283
TI  - Measurement of nanomaterials in foods: integrative consideration of challenges
      and future prospects.
AB  - The risks and benefits of nanomaterials in foods and food contact materials
      receive conflicting international attention across expert stakeholder groups as
      well as in news media coverage and published research. Current nanomaterial
      characterization is complicated by the lack of accepted approaches to measure
      exposure-relevant occurrences of suspected nanomaterials in food and by broad
      definitions related to food processing and additive materials. Therefore, to
      improve understanding of risk and benefit, analytical methods are needed to
      identify what materials, new or traditional, are "nanorelevant" with respect to
      biological interaction and/or uptake during alimentary tract transit. Challenges
      to method development in this arena include heterogeneity in nanomaterial
      composition and morphology, food matrix complexity, alimentary tract diversity,
      and analytical method limitations. Clear problem formulation is required to
      overcome these and other challenges and to improve understanding of biological
      fate in facilitating the assessment of nanomaterial safety or benefit, including
      sampling strategies relevant to food production/consumption and alimentary tract
      transit. In this Perspective, we discuss critical knowledge gaps that must be
      addressed so that measurement methods can better inform risk management and
      public policy. 

PMID- 24673284
TI  - A review of ergostane and cucurbitane triterpenoids of mushroom origin.
AB  - Ergostane and cucurbitane triterpenoids are relatively rare in mushroom
      metabolites, and a total of 55 compounds are reported up to May 2013. Many of
      them exhibited diverse biological properties such as anti-inflammatory, cytotoxic
      and antioxidative activities. The paper reviewed systematically the isolation,
      structure elucidation and biological activities of ergostane- and cucurbitane
      type triterpenoids from mushroom for the first time. 

PMID- 24673285
TI  - High-frequency p16(INK) (4A) promoter methylation is associated with histone
      methyltransferase SETDB1 expression in sporadic cutaneous melanoma.
AB  - Epigenetic mechanisms participate in melanoma development and progression. The
      effect of histone modifications and their catalysing enzymes over euchromatic
      promoter DNA methylation in melanoma remains unclear. This study investigated the
      potential association of p16(INK) (4A) promoter methylation with histone
      methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and
      their correlation with clinicopathological characteristics. Promoter methylation
      was detected by methylation-specific PCR in 100 peripheral blood samples and 58
      melanoma tissues from the same patients. Cell proliferation (Ki-67 index),
      p16(INK) (4A) and SETDB1 expression were evaluated by immunohistochemistry. High
      frequency promoter methylation (25.86%) was observed in tissue samples and
      correlated with increased cell proliferation (P = 0.0514). p16(INK) (4A) promoter
      methylation was higher in vertical growth-phase (60%) melanomas than in radial
      (40%, P = 0.063) and those displaying epidermal involvement (P = 0.046).
      Importantly, p16(INK) (4A) methylation correlated with increased melanoma
      thickness according to Breslow index (P = 0.0495) and marginally with increased
      Clark level (I/II vs III/IV/V, P = 0.070). Low (1-30%) p16(INK) (4A) expression
      was detected at the majority (19 of 54) of melanoma cases (35.19%), being
      marginally correlated with tumor lymphocytic infiltration (P = 0.078). SETDB1
      nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of
      57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression
      correlated with higher frequency of p16(INK) (4A) methylation and p16(INK) (4A)
      expression (P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels
      were associated with higher mitotic count (0-5/mm(2) vs >5/mm(2) , P = 0.0869),
      advanced Clark level (III-V, P = 0.0380), epidermal involvement (P = 0.0331) and
      the non-chronic sun exposure-associated melanoma type (P = 0.0664). Our data
      demonstrate for the first time the association of histone methyltransferase
      SETDB1 with frequent methylation of the euchromatic p16(INK) (4A) promoter and
      several prognostic parameters in melanomas. 

PMID- 24673288
TI  - Locally induced and self-induced "electroclick" onto a self-assembled monolayer:
      writing and reading with SECM under unbiased conditions.
AB  - Localized "electroclick" was achieved on azido-terminated self-assembled
      monolayers using Scanning Electrochemical Microscopy (SECM) in feedback mode, in
      which the substrate is not electrically connected (unbiased conditions). The
      method allows both the local immobilization of diverse functional moieties and
      the monitoring of each modification step at a micrometer scale. Conditions of the
      "click" coupling reaction were optimized especially to avoid the deposit of
      metallic copper by the choice of a specific ligand to stabilize the Cu(I)
      species. The catalytic efficiency in localized "electroclick" reaction of
      Cu(II)TMPA (TMPA: tris(2-pyridylmethyl)amine) as the "click" catalyst was
      compared with a derivative containing an alkyne group Cu(II)6eTMPA, the same
      molecule playing the role of the catalyst and the substrate. Evidences for
      surface self-catalysis propagation are demonstrated through SECM imaging showing
      a random 2D progression of the catalytic modification. 

PMID- 24673287
TI  - The genetic potential for key biogeochemical processes in Arctic frost flowers
      and young sea ice revealed by metagenomic analysis.
AB  - Newly formed sea ice is a vast and biogeochemically active environment. Recently,
      we reported an unusual microbial community dominated by members of the
      Rhizobiales in frost flowers at the surface of Arctic young sea ice based on the
      presence of 16S gene sequences related to these strains. Here, we use metagenomic
      analysis of two samples, from a field of frost flowers and the underlying young
      sea ice, to explore the metabolic potential of this surface ice community. The
      analysis links genes for key biogeochemical processes to the Rhizobiales,
      including dimethylsulfide uptake, betaine glycine turnover, and halocarbon
      production. Nodulation and nitrogen fixation genes characteristic of terrestrial
      root-nodulating Rhizobiales were generally lacking from these metagenomes. Non
      Rhizobiales clades at the ice surface had genes that would enable additional
      biogeochemical processes, including mercury reduction and
      dimethylsulfoniopropionate catabolism. Although the ultimate source of the
      observed microbial community is not known, considerations of the possible role of
      eolian deposition or transport with particles entrained during ice formation
      favor a suspended particle source for this microbial community. 

PMID- 24673286
TI  - PdO doping tunes band-gap energy levels as well as oxidative stress responses to
      a Co3O4 p-type semiconductor in cells and the lung.
AB  - We demonstrate through PdO doping that creation of heterojunctions on Co3O4
      nanoparticles can quantitatively adjust band-gap and Fermi energy levels to study
      the impact of metal oxide nanoparticle semiconductor properties on cellular redox
      homeostasis and hazard potential. Flame spray pyrolysis (FSP) was used to
      synthesize a nanoparticle library in which the gradual increase in the PdO
      content (0-8.9%) allowed electron transfer from Co3O4 to PdO to align Fermi
      energy levels across the heterojunctions. This alignment was accompanied by free
      hole accumulation at the Co3O4 interface and production of hydroxyl radicals.
      Interestingly, there was no concomitant superoxide generation, which could
      reflect the hole dominance of a p-type semiconductor. Although the electron flux
      across the heterojunctions induced upward band bending, the E(c) levels of the
      doped particles showed energy overlap with the biological redox potential (BRP).
      This allows electron capture from the redox couples that maintain the BRP from 
      4.12 to -4.84 eV, causing disruption of cellular redox homeostasis and induction
      of oxidative stress. PdO/Co3O4 nanoparticles showed significant increases in
      cytotoxicity at 25, 50, 100, and 200 MUg/mL, which was enhanced incrementally by
      PdO doping in BEAS-2B and RAW 264.7 cells. Oxidative stress presented as a tiered
      cellular response involving superoxide generation, glutathione depletion,
      cytokine production, and cytotoxicity in epithelial and macrophage cell lines. A
      progressive series of acute pro-inflammatory effects could also be seen in the
      lungs of animals exposed to incremental PdO-doped particles. All considered,
      generation of a combinatorial PdO/Co3O4 nanoparticle library with incremental
      heterojunction density allowed us to demonstrate the integrated role of E(v),
      E(c), and E(f) levels in the generation of oxidant injury and inflammation by the
      p-type semiconductor, Co3O4.

PMID- 24673289
TI  - The prevalence of hidradenitis suppurativa in 1093 patients with inflammatory
      bowel disease.

PMID- 24673290
TI  - Outcome of patients with serology suggestive of past hepatitis B virus infection
      during antitumor necrosis factor therapy for psoriasis.
AB  - BACKGROUND: Recently, the reactivation during treatment with tumor necrosis
      factor (TNF) blockers has exceptionally been described in patients with hepatitis
      B virus (HBV) antigen-negative (HBsAg). The objective was to evaluate the
      influence of anti-TNF agents in patients with psoriasis and serology suggesting
      past hepatitis B state. METHODS: The inclusion criteria were chronic plaque
      psoriasis treated with anti-TNF therapy, HBsAg-negative, and HBcAb-positive. We
      gathered the demographic data and type and duration of anti-TNF agent. Serum
      aminotransferase levels and HBV serologic status were requested at baseline and
      during follow-up. RESULTS: We have included 13 patients (four women, nine men)
      (mean age of 62.1 years). The agent was etanercept in seven cases, infliximab in
      four patients, and adalimumab in the other two. The mean duration of TNF therapy
      was 28.6 months. None of them became HBsAg-positive. Neither signs nor symptoms
      of acute hepatitis were reported. CONCLUSION: The management of HBsAg-negative
      patients is unresolved. Only nine cases of HBV reactivation during treatment with
      TNF blockers have been reported. Despite the low risk of reactivation in these
      patients, we recommend the monitoring of serum aminotransferase levels, HBsAb
      titers, HBsAg and, if possible, viral load.

PMID- 24673292
TI  - Dehalogenimonas lykanthroporepellens BL-DC-9T simultaneously transcribes many
      rdhA genes during organohalide respiration with 1,2-DCA, 1,2-DCP, and 1,2,3-TCP
      as electron acceptors.
AB  - The genome sequence of the organohalide-respiring bacterium Dehalogenimonas
      lykanthroporepellensBL-DC-9(T) contains numerous loci annotated as reductive
      dehalogenase homologous (rdh) genes based on inferred protein sequence identity
      with functional dehalogenases of other bacterial species. Many of these genes are
      truncated, lack adjacent regulatory elements, or lack cognate genes coding for
      membrane-anchoring proteins typical of the functionally characterized active
      reductive dehalogenases of organohalide-respiring bacteria. To investigate the
      expression patterns of the rdh genes in D. lykanthroporepellensBL-DC-9(T),
      oligonucleotide primers were designed to uniquely target 25 rdh genes present in
      the genome as well as four putative regulatory genes. RNA extracts from cultures
      of strain BL-DC-9(T) actively dechlorinating three different electron acceptors,
      1,2-dichloroethane, 1,2-dichloropropane, and 1,2,3-trichloropropane were reverse
      transcribed and subjected to PCR amplification using rdh-specific primers.
      Nineteen rdh gene transcripts, including 13 full-length rdhA genes, six truncated
      rdhA genes, and five rdhA genes having cognate rdhB genes were consistently
      detected during the dechlorination of all three of the polychlorinated alkanes
      tested. Transcripts from all four of the putative regulatory genes were also
      consistently detected. Results reported here expand the diversity of bacteria
      known to simultaneously transcribe multiple rdh genes and provide insights into
      the transcription factors associated with rdh gene expression.

PMID- 24673293
TI  - Time with peers from middle childhood to late adolescence: developmental course
      and adjustment correlates.
AB  - This study examined the developmental course and adjustment correlates of time
      with peers from age 8 to 18. On seven occasions over 8 years, the two eldest
      siblings from 201 European American, working- and middle-class families provided
      questionnaire and/or phone diary data. Multilevel models revealed that girls'
      time with mixed-/opposite-sex peers increased beginning in middle childhood, but
      boys' time increased beginning in early adolescence. For both girls and boys,
      time with same-sex peers peaked in middle adolescence. At the within-person
      level, unsupervised time with mixed-/opposite-sex peers longitudinally predicted
      problem behaviors and depressive symptoms, and supervised time with mixed
      /opposite-sex peers longitudinally predicted better school performance. Findings
      highlight the importance of social context in understanding peer involvement and
      its implications for youth development. 

PMID- 24673291
TI  - Animal models of sports-related head injury: bridging the gap between pre
      clinical research and clinical reality.
AB  - Sports-related head impact and injury has become a very highly contentious public
      health and medico-legal issue. Near-daily news accounts describe the travails of
      concussed athletes as they struggle with depression, sleep disorders, mood
      swings, and cognitive problems. Some of these individuals have developed chronic
      traumatic encephalopathy, a progressive and debilitating neurodegenerative
      disorder. Animal models have always been an integral part of the study of
      traumatic brain injury in humans but, historically, they have concentrated on
      acute, severe brain injuries. This review will describe a small number of new and
      emerging animal models of sports-related head injury that have the potential to
      increase our understanding of how multiple mild head impacts, starting in
      adolescence, can have serious psychiatric, cognitive and histopathological
      outcomes much later in life. Sports-related head injury (SRHI) has emerged as a
      significant public health issue as athletes can develop psychiatric and
      neurodegenerative disorders later in life. Animal models have always been an
      integral part of the study of human TBI but few existing methods are valid for
      studying SRHI. In this review, we propose criteria for effective animal models of
      SRHI. Movement of the head upon impact is judged to be of primary importance in
      leading to concussion and persistent CNS dysfunction. 

PMID- 24673294
TI  - Analysis of genetic association and epistasis interactions between circadian
      clock genes and symptom dimensions of bipolar affective disorder.
AB  - Bipolar affective disorder (BD) is a severe psychiatric disorder characterized by
      periodic changes in mood from depression to mania. Disruptions of biological
      rhythms increase risk of mood disorders. Because clinical representation of
      disease is heterogeneous, homogenous sets of patients are suggested to use in the
      association analyses. In our study, we aimed to apply previously computed
      structure of bipolar disorder symptom dimension for analyses of genetic
      association. We based quantitative trait on: main depression, sleep disturbances,
      appetite disturbances, excitement and psychotic dimensions consisted of OPCRIT
      checklist items. We genotyped 42 polymorphisms from circadian clock genes: PER3,
      ARNTL, CLOCK and TIMELSSS from 511 patients BD (n = 292 women and n = 219 men).
      As quantitative trait we used clinical dimensions, described above. Genetic
      associations between alleles and quantitative trait were performed using applied
      regression models applied in PLINK. In addition, we used the Kruskal-Wallis test
      to look for associations between genotypes and quantitative trait. During second
      stage of our analyses, we used multidimensional scaling (multifactor
      dimensionality reduction) for quantitative trait to compute pairwise epistatic
      interactions between circadian gene variants. We found association between ARNTL
      variant rs11022778 main depression (p = 0.00047) and appetite disturbances (p =
      0.004). In epistatic interaction analyses, we observed two locus interactions
      between sleep disturbances (p = 0.007; rs11824092 of ARNTL and rs11932595 of
      CLOCK) as well as interactions of subdimension in main depression and ARNTL
      variants (p = 0.0011; rs3789327, rs10766075) and appetite disturbances in
      depression and ARNTL polymorphism (p = 7 * 10(-4); rs11022778, rs156243).

PMID- 24673295
TI  - The influence of women's attachment style on the chronobiology of labour pain,
      analgesic consumption and pharmacological effect.
AB  - Circadian variation in biological rhythms has been identified as affecting both
      labour pain and the pharmacological properties of analgesics. In the context of
      pain, there is also a growing body of evidence suggesting the importance of adult
      attachment. The purpose of this study was to examine whether labour pain,
      analgesic consumption and pharmacological effect are significantly affected by
      the time of day and to analyse whether this circadian variation is influenced by
      women's attachment style. This prospective observational study included a sample
      of 81 pregnant women receiving patient-controlled epidural analgesia (PCEA).
      Attachment was assessed with the Adult Attachment Scale - Revised. The perceived
      intensity of labour pain in the early stage of labour (3 cm of cervical
      dilatation and before the administration of PCEA) was measured using a visual
      analogue scale (VAS). Pain was also indirectly assessed by measuring the
      consumption of anaesthetics. The latency period and the duration of effect were
      recorded for a chronopharmacology characterisation. Pain, as assessed with the
      VAS, was significantly higher in the night-time group than in the daytime group.
      An insecure attachment style was significantly associated with greater labour
      pain at 3 cm of cervical dilatation (p < 0.001) and before the beginning of
      analgesia (p < 0.001) as well as with higher analgesic consumption and lower
      pharmacological efficacy (p < 0.05). The time of day was significantly associated
      with the pharmacological effect: the latency period was longer at night, and the
      duration of the pharmacological effect was longer during the daytime. The
      interaction between time of day and attachment style was not significant for any
      of the study variables. Our results provide evidence of the importance of
      circadian variation in studying labour pain and the pharmacological effect of
      labour analgesia involving epidural blockage with a PCEA regimen. Moreover,
      although there was no evidence that attachment style influenced the circadian
      variation, these data emphasise that insecure attachment patterns are a risk
      factor for greater labour pain and analgesic consumption, which should be
      considered in pain management approaches.

PMID- 24673296
TI  - Association between light exposure at night and nighttime blood pressure in the
      elderly independent of nocturnal urinary melatonin excretion.
AB  - Circadian misalignment between internal and environmental rhythms dysregulates
      blood pressure (BP) variability because of disruption of the biological clock,
      resulting in increased nighttime BP. Although exposure to light-at-night is
      associated with the circadian misalignment, it remains unclear whether exposure
      to light-at-night in home settings is associated with nighttime BP. In this cross
      sectional analysis of 528 elderly individuals (mean age: 72.8 years), we measured
      bedroom light intensity at 1-min intervals on two consecutive nights along with
      ambulatory BP, overnight urinary melatonin excretion and actigraphy. With regard
      to adjusted mean comparisons using analysis of covariance, the light-at-night
      group (average: >=5 lux; n = 109) showed significantly higher nighttime systolic
      BP (SBP; adjusted mean: 120.8 vs. 116.5 mmHg, p = 0.01) and diastolic BP (70.1
      vs. 67.1 mmHg, p < 0.01) compared with the Darker group (average: <5 lux; n =
      419) independently of potential confounding factors including overnight urinary
      melatonin excretion and actigraphic sleep quality. We observed consistent
      associations between light-at-night and nighttime BP in different cutoff values
      for light-at-night intensity (i.e. 3 and 10 lux). In conclusion, exposure to
      light-at-night in home settings is significantly associated with increased
      nighttime BP in elderly individuals independently of overnight urinary melatonin
      excretion. A 4.3 mmHg increase in nighttime SBP is associated with a 6.1%
      increase in total mortality, which corresponds to approximately 10 000 annual
      excess deaths in Japanese elderly population.

PMID- 24673298
TI  - Association of endothelial nitric oxide synthase gene polymorphisms with end
      stage renal disease: a systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Endothelial nitric oxide synthase (eNOS) is one of the
      potent regulators of intra renal hemodynamics. Polymorphisms of eNOS gene may be
      involved in the progression of renal disease, and may be the causative factors
      that contribute to the deterioration of renal functions. During the past decades,
      several studies investigated the association of eNOS polymorphisms with the risk
      of end-stage renal disease (ESRD), but the results remain unclear and the
      mechanisms are not defined. Our study was designed to examine the role of
      different eNOS genetic polymorphisms in the progression of ESRD. MATERIALS AND
      METHODS: Relevant studies were identified through PubMed, Embase, Medline and
      CNKI (China National Knowledge Infrastructure) database published between January
      2000 and November 2013. The association between eNOS polymorphisms and ESRD
      susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence
      intervals (95% CI) in fixed or random effects models. RESULTS: Sixteen articles
      were identified for the analysis of association between eNOS gene polymorphisms
      and ESRD risk. A total of 2729 patients and 2190 controls for 4b/a, 851 patients
      and 1171 controls for G894T, and 513 patients and 487 controls for T786C were
      included in our analysis. Overall, 4a allele of 4b/a polymorphism produced a
      significant association in the global population (OR = 1.47, 95% CI = 1.05-2.06,
      p = 0.03) in a random-effect model; T allele of G894T was also significantly
      associated with ESRD susceptibility in overall populations (OR = 2.12, 95% CI =
      1.44-3.12, p = 0.0001). Furthermore, 4a and T carriers were significantly
      associated with ESRD risk as well. No association was found between T786C
      polymorphism and ESRD. CONCLUSION: The evidence accumulated suggested that 4b/a
      and G894T polymorphisms in the eNOS gene were associated with ESRD
      susceptibility, indicating that 4a and T allele carriers might become significant
      genetic molecular markers for the onset of ESRD in overall populations. However,
      more studies should be performed in the further studies.

PMID- 24673297
TI  - A longitudinal study of Babesia microti infection in seropositive blood donors.
AB  - BACKGROUND: Babesia infection is caused by intraerythrocytic tick-borne
      parasites. Cases of transfusion-transmitted babesiosis have been increasingly
      recognized. To date, no Babesia test has been licensed for screening US blood
      donors. We conducted a longitudinal study to assess the course and markers of
      Babesia infection among seropositive donors identified in a seroprevalence study.
      STUDY DESIGN AND METHODS: Eligible donors had B. microti indirect fluorescent
      antibody (IFA) titers of 64 or greater. Enrollees were monitored up to 3 years,
      by IFA and three methods for evidence of parasitemia: B. microti nested
      polymerase chain reaction (PCR) analysis (at two laboratories), hamster
      inoculation, and blood-smear examination. RESULTS: Among 115 eligible donors, 84
      (73%) enrolled. Eighteen enrollees (21%) had evidence of parasitemia for 30 total
      specimens (17% of 181), which were collected in 9 different months and tested
      positive by various approaches: PCR (25 specimens/16 persons), hamster
      inoculation (13 specimens/8 persons), and blood smear (one specimen positive by
      all three approaches). Overall, 14 persons had one or more specimen with positive
      PCR results at both laboratories (12 persons) and/or had parasitologically
      confirmed infection (eight persons). Three of nine persons who had more than one
      specimen with evidence of parasitemia had nonconsecutive positives. Several
      enrollees likely had been infected at least 1 year when their last positive
      specimen was collected. The final three specimens for seven persons tested
      negative by all study methods, including IFA. CONCLUSION: Seropositive blood
      donors can have protracted low-level parasitemia that is variably and
      intermittently detected by parasitologic and molecular methods. Donor-screening
      algorithms should include serologic testing and not solely rely on molecular
      testing.

PMID- 24673299
TI  - A contact-based intervention for people recently discharged from inpatient
      psychiatric care: a pilot study.
AB  - People recently discharged from inpatient psychiatric care are at high risk of
      suicide and self-harm, with 6% of all suicides in England occurring in the 3
      months after discharge. There is some evidence from a randomized trial carried
      out in the United States in the 1960s-70s that supportive letters sent by
      psychiatrists to high-risk patients in the period following hospital discharge
      resulted in a reduction in suicide. The aim of the current pilot study was to
      assess the feasibility of conducting a similar trial, but in a broader group of
      psychiatric discharges, in the context of present day UK clinical practice. The
      intervention was piloted on 3 psychiatric inpatient wards in southwest England.
      On 2 wards a series of 8 letters were sent to patients over the 12 months after
      discharge and 6 letters were sent from the third ward over a 6 month period. A
      total of 102 patients discharged from the wards received at least 1 letter, but
      only 45 (44.1%) received the full series of letters. The main reasons for drop
      out were patient opt-out (n = 24) or readmission (n = 26). In the context of a
      policy of intensive follow-up post-discharge, qualitative interviews with service
      users showed that most already felt adequately supported and the intervention
      added little to this. Those interviewed felt that it was possible that the
      intervention might benefit people new to or with little follow-up from mental
      health services but that fewer letters should be mailed. 

PMID- 24673300
TI  - Hydroxide-free cubane-shaped tetranuclear [Ln4] complexes.
AB  - The reaction of the lanthanide(III) chloride salts [Gd(III), Tb(III), and
      Dy(III)] with a new chelating, flexible, and sterically unencumbered multisite
      coordinating compartmental Schiff-base ligand (E)-2-((6-(hydroxymethyl)pyridin-2
      yl)methyleneamino)phenol (LH2) and pivalic acid (PivH) in the presence of
      triethylamine (Et3N) affords a series of tetranuclear Ln(III) coordination
      compounds, [Ln4(L)4(MU2-eta(1)eta(1)Piv)4].xH2O.yCH3OH (1, Ln = Gd(III), x = 3, y
      = 6; 2, Ln = Tb(III), x = 6, y = 2; 3, Ln = Dy(III), x = 4, y = 6). X-ray
      diffraction studies reveal that the molecular structure contains a distorted
      cubane-like [Ln4(MU3-OR)4](+8) core, which is formed by the concerted
      coordination action of four dianionic L(2-) Schiff-base ligands. Each lanthanide
      ion is eight-coordinated (2N, 6O) to form a distorted-triangular dodecahedral
      geometry. Alternating current susceptibility measurements of complex 3 reveal
      frequency- and temperature-dependent two-step out-of-phase signals under zero
      direct current (dc) field, which is characteristic of single-molecule magnet
      behavior. Analysis of the dynamic magnetic data under an applied dc field of 1000
      Oe to fully or partly suppress the quantum tunneling of magnetization relaxation
      process affords the anisotropic barriers and pre-exponential factors: Delta/kB =
      73(2) K, tau0 = 4.4 * 10(-8) s; Delta/kB = 47.2(9) K, tau0 = 5.0 * 10(-7) s for
      the slow and fast relaxations, respectively. 

PMID- 24673301
TI  - BH3-only proteins: possible proapoptotic triggers for melanoma therapy.
AB  - Despite recent developments for new targeted therapies in melanoma, as BRAF
      inhibitors and immune-stimulating antibodies, tumor relapse frequently follows
      within less than a year. Therapy resistance is explained by defects in
      proapoptotic signalling. Thus, efficient induction of apoptosis in tumor cells
      appears as predominant therapeutic goal. In apoptosis control of melanoma, the
      balance between pro- and antiapoptotic Bcl-2 proteins plays a decisive role. In
      particular, members of the subfamily of BH3-only proteins function as
      proapoptotic triggers, and mimetics of these proteins are already in clinical
      trials in other cancers. Recent experimental work has revealed that the effects
      of different treatments in melanoma are related to the activation of BH3-only
      proteins, and also the proapoptotic effects of BRAF inhibitors are prevented by
      knockdown of the BH3-only protein Bim. Thus, melanoma therapy might be critically
      improved by the combination of survival pathway antagonists as BRAF inhibitors
      with BH3 mimetics.

PMID- 24673302
TI  - Sunscreen photopatch testing: a series of 157 children.
AB  - BACKGROUND: Photoprotection including sunscreen use in children is encouraged by
      health campaigns. While sunscreen chemicals are common causes of photoallergic
      (PA) contact reactions in adults, limited data are available in children.
      OBJECTIVES: To assess the frequency of PA and contact allergy (CA) to sunscreens
      in children aged < 18 years undergoing investigation for suspected
      photosensitivity. METHODS: Retrospective analysis of data on children who
      underwent photopatch testing to a standard series of nine ultraviolet (UV)
      filters and to sunscreen products in a single photoinvestigation centre (2000
      11). Duplicate series of UV filters and the children's own sunscreen products
      were applied to the back, with readings taken at sample removal, and at 24 and 48
      h after 5 J cm(-2) UVA exposure of one series. RESULTS: The analysis comprised
      157 children (aged 3-17 years, 69 male and 88 female). In total 10 children
      (6.4%) showed positive photopatch responses to UV filters and/or their sunscreen
      products (4.5% to UV filters, 5.7% to their sunscreen products). The responsible
      UV filters most often identified were benzophenone-3 and octyl methoxycinnamate.
      Additionally, CA reactions were observed in nine children (5.7%), with 16
      children (10.2%) showing PA and/or CA to UV filters and/or sunscreen products.
      CONCLUSIONS: This is the largest series of photopatch testing reported in
      children, and shows that both sunscreen PA and CA are quite frequent in those
      undergoing photoinvestigation. Photopatch testing should be considered in
      children presenting with features of photosensitivity.

PMID- 24673303
TI  - Inflammatory bowel disease: healthcare costs for patients who are adherent or non
      adherent with infliximab therapy.
AB  - OBJECTIVE: Healthcare costs of inflammatory bowel disease are substantial. This
      study examined the effect of adherence versus non-adherence on healthcare costs
      in patients with inflammatory bowel disease. METHODS: Adults who started
      infliximab treatment between 2006 and 2009 and had a diagnosis of inflammatory
      bowel disease were identified from MarketScan Databases. Medication adherence was
      defined as an infliximab medication possession ratio of 80% or greater in the
      first year. Mean treatment effects (adherence versus non-adherence) on costs in
      adherent patients were estimated with propensity-weighted generalized linear
      models. RESULTS: A total of 1646 patients were identified. Significant variables
      in the model used to develop propensity weights were age, year of infliximab
      initiation, having Medicare coverage, presence of supplementary diagnoses, office
      as the place of service for infliximab initiation, prior aminosalicylate use,
      prior outpatient costs, number of prior outpatient visits, and number of prior
      colonoscopies. Mean total costs in adherent (n = 674) and propensity-weighted non
      adherent (n = 972) patients were $41,713 versus $47,411 overall (p < 0.001),
      including $28,289 versus $14,889 for infliximab drug costs (p < 0.001), $2458
      versus $17,634 for hospitalizations (p < 0.001), $7357 versus $10,909 for
      outpatient visits (p < 0.001), $236 versus $458 for emergency room visits (p <
      0.001), and $3373 versus $3521 for other pharmaceuticals costs (p = 0.460).
      LIMITATIONS: Costs associated with infliximab administration (infusions, adverse
      events) were captured in healthcare costs (inpatient, outpatient, and emergency
      room), not in infliximab costs. The influence of adherence on indirect costs
      (e.g., time lost from work) could not be determined. Reasons for non-adherence
      were not available in the database. CONCLUSIONS: In patients who were adherent to
      infliximab treatment (a medication possession ratio of 80% or greater in the
      first year), adherence versus non-adherence was associated with lower total
      healthcare costs, supporting the overall value of infliximab adherence in
      patients with inflammatory bowel disease.

PMID- 24673304
TI  - Boredom is the enemy.

PMID- 24673312
TI  - Dementia strategy now needs updating to build on success.

PMID- 24673313
TI  - Exercise stays central to treatment of osteoarthritis in latest advice.

PMID- 24673317
TI  - Please listen to carers' views about stroke services.

PMID- 24673318
TI  - Would you be able to spot a foot attack?

PMID- 24673322
TI  - Practice question.

PMID- 24673323
TI  - Why intermediate care services need to be refreshed.
AB  - Intermediate care services are usually intended for frail, older people and those
      with complex needs. Their aims are to avoid unnecessary hospital admission, help
      people regain independence after a hospital stay and prevent premature admission
      to long-term care. Services are time limited and delivered in patients' own
      homes, community hospitals and sometimes nursing homes. But, as Louise Hunt
      reports, the second national audit of intermediate care, published late last
      year, found capacity in England is just half of what is needed. There is also
      significant variation between localities in capacity outside hospital and in the
      balance of bed-based, home-based and re-enablement services. Two case studies are
      presented of intermediate care services where nurses play an important role in
      achieving positive outcomes for patients and saving the health service money. 

PMID- 24673324
TI  - Leg clubs: a runaway success.
AB  - The Barnstaple Leg Club has been running for almost two years in north Devon
      providing treatment and support to older people with leg ulcers on a weekly
      basis. This article examines the concept of leg clubs and describes how the
      community nursing team that leads the club offers holistic care to local people.
      The nurses are able to see more patients than they would by carrying out home
      visits, healing their wounds and boosting their self-esteem and confidence, while
      at the same time reducing social isolation. 

PMID- 24673325
TI  - Association between quality of life and religious coping in older people.
AB  - AIM: To examine the association between quality of life (QoL) and religious
      coping in older people living in their own homes. METHOD: A descriptive
      analytical study was undertaken in Iran with 200 older people aged over 60 living
      in their own homes who were selected for inclusion by systematic random sampling.
      Data were collected by use of the Short Form 36 (SF-36) QoL questionnaire and a
      religious coping questionnaire developed previously by the authors. RESULTS:
      There was no significant association between QoL and religious coping. However,
      mental health (r=0.20, P=0.003) and social function (r=0.20, P=0.004) had a
      significant association with the total score for religious coping. An association
      between a high level of religious coping and QoL was significant only for the
      mental health domain of the SF-36 (P=0.04). CONCLUSION: In light of these
      results, it can be suggested that older people's mental health and social
      function may be improved by strengthening their religious beliefs. Mental health
      and social function are associated with other QoL domains and so their promotion
      may also improve overall QoL.

PMID- 24673326
TI  - Effects of dog-assisted intervention on behavioural and psychological symptoms of
      dementia.
AB  - AIM: To evaluate the effect of a dog-assisted intervention on the behavioural and
      psychological symptoms of residents with dementia during a six-month period.
      METHOD: The study was conducted in eight nursing homes in Sweden. A total of 33
      residents with dementia, 20 in the intervention group and 13 in the control
      group, were recruited. The Cohen-Mansfield Agitation Inventory (CMAI) and the
      Multi-Dimensional Dementia Assessment Scale (MDDAS) were used to assess the
      effects of a dog-assisted intervention on participants' behavioural and
      psychological symptoms. The intervention comprised ten sessions, lasting between
      45 and 60 minutes, once or twice a week. Descriptive statistics were used to
      analyse background data, comparisons between groups at baseline were performed
      using the Mann-Whitney U test, and the Wilcoxon rank sum test was used to test
      differences in groups over time. RESULTS: In the intervention group changes from
      baseline to follow up immediately after the intervention were not significant,
      possibly because of the small sample size. Some positive tendencies were
      observed: the CMAI mean score for physical non-aggressive behaviours decreased
      from 18.5 at baseline to 15.3 at follow up immediately after the intervention;
      lower scores indicate fewer symptoms. Mean and median MDDAS scores for
      behavioural symptoms decreased from 15.3 and 13.5 respectively at baseline to
      13.1 and 12.0 respectively at follow up immediately after the intervention; lower
      scores indicate fewer symptoms. The CMAI mean score for verbal agitation
      increased significantly (P=0.035) from 17.2 at baseline to 20.6 at follow up six
      months after the intervention. CONCLUSION: Dog-assisted intervention may provide
      an alternative or a complement to pharmacological treatments to reduce
      behavioural symptoms in people with dementia, but its value and place in care
      require further evaluation.

PMID- 24673327
TI  - The right strategy.

PMID- 24673328
TI  - Expression of Prox1, D2-40, and WT1 in spindle cell hemangioma.
AB  - BACKGROUND: Spindle cell hemangioma is a benign vascular proliferation that
      usually occurs on acral sites. A recent report showed focal positive staining of
      Prox1 in spindle cell hemangioma. METHODS: We performed an immunohistochemical
      study of spindle cell hemangioma with antibodies to CD31, D2-40, Prox1, smooth
      muscle actin (SMA) and Wilms tumor-1 (WT-1). RESULTS: The endothelial cells in
      spindle cell hemangioma were positive for CD31 and Prox1, focally positive for D2
      40 and negative for WT-1, whereas the myoid spindle cells around the endothelial
      cells were weakly positive for WT-1. CONCLUSION: Our results suggest that spindle
      cell hemangioma is a lymphatic malformation.

PMID- 24673329
TI  - Anion-based pH responsive ionic liquids: design, synthesis, and reversible self
      assembling structural changes in aqueous solution.
AB  - The creation of pH responsive materials that undergo morphological transitions
      between micelle and vesicle induced by solution pH change is of great importance
      for their potential application in drug delivery and biochemical engineering.
      Here, we have developed a series of 18 pH responsive ionic liquids composed of 1
      alkyl-3-methylimidazolium cation, [C(n)mim](+) (n = 4, 6, 8, 10, 12, 14), and
      different pH responsive anions such as potassium phthalic acid ([C6H4COOKCOO](
      )), sodium sulfosalicylic acid ([C6H3OHCOOSO3Na](-)), and sodium m
      carboxylbenzenesulfonate ([C6H4COOSO3Na](-)). The aggregation behavior and self
      assembly structures of the ILs in aqueous solution have been investigated by
      surface tension, dynamic light scattering, transmission electron microscopy,
      small-angle X-ray scattering, and nuclear magnetic resonance spectroscopy. It was
      found for the first time that single tail ionic liquids, [C(n)mim]X (n = 12 and
      14, X = [C6H4COOKCOO], [C6H3OHCOOSO3Na], and [C6H4COOSO3Na]) could form vesicles
      without any additives, and reversible transition was observed between spherical
      micelles and vesicles with the change of solution pH value. The transition in
      self-assembly structures is suggested to be driven by the variation in molecular
      structure and hydrophilicity/hydrophobicity of anions of the ILs.

PMID- 24673330
TI  - Paracetamol induced Stevens-Johnson syndrome--toxic epidermal necrolysis overlap
      syndrome.
AB  - BACKGROUND: Though any drug can be a potential cause of such hypersensitivity
      reactions, paracetamol, an over-the-counter drug used extensively as an analgesic
      and antipyretic agent, is considered to be relatively safe, with hepatotoxicity
      as a major adverse effect only in large doses. MATERIALS AND METHODS: We report
      an instance of a severe case of SJS-TEN overlap syndrome in a 12-year-old girl,
      induced by three over-the-counter doses of 500 mg of paracetamol taken at 8-hour
      intervals for fever. RESULTS AND DISCUSSION: Stevens-Johnson Syndrome and its
      severe variant toxic epidermal necrolysis (TEN) are idiosyncratic, delayed
      hypersensitivity inflammatory adverse drug reactions that are associated with
      increased morbidity and mortality. However, treatment with antibiotics and
      intravenous corticosteroids along with supportive therapy improved the course of
      the disorder. CONCLUSION: This case report addresses the fact that severe
      hypersensitivity reactions can occur with paracetamol, which can be potentially
      dangerous and life threatening. It is hence important for the clinicians to be
      alert to such severe hypersensitivity reactions even with drugs which are
      considered to be potentially safe such as paracetamol.

PMID- 24673331
TI  - The vitamin D receptor turns off chronically activated T cells.
AB  - T cell proliferation and T helper (TH ) cells that make IL-17 (TH 17 cells) and
      IFN-gamma (TH 1 cells) have been shown to be inhibited by 1,25(OH)2 D3 . Previous
      work has shown that immune-mediated diseases, where TH 1 and TH 17 cells are
      pathogenic, are ameliorated with 1,25(OH)2 D3 treatment. Paradoxically,
      infectious diseases that require TH 1 and TH 17 responses for host resistance are
      unaffected by 1,25(OH)2 D3 treatment. Resting T cells are not responsive to
      vitamin D because they do not express the vitamin D receptor (VDR) until late
      after activation. T cells activated following an infection help clear the
      infection, and since the antigen is eliminated, vitamin D is not needed to dampen
      the immune response. Conversely, in immune-mediated disease, there is chronic T
      cell activation, and in this scenario, vitamin D and 1,25(OH)2 D3 are critical
      for inhibiting T cell proliferation and cytokine production. Vitamin D is a late
      regulator of T cell function and acts to turn off T cells. This paper will review
      these data. 

PMID- 24673332
TI  - Analyzing site selectivity in Rh2(esp)2-catalyzed intermolecular C-H amination
      reactions.
AB  - Predicting site selectivity in C-H bond oxidation reactions involving heteroatom
      transfer is challenged by the small energetic differences between disparate bond
      types and the subtle interplay of steric and electronic effects that influence
      reactivity. Herein, the factors governing selective Rh2(esp)2-catalyzed C-H
      amination of isoamylbenzene derivatives are investigated, where modification to
      both the nitrogen source, a sulfamate ester, and substrate are shown to impact
      isomeric product ratios. Linear regression mathematical modeling is used to
      define a relationship that equates both IR stretching parameters and Hammett
      sigma(+) values to the differential free energy of benzylic versus tertiary C-H
      amination. This model has informed the development of a novel sulfamate ester,
      which affords the highest benzylic-to-tertiary site selectivity (9.5:1) observed
      for this system. 

PMID- 24673333
TI  - Subjective social status and intergroup attitudes among ethnic majority and
      minority children in Portugal.
AB  - A measure of subjective social status (SSS) was examined among high (White), and
      low (Black and Roma) ethnic status children in Portugal within a developmental
      design including 6-8-year-old and 9-12-year-old children. White children favoured
      their in-group over the Black and Roma out-groups on the SSS measure, social
      preferences and positive as well as negative trait attributions. Generally, the
      Black and Roma showed equal SSS, preferences and trait attribution for their in
      group and the high status White out-group, but not the other low-status out
      group. With age White children generally demonstrated higher SSS for Black and
      Roma, preferred them more and attributed more positive traits. For low-status
      groups, an age effect was found only for Black children who preferred the Roma
      more with age and attributed more positive traits. Changes on preferences and
      trait attribution depending on age-group were mediated by SSS. It is concluded
      that minority group's SSS does not parallel the objective status hierarchy but,
      rather, is a dynamic reorganisation of group's relative positions serving
      strategies to cope with their minority condition. 

PMID- 24673335
TI  - In vivo antinociceptive and anti-inflammatory activities of umbelliferone
      isolated from Potentilla evestita.
AB  - This study was designed to evaluate the antinociceptive and anti-inflammatory
      activities of a compound, umbelliferone, isolated from the chloroform fraction of
      Potentilla evestita in animal models. When tested against acetic acid-induced
      noxious stimulus, it significantly prolonged pain threshold and provided 38.38%
      and 60.95% reduction in abdominal constriction at 5 and 10 mg/kg i.p.,
      respectively. Post-umbelliferone injection evoked significant dose-dependent
      reduction in noxious stimulation with 33.65% and 58.89% pain attenuation at 5 and
      10 mg/kg i.p., respectively, in the initial phase. In the late phase, it
      illustrated more dominant effect with 37.65% and 63.79% blockade of painful
      sensation. Similarly, it exhibited significant anti-inflammatory activity during
      various assessment times (1-5 h) with 46.28% and 66.13% amelioration after 4th of
      administration against induced oedema. In conclusion, umbelliferone possessed
      strong antinociceptive and anti-inflammatory activities by inhibiting both
      peripheral and centrally acting pain mediators.

PMID- 24673337
TI  - Chiral (LH)2L2Cu3 trinuclear paramagnetic nodes in octacyanidometalate-bridged
      helical chains.
AB  - Trinuclear chiral (LH)2L2Cu3 (LH = 1,3-diamino-2-propanol, bdapH) assemblies
      linked by octacyanidometalate(IV) form isostructural one-dimensional (1D) chains
      consisting of right- and left-handed helixes arranged in an alternate manner:
      [(bdapH)2(bdap)2Cu(II)3][M(IV)(CN)8].H2O (M = Mo 1, W 2). Each chain displays
      helicity with a long pitch around 17.2 A. The direction of the helix rotation is
      strictly connected with the conformation of the (LH)2L2Cu3 unit. Right-handed
      helixes are based on Delta-S,S-(LH)2L2Cu3, whereas left-handed ones contain
      Lambda-R,R-(LH)2L2Cu3 units. Magnetic studies reveal antiferromagnetic
      interactions through alkoxo-bridges inside trinuclear Cu(II) nodes leading to an
      ST = 1/2 ground state for both assemblies. 

PMID- 24673334
TI  - Simultaneous measurement of individual mitochondrial membrane potential and
      electrophoretic mobility by capillary electrophoresis.
AB  - Mitochondrial membrane potential varies, depending on energy demand, subcellular
      location, and morphology and is commonly used as an indicator of mitochondrial
      functional status. Electrophoretic mobility is a heterogeneous surface property
      reflective of mitochondrial surface composition and morphology, which could be
      used as a basis for separation of mitochondrial subpopulations. Since these
      properties are heterogeneous, methods for their characterization in individual
      mitochondria are needed to better design and understand electrophoretic
      separations of subpopulations of mitochondria. Here we report on the first method
      for simultaneous determination of individual mitochondrial membrane potential and
      electrophoretic mobility by capillary electrophoresis with laser-induced
      fluorescence detection (CE-LIF). Mitochondria were isolated from cultured cells,
      mouse muscle, or liver, and then polarized, labeled with JC-1 (a ratiometric
      fluorescent probe, which indicates changes in membrane potential), and separated
      with CE-LIF. Red/green fluorescence intensity ratios from individual mitochondria
      were used as an indicator of mitochondrial membrane potential. Reproducible
      distributions of individual mitochondrial membrane potential and electrophoretic
      mobility were observed. Analysis of polarized and depolarized regions of interest
      defined using red/green ratios and runs of depolarized controls allowed for the
      determination of membrane potential and comparison of electrophoretic mobility
      distributions in preparations containing depolarized mitochondria. Through
      comparison of these regions of interest, we observed dependence of
      electrophoretic mobility on membrane potential, with polarized regions of
      interest displaying decreased electrophoretic mobility. This method could be
      applied to investigate mitochondrial heterogeneity in aging or disease models
      where membrane potential is an important factor. 

PMID- 24673336
TI  - Use of sodium dodecyl sulfate pretreatment and 2-stage curing for improved
      quality of salted duck eggs.
AB  - The effects of use of sodium dodecyl sulfate (SDS) pretreatment and 2-stage
      curing on the microbial, physicochemical, and microstructural qualities of salted
      duck eggs were studied. After pretreatment in 0.5% (w/v) SDS solution at room
      conditions for 15 min, no discolorations were observed and no microorganisms were
      detected on the egg shells. In the 2-stage curing process, 25% (w/v) and 30%
      (w/v) saline solutions were evaluated in the 1st step (Stage I, approximately 18
      d), whereas 4% (w/v) saline solution was applied in the 2nd step (Stage II,
      approximately 15 d). Along with increased curing time, water content decreased
      and NaCl content increased in the egg yolks from approximately 0.40% to 0.86%,
      whereas the water content of egg albumen remained at approximately 85% during the
      2-stage curing. More importantly, the NaCl content of albumen maintained at
      approximately 4.0% at Stage II curing. Yolk index as a sign of maturity for
      salted duck eggs reached 1 at the end of Stage I (18 d) and retained the same
      value during Stage II curing regardless of the NaCl concentration in the Stage I
      saline solution. Oil exudation in egg yolks increased as the time of curing
      increased. As seen from scanning electron microscopy, oil was released from yolk
      granules. This study indicated that SDS pretreatment is effective to reduce
      microbial load on the shells of fresh duck eggs and the 2-stage curing can
      improve physicochemical qualities of the salted duck eggs and shortened curing
      time to about 7 to 17 d as compared to the traditional 1-step curing method.
      PRACTICAL APPLICATION: Spoiled saline solution and uneven distribution of salt
      are the 2 major problems in producing salted duck eggs. Sodium dodecyl sulfate
      (SDS) pretreatment and 2-stage curing process have shown effective to solve these
      problems, respectively. The SDS pretreatment was able to remove microorganisms
      and soil from the surface of fresh egg shells, thus preventing the spoilage of
      the saline solution. The 2-stage curing process successfully controlled the NaCl
      content of egg albumen and yolk in the final product, and shortened the curing
      time compared to the traditional 1-step curing method.

PMID- 24673338
TI  - Cloning and characterization of a novel beta-carotene hydroxylase gene from
      Lycium barbarum and its expression in Escherichia coli.
AB  - Lycium barbarum contains high levels of zeaxanthin, which is produced by the
      conversion of beta-carotene into zeaxanthin. beta-Carotene hydroxylase catalyzes
      this reaction. We cloned a cDNA (chyb) encoding beta-carotene hydroxylase (Chyb)
      from the L. barbarum leaf. A 939-bp full-length cDNA sequence was determined with
      3'-rapid amplification of cDNA end assay encoding a deduced Chyb protein (34.8
      kDa) with a theoretical isoelectric point of 8.36. A bioinformatics analysis
      showed that the L. barbarum Chyb was located in the chloroplast. Further, to
      investigate the catalytic activity of the L. barbarum Chyb, a complementation
      analysis was conducted in Escherichia coli. The results strongly demonstrated
      that Chyb can catalyze beta-carotene to produce zeaxanthin. Thus, this study
      suggests that L. barbarum beta-carotene hydroxylase could be a means of
      zeaxanthin production by genetic manipulation in E. coli. 

PMID- 24673339
TI  - Does body mass index influence the decline of glomerular filtration rate in
      diabetic type 2 patients with diabetic nephropathy in a developing country?
AB  - BACKGROUND: Diabetic nephropathy (DN) is associated with a high risk of
      progression to End Stage Renal Disease (ESRD). While obesity has been identified
      as a factor in the decline of the glomerular filtration rate (GFR) in chronic
      kidney disease, its role in the progression of DN remains controversial. The
      objective of this work is to determine GFR decline in relation to BMI in type 2
      diabetic (T2D) patients presenting a DN. METHODS: A prospective 5-year study
      conducted in the Eastern region of Morocco. Three BMI groups were distinguished:
      normal weight, overweight and obese and within each group progressors (eGFR > 5
      ml/min/1.73 m(2)/year) and non progressors (eGFR > 5 ml/min/1.73 m(2)/year).
      RESULTS: Data on 292 patients were compiled. The progressors represented 25.8%,
      23.1% and 32.3% of the normal weight, overweight and obese patient groups
      respectively (p = 0.29). ESRD was observed in 9.1%, 6.9% and 8.3% (p = 0.21) in
      normal weight, overweight and obese patients respectively. In multivariate
      analysis, low-baseline eGFR was identified as important predictor of progression
      of DN in each BMI group and in the entire cohort independently of BMI. Vascular
      co-morbidity events occurred in 9.1%, 16.9% and 19.8% (p = 0.04) in normal
      weight, overweight and obese patients respectively. CONCLUSION: Our results show
      that the decline of eGFR in the DN of T2D is not directly influenced by BMI and
      that the major risk factors contributing to this decline remain low-baseline eGFR
      and increased baseline albuminuria.

PMID- 24673340
TI  - Genomic analysis of Pseudomonas aeruginosa PA96, the host of carbapenem
      resistance plasmid pOZ176.
AB  - Pseudomonas aeruginosa PA96 is a clinical isolate from Guangzhou, China, that is
      multiresistant to antibiotics. We previously described the 500-kb IncP-2 plasmid,
      pOZ176 that encodes many resistance genes including the IMP-9 carbapenemase.
      Whole-genome sequencing of PA96 enabled characterization of its genomic islands,
      virulence factors, and chromosomal resistance genes. We filled gaps using PCR and
      used optical mapping to confirm the correct contig order. We automatically
      annotated the core genome and manually annotated the genomic islands. The genome
      is 6 444 091 bp and encodes 5853 ORFs. From the whole-genome sequence, we
      constructed a physical map and constructed a phylogenetic tree for comparison
      with sequenced P. aeruginosa strains. Analysis of known core genome virulence
      factors and resistance genes revealed few differences with other strains, but the
      major virulence island is closer to that of DK2 than to PA14. PA96 most closely
      resembles the environmental strain M18, and notably shares a common serotype,
      pyoverdin type, flagellar operon, type IV pilin, and several genomic islands with
      M18. 

PMID- 24673342
TI  - Choline-mediated modulation of hippocampal sharp wave-ripple complexes in vitro.
AB  - The cholinergic system is critically involved in the modulation of cognitive
      functions, including learning and memory. Acetylcholine acts through muscarinic
      (mAChRs) and nicotinic receptors (nAChRs), which are both abundantly expressed in
      the hippocampus. Previous evidence indicates that choline, the precursor and
      degradation product of Acetylcholine, can itself activate nAChRs and thereby
      affects intrinsic and synaptic neuronal functions. Here, we asked whether the
      cellular actions of choline directly affect hippocampal network activity. Using
      mouse hippocampal slices we found that choline efficiently suppresses
      spontaneously occurring sharp wave-ripple complexes (SPW-R) and can induce gamma
      oscillations. In addition, choline reduces synaptic transmission between
      hippocampal subfields CA3 and CA1. Surprisingly, these effects are mediated by
      activation of both mAChRs and alpha7-containing nAChRs. Most nicotinic effects
      became only apparent after local, fast application of choline, indicating rapid
      desensitization kinetics of nAChRs. Effects were still present following block of
      choline uptake and are, therefore, likely because of direct actions of choline at
      the respective receptors. Together, choline turns out to be a potent regulator of
      patterned network activity within the hippocampus. These actions may be of
      importance for understanding state transitions in normal and pathologically
      altered neuronal networks. In this study we asked whether choline, the precursor
      and degradation product of acetylcholine, directly affects hippocampal network
      activity. Using mouse hippocampal slices we found that choline efficiently
      suppresses spontaneously occurring sharp wave-ripple complexes (SPW-R). In
      addition, choline reduces synaptic transmission between hippocampal subfields.
      These effects are mediated by direct activation of muscarinic as well as
      nicotinic cholinergic pathways. Together, choline turns out to be a potent
      regulator of patterned activity within hippocampal networks. 

PMID- 24673343
TI  - Molecular cloning, expression and polymorphism of goose LRP8 gene.
AB  - 1. The low-density lipoprotein receptor-related protein 8 (LRP8), a member of the
      low-density lipoprotein receptor (LDLR) gene family, participates in the
      supplying of lipid during follicular development. The objective of the study was
      to identify and characterise the LRP8 gene in goose. 2. A 2867 bp fragment that
      covered the complete coding region (CDS) of goose (Anser cygnoides) LRP8 gene was
      cloned. It encoded a protein of 917 amino acid residues containing a 24-amino
      acid signal peptide and 5 functional domains. The goose LRP8 showed high nucleic
      acid and amino acid identities with those in other species. 3. Similarly to duck
      LRP8 gene, two splice variants of LRP8, LRP8-1 (containing 8 ligand-binding
      repeats) and LRP8-2 (containing 7 ligand-binding repeats), were identified in
      goose. 4. Semi-quantitative RT-PCR analysis indicates that the LRP8-1 transcript
      is expressed in heart, liver, spleen, lung, kidney, breast muscle, duodenum,
      hypothalamus, pituitary and ovary, negligible or absent in sebum and oviduct, and
      the LRP8-2 transcript is widely expressed in all examined tissues. 5. A total of
      7 SNPs were identified in the coding region of the goose LRP8 gene.

PMID- 24673345
TI  - An insight into nursing today.

PMID- 24673344
TI  - Transfusion-related acute lung injury and potential risk factors among the
      inpatient US elderly as recorded in Medicare claims data, during 2007 through
      2011.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is a serious
      complication leading to pulmonary edema and respiratory failure. This study's
      objective was to assess TRALI occurrence and potential risk factors among
      inpatient US elderly Medicare beneficiaries, ages 65 and older, during 2007
      through 2011. STUDY DESIGN AND METHODS: This retrospective claims-based study
      utilized large Medicare administrative databases. Transfusions were identified by
      recorded procedure and revenue center codes. TRALI was ascertained via ICD-9-CM
      diagnosis code. The study evaluated TRALI rates among the inpatient elderly
      overall and by calendar year, age, sex, race, blood components, and units
      transfused. Logistic regression analyses were used to assess potential risk
      factors. RESULTS: Of 11,378,264 inpatient transfusion stays for elderly Medicare
      beneficiaries, 2556 had a recorded TRALI diagnosis code, an overall rate of 22.46
      per 100,000 stays. TRALI rates were higher for platelet (PLT)- and plasma
      containing transfusions and increased by year and number of units transfused (p <
      0.0001). Significantly higher odds of TRALI were also found for persons ages 65
      to 79 years versus more than 79 years (OR, 1.19; 95% confidence interval CI, 1.09
      1.29), females versus males (OR, 1.26; 95% CI, 1.16-1.38), white versus nonwhite
      (OR, 1.43; 95% CI, 1.27-1.66), and with 6-month histories of postinflammatory
      pulmonary fibrosis (OR, 1.89; 95% CI, 1.52-2.20), tobacco use (OR, 1.16; 95% CI,
      1.00-1.26), and other diseases. CONCLUSION: Our study among the elderly suggests
      TRALI to be a severe event and identifies a substantially increased TRALI
      occurrence with greater number of units and with PLT- or plasma-containing
      transfusions. The study also suggests importance of underlying health conditions,
      prior recipient alloimmunization, and nonimmune mechanism in TRALI development
      among the elderly.

PMID- 24673346
TI  - When to use mixed methods.

PMID- 24673341
TI  - Diabetic retinopathy: loss of neuroretinal adaptation to the diabetic metabolic
      environment.
AB  - Diabetic retinopathy (DR) impairs vision of patients with type 1 and type 2
      diabetes, associated with vascular dysfunction and occlusion, retinal edema,
      hemorrhage, and inappropriate growth of new blood vessels. The recent success of
      biologic treatments targeting vascular endothelial growth factor (VEGF)
      demonstrates that treating the vascular aspects in the later stages of the
      disease can preserve vision in many patients. It would also be highly desirable
      to prevent the onset of the disease or arrest its progression at a stage
      preceding the appearance of overt microvascular pathologies. The progression of
      DR is not necessarily linear but may follow a series of steps that evolve over
      the course of multiple years. Abundant data suggest that diabetes affects the
      entire neurovascular unit of the retina, with an early loss of neurovascular
      coupling, gradual neurodegeneration, gliosis, and neuroinflammation occurring
      before observable vascular pathologies. In this article, we consider the
      pathology of DR from the point of view that diabetes causes measurable
      dysfunctions in the complex integral network of cell types that produce and
      maintain human vision. 

PMID- 24673347
TI  - Breaking from binaries - using a sequential mixed methods design.
AB  - AIM: To outline the traditional worldviews of healthcare research and discuss the
      benefits and challenges of using mixed methods approaches in contributing to the
      development of nursing and midwifery knowledge. BACKGROUND: There has been much
      debate about the contribution of mixed methods research to nursing and midwifery
      knowledge in recent years. DATA SOURCES: A sequential exploratory design is used
      as an exemplar of a mixed methods approach. The study discussed used a
      combination of focus-group interviews and a quantitative instrument to obtain a
      fuller understanding of women's experiences of childbirth. REVIEW METHODS: In the
      mixed methods study example, qualitative data were analysed using thematic
      analysis and quantitative data using regression analysis. DISCUSSION: Polarised
      debates about the veracity, philosophical integrity and motivation for conducting
      mixed methods research have largely abated. A mixed methods approach can
      contribute to a deeper, more contextual understanding of a variety of subjects
      and experiences; as a result, it furthers knowledge that can be used in clinical
      practice. CONCLUSION: The purpose of the research study should be the main
      instigator when choosing from an array of mixed methods research designs. Mixed
      methods research offers a variety of models that can augment investigative
      capabilities and provide richer data than can a discrete method alone.
      IMPLICATIONS FOR PRACTICE/RESEARCH: This paper offers an example of an
      exploratory, sequential approach to investigating women's childbirth experiences.
      A clear framework for the conduct and integration of the different phases of the
      mixed methods research process is provided. This approach can be used by
      practitioners and policy makers to improve practice.

PMID- 24673348
TI  - Reflections on the added value of using mixed methods in the SCAPE study.
AB  - AIM: To reflect on the added value that a mixed method design gave in a large
      national evaluation study of specialist and advanced practice (SCAPE), and to
      propose a reporting guide that could help make explicit the added value of mixed
      methods in other studies. BACKGROUND: Recently, researchers have focused on how
      to carry out mixed methods research (MMR) rigorously. The value-added claims for
      MMR include the capacity to exploit the strengths and compensate for weakness
      inherent in single designs, generate comprehensive description of phenomena,
      produce more convincing results for funders or policy-makers and build
      methodological expertise. DATA SOURCES: Data illustrating value added claims were
      drawn from the SCAPE study. REVIEW METHODS: Studies about the purpose of mixed
      methods were identified from a search of literature. DISCUSSION: The authors
      explain why and how they undertook components of the study, and propose a
      guideline to facilitate such studies. CONCLUSION: If MMR is to become the third
      methodological paradigm, then articulation of what extra benefit MMR adds to a
      study is essential. The authors conclude that MMR has added value and found the
      guideline useful as a way of making value claims explicit. IMPLICATIONS FOR
      PRACTICE/RESEARCH: The clear articulation of the procedural aspects of mixed
      methods research, and identification of a guideline to facilitate such research,
      will enable researchers to learn more effectively from each other.

PMID- 24673349
TI  - Challenges and solutions during analysis in a longitudinal narrative case study.
AB  - AIM: To describe the challenges faced by those performing complex qualitative
      analysis during a narrative study and to offer solutions. BACKGROUND: Qualitative
      research requires rigorous analysis. However, novice researchers often struggle
      to identify appropriately robust analytical procedures that will move them from
      their transcripts to their final findings. The lack of clear and detailed
      accounts in the literature that consider narrative analysis and how to address
      some of the common challenges researchers face add to this problem. DATA SOURCES:
      A longitudinal narrative case study exploring the personal and familial changes
      reported by uninjured family members during the first year of another family
      member's traumatic brain injury. Review methods This is a methodological paper.
      DISCUSSION: The challenges of analysis included: conceptualising analysis;
      demonstrating the relationship between the different analytical layers and the
      final research findings; interpreting the data in a way that reflected the
      priorities of a narrative approach; and managing large quantities of data. The
      solutions explored were: the mapping of analytic intentions; aligning analysis
      and interpretation with the conceptual framework; and the use of matrices to
      store and manage quotes, codes and reflections. CONCLUSION: Working with
      qualitative data can be daunting for novice researchers. Ensuring rigorous,
      transparent, and auditable data analysis procedures can further constrain the
      interpretive aspect of analysis. Implications for research/practice The solutions
      offered in this paper should help novice researchers to manage and work with
      their data, assisting them to develop the confidence to be more intuitive and
      creative in their research.

PMID- 24673350
TI  - Study of irritable bowel syndrome and co-existing psychological illness.
AB  - AIM: To assess the feasibility of using qualitative methods to explore
      psychological comorbidities associated with irritable bowel syndrome (IBS).
      BACKGROUND: IBS is a condition that often has a significant effect on quality of
      life. It has a high prevalence of co-existing psychological illness, which has
      been associated with more severe and persistent symptoms and an increased need
      for specialist referral. Only a small number of research studies have explored
      patients' perceptions and experiences of IBS, particularly when they are
      compounded by the presence of psychological comorbidity. DATA SOURCES: Semi
      structured interview methods were used to explore the patients' experiences and
      perceptions of IBS and co-existing psychological illness. REVIEW METHODS: All
      interview data were transcribed before conducting a thematic analysis.
      DISCUSSION: The paper reports the methods used to conduct a small feasibility
      study and discusses and justifies these methods. Methodological issues and the
      implications these may have on the conduct of the study are presented and
      critically discussed. CONCLUSION: Important issues were identified during the
      design and conduct of the feasibility study relating to the quality of
      participant information, participant recruitment and the suitability of the
      proposed methods. IMPLICATIONS FOR RESEARCH/PRACTICE: Semi-structured interviews
      are suitable methods for exploring complex issues such as the psychological
      comorbidities associated with IBS. Further research should explore the patient
      perception and experience of concomitant psychological illness, which would help
      researchers develop effective interventions for patients with IBS.

PMID- 24673351
TI  - Methodological and ethical issues related to qualitative telephone interviews on
      sensitive topics.
AB  - AIM: To explore the methodological and ethical issues of conducting qualitative
      telephone interviews about personal or professional trauma with critical care
      nurses. BACKGROUND: The most common method for conducting interviews is face-to
      face. However, there is evidence to support telephone interviewing on a variety
      of sensitive topics including post-traumatic stress disorder (PTSD). Qualitative
      telephone interviews can limit emotional distress because of the comfort
      experienced through virtual communication. Critical care nurses are at increased
      risk of developing PTSD due to the cumulative exposure to work-related stress in
      the intensive care unit. We explored the methodological and ethical issues of
      conducting qualitative telephone interviews, drawing on our experiences
      communicating with a group of critical care nurses. DATA SOURCES: Qualitative
      research interviews with 27 critical care nurses. Fourteen of the nurses met the
      diagnostic criteria for PTSD; 13 did not and had scores consistent with high
      levels of resilience. REVIEW METHODS: This is a methodology paper on the authors'
      experiences of interviewing critical care nurses on sensitive topics via the
      telephone. DISCUSSION: The authors found that establishing rapport and
      connections with the participants and the therapeutic use of non-verbal
      communication were essential, and fostered trust and compassion. The ethical
      issues of this mode of communication include protecting the privacy and
      confidentiality associated with the disclosure of sensitive information, and
      minimising the risk of psychological harm to the researcher and participants.
      CONCLUSION: Qualitative telephone interviews are a valuable method of collecting
      information on sensitive topics. IMPLICATIONS FOR RESEARCH/PRACTICE: This paper
      explores a method of interviewing in the workplace. It will help inform
      interventions to promote healthy adaptation following trauma exposure in the
      intensive care unit.

PMID- 24673352
TI  - Fact or fiction: exploring the use of real stories in place of vignettes in
      interviews with informal carers.
AB  - AIM: To consider the development and use of real stories rather than vignettes in
      interviews. BACKGROUND: Effective interprofessional working critically informed
      by the perspectives of informal carers was considered by the research team to be
      under-researched. It was proposed initially to use fictional vignettes as
      triggers in interviews with informal carers. It could be argued that the vignette
      does not represent the voice of the individual or may only represent a particular
      experience. Stories acknowledge a person's expertise in his or her experiences. A
      decision was made early in the design process to use real stories instead of
      vignettes. DATA SOURCES: A descriptive naturalistic design using a participatory
      approach. Two stories were developed by the researcher and two informal carers,
      and then used in interviews with other carers to explore their experiences and
      perceptions of interprofessional working. REVIEW METHODS: The paper provides a
      discussion of an alternative approach to data collection. DISCUSSION: The stories
      promoted a sense of support for the participants, which they gained from
      listening to and sharing stories of caring. This approach offered a different
      experience for the carers from the standard interview format. CONCLUSION: The
      paper describes the use of real stories in interviews, which is not a commonly
      reported method. Carers were involved in both the development and the use of the
      stories in the interviews. Those interviewed valued the credibility gained by
      using these real stories, as opposed to constructed vignettes. IMPLICATIONS FOR
      RESEARCH/PRACTICE: Using stories in this way contributes to methodological
      development, which allows perceptions and experiences to be captured.

PMID- 24673353
TI  - How to be a pioneer in your chosen field.

PMID- 24673356
TI  - Effect of sustained use of platelet aggregation inhibitors on post-endoscopic
      sphincterotomy bleeding.
AB  - BACKGROUND AND AIM: The effect of platelet aggregation inhibitors (PAI) on post
      endoscopic sphincterotomy (ES) bleeding in patients who cannot discontinue PAI
      for sufficient time in urgent conditions has not been identified. The present
      study analyzed the effect of sustained use of PAI on post-procedural bleeding in
      patients undergoing ES. METHODS: A total of 762 patients were grouped into one of
      the following groups: no-PAI group (n = 601), continuation group (n = 132), and
      withdrawal group (n = 29). The continuation group included sustained PAI therapy
      (sustained user, n = 49) or those in whom therapy was interrupted <7 days prior
      to ES (non-sustained user, n = 83). The primary outcome was defined as the
      incidence, type, and severity of post-ES bleeding among groups. RESULTS: There
      were no significant differences between incidence, type, or severity of post-ES
      bleeding in the three groups. Among 132 patients with continued use of PAI, there
      was no significant difference regarding incidence and severity of bleeding
      according to sustained or non-sustained use (P = 0.071 and P = 0.086,
      respectively). However, post-ES delayed bleeding was more frequent in sustained
      PAI users than in non-sustained users (7/49, 14.3% vs 2/83, 2.4%) and was
      significantly associated with sustained PAI therapy in the continuation group (P
      = 0.013). CONCLUSION: Sustained use of PAI without interruption until ES might
      increase the risk of delayed bleeding.

PMID- 24673357
TI  - Long-term efficacy and safety of infliximab maintenance therapy in patients with
      plaque-type psoriasis in real-world practice.
AB  - BACKGROUND: Tumour necrosis factor-alpha inhibitors, including infliximab (IFX),
      can improve disease control of plaque-type psoriasis. OBJECTIVES: The Real-World
      Assessment of Long-Term Infliximab Therapy for Psoriasis (REALITY) study
      evaluated the efficacy and safety of maintenance IFX therapy in typical clinical
      settings. METHODS: In this prospective, observational, open-label, multicentre
      study in patients with plaque-type psoriasis, IFX 5 mg kg was infused at weeks 0,
      2 and 6, and every 8 weeks thereafter during a 50-week treatment phase. The
      primary outcome was >= 75% Psoriasis Area and Severity Index (PASI) improvement
      from baseline to week 50. Patients with >= 25% PASI improvement from baseline to
      the end of the treatment phase were potentially eligible to enter a 48-week
      extended treatment phase. Response maintenance and other efficacy measures were
      evaluated. Adverse events (AEs) were collected. RESULTS: In total 660 patients
      enrolled. Of 521 efficacy-evaluable treatment phase patients (66% male, mean age
      46.5 years, mean PASI 18.1), 56.8% achieved PASI 75 at the end of the treatment
      phase. Response was maintained at week 50 by 64.7% (205/317) of patients who
      achieved PASI 75 at week 14. During extended treatment, 66.3% (112/169) of
      patients attained PASI 75 at week 98; response was maintained at week 98 by 71.6%
      (101/141) of those who achieved PASI 75 at week 50. IFX was generally well
      tolerated. During treatment, 7.6% (50/659) of patients had serious AEs. During
      extended treatment, 4.1% (eight of 193) of patients had serious AEs. CONCLUSIONS:
      PASI 75 response was achieved by 56.8% and 66.3% of patients at weeks 50 and 98,
      respectively. The AE pattern was consistent with previous reports.

PMID- 24673358
TI  - Type III or allosteric kinase inhibitors for the treatment of non-small cell lung
      cancer.
AB  - INTRODUCTION: In recent times, there has been much interest in the development of
      pharmacological kinase inhibitors that treat NSCLC. Furthermore, treatment
      options have been guided by the development of a wide panel of synthetic small
      molecule kinase inhibitors. Most of the molecules developed belong to the type I
      class of inhibitors that target the ATP-binding site in its active conformation.
      The high sequence similarity in the ATP-binding site among members of the kinase
      families often results in low selectivity and additional toxicities. Also, second
      mutations in the ATP-binding site, such as threonine to methionine at position
      790, have been described as a mechanism of resistance to ATP-competitive kinase
      inhibitors. For these reasons, alternative drug development approaches targeting
      sites other than the ATP cleft are being pursued. The class III or allosteric
      inhibitors, which bind outside the ATP-binding site, have been shown to
      negatively modulate kinase activity. AREAS COVERED: In this review, the authors
      discuss the most well-characterised allosteric inhibitors that have reached
      clinical development in NSCLC. EXPERT OPINION: Great progress has made in
      developing inhibitors with entirely new modes of action. That being said, it is
      important to highlight that despite their apparent simplicity, biochemical assays
      will remain at the core of drug discovery activities to better explore these new
      opportunities.

PMID- 24673359
TI  - Nevus anelasticus: how should such lesions be classified?
AB  - Nevus anelasticus represents a rare entity that is most commonly classified as a
      connective tissue nevus. It typically presents before 20 years of age with
      asymmetrically distributed white-to-skin-toned or pink-to-red papules or plaques
      on the trunk and upper extremities. The lesion is defined histopathologically by
      the absence or degeneration of elastic fibers in the dermis. We report the case
      of a healthy 17-year-old female who presented with an asymptomatic slowly
      progressive plaque on the right inferior areola. Histopathologic examination
      showed the absence of elastic fibers in the papillary and upper reticular dermis
      and fragmented elastic tissue fibers in the deep reticular dermis. Although there
      is ongoing controversy regarding the nosology of this uncommon disorder, we
      propose that it is a distinct entity based on its histopathologic and clinical
      features. 

PMID- 24673360
TI  - Evaluation of serum sCD40L and homocysteine levels with subclinical
      atherosclerosis indicators in patients with psoriasis: a pilot study.
AB  - Psoriasis is a chronic inflammatory process associated with an increased risk of
      cardiovascular risk factors. sCD40L has been suggested to have a possible role in
      the pathogenesis, of psoriasis and is known to be associated with inflammation,
      atherogenesis and cardiovascular events. This study investigated cardiovascular
      risk factors (sCD40L and homocysteine) as well as subclinical atherosclerosis
      indicators in psoriatic patients and control subjects. The study included 56
      consecutive patients with chronic plaque-type psoriasis and 53 age and gender
      matched healthy controls admitted to a university hospital. Serum sCD40L and
      homocysteine levels were measured by ELISA. Carotid artery intima-media thickness
      and brachial artery flow mediated dilatation (FMD) measurements were determined
      ultrasonographically. Subjects who had a history of cardiovascular diseases and
      cardiovascular risk factors and receiving any systemic treatment were excluded
      from the study. Plasma sCD40L levels were significantly higher in psoriasis
      patients compared with healthy controls (1.33+/-0.72 vs. 0.98+/-0.70 ng/ml
      P=0.012), whereas plasma homocysteine levels did not differ significantly between
      the two groups. FMD was significantly reduced in the psoriasis group compared to
      the controls (3.83+/-5.03 vs. 8.45+/-7.27% P=0.0001). Multiple linear regression
      analyses indicated a significant association between psoriasis, sCD40L, and FMD.
      Psoriatic patients had higher sCD40L levels than healthy controls, which may lead
      to an increase in cardiovascular diseases. sCD40L may be a more reliable and
      early predictive marker of cardiovascular events in psoriatic patients. New
      treatmentoptions that will be developed over sCD40L will benefit in prevention of
      psoriasis and its cardiovascular comorbidities.

PMID- 24673361
TI  - Generating and stabilizing Co(I) in a nanocage environment.
AB  - A discrete nanocage of core-shell design, in which carboxylic acid groups were
      tethered to the core and silanol to the shell interior, was found to react with
      Co2(CO)8 to form and stabilize a Co(I)-CO species. The singular CO stretching
      band of this new Co species at 1958 cm(-1) and its magnetic susceptibility were
      consistent with Co(I) compounds. When exposed to O2, it transformed from an EPR
      inactive to an EPR active species indicative of oxidation of Co(I) to Co(II) with
      the formation of H2O2. It could be oxidized also by organoazide or water. Its
      residence in the nanocage interior was confirmed by size selectivity in the
      oxidation process and the fact that the entrapped Co species could not be
      accessed by an electrode. 

PMID- 24673363
TI  - Lipid-lipid interactions in aminated reduced graphene oxide interface for
      biosensing application.
AB  - A label-free biosensor based on antiapolipoprotein B 100 functionalized-aminated
      reduced graphene oxide interface has been fabricated for detection of low density
      lipoprotein (LDL or lipid) cholesterol. The aminated reduced graphene oxide (NH2
      rGO) based electrode surface is covalently functionalized with antiapolipoprotein
      B 100 (AAB or lipid) using EDC/NHS coupling chemistry. The lipid-lipid
      interactions at the NH2-rGO electrode surface have been investigated using
      electrochemical impedance spectroscopic technique. The structural and
      morphological investigations of NH2-rGO based immunosensor have been accomplished
      via transmission electron microscopy, X-ray diffraction, Fourier transform
      infrared spectroscopy, UV-visible, and electrochemical techniques. The
      impedimetric response of the proposed immunosensor shows excellent sensitivity
      (612 Omega mg(-1) dL cm(-2)), a response time of 250 s, and a low detection limit
      of 5 mg/dL of LDL molecules. The association, dissociation, and equilibrium rate
      constants for this immunoelectrode are found to be 1.66 M(-1) s(-1), 0.6 s(-1),
      and 2.77 M(-1), respectively. The long-term stability and excellent
      reproducibility of the proposed immunosensor indicates a suitable platform for
      detection of LDL or lipid molecules. This immunosensor provides an efficient
      platform for analysis of the antigen-antibody interactions of lipid molecules. 

PMID- 24673362
TI  - Patterns of Adherence to Oral Hypoglycemic Agents and Glucose Control among
      Primary Care Patients with Type 2 Diabetes.
AB  - Researchers sought to examine whether there are patterns of oral hypoglycemic
      agent adherence among primary-care patients with type 2 diabetes that are related
      to patient characteristics and clinical outcomes. Longitudinal analysis via
      growth curve mixture modeling was carried out to classify 180 patients who
      participated in an adherence intervention according to patterns of adherence to
      oral hypoglycemic agents across 12 weeks. Three patterns of change in adherence
      were identified: adherent, increasing adherence, and nonadherent. Global
      cognition and intervention condition were associated with pattern of change in
      adherence (p < .05). Patients with an increasing adherence pattern were more
      likely to have an Hemoglobin A1c (HbA1c) < 7%; adjusted odds ratio = 14.52, 95%
      CI (2.54, 82.99) at 12 weeks, in comparison with patients with the nonadherent
      pattern. Identification of patients with type 2 diabetes at risk of nonadherence
      is important for clinical prognosis and the development and delivery of
      interventions. 

PMID- 24673364
TI  - Health status, function, productivity, and costs among individuals with
      idiopathic painful peripheral neuropathy with small fiber involvement in the
      United States: results from a retrospective chart review and cross-sectional
      survey.
AB  - OBJECTIVE: To characterize the burden of idiopathic painful peripheral neuropathy
      with small fiber involvement (idiopathic SFN) by pain severity in the US.
      METHODS: One hundred previously diagnosed idiopathic SFN subjects were enrolled
      during routine office visits. Subjects completed a one-time questionnaire, and
      investigators reported clinical characteristics and healthcare resource use,
      based on 6 month retrospective chart review. Annualized direct and indirect costs
      were estimated. Results were stratified across pain severity groups. RESULTS:
      Mean age was 63.5 years; 53.0% were female; 76.0% had moderate or severe pain.
      Most common comorbidities were sleep disturbance/insomnia (37.0%), anxiety
      (34.0%), and depressive symptoms (33.0%). Overall mean health status (0.59; -0.11
      1.00 scale), physical and mental health (31.7 and 45.6, respectively, 0-100
      scale), sleep index (45.1; 0-100 scale), and pain interference with function
      (5.0; 0-10 scale) differed by pain severity, with worse outcomes among those with
      greater pain (all p < 0.002). 84.0% were prescribed >=1 SFN medication. 16.0%
      were employed; mean overall work impairment was 36.9%. Annualized average
      adjusted direct and indirect costs per subject ($8055 and $13,733, respectively)
      differed by pain severity. CONCLUSIONS: Idiopathic SFN subjects with pain
      experience moderate or severe pain, which negatively impacts health status,
      function, and productivity, and leads to substantial direct and indirect costs.

PMID- 24673365
TI  - Corncob hydrolysate, an efficient substrate for Monascus pigment production
      through submerged fermentation.
AB  - Monascus pigment has traditionally been produced by the fermentation of Monascus
      using rice powder or glucose as a culture substrate. Submerged fermentation can
      produce stable Monascus pigment yield and control the accumulation of the by
      product, citrinin, which can then be more easily removed. To reduce the cost of
      Monascus submerged fermentation, the feasibility of corncob hydrolysate as an
      alternative substrate was investigated. Results showed that, when compared with a
      conventional glucose medium, the corncob hydrolysate medium produced an
      equivalent pigment yield without stimulating citrinin accumulation. Furthermore,
      the corncob hydrolysate medium and cultivation conditions were optimized to
      enhance pigment production and decrease citrinin synthesis. When Monascus sp. was
      cultured under dark conditions in the presence of caprylic acid, pigment
      production was increased to 25.8 +/- 0.8 UA500 /mL, which was higher than that
      achieved in a glucose medium (24.0 +/- 0.9 UA500 /mL), and those obtained in
      previously reported Monascus submerged fermentations using the same yield unit;
      on the other hand, citrinin accumulation was decreased to 26.2 +/- 1.9 ug/L,
      which was significantly lower than that generated in the glucose control (44.3 +/
      2.2 ug/L) and in those previously reported fermentations. Thus, corncob
      hydrolysate was proved to be an efficient alternative substrate for Monascus
      pigment production through submerged fermentation, which showed significant
      advantages over a conventional glucose substrate. 

PMID- 24673366
TI  - Tryptic digestion coupled with ambient desorption electrospray ionization and
      liquid extraction surface analysis mass spectrometry enabling identification of
      skeletal muscle proteins in mixtures and distinguishing between beef, pork,
      horse, chicken, and turkey meat.
AB  - The use of ambient desorption electrospray ionization mass spectrometry (DESI-MS)
      and liquid extraction surface analysis mass spectrometry (LESA-MS) is explored
      for the first time to analyze skeletal muscle proteins obtained from a mixture of
      standard proteins and raw meat. Single proteins and mixtures of up to five
      proteins (myoglobin, troponin C, actin, bovine serum albumin (BSA), tropomyosin)
      were deposited onto a polymer surface, followed by in situ tryptic digestion and
      comparative analysis using DESI-MS and LESA-MS using tandem electrospray MS.
      Peptide peaks specific to individual proteins were readily distinguishable with
      good signal-to-noise ratio in the five-component mixture. LESA-MS gave a more
      stable analysis and greater sensitivity compared with DESI-MS. Meat tryptic
      digests were subjected to peptidomics analysis by DESI-MS and LESA-MS. Bovine,
      horse, pig, chicken, and turkey muscle digests were clearly discriminated using
      multivariate data analysis (MVA) of the peptidomic data sets. The most abundant
      skeletal muscle proteins were identified and correctly classified according to
      the species following MS/MS analysis. The study shows, for the first time, that
      ambient ionization techniques such as DESI-MS and LESA-MS have great potential
      for species-specific analysis and differentiation of skeletal muscle proteins by
      direct surface desorption. 

PMID- 24673367
TI  - A new antioxidant stilbene and other constituents from the stem bark of Morus
      nigra L.
AB  - A new stilbene, 2',3,4',5,5'-pentahydroxy-cis-stilbene (1), along with 13 known
      compounds, resveratrol (2), oxyresveratrol (3), norartocarpetin (4), kuwanon C
      (5), morusin (6), cudraflavone A (7), kuwanon G (8), albafurane C (9),
      mulberrofuran G (10), 3-O-acetyl-alpha-amyrin (11), 3-O-acetyl-beta-amyrin (12)
      ursolic acid-3-O-acetate (13) and uvaol (14), were isolated from the barks of
      Morus nigra. Compounds 2, 8, 10, 12 and 14 are reported for the first time from
      this plant. The isolated compounds were elucidated by means of 1D and 2D NMR, UV,
      IR and MS, as well as by comparison with the literature data. The isolated
      compounds and the different extracts were evaluated for their potential
      antioxidant activity using 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic
      acid)(+) radical-scavenging capacity assay and compared with ascorbic acid. The
      new stilbene (1) exhibited remarkable antioxidant capacity with IC50 of 4.69 MUM.

PMID- 24673368
TI  - Impaired health-related quality of life in acute myeloid leukemia survivors: a
      single-center study.
AB  - OBJECTIVES: The purpose of this study was to assess the impact of acute myeloid
      leukemia (AML) and its treatment on health-related quality of life (HRQOL) by
      comparing the HRQOL of AML survivors with the HRQOL in the general population.
      METHODS: Two HRQOL questionnaires (EQ-5D and QLQ-C30) were sent to patients
      diagnosed with AML between 1999 and 2011 at a single academic hospital and still
      alive in 2012. HRQOL in AML survivors was compared with general population
      reference values. Multivariate analysis was used to identify factors associated
      with HRQOL in AML survivors. RESULTS: Questionnaires were returned by 92 of the
      103 patients (89%). AML survivors reported significantly worse functioning, more
      fatigue, pain, dyspnea, appetite loss, and financial difficulties and lower EQ
      VAS scores than the general population (P < 0.05). Impaired HRQOL in AML
      survivors was mainly found in survivors without a paid job. Other factors
      associated with a poor HRQOL were allogeneic hematopoietic stem cell
      transplantation and the absence of social support. CONCLUSION: This single-center
      study showed that the HRQOL in AML survivors is worse than the HRQOL in the
      general population. HRQOL in these patients can be improved by adequately
      treating and preventing fatigue, pain, dyspnea, and appetite loss.

PMID- 24673369
TI  - Asymptomatic elevation of creatine kinase in patients with hyponatremia.
AB  - Elevated creatine kinase (hyper-CKemia) has been observed in small number of
      patients with hyponatremia. This study evaluated the features and outcomes of
      patients admitted with hyponatremia complicated by hyper-CKemia. Patients
      admitted with hyponatremia and concurrently found to have elevated creatine
      kinase (CK) of above 375 IU/L (male) or 225 IU/L (female), over a 5-year period
      were retrospectively reviewed. Those with myocardial injury (elevated CK-MB
      isoenzyme [CK-MB/CK percentage of >2.5%] or Troponin T [>0.02 MUg/L]), traumatic
      or ischemic muscle damage, primary myopathic disorder, seizures prior to CK
      measurement or those taking medications which can cause myopathy, were excluded.
      Thirty-two patients with hyponatremia and hyper-CKemia were identified. All
      patients had no muscular symptoms or weakness. The commonest cause of
      hyponatremia in this cohort was related to diuretics (50%). The mean sodium level
      on presentation was 116.0 +/- 6.9 mmol/L and the median peak CK was 895.5
      (interquartile range: 610.8-1691.8) IU/L. Six (18%) patients developed acute
      kidney injury (AKI). The length of hospital admission of the entire cohort was
      8.0 +/- 5.8 days. Patients with hyper-CKemia in the setting of diuretic
      associated hyponatremia were older and had longer hospital length of stay
      compared with primary-polydipsia-associated. Asymptomatic hyper-CKemia is an
      uncommon association with hyponatremia of various etiologies. Hyponatremia
      associated hyper-CKemia can be complicated by AKI.

PMID- 24673370
TI  - Energy upconversion in lanthanide-doped core/porous-shell nanoparticles.
AB  - Here, we report upconversion nanoparticles with a core/porous-shell structure in
      which bulk emission and nanoemission are simultaneously observed. The activated
      porous shell can efficiently tune the bulk emission but has negligible influence
      on the nanoemission. 

PMID- 24673371
TI  - Potential application of algicidal bacteria for improved lipid recovery with
      specific algae.
AB  - The utility of specific strains of natural algicidal bacteria isolated from
      shallow wetland sediments was evaluated against several strains of algae with
      potential immediate or future commercial value. Two strains of bacteria,
      Pseudomonas pseudoalcaligenes AD6 and Aeromonas hydrophila AD9, were identified
      and demonstrated to have algicidal activity against the microalgae Neochloris
      oleoabundans and Dunaliella tertiolecta. These bacteria were further evaluated
      for the potential to improve lipid extraction using a mild solvent extraction
      approach. Aeromonas hydrophila AD9 showed a nearly 12-fold increase in lipid
      extraction with D. tertiolecta, while both bacteria showed a sixfold improvement
      in lipid extraction with N. oleoabundans. 

PMID- 24673372
TI  - Economic analysis of opportunities to accelerate Alzheimer's disease research and
      development.
AB  - The development of disease-modifying treatments for Alzheimer's disease (AD)
      faces a number of barriers. Among these are the lack of surrogate biomarkers, the
      exceptional size and duration of clinical trials, difficulties in identifying
      appropriate populations for clinical trials, and the limitations of monotherapies
      in addressing such a complex multifactorial disease. This study sets out to first
      estimate the consequent impact on the expected cost of developing disease
      modifying treatments for AD and then to estimate the potential benefits of
      bringing together industry, academic, and government stakeholders to co-invest
      in, for example, developing better biomarkers and cognitive assessment tools,
      building out advanced registries and clinical trial-readiness cohorts, and
      establishing clinical trial platforms to investigate combinations of candidate
      drugs and biomarkers from the portfolios of multiple companies. Estimates based
      on interviews with experts on AD research and development suggest that the cost
      of one new drug is now $5.7 billion (95% confidence interval (CI) $3.7-9.5
      billion) and could be reduced to $2.0 billion (95% CI $1.5-2.9 billion). The
      associated acceleration in the arrival of disease-modifying treatments could
      reduce the number of case years of dementia by 7.0 million (95% CI 4.4-9.4
      million) in the United States from 2025 through 2040. 

PMID- 24673374
TI  - Modeling with the logistic regression of the growth/no growth interface of
      Saccharomyces cerevisiae in relation to 2 antimicrobial terpenes (citral and
      linalool), pH, and a(w).
AB  - The antimicrobial effects of 2 terpenes (citral and linalool) on a Saccharomyces
      cerevisiae strain isolated from spoiled soft drink have been evaluated, alone or
      in combination, in relation to pH and aw using in vitro assays. The obtained data
      were fitted with the logit model to find the growth/no growth boundary regions of
      the 2 terpenes, focusing the attention on the type of interaction exerted by
      citral and linalool. In particular, the results showed an increase of citral
      antimicrobial effect in growth media characterized by low aw value, as well as a
      higher linalool antimicrobial effect in media at low pH. Moreover, the
      interactive effects of the 2 terpenes were exploited. The results obtained with
      the model were validated in an independent experiment. The knowledge of the
      interactions of essential oil molecules with enhanced antimicrobial activity, in
      relation to some of the most important chemicophysical variables, can have
      important industrial applications, since these substances are able to assure the
      desired antimicrobial effect without negatively modifying the product flavor
      profile. PRACTICAL APPLICATION: The effects of the main chemicophysical
      parameters (such as aw and pH) on the antimicrobial activity of bioactive
      terpenes are necessary for the definition of an industrially applicable
      preservation strategy based on the use of essential oils as natural
      antimicrobials aimed to prolong shelf life of food products.

PMID- 24673375
TI  - Analysis of structural rearrangements of poly(lactic acid) in the presence of
      water.
AB  - The effects of hydration on two types of structural rearrangements, physical
      aging and crystallization, of poly(lactic acid) (PLA) have been characterized.
      Although the water absorbed is extremely small, on the order of 0.5% by weight,
      we found a significant increase in both the magnitude and kinetics of enthalpic
      relaxation near the glass transition temperature (Tg). The kinetics of aging is
      at least 2 times the speed as compared to dry samples. In addition, we also found
      that the crystallization kinetics can be increased significantly when PLA is
      hydrated. The initial rate of crystallization at 80  degrees C is extremely fast
      at 7 J/g/min for the hydrated state as compared to 2 J/g/min under dry
      conditions. However, the ultimate degree of crystallinity achieved is not
      different for the two types of samples. Both of these structural rearrangements
      in the hydrated state can be explained by an increase in segmental mobility. The
      fact that water has such a strong effect on PLA structure is attributed to the
      strong intermolecular interactions present and their changes in the hydrated
      state. Spectroscopic features associated with bound water or free water were
      found for PLA with different hydration levels. The increase in the segmental
      mobility was directly correlated to the presence of free liquid water disrupting
      the intermolecular interactions in PLA. 

PMID- 24673373
TI  - Cancer cell membrane-coated nanoparticles for anticancer vaccination and drug
      delivery.
AB  - Cell-derived nanoparticles have been garnering increased attention due to their
      ability to mimic many of the natural properties displayed by their source cells.
      This top-down engineering approach can be applied toward the development of novel
      therapeutic strategies owing to the unique interactions enabled through the
      retention of complex antigenic information. Herein, we report on the biological
      functionalization of polymeric nanoparticles with a layer of membrane coating
      derived from cancer cells. The resulting core-shell nanostructures, which carry
      the full array of cancer cell membrane antigens, offer a robust platform with
      applicability toward multiple modes of anticancer therapy. We demonstrate that by
      coupling the particles with an immunological adjuvant, the resulting formulation
      can be used to promote a tumor-specific immune response for use in vaccine
      applications. Moreover, we show that by taking advantage of the inherent
      homotypic binding phenomenon frequently observed among tumor cells the membrane
      functionalization allows for a unique cancer targeting strategy that can be
      utilized for drug delivery applications. 

PMID- 24673377
TI  - Elevating the quality of disability and rehabilitation research: mandatory use of
      the reporting guidelines.

PMID- 24673376
TI  - Comparison of peptide-major histocompatibility complex tetramers and dextramers
      for the identification of antigen-specific T cells.
AB  - Fluorochrome-conjugated peptide-major histocompatibility complex (pMHC) multimers
      are widely used for flow cytometric visualization of antigen-specific T cells.
      The most common multimers, streptavidin-biotin-based 'tetramers', can be
      manufactured readily in the laboratory. Unfortunately, there are large
      differences between the threshold of T cell receptor (TCR) affinity required to
      capture pMHC tetramers from solution and that which is required for T cell
      activation. This disparity means that tetramers sometimes fail to stain antigen
      specific T cells within a sample, an issue that is particularly problematic when
      staining tumour-specific, autoimmune or MHC class II-restricted T cells, which
      often display TCRs of low affinity for pMHC. Here, we compared optimized staining
      with tetramers and dextramers (dextran-based multimers), with the latter carrying
      greater numbers of both pMHC and fluorochrome per molecule. Most notably, we find
      that: (i) dextramers stain more brightly than tetramers; (ii) dextramers
      outperform tetramers when TCR-pMHC affinity is low; (iii) dextramers outperform
      tetramers with pMHC class II reagents where there is an absence of co-receptor
      stabilization; and (iv) dextramer sensitivity is enhanced further by specific
      protein kinase inhibition. Dextramers are compatible with current state-of-the
      art flow cytometry platforms and will probably find particular utility in the
      fields of autoimmunity and cancer immunology. 

PMID- 24673378
TI  - Guanosine protects C6 astroglial cells against azide-induced oxidative damage: a
      putative role of heme oxygenase 1.
AB  - Guanosine, a guanine-based purine, is an extracellular signaling molecule that is
      released from astrocytes and shows neuroprotective effects in several in vivo and
      in vitro studies. Our group recently showed that guanosine presents antioxidant
      properties in C6 astroglial cells. The heme oxygenase 1 signaling pathway is
      associated with protection against oxidative stress. Azide, an inhibitor of the
      respiratory chain, is frequently used in experimental models to induce oxidative
      and nitrosative stress. Thus, the goal of this study was to investigate the
      effect of guanosine on azide-induced oxidative damage in C6 astroglial cells.
      Azide treatment of these cells resulted in several detrimental effects, including
      induction of cytotoxicity and mitochondrial dysfunction, increased levels of
      reactive oxygen/nitrogen species, inducible nitric oxide synthase expression and
      NADPH oxidase, decreased glutamate uptake and EAAC1 glutamate transporter
      expression, decreased glutathione (GSH) levels, and decreased activities of
      glutamine synthetase (GS), superoxide dismutase and catalase (CAT). The treatment
      also increased nuclear factor-kappaB activation and the release of
      proinflammatory cytokines tumor necrosis factor alpha and IL-1beta. Guanosine
      strongly prevented these effects, protecting glial cells against azide-induced
      cytotoxicity and modulating glial, oxidative and inflammatory responses through
      the activation of the heme oxygenase 1 pathway. These observations reinforce and
      support the role of guanosine as an antioxidant molecule against oxidative
      damage. Guanosine protects against azide-induced oxidative damage in C6
      astroglial cells. Azide-induced mitochondrial dysfunction (1); increased reactive
      oxygen species/reactive nitrogen species levels (2); decreased glutamate uptake
      (3), GS activity (4), GSH levels (5), and SOD (6) and CAT (7) activities;
      increased glutathione peroxidase (GPx) (8) and NADPH oxidase (9) activities and
      cellular superoxide levels (10); increased NF-kappaB activation (11), TNF-alpha
      and IL-1beta levels (12); and induced iNOS expression (13). Guanosine prevented
      these effects through the HO1 signaling pathway, thus our findings support the
      antioxidant effects of guanosine. 

PMID- 24673379
TI  - Pharmacogenetic considerations for acute lymphoblastic leukemia therapies.
AB  - INTRODUCTION: Advances in our understanding of the pathobiology of childhood
      acute lymphoblastic leukemia (ALL) have led to risk-targeted treatment regimens
      and remarkable improvement in survival rates. Still, up to 20% of patients
      experience treatment failure due to drug resistance. Treatment-related toxicities
      are often life-threatening and are the primary cause of treatment interruption,
      while ALL survivors may develop complications due to exposure to chemotherapy
      and/or irradiation during a vulnerable period of development. Different factors
      may contribute to variable treatment outcomes including patient genetics that has
      been shown to play important role. AREAS COVERED: This review summarizes
      candidate gene and genome-wide association studies that identified common
      polymorphisms underlying variability in treatment responses including a few
      studies addressing late effects of the treatment. Genetic variants influencing
      antileukemic drug effects or leukemic cell biology have been identified,
      including for example variants in folate-dependent enzymes, influx and efflux
      transporters, metabolizing enzymes, drug receptor or apoptotic proteins. EXPERT
      OPINION: Many pharmacogenetic studies have been conducted in ALL and a variety of
      potential markers have been identified. Yet more comprehensive insight into
      genome variations influencing drug responses is needed. Whole exome/genome
      sequencing, careful study design, mechanistic explanation of association found
      and collaborative studies will ultimately lead to personalized treatment and
      improved therapeutic and health outcomes.

PMID- 24673380
TI  - Family- and Neighborhood-Level Factors as Predictors of Conduct Problems in
      School among Young, Urban, Minority Children.
AB  - Minority children attending schools in urban socioeconomically disadvantaged
      neighborhoods are at high risk for conduct problems. Although a number of family
      and neighborhood characteristics have been implicated in the onset and
      progression of conduct problems, there remains incomplete understanding of the
      unique contributions of poverty-related factors early in development. This
      prospective study of 298 black public school children considered family- and
      neighborhood-level predictors of teacher-reported conduct problems from pre
      kindergarten through first grade. Results from multi-level analyses indicate that
      percentage of poor residents in a student's neighborhood made a robust
      independent contribution to the prediction of development of conduct problems,
      over and above family- and other neighborhood-level demographic factors. For
      children of single parents, the percentage of black residents in the neighborhood
      also predicted the development of conduct problems. School-based interventions to
      prevent conduct problems should consider impact for children at highest risk
      based on neighborhood poverty. 

PMID- 24673381
TI  - Video capsule endoscopy is successful and effective in outpatients with
      implantable cardiac devices.
AB  - BACKGROUND AND AIM: Implantable cardiac devices are a relative contraindication
      to video capsule endoscopy (VCE) because of concerns regarding interference. As a
      result of a lack of alternatives, some centers have adopted protocols to allow
      for VCE in these patients. There are minimal published descriptions of the
      gastrointestinal outcomes of these procedures. We investigated the completion
      rate and diagnostic yield of VCE carried out in outpatients with implantable
      cardiac devices. METHODS: We carried out a retrospective review of all VCE from
      April 2010 through March 2013 at our center. Patients that underwent VCE through
      a specialized protocol for outpatients with implantable cardiac devices were
      identified. The protocol used telemetry for cardiac monitoring during battery
      lifespan of the VCE. Demographic data, procedure indications, results and any
      procedural events were collected. RESULTS: Twenty-one patients met the study
      criteria, with 16 (76%) pacemakers, four (19%) implantable cardioverter
      defibrilla tors and one (5%) implantable hemodynamic monitor. Two (10%) devices
      were adjusted prior to VCE. Twenty (95%) were completed to the colon, with a
      median gastric transit time of 18 min and a small bowel transit time of 216 min.
      The procedure was diagnostic in 13 (62%) patients. One (5%) capsule retention
      event occurred. No cardiac events or video capture disturbances occurred.
      CONCLUSIONS: Video capsule endoscopy done on outpatients with implantable cardiac
      devices through a cardiac monitoring protocol resulted in a satisfactory
      completion rate and high diagnostic yield with no adverse cardiac events. A large
      prospective trial is needed to confirm these novel results.

PMID- 24673382
TI  - Patterns of coronary artery ectasia and short-term outcome in acute myocardial
      infarction.
AB  - OBJECTIVE: To assess the relationship between hematological inflammatory signs,
      cardiovascular risk (CV) factors and prognosis in patients presenting with acute
      myocardial infarction (AMI) and coronary artery ectasia (CAE). DESIGN: We
      investigated 3321 AMI patients who required urgent primary percutaneous
      intervention in two centres in the United Kingdom between January 2009 and August
      2012. Thirty patients with CAE were compared with 60 age- and gender-matched
      controls. Blood was collected within 2 h of the onset of chest pain. CV risk
      factors were assessed from the records. Major acute cardiac events and/or
      mortality (MACE) over 2 years were documented. RESULTS: CAE occurred in 2.7% and
      more often affected the right (RCA) (p = 0.001) and left circumflex artery (LCx)
      (0.0001). Culprit lesions were more frequently related to atherosclerosis in non
      CAE patients (p = 0.001). Yet, CV risk factors failed to differentiate between
      the groups, except diabetes, which was less frequent in CAE (p = 0.02). CRP was
      higher in CAE (p = 0.006), whereas total leucocyte, neutrophil counts and
      neutrophil/lymphocyte ratio (N/L ratio) were lower (p = 0.002, 0.002 and 0.032,
      respectively) than among non-CAE. This also was the case in diffuse versus
      localised CAE (p = 0.02, 0.008 and 0.03, respectively). The MACE incidence did
      not differ between CAE and non-CAE (p = 0.083) patients, and clinical management
      and MACE were unrelated to the inflammatory markers. CONCLUSION: In AMI, patients
      with CAE commonly have aneurysmal changes in RCA and LCx, and their inflammatory
      responses differ from those with non-CAE. These differences did not have
      prognostic relevance, and do not suggest different management.

PMID- 24673384
TI  - A United Kingdom-based economic evaluation of ranibizumab for patients with
      retinal vein occlusion (RVO).
AB  - OBJECTIVE: This study compares the cost-effectiveness of intravitreal ranibizumab
      vs observation and/or laser photocoagulation for treatment of macular edema
      secondary to retinal vein occlusion in a UK-based model. METHODS: A Markov model
      was constructed using transition probabilities and frequency of adverse events
      derived using data from the BRAVO, CRUISE, and HORIZON trials. Outcomes
      associated with treatments and health states were combined to predict overall
      health costs and outcomes for cohorts treated with each option. RESULTS: In
      branch retinal vein occlusion, ranibizumab produced a gain of 0.518 quality
      adjusted life years at an incremental cost of L8141, compared with laser
      photocoagulation. The incremental cost-effectiveness ratio was L15,710 per
      quality-adjusted life year, and the incremental cost per month free from
      blindness was L658. In central retinal vein occlusion, ranibizumab produced a
      gain of 0.539 quality-adjusted life years at an incremental cost of L9216,
      compared with observation only. The incremental cost-effectiveness ratio was
      L17,103, and the incremental cost per month free from blindness was L423.
      CONCLUSIONS: These incremental cost-effectiveness ratios are below the L20,000
      30,000 range typically accepted as a threshold for cost-effectiveness. This
      suggests that ranibizumab may be regarded as a cost-effective therapy for
      patients with macular edema secondary to retinal vein occlusion, relative to grid
      laser photocoagulation (for BRVO) and observation (for CRVO). Limitations include
      sparse data for utilities associated with the severity of visual impairment in
      the WSE in patients with RVO. A lack of direct comparative evidence between
      ranibizumab and the dexamethasone intravitreal implant for the treatment of BRVO
      and CRVO and the infeasibility of an indirect comparison due to significant
      heterogeneity in trial designs prevented the inclusion of this treatment as a
      comparator in the Markov model.

PMID- 24673383
TI  - Skin tumors with matrical differentiation: lessons from hair keratins, beta
      catenin and PHLDA-1 expression.
AB  - BACKGROUND: Pilomatricomas are tumors that emulate the differentiation of matrix
      cells of the hair follicle, showing cortical differentiation, with sequential
      expression of K35 and K31 keratins. Beta-catenin gene is frequently mutated in
      pilomatricoma, leading to beta-catenin nuclear accumulation, and to downstream
      expression of LEF1. Skin matrical tumors other than pilomatricoma are very rare,
      and comprise purely matrical tumors and focally matrical tumors. We aimed at
      studying cortical differentiation, beta-catenin pathway and expression of the
      follicular stem-cell marker PHLDA1 in a series of matrical tumors other than
      pilomatricoma. METHODS: In 36 prospectively collected tumors, K31, K35, CK17,
      LEF1, HOXC13, beta-catenin and PHLDA1 expressions were evaluated. Five
      pilomatricomas were used as controls. RESULTS: In 18 purely matrical tumors (11
      matrical carcinomas, 4 melanocytic matricomas, 3 matricomas) and 18 focally
      matrical tumors (11 basal cell carcinomas, 3 trichoepithelioma/trichoblastomas, 4
      others), sequential K35, HOXC13 and K31 expressions were found, indicating
      cortical differentiation. Germinative matrix cells were always CK17-, and showed
      nuclear beta-catenin accumulation, with LEF1 and PHLDA1 expressions. CONCLUSIONS:
      Nuclear beta-catenin and LEF1 expression was highly conserved in matrical tumors,
      and suggested a common tumorigenesis driven by Wnt pathway activation. PHLDA1 was
      consistently expressed in matrical tumors and in areas of matrical
      differentiation.

PMID- 24673385
TI  - Reduction of the pectoral spine and girdle in domesticated Channel catfish is
      likely caused by changes in selection pressure.
AB  - Locked pectoral spines of the Channel Catfish Ictalurus punctatus more than
      double the fish's width and complicate ingestion by gape-limited predators. The
      spine mates with the pectoral girdle, a robust structure that anchors the spine.
      This study demonstrates that both spine and girdle exhibit negative allometric
      growth and that pectoral spines and girdles are lighter in domesticated than in
      wild Channel Catfish. This finding could be explained by changes in selection
      pressure for spine growth during domestication or by an epigenetic effect in
      which exposure to predators in wild fish stimulates pectoral growth. We tested
      the epigenetic hypothesis by exposing domesticated Channel Catfish fingerlings to
      Largemouth Bass Micropterus salmoides predators for 13 weeks. Spines and girdles
      grow isometrically in the fingerlings, and regression analysis indicates no
      difference in proportional pectoral growth between control and predator-exposed
      fish. Therefore a change in selection pressure likely accounts for smaller
      pectoral growth in domesticated Channel Catfish. Decreasing spine growth in older
      fish suggests anti-predator functions are most important in smaller fish.
      Additionally, growth of the appendicular and axial skeleton is controlled
      differentially, and mechanical properties of the spine and not just its length
      are an important component of this defensive adaptation.

PMID- 24673386
TI  - Multicore magnetic nanoparticles (MMNPs) doped with Cs and FITC for the
      determination of biomarker in serum using ICP-MS.
AB  - Multicore magnetic nanoparticles (MMNPs) doped with Cs and FITC (Cs/FITC-doped
      MMNPs) were synthesized for the extraction and determination of biomarkers using
      inductively coupled plasma-mass spectrometry (ICP-MS). For demonstration, the
      MMNPs were used for magnetic separation to extract CA19-9 in serum
      nonspecifically, and the doped Cs was used as an internal standard for the
      ratiometric measurement of the tagged particle. This ratiometric method
      compensated for the particle loss in a magnetic separation and suppressed the
      signal fluctuation which increased the calibration linearity significantly. The
      obtained detection limit was 0.02 units/mL of CA19-9, which is more than 300
      times lower than that reported by the ICP-MS with element tagging and about 500
      fold improved compared to ELISA. 

PMID- 24673387
TI  - Magneto-structural correlations in a family of Fe(II)Re(IV)(CN)2 single-chain
      magnets: density functional theory and ab initio calculations.
AB  - Until now, the expressions of the anisotropic energy barriers Deltaxi and DeltaA,
      using the uniaxial magnetic anisotropy D, the intrachain coupling strength J, and
      the high-spin ground state S for single-chain magnets (SCMs) in the intermediate
      region between the Ising and the Heisenberg limits, were unknown. To explore this
      relationship, we used density functional theory and ab initio methods to obtain
      expressions of Deltaxi and DeltaA in terms of D, J, and S of six R4Fe(II)
      Re(IV)Cl4(CN)2 (R = diethylformamide (1), dibutylformamide (2), dimethylformamide
      (3), dimethylbutyramide (4), dimethylpropionamide (5), and diethylacetamide (6))
      SCMs in the intermediate region. The DeltaA value for compounds 1-3 was very
      similar to the magnetic anisotropic energy of a single Fe(II), while the value of
      Deltaxi was predicted using the exchange interaction of Fe(II) with the
      neighboring Re(IV), which could be expressed as 2JSReSFe. Similar to compounds 1
      3, the anisotropy energy barrier DeltaA of compounds 4 and 5 was also equal to
      (Di - Ei)SFe(2), but the correlation energy Deltaxi was closely equal to
      2JSReSFe(cos 98.4 - cos 180) due to the reversal of the spins on the opposite
      Fe(II). For compound 6, one unit cell of Re(IV)Fe(II) was regarded as a domain
      wall since it had two different Re(IV)-Fe(II) couplings. Thus, the Deltaxi of
      compound 6 was expressed as 4J"SRe1Fe1SRe2Fe2, where J" was the coupling constant
      of the neighboring unit cells of Re1Fe1 and Re2Fe2, and DeltaA was equal to the
      anisotropic energy barrier of one domain wall given by DRe1Fe1(S(2)Re1Fe1 - 1/4).

PMID- 24673388
TI  - Stereocontrolled synthesis of the tricyclic ABC ring system of daphnicyclidin A.
AB  - An enantiocontrolled synthesis pathway has been developed to provide formation of
      tricyclic amine 7, representing the ABC ring system of the complex alkaloid
      daphnicyclidin A (1). Our efforts describe preparation of the Z-hexahydro-(1H)
      azocine 29 and cyclization to construct the novel 4-azabicyclo[5.3.2]dodecane 31.
      Transannular reductive amination following the deprotection of 31 gave the
      desired tertiary amine 7. 

PMID- 24673389
TI  - A pediatric case of multiple palisaded encapsulated neuromas of the palms and
      soles.
AB  - Palisaded encapsulated neuroma (PEN) usually presents as a solitary, skin-colored
      papule on the face in middle-aged adults. We present a rare pediatric case of
      multiple PEN of the palms and soles. DNA analysis of the RET proto-oncogene in
      our patient showed no mutations in exons 13, 15, and 16. 

PMID- 24673390
TI  - The nickel dose-response relationship by filaggrin genotype (FLG).
AB  - BACKGROUND: On skin contact, nickel accumulates in the stratum corneum, where it
      is probably bound to proteins and amino acids. One probable contributor is
      filaggrin, which binds nickel avidly. Filaggrin gene (FLG) null mutations lead to
      a complete lack of filaggrin production from the affected allele, and have been
      associated with an increased risk of nickel contact sensitization in German and
      Danish adults. OBJECTIVES: To investigate whether the experimental nickel
      elicitation threshold level differed between heterozygous FLG mutation and non
      mutation carriers. METHOD: Thirteen nickel-sensitized female patients, seven
      heterozygous mutation carriers and six non-mutation carriers (genotyped for
      R501X, 2282del4, or R2447X), were patch tested and performed a repeated open
      application test (ROAT) with a nickel sulfate dilution series. Logistic threshold
      dose-response analyses were used to test for differences between the two groups.
      RESULTS: No difference was found in the dose-response relationship between FLG
      mutation and non-mutation carriers. CONCLUSIONS: On the basis of this small
      patient study, it appears that the elicitation threshold level for nickel is
      independent of FLG null mutation single-allele carrier status.

PMID- 24673391
TI  - Aligning experimental and theoretical anisotropic B-factors: water models, normal
      mode analysis methods, and metrics.
AB  - The strength of X-ray crystallography in providing the information for protein
      dynamics has been under appreciated. The anisotropic B-factors (ADPs) from high
      resolution structures are invaluable in studying the relationship among
      structure, dynamics, and function. Here, starting from an in-depth evaluation of
      the metrics used for comparing the overlap between two ellipsoids, we applied
      normal-mode analysis (NMA) to predict the theoretical ADPs and then align them
      with experimental results. Adding an extra layer of explicitly treated water on
      protein surface significantly improved the energy minimization results and better
      reproduced the anisotropy of experimental ADPs. In comparing experimental and
      theoretical ADPs, we focused on the overlap in shape, the alignment of dominant
      directions, and the similarity in magnitude. The choices of water molecules, NMA
      methods, and the metrics for evaluating the overlap of ADPs determined final
      results. This study provides useful information for exploring the physical basis
      and the application potential of experimental ADPs. 

PMID- 24673392
TI  - Design, Synthesis, Acaricidal Activity, and Mechanism of Oxazoline Derivatives
      Containing an Oxime Ether Moiety.
AB  - Two series of novel 2,4-diphenyl-1,3-oxazolines containing an oxime ether moiety
      were designed and synthesized via the key intermediate N-(2-chloro-1-(p
      tolyl)ethyl)-2,6-difluorobenzamide. The bioassay results showed that the target
      compounds with an oxime ether substituent at the para position of 4-phenyl
      exhibited excellent acaricidal activity against Tetranychus cinnabarinus in the
      laboratory. Moreover, all of the target compounds had much higher activities than
      etoxazole, as the ovicidal and larvicidal activities of the target compounds I-a
      I-l and II-a-II-n against T. cinnabarinus were all over 90% at 0.001 mg L-1, but
      etoxazole gave only 30% and 40% respectively at the same concentration. The
      activity order of compounds with regard to acaricidal activity in vivo was almost
      consistent with their affinity activity with sulfonylurea receptor (SUR) of
      Blattella germanica in vitro, hence, it was supposed that the acaricidal
      mechanism of action of the target compounds was that they can bind with the site
      of SUR and therefore inhibit chitin synthesis. Moreover, the eminent effect of
      the compound II-l, [2-(trifluoromethyl)benzaldehyde O-(4-(2-(2,6-difluorophenyl)
      4,5-dihydrooxazol-4-yl)benzyl) oxime], against Panonychus citri and T.
      cinnabarinus in the field indicated that II-l exhibited a promising application
      prospect as a new candicate for controlling spider mites in the field.

PMID- 24673393
TI  - Protein removal from waste brines generated during ham salting through
      acidification and centrifugation.
AB  - The salting step in food processes implies the production of large quantities of
      waste brines, having high organic load, high conductivity, and other pollutants
      with high oxygen demand. Direct disposal of the residual brine implies
      salinization of soil and eutrophication of water. Since most of the organic load
      of the waste brines comes from proteins leaked from the salted product,
      precipitation of dissolved proteins by acidification and removal by
      centrifugation is an operation to be used in waste brine cleaning. The aim of
      this study is optimizing the conditions for carrying out the separation of
      proteins from waste brines generated in the pork ham salting operation, by
      studying the influence of pH, centrifugal force, and centrifugation time. Models
      for determining the removal of proteins depending on the pH, centrifugal force,
      and time were obtained. The results showed a high efficacy of the proposed
      treatment for removing proteins, suggesting that this method could be used for
      waste brine protein removal. The best pH value to be used in an industrial
      process seems to be 3, while the obtained results indicate that almost 90% of the
      proteins from the brine can be removed by acidification followed by
      centrifugation. A further protein removal from the brine should have to be
      achieved using filtrating techniques, which efficiency could be highly improved
      as a consequence of the previous treatment through acidification and
      centrifugation. PRACTICAL APPLICATION: Waste brines from meat salting have high
      organic load and electrical conductivity. Proteins can be removed from the waste
      brine by acidification and centrifugation. The total protein removal can be up to
      90% of the initial content of the waste brine. Protein removal is highly
      dependent on pH, centrifugation rate, and time.

PMID- 24673394
TI  - Organocatalytic access to enantioenriched dihydropyran phosphonates via an
      inverse-electron-demand hetero-Diels-Alder reaction.
AB  - The enantioselective inverse-electron-demand hetero-Diels-Alder reaction of the
      remote olefin functionality in dienamines has been developed by the simultaneous
      activation of alpha,beta-unsaturated aldehydes and acyl phosphonates. The dual
      activation is based on an organocatalyst that activates both the alpha,beta
      unsaturated aldehyde, through dienamine formation, and the acyl phosphonate by
      hydrogen-bonding. The enantioselective reaction results in the formation of
      dihydropyran frameworks with three contiguous stereogenic centers. Different
      substitution patterns are possible for both the heterodiene and the dienophile,
      and the target products are obtained in good yields and up to 92% ee. The
      potential of the reaction is demonstrated by transformation of the products into
      valuable and complex synthons. 

PMID- 24673395
TI  - Orofacial esthetics and dental anxiety: associations with oral and psychological
      health.
AB  - OBJECTIVE: Severe dental anxiety (DA) is associated with both oral health and
      psychosocial consequences in what has been described as a vicious circle of DA.
      The aim of this study was to investigate self-rated orofacial esthetics in
      patients with DA and its relationship to psychological and oral health. MATERIALS
      AND METHODS: A consecutive sample of 152 adult patients who were referred or self
      referred to a specialized dental anxiety clinic filled out the Orofacial Esthetic
      Scale (OES) as well as measurements on DA, self-rated oral health and general
      anxiety and depression. Clinical measures of dental status were also obtained.
      RESULTS: Compared with the general population, patients with DA had lower ratings
      of satisfaction on all aspects of their orofacial esthetics, which included the
      teeth, gingiva, mouth and face, as well as a global orofacial assessment.
      Furthermore, the perception of the orofacial appearance was related both to
      dental status and self-rated oral health, as well as to general anxiety and
      depression. The level of dissatisfaction with the orofacial appearance was
      similar for both genders, but women reported more regular dental care and better
      dental status. CONCLUSIONS: The results of this study clearly show less
      satisfaction with dental and facial appearance in patients with DA, and that the
      self-rating of orofacial esthetics is related to both oral and psychological
      health. The OES can be used to assess orofacial esthetics in patients with DA.

PMID- 24673396
TI  - Significant reduction in red blood cell transfusions in a general hospital after
      successful implementation of a restrictive transfusion policy supported by
      prospective computerized order auditing.
AB  - BACKGROUND: Our hospital transfusion policy was recently revised to recommend
      single-unit red blood cell transfusion (RBC TXN) for nonbleeding inpatients when
      the hemoglobin (Hb) level is not more than 7 g/dL. Our computerized provider
      order entry system was reconfigured to provide real-time decision support using
      prospective computerized order auditing based on the most recent Hb level and to
      remove the single-click ordering option for 2-unit RBC TXNs to enhance
      compliance. This study was undertaken to assess the impact of these changes on
      hospital transfusion practice. STUDY DESIGN AND METHODS: This study analyzed the
      total number of transfusion events, proportion of single and 2-unit transfusions
      and the Hb transfusion trigger in the preimplementation period (October 2011
      March 2012) compared to the postimplementation period (October 2012-March 2013).
      RESULTS: In the postimplementation period the total number of RBC units
      transfused/1000 patient-days decreased from 60.8 to 44.2 (p < 0.0001). The
      proportion of 2-unit TXNs decreased from 47% to 15% (p < 0.0001). We also
      observed significant decreases in pretransfusion Hb triggers. CONCLUSION:
      Implementation of restrictive transfusion policy supported by prospective
      computerized order auditing has resulted in significantly decreased RBC
      utilization at our institution.

PMID- 24673397
TI  - Wettability of azobenzene self-assembled monolayers.
AB  - The wettability properties of azobenzene self-assembled monolayers (SAMs), in the
      trans and cis forms, are investigated herein by classical Molecular Dynamics
      simulations of validated assembly structures described with a dedicated force
      field. The two different methodologies used for the calculation of the contact
      angle, one based on the Young's equation and the other on geometrical models,
      have provided a consistent description of the SAMs wettability in line with
      available experimental results. Furthermore, we provide an atomistic description
      of the first layers of water molecules at the solvent-SAM interface, which
      rationalizes the wettability difference between the cis- and trans-SAMs. 

PMID- 24673398
TI  - Salvage therapy with pegylated liposomal doxorubicin, bortezomib,
      cyclophosphamide, and dexamethasone in relapsed/refractory myeloma patients.
AB  - OBJECTIVES: In vitro studies have shown synergistic anti-myeloma effects of
      bortezomib combined with alkylating agents or anthracycline. We tested safety and
      efficacy of the combination of bortezomib, doxorubicin cyclophosphamide, and
      dexamethasone (ABCD) in the treatment of relapsed/refractory myeloma. METHODS:
      ABCD consisted of bortezomib given intravenous (IV) at dosage 1.3 mg/m(2) ,
      dexamethasone 40 mg IV on days 1, 4, 8, and 15, pegylated liposomal doxorubicin
      (PLD) 20 mg IV on days 1 and 15, plus cyclophosphamide 100 mg/d per os for 15 d.
      Between January 2008 and February 2009, 24 patients received a median of four 28
      d ABCD cycles (range 1-6). All patients had been already treated with a median of
      two previous lines of treatment (range 1-6): 38% were resistant to previous
      therapies and 62% were relapsed. RESULTS: Clinical response was observed in 12
      patients (50%), including 29% of very good partial remissions or better. Side
      effects included hematological toxicity (31% any grade), grades 3-4
      thrombocytopenia (9%), grades 3-4 anemia (17%). Non-hematological toxicity
      affected 32% of administered cycles and included gastrointestinal disturbances
      (54%), peripheral neuropathy (8%), and infections (8%). After a median follow-up
      of 21.5 months (range 2-44 months), median of progression-free survival (PFS) was
      8.7 months and median overall survival was 22.5 months. Achieving at least
      partial response within the second cycle was associated with a better PFS (19.5
      months vs. 3.5 months), P = 0.03, HR 0.35 (CI 95% 0.13-0.90). CONCLUSION: ABCD is
      safe and effective for relapsed/refractory MM subjects previously treated with
      novel agents.

PMID- 24673399
TI  - The association between therapeutic outcomes and VEGF G-1154A and C-936T gene
      polymorphisms in patients with glomerulonephritis.
AB  - BACKGROUND: In this present study, we aimed to investigate the association
      between therapeutic outcomes and vascular endothelial growth factor (VEGF) G
      1154A and C-936T gene polymorphisms in patients with glomerulonephritis. METHODS:
      Thirty-eight patients with glomerulonephritis diagnosed by renal biopsy were
      included to the study. All patients had proteinuria at least 1 gram (g)/day in
      urine analysis. At the end of a yearly therapy, patients with proteinuria less
      than 0.5 g/day were accepted as in complete remission and they were termed as
      group 1. The patients with proteinuria over 0.5 g/day were accepted as in no
      remission and they were termed as group 2. RESULTS: The mean age of patients in
      group 1 and group 2 was 35.88 +/- 13.80 years and 37.30 +/- 13.89 years,
      respectively. There were nine (50%) male and nine (50%) female patients in group
      1. In group 2, seven (35%) male and 13 (65%) female patients were present.
      Although VEGF G-1154A (GG) gene polymorphism was found in 55% of group 2
      patients, and 22.2% of group 1 patients, but the differences did not reach
      statistical significance. There were no statistical differences between groups in
      terms of other gene polymorphisms. Namely, we obtained no statistical differences
      between therapeutic outcomes and gene polymorphisms. CONCLUSIONS: There is a
      significant difference between groups in terms of VEGF G-1154A (GG) gene
      polymorphism, but the minority of the patient population has led to not to reach
      statistical significance. So, this gene polymorphism has to be investigated in
      larger studies.

PMID- 24673400
TI  - Xylaolide A, a new lactone from the fungus Xylariaceae sp. DPZ-SY43.
AB  - Chemical investigation of the fungus Xylariaceae sp. DPZ-SY43 has led to the
      isolation of a new compound, xylaolide A (1) together with three known compounds
      (2-4). The structures were established by analysing the spectroscopic data.
      Compound 1 was evaluated for its cytotoxicity. 

PMID- 24673401
TI  - Camelid-derived heavy-chain nanobody against Clostridium botulinum neurotoxin E
      in Pichia pastoris.
AB  - Botulinum neurotoxins (BoNTs) result in severe and often fatal disease, botulism.
      Common remedial measures such as equine antitoxin and human botulism
      immunoglobulin in turn are problematic and time-consuming. Therefore, diagnosis
      and therapy of BoNTs are vital. The variable domain of heavy-chain antibodies
      (VHH) has unique features, such as the ability to identify and bind specifically
      to target epitopes and ease of production in bacteria and yeast. The Pichia
      pastoris is suitable for expression of recombinant antibody fragments. Disulfide
      bond formation and correct folds of protein with a high yield are some of the
      advantages of this eukaryotic host. In this study, we have expressed and purified
      the camelid VHH against BoNT/E in P. pastoris. The final yield of P. pastoris
      expressed antibody was estimated to be 16 mg/l, which is higher than that
      expressed by Escherichia coli. The nanobody expressed in P. pastoris neutralized
      4LD50 of the BoNT/E upon i.p. injection in 25% of mice. The nanobody expressed in
      E. coli extended the mice's survival to 1.5-fold compared to the control. This
      experiment indicated that the quality of expressed protein in the yeast is
      superior to that of the bacterial expression. Favorable protein folding by P.
      pastoris seems to play a role in its better toxin-binding property. 

PMID- 24673403
TI  - Late-onset onchocercal skin disease among Ethiopian immigrants.
AB  - BACKGROUND: Onchocerciasis is an infectious disease caused by the filaria
      Onchocerca volvulus. Very little is known regarding onchocerciasis imported from
      endemic to nonendemic areas. OBJECTIVES: To evaluate pruritic dermatitis
      simulating atopic dermatitis in Ethiopian immigrants in Israel. PATIENTS AND
      METHODS: A retrospective study of 27 Ethiopian immigrants to Israel was
      conducted. Demographics and clinical and laboratory data were collected. RESULTS:
      Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The
      average age at referral was 29 years. All of the patients emigrated from Kuwara,
      Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin
      (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation
      was a combination of lichenified onchodermatitis with atrophy and depigmentation
      (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were
      treated with a single administration of oral ivermectin 200 MUg mg(-1). Thirteen
      patients responded to the treatment. CONCLUSIONS: Immigrants from endemic regions
      to developed countries presenting with pruritic diseases, especially those with a
      clinical picture suggestive of atopic dermatitis, should be evaluated for
      possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost
      treatment, should be considered even in the absence of a proven disease.
      Physicians should have a high index of suspicion in patients with the
      corresponding residential history.

PMID- 24673404
TI  - A possible relationship between metal implant-induced intralymphatic
      histiocytosis and the concept of the immunocompromised district.

PMID- 24673402
TI  - A gluten-free diet lowers NKG2D and ligand expression in BALB/c and non-obese
      diabetic (NOD) mice.
AB  - The interplay between diet and immune parameters which could affect type 1
      diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal up
      regulation of the activating receptor natural killer group 2D (NKG2D) (CD314) and
      its ligands is a hallmark of coeliac disease. However, the direct effect of
      gluten on NKG2D expression is not known. We studied, by fluorescence activated
      cell sorter (lymphoid tissues) and reverse transcription-quantitative polymerase
      chain reaction (intestine and pancreatic islets), if a gluten-free diet (GF diet)
      from 4 weeks of age or a gluten-free diet introduced in breeding pairs (SGF
      diet), induced changes in NKG2D expression on DX5(+) (CD49b) natural killer (NK)
      cells, CD8(+) T cells and in intestinal and islet levels of NKG2D and ligands in
      BALB/c and non-obese diabetic (NOD) mice. Gluten-free NOD mice had lower
      insulitis (P < 0.0001); reduced expression of NKG2D on DX5(+) NK cells in spleen
      and auricular lymph nodes (P < 0.05); and on CD8(+) T cells in pancreas
      associated lymph nodes (P = 0.04). Moreover, the level of CD71 on DX5(+) NK cells
      and CD8(+) T cells (P < 0.005) was markedly reduced. GF and SGF mice had reduced
      expression of NKG2D and DX5 mRNA in intestine (P < 0.05). Differences in
      intestinal mRNA expression were found in mice at 8, 13 and 20 weeks. Intestinal
      expression of NKG2D ligands was reduced in SGF mice with lower expression of all
      ligands. In isolated islets, a SGF diet induced a higher expression of specific
      NKG2D ligands. Our data show that a gluten-free diet reduces the level of NKG2D
      and the expression of NKG2D ligands. These immunological changes may contribute
      to the lower T1D incidence associated with a gluten-free diet. 

PMID- 24673405
TI  - Considerations for rare variants in drug metabolism genes and the clinical
      implications.
AB  - INTRODUCTION: Large-scale whole genome and exome resequencing studies have
      revealed that humans have a high level of deleterious rare variation, which has
      important implications for the design of future pharmacogenetics studies. AREAS
      COVERED: Current pharmacogenetic guidelines focus on the implementation of common
      variation into dosing guidelines. However, it is becoming apparent that rare
      variation may also play an important role in differential drug response. Current
      sequencing technologies offer the opportunity to examine rare variation, but
      there are many challenges associated with such analyses. Nonetheless, if a
      comprehensive picture of the role that genetic variants play in treatment
      outcomes is to be obtained, it will be necessary to include the entire spectrum
      of variation, including rare variants, into pharmacogenetic research. EXPERT
      OPINION: In order to implement pharmacogenetics in the clinic, patients should be
      genotyped for clinically actionable pharmacogenetic variants and patients
      responding unfavourably to treatment after pharmacogenetics-based dosing should
      be identified and resequenced to identify additional functionally relevant
      variants, including rare variants. All derived information should be added to a
      central database to allow for the updating of existing dosing guidelines. By
      routinely implementing such strategies, pharmacogenetics-based treatment
      guidelines will continue to improve.

PMID- 24673406
TI  - Correlation of OAS1 gene polymorphism at exon 7 splice accepter site with
      interferon-based therapy of HCV infection in Pakistan.
AB  - The most useful treatment for HCV infection worldwide is peg-interferon plus
      ribavirin, although the response varies from person to person. Hence, host
      genetics are significantly involved in the treatment response to HCV infection.
      The 2'-5' oligoadenylate synthetase (OAS) is one of the most important components
      of the immune system having significant antiviral functions. The aim of this
      study was to investigate the role of single nucleotide polymorphism (SNP) at the
      exon 7 splice acceptor site (SAS) of OAS1 to interferon-based therapy of HCV
      infection. OAS1 genotyping was performed in 140 HCV patients by restriction
      fragment length polymorphism polymerase chain reaction method (RFLP-PCR). These
      patients were enrolled for the study in 2010-2013. OAS1 SNP was also established
      in 120 healthy controls. Correlation of HCV genotypes, OAS1 SNP, and other
      factors with response to interferon therapy were statistically analyzed by SPSS
      13 software. There were no significant differences in the distribution of OAS1
      genotypes between healthy and patients subjects. The distribution of AG and AA
      genotypes of OAS1 genotypes between sustained virological responders (SVRs) and
      the non-responders (NRs) group were also comparable. However, Pearson chi square
      analysis indicated that the patients possessing a GG genotype of the OAS1 gene at
      exon 7 SAS demonstrated significantly positive association with treatment
      response to HCV infection (p=0.039). This study determined that SNP at exon 7 SAS
      of OAS1 was significantly associated with response to interferon-based therapy of
      HCV infection in our population.

PMID- 24673407
TI  - Between thought and expression, a magnetoencephalography study of the "tip-of-the
      tongue" phenomenon.
AB  - "Tip-of-the-tongue" (TOT) is the phenomenon associated with the inaccessibility
      of a known word from memory. It is universally experienced, increases in
      frequency with age, and is most common for proper nouns. It is a good model for
      the symptom of anomia experienced much more frequently by some aphasic patients
      following brain injury. Here, we induced the TOT state in older participants
      while they underwent brain scanning with magnetoencephalography to investigate
      the changes in oscillatory brain activity associated with failed retrieval of
      known words. Using confrontation naming of pictures of celebrities, we
      successfully induced the TOT state in 29% of trials and contrasted it with two
      other states: "Know" where the participants both correctly recognized the
      celebrity's face and retrieved their name and "Don't Know" when the participants
      did not recognize the celebrity. We wished to test Levelt's influential model of
      speech output by carrying out two analyses, one epoching the data to the point in
      time when the picture was displayed and the other looking back in time from when
      the participants first articulated their responses. Our main findings supported
      the components of Levelt's model, but not their serial activation over time as
      both semantic and motor areas were identified in both analyses. We also found
      enduring decreases in the alpha frequency band in the left ventral temporal
      region during the TOT state, suggesting ongoing semantic search. Finally, we
      identified reduced beta power in classical peri-sylvian language areas for the
      TOT condition, suggesting that brain regions that encode linguistic memories are
      also involved in their attempted retrieval. 

PMID- 24673408
TI  - Persistent spatial information in the FEF during object-based short-term memory
      does not contribute to task performance.
AB  - We previously reported the existence of a persistent spatial signal in the FEF
      during object-based STM. This persistent activity reflected the location at which
      the sample appeared, irrespective of the location of upcoming targets. We
      hypothesized that such a spatial signal could be used to maintain or enhance
      object-selective memory activity elsewhere in cortex, analogous to the role of a
      spatial signal during attention. Here, we inactivated a portion of the FEF with
      GABAa agonist muscimol to test whether the observed activity contributes to
      object memory performance. We found that, although RTs were slowed for saccades
      into the inactivated portion of retinotopic space, performance for samples
      appearing in that region was unimpaired. This contrasts with the devastating
      effects of the same FEF inactivation on purely spatial working memory, as
      assessed with the memory-guided saccade task. Thus, in a task in which a
      significant fraction of FEF neurons displayed persistent, sample location-based
      activity, disrupting this activity had no impact on task performance. 

PMID- 24673409
TI  - Stepwise unfolding of bovine and human serum albumin by an anionic surfactant: an
      investigation using the proton transfer probe norharmane.
AB  - Interactions of the anionic surfactant sodium dodecyl sulfate (SDS) with the
      transport proteins bovine serum albumin (BSA) and human serum albumin (HSA) have
      been divulged using an external photoinduced proton transfer probe, norharmane
      (NHM). Steady-state fluorometry, time-resolved measurements, micropolarity
      analysis, circular dichroism (CD), and isothermal titration calorimetry (ITC)
      have been exploited for the study. With the gradual addition of SDS to the probe
      bound proteins, the fluorometric responses of the different prototropic species
      of NHM exhibit an opposite pattern as to that observed while NHM binds to the
      proteins. The study reveals a sequential unfolding of the serum proteins with the
      gradual addition of SDS. ITC measures the heat changes associated with each step
      of the unfolding. ITC experiments, carried out at two different pH's, elucidate
      the nature of interaction between SDS and the two serum proteins. At a very high
      concentration of SDS, the external probe (NHM) is found to be dislodged from the
      protein environments to bind to the SDS micellar medium. 

PMID- 24673410
TI  - Hydrogen sulfide protects blood-brain barrier integrity following cerebral
      ischemia.
AB  - By using two structurally unrelated hydrogen sulfide (H2 S) donors 5-(4
      methoxyphenyl) -3H-1, 2-dithiole-3-thione (ADT) and sodium hydrosulfide (NaHS),
      this study investigated if H2 S protected blood-brain barrier (BBB) integrity
      following middle cerebral artery occlusion (MCAO). ICR mice underwent MCAO and
      received H2 S donors at 3 h after reperfusion. Infarction, neurological scores,
      brain edema, Evans blue (EB) extravasation, and tight junction protein expression
      were examined at 48 h after MCAO. We also investigated if ADT protected BBB
      integrity by suppressing post-ischemic inflammation-induced Matrix
      Metalloproteimase-9 (MMP9) and Nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase (NOX). ADT increased blood H2 S concentrations, decreased
      infarction, and improved neurological deficits. Particularly, ADT reduced EB
      extravasation, brain edema and preserved expression of tight junction proteins in
      the ischemic brain. NaHS also increased blood H2 S levels and reduced EB
      extravasation following MCAO. Moreover, ADT inhibited expression of pro
      inflammatory markers induced Nitric Oxide Synthase (iNOS) and IL-1beta while
      enhanced expression of anti-inflammatory markers arginase 1 and IL-10 in the
      ischemic brain. Accordingly, ADT attenuated ischemia-induced expression and
      activity of MMP9. Moreover, ADT reduced NOX-4 mRNA expression, NOX activity, and
      inhibited nuclear translocation of Nuclear Factor Kappa-B (NF-kappaB) in the
      ischemic brain. In conclusion, H2 S donors protected BBB integrity following
      experimental stroke possibly by acting through NF-kappaB inhibition to suppress
      neuroinflammation induction of MMP9 and NOX4-derived free radicals. To determine
      H2 S effects on blood-brain barrier (BBB) disruption following stroke, we used
      two structurally unrelated H2 S donors ADT and NaHS. Both ADT and NaHS remarkably
      protected BBB integrity following experimental stroke. The slow-releasing donor
      ADT also reduced post-ischemic inflammation-induced expression and activity of
      MMP9 and NOX4 in the ischemic brain possibly by inhibiting NF-kappaB activation.

PMID- 24673411
TI  - Single-step total fractionation of single-wall carbon nanotubes by countercurrent
      chromatography.
AB  - Development of simple processes to fractionate synthetic mixtures of single-wall
      carbon nanotubes (SWCNTs) into individual species is crucial to many
      applications. Existing methods for single-chirality SWCNT purification are
      cumbersome, often requiring multiple steps and different conditions for different
      species. Here, we report a method to achieve total fractionation of a synthetic
      SWCNT mixture by countercurrent chromatography, resulting in purification of many
      single-chirality SWCNT species in a single run. This method is based on a tunable
      partition of sodium deoxycholate dispersed SWCNTs in a polyethylene
      glycol/dextran aqueous two-phase system. By running the mobile phase with 0.02%
      of sodium deoxycholate and a gradient of sodium dodecyl sulfate from 0.1% to 0.7%
      (w/w), we observe clear diameter-dependent elution, with ~ 90% total recovery.
      Among all the fractions collected, a number of them are enriched in single
      chirality (9,4), (7,5), (7,6), (8,3), (6,5) species, while most of the remaining
      ones contain no more than 2-3 major species. We also observe strong (n,m)
      dependent elution peak width due to the enantiomer-resolved partition. These
      results demonstrate countercurrent chromatography (CCC) as an effective way to
      obtain high purity (n, m) species, and suggest the potential of CCC as an
      analytical tool for chirality distribution mapping of synthetic SWCNT mixtures. 

PMID- 24673412
TI  - Association between a 27-bp variable number of tandem repeat polymorphism in
      intron 4 of the eNOS gene and risk for diabetic retinopathy Type 2 diabetes
      mellitus: a meta-analysis.
AB  - PURPOSE: Imbalance in the production of endothelial nitric oxide synthase (eNOS),
      which plays an essential role in retinal vascular function, can lead to the
      development of diabetic retinopathy (DR). To thoroughly address this issue, we
      performed an updated meta-analysis to evaluate the association between the eNOS
      27VNTR (4b/4a) polymorphism and DR in type 2 diabetes mellitus (T2DM). METHODS: A
      search was conducted of PubMed and Chinese language (WanFang) databases through 3
      March 2013. Data were retrieved in a systematic manner and analyzed using Stata
      Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs)
      were used to assess the strength of associations. RESULTS: Based on the search
      criteria for DR susceptibility related to the 27VNTR (4b/4a) polymorphism of the
      eNOS gene, 16 case-control studies (15 articles), comprising 3227 T2DM patients
      with DR and 3437 T2DM patients without DR, were retrieved. Although no
      significant associations were uncovered in either the overall analysis or DR
      subtype groups, a decreased association was detected between the African-
      (allelic contrast: OR = 0.75, 95% CI = 0.65-0.88) or population-based (PB)
      studies (dominant genetic model: OR = 0.91, 95% CI = 0.83-0.98) and the eNOS
      27VNTR (4b/4a) polymorphism. Stratification according to average duration of DM
      revealed that T2DM patients with histories of >10 years had an elevated
      susceptibility to DR compared with those with histories of shorter durations
      (homozygote comparison: OR = 1.67, 95% CI = 1.09-2.58). CONCLUSIONS: The present
      meta-analysis suggests that the eNOS 27VNTR (4b/4a) polymorphism potentially
      decreases the risk of developing DR in T2DM African individuals. The higher
      degree of susceptibility in patients with longer (>10 years) durations of DM is
      indicative of the involvement of a gene-environment interaction in determining
      the risk for DR. Further studies, based on larger sample sizes and additional
      gene-environment interactions, should be conducted to elucidate the role of eNOS
      gene polymorphisms, especially 27VNTR (4b/4a), in the risk for DR.

PMID- 24673413
TI  - Comparison of chemical and heating methods to enhance latent fingerprint deposits
      on thermal paper.
AB  - A comparison is made of proprietary methods to develop latent fingerprint
      deposits on the inked side of thermal paper using either chemical treatment
      (Thermanin) or the application of heat to the paper (Hot Print System). Results
      with a trial of five donors show that the application of heat produces
      statistically significantly more fingerprint ridge detail than the chemical
      treatment for both fingerprint deposits aged up to 4 weeks and for a nine
      sequence depletion series. Subjecting the thermal paper to heat treatment with
      the Hot Print System did not inhibit subsequent ninhydrin chemical development of
      fingerprint deposits on the noninked side of the paper. A further benefit of the
      application of heat is the rapid development of fingerprint deposits (less than a
      minute) compared with up to 12 h for the Thermanin chemical treatment.

PMID- 24673414
TI  - Quantitative genetic modeling and inference in the presence of nonignorable
      missing data.
AB  - Natural selection is typically exerted at some specific life stages. If natural
      selection takes place before a trait can be measured, using conventional models
      can cause wrong inference about population parameters. When the missing data
      process relates to the trait of interest, a valid inference requires explicit
      modeling of the missing process. We propose a joint modeling approach, a shared
      parameter model, to account for nonrandom missing data. It consists of an animal
      model for the phenotypic data and a logistic model for the missing process,
      linked by the additive genetic effects. A Bayesian approach is taken and
      inference is made using integrated nested Laplace approximations. From a
      simulation study we find that wrongly assuming that missing data are missing at
      random can result in severely biased estimates of additive genetic variance.
      Using real data from a wild population of Swiss barn owls Tyto alba, our model
      indicates that the missing individuals would display large black spots; and we
      conclude that genes affecting this trait are already under selection before it is
      expressed. Our model is a tool to correctly estimate the magnitude of both
      natural selection and additive genetic variance. 

PMID- 24673415
TI  - Endocrine mucin-producing sweat gland carcinoma occurring on extra-facial site: a
      case report.
AB  - Cutaneous endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a very rare
      low-grade malignant neoplasm analogous to the mammary solid-papillary carcinoma.
      It frequently expresses neuroendocrine markers and may show mucinous
      differentiation. Although the nodules are circumscribed, myoepithelial cells
      cannot be showed in most cases and about half of the cases are associated with
      invasive mucinous carcinoma. Hence, it has been suggested to be invasive and the
      precursor lesion of some primary cutaneous mucinous carcinomas. After being
      recognized as a distinct entity, all cases reported to date occurred either in
      the periocular region or on the cheek. Two thirds of the patients were female.
      Herein we present an unusual case of in situ EMPSGC on the chest wall skin of a
      middle-aged man. 

PMID- 24673416
TI  - Genomic architecture of histone 3 lysine 27 trimethylation during late ovine
      skeletal muscle development.
AB  - The ruminant developmental transition from late foetus to lamb is associated with
      marked changes in skeletal muscle structure and function that reflect programming
      for new physiological demands following birth. To determine whether epigenetic
      changes are involved in this transition, we investigated the genomic architecture
      of the chromatin modification, histone 3 lysine 27 trimethylation (H3K27me3),
      which typically regulates early life developmental processes; however, its role
      in later life processes is unclear. Chromatin immunoprecipitation coupled with
      next-generation sequencing was used to map H3K27me3 nucleosomes in ovine
      longissimus lumborum skeletal muscle at 100 days of gestation and 12 weeks post
      partum. In both states, H3K27me3 modification was associated with genes,
      transcription start sites and CpG islands and with transcriptional silencing. The
      H3K27me3 peaks consisted of two major categories, promoter specific and regional,
      with the latter the dominant feature. Genes encoding homeobox transcription
      factors regulating early life development and genes involved in neural functions,
      particularly gated ion channels, were strongly modified by H3K27me3. Gene
      promoters differentially modified by H3K27me3 in the foetus and lamb were
      enriched for gated ion channels, which may reflect changes in neuromuscular
      function. However, most modified genes showed no changes, indicating that
      H3K27me3 does not have a large role in late muscle maturation. Notably,
      promyogenic transcription factors were strongly modified with H3K27me3 but showed
      no differences between the late gestation foetus and lamb, likely reflecting
      their lack of involvement in the myofibre fusion process occurring in this
      transition. H3K27me3 is a major architectural feature of the epigenetic landscape
      of ruminant skeletal muscle, and it comments on gene transcription and gene
      function in the context of late skeletal muscle development.

PMID- 24673417
TI  - Use of cast post-and-cores for the alteration of crown position for the
      esthetically compromised patient.
AB  - The authors describe the use of cast post-and-cores, which allow a change in
      position of the clinical crown to permit the fabrication of two fixed partial
      dentures. The two fixed partial dentures change the clinical appearance of the
      patient.

PMID- 24673418
TI  - Acid demineralization susceptibility of dental enamel submitted to different
      bleaching techniques and fluoridation regimens.
AB  - The aim of the current study was to assess the acid demineralization
      susceptibility of bleached dental enamel submitted to different fluoride
      regimens. One hundred bovine enamel blocks (6*6*3 mm) were randomly divided into
      10 groups (n=10). Groups 1 and 2 received no bleaching. Groups 3 to 6 were
      submitted to an at-home bleaching technique using 6% hydrogen peroxide (HP; G3
      and G4) or 10% carbamide peroxide (CP; G5 and G6). Groups 7 to 10 were submitted
      to an in-office bleaching technique using 35% HP (G7 and G8) or 35% CP (G9 and
      G10). During bleaching, a daily fluoridation regimen of 0.05% sodium fluoride
      (NaF) solution was performed on groups 3, 5, 7, and 9, while weekly fluoridation
      with a 2% NaF gel was performed on groups 4, 6, 8, and 10. The samples in groups
      2 to 10 were pH cycled for 14 consecutive days. The samples from all groups were
      then assessed by cross-sectional Knoop microhardness at different depths from the
      outer enamel surface. The average Knoop hardness numbers (KHNs) were compared
      using one-way analysis of variance and Tukey tests (alpha=0.05). The comparison
      between groups 1 and 2 showed that the demineralization method was effective. The
      comparison among groups 2 to 6 showed the same susceptibility to acid
      demineralization, regardless of the fluoridation method used. However, the
      samples from groups 8 and 10 showed more susceptibility to acid demineralization
      when compared with group 2 (p<0.05). Groups 7 and 9 provided similar results to
      group 2, but the results of those groups were different when compared with groups
      8 and 10. The use of 6% HP and 10% CP associated with daily or weekly
      fluoridation regimens did not increase the susceptibility of enamel to acid
      demineralization. However, the use of 35% HP and 35% CP must be associated with a
      daily fluoridation regimen, otherwise the in-office bleaching makes the bleached
      enamel more susceptible to acid demineralization.

PMID- 24673419
TI  - Relation of myocardial systolic mechanics to serum ferritin level as a
      prognosticator in thalassemia patients undergoing repeated transfusion.
AB  - INTRODUCTION: Myocardial iron overload leading to congestive heart failure (HF)
      or arrhythmias is a recognized complication in thalassemia patients undergoing
      chronic blood transfusion. The relationship between myocardial iron load,
      subclinical systolic dysfunction, and clinical events remains less well known.
      MATERIALS AND METHODS: We studied a total of 77 subjects, comprising 37
      thalassemia patients (mean age: 24.2 +/- 5.5 years) with a history of repeated
      blood transfusions, in addition to 40 age- and gender-matched controls (mean age:
      24 +/- 4.5 years). Serum ferritin levels were checked in all subjects, as well as
      semiautomated quantification of left ventricular (LV) longitudinal,
      circumferential, and radial deformations assessed by two-dimensional (2D) speckle
      tracking analysis. RESULTS: Compared with the control group, thalassemia patients
      showed significantly larger LV mass index and lower myocardial deformations (P <
      0.05), but left ventricular ejection fraction (LVEF) did not differ significantly
      (P = 0.233). There was a significant linear correlation between serum ferritin
      level and longitudinal (r = 0.44, P = 0.0078) and radial strain (r = -0.46, P =
      0.0051), with optimal cutoff provided to be -15.48%, -21.31%, and 26.67% for
      longitudinal, circumferential, and radial strain in predicting clinical events,
      respectively. During a median of 802.5 days follow-up, 11 clinical composites (HF
      incidence, ventricular tachyarrhythmia, and death) occurred (N = 9 subjects);
      subjects with composites had significantly reduced longitudinal and radial strain
      compared to those without (both P < 0.05). After adjusting for age, sex, serum
      ferritin level, and LV mass index, a worsening of longitudinal strain remained as
      an independent predictor of clinical events and death (HR: 6.05, P = 0.033).
      CONCLUSION: Subclinical systolic dysfunction appears more likely in thalassemia
      subjects with a history of repeated blood transfusions, which further correlated
      with serum ferritin levels. In addition, worsening LV myocardial deformation
      parameters may play an independent role in predicting clinical outcomes beyond
      traditional measures in this population.

PMID- 24673421
TI  - A Fab fragment directed against the neural cell adhesion molecule L1 enhances
      functional recovery after injury of the adult mouse spinal cord.
AB  - Lack of permissive mechanisms and abundance of inhibitory molecules in the
      lesioned central nervous system of adult mammals contribute to the failure of
      functional recovery, which leads to severe disabilities in motor functions or
      pain. Previous studies have indicated that the neural cell adhesion molecule L1
      constitutes a viable target to promote regeneration. In the present study, we
      describe the cloning, functional expression in Escherichia coli cells and
      purification of a recombinant alphaL1 Fab fragment that binds to L1 with
      comparable activity as the function-triggering monoclonal antibody 557.B6 and
      induces neurite outgrowth and neuronal survival in cultured neurons, despite its
      monovalent function. Infusion of alphaL1 Fab into the lesioned spinal cord of
      mice enhanced functional recovery after thoracic spinal cord compression injury.
      alphaL1 Fab treatment resulted in reduced scar volume, enhanced number of
      tyrosine hydroxylase-positive axons and increased linear density of VGLUT1
      (vesicular glutamate transporter 1) on motoneurons. Furthermore, the number and
      soma size of ChAT (choline acetyltransferase)-positive motoneurons and the linear
      density of ChAT-positive boutons on motoneurons as well as parvalbumin-positive
      interneurons in the lumbar spinal cord were elevated. Stimulation of endogenous
      L1 by application of the alphaL1 Fab opens new avenues for recombinant antibody
      technology, offering prospects for therapeutic applications after traumatic
      nervous system lesions.

PMID- 24673420
TI  - PML-RARA fusion resulting from a cryptic insertion of RARA gene into PML gene
      without the reciprocal RARA-PML fusion: clinical, cytogenetic, and molecular
      characterization and prognosis.
AB  - We describe a case of acute promyelocytic leukemia in a 61-yr-old woman with a
      cryptic insertion of RARA gene into PML gene. Using a combination of cytogenetic
      and molecular methods, we confirmed the insertion and presence of the PML-RARA
      transcript and lack of the reciprocal RARA-PML transcript. Although such cryptic
      insertions leading to a PML-RARA fusion have been previously reported, we show
      that such variant insertions, based on our case, appear to have the same
      prognostic significance as the classical t(15;17)(q22;q21).

PMID- 24673422
TI  - Effects of heteroatoms on electronic states of divanadium-substituted gamma
      Keggin-type polyoxometalates.
AB  - Effects of heteroatoms on electronic states of divanadium-substituted gamma
      Keggin-type polyoxometalates (TBA)4[gamma-XV2W10O38(MU-OH)(MU-OR)] (X = Ge, Si; R
      = Me, Et, n-Pr, H; TBA = tetra(n-butyl)ammonium) and (TBA)4[gamma-XV2W10O38(MU
      O)] (X = Ge, Si) were investigated, using a combination of nuclear magnetic
      resonance spectroscopy and density functional theory (DFT) calculations. Both the
      substitution of SiO4 heteroatom units with larger GeO4 ones and the introduction
      of more electronegative alkoxo groups in place of hydroxo groups resulted in
      deshielding of the vanadium nuclei. DFT calculations using the Def2-SVP basis set
      at TPSSh level of theory could well-reproduce the anionic moieties of a series of
      divanadium-substituted gamma-Keggin-type polyoxometalates, and the estimated
      chemical shifts approximately reproduced the experimental ones with the
      individual gauge localized orbital method (SO-IGLO) taking the spin-orbit
      interaction into account. The magnetic shielding (sigma) consists of sigmad +
      sigmap + sigmaSD + sigmaFC, where sigmad, sigmap, sigmaSD, and sigmaFC are
      diamagnetic, paramagnetic, spin-dipolar, and Fermi contact terms, respectively.
      The sigmap changed much among (TBA)4[gamma-XV2W10O38(MU-OH)2], (TBA)4[gamma
      XV2W10O38(MU-OH)(MU-OR)], and (TBA)4[gamma-XV2W10O38(MU-O)], while sigmad,
      sigmaSD, and sigmaFC did not change much. Therefore, the sigmap largely
      contributed to the magnetic shielding. Moreover, sigmap consisted of the occupied
      occupied transitions (s-terms) and the occupied-virtual ones (u-terms), and the u
      terms were predominant for sigmap. The most contributing occupied localized
      orbital consisted of the dz(2) orbital of vanadium, the pz orbital of terminal
      oxygen related to the V?O bond, and the pz orbital of oxygen of the XO4 unit,
      whereas the two virtual localized orbitals consisted of the dyz orbital of
      vanadium and the py orbital of terminal oxygen. Analysis of the structural and
      electronic characteristics of a series of divanadium-substituted gamma-Keggin
      type POMs revealed a linear correlation between both (51)V{H} chemical shifts and
      the reciprocal values of the energy gaps between the corresponding XO4
      predominant orbital HOMOs-X and the LUMOs+X (X = 0, 1, or 2). All these results
      indicate that neighboring XO4 units weakly interact with the addenda atoms and
      control the electronic states of polyoxometalates and the magnetic shielding of
      their addenda atoms. 

PMID- 24673423
TI  - Individual and sex-specific differences in intrinsic growth rate covary with
      consistent individual differences in behaviour.
AB  - The evolutionary causes of consistent individual differences in behaviour are
      currently a source of debate. A recent hypothesis suggests that consistent
      individual differences in life-history productivity (growth and/or fecundity) may
      covary with behavioural traits that contribute to growth-mortality trade-offs,
      such as risk-proneness (boldness) and foraging activity (voraciousness). It
      remains unclear, however, to what extent individual behavioural and life-history
      profiles are set early in life, or are a more flexible result of specific
      environmental or developmental contexts that allow bold and active individuals to
      acquire more resources. Longitudinal studies of individually housed animals under
      controlled conditions can shed light on this question. Since growth and behaviour
      can both vary within individuals (they are labile), studying between-individual
      correlations in behaviour and growth rate requires repeated scoring for both
      variables over an extended period of time. However, such a study has not yet been
      done. Here, we repeatedly measured individual mass seven times each, boldness 40
      times each and voracity eight times each during the first 4 months of life on 90
      individually housed crayfish (Cherax destructor). Animals were fed ad libitum,
      generating a context where individuals can express their intrinsic growth rate
      (i.e. growth capacity), but in which bold and voracious behaviour is not
      necessary for high resource acquisition (crayfish can and do hoard food back to
      their burrow). We show that individuals that were consistently bold over time
      during the day were also bolder at night, were more voracious and maintained
      higher growth rates over time than shy individuals. Independent of individual
      differences, we also observed that males were faster-growing, bolder and more
      voracious than females. Our findings imply that associations between bold
      behaviour and fast growth can occur in unlimited food contexts where there is no
      necessary link between bold behaviour and resource acquisition - offering support
      for the 'personality-productivity' hypothesis. We suggest future research should
      study links between consistent individual differences in behaviour and life
      history under a wider range of contexts, in order to shed light on the role of
      biotic and abiotic conditions in the strength, direction and stability of their
      covariance. 

PMID- 24673424
TI  - Designing conical intersections for light-driven single molecule rotary motors:
      from precessional to axial motion.
AB  - In the past, the design of light-driven single molecule rotary motors has been
      mainly guided by the modification of their ground-state conformational
      properties. Further progress in this field is thus likely to be achieved through
      a detailed understanding of light-induced dynamics of the system and the ways of
      modulating it by introducing chemical modifications. In the present theoretical
      work, the analysis of model organic chromophores and synthesized rotary motors is
      used for rationalizing the effect of electron-withdrawing heteroatoms (such as a
      cationic nitrogen) on the topography and branching plane of mechanistically
      relevant conical intersections. Such an analysis reveals how the character of
      rotary motion could be changed from a precessional motion to an axial rotational
      motion. These concepts are then used to design and build quantum chemical models
      of three distinct types of Schiff base rotary motors. One of these models,
      featuring the synthetically viable indanylidenepyrroline framework, has conical
      intersection structures consistent with an axial rotation not hindered by ground
      state conformational barriers. It is expected that this type of motor should be
      capable of funneling the photon energy into specific rotary modes, thus achieving
      photoisomerization quantum efficiencies comparable to those seen in visual
      pigments. 

PMID- 24673425
TI  - Elongation, alignment, and guided electrophoretic migration of ds-DNA in flow
      aligned hexagonal F127 gels.
AB  - Elongation, alignment, and electrophoretic migration of double stranded DNA (ds
      DNA) are investigated within flow aligned hexagonal Pluronic F127 mesophases
      contained in microfluidic channels. The DNA molecules are stained with YOYO-1 for
      visualization of their positions, conformations, and motions, which are recorded
      by wide-field fluorescence video microscopy. The videos show that the ds-DNA
      molecules are elongated in flow aligned hexagonal F127 mesophases, with the long
      axis of the DNA molecules aligned parallel to the flow direction. Elongation and
      alignment are most prevalent near the channel surface in the hexagonal mesophase.
      In contrast, little or no alignment is observed for the cubic mesophase. DNA
      elongation and alignment may involve adsorption of one strand end to the glass
      surface, or its capture by an adsorbed, structured surface layer of F127.
      Subsequent stretching of the DNA would then occur within the steep flow profile
      that exists near the glass surface during filling of the microfluidic channels.
      Videos recorded under the influence of applied electric fields demonstrate that
      the electrophoretic motions of the elongated, aligned DNA are strongly guided by
      the hexagonal mesophase structure. Electrophoretic migration is observed to occur
      exclusively along the local flow alignment direction within hexagonal mesophases
      for fields applied at 0, 45 and 90 degrees  to the flow alignment direction.
      These results show that ds-DNA interacts strongly with the micelles comprising
      the gel. These observations will lead to a better understanding of macromolecular
      interactions with nanostructured gels like those now being investigated for use
      in drug delivery and chemical separations. 

PMID- 24673426
TI  - A rapid thin-layer chromatography bioautographic method for detecting the
      monoamine oxidase inhibitors in plants.
AB  - It is well known that the isolation of monoamine oxidase (MAO) inhibitors from
      natural sources is an important strategy for drug development in the treatment of
      depression, Parkinson's disease and Alzheimer's disease. The present work
      describes developing a thin-layer chromatography (TLC) bioautographic method for
      detecting MAO inhibitors from plant extracts. The basic principle of the method
      is that the enzyme oxidises tryptamine into an aldehyde which in turn reacts with
      3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide to form a blue
      formazan which makes a blue-coloured background on the TLC plates. Inhibitors of
      MAO produced white spots on the background. The new TLC bioautographic method has
      several advantages such as lower consumption of the enzyme, shorter experimental
      time, more easily observed background of TLC plate and better reproducibility.
      The detection limits were 10 ng for several known MAO inhibitors.

PMID- 24673427
TI  - Influence of smoking on disease severity and antimalarial therapy in cutaneous
      lupus erythematosus: analysis of 1002 patients from the EUSCLE database.
AB  - BACKGROUND: In recent years it has been controversially discussed in the
      literature if smoking is associated with the activity of cutaneous lupus
      erythematosus (CLE) and the efficacy of antimalarial agents. OBJECTIVES: To
      investigate the influence of smoking on disease severity and antimalarial
      treatment in patients with CLE using the Core Set Questionnaire of the European
      Society of Cutaneous Lupus Erythematosus (EUSCLE). METHODS: A total of 1002
      patients (768 female, 234 male) with different CLE subtypes were included in this
      cross-sectional study, which was performed in 14 different countries. Smoking
      behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and
      statistically analysed using an SPSS database. The results were correlated with
      the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the
      efficacy of antimalarial treatment. RESULTS: A high percentage (87.2%) of the 499
      patients with CLE, who have ever smoked, had already smoked at the date of their
      first diagnosis. Patients with intermittent CLE have ever smoked significantly
      more often than patients with subacute CLE (P < 0.05) and chronic CLE (P < 0.05).
      The total CLASI activity and damage score of patients with CLE was 6.6 +/- 7.1
      and 2.6 +/- 4.3, respectively, and was higher in patients who have ever smoked
      than in nonsmokers. Antimalarial treatment was successful in 84.3% of cases, with
      a significantly higher efficacy in nonsmokers than in patients with CLE who have
      ever smoked (P < 0.05). CONCLUSIONS: This analysis of a multicentre study
      population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire
      confirms that smoking negatively influences CLE disease severity and the efficacy
      of antimalarial treatment.

PMID- 24673428
TI  - Optimization of pH values to formulate the bireagent kit for serum uric acid
      assay.
AB  - A new formulation of the bireagent kit for serum uric acid assay was developed
      based on the effects of pH on enzyme stability. At 4  degrees C, half-lives of
      uricases from Bacillus fastidious and Arthrobacter globiforms were longer than 15
      months at pH 9.2, but became shorter at pH below 8.0; half-lives of ascorbate
      oxidase and peroxidase were comparable at pH 6.5 and 7.0, but became much shorter
      at pH higher than 7.4. In the new formulation of the bireagent kit, Reagent A
      contained peroxidase, 4-aminoantipyrine, and ascorbate oxidase in 50 mM phosphate
      buffer at pH 6.5; Reagent B contained B. fastidious or A. globiforms uricase in
      50 mM sodium borate buffer at pH 9.2; Reagents A and B were mixed at 4:1 to
      produce a final pH from 7.2 to 7.6 for developing a stable color. The new
      bireagent kit consumed smaller quantities of three enzymes for the same shelf
      life. With the new bireagent kit, there were linear responses of absorbance at
      546 nm to uric acid up to 34 mM in reaction mixtures and a good correlation of
      uric acid levels in clinical sera with those by a commercial kit, but stronger
      resistance to ascorbate. Therefore, the new formulation was advantageous. 

PMID- 24673429
TI  - Ductal epithelial expression of Ro52 correlates with inflammation in salivary
      glands of patients with primary Sjogren's syndrome.
AB  - Ro52 is an E3 ubiquitin ligase with a prominent regulatory role in inflammation.
      The protein is a common target of circulating autoantibodies in rheumatic
      autoimmune diseases, particularly Sjogren's syndrome (SS). In this study we aimed
      to investigate the expression of the SS target autoantigen Ro52 in salivary
      glands of patients with primary Sjogren's syndrome (pSS). Ro52 expression was
      assessed by immunohistochemical staining of paraffin-embedded and frozen salivary
      gland biopsies from 28 pSS patients and 19 non-pSS controls from Swedish and
      Norwegian registries, using anti-human Ro52 monoclonal antibodies. The degree and
      pattern of staining and inflammation was then evaluated. Furthermore, secreted
      Ro52 protein was measured in saliva and serum samples from the same individuals
      through a catch-enzyme-linked immunosorbent assay (ELISA). Ro52 was highly
      expressed in all the focal infiltrates in pSS patients. Interestingly, a
      significantly higher degree of Ro52 expression in ductal epithelium was observed
      in the patients compared to the non-pSS controls (P < 0.03). Moreover, the degree
      of ductal epithelial expression of Ro52 correlated with the level of inflammation
      (Spearman's r = 0.48, P < 0.0120). However, no secreted Ro52 protein could be
      detected in serum and saliva samples of these subjects. Ro52 expression in ductal
      epithelium coincides with degree of inflammation and is up-regulated in pSS
      patients. High expression of Ro52 might result in the breakage of tolerance and
      generation of Ro52 autoantibodies in genetically susceptible individuals. We
      conclude that the up-regulation of Ro52 in ductal epithelium might be a
      triggering factor for disease progression in SS. 

PMID- 24673431
TI  - Bioactive nanoparticle through postmodification of colloidal silica.
AB  - Bioactive nanoparticles with controllable size and good colloidal stability were
      synthesized through surface modification of colloidal silica nanoparticles with
      Ca(OH)2 as the modifier. These modified nanoparticles showed good bioactivity,
      showing evidence of hydroxyapatite formation when incubated in simulated body
      fluid within 3 days. Comparison of bioactivity was made among different sized
      particles from nanoscale to microscale. It was found the bioactivity of these
      calcium modified colloidal silica particles generally decreased with particle
      size in the explored size range (40 nm particles showed bioactivity within 1
      day). These particles were also found to be noncytotoxic but promote
      preosteoblast growth, thus making them promising bioactive additives for bone
      repair materials. 

PMID- 24673430
TI  - Semaphorin 3A alters endothelial cell immunogenicity by regulating Class II
      transactivator activity circuits.
AB  - BACKGROUND: Endothelial cells (ECs) play a pivotal role in the allogeneic immune
      response upon transplantation. Semaphorin 3A (Sema3A) was implicated in the
      modulation of EC growth, but its effects on immunogenicity were not previously
      investigated. STUDY DESIGN AND METHODS: ECs were transduced with a lentiviral
      vector encoding for the green fluorescence protein (GFP) sequence under the
      control of a Class II transactivator (CIITA)-dependent promoter. Upon stimulation
      of nonmodified ECs with recombinant Sema3A protein, mRNA and protein levels of
      CIITA, HLA-DR, and Sema3A receptors were evaluated. An enzyme-linked
      immunosorbent assay was developed to quantify Sema3A levels in the sera of kidney
      transplanted patients. RESULTS: Sema3A stimulation of lentiviral vector encoding
      for the GFP sequence ECs caused a significant up regulation of the transgene
      expression, indicating an increase in CIITA levels. Stimulation of nonmodified
      ECs with Sema3A resulted in an up regulation of CIITA expression, which was
      associated with enhanced HLA-DR levels and an increase in alloreactive CD4+ T
      cell proliferation. Sema3A receptor expression was enhanced by CIITA,
      establishing a positive feedback loop. Higher levels of Sema3A were observed in
      sera of patients presenting with organ rejection. CONCLUSION: This study links
      Sema3A signaling in ECs with increased CIITA levels and higher HLA-DR expression,
      resulting in CD4+ T-cell activation, which might have important implications for
      tissue and organ transplantation.

PMID- 24673432
TI  - Treatment options for managing atherogenic dyslipidemia and fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease in Western countries with up to 30% of the population affected.
      Since NAFLD is associated with an increased risk of cardiovascular (CV) disease,
      these patients should be stratified for CV risk factors, including atherogenic
      dyslipidemia, and managed accordingly. Lifestyle modifications represent an
      effective treatment for NAFLD, since most patients are overweight or obese. Also,
      promising, but not conclusive, results are available for current pharmacologic
      treatment. Drugs potentially effective against NAFLD include insulin sensitisers
      as well as fibrates and omega-3 polyunsaturated fatty acids, while there is
      reluctance to use statins in patients with suspected or established chronic liver
      disease. Several other therapeutic options are potentially available, and more
      data are expected from new peroxisome proliferator-activated receptor agonists
      and incretin-based therapies. 

PMID- 24673434
TI  - Effect of temperature on the visualization by digital color mapping of latent
      fingerprint deposits on metal.
AB  - Visualization of fingerprint deposits by digital color mapping of light reflected
      from the surface of heated brass, copper, aluminum, and tin has been investigated
      using Adobe(r) Photoshop(r). Metals were heated to a range of temperatures (T)
      between 50 degrees C and 500 degrees C in 50 degrees C intervals with enhancement
      being optimal when the metals are heated to 250 degrees C, 350 degrees C, 50
      degrees C, and 300 degrees C, respectively, and the hue values adjusted to 247
      degrees , 245 degrees , 5 degrees , and 34 degrees , respectively. Fingerprint
      visualization after color mapping was not degraded by subsequent washing of the
      metals and color mapping did not compromise the visibility of the fingerprint for
      all values of T. The optimum value of T for fingerprint visibility is
      significantly dependent of the standard reduction potential of the metal with
      Kendall's Tau (tau) = 0.953 (p < 0.001). For brass, this correlation is obtained
      when considering the standard reduction potential of zinc rather than copper.

PMID- 24673433
TI  - Transient nephrogenic diabetes insipidus caused by fetal exposure to haloperidol.
AB  - Haloperidol is commonly used in the treatment of psychiatric disorders. Data from
      animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in
      high doses. For the first time, we report a neonate with transient nephrogenic
      diabetes insipidus (DI) caused by fetal exposure to haloperidol. The magnitude of
      risk associated with the use of haloperidol during pregnancy appears to be small,
      but nephrogenic DI secondary to haloperidol is a serious condition with the risk
      of hypernatremic dehydration. Haloperidol can have adverse effects on the fetus
      and newborn infant, that's why one should prevent the use of haloperidol during
      pregnancy and lactation.

PMID- 24673435
TI  - Characterization of skin sensitizers from autoxidized citronellol - impact of the
      terpene structure on the autoxidation process.
AB  - BACKGROUND: Citronellol is a frequently used fragrance compound in consumer
      products. It is present in fragrance mix II, which is used for screening of
      contact allergy to fragrances. Because of its chemical structure, citronellol
      could be susceptible to autoxidation. OBJECTIVES: To compare the behaviour of
      citronellol with that of the structurally similar compounds linalool and
      geraniol, in terms of ability to autoxidize, the products formed, and the
      sensitization potencies of these. METHODS: Citronellol was exposed to air, and
      autoxidation was followed by gas chromatography-mass spectrometry (GC-MS)
      analysis after derivatization of thermolabile compounds. The sensitizing
      potencies of the oxidation mixture and its major oxidation compounds were
      examined with the local lymph node assay. RESULTS: The concentration of
      citronellol decreased while the sensitization potency increased in air-exposed
      samples over time, with hydroperoxides being identified as the major oxidation
      products and main skin sensitizers. CONCLUSIONS: The present study shows the
      impact of the absence of the 2,3-double bond in the citronellol structure on the
      oxidation pathways for formation of oxidation products. The study also shows the
      usefulness of our new GC-MS method for quantification of the citronellol
      oxidation products, especially the hydroperoxides. The investigated citronellol
      hydroperoxides could be important allergens, owing to the high concentrations
      detected and frequent exposure to citronellol in the population.

PMID- 24673436
TI  - Type 1 collagen as a potential niche component for CD133-positive glioblastoma
      cells.
AB  - Cancer stem cells are thought to be closely related to tumor progression and
      recurrence, making them attractive therapeutic targets. Stem cells of various
      tissues exist within niches maintaining their stemness. Glioblastoma stem cells
      (GSCs) are located at tumor capillaries and the perivascular niche, which are
      considered to have an important role in maintaining GSCs. There were some
      extracellular matrices (ECM) on the perivascular connective tissue, including
      type 1 collagen. We here evaluated whether type 1 collagen has a potential niche
      for GSCs. Imunohistochemical staining of type 1 collagen and CD133, one of the
      GSCs markers, on glioblastoma (GBM) tissues showed CD133-positive cells were
      located in immediate proximity to type 1 collagen around tumor vessels. We
      cultured human GBM cell lines, U87MG and GBM cells obtained from fresh surgical
      tissues, T472 and T555, with serum-containing medium (SCM) or serum-free medium
      with some growth factors (SFM) and in non-coated (Non-coat) or type 1 collagen
      coated plates (Col). The RNA expression levels of CD133 and Nestin as stem cell
      markers in each condition were examined. The Col condition not only with SFM but
      SCM made GBM cells more enhanced in RNA expression of CD133, compared to Non
      coat/SCM. Semi-quantitative measurement of CD133-positive cells by
      immunocytochemistry showed a statistically significant increase of CD133-positive
      cells in Col/SFM. In addition, T472 cell line cultured in the Col/SFM had
      capabilities of sphere formation and tumorigenesis. Type 1 collagen was found in
      the perivascular area and showed a possibility to maintain GSCs. These findings
      suggest that type 1 collagen could be one important niche component for CD133
      positive GSCs and maintain GSCs in adherent culture.

PMID- 24673437
TI  - Scolopendra bites: a report of two cases and review of the literature.
AB  - BACKGROUND: Centipedes are arthropods belonging to the class Chilopoda.
      Approximately 3000 species have been described. Centipedes are found more
      commonly in tropical and subtropical countries. Centipedes possess venomous
      fangs. The Scolopendra represent the best-known genus of centipede. METHODS: We
      describe two cases of severe skin reactions caused by Scolopendra subspinipes
      bites. RESULTS: Both patients were bitten on the hand. The clinical picture was
      characterized by severe erythematous edema. In addition, one patient presented
      with a blister. Both patients complained of severe pain. Laboratory examinations
      showed leukocytosis and an increase in erythrocyte sedimentation rate (ESR).
      Complete remission was achieved within two weeks by means of paracetamol and oral
      prednisone. CONCLUSIONS: Western dermatologists should be aware of the
      possibility of severe skin reactions caused by centipede bites.

PMID- 24673438
TI  - Transient CNS deficits and migrainous auras in individuals without a history of
      headache.
AB  - OBJECTIVE: To demonstrate that benign transient focal neurological symptoms
      represent equivalents of migraine auras without headache. BACKGROUND: Benign
      focal neurological symptoms suggesting cerebral dysfunction are common and
      usually prompt an extensive diagnostic workup, but their etiology is often not
      elucidated. We hypothesized that benign transient focal neurological symptoms
      represent equivalents of migraine auras without headache, even in subjects who
      have never experienced migraine headaches. METHODS: We led a cross-sectional
      study and identified individuals who presented at least 1 episode of unexplained
      transient focal neurological symptoms suggestive of cerebral dysfunction, but no
      history of migraine headache, among physicians and inpatients of an academic
      hospital. Cortical hyperexcitability, assessed by occipital transcranial magnetic
      stimulation (oTMS), was used as a marker of possible migraine auras without
      headache. RESULTS: Frequency of transient focal neurological symptoms suggestive
      of cerebral dysfunction among the physicians who responded was 9% (21/233), vs
      0.09% (6/690) of inpatients. Most episodes resembled typical visual migrainous
      auras. Motor, sensory, and language dysfunction were more common among inpatients
      than among physicians. oTMS induced phosphenes in 12/16 (75%) subjects and in
      none of 10 controls. CONCLUSION: Benign focal neurological symptoms were common
      in our population and likely represent migraine aura without headache. Non-visual
      symptoms are less common and lead to medical consultation. oTMS is abnormal in
      most cases, supporting the diagnosis of migraine aura without headache and
      helping separate this benign condition from transient ischemic attacks.

PMID- 24673439
TI  - Organocatalytic approach for C(sp3)-H bond arylation, alkylation, and amidation
      of isochromans under facile conditions.
AB  - A new catalytic approach for the synthesis of isochroman derivatives via direct
      C(sp(3))-H bond arylation is described. The oxidation reaction with
      [bis(trifluoroacetoxy)iodo]benzene facilitates the regeneration of 2,3-dichloro
      5,6-dicyano-1,4-benzoquinone in the C(sp(3))-H bond arylation of isochroman. The
      reaction conditions can also be used for alkyl Grignard reagents and amides to
      afford the corresponding isochroman derivatives. 

PMID- 24673441
TI  - Development and verification of air balance gas primary standards for the
      measurement of nitrous oxide at atmospheric levels.
AB  - The Gas Metrology Group at the National Institute of Standards and Technology
      (NIST) became active in developing primary standards at ambient levels of N2O in
      the 1980s, and this has continued through to the present. In recent years,
      interest in NIST-traceable standards has increased-not only at the ambient level
      of approximately 325 nmol mol(-1) (ppb) but at micromole per mole (ppm) levels as
      well. In order to support two in-process dry whole air standard reference
      materials (SRMs 1720 and 1721) and the NIST Traceable Reference Materials (NTRM)
      program, a project was implemented in the Gas Metrology Group to produce a
      complete suite of new primary standard materials (PSMs) of N2O with synthetic air
      (O2/N2) as the balance gas. Six levels of dilution, approximately 1 order of
      magnitude apart, were gravimetrically prepared and verified. Each level serves as
      the "parent mix" for the next level. This discussion describes the process of
      producing each level and then verifying its amount-of-substance fraction.
      Expanded uncertainties, k = 2, of 0.025% relative to the gravimetric amount-of
      substance fraction were obtained at the ambient level. One standard from the
      final group of standards at the ambient amount-of-substance fraction level was
      compared with standards from the National Oceanographic and Atmospheric
      Administration and the Scripps Institution of Oceanography, two organizations
      experienced in gas standards preparation and ambient whole air measurements, and
      shows agreement to 0.07 nmol mol(-1) (0.02% relative) and 0.20 nmol mol(-1)
      (0.06% relative), respectively. 

PMID- 24673440
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes astrocyte activation and the
      secretion of tumor necrosis factor-alpha via PKC/SSeCKS-dependent mechanisms.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental
      pollutant that could induce significant toxic effects in the human nervous
      system. However, the underlying molecular mechanism has not been entirely
      elucidated. Reactive astrogliosis has implicated in various neurological diseases
      via the production of a variety of pro-inflammatory mediators. Herein, we
      investigated the potential role of TCDD in facilitating astrocyte activation and
      the underlying molecular mechanisms. We showed that TCDD induced rapid astrocyte
      activation following TCDD exposure, which was accompanied by significantly
      elevated expression of Src-Suppressed-C Kinase Substrate (SSeCKS), a protein
      involved in protein kinase C (PKC)-mediated Nuclear Factor kappa B signaling,
      suggesting a possible involvement of PKC-induced SSeCKS activation in TCDD
      triggered reactive astroglia. In keeping with the finding, we found that the
      level of phosphorylated Nuclear Factor kappa B p65 was remarkably increased after
      TCDD treatment. Furthermore, interference of SSeCKS attenuated TCDD-induced
      inducible nitric oxide synthase, glial fibrillary acidic protein, phospho-p65
      expression, and tumor necrosis factor-alpha secretion in astrocytes. In addition,
      pre-treatment with PKC inhibitor also attenuated TCDD-induced astrocyte
      activation, as well as SSeCKS expression. Interestingly, we found that TCDD
      treatment could lead to SSeCKS perinuclear localization, which could be abolished
      after treatment with PKC inhibitor. Finally, we showed that inhibition of PKC
      activity or SSeCKS expression would impair TCDD-triggered tumor necrosis factor
      alpha secretion. Our results suggested that TCDD exposure could lead to astrocyte
      activation through PKC/SSeCKS-dependent mechanisms, highlighting that astrocytes
      might be important target of TCDD-induced neurotoxicity. 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) elicits neurotoxic effects. Here, we show TCDD
      induces pro-inflammatory responses in astrocytes. TCDD initiates an increase of
      [Ca2+]i, followed by the activation of PKC, which then induces the activation of
      Src-suppressed C-kinase substrate (SSeCKS). SSeCKS promotes NF-kappaB activation
      and the secretion of TNF-alpha and nitric oxide in astrocytes. 

PMID- 24673442
TI  - Tenosynovitis with rice body formation presenting as a cutaneous abscess.
AB  - A 62-year-old woman with a past medical history of rheumatoid arthritis was
      referred to the Department of Dermatology because of an enlarging cutaneous
      lesion on the right thumb which resembled a soft tissue infection. She had
      received antibiotics without significant improvement. Clinical examination
      revealed an erythematous nodule involving almost the whole surface of the distal
      phalanx with spontaneous drainage of countless of small yellowish ovoid granules.
      Histopathologic study of these structures showed an inner core of amorphous
      acidophilic material with some interspersed chronic inflammatory cells and a
      surrounding thin fibrin layer. Special stains and cultures were negative for
      parasites, bacterium and mycobacterium. Magnetic resonance imaging (MRI) revealed
      distension of the first and fifth finger flexor sheaths and common finger flexor
      sheath. These areas were filled by fluid and multiple small nodular lesions. A
      diagnosis of non-infectious rice body tenosynovitis was rendered and surgical
      removal was performed. Total recovery was observed with no evidence of recurrence
      after 6 months of follow-up. To our knowledge, this is the first report of rice
      body tenosynovitis presenting as a pseudoinflammatory cutaneous lesion with
      evolution to a cutaneous fistula with drainage of rice grain-like structures. The
      description of this impressive and peculiar clinical and histopathologic picture
      is important to further recognize similar cases.

PMID- 24673443
TI  - Application of the microarray technology to the transcriptional analysis of
      muscle phenotypes in pigs.
AB  - The transcriptome refers to the collection of all transcripts present in a cell.
      Gene expression has a very dynamic nature; it acts as a bridge between epigenetic
      marks, DNA sequence and proteins and changes to accommodate the requirements of
      the cell at each given time. Recent technological advances have created new
      opportunities to study complex phenotypes from a global point of view. From an
      animal production perspective, muscle transcriptomics has been investigated in
      relation to muscle growth, carcass fattening and meat quality traits. In this
      review, we discuss the impact of nutritional, anatomical and genetic factors on
      muscle gene expression and meat quality of pigs assessed by microarray
      technologies. Altogether, several common themes have been revealed by the in
      depth analysis of the current body of knowledge, for instance, the involvement of
      genes related to energy balance and substrate turnover in the
      oxidative/glycolytic phenotype of red/white muscle fibre types and in the storage
      of intramuscular fat. The review also covers recent advances in the discovery of
      expression QTL and regulatory RNAs in porcine breeds as well as technical
      developments in the field of deep-sequencing technologies that are expected to
      substantially increase our knowledge about the genetic architecture of meat
      quality and production traits. 

PMID- 24673444
TI  - Skeletal muscle apolipoprotein B expression reduces muscular triglyceride
      accumulation.
AB  - BACKGROUND: Lipid accumulation in skeletal muscle is associated with impaired
      insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein
      secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride
      transfer protein (MTP) affects lipid homeostasis. DESIGN: In this study, we
      investigated whether expression of a human apoB transgene affects triglyceride
      accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice.
      RESULTS: Expression of apoB and MTP mRNA and the human apoB transgene was seen in
      skeletal muscle of the transgene mice. Human apoB transgenic mice accumulated 28%
      less triglycerides in skeletal myocytes after one year of fat-feeding as compared
      with WT mice (32 +/- 5, n = 10 vs. 44 +/- 4 nmol/mg ww, n = 13, p = 0.04).
      Moreover, expression of human apoB in fat-fed mice was associated with 32% (p =
      0.02) and 37% (p = 0.01) lower plasma insulin levels after 9 and 12 months,
      respectively, improved intra peritoneal glucose tolerance after 6 months, and a
      trend towards increased insulin-stimulated glucose uptake in isolated skeletal
      muscle. CONCLUSIONS: The data suggests that overexpression of apoB decreases
      skeletal muscle lipid accumulation and attenuates peripheral insulin resistance
      in obese mice.

PMID- 24673445
TI  - Baseline evaluation in youth ice hockey players: comparing methods for
      documenting prior concussions and attention or learning disorders.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: To examine differences in concussion
      history and attention or learning disorders reported by elite youth ice hockey
      players, using a questionnaire that allows parental input compared to a clinic
      based test battery that does not. BACKGROUND: A history of previous concussion
      and the presence of attention or learning disorders can affect concussion
      management decisions; however, youth athletes may not accurately report their
      medical history because they may not know or recall important details. METHODS:
      The sample included 714 Bantam (ages 12-14 years) and Midget (ages 15-17 years)
      ice hockey players (601 male, 113 female) from the most elite divisions of play
      (AA and AAA). Players completed a take-home preseason questionnaire (PSQ) with
      the input of a parent/guardian, and also independently completed the baseline
      Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) at the
      beginning of the 2011-2012 hockey season. RESULTS: In 21.1% (95% confidence
      interval: 18.1%, 24.1%) of cases, there was disagreement between the PSQ and
      ImPACT in the number of previous concussions reported. Among those who reported
      an attention disorder on the PSQ, 85.7% also reported an attention disorder on
      the ImPACT. Only 9.5% of those who reported a learning disorder on the PSQ also
      reported a learning disorder on the ImPACT. CONCLUSION: In 1 of 5 players,
      reported concussion history differed between the PSQ and ImPACT, and there was
      substantial disagreement between instruments for those reporting learning
      disorders. The method of obtaining medical history may, therefore, affect
      baseline and postconcussion evaluations.

PMID- 24673446
TI  - Patellofemoral joint stress during weight-bearing and non-weight-bearing
      quadriceps exercises.
AB  - STUDY DESIGN: Single-group, repeated-measures design. OBJECTIVE: To compare
      patellofemoral joint (PFJ) stress among weight-bearing and non-weight-bearing
      quadriceps exercises. BACKGROUND: An important consideration when prescribing
      exercises to strengthen the quadriceps in persons with patellofemoral pain is to
      minimize PFJ loading. Currently, there is disagreement in the literature as to
      which exercises and ranges of motion best accomplish this goal. METHODS: Ten
      healthy subjects participated. Lower extremity kinematics, kinetics, and
      electromyography of the knee musculature were obtained during a weight-bearing
      squatting exercise and 2 non-weight-bearing knee extension exercises: (1) knee
      extension with variable resistance, and (2) knee extension with constant
      resistance. A previously described biomechanical model was used to estimate PFJ
      stress at 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75
      degrees , and 90 degrees  of knee flexion. PFJ stress was compared among the 3
      exercises using a 2-way analysis of variance with repeated measures. RESULTS:
      Compared to the 2 non-weight-bearing exercises, the squat exercise produced
      significantly higher PFJ stress at 90 degrees , 75 degrees , and 60 degrees  of
      knee flexion. Conversely, the 2 non-weight-bearing exercises produced
      significantly higher PFJ stress at 30 degrees , 15 degrees , and 0 degrees  of
      knee flexion when compared to the squat exercise. The knee-extension-with
      variable-resistance exercise produced significantly lower PFJ stress than the
      knee-extension-with-constant-resistance exercise at 90 degrees , 75 degrees , and
      60 degrees  of knee flexion. CONCLUSION: To minimize PFJ stress while performing
      quadriceps exercises, our data suggest that the squat exercise should be
      performed from 45 degrees  to 0 degrees  of knee flexion and the knee-extension
      with-variable-resistance exercise should be performed from 90 degrees  to 45
      degrees  of knee flexion.

PMID- 24673447
TI  - The Danish version of the modified Constant-Murley shoulder score: reliability,
      agreement, and construct validity.
AB  - STUDY DESIGN: Test-retest study. Objectives To assess the reliability, agreement,
      and validity of the Danish version of the modified Constant-Murley score (CMS).
      BACKGROUND: Modified CMS guidelines were published in 2008. These modifications
      have recently been translated and cross-culturally adapted into a Danish version.
      However, the reliability and the validity of this version have yet to be
      established. METHODS: A total of 45 patients with shoulder impingement syndrome
      were examined by 2 raters using the modified version of the CMS and a
      questionnaire that included the Oxford shoulder score. Both raters had a minimum
      of experience using the CMS. Intrarater and interrater agreement and reliability
      were examined and compared. Construct validity was assessed by the correlation
      between the scores of the CMS and the Oxford shoulder score. RESULTS: The minimal
      detectable change was estimated to be 13 and 11 points for raters A and B,
      respectively. The intraclass correlation coefficient was 0.93 for rater A and
      0.95 for rater B. Interrater comparison demonstrated a minimal detectable change
      of 12 points and an intraclass correlation coefficient of 0.94. The correlation
      coefficient between the CMS and the Oxford shoulder score was 0.76. CONCLUSION:
      The intrarater and interrater reliability and agreement of the Danish version of
      the modified CMS were found to be acceptable, and construct validity was
      confirmed.

PMID- 24673448
TI  - Reliability and minimal detectable change of 3-dimensional scapular orientation
      in individuals with and without shoulder impingement.
AB  - STUDY DESIGN: Clinical measurement. OBJECTIVE: To establish trial-to-trial within
      day and between-day reliability, standard error of measurement, and minimal
      detectable change of scapular orientation during elevation and lowering of the
      arm, and with the arm relaxed at the side, in individuals with and without
      shoulder impingement. BACKGROUND: Electromagnetic devices are commonly used to
      measure 3-D scapular kinematics during arm elevation in different conditions and
      for intervention studies. However, there is a lack of studies that evaluate
      within- and between-day reliability of these measurements. METHODS: The subjects
      were allocated to either a control group or an impingement group. Kinematic data
      were collected using the Flock of Birds electromagnetic device during elevation
      and lowering of the arm in the sagittal plane on 2 different occasions, separated
      by 3 to 5 days. Forty-nine subjects were tested for within-day reliability. Forty
      three subjects were reassessed for between-day reliability. RESULTS: Intraclass
      correlation coefficients for within- and between-day assessment of scapular
      orientation during elevation and lowering of the arm in both groups ranged from
      0.92 to 0.99 and from 0.54 to 0.88, respectively. Intraclass correlation
      coefficients for assessment of scapular orientation with the arms relaxed at the
      side in both groups ranged from 0.66 to 0.95. The standard error of measurement
      for between-day measurements ranged from 3.37 degrees  to 7.44 degrees  for both
      groups. The minimal detectable change for between-day measurements increased from
      7.81 degrees  at the lower to 17.27 degrees  at the higher humerothoracic
      elevation angles. CONCLUSION: These results support the use of Flock of Birds to
      measure scapular orientations in subjects with and without impingement symptoms.
      The measurements showed excellent within-day reliability but were not highly
      reliable over time.

PMID- 24673450
TI  - Concerted functions of anions and cations in a molecular ionic crystal with
      stable three-dimensional micropores.
AB  - The molecular ionic crystal [Cr3O(OOCCH?CH2)6(H2O)3]3[alpha-PW12O40].15H2O [Ia]
      with stable three-dimensional micropores and a minimum aperture of 3.3 A was
      synthesized with a phosphododecatungstate [alpha-PW12O40](3-) (polyoxometalate,
      POM) and a macrocation with acrylate ligands [Cr3O(OOCCH?CH2)6(H2O)3](+). The
      porous structure of Ia was basically constructed by an arrangement of
      macrocations forming a six-membered ring: vinyl groups (CH?CH2) of adjacent
      macrocations were aligned parallel to each other, suggesting a weak dispersion
      force between them. A guest-free phase [Cr3O(OOCCH?CH2)6(H2O)3]3[alpha-PW12O40]
      [Ib] was formed by the treatment of Ia in vacuo at room temperature without any
      structure change. Compound Ib showed shape-selective sorption of CO2 and C2H2
      (molecular size = 3.3 A) over N2 (3.6 A) and methane (3.7 A), and the sorption
      enthalpy of C2H2 was larger than that of CO2. The high affinity toward C2H2 was
      further confirmed as follows: the Monte Carlo simulations of the optimized
      geometries of C2H2 in Ib showed that both hydrogen atoms were in the vicinity of
      the surface oxygen atoms of POMs. The gas sorption profiles showed a much faster
      diffusion for C2H2. All these results suggest that the anion and cation mainly
      play the guest-binding and structure-directing roles, respectively, (i.e.,
      concerted functions) in an ionic crystal with stable three-dimensional
      micropores. 

PMID- 24673449
TI  - EPHA2 Polymorphisms in Estonian Patients with Age-Related Cataract.
AB  - BACKGROUND: Ephrin receptors (Ephs) are tyrosine kinases that together with their
      ligands, ephrins, are considered important in cell-cell communication, especially
      during embryogenesis but also for epithelium homeostasis. Studies have
      demonstrated the involvement of mutations or common variants of the gene encoding
      Eph receptor A2 (EPHA2), in congenital cataract and in age-related cataract. This
      study investigated a number of disease-associated single nucleotide polymorphisms
      (SNPs) in EPHA2 in patients with age-related cataract. MATERIALS AND METHODS: The
      study included 491 Estonian patients who had surgery for age-related cataract,
      classified as nuclear, cortical, posterior subcapsular and mixed lens opacities,
      and 185 controls of the same ethnical origin. Seven SNPs in EPHA2 (rs7543472,
      rs11260867, rs7548209, rs3768293, rs6603867, rs6678616, rs477558) were genotyped
      using TaqMan Allelic Discrimination. Statistical analyses for single factor
      associations used chi(2)-test and logistic regression was performed including
      relevant covariates (age, sex and smoking). RESULTS: In single-SNP allele
      analysis, only the rs7543472 showed a borderline significant association with
      risk of cataract (p = 0.048). Regression analysis with known risk factors for
      cataract showed no significant associations of the studied SNPs with cataract.
      Stratification by cataract subtype did not alter the results. Adjusted odds
      ratios were between 0.82 and 1.16 (95% confidence interval 0.61-1.60).
      CONCLUSIONS: The present study does not support a major role of EphA2 in
      cataractogenesis in an Estonian population.

PMID- 24673451
TI  - A general Suzuki cross-coupling reaction of heteroaromatics catalyzed by
      nanopalladium on amino-functionalized siliceous mesocellular foam.
AB  - Suzuki-Miyaura cross-coupling reactions of heteroaromatics catalyzed by palladium
      supported in the cavities of amino-functionalized siliceous mesocellular foam are
      presented. The nanopalladium catalyst effectively couples not only heteroaryl
      halides with boronic acids but also heteroaryl halides with boronate esters,
      potassium trifluoroborates, MIDA boronates, and triolborates, producing a wide
      range of heterobiaryls in good to excellent yields. Furthermore, the
      heterogeneous palladium nanocatalyst can easily be removed from the reaction
      mixture by filtration and recycled several times with minimal loss in activity.
      This catalyst provides an alternative, environmentally friendly, low-leaching
      process for the preparation of heterobiaryls. 

PMID- 24673452
TI  - Role of MDM2 T309G polymorphism in susceptibility and prognosis of nonsmall cell
      lung cancer: a meta-analysis.
AB  - AIMS: This meta-analysis was performed to evaluate the relationships of a common
      polymorphism (T309G, rs2279744 T>G) in the murine double minute 2 (MDM2) gene
      with susceptibility and prognosis of nonsmall cell lung cancer (NSCLC). METHODS:
      The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane
      Library, and CBM databases were searched for relevant articles published before
      November 1st, 2013 without any language restrictions. Meta-analysis was conducted
      using the STATA 12.0 software. Crude odds ratios (ORs) or hazard risk (HR) with
      their 95% confidence intervals (95% CI) were calculated. Seven clinical studies
      with a total 3732 NSCLC patients and 1472 healthy controls met the inclusion
      criteria. RESULTS: The results of our meta-analysis suggested that MDM2 T309G
      polymorphism might be strongly correlated with an increased risk of NSCLC (G
      allele vs. T allele: OR=1.63, 95% CI: 1.42-1.89, p<0.001; TG+GG vs. TT: OR=1.54,
      95% CI: 1.31-1.80, p<0.001; respectively). Furthermore, we observed significant
      associations of MDM2 T309G polymorphism with poor overall survival (TT vs. GT:
      HR=1.22, 95% CI: 101-1.43, p<0.001; TT vs. GG: HR=1.31, 95% CI: 1.04-1.59,
      p<0.001; TT vs. GT+GG: HR=1.44, 95% CI: 1.13-1.76, p<0.001; respectively) and
      progression-free survival (TT vs. GT+GG: HR=1.26, 95% CI: 0.82-1.69, p<0.001) of
      NSCLC patients. CONCLUSIONS: Our findings provide convincing evidence that the
      MDM2 T309G polymorphism may contribute to individual differences in NSCLC
      susceptibility and prognosis. Thus, the MDM2 T309G polymorphism may be a
      promising potential biomarker for NSCLC diagnosis and prognosis.

PMID- 24673453
TI  - An evolutionary perspective on reproductive individual heterogeneity in a marine
      vertebrate.
AB  - Although the quantification of individual heterogeneity in wild populations'
      vital rates has recently attracted growing interest among ecologists, the
      investigation of its evolutionary consequences remains limited, mainly because of
      the difficulties in assessing fitness and heritability from field studies on free
      ranging animals. In the presence of individual variability, evaluation of fitness
      consequences can notably be complicated by the existence of trade-offs among
      different vital rates. In this study, to further assess the evolutionary
      significance of previously quantified levels of individual heterogeneity in
      female Weddell seal (Leptonychotes weddellii Lesson) reproductive rates (Chambert
      et al. ), we investigated how several life-history characteristics of female
      offspring were related to their mother's reproductive rate, as well as to other
      maternal traits (age and experience) and environmental conditions at birth. The
      probability and age of first reproduction (recruitment) of female offspring was
      not related to their mother's reproductive rate, suggesting the absence of a
      maternal trade-off between the number and quality of offspring a female produces.
      Evidence of a positive, but relatively weak, relationship between the
      reproductive rates of a mother and her female offspring was found, suggesting
      some degree of heritability in this trait. Using a simulation approach based on
      these statistical findings, we showed that substantial differences in the number
      of grandchildren, produced through female progeny, can be expected among females
      with different reproductive rates. Despite the presence of substantial stochastic
      variability, due to environmental fluctuations and other unidentified mechanisms,
      and in the light of the fact that the metrics obtained do not provide a full
      measure of real fitness, our results do suggest that the individual reproductive
      variability found in female Weddell seals could potentially have important
      fitness consequences. 

PMID- 24673454
TI  - Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism
      contributing to decreased platelet count.
AB  - The pathophysiological mechanisms contributing to the decreased platelet count in
      immune thrombocytopenia (ITP) are not entirely understood. Here, we investigated
      the key step of proplatelet formation (PPF) by studying the effect of ITP plasma
      in thrombopoiesis. Normal cord blood-derived mature megakaryocytes were cultured
      in the presence of recalcified plasma from ITP patients, and PPF was evaluated by
      microscopic analysis. Patient samples induced a dose-dependent inhibition in PPF,
      as well as decreased complexity of proplatelet architecture. Although slightly
      increased, plasma-induced megakaryocyte apoptosis was not related to PPF
      impairment. Purified IgG reproduced the inhibitory effect, while platelet
      adsorbed plasma induced its reversion, suggesting the involvement of auto
      antibodies in the inhibition of thrombopoiesis. Impaired PPF, induced by ITP
      plasmas bearing anti-GPIIb-IIIa antibodies, was related to their ability to
      interfere with the normal function of this integrin, as assessed by megakaryocyte
      PAC-1 binding and beta3 integrin phosphorylation while the presence of anti
      glycoprotein Ia-IIa auto-antibodies was associated with loss of normal inhibition
      of PPF induced by type I collagen. In conclusion, abnormal thrombopoiesis
      comprising decreased PPF and morphological changes in proplatelet structure are
      induced by patient samples, unveiling new mechanisms contributing to decreased
      platelet count in ITP. 

PMID- 24673455
TI  - Abnormalities of quantities and functions of linker for activations of T cells in
      severe aplastic anemia.
AB  - OBJECTIVE: Severe aplastic anemia (SAA) is a rare immune-regulated disease
      characterized by severe pancytopenia and bone marrow failure, caused by
      destruction of hematopoietic cells by the activated T lymphocytes. Linker for
      activation of T cells (LAT), a transmembrane adaptor protein, plays a key role in
      T-cell and mast cell functions. However, it remains unclear how LAT may change in
      patients with SAA. This study aims at understanding the role of lymphocyte LAT in
      SAA. METHODS: The expression of LAT, related signaling molecules, and T-cell
      effector molecules was determined by flow cytometry. LAT mRNA was evaluated by
      quantitative real-time PCR. Cytokine production by cultured T cells was
      determined by ELISA. RESULTS: Patients with SAA had an increased levels of LAT
      and both total phosphorylated LAT and of the related molecule (ZAP-70) in
      circulating T cells compared with normal controls. In patients with SAA, the
      expression of LAT was positively associated with the expression of perforin and
      granzyme B in CD8(+) T cells. Inhibition of LAT expression in T cells from
      patients with SAA decreased the activation of the CD4(+) and CD8(+) T-cell
      subsets. Overexpression of LAT in T cells from normal controls increased the
      activation of CD4(+) and CD8(+) T-cell subsets with increased apoptosis of K562
      cells in coculture. CONCLUSIONS: Our findings demonstrate that dysregulation of
      LAT expression and activation may contribute to over-function of T cells,
      imbalance of Th1/Th2 subsets and thus lead to hematopoiesis failure in SAA.
      Immunosuppressive therapy dramatically reduced the expression of LAT making it an
      attractive therapeutic target in SAA.

PMID- 24673456
TI  - Loading of nuclear autoantigens prototypically recognized by systemic lupus
      erythematosus sera into late apoptotic vesicles requires intact microtubules and
      myosin light chain kinase activity.
AB  - Most cases of systemic lupus erythematosus (SLE) are characterized by an impaired
      clearance of apoptotic cells in various tissues. Non-cleared apoptotic waste is
      considered an immunogen driving the autoimmune response in patients with SLE.
      During the execution of apoptosis, membrane blebs are formed and filled with
      cellular components. Here, we evaluate the cytoskeletal pathway(s) responsible
      for the loading of SLE prototypic nuclear autoantigens into the apoptotic cell
      derived membranous vesicles (ACMV) generated during late phases of apoptosis.
      HeLa cells expressing a fusion protein of histone H2B with green fluorescent
      protein (GFP) were irradiated with ultraviolet (UV)-B to induce apoptosis. The
      appearance and trafficking of chromatin-derived material was monitored by
      fluorescence microscopy. Specific inhibitors of cytoskeletal pathways were
      employed to identify the motile elements involved in translocation and
      trafficking of the nuclear components. We observed that immediately after their
      appearance the ACMV did not contain histone H2B(GFP) ; in this phase the
      fluorescence was contained in the nuclear remnants and the cytoplasm. Within
      consecutive minutes the ACMV were loaded with chromatin-derived material, whereas
      the loading of simultaneously created ACMV with histone H2B(GFP) was not uniform.
      Some ACMV were preferentially filled and, consequently, showed a remarkably
      higher histone H2B(GFP) accumulation. Inhibitors of the cytoskeleton revealed
      that functional microtubules and myosin light chain kinase are required for
      nuclear shrinkage and loading of nuclear material into the ACMV, respectively. 

PMID- 24673457
TI  - Roundabout 1 exists predominantly as a basal dimeric complex and this is
      unaffected by binding of the ligand Slit2.
AB  - Robo (Roundabout) receptors and their Slit polypeptide ligands are known to play
      key roles in neuronal development and have been implicated in both angiogenesis
      and cancer. Like the other family members, Robo1 is a large single transmembrane
      domain polypeptide containing a series of well-defined extracellular elements.
      However, the intracellular domain lacks structural definition and little is known
      about the quaternary structure of Robo receptors or how binding of a Slit might
      affect this. To address these questions combinations of both autofluorescent
      protein-based FRET imaging and time-resolved FRET were employed. Both approaches
      identified oligomeric organization of Robo1 that did not require the presence of
      the intracellular domain. SpIDA (spatial intensity distribution analysis) of eGFP
      tagged forms of Robo1 indicated that for a C-terminally deleted version
      approximately two-thirds of the receptor was present as a dimer and one-third as
      a monomer. By contrast, full-length Robo1 was present almost exclusively as a
      dimer. In each case this was unaffected by the addition of Slit2, although
      parallel studies demonstrated the biological activity of Slit2 and its
      interaction with Robo1. Deletion of both the immunoglobulin and fibronectin type
      III extracellular repeats prevented dimer formation, with the immunoglobulin
      repeats providing the bulk of the protein-protein interaction affinity. 

PMID- 24673459
TI  - Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of
      contrast-induced nephropathy after computed tomography.
AB  - Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute
      kidney injury (AKI) and a source of significantly increased short- and long-term
      mortality. Studies of large cohorts have revealed that more than half of these
      cases are in subjects undergoing cardiac catheterization and intra-arterial
      coronary angiography, and nearly a third follow computed tomography (CT) scans.
      Neutrophil gelatinase-associated lipocalin (NGAL) represents an early predictive
      troponin-like biomarker for AKI. Its role in the timely diagnosis of CIN has
      already been examined in adults and children undergoing coronary angiography and
      a meta-analysis revealed a very good performance of plasma or urine NGAL in the
      prediction of CIN. Much of these data have been extrapolated to patients
      receiving intravenous (IV) contrast agent for CT scans, although major
      differences in patient populations, contrast volume administered and intra
      procedural complications between the two settings exist. In this context, a
      recent prospective study by our group evaluated plasma NGAL, measured using
      standardized Tauriage(r) NGAL test (Biosite Incorporated, San Diego, CA) at
      baseline and 6-h post-procedure, for early detection of CIN among hospitalized
      patients undergoing elective contrast-enhanced CT. CIN, defined as an increase in
      serum creatinine (SCr) of >25% or >0.5 mg/dL from baseline within 48-h post
      procedure, was found in 8.51% of subjects. In contrast, significant elevation of
      plasma NGAL was found at 6-h post-procedure with excellent performance
      characteristics. This review presents the current status of NGAL in the
      prediction of CIN after IV contrast administration among hospitalized patients
      undergoing elective contrast-enhanced CT.

PMID- 24673458
TI  - The CXCR4 and adhesion molecule expression of CD34+ hematopoietic cells mobilized
      by "on-demand" addition of plerixafor to granulocyte-colony-stimulating factor.
AB  - BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is routinely used for
      mobilization of hematopoietic stem and progenitor cells preceding autologous
      transplantation after high-dose chemotherapy in hematologic malignancies.
      However, due to high mobilization failure rates, alternative mobilization
      strategies are required. STUDY DESIGN AND METHODS: Patients who poorly mobilized
      CD34+ hematopoietic cells (HCs) with G-CSF additionally received the CXCR4
      antagonist plerixafor. The phenotype of CD34+ HCs collected after this plerixafor
      induced "rescue" mobilization, in regard to adhesion molecule and CD133, CD34,
      and CD38 expression in comparison to CD34+ HCs collected after traditional G-CSF
      administration in good mobilizers, was analyzed flow cytometrically. To confirm
      previous studies in our patient cohort, the efficiency of mobilization and
      subsequent engraftment after this "on-demand" plerixafor mobilization were
      analyzed. RESULTS: Pronounced mobilization occurred after plerixafor
      administration in poor mobilizers, resulting in similar CD34+ cell yields as
      obtained by G-CSF in good mobilizers, whereby plerixafor increased the content of
      primitive CD133+/CD34+/CD38- cells. The surface expression profiles of the marrow
      homing and retention receptors CXCR4, VLA-4, LFA-1, and CD44 on mobilized CD34+
      cells and hematopoietic recovery after transplantation were similar in patients
      receiving G-CSF plus plerixafor or G-CSF. Unexpectedly, the expression levels of
      respective adhesion receptors were not related to mobilization efficiency or
      engraftment. CONCLUSION: The results show that CD34+ HCs collected by plerixafor
      induced rescue mobilization are qualitatively equivalent to CD34+ HCs collected
      after traditional G-CSF mobilization in good mobilizers, in regard to their
      adhesive phenotype and engraftment potential. Thereby, plerixafor facilitates the
      treatment of poor mobilizers with autologous HC transplantation after high-dose
      chemotherapy.

PMID- 24673460
TI  - Mucinous adenocarcinoma arising from supratentorial intramedullary neuroenteric
      cyst with broncho-pulmonary differentiation.
AB  - Neuroenteric cysts are benign intradural endoderm cysts lined by gastrointestinal
      (GI) or tracheobronchial epithelial cells. Their malignant transformation is
      extremely rare and only six cases have been reported. In these cases, tissue
      lineage of the cystic endoderm cells giving rise to carcinoma was not clearly
      identified either as respiratory or as GI type. Herein, we report a case of
      mucinous adenocarcinoma arising from the neuroenteric cyst with broncho-pulmonary
      differentiation in the right cerebral hemisphere of a Japanese woman in her late
      50s. The cyst wall was entirely lined by the following respiratory epithelial
      components: stratified bronchial ciliated columnar epithelium with basal cells
      positive for CK5 and p63, terminal bronchiolar Clara cells positive for thyroid
      transcription factor (TTF)-1, surfactant B and negative for surfactant C, type I
      pneumocytes positive for TTF-1, negative for surfactant B and C, and type II
      pneumocytes positive for TTF-1 and surfactant B and C. In addition, nests of
      hyperplastic single layered mucinous epithelial cells with bronchial goblet cell
      phenotype were also demonstrated, and histologic features were almost the same as
      the pulmonary type I congenital adenomatoid malformation (CCAM) with mucinous
      epithelial proliferation. The mucinous epithelial nests of type I CCAM are liable
      to develop mucinous adenocarcinoma and frequently accompany K-ras mutation and
      expression of p16. However, K-ras mutation and p-16 expression were not detected
      in this case.

PMID- 24673461
TI  - Innervation of rat and human dura mater and pericranial tissues in the parieto
      temporal region by meningeal afferents.
AB  - OBJECTIVE: To reinvestigate the innervation pattern of the dura mater of rat and
      human middle cranial fossa, the morpho-functional substrate of headache
      generation, and adjacent extracranial tissues with neuronal in vitro tracing.
      BACKGROUND: This study was initiated by recent structural and functional findings
      of meningeal afferent fibers which innervate the cranial dura mater and may
      project to extracranial tissues. METHODS: Anterograde and retrograde neuronal in
      vitro tracing was made in formaldehyde fixed hemisected rat and human skulls. The
      fluorescent tracer DiI was applied to proximally cut meningeal nerves in rat and
      to distal branches of the spinosus nerve in human calvaria lined by dura mater.
      After several weeks, the dura mater and deep extracranial tissues were examined
      with fluorescence microscopy. RESULTS: In addition to a network of meningeal
      nerve fibers, several fiber bundles were observed, leaving the skull through
      emissary canals and fissures to innervate the pericranial temporal, parietal, and
      occipital periosteum. Traced fibers were seen spreading into deep layers of the
      temporal and upper neck muscles. Retrograde neuronal tracing revealed labeled
      cell bodies exclusively in the mandibular and maxillary division of the rat
      trigeminal ganglion, and centrally projecting fibers were identified in the
      spinal trigeminal tract. Electron microscopy of the cross-sected spinosus nerve
      showed myelinated and unmyelinated axons with similar numbers in human and rat.
      CONCLUSIONS: We conclude that a proportion of meningeal afferents innervates
      extracranial tissues like periosteum and pericranial muscles via collaterals
      projecting through the skull. These afferents may be nociceptive, some may
      subserve proprioceptive functions. The finding of extracranial projections of
      meningeal afferents may be important for our understanding of extracranial
      impacts on headache generation and therapy.

PMID- 24673462
TI  - Two new adenosine receptor antagonists for the treatment of Parkinson's disease:
      istradefylline versus tozadenant.
AB  - INTRODUCTION: Adenosine A2A receptors are localized in the brain, mainly within
      the caudate and putamen nuclei of the basal ganglia. Their activation leads to
      stimulation of the 'indirect' pathway. Conversely, administration of A2A receptor
      antagonists leads to inhibition of this pathway, which was translated into
      reduced hypomotility in several animal models of parkinsonism. AREAS COVERED: In
      this review, the effects of two A2A receptor antagonists, istradefylline and
      tozadenant, on parkinsonian symptoms in animal and humans will be discussed.
      EXPERT OPINION: Animal studies have shown potent antiparkinsonian effects for
      several A2A receptor antagonists, including istradefylline. In clinical trials,
      istradefylline reduced OFF time when administered with levodopa, but results are
      inconclusive. Results with tozadenant are scarce. Modification of thalamic blood
      flow compatible with reduced inhibition was noted in one small trial, followed by
      a significant reduction in OFF time in a larger one. Therefore, both drugs show
      promising efficacy for the reduction of OFF time in levodopa-treated Parkinson's
      disease patients, but further research is needed in order to obtain definitive
      conclusions.

PMID- 24673463
TI  - Alternate heteroepitaxial growth of highly oriented organic multilayer films.
AB  - The heterostructure, a basic active unit applied in the device level, plays an
      important role in traditional inorganic optoelectronics. In the organic field,
      although the requirement for the heterostructure is crucial, achievement and
      understanding on the growth and functionality of organic heterostructure are
      still finite, especially for ordered crystalline organic multilayers with smooth
      interfaces. Here a series of highly ordered crystalline heterostructures with
      molecule-level smoothness were obtained from single layer to alternate multilayer
      with a phthalocyanine molecule and a perylene derivative. Well-defined epitaxy
      relationship and crystal alignment were evidenced from the atomic force
      microscopy (AFM), X-ray diffraction (XRD), and transmission electron microscope
      (TEM) results. The evolution of the films reveals that, for organic-organic
      alternate multilayer growth, along with the intrinsic properties of organic
      molecules such as the packing and preferred growth direction, the soft matter
      properties of organic films contribute to well-defined heteroepitaxy despite that
      the lattice mismatch between the two materials' bulk phases is large. Thin film
      phases of the first few layers benefit the grain coalescence and thus the
      formation of smooth films. Potential application is implied from the
      heterojunctions' good transport ability. 

PMID- 24673464
TI  - Effect of the menstrual cycle on inflammatory cytokines in the periodontium.
AB  - BACKGROUND AND OBJECTIVE: The effects of different levels of steroid hormones, as
      experienced during puberty, pregnancy and menopause, on the periodontium have
      been demonstrated, but changes in sex hormone levels during the menstrual cycle,
      and the influence of these changes on the periodontium, remain unresolved. The
      aim of this study was to investigate the effect of the menstrual cycle on the
      levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha) in gingival crevicular fluid and on periodontal clinical parameters,
      including the gingival bleeding index (GBI) and the modified gingival index
      (MGI), in periodontally healthy women. MATERIAL AND METHODS: Twenty-seven
      periodontally healthy women with a regular menstrual cycle were included in the
      study. Clinical parameters, including the GBI, the MGI and the simplified oral
      health index, were recorded during menstruation, ovulation and premenstruation
      phases (e.g. on days 1-2, 12-14 and 22-24, respectively) of the menstrual cycle.
      Gingival crevicular fluid and unstimulated saliva were collected, at each study
      phase, for assessment of IL-1beta, TNF-alpha, estrogen and progesterone. RESULTS:
      Both the GBI and the MGI increased significantly during the menstrual cycle, and
      were significantly higher during ovulation than during menstruation or
      premenstruation (p < 0.001). No significant change in the simplified oral health
      index was observed during the menstrual cycle ( p = 0.18). The levels of IL-1beta
      and TNF-alpha increased during the different phases of the menstrual cycle, but
      only the change in the TNF-alpha concentration was significant ( p < 0.05).
      CONCLUSION: This study indicated that changes occurring during the menstrual
      cycle influence the periodontium and induce inflammatory conditions.

PMID- 24673465
TI  - Classification, diagnosis, and approach to treatment for angioedema: consensus
      report from the Hereditary Angioedema International Working Group.
AB  - Angioedema is defined as localized and self-limiting edema of the subcutaneous
      and submucosal tissue, due to a temporary increase in vascular permeability
      caused by the release of vasoactive mediator(s). When angioedema recurs without
      significant wheals, the patient should be diagnosed to have angioedema as a
      distinct disease. In the absence of accepted classification, different types of
      angioedema are not uniquely identified. For this reason, the European Academy of
      Allergy and Clinical Immunology gave its patronage to a consensus conference
      aimed at classifying angioedema. Four types of acquired and three types of
      hereditary angioedema were identified as separate forms from the analysis of the
      literature and were presented in detail at the meeting. Here, we summarize the
      analysis of the data and the resulting classification of angioedema. 

PMID- 24673466
TI  - Multiple roles of Equarin during lens development.
AB  - Since the days of Hans Spemann, the ocular lens has served as one of the most
      important developmental systems for elucidating the fundamental processes of
      induction and differentiation. Lens is an important source of signals that
      influence the eye development and a variety of genes expressed by the lens have
      been identified. The identification of additional molecule(s), especially
      secreted ones that might mediate signals, will extend our knowledge of the
      molecular mechanisms of eye and lens development. Here, we will introduce a
      soluble molecule, Equarin, and discuss its vital role in multiple aspects of lens
      development.

PMID- 24673467
TI  - Management of shortened dental arches and periodontal health: 5-year results of a
      randomised trial.
AB  - In a multicentre randomised trial (German Research Association, grants DFG WA
      831/2-1 to 2-6, WO 677/2-1.1 to 2-2.1.; controlled-trials.com ISRCTN97265367),
      patients with complete molar loss in one jaw received either a partial removable
      dental prosthesis (PRDP) with precision attachments or treatment according to the
      SDA concept aiming at pre-molar occlusion. The objective of this current analysis
      was to evaluate the influence of different treatments on periodontal health.
      Linear mixed regression models were fitted to quantify the differences between
      the treatment groups. The assessment at 5 years encompassed 59 patients (PRDP
      group) and 46 patients (SDA group). For the distal measuring sites of the
      posterior-most teeth of the study jaw, significant differences were found for the
      plaque index according to Silness and Loe, vertical clinical attachment loss (CAL
      V), probing pocket depth (PPD) and bleeding on probing. These differences were
      small and showed a slightly more unfavourable course in the PRDP group. With CAL
      V and PPD, significant differences were also found for the study jaw as a whole.
      For CAL-V, the estimated group differences over 5 years amounted to 0.27 mm (95%
      CI 0.05; 0.48; P = 0.016) for the study jaw and 0.25 mm (95% CI 0.05; 0.45; P =
      0.014) for the distal sites of the posterior-most teeth. The respective values
      for PPD were 0.22 mm (95% CI 0.03; 0.41; P = 0.023) and 0.32 mm (95% CI 0.13;
      0.5; P = 0.001). It can be concluded that even in a well-maintained.patient group
      statistically significant although minor detrimental effects of PRDPs on
      periodontal health are measurable.

PMID- 24673469
TI  - Chelation-assisted hydroesterification of alkenes: new ruthenium catalyst systems
      and ligand effects.
AB  - New types of ruthenium catalysts were developed for the chelation-assisted
      intermolecular olefin hydroesterification that employs 2-pyridylmethyl formate as
      an ester source. Two classes of ligands, NHCs and phosphines, were found to
      facilitate the reaction delivering isomeric ester products (linear versus
      branched) with different ratios, thus allowing access to ligand-guided selective
      hydroesterification. 

PMID- 24673468
TI  - Genetic variants in KDR transcriptional regulatory region affect promoter
      activity and intramuscular fat deposition in Erhualian pigs.
AB  - Kinase insert domain receptor (KDR), a vascular endothelial growth factor (VEGF)
      receptor, is widely regarded as having a principal role in mediating VEGF-induced
      responses in angiogenesis. As angiogenesis provides oxygen and nutrients for
      growth and deposition of adipose cells, our objective was to determine whether
      the promoter polymorphisms in the KDR gene have effects on intramuscular fat
      (IMF) deposition in the longissimus dorsi muscle. Three novel SNPs, c.-1316A>G,
      c.-1303C>T and c.-1108A>C, were revealed to have differential allele distribution
      between high- and low-IMF content groups by comparative sequencing of DNA pools.
      The three SNPs were completely linked, forming only ACA or GTC haplotypes when
      genotyped in 105 Erhualian purebred pigs and 98 Duroc * Large White * Yorkshire
      (D*L*Y) cross-bred pigs. It is interesting that the ACA haplotype is present
      exclusively in Erhualian pigs and not in D*L*Y pigs. The ACA promoter was found
      to have higher activity than GTC type for KDR transcription using either gene
      expression analysis or luciferase assay. Site-direct mutation analysis
      demonstrated that c.-1316A>G is the causation of promoter activity alteration.
      Furthermore, we detected that CD31 (also known as PECAM1) and CD34, two blood
      vessel endothelial markers, expressed higher in ACA/ACA individuals. We concluded
      that the ACA promoter might be a desirable form for improving IMF content by
      promoting higher KDR gene expression and more blood vessel network.

PMID- 24673470
TI  - Therapeutic plasma exchange and intravenous immunoglobulin as primary therapy for
      D alloimmunization in pregnancy precludes the need for intrauterine transfusion.
AB  - BACKGROUND: Maternal D alloimmunization detected in early gestation requires
      aggressive intervention to prevent severe fetal anemia. An intrauterine
      transfusion (IUT) is indicated to prevent fetal death once severe fetal anemia
      has been detected, but is not without risk. Protocols combining therapeutic
      plasma exchange (TPE) and intravenous immunoglobulin (IVIG) have been described,
      but they usually bridge to IUT. STUDY DESIGN AND METHODS: We describe a 27-year
      old G4, P0-1-2-0 Caucasian female with a history of ruptured ectopic pregnancy
      presented at 12 weeks' gestation with a very high anti-D titer (2048). TPE was
      performed on that week and twice more in the following week, with a fourth final
      exchange during Week 14. A loading dose of IVIG (2 g/kg) was administered over 2
      days after the third TPE and then 1 g/kg per week until Week 28 (total, 14
      doses). RESULTS: The antibody titer decreased to 256 by the beginning of 15
      weeks' gestation and remained stable at that level for the remainder of the
      pregnancy. Doppler ultrasonographic measurements of the fetal middle cerebral
      artery peak flow velocity performed throughout gestation showed no evidence of
      fetal anemia. A healthy male infant was delivered at 37 weeks' gestation with
      mild immune-mediated hemolysis. The infant underwent successful treatment with an
      IVIG dose of 750 mg/kg and a red blood cell exchange. CONCLUSION: Our unique TPE
      IVIG protocol was successful at preventing the onset of severe fetal anemia in a
      patient with high titer anti-D. Since IUT may be fatal, our approach offers a
      safer and less-invasive treatment regime that can adequately sustain a fetus
      until term.

PMID- 24673471
TI  - From autophagy to senescence and apoptosis in Angiotensin II-treated vascular
      endothelial cells.
AB  - The aim of this study was to explore if cell autophagy is activated by AngII
      before aging using human umbilical vascular endothelial cells (HUVECs). The
      ultrastructural analysis of HUVECs was performed to observe autophagosomes. The
      LC3-II/LC3-I ratio was determined by western blot assay. The beta-gal staining
      was used to identify cell senescence. The flow cytometry was performed to
      evaluate cell apoptosis. The BH3 domain analog ABT737 or Beclin-1 knockdown by
      specific shRNA or valsartan was applied to investigate their effects on cell
      autophagy, senescence, and apoptosis induced by Ang II. Cell autophagy was
      initiated after Ang II treatment at 24 h. And cell senescence and apoptosis were
      observed in Ang II-treated cells at 48 h. The significant interaction of Beclin-1
      and Bcl-2 was detected at 48 h after Ang II treatment. Beclin-1 was indispensable
      to Ang II-induced autophagy, and its BH3 domain was required for the interaction
      with Bcl-2 to attenuate autophagy. Pretreated with valsartan, cells were present
      with less autophagic, senescent, and apoptotic cells after Ang II stimulation. In
      conclusion, Ang II induced autophagy, senescence, and apoptosis of HUVECs
      progressively, and autophagy presented an early protective effect on vascular
      endothelial damage due to Ang II. 

PMID- 24673472
TI  - Basophilic inclusions and neuronal intermediate filament inclusions in
      amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
AB  - Basophilic inclusions (BIs) and neuronal intermediate filament inclusions (NIFIs)
      are key structures of basophilic inclusion body disease and neuronal intermediate
      filament inclusion disease (NIFID), respectively. BIs are sharply-defined, oval
      or crescent neuronal intracytoplasmic inclusions that appear pale blue-gray in
      color with HE staining and purple in color with Nissl but are stained poorly with
      silver impregnation techniques. Immunohistochemically BIs are negative for tau,
      trans-activation response DNA 43 (TDP-43), alpha-synuclein, neurofilament (NF)
      and alpha-internexin, positive for p62, and variably ubiquitinated. Noticeably,
      BIs are consistently fused in sarcoma (FUS) positive. NIFIs are by definition
      immuno-positive for class IV IFs including three NF triplet subunit proteins and
      alpha-internexin but negative for tau, TDP-43, and alpha-synuclein. In NIFID
      cases several types of inclusions have been identified. Among them, hyaline
      conglomerate-like inclusions are the only type that meets the above
      immunohistochemical features of NIFIs. This type of inclusion appears upon HE
      staining as multilobulated, faintly eosinophilic or pale amphophilic spherical
      masses with a glassy appearance. These hyaline conglomerates appear strongly
      argyrophilic, and robustly and consistently immuno-positive for IFs. In contrast,
      this type of inclusion shows no or only occasional dot-like FUS immunoreactivity.
      Therefore, BIs and NIFIs are distinct from each other in terms of morphological,
      tinctorial and immunohistochemical features. However, basophilic inclusion body
      disease (BIBD) and NIFID are difficult to differentiate clinically. Moreover,
      Pick body-like inclusions, the predominant type of inclusions seen in NIFID, are
      considerably similar to the BIs of BIBD in that this type of inclusion is
      basophilic, poorly argyrophilic, negative for IFs and intensely immuno-positive
      for FUS. As BIBD and NIFID share FUS accumulation as the most prominent molecular
      pathology, whether these two diseases are discrete entities or represent a
      pathological continuum remains a question to be answered. 

PMID- 24673473
TI  - Evaluation of a Polyethylene Glycol-Osteogenic Protein-1 System on Alveolar Bone
      Regeneration in the Mini-Pig.
AB  - Alveolar bone regeneration associated with the local release of osteogenic
      protein-1 (OP-1) from a polyethylene glycol (PEG) scaffold was evaluated in 14
      mini-pigs. Following extraction of mandibular teeth and 26-weeks of healing time,
      standardized bone defects were created bilaterally in the posterior mandibles (3
      sites for each hemimandible) that were randomly assigned to treatment groups.
      Seven treatments groups were compared: 4 different concentrations of the PEG/OP-1
      test system (n = 14 for each), a positive control (collagen/OP-1, n = 14), a
      negative control (PEG only, n = 7) and nontreated defects (n = 7). Each animal
      provided all test and control groups. The animals were sacrificed after 3 weeks
      of healing and samples were processed for histology and histomorphometry. Three
      weeks after implantation, there were positive clinical responses for all test
      groups. Earlier bone maturation was observed in the test groups that had higher
      concentrations of OP-1 (0.25, 0.5, or 1 mg/mL) compared to the negative control
      group (PEG alone), the low concentration group (0.1 mg/mL), and the positive
      control group (collagen/OP-1). However, histomorphometric quantitative analyses
      did not reveal any statistical difference between any of the groups. No residual
      PEG biomaterial or inflammatory responses to the biomaterial or growth factor
      were observed. This study confirmed the safe local delivery of OP-1 from PEG
      hydrogel. Alveolar bone regeneration was not statistically different between
      tests groups, negative control (PEG alone) or commercial positive control
      (collagen/OP-1). The semi-quantitative analysis, however, showed a trend in favor
      of the higher concentrations of OP-1 to induce faster bone maturation. 

PMID- 24673474
TI  - Assessment of the effects of antihistamine drugs on mood, sleep quality,
      sleepiness, and dream anxiety.
AB  - OBJECTIVE: There are limited comparative studies on classic and new-generation
      antihistamines that affect sleep quality and mood. The purpose of this study was
      to determine and compare the effects of classic and new-generation antihistamines
      on sleep quality, daytime sleepiness, dream anxiety, and mood. METHODS: Ninety
      two patients with chronic pruritus completed study in the dermatology outpatient
      clinic. Treatments with regular recommended therapeutic doses were administered.
      The effects of antihistaminic drugs on mood, daytime sleepiness, dream anxiety,
      and sleep quality were assessed on the first day and 1 month after. RESULTS:
      Outpatients who received cetirizine and hydroxyzine treatments reported higher
      scores on the depression, anxiety, and fatigue sub-scales than those who received
      desloratadine, levocetirizine, and rupatadine. Pheniramine and rupatadine were
      found to be associated with daytime sleepiness and better sleep quality. UKU side
      effects scale scores were significantly elevated among outpatients receiving
      pheniramine. Classic antihistamines increased daytime sleepiness and decreased
      the sleep quality scores. New-generation antihistamines reduced sleep latency and
      dream anxiety, and increased daytime sleepiness and sleep quality. CONCLUSION:
      Both antihistamines, significantly increased daytime sleepiness and nocturnal
      sleep quality. Daytime sleepiness was significantly predicted by rupadatine and
      pheniramine treatment. Cetirizine and hydroxyzine, seem to have negative
      influences on mood states. Given the extensive use of antihistamines in clinical
      settings, these results should be more elaborately examined in further studies.

PMID- 24673475
TI  - Postprandial lipemia as a cardiometabolic risk factor.
AB  - High levels of fasting circulating triglycerides (TG) represent an independent
      risk factor for cardiovascular disease. In western countries, however, people
      spend most time in postprandial conditions, with continuous fluctuation of
      lipemia due to increased levels of TG-rich lipoproteins (TRLs), including
      chylomicrons (CM), very low density lipoproteins (VLDL), and their remnants.
      Several factors contribute to postprandial lipid metabolism, including dietary,
      physiological, pathological and genetic factors. The presence of coronary heart
      disease, type 2 diabetes, insulin resistance and obesity is associated with
      higher postprandial TG levels compared with healthy conditions; this association
      is present also in subjects with normal fasting TG levels. Increasing evidence
      indicates that impaired metabolism of postprandial lipoproteins contributes to
      the pathogenesis of coronary artery disease, suggesting that lifestyle
      modifications as well as pharmacological approaches aimed at reducing
      postprandial TG levels might help to decrease the cardiovascular risk.

PMID- 24673476
TI  - The choice to access outdoor areas affects the behavior of great apes.
AB  - Outdoor access is often cited as a critical component of appropriate housing for
      great apes in captivity, and although studies have shown that offering primates
      choices can improve welfare, choice to access specific areas has been empirically
      neglected. Behavioral data were collected on chimpanzees and gorillas housed in
      naturalistic enclosures while (a) restricted to an indoor enclosure and (b)
      permitted free access to an adjacent outdoor area. To isolate the factor of
      choice, only the sessions in which apes remained indoors were compared. With
      choice, chimpanzees showed more frequent social, F(1, 5) = 20.526, p = .006, and
      self-directed behaviors, F(1, 5) = 13.507, p = .014, and lower inactivity levels,
      F(1, 5) = 9.239, p = .029. Gorillas were more frequently inactive, F(1, 8) =
      22.259, p = .002, and produced lower levels of object manipulation, F(1, 8) =
      8.243, p = .021, and feeding, F(1, 8) = 5.407, p = .049. Results are consistent
      with an association between choice and the expression of species-typical and
      arousal behaviors in chimpanzees. The effects are less evident in gorillas, but
      this outcome may be buffered by the species' lower motivation to utilize the
      outdoor spaces. Findings highlight species-specific reactions to access to choice
      that may offer insight for enclosure design, management, and nonhuman animal
      welfare. 

PMID- 24673477
TI  - Hybrid molecules inhibiting myeloperoxidase activity and serotonin reuptake: a
      possible new approach of major depressive disorders with inflammatory syndrome.
AB  - OBJECTIVES: Major depressive disorder (MDD) is accompanied with an imbalance in
      the immune system and cardiovascular impairments, such as atherosclerosis.
      Several mechanisms have been pointed out to underlie this rather unexpected
      association, and among them the activity of myeloperoxidase (MPO). The aim of our
      study was to find compounds that inhibit both MPO and serotonin transporter
      (SERT) for treating MDD associated with cardiovascular diseases. METHODS: SERT
      inhibition was assessed with measuring of [(3) H]-serotonin uptake using HEK-293
      MSR cells. MPO inhibition was determined by taurine chloramine test on 3
      (aminoalkyl)-5-fluoroindole derivatives and on clinically relevant
      antidepressants. All kinetic measurements were performed using a temperature
      controlled stopped-flow apparatus (model SX-18 MV). Promising lead compounds were
      docked onto SERT 3D structure modelled using the LeuT structure complexed to
      tryptophan (PDB code 3F3A). Their toxicological profile was also assessed. KEY
      FINDINGS: 3-(aminoalkyl)-5-fluoroindole derivative with 5 carbons on the side
      chain and paroxetine showed the best activity on both MPO and SERT at the
      nanomolar range. Paroxetine was found to be the first irreversible MPO inhibitor
      at nanomolar concentrations. CONCLUSIONS: Our results put forward the first
      hybrid molecule (compound 25) and drug (paroxetine) that can be especially used
      in MDD associated with inflammatory syndrome.

PMID- 24673478
TI  - Seven novel MHC class I alleles identified in Cercopithecus mitis.
AB  - We report here the identification of three Cemi-A and four Cemi-B novel alleles
      of Cercopithecus mitis. 

PMID- 24673479
TI  - Life-history diversity and its importance to population stability and persistence
      of a migratory fish: steelhead in two large North American watersheds.
AB  - Life-history strategies can buffer individuals and populations from environmental
      variability. For instance, it is possible that asynchronous dynamics among
      different life histories can stabilize populations through portfolio effects.
      Here, we examine life-history diversity and its importance to stability for an
      iconic migratory fish species. In particular, we examined steelhead (Oncorhynchus
      mykiss), an anadromous and iteroparous salmonid, in two large, relatively
      pristine, watersheds, the Skeena and Nass, in north-western British Columbia,
      Canada. We synthesized life-history information derived from scales collected
      from adult steelhead (N = 7227) in these watersheds across a decade. These
      migratory fishes expressed 36 different manifestations of the anadromous life
      history strategy, with 16 different combinations of freshwater and marine ages,
      7.6% of fish performing multiple spawning migrations, and up to a maximum of four
      spawning migrations per lifetime. Furthermore, in the Nass watershed, various
      life histories were differently prevalent through time - three different life
      histories were the most prevalent in a given year, and no life history ever
      represented more than 45% of the population. These asynchronous dynamics among
      life histories decreased the variability of numerical abundance and biomass of
      the aggregated population so that it was > 20% more stable than the stability of
      the weighted average of specific life histories: evidence of a substantial
      portfolio effect. Year of ocean entry was a key driver of dynamics; the median
      correlation coefficient of abundance of life histories that entered the ocean the
      same year was 2.5 times higher than the median pairwise coefficient of life
      histories that entered the ocean at different times. Simulations illustrated how
      different elements of life-history diversity contribute to stability and
      persistence of populations. This study provides evidence that life-history
      diversity can dampen fluctuations in population abundances and biomass via
      portfolio effects. Conserving genetic integrity and habitat diversity in these
      and other large watersheds can enable a diversity of life histories that
      increases population and biomass stability in the face of environmental
      variability. 

PMID- 24673480
TI  - Variation in the CYP2D6 genotype is not associated with carvedilol dose changes
      in patients with heart failure.
AB  - WHAT IS KNOWN AND OBJECTIVE: Carvedilol is the standard of care for heart failure
      (HF) patients. Carvedilol is partially metabolized by the highly polymorphic
      enzyme, CYP2D6. To reach an effective dose while avoiding adverse drug reactions
      (ADRs), testing of CYP2D6 genotype prior to carvedilol initiation may be
      considered. The objectives of this study were to determine CYP2D6 metabolic
      genotypes in an Israeli cohort of HF patients and to investigate the relationship
      between genotype, carvedilol dose and number of ADRs to determine the importance
      of CYP2D6 genotyping prior to treatment initiation. METHODS: Ninety-three
      patients with HF on carvedilol were CYP2D6 genotyped and classified as poor (PM),
      intermediate (IM), extensive (EM) or ultrarapid (UM) metabolizers. Carvedilol
      dose and ADRs were calculated and correlated with genotype using linear
      regression statistic analysis. RESULTS AND DISCUSSION: The distribution of the
      CYP2D6 phenotype in the Israeli population with HF is similar to the European
      general population. There were no significant differences of carvedilol dose and
      number of ADRs among genotype groups. Genotype group affiliation and number of
      adverse drug reactions were not predictive of carvedilol dose changes. WHAT IS
      NEW AND CONCLUSION: Genotype group affiliation and number of adverse drug
      reactions were not predictive of carvedilol dose during therapy for patients with
      HF. The Israeli CYP2D6 phenotype distribution in HF patients was consistent with
      the frequency in the general European population.

PMID- 24673481
TI  - Prognostic significance of soft tissue extension, international prognostic index,
      and multifocality in primary bone lymphoma: a single institutional experience.
AB  - Primary bone lymphoma (PBL) is a rare disease. The literature is inconsistent in
      regard to definition, stage and prognostic factors. We examined the PBL cases
      seen at the Moffitt Cancer Center between 1998 and 2013 using the 2013 World
      Health Organization criteria for bone/soft tissue tumours. Seventy PBL patients
      were included, of whom 53 (75.7%) patients were histologically classified as
      primary bone diffuse large B-cell lymphoma (PB-DLBCL). Femur was the most
      commonly involved site in PBLs with unifocal bone lesions, whereas PBLs with
      multifocal bone lesions most frequently presented with spine disease. Further
      analysis of the PB-DLBCL subgroup showed that these patients had 3- and 5-year
      progression-free survival (PFS) of 61.2% and 46.9%, respectively and 5- and 10
      year overall survival (OS) of 81.1% and 74.7%, respectively. Multivariate
      analysis identified soft tissue extension and International Prognostic Index
      (IPI) score as the most important unfavourable prognostic factors for both PFS
      and OS. Multifocality was also highly significantly associated with a worse PFS
      (P = 0.002) and OS (P < 0.001), although it was not identified in multivariate
      analysis due to its incorporation into the IPI. The results warrant further
      investigation regarding whether PBL with multifocal bone lesions could be
      considered as a systemic and more aggressive disease rather than a conventional
      PBL.

PMID- 24673483
TI  - Spherical-to-cylindrical transformation of reverse micelles and their templating
      effect on the growth of nanostructures.
AB  - We discuss a complete mechanistic study on the anisotropic growth of zinc oxalate
      nanostructures within reverse micelles. We have employed small-angle X-ray
      scattering (SAXS), dynamic light scattering (DLS), and transmission electron
      microscopy (TEM) to understand the detailed growth of the nanostructures. We have
      been able to observe the generation of nuclei and their aggregation to a critical
      size beyond which they form nanostructures of higher dimensions in self-assembled
      templates. One of our aims was to find a correlation between size and shape of
      microemulsion droplets (MDs) and that of the resulting nanostructures of zinc
      oxalate (ZO) which grow within the MDs. Combination of SAXS and DLS show in situ
      growth of nanoparticles in the individual droplets which consume the water
      insoluble product formed and undergo exchange coalescence with other droplets.
      The structural transition of the MDs is captured by observing the change in shape
      anisotropy, together with a detailed structural analysis of micelles in which the
      nanostructures grow as a function of time. Importantly, once the reaction is
      triggered, the nucleation of the droplets start instantly, and a very short
      period is noticed where MDs become cylindrical with approximate aspect ratio of
      4:1 in which nanostructures grow anisotropically and achieve an average critical
      size of 55 nm (elongated nanoparticles) signifying the existence of short
      nucleation-dominant particle growth period, beyond which a transition from
      elongated nanostructures to small rods is observed. The critical size for the
      elongated droplets is 80 nm in length and 18 nm in diameter, and these critical
      dimensions at the point of transition are a new finding about an asymmetric
      particle before the rods begin to start self-assembling. Once the shape of
      microemulsions turns cylindrical, the dynamical exchange with other
      microemulsions is very fast at both ends, resulting in the formation of nanorods
      of zinc oxalate and an increase in the aspect ratio of these rods. This growth
      process can be viewed as a morphologically templated nucleation process, and the
      droplets act as shaping vesicles for the formation of ZO nanorods. This study is
      significant since it attempts to correlate the size and shape of the reverse
      micellar (microemulsion) droplets with the newborn product nanoparticles inside
      the droplets and the subsequent growth of the nanoparticles within the droplets. 

PMID- 24673482
TI  - Extended storage of buffy coat platelet concentrates in plasma or a platelet
      additive solution.
AB  - BACKGROUND: Platelet (PLT) concentrates (PCs) prepared from whole blood in the
      United States are made using the PLT-rich plasma method. The PCs must be made
      within 8 hours of blood collection and stored for only 5 days. In Europe and
      Canada, PCs are made using the buffy coat (BC) method from whole blood held
      overnight at 22  degrees C and storage times may be up to 7 days. Our studies
      were designed to determine how long BC PLTs can be stored in plasma or Plasmalyte
      while meeting the FDA's poststorage viability criteria. STUDY DESIGN AND METHODS:
      Normal subjects donated whole blood that was stored at 22  degrees C for 22 +/- 2
      hours before preparation of BC PLTs. PLTs were stored for 5 to 8 days in either
      plasma or Plasmalyte concentrations of 65 or 80%. Radiolabeled autologous stored
      versus fresh PLT recoveries and survivals were assessed as well as poststorage in
      vitro assays. RESULTS: BC PLTs stored in either plasma or 65% Plasmalyte met FDA
      poststorage PLT recovery criteria for 7 days but survivals for only 6 days, while
      storage in 80% Plasmalyte gave very poor results. Both stored PLT recoveries and
      survivals correlated with the same donor's fresh results, but the correlation was
      much stronger between recoveries than survivals. In vitro measures of extent of
      shape change, morphology score, and pH best predicted poststorage PLT recoveries,
      while annexin V binding best predicted PLT survivals. CONCLUSION: BC PLTs stored
      in either plasma or 65% Plasmalyte meet FDA's poststorage viability criteria for
      6 days.

PMID- 24673484
TI  - Enhancement of binding affinity for amyloid aggregates by multivalent
      interactions of 99mTc-hydroxamamide complexes.
AB  - Deposition of amyloid aggregates has been regarded as an early stage of
      amyloidosis progression. An imaging probe that can image amyloid aggregates
      enables the early diagnosis of amyloidosis and contributes to the development of
      new medical therapies. High binding affinity for amyloid aggregates is essential
      to develop a useful molecular imaging probe. This article describes a new
      strategy to enhance the binding affinity of imaging agents targeting amyloid
      aggregates. We designed and synthesized novel (99m)Tc-hydroxamamide ((99m)Tc-Ham)
      complexes with a bivalent amyloid ligand and evaluated their binding affinity for
      amyloid aggregates by using beta-amyloid peptide (Abeta(1-42)) aggregates as a
      model. In vitro inhibition assay indicated that bivalent (99m)Tc-Ham complexes
      had much higher binding affinity for amyloid aggregates than monovalent
      complexes. In vitro autoradiography using Tg2576 mice showed the specific binding
      of bivalent (99m)Tc-Ham complexes to Abeta plaques in the mouse brain, as
      reflected in the results of the inhibition assay. The preliminary results suggest
      that a new molecular design based on bivalent (99m)Tc-Ham complexes may be
      reasonable to develop an imaging probe targeting amyloid aggregates. 

PMID- 24673485
TI  - Prospective associations between dietary patterns and cognitive performance
      during adolescence.
AB  - BACKGROUND: The aim of the study was to investigate prospective associations
      between dietary patterns and cognitive performance during adolescence. METHODS:
      Participants were sourced from the Western Australian Pregnancy Cohort (Raine)
      Study that includes 2868 children born between 1989 and 1992 in Perth, Western
      Australia. When the children were 17 years old (2006-2009), cognitive performance
      was assessed using a computerized cognitive battery of tests (CogState) that
      included six tasks. Using a food frequency questionnaire administered when the
      children were 14 years old (2003-2006), 'Healthy' and 'Western' dietary patterns
      were identified by factor analysis. Associations between dietary patterns at 14
      years of age and cognitive performance at 17 years of age were assessed
      prospectively using multivariate regression models. RESULTS: Dietary and
      cognitive performance data were available for 602 participants. Following
      adjustment for the 'Healthy' dietary pattern, total energy intake, maternal
      education, family income, father's presence in the family, family functioning and
      gender, we found that a longer reaction time in the detection task (beta = .016;
      95% CI: 0.004; 0.028; p = .009) and a higher number of total errors in the Groton
      Maze Learning Test - delayed recall task (beta = .060; 95% CI: 0.006; 0.114; p =
      .029) were significantly associated with higher scores on the 'Western' dietary
      pattern. The 'Western' dietary pattern was characterized by high intakes of take
      away food, red and processed meat, soft drink, fried and refined food. We also
      found that within the dietary patterns, high intake of fried potato, crisps and
      red meat had negative associations, while increased fruit and leafy green
      vegetable intake had positive associations with some aspects of cognitive
      performance. CONCLUSION: Higher dietary intake of the 'Western' dietary pattern
      at age 14 is associated with diminished cognitive performance 3 years later, at
      17 years.

PMID- 24673486
TI  - Erythropoietin attenuates oxidative stress and apoptosis in Schwann cells
      isolated from streptozotocin-induced diabetic rats.
AB  - OBJECTIVES: High glucose-evoked oxidative stress and apoptosis within Schwann
      cells (SCs) are mechanisms facilitating the procession of diabetic peripheral
      neuropathy (DPN). Although erythropoietin (EPO) was demonstrated to have
      neuroprotective effects in neurodegenerative diseases, the effects of EPO on
      glucose-evoked oxidative stress and apoptosis of SCs remain unknown. METHODS:
      Primary cultured SCs isolated from streptozotocin (STZ)-induced diabetic
      peripheral neuropathic rats and normal control rats were exposed to high or
      normal glucose condition with or without EPO incubation for 72 h. Cell viability,
      apoptotic rate, cellular reactive oxygen species (ROS) level, total glutathione
      (GSH) level, EPO mRNA and erythropoietin receptor (EPOR) mRNA levels were
      assayed. KEY FINDINGS: SCs from diabetic rats showed a lower cell viability and a
      higher apoptotic rate. High glucose culture condition elevated ROS level and
      diminished total GSH level of SCs. EPO improved cell viability and decreased cell
      apoptotic rate of SCs. EPO also elevated total GSH level and decreased
      intracellular ROS level. SCs from diabetic rats exhibited higher EPO mRNA and
      EPOR mRNA levels than SCs from normal control rats. CONCLUSIONS: The data of this
      study offered fresh viewpoints for interpreting the pathogenesis of DPN and novel
      pharmacological principles implicit in the therapeutic effect of EPO.

PMID- 24673487
TI  - CGRP and VIP levels as predictors of efficacy of Onabotulinumtoxin type A in
      chronic migraine.
AB  - BACKGROUND: Onabotulinumtoxin type A (onabotA) has shown efficacy in chronic
      migraine (CM). Its precise mechanism of action, however, is unknown. OBJECTIVE:
      To analyze a potential relationship between calcitonin gene-related peptide
      (CGRP) and vasoactive intestinal peptide (VIP) levels and response to onabotA in
      CM. METHODS: Adult patients with CM were recruited. Matched healthy subjects with
      no headache history served as controls. CGRP and VIP levels were determined in
      samples obtained from the right antecubital vein by ELISA outside of a migraine
      attack and having taken no symptomatic medication prior to treatment with
      onabotA. OnabotA was administered according to the PREEMPT protocol every 12
      weeks for at least two treatment cycles. A patient was considered as a moderate
      responder when both: (1) moderate-severe headache episodes were reduced by
      between 33 and 66%; (2) subjective benefit in a visual scale of 0-100 was
      recorded by the patient of between 33-66%. Patients were considered as excellent
      responders when both items improved >66%. Those without improvement of at least
      one-third in the two items were considered as nonresponders. RESULTS: We assessed
      plasma samples from 81 patients with CM and 33 healthy controls. CGRP and VIP
      levels were significantly increased in CM population vs controls. CGRP and, to a
      lesser degree, VIP levels were significantly increased in responders vs
      nonresponders. For CGRP, a threshold of 72 pg/mL positively correlated with 95%
      of nonresponders. The probability of being a responder to onabotA was 28 times
      higher in patients with a CGRP level above the threshold of 72 pg/mL. Even though
      the sensitivity for the calculated threshold for VIP was poor, the probability
      that CM patients with low CGRP levels will respond to onabotA was significantly
      higher in those patients with high VIP levels. CONCLUSIONS: Interictal CGRP and,
      to a lesser degree, VIP levels measured in peripheral blood are of great help in
      predicting response to onabotA.

PMID- 24673488
TI  - From parent to 'peer facilitator': a qualitative study of a peer-led parenting
      programme.
AB  - BACKGROUND: Peer-led interventions are increasingly common in community health
      settings. Although peer-led approaches have proven benefits for service users,
      relatively little is known about the process and outcomes of participation for
      peer leaders. This study investigated experiences of parents who had participated
      as 'peer facilitators' in Empowering Parents, Empowering Communities (EPEC), a
      peer-led programme designed to improve access to evidence-based parenting support
      in socially disadvantaged communities. METHOD: A qualitative cross-sectional
      design was used. Semi-structured interviews were conducted with 14 peer
      facilitators and scrutinized using thematic analysis. RESULTS: Peer facilitators
      developed their knowledge and skills through personal experience of receiving
      parenting support, participation in formal training and supervised practice,
      access to an intervention manual, and peer modelling. Peer facilitators described
      positive changes in their own families, confidence and social status.
      Transformative personal gains reinforced peer facilitators' role commitment and
      contributed to a cohesive 'family' identity among EPEC staff and service users.
      Peer facilitators' enthusiasm, openness and mutual identification with families
      were seen as critical to EPEC's effectiveness and sustainability. Peer
      facilitators also found the training emotionally and intellectually demanding.
      There were particular difficulties around logistical issues (e.g. finding
      convenient supervision times), managing psychosocial complexity and child
      safeguarding. CONCLUSIONS: The successful delivery and sustained implementation
      of peer-led interventions requires careful attention to the personal qualities
      and support of peer leaders. Based on the findings of this study, support should
      include training, access to intervention manuals, regular and responsive
      supervision, and logistical/administrative assistance. Further research is
      required to elaborate and extend these findings to other peer-led programmes.

PMID- 24673489
TI  - Activity of axitinib in patients with metastatic renal cell carcinoma previously
      treated with both vascular endothelial growth factor receptor tyrosine-kinase
      inhibitor and mammalian target of rapamycin inhibitor.

PMID- 24673490
TI  - Efficient magnetic recycling of covalently attached enzymes on carbon-coated
      metallic nanomagnets.
AB  - In the pursuit of robust and reusable biocatalysts for industrial synthetic
      chemistry, nanobiotechnology is currently taking a significant part. Recently,
      enzymes have been immobilized on different nanoscaffold supports. Carbon coated
      metallic nanoparticles were found to be a practically useful support for enzyme
      immobilization due to their large surface area, high magnetic saturation, and
      manipulatable surface chemistry. In this study carbon coated cobalt nanoparticles
      were chemically functionalized (diazonium chemistry), activated for
      bioconjugation (N,N-disuccinimidyl carbonate), and subsequently used in enzyme
      immobilization. Three enzymes, beta-glucosidase, alpha-chymotrypsin, and lipase B
      were successfully covalently immobilized on the magnetic nonsupport. The enzyme
      particle conjugates formed retained their activity and stability after
      immobilization and were efficiently recycled from milliliter to liter scales in
      short recycle times. 

PMID- 24673491
TI  - Computational and DNMR investigation of the isomerism and stereodynamics of the
      2,2'-binaphthalene-1,1'-diol scaffold.
AB  - The relative stabilities of three conformational isomers of 2,2'-binaphthalene
      1,1'-diol diisobutyrate and the energy barriers to rotation about the pivotal
      aryl-aryl bond and the two aryl-oxygen bonds were investigated by variable
      temperature NMR spectroscopy in conjunction with DFT computations. The
      experimental and calculated data were found to be in very good agreement and
      provide new insights into the dynamic stereochemistry of BINOL-derived tropos
      ligands. 

PMID- 24673492
TI  - Assessment of the effect of mesangial hypercellularity in childhood nephropathies
      to the clinical and laboratory findings.
AB  - AIM: To assess the relationship between mesangial hypercellularity in various
      childhood nephropathies and clinical and laboratory parameters. METHODS AND
      PATIENTS: The reports of the renal biopsies were evaluated retrospectively. The
      patients with diagnosis of IgA nephropathy (isolated and Henoch-Schonlein
      nephritis), IgM nephropathy, or isolated mesangial proliferative
      glomerulonephritis were included. Each nephropathy group was divided into two
      subgroups according to the severity of mesangial hypercellularity as mild and
      severe. The biochemical data and histopathological findings of the patients were
      recorded. RESULTS: When the groups were compared, it was found that the patients
      with IgA nephropathy had hematuria (p = 0.043) and the patients with IgM
      nephropathy had nephrotic syndrome more frequently than the other patients (p =
      0.01). No difference was detected between the groups regarding the severity of
      mesangial hypercellularity. On the other hand, when the groups were evaluated
      within themselves, no significant association was detected between the severity
      of mesangial hypercellularity and clinical and laboratory parameters. It was
      determined that the renal biopsy was performed earlier in patients with Henoch
      Schonlein nephritis compared to the other cases (p = 0.004). Compared to the
      isolated IgA nephropathy group, it was found that the number of cases with severe
      mesangial hypercellularity was higher and the level of proteinuria was more
      prominent in patients with Henoch-Schonlein nephritis. Additionally, when the
      patients with Henoch-Schonlein nephritis were evaluated, the degree of
      proteinuria was found to be higher in patients with severe mesangial
      hypercellularity compared to those of showing mild mesangial hypercellularity (p
      = 0.002). CONCLUSION: It was observed that there is no direct relation between
      the severity of mesangial hypercellularity and clinical and laboratory findings
      in various childhood nephropathies. However, when Henoch-Schonlein nephritis is
      compared with IgA nephropathy, it was found that the severity of mesangial
      hypercellularity was higher in cases with Henoch-Schonlein nephritis and the
      level of proteinuria was more prominent in those cases. However, no difference
      was detected in glomerular filtration rates and biochemical data with regard to
      the level of mesangial hypercellularity.

PMID- 24673493
TI  - T1 and T2 dual-mode MRI contrast agent for enhancing accuracy by engineered
      nanomaterials.
AB  - One of the holy grails in biomedical imaging technology is to achieve accurate
      imaging of biological targets. The development of sophisticated instrumentation
      and the use of contrast agents have improved the accuracy of biomedical imaging.
      However, the issue of false imaging remains a problem. Here, we developed a dual
      mode artifact filtering nanoparticle imaging agent (AFIA) that comprises a
      combination of paramagnetic and superparamagnetic nanomaterials. This AFIA has
      the ability to perform "AND logic gate" algorithm to eliminate false errors
      (artifacts) from the raw images to enhance accuracy of the MRI. We confirm the
      artifact filtering capability of AFIA in MRI phantoms and further demonstrate
      that artifact-free imaging of stem cell migration is possible in vivo. 

PMID- 24673494
TI  - A simple solubility tests for the discrimination of acrylic and modacrylic
      fibers.
AB  - In a crime scene investigation, single fibers play an important role as
      significant trace physical evidence. Acrylic fibers are frequently encountered in
      forensic analysis. Currently, acrylic and modacrylic are not discriminated
      clearly in Japan. Only results of FT-IR, some of acrylics were difficult to
      separate clearly to acrylic and modacrylic fibers. Solubility test is primitive
      but convenient useful method, and Japan Industrial Standards (JIS) recommends FT
      IR and solubility test to distinguish acrylic and modacrylic fibers. But
      recommended JIS dissolving test using 100% N,N-dimethylformamide (DMF) as a
      solvent, some acrylics could not be discriminated. In this report, we used DMF
      and ethanol (90:10, v/v) solvent. The JIS method could not discriminate 6
      acrylics in 60 acrylics; hence, DMF and ethanol (90:10, v/v) solvent
      discriminated 59 of the 60 fibers (43 acrylic and 16 modacrylic fibers) clearly,
      but only one modacrylic fiber incorrectly identified as acrylic.

PMID- 24673495
TI  - From whole brain to hospice: patterns of care in radiation oncology.
AB  - OBJECTIVES: The development of brain metastases is a common cause of morbidity
      and mortality in cancer patients. Limited life expectancy is well established
      once a patient requires whole-brain radiotherapy (WBRT). There is emerging
      evidence demonstrating the value of involving palliative care services alongside
      traditional treatments. However, data regarding the utilization of these services
      in patients requiring WBRT remain unexplored. METHODS: Patients with histologic
      or radiographic evidence of brain metastases treated with WBRT alone between July
      2010 and June 2012 were reviewed retrospectively. Patient demographics, the
      number of hospital admissions in the last 6 months of life, survival, and
      referrals to palliative care services were evaluated. RESULTS: Ninety-eight
      patients were diagnosed with brain metastases and treated with WBRT alone. The
      median overall survival following WBRT was 80 days. Twenty-eight of the patients
      presented to the emergency department >=2 times in the last 6 months of life.
      Sixty-eight percent of patients were referred to palliative care. Of those
      referrals, 57% were during an inpatient hospitalization. The median survival from
      palliative care referral to death was 27 days. CONCLUSIONS: Patients with brain
      metastasis requiring WBRT have a predictable dying trajectory. These patients are
      likely to have a high symptom burden and would benefit from palliative care.
      Timely palliative care referrals in this population remain inadequate and
      classically follow a hospital admission. Referrals continued to be late in the
      dying process and the recommendation for WBRT can be used as an independent
      marker for initiating end-of-life discussions and involving palliative care.

PMID- 24673496
TI  - Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes
      mellitus: a 12-week, randomized, double-blind, placebo-controlled, phase II
      study.
AB  - OBJECTIVES: Luseogliflozin is a selective sodium glucose cotransporter 2
      inhibitor under development for the treatment of type 2 diabetes mellitus (T2DM).
      This phase II study was conducted to confirm the efficacy and safety of
      luseogliflozin monotherapy at doses of up to 10 mg in Japanese patients with
      T2DM. PATIENTS AND METHODS: Patients with hemoglobin A1c (HbA1c) of 6.9-10.5% on
      diet therapy were randomized in a double-blind manner to treatment with 1, 2.5,
      5, or 10 mg luseogliflozin or placebo for 12 weeks (n = 56, 56, 54, 58, and 58,
      respectively). TRIAL REGISTRATION: Japan Pharmaceutical Information Center
      (identifier: Japic CTI-101191). MAIN OUTCOME MEASURES: The primary endpoint was
      the change in HbA1c from baseline to the end of treatment. Other endpoints
      included fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and body
      weight. Adverse events were recorded throughout the study. RESULTS: HbA1c
      decreased significantly at the end of treatment in the 1, 2.5, 5, and 10 mg
      luseogliflozin groups compared with placebo (-0.29, -0.39, -0.46, and -0.43%,
      respectively, versus +0.22%; all P < 0.001), as did FPG and PPG (all P < 0.001).
      Body weight also decreased significantly in all luseogliflozin groups compared
      with placebo (all P < 0.001). The incidence rates of adverse events (40.0-50.0%)
      were not significantly different among the five groups. The overall incidence of
      hypoglycemia was low. Limitations of this study include the short study duration
      and the relatively small sample size. CONCLUSIONS: In Japanese patients with
      T2DM, luseogliflozin was well tolerated, improved glycemic control, and reduced
      body weight over 12 weeks of treatment at all tested doses. Doses of >=2.5 mg
      achieved similar improvements in glycemic control.

PMID- 24673497
TI  - Efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's
      disease: results of a pooled analysis of two randomized, double-blind, placebo
      controlled trials in Japan.
AB  - BACKGROUND: With the increase in the aging population, there is a pressing need
      to provide effective treatment options for individuals with Alzheimer's disease
      (AD). Memantine is an N-methyl-D-aspartate receptor antagonist used to treat AD
      in > 80 countries worldwide, and studies in the USA and Europe have shown it to
      be effective in improving language deficits; however, there are currently no data
      on language improvements in Japanese patients treated with memantine. OBJECTIVES:
      To clarify the efficacy and safety of memantine in Japanese outpatients with
      moderate to severe AD, using a pooled analysis of two multicenter randomized
      placebo-controlled trials, a phase 2 dose-finding study and a phase 3 study.
      RESULTS: The final analysis comprised 633 patients (318 receiving memantine and
      315 placebo). Memantine produced better outcomes in terms of Severe Impairment
      Battery-Japanese version, Clinician's Interview-Based Impression of Change plus
      Japanese version, Behavioral Pathology in AD Rating Scale, and language scores,
      versus placebo. The overall incidence of adverse events and adverse reactions was
      similar between groups. CONCLUSION: In this pooled analysis of Japanese patients,
      memantine achieved better outcomes than placebo in terms of cognition, including
      attention, praxis, visuospatial ability and language, and behavioral and
      psychological symptoms, including activity disturbances and aggressiveness.

PMID- 24673498
TI  - The role of core needle biopsy in the preoperative diagnosis of follicular
      neoplasm of the thyroid.
AB  - Follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) can often be
      challenging to diagnose using core needle biopsy (CNB) specimens. We have
      developed the histologic criteria for the CNB diagnosis of FN and validated the
      usefulness of CNB. We retrospectively reviewed 184 CNBs and 224 FNACs diagnosed
      with FN/SFN. CNBs were histologically classified into four subgroups, based on
      the histologic features of follicular proliferation, fibrous capsulation, and
      surrounding parenchyma. Among 184 CNBs, 103 (55.9%) had previous FNAC results of
      non-diagnostic or indeterminate. Overall malignancy rates in FNAC (48%) and CNB
      (46%) were nearly identical (p > 0.05), and the neoplasm rate was higher in CNB
      (88%) than FNAC (74%) (p = 0.007). There was no significant difference in the
      malignancy rates among the four histologic subgroups. Among the 40 nodules with
      simultaneous CNB and FNAC, only nine had the FNAC diagnosis of FN/SFN, and others
      were non-diagnostic, benign, or atypia of undetermined significance. Overall, CNB
      improved specimen adequacy and achieved better sensitivity of the FN/SFN
      diagnosis in thyroid nodules that were inconclusive by FNAC. In the preoperative
      diagnosis of FN/SFN, CNB has no advantage over FNAC in predicting the likelihood
      of malignancy, but helps to reduce the need for repeat biopsy. 

PMID- 24673499
TI  - Offsetting the impacts of mining to achieve no net loss of native vegetation.
AB  - Offsets are a novel conservation tool, yet using them to achieve no net loss of
      biodiversity is challenging. This is especially true when using conservation
      offsets (i.e., protected areas) because achieving no net loss requires avoiding
      equivalent loss. Our objective was to determine if offsetting the impacts of
      mining achieves no net loss of native vegetation in Brazil's largest iron mining
      region. We used a land-use change model to simulate deforestation by mining to
      2020; developed a model to allocate conservation offsets to the landscape under 3
      scenarios (baseline, no new offsets; current practice, like-for-like [by
      vegetation type] conservation offsetting near the impact site; and threat
      scenario, like-for-like conservation offsetting of highly threatened vegetation);
      and simulated nonmining deforestation to 2020 for each scenario to quantify
      avoided deforestation achieved with offsets. Mines cleared 3570 ha of native
      vegetation by 2020. Under a 1:4 offset ratio, mining companies would be required
      to conserve >14,200 ha of native vegetation, doubling the current extent of
      protected areas in the region. Allocating offsets under current practice avoided
      deforestation equivalent to 3% of that caused by mining, whereas allocating under
      the threat scenario avoided 9%. Current practice failed to achieve no net loss
      because offsets did not conserve threatened vegetation. Explicit allocation of
      offsets to threatened vegetation also failed because the most threatened
      vegetation was widely dispersed across the landscape, making conservation
      logistically difficult. To achieve no net loss with conservation offsets requires
      information on regional deforestation trajectories and the distribution of
      threatened vegetation. However, in some regions achieving no net loss through
      conservation may be impossible. In these cases, other offsetting activities, such
      as revegetation, will be required.

PMID- 24673500
TI  - A novel allele, HLA-B*54:29, identified by sequence-based typing in a Chinese
      bone marrow donor.
AB  - HLA-B*54:29 allele differs from B*54:01:01 at nucleotide position 442 A>C in exon
      3. 

PMID- 24673501
TI  - Palladium-catalyzed oxidative annulation of acrylic acid and amide with alkynes:
      a practical route to synthesize alpha-pyrones and pyridones.
AB  - A range of internal alkynes smoothly underwent palladium-catalyzed oxidative
      annulations with acrylic acid and amide to afford alpha-pyrones and pyridones in
      good to excellent yields with high regioselectivity. The usage of O2 (1 atm) as a
      stoichiometric oxidant with H2O as the only byproduct under mild conditions makes
      this process more attractive and practical. 

PMID- 24673502
TI  - Dropouts in sublingual allergen immunotherapy trials - a systematic review.
AB  - Participant dropouts can reduce the power of allergen immunotherapy clinical
      trials. Evaluation of the dropout rate and reasons for dropout are important not
      only in the planning of clinical studies but are also relevant for adherence to
      immunotherapy in daily clinical practice. A systematic review was carried out in
      order to establish the overall dropout rate among published double-blind, placebo
      controlled randomized clinical trials of sublingual immunotherapy for respiratory
      allergic diseases. Dropouts were analysed in regards to allergen, formulation,
      treatment schedule, participant age, study size, number of centres and type of
      allergic disease. Relative dropout rates in placebo and active groups as well as
      reasons for dropout were also assessed. A total of 81 studies, comprising 9998
      patients, were included. Dropout rates in sublingual immunotherapy controlled
      studies do not appear to be a major problem with a composite dropout percentage
      of 14% (95% CI:11.9-16). Furthermore, they are not different for active compared
      to placebo-treated participants. This lends support to the positive clinical
      outcomes seen in meta-analyses of these trials. 

PMID- 24673503
TI  - Intravesical prostatic protrusion as a predictor of early urinary continence
      recovery after laparoscopic radical prostatectomy.
AB  - OBJECTIVES: To evaluate the significance of intravesical prostatic protrusion as
      a predictor of early urinary continence recovery after laparoscopic radical
      prostatectomy. METHODS: A total of 242 patients who underwent laparoscopic
      radical prostatectomy were included in the study. Data on incontinence status and
      the number of pads required per day for urinary incontinence were collected.
      Urinary continence was defined as no pad use or occasional security pad use.
      Intravesical prostatic protrusion was measured by the vertical distance from the
      tip of the protruding prostate to the base of the urinary bladder in the sagittal
      plane of preoperative magnetic resonance imaging. Continence at 1, 3, 6 and 12
      months postoperatively was assessed by dividing the patients into two groups
      based on the degree of intravesical prostatic protrusion. The correlation between
      preoperative factors and urinary continence after laparoscopic radical
      prostatectomy was examined. RESULTS: The urinary continence rates at
      postoperative month 1, 3, 6 and 12 were 19%, 50%, 79.8% and 92.1%, respectively.
      In the multivariate logistic analysis, intravesical prostatic protrusion was a
      significant independent predictive factor of early urinary continence at 1, 3, 6,
      9 and 12 months. Markedly improved urinary continence was observed in the non
      significant intravesical prostatic protrusion group (intravesical prostatic
      protrusion <5 mm) at all periods compared with the significant intravesical
      prostatic protrusion group (intravesical prostatic protrusion >=5 mm; P < 0.05).
      CONCLUSIONS: These findings suggest that the likelihood of postoperative urinary
      incontinence in patients undergoing laparoscopic radical prostatectomy is
      markedly higher in those with larger intravesical prostatic protrusion, and that
      intravesical prostatic protrusion is correlated with the duration of
      postoperative urinary incontinence.

PMID- 24673504
TI  - Impact of acellular hemoglobin-based oxygen carriers on brain apoptosis in rats.
AB  - BACKGROUND: Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under
      extensive consideration as oxygen therapeutics. Their effects on cellular
      mechanisms related to apoptosis are of particular interest, because the onset of
      proapoptotic pathways may give rise to tissue damage. STUDY DESIGN AND METHODS:
      The objective was to assess whether the properties of the Hb that replaces blood
      during an isovolemic hemodilution would modulate apoptotic-response mechanisms in
      rat brain and whether such signaling favors cytoprotection or damage. We exposed
      rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement
      with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen
      affinity], and alphaalphaHb [alphaalpha-cross-linked HBOC with low oxygen
      affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at
      2, 6, and 12 hours after ET; brain tissue was harvested and processed for
      analysis. RESULTS: In MP4OX animals, the number of neurons that overexpressed the
      hypoxia-inducible factor (HIF)-1alpha was higher than in alphaalphaHb,
      particularly at the early time points. In addition, MP4OX was associated with
      greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective
      factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl
      transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX <
      Hextend < alphaalphaHb. CONCLUSION: Even though both HBOCs showed increased
      levels of HIF-1alpha compared to shams or Hextend-treated animals, differences in
      signaling events resulted in very different outcomes for the two HBOCs.
      alphaalphaHb-treated brain tissue showed significant neuronal damage, measured as
      apoptosis. This was in stark contrast to the protection seen with MP4OX,
      apparently due to recruitment of Akt and neuronal specific HIF-1alpha pathways.

PMID- 24673505
TI  - Mothers' work-family conflict and enrichment: associations with parenting quality
      and couple relationship.
AB  - BACKGROUND: Employment participation of mothers of young children has steadily
      increased in developed nations. Combining work and family roles can create
      conflicts with family life, but can also bring enrichment. Work-family conflict
      and enrichment experienced by mothers may also impact children's home
      environments via parenting behaviour and the couple relationship, particularly in
      the early years of parenting when the care demands for young children is high.
      METHODS: In order to examine these associations, while adjusting for a wide range
      of known covariates of parenting and relationship quality, regression models
      using survey data from 2151 working mothers of 4- to 5-year-old children are
      reported. RESULTS/CONCLUSION: Results provided partial support for the predicted
      independent relationships between work-family conflict, enrichment and indicators
      of the quality of parenting and the couple relationship.

PMID- 24673506
TI  - Is that dog a pit bull? A cross-country comparison of perceptions of shelter
      workers regarding breed identification.
AB  - Bull breeds are commonly kept as companion animals, but the pit bull terrier is
      restricted by breed-specific legislation (BSL) in parts of the United States and
      throughout the United Kingdom. Shelter workers must decide which breed(s) a dog
      is. This decision may influence the dog's fate, particularly in places with BSL.
      In this study, shelter workers in the United States and United Kingdom were shown
      pictures of 20 dogs and were asked what breed each dog was, how they determined
      each dog's breed, whether each dog was a pit bull, and what they expected the
      fate of each dog to be. There was much variation in responses both between and
      within the United States and United Kingdom. UK participants frequently labeled
      dogs commonly considered by U.S. participants to be pit bulls as Staffordshire
      bull terriers. UK participants were more likely to say their shelters would
      euthanize dogs deemed to be pit bulls. Most participants noted using dogs'
      physical features to determine breed, and 41% affected by BSL indicated they
      would knowingly mislabel a dog of a restricted breed, presumably to increase the
      dog's adoption chances. 

PMID- 24673507
TI  - The effect of intrachain electrostatic repulsion on conformational disorder and
      dynamics of the Sic1 protein.
AB  - The yeast cyclin-dependent kinase inhibitor Sic1 is a disordered protein that,
      upon multisite phosphorylation, forms a dynamic complex with the Cdc4 subunit of
      an SCF ubiquitin ligase. To understand the multisite phosphorylation dependence
      of the Sic1:Cdc4 interaction, which ultimately leads to a sharp cell cycle
      transition, the conformational properties of the disordered Sic1 N-terminal
      targeting region were studied using single-molecule fluorescence spectroscopy.
      Multiple conformational populations with different sensitivities to charge
      screening were identified by performing experiments in nondenaturing salts and
      ionic denaturants. Both the end-to-end distance and the hydrodynamic radius
      decrease monotonically with increasing the salt concentration, and a rollover of
      the chain dimensions in high denaturant conditions is observed. The data were fit
      to the polyelectrolyte binding-screening model, yielding parameters such as the
      excluded volume of the uncharged chain and the binding constant to denaturant. An
      overall scaling factor of ~1.2 was needed for fitting the data, which implies
      that Sic1 cannot be approximated by a random Gaussian chain. Fluorescence
      correlation spectroscopy reveals Sic1 structure fluctuations occurring on both
      fast (10-100 ns) and slow (~10 ms) time scales, with the fast phase absent in low
      salt solutions. The results of this study provide direct evidence that long-range
      intrachain electrostatic repulsions are a significant factor for the
      conformational landscape of Sic1, and support the role of electrostatics in
      determining the overall shape and hydrodynamic properties of intrinsically
      disordered proteins. 

PMID- 24673508
TI  - Predicting neurocognitive and behavioural outcome after early brain insult.
AB  - AIMS: The aims of the study were to investigate (1) the impact of age at brain
      insult on functional outcome and (2) the influence of insult and environmental
      factors on cognitive and behavioural outcomes. METHOD: The study was a cross
      sectional, retrospective observational study, involving 138 children (76 males,
      62 females; mean age 13y 1mo, SD 1y 11mo, range 10-16y) with magnetic resonance
      imaging (MRI) evidence of focal brain insult sustained from the first trimester
      of pregnancy to adolescence. Children underwent MRI and intellectual, executive,
      behavioural, and social evaluation. Outcome predictors were insult (lesion
      location, laterality, and extent, history of seizures, age at insult) and
      environmental (social risk and family function) factors. RESULTS: Focal insult
      before the age of 3 years was associated with poorer outcomes than insult after
      the age of 3 years across all domains. For IQ outcomes, insult characteristics
      and seizures were highly predictive. For executive and behavioural domains,
      family function and social risk had the greatest impact. Earlier age at insult
      predicted poorer social competence. INTERPRETATION Focal brain insult before age
      3 years has devastating consequences for children's development. Findings suggest
      that greater emphasis should be placed on providing early intervention for
      children who sustain early focal brain insults.

PMID- 24673509
TI  - Comparison of depression, anxiety, quality of life, vitality and mental health
      between premenopausal and postmenopausal women.
AB  - OBJECTIVE: The purpose of this research was to investigate and compare the rates
      of depression, anxiety, quality of life, vitality and mental health between
      premenopausal and postmenopausal women. METHOD: The sample included 218 women
      selected randomly from the cultural center of Tehran in November and December
      2013 and was divided into two groups. The first group included 110 postmenopausal
      women (45-55 years old). One year had passed since their last monthly period and
      they had not used any hormones. The second group included 108 premenopausal women
      (35-45 years old) who had not yet experienced menopause. In order to assess data,
      three tests were used: the Zung Anxiety Self-Report scale, the Beck Depression
      Inventory and the Quality of Life questionnaire (SF-36). The gathered data were
      analyzed with the T-test for independent groups. RESULTS: The results indicated
      that all five hypotheses were confirmed. There were significant differences
      between the scores of anxiety, depression, quality of life, vitality and mental
      health between the two groups. CONCLUSION: Since menopausal women spend almost
      one-third of their long life in this situation, it can be useful to recognize the
      causes of these disorders in women and their influences on their families. We can
      also increase their motivation and self-efficacy in order to improve their
      quality of life.

PMID- 24673511
TI  - My first year as an oncologist.

PMID- 24673510
TI  - Retro-inverso isomer of Angiopep-2: a stable d-peptide ligand inspires brain
      targeted drug delivery.
AB  - The blood-brain barrier (BBB) prevents most drugs from reaching the site of
      central nervous system (CNS) diseases, intensively confining the therapeutic
      efficiency. Angiopep-2 (here termed (L)Angiopep), which is a 19-mer peptide
      derived from human Kunitz domain, can trigger transcytosis and traverse the BBB
      by recognizing low density lipoprotein-related protein 1 (LRP-1) expressed on the
      brain capillary endothelial cells. Various enzymes in the blood and the BBB,
      however, present multiple metabolic barriers to peptide-inspired brain-targeted
      drug delivery. Here we designed a retro-inverso isomer of (L)Angiopep, termed
      (D)Angiopep, to inspire brain-targeted drug delivery. Both (D)Angiopep and
      (L)Angiopep displayed high uptake capacity in LRP-1 overexpressed cells,
      including bEnd.3 and U87 cells. (D)Angiopep demonstrated lower uptake efficiency
      in both cell lines than did (L)Angiopep, suggestive of lower binding affinity to
      LRP-1 of the d-peptide. (D)Angiopep was resistant to proteolysis in fresh rat
      blood serum, while more than 85% of (L)Angiopep disappeared within 2 h.
      Endocytosed (D)Angiopep and (L)Angiopep were found to be colocalized with
      lysosomal compartments of bEnd.3 cells, indicating that susceptibility to
      proteolysis of (L)Angiopep in the BBB may further attenuate its transcytosis
      efficiency. In vivo, (D)Angiopep modified PEG-DSPE micelles displayed high
      distribution in normal brain and intracranial glioblastoma. Due to the expression
      of LRP-1 on the BBB and glioblastoma cells, proteolytically stable (D)Angiopep
      holds much potential for designing two-order brain tumor targeted delivery
      systems. 

PMID- 24673512
TI  - Clinical activity of everolimus in relapsed/refractory marginal zone B-cell
      lymphomas: results of a phase II study of the International Extranodal Lymphoma
      Study Group.
AB  - The International Extranodal Lymphoma Study Group coordinated a phase II trial to
      evaluate the activity and safety of everolimus in marginal zone lymphomas (MZLs).
      Thirty patients with relapsed/refractory MZLs received everolimus for six cycles
      or until dose-limiting toxicity or progression. Median age was 71 years (range,
      51-88 years). Twenty patients had extranodal, six splenic, four nodal MZL. Twenty
      four patients had stage III-IV. Median number of prior therapies was two (range 1
      5). Seventeen patients had early treatment discontinuation, in most cases due to
      toxicity. Median number of cycles was 4.5 (range, 1-16). Among the 24 assessable
      patients, the overall response rate (ORR) was 25% (95% confidence interval: 10
      47). Grade 3-4 adverse events were neutropenia and thrombocytopenia (17% of
      patients, each), infections (17%), mucositis and odontogenic infections (13%) and
      lung toxicity (3%). The median response duration was 6.8 months (range, 1.4
      11.1+). After a median follow-up of 14.5 months, five deaths were reported: four
      deaths were due to lymphoma, one was due to toxicity. In an intent-to-treat
      analysis, the projected median progression-free survival was 14 months. The
      moderate antitumour activity of everolimus in relapsed/refractory MZLs and the
      observed toxicity limit its therapeutical applicability in these indolent
      entities. Lower doses of the drug and, perhaps, different strategies including
      combination with additional agents need to be explored.

PMID- 24673513
TI  - Randomized, double-blind, placebo-controlled, multiple-dose study of the safety,
      tolerability and pharmacokinetics of benvitimod, a candidate drug for the
      treatment of psoriasis.
AB  - WHAT IS KNOWN AND OBJECTIVE: Benvitimod is a newly synthesized non-steroidal
      small molecule, aimed at the treatment for psoriasis. Several trials have
      demonstrated that benvitimod improves plaque psoriasis. However, its maximum
      tolerated dose and pharmacokinetic characteristics have not been reported on. The
      goals of this study were to evaluate the safety, tolerability and
      pharmacokinetics of benvitimod after topical administration in healthy subjects.
      METHODS: This phase I trial in healthy subjects was designed as a randomized,
      double-blind, placebo-controlled, ascending-dose study. After screening and
      randomization, 56 volunteers received benvitimod (0.5-2.0%) or placebo cream once
      or twice daily. Doses were escalated from 5 to 30 mg daily in six cohorts. Safety
      and tolerability were appraised by monitoring adverse events and laboratory
      parameters. Benvitimod concentrations were measured using liquid chromatography
      tandem-mass spectrometry. RESULTS AND DISCUSSION: Exposure to benvitimod did not
      result in electrocardiographic or clinical laboratory changes. Doses up to 30 mg
      were well tolerated. All adverse events were mild. Adverse effects at the
      application site were observed in subjects randomized to benvitimod 5 mg q.d and
      b.i.d, but there were no observable dose effects in the dose-range evaluated.
      Benvitimod was detected in fewer than 5% of the plasma samples. WHAT IS NEW AND
      CONCLUSIONS: Benvitimod cream, at single doses of up to 30 mg, is well tolerated
      by healthy subjects. Following topical application, systemic absorption was
      negligible.

PMID- 24673514
TI  - "Teeth are always in style": but increasingly, not for all.

PMID- 24673516
TI  - Diclofenac approval as a threat to Spanish vultures.

PMID- 24673517
TI  - The Ipswich Touch Test: a simple and novel method to screen patients with
      diabetes at home for increased risk of foot ulceration.
AB  - AIMS: The Ipswich Touch Test is a novel method to detect subjects with diabetes
      with loss of foot sensation and is simple, safe, quick, and easy to perform and
      teach. This study determines whether it can be used by relatives and/or carers to
      detect reduced foot sensation in the setting of the patient's home. METHODS: The
      test involves lightly and briefly (1-2 s) touching the tips of the first, third
      and fifth toes of both feet with the index finger. Reduced foot sensation was
      defined as >= 2 insensate areas. Patients due to attend clinic over a 4-week
      period were invited by post. The invitation contained detailed instructions and a
      sheet for recording the results. The findings were compared with those obtained
      in clinic using the 10-g monofilament at the same six sites. RESULTS: Of 331
      patients (174 males), 25.1% (n = 83) had >= 2 insensate areas to 10-g
      monofilament testing. Compared with this, the Ipswich Touch Test at home had a
      sensitivity of 78.3% and a specificity of 93.9%. The predictive values of
      detecting 'at-risk' feet were positive at 81.2% and negative at 92.8%. The
      likelihood ratios were positive at 12.9 and negative at 0.23. CONCLUSIONS: With
      clearly written instructions, this simple test can be used by non-professionals
      to accurately assess for loss of protective sensation. We believe that the
      Ipswich Touch Test may also be a useful educational adjunct to improve awareness
      of diabetes foot disease in patients and relatives alike and empower them to seek
      appropriate care if sensation was found to be abnormal.

PMID- 24673518
TI  - Genomic full-length sequence of two HLA-A alleles, A*01:01:01:01 and A*01:03,
      identified by cloning and sequencing.
AB  - Genomic full-length sequences of HLA-A*01:01:01:01 and A*01:03, were identified
      by cloning and sequencing from two Chinese donors. 

PMID- 24673519
TI  - Molecular mechanisms involved in the cytotoxicity induced by coumarins from
      Calophyllum brasiliense in K562 leukaemia cells.
AB  - OBJECTIVES: The aim of this study was to determine the cellular and molecular
      mechanisms of cell death induced by mammea A/BA and A/BB (3 : 1) on K562 cells.
      METHODS: These compounds were isolated from Calophyllum brasiliense and its
      cytotoxicity was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Cell death was evaluated by Terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and
      immunocytofluorescence of active caspase-3. Genotoxicity was tested using comet
      assay. Lastly, a chemoinformatic analysis was performed with Osiris
      Molinspiration software. KEY FINDINGS: The mixture of mammea A/BA and A/BB (3 :
      1) showed cytotoxic activity against K562 cells (IC50 = 43.5 MUm). TUNEL positive
      cells and active caspase-3 were detected after treatment. Genotoxicity of mammea
      A/BA and A/BB on K562 was detected since first hour of treatment. Additionally,
      mammea A/BA and A/BB were found to be in compliance with Lipinski 'rule of 5'
      suggesting that they possess strong potential of druglikeness. CONCLUSIONS: The
      overall results confirm and extend the knowledge about coumarins as an important
      resource of antitumor drugs, and indicate that these compounds could be used in
      further preclinical studies against leukaemia.

PMID- 24673520
TI  - Chemoselective palladium-catalyzed cyanation of alkenyl halides.
AB  - A palladium-catalyzed cyanation of alkenyl halides using acetone cyanohydrin is
      described. A number of structurally diverse alkenylic nitrile containing
      compounds was prepared in one step under optimized conditions. The reaction
      proved to be efficient, chemoselective, easy to perform, and tolerant of a number
      of functional groups. 

PMID- 24673522
TI  - Role of high mobility group box 1 and its signaling pathways in renal diseases.
AB  - The high mobility group box 1 (HMGB1) protein, a member of the high mobility
      group nuclear protein family and an endogenous ligand for TLR2/4 and RAGE
      (receptor for advanced glycation end products), is one of the most evolutionarily
      conserved proteins and it has recently emerged as an extracellular signaling
      factor with key roles in cell differentiation, proliferation and disease
      pathogenesis. The present data indicate that HMGB1 is one of most important
      proinflammatory cytokines, and plays an important role in renal diseases. The
      literatures were searched extensively and this review was performed to sum up the
      role of HMGB1 in renal diseases.

PMID- 24673521
TI  - Adolescent deviant peer clustering as an amplifying mechanism underlying the
      progression from early substance use to late adolescent dependence.
AB  - BACKGROUND: Early substance use co-occurs with youths' self-organization into
      deviant peer groups in which substance use is central to social interaction. We
      hypothesized that the social dynamics of deviant peer groups amplify the risk of
      progressing from early use to later dependence, and that this influence occurs
      over and above escalations in use that typically accompany early substance use
      and membership in deviant groups. METHODS: Our study used a longitudinal,
      multimethod dataset consisting of 998 adolescents and their families.
      Participants were recruited from middle schools in a large metropolitan area in
      the Pacific Northwest. The sample was 47.3% female and ethnically diverse (42.3%
      European American, 29.1% African American, and 28.6% other, including biracial).
      We examined deviant peer clustering as a mediator between early substance use and
      later dependence, controlling for proximal levels of use, SES, early antisocial
      behavior, and parental monitoring. Tobacco, alcohol, and marijuana use were
      assessed at ages 12, 13, and 16-17. Past-year nicotine, alcohol, and marijuana
      dependence (DSM-IV) was assessed at age 19. Youth and parent reports and
      observational data were used to assess deviant peer clustering at age 16-17, and
      youth reported on antisocial behavior and parental monitoring at ages 12 and 13.
      RESULTS: Early substance use predicted increased likelihood of dependence on
      tobacco, alcohol, and marijuana by late adolescence. Deviant peer affiliation
      mediated these links, even when accounting for proximal levels of substance use.
      CONCLUSIONS: Early substance use not only promotes escalations in use across
      adolescence but also provides entry into a deviant social context that
      contributes to increased risk of dependence. Our results emphasize the importance
      of identifying and intervening in early substance use before it becomes an
      organizing factor in friendship selection and interaction. Deviant peer clusters
      are clearly an important avenue for intervention when seeking to interrupt the
      progression to substance dependence.

PMID- 24673523
TI  - Differential effects of adiponectin in osteoblast-like cells.
AB  - The skeleton should maintain an adequate volume, vigour and strength to carry out
      the role for which it is designed: to hold the whole soft tissue mass that shapes
      the body and to protect the vital organs. To fulfil this task a satisfactory food
      intake is required and regulators that are released in the feeding and fasting
      states, among other signals indicate how much soft mass needs to be built up.
      Those signals include the secretion of adipocytokines which could represent a
      relevant link between soft mass (adipose tissue) and skeleton. We studied the
      presence of adiponectin receptors (AdipoR1, AdipoR2) and its direct effects in
      osteosarcoma cell line Saos-2. The results indicated that adiponectin receptors
      were present in the osteoblastic cells with a higher expression of AdipoR1. Human
      recombinant globular adiponectin was able to increase viability levels and
      decrease cytotoxicity rates in cell cultures. Also, adiponectin significantly
      inhibited alkaline phosphatase activity in supernatants. Osteoprotegerin mRNA
      expression was significantly reduced after 72 h treatment. The FOS induction was
      studied and the results exhibited a significant increase caused by adiponectin.
      In conclusion, all these observations suggest that adiponectin influences bone
      metabolism decreasing the levels of bone formation. Regulators of adiponectin or
      its receptors could be circulating to modulate the activities of this peptide.

PMID- 24673524
TI  - IGF-1 induces iNOS expression via the p38 MAPK signal pathway in the anti
      apoptotic process in pulmonary artery smooth muscle cells during PAH.
AB  - Apoptosis and cell proliferation are two important cellular processes that
      determine the accumulation of pulmonary artery smooth muscle cells (PASMC) during
      pulmonary arterial hypertension (PAH). Insulin-like growth factor 1 (IGF-1) is an
      endocrine and autocrine/paracrine growth factor that circulates at high levels in
      the plasma and is expressed in most cell types. IGF-1 has major effects on
      development, cell growth and differentiation, also tissue repair. Inducible
      nitric oxide synthase (iNOS) has been shown to serve many vasoprotective roles in
      vascular smooth muscle cells (VSMCs) including inhibition of VSMC proliferation
      and migration and stimulation of endothelial cell growth. In this study, we
      investigated the involvement of iNOS in the process of IGF-1-induced inhibition
      of PASMC apoptosis. We also examined the role of p38 mitogen-activated protein
      kinase (MAPK) in the IGF-1-induced iNOS activation. Our results show that
      exogenous IGF-1 induced the up-regulation of iNOS in PASMC. Immunofluorescence of
      IGF-1 and iNOS showed a decreased immunostaining of both IGF-1 and iNOS in the
      cytoplasm and the perinucleus under serum deprivation condition. iNOS inhibition
      in PASMC in vitro markedly induced IGF-1-mediated anti-apoptosis as assessed by
      the cell viability measurement, Western blot, mitochondrial potential analysis
      and nuclear morphology determination. A p38 MAPK inhibitor blocked all the
      effects of IGF-1 on iNOS. Our findings suggest that IGF-1 inhibits cells
      apoptosis in PASMC by activating the p38 MAPK-iNOS transduction pathway. This
      mechanism may contribute to the accumulation of PASMC in early human PAH.

PMID- 24673525
TI  - Clinicopathological characteristics of PIK3CA and HBx mutations in Korean
      patients with hepatocellular carcinomas.
AB  - Hepatocellular carcinoma (HCC) is the fourth most common form of cancer in the
      Korean population, caused primarily by infection with either the Hepatitis B or C
      virus. Progression of this disease is frequently associated with mutations in
      either phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) or hepatitis B virus
      X (HBx) gene. Previous studies have examined the frequency of PIK3CA mutations in
      HCC, although the clinical significance of these mutations has not been studied
      in a Korean population. In addition, HBx appears to play a key role in modulating
      a wide range of cellular functions, leading to HCC. In this study, we examined
      microdissected tumor samples from 50 HCC patients who underwent hepatectomy at
      Keimyung University Dongsan Medical Center. These patients were screened for
      mutations in PIK3CA and HBx to identify the clinical outcomes associated with
      these mutations. Exons 9 and 20 of PIK3CA and the entirety of HBx were screened
      for mutations by polymerase chain reaction and direct DNA sequencing. PIK3CA
      mutations were detected in 7 of 50 patients (14%). Among the 42 patients who were
      seropositive for hepatitis B, 17 (40.5%) had HBx mutations and 4 (9.52%) had
      mutations in PIK3CA. PIK3CA mutations were strongly correlated with tumor size.
      Patients harboring HBx mutations exhibited a longer time to recurrence; this
      difference was statistically significant not only in comparison with the PIK3CA
      mutation but also compared with those without any mutations. This result suggests
      a role for PIK3CA and HBx mutations as prognostic markers in HCC. 

PMID- 24673526
TI  - Editorial comment to intravesical prostatic protrusion as a predictor of early
      urinary continence recovery after laparoscopic radical prostatectomy.

PMID- 24673527
TI  - Using a single electrospun polymer nanofiber to enhance carrier mobility in
      organic field-effect transistors toward nonvolatile memory.
AB  - In this work, a single electrospun polymer nanofiber was employed as an
      additional dielectric in organic field-effect transistors where the active
      channel was a layer of pentacene. A high field-effect mobility (>1.50
      cm(2)/(V.s)) and a high ON/OFF current ratio (>10(6)) could be achieved by the
      use of such a nanofiber. Probing by electron microscopy, atomic force microscopy,
      and scattering techniques, we found that the geometry of the fiber is key to
      induce a pentacene morphology with large and oriented grains that facilitates the
      charge transport in pentacene layer along the fiber. The feasibility of
      nonvolatile memory based on this new type of transistor has been explored and the
      devices showed a fairly high memory window and reliable memory characteristics.
      In addition to pure polymers, the effects of composite nanofibers with dispersed
      [6,6]-phenyl-C61-butyric acid methyl ester were also investigated, and the
      electrical properties and memory characteristics of the transistors were found to
      be further improved. This study highlights the importance of dielectric geometry
      to pentacene morphology that is decisive for the performances of organic field
      effect transistors. 

PMID- 24673528
TI  - Chronic urticaria and coagulation: pathophysiological and clinical aspects.
AB  - Chronic urticaria (CU) is a widespread skin disease, characterized by the
      recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune
      mechanisms, coagulation factors, in particular tissue factor and thrombin, might
      also participate in the disease pathophysiology. Tissue factor expressed by
      eosinophils can induce activation of blood coagulation generating thrombin which
      in turn can increase vascular permeability both directly, acting on endothelial
      cells, and indirectly, inducing degranulation of mast cells with release of
      histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation
      product, generated following activation of the coagulation cascade and
      fibrinolysis, has been found to be increased during urticaria exacerbations;
      moreover, it has been proposed as a biomarker of severity and resistance to H1
      antihistamines in CU patients. The possible role of coagulation in CU is also
      supported by case reports, case series and a small controlled study showing the
      efficacy of anticoagulant therapy in this disease. The purpose of this review was
      to summarize the available data on the possible contribution of coagulation to
      the pathophysiology of CU focusing on clinical aspects and possible future
      therapeutic developments.

PMID- 24673529
TI  - Cysteine scanning mutagenesis of transmembrane domain 10 in organic anion
      transporting polypeptide 1B1.
AB  - Organic anion transporting polypeptide (OATP) 1B1 is an important drug
      transporter expressed in human hepatocytes. Previous studies have indicated that
      transmembrane (TM) domain 2, 6, 8, 9, and in particular 10 might be part of the
      substrate binding site/translocation pathway. To explore which amino acids in
      TM10 are important for substrate transport, we mutated 34 amino acids
      individually to cysteines, expressed them in HEK293 cells, and determined their
      surface expression. Transport activity of the two model substrates estrone-3
      sulfate and estradiol-17beta-glucuronide as well as of the drug substrate
      valsartan for selected mutants was measured. Except for F534C and F537C, all
      mutants were expressed at the plasma membrane of HEK293 cells. Mutants Q541C and
      A549C did not transport estradiol-17beta-glucuronide and showed negligible
      estrone-3-sulfate transport. However, A549C showed normal valsartan transport.
      Pretreatment with the anionic and cell impermeable sodium (2
      sulfonatoethyl)methanethiosulfonate (MTSES) affected the transport of each
      substrate differently. Pretreatment of L545C abolished estrone-3-sulfate uptake
      almost completely, while it stimulated estradiol-17beta-glucuronide uptake.
      Further analyses revealed that mutant L545C in the absence of MTSES showed
      biphasic kinetics for estrone-3-sulfate that was converted to monophasic kinetics
      with a decreased apparent affinity, explaining the previously seen inhibition. In
      contrast, the apparent affinity for estradiol-17beta-glucuronide was not changed
      by MTSES treatment, but the Vmax value was increased about 4-fold, explaining the
      previously seen stimulation. Maleimide labeling of L545C was affected by
      preincubation with estrone-3-sulfate but not with estradiol-17beta-glucuronide.
      These results strongly suggest that L545C is part of the estrone-3-sulfate
      binding site/translocation pathway but is not directly involved in
      binding/translocation of estradiol-17beta-glucuronide. 

PMID- 24673533
TI  - Managing moderate and severe pain in mountain rescue.
AB  - AIMS: We aimed to describe evidence-based options for prehospital analgesia, and
      to offer practical advice to physicians and nonphysicians working in mountain
      rescue. METHODS: A literature search was performed; the results and
      recommendations were discussed among the authors. Four authors considered a
      scenario. The final article was discussed and approved by the International
      Commission for Mountain Emergency Medicine (ICAR MEDCOM) in October 2013. RESULTS
      AND RECOMMENDATIONS: Many health care providers fail to recognize, assess, and
      treat pain adequately. Assessment scales and treatment protocols should be
      implemented in mountain rescue services to encourage better management of pain.
      Specific training in assessing and managing pain is essential for all mountain
      rescuers. Persons administrating analgesics should receive appropriate detailed
      training. There is no ideal analgesic that will accomplish all that is expected
      in every situation. A range of drugs and delivery methods will be needed. Thus,
      an 'analgesic module' reflecting its users and the environment should be
      developed. The number of drugs carried should be reduced to a minimum by careful
      selection and, where possible, utilizing drugs with multiple delivery options. A
      strong opioid is recommended as the core drug for managing moderate or severe
      pain; a multimodal approach may provide additional benefits.

PMID- 24673535
TI  - The effect of climbing Mount Everest on spleen contraction and increase in
      hemoglobin concentration during breath holding and exercise.
AB  - Release of stored red blood cells resulting from spleen contraction improves
      human performance in various hypoxic situations. This study determined spleen
      volume resulting from two contraction-evoking stimuli: breath holding and
      exercise before and after altitude acclimatization during a Mount Everest ascent
      (8848 m). Eight climbers performed the following protocol before and after the
      climb: 5 min ambient air respiration at 1370 m during rest, 20 min oxygen
      respiration, 20 min ambient air respiration at 1370 m, three maximal-effort
      breath holds spaced by 2 min, 10 min ambient air respiration, 5 min of cycling at
      100 W, and finally 10 min ambient air respiration. We measured spleen volume by
      ultrasound and capillary hemoglobin (HB) concentration after each exposure, and
      heart rate (HR) and arterial oxygen saturation (Sao2) continuously. Mean (SD)
      baseline spleen volume was unchanged at 213 (101) mL before and 206 (52) mL after
      the climb. Before the climb, spleen volume was reduced to 184 (83) mL after three
      breath holds, and after the climb three breath holds resulted in a spleen volume
      of 132 (26) mL (p=0.032). After exercise, the preclimb spleen volume was 186 (89)
      mL vs. 112 (389) mL) after the climb (p=0.003). Breath hold duration and
      cardiovascular responses were unchanged after the climb. We concluded that spleen
      contraction may be enhanced by altitude acclimatization, probably reflecting both
      the acclimatization to chronic hypoxic exposure and acute hypoxia during physical
      work.

PMID- 24673534
TI  - Meta-analysis of clinical efficacy of sildenafil, a phosphodiesterase type-5
      inhibitor on high altitude hypoxia and its complications.
AB  - OBJECTIVE: High altitude illness can be life-threatening if left untreated. Acute
      mountain sickness and high altitude pulmonary hypertension are two syndromes of
      high altitude illness. Recent clinical studies showed the beneficial effects of
      phosphodiesterase type 5 (PDE-5) inhibitors on the treatment of pulmonary
      hypertension. In this report, we performed a meta-analysis to evaluate the
      clinical efficacy of PDE-5 inhibitors on high altitude hypoxia and its
      complications. METHODS: Randomized controlled trials evaluating the efficacy of
      PDE-5 inhibitor in the setting of high altitude were identified by searching
      Cochrane Central Register of Controlled Trials (September 2013), PubMed (from
      1990 to September 2013), and EMBASE (from 1990 to September 2013). Extracted
      outcomes from selected studies for meta-analysis included arterial oxygen
      saturation, pulmonary artery systolic pressure, heart rate, and Lake Louise
      Consensus AMS symptom score. Weighted mean differences with 95% confidence
      intervals were presented for the continuous outcomes. RESULTS: Five clinical
      trials that met the selection criteria were identified for the meta-analysis. All
      of these studies used sildenafil as the PDE-5 inhibitor. A total of 60 subjects
      received sildenafil, and 72 subjects were given placebo. In accordance with
      previous report, short-term treatment with sildenafil (1-2 days) significantly
      reduced pulmonary artery systolic pressure at rest (MD -4.53; 95% CI -6.72, 
      2.34; p<0.0001). However, treatment with sildenafil (1-2 days) did not improve
      oxygen saturation after exposure to high altitude (MD 0.07; 95% CI -1.26, 1.41;
      p=0.91). Moreover, no significant difference was observed in heart rate between
      sildenafil and placebo-treated group (MD 6.95; 95% CI -3.53, 17.43; p=0.19). AMS
      score did not improve after treatment at different time points. CONCLUSION: Short
      term treatment with sildenafil can attenuate the altitude-induced high pulmonary
      systolic arterial pressure, but has no significant beneficial effects on arterial
      oxygen saturation, heart rate, and acute mountain sickness.

PMID- 24673536
TI  - Late hyperbaric oxygen treatment of cilioretinal artery occlusion with
      nonischemic central retinal vein occlusion secondary to high altitude.
AB  - AIM: To report a case of cilioretinal artery occlusion (CRAO) with central
      retinal vein occlusion (CRVO) after a journey to high altitude region and the use
      of late period hyperbaric oxygen (HBO) therapy successfully. CASE REPORT: A
      previously healthy 48-year-old lowlander woman was admitted to our department for
      sudden blurred vision in her right eye started at 2 weeks prior to examination.
      The patient had a history of 1-month exposure to high altitude that finished a
      day before the onset of her complaints. The best corrected visual acuity (BCVA)
      was 10/20 in the right eye (RE) and 10/10 in the left eye. Fundus examination of
      the RE revealed whitening of the retina along the distribution of cilioretinal
      artery, sparing fovea, flame-shaped hemorrhages, and roth spots with minimally
      dilated and tortuous retinal veins. Visual field analysis revealed centrocecal
      scotoma. The patient was treated by a daily session of 2 h of HBO at 2.5
      atmosphere absolute for 11 days. BCVA rised to a level of 20/20 for the RE and
      the scotomas were disappeared immediately after using of the HBO treatment.
      CONCLUSION: CRVO related CRAO should be regarded as a rare complication of
      exposure to high altitude and HBO seems to be the treatment of choice of high
      altitude related co-occurence of CRVO and CRAO in the late period.

PMID- 24673537
TI  - Report of proceedings of BMRES Altitude Medicine Conference November 22, 2013 at
      the Birmingham Medical Institute, Birmingham, United Kingdom.

PMID- 24673538
TI  - Nepalese mountain rescue development project.

PMID- 24673539
TI  - Portable hyperbaric chamber and management of hypothermia and frostbite: an
      evident utilization.

PMID- 24673541
TI  - The real superdonors.
AB  - Before frequency and age limits were established for blood donations, certain
      individuals were exceptional in the frequency and the number of blood donations
      over their life. We call them "superdonors" and describe their common
      characteristics through some examples. The physiologic characteristics allowing
      these individuals to give blood several hundred times without developing an
      anemia are unknown. 

PMID- 24673540
TI  - (18)F-FDG microPET imaging differentiates between septic and aseptic wound
      healing after orthopedic implant placement: a longitudinal study of an implant
      osteomyelitis in the rabbit tibia.
AB  - BACKGROUND AND PURPOSE: (18)F-FDG PET is a widely used tool for molecular imaging
      of oncological, cardiovascular, and neurological disorders. We evaluated (18)F
      FDG microPET as an implant osteomyelitis imaging tool using a Staphylococcus
      aureus-induced peroperative implant infection in rabbits. METHODS: Intramedullary
      titanium nails were implanted in contaminated and uncontaminated (control)
      proximal right tibiae of rabbits. Tibiae were quantitatively assessed with
      microPET for (18)F-FDG uptake before and sequentially at 1, 3, and 6 weeks after
      surgery. Tracer uptake was assessed in soft tissue and bone in both treatment
      groups with an additional comparison between the operated and unoperated limb.
      MicroPET analysis was combined with radiographic assessment and complementary
      histology of the tibiae. RESULTS: At the first postoperative week, the (18)F-FDG
      uptake in the contaminated implant group was significantly higher than the
      preoperative measurement, without a significant difference between the
      contaminated and uncontaminated tibiae. From the third postoperative week onward,
      (18)F-FDG uptake allowed discrimination between osteomyelitis and postoperative
      aseptic bone healing, as well as quantification of the infection at distinct
      locations around the implant. INTERPRETATION: (18)F-FDG-based microPET imaging
      allows differentiation between deep infection and undisturbed wound healing after
      implantation of a titanium intramedullary nail in this rabbit model. Furthermore,
      our results indicate that (18)F-FDG PET may provide a tool in human clinical
      diagnostics and for the evaluation of antimicrobial strategies in animal models
      of orthopedic implant infection.

PMID- 24673542
TI  - Brentuximab vedotin in heavily treated Hodgkin and anaplastic large-cell
      lymphoma, a single centre study on 45 patients.

PMID- 24673543
TI  - Estimating climate resilience for conservation across geophysical settings.
AB  - Conservationists need methods to conserve biological diversity while allowing
      species and communities to rearrange in response to a changing climate. We
      developed and tested such a method for northeastern North America that we based
      on physical features associated with ecological diversity and site resilience to
      climate change. We comprehensively mapped 30 distinct geophysical settings based
      on geology and elevation. Within each geophysical setting, we identified sites
      that were both connected by natural cover and that had relatively more
      microclimates indicated by diverse topography and elevation gradients. We did
      this by scoring every 405 ha hexagon in the region for these two characteristics
      and selecting those that scored >SD 0.5 above the mean combined score for each
      setting. We hypothesized that these high-scoring sites had the greatest
      resilience to climate change, and we compared them with sites selected by The
      Nature Conservancy for their high-quality rare species populations and natural
      community occurrences. High-scoring sites captured significantly more of the
      biodiversity sites than expected by chance (p < 0.0001): 75% of the 414 target
      species, 49% of the 4592 target species locations, and 53% of the 2170 target
      community locations. Calcareous bedrock, coarse sand, and fine silt settings
      scored markedly lower for estimated resilience and had low levels of permanent
      land protection (average 7%). Because our method identifies-for every geophysical
      setting-sites that are the most likely to retain species and functions longer
      under a changing climate, it reveals natural strongholds for future conservation
      that would also capture substantial existing biodiversity and correct the bias in
      current secured lands. 

PMID- 24673544
TI  - Do patients with advanced cancer and unmet palliative care needs have an interest
      in receiving palliative care services?
AB  - BACKGROUND: It is not known whether unmet palliative care needs are associated
      with an interest in palliative care services among patients with advanced cancer
      receiving ongoing oncology care. OBJECTIVE: To assess the association between
      unmet palliative care needs and patient interest in subspecialty palliative care
      services. DESIGN: Cross-sectional telephone survey. SUBJECTS AND SETTING: One
      hundred sixty-nine patients with advanced cancer receiving care from 20
      oncologists at two academic cancer centers. MEASUREMENTS: Surveys assessed
      palliative care needs in six domains. Patients were read a description of
      palliative care and then asked three questions about their current interest in
      subspecialty palliative care services (perceived need, likelihood of requesting,
      willingness to see if their oncologist recommended; all outcomes on 0-10 Likert
      scale). RESULTS: The vast majority of patients described unmet palliative care
      needs, most commonly related to psychological/emotional distress (62%) and
      symptoms (62%). In fully adjusted models accounting for clustering by oncologist,
      unmet needs in these domains were associated with a higher perceived need for
      subspecialty palliative care services (psychological/emotional needs odds ratio
      [OR] 1.30; 95% confidence interval [CI] 1.06-1.58; p=0.01; symptom needs OR 1.27;
      95% CI 1.01-1.60; p=0.04). There was no significant association between unmet
      needs and likelihood of requesting palliative care services. Willingness to see
      palliative care if oncologist recommended was high (mean 8.6/10, standard
      deviation [SD] 2). CONCLUSION: Patients with advanced cancer and unmet symptom
      and psychological/emotional needs perceive a high need for subspecialty
      palliative care services but may not request them. Efforts to increase
      appropriate use of subspecialty palliative care for cancer may require oncologist
      initiated referrals.

PMID- 24673545
TI  - Serum levels of fractalkine are associated with markers of insulin resistance in
      gestational diabetes.
AB  - AIMS: Fractalkine has recently been introduced as an adipokine that improves
      glucose tolerance. Regulation of fractalkine in gestational diabetes, as well as
      its association with markers of obesity, glucose and lipid metabolism,
      inflammation and renal function, has not been elucidated. METHODS: Circulating
      fractalkine was quantified by enzyme-linked immunosorbent assay in 74 women with
      gestational diabetes and 74 healthy, pregnant control subjects matched for age,
      BMI, and gestational age. RESULTS: Median (interquartile range) levels of
      fractalkine were not significantly different between the two groups [gestational
      diabetes: 2.24 (2.16) MUg/l; control: 2.45 (1.38) MUg/l] (P = 0.461). In
      multivariate linear regression analysis, fractalkine remained independently
      associated with homeostasis model assessment of insulin resistance (beta = 
      0.253, P = 0.002) and the proinflammatory adipokine progranulin (beta = 0.218, P
      = 0.007). CONCLUSIONS: Circulating fractalkine is not different between women
      with gestational diabetes and control subjects, but the adipokine is
      independently associated with markers of insulin resistance and proinflammatory
      progranulin in pregnancy.

PMID- 24673547
TI  - Effect of various commercial buffers on sperm viability and capacitation.
AB  - A wide variety of sperm preparation protocols are currently available for
      assisted conception. They include density gradient separation and washing
      methods. Both aim at isolating and capacitating as much motile sperm as possible
      for subsequent oocyte fertilization. The aim of this study was to examine the
      effects of four commercial sperm washing buffers on sperm viability and
      capacitation. Semen samples from 48 healthy donors (normal values of sperm count,
      motility, morphology, and volume) were analyzed. After separation (density
      gradient 40/80%), sperm were incubated in various buffers then analysed for
      reactive oxygen species (ROS) production, viability, tyrosine phosphorylation
      (Tyr-P), cholera toxin B subunit (CTB) labeling, and the acrosome reaction (AR).
      The buffers affected ROS generation in various ways resulting either in rapid
      cell degeneration (when the amount of ROS was too high for cell survival) or the
      inability of the cells to maintain correct functioning (when ROS were too few).
      Only when the correct ROS generation curve was maintained, suitable membrane
      reorganization, evidenced by CTB labeling was achieved, leading to the highest
      percentages of both Tyr-P- and acrosome-reacted-cells. Distinguishing each
      particular pathological state of the sperm sample would be helpful to select the
      preferred buffer treatment since both ROS production and membrane reorganization
      can be significantly altered by commercial buffers.

PMID- 24673548
TI  - HLA-B*40:02:18, a new HLA-B*40 allele.
AB  - The new allele B*40:02:18 showed one nucleotide difference with B*40:02:01 at
      codon 111 (CGC/CGT). 

PMID- 24673546
TI  - Two pathways toward impulsive action: an integrative risk model for bulimic
      behavior in youth.
AB  - BACKGROUND: This study provides an integrative review of existing risk factors
      and models for bulimia nervosa (BN) in young girls. We offer a new model for BN
      that describes two pathways of risk that may lead to the initial impulsive act of
      binge eating and purging in children and adolescents. SCOPE: We conducted a
      selective literature review, focusing on existing and new risk processes for BN
      in this select population. FINDINGS: We identify two ways in which girls increase
      their risk to begin engaging in the impulsive behavior of binge eating and
      purging. The first is state-based: the experience of negative mood, in girls
      attempting to restrain eating, leads to the depletion of self-control and thus
      increased risk for loss of control eating. The second is personality-based:
      elevations on the trait of negative urgency, or the tendency to act rashly when
      distressed, increase risk, particularly in conjunction with high-risk
      psychosocial learning. We then briefly discuss how these behaviors are
      reinforced, putting girls at further risk for developing BN. CONCLUSIONS: We
      highlight several areas in which further inquiry is necessary, and we discuss the
      clinical implications of the new risk model we described.

PMID- 24673549
TI  - Recurrent longitudinal extensive transverse myelitis in a neuro-Behcet syndrome
      treated with infliximab.
AB  - BACKGROUND: Spinal cord involvement is not common, but can be seen in neuro
      Behcet's syndrome (NBS). The major site of involvement is the cervical spinal
      cord with the myelitis-like inflammatory lesions continuing more than two
      segments, and extending to the brainstem. CASE: A 30-year-old male patient who
      has been followed with a diagnosis of Behcet's syndrome admitted to our neurology
      department clinically and radiologically suggestive of recurrent and extensive
      longitudinal myelitis. His anti-aquaporine antibody was negative. Because of
      insufficient effect of azathioprine, cyclophosphamide, and corticosteroids,
      infliximab was started. His clinical and radiological status is stationary for 3
      years under infliximab treatment. DISCUSSION: Myelitis such as that occurring in
      our patient may have a similar presentation like neuromyelitis optica (NMO),
      which should therefore be included in differential diagnosis. Myelitis observed
      in both NMO and NBS shows spinal cord lesions longer than three or more
      vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting
      with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be
      an alternative treatment in severe form of NBS such as myelitis. CONCLUSION: In
      our case, successful treatment of recurrent and extensive longitudinal transverse
      myelitis in NBS with infliximab was demonstrated.

PMID- 24673550
TI  - Validity of birth certificate-derived maternal weight data.
AB  - BACKGROUND: Studies using vital records-based maternal weight data have become
      more common, but the validity of these data is uncertain. METHODS: We evaluated
      the accuracy of prepregnancy body mass index (BMI) and gestational weight gain
      (GWG) reported on birth certificates using medical record data in 1204 births at
      a teaching hospital in Pennsylvania from 2003 to 2010. Deliveries at this
      hospital were representative of births statewide with respect to BMI, GWG,
      race/ethnicity, and preterm birth. Forty-eight strata were created by
      simultaneous stratification on prepregnancy BMI (underweight, normal
      weight/overweight, obese class 1, obese classes 2 and 3), GWG (<20th, 20-80th,
      >80th percentile), race/ethnicity (non-Hispanic white, non-Hispanic black), and
      gestational age (term, preterm). RESULTS: The agreement of birth certificate
      derived prepregnancy BMI category with medical record BMI category was highest in
      the normal weight/overweight and obese class 2 and 3 groups. Agreement varied
      from 52% to 100% across racial/ethnic and gestational age strata. GWG category
      from the birth registry agreed with medical records for 41-83% of deliveries, and
      agreement tended to be the poorest for very low and very high GWG. The
      misclassification of GWG was driven by errors in reported prepregnancy weight
      rather than maternal weight at delivery, and its magnitude depended on
      prepregnancy BMI category and gestational age at delivery. CONCLUSIONS: Maternal
      weight data, particularly at the extremes, are poorly reported on birth
      certificates. Investigators should devote resources to well-designed validation
      studies, the results of which can be used to adjust for measurement errors by
      bias analysis.

PMID- 24673551
TI  - Comparative study on novel test systems to determine disintegration time of
      orodispersible films.
AB  - OBJECTIVES: Orodispersible films (ODFs) are a promising innovative dosage form
      enabling drug administration without the need for water and minimizing danger of
      aspiration due to their fast disintegration in small amounts of liquid. This
      study focuses on the development of a disintegration test system for ODFs.
      METHODS: Two systems were developed and investigated: one provides an electronic
      end-point, and the other shows a transferable setup of the existing
      disintegration tester for orodispersible tablets. Different ODF preparations were
      investigated to determine the suitability of the disintegration test systems. The
      use of different test media and the impact of different storage conditions of
      ODFs on their disintegration time were additionally investigated. KEY FINDINGS:
      The experiments showed acceptable reproducibility (low deviations within sample
      replicates due to a clear determination of the measurement end-point). High
      temperatures and high humidity affected some of the investigated ODFs, resulting
      in higher disintegration time or even no disintegration within the tested time
      period. CONCLUSIONS: The methods provided clear end-point detection and were
      applicable for different types of ODFs. By the modification of a conventional
      test system to enable application for films, a standard method could be presented
      to ensure uniformity in current quality control settings.

PMID- 24673552
TI  - Pharmacological management of polycystic kidney disease.
AB  - INTRODUCTION: Autosomal-dominant polycystic kidney disease (ADPKD) represents a
      therapeutic challenge as effective treatment to retard the growth of cysts in the
      kidneys and the liver has not been available despite decades of intense basic and
      clinical research. AREAS COVERED: Several clinical trials have been performed in
      recent years to study the effect of diverse drugs on the growth of renal and
      hepatic cysts, and on functional deterioration of the glomerular filtration rate.
      The drug classes that have been tested in randomized clinical trials include the
      mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, the
      somatostatin analogues (octreotide, lanreotide, pasireotide), and most recently,
      the vasopressin V2 receptor antagonist, tolvaptan. The results with the mTOR
      inhibitors were disappointing, but more encouraging with the somatostatin
      analogues and with tolvaptan. Additional drugs are being tested, which include
      among others, the SRC-ABL tyrosine kinase inhibitor, bosutinib, and the
      traditional Chinese herbal medication, triptolide. Additional therapeutic
      strategies to retard cyst growth aim at blood pressure control via inhibition of
      the renin-angiotensin system and the sympathetic nervous system. EXPERT OPINION:
      Given the accumulated knowledge, it is currently uncertain whether drugs will
      become available in the near future to significantly change the course of the
      relentlessly progressing polycystic kidney disease.

PMID- 24673553
TI  - Sleep difficulty mediates effects of vasomotor symptoms on mood in younger breast
      cancer survivors.
AB  - OBJECTIVE: Treatment-induced early menopause occurs in > 80% of premenopausal
      women diagnosed with breast cancer. This study explored the relationship between
      vasomotor symptoms (VMS), sleep and mood in women aged 40-51 years with non
      metastatic breast cancer. METHODS: Cross-sectional study using validated
      questionnaires (Greene Climacteric scale and Hospital Anxiety and Depression
      Scale, HADS). Women (n = 114) were recruited from the community and hospital
      outpatient clinics. Frequency determination and structural equation modeling
      (SEMod) were used to examine the relationship between the latent variables: VMS,
      anxiety, and depression, and the indicator variable: difficulty sleeping.
      RESULTS: Participants' mean age was 47 years and 94% became menopausal after
      breast cancer diagnosis. Difficulty sleeping was reported by 82% of women with
      46% reporting (Likert scale) 'quite a bit/extremely'. Most women reported night
      sweats (77% of women: 47% reporting 'quite a bit/extremely') and hot flushes (84%
      of women: 50% reporting 'quite a bit/extremely'). HADS scores indicated
      clinically relevant depression and anxiety in 98% and 99% of women, respectively.
      SEMod revealed that VMS contributed to difficulty sleeping (standardized
      coefficient = 0.54; p < 0.001) and difficulty sleeping mediated the relationship
      between VMS and anxiety (standardized coefficient = 0.34; p = 0.03). However,
      difficulty sleeping did not have a significant direct impact on depression
      (standardized coefficient = -0.03; p = 0.8), although anxiety was a strong
      predictor of depression (standardized coefficient = 0.83; p = 0.015).
      CONCLUSIONS: VMS, sleep and mood disturbance are commonly experienced by younger
      women with breast cancer. Using SEMod, we demonstrate for the first time that VMS
      may directly influence sleep in these women. VMS may have an indirect effect on
      mood, partly mediated by sleep difficulty.

PMID- 24673554
TI  - Biomimetic microfluidic device for in vitro antihypertensive drug evaluation.
AB  - Microfluidic devices have emerged as revolutionary, novel platforms for in vitro
      drug evaluation. In this work, we developed a facile method for evaluating
      antihypertensive drugs using a microfluidic chip. This microfluidic chip was
      generated using the elastic material poly(dimethylsiloxane) (PDMS) and a
      microchannel structure that simulated a blood vessel as fabricated on the chip.
      We then cultured human umbilical vein endothelial cells (HUVECs) inside the
      channel. Different pressures and shear stresses could be applied on the cells.
      The generated vessel mimics can be used for evaluating the safety and effects of
      antihypertensive drugs. Here, we used hydralazine hydrochloride as a model drug.
      The results indicated that hydralazine hydrochloride effectively decreased the
      pressure-induced dysfunction of endothelial cells. This work demonstrates that
      our microfluidic system provides a convenient and cost-effective platform for
      studying cellular responses to drugs under mechanical pressure. 

PMID- 24673555
TI  - The effect of previous traumatic injury on homicide risk.
AB  - Research has reported that a strong risk factor for traumatic injury is having a
      previous injury (i.e., recidivism). To date, the only study examining the
      relationship between recidivism and homicide reported strong associations, but
      was limited by possible selection bias. The current matched case-control study
      utilized coroner's data from 2004 to 2008. Subjects were linked to trauma
      registry data to determine whether the person had a previous traumatic injury.
      Conditional logistic regression was used to estimate odds ratios (ORs) and 95%
      confidence intervals (95% CIs) for the association between homicide and
      recidivism. Homicide risk was increased for those having a previous traumatic
      injury (OR 1.81, 95% CI 1.09-2.99) or a previous intentional injury (OR 2.53, 95%
      CI 1.24-5.17). These results suggest an association between homicide and injury
      recidivism, and that trauma centers may be an effective setting for screening
      individuals for secondary prevention efforts of homicide through violence
      prevention programs. 

PMID- 24673556
TI  - Invasive breast cancer: stratification of histological grade by gene-based
      assays: a still relevant example from an older data set.
AB  - AIMS: A Netherlands Kanker Institute data set provided the results of gene-based
      assays (GBAs) and histological grades of 295 patients with invasive breast
      cancer. Grade is the first prognostic assay available after a cancer diagnosis.
      Given this time-line of actual practise, the aim was to study how gene-based
      assays further stratify histologic grade. METHODS AND RESULTS: Emphasis was
      placed on evaluation of a simple decision tree and on study of the recurrence
      score (RS). The decision tree determined three risk stratifications. Tumours that
      were both intermediate grade (IG) and low-RS were grouped with low grade, and
      tumours that were IG and high-RS were coupled with high grade. IG and
      intermediate-RS tumours comprised the third category. Survival analysis was
      performed with respect to the three stratifications. Cramer's V statistic was
      used for concordance analysis. The mixed grade-RS classifier showed significant
      survival stratification (P < 0.00001). The mixed classifier was concordant with
      the 70-gene assay (Cramer's V = 0.57). Recurrence score alone had a 0.59 Cramer's
      V with the gene assay. Because two-thirds of tumours were of either low or high
      grade, concordance was maintained despite the majority of classifications having
      been determined by grade alone. CONCLUSION: There is no compelling reason to test
      low- and high-grade tumours further by GBAs.

PMID- 24673557
TI  - Hepatocyte growth factor and p38 promote osteogenic differentiation of human
      mesenchymal stem cells.
AB  - Hepatocyte growth factor (HGF) is a paracrine factor involved in organogenesis,
      tissue repair, and wound healing. We report here that HGF promotes osteogenic
      differentiation through the transcription of key osteogenic markers, including
      osteocalcin, osterix, and osteoprotegerin in human mesenchymal stem cells and is
      a necessary component for the establishment of osteoblast mineralization.
      Blocking endogenous HGF using PHA665752, a c-Met inhibitor (the HGF receptor), or
      an HGF-neutralizing antibody attenuates mineralization, and PHA665752 markedly
      reduced alkaline phosphatase activity. Moreover, we report that HGF promotion of
      osteogenic differentiation involves the rapid phosphorylation of p38 and
      differential regulation of its isoforms, p38alpha and p38beta. Western blot
      analysis revealed a significantly increased level of p38alpha and p38beta
      protein, and reverse transcription quantitative PCR revealed that HGF increased
      the transcriptional level of both p38alpha and p38beta. Using small interfering
      RNA to reduce the transcription of p38alpha and p38beta, we saw differential
      roles for p38alpha and p38beta on the HGF-induced expression of key osteogenic
      markers. In summary, our data demonstrate the importance of p38 signaling in HGF
      regulation of osteogenic differentiation.

PMID- 24673558
TI  - The ability of thyroid hormone receptors to sense t4 as an agonist depends on
      receptor isoform and on cellular cofactors.
AB  - T4 (3,5,3',5'-tetraiodo-l-thyronine) is classically viewed as a prohormone that
      must be converted to the T3 (3,5,3'-triiodo-l-thyronine) form for biological
      activity. We first determined that the ability of reporter genes to respond to T4
      and to T3 differed for the different thyroid hormone receptor (TR) isoforms, with
      TRalpha1 generally more responsive to T4 than was TRbeta1. The response to T4 vs
      T3 also differed dramatically in different cell types in a manner that could not
      be attributed to differences in deiodinase activity or in hormone affinity,
      leading us to examine the role of TR coregulators in this phenomenon.
      Unexpectedly, several coactivators, such as steroid receptor coactivator-1 (SRC1)
      and thyroid hormone receptor-associated protein 220 (TRAP220), were recruited to
      TRalpha1 nearly equally by T4 as by T3 in vitro, indicating that TRalpha1
      possesses an innate potential to respond efficiently to T4 as an agonist. In
      contrast, release of corepressors, such as the nuclear receptor coreceptor
      NCoRomega, from TRalpha1 by T4 was relatively inefficient, requiring considerably
      higher concentrations of this ligand than did coactivator recruitment. Our
      results suggest that cells, by altering the repertoire and abundance of
      corepressors and coactivators expressed, may regulate their ability to respond to
      T4, raising the possibility that T4 may function directly as a hormone in
      specific cellular or physiological contexts.

PMID- 24673559
TI  - Notch signaling in postnatal pituitary expansion: proliferation, progenitors, and
      cell specification.
AB  - Mutations in PROP1 account for up to half of the cases of combined pituitary
      hormone deficiency that result from known causes. Despite this, few signaling
      molecules and pathways that influence PROP1 expression have been identified.
      Notch signaling has been linked to Prop1 expression, but the developmental
      periods during which Notch signaling influences Prop1 and overall pituitary
      development remain unclear. To test the requirement for Notch signaling in
      establishing the normal pituitary hormone milieu, we generated mice with early
      embryonic conditional loss of Notch2 (conditional knockout) and examined the
      consequences of chemical Notch inhibition during early postnatal pituitary
      maturation. We show that loss of Notch2 has little influence on early embryonic
      pituitary proliferation but is crucial for postnatal progenitor maintenance and
      proliferation. In addition, we show that Notch signaling is necessary
      embryonically and postnatally for Prop1 expression and robust Pit1 lineage
      hormone cell expansion, as well as repression of the corticotrope lineage. Taken
      together, our studies identify temporal and cell type-specific roles for Notch
      signaling and highlight the importance of this pathway throughout pituitary
      development.

PMID- 24673561
TI  - Myosin VIIa and otoferlin in cochlear inner hair cells have distinct response to
      ototoxic exposure.
AB  - CONCLUSION: Ototoxic gentamicin exposure does not disrupt the expression of
      myosin VIIa in the inner hair cells (IHCs) of mice, whereas gentamicin
      ototoxicity causes altered expression of otoferlin in IHCs, as well as parallel
      hearing threshold shifts. OBJECTIVE: To explore whether myosin VIIa and otoferlin
      in IHCs have different responses to gentamicin ototoxicity. METHODS: Lower dose
      treatment (100 mg/kg): adult C57 mice were continuously injected
      intraperitoneally with gentamicin once a day for 14 consecutive days. Dose
      dependent gentamicin treatment: mice were injected intraperitoneally with
      differing doses (100, 200, and 300 mg/kg) once a day for 2 consecutive days. The
      hearing thresholds were detected by auditory brainstem response (ABR).
      Immunostaining and Western blotting were utilized to measure the manner of
      expression of myosin VIIa and otoferlin in IHCs. RESULTS: Lower dose treatment:
      There were no significant differences among the control (day 0), and 4, 7, and 14
      days after the ototoxicity exposure (p > 0.05). Dose-dependent gentamicin
      treatment: There were no significant differences among the control, 100, 200, and
      300 mg/kg groups after the ototoxicity exposure (p > 0.05). In contrast, we found
      an altered expression of otoferlin in IHCs among the control (day 0), and 4, 7,
      and 14 days of exposure, when the mice were exposed to gentamicin ototoxicity (p
      > 0.05).

PMID- 24673560
TI  - Hospital and geographic variability in thirty-day all-cause mortality following
      colorectal cancer surgery.
AB  - OBJECTIVE: To assess hospital and geographic variability in 30-day mortality
      after surgery for CRC and examine the extent to which sociodemographic, area
      level, clinical, tumor, treatment, and hospital characteristics were associated
      with increased likelihood of 30-day mortality in a population-based sample of
      older CRC patients. DATA SOURCES/STUDY SETTING: Linked Surveillance Epidemiology
      End Results (SEER) and Medicare data from 47,459 CRC patients aged 66 years or
      older who underwent surgical resection between 2000 and 2005, resided in 13,182
      census tracts, and were treated in 1,447 hospitals. STUDY DESIGN: An
      observational study using multilevel logistic regression to identify hospital-
      and patient-level predictors of and variability in 30-day mortality. DATA
      COLLECTION/EXTRACTION METHODS: We extracted sociodemographic, clinical, tumor,
      treatment, hospital, and geographic characteristics from Medicare claims, SEER,
      and census data. PRINCIPAL FINDINGS: Of 47,459 CRC patients, 6.6 percent died
      within 30 days following surgery. Adjusted variability in 30-day mortality
      existed across residential census tracts (predicted mortality range: 2.7-12.3
      percent) and hospitals (predicted mortality range: 2.5-10.5 percent). Higher risk
      of death within 30 days was observed for CRC patients age 85+ (12.7 percent),
      census-tract poverty rate >20 percent (8.0 percent), two or more comorbid
      conditions (8.8 percent), stage IV at diagnosis (15.1 percent), undifferentiated
      tumors (11.6 percent), and emergency surgery (12.8 percent). CONCLUSIONS:
      Substantial, but similar variability was observed across census tracts and
      hospitals in 30-day mortality following surgery for CRC in patients 66 years and
      older. Risk of 30-day mortality is driven not only by patient and hospital
      characteristics but also by larger social and economic factors that characterize
      geographic areas.

PMID- 24673562
TI  - Effect of serum interleukin 21 on the development of coronary artery disease.
AB  - There has been more and more evidence to confirm the essential role of
      inflammatory processes in the development of coronary artery disease (CAD).
      Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine,
      plays a key role in regulating inflammation. The aim of the study was to
      understand the effect of peripheral IL-21 on the pathogenesis and progression of
      CAD. Serum level of IL-21 in 92 CAD patients and 73 controls was measured by the
      enzyme-linked immunosorbent assay. Data showed that IL-21 expression was
      significantly increased in CAD than in controls (p < 0.001). Interestingly, when
      comparing IL-21 level with different genders, male subjects revealed higher IL-21
      than female subjects (p = 0.024). Also, we observed that patients with
      hypertension had upregulated level of serum IL-21 (p = 0.002). Moreover, serum
      level of IL-21 was positively correlated with total cholesterol level (p = 0.015)
      or low-density lipoprotein cholesterol (p = 0.0009) of CAD cases. In addition, we
      analyzed IL-21 level with the severity of CAD, and identified that cases with 3
      vessel affected had significantly elevated level of IL-21 than those with 1
      vessel or 2-vessel affected. These data suggested that serum level of IL-21 may
      be closely associated with the development and progression of CAD. 

PMID- 24673563
TI  - Semen characteristics of captive common marmoset (Callithrix jacchus): a
      comparison of a German with a Brazilian colony.
AB  - BACKGROUND: The common marmoset (Callithrix jacchus) is of interest for
      reproductive studies because of their high and variable fertility in captivity.
      However, to understand this variability, much basic information still needs to be
      gathered. This study is the first to characterize marmoset semen comparing a
      German and a Brazilian colony. METHODS: All animals were weighted, and semen
      samples were collected by penile vibratory stimulation and analyzed according to
      standard criteria. RESULTS AND CONCLUSIONS: The German animals had a higher mean
      and maximum weight than the Brazilian. Further, sperm concentration tended to be
      higher with heavier animals in the German population, but not in the Brazilian.
      Additionally, major defects tended to be more frequent with higher weight but
      also only in German sample. In spite of these differences, the total range and
      variability in sperm concentration were similar in both populations, suggesting
      that this is characteristic for the species.

PMID- 24673564
TI  - The pKa value and accessibility of cysteine residues are key determinants for
      protein substrate discrimination by glutaredoxin.
AB  - The enzyme glutaredoxin catalyzes glutathione exchange, but little is known about
      its interaction with protein substrates. Very different proteins are substrates
      in vitro, and the enzyme seems to have low requirements for specific protein
      interactions. Here we present a systematic investigation of the interaction
      between human glutaredoxin 1 and glutathionylated variants of a single model
      protein. Thus, single cysteine variants of acyl-coenzyme A binding protein were
      produced creating a set of substrates in the same protein background. The rate
      constants for deglutathionylation differ by more than 2 orders of magnitude
      between the best (k1 = 1.75 * 10(5) M(-1) s(-1)) and the worst substrate (k1 = 4
      * 10(2) M(-1) s(-1)). The pKa values of the substrate cysteine residues were
      determined by NMR spectroscopy and found to vary from 8.2 to 9.9. Rates of
      glutaredoxin 1-catalyzed deglutathionylation were assessed with respect to
      substrate cysteine pKa values, cysteine residue accessibility, local stability,
      and backbone dynamics. Good substrates are characterized by a combination of high
      accessibility of the glutathionylated site and low pKa of the cysteine residue. 

PMID- 24673566
TI  - Cytotoxic reaction mediators: granzymes A and B in women with ovarian cancer.
AB  - The purpose of this work was the assessment of cytotoxic reaction mediators -
      granzymes A and B in the serum of women with ovarian tumors. The study included
      120 women with proven ovarian tumors. The control group consisted of 60 healthy
      women in whom no pathological changes within the reproductive system were
      detected. Concentrations of granzymes A and B were measured by enzyme-linked
      immunosorbent (ELISA) assay. The highest concentrations of the studied parameters
      were observed in serum of women with ovarian cancer. Moreover, the concentrations
      of granzymes A and B in patients with ovarian cancer were substantially increased
      in comparison to concentrations in patients with ovarian cystadenomas (P <
      0.0001) or ovarian teratomas (P < 0.0001).

PMID- 24673565
TI  - Bioreducible cationic polymer-based nanoparticles for efficient and
      environmentally triggered cytoplasmic siRNA delivery to primary human brain
      cancer cells.
AB  - siRNA nanomedicines can potentially treat many human diseases, but safe and
      effective delivery remains a challenge. DNA delivery polymers such as poly(beta
      amino ester)s (PBAEs) generally cannot effectively deliver siRNA and require
      chemical modification to enable siRNA encapsulation and delivery. An optimal
      siRNA delivery nanomaterial needs to be able to bind and self-assemble with siRNA
      molecules that are shorter and stiffer than plasmid DNA in order to form stable
      nanoparticles, and needs to promote efficient siRNA release upon entry to the
      cytoplasm. To address these concerns, we designed, synthesized, and characterized
      an array of bioreducible PBAEs that self-assemble with siRNA in aqueous
      conditions to form nanoparticles of approximately 100 nm and that exhibit
      environmentally triggered siRNA release upon entering the reducing environment of
      the cytosol. By tuning polymer properties, including bioreducibility and
      hydrophobicity, we were able to fabricate polymeric nanoparticles capable of
      efficient gene knockdown (91 +/- 1%) in primary human glioblastoma cells without
      significant cytotoxicity (6 +/- 12%). We were also able to achieve significantly
      higher knockdown using these polymers with a low dose of 5 nM siRNA (76 +/- 14%)
      compared to commercially available reagent Lipofectamine 2000 with a 4-fold
      higher dose of 20 nM siRNA (40 +/- 7%). These bioreducible PBAEs also enabled 63
      +/- 16% gene knockdown using an extremely low 1 nM siRNA dose and showed
      preferential transfection of glioblastoma cells versus noncancer neural
      progenitor cells, highlighting their potential as efficient and tumor-specific
      carriers for siRNA-based nanomedicine. 

PMID- 24673567
TI  - Multidisciplinary clinical strategies for encapsulating peritoneal sclerosis in
      peritoneal dialysis: update from Japan.
AB  - Peritoneal dialysis is established as a first-line standard renal replacement
      therapy for end-stage renal disease. However, the development of encapsulating
      peritoneal sclerosis has been a critical complication among long-term peritoneal
      dialysis patients. During the past decade, multidisciplinary approaches have been
      used to suppress encapsulating peritoneal sclerosis. The present article reviews
      the historical and present status of encapsulating peritoneal sclerosis in Japan.

PMID- 24673568
TI  - Laser-engineered dissolving microneedle arrays for protein delivery: potential
      for enhanced intradermal vaccination.
AB  - OBJECTIVES: We aimed to highlight the utility of novel dissolving microneedle
      (MN)-based delivery systems for enhanced transdermal protein delivery.
      Vaccination remains the most accepted and effective approach in offering
      protection from infectious diseases. In recent years, much interest has focused
      on the possibility of using minimally invasive MN technologies to replace
      conventional hypodermic vaccine injections. METHODS: The focus of this study was
      exploitation of dissolving MN array devices fabricated from 20% w/w poly(methyl
      vinyl ether/maleic acid) using a micromoulding technique, for the facilitated
      delivery of a model antigen, ovalbumin (OVA). KEY FINDINGS: A series of in-vitro
      and in-vivo experiments were designed to demonstrate that MN arrays loaded with
      OVA penetrated the stratum corneum and delivered their payload systemically. The
      latter was evidenced by the activation of both humoral and cellular inflammatory
      responses in mice, indicated by the production of immunoglobulins (IgG, IgG1,
      IgG2a) and inflammatory cytokines, specifically interferon-gamma and interleukin
      4. Importantly, the structural integrity of the OVA following incorporation into
      the MN arrays was maintained. CONCLUSION: While enhanced manufacturing strategies
      are required to improve delivery efficiency and reduce waste, dissolving MN are a
      promising candidate for 'reduced-risk' vaccination and protein delivery
      strategies.

PMID- 24673569
TI  - Local spatial and temporal factors influencing population and societal
      vulnerability to natural disasters.
AB  - The identification of societal vulnerable counties and regions and the factors
      contributing to social vulnerability are crucial for effective disaster risk
      management. Significant advances have been made in the study of social
      vulnerability over the past two decades, but we still know little regarding
      China's societal vulnerability profiles, especially at the county level. This
      study investigates the county-level spatial and temporal patterns in social
      vulnerability in China from 1980 to 2010. Based on China's four most recent
      population censuses of 2,361 counties and their corresponding socioeconomic data,
      a social vulnerability index for each county was created using factor analysis.
      Exploratory spatial data analysis, including global and local autocorrelations,
      was applied to reveal the spatial patterns of county-level social vulnerability.
      The results demonstrate that the dynamic characteristics of China's county-level
      social vulnerability are notably distinct, and the dominant contributors to
      societal vulnerability for all of the years studied were rural character,
      development (urbanization), and economic status. The spatial clustering patterns
      of social vulnerability to natural disasters in China exhibited a gathering
      scattering-gathering pattern over time. Further investigations indicate that many
      counties in the eastern coastal area of China are experiencing a detectable
      increase in social vulnerability, whereas the societal vulnerability of many
      counties in the western and northern areas of China has significantly decreased
      over the past three decades. These findings will provide policymakers with a
      sound scientific basis for disaster prevention and mitigation decisions. 

PMID- 24673570
TI  - Mechanism study of cellular uptake and tight junction opening mediated by goblet
      cell-specific trimethyl chitosan nanoparticles.
AB  - Modifying nanoparticles with targeting peptides which can specifically bind to
      intestinal epithelium was recently suggested as a strategy to further enhance
      their ability for the oral delivery of macromolecular drugs. However, few studies
      were focused on comprehensive understanding of the uptake and transport processes
      as well as the underlying molecular signaling pathways mediated by the ligand
      modification. In the present study, the mechanisms of cellular uptake and the
      tight junction opening associated with the trimethyl chitosan based nanoparticles
      (M-NPs) and their goblet cell-targeting CSK (CSKSSDYQC) peptide modified
      nanoparticles (CSK-M-NPs) were investigated. Compared with single ion cross
      linked nanoparticles (S NPs), M-NPs and CSK-M-NPs, prepared with multiple agents,
      exhibited superior stability which could effectively protect drugs against the
      degradation of trypsin. Caveolae-mediated endocytosis and macropinocytosis were
      involved in the intracellular uptake of both M-NPs and CSK-M-NPs on Caco-2/HT29
      MTX cocultured cells. However, CSK peptide modification could further induce
      clathrin-mediated endocytosis of the NPs. Intriguingly, most endocytosis
      subpathways have been altered after CSK peptide modification. Moreover, the
      opening of epithelial tight junctions was investigated at both protein and gene
      levels. The results indicated that both M-NPs and CSK-M-NPs could transiently and
      reversibly open the epithelial tight junctions via the C-Jun NH2-terminal kinase
      dependent pathway. However, CSK peptide modification enabled a more rapid opening
      and recovering of the tight junctions. In all, the enhanced uptake and transport
      capacity of nanoparticles after CSK peptide modification may be attributed to the
      alteration of internalization pathways and the stronger ability of opening tight
      junctions. 

PMID- 24673571
TI  - Psychological and pharmacological interventions for depression in patients with
      diabetes mellitus: an abridged Cochrane review.
AB  - AIMS: To summarize and critically evaluate the effectiveness of psychological and
      pharmacological interventions for depression in patients with both diabetes and
      depression. METHODS: Randomized controlled trials investigating psychological and
      pharmacological interventions for depression in adults with diabetes and
      depression were included. A comprehensive search of primary studies according to
      Cochrane were conducted. Primary outcomes were depression and glycaemic control.
      Further, treatment adherence, diabetes complications, mortality, healthcare costs
      and quality of life were investigated. Two reviewers identified primary studies
      and extracted data independently. Random-effects model meta-analyses were
      conducted to compute overall estimates of treatment outcomes. RESULTS: The
      database search resulted in 3963 references, of which 19 trials were included.
      Randomized controlled trials of psychological interventions showed positive
      effects on short- and medium-term depression severity [standardized mean
      difference short-term range -1.47; -0.14, n = 7; medium-term standardized mean
      difference -0.42 (95% CI -0.70 to -0.14), n = 3] and depression remission [odds
      ratio short term 2.88 (95% CI 1.58-5.25), n = 4; odds ratio medium term 2.49 (95%
      CI 1.44-4.32), n = 2]. Effects on glycaemic control in psychological intervention
      trials varied substantially (standardized mean difference range -0.97 to 0.47, n
      = 4). Selective serotonin reuptake inhibitors showed a moderate beneficial effect
      on short-term depression severity [standardized mean difference -0.39 (95% CI 
      0.64 to -0.13], n = 5) and depression remission [odds ratio 2.52 (95% CI 1.11
      5.75), n = 2]. Glycaemic control improved in randomized controlled trials
      comparing selective serotonin reuptake inhibitors with placebo at the end of
      treatment [standardized mean difference -0.38 (95% CI -0.64 to -0.12), n = 5].
      CONCLUSIONS: Psychological and pharmacological interventions positively affect
      depression outcomes in patients with diabetes at the end of treatment.
      Furthermore, short-term glycaemic control improved moderately in pharmacological
      trials. Most outcomes have not been investigated sufficiently. Moreover, there is
      a lack of follow-up data for pharmacological trials limiting the evidence on the
      sustainability of treatment effects.

PMID- 24673572
TI  - Pharmacotherapy of bone metastases in breast cancer patients--an update.
AB  - INTRODUCTION: Bone metastases in breast cancer patients are a common clinical
      problem and pose a threat to the quality of life of such patients. Multiple
      randomized trials have demonstrated the benefit of both bisphosphonates and
      denosumab in reducing the incidence and delaying the onset of skeletal related
      events (SREs) in breast cancer patients with bone metastases. AREAS COVERED: We
      review the current literature on the use of bisphosphonates and denosumab along
      with strategies to maximize benefit and minimize risk of these agents. We also
      review potential future targets. EXPERT OPINION: Despite the potent osteoclast
      inhibiting effects of the bone-targeted agents in current clinical use, we have
      likely maximized their ability to inhibit SREs and must in turn focus on
      minimizing their potential toxicity. The future will likely involve more novel
      treatment strategies as well as the development of new agents. The current 'one
      size fits all' approach for the management of breast cancer bone metastases will
      be replaced by 'tailored' treatment for each individual patient as we usher in
      the era of 'personalized medicine.' In addition, new bone-targeted agents (e.g.,
      sclerostin inhibitors) and combinations will continue to be explored, as will the
      evaluation of the bone-targeting properties of more conventional non-osteoclast
      targeting therapies.

PMID- 24673573
TI  - Patterned substrates of nano-graphene oxide mediating highly localized and
      efficient gene delivery.
AB  - A facile approach was developed to fabricate patterned substrates of nano
      graphene oxide, demonstrating highly localized and efficient gene delivery to
      multiple cell lines in a substrate-mediated manner. The GO substrates served as a
      valid platform to preconcentrate PEI/pDNA complexes and maintain their gradual
      releasing for a relatively long period of time. Our approach allowed successful
      gene delivery in selected groups of cells on the stripe-patterned GO substrates,
      without transfecting their neighbor cells directly cultured on glass. These GO
      substrates exhibited excellent biocompatibility and enabled effective gene
      transfection for various cell lines including stem cells, thus promising
      important applications in stem cell research and tissue engineering. 

PMID- 24673574
TI  - Mutations in the SPTLC1 protein cause mitochondrial structural abnormalities and
      endoplasmic reticulum stress in lymphoblasts.
AB  - Mutations in serine palmitoyltransferase long chain subunit 1 (SPTLC1) cause the
      typical length-dependent axonal degeneration hereditary sensory neuropathy type 1
      (HSN1). Transmission electron microscopy studies on SPTLC1 mutant lymphoblasts
      derived from patients revealed specific structural abnormalities of mitochondria.
      Swollen mitochondria with abnormal cristae were clustered around the nucleus,
      with some mitochondria being wrapped in rough endoplasmic reticulum (ER)
      membranes. Total mitochondrial counts revealed a significant change in
      mitochondrial numbers between healthy and diseased lymphocytes but did not reveal
      any change in length to width ratios nor were there any changes to cellular
      function. However, there was a notable change in ER homeostasis, as assessed
      using key ER stress markers, BiP and ERO1-Lalpha, displaying reduced protein
      expression. The observations suggest that SPTLC1 mutations cause mitochondrial
      abnormalities and ER stress in HSN1 cells.

PMID- 24673575
TI  - Rapid and sustained systemic circulation of conjugated gut microbial catabolites
      after single-dose black tea extract consumption.
AB  - Gut microbial catabolites of black tea polyphenols (BTPs) have been proposed to
      exert beneficial cardiovascular bioactivity. This hypothesis is difficult to
      verify because the conjugation patterns and pharmacokinetics of these catabolites
      are largely unknown. The objective of our study was to identify, quantify, and
      assess the pharmacokinetics of conjugated BTP metabolites in plasma of healthy
      humans by means of an a priori untargeted LC-MS-based metabolomics approach. In a
      randomized, open, placebo-controlled, crossover study, 12 healthy men consumed a
      single bolus of black tea extract (BTE) or a placebo. The relative and, in
      several cases, absolute concentrations of a wide range of metabolites were
      determined using U(H)PLC-LTQ-Orbitrap-FTMS. Following BTE consumption, a kinetic
      response in plasma was observed for 59 BTP metabolites, 11 of these in a
      quantitative manner. Conjugated and unconjugated catechins appeared in plasma
      without delay, at 2-4 h, followed by a range of microbial catabolites.
      Interindividual variation in response was greater for gut microbial catabolites
      than for directly absorbed BTPs. The rapid and sustained circulation of
      conjugated catabolites suggests that these compounds may be particularly relevant
      to proposed health benefits of BTE. Their presence and effects may depend on
      individual variation in catabolic capacity of the gut microbiota. 

PMID- 24673576
TI  - Countryside species-area relationship as a valid alternative to the matrix
      calibrated species-area model.

PMID- 24673577
TI  - Association between KIR polymorphisms and ankylosing spondylitis in populations:
      a meta-analysis.
AB  - OBJECTIVES: Published association studies of killer cell immunoglobulin-like
      receptors (KIRs) and ankylosing spondylitis (AS) in populations are inconsistent.
      The aim of this study is to determine whether the KIR polymorphisms confer
      susceptibility to AS in populations by conducting a meta-analysis. METHODS: A
      computer search was carried out up to August 2013 for literature pertaining to AS
      and KIR polymorphisms. Publications addressing the association between the KIR
      polymorphisms and susceptibility to AS in populations were selected from the
      Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI)
      and Chinese Biomedical Literature Database (CBM) databases. The odds ratio (OR)
      with 95% confidence interval (95%CI) was calculated. RESULTS: A total of 13 case
      control studies in 9 articles were included in this meta-analysis. Meta-analysis
      results identified two positive associations of 2DS4 and 3DS1 with susceptibility
      to AS in populations. In subgroup analysis, there was a positive association
      between 2DS4 and susceptibility to AS in Asians, but not in Caucasians. And there
      were associations between 3DL1, 3DS1 and susceptibility to AS in Caucasians, but
      not in Asians. Results of subgroup analysis also showed that there were
      associations between 2DL5, 2DS4, 2DS5, 3DL1, 3DS1 and susceptibility to AS in HLA
      B*27-positive patients and HLA-B*27-positive healthy controls. CONCLUSIONS: This
      meta-analysis confirms that 2DS4 and 3DS1 might be potential risk factors for AS
      in populations.

PMID- 24673578
TI  - Chronic unilateral locked facet joint with spinal cord injury in a 26-month-old
      child: A case report.
AB  - OBJECTIVES: This study presents the successful posterior surgical reduction and
      fusion on a 26-month-old child with chronic unilateral locked facet joint and
      spinal cord injury (SCI). METHODS: A 26-month-old child with chronic unilateral
      locked facet joint and SCI treated by posterior surgical reduction and fusion.
      Plaster external fixation was applied and rehabilitation exercise was trained
      post-operatively. RESULTS: Chronic unilateral locked facet joint was reduced
      successfully and bone fusion of C4/5 was achieved 3 months after surgery. The
      function of both lower limbs was improved 1 year after surgery, aided with
      physical rehabilitation. CONCLUSION: Unilateral locked facet joint in pediatric
      population is rare. Few clinical experiences were found in the literature. Non
      surgical treatment has advantages of not being invasive and is preferred for
      acute patients; however, it may not be suitable for chronic unilateral locked
      facet joint with SCI, in which surgical intervention is needed.

PMID- 24673579
TI  - Genotypic tropism prediction from paired cell and plasma using single and
      replicate sequences.
AB  - HIV-1 tropism determination is necessary prior to CCR5 antagonist use as
      antiretroviral therapy. Genotypic prediction of coreceptor use is a practical
      alternative to phenotypic tests. Cell DNA and plasma RNA-based prediction has
      shown discordance in many studies. We evaluate paired cell and plasma either as
      single or replicate V3 sequences to assess prediction comparability. The HIV-1
      partial env region was sequenced and tropism was predicted using geno2pheno and
      position-specific scoring matrices (PSSM). Nucleotide ambiguities at V3 were
      quantified and genetic distance (Protdist) was determined using BioEdit. Wilcoxon
      signed-rank test, t tests, and Spearman correlation were performed with Prism
      GraphPad5.0. Results are expressed as medians, with a level of significance of
      p<0.05, two tailed. Single (n=28) or replicate (n=26) paired cell/plasma
      sequences were obtained from 54 patients. Although the clonalfalse-positive rate
      (FPR) value from both compartments strongly correlated (r=0.86 p<0.0001),
      discordance in tropism prediction was observed in both singles and replicates
      using geno2pheno or PSSM. Applying clonalFPR(10%) 46% (25/54) were X4 tropic,
      with a plasma/cell discordance of 11% in singles and 23% in replicates. Genetic
      distance (p<0.0001) and clonalFPR value dispersion (p=0.003) were significantly
      higher among replicate sequences from cells. Discordance of viral tropism
      prediction is not uncommon and the use of replicates does not decrease its
      occurrence, but improves X4 sensitivity. Sequences from provirus had greater
      genetic distance and dispersion of clonalFPR values. This may suggest that DNA
      replicate assays may better represent the diversity of HIV-1 variants, but the
      clinical significance of these findings needs further evaluation.

PMID- 24673580
TI  - Natural evolution of skin-test sensitivity in patients with IgE-mediated
      hypersensitivity to cephalosporins.
AB  - There are studies demonstrating that skin-test sensitivity to penicillins can
      decrease over time and that allergic patients may lose sensitivity if the
      responsible compounds are avoided. With regard to subjects with IgE-mediated
      hypersensitivity to cephalosporins, however, such studies are lacking. We
      evaluated prospectively in a 5-year follow-up 72 cephalosporin-allergic patients.
      After the first evaluation, patients were classified into two groups according to
      their patterns of allergologic-test positivity: to both penicillins and
      cephalosporins (group A), or only to cephalosporins (group B). Skin tests and
      serum-specific IgE assays were repeated 1 year later and, in case of persistent
      positivity, 3 and 5 years after the first allergologic examination. Seven (43.7%)
      of the 16 subjects of group A and 38 (67.8%) of the 56 patients of group B became
      negative; one was lost to follow-up. Patients of group B became negative sooner
      and more frequently than group A subjects.

PMID- 24673581
TI  - Development and validation of the Liverpool infant bronchiolitis severity score:
      a research protocol.
AB  - AIM: To develop and validate a bronchiolitis severity scoring instrument for use
      by nurses and other healthcare professions. BACKGROUND: Bronchiolitis is a viral
      lower respiratory tract infection of infancy. In industrialized countries,
      admission rates have increased over the last decade with up to 3% of all infants
      born being admitted to hospital. A small number of these hospitalized infants
      will require admission to critical care for either invasive or non-invasive
      ventilation. During the seasonal epidemic, the number of unplanned admissions to
      critical care with bronchiolitis substantially increases. DESIGN: We will use a
      mixed methods study design. METHODS: We will use scale development and
      psychometric methods to develop a scoring instrument and to test the instrument
      for content, construct and criterion validity and reliability in several
      different clinical locations. This study protocol has been reviewed and approved
      by the NHS National Research Ethics Service, January 2011. DISCUSSION: There is
      an urgent need to develop a valid and reliable severity scoring instrument
      sensitive to clinical changes in the infant, to facilitate clinical decision
      making and help standardize patient care. Furthermore, a valid and reliable
      scoring instrument could also be used as a proxy patient-reported outcome measure
      to evaluate the efficacy of clinical interventions in randomized controlled
      trials.

PMID- 24673582
TI  - Benign hereditary chorea: more than meets the eye.

PMID- 24673583
TI  - DNA copy number alterations mark disease progression in paediatric chronic
      myeloid leukaemia.
AB  - Early recognition of children with chronic phase chronic myeloid leukaemia (CML
      CP) at risk for developing a lymphoid blast crisis (LyBC) is desirable, because
      therapy options in CML-LyBC are limited. We used Multiplex Ligation-dependent
      Probe Amplification to determine whether B-cell lymphoid leukaemia-specific copy
      number alterations (CNAs) (e.g. IKZF1, PAX5, CDKN2A deletions) could be detected
      in CML-CP and may be used to predict disease progression to LyBC. CNAs were
      detected in all patients with CML-LyBC, but in none of the 77 patients with CML
      CP. Based on this study we conclude that CNAs remain a hallmark of disease
      progression. 

PMID- 24673585
TI  - Relative immaturity and ADHD: findings from nationwide registers, parent- and
      self-reports.
AB  - BACKGROUND: We addressed if immaturity relative to peers reflected in birth month
      increases the likelihood of ADHD diagnosis and treatment. METHODS: We linked
      nationwide Patient and Prescribed Drug Registers and used prospective cohort and
      nested case-control designs to study 6-69 year-old individuals in Sweden from
      July 2005 to December 2009 (Cohort 1). Cohort 1 included 56,263 individuals
      diagnosed with ADHD or ever used prescribed ADHD-specific medication.
      Complementary population-representative cohorts provided DSM-IV ADHD symptom
      ratings; parent-reported for 10,760 9-year-old twins born 1995-2000 from the
      CATSS study (Cohort 2) and self-reported for 6,970 adult twins age 20-47 years
      born 1959-1970 from the STAGE study (Cohort 3). We calculated odds ratios (OR:s)
      for ADHD across age for individuals born in November/December compared to
      January/February (Cohort 1). ADHD symptoms in Cohorts 2 and 3 were studied as a
      function of calendar birth month. RESULTS: ADHD diagnoses and medication
      treatment were both significantly more common in individuals born in
      November/December versus January/February; peaking at ages 6 (OR: 1.8; 95% CI:
      1.5-2.2) and 7 years (OR: 1.6; 95% CI: 1.3-1.8) in the Patient and Prescribed
      Drug Registers, respectively. We found no corresponding differences in parent- or
      self-reported ADHD symptoms by calendar birth month. CONCLUSION: Relative
      immaturity compared to class mates might contribute to ADHD diagnosis and
      pharmacotherapy despite absence of parallel findings in reported ADHD symptom
      loads by relative immaturity. Increased clinical awareness of this phenomenon may
      be warranted to decrease risk for imprecise diagnostics and treatment. We
      speculate that flexibility regarding age at school start according to individual
      maturity could reduce developmentally inappropriate demands on children and
      improve the precision of ADHD diagnostic practice and pharmacological treatment.

PMID- 24673584
TI  - Forkhead transcription factor FOXO1 inhibits nuclear factor-kappaB in gastric
      cancer.
AB  - FOXO1, a forkhead box O (FOXO) transcription factor, and nuclear factor-kappaB
      (NF-kappaB) are prognostically significant transcription factors in gastric
      cancer. As their relationship has been inconsistent depending on the cell type,
      we aimed to investigate whether FOXO1 is associated with NF-kappaB p65 (RelA) in
      gastric cancer. Immunohistochemistry was performed on tissue array slides
      containing 298 gastric carcinoma specimens. We found that the cytoplasmic
      expression of pFOXO1, the inactive form of FOXO1, was positively correlated with
      nuclear RelA expression (p = 0.024). In addition, the expressions of pFOXO1 and
      RelA were positively related with cyclin D1 expression (p = 0.014 and p = 0.001,
      respectively) and Ki-67 labeling index (p = 0.025 and p = 0.017, respectively).
      However, they did not show association with the expressions of cyclin E, p53 and
      pRb. Cell culture experiments showed that FOXO1 overexpression by transfection of
      FOXO1 AAA mutant gene suppressed NF-kappaB activation in SNU-484 gastric cancer
      cells. These results suggest that FOXO1 and NF-kappaB are negatively associated
      and that FOXO1 is a negative upstream regulator of NF-kappaB in gastric cancer. 

PMID- 24673586
TI  - EEG delta oscillations index inhibitory control of contextual novelty to both
      irrelevant distracters and relevant task-switch cues.
AB  - Delta oscillations contribute to the human P300 event-related potential evoked by
      oddball targets, although it is unclear whether they index contextual novelty
      (event oddballness, novelty P3, nP3), or target-related processes (event
      targetness, target P3b). To examine this question, the electroencephalogram (EEG)
      was recorded during a cued task-switching version of the Wisconsin card-sorting
      test. Each target card was announced by a tone cueing either to switch or repeat
      the task. Novel sound distracters were interspersed among trials. Time-frequency
      EEG analyses revealed bursts of delta (2-4 Hz) power associated with enhanced nP3
      amplitudes to both task-switch cues and novel distracters-but no association with
      target P3b. These findings indicate that the P300-delta response indexes
      contextual novelty regardless of whether novelty emanates from endogenous (new
      task rules) or exogenous (novel distracters) sources of information. 

PMID- 24673587
TI  - Effects of ketamine on the development of forensically important blowfly
      Chrysomya megacephala (F.) (Diptera: Calliphoridae) and its forensic relevance.
AB  - This study investigated effects of ketamine on the development of Chrysomya
      Megacephala (Diptera: Calliphoridae) at three different temperatures. Larvae of
      the C. Megacephala were exposed to different concentrations of drugs and
      temperatures. The larval lengths, weights, and developmental durations of each
      stage were observed. This study demonstrated that ketamine, low temperature, and
      their synergistic action significantly suppressed the development of C.
      Megacephala (p < 0.001). The time that the larvae in all the treatments achieved
      the maximum length/weight was significantly delayed (p < 0.05), and that resulted
      in prolonged duration of larval and prepupal stages especially at low
      temperature. However, no linear correlations were discovered between ketamine
      concentration and growth rate of larval length/weight.

PMID- 24673588
TI  - A new caryosporan and eimerian (Apicomplexa: Eimeriidae) from green anoles,
      Anolis carolinensis (Sauria: Dactyloidae), from Arkansas and Louisiana, with a
      summary of the coccidia of Dactyloidae.
AB  - Between April 2012 and September 2013, feces from 18 green anoles, Anolis
      carolinensis from Arkansas (n = 14), Louisiana (n = 1), and Oklahoma (n = 3) were
      examined for coccidia. Two species of coccidians were found, including a new
      caryosporan and a new eimerian. Oocysts of Caryospora natchitochesensis n. sp.
      from a single A. carolinensis from Louisiana were subspheroidal to ovoidal with a
      smooth, yellow-to-brown-pigmented, bilayered wall of equal thickness (~0.3-0.7)
      and measured (L * W) 13.1 * 12.3 MUm, with a length/width (L/W) ratio of 1.1. A
      micropyle and oocyst residuum were absent, but a polar granule was present.
      Sporocysts were ovoidal and measured 10.1 * 7.4 MUm, L/W was 1.4. A Stieda body
      (~1.0 MUm) was present, but substieda and parastieda bodies were absent. The
      sporocyst residuum was composed of dispersed granules or globules among
      sporozoites. Oocysts of Eimeria robisoni n. sp. from 1 of 12 (8%) green anoles
      from Arkansas were ellipsoidal with a smooth, unilayered wall (~0.4-0.5) and
      measured (L * W) 14.5 * 10.5 MUm, with L/W ratio of 1.4. A micropyle and oocyst
      residuum were absent, but 1-4 (usually 2) polar granules were present. Sporocysts
      were subspheroidal to ovoidal and measured 5.8 * 4.9 MUm, L/W was 1.2. Stieda,
      substieda, and parastieda bodies were absent. The sporocyst residuum was composed
      of dispersed granules between sporozoites. None of the anoles from Oklahoma was
      found to be passing oocysts. This is the second time an eimerian and a
      caryosporan have been reported from green anoles. A summary of the coccidians of
      lizards of the family Dactyloidae is provided, with special emphasis on the
      Anolis of the United States.

PMID- 24673589
TI  - Microfluidics-assisted diffusion self-assembly: toward the control of the shape
      and size of pectin hydrogel microparticles.
AB  - We demonstrated the generation of pectin hydrogel microparticles having complex
      shapes either by combining the phenomenon of gelation and water diffusion-induced
      self-assembly in microfluidic channels (on-chip) or by the deformation of the
      pregelled droplets outside the channels (off-chip) at a fluid-fluid interface. We
      proved that by tuning the mode of pectin cross-linking (CaCl2 vs CaCO3) and the
      degree of shrinking (water content in the dimethyl carbonate (DMC) organic
      continuous phase) we can control the shape of the final particle. Sphere,
      doughnut, oblate ellipsoid, or mushroom-type morphologies were thus produced,
      demonstrating the ability to control the formation of anisotropic biopolymer
      based hydrogel microparticles using microfluidics. Shape changes were explained
      by the redistribution of calcium ions in combination with the local Peclet number
      experienced by the microdroplets during the on-chip process. Moreover, during the
      off-chip process, the interplay between elastic and viscous forces for
      microdroplets entering the CaCl2-DMC interface caused deformation of the
      pregelled droplets to occur and therefore resulted in the formation of
      microparticles with a mushroom-like morphology. 

PMID- 24673590
TI  - Infrared photodissociation spectroscopy of mass-selected homoleptic cobalt
      carbonyl cluster cations in the gas phase.
AB  - Infrared spectra of mass-selected homoleptic cobalt carbonyl cluster cations
      including dinuclear Co2(CO)8(+) and Co2(CO)9(+), trinuclear Co3(CO)10(+) and
      Co3(CO)11(+), as well as tetranuclear Co4(CO)12(+) are measured via infrared
      photodissociation spectroscopy in the carbonyl stretching frequency region. The
      geometric structures of these complexes are determined by comparison of the
      experimental spectra with those calculated by density functional theory. The
      Co2(CO)8(+) cation is characterized to have a Co-Co bonded structure with Cs
      symmetry involving a bridging CO ligand. The Co2(CO)9(+) cation is determined to
      be a mixture of the CO-tagged Co2(CO)8(+)-CO complex and the Co(CO)5(+)-Co(CO)4
      ion-molecular complex. The Co3(CO)10(+) cation is the coordination-saturated
      trinuclear cluster, which is characterized to have a triangle Co3 core with C2
      symmetry involving two edge-bridging and eight terminal CO ligands. The
      Co3(CO)11(+) cation is a weakly bound complex involving a Co3(CO)10(+) core ion.
      The Co4(CO)12(+) cluster cation is deduced to have a tetrahedral Co4(+) core
      structure with three edge-bridging and nine terminal carbonyls. 

PMID- 24673591
TI  - Fruit cuticle composition of a melting and a nonmelting peach cultivar.
AB  - Although postharvest quality of fruit is greatly affected by cuticle composition,
      structure, and properties, very few published studies have analyzed fruit cuticle
      composition from a postharvest perspective. In this work, the chemical
      composition of waxes and cutin, major cuticular components, was analyzed in fruit
      cuticle samples isolated from a melting ('October Sun') and a nonmelting
      ('Jesca') peach (Prunus persica L. Batsch.) cultivar at harvest and after a
      simulated shelf-life period of 5 days at 20  degrees C. Cutin composition was
      dominated by 18-hydroxyoleic acid, whereas the triterpenoid ursolic and oleanoic
      acids and the alkanes n-tricosane and n-pentacosane were quantitatively prominent
      among the wax compounds identified. Some quantitative differences were found
      between both cultivars for particular compound families and in their postharvest
      modifications. To the best of the authors' knowledge, this is the first study
      characterizing the composition of the cuticle of peach fruit and describing the
      changes therein after harvest. 

PMID- 24673592
TI  - Views of primary care providers regarding the return of genome sequencing
      incidental findings.
AB  - Sequencing of the entire exome or genome is increasingly used in clinical
      practice. Debate continues, however, regarding which incidental findings (IFs)
      should be returned and who should be involved in those decisions. Previous
      empirical research regarding stakeholder attitudes to the return of IFs has
      primarily involved genetics professionals; non-genetics health professionals have
      not been widely surveyed. Given this, a survey regarding return of IFs was
      administered at the Best Practices in Pediatrics Conference following an
      educational presentation on genetics terminology and genetic condition examples.
      A total of 258 participants completed the survey. Of particular note, respondents
      who were positively disposed to sequencing did not always report wanting to learn
      about IFs, even if actionable. This is noteworthy given recent American College
      of Medical Genetics and Genomics guidelines recommending particular actionable IF
      be returned 'without reference to patient preference'. This study's findings are
      important because they provide insight regarding the attitudes to the return of
      genome sequencing results for an important professional group, primary care
      providers. Ultimately, as likely gatekeepers to referrals for this technology,
      their opinions about the test will be key to its successful deployment. 

PMID- 24673593
TI  - A novel nonsense mutation of ADAR1 gene in a Chinese patient with dyschromatosis
      symmetrica hereditaria.

PMID- 24673594
TI  - Overcoming the blood-brain barrier for delivering drugs into the brain by using
      adenosine receptor nanoagonist.
AB  - The extremely low permeability of the blood-brain barrier (BBB) poses the
      greatest impediment in the treatment of central nervous system (CNS) diseases.
      Recent work indicated that BBB permeability can be up-regulated by activating A2A
      adenosine receptor (AR), which temporarily increases intercellular spaces between
      the brain capillary endothelial cells. However, due to transient circulation
      lifetime of adenosine-based agonists, their capability to enhance brain delivery
      of drugs, especially macromolecular drugs, is limited. In this work, a series of
      nanoagonists (NAs) were developed by labeling different copies of A2A AR
      activating ligands on dendrimers. In vitro transendothelial electrical resistance
      measurements demonstrated that the NAs increased permeability of the endothelial
      cell monolayer by compromising the tightness of tight junctions, the key
      structure that restricts the entry of blood-borne molecules into the brain. In
      vivo imaging studies indicated the remarkably up-regulated brain uptake of a
      macromolecular model drug (45 kDa) after intravenous injection of NAs.
      Autoradiographic imaging showed that the BBB opening time-window can be tuned in
      a range of 0.5-2.0 h by the NAs labeled with different numbers of AR-activating
      ligands. By choosing a suitable NA, it is possible to maximize brain drug
      delivery and minimize the uncontrollable BBB leakage by matching the BBB opening
      time-window with the pharmacokinetics of a therapeutic agent. The NA-mediated
      brain drug delivery strategy holds promise for the treatment of CNS diseases with
      improved therapeutic efficiency and reduced side-effects. 

PMID- 24673595
TI  - Synthesis of Cu2O nanospheres decorated with TiO2 nanoislands, their enhanced
      photoactivity and stability under visible light illumination, and their post
      illumination catalytic memory.
AB  - A novel Cu2O/TiO2 composite photocatalyst structure of Cu2O nanospheres decorated
      with TiO2 nanoislands were synthesized by a facile hydrolyzation reaction
      followed by a solvent-thermal process. In this Cu2O/TiO2 composite photocatalyst,
      Cu2O served as the main visible light absorber, while TiO2 nanoislands formed
      heterojunctions of good contact with Cu2O, beneficial to the photoexcited
      electron transfer between them. Their band structure match and inner
      electrostatic field from the p-n heterojunction both favored the transfer of
      photoexcited electrons from Cu2O to TiO2, which effectively separated the
      electron-hole pairs. Photogenerated holes on Cu2O could react with water or
      organic pollutants/microorganisms in water to avoid accumulation on Cu2O because
      of the partial TiO2 nanoislands coverage, which enhanced their stability during
      the photocatalysis process. Their superior photocatalytic performance under
      visible light illumination was demonstrated in both the degradation of methyl
      orange and the disinfection of Escherichia coli bacteria. An interesting post
      illumination catalytic memory was also observed for this composite photocatalyst
      as demonstrated in the disinfection of Escherichia coli bacteria in the dark
      after the visible light was shut off, which could be attributed to the transfer
      of photoexcited electrons from Cu2O to TiO2 and their trapping on TiO2 under
      visible light illumination, and their release in the dark after the visible light
      was shut off. 

PMID- 24673597
TI  - Using incident response trees as a tool for risk management of online financial
      services.
AB  - The article introduces the use of probabilistic risk assessment for modeling the
      incident response process of online financial services. The main contribution is
      the creation of incident response trees, using event tree analysis, which
      provides us with a visual tool and a systematic way to estimate the probability
      of a successful incident response process against the currently known risk
      landscape, making it possible to measure the balance between front-end and back
      end security measures. The model is presented using an illustrative example, and
      is then applied to the incident response process of a Swedish bank. Access to
      relevant data is verified and the applicability and usability of the proposed
      model is verified using one year of historical data. Potential advantages and
      possible shortcomings are discussed, referring to both the design phase and the
      operational phase, and future work is presented. 

PMID- 24673596
TI  - Hepatic gene delivery system electrostatically assembled with glycyrrhizin.
AB  - In this study, a novel liver-targeted gene delivery vector was developed by
      electrostatically coating the cationic complex of pDNA and polyethylenimine (PEI)
      with glycyrrhizin (GL). The ternary complex, pDNA/PEI/GL, had approximately 100
      nm stable particles with a negative charge surface. pDNA/PEI/GL showed high gene
      expression comparable to that of the complex of pDNA and PEI (pDNA/PEI) in human
      hepatoma cell line HepG2 without cytotoxicity and agglutination. After
      intravenous injection of pDNA/PEI/GL into mice, the highest gene expression was
      observed in the liver. pDNA/PEI/GL showed significantly higher gene expression in
      parenchymal cells than in nonparenchymal cells. On the basis of these results, we
      evaluated the pharmacological activity of the ternary complex including the pDNA
      encoding insulin (pCMV-Ins). The pCMV-Ins/PEI/GL decreased blood glucose
      concentrations 24 h after its intravenous administration to mice. The ternary
      complex of pDNA, PEI, and GL may be a promising liver-targeted gene vector. 

PMID- 24673598
TI  - Inhibitory control and delay aversion in unaffected preschoolers with a positive
      family history of attention deficit hyperactivity disorder.
AB  - BACKGROUND: From current theories on the etiology of attention deficit
      hyperactivity disorder (ADHD), it can be inferred that delay aversion (DA) and
      deficits in inhibitory control (IC) constitute basic deficits or endophenotypes
      of the disorder that already occur in the preschool period. This implies an
      occurrence of the characteristics in unaffected preschoolers with a positive
      family history of ADHD. Thus, it is hypothesized that preschoolers who are not
      affected by ADHD but who have first-degree relatives who suffer, or have
      suffered, from ADHD show deficits in IC and heightened DA in comparison to
      preschoolers from the general population. METHODS: Thirty unaffected preschoolers
      with a positive family history of ADHD were compared with 30 control children
      matched with respect to age in months, gender, intelligence, and maternal
      education level. The groups also did not differ in terms of maternal depressive
      symptoms and the number of psychosocial family risks. A set of age-appropriate
      neuropsychological tasks on executive IC (e.g. Puppet Says, Day-Night, relying on
      Go-NoGo and interference paradigms) and DA (e.g. Snack Delay, Gift Wrap, relying
      on delay of gratification paradigm) was conducted. RESULTS: Unaffected
      preschoolers showed significantly higher DA than control children (t(29) = -2.57,
      p < .008). The result did not change when subclinical ADHD symptoms and symptoms
      of oppositional defiant disorder were controlled for (F(1,29) = 5.21, p < .031).
      Differences in IC did not reach statistical significance. CONCLUSION: The results
      are compatible with the assumption that DA constitutes a familial vulnerability
      marker that can be validly assessed in the preschool period. As this is the first
      study to address this issue in preschoolers, more research is needed to confirm
      and further analyze the significance of DA assessments specifically at this
      developmental stage.

PMID- 24673600
TI  - Predictors of family and marital functioning at early postpartum.
AB  - AIM: To examine the predictive role of family sense of coherence, social support
      and stress during pregnancy and their changes from pregnancy to postpartum on
      family and marital functioning at 6 weeks postpartum. BACKGROUND: Family sense of
      coherence plays a significant role in promoting positive family and marital
      functioning, which is crucial to the child's well-being. However, studies that
      evaluate the predictive role of family sense of coherence on family and marital
      functioning during parental transition are limited. DESIGN: The study used a
      longitudinal design. METHODS: Chinese childbearing couples (n = 202) completed
      assessments of family sense of coherence, stress, social support, and family and
      marital functioning during pregnancy and at 6 weeks postpartum between January
      2011-May 2012. RESULTS/FINDINGS: Mothers with a stronger family sense of
      coherence, greater social support and less stress during pregnancy experienced
      less decline in family and marital functioning at 6 weeks postpartum, while
      fathers with a higher prenatal family sense of coherence and family and marital
      functioning also experienced less such decline. CONCLUSION: Couple-based
      interventions should be initiated early during pregnancy by strengthening family
      sense of coherence and social support to promote positive family functioning.

PMID- 24673599
TI  - Priapism following continuous thoracic epidural anaesthesia: emergency or a
      benign condition?
AB  - Priapism is a rare complication of epidural anaesthesia, and the pathophysiology
      is poorly understood. In general, 95% of all priapism episodes are ischemic
      because of decreased penile blood flow, and therefore requires immediate
      treatment. A case is reported of a 45-year-old male patient in which a clear
      relation is demonstrated between continuous thoracic epidural analgesia and
      priapism after transabdominal nephrectomy. The level of epidural anaesthesia
      supports the theory that the erection is a consequence of increased penile blood
      flow, thus a relatively harmless condition. However, confirmation by serial
      cavernous blood gas analysis or colour duplex ultrasonography is mandatory. Until
      this hypothesis is confirmed, termination of epidural infusion is advised as a
      primary treatment.

PMID- 24673601
TI  - GLCCI1 variant accelerates pulmonary function decline in patients with asthma
      receiving inhaled corticosteroids.
AB  - BACKGROUND: In steroid-naive patients with asthma, several gene variants are
      associated with a short-term response to inhaled corticosteroid (ICS) treatment;
      this has mostly been observed in Caucasians. However, not many studies have been
      conducted for other ethnicities. Here, we aimed to determine the relationship
      between the annual decline in forced expiratory flow volume in one second (FEV1 )
      and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in
      Japanese patients with asthma receiving long-term ICS treatment, taking into
      account the effect of high serum periostin levels, a known association factor of
      pulmonary function decline and a marker of refractory eosinophilic/Th2
      inflammation. METHODS: In this study, 224 patients with asthma receiving ICS
      treatment for at least 4 years were enrolled. The effects of single-nucleotide
      polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T
      gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS:
      Besides the known contributing factors, that is, the most intensive treatment
      step, ex-smoking, and high serum periostin levels (>=95 ng/ml), the GG genotype
      of GLCCI1 rs37973, and not other SNPs, was independently associated with a
      decline in FEV1 of 30 ml/year or greater. When patients were stratified according
      to their serum periostin levels, the GG genotype of rs37973 was significantly
      associated with blood eosinophilia (>=250/MUl) in the high serum periostin group.
      CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in
      Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may
      be associated with response to ICS across ethnicities.

PMID- 24673603
TI  - Reported outcomes of lower limb orthopaedic surgery in children and adolescents
      with cerebral palsy: a mapping review.
AB  - AIM: Lower limb surgery is often performed in ambulatory children with cerebral
      palsy (CP) to improve walking ability. This mapping review reports on outcome
      measures used in the published literature to assess surgical results, determine
      range and frequency of use, and map each measure to the International
      Classification of Functioning, Disability and Health. METHOD: A mapped review of
      literature published between 1990 and 2011 was carried out to identify papers
      reporting the outcomes of lower limb orthopaedic surgery in ambulatory children
      with CP, aged 0 to 20 years. RESULTS: A total of 229 published papers met the
      inclusion criteria. Thirty-two outcome measures with known psychometric
      properties were reported in the 229 papers. Twenty measures assess impairments in
      body structure and function and were used in 91% of studies. Ten measures assess
      restrictions in activity and participation and were used in 9% of papers. Two
      measures assessed quality of life. Since 1997, 29% of papers have used the Gross
      Motor Function Classification System to describe participants. INTERPRETATION:
      The body of literature evaluating outcomes of lower limb orthopaedic surgery in
      CP is small but increasing. There is a need to develop a suite of outcome
      measures that better reflect outcomes across the International Classification of
      Functioning, Disability and Health, including activity and participation.

PMID- 24673602
TI  - Melanoma cell lysate induces CCR7 expression and in vivo migration to draining
      lymph nodes of therapeutic human dendritic cells.
AB  - We have previously reported a novel method for the production of tumour-antigen
      presenting cells (referred to as TAPCells) that are currently being used in
      cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as
      TRIMEL) as an antigen provider and activation factor. It was recently
      demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune
      responses resulting in improved long-term survival of stage IV melanoma patients.
      Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is
      an important requirement for an effective anti-tumour immunization. This
      mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7),
      which is up-regulated on mature DCs. Using flow cytometry and
      immunohistochemistry, we investigated if TRIMEL was capable of inducing the
      expression of the CCR7 on TAPCells and enhancing their migration in vitro, as
      well as their in vivo relocation to lymph nodes in an ectopic xenograft animal
      model. Our results confirmed that TRIMEL induces a phenotypic maturation and
      increases the expression of surface CCR7 on melanoma patient-derived DCs, and
      also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays
      showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating
      specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated
      that TAPCells could migrate in vivo from the injection site into the draining
      lymph nodes. This work contributes to an increased understanding of the biology
      of DCs produced ex vivo allowing the design of new strategies for effective DC
      based vaccines for treating aggressive melanomas. 

PMID- 24673604
TI  - Rab27A regulates exosome secretion from lung adenocarcinoma cells A549:
      involvement of EPI64.
AB  - Exosomes are small membrane vesicles secreted into the extracellular compartment
      by exocytosis. The unique composition of exosomes can be transported to other
      cells which allow cells to exert biological functions at distant sites. However,
      in lung cancer, the regulation of exosome secretion was poorly understood. In
      this study, we employed human lung adenocarcinoma A549 cells to determine the
      exosome secretion and involved regulation mechanism. We found that Rab27A was
      expressed in A549 cells and the reduction of Rab27A by Rab27A-specific shRNA
      could significantly decrease the secretion of exosome by A549 cells. EPI64, a
      candidate GAP that is specific for Rab27, was also detected in A549 cells. By
      pull-down assay, we found that EPI64 participated in the exosome secretion of
      A549 cells by acting as a specific GAP for Rab27A, not Rab27B. Overexpression of
      EPI64 enhanced exosome secretion. Taken together, in A549 cells, EPI64 could
      regulate the exosome secretion by functioning as a GAP specific for Rab27A. 

PMID- 24673605
TI  - Effect of lymph node dissection on the outcomes of upper tract urothelial
      carcinomas: a meta-analysis.
AB  - A systematic search was conducted in PubMed, Cochrane Library. 6032 patients were
      included. There was no significant difference in survival between LND and NLND
      (non-lymph node dissection) among the patients. However, the patients in the LND
      group had more advanced tumour stages and grades (p < 0.001). In addition, among
      the muscle-invasive patients, LND demonstrated remarkable CSS improvement
      compared with NLND (HR: 2.19; 95% CI: 1.26-3.80; p = 0.005). Moreover, subgroup
      analyses found that patients with muscle-invasive UTUC had better CSS (HR: 1.22;
      95% CI: 1.02-1.45; p < 0.001) than those patients with pN0 compared to pNx
      (NLND). In terms of RFS, the results showed no difference in the survival rates
      between pN0 and pNx patients in the subgroup of patients with muscle-invasive
      UTUC (HR: 1.40; 95% CI: 0.84-2.23; p = 0.19). Our meta-analysis supports that LND
      may prolong the CSS and RFS of UTUC, especially for patients with muscle-invasive
      UTUC.

PMID- 24673606
TI  - The neural fate of neutral information in emotion-enhanced memory.
AB  - In this study, we report evidence that neural activity reflecting the encoding of
      emotionally neutral information in memory is reduced when neutral and emotional
      stimuli are intermixed during encoding. Specifically, participants studied
      emotional and neutral pictures organized in mixed lists (in which emotional and
      neutral pictures were intermixed) or in pure lists (only-neutral or only
      emotional pictures) and performed a recall test. To estimate encoding efficiency,
      we used the Dm effect, measured with event-related potentials. Recall for neutral
      items was lower in mixed compared to pure lists and posterior Dm activity for
      neutral items was reduced in mixed lists, whereas it remained robust in pure
      lists. These findings might be caused by an asymmetrical competition for
      attentional and working memory resources between emotional and neutral
      information, which could be a major determinant of emotional memory effects. 

PMID- 24673607
TI  - Comparative study on the properties of hydration water of Na- and K-halide ions
      by Raman OH/OD-stretching spectroscopy and dielectric relaxation data.
AB  - Properties of hypermobile water (HMW) were studied by Raman OH-stretching
      spectroscopy. Hydration water properties measured by Raman OH-stretching spectra
      of NaX/KX (X: Cl, Br, I) solutions (0.05-0.2 M) were comparatively analyzed with
      the data by dielectric relaxation spectroscopy (DRS), NMR, and statistical
      mechanical studies. The Raman OH-stretching spectra were well-fitted with linear
      combinations of the spectra of pure water both at the same and the higher
      temperatures. The fitting analysis determined the "structure temperature" Tstr
      and mole fraction of the high Tstr water region, giving the hydration number
      Nhyd, for each electrolyte solution. The determined Tstr was much higher than the
      solution temperature of 293 K for each tested salt and was higher for larger
      halide ions, consistent with commonly known "structure-breaking" order Cl < Br <
      I. No significant differences in Nhyd were observed between NaX and KX and among
      even halide ion species within the experimental errors. Measured Nhyd values of
      25-27 were much greater than the reported numbers by NMR chemical shift and (17)O
      NMR relaxation studies and comparable to the numbers of hypermobile water
      reported in the previous DRS studies. The results indicated that the hydration
      region around NaX or KX measured by the present Raman study was nearly overlapped
      with the region of HMW by DRS. It was also suggested that differences in the ion
      size effects on Tstr and the DR frequency resulted from the sensitivity
      difference to long-range many-body interactions among water molecules. High
      structure-temperature regions were also detected by the analysis of OH-stretching
      and OD-stretching bands for 0.2 M NaI in H2O/D2O mixed solvent of 50 mol %, and
      we found that both OH-stretching and OD-stretching bands have almost equivalent
      Tstr ~ 330 K and mole fractions with each other. 

PMID- 24673608
TI  - Short- and long-term cure rates of short-duration trimethoprim-sulfamethoxazole
      treatment in female dogs with uncomplicated bacterial cystitis.
AB  - BACKGROUND: Long-duration beta-lactam antibiotics are used for empirical
      treatment in female dogs with uncomplicated bacterial cystitis. However, women
      with bacterial cystitis are treated with short-duration potentiated sulfonamides
      because longer courses of beta-lactams result in lower cure and higher recurrence
      rates. HYPOTHESIS/OBJECTIVES: Short-duration potentiated sulfonamide treatment is
      more efficacious than long-duration beta-lactam treatment in achieving clinical
      and microbiological cures in female dogs with uncomplicated bacterial cystitis.
      ANIMALS: Thirty-eight client-owned female dogs. METHODS: Randomized, double
      blinded, placebo-controlled clinical trial. Dogs were treated with TMP-SMX (15
      mg/kg PO q12h for 3 days followed by a placebo capsule PO q12h for 7 days; Group
      SDS; n = 20) or cephalexin (20 mg/kg PO q12h for 10 days; Group LDBL; n = 18).
      Dogs were monitored for clinical and microbiological cure during treatment and at
      short- and long-term follow-up. RESULTS: No statistically significant differences
      were found between treatment groups in clinical cure rates after 3 days of
      treatment (89% SDS, 94% LDBL; P = 1.00) and 4 days (85% SDS, 72% LDBL; P = .44)
      or >30 days (50% SDS, 65% LDBL; P = .50) after conclusion of treatment or in
      microbiological cure rates 4 days (59% SDS, 36% LDBL; P = .44) or >30 days (44%
      SDS, 20% LDBL; P = .40) after conclusion of treatment. CONCLUSIONS AND CLINICAL
      IMPORTANCE: We did not identify a difference in cure rates between short-duration
      sulfonamide and long-duration beta-lactam treatments in female dogs with
      uncomplicated cystitis. Long-term cure rates in both treatment groups were low.
      In some female dogs, "uncomplicated" bacterial cystitis may be more complicated
      than previously recognized.

PMID- 24673609
TI  - Open-label, single-arm, phase II study of enzastaurin in patients with follicular
      lymphoma.
AB  - This open-label, phase II study investigated whether enzastaurin, a protein
      kinase C-beta (PKCbeta) inhibitor, had activity in patients with grade 1 or 2
      follicular lymphoma (FL). Adults with grade 1 or 2 FL who had no more than one
      prior treatment received oral enzastaurin continuously for up to 3 years. Of the
      66 patients who received enzastaurin, 53 were evaluable for response. Overall
      response rate (ORR, primary efficacy endpoint) was 26.4% (3.8% complete
      response). Median (95% confidence interval) progression-free survival, time to
      response, and duration of response were 18.1 (11.5-28.3), 4.9 (2.8-8.1), and 22.3
      (8.8-not applicable) months, respectively. In patients with tumour tissue
      available for biomarker analysis, ORRs in low versus high PKCbeta2 expression
      groups were 41.7% and 8.3%, respectively (P = 0.041). The most common, mainly low
      grade drug-related adverse events were fatigue (25.8%), diarrhoea (25.8%), nausea
      (18.2%), and chromaturia (18.2%). Four (6.1%) patients had Grade 3 toxicity and
      one (1.5%) patient had Grade 4 toxicity. Enzastaurin demonstrated limited
      clinical activity in grade 1 or 2 FL. Patients with low PKCbeta2 expression in
      tumours had higher ORR than those with high PKCbeta2 expression. Enzastaurin was
      well tolerated with mostly grade 1 or 2 toxicities. Further studies may be
      warranted in select patient populations.

PMID- 24673610
TI  - Two-photon fluorescence imaging and bimodal phototherapy of epidermal cancer
      cells with biocompatible self-assembled polymer nanoparticles.
AB  - We have developed herein an engineered polymer-based nanoplatform showing the
      convergence of two-photon fluorescence imaging and bimodal phototherapeutic
      activity in a single nanostructure. It was achieved through the appropriate
      choice of three different components: a beta-cyclodextrin-based polymer acting as
      a suitable carrier, a zinc phthalocyanine emitting red fluorescence
      simultaneously as being a singlet oxygen ((1)O2) photosensitizer, and a tailored
      nitroaniline derivative, functioning as a nitric oxide (NO) photodonor. The self
      assembly of these components results in photoactivable nanoparticles,
      approximately 35 nm in diameter, coencapsulating a multifunctional cargo, which
      can be delivered to carcinoma cells. The combination of steady-state and time
      resolved spectroscopic and photochemical techniques shows that the two
      photoresponsive guests do not interfere with each other while being enclosed in
      their supramolecular container and can thus be operated in parallel under control
      of light stimuli. Specifically, two-photon fluorescence microscopy allows mapping
      of the nanoassembly, here applied to epidermal cancer cells. By detecting the red
      emission from the phthalocyanine fluorophore it was also possible to investigate
      the tissue distribution after topical delivery onto human skin ex vivo.
      Irradiation of the nanoassembly with visible light triggers the simultaneous
      delivery of cytotoxic (1)O2 and NO, resulting in an amplified cell photomortality
      due to a combinatory effect of the two cytotoxic agents. The potential of dual
      therapeutic photodynamic action and two-photon fluorescence imaging capability in
      a single nanostructure make this system an appealing candidate for further
      studies in biomedical research. 

PMID- 24673611
TI  - QbD-based systematic development of novel optimized solid self-nanoemulsifying
      drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical
      performance.
AB  - Of late, solid self-nanoemulsifying drug delivery systems (S-SNEDDS) have been
      extensively sought-after owing to their superior portability, drug loading,
      stability and patient compliance. The current studies, therefore, entail
      systematic development, optimization and evaluation (in vitro, in situ and in
      vivo) of the solid formulations of (SNEDDS) lovastatin employing rational quality
      by design (QbD)-based approach of formulation by design (FbD). The patient
      centric quality target product profile (QTPP) and critical quality attributes
      (CQAs) were earmarked. Preformulation studies along with initial risk assessment
      facilitated the selection of lipid (i.e. Capmul MCM), surfactant (i.e. Nikkol HCO
      50) and co-surfactant (i.e. Lutrol F127) as CMAs for formulation of S-SNEDDS. A
      face-centered cubic design (FCCD) was employed for optimization using Nikkol
      HCO50 (X1) and Lutrol-F127 (X2), evaluating CQAs like globule size, liquefaction
      time, emulsification time, MDT, dissolution efficiency and permeation parameter.
      The design space was generated using apt mathematical models, and the optimum
      formulation was located, followed by validation of the FbD methodology. In situ
      SPIP and in vivo pharmacodynamic studies on the optimized formulation carried out
      in unisex Wistar rats, corroborated superior drug absorption and enhanced
      pharmacodynamic potential in regulating serum lipid levels. In a nutshell, the
      present studies report successful QbD-oriented development of novel oral S-SNEDDS
      of lovastatin with distinctly improved biopharmaceutical performance. 

PMID- 24673612
TI  - Lichen striatus in a mother and son.

PMID- 24673613
TI  - In situ mechanical characterization of the cell nucleus by atomic force
      microscopy.
AB  - The study of nuclear mechanical properties can provide insights into nuclear
      dynamics and its role in cellular mechanotransduction. While several methods have
      been developed to characterize nuclear mechanical properties, direct
      intracellular probing of the nucleus in situ is challenging. Here, a modified AFM
      (atomic force microscopy) needle penetration technique is demonstrated to
      mechanically characterize cell nuclei in situ. Cytoplasmic and nuclear stiffness
      were determined based on two different segments on the AFM indentation curves and
      were correlated with simultaneous confocal Z-stack microscopy reconstructions. On
      the basis of direct intracellular measurement, we show that the isolated nuclei
      from fibroblast-like cells exhibited significantly lower Young's moduli than
      intact nuclei in situ. We also show that there is in situ nucleus softening in
      the highly metastatic bladder cancer cell line T24 when compared to its less
      metastatic counterpart RT4. This technique has potential to become a reliable
      quantitative measurement tool for intracellular mechanics studies. 

PMID- 24673614
TI  - Development and validation of the Diabetes Medication System Rating Questionnaire
      Short Form.
AB  - AIMS: To develop and validate a short form of the 54-item Diabetes Medication
      System Rating Questionnaire that maintains the domains and performance
      characteristics of the long-form questionnaire. METHODS: Data from the Diabetes
      Medication System Rating Questionnaire validation study were analysed to select
      items representing the nine scales (convenience, negative events, interference,
      self-monitoring of blood glucose burden, efficacy, social burden, psychological
      well-being, treatment satisfaction and treatment preference). The resulting 20
      item Diabetes Medication System Rating Questionnaire Short-Form was administered
      online, with validated criterion measures of treatment satisfaction and
      medication adherence, with a retest within 2 weeks. Participants were US adults
      (N = 413) with Type 2 diabetes using oral agents alone; insulin by syringe and/or
      pen with or without oral agents; or glucagon-like peptide-1 agents. Most
      participants (82%) completed the retest. RESULTS: The median inter-item agreement
      of scales was 0.76 and the total composite (mean of all items except treatment
      preference) was 0.88. The median test-retest reliability of scales was 0.86, and
      of the total composite was 0.95. All statistically significant correlations
      between Diabetes Medication System Rating Questionnaire Short-Form scales and
      criterion measures of treatment satisfaction and adherence were in the expected
      direction. The median correlation of the Diabetes Medication System Rating
      Questionnaire Short-Form with corresponding criterion measures of treatment
      satisfaction was 0.59; the mean correlation of the same Diabetes Medication
      System Rating Questionnaire Short-Form measures with adherence was 0.42. The
      Diabetes Medication System Rating Questionnaire Short-Form scales were more
      powerful predictors of adherence than were the criterion measures of treatment
      satisfaction. The Diabetes Medication System Rating Questionnaire Short-Form
      scales differentiated between those taking different medications and between
      those using different insulin delivery devices. CONCLUSIONS: This study suggests
      that the Diabetes Medication System Rating Questionnaire Short-Form provides a
      comprehensive set of measures with acceptable reliability and validity and a
      reduced burden of administration.

PMID- 24673615
TI  - Adult age differences in subjective and objective measures of strategy use on a
      sequentially cued prediction task.
AB  - Differences in strategy use are thought to underlie age-related performance
      deficits on many learning and decision-making tasks. Recently, age-related
      differences in learning to make predictions were reported on the Triplets
      Prediction Task (TPT). Notably, deficits appeared early in training and continued
      with experience. To assess if age differences were due to early strategy use,
      neural networks were used to objectively assess the strategies implemented by
      participants during Session 1. Then, the relationship between these strategies
      and performance was examined. Results revealed that older adults were more likely
      to implement a disadvantageous strategy early in learning, and this led to poorer
      task performance. Importantly, the relationship between age and task performance
      was partially mediated by early strategy use, suggesting that early strategy
      selection played a role in the lower quality of predictions in older adults.

PMID- 24673616
TI  - Role of sleep apnea and continuous positive airway pressure therapy in the
      incidence of stroke or coronary heart disease in women.
AB  - RATIONALE: It is unknown whether obstructive sleep apnea (OSA) may be a risk
      factor for incident cardiovascular events in women. OBJECTIVES: We sought to
      investigate whether OSA increases the incidence of a composite of stroke or
      coronary heart disease (CHD) in women, and the role of continuous positive airway
      pressure (CPAP) treatment on this association. METHODS: This was a prospective,
      observational study conducted in two Spanish teaching hospitals between 1998 and
      2007. Consecutive women referred for suspected OSA and free of previous stroke
      and CHD were analyzed. Women with an apnea-hypopnea index (AHI) less than 10
      comprised the control group, and those with an AHI greater than or equal to 10
      were diagnosed with OSA and classified as CPAP-treated (adherence >= 4 h/d) or
      untreated (adherence < 4 h/d or not prescribed). The follow-up ended in December
      2010. MEASUREMENTS AND MAIN RESULTS: A total of 967 women were studied (median
      follow-up, 6.8 yr; interquartile range, 5.2-8.2). The untreated OSA group showed
      a greater incidence rate of the composite outcome than the control group (2.19
      vs. 0.54 per 100 person-years; P < 0.0005). Compared with the control group, the
      fully adjusted hazard ratios for the composite outcome incidence were 2.76 (95%
      confidence interval [CI], 1.35-5.62) for the untreated OSA group, and 0.91 (95%
      CI, 0.43-1.95) for the CPAP-treated group. When the type of cardiovascular event
      was separately assessed, untreated OSA showed a stronger association with
      incident stroke (adjusted hazard ratio, 6.44; 95% CI, 1.46-28.3) than with CHD
      (adjusted hazard ratio, 1.77; 95% CI, 0.76-4.09). CONCLUSIONS: In women,
      untreated OSA is associated with increased incidence of serious cardiovascular
      outcomes, particularly incident stroke. Adequate CPAP treatment seems to reduce
      this risk.

PMID- 24673617
TI  - 'Short-term treatment with methotrexate does not affect microvascular endothelial
      function in patients with psoriasis'.
AB  - BACKGROUND: Psoriasis is associated with increased risk of cardiovascular disease
      (CVD), possibly due to chronic low-grade systemic inflammation. Systemic anti
      inflammatory treatment might reduce the risk of CVD. OBJECTIVE: Our aim was to
      investigate if short-term treatment with methotrexate influences microvascular
      endothelial function (MEF), an early surrogate marker of atherosclerosis, in
      patients with psoriasis. METHODS: We prospectively studied a hospital cohort of
      patients with psoriasis. Measurements of MEF were performed with the Endo
      PAT2000(c) device at baseline and after 8-10 weeks of treatment with
      methotrexate. At the same time points, we recorded anamnestic information,
      measured body mass index (BMI), waist and hip circumferences and blood pressure,
      and drew blood samples (lipid profile, HbA1 and hs-CRP). Psoriasis severity was
      evaluated by psoriasis area and severity index (PASI) and the dermatology life
      quality index (DLQI). RESULTS: A total of 32 patients with psoriasis were
      included. Median age was 46 (range 18-82) years, and 50% were men. Twenty-seven
      patients completed the study. After 8-10 weeks, median PASI had decreased
      significantly by 6.2 (from 9.8 to 3.6), and DLQI had decreased by 7 (from 9 to
      2). No significant changes were observed in MEF, expressed by reactive hyperaemia
      index and augmentation index. Also, we saw no significant changes in BMI, waist
      hip ratio, blood pressure and blood samples. CONCLUSION: Short-term treatment
      with methotrexate did not affect MEF in patients with psoriasis. Further studies
      are warranted.

PMID- 24673618
TI  - Understanding household preferences for hurricane risk mitigation information:
      evidence from survey responses.
AB  - Risk information is critical to adopting mitigation measures, and seeking risk
      information is influenced by a variety of factors. An essential component of the
      recently adopted My Safe Florida Home (MSFH) program by the State of Florida is
      to provide homeowners with pertinent risk information to facilitate hurricane
      risk mitigation activities. We develop an analytical framework to understand
      household preferences for hurricane risk mitigation information through allowing
      an intensive home inspection. An empirical analysis is used to identify major
      drivers of household preferences to receive personalized information regarding
      recommended hurricane risk mitigation measures. A variety of empirical
      specifications show that households with home insurance, prior experience with
      damages, and with a higher sense of vulnerability to be affected by hurricanes
      are more likely to allow inspection to seek information. However, households with
      more members living in the home and households who live in manufactured/mobile
      homes are less likely to allow inspection. While findings imply MSFH program's
      ability to link incentives offered by private and public agencies in promoting
      mitigation, households that face a disproportionately higher level of risk can
      get priority to make the program more effective. 

PMID- 24673619
TI  - Terrestrial edible land snails as vectors for geographic dissemination of
      Brachylaima species.
AB  - Cornu aspersum (= syn. Helix aspersa ) snails imported into NE Spain from Algeria
      and South Africa, and intended for human consumption via sale in public markets,
      were analyzed to assess their contribution to geographic dissemination of
      Brachylaima species. Prevalence and viability studies of metacercariae were
      performed on Algerian and South African Brachylaima adults. Morphometric studies
      were performed by measuring 16 variables in metacercariae and 18 variables in
      adults. Principal component analyses (PCA) were performed to assess the
      contribution of each variable in the separation of the different groups. A MANOVA
      test performed on morphometric data from Brachylaima llobregatensis and
      Brachylaima mascomai Algerian and South African adults, revealed a significant
      multivariate main effect (P < 0.001) and univariate effects in 13 variables (P <=
      0.001). Pairwise comparisons revealed significant differences in 13 variables
      between B. mascomai and Algerian adults, as opposed to 3 variables (testis I
      width, testis II width, and egg width) when compared with B. llobregatensis.
      South African adults had significant differences in 5 variables (body length,
      oral sucker length, oral sucker width, egg length, and egg width) when compared
      with B. llobregatensis, as opposed to 1 variable (testis II width) when compared
      with B. mascomai. Results from PCA showed 2 different groups: B.
      llobregatensis/Algerian adults (overlapped) and B. mascomai/South African adults
      (overlapped). Imported edible C. aspersum specimens can contribute significantly
      to the geographic spread of Brachylaima species by harboring infective
      metacercariae which could easily infect animals, given their heteroxenous
      character. Brachylaima llobregatensis has previously been detected in NE Spain
      only, and now this species appears to be parasitizing C. aspersum in Algeria
      (North Africa). This geographic dispersion could be favored by commerce in
      terrestrial snails such as C. aspersum. 

PMID- 24673620
TI  - Assessing Nurse Anaesthetists' Non-Technical Skills in the operating room.
AB  - BACKGROUND: Incident reporting and fieldwork in operating rooms have shown that
      some of the errors that arise in anaesthesia relate to inadequate use of non
      technical skills. To provide a tool for training and feedback on nurse
      anaesthetists' non-technical skills, this study aimed to adapt the Anaesthetists'
      Non-Technical Skills (ANTS) as a behavioural marker system for the formative
      assessment of nurse anaesthetists' non-technical skills in the operating room.
      METHODS: A qualitative approach with focus group interviews was used to identify
      the non-technical skills of nurse anaesthetists in the operating room. The
      interview data were transcribed verbatim. Directed content analysis was used to
      code and sort data deductively into the ANTS categories: task management, team
      working, situation awareness and decision making. The prototype named Nurse
      Anaesthetists' Non-Technical Skills (N-ANTS) was presented and discussed in a
      group of subject matter experts to ensure face validity. RESULTS: The N-ANTS
      system consists of the same four categories as ANTS and 15 underlying elements.
      Three to five good and poor behavioural markers for each element were identified.
      The headings and definitions of the categories and elements were adjusted to
      encompass the behavioural markers in N-ANTS. The differences that emerged mainly
      reflected statements regarding the establishment of role, competence, and task
      delegation. CONCLUSION: A behavioural marker system, N-ANTS, for nurse
      anaesthetists was adapted from a behavioural marker system, ANTS, for
      anaesthesiologists.

PMID- 24673621
TI  - Task motivation influences alpha suppression following errors.
AB  - The goal of the present research is to examine the influence of motivation on a
      novel error-related neural marker, error-related alpha suppression (ERAS).
      Participants completed an attentionally demanding flanker task under conditions
      that emphasized either speed or accuracy or under conditions that manipulated the
      monetary value of errors. Conditions in which errors had greater motivational
      value produced greater ERAS, that is, greater alpha suppression following errors
      compared to correct trials. A second study found that a manipulation of task
      difficulty did not affect ERAS. Together, the results confirm that ERAS is both a
      robust phenomenon and one that is sensitive to motivational factors. 

PMID- 24673622
TI  - Codelivery of doxorubicin and paclitaxel by cross-linked multilamellar liposome
      enables synergistic antitumor activity.
AB  - Combining chemotherapeutics is a promising method of improving cancer treatment;
      however, the clinical success of combination therapy is limited by the distinct
      pharmacokinetics of combined drugs, which leads to nonuniform distribution. In
      this study, we report a new robust approach to load two drugs with different
      hydrophilicities into a single cross-linked multilamellar liposomal vesicle
      (cMLV) to precisely control the drug ratio that reaches the tumor in vivo. The
      stability of cMLVs improves the loading efficiency and sustained release of
      doxorubicin (Dox) and paclitaxel (PTX), maximizing the combined therapeutic
      effect and minimizing the systemic toxicity. Furthermore, we show that the cMLV
      formulation maintains specific drug ratios in vivo for over 24 h, enabling the
      ratio-dependent combination synergy seen in vitro to translate to in vivo
      antitumor activity and giving us control over another parameter important to
      combination therapy. This combinatorial delivery system may provide a new
      strategy for synergistic delivery of multiple chemotherapeutics with a
      ratiometric control over encapsulated drugs to treat cancer and other diseases. 

PMID- 24673623
TI  - Spontaneous rupture of the gall bladder: an unusual forensic diagnosis.
AB  - Peritonitis secondary to spontaneous rupture/perforation of the gall bladder is a
      rare condition overall and is even less common in the forensic population. We
      report the case of a middle-aged man who died from generalized peritonitis from
      gall bladder perforation due to acute acalculous cholecystitis. This condition
      usually occurs in critical patients with systemic illness, and although the exact
      pathogenesis remains unclear, the development of acalculous cholecystitis appears
      to be multifactorial. Antemortem diagnosis is reliant upon clinical presentation,
      laboratory data, and radiologic studies. Surgery and appropriate antibiotics are
      mainstays of treatment; however, there is an emerging role for minimally invasive
      procedures. Histopathologic features show significant overlap with the calculous
      type. Although increasing numbers of acalculous cholecystitis have been diagnosed
      in the critically ill, the fatal presentation of a perforated gall bladder
      following an undiagnosed case of acute acalculous cholecystitis is unusual in a
      nonhospitalized and ambulatory man. 

PMID- 24673625
TI  - Does epilepsy in childhood affect cognitive development?

PMID- 24673624
TI  - C-reactive protein is essential for innate resistance to pneumococcal infection.
AB  - No deficiency of human C-reactive protein (CRP), or even structural polymorphism
      of the protein, has yet been reported so its physiological role is not known.
      Here we show for the first time that CRP-deficient mice are remarkably
      susceptible to Streptococcus pneumoniae infection and are protected by
      reconstitution with isolated pure human CRP, or by anti-pneumococcal antibodies.
      Autologous mouse CRP is evidently essential for innate resistance to pneumococcal
      infection before antibodies are produced. Our findings are consistent with the
      significant association between clinical pneumococcal infection and non-coding
      human CRP gene polymorphisms which affect CRP expression. Deficiency or loss of
      function variation in CRP may therefore be lethal at the first early-life
      encounter with this ubiquitous virulent pathogen, explaining the invariant
      presence and structure of CRP in human adults. 

PMID- 24673626
TI  - Changes in nurses' views and practices concerning nurse prescribing between 2006
      and 2012: results from two national surveys.
AB  - AIMS: To assess changes in the prescribing practices and views about nurse
      prescribing of Registered Nurses in the Netherlands between 2006 and 2012.
      BACKGROUND: Considering the developments that took place in the Netherlands
      between 2006 and 2012, such as increased opportunities for nurse prescribing
      education and stricter control of nurses' prescribing practices, this study
      examines the extent to which nurses' prescribing practices and views have changed
      in the intervening years. In both years, nurses were not legally allowed to
      prescribe. DESIGN: Survey study. METHODS: Surveys were conducted in 2006 and
      2012. Questionnaires were sent to a national sample of nurses. The questionnaires
      addressed nurses' views on nurse prescribing and the extent to which nurse
      prescribing took place in the respondents' work setting. RESULTS: There were 386
      and 644 respondents to the 2006 and 2012 surveys respectively. The proportion of
      nurses who said that they felt adequately equipped to prescribe medicines
      remained constant around 12%. Insufficient knowledge to prescribe remained the
      most important reason for feelings of inadequacy. More than a quarter of the
      nurses in both surveys stated that nurses in their team sometimes write
      prescriptions. There were few changes in views on the consequences of nurse
      prescribing for nurses' practice. CONCLUSION: Overall, nurses' support for nurse
      prescribing remained stable at a fairly cautious level, while the number of
      nurses feeling inadequately equipped to prescribe remained high. As nurse
      prescribing is expected to improve the quality and continuity of care, this
      should be taken into account in policy expectations.

PMID- 24673627
TI  - Whole transcriptome sequencing of a paediatric case of de novo acute myeloid
      leukaemia with del(5q) reveals RUNX1-USP42 and PRDM16-SKI fusion transcripts.

PMID- 24673628
TI  - Novel peptide-based platform for the dual presentation of biologically active
      peptide motifs on biomaterials.
AB  - Biofunctionalization of metallic materials with cell adhesive molecules derived
      from the extracellular matrix is a feasible approach to improve cell-material
      interactions and enhance the biointegration of implant materials (e.g.,
      osseointegration of bone implants). However, classical biomimetic strategies may
      prove insufficient to elicit complex and multiple biological signals required in
      the processes of tissue regeneration. Thus, newer strategies are focusing on
      installing multifunctionality on biomaterials. In this work, we introduce a novel
      peptide-based divalent platform with the capacity to simultaneously present
      distinct bioactive peptide motifs in a chemically controlled fashion. As a proof
      of concept, the integrin-binding sequences RGD and PHSRN were selected and
      introduced in the platform. The biofunctionalization of titanium with this
      platform showed a positive trend towards increased numbers of cell attachment,
      and statistically higher values of spreading and proliferation of osteoblast-like
      cells compared to control noncoated samples. Moreover, it displayed statistically
      comparable or improved cell responses compared to samples coated with the single
      peptides or with an equimolar mixture of the two motifs. Osteoblast-like cells
      produced higher levels of alkaline phosphatase on surfaces functionalized with
      the platform than on control titanium; however, these values were not
      statistically significant. This study demonstrates that these peptidic structures
      are versatile tools to convey multiple biofunctionality to biomaterials in a
      chemically defined manner. 

PMID- 24673629
TI  - Classes of oppositional-defiant behavior: concurrent and predictive validity.
AB  - BACKGROUND: Oppositional defiant disorder (ODD) has components of both
      irritability and defiance. It remains unclear whether children with variation in
      these domains have different adult outcomes. This study examined the concurrent
      and predictive validity of classes of oppositional defiant behavior. METHODS:
      Latent class analysis was performed on the oppositional defiant problems scale of
      the Child Behavior Checklist in two samples, one in the US (the Achenbach
      Normative Sample, N = 2029) and one in the Netherlands (the Zuid-Holland Study, N
      = 2076). A third sample of American children (The Vermont Family Study, N = 399)
      was examined to determine concurrent validity with DSM diagnoses. Predictive
      validity over 14 years was assessed using the Zuid-Holland Study. RESULTS: Four
      classes of oppositional defiant problems were consistent in the two latent class
      analyses: No Symptoms, All Symptoms, Irritable, and Defiant. Individuals in the
      No Symptoms Class were rarely diagnosed concurrently with ODD or any future
      disorder. Individuals in the All Symptoms Class had an increased frequency of
      concurrent childhood diagnosis of ODD and of violence in adulthood. Subjects in
      the Irritable Class had low concurrent diagnosis of ODD, but increased odds of
      adult mood disorders. Individuals in the Defiant Class had low concurrent
      diagnosis of ODD, but had increased odds of violence as adults. CONCLUSIONS: Only
      children in the All Symptoms class were likely to have a concurrent diagnosis of
      ODD. Although not diagnosed with ODD, children in the Irritable Class were more
      likely to have adult mood disorders and children in the Defiant Class were more
      likely to engage in violent behavior.

PMID- 24673631
TI  - Dynamics of excited sodium atoms attached to helium nanodroplets.
AB  - The dynamics of laser-excited sodium atoms at the surface of helium nanodroplets
      has been investigated as a function of quantum state. For all cases, excitation
      of the system leads to desorption of the sodium atom from the droplet surface.
      The mean kinetic energy of the desorbed atoms scales linearly with excitation
      frequency, indicative of an impulsive desorption process. The energy partitioning
      between the helium and the desorbing sodium atom depends on the quantum state and
      appears to be related to the size and shape of the electron orbital. The speed
      distributions of desorbed NaHe exciplexes point toward a direct formation process
      of an exciplex with no internal energy. Photoelectron spectroscopy reveals an
      increasing importance of helium-induced relaxation with increasing quantum state,
      which is tentatively attributed to curve crossing between different NaHeN
      interaction potentials during the desorption process. 

PMID- 24673630
TI  - The clinical efficacy of dietary fat restriction in treatment of dogs with
      intestinal lymphangiectasia.
AB  - BACKGROUND: Intestinal lymphangiectasia (IL), a type of protein-losing
      enteropathy (PLE), is a dilatation of lymphatic vessels within the
      gastrointestinal tract. Dietary fat restriction previously has been proposed as
      an effective treatment for dogs with PLE, but limited objective clinical data are
      available on the efficacy of this treatment. HYPOTHESIS/OBJECTIVES: To
      investigate the clinical efficacy of dietary fat restriction in dogs with IL that
      were unresponsive to prednisolone treatment or showed relapse of clinical signs
      and hypoalbuminemia when the prednisolone dosage was decreased. ANIMALS: Twenty
      four dogs with IL. METHODS: Retrospective study. Body weight, clinical activity
      score, and hematologic and biochemical variables were compared before and 1 and 2
      months after treatment. Furthermore, the data were compared between the group fed
      only an ultra low-fat (ULF) diet and the group fed ULF and a low-fat (LF) diet.
      RESULTS: Nineteen of 24 (79%) dogs responded satisfactorily to dietary fat
      restriction, and the prednisolone dosage could be decreased. Clinical activity
      score was significantly decreased after dietary treatment compared with before
      treatment. In addition, albumin (ALB), total protein (TP), and blood urea
      nitrogen (BUN) concentration were significantly increased after dietary fat
      restriction. At 2 months posttreatment, the ALB concentrations in the ULF group
      were significantly higher than that of the ULF + LF group. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Dietary fat restriction appears to be an effective treatment
      in dogs with IL that are unresponsive to prednisolone treatment or that have
      recurrent clinical signs and hypoalbuminemia when the dosage of prednisolone is
      decreased.

PMID- 24673632
TI  - Small molecule modulators of protein-protein interactions: selected case studies.

PMID- 24673634
TI  - The dopamine transporter expression level differentially affects responses to
      cocaine and amphetamine.
AB  - Although both cocaine and amphetamine mainly target the dopamine transporter
      (DAT) and cause psychomotor effects, they have very different mechanisms of
      actions. The authors examined whether responses to cocaine and amphetamine were
      affected differentially by changes in DAT expression levels using transgenic mice
      with different DAT expression levels. In the constitutive DAT knockdown mice,
      reduced DAT expression enhanced cocaine's locomotor stimulatory effects and at
      the same time diminished amphetamine's locomotor stimulatory effects. Similar
      effects were observed in the inducible DAT knockdown mice, ruling out the
      contribution of developmental compensations in DAT knockdown mice. Extracellular
      dopamine levels in response to psychostimulants were assessed by in vivo
      microdialysis. Whereas amphetamine-induced increase in extracellular dopamine was
      drastically diminished in constitutive DAT knockdown mice, cocaine-induced
      increase in extracellular dopamine had a faster onset in knockdown mice compared
      with wild-type controls. Postsynaptically, D1 agonist-stimulated c-fos expression
      was significantly attenuated in constitutive DAT knockdown mice compared with
      wild-type controls. The authors propose that responses to cocaine and amphetamine
      depend on psychostimulant drug type, drug dose, as well as DAT expression level.
      DAT expression level affects presynaptic responses to psychostimulants directly
      and postsynaptic responses to psychostimulants indirectly via changes in receptor
      signaling. These data imply that individual differences in DAT expression (either
      genetically or pharmacologically induced) may affect susceptibility to addiction
      of different types of psychostimulants.

PMID- 24673635
TI  - Dietary fiber and fiber fraction intakes and colorectal cancer risk in Chinese
      adults.
AB  - Few studies have been conducted in Chinese adults to investigate the effect of
      fiber intake on colorectal cancer risk. The present study aimed to examine the
      associations of dietary fiber and fiber fraction intakes with colorectal cancer
      risk in Chinese adults. A total of 613 cases with colorectal cancer were
      consecutively recruited between July 2010 and October 2012 and frequency matched
      to 613 controls by age (5-yr interval) and gender. Dietary information was
      collected through a validated food frequency questionnaire by face-to-face
      interviews. Multivariate logistic regression models were used to estimate the
      odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for
      potential confounders. Total dietary fiber and fiber fraction intakes were found
      to be inversely associated with colorectal cancer risk. Compared with the lowest
      quartile, the adjusted ORs (95% CIs) for the highest quartile were 0.38 (0.27
      0.55) for total dietary fiber, 0.45 (0.32-0.64) for vegetable fiber, and 0.41
      (0.28-0.58) for fruit fiber, respectively. In addition, no significant
      association was found between soy fiber intake and colorectal cancer risk. This
      study showed that a high intake of dietary fiber, particularly derived from
      vegetables and fruit, was inversely associated with colorectal cancer risk in
      Chinese adults. 

PMID- 24673633
TI  - Superoxide dismutase 3 dysregulation in a murine model of neonatal lung injury.
AB  - Bronchopulmonary dysplasia (BPD), a common chronic respiratory disease that
      occurs after premature birth, is believed to be secondary to oxidative damage
      from hyperoxia and inflammation, which leads to impaired alveolar formation and
      chronic lung dysfunction. We hypothesized that extracellular superoxide dismutase
      (SOD)3, an antioxidant uniquely targeted to the extracellular matrix (ECM) and
      alveolar fluid, might have a different response (down-regulation) to hyperoxic
      injury and recovery in room air (RA), thereby contributing to the persistent
      airspace injury and inflammation. We used a murine BPD model using postnatal
      hyperoxia (O2) (4 or 5 d) followed by short-term recovery (14 d) in RA, which
      mimics the durable effects after injury during alveolar development. This was
      associated with significantly increased mRNA expression for antioxidant genes
      mediated by nuclear factor erythroid 2-related factor (Nrf2) in the O2 (n = 4)
      versus RA group (n = 5). SOD3, an Nrf2-independent antioxidant, was significantly
      reduced in the O2-exposed mice compared with RA. Immunohistochemistry revealed
      decreased and disrupted SOD3 deposition in the alveolar ECM of O2-exposed mice.
      Furthermore, this distinct hyperoxic antioxidant and injury profile was
      reproducible in murine lung epithelial 12 cells exposed to O2. Overexpression of
      SOD3 rescued the injury measures in the O2-exposed cells. We establish that
      reduced SOD3 expression correlates with alveolar injury measures in the recovered
      neonatal hyperoxic lung, and SOD3 overexpression attenuates hyperoxic injury in
      an alveolar epithelial cell line. Such findings suggest a candidate mechanism for
      the pathogenesis of BPD that may lead to targeted interventions. 

PMID- 24673637
TI  - Combined effects of brain-derived neurotrophic factor immobilized poly-lactic-co
      glycolic acid membrane with human adipose-derived stem cells and basic fibroblast
      growth factor hydrogel on recovery of erectile dysfunction.
AB  - Erectile dysfunction (ED) is the most frequent long-term problem after radical
      prostatectomy. We aimed to evaluate whether the use of combination therapy with
      basic fibroblast growth factor (bFGF)-hydrogel on corpus cavernosum and with
      adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF)
      immobilized poly-lactic-co-glycolic acid (PLGA) membrane on the cavernous nerve
      (CN) could improve erectile function in a rat model of bilateral cavernous nerve
      crush injury (BCNI). Rats were randomly divided into five groups (n=15 per
      group): a normal group (N group), a group receiving saline application after
      bilateral cavernous nerve crush injury (BCNI), a group undergoing bFGF-hydrogel
      injection in the corpus cavernosum after BCNI (bFGF), a group receiving ADSC
      application covered with BDNF-membrane after BCNI (ADSC/BDNF), and a group
      undergoing coadministration of bFGF-hydrogel injection and BDNF-membrane with
      ADSCs after BDNF (bFGF+ADSC/BDNF). Four weeks postoperatively, the erectile
      function was assessed by detecting the ratio of intracavernous pressure (ICP) to
      mean arterial pressure (MAP). Smooth muscle and collagen contents were measured
      using Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS)
      expression in the dorsal penile nerve was detected by immunostaining. The protein
      expression of the alpha-smooth muscle actin (alpha-SMA) and the cyclic guanosine
      monophosphate (cGMP) level of the corpus cavernosum were quantified by western
      blot and cGMP assay, respectively. In the bFGF+ADSC/BDNF group, the erectile
      function was significantly elevated compared with the BCNI and other treated
      groups and showed a significantly increased smooth muscle/collagen ratio, nNOS
      content, alpha-SMA expression, and cGMP level. In particular, there were no
      statistical differences in the ICP/MAP ratio, smooth muscle/collagen ratio, and
      alpha-SMA and cGMP levels between the bFGF+ADSC/BDNF group and normal group.
      Application of the BDNF-immobilized PLGA membrane with human ADSC into the CN and
      bFGF-incorporated hydrogel into the corpus carvernosum improved nearly normal
      erectile function in a rat model of postprostatectomy ED. This result suggests
      that a combined application of bFGF+ADSC/BDNF might be a promising treatment for
      postprostatectomy ED. 

PMID- 24673639
TI  - Myopia control: the time is now.

PMID- 24673638
TI  - A novel large deletion of the DOCK8 gene in a Chinese family with autosomal
      recessive hyper-IgE syndrome.
AB  - BACKGROUND: Autosomal-recessive hyper-IgE syndrome (AR-HIES; OMIM 243700) is a
      rare primary immunodeficiency disorder mainly caused by mutations in the
      dedicator of cytokinesis-8 (DOCK8) gene. DOCK8 is highly expressed in the immune
      system and plays important roles in regulation of lymphocyte functions.
      OBJECTIVE: We analysed the molecular basis of AR-HIES in a Chinese family.
      METHODS: A Chinese pedigree of typical AR-HIES was subjected to mutation
      detection in the DOCK8 gene. All exons of the DOCK8 gene and adjacent exon-intron
      border sequences were amplified using polymerase chain reaction and directly
      sequenced. RESULTS: We identified a novel large deletion of 1481 bp in the DOCK8
      gene, encompassing the totality of exon 11 (c.1126_1285del). CONCLUSION: Our data
      expand the spectrum of mutations in the DOCK8 gene underlying AR-HIES.

PMID- 24673640
TI  - Incidence of diabetes mellitus in a population-based cohort of HIV-infected and
      non-HIV-infected persons: the impact of clinical and therapeutic factors over
      time.
AB  - AIMS: To examine incidence density rate and correlates of incident diabetes
      mellitus in a cohort of HIV-infected individuals compared with matched non-HIV
      infected persons. METHODS: Data were obtained from the South Carolina Medicaid
      system and the enhanced HIV/AIDS Reporting System surveillance database for
      persons >= 18 years of age who had been attended to during the period 1994 to
      2011. Time-dependent proportional hazards analysis and marginal structural models
      were used to analyse the data. RESULTS: A total of 13 632 individuals (6816, 1:1
      matched HIV-infected and non-HIV-infected persons; median age 39 years; 57% male)
      contributed 88 359 person-years of follow-up. Incidence rate of diabetes was
      higher in the non-HIV-infected group compared with the HIV-infected group (13.60
      vs. 11.35 per 1000 person-years). Multivariable hazards analysis suggested a
      significantly lower risk of incident diabetes among HIV-infected persons treated
      with combination antiretroviral therapy compared with the matched non-HIV
      infected persons (adjusted hazards ratio 0.55; 95% CI 0.46-0.65). Among HIV
      infected persons, marginal structural modelling suggested a significantly higher
      risk of diabetes with cumulative exposure to protease inhibitors over the
      observation period (adjusted relative risk 1.35; 95% CI 1.03-1.78), but this
      association was not significant for exposure to non-nucleoside reverse
      transcriptase inhibitors. Overall, female gender, older age, non-white
      race/ethnicity, and pre-existing hypertension, dyslipidaemia, obesity and
      hepatitis C infection were associated with higher risk of diabetes incidence.
      CONCLUSIONS: HIV infection may not be independently associated with increased
      risk of diabetes. Among HIV-infected persons, exposure to protease inhibitor
      based regimens may increase the risk of diabetes. Healthcare providers should
      make every effort to use combination antiretroviral therapy regimens with a
      better cardiometabolic profile.

PMID- 24673641
TI  - The evaluation of inflammatory markers in umbilical cord blood.
AB  - We have read with great interest the article by Lausten-Thomsen et al. entitled
      "Inflammatory Markers in Umbilical Cord Blood from Small-For-Gestational-Age
      Newborns" in which they report Interleukin 6 (IL-6), Tumor necrosis factor-alpha
      (TNF-alpha) and C-reactive protein (CRP) levels in umbilical cord blood from
      small-for-gestational-age (SGA) and healthy newborns. In this regard, we would
      like to make some additions to paper in respect to interpretations of biochemical
      markers. Normal CRP concentration in healthy human serum is usually lower than 10
      mg/L, slightly increasing with aging. Acute inflammatory response causes release
      of IL-6 and other cytokines that trigger the synthesis of CRP by the liver. In
      this article, IL-6 levels reported as elevated but CRP levels have remained in
      normal range. In this situation, increasing in IL-6 levels should be approached
      suspiciously. Although decreased TNF-alpha level was compatible with IL-6 levels,
      increased IL-6 levels did not cause CRP elevation in this study.

PMID- 24673642
TI  - Busting robustness: using cancer's greatest strength to our advantage.
AB  - What do complex networks, such as those found in cancer cells, airplane flight
      patterns and the Internet have in common? A remarkable robustness with a
      surprising vulnerability. Complex networks follow remarkably similar patterns
      across seemingly unconnected fields, and it is possible that cancer researchers
      could thus learn from the advances in complex network theory. Very limited, yet
      coordinated, specific targeting of the most critical parts of a network can have
      dramatically outsized effects. "At times, our strengths propel us so far forward
      we can no longer endure our weaknesses and perish from them." Nietzsche.

PMID- 24673643
TI  - More insights into the immunocompromised district.

PMID- 24673645
TI  - Effects of radiofrequency procedure on hypertrophic scar due to burns.

PMID- 24673644
TI  - OmpA and OmpC are critical host factors for bacteriophage Sf6 entry in Shigella.
AB  - Despite being essential for successful infection, the molecular cues involved in
      host recognition and genome transfer of viruses are not completely understood.
      Bacterial outer membrane proteins A and C co-purify in lipid vesicles with
      bacteriophage Sf6, implicating both outer membrane proteins as potential host
      receptors. We determined that outer membrane proteins A and C mediate Sf6
      infection by dramatically increasing its rate and efficiency. We performed a
      combination of in vivo studies with three omp null mutants of Shigella flexneri,
      including classic phage plaque assays and time-lapse fluorescence microscopy to
      monitor genome ejection at the single virion level. Cryo-electron tomography of
      phage 'infecting' outer membrane vesicles shows the tail needle contacting and
      indenting the outer membrane. Lastly, in vitro ejection studies reveal that
      lipopolysaccharide and outer membrane proteins are both required for Sf6 genome
      release. We conclude that Sf6 phage entry utilizes either outer membrane proteins
      A or C, with outer membrane protein A being the preferred receptor. 

PMID- 24673646
TI  - Air breathing in Magadi tilapia Alcolapia grahami, under normoxic and hyperoxic
      conditions, and the association with sunlight and reactive oxygen species.
AB  - Observations of the Magadi tilapia Alcolapia grahami in hot, highly alkaline Lake
      Magadi revealed that they air breathe not only during hypoxia, as described
      previously, but also during normoxia and hyperoxia. Air breathing under these
      latter conditions occurred within distinct groupings of fish (pods) and involved
      only a small proportion of the population. Air breathing properties (duration and
      frequency) were quantified from video footage. Air breathing within the
      population followed a diel pattern with the maximum extent of pod formation
      occurring in early afternoon. High levels of reactive oxygen species (ROS) in the
      water may be an irritant that encourages the air-breathing behaviour. The diel
      pattern of air breathing in the field and in experiments followed the diel
      pattern of ROS concentrations in the water which are amongst the highest reported
      in the literature (maximum daytime values of 2.53 - 8.10 MUM H2O2). Interlamellar
      cell masses (ILCM) occurred between the gill lamellae of fish from the lagoon
      with highest ROS and highest oxygen levels, while fish from a normoxic lagoon
      with one third the ROS had little or no ILCM. This is the first record of air
      breathing in a facultative air-breathing fish in hyperoxic conditions and the
      first record of an ILCM in a cichlid species.

PMID- 24673647
TI  - Adipose invariant natural killer T cells.
AB  - Adipose tissue is a dynamic organ that makes up a substantial proportion of the
      body; in severe obesity it can account for 50% of body mass. Details of the
      unique immune system resident in human and murine adipose tissue are only
      recently emerging, and so it has remained a largely unexplored and unappreciated
      immune site until now. Adipose tissue harbours a unique collection of immune
      cells, which often display unusual functions compared with their counterparts
      elsewhere in the body. These resident immune cells are key to maintaining tissue
      and immune homeostasis, yet in obesity their chronic aberrant stimulation can
      contribute to the inflammation and pathogenesis associated with obesity. Anti
      inflammatory adipose-resident lymphocytes are often depleted in obesity, whereas
      pro-inflammatory immune cells accumulate, leading to an overall inflammatory
      state, which is a key step in the development of obesity-induced metabolic
      disease. A good example is invariant natural killer T (iNKT) cells, which make up
      a large proportion of lymphocytes in human and murine adipose tissue. Here, they
      are unusually poised to produce anti-inflammatory or regulatory cytokines,
      however in obesity, iNKT cells are greatly reduced. As iNKT cells are potent
      transactivaors of other immune cells, and can act as a bridge between innate and
      adaptive immunity, their loss in obesity represents the loss of a major
      regulatory population. Restoring iNKT cells, or activating them in obese mice
      leads to improved glucose handling, insulin sensitivity, and even weight loss,
      and hence represents an exciting therapeutic avenue to be explored for restoring
      homeostasis in obese adipose tissue. 

PMID- 24673648
TI  - Kinematics of signature writing in healthy aging.
AB  - Forensic document examiners (FDE) called upon to distinguish a genuine from a
      forged signature of an elderly person are often required to consider the question
      of age-related deterioration and whether the available exemplars reliably capture
      the natural effects of aging of the original writer. An understanding of the
      statistical relationship between advanced age and handwriting movements can
      reduce the uncertainty that may exist in an examiner's approach to questioned
      signatures formed by elderly writers. The primary purpose of this study was to
      systematically examine age-related changes in signature kinematics in healthy
      writers. Forty-two healthy subjects between the ages of 60-91 years participated
      in this study. Signatures were recorded using a digitizing tablet, and commercial
      software was used to examine the temporal and spatial stroke kinematics and pen
      pressure. Results indicated that vertical stroke duration and dysfluency
      increased with age, whereas vertical stroke amplitude and velocity decreased with
      age. Pen pressure decreased with age. We found that a linear model characterized
      the best-fit relationship between advanced age and handwriting movement
      parameters for signature formation. Male writers exhibited stronger age effects
      than female writers, especially for pen pressure and stroke dysfluency. The
      present study contributes to an understanding of how advanced age alters
      signature formation in otherwise healthy adults.

PMID- 24673649
TI  - Efficacy of ofatumumab against rituximab-resistant B-CLL/SLL cells with low CD20
      protein expression.

PMID- 24673650
TI  - Risk of seizure recurrence after achieving initial seizure freedom on the
      ketogenic diet.
AB  - OBJECTIVE: Few studies have examined the long-term sustainability of complete
      seizure freedom on the ketogenic diet (KD). The purpose of this study was to
      describe the risk of seizure recurrence in children who achieved at least 1 month
      of seizure freedom on the KD, and to assess clinical features associated with
      sustained seizure freedom. METHODS: Records of patients initiated on the KD at
      The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed.
      Subjects who attained seizure freedom for at least 1 month within 2 years were
      included in the study. Seizure frequency was recorded based on caregiver-reported
      seizure diaries as unchanged, improved, or worse compared to baseline. Those
      patients with seizure freedom >=1 year were compared to those with seizure
      freedom <1 year in terms of demographics, age of seizure onset, number of
      antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. RESULTS: Of
      276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for
      a minimum of 1 month. The majority of these patients had daily seizures. The
      median time to seizure freedom after KD initiation was 1.5 months. Seizures
      recurred in 53 patients (82%), with a median time to seizure recurrence of 3
      months. However, seizure frequency after initial recurrence remained far less
      than baseline. No clinical features were identified as risk factors for seizure
      recurrence. SIGNIFICANCE: Seizure recurrence on the KD after 1 month of seizure
      freedom most often occurred as occasional breakthrough seizures and not a return
      to baseline seizure frequency. This study provides evidence to support the
      continued use of the KD in patients with initial seizure freedom even after
      breakthrough seizures. A PowerPoint slide summarizing this article is available
      for download in the Supporting Information section here.

PMID- 24673651
TI  - Testing the temporal stability of individual differences in the acquisition and
      generalization of fear.
AB  - We studied the temporal stability of individual differences in the acquisition
      and generalization of fear. Seventy-one participants were tested in two almost
      identical fear-acquisition and fear-generalization sessions (separated by 8
      months). Acquisition and generalization were measured by the fear-potentiated
      startle, the skin conductance response, and online expectancies of the
      unconditioned stimulus. To control for the effects of previous experience,
      different stimuli were used for half of the participants in Session 2.
      Acquisition and generalization did not differ across sessions or as a function of
      the stimuli used in Session 2, and a significant proportion of individual
      differences in these processes was stable over time (generalizability
      coefficients ranged from 0.17 to 0.38). When the same stimuli were used,
      acquisition measures showed compromised stability. The results are discussed in
      terms of their theoretical and applied implications. 

PMID- 24673653
TI  - Small Molecules of Cyclopentadithiophene Derivatives: Effect of Sulfur Atoms
      Position and Substituted Groups on Their UV-abs Properties.
AB  - Thiophene-based organic semiconductors used as the active components have
      received much attention. Their photoelectric properties can be easily tuned with
      various substitutions at different positions on molecular structures. Here, we
      synthesized series cyclopentadithiophene (CDT) derivatives with sulfur atoms at
      ortho- (o-CDT), meta- (m-CDT) and para-position (p-CDT) of the bridge carbon.
      These CDT derivatives were substituted by carbonyl/dicyanomethylene at the bridge
      position and/or by phenyl groups at alpha position, respectively. Due to the
      different conjugation extent and the variation of donor-acceptor (D-A)
      interaction originating from the change of sulfur atom position, diverse
      absorption spectra were observed. Especially for dicyanomethylene substituted o
      CDT with phenyl as substitution group (DPCN-o-CDT), its absorption spectrum
      covers the whole region of visible light. Combining with the electrochemical
      behaviors and theoretical calculations, it was found that the sulfur atoms mainly
      contribute to the molecular conjugation in these CDT derivatives, especially for
      o-CDT derivatives. For phenyl groups, they primarily act as electron donor in m
      CDT derivatives, and chiefly contribute to molecular conjugation in p-CDT
      derivatives, and simultaneously work as electron donor and conjugation component
      in o-CDT derivatives, respectively.

PMID- 24673652
TI  - 2D NMR barcoding and differential analysis of complex mixtures for chemical
      identification: the Actaea triterpenes.
AB  - The interpretation of NMR spectroscopic information for structure elucidation
      involves decoding of complex resonance patterns that contain valuable molecular
      information (delta and J), which is not readily accessible otherwise. We
      introduce a new concept of 2D-NMR barcoding that uses clusters of fingerprint
      signals and their spatial relationships in the delta-delta coordinate space to
      facilitate the chemical identification of complex mixtures. Similar to widely
      used general barcoding technology, the structural information of individual
      compounds is encoded as a specifics pattern of their C,H correlation signals.
      Software-based recognition of these patterns enables the structural
      identification of the compounds and their discrimination in mixtures. Using the
      triterpenes from various Actaea (syn. Cimicifuga) species as a test case,
      heteronuclear multiple-bond correlation (HMBC) barcodes were generated on the
      basis of their structural subtypes from a statistical investigation of their
      deltaH and deltaC data in the literature. These reference barcodes allowed in
      silico identification of known triterpenes in enriched fractions obtained from an
      extract of A. racemosa (black cohosh). After dereplication, a differential
      analysis of heteronuclear single-quantum correlation (HSQC) spectra even allowed
      for the discovery of a new triterpene. The 2D barcoding concept has potential
      application in a natural product discovery project, allowing for the rapid
      dereplication of known compounds and as a tool in the search for structural
      novelty within compound classes with established barcodes. 

PMID- 24673654
TI  - A case series of real-time hemodynamic assessment of high output heart failure as
      a complication of arteriovenous access in dialysis patients.
AB  - Congestive heart failure (CHF) is an important source of morbidity and mortality
      in end-stage renal disease patients. Although CHF is commonly associated with low
      cardiac output (CO), it may also occur in high CO states. Multiple conditions are
      associated with increased CO including congenital or acquired arteriovenous
      fistulae or arteriovenous grafts. Increased CO resulting from permanent AV access
      in dialysis patients has been shown to induce structural and functional cardiac
      changes, including the development of eccentric left ventricle hypertrophy.
      Often, the diagnosis of high output heart failure requires invasive right heart
      monitoring in the acute care setting such as a medical or cardiac intensive care
      unit. The diagnosis of an arteriovenous access causing high output heart failure
      is usually confirmed after the access is ligated surgically. We present for the
      first time, a case for real-time hemodynamic assessment of high output heart
      failure due to AV access by interventional nephrology in the cardiac
      catheterization suite. 

PMID- 24673656
TI  - Embodied practice: rediscovering the 'heart' of nursing.
AB  - AIM: This article explores the importance of embodiment in nursing. It examines
      different sources of authoritative knowledge concerning the body and embodiment.
      It argues that dominant scientific and medical epistemologies of the body have
      displaced and marginalized embodied epistemologies, creating only a partial
      understanding of the embodied experiences of our patients and our own embodiment
      as nurses. BACKGROUND: Over the last 20 years, there has been a rapid expansion
      of theoretical literature concerning the body and embodiment, spanning a range of
      disciplines. The potential of these insights to the essentially 'body-based'
      practice of nursing is highly significant. However, although work in this area is
      now increasing, theoretical and empirical investigation of the body and
      embodiment in nursing has remained relatively neglected. DESIGN: Discussion
      paper. DATA SOURCES: Conventional approaches to systematic searching of the
      literature were not adopted for this conceptual paper. Seminal texts
      predominantly from nursing and sociology accompanied by more recent sources were
      used as a platform for theoretical reflection and to inform development of the
      conceptual arguments. IMPLICATIONS FOR NURSING: The paper proposes a corporeal
      (re)turn to nursing practice, one that recognizes the lived embodied experience
      of the patient and the embodied skill and knowledge of the nurse and examines the
      implications for contemporary person-centred nursing practice, research and
      education. CONCLUSION: At a significant juncture in nursing's history, when there
      is greater international focus on delivering higher standards of care, the paper
      calls for a repositioning of the place of embodiment in nursing.

PMID- 24673655
TI  - Understanding the adsorption interface of polyelectrolyte coating on redox active
      nanoparticles using soft particle electrokinetics and its biological activity.
AB  - The application of cerium oxide nanoparticles (CNPs) for therapeutic purposes
      requires a stable dispersion of nanoparticles in a biological environment. The
      objective of this study is to tailor the properties of polyelectrolyte coated
      CNPs as a function of molecular weight to achieve a stable and catalytic active
      dispersion. The coating of CNPs with polyacrylic acid (PAA) has increased the
      dispersion stability of CNPs and enhanced the catalytic ability. The stability of
      PAA coating was analyzed using the change in the Gibbs free energy computed by
      the Langmuir adsorption model. The adsorption isotherms were determined using
      soft particle electrokinetics which overcomes the challenges presented by other
      techniques. The change in Gibbs free energy was highest for CNPs coated with PAA
      of 250 kg/mol indicating the most stable coating. The change in free energy for
      PAA of 100 kg/mol coated CNPs was 85% lower than the PAA of 250 kg/mol coated
      CNPs. This significant difference is caused by the strong adsorption of PAA of
      100 kg/mol on CNPs. Catalytic activity of PAA-CNPs is assessed by the catalase
      enzymatic mimetic activity of nanoparticles. The catalase activity was higher for
      PAA coated CNPs as compared to bare CNPs which indicated preferential adsorption
      of hydrogen peroxide induced by coating. This indicates that the catalase
      activity is also affected by the structure of the coating layer. 

PMID- 24673657
TI  - The perception of facial asymmetry using 3-dimensional simulated images.
AB  - OBJECTIVE: To investigate the perception of facial asymmetry in young adults to
      identify the amounts of chin asymmetry that can be regarded as normal and may
      benefit from correction. MATERIALS AND METHODS: Three-dimensional (3D) images of
      56 individuals of mixed ethnicity were obtained and used to produce average 3D
      images of male and female faces. Distortion was then applied to these average
      faces using a 3D graphics package to simulate different amounts of chin point
      asymmetry. Five observer groups (lay individuals, dental students, dental care
      professionals, dental practitioners, and orthodontists) assessed timed
      presentations of 3D images, rating them as "normal," "acceptable," or "would
      benefit from correction." Time-to-event analysis was used to assess the level of
      chin asymmetry perceived as normal and beneficial for correction for each group.
      RESULTS: The factors influencing the perception of facial asymmetry were the
      degree of asymmetry and the observer group. Direction of the asymmetry and gender
      of the assessed individual did not affect the perception of asymmetry, except in
      the 4- to 6-mm distortion range. The gender of the observer had no influence on
      perception. There were statistically significant differences in the amounts of
      asymmetry that the laypeople and orthodontists considered to be normal (5.6 +/-
      2.7 mm and 3.6 +/- 1.5 mm, respectively; P < .001) and felt would benefit from
      surgical correction (11.8 +/- 4.0 mm and 9.7 +/- 3.0 mm, respectively; P  = 
      .001). CONCLUSIONS: Perception of asymmetry is affected by the amount of
      asymmetry and the observer group, with orthodontists being more critical.

PMID- 24673658
TI  - Dentofacial characteristics in orthodontic patients with centric relation-maximum
      intercuspation discrepancy.
AB  - INTRODUCTION: To investigate dentofacial characteristics of orthodontic patients
      with centric relation (CR)-maximum intercuspation (MI) discrepancy and to analyze
      changes in dentofacial characteristics between CR and MI positions in these
      patients using lateral cephalograms. MATERIALS AND METHODS: Adult female patients
      were classified into two groups: large CR-MI discrepancy (greater than 2.0 mm
      horizontal or vertical mandibular incisor movements during CR to MI change, n  = 
      20) and small CR-MI discrepancy (less than 1.0 mm horizontal and vertical
      mandibular incisor movements during CR to MI change, n  =  22). All subjects
      underwent temporomandibular joint (TMJ) magnetic resonance imaging prior to
      treatment. Gnathological stabilizing splints were used to find a reliable CR
      position in patients with large CR-MI discrepancy. Sixteen variables from lateral
      cephalograms were analyzed to identify differences in cephalometric variables
      between CR and MI positions in patients with large discrepancy. Differences in
      dentofacial cephalometric variables at MI positions between patients with large
      and small CR-MI discrepancies were also analyzed. RESULTS: Patients with large CR
      MI discrepancy had backward positioning and rotation of the mandible at the MI
      position compared to the norm. In addition, the mandible moved more posteriorly
      and rotated more in a clockwise direction during MI to CR change. Interestingly,
      all patients with large CR-MI discrepancy had TMJ disk displacement. There were
      no significant differences in the cephalometric variables of the MI positions
      between patients with small and large CR-MI discrepancies. CONCLUSIONS: This
      study suggests that adult patients with backward positioning and rotation of the
      mandible should be carefully evaluated as a result of the potential CR-MI
      discrepancy.

PMID- 24673659
TI  - Prediction of antiarthritic drug efficacies by monitoring active matrix
      metalloproteinase-3 (MMP-3) levels in collagen-induced arthritic mice using the
      MMP-3 probe.
AB  - Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid
      arthritis (RA). We recently developed an MMP-3 probe that can specifically detect
      the active form of MMP-3. The aim of this study was to investigate whether
      detection and monitoring of active MMP-3 could be useful to predict therapeutic
      drug responses in a collagen-induced arthritis (CIA) model. During the period of
      treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA
      and protein levels were correlated with fluorescence signals in arthritic joint
      tissues and in the serum of CIA mice. Also, bone volume density and erosion in
      the knee joints and the paws of CIA mice were measured with microcomputed
      tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint
      tissues and serum of CIA mice, strong fluorescence signals induced by the action
      of active MMP-3 were significantly decreased when drugs were applied. The
      decrease in RA scores in drug-treated CIA mice led to fluorescence reductions,
      mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X
      ray, and histology results clearly showed marked decreases in bone and cartilage
      destruction, which were consistent with the reduction of fluorescence by down
      regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3
      diagnostic kit could be used to detect and monitor the active form of MMP-3 in
      CIA mice serum during a treatment course and thereby used to predict the drug
      response or resistance to RA therapies at an earlier stage. We hope that
      monitoring of active MMP-3 levels in arthritis patients using the MMP-3
      diagnostic kit will be a promising tool for drug discovery, drug development, and
      monitoring of drug responses in RA therapy. 

PMID- 24673660
TI  - Listening effort and fatigue: what exactly are we measuring? A British Society of
      Audiology Cognition in Hearing Special Interest Group 'white paper'.
AB  - OBJECTIVE: There is growing interest in the concepts of listening effort and
      fatigue associated with hearing loss. However, the theoretical underpinnings and
      clinical meaning of these concepts are unclear. This lack of clarity reflects
      both the relative immaturity of the field and the fact that research studies
      investigating listening effort and fatigue have used a variety of methodologies
      including self-report, behavioural, and physiological measures. DESIGN: This
      discussion paper provides working definitions for listening effort and listening
      related fatigue. Using these definitions as a framework, methodologies to assess
      these constructs are reviewed. RESULTS: Although each technique attempts to
      characterize the same construct (i.e. the clinical presentation of listening
      effort and fatigue), different assumptions are often made about the nature of
      these phenomena and their behavioural and physiological manifestations.
      CONCLUSION: We suggest that researchers consider these assumptions when
      interpreting their data and, where possible, make predictions based on current
      theoretical knowledge to add to our understanding of the underlying mechanisms of
      listening effort and listening-related fatigue. FOREWORD: Following recent
      interest in the cognitive involvement in hearing, the British Society of
      Audiology (BSA) established a Special Interest Group on Cognition in Hearing in
      May 2013. In an exploratory group meeting, the ambiguity surrounding listening
      effort and fatigue was discussed. To address this problem, the group decided to
      develop a 'white paper' on listening effort and fatigue. This is a discussion
      document followed by an international set of commentaries from leading
      researchers in the field. An approach was made to the editor of the International
      Journal of Audiology who agreed to this suggestion. This paper, and the
      associated commentaries that follow, are the result.

PMID- 24673661
TI  - The effect of notch filtering on the waveform of the newborn auditory brainstem
      response.
AB  - OBJECTIVE: To identify whether the use of a notch filter significantly affects
      the morphology or characteristics of the newborn auditory brainstem response
      (ABR) waveform and so inform future guidance for clinical practice. DESIGN:
      Waveforms with and without the application of a notch filter were recorded from
      babies undergoing routine ABR tests at 4000, 1000 and 500 Hz. Any change in
      response morphology was judged subjectively. Response latency, amplitude, and
      measurements of response quality and residual noise were noted. An ABR simulator
      was also used to assess the effect of notch filtering in conditions of low and
      high mains interference. RESULTS: The use of a notch filter changed waveform
      morphology for 500 Hz stimuli only in 15% of tests in newborns. Residual noise
      was lower when 4000 Hz stimuli were used. Response latency, amplitude, and
      quality were unaffected regardless of stimulus frequency. Tests with the ABR
      stimulator suggest that these findings can be extended to conditions of high
      level mains interference. CONCLUSIONS: A notch filter should be avoided when
      testing at 500 Hz, but at higher frequencies appears to carry no penalty.

PMID- 24673662
TI  - Understanding and becoming - the heart of the matter in nurse education.
AB  - The aim of this study was to deepen the understanding of student nurses'
      processes of understanding and becoming nurses. The study is phenomenological
      hermeneutic in design, comprising data from three focus group interviews in two
      Scandinavian countries. The process of student nurses' understanding and becoming
      a nurse emerged as a hermeneutical movement. A caring student-preceptor
      relationship and a growth-promoting preception in a supportive and inclusive
      environment provide the frame within which the movement happens. The movement
      towards understanding and becoming is initiated as students, based on their level
      of knowledge, are given responsibility. In order to fulfil the responsibility
      imposed on them, students take their entire repertoire of knowledge into
      consideration. By tying these threads together, they found the basis for
      conscious action, and care is provided according to what the current situation
      requires. The experiences obtained are reflected on and integrated with earlier
      knowledge, which leads to enhanced understanding. Students form a new base to
      stand on. They show increased readiness for still more responsibility and action.
      This movement towards deeper understanding and becoming affects the students also
      ethically and deepens their ethical awareness. When one loop of understanding and
      becoming is closed the process continues by passing into a new loop. This
      movement could be described as a hermeneutical spiral consisting of
      interconnected loops taking the students further and deeper in their process of
      understanding and becoming a nurse. The student-preceptor relationship and the
      ethos permeating it are decisive for students' learning both epistemologically
      and ontologically. Responsibility is the catalyst in students' understanding and
      becoming both intellectually and ethically. Understanding and becoming are
      ongoing processes of appropriation, thus altering students both professionally
      and personally. Understanding and becoming can be perceived as the hearth of the
      matter in nurse education. 

PMID- 24673663
TI  - Observational study on the mitotic rate and other prognostic factors in cutaneous
      primary melanoma arising from naevi and from melanoma de novo.
AB  - BACKGROUND: Melanomas can arise from naevi or appear de novo. The frequency or
      the effect of their origin on prognosis is still debated. Mitotic rate (MR) and
      ulceration of melanomas have been proposed as further new prognostic indexes.
      AIM: To determine the different prognostic factors in melanomas de novo and
      melanomas from pre-existing naevi and whether these two melanoma groups have
      different MR or presence of ulceration. METHODS: All patients with confirmed
      primary melanomas observed in our clinic from 1996 to July 2013 were included.
      The distinction between the two groups of melanomas was histologically based. We
      compared Breslow's thickness, the number of mitosis/mm(2) and the presence of
      ulceration between the naevus-associated melanoma and de novo melanoma group.
      RESULTS: Of the 873 melanomas, 626 (71.8%) have a de novo melanoma, 247 (28.2%) a
      naevus-associated melanoma. Breslow's thickness was not significantly different
      in the two groups (0.77 +/- 1.47 mm vs. 0.59 +/- 1.35 mm). The number of patients
      with presence of ulceration and MR >=1 mitosis/mm(2) was not significantly
      different in the two groups (19.6% vs. 16.3%). In thicker melanomas (Breslow's
      thickness >= 1 mm), the number of patients with >=6 mitosis/mm(2) was
      significantly higher (26.6% vs. 7.9%; P < 0.05) in the de novo melanoma group.
      CONCLUSIONS: When mitosis >= 1 mm/mm(2) , the results obtained do not show a
      better or worse prognosis based on Breslow's thickness, ulceration and MR in
      melanomas associated with naevus vs. melanomas de novo. When >=6 mitosis/mm(2)
      are considered, the number of patients in the de novo melanoma group with thick
      melanoma is highly more represented. The debate about the cut-off value of
      mitosis >=1 mm(2) is open.

PMID- 24673664
TI  - Epidemiology of mass casualty incidents in the United States.
AB  - OBJECTIVE: We sought to characterize and estimate the frequency of mass casualty
      incidents (MCIs) occurring in the United States during the year 2010, as reported
      by emergency medical services (EMS) personnel. METHODS: Using the 2010 National
      EMS Database of the National Emergency Medical Services Information System
      (NEMSIS), containing data from 32 states and territories, we estimated and
      weighted the frequency of MCIs documented by EMS personnel based on their
      perception of the event to produce incidence rates of MCIs per 100,000 population
      and MCIs per 1,000 9-1-1 calls requesting EMS service. We conducted descriptive
      analyses to characterize the MCIs by geographic location, incident type, and time
      of day as well as the MCI patients by demographic and health information. We used
      chi-squared tests to compare response delays and two-tailed t-tests to compare
      system response times between EMS responses documented as MCIs and those not.
      RESULTS: Among the 9,776,094 EMS responses in the 2010 National EMS Database,
      14,504 entries were documented as MCI. These entries represented an estimated
      9,913 unique MCIs from the National EMS Database: 39.1% occurred in the South
      Atlantic region of the United States where only 19.1% of the population resides,
      60.9% occurred in an urban setting, and 58.4% occurred on a street or highway.
      There were an estimated 13,677 MCI patients. The prehospital EMS personnel's
      primary impressions of the patients ranged from electrocution (0.01%) to
      traumatic injury (40.7%). Of the patients with a primary impression of injury (N
      = 7,960), motor vehicle traffic crash was the cause of injury for 62.7%. Among
      the MCI EMS responses, 47.6% documented experiencing a response delay compared to
      only 12.3% of non-MCI EMS responses. CONCLUSIONS: This study demonstrates the
      range of health conditions and characteristics of EMS responses that EMS
      personnel perceive as MCIs, suggests that response delays are common during MCIs,
      and indicates there may be underreporting of all persons involved in an MCI. The
      National EMS Database is useful for describing MCIs and may help guide national
      leadership in strengthening EMS system preparedness for MCIs.

PMID- 24673665
TI  - The CcpA regulon of Streptococcus suis reveals novel insights into the regulation
      of the streptococcal central carbon metabolism by binding of CcpA to two distinct
      binding motifs.
AB  - Streptococcus suis (S. suis) is a neglected zoonotic streptococcus causing fatal
      diseases in humans and in pigs. The transcriptional regulator CcpA (catabolite
      control protein A) is involved in the metabolic adaptation to different
      carbohydrate sources and virulence of S. suis and other pathogenic streptococci.
      In this study, we determined the DNA binding characteristics of CcpA and
      identified the CcpA regulon during growth of S. suis. Electrophoretic mobility
      shift analyses showed promiscuous DNA binding of CcpA to cognate cre sites in
      vitro. In contrast, sequencing of immunoprecipitated chromatin revealed two
      specific consensus motifs, a pseudo-palindromic cre motif (WWGAAARCGYTTTCWW) and
      a novel cre2 motif (TTTTYHWDHHWWTTTY), within the regulatory elements of the
      genes directly controlled by CcpA. Via these elements CcpA regulates expression
      of genes involved in carbohydrate uptake and conversion, and in addition in
      important metabolic pathways of the central carbon metabolism, like glycolysis,
      mixed-acid fermentation, and the fragmentary TCA cycle. Furthermore, our analyses
      provide evidence that CcpA regulates the genes of the central carbon metabolism
      by binding either the pseudo-palindromic cre motif or the cre2 motif in a
      HPr(Ser)~P independent conformation. 

PMID- 24673666
TI  - Adult scaphoid fracture.
AB  - OBJECTIVES: Scaphoid fractures are the most common carpal fracture, representing
      70% of carpal bone fractures. The diagnostic accuracy of physical examination
      findings and emergency medicine (EM) imaging studies for scaphoid fracture has
      not been previously described in the EM literature. Plain x-rays are insufficient
      to rule out scaphoid fractures in a patient with a suggestive mechanism and
      radial-sided tenderness on physical examination. This study was a meta-analysis
      of historical features, physical examination findings, and imaging studies for
      scaphoid fractures not visualized on plain x-ray in adult emergency department
      (ED) patients, specifically to address which types of imaging tests should be
      recommended in patients with persistent concern for acute fracture after ED
      discharge. METHODS: A medical librarian and two emergency physicians (EPs)
      conducted a medical literature search of PUBMED and EMBASE. The original studies'
      bibliographies were reviewed for additional references and unpublished
      manuscripts were located via a hand search of EM research abstracts from national
      meetings. All abstracts were independently reviewed by the two physicians, and
      Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) was used to
      assess individual study quality. When two or more qualitatively similar studies
      were identified, meta-analysis was conducted using Meta-DiSc software. Primary
      outcomes were sensitivity, specificity, and likelihood ratios (LRs) for
      predictors of scaphoid fracture detected on follow-up in patients with normal ED
      x-rays. RESULTS: A total of 957 unique citations were identified, yielding 75
      studies eligible for inclusion in this systematic review. Studies were
      significantly heterogeneous in design, study population, and criterion standard.
      The majority of studies were conducted in non-ED settings (e.g., orthopedic
      clinics). No studies used accepted diagnostic research publishing guidelines, and
      the overall QUADAS-2 methodologic quality was low, indicating an increased risk
      of bias in the estimates of diagnostic accuracy. The prevalence of scaphoid
      fractures ranged from 12% to 57% with the point estimate of 25% pretest
      probability for adult ED patients with concern for scaphoid injuries,
      nondiagnostic index x-rays, and scaphoid fractures on later imaging studies.
      Except for the absence of snuffbox tenderness (LR- = 0.15), physical examination
      findings lack accuracy to rule in or rule out scaphoid fractures, and no
      validated clinical decision rules exist. In patients with persistent concern for
      injury, magnetic resonance imaging (MRI) is superior to bone scan, computed
      tomography (CT), or ultrasound (US) to both rule in and rule out scaphoid
      fractures. Both MRI and CT share the added benefit of identifying alternative
      etiologies for posttraumatic wrist pain. CONCLUSIONS: Except for the absence of
      snuffbox tenderness, which can significantly reduce the probability of scaphoid
      fracture, history and physical examination alone are inadequate to rule in or
      rule out scaphoid fracture. MRI is the most accurate imaging test to diagnose
      scaphoid fractures in ED patients with no evidence of fracture on initial x-rays.
      If MRI is unavailable, CT is adequate to rule in scaphoid fractures, but
      inadequate for ruling out scaphoid fractures.

PMID- 24673667
TI  - Barriers to computed tomography radiation risk communication in the emergency
      department: a qualitative analysis of patient and physician perspectives.
AB  - OBJECTIVES: This qualitative study aimed to characterize the barriers to informed
      discussions between patients and emergency physicians (EPs) about radiation risk
      from computed tomography (CT) and to identify future interventions to improve
      patient understanding of CT radiation risk. METHODS: This study used a focus
      group approach to collect concepts about radiation risk exposure from a national
      sample of EPs and a local sample of emergency department (ED) patients. A
      directed content analysis used an a priori medical ethics framework to explore
      themes from the focus groups while a subsequent normative ethics analysis
      compared these results with existing perceptions about discussing CT radiation
      risk. RESULTS: Focus groups (three each for a total of 19 EPs and 27 patients)
      identified concepts consistent with core medical ethics principles: patients
      emphasized autonomy and nonmaleficence more than physicians, while physicians
      emphasized beneficence. Subjects' knowledge of radiation dose and risk were
      equivalent to previously published reports. When asked about whether they should
      talk about radiation with patients, 74% of EPs reported that radiation exposure
      should be discussed, but the study EPs self-reported doing so with only an
      average of 24% of patients. Patients reported wanting to hear about radiation
      from their physicians the next time they need CT scans and thought that a written
      handout would work better than any other method. When presented with options for
      how to discuss risk with patients, EPs reported needing easy access to risk
      information and preferred discussion over other communications approaches, but
      had mixed support of distributing patient handouts. CONCLUSIONS: The normative
      view that radiation from diagnostic CT should be discussed in the ED is shared by
      patients and physicians, but is challenged by the lack of a structured method to
      communicate CT radiation risk to ED patients. Our analysis identifies promising
      interest among physicians and patients to use information guides and electronic
      order prompts as potential informational tools to overcome this barrier.

PMID- 24673668
TI  - Ultrasound for routine lumbar puncture.
AB  - OBJECTIVES: The objective was to determine if use of ultrasound (US) by emergency
      physicians (EPs) to localize spinal landmarks improves the performance of lumbar
      puncture (LP). METHODS: This was a prospective, randomized, controlled study
      conducted in a county teaching hospital. Subjects, adults 18 years of age or
      older who were to receive LPs for routine clinical care in the emergency
      department (ED), were randomized either to undergo US localization of the
      puncture site or to have the puncture site determined by palpation of spinal
      landmarks. Primary outcomes were the number of needle insertion attempts and
      success of the procedure. Secondary outcomes were pain associated with the
      procedure, time to perform the procedure, number of traumatic taps, and patient
      satisfaction with the procedure. RESULTS: One-hundred patients were enrolled in
      the study, with 50 in each study group. There were no significant differences
      between the two groups in terms of age, sex, body mass index (BMI), indication
      for LP, or ease of palpation of landmarks. For both primary outcomes and
      secondary outcomes there were no significant differences between those undergoing
      US localization and those with palpation alone. CONCLUSIONS: These data do not
      suggest any advantage to the routine use of US localization for LP insertion,
      although further study may be warranted to look for benefit in the difficult to
      palpate or obese patient subgroups.

PMID- 24673670
TI  - Does numeracy correlate with measures of health literacy in the emergency
      department?
AB  - OBJECTIVES: The objective was to quantify the correlation between general
      numeracy and health literacy in an emergency department (ED) setting. METHODS:
      This was a prospective cross-sectional convenience sample study of adult patients
      in an urban, academic ED with 97,000 annual visits. General numeracy was
      evaluated using four validated questions and health literacy using three commonly
      used validated screening tools (Short Test of Functional Health Literacy in
      Adults [S-TOFHLA], Rapid Estimate of Adult Literacy in Medicine-Revised [REALM
      R], and the Newest Vital Sign [NVS]). Scores were dichotomized for health
      literacy tests to limited (low or marginal) versus adequate health literacy, and
      the proportion of patients answering all numeracy questions correctly was
      calculated with the mean proportion of correct responses in these groups. The
      correlation between numeracy scores and scores on the health literacy screening
      tools was evaluated using Spearman's correlation. RESULTS: A total of 446
      patients were enrolled. Performance on questions evaluating general numeracy was
      universally poor. Only 18 patients (4%) answered all numeracy questions
      correctly, 88 patients (20%) answered zero questions correctly, and overall the
      median number of correct answers was one (interquartile range [IQR] = 1 to 2).
      Among patients with limited health literacy (LHL) by any of the three screening
      tools used, the mean number of correct numeracy answers was approximately half
      that of patients with adequate health literacy. However, even among those with
      adequate health literacy, the average number of correct answers to numeracy
      questions ranged from 1.6 to 2.4 depending on the screening test used. When
      dichotomized into those who answered <=50% versus >50% of numeracy questions
      correctly, there was a significant difference between those with LHL and those
      who scored <=50% on numeracy. Health literacy screening results were correlated
      with general numeracy in the low to moderate range: S-TOFHLA rs  = 0.428 (p <
      0.0001); REALM, rs  = 0.400 (p < 0.0001); and NVS, rs  = 0.498 (p < 0.0001).
      CONCLUSIONS: Correlations between measures of general numeracy and measures of
      health literacy are in the low to moderate range. Performance on numeracy testing
      was nearly universally poor, even among patients performing well on health
      literacy screens, with a substantial proportion of the latter patients unable to
      answer half of the numeracy items correctly. Insofar as numeracy is considered a
      subset of health literacy, these results suggest that commonly used health
      literacy screening tools in ED-based studies inadequately evaluate and
      overestimate numeracy. This suggests the potential need for separate numeracy
      screening when these skills are important for health outcomes of interest.
      Providers should be sensitive to potential numeracy deficits among those who may
      otherwise have normal health literacy.

PMID- 24673669
TI  - Feasibility and diagnostic accuracy of brief health literacy and numeracy
      screening instruments in an urban emergency department.
AB  - OBJECTIVES: The objective was to evaluate the diagnostic accuracy of five health
      literacy screening instruments in emergency department (ED) patients: the Rapid
      Evaluation of Adult Literacy in Medicine-Revised (REALM-R), the Newest Vital Sign
      (NVS), Single Item Literacy Screens (SILS), health numeracy, and physician
      gestalt. A secondary objective was to evaluate the feasibility of these
      instruments as measured by administration time, time on task, and interruptions
      during test administration. METHODS: This was a prospective observational cross
      sectional study of a convenience sampling of adult patients presenting during
      March 2011 and February 2012 to one urban university-affiliated ED. Subjects were
      consenting non-critically ill, English-speaking patients over the age of 18 years
      without aphasia, dementia, mental retardation, or inability to communicate. The
      diagnostic test characteristics of the REALM-R, NVS, SILS, health numeracy, and
      physician gestalt were quantitatively assessed by using the short Test of
      Functional Health Literacy in Adults (S-TOFHLA). A score of 22 or less was the
      criterion standard for limited health literacy (LHL). RESULTS: A total of 435
      participants were enrolled, with a mean (+/-SD) age of 45 (+/-15.7) years, and
      18% had less than a high school education. As defined by an S-TOFHLA score of 22
      or less, the prevalence of LHL was 23.9%. In contrast, the NVS, REALM-R, and
      physician gestalt identified 64.8, 48.5, and 35% of participants as LHL,
      respectively. A normal NVS screen was the most useful test to exclude LHL, with a
      negative likelihood ratio of 0.04 (95% confidence interval [CI] = 0.01 to 0.17).
      When abnormal, none of the screening instruments, including physician gestalt,
      significantly increased the posttest probability of LHL. The NVS and REALM-R
      require 3 and 5 minutes less time to administer than the S-TOFHLA. Administration
      of the REALM-R is associated with fewer test interruptions. CONCLUSIONS: One
      quarter of these ED patients had marginal or inadequate health literacy. Among
      the brief screening instruments evaluated, a normal NVS result accurately reduced
      the probability of LHL, although it will identify two-thirds of ED patients as
      high risk for LHL. None of the brief screening instruments significantly
      increases the probability of LHL when abnormal.

PMID- 24673672
TI  - The effect of point-of-care ultrasonography on emergency department length of
      stay and computed tomography utilization in children with suspected appendicitis.
AB  - OBJECTIVES: The role of clinician-performed ultrasonography (US) for suspected
      appendicitis is unclear. Published data conclude that US has high specificity to
      rule in the diagnosis of appendicitis, with variable sensitivity to rule it out.
      Newer data suggest that point-of-care (POC) US may have similar test
      characteristics. Our objective was to evaluate the effect of POC US in children
      with suspected appendicitis and its effect on emergency department (ED) length of
      stay (LOS) and computed tomography (CT) utilization. METHODS: This was a
      prospective observational convenience sample of children with suspected
      appendicitis requiring imaging evaluation that adhered to the Standards for the
      Reporting of Diagnostic accuracy studies (STARD) criteria. Outcomes were
      determined by operative or pathology report in those who had appendicitis, and 3
      week phone follow-up in those patients who were nonoperative. Differences in ED
      LOS were analyzed by one-way analysis of variance (ANOVA) between patients who
      received dispositions after POC US, radiology US, or CT. Test performance
      characteristics were calculated for all imaging modalities. RESULTS: Among 150
      enrolled patients, 50 had appendicitis (33.3%). There were no missed cases of
      appendicitis in discharged patients at 3-week phone follow-up, nor negative
      laparotomies in those who went to the operating room. Those who had dispositions
      after POC US (n = 25) had a significantly decreased mean ED LOS (154 minutes, 95%
      confidence interval [CI] = 115 to 193 minutes) compared with those requiring
      radiology US (288 minutes, 95% CI = 257 to 319 minutes) or CT scan (487 minutes;
      95% CI = 434 to 540 minutes). Baseline CT rate was 44.2% (95% CI = 30.7% to
      57.7%) prior to study start and decreased to 27.3% (95% CI = 20.17% to 34.43%)
      during the study. CTs were avoided in four patients with conclusive POC US
      results and inconclusive radiology US results. The sensitivity, specificity,
      positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for POC US
      were 60% (95% CI = 46% to 72%), 94% (95% CI = 88% to 97%), 10 (95% CI = 4 to 23),
      and 0.4 (95% CI = 0.3 to 0.6). For radiology US they were 63% (95% CI = 48% to
      75%), 99% (95% CI = 94% to 99%), 94 (95% CI = 6 to 1,500), and 0.4 (95% CI = 0.3
      to 0.6); and for CT they were 83% (95% CI = 58% to 95%), 98% (95% CI = 85% to
      99%), 45 (95% CI = 3 to 707), and 0.2 (95% CI = 0.05 to 0.5). CONCLUSIONS: It may
      be feasible to reduce ED LOS and avoid CT scan when using POC US to evaluate
      children with suspected appendicitis. Test characteristics for POC US have high
      specificity to rule in appendicitis, similar to radiology US. Addition of POC US
      prior to sequential radiology imaging was safe, without missed cases of
      appendicitis or negative laparotomies.

PMID- 24673671
TI  - The microcirculation is preserved in emergency department low-acuity sepsis
      patients without hypotension.
AB  - OBJECTIVES: Microcirculatory dysfunction plays an important role in sepsis
      pathophysiology. Previous studies using sidestream dark-field (SDF) imaging have
      demonstrated microcirculatory flow abnormalities in patients with septic shock;
      however, the microcirculation is relatively unstudied in lower-acuity sepsis
      patients. The hypothesis was that patients with sepsis, but without hypotension,
      will demonstrate signs of flow abnormalities compared to noninfected control
      patients. METHODS: This was a prospective, observational study in a convenience
      sample of patients with sepsis and noninfected controls, conducted in three
      urban, tertiary care emergency departments (EDs) in the United States. Sepsis was
      defined as suspected infection plus two or more systemic inflammatory response
      syndrome (SIRS) criteria; those with hypotension were excluded. Noninfected
      controls were ED patients without infection and without SIRS criteria. SDF
      imaging was obtained in all study patients during ED evaluation. Recommended
      microcirculatory flow parameters were measured, and the difference in these
      measures between sepsis patients and noninfected controls were calculated. The
      authors also correlated microcirculatory flow parameters with patient variables,
      including serum lactate. RESULTS: A total of 106 patients were enrolled: 63 with
      sepsis and 43 noninfected controls. There were no differences in microcirculatory
      flow scores between sepsis patients and noninfected controls. Median
      microvascular flow index (MFI; with interquartile range [IQR] was 3.00 (IQR =
      2.73 to 3.00) in sepsis patients versus 2.93 (IQR = 2.73 to 3.00) in control
      patients (p = 0.33), and mean proportion of perfused small vessels (PPV) was
      91.5% (95% CI = 89.7% to 93.3%) versus 91.8% (95% CI = 89.7% to 93.9%), with a
      mean difference of 0.3% (95% CI = -2.5% to 3.1%; p = 0.84). Similarly, there were
      no significant differences in total vessel density, perfused vessel density, or
      heterogeneity index (HI). In the subset of infected patients for whom serum
      lactates were obtained (n % 37), MFI and PPV were negatively correlated with
      elevated serum lactate values: r = -0.32, p = 0.04; and r = -0.44, p < 0.01,
      respectively. CONCLUSIONS: Measureable microcirculatory flow abnormalities were
      not observed in patients with early sepsis in the absence of hypotension.
      However, microcirculatory abnormalities were correlated with elevated serum
      lactate in normotensive sepsis patients, supporting the notion that impaired
      microcirculatory flow is coupled with cellular distress.

PMID- 24673673
TI  - Procalcitonin as a marker of serious bacterial infections in febrile children
      younger than 3 years old.
AB  - OBJECTIVES: There is no perfectly sensitive or specific test for identifying
      young, febrile infants and children with occult serious bacterial infections
      (SBIs). Studies of procalcitonin (PCT), a 116-amino-acid precursor of the hormone
      calcitonin, have demonstrated its potential as an acute-phase biomarker for SBI.
      The objective of this study was to compare performance of serum PCT with
      traditional screening tests for detecting SBIs in young febrile infants and
      children. METHODS: This was a prospective, multicenter study on a convenience
      sample from May 2004 to December 2005. The study was conducted in four emergency
      departments (EDs): one pediatric ED and three EDs with pediatric units, all with
      academic faculty on staff. A total of 226 febrile children 36 months old or
      younger who presented to the four participating EDs and were evaluated for SBI by
      blood, urine, and/or cerebral spinal fluid (CSF) cultures were included. RESULTS:
      The test characteristics (with 95% confidence intervals [CIs]) of the white blood
      cell (WBC) counts including neutrophil and band counts were compared with PCT for
      identifying SBI. Thirty children had SBIs (13.3%, 95% CI = 8.85 to 17.70). Four
      (13.3%) had bacteremia (including one with meningitis), 18 (60.0%) had urinary
      tract infections (UTIs), and eight (26.6%) had pneumonia. Children with SBIs had
      higher WBC counts (18.6 * 10(9)  +/- 8.6 * 10(9) cells/L vs. 11.5 * 10(9)  +/-
      5.3 * 10(9) cells/L, p < 0.001), higher absolute neutrophil counts (ANCs; 10.6 *
      10(9)  +/- 6.7 * 10(9) cells/L vs. 5.6 * 10(9)  +/- 3.8 * 10(9) cells/L, p =
      0.009), higher absolute band counts (0.90 * 10(9)  +/- 1.1 * 10(9) cells/L vs.
      0.35 * 10(9)  +/- 0.6 * 10(9) cells/L, p = 0.009), and higher PCT levels (2.9 +/-
      5.6 ng/mL vs. 0.4 +/- 0.8 ng/mL, p = 0.021) than those without SBIs. In a
      multivariable logistic regression analysis, the absolute band count and PCT were
      the two screening tests independently associated with SBI, although the area
      under the receiver operating characteristic (ROC) curve for PCT was the largest
      (0.80, 95% CI = 0.71 to 0.89). CONCLUSIONS: Procalcitonin is a more accurate
      biomarker than traditional screening tests for identifying young febrile infants
      and children with serious SBIs. Further study on a larger cohort of young febrile
      children is required to definitively determine the benefit of PCT over
      traditional laboratory screening tests for SBIs.

PMID- 24673675
TI  - A randomized trial exploring the effect of a telephone call follow-up on care
      plan compliance among older adults discharged home from the emergency department.
AB  - OBJECTIVES: Older patients discharged from the emergency department (ED) have
      difficulty comprehending discharge plans and are at high risk of adverse
      outcomes. The authors investigated whether a postdischarge telephone call
      mediated intervention by a nurse would improve discharge care plan adherence,
      specifically by expediting post-ED visit physician follow-up appointments and/or
      compliance with medication changes. The second objectives were to determine if
      this telephone call intervention would reduce return ED visits and/or
      hospitalizations within 35 days of the index ED visit and to determine potential
      cost savings of this intervention. METHODS: This was a 10-week randomized,
      controlled trial among patients aged 65 and older discharged to home from an
      academic ED. At 1 to 3 days after each patient's index ED visit, a trained nurse
      called intervention group patients to review discharge instructions and assist
      with discharge plan compliance; placebo call group patients received a patient
      satisfaction survey call, while the control group patients were not called. Data
      collection calls occurred at 5 to 8 days and 30 to 35 days after the index ED
      visits for all three groups. Chi-square or Fisher's exact tests were performed
      for categorical data and the Kruskal-Wallis test examined group differences in
      time to follow-up. RESULTS: A total of 120 patients completed the study. Patients
      were 60% female and 72% white, with a mean age of 75 years (standard deviation
      [SD] +/- 7.58 years). Intervention patients were more likely to follow up with
      medical providers within 5 days of their ED visits than either the placebo or the
      control group patients (54, 20, and 37%, respectively; p = 0.04). All groups
      performed well in medication acquisition and comprehension of medication
      indications and dosage. There were no differences in return visits to the ED or
      hospital within 35 days of the index ED visit for intervention patients, compared
      to placebo or control group patients (22, 33, and 27%, respectively; p = 0.41).
      An economic analysis showed an estimated 70% chance that this intervention would
      reduce total costs. CONCLUSIONS: Telephone call follow-up of older patients
      discharged from the ED resulted in expedited follow-up for patients with their
      primary care physicians. Further study is warranted to determine if these results
      translate into improved patient outcomes, decreased return ED visits or hospital
      admissions, and cost savings resulting from this intervention.

PMID- 24673674
TI  - Validation of the Confusion Assessment Method for the Intensive Care Unit in
      older emergency department patients.
AB  - OBJECTIVES: In the emergency department (ED), health care providers miss delirium
      approximately 75% of the time, because they do not routinely screen for this
      syndrome. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)
      is a brief (<1 minute) delirium assessment that may be feasible for use in the
      ED. The study objective was to determine its validity and reliability in older ED
      patients. METHODS: In this prospective observational cohort study, patients aged
      65 years or older were enrolled at an academic, tertiary care ED from July 2009
      to February 2012. An emergency physician (EP) and research assistants (RAs)
      performed the CAM-ICU. The reference standard for delirium was a comprehensive
      (~30 minutes) psychiatrist assessment using the Diagnostic and Statistical Manual
      of Mental Disorders, Fourth Edition, Text Revision criteria. All assessments were
      blinded to each other and were conducted within 3 hours. Sensitivities,
      specificities, and likelihood ratios were calculated for both the EP and the RAs
      using the psychiatrist's assessment as the reference standard. Kappa values
      between the EP and RAs were also calculated to measure reliability. RESULTS: Of
      406 patients enrolled, 50 (12.3%) had delirium. The median age was 73.5 years old
      (interquartile range [IQR] = 69 to 80 years), 202 (49.8%) were female, and 57
      (14.0%) were nonwhite. The CAM-ICU's sensitivities were 72.0% (95% confidence
      interval [CI] = 58.3% to 82.5%) and 68.0% (95% CI = 54.2% to 79.2%) in the EP and
      RAs, respectively. The CAM-ICU's specificity was 98.6% (95% CI = 96.8% to 99.4%)
      for both raters. The negative likelihood ratios (LR-) were 0.28 (95% CI = 0.18 to
      0.44) and 0.32 (95% CI = 0.22 to 0.49) in the EP and RAs, respectively. The
      positive likelihood ratios (LR+) were 51.3 (95% CI = 21.1 to 124.5) and 48.4 (95%
      CI = 19.9 to 118.0), respectively. The kappa between the EP and RAs was 0.92 (95%
      CI = 0.85 to 0.98), indicating excellent interobserver reliability. CONCLUSIONS:
      In older ED patients, the CAM-ICU is highly specific, and a positive test is
      nearly diagnostic for delirium when used by both the EP and RAs. However, the CAM
      ICU's sensitivity was modest, and a negative test decreased the likelihood of
      delirium by a small amount. The consequences of a false-negative CAM-ICU are
      unknown and deserve further study.

PMID- 24673676
TI  - Risk factors for hospitalization after dog bite injury: a case-cohort study of
      emergency department visits.
AB  - OBJECTIVES: Dog bite injuries may result in pain, infection, emotional distress,
      dysfunction, and disfiguration, as well as lead to costly health care
      utilization, such as emergency department (ED) visits, rabies postexposure
      prophylaxis, and hospitalizations. Although clinical care guidelines exist, to
      our knowledge risk factors for hospitalization after a dog bite injury have not
      been examined quantitatively. Quantifying the magnitude of association between
      modifiable risk factors, such as infection, and hospitalization after a dog bite
      injury may guide intervention efforts, improve patient outcomes, and reduce
      unnecessary hospitalizations. METHODS: A case-cohort study was conducted to
      examine the association between the following risk factors and hospitalization:
      infection, complicated injury, host-defense abnormality, number of previous
      evaluations for the injury, and anatomic location of the bite. The case-cohort
      design was chosen because cases could be identified in a well-defined
      administrative cohort, medical record review was required for each study patient,
      and the risk ratio was the effect measure of interest. The cohort consisted of ED
      patients evaluated for dog bite injuries between January 1, 2000 and December 31,
      2011, at a large academic medical center. Cases were cohort members who were
      admitted as inpatients directly from the ED. From the cohort, a simple random
      sample was selected for the subcohort comparison group. Data on risk factors, the
      outcome, and covariates were collected from ED medical records. Logistic
      regression models, informed by directed acyclic graphs, were used to describe the
      relationship between each risk factor and hospitalization. Effect measure
      modification was examined by patient sex and race for the relationship between
      previous evaluation for the dog bite injury and hospitalization. RESULTS: Cases
      (n = 111) were more likely to be male, white, or insured by Medicaid than were
      members of the subcohort (n = 221). The most common type of complicated injury
      was tendon or ligament injury for cases and fracture for the subcohort. All
      factors evaluated were associated with increased risk of hospitalization after
      dog bite injury. Yet, infection at the time of ED visit (odds ratio [OR] = 7.8,
      95% confidence interval [CI] = 3.8 to 16.0) and injury to multiple anatomic
      locations (OR = 6.0, 95% CI = 1.2 to 30.9) were associated with the largest
      relative risks of hospitalization. For every three ED visits for infected dog
      bites, one resulted in hospitalization. Having had one or more prior evaluations
      for the dog bite injury was associated with a lower risk of hospitalization for
      females than males and for whites than nonwhites. CONCLUSIONS: This study
      provides a unique, quantitative examination of risk factors for hospitalization
      after dog bite injury. The relative risk of hospitalization associated with each
      factor was substantial. The strongest association was for a modifiable risk
      factor, infection. This finding may inform best practices for initial care of
      patients with dog bite injuries and the development of novel protocols for
      following patients to reduce infections and subsequent hospitalizations.

PMID- 24673681
TI  - Phylogeography in continuous space: coupling species distribution models and
      circuit theory to assess the effect of contiguous migration at different climatic
      periods on genetic differentiation in Busseola fusca (Lepidoptera: Noctuidae).
AB  - Current population genetic models fail to cope with genetic differentiation for
      species with large, contiguous and heterogeneous distribution. We show that in
      such a case, genetic differentiation can be predicted at equilibrium by circuit
      theory, where conductance corresponds to abundance in species distribution models
      (SDMs). Circuit-SDM approach was used for the phylogeographic study of the
      lepidopteran cereal stemborer Busseola fuscaFuller (Noctuidae) across sub-Saharan
      Africa. Species abundance was surveyed across its distribution range. SDMs were
      optimized and selected by cross-validation. Relationship between observed
      matrices of genetic differentiation between individuals, and between matrices of
      resistance distance was assessed through Mantel tests and redundancy discriminant
      analyses (RDAs). A total of 628 individuals from 130 localities in 17 countries
      were genotyped at seven microsatellite loci. Six population clusters were found
      based on a Bayesian analysis. The eastern margin of Dahomey gap between East and
      West Africa was the main factor of genetic differentiation. The SDM projections
      at present, last interglacial and last glacial maximum periods were used for the
      estimation of circuit resistance between locations of genotyped individuals. For
      all periods of time, when using either all individuals or only East African
      individuals, partial Mantel r and RDA conditioning on geographic distance were
      found significant. Under future projections (year 2080), partial r and RDA
      significance were different. From this study, it is concluded that analytical
      solutions provided by circuit theory are useful for the evolutionary management
      of populations and for phylogeographic analysis when coalescence times are not
      accessible by approximate Bayesian simulations. 

PMID- 24673682
TI  - Attention-deficit/hyperactivity disorder in young French male prisoners.
AB  - While forensic studies have reported higher than community rates of mental
      disorders in imprisoned populations, few studies have focused on attention
      deficit/hyperactivity disorder (ADHD) in these subjects. The aim of this study
      was to investigate ADHD prevalence among young French male prisoners. A specific
      diagnostic interview (Conners' Adult ADHD Diagnostic Interview for DSM-IV,
      CAADID) was used. Correlations between ADHD, subsyndromal ADHD, and criminal
      features were investigated. 11% of young male prisoners among 93 male subjects
      aged 18-35 years met the criteria for actual ADHD, and 17% met those for
      childhood ADHD. Considering ADHD and subsyndromal ADHD, prevalence was about 43%
      in adulthood. ADHD and subsyndromal ADHD in adulthood were significantly
      associated with a higher number of imprisonments and a younger age at first
      arrest. It could be advisable to better identify subjects with ADHD symptoms
      among prison populations.

PMID- 24673683
TI  - Defective antiviral CD8 T-cell response and viral clearance in the absence of c
      Jun N-terminal kinases.
AB  - The c-Jun N-terminal kinase (JNK) signalling pathway appears to act as a critical
      intermediate in the regulation of lymphocyte activation and proliferation. The
      majority of studies on the importance of JNK are focused on its role in T helper
      responses, with very few reports addressing the mechanisms of JNK in governing
      CD8 T-cell-mediated immunity. By using a well-defined mousepox model, we
      demonstrate that JNK is involved in CD8(+) T-cell-mediated antiviral responses.
      Deficiency of either JNK1 or JNK2 impaired viral clearance, subsequently
      resulting in an increased susceptibility to ectromelia virus in resistant mice.
      The impairment of CD8 responses in JNK-deficient mice was not directly due to an
      inhibition of effector T-cell expansion, as both JNK1 and JNK2 had limited effect
      on the activation-induced cell death of CD8(+) T cells, and only JNK2-deficient
      mice exhibited a significant change in CD8(+) T-cell proliferation after acute
      ectromelia virus infection. However, optimal activation of CD8(+) T cells and
      their effector functions require signals from both JNK1 and JNK2. Our results
      suggest that the JNK pathway acts as a critical intermediate in antiviral
      immunity through regulation of the activation and effector function of CD8(+) T
      cells rather than by altering their expansion. 

PMID- 24673684
TI  - Avian extraintestinal Escherichia coli exhibits enterotoxigenic-like activity in
      the in vivo rabbit ligated ileal loop assay.
AB  - Avian pathogenic Escherichia coli (APEC) strains harbor a number of virulence
      genes and cause extraintestinal diseases, such as septicemia, swollen-head
      syndrome, salpingitis, and omphalitis in poultry. APEC strains are not known to
      cause intestinal diseases. Herein, for the first time, it is reported that APEC
      strains were able to induce an enterotoxigenic-like effect in rabbit ligated
      ileal loops. Strain SEPT362 caused cell detachment of the intestinal villi, which
      also showed a flattened and wilted appearance, but the integrity of the tight
      junctions was maintained. Additionally, this strain did not adhere to enterocytes
      in vivo, although adhesin encoding genes ( fimH, csgA, lpfA2-3, and ECP) were
      present while other lpfA types, sfa, afa, papC, and ral genes were not. This
      enterotoxigenic-like activity was conserved after thermal treatment of the
      supernatant at 65 degrees C but not at 100 degrees C. Moreover, experiments based
      on filtering with different molecular weight cut-off (MWCO) pore sizes
      demonstrated that the component associated with the observed biological effect
      has a molecular weight >100 kDa. Blast search and polymerase chain reaction
      assays for known E. coli virulence factors showed that strain SEPT362 harbors the
      gene encoding for the toxin EAST-1 and the serine protease autotransporter
      (SPATE) Tsh, but is negative for genes encoding for the toxins LT-I, STh, STp,
      Stx1, Stx2, CNF-1, CNF-2, CDT and the SPATEs Sat, Pic, Vat, SigA, SepA, EatA,
      EspP, or EspC. A cloned copy of the tsh gene in E. coli K-12 was also tested and
      was shown to have an enterotoxic effect. These results suggest that APEC might
      induce fluid accumulation in the rabbit gut. The Tsh autotransporter seems to be
      one of the factors associated with this phenotype.

PMID- 24673685
TI  - Chromoblastomycosis: demonstration of abundant microorganisms on microscopy of a
      scaly crust following intralesional corticosteroids.

PMID- 24673686
TI  - cDNA cloning and expression characterization of serum transferrin gene from
      oriental weatherfish Misgurnus anguillicaudatus.
AB  - In this study, the cDNA coding serum transferrin (stf) of Misgurnus
      anguillicaudatus (mastf) was cloned. mastf cDNA is composed of 2326 bp with a
      2007 bp open reading frame encoding 668 amino acids. The deduced Mastf protein
      consists of a signal peptide, two lobes (N and C-lobes) and signature motifs of
      transferrin (Tf) family. The results of tissue distribution indicated that mastf
      mRNA was predominantly expressed in the liver. The results indicate that the
      mastf expression increased significantly in liver, blood, spleen and head kidney
      after the challenge with Aeromonas sobria, acting as a positive acute protein,
      suggesting that mastf is related to the immune response. The cloning and
      expression analysis of mastf further demonstrates the evolutionary conservation
      of Stf and immune function in vertebrates. 

PMID- 24673687
TI  - Parent and family stress factors predict health-related quality in pediatric
      patients with new-onset epilepsy.
AB  - OBJECTIVE: To examine the influence of parent and family general and epilepsy
      related stress on longitudinal generic and epilepsy-specific health-related
      quality of life (HRQOL) for children with new-onset epilepsy, while controlling
      for demographic characteristics, disease factors, and antiepileptic drug (AED)
      adherence. METHODS: This prospective, longitudinal study included 124 children
      with new-onset epilepsy (mean age 7.2 years, standard deviation [SD] 2.9 years).
      Parents completed questionnaires on parenting stress, perceived stigma, fears and
      concerns, and HRQOL at 1, 13, and 25 months after diagnosis. Adherence to AEDs
      was assessed using electronic monitors. A medical chart review was conducted at
      each visit to obtain seizure and side effect data. RESULTS: Higher levels of
      general and epilepsy-specific parent and family stress, fears and concerns, and
      perceived stigma negatively affected child generic and epilepsy-specific HRQOL,
      above and beyond disease and demographic factors. General parenting and family
      stress affected child generic and epilepsy-specific HRQOL more in the first year
      of disease management than at 2 years after diagnosis. Higher fears and concerns
      predicted higher epilepsy-specific HRQOL at 13 months postdiagnosis, whereas 2
      years postdiagnosis, higher fears and concerns predicted lower epilepsy-specific
      HRQOL. Several demographic (i.e., age) and disease-related variables (i.e., side
      effects and AED adherence) influenced child generic and epilepsy-specific HRQOL.
      Although some findings were consistent across generic and epilepsy-specific HRQOL
      measures, others were unique. SIGNIFICANCE: Modifiable parent factors (i.e.,
      general and disease-specific parent and family stress, perceived stigma) impact
      HRQOL for children with new-onset epilepsy differently over the first 2 years
      postdiagnosis. Psychosocial interventions to improve HRQOL within the first year
      postdiagnosis should address parenting and family stress, overall coping, and
      anticipatory guidance on managing epilepsy. Interventions targeting adherence,
      perceived stigma, and fears and concerns could improve HRQOL. Promoting parent
      management of stress, fears/concerns, and perceived stigma may lead to improved
      child HRQOL outcomes. A PowerPoint slide summarizing this article is available
      for download in the Supporting Information section here.

PMID- 24673688
TI  - Automating the processing steps for obtaining bone tissue-engineered substitutes:
      from imaging tools to bioreactors.
AB  - Bone diseases and injuries are highly incapacitating and result in a high demand
      for tissue substitutes with specific biomechanical and structural features.
      Tissue engineering has already proven to be effective in regenerating bone
      tissue, but has not yet been able to become an economically viable solution due
      to the complexity of the tissue, which is very difficult to be replicated,
      eventually requiring the utilization of highly labor-intensive processes. Process
      automation is seen as the solution for mass production of cellularized bone
      tissue substitutes at an affordable cost by being able to reduce human
      intervention as well as reducing product variability. The combination of tools
      such as medical imaging, computer-aided fabrication, and bioreactor technologies,
      which are currently used in tissue engineering, shows the potential to generate
      automated production ecosystems, which will, in turn, enable the generation of
      commercially available products with widespread clinical application. 

PMID- 24673690
TI  - Technical and biological complications of single-molar implant restorations.
AB  - OBJECTIVES: Retrospective evaluation of the biological and technical
      complications in implant-supported single-tooth molar restorations performed in a
      private practice after functional periods of >=4 years. MATERIAL AND METHODS:
      Sixty-five patients (34 females, age 51.7 +/- 10.6 years) with 112 implants
      received annual follow-up examinations and participated in a maintenance program.
      The survival (in situ) and success (complication-free) rates of implants and
      superstructures were evaluated. Time-dependent peri-implantitis rates were
      calculated, and the influencing factors were identified using a multiple Cox
      regression. RESULTS: The implant survival rate was 100%. Three of 112 crowns
      required replacement (prosthetic survival rate = 98.1%). Thirty technical
      complications were observed: loss of retention (16), ceramic fracture (10), and
      screw loosening (4). The success rate of the superstructures was 79.0% after 7
      years. Overall, 9.2% of the patients developed peri-implantitis (probing depth
      >=5 mm, BOP, suppuration, bone loss >=3.5 mm); (smokers: 41.6%, non-smokers:
      1.8%). After 7 years, the time-dependent implant success rate (free of peri
      implantitis) was 100% for non-smokers and 58.6% for smokers. Multiple analysis
      showed a significant effect of smoking (hazard ratio, 19.5; P = 0.008) on peri
      implantitis. CONCLUSIONS: Implants with cemented single-tooth restorations in the
      molar region constitute a reliable treatment in private practice. Smokers have a
      significantly increased peri-implantitis rate.

PMID- 24673691
TI  - Updating the International Standards for Tuberculosis Care. Entering the era of
      molecular diagnostics.
AB  - The International Standards for Tuberculosis Care, first published in 2006
      (Lancet Infect Dis 2006;6:710-725.) with a second edition in 2009 (
      www.currytbcenter.ucsf.edu/international/istc_report ), was produced by an
      international coalition of organizations funded by the United States Agency for
      International Development. Development of the document was led jointly by the
      World Health Organization and the American Thoracic Society, with the aim of
      promoting engagement of all care providers, especially those in the private
      sector in low- and middle-income countries, in delivering high-quality services
      for tuberculosis. In keeping with World Health Organization recommendations
      regarding rapid molecular testing, as well as other pertinent new
      recommendations, the third edition of the Standards has been developed. After
      decades of dormancy, the technology available for tuberculosis care and control
      is now rapidly evolving. In particular, rapid molecular testing, using devices
      with excellent performance characteristics for detecting Mycobacterium
      tuberculosis and rifampin resistance, and that are practical and affordable for
      use in decentralized facilities in low-resource settings, is being widely
      deployed globally. Used appropriately, both within tuberculosis control programs
      and in private laboratories, these devices have the potential to revolutionize
      tuberculosis care and control, providing a confirmed diagnosis and a
      determination of rifampin resistance within a few hours, enabling appropriate
      treatment to be initiated promptly. Major changes have been made in the standards
      for diagnosis. Additional important changes include: emphasis on the recognition
      of groups at increased risk of tuberculosis; updating the standard on
      antiretroviral treatment in persons with tuberculosis and human immunodeficiency
      virus infection; and revising the standard on treating multiple drug-resistant
      tuberculosis. 

PMID- 24673689
TI  - "Pointsource" delivery of a photosensitizer drug and singlet oxygen: eradication
      of glioma cells in vitro.
AB  - We describe a pointsource sensitizer-tipped microoptic device for the eradication
      of glioma U87 cells. The device has a mesoporous fluorinated silica tip which
      emits singlet oxygen molecules and small quantities of pheophorbide sensitizer
      for additional production of singlet oxygen in the immediate vicinity. The
      results show that the device surges in sensitizer release and photokilling with
      higher rates about midway through the reaction. This was attributed to a self
      amplified autocatalytic reaction where released sensitizer in the extracellular
      matrix provides positive feedback to assist in the release of additional
      sensitizer. The photokilling of the glioma cells was analyzed by global toxicity
      and live/dead assays, where a killing radius around the tip with ~0.3 mm
      precision was achieved. The implication of these results for a new PDT tool of
      hard-to-resect tumors, e.g. in the brain, is discussed. 

PMID- 24673692
TI  - Multidrug-resistant tuberculosis. Recommendations for reducing risk during travel
      for healthcare and humanitarian work.
AB  - Healthcare and humanitarian workers who travel to work where the incidence of
      multidrug-resistant tuberculosis (MDR TB) is high and potential transmission may
      occur are at risk of infection and disease due to these resistant strains.
      Transmission occurs due to inadequate transmission control practices and the
      inability to provide timely and accurate diagnosis and treatment of persons with
      MDR TB. Patients risk exposure if active TB is unrecognized in workers after they
      return to lower-risk settings. Guidance for risk reduction measures for workers
      in high-risk areas is limited, and no studies confirm the efficacy of treatment
      regimens for latent TB infection due to MDR TB. Bacille Calmette-Guerin (BCG)
      vaccination decreases the risk of active TB and possibly latent infection. IFN
      gamma release assays differentiate TB infection from BCG vaccination effect. A
      series of risk reduction measures are provided as a potential strategy. These
      measures include risk reductions before travel, including risk assessment, TB
      screening, education, respirator fit testing, and BCG vaccination. Measures
      during travel include use of respirators in settings where this may not be common
      practice, transmission control practices, triaging of patients with consistent
      symptoms, providing education for good cough etiquette, and provision of care in
      well-ventilated areas, including open air areas. Risk reduction measures after
      return include TB screening 8 to 10 weeks later and recommendations for
      management of latent TB infection in areas where the likelihood of MDR TB
      exposure is high. 

PMID- 24673693
TI  - Quality tuberculosis care. All should adopt the new international standards for
      tuberculosis care.

PMID- 24673694
TI  - Occupational screening for tuberculosis. A testing time for interferon-gamma
      release assays.

PMID- 24673695
TI  - Practice guidelines, clinical trials, and unexpected results in cystic fibrosis.

PMID- 24673696
TI  - The global burden of respiratory disease.
AB  - The Forum of International Respiratory Societies has released a report entitled
      Respiratory Disease in the World: Realities of Today-Opportunities for Tomorrow.
      The report identifies five conditions that primarily contribute to the global
      burden of respiratory disease (asthma, chronic obstructive pulmonary disease,
      acute respiratory infections, tuberculosis, and lung cancer), and offers an
      action plan to prevent and treat those diseases. It describes the staggering
      magnitude of the global burden of lung disease: hundreds of millions of people
      suffer and four million people die prematurely from respiratory diseases each
      year. The situation is not hopeless, because most major respiratory illnesses are
      avoidable. Much of the disease burden can be mitigated by reducing exposure to
      indoor and outdoor air pollution, restraining tobacco use, and relieving urban
      overcrowding. Implementation of the strategies described in the Forum of
      International Respiratory Societies respiratory diseases report would have a
      profound effect on respiratory health, reduce economic costs, and enhance health
      equality in the world. 

PMID- 24673697
TI  - Lung disease in a global context. A call for public health action.
AB  - As described in a recently released report of the Forum of International
      Respiratory Societies, four of the leading causes of death in the world are
      chronic obstructive pulmonary disease, acute respiratory tract infections, lung
      cancer, and tuberculosis. A fifth, asthma, causes enormous global morbidity. Not
      enough progress has been made in introducing new therapies and reducing disease
      burden for these illnesses in the last few decades, despite generous investments
      and some notable progress in biomedical research. Four external and modifiable
      drivers are responsible for a substantial percentage of the disease burden
      represented by the major lung diseases: tobacco, outdoor air pollution, household
      air pollution, and occupational exposures to lung toxins. Especially in low- and
      middle-income countries, but in highly developed economies as well, pressures for
      economic development and lax regulation are contributing to the continued
      proliferation of these drivers. Public health approaches to the most common lung
      diseases could have enormous effects on reducing morbidity and mortality. There
      must be increased advocacy from and mobilization of civil society to bring
      attention to the drivers of lung diseases in the world. The World Health
      Organization should negotiate accords similar to the Framework Convention on
      Tobacco Control to address air pollution and occupational exposures. Large
      increases in funding by government agencies and nongovernmental organizations
      around the world are needed to identify technologies that will reduce health
      risks while allowing populations to enjoy the benefits of economic development.
      This paradigm, focused more on public health than on individual medical
      treatment, has the best chance of substantial reduction in the burden of lung
      disease around the world in the next several years. 

PMID- 24673700
TI  - Patient, physician, and researcher. My life's journey with recurrent spontaneous
      pneumothorax.

PMID- 24673699
TI  - Recognizing, naming, and measuring a family intensive care unit syndrome.
AB  - Most major decisions in the intensive care unit (ICU) regarding goals of care are
      shared by clinicians and someone other than the patient. Multicenter clinical
      trials focusing on improved communication between clinicians and these surrogate
      decision makers have not reported consistently improved outcomes. We suggest that
      acquired maladaptive reasoning may contribute importantly to failure of the
      intervention strategies tested to date. Surrogate decision makers often suffer
      significant psychological morbidity in the form of stress, anxiety, depression,
      and post-traumatic stress disorder. Family members in the ICU also suffer
      cognitive blunting and sleep deprivation. Their decision-making abilities are
      eroded by anticipatory grief and cognitive biases, while personal and family
      conflicts further impact their decision making. We propose recognizing a family
      ICU syndrome to describe the morbidity and associated decision-making impairment
      experienced by many family members of patients with acute critical illness (in
      the ICU) and chronic critical illness (in the long-term, acute care hospital).
      Research rigorously using models of compromised decision making may help
      elucidate both mechanisms of impairment and targets for intervention. Better
      quantifying compromised decision making and its relationship to poor outcomes
      will allow us to formulate and advance useful techniques. The use of decision
      aids and improving ICU design may provide benefit now and in the near future. In
      measuring interventions targeting cognitive barriers, clinically significant
      outcomes, such as time to decision, should be considered. Statistical approaches,
      such as survival models and rank statistic testing, will increase our power to
      detect differences in our interventions. 

PMID- 24673698
TI  - Inhaled antibiotics for lower airway infections.
AB  - Inhaled antibiotics have been used to treat chronic airway infections since the
      1940s. The earliest experience with inhaled antibiotics involved aerosolizing
      antibiotics designed for parenteral administration. These formulations caused
      significant bronchial irritation due to added preservatives and nonphysiologic
      chemical composition. A major therapeutic advance took place in 1997, when
      tobramycin designed for inhalation was approved by the U.S. Food and Drug
      Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic
      Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in
      CF and the availability of dry powder antibiotic formulations, there has been a
      growing interest in the use of inhaled antibiotics in other lower respiratory
      tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia,
      chronic obstructive pulmonary disease, mycobacterial disease, and in the post
      lung transplant setting over the past decade. Antibiotics currently marketed for
      inhalation include nebulized and dry powder forms of tobramycin and colistin and
      nebulized aztreonam. Although both the U.S. Food and Drug Administration and
      European Medicines Agency have approved their use in CF, they have not been
      approved in other disease areas due to lack of supportive clinical trial
      evidence. Injectable formulations of gentamicin, tobramycin, amikacin,
      ceftazidime, and amphotericin are currently nebulized "off-label" to manage non
      CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections,
      ventilator-associated pneumonia, and post-transplant airway infections. Future
      inhaled antibiotic trials must focus on disease areas outside of CF with sample
      sizes large enough to evaluate clinically important endpoints such as
      exacerbations. Extrapolating from CF, the impact of eradicating organisms such as
      P. aeruginosa in non-CF bronchiectasis should also be evaluated. 

PMID- 24673701
TI  - Persistent alkalosis in a 12-year-old with medulloblastoma.

PMID- 24673702
TI  - Systolic blood pressure variation during mechanical ventilation.

PMID- 24673703
TI  - Reply: hypotheses for the decrease in the ipsilateral and contralateral lung
      ventilation after a pleural aspiration.

PMID- 24673704
TI  - Lung reaeration and reventilation after aspiration of pleural effusions: a study
      using electrical impedance tomography.

PMID- 24673705
TI  - External fixation of a subglottic tracheal silicone stent.

PMID- 24673706
TI  - Recovery from mitomycin-induced pulmonary arterial hypertension.

PMID- 24673708
TI  - Osteonecrosis of the jaw and renal safety in patients with newly diagnosed
      multiple myeloma: Medical Research Council Myeloma IX Study results.
AB  - Bisphosphonates are recommended in patients with osteolytic lesions secondary to
      multiple myeloma. We report on the safety of bisphosphonate therapy with long
      term follow-up in the Medical Research Council Myeloma IX study. Patients with
      newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg
      intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus
      chemotherapy. Among 1960 patients (5.9-year median follow-up), both
      bisphosphonates were well tolerated. Acute renal failure events were similar
      between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence plateaued
      thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ)
      was low, but higher with ZOL (ZOL 3.7% vs. CLO 0.5%; P < 0.0001). ONJ events were
      generally low grade and most occurred between 8 and 30 months (median time to
      ONJ, 23.7 months). Among 10 patients with ONJ recovery data, four patients in the
      ZOL group completely recovered, two patients improved, and three patients
      experienced no improvement; one CLO patient experienced no improvement. Dental
      surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal
      adverse events was similar for ZOL and CLO. ONJ incidence remained low and was
      lower with CLO compared to ZOL. We have seen no further ONJ cases to date.

PMID- 24673710
TI  - Infantile perianal pyramidal protrusions identified in adult women.

PMID- 24673711
TI  - Ordered-mesoporous-carbon-bonded cobalt phthalocyanine: a bioinspired catalytic
      system for controllable hydrogen peroxide activation.
AB  - The chemistry of enzymes presents a key to understanding the catalysis in the
      world. In the pursuit of controllable catalytic oxidation, researchers make
      extensive efforts to discover and develop functional materials that exhibit
      various properties intrinsic to enzymes. Here we describe a bioinspired catalytic
      system using ordered-mesoporous-carbon (OMC)-bonded cobalt
      tetraaminophthalocyanine (CoTAPc-OMC) as a catalyst that could mimic the space
      environment and reactive processes of metalloporphyrin-based heme enzymes and
      employing linear dodecylbenzenesulfonate as the fifth ligands to control the
      activation of H2O2 toward the peroxidase-like oxidation. The generation of
      nonselective free hydroxyl radicals was obviously inhibited. In addition,
      functional modification of OMC has been achieved by a moderate method, which can
      reduce excessive damage to the structure of OMC. Because of its favorable and
      tunable pore texture, CoTAPc-OMC provides a suitable interface and environment
      for the accessibility and oxidation of C.I. Acid Red 1, the model compound, and
      exhibits significantly enhanced catalytic activity and sufficient stability for
      H2O2 activation. The high-valent cobalt oxo intermediates with high oxidizing
      ability have been predicted as the acceptable active species, which have been
      corroborated by the results from the semiempirical quantum-chemical PM6
      calculations. 

PMID- 24673712
TI  - Enteric-coated mycophenolate sodium: an update.

PMID- 24673713
TI  - Cyclosporine A and tacrolimus combined with enteric-coated mycophenolate sodium
      influence the plasma mycophenolic acid concentration - a randomised controlled
      trial in Chinese live related donor kidney transplant recipients.
AB  - OBJECTIVE: To observe the different concentrations of mycophenolic acid (MPA)
      during the early post-transplant phase for various combinations of cyclosporine A
      (CsA) and tacrolimus (Tac) with enteric-coated mycophenolate sodium (EC-MPS).
      METHOD: A total of 42 Chinese adults receiving live related donor kidney
      transplants were studied. All received a triple immunosuppressive regimen of EC
      MPS, CsA/Tac and corticosteroids and were divided randomly into CsA (n = 21) and
      Tac (n = 21) combination groups. The dosage of EC-MPS was the same (1440 mg/day)
      in the two groups. The MPA concentration was evaluated with an enzyme-multiplied
      immunoassay technique (EMIT) and the pharmacokinetic characteristics were
      investigated in both groups. RESULTS: The mean maximum plasma concentrations
      (Cmax ) of MPA in the CsA and Tac groups were 11.365 +/- 9.522 and 9.748 +/-
      7.523 MUg/ml, respectively (p = 0.137). The maximum times to Cmax (Tmax ) were
      2.54 +/- 1.53 and 2.67 +/- 1.08 h, respectively (p = 0.341). The mean MPA 12-h
      areas under the curve (MPA-AUC0-12 h ) were 59.463 +/- 16.252 and 77.535 +/-
      33.615 MUg h/ml (p = 0.003) and the mean residence times (MRT) were 3.71 +/-
      0.829 and 3.928 +/- 0.923 h (p = 0.038). CONCLUSION: Combined with the same EC
      MPS dosage (1440 mg/day), the MPA-AUC0-12 of the Tac group was higher than that
      of the CsA group, and the Tac group had a longer MRT after kidney
      transplantation. Our data indicate that the concentration of MPA should be
      monitored in clinical therapy when EC-MPS is combined with different calcineurin
      inhibitors to reduce acute allograft rejection and avoid adverse events.

PMID- 24673714
TI  - Which is more suitable for kidney transplantation at the early post
      transplantation phase in China - low dosing or standard dosing of enteric-coated
      mycophenolate sodium?
AB  - AIMS: To investigate the pharmacokinetics of enteric-coated mycophenolate sodium
      (EC-MPS) and the clinical outcome in kidney transplant recipients in the early
      post-transplantation phase. Then explain which regimen is more suitable for
      Chinese renal transplant recipients. METHODOLOGY: In total, 60 de novo kidney
      transplant recipients treated with tacrolimus and steroids were randomised to
      receive EC-MPS at standard dose (SD; 1440 mg/day; n = 28) or low dose (LD; 1080
      mg/day; n = 32). Efficacy parameters, safety and tolerability were assessed over
      a 6-month study period. Full mycophenolic acid (MPA) areas under the curve (AUCs)
      were completed on days 3 and 5, whereas a three-point limited sampling strategy
      (LSS) was utilised for MPA AUC assessments at 2 weeks and months 1, 3 and 6 (the
      LSS for three-time-point MPA AUC 0-12 h (mg h/l) = 15.99 + 0.87C1 h  + 0.68C2 h 
      + 7.85C4 h ; r(2)  = 0.8670. RESULTS: The mean AUC levels at day 3 and day 5 in
      the SD group were significantly higher than in the LD group (57.4 mg.h/l vs. 38.2
      mg.h/l and 59.3 mg.h/l vs. 44.8 mg.h/l, respectively, p < 0.01). There was a
      trend for fewer clinically diagnosed acute rejections in the SD group vs. the LD
      group at 6 months (7.1% vs. 12.5%). This trend was also present when acute
      rejection was analysed as biopsy-proven cases. There were significantly more
      acute rejections (all definitions) in patients with MPA AUC levels < 30 mg.h/l
      compared with those with MPA AUC levels >= 30 mg.h/l within 6 months (p < 0.05).
      Renal function, incidence of infection and haematological disorders were not
      significantly different in either study group. CONCLUSIONS: Early adequate MPA
      exposure in renal transplant recipients can be achieved with a higher starting
      dose. In addition, a SD regimen was as well-tolerated as a LD regimen.
      Furthermore, early adequate MPA exposure significantly lowered the rate of acute
      rejection without compromising safety and tolerability.

PMID- 24673715
TI  - Efficacy and safety of enteric-coated mycophenolate sodium in patients with de
      novo and maintenance renal transplantation.
AB  - AIMS: To evaluate the efficacy and safety of enteric-coated mycophenolate sodium
      (EC-MPS) in renal transplant patients treated de novo and for maintenance.
      METHODS: The efficacy and safety data of EC-MPS in renal transplant patients
      treated de novo and for maintenance in our hospital from July 2009 to March 2013
      were reviewed. RESULTS: Thirty-one patients treated with EC-MPS de novo were
      included: there were 16 male and 15 female patients. The acute allograft
      rejection rate was 12.9% (4/31) and pneumonia occurred in 25.8% patients (8/31);
      the allograft survival rate was 96.7% (30/31) with a patient survival rate of
      96.7% (30/31). Gastrointestinal side effects occurred in four patients (12.9%).
      Only one patient discontinued EC-MPS and treatment was converted to bredinin
      because of gastrointestinal intolerance. Thirty-nine patients receiving
      mycophenolate mofetil (MMF) de novo treatment served as a control group. Five
      (13.2%) of 38 patients developed serious acute rejection and 10 patients (26.3%)
      had pulmonary infection. Eight (21.1%) patients suffered abdominal distention,
      diarrhoea and other gastrointestinal adverse reactions; the symptoms improved
      significantly after treatment change to mizoribine. Compared with the MMF de novo
      group, the allograft function, blood cell counts and urine protein were similar
      in the EC-MPS de novo treatment group. The incidence of gastrointestinal side
      effects was obviously lower in the EC-MPS group than in the MMF group, and there
      was no difference in serious acute rejection and pulmonary infection between the
      groups. The study also included 23 renal transplantation maintenance patients who
      suffered from chronic diarrhoea and treatment was changed to EC-MPS treatment.
      This change to EC-MPS was at 77 months after transplantation. The
      gastrointestinal symptoms improved significantly in 21 patients after conversion.
      Compared with the results at 1 week, no obvious deterioration in serum
      creatinine, cystatin or estimated glomerular filtration rate was found at 1, 3
      and 12 months after the change. In addition, there was no marked decline in blood
      cell counts and no significant increase in urine protein. CONCLUSION: The outcome
      of EC-MPS treatment in clinical practice of de novo kidney transplant patients
      was good, with high patient and graft survivals. In maintenance patients it
      induced an improvement in gastrointestinal side effects and a stable allograft
      function.

PMID- 24673716
TI  - A single-centre, open-label, prospective study of an initially short-term
      intensified dosing regimen of enteric-coated mycophenolate sodium with reduced
      cyclosporine A exposure in Chinese live-donor kidney transplant recipients.
AB  - AIMS: The nephrotoxicity of cyclosporine A (CsA) accounts for dysfunction of
      kidney allografts in the clinic. Short-term intensified dosing using enteric
      coated mycophenolate sodium (EC-MPS) may facilitate CsA sparing after kidney
      transplantation without compromising safety. METHODS: In a 12-month, single
      centre open-label prospective trial, 180 de novo live-donor kidney transplant
      recipients at low-immunological risk were randomised to a low-dose cyclosporine
      group which received a low dose of cyclosporine, short-term intensified EC-MPS
      dosing (2160 mg/day to week 6, 1440 mg/day thereafter) and corticosteroids or a
      standard-dose cyclosporine group which received a standard dose of cyclosporine,
      standard EC-MPS dosing (1440 mg/day) and corticosteroids. The primary end-point
      [treatment failure including biopsy-proven acute rejection (BPAR), graft loss,
      death], secondary end-point and adverse events were monitored. RESULTS: The
      primary end-point (treatment failure) occurred in 13.3% (12/90) of the low-dose
      cyclosporine group and 16.7% (15/90) of the standard-dose cyclosporine group (p =
      0.53) (difference -3.4%, 95% confidence interval -11.7% to 7.5%, based on a
      noninferiority margin of 20%). BPAR occurred in 11.1% and 13.3% of patients in
      the low-dose cyclosporine group and standard-dose cyclosporine group,
      respectively (p = 0.65). The estimated glomerular filtration rate, as calculated
      by the Cockcroft-Gault formula, was similar at 12 months after transplantation
      (low-dose cyclosporine group 63 +/- 19 ml/min/1.73 m(2) and standard-dose
      cyclosporine group 59 +/- 15 ml/min/1.73 m(2) ; p = 0.43). The levels of serum
      creatinine and occurrence of adverse events between the two groups were not
      statistically different. CONCLUSIONS: A regimen of early intensified EC-MPS
      dosing permits low-dose cyclosporine in live-donor kidney transplant patients at
      low-immunological risk without compromising efficacy at 12 months' follow-up.

PMID- 24673717
TI  - Lower dosing of enteric-coated mycophenolate sodium (Myfortic) can achieve target
      mycophenolic acid exposure rapidly in most Chinese renal transplant patients: a
      pilot study.
AB  - AIMS: There are few pharmacokinetic data for enteric-coated mycophenolate sodium
      (EC-MPS) in Chinese kidney transplant recipients. Previously, we demonstrated
      that patients with 540 mg EC-MPS reached target exposure on day 4 after
      transplantation. The aim of this study was further to confirm that mycophenolic
      acid (MPA) delivery with a daily total dose 1080 mg EC-MPS is adequate during the
      early-phase posttransplantation and preliminarily assess the pharmacokinetics
      after a single dose and multiple doses of EC-MPS in Chinese live-donor kidney
      transplant recipients. METHODS: Twelve patients (eight men and four women, mean
      age 41.3 +/- 6.78 years) treated with EC-MPS, cyclosporine and corticosteroids
      were included in this study. Patients received a single oral dose of EC-MPS 540
      mg, then 540 mg twice daily. MPA concentrations were measured by high-performance
      liquid chromatography. Twelve-hour pharmacokinetic profiles were obtained after
      the single oral dose and multiple doses on day 4 postoperation. The
      pharmacokinetic parameters were compared between a single dose and multiple
      doses. By using multiple stepwise regression analysis, we obtained two predictive
      equations of MPA systemic exposure. Bland-Altman analysis was developed to test
      agreement between the observed MPA area under the concentration-time curve (AUC)
      and the predicted MPA AUC. RESULTS: The mean (range) MPA AUC was 42 +/- 14.67
      (29.29-75.95) mg/l h after the first dose, and 44.72 +/- 14.57 (32.06-80.79) mg/l
      h on day 4 after operation. MPA exposure provided by a single dose and multiple
      doses were similar (p > 0.05). The best equations obtained were the following:
      20.003 + 1.181C6 h  + 7.22C8 h (r = 0.936) and 17.023 + 3.11C1 h  + 1.245 +
      4.988C8 h (r = 0.964). These equation models showed an optimal agreement between
      the observed MPA AUC and the predicted MPA AUC. CONCLUSIONS: Lower dosing of EC
      MPS, compared with the standard dose (720 mg twice daily), may provide enough MPA
      exposure for Chinese live-donor kidney transplant patients on day 4. Given that
      the MPA exposure by AUC correlates with the incidence of acute rejection episodes
      and transplant vasculopathy, the present findings may have clinical implications,
      and the optimum dose range of EC-MPS for patients in all ranges of body weight
      should also be determined.

PMID- 24673718
TI  - Theoretical investigation of water oxidation processes on small Mn(x)Ti(2-x)O4 (x
      = 0-2) complexes.
AB  - Understanding the water oxidation process on small metal oxide complexes is
      fundamental for developing photocatalysts for solar fuel production. Titanium
      oxide and manganese oxide complexes have high potential as components of a cheap,
      nontoxic, and stable photocatalyst. In this theoretical work, the water oxidation
      process on Mn(x)Ti(2-x)O4 (x = 0-2) clusters is investigated at the BP86 level of
      theory using two water molecules and fully saturated systems. In the oxidation
      cycle using two water molecules, Mn reduces the reaction energy; however, Mn does
      not reduce the reaction energy on the fully saturated system. When two water
      molecules are used, the highest reaction energy in the water oxidation cycle is
      lower than 3 eV, but the highest reaction energy is higher than 3 eV on fully
      saturated systems except for the pure titanium oxide complex which has a highest
      reaction energy of 2.56 eV. Dehydrogenation processes in the water oxidation
      cycle require higher energy than the O-O formation or water adsorption processes.
      The overall dehydrogenation energy is usually smaller on complexes including at
      least one Mn atom and it is smallest on the Mn2O4 complex that has two water
      molecules. Considering the highest reaction energy in the overall water oxidation
      cycle, water oxidation at the manganese atom of MnTiO4 hydrated with two water
      molecules is the most favorable in energy.

PMID- 24673719
TI  - Antitumor effect of fibrin glue containing temozolomide against malignant glioma.
AB  - Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces
      autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue
      (FG) as a drug delivery system for the local administration of high-concentration
      TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography
      studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug
      release potential. We prepared a subcutaneous tumor model by injecting groups of
      mice with three malignant glioma cell lines and examined the antitumor effect of
      TMZ-FG. We estimated the tumor volume and performed immunostaining and
      immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG
      sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth
      was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the
      tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS
      or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in
      subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain,
      we placed it directly on the brain of living mice and stained tissue sections
      obtained in the acute and chronic phase immunohistochemically. In both phases,
      TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe
      new drug delivery system with sustained drug release potential to treat malignant
      glioma. 

PMID- 24673721
TI  - Altered frontal EEG asymmetry in obsessive-compulsive disorder.
AB  - Hemispheric topography of alpha band power in the electroencephalogram has been
      linked to approach/avoidance motivation and may index the risk for anxiety
      disorders and depression. We quantified lower alpha band power (8-10 Hz) in 20
      patients with obsessive-compulsive disorder (OCD) and 20 matched healthy controls
      during blocks of rest and presentation of neutral, aversive, and OCD-related
      pictures. Compared to the control group, OCD patients showed altered asymmetry,
      with frontal alpha power in the 8-10 Hz band being more dominant in the left
      hemisphere across all conditions. This alteration was not observed over parietal
      areas, and also did not show in the upper alpha, and the theta and beta bands.
      This change in hemispheric topography of lower alpha band power supports the
      hypothesis of relatively increased avoidance motivation in OCD. Altered asymmetry
      appears to be traitlike in OCD, suggesting a link to depressive disorders. 

PMID- 24673720
TI  - Specific polyclonal F(ab')2 neutralize a large panel of highly pathogenic avian
      influenza A viruses (H5N1) and control infection in mice.
AB  - AIM: There is still no specific therapy for infection with the highly pathogenic
      avian influenza A virus (HPAI) H5N1, which caused 39 human cases with a 64%
      fatality rate in 2013. MATERIALS & METHODS: We prepared highly purified specific
      equine polyclonal immunoglobulin fragments (F(ab')2) against H5N1 and tested them
      for efficacy in vitro and with different administration schedules in H5N1
      challenged BALB/c mice. RESULTS: in vitro, F(ab')2 neutralized 21 different H5N1
      strains from different areas, representative of 11 different clades and sub
      clades and 9 years of evolution of the virus. In vivo mouse experiments
      identified that the most efficient administration protocol consists of five
      consecutive daily injections after infection; 10 mg/kg giving a 60% increase in
      survival. CONCLUSION: These data demonstrate the ability of anti-H5N1 F(ab')2 to
      markedly reduce the mortality and morbidity associated with infection of mice
      with HPAI H5N1 virus, and their potential for human therapy.

PMID- 24673722
TI  - Endothelial ephrin-B2 is essential for arterial vasodilation in mice.
AB  - OBJECTIVE: The cell surface protein ephrin-B2 is expressed in arterial and not
      venous ECs throughout development and adulthood. Endothelial ephrin-B2 is
      required for vascular development and angiogenesis, but its role in established
      arteries is currently unknown. We investigated the physiological role of ephrin
      B2 signaling in adult endothelium. METHODS: We generated adult conditional
      knockout mice lacking the Efnb2 gene specifically in ECs and evaluated the
      vasodilation responses to blood flow increase and ACh in the cremaster muscle
      preparation by intravital microscope and in carotid artery by in vivo ultrasound.
      RESULTS: We found that the Efnb2 conditional knockout mice were defective in
      acute arterial dilation. Vasodilation was impaired in cremaster arterioles in
      response to either increased flow or ACh, and in the carotid arteries in response
      to increased flow. Levels of cGMP, an effector of NO, were diminished in mutant
      arteries following ACh stimulation. GSNO, a donor for the vasodilator NO,
      alleviated the vasodilatory defects in the mutants. Immunostaining showed that a
      subset of ephrin-B2 proteins colocalized with caveolin-1, a negative regulator of
      eNOS. CONCLUSIONS: Our data suggest that endothelial ephrin-B2 is required for
      endothelial-dependent arterial dilation and NO signaling in adult endothelium.

PMID- 24673723
TI  - Gene expression divergence between malaria vector sibling species Anopheles
      gambiae and An. coluzzii from rural and urban Yaounde Cameroon.
AB  - Divergent selection based on aquatic larval ecology is a likely factor in the
      recent isolation of two broadly sympatric and morphologically identical African
      mosquito species, the malaria vectors Anopheles gambiae and An. coluzzii.
      Population-based genome scans have revealed numerous candidate regions of recent
      positive selection, but have provided few clues as to the genetic mechanisms
      underlying behavioural and physiological divergence between the two species,
      phenotypes which themselves remain obscure. To uncover possible genetic
      mechanisms, we compared global transcriptional profiles of natural and
      experimental populations using gene-based microarrays. Larvae were sampled as
      second and fourth instars from natural populations in and around the city of
      Yaounde, capital of Cameroon, where the two species segregate along a gradient of
      urbanization. Functional enrichment analysis of differentially expressed genes
      revealed that An. coluzzii--the species that breeds in more stable, biotically
      complex and potentially polluted urban water bodies--overexpresses genes
      implicated in detoxification and immunity relative to An. gambiae, which breeds
      in more ephemeral and relatively depauperate pools and puddles in suburbs and
      rural areas. Moreover, our data suggest that such overexpression by An. coluzzii
      is not a transient result of induction by xenobiotics in the larval habitat, but
      an inherent and presumably adaptive response to repeatedly encountered
      environmental stressors. Finally, we find no significant overlap between the
      differentially expressed loci and previously identified genomic regions of recent
      positive selection, suggesting that transcriptome divergence is regulated by
      trans-acting factors rather than cis-acting elements.

PMID- 24673724
TI  - Listeria phage A511, a model for the contractile tail machineries of SPO1-related
      bacteriophages.
AB  - Recognition of the bacterial host and attachment to its surface are two critical
      steps in phage infection. Here we report the identification of Gp108 as the host
      receptor-binding protein of the broad host-range, virulent Listeria phage A511.
      The ligands for Gp108 were found to be N-acetylglucosamine and rhamnose
      substituents of the wall teichoic acids of the bacterial cell wall. Transmission
      electron microscopy and immunogold-labelling allowed us to create a model of the
      A511 baseplate in which Gp108 forms emanating short tail fibres. Data obtained
      for related phages, such as Staphylococcus phages ISP and Twort, demonstrate the
      evolutionary conservation of baseplate components and receptor-binding proteins
      within the Spounavirinae subfamily, and contractile tail machineries in general.
      Our data reveal key elements in the infection process of large phages infecting
      Gram-positive bacteria and generate insights into the complex adsorption process
      of phage A511 to its bacterial host. 

PMID- 24673725
TI  - The determination of histopathological and biochemical effects of the rabbit knee
      joint injected dexketoprofen trometamol.
AB  - This study was conducted to investigate possible histopathological effects and
      biochemical reflections of intra-articular dexketoprofen trometamol. A total of
      24 New Zealand rabbits were included in the study. Blood sampling was carried out
      from all animals on the first day, then they were randomly allocated either to
      the control group (Group C, n = 9) or the dexketoprofen trometamol group (Group
      D, n = 15). Group C underwent each two intra-articular injections of saline, 0.25
      mL into right and 0.50 mL into left knee. Group D was injected 0.25 mL (6.25 mg)
      dexketoprofen trometamol into the right knee and 0.50 mL (12.5 mg) into the left.
      The groups were divided randomly into three. Tissue and blood samples were
      collected from Groups C1 and D1 on the first day, C2 and D2 on the second day and
      C3 and D3 on the 10th day of the study. Interleukin-1 (IL-1beta), interleukin-6
      (IL-6), tumour necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP)
      levels were studied. The histopathological examination of C and D groups did not
      present any deterioration. IL-6 basal levels were significantly higher in Group
      D2 compared with C2 and C3 compared with D3. Basal TNF-alpha levels were higher
      compared with day 1 in Group C1, and IL-6 and CRP levels were higher in Group D3.
      Also, none of the increases in these values are supported by histopathological
      evaluation results. Consequently, we suppose that dexketoprofen trometamol does
      not cause histopathological deterioration in articular cartilage of rabbits, and
      the increases in biochemical parameters exclusively are not clinically
      significant. 

PMID- 24673726
TI  - Ketoacidosis and adrenocortical insufficiency.
AB  - We herein report an autopsy case involving a 27-year-old Caucasian woman
      suffering from chronic adrenocortical insufficiency with a background of a
      polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased
      aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from
      femoral blood as well as decreased cortisol and 17-hydroxycorticosteroid in
      urine. Decreased vitreous sodium and increased 3-beta-hydroxybutyrate and C
      reactive protein concentrations were observed. The cause of death was determined
      to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to
      have precipitated the Addisonian crisis. Traumatic causes of death and third
      party involvement were excluded. The case highlights the importance of
      systematically performing exhaustive postmortem biochemical investigations to
      formulate appropriate hypothesis regarding the pathophysiological mechanisms
      involved in the death process. 

PMID- 24673728
TI  - Boceprevir in liver transplant recipients.
AB  - BACKGROUND: There has been increasing interest in using protease inhibitors with
      pegylated interferon and ribavirin to treat recurrent hepatitis C (HCV) disease
      in liver transplant recipients. METHODS: We retrospectively evaluated the safety
      and efficacy in liver transplant recipients treated for recurrent hepatitis C
      genotype 1 with the combination of peginterferon, ribavirin and boceprevir.
      RESULTS: Twenty liver transplant recipients were treated for recurrent hepatitis
      C. Baseline alanine aminotransferase, total bilirubin and HCV RNA values (+/- SD)
      were 67.5 (+/-50.9) mg/dl, 1.78 (+/-1.99) U/L, and 16 955 510 (+/-21 620 675)
      IU/ml. Anaemia was a common adverse event requiring epoetin in 16 of 20
      recipients and ribavirin dose reductions in 17 of 20 recipients. One-third of
      recipients required a blood transfusion. Filgrastim was used in 11 of 20 patients
      (55%) and eltrombopag in two of 20 recipients (10%) over the course of treatment.
      Serum creatinine level increased significantly from a baseline value of 1.33
      mg/dl to 1.59 mg/dl at week 20 of boceprevir (P < 0.005). The overall sustained
      viral response (SVR) was 50%. Of the 14 patients who had a viral load less than
      1000 IU/ml at week 4 of boceprevir, the SVR was 71%. The SVR was 83% of the 11
      patients who had undetectable viral levels at week 4 of boceprevir. CONCLUSIONS:
      Antiviral therapy utilizing boceprevir in liver transplant recipients requires
      close monitoring. Anaemia and neutropenia were common requiring growth factors in
      most recipients. On-treatment viral responses appear promising but long-term data
      are needed.

PMID- 24673727
TI  - A phase II study of dose-dense and dose-intense ABVD (ABVDDD-DI ) without
      consolidation radiotherapy in patients with advanced Hodgkin lymphoma.
AB  - We explored activity and safety of a dose-dense/dose-intense adriamycin,
      bleomycin, vinblastine and dacarbazine regimen (ABVDDD-DI ) in 82 patients with
      advanced Hodgkin Lymphoma. Patients entered a two-stage Bryant-Day Phase II study
      to receive six cycles of ABVDDD-DI without consolidation radiotherapy. Cycles
      were supported with granulocyte colony-stimulating factor and delivered every 21
      d; drugs were administered on days 1 and 11 at the same doses of standard ABVD
      except for doxorubicin (35 mg/m2; first four cycles only). Co-primary endpoints
      were complete response (CR) rate and severe acute cardiopulmonary toxicity;
      secondary endpoints were event-free (EFS) and disease-free survival (DFS). All
      patients received the four doxorubicin-intensified courses and 96% concluded all
      six cycles (82.3% within the intended 18 weeks). This translated into a 66.9%
      increase of received dose-intensity for doxorubicin and 31.8% for the other
      agents over standard ABVD. The CR rate was 95.1% (78/82) and 87.8% (72/82)
      achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded
      grade 2 and affected 14.6% of patients. Most frequent toxicities were grade 4
      neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2
      mucocutaneous changes (30%). Five-year EFS and DFS was 88.3% and 93.7%,
      respectively. ABVDDD-DI regimen was well-tolerated and ensured substantial CR and
      EFS rates without radiotherapy.

PMID- 24673729
TI  - Variable efficacy of a vaccine and direct-fed microbial for controlling
      Escherichia coli O157:H7 in feces and on hides of feedlot cattle.
AB  - To evaluate the efficacy of a type-III secreted proteins vaccine and a
      Lactobacillus-acidophilus-based direct-fed microbial (DFM) for controlling
      Escherichia coli O157:H7, cattle (n=864) were allocated to the following groups:
      DFM, finishing diets containing 10(9) colony-forming units (CFU)/animal/day L.
      acidophilus and Propionibacterium freudenreichii; VAC, finishing diets and 2 mL
      intramuscular injection of vaccine at allocation and 28 days later; or CON,
      finishing diets only. Cattle within replicates were stratified by initial levels
      of E. coli O157:H7 and randomized to experimental groups, with 30 pens allocated
      on June 15, 2011 (AS1), 18 pens allocated on June 28, 2011 (AS2), and 18 cattle
      per pen. Rectal fecal samples and perineal swabs were collected at 28-day
      intervals until shipment to slaughter (103-145 days on trial). Numbers of cattle
      with enumerable E. coli O157:H7 (>=1.6 CFU/g feces) were reduced in AS1 and AS2
      by VAC (p=0.008), although interventions had no impact on numbers of E. coli
      O157:H7 shed. For AS1, VAC reduced prevalence of E. coli O157:H7 in feces
      (p=0.03) and perineal swabs (p=0.04) in the feeding period but not at shipment to
      slaughter. For AS2, prevalence of E. coli O157:H7 was not reduced in either feces
      or perineal swabs by VAC at any time. For AS1, DFM reduced prevalence of E. coli
      O157:H7 in perineal swabs (p=0.01) during the feeding period. For AS2, DFM
      increased E. coli O157:H7 detection in feces (p=0.03) and perineal swabs (p=0.01)
      at shipment to slaughter. Seventy-five percent of AS1 E. coli O157:H7 isolates
      had only stx1, while 87% of AS2 isolates had stx1 and stx2 genes. Of the two
      interventions, VAC shows the most potential for pre-harvest control of E. coli
      O157:H7, but due to variable efficacy of both DFM and VAC, additional product
      development is necessary to ensure more consistent pre-harvest control of E. coli
      O157:H7.

PMID- 24673730
TI  - The effect of amygdala kindling on neuronal firing patterns in the lateral
      thalamus in the GAERS model of absence epilepsy.
AB  - OBJECTIVE: The co-occurrence of absence and mesial temporal lobe epilepsy is rare
      in both humans and animal models. Consistent with this, rat models of absence
      epilepsy, including genetic absence epilepsy rats from Strasbourg (GAERS), are
      resistant to experimental temporal lobe epileptogenesis, in particular by
      amygdala kindling. Structures within the cortical-thalamocortical system are
      critically involved in the generation and maintenance of the electrographic spike
      and-wave discharges (SWDs) that characterize absence seizures. Using in vivo
      electrophysiologic recordings, this study investigated the role of
      thalamocortical circuitry in the generalization of amygdala-kindling induced
      seizures in the GAERS and the nonepileptic control (NEC) strain of Wistar rats.
      METHODS: GAERS and NEC rats were implanted with a stimulating electrode in
      amygdala and stimulated at afterdischarge threshold twice daily to a maximum
      number of 30 stimulations. Thereafter extracellular single neuron recordings were
      performed in vivo under neuroleptanesthesia in the thalamocortical network.
      RESULTS: In NEC rats, amygdala kindling induced convulsive class V seizures and
      altered characteristics of neuronal activity in the thalamic reticular nucleus
      (TRN), in particular decreased firing rates and increased burst firing patterns.
      Less marked changes were seen in other regions examined: the ventroposteromedial
      nucleus of thalamus (VPM), the CA3 region of the hippocampus, and the deep layers
      (V/VI) of the cortex. GAERS did not progress beyond class II seizures, with a
      matched number of kindling stimulations, and the thalamic neuronal firing
      alterations observed in NEC rats were not seen. SIGNIFICANCE: These data suggest
      that the TRN plays an important role in kindling resistance in GAERS and is
      central to the control of secondary generalization of limbic seizures.

PMID- 24673731
TI  - Prostate tumour volumes: evaluation of the agreement between magnetic resonance
      imaging and histology using novel co-registration software.
AB  - OBJECTIVE: To evaluate the agreement between prostate tumour volume determined
      using multiparametric magnetic resonance imaging (MRI) and that determined by
      histological assessment, using detailed software-assisted co-registration.
      MATERIALS AND METHODS: A total of 37 patients who underwent 3T multiparametric
      MRI (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent
      diffusion coefficient [ADC], dynamic contrast-enhanced [DCE] imaging) were
      included. A radiologist traced the borders of suspicious lesions on T2WI and ADC
      and assigned a suspicion score of between 2 and 5, while a uropathologist traced
      the borders of tumours on histopathological photographs. Software was used to co
      register MRI and three-dimensional digital reconstructions of radical
      prostatectomy specimens and to compute imaging and histopathological volumes.
      Agreement in volumes between MRI and histology was assessed using Bland-Altman
      plots and stratified by tumour characteristics. RESULTS: Among 50 tumours, the
      mean differences (95% limits of agreement) in MRI relative to histology were -32%
      (-128 to +65%) on T2WI and -47% (-143 to +49%) on ADC. For all tumour subsets,
      volume underestimation was more marked on ADC maps (mean difference ranging from 
      57 to -16%) than on T2WI (mean difference ranging from -45 to +2%). The 95%
      limits of agreement were wide for all comparisons, with the lower 95% limit
      ranging between -77 and -143% across assessments. Volume underestimation was more
      marked for tumours with a Gleason score >=7 or a MRI suspicion score 4 or 5.
      CONCLUSION: Volume estimates of prostate cancer using MRI tended to substantially
      underestimate histopathological volumes, with a wide variability in extent of
      underestimation across cases. These findings have implications for efforts to use
      MRI to guide risk assessment.

PMID- 24673732
TI  - The allergic emergency--management of severe allergic reactions.
AB  - Anaphylaxis is characterized by the sudden onset of acute allergic symptoms
      involving two or more organ systems. An acute allergic emergency is a challenge
      for physicians due to its life-threatening potential. The incidence of
      anaphylactic reactions has increased in recent years. Most frequent elicitors of
      mast cell and primarily histamine dependent anaphylactic reactions are food,
      insect venom or drugs. Allergic -reactions are graded into four groups according
      to the classification by Ring and Messmer; grade I is defined by the onset of
      cutaneous symptoms only whereas grade IV is characterized by cardiovascular shock
      as well as cardiac and/or respiratory arrest. The treatment of allergic reactions
      should be guided by the severity of the reaction. Initially an intramuscular
      epinephrine injection into the lateral thigh should be given if cutaneous,
      mucosal and cardiovascular/respiratory symptoms occur. Additionally, the patient
      should receive intravenous antihistamines and corticosteroids. For self-treatment
      in the case of an allergic emergency, oral antihistamines and corticosteroids
      should be prescribed to the patient. 

PMID- 24673733
TI  - High-throughput transcriptome sequencing and preliminary functional analysis in
      four Neotropical tree species.
AB  - BACKGROUND: The Amazonian rainforest is predicted to suffer from ongoing
      environmental changes. Despite the need to evaluate the impact of such changes on
      tree genetic diversity, we almost entirely lack genomic resources. RESULTS: In
      this study, we analysed the transcriptome of four tropical tree species (Carapa
      guianensis, Eperua falcata, Symphonia globulifera and Virola michelii) with
      contrasting ecological features, belonging to four widespread botanical families
      (respectively Meliaceae, Fabaceae, Clusiaceae and Myristicaceae). We sequenced
      cDNA libraries from three organs (leaves, stems, and roots) using 454
      pyrosequencing. We have developed an R and bioperl-based bioinformatic procedure
      for de novo assembly, gene functional annotation and marker discovery. Mismatch
      identification takes into account single-base quality values as well as the
      likelihood of false variants as a function of contig depth and number of
      sequenced chromosomes. Between 17103 (for Symphonia globulifera) and 23390 (for
      Eperua falcata) contigs were assembled. Organs varied in the numbers of unigenes
      they apparently express, with higher number in roots. Patterns of gene expression
      were similar across species, with metabolism of aromatic compounds standing out
      as an overrepresented gene function. Transcripts corresponding to several gene
      functions were found to be over- or underrepresented in each organ. We identified
      between 4434 (for Symphonia globulifera) and 9076 (for Virola surinamensis) well
      supported mismatches. The resulting overall mismatch density was comprised
      between 0.89 (S. globulifera) and 1.05 (V. surinamensis) mismatches/100 bp in
      variation-containing contigs. CONCLUSION: The relative representation of gene
      functions in the four transcriptomes suggests that secondary metabolism may be
      particularly important in tropical trees. The differential representation of
      transcripts among tissues suggests differential gene expression, which opens the
      way to functional studies in these non-model, ecologically important species. We
      found substantial amounts of mismatches in the four species. These newly
      identified putative variants are a first step towards acquiring much needed
      genomic resources for tropical tree species.

PMID- 24673734
TI  - The role of nitric oxide in the cardiovascular response to chronic and acute
      hypoxia in White Leghorn chicken (Gallus domesticus).
AB  - AIM: Prenatal hypoxia due to placental insufficiency results in deleterious
      phenotypes and compensatory mechanisms including increased sympathetic tone.
      Utilizing the embryonic chicken model, we investigated (i) changes in nitric
      oxide (NO)-mediated tone in response to chronic hypoxic development and (ii) the
      in vivo role of NO-mediated tone during acute hypoxic exposure, which has not
      been previously studied. We hypothesized that NO tone on the cardiovascular
      system would be unaffected by chronic hypoxic incubation in White Leghorn chicken
      (Gallus domesticus) embryos. METHODS: We measured arterial pressure, heart rate
      and femoral blood flow (via a Doppler flow probe) in response to acute hypoxia
      (10% O2 ) and pharmacological manipulations in normoxic- and hypoxic (15% O2 )
      incubated embryos. This was performed at 70 and 90% of total incubation time (21
      days). At 70% of incubation (day 15), blood volume and chorioallantoic membrane
      development are maximal; 90% of incubation (day 19) is 1 day prior to lung
      ventilation. RESULTS: Acute hypoxic exposure decreased femoral flow in both 90%
      groups, but increased femoral artery resistance in the hypoxic group. NO tone
      increased during development, but was not affected by hypoxic incubation.
      Inhibition of NO production by L-NAME (100 mg kg(-1) ) revealed that NO plays a
      significant role in the flow response to hypoxia. CONCLUSION: Chronic hypoxic
      incubation has no effect on cardiovascular NO tone during White Leghorn chicken
      development. In the intact animal, NO function during acute hypoxic stress is
      suppressed by hypoxic incubation, indicating that chronic hypoxic stress dampens
      the NO contribution.

PMID- 24673735
TI  - Preparing for tomorrow: molecular diagnostics and the changing nonsmall cell lung
      cancer landscape.
AB  - Over the last 10 to 15 years, the landscape of lung cancer has changed
      dramatically. Where cancers were previously described rather simplistically
      according to histological subtype, now molecular understanding of tumors has
      particularly resulted in segmentation of nonsmall cell lung cancer into many
      different subtypes. A multidisciplinary approach integrating a molecular testing
      algorithm that ideally includes reflex testing at diagnosis is recommended. This
      offers clinicians the opportunity to target treatment according to subtype.
      Identifying patients with rearrangements, such as those associated with the
      echinoderm microtubule-associated protein-like 4 (EML-4) anaplastic lymphoma
      kinase (ALK) fusion gene (the major focus of this paper) has allowed clinicians
      to tailor therapy to target these mutations. The challenge that faces clinicians
      treating lung cancer is how best to implement the science that sits behind these
      targeted therapies in clinical practice through the identification of appropriate
      patients. Precision medicine can lead to the choice of the right medicine for the
      right patients and is proving to be a better approach than treating unselected
      patients with systemic chemotherapy. 

PMID- 24673736
TI  - National Working Group Meeting on ALK diagnostics in lung cancer.
AB  - The global landscape of molecular testing is rapidly changing, with the recent
      publication of the International Association for the Study of Lung Cancer
      (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The
      IASLC/CAP guidelines recommend that tumors from patients with non-small cell lung
      cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth
      factor receptor (EGFR) mutations. The spur for this recommendation is the
      availability of novel therapies that target these rearrangements. This article is
      based on coverage of a Pfizer-sponsored National Working Group Meeting on ALK
      Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in
      Sydney on October 31, 2013. It is based on the presentations given by the authors
      at the meeting and the discussion that ensued. The content for this article was
      discussed and agreed on by the authors. 

PMID- 24673737
TI  - Comparative evaluation of the shaping ability of WaveOne, Reciproc and OneShape
      single-file systems in severely curved root canals of extracted teeth.
AB  - AIM: To compare the shaping ability of WaveOne, Reciproc and OneShape single-file
      systems in severely curved root canals in extracted human molar teeth.
      METHODOLOGY: Sixty mandibular molars with mesio-buccal canals with curvatures
      ranging between 25 degrees  and 35 degrees  and radii of curvature ranging
      between 4 and 9 mm were divided into three groups of 20 teeth each: group W
      (WaveOne), group R (Reciproc) and group O (OneShape). Using standardized pre- and
      post-instrumentation radiographs, straightening of canal curvatures was
      determined using the NIH Image J software. A double-digital standardized
      radiographic technique was used to determine apical transportation at 0.5 mm from
      the working length (1.5 mm coronal to the major foramen). Preparation time and
      instrument failures were also recorded. Data were analysed using one-way analysis
      of variance (anova) and post-hoc Tukey-test. RESULTS: During root canal
      preparation, no instruments fractured but all OneShape instruments were deformed
      after preparation of four canals. The use of OneShape resulted in significantly
      greater canal straightening and apical transportation than WaveOne and Reciproc
      (P < 0.05), with no significant differences between WaveOne and Reciproc (P >
      0.05). Instrumentation with OneShape was significantly faster than with WaveOne
      and Reciproc (P < 0.05), whilst Reciproc was significantly faster than WaveOne (P
      < 0.05). CONCLUSIONS: All instruments were safe to use. Reciproc and WaveOne
      instruments respected the original canal curvature better than OneShape files.
      The use of OneShape instruments required less time to prepare the curved canals
      compared with Reciproc and WaveOne.

PMID- 24673738
TI  - Effects of Lactobacillus casei supplementation on disease activity and
      inflammatory cytokines in rheumatoid arthritis patients: a randomized double
      blind clinical trial.
AB  - AIM: The present study aimed at investigating the effects of Lactobacillus casei
      01 supplementation on symptoms and inflammatory biomarkers of rheumatoid
      arthritis (RA) in women. METHOD: In this randomized double-blind clinical trial,
      female patients with established RA for more than 1 year, 20-80 years of age and
      body mass index (BMI) lower than 40, who followed stable medication for 3 months
      prior to the supplementation, were randomly allocated to receive either one
      capsule containing 10(8) colony forming units (CFU) of L. casei 01, or a placebo
      for 8 weeks; allocation was stratified by BMI and menopausal status. Disease
      activity score-28 (DAS28) was calculated, European League Against Rheumatism
      (EULAR) response was evaluated and the cytokines, interleukin (IL)-1beta, IL-6,
      IL-10, IL-12 and tumor necrosis factor (TNF)-alpha were measured. RESULTS: Thirty
      patients were recruited in each group; 22 and 24 patients were analyzed in the
      probiotic and placebo groups, respectively. L. casei 01 supplementation decreased
      serum high-sensitivity C-reactive protein (hs-CRP) levels, tender and swollen
      joint counts, global health (GH) score and DAS28 (P < 0.05). More patients in the
      L. casei 01 group had moderate response to the treatment, based on the EULAR
      criteria, at the end of the study (P < 0.01). At the end of the study, a
      significant difference was observed between the two groups for IL-10, IL-12 and
      TNF-alpha changes through the study course (P < 0.05), in favor of the probiotic
      group. No adverse effects were reported for the intervention. CONCLUSION:
      Probiotic supplementation may be an appropriate adjunct therapy for RA patients
      and help alleviate symptoms and improve inflammatory cytokines.

PMID- 24673739
TI  - Potent fluorinated agelastatin analogues for chronic lymphocytic leukemia:
      design, synthesis, and pharmacokinetic studies.
AB  - Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in
      Western societies and is currently incurable. Multiple treatment options are
      practiced, but the available small molecule drugs suffer from dose-limiting
      toxicity and undesirable side effects. The need for new, less toxic treatments is
      a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole
      imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro
      activity against primary cell lines of CLL and disclose the synthesis of several
      analogues that are equipotent or exceed the potency of the natural product. The
      novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j),
      showed higher activity than the natural product when tested against the same cell
      lines and is the most potent agelastatin derivative reported to date. A detailed
      in vitro structure-activity relationship of 1a in CLL compared to that of 22
      synthetic analogues is described along with preliminary in vivo pharmacokinetic
      and metabolism studies on the most potent compounds. 

PMID- 24673740
TI  - A retrospective analysis of survival and prognostic factors of male breast cancer
      from a single center.
AB  - BACKGROUND: Less than 1% of all breast cancer cases are found in men, who
      reportedly have inferior outcomes compared with matched women patients. Ethnic
      differences may also affect their prognosis. Here, we investigated overall
      survival (OS) and major prognostic factors for male breast cancer (MBC) in a
      cohort of Egyptian patients. METHODS: We retrospectively analyzed OS in a cohort
      of 69 male patients with MBC who were surgically treated at the Mansoura Cancer
      Center, Egypt between 2000 and 2007. We registered demographic data, age, height,
      weight and body mass index, tumor size, histology, number of infiltrated axillary
      lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM
      staging. Patients' OS was the primary endpoint. Patients received treatment to
      the medical standards at the time of their diagnosis. RESULTS: In the 69 patients
      who met the inclusion criteria and had complete stored patient data, tumors
      ranged from T1c to T3. We could gather cancer-related survival data from only 56
      patients. The collective 5-year survival in this cohort was 46.4%. Only five
      patients had distant metastasis at diagnosis, but they showed a null percent 5
      year survival, whereas those with no lymph node infiltration showed a 100% 5-year
      survival. Lymph node status and tumor grading were the only prognostic factors
      that significantly affected OS. CONCLUSIONS: Lymph node status and tumor grade
      are the most important prognostic factors for overall survival of MBC in Egyptian
      male patients; whereas even remarkably low HR expression in MBC did not
      significantly affect OS. Further research is needed to understand the factors
      that affect this disease.

PMID- 24673741
TI  - Predator-prey trophic relationships in response to organic management practices.
AB  - A broad range of environmental conditions likely regulate predator-prey
      population dynamics and impact the structure of these communities. Central to
      understanding the interplay between predator and prey populations and their
      importance is characterizing the corresponding trophic interactions. Here, we use
      a well-documented molecular approach to examine the structure of the community of
      natural enemies preying upon the squash bug, Anasa tristis, a herbivorous
      cucurbit pest that severely hinders organic squash and pumpkin production in the
      United States. Primer pairs were designed to examine the effects of organic
      management practices on the strength of these trophic connections and link this
      metric to measures of the arthropod predator complex density and diversity within
      an experimental open-field context. Replicated plots of butternut squash were
      randomly assigned to three treatments and were sampled throughout a growing
      season. Row-cover treatments had significant negative effects on squash bug and
      predator communities. In total, 640 predators were tested for squash bug
      molecular gut-content, of which 11% were found to have preyed on squash bugs, but
      predation varied over the season between predator groups (coccinellids,
      geocorids, nabids, web-building spiders and hunting spiders). Through the linking
      of molecular gut-content analysis to changes in diversity and abundance, these
      data delineate the complexity of interaction pathways on a pest that limits the
      profitability of organic squash production.

PMID- 24673743
TI  - Modelling genetic evaluation for dressage in Pura Raza Espanol horses with focus
      on the rider effect.
AB  - The most popular use of the Pura Raza Espanol horse in sport is for dressage
      competitions. Tests on young sport horses were first established in 2004 in Spain
      to collect data for the genetic evaluation of this breed's suitability for
      dressage. The aim of this study was to compare eight different models to find out
      the most appropriate way to include the rider in the genetic evaluation of
      dressage. A progressive removal of systematic effects from model was also
      analysed. A total of 8867 performance records collected between 2004 and 2011
      from 1234 horses aged between 4 and 6 years old were used. The final score in the
      dressage test was used as the performance trait. The pedigree matrix contained
      8487 individuals. A BLUP animal model was applied using a Bayesian approach with
      TM software. The horse's age, gender, travelling time, training level, stud of
      birth and event were included as systematic effects in all the models. Apart from
      the animal and residual effects that were present in all models, different models
      were compared combining random effects such as the rider, match (i.e. rider-horse
      interaction) and permanent environmental effects. A cross-validation approach was
      used to evaluate the models' prediction ability. The best model included the
      permanent environmental, rider and match random effects. As far as systematic
      effects are concerned, the event or the stud of birth was essential effects
      needed to fit the data.

PMID- 24673744
TI  - Multidentate polyethylene glycol modified gold nanorods for in vivo near-infrared
      photothermal cancer therapy.
AB  - Gold nanorods (AuNRs), because of their strong absorption of near-infrared (NIR)
      light, are very suitable for in vivo photothermal therapy of cancer. However,
      appropriate surface modification must be performed on AuNRs before their in vivo
      application because of the high toxicity of their original stabilizer
      cetyltrimethylammonium bromide. Multidentate ligands have attracted a lot of
      attention for modification of inorganic nanoparticles (NPs) because of their high
      ligand affinity and multifunctionality, while the therapeutic effect of
      multidentate ligands modified NPs in vivo remains unexplored. Here, we modified
      AuNRs with a polythiol PEG-based copolymer. The multidentate PEG coated AuNRs
      (AuNR-PTPEGm950) showed good stabilities in high saline condition and wide pH
      range. And they had much stronger resistance to ligand competition of
      dithiothreitol (DTT) than AuNRs coated by monothiol-anchored PEG. The AuNR
      PTPEGm950 had very low cytotoxicity and showed high efficacy for the ablation of
      cancer cells in vitro. Moreover, the AuNR-PTPEGm950 showed good stability in
      serum, and they had a long circulation time in blood that led to a high
      accumulation in tumors after intravenous injection. In vivo photothermal therapy
      showed that tumors were completely cured without reoccurrence by one-time
      irradiation of NIR laser after a single injection of these multidentate PEG
      modified AuNRs. 

PMID- 24673742
TI  - LIM protein JUB promotes epithelial-mesenchymal transition in colorectal cancer.
AB  - Metastasis is the leading cause of cancer-related death in almost all types of
      cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep,
      dynamic biological event, and epithelial-mesenchymal transition (EMT) is a
      critical process during the cascade. Ajuba family proteins are LIM domain
      containing proteins and are reported to be transcription repressors regulating
      different kinds of physiological processes. However, the expression and
      pathological roles of Ajuba family proteins in tumors, especial in tumor
      metastasis, remain poorly studied. Here, we found that JUB, but not the other
      Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell
      lines. Ectopic expression of JUB induced EMT and enhanced motility and
      invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces
      EMT via Snail and JUB is also required for Snail-induced EMT. The expression of
      JUB shows an inverse correlation with E-cadherin expression in clinical
      specimens. Taken together, these findings revealed that the LIM protein JUB
      serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of
      metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of
      metastatic CRC. 

PMID- 24673745
TI  - Athletes confessions: the sports biography as an interaction ritual.
AB  - Commercialization of emotions is not a new phenomenon but in Denmark there is a
      new general trend to tell and sell personal stories in the media. Personal
      deprivation and crises are also major topics in sports media. This paper focuses
      on sports biographies as a book genre that is reviving in popularity. The paper
      approaches the topic through the biographies of one Danish athlete: the former
      professional cyclist, Jesper Skibby, who writes about his doping disclosure and
      shares his personal dilemmas as a former elite sportsman. The thematic text
      analysis orientates around social interactions, emotions, and personality
      constructions. Inspired by microsociology with a Durkheimian flavor of Goffman
      and Hochschild, themes including "face work," "interaction rituals," and
      "emotions management" are discussed. The analysis claims that sharing personal
      information in the media is not only a means of confession and reclaiming status
      but is also business and management - on an intimate level. Telling the story of
      the corrosion of a sporting character has become a hot issue, an entertainment,
      and not least a commercial commitment. 

PMID- 24673746
TI  - Disruption of mutated BRAF signaling modulates thyroid cancer phenotype.
AB  - BACKGROUND: Thyroid cancer is the most common endocrine-related cancer in the
      United States and its incidence is rising rapidly. Since among various genetic
      lesions identified in thyroid cancer, the BRAFV600E mutation is found in 50% of
      papillary thyroid cancers and 25% of anaplastic thyroid cancers, this mutation
      provides an opportunity for targeted drug therapy. Our laboratory evaluated
      cellular phenotypic effects in response to treatment with PLX4032, a BRAFV600E
      specific inhibitor, in normal BRAF-wild-type thyroid cells and in BRAFV600E
      positive papillary thyroid cancer cells. METHODS: Normal BRAF-wild-type thyroid
      cells and BRAFV600E-mutated papillary thyroid cancer cells were subjected to
      proliferation assays and analyzed for cell death by immunofluorescence. Cell
      cycle status was determined using an EdU uptake assay followed by laser scanning
      cytometry. In addition, expression of proteins within the MAPK signal
      transduction pathway was analyzed by Western blot. RESULTS: PLX4032 has potent
      anti-proliferative effects selectively in BRAF-mutated thyroid cancer cells.
      These effects appear to be mediated by the drug's activity of inhibiting
      phosphorylation of signaling molecules downstream of BRAF within the pro-survival
      MAPK pathway. Interestingly, PLX4032 promotes the phosphorylation of these
      signaling molecules in BRAF-wild-type thyroid cells. CONCLUSIONS: These findings
      support further evaluation of combinational therapy that includes BRAFV600E
      inhibitors in thyroid cancer patients harboring the BRAFV600E mutation.

PMID- 24673747
TI  - Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine
      imbalance, inflammation and hypoxia in women from north-west Colombia.
AB  - BACKGROUND: A large-scale study was set up in order to study the epidemiology,
      clinical aspects, and immunopathology of gestational and placental malaria in
      north-west Colombia. In this region, recent reports using a qPCR technique,
      confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax,
      up to 45%. Given the high rates of infection observed both in mother and
      placenta, a first exploratory study was proposed in order to characterize the
      effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp.
      infected placentas. METHODS: A descriptive, prospective, cross-sectional design
      was applied to pregnant women with (PM+) and without (PM-) placental malaria.
      Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines
      IL-2, IL-4, IL-10, IFN-gamma and TNF, were measured in peripheral and placental
      blood using a quantitative PCR. The percentage of apoptotic cells was determined
      with a TUNEL assay. RESULTS: In total 50 placentas were studied: 25 were positive
      for submicroscopic infection and 25 were negative for Plasmodium infection.
      Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while
      IL-2 was high in peripheral blood of the same group. Expression of TNF and
      IFNgamma in peripheral blood of the PM + group was high. Similarly, the apoptotic
      index and Fas expression were significantly high in PM+. However, FasL expression
      was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and
      hypoxia markers (COX-1, COX-2) were high in the PM + group. CONCLUSION: During
      placental malaria expression of some pro-inflammatory cytokines is up-regulated
      and markers of hypoxia and tissue damage are increased in cases of submicroscopic
      infection.

PMID- 24673748
TI  - Experiences and treatment patterns of hypogonadal men in a U.S. health system.
AB  - OBJECTIVE: To examine self-reported experiences with hypogonadism (HG) and
      patterns of testosterone replacement therapy (TRT) in men seeking care in a U.S.
      healthcare system. METHODS: Men >= 18 years old with HG were identified from the
      2008-2010 Reliant electronic medical records database. Surveys, including
      validated instruments for measuring symptoms of HG, were collected and evaluated
      for demographic and behavioural data. RESULTS: Surveys were mailed to 133 men
      with HG in 2012. Of the 107 surveys returned, 95 were included in the final
      analysis. Most respondents were Caucasian (90.5%). Men reported developing
      symptoms of HG, as well as being diagnosed, at a median age of 50 years. The most
      common symptoms reported as reasons for seeking treatment were erectile
      dysfunction (66.3%), fatigue (59.0%) and decreased sex drive (57.9%). These
      continued to be the most bothersome symptoms at the time of the survey regardless
      of whether the patient received treatment, although men who were currently taking
      TRT reported less severe symptoms. Approximately 88% of men reported taking TRT
      at some point, with 61.9% on therapy at the time of the survey. CONCLUSIONS: This
      study examined men's experiences with HG, including symptoms, quality of life,
      and treatments. Some symptoms continued despite treatment, and therapy was
      discontinued at a high rate, which men generally attributed to cost and
      perceptions of efficacy. In light of this lack of adherence, patients may benefit
      from appropriate expectation setting regarding reasonable timelines for symptom
      improvement, the strengths and challenges of various TRT formulations, the
      importance of adherence and the benefits and risks of TRT.

PMID- 24673749
TI  - Association between computed tissue density asymmetry in bilateral mammograms and
      near-term breast cancer risk.
AB  - This study investigated association between bilateral mammographic density
      asymmetry and near-term breast cancer risk. A data base of digital mammograms
      acquired from 690 women was retrospectively collected. All images were originally
      interpreted as negative by radiologists. During the next subsequent screening
      examinations (between 12 and 36 months later), 230 women were diagnosed positive
      for cancer, 230 were recalled for additional diagnostic workups and proved to be
      benign, and 230 remained negative (not recalled). We applied a computerized
      scheme to compute the differences of five image features between the left and
      right mammograms, and trained an artificial neural network (ANN) to compute a
      bilateral mammographic density asymmetry score. Odds ratios (ORs) were used to
      assess associations between the ANN-generated scores and risk of women having
      detectable cancers during the next screening examinations. A logistic regression
      method was applied to test for trend as a function of the increase in ANN
      generated scores. The results were also compared with ORs computed using other
      existing cancer risk factors. The ORs showed an increasing risk trend with the
      increase in ANN-generated scores (from 1.00 to 9.07 between positive and negative
      case groups). The regression analysis also showed a significant increase trend in
      slope (p < 0.05). No significant increase trends of the ORs were found when using
      woman's age, subjectively rated breast density, or family history of breast
      cancer. This study demonstrated that the computed bilateral mammographic density
      asymmetry had potential to be used as a new risk factor to improve discriminatory
      power in predicting near-term risk of women developing breast cancer. 

PMID- 24673750
TI  - Perioperative and renal functional outcomes of elective robot-assisted partial
      nephrectomy (RAPN) for renal tumours with high surgical complexity.
AB  - OBJECTIVE: To evaluate the perioperative, postoperative and functional outcomes
      of robot-assisted partial nephrectomy (RAPN) for renal tumours with high surgical
      complexity at a large volume centre. PATIENTS AND METHODS: Perioperative and
      functional outcomes of RAPNs for renal tumours with a Preoperative Aspects and
      Dimensions Used for an Anatomical (PADUA) score of >=10 performed at our
      institution between September 2006 and December 2012 were collected in a
      prospectively maintained database and analysed. Surgical complications were
      graded according to the Clavien-Dindo classification. Serum creatinine and
      estimated glomerular filtration rate (eGFR) were assessed at the third
      postoperative day and 3-6 months after RAPN. RESULTS: In all, 44 RAPNs for renal
      tumours with PADUA scores of >=10 were included in the analysis; 23 tumours
      (52.3%) were cT1b. The median (interquartile range; range) operative time,
      estimated blood loss and warm ischaemia time (WIT) were 120 (94, 132; 60-230)
      min, 150 (80, 200; 25-1200) mL and 16 (13.8, 18; 5-35) min, respectively. Two
      intraoperative complications occurred (4.5%): one inferior vena caval injury and
      one bleed from the renal bed, which were both managed robotically. There were
      postoperative complications in 10 patients (22.7%), of whom four (9.1%) were high
      Clavien grade, including two bleeds that required percutaneous embolisation, one
      urinoma that resolved with ureteric stenting and one bowel occlusion managed with
      laparoscopic adhesiolysis. Two patients (4.5%) had positive surgical margins
      (PSMs) and were followed expectantly with no radiological recurrence at a mean
      follow-up of 23 months. The mean serum creatinine levels were significantly
      increased after surgery (121.1 vs 89.3 MUmol/L; P = 0.001), but decreased over
      time, with no significant differences from the preoperative values at the 6-month
      follow-up (96.4 vs 89.3 MUmol/L; P = 0.09). The same trend was seen for eGFR.
      CONCLUSION: In experienced hands RAPN for renal tumours with a PADUA score of
      >=10 is feasible with short WIT, acceptable major complication rate and good long
      term renal functional outcomes. A slightly higher risk of PSMs can be expected
      due to the high surgical complexity of these lesions. The robotic technology
      allows a safe expansion of the indications of minimally invasive PN to
      anatomically very challenging renal lesions in referral centres.

PMID- 24673751
TI  - Metals and electrolytes in sclerotic hippocampi in patients with drug-resistant
      mesial temporal lobe epilepsy.
AB  - An altered metal and electrolyte profile has been implicated in the pathologic
      mechanisms of chronic epilepsy; however, no study has comprehensively measured
      hippocampal concentrations of these elements in patients with mesial temporal
      lobe epilepsy and hippocampal sclerosis (mTLE-HS). We therefore analyzed
      hippocampi of 24 patients with drug-resistant mTLE-HS (mean age 35.6 +/- 9.4
      years) who underwent anterior temporal lobe resection and amygdalohippocampectomy
      and 17 hippocampi obtained by autopsy from 13 controls (mean age 40.5 +/- 12.9
      years), using inductively coupled plasma optical emission spectrometry (ICP-OES).
      Epileptic hippocampi showed significantly lower concentrations (MUg/g of tissue)
      of copper (HS: 2.34 +/- 0.12; control [C]: 3.57 +/- 0.33; p < 0.001), manganese
      (HS: 0.205 +/- 0.030; C: 0.409 +/- 0.064; p = 0.004), and potassium (HS: 2,001 +/
      59; C: 2,322 +/- 61; p < 0.001), and increased sodium levels (HS: 1,131 +/- 22;
      C: 1,040 +/- 25; p = 0.010). Zinc, iron, calcium, and magnesium levels did not
      differ in HS and controls. In summary, copper and manganese levels are deficient,
      whereas iron level is unchanged in hippocampi from patients with mTLE-HS. Our
      results provide a basis for understanding the potential involvement of different
      metals and electrolytes in the pathology of HS.

PMID- 24673752
TI  - Sexual dimorphism in finger ridge breadth measurements: a tool for sex estimation
      from fingerprints.
AB  - Previous research has demonstrated significant sexual dimorphism in friction
      ridge skin characteristics. This study uses a novel method for measuring sexual
      dimorphism in finger ridge breadths to evaluate its utility as a sex estimation
      method from an unknown fingerprint. Beginning and ending in a valley, the width
      of ten parallel ridges with no obstructions or minutia was measured in a sample
      of 250 males and females (N = 500). The results demonstrate statistically
      significant differences in ridge breadth between males and females (p < 0.001),
      with classification accuracy for each digit varying from 83.2% to 89.3%.
      Classification accuracy for the pooled finger samples was 83.9% for the right
      hand and 86.2% for the left hand, which is applicable for cases where the digit
      number cannot be determined. Weight, stature, and to a lesser degree body mass
      index also significantly correlate with ridge breadth and account for the degree
      of overlap between males and females. 

PMID- 24673753
TI  - A general protein O-glycosylation system within the Burkholderia cepacia complex
      is involved in motility and virulence.
AB  - Bacteria of the Burkholderia cepacia complex (Bcc) are pathogens of humans,
      plants, and animals. Burkholderia cenocepacia is one of the most common Bcc
      species infecting cystic fibrosis (CF) patients and its carriage is associated
      with poor prognosis. In this study, we characterized a general O-linked protein
      glycosylation system in B. cenocepacia K56-2. The PglLBc O
      oligosaccharyltransferase (O-OTase), encoded by the cloned gene bcal0960, was
      shown to be capable of transferring a heptasaccharide from the Campylobacter
      jejuni N-glycosylation system to a Neisseria meningitides-derived acceptor
      protein in an Escherichia coli background, indicating that the enzyme has relaxed
      specificities for both the sugar donor and protein acceptor. In B cenocepacia K56
      2, PglLBc is responsible for the glycosylation of 23 proteins involved in diverse
      cellular processes. Mass spectrometry analysis revealed that these proteins are
      modified with a trisaccharide HexNAc-HexNAc-Hex, which is unrelated to the O
      antigen biosynthetic process. The glycosylation sites that were identified
      existed within regions of low complexity, rich in serine, alanine, and proline.
      Disruption of bcal0960 abolished glycosylation and resulted in reduced swimming
      motility and attenuated virulence towards both plant and insect model organisms.
      This study demonstrates the first example of post-translational modification in
      Bcc with implications for pathogenesis. 

PMID- 24673755
TI  - Neuro-ophthalmologic manifestations of systemic lupus erythematosus: a systematic
      review.
AB  - Herein we summarize the clinical presentation, treatment and outcome of neuro
      ophthalmologic manifestations in patients with systemic lupus erythematosus
      (SLE). We performed a systematic review of the neuro-ophthalmologic
      manifestations of SLE reported in the English literature from 1970 to 2010 by a
      Medline search. The prevalence of neuro-ophthalmologic manifestations is 3.6% in
      adult and 1.6% in childhood SLE patients. Neuro-ophthalmologic manifestations of
      SLE are highly variable, with the commonest presentation being optic neuritis,
      followed by myasthenia gravis, visual field defects and pseudotumor cerebri. The
      underlying pathology was thought to be either SLE activity or its vascular
      complications. Most neuro-ophthalmologic manifestations of SLE are responsive to
      high-dose glucocorticoids. Anticoagulation is indicated when there is concomitant
      antiphospholipid syndrome. SLE-related neuromyelitis optica is often refractory
      to treatment and 92% of patients require multiple immunosuppressive protocols.
      Neuro-ophthalmologic manifestations of SLE are uncommon but heterogeneous. The
      prognosis of neuro-ophthalmologic manifestations in SLE is generally good because
      of their rapid response to glucocorticoids. Relapses of these manifestations may
      be reduced by the use of maintenance immunosuppression. Cyclophosphamide,
      azathioprine, plasmapheresis, intravenous immunoglobulin and rituximab can be
      considered in glucocorticoid-dependent or refractory cases. Anticoagulation is
      indicated when there is concomitant antiphospholipid syndrome. 

PMID- 24673754
TI  - Ganglioside deficiency causes inflammation and neurodegeneration via the
      activation of complement system in the spinal cord.
AB  - BACKGROUND: Gangliosides, sialic acid-containing glycosphingolipids, are highly
      expressed in nervous systems of vertebrates and have been considered to be
      involved in the development, differentiation, and function of nervous tissues.
      Recent studies with gene-engineered animals have revealed that they play roles in
      the maintenance and repair of nervous tissues. In particular, knockout (KO) mice
      of various ganglioside synthase genes have exhibited progressive
      neurodegeneration with aging. However, neurological disorders and pathological
      changes in the spinal cord of these KO mice have not been reported to date.
      Therefore, we examined neurodegeneration in double knockout (DKO) mice of
      ganglioside GM2/GD2 synthase (B4GANLT1) and GD3 synthase (ST8SIA1) genes to
      clarify roles of gangliosides in the spinal cord. METHODS: Motor neuron function
      was examined by gait analysis, and sensory function was analyzed by von Frey
      test. Pathological changes were analyzed by staining tissue sections with Kluver
      Barrera staining and by immunohistochemistry with F4/80 and glial fibrillary
      acidic protein (GFAP). Gene expression profiles were examined by using DNA micro
      array of RNAs from the spinal cord of mice. Triple knockout mice were generated
      by mating DKO and complement component 3 (C3)-KO mice. Gene expression of the
      complement system and cytokines was examined by reverse transcription-polymerase
      chain reaction (RT-PCR) as a function of age. RESULTS: DKO mice showed
      progressive deterioration with aging. Correspondingly, they exhibited shrunk
      spinal cord, reduced thickness of spinal lamina II and III, and reduced neuronal
      numbers in spinal lamina IX, spinal lamina II, and spinal lamina I. Complement
      related genes were upregulated in DKO spinal cord. Moreover, complement
      activation and inflammatory reactions were detected by GFAP-active astrocyte,
      microglial accumulation, and increased inflammatory cytokines such as tumor
      necrosis factor-alpha (TNFalpha) and interleukin-1-beta (IL-1beta). Triple
      knockout mice showed restoration of reduced neuron numbers in the spinal cord of
      DKO mice, getting close to levels of wild-type mice. CONCLUSIONS: Disruption in
      the architecture of lipid rafts in the spinal cord was not so prominent,
      suggesting that mechanisms distinct from those reported might be involved in the
      complement activation in the spinal cord of DKO mice. Gene profiling revealed
      that inflammation and neurodegeneration in the spinal cord of DKO mice are, at
      least partly, dependent on complement activation.

PMID- 24673756
TI  - Validation of the emotion thermometers and hospital anxiety and depression scales
      in Singapore: Screening cancer patients for distress, anxiety and depression.
AB  - AIM: To validate the emotion thermometer (ET) and hospital anxiety and depression
      scales (HADS) in Singapore, screening cancer patients for distress, anxiety and
      depression. METHODS: Three hundred fifteen cancer patients from National Cancer
      Centre and Singapore General Hospital participated in the study. Interviews and
      assessments were conducted in English, assessing patients' sociodemographic data
      and screening for emotional symptoms using the ET, HADS and Mini-International
      Neuropsychiatric Interview (MINI) tools. RESULTS: Fifty-three patients (16.83%)
      fulfilled the MINI criteria for major depressive disorder and 30 patients
      (12.77%) for generalized anxiety disorder. The ET depression thermometer
      correlated positively with HADS depression subscale, r = 0.645 (P < 0.01), with
      area under curve (AUC) value being 0.76, when cutoff score is 3. The ET anxiety
      thermometer correlated positively with HADS anxiety subscale, r = 0.632 (P <
      0.01), with an AUC value of 0.76, when cutoff score is 4. The ET distress
      thermometer correlated positively with HADS depression subscale, r = 0.506 (P <
      0.01), with AUC value being 0.72, when cutoff score is 2, the ET distress
      thermometer also correlated positively with HADS anxiety subscale, r = 0.652 (P <
      0.01), with the AUC value being 0.77, when cutoff score is 4. Using MINI
      diagnoses for anxiety and depression as the gold standard, cutoff score for HADS
      depression scale is 7, which yielded an AUC of 0.826. The cutoff score for HADS
      anxiety scale is 5, yielding an AUC of 0.779. CONCLUSION: Results from the study
      support the use of both ET and HADS as valid and reliable instruments assessing
      for distress, anxiety and depression in cancer patients.

PMID- 24673757
TI  - Unravelling the nature of Waiparaconus, a pennatulacean (Cnidaria: Octocorallia)
      from the Late Mesozoic-Early Cainozoic of the Southern Hemisphere.
AB  - Enigmatic calcareous conical fossils have been known from marine Paleocene-Eocene
      sequences of New Zealand since the early 1870s. More recently, similar fossils
      have been recorded from both Late Cretaceous marine sequences of Western
      Australia, New Caledonia and Antarctica, and possibly from the Eocene of South
      America. The present paper extends the record to the late Cretaceous of New
      Caledonia. These remains are unlike any living taxa, and have been variously
      interpreted as molluscs (rudistid bivalves), cirripedes (stalked barnacles),
      annelids and inorganic structures. Assignation to the Cirripedia has been refuted
      by Buckeridge (1983, 1993), who proposed that the material would be better placed
      within the Cnidaria. We investigate this hypothesis in light of the New
      Caledonian material and by comparison with living gorgonians and pennatulaceans,
      and demonstrate that Waiparaconus is best placed within the Pennatulacea.
      Waiparaconus zelandicus varies in form somewhat, with 3 morphotypes defined and
      reinforced by geography. Comment is provided on the imperative to fit organic
      remains into known groups, with reflection on what may happen if taxa are left in
      insertae sedis. 

PMID- 24673758
TI  - Early-Middle Ordovician brachiopod dispersal patterns in South China.
AB  - Paleobiogeographic patterns of the brachiopod faunas before and during the first
      radiation of the Great Ordovician Biodiversification Event (GOBE) in South China
      at 6 different localities from the upper Jiangnan Slope to the vast area of the
      Upper Yangtze Platform show several interesting features. First, the initial
      brachiopod diversity acme was accompanied by both high origination and extinction
      rates. Second, no significant changes took place in the taxonomic composition and
      paleobiogeographic pattern of the brachiopod fauna during the radiation at 5 of
      the 6 localities studied except the near shore locality, where the first
      brachiopod radiation was much later than at other localities and was marked by a
      dramatic increase in endemic constituents. Third, orthides were the predominant
      brachiopod group during the radiation, and regional brachiopod taxa played a
      significant role in defining the paleobiogeographic pattern of the radiation.
      Fourth, the first brachiopod radiation was associated with 3 major pulses of
      onshore migration from the upper Jiangnan Slope through the central Upper Yangtze
      Platform to the near shore settings of the platform, with the middle pulse being
      the most significant. Finally, paleogeographic dispersal took place in both
      onshore and offshore directions, although the onshore expansion was more
      prominent; several key brachiopods, such as Paralenorthis, Nocturnellia,
      Protoskenidioides, Nereidella, Euorthisina and Yangtzeella, first appeared on the
      upper Jiangnan Slope and later formed distinct, and taxonomically diverse,
      communities on the Upper Yangtze Platform. The paleogeographic dispersal of
      brachiopods is considered to be closely related to the tectonic evolution of the
      Qianzhong Arch. 

PMID- 24673759
TI  - A giant crocodile in the Dubois Collection from the Pleistocene of Kali Gedeh
      (Java).
AB  - The fauna of the Pleistocene Homo-bearing sites of Java has been well known for
      more than a century. A recent revision of the crocodylian remains confirmed both
      the validity of Gavialis bengawanicus and the synonymization of Crocodylus
      ossifragus with C. siamensis. Here we report on a still unpublished crocodylian
      specimen collected by Eugene Dubois in the latest Early Pleistocene of Kali Gedeh
      that can be tentatively referred to the genus Crocodylus. The size of the
      specimen, the approximately 1 m long lower jaw in particular, indicated that this
      crocodile attained a total length of approximately 6 or 7 m. Along with specimens
      from the Plio-Pleistocene of Africa, this material provides evidence for
      gigantism in Crocodylus. It is not clear whether or not the 'temperature-size
      rule' applies to fossil crocodylians, but due to the growing interest in
      predicting future temperature-related size changes of the extant organisms, it
      would be interesting to study in detail the past reaction to temperature changes
      of crocodylians and other terrestrial ectothermic animals. 

PMID- 24673760
TI  - Phylogenetic relationships of the Australian Oligo-Miocene ratite Emuarius gidju
      Casuariidae.
AB  - In Australia, ratites (Aves: Palaeognathae) are represented in the extant fauna
      by the family Casuariidae with 1 species of emu Dromaius novaehollandiae and 1
      cassowary Casuarius casuarius. The Australian fossil record reveals no other
      extinct ratite families but there are a number of other casuariid species. Most
      significant of these, due to its Oligo-Miocene age and because it is known from
      abundant material, is Emuarius gidju. Here, we describe additional material and
      confirm that the taxon had a temporal range of Late Oligocene to Middle Miocene
      (approximately 24-15 Ma). We reveal new morphological details, including notably
      that the species had relatively much smaller eyes than D. novaehollandiae, in
      addition to a less well-developed cursorial ability, as inferred from its pelvic
      limb. In these respects, Emuarius is similar to Casuarius and suggest that it was
      adapted to denser vegetation than the open woodlands and grasslands that
      characterise much of Australia today and to which D. novaehollandiae, with its
      large eyes and enhanced cursorial ability, is strongly adapted. Emuarius was
      compared to and found to be distinct from the poorly provenanced Australian
      fossil species C. lydekkeri. We conducted a phylogenetic analysis of
      morphological data that robustly shows that E. gidju is the sister taxon of
      Dromaius and together these taxa form a clade that is sister to Casuarius. This
      indicates that the evolution towards enhanced cursorality that characterises
      Dromaius took place after the divergence of the emu-cassowary lineages and was
      likely not the driving mechanism of this divergence. Comparisons between D.
      novaehollandiae and D. baudinianus revealed no qualitative skeletal differences
      and we suggest that the latter taxon is best considered to be an island dwarf
      that should be taxonomically recognized at a subspecific level only. 

PMID- 24673761
TI  - Parallel patterns and trends in functional structures in extinct island mammals.
AB  - Endemic mammalian species on islands are generally known to have followed a
      different evolutionary pathway than their mainland relatives. General patterns,
      such as body size trends, have been described regularly. However, most island
      mammal species are unique and each of them is adapted to a specific local niche
      as part of an equally specific ecological assemblage. Therefore, comparing island
      species across taxa, islands and time is inherently dangerous without
      understanding the adaptational value of the studied feature in the compared taxa
      and without taking the ecological setting of the taxa into account. In this
      contribution, general and recurring patterns are described per taxon. Some
      features, like body mass change and sturdy limbs, are relatively general, whereas
      most features, like bone fusions and change of orbital axis, occur only in a very
      few taxa. Some features are even contradictory, such as brain size and degree of
      hypsodonty, with each taxon having its own particular design. In conclusion,
      general patterns are more often than not just trends and need to be applied with
      caution. 

PMID- 24673762
TI  - Late Miocene/Early Pliocene vertebrate fauna from Mallorca (Balearic Islands,
      Western Mediterranean): an update.
AB  - The vertebrate fossil record from the Balearic Islands (western Mediterranean)
      has improved considerably over the past decade, especially in Mallorca and
      Menorca. In Menorca, the Pliocene terrestrial fauna was updated by the discovery
      and description of the large-sized leporid Nuralagus, several reptiles and an
      amphibian. In Mallorca, paleontological exploration yielded 2 deposits with a
      Late Miocene/Early Pliocene chronology, Calo den Rafelino (CdR) and Na Burguesa-1
      (NB-1). So far, 4 new mammalian taxa and 2 new reptiles have been identified for
      the CdR deposit, whereas the faunal assemblage from the recently discovered
      deposit (Apr 2012) of NB-1 is currently composed of, at least, 6 terrestrial
      mammals, 8 reptiles and an amphibian. Its faunal composition and some primitive
      characteristics of the obtained taxa suggest that the chronology of this deposit
      is slightly earlier than the CdR. The terrestrial vertebrates recorded in these 2
      Mallorcan deposits are changing the view of the paleofaunal assemblage previously
      known for the Plio-Pleistocene of the island. Morphological characteristics
      displayed by some of the taxa suggest that these faunas would be at the beginning
      of an isolated evolution. In this paper we present a preliminary report on the
      fossils recovered from the NB-1 deposit, as well as some unpublished data from
      CdR, and we analyze the whole fauna from both Mallorcan deposits, focusing on
      taxonomical and paleobiogeographical aspects. 

PMID- 24673763
TI  - How large are the extinct giant insular rodents? New body mass estimations from
      teeth and bones.
AB  - The island rule entails a modification of the body size of insular mammals, a
      character related with numerous biological and ecological variables. From the
      Miocene to human colonization (Holocene), Mediterranean and Canary Islands were
      unaltered natural ecosystems, with paleofaunas formed with endemic giant rodents
      among other mammals. Our aim is to create methods to estimate the body masses of
      fossil island rodents and address the nature of ecological pressures driving the
      island rule. We created regression equations based on extant rodent data and used
      these to estimate the body masses of the extinct species. Our results show strong
      correlations between teeth, cranial and postcranial measurements and body mass,
      except for the length of the long bones, the transversal diameter of the distal
      tibia and the anteroposterior diameter of the proximal tibia, where the equations
      were less reliable. The use of equations obtained from a more homogeneous group
      (suborder and family) is preferable when analyzing the area of the first molar.
      The new regressions were applied to estimate the body masses of some
      Mediterranean and Canarian fossil rodents (Canariomys, C. bravoi 1.5 kg and C.
      tamarani 1 kg; Hypnomys, H. morpheus 230 g and H. onicensis 200 g; and
      Muscardinus cyclopeus 100 g). Our results indicate that under absence of
      predation, resource availability (island area) is the key factor that determines
      the size of the Canariomys sp. However, under presence of specialized predators
      (birds of prey), body size evolution is less pronounced (Hypnomys sp.). 

PMID- 24673764
TI  - Lights and shadows in the evolutionary patterns of insular bovids.
AB  - Endemic bovids are intriguing elements of insular faunas. The living species
      include the Japanese serow (Capricornis crispus) and the Formosan serow (C.
      swinhoei), the tamaraw from Mindoro, Philippines, (Bubalus mindorensis) and the
      anoas (B. depressicornis and B. quarlesi), 2 species of dwarf buffalos endemic to
      Sulawesi, Indonesia. Fossil endemic bovids are only recorded in some Asian, North
      American and Western Mediterranean islands. Here we present a comprehensive
      overview of the changes in body size and evolutionary patterns exhibited by both
      extant and extinct insular bovids. Our appraisal indicates that each insular
      representative of Bovidae shows its own peculiar evolutionary model, albeit some
      parallel trends exist (e.g. reduction in body size, allometric changes in limb
      bones, alteration of the life history traits). Some changes in morphology (e.g.
      the simplification of horn cores, the increase in hypsodonty, the acquisition of
      a 'low-gear' locomotion), for instance, appear as common, albeit not general,
      patterns triggered by a combination of selective forces. Body size patterns
      support the 'generality of the island rule' and suggest that biotic interaction
      had/have a major role in influencing body size evolution in these species,
      although in different ways on different islands. All things considered, available
      evidence suggest that a major role in the evolution of insular bovids is played
      by the structure of the insular community, the nature of available niches and by
      the dynamics of ecological interactions. 

PMID- 24673766
TI  - Mechanistic action of gibberellins in legume nodulation.
AB  - Legume plants are capable of entering into a symbiotic relationship with rhizobia
      bacteria. This results in the formation of novel organs on their roots, called
      nodules, in which the bacteria capture atmospheric nitrogen and provide it as
      ammonium to the host plant. Complex molecular and physiological changes are
      involved in the formation and establishment of such nodules. Several
      phytohormones are known to play key roles in this process. Gibberellins
      (gibberellic acids; GAs), a class of phytohormones known to be involved in a wide
      range of biological processes (i.e., cell elongation, germination) are reported
      to be involved in the formation and maturation of legume nodules, highlighted by
      recent transcriptional analyses of early soybean symbiotic steps. Here, we
      summarize what is currently known about GAs in legume nodulation and propose a
      model of GA action during nodule development. Results from a wide range of
      studies, including GA application, mutant phenotyping, and gene expression
      studies, indicate that GAs are required at different stages, with an optimum,
      tightly regulated level being key to achieve successful nodulation. Gibberellic
      acids appear to be required at two distinct stages of nodulation: (i) early
      stages of rhizobia infection and nodule primordium establishment; and (ii) later
      stages of nodule maturation. 

PMID- 24673767
TI  - Characterization of the caleosin gene family in the Triticeae.
AB  - BACKGROUND: The caleosin genes encode proteins with a single conserved EF hand
      calcium-binding domain and comprise small gene families found in a wide range of
      plant species. Some members of the gene family have been shown to be upregulated
      by environmental stresses including low water availability and high salinity.
      Caleosin 3 from wheat has been shown to interact with the alpha-subunit of the
      heterotrimeric G proteins, and to act as a GTPase activating protein (GAP). This
      study characterizes the size and diversity of the gene family in wheat and
      related species and characterizes the differential tissue-specific expression of
      members of the gene family. RESULTS: A total of 34 gene family members that
      belong to eleven paralogous groups of caleosins were identified in the hexaploid
      bread wheat, T. aestivum. Each group was represented by three homeologous copies
      of the gene located on corresponding homeologous chromosomes, except the caleosin
      10, which has four gene copies. Ten gene family members were identified in
      diploid barley, Hordeum vulgare, and in rye, Secale cereale, seven in
      Brachypodium distachyon, and six in rice, Oryza sativa. The analysis of gene
      expression was assayed in triticale and rye by RNA-Seq analysis of 454 sequence
      sets and members of the gene family were found to have diverse patterns of gene
      expression in the different tissues that were sampled in rye and in triticale,
      the hybrid hexaploid species derived from wheat and rye. Expression of the gene
      family in wheat and barley was also previously determined by microarray analysis,
      and changes in expression during development and in response to environmental
      stresses are presented. CONCLUSIONS: The caleosin gene family had a greater
      degree of expansion in the Triticeae than in the other monocot species,
      Brachypodium and rice. The prior implication of one member of the gene family in
      the stress response and heterotrimeric G protein signaling, points to the
      potential importance of the caleosin gene family. The complexity of the family
      and differential expression in various tissues and under conditions of abiotic
      stress suggests the possibility that caleosin family members may play diverse
      roles in signaling and development that warrants further investigation.

PMID- 24673769
TI  - Development of livestock production in the tropics: farm and farmers'
      perspectives.
AB  - Because of an increasing demand for animal-source foods, an increasing desire to
      reduce poverty and an increasing need to reduce the environmental impact of
      livestock production, tropical farming systems with livestock must increase their
      productivity. An important share of the global human and livestock populations
      are found within smallholder mixed-crop-livestock systems, which should,
      therefore, contribute significantly towards this increase in livestock
      production. The present paper argues that increased livestock production in
      smallholder mixed-crop-livestock systems faces many constraints at the level of
      the farm and the value chain. The present paper aims to describe and explain the
      impact of increased production from the farm and farmers' perspective, in order
      to understand the constraints for increased livestock production. A framework is
      presented that links farming systems to livestock value chains. It is concluded
      that farming systems that pass from subsistence to commercial livestock
      production will: (1) shift from rural to urban markets; (2) become part of a
      different value chain (with lower prices, higher demands for product quality and
      increased competition from peri-urban producers and imports); and (3) have to
      face changes in within-farm mechanisms and crop-livestock relationships. A model
      study showed that feed limitation, which is common in tropical farming systems
      with livestock, implies that maximum herd output is achieved with small herd
      sizes, leaving low-quality feeds unutilised. Maximal herd output is not achieved
      at maximal individual animal output. Having more animals than required for
      optimal production - which is often the case as a larger herd size supports non
      production functions of livestock, such as manure production, draught, traction
      and capital storage - goes at the expense of animal-source food output. Improving
      low-quality feeds by treatment allows keeping more animals while maintaining the
      same level of production. Ruminant methane emission per kg of milk produced is
      mainly determined by the level of milk production per cow. Part of the methane
      emissions, however, should be attributed to the non-production functions of
      ruminants. It was concluded that understanding the farm and farmers' perceptions
      of increased production helps with the understanding of productivity increase
      constraints and adds information to that reported in the literature at the level
      of technology, markets and institutions. 

PMID- 24673768
TI  - Feeling well and talking about sex: psycho-social predictors of sexual
      functioning after cancer.
AB  - BACKGROUND: Changes to sexual wellbeing are acknowledged to be a long-term
      negative consequence of cancer and cancer treatment. These changes can have a
      negative effect on psychological well-being, quality of life and couple
      relationships. Whilst previous conclusions are based on univariate analysis,
      multivariate research can facilitate examination of the complex interaction
      between sexual function and psycho-social variables such as psychological
      wellbeing, quality of life, and relationship satisfaction and communication in
      the context of cancer, the aim of the present study. METHOD: Six hundred and
      fifty seven people with cancer (535 women, 122 men) and 148 partners (87 women,
      61 men), across a range of sexual and non-sexual cancers, completed a survey
      consisting of standardized measures of sexual functioning, depression and
      anxiety, quality of life, relationship satisfaction, dyadic sexual communication,
      and self-silencing, as well as ratings of the importance of sex to life and
      relationships. RESULTS: Men and women participants, reported reductions in sexual
      functioning after cancer across cancer type, for both people with cancer and
      partners. Multiple regression analysis examined psycho-social predictors of
      sexual functioning. Physical quality of life was a predictor for men and women
      with cancer, and for male partners. Dyadic sexual communication was a predictor
      for women with cancer, and for men and women partners. Mental quality of life and
      depression were also predictors for women with cancer, and the lower self
      sacrifice subscale of self-silencing a predictor for men with cancer. CONCLUSION:
      These results suggest that information and supportive interventions developed to
      alleviate sexual difficulties and facilitate sexual renegotiation should be
      offered to men and women with both sexual and non-sexual cancers, rather than
      primarily focused on individuals with sexual and reproductive cancers, as is the
      case currently. It is also important to include partners in supportive
      interventions. Interventions aimed at improving sexual functioning should include
      elements aimed at improving physical quality of life and sexual communication,
      with a focus on psychological wellbeing also being important for women with
      cancer.

PMID- 24673770
TI  - Serum carotenoid levels and risk of lung cancer death in US adults.
AB  - Lung cancer is one of the most common cancers worldwide and is the leading cause
      of cancer-induced death in the USA. Although much attention has been focused on
      the anti-carcinogenic effect of consuming carotenoid-containing food or
      supplements, the results have been inconsistent. We investigated whether serum
      carotenoid levels were associated with the mortality risk of lung cancer in US
      adults using data from a nationally representative sample. The data were obtained
      from the Third Nutrition and Health Examination Survey (NHANES III) database and
      the NHANES III Linked Mortality File. A total of 10,382 participants aged over
      20,years with available serum carotenoid levels and no other missing information
      on questionnaires and biomarkers at baseline (NHANES III) were included in the
      present study. Of the 10,382 participants, 161 subjects died due to lung cancer.
      We found that high serum levels of alpha-carotene and beta-cryptoxanthin at
      baseline were significantly associated with a lower risk of lung cancer death.
      When we stratified the risk by current smoking status, the risk of death of
      current smokers was significantly decreased to 46% (95% confidence interval, 31
      94%) for alpha-carotene and 61% (95% confidence interval, 19-80%) for beta
      cryptoxanthin. By contrast, no association was observed among never/former
      smokers at baseline. High serum levels of alpha-carotene and beta-cryptoxanthin
      are associated with a lower risk of lung cancer death in US adults.

PMID- 24673771
TI  - Kidney injury in cirrhosis: pathophysiological and therapeutic aspects of
      hepatorenal syndromes.
AB  - Acute kidney injury (AKI) is frequent in patients with cirrhosis. AKI and
      hyponatraemia are major determinants of the poor prognosis in advanced cirrhosis.
      The hepatorenal syndrome (HRS) denotes a functional and potential reversible
      impairment of renal function. Type 1 HRS, a special type of AKI, is a rapidly
      progressive AKI, whereas the renal function in type 2 HRS decreases more slowly.
      HRS is precipitated by factors such as sepsis that aggravate the effective
      hypovolaemia in decompensated cirrhosis, by lowering arterial pressure and
      cardiac output and enhanced sympathetic nervous activity. Therefore, attempts to
      prevent and treat HRS should seek to improve liver function and to ameliorate
      arterial hypotension, central hypovolaemia and cardiac output, and to reduce
      renal vasoconstriction. Ample treatment of HRS is important to prevent further
      progression and death, but as medical treatment only modestly improves long-term
      survival, these patients should always be considered for liver transplantation.
      Hyponatraemia, defined as serum sodium <130 mmol/L, is common in patients with
      decompensated cirrhosis. From a pathophysiological point of view, hyponatraemia
      is related to an impairment of renal solute-free water excretion most likely
      caused by an increased vasopressin secretion. Patients with cirrhosis mainly
      develop hypervolaemic hyponatraemia. Current evidence does not support routine
      use of vaptans in the management of hyponatraemia in cirrhosis.

PMID- 24673772
TI  - Aspergillus tracheobronchitis in critically ill patients with chronic obstructive
      pulmonary diseases.
AB  - Aspergillus tracheobronchitis (ATB) is considered as an unusual form of invasive
      aspergillosis and has a fatal outcome. There is little current information on
      several aspects of chronic obstructive pulmonary diseases (COPD) complicated by
      ATB, the frequency of which is expected to increase in the coming years. In a
      prospective study of invasive bronchial-pulmonary aspergillosis (IBPA) in a
      critically ill COPD population, three proven cases of ATB were identified. The
      three new cases, combined with eight previously reported cases of COPD with ATB
      over a 30-year period (1983-2013), were analysed. Among 153 critically ill COPD
      patients admitted to the ICU, eight cases were complicated by ATB [23.5% of IBPA
      (8 of 34); and 5.2% of COPD (8 of 153)], and three cases were finally diagnosed
      as proven ATB by histopathological findings. Among the three new cases reported
      and the eight published cases, the overall mortality rate was 72.7% (8 of 11
      cases), with a median of 11.5 days (range, 7-27 days) between admission to death.
      The mortality rate was significantly higher in patients with invasive pulmonary
      aspergillosis (IPA) [100% (8 of 8 patients)] than in patients without parenchyma
      invasion [0% (0 of 3 patient), P = 0.006]. Seven patients (77.8%) received
      systemic corticosteroid therapy and three patients (33.3%) inhaled
      corticosteroids before diagnosis with ATB. Dyspnoea resistant to corticosteroids
      (77.8%) was the most frequent symptom. The radiological manifestations progressed
      rapidly in three patients (75%) who had normal chest X-rays (CXRs) at admission.
      Pseudomembranous lesions were the most frequent form (54.5%) observed by
      bronchoscopy. Aspergillus fumigatus was the most frequently isolated pathogen
      (40%). ATB is an uncommon cause of exacerbation in approximately 5% of critically
      ill COPD patients admitted to the ICU, and may progress rapidly to IPA with a
      high mortality rate. Dyspnoea resistant to corticosteroids and appropriate
      antibiotics with a negative CXR should raise the suspicion of ATB. Early
      diagnosis of ATB is based on bronchoscopic examination and proven diagnosis maybe
      safely established with a bronchial mucous biopsy.

PMID- 24673773
TI  - From circuit activity to network connectivity and back: the case of obsessive
      compulsive disorder.

PMID- 24673774
TI  - Using graph theory to connect the dots in obsessive-compulsive disorder.

PMID- 24673775
TI  - How much improvement is needed for a real difference of lower urinary tract
      symptoms after long-term combination therapy for benign prostatic hyperplasia.
AB  - AIMS: Medical treatment is the first choice in the treatment of lower urinary
      tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). This
      retrospective study investigated the changes of measured parameters after 4-year
      medical therapy based on the reported quality of life index (QoL-I) in the
      International Prostate Symptom Score (IPSS) questionnaire. MATERIALS AND METHODS:
      Patients with symptomatic BPH received 4-year treatment with doxazosin 4 mg and
      dutasteride 0.5 mg daily. All patients had a total prostate volume (TPV) of >= 30
      ml and IPSS >= 8 at baseline. The measured parameters included IPSS, maximum flow
      rate (Qmax), postvoid residual volume (PVR), TPV and prostate specific antigen
      (PSA). The changes of parameters from baseline to 4th year were compared between
      patients with different QoL-I. RESULTS: Among 243 enrolled patients, 161(66.3%)
      completed the treatment, 82(33.7%) did not complete the 4-year treatment because
      of unsatisfactory results (51, 21%) or converted to surgery (31, 12.8%). At the
      4th year, 147/161 (91.3%) patients reported a QoL-I of 0-2. All measured
      parameters show significant improvement. Among the patients with satisfactory QoL
      (QoL-I 0-2), IPSS <= 7 was noted in 113 (76.9%), Qmax >= 15 ml/s in 54 (36.79%),
      PVR < 50 ml in 83 (56.5%), TPV <= 39 ml in 63 (42.9%), and PSA <= 1.5 ng/ml in 66
      (44.9%). Except for the IPSS, a significant change in each parameter from
      baseline to the 4th year was noted in less than 50% of the patients with
      satisfactory QoL. CONCLUSION: Based on the patients' reported QoL-I, a successful
      therapeutic result does not need the improvement of all measured parameters.

PMID- 24673776
TI  - Classical dynamin DNM1 and DNM3 genes attain maximum expression in the normal
      human central nervous system.
AB  - Dynamin is a super-family of large GTPase proteins that polymerise during their
      biological activity. Dynamin polymers form around lipid tubes and contribute to
      the membrane fission and scission of nascent vesicles from parent membranes. Here
      we used the NCBI Gene Expression Omnibus (GEO) database and the BioGPS gene
      expression portal to study differential dynamin gene expression in normal human
      organs or tissues. From the GDS1096 and GDS596 dataset, we downloaded the
      relative expression levels of dynamin-related genes (presented as percentages),
      with respect to all of the other genes on the array (platform Affymetrix GPL96),
      which includes the best characterised human genes. The expression profiles of
      dynamin in the central nervous system (CNS) are clearly distinct from the
      expression profiles in the other organs or tissues studied. We found that the
      classical dynamin DNM1 and DNM3 genes reach their maximum expression levels (100%
      of maximal expression) in all normal human CNS tissues studied. This is in
      contrast to the expression profile in the other normal human organs or tissues
      studied, in which both dynamin DNM1 and DNM3 genes showed approximately 50%
      maximal expression. This data mining analysis supports the concept that there is
      a relationship between the synapse and the molecular function of dynamin,
      suggesting a new field of work in the study of neurodegenerative diseases. 

PMID- 24673777
TI  - Phylogeography of Ramalina menziesii, a widely distributed lichen-forming fungus
      in western North America.
AB  - The complex topography and climate history of western North America offer a
      setting where lineage formation, accumulation and migration have led to elevated
      inter- and intraspecific biodiversity in many taxa. Here, we study Ramalina
      menziesii, an epiphytic lichenized fungus with a range encompassing major
      ecosystems from Baja California to Alaska to explore the predictions of two
      hypotheses: (i) that the widespread distribution of R. menziesii is due to a
      single migration episode from a single lineage and (ii) that the widespread
      distribution is due to the formation and persistence of multiple lineages
      structured throughout the species' range. To obtain evidence for these
      predictions, we first construct a phylogenetic tree and identify multiple
      lineages structured throughout the species' range--some ancient ones that are
      localized and other more recent lineages that are widely distributed. Second, we
      use an isolation with migration model to show that sets of ecoregion populations
      diverged from each other at different times, demonstrating the importance of
      historical and current barriers to gene flow. Third, we estimated migration rates
      among ecoregions and find that Baja California populations are relatively
      isolated, that inland California ecoregion populations do not send out emigrants
      and that migration out of California coastal and Pacific Northwest populations
      into inland California ecoregions is high. Such intraspecific geographical
      patterns of population persistence and dispersal both contribute to the wide
      range of this genetically diverse lichen fungus and provide insight into the
      evolutionary processes that enhance species diversity of the California Floristic
      Province.

PMID- 24673778
TI  - The role of mitochondria in mTOR-regulated longevity.
AB  - Several unbiased genome-wide RNA interference (RNAi) screens have pointed to
      mitochondrial metabolism as the major factor for lifespan regulation. However,
      conflicting data remain to be clarified concerning the mitochondrial free radical
      theory of aging (MFRTA). Recently, mTOR (mechanistic target of rapamycin) has
      been proposed to be the central regulator of aging although how mTOR modulates
      lifespan is poorly understood. Interestingly, mTOR has been shown to regulate
      many aspects of mitochondrial function, such as mitochondrial biogenesis,
      apoptosis, mitophagy and mitochondrial hormesis (mitohormesis) including the
      retrograde response and mitochondrial unfolded protein response (mito-UPR). Here
      we discuss the data linking mitochondrial metabolism to mTOR regulation of
      lifespan, suggesting that hormetic effects may be key to explaining some
      controversial results regarding the MFRTA. We also discuss the possibility that
      dysfunction of mitochondrial adaptive responses rather than free radicals per se
      contributes to the aging process. 

PMID- 24673779
TI  - The horse as teacher: really?

PMID- 24673780
TI  - Disparities in treatment of people with mental disorder in non-psychiatric
      hospitals: a review of the literature.
AB  - People with mental disorder experience a heavy burden of physical ill-health.
      This, alongside structural health-system changes, means more people with mental
      disorder are being cared for in non-psychiatric hospitals. This article reports
      on 32 studies that have investigated the care and outcomes of people with
      comorbid mental and physical health problems in non-psychiatric hospitals.
      Prevalence of mental disorder ranged between 4%-46%, and rates of psychiatric
      referral was 2%-10%. The receipt of invasive cardiac procedures was markedly
      reduced for those with mental disorder. Likelihood of experiencing an adverse
      event, post-operative complication or increased length of stay was also elevated
      for those with mental disorder. 

PMID- 24673781
TI  - What determines whether nurses provide physical health care to consumers with
      serious mental illness?
AB  - People with serious mental illness (SMI) have heightened rates of chronic
      physical disease. This study aimed to identify what nurse and organisational
      factors predict physical health care provided by nurses in contact with consumers
      with SMI, through a survey in Australia (N=643). Statistical analyses revealed
      that physical health care could be accounted for in terms of nurse views on
      consumer health, rights and nurse role ideal ('nurses should be involved in
      physical health care'), and organisational factors. However, organisational
      factors may be more important in determining physical health care than views and
      perceptions about consumers, roles and ideals. 

PMID- 24673782
TI  - Efficacy of psychoeducation and relaxation interventions on stress-related
      variables in people with mental disorders: a literature review.
AB  - This paper aimed to critically review and summarize empirical evidence concerning
      the efficacy of psychoeducation or relaxation-based stress management
      interventions on stress-related variables in people with mental disorders.
      Electronic databases were used during the literature search. Thirteen articles
      that fulfilled the preset eligible criteria were included in the review. Findings
      indicated that psychoeducation and relaxation-based interventions mitigated
      stress and depression; and enhanced relaxation intensity and knowledge on stress
      management. However, mixed results were obtained on anxiety. In addition,
      interventions using virtual reality technology revealed positive effects on
      depression, relaxation intensity and anxiety. Limitations and recommendations for
      future research are discussed. 

PMID- 24673783
TI  - Factors associated with the emotional distress of women family members of adults
      with serious mental illness.
AB  - Women family members of adults with serious mental illness are at great risk for
      emotional distress. This study examined associations between characteristics of
      60 women (age, race, and education), their relatives with mental illness (age,
      diagnosis, and years since diagnosis), and the family situation (relationship,
      living arrangements, and care provided) and symptoms of emotional distress.
      Depressive symptoms were greater among those with younger, non-sibling relatives.
      Anxiety was greater among Caucasians and those with a recently diagnosed family
      member, particularly bipolar disorder. Anger was associated with providing direct
      care. The findings are informative for tailoring interventions to minimize
      emotional distress in future family caregivers. 

PMID- 24673784
TI  - Peripheral brain derived neurotrophic factor (BDNF) in bulimia nervosa: a
      systematic review.
AB  - INTRODUCTION: Currently, there is limited understanding of the etiology of BN.
      While multifaceted etiology is likely, several neurobiological factors may play a
      role. Brain derived neurotrophic factor (BDNF), a potential biomarker linked to
      eating and weight disorders, is one factor of recent investigation. This paper
      examined studies comparing BDNF blood levels in BN to healthy control (HC)
      subjects. METHODS: A systematic review of the literature was conducted utilizing
      five databases (PubMed, CINAHL, EMBASE, PsycINFO, and Medline). Key terms
      included eating disorders, BDNF, and bulimia nervosa. CONCLUSIONS: BDNF blood
      levels appear lower in BN than in HC subjects; however, studies are needed to
      examine the influence of possible correlates including symptom severity, mood,
      medications, exercise, and substance use.

PMID- 24673785
TI  - Perceived social support is a partial mediator of the relationship between
      depressive symptoms and quality of life in patients receiving hemodialysis.
AB  - BACKGROUND: The meaning of social support is well documented, but less is known
      about mediating characteristics that examine which patients with end stage renal
      disease (ESRD) and depressive symptoms are most likely to benefit. AIMS: The aim
      of this study was to examine whether perceived social support mediated depressive
      symptoms on the outcome of quality of life (QoL). DESIGN: A correlational, cross
      sectional study was conducted with a convenience sampling of 190 patients with
      ESRD. RESULTS: There was partial mediation effect of social support on depressive
      symptoms in the prediction of QoL. CONCLUSION: Effective management of depressive
      symptoms will improve QoL mostly when social support is promoted in patients with
      ESRD receiving hemodialysis.

PMID- 24673787
TI  - Development, validation and initial outcomes of a questionnaire to investigate
      the views of nurses working in a mental health setting regarding a
      cardiometabolic health nursing role.
AB  - People with serious mental illness experience disparities in primary health care.
      One solution is a specialist nursing position responsible for the coordination of
      the primary care of people with serious mental illness. However the views of
      nurses regarding this proposed role are only beginning to emerge. This study
      reports the readability, factorability, internal consistency and responses from a
      questionnaire regarding the views of nurses working in a mental health setting
      regarding the proposed role. The questionnaire was determined to have adequate
      readability, and internal consistency. Nurses are positive towards the
      development of the role however the cost-effectiveness should be considered. 

PMID- 24673786
TI  - Prevalence of nurses' smoking habits in psychiatric and general hospitals in
      China.
AB  - This study determined the prevalence of lifetime and current smoking and the
      correlates of current smoking in nurses working in psychiatric and general
      hospitals in China. Of 807 distributed questionnaires, 799 nurses who were
      working in two psychiatric hospitals (n=387, 48.4%), and one general hospital
      (n=412, 51.6%) had analyzable data. Socio-demographic, alcohol use and smoking
      data were collected with a self-reported questionnaire. Work-related stress was
      evaluated with the Nurse Stress Inventory. In the whole sample, the lifetime
      smoking prevalence was 7.6% (females=2.1% vs. males=48.9%, p<0.0001; psychiatric
      nurses=14.5% vs. non-psychiatric nurses=1.2%, p<0.0001). The prevalence of
      current smoking was 7.1% (females=2.1% vs. males=44.7%, p<0.0001; psychiatric
      nurses=13.4% vs. non-psychiatric nurses=1.2%, p<0.0001). In a multiple logistic
      regression analysis, age 30 years or older, male gender, having children, being a
      psychiatric nurse and alcohol consumption were positively associated with
      smoking, while being a nursing officer was negatively associated with smoking
      (r(2) = 0.513, p<0.0001). Considering the harmful effects of smoking as well as
      second-hand smoking in the presence of children, effective measures to promote
      smoking cessation for male, older and psychiatric nurses and those with children
      are warranted. 

PMID- 24673788
TI  - Implications of a longitudinal cognitive intervention program in mild Alzheimer's
      disease.
AB  - The implications of a longitudinal (5 years) intervention program in a mild
      Alzheimer's disease (mAD) patient targeting mainly the language deficits were
      investigated. The program had 2 parts: the intensive one included training
      strategies and tasks that enhanced his impairments (memory, naming,
      comprehension), and the second one (the next 4 years), without guidelines or
      teaching. The first follow up (11 months later) showed significant improvements
      to memory, categorical verbal fluency, comprehension and written narrative
      ability even to untrained functions (behavior and functional ability). The second
      follow up (5 years later) showed retained improvement to delayed memory tasks,
      language and general cognitive state. Long life cognitive programs retrograde the
      mAD and seem to maintain the independence of the patient and make remote the
      possibility of the institutionalization.

PMID- 24673789
TI  - Selection, use and psychometric properties of physical activity measures to
      assess individuals with severe mental illness: a narrative synthesis.
AB  - This research provides a critical consideration of the outcome measures used to
      assess physical activity in individuals with severe mental illness. A narrative
      synthesis was utilised to provide a simple juxtapose of the current research. A
      sensitive topic-based search strategy was conducted in order to identify studies
      that met the eligibility criteria. Fifty two studies met the inclusion criteria
      and 5 were identified specially as validation studies. The current research
      identified several methodological shortcomings. The justification and choice of
      outcome measure used is often weak and only five studies have validated a
      specific outcome measure of physical activity. Within these validation studies,
      the validation process often lacked a consideration of agreement between
      measures. Accelerometers have been most frequently used as a criterion measure,
      notably the RT3 tri-axial accelerometer. Objective based measures may be best
      placed to consider physical activity levels, although, methodological
      considerations for the utilization of such tools is required. Self-report
      questionnaires have benefits for use in this population but require further
      validation. Researchers and clinicians need to carefully consider what outcome
      measure they are using and be aware of the development, scope and purpose of that
      measure. 

PMID- 24673791
TI  - New design of shape memory polymers based on natural rubber crosslinked via oxa
      Michael reaction.
AB  - Shape memory polymers (SMPs) based on natural rubber were fabricated by
      crosslinking epoxidized natural rubber with zinc diacrylate (ZDA) using the oxa
      Michael reaction. These SMPs possessed excellent shape fixity and recovery. The
      glass transition largely accounted for the fixing of the SMPs temporary shape.
      Increasing the ZDA content allowed the trigger temperature (20-46  degrees C) and
      recovery time (14-33 s) of the SMPs to be continuously tuned. Nanosized silica
      (nanosilica) was incorporated into the neat polymers to further increase the
      flexibility and tune the recovery stress. The nanosilica-SMPs exhibited
      exceptionally high strength in a rubbery state (>20 MPa). The nanosilica-SMPs
      exhibited high transparency, making them suitable in visible heat-shrinkable
      tubes. 

PMID- 24673790
TI  - Relationship between parenting and proactive versus reactive aggression among
      Chinese preschool children.
AB  - This study examines the relationship between parenting and proactive versus
      reactive aggression among preschool children in China. Children (1164) from 10
      kindergartens in Shanghai were rated by their parents and teachers using the
      Parent Behavior Inventory (PBI) and the Aggressive Behavior-Teacher's Checklist.
      Children had higher levels of reactive than proactive aggression, and older
      children and boys had higher levels of both proactive and reactive aggression.
      Hostile/coercive parenting style and low father education were significantly
      linked to aggression in children. These findings suggest that parenting style and
      type of aggression should be addressed when considering prevention and
      intervention. 

PMID- 24673792
TI  - Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil
      therapy versus entecavir monotherapy for the treatment-naive patients with
      chronic hepatitis B: a meta-analysis.
AB  - BACKGROUND: Currently, there is no consensus on the efficacy and resistance of de
      novo combination therapy versus monotherapy for treatment naive patients of
      chronic hepatitis B (CHB). OBJECTIVES: The aim of this study was to evaluate the
      effectiveness and resistance of de novo combination of lamivudine (LAM) and
      adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for
      nucleos(t)ide-naive patients with CHB. STUDY DESIGN: Publications on the
      effectiveness and resistance of LAM plus ADV versus ETV monotherapy for
      nucleos(t)ide-naive patients with CHB were identified by a search of PubMed,
      Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological
      Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e
      antigen seroconversion, and viroligic response were extracted and combined to
      obtain an integrated result. Viral resistance and safety were reviewed. RESULTS:
      Five eligible studies (328 patients in total) were included in the analysis. LAM
      plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12
      weeks than that of ETV monotherapy. At 48 weeks, the combination group had
      superior viroligic response rates compared with ETV group (90.0% vs. 78.9%,
      P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates
      was not found. At week 96, LAM + ADV was more effective than ETV in ALT
      normalization [RR = 1. 11, 95% CI (1.02, 1.21), P =0.01] and HBeAg seroconversion
      [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was
      found in the virologic response (P =0.23). No viral resistance occurred in
      combination therapy and six patients in ETV group were experienced with viral
      breakthrough. Both groups were well tolerated. CONCLUSION: The de novo LAM plus
      ADV combination therapy for treatment-naive patients with CHB was greater than
      ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to
      96 weeks. The rate of emergence of viral resistance in the combination group was
      less than that in the ETV monotherapy.

PMID- 24673793
TI  - Effects of supplementing n-3 fatty acid enriched eggs and walnuts on
      cardiovascular disease risk markers in healthy free-living lacto-ovo-vegetarians:
      a randomized, crossover, free-living intervention study.
AB  - BACKGROUND: Plant and marine n-3 fatty acids (FA) may favorably modify select
      markers of cardiovascular disease risk. Whether supplementing the habitual diet
      of lacto-ovo-vegetarians (LOV) with walnuts (containing alpha-linolenic acid,
      ALA) and n-3 FA enriched eggs (containing primarily docosahexaenoic acid, DHA and
      ALA) would have equivalent effects on CVD risk factors is explored in this study.
      METHODS: In this study, 20 healthy free-living LOVs following their habitual diet
      were randomly assigned in a crossover design to receive one of three supplements:
      n-3 FA enriched egg (6/week), walnuts (28.4 g, 6/week) or a standard egg, 6/week
      (control) for 8 weeks each with 4-wk washout between treatments. Erythrocyte
      membrane fatty acids, serum lipids and inflammatory markers were measured at the
      end of each treatment. RESULTS: Dietary compliance was observed by an expected
      increase in erythrocyte membrane ALA following the walnut treatment and in DHA
      following the n-3 FA enriched egg treatment. Walnut treatment lowered serum
      triacylglycerol, total cholesterol and Apo B (p < 0.05) compared to the standard
      egg but not the n-3 FA enriched egg treatment. However, walnut treatment
      significantly reduced total: HDL cholesterol ratio compared to both egg
      treatments. There were no differences between treatments for any of the
      inflammatory markers. CONCLUSIONS: For LOV, a direct source of DHA such as n-3 FA
      enriched eggs seems necessary to increase membrane levels of DHA. However for
      producing an overall favorable blood lipid profile, daily consumption of a
      handful of walnuts rich in ALA may be a preferred option for lacto-ovo
      vegetarian.

PMID- 24673794
TI  - Comparing female-based contraceptive methods in patients with systemic lupus
      erythematosus, rheumatoid arthritis and a healthy population.
AB  - AIM: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is
      10 times more prevalent in women, particularly those of reproductive age. The
      varying effects of pregnancy on SLE and the differences between available SLE
      treatments make pregnancy timing and contraceptive methods significant. We aimed
      to determine the contraceptive methods used by SLE patients in the north-west
      part of Turkey, and compared them with those used by rheumatoid arthritis (RA)
      patients and healthy controls. METHOD: The study was comprised of 113 SLE
      patients, and 84 RA patients at the Rheumatology Outpatient Clinic of Uludag
      University Medical Faculty. RESULTS: Twenty-three (20.3%) out of 113 SLE
      patients, 18 (21.4%) out of 84 RA patients and 17 (18.6%) out of 92 healthy
      controls did not use any contraceptive methods. Use of the withdrawal and condom
      methods was more common among SLE patients, accounting for 61% (withdrawal 32.7%,
      condom 28.3%). Moreover, 52% of SLE and 50% of RA patients were neither given
      information about contraceptive methods nor offered a suggested method, compared
      to 34% in the health control group. CONCLUSIONS: The prevalence of oral
      contraceptive use is low in Turkey; notwithstanding the withdrawal and condom
      methods, which are frequently used despite their high failure risk. Although
      pregnancy timing is of great importance for SLE patients, necessary information
      and recommendations concerning contraceptive methods have been ignored and the
      use of effective methods is not a priority.

PMID- 24673795
TI  - Identification and characterization of the 'missing' terminal enzyme for siroheme
      biosynthesis in alpha-proteobacteria.
AB  - It has recently been shown that the biosynthetic route for both the d1 -haem
      cofactor of dissimilatory cd1 nitrite reductases and haem, via the novel
      alternative-haem-synthesis pathway, involves siroheme as an intermediate, which
      was previously thought to occur only as a cofactor in assimilatory
      sulphite/nitrite reductases. In many denitrifiers (which require d1 -haem), the
      pathway to make siroheme remained to be identified. Here we identify and
      characterize a sirohydrochlorin-ferrochelatase from Paracoccus pantotrophus that
      catalyses the last step of siroheme synthesis. It is encoded by a gene annotated
      as cbiX that was previously assumed to be encoding a cobaltochelatase, acting on
      sirohydrochlorin. Expressing this chelatase from a plasmid restored the wild-type
      phenotype of an Escherichia coli mutant-strain lacking sirohydrochlorin
      ferrochelatase activity, showing that this chelatase can act in the in vivo
      siroheme synthesis. A DeltacbiX mutant in P. denitrificans was unable to respire
      anaerobically on nitrate, proving the role of siroheme as a precursor to another
      cofactor. We report the 1.9 A crystal structure of this ferrochelatase. In vivo
      analysis of single amino acid variants of this chelatase suggests that two
      histidines, His127 and His187, are essential for siroheme synthesis. This CbiX
      can generally be identified in alpha-proteobacteria as the terminal enzyme of
      siroheme biosynthesis. 

PMID- 24673796
TI  - Idiopathic granulomatous mastitis--a prospective study of 49 women and treatment
      outcomes with steroid therapy.
AB  - Idiopathic granulomatous mastitis (IGM) is an infrequently reported benign breast
      disease of unknown etiology. Surgical treatment has been widely advocated but can
      be disfiguring. We describe demographic and clinico-pathologic features of women
      with IGM in a safety net hospital, and evaluate steroid therapy as a breast
      conserving modality of treatment. We also examine a possible ethnic predominance
      in Hispanic women. We conducted an observational prospective cohort study of all
      women with biopsy-proven granulomatous mastitis in the breast clinics of an urban
      safety net public hospital from 2006 to 2010. Demographic, ethnic and clinical
      data, treatment history, and response to treatment were collected. Patients were
      followed up prospectively to determine the type of treatment prescribed, complete
      resolution of disease, and median time to resolution. A nested case-control study
      was conducted to examine Hispanic prevalence using chi-square statistic. The mean
      age was 35 years. 80% were Hispanic. 80% presented with a painful breast mass.
      59% initially received antibiotics with incomplete resolution. 90% women were
      prescribed oral steroids, 3% underwent surgical treatment, and 6% remained under
      observation with spontaneous resolution. Of those who received steroid, 80% had
      complete resolution of disease with a median time to complete resolution of 159
      days (IQR 120-241 days). Ethnicity data in a nested case-control study revealed
      that women in the IGM group were more likely to be Hispanic than in the control
      group with an odds ratio of 3 (95% CI 1.42-6.24, p-value 0.0032). IGM is a benign
      but locally aggressive breast disease. Treatment with steroids is an effective
      breast-conserving option. Predominance in Hispanic women of childbearing age
      suggests a common genetic, environmental, immunologic, or infectious etiology and
      warrants further study with a multi-disciplinary approach. 

PMID- 24673798
TI  - Mammography performance in Oman: Review of factors influencing cancer yield and
      positive predictive value.
AB  - AIM: The aim of this study is to assess mammography performance in Oman by
      estimating the breast cancer rate and the positive predictive value (PPV) with
      the influence of some variables. METHODS: This cross-sectional study was
      conducted on mammograms done in one of the three main breast imaging centers in
      Oman between January 2008 and July 2012. Diagnostic and screening groups were
      identified and assessed separately. Rate of abnormal mammograms, rate of breast
      cancer and the PPV were estimated according to Breast Imaging Reporting and Data
      System (BIRADS) score, presence of breast lump and patient's age. RESULTS: Total
      of 653 mammograms were included, 254 diagnostic and 399 screening. Abnormal
      mammograms (BIRADS 4 and 5) form 31.9% of the diagnostic examinations compared
      with 6.8% of screening examinations. Breast cancer was present in 17.9% of the
      diagnostic compared with 1.0% of the screening group. The PPV of BIRADS 5 was
      94.1%, and for BIRADS 4 was 37.1 and 26.7% for diagnostic and screening studies.
      Overall PPV for abnormal mammograms was 65.2% in the diagnostic and 26.7% in the
      screening group. Mammography PPV shows positive association with age (P = 0.039)
      while presence of breast lump has no significant effect on the PPV (P = 0.38).
      CONCLUSION: BIRADS 5 score was found to have a high cancer yield making it a
      strong predictor of cancer. Different results were obtained in the diagnostic
      compared with screening mammography with higher rates of abnormal mammograms and
      breast cancer. Mammography performance should be better in the older women.

PMID- 24673797
TI  - Deleted copy number variation of Hanwoo and Holstein using next generation
      sequencing at the population level.
AB  - BACKGROUND: Copy number variation (CNV), a source of genetic diversity in
      mammals, has been shown to underlie biological functions related to production
      traits. Notwithstanding, there have been few studies conducted on CNVs using next
      generation sequencing at the population level. RESULTS: Illumina NGS data was
      obtained for ten Holsteins, a dairy cattle, and 22 Hanwoo, a beef cattle. The
      sequence data for each of the 32 animals varied from 13.58-fold to almost 20-fold
      coverage. We detected a total of 6,811 deleted CNVs across the analyzed
      individuals (average length = 2732.2 bp) corresponding to 0.74% of the cattle
      genome (18.6 Mbp of variable sequence). By examining the overlap between CNV
      deletion regions and genes, we selected 30 genes with the highest deletion
      scores. These genes were found to be related to the nervous system, more
      specifically with nervous transmission, neuron motion, and neurogenesis. We
      regarded these genes as having been effected by the domestication process.
      Further analysis of the CNV genotyping information revealed 94 putative selected
      CNVs and 954 breed-specific CNVs. CONCLUSIONS: This study provides useful
      information for assessing the impact of CNVs on cattle traits using NGS at the
      population level.

PMID- 24673800
TI  - Loss of reflex tearing after maxillary orthognathic surgery: a report of two
      cases.
AB  - BACKGROUND: Few reports have described the ophthalmic complications that occur
      after maxillary orthognathic surgery. Since cases of decreased reflex tearing
      after maxillary orthognathic surgery are extremely rare, we describe 2 cases of
      loss of reflex tearing after maxillary orthognathic surgery. CASE PRESENTATION:
      Two Asian women, an 18-year-old and a 32-year-old, suffered from unilateral
      dryness and irritation caused by maxillary orthognathic surgery. In both
      patients, Schirmer test (II) showed reduced reflex tearing in 1 eye. Computed
      tomography showed that the pterygoid plate had been fractured in both patients.
      CONCLUSIONS: The pterygopalatine ganglion and its associated fibers in the
      pterygopalatine fossa may be injured during Le Fort osteotomy.

PMID- 24673799
TI  - Suppressive expression of CD274 increases tumorigenesis and cancer stem cell
      phenotypes in cholangiocarcinoma.
AB  - Cholangiocarcinoma is an aggressive malignant tumor originating from intrahepatic
      or extrahepatic bile ducts. Its malignant phenotypes may be assumed by cancer
      stem cells (CSC). Here, we demonstrate that CD274 (PD-L1), known as an
      immunomodulatory ligand, has suppressive effects on CSC-related phenotypes of
      cholangiocarcinoma. Using two human cholangiocarcinoma cell lines, RBE and
      HuCCT1, we attempted to isolate the CD274(low) and CD274(high) cells from each
      cell line, and xenografted them into immunodeficient NOD/scid/gammacnull (NOG)
      mice. We found that the CD274(low) cells isolated from both RBE and HuCCT1 are
      highly tumorigenic in NOG mice compared with CD274(high) cells. Furthermore, the
      CD274(low) cells possess several CSC-related characteristics, such as high
      aldehyde dehydrogenase (ALDH) activity, reduced reactive oxygen species
      production and a dormant state in the cell cycle. Furthermore, depletion of CD274
      expression by shRNA in RBE cells enhances their tumorigenicity and increases ALDH
      activity. These findings are compatible with our observation that clinical
      cholangiocarcinoma specimens are classified into low and high groups for CD274
      expression, and the CD274 low group shows poorer prognosis when compared with the
      CD274 high group. These results strongly suggest that CD274 has a novel function
      in the negative regulation of CSC-related phenotypes in human cholangiocarcinoma,
      which is distinct from its immunomodulatory actions. 

PMID- 24673801
TI  - The use of publicly available quality information when choosing a hospital or
      health-care provider: the role of the GP.
AB  - BACKGROUND: Patients barely use publicly available quality information for making
      a decision concerning secondary health care, but instead rely on information
      coming from their general practitioner (GP). An intermediate role of GPs has been
      suggested concerning the use of publicly available quality information. The aim
      of the study is to quantify and explore GPs' use of publicly available quality
      information when referring patients or suggesting secondary health-care provider
      to them. METHODS: In this cross-sectional study, an invitation to an electronic
      questionnaire was sent to 858 GPs in the south of the Netherlands. GPs were asked
      about their use of and perception towards publicly available quality information
      through closed-ended and open-ended questions. Differences among subgroups were
      tested for significance using Pearson's chi-square tests. RESULTS: The majority
      of respondents (89.5%) never or rarely use publicly available quality
      information. They perceive them as invalid and unreliable. Distance to the
      hospital, prior experiences and personal contacts with specialists guide them
      when advising and referring. Almost 90% of respondents never or rarely suggest
      quality information as support for decision making to their patients. No
      significant differences between subgroups were observed. CONCLUSION: This study
      is among the firsts exploring and quantifying GPs' use of publicly available
      quality information. The results suggest that publicly available quality
      information appears in its current format and application not useful for GPs. GPs
      have to be aware of their influential role in patients' decision making and
      possibly have to take more responsibility in guiding them through the jungle of
      quality information.

PMID- 24673802
TI  - Dynamic enhancement pattern of HCC smaller than 3 cm in diameter on gadoxetic
      acid-enhanced MRI: comparison with multiphasic MDCT.
AB  - BACKGROUND & AIMS: The dynamic enhancement pattern of HCCs smaller than 3 cm in
      diameter on gadoxetic acid-enhanced magnetic resonance imaging (MRI) have not
      been extensively investigated. We aimed to evaluate the dynamic enhancement
      patterns of small HCCs (<=3 cm) on gadoxetic acid-enhanced magnetic resonance
      imaging (MRI) and compare enhancement patterns with multiphasic multidetector
      computed tomography (MDCT) based on tumour cellular differentiation and size.
      METHODS: We retrospectively included 55 patients with 67 surgically confirmed
      small HCCs (<=3 cm) who underwent multiphasic MDCT and gadoxetic acid-enhanced
      MRI. Dynamic enhancement patterns were analysed according to tumour cellular
      differentiation and size. Hepatobiliary phase images were also analysed to assess
      their additional value. RESULTS: The proportion of small HCCs demonstrating the
      typical enhancement pattern differed depending on tumour cellular differentiation
      on both MRI (P = 0.001) and MDCT (P = 0.001), but differed depending on tumour
      size only on CT (P = 0.008). Gadoxetic acid-enhanced MRI more sensitively
      depicted the typical enhancement pattern than CT for all tumours (P = 0.001), for
      moderately or poorly differentiated HCCs (P = 0.021) and for HCCs <=2 cm (P =
      0.001). 80% of tumours with atypical enhancement could be diagnosed as HCC based
      on tumour size and hepatobiliary phase images. CONCLUSIONS: On both gadoxetic
      acid-enhanced MRI and multiphasic CT, the dynamic enhancement patterns of small
      HCCs (<=3 cm) differed according to tumour cellular differentiation. Gadoxetic
      acid-enhanced MRI more frequently demonstrated the typical HCC enhancement
      pattern than CT in small HCCs.

PMID- 24673804
TI  - Forage plants as an alternative feed resource for sustainable pig production in
      the tropics: a review.
AB  - Globally, pressure on concentrate feed resources is increasing, especially in the
      tropics where many countries are net importers of food. Forage plants are a
      possible alternative, but their use as feed ingredients for pigs raises several
      issues related to their higher fibre and plant secondary metabolites contents as
      well as their lower nutritive value. In this paper, the nutritive value of
      several forage species and the parameters that influence this nutritive value in
      relationship to the plant family, the physiological stage, the plant part and the
      preservation method (fresh, hay and silage) are reviewed. The influence of the
      breed and the physiological status of the animal on animal voluntary intake of
      fibre-rich ingredients, digestibility as related to gastrointestinal volume and
      transit time and growth performances are also discussed. The final section
      highlights the advantages and drawbacks of forage plants in pig diets and
      stresses the need for proper economic evaluation to conclude on the benefits of
      the use of forage plants in pig feed. 

PMID- 24673805
TI  - Gastrointestinal motility problems in critical care: a clinical perspective.
AB  - Advances in surgery, anesthesia and intensive care have led to a dramatic
      increase in the number of patients who spend time in our intensive care units
      (ICU). Gastrointestinal (GI) motility disorders are common complications in the
      intensive care setting and are predictors of increased mortality and length of
      the stay in the ICU. Several risk factors for developing GI motility problems in
      the ICU setting have been identified and include sepsis, being on mechanical
      ventilation and the use of vasopressors, opioids or anticholinergic medications.
      Our focus is on the most common clinical manifestations of GI motor dysfunction
      in the ICU patient: gastroesophageal reflux, gastroparesis, ileus and acute
      pseudo-obstruction of the colon.

PMID- 24673806
TI  - Elevational trends in life histories: revising the pace-of-life framework.
AB  - Life-history traits in birds, such as lifespan, age at maturity, and rate of
      reproduction, vary across environments and in combinations imposed by trade-offs
      and limitations of physiological mechanisms. A plethora of studies have described
      the diversity of traits and hypothesized selection pressures shaping components
      of the survival-reproduction trade-off. Life-history variation appears to fall
      along a slow-fast continuum, with slow pace characterized by higher investment in
      survival over reproduction and fast pace characterized by higher investment in
      reproduction over survival. The Pace-of-Life Syndrome (POLS) is a framework to
      describe the slow-fast axis of variation in life-history traits and physiological
      traits. The POLS corresponds to latitudinal gradients, with tropical birds
      exhibiting a slow pace of life. We examined four possible ways that the traits of
      high-elevation birds might correspond to the POLS continuum: (i) rapid pace, (ii)
      tropical slow pace, (iii) novel elevational pace, or (iv) constrained pace.
      Recent studies reveal that birds breeding at high elevations in temperate zones
      exhibit a combination of traits creating a unique elevational pace of life with a
      central trade-off similar to a slow pace but physiological trade-offs more
      similar to a fast pace. A paucity of studies prevents consideration of the
      possibility of a constrained pace of life. We propose extending the POLS
      framework to include trait variation of elevational clines to help to investigate
      complexity in global geographic patterns. 

PMID- 24673807
TI  - CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental
      asthma exacerbations.
AB  - RATIONALE: Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We
      have shown previously that lower respiratory tract symptoms, airflow obstruction,
      and neutrophilic airway inflammation were increased in experimental RV-induced
      asthma exacerbations. OBJECTIVES: We hypothesized that neutrophil-related CXC
      chemokines and antimicrobial peptides are increased and related to clinical,
      virologic, and pathologic outcomes in RV-induced exacerbations of asthma.
      METHODS: Protein levels of antimicrobial peptides (SLPI, HNP 1-3, elafin, and LL
      37) and neutrophil chemokines (CXCL1/GRO-alpha, CXCL2/GRO-beta, CXCL5/ENA-78,
      CXCL6/GCP-2, CXCL7/NAP-2, and CXCL8/IL-8) were determined in bronchoalveolar
      lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day
      four during and 6 weeks post-experimental infection. RESULTS: BAL HNP 1-3 and
      Elafin were higher, CXCL7/NAP-2 was lower in asthmatics compared with controls at
      day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1-3 and
      CXCL8/IL-8 were increased during infection (P = 0.003 and P = 0.011,
      respectively). There was a trend to increased BAL neutrophils at day 4 compared
      with baseline (P = 0.076). BAL HNP 1-3 was positively correlated with BAL
      neutrophil numbers at day 4. There were no correlations between clinical
      parameters and HNP1-3 or IL-8 levels. CONCLUSIONS: We propose that RV infection
      in asthma leads to increased release of CXCL8/IL-8, attracting neutrophils into
      the airways where they release HNP 1-3, which further enhances airway
      neutrophilia. Strategies to inhibit CXCL8/IL-8 may be useful in treatment of
      virus-induced asthma exacerbations.

PMID- 24673803
TI  - The advantages of going large: genome-wide SNPs clarify the complex population
      history and systematics of the threatened western pond turtle.
AB  - As the field of phylogeography has matured, it has become clear that analyses of
      one or a few genes may reveal more about the history of those genes than the
      populations and species that are the targets of study. To alleviate these
      concerns, the discipline has moved towards larger analyses of more individuals
      and more genes, although little attention has been paid to the qualitative or
      quantitative gains that such increases in scale and scope may yield. Here, we
      increase the number of individuals and markers by an order of magnitude over
      previously published work to comprehensively assess the phylogeographical history
      of a well-studied declining species, the western pond turtle (Emys marmorata). We
      present a new analysis of 89 independent nuclear SNP markers and one
      mitochondrial gene sequence scored for rangewide sampling of >900 individuals,
      and compare these to smaller-scale, rangewide genetic and morphological analyses.
      Our enlarged SNP data fundamentally revise our understanding of evolutionary
      history for this lineage. Our results indicate that the gains from greatly
      increasing both the number of markers and individuals are substantial and worth
      the effort, particularly for species of high conservation concern such as the
      pond turtle, where accurate assessments of population history are a prerequisite
      for effective management. 

PMID- 24673808
TI  - Relevance of the two-component sensor protein CiaH to acid and oxidative stress
      responses in Streptococcus pyogenes.
AB  - BACKGROUND: The production of virulence proteins depends on environmental
      factors, and two-component regulatory systems are involved in sensing these
      factors. We previously established knockout strains in all suspected two
      component regulatory sensor proteins of the emm1 clinical strain of S. pyogenes
      and examined their relevance to acid stimuli in a natural atmosphere. In the
      present study, their relevance to acid stimuli was re-examined in an atmosphere
      containing 5% CO2. RESULTS: The spy1236 (which is identical to ciaHpy) sensor
      knockout strain showed significant growth reduction compared with the parental
      strain in broth at pH 6.0, suggesting that the Spy1236 (CiaHpy) two-component
      sensor protein is involved in acid response of S. pyogenes. CiaH is also
      conserved in Streptococcus pneumoniae, and it has been reported that deletion of
      the gene for its cognate response regulator (ciaRpn) made the pneumococcal
      strains more sensitive to oxidative stress. In this report, we show that the
      spy1236 knockout mutant of S. pyogenes is more sensitive to oxidative stress than
      the parental strain. CONCLUSIONS: These results suggest that the two-component
      sensor protein CiaH is involved in stress responses in S. pyogenes.

PMID- 24673809
TI  - Coacervate whey protein improves inflammatory milieu in mice fed with high-fat
      diet.
AB  - BACKGROUND: Functional foods with bioactive properties may help in treat obesity,
      as they can lead to a decreased risks of inflammatory diseases. The aim of this
      study was to investigate the effects of chitosan coacervate whey protein on the
      proinflammatory processes in mice fed with high-fat diet. METHODS: Mice were
      divided into two groups receiving either a normolipidic or high-fat diet; the
      animals in each of the two diet groups were given a diet supplement of either
      coacervate (gavage, 36 mg protein/kg of body weight) or tap water for four weeks
      [groups: normolipidic diet plus water (C); normolipidic diet and coacervate (CC);
      high-fat diet and water (H); and high-fat diet and coacervate (HC)]. RESULTS: The
      high-fat diet promoted inflammation, possibly by decreased adiponectin/sum of
      adipose tissues ratio and increased phosphorylation of NF-kappaB p50. In HC we
      observed a positive correlation between IL-10 and TNF-alpha in mesenteric adipose
      tissue, retroperitoneal adipose tissue and liver tissue. We also observed a
      positive correlation between lipopolisaccharide with IL-10 in the liver tissue.
      CONCLUSIONS: High-fat diet treatment promoted metabolic alterations and
      inflammation, and chitosan coacervate whey protein modulated inflammatory milieu.

PMID- 24673810
TI  - FCGR3B copy number loss rather than gain is a risk factor for systemic lupus
      erythematous and lupus nephritis: a meta-analysis.
AB  - AIM: Some studies have been performed to elucidate the association between Fc
      gamma receptor 3B (FCGR3B) copy number (CN) and the risk of systemic lupus
      erythematosus (SLE) and/or lupus nephritis (LN), yet the results remain
      conflicting. Therefore, we have undertaken a systematic review of all the studies
      published and carried out a meta-analysis to obtain a better understanding of the
      role of FCGR3B CN in the susceptibility of SLE and LN. METHOD: A computerized
      literature search was conducted in databases of PubMed, ISI Web of Knowledge for
      all studies investigating the association between FCGR3B CN and SLE and/or LN,
      published up to May 2013. RESULTS: A total of six articles meeting all of the
      criteria were included in this study. There were five comparisons of SLE between
      2490 patients and 4286 controls, and four comparisons of LN between 689 patients
      and 1924 controls. Our results showed that individuals with FCGR3B CN gain did
      not suffer an increased risk of SLE or LN as compared to the normal genotype in
      the total analysis (SLE: OR = 1.07, 95% CI = 0.79-1.45, P = 0.65; LN: OR = 0.83,
      95% CI = 0.47-1.46, P = 0.52). However, individuals with FCGR3B CN loss exhibited
      an increased risk of SLE or LN (SLE: OR = 1.77, 95% CI = 1.51-2.06, P < 0.00001;
      LN: OR = 2.02, 95% CI = 1.59-2.57, P < 0.00001). CONCLUSION: Our meta-analysis
      indicated that FCGR3B CN loss rather than CN gain was associated with
      susceptibility to SLE and LN.

PMID- 24673811
TI  - Prognostic evaluation of breast cancer patients with evident bone marrow
      metastasis.
AB  - In this study, we aimed to evaluate the clinicopathologic characteristics and
      prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis
      (BMM). Fifty-four BC patients, including patients with and without BMM, were
      evaluated retrospectively. In particular, the clinicopathologic features and
      survival of the patients with BMM (n = 27) were assessed and compared with the
      patients without BMM. All of the patients with BMM also had osseous metastases,
      and bone was the first site for distant recurrence in the majority of patients in
      the study group. Anemia was the most frequent symptom at presentation. The median
      time to BMM was 36.1 months (range 1.6-70.5 months, 95% CI). HER2(+) patients
      developed BMM earlier than HER2(-) patients (3.2 versus 38.3 months, 95% CI; p =
      0.05). Patients with advanced disease at the time of initial BC diagnosis
      developed BMM earlier than patients with early disease (p = 0.04). Time to
      development of BMM was significantly shorter in tumors with perinodal
      infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time
      after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis
      in patients with grade III tumors was significantly shorter than in patients with
      grade I-II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy
      after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months,
      95% CI; p < 0.001). Hormone receptor-positive, high-grade, advanced-stage tumors
      at the time of initial BC diagnosis were more common in patients with BMM.
      Invasive lobular histology was also more frequent in patients with BMM. In
      conclusion, the presence of hormone receptor-positive, multicentric, grade III,
      advanced-stage tumors may be important risk factors for the development of
      evident BMM in BC patients. Systemic single-agent chemotherapy can prolong
      survival in these patients. However, multicenter analyses are required to verify
      these findings. 

PMID- 24673812
TI  - Wild yeast harbour a variety of distinct amyloid structures with strong prion
      inducing capabilities.
AB  - Variation in amyloid structures profoundly influences a wide array of
      pathological phenotypes in mammalian protein conformation disorders and
      dominantly inherited phenotypes in yeast. Here, we describe, for the first time,
      naturally occurring, self-propagating, structural variants of a prion protein
      isolated from wild strains of the yeast Saccharomyces cerevisiae. Variants of the
      [RNQ+] prion propagating in a variety of wild yeast differ biochemically, in
      their intracellular distributions, and in their ability to promote formation of
      the [PSI+] prion. [PSI+] is an epigenetic regulator of cellular phenotype and
      adaptability. Strikingly, we find that most natural [RNQ+] variants induced
      [PSI+] at high frequencies and the majority of [PSI+] variants elicited strong
      cellular phenotypes. We hypothesize that the presence of an efficient [RNQ+]
      template primes the cell for [PSI+] formation in order to induce [PSI+] in
      conditions where it would be advantageous. These studies utilize naturally
      occurring structural variants to expand our understanding of the consequences of
      diverse prion conformations on cellular phenotypes.

PMID- 24673813
TI  - Meniscal tears: comparison of the conventional spin-echo and fast spin-echo
      techniques through image processing.
AB  - BACKGROUND: Conventional spin-echo (PD-CSE) and fast spin-echo (PD-FSE)
      techniques are frequently used to detect meniscal tears. However, the time delay
      for imaging with PD-CSE has resulted in its replacement with faster techniques,
      such as proton density fast spin-echo (PD-FSE), which has become a frequent tool
      at most diagnostic centres.Qualitative analysis shows that the PD-CSE technique
      is more sensitive, but other authors have not found significant differences
      between the aforementioned techniques. Therefore, we performed a quantitative
      analysis in this study that aims to measure differences in the quality of the
      images obtained with both techniques. METHODS: We compared the PD-CSE and PD-FSE
      techniques by quantitatively analysing the obtained proton density images: the
      area shown, as well as the brightness and lesion contrast of the obtained image.A
      set of 100 images from 50 patients thought to contain meniscal tears of the knee
      were selected. These 100 images were obtained from all individuals using both the
      PD-CSE and PD-FSE techniques. The images were processed using software developed
      in Delphi. In addition to these quantifications, three physicians, who are
      specialists in radiology and capable of analysing magnetic resonance (MR) images
      of the musculoskeletal system, qualitatively analysed the diagnostic sensitivity
      of both techniques. RESULTS: On average, samples obtained via the PD-CSE
      technique contained 22% more pixels in the lesion area. The contrast differed by
      28%, and the brightness differed by 31%. The two techniques were correlated using
      Student's t-test, which showed a statistically significant difference. The
      specialists detected meniscal tears in 30 of the images obtained via the PD-CSE
      technique, while only 72% of these cases were detected via the PD-FSE technique.
      CONCLUSIONS: The PD-CSE technique was shown to be superior to PD-FSE for all of
      the evaluated properties, making its selection preferable.

PMID- 24673814
TI  - Potential molecular signatures in epithelial ovarian cancer by genome wide
      expression profiling.
AB  - AIMS: Ovarian cancer is the deadliest of all gynecologic cancers because of its
      late diagnosis and poor treatment outcomes. This study aimed to identify
      potential molecular signatures associated with biological processes that are
      implicated in epithelial ovarian cancer (EOC). METHODS: Expression profiling was
      carried out on 16 fresh frozen EOC and normal ovarian tissue samples using the
      Illumina Whole Genome DASL assay (cDNA-mediated annealing, selection, extension
      and ligation). The differentially expressed genes were analyzed using the
      GeneSpring GX11.5 and Pathway Studio 8.0 software. The microarray results were
      validated using the immunohistochemistry analyses. RESULTS: Unpaired t-test
      identified 652 (270 up- and 382 downregulated) significant differentially
      expressed genes (P < 0.001 and fold change >=2.0). Hierarchical clustering
      analysis displayed a distinct separation of cancer and normal samples. Gene set
      enrichment analysis identified alterations in the expression of genes associated
      with cancer development and progression. Positive immunostaining of claudin-7,
      ephrin receptor A1 and Forkhead Box M1 in EOC was consistent with the
      upregulation of these genes in the microarray result. However, the positive
      immunostaining of fibroblast growth factor-7 in cancer tissues was not in
      accordance with the downregulation of this gene in the microarray result.
      CONCLUSION: These results identify significant genes and their related biological
      processes which may contribute to the better understanding of development and
      progression of epithelial ovarian cancer.

PMID- 24673815
TI  - Substrate scope and selectivity in offspring to an enzyme subjected to directed
      evolution.
AB  - We have analyzed the effects of mutations inserted during directed evolution of a
      specialized enzyme, Escherichia coli S-1,2-propanediol oxidoreductase (FucO). The
      kinetic properties of evolved variants have been determined and the observed
      differences have been rationalized by modeling the tertiary structures of
      isolated variants and the wild-type enzyme. The native substrate, S-1,2
      propanediol, as well as phenylacetaldehyde and 2S-3-phenylpropane-1,2-diol, which
      are new substrates accepted by isolated variants, were docked into the active
      sites. The study provides a comprehensive picture of how acquired catalytic
      properties have arisen via an intermediate generalist enzyme, which had acquired
      a single mutation (L259V) in the active site. Further mutagenesis of this
      generalist resulted in a new specialist catalyst. We have also been able to
      relate the native enzyme activities to the evolved ones and linked the
      differences to individual amino acid residues important for activity and
      selectivity. F254 plays a dual role in the enzyme function. First, mutation of
      F254 into an isoleucine weakens the interactions with the coenzyme thereby
      increasing its dissociation rate from the active site and resulting in a four
      fold increase in turnover number with S-1,2-propanediol. Second, F254 is directly
      involved in binding of aryl-substituted substrates via pi-pi interactions. On the
      other hand, N151 is critical in determining the substrate scope since the side
      chain amide group stabilizes binding of 1,2-substituted diols and is apparently
      necessary for enzymatic activity with these substrates. Moreover, the side chain
      of N151 introduces steric hindrance, which prevents high activity with
      phenylacetaldehyde. Additionally, the hydroxyl group of T149 is required to
      maintain the catalytically important hydrogen bonding network. 

PMID- 24673816
TI  - De novo transcriptome assembly reveals sex-specific selection acting on evolving
      neo-sex chromosomes in Drosophila miranda.
AB  - BACKGROUND: The Drosophila miranda neo-sex chromosome system is a useful resource
      for studying recently evolved sex chromosomes. However, the neo-Y genomic
      assembly is fragmented due to the accumulation of repetitive sequence.
      Furthermore, the separate assembly of the neo-X and neo-Y chromosomes into
      genomic scaffolds has proven to be difficult, due to their low level of sequence
      divergence, which in coding regions is about 1.5%. Here, we de novo assemble the
      transcriptome of D. miranda using RNA-seq data from several male and female
      tissues, and develop a bioinformatic pipeline to separately reconstruct neo-X and
      neo-Y transcripts. RESULTS: We obtain 2,141 transcripts from the neo-X and 1,863
      from the neo-Y. Neo-Y transcripts are generally shorter than their homologous neo
      X transcripts (N50 of 2,048-bp vs. 2,775-bp) and expressed at lower levels. We
      find that 24% of expressed neo-Y transcripts harbor nonsense mutation within
      their open reading frames, yet most non-functional neo-Y genes are expressed
      throughout all of their length. We find evidence of gene loss of male-specific
      genes on the neo-X chromosome, and transcriptional silencing of testis-specific
      genes from the neo-X. CONCLUSIONS: Nonsense mediated decay (NMD) has been
      implicated to degrade transcripts containing pre-mature termination codons (PTC)
      in Drosophila, but rampant description of neo-Y genes with pre-mature stop codons
      suggests that it does not play a major role in down-regulating transcripts from
      the neo-Y. Loss or transcriptional down-regulation of genes from the neo-X with
      male-biased function provides evidence for beginning demasculinization of the neo
      X. Thus, evolving sex chromosomes can rapidly shift their gene content or
      patterns of gene expression in response to their sex-biased transmission,
      supporting the idea that sex-specific or sexually antagonistic selection plays a
      major role in the evolution of heteromorphic sex chromosomes.

PMID- 24673817
TI  - Effectiveness of predicting in-hospital mortality in critically ill children by
      assessing blood lactate levels at admission.
AB  - BACKGROUND: Hyperlactatemia upon admission is a documented risk factor for
      mortality in critically ill adult patients. However, the predictive significance
      of a single lactate measurement at admission for mortality in the general
      population of critically ill children remains uncertain. This study evaluated the
      predictive value of blood lactate levels at admission and determined the cut-off
      values for predicting in-hospital mortality in the critically ill pediatric
      population. METHODS: We enrolled 1109 critically ill children who were admitted
      to a pediatric intensive care unit between July 2008 and December 2010. Arterial
      blood samples were collected in the first 2 hours after admission, and the
      lactate levels were determined. The Pediatric Risk of Mortality III (PRISM III)
      scores were calculated during the first 24 hours after admission. RESULTS: Of the
      1109 children admitted, 115 (10.4%) died in the hospital. The median
      (interquartile range) blood lactate level in critically ill children was 3.2
      mmol/l (2.2-4.8). Among the children, 859 (77.5%) had a lactate concentration
      >2.0 mmol/l. The blood lactate level upon admission was significantly associated
      with mortality (odds ratio [OR] = 1.38; 95% confidence interval [CI], 1.30-1.46;
      p <0.001), even after adjustment for age, gender, and illness severity assessed
      by PRISM III (OR = 1.27; p <0.001). Multivariate regression analysis showed that
      a high blood lactate level (OR = 1.17; 95% CI, 1.07-1.29; p = 0.001), a high
      PRISM III score (OR = 1.15; 95% CI, 1.11-1.20; p <0.001), and a low serum albumin
      (OR =0.92; 95% CI, 0.88-0.96; p <0.001) were independent risk factors for
      mortality in critically ill children. Blood lactate achieved an area under-the
      receiver-operating-characteristic curve (AUC) of 0.79 (p <0.001) for predicting
      mortality that was similar to that of PRISM III (AUC = 0.82; p <0.001). The p
      value for a comparison of both AUCs was 0.318. Blood lactate displayed a
      sensitivity of 61% and a specificity of 86% in predicting mortality at the
      optimal cut-off value of 5.55 mmol/l, and the positive and negative likelihood
      ratios were 4.5 and 0.45, respectively. CONCLUSIONS: A high blood lactate level
      at admission is independently associated with and predictive of in-hospital
      mortality in the general population of critically ill children.

PMID- 24673818
TI  - Oral iron therapy and chronic idiopathic urticaria: sideropenic urticaria?
AB  - Chronic urticaria (CU) is frequent, remains often idiopathic despite diagnostic
      efforts, and sometimes poorly responds to oral antihistamines and/or
      corticosteroids. We noticed that hyposideremia is often found in patients with
      chronic idiopathic urticaria poorly responsive to usual treatments (prCIU), and
      oral iron therapy is frequently associated to improvement or resolution of
      urticaria. Between 2003 and 2012, we observed 122 patients with prCIU, of which
      81 had moderate hyposideremia at our first visit. They continued the
      antihistamines already practiced and received oral iron therapy for 30 or 45
      days. Two months after our first visit, all had normal serum iron levels; 64
      reported complete remission of urticaria and 17 reported improvement superior to
      80%. No adverse reactions to treatment were observed. Follow-up visits confirmed
      stability of results over 6 months. Our preliminary data show that hyposideremia
      is the only abnormality in many patients with prCIU, and restoration of normal
      iron serum levels is associated to remission or remarkable clinical improvement
      of urticaria. In consideration of low cost and potential benefits for some
      patients, determination of serum levels of iron could be introduced in the
      diagnostic workup of chronic urticaria, maybe as a second-level exam in patients
      without other relevant clinical or laboratory abnormalities. 

PMID- 24673820
TI  - Transitions between child and adult mental health services: service design,
      philosophy and meaning at uncertain times.
AB  - A young person's transition of care from child and adolescent mental health
      services to adult mental health services can be an uncertain and distressing
      event that can have serious ramifications for their recovery. Recognition of this
      across many countries and recent UK media interest in the dangers of mental
      health services failing young people has led practitioners to question the
      existing processes. This paper reviews the current theories and research into
      potential failings of services and encourages exploration for a deeper
      understanding of when and how care should be managed in the transition process
      for young people. Mental health nurses can play a vital role in this process and,
      by adopting the assumptions of this paradigm, look at transition from this unique
      perspective. By reviewing the current ideas related to age boundaries, service
      thresholds, service philosophy and service design, it is argued that the
      importance of the therapeutic relationship, the understanding of the cultural
      context of the young person and the placing of the young person in a position of
      autonomy and control should be central to any decision and process of transfer
      between two mental health services.

PMID- 24673819
TI  - Antiviral activity and safety profile of silibinin in HCV patients with advanced
      fibrosis after liver transplantation: a randomized clinical trial.
AB  - Response to interferon-based therapies in HCV recurrence after liver
      transplantation (LT) is unsatisfactory, and major safety issues aroused in
      preliminary experience with boceprevir and telaprevir. As transplant community
      identified HCV viral clearance as a critical matter, efficacious and safe anti
      HCV therapies are awaited. The aim of this study was to assess efficacy and
      safety of intravenous silibinin monotherapy in patients with established HCV
      recurrence after LT, nonresponders to pegylated interferon and ribavirin. This is
      a single center, prospective, randomized, parallel-group, double-blind, placebo
      controlled, phase 2 trial including 20 patients randomly assigned (3:1) to
      receive daily 20 mg/kg of intravenous silibinin or saline as placebo, for 14
      consecutive days. On day 14 of treatment, viral load decreased by 2.30 +/- 1.32
      in silibinin group versus no change in the placebo group (P = 0.0002). Sixteen
      days after the end of the treatment, viral load mean values were similar to
      baseline. Treatment resulted well tolerated apart from a transient and reversible
      increase in bilirubin. Neither changes in immunosuppressant through levels nor
      dosage adjustments were necessary. Silibinin monotherapy has a significant
      antiviral activity in patients with established HCV recurrence on the graft not
      responding to standard therapy and confirms safety and tolerability without
      interaction with immunosuppressive drugs (ClinicalTrials.gov number:
      NCT01518933).

PMID- 24673821
TI  - The Potential Risk of Conical Implant-Abutment Connections: The Antirotational
      Ability of Cowell Implant System.
AB  - BACKGROUND: Conical implant-abutment connections are popular because of good
      antibending performance. However, the cross section is round, and the
      antirotational ability is questionable because restorations in the oral cavity
      also have to bear torsional moments resulting from chewing patterns. PURPOSE: The
      purpose of this study was to investigate the antirotational ability of conical
      implant-abutment connections with and without an index. MATERIALS AND METHODS:
      Conical connection implant system (Cowell Medi, Busan, South Korea) was selected.
      Two kinds of cyclic loading, a bending moment with (C) and without (L) a
      torsional moment, were respectively applied to two kinds of abutments, pure cone
      (N-Octa) and cone with an octagonal index (Octa). The number of cycles to fatigue
      and the failure modes was recorded. Morphologies of the abutments were examined
      with scanning electron microscopy. RESULTS: Only group C(N-Octa) passed the
      fatigue test, whereas the other three groups failed because of different failure
      modes. In group L(N-Octa), all abutments generated rotation within 150 cycles. In
      groups C(Octa) and L(Octa), all abutments fractured but in different areas.
      CONCLUSIONS: In Cowell implant system (taper angle = 7 degrees ), there was no
      antirotational ability in purely conical connections. Adding an octagonal index
      could provide an antirotational function but could compromise the antibending
      strength of the abutment.

PMID- 24673822
TI  - Non-linear recursive models for growth traits in the Pirenaica beef cattle breed.
AB  - One of the main goals of selection schemes in beef cattle populations is to
      increase carcass weight at slaughter. Live weights at different growth stages are
      frequently used as selection criteria under the hypothesis that they usually have
      a high and positive genetic correlation with weight at slaughter. However, the
      presence of compensatory growth may bias the prediction ability of early weights
      for selection purposes. Recursive models may represent an interesting alternative
      for understanding the genetic and phenotypic relationship between weight traits
      during growth. For the purposes of this study, the analysis was performed for
      three different set of data from the Pirenaica beef cattle breed: weight at 120
      days (W120) and at 210 days (W210); W120 and carcass weight at slaughter at 365
      days (CW365); W210 and CW365. The number of records for each analysis was 8592,
      4648 and 3234, respectively. A pedigree composed of 56323 individuals was also
      included. The statistical model comprised sex, year-season of birth, herd and
      slaughterhouse, plus a non-linear recursive dependency between traits. The
      dependency was modeled as a polynomial up to the 4th degree and models were
      compared using a Logarithm of Conditional Predictive Ordinates. The results of
      model comparison suggest that the best models were the 3rd degree polynomial for
      W120-W210 and W120-CW365 and the 2nd degree polynomial for W210-CW365. The
      posterior mean estimates for heritabilities ranged between 0.29 and 0.44 and the
      posterior mean estimates of the genetic correlations were null or very low,
      indicating that the relationship between traits is fully captured by the
      recursive dependency. The results imply that the predictive ability of the
      performance of future growth is low if it is only based on records of early
      weights. The usefulness of slaughterhouse records in beef cattle breeding
      evaluation is confirmed. 

PMID- 24673823
TI  - United Kingdom Myeloma Forum position statement on the use of consolidation and
      maintenance treatment in myeloma.
AB  - Therapeutic advances and the availability of novel agents have significantly
      improved outcomes in myeloma; yet, it remains incurable and strategies to improve
      survival continue to be sought. One approach is to prolong the duration of
      response and increase progression-free survival (PFS) through consolidation or
      maintenance treatment with regimens that have low toxicity profiles, and do not
      negatively impact on quality of life. Data from several studies with thalidomide,
      lenalidomide and bortezomib consistently show improvements in response and PFS,
      although results have still to be confirmed with respect to overall survival
      (OS). Despite the promising data, the optimal use of consolidation and
      maintenance treatment in terms of regimen, dose and duration has yet to be
      defined. Given the evidence to date, the UK Myeloma Forum believes that both
      maintenance and consolidation therapy should be considered as treatment options
      for patients with myeloma. Patients should be encouraged to enrol in clinical
      studies. This document reviews the current position of maintenance and
      consolidation for patients with myeloma treated in the UK. 

PMID- 24673824
TI  - Epidemiology of asexuality induced by the endosymbiotic Wolbachia across
      phytophagous wasp species: host plant specialization matters.
AB  - Among eukaryotes, sexual reproduction is by far the most predominant mode of
      reproduction. However, some systems maintaining sexuality appear particularly
      labile and raise intriguing questions on the evolutionary routes to asexuality.
      Thelytokous parthenogenesis is a form of spontaneous loss of sexuality leading to
      strong distortion of sex ratio towards females and resulting from mutation,
      hybridization or infection by bacterial endosymbionts. We investigated whether
      ecological specialization is a likely mechanism of spread of thelytoky within
      insect communities. Focusing on the highly specialized genus Megastigmus
      (Hymenoptera: Torymidae), we first performed a large literature survey to examine
      the distribution of thelytoky in these wasps across their respective obligate
      host plant families. Second, we tested for thelytoky caused by endosymbionts by
      screening in 15 arrhenotokous and 10 thelytokous species for Wolbachia,
      Cardinium, Arsenophonus and Rickettsia endosymbionts and by performing antibiotic
      treatments. Finally, we performed phylogenetic reconstructions using multilocus
      sequence typing (MLST) to examine the evolution of endosymbiont-mediated
      thelytoky in Megastigmus and its possible connections to host plant
      specialization. We demonstrate that thelytoky evolved from ancestral arrhenotoky
      through the horizontal transmission and the fixation of the parthenogenesis
      inducing Wolbachia. We find that ecological specialization in Wolbachia's hosts
      was probably a critical driving force for Wolbachia infection and spread of
      thelytoky, but also a constraint. Our work further reinforces the hypothesis that
      community structure of insects is a major driver of the epidemiology of
      endosymbionts and that competitive interactions among closely related species may
      facilitate their horizontal transmission. 

PMID- 24673825
TI  - Homozygous expression of fetal red cell antigen in donor oocyte pregnancy
      complicated by allo-immunisation: are current antibody thresholds to trigger
      increased monitoring relevant?

PMID- 24673826
TI  - Selective splenic artery embolization for the treatment of thrombocytopenia and
      hypersplenism in paroxysmal nocturnal hemoglobinuria.
AB  - BACKGROUND: PNH is associated with abdominal vein thrombosis, which can cause
      splenomegaly and hypersplenism. The combination of thrombosis, splenomegaly, and
      thrombocytopenia (TST) is challenging because anticoagulants are indicated but
      thrombocytopenia may increase the bleeding risk. Splenectomy could alleviate
      thrombocytopenia and reduce portal pressure, but it can cause post-operative
      thromboses and opportunistic infections. We therefore sought to determine whether
      selective splenic artery embolization (SSAE) is a safe and effective alternative
      to splenectomy for TST in patients with PNH. METHODS: Four patients with PNH and
      TST received successive rounds of SSAE. By targeting distal vessels for
      occlusion, we aimed to infarct approximately 1/3 of the spleen with each
      procedure. RESULTS: Three of 4 patients had an improvement in their platelet
      count, and 3 of 3 had major improvement in abdominal pain/discomfort. The one
      patient whose platelet count did not respond had developed marrow failure, and
      she did well with an allo-SCT. Post-procedure pain and fever were common and
      manageable; only one patient developed a loculated pleural effusion requiring
      drainage. One patient, who had had only a partial response to eculizumab,
      responded to SSAE not only with an improved platelet count, but also with an
      increase in hemoglobin level and decreased transfusion requirement. CONCLUSIONS:
      These data indicate that SSAE can decrease spleen size and reverse hypersplenism,
      without exposing the patient to the complications of splenectomy. In addition,
      SSAE probably reduces the uptake of opsonised red cells in patients who have had
      a limited response to eculizumab, resulting in an improved quality of life for
      selected patients.

PMID- 24673827
TI  - The -308 G/A polymorphism in the tumor necrosis factor-alpha gene is not
      associated with development and progression of rheumatoid arthritis in
      Argentinean patients.
AB  - AIM: A polymorphism in the tumor necrosis factor-alpha (TNF-alpha) promoter
      region has been associated with disease susceptibility and progression in
      rheumatoid arthritis (RA). The presence of an adenosine (TNF2 allele) instead of
      a guanine (TNF1 allele) at position -308 may be responsible for a general
      increase in the transcriptional activity of the TNF-alpha gene. Our aim was to
      evaluate the association of the TNF2 allele with the risk of disease development
      and/or progression of RA in an Argentine population cohort. METHODS: Two hundred
      and twenty-three consecutive patients with RA according to the 1987 criteria of
      the American College of Rheumatology were included in the study. Clinical
      variables, Disease Activity Score 28, Health Assessment Questionnaire and
      Rheumatoid Arthritis Quality of Life were recorded. The radiographic erosions
      were determined by the method of Sharp/van der Heijde. A group of 111 healthy
      subjects matched by sex and age was used as a control. All samples were genotyped
      for the -308 G/A TNF-alpha polymorphism. RESULTS: No significant differences were
      observed either in the frequency of the TNF2 allele or in the genotypic
      distributions of the -308 G/A TNF-alpha polymorphism (P > 0.05) between the
      control group and the RA patients. No association was found between the TNF2
      allele and the variables related to the course and outcome of the disease (P >
      0.05). CONCLUSION: In this cohort of Argentinean patients with RA, the TNF2
      allele was neither associated with susceptibility to the disease nor was it
      associated with the variables related to the course and outcome of the disease.

PMID- 24673828
TI  - Mutual learning and reverse innovation--where next?
AB  - There is a clear and evident need for mutual learning in global health systems.
      It is increasingly recognized that innovation needs to be sourced globally and
      that we need to think in terms of co-development as ideas are developed and
      spread from richer to poorer countries and vice versa. The Globalization and
      Health journal's ongoing thematic series, "Reverse innovation in global health
      systems: learning from low-income countries" illustrates how mutual learning and
      ideas about so-called "reverse innovation" or "frugal innovation" are being
      developed and utilized by researchers and practitioners around the world. The
      knowledge emerging from the series is already catalyzing change and challenging
      the status quo in global health. The path to truly "global innovation flow",
      although not fully established, is now well under way. Mobilization of knowledge
      and resources through continuous communication and awareness raising can help
      sustain this movement. Global health learning laboratories, where partners can
      support each other in generating and sharing lessons, have the potential to
      construct solutions for the world. At the heart of this dialogue is a focus on
      creating practical local solutions and, simultaneously, drawing out the lessons
      for the whole world. 

PMID- 24673829
TI  - Bilateral extramedullary plasmacytoma of the breast.

PMID- 24673830
TI  - Amantadine, an N-Methyl-D-Aspartate antagonist, for treatment of chronic
      neuropathic pain in a dog.

PMID- 24673831
TI  - Mussels as a tool for mitigation of nutrients in the marine environment.
AB  - Long-line mussel farming has been proposed as a mitigation tool for removal of
      excess nutrients in eutrophic coastal waters. A full-scale mussel farm optimized
      for cost efficient nutrient removal was established in the eutrophic Skive Fjord,
      Denmark where biological and economic parameters related to nutrient removal was
      monitored throughout a full production cycle (1 yr). The results showed that it
      was possible to obtain a high area specific biomass of 60 t WW ha(-1) eqvivalent
      to a nitrogen and phosphorus removal of 0.6-0.9 and 0.03-0.04 t ha(-1)yr,
      respectively. The analysis of the costs related to establishment, maintenance and
      harvest revealed that mussel production optimized for mitigation can be carried
      out at a lower cost compared to mussel production for (human) consumption. The
      costs for nutrient removal was 14.8 ? kg(-1)N making mitigation mussel production
      a cost-efficient measure compared to the most expensive land-based measures.

PMID- 24673833
TI  - Regulation of amino sugar utilization in Bacillus subtilis by the GntR family
      regulators, NagR and GamR.
AB  - In Bacillus subtilis separate sets of genes are implicated in the transport and
      metabolism of the amino sugars, glucosamine and N-acetylglucosamine. The genes
      for use of N-acetylglucosamine (nagAB and nagP) are found in most firmicutes and
      are controlled by a GntR family repressor NagR (YvoA). The genes for use of
      glucosamine (gamAP) are repressed by another GntR family repressor GamR (YbgA).
      The gamR-gamAP synton is only found in B. subtilis and a few very close
      relatives. Although NagR and GamR are close phylogenetically, there is no cross
      regulation between their operons. GlcN6P prevents all binding of GamR to its
      targets. NagR binds specifically to targets containing the previously identified
      dre palindrome but its binding is not inhibited by GlcN6P or GlcNAc6P. GamR-like
      binding sites were also found in some other Bacilli associated with genes for use
      of chitin, the polymer of N-acetylglucosamine, and with a gene for another GamR
      homologue (yurK). We show that GamR can bind to two regions in the chi operon of
      B. licheniformis and that GamR and YurK are capable of heterologous regulation.
      GamR can repress the B. licheniformis licH-yurK genes and YurK can repress B.
      subtilis gamA. 

PMID- 24673832
TI  - Activating transcription factor 4 regulates adipocyte differentiation via
      altering the coordinate expression of CCATT/enhancer binding protein beta and
      peroxisome proliferator-activated receptor gamma.
AB  - Adipose tissue is crucial for energy homeostasis and is a topic interest with
      respect to investigating the regulation of adipose tissue formation for the ever
      increasing health concerns of obesity and type 2 diabetes. Adipocyte
      differentiation is tightly regulated by the characteristic sequential expression
      change of adipocyte genes, including members of the CCATT/enhancer binding
      protein (C/EBP) family of transcription factors, peroxisome proliferator
      activated receptor gamma and tribbles homolog 3. In the present study, we
      demonstrate that C/EBPbeta and peroxisome proliferator-activated receptor gamma
      (but not tribbles homolog 3) are targeted for activation by activating
      transcription factor 4 (ATF4), a member of cAMP response element
      binding/activator transcription factor family. Importantly, overexpression of
      ATF4 in 3T3-L1 cells enhanced adipogenesis, whereas small-interfering ATF4
      blocked conversion of preadipocytes to adipocytes. These findings were
      accomplished by altering the coordinate expression of adipogenic transcription
      factors. Taken together, our results suggest that ATF4 is a positive regulator of
      adipocyte differentiation. This notion is also supported by the results of the
      present study showing that the expression of ATF4 is induced during adipocyte
      differentiation. Thus, ATF4 could be an important regulator of energy
      homeostasis. 

PMID- 24673834
TI  - Accelerometer-determined physical activity and self-reported health in a
      population of older adults (65-85 years): a cross-sectional study.
AB  - BACKGROUND: The link between physical activity (PA) and prevention of disease,
      maintenance of independence, and improved quality of life in older adults is
      supported by strong evidence. However, there is a lack of data on population
      levels in this regard, where PA level has been measured objectively. The main
      aims were therefore to assess the level of accelerometer-determined PA and to
      examine its associations with self-reported health in a population of Norwegian
      older adults (65-85 years). METHODS: This was a part of a national multicenter
      study. Participants for the initial study were randomly selected from the
      national population registry, and the current study included those of the initial
      sample aged 65-85 years. The ActiGraph GT1M accelerometer was used to measure PA
      for seven consecutive days. A questionnaire was used to register self-reported
      health. Univariate analysis of variance with Bonferroni adjustments were used for
      comparisons between multiple groups. RESULTS: A total of 560 participants had
      valid activity registrations. Mean age (SD) was 71.8 (5.6) years for women
      (n=282) and 71.7 (5.2) years for men (n=278). Overall PA level (cpm) differed
      considerably between the age groups where the oldest (80-85 y) displayed a 50%
      lower activity level compared to the youngest (65-70 y). No sex differences were
      observed in overall PA within each age group. Significantly more men spent time
      being sedentary (65-69 and 70-74 years) and achieved more minutes of moderate to
      vigorous PA (MVPA) (75-79 years) compared to women. Significantly more women
      (except for the oldest), spent more minutes of low-intensity PA compared to men.
      PA differed across levels of self-reported health and a 51% higher overall PA
      level was registered in those, with "very good health" compared to those with
      "poor/very poor health". CONCLUSION: Norwegian older adults PA levels differed by
      age. Overall, the elderly spent 66% of their time being sedentary and only 3% in
      MVPA. Twenty one percent of the participants fulfilled the current Norwegian PA
      recommendations. Overall PA levels were associated with self-reported health.

PMID- 24673835
TI  - Dairy consumption and risk of esophageal squamous cell carcinoma: A meta-analysis
      of observational studies.
AB  - AIM: Inconsistent results regarding the relations between consumption of dairy
      products and the risk of esophageal squamous cell carcinoma (ESCC) have been
      reported. In this report, we summarized the evidence by a meta-analysis of
      observational studies. METHODS: Eligible studies published up to January 31, 2013
      were retrieved via both computer searches and a manual review of references.
      Random-effects models were used to calculate the summary relative risk (SRR)
      based on high versus low and dose-response analysis. RESULTS: A total of 19
      studies with 4315 ESCC cases were included in this meta-analysis. Overall, there
      were no significant associations between intakes of total dairy products, milk,
      cheese and butter and ESCC for the highest versus lowest intake categories (total
      dairy products: SRR 1.03, 95% confidence interval [CI]: 0.60-1.77; milk: SRR
      0.93, 95% CI: 0.74-1.16; cheese: SRR 0.84, 95% CI: 0.61-1.15; butter: SRR 1.77,
      95% CI 0.85-3.75). A significant inverse association was found for yogurt
      consumption (SRR 0.73, 95% CI: 0.54-0.98). There was high heterogeneity among
      studies on total dairy products, milk and butter; however, little or no
      heterogeneity was observed among studies on cheese and yogurt. CONCLUSION: No
      associations between consumption of milk, dairy products, butter or cheese and
      risk of ESCC were found, while yogurt consumption may have a protective effect.
      However, these associations may be subject to high levels of heterogeneity or
      confounding, and further efforts should be made to confirm these findings.

PMID- 24673836
TI  - Anaesthetic efficacy of bupivacaine 2-hydroxypropyl-beta-cyclodextrin for dental
      anaesthesia after inferior alveolar nerve block in rats.
AB  - Bupivacaine is a long-acting local anaesthetic that is widely used in medicine
      and dentistry. The duration and intensity of its sensory blockade in animal
      models is increased by its inclusion in complexes with cyclodextrins. The aim of
      the present study was to evaluate the anaesthetic efficacy of bupivacaine 2
      hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complex for dental
      anaesthesia after inferior alveolar nerve block in rats. Thirty rats were each
      given an injection close to the mandibular foramen of 0.2ml of one of the
      following formulations: 0.5% bupivacaine alone; 0.5% bupivacaine with 1:200,000
      epinephrine; and 0.5% bupivacaine-HPbetaCD inclusion complex (bupivacaine
      HPbetaCD). The other sides were used as controls, with either 0.9% saline or
      anaesthetic-free HPbetaCD solution being injected. The onset, success, and
      duration of pulpal anaesthesia were assessed by electrical stimulation ("pulp
      tester") on inferior molars. Results were analysed using ANOVA (Tukey), log rank,
      and chi square tests (alpha=5%). There were no differences among the formulations
      in onset of anaesthesia (p=0.59) or between the bupivacaine plus epinephrine and
      bupivacaine plus HPbetaCD in duration of anaesthesia, but bupivacaine plus
      epinephrine gave significantly higher values than bupivacaine alone (p=0.007).
      Bupivacaine plus epinephrine was a better anaesthetic than bupivacaine alone
      (p=0.02), while Bupi-HPbetaCD gave intermediate results, and therefore did not
      differ significantly from the other 2 groups (p=0.18 with bupivacaine alone; and
      p=0.44 with bupivacaine plus epinephrine). The bupivacaine-HPbetaCD complex
      showed similar anaesthetic properties to those of bupivacaine with epinephrine. 

PMID- 24673837
TI  - High throughput sequencing of two celery varieties small RNAs identifies
      microRNAs involved in temperature stress response.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs of 20 to 24 nucleotides
      that regulate gene expression and responses to biotic and abiotic stress. Till
      now, no reports have previously been published concerning miRNAs in celery.
      RESULTS: Two small RNAs libraries were constructed from two celery varieties,
      'Jinnan Shiqin' and 'Ventura', and characterized by deep sequencing. A total of
      431 (418 known and 13 novel) and 346 (341 known and five novel) miRNAs were
      identified in celery varieties 'Jinnan Shiqin' and 'Ventura', respectively.
      Potential miRNA-target genes were predicted and annotated by screening diverse
      protein databases, including Gene Ontology, Cluster of Orthologous Groups and
      Kyoto Encyclopedia of Genes and Genomes. Significant differential expression
      between the two varieties was seen for 221 miRNAs. qRT-PCR was used to analyze
      the abundance of six miRNAs under cold and heat stress conditions. The results
      showed that miRNAs may have important functions in controlling temperature stress
      in celery. CONCLUSION: A large number of miRNAs were identified in celery, and
      their target genes, functional annotations, and gene expression patterns have
      been explored.These findings provide the first information on celery miRNAs and
      enhance understanding of celery miRNA regulatory mechanisms under extreme
      temperature stress.

PMID- 24673838
TI  - Mental health inequalities in Slovenian 15-year-old adolescents explained by
      personal social position and family socioeconomic status.
AB  - INTRODUCTION: Mental health inequalities are an increasingly important global
      problem. This study examined the association between mental health status and
      certain socioeconomic indicators (personal social position and the socioeconomic
      status of the family) in Slovenian 15-year-old adolescents. METHODS: Data
      originate from the WHO-Collaborative cross-national 'Health Behavior in School
      aged Children' study conducted in Slovenia in 2010 (1,815 secondary school
      pupils, aged 15). Mental health status was measured by: KIDSCREEN-10, the
      Strength and Difficulties questionnaire (SDQ), a life satisfaction scale, and one
      question about feelings of depression. Socioeconomic position was measured by the
      socioeconomic status of the family (Family Affluence Scale, perceived material
      welfare, family type, occupational status of parents) and personal social
      position (number of friends and the type of school). Logistic regression and a
      multivariate analysis of variance (MANOVA) were performed. RESULTS: Girls had 2.5
      times higher odds of suffering feelings of depression (p < 0.001), 1.5-times
      higher odds of low life satisfaction (p = 0.008), and a greater chance of a lower
      quality of life and a higher SDQ score than boys (p = 0.001). The adolescents who
      perceived their family's material welfare as worse had 4-times higher odds (p <
      0.001) of a low life satisfaction, a greater chance of a low quality of life, and
      a higher SDQ score than those who perceived it as better (p < 0.001). Adolescents
      with no friends had lower KIDSCREEN-10 and higher SDQ scores than those who had
      more than three friends. CONCLUSIONS: Despite the fact that Slovenia is among the
      EU members with the lowest rates of social inequalities, it was found that
      adolescents with a lower socioeconomic position have poorer mental health than
      those with a higher socioeconomic position. Because of the financial crisis, we
      can expect an increase in social inequalities and a greater impact on
      adolescents' mental health status in Slovenia in the future.

PMID- 24673839
TI  - The impact of an educational mental health intervention on adolescents'
      perceptions of mental illness.
AB  - Nowadays, in many countries, mental health care is primarily community based.
      Community perceptions of mental illness are an essential issue for the quality of
      life of people with mental health problems and the promotion of mental health in
      general. The aim of this study was to explore adolescents' perceptions of mental
      illness and to examine the extent to which those perceptions changed after an
      educational mental health intervention. The data were collected twice, before and
      after the educational mental health intervention. Fifty-nine pupils from two
      Greek secondary schools were individually interviewed, and data were analyzed by
      inductive content analysis. The findings show that adolescents can provide a rich
      description of mental illness in a multidimensional way. After the intervention,
      they provide different descriptions, identify various forms of mental illness and
      express opinions on what mentally ill people need and how they should be treated.
      It is concluded that mental health educational interventions in schools can be
      effective in changing adolescents' perceptions towards mental illness.

PMID- 24673840
TI  - Enhanced brain small-worldness after sleep deprivation: a compensatory effect.
AB  - Sleep deprivation has a variable impact on extrinsic activities during multiple
      cognitive tasks, especially on mood and emotion processing. There is also a trait
      like individual vulnerability or compensatory effect in cognition. Previous
      studies have elucidated the altered functional connectivity after sleep
      deprivation. However, it remains unclear whether the small-world properties of
      resting-state network are sensitive to sleep deprivation. A small-world network
      is a type of graph that combines a high local connectivity as well as a few long
      range connections, which ensures a higher information-processing efficiency at a
      low cost. The complex network of the brain can be described as a small-world
      network, in which a node is a brain region and an edge is present when there is a
      functional correlation between two nodes. Here, we investigated the topological
      properties of the human brain networks of 22 healthy subjects under sufficient
      sleep and sleep-deprived conditions. Specifically, small-worldness is utilized to
      quantify the small-world property, by comparing the clustering coefficient and
      path length of a given network to an equivalent random network with same degree
      distribution. After sufficient sleep, the brain networks showed the property of
      small-worldness. Compared with the resting state under sufficient sleep, the
      small-world property was significantly enhanced in the sleep deprivation
      condition, suggesting a possible compensatory adaptation of the human brain.
      Specifically, the altered measurements were correlated with the neuroticism of
      subjects, indicating that individuals with low-levels of neuroticism are more
      resilient to sleep deprivation.

PMID- 24673841
TI  - Maternal influence on feeding site selection of male and female lambs.
AB  - We conducted an experiment to determine whether early-life social learning of
      feeding site selection in lambs was sex-specific. Sixteen ewes and their new born
      lambs were used in a controlled experiment. Eight ewe-lamb pairs included a male
      lamb and the remaining eight a female lamb. All pairs were individually exposed
      to an experimental arena containing a safe and unsafe artificial feeding site
      (SFS, UFS) each consisting of nine bowls which contained either ground Bermuda
      grass hay (SFS) or ground alfalfa hay (UFS). The bowls in UFS were surrounded by
      bright orange traffic cones (visual cues). Half the ewes were trained with
      controlled electric shock to avoid UFS. Thus, pairs were randomly assigned to:
      (1) shock aversion training (SAT) to mothers of male lambs (MS); (2) SAT to
      mothers of female lambs (FS); (3) no aversion training (NAT, control) to mothers
      of male lambs (MC); and (4) NAT (control) to mothers of female lambs (FC). None
      of the lambs were subjected to SAT. During training, testing, extinction, and
      retraining ewe-lamb pairs were exposed to the arena together. Ewes were then
      removed from the experiment and two additional extinction phases were conducted
      with weaned lambs alone. Fear conditioning elicited UFS avoidance of both the
      trained ewes (means+/-s.e.m. % times observed in UFS during testing phase:
      FC=95.3+/-1.70; MC=94.4+/-4.87; FS=1.6+/-1.63; MS=0 +/-0; P<0.01) and their naive
      lambs (FC=83.8+/-6.07%; MC=76.6+/-6.56%; FS=30.4+/-7.90%; MS=33.9+/-9.23%;
      P<0.01). UFS avoidance in lambs occurred regardless of sex and tended to persist
      after weaning (% times observed in UFS during 1st post-weaning extinction phase:
      FC=92.6+/-4.50%; MC=89.8+/-6.09%; FS=45.1+/-10.57%; MS=43.5+/-10.42%; P=0.06).
      Fear conditioning in mothers appeared to alter sex-related differences in mother
      infant behavioral synchrony by increasing and decreasing feeding synchrony of
      male and female lambs, respectively (FC: r=0.52, P<0.01; MC: r=-0.02, P=0.86; FS:
      r=0.14, P=0.26; MS: r=0.46, P<0.01). During the extinction phase mothers of ram
      lambs were observed feeding more often (FC=85.0+/-2.33%; MC=92.7+/-1.45%;
      FS=47.3+/-8.81%; MS=72+/-5.68%; P=0.02) and standing less often than ewes with
      daughters (FC=7.3+/-2.40%; MC=2.7+/-0.83%; FS=39.3+/-9.04%; MS=18.0+/-5.29%;
      P=0.06). This study suggests that social conditioning at an early age could be a
      viable tool to induce learning of feeding site avoidance in female and male lambs
      alike. 

PMID- 24673842
TI  - Clinical significance of gastrointestinal bleeding after living donor liver
      transplantation.
AB  - The clinical presentations of gastrointestinal bleeding (GIB) occurring after
      living donor liver transplantation (LDLT) have not been fully described. We
      performed a retrospective analysis of 297 LDLT cases. Nineteen patients (6.4%)
      experienced GIB after LDLT. The etiology of GIB included bleeding at the
      jejunojejunostomy following hepaticojejunostomy (n = 13), peptic ulcer disease (n
      = 2), portal hypertensive gastropathy (n = 2), and other causes (n = 2).
      Hemostasis was achieved in 13 patients (68.4%) by endoscopic (n = 3), surgical (n
      = 1), or supportive treatments (n = 15), but not in the other six patients. Graft
      dysfunction (P < 0.001), hepaticojejunostomy (P = 0.01), portal vein pressure at
      the end of surgery >20 mmHg (P = 0.002), and operative blood loss >10 L (P =
      0.004) were risk factors. One-year graft survival rate was significantly lower in
      patients with GIB than in patients without GIB (P < 0.001). The inhospital
      mortality rate was 52.6% for patients with GIB, 75.0% for patients with graft
      dysfunction, and 14.3% for patients without graft dysfunction (P = 0.028).
      Despite its infrequency after LDLT, GIB has strong correlation with graft
      dysfunction and inhospital mortality.

PMID- 24673843
TI  - Localized pagetoid reticulosis (Woringer-Kolopp disease) completely response to
      NB-UVB combined with IFN.
AB  - A cutaneous lymphoproliferative disorder, localized pagetoid reticulosis (LPR),
      is rare but distinctive in its clinical and histopathological manifestations.
      Without an evidence-based medicine treatment guideline because of extremely low
      incidence, LPR poses a therapeutic challenge. We describe a 67-year-old Chinese
      woman with LRP who showed complete response to narrow-band ultraviolet B combined
      with intramuscular interferon alpha-2b. 

PMID- 24673844
TI  - Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy:
      targeting the renal tubule in diabetes.
AB  - Optimal prevention and treatment of chronic kidney disease in diabetes requires
      implementing therapies that specifically interfere with the pathogenesis of
      diabetic nephropathy. In this regard, significant attention has been given to
      alterations of the proximal tubule and resulting changes in glomerular filtration
      rate. At the onset of diabetes mellitus, hyperglycemia causes increases in
      proximal tubular reabsorption secondary to induction of tubular growth with
      associated increases in sodium/glucose cotransport. The increase in proximal
      reabsorption leads to a decrease in solute load to the macula densa, deactivation
      of the tubuloglomerular feedback, and increases in glomerular filtration rate.
      Because glomerular hyperfiltration currently is recognized as a risk factor for
      progression of kidney disease in diabetic patients, limiting proximal tubular
      reabsorption constitutes a potential target to reduce hyperfiltration. The recent
      introduction of sodium/glucose cotransporter 2 (SGLT2) inhibitors opens new
      therapeutic perspectives for this high-risk patient population. Experimental
      studies have shown that these new agents attenuate the progressive nature of
      diabetic nephropathy by blood glucose-dependent and -independent mechanisms.
      SGLT2 inhibition may prevent glomerular hyperfiltration independent of the effect
      of lowering blood glucose levels while limiting kidney growth, inflammation, and
      albuminuria through reductions in blood glucose levels. Clinical data for the
      potential role of the proximal tubule in the pathophysiology of diabetic
      nephropathy and the nephroprotective effects of SGLT2 inhibitors currently are
      limited compared to the more extensive experimental literature. We review the
      evidence supporting this working hypothesis by integrating the experimental
      findings with the available clinical data. 

PMID- 24673845
TI  - Linear Measurement Accuracy of Eight Cone Beam Computed Tomography Scanners.
AB  - BACKGROUND: Information regarding linear accuracy is necessary for efficient
      treatment evaluation, especially for maxillofacial reconstruction or implants.
      PURPOSE: To investigate the accuracy of linear measurements from multiple cone
      beam computed tomography (CBCT) devices. MATERIALS AND METHODS: A RANDO(r)
      phantom was scanned with eight CBCT scanners (11 modes). The viewing software
      accompanying each scanner was employed for measurements in mediolateral,
      anteroposterior, and supero-inferior dimensions by two dentomaxillofacial
      radiologists. Digital caliper measurements were used as a "gold standard." ANOVA
      with Scheffe post hoc analysis and intraclass correlation coefficient (ICC) were
      utilized for statistical analyses. The level of confidence was 95%. RESULTS:
      Differences from the gold standard among 11 acquisition modes were statistically
      significant (p < .001). Measurements from one unit were always underestimated
      compared with all others (p < .001). The range of absolute measurement errors for
      tested units was -2.56 to 0.54 mm (mean +/- SD 0.45 +/- 0.71) including the
      outlier and -0.34 to 0.54 mm (0.16 +/- 0.11) excluding the outlier. Slightly more
      values were underestimated than overestimated (41 of 66 measurements, 7 out of 11
      CBCT modes). ICC scores for inter- and intraobserver agreement were perfect
      (1.000). CONCLUSIONS: Treatment planning from large-volume CBCT was found to be
      reliable in all except one of the investigated scanners. New CBCT scanners should
      always be tested for geometric accuracy.

PMID- 24673846
TI  - Traditional Tar Production from the Anatolian Black Pine [Pinus nigra Arn. subsp.
      pallasiana (Lamb.) Holmboe var. pallasiana] and its usages in Afyonkarahisar,
      Central Western Turkey.
AB  - BACKGROUND: Tar is one example of a plant product used in folk medicine and it is
      obtained from Pinus nigra Arn. subsp. pallasiana (Lamb.) Holmboe, which is very
      common in the West Anatolian Region. Old trees that are good for kindling and
      have thick trucks are preferred to obtain tar. Tar is used not only as
      traditional medicine but also for protection against both endoparasites and
      ectoparasites. The objective of this study was to record the traditional method
      of obtaining tar and its usages in Afyonkarahisar which is located in the Western
      Anatolian Region of Turkey. METHODS: In order to record the traditional methods
      of obtaining tar, we visited the villages of Doglat, Kurtyurdu and Catagil in
      Afyonkarahisar (Turkey) June-July, 2012. Ethnobotanical data about the method of
      collection and traditional usages of tar were obtained through informal
      interviews with 26 participants (16 men and 10 women). Data concerning the method
      of tar collection and its traditional usages were recorded and photographed.
      RESULTS: The traditional method for obtaining tar from Pinus nigra subsp.
      pallasiana by local people was recorded and the local usages (curing ear pain in
      children, osteomyelitis, wounds, ulcers, eczema, acne, alopecia, fungus, foot-and
      mouth disease in animals, mouth sores in sheep and goats, protection against endo
      and ectoparasites, repellent for snakes, mice, flies (Tabanus bovinus) and
      ticks, and the prevention of water leakage from roofs) of tar are described.
      CONCLUSION: In this study, the traditional method for obtaining tar and the
      traditional usages of tar are explained. Documentation of the method of obtaining
      tar and its traditional usages may contribute to scientific research on the
      benefits and usages of tar in medicine, veterinary medicine, as well as other
      fields.

PMID- 24673847
TI  - Long-term breast cancer survival in Vietnamese women.

PMID- 24673848
TI  - Identification and characterization of LFD1, a novel protein involved in membrane
      merger during cell fusion in Neurospora crassa.
AB  - Despite its essential role in development, molecular mechanisms of membrane
      merger during cell-cell fusion in most eukaryotic organisms remain elusive. In
      the filamentous fungus Neurospora crassa, cell fusion occurs during asexual spore
      germination, where genetically identical germlings show chemotropic interactions
      and cell-cell fusion. Fusion of germlings and hyphae is required for the
      formation of the interconnected mycelial network characteristic of filamentous
      fungi. Previously, a multipass membrane protein, PRM1, was characterized and acts
      at the step of bilayer fusion in N. crassa. Here we describe the identification
      and characterization of lfd-1, encoding a single pass transmembrane protein,
      which is also involved in membrane merger. lfd-1 was identified by a targeted
      analysis of a transcriptional profile of a transcription factor mutant (Deltapp
      1) defective in germling fusion. The Deltalfd-1 mutant shows a similar, but less
      severe, membrane merger defect as a DeltaPrm1 mutant. By genetic analyses, we
      show that LFD1 and PRM1 act independently, but share a redundant function. The
      cell fusion frequency of both Deltalfd-1 and DeltaPrm1 mutants was sensitive to
      extracellular calcium concentration and was associated with an increase in cell
      lysis, which was suppressed by a calcium-dependent mechanism involving a
      homologue to synaptotagmin. 

PMID- 24673849
TI  - How to restore chromatin structure and function in response to DNA damage--let
      the chaperones play: delivered on 9 July 2013 at the 38th FEBS Congress in St
      Petersburg, Russia.
AB  - Histone deposition onto DNA assisted by specific chaperones forms the chromatin
      basic unit and serves to package the genome within the cell nucleus. The
      resulting chromatin organization, often referred to as the epigenome, contributes
      to a unique transcriptional program that defines cell identity. Importantly,
      during cellular life, substantial alterations in chromatin structure may arise
      due to cell stress, including DNA damage, which not only challenges the integrity
      of the genome but also threatens the epigenome. Considerable efforts have been
      made to decipher chromatin dynamics in response to genotoxic stress, and to
      assess how it affects both genome and epigenome stability. Here, we review recent
      advances in understanding the mechanisms of DNA damage-induced chromatin
      plasticity in mammalian cells. We focus specifically on the dynamics of histone
      H3 variants in response to UV irradiation, and highlight the role of their
      dedicated chaperones in restoring both chromatin structure and function. Finally,
      we discuss how, in addition to restoring chromatin integrity, the cellular
      networks that signal and repair DNA damage may also provide a window of
      opportunity for modulating the information conveyed by chromatin. 

PMID- 24673850
TI  - Bowel disorders and its spatial trend in Manitoba, Canada.
AB  - BACKGROUND: Bowel disorders have destructive impacts on the patients social and
      mental aspects of life and can cause emotional distress. The risk of developing
      bowel incontinence also increases with age. The rate of incidence of inflammatory
      bowel disease in Manitoba, Canada, has been unusually raised. Therefore, it is
      important to identify trends in the incidence of bowel disorders that may suggest
      further epidemiological studies to identify risk factors and identify any changes
      in important factors. METHODS: An important part of spatial epidemiology is
      cluster detection as it has the potential to identify possible risk factors
      associated with disease, which in turn may lead to further investigations into
      the nature of diseases. To test for potential disease clusters many methods have
      been proposed. The focused detection methods including the circular spatial scan
      statistic (CSS), flexible spatial scan statistic (FSS), and Bayesian disease
      mapping (BYM) are among the most popular disease detection procedures. A
      frequentist approach based on maximum likelihood estimation (MLE) has been
      recently used to identify potential focused clusters as well. The aforementioned
      approaches are studied by analyzing a dataset of bowel disorders in the province
      of Manitoba, Canada, from 2001 to 2010. RESULTS: The CSS method identified less
      regions than the FSS method in the south part of the province as potential
      clusters. The same regions were identified by the BYM and MLE methods as being
      potential clusters of bowel disorders with a slightly different order of
      significance. Most of these regions were also detected by the CSS or FSS methods.
      CONCLUSIONS: Overall, we recommend using the methods BYM and MLE for cluster
      detection with the similar population and structure of regions as in Manitoba.
      The potential clusters of bowel disorders are generally located in the southern
      part of the province including the eastern part of the city of Winnipeg. These
      results may represent real increases in bowel disorders or they may be an
      indication of other covariates that were not adjusted for in the model used here.
      Further investigation is needed to examine these findings, and also to explore
      the cause of these increases.

PMID- 24673851
TI  - Demographic and clinical characteristics of young people seeking help at youth
      mental health services: baseline findings of the Transitions Study.
AB  - AIM: The Transitions Study was designed to establish a cohort of young people (12
      25 years) seeking help for mental health problems, in order to longitudinally
      explore and refine a clinical staging model of the development and progression of
      mental disorders. This paper presents the baseline demographic and clinical
      characteristics of the cohort, particularly the nature and severity of
      psychopathology. METHOD: All eligible young people attending one of four
      headspace clinical services were invited to participate, and completed a battery
      of self-report and interviewer-administered measures of psychopathology and
      functional impairment at baseline, which will be repeated at the annual follow
      up. RESULTS: Of 1615 eligible clients, 802 young people (66% women; mean age =
      18.3 years) consented to participate and completed baseline assessments
      (participation rate = 50%). The severity of mental health problems varied, with
      51% meeting the criteria for probable caseness related to generalized anxiety,
      45% presenting with moderate to severe depressive symptoms and over a third
      experiencing subthreshold psychotic symptomatology. Disordered eating (32%) and
      problematic tobacco (56%), cannabis (30%) and alcohol (38%) use also affected a
      significant proportion. Overall, 39% of the cohort were classed as being
      functionally impaired at baseline. CONCLUSION: The Transitions Study recruited a
      heterogeneous cohort at baseline in relation to the nature and severity of mental
      health problems and levels of functional impairment. The variation in clinical
      presentations within the cohort, from mild, through moderate to severe levels of
      psychopathology and impairment, increases the likelihood of the Transitions Study
      ultimately being able to achieve its aims of empirically testing a clinical
      staging model for mental disorders.

PMID- 24673852
TI  - To settle or to move? The interplay between two classes of cyclic lipopeptides in
      the biocontrol strain Pseudomonas CMR12a.
AB  - Pseudomonas CMR12a is a biocontrol strain that produces phenazine antibiotics and
      as yet uncharacterized cyclic lipopeptides (CLPs). The CLPs of CMR12a were
      studied by chemical structure analysis and in silico analysis of the gene
      clusters encoding the non-ribosomal peptide synthetases responsible for CLP
      biosynthesis. CMR12a produces two different classes of CLPs: orfamides B, D and
      E, whereby the latter two represent new derivatives of the orfamide family, and
      sessilins A-C. The orfamides are made up of a 10 amino acid peptide coupled to a
      beta-hydroxydodecanoyl or beta-hydroxytetradecanoyl fatty acid moiety, and are
      related to orfamides produced by biocontrol strain Pseudomonas protegens Pf-5.
      The sessilins consist of an 18-amino acid peptide linked to a beta
      hydroxyoctanoyl fatty acid and differ in one amino acid from tolaasins, toxins
      produced by the mushroom pathogen Pseudomonas tolaasii. CLP biosynthesis mutants
      were constructed and tested for biofilm formation and swarming motility.
      Orfamides appeared indispensable for swarming while sessilin mutants showed
      reduced biofilm formation, but enhanced swarming motility. The interplay between
      the two classes of CLPs fine tunes these processes. The presence of sessilins in
      wild type CMR12a interferes with swarming by hampering the release of orfamides
      and by co-precipitating orfamides to form a white line in agar.

PMID- 24673854
TI  - Peptide formation by N-methyl amino acids in translation is hastened by higher pH
      and tRNA(Pro).
AB  - Applications of N-methyl amino acids (NMAAs) in drug discovery are limited by
      their low efficiencies of ribosomal incorporation, and little is known
      mechanistically about the steps leading to incorporation. Here, we demonstrate
      that a synthetic tRNA body based on a natural N-alkyl amino acid carrier,
      tRNA(Pro), increases translation incorporation rates of all three studied NMAAs
      compared with tRNA(Phe)- and tRNA(Ala)-based bodies. We also investigate the pH
      dependence of the incorporation rates and find that the rates increase
      dramatically in the range of pH 7 to 8.5 with the titration of a single proton.
      Results support a rate-limiting peptidyl transfer step dependent on deprotonation
      of the N-nucleophile of the NMAA. Competition experiments demonstrate that
      several futile cycles of delivery and rejection of A-site NMAA-tRNA are required
      per peptide bond formed and that increasing magnesium ion concentration increases
      incorporation yield. Data clarify the mechanism of ribosomal NMAA incorporation
      and provide three generalizable ways to improve incorporation of NMAAs in
      translation.

PMID- 24673853
TI  - PSMD9 expression predicts radiotherapy response in breast cancer.
AB  - BACKGROUND: More than 50% of cancer patients are recommended to receive
      radiotherapy. Recommendations are based mainly on clinical and pathological
      factors and not intrinsic tumour radio-sensitivity. Use of radiotherapy according
      to predictive markers would potentially reduce costly over-treatment, and improve
      the treatment risk-benefit ratio and cancer outcomes. Tumour expression of the
      26S proteasome has been reported to predict radiotherapy response: low expression
      was associated with higher rates of local recurrence after radiotherapy,
      suggesting that low proteasome expression and activity was associated with radio
      resistance. However, this conclusion is at odds with the emerging use of
      proteasome inhibitors as radio-sensitizers. Our aim was to further analyse the
      relevance of 26S proteasome expression, focussing specifically on the PSMD9
      subunit, in the largest clinical cohort to date, and to investigate the
      functional role of PSMD9 in radio-sensitivity in breast cancer cell lines.
      METHODS: We examined expression of PSMD9 using immunohistochemistry in a cohort
      of 157 breast cancer patients, including 32 cases (20.4%) that subsequently
      developed local recurrences. The value of expression as a prognostic or
      radiotherapy predictive marker was tested using Kaplan-Meier and Cox regression
      analyses. PSMD9 function was examined in breast cancer cell lines MCF7 and MDA-MB
      231 using siRNA knock-downs and colony forming assays after irradiation. RESULTS:
      Low tumour PSMD9 expression was significantly associated with a reduced incidence
      of local recurrence in patients receiving adjuvant radiotherapy (univariate log
      rank p = 0.02; multivariate regression p = 0.009), but not in those treated
      without radiotherapy, suggesting that low PSMD9 expression was associated with
      relative tumour radio-sensitivity. In support of this, reduction of PSMD9
      expression using siRNA in breast cancer cell lines in vitro sensitized cells to
      radiotherapy. CONCLUSIONS: We conclude that PSMD9 expression may predict
      radiotherapy benefit, with low expression indicative of relative radio
      sensitivity, the opposite of previous reports relating to 26S proteasome
      expression. Our conclusion is compatible with use of proteasome inhibitors as
      radio-sensitizers, and highlights PSMD9 as a potential target for radio
      sensitizing drugs.

PMID- 24673855
TI  - Elevated IL-6 levels in patients with atypical depression but not in patients
      with typical depression.
AB  - Elevated levels of the proinflammatory cytokine Interleukin-6 (IL-6) are among
      the most consistent findings in patients with major depressive disorder (MDD).
      Additionally, some evidence suggests that elevated cytokine levels in patients
      with major depression are responsible for the development of metabolic syndrome
      in patients suffering from MDD. Therefore, the aim of the study was to examine
      the concentrations of IL-6 in specific subtypes of MDD and to investigate their
      relationship to metabolic factors. Twenty-four patients with typical (24) and
      atypical (eight) major depression according to DSM-IV criteria were studied and
      compared to 24 normal controls. Blood samples were collected during a stepwise
      glucose-clamp procedure, and IL-6 concentrations were measured by high
      sensitivity ELISA. IL-6 levels were elevated in patients suffering from atypical
      depression but not in patients with typical depression, compared to normal
      controls. IL-6 correlated significantly with HbA1c, insulin, waist girth, BMI,
      number of alcoholic drinks per week and C-reactive protein. Our data indicate
      that high concentrations of IL-6 during the glucose clamp may be limited to the
      atypical subgroup of patients with MDD. 

PMID- 24673857
TI  - Successful treatment of transient osteoporosis with intravenous zoledronate: a
      case report.

PMID- 24673856
TI  - Prophage-like elements present in Mycobacterium genomes.
AB  - BACKGROUND: Prophages, integral components of many bacterial genomes, play
      significant roles in cognate host bacteria, such as virulence, toxin biosynthesis
      and secretion, fitness cost, genomic variations, and evolution. Many prophages
      and prophage-like elements present in sequenced bacterial genomes, such as
      Bifidobacteria, Lactococcus and Streptococcus, have been described. However,
      information for the prophage of Mycobacterium remains poorly defined. RESULTS: In
      this study, based on the search of the complete genome database from GenBank, the
      Whole Genome Shotgun (WGS) databases, and some published literatures, thirty
      three prophages were described in detail. Eleven of them were full-length
      prophages, and others were prophage-like elements. Eleven prophages were firstly
      revealed. They were phiMAV_1, phiMAV_2, phiMmcs_1, phiMmcs_2, phiMkms_1,
      phiMkms_2, phiBN42_1, phiBN44_1, phiMCAN_1, phiMycsm_1, and phiW7S_1. Their
      genomes and gene contents were firstly analyzed. Furthermore, comparative
      genomics analyses among mycobacterioprophages showed that full-length prophage
      phi172_2 belonged to mycobacteriophage Cluster A and the phiMmcs_1, phiMkms_1,
      phiBN44_1, and phiMCAN_1 shared high homology and could be classified into one
      group. CONCLUSIONS: To our knowledge, this is the first systematic
      characterization of mycobacterioprophages, their genomic organization and
      phylogeny. This information will afford more understanding of the biology of
      Mycobacterium.

PMID- 24673859
TI  - Predicting risk of seclusion and restraint in a psychiatric intensive care (PIC)
      unit.

PMID- 24673858
TI  - Cardiopulmonary effects of an infusion of remifentanil or morphine in horses
      anesthetized with isoflurane and dexmedetomidine.
AB  - OBJECTIVE: To examine the cardiopulmonary effects of infusions of remifentanil or
      morphine, and their influence on recovery of horses anesthetized with isoflurane
      and dexmedetomidine. STUDY DESIGN: Randomized crossover study with 7-day rest
      periods. ANIMALS: Six adult horses (507 +/- 61 kg). METHODS: After the horses
      were sedated with xylazine, anaesthesia was induced with ketamine and diazepam,
      and maintained with isoflurane. After approximately 60 minutes, a dexmedetomidine
      infusion was started (0.25 MUg kg(-1) then 1.0 MUg(-1) kg(-1) hour(-1) ) in
      combination with either saline (group S), morphine (0.15 mg kg(-1) then 0.1 mg
      kg(-1) hour(-1) ; group M), or remifentanil (6.0 MUg kg(-1) hour(-1) ; group R)
      for 60 minutes. Mean arterial pressure, heart rate, end-tidal carbon dioxide
      tension, and end-tidal isoflurane concentration were recorded every 5 minutes.
      Core body temperature, cardiac output, right ventricular and arterial blood-gas
      values were measured every 15 minutes. Cardiac index, systemic vascular
      resistance (SVR), intrapulmonary shunt fraction, alveolar dead space, oxygen
      delivery and extraction ratio were calculated. Recoveries were videotaped and
      scored by two observers blinded to the treatment. Data were analyzed using
      repeated measures anova followed by Dunnett's or Bonferroni's significant
      difference test. Recovery scores were analyzed using a Kruskal-Wallis test.
      RESULTS: No significant differences were found among groups. Compared to
      baseline, heart rate decreased and SVR increased significantly in all groups, and
      cardiac index significantly decreased in groups S and M. Hemoglobin
      concentration, oxygen content and oxygen delivery significantly decreased in all
      groups. The oxygen extraction ratio significantly increased in groups M and R.
      Lactate concentration significantly increased in group S. Recovery scores were
      similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine alone
      or in combination with remifentanil or morphine infusions was infused for 60
      minutes without adverse effects in the 6 healthy isoflurane-anesthetized horses
      in this study.

PMID- 24673860
TI  - Mandatory oral glucose tolerance tests identify more diabetics in stable patients
      with chronic heart failure: a prospective observational study.
AB  - BACKGROUND: Many patients with chronic heart failure (CHF) are believed to have
      unrecognized diabetes, which is associated with a worse prognosis. This study
      aimed to describe glucose tolerance in a general stable CHF population and to
      identify determinants of glucose tolerance focusing on body composition and
      skeletal muscle strength. METHODS: A prospective observational study was set up.
      Inclusion criteria were diagnosis of CHF, stable condition and absence of glucose
      lowering medication. Patients underwent a 2 h oral glucose tolerance test (OGTT),
      isometric strength testing of the upper leg and dual energy x-ray absorptiometry.
      Health-related quality of life and physical activity level were assessed by
      questionnaire. RESULTS: Data of 56 participants were analyzed. Despite near
      normal fasting glucose values, 55% was classified as prediabetic, 14% as
      diabetic, and 20% as normal glucose tolerant. Of all newly diagnosed diabetic
      patients, 79% were diagnosed because of 2 h glucose values only and none because
      of HbA1c. Univariate mixed model analysis revealed ischaemic aetiology, daily
      physical activity, E/E', fat trunk/fat limbs and extension strength as possible
      explanatory variables for the glucose curve during the glucose tolerance test.
      When combined in one model, only fat trunk/fat limbs and E/E' remained
      significant predictors. Furthermore, fasting insulin was correlated with fat
      mass/height2 (r = 0.51, p < 0.0001), extension strength (r = -0.33, p < 0.01) and
      triglycerides (r = 0.39, p < 0.01). CONCLUSIONS: Our data confirm that a large
      majority of CHF patients have impaired glucose tolerance. This glucose
      intolerance is related to fat distribution and left ventricular end-diastolic
      pressure.

PMID- 24673861
TI  - [Not Available].

PMID- 24673862
TI  - The challenge of maximizing safety in radiation oncology.
AB  - There is a growing interest in the evolving nature of safety challenges in
      radiation oncology. Understandably, there has been a great deal of focus on the
      mechanical and computer aspects of new high-technology treatments (eg, intensity
      modulated radiation therapy). However, safety concerns are not limited to dose
      calculations and data transfer associated with advanced technologies. They also
      stem from fundamental changes in our workflow (eg, multiple hand-offs), the
      relative loss of some traditional "end of the line" quality assurance tools (port
      films and light fields), condensed fractionation schedules, and an under
      appreciation for the physical limitations of new techniques. Furthermore, changes
      in our workspace and tools (eg, electronic records, planning systems), and
      workloads (eg, billing, insurance, regulations) may have unforeseen effects on
      safety. Safety initiatives need to acknowledge the multiple factors affecting
      risk. Our current challenges will not be adequately addressed simply by defining
      new policies and procedures. Rather, we need to understand the frequency and
      causes of errors better, particularly those that are most likely to cause harm.
      Then we can incorporate principles into our workspace that minimize these risks
      (eg, automation, standardization, checklists, redundancy, and consideration of
      "human factors" in the design of products and workspaces). Opportunities to
      enhance safety involve providing support through diligent examinations of
      staffing, schedules, communications, teamwork, and work environments. We need to
      develop a culture of safety in which all team members are alerted to the
      possibility of harm, and they all work together to maximize safety. The goal is
      not to eliminate every error. Rather, we should focus our attention on conditions
      (eg, rushing) that can cause real patient harm, and/or those conditions that
      reflect systemic problems that might lead to errors more likely to cause harm.
      Ongoing changes in clinical practice mandate continued vigilance to minimize the
      risks of error, combined with new, nontraditional approaches to create a safer
      patient environment. 

PMID- 24673863
TI  - Improving safety in radiation oncology.

PMID- 24673864
TI  - Improving patient safety in radiation oncology.
AB  - Beginning in the 1990s, and emphasized in 2000 with the release of an Institute
      of Medicine report, health care providers and institutions have dedicated time
      and resources to reducing errors that impact the safety and well-being of
      patients. However, in January 2010, the first of a series of articles appeared in
      The New York Times that described errors in radiation oncology that grievously
      impacted patients. In response, the American Association of Physicists in
      Medicine and the American Society for Radiation Oncology sponsored a working
      meeting entitled "Safety in Radiation Therapy: A Call to Action." The meeting
      attracted 400 attendees, including medical physicists, radiation oncologists,
      medical dosimetrists, radiation therapists, hospital administrators, regulators,
      and representatives of equipment manufacturers. The meeting was co-hosted by 14
      organizations in the United States and Canada. The meeting yielded 20
      recommendations that provided a pathway to reducing errors and improving patient
      safety in radiation therapy facilities everywhere. 

PMID- 24673865
TI  - Implications of previously undetected incidental findings on 3D CT simulation
      scans for radiation therapy.
AB  - PURPOSE: To determine the frequency of significant incidental findings on
      diagnostic quality simulation computed tomographic (CT) scans for radiotherapy
      planning. METHODS AND MATERIALS: An institutional review board--approved
      retrospective review of radiation simulation CT scans with diagnostic radiology
      reports, performed between 2004 and 2006, was conducted to identify incidental
      findings, defined as previously unreported findings. An incidental finding was
      classified as a cancer-related finding (CRF) if it could potentially change the
      staging and treatment of the cancer. Other nonmalignant findings, not likely
      caused by cancer, were classified as noncancer findings (NCFs). RESULTS: Of the
      580 CT scans performed for radiation planning, 61 (11%) NCFs and 45 (8%) CRFs
      were identified. Common NCFs included degenerative bone changes (20%),
      diverticulosis (15%), and lung (11%), kidney (10%), thyroid (10%), and vascular
      (7%) abnormalities. Two of the vascular NCFs were thrombi requiring
      anticoagulation. The CRFs included suspected local recurrence (22%);
      lymphadenopathy (18%); significant progression of local disease (16%); distant
      metastasis to the liver (16%), bone (11%), and other sites (16%); and malignancy
      not evident (2%). Eight CRFs prompted additional workup, all with negative
      results, causing 2 treatment delays. Three CRFs warranted change of treatment
      without further imaging, including the use of induction chemotherapy before
      radiation, an increase in radiation dose, and proceeding with surgery up front
      followed by radiation. The remaining 34 CRFs did not require additional action
      because the abnormalities were already addressed by the planned treatment (33%),
      were believed to be benign with further review (29%), or would have been better
      evaluated by additional imaging that had been scheduled prior to radiation
      simulation (13%). Overall, 7 of 580 (1%) scans prompted treatment alterations,
      including 2 treatment delays. CONCLUSION: A comprehensive review of radiation
      planning CT scans by diagnostic radiologists resulted in a significant change in
      medical or cancer management in only a small percentage of cases.

PMID- 24673866
TI  - Revisiting unnecessary larynx irradiation with whole-neck IMRT.
AB  - PURPOSE: To determine if whole-neck intensity-modulated radiotherapy (IMRT)
      spares the larynx as well as techniques that match a conventional anterior-neck
      field to an IMRT plan superior to the larynx. METHODS AND MATERIALS: This is a
      dosimetric study using the treatment planning image sets from 5 consecutively
      treated patients with node-positive squamous cell carcinoma of the oropharynx,
      all with gross disease above the larynx. We compared 3 techniques for irradiating
      the mid- and low-neck lymphatics: whole-neck IMRT, conventional anterior-neck
      field with split-beam matching, and conventional anterior-neck field with
      gradient matching. Prescription doses for the high-, intermediate-, and standard
      risk planning target volumes were 70 Gy, 60 Gy, and 50 Gy, respectively. RESULTS:
      The mean larynx dose was similar with all techniques with median values: whole
      neck IMRT, 28 Gy (range, 17-30 Gy); conventional field with split-beam matching,
      26 Gy (range, 21-33 Gy); conventional field with gradient matching, 30 Gy (range,
      25-31 Gy). CONCLUSIONS: With meticulous attention to the details of contouring
      and treatment planning, it is possible to use whole-neck IMRT without increasing
      the risk of larynx dysfunction compared to techniques that block the larynx in a
      conventional anterior-neck field. We discuss the potential advantages of each
      technique in this article.

PMID- 24673867
TI  - The development of oncology treatment guidelines: an analysis of the National
      Guidelines Clearinghouse.
AB  - PURPOSE: In the last 2 decades, guidelines have been developed to improve quality
      of patient care. A recent editorial of guideline development procedures suggested
      the process has significant limitations that affect their scientific validity.(1)
      This prompted us to review oncology treatment guidelines to determine if such
      limitations are widespread. METHODS AND MATERIALS: We performed a review of
      oncology treatment guidelines registered at the National Guidelines Clearinghouse
      (www.guideline.gov). Each guideline was independently reviewed by 2 authors and
      the following criteria were assessed: coordinating organization, guideline panel
      composition, reporting conflict of interest, peer review, dissent, expiration
      date, PubMed citation, and evidence-based scoring and grading of recommendations.
      Disagreements were resolved by consensus in subsequent discussions. RESULTS:
      Sixty-four guidelines were reviewed (39 [61%] were developed by a medical
      specialty society and 25 [39%] were developed by government agencies). Fifty
      (78%) guideline panels were multidisciplinary and 44 (69%) included individuals
      with epidemiologic and health services research expertise. Potential conflicts of
      interest were disclosed in 43 (67%) guidelines. Sixty (94%) guidelines underwent
      peer review, with external review in 31 (48%). Seventeen (27%) guidelines are
      indexed by PubMed. Fifty-one (80%) guidelines included evidence-based
      methodologies and 46 (72%) used evidence-based scoring of recommendations.
      Significant differences were observed according to coordinating organization (eg,
      disclosure of conflict of interest in 46% of guidelines developed by medical
      specialty societies versus 100% authored by government agencies [P <.0001]).
      CONCLUSIONS: The majority of oncology-related treatment guidelines registered at
      the National Guidelines Clearinghouse satisfy most of the criteria for sound
      guideline development. Significant differences in these criteria were observed
      according to the coordinating organization that developed the guideline.

PMID- 24673868
TI  - Stereotactic ablative radiotherapy: what's in a name?

PMID- 24673869
TI  - Successful treatment of radiation-induced optic neuropathy.
AB  - Radiation-induced optic neuropathy is a rare but devastating side effect after
      radiation treatment. The treatment options for radiation-induced optic neuropathy
      have been limited and largely unsuccessful. A review of the literature was
      conducted to summarize the rationale and possible benefits of various treatments
      for radiation-induced optic neuropathy. 

PMID- 24673870
TI  - American Board of Radiology subspecialty certification in hospice and palliative
      medicine.

PMID- 24673871
TI  - First use of electromagnetic setup and real-time tracking in a pediatric patient
      with vaginal rhabdomyosarcoma.
AB  - We report the first use of the Calypso system (Calypso Medical, Seattle, WA) in a
      pediatric patient with group III vaginal rhabdomyosarcoma. The Calypso system was
      used to improve patient setup, to limit anesthesia, to provide for real-time
      tracking of target location, and to minimize the need for daily portal imaging
      studies and their associated extraneous radiation dose. 

PMID- 24673872
TI  - Preoperative radiation therapy for an extremity hemangiopericytoma: a case
      report.

PMID- 24673873
TI  - Adenoid cystic carcinoma of the lung: Response to tamoxifen after chemoradiation.
AB  - Primary adenoid cystic carcinoma of the lung is a rare subtype of lung cancer
      with a prolonged natural history but is difficult to completely resect surgically
      due to its proximal location. Hence radiotherapy plays a role for local control
      of these cancers. The role of systemic therapies in the treatment of adenoid
      cystic carcinoma of the lung remains unclear. Isolated case reports have
      previously described the treatment of primary adenoid cystic carcinoma of the
      lung with tamoxifen, resulting in partial control. We report the first case of
      primary adenoid cystic carcinoma of the lung treated with primary
      chemoradiotherapy due to unresectable location of the tumor, and disease
      stabilization with symptomatic response to tamoxifen following tumor recurrence.
      There is a need for further studies to investigate the role of anti-hormonal
      therapies in the treatment of adenoid cystic carcinoma of the lung.

PMID- 24673874
TI  - Cytochrome P4503A activity affects the gender difference in the development of
      steroid-induced osteonecrosis in rabbits.
AB  - The aim of this study was to investigate cytochrome P4503A activity and its
      correlation with the development of osternecrosis (ON) among male and female
      steroid-treated rabbits. Forty adult rabbits (male, n = 20; female, n = 20) were
      injected once with 20 mg/kg of methylprednisolone intramuscularly.
      Haematologically, cytochrome P4503A activity was measured by plasma 1'
      hydroxymidazolam-to-midazolam (1'-OH-MDZ/MDZ) ratio just before and 48 h after
      the steroid injection. We also measured the levels of oestradiol every week. Both
      femora and humeri were histopathologically examined for the presence of ON.
      Fifteen of 20 male rabbits (75%) developed ON, while 6 of 20 female rabbits (30%)
      did so. There was a significant difference in the rate of incidence of ON between
      male and female rabbits (P = 0.010). The 1'-OH-MDZ/MDZ ratio in female rabbits
      just before, as well as 48 h after the steroid injection was significantly higher
      than that in male rabbits (P = 0.039 and P = 0.001 respectively). In addition, 1'
      OH-MDZ/MDZ ratio in female rabbits significantly increased in 48 h after the
      steroid injection (P = 0.044), while that in male rabbits did not so (P = 0.978).
      The levels of oestradiol in female rabbits were significantly higher than those
      in male rabbits during the experimental period (P = 0.008). In conclusion, this
      study indicates that the gender difference in cytochrome P4503A activity may be
      one of the important factors for the development of steroid-induced ON, possibly
      due to the effects of oestradiol. 

PMID- 24673875
TI  - Influence of Vertical Soft Tissue Thickness on Crestal Bone Changes Around
      Implants with Platform Switching: A Comparative Clinical Study.
AB  - BACKGROUND: Numerous studies have shown the superiority of platform-switched
      implants in preserving crestal bone as compared with platform-matched implants.
      However, the influence of initial soft tissue thickness on development of crestal
      bone loss has not been addressed in previous studies; thus, further research is
      needed. PURPOSE: To evaluate crestal bone levels around platform-switched
      implants placed in thin and thick mucosal tissue. MATERIALS AND METHODS: Eighty
      patients (38 male and 42 female, mean age 44 +/- 3.34 years) received 80 bone
      level implants of 4.1 mm in diameter with platform switching (Institut Straumann
      AG, Basel, Switzerland). Tissue thickness was measured, and cases were
      distributed to Group 1, with thin soft tissue (2 mm or less, n = 40), and Group
      2, with thick tissue (more than 2 mm, n = 40). Implants were placed with a one
      stage approach and restored with screw-retained restorations. Radiographic
      examination was performed after implant placement, 2 months after healing, after
      restoration, and at 1-year follow-up post-reconstruction. Crestal bone loss was
      calculated. The Mann-Whitney U-test was applied, and significance was set to p <=
      .05. RESULTS: Implants in Group 1 (thin tissue) showed 0.79 mm of bone loss after
      2 months. After 1-year follow-up, bone loss was 1.17 mm. Implants in Group 2
      (thick tissue) showed bone loss of 0.17 mm after 2 months of implant placement
      and 0.21 mm after 1-year follow-up. The differences between groups were
      significant (p < .001) at both time points. CONCLUSIONS: It can be concluded that
      platform switching does not prevent crestal bone loss if, at the time of implant
      placement, mucosal tissue is thin. In thick soft tissue, use of platform-switched
      implants maintained crestal bone level with minimal remodeling.

PMID- 24673876
TI  - The effect of sleep on item recognition and source memory recollection among
      shift-workers and permanent day-workers.
AB  - We studied the effect of sleep versus wakefulness on item recognition and source
      memory recollection in a sample of shift-workers and permanent day-workers.
      Recognition of words that were previously viewed arrayed in quadrants of a page,
      and recollection of the original source location of the words on the page were
      assessed after a 12-h retention interval that was filled with wakefulness
      incorporating the subjects' work-shift, or an equal period that included sleep.
      Both shift-workers and permanent day-workers had poorer item recognition and
      source memory recollection when the retention interval was spent awake rather
      than including sleep. Shift-workers expressed larger deficits in performance than
      day-workers after wakefulness. This effect was not mediated by whether the shift
      workers were on a day- or night-shift at the time of the study. These results
      indicate that sleep is an important contributor to successful item recognition
      and source recollection, and that mnemonic processing in shift-workers may be
      especially sensitive across their work-shift.

PMID- 24673877
TI  - Students' attitudes toward and knowledge about snakes in the semiarid region of
      Northeastern Brazil.
AB  - BACKGROUND: Humans in various cultures have feared snakes, provoking an aversion
      and persecution that hinders conservation efforts for these reptiles. Such fact
      suggests that conservation strategies for snakes should consider the interactions
      and perceptions of the local population towards these animals. The aim of this
      study was to investigate students' perception of snakes and if attitudes and
      knowledge may differ according to gender and local residence (urban or rural).
      METHODS: Data was collected in the second half of 2012 and consisted of
      questionnaires applied to 108 students in the Basic Education School in the
      municipality of Sume, located in the semiarid region of Northeastern Brazil.
      RESULTS: The male respondents recognized more species than female did. Part of
      the students affirmed to have a fear of snakes, especially women. Nearly half of
      respondents (49%) showed negative behaviour towards these animals, reflecting the
      influence of potential risk and myths associated with snakes, and supported by a
      limited knowledge about these animals and their ecological and utilitarian role.
      We find that the rural students recognized significantly more species than the
      urban students. CONCLUSIONS: Our results point to the need for educational
      interventions in order to increase knowledge about the positive aspects
      associated with snakes, seeking to minimize the influence of myths and beliefs
      that contribute to a strong aversion to snakes by the locals. Conservation
      strategies should therefore engage students but also teachers, who are key
      individuals in the process.

PMID- 24673879
TI  - Effect of alcohol use on the course of bipolar disorder: one-year follow-up study
      using the daily prospective Life Chart method.
AB  - OBJECTIVES: Relatively little is known about the temporal relationship between
      alcohol use and subsequent mood changes in patients with bipolar disorder, and
      the available findings are inconsistent. The present study was a fine-grained
      analysis of the temporal relationship between alcohol use and short-term mood
      switching probabilities. METHODS: The study included 137 patients with bipolar
      disorder who performed daily self-ratings of their mood symptoms and the number
      of alcohol units consumed for a period of up to 52 weeks by using the National
      Institute of Mental Health self-rated prospective Life Chart Method. At baseline,
      the Structured Clinical Interview for DSM-IV was administered and demographic,
      social, and clinical characteristics were obtained. Multi-state models were used
      to assess the impact of the number of alcoholic drinks on patients' transition
      through different states of mood (depression, euthymia, and mania). RESULTS: The
      effect of alcohol use on the change in mood states was limited. For women in a
      depressive state, higher alcohol use was associated with a shorter time before
      entering the euthymic state [hazard ratio (HR) = 1.18, 95% confidence interval
      (CI): 1.03-1.36, p < 0.05], whereas, for men in an euthymic state, higher alcohol
      use was associated with a longer time before entering a manic state (HR = 0.81,
      95% CI: 0.71-0.92, p < 0.05). The correlation between the consumed number of
      drinks per week and the average mood severity score of the following week was 
      0.01 (p < 0.001), indicating that only 0.01% of the variance in mood severity in
      this population is explained by alcohol use. Possible explanations for these
      findings are discussed. CONCLUSIONS: The current study, using a fine-grained
      analysis, suggests that alcohol use does not have a direct effect on the course
      of bipolar disorder in patients using mood stabilizers.

PMID- 24673878
TI  - Development of new PCR primers by comparative genomics for the detection of
      Helicobacter suis in gastric biopsy specimens.
AB  - BACKGROUND: Although the infection rate of Helicobacter suis is significantly
      lower than that of Helicobacter pylori, the H. suis infection is associated with
      a high rate of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In
      addition, in vitro cultivation of H. suis remains difficult, and some H. suis
      infected patients show negative results on the urea breath test (UBT). MATERIALS
      AND METHODS: Female C57BL/6J mice were orally inoculated with mouse gastric
      mucosal homogenates containing H. suis strains TKY or SNTW101 isolated from a
      cynomolgus monkey or a patient suffering from nodular gastritis, respectively.
      The high-purity chromosomal DNA samples of H. suis strains TKY and SNTW101 were
      prepared from the infected mouse gastric mucosa. The SOLiD sequencing of two H.
      suis genomes enabled comparative genomics of 20 Helicobacter and 11 Campylobacter
      strains for the identification of the H. suis-specific nucleotide sequences.
      RESULTS: Oral inoculation with mouse gastric mucosal homogenates containing H.
      suis strains TKY and SNTW101 induced gastric MALT lymphoma and the formation of
      gastric lymphoid follicles, respectively, in C57BL/6J mice. Two conserved
      nucleotide sequences among six H. suis strains were identified and were used to
      design diagnostic PCR primers for the detection of H. suis. CONCLUSIONS: There
      was a strong association between the H. suis infection and gastric diseases in
      the C57BL/6 mouse model. PCR diagnosis using an H. suis-specific primer pair is a
      valuable method for detecting H. suis in gastric biopsy specimens.

PMID- 24673880
TI  - Comparison of two surgical techniques for carotid endarterectomy: conventional
      and eversion.
AB  - BACKGROUND: The role of carotid endarterectomy for the treatment of
      atherosclerotic carotid bifurcation disease is now well established. The aim of
      this study was to compare durability, postoperative death, stroke, minor strokes,
      cranial nerve injuries, neck hematomas, myocardial infarctions, or surgical
      defects and restenosis at the operative site following short- and mid-term
      duration of the advantages eversion carotid endarterectomy (E-CEA) compared to
      conventional carotid endarterectomy (C-CEA). PATIENTS AND METHODS: Between March
      2003 and November 2012, primary CEAs were performed in 380 consecutive patients
      by the same surgical groups. These patients were evaluated retrospectively. C-CEA
      was performed in 202 patients, and E-CEA was performed in 178 patients. Carotid
      duplex ultrasonography was performed in all patients at 1, 6, 12 and 24 months
      after CEA to identify residual atherosclerotic carotid disease. RESULTS: Mean age
      was 67.3+/-13.4 years in the E-CEA group and 64.8+/-14.8 years in the C-CEA
      group. Mean cross-clamping time in the E-CEA group was 9.54+/-2.6 minutes and
      12.62+/-2.7 minutes for C-CEA group (P=0.236). Three postoperative strokes
      occurred (one after E-CEA and two after C-CEA). In the E-CEA group and C-CEA
      group respectively, carotid stenosis rates were found in 4 patients (2.24%) and
      in 5 (2.97%) at a follow-up period of 26 months. CONCLUSION: Classical
      endarterectomy still remains the gold standard surgical technique for patients
      who are selected for coronary artery disease surgery. Nevertheless, we believe
      that eversion endarterectomy, which has some advantages, must be kept in mind as
      an alternative approach.

PMID- 24673881
TI  - Ventromedial prefrontal cortex is critical for the regulation of amygdala
      activity in humans.
AB  - BACKGROUND: Dysfunction in the ventromedial prefrontal cortex (vmPFC) is believed
      to play a pivotal role in the pathogenesis of mood and anxiety disorders. Leading
      neurocircuitry models of these disorders propose that hypoactivity in the vmPFC
      engenders disinhibited activity of the amygdala and, consequently, pathologically
      elevated levels of negative affect. This model predicts that a selective loss or
      diminution of function of the vmPFC would result in heightened activity of the
      amygdala. Although this prediction has been borne out in rodent lesion and
      electrophysiologic studies using fear conditioning and extinction paradigms,
      there has not yet been a definitive test of this prediction in humans. METHODS:
      We tested this prediction through a novel use of functional magnetic resonance
      imaging in four neurosurgical patients with focal, bilateral vmPFC damage.
      RESULTS: Relative to neurologically healthy comparison subjects, the patients
      with vmPFC lesions exhibited potentiated amygdala responses to aversive images
      and elevated resting-state amygdala functional connectivity. No comparable group
      differences were observed for activity in other brain regions. CONCLUSIONS: These
      results provide unique evidence for the critical role of the vmPFC in regulating
      activity of the amygdala in humans and help elucidate the causal neural
      interactions that underlie mental illness.

PMID- 24673883
TI  - The fate of the fistula following renal transplantation.

PMID- 24673882
TI  - Genetic risk for attention-deficit/hyperactivity disorder contributes to
      neurodevelopmental traits in the general population.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the
      extreme end of traits in the general population. Epidemiological and twin studies
      suggest that ADHD frequently co-occurs with and shares genetic susceptibility
      with autism spectrum disorder (ASD) and ASD-related traits. The aims of this
      study were to determine whether a composite of common molecular genetic variants,
      previously found to be associated with clinically diagnosed ADHD, predicts ADHD
      and ASD-related traits in the general population. METHODS: Polygenic risk scores
      were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC)
      population sample (N = 8229) based on a discovery case-control genome-wide
      association study of childhood ADHD. Regression analyses were used to assess
      whether polygenic scores predicted ADHD traits and ASD-related measures
      (pragmatic language abilities and social cognition) in the ALSPAC sample.
      Polygenic scores were also compared in boys and girls endorsing any (rating >= 1)
      ADHD item (n = 3623). RESULTS: Polygenic risk for ADHD showed a positive
      association with ADHD traits (hyperactive-impulsive, p = .0039; inattentive, p =
      .037). Polygenic risk for ADHD was also negatively associated with pragmatic
      language abilities (p = .037) but not with social cognition (p = .43). In
      children with a rating >= 1 for ADHD traits, girls had a higher polygenic score
      than boys (p = .003). CONCLUSIONS: These findings provide molecular genetic
      evidence that risk alleles for the categorical disorder of ADHD influence
      hyperactive-impulsive and attentional traits in the general population. The
      results further suggest that common genetic variation that contributes to ADHD
      diagnosis may also influence ASD-related traits, which at their extreme are a
      characteristic feature of ASD.

PMID- 24673885
TI  - Mechanism of action of the SPARI vilazodone: serotonin 1A partial agonist and
      reuptake inhibitor.
AB  - ISSUE: Vilazodone is an antidepressant with a novel mechanism of pharmacologic
      action: serotonin partial agonist reuptake inhibitor (SPARI).

PMID- 24673886
TI  - 3-Hydroxybutyrate dehydrogenase-2 and ferritin-H synergistically regulate
      intracellular iron.
AB  - Siderophores are best known as small iron-binding molecules that facilitate iron
      uptake in bacteria and fungi. In our previous study, we demonstrated that
      eukaryotes also produce siderophore-like molecules via a remarkably conserved
      biosynthetic pathway. A member of the short-chain dehydrogenase family of
      reductases, 3-hydroxybutyrate dehydrogenase-2, catalyzes a rate-limiting step in
      the biogenesis of the mammalian siderophore. Physiologically, depletion of the
      mammalian siderophore by inhibiting expression of the 3-hydroxybutyrate
      dehydrogenase-2 gene (Bdh2) results in abnormal accumulation of intracellular
      iron, increased oxidative stress, and mitochondrial iron deficiency. Thus, the
      mammalian siderophore is an important regulator of cellular iron homeostasis. The
      cellular iron storage protein ferritin also regulates iron metabolism and
      protects cells from oxidative stress. Depletion of ferritin results in
      intracellular iron accumulation, predisposes to oxidative stress, and confers a
      growth advantage to cells. We therefore hypothesize that the siderophore and
      ferritin coregulate cellular iron metabolism/homeostasis in eukaryotes. We tested
      this prediction by depleting both the siderophore and ferritin. This resulted in
      a marked accumulation of cellular iron, and caused increased sensitivity to
      oxidants. Interestingly, cells lacking both the siderophore and ferritin
      proliferated at a higher rate than cells lacking either of these components
      alone. Taken together, our findings suggest that the siderophore and ferritin
      synergistically regulate cellular iron levels. 

PMID- 24673884
TI  - Incorporation of extracellular fatty acids by a fatty acid kinase-dependent
      pathway in Staphylococcus aureus.
AB  - Acyl-CoA and acyl-acyl carrier protein (ACP) synthetases activate exogenous fatty
      acids for incorporation into phospholipids in Gram-negative bacteria. However,
      Gram-positive bacteria utilize an acyltransferase pathway for the biogenesis of
      phosphatidic acid that begins with the acylation of sn-glycerol-3-phosphate by
      PlsY using an acyl-phosphate (acyl-PO4 ) intermediate. PlsX generates acyl-PO4
      from the acyl-ACP end-products of fatty acid synthesis. The plsX gene of
      Staphylococcus aureus was inactivated and the resulting strain was both a fatty
      acid auxotroph and required de novo fatty acid synthesis for growth. Exogenous
      fatty acids were only incorporated into the 1-position and endogenous acyl groups
      were channeled into the 2-position of the phospholipids in strain PDJ39
      (DeltaplsX). Extracellular fatty acids were not elongated. Removal of the
      exogenous fatty acid supplement led to the rapid accumulation of intracellular
      acyl-ACP and the abrupt cessation of fatty acid synthesis. Extracts from the
      DeltaplsX strain exhibited an ATP-dependent fatty acid kinase activity, and the
      acyl-PO4 was converted to acyl-ACP when purified PlsX is added. These data reveal
      the existence of a novel fatty acid kinase pathway for the incorporation of
      exogenous fatty acids into S. aureus phospholipids.

PMID- 24673887
TI  - The puzzle of Buruli ulcer transmission, ethno-ecological history and the end of
      "love" in the Akonolinga district, Cameroon.
AB  - The "One World One Health Initiative" has attended little to the priorities,
      concepts and practices of resource-poor communities confronting disease and the
      implications of these concerns for its biomedical, ecological and institutional
      approach to disease surveillance and control. Using the example of Buruli ulcer
      (BU) and its bacterial etiology, Mycobacterium ulcerans, in south-central
      Cameroon, we build on debates about the contributions of "local knowledge" and
      "alternative models" to biomedical knowledge of disease transmission. BU's mode
      of transmission remains poorly understood. Our approach employs ethno-ecological
      histories - local understandings of the putative emergence and expansion of a
      locally important, neglected disease. We develop these histories from 52
      individual and small group interviews, group discussions, and participant
      observation of daily and seasonal activities, conducted in 2013-2013. These
      histories offer important clues about past environmental and social change that
      should guide further ecological, epidemiological research. They highlight a key
      historical moment (the late 1980s and 1990s); specific ecological
      transformations; new cultivation practices in unexploited zones that potentially
      increased exposure to M. ulcerans; and ecological degradation that may have
      lowered nutritional standards and heightened susceptibility to BU. They also
      recast transmission, broadening insight into BU and its local analog, atom, by
      emphasizing the role of social change and economic crisis in its emergence and
      expansion. 

PMID- 24673888
TI  - Camel milk, amoxicillin, and a prayer: medical pluralism and medical humanitarian
      aid in the Somali Region of Ethiopia.
AB  - This paper details how exposure to new clinics, diagnostic technologies, and
      pharmaceuticals during humanitarian relief operations in the Somali Region of
      Ethiopia shaped local pluralistic health systems and altered the ways in which
      residents subsequently conceived of and treated illness and disease. Despite
      rising demand for pharmaceuticals and diagnostic technologies among Somalis in
      Ethiopia, local ethnophysiologies continued to draw upon popular ideas about
      humoral flows, divine action, and spirit possession. Demands for therapeutic
      camel milk, Qur'anic spiritual healing, herbal remedies, and other historically
      popular therapies persisted, but were shaped by concurrent demands for and
      understandings of diagnostic biotechnologies and pharmaceutical medications. The
      reverse was also true: contemporary understandings and uses of non-biomedical
      healing modalities among Somalis shaped evaluations of clinical care, including
      healthcare during humanitarian responses. To illustrate these phenomena, based on
      ethnographic research in eastern Ethiopia between 2007 and 2009, this paper
      explores three topics vital to Somalis' pluralistic healthcare systems: camel
      milk and the management of digestive bile; women's experiences and clinical
      presentations with pain and disorder in their reproductive systems; and the
      rising popularity of high-tech diagnostic tests. I conclude that medical
      humanitarian aid never happens in a vacuum or among truly treatment-naive
      populations. Instead, aid unfolds within ever-changing and pluralistic health
      cultures, and it permanently alters and is altered by the frames within which
      people evaluate and make future decisions about healthcare. 

PMID- 24673890
TI  - Modern contraceptive use among sexually active men in Uganda: does discussion
      with a health worker matter?
AB  - BACKGROUND: Family planning programs have recently undergone a fundamental shift
      from being focused on women only to focusing on men individually, or on both
      partners. However, contraceptive use among married men has remained low in most
      high-fertility countries including Uganda. Men's role in reproductive decision
      making remains an important and neglected part of understanding fertility control
      both in high-income and low-income countries. This study examines whether
      discussion of family planning with a health worker is a critical determinant of
      modern contraceptive use by sexually active men, and men's reporting of partner
      contraceptive use. METHODS: The study used data from the 2011 Uganda Demographic
      and Health Survey comprising 2,295 men aged 15-54 years. Specifically, analyses
      are based on 1755 men who were sexually active 12 months prior to the study.
      Descriptive statistics, Pearson's chi-square test, and logistic regression were
      used to identify factors that influenced modern contraceptive use among sexually
      active men in Uganda. RESULTS: Findings indicated that discussion of family
      planning with a health worker (OR=1.85; 95% CI: 1.29-2.66), region (OR=0.41; 95%
      CI: 0.21-0.77), education (OR=2.13; 95% CI: 1.01-4.47), wealth index: richer
      (OR=2.52; 95% CI: 1.58-4.01), richest (OR=2.47; 95% CI: 1.44-4.22), surviving
      children (OR=2.04; 95% CI:1.16-3.59) and fertility preference (OR=3.50; 95% CI:
      1.28-9.61) were most significantly associated with modern contraceptive use among
      men. CONCLUSIONS: The centrality of the role of discussion with health workers in
      predicting men's participation in family planning matters may necessitate
      creation of opportunities for their further engagement at health facilities as
      well as community levels. Men's discussion of family planning with health workers
      was significantly associated with modern contraceptive use. Thus, creating
      opportunities through which men interact with health workers, for instance during
      consultations, may improve contraceptive use among couples.

PMID- 24673889
TI  - Siblings, friends, course-mates, club-mates: how adolescent health behavior
      homophily varies by race, class, gender, and health status.
AB  - Many unhealthy behaviors develop during adolescence, and these behaviors can have
      fundamental consequences for health and mortality in adulthood. Social network
      structure and the degree of homophily in a network affect how health behaviors
      and innovations are spread. However, the degree of health behavior homophily
      across different social ties and within subpopulations is unknown. This paper
      addresses this gap in the literature by using a novel regression model to
      document the degree of homophily across various relationship types and
      subpopulations for behaviors of interest that are related to health outcomes.
      These patterns in health behavior homophily have implications for which behaviors
      and ties should be the subjects of future research and for predicting how
      homophily may shape health programs focused on specific subpopulations (gender,
      race, class, health status) or a specific social context (families, peer groups,
      classrooms, or school activities). 

PMID- 24673891
TI  - Early intervention in psychosis: a feasibility study financed by the Italian
      Center on Control of Maladies.
AB  - AIM: In November 2005 the Italian Center on Control of Maladies, a department
      operating under the Ministry of Health, financed a project aimed at evaluating
      the feasibility of a protocol of intervention based on the early intervention in
      psychosis (EIP) model within the Italian public mental health-care network.
      METHODS: The study was carried out between March 2007 and December 2009. It
      involved five centres operating under the Departments of Mental Health of Milan
      (Programma 2000), Rome (area D), Grosseto, Salerno (Nocera) and Catanzaro
      (Soverato). RESULTS: Enrolment lasted 12 months, at the end of which 43 patients
      were enrolled as first-episode psychosis (FEP), and 24 subjects as ultra high
      risk (UHR) patients. Both FEP and UHR samples included a preponderance of male
      patients. A family history of psychosis was rarely reported in both samples. The
      FEP incidence rate was lower than expected on the basis of international
      estimates of the incidence of schizophrenia but within the expected figure for
      the estimated Italian rates in three centres out of five. CONCLUSIONS: Overall,
      the study proved that an EIP centre can be established within the public
      Department of Mental Health to reach a good fraction of the cases in need of
      treatment. Since then, several studies have been set up to assess the feasibility
      of EIP in the Italian public mental health sector in Lombardy and Tuscany, and in
      2012 the Emilia-Romagna Regional Authority started an educational plan aimed at
      implementing the EIP model in all the Mental Health Departments in the region.

PMID- 24673892
TI  - Noncovalent spin labeling of riboswitch RNAs to obtain long-range structural NMR
      restraints.
AB  - Paramagnetic relaxation enhancement (PRE) NMR is a powerful method to study
      structure, dynamics and function of proteins. Up to now, the application of PRE
      NMR on RNAs is a significant challenge due to the limited size of chemically
      synthesized RNA. Here, we present a noncovalent spin labeling strategy to spin
      label RNAs in high yields required for NMR studies. The approach requires the
      presence of a helix segment composed of about 10 nucleotides (nt) but is not
      restricted by the size of the RNA. We show successful application of this
      strategy on the 2'dG sensing aptamer domain of Mesoplasma florum (78 nt). The
      aptamer domain was prepared in two fragments. A larger fragment was obtained by
      biochemical means, while a short spin labeled fragment was prepared by chemical
      solid-phase synthesis. The two fragments were annealed noncovalently by
      hybridization. We performed NMR, cw-EPR experiments and gel shift assays to
      investigate the stability of the two-fragment complex. NMR analysis in (15)N
      TROSY and (1)H,(1)H-NOESY spectra of both unmodified and spin labeled aptamer
      domain show that the fragmented system forms a stable hybridization product, is
      in structural agreement with the full length aptamer domain and maintains its
      function. Together with structure modeling, experimentally determined (1)H-Gamma2
      rates are in agreement with reported crystal structure data and show that
      distance restraints up to 25 A can be obtained from NMR PRE data of RNA.

PMID- 24673893
TI  - Indole negatively impacts predation by Bdellovibrio bacteriovorus and its release
      from the bdelloplast.
AB  - Bdellovibrio bacteriovorus is a predatory bacterium that attacks a wide range of
      Gram-negative bacterial pathogens and is proposed to be a potential living
      antibiotic. In this study, we evaluated the effects of indole, a bacterial
      signalling molecule commonly produced within the gut, on the predatory ability of
      B. bacteriovorus HD100. Indole significantly delayed predation on Escherichia
      coli MG1655 and Salmonella enterica KACC 11595 at physiological concentrations
      (0.25 to 1 mM) and completely inhibited predation when present at 2 mM.
      Microscopic analysis revealed that indole blocked the predator from attacking the
      prey. Furthermore, indole was not toxic to the predator but slowed down its
      motility. Microarray and reverse transcription quantitative polymerase chain
      reaction (RT-qPCR) analyses confirmed that as the gene group showing the greatest
      downregulation in the presence of indole was flagellar assembly genes. Indole
      also caused a wide spectrum changes in gene expression including general
      downregulation of genes involved in ribosome assembly. Furthermore, indole
      addition to the predatory culture after the entrance of B. bacteriovorus into the
      prey periplasm slowed down bdelloplast lysis. In conclusion, indole can have
      significant impacts on the predation efficiency, which should be taken into
      consideration especially if B. bacteriovorus is to be applied as a probiotic or
      living antibiotic. 

PMID- 24673894
TI  - Short-term intake of a Japanese-style healthy lunch menu contributes to
      prevention and/or improvement in metabolic syndrome among middle-aged men: a non
      randomized controlled trial.
AB  - BACKGROUND: Metabolic syndrome is now widely appreciated as a cluster of
      metabolic abnormalities such as visceral obesity, hypertension, hyperglycemia and
      dyslipidemia. To date, incidence of metabolic syndrome is continuously increasing
      worldwide.In addition, low vegetable consumption has recently become a serious
      issue in Japan. Furthermore, Japan is facing a shortfall in places offering food
      that can help prevent metabolic syndrome in the first place. Our study is
      designed to influence these developments. We conducted a non-randomized
      controlled trial by offering a Japanese-style healthy lunch menu to middle-aged
      men in a workplace cafeteria. This menu was designed to prevent and reduce
      metabolic syndrome. METHODS: This intervention study took the form of a non
      randomized controlled trial. Participants chose the control or intervention
      group. The control group consumed their habitual lunches without restriction and
      only nutrient contents were assessed. The intervention group received a Japanese
      style healthy lunch at a workplace cafeteria for 3 months. The participants
      worked in offices at a city hall and mostly had low levels of physical activity.
      Data of 35 males (control group: 7 males, intervention group: 28 males, mean age:
      47.2 +/- 7.9 years) were collected and analyzed. RESULTS: We obtained an
      effective outcome by demonstrating that ongoing intake of a Japanese-style
      healthy lunch decreased blood pressure and serum lipids and increased plasma
      ghrelin levels. The results grew more pronounced as intake of Japanese-style
      healthy lunches increased in frequency. CONCLUSIONS: This study presents new
      empirical data as a result of an original intervention program undertaken in
      Japan. A Japanese-style healthy lunch menu containing many vegetables consumed
      can help prevent and/or improve metabolic syndrome.

PMID- 24673896
TI  - Breakdown in REM sleep circuitry underlies REM sleep behavior disorder.
AB  - During rapid eye movement (REM) sleep, skeletal muscles are almost paralyzed.
      However, in REM sleep behavior disorder (RBD), which is a rare neurological
      condition, muscle atonia is lost, leaving afflicted individuals free to enact
      their dreams. Although this may sound innocuous, it is not, given that patients
      with RBD often injure themselves or their bed-partner. A major concern in RBD is
      that it precedes, in 80% of cases, development of synucleinopathies, such as
      Parkinson's disease (PD). This link suggests that neurodegenerative processes
      initially target the circuits controlling REM sleep. Clinical and basic
      neuroscience evidence indicates that RBD results from breakdown of the network
      underlying REM sleep atonia. This finding is important because it opens new
      avenues for treating RBD and understanding its link to neurodegenerative
      disorders. 

PMID- 24673895
TI  - Human serum inhibits adhesion and biofilm formation in Candida albicans.
AB  - BACKGROUND: Candida albicans can form biofilms on intravenous catheters; this
      process plays a key role in the pathogenesis of catheter infections. This study
      evaluated the effect of human serum (HS) on C. albicans biofilm formation and the
      expression of adhesion-related genes in vitro. A C. albicans laboratory strain
      (ATCC90028) and three clinical strains were grown for 24 h in RPMI 1640
      supplemented with HS or RPMI 1640 alone (as a control). The growth of biofilm
      cells of four strains was monitored by a Live Cell Movie Analyzer, and by XTT
      reduction assay. The expression of the adhesion-related genes BCR1, ALS1, ALS3,
      HWP1 and ECE1 was analyzed by RT-PCR at three time points (60 min, 90 min, and 24
      h). RESULTS: In the adhesion phase, C. albicans cells kept a Brownian movement in
      RPMI medium containing HS until a large number of germ tubes were formed. In the
      control group, C. albicans cells quickly adhered to the bottom of the reaction
      plate. Compared with RPMI 1640, medium supplemented with 3-50% HS caused a
      significant decrease in biofilm development (all p < 0.001). However, the
      presence of HS had no significant inhibitory effect on the pre-adhered biofilms
      (all p > 0.05). Biofilm formation was also inhibited by heat-inactivated and
      proteinase K pre-treated HS. The presence of 50% HS did not significantly affect
      the planktonic growth of C. albicans (p > 0.05). At three time points, HS
      inhibited expression of the ALS1 and ALS3 genes and promoted expression of the
      HWP1 and ECE1 genes. Significant up-regulation of BCR1 was observed only at the
      90-min point. CONCLUSIONS: Human serum reduces biofilm formation by inhibiting
      the adhesion of C. albicans cells. This response may be associated with the down
      regulation of adhesion-related genes ALS1, ALS3 and BCR1. The inhibitory serum
      component is protease-resistant and heat stable.

PMID- 24673898
TI  - Respiratory system compliance and resistance in canine anesthesia practice: do we
      have a reference?

PMID- 24673897
TI  - Consensus statement on the investigation and management of non-radiographic axial
      spondyloarthritis (nr-axSpA).
AB  - AIM: Non-radiographic axial spondyloarthritis (nr-axSpA) is axial inflammatory
      arthritis where plain radiographic damage is not evident. An unknown proportion
      of these patients will progress to ankylosing spondylitis (AS). The increasing
      recognition of nr-axSpA has been greatly assisted by the widespread use of
      magnetic resonance imaging. The aim of this article was to construct a set of
      consensus statements based on a literature review to guide investigation and
      promote best management of nr-axSpA. METHODS: A literature review using Medline
      was conducted covering the major investigation modalities and treatment options
      available. A group of rheumatologists and a radiologist with expertise in
      investigation and management of SpA reviewed the literature and formulated a set
      of consensus statements. The Grade system encompassing the level of evidence and
      strength of recommendation was used. The opinion of a patient with nr-axSpA and a
      nurse experienced in the care of SpA patients was also sought and included.
      RESULTS: The literature review found few studies specifically addressing nr
      axSpA, or if these patients were included, their results were often not
      separately reported. Fourteen consensus statements covering investigation and
      management of nr-axSpA were formulated. The level of agreement was high and
      ranged from 8.1 to 9.8. Treatment recommendations vary little with established
      AS, but this is primarily due to the lack of available evidence on the specific
      treatment of nr-axSpA. CONCLUSION: The consensus statements aim to improve the
      diagnosis and management of nr-axSpA. We aim to raise awareness of this condition
      by the public and doctors and promote appropriate investigation and management.

PMID- 24673899
TI  - Introduction to the special issue: nanomaterials-- toxicology and medical
      applications.

PMID- 24673900
TI  - Theranostic nanomedicine for cancer detection and treatment.
AB  - Cancer is the second leading cause of death in the USA according to the American
      Cancer Society. In the past 5 years, "theranostic nanomedicine", for both
      therapeutics and imaging, has shown to be "the right drug for the right patient
      at the right moment" to manage deadly cancers. This review article presents an
      overview of recent developments, mainly from the authors' laboratories, along
      with potential medical applications for theranostic nanomedicine including basic
      concepts and critical properties. Finally, we outline the future research
      direction and possible challenges for theranostic nanomedicine research.

PMID- 24673901
TI  - Cell microenvironment stimuli-responsive controlled-release delivery systems
      based on mesoporous silica nanoparticles.
AB  - To develop novel tumor cell microenvironment stimuli-responsive smart controlled
      release delivery systems is one of the current common interests of materials
      science and clinical medicine. Meanwhile, mesoporous silica nanoparticles as a
      promising drug carrier have become the new area of interest in the field of
      biomedical application in recent years because of their unique characteristics
      and abilities to efficiently and specifically entrap cargo molecules. This review
      describes the more recent developments and achievements of mesoporous silica
      nanoparticles in drug delivery. In particular, we focus on the stimuli-responsive
      controlled-release systems that are able to respond to tumor cell environmental
      changes, such as pH, glucose, adenosine-5'-triphosphate (ATP), glutathione (GSH),
      and H(2)O(2).

PMID- 24673902
TI  - Raman spectroscopy in the analysis of food and pharmaceutical nanomaterials.
AB  - Raman scattering is an inelastic phenomenon. Although its cross section is very
      small, recent advances in electronics, lasers, optics, and nanotechnology have
      made Raman spectroscopy suitable in many areas of application. The present
      article reviews the applications of Raman spectroscopy in food and drug analysis
      and inspection, including those associated with nanomaterials. Brief overviews of
      basic Raman scattering theory, instrumentation, and statistical data analysis are
      also given. With the advent of Raman enhancement mechanisms and the progress
      being made in metal nanomaterials and nanoscale metal surfaces fabrications,
      surface enhanced Raman scattering spectroscopy has become an extra sensitive
      method, which is applicable not only for analysis of foods and drugs, but also
      for intracellular and intercellular imaging. A Raman spectrometer coupled with a
      fiber optics probe has great potential in applications such as monitoring and
      quality control in industrial food processing, food safety in agricultural plant
      production, and convenient inspection of pharmaceutical products, even through
      different types of packing. A challenge for the routine application of surface
      enhanced Raman scattering for quantitative analysis is reproducibility. Success
      in this area can be approached with each or a combination of the following
      methods: (1) fabrication of nanostructurally regular and uniform substrates; (2)
      application of statistic data analysis; and (3) isotopic dilution. 

PMID- 24673903
TI  - Electron spin resonance spectroscopy for the study of nanomaterial-mediated
      generation of reactive oxygen species.
AB  - Many of the biological applications and effects of nanomaterials are attributed
      to their ability to facilitate the generation of reactive oxygen species (ROS).
      Electron spin resonance (ESR) spectroscopy is a direct and reliable method to
      identify and quantify free radicals in both chemical and biological environments.
      In this review, we discuss the use of ESR spectroscopy to study ROS generation
      mediated by nanomaterials, which have various applications in biological,
      chemical, and materials science. In addition to introducing the theory of ESR, we
      present some modifications of the method such as spin trapping and spin labeling,
      which ultimately aid in the detection of short-lived free radicals. The
      capability of metal nanoparticles in mediating ROS generation and the related
      mechanisms are also presented. 

PMID- 24673904
TI  - Mechanisms of nanotoxicity: generation of reactive oxygen species.
AB  - Nanotechnology is a rapidly developing field in the 21(st) century, and the
      commercial use of nanomaterials for novel applications is increasing
      exponentially. To date, the scientific basis for the cytotoxicity and
      genotoxicity of most manufactured nanomaterials are not understood. The
      mechanisms underlying the toxicity of nanomaterials have recently been studied
      intensively. An important mechanism of nanotoxicity is the generation of reactive
      oxygen species (ROS). Overproduction of ROS can induce oxidative stress,
      resulting in cells failing to maintain normal physiological redox-regulated
      functions. This in turn leads to DNA damage, unregulated cell signaling, change
      in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are
      critical determinants that can affect the generation of ROS. These critical
      determinants, discussed briefly here, include: size, shape, particle surface,
      surface positive charges, surface-containing groups, particle dissolution, metal
      ion release from nanometals and nanometal oxides, UV light activation,
      aggregation, mode of interaction with cells, inflammation, and pH of the medium. 

PMID- 24673905
TI  - Mechanistic characterization of titanium dioxide nanoparticle-induced toxicity
      using electron spin resonance.
AB  - Titanium dioxide nanoparticles (TiO(2) NPs) are one of the most widely used
      nanomaterials that have been manufactured worldwide and applied in different
      commercial realms. The well-recognized ability of TiO(2) to promote the formation
      of reactive oxygen species (ROS) has been extensively studied as one of the
      important mechanisms underlying TiO(2) NPs toxicity. As the "gold standard"
      method to quantify and identify ROS, electron spin resonance (ESR) spectroscopy
      has been employed in many studies aimed at evaluating TiO(2) NPs safety. This
      review aims to provide a thorough discussion of current studies using ESR as the
      primary method to unravel the mechanism of TiO(2) NPs toxicity. ESR spin label
      oximetry and immune-spin trapping techniques are also briefly introduced, because
      the combination of spin trapping/labeling techniques offers a promising tool for
      studying the oxidative damage caused by TiO(2) NPs.

PMID- 24673906
TI  - Reactive oxygen species-related activities of nano-iron metal and nano-iron
      oxides.
AB  - Nano-iron metal and nano-iron oxides are among the most widely used engineered
      and naturally occurring nanostructures, and the increasing incidence of
      biological exposure to these nanostructures has raised concerns about their
      biotoxicity. Reactive oxygen species (ROS)-induced oxidative stress is one of the
      most accepted toxic mechanisms and, in the past decades, considerable efforts
      have been made to investigate the ROS-related activities of iron nanostructures.
      In this review, we summarize activities of nano-iron metal and nano-iron oxides
      in ROS-related redox processes, addressing in detail the known homogeneous and
      heterogeneous redox mechanisms involved in these processes, intrinsic ROS-related
      properties of iron nanostructures (chemical composition, particle size, and
      crystalline phase), and ROS-related bio-microenvironmental factors, including
      physiological pH and buffers, biogenic reducing agents, and other organic
      substances. 

PMID- 24673907
TI  - Genotoxicity of titanium dioxide nanoparticles.
AB  - Titanium dioxide nanoparticles (TiO(2)-NPs, <100 nm) are increasingly being used
      in pharmaceuticals and cosmetics due to the unique properties derived from their
      small sizes. However, their large surface-area to mass ratio and high redox
      potential may negatively impact human health and the environment. TiO(2)-NPs can
      cause inflammation, pulmonary damage, fibrosis, and lung tumors and they are
      possibly carcinogenic to humans. Because cancer is a disease involving mutation,
      there are a large number of studies on the genotoxicity of TiO(2)-NPs. In this
      article, we review the results that have been reported in the literature, with a
      focus on data generated from the standard genotoxicity assays. The data include
      genotoxicity results from the Ames test, in vitro and in vivo Comet assay, in
      vitro and in vivo micronucleus assay, sister chromatid exchange assay, mammalian
      cell hypoxanthine-guanine phosphoribosyl transferase gene assay, the wing somatic
      mutation and recombination assay, and the mouse phosphatidylinositol glycan,
      class A gene assay. Inconsistent results have been found in these assays, with
      both positive and negative responses being reported. The in vitro systems for
      assessing the genotoxicity of TiO(2)-NPs have generated a greater number of
      positive results than the in vivo systems, and tests for DNA and chromosome
      damage have produced more positive results than the assays measuring gene
      mutation. Nearly all tests for measuring the mutagenicity of TiO(2)-NPs were
      negative. The current data indicate that the genotoxicity of TiO(2)-NPs is
      mediated mainly through the generation of oxidative stress in cells.

PMID- 24673908
TI  - Assessment of the toxic potential of graphene family nanomaterials.
AB  - Graphene, a single-atom-thick carbon nanosheet, has attracted great interest as a
      promising nanomaterial for a variety of bioapplications because of its
      extraordinary properties. However, the potential for widespread human exposure
      raises safety concerns about graphene and its derivatives, referred to as
      graphene-family nanomaterials. This review summarizes recent findings on the
      toxicological effects and the potential toxicity mechanisms of graphene-family
      nanomaterials in bacteria, mammalian cells, and animal models. Graphene, graphene
      oxide, and reduced graphene oxide elicit toxic effects both in vitro and in vivo,
      whereas surface modifications can significantly reduce their toxic interactions
      with living systems. Standardization of terminology and the fabrication methods
      of graphene-family nanomaterials are warranted for further investigations
      designed to decrease their adverse effects and explore their biomedical
      applications.

PMID- 24673910
TI  - Using a holistic approach to assess the impact of engineered nanomaterials
      inducing toxicity in aquatic systems.
AB  - In this report, we critically reviewed selected intrinsic physicochemical
      properties of engineered nanomaterials (ENMs) and their role in the interaction
      of the ENMs with the immediate surroundings in representative aquatic
      environments. The behavior of ENMs with respect to dynamic microenvironments at
      the nano-bio-eco interface level, and the resulting impact on their toxicity,
      fate, and exposure potential are elaborated. Based on this literature review, we
      conclude that a holistic approach is urgently needed to fulfill our knowledge gap
      regarding the safety of discharged ENMs. This comparative approach affords the
      capability to recognize and understand the potential hazards of ENMs and their
      toxicity mechanisms, and ultimately to establish a quantitative and reliable
      system to predict such outcomes. 

PMID- 24673911
TI  - Neurotoxicity of nanoscale materials.
AB  - Nanotechnology has been applied in consumer products and commercial applications,
      showing a significant impact on almost all industries and all areas of society.
      Significant evidence indicates that manufactured nanomaterials and combustion
      derived nanomaterials elicit toxicity in humans exposed to these nanomaterials.
      The interaction of the engineered nanomaterials with the nervous system has
      received much attention in the nanotoxicology field. In this review, the
      biological effects of metal, metal oxide, and carbon-based nanomaterials on the
      nervous system are discussed from both in vitro and in vivo studies. The
      translocation of the nanoparticles through the blood-brain barrier or nose to
      brain via the olfactory bulb route, oxidative stress, and inflammatory mechanisms
      of nanomaterials are also reviewed.

PMID- 24673912
TI  - An update to depression case management by practice nurses in primary care: a
      service evaluation.
AB  - ACCESSIBLE SUMMARY: There is a recognized need to enhance non-pharmaceutical
      interventions in a way that is more accessible to the primary care population.
      Collaborative care has been shown to have a positive impact upon depression
      symptoms and a core element of the collaborative care approach is the case
      manager. This paper is a service evaluation of a collaborative care intervention
      that uses primary care nurses as the depression case manager and is a follow-up
      to the service audit carried out by Ekers and Wilson. The results support the
      notion that primary care nurses are ideally placed for delivering care to
      depressed patients; especially in cases were a patient also has a comorbid long
      term medical condition. There is a recognized need to enhance non-pharmaceutical
      interventions for depression in the primary care. This service evaluation of
      collaborative care for depression by primary care practice nurses is an update of
      Ekers and Wilson (2008), reporting outcomes 5 years following initial training.
      From an initial 13 trained practice nurses, three provided anonymized data. Mean
      post-treatment Patient Health Questionnaire-9 (PHQ9) score was 8 [standard
      deviation (SD) 6.53, n = 185], indicating a mean positive change in depression
      symptom level of 8.9 [SD 7.01, 95% confidence interval (CI) 7.89-9.93, P <
      0.001]. Subgroup analysis for patients identified with a comorbid long-term
      conditions (LTC) mean post-treatment PHQ9 score was 9 (SD 7.72, n = 33),
      indicating a mean positive change in depression symptom level of 8.1 (SD 5.79,
      95% CI 6.04-10.41, P < 0.001). Nurses provided feedback on the intervention
      showing potential areas that would benefit from further detailed qualitative
      review. It was concluded that primary care practice nurses would be ideally
      placed to deliver collaborative care to depression patients with comorbid LTCs.

PMID- 24673909
TI  - Molecular toxicity mechanism of nanosilver.
AB  - Silver is an ancient antibiotic that has found many new uses due to its unique
      properties on the nanoscale. Due to its presence in many consumer products, the
      toxicity of nanosilver has become a hot topic. This review summarizes recent
      advances, particularly the molecular mechanism of nanosilver toxicity. The
      surface of nanosilver can easily be oxidized by O(2) and other molecules in the
      environmental and biological systems leading to the release of Ag(+), a known
      toxic ion. Therefore, nanosilver toxicity is closely related to the release of
      Ag(+). In fact, it is difficult to determine what portion of the toxicity is from
      the nano-form and what is from the ionic form. The surface oxidation rate is
      closely related to the nanosilver surface coating, coexisting molecules,
      especially thiol-containing compounds, lighting conditions, and the interaction
      of nanosilver with nucleic acids, lipid molecules, and proteins in a biological
      system. Nanosilver has been shown to penetrate the cell and become internalized.
      Thus, nanosilver often acts as a source of Ag(+) inside the cell. One of the main
      mechanisms of toxicity is that it causes oxidative stress through the generation
      of reactive oxygen species and causes damage to cellular components including DNA
      damage, activation of antioxidant enzymes, depletion of antioxidant molecules
      (e.g., glutathione), binding and disabling of proteins, and damage to the cell
      membrane. Several major questions remain to be answered: (1) the toxic
      contribution from the ionic form versus the nano-form; (2) key enzymes and
      signaling pathways responsible for the toxicity; and (3) effect of coexisting
      molecules on the toxicity and its relationship to surface coating.

PMID- 24673913
TI  - Effect of combination treatment of S-amlodipine with peroxisome proliferator
      activated receptor agonists on metabolic and cardiovascular parameters in Zucker
      fa/fa rats.
AB  - BACKGROUND: Type 2 diabetes is a complex metabolic disorder characterized by
      hyperglycemia, impaired glucose tolerance and insulin resistance associated with
      dyslipidemia and hypertension. The available drugs are not sufficiently
      efficacious in reducing cardiovascular risk and restoring normal glucose
      metabolism associated with type 2 diabetes as a mono- or a combination therapy.
      The present study examined the combined effects of an antihypertensive (S
      Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated
      receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk
      factors in aged diabetic and insulin-resistant Zucker fa/fa rats. METHODS:
      Following combination treatment for 14 days, blood pressure (BP), serum glucose,
      total cholesterol and triglycerides were measured. Aortic ring study was
      conducted to determine the effect of combination treatments on phenylephrine
      induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation. RESULTS:
      In combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose
      (115.1 +/- 6.6 vs. 81.7 +/- 4.2), BP (184.4 +/- 5.0 vs. 155.1 +/- 5.0), serum
      triglycerides (362.5 +/- 47.5 vs. 211.1 +/- 23.7) and glucose intolerance when
      compared with vehicle treated Zucker fa/fa rats. Similar results were observed
      with the combination of S-Amlodipine and Ragaglitazar (Triglycerides, 362.5 +/-
      47.5 vs. 252.34 +/- 27.86; BP, 184.4 +/- 5.0 vs. 159.0 +/- 8.0) except for serum
      glucose. ACh-induced vasorelaxation in aortic rings was also superior with both
      of the combinations compared to individual treatment. Furthermore, there was less
      body weight gain and food intake with S-Amlodipine and Pioglitazone combination
      in Zucker fa/fa rats. S-Amlodipine itself caused significant reduction in glucose
      (115.1 +/- 6.6 vs. 89.7 +/- 2.7) and BP (184.4 +/- 5.0 vs. 156.1 +/- 4.0) with
      improvement in insulin sensitivity observed through oral glucose tolerance test.
      CONCLUSIONS: The results suggest that a combination of PPAR agonists and S
      Amlodipine has partial benefits in improving the cardiovascular risk factors such
      as reduction in triglyceride levels, associated with chronic type 2 diabetes, and
      therefore may be utilized as an approach for addressing some of these devastating
      metabolic syndrome complications.

PMID- 24673914
TI  - Controversies in the management of gastrointestinal stromal tumors.
AB  - Major advances in the medical treatment of gastrointestinal tumors (GISTs) have
      improved survival for both patients with advanced disease and those diagnosed
      with high-risk primary tumors. The Consensus approaches to best practice
      management of gastrointestinal stromal tumors, published in this journal in 2008,
      provided guidance for the management of GIST to both clinicians and regulatory
      authorities. Since then, clinical trials have demonstrated the benefit of
      adjuvant imatinib in high-risk patients, and mature data from advanced GIST
      studies suggest that a small but significant proportion of patients with advanced
      disease can achieve long-term benefit with ongoing imatinib treatment. Other
      evolving management strategies include the controversial use of palliative or
      debulking surgery to improve outcomes in advanced GIST and the development of
      promising new multikinase inhibitors, such as regorafenib, which has established
      benefit in the third-line setting. This review provides an update of recent
      developments in GIST management and discusses new controversies that these
      advances have generated. 

PMID- 24673915
TI  - Herpes simplex virus inoculation in murine rete testis results in irreversible
      testicular damage.
AB  - This study aimed to establish the influence of herpes simplex virus (HSV) on
      testis morphology and germ cell development using a model of ascending urogenital
      HSV infection in mice. Adult C57BL/6J mice were inoculated with 100 plaque
      forming units of HSV1 in rete testis. Viral proteins and HSV DNA were detected
      from 3 days postinoculation (DPI), while capsids and virions could be visualized
      at 6 DPI. Infectious activity of HSV was revealed by rapid culture method in
      testes from 3 to 14 DPI, and virus DNA by PCR - from 3 to 100 DPI. Germ and
      Sertoli cells were infected during the early stages of the infection, whereas
      interstitial cells only occasionally contained the virus at 21 and 45 DPI.
      Microscopic analysis revealed severe degeneration of the germinal epithelium in
      the infected testes. By 21 DPI, testes became atrophic and most Sertoli cells
      were destroyed. No testicular regeneration and no spermatozoa in the epididymis
      were observed at 45 and 100 DPI. From 3 DPI, inflammatory cells accumulated in
      the interstitium between damaged tubules; a significant increase in the number of
      CD4(+), CD8(+) T lymphocytes and F4/80(+) cells was observed in the infected
      testes. This study shows that in the case of HSV retrograde ascent into
      seminiferous tubules, the acute viral infection results in irreversible atrophy
      of the germinal epithelium, orchitis and infertility. These results may be used
      to further study viral orchitis and the influence of HSV on spermatogenesis and
      male fertility.

PMID- 24673917
TI  - [Not Available].

PMID- 24673916
TI  - Travel to Brazil: analysis of data from the Boston Area Travel Medicine Network
      (BATMN) and relevance to travelers attending world cup and olympics.
AB  - We describe travelers who were evaluated pre-travel to Brazil from March 2008
      through July 2010 in the Boston area. Of 599 Brazil travelers, 71%, 58%, and 50%
      received vaccines for yellow fever (YF), typhoid, and hepatitis A, respectively.
      Fewer received influenza and hepatitis B vaccines (14%, 11%). A total of 60%
      traveled during Brazil's peak influenza season, and one fourth visited during
      peak dengue transmission. The 2014 World Cup and 2016 Olympics include events
      throughout Brazil. Travelers should seek pre-travel assessment including YF and
      malaria risk; travelers should be vaccinated against influenza, be up to date on
      other routine vaccines, and be prepared to protect themselves against mosquitoes.

PMID- 24673918
TI  - Implications of comparative effectiveness research for radiation oncology.
AB  - PURPOSE: The essence of comparative effectiveness research (CER) is to understand
      what health interventions work, for which patients, and under what conditions.
      The objective of this article is to introduce the relative strengths and
      weaknesses of several forms of evidence to illustrate the potential for CER
      evidence generation within radiation oncology. METHODS: We introduce the
      underlying concepts of effectiveness and efficacy. We describe the design of
      traditional explanatory randomized trials (RCTs). We introduce the rationale,
      strengths, and weaknesses of several alternative study designs for comparative
      effectiveness, including pragmatic clinical trials, adaptive trials, and
      observational (nonrandomized) studies. RESULTS: Explanatory RCTs are designed to
      assess the efficacy of an intervention while achieving a high degree of internal
      validity. Pragmatic clinical trials (PCTs) are prospective studies performed in
      typical, real-world clinical practice settings. The emphasis of PCTs is to
      maintain a degree of internal validity while also maximizing external validity.
      Adaptive trials can be modified at interim stages using existing or evolving
      evidence in the course of a trial, which may allow trials to maintain clinical
      relevance by studying current treatments. Observational data are becoming
      increasingly important, given substantial funding for clinical registries and
      greater availability of electronic medical records and claims databases, but need
      to address well-known limitations such as selection bias. CONCLUSION: With the
      rapid proliferation of new and evolving radiotherapy technologies, it is
      incumbent upon our field to invest in building the evidence base for radiotherapy
      CER and to actively participate in current initiatives for generating comparative
      evidence.

PMID- 24673919
TI  - The overthrow of the (evidence) hierarchy.

PMID- 24673920
TI  - Finding the answers we need: comparative effectiveness.

PMID- 24673921
TI  - Rectal and bladder deformation and displacement during preoperative radiotherapy
      for rectal cancer: Are current margin guidelines adequate for conformal therapy?
AB  - PURPOSE: To evaluate rectal motion and estimate an appropriate target volume for
      preoperative radiotherapy (RT) for rectal cancer. METHODS: Between January 2006
      and December 2009, 17 rectal cancer patients undergoing preoperative RT underwent
      39 cone-beam computed tomographic scans (CBCTs). CBCTs were fused to treatment
      planning CT scans by bony anatomy. The rectum and bladder were contoured on each
      scan. Margins of 2, 5, 10, and 15 mm were added to the rectum, and the volume and
      percent rectum on CBCT outside each of these margins were determined. The
      clinical target volume (CTV) was examined to determine the necessary margin
      beyond the posterior bladder edge to ensure coverage of the mesorectum at all
      time points. RESULTS: Median percentage rectum on CBCT outside the planning
      rectum was 7.77% (range, 0.19%-42.91%). Two patients had 1 or more CBCT with 1%
      or greater rectum outside a 1.5 cm margin. Five patients had 1 or more CBCT with
      1% or greater rectum outside a 1.0 cm margin. A CTV extending 1 cm into the
      posterior bladder edge (CTV1.0) was adequate at all time points for 79% of
      evaluable patients, and a CTV with a 1.5 cm anterior margin was adequate for 93%
      of patients. For 2 patients, the rectum extended outside the CTV1.0 on CBCT.
      CONCLUSIONS: With a limited number of CBCT scans, we found that the rectum tended
      to remain within 1.5 cm of the initial location on treatment planning CT.
      However, an anterior margin of 1.5 cm beyond the posterior bladder edge provides
      better coverage of the mesorectum than 1 cm for the initial CTV.

PMID- 24673922
TI  - Rectal cancer: a moving target?

PMID- 24673923
TI  - Automating RTOG-defined target volumes for postmastectomy radiation therapy.
AB  - PURPOSE: Consistency in defining and contouring target structures in radiation
      therapy (RT) is critical for highly conformal RT, for evaluating treatment plans,
      and for quality assurance in multi-institutional RT trials. The Radiation Therapy
      Oncology Group (RTOG) has published consensus guidelines for contouring targets
      for postmastectomy RT. To aid in contouring such structures, we evaluated the
      potential use of an automated contouring technique, known as deformable image
      registration-based breast segmentation (DEF-SEG). METHODS AND MATERIALS: The RTOG
      definitions were used to contour the chest wall (CW); levels I, II, and III
      axillary nodes (Ax1, Ax2, Ax3); supraclavicular (SCV) nodes; internal mammary
      (IM) nodes; and the heart. Left-sided and right-sided templates were created. The
      DEF-SEG was then used to generate auto-segmented contours from the appropriate
      template to computed tomographic scans of 20 test cases (10 left, 10 right). To
      assess the accuracy of this method, those contours were manually modified as
      necessary to match the RTOG definitions, and the extent of the overlap was
      compared. The dosimetric impact of the difference in contours was then evaluated
      by comparing dose-volume histograms for modified and unmodified contours.
      RESULTS: Mean volume-overlap ratios between the unmodified DEF-SEG-generated
      contours and modified contours were as follows: CW, 0.91; Ax1, 0.68; Ax2, 0.64;
      Ax3, 0.68; SCV node, 0.66; IM node, 0.32, and the heart, 0.93. Mean differences
      in volume receiving 45 Gy (V45) for the modified versus unmodified contours were
      as follows: CW, 2.1%; SCV node, 4.8%; Ax1, 5.1%; Ax2, 5.6%; Ax3, 3.0%; and IM
      node, 10.1%. Mean differences in V10 between the modified heart and the
      unmodified heart were 0.4% for right-sided treatment and 0.5% for left-sided
      treatment. CONCLUSIONS: The DEF-SEG can be helpful for delineating structures
      according to the RTOG consensus guidelines, particularly for the CW and the
      heart. No clinically significant dosimetric differences were found between the
      modified and unmodified contours. The DEF-SEG may be useful for evaluating
      treatment plans for postmastectomy RT in multi-institutional trials.

PMID- 24673924
TI  - Potential for dose escalation in the postprostatectomy setting with intensity
      modulated radiation therapy: a dosimetric study using EORTC consensus guidelines
      for target volume contours.
AB  - PURPOSE: Radiation therapy (RT) is delivered as adjuvant and salvage therapy
      after radical prostatectomy for prostate cancer. Interest in dose escalation in
      this setting may necessitate more advanced RT techniques, such as intensity
      modulation. This study was designed to compare intensity-modulated radiation
      therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) planning.
      METHODS: Twenty patients were identified who received post--radical prostatectomy
      RT with 4-field, 3DCRT plans to 68.4 Gy. Contours were revised to comply with the
      European Organization for Research and Treatment of Cancer consensus guidelines.
      The IMRT plans with 5 versus 9 coplanar fields were compared for 10 patients.
      Then the 9-field IMRT plans were compared to 3DCRT in all 20 patients.
      Differences in dose-volume histogram values were evaluated using 2-tailed paired
      t tests. Cone beam computed tomographic images were analyzed to evaluate rectum
      doses in the treatment position during the RT course. The IMRT plans to 72.0 Gy
      were compared to 3DCRT to 68.4 Gy to be able to consider potential use in dose
      escalation. RESULTS: The 9-field IMRT plans (vs 3DCRT) improved bladder mean dose
      and volume receiving 65 Gy or more (V65), as well as rectum mean dose (31.6 Gy vs
      36.1 Gy; P < .001), volume receiving 75% or more of the prescription dose (24.4%
      vs 31.0%; P < .001), and V65 (10.5% vs 20.0%; P < .001). Advantages of IMRT were
      at the cost of small increases in maximum point doses delivered to the bladder
      and rectum. Cone beam computed tomographic images (n = 132) were analyzed for 8
      patients; rectum mean dose and V65 were also improved by IMRT on these scans.
      IMRT allowed increasing dose to 72.0 Gy with similar bladder and rectum mean
      doses, V65, and V40 compared to 3DCRT to a total dose of 68.4 Gy. CONCLUSIONS:
      The IMRT improves dosimetric parameters for the rectum and bladder, which may
      allow dose escalation after radical prostatectomy. Future studies should
      determine whether these advantages translate into improved clinical outcomes for
      prostate cancer patients.

PMID- 24673925
TI  - Anatomic differences after robotic-assisted radical prostatectomy and open
      prostatectomy: implications for radiation field design.
AB  - PURPOSE: To investigate the anatomy of the pelvis following robotic-assisted
      radical prostatectomy (RARP) compared to the anatomy of the pelvis following open
      prostatectomy (OP), and to determine if postoperative radiation field design
      should take surgical approach into consideration. METHODS AND MATERIALS: This
      report is a retrospective review of the postoperative pelvic magnetic resonance
      imaging (MRI) scans for all OP patients (10) and all RARP patients (15) who
      presented consecutively to the radiation oncology clinic and subsequently
      underwent MRI scanning between January 2007 and December 2008. All patients who
      presented are included in the study. We measured 13 distinct anatomic distances,
      and we used t tests to examine mean differences in each of the parameters between
      RARP and OP and analysis of variance to examine mean differences controlling for
      length of follow-up MRI postsurgery (in days) and body mass index as covariates.
      RESULTS: Of the measurements, we found that the superior levator separation is
      statistically significantly greater in the post-RARP group than in the post-OP
      group (P < .01). Similarly, the post-RARP group had a greater mean resection
      defect measurement (P = .01) as measured by a larger width of the bladder
      infundibulum. This suggests that the size of trigonal musculature defect is more
      pronounced after RARP. The total urethral length was statistically significantly
      longer in the RARP group (P = .03). The vesicorectal distance was variable
      depending on the location along the rectal wall but trended toward larger
      separation in the post-RARP group (P = .05). CONCLUSIONS: The pelvic anatomy
      after RARP is considerably different from that after OP. The current standard
      field design for post-prostatectomy radiation is defined by the post-OP pelvis.
      Our data support that the clinical target volume borders be expanded posteriorly
      and laterally in men who have undergone RARP. As RARP continues to become a more
      widespread surgical option for the management of localized prostate cancer,
      radiation field design may need to be adjusted.

PMID- 24673926
TI  - A novel modified dynamic conformal arc technique for treatment of peripheral lung
      tumors using stereotactic body radiation therapy.
AB  - PURPOSE: To describe and compare a novel, modified dynamic conformal arc (MDCA)
      technique for lung stereotactic body radiation therapy with the standard
      noncoplanar beam (NCB) technique based on stereotactic body radiation therapy
      (SBRT) coverage, dose conformality, normal tissue constraints, and treatment
      time. MATERIALS AND METHODS: Twenty consecutive medically inoperable patients
      with early stage, peripheral, non-small cell lung cancer treated with SBRT using
      an NCB technique were re-planned with a novel MDCA technique. Treatment plans
      were compared based on Radiation Therapy Oncology Group (RTOG) 0236 criteria for
      planning treatment volume (PTV) coverage and normal tissue dose constraints, as
      well as high- and moderate-dose conformality. Treatment times necessary to
      deliver the NCB plans were compared with the times of a separate group of 12
      consecutive patients treated with the MDCA technique at our institution. RESULTS:
      The MDCA technique resulted in improved coverage of the cranial and caudal
      regions of the PTV and generated plans that were significantly more conformal by
      all high-dose criteria proposed by the RTOG protocol. In terms of moderate-dose
      criteria, MDCA plans had a significantly lower maximum dose (2 cm from the PTV),
      whereas the ratio of the 50% dose volume to the volume of the PTV was equivalent
      between the 2 techniques. All normal tissue dose constraints proposed in the RTOG
      0236 protocol were met by each plan, although the median lung V20 and mean lung
      dose were slightly higher in the MDCA plans, whereas the chest wall dose was
      slightly lower. A 42% reduction in treatment time was observed when patients
      treated with the NCB technique were compared with a separate cohort of 12
      patients treated with the MDCA technique (P < .0001). CONCLUSIONS: The new MDCA
      technique described in this study resulted in enhanced PTV coverage, improved
      high- and moderate-dose conformality, simplified treatment planning, and reduced
      treatment time compared with results using the standard NCB technique.

PMID- 24673928
TI  - [Not Available].

PMID- 24673927
TI  - Myeloid sarcoma of the upper extremity causing compartment syndrome: a case
      report.

PMID- 24673929
TI  - Erratum: Marks LB, Jackson M, Xie L, et al. The challenge of maximizing safety in
      radiation oncology. Practical Radiat Oncol. 2011;1:2-14.

PMID- 24673930
TI  - High-dose dietary zinc oxide mitigates infection with transmissible
      gastroenteritis virus in piglets.
AB  - BACKGROUND: Zinc (Zn) supplementation has been shown to reduce the incidence of
      diarrhea and to protect animals from intestinal diseases, but the mechanisms of
      this protective effect against virus infection in vivo have not yet been
      elucidated. Transmissible gastroenteritis virus (TGEV) causes diarrhea in piglets
      with an age-dependent decrease of severity. RESULTS: We used 60 weaned piglets
      that were divided into three groups to evaluate the effect of different Zn levels
      added to a conventional diet (50 mg Zn/kg diet, Znlow, control group). The other
      groups received the diet supplemented with ZnO at final concentrations of 150 mg
      Zn/kg diet (Znmed), or 2,500 mg/kg diet (Znhigh). Oral challenge infection with
      TGEV was performed when the pigs had been fed for 1 week with the respective
      diet. Half of the piglets of each group were sacrificed at day 1 and 18 after
      challenge infection. Fecal consistency was improved and body weights increased in
      the Znhigh group when compared to the other groups, but no direct effect of Zn
      concentrations in the diet on fecal TGEV shedding and mucosal immune responses
      was detectable. However, in the Znhigh group, we found a prevention of villus
      atrophy and decreased caspase-3-mediated apoptosis of jejunal epithelium.
      Furthermore, pigs receiving high Zn diet showed a down-regulation of interferon
      (IFN)-alpha, oligoadenylate synthetase (OAS), Zn transporter SLC39A4 (ZIP4), but
      up-regulation of metallothionein-1 (MT1), as well as the Zn transporters SLC30A1
      (ZnT1) and SLC30A5 (ZnT5). In addition, forskolin-induced chloride secretion and
      epithelial resistance were controlled at a physiological level in the Znhigh but
      not the other groups. Finally, in the Znhigh group, we documented an earlier and
      higher systemic TGEV-specific serum antibody response. CONCLUSIONS: These results
      suggest that high dietary Zn could provide enhanced protection in the intestinal
      tract and stimulate the systemic humoral immune response against TGEV infection.

PMID- 24673931
TI  - Identification of in vivo regulators of the Vibrio cholerae xds gene using a high
      throughput genetic selection.
AB  - Vibrio cholerae, the causative agent of cholera, remains a threat to public
      health in areas with inadequate sanitation. As a waterborne pathogen, V. cholerae
      moves between two dissimilar environments, aquatic reservoirs and the intestinal
      tract of humans. Accordingly, this pathogen undergoes adaptive shifts in gene
      expression throughout the different stages of its lifecycle. One particular gene,
      xds, encodes a secreted exonuclease that was previously identified as being
      induced during infection. Here we sought to identify regulators responsible for
      the in vivo-specific induction of xds. A transcriptional fusion of xds to two
      consecutive antibiotic resistance genes was used to select transposon mutants
      that had inserted within or adjacent to regulatory genes and thereby caused
      increased expression of the xds fusion under non-inducing conditions. Large pools
      of selected insertion sites were sequenced in a high throughput manner using Tn
      seq to identify potential mechanisms of xds regulation. Our selection identified
      the two-component system PhoB/R as the dominant activator of xds expression. In
      vitro validation confirmed that PhoB, a protein which is only active during
      phosphate limitation, was responsible for xds activation. Using xds expression as
      a biosensor of the extracellular phosphate level, we observed that the mouse
      small intestine is a phosphate-limited environment. 

PMID- 24673932
TI  - Acceleration of Bone Regeneration by BMP-2-Loaded Collagenated Biphasic Calcium
      Phosphate in Rabbit Sinus.
AB  - PURPOSE: The objective of this study was to determine the effectiveness of
      collagenated biphasic calcium phosphate (CBCP) as a carrier for bone
      morphogenetic protein-2 (BMP-2) at the early stage of healing in rabbit sinus.
      MATERIAL AND METHODS: In 16 rabbits, BMP-2-loaded CBCP was grafted into one sinus
      (the BMP group) and saline-soaked CBCP was grafted into another sinus (the CTL
      group). The groups were assigned randomly. After 2 weeks (n = 8) or 4 weeks (n =
      8), radiographic and histological analysis was performed. RESULTS: Total
      augmented volume was significantly larger in the BMP group at both healing
      periods. Furthermore, new bone volume was significantly greater in the BMP group
      at 4 weeks. Marked bone formation near the schneiderian membrane was found in the
      BMP groups at the early healing period. At 4 weeks, evenly distributed new bone
      was observed in the BMP group, whereas the new bone was sparsely distributed in
      the central portion in the CTL group. CONCLUSION: It can be concluded that the
      addition of BMP-2 to CBCP resulted in a greater initial augmented volume as a
      result of postoperative swelling, which is replaced by early bone formation, and
      it was prominent near the Schneiderian membrane.

PMID- 24673933
TI  - A biophysical analysis of mitochondrial movement: differences between transport
      in neuronal cell bodies versus processes.
AB  - There is an increasing interest in factors that can impede cargo transport by
      molecular motors inside the cell. Although potentially relevant (Yi JY, Ori
      McKenney KM, McKenney RJ, Vershinin M, Gross SP, Vallee RB. High-resolution
      imaging reveals indirect coordination of opposite motors and a role for LIS1 in
      high-load axonal transport. J Cell Biol 2011;195:193-201), the importance of
      cargo size and subcellular location has received relatively little attention.
      Here we address these questions taking advantage of the fact that mitochondria -
      a common cargo - in Drosophila neurons exhibit a wide distribution of sizes. In
      addition, the mitochondria can be genetically marked with green fluorescent
      protein (GFP) making it possible to visualize and compare their movement in the
      cell bodies and in the processes of living cells. Using total internal reflection
      microscopy coupled with particle tracking and analysis, we quantified the
      transport properties of GFP-positive mitochondria as a function of their size and
      location. In neuronal cell bodies, we find little evidence for significant
      opposition to motion, consistent with a previous study on lipid droplets
      (Shubeita GT, Tran SL, Xu J, Vershinin M, Cermelli S, Cotton SL, Welte MA, Gross
      SP. Consequences of motor copy number on the intracellular transport of kinesin-1
      driven lipid droplets. Cell 2008;135:1098-1107). However, in the processes, we
      observe an inverse relationship between the mitochondrial size and velocity and
      the run distances. This can be ameliorated via hypotonic treatment to increase
      process size, suggesting that motor-mediated movement is impeded in this more
      confined environment. Interestingly, we also observe local mitochondrial
      accumulations in processes but not in cell bodies. Such accumulations do not
      completely block the transport but do increase the probability of mitochondria
      mitochondria interactions. They are thus particularly interesting in relation to
      mitochondrial exchange of elements. 

PMID- 24673935
TI  - Functional coexistence of twin arsenic resistance systems in Pseudomonas putida
      KT2440.
AB  - The genome of the soil bacterium Pseudomonas putida KT2440 bears two virtually
      identical arsRBCH operons putatively encoding resistance to inorganic arsenic
      species. Single and double chromosomal deletions in each of these ars clusters of
      this bacterium were tested for arsenic sensitivity and found that the
      contribution of each operon to the resistance to the metalloid was not additive,
      as either cluster sufficed to endow cells with high-level resistance. However,
      otherwise identical traits linked to each of the ars sites diverged when
      temperature was decreased. Growth of the various mutants at 15 degrees C (instead
      of the standard 30 degrees C for P. putida) uncovered that ars2 affords a much
      higher resistance to As (III) than the ars1 counterpart. Reverse transcription
      polymerase chain reaction of arsB1 and arsB2 genes as well as lacZ fusions to the
      Pars1 and Pars2 promoters traced the difference to variations in transcription of
      the corresponding gene sets at each temperature. Functional redundancy may thus
      be selected as a stable condition - rather than just as transient state - if it
      affords one key activity to be expressed under a wider range of physicochemical
      settings. This seems to provide a straightforward solution to regulatory problems
      in environmental bacteria that thrive under changing scenarios. 

PMID- 24673934
TI  - A large-scale, rapid public health response to rabies in an organ recipient and
      the previously undiagnosed organ donor.
AB  - This article describes and contrasts the public health response to two human
      rabies cases: one organ recipient diagnosed within days of symptom onset and the
      transplant donor who was diagnosed 18 months post-symptom onset. In response to
      an organ-transplant-related rabies case diagnosed in 2013, organ donor and
      recipient investigations were conducted by multiple public health agencies.
      Persons with potential exposure to infectious patient materials were assessed for
      rabies virus exposure. An exposure investigation was conducted to determine the
      source of the organ donor's infection. Over 100 persons from more than 20
      agencies spent over 2700 h conducting contact investigations in healthcare,
      military and community settings. The 564 persons assessed include 417 healthcare
      workers [5.8% recommended for post-exposure prophylaxis (PEP)], 96 community
      contacts (15.6% recommended for PEP), 30 autopsy personnel (50% recommended for
      PEP), and 21 other persons (4.8% recommended for PEP). Donor contacts represented
      188 assessed with 20.2% recommended for PEP, compared with 5.6% of 306 recipient
      contacts recommended for PEP. Human rabies cases result in substantial use of
      public health and medical resources, especially when diagnosis is delayed.
      Although rare, clinicians should consider rabies in cases of encephalitis of
      unexplained aetiology, particularly for cases that may result in organ donation.

PMID- 24673937
TI  - ["V" axillary incision for the management of tumors of upper outer quadrant and
      axillary tail of the breast: retrospective study and technical description].
AB  - INTRODUCTION: Tumors of the upper outer quadrant of the breast represent the most
      common location of breast malignant tumors. Although the choice of surgical
      approach should be dictated primarily by an imperative of oncological safety,
      esthetic and practical considerations of the surgeon as well as the esthetic
      demands of patients have become increasingly important with the development of
      breast conservative surgery. MATERIALS AND METHODS: In this retrospective study,
      we reviewed 30 patients (mean age: 62.3 years) who were operated for a tumor of
      the upper outer quadrant (50 %) or the axillary tail (50 %) of the breast and who
      received a "V" axillary incision between 2008 and 2012. The incision draws a "V"
      that comprises a horizontal incision in an axilla fold associated with a vertical
      arcuate incision in a Langer line of the breast. The number and type of
      postoperative complications were collected. Patients were asked about the quality
      of their scar, position of the areola and breast shape was notified during
      consultations control. RESULTS: The mean follow-up of patients was 32.7 months.
      No postoperative complications were observed. A percentage of 86.6 % of patients
      rated their scar result as excellent. We found no areolar malposition and no
      morphological deformation of the breast. The surgeons who performed this
      technique were very pleased with the wide exposure and the uniqueness of this
      incision fully respecting the architecture of the breast. CONCLUSION: "V"
      axillary incision is a useful and easily reproducible technical option for the
      management of tumors of the upper outer quadrant and the axillary tail of the
      breast.

PMID- 24673936
TI  - Identification and characterization of nuclear genes involved in photosynthesis
      in Populus.
AB  - BACKGROUND: The gap between the real and potential photosynthetic rate under
      field conditions suggests that photosynthesis could potentially be improved.
      Nuclear genes provide possible targets for improving photosynthetic efficiency.
      Hence, genome-wide identification and characterization of the nuclear genes
      affecting photosynthetic traits in woody plants would provide key insights on
      genetic regulation of photosynthesis and identify candidate processes for
      improvement of photosynthesis. RESULTS: Using microarray and bulked segregant
      analysis strategies, we identified differentially expressed nuclear genes for
      photosynthesis traits in a segregating population of poplar. We identified 515
      differentially expressed genes in this population (FC >= 2 or FC <= 0.5, P <
      0.05), 163 up-regulated and 352 down-regulated. Real-time PCR expression analysis
      confirmed the microarray data. Singular Enrichment Analysis identified 48
      significantly enriched GO terms for molecular functions (28), biological
      processes (18) and cell components (2). Furthermore, we selected six candidate
      genes for functional examination by a single-marker association approach, which
      demonstrated that 20 SNPs in five candidate genes significantly associated with
      photosynthetic traits, and the phenotypic variance explained by each SNP ranged
      from 2.3% to 12.6%. This revealed that regulation of photosynthesis by the
      nuclear genome mainly involves transport, metabolism and response to stimulus
      functions. CONCLUSIONS: This study provides new genome-scale strategies for the
      discovery of potential candidate genes affecting photosynthesis in Populus, and
      for identification of the functions of genes involved in regulation of
      photosynthesis. This work also suggests that improving photosynthetic efficiency
      under field conditions will require the consideration of multiple factors, such
      as stress responses.

PMID- 24673938
TI  - L-Asp is a useful tool in the purification of the ionotropic glutamate receptor
      A2 ligand-binding domain.
AB  - In purification of the ionotropic glutamate receptor A2 (GluA2) ligand-binding
      domain (LBD), L-Glu-supplemented buffers have previously been used for protein
      stabilization during the procedure. This sometimes hampers structural studies of
      low-affinity ligands, because L-Glu is difficult to displace, despite extensive
      dialysis. Here, we show that L-Asp binds to full-length GluA2 with low affinity
      (Ki = 0.63 mM) and to the GluA2 LBD with even lower affinity (Ki = 2.6 mM), and
      we use differential scanning fluorimetry to show that L-Asp is able to stabilize
      the isolated GluA2 LBD. We also show that L-Asp can replace L-Glu during
      purification, providing both equal yields and purity of the resulting protein
      sample. Furthermore, we solved three structures of the GluA2 LBD in the presence
      of 7.5, 50 and 250 mM L-Asp. Surprisingly, with 7.5 mM L-Asp, the GluA2 LBD
      crystallized as a mixed dimer, with L-Glu being present in one subunit, and
      neither L-Asp nor L-Glu being present in the other subunit. Thus, residual L-Glu
      is retained from the expression medium. On the other hand, only L-Asp was found
      at the binding site when 50 or 250 mM L-Asp was used for crystallization. The
      binding mode observed for L-Asp at the GluA2 LBD is very similar to that
      described for L-Glu. Taking our findings together, we have shown that L-Asp can
      be used instead of L-Glu for ligand-dependent stabilization of the GluA2 LBD
      during purification. This will enable structural studies of low-affinity ligands
      for lead optimization in structure-based drug design. DATABASE: Structural data
      are available in the Protein Data Bank under accession numbers 4O3B (7.5 mM L
      Asp), 4O3C (50 mM L-Asp), and 4O3A (250 mM L-Asp).

PMID- 24673939
TI  - Mothers impose physical activity restrictions on their asthmatic children and
      adolescents: an analytical cross-sectional study.
AB  - BACKGROUND: Physical activities are important for children and adolescents,
      especially asthmatics. A significant proportion is considered less active than
      their non-asthmatic peers and mother's beliefs about asthma are thought to be a
      determinant factor.The research objectives were to investigate whether mothers
      try to impose limitations on the physical activity (PA) of their asthmatic
      children/adolescents; identify associated factors; and explore if this attitude
      has any impact on children's PA levels. METHODS: In this cross sectional
      investigation, we studied 115 asthmatics aged between 9 and 19 years and their
      mothers. Asthma severity, PA level and exercise induced bronchospasm (EIB) were
      evaluated. Mothers were questioned on their beliefs about physical activity in
      non-asthmatic and asthmatic children, if they imposed restrictions on their
      children's physical activity, on EIB perception and personal levels of anxiety
      and depression. RESULTS: Ninety six percent of the mothers answered that PA are
      important for children and adolescents. Despite this, 37% of them admitted
      imposing restrictions to their children's PA. This attitude was associated with
      mother's negative opinions about asthmatics doing PA, perception of children's
      dyspnea after running on a treadmill, mother's anxiety level and children's
      asthma severity. The mother's restrictive attitudes were not associated with
      children's lower PA levels. CONCLUSION: A high proportion of the mothers said
      that they restrained their asthmatic children from engaging in physical activity.
      This fact should be recognized by health professionals and discussed with parents
      and caregivers as these negative beliefs may lead to conflicts and prejudiced
      attitudes that could discourage children's involvement in physical activities and
      sports.

PMID- 24673940
TI  - Preoperative and perioperative predictors of reactive and persistent depression
      after cardiac surgery: a three-month follow-up study.
AB  - BACKGROUND: Depression is commonly reported in patients after cardiac surgery and
      increases the risk of postoperative cardiac morbidity or mortality or both.
      Although preoperative depression has been implicated as the strongest predictor
      of depression after surgery, the characteristics thought to influence reactive or
      persistent depression have been poorly investigated in cardiac surgery patients.
      OBJECTIVE: Therefore, the main aim of this study was to examine whether pre
      existing depression rather than perioperative variables may predict postoperative
      reactive or persistent depression. METHODS: Overall, 96 patients completed a
      psychologic evaluation, including the Center for Epidemiologic Studies of
      Depression scale and the State and Trait Anxiety Inventory for depression and
      anxiety, respectively, before surgery and at 3-month follow-up. RESULTS: A total
      of 27 (28%) and 24 (25%) patients had depression preoperatively and at 3-month
      follow-up, respectively. Postoperative depression was predicted by preoperative
      scores in Center for Epidemiologic Studies of Depression scale (beta = 0.29, p <
      0.05) and European System for Cardiac Operative Risk Evaluation (beta = 0.22, p <
      0.04), but not by procedure-related variables (p > 0.75). Specifically, patients
      with reactive depression showed greater European System for Cardiac Operative
      Risk Evaluation than those without depression (p < 0.05), whereas patients with
      persistent depression had greater preoperative Center for Epidemiologic Studies
      of Depression scores than those whose depression improved after surgery (p <
      0.01). CONCLUSIONS: The severity of pre-existing depression and biomedical risk
      factors can be markers of depression-related risk 3 months after cardiac surgery
      in patients with persistent and reactive depression, respectively. An integrated
      psychologic and biomedical evaluation is essential to anticipate which patients
      are likely to show depression after cardiac surgery.

PMID- 24673941
TI  - Medication-induced diabetes during induction treatment for ALL, an early marker
      for future metabolic risk?
AB  - Medication-induced diabetes (MID) is seen in children treated for acute
      lymphoblastic leukemia (ALL) mostly during induction, due to the use of l
      asparaginase and glucocorticoids. Our objective was to assess whether MID during
      induction, is a risk factor for future impaired glucose tolerance (IGT),
      diabetes, or metabolic syndrome. Ninety survivors of pediatric ALL, ages 10 yr
      and older were recruited, 30 with history of MID and 60 controls. Waist/height
      ratio >0.5 was considered as an increased risk for central adiposity and insulin
      resistance. Lipid profile and an oral glucose tolerance test (OGTT) were
      performed. Study patients were older than controls (17.2 vs. 14.9, p < 0.05). The
      groups had similar sex distribution, body mass index (BMI) z-score, and Tanner
      staging. A waist/height ratio of >0.5 was seen in 60 and 31.7% of the study and
      control groups, respectively (p = 0.01). Increased frequency of IGT in the study
      group compared with the control group was seen (13.3 and 1%, respectively) (p =
      0.07). We observed a trend toward higher proportion of patients with multiple
      features of metabolic syndrome in the study compared with control group (16.7 vs.
      5%, p = 0.09). In conclusion, MID during induction may be an early marker for
      metabolic disturbances later in life. The higher rates of increased waist/height
      ratio, and subjects with multiple metabolic syndrome features, may predict a
      metabolic risk in children with history of MID. Rates of IGT were four fold
      higher in the study group although not statistically significant. MID may be a
      'red flag' indicating the need for ongoing metabolic screening and lifestyle
      modifications to prevent future metabolic disease. 

PMID- 24673942
TI  - Editor's Note.

PMID- 24673943
TI  - Commentary: How radiation damages teeth: Getting to the root of the problem.

PMID- 24673944
TI  - Novel technique for simulation and external beam treatment planning for obese
      patients.
AB  - PURPOSE: In computed tomography (CT)-guided radiation treatment planning, an
      accurate assessment of a patient's external contour is needed to determine the
      number of monitor units appropriate to treat a target volume to the prescribed
      dose. When obese patients are imaged, even using a large-bore CT scanner, lateral
      tissues frequently fall outside the field of view of the CT scanner, which makes
      it difficult to accurately calculate the dose needed for lateral or oblique
      treatment fields. We aimed to develop a technique to capture the external contour
      of patients in whom traditional simulation techniques would fail to capture part
      of the anatomy. METHODS AND MATERIALS: The following technique was used in
      multiple patients. The patient was centered on the CT couch, and an isocenter was
      placed. The initial scan was obtained with the isocenter at the central position
      on the table. Two subsequent scans were obtained with the patient first shifted
      right on the table and then shifted left. The 3 CT scans were fused using a CT-CT
      cross-correlation algorithm. The accuracy of the scans was reviewed manually.
      Using the fused scans, lateral tissues were contoured on the primary scan and
      assigned a density of 1 g/cm(3). RESULTS: With this technique, each patient's
      entire body contour was available on a single fused scan. The availability of the
      entire body contour on the scan allowed for treatment planning with a 360-degree
      freedom for external beam placement. CONCLUSIONS: This novel approach of fusing
      multiple CT scans allows for the external anatomy of obese patients to be
      completely captured. The increase in available beam angles made possible by this
      approach can optimize external beam treatment planning, including planning for
      intensity-modulated radiation therapy.

PMID- 24673945
TI  - Comparison of daily cone-beam computed tomography and kilovoltage planar imaging
      for target localization in prostate cancer patients following radical
      prostatectomy.
AB  - PURPOSE: To review our initial clinical experience with image-guided radiation
      therapy (IGRT) using cone-beam computed tomography (CBCT) for prostate bed
      localization in post-radical prostatectomy (RP) patients and to compare shift and
      acute toxicity results to our previously published IGRT experience with daily kV
      planar imaging. METHODS AND MATERIALS: Fifty patients treated with intensity
      modulated radiation therapy (IMRT) who had image guidance using either CBCT (n =
      23) or kV planar imaging (n = 27) following RP were analyzed. Shifts were
      recorded in anterior-posterior, superior-inferior, and left-right axes. Total
      error was defined as the shift from initial setup based on skin markings to
      isocenter. Prostate bed motion (PBM) was defined as the change in prostate bed
      position relative to bones. Acute toxicity was graded according to the Radiation
      Therapy Oncology Group morbidity criteria. RESULTS: Total error (TE) was measured
      in 752 CBCTs and 725 kV planar image pairs. PBM was measured in 585 CBCTs and 384
      kV planar image pairs. The average magnitudes of TE and PBM in the anterior
      posterior, superior-inferior, and left-right axes were greater with kV planar
      imaging compared to CBCT. Frequencies of acute grade 2 gastrointestinal (13% vs
      7%, P = .7) and genitourinary (9% vs 11%, P = 1.0) were similar for CBCT and kV
      planar imaging patients. No toxicities greater than grade 2 were seen.
      CONCLUSIONS: These results suggest that although the magnitudes of TE and PBM
      were larger with kV planar compared to CBCT, the levels of acute toxicity were
      acceptable and comparable between the two. The reasons for the differences are
      unclear, but we postulate that discernment of the prostate bed on the CBCT is
      more difficult. Further investigation is necessary to determine the reason for
      the shift differences and to evaluate the benefits and risks of CBCT in this
      setting.

PMID- 24673946
TI  - Comparative analysis of volumetric modulated arc therapy versus intensity
      modulated radiation therapy for radiotherapy of anal carcinoma.
AB  - PURPOSE: Volumetric modulated arc therapy (VMAT), an evolution of intensity
      modulated radiation therapy (IMRT), utilizes the dynamic modulation of angular
      dose rate through changes in gantry speed, linear accelerator dose rate, and
      multileaf collimator motion to deliver a treatment fraction in rotational fashion
      with improved efficiency and in shorter time. In general, target coverage
      relative to adjacent organ-at-risk sparing is highly dependent on the complexity
      of the treatment site. Therefore, we critically evaluated VMAT compared to IMRT
      for definitive treatment of anal carcinoma with respect to dosimetry and
      efficiency. METHODS AND MATERIALS: Using SmartArc (Philips Healthcare, Andover,
      MA), VMAT treatment plans were generated for 10 patients treated at our
      institution for anal carcinoma, and compared to the IMRT plans used for clinical
      treatment. The patients were all female, had T classification TX/1 (n = 5), T2 (n
      = 3) or T3 (n = 2), were node-negative (n = 6) or node-positive (n = 4), and were
      treated to a total dose of 50 to 58 Gy. Pairwise comparisons were made between
      VMAT and IMRT plans with respect to dose-volume histogram parameters relating the
      dose received by target volumes, relevant organs at risk, and normal tissues. The
      plans were machine-delivered, with actual beam delivery times measured. RESULTS:
      VMAT plans had superior planning target volume coverage and dose homogeneity,
      with improved conformality in treatment of the elective nodal volume, in
      comparison to IMRT. Mean dose to the small bowel, genitalia, and femoral heads
      were significantly lower with VMAT, and similar with respect to bladder, pelvic
      bones, and normal tissues. Integral dose was comparable between the 2 techniques.
      VMAT plans required 36.8% fewer monitor units, and beam delivery time was shorter
      by 9 minutes. CONCLUSIONS: Our results indicate that VMAT represents an ideal
      treatment modality for anal carcinoma, generating plans with excellent target
      coverage, lower doses to organs at risk, and shorter treatment times, in
      comparison to IMRT.

PMID- 24673947
TI  - An early report on outcomes from computed tomographic-based high-dose-rate
      brachytherapy for locally advanced cervix cancer: A single institution
      experience.
AB  - PURPOSE: To report our experience using high-dose-rate (HDR) brachytherapy with
      computed tomographic (CT) imaging for locally advanced cervix cancer, using
      available resources to optimize the treatment. METHODS AND MATERIALS: Fifty-seven
      women with cervix cancer were treated between September 2004 and March 2008.
      Patients received external radiotherapy, HDR brachytherapy (7 Gy x4) and
      concurrent chemotherapy. CT planning was done for each insertion. RESULTS: Median
      age was 53 years (range, 29-89 years); majority (49%) had International
      Federation of Gynecology and Obstetrics stage IIB. The median follow-up was 22.6
      months. There were 4 patients who required laser coagulation for rectal bleeding,
      and one patient required hemicolectomy for sigmoid stricture. There was no grade
      3 or 4 genitourinary toxicity. The Kaplan-Meier overall survival, relapse free,
      central pelvic and pelvic control at 3 years was 86%, 62%, 89%, and 83%,
      respectively. Pelvic control for tumors 2 to 5 cm was 95% and 84% for tumors
      greater than 5 cm. CONCLUSIONS: Our early experience confirms that CT-based HDR
      brachytherapy for cervix cancer achieves disease control comparable to other
      published series. At the same time, conformal avoidance of organs at risk allows
      for low rates of toxicity.

PMID- 24673948
TI  - Radiation therapy for leukemia cutis.
AB  - PURPOSE: Leukemia cutis (LC) is the infiltration of the epidermis, dermis, or
      subcutis by neoplastic leukocytes, resulting in clinically identifiable cutaneous
      lesions. Electron-based radiation therapy (RT) is often used in the treatment of
      LC; however, modern studies of RT are lacking. We reviewed our experience to
      analyze treatment response, disease control, and toxicity associated with RT in
      order to develop treatment recommendations for patients with LC. METHODS AND
      MATERIALS: Fifteen patients who underwent treatment for LC at our institution
      from November 1994 to August 2009 were identified and their medical records were
      reviewed and analyzed. RESULTS: LC presented after a median of 2 (range 0-24)
      months from acute myeloid leukemia diagnosis. Median survival from time of LC
      presentation was 23 months (range 0.5-137 months). Thirteen courses of radiation
      were administered to 12 patients: 9 total skin electron beam (TSEB) therapy and 4
      focal treatments. Of patients receiving TSEB, 89% had diffuse LC involvement and
      67% were in marrow remission. By contrast, only 25% of patients receiving focal
      therapy had diffuse LC involvement and only 25% were in marrow remission. Median
      TSEB dose was 1600 (range 600-2400) cGy. Fifty percent of patients had a complete
      response to RT but 1-year local control was only 33%. All patients who developed
      a skin relapse either had active marrow disease at the time of RT or marrow
      recurrence shortly thereafter. Median survival since RT was 5 (range 0.5-136)
      months. RT was well tolerated without significant acute effects; however, 1
      patient receiving chemotherapy developed radiation recall 1 month after RT.
      CONCLUSIONS: Patients with LC have aggressive disease with few long-term
      survivors. Definitive treatment with TSEB should be utilized only in cases of
      marrow remission with focal electron therapy reserved for palliation of
      symptomatic lesions. Long-term prognosis and durable cutaneous remission is
      dependent on systemic disease control.

PMID- 24673949
TI  - Commentary: Safety considerations in contemporary radiation oncology:
      Introduction to a series of ASTRO safety white papers.

PMID- 24673950
TI  - The role of radiation therapy in uterine-confined endometrial carcinoma.
AB  - The treatment of endometrial cancer begins with surgery, including total
      abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal lavage, and a
      consideration for lymph node evaluation. Selection of adjuvant therapy is based
      on an approximation of the risk of recurrence with features such as stage, tumor
      histology, lymphovascular space invasion, and patient age. The role of adjuvant
      radiation therapy in patients with intermediate risk of recurrence is a matter of
      ongoing controversy. Several randomized trials indicate that adjuvant radiation
      therapy improves loco-regional control. However, the ideal form of radiation
      therapy in these patients continues to be under debate. 

PMID- 24673951
TI  - Chemotherapy-refractory cutaneous Langerhans cell histiocytosis treated with
      radiotherapy.

PMID- 24673952
TI  - Radiation recall associated with insulin growth factor 1R antibody.

PMID- 24673953
TI  - eLQ : A biologically-equivalent dose calculator available on iPhone, Android, and
      the web.

PMID- 24673954
TI  - The prevalence of suicidal ideation among the elderly in China: a meta-analysis
      of 11 cross-sectional studies.
AB  - OBJECTIVE: This study aimed to estimate the pooled prevalence of suicidal
      ideation among Chinese elderly aged >= 60 years. METHODS: Two reviewers
      independently searched the potentially relevant studies through electronic
      database (PubMed-Medline, Embase, Wanfang Data, Chinese National Knowledge
      Infrastructure and Chongqing VIP) using key terms 'suicid', 'suicidal ideation'
      combined with 'aged', 'elderly' and 'old people'. All selected studies should
      meet the eligibility criteria in this study. Chi-square based Q test and I(2)
      statistic assessed the heterogeneity. Forest plots were used to display results
      graphically. Potential publication bias was assessed by the funnel plot and
      Begg's test. Prevalence rate was meta-analysed. RESULTS: In total, 11 studies
      were included with 11,526 subjects. The prevalence of suicidal ideation among
      Chinese elderly ranged from 2.2% to 21.5%. The pooled prevalence of all 11
      studies was 11.5% (95% CI: 8.3%-14.8%). Subgroup analyses showed the prevalence
      for males was 11.0%, and for the females was 15.6%. In three subgroups for age,
      60-69, 70-79 and >= 80, the prevalence was 9.1%, 12.1% and 18.9% respectively. A
      slightly higher prevalence in rural areas was calculated than in urban (14.7% vs.
      11.8%). In mainland China, the prevalence was 12.6%. And in Taiwan and Hongkong,
      the pooled prevalence was 9.2%. CONCLUSIONS: The prevalence of suicidal ideation
      was relatively high among elderly in China, and it should attract enough
      attention.

PMID- 24673955
TI  - Conduits in coronary artery bypass grafting.
AB  - Modern cardiac practice in the United States is conservative when it comes to
      using bilateral internal mammary or radial artery grafts in coronary artery
      bypass surgery. Here, we examine the evidence regarding using other arterial
      grafts instead of veins as a complement to left internal mammary artery in
      surgical revascularization. In addition, we put our report in perspective
      relative to prevailing practice, professional societal guidelines, and future
      directions in coronary artery bypass grafting. 

PMID- 24673956
TI  - The Affordable Care Act: implications for cardiothoracic surgery.
AB  - The Affordable Care Act legislation that was passed by the US Congress and signed
      into law by President Obama on March 23, 2010 is having a substantial effect
      throughout all of health care in the United States. Cardiothoracic surgeons, as
      hospital-based procedural specialists, bring unique assets and certain important
      liabilities into this massive restructuring of our health care delivery system.
      This article highlights how each of the 10 titles in the Obamacare legislation
      might affect our specialty; its collaborative relationship with our
      cardiovascular, medical specialty, and primary care colleagues; and our clinical
      practice roles and responsibilities in accountable care organizations and primary
      care medical homes. This article also addresses the unique assets in clinical
      data in medicine and quality improvement demonstrated by our specialty that have
      been used to help shape the current and future landscape. Finally, key resources
      are identified to allow the cardiothoracic community to monitor the ongoing
      progress of Obamacare as implementation begins. Keeping abreast of these rapidly
      changing developments will be an important role for our specialty societies and
      for practitioners alike going forward. 

PMID- 24673957
TI  - Modern management of empyema thoracis.

PMID- 24673958
TI  - Stereotactic radiotherapy for pulmonary metastases.
AB  - The most common treatment of pulmonary metastasis for solid tumors employs
      systemic chemotherapy, hormonal therapy, or biologic agents. Some series have
      suggested that aggressive surgical resection of pulmonary metastasis may improve
      patient outcomes in terms of quality of life and overall survival. Recently, data
      from clinical trials and retrospective series support the use of aggressive local
      control with high conformal dose radiotherapy (stereotactic body radiation
      therapy) in patients with limited metastases or oligometastases. Further evidence
      suggests that these patients represent a distinct clinical and biological class
      of patients. This review focuses on the role of ablative doses of radiotherapy in
      the treatment of pulmonary metastases. Specifically we discuss the rationale,
      treatment delivery, and local control that have led to the ongoing randomized
      clinical trials attempting to demonstrate a benefit over the current palliative
      standard of care. 

PMID- 24673959
TI  - Surgical treatment of hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a unique primary myocardial disease
      characterized by unexplained left ventricular hypertrophy in absence of another
      etiology. One of the key features is the presence of systolic anterior motion of
      the anterior leaflet of the mitral valve which causes left ventricular outflow
      tract obstruction with various degrees of mitral valve regurgitation. Surgical
      septal myectomy is the preferred treatment of choice if medical treatment is
      unsuccessful or intolerable. We summarize in this review the available treatment
      options for HCM. 

PMID- 24673961
TI  - Current readings: surgical repair experience of congenital chest wall
      deformities.
AB  - Major advancements have been made in the surgical repair of congential chest wall
      deformities. This review highlights selected readings of the experience in
      correction of pectus excavatum and pectus carinatum. In particular, it summarizes
      the current standard of care and outcomes of new and modified procedures for
      patients with chest wall deformities. 

PMID- 24673960
TI  - Bicuspid aortic valve and associated aortopathy: an update.
AB  - Bicuspid aortic valve (BAV) is the most common form of congenital heart disease
      and most such patients develop cardiovascular complications over time. Recent
      studies have shed light on one of the most common of these complications, BAV
      associated aortopathy. Two distinct BAV phenotypes have been identified, which
      may have different causes of their associated aortopathy. Increasing evidence
      suggests that the BAV stenosis phenotype is predominantly secondary to
      hemodynamic perturbances in transvalvular flow and is associated with a more
      benign long-term prognosis once the stenotic BAV is replaced. In contrast, the
      root phenotype--which is associated with aortic insufficiency--appears to have a
      genetic origin and may be associated with a higher risk of adverse aortic
      complications, irrespective of the extent of valvular disease. Such observations
      may have implications for patient decision making. Future studies should be
      performed so as to better define phenotypes and risk factors for BAV-associated
      aortopathy.

PMID- 24673962
TI  - Current readings: computed tomography screening for lung cancer.
AB  - Computed tomography screening for lung cancer is rapidly transitioning from the
      research realm to the clinical arena, but important questions remain regarding
      the ideal selection criteria, the optimal frequency and duration of screening,
      and other factors. The purpose of this review is to familiarize readers with
      recently published articles that address computed tomography screening for lung
      cancer and other synergistic methods to reduce mortality among individuals with a
      history of tobacco use. In this review, we summarize the key points from each
      article and discuss the relevance of these findings for thoracic surgeons. The
      articles reviewed here add to the growing body of knowledge about screening and
      have the potential to help maximize the benefits of screening while minimizing
      the risks. 

PMID- 24673963
TI  - Current readings: blood-based biomarkers for lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths worldwide largely owing to
      diagnosis of the disease at an advanced stage. Recent advances in blood-based
      biomarker research have the potential to reduce mortality by providing a means
      for detecting lung cancer at an earlier stage. Since the publication of the
      National Lung Cancer Screening Trial demonstrating reduction in mortality with
      computed tomography (CT) scan screening, the U.S. Preventive Services Task Force
      has released a draft statement recommending annual low-dose CT scan screening for
      high-risk patients. However, CT screening has a high false-positive rate leading
      to the need for additional imaging and invasive procedures. In this article, we
      review recent literature on blood-based lung cancer biomarkers that we believe
      will have a significant role in enhancing screening efficacy in the near future. 

PMID- 24673964
TI  - Seminars in Thoracic and Cardiovascular Surgery: Roundtable discussion on TAVR.

PMID- 24673965
TI  - Low-dose splenic irradiation in symptomatic congestive splenomegaly: report of
      five cases with literature data.
AB  - BACKGROUND: To show effectiveness of low-dose splenic irradiation in symptomatic
      congestive splenomegaly. METHODS: Five patients were referred to our department
      for symptomatic congestive splenomegaly within three years. Primary diseases were
      autoimmune hepatitis with liver cirrhosis (n=2), cystic fibrosis (n=1),
      granulomatous liver disease (n=1) and Werlhof disease with liver cirrhosis (n=1).
      Mean age was 54 years (range: 36-67). Patients received splenic irradiation with
      a total dose of 3 Gy (single dose: 0.5 Gy). One patient was re-irradiated after
      long-term failure with the same treatment schedule. RESULTS: In four patients
      long term relief of splenic pain could be observed during the follow-up time of
      median 20 (range: 2-36) months. Four patients showed haematological response
      after irradiation with an increase of erythrocytes, leucocytes and/or platelets.
      A slightly decrease in spleen size was found in two patients. CONCLUSIONS: Low
      dose splenic irradiation in symptomatic congestive splenomegaly is feasible and
      perhaps as effective as in lympho-and myeloproliferative malignancies regarding
      pain relief and haematological response.

PMID- 24673966
TI  - Intensive chemotherapy and reduced-intensity allogeneic hematopoietic stem cell
      transplantation for acute myeloid leukemia in elderly patients.
AB  - AIMS: Acute myeloid leukemia (AML) incidence increases with age, yet treatment of
      elderly patients has reduced efficacy compared with younger patients and is often
      poorly tolerated. This retrospective study assessed the outcomes of older
      patients with AML treated with intensive chemotherapy with or without allogeneic
      hematopoietic stem cell transplantation (HSCT). METHODS: We identified all adult
      patients>=60 years with newly diagnosed AML treated with induction chemotherapy
      at our institutions between February 1999 and July 2011. Institutional databases
      and medical records were used to collect information on baseline characteristics,
      chemotherapy protocols, response to therapy, relapse-free survival (RFS) and
      overall survival (OS). RESULTS: Three hundred and forty-five patients>=60 years
      were diagnosed with AML, including 172 patients (49.9%) who received intensive
      induction chemotherapy. The median age of intensively treated patients was 66
      years (range 60-83 years). Responses to one to two cycles of induction
      chemotherapy were complete remission (CR) in 70.3% of patients, refractory
      disease in 15.1% and induction death in 14.5%. At a median follow-up of 22 months
      for survivors, intensive induction chemotherapy resulted in 3-year RFS of 20.2%,
      and 3-year OS of 24.0%. Seventeen patients (14.0% of patients in CR1) proceeded
      to allogeneic HSCT in first remission. These patients experienced 3-year RFS of
      63.5% and 3-year OS of 77.5%. CONCLUSION: Intensive induction chemotherapy for
      newly diagnosed AML in older patients is feasible and effective in a proportion
      of patients, and those selected for allogeneic transplantation in CR1 may
      experience particularly favorable survival outcomes.

PMID- 24673967
TI  - Reply to the letter to the editor regarding Bradbrook et al. (2013).

PMID- 24673968
TI  - Development of a model to estimate 24-hour urinary creatinine excretion.
AB  - The accuracy of the spot urine analyte/creatinine ratio in estimating 24-hour
      excretion of the analyte is compromised because it is not adjusted for 24-hour
      creatinine excretion. The authors developed a model for conveniently estimating
      24-hour creatinine excretion. The model was derived from 24-hour urine
      collections using multiple linear regression, including sex, weight, race, and
      age. The model was then evaluated in a validation cohort, assessing the
      correlation between estimated and measured 24-hour creatinine excretion and by
      comparing their correlation with muscle mass. Estimated creatinine excretion
      correlated strongly with measured creatinine excretion (r=0.80 in the entire
      cohort and 0.93 after eliminating patients with incomplete collections), and
      correlated at least as strongly as measured creatinine excretion with lean muscle
      mass (r=0.94 vs r=0.82, respectively). Adjusting spot urine analyte/creatinine
      ratios using the estimated 24-hour creatinine excretion by this convenient method
      can improve the accuracy of estimating 24-hour excretion of albumin, sodium, and
      other analytes. 

PMID- 24673969
TI  - Sleep-disordered breathing is associated with elevated human atrial natriuretic
      peptide levels in a Japanese urban population: the Suita study.

PMID- 24673970
TI  - Typical and atypical coronary heart disease deaths and their different
      relationships with risk factors. The Gubbio residential cohort study.
AB  - OBJECTIVES: The Seven Countries Study showed that fatal coronary heart disease
      (CHD) with only chronic heart failure, arrhythmia or blocks (atypical CHD, A-CHD)
      may represent a distinct disease as compared to fatal CHD cases with angina
      pectoris, acute myocardial infarction (AMI) or sudden death (typical CHD, T-CHD).
      We aimed at validating this, using identical diagnostic criteria, in a separate
      residential cohort first examined in 1983-85 in Gubbio, central Italy. MATERIAL
      AND METHODS: Forced Cox's models were run to assess 9 classic risk factors and
      their 20-year predictivity of A-CHD versus T-CHD, in the entire cohort or
      separately for men and women. RESULTS: There were 3229 subjects aged 30-79 years.
      Entry mean age was slightly higher in women than men although age at death was
      lower in men than in women for both T-CHD (71.99 +/- 11.38 versus 81.20 +/- 9.35
      years, p<0.0001) and A-CHD (80.22 +/- 9.44 versus 84.98 +/- 8.13 years,
      p<0.0001). T-CHDs were predicted by male gender, age, continued smoke, systolic
      blood pressure (SBP), blood glucose, total and HDL-cholesterol (protective). A
      CHDs were predicted by age, continued smoke, SBP, body mass index and blood
      glucose but neither total nor HDL-cholesterol or gender was significant. In the
      entire cohort and in men there were predictive differences of T-CHD versus A-CHD
      fatalities only in relation to age (p<0.01), SBP (p<0.05) and total cholesterol
      (p<0.01). CONCLUSION: As age, SBP and total cholesterol had a different
      predictive role of T-CHD versus A-CHD fatalities also in the Gubbio cohort, the
      possibility is reinforced that a different etiology exists between these
      entities.

PMID- 24673971
TI  - Lung squamous cell carcinoma metastasizing to the nasopharynx following
      bronchoscopy intervention therapies: a case report.
AB  - Metastatic carcinoma to the nasopharynx is extremely rare, and few cases have
      been reported in the literature. In the present report, we describe the case of a
      patient with a mass in the nasopharynx found by bronchoscopy. Our patient was a
      61-year-old man receiving multiple bronchoscopy intervention therapies for
      advanced lung squamous cell carcinoma (SCC), which was histopathologically
      confirmed. The SCC metastasized to the nasopharynx following the bronchoscopy
      intervention therapies. The lesion was considered metastatic from lung cancer on
      the basis of clinical and histological clues. The exact mechanism of lung cancer
      metastasis to the nasopharynx in this case remains unclear because either
      implantation or hematogenous and lymphatic spread is possible. A thorough head
      and neck examination should be undertaken during bronchoscopic evaluation,
      especially in patients receiving bronchoscopy intervention therapies. The early
      detection of a silent nasopharyngeal metastasis is important to choosing from
      among the multiple treatment options available. 

PMID- 24673972
TI  - A new pathway of exogenous fatty acid incorporation proceeds by a classical
      phosphoryl transfer reaction.
AB  - The Firmicute bacteria readily incorporate exogenous fatty acids into their
      phospholipids. In some (but not all) family members incorporation of the fatty
      acids present in human serum precludes the use of fatty acid synthesis inhibitors
      to treat infections. However, the pathway(s) of exogenous fatty acid
      incorporation in these bacteria remained unknown, although it was thought to
      differ from known pathways. Parsons and co-workers show that in Staphylococcus
      aureus exogenous fatty acids are activated by phosphoryl transfer from ATP to
      form acyl-phosphates, a mixed anhydride suggested as a potential intermediate 70
      years ago. This finding has important ramifications for the efficacy of treatment
      of S. aureus infections using inhibitors of fatty acid synthesis.

PMID- 24673973
TI  - Pan-European early switch/early discharge opportunities exist for hospitalized
      patients with methicillin-resistant Staphylococcus aureus complicated skin and
      soft tissue infections.
AB  - The objective of this study was to document pan-European real-world treatment
      patterns and healthcare resource use and estimate opportunities for early switch
      (ES) from intravenous (IV) to oral antibiotics and early discharge (ED) in
      hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA)
      complicated skin and soft tissue infections (cSSTIs). This retrospective
      observational medical chart review study enrolled 342 physicians across 12
      European countries who collected data from 1542 patients with documented MRSA
      cSSTI who were hospitalized (July 2010 to June 2011) and discharged alive (by
      July 2011). Data included clinical characteristics and outcomes, hospital length
      of stay (LOS), MRSA-targeted IV and oral antibiotic use, and ES and ED
      eligibility according to literature-based and expert-validated criteria. The most
      frequent initial MRSA-active antibiotics were vancomycin (50.2%), linezolid
      (15.1%), clindamycin (10.8%), and teicoplanin (10.4%). Patients discharged with
      MRSA-active antibiotics (n = 480) were most frequently prescribed linezolid
      (42.1%) and clindamycin (19.8%). IV treatment duration (9.3 +/- 6.5 vs. 14.6 +/-
      9.9 days; p <0.001) and hospital LOS (19.1 +/- 12.9 vs. 21.0 +/- 18.2 days; p
      0.162) tended to be shorter for patients switched from IV to oral treatment than
      for patients who received IV treatment only. Of the patients, 33.6% met ES
      criteria and could have discontinued IV treatment 6.0 +/- 5.5 days earlier, and
      37.9% met ED criteria and could have been discharged 6.2 +/- 8.2 days earlier.
      More than one-third of European patients hospitalized for MRSA cSSTI could be
      eligible for ES and ED, resulting in substantial reductions in IV days and bed
      days, with potential savings of ?2000 per ED-eligible patient.

PMID- 24673974
TI  - Perception of cervical cancer risk and screening behavior: a literature review.
AB  - PURPOSE: This review examines women's risk perception of cervical cancer, the
      factors influencing this perception, and the relationship between risk perception
      of cervical cancer and screening behavior. METHODS: Integrative literature review
      method was used. FINDINGS: The search procedure resulted in the identification of
      42 studies, including 1 literature review and 41 primary studies. Trends and
      discrepancies in the literature are presented with interpretations and
      recommendations. CONCLUSION: Existing theories of health behavior appear
      inadequate for understanding screening behavior, and further studies are
      recommended to enrich the knowledge base of nursing diagnoses in knowledge
      deficit and health-seeking behavior. IMPLICATIONS FOR NURSING PRACTICE: Efforts
      would be made to improve nurses' understanding of risk perception of cervical
      cancer within specific cultural context.

PMID- 24673975
TI  - Development and evaluation of a baseline-event-anticipation score for hepatitis
      delta.
AB  - Hepatitis delta is considered the most severe form of viral hepatitis, but
      variables associated with disease progression are poorly defined. This study
      aimed to identify risk factors associated with worse clinical outcome in patients
      with hepatitis delta and to develop a clinical score to determine their risk of
      experiencing liver-related morbidity or mortality. We followed 75 HBsAg-anti-HDV
      positive patients with hepatitis delta for up to 16 years (median 5 years). The
      baseline-event-anticipation score (BEA score) was developed based on variables
      associated with the development of liver-related clinical complications. Age,
      region of origin, presence of cirrhosis, albumin, INR, hyperbilirubinemia and
      thrombocytopenia were all associated with the development of an event in the
      training cohort. The BEA score included age, sex, region of origin, bilirubin,
      platelets and INR. Points were allocated according to hazard ratios, and three
      risk groups were defined: BEA-A mild risk, BEA-B moderate risk and BEA-C high
      risk. Hazard ratios of BEA-B and BEA-C patients for liver-related clinical
      endpoints were 9.01 and 25.27 vs BEA-A with an area under curve of the receiving
      operating characteristic curve of 0.88. The accuracy of the BEA score was
      confirmed in two independent validation cohorts followed in Barcelona (n = 77)
      and Dusseldorf (n = 62). Delta hepatitis is associated with a very severe long
      term outcome. The BEA score is easy to apply and predicts with a very high
      accuracy the development of liver-related complications in patients with
      hepatitis delta.

PMID- 24673976
TI  - Fate of arsenate following arsenite oxidation in Agrobacterium tumefaciens GW4.
AB  - The fate of arsenate (As(V) ) generated by microbial arsenite (As(III) )
      oxidation is poorly understood. Agrobacterium tumefaciens wild-type strain (GW4)
      was studied to determine how the cell copes with As(V) generated in batch
      culture. GW4 grown heterotrophically with mannitol used As(III) as a supplemental
      energy supply as reflected by enhanced growth and increased cellular levels of
      NADH and ATP. Under low phosphate (Pi) conditions and presence of As(III)
      oxidation, up to ~ 50% of the resulting As(V) was taken up and found associated
      with the periplasm, membrane or cytoplasm fractions of the cells. Arsenic was
      found associated with proteins and polar lipids, but not in nucleic acids or
      sugars. Thin-layer chromatography and gas chromatography-mass spectrometry
      analysis suggested the presence of arsenolipids in membranes, presumably as part
      of the bilayer structure of the cell membrane and replacing Pi under Pi-limiting
      conditions. The potential role of a Pi-binding protein (PstS) for As(V) uptake
      was assessed with the His-tag purified protein. Intrinsic tryptophan fluorescence
      spectra analysis suggests that PstS can bind As(V) , but with lower affinity as
      compared with Pi. In early stationary phase cells, the As(V)  : Pi ratio was
      approximately 4.3 and accompanied by an altered cell ultrastructure.

PMID- 24673977
TI  - Percutaneous treatment of cervical and lumbar herniated disc.
AB  - Therapeutic armamentarium for symptomatic intervertebral disc herniation includes
      conservative therapy, epidural infiltrations (interlaminar or trans-foraminal),
      percutaneous therapeutic techniques and surgical options. Percutaneous,
      therapeutic techniques are imaging-guided, minimally invasive treatments for
      intervertebral disc herniation which can be performed as outpatient procedures.
      They can be classified in 4 main categories: mechanical, thermal, chemical
      decompression and biomaterials implantation. Strict sterility measures are a
      prerequisite and should include extensive local sterility and antibiotic
      prophylaxis. Indications include the presence of a symptomatic, small to medium
      sized contained intervertebral disc herniation non-responding to a 4-6 weeks
      course of conservative therapy. Contraindications include sequestration,
      infection, segmental instability (spondylolisthesis), uncorrected coagulopathy or
      a patient unwilling to provide informed consent. Decompression techniques are
      feasible and reproducible, efficient (75-94% success rate) and safe (>0.5% mean
      complications rate) therapies for the treatment of symptomatic intervertebral
      disc herniation. Percutaneous, imaging guided, intervertebral disc therapeutic
      techniques can be proposed either as an initial treatment or as an attractive
      alternative prior to surgery for the therapy of symptomatic herniation in both
      cervical and lumbar spine. This article will describe the mechanism of action for
      different therapeutic techniques applied to intervertebral discs of cervical and
      lumbar spine, summarize the data concerning safety and effectiveness of these
      treatments, and provide a rational approach for the therapy of symptomatic
      intervertebral disc herniation in cervical and lumbar spine. 

PMID- 24673978
TI  - Feasibility of slice width reduction for spiral cranial computed tomography using
      iterative image reconstruction.
AB  - PURPOSE: To prospectively compare image quality of cranial computed tomography
      (CCT) examinations with varying slice widths using traditional filtered back
      projection (FBP) versus sinogram-affirmed iterative image reconstruction
      (SAFIRE). MATERIALS AND METHODS: 29 consecutive patients (14 men, mean age: 72 +/
      17 years) referred for a total of 40 CCT studies were prospectively included.
      Each CCT raw data set was reconstructed with FBP and SAFIRE at 5 slice widths (1
      5mm; 1mm increments). Objective image quality was assessed in three predefined
      regions of the brain (white matter, thalamus, cerebellum) using identical regions
      of interest (ROIs). Subjective image quality was assessed by 2 experienced
      radiologists. Objective and subjective image quality parameters were
      statistically compared between FBP and SAFIRE reconstructions. RESULTS: SAFIRE
      reconstructions resulted in mean noise reductions of 43.8% in the white matter,
      45.6% in the thalamus and 42.0% in the cerebellum (p<0.01) compared to FBP on non
      contrast-enhanced 1mm slice width images. Corresponding mean noise reductions on
      1mm contrast-enhanced studies were 45.7%, 47.3%, and 45.0% in the white matter,
      thalamus, and cerebellum, respectively (p<0.01). There was no significant
      difference in mean attenuation of any region or slice width between the two
      reconstruction methods (all p>0.05). Subjective image quality of IR images was
      mostly rated higher than that of the FBP images. CONCLUSION: Compared to FBP,
      SAFIRE provides significant reductions in image noise while increasing subjective
      image in CCT, particularly when thinner slices are used. Therefore, SAFIRE may
      allow utilization of thinner slices in CCT, potentially reducing partial volume
      effects and improving diagnostic accuracy.

PMID- 24673980
TI  - Social media can revolutionise health care provider-patient relationship.

PMID- 24673979
TI  - Temporal evolution of multidetector CT findings after endoscopic submucosal
      dissection in patients with early gastric cancer: correlation with endoscopy.
AB  - OBJECTIVE: To assess changes over time in imaging findings retrospectively by
      multidetector CT (MDCT) with two-dimensional (2D) multiplanar reconstruction and
      three-dimensional (3D) CT gastrography (CTG), after endoscopic submucosal
      dissection (ESD) in patients with early gastric cancer (EGC), and to correlate 3D
      CT images with endoscopic appearance. MATERIALS AND METHODS: In this
      retrospective study, a total of 84 patients underwent ESD and were followed up
      with MDCT. Fifteen patients underwent CT twice, and 3 patients underwent CT 3
      times. A total of 105 CTs were included in this study and 43 CTs contained 3D
      CTGs. Two radiologists in consensus interpreted CT images for lesion
      detectability, presence and characteristics of ulcer, focal wall thickening,
      perigastric fat infiltration, and overlying enhancing layer in 2D images. The
      presence of ulcer or subtle mucosal nodularity, ulcer mound, and fold convergence
      were analysed in 3D CT images. We also assessed the time interval between ESD and
      CT and analysed the temporal evolution of CT findings. The sensitivity,
      specificity, and overall accuracy of 3D CTG were assessed regarding endoscopic
      features as the gold standard. RESULTS: The mean interval between ESD and follow
      up CT was 76.9 days (median, 62; range, 2-223). No tumour recurrence in any
      lesion was found on follow-up endoscopic biopsy and also lymph node or distant
      metastasis was not observed on CT exams in the follow-up period. The lesion
      detectability in a total of 105 post-ESD 2D CT images was 42.0% (44/105), and
      93.2% (41/44) of the detected lesions were visualizable 2 months after ESD. Focal
      wall thickening was observed during the entire follow-up period in all patients.
      Perigastric fat infiltration was observed in 4 lesions within 1 week of ESD.
      Overlying enhancing layer appeared in 27 lesions without temporal evolution. On a
      total of 43 post-ESD 3D CTG, lesion detectability was 76.7% (33/43), and lesions
      could be visualized for a longer period than by 2D CT images (223 days versus 99
      days). Three-dimensional imaging features revealed ulcer, ulcer mound, and fold
      convergence. Ulcer mounds disappeared first (median, 12.5 days; range, 2-14 days
      after ESD), ulcers appeared up to 4 months after ESD (median, 14 days; range, 2
      174 days after ESD) and fold convergence continued to the end of the study
      (median, 74 days; range, 2-223 days after ESD). We found that sensitivity,
      specificity, and overall accuracy of 3D CTG were 70.0%, 92.9%, 83.3% for ulcer,
      28.6%, 100%, 71.4% for ulcer mound, and 71.4%, 100%, 75% for fold convergence
      regarding endoscopy, respectively. CONCLUSION: On follow-up 2D or 3D CT images
      after ESD, early findings were of perigastric fat infiltration, ulcer, and
      surrounding oedema. Focal wall thickening and fold convergence continued to be
      observed late in the study. The overlying enhancing layer did not show temporal
      evolution.

PMID- 24673983
TI  - The value of prostate cancer support groups: a pilot study of primary physicians'
      perspectives.
AB  - BACKGROUND: In Canada, prostate cancer (PCa) is the most common male cancer, and
      prostate cancer support groups (PCSGs) have prevailed for more than 20 years
      providing support to men with PCa and their families. While the format, focus and
      benefits of attending PCSGs have been reported little is known about primary
      physicians' (PPs) perceptions of these groups. This article describes Canadian
      primary physicians' views about face-to-face and web-based PCSGs. METHODS:
      Canadian based primary physicians (n = 140) attending a 2012 Continuing Medical
      Education Conference participated in a pilot survey questionnaire study. The 56
      item questionnaire used in this study included six sets of attitudinal items to
      measure primary physicians' beliefs about positive and negative influences of
      PCSGs, reasons for attending PCSGs, the attributes of effective PCSGs, and the
      value of face-to-face and web-based PCSGs. RESULTS: Results showed that PCSGs
      were positively valued, particularly for information sharing, education and
      psychosocial support. Poor inclusivity, privacy, and accessibility were
      identified as potential barriers, and recommendations were made for better
      marketing and web-based PCSGs to increase engagement with potential attendees.
      CONCLUSIONS: Findings suggest PPs highly valued the role and potential benefits
      of PCSGs. Information provision and an educational role were perceived as key
      benefits amid the need to improve local and provincial marketing of PCSGs. The
      potential for web-based PCSGs to help in the support of PCa patients was also
      recognized.

PMID- 24673984
TI  - Description of alpha-1-antitrypsin deficiency associated with PI*Q0ourem allele
      in La Palma Island (Spain) and a genotyping assay for its detection.
AB  - By analysis of a case of discrepancy between serum alpha-1-antitrypsin (AAT)
      level and genotype for the most common defective alleles associated with AAT
      deficiency (PI*S and PI*Z), a patient carrying the allele PI*Q0ourem has been
      identified for the first time outside of Portugal. This null allele has been
      implicated in cases of severe pulmonary emphysema. After developing a clinical
      assay for detection of c.1130insT mutation, based on fluorescent probes
      (HybProbe(r)), another 4 carriers of PI*Q0ourem allele were identified among 43
      patients with abnormally low serum AAT levels based on their genotypes for PI*S
      and PI*Z alleles. Since 4 out 5 cases are from the same locality (La Palma
      Island, Spain), it is advisable to conduct genetic analyses of affected families
      and, possibly, a focused population screening.

PMID- 24673985
TI  - [Drug treatment of early-stage (de novo and "honeymoon") Parkinson disease].
AB  - In this article, we discuss the management of motor symptoms during the early
      phases of Parkinson's disease, excluding that of any other clinical
      manifestation. We relied primarily upon recently published data and do not
      describe older publications relating to anticholinergic drugs or amantadine. The
      initial pharmacological treatment of idiopathic Parkinson's disease (IPD) is
      symptomatic and remains based upon dopaminergic drugs. However, the development
      of new drugs has broadened the range of strategic options and improved overall
      patient management. Announcing the diagnosis is a critical moment, as pointed out
      by patients' associations. Patients should be advised to maintain personal,
      professional, social and physical activities as long as possible. The potential
      benefit of early pharmacological treatment should be explained, focusing on the
      possible disease-modifying effect of drugs such as rasagiline. According to
      current guidelines, L-Dopa is preferred in patients above 65years of age, while
      those below 65 should be treated with dopamine agonists. Like monoamine oxidase
      inhibitors B (MAOI-B), synthetic dopamine agonists exhibit several advantages:
      easy-to-use treatment with a once-daily administration, delayed L-Dopa
      initiation, significant efficacy on motor symptoms (although lower than that of L
      Dopa). MOAI can be prescribed in association with L-Dopa or dopamine agonists.
      Rasagiline also delays L-Dopa initiation, and consequently motor complications. 

PMID- 24673996
TI  - A Lotus japonicus mutant defective in nitrate uptake is also affected in the
      nitrate response to nodulation.
AB  - A chlorate-resistant mutant (Ljclo1) of the model legume Lotus japonicus was
      identified that showed normal levels of nitrate reductase enzyme activity but had
      decreased uptake of nitrate, as determined from nitrate depletion and
      electrophysiological measurements. The data suggest that the mutant could be
      affected specifically in the low-affinity but not in the high-affinity nitrate
      transport system, and also showed decreased uptake of chlorate. Back-crosses of
      the mutant plant to the wild type indicated that it is affected in a single
      Mendelian recessive trait. Thus, the mutation produced in Ljclo1 may be related
      to some of the low-affinity nitrate transporters or to a regulatory mechanism
      associated with nitrate/chlorate uptake. Both size and chlorophyll content in
      young leaves of the mutant plants were significantly reduced compared to the wild
      type. In addition, nodulation performance of the mutant plants was similar to the
      wild type in the absence of any exogenous nitrate. However, the nodule:root
      biomass ratio in mutant plants was considerably reduced in the presence of 1-2 mm
      nitrate. The levels of several transcripts for nitrate transport and assimilation
      genes were determined for the wild type and mutant plants and were slightly
      different. The results suggest interdependence between nitrate uptake, plant
      growth and nodulation in Ljclo1 mutant plants. 

PMID- 24673998
TI  - Editor's Note.

PMID- 24673999
TI  - Commentary: Regulating quality?

PMID- 24673997
TI  - Impact of patient-accessible electronic medical records in rheumatology: use,
      satisfaction and effects on empowerment among patients.
AB  - BACKGROUND: To measure the use, satisfaction and impact of a web portal which
      provides patients with rheumatoid arthritis home access to their electronic
      medical records (EMR). METHODS: A pretest-posttest study was conducted among 360
      patients. Questionnaires assessed socio-demographics, health literacy, Internet
      use, disease characteristics, patient-provider relationship and empowerment
      before and after launching a hospital-based patient web portal. To measure the
      impact of the portal, patients' satisfaction with care, trust in their
      rheumatologist, self-efficacy in patient-provider communication, illness
      perceptions, and medication adherence were assessed. The post-test included
      questions on portal use, satisfaction, and self-perceived impact due to portal
      use. RESULTS: 54% of respondents with Internet access had viewed their EMR.
      Respondents were positive about the ease of use and usefulness of the portal and
      reported very few problems. Age (P = .03), amount of Internet use (P = .01) and
      self-perceived Internet skills (P = .03) significantly predicted portal use. Of
      the respondents who had logged in, 44% reported feeling more involved in their
      treatment and 37% felt they had more knowledge about their treatment. Significant
      differences over time were not found on the empowerment-related instruments.
      CONCLUSIONS: The current portal succeeded in offering patients access to their
      EMR in a usable and understandable way. While its true impact is difficult to
      grasp, a relevant portion of the patients felt more involved in their treatment
      due to the web portal. Offering patients home EMR access, therefore, appears to
      be a valuable addition to the care process.

PMID- 24674001
TI  - Commentary: Adapting communication standards to enhance safety.

PMID- 24674000
TI  - Addressing connectivity issues: The Integrating the Healthcare Enterprise
      Radiation Oncology (IHE-RO) initiative.

PMID- 24674002
TI  - Observations on prostate intrafraction motion and the effect of reduced treatment
      time using volumetric modulated arc therapy.
AB  - PURPOSE: Intensity modulated radiation therapy (IMRT) has allowed accurate
      delivery of prostate radiotherapy; Volumetric modulated arc therapy (VMAT) offers
      an advancement of this technique with possible dosimetric advantages and delivery
      in a shorter time than standard IMRT. We hypothesize that treatment duration is a
      controllable factor associated with intrafraction target motion. METHODS:
      Included patients were treated for localized prostate cancer using IMRT or VMAT
      (RapidArc, Varian Medical Systems, Palo Alto, CA). Continuous motion data were
      monitored simultaneously using electromagnetic transponders (Calypso 4D
      Localization System, Calypso Medical Technologies, Inc, Seattle, WA).
      Displacements were recorded in the RL (right-left), SI (superior-inferior), and
      AP (anterior-posterior) directions at 10/second (Hz). Daily motion was reported
      as the mean (R) and 95th percentile (R95) displacement value for the entire
      session. Time effect was assessed by measuring daily displacement variables (R,
      R95) after each successive minute of treatment. RESULTS: Thirty-seven patients
      were included, accounting for 1332 treatment sessions. Mean session time was 7.4
      minutes (range, 0.5-37.2; interquartile range, 4.8-9.2). R (0.06, 0.08, 0.11,
      0.18) and R95 (0.14, 0.18, 0.23, 0.36) values (RL, SI, AP, 3-dimensional [3D],
      respectively) were evaluated for the entire cohort. Regression analysis showed
      treatment time to be the strongest predictor of observed displacements (P < .001
      AP, SI, 3D; P < 0.05 RL). Ninety-five displacements increased continuously from
      0.05 cm, 0.09 cm, 0.12 cm, and 0.16 cm after 1 minute to 0.21 cm, 0.20 cm, 0.29
      cm, and 0.47 after 10 minutes (RL, SI, AP, and 3D). Mean session time for VMAT
      was 4.6 minutes compared to 8.4 minutes for IMRT (difference = 3.8 min, P <
      .0001); VMAT was associated with reduced motion for both (difference = 0.02,
      0.03, 0.05, 0.07 cm) and (0.03, 0.04, 0.11, 0.12 cm) displacements. CONCLUSION:
      Our study is unique in exploring the role of session duration on intrafraction
      motion in the setting of electromagnetic transponders as well as VMAT. Our main
      results demonstrate that observed intrafraction prostate motion during
      radiotherapy is greater with increasing session time. Additionally, VMAT, due to
      shorter treatment sessions, resulted in significant reduction (30%-40%) in
      intrafraction displacements.

PMID- 24674003
TI  - Stereotactic radiosurgery-radiotherapy: Should Monte Carlo treatment planning be
      used for all sites?
AB  - PURPOSE: To evaluate a Monte Carlo (MC) treatment planning system for CyberKnife
      treatments of cranial and extracranial lesions and determine whether it is
      necessary for all treatment sites. Dose distributions are compared to those
      calculated with a ray-tracing algorithm. Maximum doses and dose-volume histograms
      for the target and selected critical structures are analyzed. METHODS AND
      MATERIALS: The CyberKnife is used for stereotactic radiosurgery-radiotherapy of
      intracranial lesions (91) as well as stereotactic body radiotherapy for lesions
      in the spine (24), lung (58), and pelvis (36). The Multiplan system is an inverse
      treatment planning system which uses an effective path length (EPL) algorithm
      (sometimes referred to as ray-trace) for dose calculations. In addition, an MC
      algorithm became clinically available in late 2007. RESULTS: The maximum doses
      calculated by the EPL to targets in the lung were uniformly larger than the doses
      calculated by MC by up to a factor of 1.32. In addition, large differences in
      target and critical organs' dose coverage were observed. In general, more beams
      traversing larger distances through low density lung are associated with larger
      differences. For other sites such as brain and pelvis targets the differences in
      maximum doses and tumor coverage were generally less than 5% between the 2
      calculation methods. CONCLUSIONS: The MC algorithm should be consistently used
      for treatment plans of lung lesions and lesions near large air cavities, but the
      faster EPL algorithm is adequate for treatment sites with less tissue
      heterogeneity.

PMID- 24674004
TI  - Early clinical outcomes for 3 radiation techniques for brain metastases: focal
      versus whole-brain.
AB  - PURPOSE: To present our novel technique for brain metastases (low-dose whole
      brain radiation therapy [WBRT] with simultaneous integrated boost (SIB) and
      focal, frameless stereotactic intensity modulated radiotherapy [IMRT]) in the
      context of patterns of failure, dosimetry, acute toxicity, and overall survival
      for 3 different radiation techniques. METHODS AND MATERIALS: We retrospectively
      reviewed 92 patients undergoing radiation for brain metastases via the following:
      (1) "prophylactic" WBRT to a low dose (median 30 Gy) with an SIB to the gross
      tumor volume plus 2-3 mm margin (median dose 45 Gy) in 10-15 fractions; (2)
      focal, frameless image-guided stereotactic IMRT (S-IMRT) in 5 fractions to tumor
      only (median 30 Gy); or (3) conventional (c)WBRT using 2 lateral opposed beams in
      10-15 fractions (30-37.5 Gy). The primary endpoints were local (LBC), distant
      (DBC), and total brain control (TBC) for each of the 3 types of brain radiation.
      Survival, toxicity, and dosimetry were reported as secondary endpoints. RESULTS:
      LBC was achieved in 72%, 78%, and 56% for SIB, S-IMRT, and cWBRT, respectively.
      DBC (ie, no new brain metastases) was observed in 92%, 67%, and 81% for SIB, S
      IMRT, and cWBRT, respectively. TBC (LBC + DBC) was 72%, 67%, and 56% for SIB, S
      IMRT, and cWBRT, respectively. No statistical difference in overall survival was
      observed (P = .067), and only 1 patient experienced biopsy proven radionecrosis.
      CONCLUSIONS: TBC after low-dose WBRT with SIB was acceptable and at least
      comparable to S-IMRT and cWBRT. SIB seems to be a safe and effective treatment
      strategy for patients with brain metastases and may efficiently combine the
      benefits of cWBRT and stereotactic radiosurgery.

PMID- 24674005
TI  - Radiotherapy for juvenile nasopharyngeal angiofibroma.
AB  - PURPOSE: To explain the concepts that radiation oncologists need to understand to
      manage patients with juvenile nasopharyngeal angiofibroma (JNA). To accomplish
      this goal we first describe our institution's experience with radiotherapy for
      JNA and then use this data set as a framework for explaining the role of
      radiotherapy in the treatment of this uncommon tumor. METHODS AND MATERIALS: We
      studied the outcomes of all 24 patients treated with radiotherapy for JNA at our
      institution. All patients had at least 4 years of follow-up (median follow-up, 18
      years). The standard dose in the first half of the series was 30 Gy in 22
      treatments (1.43 Gy/treatment). After observing recurrences with this schedule,
      the prescription was changed to 35 to 36 Gy at 1.8 Gy/treatment. In all cases,
      the target volume was the primary site without an attempt to cover the regional
      nodes. RESULTS: All recurrences were at the primary site and presented within 5
      years of completing radiotherapy. There appeared to be a dose response for tumor
      control: 77% with 30 to 32 Gy versus 91% with 35 to 36 Gy. All recurrences
      following radiotherapy were successfully salvaged with surgery. The only
      complications from radiotherapy were cataracts in 2 patients. No patient had a
      significant growth abnormality or second tumor. CONCLUSIONS: Surgery is the best
      treatment for JNA when cure is likely with low morbidity, but the threshold for
      using radiotherapy should be low because moderate-dose radiotherapy cures about
      90% of patients with a low risk of serious complications. We recommend 36 Gy at
      1.8 Gy per treatment in most cases. Elective nodal irradiation is not necessary.
      Radiographic response should be almost complete within a year of radiotherapy.
      Patients should be followed with cross-sectional imaging every 6 months for at
      least 5 years.

PMID- 24674006
TI  - Treatment of hemoptysis associated with aspergilloma using external beam
      radiotherapy: A case report and literature review.

PMID- 24674007
TI  - The role of positron emission tomography for non-small cell lung cancer.
AB  - Lung cancer is the second most common cancer and the leading cause of cancer
      related deaths. 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) positron emission
      tomography (PET) fused with computed tomography (CT) has become the standard of
      care in the initial staging of patients with non-small cell lung cancer and has
      been increasingly utilized for radiation treatment planning as disease extent and
      tumor volumes are better defined than CT alone. The biologic information from FDG
      PET may be used for predicting outcome, assessing treatment response, and
      surveillance imaging. Addition of respiratory gating to PET reduces motion
      artifacts to improve tumor delineation. Novel radiotracers are being investigated
      to provide further biological information such as tumor hypoxia and cell
      proliferation. 

PMID- 24674008
TI  - In reply:.

PMID- 24674009
TI  - In reply:.

PMID- 24674010
TI  - Contouring the prostate bed.

PMID- 24674011
TI  - An empirical study of healthcare providers and patients' perceptions of
      electronic health records.
AB  - This paper is the result of a legal and policy analysis of a statistical poll
      focused on the area of Livorno conducted by the LIDER-Lab of the Scuola Superiore
      Sant'Anna (Pisa, Italy). Information were gathered by submitting questionnaires
      to both healthcare providers and their patients. The scope was to evaluate the
      interest engendered by the application of technology on health data processing
      along with the needs, expectations and concerns of patients and healthcare
      providers. The paper leads to the main policy proposals of increasing financial
      investments in e-health (or at least preserve this area from the generalized
      budget constraints public health is suffering nowadays) and introducing
      incentives to use computers for general practitioners.

PMID- 24674012
TI  - Mating systems and selection efficacy: a test using chloroplastic sequence data
      in Angiosperms.
AB  - Selfing is assumed to reduce selection efficacy, especially purifying selection.
      This can be tested using molecular data, for example by comparing the Dn/Ds ratio
      between selfing and outcrossing lineages. So far, little evidence of relaxed
      selection against weakly deleterious mutations (as inferred by a higher Dn/Ds
      ratio) in selfers as compared to outcrossers has been found, contrary to the
      pattern often observed between asexual and sexual lineages. However, few groups
      have been studied to date. To further test this hypothesis, we compiled and
      analysed chloroplastic sequence data sets in several plant groups. We found a
      general trend towards relaxed selection in selfers in our data sets but with weak
      statistical support. Simulations suggested that the results were compatible with
      weak-to-moderate Dn/Ds ratio differences in selfing lineages. Simple theoretical
      predictions also showed that the ability to detect relaxed selection in selfers
      could strongly depend on the distribution of the effects of deleterious mutations
      on fitness. Our results are compatible with a recent origin of selfing lineages
      whereby deleterious mutations potentially have a strong impact on population
      extinction or with a more ancient origin but without a marked effect of
      deleterious mutations on the extinction dynamics. 

PMID- 24674013
TI  - Impact of the lung oncology multidisciplinary team meetings on the management of
      patients with cancer.
AB  - AIMS: Multidisciplinary team (MDT) meetings are increasingly regarded as a
      component of multidisciplinary cancer care. We aimed to prospectively measure the
      impact of MDT meetings on clinicians' management plans for lung oncology
      patients, and the implementation rate of the meeting recommendations. METHODS:
      Consecutive patient cases presented at the weekly lung oncology MDT meetings were
      prospectively enrolled. Investigators compared the clinicians' management plans
      pre-meeting with the consensus plans post-meeting. The meeting was considered to
      have an impact on management plans if >=1 of the following changes were detected:
      tumor stage, histology, treatment intent or treatment modality, or if additional
      investigations were recommended. Investigators reviewed hospital patient records
      at 4 months to determine if the meeting recommendations were implemented. Reasons
      for non-implementation were also recorded. RESULTS: Of the 55 eligible cases, the
      MDT meeting changed management plans in 58% (CI 45-71%; P < 0.005). These changes
      included: additional investigations (59%), or changes in treatment modality
      (19%), treatment intent (9%), histology (6%) or tumor stage (6%). The meeting
      recommendations were implemented in 72% of cases. Reasons for non-implementation
      included deteriorating patient performance status, clinician's preference, the
      influence of new clinical information obtained after the meeting or patient
      decision. CONCLUSION: MDT meetings significantly impact on the management plans
      for lung oncology patients. The majority of MDT recommendations (72%) were
      implemented into patient care. These findings provide further evidence to support
      the role of MDT meetings as an essential part of the decision-making process for
      the optimal multidisciplinary management of patients with cancer.

PMID- 24674014
TI  - Construction and validation of a data collection tool for the clinical assessment
      of human responses of outpatients with chronic cardiovascular diseases.
AB  - PURPOSE: To develop and test the content validity of a nursing assessment tool
      for data collection (NATDC) based on NANDA-I for use in outpatients with chronic
      cardiovascular diseases. METHODS: Construction based on the literature,
      refinement with a pilot group of hypertensive outpatients and content validation
      by experts. FINDINGS: The NATDC questions were divided into demographic
      information of the patient and family, clinical data, physical examination, and
      interview according to NANDA-I domains. CONCLUSION: The NATDC was constructed and
      validated. IMPLICATIONS FOR NURSING PRACTICE: This tool can be used in patients
      with chronic illnesses who experience a variety of human responses seeking
      nursing care in an outpatient setting because it is based in human responses
      within a structured framework for nursing assessment.

PMID- 24674015
TI  - Local failure patterns for patients with nasopharyngeal carcinoma after intensity
      modulated radiotherapy.
AB  - BACKGROUND: To investigate the clinical feature and the local failure patterns
      after intensity-modulated radiotherapy for nasopharyngeal carcinoma. METHODS:
      Between March 2007 and July 2009, 710 patients with nasopharyngeal carcinoma were
      treated with intensity-modulated radiotherapy. The magnetic resonance imagings
      obtained at recurrence were registered with the original planning computed
      tomography for dosimetry analysis. RESULTS: With a median follow-up of 38 months,
      34 patients have developed local recurrence (32 cases valid). The incidence of
      invasion to nasopharynx, parapharyngeal space and the retropharyngeal space by
      the primary tumors was 100%, 75.0% and 62.5%, respectively, but 78.1%, 34.4% and
      21.9% at recurrence, respectively. The rate of invasion to ethmoid sinus was 3.1%
      by the primary tumors but 28.1% at recurrence (p=0.005). The topographic analysis
      of the local failure patterns showed "central" in 16 patients; "marginal" in 9;
      and "outside" in 7. The median volumes of primary gross tumor were 45.84 cm(3) in
      the central failure group, 29.44 cm(3) in the marginal failure group, and 21.52
      cm(3) in the outside failure group, respectively (p=0.012), and the median
      volumes of primary clinical target1 were 87.28 cm(3), 61.90 cm(3) and 58.74 cm(3)
      in the three groups, respectively (p=0.033). CONCLUSIONS: In patients with
      nasopharyngeal carcinoma treated with intensity-modulated radiotherapy, the
      recurrent tumors had their unique characteristic and regularity of invasion to
      adjacent structures. "Central" failure was the major local failure pattern. The
      volumes of primary gross tumor and clinical target1 were significantly correlated
      with recurrent patterns. Employ more aggressive approaches to tumor cells which
      will be insensitive to radiotherapy may be an effective way to reduce the central
      failure.

PMID- 24674016
TI  - Alfaxalone or ketamine-medetomidine in cats undergoing ovariohysterectomy: a
      comparison of intra-operative parameters and post-operative pain.
AB  - OBJECTIVE: To compare post-operative pain in cats after alfaxalone or ketamine-
      medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters
      during and after surgery. STUDY DESIGN: Prospective 'blinded' randomized clinical
      study. ANIMALS: Twenty-one healthy cats. METHODS: Cats were assigned randomly
      into two groups: Group A, anaesthesia was induced and maintained with alfaxalone
      [5 mg kg(-1) intravenously (IV) followed by boli (2 mg kg(-1) IV); Group MK,
      induction with ketamine (5 mg kg(-1) IV) after medetomidine (30 MUg kg(-1)
      intramuscularly (IM)], and maintenance with ketamine (2 mg kg(-1) IV). Meloxicam
      (0.2 mg kg(-1) IV) was administered after surgery. Basic physiological data were
      collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post
      operatively pain was assessed by three methods, a composite pain scale (CPS; 0-24
      points), a visual analogue scale (VAS 0-100 mm), and a mechanical wound threshold
      (MWT) device. Butorphanol (0.2 mg kg(-1) IM) was administered if CPS was scored
      >=13. Data were analyzed using a general linear model, Kruskal-Wallis analyses,
      Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant.
      Significance was set at p < 0.05. RESULTS: VASs were significantly higher at 0.5,
      1, 2, 4, and 20 hours in group A; MWT values were significantly higher at 8 and
      12 hours in group MK. Post-operative MWT decreased significantly compared to
      baseline in both groups. There was no difference in CPS at any time point. Five
      cats required rescue analgesia (four in A; one in MK). CONCLUSION AND CLINICAL
      RELEVANCE: Anaesthesia with ketamine-medetomidine was found to provide better
      post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary
      hyperalgesia developed in both groups. Alfaxalone is suitable for induction and
      maintenance of anaesthesia in cats undergoing OHE, but administration of
      additional sedative and analgesic drugs is highly recommended.

PMID- 24674017
TI  - Palmieri's double suture skin repair: a new double suture approach to cases of
      skin cancer and ulcerative lesions.
AB  - We describe two case reports to assess the efficacy of a new method suitable to
      close small-sized pressure ulcers and cancer-related skin lesions. 

PMID- 24674018
TI  - Unmasking masked hypertension.

PMID- 24674019
TI  - Evaluating perspectives for PRRS virus elimination from pig dense areas with a
      risk factor based herd index.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is wide-spread in pig
      populations globally. In many regions of Europe with intensive pig production and
      high herd densities, the virus is endemic and can cause disease and production
      losses. This fuels discussion about the feasibility and sustainability of virus
      elimination from larger geographic regions. The implementation of a program
      aiming at virus elimination for areas with high pig density is unprecedented and
      its potential success is unknown. The objective of this work was to approach pig
      population data with a simple method that could support assessing the feasibility
      of a sustainable regional PRRSV elimination. Based on known risk factors such as
      pig herd structure and neighborhood conditions, an index characterizing
      individual herds' potential for endemic virus circulation and reinfection was
      designed. This index was subsequently used to compare data of all pig herds in
      two regions with different pig- and herd-densities in Lower Saxony (North-West
      Germany) where PRRSV is endemic. Distribution of the indexed herds was displayed
      using GIS. Clusters of high herd index densities forming potential risk hot spots
      were identified which could represent key target areas for surveillance and
      biosecurity measures under a control program aimed at virus elimination. In an
      additional step, for the study region with the higher pig density (2463
      pigs/km(2) farmland), the potential distribution of PRRSV-free and non-free herds
      during the implementation of a national control program aiming at national virus
      elimination was modeled. Complex herd and trade network structures suggest that
      PRRSV elimination in regions with intensive pig farming like that of middle
      Europe would have to involve legal regulation and be accompanied by important
      trade and animal movement restrictions. The proposed methodology of risk index
      mapping could be adapted to areas varying in size, herd structure and density.
      Interpreted in the regional context, this could help to classify the density of
      risk and to accordingly target resources and measures for elimination. 

PMID- 24674020
TI  - Effect of birth weight and colostrum intake on mortality and performance of
      piglets after cross-fostering in sows of different parities.
AB  - The objective of this study was to evaluate the effect of colostrum intake on
      mortality and growth performance of piglets until 42 days of age, taking into
      account the birth weight, and parity order of sows. Colostrum intake from birth
      to 24h after birth was estimated in 300 piglets each from primiparous and
      multiparous sows. The piglets were cross-fostered in 25 primiparous and 25
      multiparous sows at 25.9+/-0.09 h after farrowing. The concentration of serum
      immunoglobulin G (IgG) was determined in the sows after the end of farrowing and
      in the piglets before cross-fostering (24h after farrowing), at 10 and 20 days of
      age. For high birth weight piglets (HBW - >1.3-1.7 kg) the probability of death
      was low regardless of their colostrum intake. Intermediate birth weight (IBW -
      >1.2-1.3 kg) and low birth weight (LBW - 1.1-1.2 kg) piglets had the same
      probability of death compared to HBW piglets, when colostrum intake reached 200
      and 250 g, respectively. The probability of low performance (<9.5 kg) was lower
      in HBW than in LBW and IBW piglets, regardless of colostrum intake. HBW piglets
      had higher weight at 14, 20, 28 and 42 days of age (P<0.05) than LBW piglets, and
      higher weight than IBW piglets at 28 and 42 days. Colostrum intake >250 g
      increased (P<0.05) the weight of piglets at 28 and 42 days of age, regardless of
      their birth weight. Piglets from primiparous biological dams consumed less
      colostrum (P<0.003) than piglets from multiparous dams, but their serum IgG
      concentrations at 24h after birth and their performance were similar (P>0.05).
      Piglets suckled by primiparous foster sows showed lower weight (P<0.05) at 20, 28
      and 42 days than piglets suckled by multiparous sows. Piglets that died before 42
      days of age had lower (P<0.05) birth weight, colostrum intake and serum IgG at 24
      h after birth compared to surviving piglets, and lower values were also observed
      in piglets with low performance compared to high (>9.5 kg) performance piglets.
      There were no differences in serum IgG concentrations at 10 and 20 days of age
      (P>0.05) between high and low performance piglets. In conclusion, both colostrum
      intake and birth weight are important for survival and growth of suckling
      piglets. LBW and IBW piglets are more dependent on colostrum intake than HBW
      piglets to assure higher survival and better development up to 42 days of age.
      Piglets suckled by multiparous sows have better development than those suckled by
      primiparous sows.

PMID- 24674021
TI  - Comparison of bacterial communities on limnic versus coastal marine particles
      reveals profound differences in colonization.
AB  - Marine and limnic particles are hotspots of organic matter mineralization
      significantly affecting biogeochemical element cycling. Fluorescence in-situ
      hybridization and pyrosequencing of 16S rRNA genes were combined to investigate
      bacterial diversity and community composition on limnic and coastal marine
      particles > 5 and > 10 MUm respectively. Limnic particles were more abundant
      (average: 1 * 10(7) l(-1)), smaller in size (average areas: 471 versus 2050
      MUm(2)) and more densely colonized (average densities: 7.3 versus 3.6 cells 100
      MUm(-2)) than marine ones. Limnic particle-associated (PA) bacteria harboured
      Alphaproteobacteria and Betaproteobacteria, and unlike previously suggested
      sizeable populations of Gammaproteobacteria, Actinobacteria and Bacteroidetes.
      Marine particles were colonized by Planctomycetes and Betaproteobacteria
      additionally to Alphaproteobacteria, Bacteroidetes and Gammaproteobacteria. Large
      differences in individual particle colonization could be detected. High
      throughput sequencing revealed a significant overlap of PA and free-living (FL)
      bacteria highlighting an underestimated connectivity between both fractions. PA
      bacteria were in 14/21 cases more diverse than FL bacteria, reflecting a high
      heterogeneity in the particle microenvironment. We propose that a ratio of Chao 1
      indices of PA/FL < 1 indicates the presence of rather homogeneously colonized
      particles. The identification of different bacterial families enriched on either
      limnic or marine particles demonstrates that, despite the seemingly similar
      ecological niches, PA communities of both environments differ substantially.

PMID- 24674022
TI  - X-ray structure of a novel endolysin encoded by episomal phage phiSM101 of
      Clostridium perfringens.
AB  - Gram-positive bacteria possess a thick cell wall composed of a mesh polymer of
      peptidoglycans, which provides physical protection. Endolysins encoded by phages
      infecting bacteria can hydrolyse peptidoglycans in the bacterial cell wall,
      killing the host bacteria immediately. The endolysin (Psm) encoded by episomal
      phage phiSM101 of enterotoxigenic Clostridium perfringens type A strain SM101
      exhibits potent lytic activity towards most strains of Clostridium perfringens.
      Psm has an N-terminal catalytic domain highly homologous to N-acetylmuramidases
      belonging to the glycoside hydrolase 25 family, and C-terminal tandem repeated
      bacterial Src homology 3 (SH3_3) domains as the cell wall-binding domain. The X
      ray structure of full-length Psm and a catalytic domain of Psm in complex with N
      acetylglucosamine were determined to elucidate the catalytic reaction and cell
      wall recognition mechanisms of Psm. The results showed that Psm may have adopted
      a neighbouring-group mechanism for the catalytic hydrolysing reaction in which
      the N-acetyl carbonyl group of the substrate was involved in the formation of an
      oxazolinium ion intermediate. Based on structural comparisons with other
      endolysins and a modelling study, we proposed that tandem repeated SH3_3 domains
      of Psm recognized the peptide side-chains of peptidoglycans to assist the
      catalytic domain hydrolysing the glycan backbone. 

PMID- 24674024
TI  - Risk factors for colonization with extended-spectrum beta-lactamase-producing
      enterobacteriaceae on admission to rehabilitation centres.
AB  - Patients newly admitted to rehabilitation centres are at high risk of
      colonization with multidrug-resistant bacteria because many of them have
      experienced prolonged stays in other healthcare settings and have had high
      exposure to antibiotics. We conducted a prospective study to determine the
      prevalence of and risk factors for colonization with extended-spectrum beta
      lactamase-producing Enterobacteriaceae (ESBL-PE) in this population. Subjects
      were screened by rectal swab for ESBL-PE within 2 days of admission. Swabs were
      plated on chromagar ESBL plates and the presence of ESBL was verified by a
      central laboratory. A multilevel mixed effects model was used to identify risk
      factors for ESBL-PE colonization. Of 2873 patients screened, 748 (26.0%) were
      positive for ESBL-PE. The variables identified as independently associated with
      ESBL-PE colonization were: recent stay in an acute-care hospital for over 2 weeks
      (OR=1.34; 95% CI, 1.12, 1.6), history of colonization with ESBL-PE (OR=2.97; 95%
      CI, 1.99, 4.43), unconsciousness on admission (OR=2.59; 95% CI, 1.55, 4.34),
      surgery or invasive procedure in the past year (OR=1.49; 95% CI, 1.2, 1.86) and
      antibiotic treatment in the past month (OR=1.80; 95% CI, 1.45, 2.22). The
      predictive accuracy of the model was low (area under the ROC curve 0.656). These
      results indicate that ESBL-PE colonization is common upon admission to
      rehabilitation centres. Some risk factors for ESBL-PE colonization are similar to
      those described previously; however, newly identified factors may be specific to
      rehabilitation populations. The high prevalence and low ability to stratify by
      risk factors may guide infection control and empirical treatment strategies in
      rehabilitation settings.

PMID- 24674025
TI  - Study of the fluid flow characteristics in a porous medium for CO2 geological
      storage using MRI.
AB  - The objective of this study was to understand fluid flow in porous media.
      Understanding of fluid flow process in porous media is important for the
      geological storage of CO2. The high-resolution magnetic resonance imaging (MRI)
      technique was used to measure fluid flow in a porous medium (glass beads BZ-02).
      First, the permeability was obtained from velocity images. Next, CO2-water
      immiscible displacement experiments using different flow rates were investigated.
      Three stages were obtained from the MR intensity plot. With increasing CO2 flow
      rate, a relatively uniform CO2 distribution and a uniform CO2 front were
      observed. Subsequently, the final water saturation decreased. Using core analysis
      methods, the CO2 velocities were obtained during the CO2-water immiscible
      displacement process, which were applied to evaluate the capillary dispersion
      rate, viscous dominated fractional flow, and gravity flow function. The capillary
      dispersion rate dominated the effects of capillary, which was largest at water
      saturations of 0.5 and 0.6. The viscous-dominant fractional flow function varied
      with the saturation of water. The gravity fractional flow reached peak values at
      the saturation of 0.6. The gravity forces played a positive role in the downward
      displacements because they thus tended to stabilize the displacement process,
      thereby producing increased breakthrough times and correspondingly high
      recoveries. Finally, the relative permeability was also reconstructed. The study
      provides useful data regarding the transport processes in the geological storage
      of CO2.

PMID- 24674027
TI  - Exploring the prevalence of skin tears and skin properties related to skin tears
      in elderly patients at a long-term medical facility in Japan.
AB  - The identification of appropriate skin tear prevention guidelines for the elderly
      requires clinicians to focus on local risk factors such as structural alterations
      of the epidermis and dermis related to skin tears. The aim of this cross
      sectional study is to explore the prevalence of skin tears and to explore skin
      properties related to skin tears in elderly Japanese patients at a long-term
      medical facility. After doing the prevalence study, 18 participants with skin
      tears and 18 without were recruited and an evaluation of their skin properties
      using 20-MHz ultrasonography, skin blotting and also Corneometer CM-825, Skin-pH
      meterPH905, VapoMeter, Moisture Meter-D and CutometerMPA580 was undertaken. A
      total of 410 patients were examined, the median age was 87 years and 73.2% were
      women. The prevalence of skin tears was 3.9%, and 50% of skin tears occurred on
      the dorsal forearm. The changes in skin properties associated with skin tears
      included increased low-echogenic pixels (LEP) by 20-MHz ultrasonography,
      decreased type IV collagen and matrix metalloproteinase-2, and increased tumour
      necrosis factor-alpha by skin blotting. In conclusion, this study suggests that
      increased dermal LEP, including solar elastosis, may represent a risk factor for
      skin tears; this indicates that skin tear risk factors might not only represent
      chronological ageing but also photoageing. 

PMID- 24674028
TI  - Darwin-Wallace Demons: survival of the fastest in populations of duckweeds and
      the evolutionary history of an enigmatic group of angiosperms.
AB  - In evolutionary biology, the term 'Darwinian fitness' refers to the lifetime
      reproductive success of an individual within a population of conspecifics. The
      idea of a 'Darwinian Demon' emerged from this concept and is defined here as an
      organism that commences reproduction almost immediately after birth, has a
      maximum fitness, and lives forever. It has been argued that duckweeds (sub-family
      Lemnoideae, order Alismatales), a group containing five genera and 34 species of
      small aquatic monocotyledonous plants with a reduced body plan, can be
      interpreted as examples of 'Darwinian Demons'. Here we focus on the species
      Spirodela polyrhiza (Great duckweed) and show that these miniaturised aquatic
      angiosperms display features that fit the definition of the hypothetical organism
      that we will call a 'Darwin-Wallace Demon' in recognition of the duel proponents
      of evolution by natural selection. A quantitative analysis (log-log bivariate
      plot of annual growth in dry biomass versus standing dry body mass of various
      green algae and land plants) revealed that duckweeds are thus far the most
      rapidly growing angiosperms in proportion to their body mass. In light of this
      finding, we discuss the disposable soma and metabolic optimising theories,
      summarise evidence for and against the proposition that the Lemnoideae (family
      Araceae) reflect an example of reductive evolution, and argue that, under real
      world conditions (environmental constraints and other limitations), 'Darwin
      Wallace Demons' cannot exist, although the concept remains useful in much the
      same way that the Hardy-Weinberg law does.

PMID- 24674026
TI  - DNA methylation subgroups and the CpG island methylator phenotype in gastric
      cancer: a comprehensive profiling approach.
AB  - BACKGROUND: Methylation-induced silencing of promoter CpG islands in tumor
      suppressor genes plays an important role in human carcinogenesis. In colorectal
      cancer, the CpG island methylator phenotype (CIMP) is defined as widespread and
      elevated levels of DNA methylation and CIMP+ tumors have distinctive
      clinicopathological and molecular features. In contrast, the existence of a
      comparable CIMP subtype in gastric cancer (GC) has not been clearly established.
      To further investigate this issue, in the present study we performed
      comprehensive DNA methylation profiling of a well-characterised series of primary
      GC. METHODS: The methylation status of 1,421 autosomal CpG sites located within
      768 cancer-related genes was investigated using the Illumina GoldenGate
      Methylation Panel I assay on DNA extracted from 60 gastric tumors and matched
      tumor-adjacent gastric tissue pairs. Methylation data was analysed using a
      recursively partitioned mixture model and investigated for associations with
      clinicopathological and molecular features including age, Helicobacter pylori
      status, tumor site, patient survival, microsatellite instability and BRAF and
      KRAS mutations. RESULTS: A total of 147 genes were differentially methylated
      between tumor and matched tumor-adjacent gastric tissue, with HOXA5 and hedgehog
      signalling being the top-ranked gene and signalling pathway, respectively.
      Unsupervised clustering of methylation data revealed the existence of 6 subgroups
      under two main clusters, referred to as L (low methylation; 28% of cases) and H
      (high methylation; 72%). Female patients were over-represented in the H tumor
      group compared to L group (36% vs 6%; P = 0.024), however no other significant
      differences in clinicopathological or molecular features were apparent. CpG sites
      that were hypermethylated in group H were more frequently located in CpG islands
      and marked for polycomb occupancy. CONCLUSIONS: High-throughput methylation
      analysis implicates genes involved in embryonic development and hedgehog
      signaling in gastric tumorigenesis. GC is comprised of two major methylation
      subtypes, with the highly methylated group showing some features consistent with
      a CpG island methylator phenotype.

PMID- 24674029
TI  - The reliability of WorkWell Systems Functional Capacity Evaluation: a systematic
      review.
AB  - BACKGROUND: Functional capacity evaluation (FCE) determines a person's ability to
      perform work-related tasks and is a major component of the rehabilitation
      process. The WorkWell Systems (WWS) FCE (formerly known as Isernhagen Work
      Systems FCE) is currently the most commonly used FCE tool in German
      rehabilitation centres. Our systematic review investigated the inter-rater, intra
      rater and test-retest reliability of the WWS FCE. METHODS: We performed a
      systematic literature search of studies on the reliability of the WWS FCE and
      extracted item-specific measures of inter-rater, intra-rater and test-retest
      reliability from the identified studies. Intraclass correlation coefficients >=
      0.75, percentages of agreement >= 80%, and kappa coefficients >= 0.60 were
      categorised as acceptable, otherwise they were considered non-acceptable. The
      extracted values were summarised for the five performance categories of the WWS
      FCE, and the results were classified as either consistent or inconsistent.
      RESULTS: From 11 identified studies, 150 item-specific reliability measures were
      extracted. 89% of the extracted inter-rater reliability measures, all of the
      intra-rater reliability measures and 96% of the test-retest reliability measures
      of the weight handling and strength tests had an acceptable level of reliability,
      compared to only 67% of the test-retest reliability measures of the
      posture/mobility tests and 56% of the test-retest reliability measures of the
      locomotion tests. Both of the extracted test-retest reliability measures of the
      balance test were acceptable. CONCLUSIONS: Weight handling and strength tests
      were found to have consistently acceptable reliability. Further research is
      needed to explore the reliability of the other tests as inconsistent findings or
      a lack of data prevented definitive conclusions.

PMID- 24674030
TI  - Editor's Note.

PMID- 24674031
TI  - Developing a national radiation oncology registry: From acorns to oaks.
AB  - PURPOSE: The National Radiation Oncology Registry (NROR) is a collaborative
      initiative of the Radiation Oncology Institute and the American Society of
      Radiation Oncology, with input and guidance from other major stakeholders in
      oncology. The overarching mission of the NROR is to improve the care of cancer
      patients by capturing reliable information on treatment delivery and health
      outcomes. METHODS: The NROR will collect patient-specific radiotherapy data
      electronically to allow for rapid comparison of the many competing treatment
      modalities and account for effectiveness, outcome, utilization, quality, safety,
      and cost. It will provide benchmark data and quality improvement tools for
      individual practitioners. The NROR steering committee has determined that
      prostate cancer provides an appropriate model to test the concept and the data
      capturing software in a limited number of sites. The NROR pilot project will
      begin with this disease-gathering treatment and outcomes data from a limited
      number of treatment sites across the range of practice; once feasibility is
      proven, it will scale up to more sites and diseases. RESULTS: When the NROR is
      fully implemented, all radiotherapy facilities, along with their radiation
      oncologists, will be solicited to participate in it. With the broader
      participation of the radiation oncology community, NROR has the potential to
      serve as a resource for determining national patterns of care, gaps in treatment
      quality, comparative effectiveness, and hypothesis generation to identify new
      linkages between therapeutic processes and outcomes. CONCLUSIONS: The NROR will
      benefit radiation oncologists and other care providers, payors, vendors, policy
      makers, and, most importantly, cancer patients by capturing reliable information
      on population-based radiation treatment delivery.

PMID- 24674032
TI  - Implementation of a "No Fly" safety culture in a multicenter radiation medicine
      department.
AB  - PURPOSE: The safe delivery of radiation therapy requires multiple disciplines and
      interactions to perform flawlessly for each patient. Because treatment is
      individualized and every aspect of the patient's care is unique, it is difficult
      to regiment a delivery process that works flawlessly. The purpose of this study
      is to describe one safety-directed component of our quality program called the
      "No Fly Policy" (NFP). METHODS AND MATERIALS: Our quality assurance program for
      radiation therapy reviewed the entire process of care prior, during, and after a
      patient's treatment course. Each component of care was broken down and rebuilt
      within a matrix of multidisciplinary safety quality checklists (QCL). The QCL
      process map was subsequently streamlined with revised task due dates and stopping
      rules. The NFP was introduced to place a holding pattern on treatment initiation
      pending reconciliation of associated stopping events. The NFP was introduced in a
      pilot phase using a Six-Sigma process improvement approach. Quantitative analysis
      on the performance of the new QCLs was performed using crystal reports in the
      Oncology Information Systems. Root cause analysis was conducted. RESULTS: Notable
      improvements in QCL performance were observed. The variances among staff in
      completing tasks reduced by a factor of at least 3, suggesting better process
      control. Steady improvements over time indicated an increasingly compliant and
      controlled adoption of the new safety-oriented process map. Stopping events led
      to rescheduling treatments with average and maximum delays of 2 and 4 days,
      respectively, with no reported adverse effects. The majority of stopping events
      were due to incomplete plan approvals stemming from treatment planning delays.
      Whereas these may have previously solicited last-minute interventions, including
      intensity modulated radiation therapy quality assurance, the NFP enabled
      nonpunitive, reasonable schedule adjustments to mitigate compromises in safe
      delivery. CONCLUSIONS: Implementation of the NFP has helped to mitigate risk from
      expedited care, convert reactive to proactive delays, and created a checklist,
      process driven, and variance-reducing culture in a large, multicenter department.

PMID- 24674023
TI  - Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in
      HIV-1 co-infected patients.
AB  - The growing number of cases of acute hepatitis C (AHC) infections among human
      immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in
      the last 10 years has promoted the search for predictors of AHC clearance as well
      as for epidemiological networks of viral transmission. We characterized the
      diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC
      patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18
      MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient
      samples with AHC were also investigated. An average of 39 clones from each sample
      was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the
      most abundant) from each quasispecies was also assayed for mitochondrial
      antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified
      two clusters of patients with highly related viruses, suggesting a common source
      of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously
      cleared HCV, although 78% of the treated patients achieved a sustained
      virological response after early treatment with pegylated interferon (pegIFN)
      plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a
      marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men
      with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from
      AHC patients also exhibited higher catalytic efficiency compared to CHC patients
      (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A
      protease catalytic efficiencies from AHC HIV-coinfected patients were compared
      with AHC monoinfected patients. The presence of epidemiological networks of HCV
      transmission was confirmed among HIV-1-positive MSM. In addition, substantial
      genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving
      MAVS may be associated with virus transmission and response to pegIFN/RBV
      treatment.

PMID- 24674033
TI  - Evaluation of a metal artifact reduction technique in tonsillar cancer
      delineation.
AB  - PURPOSE: Metal artifacts can degrade computed tomographic (CT) simulation imaging
      and impair accurate delineation of tumors for radiation treatment planning
      purposes. We investigated a Digital Imaging and Communications in Medicine-based
      metal artifact reduction technique in tonsillar cancer delineation. METHODS AND
      MATERIALS: Eight patients with significant artifact and tonsil cancer were
      evaluated. Each patient had a positron emission tomography (PET)-CT and a
      contrast-enhanced CT obtained at the same setting during radiotherapy simulation.
      The CTs were corrected for artifact using the metal deletion technique (MDT). Two
      radiation oncologists independently delineated primary gross tumor volumes (GTVs)
      for each patient on native (CTnonMDT), metal corrected (CTMDT), and reference
      standard (CTPET/nonMDT) imaging, 1 week apart. Mixed effects models were used to
      determine if differences among GTVs were statistically significant. Two
      diagnostic radiologists and 2 radiation oncologists independently qualitatively
      evaluated CTs for each patient. Ratings were on an ordinal scale from -3 to +3,
      denoting that CTMDT was markedly, moderately, or slightly worse or better than
      CTnonMDT. Scores were compared with a Wilcoxon signed-rank test. RESULTS: The
      GTVPET/nonMDT were significantly smaller than GTVnonMDT (P = .004) and trended to
      be smaller than GTVMDT (P = .084). The GTVnonMDT and GTVMDT were not
      significantly different (P = .93). There was no significant difference in the
      extent to which GTVnonMDT or GTVMDT encompassed GTVPET/nonMDT (P = .33). In the
      subjective assessment of image quality, CTMDT did not significantly outperform
      CTnonMDT. In the majority of cases, the observer rated the CTMDT equivalent to
      (53%) or slightly superior (41%) to the corresponding CTnonMDT. CONCLUSIONS: The
      MTD modified images did not produce GTVMDT that more closely reproduced
      GTVPET/nonMDT than did GTVnonMDT. Moreover, the MTD modified images were not
      judged to be significantly superior when compared to the uncorrected images in
      terms of subjective ability to visualize the tonsilar tumors. This study failed
      to demonstrate value of the adjunctive use of a CT corrected for artifacts in the
      tumor delineation process. Artifacts do make tumor delineation challenging, and
      further investigation of other body sites is warranted.

PMID- 24674034
TI  - Intensity modulated radiation therapy planning for patients with a metal hip
      prosthesis based on class solutions.
AB  - PURPOSE: With the aging of the population, an increasing number of patients with
      metallic hip implants are referred for radiotherapy treatment. Class solutions
      for intensity modulated radiation therapy (IMRT) treatment planning are generally
      not applicable for these patients due to the required avoidance of dose delivery
      through prostheses. In this work a new approach for IMRT planning is presented,
      allowing the use of a default beam setup. METHODS AND MATERIALS: For IMRT
      planning, Monaco (Elekta; CMS Software, Maryland Heights, MO) was used. In
      addition to the target and organs at risk, so-called prosthesis avoidance volumes
      (PAVs) were delineated in the beam's eye view projection for beams in which the
      prosthesis was partially in front of the target. By putting strict constraints on
      these virtual organs at risk, entrance dose delivery through a prosthesis is
      avoided while exit dose delivery is allowed. In this way, uncertainties in the
      dose delivery to the target and organs at risk, as derived by the treatment
      planning system, are largely minimized. To show the advantages of this IMRT-PAV
      technique, for 2 prostate cancer patients, 1 with bilateral and the other with
      unilateral metallic hip prostheses, obtained IMRT plans were compared with
      conventional IMRT plans using a prosthesis-avoiding beam setup. RESULTS: For both
      IMRT techniques a similar planning target volume coverage was achieved, but with
      the IMRT-PAV technique the mean doses to the bladder and the rectum were reduced
      by up to 25%. While the IMRT-PAV technique required more time for delineation,
      the time for treatment planning reduced because the default beam setup could be
      applied. The number of segments needed for dose delivery was comparable for both
      techniques. CONCLUSIONS: With the new IMRT-PAV technique IMRT class solutions can
      safely be applied for cancer patients with metallic hip prostheses, generally
      yielding a reduced dose delivery to organs at risk or improved target coverage.

PMID- 24674035
TI  - Improving cardiac dosimetry: Alternative beam arrangements for intensity
      modulated radiation therapy planning in patients with carcinoma of the distal
      esophagus.
AB  - PURPOSE: Radiation for carcinoma of the distal esophagus is associated with
      cardiac perfusion deficits and pericardial effusion. We performed a dosimetric
      analysis of alternative beam arrangements for use in intensity modulated
      radiation therapy (IMRT) planning, seeking to lower radiation dose to the heart.
      METHODS AND MATERIALS: Treatment plans using 4 separate beam arrangements were
      generated and optimized for 12 patients. Hemispheric and butterfly beam
      arrangements were compared with plans with posterior and lateral beam entries.
      Radiotherapy was planned to 50.4 Gy in 28 fractions, using step and shoot IMRT
      with 6 MV photons. Mean heart dose and volumes of heart and lung receiving up to
      specified doses (V5-V40) were recorded. Isodose distributions were evaluated for
      target coverage and normal tissue exposure. RESULTS: IMRT plans utilizing
      posterior-lateral beam arrangements significantly reduced mean cardiac doses
      (32.5 +/- 3.9 Gy, 33.3 +/- 3.2 Gy vs 24.3 +/- 3.7 Gy, and 23.4 +/- 4.2 Gy, P <
      .05, paired Student t test with post hoc Bonferroni correction) as well as the
      total heart volumes receiving at least 20 and 30 Gy. IMRT allowed the maximum
      cord dose to be limited to less than 40 Gy. While both posterior-lateral beam
      arrangements lead to improved cardiac dosimetry, mean lung doses as well as V5
      and V20 were slightly higher, although within accepted limits. Target coverage,
      homogeneity, and conformality were similar or improved with the use of
      alternative beam configurations. CONCLUSIONS: The use of IMRT with posterior
      lateral beams can significantly reduce radiation dose to cardiac structures with
      minimal increased dose to the lung. Future studies will assess the physiologic
      and clinical impact of cardiac sparing.

PMID- 24674036
TI  - Analysis of suitable prescribed isodose line fitting to planning target volume in
      stereotactic body radiotherapy using dynamic conformal multiple arc therapy.
AB  - PURPOSE: To assess the most suitable value of a relative prescribed dose in
      clinical treatment plans of stereotactic body radiotherapy (SBRT) using dynamic
      conformal multiple arc therapy to treat lung tumors. METHODS AND MATERIALS: We
      retrospectively generated alternative SBRT plans for typical examples of 8
      patients who had been treated with SBRT for a lung tumor with a prescribed dose
      of 50 Gy in 5 fractions. The prescribed dose had been defined as 80% of the
      maximal dose in the planning target volume (PTV) ("the 80% isodose plan").
      Alternative 20%-90% isodose plans at 10% intervals were generated (64 plans; 8
      plans for each of the 8 patients), and factors related to leaf margins, target
      volume, normal lung volume, and monitor units were compared using dose-volume
      histogram analysis. RESULTS: We could generate all the 64 plans. Compared with
      the 80% isodose plan, the V20 and mean lung dose (MLD) were both lower in the 60%
      plan; the V20 was approximately 19% lower (4.72% vs 3.84%) and the MLD was 13%
      lower (4.0 Gy vs 3.5 Gy). Mean PTV and ITV doses were higher in the lower
      percentage isodose plans. Compared with the 80% isodose plan, in the 60% isodose
      plan the mean PTV was 19% higher (56.1 Gy vs 66.8 Gy) and the mean ITV was 30%
      higher (59.6 Gy vs 77.4 Gy). The mean total monitor units increased more steeply
      than did the mean homogeneity index. The mean conformity index values in the 60%
      and 70% isodose plans were less than 1.15. CONCLUSIONS: The 60% isodose plan was
      considered the best plan in this analysis because of the lower comparative
      dosimetric factors in normal lung tissue (including V20 and MLD) and the higher
      comparative mean PTV and internal target volume doses achieved, along with good
      conformity index values. In clinical use, accurate estimation and commissioning
      should be performed for the dose distribution prior to selecting a plan. Further
      investigation is warranted to determine whether the calculated dosimetric
      advantages result in improved outcomes.

PMID- 24674038
TI  - Primary radiotherapy for locally advanced skin cancer near the eye.

PMID- 24674037
TI  - Initial clinical experience with a frameless and maskless stereotactic
      radiosurgery treatment.
AB  - PURPOSE: To evaluate the initial clinical experience with a frameless and
      maskless technique for stereotactic radiosurgery using minimal patient
      immobilization and real-time patient motion monitoring during treatment. We focus
      on the evaluation of the patient treatment process. METHODS AND MATERIALS: The
      study considered the first 23 patients treated with this technique. Head
      positioning was achieved with a patient-specific head mold made out of expandable
      foam that conforms to the patient's head. The face of the patient is left open
      for maximal comfort and so that motion of a region of interest consisting of the
      forehead, nose, eyes, and temporal bones can be monitored during treatment using
      a video surface imaging system (VisionRT Inc, London, UK). Initial setup of the
      patient was performed with the surface imaging system using the surface of the
      patient obtained from the treatment planning computed tomographic (CT) scan. The
      initial setup was confirmed and finalized with cone-beam CT (CBCT) prior to
      treatment. The shifts for final setup based on the CBCT and the duration of all
      the steps in the treatment process were recorded. Patients were monitored during
      treatment with surface imaging, and a beam hold-off was initiated when the
      patient's motion exceeded a prespecified tolerance. RESULTS: The average total
      setup time including surface imaging and CBCT was 26 minutes, while the portion
      corresponding to surface imaging was 14 minutes. The average treatment time from
      when the patient was placed on the treatment table until the last treatment beam
      was 40 minutes. Eight (35%) patients needed repositioning during the treatment.
      The average shifts identified from CBCT after initial setup with surface imaging
      were 1.85 mm in the anterior-posterior direction, and less than 1.0 mm in the
      lateral and superior-inferior directions. The longest treatment times (including
      beam hold-offs) happened for patients who fell asleep on the treatment table and
      were moving involuntarily. CONCLUSIONS: The frameless and maskless treatment
      using minimal immobilization and surface imaging has proven to be reasonably fast
      for routine clinical use. We observed that patient compliance is important. An
      additional degree of semi-rigid immobilization would be helpful for patients who
      fall asleep and involuntarily move during the procedure.

PMID- 24674039
TI  - Efficacy of coronary artery screening tests and intervention in hemodialysis
      patients.
AB  - Although cardiovascular disease (CVD) is an important cause of death in patients
      on hemodialysis, evidence of a beneficial effect of percutaneous intervention
      (PCI) on stable heart disease is scarce. We investigated the cardiovascular
      outcomes of hemodialysis patients under our policy of encouraging coronary artery
      screening tests to the extent possible. A total of 147 hemodialysis patients have
      been treated in our clinic so far. In 98 of them, coronary artery screening tests
      were performed, three in unstable and 95 in asymptomatic patients. Significant
      coronary artery stenosis was detected in 29 at the first tests and in 11 during
      subsequent tests (40/98, 40.8%), and PCI or coronary artery bypass grafting
      (CABG) was performed. Multiple PCIs were needed in 21 patients. In the other 49
      patients, coronary artery screening tests were not undertaken based on the
      nephrologist's decision or patient refusal. At the end of the study, 73 (74.5%)
      patients with tests, and 14 (28.6%) without tests were still outpatients (P <
      0.01). Of 40 patients transferred to other hospitals for medical reasons or who
      died before transfer, there was cerebrovascular accident in eight, malignancy in
      six, congestive heart failure without CVD in four, infection in three, sudden
      cardiac death in one, and others 18. No patient with tests died of CVD and the
      only patient who died of sudden cardiac death probably due to myocardial
      infarction was a patient who had declined the screening tests. Coronary artery
      screening tests, intervention and subsequent periodic tests for asymptomatic
      hemodialysis patients can reduce the occurrence of cardiovascular events in this
      population.

PMID- 24674040
TI  - Validation of the Quality of Diagnoses, Interventions, and Outcomes (Q-DIO)
      instrument for use in Brazil and the United States.
AB  - PURPOSE: To assess the reliability and validity of Quality of Diagnoses,
      Interventions, and Outcomes (Q-DIO) in Brazil and in the United States. METHODS:
      The sample comprised 180 records: centers 1 (electronic records and standardized
      language) and 2 (paper-based records without standardized language in Brazil, and
      center 3 (electronic records without standardized language) in the United States.
      Reliability and discriminant construct validity was analyzed. FINDINGS:
      Cronbach's alpha for all 29 Q-DIO items were greater than or equal to 0.70 for
      all centers; construct validity was significantly different between the three
      study centers. CONCLUSIONS: These results indicate that Q-DIO is valid and
      reliable for assessing the quality of nursing records. IMPLICATIONS FOR NURSING
      PRACTICE: The Q-DIO may be useful to assess the quality and accuracy of nursing
      records.

PMID- 24674042
TI  - Routine counseling about intrauterine contraception for women seeking emergency
      contraception.
AB  - OBJECTIVE: To compare contraceptive knowledge and use among women seeking
      emergency contraception (EC) before and after an inner-city clinic began
      providing structured counseling and offering same-day intrauterine device (IUD)
      or implant placement to all women seeking EC. STUDY DESIGN: For 8 months before
      and 21 months after this change in clinic policy, women aged 15-45 who wanted to
      avoid pregnancy for at least 6 months were asked to complete surveys immediately,
      3 and 12 months after their clinic visit. In addition, we abstracted electronic
      medical record (EMR) data on all women who sought EC (n=328) during this period.
      We used chi-squared tests to assess pre/post differences in survey and EMR data.
      RESULTS: Surveys were completed by 186 women. After the clinic began offering
      structured counseling, more women had accurate knowledge of the effectiveness of
      IUDs, immediately and 3 months after their clinic visit. In addition, more women
      initiated IUD or implant use (survey: 40% vs. 17% preintervention, p=0.04; EMR:
      22% vs. 10% preintervention, p=0.01), and fewer had no contraceptive use (survey:
      3% vs. 17% preintervention, p<0.01; EMR: 32% vs. 68%, p<0.01) in the 3 months
      after seeking EC. EMR data indicate that when same-day placement was offered,
      11.0% of women received a same-day IUD. Of those who received a same-day IUD, 88%
      (23/26) reported IUD use at 3-months and 80% (12/15) at 12 months. CONCLUSIONS:
      Routine provision of structured counseling with the offer of same-day IUD
      placement increases knowledge and use of IUDs 3 months after women seek EC.
      IMPLICATIONS: Women seeking EC from family planning clinics should be offered
      counseling about highly effective reversible contraceptives with the option of
      same-day contraceptive placement.

PMID- 24674041
TI  - Effect of progestins on immunity: medroxyprogesterone but not norethisterone or
      levonorgestrel suppresses the function of T cells and pDCs.
AB  - OBJECTIVES: The potential effect of hormonal contraception on HIV-1 acquisition
      and transmission represents an important public health issue. Several
      observational studies have suggested an association between the use of hormonal
      contraception, in particular injectable depot medroxyprogesterone acetate (DMPA),
      and an increased risk of HIV-1 acquisition and transmission. We and others have
      previously demonstrated that DMPA acts as a potent inhibitor of innate and
      adaptive immune mechanisms. The study presented here addresses the
      immunomodulatory properties of several common progestins with a potential to
      replace DMPA. STUDY DESIGN: To identify safe alternatives to DMPA, we tested the
      effect of commonly used progestins on the function of human primary T cells and
      plasmacytoid dendritic cells (pDCs) obtained from the blood of healthy
      premenopausal women. RESULTS: Medroxyprogesterone acetate (MPA) inhibited the
      activation of T cells and pDCs in response to T cell receptor- and Toll-like
      receptor-mediated activation at physiological concentrations. Etonogestrel
      exerted a partial suppressive activity at high concentrations. In sharp contrast,
      norethisterone (NET) and levonorgestrel (LNG) did not exhibit detectable
      immunosuppressive activity. CONCLUSION: Evidence indicating the immunosuppressive
      properties of DMPA strongly suggests that DMPA should be discontinued and
      replaced with other forms of long-term contraception. Since NET and LNG do not
      exert immunosuppressive properties at physiological concentrations, these
      progestins should be considered as alternative contraceptives for women at high
      risk for HIV-1 infection. IMPLICATIONS: The presented data suggest that, at
      physiological levels, the progestins NET and LNG do not suppress cytokine
      production by immune cells and should be considered as alternatives to DMPA;
      however, more in vivo testing is needed to confirm this data.

PMID- 24674052
TI  - Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumors: a
      meta-analysis.
AB  - BACKGROUND: The postulated relationship between KIT/PDGFRA mutations and their
      prognostic value in gastrointestinal stromal tumors (GISTs) has generated intense
      attention during the past decade, despite the fact that a great deal of studies
      have been conducted on this subject. To provide a strong quantitative estimate of
      this postulated relationship, we carried out a meta-analysis which combined,
      compared, and summarized the results of existing relevant studies. METHODS:
      Studies were identified by searching databases and reviewing citations in
      relevant articles. Of 48 potentially relevant studies, we combined individual
      patient data from 18 studies which involved 1,487 patients with GISTs, by which
      we made a comparison between the positive KIT mutation subgroup and the negative
      KIT mutation subgroup (PDGFRA mutation and wild type). We tabulated and analyzed
      the patient characteristics from each study, including general information such
      as age and gender, histopathological parameters, and clinical follow-up outcomes.
      RESULTS: KIT mutations, compared with PDGFRA mutations and wild type, showed a
      marked increased risk not only for tumor size (>5 cm) but also for higher mitotic
      activity (>5), suggesting that KIT mutations significantly correlated with the
      National Comprehensive Cancer Network (NCCN) high risk or National Institutes of
      Health (NIH) high risk (1.74 (95% CI, 1.20 to 2.53) and 2.00 (95% CI, 1.08 to
      3.68), respectively). Moreover, higher recurrence and metastasis was observed in
      GISTs with KIT mutations, revealing its closer correlation with clinical
      malignant risk (P<0.001 for each, with odds ratio (OR) of 2.06 (95%, 1.37 to
      3.11) and 2.77 (95%, 1.64 to 4.67), respectively). High risk or malignant GISTs
      with KIT mutations had a significantly poorer prognosis, as measured by 3-year
      overall survival, compared to those with PDGFRA mutations and wild type (0.47
      (95% CI, 0.25 to 0.90)). CONCLUSIONS: KIT mutations, compared with PDGFRA
      mutations and wild type, represent a poorer prognostic marker in high risk or
      malignant GISTs.

PMID- 24674053
TI  - The cardiopulmonary effects of a peripheral alpha-2-adrenoceptor antagonist, MK
      467, in dogs sedated with a combination of medetomidine and butorphanol.
AB  - OBJECTIVE: To compare the cardiopulmonary effects of intravenous (IV) and
      intramuscular (IM) medetomidine and butorphanol with or without MK-467. STUDY
      DESIGN: Prospective, randomized experimental cross-over. ANIMALS: Eight purpose
      bred beagles (two females, six males), 3-4 years old and weighing 14.5 +/-1.6 kg
      (mean +/- SD). METHODS: All dogs received four different treatments as follows:
      medetomidine 20 MUg kg(-1) and butorphanol tartrate 0.1 mg kg(-1) IV and IM (MB),
      and MB combined with MK-467,500 MUg kg(-1) (MBMK) IV and IM. Heart rate (HR),
      arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac
      output, respiratory rate (fR ), rectal temperature (RT) were measured and
      arterial blood samples were obtained for gas analysis at baseline and at 3, 10,
      20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI),
      systemic vascular resistance index (SVRI) and oxygen delivery index (DO2 I) were
      calculated. After the follow-up period atipamezole 50 MUg kg(-1) IM was given to
      reverse sedation. RESULTS: HR, CI and DO2 I were significantly higher with MBMK
      after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT
      were significantly lower after MBMK than with MB. There were no differences in fR
      between treatments, but arterial partial pressure of oxygen decreased transiently
      after all treatments. Recoveries were uneventful following atipamezole
      administration after all treatments. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467
      attenuated the cardiovascular effects of a medetomidine-butorphanol combination
      after IV and IM administration.

PMID- 24674054
TI  - Exaggerated blood pressure response to exercise is not associated with masked
      hypertension in patients with high normal blood pressure levels.
AB  - The association between exaggerated blood pressure (BP) response to exercise
      (ExBPR) and "masked hypertension" is unclear. Medical records of patients with
      high-normal BP who were evaluated in the Chaim Sheba Screening Institute Ramat
      Gan, Israel, during the years 2002-2007 and referred for 24-hour ambulatory BP
      monitoring (ABPM) and exercise test were reviewed. Data on exercise tests
      performed in the preceding 5 years were retrieved. Reproducible ExBPR was defined
      when it was recorded at least twice. BP levels on 24-hour ABPM were compared
      between patients with a normal BP response and those with an ExBPR (systolic BP
      >=200 mm Hg). Sixty-nine normotensive patients with high normal BP levels were
      identified. ExBPR was recorded in 43 patients and was reproducible in 28. BP
      levels on 24-hour ABPM were similar in patients with and without ExBPR. In
      patients with high-normal BP levels, ExBPR is not associated with masked
      hypertension. 

PMID- 24674055
TI  - Chorismate-dependent transcriptional regulation of quinate/shikimate utilization
      genes by LysR-type transcriptional regulator QsuR in Corynebacterium glutamicum:
      carbon flow control at metabolic branch point.
AB  - The qsu operon of Corynebacterium glutamicum comprises four genes (qsuABCD) that
      underpin the microorganism's quinate/shikimate utilization pathways. The genes
      encode enzymes that catalyse reactions at the metabolic branch point between the
      biosynthesis route for synthesis of aromatic compounds and the catabolic route
      for degradation of quinate and shikimate for energy production. A qsuR gene
      located immediately upstream of qsuA encodes a protein (QsuR) which activates the
      operon in the presence of quinate or shikimate. Three observations support
      chorismate, an intermediate of the biosynthesis route, as a direct effector of
      QsuR: First, induction of qsuA mRNA in the presence of either quinate or
      shikimate disappears upon deletion of the gene encoding chorismate synthase.
      Second, chorismate accumulates when the operon is induced. Third, a DNase I
      protected segment by QsuR is shortened in the presence of chorismate. The QsuR
      tetramer senses the accumulation of chorismate and activates qsu genes that
      promote the quinate/shikimate catabolic instead of the aromatic compounds
      biosynthetic route. Such chorismate-dependent control of carbon flow has not been
      previously described. 

PMID- 24674056
TI  - Trends and changes in Clostridium difficile diagnostic policies and their impact
      on the proportion of positive samples: a national survey.
AB  - In June 2012, Israeli guidelines for laboratories were published defining the
      recommended methods for diagnosis of Clostridium difficile infection (CDI). We
      conducted this survey to examine the effects of the new recommendations on the
      proportions of rejected and positive samples by the different methods. A survey
      was mailed to the directors of all general hospital (GH) and health maintenance
      organization (HMO) clinical microbiology laboratories. The report was divided
      into two periods, before and after implementation of the guidelines. Surveys were
      completed by 13/28 GH laboratories and 5/6 HMO laboratories. All 18 of these
      laboratories used C. difficile toxin (CDT) enzyme immunoassay alone during the
      first period of the survey. In the second period, nine laboratories (Group A)
      used CDT-PCR: two of them used this method exclusively while the other seven used
      it to resolve most (>90%) of the discrepant results (glutamate dehydrogenase
      antigen (GDH) +/CDT-]. The other nine laboratories (Group B) used combined
      GDH/CDT assay, using CDT PCR in only a minority (<20%) of GDH+/CDT- cases. The
      overall proportion of rejected samples increased from 9.5% in the first period to
      13.9% in the second (p<0.001). Between the first and second periods the
      proportion of positive samples increased from 9.0% to 11.6% in group A
      laboratories (p<0.001), but decreased from 12.9% to 9.7% in group B laboratories
      (p<0.001). Implementation of the guidelines has resulted in a significant
      increase in the proportion of rejected samples and in the proportion testing
      positive, suggesting more appropriate test utilization and improved sensitivity
      in the laboratory diagnosis of CDI.

PMID- 24674058
TI  - TCA precipitation.
AB  - Trichloroacetic acid (TCA) precipitation of proteins is commonly used to
      concentrate protein samples or remove contaminants, including salts and
      detergents, prior to downstream applications such as SDS-PAGE or 2D-gels. TCA
      precipitation denatures the protein, so it should not be used if the protein must
      remain in its folded state (e.g., if you want to measure a biochemical activity
      of the protein). 

PMID- 24674059
TI  - Coimmunoprecipitation of proteins from yeast.
AB  - This protocol outlines a procedure for testing whether two proteins interact. A
      target protein will be immunoprecipitated using an antibody that recognizes it
      (or a tagged version of the protein). The immunoprecipitated material will be
      separated by SDS-PAGE and analyzed by Western blotting to assess the presence of
      a candidate interacting protein(s). 

PMID- 24674060
TI  - Coupling antibody to cyanogen bromide-activated sepharose.
AB  - Antibodies will be immobilized on a cyanogen bromide-activated Sepharose for
      subsequent use in pull-down assays or immunoaffinity purification.

PMID- 24674057
TI  - Current concept of abdominal sepsis: WSES position paper.
AB  - Although sepsis is a systemic process, the pathophysiological cascade of events
      may vary from region to region.Abdominal sepsis represents the host's systemic
      inflammatory response to bacterial peritonitis.It is associated with significant
      morbidity and mortality rates, and is the second most common cause of sepsis
      related mortality in the intensive care unit.The review focuses on sepsis in the
      specific setting of severe peritonitis. 

PMID- 24674061
TI  - Analysis of protein-protein interactions by coimmunoprecipitation.
AB  - Proteins generally act by binding to other molecules, including proteins. When
      proteins bind to other proteins, we speak of protein-protein interactions. It has
      become apparent that protein-protein interactions are critically important to
      many processes that take place in the cell, including signal transduction,
      regulation of gene expression, vesicular transport, nuclear import and export,
      and cell migration (Pawson and Nash, 2003). This has led to the recognition of
      protein-protein interactions as targets for drug development and to an increased
      interest in the identification of novel protein-protein interactions (Fry and
      Vassilev, 2005; Fry, 2006; Tord et al., 2007). Coimmunoprecipitation is a
      technique that is used to confirm novel protein-protein interactions in the
      context of a living cell or organism. In addition, coimmunoprecipitation is also
      used to study the dynamics of protein-protein interactions in response to intra-
      or extracellular stimuli, or can be used to study the effect of mutations on the
      ability of a protein to engage its binding partner. In a coimmunoprecipitation
      experiment, a protein of interest is isolated by immunoprecipitation.
      Subsequently, the presence of binding partners can be assessed by immunoblotting
      (see Western Blotting using Chemiluminescent Substrates).

PMID- 24674062
TI  - Use and application of hydrophobic interaction chromatography for protein
      purification.
AB  - The objective of this section is to provide the reader with guidelines and
      background on the use and experimental application of Hydrophobic Interaction
      chromatography (HIC) for the purification of proteins. The section will give step
      by step instructions on how to use HIC in the laboratory to purify proteins.
      General guidelines and relevant background information is also provided. 

PMID- 24674063
TI  - Hydroxyapatite chromatography: purification strategies for recombinant proteins.
AB  - The purpose of this section is to provide developmental purification strategies
      for recombinant proteins on a column of hydroxyapatite and then to optimize them
      for repeated purification cycles using effect additives. Surface neutralization
      solutions (SNS) (patent pending) and/or the addition of calcium ions reduce the
      solubility of hydroxyapatite thus extending the column lifetime. This section
      leads the user through purification protocol screening followed by SNS--calcium
      ion supplementation step gradients for purifying a monoclonal antibody from its
      contaminants. The section provides simple analytical tools using a 160 ml scale
      column to predict column life at the process scale. However, the development
      engineer is encouraged to test the model in a minimum-sized process column.

PMID- 24674064
TI  - Salting out of proteins using ammonium sulfate precipitation.
AB  - Protein solubility is affected by ions. At low ion concentrations (<0.5 M),
      protein solubility increases along with ionic strength. Ions in the solution
      shield protein molecules from the charge of other protein molecules in what is
      known as 'salting-in'. At a very high ionic strength, protein solubility
      decreases as ionic strength increases in the process known as 'salting-out'.
      Thus, salting out can be used to separate proteins based on their solubility in
      the presence of a high concentration of salt. In this protocol, ammonium sulfate
      will be added incrementally to an E. coli cell lysate to isolate a recombinantly
      over-expressed protein of 20 kDa containing no cysteine residues or tags.

PMID- 24674065
TI  - Using ion exchange chromatography to purify a recombinantly expressed protein.
AB  - Ion exchange chromatography (IEX) separates molecules by their surface charge, a
      property that can vary vastly between different proteins. There are two types of
      IEX, cation exhange and anion exchange chromatography. The protocol that follows
      was designed by the authors for anion exchange chromatography of a recombinantly
      expressed protein having a pI of 4.9 and containing two cysteine residues and one
      tryptophan residue, using an FPLC system. Prior to anion exchange, the protein
      had been salted out using ammonium sulfate precipitation and partially purified
      via hydrophobic interaction chromatography (see Salting out of proteins using
      ammonium sulfate precipitation and Use and Application of Hydrophobic Interaction
      Chromatography for Protein Purification). Slight modifications to this protocol
      may be made to accommodate both the protein of interest and the availability of
      equipment.

PMID- 24674066
TI  - Gel filtration chromatography (size exclusion chromatography) of proteins.
AB  - The protocol described here allows the student to construct a standard curve for
      a gel filtration column with a separation range of 5-250 kD. The size
      (hydrodynamic radius) of a protein species stable in a buffer containing Tris
      HCl, NaCl, and DTT is determined using this column. Modifications may be made to
      the buffer to accommodate the protein of interest and the separation range of the
      column.

PMID- 24674067
TI  - Expression and purification of membrane proteins.
AB  - Approximately 30% of a genome encodes for membrane proteins. They are one of the
      most important classes of proteins in that they can receive, differentiate, and
      transmit intra- and intercellular signals. Some examples of classes of membrane
      proteins include cell-adhesion molecules, translocases, and receptors in
      signaling pathways. Defects in membrane proteins may be involved in a number of
      serious disorders such as neurodegenerative diseases (e.g., Alzheimer's) and
      diabetes. Furthermore, membrane proteins provide natural entry and anchoring
      points for the molecular agents of infectious diseases. Thus, membrane proteins
      constitute ~50% of known and novel drug targets. Progress in this area is slowed
      by the requirement to develop methods and procedures for expression and isolation
      that are tailored to characteristic properties of membrane proteins. A set of
      standard protocols for the isolation of the targets in quantities that allow for
      the characterization of their individual properties for further optimization is
      required. The standard protocols given below represent a workable starting point.
      If optimization of yields is desired, a variation of conditions as outlined in
      the theory section is recommended.

PMID- 24674068
TI  - Explanatory chapter: choosing the right detergent.
AB  - If working with membrane proteins, practically all biochemical techniques can be
      used as for soluble proteins, the important point being that detergents must be
      added to keep the membrane proteins in solution. This protocol is meant to help
      in choosing the right detergent for a given application. 

PMID- 24674069
TI  - One-dimensional SDS-polyacrylamide gel electrophoresis (1D SDS-PAGE).
AB  - This protocol describes a denaturing polyacrylamide gel system utilizing sodium
      dodecyl sulfate (SDS) to separate protein molecules based on size as first
      described by Laemmli (1970). SDS-PAGE can be used to monitor protein
      purifications, check the purity of samples, and to estimate molecular weights for
      unknown proteins. 

PMID- 24674070
TI  - Coomassie blue staining.
AB  - This protocol describes Coomassie brilliant blue staining, one of the most common
      methods of detecting proteins in polyacrylamide gels (PAGE). 

PMID- 24674071
TI  - Silver staining of SDS-polyacrylamide gel.
AB  - To detect nanogram quantities of protein and nucleic acids on SDS-PAGE gels. 

PMID- 24674072
TI  - Standard in vitro assays for protein-nucleic acid interactions--gel shift assays
      for RNA and DNA binding.
AB  - The characterization of protein-nucleic acid interactions is necessary for the
      study of a wide variety of biological processes. One straightforward and widely
      used approach to this problem is the electrophoretic mobility shift assay (EMSA),
      in which the binding of a nucleic acid to one or more proteins changes its
      mobility through a nondenaturing gel matrix. Usually, the mobility of the nucleic
      acid is reduced, but examples of increased mobility do exist. This type of assay
      can be used to investigate the affinity of the interaction between the protein
      and nucleic acid, the specificity of the interaction, the minimal binding site,
      and the kinetics of the interaction. One particular advantage of EMSA is the
      ability to analyze multiple proteins, or protein complexes, binding to nucleic
      acids. This assay is relatively quick and easy and utilizes equipment available
      in most laboratories; however, there are many variables that can only be
      determined empirically; therefore, optimization is necessary and can be highly
      dependent upon the system. The protocol described here is for the poly(A)-binding
      protein (PABP) binding to an unstructured RNA probe of 43 bases. While this may
      be a useful protocol for some additional assays, it is recommended that both
      reaction conditions and gel running conditions be tailored to the individual
      interaction to be probed. 

PMID- 24674073
TI  - Protein filter binding.
AB  - This protocol describes a method to monitor the binding of nucleic acid to
      protein, allowing the determination of the apparent affinity of a nucleic acid
      protein interaction. 

PMID- 24674075
TI  - Explanatory chapter: troubleshooting protein expression: what to do when the
      protein is not soluble.
AB  - Production of soluble protein remains a bottleneck in the biochemistry and
      structural biology fields. Unfortunately, there is no 'magic bullet' that solves
      all solubility problems. The following is a protocol to test whether a protein
      expressed recombinantly is soluble, and possible strategies to circumvent
      insolubility issues. 

PMID- 24674074
TI  - Explanatory chapter: troubleshooting recombinant protein expression: general.
AB  - One of the most daunting problems for biochemists is the expression of
      recombinant proteins. Often, the host organism differs from the organism from
      which the gene coding for the protein of interest was derived. This article
      provides guidelines to determine whether or not protein expression is a problem,
      describes possible reasons for low protein expression, and covers several
      possible solutions. A protocol for measuring protein expression during E. coli
      cell growth and after induction is given. The reader should note that low protein
      expression is a complex problem that often stems from a variety of factors.
      Combinations of the solutions presented in this article may be required to solve
      a problem of protein expression. A brief overview of host cell expression systems
      is given, but the article primarily focuses on expression in E. coli as this is
      the most commonly used host organism. Some of the methods discussed here,
      however, may be applied to other expression systems. 

PMID- 24674076
TI  - Western blotting using chemiluminescent substrates.
AB  - Western blotting is a powerful and commonly used tool to identify and quantify a
      specific protein in a complex mixture (Towbin et al., 1979). The technique
      enables indirect detection of protein samples immobilized on a nitrocellulose or
      polyvinylidene fluoride (PVDF) membrane. 

PMID- 24674078
TI  - Disturbed subsurface microbial communities follow equivalent trajectories despite
      different structural starting points.
AB  - Microbial community structure, and niche and neutral processes can all influence
      response to disturbance. Here, we provide experimental evidence for niche versus
      neutral and founding community effects during a bioremediation-related organic
      carbon disturbance. Subsurface sediment, partitioned into 22 flow-through
      columns, was stimulated in situ by the addition of acetate as a carbon and
      electron donor source. This drove the system into a new transient biogeochemical
      state characterized by iron reduction and enriched Desulfuromonadales,
      Comamonadaceae and Bacteroidetes lineages. After approximately 1 month conditions
      favoured sulfate reduction, and were accompanied by a substantial increase in the
      relative abundance of Desulfobulbus, Desulfosporosinus, Desulfitobacterium and
      Desulfotomaculum. Two subsets of four to five columns each were switched from
      acetate to lactate amendment during either iron (earlier) or sulfate (later)
      reduction. Hence, subsets had significantly different founding communities. All
      lactate treatments exhibited lower relative abundances of Desulfotomaculum and
      Bacteroidetes, enrichments of Clostridiales and Psychrosinus species, and a
      temporal succession from highly abundant Clostridium sensu stricto to
      Psychrosinus. Regardless of starting point, lactate-switch communities followed
      comparable structural trajectories, whereby convergence was evident 9 to 16 days
      after each switch, and significant after 29 to 34 days of lactate addition.
      Results imply that neither the founding community nor neutral processes
      influenced succession following perturbation.

PMID- 24674079
TI  - Advanced light microscopy.

PMID- 24674080
TI  - Prenatal effects of retinoic acid on lumbar spinal cord development and liver
      antioxidants in rats.
AB  - During embryonic and early postnatal development, retinoic acid (RA) regulates
      genes that control neuronal differentiation and neurite outgrowth from the neural
      tube. The effects of high levels of RA on the CNS can be detected via nitric
      oxide (NO), which plays a crucial role in neural transmission. The aim of the
      study was to investigate the prenatal influence of high levels of RA on postnatal
      development of nitrergic structures in lumbar spinal cord and antioxidant status.
      RA was administered orally at a dose of 10mg/kg body weight to pregnant female
      Wistar rats during days 8-10 of gestation. Neuronal nitric oxide synthase (nNOS)
      of lumbar spinal cord sections was processed for visualization via nicotinamide
      adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry on postnatal
      day one, day twenty-one and in adults. The results suggest that prenatal
      administration of high levels of RA is not associated with postnatal
      morphological changes in nNOS-positive neurons in the rat lumbar spinal cord. An
      estimation of the activity of enzymes related to the storage of retinoid in the
      liver showed possible side effects. Suppression and deepening of superoxide
      dismutase activity persisted into adulthood, and a concurrent downregulation of
      glutathione reductase was noted. A decrease in reduced glutathione persisted
      until adulthood when other compensatory mechanisms were probably active to
      maintain an appropriate level. 

PMID- 24674081
TI  - Knowledge, perceptions, and experiences of family caregivers and home care
      providers of physical restraint use with home-dwelling elders: a cross-sectional
      study in Japan.
AB  - BACKGROUND: The use of physical restraints by family caregivers with home
      dwelling elders has not been extensively studied but it might be widespread.
      Furthermore, it is also not clear how home care providers who support family
      caregivers perceive the use of physical restraint in elders' homes. This study
      assessed family caregivers' and home care providers' knowledge and perceptions of
      physical restraint used with elders living at home in Japan, a country with the
      highest proportion of elders in the world and where family caregiving is common.
      METHODS: We undertook a cross-sectional study of 494 family caregivers, 201 home
      helpers, 78 visiting nurses, 131 visiting physicians, and 158 care managers of
      home-dwelling frail elders needing some care and medical support in Japan, using
      questionnaires on knowledge of 11 physical restraint procedures prohibited in
      institutions and 10 harmful effects of physical restraints, perceptions of 17
      reasons for requiring physical restraints, and experiences involving physical
      restraint use. RESULTS: Family caregivers were aware of significantly fewer
      recognized prohibited physical restraint procedures and recognized harmful
      effects of physical restraint than home care providers, and differences among
      home care providers were significant. The average importance rating from 1
      (least) to 5 (most) of the 17 reasons for requiring physical restraints was
      significantly higher among family caregivers than home care providers, and
      significantly different among the home care providers. Moreover, these
      differences depended in part on participation in physical restraint education
      classes. While 20.1% of family caregivers had wavered over using physical
      restraints, 40.5% of home care providers had seen physical restraints used in
      elders' homes and 16.7% had advised physical restraint use or used physical
      restraints themselves. CONCLUSIONS: Knowledge and perceptions of physical
      restraints differed between family caregivers and home care providers and were
      also diverse among home care providers. Because both groups might be involved in
      physical restraint use with home-dwelling elders, home care providers should
      acquire standardized and appropriate knowledge and perceptions of physical
      restraints to help family caregivers minimize abusive physical restraint use.

PMID- 24674082
TI  - Anterior segment optical coherence tomography of live ocular cysticercosis.

PMID- 24674083
TI  - Pressure necrosis of the fingertip during management of hand burn injury: a word
      of caution.

PMID- 24674084
TI  - Six sigma tools for a patient safety-oriented, quality-checklist driven radiation
      medicine department.
AB  - INTRODUCTION: The purpose of this work was to develop and implement six sigma
      practices toward the enhancement of patient safety in an electronic, quality
      checklist-driven, multicenter, paperless radiation medicine department. METHODS
      AND MATERIALS: A quality checklist process map (QPM), stratified into
      consultation through treatment-completion stages was incorporated into an
      oncology information systems platform. A cross-functional quality management team
      conducted quality-function-deployment and define-measure-analyze-improve-control
      (DMAIC) six sigma exercises with a focus on patient safety. QPM procedures were
      Pareto-sorted in order of decreasing patient safety risk with failure mode and
      effects analysis (FMEA). Quantitative metrics for a grouped set of highest risk
      procedures were established. These included procedural delays, associated
      standard deviations and six sigma Z scores. Baseline performance of the QPM was
      established over the previous year of usage. Data-driven analysis led to
      simplification, standardization, and refinement of the QPM with standard
      deviation, slip-day reduction, and Z-score enhancement goals. A no-fly policy
      (NFP) for patient safety was introduced at the improve-control DMAIC phase, with
      a process map interlock imposed on treatment initiation in the event of FMEA
      identified high-risk tasks being delayed or not completed. The NFP was introduced
      in a pilot phase with specific stopping rules and the same metrics used for
      performance assessments. A custom root-cause analysis database was deployed to
      monitor patient safety events. RESULTS: Relative to the baseline period, average
      slip days and standard deviations for the risk-enhanced QPM procedures improved
      by over threefold factors in the NFP period. The Z scores improved by
      approximately 20%. A trend for proactive delays instead of reactive hard stops
      was observed with no adverse effects of the NFP. The number of computed potential
      no-fly delays per month dropped from 60 to 20 over a total of 520 cases. The
      fraction of computed potential no-fly cases that were delayed in NFP compliance
      rose from 28% to 45%. Proactive delays rose to 80% of all delayed cases. For
      potential no-fly cases, event reporting rose from 18% to 50%, while for actually
      delayed cases, event reporting rose from 65% to 100%. CONCLUSIONS: With complex
      technologies, resource-compromised staff, and pressures to hasten treatment
      initiation, the use of the six sigma driven process interlocks may mitigate
      potential patient safety risks as demonstrated in this study.

PMID- 24674085
TI  - Video surface image guidance for external beam partial breast irradiation.
AB  - OBJECTIVE: Accelerated partial breast irradiation is an emerging treatment option
      for early stage breast cancer. With accelerated partial breast irradiation,
      patient setup, and target registration accuracy is vital. The current study
      compared various methods for isocenter placement accuracy. METHODS AND MATERIALS:
      Twenty-three patients treated on an institutional-approved partial breast
      irradiation protocol were monitored at each treatment fraction. All patients
      included in this study underwent clip placement at the time of surgery. Patients
      underwent computed tomographic simulation and surface contours were used to
      reconstruct a reference surface map. At the treatment machine, patients were
      initially positioned by laser alignment to tattoos. Orthogonal kilovoltage
      imaging of the chest wall, followed by video surface mapping of the breast, was
      performed. This video surface map was matched to the reference surface map to
      adjust the couch position. Verification orthogonal chest wall imaging and video
      surface mapping was again performed. The accuracy of setup by laser, orthogonal
      imaging of the chest wall, and surface alignment was retrospectively compared
      using the centroid clip position as the reference standard. The impact of setup
      error by surface alignment and by orthogonal kilovoltage imaging on planning
      target volume coverage was then calculated. RESULTS: Laser-based positioning
      resulted in a residual setup error of 3.9 +/- 3.7 mm, 4.6 +/- 3.9 mm, and 4.3 +/-
      4.5 mm in the posterior-anterior (P-A), inferior-superior (I-S), and left-right
      (L-R) directions, respectively, using clips as the reference standard. Setup
      based on bony anatomy with orthogonal imaging resulted in residual setup error of
      3.2 +/- 2.9 (P-A), 4.2 +/- 3.5 (I-S), and 4.7 +/- 5.3 mm (L-R). Setup with video
      surface mapping resulted in a residual setup error of 1.9 +/- 2.2, 1.8 +/- 1.9,
      and 1.8 +/- 2.1 mm in the P-A, I-S, and L-R directions, respectively. Vector
      spatial deviation was 8.8 +/- 4.2, 8.3 +/- 3.8, and 4.0 +/- 2.3 mm with laser,
      chest wall on board imaging, and video surface mapping based setup, respectively.
      Setup by video surface mapping resulted in improved dosimetric coverage of the
      planning target volume when compared with orthogonal imaging of the chest wall
      (V100 96.0% +/- 0.1% vs 89.3% +/- 0.2%; V95 99.7% +/- 0.01% vs 98.6% +/- 0.01%, P
      < .05). CONCLUSIONS: Video surface mapping of the breast is a more accurate
      method for isocenter placement in comparison to conventional laser-based
      alignment or orthogonal kilovoltage imaging of the chest wall.

PMID- 24674086
TI  - Postmastectomy chest wall radiotherapy with single low-energy electron beam: An
      assessment of outcome and prognostic factors.
AB  - PURPOSE: This study aimed to evaluate the outcome of patients who had received
      postmastectomy chest wall radiotherapy using a single electron beam, and to
      identify the relevant factors that influenced prognosis. METHODS: The medical
      records of patients with breast cancer treated with postmastectomy radiotherapy
      from January 2000 to December 2004 were retrospectively analyzed (n = 328). Two
      hundred seventy-one (82.6%) patients were staged as (tumor-nodes-metastasis
      [TNM]) T3-4, any N, M0; or T1-2, N2-3, M0, and 57 (17.4%) patients were staged as
      T1-2, N1, M0. All patients received chest wall radiation with a 6-10 MeV electron
      beam. In addition, 327 patients (99.7%) received supraclavicular node radiation,
      67 (20.4%) axillary radiation, and 35 (10.7%) internal mammary chain (IMC)
      radiation. Chemotherapy with anthracycline and taxane was given to 323 patients
      (98.5%). Of patients with positive hormone receptor, 183 (82.8%) received hormone
      therapy and 8 patients with negative and 3 patients with unknown hormone receptor
      received hormone therapy. Locoregional recurrence (LRR), distant metastasis (DM),
      and overall survival (OS) were calculated using the Kaplan-Meier method, and the
      differences assessed by log-rank test. RESULTS: The median follow-up time was 78
      months (range, 5-123 months) for patients who remained alive. The 5-year LRR, DM,
      disease-free survival and OS rates were 5.9%, 26.2%, 72.5%, and 83.1%,
      respectively. LRR occurred in 1 or more sites in 21 patients. The 5-year
      recurrence rates in the chest wall, supraclavicular node, axilla, and internal
      mammary chain were 1.9%, 2.3%, 2.9%, and 0%, respectively. In multivariate
      analysis, hormone therapy was the only independent favorable prognostic factor
      for LRR (P = .017). LRR was significantly associated with DM and OS. The 5-year
      DM rate was 82.9% and 22.7% (P < .0001) and the 5-year OS rate was 52.8% and
      84.7% (P < .0001) for patients with or without LRR. The treatment-related
      toxicity was low, with the incidence of symptomatic pneumonitis being 0.3%.
      CONCLUSIONS: Breast cancer patients can be treated with postmastectomy single
      electron beam radiotherapy with excellent local control and low toxicity.

PMID- 24674087
TI  - Evaluation of variability in seroma delineation between clinical specialist
      radiation therapist and radiation oncologist for adjuvant breast irradiation.
AB  - PURPOSE: Breast cancer is managed by a multidisciplinary team with a goal for the
      timely provision of high quality care. Given radiation oncologist (RO) time
      constraints, an opportunity arises for task delegation of breast seroma target
      delineation to an advanced practice clinical specialist radiation therapist
      (CSRT) with clinical and technical expertise to facilitate treatment planning. To
      explore this further, we quantitatively evaluated the variability in post
      surgical seroma delineation between the CSRT and ROs. METHODS: Specialized site
      specific training was provided to the CSRT, who, with 7 ROs, independently
      contoured the seroma and graded its clarity, using the cavity visualization score
      (CVS), for 20 patients with clinical stage Tis-2N0 breast tumors. The conformity
      indices were analyzed for all possible pairs of delineations. The estimated
      "true" seroma contour was derived from the RO contours using the simultaneous
      truth and performance level estimation algorithm. Generalized kappa coefficient
      and center of mass metrics were used to examine the performance level of the CSRT
      in seroma delineations. RESULTS: The CVS of the CSRT correlated well with the
      mean RO-group CVS, (Spearman rho = 0.87, P < .05). The mean seroma conformity
      index for the RO group was 0.61 and 0.65 for the CSRT; a strong correlation was
      observed between the RO and CSRT conformity indices (Spearman rho = 0.95, P <
      .05). Almost perfect agreement levels were observed between the CSRT contours and
      the STAPLE RO consensus contours, with an overall kappa statistic of 0.81 (P <
      .0001). The average center of mass shift between the CSRT and RO consensus
      contour was 1.69 +/- 1.13 mm. CONCLUSIONS: Following specialized education and
      training, the CSRT delineated seroma targets clinically comparable with those of
      the radiation oncologists in women with early breast tumors suitable for
      accelerated partial breast or whole breast radiotherapy following lumpectomy.
      This study provides support for potential task delegation of breast seroma
      delineation to the CSRT in our current multidisciplinary environment. Further
      study is needed to assess the impact of this role expansion on radiotherapy
      system efficiency.

PMID- 24674088
TI  - Dosimetric evaluation of a "virtual" image-guidance alternative to explicit 6
      degree of freedom robotic couch correction.
AB  - PURPOSE: Clinical evaluation of a "virtual" methodology for providing 6 degrees
      of freedom (6DOF) patient set-up corrections and comparison to corrections
      facilitated by a 6DOF robotic couch. METHODS: A total of 55 weekly in-room image
      guidance computed tomographic (CT) scans were acquired using a CT-on-rails for 11
      pelvic and head and neck cancer patients treated at our facility. Fusion of the
      CT-of-the-day to the simulation CT allowed prototype virtual 6DOF correction
      software to calculate the translations, single couch yaw, and beam-specific
      gantry and collimator rotations necessary to effectively reproduce the same
      corrections as a 6DOF robotic couch. These corrections were then used to modify
      the original treatment plan beam geometry and this modified plan geometry was
      applied to the CT-of-the-day to evaluate the dosimetric effects of the virtual
      correction method. This virtual correction dosimetry was compared with calculated
      geometric and dosimetric results for an explicit 6DOF robotic couch correction
      methodology. RESULTS: A (2%, 2mm) gamma analysis comparing dose distributions
      created using the virtual corrections to those from explicit corrections showed
      that an average of 95.1% of all points had a gamma of 1 or less, with a standard
      deviation of 3.4%. For a total of 470 dosimetric metrics (ie, maximum and mean
      dose statistics for all relevant structures) compared for all 55 image-guidance
      sessions, the average dose difference for these metrics between the plans
      employing the virtual corrections and the explicit corrections was -0.12% with a
      standard deviation of 0.82%; 97.9% of all metrics were within 2%. CONCLUSIONS:
      Results showed that the virtual corrections yielded dosimetric distributions that
      were essentially equivalent to those obtained when 6DOF robotic corrections were
      used, and that always outperformed the most commonly employed clinical approach
      of 3 translations only. This suggests that for the patient datasets studied here,
      highly effective image-guidance corrections can be made without the use of a
      robotic couch.

PMID- 24674089
TI  - Efficacy of fiducial marker-based image-guided radiation therapy in prostate
      tomotherapy and potential dose coverage improvement using a patient positioning
      optimization method.
AB  - PURPOSE: To evaluate the dose coverage efficacy of fiducial marker-based prostate
      tomotherapy and a positioning correction optimization technique for the
      improvement of suboptimal dose distributions. METHODS: Three gold fiducial
      markers were implanted in prostate glands for patients who were to receive
      prostate tomotherapy. TomoTherapy megavoltage computed tomographies (MVCTs;
      TomoTherapy, Madison, WI) were routinely acquired at treatment and were
      registered to corresponding planning CTs based on the markers to correct for
      interfractional positioning deviations using translational table movements. The
      prostate glands and seminal vesicles were delineated on the MVCTs acquired for 10
      patients at different treatment fractions and the treatment dose coverage was
      computed with the marker-based correction taken into account. The treatment dose
      coverage was compared with the corresponding plan to evaluate the efficacy of the
      marker-based image-guided radiation therapy (IGRT) approach. Separately, a hill
      climbing optimization algorithm was used to optimize the positioning by
      maximizing a dose-based objective function. During the optimization, the dose was
      constantly recomputed with the translational correction until an optimized dose
      coverage was reached. This optimized dose coverage was compared with the marker
      based dose coverage to evaluate dosimetric improvement for treatments in which
      suboptimal dose distributions were observed after the marker-based corrections.
      RESULTS: Suboptimal dose coverage of prostate glands and seminal vesicles were
      observed in about 8 and 6 of a total 75 fractions, respectively, after the marker
      based IGRT positioning corrections. Six of the 10 patients experienced 1 or more
      factions of suboptimal prostate gland coverage and 2 of the 10 patients
      experienced 1 or more fractions of suboptimal seminal vesicle dose coverage.
      Utilization of the proposed positioning correction optimization method led to
      satisfactory dose coverage of both prostate glands and seminal vesicles for all
      10 patients. CONCLUSIONS: Given the planning target volume margin size specified
      in the current study, the fiducial marker-based IGRT approach may not be
      completely adequate to achieve desired dose coverage of the target volumes at
      every fraction. Due to relatively poor image quality of MVCTs, additional
      investigations may be required to confirm the finding. The proposed positioning
      correction optimization method is shown to effectively improve the observed
      suboptimal dose coverage of the target volumes.

PMID- 24674090
TI  - Radiation-induced sarcoma following radiation prophylaxis of heterotopic
      ossification.

PMID- 24674091
TI  - In regard to Vargo et al: "Early Clinical Outcomes for 3 Radiation Techniques for
      Brain Metastases: Focal Versus Whole-Brain".

PMID- 24674092
TI  - The IFITM5 mutation c.-14C > T results in an elongated transcript expressed in
      human bone; and causes varying phenotypic severity of osteogenesis imperfecta
      type V.
AB  - BACKGROUND: The genetic mutation resulting in osteogenesis imperfecta (OI) type V
      was recently characterised as a single point mutation (c.-14C > T) in the 5'
      untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with
      expression restricted to skeletal tissue. This mutation creates an alternative
      start codon and has been shown in a eukaryotic cell line to result in a longer
      variant of IFITM5, but its expression has not previously been demonstrated in
      bone from a patient with OI type V. METHODS: Sanger sequencing of the IFITM5 5'
      UTR was performed in our cohort of subjects with a clinical diagnosis of OI type
      V. Clinical data was collated from referring clinicians. RNA was extracted from a
      bone sample from one patient and Sanger sequenced to determine expression of wild
      type and mutant IFITM5. RESULTS: All nine subjects with OI type V were
      heterozygous for the c.-14C > T IFITM5 mutation. Clinically, there was
      heterogeneity in phenotype, particularly in the manifestation of bone fragility
      amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present
      in bone. CONCLUSIONS: The c.-14C > T IFITM5 mutation does not result in an RNA
      null allele but is expressed in bone. Individuals with identical mutations in
      IFITM5 have highly variable phenotypic expression, even within the same family.

PMID- 24674093
TI  - Co-colonization of vanA and vanB Enterococcus faecium of clonal complex 17 in a
      patient with bacteremia due to vanA E. faecium.
AB  - A 53-year-old Vietnamese man with liver cirrhosis was transferred from a
      Vietnamese hospital to our tertiary care hospital in Korea in order to undergo a
      liver transplantation. Bacteremia due to vanA Enterococcus faecium was diagnosed,
      and stool surveillance cultures for vancomycin-resistant enterococci (VRE) were
      positive for both vanA and vanB E. faecium. Pulsed-field gel electrophoresis
      analysis revealed that the 2 vanA VRE isolates from the blood and stool were
      clonal, but the vanB VRE was unrelated to the vanA VRE. vanA and vanB VRE were
      ST64 and ST18, single-allele variations of clonal complex 17, respectively. This
      is the first case report of vanA VRE bacteremia in a Vietnamese patient and
      demonstrates the reemergence of vanB VRE since a single outbreak occurred 15years
      ago in Korea. The reemergence of vanB VRE emphasizes the importance of VRE
      genotyping to prevent the spread of new VRE strains. 

PMID- 24674094
TI  - Mumps-associated meningitis and encephalitis in patients with no suspected mumps
      infection.
AB  - Mumps virus (MuV) was detected in the cerebrospinal fluid (CSF) of 6 of 158
      patients with meningitis or encephalitis in absence of clinical mumps in the
      context of mumps epidemics. Our results suggest the need for the study of MuV RNA
      in the CSF of neurological patients in this context. 

PMID- 24674095
TI  - Relationship between residual renal function and serum fibroblast growth factor
      23 in patients on peritoneal dialysis.
AB  - Fibroblast growth factor 23 (FGF23) levels in dialysis patients are influenced by
      various factors, including phosphorus load. However, the clinical parameters that
      determine serum FGF23 levels in patients on peritoneal dialysis (PD) remain
      unclear. The aim of the present study was to examine the effects of clinical
      factors, on serum FGF23 levels, with an emphasis on residual renal function
      (RRF). This cross-sectional study included 56 outpatients undergoing PD therapy.
      Urine volume >= 100 mL/day or renal creatinine (Cr) clearance was used as a
      surrogate marker for RRF. Clinical characteristics were compared between patients
      with and without RRF. Linear regression analysis was conducted with serum FGF23
      level as the dependent variable and renal Cr clearance as the main independent
      variable. The median and interquartile range of serum FGF23 levels were 5970
      (1451-11,688) pg/mL. Patients with RRF showed higher urinary and total phosphate
      eliminations, and lower serum FGF23 and phosphate levels than patients without
      RRF. Multivariate linear regression analysis showed that the renal Cr clearance
      and serum phosphate and dialysis history were negatively associated with serum
      FGF23 levels, even after adjusting for potential confounders including peritoneal
      Cr clearance. Further, the predictabilities of serum FGF23 were comparable among
      renal Cr clearance, Kt/V for urea, and renal phosphate clearance. RRF determined
      by renal Cr clearance or residual urine volume is an independent negative
      determinant of serum FGF23 levels in PD patients.

PMID- 24674096
TI  - The use of Nursing Interventions Classification (NIC) in identifying the workload
      of nursing: an integrative review.
AB  - PURPOSE: To synthesize evidence related to the use of the Nursing Interventions
      Classification in order to identify nursing workload. METHOD: An integrative
      literature review was conducted in June 2013. FINDINGS: The search strategy
      yielded a total of 111 references, 18 of which were retrieved, read, and
      evaluated for relevance. A set of 10 articles met the selection criteria.
      CONCLUSION: A review of papers regarding the Nursing Interventions Classification
      and workload revealed the following themes: the identification of nursing
      interventions in areas of expertise and estimated times for their completion, the
      distribution of interventions in direct and indirect care, and the prevalence of
      the type of care in a given healthcare setting.

PMID- 24674097
TI  - Determination of the minimum infusion rate (MIR) of alfaxalone required to
      prevent purposeful movement of the extremities in response to a standardised
      noxious stimulus in goats.
AB  - OBJECTIVE: To determine the minimum infusion rate (MIR) of alfaxalone required to
      prevent purposeful movement of the extremities in response to noxious
      stimulation. STUDY DESIGN: Prospective, experimental. ANIMALS: Eight healthy
      goats; four does and four wethers. METHODS: Anaesthesia was induced with
      alfaxalone 3 mg kg(-1) intravenously (IV). A continuous IV infusion of
      alfaxalone, initially at 0.2 mg kg(-1)  minute(-1) , was initiated. Following
      endotracheal intubation the goats breathed spontaneously via a circle breathing
      circuit delivering supplementary oxygen. The initial infusion rate was maintained
      for 30 minutes before testing for responses. The stimulus was clamping on the
      proximal (soft) part of one digit of the hoof with Vulsellum forceps for 60
      seconds. In the absence or presence of purposeful movement of the extremities,
      the infusion rate was reduced or increased by 0.02 mg kg(-1)  minute(-1) and held
      constant for 30 minutes before claw-clamping again. Alfaxalone MIR was calculated
      as the mean of the infusion rates that allowed and abolished movement. Cardio
      respiratory parameters were measured. Recovery from general anaesthesia was timed
      and quality scored. Results are presented as median (range). RESULTS: The MIR of
      alfaxalone was 0.16 (0.14-0.18) mg kg(-1)  minute(-1) or 9.6 (8.4-10.8) mg kg(-1)
      hour(-1) . Induction of and recovery from anaesthesia were excitement-free.
      Cardio-respiratory changes were minimal, although compared to baseline HR
      increased, and at 2 minutes post-induction, (prior to oxygen supplementation),
      PaO2 decreased significantly from 84 (80-88) to 70 (51-72) mmHg [11.2 (10.7-11.7)
      to 9.3 (6.8-9.6) kPa]. Sporadic muscle twitches, unrelated to depth of
      anaesthesia, were observed during the period of general anaesthesia. Time
      (minutes) to sternal recumbency and standing were 4.0 (3.0-10.0) and 41.5 (25.0
      57.0) respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone can be used
      for total intravenous anaesthesia (TIVA) in goats and is associated with minimal
      adverse effects. Oxygen supplementation is advised, especially when working at
      higher altitudes.

PMID- 24674098
TI  - Adaptive response in hepatitis B virus infection.
AB  - Hepatitis B virus (HBV) is a major cause of acute and chronic liver inflammation
      worldwide. The immune response against the virus represents a key factor in
      determining infection outcome, in terms of both viral clearance and the
      perpetuation of liver damage. Significant advances have recently been achieved
      regarding the functions of antiviral CD8+ T cells, leading to a better
      understanding of their abnormalities during chronic infection as well as the
      pathways to be manipulated to reverse the immune impairment of chronic infection.
      In this review, we aimed to analyse the patterns of adaptive immunity that
      develop during acute infection and the profiles in chronic infection. In addition
      to CD8+ T cells, which are the best-described subset to date, we reviewed and
      commented on the direct and indirect roles of CD4+ T cells and B cells. 

PMID- 24674099
TI  - A Partial Least Squares Analysis of the self reference effect in Alzheimer's
      disease: a reply to Irish.

PMID- 24674100
TI  - Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia
      -the results of a multicentre study.
AB  - Since the first carbapenem-resistant Klebsiella pneumoniae strain was isolated in
      2008, Enterobacteriaceae with reduced susceptibility to one or more carbapenems
      have emerged sporadically in different geographical regions in Croatia. These
      observations gave rise to a multicenter study on carbapenem resistance in
      Enterobacteriaceae from Croatia. Fifty-seven carbapenem-non-susceptible strains
      of Enterobacteriaceae were collected during 2011-2012 from four large hospital
      centres in Croatia. Overall, 36 strains produced VIM-1 beta-lactamase, three
      produced NDM-1, and one produced KPC-2. A high degree of clonal relatedness was
      observed in Enterobacter cloacae and Citrobacter freundii strains, in contrast to
      K. pneumoniae strains. BlaVIM genes were located within class1 integron which
      contained genes encoding resistance to aminoglycosides (aacA4 ). The study found
      strong association between blaVIM and qnrB6 and between blaNDM and qnrA6 genes. 

PMID- 24674101
TI  - Application of disability-adjusted life years to predict the burden of injuries
      and fatalities due to public exposure to engineering technologies.
AB  - BACKGROUND: As a public safety regulator, the Technical Standards and Safety
      Authority (TSSA) of Ontario, Canada predicts and measures the burden of injuries
      and fatalities as its primary means of characterizing the state of public safety
      and for decision-making purposes through the use of a simulation model. The paper
      proposes a simulation-based predictive model and the use of disability-adjusted
      life years (DALYs) as a population health metric for the purposes of reporting,
      benchmarking, public safety decision-making, and organizational goal setting. The
      proposed approach could be viewed as advancement in the application of
      traditional population health metrics, used primarily for public health policy
      decisions, for the measurement and prediction of safety risks across a wide
      variety of engineering technologies to which the general public is exposed.
      RESULTS: The proposed model is generic and applicable to a wide range of devices
      and technologies that are typically used by the general public. As an example, a
      measure of predicted risk that could result from the use of and exposure to
      elevating devices in the province of Ontario is presented in terms of the DALY
      metric. The predictions are further categorized in terms of the causal
      attribution of the risks for the purposes of identifying and focusing decision
      making efforts. The results are also presented by taking into consideration
      factors such as near-misses or precursor events as termed in certain industries.
      CONCLUSIONS: The ability to predict potential health impacts has three
      significant advantages for a public safety regulator - external reporting,
      decision-making to ensure public safety, and organizational benchmarking. The
      application of the well-known Monte Carlo simulation has been proposed to predict
      the health impacts expressed in terms of DALYs. The practicality of the proposed
      ideas has been demonstrated through the application of the prediction model to
      characterizing and managing risks associated with elevating devices in the
      province of Ontario, Canada.

PMID- 24674102
TI  - Long term use of metformin leading to vitamin B 12 deficiency.
AB  - Metformin is a commonly used oral hypoglycaemic agent worldwide. Gastrointestinal
      side effects and lactic acidosis related to metformin usage are commonly
      recognized. However, the associated vitamin B12 deficiency is less well known. We
      present a case of long term metformin use resulting in vitamin B12 deficiency. 

PMID- 24674103
TI  - Involvement of the Acr3 and DctA anti-porters in arsenite oxidation in
      Agrobacterium tumefaciens 5A.
AB  - Microbial arsenite (AsIII) oxidation forms a critical piece of the arsenic cycle
      in nature, though our understanding of how and why microorganisms oxidize AsIII
      remains rudimentary. Our model organism Agrobacterium tumefaciens 5A contains two
      distinct ars operons (ars1 and ars2) that are similar in their coding region
      content. The ars1 operon is located nearby the aio operon that is essential for
      AsIII oxidation. The AsIII/H(+) anti-porters encoded by acr3-1 and acr3-2 are
      required for maximal AsIII and antimonite (SbIII) resistance, but acr3-1
      (negatively regulated by ArsR-1) appears more active in this regard and also
      required for AsIII oxidation and expression of aioBA. A malate-phosphate anti
      porter DctA is regulated by RpoN and AsIII, and is required for normal growth
      with malate as a sole carbon source. Qualitatively, a DeltadctA mutant was normal
      for AsIII oxidation and AsIII/SbIII resistance at metalloid concentrations
      inhibitory to the Deltaacr3-1 mutant; however, aioBA induction kinetics was
      significantly phase-shift delayed. Acr3 involvement in AsIII/SbIII resistance is
      reasonably well understood, but the role of Acr3 and DctA anti-porters in AsIII
      oxidation and its regulation is unexpected, and suggests that controlled AsIII
      trafficking across the cytoplasmic membrane is important to a process understood
      to occur in the periplasm.

PMID- 24674104
TI  - Abstracts of the 2014 AAAAI Annual Meeting, February 28-March 4, 2014, San Diego,
      CA.

PMID- 24674106
TI  - Gastrostomy tube dislodgment acute pancreatitis.
AB  - Percutaneous gastrostomy is well established root for long term feeding of
      patients who cannot be fed orally. The risks of percutanous gastrostomy insertion
      are low. Tube related complications often resolved by placing a Foley catheter or
      other balloon gastrostomy tube as a temporary solution. Gastrostomy tube related
      gastric, duodenal and billiary obstruction were reported. Gastrostomy tube
      related pancreatitis is scarcely described. We described a patient who suffered a
      pancreatitis related to Foley catheter gastrostomy dislodgment. Reviewing all
      reported cases of gastrostomy related pancreatitis revealed higher incidence in
      patient with Foley catheter used as gastrostomy and revealed questionable trends
      in conducting tube replacement. We suggest a proper manner for tube replacement
      and concluded that should a Foley catheter used as a temporary solution a
      replacement should be schedule in a timely manner to avoid life threatening
      complications. 

PMID- 24674107
TI  - Preparation and characterization of nano liposomes of Orthosiphon stamineus
      ethanolic extract in soybean phospholipids.
AB  - BACKGROUND: O. stamineus is a medicinal herb with remarkable pharmacological
      properties. However, poor solubility of the active principles limits its
      medicinal value. This study sought to prepare nano liposomes of OS ethanolic
      extract in unpurified soybean phospholipids in order to improve its solubility
      and permeability. OS liposomes were prepared by the conventional film method, and
      were characterized for solubility, entrapment efficiency, Fourier transform
      infrared spectroscopy (FTIR), transmission electron microscopy (TEM), particle
      size and zeta potential, release, absorption in everted rat intestinal sacs, and
      DPPH scavenging effect. RESULTS: OS liposomes showed substantial enhancement of
      extract's solubility from 956 +/- 34 to 3979 +/- 139 MUg/ml, with entrapment
      efficiency of 66.2 +/- 0.9%. FTIR study indicates interaction between soybean
      phospholipids and OS extract. TEM and dynamic light scattering showed presence of
      round anionic nano liposomes with particle size and zeta potential of 152.5 +/-
      1.1 nm and -49.8 +/- 1.0 mV, respectively. A study using the fluorescent probe
      pyrene showed the critical micellar concentration is 9.2 +/- 2.9 MUg/ml. Release
      studies showed 94 +/- 0.1% release in non-formulated extract and 62.4 +/- 0.1% in
      OS liposomes. Released extract from OS liposomes showed improvement in DPPH
      scavenging effect, IC50 = 23.5 +/- 1.1 MUg/ml compared to 32.4 +/- 0.5 MUg/ml in
      non-formulated extract. OS liposomes were stable at pH 5.5 and 7.4, but showed
      reversible agglomeration at pH 1.6. Absorption in everted rat intestinal sacs
      showed substantial improvement in permeability of 3'-hydroxy-5, 6, 7, 4"
      tetramethoxyflavone, sinensetin, eupatorin, and 3 other unknown compounds.
      CONCLUSIONS: Enhanced solubility, absorption and antioxidant effect may improve
      the overall pharmacological effects and medicinal value of OS ethanolic extract.

PMID- 24674108
TI  - Intentional overdose of warfarin in an adult: anticoagulant reversal in the ED.

PMID- 24674109
TI  - Unusual cause of spontaneous unilateral intracerebral hematoma-acute methanol
      poisoning: case report.

PMID- 24674110
TI  - America's "best".

PMID- 24674111
TI  - Laborde tracheal dilator for exposure of the optic nerve.

PMID- 24674112
TI  - Editorial comment.

PMID- 24674113
TI  - Intermediate outcomes after female urethral reconstruction: graft vs flap.
AB  - OBJECTIVE: To evaluate the outcomes of women after urethral reconstruction with a
      vaginal flap urethroplasty (VFU) or dorsal buccal mucosal graft (BMG). METHODS:
      We retrospectively identified 10 women undergoing urethral reconstruction between
      February 2007 and October 2012. All patients had evidence of urethral stricture
      on cystoscopy and/or urodynamic study indicating bladder outlet obstruction.
      Recurrent stricture was defined using the same criteria. Follow-up included
      urethral calibration (>16F), symptom assessment, voiding cystourethrogram, and
      cystoscopy when there was difficulty voiding or symptoms recurred. RESULTS: Mean
      age was 49 years (range, 32-74). The indication for urethral reconstruction was
      urethral stricture in 9 patients. One woman had a traumatic 2-cm ventral urethral
      laceration associated with a pelvic fracture. Location was mid in 6 and distal in
      4 women. Average stricture length was 1.25 cm (range, 0.2-2). All patients with
      urethral stricture had previously undergone multiple urethral dilations. There
      were no major postoperative complications. Two patients undergoing VFU had a
      recurrent stricture requiring dilation. No patients undergoing dorsal BMG had a
      recurrent stricture. CONCLUSION: Female urethral reconstruction, either VFU or
      dorsal BMG, is a safe and successful procedure that should be offered to women
      with urethral strictures. The dorsal BMG approach is well tolerated and results
      are promising, but longer-term follow-up is needed. Women should be offered
      urethral reconstruction as a definitive management option rather than repeated
      urethral dilations.

PMID- 24674115
TI  - Clinical outcome of microsurgical varicocelectomy in infertile men with severe
      oligozoospermia.
AB  - OBJECTIVE: To evaluate the outcome of microsurgical varicocelectomy in infertile
      men with severe oligozoospermia and to identify the predictive parameters
      associated with the efficacy of microsurgical varicocelectomy in this cohort of
      patients. MATERIALS AND METHODS: This study included 102 consecutive severe
      oligozoospermic patients who underwent microsurgical varicocelectomy between 2000
      and 2013. The significance of several parameters as predictors of response to
      microsurgical varicocelectomy was evaluated using univariate and multivariate
      analyses. Responders were defined as those who fulfilled the following criteria:
      (1) sperm motility rate improved after surgery and (2) sperm concentration
      increased from <1 * 10(6)/mL to >= 5 * 10(6)/mL or from 1-5 * 10(6)/mL to >= 10 *
      10(6)/mL. RESULTS: After the mean postoperative observation period of 8.2 months,
      the mean sperm concentration increased from 2.4 to 11.6 million/mL (P <.001), and
      the mean sperm motility improved from 32.8% to 42.2% (P = .0024). There were no
      significant differences in the levels of hormonal parameters between the
      preoperative and postoperative measurements. Of the 102 patients, 42 (41.1%) were
      determined to be responders, and the wives of 17 (16.7%) conceived naturally.
      Univariate analysis identified preoperative sperm concentration (>= 2.0 vs <2.0
      million/mL) and laterality of varicocele (bilateral vs unilateral) as significant
      predictors of response to varicocelectomy. Only preoperative sperm concentration
      appeared to be independently related to the efficacy of varicocelectomy in men
      with severe oligozoospermia on multivariate analysis. CONCLUSION: Varicocelectomy
      may improve the sperm quality and fertility potential in men with severe
      oligozoospermia, particularly for those with relatively high sperm concentration.

PMID- 24674116
TI  - Urinary symptoms as a prodrome of bladder pain syndrome/interstitial cystitis.
AB  - OBJECTIVE: To test the hypothesis that more bladder pain syndrome/interstitial
      cystitis (BPS/IC) cases than controls report pre-onset urinary symptoms. METHODS:
      In a risk factor study, the date of BPS/IC onset (index date) was systematically
      determined in 312 female incident cases; the mean age at onset was 42.3 years.
      Frequency-matched controls were compared on pre-index date medical history.
      RESULTS: Three pre-index date symptoms were more common in BPS/IC cases: pelvic
      pain with urinary features, frequency, and bladder pain; 178 cases (57%) vs 56
      controls (18%) had at least 1 symptom (P <.001). Several perspectives suggested
      that prodromal symptoms were different from BPS/IC symptoms. In prodromal women,
      the median age of the earliest urinary symptom "more than other people" was 20
      years. Women with the prodrome were significantly more likely than those without
      to have pre-index date nonbladder syndromes (NBSs). The prodrome predicted not
      only BPS/IC but also a worse prognosis for it. CONCLUSION: Before the onset of
      BPS/IC, pelvic pain with urinary features, frequency, and/or bladder pain were
      reported by more than half the cases. Prodromal women recalled abnormal urinary
      symptoms decades before the onset of BPS/IC. The prodrome was associated with
      prior NBSs and predicted not only BPS/IC but also its poor prognosis. These data
      generated 2 hypotheses: that (1) prodromal symptoms are different from BPS/IC
      symptoms and (2) pain amplification links NBSs, the prodrome, the appearance of
      BPS/IC, and its poor prognosis. Recognition of the prodrome might provide
      opportunities for prevention of fully developed BPS/IC.

PMID- 24674117
TI  - Lean methodology improves efficiency in outpatient academic uro-oncology clinics.
AB  - OBJECTIVE: To determine if lean methodology, an industrial engineering tool
      developed to optimize manufacturing efficiency, can successfully be applied to
      improve efficiencies and quality of care in a hospital-based high-volume uro
      oncology clinic. METHODS: Before the lean initiative, baseline data were
      collected on patient volumes, wait times, cycle times (patient arrival to
      discharge), nursing assessment time, patient teaching, and physician ergonomics
      (via spaghetti diagram). Value stream analysis and a rapid improvement event were
      carried out, and significant changes were made to patient check-in, work areas,
      and nursing face time. Follow-up data were obtained at 30, 60, and 90 days. The
      Student t test was used for analysis to compare performance metrics with
      baseline. RESULTS: The median cycle time before the lean initiative was 46
      minutes. This remained stable at 46 minutes at 30 days but improved to 35 minutes
      at 60 days and 41 minutes at 90 days. Shorter wait times allowed for increased
      nursing and physician face time. The average length of the physician assessment
      increased from 7.5 minutes at baseline to 10.6 minutes at 90 days. The average
      proportion of value-added time compared with the entire clinic visit increased
      from 30.6% at baseline to 66.3% at 90 days. CONCLUSION: Using lean methodology,
      we were able to shorten the patient cycle time and the time to initial assessment
      as well as integrate both an initial registered nurse assessment and registered
      nurse teaching to each visit. Lean methodology can effectively be applied to
      improve efficiency and patient care in an academic outpatient uro-oncology clinic
      setting.

PMID- 24674118
TI  - Progression and remission of urologic symptoms in the community: results of a
      longitudinal cluster analysis approach.
AB  - OBJECTIVE: To investigate the natural history of urologic symptom progression and
      remission by means of cluster analysis in a large, well-characterized cohort of
      men and women. METHODS: Cluster analysis was used to assign men and women to
      symptom clusters on the basis of the prevalence of 14 self-reported urologic
      symptoms. Data were analyzed from the Boston Area Community Health study at
      baseline (T1) and 5-year follow-up (T2). Cluster progression was defined as any
      change from a less symptomatic to a more symptomatic cluster; conversely, cluster
      remission was defined as movement from more symptomatic to less symptomatic
      clusters. Logistic regression models examined the association of
      sociodemographic, psychosocial, and health outcome measures with cluster
      progression and remission. RESULTS: Follow-up data were available from 4145
      participants (1610 men; 2535 women). More than two thirds of men (69.2%) and
      women (68.2%) had stable symptom cluster assignments. Cluster progression
      occurred in 280 of 1610 (15.2%) men and 390 of 2535 (14.6%) women; cluster
      remission in 280 of 1610 (15.6%) men and 409 of 2535 (17.4%) women. In
      multivariate analyses, cluster progression was twice as common in men with
      incident depression (odds ratio = 2.43, 95% confidence interval 1.26-4.67) and 3
      times more likely in men with >= 3 comorbidities at baseline. Urologic surgeries
      were uncommon in men and women and were not consistently related to cluster
      progression or remission. CONCLUSION: Urologic symptom clusters were relatively
      stable over a 5-year follow-up period for more than two thirds of men and women
      in our sample. Specific risk factors for progression were identified in men and
      women.

PMID- 24674119
TI  - A 2-year review of recent Nuclear Regulatory Commission events: What errors occur
      in the modern brachytherapy era?
AB  - PURPOSE: To perform a retrospective analysis of recently reported brachytherapy
      errors to the Nuclear Regulatory Commission and to compare with historical
      trends. METHODS: All events reported in the 2-year period from January 1, 2009 to
      December 31, 2010 were categorized and analyzed. The 4 main areas of dose
      delivery were Gamma Knife radiosurgery, therapeutic radiopharmaceutical
      administration, high-dose-rate brachytherapy, and low-dose-rate brachytherapy.
      The different types of errors were wrong site, wrong dose, unintended exposure,
      lost or leaking source, or other. The causes of events were specified as the
      following: communication errors, equipment malfunction, human error, lack of
      training, or miscellaneous. RESULTS: One hundred and forty-seven events were
      found in the 2-year period. This error reporting rate far surpasses previous
      reports. The greatest number of events reported was for low-dose-rate
      brachytherapy, and the most common cause of error was human error. Wrong dose was
      the error that occurred most often, followed by wrong site. CONCLUSIONS: Very
      simple treatment errors, such as wrong patient, or wrong side of patient treated,
      are still occurring. Newer, complex deliveries such as high-dose-rate partial
      breast irradiation and low-dose-rate prostate brachytherapy also had a large
      number of events reported in this sampling. This report can help institutions
      establish needs for quality assessment and quality control processes.

PMID- 24674120
TI  - Low rate of clinician-scored gynecomastia induced by 6 months of combined
      androgen blockade in a randomized trial: Implications for prophylactic breast
      irradiation.
AB  - PURPOSE: To determine the incidence and predictors of clinician-scored
      gynecomastia induced by 6 months of combined androgen blockade (CAB) in a
      randomized trial. METHODS: We studied 94 men with intermediate or high-risk
      prostate cancer randomized to radiation plus 6 months of neoadjuvant CAB
      consisting of a gonadotropin-releasing hormone agonist and antiandrogen
      (flutamide). Patients were assessed for breast symptoms monthly as per protocol.
      Patients reporting breast tenderness or enlargement were then examined shirtless.
      RESULTS: Median age at entry was 72.1 years. While 52 patients (55.3%) reported
      either breast tenderness or enlargement, only 9 patients (9.6%) were scored as
      having gynecomastia when examined shirtless by a single clinician. Four patients
      received radiation for self-reported breast tenderness or enlargement without
      clinician-scored gynecomastia. If these 4 had not been radiated, the total
      incidence of clinician-scored gynecomastia may have been as high as 13 of 94
      (13.8%). No patient variable, such as age, body-mass index, and Adult Comorbidity
      Evaluation-27 score, or discontinuation of the antiandrogen, was associated with
      the development of gynecomastia. CONCLUSIONS: While many patients self-reported
      breast tenderness or enlargement with short-course CAB, the incidence of breast
      enlargement noticeable to an examiner when the patient was shirtless was less
      than 15%, which is much lower than the 60% to 80% rates typically reported with
      antiandrogen monotherapy. Given that the long-term risks of prophylactic breast
      irradiation are not well characterized, these data suggest that prophylactic
      breast irradiation may not be as necessary in men receiving short-course CAB.

PMID- 24674122
TI  - Determination of internal target volume using selective phases of a 4-dimensional
      computed tomography scan.
AB  - PURPOSE: Internal target volume (ITV) is frequently determined by contouring of
      gross tumor volumes (GTV) on 10 phases of a 4-dimensional computed tomography
      (4DCT) study set for lung cancer radiotherapy. This study aimed to investigate
      the possibility of generating ITV by using selective phases of a 4DCT scan.
      METHODS AND MATERIALS: The 4DCT scans of 20 patients with lung cancer were
      included in this study. GTVs were contoured on 10 phases in Focal4D (CMS, St
      Louis, MO). Different ITVs were derived by encompassing volumes of contours from
      selective phases. ITV10 was the combination of GTVs on all of the 10 phases and
      served as the gold standard volume. All of the other ITVs were smaller and within
      ITV10. The ratios of the volumes of these ITVs to ITV10 were calculated and used
      as a criterion to determine the similarity of different ITVs to ITV10. ITV2
      represented the ITV derived by using end-inhalation and end-exhalation (0% +
      50%). ITV3E was derived from contouring the 3 phases at end-inhalation, mid
      exhalation, and end-exhalation (0% + 20% + 50%). ITV3I was derived from
      contouring the 3 phases at end-inhalation, mid-inhalation, and end-exhalation (0%
      + 70% + 50%). ITV4 was derived by contouring the 4 phases at end-inhalation, mid
      inhalation, end-exhalation, and mid-exhalation (0% + 20% + 50% + 70%). ITV6E was
      derived from contouring the 6 consecutive phases during exhalation (0% + 10% +
      20% + 30% + 40% + 50%). ITV6I was derived from contouring the 6 consecutive
      phases during inhalation (50% + 60% + 70% + 80% + 90% + 0%). The volumes of ITVs
      were calculated and compared. RESULTS: ITV6I showed excellent agreement with
      ITV10 (volume ratio ITV6I/ITV10 = 0.975). ITV4 and ITV6E showed good agreement
      with ITV10 (ITV6E/ITV10 = 0.939, ITV4/ITV10 = 0.944). The volume ratios
      ITV3I/ITV10 and ITV3E/ITV10 were 0.927 and 0.906, respectively. ITV2 did not
      agree well with ITV10 (ITV2/ITV10 = 0.888). CONCLUSIONS: Contouring all phases
      during inhalation provides a good estimate of the ITV. However, the ITV may be
      underestimated if only contouring on 2 extreme phases.

PMID- 24674121
TI  - Assessing the risk of inadvertent radiation exposure of pregnant patients during
      radiation therapy planning and treatment in British Columbia.
AB  - PURPOSE: To explore health care professionals' perceptions of, and experience
      with, the risk of inadvertent radiation exposure to pregnant patients in
      radiation therapy (RT) departments. METHODS AND MATERIALS: The survey was
      distributed to 342 health care professionals working in RT departments in British
      Columbia (BC), including radiation therapists, medical physicists, radiation
      oncologists, and radiation oncology residents. RESULTS: There were 119 responses,
      65% of who were radiation therapists. Respondents' mean duration of experience
      was 13.9 years (range, 1-25), over which time the BC Cancer Agency has delivered
      at least one course of RT to an estimated 16,000 women under the age of 50. Of
      the responses, 11.6% indicated that they had ever, in their training or career,
      encountered a situation where RT was inadvertently given to a pregnant patient.
      Upon reviewing anonymous comments, at least 7 discrete incidents were described.
      Fifty-two percent of radiation oncologists never, or only occasionally,
      remembered to discuss the risk of RT in pregnancy; 53% did not believe there were
      signs posted in their cancer center warning patients or reminding staff of this
      risk. Furthermore, 61% did not know if there was any patient education material
      designed for this purpose. Establishment of a checklist to screen for potentially
      fertile females prior to RT was felt to be a useful intervention by 49% of
      respondents. CONCLUSIONS: There is a risk of RT exposure to pregnant patients.
      Procedures and policies to prevent inadvertent irradiation of pregnant patients
      appear to be inadequate in BC. Provincial policies should be introduced to help
      reduce the risk of inadvertent RT of pregnant patients.

PMID- 24674123
TI  - Three-dimensional visualization and dosimetry of stranded source migration
      following prostate seed implant.
AB  - PURPOSE: Computed tomographic (CT) imaging was used to determine the displacement
      of stranded seeds between day 0 and day 30 following prostate seed implants. Post
      plan dosimetry was used to assess the dosimetric consequence of strand
      displacement. METHODS AND MATERIALS: Between March 2006 and December 2009, 86
      prostate seed implant patients had day 0 and day 30 post-plan CT imaging.
      Migrated strands were first identified by inspection of day 0 and day 30 scans.
      The exact distance of displacement was measured using 3-dimensional fusion
      software. Post-plan dosimetric analysis was performed using CMS software.
      RESULTS: Of the 1550 strands placed, 23 strands exhibited substantial movement
      and these displacements occurred in 21 of the 86 cases. The measured distance of
      strand movement ranged from 0.31 cm to 3.44 cm, with mean displacement of 2.75
      cm. Of the displaced strands, 15 strands moved away from the implant center while
      8 strands moved toward the implant center. A comparison of changes in dosimetric
      parameters between day 0 and day 30 revealed expected increases in D90 related to
      resolution of prostate edema. When cases of strand displacement were compared
      with cases without displacement, there were no differences in D90 or V100 at day
      0. At day 30, however, statistically significant decreases in D90 (96.8% vs
      89.5%; P = .0061) and V100 (85.9% vs 82.2%; P = .046) were noted for cases with
      strand displacement. When the data were analyzed by looking at the change in
      dosimetric parameters over time for each individual case (eg, comparing the
      difference in D90 from day 0 to day 30 per patient) there was a trend toward
      decrease in D90 with displacement of the strands but this did not achieve
      statistical significance (P = .09). CONCLUSIONS: Stranded seeds show unexpected
      spatial instability in the craniocaudal dimension. Strand displacement may occur
      in approximately 1.5% of stranded sources placed and about 25% of cases. One may
      expect mean decreases in D90 and V100 of about 7% and 3%, respectively, among
      cases exhibiting strand migration in the first month following seed implant.
      Resolution of prostate edema during the same time period accounts for an
      approximately 30% increase in D90 and V100.

PMID- 24674124
TI  - Current clinical coverage of Radiation Therapy Oncology Group-defined target
      volumes for postmastectomy radiation therapy.
AB  - PURPOSE: The Radiation Therapy Oncology Group (RTOG) has published consensus
      guidelines for contouring relevant anatomy for postmastectomy radiation therapy
      (RT). How these contours relate to current treatment practices is unknown. We
      analyzed the dose-volume histograms (DVHs) for these contours using current
      clinical practice at University of Texas MD Anderson Cancer Center and compared
      them with the proposed treatment plans to treat RTOG-defined targets to full
      dose. METHODS AND MATERIALS: We retrospectively analyzed treatment plans for 20
      consecutive women treated with postmastectomy RT for which the treatment targets
      were the chest wall (CW), level III axilla (Ax3), supraclavicular (SCV), and
      internal mammary (IM) nodes. The RTOG consensus definitions were used to contour
      the following anatomic structures: CW; level I, II, and III axillary nodes (Ax1,
      Ax2, Ax3); SCV; IM; and heart (H). DVHs for these contours and the ipsilateral
      lung were generated from clinically designed treatment that had actually been
      delivered to each patient. For comparison regarding dose to normal tissue, new
      treatment plans were generated with the goal of covering 95% of the anatomic
      contours to 45 Gy. RESULTS: The prescribed dose was 50 Gy in each case. The mean
      percent of volumes that received 45 Gy (V45) for the RTOG guideline-based
      contours were CW 74%, Ax1 84%, Ax2 88%, Ax3 96%, SCV 84%, and IM 80%. Mean heart
      V10 values were 11% for treatment of left-sided tumors and 6% for right-sided
      tumors. Mean ipsilateral lung V20 values were 28% for left-sided tumors and 34%
      for right-sided tumors. For the contour-based plans, mean V45 values were CW 94%,
      Ax1 95%, Ax2 97%, Ax3 98%, SCV 98%, and IM 85%. Mean heart V10 values were 14%
      for treatment of left-sided tumors and 12% for right-sided tumors. Mean
      ipsilateral lung V20 values were 32% for left-sided tumors and 45% for right
      sided tumors. CONCLUSIONS: Clinically derived treatment plans, which have proven
      efficacy and are the current standard, cover 74% to 96% of the anatomy-based RTOG
      consensus volumes to the prescription dose. This discrepancy should be considered
      if treatment planning protocol guidelines are designed to incorporate these new
      definitions.

PMID- 24674125
TI  - Baroreflex failure following radiotherapy for head and neck cancer: A case study.

PMID- 24674126
TI  - Intact performance of a cochlear implant following radiotherapy in a child with
      acute lymphoblastic leukemia.

PMID- 24674127
TI  - Correlation of long-term pulmonary injury with radiation dose distribution in
      childhood cancer survivors.

PMID- 24674128
TI  - The impact of class III (morbid) obesity on heterotopic ossification outcomes.
AB  - PURPOSE: Obesity is associated with a chronic low inflammatory process that may
      act as common soil for the pathogenesis of obesity-related comorbidities
      including heterotopic ossification (HO). The purpose of this study is to compare
      the incidence of HO between patients with body mass index (BMI) <40 versus >=40
      after operative treatment of displaced acetabular fractures followed by radiation
      therapy (RT) +/- indomethacin. METHODS AND MATERIALS: This is a single
      institution retrospective chart review of 419 patients. All patients with well
      documented BMI underwent operative treatment followed by RT +/- indomethacin. All
      patients received 700 cGy to the soft tissues around the proximal femur and
      acetabulum without bone shielding. All RT were given postoperatively within 72
      hours. The patients were divided into 2 groups: Group (A) BMI < 40 and Group (B)
      BMI >=40. HO was assessed with X-ray. BMI was used as a surrogate measure to test
      the risk of HO despite prophylaxis. RESULTS: The incidence of HO among all
      patients is 21% (89 of 419), while among those in group A (BMI <40), 68 of 374
      patients developed HO (18%); in the morbidly obese group (BMI >=40) 21of 45
      patients developed HO (47%). The difference between the rates of HO in the 2
      groups was 29%; the chi(2) test showed a significant difference between the 2 BMI
      groups (P < .001 at alpha = 0.05). CONCLUSIONS: There is a higher incidence of HO
      among the morbidly obese patients despite RT +/- indomethacin. RT doses for HO
      prophylaxis in morbidly obese patients need to be reassessed; also, understanding
      the signaling pathways in target tissues in obese patients at which adipokines
      control metabolism may reveal novel therapies. Higher radiation doses +/-
      indomethacin may need to be considered and optimally evaluated in the context of
      a prospective, randomized clinical trial.

PMID- 24674129
TI  - Evaluation of dose variation to normal and critical structures for lung
      hypofractionated stereotactic body radiation therapy.
AB  - PURPOSE: To quantify the dose received by normal and critical structures during
      lung stereotactic body radiation therapy (SBRT) when registered to tumor or bone.
      METHODS AND MATERIALS: Sixteen patients with lung cancer receiving a total dose
      of 50 Gy in 4fractions for lung SBRT were retrospectively studied. Cone-beam
      computed tomography (CT) was performed for all fractions, and the images obtained
      were registered with planning CT with respect tosoft tissue for target
      localization. Isocenter shifts were determined for each fraction from differences
      between the bony and tumor alignments; doses were then recalculated based on the
      new isocenters and summed over all 4 fractions to compare against the planned
      normal and critical tissue dose. The normal and critical structures evaluated
      were total and ipsilateral lung, spinal cord, and esophagus. The first data
      collected were isocenter coordinate shifts in all 3 Cartesian coordinates for
      both tumor andbony alignments. The second were the dose differences to the normal
      and critical structures fromthe planned and recalculated doses for alignment
      based on the tumor. RESULTS: The study showed that while the maximum isocenter
      coordinate shifts in any direction couldbe as much as 1.60 cm, the normal and
      critical structure dose variations between the original plans and the simulated
      plans showed almost no change. The mean volume of total lung that receivedat
      least 20Gy difference for total lung and ipsilateral lung were 0.01% and -0.04%,
      respectively. For the esophagus, spinal cord, and heart the maximum and mean dose
      differences were 0.25 Gy and -0.04 Gy, -0.08 Gy and -0.02 Gy, and 0.02 Gy and
      0.05 Gy, respectively. CONCLUSIONS: Target localization using daily cone-beam CT
      with soft tissue registration was appropriate for minimizing the dose to the
      normal and critical structures without the need to re-plan due to the changes in
      the tumor position. For tumors located close to a critical structure, daily cone
      beam CT is recommended to determine the appropriate isocenter shifts.

PMID- 24674130
TI  - Screening colonoscopy before prostate cancer treatment can detect colorectal
      cancers in asymptomatic patients and reduce the rate of complications after
      brachytherapy.
AB  - PURPOSE: To investigate the incidence of undiagnosed, asymptomatic synchronous
      colorectal cancer (CRC) by using screening colonoscopy before brachytherapy, and
      to compare the subsequent rates of CRC and rectal toxicity in this screened
      population with those rates in unscreened patients after brachytherapy. METHODS
      AND MATERIALS: Patient, disease, and treatment characteristics, including history
      of colonoscopy and CR malignancy, were extracted from the medical records of all
      men who had undergone brachytherapy as monotherapy for low- or intermediate-risk
      prostate cancer at a single tertiary cancer care center between January 2000 and
      December 2009. The frequency of biopsy or polypectomy at screening colonoscopy,
      incidence of CR malignancy before and after prostate cancer diagnosis, and rate
      of brachytherapy toxicity including rectal bleeding were compared between men who
      had had screening colonoscopy before brachytherapy and men who had not. RESULTS:
      Of the 451 men identified, 268 had undergone screening colonoscopy during the 36
      months before brachytherapy and 183 had not. Of the 268 men who had had screening
      colonoscopy, 117 (44%) underwent biopsy or polypectomy, and 6 (3.2%) were found
      to have asymptomatic CRC. After brachytherapy, CRC was diagnosed in 3 (1.6%) of
      the 183 men who had not had screening colonoscopy before treatment versus 0 of
      the 268 men who had had screening colonoscopy (P = 0.035). Rectal toxicity was
      more common and more severe among men who had not undergone screening colonoscopy
      compared with those who had had screening colonoscopy before brachytherapy (14%
      vs 6%, P = 0.003). More unscreened patients (18% vs 5%) underwent
      postbrachytherapy colonoscopy (P < 0.001), with the potential of subjecting the
      irradiated rectum to biopsy. CONCLUSIONS: More than 3% of men with newly
      diagnosed prostate cancer in this study presented with undiagnosed, asymptomatic
      CRC, and the rate of postbrachytherapy rectal complications was higher among
      unscreened than among screened patients. We recommend screening colonoscopy for
      men who have not had CRC screening within the 3 years preceding prostate cancer
      diagnosis before radiation therapy to avoid unnecessary rectal biopsies and the
      associated risk of major complications.

PMID- 24674131
TI  - Measurement of vancomycin hydrochloride concentration in the exudate from wounds
      receiving negative pressure wound therapy: a pilot study.
AB  - It has been reported that negative pressure wound therapy (NPWT) is effective in
      the treatment of contaminated wounds. We hypothesised that systemically
      administered antibiotics migrate to wound site effectively by NPWT, which
      provides the antibacterial effect. We measured and compared the concentrations of
      vancomycin in the exudate and blood serum. Eight patients with skin ulcers or
      skin defect wounds who were treated with NPWT and were administered an
      intravenous drip of vancomycin were enrolled in this study. The wound surfaces
      were muscle, muscle fascia or adipose tissue. We administered vancomycin
      intravenously to NPWT patients (1-3 g/day). The exudate was obtained using 500 ml
      V.A.C. ATS canisters without gel. Three days later, the concentrations of
      vancomycin were measured. The mean concentration of vancomycin in the exudate
      from NPWT was 67% of the serum vancomycin concentration. We found that
      concentrations of vancomycin in NPWT exudates are higher than the previously
      reported concentrations in soft tissue without NPWT. The proactive use of NPWT
      might be considered in cases of suspected wound contamination when a systemic
      antibiotic is administered.

PMID- 24674133
TI  - Feasibility of pediatric plasma apheresis in intensive care settings.
AB  - Therapeutic plasma apheresis or exchange (TPE) in the pediatric population is
      technically challenging. Moreover, there is generally an apprehension in using
      TPE in children compared to adults. Recently, usage of TPE has evolved and is now
      being used in heterogenous clinical conditions. Its usefulness is classified by
      the American Society for Apheresis (ASFA) into various categories ranging from I
      to IV. The objective of this paper was to review the procedure in context of
      clinical indications, complications and outcomes in children. For this purpose,
      we retrospectively reviewed all TPE procedures performed on inpatients of 3 to 16
      years of age during a 6-year period (2007-2012). A total of 130 procedures were
      performed on 28 patients (M : F ratio of 1:1) with median age (range) of 8.8 (4
      16) years. All procedures were done using the continuous cell-separator
      centrifugal method. Due to organ dysfunctions, the majority of procedures (N = 26
      of 28 or 92% patients) were performed in the pediatric intensive care unit.
      Twenty-three, four and one patient belonged to ASFA categories I, II and III,
      respectively. The most common indications were neurological disorders (N = 13 or
      46.4%), comprised of Guillain-Barre syndrome (N = 10) and myasthenia gravis (N =
      3). Hematological disorders (N = 10 or 35.7%) including thrombotic
      thrombocytopenic purpura-hemolytic uremic syndrome were a close second. Complete
      recovery was seen in 23 patients (84%). Trivial adverse effects were observed in
      18/130 (13.8%) procedures. Major complications including cardiac arrest,
      hypotension and transfusion-related acute lung injury were observed in 5/130 or
      3.8% of procedures. However, there was no procedure-related death though five
      patients died during treatment due to underlying pathology. In conclusion, TPE is
      a safe and effective option in sick children for appropriate indications. An
      experienced staff with sound procedural skills is imperative for successful
      therapy.

PMID- 24674132
TI  - Biotrophy-specific downregulation of siderophore biosynthesis in Colletotrichum
      graminicola is required for modulation of immune responses of maize.
AB  - The hemibiotrophic maize pathogen Colletotrichum graminicola synthesizes one
      intracellular and three secreted siderophores. eGFP fusions with the key
      siderophore biosynthesis gene, SID1, encoding l-ornithine-N(5) -monooxygenase,
      suggested that siderophore biosynthesis is rigorously downregulated specifically
      during biotrophic development. In order to investigate the role of siderophores
      during vegetative development and pathogenesis, SID1, which is required for
      synthesis of all siderophores, and the non-ribosomal peptide synthetase gene
      NPS6, synthesizing secreted siderophores, were deleted. Mutant analyses revealed
      that siderophores are required for vegetative growth under iron-limiting
      conditions, conidiation, ROS tolerance, and cell wall integrity. Deltasid1 and
      Deltanps6 mutants were hampered in formation of melanized appressoria and
      impaired in virulence. In agreement with biotrophy-specific downregulation of
      siderophore biosynthesis, Deltasid1 and Deltanps6 strains were not affected in
      biotrophic development, but spread of necrotrophic hyphae was reduced. To address
      the question why siderophore biosynthesis is specifically downregulated in
      biotrophic hyphae, maize leaves were infiltrated with siderophores. Siderophore
      infiltration alone did not induce defence responses, but formation of biotrophic
      hyphae in siderophore-infiltrated leaves caused dramatically increased ROS
      formation and transcriptional activation of genes encoding defence-related
      peroxidases and PR proteins. These data suggest that fungal siderophores modulate
      the plant immune system. 

PMID- 24674134
TI  - The reinforcing effects of ethanol within the posterior ventral tegmental area
      depend on dopamine neurotransmission to forebrain cortico-limbic systems.
AB  - Ethanol can be self-infused directly into the posterior ventral tegmental area
      (pVTA) and these effects involve activation of local dopamine neurons. However,
      the neuro-circuitry beyond the pVTA involved in these reinforcing effects has not
      been explored. Intra-pVTA microinjection of ethanol increases dopamine release in
      the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and ventral pallidum
      (VP). The present study tested the hypothesis that the reinforcing effects of
      ethanol within the pVTA involve the activation of dopamine projections from the
      pVTA to the NAC, VP and mPFC. Following the acquisition of self-infusions of 200
      mg% ethanol into the pVTA, either the dopamine D2 receptor antagonist sulpiride
      (0, 10 or 100 MUM) or the D1 receptor antagonist SCH-23390 (0, 10 or 100 MUM) was
      microinjected into the ipsilateral NAC shell (NACsh), NAC core (NACcr), VP or
      mPFC immediately prior to the self-infusion sessions to assess the involvement of
      the different dopamine projections in the reinforcing effects of ethanol.
      Microinjection of each compound at higher concentration into the NACsh, VP or
      mPFC, but not the NACcr, significantly reduced the responses on the active lever
      (from 40-50 to approximately 20 responses). These results indicate that
      activation of dopamine receptors in the NACsh, VP or mPFC, but not the NACcr, is
      involved in mediating the reinforcing effects of ethanol in the pVTA, suggesting
      that the 'alcohol reward' neuro-circuitry consist of, at least in part,
      activation of the dopamine projections from the pVTA to the NACsh, VP and mPFC. 

PMID- 24674135
TI  - Neutrophil extracellular traps form predominantly during the organizing stage of
      human venous thromboembolism development.
AB  - BACKGROUND: A growing health problem, venous thromboembolism (VTE), including
      pulmonary embolism (PE) and deep vein thrombosis (DVT), requires refined
      diagnostic and therapeutic approaches. Neutrophils contribute to thrombus
      initiation and development in experimental DVT. Recent animal studies recognized
      neutrophil extracellular traps (NETs) as an important scaffold supporting
      thrombus stability. However, the hypothesis that human venous thrombi involve
      NETs has not undergone rigorous testing. OBJECTIVE: To explore the cellular
      composition and the presence of NETs within human venous thrombi at different
      stages of development. PATIENTS AND METHODS: We examined 16 thrombi obtained from
      11 patients during surgery or at autopsy using histomorphological,
      immunohistochemical and immunofluorescence analyses. RESULTS: We classified
      thrombus regions as unorganized, organizing and organized according to their
      morphological characteristics. We then evaluated them, focusing on neutrophil and
      platelet deposition as well as micro-vascularization of the thrombus body. We
      observed evidence of NET accumulation, including the presence of citrullinated
      histone H3 (H3Cit)-positive cells. NETs, defined as extracellular diffuse H3Cit
      areas associated with myeloperoxidase and DNA, localized predominantly during the
      phase of organization in human venous thrombi. CONCLUSIONS: NETs are present in
      organizing thrombi in patients with VTE. They are associated with thrombus
      maturation in humans. Dissolution of NETs might thus facilitate thrombolysis.
      This finding provides new insights into the clinical development and pathology of
      thrombosis and provides new perspectives for therapeutic advances.

PMID- 24674136
TI  - TSSAR: TSS annotation regime for dRNA-seq data.
AB  - BACKGROUND: Differential RNA sequencing (dRNA-seq) is a high-throughput screening
      technique designed to examine the architecture of bacterial operons in general
      and the precise position of transcription start sites (TSS) in particular.
      Hitherto, dRNA-seq data were analyzed by visualizing the sequencing reads mapped
      to the reference genome and manually annotating reliable positions. This is very
      labor intensive and, due to the subjectivity, biased. RESULTS: Here, we present
      TSSAR, a tool for automated de novo TSS annotation from dRNA-seq data that
      respects the statistics of dRNA-seq libraries. TSSAR uses the premise that the
      number of sequencing reads starting at a certain genomic position within a
      transcriptional active region follows a Poisson distribution with a parameter
      that depends on the local strength of expression. The differences of two dRNA-seq
      library counts thus follow a Skellam distribution. This provides a statistical
      basis to identify significantly enriched primary transcripts.We assessed the
      performance by analyzing a publicly available dRNA-seq data set using TSSAR and
      two simple approaches that utilize user-defined score cutoffs. We evaluated the
      power of reproducing the manual TSS annotation. Furthermore, the same data set
      was used to reproduce 74 experimentally validated TSS in H. pylori from reliable
      techniques such as RACE or primer extension. Both analyses showed that TSSAR
      outperforms the static cutoff-dependent approaches. CONCLUSIONS: Having an
      automated and efficient tool for analyzing dRNA-seq data facilitates the use of
      the dRNA-seq technique and promotes its application to more sophisticated
      analysis. For instance, monitoring the plasticity and dynamics of the
      transcriptomal architecture triggered by different stimuli and growth conditions
      becomes possible.The main asset of a novel tool for dRNA-seq analysis that
      reaches out to a broad user community is usability. As such, we provide TSSAR
      both as intuitive RESTful Web service ( http://rna.tbi.univie.ac.at/TSSAR)
      together with a set of post-processing and analysis tools, as well as a stand
      alone version for use in high-throughput dRNA-seq data analysis pipelines.

PMID- 24674137
TI  - Ethnicity and association with disease manifestations and mortality in Behcet's
      disease.
AB  - BACKGROUND: Behcet's disease (BD) significantly increases morbidity and
      mortality. BD mainly affects young adults with a peculiar geographical
      distribution. It has been suggested that BD varies in its phenotypic expression
      in different ethnic groups. METHODS: We investigated potential ethnicity-related
      differences relative to phenotype and prognosis of BD patients in a French
      multiethnic country. We included 769 consecutive patients fulfilling the
      international criteria of classification for BD, in the 3 largest ethnic groups
      of our cohort [European (n = 369), North African (n = 350) and sub Saharan
      African (n = 50)]. Factors that affect prognosis were assessed by multivariate
      analysis. RESULTS: 535 (69.6%) patients were male and the median (IQR) age at
      diagnosis was of 30.9 (24.9-37.2) years. Sub Saharan African BD patients had a
      higher frequency of CNS involvement (48% vs 32.3% vs 29.5%, p = 0 .035), a higher
      rate of death (12% vs 6% vs 3.5%, p = 0.029) and a lower frequency of HLA B51
      allele (29.4% vs 49.2% vs 55.8%, p = 0.009) compared to those from North Africa
      and Europe, respectively. Multivariate analysis showed that male gender (HR:
      5.01, CI: 1.51-16.65), cardiovascular involvement (HR: 2.24, CI: 1.15-4.36), and
      sub Saharan African origin (HR 2.62 (0.98-6.97) were independently associated
      with mortality. The 15-year mortality rate was of 19%, 9% and 6% in sub Saharan
      African, North African and European BD patients, respectively (p = 0.015).
      CONCLUSION: We reported ethnicity-related differences with respect to phenotype
      of BD. Sub Saharan Africans patients exhibited a worse prognosis.

PMID- 24674138
TI  - Divergent signaling pathways cooperatively regulate TGFbeta induction of cysteine
      rich protein 2 in vascular smooth muscle cells.
AB  - BACKGROUND: Vascular smooth muscle cells (VSMCs) of the arterial wall play a
      critical role in the development of occlusive vascular diseases. Cysteine-rich
      protein 2 (CRP2) is a VSMC-expressed LIM-only protein, which functionally limits
      VSMC migration and protects against pathological vascular remodeling. The
      multifunctional cytokine TGFbeta has been implicated to play a role in the
      pathogenesis of atherosclerosis through numerous downstream signaling pathways.
      We showed previously that TGFbeta upregulates CRP2 expression; however, the
      detailed signaling mechanisms remain unclear. RESULTS: TGFbeta treatment of VSMCs
      activated both Smad2/3 and ATF2 phosphorylation. Individually knocking down
      Smad2/3 or ATF2 pathways with siRNA impaired the TGFbeta induction of CRP2,
      indicating that both contribute to CRP2 expression. Inhibiting TbetaRI kinase
      activity by SB431542 or TbetaRI knockdown abolished Smad2/3 phosphorylation but
      did not alter ATF2 phosphorylation, indicating while Smad2/3 phosphorylation was
      TbetaRI-dependent ATF2 phosphorylation was independent of TbetaRI. Inhibiting Src
      kinase activity by SU6656 suppressed TGFbeta-induced RhoA and ATF2 activation but
      not Smad2 phosphorylation. Blocking ROCK activity, the major downstream target of
      RhoA, abolished ATF2 phosphorylation and CRP2 induction but not Smad2
      phosphorylation. Furthermore, JNK inhibition with SP600125 reduced TGFbeta
      induced ATF2 (but not Smad2) phosphorylation and CRP2 protein expression while
      ROCK inhibition blocked JNK activation. These results indicate that downstream of
      TbetaRII, Src family kinase-RhoA-ROCK-JNK signaling pathway mediates TbetaRI
      independent ATF2 activation. Promoter analysis revealed that the TGFbeta
      induction of CRP2 was mediated through the CRE and SBE promoter elements that
      were located in close proximity. CONCLUSIONS: Our results demonstrate that two
      signaling pathways downstream of TGFbeta converge on the CRE and SBE sites of the
      Csrp2 promoter to cooperatively control CRP2 induction in VSMCs, which represents
      a previously unrecognized mechanism of VSMC gene induction by TGFbeta.

PMID- 24674139
TI  - Clinical characteristics of foot ulceration in people with chronic gout.
AB  - Gout is the most common form of inflammatory arthritis and it has an affliction
      to the foot. Foot involvement in gout has been linked to foot pain, impairment
      and disability. There has been limited research on the effect of ulceration on
      foot pain, impairment, disability and health-related quality of life in patients
      already living with gout. The aim of the study was to describe the wound
      characteristics and the effect on foot pain, disability and health-related
      quality of life in patients with foot ulceration associated with gout.
      Participants were recruited from rheumatology clinics in Auckland, New Zealand.
      All the current foot ulceration sites and wound characteristics were recorded
      using the TIME wound assessment tool. The outcome measures included general pain,
      patient global assessment scale, foot pain, disability and impairment.
      Participants completed the Cardiff Wound Impact Schedule to assess the effect of
      ulcers on health-related quality of life. Sensory loss, vibrational thresholds
      and ankle brachial pressure index were collated to assess for lower limb arterial
      disease. Six participants were predominantly older men with a long duration of
      gout, high rates of obesity and co-morbidities such as hypertension,
      hyperlipidaemia, diabetes and cardiovascular disease. The mean (SD) duration of
      the foot ulcers was 4 (2) months. The majority of foot ulcers observed were 0.5
      cm(2) or smaller superficial thickness with surrounding callus. Partial thickness
      and full-thickness ulcers were also observed. Two patients presented with ulcers
      on multiple sites. There was only one case of infection. Gouty tophi were evident
      in most of the wounds. The dorsal aspect of the third toe was found to ulcerate
      in most cases. Moderate scores of foot pain, disability, impairment and health
      related quality of life were observed. Most participants wore shoes deemed as
      poor. Foot ulceration in gout is chronic and multiple ulcers can occur with the
      potential of leading to delayed wound healing, infection and a reduced quality of
      life. Poor footwear may contribute to the development and delayed healing of
      ulceration in people with gout. 

PMID- 24674141
TI  - Glomerular expression of myxovirus resistance protein 1 in human mesangial cells:
      possible activation of innate immunity in the pathogenesis of lupus nephritis.
AB  - Since viral infections activate type I interferon (IFN) pathways and cause
      subsequent release of IFN-dependent proinflammatory chemokines and cytokines, the
      innate immune system plays an important role in the pathogenesis of lupus
      nephritis (LN). It has been reported that human myxovirus resistance protein 1
      (Mx1), a type I IFN-dependent transcript, acts against a wide range of RNA
      viruses. Although the expression of Mx1 in biopsy specimens obtained from
      patients with dermatomyositis and cutaneous lupus has been described, the
      expression of Mx1 in human mesangial cells (MCs) has remained largely unknown. We
      treated normal human MCs in culture with polyinosinic-polycytidylic acid (poly
      IC), an authentic double-stranded RNA, and analyzed the expression of Mx1 by
      reverse transcription-polymerase chain reaction and western blotting. To
      elucidate the poly IC-signalling pathway, we subjected the cells to RNA
      interference against IFN-beta. We also conducted an immunofluorescence study to
      examine mesangial Mx1 expression in biopsy specimens from patients with LN. Poly
      IC-induced Mx1 expression in MCs are shown both time- and dose-dependently, and
      RNA interference against IFN-beta inhibited poly IC-induced Mx1 expression.
      Intense glomerular Mx1 expression was observed in biopsy specimens from patients
      with LN, whereas negative staining occurred in specimens from patients with IgA
      nephropathy or purpura nephritis. These preliminary observations support, at
      least in part, the theory of innate immune system activation in the pathogenesis
      of LN. 

PMID- 24674140
TI  - Physical activity and mental health in women with polycystic ovary syndrome.
AB  - BACKGROUND: Physical activity is prescribed as a component of primary management
      for Polycystic Ovary Syndrome (PCOS). This study investigates the association
      between physical activity and mental health as well as the exercise barriers,
      motivators and support providers for younger women with and without PCOS to
      assist in physical activity uptake and prescription for these women. METHODS:
      Women aged 18-50 years with (n = 153) and without PCOS (n = 64) completed a
      questionnaire at one time point. The questionnaire included the Hospital Anxiety
      and Depression Scale and a survey regarding levels of physical activity, physical
      activity barriers, motivators and supports. A MANCOVA assessed associations
      between physical activity, PCOS and mental health (specifically depression and
      anxiety). Descriptive and Chi square goodness of fit statistics assessed the
      differences in perceived barriers, motivators and support providers amongst women
      with and without PCOS. RESULTS: Women with PCOS displayed higher severity of
      depression (F(1,210) = 8.32, p = 0.004) and anxiety (F(1,210) = 17.37, p < 0.001)
      symptoms compared to controls. Overall, for physically active women, depression
      was significantly less severe than in their inactive counterparts (F(2,210) =
      13.62, p < 0.001). There were no differences in anxiety by physical activity
      status and no interaction effects between PCOS and activity status for depression
      or anxiety. Women with PCOS were more likely to report a lack of confidence about
      maintaining physical activity (Chi2 = 3.65; p = 0.046), fear of injury (Chi2 =
      4.08; p = 0.043) and physical limitations (Chi2 = 11.92; p = 0.001) as barriers
      to physical activity and were more likely to be motivated to be active to control
      a medical condition (Chi2 = 7.48; p = 0.006). Women with PCOS identified more
      sources of support compared to women without PCOS. CONCLUSIONS: Physical activity
      is associated with lower depression in women with PCOS and differences exist in
      the self-reported physical activity barriers, motivators and support providers,
      compared to controls. Being more active may offer mental health benefits in
      managing PCOS. Prescribing physical activity to women with PCOS should be
      individualized and consider both common and PCOS-specific barriers and motivators
      for successful engagement.

PMID- 24674142
TI  - Clinical features and mutation of NPHP5 in two Chinese siblings with Senior-Loken
      syndrome.
AB  - Senior-Loken syndrome is a rare syndromic form of nephronophthisis that is
      associated with retinal dystrophy. Presently, seven genes (NPHP1-6 and NPHP10)
      have been associated with Senior-Loken syndrome. NPHP5 mutations are known to
      cause classical Senior-Loken syndrome. Here, we report two sisters (II-4, II-5)
      from a Chinese Han ethnic family who presented with classical Senior-Loken
      syndrome. Both affected sisters exhibited Leber's congenital amaurosis and
      juvenile nephronophthisis that progressed to end-stage renal disease by the age
      of 16 years and 9 months in patient II-4 and 12 years and 9 months in patient II
      5. Sequence analysis showed a homozygous truncated mutation in NPHP5, c.1090C>T
      (p.R364X), in the patient II-4. This mutation is predicted to introduce a new
      open reading frame that results in the truncation of the C-terminal 235 amino
      acids of nephrocystin-5 and its consequent loss of function. Both parents carried
      a single heterozygous mutation in the same position, and no homozygous deletion
      of NPHP1 was found in this pedigree. 

PMID- 24674143
TI  - Red mercurochrome-associated acute kidney injury successfully treated by
      chelation therapy.

PMID- 24674144
TI  - Extreme metabolic alkalosis: excessive alkali intake due to ulcerative disease.

PMID- 24674145
TI  - Neuropathological staging of spinocerebellar ataxia type 2 by semiquantitative
      1C2-positive neuron typing. Nuclear translocation of cytoplasmic 1C2 underlies
      disease progression of spinocerebellar ataxia type 2.
AB  - Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder
      caused by the expansion of the trinucleotide CAG repeats encoding elongated
      polyglutamine tract in ataxin-2, the SCA2 gene product. Polyglutamine diseases
      comprise nine genetic entities, including seven different forms of
      spinocerebellar ataxias, Huntington's disease, and spinal and bulbar muscular
      atrophy. These are pathologically characterized by neuronal loss and intranuclear
      aggregates or inclusions of mutant proteins including expanded polyglutamine in
      selected neuronal groups. Previously, we examined immunolocalization of
      ubiquitin, expanded polyglutamine (probed by 1C2 antibody), and ataxin-2 in
      genetically confirmed SCA2 patients. In the present study, we expanded this
      approach by distinguishing different patterns of subcellular 1C2 immunoreactivity
      ("granular cytoplasmic," "cytoplasmic and nuclear" and "nuclear with
      inclusions.") and by quantifying their regional frequencies in three autopsied
      SCA2 brains at different stage of the disease. Comparison with neuronal loss and
      gliosis revealed that overall 1C2 immunoreactivity was paralleled with their
      severity. Furthermore, appearance of granular cytoplasmic pattern corresponded to
      early stage, cytoplasmic and nuclear pattern to active stage, and nuclear with
      inclusions pattern to final stage. We conclude that this 1C2-immunoreactive
      typing may be useful for evaluating the overall severity and extent of affected
      regions and estimating the neuropathological stage of SCA2. 

PMID- 24674146
TI  - Are we in a robotic surgical bubble market?

PMID- 24674147
TI  - The molecular biology of renal cancer: another piece of the puzzle.

PMID- 24674148
TI  - Caveat emptor.

PMID- 24674150
TI  - Predictors of adolescent smoking cessation and smoking reduction.
AB  - OBJECTIVE: To investigate the processes of change, demographic, health- and
      smoking-related predictors of both smoking cessation and smoking reduction in
      adolescents. METHODS: Data were drawn from a sample of 755 adolescent smokers who
      participated in a study testing the efficacy of a text messaging-based
      intervention for smoking cessation. Demographic, health- and smoking-related
      variables were assessed at baseline. Five processes of smoking cessation, derived
      from the Transtheoretical Model and the Social Cognitive Theory, as well as
      outcome measures were assessed at 6-month follow up. Univariate and multivariate
      regression analyses were conducted to identify baseline and process variables to
      predict smoking abstinence and smoking reduction. RESULTS: Male gender (OR=0.43,
      p<.01), lower alcohol consumption (OR=0.90, p=.05) and a lower number of
      cigarettes smoked per day at baseline (OR=0.87, p<.01) predicted smoking
      abstinence. Baseline physical activity predicted smoking reduction (OR=1.04,
      p=.03). None of the examined process variables significantly predicted smoking
      abstinence. The process variable "counter-conditioning" predicted smoking
      reduction (OR=1.46, p=.03). CONCLUSIONS: Baseline predictors of smoking cessation
      differ from predictors of smoking reduction. Dynamic or modifiable variables play
      an important role in predicting adolescent smoking cessation. PRACTICE
      IMPLICATIONS: Counter-conditioning might be an important element in adolescent
      smoking cessation interventions.

PMID- 24674151
TI  - Abstracts of the RCOG World Congress 2014, 28-30 March 2014, Hyderabad, India.

PMID- 24674149
TI  - Bacillus Calmette-Guerin strain differences have an impact on clinical outcome in
      bladder cancer immunotherapy.
AB  - BACKGROUND: Whether the commonly used bacillus Calmette-Guerin (BCG) strains
      Connaught and Tice confer different treatment responses in non-muscle-invasive
      bladder cancer (NMIBC) is unknown. OBJECTIVES: To compare clinical efficacy,
      immunogenicity, and genetics of BCG Connaught and Tice. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective randomized single-institution trial with treatment of
      142 high-risk NMIBC patients with BCG Connaught or Tice. INTERVENTION: Patients
      were randomized to receive six instillations of BCG Connaught or Tice. For
      experimental studies, BCG strains were compared in C57Bl/6 mice. Bladders and
      lymphoid tissues were analyzed by cytometry and the latter cultivated to detect
      live BCG. BCG genomic DNA was sequenced and compared with reference genomes.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence-free survival was the
      primary end point of the clinical study. The Kaplan-Meier estimator was used for
      estimating survival and time-to-event end points. Nonparametric tests served for
      the analysis of the in vivo results. RESULTS AND LIMITATIONS: Treatment with BCG
      Connaught conferred significantly greater 5-yr recurrence-free survival compared
      with treatment with BCG Tice (p=0.0108). Comparable numbers of patients
      experienced BCG therapy-related side effects in each treatment group (p=0.09). In
      mice, BCG Connaught induced stronger T-helper cell 1-biased responses, greater
      priming of BCG-specific CD8(+) T cells, and more robust T-cell recruitment to the
      bladder than BCG Tice. Genome sequencing of the BCG strains revealed candidate
      genes potentially involved in the differential clinical responses. CONCLUSIONS:
      BCG strain may have an impact on treatment outcome in NMIBC immunotherapy.
      PATIENT SUMMARY: We compared the efficacy of two commonly used bacillus Calmette
      Guerin (BCG) strains for the treatment of NMIBC and found that treatment with BCG
      Connaught prevented recurrences more efficiently than BCG Tice. Comparison of the
      immunogenicity of the two strains in mice indicated superior immunogenicity of
      BCG Connaught. We also identified genetic differences that may explain the
      differential efficacy of the Connaught and Tice BCG strains. TRIAL REGISTRATION:
      NCT00003779.

PMID- 24674153
TI  - Skeletal muscle loss is negatively associated with single-pool Kt/V and dialysis
      duration in hemodialysis patients.
AB  - We evaluated the skeletal muscle loss in hemodialysis (HD) patients by
      bioelectrical impedance analysis (BIA) and handgrip strength test. Thirty-four HD
      patients and 16 healthy subjects (control group) were measured for skeletal
      muscle mass normalized as the skeletal muscle mass index (SMI), calculated as
      skeletal muscle mass (kg)/height (m)(2) using a tetrapolar bioelectrical
      impedance plethysmograph. Handgrip strength test was also performed using a hand
      dynamometer in both groups. In HD patients, the associations of SMI and handgrip
      strength with age, sex, HD conditions, and HD parameters such as body mass index
      (BMI), single-pool Kt/V (spKt/V), normalized protein catabolic rate (nPCR),
      creatinine generation rate (CGR) and serum albumin level (Alb) were investigated.
      SMI of HD patients (4.58 +/- 0.95 kg/m(2) ) was significantly lower than that of
      the control group (5.55 +/- 0.80 kg/m(2) , P<0.01). The handgrip strength of HD
      patients (19.9 +/- 7.74 kg) was also significantly lower than that of the control
      group (33.0 +/- 8.94 kg, P<0.01). In HD patients, HD duration was associated with
      both SMI and handgrip strength. Among HD parameters, spKt/V was negatively
      associated with both SMI and handgrip strength, BMI and Alb were positively
      associated with SMI, while nPCR and CGR were associated with neither SMI nor
      handgrip strength. HD duration independently contributed to skeletal muscle loss
      and the value of spKt/V may be affected by skeletal muscle loss in HD patients.

PMID- 24674152
TI  - Fall risk-increasing drugs and falls: a cross-sectional study among elderly
      patients in primary care.
AB  - BACKGROUND: Falls are the most common cause of injuries and hospital admissions
      in the elderly. The Swedish National Board of Health and Welfare has created a
      list of drugs considered to increase the fall risk (FRIDs) and drugs that might
      cause/worsen orthostatism (ODs). This cross-sectional study was aimed to assess
      FRIDs and their correlation with falls in a sample of 369 community-dwelling and
      nursing home patients aged >=75 years and who were using a multi-dose drug
      dispensing system. METHODS: Data were collected from the patients' electronic
      medication lists. Retrospective data on reported falls during the previous three
      months and severe falls during the previous 12 months were collected. Primary
      outcome measures were incidence of falls as well as numbers of FRIDs and ODs in
      fallers and non-fallers. RESULTS: The studied sample had a high incidence of both
      reported falls (29%) and severe falls (17%). Patients were dispensed a mean of
      2.2 (SD 1.5) FRIDs and 2.0 (SD 1.6) ODs. Fallers used on average more FRIDs.
      Severe falls were more common in nursing homes patients. More women than men
      experienced severe falls. There were positive associations between number of
      FRIDs and the total number of drugs (p < 0.01), severe falls (p < 0.01) and
      female sex (p = 0.03). There were also associations between number of ODs and
      both total number of drugs (p < 0.01) and being community dwelling (p = 0.02). No
      association was found between number of ODs and severe falls. Antidepressants and
      anxiolytics were the most frequently dispensed FRIDs. CONCLUSIONS: Fallers had a
      higher number of FRIDs. Numbers of FRIDs and ODs were correlated with the total
      number of drugs dispensed. Interventions to reduce falls in the elderly by
      focusing on reducing the total number of drugs and withdrawal of psychotropic
      medications might improve the quality and safety of drug treatment in primary
      care.

PMID- 24674155
TI  - Patient willingness and barriers to receiving a CT scan for lung cancer
      screening.
AB  - CT scans are becoming a more common method for detecting lung cancers at an
      earlier, potentially more curable, stage of disease. There is currently little
      data on attitudes and beliefs about screening for lung cancer. This paper
      presents the results of a 2011 survey of adult current and former smokers that
      queried about past use of CT scanning and reasons for having or not having the
      screening done. A random-digit dialed telephone survey was administered to a
      representative sample of 1290 US adults. Logistic regression analyses were used
      to examine the correlates of having the test while controlling for the
      covariates. A total of 13.4% (n = 45) of the sample had ever had a CT scan to
      detect lung cancer. Of current smokers, 14.6% had received a CT scan, as compared
      with 12.7% of former smokers. The oldest age group (55+) was significantly more
      likely to have received a CT scan than the younger age groups. 78.5% of current
      smokers and 81.4% of former smokers indicated willingness to get the test if
      advised to do so by their doctor. Among those who said they were not willing to
      get screened, lack of insurance coverage was cited by 33% of current smokers and
      25% of former smokers. Additionally, 33% of current smokers were afraid to find
      out whether they had cancer. The main barrier to CT scanning for lung cancer is
      likely to be insurance coverage for the test, which would be a burden for those
      on limited and fixed incomes. Next steps should include further research into the
      effect of increased public education about the availability, risks, benefits and
      barriers to lung cancer screening.

PMID- 24674154
TI  - Influence of health locus of control on recovery of function in recently
      hospitalized frail older adults.
AB  - AIM: To investigate the influence of health locus of control on physical
      function, quality of life, depression and satisfaction with care transition in a
      sample of older adults after a hospital admission. METHODS: A total of 230 older
      adults referred for transition care after a hospital admission (mean length of
      stay 25.7 days, SD 17.2) were recruited into a randomized controlled intervention
      trial investigating the effect of specialized coaching compared with usual care.
      Older adults completed the multidimensional health locus of control (MHLC) survey
      at baseline. Self-rated quality of life, depression and physical function were
      assessed at baseline and 12 months using the EuroQol five-dimension, Geriatric
      Depression Scale (GDS) and Modified Barthel Index (MBI), respectively. RESULTS:
      Results from hierarchical multiple regression analysis in 136 participants (70
      usual care and 66 specialized care) with complete data showed that higher scores
      on the MHLC internal subscale were related to better quality of life, and better
      physical function in the usual care group at 12 months, but not depression or
      transition process satisfaction at 3 months. No relationships between MHLC
      subscales and outcome measures were observed in the specialized care group, where
      the coaching intervention might have precluded any relationship observed.
      CONCLUSIONS: A stronger sense of personal control over health was associated with
      better maintenance of quality of life and physical function at 12 months in older
      adults undergoing usual care transition after acute hospitalization. Modification
      of control beliefs has the potential to promote resilience and impact on health
      outcomes in older adults during care transitions.

PMID- 24674156
TI  - Evidence supporting contemporary post-operative radiation therapy (PORT) using
      linear accelerators in N2 lung cancer.
AB  - PURPOSE: Post-operative radiotherapy (PORT) treatment for lung cancer declined
      since a meta-analysis failed to show benefit in patients with N2 disease. Because
      several included studies employed outmoded radiation planning and delivery
      techniques, we sought to determine whether PORT with modern technology benefits
      patients with N2 disease. METHODS: We conducted searches of the published
      literature. For inclusion, studies must have included patients with stage III-N2
      lung cancer treated with PORT using only linear accelerators, used a control
      group that did not receive PORT, and reported outcome data for overall survival
      (OS). Prospective and retrospective analyses were included. Exclusion criteria
      were the use of cobalt devices or orthovoltage radiation. RESULTS: Data were
      evaluated with random-effects models. Three prospective and eight retrospective
      studies were included. The PORT and no-PORT groups included 1368 and 1360
      patients, respectively. The PORT group had significantly improved OS over the no
      PORT group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.62-0.96, P =
      0.020). Locoregional recurrence-free survival (LRFS) in 10 studies for which data
      was available was also improved in the PORT group (HR = 0.51, CI 0.41-0.65, P <
      0.001). CONCLUSIONS: PORT was associated with significantly lower risk of death
      and locoregional recurrence in patients with N2 lung cancer. Our study was
      limited by lack of access to individual patient data, which would have enabled
      more detailed analyses. Regardless, data thus far suggest PORT may be associated
      with a survival benefit. Given a lack of large-scale prospective data, clinical
      trials evaluating PORT with modern technology are warranted.

PMID- 24674157
TI  - Sensitive and specific detection of EML4-ALK rearrangements in non-small cell
      lung cancer (NSCLC) specimens by multiplex amplicon RNA massive parallel
      sequencing.
AB  - OBJECTIVES: Recurrent gene fusions of anaplastic lymphoma receptor tyrosine
      kinase (ALK) and echinoderm microtubule-associated protein-like 4 (EML4) have
      been recently identified in ~5% of non-small cell lung cancers (NSCLCs) and are
      targets for selective tyrosine kinase inhibitors. While fluorescent in situ
      hybridization (FISH) is the current gold standard for detection of EML4-ALK
      rearrangements, several limitations exist including high costs, time-consuming
      evaluation and somewhat equivocal interpretation of results. In contrast,
      targeted massive parallel sequencing has been introduced as a powerful method for
      simultaneous and sensitive detection of multiple somatic mutations even in
      limited biopsies, and is currently evolving as the method of choice for molecular
      diagnostic work-up of NSCLCs. MATERIALS AND METHODS: We developed a novel
      approach for indirect detection of EML4-ALK rearrangements based on 454 massive
      parallel sequencing after reverse transcription and subsequent multiplex
      amplification (multiplex ALK RNA-seq) which takes advantage of unbalanced
      expression of the 5' and 3' ALK mRNA regions. Two lung cancer cell lines and a
      selected series of 32 NSCLC samples including 11 cases with EML4-ALK
      rearrangement were analyzed with this novel approach in comparison to ALK FISH,
      ALK qRT-PCR and EML4-ALK RT-PCR. RESULTS: The H2228 cell line with known EML4-ALK
      rearrangement showed 171 and 729 reads for 5' and 3' ALK regions, respectively,
      demonstrating a clearly unbalanced expression pattern. In contrast, the H1299
      cell line with ALK wildtype status displayed no reads for both ALK regions.
      Considering a threshold of 100 reads for 3' ALK region as indirect indicator of
      EML4-ALK rearrangement, there was 100% concordance between the novel multiplex
      ALK RNA-seq approach and ALK FISH among all 32 NSCLC samples. CONCLUSION:
      Multiplex ALK RNA-seq is a sensitive and specific method for indirect detection
      of EML4-ALK rearrangements, and can be easily implemented in panel based
      molecular diagnostic work-up of NSCLCs by massive parallel sequencing.

PMID- 24674158
TI  - Editor's Note.

PMID- 24674159
TI  - The role of radiation oncologists and discussion of fertility preservation in
      young cancer patients.
AB  - PURPOSE: The risk of infertility increases after cancer treatment with
      chemotherapy, with radiotherapy, and in some cases with surgery. The goal of
      these secondary analyses was to examine potential differences in practice
      behaviors, specifically referral and discussion of fertility preservation, among
      oncologists (ie, surgical oncologists, medical oncologists, and radiation
      oncologists). METHODS AND MATERIALS: Two items examining discussion and referral
      for fertility preservation were administered as part of a larger 53-item survey
      measuring oncologists' fertility preservation knowledge, practice behaviors, and
      attitudes was developed and mailed to a nationally representative, stratified,
      random sample of US oncology care physicians. RESULTS: There was a significant
      difference by oncology subspecialty in discussion of the impact of treatment on
      future fertility for cancer patients of childbearing age. Follow-up chi(2) tests
      of discussion and specialty showed 82% of radiation oncologists "always/often"
      discussed the impact of treatment on fertility, compared with 51% for surgical
      oncologists. There was not a significant difference between oncology specialty
      and reported referrals to reproductive endocrinologist with 24% to 31% of all
      oncologist types reporting "rarely/never" referring patients of child-bearing age
      to an infertility specialist or reproductive endocrinologist. CONCLUSIONS: These
      findings are important particularly for radiation oncologists, who may have a
      unique role in communicating fertility preservation options to their patients
      given their opportunity for multiple patient encounters. As such, there is a
      notable opportunity for further research into the reasons why and how to
      implement provider education about fertility preservation to improve quality of
      life and quality care for patients of reproductive potential.

PMID- 24674160
TI  - Planning comparison of intensity modulated radiation therapy delivered with 2
      tangential fields versus 3-dimensional conformal radiotherapy for cardiac sparing
      in women with left-sided breast cancer.
AB  - PURPOSE: In women with unfavorable thoracic anatomy undergoing left breast
      radiation therapy (RT) after breast-conserving surgery, a significant volume of
      the heart may receive high-dose radiation, which has been shown previously to be
      associated with increased late cardiac morbidity and mortality. Use of intensity
      modulated radiation therapy (IMRT) has been proposed to reduce cardiac dose in
      these patients. We compared cardiac exposure from IMRT delivered from 2 opposed
      fields and 3-dimensional conformal radiation therapy (3DCRT) plans employing
      simple heart blocks. METHODS AND MATERIALS: Fourteen patients with left-sided
      breast cancer treated with breast-conserving surgery and RT were identified to
      have unfavorable cardiac anatomy, defined as maximum heart depth (MHD) >=1.0 cm
      within the unblocked opposed tangential fields. 3DCRT plans utilized dynamic
      wedges, segments, and custom heart blocks designed by the treating physician.
      Tangent IMRT plans were optimized to reduce cardiac dose while maintaining
      planning target volume (PTV) coverage equal to that achieved with the 3DCRT plan.
      We generated tangential field plans with complete heart block (CHB) or no heart
      block (NHB) for comparison. Plans were normalized to deliver 46 Gy to the PTV.
      Dose to the heart, PTV, and lumpectomy cavity were compared. RESULTS: Mean MHD
      was 1.44 cm (1.0-1.86 cm). There was no significant difference in PTV receiving
      >95% of the prescription dose between 3DCRT and IMRT, as intended. Mean V30 to
      the heart was 0% for CHB plans, 1.7% for 3DCRT plans, 1.8% for IMRT plans, and
      3.3% for NHB plans, respectively. There was no significant difference in heart
      V30 for 3DCRT and IMRT plans (P = .8). IMRT plans delivered 256 total monitor
      units compared with 201 in 3DCRT plans (P < .01). CONCLUSIONS: Inverse-planned
      tangent IMRT does not reduce high-dose radiation to the heart compared with
      3DCRT, incorporating a simple heart block in women with left-sided cancer and
      unfavorable cardiac anatomy when PTV coverage was equalized for both plans. In
      select patients with early-stage breast cancer and unfavorable thoracic anatomy,
      3DCRT with heart block may be sufficient to adequately protect the heart from
      high-dose radiation.

PMID- 24674161
TI  - Palliative radiotherapy in patients with esophageal carcinoma: A retrospective
      review.
AB  - PURPOSE: Palliative radiotherapy has traditionally been used as a noninvasive
      means of palliating dysphagia in patients with incurable esophageal cancer.
      Insertion of an esophageal stent is a traditional alternative and newer treatment
      modalities such as brachytherapy and laser therapy are being increasingly
      investigated and employed. There are few large series in the literature which
      examine the role of short palliative radiotherapy regimens in this patient group.
      This retrospective review aims to demonstrate the useful role that external beam
      radiotherapy can have in the palliation of patients with incurable esophageal
      carcinoma. METHODS AND MATERIALS: One hundred forty-eight patients with
      histologically proven esophageal cancer, who were unsuitable for radical
      treatment, were identified. Notes were reviewed to determine baseline
      characteristics, indications for radiotherapy, response to treatment, need for
      further intervention, time to further intervention, and survival. RESULTS: The
      median age of patients who received palliative radiotherapy was 74 years (range,
      31-91). Forty-nine percent of patients (n = 73) were performance status 2 or 3,
      70% (n = 103) had adenocarcinoma, 58% (n = 86) had locally advanced disease, and
      28% (n = 41) had metastatic disease. Ninety-three percent of patients (n = 138)
      complained of dysphagia prior to radiotherapy. Eighty-nine percent of patients (n
      = 132) received a dose of 20 Gy in 5 fractions. Only 2 patients (1%) failed to
      complete the prescribed course of treatment. Following radiotherapy, 75% of
      patients experienced an improvement in dysphagia and 25% of patients gained
      weight. Twenty-six percent of patients (n = 38) required subsequent insertion of
      an esophageal stent and a further 3% (n = 5) received retreatment with
      radiotherapy. The median stent (and retreatment)-free survival was 4.9 months.
      Median overall survival was 6.1 months. CONCLUSIONS: Despite a lack of randomized
      comparison to other modalities, external beam radiotherapy remains an effective,
      noninvasive, and generally well-tolerated means to palliate dysphagia in selected
      patients with incurable esophageal carcinoma.

PMID- 24674162
TI  - The remarkably distensible stomach: Case report highlighting the implications of
      gastric filling on radiation treatment planning for gastric lymphoma.

PMID- 24674163
TI  - Preservation of adrenal function after successful stereotactic body radiation
      therapy of metastatic renal cell carcinoma involving the remaining contralateral
      adrenal gland.

PMID- 24674164
TI  - Contouring inguinal and femoral nodes; how much margin is needed around the
      vessels?
AB  - PURPOSE: To determine the optimal margin needed around the femoral vessels for
      appropriate inguinofemoral lymph node coverage and to propose guidelines defined
      by anatomic boundaries for clinical target volume delineation. METHODS AND
      MATERIALS: Twenty-two patients with pelvic malignancies and involved inguinal
      lymph nodes treated with conformal radiation therapy were selected. Lymph nodes
      were considered positive if they were pathologically malignant by biopsy, had
      1(8)F-fluorodeoxyglucose avidity on positron emission tomography or measured
      >=1.5 cm on computed tomographic scan. We measured distance from the center of
      node(s) to the edge of the nearest femoral vessel. RESULTS: There were 52 total
      positive inguinal nodes among 22 patients. Relative to the femoral vessels, the
      location of the nodes were 51.9% anteromedial, 21.2% anterior, 11.5%
      anterolateral, 9.6% medial, 1.9% posterior, and 3.9% lateral. To cover >=90%
      disease, the margins needed around the nearest femoral vessel were anteromedial
      >=35 mm, anterior >=23 mm, anterolateral >=25 mm, medial >=22 mm, posterior >=9
      mm, and >=32 mm lateral. The corresponding anatomic boundaries were the
      following: laterally, medial border of the iliopsoas; medially, lateral border of
      adductor longus or medial end of pectineus; posteriorly, iliopsoas muscle
      laterally and anterior aspect of the pectineus muscle; medially and anteriorly,
      the anterior edge of the sartorius muscle. Most of the macroscopic nodes were
      medial or anteromedial to the femoral vessels. No patient had involved posterior
      or lateral nodes alone without positive nodes in the anterior or anteromedial
      positions. CONCLUSIONS: Circumferential margins around femoral vessels required
      to adequately cover this nodal region were >2 cm in most directions. Contouring
      the inguinal lymph nodes as a compartment defined by the anatomic landmarks
      suggested above may be more reproducible. Physicians should exercise caution in
      extrapolating pelvic nodal contouring guidelines to inguinal lymph nodal
      contouring.

PMID- 24674165
TI  - Regional treatment of vulvar cancer; lessons from the past and lessons for the
      future.

PMID- 24674166
TI  - De-intensification of treatment for human papilloma virus associated
      oropharyngeal squamous cell carcinoma: A discussion of current approaches.

PMID- 24674167
TI  - Stereotactic body radiation therapy and 3-dimensional conformal radiotherapy for
      stage I non-small cell lung cancer: A pooled analysis of biological equivalent
      dose and local control.
AB  - PURPOSE: To determine the relationship between tumor control probability (TCP)
      and biological effective dose (BED) for radiation therapy in medically inoperable
      stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-two
      studies on 3-dimensional conformal radiation therapy (3D-CRT) and SBRT for stage
      I NSCLC were reviewed for tumor control (TC), defined as crude local control >= 2
      years, as a function of BED. For each dose-fractionation schedule, BED was
      calculated at isocenter using the linear quadratic (LQ) and universal survival
      curve (USC) models. A scatter plot of TC versus BED was generated and fitted to
      the standard TCP equation for both models. RESULTS: A total of 2696 patients were
      included in this study (SBRT: 1640; 3D-CRT: 1056). Daily fraction size was 1.2-4
      Gy (total dose: 48-102.9) with 3D-CRT and 6-26 (total dose: 20-66) with SBRT.
      Median BED was 118.6 Gy (range, 68.5-320.3) and 95.6 Gy (range, 46.1-178.1) for
      the LQ and USC models, respectively. According to the LQ model, BED to achieve
      50% TC (TCD50) was 61 Gy (95% confidence interval, 50.2-71.1). TCP as a function
      of BED was sigmoidal, with TCP >= 90% achieved with BED >= 159 Gy and 124 Gy for
      the LQ and USC models, respectively. CONCLUSIONS: Dose-escalation beyond a BED
      159 by LQ model likely translates into clinically insignificant gain in TCP but
      may result in clinically significant toxicity. When delivered with SBRT, BED of
      159 Gy corresponds to a total dose of 53 Gy in 3 fractions at the isocenter.

PMID- 24674168
TI  - Variation in external beam treatment plan quality: An inter-institutional study
      of planners and planning systems.
AB  - PURPOSE: This study quantifies variation in radiation treatment plan quality for
      plans generated by a population of treatment planners given very specific plan
      objectives. METHODS AND MATERIALS: A "Plan Quality Metric" (PQM) with 14
      submetrics, each with a unique value function, was defined for a prostate
      treatment plan, serving as specific goals of a hypothetical "virtual physician."
      The exact PQM logic was distributed to a population of treatment planners (to
      remove ambiguity of plan goals or plan assessment methodology) as was a
      predefined computed tomographic image set and anatomic structure set (to remove
      anatomy delineation as a variable). Treatment planners used their clinical
      treatment planning system (TPS) to generate their best plan based on the
      specified goals and submitted their results for analysis. RESULTS: One hundred
      forty datasets were received and 125 plans accepted and analyzed. There was wide
      variability in treatment plan quality (defined as the ability of the planners and
      plans to meet the specified goals) quantified by the PQM. Despite the
      variability, the resulting PQM distributions showed no statistically significant
      difference between TPS employed, modality (intensity modulated radiation therapy
      versus arc), or education and certification status of the planner. The PQM
      results showed negligible correlation to number of beam angles, total monitor
      units, years of experience of the planner, or planner confidence. CONCLUSIONS:
      The ability of the treatment planners to meet the specified plan objectives (as
      quantified by the PQM) exhibited no statistical dependence on technologic
      parameters (TPS, modality, plan complexity), nor was the plan quality
      statistically different based on planner demographics (years of experience,
      confidence, certification, and education). Therefore, the wide variation in plan
      quality could be attributed to a general "planner skill" category that would lend
      itself to processes of continual improvement where best practices could be
      derived and disseminated to improve the mean quality and minimize the variation
      in any population of treatment planners.

PMID- 24674169
TI  - Plan quality and treatment planning technique for single isocenter cranial
      radiosurgery with volumetric modulated arc therapy.
AB  - PURPOSE: To demonstrate plan quality and provide a practical, systematic approach
      to the treatment planning technique for single isocenter cranial radiosurgery
      with volumetric modulated arc therapy (VMAT; RapidArc, Varian Medical systems,
      Palo Alto, CA). METHODS AND MATERIALS: Fifteen patients with 1 or more brain
      metastases underwent single isocenter VMAT radiosurgery. All plans were
      normalized to deliver 100% of the prescription dose to 99%-100% of the target
      volume. All targets per plan were treated to the same dose. Plans were created
      with dose control tuning structures surrounding targets to maximize conformity
      and dose gradient. Plan quality was evaluated by calculation of conformity index
      (CI = 100% isodose volume/target volume) and homogeneity index (HI = maximum
      dose/prescription dose) scores for each target and a Paddick gradient index (GI =
      50% isodose volume/100% isodose volume) score for each plan. RESULTS: The median
      number of targets per patient was 2 (range, 1-5). The median number of non
      coplanar arcs utilized per plan was 2 (range, 1- 4). Single target plans were
      created with 1 or 2 non-coplanar arcs while multitarget plans utilized 2 to 4 non
      coplanar arcs. Prescription doses ranged from 5-16 Gy in 1-5 fractions. The mean
      conformity index was 1.12 (+/- SD, 0.13) and the mean HI was 1.44 (+/- SD, 0.11)
      for all targets. The mean GI per plan was 3.34 (+/- SD, 0.42). CONCLUSIONS: We
      have outlined a practical approach to cranial radiosurgery treatment planning
      using the single isocenter VMAT platform. One or 2 arc single isocenter plans are
      often adequate for treatment of single targets, while 2-4 arcs may be more
      advantageous for multiple targets. Given the high plan quality and extreme
      clinical efficiency, this single isocenter VMAT approach will continue to become
      more prevalent for linac-based radiosurgical treatment of 1 or more intracranial
      targets and will likely replace multiple isocenter techniques.

PMID- 24674170
TI  - Spot scanning proton therapy for craniopharyngioma.

PMID- 24674171
TI  - Target volume changes through high-dose-rate brachytherapy for cervical cancer
      when evaluated on high resolution (3.0 Tesla) magnetic resonance imaging.
AB  - PURPOSE: To evaluate tumor volume changes that occurred during courses of high
      dose-rate brachytherapy (HDR) using high resolution (3.0 Tesla) magnetic
      resonance imaging (MRI), along with the regression after external beam radiation
      therapy (EBRT). METHODS AND MATERIALS: Fourteen patients with International
      Federation of Gynecology and Obstetrics stage IB1-IV cervical cancer were studied
      retrospectively. All patients underwent EBRT with concurrent chemotherapy
      followed by HDR brachytherapy. Gross tumor volume (GTV) and high-risk clinical
      target volume (HR-CTV) were contoured on a 3.0 Tesla MRI on the day of the HDR
      and on diagnostic MRI (1.5 Tesla) prior to EBRT. Two physicians independently
      contoured the GTV and HR-CTV on a total of 46 MRI data sets for the HDR plans.
      The percent volume changes of GTV and HR-CTV were quantified after EBRT and again
      after each HDR. The conformity indices (CIs) of the 2 contours were assessed.
      RESULTS: GTV and HR-CTV considerably regressed after the first ( --31.7% +/-
      19.3% and --26.4% +/- 6.9%, respectively) and the second (--26.8% +/- 14.3% and -
      23.8% +/- 11.0%) fraction of HDR while relatively small regressions were observed
      after the third (--16.3% +/- 14.2% and --10.6% +/- 13.4%) and the fourth (--8.0%
      +/- 3.4% and --9.0% +/- 8.0%) fractions. The lymph node-positive on positron
      emission tomography (PET) and stage III or IV group showed, on average, more than
      200% larger GTV and HR-CTV before EBRT than those of the other patients. The GTV
      and HR-CTV for the group were larger on average more than 150% after EBRT and
      before the first HDR fraction than the other group. Interobserver CI did not vary
      significantly (0.75 +/- 0.11) for HR-CTV, although a smaller CI (0.56 +/- 0.21)
      was found for GTV. CONCLUSIONS: Larger tumor regressions were observed after the
      first and second fractions of HDR than after all subsequent fractions. The PET
      identified lymph node-positive patient group and stage III or higher tumors
      showed larger tumor volumes before and after EBRT than other cases.

PMID- 24674172
TI  - Novel setup techniques for radiation treatment of severely obese patients with
      cervical cancer.

PMID- 24674173
TI  - Definitive radiation therapy for squamous cell carcinoma of the pharyngeal wall.
AB  - PURPOSE: To analyze the results of definitive radiation therapy (RT) for squamous
      cell carcinoma of the pharyngeal wall. METHODS AND MATERIALS: Between 1964 and
      2009, 170 patients were treated with definitive RT; all living patients had a 1.7
      year minimum follow-up. RESULTS: The 5-year rates of local control and ultimate
      local control were the following: T1, 93% and 93%; T2, 84% and 91%; T3, 60% and
      62%; and T4, 44% and 44%. Multivariate analysis revealed stage I-II tumors,
      female gender, and altered fractionation were associated with improved local
      regional control. The 5-year cause-specific and overall survival rates were the
      following: I, 88% and 50%; II, 89% and 57%; III, 49% and 31%; IV, 35% and 21%;
      and overall, 50% and 31%, respectively. Fatal complications occurred in 9
      patients (5%). CONCLUSIONS: Local-regional control and survival are related to
      extent of disease and treatment technique. Although outcomes have improved in
      recent years, the morbidity of treatment is significant and a substantial
      proportion of patients die due to cancer.

PMID- 24674174
TI  - Radiotherapy following gross total resection of adult soft tissue sarcoma of the
      head and neck.
AB  - PURPOSE: This study reports the outcomes of adults with soft tissue sarcoma (STS)
      of the head and neck following resection and postoperative radiotherapy (RT), and
      provides a framework for explaining the issues that radiation oncologists must
      understand to manage patients with this diverse group of tumors. METHODS AND
      MATERIALS: Twenty-four patients met the following inclusion criteria of this
      study: age >=19 years, head or neck primary site, STS, with the exception of
      rhabdomyosarcoma, Ewing, or angiosarcoma variants, and curative-attempt treatment
      with gross total tumor resection followed by RT. RESULTS: All patients underwent
      gross total tumor resection followed by adjuvant RT at our institution during the
      28-year period between June 1, 1981, and December 31, 2009. This is a mature
      study with a median follow-up of 11 years (range, 0.6-27 years). No patient was
      lost to follow-up. All recurrences were at the primary site. No patient developed
      an isolated regional or distant recurrence. No patient developed synchronous
      nodal or distant recurrences at the time of local recurrence. Half of the
      recurrences presented within 1 year of completing RT, but there were 2 cases
      where we did not detect recurrence until years 6 and 8 after RT. No recurrence
      was successfully salvaged. The actuarial rate of local control and relapse-free
      survival was 83% (95% CI [confidence interval], 63%-94%) at 5 years and 73% (95%
      CI, 51%-87%) at 10 years. The incidence of moderate to severe treatment
      complications was 4%. CONCLUSIONS: Our series documents that gross total
      resection followed by RT cures most patients (75%) with the most common types of
      STS of the head and neck. All recurrences were local, meaning near the primary
      site in tissue that received the full RT prescription dose. For this reason,
      modifying the approach to treatment of the primary tumor site is the only
      strategy that will meaningfully improve outcomes for this group of patients.

PMID- 24674175
TI  - Nelfinavir treatment of adenoid cystic carcinoma: A case report.

PMID- 24674176
TI  - Presumed early-stage lung cancer treated with stereotactic body radiation therapy
      in a medically inoperable patient with multiple connective tissue disorders.

PMID- 24674177
TI  - Radiotherapy for hilar or mediastinal lymph node metastases after definitive
      treatment with stereotactic body radiotherapy or surgery for stage I non-small
      cell lung cancer.
AB  - PURPOSE: Management of regional lymph node (LN) recurrence is an important issue
      in definitive treatment of non-small cell lung cancer (NSCLC). We evaluated
      clinical outcomes of conventional radiotherapy for hilar or mediastinal LN
      metastases developing after stereotactic body radiotherapy (SBRT) or surgery for
      stage I NSCLC. METHODS AND MATERIALS: Between 2004 and 2008, 26 patients with
      hilar or mediastinal LN metastases without local recurrence and distant
      metastasis after SBRT (n = 14) or surgery (n = 12) were treated with conventional
      radiotherapy. Twelve of the 14 post-SBRT patients (86%) were judged medically
      inoperable at the time of SBRT. All patients were treated to the hilum and
      mediastinum with conventional daily fractions of 2.0 Gy (n = 25) or 2.4 Gy (n =
      1). The median total dose for treating metastatic LN was 60 Gy (range, 54-66 Gy)
      for the post-SBRT patients and 65 Gy (range, 60-66 Gy) for the post-surgery
      patients. Only 1 of the 14 post-SBRT patients and 8 of the 12 post-surgery
      patients received chemotherapy. RESULTS: For all 26 patients, the overall and
      cause-specific survival rates at 3 years from radiation for LN metastases were
      36% and 51%, respectively (14% and 39%, respectively, for the 14 post-SBRT
      patients and both 64% for the 12 post-surgery patients). Three of the SBRT
      patients were alive at 35 to 43 months with (n = 2) or without (n = 1) further
      recurrence, and 4 of the post-surgery patients were alive at 36 to 62 months with
      (n = 2) or without (n = 2) further recurrence. The incidence of >=grade 2
      pulmonary toxicity was 49% at 1 year (53% for post-SBRT patients and 44% for post
      surgery patients). A grade 5 pulmonary toxicity was observed in 1 of the post
      SBRT patients. CONCLUSIONS: Conventional radiotherapy could successfully salvage
      LN relapses after SBRT as well as after surgery in 7 of 26 patients. Radiotherapy
      in this setting appears reasonably well tolerated.

PMID- 24674178
TI  - Intensity modulated radiation therapy class solutions in Philips Pinnacle
      treatment planning for central nervous system malignancies: Standardized,
      efficient, and effective.
AB  - BACKGROUND: The use of intensity modulated radiation therapy (IMRT) is becoming
      more commonplace in the treatment of central nervous system (CNS) malignancies.
      However, the determination of beam arrangements is still an empirical process,
      and optimization of any given plan may take hours on the part of the dosimetrist
      and the physician to achieve optimal conformity and normal tissue doses. Regional
      CNS class solutions (CS) for IMRT planning with the Philips Pinnacle treatment
      planning system (version 8.0; ADAC Laboratories, Milpitas, CA) have been in
      partial implementation at our institution since 2009. The purpose of this present
      work was to investigate their validity in clinical practice. MATERIALS AND
      METHODS: The plans of 55 patients treated for high-grade gliomas since 2009 were
      analyzed retrospectively. Thirty plans were categorized as having been planned
      with class solutions and 25 plans with user-defined optimization. Each plan was
      evaluated based on the following: (1) mean dose to the brain; (2) brain V30; and
      (3) Radiation Therapy Oncology Group (RTOG) conformity index (CIRTOG). These data
      were then compared with 140 historical benchmark plans that were generated using
      user-defined optimization prior to 2009. RESULTS: The CS plans for gliomas in
      frontal, parietal-occipital, and temporal regions typically resulted in superior
      mean brain dose, brain V30, and conformity index when compared with user-defined
      plans. The CS plans for brainstem gliomas exhibited improved CIRTOG, but not
      brain V30 and brain mean dose. In trials of planning efficiency, the CS technique
      reduced treatment planning time by more than 2 times, independent of prior
      planning experience. CONCLUSIONS: We have developed a CS protocol for IMRT
      planning of gliomas that has dramatically simplified this complex planning
      process, allowing dosimetrists of all levels of experience to produce highly
      conformal plans in a time efficient manner.

PMID- 24674179
TI  - Radiation oncology information systems and clinical practice compatibility:
      Workflow evaluation and comprehensive assessment.
AB  - PURPOSE: To map the level of clinical practice compatibility with a radiation
      oncology information system (ROIS) through a workflow- and clinical process-based
      method aimed at optimizing the safety, efficacy, and efficiency of patient care;
      to improve the understanding of the critical relationship between the clinical
      practice and ROIS. METHODS AND MATERIALS: Clinic-specific workflow and
      infrastructure were classified into clinical processes, information management,
      and technological innovation integration. Clinical information systems
      information technology infrastructure and process maps were generated by a team
      of experts, representing clinical constituents. These maps served as the basis
      for evaluating connectivity and process flow and to guide the development of a
      quantitative survey where all clinical tasks and subprocesses were ranked
      according to importance in patient care and scored by the team of experts for
      performance. Process maps and survey output were used to measure ROIS
      compatibility with the practice and to guide practice improvement. RESULTS:
      Practice-specific process and infrastructure maps were generated. The developed
      survey was applied and results indicate a range of ROIS compatibility with
      clinical workflow and infrastructure. Survey results combined with experiential
      feedback provided specific prioritized guidance to improve both ROIS performance
      and clinic-specific processes and infrastructure. CONCLUSIONS: This work provides
      a systematic and customizable tool to understand and evaluate clinical
      information and workflow and its compatibility with a given ROIS. The analysis
      provides insight into workflow improvements and information systems and
      information technology infrastructure limitations. Participating in such a
      process provides the entire team with a deeper understanding of the critical
      relationship between the clinical practice and the ROIS.

PMID- 24674180
TI  - Feasibility and advantages of using flattening filter-free mode for radiosurgery
      of multiple brain lesions.
AB  - PURPOSE: The 6-MV flattening filter-free mode (6F) of the Varian TrueBeam (Varian
      Medical Systems, Palo Alto, CA) enables faster dose delivery and shortens
      treatment time, which are especially beneficial for stereotactic radiosurgery.
      This study is to evaluate the feasibility and advantages of using 6F in
      stereotactic radiosurgery treatment of multiple brain lesions in comparison with
      regular 6-MV mode (6X). MATERIALS AND METHODS: Ten patients having 2-12 brain
      metastases treated by intensity modulated stereotactic radiosurgery were selected
      for this study. For each patient, 2 RapidArc (RA; Varian Medical Systems) plans
      were generated: one using the 6F mode with a dose rate of 1400 monitor units
      (MU)/minute and another using the regular 6X mode of 600 MU/minute for a Varian
      TrueBeam linac. For each patient, both plans employed the same beam arrangement
      and optimization process. RESULTS: The dosimetric parameters of homogeneity,
      conformity, and gradient indices were calculated and found to be comparable in
      the 6F and 6X plans for each patient. The mean dose to the normal brain and
      maximal doses to brainstem, chiasm, eyes, and optical nerves were also comparable
      in both RA plans using either 6F or 6X. The total number of MUs in the RA plans
      using 6F was 10%-20% more than that in the RA plan using 6X, but the beam-on-time
      was much less if 6F was used for planning and dose delivery (50% less).
      CONCLUSIONS: The fast delivery of the 6F beam is not only beneficial in
      stereotactic radiosurgery of a single brain lesion, but also for treating
      multiple brain lesions (2-12 lesions in this study group). Due to the beam
      falloff away from the central axis for large field sizes, more MUs are needed for
      6F beams as compared with 6X. However, for the 6F mode with 1400 MU/minute, the
      delivery times are still much shorter compared with the 6X mode, thus greatly
      shortening the treatment time.

PMID- 24674181
TI  - Can trained volunteers provide psychosocial support to patients undergoing
      radiotherapy? The perspective of patients and volunteers.
AB  - PURPOSE: Clinic-based psychosocial interventions, including volunteer-based ones,
      may be a cost-efficient and acceptable means of integrating psychosocial support
      into cancer care during radiotherapy. The present study evaluated a new
      psychosocial volunteer support program in a large radiotherapy clinic. METHODS
      AND MATERIALS: Patients were asked to complete a demographic and satisfaction
      with care questionnaire. Clinic volunteers were asked to report their
      interactions with patients on shift logs. RESULTS: Of the 182 participating
      patients, 93 (51%) recalled meeting a volunteer in the clinic, with the 2 most
      common support types provided being the following: "listening and caring," and
      "information on services." Analysis of 224 volunteers' shift logs indicated that
      almost all interactions (94%) were initiated by the volunteers, and almost half
      (47%) involved the patients' companions in the clinic. The most common support
      type documented was "information and navigation" (71%), followed by "emotional"
      (47%), "diversional" (21%), and "physical/practical" (17%) support. CONCLUSIONS:
      Trained volunteers can effectively provide clinic-based psychosocial support and
      information to a high proportion of radiotherapy patients. These findings
      demonstrate that volunteer support is a feasible means of meeting the
      psychosocial needs of patients with cancer attending outpatient radiotherapy
      clinics, who may not require or want professional psychosocial support.

PMID- 24674182
TI  - Physician assistant and nurse practitioner utilization in radiation oncology
      within an academic medical center.
AB  - PURPOSE: To assess the utilization of physician extenders working in radiation
      oncology in an academic medical center and to identify opportunities to improve
      their utilization. METHODS AND MATERIALS: A workload analysis and patient flow
      analysis were conducted on physician extenders employed by the University of
      Michigan Health System Radiation Oncology Department in order to better
      understand their utilization and impact on patient flow. RESULTS: Nearly half
      (46%) of physician extender time was spent performing indirect patient care.
      Physician extenders performed most (84.3%) of the first encounters for follow-up
      appointments; however, these patients were seen independently by physician
      assistants (PAs) and nurse practitioners (NPs) only 51% of the time. Physician
      extenders perceived their utilization within the department would be improved
      with well-defined position goals (80%), less clerical work (40%), more
      involvement in treatment planning (40%), more training (40%), and more
      involvement with new patient consults (20%). Physicians felt the utilization of
      physician extenders could be improved by providing more training (33%), increased
      physician extender involvement in treatment planning (22%), increased physician
      extender involvement in new patient consults (11%), and increased autonomy (11%).
      CONCLUSIONS: This study highlights the importance of collecting data to allow for
      evaluation of PA and NP performance and utilization. We have highlighted a unique
      methodology for analyzing physician extender duties and workflow that could be
      employed by other organizations and medical practices, regardless of specialty,
      to examine PA and NP deployment and to identify opportunities to optimize their
      utilization.

PMID- 24674183
TI  - Audit tool for external beam radiation therapy departments.
AB  - PURPOSE: Development of a self-contained audit tool for external beam radiation
      therapy to assess compliance with the major recommendations from professional
      organizations and generally accepted standards of practice. Intensity modulated
      radiation therapy, stereotactic body radiation therapy, stereotactic
      radiosurgery, and volumetric modulated arc therapy were included in this review.
      METHODS AND MATERIALS: A physics quality working group developed a department
      vision, distinguished and summarized key references, and condensed important
      elements of good documentation practices. The results were then compiled in a
      checklist format and used to perform audits at 3 sites. RESULTS: The final audit
      tool contains 65 items spanning a wide range of external beam radiation therapy
      practices. Several of the audit items address issues not commonly identified by
      other authoritative sources. A total of 48 process improvements were identified
      at the 3 sites audited. CONCLUSIONS: The enclosed self-inspection list may be
      useful to a site as an annual review tool, as an aid in preparation for the
      American College of Radiology-American Society for Therapeutic Radiology and
      Oncology practice accreditation, or as a catalyst for general quality
      improvement. Sites can quickly identify opportunities for improvement by
      concentrating on high importance items and commonly identified areas of
      noncompliance.

PMID- 24674184
TI  - Use of intensity modulated radiation therapy to reduce acute and chronic
      toxicities of breast cancer patients treated with traditional and accelerated
      whole breast irradiation.
AB  - PURPOSE: The purpose of this analysis was to examine the impact of applying
      intensity modulated radiation therapy (IMRT) on toxicity with traditional and
      accelerated whole breast irradiation (AWBI). METHODS AND MATERIALS: A total of
      335 patients with stage 0-IIB breast cancer were treated with either a
      conventional wedge technique (S-WBI, n = 87), IMRT (I-WBI, n = 93), or AWBI with
      IMRT (I-AWBI, n = 155). S-WBI and I-WBI patients received a median dose of 45 Gy
      to the breast with a median 16-Gy tumor bed boost for a cumulative median dose of
      61 Gy. I-AWBI patients received a median dose of 42.56 Gy via an accelerated IMRT
      plan, without a boost. Acute and chronic toxicities were assessed using Common
      Toxicity Criteria v.3.0. RESULTS: Median follow-up was 11.0, 9.1, and 1.1 years
      for S-WBI, I-WBI, and I-AWBI patients, respectively. When comparing patients of
      all breast sizes, I-WBI showed decreased incidences of grade 2+ acute radiation
      dermatitis and induration compared with I-AWBI (1% vs 23%, P < .001/0% vs 5%; P =
      .05 ) and S-WBI (1% vs 12%, P = .007/0% vs 6%; P = .02). I-WBI also had lower
      rates of chronic edema compared with S-WBI patients (3% vs 13%, P = .03). In
      larger breasted patients, I-WBI was associated with reduced acute toxicities
      compared with S-WBI with regard to grade 2 + dermatitis and edema (0% vs 19%, P =
      .02/7% vs 24%, P = .06). No differences were seen between I-WBI and I-AWBI with
      IMRT techniques with the exception of increased acute radiation dermatitis in I
      AWBI patients (0% vs 38%, P < .001). CONCLUSIONS: This analysis confirms previous
      data which have demonstrated that RT with IMRT is associated with reduced
      toxicities compared with conventional techniques. In larger breasted women, with
      the exception of acute skin reactions, I-AWBI showed comparable rates of
      toxicities compared with I-WBI. These data support the use of IMRT to expand the
      role of AWBI and the currently accruing Radiation Therapy Oncology Group 1005
      trial.

PMID- 24674185
TI  - Definitive treatment of supernumerary lower chest wall primary breast cancer.

PMID- 24674186
TI  - Angiosarcoma of the breast following breast conservation therapy: A case report
      and review of the literature.

PMID- 24674187
TI  - Radiation recall reaction with anastrozole treatment in breast cancer.

PMID- 24674188
TI  - Salvage craniospinal irradiation with an intensity modulated radiotherapy
      technique for patients with disseminated neuraxis disease.
AB  - PURPOSE: To report the use and results of a novel intensity modulated
      radiotherapy (IMRT)-based technique used for salvage craniospinal irradiation
      (CSI) in 6 patients who developed neuraxis disease after initial high-dose
      conformal radiotherapy (RT) to the brain. METHODS AND MATERIALS: After
      Institutional Review Board approval, all patients treated for disseminated
      leptomeningeal disease with salvage CSI using IMRT with conventional external
      beam radiotherapy were identified. The medical records and radiotherapy dosimetry
      were reviewed. Tolerance, morbidity, tumor control, and overall survival were
      evaluated. RESULTS: Six patients who received IMRT-based salvage CSI were
      identified. The median age was 6.5 years (range 2- 34 years) at initial RT and
      7.7 years (range, 3-35 years) at salvage CSI. Disease progression necessitating
      salvage CSI was noted at a median of 10 months (range, 1-26 months) from the
      initial RT. The original disease site remained well controlled in all 6 patients.
      The median dose of the initial RT treatment was 52 Gy (range, 30.6-60 Gy).
      Salvage CSI dose was 36 Gy in 20 fractions in all 6 patients. IMRT was used to
      treat the cranial contents excluding the previously treated area. Five pediatric
      patients received electron beams to spine and 1 adult patient received photon
      beams to spine. IMRT allowed a conformal and uniform dose distribution to the
      target tissue while excluding previously treated areas. Salvage CSI dose of 36
      Gy, delivered using IMRT and 36 Gy using electrons or photons to the spine,
      proved effective in providing good control of the disease. CONCLUSIONS: This
      technique of salvage CSI was effective in this patient cohort for leptomeningeal
      dissemination occurring outside of an area of focal irradiation. The technique
      was well tolerated and thus far has not been associated with any significant
      toxicity. Salvage therapy has been effective in 4 of the 6 patients thus far.

PMID- 24674189
TI  - Neoadjuvant chemoradiation followed by interstitial prostate brachytherapy for
      synchronous prostate and rectal cancer.
AB  - PURPOSE: To describe outcomes with the use of neoadjuvant pelvic chemoradiation
      followed by prostate interstitial brachytherapy for the treatment of synchronous
      prostate and rectal cancers. METHODS AND MATERIALS: An Internal Review Board
      approved retrospective review was undertaken of 4 patients with synchronous
      prostate and rectal cancer treated between 2006 and 2008. Patients underwent
      pelvic chemoradiation followed by prostate brachytherapy, then low anterior
      resection of the rectum with diverting loop ileostomy and adjuvant chemotherapy.
      Follow-up evaluation included imaging and laboratory analysis of cancer markers
      in addition to routine interval history and physical examination. RESULTS: At 38
      62 months postdiagnosis (24-53 months post-treatment), 6 of 8 cancers remained
      without evidence of relapse. One patient had rising carcinoembryonic antigen
      levels but no clinically evident rectal cancer relapse; another developed bony
      metastasis of his high-risk prostate cancer. Three patients experienced grade 1-2
      treatment-related toxicity; one patient had grade 3 gastrointestinal toxicity
      from radiation and surgery, which precluded his receiving adjuvant chemotherapy
      and ileostomy reversal. CONCLUSIONS: Chemoradiation followed by prostate
      brachytherapy, surgery, and adjuvant chemotherapy may be utilized to manage
      patients with synchronous prostate and rectal cancers.

PMID- 24674190
TI  - Determination of planning target volume for whole stomach irradiation using daily
      megavoltage computed tomographic images.
AB  - PURPOSE: Whole stomach radiation therapy is often used in the management of
      gastric lymphoma. However, very limited data exist with regard to planning target
      volume requirements for the whole stomach. This study retrospectively analyzed
      daily megavoltage computed tomographic (CT) scans of gastric lymphoma patients in
      order to help determine the interfraction variation of the stomach position.
      METHODS AND MATERIALS: Forty-one daily megavoltage CT images from 3 gastric
      lymphoma patients were used for stomach contouring. Each patient's megavoltage CT
      images were rigidly registered to their CT simulation data sets, and the margin
      in each direction that covered at least 95% of the daily stomach volumes was
      computed using a simple grid search. Patient setup variation was also calculated
      from the daily patient shifts. The organ motion margin was then added to the
      setup margin to render the total margin. RESULTS: A uniform margin of 2.2 cm is
      required to cover 95% of the stomach over the treatment course. However,
      direction-specific margins were observed from 1.72, 1.88, 0.92, 2.23, 1.90, and
      0.86 cm for the right, left, posterior, anterior, superior, and inferior
      directions, respectively. CONCLUSIONS: The results of this study provide helpful
      3-dimensional volumetric information to the limited existing data on margin
      requirements for whole stomach radiation therapy.

PMID- 24674191
TI  - Prevalence and significance of subcentimeter hepatic lesions in patients with
      localized pancreatic adenocarcinoma.
AB  - PURPOSE: To determine the prevalence and significance of incidental,
      subcentimeter hepatic lesions in patients with a new diagnosis of pancreatic
      cancer. MATERIALS AND METHODS: This Institutional Review Board-approved
      retrospective study included 101 patients [45% men, median age 63 years (34-85)]
      treated for localized pancreatic adenocarcinoma at Brigham and Women's Hospital
      and Dana Farber Cancer Institute from January 1999 to December 2007. Initial
      staging and follow-up computed tomographic scans were reviewed to determine the
      frequency of liver lesions that were initially too small to characterize and
      later proved to be metastases. Clinical variables known to be prognostic for
      patients with pancreatic cancer were also recorded. Using Cox regression, we
      calculated adjusted hazard ratios to determine the association between presence
      of liver lesions and overall survival. RESULTS: A total of 31 patients (30.7%)
      had subcentimeter hepatic lesions on staging scans. Of these patients, 21 (20.7%
      of total, 67.7% of patients with lesions) had eventual metastases to the liver.
      Finally, of this group, 5 patients (5.0% of total, 16.1% of patients with
      lesions) eventually had a metastatic focus at the specific site of the original
      lesion. Liver lesions predicted the occurrence of metastatic disease to the liver
      compared with patients without lesions (67.7% with lesions vs 44.4% without, P =
      .034). The presence of subcentimeter liver lesions at diagnosis was significantly
      associated with reduced overall survival (hazard ratio 1.65; 95% confidence
      interval 1.03-2.64, P = .036). CONCLUSIONS: Subcentimeter lesions in the liver
      are common in patients with a new diagnosis of pancreatic cancer. Approximately
      16% of these lesions represent metastases. The presence of indeterminate liver
      lesions may be associated with reduced overall survival.

PMID- 24674192
TI  - The efficacy of external beam radiotherapy and stereotactic body radiotherapy for
      painful spinal metastases from renal cell carcinoma.
AB  - PURPOSE: Palliative radiotherapy is routinely used to treat painful spinal
      metastases from renal cell carcinoma (RCC). Conventionally planned external beam
      radiotherapy (CRT) has been standard, with high-dose stereotactic body
      radiotherapy (SBRT) becoming increasingly common given the radioresistant nature
      of RCC. We compared the efficacy and durability of pain relief produced by these
      2 modalities. METHODS AND MATERIALS: Patients with painful spinal metastases from
      RCC treated from 2002-2010 were included. Response was defined similar to the
      Radiation Therapy Oncology Group 0631 protocol: complete response (CR) being
      resolution of pain without increased narcotics; partial response (PR) included
      patients with an incomplete reduction in pain without increased narcotics.
      Patients who experienced a CR or PR were coded as having pain relief, while those
      with persistent pain or additional narcotics requirements were coded as failures.
      Achievement of pain relief was analyzed using competing risk analysis with death
      as the competing event. Time to pain relief was plotted using cumulative
      incidence analysis. RESULTS: A total of 110 patients (34 CRT; 76 SBRT) were
      included. Median follow-up was 4.3 months (range, 0.2-38). Median Karnofsky
      performance score was higher for patients treated with SBRT compared with CRT (80
      vs 70; P = .0004). Overall pain response rates were 68% for CRT and 62% for SBRT,
      with respective CR and PR rates of 12% and 56% for CRT, and 33% and 29% for SBRT
      (P = .01). Median time to pain relief was 0.6 weeks for CRT versus 1.2 weeks for
      SBRT (P = .29). For patients who achieved pain relief (n = 79), median duration
      was 1.7 months for CRT versus 4.8 months for SBRT (P = .095). On univariate
      analysis no factors were significantly related to pain relief. CONCLUSIONS: CRT
      was not statistically different than SBRT for pain relief in symptomatic spine
      metastases from RCC and should be used as first line treatment. The appropriate
      use of SBRT in this population merits prospective study.

PMID- 24674207
TI  - Monitoring gluten-free diet in coeliac patients with Down's syndrome.

PMID- 24674208
TI  - Proceedings from the Society of Interventional Radiology Foundation Research
      Consensus Panel on Renal Sympathetic Denervation.

PMID- 24674209
TI  - Did renal artery stent placement fail in the Cardiovascular Outcomes with Renal
      Atherosclerotic Lesions (CORAL) study or did the CORAL Study Fail Renal Artery
      Stent Placement? The CORAL roll-in experience and the CORAL trials.

PMID- 24674212
TI  - Hemosuccus pancreaticus.

PMID- 24674213
TI  - US-guided placement and tip position confirmation for lower-extremity central
      venous access in neonates and infants with comparison versus conventional
      insertion.
AB  - PURPOSE: To describe experience with the use of ultrasound (US)-guided placement
      and tip position confirmation for direct saphenous and single-incision tunneled
      femoral noncuffed central venous catheters (CVCs) placed in neonates and infants
      at the bedside. MATERIALS AND METHODS: A retrospective review of the
      interventional radiology (IR) database and electronic medical records was
      performed for 68 neonates and infants who received a CVC at the bedside and for
      70 age- and weight-matched patients with CVCs placed in the IR suite between 2007
      and 2012. Technical success, complications, and outcomes of CVCs placed at the
      bedside were compared with those in an age- and weight-matched sample of children
      with CVCs placed in the IR suite. RESULTS: A total of 150 primary insertions were
      performed, with a technical success rate of 100%. Total catheter lives for CVCs
      placed at the bedside and in the IR suite were 2,030 catheter-days (mean, 27.1 d)
      and 2,043 catheter-days (mean, 27.2 d), respectively. No significant difference
      was appreciated between intraprocedural complications, mechanical complications
      (bedside, 1.53 per 100 catheter-days; IR, 1.76 per 100 catheter-days), or
      infectious complications (bedside, 0.39 per 100 catheter-days; IR, 0.34 per 100
      catheter-days) between groups. CONCLUSIONS: US-guided placement and tip position
      confirmation of lower-extremity CVCs at bedside for critically ill neonates and
      infants is a safe and feasible method for central venous access, with similar
      complications and catheter outcomes in comparison with CVCs placed by using
      fluoroscopic guidance in the IR suite.

PMID- 24674214
TI  - Externalization of tunneled hemodialysis catheter in patients with tunnel or exit
      site infections and limited access options.
AB  - PURPOSE: To evaluate the viability and effectiveness of temporary externalization
      of a tunneled hemodialysis (HD) catheter in catheter-dependent HD patients
      presenting with catheter-related tunnel or exit-site infection, documented
      central venous stenosis, and limited alternative venous access. MATERIALS AND
      METHODS: All catheter-dependent HD patients with known central venous stenosis
      presenting with exit-site or tunnel infection and who subsequently underwent
      catheter externalization between February 2008 and May 2012 were reviewed. After
      catheter externalization, patients were concurrently treated with antibiotics for
      approximately 3 weeks before reinsertion of a new tunneled catheter. Treatment
      outcomes were collected, with treatment failures defined as reinfection with the
      same organism within 45 days of tunneled catheter reinsertion. RESULTS: There
      were 42 catheter externalization procedures performed in 26 patients for 42 exit
      site or tunnel infections. Technical success rate for catheter externalization
      was 100%, with no complications during the externalization procedure and
      preservation of all original access sites. Treatment failure occurred in 9.8% (4
      of 41) of cases. Median infection-free survival after treatment and retunneling
      of a new dialysis catheter was 80 days. One major periprocedural complication of
      death occurred before reinsertion of a new tunneled catheter. Minor complications
      after the procedure occurred in four patients and included three cases of a small
      persistent wound at the temporary supraclavicular access site and one initially
      nonfunctioning externalized catheter. CONCLUSIONS: Temporary dialysis catheter
      externalization appears both technically feasible and effective for the treatment
      of exit-site and tunnel infections, while allowing preservation of the venous
      access site in catheter-dependent HD patients with central venous stenosis and
      limited alternative venous access.

PMID- 24674215
TI  - The importance of the value proposition for IR.

PMID- 24674217
TI  - Endovascular balloon-assisted embolization of high-flow peripheral vascular
      lesions using dual-lumen coaxial balloon microcatheter and Onyx: initial
      experience.
AB  - Balloon-assisted embolization performed by delivering Onyx ethylene vinyl alcohol
      copolymer through a dual-lumen coaxial balloon microcatheter is a new technique
      for the management of peripheral vascular lesions. This technique does not
      require an initial reflux of Onyx to form around the tip of the microcatheter
      before antegrade flow of Onyx can commence. In a series of four patients who were
      treated with the use of this technique, the absence of significant reflux of Onyx
      was noted, as were excellent navigability and easy retrieval of the balloon
      microcatheter. However, in one patient, there was inadvertent adverse
      embolization of a digital artery, which was not caused by reflux of Onyx but
      could still be related to balloon inflation. 

PMID- 24674218
TI  - Early initiation of enteral feeding in cancer patients after outpatient
      percutaneous fluoroscopy-guided gastrostomy catheter placement.
AB  - PURPOSE: To report the results of early enteral feeding in patients with cancer
      after outpatient placement of a percutaneous fluoroscopy-guided gastrostomy
      (PFG). MATERIALS AND METHODS: From January 2008 through December 2008, 121
      consecutive patients with cancer underwent outpatient placement of a PFG for
      nutrition. Of these patients, 118 patients met criteria for early feeding, and
      113 were successfully fed early (after at least 3 hours). Of the patients fed
      early, 5 had insufficient follow-up for further analysis leaving 108 patients for
      outcomes analysis. After placement of the PFG, patients were put on low-wall
      suction via the PFG for 1 hour followed by feeding via the PFG at least 3 hours
      after placement. Follow-up evaluation was done the next business day. The medical
      records were reviewed for 30-day outcomes of early feeding, technical aspects of
      the procedures, and complications. RESULTS: After placement of the PFG, 98% (118
      of 121) of patients met criteria for early feeding, and 93% (113 of 121) of
      patients were successfully fed early. The median time between the end of the
      procedure and initiation of feeding was 4 hours (interquartile range, 3.7-4.4 h).
      The 30-day minor complication rate was 14% (15 of 108), and the 30-day major
      complication rate was 1% (1 of 108). No complications were directly attributable
      to early feeding. CONCLUSIONS: Early initiation of tube feedings after outpatient
      placement of a PFG was well tolerated in patients with cancer and carried
      comparable risks to previously reported results using traditional delayed feeding
      protocols. Early feeding provided patients with prompt enteral nutrition and
      eliminated the need for routine hospital admission after the procedure.

PMID- 24674219
TI  - Aspiration therapy for acute superior mesenteric artery embolism with an angled
      guiding sheath and guiding catheter.
AB  - Seven patients with superior mesenteric artery embolism were treated by
      aspiration with the use of a 6-F angled guiding sheath and a 6-F guiding catheter
      through an 8-F short sheath by direct advancement using a telescopic and "biting
      off" technique. Aspiration of the trunk took between 30 and 60 minutes (median,
      44.0 min), and total procedure time ranged from 34 to 94 minutes (median, 60
      min). Five of six trunk lesions and six of nine branch lesions were successfully
      aspirated. One dissection was observed. Six patients underwent bowel resection.
      Two patients died and the remaining five survived for a median of 868.2 days
      without complications.

PMID- 24674220
TI  - Closure of the axillary artery puncture site with StarClose system after
      endovascular interventions.
AB  - The use of the StarClose vascular closure device for puncture site hemostasis
      after therapeutic endovascular interventions performed through the axillary
      artery under anticoagulant therapy in six patients is reported. Three minor
      complications, including hematoma, prolonged hemostasis, and pain, occurred in
      three patients. Based on this limited experience, this method can be used safely
      for axillary artery puncture site hemostasis after endovascular procedures
      without significant complications. 

PMID- 24674221
TI  - Image-guided sharp recanalization of a benign J pouch anastomotic occlusion
      facilitates surgical repair.
AB  - A 27-year-old man with a 9-year history of ulcerative colitis who had undergone
      total proctocolectomy with construction of a continent pouch in 2008 presented 1
      year later with occlusion of the ileal pouch-anal anastomosis precluding
      ileostomy closure. An attempt at surgical reconstruction at an outside hospital
      failed, and the patient was informed that he would have a permanent stoma. A
      further attempt at blind surgical recanalization of the occlusion risked
      sphincter damage and was deferred. In 2010, reconstruction was performed using a
      hybrid approach combining image-guided sharp recanalization of the occluded
      anastomosis with positioning of a large-diameter Foley balloon catheter across
      the recanalized segment, followed by immediate surgical revision of the J pouch.
      Ileostomy closure was performed 1 month later. Continence was preserved. Surgical
      repair preceded by sharp recanalization with positioning of a balloon catheter
      across the occluding membrane may safely regain durable patency in a chronically
      occluded ileal pouch-anal anastomosis. 

PMID- 24674222
TI  - Totally percutaneous rendezvous techniques for the treatment of bile strictures
      and leakages.
AB  - Some challenging pathologic conditions of the biliary tract cannot be treated
      with endoscopy alone, and a combined approach with rendezvous techniques is
      frequently needed. Three different totally percutaneous rendezvous techniques
      were successfully applied in three cases. The rendezvous techniques were
      performed either with bilateral catheterization of bile ducts to treat a
      challenging type IV biliary stenosis and iatrogenic biliary damage or with
      biliary catheterization and percutaneous puncture of the anastomotic loop to
      treat a biliodigestive anastomosis failure with bile leakage. 

PMID- 24674223
TI  - Extrahepatic biloma--potential imaging pitfall with "no-touch" wedge ablation of
      subcapsular liver tumors.

PMID- 24674224
TI  - Surgical repair of postoperative lymphoceles in cardiac transplant patients
      following inguinal lymphangiography with methylene blue dye injection.

PMID- 24674225
TI  - Re: does polyvinyl alcohol particle size change the outcome of prostatic arterial
      embolization for benign prostatic hyperplasia? Results from a single-center
      randomized prospective study.

PMID- 24674226
TI  - Response to "does polyvinyl alcohol particle size change the outcome of prostatic
      arterial embolization for benign prostatic hyperplasia? Results from a single
      center randomized prospective study".

PMID- 24674228
TI  - The moderating impact of self-esteem on self-affirmation effects.
AB  - OBJECTIVES: This study explored whether self-esteem would moderate the
      effectiveness of a self-affirmation manipulation at increasing openness to
      personally relevant health-risk information. DESIGN: The study employed a
      prospective experimental design. METHOD: Participants (N = 328) completed either
      a self-affirmation manipulation or a control task, prior to reading information
      detailing the health-related consequences of taking insufficient exercise. They
      then completed a series of measures assessing their cognitions towards exercise
      and their derogation of the information. Exercise behaviour was assessed at 1
      week follow-up. RESULTS: Self-esteem moderated the impact of self-affirmation on
      the majority of outcomes. For participants with low self-esteem, the self
      affirmation manipulation resulted in more positive attitudes and intentions
      towards exercise, together with lower levels of derogation of the health-risk
      information. By contrast, there was no effect of the self-affirmation
      manipulation on outcomes for participants with high self-esteem. CONCLUSION:
      Findings suggest that self-affirmation manipulations might be of particular
      benefit for those with low self-esteem in terms of promoting openness towards
      health-risk information. This is promising from a health promotion perspective,
      as individuals with low self-esteem often represent those most in need of
      intervention. Statement of contribution What is already known on this subject?
      Self-affirmation has been shown to result in more open processing of personally
      relevant health-risk information. Individuals low in self-esteem tend to process
      such information more defensively than those high in self-esteem. What does this
      study add? It explores whether self-esteem moderates the impact of self
      affirmation on responses to health-risk information. Findings suggest that
      individuals with low self-esteem benefit most from the self-affirmation
      manipulation. This has important applied implications, as individuals with low
      self-esteem may be most in need of intervention.

PMID- 24674227
TI  - Sensory trait variation in an echolocating bat suggests roles for both selection
      and plasticity.
AB  - BACKGROUND: Across heterogeneous environments selection and gene flow interact to
      influence the rate and extent of adaptive trait evolution. This complex
      relationship is further influenced by the rarely considered role of phenotypic
      plasticity in the evolution of adaptive population variation. Plasticity can be
      adaptive if it promotes colonization and survival in novel environments and in
      doing so may increase the potential for future population differentiation via
      selection. Gene flow between selectively divergent environments may favour the
      evolution of phenotypic plasticity or conversely, plasticity itself may promote
      gene flow, leading to a pattern of trait differentiation in the presence of gene
      flow. Variation in sensory traits is particularly informative in testing the role
      of environment in trait and population differentiation. Here we test the
      hypothesis of 'adaptive differentiation with minimal gene flow' in resting
      echolocation frequencies (RF) of Cape horseshoe bats (Rhinolophus capensis)
      across a gradient of increasingly cluttered habitats. RESULTS: Our analysis
      reveals a geographically structured pattern of increasing RF from open to highly
      cluttered habitats in R. capensis; however genetic drift appears to be a minor
      player in the processes influencing this pattern. Although Bayesian analysis of
      population structure uncovered a number of spatially defined mitochondrial groups
      and coalescent methods revealed regional-scale gene flow, phylogenetic analysis
      of mitochondrial sequences did not correlate with RF differentiation. Instead,
      habitat discontinuities between biomes, and not genetic and geographic distances,
      best explained echolocation variation in this species. We argue that both
      selection for increased detection distance in relatively less cluttered habitats
      and adaptive phenotypic plasticity may have influenced the evolution of matched
      echolocation frequencies and habitats across different populations. CONCLUSIONS:
      Our study reveals significant sensory trait differentiation in the presence of
      historical gene flow and suggests roles for both selection and plasticity in the
      evolution of echolocation variation in R. capensis. These results highlight the
      importance of population level analyses to i) illuminate the subtle interplay
      between selection, plasticity and gene flow in the evolution of adaptive traits
      and ii) demonstrate that evolutionary processes may act simultaneously and that
      their relative influence may vary across different environments.

PMID- 24674229
TI  - Developing an information leaflet on 22q11.2 deletion syndrome for parents to use
      with professionals during healthcare encounters.
AB  - PURPOSE: The purpose of this project was to gather parents' expertise to inform
      an educational leaflet for parents to share with professionals caring for
      children with 22q11.2 deletion syndrome (22q11.2 DS). DESIGN AND METHODS: A mixed
      method design was adopted. Data were collected by one focus group interview (n =
      8) and questionnaires with 92 other parents of children with 22q11.2 DS. RESULTS:
      Quantitative and qualitative responses informed the development of an information
      leaflet. PRACTICE IMPLICATIONS: Parents are well positioned to assist in
      development of information leaflets that can minimize "repeated storytelling"
      during professional encounters.

PMID- 24674230
TI  - Incorporation of flurbiprofen in a 4-drug cytochrome p450 phenotyping cocktail.

PMID- 24674231
TI  - Describing socioeconomic gradients in children's diets - does the socioeconomic
      indicator used matter?
AB  - BACKGROUND: Children of low socioeconomic position (SEP) generally have poorer
      diets than children of high SEP. However there is no consensus on which SEP
      variable is most indicative of SEP differences in children's diets. This study
      investigated associations between diet and various SEP indicators among children
      aged 9-13 years. METHOD: Families (n=625) were recruited from 27 Adelaide primary
      schools in 2010. Children completed semi-quantitative food frequency
      questionnaires providing intake scores for fruit, vegetables, non-core foods,
      sweetened drinks, and healthy and unhealthy eating behaviours. Parents reported
      demographic information by telephone interview. Differences in dietary intake
      scores were compared across parental education, income, occupation, employment
      status and home postcode. RESULTS: Across most SEP indicators, lower SEP was
      associated with poorer dietary outcomes, including higher intake of non-core
      foods and sweetened drinks, and more unhealthy behaviours; and lower intake of
      fruit and vegetables, and fewer healthy behaviours. The number and type of
      significant SEP-diet associations differed across SEP indicators and dietary
      outcomes. Mother's education appeared most frequently as a predictor of
      children's dietary intake, and postcode was the least frequent predictor of
      children's dietary intake. CONCLUSION: Socioeconomic gradients in children's
      dietary intake varied according to the SEP indicator used, suggesting indicator
      specific pathways of influence on children's dietary intake. Researchers should
      consider multiple indicators when defining SEP in relation to children's eating.

PMID- 24674232
TI  - Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification
      of altered cell-cycle dynamics due to ARID1B haploinsufficiency.
AB  - BACKGROUND: Mutations in genes encoding components of the Brahma-associated
      factor (BAF) chromatin remodeling complex have recently been shown to contribute
      to multiple syndromes characterised by developmental delay and intellectual
      disability. ARID1B mutations have been identified as the predominant cause of
      Coffin-Siris syndrome and have also been shown to be a frequent cause of
      nonsyndromic intellectual disability. Here, we investigate the molecular basis of
      a patient with an overlapping but distinctive phenotype of intellectual
      disability, plantar fat pads and facial dysmorphism. METHODS/RESULTS: High
      density microarray analysis of the patient demonstrated a heterozygous deletion
      at 6q25.3, which resulted in the loss of four genes including AT Rich Interactive
      Domain 1B (ARID1B). Subsequent quantitative real-time PCR analysis revealed
      ARID1B haploinsufficiency in the patient. Analysis of both patient-derived and
      ARID1B knockdown fibroblasts after serum starvation demonstrated delayed cell
      cycle re-entry associated with reduced cell number in the S1 phase. Based on the
      patient's distinctive phenotype, we ascertained four additional patients and
      identified heterozygous de novo ARID1B frameshift or nonsense mutations in all of
      them. CONCLUSIONS: This study broadens the spectrum of ARID1B associated
      phenotypes by describing a distinctive phenotype including plantar fat pads but
      lacking the hypertrichosis or fifth nail hypoplasia associated with Coffin-Siris
      syndrome. We present the first direct evidence in patient-derived cells that
      alterations in cell cycle contribute to the underlying pathogenesis of syndromes
      associated with ARID1B haploinsufficiency.

PMID- 24674233
TI  - Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin
      induced oxidative stress.
AB  - BACKGROUND: cis-Diammineplatinum (II) dichloride (cisplatin) is the important
      anti-cancer agent useful in treatment of various cancers. Unfortunately, it can
      produce unwanted side effects in various tissues, including the liver. The
      present study investigated the possible protective role of curcumin and alpha
      tocopherol against oxidative stress-induced hepatotoxicity in rats upon cisplatin
      treatment. METHODS: Male Wistar rats were divided into five groups (n = 5).
      Saline and Cis groups, rats were intraperitoneal (i.p.) injected with normal
      saline and cisplatin [20 mg/kg body weight (b.w.)], respectively. Cis + alpha
      tocopherol group, Cis + Cur group and Cis + alpha-tocopherol + Cur group, rats
      were pre-treated with a single dose of alpha-tocopherol (250 mg/kg b.w.),
      curcumin (200 mg/kg b.w.) and combined alpha-tocopherol with curcumin,
      respectively, for 24 h prior the administration of cisplatin. After 72 h of first
      injection, specimens were collected. Liver enzyme, lipid peroxidation biomarker,
      liver histopathology and gene expression of liver nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase were investigated. RESULTS: Cisplatin
      revealed a significant increase of hepatic malondialdehyde (MDA) levels and a
      significant reduction of hepatic superoxide dismutase (SOD) and catalase
      activities compared to the saline group. It elicited a marked increase of the
      serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels
      and demonstrated the liver pathologies including liver congestion,
      disorganization of hepatic cords and ground glass appearance of hepatocytes. It
      also demonstrated a significant increase of NADPH oxidase gene expression
      compared to saline group. Pre-treatment with combined curcumin and alpha
      tocopherol improved the liver enzymes, lipid peroxidation biomarker, liver
      histopathology and gene expression of liver NADPH oxidase in cisplatin-treated
      rats. CONCLUSIONS: The findings indicate that pre-treatment with combined
      curcumin and alpha-tocopherol can protect cisplatin-induced hepatotoxicity
      including the biochemical, histological and molecular aspects. The down
      regulations of NADPH oxidase gene expression may be involved in abrogating
      oxidative stress via reduction of reactive oxygen species (ROS) production.

PMID- 24674234
TI  - An evaluation of hepatic enzyme elevations among HIV-infected released prisoners
      enrolled in two randomized placebo-controlled trials of extended release
      naltrexone.
AB  - Extended-release naltrexone (XR-NTX), an approved treatment for opioid or alcohol
      dependence, is a once-monthly injectable formulation of naltrexone.
      Hepatotoxicity concerns have limited its use, necessitating further
      investigation. This study aims to examine hepatic enzyme levels in participants
      of 2 randomized placebo-controlled trials (RCTs) of XR-NTX. Hepatic transaminases
      were measured in 85 patients enrolled in RCTs of XR-NTX among HIV-infected
      prisoners, transitioning to the community and receiving treatment for either
      dependence on alcohol (52.9%), opioids (44.7%) or both (16.5%). Baseline
      characteristics included HCV co-infection (55.7%), antiretroviral therapy (81%),
      mental illness (39%) and receiving psychiatric medications (34.1%). Levels of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma
      glutamyl transferase (GGT) were not statistically different between persons
      randomized to placebo (N=24) and XR-NTX (N=61) arms. These results confirm that
      XR-NTX is safe to use among opioid and alcohol dependent HIV-infected released
      prisoners receiving ART with high rates of co-morbid HCV infection and mental
      illness. 

PMID- 24674236
TI  - NPHS2 mutation analysis and primary nephrotic syndrome in southern Indians.
AB  - AIM: Nephrotic syndrome is one of the most commonly diagnosed primary kidney
      diseases and its progressive forms can lead to chronic kidney disease and or end
      stage renal disease. Steroid-resistant nephrotic syndrome is defined by
      resistance to standard steroid therapy and it remains one of the most intractable
      causes of kidney failure. Mutations in NPHS2, which encodes for podocin, an
      integral membrane protein of the glomerular epithelial cells (podocytes),
      represent a frequent cause of steroid-resistant nephrotic syndrome worldwide.
      This study was aimed at screening for known NPHS2 mutations in Indians with
      nephrotic syndrome. METHODS: We screened a cohort of 484 subjects from the
      southern Indian population for the presence of four missense mutations G92C,
      P118L, R138Q and D160G within the NPHS2 gene using tetra primer ARMS PCR.
      RESULTS: Our results revealed that these mutations were seen only among the
      patients (14.02%) and were absent in the controls, suggesting their disease
      causing nature. Further categorization revealed that these mutations were
      together responsible for 18.5% of steroid-resistant cases in our study group.
      Conversely, the studied mutations were not found in the controls as well as in
      the patients with steroid-sensitive nephrotic syndrome. CONCLUSION: This is the
      first such report from India. More studies are warranted to establish the
      frequency of NPHS2 mutations in the Asian-Indian population and such analysis may
      help in developing mutation(s)-specific therapeutic interventions in the future.

PMID- 24674235
TI  - Contingency management voucher redemption as an indicator of delayed
      gratification.
AB  - This prospective analysis tested whether frequency of voucher redemptions during
      a contingency management (CM) substance use intervention was significantly
      associated with participants' ongoing substance use. Homeless, substance
      dependent men who have sex with men (N=131) were randomized into either a "full"
      or "lite" voucher-based CM intervention. All participants earned vouchers for
      attendance and participation; participants in the CM-full condition also received
      vouchers for substance abstinence and enactment of prosocial and/or health
      promoting behaviors. Multivariate longitudinal negative binomial regression
      analyses (n=118) assessed the association between substance use during the
      intervention and frequency of voucher redemptions. Participants who used
      methamphetamine (IRR=0.66; 95% CI=0.44-0.99) and/or opiates (IRR=0.60; 95%
      CI=0.40-0.99) during the intervention exhibited less time between voucher
      redemptions than individuals who achieved abstinence from these substances.
      Voucher redemption logs can be cost-effective and unobtrusive tools for measuring
      study participants' tendency to delay gratification. 

PMID- 24674237
TI  - IGF-I and NEFA concentrations in fetal fluids of term pregnancy dogs.
AB  - Insulin-like growth factor-I (IGF-I) and non-esterified fatty acids (NEFA) play
      an essential role in fetal growth and development. To date, fetal fluids IGF-I
      and NEFA levels at term canine pregnancy are unknown and could be related to the
      neonatal development and breed size. For these reasons, the aims of the present
      study were as follows: (1) to evaluate IGF-I and NEFA concentrations in fetal
      fluids collected from normally developed and viable newborn puppies born at term
      of normal pregnancies; (2) to assess possible differences between IGF-I and NEFA
      levels in amniotic compared with allantoic fluid; (3) to detect possible
      relationship between breed body size and IGF-I and NEFA amniotic and allantoic
      concentrations; (4) to evaluate possible differences in IGF-I fetal fluids levels
      between male and female puppies; and (5) to assess possible correlations between
      the two hormones in each type of fluid. The study enrolled 25 pure breed bitches
      submitted to elective Cesarean section at term because of the high risk of
      dystocia or previous troubles at parturition. At surgery, amniotic and allantoic
      fluids were collected and assayed for IGF-I and NEFA. IGF-I and NEFA amounts in
      both amniotic and allantoic fluids of different breed size bitches (small: <=10
      kg; medium: 11-25 kg; large: 26-40 kg) were detected, as well as the effect of
      gender on IGF-I levels. On a total of 73 amniotic and 76 allantoic samples
      collected by normal, viable, and mature newborns, the mean IGF-I concentration
      was significantly higher in amniotic than in allantoic fluid in all three groups,
      but the amniotic IGF-I levels were significantly lower in small and medium size
      bitches when compared with large ones. No significant differences were found in
      allantoic IGF-I concentrations among size groups. A significant effect of the
      puppy gender on IGF-I content in both fetal fluids was not reported. Regarding
      NEFA, in all the three groups, the mean NEFA concentration did not significantly
      differ between amnion and allantois, but in both fetal fluids, higher NEFA levels
      were detected in samples belonging to small breeds when compared with medium and
      large. These data strongly indicated that, also in the dog, a relation between
      fetal fluids IGF-I and NEFA concentrations and breed size exists. Further
      research is needed to elucidate the possible role of IGF-I and NEFA in the
      pathologic conditions related to canine fetal growth.

PMID- 24674238
TI  - Management and outcomes of acute appendicitis in pregnancy-population-based study
      of over 7000 cases.
AB  - OBJECTIVE: To compare outcomes and management practices among pregnant and
      nonpregnant women with acute appendicitis. DESIGN: Population-based matched
      cohort study. SETTING: United States of America. SAMPLE: A total of 7114 women
      with appendicitis among 7,037,386 births. METHODS: Logistic regression analyses
      to calculate the odds ratio (OR) and corresponding 95% confidence intervals (95%
      CIs) for variables and outcomes of interest. MAIN OUTCOME MEASURES: Maternal
      morbidities associated with appendicitis; management practices for pregnant and
      age-matched nonpregnant women with appendicitis. RESULTS: There was an overall
      incidence of 101.1 cases of appendicitis per 100,000 births. Appendicitis was
      diagnosed in 35,570 nonpregnant women during the corresponding time frame.
      Peritonitis occurred in 20.3% of pregnant women with appendicitis, with an
      adjusted OR of 1.3 (95% CI 1.2-1.4) when compared with nonpregnant women with
      appendicitis. In pregnancy, there was an almost two-fold increase in sepsis and
      septic shock, transfusion, pneumonia, bowel obstruction, postoperative infection
      and length of stay >3 days. Whereas 5.8% of appendicitis cases among pregnant
      women were managed conservatively, they were associated with a considerably
      increased risk of shock, peritonitis and venous thromboembolism as compared to
      surgically managed cases. CONCLUSIONS: Compared with nonpregnant women, pregnant
      women with acute appendicitis have higher rates of adverse outcomes. Conservative
      management should be avoided given the serious risk of adverse outcomes in
      pregnancy.

PMID- 24674239
TI  - Anxiety, worry and cognitive risk estimate in relation to protective behaviors
      during the 2009 influenza A/H1N1 pandemic in Hong Kong: ten cross-sectional
      surveys.
AB  - BACKGROUND: Few studies have investigated associations between psychological and
      behavioral indices throughout a major epidemic. This study was aimed to compare
      the strength of associations between different cognitive and affective measures
      of risk and self-reported protective behaviors in a series of ten cross-sectional
      surveys conducted throughout the first wave of influenza A/H1N1 pandemic.
      METHODS: All surveys were conducted using questionnaire-based telephone
      interviews, with random digit dialing to recruit adults from the general
      population. Measures of anxiety and worry (affective) and perceived risk
      (cognitive) regarding A/H1N1 were made in 10 serial surveys. Multivariate
      logistic regression models were used to estimate the cognitive/affective
      behavioral associations in each survey while multilevel logistic models were
      conducted to estimate the average effects of each cognitive/affective measure on
      adoption of protective behaviors throughout the ten surveys. RESULTS: Excepting
      state anxiety, other affective measures including "anticipated worry",
      "experienced worry" and "current worry" specific to A/H1N1 risk were consistently
      and strongly associated with adoption of protective behaviors across different
      survey periods. However, the cognitive-behavioral associations were weaker and
      inconsistent across the ten surveys. Perceived A/H1N1 severity relative to SARS
      had stronger associations with adoption of protective behaviors in the late
      epidemic periods than in the early epidemic periods. CONCLUSION: Risk-specific
      worries appear to be significantly associated with the adoption of protective
      behaviors at different epidemic stages, whereas cognitive measures may become
      more important in understanding people's behavioral responses later in epidemics.
      Future epidemic-related psycho-behavioral research should include more affective
      loaded measures of risk.

PMID- 24674240
TI  - Increased sensitivity of Apolipoprotein E knockout mice to swainsonine dependent
      immunomodulation.
AB  - The mechanisms that mediate accelerated atherosclerosis in autoimmune diseases
      remain unclear. One common mechanism that has been documented in autoimmune
      diseases and atherosclerosis is formation of hypoglycosyalted N-glycans on the
      cell surface. In this study we tested the effects of swainsonine, a class II
      alpha-mannosidase inhibitor which results in formation of hypoglycosylated N
      glycans, on atherogenesis and immune cell dynamics in the atheroprone and
      hypercholesterolemic ApoE -/- mouse. Wild type or ApoE-/- mice (8 weeks of age)
      were fed a normal chow diet and administered swainsonine via the drinking water
      for 8 weeks at which time, atherosclerosis, and systemic markers of markers of
      inflammation were evaluated. Interestingly, no change in the rate of
      atherosclerosis development was observed in ApoE -/- mice treated with
      swainsonine. However, swainsonine significantly increased the number of
      peripheral blood leukocytes in ApoE -/- mice, with trends toward similar
      increases in swainsonine treated wild type mice noted. Assessment of leukocyte
      subsets using specific markers of all major blood lineages indicated that the
      increase in circulating leukocytes was due to the elevated number of progenitor
      cells. Consistent with swainsonine having a greater effect in ApoE -/- vs. wild
      type mice, increases in circulating inflammatory markers (IgA, IgG and
      chemokines) were observed in the former. Collectively, these data demonstrate
      that predisposition of ApoE -/- mice to vascular disease is associated with
      sensitization to the immunomodulatory effects of swainsonine and indicate that
      changes in N-glycans may provide a mechanism linking autoimmunity to
      atherogenesis. 

PMID- 24674241
TI  - STAT3-silenced human dendritic cells have an enhanced ability to prime IFNgamma
      production by both alphabeta and gammadelta T lymphocytes.
AB  - Dendritic cells (DC) are an attractive target for therapeutic manipulation of the
      immune system to enhance insufficient immune responses, such those occurring in
      cancer, or to dampen dangerous responses in allergic and autoimmune diseases.
      Main goal of this study was to manipulate human monocyte-derived DC (MDDC)
      function by silencing STAT3, since this transcription factor plays a key role as
      a negative regulator of immune surveillance, and is strongly involved in
      inflammation. STAT3 silencing did not affect the immunophenotype of both immature
      and toll-like receptor (TLR) ligand-matured DC. However, an altered cytokine
      secretion profile, characterized by lower IL10 and higher IL12 and TNFalpha
      levels, was observed in silenced DC with respect to control cells upon TLR
      triggering. Accordingly, STAT3 silenced MDDC promoted a higher IFNgamma
      production by CD4(+) naive T cells. Furthermore, STAT3 silencing in MDDC favored
      the activation of gammadelta T lymphocytes, an immune cell population with
      important antitumor effector activities. This effect was at least in part
      mediated by the increased IL12 production by silenced cells. STAT3 silencing also
      increased the levels of CCL4, a CCR5-binding chemokine known to be involved in T
      helper 1 (Th1) cell recruitment. Altogether these results strengthen the role of
      STAT3 as a critical check point of the suppression of Th1 responses, unraveling
      its potential to dampen DC capability to both induce and recruit different
      IFNgamma producing T lymphocyte subsets. 

PMID- 24674243
TI  - Reinterpretation of radiological findings in oesophago-gastric multidisciplinary
      meetings.
AB  - BACKGROUND: This study aims to objectively evaluate the clinical impact and
      significance of the multidisciplinary team meeting (MDT) in the management of
      oesophago-gastric malignancies in a tertiary institution. METHODS: A prospective
      observational study was designed to examine the role of MDT in the interpretation
      of computerized tomography (CT) scans in oesophago-gastric malignancies. The MDT
      reporting of CT scans were compared with the 'pre-meeting' formal report of the
      scans. 'Pre-meeting' CT reports are provided by internal institutional or
      independent radiologist. The frequency and significance of any reporting variance
      is examined. RESULTS: Of the 34 patients discussed, 13 patients (38%) had
      variations to the formal radiological report. This led a modification of disease
      stage in seven patients (21%) and change in diagnosis in three patients (9%).
      This had a major impact in nine patients (26%) of which seven patients (24%) had
      modification in treatment as a result of imaging reinterpretation. CONCLUSION:
      This study provides preliminary quantative evidence of the utility and importance
      of the MDT process in the management of oesophago-gastric malignancies. This has
      potential significant implications for basing patient treatment on isolated
      reports outside of MDT and supports this process as a standard of care.

PMID- 24674242
TI  - Introgressive hybridization and latitudinal admixture clines in North Atlantic
      eels.
AB  - BACKGROUND: Hybridization, the interbreeding of diagnosably divergent species, is
      a major focus in evolutionary studies. Eels, both from North America and Europe
      migrate through the Atlantic to mate in a vast, overlapping area in the Sargasso
      Sea. Due to the lack of direct observation, it is unknown how these species
      remain reproductively isolated. The detection of inter-species hybrids in Iceland
      suggests on-going gene flow, but few studies to date have addressed the influence
      of introgression on genetic differentiation in North Atlantic eels. RESULTS:
      Here, we show that while mitochondrial lineages remain completely distinct on
      both sides of the Atlantic, limited hybridization is detectable with nuclear DNA
      markers. The nuclear hybridization signal peaks in the northern areas and
      decreases towards the southern range limits on both continents according to
      Bayesian assignment analyses. By simulating increasing proportions of both F1
      hybrids and admixed individuals from the southern to the northern-most locations,
      we were able to generate highly significant isolation-by-distance patterns in
      both cases, reminiscent of previously published data for the European eel.
      Finally, fitting an isolation-with-migration model to our data supports the
      hypothesis of recent asymmetric introgression and refutes the alternative
      hypothesis of ancient polymorphism. CONCLUSIONS: Fluctuating degrees of
      introgressive hybridization between Atlantic eel species are sufficient to
      explain temporally varying correlations of geographic and genetic distances
      reported for populations of the European eel.

PMID- 24674244
TI  - Editorial freedom: the trials and tribulations of being an editor.

PMID- 24674245
TI  - Dummy (pacifier) use and sudden infant death syndrome: potential advantages and
      disadvantages.
AB  - The large decline in deaths due to the sudden infant death syndrome (SIDS) in the
      last 20 years in many countries is largely due to risk-reduction advice resulting
      from observational studies that examined the relationship between infant care
      practices and SIDS. Most of this advice remains largely uncontroversial and
      educators and researchers in this field are in agreement as to the specific
      recommendations that should be given to parents and health professionals.
      However, advice surrounding the apparent protective effect of dummies (also known
      as pacifiers) has been controversial. Several systematic reviews have
      demonstrated a strong association between the lack of a pacifier being used by
      the infant for the final sleep and SIDS, but it is not clear how pacifiers confer
      protection or if this is a marker for something as yet unmeasured. The
      Epidemiology and Physiology Working Groups of the International Society for the
      Study and Prevention of Perinatal and Infant Death (ISPID) are comprised of
      leading SIDS researchers with an objective to provide evidence-based position
      statements surrounding the factors associated with SIDS (http://www.ispid.org/)
      and risk-reduction strategies. The evidence, discussion and conclusions from
      these working groups regarding dummies (pacifiers) are described below to help
      inform this debate and describe the future evidence required so that we might
      find a common recommendation about dummies (pacifiers) and SIDS. 

PMID- 24674250
TI  - Vesicles and crusts on photoexposed areas.

PMID- 24674251
TI  - Swearing in Dutch.

PMID- 24674252
TI  - Emotional impact of Bell's palsy in children.

PMID- 24674253
TI  - Drager Babylog 8000 plus neonatal ventilator: responses to circuit disconnection.

PMID- 24674254
TI  - The junior doctor: an untapped paediatric teaching resource?

PMID- 24674256
TI  - Interpreting medical literature: a helpful glossary.

PMID- 24674257
TI  - Editor's Note.

PMID- 24674258
TI  - Effect of bra use during radiation therapy for large-breasted women: Acute
      toxicity and treated heart and lung volumes.
AB  - PURPOSE: Large breast size presents special problems during radiation simulation,
      planning, and patient treatment, including increased skin toxicity, in women
      undergoing breast-conserving surgery and radiation therapy (BCT). We report our
      experience using a bra during radiation in large-breasted women and its effect on
      acute toxicity and heart and lung dosimetry. METHODS AND MATERIALS: From 2001 to
      2006, 246 consecutive large-breasted women (bra size >=38 or >=D cup) were
      treated with BCT using either 3-dimensional conformal radiation therapy (3DCRT)
      or intensity modulated radiation therapy (IMRT). In 58 cases, at the physicians'
      discretion, a custom-fit bra was used during simulation and treatment. Endpoints
      were acute radiation dermatitis and dosimetric comparison of heart and lung
      volumes in a subgroup of 12 left-sided breast cancer patients planned with and
      without a bra. RESULTS: The majority of acute skin toxicities were grade 2 and
      were experienced by 90% of patients in a bra compared with 70% of patients not in
      a bra (P = .003). On multivariate analysis significant predictors of grade 2 or 3
      skin toxicity included the use of 3DCRT instead of IMRT (odds ratio, 3.9; 95%
      confidence interval, 1.8-8.5) and the use of a bra (odds ratio, 5.5; 95%
      confidence interval, 1.6-18.8). For left-sided patients, the use of a bra was
      associated with a volume of heart in the treatment fields decreased by 63.4% (P =
      .002), a volume of left lung decreased by 18.5% (P = .25), and chest wall
      separation decreased by a mean of 1 cm (P = .03). CONCLUSIONS: The use of a bra
      to augment breast shape and position in large-breasted women is an alternative to
      prone positioning and associated with reduced chest wall separation and reduced
      heart volume within the treatment field.

PMID- 24674259
TI  - Clinical evaluation of interfractional variations for whole breast radiotherapy
      using 3-dimensional surface imaging.
AB  - PURPOSE: To evaluate the impact of 3-dimensional (3D) surface imaging on daily
      patient setup for breast radiotherapy. MATERIALS AND METHODS: Fifty patients
      undergoing treatment for whole breast radiotherapy were setup daily using an
      AlignRT system (VisionRT, London, UK) for 3D surface-based alignment. Daily
      alignments were performed against a reference surface topogram and shifts from
      skin marks were recorded daily. This investigation evaluated the following: (1)
      the performance of the surface-based imaging system for daily breast alignment;
      (2) the absolute displacements between setup with skin marks and setup with the
      surface-based imaging system; and (3) the dosimetric effect of daily alignments
      with skin marks versus surface-based alignments. RESULTS: Displacements from 1258
      treatment fractions were analyzed. Sixty percent of those fractions (749) were
      reviewed against MV portal imaging in order to assess the performance of the
      AlignRT system. Daily setup errors were given as absolute displacements,
      comparing setup marks against shifts determined using the surface-based imaging
      system. Averaged over all patients, the mean displacements were 4.1 +/- 2.6 mm,
      2.7 +/- 1.4 mm, and 2.6 +/- 1.2 mm in the anteroposterior (AP), superoinferior
      (S/I), and left-right (L/R) directions, respectively. Furthermore, the standard
      deviation of the random error (sigma) was 3.2 mm, 2.2 mm, and 2.2 mm in the A/P,
      S/I, and L/R directions, respectively. CONCLUSIONS: Daily alignment with 3D
      surface imaging was found to be valuable for reducing setup errors when comparing
      with patient alignment from skin marks. The result of the surface-based
      alignments specifically showed that alignment with skin marks was noticeably poor
      in the anteroposterior directions. The overall dosimetric effect of the
      interfractional variations was small, but these variations showed a potential for
      increased dose deposition to both the heart and lung tissues. Although these
      interfractional variations would not negatively affect the quality of patient
      care for whole breast radiotherapy, it may require an increase in PTV margin,
      especially in cases of partial breast irradiation.

PMID- 24674260
TI  - Concurrent chemotherapy and intensity modulated radiation therapy in the
      treatment of anal cancer: A retrospective review from a large academic center.
AB  - PURPOSE: To assess the toxicity and efficacy of intensity modulated radiation
      therapy (IMRT) combined with chemotherapy in treatment of anal cancer. METHODS
      AND MATERIALS: We examined the records of 34 consecutive patients who received
      chemoradiation therapy with IMRT as initial treatment for squamous cell carcinoma
      of the anus between June 2005 and January 2009. The median radiation dose was
      50.4 Gy (range, 48.6-57.6 Gy). Chemotherapy was given concurrently: 5
      fluorouracil alone in 1 patient and combination 5-fluorouracil and mitomycin C in
      all others. Endpoints included local control and survival, as well as toxicity.
      Acute and late toxicity was scored with the Common Terminology Criteria for
      Adverse Events version 3.0. RESULTS: Twenty-eight patients presented with T1 and
      T2 disease and 6 with T3 and T4 disease. Fourteen patients had regional nodal
      metastases. The median age was 59 years (range, 46-85 years). Median follow-up in
      surviving patients was 22 months. The estimated 2-year survival was 93% (95%
      confidence interval, 76%-98%). Three patients (9%) had local relapse (estimated 2
      year local control, 90%; 95% confidence interval, 74%-97%). One patient had
      relapse in a regional node. Acute grade 3-4 hematologic toxicity was observed in
      20 patients (59%). Other acute grade 3 or grade 4 toxicity included the
      gastrointestinal tract in 3 patients (9%) and skin in 5 patients (15%). Two
      patients (6%) had late grade 3 or grade 4 gastrointestinal tract toxicity.
      CONCLUSIONS: Treatment of anal squamous cell carcinoma with IMRT and chemotherapy
      is effective and has an acceptable toxicity profile.

PMID- 24674261
TI  - Stability of endoscopic ultrasound-guided fiducial marker placement for
      esophageal cancer target delineation and image-guided radiation therapy.
AB  - PURPOSE: Fiducial markers have been integrated into the management of multiple
      malignancies to guide more precise delivery of radiation therapy (RT). Fiducials
      placed at the margins of esophageal tumors are potentially useful to facilitate
      both RT target delineation and image-guided RT (IGRT). In this study, we report
      on the stability of endoscopic ultrasound (EUS)-guided fiducial placement for
      esophageal cancers and utilization for radiation treatment planning and IGRT.
      METHODS: An institutional review board-approved database was queried for patients
      treated for esophageal cancer with chemoradiotherapy (CRT). Patients included in
      the analysis had a diagnosis of esophageal cancer, were referred for treatment
      with CRT, and had fiducials placed under EUS guidance. Images acquired at time of
      radiation treatment planning, daily IGRT imaging, post-treatment restaging, and
      surveillance scans were analyzed to determine the stability of implanted markers.
      RESULTS: We identified 60 patients who underwent EUS-guided fiducial marker
      placement near the margins of their esophageal tumors in preparation for RT
      treatment planning. A total of 105 fiducial markers were placed. At time of CT
      simulation, 99 markers were visualized. Fifty-seven patients had post-treatment
      imaging available for review. Of the 100 implanted fiducials in these 57
      patients, 94 (94%) were visible at time of RT simulation. Eighty-eight (88%)
      fiducials were still present post-treatment imaging at a median of 107 days
      (range, 33-471 days) after implantation. CONCLUSIONS: EUS-guided fiducial marker
      placement for esophageal cancer aids in target delineation for radiation planning
      and daily IGRT. Fiducial stability is reproducible and facilitates conformal
      treatment with image-guided RT techniques.

PMID- 24674262
TI  - Gastric perforation following stereotactic body radiation therapy of hepatic
      metastasis from colon cancer.

PMID- 24674263
TI  - Anatomic distribution of [(18)F] fluorodeoxyglucose-avid lymph nodes in patients
      with cervical cancer.
AB  - PURPOSE: Current information about the anatomic distribution of lymph node (LN)
      metastases from cervical cancer is not precise enough for optimal treatment
      planning for highly conformal radiation therapy. To accurately define the
      anatomic distribution of these LN metastases, we mapped [(18)F]
      fluorodeoxyglucose positron emission tomography (FDG PET)-positive LNs from 50
      women with cervical cancer. METHODS AND MATERIALS: Records of patients with
      cervical cancer treated from 2006 to 2010 who had pretreatment PET/computed
      tomography (CT) scans available were retrospectively reviewed. Forty-one
      consecutive patients (group 1) with FDG-avid LNs were identified; because there
      were few positive paraortic LNs in group 1, 9 additional patients (group 2) with
      positive paraortic LNs were added. Involved LNs were contoured on individual
      PET/CT images, mapped to a template CT scan by deformable image registration, and
      edited as necessary by a diagnostic radiologist and radiation oncologists to most
      accurately represent the location on the original PET/CT scan. RESULTS: We
      identified 190 FDG-avid LNs, 122 in group 1 and 68 in group 2. The highest
      concentrations of FDG-avid nodes were in the external iliac, common iliac, and
      paraortic regions. The anatomic distribution of the 122 positive LNs in group 1
      was as follows: external iliac, 78 (63.9%); common iliac, 21 (17.2%); paraortic,
      9 (7.4%); internal iliac, 8 (6.6%); presacral, 2 (1.6%); perirectal, 2 (1.6%);
      and medial inguinal, 2 (1.6%). Twelve pelvic LNs were not fully covered when the
      clinical target volume was defined according to Radiation Therapy Oncology Group
      guidelines for intensity modulated radiation therapy for cervical cancer.
      CONCLUSIONS: Our findings clarify nodal volumes at risk and can be used to
      improve target definition in conformal radiation therapy for cervical cancer. Our
      findings suggest several areas that may not be adequately covered by contours
      described in available atlases.

PMID- 24674264
TI  - Computed tomographic atlas for the new international lymph node map for lung
      cancer: A radiation oncologist perspective.
AB  - PURPOSE: To develop a reproducible definition for each mediastinal lymph node
      station based on the new TNM classification for lung cancer. METHODS AND
      MATERIALS: This paper proposes an atlas using the new international lymph node
      map used in the seventh edition of the TNM classification for lung cancer. Four
      radiation oncologists and 1 diagnostic radiologist were involved in the project
      to put forward a reproducible radiologic description for the lung lymph node
      stations. RESULTS: The International Association for the Study of Lung Cancer
      lymph node definitions for stations 1 to 11 have been described and illustrated
      on axial computed tomographic scan images using a certified radiotherapy planning
      system. CONCLUSIONS: This atlas will assist both diagnostic radiologists and
      radiation oncologists in accurately defining the lymph node stations on computed
      tomographic scan in patients diagnosed with lung cancer.

PMID- 24674265
TI  - Required target margins for image-guided lung SBRT: Assessment of target position
      intrafraction and correction residuals.
AB  - PURPOSE: With increased use of stereotactic body radiotherapy (SBRT) for early
      stage lung cancer, quantification of intrafraction variation (IFV) is required to
      develop adequate target margins. METHODS AND MATERIALS: A total of 409 patients
      with 427 tumors underwent 1593 fractions of lung SBRT between 2005 and 2010.
      Translational target position correction of the mean target position (MTP) was
      performed via onboard cone-beam computed tomography (CBCT). IFV was measured as
      the difference in MTP between the post-correction CBCT and the post-treatment
      CBCT and was calculated on 1337 fractions. RESULTS: Mean IFV-MTP was 0.0 +/- 1.7
      mm, 0.6 +/- 2.2 mm, and -1.0 +/- 2.0 mm in the mediolateral (ML), anteroposterior
      (AP), and craniocaudal (CC) dimensions, and the vector was 3.1 +/- 2.0 mm; 67.8%
      of fractions had an IFV vector greater than 2 mm, and 14.3% greater than 5 mm.
      Weight, excursion, forced expiratory volume in the first second of expiration,
      diffusing capacity of the lung for carbon monoxide, and treatment time were found
      to be significant predictors of IFV-MTP greater than 2 mm and 5 mm. Significant
      differences in IFV-MTP were seen between immobilization devices with a mean IFV
      of 2.3 +/- 1.4 mm, 2.7 +/- 1.6 mm, 3.0 +/- 1.7 mm, 3.0 +/- 2.5 mm, 3.3 +/- 1.7
      mm, and 3.3 +/- 2.2 mm for the body frame, hybrid device, alpha cradle, body fix,
      wing board, and no immobilization, respectively (P < .001). Estimated required
      target margins for the entire cohort were 4.3, 6.1, and 6.0 mm in the ML, AP, and
      CC dimensions, with differences in margins based on immobilization. CONCLUSIONS:
      IFV is dependent on several factors: immobilization device, treatment time,
      pulmonary function, and bodyweight. These factors are responsible for a
      significant portion of target margins with a mean IFV vector of 3 mm. Target
      margins of 6 mm or greater are required to encompass IFV in all dimensions when
      using four-dimensional CT with CBCT without respiratory gating or compression.

PMID- 24674266
TI  - Reliability of oral examinations: Radiation oncology certifying examination.
AB  - PURPOSE: Oral examinations are used in certifying examinations by many medical
      specialty boards. They represent daily clinical practice situations more
      realistically than do written tests or computer-based tests. However, there are
      repeated concerns in the literature regarding objectivity, fairness, and
      extraneous factors from interpersonal interactions, item bias, reliability, and
      validity. In this study, the reliability of oral examination on the radiation
      oncology certifying examination, which was administered in May of 2010, was
      analyzed. METHODS AND MATERIALS: One hundred fifty-two candidates rotated though
      8 examination stations. Stations consisted of a hotel room equipped with a
      computer and software that exhibited images appropriate to the content areas.
      Each candidate had a 25-30 minute face-to-face encounter with an oral examiner
      who was a content expert in one of the following areas: gastrointestinal,
      gynecology, genitourinary, lymphoma/leukemia/transplant/myeloma, head/neck/skin,
      breast, central nervous system/pediatrics, or lung/sarcoma. This type of design
      is typically referred to as a repeated measures design or a subject by treatment
      design, although the oral examination was a routine event without any
      experimental manipulation. RESULTS: The reliability coefficient was obtained by
      applying Feldt and Charter's simple computational alternative to analysis of
      variance formulas that yielded KR-20, or Cronbach's coefficient alpha of 0.81.
      CONCLUSIONS: An experimental design to develop a blueprint in order to improve
      the consistency of evaluation is suggested.

PMID- 24674267
TI  - Impact of magnetic resonance imaging on computed tomography-based treatment
      planning and acute toxicity for prostate cancer patients treated with intensity
      modulated radiation therapy.
AB  - PURPOSE: To evaluate rectal and bladder dosimetric and clinical acute toxicity
      endpoints for prostate patients treated with intensity modulated radiation
      therapy (IMRT) using magnetic resonance images (MRI) registered to computed
      tomographic (CT) simulation images versus CT alone. MATERIALS AND METHODS: The
      charts of 155 consecutive prostate cancer patients at our institution from 2004
      to 2008 were reviewed. A cohort of 15 IMRT treatment plans was created to compare
      dosimetric endpoints for CT-MRI vs CT alone. A subsequent clinical comparison
      involved 81 patients (CT-MRI [n = 28] vs CT alone [n = 53]). Acute genitourinary
      and rectal toxicity rates for the CT-MRI and CT cohorts were compared; also,
      univariate and multivariate regression analyses were performed using all major
      demographic, disease, and treatment factors as covariates. RESULTS: Contoured
      prostate volumes were 43.0 vs 55.7 cm(3) (P < .001, n = 15) for CT-MRI vs CT
      definition, with significant reductions in all bladder dose endpoints and rectal
      V20, V30, and V70. Grades 0, 1, and 2 toxicity rates for CT-MRI (n = 28) vs CT (n
      = 53) were, respectively, 25%, 25%, and 50% vs 8%, 21%, and 72% (acute
      genitourinary [GU], P = .024) and 39%, 29%, and 32% vs 32%, 28%, and 40% (acute
      rectal, P = .495). On univariate regression, only MRI use and International
      Prostate Symptom Scores reached significance for acute GU toxicity. On
      multivariate regression, age, prostate volume, and MRI use reached statistical
      significance for acute GU toxicity. No factor reached significance for rectal
      toxicity. CONCLUSIONS: This study demonstrates a statistically significant
      reduction in clinical acute GU toxicity with the clinical implementation of MRI
      in the treatment planning process.

PMID- 24674268
TI  - Gastric lymph node contouring atlas: A tool to aid in clinical target volume
      definition in 3-dimensional treatment planning for gastric cancer.
AB  - PURPOSE: To develop a contouring atlas of the gastric lymph node stations to be
      used in defining and planning clinical target volumes in 3-dimensional treatment
      planning for gastric cancers. METHODS AND MATERIALS: Four physicians, including 2
      radiation oncologists, a diagnostic radiologist, and a surgical oncologist
      specialized in gastric cancer, convened over the course of multiple meetings.
      Four patients were identified as representative cases, including 3 gastric cancer
      patients treated with differing surgical approaches (total gastrectomy, Ivor
      Lewis esophagogastrectomy, and distal gastrectomy) and 1 patient with intact
      gastric anatomy. Radiographic delineation of lymph node stations was established
      for each case to highlight differences between intact anatomy and different
      postoperative anatomy. RESULTS: Consensus was achieved among physicians in order
      to create a computed tomographic-based contouring atlas of gastric lymph node
      stations. Detailed radiographic lymph node station delineation for both intact
      gastric anatomy and post-surgical anatomy are discussed. CONCLUSIONS: This report
      serves as a template for the delineation of gastric lymph node stations to aid in
      the definition of elective clinical target volumes to be used in conformal
      treatment planning.

PMID- 24674269
TI  - Intensity modulated radiation therapy for definitive treatment of paraortic
      relapse in patients with endometrial cancer.
AB  - PURPOSE: The paraortic nodes are a common site of recurrence of endometrial
      cancer, especially among patients previously treated with pelvic radiation.
      Intensity modulated radiation therapy (IMRT) can be used to deliver a tumoricidal
      dose to paraortic disease while minimizing dose to normal adjacent structures. In
      this study, we reviewed the outcomes of patients treated with IMRT for unresected
      or incompletely resected paraortic recurrences of primary uterine cancer. METHODS
      AND MATERIALS: Between 2000 and 2009, 27 patients with unresected (19 patients)
      or incompletely resected (8 patients) paraortic relapse of endometrial cancer
      were treated with curative intent using IMRT. The paraortic basin was generally
      treated to a dose of 45-50 Gy, and gross disease was treated to a mean total dose
      of 61.7 Gy (range, 54-66 Gy). Seventeen patients (63%) received neoadjuvant or
      adjuvant chemotherapy. Fifteen (56%) received cisplatin concurrently with IMRT.
      Rates of overall survival and progression-free survival following salvage IMRT
      were determined using the Kaplan-Meier method, and differences between subgroups
      were assessed using the log-rank statistic. RESULTS: Of the 27 patients, 19 (70%)
      had local control of paraortic disease after a median follow-up time of 25 months
      (range, 4-83 months). Two-year actuarial overall survival and progression-free
      survival rates were 63% and 53%, respectively. Five patients (19%) experienced
      severe late gastrointestinal toxic effects (grade 3-5). CONCLUSIONS: IMRT can
      serve as salvage therapy of paraortic recurrence of endometrial cancer. However,
      the risk of severe gastrointestinal toxic effects is high, and care should be
      taken during treatment planning to minimize the dose to the small bowel.

PMID- 24674270
TI  - Importance of initial aggressive treatment for pineal parenchymal tumor of
      intermediate differentiation: A case report and review of literature.

PMID- 24674271
TI  - Therapeutic plasma exchange in glucocorticosteroid-unresponsive patients with
      Clinically Isolated Syndrome.
AB  - Clinically Isolated Syndromes (CIS) summarize clinical features of possible
      multiple sclerosis (MS) as a first clinical event of the disease. Escalation
      therapy in CIS episodes comprises high dose glucocorticosteroid (GCS) treatment
      followed by therapeutic plasma exchange (TPE) in patients unresponsive to GCS.
      The aim of our study was to analyze TPE effects in CIS patients. Eleven GCS
      unresponsive patients exhibiting CIS were treated with TPE. A median of 5.0
      (range 3-8) treatments were performed with a median exchange volume of 3.0 L
      (range 2.2-3.5 L). Standard diagnostic results in CIS patients were collected. In
      10 out of 11 patients clinical improvement was observed. In Expanded Disability
      Status Scale (EDSS) Scoring, a commonly used score to assess disability in MS and
      CIS patients, significant improvement was shown as well. One patient was a non
      responder to TPE. Apheresis treatments were well tolerated in all patients. In
      the medical control of GCS-unresponsive CIS episodes, TPE appears to be an
      effective and well-tolerated treatment option. TPE response in CIS patients is
      comparable to TPE results in GCS-unresponsive MS relapses. Further prospective
      studies are indicated.

PMID- 24674272
TI  - Iron and noncontrast magnetic resonance T2* as a marker of intraplaque iron in
      human atherosclerosis.
AB  - OBJECTIVE: Iron has been implicated in atherogenesis and plaque destabilization,
      whereas less is known about iron-related proteins in this disease. We compared ex
      vivo quantities with in vivo vessel wall T2*, which is a noncontrast magnetic
      resonance relaxation time that quantitatively shortens with increased tissue iron
      content. We also tested the hypothesis that patients with carotid atherosclerosis
      have abnormal T2* times vs controls that would help support a role for iron in
      human atherosclerosis. METHODS: Forty-six patients undergoing carotid
      endarterectomy and 14 subjects without carotid disease were prospectively
      enrolled to undergo carotid magnetic resonance imaging. Ex vivo measurements were
      performed on explanted plaque and 17 mammary artery samples. RESULTS: Plaques vs
      normal arteries had higher levels of ferritin (median, 7.3 [interquartile range
      (IQR), 4-13.8] vs 1.0 [IQR, 0.6-1.3] ng/mg; P < .001) and oxidized low-density
      lipoprotein (median, 0.17 [IQR, 0.12-0.30] vs 0.01 [IQR, 0.003-0.03] ng/mg; P <
      .001) as well as hepcidin (median, 8.7 [IQR, 4.6-12.4] vs 2.6 [IQR, 1.3-7.0]
      ng/mL; P = .03); serum hepcidin levels did not distinguish atherosclerosis
      patients from controls (median, 40.6 [IQR, 18.8-88.6] vs 33.9 [IQR, 17.6-55.2]; P
      = .42). Shorter in vivo T2* paralleled larger plaque volume (rho = -.44; P =
      .01), and diseased arteries had shorter T2* values compared with controls
      (median, 17.7 +/- 4.3 vs 23.0 +/- 2.4 ms; P < .001). CONCLUSIONS: Diseased
      arteries have greater levels of iron-related proteins ex vivo and shorter T2*
      times in vivo. Further studies should help define the role of T2* as a biomarker
      of iron and atherosclerosis.

PMID- 24674273
TI  - Anticonvulsant effects of N-arachidonoyl-serotonin, a dual fatty acid amide
      hydrolase enzyme and transient receptor potential vanilloid type-1 (TRPV1)
      channel blocker, on experimental seizures: the roles of cannabinoid CB1 receptors
      and TRPV1 channels.
AB  - Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH
      enzyme, has anticonvulsant effects, which are mediated by CB1 receptors.
      Anandamide, however, also activates TRPV1 channels, generally with an opposite
      outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV1
      blockade with N-arachidonoyl-serotonin (AA-5-HT) would be efficacious in
      inhibiting pentylenetetrazole (PTZ)-induced seizures in mice. We also
      investigated the contribution of CB1 activation and TRPV1 blockade to the overt
      effect of AA-5-HT. In the first experiment, injection of AA-5-HT (0.3-3.0 mg/kg)
      delayed the onset and reduced the duration of PTZ (60 mg)-induced seizures in
      mice. These effects were reversed by pre-treatment with the CB1 antagonist, AM251
      (1.0-3.0 mg/kg). Finally, we observed that administration of the selective TRPV1
      antagonist, SB366791 (0.1-1 mg/kg), did not entirely mimic AA-5-HT effects. In
      conclusion, AA-5-HT alleviates seizures in mice, an effect inhibited by CB1
      antagonism, but not completely mimicked by TRPV1 blockage, indicating that the
      overall effect of AA-5-HT seems to depend mainly on CB1 receptors. This may
      represent a new strategy for the development of drugs against seizures,
      epilepsies and related syndromes.

PMID- 24674275
TI  - The professionalism disconnect: do entering residents identify yet participate in
      unprofessional behaviors?
AB  - BACKGROUND: Professionalism has been an important tenet of medical education, yet
      defining it is a challenge. Perceptions of professional behavior may vary by
      individual, medical specialty, demographic group and institution. Understanding
      these differences should help institutions better clarify professionalism
      expectations and provide standards with which to evaluate resident behavior.
      METHODS: Duke University Hospital and Vidant Medical Center/East Carolina
      University surveyed entering PGY1 residents. Residents were queried on two
      issues: their perception of the professionalism of 46 specific behaviors related
      to training and patient care; and their own participation in those specified
      behaviors. The study reports data analyses for gender and institution based upon
      survey results in 2009 and 2010. The study received approval by the Institutional
      Review Boards of both institutions. RESULTS: 76% (375) of 495 PGY1 residents
      surveyed in 2009 and 2010 responded. A majority of responders rated all 46
      specified behaviors as unprofessional, and a majority had either observed or
      participated in each behavior. For all 46 behaviors, a greater percentage of
      women rated the behaviors as unprofessional. Men were more likely than women to
      have participated in behaviors. There were several significant differences in
      both the perceptions of specified behaviors and in self-reported observation of
      and/or involvement in those behaviors between institutions.Respondents indicated
      the most important professionalism issues relevant to medical practice include:
      respect for colleagues/patients, relationships with pharmaceutical companies,
      balancing home/work life, and admitting mistakes. They reported that
      professionalism can best be assessed by peers, patients, observation of non
      medical work and timeliness/detail of paperwork. CONCLUSION: Defining
      professionalism in measurable terms is a challenge yet critical in order for it
      to be taught and assessed. Recognition of the differences by gender and
      institution should allow for tailored teaching and assessment of professionalism
      so that it is most meaningful. A shared understanding of what constitutes
      professional behavior is an important first step.

PMID- 24674276
TI  - Intracellular calcium elevation during plateau potentials mediated by
      extrasynaptic NMDA receptor activation in rat hippocampal CA1 pyramidal neurons
      is primarily due to calcium entry through voltage-gated calcium channels.
AB  - We reported previously that plateau potentials mediated by extrasynaptic N-methyl
      d-aspartate receptors (NMDARs) can be induced either by synaptic stimulation in
      the presence of glutamate transporter antagonist or by iontophoresis of NMDA in
      rat hippocampal CA1 pyramidal neurons. To examine whether the plateau potentials
      are accompanied by an elevation of intracellular Ca2+ and to determine the source
      of Ca2+ elevation, we performed Ca2+ imaging during the plateau potential.
      Neurons were loaded with Ca2+ indicator fluo-4, and the plateau potentials were
      generated either synaptically in the presence of glutamate transporter antagonist
      or by iontophoretically applying NMDA. We have found that a transient elevation
      in intracellular Ca2+ accompanies the plateau potential. The synaptically induced
      plateau potential and the Ca2+ elevation were blocked by 5,7-dichlorokynurenic
      acid (5,7-dCK), an antagonist for the glycine-binding sites of NMDAR. A mixture
      of Cd2+ and tetrodotoxin did not block NMDA-induced plateau potentials, but
      completely abolished the accompanying Ca2+ elevation in both the presence and
      absence of Mg2+ ions in the bathing solution. The NMDA-induced plateau potential
      was blocked by further adding 5,7-dCK. Our results show that the NMDAR-mediated
      plateau potential is accompanied by elevation of intracellular Ca2+ that is
      primarily caused by the influx of Ca2+ through voltage-gated Ca2+ channels.

PMID- 24674274
TI  - What are the main environmental exposures associated with elevated IgE in Cuban
      infants? A population-based study.
AB  - OBJECTIVE: Immunoglobulin E (IgE) plays a key role in allergy disease
      pathogenesis, but little is known about the environmental factors associated with
      higher IgE levels in infants. The aim of this study was to determine the risk
      factors for elevated serum total IgE infants living in Havana. METHODS: Eight
      hundred and seventy-seven infants provided blood samples. Data on allergic
      disease symptoms and a wide range of exposures were collected. RESULTS: The
      median IgE was 35 IU/ml (interquartile range 13-96). The risk of having an IgE
      level above the median was higher for children who had been breastfed for 4
      months or more (adjusted odds ratio (OR) 1.28; 95% confidence interval (CI): 1.02
      1.61) and for children who reported cockroaches in their home (OR 1.30; 95% CI:
      1.03-1.63). The risk was lower for children whose mother was in paid employment
      (OR 0.73; 95% CI: 0.54-0.97 compared with those who did not), for children living
      in homes where gas and electricity were used for cooking (OR 0.45; 95% CI: 0.32
      0.62 compared with electricity only) and for children with domestic pets at birth
      (OR 0.83; 95% CI: 0.70-1.00). There was no association between paracetamol use
      and serum IgE levels. CONCLUSIONS: Associations between gas fuel use and maternal
      employment indicate that IgE levels in early life are lower in children who may
      be living in relative affluence. The discrepancy in the effect of early exposure
      to pets or cockroaches may reflect differences in these allergens, or be
      confounded by relative affluence. Further investigation of this cohort will
      determine how these effects translate into the expression of allergic disease in
      later life.

PMID- 24674277
TI  - An innovative data collection method for investigating unresolved pain after ED
      discharge: a pilot study.
AB  - INTRODUCTION: Research focused on improving the outcome of patients with pain is
      an important aspect of emergency care, yet little information has been published
      to quantify pain severity, patient improvement, and return to independent
      function after ED discharge. Because of the paucity of available clinical data,
      this pilot study was designed to determine the acceptability and feasibility of
      using electronic data collection procedures. Specifically, we examined the
      willingness of discharged ED patients to use portable touch-screen computers as
      an alternative to traditional "paper and pencil" or telephone data collection
      methods to report postdischarge pain. METHODS: Participants in this prospective
      pilot study all reported acute pain that was unresolved at the time of ED
      discharge. Descriptive data were self-entered on touch-screen computers at ED
      discharge and 7 days later in subjects' homes. Participants completed 4 Patient
      Reported Outcomes Measurement Information System (PROMIS Network, Silver Spring,
      MD), questionnaires and the computer acceptability scale (CAS), using the
      Assessment Center platform program (National Institute of Health, Bethesda, MD)
      for instrument administration, data storage, and information retrieval.
      Determinants of study success were willingness of the participants to use touch
      screen computers, questionnaire completion time, and completeness of the data.
      RESULTS: Participants (N = 25) used touch-screen computers to complete 18
      questions at the time of ED discharge. The mean completion time was 3.54 (+/-
      1.13) minutes. Participants averaged 5.83 (+/- 2.00) minutes to complete the
      follow-up questionnaires. Ninety-two percent of subjects reported that the touch
      screen computer was easy to use. We encountered no issues with data management
      using the Assessment Center platform. DISCUSSION: Touch-screen computers are a
      feasible and acceptable approach to collecting information about how patients
      self-manage unresolved pain after discharge from an emergency department. This
      methodology offers an alternative to traditional data collection methods. These
      data can inform researchers as they design future studies and assist emergency
      nurses who are responsible for planning quality improvement initiatives.

PMID- 24674293
TI  - The protein-protein interaction network of eyestalk, Y-organ and hepatopancreas
      in Chinese mitten crab Eriocheir sinensis.
AB  - BACKGROUND: The protein-protein interaction network (PIN) is an effective
      information tool for understanding the complex biological processes inside the
      cell and solving many biological problems such as signaling pathway
      identification and prediction of protein functions. Eriocheir sinensis is a
      highly-commercial aquaculture species with an unclear proteome background which
      hinders the construction and development of PIN for E. sinensis. However, in
      recent years, the development of next-generation deep-sequencing techniques makes
      it possible to get high throughput data of E. sinensis tanscriptome and
      subsequently obtain a systematic overview of the protein-protein interaction
      system. RESULTS: In this work we sequenced the transcriptional RNA of eyestalk, Y
      organ and hepatopancreas in E. sinensis and generated a PIN of E. sinensis which
      included 3,223 proteins and 35,787 interactions. Each protein-protein interaction
      in the network was scored according to the homology and genetic relationship. The
      signaling sub-network, representing the signal transduction pathways in E.
      sinensis, was extracted from the global network, which depicted a global view of
      the signaling systems in E. sinensis. Seven basic signal transduction pathways
      were identified in E. sinensis. By investigating the evolution paths of the seven
      pathways, we found that these pathways got mature in different evolutionary
      stages. Moreover, the functions of unclassified proteins and unigenes in the PIN
      of E. sinensis were predicted. Specifically, the functions of 549 unclassified
      proteins related to 864 unclassified unigenes were assigned, which respectively
      covered 76% and 73% of all the unclassified proteins and unigenes in the network.
      CONCLUSIONS: The PIN generated in this work is the first large-scale PIN of
      aquatic crustacean, thereby providing a paradigmatic blueprint of the aquatic
      crustacean interactome. Signaling sub-network extracted from the global PIN
      depicts the interaction of different signaling proteins and the evolutionary
      paths of the identified signal transduction pathways. Furthermore, the function
      assignment of unclassified proteins based on the PIN offers a new reference in
      protein function exploration. More importantly, the construction of the E.
      sinensis PIN provides necessary experience for the exploration of PINs in other
      aquatic crustacean species.

PMID- 24674294
TI  - Time-restricted feeding and the realignment of biological rhythms: translational
      opportunities and challenges.
AB  - It has been argued that circadian dysregulation is not only a critical inducer
      and promoter of adverse health effects, exacerbating symptom burden, but also
      hampers recovery. Therefore understanding the health-promoting roles of
      regulating (i.e., restoring) circadian rhythms, thus suppressing harmful effects
      of circadian dysregulation, would likely improve treatment. At a critical care
      setting it has been argued that studies are warranted to determine whether there
      is any use in restoring circadian rhythms in critically ill patients, what
      therapeutic goals should be targeted, and how these could be achieved.
      Particularly interesting are interventional approaches aiming at optimizing the
      time of feeding in relation to individualized day-night cycles for patients
      receiving enteral nutrition, in an attempt to re-establish circadian patterns of
      molecular expression. In this short review we wish to explore the idea of
      transiently imposing (appropriate, but yet to be determined) circadian
      rhythmicity via regulation of food intake as a means of exploring rhythm-setting
      properties of metabolic cues in the context of improving immune response. We
      highlight some of the key elements associated with his complex question
      particularly as they relate to: a) stress and rhythmic variability; and b)
      metabolic entrainment of peripheral tissues as a possible intervention strategy
      through time-restricted feeding. Finally, we discuss the challenges and
      opportunities for translating these ideas to the bedside. 

PMID- 24674295
TI  - Gestational trophoblastic neoplasia after achieving a nondetectable serum human
      chorionic gonadotrophin level.
AB  - OBJECTIVE: To determine the risk of recurrent trophoblastic disease after
      normalisation of human chorionic gonadotrophin (hCG) levels in women with
      hydatidiform mole. DESIGN: A retrospective review of data from a national
      gestational trophoblastic disease centre. SETTING: The Trophoblastic Disease
      Unit, Dakar, Senegal. SAMPLE: Women with pregnancies affected by hydatidiform
      mole registered between 2006 and 2012. METHODS: The women were followed up in
      accordance with the hospital protocol 'Score de Dakar'. For women who progressed
      to gestational trophoblastic neoplasia (GTN) the time to onset of GTN, treatment
      and evolution were evaluated. The rate of evolution to GTN after normalisation of
      hCG was determined. MAIN OUTCOME MEASURES: Rate of occurrence of GTN after
      chemotherapy for hydatidiform mole. RESULTS: Five hundred and thirty-one women
      were diagnosed to have molar pregnancies. According to the hospital's protocol,
      107 (20.2%) of these had chemotherapy and 224 (42.2%) had prophylactic
      chemotherapy. Five hundred and thirteen women (96.4%; 95% confidence interval
      [95% CI] 95.05-98.14%) achieved remission. Eighteen women (3.4%; 95% CI 1.86
      4.94%) developed GTN (11 before remission and seven after remission). Seven women
      out of the 18 developed GTN after hCG normalisation (1.3%). Five of these seven
      were diagnosed beyond the recommended period of follow up. The mean interval to
      diagnosis of GTN was 18.7 months. These seven women underwent combination
      chemotherapy: five achieved complete remission whereas two died from GTN.
      CONCLUSIONS: Cytotoxic therapy for hydatidiform mole does not prevent GTN, it
      delays its diagnosis and promotes GTN after normalisation of hCG.

PMID- 24674296
TI  - Do negative stimulant-related attitudes vary for prescription stimulants and
      cocaine among college students?
AB  - Nonmedical prescription stimulant use (NPS) has become an increasing problem for
      college students across the United States. Many engage in NPS due to the belief
      that their academic functioning will improve - a belief that rarely extends to
      other illicit stimulants. Because positive attitudes toward substances
      potentially predict the maintenance of current and future use, the aim of the
      current study was to directly compare attitudes toward different stimulants of
      abuse (prescription stimulants and cocaine) to ascertain whether attitudes were
      generally more positive as a function of both drug and drug user type. Ninety-one
      participants completed a brief attitudinal index assessing attitudes for both
      prescription stimulants and cocaine. Participants held stronger positive
      attitudes toward prescription stimulants than cocaine on a variety of items. NPS
      users reported more positive attitudes toward prescription stimulants than both
      nonusers and cocaine users. Nonusers reported more negative cocaine-related
      attitudes than cocaine users and polydrug users (users of both prescription
      stimulants and cocaine). Intervention programs may benefit from highlighting the
      negative consequences of NPS, particularly by way of comparisons to cocaine.
      Doing so may heighten awareness on the overlap of adverse outcomes resulting from
      use between these stimulants.

PMID- 24674297
TI  - Is additional hyperbaric oxygen therapy cost-effective for treating ischemic
      diabetic ulcers? Study protocol for the Dutch DAMOCLES multicenter randomized
      clinical trial?
AB  - BACKGROUND: The value of hyperbaric oxygen therapy (HBOT) in the treatment of
      diabetic ulcers is still under debate. Available evidence suggests that HBOT may
      improve the healing of diabetic ulcers, but it comes from small trials with
      heterogeneous populations and interventions. The DAMOCLES-trial will assess the
      (cost-)effectiveness of HBOT for ischemic diabetic ulcers in addition to standard
      of care. METHODS: In a multicenter randomized clinical trial, including 30
      hospitals and all 10 HBOT centers in the Netherlands, we plan to enroll 275
      patients with Types 1 or 2 diabetes, a Wagner 2, 3 or 4 ulcer of the leg present
      for at least 4 weeks, and concomitant leg ischemia, defined as an ankle systolic
      blood pressure of <70 mmHg, a toe systolic blood pressure of <50 mmHg or a
      forefoot transcutaneous oxygen tension (TcpO2) of <40 mmHg. Eligible patients may
      be candidates for revascularization. Patients will be randomly assigned to
      standard care with or without 40 HBOT-sessions. RESULTS: Primary outcome measures
      are freedom from major amputation after 12 months and achievement of, and time
      to, complete wound healing. Secondary endpoints include freedom from minor
      amputations, ulcer recurrence, TcpO2 , quality of life, and safety. In addition,
      we will assess the cost-effectiveness of HBOT for this indication. CONCLUSION:
      The DAMOCLES trial will be the largest trial ever performed in the realm of HBOT
      for chronic ulcers, and it is unique for addressing patients with ischemic
      diabetic foot ulcers who may also receive vascular reconstructions. This matches
      the treatment dilemma in current clinical practice.

PMID- 24674298
TI  - Gender-specific outcomes of bladder cancer patients: a stage-specific analysis in
      a contemporary, homogenous radical cystectomy cohort.
AB  - INTRODUCTION: Controversial findings regarding gender-specific oncological
      outcomes of urothelial carcinoma of the bladder (UCB) have recently been
      reported. The aim of this study was to analyze gender-specific outcomes using a
      stage-adjusted approach in a homogenous, contemporary radical cystectomy (RC)
      cohort. MATERIAL AND METHODS: We prospectively collected data of 517 UCB patients
      treated with RC and pelvic lymphadenectomy without neoadjuvant chemotherapy at
      our institution between 1996 and 2010. Stage-adjusted uni- and multivariable Cox
      regression models analyzed the association of gender with disease recurrence,
      cancer-specific mortality and overall survival. RESULTS: In total, 398 (77%)
      patients were male and 119 (23%) were female. Compared to men, women were more
      likely to have advanced tumor stages (p = 0.017), nodal metastasis (p = 0.047)
      and received more frequently adjuvant chemotherapy (p = 0.009). At a median
      follow-up of 44 months, there was no statistical difference in disease
      recurrence, cancer-specific mortality and overall survival between both genders
      when analyzed as a group. In stage-adjusted analyses, only women with non
      invasive UCB were more likely to die of UCB compared to the male counterparts (p
      = 0.013). In gender-specific multivariable analyses that adjusted for standard
      clinico-pathologic features, pathologic tumor stage was an independent predictor
      for disease recurrence (p-values <=0.047) and cancer-specific mortality (p-values
      <=0.049), respectively. CONCLUSION: Women present with more aggressive tumor
      biologic features at RC, however this did not translate into inferior outcomes
      compared to men in stage-specific analyses in our cohort. Tumor stage is the most
      important factor influencing the course of disease in both genders. Validation of
      our findings is warranted in a larger cohort.

PMID- 24674299
TI  - [An ophthalmologic diagnostic error leading to a rare systemic diagnosis: Erdheim
      Chester disease].
AB  - INTRODUCTION: Erdheim-Chester disease is a rare systemic disease. The diagnosis
      is difficult due to significant clinical and morphological polymorphism. Orbital
      involvement is rare, but constitutes a classic means of detection. OBSERVATION:
      We report the case of a 60-year-old man, who consulted for evaluation of
      bilateral retro-orbital tumors. These tumors had been discovered on head CT two
      years previously during work-up of proptosis. Two biopsies were performed. The
      first one revealed polymorphous inflammatory tissue. The second one revealed
      intense granulomatous reaction, rich in non-specific foamy histiocytes. Thoracic
      abdominal-pelvic CT scan detected peri-aortic and retroperitoneal infiltration.
      The association of these signs pointed to a diagnosis of Erdheim-Chester disease,
      confirmed by the re-examination of the histological samples. DISCUSSION: Erdheim
      Chester disease is a rare non-Langerhans histiocytosis with a specific tropism
      for perivascular and fatty connective tissue. The cause is not known. The
      diagnosis of this systemic disease is histological. CONCLUSION: In the case of
      bilateral intra-orbital tumors, the diagnosis of Erdheim-Chester disease must be
      considered.

PMID- 24674300
TI  - Four-dimensional computed tomography for parathyroid localization: a new imaging
      modality.
AB  - INTRODUCTION: Four-dimensional computed tomography (4DCT) is a new parathyroid
      localization technique not previously reported in Australia. It provides both
      functional and anatomical imaging in a single test, with superior sensitivity
      compared with sestamibi scintigraphy (SeS). This study examines the utility of
      4DCT in defined clinical situations. METHODS: This is a retrospective cohort
      study in a tertiary referral hospital setting. One hundred consecutive operative
      cases of primary hyperparathyroidism (99 patients) undergoing both preoperative
      4DCT and SeS. Localization studies were correlated with operative findings,
      histopathology and clinical outcomes. The utility of 4DCT was analysed in three
      common clinical settings: primary cases with positive SeS (Group A, n = 68),
      primary cases with negative SeS (Group B, n = 21) and re-operative cases (Group
      C, n = 11). RESULTS: The overall sensitivity of 4DCT was 92% compared with 70%
      for SeS. The sensitivity of 4DCT was superior to SeS in Groups B and C (76%
      versus 0% and 91% versus 46%, respectively). The overall cure rate was 98%, with
      94% of cases completed as minimally invasive procedures. Up to 62% of Group B
      cases potentially avoided a bilateral neck exploration owing to a positive 4DCT.
      CONCLUSIONS: 4DCT is an accurate technique providing both functional and
      anatomical localization of abnormal parathyroid glands. However, the advantage of
      speed and simplicity in image acquisition needs to be balanced against the small
      risk of increased radiation exposure in the younger patient group.

PMID- 24674302
TI  - Retrospective chart review of obesity and episodic and chronic illness among
      rural Mexican-American adolescents accessing rural health clinic services.
AB  - Obesity impacts the physical and psychological health of children and
      adolescents, and is a risk factor for development of episodic and chronic
      illness. Rural Mexican-American adolescents are at risk for obesity and
      associated chronic illnesses.The study used a retrospective chart review of data
      collected routinely in a rural health clinic setting from 1 January 2005 to 31
      December 2010 to assess incidence of overweight/obesity status and episodic or
      chronic illness among Mexican-American adolescents aged 12-18 years. Analyses
      included body mass index, age, gender, and episodic or chronic illness diagnoses.
      Two hundred twelve charts were audited; women (n = 114, 53.8%), men (n = 98
      46.2%); normal (n = 105, 49.5%), overweight/obese (n = 107, 50.5%). There were
      more female normal (n = 61, 53.5%) vs. overweight/obese (n = 53, 46.5%). More
      male overweight/obese (n = 54, 55.1%) than normal weight (n = 44, 44.9%). Age at
      first documented overweight/obesity status occurred in early adolescence (median
      = 13 years, mode = 12 years). Chronic illness incidence was higher among men than
      women, and overweight/obese vs. normal weight adolescents and in sub
      categorizations by weight and specific illness. Incidence of episodic illness was
      higher among women than men, with variation by weight and specific illness.
      Disproportionately high incidence of episodic or chronic illness and
      overweight/obesity identified among rural Mexican-American adolescents compels
      intervention modification to improve effectiveness. 

PMID- 24674301
TI  - Plasmodium falciparum antigenic variation: relationships between widespread
      endothelial activation, parasite PfEMP1 expression and severe malaria.
AB  - BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) is a
      family of variant surface antigens (VSA) that mediate the adhesion of parasite
      infected erythrocytes to capillary endothelial cells within host tissues. Opinion
      is divided over the role of PfEMP1 in the widespread endothelial activation
      associated with severe malaria. In a previous study we found evidence for
      differential associations between defined VSA subsets and specific syndromes of
      severe malaria: group A-like PfEMP1 expression and the "rosetting" phenotype were
      associated with impaired consciousness and respiratory distress, respectively.
      This study explores the involvement of widespread endothelial activation in these
      associations. METHODS: We used plasma angiopoietin-2 as a marker of widespread
      endothelial activation. Using logistic regression analysis, we explored the
      relationships between plasma angiopoietin-2 levels, parasite VSA expression and
      the two syndromes of severe malaria, impaired consciousness and respiratory
      distress. RESULTS: Plasma angiopoietin-2 was associated with both syndromes. The
      rosetting phenotype did not show an independent association with respiratory
      distress when adjusted for angiopoietin-2, consistent with a single pathogenic
      mechanism involving widespread endothelial activation. In contrast, group A-like
      PfEMP1 expression and angiopoietin-2 maintained independent associations with
      impaired consciousness when adjusted for each other. CONCLUSION: The results are
      consistent with multiple pathogenic mechanisms leading to severe malaria and
      heterogeneity in the pathophysiology of impaired consciousness. The observed
      association between group A-like PfEMP1 and impaired consciousness does not
      appear to involve widespread endothelial activation.

PMID- 24674304
TI  - beta-Catenin regulates membrane potential in muscle cells by regulating the
      alpha2 subunit of Na,K-ATPase.
AB  - Muscle beta-catenin has been shown to play a role in the formation of the
      neuromuscular junction (NMJ). Our previous studies showed that muscle-specific
      conditional knockout of beta-catenin (HSA-beta-cat(-/-) ) results in early
      postnatal death in mice. To understand the underlying mechanisms, we investigated
      the electrophysiological properties of muscle cells from HSA-beta-cat(-/-) and
      control mice, and found that, in the absence of muscle beta-catenin, the resting
      membrane potential (RMP) depolarised in muscle cells from the diaphragm,
      gastrocnemius and extensor digitorum longus muscles. Furthermore, in a primary
      line of mouse myoblasts (C2C12 cells) transfected with small-interfering RNAs
      targeting beta-catenin, the RMP was depolarised as well. Finally, the expression
      levels of the alpha2 subunit of sodium/potassium adenosine triphosphatase were
      reduced by beta-catenin knockdown in vitro or deletion in vivo. These results
      suggest a possible mechanism underlying the depolarised RMP in the absence of
      muscle beta-catenin, and provide additional evidence supporting a role for beta
      catenin in the development of NMJs. 

PMID- 24674305
TI  - Effect on anal pressure of percutaneous posterior tibial nerve stimulation for
      faecal incontinence.
AB  - AIM: Previous studies on percutaneous posterior tibial nerve stimulation (PTNS)
      for faecal incontinence do not report anal pressure changes. In the present study
      the effect of percutaneous PTNS on anal manometry was determined. METHOD: This
      was a prospective observational study of patients with faecal incontinence. They
      underwent one 30-min session of PTNS weekly for 12 consecutive weeks. Patients
      who showed improvement were given six more sessions at 2-weekly intervals. Anal
      manometry was performed before and after treatment. Clinical data including the
      Wexner score, psychological testing, quality of life using the Fecal Incontinence
      Quality of Life Score and the contents of a continence diary were recorded before
      and after the procedure. RESULTS: Twenty-four patients were included in the study
      of whom 17 (70.83%) demonstrated some degree of clinical or manometric
      improvement at 3 months. Before treatment 18 patients had urgency of <1 min. At 3
      and 6 months this had risen to 5 min in 62.5% and 70.83% (P < 0.001). The anal
      resting pressure increased from 21.7 to 37.6 mmHg (P = 0.021), the maximum
      squeeze pressure from 58.2 to 72.2 mmHg (P = 0.045) and the Wexner score fell
      from 15 to 10 (P = 0.018) at 6 months. Predictive factors for a response included
      fewer than three incontinent episodes per week (P = 0.027). Negative predictive
      factors included episiotomy and an initial Wexner score of > 12 (P = 0.035).
      CONCLUSION: Percutaneous PTNS was effective in over 70% of patients in the
      present study with improvements in urgency, anal pressures and Wexner score.

PMID- 24674306
TI  - Studies of the safety, pharmacokinetics and immunogenicity of repeated doses of
      intravenous staphylococcal protein A in cynomolgus monkeys.
AB  - Three Good Laboratory Practice safety studies were performed with intravenous
      injections of highly purified staphylococcal protein A (SPA) in cynomolgus
      monkeys, in support of a clinical development programme utilizing this protein as
      an immunomodulator. These studies established a no-observable-adverse-effect
      level (NOAEL) for up to 12 weekly doses of SPA, as well as toxicokinetic profiles
      for SPA, evaluation of antiproduct antibodies and biomarkers to better
      characterize the pharmacodynamic response to SPA. Biomarkers included neopterin,
      C-reactive protein (CRP), troponin I and the change in the blood absolute
      lymphocyte count (ALC) 24 hr after SPA dosing. The transient decrease in ALC
      noted at 24 hr after dosing was similar to that seen in human Phase 1 trials. The
      majority of active-treated monkeys developed antibodies against SPA. Cmax was not
      affected by development of antidrug antibodies (ADAs), and after the first dose
      was 87 (SD 19) ng/mL, 330 (SD 84) ng/mL and 1191 (SD 208) ng/mL for 5, 25 and 100
      MUg/kg doses, respectively. The development of ADAs increased plasma clearance of
      SPA. By the sixth weekly dose, the AUC was decreased by 76%, 54% and 66% for the
      5, 25 and 100 MUg/kg dose groups, respectively. These results indicate that SPA
      can be administered intravenously to non-human primates without observable
      toxicity at weekly doses of up to 100 MUg/kg. 

PMID- 24674308
TI  - Editor's Note: The importance of understanding patient safety, international
      scope, and scientific misconduct.

PMID- 24674307
TI  - A prospective analysis of false positive events in a National Colon Cancer
      Surveillance Program.
AB  - BACKGROUND: The survival benefits of colon cancer surveillance programs are well
      delineated, but less is known about the magnitude of false positive testing. The
      objective of this study was to estimate the false positive rate and positive
      predictive value of testing as part of a surveillance program based on national
      guidelines, and to estimate the degree of testing and resource use needed to
      identify a curable recurrence. METHODS: Analysis of clinically significant events
      leading to suspicion of cancer recurrence, false positive events, true cancer
      recurrences, time to confirmation of diagnosis, and resource use (radiology,
      blood samples, colonoscopies, consultations) among patients included in a
      randomised colon cancer surveillance trial. RESULTS: 110 patients surgically
      treated for colon cancer were followed according to national guidelines for 1884
      surveillance months. 1105 tests (503 blood samples, 278 chest x-rays, 209 liver
      ultrasounds, 115 colonoscopies) and 1186 health care consultations were
      performed. Of the 48 events leading to suspicion of cancer recurrence, 34 (71%)
      represented false positives. Thirty-one (65%) were initiated by new symptoms, and
      17 (35%) were initiated by test results. Fourteen patients had true cancer
      recurrence; 7 resections of recurrent disease were performed, 4 of which were
      successful R0 metastasis Resections. 276 tests and 296 healthcare consultations
      were needed per R0 resection; the cost per R0 surgery was L 103207. There was a
      29% probability (positive predictive value) of recurrent cancer when a diagnostic
      work-up was initiated based on surveillance testing or patient complaints.
      CONCLUSION: We observed a high false positive rate and low positive predictive
      value for significant clinical events suggestive of possible colorectal cancer
      relapse in the setting of a post-treatment surveillance program based on national
      guidelines. Providers and their patients should have an appreciation for the
      modest positive predictive value inherent in colorectal cancer surveillance
      programs in order to make informed choices, which maximize quality of life during
      survivorship. Better means of tailoring surveillance programs based on patient
      risk would likely lead to more effective and cost-effective post-treatment follow
      up. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00572143. Date of trial
      registration: 11th of December 2007.

PMID- 24674309
TI  - Catching errors with patient-specific pretreatment machine log file analysis.
AB  - PURPOSE: A robust, efficient, and reliable quality assurance (QA) process is
      highly desired for modern external beam radiation therapy treatments. Here, we
      report the results of a semiautomatic, pretreatment, patient-specific QA process
      based on dynamic machine log file analysis clinically implemented for intensity
      modulated radiation therapy (IMRT) treatments delivered by high energy linear
      accelerators (Varian 2100/2300 EX, Trilogy, iX-D, Varian Medical Systems Inc,
      Palo Alto, CA). The multileaf collimator machine (MLC) log files are called
      Dynalog by Varian. METHODS AND MATERIALS: Using an in-house developed computer
      program called "Dynalog QA," we automatically compare the beam delivery
      parameters in the log files that are generated during pretreatment point dose
      verification measurements, with the treatment plan to determine any discrepancies
      in IMRT deliveries. Fluence maps are constructed and compared between the
      delivered and planned beams. RESULTS: Since clinical introduction in June 2009,
      912 machine log file analyses QA were performed by the end of 2010. Among these,
      14 errors causing dosimetric deviation were detected and required further
      investigation and intervention. These errors were the result of human operating
      mistakes, flawed treatment planning, and data modification during plan file
      transfer. Minor errors were also reported in 174 other log file analyses, some of
      which stemmed from false positives and unreliable results; the origins of these
      are discussed herein. CONCLUSIONS: It has been demonstrated that the machine log
      file analysis is a robust, efficient, and reliable QA process capable of
      detecting errors originating from human mistakes, flawed planning, and data
      transfer problems. The possibility of detecting these errors is low using point
      and planar dosimetric measurements.

PMID- 24674310
TI  - Comment on "Catching errors with patient-specific pretreatment machine log file
      analysis".

PMID- 24674311
TI  - Radiation dose and contralateral breast cancer risk associated with megavoltage
      cone-beam computed tomographic image verification in breast radiation therapy.
AB  - PURPOSE: To measure and compare organ doses from a standard tangential breast
      radiation therapy treatment (50 Gy delivered in 25 fractions) and a megavoltage
      cone-beam computed tomography (MV-CBCT), taken for weekly image verification, and
      assess the risk of radiation-induced contralateral breast cancer. METHODS AND
      MATERIALS: Organ doses were measured with thermoluminescent dosimeters placed
      strategically within a female anthropomorphic phantom. The risk of radiation
      induced secondary cancer of the contralateral breast was estimated from these
      values using excess absolute risk and excess relative risk models. RESULTS: The
      effective dose from a MV-CBCT (8-monitor units) was 35.9 +/- 0.2 mSv. Weekly MV
      CBCT imaging verification contributes 0.5% and 17% to the total ipsilateral and
      contralateral breast dose, respectively. For a woman irradiated at age 50 years,
      the 10-year postirradiation excess relative risk was estimated to be 0.8 and 0.9
      for treatment alone and treatment plus weekly MV-CBCT imaging, respectively. The
      10-year postirradiation excess absolute risk was estimated to be 4.7 and 5.6 per
      10,000 women-years. CONCLUSIONS: The increased dose and consequent radiation
      induced second cancer risk as calculated by this study introduced by the imaging
      verification protocols utilizing MV-CBCT in breast radiation therapy must be
      weighed against the benefits of more accurate treatment. As additional image
      verification becomes more common, it is important that data be collected in
      regard to long-term malignancy risk.

PMID- 24674312
TI  - Systematic review of brain metastases prognostic indices.
AB  - PURPOSE: A variety of prognostic indices for patients with brain metastases have
      been published in the literature, to guide clinical decision-making and clinical
      trial stratification. The purpose of this investigation is to perform a
      systematic review of all primary and validation reports of such prognostic
      systems. An assessment of index operating characteristics and misclassification
      rates was performed to assist in highlighting the advantages and disadvantages of
      competing systems. METHODS AND MATERIALS: A systematic review of the English
      language literature regarding primary and validation brain metastases prognostic
      indices was performed according to PRISMA guidelines. Clinical, treatment,
      statistical, and prognostic index classification details were abstracted and
      organized into tables. Receiver operator characteristic curves were created from
      available Kaplan-Meier curves using a novel digitization procedure. From these
      curves, various operating characteristics such as positive predictive value
      (PPV), negative predictive value (NPV), accuracy (ACC), likelihood ratio (LR),
      and area under the curve (AUC) were calculated. Additionally, the major
      misclassification rate (MMR), defined as good or poor risk patients misclassified
      into the opposite group, was calculated for all available receiver operator
      characteristic curves. RESULTS: A total of 9 prognostic systems have been
      published in the medical literature. In terms of the poor prognostic group,
      observed ranges are as follow: for PPV (0.25-0.72), NPV (0.72-0.97), ACC (0.57
      0.95), LR (1.54-16.4), AUC (0.64-0.90), and MMR (0.02-0.39). Similarly, ranges of
      PPV (0.52-0.96), NPV (0.31-0.77), ACC (0.41-0.74), LR (1.69-20), AUC (0.64-0.89),
      and MMR (0.00-0.19) were observed for the good prognostic group. CONCLUSIONS:
      Operating characteristic and major misclassification analyses of all available
      prognostic index information demonstrated a range of results. As the ideal
      prognostic index has not yet been defined, further research into alternative
      approaches is warranted. Information contained within this report can serve as a
      benchmark for future investigations of existing and proposed prognostic indices.

PMID- 24674313
TI  - Methods for image guided and intensity modulated radiation therapy in high-risk
      abdominal neuroblastoma.
AB  - PURPOSE: Our purpose was to determine methods for image guided intensity
      modulated radiation therapy (IMRT) in pediatric abdominal high-risk neuroblastoma
      and to quantify the degree of normal tissue dose reduction by using volumes
      compliant with International Commission on Radiation Units and Measurements
      (ICRU) Report 62. METHODS AND MATERIALS: Eight consecutive children with high
      risk abdominal neuroblastoma (median age, 2.5 years; range, 20 months-5 years)
      were treated with IMRT using volumes accounting for physiologic motion
      (IMRT_phys) and daily pretreatment cone beam computed tomographic localization.
      Comparative IMRT planning using conventional volumes (IMRT_std) provided
      quantification for dose reduction to normal tissues. RESULTS: The IMRT_phys plan
      reduced the mean planning target volume from 668.8 +/- 200.6 cc to 393.0 +/-
      132.5 cc (P < .001) and reduced mean body V50 from 1774.4 +/- 383.9 cc to 1385.7
      +/- 365.7 cc (P < .001). The IMRT_phys plan reduced the percent mean dose to the
      ipsilateral kidney from 70.1% +/- 4.3% to 66.0% +/- 5.2% (P =.002); that to the
      contralateral kidney was reduced from 56.3% +/- 7.0% to 40.7% +/- 9.5% (P <
      .001), and that to the liver was reduced from 57.8% +/- 16.0% to 22.1% +/- 6.8%
      (P = .001). CONCLUSIONS: For IMRT planning, ICRU 62-compliant volume definition
      with image guidance in the pediatric abdomen enables volumetric reduction of the
      planning target volume and reduces normal tissue dose. These methods provide a
      framework for more conformal treatment planning in the pediatric abdomen.

PMID- 24674314
TI  - Pilot study of a computed tomography-compatible shielded intracavitary
      brachytherapy applicator for treatment of cervical cancer.
AB  - PURPOSE: The traditional Fletcher-Williamson tandem and ovoid brachytherapy
      applicators for treatment of cervical cancer have ovoid shields that reduce the
      dose to the bladder and rectum. However, these shields produce artifact on
      computed tomography (CT) that prevents acquisition of high-quality images. To
      address this limitation, we designed and tested a novel CT-compatible applicator
      with movable shields, called MDA(3). METHODS AND MATERIALS: Fifteen patients with
      stage IB1-IIB cervical cancer requiring definitive radiation therapy were
      enrolled in a prospective pilot study to evaluate image quality with the MDA(3).
      Image quality was assessed by comparing an initial scan obtained with the shields
      shifted to minimize shield artifact to a second scan obtained with the shields in
      treatment position. The 2 scans were then compared by a radiation oncologist
      blinded to the image source. In addition, image quality was assessed by analysis
      of Hounsfield values in the normal tissues. RESULTS: The MDA(3) was successfully
      employed for intracavitary brachytherapy in 15 patients. CT images obtained with
      the shields shifted were superior to CT images obtained with the shields in
      treatment position in every case as evaluated by the radiation oncologist (P <
      .0001). The presence of the shields in the treatment position significantly
      increased the mean Hounsfield values within the bladder (P = .002) and rectum (P
      = .001) due to high-density image artifact. CONCLUSIONS: This novel applicator
      provides a clinically feasible solution to overcome the limitation of lack of
      ovoid shields on currently available CT-compatible applicators.

PMID- 24674315
TI  - Four-dimensional versus 3-dimensional computed tomographic planning for gastric
      mucosa associated lymphoid tissue lymphoma.
AB  - PURPOSE: This study compares dosimetric parameters of 4-dimensional (4D) and 3
      dimensional (3D) computed tomographic (CT) planning for gastric mucosa-associated
      lymphoid tissue (MALT) lymphoma in an attempt to identify any potential benefit
      of 4DCT planning. METHODS AND MATERIALS: We identified 18 patients who received
      definitive 4DCT radiation planning from September 2006 to September 2011 for
      gastric MALT lymphoma at our institution. In addition to the kidneys and liver,
      we contoured an internal target volume (ITV) and static clinical target volume
      (sCTV) for each patient based on the 4D and 3D images, respectively, to develop
      3D conformal radiation plans. Using the static and motion plans, we measured the
      volume of ITV covered by at least 95% of the prescribed dose (V95), the minimum
      dose received by 95% of the ITV (D95), and the volume of organs receiving at
      least 20 Gy or 30 Gy (V20 or V30). RESULTS: Volumes of the ITV, motion liver,
      left kidney, and right kidney were significantly larger than their static
      counterparts. The static plan significantly lowered the ITV V95 and D95 compared
      with the motion plan. However, this undercoverage was significantly associated
      with the superior-inferior (SI) respiratory excursions. A V95 of >98% was
      observed in 92% of patients with SI excursions <15 mm versus 33% of patients with
      SI excursions >15 mm (P = .02). When compared with the motion plan, the static
      plan also significantly lowered the liver V30 and left kidney V20. CONCLUSIONS:
      The 3DCT planning can result in undercoverage of the ITV and altered estimation
      of doses to normal structures. However, in patients with limited respiratory
      excursions (<15 mm), 4D and 3D images generated similar ITV coverage.

PMID- 24674316
TI  - Low toxicity for lung tumors near the mediastinum treated with stereotactic body
      radiation therapy.
AB  - PURPOSE: To report the local control, survival, and low toxicity observed at the
      Cooper University Hospital CyberKnife Center post stereotactic body radiation
      therapy (SBRT) in the treatment of lung tumors near the mediastinum. METHODS AND
      MATERIALS: Twenty-four medically inoperable lung cancer patients with tumors near
      the mediastinum were treated using the Accuray CyberKnife system (Accuray,
      Sunnyvale, CA) with Monte Carlo dose calculations and heterogeneity corrections
      from July 2008 to May 2010. The prescription dose ranged from 28.5 Gy to 60 Gy in
      3-5 fractions. For conventional fractionation schemes, Emami et al(1) organized
      the dose tolerance limits into a unified format for clinical utility and
      partitioned them into 2 risk levels (5% and 50%) with preset volumes for most
      critical structures throughout the body. In contrast, statistical SBRT dose
      tolerance limits for mediastinal structures have not been established yet. We
      have sufficient experience at least to begin organizing a unified format with low
      risk and high-risk partitions and preset volumes for 1-5 fractions exposing
      mediastinal structures. With the help of the (dose-volume histogram) DVH
      Evaluator, a software tool developed by our senior author, each treatment plan
      was assessed for safety and feasibility prior to treatment. The DVH Evaluator was
      also used to analyze the follow-up data and to create graphs of risk, called DVH
      Risk Maps, superimposing clinical data onto the unified SBRT dose tolerance
      limits. RESULTS: It was not feasible to prescribe the doses of peripheral lung
      lesions for all tumors near the mediastinum because of known toxicity. The crude
      local tumor control rate achieved in our series was 92%. Median survival was 26.8
      months for the primary lung cases and 9.6 months for the metastatic cases. No
      patients experienced grade 3 or higher toxicities. CONCLUSIONS: We affirm that
      SBRT is feasible in the treatment of centrally located lung cancers when the dose
      tolerance limits of critical structures are diligently respected. The low adverse
      event rates that we have experienced, combined with a good local tumor control
      rate, are encouraging.

PMID- 24674317
TI  - Intensity modulated radiation therapy after radical prostatectomy: Early results
      show no decline in urinary continence, gastrointestinal, or sexual quality of
      life.
AB  - PURPOSE: Although postprostatectomy radiation therapy (PPRT) has been shown to
      improve cause-specific survival in select high-risk men, its use may be tempered
      by the concern for toxicity. Limited data exist regarding the nature of how it
      may adversely affect quality of life in the era of intensity modulated radiation
      therapy (IMRT). METHODS AND MATERIALS: Between 2007 and 2010, 78 consecutive men
      received PPRT. Salvage RT was administered to 61 (78%) men and adjuvant RT to 17
      (22%). The median dose of IMRT was 66.6 Gy (range, 60-72). Quality of life (QOL)
      data were prospectively collected using the Expanded Prostate Cancer Index
      Composite-26 tool and International Prostate Symptom Score (IPSS) at 2-, 6-, 12-,
      18-, and 24-month follow-up visits. Paired t tests and multivariate longitudinal
      analysis were used to assess the QOL measures at baseline and follow-up. RESULTS:
      No significant changes were observed for any individual QOL domain or IPSS score
      from baseline through 2-year follow-up. Global urinary irritation or obstruction
      scores were unchanged to improved over time (82, 81, 89, and 88 at baseline, 2,
      12, and 24 months, respectively; baseline to 24 months P = .06). Global urinary
      continence improved from baseline to 24 months in the subset of patients
      receiving adjuvant RT, who had higher rates of baseline urinary incontinence more
      than once daily (64% vs 28%, P = .03) and any pad use (73% vs 32%, P = .01)
      compared with the salvage subset. Global bowel domain scores were lower at 2
      months but improved with time. Sexual domain scores were also reduced at 2 months
      but otherwise unaffected over follow-up. CONCLUSIONS: Compared with baseline,
      PPRT does not appear to be associated with a significant decline in patient
      reported urinary, bowel, or sexual QOL indices 2 years after completion.

PMID- 24674318
TI  - Not all second cancers are secondary. In regard to Mourad et al: "Radiation
      induced sarcoma following radiation prophylaxis of heterotopic ossification".

PMID- 24674319
TI  - American Society for Radiation Oncology's Performance Assessment for the
      Advancement of Radiation Oncology Treatment: A practical approach for informing
      practice improvement.
AB  - PURPOSE: Performance Assessment for the Advancement of Radiation Oncology
      Treatment (PAAROT) is a practice quality improvement program. This study seeks to
      determine baseline performance rates and practice variation from PAAROT data.
      METHODS AND MATERIALS: The cohort includes all physicians from academic,
      hospital, and free-standing settings who completed at least 10 consecutive self
      audited medical records in the PAAROT program (version 2.5) from 2010 to 2011 (n
      = 519 medical records). Mean performance rates were analyzed at the physician and
      medical record levels and, where appropriate, were stratified by the physician's
      practice setting. RESULTS: Forty-nine physicians were included in the study; 22
      (45%), 17 (35%), and 10 (20%) physicians practiced in a hospital, academic, or a
      free-standing setting, respectively. The measures with a high adoption rate (more
      than 80%) include the following: documentation of history and physical; review of
      physics and dosimetry plan by radiation oncologist; patient informed risks of
      therapy; evaluation of acute symptoms during therapy; pathology in consultation
      note; communication of treatment summary within 30 days of treatment completion;
      documentation of intent of treatment, use of clinical guidelines or published
      data; and documentation of American Joint Committee on Cancer staging. Lower
      rates of adoption were noted (mean, 65%; range, 0-100%) when these measures were
      converted to a composite measure. Low adherence was noted for screening of a pain
      using a standard scale (mean, 58%; range, 0-100%). Physicians from an academic
      setting scored higher on the composite measure (40%) compared with those from a
      hospital setting (36%) and from a free-standing setting (24%); (P < .001).
      Physicians from a hospital setting scored higher on the quality indicator of
      screening for pain (54%) compared with physicians from an academic setting (35%)
      and free-standing setting (11%) (P < .001). CONCLUSIONS: This first assessment of
      PAAROT (version 2.5) data provides an initial snapshot on the use of quality
      indicators and practice patterns for radiation oncology. Self-reported practice
      data and the use of quality indicators will become important for the purpose of
      continuous, prospective evidence-based learning on an individual basis. Despite
      the small sample size, the data from this study will help address potential
      improvement opportunities for the next iteration of the PAAROT program.

PMID- 24674320
TI  - Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh
      as an alternative to tissue equivalent bolus.
AB  - PURPOSE: The use of brass mesh as a bolus is relatively uncommon in
      postmastectomy chest wall radiation therapy (PMRT). This study aimed to
      characterize the skin dose effects of using 2-mm fine brass mesh as an
      alternative to the traditional tissue-equivalent bolus during chest wall PMRT.
      METHODS AND MATERIALS: Data were collected from patients who received PMRT using
      brass mesh at the University of California Davis Department of Radiation Oncology
      between January 2008 and June 2011. Several patient characteristics including
      age, body habitus, and ethnicity were analyzed along with several disease and
      treatment characteristics to determine whether or not they had an impact on the
      skin reaction observed during radiation treatment. Additionally, in vivo surface
      dose measurements were obtained for 16 of the 48 patients (33%). RESULTS: Forty
      eight female patients aged 28-83 received PMRT using brass mesh. As expected, the
      severity of skin toxicity increased with subsequent doses of radiation with all
      patients beginning treatment with no skin reaction (National Cancer Institute
      scores [NCIS] = 0) and the majority of patients completing treatment with either
      faint to moderate erythema (n = 19, 40%, NCIS = 1) or moderate to brisk erythema
      (n = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses
      between 81% and 122% of the prescribed dose, with an average of 99% of the
      prescribed radiation dose and standard deviation of 10% being delivered.
      CONCLUSIONS: For postmastectomy chest wall radiation therapy, brass mesh is an
      effective alternative to tissue-equivalent bolus. The brass mesh achieved
      moderate erythema in the majority of patients at the end of treatment and the
      surface dose was validated using in vivo dosimetry.

PMID- 24674321
TI  - Analysis of coronary artery dosimetry in the 3-dimensional era: Implications for
      organ-at-risk segmentation and dose tolerances in left-sided tangential breast
      radiation.
AB  - PURPOSE: To evaluate the dose to the left anterior descending artery in patients
      receiving left-sided tangential breast radiation. METHODS AND MATERIALS: The
      study cohort consisted of 50 left-sided breast cancer patients who were
      sequentially simulated at our institution. The heart and left anterior descending
      (LAD) artery were contoured from its origin on the left main coronary artery down
      to the last visible segment of the vessel. Detailed dosimetry of the heart and
      LAD artery were obtained and analyzed. RESULTS: Excellent correlation between the
      dose to the heart and LAD artery was discovered. The mean LAD dose was 17.98 Gy.
      The mean dose to the proximal LAD was 2.46 Gy. The median V25 was 2.91% and the
      mean heart dose 3.10 Gy. For every 100 cGy increase in mean heart dose, mean LAD
      dose increased by 4.82 Gy. For every percent increase in the heart V10 and V25,
      there was a 2.23 Gy and 2.77 Gy increase in mean LAD dose, respectively. For
      every percent increase of heart V25, a 5.6% increase in the LAD V20 was
      demonstrated. CONCLUSIONS: The LAD artery dose correlates very closely with all
      of the commonly measured heart dose constraints, and does not need to be
      contoured separately when standard tangential borders are used. Incidental LAD
      artery doses remain with supine breast tangential radiation therapy.

PMID- 24674322
TI  - Requirement of percutaneous endoscopic gastrostomy tube placement in head-and
      neck cancer treated with definitive concurrent chemoradiation therapy: An
      analysis of clinical and anatomic factors.
AB  - PURPOSE: There is significant variation in recommendation for percutaneous
      endoscopic gastrostomy (PEG) tube placement in patients undergoing definitive
      chemoradiation therapy (CRT) for locally advanced squamous cell carcinoma of the
      head and neck (LAHNC), with some clinicians globally recommending prophylactic
      PEG and others waiting until toxicity has occurred. The present study was
      conceived to identify specific factors associated with PEG requirement, in a
      population of LAHNC patients who did not have up-front PEG placement. METHODS AND
      MATERIALS: Using a quality assurance database, we identified patients with
      oropharyngeal (ORP) or laryngeal-hypopharyngeal (LHP) LAHNC who were treated with
      CRT for inclusion in a cohort study of factors impacting PEG placement.
      Eligibility included stage III/IV squamous cell carcinoma of ORP and LHP.
      Patients were excluded if they had a PEG placement prior to commencement of CRT.
      The primary endpoint compared across groups was PEG placement, and multivariate
      analysis of factors was performed. RESULTS: We identified 107 patients with LAHNC
      who did not receive PEG tubes prior to treatment. After treatment initiation, 41%
      of patients with ORP tumors required PEG placement during treatment compared with
      16% of LHP patients (P = .03). After adjusting for covariates, multivariate
      analysis revealed that the only predictor for PEG placement was ORP primary (odds
      ratio 4.77; 95% confidence interval 1.6-13.8, P = .009) using LHP as reference.
      CONCLUSIONS: Our findings suggest that the patients with ORP cancers are more
      likely to require PEG placement during treatment and should be considered for
      prophylactic PEG placement, while LHP sites were associated with lower likelihood
      of PEG requirement. The primary reason for this difference appears to be severity
      of pharyngitis; proactive nutritional monitoring and supplementation should be
      implemented early. Patients with pretreatment risk stratification for PEG
      placement in LAHNC may improve quality of care and avoid unnecessary treatment
      breaks.

PMID- 24674323
TI  - Adjuvant hypofractionated intensity modulated radiation therapy after resection
      of regional lymph node metastases in patients with cutaneous malignant melanoma
      of the head and neck.
AB  - PURPOSE: To evaluate outcomes in patients with malignant melanoma of the head and
      neck with resected regional lymph node (LN) metastases treated with adjuvant
      hypofractionated intensity modulated radiation therapy (IMRT). METHODS AND
      MATERIALS: A retrospective review was performed of 46 patients with malignant
      melanoma of the head and neck with regional LN metastases treated with
      lymphadenectomy and adjuvant IMRT. Patients underwent neck dissection (n = 42) or
      local excision (n = 4) for regional metastases at initial diagnosis (n = 19) or
      recurrence (n = 27). Adjuvant IMRT was delivered twice per week over 2.5 weeks
      for a total dose of 30 Gray (Gy) in 5 fractions. Acute and late adverse events
      were recorded using the Common Toxicity Criteria for Adverse Events version 4.
      Site of first recurrence was defined as local-regional (LR, above the clavicles)
      or distant. Overall survival, disease-free survival, and disease recurrence risks
      were determined using Kaplan-Meier estimates. RESULTS: The median follow-up in
      living patients was 2.8 years (range, 0.2-6.9). Most patients experienced acute
      grade 1-2 dermatitis (80%) and mucositis (85%). One patient (2%) experienced an
      acute grade 3 adverse event. Seven patients (16%) experienced late grade 2
      adverse events. No patient experienced grade 3 or higher late adverse events.
      Site of first recurrence was LR alone (n = 5), both LR and distant (n = 1), and
      distant alone (n = 25). Five of the 6 LR recurrences were inside the IMRT
      planning target volume (PTV). In-PTV and total LR control at 3 years were 85% and
      76%, respectively. Overall survival and disease-free survival at 3 years were 63%
      and 25%, respectively. CONCLUSIONS: Adjuvant hypofractionated IMRT (30 Gy in 5
      fractions) was associated with a high rate of in-PTV control and a low risk of
      serious adverse events.

PMID- 24674324
TI  - Excluding either gross tumor volume or planning target volume from the normal
      lung volume in lung cancer irradiation: Evaluation of the dosimetric impact.
AB  - PURPOSE: When evaluating dosimetric parameters predictive of lung toxicity in
      lung cancer, the total lung volume can be defined to exclude the gross tumor
      volume (lung-GTV) or to exclude the planning target volume (lung-PTV). The
      purpose of the study was to evaluate the impact of these 2 types of delineation
      on the dosimetric parameters V20, V30, and mean lung dose (MLD). METHODS AND
      MATERIALS: We analyzed 69 patients with lung cancer treated with 3-dimensional
      radiation therapy. Normal lung volume was defined using 2 modalities of
      delineation: lung-GTV and lung-PTV. The lung volume inside the PTV, but outside
      the GTV, corresponded to the margins within the lung parenchyma applied to the
      GTV and the clinical target volume (CTV) to obtain the PTV. This volume
      (expressed in percentage of total lung volume) increases with the following: (1)
      the margins (GTV to CTV and CTV to PTV) increase within the lung parenchyma; (2)
      the GTV increases; and (3) the total lung volume decreases. RESULTS: Mean
      reduction of lung volume was 5.1% (range, 1.4-10.0). With the delineation lung
      PTV rather than lung-GTV, the mean reduction was 3.1% (P < 10(-7)), 3.3% (P < 10(
      7)), and 2.1 Gy (P < 10(-7)) for V20, V30, and MLD, respectively. These
      reductions correlated strongly with reduction of lung volume (r(2) range, 0.89
      0.96). For 25% of patients having greater reduction of lung volume (high margins,
      high tumor volume, small lung volume), reduction of V20 ranged from 4.5%-6.3%,
      reduction of V30 ranged from 4.6%-7.0%, and reduction of MLD ranged from 2.9 Gy-4
      Gy. CONCLUSIONS: The dosimetric parameters V20, V30, and MLD are reduced with the
      delineation using lung-PTV rather than lung-GTV. These reductions correlate with
      lung volume in the PTV and can be significant.

PMID- 24674325
TI  - Proton beam therapy for the treatment of prostate cancer.
AB  - Proton beam therapy (PBT) offers the potential of dose escalation to target
      tissue while decreasing toxicity through unique physical dose deposition
      characteristics. PBT has been used to treat prostate cancer for several decades;
      however, recent enhancements in availability and treatment delivery have peaked
      interest in this technology among radiation oncologists, industry experts, and
      prostate cancer patients. As a result, the importance of understanding the
      collective experience and technical aspects of PBT delivery has become
      increasingly important in radiation medicine. This review article is intended to
      critically review the literature on PBT for localized prostate cancer, discuss
      the fundamentals of PBT treatment planning, and describe the continued
      development of proton beam technology for the treatment of prostate cancer. 

PMID- 24674326
TI  - Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression
      correlates with shorter survival in patients with early stage gastric
      adenocarcinoma.
AB  - BACKGROUND: Yin Yang 1 (YY1) is a transcription factor that regulates diverse
      biological processes and increasing recognized to have important roles in
      carcinogenesis. The function and clinical significance of YY1 in gastric
      adenocarcinoma (GAC) have not been elucidated. METHODS: In this study, the
      functional role of YY1 in gastric cancer was investigated by MTT proliferation
      assays, monolayer colony formation, cell cycle analysis, signaling pathway
      analysis, Western blot analysis and in vivo study through YY1 knockdown or
      overexpression. Immunohistochemical study with YY1 antibody was performed on
      tissue microarray consisting of 247 clinical GAC samples. The clinical
      correlation and prognosis significance were evaluated. RESULTS: YY1 expression
      was up-regulated in gastric cancer cell lines and primary gastric cancers.
      Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation
      and apoptosis. Ectopic YY1 expression enhanced cell proliferation in vitro and in
      vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by
      inhibiting Wnt/beta-catenin pathway, whereas its overexpression exerted oncogenic
      property by activating Wnt/beta-catenin pathway. In primary GAC samples, YY1
      nuclear expression correlated with shorter survival and predicted poor prognosis
      in early stage GACs. CONCLUSION: Our data demonstrated that YY1 contributes to
      gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as
      a poor prognostic marker and possibly as a potential therapeutic target.

PMID- 24674327
TI  - Investigation of factors affecting the six-minute walk test results in
      hemodialysis patients.
AB  - Renal anemia, uremic myopathy, and malnutrition are some of the factors that
      affect the results of the 6-minute walk test (6MWT) in hemodialysis patients. We
      hypothesized that skeletal muscle dysfunction caused by skeletal myolysis,
      protein hypercatabolism, and mitochondrial deficiency are strongly related
      factors. The purpose of this study was to clarify the factors that affect the
      6MWT results in hemodialysis patients to assess their exercise tolerance. The
      study included 43 outpatients from the hemodialysis unit. The 6MWT was performed,
      and knee extension strength, 1-leg standing time, and grip were measured. In
      addition, the subjects' characteristics such as age, preexisting coronary artery
      disease, hemoglobin level, total iron binding capacity, serum albumin level,
      creatinine generation rate, and normalized protein catabolic rate were
      investigated. A stepwise multiple regression model was used to examine the
      factors affecting the 6MWT results. Multiple regression analysis revealed that
      knee extension strength (beta=0.446, P=0.001), total iron binding capacity (beta=
      0.299, P=0.021), and preexisting coronary artery disease (beta=-0.272, P=0.035)
      significantly affected the 6MWT results (R=0.66, R(2)=0.44). The 6MWT in
      hemodialysis patients was strongly affected by muscle strength, iron deficiency
      anemia, and preexisting coronary artery disease, suggesting that resistance
      training is important for improving 6MWT results. Our findings indicate that iron
      deficiency and cardiac function should be assessed before exercising or
      undergoing an exercise tolerance test.

PMID- 24674328
TI  - [Practice uptake in France before and after the 2010 French guidelines on kidney
      cancer].
AB  - INTRODUCTION AND OBJECTIVE: Compared to the 2007 edition, the 2010 French
      urological association onco-urology guidelines boarded the indications of partial
      nephrectomy (PN) as long as the procedure is technically feasible. The aim of
      this study was to assess national practice with respect to kidney surgery in the
      2 years before and after current guidelines. MATERIALS AND METHODS: The national
      database of the Agence Technique de l'Information sur l'Hospitalisation (ATIH)
      was queried for procedures performed between 2009 and 2010 (era 1) and between
      2011 and 2012 (era 2). The coding system of the Classification Commune des Actes
      Medicaux (CCAM) was used to extract kidney related procedures. For each era,
      procedures were sorted into partial versus radical nephrectomy (RN),
      laparoscopic/robotic versus open approach, and private versus public hospital.
      The two eras were then compared. RESULTS: Overall, 28,000 and 28,907 procedures
      were reported in era 1 and 2 with mean 14,000 and 14,450 procedures per year
      respectively. PN increased from 30% to 35% (P<0.0001) between the two eras. This
      uptake was similar in public and private hospitals. Accordingly,
      laparoscopic/robotic approach has significantly increased between the two eras
      (35% versus 39%, P<0.0001) and even more importantly in public hospitals
      (P=0.0017). There was a significant increase in laparoscopic/robotic PN as well
      as a decrease in open RN over the years of the study period. CONCLUSION: This
      study showed the development of PN and the minimally invasive approach. Over the
      study period, minimally invasive procedure uptake was higher in public hospitals.

PMID- 24674329
TI  - [Retroperitoneal leiomyoma: a case report].
AB  - Retroperitoneal leiomyoma is a rare benign tumor of the retroperitoneum. We
      report a clinical case of a 43-year-old patient, who suffered from back pain and
      weight loss. Imaging revealed a retroperitoneal mass, then the patient had a
      total excision of the tumor. Histological examination of the surgical specimen
      concluded to retroperitoneal leiomyoma. The evolution was good without recurrence
      after 12 months. 

PMID- 24674330
TI  - [Salvage radical prostatectomy for brachytherapy failure: preliminary results].
AB  - OBJECTIVES: Analysis of preliminary results in six patients operated by second
      line (salvage) radical prostatectomy for local recurrence after low-dose
      brachytherapy. PATIENTS AND METHODS: Since January 2009, six patients had an open
      salvage radical prostatectomy with a lymph node dissection and without
      neurovascular bundles preservation for a low-dose I125 brachytherapy failure.
      Local recurrence was confirmed by trans-rectal biopsy or TURP. All the patients
      had PSA increase or lower urinary tract symptoms. Bone scan and pelvis MRI were
      performed to detect a locally advanced disease, a lymph node involvement or the
      presence of bone metastasis. Pathology reports and PSA level at 1, 3, 6 and 12
      months were analyzed. RESULTS: Salvage radical prostatectomy with lymph node
      dissection was performed in all patients without major complications. The PSA
      level was below 0.1 ng/mL in five out of six patients at 1 and 3 months. The only
      case of persistent PSA is treated by androgen deprivation in a pT3b N1 patient.
      CONCLUSION: Salvage radical prostatectomy after brachytherapy failure was
      feasible with a limited perioperative morbidity. This second-line curative
      treatment in a selected group of patients should be kept in mind. Our early
      results looked promising.

PMID- 24674331
TI  - [Advanced prostate cancer in Senegal. Clinical aspects at the General Hospital of
      Grand Yoff].
AB  - Prostate cancer is a common disease, which continues to be discovered at advanced
      stages in Africa, despite improved diagnostic tools. AIM: The authors report the
      experience of the Department of Urology, General Hospital of Grand Yoff Dakar in
      the diagnostic of advanced prostate cancer. MATERIAL: This was a retrospective
      descriptive study on patients followed for advanced prostate cancer during the
      period from January 1st, 2004 to May 31st, 2010. RESULTS: There were 102 people
      aged from 51 to 96 years with an average of 71 +/- 9 years. A comorbid condition
      was associated in 24.5 % of cases. The circumstances of discovery were pain (32
      cases), neurological signs (17 cases), and urinary disorders. DRE had objectified
      an abnormality in all patients. The serum levels of prostate specific antigen
      ranged from 5.88 ng/mL to 21,660 ng/mL, with an average of 1447.57 +/- 812 ng/mL.
      A prostate biopsy was performed in 44 patients and prostatic adenocarcinoma was
      found in 97.7 % of cases with Gleason scores greater than 7 (33 cases). We found
      different metastatic sites at vertebral column (23 cases), at lung (14 cases),
      and on pelvic bones (11 cases). CONCLUSION: The prostate cancer is a serious
      condition with high morbidity and mortality. The diagnosis is not made early in
      developing countries. We need a strategic plan to improve the early screening and
      we should develop supportive care too because of the high number of advanced
      cases diagnosed in our context.

PMID- 24674332
TI  - [Management of rectourethral fistulas with the York Mason procedure: surgical
      techniques and outcomes].
AB  - OBJECTIVE: To report our experience for the management of urethro-rectal fistula
      by the York Mason technique. PATIENTS AND METHODS: We retrospectively analyzed
      the data of patients treated surgically for FUR by the technique of York Mason,
      between 2000 and 2012. RESULTS: Seventeen patients were included in the study.
      All patients had a bowel diversion before surgery. We observed four recurrences
      of FUR (23.5%). Recurrences occurred in a radiation field for two patients and in
      a oncologic recurrence for 1 patient. The fourth recurrence was treated by a
      second procedure of York Mason successfully. CONCLUSION: In our study, the York
      Mason technique was safe and reproducible for the treatment of FUR. The main
      factor of failure was a history of pelvic radiotherapy.

PMID- 24674333
TI  - [Family refusal of organ donation: a retrospective study in a French organ
      procurement center].
AB  - OBJECTIVES: In France, organ donation refusal rates approach 32% of eligible
      brain deaths. Outright family refusal represents the primary barrier reason for
      declining organ donation. This retrospective study evaluated factors influencing
      this decision. MATERIAL AND METHODS: A retrospective chart review at Lille
      Hospital, France, was conducted on brain-death patients eligible for organ
      donation between 2010 and 2011. Data were collected regarding patient
      characteristics, death conditions and reasons for refusal based upon family
      interview. Descriptive statistic analyses were conducted to identify
      circumstances associated with family refusal. RESULTS: Of 227 eligible organ
      donors identified, 70 families (30.8%) refused organ donation. The most frequent
      reason for refusal was desire to keep the body's wholeness (46.3%), followed by
      religion (16.4%), mistrust of the medical community (13.4%), and revolt against
      society (6%). The most common causes of death associated with refusal were
      brutality and suddenness of death (44.8%), early age (23.9%), denial of death
      (17.9%), and the family culpability (11.9%). In 30% of cases, the family followed
      the deceased's wishes before his death. CONCLUSION: Family refusal remains a
      significant factor associated with the approximately one third of declined
      eligible organ donations. This retrospective analysis suggested that the most
      important cause for refusal was a desire to keep the body's wholeness, and the
      brutality and suddenness of the potential donor's death. Additional research
      addressing these factors, and their underlying causes, paired with measures to
      improve professional training and public awareness are warranted to improve organ
      donation rates.

PMID- 24674334
TI  - [Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment
      and results of 100 cases].
AB  - AIM: To assess short term morbidity and renal function after robotic laparoscopic
      living donor nephrectomy. PATIENTS AND METHODS: We performed a retrospective
      analysis of 100 consecutives patients undergoing a robotic laparoscopic living
      donors nephrectomy. We analyzed isotopic measure of the renal function before and
      4 months after surgery, the side, the number of arteries, the blood loss, the
      operative time and warm ischemia time. In the outcomes, we collected the
      complications, the length of stay, and for the receiver, the renal function
      recovery time, dialysis, survival and renal function at one year. RESULTS: Left
      kidney nephrectomy was performed in 85 patients and we observed 25 multiples
      renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and
      warm ischemia time were respectively 174 +/- 30 and 4.8 +/- 1.7 minutes. Seven
      complications occured, with 2 major (Clavien-Dindo System). Mean length of stay
      was 5.1 +/- 1.9 days. Mean glomerular filtration decrease was 26% and remains
      stable at one year after surgery. Grafts had an immediate renal function recovery
      for 99%, and were all functional after one year, with mean MDRD clearance of 57
      +/- 14mL/min. CONCLUSION: Robotic procedure in laparoscopic living donor
      nephrectomy seems to guarantee low morbidity and the stability of the renal
      function decrease of 26%.

PMID- 24674335
TI  - [Renal colic in pregnancy: series of 103 cases].
AB  - PURPOSE: To evaluate the management of renal colic in pregnant woman in our
      hospital. MATERIAL AND METHODS: A retrospective study of 103 pregnant patients,
      hospitalized for back pain of renal colic type, associated or not with a urinary
      tract infection, between January 2005 and October 2010. Three groups of patients
      were identified from the initial clinical and paraclinical (ultrasound). Group I
      involved patients with dilatation of the renal cavities associated with septic
      syndrome, they received analgesic treatment and empiric antibiotic therapy. Group
      II involved patients with dilatation of the renal cavities isolated, without
      fever, they received only analgesic treatment. Group III involved patients
      without dilatation of the renal cavities, they received analgesic treatment and
      antibiotics in case of fever, and then another cause of pain was sought. RESULTS:
      The renal colic was due to a stone in 19.4 % of cases. A urinary infection was
      associated in 28 % of patients. Ultrasond was sufficient to confirm the diagnosis
      in 96 % of cases. In 4 % of cases, MRI or low-dose CT were necessary. Therapeutic
      management based on analgesic treatment, associated with probabilistic
      antibiotherapy or adapted in case of documented infection, allowed sedation of
      pain in two-third of cases. In case of failure or signs of severity, the urinary
      diversion by a double J stent was efficient, without consequences on pregnancy
      issue. One stone was treated by ureteroscopy during pregnancy without
      complication. CONCLUSION: The management of renal colic in pregnant woman based
      on ultrasound diagnosis, symptomatic treatment and urinary diversion by double J
      stent in case of failure therefore seemed quite sure on mother and fetus.

PMID- 24674336
TI  - [Sarcomatoid renal cell carcinoma: follow-up of a series of 23 patients].
AB  - OBJECTIVE: To describe survival data and prognostic factors in a population of
      renal cell carcinoma with sarcomatoid renal carcinoma. PATIENTS AND METHODS: We
      reviewed the files of 950 patients treated for malignant renal tumor in two
      centers between January 2002 and December 2011. Patients with sarcomatoid renal
      cell carcinoma were extracted. Demographic data, treatments, histopathological
      and survival data as well as prognostic factors were analyzed. RESULTS: Twenty
      three patients (2.4%) with 65% of men were included with a mean age of 62.8 years
      (41; 82). Median ECOG PS was 1 (0; 3) and median Karnofsky PS was 80% (40-100).
      Median tumor size was 100mm (30; 190). Eight patients (35%) were metastatic at
      diagnosis. An initial surgical treatment was performed in 22 patients (95.7%).
      Tumors were clear cell carcinoma in 19 cases (82.6%). TNM tumor stage was greater
      than 2 in 81.8% of cases. Median rate of sarcomatoid component was 50% (10; 100).
      In univariate analysis, the existence of initial metastasis and microvascular
      invasion were predictors of specific survival. In multivariable analysis, the
      only predictor was the initial existence of metastasis. A progression was
      observed in metastatic mode in 78% of patients within a median of 7 months. The
      median disease-specific survival was 18 months. CONCLUSION: Sarcomatoid renal
      cell carcinomas were aggressive tumors with a median progression-free survival of
      7 months and a median disease-specific survival of 18 months. Prognostic factors
      were comparable to high-risk renal cell carcinomas. LEVEL OF EVIDENCE: 5.

PMID- 24674337
TI  - [Impact of surgery in the management of pancreatic metastases of renal cell
      cancer].
AB  - INTRODUCTION: Incidence of renal cell carcinoma (RCC) is increasing over the 25
      last years. Pancreatic metastases of RCC are rare. The aim of this work was to
      study overall survival of patients operated for pancreatic metastases of RCC in
      Montpellier cancer institute. PATIENTS AND METHODS: Between 2000 and 2012, a
      retrospective monocentric study was performed at Montpellier cancer institute. We
      evaluated the outcomes of curative pancreatic metastases from renal primary and
      the impact of targeted therapies. RESULTS: Thirty-eight patients were treated in
      our center for pancreatic metastases of RCC. Twelve patients had a curative
      surgery of metachronous pancreatic metastases. Four patients were without
      recurrence after pancreatic resection (33.3%). None had adjuvant therapy. Six
      patients were treated by targeted therapies, because of metastatic progression.
      Five of 6 died, the sixth evolved with targeted therapies by thyrosine kinase
      inhibitor. Average deadline between appearance of metastases and death was 89.9
      months for operated patients. Average deadline between appearance of c metastases
      and death was 33.1 months for the others (P=0.004). CONCLUSION: Surgical
      treatment of pancreatic metastases should increase life expectancy of patients.
      Others studies are necessary to prove the impact of targeted therapies in
      metastatics patients in this indication. LEVEL OF EVIDENCE: 5.

PMID- 24674338
TI  - [Clinical impact of the intravesical prostatic protrusion: a review by the LUTS
      committee of the French Urological Association].
AB  - INTRODUCTION: Intravesical prostatic protrusion (IPP) is a protrusion of the
      lateral and/or median prostatic lobes into the bladder lumen. IPP can be
      estimated by suprapubic ultrasound. METHODS: A literature search was conducted in
      Pubmed/MEDLINE database using the following keywords: intravesical prostatic
      protrusion; benign prostatic enlargement; treatment outcome; ultrasonography.
      RESULTS: There are 3 grades of IPP: grade 1, 2 and 3 respectively if IPP <= 5mm,
      if 5-10mm, and if >10mm. IPP was a better prognosis factor than PSA and prostate
      volume for bladder outlet obstruction (BOO) with a sensibility of 80% and a
      sensitivity of 68% for grade 3. The progression risk of BOO increased with IPP
      (grade 1: OR=5.1 [95%CI: 1.6-16.2] and grade >= 2 OR=10.4 [95%CI: 3.3-33.4]). IPP
      was a predictive marker of failure of trial off catheter in patients with acute
      urinary retention with a 6 folds higher risk for grades >= 2. IPP was a prognosis
      factor for tamsulosine efficacy: 78% of patients with grade <= 2 had an
      improvement >35% of the IPSS-score versus 58% for grade >3 (P<0.01). Patients
      with grade >3 and a PV< 40cc had a poorer response to tamsulosine. After TURP,
      IPSS was more improved for grade >= 1 with an OR=3.43 (95%CI: 1.03-11.44,
      P=0.045). CONCLUSION: IPP can be a useful marker for the management of LUTS/BPH.

PMID- 24674339
TI  - [Update for the management of kidney stones in 2013. Lithiasis Committee of the
      French Association of Urology].
AB  - Since the publication of the latest recommendations of the Lithiasis Comity of
      the French Association of Urology (CLAFU) on the management of ureteral and renal
      stones, practices have evolved. This text provides an update for the treatment of
      kidney stones. It is especially the important advances in the field of laser
      ureterorenoscopy that changed practices. Percutaneous nephrolithotomy has been
      enriched by technical modifications and extracorporeal shockwave lithotripsy
      confirmed its predominant place in the first line of treatment. For stones less
      than 20mm, extracorporeal lithotripsy remains the standard, but in some cases the
      possibility of recommending a flexible ureterorenoscopy is possible in first
      line. For stones more than 20mm, percutaneous nephrolithotomy is the standard
      treatment, but optional flexible ureteroscopy and extracorporeal lithotripsy are
      possible. The treatment carried out, collect the stone fragments for a morpho
      constitutional analysis and achieve a metabolic evaluation is necessary, to
      investigate etiologic and give dietary advices to prevent recurrence. 

PMID- 24674340
TI  - Role of filler and functional group conversion in the evolution of properties in
      polymeric dental restoratives.
AB  - OBJECTIVES: To examine effects of shrinkage and modulus on the dynamic
      development of shrinkage stress as a function of methacrylate conversion and
      filler loading in a model photocurable dimethacrylate-based resin with a
      silanized barium glass filler. METHODS: BisGMA/TEGDMA samples with filler loading
      levels of 0-70wt% were evaluated. Irradiation times and intensities were varied
      to achieve a wide range of conversion. Shrinkage stress measurements were
      accompanied with real-time conversion monitoring, while shrinkage and modulus
      measurements were made at different static conversion points. RESULTS: Shrinkage
      increased nearly linearly with respect to conversion, while for a given value of
      conversion, it decreased proportionally with increasing filler content. Modulus
      advanced in an exponential fashion with conversion and also increased
      incrementally with filler content; however, modulus values rose
      disproportionately rapidly for the highest filler loading. At either high or low
      filler loading levels, stress at limiting conversion, which was inversely
      proportional to the filler load, was high while at an intermediate filler
      content, a minimum in stress was observed due to the combined effects of filler
      based shrinkage reduction, restricted limiting conversion and only moderately
      enhanced modulus. The level of polymerization stress predicted from the
      conversion-indexed shrinkage and modulus measurements over-estimated the
      experimental stress states as modulus evolved due to system compliance that to
      some degree mimics the clinical situation presented by photocuring bonded
      composite restorations. Significance Measurement of monomer conversion provides a
      common basis by which different material properties can be rationally compared.

PMID- 24674341
TI  - The reciprocity law concerning light dose relationships applied to BisGMA/TEGDMA
      photopolymers: theoretical analysis and experimental characterization.
AB  - OBJECTIVES: A model BisGMA/TEGDMA unfilled resin was utilized to investigate the
      effect of varied irradiation intensity on the photopolymerization kinetics and
      shrinkage stress evolution, as a means for evaluation of the reciprocity
      relationship. METHODS: Functional group conversion was determined by FTIR
      spectroscopy and polymerization shrinkage stress was obtained by a tensometer.
      Samples were polymerized with UV light from an EXFO Acticure with 0.1wt%
      photoinitiator. A one-dimensional kinetic model was utilized to predict the
      conversion-dose relationship. RESULTS: As irradiation intensity increased,
      conversion decreased at a constant irradiation dose and the overall dose required
      to achieve full conversion increased. Methacrylate conversion ranged from 64+/-2%
      at 3mW/cm(2) to 78+/-1% at 24mW/cm(2) while the final shrinkage stress varied
      from 2.4+/-0.1MPa to 3.0+/-0.1MPa. The ultimate conversion and shrinkage stress
      levels achieved were dependent not only upon dose but also the irradiation
      intensity, in contrast to an idealized reciprocity relationship. A kinetic model
      was utilized to analyze this behavior and provide theoretical conversion profiles
      versus irradiation time and dose. SIGNIFICANCE: Analysis of the experimental and
      modeling results demonstrated that the polymerization kinetics do not and should
      not be expected to follow the reciprocity law behavior. As irradiation intensity
      is increased, the overall dose required to achieve full conversion also
      increased. Further, the ultimate conversion and shrinkage stress that are
      achieved are not dependent only upon dose but rather upon the irradiation
      intensity and corresponding polymerization rate.

PMID- 24674342
TI  - Chipping fracture resistance of denture tooth materials.
AB  - OBJECTIVE: The applicability of the edge chipping method to denture tooth
      materials was assessed. These are softer materials than those usually tested by
      edge chipping. The edge chipping fracture resistances of polymethylmethacrylate
      (PMMA) based and two filled resin composite denture tooth materials were
      compared. METHODS: An edge chipping machine was used to chip rectangular blocks
      and flattened anterior denture teeth. Force versus edge distance data were
      collected over a broad range of forces and distances. Between 20 and 65 chips
      were made per condition depending upon the material, the scatter, and the
      indenter type. Different indenter types were used including Rockwell C, sharp
      conical 120(o), Knoop, and Vickers. The edge toughness, Te, was evaluated for
      different indenter types. RESULTS: The edge chipping data collected on the blocks
      matched the data collected from flattened teeth. High scatter, particularly at
      large distances and loads, meant that many tests (up to 64) were necessary to
      compare the denture tooth materials and to ascertain the appropriate data trends.
      A linear force-distance trend analysis was adequate for comparing these
      materials. A power law trend might be more appropriate, but the large scatter
      obscured the definitive determination of the precise trend. Different indenters
      produce different linear trends, with the ranking of: sharp conical 120(o),
      Rockwell C, and Knoop, from lowest to highest edge toughness. Vickers indenter
      data were extremely scattered and a sensible trend could not be obtained. Edge
      toughness was inversely correlated to hardness. SIGNIFICANCE: Edge chipping data
      collected either from simple laboratory scale test blocks or from actual denture
      teeth may be used to evaluate denture materials. The edge chipping method's
      applicability has been extended to another class of restorative materials.

PMID- 24674343
TI  - Quantum chemical assessment of benzimidazole derivatives as corrosion inhibitors.
AB  - BACKGROUND: The majority of well-known inhibitors are organic compounds
      containing multiple bonds and heteroatoms, such as O, N or S, which allow
      adsorption onto the metal surface. These compounds can adsorb onto the metal
      surface and block active surface sites, reducing the rate of corrosion. RESULTS:
      A comparative theoretical study of three benzimidazole isomers, benzimidazole
      (BI), 2-methylbenzimidazole (2-CH3-BI), and 2-mercaptobenzimidazole (2-SH-BI), as
      corrosion inhibitors was performed using density functional theory (DFT) with the
      B3LYP functional basis set. CONCLUSIONS: Nitro and amino groups were selected for
      investigation as substituents of the three corrosion inhibitors. Nitration of the
      corrosion inhibitor molecules led to a decrease in inhibition efficiency, while
      reduction of the nitro group led to an increase in inhibition efficiency. These
      aminobenzimidazole isomers represent a significant improvement in the inhibition
      efficiency of corrosion inhibitor molecules.

PMID- 24674344
TI  - Congenital absence of the internal carotid artery: an unusual cause of
      asymmetrical diabetic retinopathy.

PMID- 24674345
TI  - Transoral laser microsurgery in previously irradiated patients with laryngeal
      cancer.
AB  - PURPOSE: Early laryngeal cancer is successfully managed with transoral laser
      microsurgery. Previously radiated patients may experience more post-operative
      complications. We investigate disease-free survival and secondarily prolonged
      pain and chondronecrosis. MATERIALS AND METHODS: Retrospective review of 52
      patients undergoing transoral laser microsurgery after previous radiation.
      RESULTS: Mean disease-free survival was 36.7 months. Overall disease-free
      survival was 57.6% at 3-year and 48.4% at 5-year follow-up, with no significant
      difference between surgery within as opposed to after 60 months of radiation or
      within as opposed to after 12 months of radiation. Thirteen patients, all with
      surgery within 60 months of radiation, experienced prolonged pain. Twelve
      experienced chondronecrosis, all within 12 months of surgery. CONCLUSION:
      Transoral laser microsurgery for early laryngeal cancer is an adequate
      therapeutic option in patients with history of radiation with comparable disease
      free survival to other reports. Patients undergoing transoral laser microsurgery
      within 60 months of radiation treatment are more likely to experience prolonged
      pain.

PMID- 24674346
TI  - Perinatal vertical transmission of antibiotic-resistant bacteria: a systematic
      review and proposed research strategy.
AB  - BACKGROUND: Antibiotic-resistant bacteria contribute to both early- and late
      onset sepsis and outbreaks in neonatal intensive care units (NICUs). The extent
      to which vertical transmission of these resistant bacteria contributes to
      colonisation or infection of vulnerable infants in NICUs is unclear. Risk factors
      for vertical transmission of antibiotic-resistant bacteria are not well
      described. OBJECTIVES: To identify studies describing vertical transmission of
      antibiotic-resistant bacteria, risk factors for transmission and the impact of
      colonisation on neonatal outcomes. SEARCH STRATEGY: EMBASE, CINAHL, Cochrane,
      PubMed, and MEDLINE databases were searched using selected terminology. Titles
      and abstracts were screened by two reviewers. Selected papers were reviewed in
      full by two individuals to ascertain whether they fulfilled the inclusion
      criteria. SELECTION CRITERIA: Any original article investigating perinatal
      vertical transmission of antibiotic-resistant bacteria between a mother and
      neonate was included. DATA COLLECTION AND ANALYSIS: Data were extracted on study
      design, organism, antibiotic resistance, and means of ascertaining vertical
      transmission. MAIN RESULTS: Five papers out of 4839 titles fulfilled the
      inclusion criteria. Four studies were predominantly observational and one was a
      case report. Each demonstrated perinatal transmission. No study reported risk
      factors for the transmission of resistant bacteria or the impact of colonisation
      on neonatal outcomes. AUTHOR'S CONCLUSIONS: There is an absence of research into
      the perinatal transmission of resistant organisms despite the potential
      implications of such a situation. We outline objectives that need to be addressed
      in future research and describe a study design to ascertain the prevalence and
      risk factors for vertical transmission.

PMID- 24674347
TI  - [False aneurysm of the outflow tract of the right ventricle secondary to candida
      mediastinitis after surgical repair of tetralogy of Fallot: rare complication of
      exceptional cause!].

PMID- 24674349
TI  - Are we estimating the adverse effects of shock-wave lithotripsy on a faulty
      scale?
AB  - The adverse effect of shock-wave lithotripsy (SWL) for renal stones on blood
      pressure is currently defined as its post-treatment increase. On the contrary, we
      hypothesize that even mild, unilateral renal obstruction initiates an increase in
      blood pressure. Then, in absence of treatment-induced injury, the stone removal
      should decrease the blood pressure. We derived the formula to assess the expected
      change in the mean arterial pressure following relief of renal obstruction
      without affecting the kidney functions. The predictions were well replicated in
      the cohort of patients with renal stone treated with parenchyma-saving open
      surgery, with 6.4 mmHg decrease at 3 months. On the contrary, in SWL cohort,
      instead of the expected 4.7 mmHg decrease, the blood pressure was unchanged. In
      conclusion, the absence of decrease in blood pressure is a very common adverse
      effect of SWL, leading to an epidemiologically significant increase in the risk
      of arterial vascular events.

PMID- 24674348
TI  - The ubiquilin gene family: evolutionary patterns and functional insights.
AB  - BACKGROUND: Ubiquilins are proteins that function as ubiquitin receptors in
      eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the
      genesis of neurodegenerative diseases. However, ubiquilin functions are still
      poorly understood. RESULTS: In this study, evolutionary and functional data are
      combined to determine the origin and diversification of the ubiquilin gene family
      and to characterize novel potential roles of ubiquilins in mammalian species,
      including humans. The analysis of more than six hundred sequences allowed
      characterizing ubiquilin diversity in all the main eukaryotic groups. Many
      organisms (e. g. fungi, many animals) have single ubiquilin genes, but
      duplications in animal, plant, alveolate and excavate species are described.
      Seven different ubiquilins have been detected in vertebrates. Two of them, here
      called UBQLN5 and UBQLN6, had not been hitherto described. Significantly,
      marsupial and eutherian mammals have the most complex ubiquilin gene families,
      composed of up to 6 genes. This exceptional mammalian-specific expansion is the
      result of the recent emergence of four new genes, three of them (UBQLN3, UBQLN5
      and UBQLNL) with precise testis-specific expression patterns that indicate roles
      in the postmeiotic stages of spermatogenesis. A gene with related features has
      independently arisen in species of the Drosophila genus. Positive selection
      acting on some mammalian ubiquilins has been detected. CONCLUSIONS: The ubiquilin
      gene family is highly conserved in eukaryotes. The infrequent lineage-specific
      amplifications observed may be linked to the emergence of novel functions in
      particular tissues.

PMID- 24674350
TI  - 'Prognostic -Omic Clusters' (POCs): a novel approach to health and disease.
AB  - The concept of disease is central to modern medicine and society's concept of
      health and illness. Its recognition and nomenclature are based on correlating
      clinical syndromes, underlying morbid pathologies and pathophysiologies. This
      conceptualization is being challenged by the advances in the field of "-omics"
      (e.g. proteomics) where arrays of compounds are assayed. Complex mathematical
      algorithms of their results reveal clusters that are prognostically important,
      yet not recognized as disease states (Prognostic -Omic Clusters, -POCs). At a
      given point in time, they are termed Static-POCs. However, the dynamism of the
      body's physiology should be incorporated to this concept. This requires using the
      patterns of the rates of change of these '-omics' (Dynamic-POCs), a method used
      in ICU settings. The latter has yielded prognostically important patterns of the
      rates of change of several physiological parameters. These Static and Dynamic
      POCs will become apparent in 'healthy' individuals, and their progress ought to
      reveal unique paths of progress towards disease states. This will enable
      interventions for prevention at a very early stage. The margins between health
      and diseases will blur, and diseases as a concept will become increasingly
      redundant with major implications to clinical practice and preventive health. 

PMID- 24674352
TI  - Readability, suitability, and health content assessment of web-based patient
      education materials on colorectal cancer screening.
AB  - BACKGROUND: Colorectal cancer (CRC) screening rates in the Unites States are
      still below target level. Web-based patient education materials are used by
      patients and providers to provide supplemental information on CRC screening. Low
      literacy levels and patient perceptions are significant barriers to screening.
      There are little data on the quality of these online materials from a health
      literacy standpoint or whether they address patients' perceptions. OBJECTIVE: To
      evaluate the readability, suitability, and health content of web-based patient
      education materials on colon cancer screening. DESIGN: Descriptive study.
      SETTING: Web-based patient materials. INTERVENTIONS: Twelve reputable and popular
      online patient education materials were evaluated. Readability was measured by
      using the Flesch-Kincaid Reading Grade Level, and suitability was determined by
      the Suitability Assessment of Materials, a scale that considers characteristics
      such as content, graphics, layout/typography, and learning stimulation. Health
      content was evaluated within the framework of the Health Belief Model, a
      behavioral model that relates patients' perceptions of susceptibility to disease,
      severity, and benefits and barriers to their medical decisions. Each material was
      scored independently by 3 reviewers. MAIN OUTCOME MEASUREMENTS: Flesch-Kincaid
      Reading Grade Level score, Suitability Assessment of Materials score, health
      content score. RESULTS: Readability for 10 of 12 materials surpassed the maximum
      recommended sixth-grade reading level. Five were 10th grade level and above. Only
      1 of 12 materials received a superior suitability score; 3 materials received
      inadequate scores. Health content analysis revealed that only 50% of the
      resources discussed CRC risk in the general population and <25% specifically
      addressed patients at high risk, such as African Americans, smokers, patients
      with diabetes, and obese patients. For perceived barriers to screening, only 8.3%
      of resources discussed embarrassment, 25% discussed pain with colonoscopy, 25%
      addressed cost of colonoscopy, and none specifically mentioned the need to get
      colonoscopy when no symptoms are present. No material discussed the social
      benefits of screening. LIMITATIONS: Descriptive design. CONCLUSION: Most online
      patient education materials for CRC screening are written beyond the recommended
      sixth-grade reading level, with suboptimal suitability. Health content is lacking
      in addressing key perceived risks, barriers, and benefits to CRC screening.
      Developing more appropriate and targeted patient education resources on CRC may
      improve patient understanding and promote screening.

PMID- 24674351
TI  - Low uptake of colorectal cancer screening among African Americans in an
      integrated Veterans Affairs health care network.
AB  - BACKGROUND: African Americans have the highest incidence and mortality from
      colorectal cancer (CRC). Despite guidelines to initiate screening with
      colonoscopy at age 45 in African Americans, the CRC incidence remains high in
      this group. OBJECTIVE: To examine the rates and predictors of CRC screening
      uptake as well as time to screening in a population of African Americans and non
      African Americans in a health care system that minimizes variations in insurance
      and access. DESIGN: Retrospective cohort study. SETTING: Greater Los Angeles
      Veterans Affairs (VA) Healthcare System. PATIENTS: Random sample (N = 357) of
      patients eligible for initial CRC screening. MAIN OUTCOME MEASUREMENTS: Uptake of
      any screening method; uptake of colonoscopy, in particular; predictors of
      screening; and time to screening in African Americans and non-African Americans.
      RESULTS: The overall screening rate by any method was 50%. Adjusted rates for any
      screening were lower among African Americans than non-African Americans (42% vs
      58%; odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31-0.77). Colonoscopic
      screening was also lower in African Americans (11% vs 23%; adjusted OR 0.43; 95%
      CI, 0.24-0.77). In addition to race, homelessness, lower service connectedness,
      taking more prescription drugs, and not seeing a primary care provider within 2
      years of screening eligibility predicted lower uptake of screening. Time to
      screening colonoscopy was longer in African Americans (adjusted hazard ratio
      0.43; 95% CI, 0.25-0.75). LIMITATIONS: The sample may not be generalizable.
      CONCLUSIONS: We found marked disparities in CRC screening despite similar access
      to care across races. Despite current guidelines aimed at increasing CRC
      screening in African Americans, participation in screening remained low, and use
      of colonoscopy was infrequent.

PMID- 24674353
TI  - A novel technique for endoscopic transpapillary "mapping biopsy specimens" of
      superficial intraductal spread of bile duct carcinoma (with videos).

PMID- 24674355
TI  - Substantial increase in mutations in the genes pfdhfr and pfdhps puts
      sulphadoxine-pyrimethamine-based intermittent preventive treatment for malaria at
      risk in Burkina Faso.
AB  - OBJECTIVE: Sulphadoxine-pyrimethamine (SP) is widely used as intermittent
      preventive treatment (IPT) for malaria in pregnant women in Sub-Saharan Africa.
      There are reports of wide-spread SP resistance in countries where SP had once
      been used as a first-line treatment. It is unclear whether the development of SP
      resistance also affects countries where SP is mainly used in the context of IPT,
      as is the case in Burkina Faso. To assess the efficacy of SP-based IPT, we
      monitored the prevalence of SP conferring genetic mutations in the genes dhfr and
      dhps in Plasmodium falciparum populations in a rural area of Burkina Faso over a
      period of 13 years. METHODS: Molecular epidemiological study consisted of six
      consecutive cross-sectional surveys of rainy and dry seasons (2009-2012). Data
      from the rainy season in 2000 served as a baseline. Mutations in dhfr and dhps
      associated with SP resistance were analysed by pyrosequencing in 861 parasite
      positive samples. RESULTS: The prevalence of the SP resistance conferring triple
      dhfr mutation 51I, 59R, 108N increased from 1.3% in the rainy season of 2000 to
      35.3% in 2009, and 54.3% in 2011 (P <= 0.001). Comparing rainy and dry seasons,
      we observed an increasing step-like pattern with higher prevalence of the dhfr
      triple mutant in the respective dry season compared with the preceding rainy
      season. The proportion of the dhps 437Gly mutation in the rainy season of 2000
      was 53.2% and subsequently increased to 77.6% in 2009 (P <= 0.001). CONCLUSION:
      The increase in molecular markers linked with SP resistance jeopardises the
      efficacy of IPTp and the planned IPTi interventions in Burkina Faso, calling for
      careful monitoring of genotypic resistance markers and in vivo validation of IPT
      efficacy.

PMID- 24674354
TI  - Impact of day of admission on mortality and other outcomes in upper GI
      hemorrhage: a nationwide analysis.
AB  - BACKGROUND: Studies have reached varying conclusions regarding the association
      between day of admission and outcomes in patients with upper GI hemorrhage
      (UGIH). OBJECTIVES: To evaluate whether important outcomes in UGIH, including in
      hospital mortality, differ between patients admitted on weekends versus weekdays.
      DESIGN AND SETTING: Retrospective cohort study by using the 2009 Nationwide
      Inpatient Sample. PATIENTS: Patients were included if they were adults with a
      principal diagnosis of acute UGIH. Patients admitted between midnight Friday and
      midnight Sunday were classified as weekend admissions. MAIN OUTCOME MEASUREMENTS:
      In-hospital mortality, in-hospital endoscopy, endoscopic therapy, length of stay,
      and total hospitalization charges. RESULTS: The study included 199,008 patients
      with nonvariceal UGIH and 3251 patients with variceal UGIH. Compared with
      patients admitted on weekdays, patients with nonvariceal UGIH admitted on
      weekends had similar adjusted in-hospital mortality rates (odds ratio [OR] 1.11;
      95% confidence interval [CI], 0.93-1.30), endoscopic therapy rates (OR 0.98; 95%
      CI, 0.92-1.04), and length of stay (P = .09), but had lower early endoscopy rates
      (within 24 hours)(OR 0.64; 95% CI, 0.60-0.67), lower in-hospital endoscopy rates
      (OR 0.84; 95% CI, 0.78-0.91), and higher hospitalization charges (mean increase,
      $1558; P = .01). Patients with variceal UGIH admitted on weekends and weekdays
      did not differ in any of these outcomes. LIMITATIONS: Retrospective data,
      administrative database. CONCLUSIONS: Compared with patients admitted on
      weekdays, patients with nonvariceal UGIH admitted on weekends had similar
      mortality rates and lengths of stay, but lower endoscopy rates and higher
      hospitalization charges. Patients with variceal GI hemorrhage had similar
      outcomes regardless of day of admission.

PMID- 24674356
TI  - Selective modulation of motor cortical plasticity during voluntary contraction of
      the antagonist muscle.
AB  - A fundamental approach for resolving motor deficits in patients suffering from
      various neurological diseases is to improve the impaired cortical function
      through the modulation of plasticity. In order to advance clinical practice in
      this regard, it is necessary to better understand the interactions that occur
      between functional neuromuscular activity and the resulting cortical plasticity.
      This study tested whether the voluntary contraction of an antagonist muscle
      modulates the plasticity-like effect of continuous theta burst stimulation (cTBS)
      recorded from the agonist. The effects of various opposing torques produced by
      the antagonist were also measured. As a result, the suppressing effect of cTBS
      was enhanced by mild antagonist contraction, whereas effortful antagonist
      contraction suspended the plasticity caused by cTBS. In contrast, the antagonist
      contractions right after cTBS did not significantly influence the effect of cTBS.
      The results indicate that the antagonist activity alters the effect of cTBS,
      especially in protocols with synchronous magnetic stimulation and antagonist
      contraction. Such modulation on cTBS may be through a reciprocal mechanism within
      the motor cortex, although the spinal regulation of the motoneuronal pool cannot
      be fully excluded. The present findings are beneficial for elucidating the
      mechanism of neuromuscular control and for resolving related neurological
      disorders. 

PMID- 24674357
TI  - An editorial note: the long arm of practical radiation oncology.

PMID- 24674358
TI  - Gastrointestinal stereotactic body radiation therapy requires detailed normal
      tissue planning to prevent long-term complications.

PMID- 24674359
TI  - Patient safety improvements in radiation treatment through 5 years of incident
      learning.
AB  - PURPOSE: To quantify the impact of a comprehensive incident learning system in
      terms of safety improvements. METHODS AND MATERIALS: An incident learning system
      tailored for radiation treatment and based on published principles has been used
      consistently in our large academic cancer center for more than 5 years. In the
      adopted system, every incident, whether or not there is a resulting direct impact
      on a patient treatment, is recorded and investigated to determine basic causes.
      The scope of the program thus includes potential, or near miss, events which have
      no impact on patients but which provide valuable insights into program weaknesses
      and hence facilitate proactive measures to minimize risk. RESULTS: Analysis of
      2506 incident reports generated over a 5-year period demonstrate a substantial
      decline in actual, nonminor incidents; ie, those with a dose variation from that
      prescribed of greater than 5%. Only 49 incidents (1.95%) had an impact on
      patients. The actual incident rate at the point of treatment delivery, the most
      vulnerable point in our process, has also decreased. The system has provided
      rapid feedback to monitor several initiatives including implementation of new
      technology and several new treatment techniques. Using the evidence provided by
      these incident reports, strategies were developed by a multidisciplinary team to
      address system weaknesses. Interventions introduced include several human error
      reduction strategies including forcing functions and constraints to improve
      system resilience. CONCLUSIONS: Our results demonstrate that effective use of an
      incident learning system will strongly encourage the reporting of incidents,
      whether or not they directly impact a patient, and serve as a proactive means of
      enhancing safety and quality. As a side benefit, addressing and overcoming the
      cultural barriers between the 3 professional groups involved in radiation
      treatment has resulted in an improvement in the safety culture in our center.

PMID- 24674360
TI  - Patient safety improvement efforts: How do we know we have made an impact?

PMID- 24674361
TI  - Comparison of setup accuracy and intrafraction motion using stereotactic frame
      versus 3-point thermoplastic mask-based immobilization for fractionated cranial
      image guided radiation therapy.
AB  - PURPOSE: Prospectively compare patient setup accuracy and intrafraction motion of
      a standard 3-point thermoplastic mask with the Gill-Thomas-Cosman relocatable
      stereotactic frame, during fractionated cranial radiation therapy using the
      ExacTrac system (Brainlab AG Feldkirchen, Germany) for daily online correction.
      METHODS AND MATERIALS: The number of fractions with all postcorrection and post
      treatment errors <2 mm was assessed in 21 patients undergoing fractionated
      stereotactic radiation therapy (13 frame setup, 8 mask setup) using daily online
      correction. Achievable patient setup accuracy and total intrafraction motion were
      evaluated. The relative contributions of movement during floor rotation and
      patient movement to intrafraction motion were calculated. RESULTS: With daily
      online correction, patient setup margins can be reduced from 1, 5, and 4 mm in
      the lateral, longitudinal, and vertical axes for mask setup and from 1-2, 2, and
      1 mm, respectively, for frame setup to <1 mm isotropically for either
      immobilization system. Intrafraction movement was small for frame setup (mean
      [SD], -0.3 [0.3], -1.1[0.4], and -0.2 [0.6] in lateral, longitudinal and vertical
      axes, respectively; maximum, -2.7 mm [longitudinal axis]), and mask-setup (mean
      [SD], -0.4 [0.5], -0.8 [0.7], and 0.0 [0.3], respectively; maximum, -2.0 mm
      [longitudinal axis]) and is mainly due to floor rotation. Postcorrection and post
      treatment errors were all <2 mm in 95% and 99% of fractions in the mask and
      frame, respectively, meeting the criteria for a 3-mm clinical target volume
      planning target volume margin for either immobilization method. CONCLUSIONS:
      Daily online correction can compensate for less precise immobilization and
      permits stereotactic margins to be used for standard thermoplastic masks without
      the need for specialized mask systems.

PMID- 24674362
TI  - Kinetics of myxoid liposarcoma radiation response and effects on radiation dose
      delivery.
AB  - PURPOSE: Recent reports have described the radioresponsiveness of myxoid
      liposarcomas (MLS). We sought to describe the kinetics of these changes during
      image guided radiation therapy and determine the effect of these changes in
      volume on the dose distribution. METHODS AND MATERIALS: We reviewed the images of
      all patients with the diagnosis of MLS who had undergone preoperative radiation
      therapy using image guidance at our institution. All patients received a dose of
      50 Gy in 25 fractions. Tumor volume was measured on each patient's computed
      tomographic (CT) simulation scan, on weekly CT images performed for image
      guidance, as well as on postradiation imaging. Dose distributions were
      recalculated using the last treatment CT images. RESULTS: Fifteen patients, 9 men
      and 6 women with a median age of 48 years, were identified in our database. All
      tumors were located in the lower extremity. During treatment, all tumors
      decreased in volume (P = .001). The median change in volume from CT simulation to
      the last image guided radiation therapy image set was -42% (-142 cm(3) median
      absolute reduction). Volume reduction ranged from -8% to -69%. The median rate of
      volume change was -5.5 cm(3)/day (range, -0.4 to -14.1). Five patients were
      clinically judged to require replanning during the course of treatment, all of
      them during the first 3 weeks. Shrinkage was typically greatest in the transverse
      direction. The dose distribution did not change significantly when the volumetric
      changes were taken into account, except for a higher maximal dose to adjacent
      bone. CONCLUSIONS: Our results confirm that MLS shrink significantly during
      radiation treatment. In spite of the large volumetric changes, we found little
      change in the dose to the tumor and surrounding structures. Routine treatment
      replanning may not be required in these patients but the interval from CT
      simulation to first treatment should be minimized to avoid the need for early
      replanning due to tumor progression.

PMID- 24674363
TI  - Prospective assessment of an atlas-based intervention combined with real-time
      software feedback in contouring lymph node levels and organs-at-risk in the head
      and neck: Quantitative assessment of conformance to expert delineation.
AB  - PURPOSE: A number of studies have previously assessed the role of teaching
      interventions to improve organ-at-risk (OAR) delineation. We present a
      preliminary study demonstrating the benefit of a combined atlas and real time
      software-based feedback intervention to aid in contouring of OARs in the head and
      neck. METHODS AND MATERIALS: The study consisted of a baseline evaluation, a real
      time feedback intervention, atlas presentation, and a follow-up evaluation. At
      baseline evaluation, 8 resident observers contoured 26 OARs on a computed
      tomography scan without intervention or aid. They then received feedback
      comparing their contours both statistically and graphically to a set of atlas
      based expert contours. Additionally, they received access to an atlas to contour
      these structures. The resident observers were then asked to contour the same 26
      OARs on a separate computed tomography scan with atlas access. In addition, 6
      experts (5 radiation oncologists specializing in the head and neck, and 1
      neuroradiologist) contoured the 26 OARs on both scans. A simultaneous truth and
      performance level estimation (STAPLE) composite of the expert contours was used
      as a gold-standard set for analysis of OAR contouring. RESULTS: Of the 8 resident
      observers who initially participated in the study, 7 completed both phases of the
      study. Dice similarity coefficients were calculated for each user-drawn structure
      relative to the expert STAPLE composite for each structure. Mean dice similarity
      coefficients across all structures increased between phase 1 and phase 2 for each
      resident observer, demonstrating a statistically significant improvement in
      overall OAR-contouring ability (P < .01). Additionally, intervention improved
      contouring in 16/26 delineated organs-at-risk across resident observers at a
      statistically significant level (P <= .05) including all otic structures and
      suprahyoid lymph node levels of the head and neck. CONCLUSIONS: Our data suggest
      that a combined atlas and real-time feedback-based educational intervention
      detectably improves contouring of OARs in the head and neck.

PMID- 24674364
TI  - Rotational setup errors in pediatric stereotactic radiation therapy.
AB  - PURPOSE: Stereotactic radiation therapy (SRT) is an increasingly commonly used
      technique in children. The use of image guidance increases the ability to
      accurately position patients. With our robotic couch, rotational errors that can
      be corrected are limited to approximately 3 degrees. Given this limitation, we
      reviewed the rotational setup errors in our pediatric brain tumor population.
      METHODS AND MATERIALS: We reviewed the rotational corrections for all pediatric
      (age <=21 years old) patients treated at our facility from 2009 to 2011. We
      compared children <5 years old treated to children between 5 and 21 years old
      (>=5 years old). Also, we analyzed the effect of steroid use and trends in
      rotational errors over the treatment period in each age group. RESULTS: The mean
      pitch, roll, and yaw rotational setup errors for younger children are -0.70 +/-
      2.60 degrees, -0.06 +/- 1.89 degrees, and 0.69 +/- 2.42 degrees, respectively;
      for children >=5 years old, they are 0.46 +/- 2.09 degrees, -0.06 +/- 1.89
      degrees, and 0.69 +/- 2.42 degrees, respectively. The mean pitch corrections are
      larger for children <5 years old (P < .001) and the variance of the pitch, roll,
      and yaw corrections are all larger for children <5 years old (P < .001). The
      frequency of rotational errors above 3 degrees for pitch, roll, and yaw is 21.7%,
      10.6%, and 20.9% for children <5 years old, and 15.6%, 2.1%, and 13.8% for
      children >=5 years old. In both age groups, pitch and roll corrections were
      larger for children treated with steroids. CONCLUSIONS: Rotational errors in our
      pediatric population occur more frequently than previously reported, and are more
      common in younger children and in children treated with steroids. These
      rotational set up errors may not be fully correctable due to mechanical and
      safety limitations. We have altered our planning and treatment process to better
      account for rotational errors in children receiving SRT.

PMID- 24674365
TI  - Surgical placement of biologic mesh spacers prior to external beam radiation for
      retroperitoneal and pelvic tumors.
AB  - PURPOSE: To determine the feasibility of surgical placement of biologic mesh
      spacers to displace bowel and other radiation-sensitive organs prior to external
      beam radiation for difficult retroperitoneal and pelvic tumors. METHODS AND
      MATERIALS: Tumors were resected if possible, and intraoperative electron
      radiation therapy (IOERT) was directed to the tumor or tumor bed in selected
      patients. Biologic mesh spacers comprised of cadaveric human skin treated to
      remove cells and preserve extracellular matrix (Alloderm; Lifecell, Branchburg,
      NJ) were then placed around the tumor or tumor bed. External radiation techniques
      included proton beam radiation therapy (PBRT) and intensity modulated radiation
      therapy (IMRT). RESULTS: Patients had primary sarcomas (n = 2), radiation
      associated sarcomas (n = 1), or isolated metastases (n = 2) in the
      retroperitoneum or pelvis. One patient received preoperative radiation. Three
      tumors were marginally resected (R1 resection) while 2 tumors were left in situ,
      and 3 patients received IOERT (10-17 Gy) to the tumor or tumor bed. Up to 4
      sheets of biologic mesh were used as spacers around the tumor or tumor bed to
      displace small bowel, colon, ureter, bladder, or pancreas. The average distance
      of the 4 closest organs prior to mesh placement was 1.3-9 mm and after mesh
      placement was 8.0-23.5 mm. Preoperative or postoperative radiation 36-76 Gy was
      delivered by IMRT or PBRT. There were no early complications from mesh placement
      and late complications possibly related to radiation included 1 vertebral body
      compression fracture and 1 deep vein thrombosis. There were no mesh-related
      infections and none of the meshes required removal. All 5 patients currently
      remain free of disease progression after 3-38 months. CONCLUSIONS: Biologic mesh
      spacers can be placed around tumors or tumor beds to displace radiation-sensitive
      organs and may allow for safer delivery of external beam radiation.

PMID- 24674366
TI  - Epidemiologic study of compliance to postmastectomy radiation therapy guidelines
      in breast cancer patients in China between 1999 and 2008.
AB  - PURPOSE: To evaluate compliance with postmastectomy radiation therapy (PMRT)
      guidelines in breast cancer patients in China over a 10-year period. METHODS AND
      MATERIALS: A hospital-based, nationwide, multicenter retrospective epidemiologic
      study of primary breast cancer in women was conducted. Seven first-class, upper
      level hospitals from different geographic regions of China were selected. One
      month was randomly selected to represent each year from 1999-2008 in every
      hospital. All inpatient cases within the selected months were reviewed and
      demographic, clinical, and pathologic characteristics and treatment patterns were
      collected. Patients enrolled in this study had to meet the following inclusion
      criteria: (1) treated with mastectomy and axillary dissection; (2) information
      regarding whether or not they received postmastectomy radiation therapy was
      available; and (3) information about staging was available. Patients were divided
      into 3 groups based on National Comprehensive Cancer Network guidelines.
      Utilization of PMRT in each group was analyzed and compared between different
      years and different hospitals. RESULTS: A total of 2310 patients were analyzed.
      There were 643 (27.8%) patients in the PMRT recommended group, 557 (24.1%)
      patients in the controversial group, and 1110 (48.1%) patients in the
      nonrecommended group. PMRT was used in 48.8% of patients in the recommended
      group, 15.6% in the controversial group, and 5.7% in the nonrecommended group.
      There was a trend toward increasing use of radiation therapy in the recommended
      and controversial groups from 1999-2008. The use of PMRT in the nonrecommended
      group remained relatively stable from 1999-2008. Fewer positive nodes and
      nonreceipt of chemotherapy or hormone therapy were associated with underuse of
      PMRT in the recommended group. In the controversial group, a higher ratio of
      positive nodes was associated with use of PMRT. CONCLUSIONS: There is an apparent
      underuse of PMRT in the PMRT recommended group. Efforts should be made to improve
      the compliance to PMRT guidelines.

PMID- 24674367
TI  - Changes in breast cancer risk associated with different volumes, doses, and
      techniques in female Hodgkin lymphoma patients treated with supra-diaphragmatic
      radiation therapy.
AB  - PURPOSE: The contribution of thoracic radiation in increasing secondary breast
      cancer (BC) risk in female Hodgkin lymphoma patients is well known, and recent
      changes in radiation therapy volumes, doses and techniques are supposed to
      minimize it. In this study, we compared different radiation therapy solutions in
      terms of secondary BC induction risk with the aim of selecting which could be
      considered the most protective. METHODS AND MATERIALS: In 10 female patients
      under 30 years old we estimated breast cancer risk for different combined
      treatment solutions (involved field vs involved nodal radiation therapy [IFRT vs
      INRT], 30 Gy vs 20 Gy, 3-dimensional conformal radiation therapy vs volumetric
      modulated arc therapy [3DCRT vs VMAT]). The organ equivalent dose (OED) method
      was used for dose calculation, as OED is directly related to the excess risk.
      Estimated OED mean values for all options in all patients were then analyzed and
      compared. RESULTS: INRT was significantly associated with a lower OED, regardless
      of total dose and technique (0.43 vs 1.15, P < .0001). The relative OED reduction
      from IFRT to INRT was approximately 60%. The dose of 20 Gy resulted in a
      significant reduction of OED, approximately 25% (0.68 vs 0.9, P < .01). VMAT did
      not show significantly higher OED when compared with 3DCRT (0.84 vs 0.74, P =
      .15). The combination of INRT and 20 Gy lead to a decrease in OED of
      approximately 70% if compared with IFRT 30 Gy. CONCLUSIONS: The INRT approach
      substantially reduces OED, independent of dose and technique; the dose reduction
      from 30 Gy to 20 Gy also has a significant impact, and as expected INRT-20 Gy
      resulted to be the solution at lowest risk. No differences were observed when
      comparing different techniques (3DCRT vs VMAT). The combination of these
      innovative approaches might lead to a substantial reduction in secondary breast
      cancer risk in this patient population.

PMID- 24674368
TI  - Radiation therapy for optic nerve sheath meningioma.
AB  - PURPOSE: To explain the concepts that radiation oncologists should understand to
      manage patients with optic nerve sheath meningioma (ONSM). To accomplish this
      goal we first describe our institution's experience with the treatment of ONSM
      with radiation therapy and then use this data set as a framework for explaining
      the role of radiation therapy in the treatment of this uncommon tumor. METHODS
      AND MATERIALS: We studied the outcomes of all 15 patients treated at our medical
      center with radiation therapy for ONSM between 1990 and 2006. The minimum follow
      up was 5 years (median, 12 years). The median dose was 50.4 Gy at 1.8 Gy per
      treatment (range, 50-54 Gy). RESULTS: No patient experienced tumor progression.
      The rates of local control, regional control, and relapse free-survival were all
      100%. Radiographic tumor response after radiation therapy was as follows: No
      change in 93%; and a reduction in size in 7%. Vision status after radiation
      therapy was as follows: Stable in 60%; improved in 27%; and decreased in 13%.
      Vision was classified as "useful" at last follow-up in 86% of patients with
      useful vision at the time of radiation therapy. The only treatment complication
      was moderate retinopathy in 2 patients. At last follow-up, no patient had
      developed a second tumor. CONCLUSIONS: Radiation therapy with 50.4 Gy at 1.8 Gy
      per treatment prevents tumor growth and vision deterioration in most patients
      with ONSM.

PMID- 24674370
TI  - Radiation therapy for clinically node-positive prostate adenocarcinoma is
      correlated with improved overall and prostate cancer-specific survival.
AB  - PURPOSE: To evaluate the effect of radiation therapy on prostate cancer-specific
      and overall survival with node-positive cancer in a retrospective Surveillance,
      Epidemiology and End RESULTS (SEER) population based study. METHODS AND
      MATERIALS: The survival of subjects with cT1-T4,cN1,M0 prostate adenocarcinoma
      diagnosed between 1988 and 2006 were compared with univariate and multivariate
      Cox regression analysis. RESULTS: A total of 1100 subjects, with a median age of
      69 years and median follow-up time of 90 months, were identified. The 10-year
      cancer-specific survival for men who had no definitive therapy was 50.3% and for
      those who had radiation therapy 62.7%. This was significantly different favoring
      radiation therapy (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.54
      to 0.82, P <= .01). On multivariate analysis evaluating age, histologic grade, T
      stage, year of diagnosis, marital status, SEER registry and radiation therapy,
      radiation therapy (HR = 0.67, 95% CI = 0.54 to 0.84, P <= .01), year of diagnosis
      (HR = 0.96, 95% CI = 0.93 to 0.99, P = .01), and low and intermediate grade
      disease were correlated with improved CSS. The number needed to treat to prevent
      1 prostate cancer-specific death at 10 years was 8 persons. A cause of death
      analysis revealed non-prostate cancer deaths were not statistically different in
      the comparison groups. CONCLUSIONS: Radiation therapy is correlated with a
      clinically significant reduction in all cause and prostate cancer-specific death.

PMID- 24674369
TI  - Effect of prophylactic fluconazole on oral mucositis and candidiasis during
      radiation therapy for head-and-neck cancer.
AB  - PURPOSE: Radiation therapy (RT) or chemoradiation therapy (CRT) for carcinoma of
      the head and neck can result in high rates of candidiasis and mucositis.
      Prophylactic fluconazole (FCZ) has been shown to reduce the incidence of
      candidiasis. We report our outcomes of patients with head-and-neck cancer
      undergoing CRT treated prophylactically with FCZ. METHODS AND MATERIALS: An
      institutional review board-approved database of head-and-neck cancer patients
      treated with RT or CRT was reviewed to identify patients treated between 2004 and
      2009 who received at least 50 Gy to approximately two-thirds of the oral cavity
      or oropharynx mucosa. Eligible patients were divided into 2 groups: the usual
      care group and the prophylaxis group. The primary endpoints were the incidence of
      mucositis and candidiasis. RESULTS: A total of 181 patients were eligible for
      analysis: 72 patients in the prophylactic group and 109 patients in the usual
      care group. Patient characteristics and radiation dose were comparable between
      groups. RT alone was given in 28 patients (16%). Mucositis data were available in
      161 (89%) patients. Grade 2 or higher mucositis was seen in 131 (81%) patients.
      Prophylactic FCZ had significantly decreased grade 2 or higher mucositis. In the
      usual care group and prophylaxis group patients, 83 of 93 patients (89.3%) and 48
      of 68 patients (70.6%), respectively, developed grade 2 or higher mucositis (P =
      .003). CONCLUSIONS: Prophylactic administration of FCZ twice weekly during CRT
      for head-and-neck cancer reduces incidence of mucositis and thrush.

PMID- 24674371
TI  - Use of postexcision preirradiation mammography in patients with ductal carcinoma
      in situ of the breast treated with breast-conserving therapy.
AB  - PURPOSE: Postexcision preirradiation mammography (PPM) is frequently performed in
      patients with ductal carcinoma in situ (DCIS) treated with breast-conserving
      therapy (BCT) to evaluate for residual suspicious calcifications; but no clear
      evidence supports this practice. The current study was undertaken to investigate
      the value of PPM in the management of patients with DCIS. METHODS AND MATERIALS:
      We conducted a retrospective review of patients treated for DCIS with BCT at the
      University of Pennsylvania. The impact of PPM on surgical management and on local
      recurrence was evaluated. Factors associated with the use of PPM, the results of
      PPM, and the likelihood of finding residual malignancy at the time of re-excision
      in patients with PPM were also examined. RESULTS: One hundred forty-four of 281
      patients (51%) underwent PPM. Of the 144 patients who received PPM, 34 (24%; 95%
      confidence interval, 17%-31%) had residual suspicious calcifications (a "positive
      PPM"). Of the 34 patients with a positive PPM, all underwent a re-excision and 19
      (56%; 95% confidence interval, 35%-70%) were found to have residual malignancy.
      Ten of 34 patients with a positive PPM had negative margins, of which 6 had a
      residual malignancy. Assuming all patients with close, positive, or indeterminate
      surgical margins would have undergone re-excision regardless of the findings of
      PPM, PPM resulted in a change in surgical management in 7% (10/144) of patients
      and removal of residual DCIS in 4% (6/144). With a median follow-up of 9.5 years,
      the use of PPM was not associated with an improvement in 10-year local recurrence
      free survival (94.8% vs 91.5%, P = .368). CONCLUSIONS: In this study, PPM
      affected surgical management in only a small percentage of patients and had no
      impact on local recurrence. The routine use of PPM in women undergoing BCT for
      DCIS may not be warranted.

PMID- 24674372
TI  - Patterns of local failure for sinonasal malignancies.
AB  - PURPOSE: To identify the patterns of local failure for sinonasal malignancies
      treated with radiation therapy (RT). METHODS AND MATERIALS: We retrospectively
      identified 79 patients with sinonasal malignancies treated between 2000 and 2011.
      The median follow-up was 34 months (7-137). Fifty patients (63%) had surgery and
      RT with or without chemotherapy, and 29 (37%) received definitive chemoradiation
      therapy. Twenty-six of 79 patients (33%) failed locally; 11 had persistent
      disease and 15 had local recurrence (LR). The patients with LR had at least a 3
      month disease-free interval posttreatment. Imaging of the 15 LR was registered to
      the treatment planning computed tomography. Failures were categorized as in
      field, marginal, or out-of-field if >95%, 20%-95%, or <20% of the LR was within
      the 95% prescription isodose line, respectively. RESULTS: Of the 15 patients with
      LR, 7 were in-field, 2 were marginal, and 6 were out-of-field. For 3 patients,
      treatment plans were not retrievable; however, it was apparent from clinical
      records that 2 had in-field LR and 1 had an out-of-field LR (untreated
      contralateral maxillary sinus). No patient with a marginal or out-of-field
      recurrence had more than 39% of their recurrent tumor volume within 95% of the
      prescribed dose. Coverage of the LR by 54 Gy and 45 Gy was suboptimal in 7/7 and
      5/7 patients with LR, respectively. Marginal and out-of-field LR were
      predominantly above the pretreatment tumor location and at the level of or
      superior to the eyes. CONCLUSIONS: Sinonasal malignancies failed marginally or
      out-of-field in 53% (8/15) of LR and 31% (8/26) of all local failures. The
      anatomic location of these marginal and out-of field LR are predominately at, or
      superior to, the level of the eyes. This pattern of failure may be directly
      related to efforts to minimize RT to the optic structures and the degree of
      difficulty of skull base operations.

PMID- 24674373
TI  - Utilization of preoperative radiation therapy in the management of rectal cancer:
      A population-based analysis.
AB  - PURPOSE: Preoperative radiation therapy (RT) improves local control in resectable
      rectal cancer compared with postoperative RT or surgery alone. Although clinical
      practice guidelines exist, adherence to recommendations for preoperative RT is
      unclear. This population-based study examines preoperative RT utilization rates
      for rectal cancer patients in a Canadian province and investigates factors
      influencing its usage. METHODS AND MATERIALS: Between 2004 and 2009, all stage II
      and III rectal cancer patients treated with definitive surgery were identified
      using the Manitoba Cancer Registry. Patients not receiving resection of the
      primary tumor, as determined by administrative procedure codes, were excluded.
      Factors potentially influencing preoperative RT utilization, including age,
      gender, stage, year of diagnosis, and geographic distance from RT facility, were
      analyzed using logistic regression analyses. Overall survival outcomes were also
      examined. RESULTS: The registry identified 776 patients meeting the study
      inclusion criteria. Preoperative RT utilization increased from 3% in 2004 to 41%
      in 2009. Postoperative RT utilization decreased from 48% to 17% during the same
      period. Rates of surgery alone remained stable at 40%-50%. Factors influencing
      preoperative RT utilization were younger age (P < .0001), stage III disease (P =
      .02), and later year of diagnosis (P < .0001). Elderly patients age 70 years and
      over were predominantly treated with surgery alone. Actuarial 5-year overall
      survival for patients receiving preoperative RT postoperative RT, and surgery
      alone were 80%, 73%, and 58%, respectively. CONCLUSIONS: Steadily increasing
      utilization of preoperative compared with postoperative RT is evident; however,
      rates of surgery alone remained unchanged. Strategies to improve preoperative RT
      utilization, particularly among elderly patients, are needed.

PMID- 24674374
TI  - Clinical and molecular exploration of the impact of radiation therapy on Marfan
      syndrome patients.

PMID- 24674375
TI  - Less intense therapy for human papilloma virus associated oropharyngeal
      carcinoma: Throwing caution to the wind? In Regard to Patel et al.

PMID- 24674376
TI  - In Reply to Revannasiddaiah et al: "Less intense therapy for human papilloma
      virus associated oropharyngeal carcinoma: Throwing caution to the wind?".

PMID- 24674377
TI  - How important is dosimetrist experience for intensity modulated radiation
      therapy? A comparative analysis of a head and neck case.
AB  - PURPOSE: Treatment planning for IMRT is a complex process that requires
      additional training and expertise. The aim of this study was to compare and
      analyze IMRT plans generated by dosimetrists with varying levels of IMRT planning
      experience. METHODS AND MATERIALS: The computed tomography (CT) data of a patient
      previously treated with IMRT for left tonsillar carcinoma were used. The
      patient's preexisting planning target volumes (PTVs) and all organs at risk were
      provided with the CT data set. Six dosimetrists with variable IMRT planning
      experience generated IMRT plans according to the department's protocol. Plan
      analysis included visual inspection and comparison of dose-volume histogram,
      conformity indices, treatment delivery efficiency, and dose delivery accuracy.
      RESULTS: Visual review of the dose distribution showed that the 6 plans were
      comparable. However, only the 2 most experienced dosimetrists were able to meet
      the strict PTV aims and critical structure constraints. The least experienced
      dosimetrist had the worst planning outcome. Comparison of delivery efficiency
      showed that the number of segments, total monitor units, and treatment time
      increased as the IMRT planning experience decreased. CONCLUSIONS: Dosimetrists
      with higher levels of IMRT planning experience produced a better quality head and
      neck IMRT plan. Different planning experience may need to be considered when
      organizing appropriate departmental resources.

PMID- 24674378
TI  - Care demands on mothers caring for a child with Down syndrome: Malaysian
      (Sarawak) mothers' perspectives.
AB  - This paper examines the experiences of mothers caring for a child with Down
      syndrome in the Malaysian (Sarawak) context. Qualitative interviews were
      conducted with 26 biological mothers of children with Down syndrome aged 18 years
      and below. They were accessed through selected child health clinics, community
      based rehabilitation centres and schools using purposive sampling within two
      regions in Sarawak, one of the two Borneo States of Malaysia. Major themes
      emerging within the context of care demands were children's health, developmental
      delays, daily needs and behaviour issues. The insights obtained into the care
      demands experienced by mothers of children with Down syndrome have several
      implications for practice by care professionals. 

PMID- 24674379
TI  - Identification of heat shock factor binding protein in Plasmodium falciparum.
AB  - BACKGROUND: Heat shock factor binding protein (HSBP) was originally discovered in
      a yeast two-hybrid screen as an interacting partner of heat shock factor (HSF).
      It appears to be conserved in all eukaryotes studied so far, with yeast being the
      only exception. Cell biological analysis of HSBP in mammals suggests its role as
      a negative regulator of heat shock response as it appears to interact with HSF
      only during the recovery phase following exposure to heat stress. While the
      identification of HSF in the malaria parasite is still eluding biologists, this
      study for the first time, reports the presence of a homologue of HSBP in
      Plasmodium falciparum. METHODS: PfHSBP was cloned and purified as his-tag fusion
      protein. CD (Circular dichroism) spectroscopy was performed to predict the
      secondary structure. Immunoblots and immunofluorescence approaches were used to
      study expression and localization of HSBP in P. falciparum. Cellular
      fractionation was performed to examine subcellular distribution of PfHSBP.
      Immunoprecipitation was carried out to identify HSBP interacting partner in P.
      falciparum. RESULTS: PfHSBP is a conserved protein with a high helical content
      and has a propensity to form homo-oligomers. PfHSBP was cloned, expressed and
      purified. The in vivo protein expression profile shows maximal expression in
      trophozoites. The protein was found to exist in oligomeric form as trimer and
      hexamer. PfHSBP is predominantly localized in the parasite cytosol, however, upon
      heat shock, it translocates to the nucleus. This study also reports the
      interaction of PfHSBP with PfHSP70-1 in the cytoplasm of the parasite.
      CONCLUSIONS: This study emphasizes the structural and biochemical conservation of
      PfHSBP with its mammalian counterpart and highlights its potential role in
      regulation of heat shock response in the malaria parasite. Analysis of HSBP may
      be an important step towards identification of the transcription factor
      regulating the heat shock response in P. falciparum.

PMID- 24674380
TI  - Thyroidal abscesses in third and fourth branchial anomalies: not only a
      paediatric diagnosis.
AB  - INTRODUCTION: Acute suppurative thyroiditis and recurrent abscess formation due
      to third and fourth branchial anomalies typically present in children. However,
      thyroid abscesses in branchial anomalies may occur in adulthood as well. Failure
      to recognize and delayed drainage of a neck abscess may lead to a fulminant life
      threatening outcome. METHODS: This is a retrospective case series. The study
      group comprised all patients presenting over a 12-month period from January to
      December 2012 with thyroid abscesses and a branchial cleft anomaly in two
      centres, one adult and the other paediatric. Patient demographics, clinical
      presentation, imaging, surgical management, definitive histology and outcomes
      were documented. RESULTS: Five patients were identified with a history of thyroid
      abscesses. Only one was a child (aged 9 years) with the other four being adults
      (aged 20, 34, 37 and 41 years). All patients had third or fourth left branchial
      cleft anomalies, presenting as suppurative thyroiditis with a left-sided thyroid
      abscess. Management options ranged from abscess drainage on initial presentation,
      primary thyroid lobectomy or delayed thyroid lobectomy following abscess
      drainage. CONCLUSION: Acute suppurative thyroidits and thyroid abscesses is not
      just a paediatric diagnosis but may present at any age. In both children and
      adults, a thyroid abscess almost always arises from branchial cleft anomalies.

PMID- 24674381
TI  - NPAS3 variants in schizophrenia: a neuroimaging study.
AB  - BACKGROUND: This research is a one-site neuroimaging component of a two-site
      genetic study involving patients with schizophrenia at early and later stages of
      illness. Studies support a role for the neuronal Per-Arnt-Sim 3 (NPAS3) gene in
      processes that are essential for normal brain development. Specific NPAS3
      variants have been observed at an increased frequency in schizophrenia. In
      humans, NPAS3 protein was detected in the hippocampus from the first trimester of
      gestation. In addition, NPAS3 protein levels were reduced in the dorsolateral
      prefrontal cortex of some patients with schizophrenia. Npas3 knockout mice
      display behavioural, neuroanatomical and structural changes with associated
      severe reductions in neural precursor cell proliferation in the hippocampal
      dentate gyrus. This study will evaluate the hypothesis that the severe reductions
      in neural precursor cell proliferation in the dentate gyrus will be present to
      some degree in patients carrying schizophrenia-associated NPAS3 variants and less
      so in other patients. METHODS/DESIGN: Patients enrolled in the larger genetic
      study (n = 150) will be invited to participate in this neuroimaging arm. The
      genetic data will be used to ensure a sample size of 45 participants in each
      genetic subgroup of patients (with and without NPAS3 variants). In addition, we
      will recruit 60 healthy controls for acquisition of normative data. The following
      neuroimaging measures will be acquired from the medial temporal region: a) an
      index of the microcellular environment; b) a macro-structural volumetric measure
      of the hippocampus; and c) concentration levels of N-acetylaspartate, a marker of
      neuronal health. DISCUSSION: This study will help to establish the contribution
      of the NPAS3 gene and its variants to brain tissue abnormalities in
      schizophrenia. Given the genetic and phenotypic heterogeneity of the disorder and
      the large variation in outcomes, the identification of biological subgroups may
      in future support tailoring of treatment approaches in order to optimize
      recovery.

PMID- 24674382
TI  - Peripheral antinociception and anti-inflammatory effects of sulphated
      polysaccharides from the alga Caulerpa mexicana.
AB  - Sulphated polysaccharides from marine algae are widely used in biotechnological
      and pharmaceutical areas. In this study, we evaluated the effects of sulphated
      polysaccharides from the green marine alga Caulerpa mexicana (Cm-SPs) in
      nociceptive and inflammatory models in rodents. Cm-SPs (10 or 20 mg/kg),
      administered i.v. in Swiss mice, significantly reduced nociceptive responses, as
      measured by the number of writhes in response to acetic acid. Cm-SPs (10 or 20
      mg/kg) also reduced second-phase responses in the formalin test, but did not
      exhibit a significant antinociceptive effect in the hot plate test, suggesting
      that its antinociceptive action occurs through a peripheral mechanism. Cm-SPs (5,
      10 or 20 mg/kg), administered s.c. in wistar rats 1 hr before carrageenan,
      dextran, histamine or serotonin, were tested in paw oedema models. Cm-SPs (10 or
      20 mg/kg) reduced carrageenan-induced paw oedema and myeloperoxidase activity in
      the paw. In addition, Cm-SPs (20 mg/kg) inhibited dextran- or histamine-induced
      paw oedema, but not serotonin-induced oedema, suggesting that histamine is the
      major target of Cm-SPs anti-oedematogenic activity. Finally, Cm-SPs (20 mg/kg)
      administered in mice did not show significant signs of toxicity. In conclusion,
      Cm-SPs appear to be promising natural modulatory agents for pain and inflammatory
      conditions.

PMID- 24674384
TI  - Effect of calcium carbonate combined with calcitonin on hypercalcemia in
      hemodialysis patients.
AB  - This short-term study assessed the efficacy and safety of calcium carbonate
      combined with calcitonin in the treatment of hypercalcemia in hemodialysis
      patients. Patients (n=64) on hemodialysis for chronic kidney disease for more
      than 6 months were included based on total serum calcium more than 10.5 mg/dL.
      All patients were randomized (1:1) to receive calcium carbonate combined with
      calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels
      of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every
      month, bone mass density (BMD) and coronary artery calcium scores (CACS) were
      measured at 3 months. During the study period, serum calcium decreased from 10.72
      +/- 0.39 to 10.09 +/- 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79
      +/- 1.05 to 5.46 +/- 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I
      and Group II were not significantly different from the baseline. There were no
      significant differences in CACS in either group. There were no significant
      differences in the BMD values between Group I and baseline. In Group II, the BMD
      values at the lumbar spine and femoral neck were significantly lower than those
      before the trial and significantly lower than the corresponding values of Group I
      (P<0.05). Calcium carbonate combined with calcitonin and lanthanum carbonate were
      equally effective in the suppression of hypercalcemia in hemodialysis patients.
      There were no serious treatment-related adverse events in treatment with calcium
      carbonate combined with calcitonin.

PMID- 24674383
TI  - Assessment of global myocardial perfusion reserve using cardiovascular magnetic
      resonance of coronary sinus flow at 3 Tesla.
AB  - BACKGROUND: Despite increasing clinical use, there is limited data regarding
      regadenoson in stress perfusion cardiovascular magnetic resonance (CMR). In
      particular, given its long half-life the optimal stress protocol remains unclear.
      Although Myocardial Perfusion Reserve (MPR) may provide additive prognostic
      information, current techniques for its measurement are cumbersome and
      challenging for routine clinical practice.The aims of this study were: 1) To
      determine the feasibility of MPR quantification during regadenoson stress CMR by
      measurement of Coronary Sinus (CS) flow; and 2) to investigate the role of
      aminophylline reversal during regadenoson stress-CMR. METHODS: 117 consecutive
      patients with possible myocardial ischemia were prospectively enrolled. Perfusion
      imaging was performed at 1 minute and 15 minutes after administration of 0.4 mg
      regadenoson. A subgroup of 41 patients was given aminophylline (100 mg) after
      stress images were acquired. CS flow was measured using phase-contrast imaging at
      baseline (pre CS flow), and immediately after the stress (peak CS flow) and rest
      (post CS flow) perfusion images. RESULTS: CS flow measurements were obtained in
      92% of patients with no adverse events. MPR was significantly underestimated when
      calculated as peak CS flow/post CS flow as compared to peak CS flow/pre CS flow
      (2.43+/-0.20 vs. 3.28+/-0.32, p=0.03). This difference was abolished when
      aminophylline was administered (3.35+/-0.44 vs. 3.30+/-0.52, p=0.95). Impaired
      MPR (peak CS flow/pre CS flow<2) was associated with advanced age, diabetes,
      current smoking and higher Framingham risk score. CONCLUSIONS: Regadenoson stress
      CMR with MPR measurement from CS flow can be successfully performed in most
      patients. This measurement of MPR appears practical to perform in the clinical
      setting. Residual hyperemia is still present even 15 minutes after regadenoson
      administration, at the time of resting-perfusion acquisition, and is completely
      reversed by aminophylline. Our findings suggest routine aminophylline
      administration may be required when performing stress CMR with regadenoson.

PMID- 24674385
TI  - Corneal sensitivity in healthy bovine calves.
AB  - OBJECTIVE: To evaluate corneal sensitivity as measured by the corneal touch
      threshold in healthy bovine calves. ANIMALS STUDIED: Twelve clinically normal
      male calves with predominantly Holstein genetics and a median age of 76.5 days
      (range, 67-92 days). PROCEDURES: Corneal touch threshold (CTT) of the central
      cornea was measured in both eyes of each calf using a Cochet-Bonnet
      aesthesiometer. RESULTS: The mean +/- standard deviation corneal touch threshold
      of all eyes was 1.33 +/- 1.1 g/mm(2) (range, 0.62-66.15 g/mm(2) ), corresponding
      to a filament length of 34.56 +/- 8.02 mm (range, 14-47.5 mm). There was no
      significant difference between fellow eyes. CONCLUSIONS: Cochet-Bonnet
      aesthesiometry was well tolerated in all 12 calves using a modified head
      restraint. Calves in this study may have a relatively sensitive central cornea
      compared to adult cattle and some other species; however, wide variation among
      individuals and eyes may be possible. Studies utilizing larger calf populations
      are necessary to establish reference ranges.

PMID- 24674386
TI  - Rapid purification of gram quantities of beta-sitosterol from a commercial
      phytosterol mixture.
AB  - BACKGROUND: beta-Sitosterol, a plant sterol or phytosterol, has commercial uses
      in the nutraceutical and pharmaceutical industries, but is also employed
      frequently in biological research. Phytosterols always accumulate as mixtures,
      and obtaining highly pure beta-sitosterol in larger quantities for biological
      assays has been a challenge. FINDINGS: An improved method for the rapid
      purification of beta-sitosterol from a commercial phytosterol extract is
      presented. Fractional crystallization of soybean oil yielded a soluble and an
      insoluble fraction. beta-Sitosterol was purified by silica gel and Na-Y zeolite
      chromatography. CONCLUSION: The rapid and cost effective three-step purification
      described here afforded beta-sitosterol in gram quantities with high purity
      (>92%) and yield (>22%).

PMID- 24674387
TI  - A neonatal case of chronic granulomatous disease, initially presented with
      invasive pulmonary aspergillosis.
AB  - Chronic granulomatous disease (CGD) often presents with infectious illness, such
      as repeating bacterial and fungal infections, due to the inability to generate
      superoxide, which would destroy certain infectious pathogens, and is usually
      diagnosed in childhood. We describe a CGD case diagnosed in neonatal period, who
      initially presented with invasive aspergillosis. Neonatal invasive pulmonary
      aspergillosis is very rare and, to the best of our knowledge, this might be the
      youngest case in Japan. 

PMID- 24674388
TI  - An evaluation of multiple phenotypic screening methods for Klebsiella pneumoniae
      carbapenemase (KPC)-producing Enterobacteriaceae.
AB  - Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae may
      display MICs to carbapenems within susceptible or intermediate ranges, prompting
      confirmatory testing. Four phenotypic methods to detect KPC producers were
      evaluated against a collection of clinical Enterobacteriaceae isolates. Meropenem
      phenylboronic acid double disk synergy testing demonstrated the best performance
      with 100% sensitivity and specificity. 

PMID- 24674389
TI  - Telocytes in human heart valves.
AB  - Valve interstitial cells (VICs) are responsible for maintaining the structural
      integrity and dynamic behaviour of the valve. Telocytes (TCs), a peculiar type of
      interstitial cells, have been recently identified by Popescu's group in
      epicardium, myocardium and endocardium (visit www.telocytes.com). The presence of
      TCs has been identified in atria, ventricles and many other tissues and organ,
      but not yet in heart valves. We used transmission electron microscopy and
      immunofluorescence methods (double labelling for CD34 and c-kit, or vimentin, or
      PDGF Receptor-beta) to provide evidence for the existence of TCs in human heart
      valves, including mitral valve, tricuspid valve and aortic valve. TCs are found
      in both apex and base of heart valves, with a similar density of 27-28
      cells/mm(2) in mitral valve, tricuspid valve and aortic valve. Since TCs are
      known for the participation in regeneration or repair biological processes, it
      remains to be determined how TCs contributes to the valve attempts to re
      establish normal structure and function following injury, especially a complex
      junction was found between TCs and a putative stem (progenitor) cell. 

PMID- 24674390
TI  - Recovery trends of Scrobicularia plana populations after restoration measures,
      affected by extreme climate events.
AB  - The Mondego estuary (Portugal) went through different ecological scenarios over
      the last decades. An eutrophication process led to a decline in the ecosystem
      quality. The ensuing restoration plan resulted into a gradual ecological
      recovery, which was impaired by the occurrence of successive extreme climate
      events that affected dynamics and productivity of key species. In this study we
      assess the response of the bivalve Scrobicularia plana to the impacts of these
      events in a recovery scenario, by comparing populations in two different
      intertidal habitats: a seagrass bed and a sandflat area. As a general tendency,
      S. plana, which was negatively affected by eutrophication, responded positively
      to restoration. However, the occurrence of extreme climate events seemed to
      affect recruitment success, biomass and production, impairing the recovery
      process. In the seagrass bed, S. plana maintained a stable and structured
      population, while in the sandflat area recovery clearly reverted into a decline,
      mainly concerning biomass and production values. This sequence of multiple
      stressors might have reduced S. plana resilience to further impacts and
      therefore, understanding the behavior of biological populations following
      restoration initiatives requires acknowledgement that some changes may not be
      easily reversible. 

PMID- 24674391
TI  - Effects of common seagrass restoration methods on ecosystem structure in
      subtropical seagrass meadows.
AB  - Seagrass meadows near population centers are subject to frequent disturbance from
      vessel groundings. Common seagrass restoration methods include filling
      excavations and applying fertilizer to encourage seagrass recruitment. We sampled
      macrophytes, soil structure, and macroinvertebrate infauna at unrestored and
      recently restored vessel grounding disturbances to evaluate the effects of these
      restoration methods on seagrass ecosystem structure. After a year of observations
      comparing filled sites to both undisturbed reference and unrestored disturbed
      sites, filled sites had low organic matter content, nutrient pools, and primary
      producer abundance. Adding a nutrient source increased porewater nutrient pools
      at disturbed sites and in undisturbed meadows, but not at filled sites.
      Environmental predictors of infaunal community structure across treatments
      included soil texture and nutrient pools. At the one year time scale, the
      restoration methods studied did not result in convergence between restored and
      unrestored sites. Particularly in filled sites, soil conditions may combine to
      constrain rapid development of the seagrass community and associated infauna. Our
      study is important for understanding early recovery trajectories following
      restoration using these methods. 

PMID- 24674392
TI  - Periostin accelerates human malignant melanoma progression by modifying the
      melanoma microenvironment.
AB  - Given no reliable therapy for advanced malignant melanoma, it is important to
      elucidate the molecular mechanisms underlying the disease progression. Using a
      quantitative proteomics approach, the 'isobaric tags for relative and absolute
      quantitation (iTRAQ)' method, we identified that the extracellular matrix
      protein, periostin (POSTN), was highly expressed in invasive melanoma compared
      with normal skin. An immunohistochemical analysis showed that POSTN was expressed
      in all invasive melanoma (n = 20) and metastatic lymph node (n = 5) tissue
      samples, notably restricted in their stroma. In terms of the intercellular
      regulation of POSTN, we found that there was upregulation of POSTN when melanoma
      cells and normal human dermal fibroblasts (NHDFs) were cocultured, with
      restricted expression of TGF-beta1 and TGF-beta3. In a functional analyses,
      recombinant and NHDF-derived POSTN significantly accelerated melanoma cell
      proliferation via the integrin/mitogen-activated protein kinase (MAPK) signaling
      pathway in vitro. The size of implanted melanoma tumors was significantly
      suppressed in POSTN/Rag2 double knockout mice compared with Rag2 knock-out mice.
      These results indicate that NHDF-derived POSTN accelerates melanoma progression
      and might be a promising therapeutic target for malignant melanoma.

PMID- 24674393
TI  - Treatment planning technique in patients receiving postmastectomy radiation
      therapy.
AB  - Many of the technical subtleties involved in postmastectomy radiation treatment
      planning will never be addressed in a robust clinical trial setting. However,
      these issues are faced daily by practicing radiation oncologists with little to
      guide them in the published literature. The purpose of this study was to survey a
      small number of breast care providers in both academic and private practice
      settings on practical aspects of postmastectomy radiation treatment planning.
      Topics addressed included the use of sophisticated dose-modulation algorithms,
      hypofractionation, bolus material, and dose-volume histogram (DVH) constraints.
      Fifty-two people responded to the survey, 50% in academics and 50% in private
      practice. As expected, wide variation in clinical practice was seen although a
      few general trends emerged. We include here, with the survey results, a review of
      the relevant literature for a number of different treatment-related issues.
      Although the use of postmastectomy radiation therapy is common, literature
      guiding the reader on technical aspects of delivery is sparse. The data presented
      here provide a general framework of what is considered acceptable by currently
      practicing radiation oncologists in many different practice settings. 

PMID- 24674394
TI  - Role of image guided radiation therapy in obese patients with gynecologic
      malignancies.
AB  - PURPOSE: We investigated the effect of body mass index on setup errors by
      analyzing daily shifts required in treating patients undergoing image guided
      radiation therapy (IGRT) for gynecologic malignancies. METHODS AND MATERIALS:
      Forty successive patients treated with daily kV-based IGRT for gynecologic
      malignancies between April 2009 and June 2012 were identified. Directional setup
      corrections were analyzed according to patient body mass index. Random and
      systematic setup errors were calculated. Image acquisition dose was estimated by
      performing ionization chamber measurements in a phantom. RESULTS: Obese patients
      had larger random setup errors, particularly in the right-left (R-L) direction,
      with a setup error of 7.6 mm, versus 3.9 mm for nonobese patients. The range of
      individual patient random errors in the R-L direction was 1.5 to 7.6 mm among
      nonobese patients versus 2.0 to 17.0 mm among obese patients (P = .03, F-test).
      For obese patients, daily IGRT prevented treating outside the planning target
      volume in 33% of fractions, versus 16% in the nonobese group (P = .001). The mean
      total image acquisition dose from daily kV-IGRT was approximately 3 cGy, versus
      150 cGy if daily megavoltage portal imaging were used to correct for erratic
      setup errors. CONCLUSIONS: Daily kV-based IGRT in obese patients allows for
      correction of erratic setup error and minimizes excess dose from portal imaging.

PMID- 24674395
TI  - Dosimetric and cost comparison of first fraction imaging versus fractional re
      imaging on critical organ dose in vaginal cuff brachytherapy.
AB  - PURPOSE: Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of
      the most common procedures performed in the treatment of early-stage endometrial
      cancer. However, current recommendations by the American Brachytherapy Society
      regarding fractional re-imaging and dose calculation for organs at risk for HDR
      vaginal cuff brachytherapy are not well defined. In this study, we aim to compare
      a fractional re-imaging approach using computed tomographic (CT) scans prior to
      each fraction with a first fraction imaging-only approach with respect to
      bladder, rectal, and bowel dosimetry. METHODS AND MATERIALS: Nineteen endometrial
      cancer patients undergoing vaginal cuff brachytherapy for endometrial cancer were
      imaged with CT scanning prior to every HDR fraction (fractional re-imaging
      [FRI]). Dose to the bowel, bladder, and rectum were calculated and compared with
      the estimated dose if imaging and planning were done only on the first fraction
      (first fraction imaging [FFI]). RESULTS: In the analysis of FFI versus FRI, we
      observed mean bladder doses of 8.34 Gy vs 8.33 Gy (P = .98), mean rectal doses of
      12.19 Gy versus 12.14 Gy (P = .81), and mean bowel doses of 2.82 Gy versus 2.76
      Gy (P = .81). The FFI approach underestimated the FRI doses to the bladder,
      rectum, and bowel by 20% or more in 11%, 5%, and 29% of patients, respectively.
      Cost analysis revealed an estimated $663.06, or a 35% savings per patient treated
      with FFI. CONCLUSIONS: There is no statistically significant difference in the
      mean dose to the bladder, rectum, or bowel in patients undergoing HDR vaginal
      cuff brachytherapy with a first fraction imaging scheme versus a fractional re
      imaging scheme. These results indicate that fractional re-imaging is not
      necessary except in patients whose estimated dose to critical organs is near the
      maximum limit.

PMID- 24674396
TI  - Evaluation of a balloon-based vaginal packing system and patient-controlled
      analgesia for patients with cervical cancer undergoing high-dose-rate
      intracavitary brachytherapy.
AB  - PURPOSE: To evaluate the following: (1) the dosimetric impact on the bladder and
      rectum due to a methodologic shift from general anesthesia (GA) to patient
      controlled analgesia (PCA), and from vaginal gauze packing (VGP) to vaginal
      balloon-based packing (VBP) for high-dose-rate (HDR) intracavitary brachytherapy;
      and (2) the tolerability of PCA versus GA. METHODS AND MATERIALS: Seventeen
      consecutively treated patients with cervical carcinoma who underwent tandem and
      ovoid (T&O) HDR brachytherapy from January 2009 to August 2010 were selected and
      reviewed. There were a total of 73 applications. Patients were packed either
      conventionally with VGP (n = 49) or with VBP (n = 24). Because different sedation
      methods can influence rectal and bladder dosimetric parameters all applications
      were grouped by packing method (VBP or VGP) as well as sedation method (GA or
      PCA). The International Commission on Radiation Units and Measurements (ICRU) and
      D2cc rectal and bladder doses were obtained from the treatment records and dose
      volume histograms, and respective percentage of prescription dose noted and
      compared. For patients receiving PCA, pain score on a scale of 0-10 was noted.
      RESULTS: All patients who used PCA were able to tolerate and complete the
      procedure with a median pain score of 0 (range, 0-2). Implants packed with the
      VBP method under PCA (n = 21) versus VGP under GA (n = 40) had significantly
      lower doses to the bladder D2cc (85.7% vs 104.8% of prescription dose), and
      rectum ICRU dose point (55.4% vs 65.2% of prescription dose), P = .0371 and .039,
      respectively. The ICRU bladder point and rectum D2cc between the 2 groups were
      not significantly different. CONCLUSIONS: Our results demonstrate that PCA is a
      feasible method for pain control for T&O brachytherapy. VBP and PCA are
      compatible with T&O brachytherapy and resulted in comparable if not better
      bladder and rectal dosimetry.

PMID- 24674397
TI  - Comparing the rates of urinary tract infections among patients receiving adjuvant
      pelvic intensity modulated radiation therapy, 3-dimensional conformal radiation
      therapy, and brachytherapy for newly diagnosed endometrial cancer.
AB  - PURPOSE: The purpose of this study was to compare the rates of urinary tract
      infection (UTI) among patients with endometrial cancer receiving vaginal
      brachytherapy alone and brachytherapy plus 3-dimensional conformal radiation
      therapy (3DCRT) or intensity modulated radiation therapy (IMRT). METHODS AND
      MATERIALS: We retrospectively evaluated the rates of UTI among 581 patients
      diagnosed with endometrial cancer, treated between 2004 and 2012. A total of 37%
      (216/581) received brachytherapy alone, 28% (161/581) received brachytherapy plus
      3DCRT, and 35% (204/581) received brachytherapy plus IMRT. UTI during the
      treatment was defined as evidence of pyuria detected by either urine dipstick or
      urinalysis. All specimens were collected as a clean catch, midstream void to
      avoid contamination and resultant false positives. The chi(2) and logistic
      regression analyses were subsequently employed for statistical analyses. RESULTS:
      UTI was diagnosed in 14.6% (85/581) of all patients. Only 2.8% (6/216) of
      patients receiving brachytherapy were diagnosed with a UTI during treatment,
      whereas UTI was diagnosed in 37.3% (60/161) of patients receiving brachytherapy
      plus 3DCRT, and 9.3% (19/204) of patients receiving brachytherapy plus IMRT (P <
      .0005). Logistic regression analysis found a decreased association between UTI
      and stage III endometrial cancer (odds ratio [OR], 0.51, 95% confidence interval
      [CI], 0.26, 0.99; P = .048). When compared with brachytherapy, both types of
      external beam radiation therapy were associated with an increased risk of UTI,
      though adjuvant 3DCRT (OR, 47.52, 95% CI, 14.81, 152.47; P < .001) had a more
      dramatic risk increase than IMRT (7.89, 95% CI, 2.26, 27.62; P = .001).
      CONCLUSIONS: When compared with IMRT, 3DCRT is associated with a significantly
      increased risk of UTI, supporting the use of IMRT as the less toxic external beam
      radiation therapy for endometrial cancer.

PMID- 24674398
TI  - Radiation therapy for sinonasal inverted papilloma.
AB  - PURPOSE: We retrospectively reviewed long-term outcomes of patients with inverted
      papilloma (IP) treated with radiation therapy at our institution. METHODS AND
      MATERIALS: From 1969 to 2008, 13 patients with advanced or recurrent IP (n = 12)
      or cylindrical papilloma (n = 1) were treated with radiation therapy. The median
      age at radiation therapy was 53 years old (range, 32-84). Nine patients received
      postoperative radiation therapy, 3 received definitive radiation therapy, and 1
      received preoperative radiation therapy. Of the 10 patients treated with combined
      modality treatment, 1 underwent craniofacial resection and 9 underwent open
      resection. Eight patients, 4 patients, and 1 patient received once-daily
      fractionation, twice-daily fractionation, and planned split-course radiation
      therapy, respectively, to a median dose of 65 Gy (range, 45.3-70.4 Gy). RESULTS:
      The median follow-up was 16.2 years. Actuarial 15-year overall and cause-specific
      survival rates were 62% and 82%. Fifteen-year actuarial local and regional
      control rates were 45% and 73%. Fifteen-year local-regional control rates for IP
      alone and IP associated with squamous cell carcinoma (IP-SCC) at the time of
      treatment were 80% and 16%. Fifteen-year overall survival rates for IP alone and
      IP-SCC were 40% and 50%. The only severe treatment complication was a grade 3
      central nervous system radionecrosis. The most common grade 1-2 toxicities were
      mucositis (61%), pain (46%), conjunctivitis (31%), xerostomia (31%), epiphora
      (31%), and anorexia (31%). CONCLUSIONS: While surgery is the primary treatment
      for IP, radiation therapy should be considered in patients with SCC, multiply
      recurrent IPs, and incompletely resectable IP. Radiation therapy is associated
      with a relatively low risk of severe complications. Despite more aggressive
      treatment, local failure remains a considerable challenge.

PMID- 24674399
TI  - Dosimetric feasibility of sparing the primary site for oropharyngeal squamous
      cell carcinoma after transoral laser microsurgery in patients with unilateral
      positive neck nodes.
AB  - PURPOSE: To quantify the effect of sparing the primary site after transoral laser
      microsurgery (TLM) for oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND
      MATERIALS: We reviewed 4 patients with OPSCC who were treated with TLM and
      postoperative radiation. All patients had T1 base of tongue primaries with the
      following N stages: 1 N1; 2 N2a; and 1 N2b. Three were lateralized to the right
      and 1 lateralized to the left. The primary site was not spared initially. We
      created new intensity modulated radiation treatment (IMRT) plans that spared the
      primary site. The prescribed dose to the high-risk (HR) and standard-risk (SR)
      planning target volumes (PTVs) was 60 Gy and 46 Gy at 2 Gy/fraction. PTV-SR and
      PTV-HR were adjusted to exclude the primary site. The primary site was maximally
      spared while maintaining similar PTV coverage and normal tissue avoidance as the
      initial plan. Dosimetric comparisons were made between the initial and primary
      site sparing IMRT plans. RESULTS: Dosimetric coverage of the PTVs and normal
      tissues (pharyngeal constrictors, contralateral parotid, etc) were comparable.
      The mean dose to the primary site was reduced by 20 Gy. The mean dose to the oral
      cavity was reduced by 25 Gy. CONCLUSIONS: This study suggests that omitting the
      primary site from the radiation therapy target volume is unlikely to reduce long
      term swallowing function to a meaningful degree in patients who receive radiation
      therapy following TLM for base of tongue cancer.

PMID- 24674400
TI  - Patterns of regional failure in stage III non-small cell lung cancer treated with
      neoadjuvant chemoradiation therapy and resection.
AB  - PURPOSE: Treatment of locally advanced non-small cell lung cancer (LA-NSCLC)
      involves definitive chemoradiation therapy (CRT) or neoadjuvant CRT and
      resection, but radiation treatment volumes remain in question. With CRT, involved
      field radiation therapy (IFRT) is replacing elective nodal irradiation, reducing
      toxicity, and allowing dose escalation. However, prior reports of IFRT describe
      failures only after radical CRT; with improved local control after resection,
      IFRT may lead to more regional recurrences. Our objective is to evaluate pattern
      of-failure in patients with LA-NSCLC treated with split-course IFRT,
      chemotherapy, and subsequent surgery. METHODS AND MATERIALS: Patients treated
      between December 2004 and 2010 were included. Imaging scans demonstrating failure
      were fused into the radiation therapy planning computed tomography, and recurrent
      nodes were contoured to determine pattern-of-failure (involved versus elective
      nodal failure [INF vs ENF]). Locoregional progression-free survival and distant
      metastasis-free survival were calculated using Kaplan-Meier methodology. The
      cumulative incidence of regional recurrence (CIRR) was determined with death as a
      competing risk. RESULTS: Forty-five patients met inclusion criteria, and patients
      with RR had a lower rate of pN0 than those without RR (20% vs 60%, P = .02). With
      a median follow-up of 2.9 years, median survival was not reached, and 3-year
      locoregional progression-free survival and distant metastasis-free survival were
      53% and 35%, respectively. Two and 3-year CIRR were 25% and 33%, respectively.
      There were no local failures. Thirteen (29%) patients had RR, 8 with INF only and
      5 with ENF alone or both, totaling 27 recurrences. Only 2 (4%) ENF occurred
      without INF, both with distant metastasis, and no elective node was the first and
      only site of failure. CONCLUSIONS: Our data suggest that IFRT does not compromise
      regional control in the neoadjuvant management of LA-NSCLC. Tailoring nodal
      volumes may improve treatment-related morbidity and allow for dose
      intensification of involved nodes. Further research is necessary to improve
      regional and distant control.

PMID- 24674401
TI  - Clinical impact of dose overestimation by effective path length calculation in
      stereotactic ablative radiation therapy of lung tumors.
AB  - PURPOSE: To determine the clinical impact of calculated dose differences between
      effective path length (EPL) and Monte Carlo (MC) algorithms in stereotactic
      ablative radiation therapy (SABR) of lung tumors. METHODS AND MATERIALS: We
      retrospectively analyzed the treatment plans and clinical outcomes of 77
      consecutive patients treated with SABR for 82 lung tumors between 2003 and 2009
      at our institution. Sixty treatments were originally planned using EPL, and 22
      using MC. All plans were recalculated for the same beam specifications using MC
      and EPL, respectively. The doses covering 95%, 50%, and 5% (D95, D50, D5,
      respectively) of the target volumes were compared between EPL and MC (assumed to
      be the actual delivered dose), both as physical dose and biologically effective
      dose. Time to local recurrence was correlated with dose by Cox regression
      analysis. The relationship between tumor control probability (TCP) and
      biologically effective dose was determined via logistic regression and used to
      estimate the TCP decrements due to prescribing by EPL calculations. RESULTS: EPL
      overestimated dose compared with MC in all tumor dose-volume histogram parameters
      in all plans. The difference was >10% of the MC D95 to the planning target volume
      and gross tumor volume in 60 of 82 (73%) and 52 of 82 plans (63%), respectively.
      Local recurrence occurred in 13 of 82 tumors. Controlling for gross tumor volume,
      higher physical and biologically effective planning target volume D95 correlated
      significantly with local control (P = .007 and P = .045, respectively). Compared
      with MC, prescribing based on EPL translated to a median TCP decrement of 4.3%
      (range, 1.2%-37%) and a >5% decrement in 46% of tumors. CONCLUSIONS: Clinical
      follow-up for local lung tumor control in a sizable cohort of patients treated
      with SABR demonstrates that EPL overestimates dose by amounts that substantially
      decrease TCP in a large proportion. EPL algorithms should be avoided for lung
      tumor SABR.

PMID- 24674403
TI  - A moving target: Image guidance for stereotactic body radiation therapy for early
      stage non-small cell lung cancer.
AB  - PURPOSE: Precise patient positioning is critical due to the large fractional
      doses and small treatment margins employed for thoracic stereotactic body
      radiation therapy (SBRT). The goals of this study were to evaluate the following:
      (1) the accuracy of kilovoltage x-ray (kV x-ray) matching to bony anatomy for
      pretreatment positioning; (2) the magnitude of intrafraction tumor motion; and
      (3) whether treatment or patient characteristics correlate with intrafraction
      motion. METHODS AND MATERIALS: Eighty-seven patients with lung cancer were
      treated with SBRT. Patients were positioned with orthogonal kV x-rays matched to
      bony anatomy followed by cone-beam computed tomography (CBCT), with matching of
      the CBCT-visualized tumor to the internal gross target volume obtained from a 4
      dimensional CT simulation data set. Patients underwent a posttreatment CBCT to
      assess the magnitude of intrafraction motion. RESULTS: The mean CBCT-based shifts
      after initial patient positioning using kV x-rays were 2.2 mm in the vertical
      axis, 1.8 mm in the longitudinal axis, and 1.6 mm in the lateral axis (n = 335).
      The percentage of shifts greater than 3 mm and 5 mm represented 39% and 17%,
      respectively, of all fractions delivered. The mean CBCT-based shifts after
      treatment were 1.6 mm vertically, 1.5 mm longitudinally, and 1.1 mm laterally (n
      = 343). Twenty-seven percent and 10% of shifts were greater than 3 mm and 5 mm,
      respectively. Univariate and multivariable analysis demonstrated a significant
      association between intrafraction motion with weight and pulmonary function.
      CONCLUSIONS: Kilovoltage x-ray matching to bony anatomy is inadequate for
      accurate positioning when a conventional 3-5 mm margin is employed prior to lung
      SBRT. Given the treatment techniques used in this study, CBCT image guidance with
      a 5-mm planning target volume margin is recommended. Further work is required to
      find determinants of interfraction and intrafraction motion that may help guide
      the individualized application of planning target volume margins.

PMID- 24674402
TI  - Stereotactic body radiation therapy-based treatment model for stage I medically
      inoperable small cell lung cancer.
AB  - PURPOSE: To report on medically inoperable stage I small cell lung cancer (SCLC)
      patients for whom stereotactic body radiation therapy (SBRT) was employed to
      manage the primary tumor. METHODS AND MATERIALS: Review of our institutional
      review board approved SBRT registry revealed 6 cases of stage I SCLC out of 430
      patients over a 6-year interval (2004-2010). All patients had biopsy proven
      disease and deemed medically inoperable by a thoracic surgeon. Our institutional
      approach was to treat with a combination of SBRT, platinum-etoposide chemotherapy
      (CHT) and prophylactic cranial irradiation (PCI). SBRT was delivered using a
      Novalis/BrainLAB platform and ExacTrac (BrainLab, Westchester, IL) for image
      guidance. RESULTS: Patient characteristics included a median Karnofsky
      performance scale of 80, a median age of 68 years, 4 females, and 1 patient still
      smoking at presentation. Impaired pulmonary function caused inoperability in 50%
      of cases. Tumor characteristics included median tumor size of 2.6 cm and median
      positron emission tomography-standard uptake valuemax of 9. The SBRT was 60 Gy/3
      fractions (3 patients), 50 Gy/5 fractions (2 patients), 30 Gy/1 fraction (1
      patient). Median follow-up was 11.9 months. There was no grade 3 or higher, and 1
      grade 2, toxicity. Three patients were alive at analysis and 3 patients had died
      of non-cancer causes. At 1 year, local control was 100%, there was no regional
      nodal failure, and 1 patient had distant failure (liver). Overall and disease
      free survivals at 1 year were 63% and 75%, respectively. CONCLUSIONS: Employing
      SBRT for stage I medically inoperable SCLC is rational, with excellent local
      control and encouraging disease-specific survival. The absence of regional nodal
      failure supports positron emission tomography for mediastinal staging. Platinum
      based CHT may be feasible in vulnerable populations.

PMID- 24674404
TI  - Feasibility and toxicity of hypofractionated image guided radiation therapy for
      large volume limited metastatic disease.
AB  - PURPOSE: Hypofractionated image guided radiation therapy (HIGRT) is increasingly
      used for limited metastases. Reported studies have mostly treated small volume
      tumors. Here, we report the toxicity and oncologic outcomes following treatment
      of large volume metastases. METHODS AND MATERIALS: HIGRT patients treated from
      October 2005 to March 2010 were reviewed. Gross tumor volumes (GTV) and planning
      target volumes (PTV) were obtained from planning software. A metastasis was
      considered large volume if the treated PTV exceeded 50 cc. Patients were treated
      with either 10-fraction (4-5 Gy per fraction) or 3-5 fraction (8-14 Gy per
      fraction) regimens. Toxicity was obtained from both prospectively collected
      databases and retrospectively from patient charts. RESULTS: Sixty-four patients
      with 93 treated lesions >50 cc were identified. The median GTV and PTV volumes
      were 41 and 119 cc, respectively. The median number of treated large volume
      lesions was 1, and a maximum of 3 large volume lesions were treated in a single
      patient. Primary malignancies included non-small cell lung cancer, renal cell,
      colorectal, breast, bladder, pituitary, small cell lung cancer, sarcoma, head-and
      neck cancer, and hepatocellular cancer. Treated sites included lung (n = 33),
      regional lymph nodes (n = 20), bone (n = 17), adrenal (n = 9), and liver (n = 6).
      The most frequently used treatment regimen was 50 Gy in 5 Gy fractions. The
      median follow-up was 27 months for surviving patients. Treated lesion control was
      78%. Low rates of acute and late grade 3 or higher toxicity were reported, with 3
      and 5 patients experiencing each, respectively. CONCLUSIONS: HIGRT to large
      volume oligometastatic disease is tolerable and feasible with promising tumor
      control. Local radiation therapy should be considered in patients with large
      volume, limited metastatic disease.

PMID- 24674405
TI  - Late toxicity after intensity modulated and image guided radiation therapy for
      localized prostate cancer and post-prostatectomy patients.
AB  - PURPOSE: To examine late gastrointestinal (GI) and genitourinary (GU) toxicity
      profiles of patients treated for prostate cancer either definitively or post
      prostatectomy with both intensity modulated radiation therapy (IMRT) and image
      guided radiation therapy (IGRT). METHODS AND MATERIALS: A total of 333 patients
      treated definitively and 104 patients treated postoperatively with IMRT and
      varying IGRT techniques were retrospectively examined to evaluate GI and GU
      toxicity profiles >1 year from treatment. Available dosimetric data were used for
      correlative analysis. RESULTS: The median follow-up time for the definitive
      patients was 41 months and the median follow-up time for the post-prostatectomy
      patients was 33 months. No late grade 4 or 5 GI or GU toxicities were observed.
      For definitive patients, the rates of grade >=2 GI and GU toxicity at 3 years
      were 4.9% and 4.5%, respectively. In the postoperative cohort the rate of grade
      >2 GU toxicity was 11.6%, with no grade >=2 GI toxicity. In the definitive
      cohort's Cox proportional hazards regression univariate analysis, use of
      anticoagulation was significantly associated with GI toxicity and age, bladder
      V50 and IGRT modality were associated with GU toxicity, and only age remained
      significant in the multivariate model. In univariate analysis for the
      postoperative cohort, no dosimetric value correlated with GU toxicity, nor did
      age or time from radical prostatectomy to radiation. CONCLUSIONS: IMRT with IGRT
      achieved low rates of GI and GU toxicity in the definitive and postoperative
      setting.

PMID- 24674406
TI  - Anatomic variation and dosimetric consequences of neoadjuvant hormone therapy
      before radiation therapy for prostate cancer.
AB  - PURPOSE: To characterize anatomic variation during neoadjuvant androgen
      deprivation (NAD) and determine a treatment planning strategy to maintain
      acceptable normal tissue dose while treating potential microscopic disease in the
      original (pre-NAD) tumor bed. METHODS AND MATERIALS: We retrospectively examined
      the effects of treating the post-NAD anatomy with plans derived before and after
      NAD in a group of 44 patients enrolled in an institutional review board-approved
      protocol. An 8-field intensity modulated radiation therapy (IMRT) treatment plan
      was generated on anatomy both before and after NAD for the first 35 patients. The
      pre-NAD treatment plan was applied to the post-NAD anatomy to evaluate the effect
      of complete pre-NAD tumor bed treatment on normal tissue sparing, and the post
      NAD treatment plan was applied to the pre-NAD anatomy to investigate whether
      microscopic disease might go untreated in the location of the pre-NAD tumor bed.
      RESULTS: The prostate decreased in volume by an average of about 14 cm(3) (24.3%)
      and was correlated with NAD duration (P = .002). The prostate center of volume
      systematically shifted in the inferior direction (mean = 1.4 mm, P = .005) and
      inferior shift was correlated with absolute volume reduction of the prostate (P =
      .044) in a multivariate model containing rectal and bladder volume change and
      initial prostate volume. Pre-NAD treatment planning resulted in a significant
      increase in the bladder volume (P < .01) but little increase in the rectal volume
      treated to all dose levels. Post-NAD treatment planning resulted in decreased
      treatment of the prostate and seminal vesicles (on the pre-NAD anatomy) at the
      prescribed and 95% isodose levels (prostate: P = .033 and 0.025; seminal
      vesicles: P < .001). CONCLUSIONS: Anisotropic volume reduction of the prostate
      was found during NAD and correlated with NAD duration. Post-NAD based treatment
      planning can minimize excess bladder and rectal dose.

PMID- 24674407
TI  - Growth abnormalities of the spine after radiation therapy: Respecting the past
      while moving forward in proton craniospinal irradiation.
AB  - Modern techniques of craniospinal radiation therapy (CSI) offer the advantage of
      modulating dose distribution to normal tissues in children and young adults.
      Reducing risks for second neoplasms and late effects to uninvolved tissues must
      be a priority for radiation oncologists. This manuscript reviews potential
      advantages and concerns moving forward with proton beam CSI. 

PMID- 24674408
TI  - Gastric bleeding after radiation therapy for intrahepatic cholangiocarcinoma.
AB  - PURPOSE: The goal of this study was to determine the incidence and risk factors
      associated with gastric bleeding in patients treated with radiation therapy for
      intrahepatic cholangiocarcinoma. METHODS AND MATERIALS: Between November 2002 and
      December 2008, 33 patients with intrahepatic cholangiocarcinoma were treated with
      radiation therapy to the primary site. Twenty-nine (88%) patients were previously
      treated with chemotherapy, including gemcitabine and cisplatin in 19 patients.
      The median dose of radiation therapy was 50.4 Gy (range, 35-70 Gy). Twenty-seven
      (82%) patients received concurrent therapy, with capecitabine in 26 and
      bevacizumab in 1 patient. RESULTS: Nine of the 33 patients developed gastric
      bleeding, with a 1-year actuarial rate of 36%. Of these 9 patients, 7 presented
      with bleeding symptoms and 2 presented with anemia. All 9 patients were
      documented to have gastritis on endoscopy. The absolute and percent volumes of
      stomach receiving 40 and 50 Gy were significantly associated with the risk of
      gastric bleeding. CONCLUSIONS: Patients with intrahepatic cholangiocarcinoma have
      a significant risk of developing gastric bleeding after radiation therapy. Hence,
      the volume of stomach exposed to radiation therapy should be minimized in
      patients receiving radiation therapy for intrahepatic cholangiocarcinoma.

PMID- 24674409
TI  - Daily setup uncertainty analysis for craniospinal irradiation using helical
      tomotherapy.
AB  - PURPOSE: Setup deviations of a craniospinal irradiation (CSI) patient cohort
      previously treated with helical tomotherapy were used to derive the optimal
      planning target volume (PTV) margin for CSI patients treated in the supine
      position. METHODS AND MATERIALS: The daily setup shifts of 27 CSI tomotherapy
      patients as determined using pretreatment megavoltage computed tomography
      verification for a total of 454 fractions were evaluated. Translational
      displacements in the mediolateral (ML), craniocaudal (CC), and anteroposterior
      (AP) directions were used to assess the systematic and random setup errors, and
      to derive the PTV margin required when daily image guidance is unavailable.
      RESULTS: The individual patient mean shifts and the corresponding standard
      deviations in the ML, CC, and AP directions were -0.5 +/- 2.1 mm, 1.0 +/- 2.7 mm,
      and 0.7 +/- 1.1 mm, respectively. The random errors in the corresponding
      directions were 1.9 mm, 1.9 mm, and 2.2 mm. The PTV margins required in the
      absence of daily imaging were 3.7 mm to the right, 4.7 mm to the left, 4.4 mm
      inferior, 6.4 mm superior, 1.6 mm posterior, and 3.0 mm anterior. CONCLUSIONS:
      The current PTV margin of 3.0 mm is sufficient to ensure clinical target volume
      coverage for CSI tomotherapy patients treated with daily megavoltage computed
      tomography imaging. When pretreatment verification imaging is not used to lower
      the setup uncertainty, a larger PTV margin of up to 6.4 mm in the CC direction
      will be needed.

PMID- 24674410
TI  - The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland
      in patients with breast cancer.
AB  - PURPOSE: The thyroid is not routinely considered an organ at risk in
      supraclavicular (SC) nodal radiation therapy (RT) for breast cancer. We compared
      the dosimetric impact of the following 2 RT planning techniques on the thyroid:
      (1) conventional single anterior field to encompass the SC nodal volume defined
      clinically; and (2) 3-dimensional conformal radiation therapy (3DCRT) planning to
      encompass the computed tomography (CT)-contoured SC nodal volume. METHODS AND
      MATERIALS: The thyroid, SC nodal volumes, and organs at risk were contoured on
      the planning CT of 20 patients who received 50 Gy in 2-Gy daily fractions to the
      breast or chest wall, and SC nodes. Comparisons of dosimetric parameters between
      the techniques were performed: thyroid, mean and maximum dose, V5, V30, and V50
      (percentage of thyroid receiving >=5 Gy, >=30 Gy, and >=50 Gy, respectively); SC
      nodal volume, homogeneity index (HI, percentage volume receiving 95%-107% of
      prescribed dose); and maximum doses of spinal cord and brachial plexus. Anatomic
      characteristics that influenced the dose distributions were investigated.
      RESULTS: The 3DCRT planning technique significantly increased all thyroid
      dosimetric measures (mean dose 17.2 Gy vs 26.7 Gy; maximum dose 48.5 Gy vs 51.9
      Gy; V5 45.7% vs 64.9%; V30 33.7% vs 48%; and V50 0.6% vs 26.7%; P < .001). It
      improved HI for the SC nodal volumes (P < .001) but resulted in higher maximum
      doses to the spinal cord (6.1 Gy vs 30 Gy) and brachial plexus (43.2 Gy vs 51.4
      Gy). The thyroid volume and depth of SC nodes did not influence the thyroid dose
      distribution. The depth of SC nodes impacted on the HI of SC nodal volumes in the
      conventional technique (P = .004). CONCLUSIONS: The 3DCRT planning improved
      dosimetric coverage of the SC nodal volume but increased thyroid radiation doses.
      The potential adverse effects of incidental thyroid irradiation should be
      considered while improving dosimetric coverage in SC nodal irradiation for breast
      cancer.

PMID- 24674412
TI  - Women at increased risk for cardiac toxicity following chemoradiation therapy for
      esophageal carcinoma.
AB  - PURPOSE: The purpose of this study was to identify factors associated with
      cardiac toxicity in patients treated with chemoradiation therapy (CRT) for
      esophageal carcinoma. METHODS AND MATERIALS: One hundred twenty-seven patients
      with adenocarcinoma or squamous cell carcinoma of the esophagus treated from July
      2002 to June 2011 at 2 academic institutions with preoperative or definitive CRT
      were retrospectively reviewed. Association of cardiac toxicity with a number of
      variables was investigated, including heart disease, cardiac bypass and
      angioplasty, diabetes, insulin use, smoking, chemotherapy regimen, and tumor
      location. T test assessed risk of cardiac toxicity secondary to age. Dose volume
      histograms (DVH) were evaluated for percentage of heart volume receiving >20, 30,
      40, and 50 Gy (V20-V50). The Fisher exact test analyzed for an association
      between dose volume parameters and cardiac toxicity. RESULTS: Patient population
      included 100 men and 27 women with a mean age of 64 years. Median follow-up was
      12.7 months (range, 0.3-99.6 months). Any cardiac toxicity occurred in 28
      patients, the majority of which were pericardial effusion (23/28). Odds ratio for
      toxicity in women was 4.15 (95% confidence interval [CI], 1.63-10.50; P = .0017)
      and time to cardiac toxicity by sex was significant (P = .0003). Patients above
      the median cutoff for V20, V30, and V40 had increased odds of developing cardiac
      toxicity (P = .03, .008, .002). There was 4.0 increased odds of developing
      cardiac toxicity with V40 >57% (95% CI, 1.5-10.3, P = .002). On multivariable
      logistic regression analysis, sex was the only variable associated with any
      cardiac toxicity and pericardial effusion (P = .0016, P = .0038). None of the
      other investigated variables were associated with increased risk of cardiac
      toxicity. CONCLUSIONS: Female patients and dose greater than the median for V20
      V40 were associated with the development of cardiac toxicity, specifically
      pericardial effusion. These data suggest exercising increased care when designing
      radiation fields in women undergoing CRT for esophageal carcinoma, as pericardial
      effusion may be a long-term complication.

PMID- 24674411
TI  - Automatic contouring of brachial plexus using a multi-atlas approach for lung
      cancer radiation therapy.
AB  - PURPOSE: To demonstrate a multi-atlas segmentation approach to facilitating
      accurate and consistent delineation of low-contrast brachial plexuses on computed
      tomographic images for lung cancer radiation therapy. METHODS AND MATERIALS: We
      retrospectively identified 90 lung cancer patients with treatment volumes near
      the brachial plexus. Ten representative patients were selected to form an atlas
      group, and their brachial plexuses were delineated manually. We used deformable
      image registration to map each atlas brachial plexus to the remaining 80
      patients. In each patient, a composite contour was created from 10 individual
      segmentations using the simultaneous truth and performance level estimation
      algorithm. This auto-delineated contour was reviewed and modified appropriately
      for each patient. We also performed 10 leave-one-out tests using the 10 atlases
      to validate the segmentation accuracy and demonstrate the contouring consistency
      using multi-atlas segmentation. RESULTS: The multi-atlas segmentation took less
      than 2 minutes to complete. Contour modification took 5 minutes compared with 20
      minutes for manual contouring from scratch. The multi-atlas segmentation from the
      10 leave-one-out tests had a mean 3-dimensional (3D) volume overlap of 59.2% +/-
      8.2% and a mean 3D surface distance of 2.4 mm +/- 0.5 mm. The distances between
      the individual and average contours in the 10 leave-one-out tests demonstrated
      much better contouring consistency for modified contours than for manual
      contours. The auto-segmented contours did not require substantial modification,
      demonstrated by the good agreement between the modified and auto-segmented
      contours in the 80 patients. Dose volume histograms of auto-segmented and
      modified contours were also in good agreement, showing that editing auto
      segmented contours is clinically acceptable in view of the dosimetric impact.
      CONCLUSIONS: Multi-atlas segmentation greatly reduced contouring time and
      improved contouring consistency. Editing auto-segmented contours to delineate the
      brachial plexus proved to be a better clinical practice than manually contouring
      from scratch.

PMID- 24674413
TI  - Reduced acute toxicity associated with the use of volumetric modulated arc
      therapy for the treatment of adenocarcinoma of the prostate.
AB  - PURPOSE: Novel techniques to deliver intensity modulated radiation therapy (IMRT)
      have resulted in improved treatment efficiency and dosimetric endpoints. We aimed
      to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity in
      patients treated for adenocarcinoma of the prostate (ACP) using volumetric
      modulated arc therapy (VMAT). METHODS AND MATERIALS: A total of 122 (71 IMRT and
      51 VMAT) ACP patients treated from 2004 to 2011 with definitive external beam
      radiation therapy were analyzed. Dose-volume histogram endpoints (V40, V65, V70,
      and V75 of the bladder and rectum) were collected for each patient. Median follow
      up for patients treated with VMAT was 269 days versus IMRT was 1121 days. Acute
      Common Toxicity Criteria for Adverse Events (CTCAE) GI and GU toxicity scores,
      obtained during each weekly treatment check, were compared across cohorts. The
      univariate (UV) association between the covariates and outcomes was assessed and
      multivariable (MV) cumulative logit models were fit for each outcome. RESULTS:
      Median patient age was 68 years and median prostate-specific antigen was 8.3.
      Both bladder and rectal V40, V65, V70, and V75 were all higher in the IMRT group
      versus the VMAT group (P < .05), which was likely influenced by larger planning
      target volumes in the IMRT group. The VMAT group had significantly lower rates of
      acute GU and acute GI CTCAE toxicity on UV association analysis. On MV analysis,
      VMAT remained independently associated with acute GU (odds ratio [OR], 0.18; 95%
      confidence interval [CI], 0.07-0.44; P < .001) and GI (OR, 0.16; 95% CI, 0.07
      0.41; P < .001) toxicity. CONCLUSIONS: VMAT appears to be independently
      associated with lower rates of acute GI and GU toxicity when compared with
      traditional IMRT. Further exploration of toxicity improvements associated with
      VMAT use in the definitive treatment of ACP is needed.

PMID- 24674414
TI  - National study to determine the comfort levels of radiation therapists and
      medical dosimetrists to report errors.
AB  - PURPOSE: Better understanding of the error reporting culture in radiation
      oncology treatment facilities, and obstacles to reporting, can provide insight
      into potential areas for improvement. We conducted a survey of radiation
      therapists and dosimetrists to examine the error reporting cultures in radiation
      oncology facilities across the United States and staff comfort in reporting
      errors. METHODS AND MATERIALS: In 2011, a national sample of 1500 radiation
      therapists and 528 dosimetrists was mailed a 27-item survey assessing perceptions
      regarding communication among staff, comfort in error reporting, and associated
      obstacles. Survey results were summarized using descriptive statistics, and
      factors associated with discomfort with error reporting analyzed using
      multivariate logistic regression. RESULTS: A total of 356 radiation therapists
      from 47 states (24% response rate) and 190 dosimetrists from 35 states (36%
      response rate) responded to the survey. Almost all (87% of therapists and 88% of
      dosimetrists) reported that there is an error reporting system in their treatment
      facility. Most feel that communication between them and physicians and
      dosimetrists or physicists (81% and 88% of therapists, and 89% and 88% of
      dosimetrists, respectively) is good, but only 65% of therapists and 66% of
      dosimetrists agree that communication with administrators is good. Obstacles to
      reporting errors included hierarchy within the treatment facility, poor
      communication, and fear of reprimand. On multivariate analysis, previous personal
      reprimand for reporting errors (odds ratio, 4.13, P = .001) and reprimand of
      other therapists and dosimetrists (odds ratio, 2.55, P = .03) were significantly
      associated with discomfort in error reporting. CONCLUSIONS: The majority of
      therapists and dosimetrists feel communication in their treatment facilities is
      good and that there are systems in place to report errors. A sizable minority
      reported experience with reprimand for error reporting that significantly reduced
      their comfort level with reporting errors. Obstacles identified in this study
      represent opportunities for future research and potential ways for improvement in
      radiation oncology treatment facilities.

PMID- 24674415
TI  - Subjective and objective quantification of physician's workload and performance
      during radiation therapy planning tasks.
AB  - PURPOSE: To quantify, and compare, workload for several common physician-based
      treatment planning tasks using objective and subjective measures of workload. To
      assess the relationship between workload and performance to define workload
      levels where performance could be expected to decline. METHODS AND MATERIALS:
      Nine physicians performed the same 3 tasks on each of 2 cases ("easy" vs "hard").
      Workload was assessed objectively throughout the tasks (via monitoring of pupil
      size and blink rate), and subjectively at the end of each case (via National
      Aeronautics and Space Administration Task Load Index; NASA-TLX). NASA-TLX
      assesses the 6 dimensions (mental, physical, and temporal demands, frustration,
      effort, and performance); scores > or ~ 50 are associated with reduced
      performance in other industries. Performance was measured using participants'
      stated willingness to approve the treatment plan. Differences in subjective and
      objective workload between cases, tasks, and experience were assessed using
      analysis of variance (ANOVA). The correlation between subjective and objective
      workload measures were assessed via the Pearson correlation test. The
      relationships between workload and performance measures were assessed using the t
      test. RESULTS: Eighteen case-wise and 54 task-wise assessments were obtained.
      Subjective NASA-TLX scores (P < .001), but not time-weighted averages of
      objective scores (P > .1), were significantly lower for the easy vs hard case.
      Most correlations between the subjective and objective measures were not
      significant, except between average blink rate and NASA-TLX scores (r = -0.34, P
      = .02), for task-wise assessments. Performance appeared to decline at NASA-TLX
      scores of >=55. CONCLUSIONS: The NASA-TLX may provide a reasonable method to
      quantify subjective workload for broad activities, and objective physiologic eye
      based measures may be useful to monitor workload for more granular tasks within
      activities. The subjective and objective measures, as herein quantified, do not
      necessarily track each other, and more work is needed to assess their utilities.
      From a series of controlled experiments, we found that performance appears to
      decline at subjective workload levels >=55 (as measured via NASA-TLX), which is
      consistent with findings from other industries.

PMID- 24674416
TI  - Quantifying the impact of cross coverage on physician's workload and performance
      in radiation oncology.
AB  - PURPOSE: To quantitatively assess the difference in workload and performance of
      radiation oncology physicians during radiation therapy treatment planning tasks
      under the conditions of "cross coverage" versus planning a patient with whom they
      were familiar. METHODS AND MATERIALS: Eight physicians (3 experienced faculty
      physicians and 5 physician residents) performed 2 cases. The first case
      represented a "cross-coverage" scenario where the physicians had no prior
      information about the case to be planned. The second exposure represented a
      "regular-coverage" scenario where the physicians were familiar with the patient
      case to be planned. Each case involved 3 tasks to be completed systematically.
      Workload was assessed both subjectively (perceived) using National Aeronautics
      and Space Administration-Task Load Index (NASA-TLX), and objectively
      (physiological) throughout the task using eye data (via monitoring pupil size and
      blink rate). Performance of each task and the case was measured using completion
      time. Subjective willingness to approve or disapprove the generated plan was
      obtained after completion of the case only. RESULTS: Forty-eight perceived and 48
      physiological workload assessments were obtained. Overall, results revealed a
      significant increase in perceived workload (high NASA-TLX score) and decrease in
      performance (longer completion time and reduced approval rate) during cross
      coverage. There were nonsignificant increases in pupil diameter and decreases in
      the blink rate during cross-coverage versus regular-coverage scenario. In both
      cross-coverage and regular-coverage scenarios the level of experience did not
      affect workload and performance. CONCLUSIONS: The cross-coverage scenario
      significantly increases perceived workload and degrades performance versus
      regular coverage. Hence, to improve patient safety, efforts must be made to
      develop policies, standard operating procedures, and usability improvements to
      electronic medical record and treatment planning systems for "easier" information
      processing to deal with cross coverage, while recognizing strengths and
      limitations of human performance.

PMID- 24674417
TI  - Reducing posttreatment dysphagia: Support for the relationship between radiation
      dose to the pharyngeal constrictors and swallowing outcomes.
AB  - PURPOSE: This study used prospective swallowing data to establish the following:
      (1) whether doses to the pharyngeal constrictor muscles (PCMs) were significantly
      associated with swallowing outcomes; and (2) a mean dose constraint to aim for in
      intensity modulated radiation therapy planning. METHODS AND MATERIALS: The PCMs
      were contoured and radiation dose data obtained for 55 patients with head and
      neck cancer. Associations between radiation dose and percentage of pharyngeal
      residue, penetration-aspiration and activity limitation measured at 6 months
      posttreatment were analyzed. Pretreatment swallowing function, tumor site, T
      classification, and chemotherapy were accounted for in multivariate analyses.
      RESULTS: On multivariate analysis, the percentage of pharyngeal residue was
      statistically significantly associated with the mean dose to the superior PCM
      (95% confidence interval [CI], 0.15-1.66; P = .02). Penetration-aspiration was
      associated with the mean dose to the superior, middle, and inferior PCMs (95% CI,
      1.02-1.27; P = .003; 95% CI, 1.02-1.23; P = .003; 95% CI, 1.04-1.21; P = .003,
      respectively) and the mean dose to the total PCM (95% CI, 1.05-1.31; P = .001).
      Activity limitation was also associated with the mean dose to the superior,
      middle, and inferior PCMs (95% CI, 1.01-1.20; P = .02; 95% CI, 1.00-1.15; P =.04;
      95% CI, 1.01-1.15; P = .02, respectively) and the mean dose to the total PCM (95%
      CI, 1.02-1.23; P = .01). On univariate analysis, all 3 swallowing measures were
      statistically significantly worse for patients who received a biologically
      equivalent mean dose of >60 Gy to the PCMs. This remained significant on
      multivariate analysis for both penetration-aspiration and activity limitation
      (95% CI, 2.05-58.2, P = .004 and 95% CI, 1.14-27.7, P = .03, respectively).
      CONCLUSIONS: The radiation dose to the PCMs is significantly associated with
      swallowing dysfunction. Limiting the mean PCM dose to less than 60 Gy results in
      better swallowing outcomes.

PMID- 24674418
TI  - Radiation-induced dermatitis with vemurafenib therapy.

PMID- 24674419
TI  - Initial experience with TrueBeam trajectory log files for radiation therapy
      delivery verification.
AB  - PURPOSE: Traditionally, initial and weekly chart checks involve checking various
      parameters in the treatment management system against the expected treatment
      parameters and machine settings. This process is time-consuming and labor
      intensive. We explore utilizing the Varian TrueBeam log files (Varian Medical
      System, Palo Alto, CA), which contain the complete delivery parameters for an end
      to-end verification of daily patient treatments. METHODS AND MATERIALS: An in
      house software tool for 3-dimensional (3D) conformal therapy, enhanced dynamic
      wedge delivery, intensity modulated radiation therapy (IMRT), volumetric
      modulated radiation therapy, flattening filter-free mode, and electron therapy
      treatment verification was developed. The software reads the Varian TrueBeam log
      files, extracts the delivered parameters, and compares them against the original
      treatment planning data. In addition to providing an end-to-end data transfer
      integrity check, the tool also verifies the accuracy of treatment deliveries.
      This is performed as part of the initial chart check for IMRT plans and after
      first fraction for the 3D plans. The software was validated for consistency and
      accuracy for IMRT and 3D fields. RESULTS: Based on the validation results the
      accuracy of MLC, jaw and gantry positions were well within the expected values.
      The patient quality assurance results for 127 IMRT patients and 51 conventional
      fields were within 0.25 mm for multileaf collimator positions, 0.3 degree for
      gantry angles, 0.13 monitor units for monitor unit delivery accuracy, and 1 mm
      for jaw positions. The delivered dose rates for the flattening filter-free modes
      were within 1% of the planned dose rates. CONCLUSIONS: The end-to-end data
      transfer check using TrueBeam log files and the treatment delivery parameter
      accuracy check provides an efficient, reliable beam parameter check process for
      various radiation delivery techniques.

PMID- 24674420
TI  - A comparison of phase, amplitude, and velocity binning for cone-beam computed
      tomographic projection-based motion reconstruction.
AB  - PURPOSE: We previously developed a motion estimation technique based on direct
      cone-beam projection analysis. It is able to reconstruct the complete motion
      trajectory of a radio-opaque marker, including cycle-to-cycle variability, using
      respiratory binning of the projection images. This paper investigates the use of
      phase, amplitude, and amplitude-velocity binning in the context of projection
      based cone-beam motion estimation (CBME). METHODS AND MATERIALS: We simulated
      cone-beam computed tomographic scans of 160 tumor trajectories estimated by a
      CyberKnife Synchrony System (Accuray, Sunnyvale, CA), and reconstructed the
      complete trajectory with CBME using phase, amplitude, and amplitude-velocity
      binning of the projection data. Various numbers of respiratory bins, from 1 (no
      binning) to 100, were used for phase and amplitude binning, while 1 to 100
      amplitude bins with 4 velocity bins were used for amplitude-velocity binning.
      From this large pool of data, we correlated the reconstruction accuracy with bin
      type, total number of bins, number of breathing cycles per bin, and the position
      of the bin within the breathing cycle. RESULTS: CBME predicted the true motion of
      the marker with a 3-dimensional (3D) mean root mean square (RMS) error of 0.24 mm
      for amplitude-velocity binning, 0.31 mm for amplitude binning, and 0.52 mm for
      phase binning. Reconstruction 3D RMS error increased to over 1 mm when less than
      3 breathing cycles contributed to a bin. We found that reconstruction accuracy
      was optimized when about 20 bins were used. Accuracy also decreased in bins
      located around the inhale portion of the breath cycle, compared with the mid- and
      end-exhale positions. CONCLUSIONS: This study provides a quantitative assessment
      of phase, amplitude, and amplitude-velocity binning for CBME. A joint binning
      approach should be used to give both the accuracy of amplitude binning, as well
      as the robustness of phase binning, in areas of limited motion sampling.

PMID- 24674421
TI  - A global perspective on adolescent pregnancy.
AB  - Adolescent pregnancy is an international dilemma affecting not just the
      adolescent and her infant, but entire societies. Of almost 300 million female
      adolescents worldwide, 16 million give birth yearly, accounting for 11% of all
      births worldwide. The Millennium Development Goal # 5 incorporates reducing
      adolescent births worldwide. The purpose of this paper is a comprehensive
      critique of findings on a global perspective on adolescent pregnancy and
      evaluation of strategies to reduce this international concern. In Latin America
      and the Caribbean, unmet need for family planning made little change in 20 years.
      In Dutch and Scandinavian countries, there are national sex education programmes
      and family planning clinics run by nurse midwives with direct authority to
      prescribe contraceptives. In Japan, strong conservative norms exist about
      premarital sex. In the UK, a lack of consistent targeted sex education, delay in
      access to contraception and contraceptive use failure are associated with high
      teen pregnancy rates. In the United States, 750,000 teen pregnancies occur
      yearly, costing $9 billion per year. Health disparities exist: Whites had 11,
      Blacks had 32 and Hispanics had 41 per 1000 births. Programmes to reduce teen
      pregnancy should incorporate family, contraception and abstinence education, and
      sustained commitment of media, businesses, religious and civic organizations.

PMID- 24674422
TI  - Ring cell migration assay identifies distinct effects of extracellular matrix
      proteins on cancer cell migration.
AB  - BACKGROUND: Alterations in cell migration are a hallmark of cancer cell invasion
      and metastasis. In vitro assays commonly used to study cell migration, including
      the scratch wound healing assay, Boyden chamber assay, and newly developed
      advanced systems with microfluidics, each have several disadvantages. FINDINGS:
      Here we describe an easy and cost-effective in vitro assay for cell migration
      employing cloning rings to create gaps in the cell monolayer ("ring cell
      migration assay"). The assay was used to quantitate innate differences in cell
      motility and the effect of various extracellular matrix proteins on migration of
      five cancer cell lines: U87 and U251N glioma cells, MDA-MB-231 and MCF-7 breast
      cancer cells, and HeLa cervical cancer cells. Interestingly, collagen was a
      general promoter of cell migration for all five cancer cell lines, without
      affecting cell proliferation. CONCLUSIONS: Taken together, the ring cell
      migration assay is an easy, convenient and cost-effective assay to study cell
      migration in vitro.

PMID- 24674423
TI  - Population structure of four Thai indigenous chicken breeds.
AB  - BACKGROUND: In recent years, Thai indigenous chickens have increasingly been bred
      as an alternative in Thailand poultry market. Due to their popularity, there is a
      clear need to improve the underlying quality and productivity of these chickens.
      Studying chicken genetic variation can improve the chicken meat quality as well
      as conserving rare chicken species. To begin with, a minimal set of molecular
      markers that can characterize the Thai indigenous chicken breeds is required.
      RESULTS: Using AFLP-PCR, 30 single nucleotide polymorphisms (SNPs) from Thai
      indigenous chickens were obtained by DNA sequencing. From these SNPs, we
      genotyped 465 chickens from 7 chicken breeds, comprising four Thai indigenous
      chicken breeds--Pradhuhangdum (PD), Luenghangkhao (LK), Dang (DA) and Chee (CH),
      one wild chicken--the red jungle fowls (RJF), and two commercial chicken breeds-
      the brown egg layer (BL) and commercial broiler (CB). The chicken genotypes
      reveal unique genetic structures of the four Thai indigenous chicken breeds. The
      average expected heterozygosities of PD=0.341, LK=0.357, DA=0.349 and CH=0.373,
      while the references RJF= 0.327, CB=0.324 and BL= 0.285. The F(ST) values among
      Thai indigenous chicken breeds vary from 0.051 to 0.096. The F(ST) values between
      the pairs of Thai indigenous chickens and RJF vary from 0.083 to 0.105 and the
      FST values between the Thai indigenous chickens and the two commercial chicken
      breeds vary from 0.116 to 0.221. A neighbour-joining tree of all individual
      chickens showed that the Thai indigenous chickens were clustered into four groups
      which were closely related to the wild RJF but far from the commercial breeds.
      Such commercial breeds were split into two closely groups. Using genetic
      admixture analysis, we observed that the Thai indigenous chicken breeds are
      likely to share common ancestors with the RJF, while both commercial chicken
      breeds share the same admixture pattern. CONCLUSION: These results indicated that
      the Thai indigenous chicken breeds may descend from the same ancestors. These
      indigenous chicken breeds were more closely related to red jungle fowls than
      those of the commercial breeds. These findings showed that the proposed SNP panel
      can effectively be used to characterize the four Thai indigenous chickens.

PMID- 24674424
TI  - Self-reported hand washing behaviors and foodborne illness: a propensity score
      matching approach.
AB  - Hand washing is a simple and effective but easily overlooked way to reduce cross
      contamination and the transmission of foodborne pathogens. In this study, we used
      the propensity score matching methodology to account for potential selection bias
      to explore our hypothesis that always washing hands before food preparation tasks
      is associated with a reduction in the probability of reported foodborne illness.
      Propensity score matching can simulate random assignment to a condition so that
      pretreatment observable differences between a treatment group and a control group
      are homogenous on all the covariates except the treatment variable. Using the
      U.S. Food and Drug Administration's 2010 Food Safety Survey, we estimated the
      effect of self-reported hand washing behavior on the probability of self-reported
      foodborne illness. Our results indicate that reported washing of hands with soap
      always before food preparation leads to a reduction in the probability of
      reported foodborne illness. 

PMID- 24674425
TI  - Leveraging management strategies for seedborne plant diseases to reduce
      Salmonella enterica Serovar Typhimurium incidence on tomato seed and seedlings.
AB  - Tomatoes have been linked to many outbreaks of salmonellosis over the last
      decade, but the routes of contamination have yet to be discerned. Many
      phytopathogens of tomato are seedborne and are effectively managed using seed
      sanitizers. Seed sanitizers effective against bacterial phytopathogens were
      evaluated for their efficacy in killing bioluminescent Salmonella enterica
      serovar Typhimurium strain SeT-A14 on tomato seed infested with moderately high
      and high levels of pathogen. SeT-A14 incidence on seedlings produced from
      contaminated seed following sanitation was also determined. At a moderately high
      infestation rate (40%), SeT-A14 was eradicated on seed sanitized with 1.2% sodium
      hypochlorite (NaClO) mixed with 0.03% surfactant for 2 min, hydrochloric acid
      (HCl) for 30 min, and trichloromelamine for 2 min. At a higher infestation rate
      (94%), only NaClO and HCl were effective in eradicating SeT-A14 from the seed. At
      both infestation rates, 2% Virkon-S for 15 min significantly reduced SeT-A14
      incidence compared with the nontreated infested controls but did not eradicate
      the pathogen. Hot water, a commonly used sanitizer for managing seedborne
      bacterial plant diseases, significantly reduced SeT-A14 on heavily infested seed,
      but incidence was still moderate at 17.5%. On seedlings produced from moderately
      highly infested seed, SeT-A14 was not detected using RapidChek Salmonella test
      strips. Using heavily infested seed, SeT-A14 was detected with the test strips in
      one of four pooled samples of 14-day-old seedlings produced from nonsanitized
      seed and from seed sanitized with hot water and trichloromelamine. However,
      bioluminescence was not observed on 14-day-old seedlings. To our knowledge, this
      is the first report that provides evidence that S. enterica serovar Typhimurium
      can be seed transmitted and can lead to the contamination of tomato seedlings. In
      addition to eliminating important bacterial phytopathogens from tomato seed,
      NaClO or HCl may mitigate the risk of Salmonella seedling contamination. 

PMID- 24674426
TI  - Effects of postharvest handling conditions on internalization and growth of
      Salmonella enterica in tomatoes.
AB  - Salmonella internalization in tomatoes during postharvest handling is a major
      food safety concern. This study was conducted to determine the effect of
      immersion time, immersion depth, and temperature differential between bacterial
      suspension and tomato pulp on the internalization of Salmonella enterica in
      tomato fruits. The effect of storage temperature and duration on the survival and
      growth of internalized Salmonella cells was also evaluated. Overall, immersion
      time significantly affected the incidence and extent of S. enterica
      internalization (P < 0.0001), with a linear correlation between immersion time
      and Salmonella internalization. The depth of Salmonella internalization in tomato
      tissues also increased with increasing immersion time. Immersion time also
      significantly influenced the degree to which the temperature differential
      affected Salmonella internalization. With an immersion time of 2 min, the
      temperature differential had no significant effect on Salmonella internalization
      (P = 0.2536). However, with an immersion time of 15 min, a significantly larger
      Salmonella population became internalized in tomatoes immersed in solutions with
      a -30 degrees F (-16.7 degrees C) temperature differential. Internalized S.
      enterica cells persisted in the core tissues during 14 days of storage. Strain
      type and storage duration significantly affected (P < 0.05) both the frequency
      detected and the population of internalized Salmonella recovered, but storage
      temperatures of 55 to 70 degrees F (12.8 to 21.1 degrees C) did not (P > 0.05).
      These findings indicate the importance of preventing pathogen internalization
      during postharvest handling. 

PMID- 24674427
TI  - Evaluating Escherichia coli O157 control in finnish primary production.
AB  - Enterohemorrhagic Escherichia coli (EHEC) has become a threat in the modern
      cattle sector because of its adverse impact on human health. Systems have been
      developed to reduce the risk of EHEC infection associated with the beef
      production chain. In Finland, the risk management of EHEC is mainly targeted at
      primary production, which is controlled by a national program. The prevalence of
      E. coli O157 in slaughter animals and herds appears to have remained relatively
      low over the years (0.2 to 1.2% and 0.3 to 1.5%, respectively). The effectiveness
      of the Finnish EHEC control program (FECP) was analyzed with a Bayesian
      statistical model based on the results from 2006 through 2010. According to the
      model, the estimated true prevalence of EHEC in slaughter animals was at its
      highest in 2007 (95% credible interval [CI], 0.94 to 1.85% of animals), and the
      estimated true prevalence in herds was its highest in 2007 (95% CI, 1.28 to 2.55%
      of herds). However, the estimated probability of the FECP detecting an EHEC
      positive slaughter animal or herd was 0.52 to 0.58% and 4.74 to 6.49%,
      respectively. The inability to detect EHEC-positive animals was partly due to
      animal-based random sampling, which ignores herd-level testing and therefore
      emphasizes the testing of slaughter animals from herds that send more animals to
      slaughter. Some slaughterhouses collected samples incorrectly as a consequence of
      an incorrectly implemented FECP. Farmers may also have questionable reasons for
      choosing to send animals to be slaughtered in small abattoirs, in which testing
      is less likely, to avoid suspicion of EHEC or other zoonotic infections.

PMID- 24674428
TI  - Salmonella transfer during pilot plant scale washing and roller conveying of
      tomatoes.
AB  - Salmonella transfer during washing and roller conveying of inoculated tomatoes
      was quantified using a pilot scale tomato packing line equipped with plastic,
      foam, or brush rollers. Red round tomatoes (2.3 kg) were dip inoculated with
      Salmonella enterica serovar Typhimurium LT2 (avirulent) (4 log CFU/g), air dried
      for 2 h, and then washed in sanitizer-free water for 2 min. Inoculated tomatoes
      were then passed single file over a 1.5-m conveyor equipped with plastic, foam,
      or brush rollers followed by 25 previously washed uninoculated tomatoes. Tomato
      samples were collected after 2 min of both washing and roller conveying, with all
      25 uninoculated tomatoes collected individually after conveying. Roller surface
      samples were collected before and after conveying the uninoculated tomatoes. Both
      tomato and surface samples were quantitatively examined for Salmonella by direct
      plating or membrane filtration using xylose lysine Tergitol 4 agar. Regardless of
      the roller type, Salmonella populations on inoculated tomatoes did not
      significantly (P < 0.05) decrease during contact with the roller conveyors. After
      conveying uninoculated tomatoes over contaminated foam rollers, 96% of the 25
      tomatoes were cross-contaminated with Salmonella at >100 CFU per tomato. With
      plastic rollers, 24 and 76% of tomatoes were cross-contaminated with Salmonella
      at 10 to 100 and 1 to 10 CFU per tomato, respectively. In contrast, only 8% of 25
      tomatoes were cross-contaminated with brush rollers with Salmonella populations
      of 1 to 10 CFU per tomato. Overall, cross-contamination was greatest with foam,
      followed by plastic and brush rollers (P < 0.05). Adding peroxyacetic acid or
      chlorine to the wash water significantly decreased cross-contamination during
      tomato conveying, with chlorine less effective in controlling Salmonella on foam
      compared with plastic and brush rollers. 

PMID- 24674429
TI  - Prevalence and concentration of bacterial pathogens in raw produce and minimally
      processed packaged salads produced in and for the Netherlands.
AB  - Recent outbreaks with vegetable or fruits as vehicles have raised interest in the
      characterization of the public health risk due to microbial contamination of
      these commodities. Because qualitative and quantitative data regarding prevalence
      and concentration of various microbes are lacking, we conducted a survey to
      estimate the prevalence and contamination level of raw produce and the resulting
      minimally processed packaged salads as sold in The Netherlands. A dedicated
      sampling plan accounted for the amount of processed produce in relation to the
      amount of products, laboratory capacity, and seasonal influences. Over 1,800
      samples of produce and over 1,900 samples of ready-to-eat mixed salads were
      investigated for Salmonella enterica serovars, Campylobacter spp., Escherichia
      coli O157, and Listeria monocytogenes. The overall prevalence in raw produce
      varied between 0.11% for E. coli O157 and L. monocytogenes and 0.38% for
      Salmonella. Prevalence point estimates for specific produce/pathogen combinations
      ranged for Salmonella from 0.53% in iceberg lettuce to 5.1% in cucumber. For
      Campylobacter, this ranged from 0.83% in endive to 2.7% in oak tree lettuce.
      These data will be used to determine the public health risk posed by the
      consumption of ready-to-eat mixed salads in The Netherlands. 

PMID- 24674430
TI  - Microbiological risk from minimally processed packaged salads in the Dutch food
      chain.
AB  - The objective of this study was to evaluate the microbial hazard associated with
      the consumption of mixed salads produced under standard conditions. The presence
      of Salmonella, Campylobacter spp., and Escherichia coli O157 in the Dutch
      production chain of mixed salads was determined. Microbial prevalence and
      concentration data from a microbiological surveillance study were used as inputs
      for the quantitative microbial risk assessment. Chain logistics, production
      figures, and consumption patterns were combined with the survey data for the risk
      assessment chain approach. The results of the sample analysis were used to track
      events from contamination through human illness. Wide 95% confidence intervals
      around the mean were found for estimated annual numbers of illnesses resulting
      from the consumption of mixed salads contaminated with Salmonella Typhimurium
      DT104 (0 to 10,300 cases), Campylobacter spp. (0 to 92,000 cases), or E. coli (0
      to 800 cases). The main sources of uncertainty are the lack of decontamination
      data (i.e., produce washing during processing) and an appropriate dose-response
      relationship. 

PMID- 24674431
TI  - Comparison of baseline bacterial levels in retail ground beef originating from
      different regulatory, processing, and packaging environments.
AB  - The objectives of this study were to collect baseline measures of bacteria
      present in retail ground beef offered for sale in Saskatchewan and to assess
      differences associated with the licensing or regulatory environment of the
      packaging and processing facilities as indicated by package labeling. Packages of
      ground beef (n = 309) were purchased from May 2011 to May 2012. Retail samples
      were categorized as originating from facilities regulated by the federal
      government or licensed by the provincial government (n = 126), originating from
      facilities licensed by local health regions (n = 80), or having no inspection or
      source information on the package label (n = 103). Total aerobic plate counts and
      total Escherichia coli plate counts were determined using 3M Petrifilm methods.
      Total bacterial load was estimated using real-time quantitative PCR. The data
      were analyzed on a log scale using multivariable linear regression, accounting
      for season and whether the samples were fresh or frozen at purchase. Total
      aerobic plate counts and Escherichia coli plate counts were lower in samples from
      federally regulated or provincially licensed facilities than in samples from
      locally licensed facilities (P < 0.001 and P = 0.002, respectively) or in samples
      with no inspection information on the label (P < 0.001 and P = 0.011,
      respectively). Frozen ground beef from federally regulated or provincially
      licensed facilities had the lowest total bacterial load. Samples clearly labeled
      as packaged at federally regulated or provincially licensed facilities
      consistently had the lowest estimated bacterial levels. 

PMID- 24674432
TI  - Analysis of microbiological contamination in mixed pressed ham and cooked sausage
      in Korea.
AB  - The objective of this study was to investigate the microbial contamination levels
      (aerobic bacteria plate count [APC], coliforms, Escherichia coli, Staphylococcus
      aureus, and Listeria monocytogenes) in mixed pressed ham and cooked sausage. A
      total of 180 samples were collected from factories with and without hazard
      analysis critical control point (HACCP) systems at four steps: after chopping
      (AC), after mixing (AM), cooling after the first heating process, and cooling
      after the second heating process. For ham, APCs and coliform and E. coli counts
      increased when ingredients were added to the meat at the AC step. Final product
      APC was 1.63 to 1.85 log CFU/g, and coliforms and E. coli were not detected. S.
      aureus and L. monocytogenes were found in nine (15.0%) and six (10.0%) samples,
      respectively, but only at the AC and AM steps and not in the final product.
      Sausage results were similar to those for ham. The final product APC was 1.52 to
      3.85 log CFU/g, and coliforms and E. coli were not detected. S. aureus and L.
      monocytogenes were found in 29 (24.2%) and 25 (20.8%) samples at the AC and AM
      steps, respectively, but not in the final product. These results indicate that
      the temperature and time of the first and second heating are of extreme
      importance to ensure the microbiological safety of the final product regardless
      of whether a HACCP system is in place. Microorganism contamination must be
      monitored regularly and regulations regarding sanitization during processing
      should be improved. Education regarding employee personal hygiene, environmental
      hygiene, prevention of cross-contamination, ingredient control, and step-by-step
      process control is needed to reduce the risk of food poisoning. 

PMID- 24674433
TI  - Survival of foodborne pathogenic bacteria (Bacillus cereus, Escherichia coli
      O157:H7, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and
      Listeria monocytogenes) and Bacillus cereus spores in fermented alcoholic
      beverages (beer and refined rice wine).
AB  - Only limited information is available on the microbiological safety of fermented
      alcoholic beverages because it is still a common belief that such beverages do
      not provide a favorable environment for bacterial growth and survival. Thus, in
      this study, we examined the survival of major foodborne pathogens and spores in
      fermented alcoholic beverages. Foodborne pathogens (Bacillus cereus, Escherichia
      coli O157:H7, Listeria monocytogenes, Salmonella enterica serovar Typhimurium,
      and Staphylococcus aureus) and B. cereus spores (initial population, 3 to 4 log
      CFU/ml) were inoculated separately into three types of beer and refined rice
      wine, which were then stored at 5 and 22 degrees C. Bacterial counts were assayed
      periodically for up to 28 days. Vegetative B. cereus counts decreased rapidly,
      whereas B. cereus spore counts remained constant (P > 0.05) for a long period of
      time in all beverages. Vegetative B. cereus cells formed spores in beer at 5 and
      22 degrees C, and the spores survived for long periods. Among vegetative cells,
      E. coli O157:H7 had the highest survival (only 1.49 to 1.56 log reduction during
      28 days in beer at 5 degrees C). Beer and refined rice wine supported microbial
      survival from several days to several weeks. Our results appear to contradict the
      common belief that pathogens cannot survive in alcoholic beverages. Long-term
      survival of pathogens (especially B. cereus and E. coli O157:H7) in beer and
      refined rice wine should be taken into consideration by the manufacturers of
      these beverages. This study provides basic information that should help further
      research into microbial survival in alcoholic beverages and increase the
      microbiological safety regulation of fermented alcoholic beverages. 

PMID- 24674434
TI  - Attachment of Listeria innocua to polystyrene: effects of ionic strength and
      conditioning films from culture media and milk proteins.
AB  - It is recognized that bacterial adhesion usually occurs on conditioning films
      made of organic macromolecules absorbed to abiotic surfaces. The objectives of
      this study were to determine the extent to which milk protein-coated polystyrene
      (PS) pegs interfere with biofilm formation and the synergistic effect of this
      conditioning and hypertonic growth media on the bacterial adhesion and biofilm
      formation of Listeria innocua, used as a nonpathogenic surrogate for Listeria
      monocytogenes. PS pegs were uncoated (bare PS) or individually coated with whey
      proteins isolate (WPI), beta-lactoglobulin, bovine serum albumin, or tryptic soy
      broth (TSB) and were incubated in bacterial suspensions in modified Welshimer's
      broth. After 4 h, the number of adherent cells was dependent on the coating, as
      follows: TSB (10(7) CFU/ml) > bare PS > beta-lactoglobulin > bovine serum albumin
      ~ WPI (10(4) CFU/ml). The sessile cell counts increased up to 24 h, reaching >
      10(7) CFU per peg for all surfaces (P > 0.1), except for WPI-coated PS; this
      indicates that the inhibitory effects of milk protein conditioning films are
      transient, slowing down the adhesion process. The 4-h bacterial adhesion on milk
      protein-coated PS in modified Welshimer's broth supplemented with salt (0 to 10%
      [wt/vol]) did not vary (P > 0.1), indicating that conditioning with milk proteins
      was the major determinant for inhibition of bacterial adhesion and that the
      synergetic effect of salt and milk proteins on adhesion was minimal. Moreover,
      the presence of 5 to 10% salt significantly inhibited 24-h biofilm formation on
      the TSB-coated and bare PS, with a decrease of >3 log at 10% (wt/vol) NaCl and
      almost completely depleted viable sessile bacteria on the milk protein-coated PS.

PMID- 24674435
TI  - Characterization of Mexican coriander (Eryngium foetidum) essential oil and its
      inactivation of Listeria monocytogenes in vitro and during mild thermal
      pasteurization of pineapple juice.
AB  - The aim of this work was to characterize the essential oil (EO) of Eryngium
      foetidum (EfEO) and assess its activity toward Listeria monocytogenes in broth
      and during thermal inactivation of the pathogen in pineapple juice. In this
      respect, EfEO was chemically characterized, and its antilisteria potential in
      broth as a function of pH, cell load, and EfEO concentration was assessed through
      a central composite design. Furthermore, the inactivation kinetics of L.
      monocytogenes in the juice were assessed by combining EfEO and low pasteurization
      temperatures. A total of 81 compounds were identified from EfEO. The reduction of
      pH and cell load increased EO activity. The use of only 15 ppm of EfEO during
      pasteurization of pineapple juice at 60 degrees C reduced the time required for a
      4-log reduction in L. monocytogenes CFU/ml by 74.9% (i.e., from 8.5 to 2.1 min)
      compared with treatment without EfEO. It could be concluded that EfEO activity
      toward L. monocytogenes increases with the reduction of pH and that it can be
      used at sublethal concentrations in combination with low temperatures in
      pineapple juice pasteurization. This study demonstrates that EO-assisted
      pasteurization is a promising strategy for the reduction of thermal impact during
      juice production. EfEO is easily available and compatible with many juices and is
      thus promising for industrial application. 

PMID- 24674436
TI  - Antimicrobial mechanism and activity of dodecyl rosmarinate against
      Staphylococcus carnosus LTH1502 as influenced by addition of salt and change in
      pH.
AB  - Antimicrobial activity and mechanism of action of rosmarinic acid (RA) and
      dodecyl rosmarinate (RE12) against Staphylococcus carnosus LTH1502 were studied
      as a function of pH (5.8 to 7.2) and in the presence of salts (KCl and MgCl2, 0
      to 500 mM). Microbial cultures were exposed to unesterified RA and to esterified
      RE12, and cell number was determined by plate counting. Cells exposed to RA and
      RE12 at the minimum bactericidal concentration (200 and 0.05 mM, respectively)
      were examined using scanning electron microscopy to observe potential
      morphological changes. Activity of RA was found to be strongly dependent on pH,
      salt type, and concentration, whereas RE12 led to the compound's activity
      becoming independent of pH, salt concentration, and type. Scanning electron
      microscopy images showed that morphology of cells treated with RE12 after
      incubation of 1 h was irrevocably altered. Our results suggest that
      esterification (i) altered the mechanism of action by increasing the compound's
      affinity for cell membranes and (ii) decreased the compound's susceptibility to
      changes in environmental conditions that alter its charge. Highly specific
      changes in structure-activity relationships can be observed when esterifying a
      naturally active phenol such as RA with an alkyl chain that has a carbon chain
      length of 12. 

PMID- 24674437
TI  - Rapid detection of Listeria monocytogenes by real-time PCR in processed meat and
      dairy products.
AB  - The objectives of this study were to evaluate the detection of Listeria
      monocytogenes in different ready-to-eat foods using real-time PCR (RT-PCR).
      Various concentrations (10(0) to 10(5) CFU/ml) of L. monocytogenes ATCC 19115
      were inoculated into ham, sausage, ground meat, processed milk, cheese, and
      infant formula. L. monocytogenes ATCC 19115 in the samples was then enumerated on
      Oxford agar, and DNA was extracted from the samples before and after incubation
      at 36 degrees C for 4 h. A set of primers and hybridization probe designed in
      this study was then used to detect the pathogen. The standard curve was then
      prepared by plotting cycle threshold values for each dilution versus L.
      monocytogenes cell counts (log CFU). The specificity of the set of primers and
      hybridization probe was appropriate. A 4-h incubation at 36 degrees C before DNA
      extraction produced optimum standard curves in comparison to the results for a 0
      h incubation. Thus, a 4-h incubation at 36 degrees C was applied for monitoring
      L. monocytogenes in collected food samples. To monitor L. monocytogenes in foods,
      533 samples (ham, 129; sausage, 226; ground meat, 72; processed cheese, 54;
      processed milk, 42; and infant formula, 10) were collected from retail markets
      and from the step before pasteurization in plants. Of all 533 samples, 4 samples
      (0.8%) showed positive signals in RT-PCR. Two samples from hams (1.6%) and two
      samples from sausages (0.9%) were determined to be positive for L. monocytogenes
      at < 100 CFU/g. The results indicate that the RT-PCR detection method with the
      set of primers and hybridization probe designed in this study should be useful in
      monitoring for L. monocytogenes in processed meat and milk products. 

PMID- 24674438
TI  - Preservative effect of food-based fermentate from Lactobacillus acidophilus NX2-6
      on chilled pork patties.
AB  - The food-based fermentate (FBF) from Lactobacillus acidophilus NX2-6 has a broad
      spectrum antibacterial activity but has not previously been reported as a food
      preservative. Experiments were conducted to assess its application as a
      preservative in pork patties. The effect of freeze-dried FBF on the
      microbiological parameters, physicochemical changes, and sensory evaluations of
      chilled pork patties stored for 15 days at 4 degrees C was investigated. The five
      treatments evaluated included a control (meat only), nisin (meat plus 0.5%
      nisin), L.1 (meat plus 2% freeze-dried FBF), L.2 (meat plus 4% freeze-dried FBF),
      and L.3 (meat plus 8% freeze-dried FBF). The results showed that freeze-dried FBF
      could significantly (P < 0.05) inhibit aerobic bacteria, coliforms, Pseudomonas
      spp., and lactic acid bacteria, with the lowest microbial counts observed in L.3.
      The addition of freeze-dried FBF resulted in concentration-dependent decreases in
      total volatile basic nitrogen values and pH values but increases in lipid
      oxidation and color instability. Based on the criteria regarding microbiological
      and physicochemical parameters, the shelf life was 9 to 12 days for L.1, 12 to 15
      days for L.2, and over 15 days for L.3, while the shelf-lives of the control and
      nisin treatments were 3 to 6 days, indicating that freeze-dried FBF could extend
      the shelf life by more than 3 days. Although the shelf life of L.1 was shorter
      than those of L.2 and L.3, the appearance of L.1 was much better than those of
      L.2 and L.3. Overall, treatment with 4 or 8% freeze-dried FBF could be improved
      if color and lipid oxidation could be improved by appropriate stabilizers, and a
      lower concentration (2%) of freeze-dried FBF has great potential as a natural and
      safe preservative in chilled pork patties. 

PMID- 24674439
TI  - Postharvest strategies for deoxynivalenol and zearalenone reduction in stored
      adlay (Coix lachryma-jobi L.) grains.
AB  - Improperly practiced postharvest procedures can pose mycotoxin-related risks in
      the production of medicinal herbs. As a health food with pharmacological
      supplements, cereal-based adlay has been broadly used in oriental medical
      practice. Compared with the standard production protocol, three provisional
      critical control points (CCPs) in the conventional procedure were identified and
      assessed for mycotoxin contamination in the adlay from small farms in Korea.
      Although various mycotoxins were present, the prevalence of deoxynivalenol (DON)
      or zearalenone (ZEN) was relatively high in the adlay. In terms of drying
      conditions, field drying in the conventional pathway was associated with more
      exposure to DON than heated-air drying. Moreover, the DON or ZEN levels in chaff
      were higher than the levels in the inner grain, suggesting that the hulling
      process as another CCP would reduce the DON or ZEN exposure. In particular, the
      DON or ZEN levels in adlay stored for protracted periods without dehulling were
      very high, but a lower storage temperature of 12 degrees C was not effective at
      significantly reducing these mycotoxins. In this case, the inner grain was more
      contaminated with DON or ZEN than the chaff after protracted storage because
      surface fungi, which produce mycotoxins, can penetrate deep into grain with time.
      Heated-air drying and nonprotracted storage limited DON contamination in adlay.
      More importantly, an early dehulling process should be adopted as an easy
      preventive action to reduce the risk of exposure to DON or ZEN in adlay
      postharvest. This is monitored as a central CCP for safer production of adlay
      from local farms. 

PMID- 24674440
TI  - Acute oral safety study of sodium caseinate glycosylated via maillard reaction
      with galactose in rats.
AB  - In order to potentially use sodium caseinate (SC) glycated with galactose (Gal)
      in the food industry as a new functional ingredient with proved technological and
      biological properties, an evaluation of oral acute toxicity has been carried out.
      An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single
      oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal
      glycoconjugates were well tolerated; no adverse effects or mortality was observed
      during the 2-week observation period. No abnormal signs, behavioral changes, body
      weight changes, or alterations in food and water consumption occurred. After this
      period, no changes in hematological and serum chemistry parameters, organ
      weights, or gross pathology or histopathology were detected. It was concluded
      that SC-Gal glycoconjugates obtained via the Maillard reaction were well
      tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal
      glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose
      for male and female rats is in excess of 2,000 mg/kg of body weight. 

PMID- 24674441
TI  - Investigation of the source of residual phthalate in sundried salt.
AB  - Phthalate contamination in sundried salt has recently garnered interest in Korea.
      Phthalate concentrations were investigated in Korean sundried salts, source
      waters, and aqueous extracts from polyvinyl chloride materials used in salt
      ponds. Preliminary screening results for phthalates in Korean sundried salts
      revealed that only di(2-ethylhexyl)phthalate (DEHP) was over the limit of
      detection, with an 8.6% detection rate, and the concentration ranged from below
      the limit of detection to 0.189 mg/kg. The tolerable daily intake contribution
      ratio of the salt was calculated to be only 0.001%. Residual phthalates were
      below 0.026 mg/liter in source water, and the aqueous extracted di-n
      butylphthalate, benzylbutylphthalate, and DEHP, which are considered endocrine
      disruptors, were below 0.029 mg/kg as derived from the polyvinyl chloride
      materials in salt ponds. The transfer ratios of the six phthalates from seawater
      to sundried salts were investigated; transfer ratio was correlated with vapor
      pressure (r(2) = 0.9875). Thus, di-n-butylphthalate, benzylbutylphthalate, DEHP,
      and di-n-octylphthalate can be considered highly likely residual pollutants in
      some consumer salts. 

PMID- 24674442
TI  - Evaluation of antimicrobial resistance profiles of Salmonella isolates from
      broiler chickens at slaughter in Alberta, Canada.
AB  - Antimicrobial-resistant Salmonella species are threatening to become a serious
      public health problem. Therefore, surveillance and prudent use of antimicrobials
      is needed in both the agricultural and human health sectors. The aim of this
      study was to describe the antimicrobial susceptibility profiles of Salmonella
      isolates recovered from healthy broiler chickens at slaughter from November 2004
      to April 2005. Salmonella isolates recovered from 36 broiler flocks in Alberta,
      Canada, were serotyped and tested for antimicrobial susceptibility against 15
      antimicrobials. Of 272 Salmonella isolates tested, 64.0% were resistant to one or
      more antimicrobials, 10.0% were resistant to three or more antimicrobials, and
      1.8% were resistant to five antimicrobials. All isolates were susceptible to
      amikacin, amoxicillin-clavulanic acid, ceftiofur, cefoxitin, ceftriaxone,
      ciprofloxacin, and nalidixic acid. The highest prevalence of resistance was to
      tetracycline (54.8%), followed by streptomycin (24.2%) and sulfisoxazole (8.4%).
      The most common multiantimicrobial resistance patterns were to streptomycin
      tetracycline (24.3%), streptomycin-sulfisoxazole-tetracycline (6.6%), and
      ampicillin-streptomycin-sulfisoxazole-tetracycline (3.7%). The strongest
      associations were observed between resistance to kanamycin and tetracycline (odds
      ratio = 65.7, P = 0.001) and to ampicillin and sulfisoxazole (odds ratio = 62.9,
      P = 0.001). Salmonella Hadar and Salmonella Heidelberg were the two most common
      serovars accounting for 40.4 and 13.6% of the total isolates, respectively.
      Eighty-one percent and 12.7% of Salmonella Hadar isolates and 62.0 and 8.1% of
      Salmonella Heidelberg isolates were resistant to 1 or more and three or more
      antimicrobials, respectively. The flock level prevalence of resistance ranged
      from 5.6% for trimethoprim-sulfamethoxazole to 83.3% for tetracycline. This study
      provides baseline information on antimicrobial susceptibility of Salmonella
      isolates of broiler chickens at slaughter in Alberta that can serve as a
      benchmark for future research. 

PMID- 24674443
TI  - Sampling naturally contaminated broiler carcasses for Salmonella by three
      different methods.
AB  - Postchill neck skin maceration (NSM) and whole-carcass rinsing (WCR) are
      frequently used methods to detect salmonellae from processed broilers. These are
      practical, nondestructive methods, but they are insensitive and may result in
      false negatives (20 to 40%). Neck skin samples comprise only 4% of the skin from
      the broiler carcass by weight, while WCR will not detect firmly attached
      Salmonella organisms and only 7.5% of the rinsate is utilized. Whole-carcass
      enrichment (WCE) involves incubation of the whole carcass overnight in a
      preenrichment broth and can recover as few as 8 inoculated Salmonella cells per
      carcass. The objective of this study was to use NSM, WCR, and WCE sampling to
      detect naturally occurring Salmonella from the same commercially processed
      broiler either prechill or postchill. Ten carcasses were obtained prechill and
      another 10 postchill on each of two replicate days from each of two commercial
      processing plants. From each carcass, 8.3 g of neck skin was sampled, and then
      the carcass was rinsed with 400 ml of 1% buffered peptone water. Thirty
      milliliters was removed and incubated (WCR), and the remaining 370 ml of broth
      and the carcass were incubated at 37 degrees C for 24 h (WCE). Overall,
      Salmonella organisms were detected on 21, 24, and 32 of 40 prechill carcasses by
      NSM, WCR, and WCE, respectively, while 2, 2, and 19 of 40 postchill carcasses
      were positive by the respective methods. Prechill carcasses were 64% (77 of 120)
      positive for Salmonella, while postchill carcasses were 19% (23 of 120) positive.
      Commercial processing reduced the positive-sample prevalence by 45%. Salmonella
      organisms were detected on 20% (24 of 120) of the samples from plant 1 and 63%
      (76 of 120) of the carcasses from plant 2. This study demonstrates significant
      differences in the results for Salmonella prevalence among sampling methods both
      before and after immersion chilling, as well as between processing plants on days
      that samples were taken. 

PMID- 24674444
TI  - Cleaning conveyor belts in the chicken-cutting area of a poultry processing plant
      with 45 degrees c water.
AB  - Conveyor belts are widely used in food handling areas, especially in poultry
      processing plants. Because they are in direct contact with food and it is a
      requirement of the Brazilian health authority, conveyor belts are required to be
      continuously cleaned with hot water under pressure. The use of water in this
      procedure has been questioned based on the hypothesis that water may further
      disseminate microorganisms but not effectively reduce the organic material on the
      surface. Moreover, reducing the use of water in processing may contribute to a
      reduction in costs and emission of effluents. However, no consistent evidence in
      support of removing water during conveyor belt cleaning has been reported.
      Therefore, the objective of the present study was to compare the bacterial counts
      on conveyor belts that were or were not continuously cleaned with hot water under
      pressure. Superficial samples from conveyor belts (cleaned or not cleaned) were
      collected at three different times during operation (T1, after the preoperational
      cleaning [5 a.m.]; T2, after the first work shift [4 p.m.]; and T3, after the
      second work shift [1:30 a.m.]) in a poultry meat processing facility, and the
      samples were subjected to mesophilic and enterobacterial counts. For
      Enterobacteriaceae, no significant differences were observed between the conveyor
      belts, independent of the time of sampling or the cleaning process. No
      significant differences were observed between the counts of mesophilic bacteria
      at the distinct times of sampling on the conveyor belt that had not been
      subjected to continuous cleaning with water at 45 degrees C. When comparing
      similar periods of sampling, no significant differences were observed between the
      mesophilic counts obtained from the conveyor belts that were or were not
      subjected to continuous cleaning with water at 45 degrees C. Continuous cleaning
      with water did not significantly reduce microorganism counts, suggesting the
      possibility of discarding this procedure in chicken processing. 

PMID- 24674445
TI  - Effects of temperature and packaging types on ergosterol and Howard mold count
      values of tomato paste during storage.
AB  - The objective of the present study was to investigate the effects of temperature
      and packaging on ergosterol and Howard mold count (HMC) changes of tomato paste
      during storage. The other purpose of this study was to determine whether the
      measurement of ergosterol stability in tomato paste can be useful for the
      assessment of microbiological quality of tomato paste as related to the storage
      temperature (4, 20, 28, or 37 degrees C) and time. Ergosterol analysis was done
      by using high-performance liquid chromatography. Tomato paste samples were
      packaged in either aseptic bags or tin boxes and stored at 4, 20, 28, or 37
      degrees C for a period of 10 months. The detection limit of ergosterol was 0.1
      mg/kg. Measurements showed that packaging and storage temperatures of 28 and 37
      degrees C have a considerable influence on ergosterol and HMC changes in the
      product. The poor precision of the "percentage of discarded fruits" and HMC
      methods has increased the importance of ergosterol for the microbiological
      quality evaluation of tomato and tomato products. This article reports the data
      from what we believe to be the first survey for the influence of storage
      temperature and packaging material on ergosterol and HMC changes of tomato paste
      during storage. 

PMID- 24674446
TI  - Evaluation of heavy metals and polycyclic aromatic hydrocarbons in honeys from
      different origins.
AB  - A survey of honey samples from different geographical and botanical origins,
      including some samples collected from a fire-affected area in Spain, was
      conducted to assess their content of heavy metals and polycyclic aromatic
      hydrocarbons (PAHs). The levels of the determined toxic elements (Pb, Cd, As, and
      Sn) were low and were in the range of those reported by other studies. In our
      work the total amount of heavy metals and Pb was higher in dark honeys than in
      pale honeys. In the collected samples, no detectable levels of the 15 PAHs
      studied were found. The obtained data served to assess the levels of heavy metals
      and PAHs in honey samples from different geographical and environmental origins
      and to contribute to the scarce data about pollutant content of this matrix. In
      light of these results, the analyzed samples do not pose any serious concern to
      human health, and the data obtained in this study could serve to contribute to
      the establishment of specific maximum limits for honey. 

PMID- 24674447
TI  - Behavioral risk factors associated with listeriosis in the home: a review of
      consumer food safety studies.
AB  - Listeria monocytogenes causes human listeriosis, which is associated with the
      highest hospitalization and mortality rates of all foodborne illnesses. In recent
      years, the incidence of listeriosis has doubled in Europe, almost exclusively
      among older adults (>= 60 years of age). Food safety factors associated with
      increased risk of listeriosis include lack of adherence to "use by" dates and
      ineffective refrigerated storage of foods. Consequently, older adult consumers'
      implementation of safe food practices should be evaluated. This article is a
      review of consumer food safety cognitive and behavioral data relating to risk
      factors associated with listeriosis in the home as reported in 165 consumer food
      safety studies. Overall, only 41% of studies included assessment of consumer
      cognitive or behavioral data associated with listeriosis; of these studies 59%
      included data on safe refrigeration, 54% included data on storage time for opened
      ready-to-eat foods, and 49% included data on adherence to use-by dates. In most
      (83%) of the studies, survey-based data collection methods
      (questionnaires/interviews) were used; thus, the majority of findings were based
      on self-report (74%) and knowledge (44%). Observation (31%) and focus groups
      (12%) were less commonly used, resulting in a lack of actual behaviors and
      attitudinal data relating to listeriosis risk factors. Only 7% of studies
      included food safety data for older adults. Although older adults may fail to
      implement recommended practices, this review reveals a need for in-depth research
      to determine food safety attitudes and actual behaviors of older adults in
      conjunction with knowledge and selfreport of practices linked to increased risks
      of listeriosis. Such data combined with review findings would inform targeted
      food safety education to reduce risks associated with listeriosis in the home.

PMID- 24674448
TI  - Staying awake--a genetic region that hinders alpha2 adrenergic receptor agonist
      induced sleep.
AB  - How external stimuli prevent the onset of sleep has been little studied. This is
      usually considered to be a non-specific type of phenomenon. However, the hypnotic
      drug dexmedetomidine, an agonist at alpha2 adrenergic receptors, has unusual
      properties that make it useful for investigating this question. Dexmedetomidine
      is considered to produce an 'arousable' sleep-like state, so that patients or
      animals given dexmedetomidine become alert following modest stimulation. We
      hypothesized that it might be more difficult to make mice unconscious with
      dexmedetomidine if there was a sufficient external stimulus. Employing a
      motorized rotating cylinder, which provided a continuous and controlled arousal
      stimulus, we quantitatively measured the ability of such a stimulus to prevent
      dexmedetomidine loss of righting reflex in two inbred strains of mice (C57BL/6
      and 129X1). We found that whereas the C57BL/6 strain required a strong stimulus
      to prevent dexmedetomidine-induced hypnosis, the 129X1 strain stayed awake even
      with minimal stimuli. Remarkably, this could be calibrated as a simple threshold
      trait, i.e. a binary 'yes-no' response, which after crossing the two mouse
      strains behaved as a dominant-like trait. We carried out a genome-wide linkage
      analysis on the F2 progeny to determine if the ability of a stimulus to prevent
      dexmedetomidine hypnosis could be mapped to one or more chromosomal regions. We
      identified a locus on chromosome 4 with an associated Logarithm of Odds score
      exceeding the pre-established threshold level. These results show that complex
      traits, such as the ability of a stimulus to reverse drug-induced hypnosis, may
      have precise genetic determinants. 

PMID- 24674450
TI  - A novel echinocandin MIG0310 with anticandida activity from newly isolated
      Fusarium sp. strain MS-R1.
AB  - AIM: To isolate and identify an anticandida compound from newly isolated Fusarium
      strain MS-R1 and characterization of its activity against standard and clinical
      strains of Candida. METHODS AND RESULTS: The fungal strain, Fusarium strain MS
      R1, was isolated from soil. Molecular identification according to the internal
      transcribed spacer region of the rRNA gene sequence showed the strain to be
      strongly related to Fusarium brachygibbosum complex. Successive extractions of
      the active compound showed activity against Candida albicans, including clinical
      strains. Inhibition of a clinical strain of Candida tropicalis, but not Candida
      krusei and Candida glabrata, was also shown as tested by the broth microdilution
      assay. The compound was purified by liquid chromatography coupled with thin-layer
      chromatography and bioautography and characterized by nuclear magnetic resonance
      spectroscopy. It was confirmed to have the molecular formula C(48)H(66)O(18) and
      was identified as an echinocandin with a novel structure. CONCLUSION: A novel
      echinocandin-type antifungal metabolite, MIG0310, was isolated and characterized.
      This is a second echinocandin reported from a Fusarium species, indicating this
      genus to have wider range of echinocandin compounds. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The new compound may lead to new anticandidal drugs, broadening the
      treatment opportunities for Candida species, including those that are resistant
      to the current antifungal drugs.

PMID- 24674449
TI  - A replication study of GWAS findings in migraine identifies association in a
      Swedish case-control sample.
AB  - BACKGROUND: Migraine is a common neurovascular disorder with symptoms including
      headache of moderate to severe intensity and recurring attacks. There is no cure
      for migraine today and the pathology is poorly understood. Common forms of
      migraine have a complex genetic background and heritability has been estimated to
      be around 50%. Recent genome-wide association studies (GWAS) on European and
      American migraine cohorts have led to the identification of new genetic risk
      factors for migraine. METHODS: We performed an association study in a Swedish
      population based cohort, investigating the frequency of eight single nucleotide
      polymorphisms (SNPs) recently identified as genetic risk factors for migraine in
      three GWAS, using available array data (Illumina Omni Express chip). The eight
      SNPs were rs2651899, rs3790455, rs10166942, rs7640543, rs9349379, rs1835740,
      rs6478241 and rs11172113. Because information on rs3790455, rs10166942 and
      rs7640543 was not directly available, we selected SNPs in high Linkage
      Disequilibrium (LD) with these three SNPs, and replaced them with rs2274316,
      rs1003540 and rs4075749, respectively. RESULTS: We were able to replicate the
      association with rs2651899 and found a trend for association with rs1835740 in
      our Swedish cohort. CONCLUSIONS: This is the first reported genetic association
      study of a Swedish migraine case control material. We have thus replicated
      findings of susceptibility loci for migraine in an independent genetic material,
      thereby increasing knowledge about genetic risk factors for this common
      neurological disorder.

PMID- 24674451
TI  - A push-pull system to reduce house entry of malaria mosquitoes.
AB  - BACKGROUND: Mosquitoes are the dominant vectors of pathogens that cause
      infectious diseases such as malaria, dengue, yellow fever and filariasis. Current
      vector control strategies often rely on the use of pyrethroids against which
      mosquitoes are increasingly developing resistance. Here, a push-pull system is
      presented, that operates by the simultaneous use of repellent and attractive
      volatile odorants. METHOD/RESULTS: Experiments were carried out in a semi-field
      set-up: a traditional house which was constructed inside a screenhouse. The
      release of different repellent compounds, para-menthane-3,8-diol (PMD), catnip
      oil e.o. and delta-undecalactone, from the four corners of the house resulted in
      significant reductions of 45% to 81.5% in house entry of host-seeking malaria
      mosquitoes. The highest reductions in house entry (up to 95.5%), were achieved by
      simultaneously repelling mosquitoes from the house (push) and removing them from
      the experimental set-up using attractant-baited traps (pull). CONCLUSIONS: The
      outcome of this study suggests that a push-pull system based on attractive and
      repellent volatiles may successfully be employed to target mosquito vectors of
      human disease. Reductions in house entry of malaria vectors, of the magnitude
      that was achieved in these experiments, would likely affect malaria transmission.
      The repellents used are non-toxic and can be used safely in a human environment.
      Delta-undecalactone is a novel repellent that showed higher effectiveness than
      the established repellent PMD. These results encourage further development of the
      system for practical implementation in the field.

PMID- 24674452
TI  - Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of
      PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted
      next generation sequencing and SNP array analysis.
AB  - Myelodysplastic syndromes (MDS) are hematopoietic disorders characterized by
      ineffective hematopoiesis and progression to acute leukemia. In patients
      ineligible for hematopoietic stem cell transplantation, azacitidine is the only
      treatment shown to prolong survival. However, with the availability of a growing
      compendium of cancer biomarkers and related drugs, analysis of relevant genetic
      alterations for individual MDS patients might become part of routine evaluation.
      Therefore and in order to cover the entire bone marrow microenvironment involved
      in the pathogenesis of MDS, SNP array analysis and targeted next generation
      sequencing (tNGS) for the mostly therapy relevant 46 onco- and tumor-suppressor
      genes were performed on bone marrow biopsies from 29 MDS patients. In addition to
      the detection of mutations known to be associated with MDS in NRAS, KRAS, MPL,
      NPM1, IDH1, PTPN11, APC and MET, single nucleotide variants so far unrelated to
      MDS in STK11 (n=1), KDR (n=3), ATM (n=1) and JAK3 (n=2) were identified.
      Moreover, a recurrent microdeletion was detected in Xq26.3 (n=2), causing loss of
      PHF6 expression, a potential tumor suppressor gene, and the miR-424, which is
      involved in the development of acute myeloid leukemia. Finally, combined genetic
      aberrations affecting the VEGF/VEGFR pathway were found in the majority of cases
      demonstrating the diversity of mutations affecting different nodes of a
      particular signaling network as an intrinsic feature in MDS patients. We conclude
      that combined SNP array analyses and tNGS can identify established and novel
      therapy relevant genomic aberrations in MDS patients and track them in a clinical
      setting for individual therapy selection.

PMID- 24674453
TI  - Virtual slide telepathology with scanner systems for intraoperative frozen
      section consultation.
AB  - Telepathology provides pathology services over a distance using digital imaging
      and telecommunication for primary diagnostic practice, including intraoperative
      frozen sections. Virtual slide technology provides digitizing of histological
      slides by scanner systems and improved remote assessment substantially. In this
      retrospective study, diagnostic accuracy of intraoperative frozen sections
      assessed as virtual slide was determined. Tissue assessment was mainly requested
      for urological, gynecological and dermatological resections. Issues of time
      consumption, cost and cost effectiveness of this diagnostic method are discussed.
      1204 intraoperative frozen sections were conducted in the course of this study at
      our department over a period of 2.5 years. 98.59% of all intraoperative frozen
      sections were accurately diagnosed in the initial telepathological assessment.
      Tumor affection was present in 15.6% of frozen sections, in 174 instances already
      assessed in the initial slides (sensitivity 92.6%). Discrepant diagnoses compared
      to the final diagnosis occurred in 1.41%. Our determined averaged time for
      virtual slide technology of 10.58+/-8.19min can be ranged in well. Our study did
      not allow a full economic assessment, but some preliminary insights are pointed
      out. The quality of services is highly acceptable and the investment costs and
      the labor cost of virtual slide technology are lower than those of robotic
      microscopy.

PMID- 24674454
TI  - Multiple sporadic gastrointestinal stromal tumors concomitant with ampullary
      adenocarcinoma: a case report with KIT and PDGFRA mutational analysis and miR
      221/222 expression profile.
AB  - GISTs originating multifocally at different GI sites, in patients lacking
      familial syndromes, could be interpreted as recurrent/metastatic disease. MiR
      221/222 have recently been identified as regulators of KIT expression in GISTs.
      We report the first case of synchronous GISTs in the stomach and duodenum
      concomitant with an ampullary adenocarcinoma. Different CD117 expression patterns
      could be related to different KIT mutational status in the two lesions: gastric
      GIST showed a dot-like pattern and lacked KIT mutations; duodenal GIST had a
      strong membranous expression pattern, likely due to KIT exon 9 duplication, which
      is associated with lower response to imatinib. MiR-221/222 were downregulated in
      GISTs as compared with normal tissue (p<0.05) and expressed increased levels in
      the gastric GIST as compared with duodenal one (p<0.05). Our data support an
      independent origin of the two GISTs. Determining whether these tumors are
      multiple primaries or recurrencies is helpful to predict their malignancy and to
      select proper treatment.

PMID- 24674455
TI  - Can physical exercise or food deprivation cause release of fat-stored
      cannabinoids?
AB  - The aim of this study was to evaluate whether physical exercise or food
      deprivation may increase cannabinoid levels in serum or urine in abstinent
      chronic cannabis users. The study took place in a drug detoxification ward
      parallel to study participants receiving treatment. Six chronic, daily cannabis
      users (one female, five males, average age 30.0 years; BMI 20.8) were exposed to
      a 45-min. moderate-intensity workout and a 24-hr period of food deprivation.
      Serum samples were drawn prior to and after interventions and analysed for ?9
      tetrahydrocannabinol (THC) and 11-nor-9-carboxy-?9-tetrahydrocannabinol (THCCOOH)
      by liquid chromatography-tandem mass spectrometry (LCMSMS), and all voided urine
      was tested for THCCOOH by LCMSMS and normalized to the creatinine levels,
      yielding ng/mg ratios. There were no major differences in the measured
      cannabinoid levels in serum or urine before and after physical exercise or food
      deprivation. We conclude that exercise and/or food deprivation are unlikely to
      cause sufficient cannabinoid concentration changes to hamper correct
      interpretations in drug testing programmes. 

PMID- 24674456
TI  - Schirmer tear test I and rebound tonometry findings in healthy calves.
AB  - OBJECTIVE: To describe Schirmer tear test I and rebound tonometry findings in
      healthy bovine calves. ANIMALS STUDIED: Thirty-three clinically normal dairy
      breed calves of mean (SD) 11 (1.1) weeks (range, 9.3-13.3 weeks) of age were
      evaluated. PROCEDURES: A Schirmer tear test I was performed on each eye followed
      by tonometry, using a TonoVet((r)) without topical anesthesia. We report means
      (SD) and statistical analysis of data for each assay. RESULTS: For both Schirmer
      tear test (STT) I and tonometry, significant differences were not found between
      fellow eyes (P = 0.1536 and P = 0.83, respectively). The mean (SD) STT I value of
      all eyes was 20.4 (5.0) mm/min (range, 9-34 mm/min) while the mean (SD)
      intraocular pressure (IOP) value of all eyes was 15.2 (5.2) mmHg (range, 7-25
      mmHg). CONCLUSIONS: This study reports normal data for the STT I and rebound
      tonometry in calves. This data may be useful in complete ophthalmic examinations
      of cattle, guiding diagnosis of glaucoma, uveitis, and keratoconjunctivitis
      sicca. However, results of these diagnostic modalities must be interpreted in
      light of clinical signs, given the wide range of normal values obtained in this
      study.

PMID- 24674457
TI  - Inverted organic photovoltaic device with a new electron transport layer.
AB  - We demonstrate that there is a new solution-processed electron transport layer,
      lithium-doped zinc oxide (LZO), with high-performance inverted organic
      photovoltaic device. The device exhibits a fill factor of 68.58%, an open circuit
      voltage of 0.86 V, a short-circuit current density of -9.35 cm/mA2 along with
      5.49% power conversion efficiency. In addition, we studied the performance of
      blend ratio dependence on inverted organic photovoltaics. Our device also
      demonstrates a long stability shelf life over 4 weeks in air. 

PMID- 24674458
TI  - Aortoenteric fistula due to endojunk.

PMID- 24674460
TI  - Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and
      tissue engineering.
AB  - Hydrogels, microgels and nanogels have emerged as versatile and viable platforms
      for sustained protein release, targeted drug delivery, and tissue engineering due
      to excellent biocompatibility, a microporous structure with tunable porosity and
      pore size, and dimensions spanning from human organs, cells to viruses. In the
      past decade, remarkable advances in hydrogels, microgels and nanogels have been
      achieved with click chemistry. It is a most promising strategy to prepare gels
      with varying dimensions owing to its high reactivity, superb selectivity, and
      mild reaction conditions. In particular, the recent development of copper-free
      click chemistry such as strain-promoted azide-alkyne cycloaddition, radical
      mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click
      chemistry, and oxime reaction renders it possible to form hydrogels, microgels
      and nanogels without the use of potentially toxic catalysts or immunogenic
      enzymes that are commonly required. Notably, unlike other chemical approaches,
      click chemistry owing to its unique bioorthogonal feature does not interfere with
      encapsulated bioactives such as living cells, proteins and drugs and furthermore
      allows versatile preparation of micropatterned biomimetic hydrogels, functional
      microgels and nanogels. In this review, recent exciting developments in click
      hydrogels, microgels and nanogels, as well as their biomedical applications such
      as controlled protein and drug release, tissue engineering, and regenerative
      medicine are presented and discussed. 

PMID- 24674459
TI  - Comparative proteomic analysis of human lung telocytes with fibroblasts.
AB  - Telocytes (TCs) were recently described as interstitial cells with very long
      prolongations named telopodes (Tps; www.telocytes.com). Establishing the TC
      proteome is a priority to show that TCs are a distinct type of cells. Therefore,
      we examined the molecular aspects of lung TCs by comparison with fibroblasts
      (FBs). Proteins extracted from primary cultures of these cells were analysed by
      automated 2-dimensional nano-electrospray ionization liquid chromatography tandem
      mass spectrometry (2D Nano-ESI LC-MS/MS). Differentially expressed proteins were
      screened by two-sample t-test (P < 0.05) and fold change (>2), based on the
      bioinformatics analysis. We identified hundreds of proteins up- or down
      regulated, respectively, in TCs as compared with FBs. TC proteins with known
      identities are localized in the cytoskeleton (87%) and plasma membrane (13%),
      while FB up-regulated proteins are in the cytoskeleton (75%) and destined to
      extracellular matrix (25%). These identified proteins were classified into
      different categories based on their molecular functions and biological processes.
      While the proteins identified in TCs are mainly involved in catalytic activity
      (43%) and as structural molecular activity (25%), the proteins in FBs are
      involved in catalytic activity (24%) and in structural molecular activity,
      particularly synthesis of collagen and other extracellular matrix components
      (25%). Anyway, our data show that TCs are completely different from FBs. In
      conclusion, we report here the first extensive identification of proteins from
      TCs using a quantitative proteomics approach. Protein expression profile shows
      many up-regulated proteins e.g. myosin-14, periplakin, suggesting that TCs might
      play specific roles in mechanical sensing and mechanochemical conversion task,
      tissue homoeostasis and remodelling/renewal. Furthermore, up-regulated proteins
      matching those found in extracellular vesicles emphasize TCs roles in
      intercellular signalling and stem cell niche modulation. The novel proteins
      identified in TCs will be an important resource for further proteomic research
      and it will possibly allow biomarker identification for TCs. It also creates the
      premises for understanding the pathogenesis of some lung diseases involving TCs.

PMID- 24674461
TI  - Trigger-responsive, fast-degradable poly(beta-amino ester)s for enhanced DNA
      unpackaging and reduced toxicity.
AB  - Poly(beta-amino ester)s (PBAEs) represent an important class of cationic gene
      delivery materials which, however, suffer from uncontrolled DNA release due in
      part to the slow degradation of their polyester backbone. Additionally, PBAEs
      with high molecular weight (MW) also show considerable toxicities. In this study,
      we designed and developed PBAEs with trigger-responsive domains built-in polymer
      backbones that can be rapidly cleaved upon external UV light triggering to
      promote intracellular DNA release as well as reduce material toxicity. Photo
      responsive PBAEs were prepared via polyaddition of (2-nitro-1,3
      phenylene)bis(methylene) diacrylate and a bifunctional amine. The nitrobenzene
      moiety was placed in each repeating unit of the PBAE to allow fast response to
      external UV irradiation, and thus the ester linkers were cleaved and the polymers
      were degraded within several minutes upon UV irradiation. Cationic PBAEs with
      high MWs were able to mediate effective intracellular gene delivery, while upon
      UV irradiation post-transfection, enhanced DNA unpackaging and reduced material
      toxicity were observed, which collectively contributed to greatly improved
      transfection efficiencies in various mammalian cell types tested. This strategy
      allows precise manipulation of material toxicity and gene release profiles of
      PBAEs, and thus provides an effective design approach to address critical issues
      in non-viral gene delivery. 

PMID- 24674462
TI  - The effects of graphene nanostructures on mesenchymal stem cells.
AB  - We report the effects of two-dimensional graphene nanostructures; graphene nano
      onions (GNOs), graphene oxide nanoribbons (GONRs), and graphene oxide
      nanoplatelets (GONPs) on viability, and differentiation of human mesenchymal stem
      cells (MSCs). Cytotoxicity of GNOs, GONRs, and GONPs dispersed in distearoyl-sn
      glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG), on
      adipose derived mesenchymal stem cells (adMSCs), and bone marrow-derived
      mesenchymal stem cells (bmMSCs) was assessed by AlamarBlue and Calcein AM
      viability assays at concentrations ranging from 5 to 300 MUg/ml for 24 or 72 h.
      Cytotoxicity of the 2D graphene nanostructures was found to be dose dependent,
      not time dependent, with concentrations less than 50 MUg/ml showing no
      significant differences compared to untreated controls. Differentiation potential
      of adMSCs to adipocytes and osteoblasts, - characterized by Oil Red O staining
      and elution, alkaline phosphatase activity, calcium matrix deposition and
      Alizarin Red S staining - did not change significantly when treated with the
      three graphene nanoparticles at a low (10 MUg/ml) and high (50 MUg/ml)
      concentration for 24 h. Transmission electron microscopy (TEM) and confocal Raman
      spectroscopy indicated cellular uptake of only GNOs and GONPs. The results lay
      the foundation for the use of these nanoparticles at potentially safe doses as ex
      vivo labels for MSC-based imaging and therapy.

PMID- 24674463
TI  - Perfluorocarbon nanoemulsions with fluorescent, colloidal and magnetic
      properties.
AB  - Bimodal imaging agents that combine magnetic resonance imaging (MRI) and
      nearinfrared (NIR) imaging formulated as nanoemulsions became increasingly
      popular for imaging inflammation in vivo. Quality of in vivo imaging using
      nanoemulsions is directly dependent on their integrity and stability. Here we
      report the design of nanoemulsions for bimodal imaging, where both photostability
      and colloidal stability are equally addressed. A highly chemically and photo
      stable quaterrylenediimide dye was introduced into perfluoro-15-crown-5 ether
      (PCE) nanoemulsions. The nanoemulsions were prepared with PCE and Miglyol 812N
      mixed at 1:1 v/v ratio as internal phase stabilized by non-ionic surfactants.
      Data shows exceptional colloidal stability demonstrated as unchanged droplet size
      (~130 nm) and polydispersity (<0.15) after 182 days follow up at both 4 and 25 
      degrees C. Nanoemulsions also sustained the exposure to mechanical and
      temperature stress, and prolonged exposure to light without changes in droplet
      size, (19)F signal or fluorescence signal. No toxicity was observed in vitro in
      model inflammatory cells upon 24 h exposure while confocal microscopy showed that
      nanoemulsions droplets accumulated in the cytoplasm. Overall, our data
      demonstrates that design of bimodal imaging agents requires consideration of
      stability of each imaging component and that of the nanosystem as a whole to
      achieve excellent imaging performance.

PMID- 24674464
TI  - The role of STAT-6 as a key transcription regulator in HeLa cell death induced by
      IFN-gamma/TNF-alpha co-immobilized on nanoparticles.
AB  - Based on the fact that the transcription of STAT-1 plus its Serine 727 and
      Tyrosine 701 phosphorylation is not the pre-requisite for the cell death signal
      transduction in the IFN-gamma signaling pathway induced by co-immobilized IFN
      gamma/TNF-alpha, we investigate both in vitro and in vivo the key transcription
      regulators to promote the signal transduction of HeLa cells. It is found that IFN
      gamma R2 is the important death signal receptor in the HeLa cell death by RNA
      interference. Checking the expression of the whole transcription (STAT) protein
      family reveals that STAT-6 is highly expressed in comparison with the other STAT
      proteins. The gene silence of IFN-gamma R2 leads to the down-regulation of STAT-6
      and phosphorylation-STAT-6 (p-STAT-6) expressions. The successful gene silence of
      STAT-6 results in the reduction of HeLa cell programmed death and the expression
      of several important key factors related to programmed cell death (p53, Bcl-2,
      and Bax). More importantly, our in vivo experiments by injecting nanoparticle
      drug carriers with the co-immobilized IFN-gamma/TNF-alpha into nude mice model
      confirm the high expression of STAT-6 and p-STAT-6. It is thus concluded that, in
      response to IFN-gamma, the co-immobilized IFN-gamma/TNF-alpha unusually promotes
      the activation of STAT-6 rather than STAT-1, resulting in the enhanced cell
      programmed death in HeLa. The present work reveals the gene-level molecular
      mechanism of IFN-gamma/TNF-alpha co-immobilized on biomaterials as a potentially
      effective therapy against cancer cells.

PMID- 24674466
TI  - The biological consequences of replacing D-Ala in biphalin with amphiphilic alpha
      alkylserines.
AB  - Biphalin, a synthetic opioid peptide with a broad affinity for all opioid
      receptors (delta, MU, and kappa) and high antinociceptive activity, has been
      under extensive study as a potential analgesic drug. This study presents the
      synthesis and biological properties of four new analogues of biphalin containing
      amphiphilic alpha-alkylserines in position 2 and 2'. The incorporation of bulky
      alpha,alpha-disubstituted amino acids in the peptide chain using standard peptide
      chemistry is often unsuccessful. We synthesized depsipeptides, and then, the
      desired peptides were obtained by internal O,N-migration of the acyl residue from
      the hydroxyl to the amino group under mild basic conditions. The potency and
      selectivity of the new analogues were evaluated by a competitive receptor-binding
      assay in the rat brain using [(3)H]DAMGO (a MU ligand) and [(3)H]DELT (a delta
      ligand). Their binding affinity is strongly dependent on the chirality of alpha
      alkylserine, as analogues containing (R)-alpha-alkylserines displayed higher MU
      receptor affinity and selectivity than those incorporating the (S)-isomers.

PMID- 24674465
TI  - Osteogenic differentiation of adipose-derived stem cells and calvarial defect
      repair using baculovirus-mediated co-expression of BMP-2 and miR-148b.
AB  - Repair of large calvarial bony defect remains a challenge for orthopedic
      surgeons. Since microRNAs (miRNAs) modulate the osteogenesis of osteoprogenitor
      cells, we aimed to engineer human adipose-derived stem cells (hASCs), a promising
      cell source for bone engineering, with miRNA-expressing baculovirus vectors. We
      constructed 4 baculoviruses each expressing 1 human miRNA (miR-26a, miR-29b, miR
      148b, miR-196a) and verified that the miRNA-expressing baculovirus vectors
      augmented hASCs osteogenesis. Among these 4 miRNAs, miR-148b and miR-196a exerted
      more potent osteoinductive effects than miR-26a and miR-29b. Furthermore, we
      unveiled that co-transduction of hASCs with miR-148b-expressing and bone
      morphogenetic protein 2 (BMP-2)-expressing baculovirus vectors enhanced and
      prolonged BMP-2 expression, and synergistically promoted the in vitro osteogenic
      differentiation of hASCs. Implantation of the hASCs co-expressing BMP-2/miR-148b
      into critical-size (4 mm in diameter) calvarial bone defects in nude mice
      accelerated and potentiated the bone healing and remodeling, filling ~94% of
      defect area and ~89% of defect volume with native calvaria-like flat bone in 12
      weeks, as judged from micro computed tomography, histology and
      immunohistochemical staining. Altogether, this study confirmed the feasibility of
      combining miRNA and growth factor expression for synergistic stimulation of in
      vitro osteogenesis and in vivo calvarial bone healing.

PMID- 24674469
TI  - 4DMRI Provides More Accurate Renal Motion Estimation in IMRT in Young Children.

PMID- 24674467
TI  - Multimarker approach with cystatin C, N-terminal pro-brain natriuretic peptide, C
      reactive protein and red blood cell distribution width in risk stratification of
      patients with acute coronary syndromes.
AB  - INTRODUCTION AND AIM: Biomarkers have emerged as interesting predictors of risk
      in patients with acute coronary syndromes (ACS). The aim of this study was to
      determine the utility of the combined measurement of cystatin C (CysC), C
      reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and
      red blood cell distribution width (RDW) in the risk stratification of patients
      with ACS. METHODS: In this prospective study including 682 patients consecutively
      admitted to a coronary care unit for ACS, baseline measurements of CysC, CRP, NT
      proBNP and RDW were performed. Patients were categorized on the basis of the
      number of elevated biomarkers at presentation. The primary outcome was 6-month
      mortality. RESULTS: The number of biomarkers elevated on admission (study score)
      was an independent predictor of 6-month mortality; patients with four biomarkers
      elevated on admission had a significantly higher risk of 6-month mortality
      compared with patients with none or one. In addition, in patients with high risk
      defined by the GRACE score, our multimarker score was able to further categorize
      their risk of 6-month mortality. CONCLUSIONS: A multimarker approach using CysC,
      NT-proBNP, CRP and RDW was an independent predictor of 6-month mortality and
      added prognostic information to the GRACE risk score in patients with ACS and
      high risk defined by GRACE, with increasing mortality in patients with a higher
      number of elevated biomarkers on admission.

PMID- 24674468
TI  - Knowledge-based Organ-at-Risk Sparing Models in IMRT Planning.

PMID- 24674470
TI  - CT-Guidance Allows Interstitial Implantation in an Outpatient Setting for
      Cervical Cancer Patients.

PMID- 24674471
TI  - Absolute lymphocyte count: a novel prognostic factor for merkel cell carcinoma.

PMID- 24674472
TI  - Quantifying tumor aggressiveness using diffusion-weighted MRI for prostate
      cancer.

PMID- 24674474
TI  - Withdrawn.

PMID- 24674473
TI  - Hilgh Sensitivity and Specificity of PET/CT and Laparoscopic Diagnostic Lymph
      Node Excision for Lymph Node Metastases in Cervical Cancer Patients.

PMID- 24674475
TI  - Radiographic Changes After Lung Stereotactic Ablative Radiotherapy (SABR) -- Can
      We Distinguish Fibrosis From Recurrence? A Systematic Review of the Literature.

PMID- 24674477
TI  - Ferumoxytol as a lymph node contrast agent in patients with metastatic prostate
      carcinoma.

PMID- 24674476
TI  - Perfusion imaging in differentiating tumor recurrence from pseudoprogression in
      newly diagnosed high grade gliomas treated with bevacizumab.

PMID- 24674478
TI  - Molecular Imaging FDG-PET/CT Response to Neoadjuvant Oxaliplatin and
      Chemoradiation in Rectal Cancer as Prognostic Factor in Surveillance.

PMID- 24674479
TI  - MicroDose Digital Mammography: Lowest Dose Innovation in Breast Cancer Screening.
      Technology Review and Implications to a Screening Population.

PMID- 24674480
TI  - Imaging and pathological findings of solid pseudopapillary tumors of the
      pancreas: a report of 53 cases.

PMID- 24674482
TI  - Withdrawn.

PMID- 24674481
TI  - Selection of Patients Benefited From PET CT Whole Body Protocol.

PMID- 24674483
TI  - Preliminary Analysis of Pretreatment Diffusion-Weighted MRI and (18)F-FDG PET/CT
      as Prognostic Factors in Patients With Non-Small Cell Lung Cancer Receiving
      Stereotactic Body Radiation Therapy.

PMID- 24674484
TI  - CT Findings, Clinicopathologic Features, and Treatment Modalities of Anorectal
      Melanoma: A Report of 10 Cases.

PMID- 24674485
TI  - See oral abstract presentation #3.

PMID- 24674486
TI  - See oral abstract presentation #10.

PMID- 24674487
TI  - See oral abstract presentation #6.

PMID- 24674488
TI  - See oral abstract presentation #2.

PMID- 24674489
TI  - See oral abstract presentation #5.

PMID- 24674490
TI  - Dosimetric impact of intrafraction prostate motion using a new contour shifting
      method.

PMID- 24674492
TI  - See oral abstract presentation #1.

PMID- 24674491
TI  - Use of Implanted Gold Fiducial Markers With MV-CBCT Image Guided IMRT for
      Pancreatic Tumors.

PMID- 24674493
TI  - Clinically Significant Difference in Prostate Localization Using Daily Cone Beam
      CT (CBCT) and Electromagnetic Transponders.

PMID- 24674494
TI  - Dosimetric and clinical analysis of retreatment of vertebral body metastases
      using intensity modulated radiation therapy.

PMID- 24674495
TI  - Verification of respiratory position reproducibility with a respiration self
      monitoring device: results for 12 patients with lung tumors.

PMID- 24674496
TI  - Advanced Radiation Techniques: Stereotactic Body Radiation Therapy (SBRT) in
      Early Stage Inoperable Lung Cancer Disease.

PMID- 24674497
TI  - Optimizing Options for Re-irradiation With Deformable Image Registration of Prior
      Plans.

PMID- 24674498
TI  - SBRT Using Residual Lipiodol as Surrogate Fiducial for Image Guidance in the
      Treatment of Recurrent or Residual Hepatocellular Carcinoma.

PMID- 24674499
TI  - Early Detection of Tumor Response Using 4D DCE-CT and DCE-MRI in Patients Treated
      With Radiosurgery for Brain Metastases.

PMID- 24674500
TI  - Superiority of a real-time planning technique over image guided radiation therapy
      for the treatment of primary prostate cancers.

PMID- 24674501
TI  - Hybrid intensity modulated radiotherapy - stereotactic radiosurgery for treatment
      of pituitary macroadenomas.

PMID- 24674502
TI  - Advancing Image Guided Visualization of Cellular-based Vaccines, In Vivo, During
      Combined Radiation/Immunotherapy Protocols.

PMID- 24674503
TI  - Comparison of the Effectiveness of Radiofrequency Ablation With Stereotactic Body
      Radiation Therapy in Inoperable Stage I Non-Small Cell Lung Cancer: A Systemic
      Review and Meta-analysis.

PMID- 24674504
TI  - Selective Targeting of Brain Tumors With Nanoparticle-induced Radiosensitization
      and Contrast Enhancement.

PMID- 24674506
TI  - Hepatic Function Model Based Upon HIDA SPECT and Dose for Physiological Adaptive
      RT.

PMID- 24674505
TI  - In Vivo Verification as a Tool to Tailor Daily IGRT and Flag Adaptive
      Radiotherapy.

PMID- 24674507
TI  - Phase/Amplitude-matched Digital Tomosynthesis (DTS) Imaging for Moving Target
      Localization.

PMID- 24674508
TI  - Investigation of VMAT Algorithms and Dosimetry.

PMID- 24674509
TI  - Radiation exposure incurred by healthcare providers during radioactive seed
      localization for surgical resection of nonpalpable breast cancers.

PMID- 24674510
TI  - Implantable MRI tissue markers: design and phantom studies.

PMID- 24674511
TI  - Percutaneous CT-guided Pulmonary Fiducial Marker Placement for Small Lesions in
      High-Risk Patients: Technical Considerations, Challenges, and Complications.

PMID- 24674512
TI  - Organ Sparing Using MRI/CT Fusion for Localized Prostate Cancer.

PMID- 24674513
TI  - Withdrawn.

PMID- 24674514
TI  - FDG Pulmonary Uptake Changes During and Postradiotherapy Compared to Pretreatment
      in Predicting Radiation-induced Lung Toxicity in Non-Small Cell Lung Cancer.

PMID- 24674515
TI  - Withdrawn.

PMID- 24674516
TI  - See oral presentation #8.

PMID- 24674517
TI  - See oral presentation #12.

PMID- 24674518
TI  - Comparison of Gold Seeds, Tight Embolization Coils, and Loose Embolization Coils
      Used as Fiducial Markers for Dynamic Tracking Using CyberKnife.

PMID- 24674519
TI  - See oral presentation #7.

PMID- 24674520
TI  - Repeated monitoring of tumor oxygen while breathing carbogen to determine the
      therapeutic potential of hyperoxic therapy.

PMID- 24674521
TI  - Inter-method Comparison and Optimization of [18F] FDG PET Metabolic Response
      Assessment in Non-Small Cell Lung Cancer.

PMID- 24674522
TI  - A Pilot 11C-Choline PET-CT Imaging Study in Patients With Locally Advanced
      Esophageal Cancer.

PMID- 24674523
TI  - The Value of Positron Emission Mammography (PEM) in Management of Breast Cancer.

PMID- 24674524
TI  - Detection of Axillary Lymph Node Metastases and Extra-Axillary Metastases With
      FDG PET/CT in Breast Cancer Patients Scheduled for Neoadjuvant Chemotherapy.

PMID- 24674525
TI  - Accuracy of 3 Month Posttherapy FDG PET/CT in Resected Oral Cavity Cancer
      Patients Who Received Adjuvant Radiation.

PMID- 24674526
TI  - Predicting Outcomes in Locally-Advanced Rectal Cancer Using Pretreatment FDG-PET
      Imaging.

PMID- 24674527
TI  - A Method to Determine the Optimal Number of Bins in 4D PET.

PMID- 24674528
TI  - Understanding the Role of 18Flurodeoxyglucose PET in Predicting Improved Survival
      in Locally Advanced Pancreatic Cancer.

PMID- 24674529
TI  - Dose-related changes for lung ventilation and perfusion and prediction for
      radiation-induced lung injury during the course of radiotherapy in patients with
      non-small cell lung cancer.

PMID- 24674530
TI  - A Pilot Study of F18 EF5 PET/CT Imaging in Patients With Carcinoma of the Cervix.

PMID- 24674531
TI  - Preliminary Evaluation of Dedicated PET/MRI in Gastrointestinal Malignancy:
      Qualitative and Quantitative Comparison to PET/CT.

PMID- 24674532
TI  - A Pilot 11C-Choline PET/CT Imaging Study Investigating the Ability to Detect
      Occult Metastatic Osseous Disease in Newly Diagnosed High-Risk Prostate
      Adenocarcinoma.

PMID- 24674533
TI  - Voxelized Dose--FDG-PET Response in HDR Brachytherapy of Rectal Cancer.

PMID- 24674534
TI  - 4D PET/CT: Radiology Imaging to Radiation Therapy.

PMID- 24674535
TI  - FDG Uptake on PET/CT Can Assess Response to Chemoradiotherapy in Patients With
      Anal Cancer.

PMID- 24674536
TI  - A Translational Feline Model of Oral Squamous Cell Carcinoma for Evaluating Tumor
      Volume Delineation With PET/CT.

PMID- 24674537
TI  - Positron emission tomography texture analysis of necrosis in primary
      adenocarcinomas of the lung.

PMID- 24674538
TI  - Feasibility Study of 4D Perfusion CT for Hepatocellular Carcinoma Patients
      Treated With Radiation and Sorafenib.

PMID- 24674539
TI  - Pretreatment SUVmax as a Marker for Progression-Free Survival in Stage I NSCLC
      Treated With SBRT.

PMID- 24674540
TI  - CT Tumoral Heterogeneity as a Prognostic Marker in Primary Esophageal Cancer
      Following Neoadjuvant Chemotherapy.

PMID- 24674541
TI  - Image guided concomitant boost radiotherapy technique leads to safe dose
      escalation and improves local tumor control.

PMID- 24674542
TI  - Mapping patterns of nodal metastases in seminoma: rethinking radiotherapy fields.

PMID- 24674543
TI  - See oral presentation #4.

PMID- 24674545
TI  - Withdrawn.

PMID- 24674544
TI  - Delineation and visualization of prostate cancer in multiparametric MRI.

PMID- 24674546
TI  - Computerized Tomography-based Simulation and 3-Dimensional Radiotherapy Planning
      Improves Heterotopic Ossification Outcomes.

PMID- 24674547
TI  - MR Susceptibility-Weighted Imaging (SWI) Complements Conventional Contrast
      Enhanced Imaging for Melanoma Gamma Knife Radiosurgery Planning.

PMID- 24674548
TI  - Seminal Vesicle Target Delineation for Intermediate-Risk Prostate Cancer IMRT.

PMID- 24674549
TI  - The pattern of lymphatic metastasis and influencing factors of thoracic
      esophageal squamous cell carcinoma.

PMID- 24674550
TI  - A comparison of planning target volume definition by the patient-specific margins
      and the generic margins for thoracic esophageal cancer.

PMID- 24674551
TI  - Usefulness of Double Dose Contrast-enhanced Magnetic Resonance Imaging for Clear
      Delineation of Gross Tumor Volume in Stereotactic Radiotherapy Treatment Planning
      of Metastatic Brain Tumors: A Dose Comparison Study.

PMID- 24674552
TI  - Glioblastoma multiforme: use of clinical target volumes as possible prognostic
      factors to progression-free survival.

PMID- 24674553
TI  - The impact of computed tomography on early glottic cancer outcomes.

PMID- 24674554
TI  - Cranial Nerves Contouring Among Patients Treated With IMRT for Base of Skull,
      Nasopharyngeal, and Paranasal Sinus Cancer.

PMID- 24674555
TI  - Quantitative assessment of volumetric changes using fan beam and cone beam
      computed tomography during head and neck image guided radiotherapy.

PMID- 24674556
TI  - Dosimetric Implications of Treating 4D PET/CT-Defined Maximum Inhale Versus
      Exhale Target Volumes in Esophageal Cancer.

PMID- 24674557
TI  - Reflectance confocal microscopy in patients undergoing radiation therapy.

PMID- 24674558
TI  - Diffusion-Weighted Whole-Body Imaging With Background Body Signal Suppression
      (DWIBS) -- Application in Planning for Cyberknife Therapy in Patients With
      Gliomas.

PMID- 24674559
TI  - A Phase 2 Multi-institutional Study to Evaluate Gemcitabine and Fractionated
      Stereotactic Radiotherapy for Unresectable, Locally Advanced Pancreatic
      Adenocarcinoma.

PMID- 24674560
TI  - Correlation of Quantitative Diffusion-Weighted and Dynamic Contrast-Enhanced MRI
      Parameters With NCCN Risk Group, Gleason Score, and Maximum Tumor Diameter in
      Prostate Cancer.

PMID- 24674561
TI  - Diffusion abnormality index: a new imaging biomarker for early assessment of
      tumor response to therapy.

PMID- 24674562
TI  - Observation Versus Neck Dissection for Residual, PET-Negative Lymphadenopathy
      After Chemoradiotherapy for Head-and-Neck Cancer.

PMID- 24674563
TI  - Evaluating Effects of Radiation Therapy Treatment on 4DCT-Calculated Lung
      Ventilation.

PMID- 24674564
TI  - Renal remodeling in the first 24 months after abdominal radiotherapy.

PMID- 24674565
TI  - Deglutition-Induced Real-Time Directional Displacements in Head-and-Neck Cancer
      Patients --- Dynamic Volume Shuttle Imaging Analysis.

PMID- 24674566
TI  - Effects of Noise in 4D CT on Deformable Image Registration and Derived
      Ventilation Data.

PMID- 24674567
TI  - Deformable Imaging Capability for the Radiation Therapy Oncology Group (RTOG)
      Consensus Atlas of Musculoskeletal Anatomy (CAMAS) for Soft Tissue Sarcoma of the
      Lower Extremities.

PMID- 24674568
TI  - Characterization of Patient-Induced Geometric Distortions in Clinical Brain MRI
      on a 3T MR Simulator.

PMID- 24674569
TI  - Improving Tumor-to-Tissue CNR of 4D-MRI Using Deformable Image Registration.

PMID- 24674571
TI  - See oral abstract presentation #11.

PMID- 24674570
TI  - Cardiac and Respiratory Motion Assessment With Cine-MRI in Patients With Left
      Sided Breast Cancer.

PMID- 24674572
TI  - Anorectal angle is associated with bowel toxicity one month following radiation
      therapy for prostate cancer.

PMID- 24674574
TI  - See oral abstract presentation #9.

PMID- 24674573
TI  - Benefit of MRI scanning in the pretreatment assessment of anal canal carcinoma.

PMID- 24674575
TI  - Congenital toxoplasmosis presenting as central diabetes insipidus in an infant: a
      case report.
AB  - BACKGROUND: Congenital toxoplasmosis has a wide range of presentation at birth
      varying from severe neurological features such as hydrocephalus and
      chorioretinitis to a well appearing baby, who may develop complications late in
      infancy. While neuroendocrine abnormalities associated with congenital
      toxoplasmosis are uncommon, isolated central diabetes insipidus is extremely
      rare. CASE PRESENTATION: Here, we report on a female infant who presented with
      fever, convulsions, and polyuria. Examination revealed weight and length below
      the 3rd centile along with signs of severe dehydration. Fundal examination showed
      bilateral chorioretinitis. This infant developed hypernatremia together with
      increased serum osmolality and decreased both urine osmolality and specific
      gravity consistent with central diabetes insipidus. Serology for toxoplasma
      specific immunoglobulin M was high for both the mother and the baby and
      polymerase chain reaction for toxoplasma deoxyribonucleic acid was positive in
      the infant confirming congenital toxoplasmosis. Brain computerized tomography
      scans demonstrated ventriculomegaly associated with cerebral and cortical
      calcifications. Fluid and electrolyte abnormalities responded to nasal
      vasopressin therapy. CONCLUSION: This report highlights central diabetes inspidus
      as a rare presentation of congenital toxoplasmosis.

PMID- 24674576
TI  - The progression of myopia from its onset at age 8-12 to adulthood and the
      influence of heredity and external factors on myopic progression. A 23-year
      follow-up study.
AB  - PURPOSE: To examine myopic progression and factors connected with myopic
      progression. METHODS: Myopic schoolchildren, with no previous spectacles, 119
      boys and 121 girls, were recruited during 1983-1984 to a randomized 3-year
      clinical trial of bifocal treatment of myopia with a subsequent 20-year follow
      up. Participants' mean age at Baseline was 10.9, ranging from 8.7 to 12.8 years.
      An ophthalmological examination was carried out annually for 3 years and twice
      thereafter at ca. 10-year intervals. Additional refraction values were received
      from prescriptions issued by different ophthalmologists and opticians.
      Altogether, 1915 refraction values were available. Reading distance and
      accommodation were measured at each control visit. Data on parents' myopia, daily
      time spent on reading and close work, outdoor activities and watching television
      were gathered with a structured questionnaire. RESULTS: Using bifocals (+1.75
      add) or reading without glasses or accommodation stimulus during the 3-year
      period in childhood did not correlate with adulthood refraction. Short reading
      distance in childhood predicted higher adulthood myopia among females. The
      factors predicting faster myopic progression were parents' myopia and less time
      spent on sports and outdoor activities at childhood. Time spent on reading and
      close work in childhood was related to myopic progression during the first 3
      years but did not predict adulthood myopia. Myopia throughout follow-up was
      higher among those who watched television <3 hr daily than those who spent more
      time watching television. Mean myopic progression 8 years after age 20-24 was 
      0.45 D +/- 0.71 (SD), and in 45% of cases, progression was >=0.5 D. CONCLUSIONS:
      In nearly half of the cases, myopia beginning at school continued to progress
      into adulthood. Higher adulthood myopia was mainly related to parents' myopia and
      less time spent on sports and outdoor activities in childhood.

PMID- 24674577
TI  - Pretreatment with clonidine caused desensitization to WIN 55,212-2 in guinea pig
      ileum.
AB  - Considering the existence of cross-tolerance between clonidine and morphine
      besides the same interaction between morphine and WIN 55,212-2 persuaded us to
      verify this fact between WIN 55,212-2 and clonidine in guinea pig ileum, which is
      a well-known model to examine the mode of action of cannabinoids and alpha2 
      adenoceptor agonists The rectangular pulses were passed to the 0.5 g stretched
      ileum segments that were fixed in 20-ml organ bath. PowerLab system and Graphpad
      Prism were applied to record twitches and analyse the data. Electrically evoked
      contractions were dose-dependently inhibited by WIN 55,212-2 and clonidine (pD2 =
      8.56 +/- 0.41 and 7.65 +/- 0.15, respectively). Tolerance to this effect could be
      induced by 4-h incubation with WIN 55,212-2 (3 * IC50 ) (pD2  = 6.36 +/- 0.26,
      degree of tolerance: 159.32) (P < 0.01) but not with clonidine (2 * IC50 and 4 *
      IC50 ) for different time courses. Dose-response curve for inhibitory action of
      WIN 55,212-2 was shifted to the right after 4-h incubation with clonidine (3 *
      10(-10) m) comparing to the untreated tissues (pD2  = 5.26 +/- 0.69, degree of
      tolerance: 2000) (P < 0.001). This observation provides the evidence for the
      cannabinoid-noradrenergic systems interaction in the enteric nervous system as a
      simplified representative for central nervous system. 

PMID- 24674579
TI  - Awareness and attitude to the law banning smoking in public places in Osun State,
      Nigeria.
AB  - OBJECTIVE: This study determined the awareness and attitude towards the Osun
      state prohibition of smoking in public places law. METHOD: Descriptive cross
      sectional study design. 520 consenting respondents recruited using a convenience
      sampling method were interviewed using a semi-structured questionnaire covering
      their smoking pattern, awareness and attitude towards the law of prohibition of
      smoking in public places in Osun State. Data analyzed using descriptive and chi
      square statistics. RESULTS: Only 38% were aware of the law while none had seen
      the document. Fifty six percent felt cigarette smoking is a problem that required
      the law to be implemented, while only 20% agreed that the law will stop tobacco
      use. The radio (58%), bill boards (45%) and newspapers (44%) were the major
      sources of awareness of the law. The perception of risk posed to the public and
      family health by cigarette smoking was poor among the participants. CONCLUSION:
      There is poor awareness and attitude to the law of prohibition of smoking in
      public places in Osun State. It is necessary to increase sensitization of the
      general public and enforcement of the law.

PMID- 24674578
TI  - GABAergic transmission in rat pontine reticular formation regulates the induction
      phase of anesthesia and modulates hyperalgesia caused by sleep deprivation.
AB  - The oral part of the pontine reticular formation (PnO) contributes to the
      regulation of sleep, anesthesia and pain. The role of PnO gamma-aminobutyric acid
      (GABA) in modulating these states remains incompletely understood. The present
      study used time to loss and time to resumption of righting response (LoRR and
      RoRR) as surrogate measures of loss and resumption of consciousness. This study
      tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat
      PnO alters LoRR, RoRR and nociception; (ii) propofol decreases GABA levels in the
      PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by
      sleep deprivation. Administering a GABA synthesis inhibitor [3-mercaptopropionic
      acid (3-MPA)] or a GABA uptake inhibitor [nipecotic acid (NPA)] into rat PnO
      significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR
      for propofol (-18%). NPA significantly increased LoRR during administration of
      propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of
      propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and
      increased by NPA is consistent with measures showing that extracellular GABA
      levels in the PnO were decreased (41%) by propofol. Thermal nociception was
      significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the
      hyperalgesia caused by sleep deprivation. The results demonstrate that GABA
      levels in the PnO regulate the time for loss of consciousness caused by propofol,
      extend the concept that anesthetic induction and emergence are not inverse
      processes, and suggest that GABAergic transmission in the PnO mediates
      hyperalgesia caused by sleep loss. 

PMID- 24674580
TI  - Preservation of the internal vesical sphincter and proximal urethra during
      retropubic radical prostatectomy may improve earlier recovery of continence in
      selected patients.
AB  - OBJECTIVES: To evaluate the influence of preservation of the muscular internal
      sphincter and proximal urethra on continence recovery after radical prostatectomy
      (RP). MATERIAL AND METHODS: Fifty-five consecutive patients with organ confined
      prostate cancer were submitted to RP with the preservation of muscular internal
      sphincter and the proximal urethra (group 1) and compared to 55 patients
      submitted to standard procedure (group 2). Continence rates were assessed using a
      self-administrated questionnaire at 3, 7, 30 days and 3, 12 months after removal
      of the catheter. RESULTS: Group 1 had a faster recovery of continence than group
      2 at 3 days (50.9% vs. 25.5%; P=.005), at 7 days (78.2% vs. 58.2%; P=.020), at 30
      days (80.0% vs. 61.8%; P=.029) and at 3 months (81.8% vs. 61.8%; P=.017); there
      were no statistically difference in terms of continence at 12 months among the
      two groups. Multivariate logistic regression analysis of continence showed that
      surgical technique was significantly associated with earlier time to continence
      at 3 and 7 days. The two groups had no significant differences in terms of
      surgical margins. CONCLUSIONS: Our modified technique of RP with preservation of
      smooth muscular internal sphincter as well as of the proximal urethra during
      bladder neck dissection resulted in significant increased early urinary
      continence at 3, 7, 30 days and 3 months after catheter removal. The technique
      does not increase the rate of positive margins and the duration of the procedure.

PMID- 24674581
TI  - The AALAS journals: 2013 in review.

PMID- 24674583
TI  - Urinary MCP1 and Microalbumin increase prior to onset of Azotemia in mice with
      polycystic kidney disease.
AB  - Urinary biomarkers may offer a more sensitive and less invasive means to monitor
      kidney disease than traditional blood chemistry biomarkers such as creatinine.
      CD1(pcy/pcy) (pcy) mice have a slowly progressive disease phenotype that
      resembles human autosomal dominant polycystic kidney disease with renal cyst
      formation and inflammation. Previous reports suggest that dietary protein
      restriction may slow disease progression in mice and humans with polycystic
      kidney disease. Accordingly, we fed pcy mice either a standard chow (22.5%
      protein) or a protein-restricted (11.5% soy-based protein) diet from weaning
      until 34 wk of age. Every 6 wk we measured markers of kidney disease, including
      serum creatinine, BUN, and serum albumin as well as urinary monocyte
      chemoattractant protein 1 (MCP1), microalbumin, and specific gravity. Progression
      of kidney disease was equivalent for both diet groups despite dietary protein
      restriction. Urinary biomarkers proved useful for early detection of disease, in
      that urinary microalbumin was elevated as early as 22 wk of age and urinary MCP1
      was increased by 28 wk of age, whereas increases in serum creatinine and BUN were
      detected later (at 34 wk of age) in both diet groups. Thus, urinary microalbumin
      and MCP1 analyses provided earlier, noninvasive indicators for detection of
      kidney disease and disease progression in pcy mice than did serum creatinine and
      BUN. 

PMID- 24674582
TI  - Segmented filamentous bacteria: commensal microbes with potential effects on
      research.
AB  - Segmented filamentous bacteria (SFB) are commensal bacteria that were first
      identified in the ilea of mice and rats. Morphologically similar bacteria occur
      in a broad range of host species, but all strains have been refractory to in
      vitro culture thus far. Although SFB were once considered innocuous members of
      the intestinal microbiota of laboratory rodents, they are now known to affect the
      development of the immune system in rodents and, subsequently, the phenotype of
      models of both enteric and extraintestinal disease. Therefore, SFB represent long
      recognized commensal bacteria serving as an intercurrent variable in studies
      using rodent models of disease. Here we describe the basic biology of SFB and
      discuss the immunologic and physiologic effects of colonization with SFB, with
      particular attention to their effects on rodent models of disease. In addition,
      we propose that SFB represent only the 'tip of the iceberg' in our understanding
      of the influence of the microbiota on model phenotypes. As next-generation
      sequencing techniques are increasingly used to investigate organisms that are
      refractory to culture, we are likely to identify other commensal microbes that
      alter the models we use. This review underscores the need to characterize such
      host-microbe interactions, given that animal research represents a critical tool
      that is particularly vulnerable to scrutiny in an era of decreasing financial
      resources and increasing accountability for the use of animal models. 

PMID- 24674584
TI  - Dietary repletion with omega3 fatty acid or with COX inhibition reverses
      cognitive effects in F3 omega3 fatty-acid-deficient mice.
AB  - Dietary deficiency of omega3 fatty acid during development leads to impaired
      cognitive function. However, the effects of multiple generations of omega3 fatty
      acid deficiency on cognitive impairment remain unclear. In addition, we sought to
      test the hypothesis that the cognitive impairments of omega3 fatty-acid-deficient
      mice are mediated through the arachidonic acid-cyclooxygenase (COX) pathway. To
      address these issues, C57BL/6J mice were bred for 3 generations and fed diets
      either deficient (DEF) or sufficient (SUF) in omega3 fatty acids. At postnatal
      day 21, the F3 offspring remained on the dam's diet or were switched to the
      opposite diet, creating 4 groups. In addition, 2 groups that remained on the
      dam's diet were treated with a COX inhibitor. At 19 wk of age, spatial
      recognition memory was tested on a Y-maze. Results showed that 16 wk of SUF diet
      reversed the cognitive impairment of F3 DEF mice. However, 16 wk of omega3 fatty
      acid-deficient diet impaired the cognitive performance of the F3 SUF mice, which
      did not differ from that of the F3 DEF mice. These findings suggest that the
      cognitive deficits after multigenerational maintenance on omega3 fatty-acid
      deficient diet are not any greater than are those after deficiency during a
      single generation. In addition, treatment with a COX inhibitor prevented spatial
      recognition deficits in F3 DEF mice. Therefore, cognitive impairment due to
      dietary omega3 fatty-acid deficiency appears to be mediated by the arachidonic
      acid-COX pathway and can be prevented by 16 wk of dietary repletion with omega3
      fatty acids or COX inhibition. 

PMID- 24674585
TI  - Bacterial infections in Myd88-deficient mice.
AB  - Three breeding colonies of Myd88(-/-) mice had a history of significant morbidity
      and mortality. Although strain-specific poor reproductive performance might
      explain neonatal death and dystocia, mice were found dead or required euthanasia
      because of moribundity, distended abdomen, head tilt, and seizures.
      Histopathology results included bacteremia, placentitis, metritis, peritonitis
      with abscess formation, and suppurative meningoencephalitis. Intralesional gram
      negative coccobacilli were present, often in extremely high number. Cultures of
      samples of the cardiac blood of a mouse and from water-bottle sipper tubes
      provided to some affected mice grew Pseudomonas aeruginosa. In addition, affected
      tissues from 2 mice and feces from a third tested PCR-positive for P. aeruginosa.
      Although the mice had received autoclaved reverse-osmosis-purified drinking
      water, we suspect that the mice were inoculated with P. aeruginosa through
      contaminated sipper tubes. Because of the deficiency in most of the Toll-like
      receptor signaling pathways, these Myd88(-/-) mice were unlikely to have
      developed competitive innate and adaptive immune responses, resulting in
      bacterial infections. These clinical cases underscore the importance of
      understanding how genotype, phenotype and environment affect animal health. Sound
      husbandry and experimental practices are needed to prevent the exposure of immuno
      deficient mice to pathogens. 

PMID- 24674586
TI  - Case study: polycystic livers in a transgenic mouse line.
AB  - Three mice (2 male, 1 female; age, 5 to 16 mo) from a mouse line transgenic for
      keratin 14 (K14)-driven LacZ expression and on an outbred Crl:CD1(ICR)
      background, were identified as having distended abdomens and livers that were
      diffusely enlarged by numerous cysts (diameter, 0.1 to 2.0 cm). Histopathology
      revealed hepatic cysts lined by biliary type epithelium and mild chronic
      inflammation, and confirmed the absence of parasites. Among 21 related mice, 5
      additional affected mice were identified via laparotomy. Breeding of these 5 mice
      (after 5 mo of age) did not result in any offspring; the K14 mice with polycystic
      livers failed to reproduce. Affected male mice had degenerative testicular
      lesions, and their sperm was immotile. Nonpolycystic K14 control male mice bred
      well, had no testicular lesions, and had appropriate sperm motility. Genetic
      analysis did not identify an association of this phenotype with the transgene or
      insertion site. 

PMID- 24674587
TI  - Prophylactic effects of the glucagon-like Peptide-1 analog liraglutide on
      hyperglycemia in a rat model of type 2 diabetes mellitus associated with chronic
      pancreatitis and obesity.
AB  - The objective of this study was to investigate the effects of liraglutide, an
      analog of human glucagon-like peptide 1 (GLP1), on WBN/Kob-Lepr(fa) (fa/fa) rats,
      which spontaneously develop type 2 diabetes mellitus with pancreatic disorder and
      obesity. Male fa/fa rats (age, 7 wk) were allocated into 4 groups and received
      liraglutide (37.5, 75, 150 MUg/kg SC) or saline (control group) once daily for 4
      wk. All rats in the control group became overweight and developed hyperglycemia
      as they aged. Although the rats given liraglutide showed a dose-dependent
      reduction in food intake, no significant effects on body weight or fat content
      occurred. In the liraglutide groups, the development of hyperglycemia was
      suppressed, even as plasma insulin concentrations increased in a dose-dependent
      manner. Intravenous glucose tolerance testing of the liraglutide-treated rats
      confirmed improvement of glucose tolerance and enhanced insulin secretion.
      Histologic examination revealed increased numbers of pancreatic beta-cell type
      islet cells and increased proliferation of epithelial cells of the small ducts in
      the liraglutide-treated groups. Although our study did not reveal a significant
      decrease in obesity after liraglutide administration, the results suggest a
      marked antidiabetic effect characterized by increased insulin secretion in fa/fa
      rats with pancreatic disorders. 

PMID- 24674588
TI  - A simple, quantitative method using alginate gel to determine rat colonic tumor
      volume in vivo.
AB  - Many studies of the response of colonic tumors to therapeutics use tumor
      multiplicity as the endpoint to determine the effectiveness of the agent. These
      studies can be greatly enhanced by accurate measurements of tumor volume. Here we
      present a quantitative method to easily and accurately determine colonic tumor
      volume. This approach uses a biocompatible alginate to create a negative mold of
      a tumor-bearing colon; this mold is then used to make positive casts of dental
      stone that replicate the shape of each original tumor. The weight of the dental
      stone cast correlates highly with the weight of the dissected tumors. After
      refinement of the technique, overall error in tumor volume was 16.9% +/- 7.9% and
      includes error from both the alginate and dental stone procedures. Because this
      technique is limited to molding of tumors in the colon, we utilized the
      Apc(Pirc/+) rat, which has a propensity for developing colonic tumors that
      reflect the location of the majority of human intestinal tumors. We have
      successfully used the described method to determine tumor volumes ranging from 4
      to 196 mm3. Alginate molding combined with dental stone casting is a facile
      method for determining tumor volume in vivo without costly equipment or knowledge
      of analytic software. This broadly accessible method creates the opportunity to
      objectively study colonic tumors over time in living animals in conjunction with
      other experiments and without transferring animals from the facility where they
      are maintained.

PMID- 24674589
TI  - Craniofacial trauma as a clinical marker of seizures in a baboon colony.
AB  - Baboons provide a natural model of epilepsy. However, spontaneous seizures are
      usually sporadic, brief, and may not be observed. We hypothesized that various
      types of craniofacial trauma (CFT) may serve as reliable markers for epilepsy. We
      evaluated the type, demographics, and clinical significance of CFT in a large
      baboon colony. CFT was categorized according to somatotopic location, propensity
      to recur, and association with witnessed seizures or abnormal EEG findings. We
      divided the baboons with CFT into 2 groups: those with known histories of
      seizures (CFT+Sz, n = 176) and those without seizure histories (CFTonly; n =
      515). In CFT+Sz baboons, the 568 injuries identified included periorbital (57%),
      scalp (27%), muzzle (12%), and facial (4%) injuries; multiple somatotopic
      locations or body parts were affected in 21 baboons. The most common CFT injuries
      associated with seizures were periorbital and scalp lesions (43% for each
      region). Compared with those in CFTonly animals, EEG abnormalities, including
      interictal epileptic discharges (IED) and photosensitivity were more prevalent in
      the CFT+Sz group, particularly among baboons with periorbital or scalp injuries.
      Compared with CFT+Sz animals, CFTonly baboons tended to have later onset and less
      frequent recurrence of CFT but higher prevalence of muzzle and tooth injuries.
      IED and photosensitivity were less prevalent in the CFTonly than the CFT+Sz
      group, with periorbital injuries carrying the highest and muzzle injuries the
      lowest association with IED or photosensitivity in both groups. Therefore, CFT in
      general and periorbital injuries in particular may be markers for seizures in
      baboons. 

PMID- 24674590
TI  - Role of retinoic acid and fibroblast growth factor 2 in neural differentiation
      from cynomolgus monkey (Macaca fascicularis) embryonic stem cells.
AB  - Retinoic acid is a widely used factor in both mouse and human embryonic stem
      cells. It suppresses differentiation to mesoderm and enhances differentiation to
      ectoderm. Fibroblast growth factor 2 (FGF2) is widely used to induce
      differentiation to neurons in mice, yet in primates, including humans, it
      maintains embryonic stem cells in the undifferentiated state. In this study, we
      established an FGF2 low-dose-dependent embryonic stem cell line from cynomolgus
      monkeys and then analyzed neural differentiation in cultures supplemented with
      retinoic acid and FGF2. When only retinoic acid was added to culture, neurons
      differentiated from FGF2 low-dose-dependent embryonic stem cells. When both
      retinoic acid and FGF2 were added, neurons and astrocytes differentiated from the
      same embryonic stem cell line. Thus, retinoic acid promotes the differentiation
      from embryonic stem cells to neuroectoderm. Although FGF2 seems to promote self
      renewal in stem cells, its effects on the differentiation of stem cells are
      influenced by the presence or absence of supplemental retinoic acid. 

PMID- 24674591
TI  - Endometrial decidualization and deciduosis in aged rhesus macaques (Macaca
      mulatta).
AB  - Superficial decidualization of the endometrial stroma is an essential feature of
      the implantation stage of pregnancy in rhesus macaques and other primates.
      Decidualization involves proliferation of the endometrial stromal cells, with
      differentiation into morphologically distinct decidual cells. Previous reports
      involving nonpregnant rhesus monkeys have described local- ized and widespread
      endometrial decidualization in response to administration of progesterone and
      synthetic progestogens. Ectopic decidua or 'deciduosis' describes the condition
      in which groups of decidual cells are located outside of the endometrium, most
      often in the ovaries, uterus and cervix but also in various other organs. In
      humans, most cases of deciduosis are associated with normal pregnancy, and
      ectopic decidua can be found in the ovary in nearly all term pregnancies. Here we
      describe pronounced endometrial decidualization in 2 rhesus macaques. Both
      macaques had been treated long-term with medroxyprogesterone acetate for presumed
      endometriosis, which was confirmed in one of the macaques at postmortem
      examination. In one animal, florid extrauterine and peritoneal serosal
      decidualization was admixed multifocally with carcinomatosis from a primary
      colonic adenocarcinoma. Cells constituting endometrial and serosal
      decidualization reactions were immunopositive for the stromal markers CD10,
      collagen IV, smooth muscle actin, and vimentin and immunonegative for
      cytokeratin. In contrast, carcinomatous foci were cytokeratin-positive. To our
      knowledge, this report describes the first cases of serosal peritoneal
      decidualization in rhesus macaques. The concurrent presentation of serosal
      peritoneal decidualization with carcinomatosis is unique. 

PMID- 24674592
TI  - Genome-wide association studies for hematological traits in Chinese Sutai pigs.
AB  - BACKGROUND: It has been shown that hematological traits are strongly associated
      with the metabolism and the immune system in domestic pig. However, little is
      known about the genetic architecture of hematological traits. To identify
      quantitative trait loci (QTL) controlling hematological traits, we performed
      single marker Genome-wide association studies (GWAS) and haplotype analysis for
      15 hematological traits in 495 Chinese Sutai pigs. RESULTS: We identified 161
      significant SNPs including 44 genome-wide significant SNPs associated with 11
      hematological traits by single marker GWAS. Most of them were located on SSC2.
      Meanwhile, we detected 499 significant SNPs containing 154 genome-wide
      significant SNPs associated with 9 hematological traits by haplotype analysis.
      Most of the identified loci were located on SSC7 and SSC9. CONCLUSIONS: We
      detected 4 SNPs with pleiotropic effects on SSC2 by single marker GWAS and (or)
      on SSC7 by haplotype analysis. Furthermore, through checking the gene functional
      annotations, positions and their expression variation, we finally selected 7
      genes as potential candidates. Specially, we found that three genes (TRIM58,
      TRIM26 and TRIM21) of them originated from the same gene family and executed
      similar function of innate and adaptive immune. The findings will contribute to
      dissection the immune gene network, further identification of causative mutations
      underlying the identified QTLs and providing insights into the molecular basis of
      hematological trait in domestic pig.

PMID- 24674593
TI  - Characterization of a lamotrigine-resistant kindled model of epilepsy in mice:
      evaluation of drug resistance mechanisms.
AB  - The aims of this study were to characterize a lamotrigine-resistant kindled model
      of epilepsy in mice, to study the anticonvulsant effect of carbamazepine (CBZ)
      and valproic acid (VPA), and to probe into the mechanism for resistance. Swiss
      albino mice were kindled by a subconvulsive dose of pentylenetetrazole (PTZ, 30
      mg/kg, i.p., every other day for 6 weeks). The mice were pre-treated (30 min.)
      either with a low dose of LTG (5 mg/kg, i.p.) or with vehicle, and the seizures
      were scored. The acute treatment with LTG (15 mg/kg, i.p.) on the last day
      blocked seizure in the vehicle-treated group, but the LTG pre-treated group
      showed resistance. This resistance was extended to CBZ, but not to VPA. The
      resistant model was successfully replicated in mice with less kindling
      development time (6 weeks versus 9 weeks 5 days in rats). A highly significant
      decrease in the level of histamine (p < 0.001) was found, and there were also
      decreases in serotonin, GABA and AChE levels (p < 0.05). A significantly low
      level of histamine correlates with drug resistance and indicates involvement of
      the H1/H3 receptors. It is suggested that the selective action on voltage-gated
      Na(+) and Ca(2+) channels could explain the differences in the sensitivity of CBZ
      and VPA. 

PMID- 24674595
TI  - Investigation into in vitro and in vivo models using intestinal epithelial IPEC
      J2 cells and Caenorhabditis elegans for selecting probiotic candidates to control
      porcine enterotoxigenic Escherichia coli.
AB  - AIMS: To identify a fast, economic and reliable method for preselecting lactic
      acid-producing bacterial (LAB) isolates to control enterotoxigenic Escherichia
      coli (ETEC). METHODS AND RESULTS: Two assays with porcine intestinal epithelial
      IPEC-J2 cells or Caenorhabditis elegans for selecting effective probiotic
      candidates were compared. Both assays were based on measuring death of cells or
      worms caused by ETEC strain JG280. Six of 13 LAB isolates showed >=50% protection
      in each assay, among which only four isolates (>=50% protection) were
      consistently selected by both assays. Isolate CL9 (Lactobacillus reuteri) was
      further studied. It reduced gene expression of estA, estB and elt in JG280 in
      both assays. Furthermore, the isolate protected IPEC-J2 and C. elegans from cell
      and worm death caused by STa, STb or LT enterotoxin expressed in E. coli
      DH5alpha. CL9 also promoted host defensive responses by decreasing IL-8 and
      increasing IL-10 production in IPEC-J2 cells and expression of antimicrobial
      peptide genes clec-60, clec-85 in C. elegans. CONCLUSIONS: Caenorhabditis elegans
      is useful for preselecting probiotic candidates to control ETEC after initial
      screening with IPEC-J2 cells. SIGNIFICANCE AND IMPACT OF THE STUDY: A combination
      of IPEC-J2 cell and C. elegans assays can improve the effectiveness in
      preselecting probiotic candidates.

PMID- 24674596
TI  - The metabolic flux phenotype of heterotrophic Arabidopsis cells reveals a
      flexible balance between the cytosolic and plastidic contributions to
      carbohydrate oxidation in response to phosphate limitation.
AB  - Understanding the mechanisms that allow plants to respond to variable and reduced
      availability of inorganic phosphate is of increasing agricultural importance
      because of the continuing depletion of the rock phosphate reserves that are used
      to combat inadequate phosphate levels in the soil. Changes in gene expression,
      protein levels, enzyme activities and metabolite levels all point to a
      reconfiguration of the central metabolic network in response to reduced
      availability of inorganic phosphate, but the metabolic significance of these
      changes can only be assessed in terms of the fluxes supported by the network.
      Steady-state metabolic flux analysis was used to define the metabolic phenotype
      of a heterotrophic Arabidopsis thaliana cell culture grown on a Murashige and
      Skoog medium containing 0, 1.25 or 5 mm inorganic phosphate. Fluxes through the
      central metabolic network were deduced from the redistribution of (13) C into
      metabolic intermediates and end products when cells were labelled with [1-(13)
      C], [2-(13) C], or [(13) C6 ]glucose, in combination with (14) C measurements of
      the rates of biomass accumulation. Analysis of the flux maps showed that reduced
      levels of phosphate in the growth medium stimulated flux through
      phosphoenolpyruvate carboxylase and malic enzyme, altered the balance between
      cytosolic and plastidic carbohydrate oxidation in favour of the plastid, and
      increased cell maintenance costs. We argue that plant cells respond to phosphate
      deprivation by reconfiguring the flux distribution through the pathways of
      carbohydrate oxidation to take advantage of better phosphate homeostasis in the
      plastid. 

PMID- 24674594
TI  - Protocol for a randomized comparison of integrated versus consecutive dual task
      practice in Parkinson's disease: the DUALITY trial.
AB  - BACKGROUND: Multiple tasking is an integral part of daily mobility. Patients with
      Parkinson's disease have dual tasking difficulties due to their combined motor
      and cognitive deficits. Two contrasting physiotherapy interventions have been
      proposed to alleviate dual tasking difficulties: either to discourage
      simultaneous execution of dual tasks (consecutive training); or to practice their
      concurrent use (integrated training). It is currently unclear which of these
      training methods should be adopted to achieve safe and consolidated dual task
      performance in daily life. Therefore, the proposed randomized controlled trial
      will compare the effects of integrated versus consecutive training of dual
      tasking (tested by combining walking with cognitive exercises). METHODS AND
      DESIGN: Hundred and twenty patients with Parkinson's disease will be recruited to
      participate in this multi-centered, single blind, randomized controlled trial.
      Patients in Hoehn & Yahr stage II-III, with or without freezing of gait, and who
      report dual task difficulties will be included. All patients will undergo a six
      week control period without intervention after which they will be randomized to
      integrated or consecutive task practice. Training will consist of standardized
      walking and cognitive exercises delivered at home four times a week during six
      weeks. Treatment is guided by a physiotherapist twice a week and consists of two
      sessions of self-practice using an MP3 player. Blinded testers will assess
      patients before and after the control period, after the intervention period and
      after a 12-week follow-up period. The primary outcome measure is dual task gait
      velocity, i.e. walking combined with a novel untrained cognitive task to evaluate
      the consolidation of learning. Secondary outcomes include several single and dual
      task gait and cognitive measures, functional outcomes and a quality of life
      scale. Falling will be recorded as a possible adverse event using a weekly phone
      call for the entire study period. DISCUSSION: This randomized study will evaluate
      the effectiveness and safety of integrated versus consecutive task training in
      patients with Parkinson's disease. The study will also highlight whether dual
      task gait training leads to robust motor learning effects, and whether these can
      be retained and carried-over to untrained dual tasks and functional mobility.
      TRIAL REGISTRATION: Clinicaltrials.gov NCT01375413.

PMID- 24674597
TI  - AST Cutting Edge of Transplantation 2013 Meeting Report: a comprehensive look at
      B cells and antibodies in transplantation.
AB  - Antibody-mediated rejection (ABMR) represents a significant clinical challenge
      for solid organ transplantation. Mechanistic understanding of ABMR is incomplete
      and diagnostic accuracy for ABMR is limited, and as a result, targeted treatment
      remains elusive and new treatment modalities are difficult to validate. Three
      hundred twenty-six participants from 15 countries met for the first Cutting Edge
      of Transplantation (CEOT) symposium organized by the American Society of
      Transplantation (AST) in Chandler, Arizona, February 14-16, 2013. During the 3
      day interactive symposium, presentations, moderated poster sessions and round
      table discussions addressed cutting edge knowledge of B and plasma cell biology,
      mechanisms of antibody-mediated tissue injury, advances and limitations in ABMR
      diagnostics, as well as current and potential new treatment options for ABMR. The
      outcome of the meeting identified the following unmet needs for: (a) improved
      understanding of the regulation of B cell maturation and antibody response to
      enable targeted therapies; (b) more precise diagnostics of ABMR, including
      molecular pathology, risk stratification by sensitive antibody testing and
      monitoring of treatment effects; and (c) innovative multicenter trial designs
      that enhance observational power, in particular, in assessing synergistic
      multimodality therapies with reduced toxicities. 

PMID- 24674598
TI  - Numerical simulations of the blood flow in the patient-specific arterial cerebral
      circle region.
AB  - The Cerebral Circle Region, also known as the Circle of Willis (CoW), is a loop
      of arteries that form arterial connections between supply arteries to distribute
      blood throughout the cerebral mass. Among the population, only 25% to 50% have a
      complete system of arteries forming the CoW. 3D time-varying simulations for
      three different patient-specific artery anatomies of CoW were performed in order
      to gain a better insight into the phenomena existing in the cerebral blood flow.
      The models reconstructed on the basis of computer tomography images start from
      the aorta and include the largest arteries that supply the CoW and the arteries
      of CoW. Velocity values measured during the ultrasound examination have been
      compared with the results of simulations. It is shown that the flow in the right
      anterior artery in some cases may be supplied from the left internal carotid
      artery via the anterior communicating artery. The investigations conducted show
      that the computational fluid dynamic tool, which provides high resolution in both
      time and space domains, can be used to support physicians in diagnosing patients
      of different ages and various anatomical arterial structures. 

PMID- 24674599
TI  - Identification of dipeptidyl peptidase IV inhibitors: virtual screening,
      synthesis and biological evaluation.
AB  - Inhibition of dipeptidyl peptidase IV is an important approach for the treatment
      of type-2 diabetes. In this study, we reported a multistage virtual screening
      workflow that integrated 3D pharmacophore models, structural consensus docking,
      and molecular mechanics/generalized Born surface area binding energy calculation
      to identify novel dipeptidyl peptidase IV inhibitors. After screening our in
      house database, two hit compounds, HWL-405 and HWL-892, having persistent high
      performance in all stages of virtual screening were identified. These two hit
      compounds together with several analogs were synthesized and evaluated for in
      vitro inhibition of dipeptidyl peptidase IV. The experimental data indicated that
      most designed compounds exhibited significant dipeptidyl peptidase IV inhibitory
      activity. Among them, compounds 35f displayed the greatest potency against
      dipeptidyl peptidase IV in vitro with the IC50 value of 78 nm. In an oral glucose
      tolerance test in normal male Kunming mice, compound 35f reduced blood glucose
      excursion in a dose-dependent manner. 

PMID- 24674600
TI  - Calcium imaging of infrared-stimulated activity in rodent brain.
AB  - Infrared neural stimulation (INS) is a promising neurostimulation technique that
      can activate neural tissue with high spatial precision and without the need for
      exogenous agents. However, little is understood about how infrared light
      interacts with neural tissue on a cellular level, particularly within the living
      brain. In this study, we use calcium sensitive dye imaging on macroscopic and
      microscopic scales to explore the spatiotemporal effects of INS on cortical
      calcium dynamics. The INS-evoked calcium signal that was observed exhibited a
      fast and slow component suggesting activation of multiple cellular mechanisms.
      The slow component of the evoked signal exhibited wave-like properties suggesting
      network activation, and was verified to originate from astrocytes through
      pharmacology and 2-photon imaging. We also provide evidence that the fast calcium
      signal may have been evoked through modulation of glutamate transients. This
      study demonstrates that pulsed infrared light can induce intracellular calcium
      modulations in both astrocytes and neurons, providing new insights into the
      mechanisms of action of INS in the brain. 

PMID- 24674602
TI  - Prevalence and formation of primary cataracts and persistent hyperplastic tunica
      vasculosa lentis in the German Pinscher population in Germany.
AB  - OBJECTIVE: The objective of this study was to describe the prevalences of primary
      noncongenital cataracts (CAT) and persistent hyperplastic tunica vasculosa lentis
      (PHTVL) in the German Pinscher population in Germany and to analyze the mode of
      inheritance of CAT in this dog breed. ANIMALS STUDIED: All German Pinschers with
      a certified veterinary ophthalmological diagnosis and born between 1993 and 2010
      were included in this study. Examinations were performed between 1997 and 2013 by
      certified veterinary ophthalmologists of the German panel of the European Eye
      Scheme for Diagnosis of Inherited Eye Diseases in Animals (DOK). PROCEDURES: Data
      were reviewed retrospectively for the prevalence of PHTVL, and the prevalence,
      location and age at diagnosis of CAT. Inheritance of CAT was analyzed using the
      Singles Method. RESULTS: A total of 779 eye examination reports of 409 dogs were
      available. Primary noncongenital cataracts were diagnosed in 64 (15.6%), and
      PHTVL in 13 (3.2%) of the examined dogs. The pedigrees included 168
      ophthalmologically examined dogs with 104 CAT-unaffected and 64 CAT-affected
      dogs. All affected animals were offspring of a frequently used stud-dog or
      closely related ancestors of this stud-dog. Simple segregation analysis revealed
      a recessive mode of inheritance for CAT. CONCLUSIONS: An early onset form of CAT
      with various cortical, posterior polar or multiple locations was the most
      prevalent manifestation among close relatives in German Pinschers. The pedigree
      analysis indicated a hereditary component of cataract formation with a monogenic
      autosomal recessive pattern of inheritance.

PMID- 24674603
TI  - Phenotypic variation and selective mortality as major drivers of recruitment
      variability in fishes.
AB  - An individual's phenotype will usually influence its probability of survival.
      However, when evaluating the dynamics of populations, the role of selective
      mortality is not always clear. Not all mortality is selective, patterns of
      selective mortality may vary, and it is often unknown how selective mortality
      compares or interacts with other sources of mortality. As a result, there is
      seldom a clear expectation for how changes in the phenotypic composition of
      populations will translate into differences in average survival. We address these
      issues by evaluating how selective mortality affects recruitment of fish
      populations. First, we provide a quantitative review of selective mortality. Our
      results show that most of the mortality during early life is selective, and that
      variation in phenotypes can have large effects on survival. Next, we describe an
      analytical framework that accounts for variation in selection, while also
      describing the amount of selective mortality experienced by different cohorts
      recruiting to a single population. This framework is based on reconstructing
      fitness surfaces from phenotypic selection measurements, and can be employed for
      either single or multiple traits. Finally, we show how this framework can be
      integrated with models of density-dependent survival to improve our understanding
      of recruitment variability and population dynamics. 

PMID- 24674601
TI  - Effects of endogenous cannabinoid anandamide on cardiac Na+/Ca2+ exchanger.
AB  - Endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) has been shown to
      cause negative inotropic and antiarrhythmic effects in ventricular myocytes. In
      this study, using whole-cell patch clamp technique, we have investigated the
      effects of AEA on cardiac Na(+)/Ca(2+) exchanger (NCX1)-mediated currents. AEA
      suppressed NCX1 with an IC50 value of 4.7 MUM. Both inward and outward components
      of exchanger currents were suppressed by AEA equally. AEA inhibition was mimicked
      by the metabolically stable analogue, methanandamide (metAEA, 10 MUM) while it
      was not influenced by inhibition of fatty acid amide hydrolase with 1 MUM URB597
      incubation. The effect of AEA, was not altered in the presence of cannabinoid
      receptor 1 and 2 antagonists AM251 (1 MUM) and AM630 (1 MUM), respectively. In
      addition, inhibition by AEA remained unchanged after pertussis toxin (PTX, 2
      MUg/ml) treatment or following the inclusion of GDP-beta-S (1 mM) in pipette
      solution. Currents mediated by NCX1 expressed in HEK-293 cells were also
      inhibited by 10 MUM AEA a partially reversible manner. Confocal microscopy images
      indicated that the intensity of YFP-NCX1 expression on cell surface was not
      altered by AEA. Collectively, the results indicate that AEA directly inhibits the
      function of NCX1 in rat ventricular myocytes and in HEK-293 cells expressing
      NCX1.

PMID- 24674604
TI  - Radiographic characterization of primary lung tumors in 74 dogs.
AB  - Primary pulmonary neoplasia is well recognized in dogs and prognosis depends upon
      the tumor type. The purpose of this retrospective study was to characterize the
      radiographic appearance of different primary lung tumors with the goal of
      establishing imaging criteria to separate the different types. Three-view
      thoracic radiographs of 74 dogs with histologically confirmed pulmonary
      anaplastic carcinoma (n = 2), adenocarcinoma (n = 31), bronchioalveolar carcinoma
      (n = 19), histiocytic sarcoma (n = 21), and squamous cell carcinoma (n = 1) were
      evaluated. Radiographs were assessed for tumor volume, affected lobe, location
      within lobe, overall pulmonary pattern, presence of cavitation, mineralization,
      air bronchograms, lymphadenomegaly, and pleural fluid. Histiocytic sarcomas were
      significantly larger than other tumor types (271 cm(3); P = 0.009) and most
      likely to be found in the left cranial (38%; 8/21) and right middle (43%; 9/21)
      lung lobes, whereas adenocarcinomas were most likely to be found in the left
      caudal (29%; 9/31) lung lobe. Fifty-seven percent (12/21) of histiocytic sarcomas
      had an internal air bronchogram. Findings indicate that a large mass in the
      periphery or affecting the whole lobe of the right middle or left cranial lung
      lobe with an internal air bronchogram is likely to be an histiocytic sarcoma.

PMID- 24674605
TI  - High prevalence of pfcrt-CVIET haplotype in isolates from asymptomatic and
      symptomatic patients in south-central Oromia, Ethiopia.
AB  - BACKGROUND: As a result of extensive chloroquine resistance (CQR) in Plasmodium
      falciparum in late 1990s, Ethiopia replaced CQ with sulphadoxine-pyrimethamine
      (SP) as first-line drug, which in turn was replaced by artemisinin combination
      therapy in 2004. Plasmodium falciparum resistance to CQ is determined by the
      mutation at K76T of the P. falciparum chloroquine resistance transporter (pfcrt)
      gene. Understanding diversity in the P. falciparum genome is crucial since it has
      the potential to influence important phenotypes of the parasite such as drug
      resistance. Limited data is available regarding the type of pfcrt mutant allelic
      type, the effect of CQ withdrawal and diversity of the parasite population in
      south-central Oromia, Ethiopia. METHODS: Finger-pricked blood spotted on Whatman
      3MM filter papers were collected from falciparum malaria patients. Parasite DNA
      was extracted from individual blood spots on the filter papers. The presence of
      K76T mutations was determined using nested PCR for all isolates. Complete
      sequencing of mutations in pfcrt 72-76 was done for a set of randomly selected
      resistant isolates. Four microsatellite (MS) markers were analysed to determine
      the heterozygosity. RESULTS: Although CQ was withdrawn for more than a decade,
      100% of the parasites still carried the pfcrt K76T mutation. All isolates were
      mutant at the K76T polymorphism. Based on combinations of MS markers, seven
      different Ethiopian CQR variants (E1-E7) were identified. Heterozygosity (H(e))
      for MS flanking the pfcrt chloroquine resistance allele ranged from 0.00 (mscrt 
      29, -29.268 kb) to 0.21 (mscrt -2, -2.814 kb). H(e) ranged from 0.00 (msint 3, 0
      kb) to 0.19 (msint 2, 0 kb) for MS within the pfcrt gene. Both intronic and MS
      flanking the pfcrt gene showed low levels of diversity. CONCLUSION: pfcrt CQR
      allele seems to be fixed in the study area. Of the different haplotypes
      associated with CQR, only the CVIET genotype was identified. No reversal to the
      wild-type has occurred in Ethiopia unlike in many Africa countries where CQR
      parasites declined after cessation of CQ use. Decreased diversity in CQR isolates
      surrounding pfcrt suggests CQ selection and homogenization among CQR parasite
      population. While mutation in msint 3 and mscrt -29 of the mutant pfcrt allele is
      being fixed, it seems that mutations in msint 2 and mscrt -2 are still evolving
      and may indicate the start of re-diversification of the population from a fixed
      76 T population.

PMID- 24674606
TI  - Psoriatic arthritis: an update.
AB  - Advances in our understanding of the pathogenesis of psoriatic arthritis and
      clinical aspects of the disease justify the present review. Studies have
      identified common inflammatory pathways related to the innate immune response,
      such as the IL-12/IL-23 axis, along with numerous genes that affect
      susceptibility to both diseases and influence phenotypic development. Interest
      has grown in biomarkers that can be used for early diagnosis or prognosis or to
      predict joint destruction and the response to treatment. Recent reports describe
      important differences between the effects of disease-modifying antirheumatic
      drugs and biologics on the process of new bone formation. Other issues that have
      been discussed include the need for reliable screening methods, particularly for
      early detection of oligoarticular arthritis, and for protocols to guide referral
      to specialists, especially in newly created multidisciplinary practices. 

PMID- 24674607
TI  - The role of filaggrin in the skin barrier and disease development.
AB  - Filaggrin is a structural protein that is fundamental in the development and
      maintenance of the skin barrier. The function of filaggrin and its involvement in
      various cutaneous and extracutaneous disorders has been the subject of
      considerable research in recent years. Mutations in FLG, the gene that encodes
      filaggrin, have been shown to cause ichthyosis vulgaris, increase the risk of
      atopic dermatitis and other atopic diseases, and exacerbate certain conditions.
      The present article reviews the current knowledge on the role of filaggrin in the
      skin barrier, FLG mutations, and the consequences of filaggrin deficiency. 

PMID- 24674608
TI  - Arthroscopic reduction of comminuted intra-articular distal radius fractures with
      diaphyseal-metaphyseal comminution.
AB  - PURPOSE: In the setting of severely comminuted diaphyseal-metaphyseal fractures
      of the distal radius, arthroscopic reduction of the joint surface is difficult
      and often results in shortening and collapse. Yet, several authors have shown the
      benefits of arthroscopy in articular distal radius fractures. We present a method
      that safely allows a combination of arthroscopic reduction and rigid fixation and
      describe the outcomes in a small group of patients. METHODS: Four consecutive
      patients with severely comminuted diaphyseal-metaphyseal articular fractures of
      the distal radius were treated using the stable reference fragment technique. For
      all cases, we used an extra-long volar locking plate applied to the diaphysis of
      the radius. Preoperative computed tomography scanning was used to identify the
      largest articular fragment. This reference fragment was reduced and stabilized
      with locking pegs or screws to the volar plate under fluoroscopic guidance. The
      articular reduction continued arthroscopically, using the reference fragment as a
      guide. Once the articular reduction was complete, the comminuted metaphysis was
      addressed and secured to the plate. RESULTS: All patients achieved excellent
      clinical and radiological results. Flexion-extension averaged 124 degrees  and
      pronation-supination averaged 174 degrees . One patient showed minor signs of
      radiocarpal osteoarthritis on radiographs at 3 years. CONCLUSIONS: By securing
      the reference fragment before addressing the metaphyseal comminution, a stable
      platform was created. Thus, intra-articular reduction was achieved while
      maintaining extra-articular alignment. Although the results were excellent, the
      number of cases was small. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24674609
TI  - Factors influencing infection rates after open fractures of the radius and/or
      ulna.
AB  - PURPOSE: To investigate factors associated with the development of deep infection
      in patients with open fractures of the radius and/or ulna. METHODS: We
      retrospectively reviewed 296 open fractures of the radius and/or ulna. Of these
      patients, 200 had at least 6-month follow-up and were included in this study. The
      following variables were examined for each patient: time from injury to
      antibiotic administration, time from injury to operative debridement, Gustilo
      Anderson classification, type of antibiotic received, and host characteristics
      such as age, diabetes, and tobacco use. Outcome parameters included the presence
      of deep infection and fracture union. RESULTS: The overall rate of deep infection
      was 5% (10 of 200). No type 1 fractures (of 41) developed deep infection. In
      contrast, 4% (2 of 48) of type 2 and 7% (8 of 110) of type 3 fractures developed
      infection. Of 200 patients, 28 received antibiotics in less than 3 hours and
      underwent debridement in less than 6 hours from the time of injury; however, they
      did not have lower rates of infection. Similar findings were noted when nonunion
      was used as the outcome, and the association between Gustilo-Anderson
      classification and the development of nonunion was statistically significant.
      CONCLUSIONS: Factors such as time to antibiotics and time to operative
      debridement were not predictors for either rate of deep infection or nonunion in
      open fractures of the radius and/or ulna. The type of fracture as outlined by the
      Gustilo-Anderson classification was the factor most strongly associated with the
      development of deep infection and nonunion in these fractures. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 24674610
TI  - Early results of anterior elbow release with and without biceps lengthening in
      patients with cerebral palsy.
AB  - PURPOSE: To investigate the effect of partial biceps lengthening on elbow flexion
      posture and active elbow flexion and extension in patients with cerebral palsy.
      METHODS: We retrospectively reviewed 29 patients with cerebral palsy who
      underwent anterior elbow release as part of multilevel upper extremity surgery.
      The early series of the patients (N = 14; group 1) had lacertus fibrosus
      division, brachialis fractional lengthening, and denuding of the pretendinous
      adventitia off the biceps tendon. The later series of patients (N = 15; group 2)
      had partial biceps tendon lengthening in addition to the procedures in group 1.
      We compared the 2 sets of patients for elbow flexion posture, active elbow
      flexion and extension, forearm rotation, and House scores, with mean follow-ups
      of 72 months for group 1 and 31 months for group 2. RESULTS: The 2 groups were
      comparable in terms of mean age, number of procedures, and preoperative House
      scores. Group 2 patients had more improvement in flexion posture (53 degrees  vs.
      44 degrees ) and active extension (23 degrees  vs. 15 degrees ) than group 1
      postoperatively. However, group 2 had a mean decrease of 7 degrees  in active
      elbow flexion, whereas group 1 had no changes. There was no difference in forearm
      supination or in the improvement of House scores between groups. CONCLUSIONS:
      Early results of partial lengthening of the biceps tendon showed that it may
      improve elbow flexion posture and active elbow extension in patients with flexion
      deformity in cerebral palsy. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 24674612
TI  - Relationship of bone mineral density of spine and femoral neck to distal radius
      fracture stability in patients over 65.
AB  - PURPOSE: We hypothesized that an increasing degree of osteopenia in the femoral
      neck and lumbar spine would be associated with loss of reduction after closed
      manipulation and splinting of distal radius fractures in patients over 65 years
      of age. METHODS: We performed a retrospective review, evaluating 78 patients with
      displaced distal radius fractures managed with closed reduction and splinting. T
      scores from the lumbar spine and femoral neck were recorded from dual-energy x
      ray absorptiometry scans performed either within 1 year before or after injury.
      Volar tilt, radial height, radial inclination, and ulnar variance were evaluated
      from the initial fracture, postreduction, and final follow-up radiographs. We
      calculated the percentage of reduction maintained regarding reduction variable.
      We correlated T-scores of the lumbar spine and femoral neck with the percentage
      of retained reduction. RESULTS: We found no correlation between T-scores of the
      lumbar spine or femoral neck and the amount of reduction lost throughout the
      healing process of distal radius fractures with respect to volar tilt, radial
      height, radial inclination, or ulnar variance. Reduction was of no anatomical
      benefit in 53% to radial height, 44% to radial inclination, and 54% to ulnar
      variance. CONCLUSIONS: There appears to be no relationship between bone mineral
      density, based on T-scores of the lumbar spine and femoral neck, and the ability
      to maintain reduction after closed manipulation and splinting of displaced distal
      radius fractures in patients over 65 years of age. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic III.

PMID- 24674611
TI  - The influence of surgeon age on distal radius fracture treatment in the United
      States: a population-based study.
AB  - PURPOSE: This study attempted to determine the extent to which surgeon age
      influences treatment patterns for distal radius fractures (DRFs). We hypothesized
      that younger surgeons perform open reduction internal fixation (ORIF) for DRFs
      among elderly individuals more frequently than older surgeons, who employ a wider
      range of treatment modalities. METHODS: We identified 61,314 Medicare
      beneficiaries who experienced DRFs and the 12,823 surgeons who performed ORIF,
      external fixation, pinning, or closed reduction on them during 2007. We examined
      the effect of surgeon age on DRF treatment pattern, controlling for patient
      characteristics and other surgeon factors using multinomial logistic regression.
      We then stratified our analysis by American Society for Surgery of the Hand
      membership to more closely examine the influence of surgeon specialization on the
      association between surgeon age and DRF treatment. RESULTS: Surgeons aged 40
      years and younger were more likely to perform ORIF and less likely to choose
      external fixation and percutaneous pinning to treat DRFs, compared with older
      surgeons. Surgeon specialization mitigated this relationship, and American
      Society for Surgery of the Hand members were more likely to choose ORIF compared
      with nonmembers. However, surgeon age remained a significant predictor of
      treatment choice after controlling for other factors and surgeon specialization.
      CONCLUSIONS: Younger surgeons are more likely to perform ORIF for DRFs among
      Medicare beneficiaries over 65 years of age. Given the lack of evidence
      supporting any single treatment option for DRF, understanding the factors that
      drive dissemination of operative techniques may provide insight into treatment
      disparities within the Medicare population. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic III.

PMID- 24674613
TI  - Attrition or rupture of digital extensor tendons due to carpal boss: report of 2
      cases.
AB  - We present 2 cases that demonstrate the potential for tendon involvement in the
      presence of a carpal boss. In the first, a patient presented with tendon rupture
      without antecedent pain. In the second, pain and tendon irritation prompted
      magnetic resonance imaging that revealed tendon fraying, which was confirmed at
      surgery. These cases illustrate the potential for tendinous sequelae of a carpal
      boss. Advanced imaging may be considered when tendon irritation is clinically
      suspected. Attention to the possibility of tendon rupture in the setting of an
      otherwise asymptomatic carpal boss is advised. 

PMID- 24674614
TI  - Dorsal surgical approaches to the proximal interphalangeal joint: a comparative
      anatomic study.
AB  - PURPOSE: Adequate exposure of the articular surface of the head of the proximal
      phalanx is essential for reduction of intra-articular fractures of the proximal
      interphalangeal (PIP) joint. We compared the articular exposure obtained by a
      dorsal extensor-tendon splitting (Swanson), an extensor tendon-reflecting
      (Chamay), and an extensor mechanism-sparing approach. METHODS: The PIP joints of
      24 digits from 6 fresh-frozen cadaveric specimens were randomly assigned to 1 of
      3 dorsal surgical exposures: an extensor tendon-splitting, extensor tendon
      reflecting, or extensor mechanism-sparing approach. The exposed surface was
      painted with methylene blue and the PIP joints were disarticulated to reveal the
      distal articular surface of the proximal phalanx. Using 3-dimensional digital
      mapping, we calculated the percentage of the exposed dyed surface area to the
      total surface area and compared the 3 approaches. RESULTS: The mean percent
      exposed joint surface area for the extensor tendon-splitting, extensor tendon
      reflecting, and extensor mechanism-sparing approaches were 41%, 52%, and 16%,
      respectively. Each approach provided a significantly different percentage of
      articular PIP joint surface area from the other 2. CONCLUSIONS: The amount of
      articular surface visualized using 3 dorsal approaches to the PIP joint must be
      weighed against the amount of extensor mechanism violated. Exposure of the
      articular surface by the extensor mechanism-sparing approach to the PIP joint
      allowed nearly a third of the exposure gained by the extensor tendon-reflecting
      exposure. Although the extensor tendon-reflecting technique revealed the greatest
      amount of surface, nearly 50% of the proximal phalanx articular surface remained
      inaccessible as long as the collateral ligaments were intact. CLINICAL RELEVANCE:
      Understanding the limitations inherent in dorsal exposure of the PIP joint may
      help guide the surgical approach for the individual patient.

PMID- 24674615
TI  - Direct repair for managing acute and chronic lateral ulnar collateral ligament
      disruptions.
AB  - PURPOSE: Acute elbow injuries that disrupt the lateral ulnar collateral ligament
      and result in posterolateral rotatory instability usually require surgical
      treatment. The 2 technical options reported, direct repair and use of a palmaris
      longus tendon graft, have usually favored the use of the graft. To balance this
      emphasis, we report our experience with direct repair of the humeral origin in
      cases of trauma, whether acute, delayed, or recurrent. It was our hypothesis that
      because the humeral origin is the point of failure and separation, restoration of
      this attachment is sufficient to restore stability and durable function without
      the need for a graft. METHODS: Patients with complete disruption of the
      posterolateral ligaments of the elbow, who were managed with direct repair to the
      humeral origin, were included. Patients were separated into an acute treatment
      group (< 30 d from injury to treatment) and a delayed treatment group (> 30 d).
      Mayo Elbow Performance Scores and postoperative range of motion were collected
      from patient records. RESULTS: A total of 34 patients were included with a mean
      follow-up of 42 months. No difference was seen in Mayo Elbow Performance Scores
      between acute (mean, 90) or delayed treatment (mean, 89) of the lateral ulnar
      collateral ligament tear. No difference was seen in final elbow flexion or
      extension. Two patients in the acute group had failure of the direct repair
      requiring intervention. In the delayed group, no patients had recurrent
      instability. CONCLUSIONS: No significant difference in clinical outcome or range
      of motion was observed after direct repair of traumatic tears of the lateral
      ulnar collateral ligament tear between acute and delayed treatment cohorts.
      Despite complete disruption of the posterolateral ligaments, direct repair of the
      torn ligament to its humeral origin was effective without supplemental tendon
      graft reconstruction irrespective of interval from injury to repair, mechanism of
      injury, or associated fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      III.

PMID- 24674616
TI  - An investigation into the relationship between region specific quality of life
      and adverse tuberculosis treatment outcomes in Istanbul, Turkey.
AB  - BACKGROUND AND OBJECTIVE: Istanbul has the highest incidence of tuberculosis (TB)
      in Turkey. It is also the largest city, with considerable differences in quality
      of life across its urban regions. The aim of this study is to investigate the
      relationship between (i) the diverse quality of life across specific urban
      regions, (ii) TB incidence rates, inclusive of demographic and clinical
      characteristics of TB patients, and (iii) adverse treatment outcomes. METHODS:
      This retrospective study included 23,845 new TB patients (recorded in the
      National TB Registry between 2006 and 2010) in Istanbul. Thirty-nine urban
      districts of Istanbul were ranked into five groups on the basis of an urban
      quality of life index. Patient data were matched with these groups, and further
      categorized according to 'age', 'sex', 'country of birth' and 'antibiotics
      resistance'. Adverse treatment outcomes and TB incidence rates were extracted
      from official records. Logistic regression, clustered analyses, 95% CI and p
      values (STATA) were reported to describe the association between variables.
      RESULTS: Six per cent of total cases had 'at least one adverse treatment outcome'
      (default 3.8%, failure 0.5%, death 1.7% in total cases). 'An adverse treatment
      outcome' was found to be associated with age OR (CI 95%) (1.02 (1.01-1.03));
      'male sex' 1.65 (1.28-2.12); 'other country of birth' 4.82 (3.05-7.62); 100,000
      per 'over 60' insidence goups 1.61 (1.32-1.97), the lowest quality of life index
      0.65 (0.47-0.83). CONCLUSIONS: Patients with high tuberculosis risk factors
      living in high incidence regions need to be closely monitored. Patients living in
      lower ranking regions are more likely to have 'poor treatment outcomes'.

PMID- 24674617
TI  - Prevention of ventilator-associated pneumonia.
AB  - Invasive mechanical ventilation (IMV) represents a risk factor for the
      development of ventilator-associated pneumonia (VAP), which develops at least 48h
      after admission in patients ventilated through tracheostomy or endotracheal
      intubation. VAP is the most frequent intensive-care-unit (ICU)-acquired infection
      among patients receiving IMV. It contributes to an increase in hospital
      mortality, duration of MV and ICU and length of hospital stay. Therefore, it
      worsens the condition of the critical patient and increases the total cost of
      hospitalization. The introduction of preventive measures has become imperative,
      to ensure control and to reduce the incidence of VAP. Preventive measures focus
      on modifiable risk factors, mediated by non-pharmacological and pharmacological
      evidence based strategies recommended by guidelines. These measures are intended
      to reduce the risk associated with endotracheal intubation and to prevent
      microaspiration of pathogens to the lower airways. 

PMID- 24674618
TI  - Expression of tissue factor in canine mammary tumours and correlation with grade,
      stage and markers of haemostasis and inflammation.
AB  - Tissue factor (TF) expression in human cancers has been associated with a
      procoagulant state and facilitation of metastasis. This study was conducted in
      order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial
      mammary tumours from 28 dogs were included. TF expression of the tumours was
      evaluated by immunohistochemistry using a polyclonal antibody against recombinant
      canine TF. In addition, thromboelastography, haemostatic and inflammatory
      parameters were evaluated in the patients. TF was recognized in 44% of benign and
      58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic
      luminal epithelial cells and/or diffusely in the cytoplasm. No association was
      found between TF expression and stage or grade of disease. A significant
      association between TF expression and antithrombin and plasminogen was found, and
      extensive TF expression was seen in a lymph node metastasis classified as
      anaplastic mammary carcinoma from a dog with concomitant disseminated
      intravascular coagulation (DIC). 

PMID- 24674619
TI  - Pseudoexfoliation and mortality: a population-based 30-year follow-up study.
AB  - PURPOSE: To study the relationship between pseudoexfoliation (PEX) and all-cause
      mortality in a population in which PEX is a common finding. METHODS: Survival
      analyses were performed in a cohort of 760 residents 65-74 years of age, examined
      in a population survey in the municipality of Tierp, Sweden, 1984-86. To expand
      the cohort, participants in other studies in Tierp were enrolled. Additionally,
      people were recruited by means of glaucoma case records established at the Eye
      Department in Tierp in 1978-2007. In this way, the cohort comprised 1524
      subjects, representing more than 21,100 person-years at risk. Information on
      deaths was obtained from the local population register. RESULTS: By the
      conclusion of the study, in August 2013, 1280 deaths had been reported. Of these
      cases, 350 were affected by PEX at baseline. No association between PEX and
      mortality was found (hazard ratio 1.00; 95% confidence interval 0.88-1.14).
      CONCLUSION: The results strongly suggest that PEX had no effect on all-cause
      mortality in the population under study.

PMID- 24674620
TI  - Open questions: microbes, metabolism and host-pathogen interactions.

PMID- 24674621
TI  - Unusual masturbatory practice as an etiological factor in the diagnosis and
      treatment of sexual dysfunction in young men.
AB  - INTRODUCTION: Masturbation is a common sexual activity among people of all ages
      throughout life. It has been traditionally prohibited and judged as immoral and
      sinful by several religions. Although it is no longer perceived as a negative
      behavior, masturbation is often omitted in the diagnostic inquiry of patients
      with sexual problems. AIMS: The aims of this study are to increase the awareness
      of clinicians to the importance of including questions regarding masturbatory
      habits in the process of sexual history taking, to analyze cases of male sexual
      dysfunction (SD) associated with unusual masturbatory practices, and to propose a
      practical tool for clinicians to diagnose and manage such problems. METHODS: A
      clinical study of four cases that include a range of unusual masturbatory
      practices by young males who applied for sex therapy is described. An
      intervention plan involving specific questions in case history taking was
      devised. It was based on detailed understanding of each patient's masturbatory
      practice and its manifestation in his SD. MAIN OUTCOME MEASURES: Effects of
      identifying and altering masturbatory practices on sexual function. RESULTS: The
      four men described unusual and awkward masturbatory practices, each of which was
      associated with different kinds of SD. The unlearning of the masturbatory
      practices contributed notably to improvement of their sexual function.
      CONCLUSIONS: The four cases in this study indicate that the detailed questioning
      of masturbatory habits is crucial for a thorough assessment and adequate
      treatment of sexual problems in men. We propose specific questions on
      masturbatory behavior as well as a diagnostic and therapeutic flowchart for
      physicians and sex therapists to address those problems.

PMID- 24674622
TI  - Exploring relationships between whole carcass condemnation abattoir data, non
      disease factors and disease outbreaks in swine herds in Ontario (2001-2007).
AB  - BACKGROUND: Improving upon traditional animal disease surveillance systems may
      allow more rapid detection of disease outbreaks in animal populations. In
      Ontario, between the years 2001 - 2007, widespread outbreaks of several diseases
      caused major impacts to the swine industry. This study was undertaken to
      investigate whether whole carcass condemnation data of market pigs from
      provincial abattoirs from 2001 - 2007 could have provided useful information for
      disease surveillance of Ontario swine. The objective was to examine the
      suitability of these data for detection of disease outbreaks using multi-level
      models and spatial scan statistics. We investigated the ability of these data to
      provide spatially-relevant surveillance information by determining the
      approximate distance pigs are shipped from farm to provincial abattoirs in the
      province, and explored potentially biasing non-disease factors within these data.
      RESULTS: Provincially-inspected abattoirs in Ontario were found to be located in
      close proximity to the hog farms of origin. The fall season and increasing
      abattoir capacity were associated with a decrease in condemnation rates.
      Condemnation rates varied across agricultural regions by year, and some regions
      showed yearly trends consistent with the timing of emergence of new disease
      strains that affected the Ontario swine population. Scan statistics identified
      stable clusters of condemnations in space that may have represented stable
      underlying factors influencing condemnations. The temporal scans detected the
      most likely cluster of high condemnations during the timeframe in which
      widespread disease events were documented. One space-time cluster took place
      during the beginning of the historical disease outbreaks and may have provided an
      early warning signal within a syndromic surveillance system. CONCLUSIONS: Spatial
      disease surveillance methods may be applicable to whole carcass condemnation data
      collected at provincially-inspected abattoirs in Ontario for disease detection on
      a local scale. These data could provide useful information within a syndromic
      disease surveillance system for protecting swine herd health within the province.
      However, non-disease factors including region, season and abattoir size need to
      be considered when applying quantitative methods to abattoir data for disease
      surveillance.

PMID- 24674623
TI  - The PCNA binding domain of Rad2p plays a role in mutagenesis by modulating the
      cell cycle in response to DNA damage.
AB  - The xeroderma pigmentosum group G (XPG) gene, encoding an essential element in
      nucleotide excision repair (NER), has a proliferating cell nuclear antigen
      binding domain (PCNA-BD) at its C-terminal region. However, the role of this
      domain is controversial because its presence does not affect NER. Using yeast
      RAD2, a homolog of human XPG, we show that Rad2p interacts with PCNA through its
      PCNA-BD and the PCNA-BD of Rad2p plays a role in UV-induced mutagenesis. While a
      mutation of Rad2p endonuclease activity alone causes dramatically increased
      mutation rates and UV sensitivity, as well as growth retardation after UV
      irradiation, a mutation of the Rad2p PCNA-BD in the same mutant causes
      dramatically decreased mutation rates, reduced UV sensitivity and increased
      growth rate after UV irradiation. After UV irradiation, large-budded cells of
      Rad2p endonuclease defective mutants wane due to a mutation of the Rad2p PCNA-BD.
      Besides, the Rad2p PCNA-BD mutant protein exhibits alleviated PCNA-binding
      efficiency. These results show a hitherto unsuspected role of the Rad2p PCNA-BD
      that controls mutagenesis via cell cycle modulation together with PCNA.
      Furthermore, the high mutation rate of cells with other NER gene mutations was
      also decreased by the mutation of the Rad2p PCNA-BD, which indicates that the
      Rad2p-PCNA interaction might be responsible for mutagenesis control in the
      general NER pathway. Our results suggest that the drastically increased incidence
      of skin cancer in xeroderma pigmentosum patients could arise from the synergistic
      effects between cell cycle arrest due to the XPG-PCNA interaction and the
      accumulation of damaged DNA via defects in DNA damage repair. 

PMID- 24674625
TI  - The mechanism of negative DNA supercoiling: a cascade of DNA-induced
      conformational changes prepares gyrase for strand passage.
AB  - DNA topoisomerases inter-convert different DNA topoisomers in the cell. They
      catalyze the introduction or relaxation of DNA supercoils, as well as catenation
      and decatenation. Members of the type I topoisomerase family cleave a single
      strand of their double-stranded DNA substrate, whereas enzymes of the type II
      family cleave both DNA strands. Bacterial DNA gyrase, a type II topoisomerase,
      catalyzes the introduction of negative supercoils into DNA in an ATP-dependent
      reaction. Gyrase is not present in humans, and constitutes an attractive drug
      target for the treatment of bacterial and parasite infections. DNA supercoiling
      by gyrase is believed to occur by a strand passage mechanism, in which one
      segment of the double-stranded DNA substrate is passed through a (transient)
      break in a second segment. This mechanism requires the coordinated opening and
      closing of three protein interfaces, so-called gates, to ensure the
      directionality of strand passage toward negative supercoiling. Single molecule
      fluorescence resonance energy transfer experiments are ideally suited to
      investigate conformational changes during the catalytic cycle of DNA
      topoisomerases. In this review, we summarize the current knowledge on the cascade
      of DNA- and nucleotide-induced conformational changes in gyrase that lead to
      strand passage and negative supercoiling of DNA. We discuss how these
      conformational changes couple ATP hydrolysis to DNA supercoiling in gyrase, and
      how the common mechanistic principle of coordinated gate opening and closing is
      modulated to allow for the catalysis of different reactions by different type II
      topoisomerases. 

PMID- 24674624
TI  - Functional overlaps between XLF and the ATM-dependent DNA double strand break
      response.
AB  - Developing B and T lymphocytes generate programmed DNA double strand breaks
      (DSBs) during the V(D)J recombination process that assembles exons that encode
      the antigen-binding variable regions of antibodies. In addition, mature B
      lymphocytes generate programmed DSBs during the immunoglobulin heavy chain (IgH)
      class switch recombination (CSR) process that allows expression of different
      antibody heavy chain constant regions that provide different effector functions.
      During both V(D)J recombination and CSR, DSB intermediates are sensed by the ATM
      dependent DSB response (DSBR) pathway, which also contributes to their joining
      via classical non-homologous end-joining (C-NHEJ). The precise nature of the
      interplay between the DSBR and C-NHEJ pathways in the context of DSB repair via C
      NHEJ remains under investigation. Recent studies have shown that the XLF C-NHEJ
      factor has functional redundancy with several members of the ATM-dependent DSBR
      pathway in C-NHEJ, highlighting unappreciated major roles for both XLF as well as
      the DSBR in V(D)J recombination, CSR and C-NHEJ in general. In this review, we
      discuss current knowledge of the mechanisms that contribute to the repair of DSBs
      generated during B lymphocyte development and activation with a focus on
      potential functionally redundant roles of XLF and ATM-dependent DSBR factors. 

PMID- 24674626
TI  - Chromatin remodelling complex RSC promotes base excision repair in chromatin of
      Saccharomyces cerevisiae.
AB  - The base excision repair (BER) pathway is a conserved DNA repair system required
      to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells.
      Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is
      poorly understood. We have investigated the role of an essential ATP-dependent
      chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in
      BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of
      RSC, causes enhanced sensitivity to the DNA alkylating agent methyl
      methanesulfonate (MMS) and results in a substantial inhibition of BER, at the
      GAL1 locus and in the genome overall. Consistent with this observation, the DNA
      in chromatin is less accessible to micrococcal nuclease digestion in the absence
      of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted
      cells is not due to changes in the expression of BER genes. Collectively, our
      data indicates the RSC complex promotes efficient BER in chromatin. These results
      provide, for the first time, a link between ATP-dependent chromatin remodelling
      and BER in living cells. 

PMID- 24674627
TI  - Overexpression of DNA ligase III in mitochondria protects cells against oxidative
      stress and improves mitochondrial DNA base excision repair.
AB  - Base excision repair (BER) is the most prominent DNA repair pathway in human
      mitochondria. BER also results in a temporary generation of AP-sites, single
      strand breaks and nucleotide gaps. Thus, incomplete BER can result in the
      generation of DNA repair intermediates that can disrupt mitochondrial DNA
      replication and transcription and generate mutations. We carried out BER analysis
      in highly purified mitochondrial extracts from human cell lines U2OS and HeLa,
      and mouse brain using a circular DNA substrate containing a lesion at a specific
      position. We found that DNA ligation is significantly slower than the preceding
      mitochondrial BER steps. Overexpression of DNA ligase III in mitochondria
      improved the rate of overall BER, increased cell survival after menadione induced
      oxidative stress and reduced autophagy following the inhibition of the
      mitochondrial electron transport chain complex I by rotenone. Our results suggest
      that the amount of DNA ligase III in mitochondria may be critical for cell
      survival following prolonged oxidative stress, and demonstrate a functional link
      between mitochondrial DNA damage and repair, cell survival upon oxidative stress,
      and removal of dysfunctional mitochondria by autophagy. 

PMID- 24674628
TI  - Genetic factors in individual radiation sensitivity.
AB  - Cancer risk and radiation sensitivity are often associated with alterations in
      DNA repair, cell cycle, or apoptotic pathways. Interindividual variability in
      mutagen or radiation sensitivity and in cancer susceptibility may also be traced
      back to polymorphisms of genes affecting e.g. DNA repair capacity. We studied
      possible associations between 70 polymorphisms of 12 DNA repair genes with basal
      and initial DNA damage and with repair thereof. We investigated DNA damage
      induced by ionizing radiation in lymphocytes isolated from 177 young lung cancer
      patients and 169 cancer-free controls. We also sought replication of our findings
      in an independent sample of 175 families (in total 798 individuals). DNA damage
      was assessed by the Olive tail moment (OTM) of the comet assay. DNA repair
      capacity (DRC) was determined for 10, 30 and, 60min of repair. Genes involved in
      the single-strand-repair pathway (SSR; like XRCC1 and MSH2) as well as genes
      involved in the double-strand-repair pathway (DSR; like RAD50, XRCC4, MRE11 and
      ATM) were found to be associated with DNA damage. The most significant
      association was observed for marker rs3213334 (p=0.005) of XRCC1 with basal DNA
      damage (B), in both cases and controls. A clear additive effect on the logarithm
      of OTM was identified for the marker rs1001581 of the same LD-block (p=0.039):
      BCC=-1.06 (95%-CI: -1.16 to -0.96), BCT=-1.02 (95%-CI: -1.11 to -0.93) and BTT=
      0.85 (95%-CI: -1.01 to -0.68). In both cases and controls, we observed
      significantly higher DNA basal damage (p=0.007) for carriers of the genotype AA
      of marker rs2237060 of RAD50 (involved in DSR). However, this could not be
      replicated in the sample of families (p=0.781). An alteration to DRC after 30min
      of repair with respect to cases was observed as borderline significant for marker
      rs611646 of ATM (involved in DSR; p=0.055), but was the most significant finding
      in the sample of families (p=0.009). Our data indicate that gene variation
      impacts measurably on DNA damage and repair, suggesting at least a partial
      contribution to radiation sensitivity and lung cancer susceptibility. 

PMID- 24674629
TI  - Both genetic and dietary factors underlie individual differences in DNA damage
      levels and DNA repair capacity.
AB  - The interplay between dietary habits and individual genetic make-up is assumed to
      influence risk of cancer, via modulation of DNA integrity. Our aim was to
      characterize internal and external factors that underlie inter-individual
      variability in DNA damage and repair and to identify dietary habits beneficial
      for maintaining DNA integrity. Habitual diet was estimated in 340 healthy
      individuals using a food frequency questionnaire and biomarkers of antioxidant
      status were quantified in fasting blood samples. Markers of DNA integrity were
      represented by DNA strand breaks, oxidized purines, oxidized pyrimidines and a
      sum of all three as total DNA damage. DNA repair was characterized by genetic
      variants and functional activities of base and nucleotide excision repair
      pathways. Sex, fruit-based food consumption and XPG genotype were factors
      significantly associated with the level of DNA damage. DNA damage was higher in
      women (p=0.035). Fruit consumption was negatively associated with the number of
      all measured DNA lesions, and this effect was mediated mostly by beta
      cryptoxanthin and beta-tocopherol (p<0.05). XPG 1104His homozygotes appeared more
      vulnerable to DNA damage accumulation (p=0.001). Sex and individual antioxidants
      were also associated with DNA repair capacity; both the base and nucleotide
      excision repairs were lower in women and the latter increased with higher plasma
      levels of ascorbic acid and alpha-carotene (p<0.05). We have determined genetic
      and dietary factors that modulate DNA integrity. We propose that the positive
      health effect of fruit intake is partially mediated via DNA damage suppression
      and a simultaneous increase in DNA repair capacity. 

PMID- 24674630
TI  - The Rad5 helicase activity is dispensable for error-free DNA post-replication
      repair.
AB  - DNA post-replication repair (PRR) functions to bypass replication-blocking
      lesions and is subdivided into two parallel pathways: error-prone translesion DNA
      synthesis and error-free PRR. While both pathways are dependent on the
      ubiquitination of PCNA, error-free PRR utilizes noncanonical K63-linked
      polyubiquitinated PCNA to signal lesion bypass through template switch, a process
      thought to be dependent on Mms2-Ubc13 and a RING finger motif of the Rad5
      ubiquitin ligase. Previous in vitro studies demonstrated the ability of Rad5 to
      promote replication fork regression, a function dependent on its helicase
      activity. To investigate the genetic and mechanistic relationship between fork
      regression in vitro and template switch in vivo, we created and characterized
      site-specific mutations defective in the Rad5 RING or helicase activity. Our
      results indicate that both the Rad5 ubiquitin ligase and the helicase activities
      are exclusively involved in the same error-free PRR pathway. Surprisingly, the
      Rad5 helicase mutation abolishes its physical interaction with Ubc13 and the K63
      linked PCNA polyubiquitin chain assembly. Indeed, physical fusions of Rad5 with
      Ubc13 bypass the requirement for either the helicase or the RING finger domain.
      Since the helicase domain overlaps with the SWI/SNF chromatin-remodelling domain,
      our findings suggest a structural role of this domain and that the Rad5 helicase
      activity is dispensable for error-free lesion bypass. 

PMID- 24674631
TI  - In memory of John Bruce Hays (1937-2014).

PMID- 24674632
TI  - Models for count data with an application to Healthy Days measures: are you
      driving in screws with a hammer?
AB  - INTRODUCTION: Count data are often collected in chronic disease research, and
      sometimes these data have a skewed distribution. The number of unhealthy days
      reported in the Behavioral Risk Factor Surveillance System (BRFSS) is an example
      of such data: most respondents report zero days. Studies have either categorized
      the Healthy Days measure or used linear regression models. We used alternative
      regression models for these count data and examined the effect on statistical
      inference. METHODS: Using responses from participants aged 35 years or older from
      12 states that included a homeownership question in their 2009 BRFSS, we compared
      5 multivariate regression models--logistic, linear, Poisson, negative binomial,
      and zero-inflated negative binomial--with respect to 1) how well the modeled data
      fit the observed data and 2) how model selections affect inferences. RESULTS:
      Most respondents (66.8%) reported zero mentally unhealthy days. The distribution
      was highly skewed (variance = 58.7, mean = 3.3 d). Zero-inflated negative
      binomial regression provided the best-fitting model, followed by negative
      binomial regression. A significant independent association between homeownership
      and number of mentally unhealthy days was not found in the logistic, linear, or
      Poisson regression model but was found in the negative binomial model. The zero
      inflated negative binomial model showed that homeowners were 24% more likely than
      nonowners to have excess zero mentally unhealthy days (adjusted odds ratio, 1.24;
      95% confidence interval, 1.08-1.43), but it did not show an association between
      homeownership and the number of unhealthy days. CONCLUSION: Our comparison of
      regression models indicates the importance of examining data distribution and
      selecting models with appropriate assumptions. Otherwise, statistical inferences
      might be misleading.

PMID- 24674633
TI  - Prevalence of noncommunicable diseases and their risk factors in Guangzhou,
      China.
AB  - INTRODUCTION: This article reports on the prevalence of noncommunicable diseases
      (NCDs) and their risk factors in the city of Guangzhou, China, and shows a trend
      toward epidemic proportions when municipal data are compared with provincial
      data. METHODS: We conducted the Guangzhou Community Health Survey in the 12
      administrative districts of Guangzhou to learn about NCDs and their risk factors.
      A community-based, face-to-face survey with a stratified multistage cluster
      sampling was used. Information was gathered on 27,743 respondents, aged 0 to 108
      years, with a male to female ratio of 1 to 1. All participants completed a
      questionnaire, and those aged 15 years or older had a physical examination.
      Survey results were compared with the provincial results of the 2002 Guangdong
      Nutrition and Health Survey (GNHS). RESULTS: The data were weighted to the
      respondent's probability of selection and to the age- and sex-specific
      population. Prevalence estimate of self-reported NCDs was 16.0%. Hypertension and
      diabetes were reported as the most important NCDs. Of those who responded, 6.8%
      reported having more than 2 chronic conditions. The adjusted prevalence of
      hypertension decreased by 13.3% since 2002. Awareness, treatment, and control of
      hypertension and diabetes were improved. The estimated prevalence of current
      smoking decreased, and the prevalence of former smoking increased from 2002.
      However, the prevalence of overweight and obesity, especially central obesity,
      increased. CONCLUSION: Results were encouraging with regard to hypertension and
      diabetes. However, the unfavorable trends, especially for overweight, central
      obesity, and passive smoking, call for additional action.

PMID- 24674634
TI  - Program participation and blood pressure improvement in the Heart of New Ulm
      Project, Minnesota, 2009-2011.
AB  - INTRODUCTION: The Heart of New Ulm (HONU) Project is a community-based heart
      disease prevention intervention that delivers various component programs through
      health care, work sites, and the community. We examined the association between
      HONU program participation and blood pressure (BP) control over the first 2 years
      of the project. METHODS: The sample included residents aged 40 to 79 years from
      the target zip code who attended a heart health screening at baseline (2009) and
      again at follow-up (2011). BP control was defined as achieving or maintaining a
      BP less than 140/90 mm Hg in 2011. RESULTS: BP improvements were observed in the
      sample: 81.7% of those who had controlled BP in 2009 maintained controlled BP 2
      years later, and 52.4% of those with uncontrolled BP at baseline had controlled
      BP 2 years later (mean [SD] change in systolic BP, -10.6 mm Hg [20.8]). In the
      final adjusted model, participation in any 2 component programs of the HONU
      Project was associated with significantly higher odds of BP control among those
      with uncontrolled BP at baseline (n = 374). Participation in any component of the
      HONU Project among those with uncontrolled BP was associated with significant BP
      improvement compared with no participation. CONCLUSIONS: The clinical, work site,
      and community education and behavioral programs (eg, healthful diet or physical
      activity) delivered as part of a population-level heart disease prevention
      intervention were associated with meaningful BP improvements over 2 years among
      those with uncontrolled BP at baseline.

PMID- 24674635
TI  - Objective and self-reported factors associated with food-environment perceptions
      and fruit-and-vegetable consumption: a multilevel analysis.
AB  - INTRODUCTION: Few studies have assessed how people's perceptions of their
      neighborhood environment compare with objective measures or how self-reported and
      objective neighborhood measures relate to consumption of fruits and vegetables.
      METHODS: A telephone survey of 4,399 residents of Philadelphia, Pennsylvania,
      provided data on individuals, their households, their neighborhoods (self
      defined), their food-environment perceptions, and their fruit-and-vegetable
      consumption. Other data on neighborhoods (census tracts) or "extended
      neighborhoods" (census tracts plus 1-quarter-mile buffers) came from the US
      Census Bureau, the Philadelphia Police Department, the Southeastern Pennsylvania
      Transportation Authority, and the federal Supplemental Nutrition Assistance
      Program. Mixed-effects multilevel logistic regression models examined
      associations between food-environment perceptions, fruit-and-vegetable
      consumption, and individual, household, and neighborhood characteristics.
      RESULTS: Perceptions of neighborhood food environments (supermarket
      accessibility, produce availability, and grocery quality) were strongly
      associated with each other but not consistently or significantly associated with
      objective neighborhood measures or self-reported fruit-and-vegetable consumption.
      We found racial and educational disparities in fruit-and-vegetable consumption,
      even after adjusting for food-environment perceptions and individual, household,
      and neighborhood characteristics. Having a supermarket in the extended
      neighborhood was associated with better perceived supermarket access (adjusted
      odds ratio for having a conventional supermarket, 2.04 [95% CI, 1.68-2.46];
      adjusted odds ratio for having a limited-assortment supermarket, 1.28 [95% CI,
      1.02-1.59]) but not increased fruit-and-vegetable consumption. Models showed some
      counterintuitive associations with neighborhood crime and public transportation.
      CONCLUSION: We found limited association between objective and self-reported
      neighborhood measures. Sociodemographic differences in individual fruit-and
      vegetable consumption were evident regardless of neighborhood environment. Adding
      supermarkets to urban neighborhoods might improve residents' perceptions of
      supermarket accessibility but might not increase their fruit-and-vegetable
      consumption.

PMID- 24674636
TI  - Youth advocacy as a tool for environmental and policy changes that support
      physical activity and nutrition: an evaluation study in San Diego County.
AB  - BACKGROUND: As evidence grows about the benefits of policy and environmental
      changes to support active living and healthy eating, effective tools for
      implementing change must be developed. Youth advocacy, a successful strategy in
      the field of tobacco control, should be evaluated for its potential in the field
      of obesity prevention. COMMUNITY CONTEXT: San Diego State University collaborated
      with the San Diego County Childhood Obesity Initiative to evaluate Youth
      Engagement and Action for Health! (YEAH!), a youth advocacy project to engage
      youth and adult mentors in advocating for neighborhood improvements in physical
      activity and healthy eating opportunities. Study objectives included documenting
      group process and success of groups in engaging in community advocacy with
      decision makers. METHODS: In 2011 and 2012, YEAH! group leaders were recruited
      from the San Diego County Childhood Obesity Initiative's half-day train-the
      trainer seminars for adult leaders. Evaluators collected baseline and postproject
      survey data from youth participants and adult group leaders and interviewed
      decision makers. OUTCOMES: Of the 21 groups formed, 20 completed the evaluation,
      conducted community assessments, and advocated with decision makers. Various
      types of decision makers were engaged, including school principals, food service
      personnel, city council members, and parks and recreation officials. Eleven
      groups reported change(s) implemented as a result of their advocacy, 4 groups
      reported changes pending, and 5 groups reported no change as a result of their
      efforts. INTERPRETATION: Even a brief training session, paired with a practical
      manual, technical assistance, and commitment of adult leaders and youth may
      successfully engage decision makers and, ultimately, bring about change.

PMID- 24674637
TI  - Effect of light touch on postural sway in individuals with balance problems: a
      systematic review.
AB  - The aim of the present review was to examine the experimental, case-control
      studies that investigated the effect of light touch on postural sway in
      individuals with balance problems due to aging, brain lesion or other motor or
      sensory deficits. Articles published before the end of March of 2013 were
      searched in PubMed, Scielo and Lilacs databases using terms related to postural
      control and sensory information. Twelve studies that assessed the postural sway
      of individuals with balance problems during quiet standing with the light touch
      using a force plate were reviewed. Two reviewers rated all selected articles as
      having good quality. The effect of light touch on postural control was reported
      by all eligible studies regardless of the cause of the balance problem of the
      participants. Such effect was more evident when the applied vertical force was
      greater than 1N, but if individuals with poor balance took more advantage of the
      light touch than healthy ones it depended on the source of their balance problems
      and not the amount of the applied force. These findings suggested that the
      maintenance of the fingertip lightly touching an external surface could provide
      additional somatosensory information for individuals with poor balance and then
      it could be used as a strategy to improve the control of upright standing during
      intervention programs. 

PMID- 24674638
TI  - Bone densitometry in infants and young children: the 2013 ISCD Pediatric Official
      Positions.
AB  - Infants and children <5 yr were not included in the 2007 International Society
      for Clinical Densitometry Official Positions regarding Skeletal Health Assessment
      of Children and Adolescents. To advance clinical care of very young children, the
      International Society for Clinical Densitometry 2013 Position Development
      Conference reviewed the literature addressing appropriate methods and skeletal
      sites for clinical dual-energy X-ray absorptiometry (DXA) measurements in infants
      and young children and how results should be reported. DXA whole-body bone
      mineral content and bone mineral density for children >=3 yr and DXA lumbar spine
      measurements for infants and young children 0-5 yr were identified as feasible
      and reproducible. There was insufficient information regarding methodology,
      reproducibility, and reference data to recommended forearm and femur measurements
      at this time. Appropriate methods to account for growth delay when interpreting
      DXA results for children <5 yr are currently unknown. Reference data for children
      0-5 yr at multiple skeletal sites are insufficient and are needed to enable
      interpretation of DXA measurements. Given the current scarcity of evidence in
      many areas, it is likely that these positions will change over time as new data
      become available. 

PMID- 24674639
TI  - Maximal oxygen consumption and bone mineral density in a group of young Lebanese
      adults.
AB  - The aim of this study was to explore the relationship between maximal oxygen
      consumption (VO2 max) and bone mineral density (BMD) in a group of young Lebanese
      adults. Twenty women and 37 men whose ages range from 18 to 32 yr participated in
      this study. Informed written consent was obtained from the participants. Body
      weight and height were measured, and body mass index was calculated. VO2 max was
      determined by direct measurement while exercising on a bicycle ergometer (Siemens
      Elema RE 820; Rodby Elektronik AB, Enhorna, Sweden). Whole body bone mineral
      content (WB BMC), whole body bone mineral density (WB BMD), lumbar spine BMD (L1
      L4 BMD), total hip BMD (TH BMD), and femoral neck BMD (FN BMD) were measured by
      dual-energy X-ray absorptiometry. In women, VO2 max (expressed as L/mn) was
      positively correlated to WB BMC (r = 0.82; p < 0.001), WB BMD (r = 0.80; p <
      0.001), L1-L4 BMD (r = 0.73; p < 0.001), TH BMD (r = 0.80; p < 0.001), and FN BMD
      (r = 0.85; p < 0.001). In men, VO2 max (expressed as L/mn) was positively
      correlated to WB BMC (r = 0.57; p < 0.001), WB BMD (r = 0.53; p < 0.001), L1-L4
      BMD (r = 0.50; p < 0.001), TH BMD (r = 0.38; p < 0.01), and FN BMD (r = 0.30; p <
      0.05). In both sexes, the positive associations between VO2 max and bone
      variables (BMC and BMD) remained significant after adjustment for age (p <
      0.001). This study suggests that VO2 max (L/mn) is a positive determinant of BMC
      and BMD in young adults. Aerobic power seems to be a determinant of BMC and BMD
      in young adults. 

PMID- 24674641
TI  - Evaluation of ionic liquids-coated carbon nanotubes modified chiral separation
      system with chondroitin sulfate E as chiral selector in capillary
      electrophoresis.
AB  - Nanoparticles (NPs) and ionic liquids (ILs) have been extensively studied and
      have aroused considerable interest in separation science; however, the employment
      of ILs-dispersed NPs as buffer modifiers for CE chiral separation has not been
      previously studied. In this work, we describe a new CE method using ILs dispersed
      multi-walled carbon nanotubes (ILs-MWNTs) as a modifier for enantioseparation
      with a polysaccharide, chondroitin sulfate E (CSE), as the chiral selector. As
      observed, significantly improved separations, including better enantioselectivity
      and improved peak shapes, were obtained in the ILs-MWNTs modified separation
      system for all drug enantiomers compared to the single CSE system. Several
      parameters affecting the enantioseparation, such as the choice of ILs and carbon
      nanoparticles, ILs-MWNTs concentration, chiral selector concentration, buffer pH
      and applied voltage, were systematically investigated. Satisfactory separations
      were achieved when 2.4MUg/mL ILs-MWNTs were introduced into the 20mM Tris/H3PO4
      buffer solution containing 2.5% CSE at pH 2.8-3.4 with a 15kV applied voltage. A
      brief mechanism of the enhanced enantioseparation capability of the ILs-MWNTs
      modified chiral separation system was also discussed. 

PMID- 24674642
TI  - A low pressure on-chip injection strategy for high-performance chip-based
      chromatography.
AB  - A microfluidic device for high-performance liquid chromatography is presented.
      The borosilicate glass chip includes a common cross-channel injector and a column
      chamber. The column chamber comprises two constrictions (10 MUm) to retain the
      chromatographic particles via the keystone effect. A packing channel was utilized
      to introduce the particulate material (3-MUm). This channel has been sealed
      permanently via laser-assisted photopolymerization avoiding dead volumes within
      the chromatographic pathway. A sampling strategy is presented enabling the
      directed definition of the sample plug on-chip. The injection process is studied
      via video microscopy and chromatographic separations of test solutes with
      fluorescence detection. Our approach, based on on-chip flow splitting, allows the
      usage of traditional, economic and robust HPLC instrumentation avoiding the need
      for sophisticated nano-flow equipment. The performance of the chip device and the
      injection process was demonstrated by reversed-phase chromatographic separations
      of a mixture of polycyclic aromatic hydrocarbons achieving constant high
      efficiencies for the chromatographic signals over the whole elution window.

PMID- 24674643
TI  - Hydrodynamic chromatography and field flow fractionation in finite aspect ratio
      channels.
AB  - Hydrodynamic chromatography (HC) and field-flow fractionation (FFF) separation
      methods are often performed in 3D rectangular channels, though ideal retention
      theory assumes 2D systems. Devices are commonly designed with large aspect
      ratios; however, it can be unavoidable or desirable to design rectangular
      channels with small or even near-unity aspect ratios. To assess the significance
      of finite-aspect ratio effects and interpret experimental retention results, an
      ideal, analytical retention theory is needed. We derive a series solution for the
      ideal retention ratio of HC and FFF rectangular channels. Rather than limiting
      devices' ability to resolve samples, our theory predicts that retention curves
      for normal-mode FFF are well approximated by the infinite plate solution and that
      the performance of HC is actually improved. These findings suggest that FFF
      devices need not be designed with large aspect ratios and that rectangular HC
      channels are optimal when the aspect ratio is unity. 

PMID- 24674644
TI  - Use of electron ionization and atmospheric pressure chemical ionization in gas
      chromatography coupled to time-of-flight mass spectrometry for screening and
      identification of organic pollutants in waters.
AB  - A new approach has been developed for multiclass screening of organic
      contaminants in water based on the use of gas chromatography coupled to hybrid
      quadrupole high-resolution time-of-flight mass spectrometry with atmospheric
      pressure chemical ionization (GC-(APCI)QTOF MS). The soft ionization promoted by
      the APCI source allows effective and wide-scope screening based on the
      investigation of the molecular ion and/or protonated molecule. This is in
      contrast to electron ionization (EI) where ionization typically results in
      extensive fragmentation, and diagnostic ions and/or spectra need to be known a
      priori to facilitate detection of the analytes in the raw data. Around 170
      organic contaminants from different chemical families were initially investigated
      by both approaches, i.e. GC-(EI)TOF and GC-(APCI)QTOF, including polycyclic
      aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated
      diphenyl ethers (PBDEs) and a notable number of pesticides and relevant
      metabolites. The new GC-(APCI)QTOF MS approach easily allowed widening the number
      of compounds investigated (85 additional compounds), with more pesticides,
      personal care products (UV filters, musks), polychloronaphthalenes (PCNs),
      antimicrobials, insect repellents, etc., most of them considered as emerging
      contaminants. Both GC-(EI)TOF and GC-(APCI)QTOF methodologies have been applied,
      evaluating their potential for a wide-scope screening in the environmental field.

PMID- 24674645
TI  - Diversity and stability of cultured vaginal lactobacilli in pregnant women from a
      multi-ethnic urban UK population.
AB  - AIM: To determine the diversity and stability of cultured vaginal lactobacilli in
      a multi-ethnic population of pregnant women. METHODS AND RESULTS: A single
      centre, prospective, cohort study was performed in a tertiary perinatal centre in
      East London, UK. Self-collected vaginal swabs at 13 and 20 weeks gestation were
      obtained from women attending for routine antenatal care and cultured for
      lactobacilli. In women who provided both swabs, 37 of 203 (18%) had no
      lactobacilli cultured at either time. Only 53 (26%) had the same species at both
      times. Black women were less likely to have lactobacilli cultured at 13 weeks (P
      = 0.014), and Black and Asian women were less likely to have lactobacilli
      cultured at 20 weeks (P = 0.002) compared with those in the White and Other
      groups. CONCLUSIONS: Significant differences exist between ethnic groups in the
      carriage and stability of vaginal lactobacilli. SIGNIFICANCE AND IMPACT OF THE
      STUDY: These differences have implications for the design of interventions aimed
      at normalizing the vaginal microbiota in pregnant women.

PMID- 24674646
TI  - Synthesis and anti-HIV activity of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3
      hydroxyl derivatives.
AB  - A series of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3-hydroxyl derivatives (Ia-Im
      and IIa-IIe) designed as novel HIV-1 non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) was synthesized via an expeditious route and evaluated for
      their anti-HIV activities in MT-4 cell cultures. All the synthesized compounds
      were structurally confirmed by spectral analyses. Biological results showed that
      three analogues displayed moderate inhibitory activity against wild-type (wt) HIV
      1 replication with EC(50) values ranging from 16 to 22 MUm. Molecular docking of
      compound Ih with wt HIV-1 RT was performed to understand the binding mode between
      these inhibitors and the wt HIV-1 RT and to rationalize some SARs.

PMID- 24674647
TI  - Children's perceived emotional behavior at disclosure and prosecutors'
      evaluations.
AB  - The present study investigated the perceived emotional behavior of alleged child
      victims when disclosing sexual abuse in a forensic interview. It also addressed
      whether the perceived emotional behavior influenced prosecutors' evaluations of
      children's potential as witnesses and prosecutors' recommendations to press
      charges. Ninety-eight videotapes of forensic interviews with alleged child sexual
      abuse victims (4- to 17-year-olds) were coded for behavioral indicators of
      emotions. Case file information and district attorney evaluations were also
      coded. Results indicated that children were not generally perceived as being
      emotional (e.g., sad) during disclosure. However, the perceived intensity of
      expressed emotions was greater when children disclosed the alleged abuse compared
      to when they discussed more neutral topics in rapport building. Greater perceived
      emotional withdrawal by children at disclosure was associated with more negative
      evaluations of child witnesses by prosecutors. Moreover, children's emotional
      behaviors, as noted by prosecutors, were among the predictors of prosecutors'
      recommendations to file charges. Practical implications are discussed. 

PMID- 24674648
TI  - Stakeholder views on the incorporation of traditional birth attendants into the
      formal health systems of low-and middle-income countries: a qualitative analysis
      of the HIFA2015 and CHILD2015 email discussion forums.
AB  - BACKGROUND: Health workforce shortages are key obstacles to the achievement of
      the health-related Millennium Development Goals. Task shifting is seen as a way
      to improve access to pregnancy and childbirth care. However, the role of
      traditional birth attendants (TBAs) within task shifting initiatives remains
      contested. The objective of this study was to explore stakeholder views and
      justifications regarding the incorporation of TBAs into formal health systems.
      METHODS: Data were drawn from messages submitted to the HIFA2015 and CHILD2015
      email discussion forums. The forums focus on the healthcare information needs of
      frontline health workers and citizens in low - and middle-income countries, and
      how these needs can be met, and also include discussion of diverse aspects of
      health systems. Messages about TBAs submitted between 2007-2011 were analysed
      thematically. RESULTS: We identified 658 messages about TBAs from a total of 193
      participants. Most participants supported the incorporation of trained TBAs into
      primary care systems to some degree, although their justifications for doing so
      varied. Participant viewpoints were influenced by the degree to which TBA
      involvement was seen as a long-term or short-term solution and by the tasks
      undertaken by TBAs. CONCLUSIONS: Many forum members indicated that they were
      supportive of trained TBAs being involved in the provision of pregnancy care.
      Members noted that TBAs were already frequently used by women and that
      alternative options were lacking. However, a substantial minority regarded doing
      so as a threat to the quality and equity of healthcare. The extent of TBA
      involvement needs to be context-specific and should be based on evidence on
      effectiveness as well as evidence on need, acceptability and feasibility.

PMID- 24674649
TI  - Contemporary evolution of an invasive grass in response to elevated atmospheric
      CO(2) at a Mojave Desert FACE site.
AB  - Elevated atmospheric CO2 has been shown to rapidly alter plant physiology and
      ecosystem productivity, but contemporary evolutionary responses to increased CO2
      have yet to be demonstrated in the field. At a Mojave Desert FACE (free-air CO2
      enrichment) facility, we tested whether an annual grass weed (Bromus madritensis
      ssp. rubens) has evolved in response to elevated atmospheric CO2 . Within 7
      years, field populations exposed to elevated CO2 evolved lower rates of leaf
      stomatal conductance; a physiological adaptation known to conserve water in other
      desert or water-limited ecosystems. Evolution of lower conductance was
      accompanied by reduced plasticity in upregulating conductance when CO2 was more
      limiting; this reduction in conductance plasticity suggests that genetic
      assimilation may be ongoing. Reproductive fitness costs associated with this
      reduction in phenotypic plasticity were demonstrated under ambient levels of CO2
      . Our findings suggest that contemporary evolution may facilitate this invasive
      species' spread in this desert ecosystem.

PMID- 24674650
TI  - Successful treatment of iatrogenic multicentric Castleman's disease arising due
      to recrudescence of HHV-8 in a liver transplant patient.
AB  - We describe the case of a 59-year-old HIV-negative male who developed
      multicentric Castleman's disease (MCD) 1 year postliver transplantation due to
      recrudescence of a pretransplant human herpesvirus-8 (HHV-8) infection. He
      presented with fevers, dry cough, weight loss and drenching night sweats. Routine
      investigations were all unremarkable. Computerized axial tomography (CT) scans
      showed splenomegaly and intra-abdominal lymphadenopathy, confirmed by positron
      emission tomography. Cervical lymph node biopsies were consistent with MCD. The
      presence of HHV-8 was confirmed on immunohistochemistry. Peripheral blood HHV-8
      quantitative polymerase chain reaction (qPCR) monitoring showed a threefold
      decrease in viremia in the first week of treatment with ganciclovir but had
      little impact on clinical symptoms. Reducing immunosuppression and switching to
      rituximab resolved clinical symptoms and produced a negative HHV-8 qPCR result.
      Retrospective molecular testing of sera collected pre- and immediately
      posttransplantation confirmed preexisting HHV-8 in the host. This is the first
      reported case of an HIV-negative postliver transplant patient developing MCD that
      manifested as posttransplant lymphoproliferative disorder due to recrudescence of
      HHV-8. We propose (1) the introduction of the term iatrogenic Castleman's disease
      (CD) for this and similar cases, (2) rituximab should be considered as a
      treatment option for CD and (3) consideration be given to a change to the World
      Health Organization classification of CD to incorporate such cases. 

PMID- 24674651
TI  - Chromoendoscopy associated with endoscopic laryngeal surgery: a new technique for
      treating recurrent respiratory papillomatosis.
AB  - OUTLINE: Chromoendoscopy is a dye enhancement technique that uses epithelial
      tissue dyeing for assessing any changes in it by determining its characteristics
      and eventually to improving mucosal lesions detection at endoscopy. Currently
      with the addition of a joint use of rigid endoscopes and video systems at
      surgery, visualization of the larynx and trachea areas significantly improved
      with wide angle viewing. However, in certain diseases, such as laryngeal
      papillomatosis, certain conditions were overlooked by these approaches and with
      the likelihood of postoperative early relapse. With the addition of
      chromoendoscopy to endoscopic laryngeal surgery, we were able to increase the
      ability to recognize intraoperatively inconspicuous lesions, improve lesion limit
      visualization, observe in detail their surfaces, and determine as well the
      existence of residual lesion if any after surgical removal. OBJECTIVES: To prove
      the helpfulness of chromoendoscopy in otolaryngology as an innovative diagnostic
      technique associated with laryngeal endoscopical surgery. MATERIALS AND METHODS:
      The present study uses contrast dyeing agents such as indigo carmine as
      endoscopic tissue staining and, incidentally, which is the most widely used
      detection method in gastroenterology. The dye fills the interstices, highlighting
      irregularities, such as depressions and elevations in architecture. RESULTS: This
      diagnostic enhancing technique was used with six patients who presented recurrent
      laryngeal papillomatosis. We committed ourselves to get the most out of the
      intraoperative diagnostic yield and reduce the relapse likelihoods in all cases.
      CONCLUSION: Chromoendoscopy joined with endoscopic laryngeal surgery is an
      excellent intraoperative diagnostic approach in the management of laryngeal
      invasive conditions such as laryngeal papillomatosis.

PMID- 24674652
TI  - Intra-articular metastatic pancreatic carcinoma of the right knee mimicking
      septic arthritis.

PMID- 24674653
TI  - Tracking changes in states of contraceptive use over time in sub-Saharan Africa
      through cohort and period analyses.
AB  - It is difficult to gauge the success of programmatic efforts to reduce unmet need
      for contraception without knowing whether individual women have had their need
      met and adopted contraception. However, the number of true longitudinal datasets
      tracking the transition of panels of individual women in and out of states of
      contraceptive use is limited. This study analyses changes in contraceptive use
      states using Demographic and Health Survey data for 22 sub-Saharan African
      countries. A cohort approach, tracking representative samples of five-year age
      groups longitudinally across surveys, as well as period-based techniques, are
      applied to indicate whether new users of contraception have been drawn from women
      who previously had no need and/or those who had unmet need for family planning.
      The results suggest that a greater proportion of increases in contraceptive use
      in recent years can be attributed to decreases in the percentage of women with no
      need, especially among younger women, than to decreases in the proportion with
      unmet need. 

PMID- 24674655
TI  - Impact of surgeon volume on the morbidity and costs of radical cystectomy in the
      USA: a contemporary population-based analysis.
AB  - OBJECTIVES: To evaluate the relationship between surgeon volume of radical
      cystectomy (RC) and postoperative morbidity, and to assess the economic burden of
      bladder cancer in the USA. METHODS: We captured all patients who underwent RC
      (International Classification of Diseases, ninth revision, code 57.71) between
      2003 and 2010, using a nationwide hospital discharge database. Patient, hospital
      and surgical characteristics were evaluated. The annual volume of RCs performed
      by the surgeons was divided into quintiles. Multivariable regression models were
      developed, adjusting for clustering and survey weighting, to evaluate the
      outcomes, including 90-day major complications (Clavien grade III-V) and direct
      patient costs. We adjusted for clustering and weighting to achieve a nationally
      representative analysis. RESULTS: The weighted cohort included 49,792 patients
      who underwent RC, with an overall 90-day major complication rate of 16.2%.
      Compared with surgeons performing one RC annually, surgeons performing >=7 RCs
      each year had 45% lower odds of major complications (odds ratio [OR] 0.55; P <
      0.001) and lower costs by $1690 (P = 0.02). Results were consistent when we
      analysed surgeon volume as a continuous variable and when we examined the
      surgeons with the highest volumes (>=28 cases annually), which showed markedly
      lower odds of major complications compared with the surgeons with the lowest
      volumes (OR 0.45, 95% CI 0.31-0.67; P < 0.001). Compared with patients who did
      not have any complications, those who had a major complication were associated
      with significantly higher 90-day median direct hospital costs ($43,965 vs
      $24,341; P < 0.001). CONCLUSIONS: We showed that there was an inverse
      relationship between surgeon volume and the development of postoperative 90-day
      major complication rates as well as direct hospital costs. Centralisation of RC
      to surgeons with higher volumes may reduce the development of postoperative major
      complications, thereby decreasing the burden of bladder cancer on the healthcare
      system.

PMID- 24674654
TI  - Impact of age of first exposure to Plasmodium falciparum on antibody responses to
      malaria in children: a randomized, controlled trial in Mozambique.
AB  - BACKGROUND: The impact of the age of first Plasmodium falciparum infection on the
      rate of acquisition of immunity to malaria and on the immune correlates of
      protection has proven difficult to elucidate. A randomized, double-blind, placebo
      controlled trial using monthly chemoprophylaxis with sulphadoxine-pyrimethamine
      plus artesunate was conducted to modify the age of first P. falciparum
      erythrocytic exposure in infancy and assess antibodies and malaria risk over two
      years. METHODS: Participants (n = 349) were enrolled at birth to one of three
      groups: late exposure, early exposure and control group, and were followed up for
      malaria morbidity and immunological analyses at birth, 2.5, 5.5, 10.5, 15 and 24
      months of age. Total IgG, IgG subclasses and IgM responses to MSP-1(19), AMA-1,
      and EBA-175 were measured by ELISA, and IgG against variant antigens on the
      surface of infected erythrocytes by flow cytometry. Factors affecting antibody
      responses in relation to chemoprophylaxis and malaria incidence were evaluated.
      RESULTS: Generally, antibody responses did not vary significantly between
      exposure groups except for levels of IgM to EBA-175, and seropositivity of IgG1
      and IgG3 to MSP-1(19). Previous and current malaria infections were strongly
      associated with increased IgG against MSP-1(19), EBA-175 and AMA-1 (p < 0.0001).
      After adjusting for exposure, only higher levels of anti-EBA-175 IgG were
      significantly associated with reduced clinical malaria incidence (IRR 0.67, p =
      0.0178). CONCLUSIONS: Overall, the age of first P. falciparum infection did not
      influence the magnitude and breadth of IgG responses, but previous exposure was
      critical for antibody acquisition. IgG responses to EBA-175 were the strongest
      correlate of protection against clinical malaria. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00231452.

PMID- 24674657
TI  - [Pathologie Biologie, 60 years already!].

PMID- 24674656
TI  - Hydrodynamic lift of vesicles and red blood cells in flow--from Fahraeus &
      Lindqvist to microfluidic cell sorting.
AB  - Hydrodynamic lift forces acting on cells and particles in fluid flow receive
      ongoing attention from medicine, mathematics, physics and engineering. The early
      findings of Fahraeus & Lindqvist on the viscosity change of blood with the
      diameter of capillaries motivated extensive studies both experimentally and
      theoretically to illuminate the underlying physics. We review this historical
      development that led to the discovery of the inertial and non-inertial lift
      forces and elucidate the origins of these forces that are still not entirely
      clear. Exploiting microfluidic techniques induced a tremendous amount of new
      insights especially into the more complex interactions between the flow field and
      deformable objects like vesicles or red blood cells. We trace the way from the
      investigation of single cell dynamics to the recent developments of microfluidic
      techniques for particle and cell sorting using hydrodynamic forces. Such
      continuous and label-free on-chip cell sorting devices promise to revolutionize
      medical analyses for personalized point-of-care diagnosis. We present the state
      of-the-art of different hydrodynamic lift-based techniques and discuss their
      advantages and limitations. 

PMID- 24674658
TI  - Conformational and thermal characterization of a synthetic peptidic fragment
      inspired from human tropoelastin: Signature of the amyloid fibers.
AB  - OBJECTIVES: This work deals with the conformational and thermal characterization
      of a synthetic peptide (S4) released during the proteolysis of human tropoelastin
      by the matrix metalloproteinase-12 that was shown to form amyloid-like fibres
      under certain conditions. MATERIALS AND METHODS: S4 peptides were synthesized by
      solid-phase methodology and aggregated in solution at 80 degrees C. Fourier
      transform-infrared spectroscopy (FT-IR) was used to access the secondary
      structure. Thermal characterization was performed by thermogravimetric analysis
      (TGA) and differential scanning calorimetry (DSC). RESULTS: The DSC study of the
      soluble linear peptide S4 in solution in TBS reveals the irreversible aggregation
      into amyloid fibres. FT-IR, DSC and TGA analyses performed on freeze-dried
      samples evidence differences between the linear peptide and its associated
      amyloid-like fibres, both on the conformation and the physical structure. When S4
      peptides are aggregated, the prominent conformation scanned by FT-IR is the cross
      beta-structure, corresponding to TGA to an increase of the thermal stability.
      Moreover, the DSC thermograms of S4 fibres are characteristic of a highly ordered
      structure, in contrast to the DSC thermograms of S4 linear peptides,
      characteristic of an amorphous structure. Finally, the DSC analysis of
      differently hydrated S4 fibres brings to the fore the specific thermal answer of
      the wet interfaces of the cross beta-fibres. CONCLUSION: FT-IR and thermal
      techniques are well suited to evidence conformational and structural differences
      between the soluble peptide and its amyloid form.

PMID- 24674660
TI  - Menage a trois: an evolutionary interplay between human papillomavirus, a tumor,
      and a woman.
AB  - Cervical cancer is the third most common cancer in women with human
      papillomavirus (HPV) being a key etiologic factor of this devastating disease. In
      this article, we describe modern advances in the genomics and transcriptomics of
      cervical cancer that led to uncovering the key gene drivers. We also introduce,
      herein, a model of cervical carcinogenesis that explains how the interplay
      between virus, tumor, and woman results in the selection of clones that
      simultaneously harbor genomic amplifications for genes that drive cell cycle,
      antiviral response, and inhibit cell differentiation. The new model may help
      researchers understand the controversies in antiviral therapy and immunogenetics
      of this cancer and may provide a basis for future research directions in early
      diagnostics and personalization of therapy. 

PMID- 24674659
TI  - High cytochrome c oxidase expression links to severe skeletal energy failure by
      (31)P-MRS spectroscopy in mitochondrial encephalomyopathy, lactic acidosis, and
      stroke-like episodes.
AB  - AIMS: The purpose of this study was to evaluate the energy metabolism and
      mitochondrial function in skeletal muscle from patients with Mitochondrial
      encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) or chronic
      progressive external ophthalmoplegia (CPEO) using phosphorus magnetic resonance
      spectroscopy ((31)P-MRS), to determine whether abnormally increasing cytochrome c
      oxidase (COX), as detected in muscle biopsy, could be a cause for MELAS. METHODS:
      (31)P-MRS was performed on the quadriceps femoris muscle of 12 healthy volunteers
      and 11 patients diagnosed as MELAS or CPEO by muscle biopsy and genetic analysis.
      All subjects experienced a state of rest, 5-min exercise, and 5-min recovery
      protocol in a supine position. RESULTS: Compared to CPEO, MELAS patients
      typically exhibited COX-positive ragged-red fibers (RRFs) as well as strongly SDH
      positive blood vessels (SSVs). However, based on (31)P-MRS results, MELAS showed
      a higher inorganic phosphate (Pi)/phosphocreatine (PCr) ratio and lower ATP/PCr
      ratio during exercise and delayed Pi/PCr and ATP/PCr recovery to normal.
      CONCLUSIONS: This study suggests that high COX expression contributes to severe
      skeletal energy failure by (31)P-MRS spectroscopy in MELAS.

PMID- 24674662
TI  - Exploring the risk factors for vaccine-associated and non-vaccine associated
      febrile seizures in a large pediatric cohort.
AB  - INTRODUCTION: It is not known whether there are underlying physiologic or
      immunologic differences between febrile seizures (FS) triggered by vaccines
      versus other causes. Furthermore, while secular and individual-level factors have
      been associated with FS risk, they are rarely evaluated simultaneously. METHODS:
      Subjects included members of Kaiser Permanente Southern California aged 6 months
      to 3 years from July 1, 2003-December 31, 2011. Primary outcome was first
      diagnosis of FS. Vaccine-associated (VA) FS were defined as those occurring from
      day 0 to day 15 following any vaccine; non-vaccine associated (NVA) FS were those
      outside this period. We compared incidence rates of VA-FS versus NVA-FS. Poisson
      regression was used to assess the association between FS and secular and
      individual-level factors. We also evaluated interactions between vaccine exposure
      and each model covariate on the risk of FS. RESULTS: Among 265,275 children, 3348
      FS were identified; 383(11%) were VA-FS, and 2965(89%) were NVA-FS. Incidence
      rates were 2.73 and 2.05 per 100,000 person-days for VA-FS and NVA-FS,
      respectively. Multivariable analyses confirmed previously reported increased risk
      of FS by age, low gestational age, and winter months. Increased risk was also
      associated with VA exposure (RR=1.63[95% CI: 1.27-2.11]), non-White
      race/ethnicity vs. White (African-American RR=1.41[1.22-1.63]; Asian RR=1.58[1.40
      1.79]; Hispanic RR=1.60[1.47-1.75]), and maternal age 29 years or less vs. 40+
      years (<= 19 years RR=1.28[1.00-1.65]; 20-29 years RR=1.21[1.02-1.42]). Females
      were at lower risk of NVA-FS (RR=0.77[0.72-0.83]), but were similar to males for
      VA-FS (RR=0.97[0.79-1.19]). Children with low 1 min Apgar scores (<= 3) had
      increased risk of VA-FS (RR=3.40[1.86-6.22]), but no increased risk for NVA-FS
      (RR=1.05[0.69-1.60]) compared to children with normal Apgar scores (>= 7).
      DISCUSSION: This study suggests that there may be immunogenetic differences
      underlying VA-FSs compared with other FSs. However, further studies are needed.
      An understanding of the mechanisms behind these findings may help improve vaccine
      design or policies.

PMID- 24674661
TI  - Reduced incidence of invasive pneumococcal disease after introduction of the 13
      valent conjugate vaccine in Navarre, Spain, 2001-2013.
AB  - Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and
      became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and
      2010 (PCV13). This study evaluates changes in the incidence of invasive
      pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre,
      Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010
      2013). The percentage of children <2 years who received at least one dose of PCV
      in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the
      periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4
      cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69%
      (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those >= 65, by
      23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81%
      (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No
      significant changes were seen in the distribution of clinical presentations or in
      disease severity. The incidence of IPD has declined and the pattern of serotypes
      causing IPD has changed notably in children and moderately in adults following
      the replacement of PCV7 by PCV13.

PMID- 24674664
TI  - A model for early onset of protection against lethal challenge with highly
      pathogenic H5N1 influenza virus.
AB  - Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause
      severe disease in humans and involve the risk of inducing a pandemic by gaining
      the ability for human-to-human transmission. In naive poultry, primarily
      gallinaceous birds, the virus induces fatal disease and the used inactivated
      vaccines occasionally are unable to provide efficient and early onset of
      protection. Therefore, optimized vaccines must be developed and evaluated in
      model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza
      A virus variant to analyze the induction of a very early onset of immunity.
      Ferrets, mice and chickens were each immunized with a single vaccine dose seven,
      three and one day before lethal challenge infection, respectively. Sound
      protection was conferred in 100% of animals immunized seven days prior to
      challenge infection. In these animals, no clinical signs were observed, and no
      challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal
      washings, and organ samples. Moreover, the attenuated modified-live virus variant
      protected all chickens, mice, and ferrets as early as three days after
      vaccination against severe clinical signs. Chickens and ferrets developed
      hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific
      antibodies, making this kind of neuraminidase-negative strain suitable for the
      DIVA ("differentiating vaccinated from infected animals") strategy. 

PMID- 24674663
TI  - Effects of varying antigens and adjuvant systems on the immunogenicity and safety
      of investigational tetravalent human oncogenic papillomavirus vaccines: results
      from two randomized trials.
AB  - BACKGROUND: A prophylactic human papillomavirus (HPV) vaccine targeting oncogenic
      HPV types in addition to HPV-16 and -18 may broaden protection against cervical
      cancer. Two Phase I/II, randomized, controlled studies were conducted to compare
      the immunogenicity and safety of investigational tetravalent HPV L1 virus-like
      particle (VLP) vaccines, containing VLPs from two additional oncogenic genotypes,
      with the licensed HPV-16/18 AS04-adjuvanted vaccine (control) in healthy 18-25
      year-old women. METHODS: In one trial (NCT00231413), subjects received control or
      one of 6 tetravalent HPV-16/18/31/45 AS04 vaccine formulations at months (M)
      0,1,6. In a second trial (NCT00478621), subjects received control or one of 5
      tetravalent HPV-16/18/33/58 vaccines formulated with different adjuvant systems
      (AS04, AS01 or AS02), administered on different schedules (M0,1,6 or M0,3 or
      M0,6). RESULTS: One month after the third injection (Month 7), there was a
      consistent trend for lower anti-HPV-16 and -18 geometric mean antibody titers
      (GMTs) for tetravalent AS04-adjuvanted vaccines compared with control. GMTs were
      statistically significantly lower for an HPV-16/18/31/45 AS04 vaccine containing
      20/20/10/10 MUg VLPs for both anti-HPV-16 and anti-HPV-18 antibodies, and for an
      HPV-16/18/33/58 AS04 vaccine containing 20/20/20/20 MUg VLPs for anti-HPV-16
      antibodies. There was also a trend for lower HPV-16 and -18-specific memory B
      cell responses for tetravalent AS04 vaccines versus control. No such trends were
      observed for CD4(+) T-cell responses. Immune interference could not always be
      overcome by increasing the dose of HPV-16/18 L1 VLPs or by using a different
      adjuvant system. All formulations had acceptable reactogenicity and safety
      profiles. Reactogenicity in the 7-day post-vaccination period tended to increase
      with the introduction of additional VLPs, especially for formulations containing
      AS01. CONCLUSIONS: HPV-16 and -18 antibody responses were lower when additional
      HPV L1 VLPs were added to the HPV-16/18 AS04-adjuvanted vaccine. Immune
      interference is a complex phenomenon that cannot always be overcome by changing
      the antigen dose or adjuvant system.

PMID- 24674665
TI  - Heat treatment improves antigen-specific T cell activation after protein delivery
      by several but not all yeast genera.
AB  - A central prerequisite in using yeast as antigen carrier in vaccination is its
      efficient interaction with cellular components of the innate immune system,
      mainly mediated by cell surface structures. Here, we investigated the
      distribution of major yeast cell wall components such as mannan, beta-glucan and
      chitin of four different and likewise biotechnologically relevant yeasts
      (Saccharomyces, Pichia, Kluyveromyces and Schizosaccharomyces) and analyzed the
      influence of heat-treatment on beta-1,3-glucan exposure at the outer yeast cell
      surface as well as the amount of yeast induced reactive oxygen species (ROS)
      production by antigen presenting cells (APC) in human blood. We found that yeasts
      significantly differ in the distribution of their cell wall components and that
      heat-treatment affected both, cell wall composition and yeast-induced ROS
      production by human APCs. We further show that heat-treatment modulates the
      activation of antigen specific memory T cells after yeast-mediated protein
      delivery in different ways and thus provide additional support of using yeast as
      vehicle for the development of novel T cell vaccines. 

PMID- 24674666
TI  - A pragmatic comparison of two diabetes education programs in improving type 2
      diabetes mellitus outcomes.
AB  - BACKGROUND: Although it is clear that education programs constitute key elements
      of improved diabetes management, uncertainty exists regarding the optimal method
      of delivering that education. In addition to the lack of consensus regarding the
      most appropriate delivery methods for these programs, there is a paucity of
      research which evaluates these methods in terms of specific clinical outcomes.
      This pragmatic study compares the effectiveness of two distinct diabetes
      education programs in improving clinical outcomes in patients with type 2
      diabetes mellitus in a primary care setting. RESULTS: The two diabetes education
      classes (n = 80 enrolled) retrospectively evaluated were 'the ABC's of Diabetes'
      (one 2-hour didactic teaching session) and 'Conversation Maps' (3 highly
      interactive weekly classes, 6 hours in total). Eligible participants (n = 32) had
      their charts reviewed and outcome measures (i.e., glycosylated hemoglobin levels
      (HbA1c), low density lipoprotein (LDL), systolic blood pressure (SBP), diastolic
      blood pressure (DBP), and weight) recorded 1 year prior to and 6 months following
      the class. Pre- and post-class outcome measures were compared. A trend towards
      lower HbA1c was observed after completion of both classes, with an average
      reduction of 0.2%, and 0.6% after 6 months in the 'ABC's of Diabetes' class and
      'Conversation Maps' class respectively. A significant decrease in weight was
      observed 6 months after the 'ABC's of Diabetes' class (p = 0.028), and in LDL
      after the 'Conversation Maps' class (p = 0.049). Patients with HbA1c >= 8% showed
      a drop of 1.1% in HbA1c 3 months after either class (p = 0.004). CONCLUSIONS: No
      significant difference in outcomes was found between the two diabetes education
      classes assessed. There was a trend towards improved glycemic control after both
      classes, and patients with high HbA1c levels demonstrated statistically
      significant improvements. This indicates that shorter sessions using didactic
      teaching methods may be equally effective in producing improvements in diabetes
      self-management as more intensive course formats.

PMID- 24674667
TI  - [Intracranial pressure monitoring in severe traumatic brain injury: A different
      perspective of the BestTrip trial].
AB  - The present study outlines a series of questions and reflections upon the recent
      publication of Chesnut et al., who compared 2 approaches to the treatment of
      intracranial hypertension (ICH) in severe head injuries: one with and the other
      without intracranial pressure monitoring (ICP). The authors concluded that no
      improved outcome was observed in the treatment group guided by ICP monitoring.
      The main concerns relate to the degree of training of the physicians involved in
      the monitoring and management of ICH in the ICP group, as well as to the possible
      inter-observer variability in interpreting the CT scans, the capacity of clinical
      signs to guide the treatment of ICH, and the suitability of randomization. The
      analysis of this trial should not be taken to suggest the futility of ICP
      monitoring but rather the need to correctly use the information afforded by ICP
      monitoring, with emphasis on the importance of the definition of alternative
      methods for non-invasive monitoring. 

PMID- 24674668
TI  - [Results of an in-hospital cardiac arrest training and response program].

PMID- 24674669
TI  - Mannosylated N-aryl substituted 3-hydroxypyridine-4-ones: synthesis,
      hemagglutination inhibitory properties, and molecular modeling.
AB  - Structural alterations of the aglycon portions of alpha-mannosides influence
      their inhibitory potency toward type 1-fimbriated Escherichia coli. The aim of
      our work was to prepare and explore inhibitory properties of novel mannosylated N
      aryl-substituted 3-hydroxypyridine-4-ones because they possess needed structural
      characteristics as possible FimH antagonists. Hemagglutination inhibitory tests
      showed that the examined 3-hydroxypyridine-4-one alpha-mannosides exhibited
      better inhibitory activity than methyl alpha-d-mannopyranoside used as a
      reference compound. Molecular modeling studies revealed the specific interactions
      responsible for the observed binding activities toward the mannose-specific FimH
      lectin. The activity depends on the substituent in p-position on the aglycon
      aromatic ring. 

PMID- 24674670
TI  - LIM homeodomain transcription factor Isl1 directs normal pyloric development by
      targeting Gata3.
AB  - BACKGROUND: Abnormalities in pyloric development or in contractile function of
      the pylorus cause reflux of duodenal contents into the stomach and increase the
      risk of gastric metaplasia and cancer. Abnormalities of the pyloric region are
      also linked to congenital defects such as the relatively common neonatal
      hypertrophic pyloric stenosis, and primary duodenogastric reflux. Therefore,
      understanding pyloric development is of great clinical relevance. Here, we
      investigated the role of the LIM homeodomain transcription factor Isl1 in pyloric
      development. RESULTS: Examination of Isl1 expression in developing mouse stomach
      by immunohistochemistry, whole mount in situ hybridization and real-time
      quantitative PCR demonstrated that Isl1 is highly expressed in developing mouse
      stomach, principally in the smooth muscle layer of the pylorus. Isl1 expression
      was also examined by immunofluorescence in human hypertrophic pyloric stenosis
      where the majority of smooth muscle cells were found to express Isl1. Isl1
      function in embryonic stomach development was investigated utilizing a tamoxifen
      inducible Isl1 knockout mouse model. Isl1 deficiency led to nearly complete
      absence of the pyloric outer longitudinal muscle layer at embryonic day 18.5,
      which is consistent with Gata3 null mouse phenotype. Chromatin
      immunoprecipitation, luciferase assays, and electrophoretic mobility shift assays
      revealed that Isl1 ensures normal pyloric development by directly targeting
      Gata3. CONCLUSIONS: This study demonstrates that the Isl1-Gata3 transcription
      regulatory axis is essential for normal pyloric development. These findings are
      highly clinically relevant and may help to better understand pathways leading to
      pyloric disease.

PMID- 24674671
TI  - Epithelioid sarcoma of the spine: case report and literature review.
AB  - Epithelioid sarcomas are rare mesenchymal neoplasms mainly arising in the limbs
      of young adults. We report the case of a 24-year-old male presenting low back
      pain radiating to both lower limbs, constipation and urinary retention. The MRI
      scan showed an intraspinal lesion extending from L4 to S2. Surgery resulted in
      gross total removal of the extradural lesion and partial removal of the
      intradural component. The immunohistological study of the lesion was consistent
      with an epithelioid sarcoma. The patient was submitted to radiotherapy and
      chemotherapy, but a local recurrence of the lesion and dissemination along the
      neuraxis were observed 3 months after surgery. Despite treatment, the patient
      died 4 months after the surgical procedure due to multiorgan failure. Despite
      there being isolated reports of epithelioid sarcomas appearing in the spine, this
      is, to our knowledge, the first case with intradural extension. 

PMID- 24674672
TI  - Cutaneous manifestations in patients with chronic renal failure on hemodialysis.
AB  - Patients with chronic renal failure (CRF) may exhibit various cutaneous
      abnormalities, including changes in skin colour, pruritus, xerosis, hair, nail
      and oral changes, metastatic calcinosis, and bullous dermatosis. These changes
      have a considerable negative effect on the patient's quality of life. Early
      recognition of cutaneous signs and prompt initiation of treatment can
      dramatically alter their course and decrease morbidity.

PMID- 24674673
TI  - Cytochrome P450 genetic polymorphism in neonatal drug metabolism: role and
      practical consequences towards a new drug culture in neonatology.
AB  - The cytochrome P450 superfamily (CYP450) in humans is formed by 57 functional
      monooxygenases critical for the metabolism of numerous endogenous and exogenous
      compounds. The superfamily is organized into 18 families and 44 subfamilies. CYP
      nomenclature is based on the identity of amino acids. The most important
      functions of the CYP450 are related to metabolism of endogenous compounds,
      detoxification of exogenous xenobiotics and decomposition of the vast majority of
      currently used drugs. The expression of CYP450 enzymes in the human body is
      characterized by a marked substrate and tissue specificity, the most important
      being localized in the liver, but also present in kidney, lung, brain, breast,
      prostate and in the small intestine. The human cytochrome P450 3A gene family
      (CYP3A) accounts for the largest portion of CYP450 proteins in human liver and
      includes 4 genes: CYP3A4, CYP3A5, CYP3A7, CYP3A43. Multiple and complex genetic
      variations, marked interindividual, interethnic and gender variability have been
      reported regarding CYP3A isoform expression and activity. Multiple factors may
      affect CYP3A expression and activity, such as inducers like rifampicin,
      phenobarbital, 3-methylcholantrene, beta-naphtoflavone, and dexamethasone. The
      maturation of organ systems, paralleled by ontogeny of drug-metabolizing enzymes
      during fetal life and in the first months of postnatal life, surely exerts
      profound effects on drug disposition, probably being the predominant factor
      accounting for age-associated changes in drug clearance. In fact, drug dosage in
      the perinatal period represents a continuous challenge for neonatologists. The
      purpose of this article is to provide a brief review of the pharmacokinetic
      differences between neonates and adults, showing the peculiarities of liver
      CYP450-related drug metabolism in the perinatal period and at birth, and to
      report the toxic mechanisms of liver injury in neonates, due to the most
      frequently utilized drugs in NICU centers. 

PMID- 24674674
TI  - Nerve growth factor interactions with mast cells.
AB  - Neuropeptides are involved in neurogenic inflammation where there is vasodilation
      and plasma protein extravasion in response to this stimulus. Nerve growth factor
      (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound
      which is important for survival of nociceptive neurons during their development.
      Therefore, NGF is an important neuropeptide which mediates the development and
      functions of the central and peripheral nervous system. It also exerts its
      proinflammatory action, not only on mast cells but also in B and T cells,
      neutrophils and eosinophils. Human mast cells can be activated by neuropeptides
      to release potent mediators of inflammation, and they are found throughout the
      body, especially near blood vessels, epithelial tissue and nerves. Mast cells
      generate and release NGF after degranulation and they are involved in
      iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a
      potent degranulation factor for mast cells in vitro and in vivo, promoting
      differentiation and maturation of these cells and their precursor, acting as a co
      factor with interleukin-3. In conclusion, these studies are focused on cross-talk
      between neuropeptide NGF and inflammatory mast cells. 

PMID- 24674675
TI  - Management of non-melanoma skin cancer in solid organ transplant recipients.
AB  - Non-melanoma skin cancer (NMSC) is the most frequent cancer observed in solid
      organ transplant recipients (SOTR). Early diagnosis, patient education, and
      modification of immunosuppression are effective measures for reduction of NMSC
      incidence. Many risk factors have been identified, including age at
      transplantation, fair skin, type of immunosuppressive drugs, cumulative sun
      exposure, viral infections, and various genetic markers. Skin self-examination
      and photoprotection should be encouraged in all transplanted patients. Long-term
      skin surveillance, early diagnosis and aggressive treatment of any suspicious
      lesion, reduction of immunosuppressive therapy, and conversion to mammalian
      target-of-rapamycin (m-TOR) inhibitors can be also effective measures for
      reduction of NMSC incidence. 

PMID- 24674677
TI  - ROCK activation in lung of idiopathic pulmonary fibrosis with oxidative stress.
AB  - The Rho-associated coiled-coil containing protein kinase, (Rho-kinase or ROCK)
      undergoes activation by oxidative stress. ROCK-II, which is an isoform of ROCK,
      is activated in a murine model of lung fibrosis. The present study evaluated the
      level of oxidative stress and activation of ROCK-II in patients with idiopathic
      pulmonary fibrosis (IPF). The ROCK-II level and the phosphorylation of myosin
      phosphatase subunit-1 (p-MYPT-1), a hallmark of ROCK activation, were examined by
      immunohistochemistry of lung tissue sections. The 8-iso prostaglandin-F2alpha (8
      isoPGF2alpha) level, as a marker of oxidative stress, of exhaled breath
      condensate was significantly higher in IPF patients than in control patients. In
      IPF lungs, ROCK-II was predominantly expressed by bronchial epithelial cells, as
      well as at a lower level by airway smooth muscle cells, vascular smooth muscle
      cells, and the fibroblasts of fibroblastic foci (FF). In addition, there was
      moderate p-MYPT-1 expression in these cells of IPF lungs. In control lungs, ROCK
      II was expressed by these cells. p-MYPT-1 was weakly expressed by the bronchial
      epithelial cells. In conclusion, ROCK-II was activated in various lung cells of
      IPF patients along with oxidative stress detected by 8-isoPGF2alpha elevation.
      The ROCK pathway may play a role in the development of IPF oxidative stress.

PMID- 24674676
TI  - Clinical efficacy, safety and anti-inflammatory activity of two sevelamer tablet
      forms in patients on low-flux hemodialysis.
AB  - Sevelamer hydrochloride is an ionic exchange resin with high affinity for
      phosphate. This phosphate-binding agent has few serious adverse reactions with
      the advantage of reducing total and low density lipoprotein (LDL) cholesterol
      levels. However, it is controversial as to whether sevelamer hydrochloride can
      modulate the inflammatory response via endotoxin reduction. Therefore, a single
      center, open-label, prospective and randomized study was performed to compare the
      clinical efficacy, safety and anti-inflammatory activity of two sevelamer
      hydrochloride tablet forms a branded tablet form, Renagel (Genzyme manufacturer)
      and its generic equivalent (EMS manufacturer). Twenty-eight chronic kidney
      disease volunteer patients at stage 5 (CDK 5D), on chronic low-flux hemodialysis
      carried out in 4-hour sessions, three times a week, were studied. The serum
      phosphorus, ionic calcium, total cholesterol and fractions, bicarbonate, blood
      pH, interleukin (IL)-6, IL-10, IL-1 beta and tumor necrosis factor-alpha (TNF
      alpha) levels were collected prior to dialysis at mid-week. The incidence of
      gastrointestinal adverse effects were determined at the end of the phosphate
      binder washout period as well as at the end of the fourth and eighth weeks of use
      of both tablet forms. The same magnitude of reduction in serum phosphorus was
      observed with both sevelamer tablet forms. Only the Renagel group showed lower
      total cholesterol and lower LDL cholesterol levels at the fourth and eighth week
      versus baseline. No significant differences in serum cytokine levels were
      identified in either drug group. However, the incidence of intestinal obstipation
      was higher among patients who used the generic equivalent form. In conclusion,
      Renagel and its EMS generic equivalent tablet forms have a similar clinical
      efficacy in reducing phosphorus in CKD 5D patients on low-flux hemodialysis and a
      similar safety profile.

PMID- 24674678
TI  - The significance of CA15-3 in breast cancer patients and its relationship to HER
      2 receptor status.
AB  - Breast cancer is estimated to be the most common malignancy affecting women in
      Iraq. The cancer antigen CA 15-3 has been used as a possible serum marker of
      occult and recurrent breast carcinoma, either alone or in combination with other
      tumor markers such as HER2/neu, that has evolved as a major classifier of
      invasive breast cancer and target of therapy for the disease. ELISA, used to
      evaluate serum levels of CA15-3 and immuno-histochemistry staining technique, was
      used to establish the HER2/neu status. The results of this study indicate an
      increased level of CA15-3 in breast cancer patients (29.02+/-1.79 IU/ml) as
      compared to both women with benign tumor and healthy controls (13.78+/-1.24 and
      8.92+/-0.48 IU/ml, respectively), and that this increase is associated to
      advanced stages. Patients with HER2/neu positive malignancies show elevated serum
      CA15-3 (37.09+/-2.55 IU/ml), as well as patients who developed recurrence
      (40.75+/-2.11 IU/ml). Our data study suggests that higher levels of CA 15-3 would
      be a reliable prognostic marker as they were directly related to advanced stages
      and recurrence. In addition persistent elevation of CA 15-3 was associated to
      HER2/neu positivity in breast cancer patients. 

PMID- 24674679
TI  - Suppression of CD4+ T lymphocyte activation in vitro and experimental
      encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75.
AB  - Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer
      therapy and are essential to immune responses, particularly through costimulation
      by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune
      intervention. PIK-75 is an efficient inhibitor of the PI3-K p110alpha catalytic
      subunits that suppresses tumor growth, and its effects on immune and autoimmune
      responses should be studied. Here, we describe the effect of PIK-75 on different
      immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in
      vitro (&#8805;0.1 &#956;M) inhibited T and B cell activation by Concanavalin A
      and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+
      T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was
      prevented by caspase inhibitors. At low nanomolar concentrations (&#8804;10 nM),
      PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-gamma
      production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts
      costimulated by ICOS, PIK-75 (less than 10 nM) inhibited IFN-gamma, IL-17A, or IL
      21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in
      ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG
      specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE,
      modulating lymphocyte function and survival. 

PMID- 24674680
TI  - Immunomodulatory and protective properties of tacrolimus in experimental scorpion
      envenomation.
AB  - Involvement of imbalance between pro- and anti-inflammatory events has been
      reported in the developed pathogenesis after scorpion envenomation. The
      immunosuppressive and anti-inflammatory properties of tacrolimus (FK-506) have
      been investigated: i) to better understand evolution of signaling pathways which
      are involved in the immune system ii) to reduce observed clinical signs while
      keeping a balance between pro- and anti-inflammatory cytokines. Naval Medical
      Research Institute (NMRI) mice received tacrolimus (1 mg/kg every 12 hours per
      os) for 21 days before envenomation with a sublethal dose (10 microg/20 g body
      weight) of Androctonus australis hector venom (Aah). Cell migration, pulmonary
      edema, exudation, Myeloperoxydase (MPO), Eosinophil peroxydase (EPO), C-reactive
      protein (CRP), C3, Creatine phosphokinase (CPK), aspartate aminotransferase
      (ASAT), alanine aminotransferase (ALAT), and hyperglycemia were analyzed 30 min,
      3 and 24 hours after injection of Aah venom. Histological analysis of lung
      parenchyma was undertaken 24 hours after envenomation. Aah lethality was
      evaluated on mice with or without pretreatment with tacrolimus. (Fab?)2 fragments
      (40 mg/kg) were also used as specific treatment in all protocols. Tacrolimus
      significantly inhibited cell migration, pulmonary edema, exudation, CRP and
      hyperglycemia. It also decreased MPO and EPO activities and prevented tissue
      damage in lung tissue, balancing seric parameter levels (CPK, ASAT and ALAT). The
      pretreated animals seemed to be protected by this macrolide against the venom
      lethality. These findings suggest that the overactivation of the immune system is
      one of the causes involved in the aggravation of the pathophysiological effects
      induced after envenomation. The obtained results showed that the use of F(ab?)2
      fragments as specific treatment cannot reduce the induced inflammatory response. 

PMID- 24674681
TI  - Vasoactive role for angiotensin II type 2 receptors in human radial artery.
AB  - Angotensin II type 2 receptors are believed to counter the effects of the
      angiotensin type 1 receptors and there is no data relating to the co-localisation
      of either receptor in human diseased arteries. We sought to determine whether
      AT2R counter the effects of AT1R and immunolocalise both receptors to cells in
      human diseased arteries. Human radial arteries (RA, n=11) were placed in organ
      bath chambers and preincubated with the AT2R antagonist PD123319 for twenty
      minutes before an angiotensin II dose response curve. Immunohistochemistry was
      performed to identify receptors and pathology was quantified by image analysis
      software. We observed both receptors in human arteries. Angiogenic blood vessels
      within occluded arteries expressed both receptors. PD123319 impaired angiotensin
      II mediated vasoconstriction by 20 percent (n=5, p less than 0.05), however in
      other arteries, PD123319 exacerbated angiotensin II-mediated vasoconstriction by
      60 percent (n=6, p less than 0.01), respectively. We conclude that inhibition of
      AT2R can enhance or reduce angiotensin II-mediated vasoconstriction. These data
      indicate that the role of AT2R in human diseased arteries is divergent although
      the AT2R-mediated vasorelaxation prevails. 

PMID- 24674682
TI  - Cytokine profiles and hepatic injury in occult hepatitis C versus chronic
      hepatitis C virus infection.
AB  - Occult hepatitis C virus (HCV) infection is a new entity that should be
      considered when diagnosing patients with abnormal liver functions of unknown
      origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2)
      cytokine profiles in patients with occult HCV infection versus chronic hepatitis
      C (CHC) infection, also to investigate any association between theses cytokines
      and liver histological features in both groups. Serum levels of Th1 cytokines (IL
      2, IFN-gamma) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult
      HCV infection compared to 50 patients with chronic hepatitis C infection and 30
      healthy controls. We have found that Th1 cytokines were significantly increased
      in patients with CHC infection than in both occult HCV infection and control
      groups (p less than 0.001). On the other hand, serum IL-4 levels were higher in
      occult HCV infection than in CHC and control groups (p less than 0.001).
      Furthermore, serum IL-10 levels were higher in both patient groups vs control
      group (pless than 0.001), with no significant difference between CHC and occult
      HCV groups. Finally, only serum IL-10 levels were significantly higher among
      patients with high activity (A2-A3) than those with low activity (A0-A1) in both
      CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult
      HCV infection exhibited a distinct immunoregulatory cytokine pattern that is
      shifted towards the Th2 arm. 

PMID- 24674683
TI  - Is osteopontin involved in cutaneous fibroblast activation? Its hypothetical role
      in scleroderma pathogenesis.
AB  - Osteopontin (OPN) is an extracellular matrix protein implicated in bone
      remodeling, but it presents also pro-inflammatory and pro-fibrotic properties.
      OPN expression also occurs upon exposure of cells to classical mediators of acute
      inflammation such as tumor necrosis growth factor alpha (TNF-alpha) and
      interleukin-1 beta (IL-1beta), as well as fibrogenic cytokines such as
      transforming growth factor beta (TGF-beta), although a detailed understanding of
      these regulatory pathways is still unknown. Plasma OPN levels in both limited and
      diffuse systemic sclerosis patients (lSSc and dSSc) were statistically higher
      compared to those of control subjects. Immunohistology demonstrated that high TGF
      beta levels, alpha smooth muscle actin (alphaSMA) levels and consequently high
      OPN levels were found in the affected skin of sclerodermic patients (lSSc and
      dSSc) compared to levels found in healthy skin. In order to better understand how
      OPN interferes with the fibrotic process, healthy skin fibroblasts were treated
      for 24 and 48 hours with bleomycin and with endothelin-1 (ET-1) plus TGF-beta in
      order to induce the fibrogenesis. After 48 hours of stimulation, healthy treated
      fibroblasts showed statistically increased alphaSMA levels (index of
      differentiation into myofibroblasts) and simultaneously statistically increased
      OPN levels compared to healthy untreated ones. This study demonstrates that OPN
      levels increase simultaneously with the increasing of alphaSMA levels, therefore
      it is reasonable to hypothesize that OPN interferes in the pathogenesis of
      Systemic Sclerosis in the early stage of fibroblast differentiation process. 

PMID- 24674684
TI  - Multiple cytokine-producing testicular malignant lymphoma with clinical symptoms
      resembling infectious signs.
AB  - We present the case of a 64-year-old male with painful swelling of the bilateral
      testes and epididymides, high fever, leukocytosis, and an elevated C-reactive
      protein (CRP) level. This is the first case report of testicular diffuse large B
      cell lymphoma, not otherwise specified (DLBCL, NOS) immunostained for multiple
      cytokines and their receptors, which clearly demonstrates that tumor cells
      express multiple cytokines [interleukin-6 (IL-6) and granulocyte colony
      stimulating factor (G-CSF)] and their receptors [IL-6 receptor (IL-6R) and G-CSF
      receptor (G-CSFR)]. The clinical course showed that the reduction in tumor size
      was accompanied by a corresponding improvement in clinical symptoms and
      peripheral blood findings. Such clinical investigation may lead clinicians to
      misdiagnose inflammatory disease rather than neoplastic disease. Recognizing this
      paraneoplastic phenomenon associated with some cases of testicular DLBCL, NOS is
      important. In addition, this case suggests that the growth of tumor cells may be
      promoted through autocrine mechanisms of IL-6 and G-CSF, which are produced by
      tumor cells. The possibility that these cytokines can be produced by tumor cells
      and can accelerate tumor proliferation should be considered to be a cause of
      severe clinical symptoms, an aggressive clinical course, and an indication of the
      necessity of treatment. Certain cytokines may be used as tumor markers in some
      cases of DLBCL, NOS. 

PMID- 24674685
TI  - Treatment with a combination of omalizumab and specific immunotherapy for severe
      anaphylaxis after a wasp sting.
AB  - Hymenoptera venom anaphylaxis after bee or wasp sting is a common problem that
      affects about 1.2 percent to 3.5 percent of the general population. Venom
      specific immunotherapy (VIT) is an established mode of treatment for
      immunoglobulin (Ig) E-mediated Hymenoptera venom allergy. However, VIT may often
      be associated with immediate anaphylaxis which can lead to treatment withdrawal.
      Several cases published in recent years suggest that omalizumab, used as add-on
      therapy may be able to prevent anaphylaxis during VIT. We report the case of a 30
      year-old woman, suffering from mild persistent asthma, who had a history of
      severe anaphylactic reactions after yellow jacket sting, and after eating
      peanuts, contact with guinea pig hair, and i.v. administration of dexamethasone
      natrium phosphate. Initial specific immunotherapy had to be stopped due to severe
      anaphylaxis (hypotension, dyspnea, and angioedema). The immunotherapy was
      reintroduced accompanied by the anti-immunoglobulin (Ig) E monoclonal antibody
      omalizumab. Subcutaneous omalizumab 150 mg was initiated 4 weeks after the
      anaphylaxis incident and 1 day before the resumption of VIT. Rush treatment was
      uneventful, and the usual cumulative dose of 111.1 microg was successfully
      reached. The combination of omalizumab and VIT is a valid option of therapy for
      these patients and could reduce asthma and food allergy symptoms.

PMID- 24674686
TI  - Management of immunosuppression and antiviral treatment before and after heart
      transplant for HIV-associated dilated cardiomyopathy.
AB  - Infection with HIV may lead to the development of cardiomyopathy as improved
      antiretroviral regimens continue to prolong patient life. However, advanced
      therapeutic options, such as heart transplant, have until recently been precluded
      to HIV-positive persons. A favorable long-term outcome has been obtained after
      kidney or liver transplant in HIV-positive recipients fulfilling strict
      virological and clinical criteria. We recently reported the first heart
      transplant in a HIV-infected patient carried out in our center. In this article,
      we detail the major challenges we faced with the management of antiretroviral and
      immunosuppressive treatments over the first 3 years post-transplant. The patient
      had developed dilated cardiomyopathy while on antiretroviral treatment with
      zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and
      had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac
      resynchronization therapy and maximal drug therapy, the patient progressed to end
      stage heart failure, requiring heart transplant. He was placed on a standard
      immune suppressive protocol including cyclosporine A and everolimus. Despite its
      potential pharmacokinetic interaction with efavirenz, everolimus was chosen to
      reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs
      were monitored and remained within the target range, although high doses of
      everolimus were needed. There were no infectious, neoplastic or metabolic
      complications during a 3-year follow-up. In summary, our experience supports
      previous data showing that cardiac transplantation should not be denied to
      carefully selected HIV patients. Careful management of drug interactions and
      adverse events is mandatory. 

PMID- 24674687
TI  - Azithromycin anaphylaxis in children.
AB  - Allergic reactions associated to the use of macrolides are uncommon; in
      particular only two cases of anaphylaxis with erithromycin and clarithromycin
      have been reported to date. The aim of this study was to investigate macrolide
      induced anaphylaxis. Between December 2007 and December 2011, 136 consecutive
      children were referred to the Allergy Unit of A. Meyer Children's Hospital
      because of a past history of reactions to macrolides. Allergy work-ups were
      carried out according to the European Network for Drug Allergy protocol.
      Anaphylaxis was diagnosed according to the clinical criteria proposed by Sampson
      et al. and graded according to Brown SGA et al. Sixty-six out of 136 patients
      completed the allergologic work-up and among them we investigated three cases of
      anaphylaxis due to azithromycin which included one child with anaphylaxis to both
      clarithromycin and azithromycin. In two of the children with anaphylaxis, the
      diagnosis was only confirmed with the skin prick test, the third was positive to
      the Intradermal Test. The azithromycin allergy shows a surprisingly high
      sensitivity to the in-vivo tests. Moreover, this study shows that cross
      reactivity may occur between different macrolidic molecules; it has even been
      suggested that macrolide allergies are unlikely to be class allergies.

PMID- 24674688
TI  - Pompholyx of the hands after intravenous immunoglobulin therapy for clinically
      isolated syndrome: a paediatric case.
AB  - Pompholyx is a common eruption of small vesicles on the palms, soles, and/or
      lateral aspects of the fingers. It has a multifactorial etiology, including
      genetic determinants, allergy to metals, and id reaction; rarely it is a drug
      related side effect. We report a paediatric case of pompholyx of the hands
      related to the intravenous immunoglobulin (IVIG) therapy for Clinically Isolated
      Syndrome (CIS). A 10-year-old boy, received an IVIG therapy (Venital, Kedrion
      Spa, Italy) at a dose of 400 mg/kg daily for five days. The fifth day of IVIG
      infusion, a symmetrical vesicular eruption appeared on the palms of the hands and
      on lateral aspects of the fingers. The lesions improved with application of
      topical steroids in few days. The mechanism of induction of pompholyx by IVIG
      therapy is unknown. A review of the Literature suggests the hypothesis that
      dyshidrotic eczematous reactions may be related not only to the type of IVIG, to
      the dose and the rates of infusion, but also to an allergic response to
      excipients and preservatives contained in the drug, probably elicited by an
      underlying neurological disease in some cases. 

PMID- 24674689
TI  - Systemic nickel allergy syndrome: epidemiological data from four Italian allergy
      units.
AB  - The prevalence of nickel hyper-sensitivity varies widely in different countries,
      nevertheless it is the leading cause of contact dermatitis. The presence of
      nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can
      provoke/aggravate eczema and systemic contact dermatitis as well as cause extra
      cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms,
      correlated to the ingestion of nickel-containing foods and beverages, in nickel
      patch test positive individuals, defines the so called Systemic Nickel Allergy
      Syndrome (SNAS), a condition successfully treated by oral desensitization.
      Although numerous studies have investigated the prevalence of contact nickel
      allergy or addressed the relationship between nickel intake and onset of systemic
      symptoms, to our knowledge no epidemiological studies have attempted to estimate
      the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients
      (1,696), afferent to four allergy units in Sicily, a region of southern Italy,
      from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent)
      of the 1,696 studied, suggesting that this clinical entity may be an emergent
      allergological condition rather than an occasional finding. The most common
      symptoms complained of in our population were cutaneous (51 patients),
      gastrointestinal (87 patients) and other systemic clinical manifestations (37
      patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented
      IgE-mediated food allergy with a statistically significant association
      (X2=16.950; P<0.0001), therefore suggesting underlying cross-facilitating
      pathways. These findings need confirmation on wider populations but may help
      allergists to suspect, during common clinical practice, that cutaneous and extra
      cutaneous symptoms may be referred to nickel intake and deserve specific in-depth
      investigation. 

PMID- 24674690
TI  - The growth of Streptococcus mutans in different milks for infant feeding.
AB  - After birth various bacterial species, mainly streptococci, colonize the oral
      cavity and are frequently isolated from carious lesions in children. Previous
      studies suggest that an earlier colonization of a child's mouth by cariogenic
      organisms might be related to a higher risk of caries. The aim of this study is
      to assess the influence of different milks for infant feeding on the growth of
      Streptococcus mutans (SM) colonies. Three human milk samples from three different
      mothers and five infant formulas were tested. To prepare the bacterial inoculum,
      SM was grown in Brain Heart Infusion broth for 18 hours at 37 degrees C in
      microaerophilic atmosphere. The growth of SM was determined immediately after the
      inoculation of milks (T0) and after 24 hours (T24) of incubation. After 24 hours
      of incubation (DeltaT= CFUs/ml at T24 ? CFUs/ml at T0) the bacterial growth
      changes were different among milks. Among the complementary milks tested, DeltaT
      of formulas supplemented with Lactobacillus reuteri and with Bifidobacterium
      lactis was lower than those of non-supplemented formula. In conclusion, on the
      basis of the reduced SM growth in milks supplemented with probiotics, we may
      speculate that these formulas have a preventive effect on the development of
      caries in children.

PMID- 24674691
TI  - Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of
      Clostridium difficile colitis with a probioticum.
AB  - The yeast Saccharomyces boulardii is a biotherapeutic agent used for the
      prevention and treatment of several gastrointestinal diseases, such as diarrhoea
      caused by Clostridium difficile, in addition to the antibiotic therapy. In this
      study we report a case of Saccharomyces cerevisiae fungemia in a patient with
      Clostridium difficile-associated diarrhoea (CDAD) treated orally with S.
      boulardii in association with vancomycin. The identification of the S. cerevisiae
      was confirmed by molecular technique. Fungemia is a rare, but a serious
      complication to treatment with probiotics. We believe it is important to remind
      the clinicians of this risk when prescribing probiotics, especially to
      immunocompromised patients. 

PMID- 24674693
TI  - Borophosphates and silicophosphates as plausible contributors to the emergence of
      life.
AB  - Scientific explanations for the origin of life are incomplete and may differ on
      some issues. Here, we argue that some prebiological steps have occurred in
      environments with borophosphates and/or silicophosphates in the form of
      hydrogels, on the basis of their chemical groups and structural properties. These
      could have decreased the diffusion rate of some prebiotic molecules, stabilized
      molecules with vicinal cis-diol groups, reduced the hydrolytic activity of water
      and inserted catalytic metal ions into their networks. Additionally, these
      hydrogels could have acted as reaction media, supplied a phosphate source for
      phosphorylations and produced crystals that may have permitted enantiomeric
      enrichment of prebiotic molecules, thus providing conditions for the emergence of
      protocells. 

PMID- 24674692
TI  - Systemic neutralization of IL-17A significantly reduces breast cancer associated
      metastasis in arthritic mice by reducing CXCL12/SDF-1 expression in the
      metastatic niches.
AB  - BACKGROUND: IL-17A is a pro-inflammatory cytokine that is normally associated
      with autoimmune arthritis and other pro-inflammatory conditions. Recently, IL-17A
      has emerged as a critical factor in enhancing breast cancer (BC)-associated
      metastases. We generated immune competent arthritic mouse models that develop
      spontaneous BC-associated bone and lung metastasis. Using these models, we have
      previously shown that neutralization of IL-17A resulted in significant reduction
      in metastasis. However, the underlying mechanism/s remains unknown. METHODS: We
      have utilized two previously published mouse models for this study: 1) the pro
      arthritic mouse model (designated SKG) injected with metastatic BC cell line
      (4T1) in the mammary fat pad, and 2) the PyV MT mice that develop spontaneous
      mammary gland tumors injected with type II collagen to induce autoimmune
      arthritis. Mice were treated with anti-IL-17A neutralizing antibody and monitored
      for metastasis and assessed for pro-inflammatory cytokines and chemokines
      associated with BC-associated metastasis. RESULTS: We first corroborate our
      previous finding that in vivo neutralization of IL-17A significantly reduced
      metastasis to the bones and lungs in both models. Next, we report that treatment
      with anti-IL17A antibody significantly reduced the expression of a key chemokine,
      CXCL12 (also known as stromal derived factor-1 (SDF - 1)) in the bones and lungs
      of treated mice. CXCL12 is a ligand for CXCR4 (expressed on BC cells) and their
      interaction is known to be critical for metastasis. Interestingly, levels of
      CXCR4 in the tumor remained unchanged with treatment. Consequently, protein
      lysates derived from the bones and lungs of treated mice were significantly less
      chemotactic for the BC cells than lysates from untreated mice; and addition of
      exogenous SDF-1 to the lysates from treated mice completely restored BC cell
      migration. In addition, cytokines such as IL-6 and M-CSF were significantly
      reduced in the lung and bone lysates following treatment. The data presented
      suggests that systemic neutralization of IL-17A can block the CXCR4/SDF-1
      signaling pathway by reducing the expression of SDF-1 in the metastatic niches
      and significantly reducing metastasis in both mouse models. CONCLUSION: In our
      model, neutralization of IL-17A regulates SDF-1 expression in the metastatic
      niches either directly or indirectly via reducing levels of IL-6 and M-CSF.

PMID- 24674694
TI  - Prevalence of halitosis in children considering oral hygiene, gender and age.
AB  - BACKGROUND: To date, few studies have addressed halitosis in the paediatric
      population. As such, the aim of the present study was to investigate symptoms,
      signs and risk factors associated with halitosis in healthy children and to
      present a model based on the clinical data that predicts the presence of
      halitosis. METHODS: A total of 101 individuals were included. All patients
      received a questionnaire that queried on sociodemographic characteristics, self
      reported halitosis and dental treatment history. Individuals received a thorough
      intra-oral examination, and the volatile sulphur compounds (VSC) were measured to
      test the presence of halitosis with a portable sulphide monitor (Halimeter((r));
      Interscan Co., Chatsworth, CA, USA). The distribution of the sociodemographic
      characteristics, self-reported halitosis, dental treatment history and other oral
      features was evaluated. Finally, a statistical model was constructed with the
      best set of features to predict halitosis in children. RESULTS: The median age
      was 12.0 years (mean: 11.7 +/- SD 2.7) with 54.5% males. Halitosis (VSC > 100
      parts per billion, or ppb) was objectively measured in 37.6% of patients. For
      comparison purposes, Bayesian network was obtained using clinical and demographic
      data. The model consisted of four variables (sex, age, oral hygiene status and
      self-reported halitosis) directly related to the presence of halitosis (VSC > 100
      ppb). This model achieved 76.4% area under receiver operating characteristics
      curve (AUROC). Overall, female patients or individuals with dental plaque on more
      than 25% of the dental surfaces or patients older than 13 year old were more
      prone to present with halitosis. CONCLUSIONS: The results suggest that halitosis
      in the paediatric population is related to poor oral hygiene and may be more
      common in females and older individuals. This specific predictive model may be
      useful to identify subgroups to target for intervention to treat oral halitosis.

PMID- 24674695
TI  - Diabetes management unawareness: what do bedside nurses know?
AB  - BACKGROUND: Nurses are responsible for critical aspects of diabetes care.
      PURPOSE: The purpose of this study was to examine nurses' knowledge of inpatient
      diabetes management principles before and after a structured diabetes education
      program. METHODS: In this descriptive, correlation study, 2250 registered nurses
      working in a quaternary health care center completed a 20 question assessment.
      The assessment was administered pre and post attendance at a 4hour diabetes
      management course. FINDINGS: Nurses' knowledge of inpatient diabetes management
      principles was low. There was no correlation between knowledge scores and age,
      education, employment status, years of experience or clinical specialty.
      CONCLUSIONS: In general, our findings suggest that nurses do not feel comfortable
      and are not adequately prepared to make patient care decisions or provide
      survival skill education for patients with diabetes in the hospital.

PMID- 24674696
TI  - Hand injuries due to firework devices: a series of 58 cases.
AB  - Fireworks or firecrackers can cause serious accidents. They are classified from
      K1 to K4 according to the amount of powder they contain. In Alsace (France), a
      type-K1 firecracker is available on the free market and the K2 and K3 ones are
      prohibited. The aim of this study was to reveal the effects of measures taken in
      order to prevent repercussions related to hand injuries caused by fireworks.
      Patients who fell victim to firework incidents have been recorded since 2006,
      starting date of the prevention campaign. Records have been taken on the
      circumstances, the group of firecracker, the level of injury and the severity of
      the injury in four stages. Our series included 62 hands from 58 patients (average
      age: 25 years), including two women. Most of them sustained their injury during
      the night of New Year's Eve. The study dealt with 21 K1, and 35 K2 or K3. We
      registered 29 cases of grade I, 2 grades II, 21 grades III and 9 grades IV. One
      patient died. The numbers of consultations, K2/K3 injuries and number of
      surgeries increased from 2006 to 2012. Our results show that firework-related
      injuries to the hand are serious, pluridigital, multistage and/or bilateral.
      Prevention was ineffective but should be improved and strengthened, as a total
      ban on fireworks is a counterproductive measure. 

PMID- 24674697
TI  - [Collagenase injection in Dupuytren's disease, evaluation of the ultrasound
      assisted technique].
AB  - Since October 2011, the enzymatic lysis of Dupuytren's cord was introduced in
      Switzerland (Xiapex((r)), Auxilium Pharmaceuticals, Pfizer). Here we present our
      first university experience and underline the major role of ultrasound during the
      injection. Between December 2011 and February 2013, 52 injections were performed
      to eliminate 43 Dupuytren's cords in 33 patients. The mean age of the patients
      was 64.4 +/- 8.5 years. Complications were documented for each patient. Before,
      directly after and after a minimum of 6 months post-injection, the contracture of
      the treated joint was measured with use of a goniometer. The DASH score was
      evaluated after a minimum of 6 months and the patients were asked to subjectively
      evaluate the outcome of the treatment (very good, good, mild, poor) and whether
      they would reiterate it if necessary. Four skin defects, one lymphangitis, and
      one CRPS were responsible for a complication rate of 18%. There was no infection
      and no tendon rupture in the series. The mean MCP joint contracture was
      respectively 36.8 +/- 27.4 degrees , 3.5 +/- 7.8 degrees  (gain of mobility
      compared to the preoperative situation 33.3 degrees , P<0.001), and 8.4 +/- 13.9
      degrees  (gain 28.4 degrees , P<0.001) respectively before, just after and at the
      long-term clinical control. The mean PIP joint contracture was respectively 36.5
      +/- 29.1 degrees , 5.9 +/- 6.7 degrees  (gain 30.6 degrees , P<0.001), and 15.1
      +/- 13.8 degrees  (gain 21.4 degrees , P<0.001) respectively before injection,
      just after and at the long-term clinical control. The DASH score decreased from
      24 +/- 14 to 7 +/- 9 (P<0.001). Eighty-one per cent of the patients were
      satisfied or very satisfied of the treatment. All but two would reiterate the
      treatment if necessary. Ultrasound is able to target the injection of collagenase
      in order to reduce complications. The short-term results of this non-invasive
      therapy are very promising however comparison with conventional procedures is
      difficult as the long-term results are lacking.

PMID- 24674698
TI  - Prognostic factors and survival in primary adult high grade brainstem
      astrocytoma: a population based study from 1973-2008.
AB  - Adult brainstem astrocytomas are a rare and heterogeneous group of malignancies.
      Most reports represent low-grade gliomas. This study used the Surveillance,
      Epidemiology and End Results (SEER) database to analyze the association between
      survival and demographic factors, tumor histology, and treatment characteristics
      among adult patients with high-grade brainstem astrocytoma (HGBSA). Adult
      patients with histologically confirmed diagnoses of primary HGBSA were studied.
      In univariate and multivariate analysis, we investigated the effect of
      demographics, tumor histology and treatment modality on survival. Overall median
      survival in the cohort of 240 adult patients was 7months, with 1, 2, 5 and 10year
      survival rates of 33.2%, 19.7%, 10.1%, and 8.3%, respectively. Age >50years
      (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.45-2.70, p<0.001) and
      grade IV versus grade III tumor (HR 1.61, 95% CI 1.15-2.26, p=0.006) were
      associated with statistically significant increased mortality in multivariate
      analyses. Surgical intervention trended toward association with lower mortality
      (HR 0.68, 95% CI 0.47-1.01, p=0.055). Our findings suggest that in patients with
      HGBSA, younger age and lower-grade histology are associated with better
      prognosis. Surgical intervention trended towards a significant association with
      better outcome, while radiation treatment was not associated with a statistically
      significant benefit in survival. 

PMID- 24674699
TI  - Panophthalmoplegia and vision loss after cosmetic nasal dorsum injection.

PMID- 24674700
TI  - Unilateral multilevel interlaminar fenestration: a minimally invasive approach
      for cervical intramedullary lesions.
AB  - The traditional approach for cervical intramedullary lesions is laminectomy, but
      the procedure may result in spinal instability and spinal deformity. Unilateral
      multilevel interlaminar fenestration (UMIF) is an alternative minimally invasive
      approach that may have great advantages in preserving spinal stability. However
      its use in cervical intramedullary lesions is rare, and the indications, safety
      and limitations of this approach for cervical intramedullary lesions are still
      under investigation. We report five patients (three males, two females, age range
      12-46 years) who were treated between 2010 and 2011 for cervical intramedullary
      lesions. The lesions included three ependymomas, one astrocytoma and one
      ependymal cyst, and the locations of the lesions were at the medulla-T2, C4-T1,
      C5-C7, C4-C7 and C6-C7. All of these lesions were completely removed through
      UMIF, and all patients had stable or improved neurological status after surgery.
      No recurrences or spinal deformities were detected during the follow-up period
      which ranged from 24 to 35 months (mean=27.4 months). UMIF is a feasible approach
      for selected cervical intramedullary lesions. This approach allows complete
      resection of multilevel lesions without increasing the risk of injury to the
      spinal cord, and minimizing the risk of postoperative spinal instability. The
      indications for and limitations of UMIF are discussed.

PMID- 24674701
TI  - Formulations: friendly, fast, forgiving and flexible.

PMID- 24674702
TI  - Atrial fibrillation .... more than simply being irregularly irregular.

PMID- 24674703
TI  - Continuous infusions of midazolam and interrupted hydration - such as insulin
      infusions without glucose?
AB  - The Liverpool Care Pathway (LCP) for the dying patient is a UK care pathway
      covering palliative care options for patients in the final days or hours of life;
      it has recently been recommended for decommission in the UK following an
      independent review. The pathway was widely implemented in UK hospitals in part
      because of governmental financial incentives. One of the criticisms of the LCP
      included reports of the rapid escalation to continuous infusions of sedatives in
      patients who then became quickly unconscious and unable to communicate. 

PMID- 24674704
TI  - Prison prescribing practice: practitioners' perspectives on why prison is
      different.
AB  - The current prison population in England and Wales has multiple, complex
      healthcare needs, presenting unique challenges to those caring for prisoners.
      Prison numbers have increased dramatically in the last 10 years. There are now
      approximately 84,000 prisoners in England and Wales and 120,000 new episodes of
      imprisonment each year . The authors all contribute to prison healthcare. Below,
      we discuss a key issue arising from first-hand experience of prisoners' health
      and social care needs, the prescription of psycho-active drugs by primary and
      secondary care practitioners. This is a core medical task, but beset with
      difficulties. These difficulties are not necessarily encountered in other areas
      of prison healthcare. However, they do illustrate how providing healthcare to
      prisoners is complex, often lacking a research base and can have pitfalls that
      are not obvious to the outsider.

PMID- 24674705
TI  - The added diagnostic value of procalcitonin in elderly patients.

PMID- 24674706
TI  - Extracorporal life support (ECLS) in acute ischaemic cardiogenic shock.

PMID- 24674707
TI  - Equity impact of population-level interventions and policies to reduce smoking in
      adults: a systematic review.
AB  - BACKGROUND AND AIMS: There is strong evidence about which tobacco control
      policies reduce smoking. However, their equity impact is uncertain. The aim was
      to assess the effectiveness of population-level interventions/policies to reduce
      socioeconomic inequalities in adult smoking. METHODS: Systematic review of
      studies of population-level interventions/policies reporting smoking-related
      outcomes in adults of lower compared to higher socioeconomic status (SES).
      References were screened and independently checked. Studies were quality
      assessed. Results are presented in a narrative synthesis. Equity impact was
      assessed as: positive (reduced inequality), neutral (no difference by SES),
      negative (increased inequality), mixed (equity impact varied) or unclear.
      RESULTS: 117 studies of 130 interventions/policies were included: smokefree (44);
      price/tax (27); mass media campaigns (30); advertising controls (9); cessation
      support (9); settings-based interventions (7); multiple policies (4). The
      distribution of equity effects was: 33 positive, 36 neutral, 38 negative, 6
      mixed, 17 unclear. Most neutral equity studies benefited all SES groups. Fourteen
      price/tax studies were equity positive. Voluntary, regional and partial smokefree
      policies were more likely to be equity negative than national, comprehensive
      smokefree policies. Mass media campaigns had inconsistent equity effects.
      Cigarette marketing controls were equity positive or neutral. Targeted national
      smoking cessation services can be equity positive by achieving higher reach among
      low SES, compensating for lower quit rates. CONCLUSIONS: Few studies have
      assessed the equity impact of tobacco control policy/interventions. Price/tax
      increases had the most consistent positive equity impact. More research is needed
      to strengthen the evidence-base for reducing smoking inequalities and to develop
      effective equity-orientated tobacco control strategies.

PMID- 24674708
TI  - Frontal alpha EEG asymmetry before and after behavioral activation treatment for
      depression.
AB  - BACKGROUND: Mid-frontal and mid-lateral (F3/F4 and F7/F8) EEG asymmetry has been
      associated with motivation and affect. We examined alpha EEG asymmetry in
      depressed and healthy participants before and after Behavioral Activation
      treatment for depression; examined the association between alpha EEG asymmetry
      and motivational systems and affect; and evaluated the utility of alpha EEG
      asymmetry in predicting remission. METHODS: Depressed (n=37) and healthy
      participants (n=35) were assessed before and after treatment using a clinical
      interview, a task to measure baseline EEG, and questionnaires of behavioral
      activation and inhibition, avoidance, and affect. RESULTS: Alpha EEG asymmetry
      was significantly higher in depressed than healthy participants at pre-treatment,
      positively correlated with negative affect and behavioral inhibition, and
      inversely correlated with lower behavioral activation sensitivity. CONCLUSIONS:
      Heightened alpha EEG asymmetry in depressed participants was significantly
      associated with increased behavioral inhibition and negative emotion and was
      independent of clinical remission.

PMID- 24674709
TI  - Comparison of two approaches of intestinal absorption by puerarin.
AB  - INTRODUCTION: Everted gut sac (EGS) and in situ single-pass intestinal perfusion
      (SPIP) have been widely used in the study of drug absorption and
      biopharmaceutical classification systems (BCS). Furthermore, they could also be
      applied in the research of drug intestinal first-pass metabolism. Since most of
      Chinese herbal medicines (CHMs) are orally administrated, it is necessary to
      study the permeability of active ingredients of CHMs. Thus, we attempted to apply
      the EGS and SPIP models to study the permeability of puerarin, one of the active
      marker compounds (AMCs) of Puerariae Radix. METHODS: In the present study, three
      rat models of ex vivo and in situ, EGS, SPIP, and in situ intestinal perfusion
      with venous sampling (IPVS), were established to determine the permeability
      coefficient of puerarin. The apparent permeability coefficient (Papp) was
      obtained by EGS. The SPIP model was used to determine the effective permeability
      coefficient (Peff) in different intestinal segments. The blood permeability
      coefficient (Pblood) was determined by IPVS. Puerarin concentration of perfusion
      and blood samples were measured by HPLC. RESULTS: Puerarin could filter into EGS
      incubated in aqueous extract of Puerariae Radix or puerarin solution. In the SPIP
      experiment, the concentration effect on Peff was observed in the ileum, but not
      in the other three intestinal segments. The Pblood was 0.068+/-0.002*10(-5)cm/s
      and was 16-fold lower than the Peff (1.114+/-0.153*10(-5)cm/s) in the IPVS
      experiment at 80MUg/mL puerarin. As expected, the Peff (1.24+/-0.11*10(-5)cm/s)
      in SPIP did not differ from the Peff in IPVS. The Papp was 0.199*10(-5)cm/s at
      1200MUg/mL puerarin, 10-fold lower than Peff (2.047+/-0.116*10(-5)cm/s) in SPIP.
      DISCUSSION: Three models for permeability were successfully practiced in the
      study of puerarin absorption and our research strategy will be useful for herbal
      constituent absorption in the future.

PMID- 24674710
TI  - [Prevalence and epidemiology of Barrett's esophagus in the province of
      Barcelona].
AB  - INTRODUCTION: The prevalence of Barrett's esophagus (BE) varies from 0.45% to
      2.2% in patients who undergo upper endoscopy and is >12% when the indication is
      for reflux symptoms. The prevalence has progressively increased in recent years
      but is unknown in the population of the province of Barcelona. OBJECTIVES: To
      determine the prevalence of BE and its epidemiological characteristics in our
      population. PATIENTS AND METHODS: We prospectively evaluated patients referred to
      the Endoscopy Unit of Hospital Clinic and Hospital General de Catalunya for an
      upper endoscopy. We excluded patients with known BE, prior upper endoscopy,
      esophagogastric surgery or refusal to participate in the study. Demographic data,
      alcohol intake, Helicobacter pylori infection and consumption of antisecretory
      agents were recorded, among other information. Participants completed a
      standardized questionnaire to assess the presence of gastroesophageal reflux
      disease (GERD) symptoms and their severity. RESULTS: Between July 2010 and July
      2012, we included 200 patients (100 in each center). The mean age was 48.9 +/-
      15.6 years and the majority were women (n=120, 60%). Symptoms of GERD were
      present in 46 patients (23%) and some degree of esophagitis was present in 31
      (15.5%). Infection by H. pylori was present in 29.7%. BE was found endoscopically
      in 14 (7%) patients, but was histologically confirmed in only 8 (4%). The only
      variable that correlated with the finding of BE was male sex. CONCLUSION: The
      prevalence of BE in our environment is similar to that reported in Western
      countries. The absence of reflux symptoms does not rule out the possibility of
      BE.

PMID- 24674712
TI  - Obesity and the risk of stillbirth: a population-based cohort study.
AB  - OBJECTIVE: Obesity is a known risk factor for stillbirth. However, this
      relationship has not been characterized fully. We attempted to further examine
      this relationship with a focus on delivery near and at term. STUDY DESIGN: We
      designed a retrospective cohort study of singleton nonanomalous live births and
      stillbirths in the states of Washington and Texas to examine the associations of
      maternal prepregnancy body mass index (BMI) and risk of stillbirth. Confounder
      adjusted hazard ratio of stillbirth in relation to BMI was estimated through Cox
      proportional hazards regression model. The hazard ratio was used to estimate the
      population-attributable risk. We also estimated the fetuses who were at risk for
      stillbirth based on gestational age. RESULTS: Among 2,868,482 singleton births,
      the overall stillbirth risk was 3.1 per 1000 births (n = 9030). Compared with
      normal-weight women, the hazard ratio for stillbirth was 1.36 for overweight
      women, 1.71 for class I obese women, 2.00 for class II obese women, 2.48 for
      class III obese women, and 3.16 for women with a BMI of >=50 kg/m(2). The fetuses
      who are at risk for stillbirth increased after 39 weeks' gestation for each
      obesity class; however, the risk increased more rapidly with increasing BMI.
      Women with a BMI of >=50 kg/m(2) were at 5.7 times greater risk than normal
      weight women at 39 weeks' gestation and 13.6 times greater at 41 weeks'
      gestation. Obesity was associated with nearly 25% of stillbirth that occurred
      between 37 and 42 weeks' gestation. CONCLUSION: There is a pronounced increase in
      the risk of stillbirth with increasing BMI; the association is strongest at early
      and late-term gestation periods. Extreme maternal obesity is a significant risk
      factor for stillbirth.

PMID- 24674711
TI  - Optimisation of an immunohistochemistry method for the determination of androgen
      receptor expression levels in circulating tumour cells.
AB  - BACKGROUND: AZD3514 inhibits and down regulates the androgen receptor (AR) and
      has undergone clinical trials in prostate cancer. To provide proof-of-mechanism
      (POM) in patients, an immunohistochemistry (IHC) method for determination of AR
      in circulating tumour cells (CTC) was developed and validated. METHODS: After an
      assessment of specificity validation focused on intra- and inter-operator
      reproducibility utilising a novel modification of incurred sample reanalysis
      (ISR). beta-Content gamma-confidence tolerance intervals (BCTI) and Cohen's Kappa
      (kappa) were employed in statistical analysis of results. RESULTS: In a first set
      of IHC reproducibility experiments, almost perfect agreement was recorded
      (kappa=0.94) when two different operators scored CTC as overall positive or
      negative for AR. However, BCTI analysis identified a specific bias in scoring
      staining intensity, where one operator favoured moderate over strong assignments,
      whereas the reverse was the case with the second operator. After a period of
      additional training involving deployment of a panel of standardised images, a
      second set of validation experiments were conducted. These showed correction of
      the inter-operator bias by BCTI with kappa for scoring intensity increasing from
      0.59 to 0.81, indicative of almost perfect agreement. CONCLUSIONS: By application
      of BCTI to the validation of IHC, operator bias and therefore poor
      reproducibility can be identified, characterised and corrected to achieve a level
      of error normally associated with a quantitative biomarker assay, such as an
      ELISA. The methodological approach described herein can be applied to any generic
      IHC technique.

PMID- 24674713
TI  - Fricatives at 18 months as a measure for predicting vocabulary and grammar at 24
      and 30 months.
AB  - PURPOSE: Language develops at variable rates in young children, yet markers for
      different developmental trajectories, have not been identified. Production of
      fricatives in words may be one marker because they are later developing sounds
      and contribute to syntactic production. We examined whether children who produced
      fricatives in words by 18 months had better vocabulary and grammar scores at 18,
      24, and 30 months than children who did not. METHOD: The expressive language
      skills of 37 toddlers who did and did not produce fricatives in words by 18
      months of age were compared at 18, 24 and 30 months of age. RESULTS: Expressive
      vocabulary scores and the use of grammatical markers were significantly better
      for children who produced fricatives by 18 months than for those who did not.
      This effect was consistent across scores at 18, 24, and 30 months. The total
      number of consonants and total number of fricatives produced at 18 months did not
      significantly predict expressive vocabulary scores. CONCLUSIONS: Because the
      children who produced fricatives by 18 months demonstrated better expressive
      language skills than their peers who did not produce fricatives by 18 months, the
      early production of fricatives by toddlers may be a marker of a faster expressive
      language developmental trajectory. LEARNING OUTCOMES: Readers will: (1) describe
      the relationship between early phonological development and early expressive
      lexical development, (2) describe the role of perceptual and motor development in
      speech sound the acquisition, and (3) describe the potential relationship between
      the production of fricatives and expressive language development.

PMID- 24674714
TI  - Succenturiate lobe of placenta with vessel anomaly: a case report of prenatal
      diagnosis and literature review.
AB  - We report the case of a 33-year-old woman with antenatal ultrasound diagnosis of
      succenturiate placental lobe at 33 weeks confirmed by B-flow rendering,
      describing the advantages of the application of color Doppler to diagnosis and
      management of placental anomalies. We searched studies about antenatal diagnosis
      of succenturiate placental lobe, including only cases in which color Doppler was
      used. This case underlines the importance of color Doppler in increasing the
      accuracy of diagnosis and achieving an improved differential diagnosis. 

PMID- 24674715
TI  - Subdividing globally important zones based on data distribution across multiple
      genome fragments.
AB  - In multiple genome fragments, a globally important mode is a zone represented by
      a significant change, where the change has a similar impact on every related
      fragment in the zone. This zone may represent the cancer related genes involved
      in diverse tumors. Globally important zones are characterized by two features:
      (1) there are more data points in globally important zones than in other areas of
      fragments; (2) the data points are distributed evenly on as many genome fragments
      as possible. Globally important zone mining needs to contain the following
      features: (1) independent of data distribution; (2) noise filtering; (3) pattern
      boundary identification; and (4) zone ranking. We have developed a hierarchical
      and density-based method, called GIZFinder (globally important zone finder), to
      detect and rank such zones based on two criteria: distribution width and
      distribution depth. The comparisons on the simulated data shows our method
      performs significantly better than the kernel framework and the sliding window.
      By experimenting on real cancer gene data, we identify 53 novel cancer genes,
      some of which have been proven correct. 

PMID- 24674716
TI  - Productivity, part 2: cloud storage, remote meeting tools, screencasting, speech
      recognition software, password managers, and online data backup.
AB  - It is an opportune time for radiologists to focus on personal productivity. The
      ever increasing reliance on computers and the Internet has significantly changed
      the way we work. Myriad software applications are available to help us improve
      our personal efficiency. In this article, the authors discuss some tools that
      help improve collaboration and personal productivity, maximize e-learning, and
      protect valuable digital data. 

PMID- 24674718
TI  - [Unbearable weight of being: talk about losing weight].

PMID- 24674717
TI  - Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory
      actions in immortalized hypothalamic neurons.
AB  - BACKGROUND: Overnutrition and the ensuing hypothalamic inflammation is a major
      perpetuating factor in the development of metabolic diseases, such as obesity and
      diabetes. Inflamed neurons of the CNS fail to properly regulate energy
      homeostasis leading to pathogenic changes in glucose handling, feeding, and body
      weight. Hypothalamic neurons are particularly sensitive to pro-inflammatory
      signals derived locally and peripherally, and it is these neurons that become
      inflamed first upon high fat feeding. Given the prevalence of metabolic disease,
      efforts are underway to identify therapeutic targets for this inflammatory state.
      At least in the periphery, omega-3 fatty acids and their receptor, G-protein
      coupled receptor 120 (GPR120), have emerged as putative targets. The role for
      GPR120 in the hypothalamus or CNS in general is poorly understood. METHODS: Here
      we introduce a novel, immortalized cell model derived from the rat hypothalamus,
      rHypoE-7, to study GPR120 activation at the level of the individual neuron. Gene
      expression levels of pro-inflammatory cytokines were studied by quantitative
      reverse transcriptase-PCR (qRT-PCR) upon exposure to tumor necrosis factor alpha
      (TNFalpha) treatment in the presence or absence of the polyunsaturated omega-3
      fatty acid docosahexaenoic acid (DHA). Signal transduction pathway involvement
      was also studied using phospho-specific antibodies to key proteins by western
      blot analysis. RESULTS: Importantly, rHypoE-7 cells exhibit a transcriptional and
      translational inflammatory response upon exposure to TNFalpha and express
      abundant levels of GPR120, which is functionally responsive to DHA. DHA
      pretreatment prevents the inflammatory state and this effect was inhibited by the
      reduction of endogenous GPR120 levels. GPR120 activates both AKT (protein kinase
      b) and ERK (extracellular signal-regulated kinase); however, the anti
      inflammatory action of this omega-3 fatty acid (FA) receptor is AKT- and ERK
      independent and likely involves the GPR120-transforming growth factor-beta
      activated kinase 1 binding protein (TAB1) interaction as identified in the
      periphery. CONCLUSIONS: Taken together, GPR120 is functionally active in the
      hypothalamic neuronal line, rHypoE-7, wherein it mediates the anti-inflammatory
      actions of DHA to reduce the inflammatory response to TNFalpha.

PMID- 24674719
TI  - [The trend of obesity and type 2 diabetes mellitus in China and policy
      implications].

PMID- 24674720
TI  - [The effects of a very low carbohydrate diet intervention on improving
      cardiovascular risk factors in obese subjects].
AB  - OBJECTIVE: To investigate the effects of a very low carbohydrate diet (VLCD) on
      improving cardiovascular risk factors in obese individuals. METHODS: A 8-week
      VLCD was given to 35 healthy obese subjects and the control group was consisted
      of 35 healthy volunteers. Multi-cardiovascular risk factors were investigated,
      including weight, waist circumference, BMI, blood pressure, fasting plasma
      glucose (FPG), fasting insulin (FIns), lipid profiles, urinary albumin-creatinine
      ratio (UACR), C-reactive protein (CRP) , TNFalpha and adiponectin. RESULTS: At
      the baseline of the study, compared with the healthy control group, all the
      cardiovascular risk factors were significantly more deteriorated in the obese
      subjects (all P values <0.05). At the end of the study, the obese subjects showed
      significant decrease in their mean weight and waist circumference [(8.5 +/- 0.7)
      kg and (6.6 +/- 1.1)cm, respectively; all P values < 0.01]. Significant decrease
      was also found in the levels of systolic blood pressure (SBP), diastolic blood
      pressure (DBP), FIns, TC and TG (all P values < 0.05), while no significant
      change of FPG, HDL-C and LDL-C. The levels of UACR, CRP and TNFalpha were all
      significantly decreased [(1.86 +/- 0.86) ug/mg, (1.15 +/- 0.45) mg/L and (0.94 +/
      0.21) ng/L, respectively; all P values < 0.05], while the level of adiponectin
      was significantly increased [(2.12 +/- 0.59) mg/L, P < 0.01]. CONCLUSION: VLCD is
      an effective intervention in obese subjects which could improve the
      cardiovascular risk factors by the modest weight loss.

PMID- 24674721
TI  - [The correlation between serum uric acid level and abdominal obesity or metabolic
      syndrome].
AB  - OBJECTIVE: To investigate the relationship between serum uric acid (UA) level and
      abdominal obesity or metabolic syndrome (MS). METHODS: A total of 875 subjects,
      with 350 males and 525 females, aged 40-65 years old, were enrolled in this
      study. The clinical and biochemical data were collected and MRI was used to
      assess the visceral and subcutaneous adipose tissues. The relationships between
      UA level and abdominal obesity or MS were analyzed, and the cut-off values of UA
      for abdominal obesity and MS were determined. RESULTS: Raised risks of abdominal
      obesity(OR = 4.35, 95%CI 1.91-9.90 in males; OR = 5.44, 95%CI 2.41-12.31 in
      females) and MS(OR = 4.47, 95%CI 2.08-9.62 in males; OR = 11.62, 95%CI 3.43-39.37
      in females) were observed with the increase of UA level. The multiple logistic
      regression analysis showed that UA was an independent risk factor for
      hypertriglyceridemia(OR = 2.23, 95%CI 1.02-4.87 in males; OR = 3.04, 95%CI 1.49
      6.23 in females) in all subjects and for abdominal obesity(OR = 3.23, 95%CI 1.32
      7.91) and hypertension (OR = 2.35, 95%CI 1.37-4.05) in the females. Among the
      females, the regression line analyzed by simple correlation indicated that the UA
      level of 244.0 umol/L was corresponded to the visceral adipose tissue area of 80
      cm(2). The optimal cut-off point of UA for the diagnosis of MS was 258.8 umol/L
      determined by the receiver operating characteristic curve. CONCLUSIONS: The level
      of UA is closely correlated with abdominal obesity and MS in the middle-aged
      Chinese. The elevated UA level is an independent risk factor for abdominal
      obesity and MS in the female.

PMID- 24674722
TI  - [A clinical analysis of thyrotropin-secreting pituitary adenomas in 20 patients].
AB  - OBJECTIVE: To explore the clinical characteristics of thyrotropin-secreting
      pituitary adenomas. METHODS: A total of 20 patients with thyrotropin-secreting
      pituitary adenomas hospitalized in Shanghai Huashan Hospital from 2006 to 2013
      were enrolled in the study. The clinical features, hormone levels, imaging
      findings, treatment and follow-up data were reviewed and analyzed. RESULTS: Most
      of the patients were young and middle-aged with (40.0 +/- 14.5) years old. The
      disease duration varied from 1 month to 15 years. Among them, 13 cases (65%)
      presented with thyrotoxicosis and/or thyroid goiters and 9 (45%) presented with
      symptoms of intracranial compression. All patients had unsuppressed levels of
      thyroid stimulating hormone (TSH) with elevated levels of thyroid hormones.
      Pituitary lesions were found in all patients by neuroimaging. Pituitary
      adenomectomy, and/or somatostatin analogs and/or radiotherapy were applied in all
      patients after definitive diagnosis. Restored euthyroidism and shrinks pituitary
      adenomas with no progression were observed in 18 patients. Relapse was found in 1
      patient and another patient was lost to follow up. CONCLUSIONS: Thyrotropin
      secreting pituitary adenomas mainly present with thyrotoxicosis and/or pituitary
      tumor. Comprehensive therapy, including adenomectomy, somatostatin analogues and
      radiotherapy, is often needed for the management.

PMID- 24674723
TI  - [The clinical characteristics of patients with vertebrobasilar dolichoectasia].
AB  - OBJECTIVE: To explore the clinical features of patients with vertebrobasilar
      dolichoectasia (VBD). METHODS: Patients diagnosed with posterior circulation
      ischemia in our hospital from October 2008 to January 2012 were consecutively
      collected and were divided into the VBD group and the non-VBD (NVBD) group.
      Clinical manifestations, risk factors, hemodynamic parameters and neuroimaging
      features were collected. RESULTS: (1) Statistical difference was observed in
      dyslipidemia, hypertension and the history of diabetes in the two groups (P <
      0.05). (2) The cerebral hemodynamic features of the VBD patients were as the
      following: decreased peak systolic velocity of vertebral artery and basilar
      artery and decreased systolic/diastolic ratio. Statistical difference was showed
      in the average peak flow velocity (Vm), pulsatility index (PI) and resistance
      index (RI) (P = 0.036, 0.032, 0.032, respectively). (3) The main clinical
      manifestations of VBD were ischemic cerebrovascular disease, hemorrhagic
      cerebrovascular disease, oppression, brain damage symptoms and hydrocephalus. (4)
      The diagnosis in most of the VBD patients was confirmed by neural imaging and MRI
      was the first choice. CONCLUSION: The VBD patients have relative unique clinical
      features. MRI should be the first choice for neuroimaging.

PMID- 24674724
TI  - [The clinical characteristics and cognitive function of Parkinson's disease
      patients associated with pain].
AB  - OBJECTIVE: To explore the type and etiology of chronic pain in patients with
      Parkinson's disease (PD), and to assess the association between pain and
      cognitive function. METHODS: A total of 116 PD patients were enrolled in the
      study and assessed with the following rating scales: Unified Parkinson's Disease
      Rating Scale (UPDRS), Hoehn-Yahr Scale (H-Y), Hamilton Depression Rating Scale
      for Depression(HRSD), Visual Analogue Scale (VAS) and Montreal Cognitive
      Assessment (MoCA). RESULTS: Compared with PD patients without pain, PD patients
      with pain had higher scores of UPDRS, H-Y and HRSD rating scales. Depression
      (scores of HRSD) was the only factor associated with pain showed by the Logistic
      regression model (P = 0.007). PD patients with pain had lower scores of delayed
      recall (P = 0.020). PD patients with pain happened before their motor symptoms
      had a lower score of delayed recall (P = 0.015). CONCLUSIONS: Musculoskeletal
      pain is the most common type in PD patients with pain. Depression is probably an
      independent risk factor for pain in PD patients. Delayed recall is the dominant
      impaired cognitive function.

PMID- 24674725
TI  - [The role of Foxo1 and ubiquitin-proteasome system markers in muscle atrophy
      caused by chronic kidney disease].
AB  - OBJECTIVE: To identity whether there is muscle atrophy phenomenon in end-stage
      kidney disease patients and to detect the level of transcription factor Foxo1 and
      the activity of ubiquitin-proteasome system. METHODS: Twenty-two patients in
      chronic kidney disease (CKD) stage 5 were selected and their mean muscle cross
      sectional area was measured. mRNA and protein levels of Foxo1, Atrogin-1, MuRF1
      in rectus abdominis biopsies obtained from consecutive patients were detected.
      Control biopsies were obtained from 8 healthy subjects during elective surgery
      for abdominal wall hernias and 6 subjects during elective surgery for
      adenomyosis. RESULTS: Compared with the control group, cross sectional area of
      muscle fibers decreased and the transcription and protein levels of Foxo1,
      Atrogin-1, MuRF1 were upregulated in CKD group (P < 0.05). Protein level of p
      Foxo1 decreased in CKD group (P < 0.05). CONCLUSION: There exist muscle atrophy
      phenomenon in CKD patients, which may associate with the upregulation of Foxo1
      and activation of ubiquitin-proteasome system.

PMID- 24674727
TI  - [Predictors of efficacy of biofeedback therapy in patients with chronic
      constipation].
AB  - OBJECTIVE: To explore the anorectal physiology, psychological state, quality of
      life, lifestyle of patients with chronic constipation (CC) and evaluate the
      factors which potentially predict the efficacy of biofeedback therapy (BF).
      METHODS: Seventy CC patients receiving BF training were enrolled in this study.
      Anorectal physiology, Zung's Self-Rating Depression Scale (SDS), Zung's Self
      Rating Anxiety Scale (SAS) and Chinese version of the MOS 36-item short form
      healthy survey (SF-36), lifestyle scale were recorded before BF training. A bowel
      symptom measurement including five major symptoms was recorded before and after
      BF training. The improvement in the symptom score was considered as criteria of
      clinical efficacy of BF therapy. Thirty-two possible influencing factors of
      efficacy of BF therapy were selected. Univariate analysis and multivariate
      analysis were conducted to assess the independent predictors. RESULTS: The
      results of univariate analysis showed that efficacy of BF therapy was positively
      correlated to the role physical (r = 0.256, P = 0.031), negatively correlated to
      the score of SDS (r = -0.315, P = 0.007) and the first sensation threshold (r = 
      0.278, P = 0.020). The multivariate analysis showed the score of SDS (beta = 
      0.263, P = 0.033) and the first sensation volume (beta = -0.281, P = 0.013) were
      the independent predicator of efficacy of BF therapy. CONCLUSION: CC patients who
      tended to depression state and rectal hyposensitivity have poor response to BF
      therapy. To treat these patients purposely could optimize the efficacy of BF
      therapy.

PMID- 24674726
TI  - [A comparison of clinical characteristics and prognosis of adult acute graft
      versus-host disease between human leukocyte antigen- identical and -mismatched
      allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To compare the clinical characteristics and prognosis of acute graft
      versus-host disease (aGVHD) between patients undergoing human leukocyte antigen
      (HLA)-identical and HLA-mismatched allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). METHODS: Clinical data of 544 patients receiving
      related allo-HSCT in Institute of Hematology of Peking University from January
      2010 to December 2011 were retrospectively analyzed. The clinical features of
      aGVHD including manifestations and prognosis between HLA-identical and HLA
      mismatched transplantation were compared. RESULTS: The cumulative incidence of
      aGVHD in related HLA-mismatched transplant was 50.2%, which was significantly
      higher than that of HLA-identical transplant (20.4%, P < 0.001). However, the
      cumulative incidence of grade III degrees -IV degrees  aGVHD between the two
      groups was comparable (4.5% vs 6.8%, P = 0.066). Gut aGVHD accounted for 31.1% in
      HLA-identical transplant while cutaneous aGVHD was the dominant area in HLA
      mismatched transplant (66.5%). The incidence of gut and liver aGVHD in HLA
      mismatched patients was also lower than that in HLA-identical patients. The
      proportion of patients with aGVHD accompanied by fever was higher in HLA
      mismatched patients than in HLA-identical patients (47.6% vs 28.9%, P = 0.028).
      The cure rate of aGVHD in identical transplant was lower than that in mismatched
      transplant, especially for grade III degrees -IV degrees  aGVHD. The complete
      remission rate after second-line anti-GVHD therapies was lower than that of
      mismatched transplant (88.9% vs 98.8%, P = 0.006). More patients died of aGVHD in
      identical transplant compared with mismatched transplant (11.1% vs 2.4%, P =
      0.024). CONCLUSION: More patients who received HLA-mismatched allo-HSCT develop
      into aGVHD compared with HLA-identical transplant. But the incidence of severe
      aGVHD between HLA-identical and -mismatched is comparable. The overall cure rate
      of HLA-mismatched transplant is significantly higher than that of HLA-identical
      transplant.

PMID- 24674728
TI  - [A clinical analysis of ocular involvement in 111 cases of Behcet's disease].
AB  - OBJECTIVE: To study the ocular manifestations in patients with Behcet's
      disease(BD). METHODS: Medical records at Peking Union Medical College Hospital
      from 2002 to 2012 were reviewed to identify the patients who were diagnosed as BD
      with ocular involvement. RESULTS: One hundred and eleven BD patients developed
      ocular involvement. Males were more frequently involved, and the male/ female
      ratio was 2.08: 1. The age at the onset of BD and the time of ocular involvement
      were (27.6 +/- 10.8) and (31.5 +/- 10.7) years, respectively. The median interval
      between the diagnosis of BD and ocular disease was 24 (0, 372) months. Ocular
      involvement was bilateral in 85.6% patients. About two thirds patients (66.7%)
      had impaired vision, for example, visual acuity of 0.1 or less was detected in
      60.4% patients. Uveitis (90.1%) was the most common findings in BD patients with
      ocular involvement and the most frequent type of uveitis in both sexes was
      panuveitis (62.16%). Vision loss, proliferative retinopathy and cataract were
      more common in men. There was a statistically significantly higher frequency of
      positive human leukocyte antigen(HLA)-B51 in the male BD with ocular involvement
      than in the female. All BD patients with uveitis were given systemic
      corticosteroid or combined immunosuppressive agents. The improvement of visual
      acuity was seen in 77% BD patients, but the recurrent attacks occurred in 49%
      patients, resulting in blindness in 25.5% of them. TNFalpha blockers were given
      to 19 recurrent uveitis patients, 12 patients improved while two had no response.
      CONCLUSIONS: The most common ocular involvement in BD was uveitis. Males were
      more frequently involved with a more severe disease, higher complications and
      positive HLA-B51 than in females. Glucocorticoids and immunosuppressants were
      effective to uveitis, but high rate of recurrent inflammatory ocular attacks led
      to high risk of blindness. TNFalpha blockers may improve the outcome of recurrent
      BD uveitis.

PMID- 24674729
TI  - [Effects of sucralfate and acid-suppressive drugs on preventing ventilator-
      associated pneumonia of mechanically ventilated patients: a meta-analysis].
AB  - OBJECTIVE: To evaluate the effect of sucralfate and acid-suppressive drugs on
      preventing ventilator-associated pneumonia (VAP) in mechanically ventilated
      patients. METHODS: All randomized controlled trials (RCTs), which studied the
      effect of sucralfate and acid-suppressive drugs on the incidence of VAP in
      mechanically ventilated patients, were searched from PubMed, Embase and the
      Cochrane Library during January 1966 to March 2013 via manual and computer
      retrieval. All related data were extracted. Meta analysis was conducted using the
      statistical software RevMan 5.2 and the quality of the RCTs was strictly
      evaluated with the methods recommended by the Cochrane Collaboration. RESULTS: A
      total of 15 RCTs involving 1315 patients in the sucralfate group and 1568
      patients in the acid-suppressive drug group were included in this study. The
      incidence of VAP was significantly reduced in the sucralfate group (RR = 0.81,
      95%CI 0.7-0.95, P = 0.008), while no difference was found between the two groups
      in the incidence of stress-related gastrointestinal bleeding (RR = 0.96, 95%CI
      0.59-1.58, P = 0.88). No statistical difference was found in the days on
      ventilator, duration of ICU stay and ICU mortality in the two groups (all P
      values > 0.05). CONCLUSION: In patients with mechanical ventilation, sucralfate
      could decrease the incidence of VAP, while has no such effect on the stress
      related gastrointestinal bleeding, the days on ventilator, duration of ICU stay
      and ICU mortality.

PMID- 24674731
TI  - Effects of micro-arc oxidation coating on outcomes of a cementless grit-blasted
      tapered-wedge stem in total hip arthroplasty.
AB  - To evaluate the effects of micro-arc oxidation (MAO) coating on the outcomes of a
      grit-blasted tapered-wedge stem in total hip arthroplasty (THA), we performed a
      retrospective review of 141 THAs using MAO coated stem for a minimum of 5years
      and compared them to 219 THAs using the same geometry stem without MAO coating.
      Harris hip score improved from 43.7 points preoperatively to 93.9 points
      postoperatively. No hips were revised for aseptic loosening. Complications
      included one squeaking hip, one iliopsoas tendonitis, and one deep vein
      thrombosis. Postoperative Harris hip scores, WOMAC scores, UCLA activity scores,
      stem stabilities, and complication rates did not differ between the groups. After
      medium-term follow-up, our findings did not support the use of MAO coating on
      grit-blasted tapered-wedge stem to improve clinical outcomes.

PMID- 24674730
TI  - Bariatric surgery prior to total joint arthroplasty may not provide dramatic
      improvements in post-arthroplasty surgical outcomes.
AB  - This study compared the total joint arthroplasty (TJA) surgical outcomes of
      patients who had bariatric surgery prior to TJA to TJA patients who were
      candidates but did not have bariatric surgery. Patients were retrospectively
      grouped into: Group 1 (n = 69), those with bariatric surgery >2 years prior to
      TJA, Group 2 (n = 102), those with surgery within 2 years of TJA, and Group 3 (n
      = 11,032), those without bariatric surgery. In Group 1, 2.9% (95% CI 0.0-6.9%)
      had complications within 1 year compared to 5.9% (95% CI 1.3%-10.4%) in Group 2,
      and 4.1% (95% CI 3.8%-4.5%) in Group 3. Ninety-day readmission (7.2%, 95% CI 1.1%
      13.4%) and revision density (3.4/100 years of observation) was highest in Group
      1. Bariatric surgery prior to TJA may not provide dramatic improvements in post
      operative TJA surgical outcomes.

PMID- 24674732
TI  - Is the newest fibrin sealant an effective strategy to reduce blood loss after
      total knee arthroplasty? A randomized controlled study.
AB  - An RCT was conducted to ascertain whether, compared to control management,
      topical application of a novel fibrin sealant (Evicel, J&J) in patients
      undergoing primary TKA reduces peri-operative blood loss. Sixty-two patients were
      randomized to receive topical application of Evicel (N = 31) or not (N = 31). The
      mean total blood loss was 1.9L(+/- 0.7) in the control group and 1.8L(+/- 0.5) in
      the treatment group (P = 0.4). The transfusion rate was 32.3% in the control
      group and 25.8% in the treatment group (P = 0.5). The transfusion rate decreased
      linearly with increasing preoperative Hb levels in the treatment group (P =
      0.005). The results of this study suggest that topical application of this novel
      fibrin sealant doesn't reduce perioperative blood loss and the need for
      allogeneic blood transfusion.

PMID- 24674733
TI  - No differences found in bearing related hip survivorship at 10-12 years follow-up
      between patients with ceramic on highly cross-linked polyethylene bearings
      compared to patients with ceramic on ceramic bearings.
AB  - At a minimum follow-up of ten years we compared clinical and radiographic
      findings and survivorship in a cohort of 412 patients (447 hips) who received
      alumina on alumina CoC bearings to findings from a cohort of 216 patients (228
      hips) with alumina on highly cross-linked polyethylene (HXLPE) bearings. All
      patients were operated for osteoarthritis. With bearing-related complications as
      endpoint, analysis showed no significant difference in survivorship between
      cohorts (99.8% for the CoC vs. 99.4% for HXLPE). In addition, there were no
      significant differences in clinical and radiographic findings between cohorts. We
      concluded that alumina on HXLPE bearings are a reasonable lower cost alternative
      to ceramic on ceramic bearing couples. 

PMID- 24674734
TI  - Uncemented total hip arthroplasty using a tapered femoral component in obese
      patients: an 18-27 year follow-up study.
AB  - The purpose of this study was to evaluate the efficacy of an uncemented tapered
      femoral component in obese patients at a mean follow-up of 23 years. We
      retrospectively reviewed 119 consecutive uncemented total hip arthroplasties in
      105 obese patients using a tapered femoral component between 1983 and 1987. The
      mean body mass index of these patients was 34 (range 30-47). Complete clinical
      and radiographic follow-up was obtained on the 55 hips in 47 patients who
      survived a minimum of 18 years (range 18-27 years). Three femoral components (6%)
      have been revised, none for aseptic loosening. One was loose by radiographic
      criteria. These results demonstrate that an uncemented tapered stem can provide
      excellent fixation in obese patients out to 27 years.

PMID- 24674735
TI  - Health-related quality of life in adolescents with congenital heart disease.
AB  - PURPOSE: This study aims to evaluate the health-related quality of life of
      adolescents with congenital heart disease, describing health-related quality of
      life according to the diagnosis and severity of congenital heart disease,
      identified by variables such as the presence of symptoms, surgical interventions,
      use of medication, and residual lesion. METHODS: A cross-sectional study was
      conducted on 203 adolescents with congenital heart disease attended at the
      Pediatric Cardiology ambulatory of a reference hospital in Brazil. The Brazilian
      version of the questionnaire KIDSCREEN-27 was used for the assessment of health
      related quality of life. Information related to the congenital heart disease
      diagnosis and clinical variables were collected from the medical records of the
      patients. RESULTS: There was no statistically significant difference between
      acyanotic and cyanotic groups, as well as for the different diagnosis of
      congenital heart disease. A trend for better health-related quality of life in
      the dimension of Psychological Well-Being (p=0.054) was found in the groups with
      surgical intervention and use of medication. Adolescents that referred a good
      general health presented significantly better results in all dimensions of health
      related quality of life, except for Autonomy and Parent Relation, than those who
      presented clinical symptoms (p<0.05). CONCLUSIONS: Type of congenital heart
      disease and initial diagnosis did not seem to affect the perception of health
      related quality of life, corroborating findings of several studies. Surgical
      interventions and the use of medication can improve previous clinical status, and
      therefore it seems to be beneficial in terms of Psychological Well-Being. The
      presence of clinical symptoms was the variable that caused the largest impact on
      the perception of health-related quality of life, possibly because of the
      impairment they bring to the daily lives of these patients.

PMID- 24674736
TI  - Bandwidths for the perception of head orientation decrease during childhood.
AB  - Adults use the orientation of people's heads as a cue to the focus of their
      attention. We examined developmental changes in mechanisms underlying sensitivity
      to head orientation during childhood. Eight-, 10-, 12-year-olds, and adults were
      adapted to a frontal face view or a 20 degrees  left or right side view before
      judging the orientation of a face at or near frontal. After frontal adaptation,
      there were no age differences in judgments of head orientation. However, after
      adaptation to a 20 degrees  left or right side view, aftereffects were larger and
      sensitivity to head orientation was lower in 8- and 10-year-olds than in adults,
      with no difference between 12-year-olds and adults. A computational model
      indicates that these results can be modeled as a consequence of decreasing neural
      tuning bandwidths and decreasing additive internal noise during childhood, and/or
      as a consequence of increasing inhibition during childhood. These results provide
      the first evidence that neural mechanisms underlying sensitivity to head
      orientation undergo considerable refinement during childhood.

PMID- 24674737
TI  - Mothers requiring dialysis: parenting and end-stage kidney disease.
AB  - BACKGROUND: Mothers requiring dialysis to treat end-stage kidney disease face the
      challenging demands of the disease and dialysis treatment in addition to their
      role as a parent. OBJECTIVE: To describe the experience of mothers who require
      haemodialysis. METHODS: Four mothers receiving haemodialysis treatment for end
      stage kidney disease in regional Australia were interviewed to explore the
      mothers' experiences, attitudes, beliefs and values of their dual role as mothers
      and haemodialysis recipients. RESULTS: The overarching theme emerging from the
      data was the competing roles of motherhood and dialysis. Four key sub-themes
      emerged: fitting everything in, internal family challenges, lost connections and
      striving for normality. CONCLUSION: Being a mother adds a range of complexities
      to being on dialysis. While managing dialysis, mothers struggle to care for their
      children and stay connected with family life. Nephrology health professionals are
      uniquely placed to support mothers and need to develop strategies to ease their
      burdens of care.

PMID- 24674739
TI  - Psychological and behavioral adjustment in female youths with high or low
      psychopathic traits.
AB  - The aim of the present study was to analyze the role of psychopathic traits in
      female juvenile delinquency. Using a sample of 236 young females from the
      Juvenile Detention Centers of the Portuguese Ministry of Justice and schools in
      the Lisbon area, a group of female youths with high psychopathic traits (n=118;
      M=15.84 years of age; range=14-18 years of age) and a group of female youths with
      low psychopathic traits (n=118; M=15.77 years of age; range=14-18 years of age)
      were formed based on the Portuguese version of the Antisocial Process Screening
      Device-Self-report (APSD-SR). The results showed that young females with high
      psychopathic traits start engaging in criminal activities and come into contact
      with the justice system earlier in life; exhibit higher levels of behavioral
      problems, conduct disorder, delinquent behaviors and serious criminality; and
      demonstrate lower levels of self-esteem and pro-social behavior. The importance
      of some variables in predicting group membership (high versus low psychopathic
      traits) was established through a binary logistic regression. Our findings
      reinforce the importance of the psychopathy construct for the early
      identification of potentially high-risk female youths and for the assessment of
      female youths who have already come into contact with the judicial system.

PMID- 24674738
TI  - Enhancer RNAs and regulated transcriptional programs.
AB  - A large portion of the human genome is transcribed into RNAs without known
      protein-coding functions, far outnumbering coding transcription units. Extensive
      studies of long noncoding RNAs (lncRNAs) have clearly demonstrated that they can
      play critical roles in regulating gene expression, development, and diseases,
      acting both as transcriptional activators and repressors. More recently,
      enhancers have been found to be broadly transcribed, resulting in the production
      of enhancer-derived RNAs, or eRNAs. Here, we review emerging evidence suggesting
      that at least some eRNAs contribute to enhancer function. We discuss these
      findings with respect to potential mechanisms of action of eRNAs and other ncRNAs
      in regulated gene expression. 

PMID- 24674740
TI  - [Never it is too late to improve our habits].

PMID- 24674741
TI  - Antimicrobial resistance monitoring projects for zoonotic and indicator bacteria
      of animal origin: common aspects and differences between EASSA and EFSA.
AB  - Resistance monitoring programmes are essential to generate data for inclusion in
      the scientific risk assessment of the potential for transmission of antimicrobial
      resistant bacteria or their resistance determinants from food-producing animals
      to humans. This review compares the technical specifications on monitoring of
      antimicrobial resistance in zoonotic Salmonella, Campylobacter and indicator
      Escherichia coli and Enterococcus as performed by the European Food Safety
      Authority (EFSA) with veterinary pharmaceutical industry's European Antimicrobial
      Susceptibility Surveillance in Animals (EASSA) programme. The authors conclude
      that most of EFSA's recent monitoring recommendations have been covered by EASSA
      since the start of the latter programme in 1998. The major difference between the
      two programmes is the classification into 'susceptible' versus 'resistant'. While
      EFSA categorises all isolates with an MIC value above the epidemiological cut-off
      value as 'resistant', EASSA differentiates between 'percentage decreased
      susceptible' and 'percentage clinical resistant' strains by applying both
      epidemiological cut-off values and clinical breakpoints. Because there is still a
      need to further improve harmonisation among individual EU Member State
      activities, Animal Health Industry welcomes EFSA's initiative to further improve
      the quality of resistance monitoring as it is of utmost importance to apply
      standardised collection procedures and harmonised susceptibility testing, when
      monitoring antimicrobial resistance across Europe. 

PMID- 24674742
TI  - Immunogenicity of Staphylococcus aureus LukM/F'-PV recombinant subunits:
      validation of diagnostic potential and evaluation of protective efficacy in
      vitro.
AB  - Leukotoxin M/F'-Panton Valentine (LukM/F'-PV), a beta pore-forming toxin secreted
      by Staphylococcus aureus, is a major virulence factor involved in the
      pathogenesis of bovine mastitis. The present study was aimed to determine
      immunogenicity of two recombinant subunits of LukM/F'-PV, rLukM (MW 38 kDa) and
      rLukF (MW 39 kDa), develop and validate an indirect enzyme linked immunosorbent
      assay (ELISA) using polyclonal antibodies raised in rabbits, and evaluate
      applicability of the assay to diagnose clinical and subclinical bovine mastitis.
      Additionally, in vitro assays were conducted to determine abilities of antibodies
      to neutralize cytotoxicity of the native leukotoxin. A total of 87 bovine milk
      samples (healthy, subclinical and clinical mastitis) were evaluated for the
      presence of toxin determinants. Receiver-operator characteristic curve for the
      experimental ELISA values statistically interpreted a cut-off score of >0.109
      OD405, with an assay specificity of 100% and sensitivity in the range of 80
      87.5%. In addition, area under curve of 0.93-0.98 revealed the test was accurate
      in categorizing samples from infected and non-infected bovine. The rLukF IgG
      ELISA was more sensitive than rLukM IgG-ELISA. Furthermore, it was evident from
      MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium) dye reduction,
      indirect immunofluorescence and lactate dehydrogenase assays that anti
      rLukM/rLukF antibodies, with high neutralizing titers, inhibited in vitro
      leukotoxic activity and protected bovine neutrophil membrane integrity from
      cytotoxicity of native leukotoxin. The findings demonstrated that antibodies
      produced from recombinant subunits contribute to specific and sensitive
      immunodiagnosis and may also have the potential to provide passive therapeutic
      benefit in the management of bovine mastitis.

PMID- 24674743
TI  - Development of a novel pulse wave velocity measurement system: using dual
      piezoelectric elements.
AB  - The aim of this study is to develop a painless system of measuring the brachial
      ankle arterial pulse wave velocity (baPWV) without compression cuffs. The PWV
      reflects the compliance of the artery and is measured for the early diagnosis of
      arteriosclerotic vascular diseases. However, the conventional baPWV system, which
      measures four cuff pressures simultaneously, easily causes circulation block and
      tightening pain at the extremities. In addition, approximately 15 min are
      required to stabilise the blood pressure for re-examination. Therefore, we
      developed a novel baPWV measurement system using dual piezoelectric sensor
      elements. The principle of this high-sensitivity pressure pulse detection system
      is based on adding the two in-phase outputs from the coaxially arranged dual
      piezoelectric sensor. As our system facilitates the measurement of the baPWV by
      detecting the pulsation of an artery using sensors fixed on the skin where the
      pulse is palpable, it does not cause pain and reduces examination time. The
      coefficients of correlation between the baPWV values obtained from the
      conventional and present methods were 0.93 (right side) and 0.90 (left side). The
      results suggest that our system can be used to measure the baPWV without pressure
      cuffs as accurately as the conventional method.

PMID- 24674744
TI  - Optical tracking of local surface wave for skin viscoelasticity.
AB  - Rapid and effective determination of biomechanical properties is important in
      examining and diagnosing skin thermal injury. Among the methods used,
      viscoelasticity quantification is one of the most effective methods in
      determining such properties. This study aims to rapidly determine skin
      viscoelasticity by optically tracking the local surface wave. New elastic and
      viscous coefficients were proposed to indicate skin viscoelasticity based on a
      single impulse response of the skin. Experiments were performed using fresh
      porcine skin samples. Surface wave was generated in a single impulse using a
      vibrator with a ball-tipped device and was detected using a laser Doppler
      vibrometer. The motions along the depth direction were monitored using an
      ultrasound system. The ultrasound monitoring results indicated the multi-layered
      viscoelasticity of the epidermis and dermis. The viscoelastic coefficients from
      four healthy samples show a potential viscoelasticity variation of porcine skin.
      In one sample, the two coefficients were evidently higher than those in a healthy
      area if the skin was slightly burned. These results indicate that the proposed
      method is sensitive, effective, and quick in determining skin viscoelasticity. 

PMID- 24674746
TI  - Coronary endarterectomy: new flavors from old recipes.
AB  - Coronary endarterectomy is an old surgical procedure against coronary artery
      disease first described by Baily et al. in 1957. Despite its first adverse
      results, several current publications have shown that coronary endarterectomy
      with on-pump or off-pump coronary artery bypass grafting can be safely performed
      with acceptable mortality, morbidity, and angiographic patency rates. Coronary
      endarterectomy can assure complete revascularization supplying the myocardium
      with satisfactory blood flow in cases of a diffusely diseased left anterior
      descending artery or diffuse calcification, thus preventing residual ischemia.
      Hence, it is important to evaluate current results, rethink this old recipe, and
      redefine its indications. 

PMID- 24674745
TI  - Forgetfulness during aging: an integrated biology.
AB  - Age-related impairments in memory are often attributed to failures, at either
      systems or molecular levels, of memory storage processes. A major characteristic
      of changes in memory with increasing age is the advent of forgetfulness in old
      vs. young animals. This review examines the contribution of a dysfunction of the
      mechanisms responsible for modulating the maintenance of memory in aged rats. A
      memory-modulating system that includes epinephrine, acting through release of
      glucose from liver glycogen stores, potently enhances memory in young rats. In
      old rats, epinephrine loses its ability to release glucose and loses its efficacy
      in enhancing memory. Brain measures of extracellular levels of glucose in the
      hippocampus during memory testing show decreases in glucose in both young and old
      rats, but the decreases are markedly greater in extent and duration in old rats.
      Importantly, the old rats do not have the ability to increase blood glucose
      levels in response to arousal-related epinephrine release, which is retained and
      even increased in aged rats. Glucose appears to be able to reverse fully the
      increased rate of forgetting seen in old rats. This set of findings suggests that
      physiological mechanisms outside of the brain, i.e. changes in neuroendocrine
      functions, may contribute substantially to the onset of rapid forgetting in aged
      animals. 

PMID- 24674747
TI  - Serial intravascular ultrasound assessment of very late stent thrombosis after
      sirolimus-eluting stent placement.
AB  - PURPOSE: In-stent restenosis has been decreasing through the introduction of drug
      eluting stents (DES). On the other hand, adverse events such as very late stent
      thrombosis (VLST) and late catch-up phenomenon can occur especially with
      sirolimus-eluting stents (SES, first-generation DES) in long-term follow-up.
      However, the precise mechanisms underlying VLST have not been well investigated
      in vivo. METHODS AND RESULTS: From 2004 to 2010, 2034 SES were implanted in 1656
      patients and caused eight VLST (0.48% per patient) at Fukuoka Tokushukai Medical
      Center. Of these, serial intravascular ultrasound (IVUS) images (post-stent
      implantation and at the time of VLST onset) were obtained from three patients
      with VLST. Comparing them with eight control patients with SES implanted, the
      vascular reactivity of VLST patients was analyzed. Eight VLST happened 50 +/- 15
      months after stent implantation and three of the eight patients with VLST had not
      taken aspirin daily. There were no differences in minimum stent area, maximum
      external elastic membrane (EEM) area, and stent edge (distal and proximal) EEM
      area in post-procedural IVUS images. Compared with the control group patients,
      DeltaEEM area (10.6 +/- 3.4mm(2) vs. 1.7 +/- 1.9 mm(2), p=0.01) and vessel
      expansion ratio (185.6 +/- 40.3% vs. 112.0 +/- 12.1%, p=0.01) were significantly
      greater in the VLST group based on the greater peri-stent plaque expansion (262.1
      +/- 72.8% vs. 118.7 +/- 21.2%, p=0.01). CONCLUSION: Our serial IVUS study showed
      that the vascular positive remodeling after SES implantation is one of the most
      probable morphological mechanisms for VLST development.

PMID- 24674748
TI  - Percutaneous closure of postinfarct muscular ventricular septal defects: a
      multicenter study in China.
AB  - BACKGROUND: Surgical repair is an effective method to treat ventricular septal
      defect (VSD) complicating acute myocardial infarction (AMI). However, the
      mortality rate remains high. This study was designed to assess the immediate and
      mid-term results of transcatheter closure of postinfarct muscular VSDs. METHODS:
      Data were retrospectively collected from 42 AMI patients who underwent attempted
      transcatheter VSD closure between 2008 and 2012 in seven heart centers of China.
      RESULTS: Nine patients underwent emergent VSD closure in the acute phase (within
      two weeks from VSD) while the others underwent elective closure. The time between
      VSD occurrence and closure in emergency group and elective group was 7.7 +/- 2.3
      days and 35 +/- 14.5 days, respectively (p<0.01). The percentage of procedure
      success in the emergency group and elective group was 77.8% (7/9) and 97%
      (32/33), respectively (p=0.048). The hospital mortality was higher for emergent
      closure in comparison to elective closure (66.7% vs. 6.1%, p<0.01). During a
      median follow-up of 25 months (0-58 months), two patients died at 8 and 29
      months, respectively, and no serious complications occurred in other patients.
      CONCLUSION: Interventional postinfarct VSD closure is a safe and effective
      approach that can be performed with a high procedural success rate, with
      favorable outcomes if it can be undertaken >14 days postinfarct.

PMID- 24674749
TI  - Twelve weeks of smoking cessation therapy with varenicline increases the serum
      levels of apolipoprotein A-I only in the success group.
AB  - BACKGROUND: Cigarette smoking adversely affects lipid profiles, and smoking
      cessation should improve lipid profiles in the long term. However, it remains
      unclear whether intensive, medication-based smoking cessation therapy can affect
      lipid profiles in the short term. Thus, we evaluated the short-term effects of
      smoking cessation therapy with varenicline on lipid profiles. METHODS:
      Participants included 86 consecutive subjects who received 12 weeks of smoking
      cessation therapy. All subjects were treated with varenicline, and no changes
      were made to their current lipotropic and antidiabetic medications during
      treatment. At first and last visits, lipid profiles and fasting blood glucose and
      hemoglobin A1c levels were evaluated and physical examination was performed. The
      success group, comprising subjects who attained exhaled carbon monoxide-confirmed
      4-week continuous abstinence, included 69 subjects, whereas the failure group,
      comprising those who did not achieve complete smoking cessation, included 17
      subjects. The number of cigarettes consumed per day was reduced in all subjects
      in the failure group. RESULTS: Serum apolipoprotein A-I (apoA-I) and high-density
      lipoprotein cholesterol (HDL-C) levels significantly increased from baseline to
      12 weeks in the success group (apoA-I: 151.7 +/- 28.0 vs. 158.6 +/- 27.3 mg/dL,
      respectively, p<0.01; HDL-C: 54.6 +/- 15.7 vs. 57.9 +/- 14.3 mg/dL, respectively,
      p<0.01); however, there were no statistically significant differences observed in
      the failure group (apoA-I, 145.9 +/- 33.4 vs. 146.8 +/- 34.2 mg/dL, respectively,
      p=0.87; HDL-C, 52.6 +/- 15.7 vs. 53.3 +/- 16.3 mg/dL, respectively, p=0.80). The
      effect sizes (Cohen's d) of apoA-I and HDL-C in the success group were 0.42 and
      0.46, respectively. The post hoc statistical power values of apoA-I and HDL-C in
      the success group were 0.94 and 0.96, respectively. CONCLUSION: These findings
      suggest that successful smoking cessation therapy with varenicline improves serum
      apoA-I and HDL-C levels in the short term.

PMID- 24674750
TI  - CELSR2-PSRC1-SORT1 gene expression and association with coronary artery disease
      and plasma lipid levels in an Asian Indian cohort.
AB  - BACKGROUND: Genetic regulation of plasma lipids has been shown to influence the
      risk of coronary artery disease (CAD). We analyzed the relationship between
      rs599839 and rs646776 single nucleotide polymorphisms (SNPs) present in the
      CELSR2-PSRC1-SORT1 gene cluster, candidate gene expression, and their association
      with CAD and circulating lipid levels in a representative cohort of Asian Indians
      selected from the Indian Atherosclerosis Research Study. METHODS: SNPs rs599839
      and rs646776 were genotyped by Taqman assay in 1034 CAD patients (cases) and 1034
      age- and gender-matched controls. Expression of CELSR2, PSRC1, and SORT1 genes
      was measured in 100 cases and 100 controls. Plasma levels of total cholesterol
      (TC), triglycerides, high-density lipoprotein-cholesterol, and low-density
      lipoprotein-cholesterol (LDL-c) were measured by enzymatic assay. RESULTS: Both
      rs646776 and rs599839 were in strong linkage disequilibrium (r = 0.98) and showed
      significant protective association with CAD (OR = 0.315, 95% CI 0.136-0.728,
      p<0.007 and OR = 0.422, 95% CI 0.181-0.981, p = 0.045, respectively). Haplotype
      TA showed 72% frequency and was associated with CAD (OR 0.77, 95% CI 0.67-0.88, p
      = 0.0002). PSRC1 gene expression was lower in the cases than in the controls
      (0.75 +/- 0.405 versus 1.04 +/- 0.622, p = 2.26 * 10(-4)). The homozygous variant
      and heterozygous genotypes showed 30% and 15% higher PSRC1 expression,
      respectively. Correspondingly, the minor alleles were associated with lower
      plasma TC and LDL-c levels. CONCLUSION: PSRC1 in the cholesterol gene cluster
      shows a significant association with CAD by virtue of the two SNPs, rs646776 and
      rs599839 that also regulate plasma cholesterol levels.

PMID- 24674751
TI  - Cardiovascular function and prognosis of patients with heart failure coexistent
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) often coexists with
      heart failure (HF), and is considered to be associated with adverse outcomes in
      HF patients. However, the features of cardiovascular function and the detailed
      all-cause mortality of HF with COPD remain unclear. METHODS AND RESULTS:
      Consecutive 378 patients admitted for HF who underwent spirometry were divided
      into three groups: HF without COPD (non-COPD group, n=272), HF with mild COPD
      (GOLD I group, n=82), and HF with moderate COPD (GOLD II group, n=24). The GOLD
      II group, as compared to non-COPD group, had (1) higher troponin T (p=0.009); (2)
      greater cardio-ankle vascular index (p=0.032); and (3) similar cardiac systolic
      and diastolic function of the right and left ventricle. In addition, rates of
      cardiac (p=0.049), non-cardiac (p=0.001), and all-cause mortality (p=0.002) were
      higher in GOLD II group than in non-COPD and GOLD I groups. Importantly, in the
      Cox proportional hazard analyses, the GOLD stage II was an independent predictor
      of cardiac (p=0.038), non-cardiac (p=0.036), and all-cause mortality (p=0.015) in
      HF patients. CONCLUSIONS: HF patients with coexistent moderate COPD (GOLD stage
      II) have greater myocardial damage, greater arterial stiffness, and higher
      cardiac and non-cardiac mortality.

PMID- 24674752
TI  - Clinical significance of left ventricular apical aneurysms in hypertrophic
      cardiomyopathy patients: the role of diagnostic electrocardiography.
AB  - OBJECTIVES: Some patients with hypertrophic cardiomyopathy (HCM) develop left
      ventricular apical aneurysm, leading to serious cardiovascular complications. The
      aims of this study were to identify the incidence and clinical course of HCM
      patients with apical aneurysms in Japan, and to evaluate the role of
      electrocardiography (ECG) as a screening test to detect apical aneurysms in HCM
      patients. METHODS AND RESULTS: In a retrospective, single center analysis of a
      population of 247 HCM patients, 21 patients (8.5%) had left ventricular apical
      aneurysms. Their mean age was 60 +/- 14 years (range: 23-77 years) at study
      entry. Over 4.7 +/- 3.3 years of follow-up, 10 patients (47.6%) experienced an
      adverse clinical event (annual event rate: 10.1%/y), including five implantable
      cardioverter-defibrillator (ICD) implantations for ventricular
      tachycardia/ventricular fibrillation (VT/VF), an appropriate discharge of ICD for
      VT/VF, and four nonfatal thromboembolic strokes. Two patients developed systolic
      dysfunction (ejection fraction <50%). No sudden cardiac death or progressive
      heart failure was detected. Fourteen patients showed ST-segment elevation (>= 1
      mm) in V3 through V5 of ECG. In four patients, progression of the ST-segment
      elevation was recognized. When the ST-segment elevation was used to identify
      apical aneurysms in HCM patients, the sensitivity was 66.7%, and the specificity
      was 98.7%. CONCLUSION: Apical aneurysms in HCM patients in Japan are not rare,
      and are associated with serious cardiovascular complications. The early diagnosis
      of apical aneurysms can be achieved by serial ECG.

PMID- 24674753
TI  - Dose response and clonal variability of lentiviral tetracycline-regulated vectors
      in murine hematopoietic cells.
AB  - Tetracycline-regulated integrating vectors allow pharmacologically controlled
      genetic modification of murine and human hematopoietic stem cells and provide the
      opportunity for time- and dose-controlled reversible transgene expression in
      hematopoietic stem cells in vitro and in vivo. However, the background activity
      of tetracycline-regulated promoters (tetPs) in the absence of induction or vector
      integration in the vicinity of proto-oncogenes can diminish the advantages of the
      system. Here we investigated the effect of lentiviral transduction rate on tetP
      background activity, vector copy number (VCN), and clonal variability as a
      consequence of vector integration. We found an exponential relationship between
      VCN and gene transfer/expression level, accompanied by a linear relationship
      between VCN and tetP background activity. Long-term murine transplantation
      studies demonstrated stable and reversible transgene expression in serial
      recipients. Although analysis of associated clonal composition revealed
      development of clonal dominance in the presence and absence of induction, no
      indications of disease presented during the observation period. The majority of
      tetracycline-regulated vector integration sites were identified in intron/exons
      of metabolic/housekeeping and signaling genes or in noncoding/repeat regions of
      the genome. Furthermore, we demonstrated that the nature of the selected
      transgene might affect tetP background activity and inducibility in vivo.
      Limiting tetP-regulated gene transfer may avoid generation of clones with high
      VCN and enhanced tetP background activity. Our data help to establish physiologic
      and pathophysiologic systems to study dose-dependent mechanisms triggered by
      different levels of transgene expression in the context of basic HSC biology and
      cellular transformation models.

PMID- 24674754
TI  - Snail transcription factors in hematopoietic cell development: a model of
      functional redundancy.
AB  - Coordinated gene expression is crucial in facilitating proper lymphoid cell
      development and function. The precise patterns of gene expression during B- and T
      cell development are regulated through a complex interplay between a multitude of
      transcriptional regulators, both activators and repressors. We have recently
      identified the Snail family of transcription factors as playing significant and
      overlapping roles in lymphoid cell development, in that deletion of both SNAI2
      and SNAI3 was required to fully impact the generation of mature T and B cells.
      Analyses using compound heterozygote animals further demonstrated that SNAI2 and
      SNAI3 were partially haplosufficient and relatively equivalent in their ability
      to preserve B-cell generation in the bone marrow. In this review, we summarize
      studies elucidating the role of the Snail family in hematopoiesis, with a focus
      on lymphoid cell development. Using the Snail family as an example, we discuss
      the concepts of functional redundancy and strategies employed to assay
      transcription factor families for intramember compensation. 

PMID- 24674755
TI  - Perioperative blood transfusion is associated with worse clinical outcomes in
      resected lung cancer.
AB  - The deleterious effect of perioperative allogeneic blood transfusion in patients
      with resected lung cancer has been controversial. We conducted this meta-analysis
      to answer the question of whether perioperative allogeneic blood transfusion
      adversely affects recurrence and survival in patients with resected lung cancer.
      Included were 23 studies with 6,474 patients. The result showed allogeneic blood
      transfusion was significantly associated with earlier recurrence and worse
      survival in patients with surgically resected lung cancer. We suggest transfusion
      policy should be stricter in lung cancer patients undergoing resection,
      especially with early-stage disease. Prospective large-scale studies are still
      warranted. 

PMID- 24674756
TI  - PPM1B depletion induces premature senescence in human IMR-90 fibroblasts.
AB  - p53 and NF-kappaB are key transcription factors in regulating the gene expression
      program of cellular and organismal senescence. PPM1B is a member of the protein
      phosphatase 2C family and plays a role in negatively regulating p53 and NF-kappaB
      thereby possibly attenuating the gene expression program of cellular senescence.
      Here, possible involvement of PPM1B in replicative senescence has been
      investigated using the in vitro aging model of IMR-90 cells. PPM1B protein levels
      are progressively decreased in a replicative age-dependent manner. Importantly,
      PPM1B depletion induces a robust senescence phenotype as evidenced by significant
      growth arrest and senescence marker expression. Given that PPM1B depletion
      induced senescence is partially rescued by inactivating p38 MAPK, our results
      identify PPM1B as a critical regulator of both p38 MAPK-dependent and independent
      senescence pathways during normal cellular aging process. 

PMID- 24674757
TI  - Differential recruitment of executive resources during mind wandering.
AB  - Recent research has shown that mind wandering recruits executive resources away
      from the external task towards inner thoughts. No studies however have determined
      whether executive functions are drawn away in a unitary manner during mind
      wandering episodes, or whether there is variation in specific functions impacted.
      Accordingly, we examined whether mind wandering differentially modulates three
      core executive functions-response inhibition, updating of working memory, and
      mental set shifting. In three experiments, participants performed one of these
      three executive function tasks and reported their attentional state as either on
      task or mind wandering at random intervals. We found that mind wandering led to
      poorer performance in the response inhibition and working memory tasks, but not
      the set-shifting task. These findings suggest that mind wandering does not
      recruit executive functions in a monolithic manner. Rather, it appears to
      selectively engage certain executive functions, which may reflect the adaptive
      maintenance of ongoing task performance. 

PMID- 24674758
TI  - Unconscious processing modulates creative problem solving: evidence from an
      electrophysiological study.
AB  - Previous behavioral studies have identified the significant role of subliminal
      cues in creative problem solving. However, neural mechanisms of such unconscious
      processing remain poorly understood. Here we utilized an event-related potential
      (ERP) approach and sandwich mask technique to investigate cerebral activities
      underlying the unconscious processing of cues in creative problem solving.
      College students were instructed to solve divergent problems under three
      different conditions (conscious cue, unconscious cue and no-cue conditions). Our
      data showed that creative problem solving can benefit from unconscious cues,
      although not as much as from conscious cues. More importantly, we found that
      there are crucial ERP components associated with unconscious processing of cues
      in solving divergent problems. Similar to the processing of conscious cues,
      processing unconscious cues in problem solving involves the semantic activation
      of unconscious cues (N280-340) in the right inferior parietal lobule (BA 40), new
      association formation (P350-450) in the right parahippocampal gyrus (BA 36), and
      mental representation transformation (P500-760) in the right superior temporal
      gyrus (BA 22). The present results suggest that creative problem solving can be
      modulated by unconscious processing of enlightening information that is weakly
      diffused in the semantic network beyond our conscious awareness. 

PMID- 24674759
TI  - BMJ Awards 2014. Education team of the year: innovative approaches to support
      better care.

PMID- 24674760
TI  - Handheld ECG in analysis of arrhythmia and heart rate variability in children
      with Fontan circulation.
AB  - BACKGROUND: Our aim was to evaluate the intermittent use of a handheld ECG system
      for detecting silent arrhythmias and cardiac autonomic dysfunction in children
      with univentricular hearts. METHODS: Twenty-seven patients performed intermittent
      ECG recordings with handheld devices during a 14-day period. A manual arrhythmia
      analysis was performed. We analyzed heart rate variability (HRV) using scatter
      plots of all interbeat intervals (Poincare plots) from the total observation
      period. Reference values of HRV indices were determined from Holter-ECGs in 41
      healthy children. RESULTS: One asymptomatic patient had frequent ventricular
      extra systoles. Another patient had episodes with supraventricular tachycardia
      (with concomitant palpitations). Seven patients showed reduced HRV. CONCLUSIONS:
      Asymptomatic arrhythmia was detected in one patient. The proposed method for
      pooling of intermittent recordings from handheld or similar devices may be used
      for detection of arrhythmias as well as for cardiac autonomic dysfunction.

PMID- 24674761
TI  - What do the trace metal contents of urine and toenail samples from Qatar's farm
      workers bioindicate?
AB  - Qatar's farm workers provide a unique population for exposure study: they are
      young, healthy males. This study combined trace element profiles in urine and
      toenail with survey information from 239 farm workers to assess the extent to
      which the biomarkers provide complementary exposure information. Urinary Mo
      levels (average=114 ug/L) were elevated; average urinary values (ug/L) for all
      other elements were: V (1.02), Cr (0.55), Mn (2.15), Fe (34.1), Co (0.47), Ni
      (2.95), Cu (15.0), As (47.8), Se (25.7), Cd (1.09), Ba (22.5), Pb (2.50) and U
      (0.15). Average toenail concentrations (mg/kg) were: Mn (2.48), Cu (4.43), As
      (0.26), Se (0.58), Mo (0.07), Cd (0.03), Ba (1.00), Pb (0.51) and U (0.02). No
      significant association was found between corresponding elements in urine and
      toenails. Elemental profiles suggest groundwater (with the exception of Mo) and
      soil-dust-crop exposure pathways cannot account for elemental variations. The
      main factors moderating trace element contents are related to depuration
      processes involving participants' trace element body burden prior to work in
      Qatar, and interactions of trace element metabolic cycles which over-ride the
      exposure footprint. Toenail and urine need to be carefully validated before
      reliable use as biomarkers of exposure in general populations for most elements
      in the study.

PMID- 24674762
TI  - Prediction of the renal replacement therapy requirement in mechanically
      ventilated critically ill patients by combining biomarkers for glomerular
      filtration and tubular damage.
AB  - PURPOSE: Mechanically ventilated critically ill patients with high severity score
      indices need a very cautious therapeutic approach. Considering that inappropriate
      decisions on renal replacement therapy (RRT) initiation may promote unwanted
      adverse effects, we evaluated whether a panel of novel and traditional renal
      markers is superior to conventional renal marker in predicting RRT requirements
      in this group of patients. METHODS: This was a prospective observational study,
      performed at the two distinct multidisciplinary intensive care units (ICUs) of a
      1000-bed tertiary hospital. Of 310 consecutive patients, 106 patients fulfilled
      the inclusion criteria of the study. Urinary neutrophil gelatinase-associated
      lipocalin (uNGAL), serum creatinine (sCr) and serum cystatin C (sCysC) were
      determined on ICU admission. The predictive performance of all markers for first
      RRT was tested and compared based on the area under the receiver operating
      characteristic (ROC) curves. Time-dependent ROC curves were used to assess the
      earlier time point where the markers presented their maximum area under the curve
      (AUC). RESULTS: All studied biomarkers and acute physiology and chronic health
      evaluation (APACHE) II score, were significant independent predictors of RRT
      (uNGAL-AUC=0.73, sCysC-AUC=0.76, sCr-AUC=0.78, APACHE-AUC=0.73, P<0.0001). sCysC
      and sCr showed early maximum predictive ability within 10 days of ICU admission,
      while uNGAL and APACHE II score within 11 days of ICU admission. sCr combined
      with normalized (n)NGAL and sCysC combined with either nNGAL or uNGAL established
      best predictors for the RRT initiation (AUC-ROC=0.8). Distinguishing patients
      without acute kidney injury (AKI) on ICU entry, the combination of sCysC and
      APACHE II score proved best (AUC-ROC=0.78). CONCLUSIONS: Specific markers of
      kidney dysfunction and of kidney damage can be successfully combined to increase
      the prognostic capability for RRT initiation. The presence of AKI affects
      diagnostic performance. Without an established AKI on ICU admission, future RRT
      requirement was better predicted by the combination of illness severity with a
      marker of glomerular filtration rate. With AKI on ICU admission a combination of
      the marker of glomerular filtration rate with one of tubular injury proved best.

PMID- 24674763
TI  - Administration of proton pump inhibitors in critically ill medical patients is
      associated with increased risk of developing Clostridium difficile-associated
      diarrhea.
AB  - PURPOSE: Proton pump inhibitors (PPIs) effectively prevent gastrointestinal
      bleedings in critically ill patients at the intensive care unit (ICU). In non-ICU
      hospitalized patients, PPI administration increases the risk of infectious
      complications, especially Clostridium difficile-associated diarrhea (CDAD); but
      no such data are available for the ICU setting. MATERIALS AND METHODS: This is a
      retrospective, observational, single-center analysis (1999-2010) including 3286
      critically ill patients. RESULTS: A total of 91.3% of patients received stress
      ulcer prophylaxis by PPI (55.6%), histamine 2 receptor antagonists (5.8%),
      sucralfate (10.1%), or combinations (19.8%). Only 29 (0.9%) of 3286 patients
      developed gastrointestinal bleedings during the course of ICU treatment,
      independent from the type of prophylaxis. The PPIs were not an independent risk
      factor for nosocomial pneumonia. One hundred and ten (3.3%) patients developed
      CDAD during the course of ICU treatment, which was associated with prolonged ICU
      stay and increased ICU mortality (odds ratio, 1.59). Similar to fluoroquinolones
      and cephalosporins, PPI was identified as an independent risk factor (odds ratio,
      3.11) for developing CDAD at the ICU by multivariate analysis. CONCLUSIONS:
      Proton pump inhibitor therapy was an independent risk factor for CDAD in medical
      ICU patients. Instead of routine PPI use for bleeding prophylaxis, further trials
      should investigate risk-adjusted algorithms, balancing benefits, and threats of
      PPI medication.

PMID- 24674764
TI  - "Sometimes I walk and walk, hoping to get some peace." Dealing with hearing
      voices and sounds nobody else hears.
AB  - Our objective in this article is to add to the understanding of how people with
      mental illness experience dealing with hearing troublesome voices and sounds in
      everyday life. Fourteen people contributed through in-depth interviews and we
      analysed these using a hermeneutic phenomenological approach. We found that the
      participants (a) tried to block out the voices and sounds, (b) navigated the
      health care services, and (c) struggled to come to terms with limitations. Our
      overall understanding of how the participants dealt with hearing voices is that
      they sought to be independent and lead ordinary lives despite being troubled by
      voices. The participants fought desperately to find relief and avoid being
      overcome by the voices and sounds in intense phases. In less intense phases, they
      developed ways of getting along with daily life in spite of these experiences. We
      reflect on the implications of these findings and emphasize the need for care
      providers to attempt to understand and engage in collaborative explorations with
      service users in search of the most helpful ways of dealing with hearing
      troublesome voices and sounds in everyday life. 

PMID- 24674765
TI  - Non-alcoholic steatohepatitis weakens the acute phase response to endotoxin in
      rats.
AB  - BACKGROUND & AIMS: Patients with non-alcoholic steatohepatitis (NASH) have
      increased mortality, including from infections. We, therefore, tested in a rodent
      model of steatohepatitis whether the hepatic acute phase response is intact.
      METHODS: Steatohepatitis was induced in rats by feeding a high-fat, high
      cholesterol diet for 4 (early) and 16 weeks (advanced NASH). 2 h after low-dose
      LPS (0.5 mg/kg i.p.), we measured the serum concentrations of tumour necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6). We also measured liver mRNA's
      and the serum concentrations of acute phase proteins 24 h after LPS. RESULTS: Non
      alcoholic steatohepatitis in itself increased the liver mRNA levels of TNF-alpha
      and IL-6 and also the liver mRNA and serum levels of the acute phase proteins.
      The exposure to LPS increased serum TNF-alpha in both early and advanced NASH and
      more so than in the control rats. However, the increases in acute phase protein
      genes in liver tissue and proteins in the blood were lower than in the control
      rats. CONCLUSION: In rats with early or advanced experimental NASH, LPS despite
      an increased interleukin release resulted in a blunted acute phase protein
      response. This tachyphylaxis may be part of the mechanism for the increased
      infection susceptibility of patients with NASH. We speculate that the steatosis
      related interleukin release desensitises the signalling pathway leading to acute
      phase protein synthesis.

PMID- 24674766
TI  - To disclose or not: does a decision tool help?

PMID- 24674767
TI  - Lambertellin system, the mechanism for fungal replacement of Monilinia fructigena
      with Lambertella corni-maris without competitive inhibition on agar media.
AB  - The 'Lambertellin system' was disclosed which rationally explains the fungal
      replacement (mycoparasitism) of Monilinia fructigena (M. f., the host) with
      Lambertella corni-maris (L. corni-maris, the parasite) without competitive
      inhibition in the simultaneous incubations on agar media. The 'Lambertellin
      system' involves; (a) L. corni-maris secretes nontoxic lambertellols (1, 2) as
      the diffusible precursors of the authentic responsible substance 3 regardless of
      existence of the host M. f.; (b) In the absence of the host, the environment
      around the parasite is kept under neutral condition, and both 1 and 2 are readily
      transformed into 3; (c) Lambertellin (3) inhibits not only the host but also the
      parasite. The parasite degrades 3 for detoxification; and (d) Upon the host M. f.
      approaching closely to the area where the parasite inhabits, the environment
      around the parasite becomes acidic to stabilize 1 and 2, which gives them a
      chance to diffuse into the host area. Then these are gradually transformed into 3
      to inhibit the host without damaging the parasite. This mechanism also accords
      with the progress of 'Natsu-Nenju' disease on apple fruits, which is known to be
      a mysterious phyto-disease because of two unique stages of its lifecycle,
      anamorphic (asexual) and teleomorphic (sexual). The 'Lambertellin system' would
      be categorized as a novel class of alleropathies. 

PMID- 24674768
TI  - Soya and isoflavone intakes associated with reduced risk of oesophageal cancer in
      north-west China.
AB  - OBJECTIVE: To ascertain the association between soya consumption, isoflavone
      intakes and oesophageal cancer risk in remote north-west China, where the
      incidence of oesophageal cancer is known to be high. DESIGN: Case-control study.
      Information on habitual consumption of soya foods and soya milk was obtained by
      personal interview. The intakes of isoflavones were then estimated using the US
      Department of Agriculture nutrient database. Logistic regression analyses were
      performed to assess the association between soya consumption, isoflavone intakes
      and oesophageal cancer risk. SETTING: Urumqi and Shihezi, Xinjiang Uyghur
      Autonomous Region, China. SUBJECTS: Participants were 359 incident oesophageal
      cancer patients and 380 hospital-based controls. RESULTS: The oesophageal cancer
      patients consumed significantly less (P < 0.001) total soya foods (mean 57.2 (sd
      119.0) g/d) and soya milk (mean 18.8 (sd 51.7) ml/d) than the controls (mean 93.3
      (sd 121.5) g/d and mean 35.7 (sd 73.0) ml/d). Logistic regression analyses showed
      an inverse association between intake of soya products and the risk of
      oesophageal cancer. The adjusted odds were OR = 0.33 (95 % CI 0.22, 0.49) and OR
      = 0.48 (95 % CI 0.31, 0.74) for consuming at least 97 g of soya foods and 60 ml
      of soya milk daily (the highest tertiles of consumption), respectively, relative
      to the lowest tertiles of consumption. Similarly, inverse associations with
      apparent dose-response relationships were found between isoflavone intakes and
      oesophageal cancer risk. CONCLUSIONS: Habitual consumption of soya products
      appears to be associated with reduced risk of oesophageal cancer in north-west
      China.

PMID- 24674769
TI  - Lack of reproducibility in re-evaluating associations between GCH1 polymorphisms
      and Parkinson's disease and isolated dystonia in an Australian case--control
      group.

PMID- 24674770
TI  - Daytime sleep in Parkinson's disease measured by episodes of immobility.
AB  - Excessive daytime sleepiness (EDS) is common in Parkinson's Disease (PD).
      Actigraphy uses periods of immobility as surrogate markers of nighttime sleep but
      there are no examples of its use in assessing EDS of PD. A commercial wrist worn
      system for measuring bradykinesia and dyskinesia also detects 2 min periods of
      immobility, which have a 85.2% concordance with the detection of sleep by
      ambulatory daytime polysomnography, (p < 0.0001 Chi Squared). High Epworth
      Sleepiness Scores (ESS) were associated with a proportion of time immobile (PTI)
      (p = 0.01 Mann-Whitney U). The median PTI between 0900 and 1800 h w in 30 age
      matched control subjects was 2%, representing 10 min and PTI at or above the 75th
      percentile (5% or 27 min) was taken as a high level. PD patients had higher PTI
      (median 4.8%) than controls (p < 0.0001, Mann-Whitney U). PD subjects with a high
      PTI had more bradykinesia, less dyskinesia and higher PDQ39 scores than those
      with low PTI. There was no relationship between PTI and dose or type of PD
      medications. However, in 53% of subjects, PTI increased in the 30-60 min after
      levodopa confirming that in some subjects levodopa results in increased
      sleepiness. In summary, immobility is a surrogate marker of daytime sleep in PD,
      confirmed by correlation with PSG and ESS. PD subjects measured this way are more
      likely to be sleepy and sleepy PD subjects are more likely to be bradykinetic and
      have a higher PDQ39. Levodopa leads to an increase in sleepiness in more than
      half of subjects post dosing. 

PMID- 24674771
TI  - Endothelin-1-induced priming to capsaicin in young animals.
AB  - Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization
      in humans and spontaneous nociceptive behaviors when injected into the periphery
      in rats. This study sought to examine the effect of ET-1 exposure in the neonatal
      period on subsequent contralateral capsaicin-induced secondary mechanical
      hyperalgesia. ET-1 or saline was injected into the left plantar hindpaw on
      postnatal day 7 (P7). On postnatal day 11 (P11), capsaicin cream or control
      lotion was applied to the right dorsum hind paw and mechanical paw withdrawal
      thresholds were measured in the plantar hind paw. In saline control males, P11
      administration of capsaicin produced a secondary mechanical hyperalgesia that was
      still present at 2h. Neonatal priming with ET-1 did not alter the magnitude or
      the duration of secondary mechanical hyperalgesia in males. In contrast, in
      control females, P11 administration of capsaicin produced less than 40 min of
      mechanical hyperalgesia. Neonatal priming with ET-1 prolonged the duration of
      secondary mechanical hyperalgesia in females. Priming with ET-1 on P7 led to a
      significant increase in capsaicin-induced Fos expression in the dorsal horn of
      the spinal cord in both males and females compared to controls (p<0.001). These
      findings further suggest that pain in early life may alter future responses to
      painful stimuli at both the behavioral and neuronal level.

PMID- 24674772
TI  - Involvement of amygdaloid neuropeptide Y in the anxiolytic effects of acupuncture
      during ethanol withdrawal in rats.
AB  - The role of neuropeptide Y (NPY) in the central nucleus of amygdala (CeA) in the
      preventive effects of acupuncture against ethanol withdrawal-induced anxiety was
      investigated. Rats were treated with 3g/kg/day of ethanol for 28 days, followed
      by 3 days of withdrawal. Bilateral acupuncture treatment at HT7 (Shen-Men), PC6
      (Nei-Guan) or a non-acupoint was respectively added to the rats during the
      withdrawal once a day for three days. Enzyme-linked immunosorbent assays and real
      time polymerase chain reaction analyses showed there was a significant decrease
      in NPY protein and mRNA expression in the CeA during ethanol withdrawal, which
      was reversed by acupuncture at HT7 but neither at PC6 nor at a non-acupoint.
      Acupuncture at HT7 also greatly inhibited the decrease in cAMP response element
      binding protein (CREB) phosphorylation in the CeA. In elevated plus maze tests, a
      selective NPY Y1 receptor antagonist BIBP 3226 into the CeA before the
      acupuncture abolished almost completely the anxiolytic effect of acupuncture at
      HT7. These results suggest that acupuncture at HT7 rescues the depletion of
      amygdaloid NPY and reverses the decrease in CREB phosphorylation to produce
      anxiolytic effects during ethanol withdrawal. 

PMID- 24674775
TI  - Schizophrenia and bipolar disorder show both common and distinct changes in
      cortical interneuron markers.
AB  - Schizophrenia and bipolar disorder are often viewed as distinct clinical
      disorders, however there is substantial overlap in their neuropathologies. While
      compromised cortical interneurons are implicated in both diseases, few studies
      have examined the relative contribution of the distinct interneuron populations
      to each psychotic disorder. We report reductions in somatostatin and vasoactive
      intestinal peptide mRNAs in prefrontal and orbitofrontal cortices in bipolar
      disorder (n=31) and schizophrenia (n=35) compared to controls (n=34) and
      increased calbindin mRNA in schizophrenia. We show, at the molecular level,
      shared deficits in interneuron markers in schizophrenia and bipolar disorder, and
      a unique interneuron marker increase in schizophrenia. 

PMID- 24674773
TI  - Intracellular sequestration of zinc, cadmium and silver in Hebeloma mesophaeum
      and characterization of its metallothionein genes.
AB  - Sequestration of intracellular heavy metals in eukaryotes involves
      compartmentalization and binding with cytosolic, cysteine-rich metallothionein
      (MT) peptides. We examined the roles of these processes in handling of zinc (Zn),
      cadmium (Cd) and silver (Ag) in sporocarps and a metal-exposed extraradical
      mycelium of Hebeloma mesophaeum, the Zn-accumulating ectomycorrhizal (EM) species
      frequently associated with metal disturbed sites. Size exclusion chromatography
      revealed that the majority of Zn and Cd in the sporocarps and mycelium was
      contained in a low molecular mass fraction attributable to compartmentalized
      metal. The staining of hyphal cells with the Zn-specific Zinquin and Cd-specific
      Leadmium fluorescent tracers labeled Zn and Cd in small, punctuated vesicles and
      vacuoles, respectively. By contrast, the sporocarp and mycelium Ag was associated
      with cysteine-rich, 5-kDa peptides. The peptides of the same size were also
      identified in minor Zn and Cd complexes from the metal-exposed mycelium. We have
      further isolated and characterized HmMT1, HmMT2 and HmMT3 genes coding for
      different 5-kDa MTs of H. mesophaeum collected at a lead smelter site.
      Heterologous complementation assays in metal-sensitive yeast mutants indicated
      that HmMTs encode functional, metal-specific peptides: only HmMT1 was able to
      complement sensitivity to Zn; HmMT1 conferred higher tolerance to Cd and Cu than
      HmMT2 or HmMT3; and both HmMT2 and HmMT3, but not HmMT1, conferred increased
      tolerance to Ag. The presence of HmMT1 and HmMT3, but not HmMT2, was also
      confirmed in a H. mesophaeum isolate from an unpolluted site. Gene expression
      analysis in the extraradical mycelium of this isolate revealed that the
      transcription of HmMT1 was preferentially induced in the presence of Zn and Cd,
      while Ag was a stronger inducer of HmMT3. Altogether, these results improve our
      understanding of the handling of intracellular Zn, Cd and Ag in Hebeloma and
      represent the first evidence suggesting involvement of MTs in sequestration of Zn
      in EM fungi. 

PMID- 24674777
TI  - Luminal ATP: the missing link between intestinal alkaline phosphatase, the gut
      microbiota, and inflammation?

PMID- 24674776
TI  - Upregulation of KCa3.1 K(+) channel in mesenteric lymph node CD4(+) T lymphocytes
      from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease.
AB  - The intermediate-conductance Ca(2+)-activated K(+) channel KCa3.1/KCNN4 plays an
      important role in the modulation of Ca(2+) signaling through the control of the
      membrane potential in T lymphocytes. Here, we study the involvement of KCa3.1 in
      the enlargement of the mesenteric lymph nodes (MLNs) in a mouse model of
      inflammatory bowel disease (IBD). The mouse model of IBD was prepared by exposing
      male C57BL/6J mice to 5% dextran sulfate sodium for 7 days. Inflammation-induced
      changes in KCa3.1 activity and the expressions of KCa3.1 and its regulators in
      MLN CD4(+) T lymphocytes were monitored by real-time PCR, Western blot, voltage
      sensitive dye imaging, patch-clamp, and flow cytometric analyses. Concomitant
      with an upregulation of KCa3.1a and nucleoside diphosphate kinase B (NDPK-B), a
      positive KCa3.1 regulator, an increase in KCa3.1 activity was observed in MLN
      CD4(+) T lymphocytes in the IBD model. Pharmacological blockade of KCa3.1
      elicited the following results: 1) a significant decrease in IBD disease
      severity, as assessed by diarrhea, visible fecal blood, inflammation, and crypt
      damage of the colon and MLN enlargement compared with control mice, and 2) the
      restoration of the expression levels of KCa3.1a, NDPK-B, and Th1 cytokines in IBD
      model MLN CD4(+) T lymphocytes. These findings suggest that the increase in
      KCa3.1 activity induced by the upregulation of KCa3.1a and NDPK-B may be involved
      in the pathogenesis of IBD by mediating the enhancement of the proliferative
      response in MLN CD4(+) T lymphocyte and, therefore, that the pharmacological
      blockade of KCa3.1 may decrease the risk of IBD.

PMID- 24674778
TI  - [Can I continue to use platelet-rich-plasma on my patients? How do I use it
      legally?].

PMID- 24674779
TI  - Changes in B and T-cell subsets and NMO-IgG levels after immunoglobulins and
      rituximab treatment for an acute attack of neuromyelitis optica.
AB  - BACKGROUND: There is increasing evidence supporting that neuromyelitis optica
      (NMO) is an inflammatory humoral mediated disorder associated with NMO-IgG/AQP-4
      antibodies. However, little is known about the subsets of B cells and T cells
      that contribute to the pathogenesis or therapy response. OBJECTIVES: To describe
      the clinical and immunological changes associated with intravenous
      immunoglobulins (IV-Igs) plus rituximab (RTX) in a patient with a severe acute
      attack of NMO and intrathecal synthesis of NMO-IgG/AQP-4, who previously did not
      respond to intravenous methylprednisolone and plasma exchange. METHODS: We
      sequentially analysed the levels of NMO-IgG/AQP-4 by immunohistochemistry, and B
      and T cells subsets by multiparametric flow-cytometry, in the CSF and peripheral
      blood (PB), before and alter IV-Igs plus RTX therapy. RESULTS: In the CSF before
      treatment, and compared with PB, there was a higher percentage of CD4(+) T cells
      and a lower percentage of CD8(+) T cells and CD19(+) B cells. After therapy, the
      percentage of CD4(+) T cells remained high, and that of CD8(+) T cells increased.
      The observed decrease in the percentage of CD19(+) B cells was lower than in the
      PB. When the CSF was compared, it was found that the percentage of effector
      memory and effector CD8(+) T cells had increased after therapy, and that of IgM
      memory B cells and switched-memory B cells decreased. The observed changes
      paralleled the decrease of NMO-IgG/AQP-4 results to negative and the clinical
      improvement. CONCLUSIONS: Our findings confirm that, besides intrathecal humoral
      immune response against AQP4, B and T cell subsets are involved in the modulation
      of inflammation within and outside the central nervous system.

PMID- 24674780
TI  - Subconjunctival hemorrhage after high frequency right-sided repetitive
      transcranial magnetic stimulation.

PMID- 24674781
TI  - rTMS for treatment of depression in a patient with cerebral amyloid angiopathy: a
      case report on safety and efficacy.

PMID- 24674782
TI  - Evaluation of four steering wheels to determine driver hand placement in a static
      environment.
AB  - While much research exists on occupant packaging both proprietary and in the
      literature, more detailed research regarding user preferences for subjective
      ratings of steering wheel designs is sparse in published literature. This study
      aimed to explore the driver interactions with production steering wheels in four
      vehicles by using anthropometric data, driver hand placement, and driver grip
      design preferences for Generation-Y and Baby Boomers. In this study, participants
      selected their preferred grip diameter, responded to a series of questions about
      the steering wheel grip as they sat in four vehicles, and rank ordered their
      preferred grip design. Thirty-two male participants (16 Baby Boomers between ages
      47 and 65 and 16 Generation-Y between ages 18 and 29) participated in the study.
      Drivers demonstrated different gripping behavior between vehicles and between
      groups. Recommendations for future work in steering wheel grip design and
      naturalistic driver hand positioning are discussed. 

PMID- 24674783
TI  - Dynamical structure of alphaB-crystallin.
AB  - The human small heat-shock protein alphaB-crystallin is an extremely difficult
      molecule to study, with its inherent structural dynamics posing unique challenges
      to all biophysical and structural biology techniques. Here we highlight how the
      polydispersity and quaternary dynamics of alphaB-crystallin are intrinsically
      inter-twined, and how this can impact on measurements of the oligomeric
      distribution. We show that, in spite of these difficulties, considerable
      understanding of the varied fluctuations alphaB-crystallin undergoes at
      equilibrium has emerged in the last few years. By reporting on data obtained from
      a variety of biophysical techniques, we demonstrate how the alphaB-crystallin
      solution ensemble is governed by molecular motions of varying amplitude and time
      scales spanning several orders of magnitude. We describe how these diverse
      measurements are being used to construct an integrated view of the dynamical
      structure of alphaB-crystallin, and highlight areas that require further
      interrogation. With its study motivating the refinement of experimental
      techniques, and the development of new approaches to combine the hybrid datasets,
      we conclude that alphaB-crystallin continues to represent a paradigm for
      dynamical biology. 

PMID- 24674784
TI  - Metronomic oral cyclophosphamide chemotherapy possibly contributes to
      stabilization of disease in patients with metastatic castration-resistant
      prostate cancer: a prospective analysis of consecutive cases.
AB  - INTRODUCTION/BACKGROUND: Castration-resistant prostate cancer remains a
      therapeutic challenge, even after establishing the survival benefits of docetaxel
      chemotherapy. Metronomic chemotherapy stabilizes various cancers through
      antiangiogenic and immunomodulatory effects. We evaluate the activity of
      metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and
      assess predictive factors for clinical outcomes. PATIENTS AND METHODS: Twenty
      four patients with metastatic CRPC received an oral cyclophosphamide and
      dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and
      resistant to previous docetaxel chemotherapy. Six patients had refused to receive
      docetaxel chemotherapy, and 7 patients could not receive the therapy because of
      deteriorated performance status. All patients had already shown resistance to
      continuous dexamethasone therapy. Demographic and clinical data were collected
      prospectively. RESULTS: A total of 16 patients (66.7%) experienced a reduction in
      PSA levels, and PSA decrease >= 50% was observed in 8 patients (33.3%). The
      median PSA progression-free and overall survival were 5.0 months and 19.0 months,
      respectively. The favorable PSA decrease had no associations with the progression
      free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8
      months achieved long overall survival of 28 months in median. None of the
      patients discontinued therapy because of the presence of toxicities. CONCLUSION:
      Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can
      be an option for metastatic CRPC patients. The benefit of this regimen could not
      always be evaluated according to a favorable PSA decrease; thus, we must identify
      the predictive factors of response other than known clinical factors.

PMID- 24674786
TI  - Our pursuit of excellence.

PMID- 24674785
TI  - Positive FDG-PET/CT scans of a residual seminoma after chemotherapy and
      radiotherapy: case report and review of the literature.

PMID- 24674787
TI  - Crisis considerations for the perioperative setting.

PMID- 24674788
TI  - Author response.

PMID- 24674789
TI  - Missing perspective in the discussion of safety culture.

PMID- 24674790
TI  - Patients are unlikely to use a patient's checklist.

PMID- 24674791
TI  - The challenge of physician-nurse communication.

PMID- 24674792
TI  - Author response.

PMID- 24674793
TI  - Understanding medication compounding issues.
AB  - The potential for contamination of compounded products and the resulting
      infections are a serious threat to patient safety. Immediate use products are
      used frequently in the perioperative department, and perioperative nurses should
      be familiar with the guidelines and practices that aim to reduce the
      contamination that can occur during the sterile compounding process. Four common
      themes lead to successful compounding: quality (eg, product identification,
      purity, stability, compatibility, risk level assessment), the environment (eg,
      using a segregated compounding area with specialized airflow capabilities,
      reducing particulate matter, practicing proper hand hygiene, performing gloved
      fingertip sampling, properly cleaning equipment and work areas), personnel
      activities (eg, familiarity with types of containers used and how often they can
      be accessed, following expiration dates and the number of times containers can be
      accessed), and the control process (eg, process monitoring, quality improvement).
      If a third-party vendor is contracted to handle compounding for a facility,
      perioperative personnel should be aware of the responsibilities for the facility
      and the vendor to ensure a quality compounding program. 

PMID- 24674794
TI  - Identifying pediatric emergence delirium by using the PAED Scale: a quality
      improvement project.
AB  - Pediatric emergence delirium is a postoperative phenomenon characterized by
      aberrant cognitive and psychomotor behavior, which can place the patient and
      health care personnel at risk for injury. A common tool for identifying emergence
      delirium is the Level of Consciousness-Richmond Agitation and Sedation Scale (LOC
      RASS), although it has not been validated for use in the pediatric population.
      The Pediatric Anesthesia Emergence Delirium Scale (PAED) is a newly validated
      tool to measure emergence delirium in children. We chose to implement and
      evaluate the effectiveness and fidelity of using the PAED Scale to identify
      pediatric emergence delirium in one eight-bed postanesthesia care unit in
      comparison with the traditional LOC-RASS. The overall incidence of pediatric
      emergence delirium found by using the LOC-RASS with a retrospective chart review
      (3%) was significantly lower than the incidence found by using the LOC-RASS
      (7.5%) and PAED Scale (11.5%) during the implementation period. Our findings
      suggest that the PAED Scale may be a more sensitive measure of pediatric
      emergence delirium, and, in the future, we recommend that health care personnel
      at our facility use the PAED Scale rather than the LOC-RASS. 

PMID- 24674795
TI  - Implementing AORN recommended practices for selection and use of packaging
      systems for sterilization.
AB  - The delivery of sterile products to the sterile field is essential to
      perioperative practice. The use of protective packaging for sterilized items is
      crucial to helping ensure that patients receive sterile items for surgical
      procedures. AORN's "Recommended practices for selection and use of packaging
      systems for sterilization" offers guidance to perioperative team members in
      evaluating, selecting, and using packaging systems that permit sterilization of
      the contents, prevent contamination of sterilized items until the package is
      opened for use, protect the items from damage during transport and storage, and
      permit aseptic delivery of the items to the sterile field. 

PMID- 24674796
TI  - Crisis management of a hemorrhagic emergency in the OR.

PMID- 24674797
TI  - The growing role of patient engagement: relationship-based care in a changing
      health care system.

PMID- 24674798
TI  - Transforming the health care environment collaborative.

PMID- 24674800
TI  - Undetected foreign object.

PMID- 24674801
TI  - A direct technique to fabricate an intraoral shield for unilateral head and neck
      radiation.
AB  - A radiation oncologist may ask the prosthodontist to fabricate an intraoral
      shield when ipsilateral fields are used for patients with head and neck cancer. A
      technique for its fabrication is described that can be accomplished with
      materials and equipment that are readily available in the dental office.
      Baseplate wax is used intraorally to fabricate a pattern, which is duplicated
      with irreversible hydrocolloid material. Autopolymerizing acrylic resin is then
      used to make the shield. This simple technique can be completed in a single
      visit. 

PMID- 24674802
TI  - Clinical outcomes of lithium disilicate single crowns and partial fixed dental
      prostheses: a systematic review.
AB  - STATEMENT OF PROBLEM: Lithium disilicate is a relatively new and popular
      restorative material for esthetic and functional rehabilitations, but the
      evidence for clinical outcomes is not clear. PURPOSE: The purpose of this
      systematic review was to analyze the short-term (1- to 5-year) and medium-term (5
      to 10-year) survival rates of lithium disilicate single crowns and partial fixed
      dental prostheses. MATERIAL AND METHODS: An electronic search for articles in the
      English-language literature published between January 1998 and June 2013 was
      performed with the PubMed search engine. The specific search terms used were
      lithium disilicate, lithium silicate, IPS e max, IPS Empress, CAD CAM, pressed
      ceramic, monolithic, and bilayer. After applying predetermined inclusion and
      exclusion criteria, the definitive list of selected articles was suitable only
      for calculating the interval survival rate and cumulative survival rate. RESULTS:
      The electronic search resulted in 2033 titles. The systematic application of
      inclusion and exclusion criteria resulted in 12 clinical studies that addressed
      the clinical outcomes of lithium disilicate restorations. Of these, 2 were
      randomized controlled trials, 5 were prospective studies, 1 was a retrospective
      study, and 4 studies were descriptive in nature. All 12 studies reported on tooth
      retained lithium disilicate restorations. The 2-year cumulative survival rate for
      single crowns was 100%, and the 5-year cumulative survival rate was 97.8%. The 2
      year cumulative survival rate for fixed dental prostheses was 83.3%, and the 5
      year cumulative survival rate was 78.1%. The cumulative survival rate over a 10
      year period, primarily owing to data from 1 study, was 96.7% for single crowns
      and 70.9% for fixed dental prostheses. CONCLUSIONS: For lithium disilicate single
      crowns, the existing evidence indicates excellent short-term survival rates, but
      the evidence for medium-term survival is limited. For lithium disilicate fixed
      dental prostheses, the evidence for short-term survival is fair, although
      limited, but the evidence for medium-term survival is not promising. The majority
      of failures in both types of restorations were reported in the posterior region.

PMID- 24674803
TI  - Interface toughness of a zirconia-veneer system and the effect of a liner
      application.
AB  - STATEMENT OF PROBLEM: Chipping of veneering porcelain and delamination of a
      zirconia-veneer interface are 2 common clinical failure modes for zirconia-based
      restorations and may be partially due to weak interface bonding. The effect of
      liner on the bond strength of the interface has not been clearly identified.
      PURPOSE: The purpose of the research was to evaluate the interface toughness
      between the zirconia core and veneering porcelain by means of a fracture
      mechanics test and to assess the effect of liner on the bond strength of the
      interface. MATERIAL AND METHODS: Thirty bilayered beam-shape specimens were
      prepared and divided into 2 groups according to liner application. The specimens
      in each group were subdivided into 3 subgroups in accordance with 3 different
      veneer thicknesses. A fracture mechanics test was used on each specimen, and the
      energy release rate, G, and phase angle, psi, were calculated according to the
      experimental results. A video microscope was used to monitor the crack
      propagation, and a scanning electron microscope was used to identify the fracture
      mode after testing. Two-way ANOVA and the Tukey honestly significant difference
      test were performed to analyze the experimental data (alpha=.05) . RESULTS: At
      each phase angle, the interfaces without a liner had higher mean G values than
      the interfaces with a liner. Both of the interfaces showed mixed failure mode
      with thin layers of a veneer or a liner that remained on the zirconia surfaces.
      CONCLUSIONS: Liner application before veneering reduced the interface toughness
      between zirconia and veneer.

PMID- 24674804
TI  - Evaluation of a modular palatal lift prosthesis with a silicone velar lamina for
      hypernasal patients.
AB  - STATEMENT OF PROBLEM: Speech bulbs and palatal lift prostheses are used to
      improve oral-nasal balance in speakers with hypernasality resulting from
      velopharyngeal dysfunction. Fabricating such speech prostheses is often a
      protracted process, and the nasopharyngeal impression can be uncomfortable for
      the client. PURPOSE: The purpose of this study was to develop and test a modular
      palatal lift prosthesis with a silicone velar lamina that can be fabricated
      without a nasopharyngeal impression. MATERIAL AND METHODS: Six adult participants
      with different etiologies were treated with both a conventional palatal lift
      prosthesis and the new prosthesis. The outcome measures were nasalance scores,
      speech acceptability ratings, and participant responses on a questionnaire.
      Inferential statistical analyses were conducted with nonparametric Friedman tests
      and 2-tailed paired Wilcoxon signed ranks tests. The probability was set at P<.1.
      RESULTS: Among the 3 speaking conditions (no prosthesis, acrylic resin
      prosthesis, modular silicone palatal lift prosthesis), no differences were found
      in nasalance scores for the oral stimuli. For the nasal sentences, a numerically
      greater reduction was observed for the silicone than for the acrylic resin
      prosthesis. Speech acceptability was better with the modular silicone palatal
      lift prosthesis (z=2.032, P<.05) and the acrylic resin prosthesis (z=1.753, P<.1)
      than with no prosthesis. The questionnaire showed better subjective speech
      acceptability with the acrylic resin prosthesis (z=1.706, P<.05) and the modular
      silicone palatal lift prosthesis (z=1.706, P<.05) than with no prosthesis.
      Swallowing comfort was also numerically better for the acrylic resin prosthesis
      than for the modular silicone palatal lift prosthesis. CONCLUSIONS: This study
      demonstrates the feasibility of a new design for a flexible and modular palatal
      lift prosthesis. The functional outcomes were comparable to those of the
      traditional design. Although the overall results in this study favored the
      traditional prosthesis, the new design may be viable for patients who require
      alternative treatment solutions.

PMID- 24674805
TI  - Presurgical management of unilateral cleft lip and palate in a neonate: a
      clinical report.
AB  - A cleft lip and palate consists of fissures of the upper lip and/or palate, and
      is the most commonly seen orofacial anomaly that involves the middle third of the
      face. Early treatment of patients with a cleft lip and palate is important
      because of esthetic, functional, and psychological concerns. Nasoalveolar molding
      provides excellent results when started immediately after birth. This clinical
      report describes the presurgical management of an infant with a complete
      unilateral cleft of the soft palate, hard palate, alveolar ridge, and lip. 

PMID- 24674806
TI  - Complete mouth reconstruction with implant-supported fixed partial dental
      prostheses fabricated with zirconia frameworks: a 4-year clinical follow-up.
AB  - Few scientific reports regarding the success of complete mouth partial fixed
      dental prostheses frameworks fabricated with zirconia are available, especially
      when dental implants serve as the abutments. A complete mouth reconstruction with
      zirconia frameworks veneered with feldspathic porcelain is reported involving a
      65-year-old white woman who presented with partial edentulism and an unrestorable
      remaining dentition. After examination, 14 implants were planned (8 in the
      maxillary arch and 6 in the mandibular arch), and implant-supported zirconia
      framework screw-retained partial fixed dental prostheses (ISZPFDPs) were
      fabricated and made in sections for easier retrievability and management. No
      major complications were encountered during follow-up appointments at 6-month
      intervals for 4 years. However, minor fractures of the veneering ceramic were
      noted 4 years after placement. The ISZPFDPs were well accepted by the patient and
      had a favorable outcome in terms of patient acceptability and success, despite
      some complications. 

PMID- 24674807
TI  - Complete mouth implant rehabilitation with a zirconia ceramic system: a clinical
      report.
AB  - Currently available ceramic systems offer a wide array of prosthetic advantages,
      including superior esthetics and enhanced physical and mechanical properties. The
      dental ceramic with the highest reported mechanical properties is zirconia. This
      clinical report describes a complete mouth implant rehabilitation with computer
      aided design/computer-aided manufacturing technology and monolithic zirconia. 

PMID- 24674808
TI  - Coordinate geometry method for capturing and evaluating crown preparation
      geometry.
AB  - STATEMENT OF PROBLEM: A validated universal method requiring no human input is
      needed to capture and evaluate preparation geometries in a manner that can be
      used to see the correlation of different parameters. PURPOSE: The purpose of this
      study was to present a method of capturing and evaluating crown preparation
      geometry. MATERIAL AND METHODS: One manually machined acrylic resin block and 9
      randomly selected preparations for ceramic complete crowns prepared by general
      dentists were selected and prepared. The specimens were scanned (3D scanner;
      Nobel Biocare), and buccolingual and mesiodistal cross section images were
      collected. The images were imported into digitizing software (Engauge Digitizer
      4.1) to convert the outlines into x and y coordinates. Six points were chosen by
      using a set of algorithms, and the resulting parameters were calculated. RESULTS:
      The acrylic resin block was milled with a 12 degree total occlusal convergence
      (TOC) instrument producing a 12.83 degree TOC. For the other specimens, average
      TOC values ranged from 18 degrees to 52 degrees. The mean average margin width
      was 0.70 mm, and the mean average base dimension was 6.23 mm. The surface
      area/volume ratio, resistance length, and limiting taper were also calculated.
      CONCLUSIONS: The method described provides a basis for accurately evaluating
      preparation geometry without human input.

PMID- 24674809
TI  - Marginal adaptation of four inlay casting waxes on stone, titanium, and zirconia
      dies.
AB  - STATEMENT OF PROBLEM: Different inlay casting waxes do not produce copings with
      satisfactory marginal accuracy when used on different die materials. PURPOSE: The
      purpose of this study was to evaluate the marginal accuracy of 4 inlay casting
      waxes on stone dies and titanium and zirconia abutments and to correlate the
      findings with the degree of wetting between the die specimens and the inlay
      casting waxes. MATERIAL AND METHODS: The inlay casting waxes tested were Starwax
      (Dentaurum), Unterziehwachs (Bredent), SU Esthetic wax (Schuler), and Sculpturing
      wax (Renfert). The marginal opening of the waxes was measured with a
      stereomicroscope on high-strength stone dies and on titanium and zirconia
      abutments. Photographic images were obtained, and the mean marginal opening for
      each specimen was calculated. A total of 1440 measurements were made. Wetting
      between die materials and waxes was determined after fabricating stone, titanium,
      and zirconia rectangular specimens. A calibrated pipette was used to place a drop
      of molten wax onto each specimen. The contact angle was calculated with software
      after an image of each specimen had been made with a digital camera. Collected
      data were subjected to a 2-way analysis of variance (alpha=.05). Any association
      between marginal accuracy and wetting of different materials was found by using
      the Pearson correlation. RESULTS: The wax factor had a statistically significant
      effect both on the marginal discrepancy (F=158.31, P<.001) and contact angle
      values (F=68.09, P<.001). A statistically significant effect of the die material
      factor both on the marginal adaptation (F=503.47, P<.001) and contact angle
      values (F=585.02, P<.001) was detected. A significant correlation between the
      marginal accuracy and the contact angle values (Pearson=0.881, P=.01) was also
      found. CONCLUSIONS: Stone dies provided wax copings with the best marginal
      integrity, followed by titanium and zirconia abutments. Unterziehwachs (Bredent),
      wax produced the best marginal adaptation on different die materials. A
      significant correlation was found between the marginal accuracy and the contact
      angle values. As the contact angle value became smaller, the marginal accuracy
      improved. All combinations of waxes and stone and titanium dies presented a high
      wettability.

PMID- 24674810
TI  - Adhesion of dental porcelain to cast, milled, and laser-sintered cobalt-chromium
      alloys: shear bond strength and sensitivity to thermocycling.
AB  - STATEMENT OF PROBLEM: New technologies have led to the introduction of new
      materials, so an evaluation of the adhesion of ceramics to these materials is
      needed. PURPOSE: The purpose of this study was to compare the shear bond strength
      of dental porcelain to cast, milled, and laser-sintered cobalt-chromium alloys,
      and to investigate the adhesive bond and failure type after thermocycling, 90
      metal cylinders (10 mm diameter and 10 mm height) were prepared from cast (30
      specimens), milled (30 specimens), and laser-sintered (30 specimens) alloys.
      MATERIAL AND METHODS: Ceramic cylinders (2.5 mm diameter and 4 mm length) were
      fused to the alloy cylinders. For each group, 15 specimens were thermocycled 5500
      times at temperatures between 4 degrees C and 60 degrees C before testing. After
      testing, the specimen surfaces were visually examined to determine the failure
      mode. Differences in adhesion values according to manufacturing method, testing
      condition (thermocycling or no thermocycling), and interaction between the
      factors were evaluated with a 2-way ANOVA. The chi(2) test (95% confidence level)
      was performed to determine whether the failure mode was associated with the
      testing condition. RESULTS: Adhesion strengths for the nonthermocycled specimens
      were 42.79 +/-14.14 MPa (cast), 37.56 +/-9.18 MPa (milled), and 29.09 +/-6.95 MPa
      (laser-sintered), and, for the thermocycled specimens, 16.52 +/-8.96 MPa (cast),
      22.21 +/-13.25 MPa (milled), and 24.28 +/-10.13 MPa (laser-sintered). Two-way
      ANOVA results indicated no statistically significant differences in adhesion
      among the manufacturing methods (P=.257), but statistically significant
      differences were observed according to both testing conditions (P<.001) and
      interaction between the factors (P=.015). The chi(2) test indicated that the
      failure mode was not associated with the testing condition (thermocycled, P=.280;
      nonthermocycled, P=.240). CONCLUSIONS: The porcelain adhesion values for all the
      materials were adequate for clinical applications. No significant adhesion
      differences were observed between cast, milled, and laser-sintered specimens, or
      among thermocycled and nonthermocycled laser-sintered specimens. However,
      significant adhesion differences were observed among the thermocycled and
      nonthermocycled cast and the milled specimens.

PMID- 24674811
TI  - First-principle calculations analysis of ELNES splitting for Mn3O4 spinels
      related to atomic local symmetry.
AB  - By using a real space multiple scattering method (FEFF code) with a 2 * 2 * 2
      cluster model, we investigated the effects of characteristic Jahn-Teller
      distortion on the electron energy loss near-edge structure (ELNES) of Mn3O4
      spinel. In particular, we examined a correlation between the characteristics of
      the density of state and the ELNES spectral feature as a function of Jahn-Teller
      distortion. To this end, we introduced a geometrical variation approach to an
      Mn3O4 cluster model containing both Mn(3+) and Mn(2+) sites. Upon a prominent
      Jahn-Teller distortion of the Mn(3+)-octahedral site, we resolved the associated
      spectral features of Mn, comprising three peaks that merged upon increasing the
      symmetry of octahedral site from tetragonal (D4h) to cubic (Oh). We have also
      investigated the interplay between the Mn L-edge and corresponding O K-edge
      spectra.

PMID- 24674812
TI  - Unlocking the treasure trove: from genes to schizophrenia biology.
AB  - Significant progress is being made in defining the genetic etiology of
      schizophrenia. As the list of implicated genes grows, parallel developments in
      gene editing technology provide new methods to investigate gene function in model
      systems. The confluence of these two research fields--gene discovery and
      functional biology--may offer novel insights into schizophrenia etiology. We
      review recent advances in these fields, consider the likely obstacles to
      progress, and consider strategies as to how these can be overcome.

PMID- 24674813
TI  - Platelet receptor expression and shedding: glycoprotein Ib-IX-V and glycoprotein
      VI.
AB  - Quantity, quality, and lifespan are 3 important factors in the physiology,
      pathology, and transfusion of human blood platelets. The aim of this review is to
      discuss the proteolytic regulation of key platelet-specific receptors,
      glycoprotein(GP)Ib and GPVI, involved in the function of platelets in hemostasis
      and thrombosis, and nonimmune or immune thrombocytopenia. The scope of the review
      encompasses the basic science of platelet receptor shedding, practical aspects
      related to laboratory analysis of platelet receptor expression/shedding, and
      clinical implications of using the proteolytic fragments as platelet-specific
      biomarkers in vivo in terms of platelet function and clearance. These topics can
      be relevant to platelet transfusion regarding both changes in platelet receptor
      expression occurring ex vivo during platelet storage and/or clinical use of
      platelets for transfusion. In this regard, quantitative analysis of platelet
      receptor profiles on blood samples from individuals could ultimately enable
      stratification of bleeding risk, discrimination between causes of
      thrombocytopenia due to impaired production vs enhanced clearance, and monitoring
      of response to treatment prior to change in platelet count. 

PMID- 24674814
TI  - Pharmacology should be at the centre of all preclinical and clinical studies on
      new psychoactive substances (recreational drugs).
AB  - Despite the publication of a substantial body of preclinical and clinical
      information on recent recreational drugs such as 3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy') and cathinone compounds such as
      mephedrone there remains a disturbing lack of consensus as to how dangerous these
      compounds are to the health of the individual and to society in general. This
      perspective proposes that use of good pharmacological practice should be
      mandatory in all preclinical and clinical studies. Its use will assist both
      translation and reverse translation of information produced in animals and
      clinical subjects. We propose several basic rules to be followed in all future
      studies. Preclinical studies should employ pharmacokinetic-pharmacodynamic
      integration thereby exposing animals to known or calculable drug concentrations.
      This will provide results relevant to pharmacology rather than toxicology and,
      crucially, data relevant to human drug use. Full experimental detail should be
      routinely provided, to allow comparison with other similar work. In clinical
      studies evidence should be provided that the drug under investigation has been
      ingested by the subjects being examined, and details given of all other drugs
      being ingested. Drug-drug interactions are an unavoidable confound but studies of
      a size that allows reliable statistical evaluation and preferably allows sub
      group analysis, particularly by using meta-analysis, should help with this
      problem. This may require greater collaboration between investigative groups, as
      routinely occurs during pharmaceutical clinical trials. Other proposals include
      greater integration of preclinical and clinical scientists in both preclinical
      and clinical studies and changes in the law regarding Good Manufacturing Process
      (GMP) sourcing of drug for human studies. 

PMID- 24674815
TI  - DINO (Diet In Nutrients Out) - an integrated dietary assessment system.
AB  - OBJECTIVE: The current paper describes Diet In Nutrients Out (DINO), an
      integrated dietary assessment system incorporating dietary data entry and
      nutritional analysis within one platform for use in dietary assessment in small
      scale intervention studies to national surveys. DESIGN: DINO contains >6000 food
      items, mostly aggregated composites of branded foods, across thirty-one main food
      groups divided into 151 subsidiary groups for detailed reporting requirements,
      with fifty-three core nutrient fields. SETTING: MRC Human Nutrition Research
      (HNR), Cambridge, UK and MRC Keneba, Gambia. SUBJECTS: DINO is used across
      dietary assessment projects at HNR and MRC Keneba. RESULTS: DINO contains macro-
      and micronutrients as well as additional variables of current research and policy
      interest, such as caffeine, whole grains, vitamin K and added sugars.
      Disaggregated data are available for fruit, vegetables, meat, fish and cheese in
      composite foods, enabling greater accuracy when reporting food consumption or
      assessing adherence to dietary recommendations. Portion sizes are categorised in
      metric and imperial weights, with standardised portion sizes for each age group.
      Regular reviews are undertaken for portion sizes and food composition to ensure
      contemporary relevance. A training programme and a checking schedule are adhered
      to for quality assurance purposes, covering users and data. Eating context
      questions are integrated to record where and with whom the respondent is eating,
      allowing examination between these factors and the foods consumed. CONCLUSIONS:
      An up-to-date quality-assured system for dietary assessment is crucial for
      nutritional surveillance and research, but needs to have the flexibility to be
      tailored to address specific research questions.

PMID- 24674816
TI  - Immediate effects of spinal manipulation on nitric oxide, substance P and pain
      perception.
AB  - Previous studies have analyzed the effects of spinal manipulation on pain
      sensitivity by using several sensory modalities, but to our knowledge, no studies
      have focused on serum biomarkers involved in the nociceptive pathway after spinal
      manipulation. Our objectives were to determine the immediate effect of cervical
      and dorsal manipulation over the production of nitric oxide and substance P, and
      establishing their relationship with changes in pressure pain thresholds in
      asymptomatic subjects. In this single-blind randomized controlled trial, 30
      asymptomatic subjects (16 men) were randomly distributed into 3 groups (n = 10
      per group): control, cervical and dorsal manipulation groups. Blood samples were
      extracted to obtain serum. ELISA assay for substance P and chemiluminescence
      analysis for nitric oxide determination were performed. Pressure pain thresholds
      were measured with a pressure algometer at the C5-C6 joint, the lateral
      epicondyle and the tibialis anterior muscle. Outcome measures were obtained
      before intervention, just after intervention and 2 h after intervention. Our
      results indicated an increase in substance P plasma level in the cervical
      manipulation group (70.55%) when compared with other groups (p < 0.05). This
      group also showed an elevation in the pressure pain threshold at C5-C6 (26.75%)
      and lateral epicondyle level (21.63%) immediately after the intervention (p <
      0.05). No changes in nitric oxide production were observed. In conclusion,
      mechanical stimulus provided by cervical manipulation increases substance P
      levels and pressure pain threshold but does not change nitric oxide
      concentrations. Part of the hypoalgesic effect of spinal manipulation may be due
      to the action of substance P. 

PMID- 24674817
TI  - Whole-body biodistribution and dosimetry estimates of a novel radiotracer for
      imaging of serotonin 4 receptors in brain: [18F]MNI-698.
AB  - INTRODUCTION: A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in
      brain, [18F]MNI-698, was recently developed by our group. Evaluation in nonhuman
      primates indicates the novel radiotracer holds promise as an imaging agent of 5
      HT4 in brain. This paper aims to describe the whole-body biodistribution and
      dosimetry estimates of [18F]MNI-698. METHODS: Whole-body positron emission
      tomography (PET) images were acquired over 240 minutes after intravenous bolus
      injection of [18F]MNI-698 in adult rhesus monkeys. Different models were
      investigated for quantification of radiation absorbed and effective doses using
      OLINDA/EXM 1.0 software. RESULTS: The radiotracer main elimination route was
      found to be urinary and the critical organ was the urinary bladder. Modeling of
      the urinary bladder voiding interval had a considerable effect on the estimated
      effective dose. Normalization of rhesus monkeys' organs and whole-body masses to
      human equivalent reduced the calculated dosimetry values. The effective dose
      ranged between 0.017 and 0.027 mSv/MBq. CONCLUSION: The dosimetry estimates,
      obtained when normalizing organ and whole-body weights and applying the urinary
      bladder model, indicate that the radiation doses from [18F]MNI-698 comply with
      limits and guidelines recommended by key regulatory authorities that govern the
      translation of radiotracers to human clinical trials. The timing of urinary
      bladder emptying should be considered when designing future clinical protocols
      with [18F]MNI-698, in order to minimize the subject absorbed doses.

PMID- 24674818
TI  - Influence of domestication process on immune response to repeated emersion
      stressors in Eurasian perch (Perca fluviatilis, L.).
AB  - Domestication might be a possible way to reduce the physiological response to
      long-term stressors and deleterious effects on immunity. The present study aimed
      to evaluate the chronic immune response induced by repeated emersions and the
      possible impact of domestication by comparing farmed Eurasian perch with short
      (F1) and long (F4) captive-life history. In the first experiment, fish were
      exposed to a single emersion and physiological stress response was measured in
      the short term to characterize fish sensitivity to the tested stressor. Serum
      cortisol and glucose elevated within 6h post-stress and splenosomatic index (SSI)
      decreased within 48h, indicating that the species was affected by emersion
      stressor. In the second experiment, F1 and F4 generations were submitted to
      repeated water emersions (3 times/week during 44days). On day 9, 18 and 44,
      samplings were performed 48h post-stressor to highlight any sustained disruption
      of immune system. Serum cortisol, glucose, SSI and lysozyme activity were
      evaluated and serum proteome was analyzed using 2D-DIGE. Any of the tested
      variables were affected by repeated emersions and proteomic analysis only
      revealed that alpha-2 macroglobulins (a2Ms) were up-regulated in the serum of
      stressed individuals. Domestication also resulted in the up-regulation of five
      a2M isoforms and down-regulation of complement C3 and Ig light chain proteins,
      independently of any stressor exposure. In conclusion, the results suggested that
      repeated emersions are not severe stressors for Eurasian perch, probably
      explaining why domestication had no influence on fish responses. Changes
      associated with domestication are highly complex and certainly need further
      investigations.

PMID- 24674819
TI  - A comparative study of reproductive and metabolic responses to administration of
      exogenous melatonin and aldosterone in xeric and mesic spiny mice populations.
AB  - A comparative study of reproduction revealed differences between desert-adapted
      Acomys russatus and Mediterranean Acomys cahirinus populations with respect to
      the environmental cues used for reproductive activity. Long day (LD) conditions
      were noted as initial reproductive cue for both populations. This research is a
      follow-up affects comparative endocrine and metabolic study in regards to
      reproduction where LD-acclimated mice were treated with, exogenous aldosterone
      (ALDO) and melatonin (MLT). Only the reproductive system of A. russatus females
      was significantly affected by both hormones. In A. cahirinus females, MLT
      decreased leptin levels, while in A. russatus, a treatment with both hormones
      increased leptin levels. In A. russatus males, MLT affects both reproductive and
      metabolic functions. However, in A. cahirinus males, ALDO and MLT treatments
      caused an increase in leptin levels, and a decrease in free fatty acid (FFA)
      levels, respectively. Correlations between leptin and FFA in general were
      affected by both MLT and ALDO treatments in A. russatus males and A. cahirinus
      females. Our results support the general idea, that although the reproductive
      system of A. russatus responded to an osmotic stress, in our case expressed by
      ALDO treatment, which can be considered as an ultimate signal, where, photoperiod
      changes are an initial signal.

PMID- 24674820
TI  - Inorganic phosphate uptake in unicellular eukaryotes.
AB  - BACKGROUND: Inorganic phosphate (Pi) is an essential nutrient for all organisms.
      The route of Pi utilization begins with Pi transport across the plasma membrane.
      SCOPE OF REVIEW: Here, we analyzed the gene sequences and compared the
      biochemical profiles, including kinetic and modulator parameters, of Pi
      transporters in unicellular eukaryotes. The objective of this review is to
      evaluate the recent findings regarding Pi uptake mechanisms in microorganisms,
      such as the fungi Neurospora crassa and Saccharomyces cerevisiae and the parasite
      protozoans Trypanosoma cruzi, Trypanosoma rangeli, Leishmania infantum and
      Plasmodium falciparum. MAJOR CONCLUSION: Pi uptake is the key step of Pi
      homeostasis and in the subsequent signaling event in eukaryotic microorganisms.
      GENERAL SIGNIFICANCE: Biochemical and structural studies are important for
      clarifying mechanisms of Pi homeostasis, as well as Pi sensor and downstream
      pathways, and raise possibilities for future studies in this field.

PMID- 24674821
TI  - Evaluating topological conflict in centipede phylogeny using transcriptomic data
      sets.
AB  - Relationships between the five extant orders of centipedes have been considered
      solved based on morphology. Phylogenies based on samples of up to a few dozen
      genes have largely been congruent with the morphological tree apart from an
      alternative placement of one order, the relictual Craterostigmomorpha, consisting
      of two species in Tasmania and New Zealand. To address this incongruence, novel
      transcriptomic data were generated to sample all five orders of centipedes and
      also used as a test case for studying gene-tree incongruence. Maximum likelihood
      and Bayesian mixture model analyses of a data set composed of 1,934 orthologs
      with 45% missing data, as well as the 389 orthologs in the least saturated,
      stationary quartile, retrieve strong support for a sister-group relationship
      between Craterostigmomorpha and all other pleurostigmophoran centipedes, of which
      the latter group is newly named Amalpighiata. The Amalpighiata hypothesis, which
      shows little gene-tree incongruence and is robust to the influence of among-taxon
      compositional heterogeneity, implies convergent evolution in several
      morphological and behavioral characters traditionally used in centipede
      phylogenetics, such as maternal brood care, but accords with patterns of first
      appearances in the fossil record. 

PMID- 24674822
TI  - Man's best friend equally adapted to high altitudes of tibet.

PMID- 24674823
TI  - Ovarian activity and oocyte quality associated with the biochemical profile of
      serum and follicular fluid from Girolando dairy cows postpartum.
AB  - This study was designed to evaluate the influence of heat stress (HS) on the
      metabolic profile of serum and follicular fluid (FF), ovarian follicle
      development, and oocyte quality of Girolando dairy cows. Oocytes, blood, and FF
      (follicles >=9mm) samples were obtained at 30, 45, 60, 75, and 90 days postpartum
      in the summer and winter seasons. During transvaginal follicular aspiration,
      rectal temperature (RT), body condition score (BCS), number of ovarian follicles,
      and quality of oocytes were recorded. The ambient air temperature (AT) and
      relative humidity (RH) were also recorded to calculate the temperature humidity
      index (THI). Glucose, total cholesterol (TC), triglycerides (TG), urea, sodium
      (Na), potassium (K), and calcium (Ca) concentrations were determined using serum
      and FF samples. The RT, THI, and BCS loss were greater (P<0.01) in the summer;
      however, glucose, Na, and K serum concentrations decreased in the same season
      (P<0.05). Degenerated oocytes were positively associated (P<0.05) with THI
      (r=0.14) and AT (r=0.13), and negatively associated with glucose (r=-0.12) and K
      (r=-0.11) serum concentrations. HS induces metabolic changes, which compromise
      the number of ovarian follicles and the follicular environment, thus resulting in
      morphologically damaged oocytes. 

PMID- 24674824
TI  - Novel SNPs in heat shock protein 70 gene and their association with sperm quality
      traits of Boer goats and Boer crosses.
AB  - The semen quality of bucks affects the reproduction performance of the herd and
      is influenced by genetic and non-genetic factors. Heat shock protein 70 (HSP70)
      is considered as an important gene affecting semen quality traits. The objectives
      of this study are to find single nucleotide polymorphisms in HSP70 coding region
      and their association with semen quality traits on Boer and Boer cross bucks. DNA
      isolated from 53 goats (36 pure South African Boer and 17 Boer crosses) was
      subjected to PCR amplification of the exon 1 region of the caprine HSP70 gene.
      Single-strand conformation polymorphism (SSCP) was used to detect polymorphisms
      and the variant DNA fragments were sequenced. Two synonymous SNPs (74A>C
      (ss836187517) and 191C>G (ss836187518)) were detected. Qualities of fresh and
      post-thaw semen were evaluated for sperm concentration, semen volume, sperm
      motility and velocity traits, live sperm percentage, and abnormal sperm rate. The
      C allele of ss836187517 and G allele of ss836187518 were at higher frequencies in
      both the breeds. The C allele of ss836187517 appeared to be the favorable allele
      for semen concentration, progressive motility of fresh semen, and motility and
      sperm lateral head displacement of post-thaw semen. A negative overdominance was
      observed for ss836187517 alleles on velocity traits of post-thaw semen. The C
      allele of ss836187518 was favorable for sperm concentration and progressive
      motility. Results herein suggest that the SNPs in HSP70 may affect on semen
      quality in tropical regions and specially on the potential of semen for freezing.

PMID- 24674825
TI  - Longer length of stay or readmissions: can we achieve a balance?

PMID- 24674826
TI  - Interhospital transfer of blunt multiply injured patients to a level 1 trauma
      center does not adversely affect outcome.
AB  - BACKGROUND: Stops at nontrauma centers for severely injured patients are thought
      to increase deaths and costs, potentially because of unnecessary imaging and
      indecisive/delayed care of traumatic brain injuries (TBIs). METHODS: We studied
      754 consecutive blunt trauma patients with an Injury Severity Score greater than
      20 with an emphasis on 212 patients who received care at other sites en route to
      our level 1 trauma center. RESULTS: Referred patients were older, more often
      women, and had more severe TBI (all P < .05). After correction for age, sex, and
      injury pattern, there was no difference in the type of TBI, Glasgow Coma Scale
      (GCS) upon arrival at the trauma center, or overall mortality between referred
      and directly admitted patients. GCS at the outside institution did not influence
      promptness of transfer. CONCLUSIONS: Interhospital transfer does not affect the
      outcome of blunt trauma patients. However, the unnecessarily prolonged stay of
      low GCS patients in hospitals lacking neurosurgical care is inappropriate.

PMID- 24674827
TI  - A randomized trial of antibiotic prophylaxis for the prevention of surgical site
      infection after open mesh-plug hernia repair.
AB  - BACKGROUND: The efficacy of antibiotic prophylaxis for the prevention of surgical
      site infection (SSI) after open tension-free inguinal hernia repair remains
      controversial. METHODS: A double-blind, randomized, placebo-controlled trial was
      conducted. Patients who underwent elective open mesh-plug hernia repair were
      eligible for randomization. In the antibiotic prophylaxis group, 1.0 g cefazolin
      was intravenously administrated 30 minutes before the incision. In the placebo
      group, an equal volume of sterile saline was administered. The primary end point
      was the incidence of SSI. RESULTS: A total of 200 patients were enrolled. SSI
      developed in 2 of 100 patients (2%) in the antibiotic prophylaxis group and 13 of
      100 patients (13%) in the placebo group, indicating a significant difference
      between the 2 groups (relative risk ratio, 0.25; 95% confidence interval, 0.070
      to 0.92; P = .003). Other complications occurred in 23 patients: 7 (7%) in the
      antibiotic prophylaxis group and 16 (16%) in the placebo group (P = .046).
      CONCLUSIONS: This study indicates that antibiotic prophylaxis is effective for
      the prevention of SSI after open mesh-plug hernia repair.

PMID- 24674828
TI  - Life after colectomy for fulminant Clostridium difficile colitis: a 7-year follow
      up study.
AB  - BACKGROUND: The long-term prognosis of patients undergoing colectomy for
      fulminant Clostridium difficile colitis has not been well studied. The authors
      present 7-year survival trends in such patients. METHODS: Patients were
      identified through a pathologic database. Medical records were reviewed and
      follow-up phone calls made to determine relevant patient history, longevity, and
      quality of life. RESULTS: The 61 patients identified had mean and median survival
      of 18.1 and 3.2 months, respectively, and 1-year, 2-year, 5-year, and 7-year
      mortality of 68.5%, 79.6%, 88.9%, and 90.7%, respectively. Previous C difficile
      infection, hypotension, requirement of vasopressors, mental status changes,
      elevated arterial lactate, decreased platelet counts, intubation, and longer
      duration on nonoperative therapy were associated with in-hospital mortality.
      There were no factors correlated with long-term survival. CONCLUSIONS: Patients
      who require colectomy for fulminant C difficile colitis have a poor prognosis
      with poor long-term survival and significant morbidity. Although there are
      several factors associated with in-hospital mortality, there were no factors
      correlated with long-term survival.

PMID- 24674829
TI  - Routine restaging PET/CT and detection of initial recurrence in sentinel lymph
      node positive stage III melanoma.
AB  - BACKGROUND: Follow-up of patients with sentinel lymph node-positive stage III
      melanoma uses history, physical exam, and cross-sectional imaging. The aim of
      this study was to evaluate positron emission tomographic (PET)/computed
      tomographic (CT) scans in the detection of recurrence. METHODS: From 2003 to
      2009, a single-institution prospective database of all cutaneous melanoma
      patients was used to identify sentinel lymph node-positive stage III patients
      with disease-free survival >1 year and 1 restaging PET/CT scan. RESULTS: Thirty
      eight patients were identified, with a median follow-up period of 27.5 months.
      Seven (18%) developed recurrence (median time to recurrence, 25 months).
      Recurrences were detected as follows: 3 by patients, 1 by physician, 1 by PET/CT
      scan and lactate dehydrogenase, 1 by PET/CT scan, and 1 by brain magnetic
      resonance imaging. One hundred eight follow-up PET/CT scans were performed. Two
      of 38 patients had asymptomatic metastases detected by routine restaging PET/CT
      scan, and there were 9 scans with false-positive results. CONCLUSIONS: With short
      follow-up, the utility of routine PET/CT scans in identifying unsuspected
      recurrence in patients with sentinel lymph node-positive stage III melanoma
      appears minimal.

PMID- 24674830
TI  - Type II endometrial cancer in Hispanic women: tumor characteristics, treatment
      and survival compared to non-Hispanic white women.
AB  - OBJECTIVES: To compare survival of Hispanic white (HW) and non-Hispanic white
      (NHW) women with type II endometrial adenocarcinoma (EC). METHODS: Patients with
      serous, clear cell or grade 3 endometrioid EC were identified from the
      Surveillance, Epidemiology, and End Results (SEER) program 1988-2009 and were
      divided into HW and NHW. HW were subdivided into natives and immigrants. RESULTS:
      Of the 14,434 women, 13,012 (90.2%) were NHW and 1422 (9.8%) were HW. HW were
      younger than NHW (mean 63 vs. 68years, p<0.001). A higher proportion of HW
      presented with late stage disease than NHW (43.8% vs. 36.6%, p=0.04). Performing
      lymphadenectomy was not different but HW were more likely to have positive lymph
      nodes than NHW (27.6% vs. 23.1%, p=0.02). Further, HW were less likely to receive
      radiation than NHW (39.5% vs. 42.3%, p=0.04). No difference in clinicopathologic
      characteristics was found between immigrant and native HW. In multivariate models
      adjusting for age, stage, histology, surgical treatment, extent of
      lymphadenectomy, and radiation therapy, no difference in overall survival (OS)
      (HR 1.06, 95% CI 0.97-1.16, p=0.19) and cancer-specific survival (CSS) (HR 1.02,
      95% CI 0.91-1.14, p=0.75) was found between HW and NHW. Interestingly, immigrant
      HW had better OS (HR 0.74, 95% CI 0.62-0.89, p<0.001) and CSS (HR 0.72, 95% CI
      0.58-0.90, P=0.003) than native HW. CONCLUSIONS: Although they were more likely
      to present with advanced stage and positive nodal disease, no difference in
      outcome was noted between Hispanic and non-Hispanic whites with EC.
      Interestingly, immigrant HW had more favorable outcome compared to native HW.

PMID- 24674833
TI  - NHS hospitals should imitate Sainsbury's Local and Tesco Metro, hospital chief
      says.

PMID- 24674831
TI  - Impact of socioeconomic status and ethnic enclave on cervical cancer incidence
      among Hispanics and Asians in California.
AB  - OBJECTIVE: This study aimed to evaluate the incidence of cervical cancer by
      nativity [United States (US) versus non-US], neighborhood socioeconomic status
      and ethnic enclave among Hispanics and Asians in California. METHODS: Using data
      from the California Cancer Registry, information on all primary invasive cervical
      cancer (Cca) patients diagnosed in California from January 1, 1990 through
      December 31, 2004 was obtained. We analyzed the influence of enclave,
      socioeconomic status and nativity on Cca incidence. RESULTS: Among the 22,189 Cca
      cases diagnosed between 1990 and 2004, 50% were non-Hispanic white, 39% Hispanic
      and 11% Asian women, and 63% US-born. Seventy percent of the Cca cases were
      squamous cell carcinoma, 19% adenocarcinoma and 11% other histologies. Higher
      incidence of Cca was observed in high enclave (76%) and low socioeconomic status
      (70%) neighborhoods. By ethnic group, US-born women showed lower rates of
      squamous cell carcinoma compared to foreign-born women. Hispanics living in low
      socioeconomic and high enclave had 12.7 times higher rate of Cca than those
      living in high socioeconomic, low enclave neighborhoods. For Asian women
      incidence rates were 6 times higher in the low socioeconomic, high enclave
      neighborhoods compared to those living in high socioeconomic, low enclave
      neighborhoods. CONCLUSION: More targeted outreach to increase Pap smear screening
      and human papilloma virus vaccination for women living in high enclave
      neighborhoods can help decrease the incidence of Cca in these groups of women.

PMID- 24674832
TI  - Estrogen receptor expression and increased risk of lymphovascular space invasion
      in high-grade serous ovarian carcinoma.
AB  - OBJECTIVE: Recent studies have demonstrated that lymphovascular space invasion
      (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis
      and poor clinical outcome of women with epithelial ovarian cancer. Given the
      suspected role of estrogen in promoting ovarian cancer metastasis, we examined
      potential links between estrogen receptor and LVSI in high-grade serous ovarian
      carcinoma. METHODS: Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA
      ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade
      serous ovarian carcinoma samples obtained at primary cytoreductive surgery.
      Biomarker expression was correlated to LVSI and survival outcomes. RESULTS: LVSI
      was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested
      biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53
      (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression
      was positively correlated to PR expression (r=0.31, p=0.001). LVSI was only
      correlated with ER (odds ratio 6.27, 95%CI 1.93-20.4, p=0.002) but not with other
      biomarkers. In multivariate analysis, ER remained significantly associated with
      LVSI (p=0.039). LVSI remained a significant prognostic factor for decreased
      progression-free survival (HR 3.01, 95%CI 1.54-5.88, p=0.001) and overall
      survival (HR 2.69, 95%CI 1.18-6.23, p=0.021) while ER-expression did not remain
      as a significant variable in multivariate analysis. CONCLUSION: Our data
      demonstrated that estrogen receptor was positively correlated with LVSI that was
      an independent prognostic indicator of poor survival outcomes of high-grade
      serous ovarian carcinoma. This study emphasizes the importance of estrogen
      pathway in promoting lymphatic or vascular spread of high-grade serous ovarian
      carcinoma.

PMID- 24674834
TI  - [The voice of women subjected to female genital mutilation in the Region of
      Murcia (Spain)].
AB  - OBJECTIVE: To explore the perceptions of a group of women who underwent female
      genital mutilation on the impact of this practice on their sexual and
      reproductive health. METHODS: We performed a phenomenological qualitative study
      in a sample of 9 sub-Saharan Africa women, whose mean age was 30 years old and
      who had lived in Spain for 1 to 14 years. These women underwent genital
      mutilation in their countries of origin. Data was collected using a socio
      demographic survey and an in-depth, structured personal interview. Subsequently,
      we performed a thematic discourse analysis. RESULTS: The discourses were grouped
      into four categories related to participants' perceptions of female genital
      mutilation. These categories were intimate relationships, pregnancy, childbirth,
      and social impact. CONCLUSIONS: The practice of female genital mutilation is
      maintained due to social and family pressure, transmitted from generation to
      generation and silenced by women themselves. This practice affects their sexual
      and reproductive health, as demonstrated by anorgasmia and dyspareunia. The women
      were satisfied with the healthcare received during pregnancy and childbirth.
      Nevertheless, most of them were not satisfied with family planning.

PMID- 24674836
TI  - Reprint of: Role of enteric neurotransmission in host defense and protection of
      the gastrointestinal tract.
AB  - Host defense is a vital role played by the gastrointestinal tract. As host to an
      enormous and diverse microbiome, the gut has evolved an elaborate array of
      chemical and physicals barriers that allow the digestion and absorption of
      nutrients without compromising the mammalian host. The control of such barrier
      functions requires the integration of neural, humoral, paracrine and immune
      signaling, involving redundant and overlapping mechanisms to ensure, under most
      circumstances, the integrity of the gastrointestinal epithelial barrier. Here we
      focus on selected recent developments in the autonomic neural control of host
      defense functions used in the protection of the gut from luminal agents, and
      discuss how the microbiota may potentially play a role in enteric
      neurotransmission. Key recent findings include: the important role played by
      subepithelial enteric glia in modulating intestinal barrier function,
      identification of stress-induced mechanisms evoking barrier breakdown, neural
      regulation of epithelial cell proliferation, the role of afferent and efferent
      vagal pathways in regulating barrier function, direct evidence for bacterial
      communication to the enteric nervous system, and microbial sources of enteric
      neurotransmitters. We discuss these new and interesting developments in our
      understanding of the role of the autonomic nervous system in gastrointestinal
      host defense. 

PMID- 24674835
TI  - Autonomic modulation in a patient with syncope and paroxysmal atrial
      fibrillation.
AB  - We report a case of a patient with recurrent syncope and paroxysmal atrial
      fibrillation whose clinical status greatly improved after a period of orthostatic
      training. The potential efficacy of this non-pharmacological measure in
      modulating the autonomic tone is discussed below.

PMID- 24674837
TI  - The effect of fluoxetine on ischemia-reperfusion after aortic surgery in a rat
      model.
AB  - BACKGROUND: Aortic ischemia-reperfusion (IR) is an important factor in the
      development of postoperative acute lung injury after abdominal aortic surgery.
      The aim of the present study was to examine the effect of fluoxetine (Flx), a
      selective serotonin reuptake inhibitor widely used as a preoperative anxiolytic,
      on lung injury induced by abdominal aortic IR in rats. METHODS: Wistar rats were
      randomized into three groups (n = 7 per group): (1) control (sham laparotomy);
      (2) IR without Flx (60-min ischemia and 120-min reperfusion); (3) IR with Flx
      (Flx + IR) (Flx 20 mg/kg/d, intraperitoneally for 3 d before surgery). Lung
      tissue samples and bronchoalveolar lavage (BAL) were obtained for biochemical
      analysis of oxidative status. Ischemia-modified albumin (IMA) level and protein
      concentrations in BAL and lung wet to dry weight ratios were determined.
      Histologic evaluation of the lung tissues was also performed. RESULTS: IR without
      Flx led to significant increase in lipid hydroperoxide, malondialdehyde, and pro
      oxidant-antioxidant balance and decrease in superoxide dismutase, glutathione,
      and ferric reducing antioxidant power activities (P < 0.05 versus control),
      whereas Flx was able to restore these parameters (P > 0.05 versus control) and
      decrease IMA level (P < 0.01 versus control) and protein concentration (P < 0.05
      versus control) in BAL and wet to dry lung weight ratio. Histologic evaluation
      showed that Flx attenuated the morphologic changes associated with lung injury.
      CONCLUSIONS: The results indicate that Flx confers protection against aortic IR
      induced lung oxidative stress and cellular integrity. IMA levels in BAL may be
      used as a follow-up marker for the efficacy of treatment in lung injury.

PMID- 24674838
TI  - Preconditioning renoprotective effect of isoflurane in a rat model of virtual
      renal transplant.
AB  - BACKGROUND: The development of warm-cold ischemia-reperfusion (IR) injury of the
      kidney grafts is inevitable during renal transplantation. However, there is
      currently no definite renoprotective strategy available in the protection of the
      graft tissue. In the present study, we compared the renal protection of
      preconditioning isoflurane with N-acetylcysteine (NAC) in a novel rat model of
      warm-cold renal IR injury. MATERIALS AND METHODS: Adult Sprague-Dawley rats were
      randomly assigned to receive inhaled isoflurane (1.5% for 2 h), NAC (1 g/kg,
      intra-arterial injection) or placebo before the induction of brief warm ischemia
      (10 min) followed by cold ischemia (45 min) periods. Plasma levels of creatinine
      and tissue inflammatory reaction in the kidney were analyzed 72 h after
      reperfusion. RESULTS: Elevated plasma level of creatinine and urea indicated the
      development of acute renal injury secondary to IR injury. The creatinine levels
      were reduced in animals pretreated with inhaled isoflurane and NAC, and the level
      was more significantly decreased in the isoflurane-treated group. Preconditioning
      with volatile isoflurane also significantly suppressed the tissue myeloperoxidase
      activity and expression of the inducible nitric oxide synthase. Immunostaining
      confirmed that myeloperoxidase expression was most significantly attenuated in
      the glomerulus and peritubular capillaries of rats pre-exposed to isoflurane.
      CONCLUSIONS: We present the first study demonstrating that the administration of
      volatile isoflurane before induction of experimental warm-cold renal IR injury
      provides preconditioning renoprotective effect, which is superior to the
      treatment with NAC. The beneficial renoprotective effect of isoflurane is most
      likely mediated by attenuation of proinflammatory reaction in the injured kidney.

PMID- 24674839
TI  - Aprotinin reduces oxidative stress induced by pneumoperitoneum in rats.
AB  - BACKGROUND: Ischemia-reperfusion injury induced by pneumoperitoneum is a well
      studied entity, which increases oxidative stress during laparoscopic operations.
      The reported anti-inflammatory action of aprotinin was measured in a
      pneumoperitoneum model in rats for the first time in this study. MATERIALS AND
      METHODS: A total of 60 male Albino Wistar rats were used in our protocol.
      Prolonged pneumoperitoneum (4 h) was applied, causing splanchnic ischemia and a
      period of reperfusion with a duration of 60 or 180 min followed. Several
      cytokines and markers of oxidative stress were measured in liver, small
      intestine, and lungs to compare the aprotinin group with the control group.
      Tissue inflammation was also evaluated and compared between groups using a five
      scaled histopathologic score. RESULTS: In aprotinin group values of biochemical
      markers (tumor necrosis factor alpha, interleukin 6, endothelin 1, C reactive
      protein, pro-oxidant-antioxidant balance, and carbonyl proteins) were lower in
      all tissues studied. Statistical significance was greater in liver and lungs (P <
      0.05). Histopathologic examination revealed significant difference between
      control and aprotinin groups in all tissues examined. Aprotinin groups showed
      mild to moderate lesions, while in control groups severe to very severe
      inflammation was present. Aprotinin subgroup with prolonged reperfusion period
      (180 min) showed milder lesions in all tissues than the rest of the groups.
      CONCLUSIONS: Aprotinin reduced inflammatory response and oxidative stress induced
      by pneumoperitoneum in liver, small intestine, and lungs.

PMID- 24674840
TI  - How to interpret the bile culture results of patients with biliary tract
      infections.
AB  - BACKGROUND/GOALS: Bile is normally sterile, but the presence of organisms in the
      bile does not necessarily imply an active infection. We wonder what the
      significance of bile culture results on antibiotics choice in cholangitis with
      negative blood culture. The aim of this study was to compare organisms cultured
      from bile with those from blood in bacteremic biliary tract infection and to
      evaluate factors associated with concordance between blood and bile isolates.
      METHODS: Between 2000 and 2010, 266 positive blood cultures with concomitant bile
      culture in bacteremic biliary tract infection were identified. Follow-up bile
      specimens obtained after negative conversion of blood culture and clinical
      recovery from acute infection were collected for supplementary analysis. RESULTS:
      Of the 266 events, 258 showed positive bile culture. Of the 258 bile samples, 80
      yielded the same organisms with blood, 129 showed partial agreement and 49
      yielded completely different organisms with blood. Only the number of organism
      was found to be independently associated with concordance. Of the 529 organisms
      isolated from bile, 227 were found in blood and gram-negative organisms showed
      higher rate of coincidence than gram-positive organisms. Of the 84 follow-up bile
      sample, 94% showed persistent positive culture and higher rate of antibiotics
      resistance than initial bile culture. CONCLUSIONS: More than half of the
      organisms isolated from bile, especially gram-positive organisms, are not likely
      to be true pathogens. But single organism cultured from bile has clinical
      significance. Routine follow-up bile culture in patients showing clinical
      improvement is not necessary.

PMID- 24674841
TI  - Thymosinbeta4: a novel assessed biomarker of the prognosis of acute-on-chronic
      liver failure patient?
AB  - BACKGROUND AND AIM: In the previous study, we found serum thymosin beta4 (Tbeta4)
      levels were associated with mortality in liver failure patients. In this study,
      we try to evaluate the prognostic value of Tbeta4 in acute-on-chronic liver
      failure (AoCLF) patients by comparing with the Child-Pugh (CTP) and Model for End
      Stage Liver Disease (MELD) scores. METHODS: Serum Tbeta4 levels were measured by
      enzyme-linked immunosorbent assay (ELISA), and the CTP and MELD scores were
      calculated for each patient. RESULTS: Serum Tbeta4 levels of AoCLF patients
      [0.4120 (0.2447-0.7492)MUg/mL] were lower than healthy controls [9.2710 (5.1660
      13.2485)MUg/mL] (P<0.001). AoCLF patients were divided into survival and death
      group. Compared to survivors, lower Tbeta4 concentrations, higher CTP and MELD
      scores (P<0.001, respectively) were observed in AoCLF patients who died. There
      were negative correlations between Tbeta4 levels and CTP scores (P<0.001), MELD
      scores (P<0.001). A CTP score of 11.5, a MELD score of 21.63 and a Tbeta4
      concentration of 0.3840MUg/mL were identified as the cut-off values for the
      stratification of AoCLF patients. MELD>=21.63 combined with Tbeta4<0.3840MUg/mL
      can more exactly discriminate between the patients who would survive and die.
      CONCLUSIONS: Serum Tbeta4 concentration has appreciable value to evaluate the
      short-term prognosis of AoCLF patients, although Tbeta4 is not superior to MELD.
      The combination of Tbeta4 and MELD scores are more effective in assessing the
      prognosis of AoCLF patients.

PMID- 24674842
TI  - Augusta Dejerine-Klumpke (1859-1927): an extraordinary neurologist and an
      inspiration for all women in medical careers.

PMID- 24674843
TI  - Post-varicella angiopathy: a series of 4 patients with focus on virologic and
      neuroimaging findings.
AB  - BACKGROUND: Post-varicella angiopathy is an important cause of childhood stroke
      and follows a particular pattern. Specific treatment guidelines have not been
      developed because of a lack of epidemiological, laboratory, and neuroimaging
      data. Prospective randomized controlled trials evaluating different treatment
      strategies have not been performed, and expert opinions on diagnostic criteria,
      prognosis, and treatment are diverging. METHODS: This case series describes the
      clinical course, laboratory, and neuroimaging findings of four children with post
      varicella angiopathy, who all underwent cerebrospinal fluid assessment and
      received antiviral, immunosuppressive, and antiplatelet treatment. RESULTS:
      Cerebrospinal fluid analysis was positive for varicella-zoster virus markers in
      three children. At follow-up, three children had a mild hemiparesis and one child
      had no neurological symptoms. Neuroimaging showed complete vascular remission in
      three patients and improvement in one. CONCLUSIONS: Systematic search for
      virologic markers in cerebrospinal fluid will contribute to the understanding of
      the pathogenesis of idiopathic childhood stroke and can be considered as a
      prerequisite for the development of clear diagnostic criteria and relevant
      treatment strategies for post-varicella angiopathy. The role of antiviral and
      immunosuppressive medication needs to be clarified.

PMID- 24674844
TI  - Paving the COWpath: data-driven design of pediatric order sets.
AB  - OBJECTIVE: Evidence indicates that users incur significant physical and cognitive
      costs in the use of order sets, a core feature of computerized provider order
      entry systems. This paper develops data-driven approaches for automating the
      construction of order sets that match closely with user preferences and workflow
      while minimizing physical and cognitive workload. MATERIALS AND METHODS: We
      developed and tested optimization-based models embedded with clustering
      techniques using physical and cognitive click cost criteria. By judiciously
      learning from users' actual actions, our methods identify items for constituting
      order sets that are relevant according to historical ordering data and grouped on
      the basis of order similarity and ordering time. We evaluated performance of the
      methods using 47,099 orders from the year 2011 for asthma, appendectomy and
      pneumonia management in a pediatric inpatient setting. RESULTS: In comparison
      with existing order sets, those developed using the new approach significantly
      reduce the physical and cognitive workload associated with usage by 14-52%. This
      approach is also capable of accommodating variations in clinical conditions that
      affect order set usage and development. DISCUSSION: There is a critical need to
      investigate the cognitive complexity imposed on users by complex clinical
      information systems, and to design their features according to 'human factors'
      best practices. Optimizing order set generation using cognitive cost criteria
      introduces a new approach that can potentially improve ordering efficiency,
      reduce unintended variations in order placement, and enhance patient safety.
      CONCLUSIONS: We demonstrate that data-driven methods offer a promising approach
      for designing order sets that are generalizable, data-driven, condition-based,
      and up to date with current best practices.

PMID- 24674846
TI  - Acute but not sustained aromatase inhibition displays antidepressant properties.
AB  - Aromatase inhibitors block the conversion of androgens to oestrogens and are used
      for the treatment of hormone-responsive breast cancer in menopause and recently
      also in premenopausal women. We investigate whether decreased oestrogen synthesis
      following aromatase inhibition leads to a depressive-like behavioural response in
      cycling female rats. Using the forced swim test (FST) we estimate the response of
      acute (three injections in 24 h) and sustained (7 d) letrozole and fluoxetine
      administration. Acute aromatase inhibition decreases immobility duration in the
      FST, indicating its antidepressant potential. Instead, sustained aromatase
      inhibition did not show such antidepressant potential. Testosterone elevation
      associates with the decreased depressive behaviour in the FST following acute
      letrozole treatment, but interestingly progesterone explains the increased
      swimming behaviour. Present findings may have potential implications for women
      treated with aromatase inhibitors, especially before menopause, as well as for
      the role of gonadal hormones in the expression of depressive symptoms and
      antidepressant response. 

PMID- 24674847
TI  - Modulation of neuronal activity with cue-invariant shape discrimination in the
      primate superior temporal sulcus.
AB  - Shape perception can be achieved based on various cues such as luminance, color,
      texture, depth and motion. To investigate common neural mechanisms underlying
      shape perception cued by various visual attributes, we examined single-neuron
      activity in the monkey anterior superior temporal sulcus (STS) in response to
      shapes defined by luminance and motion cues during shape discrimination. We found
      cortical mapping with respect to selectivity for shapes as well as for direction
      of motion in the STS. About 90% of shape-selective neurons were located in the
      lower bank of STS (lSTS) assigned to the ventral pathway, while about 80% of
      direction-selective neurons existed in the upper bank of STS (uSTS) assigned to
      the dorsal pathway. The neurons showing selectivity for both shape and motion
      coexisted in lSTS as well as uSTS. This result indicates that integration or
      convergence of shape information and motion information can occur in both banks
      of STS. About 90% of STS neurons showing selectivity both for shapes defined by
      luminance cue and for shapes defined by motion cue were located in lSTS. They
      showed a highly similar shape preference between the different visual attributes,
      indicating cue-invariant shape selectivity. The cue-invariant shape-selectivity
      was modulated with target selection as well as with discrimination performance of
      monkeys. These results suggest that lSTS could be involved in cue-invariant shape
      discrimination, but not the uSTS. 

PMID- 24674849
TI  - Epigenetics and chemical safety - concluding remarks.

PMID- 24674850
TI  - High cholesterol intake is associated with elevated risk of type 2 diabetes
      mellitus - a meta-analysis.
AB  - BACKGROUND & AIMS: Some foods rich in cholesterol are associated with high risk
      of type 2 diabetes (T2D). To confirm the association between dietary cholesterol
      intake and T2D risk, we performed a meta-analysis of observational studies.
      METHODS: We searched for longitudinal studies that provided data on the relative
      risk (RR) for T2D in relation to the cholesterol intake level using MEDLINE (from
      1950 for July 10, 2013) and EMBASE (from 1974 to July 10, 2013). The RR for the
      highest vs. lowest cholesterol intake category or for an increment of 100 mg/day
      in cholesterol consumption was pooled with an inverse-variance method. RESULTS:
      Five studies met the inclusion criteria. Compared with the lowest category, the
      highest category had a significantly higher association with T2D risk (RR [95%
      confidence interval (CI)], 1.25 [1.16-1.36]). The pooled RR for a 100-mg/day
      increment was also significant (RR [95% CI], 1.11 [1.06-1.15]). CONCLUSION:
      Current meta-analysis suggested that high intake of cholesterol was positively
      associated with future T2D risk.

PMID- 24674848
TI  - Neonatal ketamine exposure causes impairment of long-term synaptic plasticity in
      the anterior cingulate cortex of rats.
AB  - Ketamine, a dissociative anesthetic most commonly used in many pediatric
      procedures, has been reported in many animal studies to cause widespread
      neuroapoptosis in the neonatal brain after exposure in high doses and/or for a
      prolonged period. This neurodegenerative change occurs most severely in the
      forebrain including the anterior cingulate cortex (ACC) that is an important
      brain structure for mediating a variety of cognitive functions. However, it is
      still unknown whether such apoptotic neurodegeneration early in life would
      subsequently impair the synaptic plasticity of the ACC later in life. In this
      study, we performed whole-cell patch-clamp recordings from the ACC brain slices
      of young adult rats to examine any alterations in long-term synaptic plasticity
      caused by neonatal ketamine exposure. Ketamine was administered at postnatal day
      4-7 (subcutaneous injections, 20mg/kg given six times, once every 2h). At 3
      4weeks of age, long-term potentiation (LTP) was induced and recorded by
      monitoring excitatory postsynaptic currents from ACC slices. We found that the
      induction of LTP in the ACC was significantly reduced when compared to the
      control group. The LTP impairment was accompanied by an increase in the alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated excitatory
      synaptic transmission and a decrease in GABA inhibitory synaptic transmission in
      neurons of the ACC. Thus, our present findings show that neonatal ketamine
      exposure causes a significant LTP impairment in the ACC. We suggest that the
      imbalanced synaptic transmission is likely to contribute to ketamine-induced LTP
      impairment in the ACC. 

PMID- 24674851
TI  - Renal denervation and regression of left ventricular hypertrophy.

PMID- 24674854
TI  - Socioeconomic inequalities in premature mortality in Colombia, 1998-2007: the
      double burden of non-communicable diseases and injuries.
AB  - OBJECTIVES: Non-communicable diseases have become the leading cause of death in
      middle-income countries, but mortality from injuries and infections remains high.
      We examined the contribution of specific causes to disparities in adult premature
      mortality (ages 25-64) by educational level from 1998 to 2007 in Colombia.
      METHODS: Data from mortality registries were linked to population censuses to
      obtain mortality rates by educational attainment. We used Poisson regression to
      model trends in mortality by educational attainment and estimated the
      contribution of specific causes to the Slope Index of Inequality. RESULTS: Men
      and women with only primary education had higher premature mortality than men and
      women with post-secondary education (RRmen=2.60, 95% confidence interval [CI]:
      2.56, 2.64; RRwomen=2.36, CI: 2.31, 2.42). Mortality declined in all educational
      groups, but declines were significantly larger for higher-educated men and women.
      Homicide explained 55.1% of male inequalities while non-communicable diseases
      explained 62.5% of female inequalities and 27.1% of male inequalities. Infections
      explained a small proportion of inequalities in mortality. CONCLUSION: Injuries
      and non-communicable diseases contribute considerably to disparities in premature
      mortality in Colombia. Multi-sector policies to reduce both interpersonal
      violence and non-communicable disease risk factors are required to curb mortality
      disparities.

PMID- 24674853
TI  - Involving community stakeholders to increase park use and physical activity.
AB  - OBJECTIVE: The aim of this study is to describe implementation of a randomized
      controlled trial of community-based participatory research (CBPR) approaches to
      increase park use and physical activity across 33 diverse neighborhoods in Los
      Angeles. METHODS: Fifty parks were randomly assigned based on park size,
      facilities and programs, and neighborhood socio-demographic characteristics to:
      park director (PD, 17 parks); PD and park advisory board of interested community
      members (PD+PAB, 16 parks); and no-intervention control (17 parks) arms. Between
      2007 and 2012, PDs and PABs from the 33 intervention parks participated in
      community engagement, baseline assessment, marketing training, intervention
      design and implementation, and follow-up assessment. RESULTS: Intervention parks
      (PD and PD+PAB) invested in new and diversified signage, promotional items,
      outreach or support for group activities like fitness classes and walking clubs,
      and various marketing strategies. Scaling up CBPR methods across parks in 33
      diverse neighborhoods was challenging. Working with departmental management and
      established structures for community input (PABs) and park policy (PDs)
      facilitated implementation and sustainability. CONCLUSION: Scaling up CBPR
      methods across diverse communities involved tradeoffs. CBPR is useful for
      tailoring research and enhancing community impact and sustainability, but more
      work is needed to understand how to conduct multi-site trials across diverse
      settings using CBPR.

PMID- 24674855
TI  - Vitamin D and brain volumetric changes: Systematic review and meta-analysis.
AB  - Vitamin D has multiple functions in the nervous system. Our objective was to
      systematically review and quantitatively synthesize evidence on the location and
      nature of brain morphometric changes linked to vitamin D depletion or repletion.
      A Medline search was conducted in February 2014, without limit of date and
      language restriction, using the MeSH terms "Vitamin D" OR "Ergocalciferols"
      combined with "Brain Mapping" OR "Magnetic Resonance Imaging" OR "Tomography, X
      ray Computed" OR "Tomography, Emission-Computed, Single-Photon" OR "Positron
      Emission Tomography" OR "Nuclear Medicine" OR "Radionucleide Imaging". Of the 376
      selected studies, nine observational studies - two animal and seven human studies
      - met the selection criteria. The number of participants ranged from 20 to 333
      (40-79% female). Three studies were eligible for fixed-effects meta-analysis of
      bias-corrected effect size of the difference in lateral ventricle volume between
      cases with vitamin D depletion and controls. Results showed that vitamin D
      depletion was associated with lower brain volume, specifically larger lateral
      ventricles. The pooled effect size was 1.01 [95% CI: 0.62; 1.41], a 'large'
      effect size indicating that the ventricle volume was 1.01 SD higher with vitamin
      D depletion. Results on brain subvolumes were mixed, and indicated that brain
      atrophy with vitamin D depletion could be explained not by temporal lobe atrophy
      but rather by loss of matter at the cranial vertex, possibly in the precuneus
      cortex. In conclusion, despite increasing evidence arguing for an action of
      vitamin D in the brain, data is sparse regarding brain morphological changes
      related to vitamin D depletion. The retrieved association between vitamin D
      depletion and brain atrophy provides a scientific base for vitamin D replacement
      trials.

PMID- 24674856
TI  - The role of muscle mass in exercise-induced hyperemia.
AB  - Exercise-induced hyperemia is often normalized for muscle mass, and this value is
      sometimes evaluated at relative exercise intensities to take muscle recruitment
      into account. Therefore, this study sought to better understand the impact of
      muscle mass on leg blood flow (LBF) during exercise. LBF was assessed by Doppler
      ultrasound in 27 young healthy male subjects performing knee-extensor (KE)
      exercise at three absolute (5, 15, and 25 W) and three relative [20, 40, and 60%
      of maximum KE (KEmax)] workloads. Thigh muscle mass (5.2-8.1 kg) and LBF were
      significantly correlated at rest (r = 0.54; P = 0.004). Exercise-induced
      hyperemia was linearly related to absolute workload, but revealed substantial
      between-subject variability, documented by the coefficient of variation (5 W:
      17%; 15 W: 16%; 25 W: 16%). Quadriceps muscle mass (1.5-2.7 kg) and LBF were not
      correlated at 5, 15, or 25 W (r = 0.09-0.01; P = 0.7-0.9). Normalizing blood flow
      for quadriceps muscle mass did not improve the coefficient of variation at each
      absolute workload (5 W: 21%; 15 W: 21%; 25 W: 22%), while the additional
      evaluation at relative exercise intensities resulted in even greater variance
      (20% KEmax: 29%; 40% KEmax: 29%; 60% KEmax: 27%). Similar findings were
      documented when subjects were parsed into high and low aerobic capacity. Thus, in
      contrast to rest, blood flow during exercise is unrelated to muscle mass, and
      simply normalizing for muscle mass or comparing normalized blood flow at a given
      relative exercise intensity has no effect on the inherent blood flow variability.
      Therefore, during exercise, muscle mass does not appear to be a determinant of
      the hyperemic response. 

PMID- 24674857
TI  - Structure of cortical cytoskeleton in fibers of mouse muscle cells after being
      exposed to a 30-day space flight on board the BION-M1 biosatellite.
AB  - The aim of the work was to analyze changes in the organization of the cortical
      cytoskeleton in fibers of the mouse soleus muscle, tibialis anterior muscle and
      left ventricular cardiomyocytes after completion of a 30-day space flight on
      board the BION-M1 biosatellite (Russia, 2013). The transversal stiffness of the
      cortical cytoskeleton of the cardiomyocytes and fibers of the skeletal muscles
      did not differ significantly within the study groups compared with the vivarium
      control group. The content of beta- and gamma-actin in the membranous fraction of
      proteins in the left ventricular cardiomyocytes did not differ significantly
      within all study groups and correlated with the transversal stiffness. A similar
      situation was revealed in fibers of the soleus muscle and tibialis anterior
      muscle. At the same time, the content of beta-actin in the cytoplasmic fraction
      of proteins was found to be decreased in all types of studied tissues compared
      with the control levels in the postflight group, with lowered beta-actin gene
      expression rates in the postflight group. After completion of the space flight,
      the content of alpha-actinin-4 was found to be reduced in the membranous fraction
      of proteins from the mouse cardiomyocytes, while its content in the cytoplasmic
      fraction of proteins did not change significantly. Furthermore, gene expression
      rates of this protein were decreased at the time of dissection (it was started
      after 13 h after landing). At the same time, the content of alpha-actinin-1
      decreased in the membranous fraction and increased in the cytoplasmic fraction of
      proteins from the soleus muscle fibers. 

PMID- 24674858
TI  - Effect of change in fluid distribution in segments in hemodialysis patients at
      different ultrafiltration rates on accuracy of whole body bioimpedance
      measurement.
AB  - This study explored divergence (error) between ultrafiltration volumes (UFV) and
      intradialytic changes in extracellular volume (DeltaECV) in hemodialysis (HD)
      patients measured by whole body (wBIS) and sum of segmental bioimpedance
      spectroscopy (sBIS). The primary aim of the study was to evaluate the effect of
      different ultrafiltration rates (UFR) on error of estimation of DeltaECV by
      changes in their distribution in body segments (arm, trunk, and leg). Forty-four
      HD patients (26 men, age 63.5 +/- 14.3 yr) were studied twice in the same week
      following high and low UFR treatments. DeltaECV and distributions (segmental
      DeltaECV/Sigmasegmental DeltaECV, %) in arm, trunk, and leg were measured.
      DeltaECV by wBIS underestimated UFV (0.58 +/- 0.43 in high vs. 0.36 +/- 0.5
      liters at low UFR; P < 0.001, respectively); however, using sBIS no significant
      difference between UFV and DeltaECV was present. Divergence using wBIS but not
      sBIS correlated positively with UFR. DeltaECV distribution in trunk and leg at
      high UFR (44.1 +/- 8.3, 47.2 +/- 8.5, %) differed significantly (P < 0.01) from
      low UFR (36 +/- 15.7, 53.8 +/- 14.7) respectively, but in arm did not differ
      between UFR. Primary sources of whole body resistance are arms and legs. Due to
      different cross-sectional areas between trunk and limbs, wBIS is insensitive to
      detection of changes in trunk volume. At higher UFR, plasma water was rapidly and
      largely removed from the trunk but with only a small change in whole body
      resistance. As a result, accuracy of estimation of ECV by wBIS is further
      decreased by high UFR, while sBIS remains accurate using separate measurements of
      segmental volumes.

PMID- 24674859
TI  - Chronic vagal nerve stimulation improves baroreflex neural arc function in heart
      failure rats.
AB  - We tested whether 6-wk vagal stimulation (VS) treatment improved open-loop
      baroreflex function in rats after myocardial infarction (MI). The following three
      groups of Sprague-Dawley rats were examined: normal control (NC, n = 9), MI with
      no treatment (MI-NT, n = 8), and MI treated with VS (MI-VS, n = 7). Under
      anesthesia, a stepwise input ranging from 60 to 180 mmHg was imposed on isolated
      carotid sinus baroreceptor regions, while the responses in splanchnic sympathetic
      nerve activity (SNA) and arterial pressure (AP) were measured. The response range
      of percent SNA was greater in the MI-VS than in the MI-NT group (63.8 +/- 4.9%
      vs. 33.1 +/- 3.8%, P < 0.01). The slope of the AP response to percent SNA was not
      different between the MI-VS and MI-NT groups (0.611 +/- 0.076 vs. 0.781 +/- 0.057
      mmHg/%). The difference in the response range of AP between the MI-VS and MI-NT
      groups did not reach statistical significance (40.7 +/- 6.2 vs. 26.4 +/- 3.5
      mmHg). In conclusion, the 6-wk VS treatment significantly improved the baroreflex
      control of SNA, but the effect was limited for the baroreflex total-loop function
      due to the lack of significant improvement in the AP response to percent SNA. 

PMID- 24674860
TI  - Exercise training protects against an acute inflammatory insult in mouse
      epididymal adipose tissue.
AB  - Exercise training reduces systemic and adipose tissue inflammation. However,
      these beneficial effects seem to be largely tied to reductions in adipose tissue
      mass. The purpose of the present study was to determine if exercise training
      confers a protective effect against an acute inflammatory challenge. We
      hypothesized that the induction of inflammatory markers, such as interleukin 6
      (IL-6), suppressor of cytokine signaling 3 (SOCS3), and TNF-alpha by the beta-3
      adrenergic agonist CL 316,243 would be reduced in adipose tissue from trained
      mice and this would be associated with reductions in transient receptor potential
      cation channel 4 (TRPV4), a protein recently shown to regulate the expression of
      proinflammatory cytokines. Exercise training (4 wk of treadmill running, 1 h/day,
      5 days/wk) increased markers of skeletal muscle mitochondrial content and the
      induction of PPAR-gamma coactivator 1 alpha in epididymal adipose tissue. The
      mRNA expression of IL-6, SOCS3, and TNFalpha were not different in subcutaneous
      and epididymal adipose tissue from sedentary and trained mice; however, the CL
      316,243-mediated induction of these genes was attenuated ~50% in epididymal
      adipose tissue from trained mice as were increases in plasma IL-6. The effects of
      training were not explained by reductions in lipolytic responsiveness, but were
      associated with decreases in TRPV4 protein content. These results highlight a
      previously unappreciated anti-inflammatory effect of exercise training on adipose
      tissue immunometabolism and underscores the value of assessing adipose tissue
      inflammation in the presence of an inflammatory insult. 

PMID- 24674861
TI  - Wide-pulse-high-frequency neuromuscular stimulation of triceps surae induces
      greater muscle fatigue compared with conventional stimulation.
AB  - We compared the extent and origin of muscle fatigue induced by short-pulse-low
      frequency [conventional (CONV)] and wide-pulse-high-frequency (WPHF)
      neuromuscular electrical stimulation. We expected CONV contractions to mainly
      originate from depolarization of axonal terminal branches (spatially determined
      muscle fiber recruitment) and WPHF contractions to be partly produced via a
      central pathway (motor unit recruitment according to size principle). Greater
      neuromuscular fatigue was, therefore, expected following CONV compared with WPHF.
      Fourteen healthy subjects underwent 20 WPHF (1 ms-100 Hz) and CONV (50 MUs-25 Hz)
      evoked isometric triceps surae contractions (work/rest periods 20:40 s) at an
      initial target of 10% of maximal voluntary contraction (MVC) force. Force-time
      integral of the 20 evoked contractions (FTI) was used as main index of muscle
      fatigue; MVC force loss was also quantified. Central and peripheral fatigue were
      assessed by voluntary activation level and paired stimulation amplitudes,
      respectively. FTI in WPHF was significantly lower than in CONV (21,717 +/- 11,541
      vs. 37,958 +/- 9,898 N.s P<0,001). The reductions in MVC force (WPHF: -7.0 +/-
      2.7%; CONV: -6.2 +/- 2.5%; P < 0.01) and paired stimulation amplitude (WPHF: -8.0
      +/- 4.0%; CONV: -7.4 +/- 6.1%; P < 0.001) were similar between conditions,
      whereas no change was observed for voluntary activation level (P > 0.05).
      Overall, our results showed a different motor unit recruitment pattern between
      the two neuromuscular electrical stimulation modalities with a lower FTI
      indicating greater muscle fatigue for WPHF, possibly limiting the presumed
      benefits for rehabilitation programs. 

PMID- 24674862
TI  - The effect of the mGlu5 negative allosteric modulator MTEP and NMDA receptor
      partial agonist D-cycloserine on Pavlovian conditioned fear.
AB  - The metabotropic glutamate receptor 5 (mGlu5) and N-methyl-D-aspartate (NMDA)
      receptor are critical for processes underlying synaptic plasticity, such as long
      term potentiation. mGlu5 signaling increases neuronal excitability and
      potentiates NMDA receptor currents in the amygdala and the hippocampus. The
      present study examined the involvement of mGlu5 in the acquisition and
      consolidation of conditioned fear to a tone and context in mice, and explored the
      functional relationship between mGlu5 and NMDA receptors in this regard.
      Experiment 1 showed that systemic administration of the mGlu5 negative allosteric
      modulator 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) prior to
      conditioning significantly attenuated cue-elicited freezing during fear
      conditioning, which suggests that mGlu5 is necessary for the formation of a tone
      shock association. This effect was dose-related (Experiment 2) and not due to any
      effects of MTEP on shock sensitivity or state-dependency (Experiment 3). Post
      conditioning injection of MTEP had no effects (Experiment 4). Although post
      conditioning injection of the NMDA receptor partial agonist D-cycloserine (DCS)
      alone facilitated consolidation of conditioned fear (Experiment 6), it was not
      able to rescue the acquisition deficit caused by MTEP (Experiment 5). Taken
      together, these findings indicate a crucial role for mGlu5 signaling in
      acquisition and NMDA receptor signaling in consolidation of conditioned fear.

PMID- 24674863
TI  - Role of reactive oxygen species in ultra-weak photon emission in biological
      systems.
AB  - Ultra-weak photon emission originates from the relaxation of electronically
      excited species formed in the biological systems such as microorganisms, plants
      and animals including humans. Electronically excited species are formed during
      the oxidative metabolic processes and the oxidative stress reactions that are
      associated with the production of reactive oxygen species (ROS). The review
      attempts to overview experimental evidence on the involvement of superoxide anion
      radical, hydrogen peroxide, hydroxyl radical and singlet oxygen in both the
      spontaneous and the stress-induced ultra-weak photon emission. The oxidation of
      biomolecules comprising either the hydrogen abstraction by superoxide anion and
      hydroxyl radicals or the cycloaddition of singlet oxygen initiate a cascade of
      oxidative reactions that lead to the formation of electronically excited species
      such as triplet excited carbonyl, excited pigments and singlet oxygen. The photon
      emission of these electronically excited species is in the following regions of
      the spectrum (1) triplet excited carbonyl in the near UVA and blue-green areas
      (350-550nm), (2) singlet and triplet excited pigments in the green-red (550
      750nm) and red-near IR (750-1000nm) areas, respectively and (3) singlet oxygen in
      the red (634 and 703nm) and near IR (1270nm) areas. The understanding of the role
      of ROS in photon emission allows us to use the spontaneous and stress-induced
      ultra-weak photon emission as a non-invasive tool for monitoring of the oxidative
      metabolic processes and the oxidative stress reactions in biological systems in
      vivo, respectively.

PMID- 24674864
TI  - Toxicokinetics of novel psychoactive substances: characterization of N
      acetyltransferase (NAT) isoenzymes involved in the phase II metabolism of 2C
      designer drugs.
AB  - The 2,5-dimethoxyphenethylamine-derived designer drugs (so-called "2Cs") recently
      became of great importance on the illicit drug market as stimulating
      hallucinogens. They are distributed and consumed as "novel psychoactive
      substances" (NPS) without any safety testing at the forefront. As previous
      studies have shown, the 2Cs are mainly metabolized by O-demethylation, N
      acetylation, or deamination. Therefore, the aim of this study was to elucidate
      the role of the recombinant human N-acetyltransferase (NAT) isoforms 1 and 2 in
      the phase II metabolism of 2Cs. For these studies, cDNA-expressed recombinant
      human NATs were used and formation of metabolites after incubation was measured
      using GC-MS. NAT2 could be shown to be the only isoform catalyzing the reaction
      in vitro, hence it should be the only relevant enzyme for in vivo acetylation. In
      general, all metabolite formation reactions followed classic Michaelis-Menten
      kinetics and the affinity to human NAT2 was increasing with the volume of the 4
      substituent. In consequence, a slow acetylator phenotype or inhibition of NAT2
      could lead to decreased N-acetylation and might lead to an increased risk of side
      effects caused by these novel psychoactive substances. 

PMID- 24674865
TI  - Metronidazole and amoxicillin susceptibility of Aggregatibacter
      actinomycetemcomitans.

PMID- 24674866
TI  - BCL2, BCL6, IGH, TP53, and MYC protein expression and gene rearrangements as
      prognostic markers in diffuse large B-cell lymphoma: a study of 44 Turkish
      patients.
AB  - The purpose of this study was to determine the frequency of BCL2, BCL6, IGH,
      TP53, and MYC protein expression and rearrangements of the respective genes in
      diffuse large B-cell lymphoma (DLBCL) patients and to assess their prognostic
      values. Samples from 44 patients with DLBCL were evaluated using fluorescence in
      situ hybridization and immunohistochemical analyses. BCL6 was the most rearranged
      gene (63.6%), followed by MYC (31.8%), TP53 (22.7%), and BCL2 (18.2%). Multiple
      rearrangements were detected in 40.9% of the cases. BCL6 was the most expressed
      protein (78.6%), followed by TP53 (69.04%), BCL2 (59.5%) and MYC (14.3%).
      Expression of multiple proteins was detected in 67.4% of the cases. BCL2 (P =
      .003) expression had a significant negative influence on overall survival,whereas
      BCL6 (P = .014) expression had a significant positive influence. Our results with
      a different pattern of gene rearrangements and associated protein overexpression
      indicate the molecular genetic complexity of DLBCLs, which reflects the
      morphologic, biologic, and clinical heterogeneity of these lymphomas. 

PMID- 24674867
TI  - Conversion of channelrhodopsin into a light-gated chloride channel.
AB  - The field of optogenetics uses channelrhodopsins (ChRs) for light-induced
      neuronal activation. However, optimized tools for cellular inhibition at moderate
      light levels are lacking. We found that replacement of E90 in the central gate of
      ChR with positively charged residues produces chloride-conducting ChRs (ChloCs)
      with only negligible cation conductance. Molecular dynamics modeling unveiled
      that a high-affinity Cl(-)-binding site had been generated near the gate.
      Stabilizing the open state dramatically increased the operational light
      sensitivity of expressing cells (slow ChloC). In CA1 pyramidal cells, ChloCs
      completely inhibited action potentials triggered by depolarizing current
      injections or synaptic stimulation. Thus, by inverting the charge of the
      selectivity filter, we have created a class of directly light-gated anion
      channels that can be used to block neuronal output in a fully reversible fashion.

PMID- 24674869
TI  - Discovery of brainwide neural-behavioral maps via multiscale unsupervised
      structure learning.
AB  - A single nervous system can generate many distinct motor patterns. Identifying
      which neurons and circuits control which behaviors has been a laborious piecemeal
      process, usually for one observer-defined behavior at a time. We present a
      fundamentally different approach to neuron-behavior mapping. We optogenetically
      activated 1054 identified neuron lines in Drosophila larvae and tracked the
      behavioral responses from 37,780 animals. Application of multiscale unsupervised
      structure learning methods to the behavioral data enabled us to identify 29
      discrete, statistically distinguishable, observer-unbiased behavioral phenotypes.
      Mapping the neural lines to the behavior(s) they evoke provides a behavioral
      reference atlas for neuron subsets covering a large fraction of larval neurons.
      This atlas is a starting point for connectivity- and activity-mapping studies to
      further investigate the mechanisms by which neurons mediate diverse behaviors. 

PMID- 24674868
TI  - Total synthesis of a functional designer eukaryotic chromosome.
AB  - Rapid advances in DNA synthesis techniques have made it possible to engineer
      viruses, biochemical pathways and assemble bacterial genomes. Here, we report the
      synthesis of a functional 272,871-base pair designer eukaryotic chromosome,
      synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae
      chromosome III. Changes to synIII include TAG/TAA stop-codon replacements,
      deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent
      mating loci as well as insertion of loxPsym sites to enable genome scrambling.
      SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a
      heterozygous diploid reveals a large increase in a-mater derivatives resulting
      from loss of the MATalpha allele on synIII. The complete design and synthesis of
      synIII establishes S. cerevisiae as the basis for designer eukaryotic genome
      biology.

PMID- 24674870
TI  - Entangled states of more than 40 atoms in an optical fiber cavity.
AB  - Multiparticle entanglement enables quantum simulations, quantum computing, and
      quantum-enhanced metrology. Yet, there are few methods to produce and measure
      such entanglement while maintaining single-qubit resolution as the number of
      qubits is scaled up. Using atom chips and fiber-optical cavities, we have
      developed a method based on nondestructive collective measurement and conditional
      evolution to create symmetric entangled states and perform their tomography. We
      demonstrate creation and analysis of entangled states with mean atom numbers up
      to 41 and experimentally prove multiparticle entanglement. Our method is
      independent of atom number and should allow generalization to other entangled
      states and other physical implementations, including circuit quantum
      electrodynamics. 

PMID- 24674871
TI  - An open-label phase II study evaluating the safety and efficacy of ramucirumab
      combined with mFOLFOX-6 as first-line therapy for metastatic colorectal cancer.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR
      2) are believed to mediate angiogenesis in colorectal cancer (CRC). Ramucirumab
      (RAM; IMC-1121B) is a human IgG1 monoclonal antibody that inhibits VEGF ligand
      binding to VEGFR-2, inhibiting VEGFR-2 activation and signaling. METHODS:
      Patients with metastatic CRC, Eastern Cooperative Oncology Group performance
      status 0-1, and adequate organ function who had not received chemotherapy for
      metastatic disease received RAM and the modified FOLFOX-6 regimen every 2 weeks.
      Endpoints included progression-free survival (PFS), objective response rate,
      overall survival, and safety. The sample size was based on a potentially improved
      median PFS from 8 months to 11 months. RESULTS: Forty-eight patients received
      therapy. Median PFS was 11.5 months (95% confidence interval [CI]: 8.6-13.1
      months). The objective response rate was 58.3% (95% CI: 43.21-72.39). The disease
      control rate (complete or partial response plus stable disease) was 93.8% (95%
      CI: 82.8-98.7). Median overall survival was 20.4 months (95% CI: 18.5-25.1
      months). The most frequent grade 3-4 adverse events included neutropenia (grade
      3: 33.3%; grade 4: 8.3%), hypertension (grade 3: 16.7%), and neuropathy (grade 3:
      12.5%). Two patients died during the study due to myocardial infarction and
      cardiopulmonary arrest. CONCLUSION: RAM may enhance the efficacy of modified
      FOLFOX-6 chemotherapy with an acceptable safety profile in metastatic CRC.

PMID- 24674872
TI  - A phase I study of temsirolimus and bryostatin-1 in patients with metastatic
      renal cell carcinoma and soft tissue sarcoma.
AB  - BACKGROUND: Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR)
      complex 1, is approved for the treatment of metastatic renal cell carcinoma
      (RCC). Bryostatin-1 inhibits protein kinase C, a downstream effector of mTOR
      complex 2. We observed antitumor effects with the combination of temsirolimus and
      bryostatin-1 in RCC cell lines. METHODS. Four cohorts of patients received weekly
      bryostatin-1 (20 MUg/m2) with temsirolimus (10, 15, 25, or 37.5 mg) in 28-day
      cycles. RESULTS: Thirty patients received a total of 138 cycles across four dose
      levels. Twenty-five patients had RCC (17 clear cell, 7 papillary, and 1
      unclassified). Two sarcoma patients with prior cytotoxic therapy experienced dose
      limiting toxicity at 15 mg of temsirolimus (grade 3 neutropenia and grade 3
      hypophosphatemia). Subsequently, patients with prior cytotoxic therapy were
      excluded. Two additional dose-limiting toxicities were noted with 37.5 mg of
      temsirolimus (grade 3 neutropenia and grade 3 creatinine elevation).
      Consequently, the maximum tolerated dose was defined as temsirolimus at 25 mg and
      bryostatin-1 at 20 MUg/m2 every 28 days. Of the 25 RCC patients, 3 patients had
      partial responses that lasted for 14 months, 28 months, and >= 80 months,
      respectively. Partial responses were seen in both clear cell and papillary
      histology. CONCLUSION: This combination of 37.5 mg of temsirolimus with 20 MUg/m2
      of bryostatin-1 was reasonably safe and well tolerated. Durable responses were
      observed in 3 of 25 patients with RCC.

PMID- 24674873
TI  - Bosutinib in combination with the aromatase inhibitor exemestane: a phase II
      trial in postmenopausal women with previously treated locally advanced or
      metastatic hormone receptor-positive/HER2-negative breast cancer.
AB  - BACKGROUND: Bosutinib is an oral, selective Src/Abl tyrosine kinase inhibitor
      with activity in breast cancer (BC). We evaluated bosutinib plus exemestane as
      second-line therapy in previously treated hormone receptor-positive (HR+) locally
      advanced or metastatic BC. METHODS: This was a phase II study with patients
      enrolled in a single-arm safety lead-in phase. Patients receiving bosutinib at
      400 mg or 300 mg/day (based on toxicity) plus exemestane at 25 mg/day were
      monitored for adverse events (AEs) and dose-limiting toxicities for 28 days, and
      initial efficacy was assessed. After the lead-in and dose-determination phase,
      randomized evaluation of combination therapy versus exemestane was planned.
      RESULTS: Thirty-nine of 42 patients (93%) experienced treatment-related AEs
      including diarrhea in 28 (67%) and hepatotoxicity in 11 (26%); overall serious
      treatment-related AEs were recorded in 4 (10%). No liver toxicity met Hy's law
      criteria. Dose-limiting toxicities occurred in 5 of 13 patients receiving 400 mg
      (38%) and 3 of 26 patients receiving 300 mg (12%) of bosutinib; all resolved on
      treatment discontinuation. One patient (300 mg/day) achieved confirmed partial
      response; three (400 mg/day, n = 2; 300 mg/day, n = 1) maintained stable disease
      for >24 weeks; a best response of progressive disease occurred in 15 of 42
      patients (36%). Median progression-free survival was 12.3 weeks (80% confidence
      interval: 11.0-15.6). CONCLUSION: The risk-benefit profile of bosutinib at 300
      mg/day plus exemestane resulted in early study termination before the randomized
      portion. Alternative bosutinib regimens merit investigation in BC.

PMID- 24674874
TI  - Bosutinib in combination with the aromatase inhibitor letrozole: a phase II trial
      in postmenopausal women evaluating first-line endocrine therapy in locally
      advanced or metastatic hormone receptor-positive/HER2-negative breast cancer.
AB  - BACKGROUND: Endocrine therapy resistance in hormone receptor-positive (HR+)
      breast cancer (BC) may involve crosstalk between HRs and growth factor signaling
      pathways. We evaluated bosutinib, a dual Src/Abl tyrosine kinase inhibitor that
      has previously demonstrated some antitumor activity in BC, plus letrozole as
      first-line endocrine therapy in locally advanced or metastatic HR+/HER2- BC.
      METHODS; Sixteen postmenopausal women were enrolled in a phase II study
      evaluating the safety/efficacy of bosutinib plus letrozole. In the single-arm
      safety/dose-confirming lead-in (part 1), patients received oral bosutinib at 400
      mg/day plus letrozole at 2.5 mg/day; adverse events (AEs) and dose-limiting
      toxicities (DLTs) were monitored, and initial efficacy was assessed. A randomized
      efficacy/safety phase (part 2) was planned to evaluate the combination versus
      letrozole monotherapy. RESULTS: Fifteen of 16 subjects experienced treatment
      related AEs, most commonly diarrhea (69%). Treatment-related hepatotoxicity AEs
      (primarily alanine aminotransferase [ALT] or aspartate aminotransferase [AST]
      elevations) occurred in 6 of 16 patients (38%). Four of 15 evaluable patients
      (27%) experienced a DLT (grade 3/4 ALT/AST elevations, n = 2; grade 3 rash, n =
      1; grade 3 diarrhea or vomiting, n = 1), including 1 Hy's law hepatotoxicity
      case. All DLTs resolved following treatment discontinuation. One patient achieved
      confirmed partial response; one had stable disease for >24 weeks. Study
      termination occurred before part 2. CONCLUSION: The unfavorable risk-benefit
      ratio did not warrant further investigation of bosutinib plus letrozole.

PMID- 24674875
TI  - Phase ib of sorafenib in combination with everolimus in patients with advanced
      solid tumors, selected on the basis of molecular targets.
AB  - BACKGROUND: Molecular alterations of the PI3K and Ras pathways often occur in
      human cancer. In this trial, the pharmacokinetics, toxicity, and activity of two
      drugs inhibiting these pathways-everolimus and sorafenib-were investigated.
      METHODS: Thirteen patients with progressing solid tumors were treated with
      everolimus and sorafenib, according to a 3+3 scheme. Patients were selected on
      the basis of immunohistochemical expression of tumor molecular targets, including
      phospho-AKT, -p70S6K, and -ERK1/2. RESULTS: The daily recommended dose identified
      was 2.5 mg of everolimus and 600 mg of sorafenib. Dose-limiting toxicities
      included grade 3 asthenia and hand-foot skin reaction. No grade 4 adverse events
      were observed. The most frequent grade 3 toxicities were hypophosphatemia
      (30.8%), alanine aminotransferase level increase, asthenia, and anorexia (14%).
      No pharmacokinetic interactions were identified between everolimus and sorafenib.
      Of 12 evaluable patients, we observed 2 partial responses, with greater than 10%
      shrinkage in an additional 5 patients. Objective responses were observed in one
      patient with a thymoma and in one patient with a lung adenocarcinoma. Tumor
      shrinkage that did not qualify as a partial response was seen in an abdominal
      leiomyosarcoma and in adenoid cystic carcinomas. CONCLUSION: The combination of
      everolimus and sorafenib is safe. The tumor activity observed in different tumor
      types could be the result of the combined action of these drugs as well as the
      molecular selection of the treated population. Further research is warranted to
      better investigate drugs simultaneously blocking the PI3K and the Ras pathways
      and to refine patient selection.

PMID- 24674876
TI  - Effects of current-use fungicides and their mixtures on the feeding and survival
      of the key shredder Gammarus fossarum.
AB  - Fungicides are frequently applied in agriculture and are subsequently detected in
      surface waters in total concentrations of up to several tens of micrograms per
      liter. These concentrations imply potential effects on aquatic communities and
      fundamental ecosystem functions such as leaf litter breakdown. In this context,
      the present study investigates sublethal and lethal effects of organic
      (azoxystrobin, carbendazim, cyprodinil, quinoxyfen, and tebuconazole) and
      inorganic (three copper (Cu)-based substances and sulfur) current-use fungicides
      and their mixtures on the key leaf-shredding invertebrate Gammarus fossarum. The
      feeding activity of fungicide-exposed gammarids was quantified as sublethal
      endpoint using a static (organic fungicides; 7 d test duration) or a semi-static
      (inorganic fungicides; 6 d test duration with a water exchange after 3 d)
      approach (n=30). EC50-values of organic fungicides were generally observed at
      concentrations resulting in less than 20% mortality, with the exception of
      carbendazim. With regard to feeding, quinoxyfen was the most toxic organic
      fungicide, followed by cyprodinil, carbendazim, azoxystrobin, and tebuconazole.
      Although all tested organic fungicides have dissimilar (intended) modes of
      action, a mixture experiment revealed a synergistic effect on gammarids' feeding
      at high concentrations when using "independent action" as the reference model
      (~35% deviation between predicted and observed effect). This may be explained by
      the presence of a synergizing azole fungicide (i.e. tebuconazole) in this
      mixture. Furthermore, lethal concentrations of all Cu-based fungicides assessed
      in this study were comparable amongst one another. However, they differed
      markedly in their effective concentrations when using feeding activity as the
      endpoint, with Cu-sulfate being most toxic, followed by Cu-hydroxide and Cu
      octanoate. In contrast, sulfur neither affected survival nor the feeding activity
      of gammarids (up to ~5 mg/L) but reduced Cu-sulfate's toxicity when applied in a
      binary mixture. Sulfur-related metabolic processes which reduce the physiological
      availability of Cu may explain this antagonistic effect. For both fungicide
      mixtures, the present study thus uncovered deviations from the appropriate
      reference model, while ecotoxicological effects were observed at field relevant
      (total) fungicide concentrations. Additionally, for more than half of the tested
      single substances, a potential risk for Gammarus and thus for the ecological
      function mediated by these organisms was evident at concentrations measured in
      agriculturally influenced surface waters. These results suggest that risks to the
      fundamental ecosystem function of leaf litter breakdown posed by fungicides may
      not be adequately considered during the regulation of these compounds, which
      makes further experimental efforts necessary.

PMID- 24674877
TI  - I-V characteristics of short superconducting nanowires with different bias and
      shunt: a dynamic approach.
AB  - We derived the I-V characteristics of short nanowire in a circuit with and
      without resistive and inductive shunt. For this we used numerical calculations in
      the framework of time-dependent Ginzburg-Landau equations with different
      relaxation times for the amplitude and phase dynamics. We also derived the
      dependence of the I-V characteristics on flux in a superconducting quantum
      interference device made of two such weak links. 

PMID- 24674878
TI  - Plant genome engineering in full bloom.
AB  - The recent development of tools for precise editing of user-specified sequences
      is rapidly changing the landscape for plant genetics and biotechnology. It is now
      possible to target mutations and regulatory proteins to specific sites in a
      genome using zinc-finger nucleases (ZFNs), transcription activator-like
      endonucleases (TALENs), or the clustered regularly interspaced short palindromic
      repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Here we provide an
      update of recent developments in CRISPR/Cas9 technology and highlight online
      resources that will help biologists adopt new genome-editing tools. 

PMID- 24674879
TI  - Factors associated with growth patterns from birth to 18 months in a Beninese
      cohort of children.
AB  - The aim of this study was to analyze factors influencing the growth pattern of
      children from birth to 18 months. A longitudinal prospective study was conducted
      in three maternity wards in Southern Benin. Inclusion took place between June
      2007 and July 2008; children were followed-up until 18 months of age. Height-for
      age and weight-for-height Z-scores were computed using the newborn's
      anthropometric measurements taken at delivery, every month up to 6 months and
      then quarterly. Infant and young child feeding (IYCF) practices and malarial
      morbidity were recorded. Gestational age was estimated using the Ballard method;
      William's sex-specific reference curve of birth weight-for-gestational-age was
      used to determine intrauterine growth retardation (IUGR). Analyses were performed
      on 520 children using a linear mixed model. Low birth weight (coef=-0.43;
      p=0.002), IUGR (coef=-0.49; p<0.001), maternal short stature (coef=-0.25;
      p=0.001) and maternal low weight status (coef=-0.19; p=0.006) were significantly
      associated with growth impairment. Only LBW (coef=-0.28; p=0.05) and maternal low
      weight status (coef=-0.23; p=0.004) were associated with wasting. A good IYCF
      score was positively associated with weight gain (coef=0.14; p<0.001) whereas we
      found a paradoxical association with length (coef=-0.18; p<0.001). Malaria
      morbidity was not associated with growth. LBW, IUGR and maternal low weight
      status and height were important determinants of children's growth. These results
      reinforce and justify continuing public health initiatives to fight IUGR and LBW
      and break the intergenerational cycle of malnutrition. 

PMID- 24674880
TI  - Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients
      with breast, lung, pancreas and colon cancer.
AB  - Although cancer-mediated changes in hemostatic proteins unquestionably promote
      hypercoagulation, the effects of neoplasia on fibrinolysis in the circulation are
      less well defined. The goals of the present investigation were to determine if
      plasma obtained from patients with breast, lung, pancreas and colon cancer was
      less or more susceptible to lysis by tissue-type plasminogen activator (tPA)
      compared to plasma obtained from normal individuals. Archived plasma obtained
      from patients with breast (n = 18), colon/pancreas (n = 27) or lung (n = 19) was
      compared to normal individual plasma (n = 30) using a thrombelastographic assay
      that assessed fibrinolytic vulnerability to exogenously added tPA. Plasma samples
      were activated with tissue factor/celite, had tPA added, and had data collected
      until clot lysis occurred. Additional, similar samples had potato
      carboxypeptidase inhibitor added to assess the role played by thrombin
      activatable fibrinolysis inhibitor in cancer-modulated fibrinolysis. Rather than
      inflicting a hypofibrinolytic state, the three groups of cancers demonstrated
      increased vulnerability to tPA (e.g. decreased time to lysis, increased speed of
      lysis, decreased clot lysis time). However, hypercoagulation manifested as
      increased speed of clot formation and strength compensated for enhanced
      fibrinolytic vulnerability, resulting in a clot residence time that was not
      different from normal individual thrombi. In sum, enhanced hypercoagulability
      associated with cancer was in part diminished by enhanced fibrinolytic
      vulnerability to tPA. 

PMID- 24674881
TI  - Testosterone, anastrozole, factor V Leiden heterozygosity and osteonecrosis of
      the jaws.
AB  - Our specific aim is to describe the development of thrombotic osteonecrosis of
      the jaws after testosterone-anastrozole therapy in a 55-year-old white man
      subsequently found to have previously undiagnosed factor V Leiden heterozygosity.
      Before the diagnosis of V Leiden heterozygosity, he was given testosterone gel,
      50 mg/day, and on testosterone, serum testosterone (963 ng/dl) and estradiol were
      high (50 pg/ml). Anastrozole was started, and testosterone was continued. Six
      months later, osteonecrosis of the jaws was diagnosed. Exogenous testosterone is
      aromatized to estradiol and estradiol-induced thrombophilia, when superimposed on
      underlying familial thrombophilia, as in this case, may lead to thrombosis and
      osteonecrosis. We recommend that before giving testosterone, at a minimum,
      screening for the factor V Leiden and G20210A mutations, and factor VIII and XI
      activity be carried out, to avoid unanticipated thrombosis. 

PMID- 24674882
TI  - B cell transcription factors: Potential new therapeutic targets for SLE.
AB  - B cells represent a critical arm of the adaptive immune system, and under normal
      circumstances, provide long lasting immunity to a wide range of pathogens. To
      achieve this, B cells differentiate into specialized subpopulations, which
      perform unique functions in response to antigen. A complex network of
      transcription factors regulates this transition as well as subsequent effector
      functions. Dysregulation of these transcription factors can lead to altered B
      cell biology and potentially autoimmunity. Systemic lupus erythematosus (SLE) is
      a complex autoimmune disease characterized by increased autoantibody production
      and B cell hyper-reactivity. It still remains unclear, however, what factors
      contribute to disease pathogenesis. Recent work has suggested dysregulation of B
      cell transcription factors may play a role in disease onset. Given the prominent
      role B cells play in the pathogenesis of SLE, it is important to have a full
      understanding of what transcription factors regulate B cell development, and how
      dysregulation of some of these transcription factors may contribute to the
      occurrence and/or pathogenesis of SLE. A comprehensive review of where this field
      currently stands, what new potential targets have recently been identified, and
      what functional information is still missing will be discussed.

PMID- 24674883
TI  - Expansion of CCR4+ activated T cells is associated with memory B cell reduction
      in DOCK8-deficient patients.
AB  - Hyper-IgE syndrome (HIES) is a genetic disorder characterized by elevated IgE
      serum levels, mostly due to mutations in STAT3 or DOCK8. Despite clinical
      heterogeneity between the two forms of the disease, clinical manifestations may
      not be conclusive for diagnosis and immunological differences are still unclear.
      Herein, we performed a detailed characterization of the T- and B-cell
      compartments by flow cytometry in seven HIES patients with homozygous DOCK8
      mutations and six patients presenting heterozygous STAT3 mutations. We observed
      that DOCK8-deficient patients showed a marked reduction of naive and recent
      thymic emigrant (RTE) T lymphocytes together with a relative increase of
      activated T cells, most of which co-expressed the chemokine receptor CCR4, a
      marker of Th2 polarization. Moreover, an extreme reduction of memory B cells was
      detected, despite a normal/increased proportion of immunoglobulin-secreting
      cells. These observations indicate that DOCK8-deficient patients display a
      distinctive immunophenotype which is characteristic of this form of HIES.

PMID- 24674884
TI  - Intestinal autophagy activity is essential for host defense against Salmonella
      typhimurium infection in Caenorhabditis elegans.
AB  - Salmonella typhimurium infects both intestinal epithelial cells and macrophages.
      Autophagy is a lysosomal degradation pathway that is present in all eukaryotes.
      Autophagy has been reported to limit the Salmonella replication in Caenorhabditis
      elegans and in mammals. However, it is unknown whether intestinal autophagy
      activity plays a role in host defense against Salmonella infection in C. elegans.
      In this study, we inhibited the autophagy gene bec-1 in different C. elegans
      tissues and examined the survival of these animals following Salmonella
      infection. Here we show that inhibition of the bec-1 gene in the intestine but
      not in other tissues confers susceptibility to Salmonella infection, which is
      consistent with recent studies in mice showing that autophagy is involved in
      clearance of Salmonella in the intestinal epithelial cells. Therefore, the
      intestinal autophagy activity is essential for host defense against Salmonella
      infection from C. elegans to mice, perhaps also in humans. 

PMID- 24674885
TI  - Preclinical characterization of AMG 330, a CD3/CD33-bispecific T-cell-engaging
      antibody with potential for treatment of acute myelogenous leukemia.
AB  - There is high demand for novel therapeutic options for patients with acute
      myelogenous leukemia (AML). One possible approach is the bispecific T-cell
      engaging (BiTE, a registered trademark of Amgen) antibody AMG 330 with dual
      specificity for CD3 and the sialic acid-binding lectin CD33 (SIGLEC-3), which is
      frequently expressed on the surface of AML blasts and leukemic stem cells. AMG
      330 binds with low nanomolar affinity to CD33 and CD3epsilon of both human and
      cynomolgus monkey origin. Eleven human AML cell lines expressing between 14,400
      and 56,700 CD33 molecules per cell were all potently lysed with EC(50) values
      ranging between 0.4 pmol/L and 3 pmol/L (18-149 pg/mL) by previously resting, AMG
      330-redirected T cells. Complete lysis was achieved after 40 hours of incubation.
      In the presence of AML cells, AMG 330 specifically induced expression of CD69 and
      CD25 as well as release of IFN-gamma, TNF, interleukin (IL)-2, IL-10, and IL-6.
      Ex vivo, AMG 330 mediated autologous depletion of CD33-positive cells from
      cynomolgous monkey bone marrow aspirates. Soluble CD33 at concentrations found in
      bone marrow of patients with AML did not significantly affect activities of AMG
      330. Neoexpression of CD33 on newly activated T cells was negligible as it was
      limited to 6% of T cells in only three out of ten human donors tested. Daily
      intravenous administration with as low as 0.002 mg/kg AMG 330 significantly
      prolonged survival of immunodeficient mice adoptively transferred with human MOLM
      13 AML cells and human T cells. AMG 330 warrants further development as a
      potential therapy for AML.

PMID- 24674887
TI  - |B1(+)|-selective excitation pulse design using the Shinnar-Le Roux algorithm.
AB  - A new mathematical treatment and algorithm for the design of |B1(+)|-selective RF
      excitation pulses is presented and validated. The algorithm is based on a rotated
      Shinnar-Le Roux pulse design algorithm, wherein the pulse's frequency modulation
      waveform is directly designed by the algorithm, and its amplitude and sign
      modulation waveform takes the place of the gradient field. A new pulse
      configuration is described that enables excitation of large tip-angle slice
      selective profiles. Experiments were performed to validate the pulses, and
      simulations were performed to characterize the pulses' sensitivity to off
      resonance, and to compare them to adiabatic (BIR-4) pulses. 

PMID- 24674888
TI  - Chirped CPMG for well-logging NMR applications.
AB  - In NMR well-logging, the measurement apparatus typically consists of a permanent
      magnet which is inserted into a bore, and the sample is the rock surrounding the
      borehole. When compared to the conditions of standard NMR experiments, this
      application is thus challenged by relatively weak and invariably inhomogeneous B0
      and B1 fields. Chemical shift information is not generally obtained in these
      measurements. Instead, diffusivity, porosity and permeability information is
      collected from multi-echo decay measurements - most often using a Carr-Purcell
      Meiboom-Gill (CPMG) pulse sequence to enhance the experiment's limited
      sensitivity. In this work, we explore the consequences of replacing the hard
      square pulses used in a typical CPMG sequence with chirped pulses sweeping a
      range of frequencies. The greater bandwidths that for a maximum B1 level can be
      excited by chirped pulses translates into marked expansion of the detection
      volume, and thus significant signal-to-noise improvements when compared to
      standard CPMG acquisitions using hard pulses. This improvement, usually amounting
      to signal enhancements ?3, can be used to reduce the experimental time of NMR
      well-logging measurements, for measuring T2 even when B0 and B1 inhomogenieties
      complicate the measurements, and opening new opportunities in the determination
      of diffusional properties. 

PMID- 24674886
TI  - Preclinical evaluation of the supercritical extract of azadirachta indica (neem)
      leaves in vitro and in vivo on inhibition of prostate cancer tumor growth.
AB  - Azadirachta indica, commonly known as neem, has gained worldwide prominence
      because of its medical properties, namely antitumor, antiviral, anti
      inflammatory, antihyperglycemic, antifungal, and antibacterial activities.
      Despite these promising results, gaps remain in our understanding of the
      molecular mechanism of action of neem compounds and their potential for use in
      clinical trials. We investigated supercritical extract of neem leaves (SENL) for
      the following: molecular targets in vitro, in vivo efficacy to inhibit tumor
      growth, and bioactive compounds that exert antitumor activity. Treatment of LNCaP
      luc2 prostate cancer cells with SENL suppressed dihydrotestosterone-induced
      androgen receptor and prostate-specific antigen levels. SENL inhibited integrin
      beta1, calreticulin, and focal adhesion kinase activation in LNCaP-luc2 and PC3
      prostate cancer cells. Oral administration of SENL significantly reduced LNCaP
      luc2 xenograft tumor growth in mice with the formation of hyalinized fibrous
      tumor tissue, reduction in the prostate-specific antigen, and increase in AKR1C2
      levels. To identify the active anticancer compounds, we fractionated SENL by high
      pressure liquid chromatography and evaluated 16 peaks for cytotoxic activity.
      Four of the 16 peaks exhibited significant cytotoxic activity against prostate
      cancer cells. Mass spectrometry of the isolated peaks suggested the compounds
      with cytotoxic activity were nimbandiol, nimbolide, 2',3'-dihydronimbolide, and
      28-deoxonimbolide. Analysis of tumor tissue and plasma samples from mice treated
      with SENL indicated 28-deoxonimbolide and nimbolide as the bioactive compounds.
      Overall, our data revealed the bioactive compounds in SENL and suggested that the
      anticancer activity could be mediated through alteration in androgen receptor and
      calreticulin levels in prostate cancer.

PMID- 24674889
TI  - Smokers' rights group challenges New York City's ban on e-cigarettes.

PMID- 24674890
TI  - A study of National Health Service management of chronic osteoarthritis and low
      back pain.
AB  - AIM: To describe treatment and referral patterns and National Health Service
      resource use in patients with chronic pain associated with low back pain or
      osteoarthritis, from a Primary Care perspective. BACKGROUND: Osteoarthritis and
      low back pain are the two commonest debilitating causes of chronic pain, with
      high health and social costs, and particularly important in primary care.
      Understanding current practice and resource use in their management will inform
      health service and educational requirements and the design and optimisation of
      future care. METHOD: Multi-centre, retrospective, descriptive study of adults
      (?18 years) with chronic pain arising from low back pain or osteoarthritis,
      identified through primary care records. Five general practices in Scotland,
      England (two), Northern Ireland and Wales. All patients with a diagnosis of low
      back pain or osteoarthritis made on or before 01/09/2006 who had received three
      or more prescriptions for pain medication were identified and a sub-sample
      randomly selected then consented to an in-depth review of their medical records
      (n=264). Data on management of chronic pain were collected retrospectively from
      patients' records for three years from diagnosis ('newly diagnosed' patients) or
      for the most recent three years ('established' patients). FINDINGS: Patients
      received a wide variety of pain medications with no overall common prescribing
      pattern. GP visits represented the majority of the resource use and 'newly
      diagnosed' patients were significantly more likely to visit their GP for pain
      management than 'established' patients. Although 'newly diagnosed' patients had
      more referrals outside the GP practice, the number of visits to secondary care
      for pain management was similar for both groups. CONCLUSION: This retrospective
      study confirmed the complexity of managing these causes of chronic pain and the
      associated high resource use. It provides an in-depth picture of prescribing and
      referral patterns and of resource use.

PMID- 24674892
TI  - A review of the value of MRI signs in low back pain.
AB  - Low back pain is a common symptom that can lead to disability and major socio
      professional repercussions. Despite advances in imaging, the etiology of the pain
      often remains unknown. Morphological changes related to normal ageing of the disc
      appear on MR imaging without any symptoms. The potential impact of changes seen
      on imaging, especially MRI, also warrants discussion. The purpose of this work is
      to review the state-of-the-art of this subject, underlining relevant key features
      for routine radiological practice. We will first discuss anterior and posterior
      segments of the spine with a focus on anatomical, physiopathological and
      semiological findings. Secondly we will discuss the diagnostic value of each
      sign. 

PMID- 24674891
TI  - Mcm10 deficiency causes defective-replisome-induced mutagenesis and a dependency
      on error-free postreplicative repair.
AB  - Mcm10 is a multifunctional replication factor with reported roles in origin
      activation, polymerase loading, and replication fork progression. The literature
      supporting these variable roles is controversial, and it has been debated whether
      Mcm10 has an active role in elongation. Here, we provide evidence that the mcm10
      1 allele confers alterations in DNA synthesis that lead to defective-replisome
      induced mutagenesis (DRIM). Specifically, we observed that mcm10-1 cells
      exhibited elevated levels of PCNA ubiquitination and activation of the
      translesion polymerase, pol-zeta. Whereas translesion synthesis had no measurable
      impact on viability, mcm10-1 mutants also engaged in error-free postreplicative
      repair (PRR), and this pathway promoted survival at semi-permissive conditions.
      Replication gaps in mcm10-1 were likely caused by elongation defects, as dbf4-1
      mutants, which are compromised for origin activation did not display any
      hallmarks of replication stress. Furthermore, we demonstrate that deficiencies in
      priming, induced by a pol1-1 mutation, also resulted in DRIM, but not in error
      free PRR. Similar to mcm10-1 mutants, DRIM did not rescue the replication defect
      in pol1-1 cells. Thus, it appears that DRIM is not proficient to fill replication
      gaps in pol1-1 and mcm10-1 mutants. Moreover, the ability to correctly prime
      nascent DNA may be a crucial prerequisite to initiate error-free PRR. 

PMID- 24674893
TI  - Dural ectasia in a child with Larsen syndrome.
AB  - INTRODUCTION: We present a case of an incidental finding of dural ectasia in a
      child diagnosed with Larsen syndrome. Larsen syndrome is a rare inherited
      disorder of connective tissue characterized by facial dysmorphism, congenital
      joint dislocations of the hips, knees and elbows, and deformities of the hands
      and feet. Dural ectasia is as an abnormal expansion of the dural sac surrounding
      the spinal cord and may result in spinal morphologic changes, instability, and
      spontaneous dislocation. To the best of our knowledge, the presence of dural
      ectasia in Larsen syndrome has not previously been reported. CASE STUDY: A 6-year
      old boy diagnosed with Larsen syndrome presented with an upper thoracic curve
      measuring 74 degrees, a right thoracic curve measuring 65 degrees, and
      significant cervicothoracic kyphosis with 50% anterior subluxation of C6 on C7
      and C7 on T1. Advanced imaging studies showed dural ectasia (evidenced by spinal
      canal and dural sac expansion), thinning of pedicles and lamina, and C4 and C6
      pars defects with cervical foramen enlargement. The patient received growing rod
      instrumentation (attached to cervical spine fixation) by a combined
      anterior/posterior surgical approach using intraoperative halo. Complications
      included intraoperative medial breach (fully resolved), wound dehiscence, 2
      instances of bilateral broken rods, and a broken cervical rod. Following 7
      lengthening procedures, the patient underwent definitive fusion. DISCUSSION:
      Surgeons should be aware of the potential for dural ectasia in patients with
      Larsen syndrome. Its presence will cause difficulties in the surgical
      intervention for spinal deformity. Multiple factors must be considered, and
      surgical approach and technique will require modification to avoid complications.
      Although dural ectasia confounds surgical intervention in these patients, surgery
      still appears to outweigh the risks associated with delayed intervention. The
      presence of dural ectasia should not preclude surgical decompression and
      stabilization. This report adds to the body of knowledge on the treatment of
      Larsen syndrome by demonstrating the potential existence of dural ectasia and
      highlights the importance of careful and thorough preoperative evaluation and
      diagnostic imaging.

PMID- 24674894
TI  - The "ischial limb": a landmark on anterior ultrasound scanning used to assess
      reduction in developmental dysplasia of the hip.
AB  - BACKGROUND: Early recognition of failure of reduction during abduction splinting
      in developmental dysplasia of the hip (DDH) is essential to avoid inappropriate
      prolonged damaging harness use. Graf ultrasound scanning (USS) is an accepted
      gold standard for assessing neonatal hip dysplasia but cannot verify reduction in
      the abducted position of a neonatal hip in a Pavlik harness. We describe a new
      anatomic landmark of the hip using anterior USS-the "ischial limb," correlate
      this to the position of the femoral head in reduced and dislocated positions, and
      assess the application of this in the assessment of DDH. METHODS: A porcine model
      was used to identify anatomic, radiologic, and ultrasonic features comparable to
      the human neonatal hip. A pilot clinical study was conducted of 50 neonates
      (11M:39F) treated for DDH in Pavlik harness, utilizing weekly anterior USS to
      determine the concentricity of femoral head reduction relative to the ischial
      limb and whether this could identify any failures to achieve reduction. RESULTS:
      The animal model identified an ultrasound landmark, termed the ischial limb that
      represents the ossification zone of the ischial contribution to the tri-radiate
      acetabular cartilage, and approximates to the center of the acetabulum. Anterior
      USS clearly demonstrated this ischial limb in clinical practice and its relation
      to the femoral head in all dysplastic hips (n=79). Immediate concentric reduction
      was observed in 11 patients, more gradual reduction over 3 weeks in 37 patients,
      and failure to achieve stable reduction was verified in 2 patients. The technique
      was reproducible in 100% of patients (n=50). Mean additional clinic time was 5
      minutes per visit. CONCLUSIONS: The ischial limb, identified on anterior hip USS,
      delineates the position of the tri-radiate cartilage. This technique efficiently
      assesses hip reduction during Pavlik harness treatment and can differentiate
      between failure to achieve reduction or maintain a stable reduction at an earlier
      stage than conventional US methods. LEVEL OF EVIDENCE: Development of diagnostic
      criteria on basis of consecutive patients: level 2 evidence.

PMID- 24674895
TI  - Functional connectivity in major depression: increased phase synchronization
      between frontal cortical EEG-source estimates.
AB  - Structural and metabolic alterations in prefrontal brain areas, including the
      subgenual (SGPFC), medial (MPFC) and dorsolateral prefrontal cortex (DLPFC), have
      been shown in major depressive disorder (MDD). Still it remains largely unknown
      how brain connectivity within these regions is altered at the level of neuronal
      oscillations. Therefore, the goal was to analyze prefrontal
      electroencephalographic phase synchronization in MDD and its changes after
      antidepressant treatment. In 60 unmedicated patients and 60 healthy controls
      (HC), a 15-min resting electroencephalogram (EEG) was recorded in subjects at
      baseline and in a subgroup of patients after 2 weeks of antidepressant
      medication. EEG functional connectivity between the SGPFC and the MPFC/DLPFC was
      assessed with eLORETA (low resolution brain electromagnetic tomography) by means
      of lagged phase synchronization. At baseline, patients revealed increased
      prefrontal connectivity at the alpha frequency between the SGPFC and the left
      DLPFC/MPFC. After treatment, an increased connectivity between the SGPFC and the
      right DLPFC/MPFC at the beta frequency was found for MDD. A positive correlation
      was found for baseline beta connectivity and reduction in scores on the Hamilton
      depression rating scale. MDD is characterized by increased EEG functional
      connectivity within frontal brain areas. These EEG markers of disturbed neuronal
      communication might have potential value as biomarkers. 

PMID- 24674896
TI  - Influence of chitosan and carboxymethylchitosan on the polymorphism and
      solubilisation of diflunisal.
AB  - The interactions of diflunisal (DF) with chitosans (CS) of different molecular
      weights and carboxymethylchitosan (CMCS), a water-soluble derivative, have been
      investigated. The interactions in solution have been studied by solubility assays
      in which the highest solubilisation (13-fold) was obtained with CMCS. Solid
      dispersions were prepared by coevaporation and kneading methods. Solid state
      characterisation was performed by X-ray diffraction analysis, scanning electron
      microscopy, thermomicroscopy, differential thermal analysis and infrared
      spectroscopy. Drug-polymer electrostatic interactions and hydrogen bonds are the
      main binding forces in these systems. The kneading method gave rise to amorphous
      systems regardless of the polymer employed. However, coevaporation resulted in
      the formation of different polymorphs of diflunisal (form II or III) depending on
      the type of polymer used. Therefore, it seems that drug-polymer interactions
      determine the crystallization pattern of the drug. Finally, diflunisal release
      from these systems improved markedly with CMCS and significantly in the presence
      of low molecular weight CS. 

PMID- 24674897
TI  - Biomimetic synthesized nanoporous silica@poly(ethyleneimine)s xerogel as drug
      carrier: characteristics and controlled release effect.
AB  - The purpose of this study was to prepare and characterize nanoporous
      silica@poly(ethyleneimine)s (NS@P) xerogel and methanol modified NS@P xerogel
      synthesized with biomimetic method, and investigate controlled release behavior
      of propranolol hydrochloride (PNH) loaded carrier materials in vitro and in vivo.
      Preparation was conducted at ambient conditions, and NS@P xerogel as well as PNH
      loaded NS@P xerogel were characterized using Fourier transform infrared
      spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning
      calorimeter (DSC). Investigations on morphology and porous characteristics of
      NS@P xerogel and methanol modified NS@P xerogel were evaluated with scanning
      electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen
      adsorption. The results showed that the order of morphology compactness was NS@P
      xerogel>25%NS@P xerogel>75%NS@P xerogel because PEIs scaffold ability for silica
      condensation and forming hydrogen bond weakened with increasing volume ratio of
      methanol modification. Moreover, SBET decreased and uniformity of pore size
      distribution was interrupted after methanol modification. PNH loaded carrier
      materials displayed controlled release, and release effect was related with pore
      size of materials and PEIs scaffold ability. In vivo pharmacokinetic study
      demonstrated that release of PNH was delayed due to the PNH incorporated inside
      carrier materials and controlled release effect was in accordance with in vitro
      results. 

PMID- 24674898
TI  - Closure of tracheoesophageal fistula with prefabricated deltopectoral flap.
AB  - Tracheoesophageal fistula (TEF) is a serious complication associated with
      impaired quality of life. However, a successful TEF closure is difficult owing to
      the high incidence of recurrence. We utilized a prefabricated deltopectoral (DP)
      flap for closure of a TEF that occurred after an extended total thyroidectomy.
      Prefabrication of the inner soft tissue lining the DP flap with a split skin
      graft was performed prior to surgical closure of a TEF. Esophageal and tracheal
      mucosa were sutured to the split thickness side and full thickness side of the
      prefabricated DP flap, respectively. A successful closure of the fistula was
      achieved with this procedure. Prefabricated DP flap is a useful procedure for the
      surgical treatment of TEF. 

PMID- 24674899
TI  - Ribonucleotide incorporation by yeast DNA polymerase zeta.
AB  - During replication in yeast, the three B family DNA replicases frequently
      incorporate ribonucleotides (rNMPs) into DNA, and their presence in the nuclear
      genome can affect genome stability. This prompted us to examine ribonucleotide
      incorporation by the fourth B family member, Pol zeta, the enzyme responsible for
      the majority of damage-induced mutagenesis in eukaryotes. We first show that Pol
      zeta inserts rNMPs into DNA and can extend primer termini containing 3'
      ribonucleotides. We then measure rNMP incorporation by Pol zeta in the presence
      of its cofactors, RPA, RFC and PCNA and at normal cellular dNTP and rNTP
      concentrations that exist under unstressed conditions. Under these conditions,
      Pol zeta stably incorporates one rNMP for every 200-300 dNMPs incorporated, a
      frequency that is slightly higher than for the high fidelity replicative DNA
      polymerases. Under damage-induced conditions wherein cellular dNTP concentrations
      are elevated 5-fold, Pol zeta only incorporates one rNMP per 1300 dNMPs.
      Functional interaction of Pol zeta with the mutasome assembly factor Rev1 gives
      comparable rNMP incorporation frequencies. These results suggest that
      ribonucleotide incorporation into DNA during Pol zeta-mediated mutagenesis in
      vivo may be rare.

PMID- 24674900
TI  - Changes in smoking behavior and subsequent mortality risk during a 35-year follow
      up of a cohort in Xi'an, China.
AB  - Prospective evidence of the associations of smoking cessation with chronic
      obstructive pulmonary disease (COPD) and other causes of death in Asia is scarce.
      Previous studies, which were mostly based on baseline smoking behavior only, were
      subject to sick-quitter bias and misclassification resulting from changes in
      smoking behavior during follow-up. We followed up a cohort for 18 years (1976
      1994) to assess changes in smoking behavior and then for an additional 17 years
      (1994-2011) to examine the relationships of continuing to smoke and new quitting
      with mortality risk in 1,494 Chinese people (961 men, 533 women). Of the baseline
      current smokers, 38.7% quit between 1976 and 1994. From 1994 to 2011, a total of
      488 persons (359 men, 129 women) died. Ever smokers had increased risks of lung
      cancer, coronary heart disease, thrombotic stroke, and COPD, with dose-response
      relationships. For all tobacco-related mortality, the relative risk for new
      quitters compared with continuing smokers was 0.68 (95% confidence interval:
      0.46, 0.99) for those who had quit 2-7 years previously and 0.56 (95% confidence
      interval: 0.37, 0.85) for those who had quit 8 years or more previously. The
      corresponding relative risks were 0.69 and 0.45 for lung cancer, 0.78 and 0.51
      for coronary heart disease, 0.76 and 0.84 for thrombotic stroke, and 0.89 and
      0.61 for COPD, respectively. Smoking increased tobacco-related deaths, and
      particularly deaths from COPD, in China, whereas quitting at middle age (at
      approximately 50 years of age) substantially reduced the risks of death from
      these causes. The benefits of smoking cessation were underestimated in previous
      studies that did not use repeated measures. 

PMID- 24674901
TI  - Lam and He respond to "The challenge of tobacco control in China".

PMID- 24674902
TI  - Invited commentary: the challenge of tobacco control in China.
AB  - Smoking cessation is the only way to quickly mitigate the burden of disease and
      the increased risk of death faced by smokers. In this issue of the Journal, He et
      al. (Am J Epidemiol. 2014;179(9):1060-1070) document lower relative risks of
      overall and cause-specific mortality among former smokers compared with
      continuing smokers in a cohort in China. For China, an immediate increase in the
      pace of smoking cessation is essential to avoid a rising burden of smoking
      attributable disease in a country with the world's largest number of smokers.
      These new findings provide nationally relevant evidence of the benefits of
      cessation. Although China is a party to the World Health Organization's Framework
      Convention on Tobacco Control, the government's implementation of tobacco-control
      policies as obligated by the treaty has been limited. China needs to be committed
      to implementing effective measures to promote smoking cessation, a crucial
      element of both the Framework Convention on Tobacco Control and comprehensive
      programs for tobacco control. 

PMID- 24674903
TI  - Improved plasma cholesterol efflux capacity from human macrophages in patients
      with hyperalphalipoproteinemia.
AB  - OBJECTIVES: CETP or HL deficiencies lead to a marked increase in HDL-C levels
      however the atheroprotective effect of this phenotype, in particular the ability
      of HDL particles to remove cholesterol from human macrophages, remains to be
      determined. METHODS: We measured cholesterol efflux from human THP-1 macrophages
      to total plasma or to isolated HDL subfractions in patients with HALP carrying
      molecular defect in either the CETP or LIPC gene. RESULTS: We demonstrate that
      HALP is associated with an increased plasma cholesterol efflux capacity from
      human macrophages. This observation is primarily related to a stimulation of both
      SR-BI and ABCA1 dependent efflux pathways as a result of quantitative elevation
      in HDL2 and enhanced intrinsic capacity of HDL3 subspecies, respectively.
      CONCLUSION: HDL particles from HALP patients with molecular defect within either
      CETP or LIPC gene are not dysfunctional and are efficient to stimulate
      cholesterol efflux from human macrophages.

PMID- 24674904
TI  - Bariatric surgery in morbidly obese patients improves the atherogenic qualitative
      properties of the plasma lipoproteins.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of weight loss
      induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery
      on the atherogenic features of their plasma lipoproteins. METHODS: Twenty-one
      morbidly obese subjects undergoing bariatric surgery were followed up for up to 1
      year after surgery. Plasma and lipoproteins were assayed for chemical composition
      and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size
      was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and
      oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative
      markers. RESULTS: Lipid profile analysis revealed a reduction in the plasma
      concentrations of cholesterol and triglycerides, which were mainly associated
      with a significant reduction in the plasma concentration of circulating apoB
      containing lipoproteins rather than with changes in their relative chemical
      composition. All patients displayed a pattern A phenotype of LDL subfractions and
      a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P <
      0.001). The switch towards predominantly larger HDL particles was due to an
      increase in their relative cholesteryl ester content. Excess weight loss also led
      to a significant decrease in the plasma concentration of oxidised LDL (~-25%; P <
      0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp
      PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound
      Lp-PLA2. CONCLUSION: Our data indicate that the weight loss induced by bariatric
      surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the
      apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL
      2 subfraction.

PMID- 24674905
TI  - Transcriptional responses in Atlantic salmon (Salmo salar) exposed to
      deltamethrin, alone or in combination with azamethiphos.
AB  - Recently, Atlantic salmon (Salmo salar) fish farmers have applied a combination
      of deltamethrin and azamethiphos in high-concentration and short-duration
      immersion treatment to improve protection against sea-lice (Lepeophtheirus sp.).
      In this work we aimed to study the effects of deltamethrin, alone or in
      combination with azamethiphos, on the transcription of stress and detoxification
      marker genes. Atlantic salmon kept at 12 degrees C (one group was also kept at 4
      5 degrees C) were treated with deltamethrin alone or in combination with
      azamethiphos for a total of 40min, and gill and liver tissue harvested for
      transcriptional analysis 2 and 24h post treatment. No lethality was observed
      during the experiment. The result showed that deltamethrin, alone or in
      combination with azamethiphos, affected the transcriptional levels of several
      oxidative stress markers, including MnSOD (SOD2) and HSP70 (HSPA8) in the liver,
      and GPX1, CAT, MnSOD, HSP70 and GSTP1 in the gills. Significant responses for
      CASP3B, BCLX, IGFBP1B and ATP1A1 (Na-K-ATPase a1b) by some of the treatments
      suggest that the pharmaceutical drugs may affect apoptosis, growth and ion
      regulation mechanisms. In fish kept at 4-5 degrees C, different effects were
      observed, suggesting a temperature-dependent response. In conclusion, the
      observed responses indicate that short-term exposure to deltamethrin has a
      profound effect on transcription of the evaluated markers in gills and liver of
      fish. Co-treatment with azamethiphos appears to have small mitigating effects on
      the transcriptional response caused by deltamethrin exposure alone. 

PMID- 24674906
TI  - First experience without pre-ballooning in transapical aortic valve implantation:
      a propensity score-matched analysis.
AB  - OBJECTIVES: Transapical aortic valve implantation (TA-AVI) using the Edwards
      SAPIENTM prosthesis has evolved into a routine procedure for selected high-risk
      elderly patients. The recently introduced SAPIENTM delivery system (Ascendra
      II+TM) with an added nose cone seems to facilitate direct valve implantation
      without prior balloon valvuloplasty (BAV). Here, we report our initial experience
      with this device. METHODS: A total of 128 patients were enrolled in the study in
      2012 and 2013 and were designated Cohort I. For a subset of 79 patients, exact
      cardio- computed tomography-based measurements were available; these patients
      were assigned to Cohort II. All patients received SAPIEN XTTM valves using the TA
      approach. TA-AVI without pre-ballooning was performed in 31.2% (Cohort I) and
      31.6% (Cohort II) of patients. To adjust for baseline variables, propensity score
      (PS)-based pair matching was used. RESULTS: All valves were implanted
      successfully. The use of PS matching resulted in bias reduction for both cohorts.
      For Cohort I, there were no significant differences in the primary end points,
      which were aortic valve incompetence>=2+, Pmean postimplantation, major stroke,
      transient ischaemic attack (TIA), requirement for post-dilatation and necessity
      for new pacemaker implantation. As expected, fluoroscopy time was significantly
      lower in no-BAV patients. In Cohort II, the 30-day TIA rate was lower in the no
      BAV group. CONCLUSIONS: Direct TA implantation of the SAPIEN valve without pre
      ballooning is feasible, safe, does not seem to compromise functional outcomes and
      may be associated with fewer neurological events.

PMID- 24674907
TI  - Delayed therapy with clopidogrel and everolimus prevents progression of
      transplant arteriosclerosis and impairs humoral alloimmunity in murine aortic
      allografts.
AB  - OBJECTIVES: It was previously shown that the combination of clopidogrel and
      everolimus reduced the development of transplant arteriosclerosis. The aim of
      this study was to investigate whether delayed onset of treatment, similar to the
      clinical situation after heart transplantation, inhibits progression of
      transplant arteriosclerosis. METHODS: Fully allogeneic C57BL/6 (H2-b) donor
      aortas were transplanted into CBA.J (H2-k) recipients treated with clopidogrel
      and everolimus alone or in combination starting on Days 1, 7 or 14. Grafts were
      analysed by histology and alloantibodies were detected by fluorescence activated
      cell sorting after transplantation. RESULTS: Delayed platelet inhibition with
      clopidogrel reduced the development of transplant arteriosclerosis [neointima
      formation (Day 14): 50+/-4 vs 84+/-9% (control)]. The combination of clopidogrel
      and everolimus almost abolished formation of transplant arteriosclerosis when
      therapy was started on Day 1 [neointima formation (Day 1): 14+/-5 vs 84+/-9%
      (control)] and also showed a remarkable reduction in both delayed treatment
      groups [neointima formation (Day 7): 24+/-7 vs 84+/-9% (control); neointima
      formation (Day 14): 28+/-11 vs 84+/-9% (control)]. Platelet inhibition alone and
      in combination with everolimus resulted in reduced alloantibody production.
      CONCLUSIONS: These results demonstrate that delayed treatment with clopidogrel
      and everolimus-representative of a clinical setting-prevents the progression of
      transplant arteriosclerosis and impairs humoral immunity in this experimental
      model.

PMID- 24674908
TI  - Hybrid multistep approach to mega-aortic syndrome: the Lupiae technique.
AB  - OBJECTIVES: Several techniques have been described for the treatment of thoraco
      abdominal aneurysms in patients with mega-aortic syndrome (MAS), but the
      incidence of stroke, spinal cord injury and endoleaks remains significant. We
      present the mid-term results of a new hybrid, multistep technique to treat
      patients with MAS. METHODS: From November 2005 to November 2012, 118 patients
      with MAS underwent surgical repair of thoracic and thoraco-abdominal aneurysms
      with the Lupiae technique. Fifty-five patients presented chronic aneurysms and 63
      patients Type A acute dissections. Eighty-three patients underwent ascending
      aorta and arch replacement with a multibranched Dacron graft and epiaortic
      vessels rerouting (thoracic Lupiae procedure). Twenty patients had the thoracic
      Lupiae procedure plus partial visceral debranching (coeliac trunk and superior
      mesenteric artery [SMA]) through an upper mini-laparotomy. Fifteen patients had
      the thoracic Lupiae procedure plus a complete visceral debranching (coeliac
      trunk, SMA and renal arteries) using a second multibranched Dacron graft to
      replace the infrarenal aorta. All the patients with chronic aneurysms and 34 of
      63 patients with Type A dissections underwent implant of endovascular stent
      grafts. RESULTS: In-hospital mortality was 8.4%. No patients had stroke or spinal
      cord injury. The incidence of temporary renal failure was 5.2%. No patients
      presented endoleaks immediately and at follow-up CT scans. No death or
      reoperation occurred during the follow-up. CONCLUSIONS: These results evidence
      that the Lupiae technique is a safe and effective option for the treatment of
      patients with MAS, achieving the complete exclusion of thoraco-abdominal
      aneurysms and of the residual false lumen in patients with acute aortic
      dissections.

PMID- 24674909
TI  - Factors impacting self-perceived readiness for residency training: results of a
      national survey of postgraduate year 1 residents.
AB  - OBJECTIVE: To examine the factors impacting postgraduate year 1 (PGY1) residents'
      self-perceived readiness for residency. METHODS: A total of 1801 residents who
      matched in American Society of Health-System Pharmacists (ASHP)-accredited PGY1
      programs were e-mailed individualized invitations to take an online survey. The
      survey collected self-ratings of readiness for residency training competencies
      including time management and organization, foundational knowledge, clinical
      practice, project management, and communication. KEY FINDINGS: Data from 556
      completed surveys were analyzed. Residents agreed they were ready to perform
      activities requiring time management and organization (median = 4, mean = 4.08),
      foundational knowledge (median = 4, mean = 3.83), clinical practice (median = 4,
      mean = 3.67), and communication (median = 4, mean = 4.05). Residents who
      completed at least 1 academic advance pharmacy practice experience (APPE), 5
      clinical APPEs, or held a bachelors degree felt more confident than their
      counterparts in regard to project management (P < .001, <.001, and .01,
      respectively). CONCLUSION: PGY1 residents generally felt prepared for time
      management and organization, foundational knowledge, and communication residency
      training competencies. This was significant for those who completed 1 or more
      academic APPEs, 5 or more clinical rotations, or a bachelors degree. Study
      results may assist pharmacy schools in preparing students for residency training,
      prospective resident applicants in becoming more competitive candidates for
      residency programs, and residency program directors in resident selection.

PMID- 24674910
TI  - Immunotherapy in Melanoma: Recent Advances and Promising New Therapies.
AB  - The incidence and mortality of melanoma are on the rise. Historically, patients
      diagnosed with metastatic melanoma were faced with a grim prognosis, with
      survival rates of 15% at 5 years. Prior to 2011, no drug or therapeutic regimen
      had been shown to improve overall survival (OS) in metastatic melanoma.
      Chemotherapeutic agents, such as dacarbazine or temozolomide, are often given to
      patients for palliative purposes; high-dose interleukin 2 and biochemotherapy are
      immunotherapeutic options that could be offered to patients with a good
      performance status at specialized centers. Neither has been shown to impact OS,
      but durable complete responses are seen in a minority of patients. Since 2011, 4
      new drugs have been approved by the US Food and Drug Administration for the
      treatment of metastatic melanoma, all of which improve survival. Three of these
      agents (vemurafenib, dabrafenib, and trametinib) are targeted therapies, with
      ipilimumab being the only new immunotherapy. With a focus on immunotherapeutic
      agents, this review seeks to summarize the treatment options currently available
      for metastatic melanoma and to examine those on the near horizon.

PMID- 24674911
TI  - Characterization of lactate utilization and its implication on the physiology of
      Haemophilus influenzae.
AB  - Haemophilus influenzae is a Gram-negative bacillus and a frequent commensal of
      the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l
      lactate metabolism is associated with serum resistance and in vivo survival of
      the organism. To further gain insight into lactate utilization of the non
      typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion
      mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated
      and characterized. It is shown, that the apparent KM of l-lactate uptake is
      20.1MUM as determined for strain Rd KW20. Comparison of the COPD isolate NTHi
      2019-R with the corresponding lctP knockout strain for survival in human serum
      revealed no lactate dependent serum resistance. In contrast, we observed a 4-fold
      attenuation of the mutant strain in a murine model of nasopharyngeal
      colonization. Characterization of lctP transcriptional control shows that the
      lactate utilization system in H. influenzae is not an inductor inducible system.
      Rather negative feedback regulation was observed in the presence of l-lactate and
      this is dependent on the ArcAB regulatory system. Additionally, for 2019 it was
      found that lactate may have signaling function leading to increased cell growth
      in late log phase under conditions where no l-lactate is metabolized. This effect
      seems to be ArcA independent and was not observed in strain Rd KW20. We conclude
      that l-lactate is an important carbon-source and may act as host specific signal
      substrate which fine tunes the globally acting ArcAB regulon and may additionally
      affect a yet unknown signaling system and thus may contribute to enhanced in vivo
      survival. 

PMID- 24674912
TI  - Genetic mechanisms in the intergenerational transmission of health.
AB  - This paper uses a sample of adoptees to study the genetic mechanisms underlying
      intergenerational associations in chronic health conditions. I begin by
      estimating baseline intergenerational models with a sample of approximately
      125,000 parent-child pairs, and find that children with a parent who has a
      specific chronic health condition are at least 100% more likely to have the same
      condition themselves. To assess the role of genetic mechanisms in generating
      these strong correlations, I estimate models using a sample of approximately 2400
      adoptees, and find that genetic transmission accounts for only 20-30% of the
      baseline associations. As falsification tests, I repeat this exercise using
      health measures with externally established levels of genetic determination
      (height and chicken pox), and the results suggest that comparisons of biological
      and adopted children are a valid method of isolating genetic effects in this
      sample. Finally, to corroborate these adoptee-based estimates, I examine health
      correlations among monozygotic twins, which provide an upper bound estimate of
      genetic influences, and find a similarly modest role for genetic transmission. I
      conclude that intergenerational health transmission is an important hindrance to
      overall socioeconomic mobility, but that the majority of transmission occurs
      through environmental factors or gene-environment interactions, leaving scope for
      interventions to effectively mitigate health persistence. 

PMID- 24674913
TI  - Two and three way spectrophotometric-assisted multivariate determination of
      linezolid in the presence of its alkaline and oxidative degradation products and
      application to pharmaceutical formulation.
AB  - Linezolid (LIN) is determined in the presence of its alkaline (ALK) and oxidative
      (OXD) degradation products without preliminary separation based on ultraviolet
      spectrophotometry using two-way chemometric methods; principal component
      regression (PCR) and partial least-squares (PLS), and three-way chemometric
      methods; parallel factor analysis (PARAFAC) and multi-way partial least squares
      (N-PLS). A training set of mixtures containing LIN, ALK and OXD; was prepared in
      the concentration ranges of 12-18, 2.4-3.6 and 1.2-1.8 MUg mL(-1), respectively
      according to a multilevel multifactor experimental design. The multivariate
      calibrations were obtained by measuring the zero-order absorbance from 220 to 320
      nm using the training set. The validation of the multivariate methods was
      realized by analyzing their synthetic mixtures. The capabilities of the
      chemometric analysis methods for the analysis of real samples were evaluated by
      determination of LIN in its pharmaceutical preparation with satisfactory results.
      The accuracy of the methods, evaluated through the root mean square error of
      prediction (RMSEP), was 0.058, 0.026, 0.101 and 0.026 for LIN using PCR, PLS,
      PARAFAC and N-PLS, respectively. Protolytic equilibria of LIN and its degradation
      products were evaluated using the corresponding absorption spectra-pH data
      obtained with PARAFAC. The obtained pKa values of LIN, ALK and OXD are 5.70, 8.90
      and 6.15, respectively. The results obtained were statistically compared to that
      of a reported HPLC method, and there was no significant difference between the
      proposed methods and the reported method regarding both accuracy and precision.

PMID- 24674914
TI  - Spectroscopic and antibacterial studies of new octaazamacrocyclic complexes
      derived from carbohydrazide and isatin.
AB  - A novel series of the macrocyclic complexes of the type: [M(C18H14N10O2)X2],
      where M = Co(II), Ni(II), Cu(II) and Zn(II); X = Cl(-), NO3(-) and CH3COO(-), has
      been synthesized by template condensation of carbohydrazide and isatin in
      methanolic medium. The complexes were characterized by various physico-chemical
      techniques, such as elemental analyses, molar conductance measurements, magnetic
      measurements, and electronic, NMR, IR and EPR spectral studies. The low value of
      molar conductance indicates them to be non-electrolytes. Based on various
      studies, a distorted octahedral geometry was proposed for all the metal
      complexes. Metal complexes were tested for their in vitro antibacterial
      activities against some pathogenic bacterial strains and compared with standard
      antibiotic, Ciprofloxacin. Some of the tested complexes was found effective
      against Gram-positive bacterial strains.

PMID- 24674915
TI  - Mesomorphic, micro-Raman and DFT studies of new calamitic liquid crystals; methyl
      4-[4-(4-alkoxy benzoyloxy)benzylideneamino]benzoates.
AB  - The mesomorphic properties of newly synthesized homologous series of calamitic
      liquid crystals; methyl 4-[4-(4-alkoxy benzoyloxy)benzylideneamino]benzoates,
      H(2n+1)C(n)OC6H4COOC6H4C(H)=N C6H4COOCH3; n = 6, 8, 10, 12, 14, 16 (MABBAB-n)
      containing ester and Schiff base groups as linker have been studied by
      temperature dependent micro-Raman study, differential scanning calorimetry (DSC)
      and polarizing optical microscopy (POM). All members of this series exhibit
      enantiotropic smectic A (SmA) mesophase with oily streak and focal conic
      textures. Analyses of Raman marker bands of phenyl rings, Schiff base and ester
      groups of MABBAB-10 confirm the phase transitions. The Raman study also gives an
      evidence of breaking of weak intermolecular hydrogen bonds associated with ester
      groups and formation of new hydrogen bonds through CN bond at Cr->SmA phase
      transition. The monomer and dimer were optimized and vibrational assignment of
      MABBAB-10 was also done with density functional theoretical (DFT) technique to
      understand the experimental results.

PMID- 24674916
TI  - Biosynthesis of silver nanoparticles using Plectranthus amboinicus leaf extract
      and its antimicrobial activity.
AB  - This study reports the simple green synthesis method for the preparation of
      silver nanoparticles (Ag NPs) using Plectranthus amboinicus leaf extract. The
      pathway of nanoparticles formation is by means of reduction of AgNO3 by leaf
      extract, which acts as both reducing and capping agents. Synthesized Ag NPs were
      subjected to different characterizations for studying the structural, chemical,
      morphological, optical and antimicrobial properties. The bright circular fringes
      in SAED pattern and diffraction peaks in XRD profile reveals high crystalline
      nature of biosynthesized Ag NPs. Morphological studies shows the formation of
      nearly spherical nanoparticles. FTIR spectrum confirms the existence of various
      functional groups of biomolecules capping the nanoparticles. UV-visible spectrum
      displays single SPR band at 428 nm indicating the absence of anisotropic
      particles. The synthesized Ag NPs exhibited better antimicrobial property towards
      gram negative Escherichia coli and towards tested Penicillium spp. than other
      tested microorganisms using disc diffusion method. Finally it has proven that the
      synthesized bio-inspired Ag NPs have potent antimicrobial effect.

PMID- 24674917
TI  - Trapping of muscle relaxant methocarbamol degradation product by complexation
      with copper(II) ion: spectroscopic and quantum chemical studies.
AB  - Structural properties of methocarbamol (Mcm) were extensively studied both
      experimentally and theoretically using FT IR, (1)H NMR, UV-Vis., geometry
      optimization, Mulliken charge, and molecular electrostatic potential. Stability
      arises from hyper-conjugative interactions, charge delocalization and H-bonding
      was analyzed using natural bond orbital (NBO) analysis. Mcm was decomposed in
      ethanol/water mixture at 80 degrees C to guaifenesin [(RS)-3-(2
      methoxyphenoxy)propane-1,2-diol] and carbamate ion [NH2COO(-)], where the
      degradation mechanism was explained by trapping the carbamate ion via the
      complexation with copper(II) ion. The structure of the isolated complex
      ([Cu(NH2COO)2(H2O)]?4H2O) was elucidated by spectral, thermal, and magnetic
      tools. Electronic spectra were discussed by TD-DFT and the descriptions of
      frontier molecular orbitals and the relocations of the electron density were
      determined. Calculated g-tensor values showed best agreement with experimental
      values from EPR when carried out using both the B3LYP and B3PW91 functional. 

PMID- 24674918
TI  - Theoretical study, and infrared and Raman spectra of copper(II) chelated complex
      with dibenzoylmethane.
AB  - There are some discrepancies in both the vibrational assignments and in the metal
      ligand (M-L) bond strengths predicted in the previous studies on the copper (II)
      chelated complex of dibenzoylmethane, Cu(dbm)2. Also, there is a lack of
      theoretical structure, Raman spectrum and full vibrational assignment for
      Cu(dbm)2 in the literatures. Density functional theory (DFT) at the B3LYP level
      and also MP2 calculations using different basis sets, besides Natural Bond
      Orbital (NBO) and Atoms-in-Molecules (AIM) analyses, have been employed to
      investigate the effect of methyl substitution with the phenyl group on the
      stabilities of bis(acetylacetonate) copper (II), Cu(acac)2, and Cu(dbm)2
      complexes and the electron delocalization in their chelated rings. Measured solid
      phase infrared and Raman bands for Cu(dbm)2 complex have been interpreted in
      terms of the calculated vibrational modes and detailed assignment has been
      presented. We concluded that, theoretically, the results of charge transfer
      studies, and experimentally, in-phase symmetric O-Cu-O stretching mode of these
      complexes are very useful measures for M-L bond strength. The electron
      delocalization in the chelated rings and the M-L bond strength in Cu(dbm)2 are
      concluded to be higher than those in Cu(acac)2. The calculated geometries and
      vibrational results are in good agreement with the experimental data.

PMID- 24674919
TI  - Can hospital rounds with pocket ultrasound by cardiologists reduce standard
      echocardiography?
AB  - BACKGROUND: Frequently, hospitalized patients are referred for transthoracic
      echocardiograms. The availability of a pocket mobile echocardiography device that
      can be incorporated on bedside rounds by cardiologists may be a useful and frugal
      alternative. METHODS: This was a cross-sectional study designed to compare the
      accuracy of pocket mobile echocardiography images with those acquired by
      transthoracic echocardiography in a sample of hospitalized patients. Each patient
      referred for echocardiography underwent pocket mobile echocardiography
      acquisition and interpretation by a senior cardiology fellow with level II
      training in echocardiography. Subsequently, transthoracic echocardiography was
      performed by skilled ultrasonographers and interpreted by experienced
      echocardiographers. Both groups were blinded to the results of the alternative
      imaging modality. Visualizability and accuracy for all key echocardiographic
      parameters (ejection fraction, wall motion abnormalities, left ventricular end
      diastolic dimension, inferior vena cava size, aortic and mitral valve pathology,
      and pericardial effusion) were determined and compared between imaging
      modalities. RESULTS: A total of 240 hospitalized patients underwent
      echocardiography with pocket mobile echocardiography and transthoracic
      echocardiography. The mean age was 71 +/- 17 years. Pocket mobile
      echocardiography imaging time was 6.3 +/- 1.5 minutes. Sensitivity of pocket
      mobile echocardiography varied by parameter and was highest for aortic stenosis
      (97%) and lowest for aortic insufficiency (76%). Specificity also varied by
      parameter and was highest for mitral regurgitation (100%) and lowest for left
      ventricular ejection fraction (92%). Equivalence testing revealed the pocket
      mobile echocardiography outcomes to be significantly equivalent to the
      transthoracic echocardiography outcomes with no discernible differences in image
      quality between pocket mobile echocardiography and transthoracic echocardiography
      (P = 7.22 * 10(-7)). All outcomes remain significant after correcting for
      multiple testing using the false discovery rate. CONCLUSIONS: The results from
      rapid bedside pocket mobile echocardiography examinations performed by
      experienced cardiology fellows compared favorably with those from formal
      transthoracic echocardiography studies. For hospitalized patients, this finding
      could shift the burden of performing and interpreting the echocardiogram to the
      examining physician and reduce the number and cost associated with formal
      echocardiography studies.

PMID- 24674920
TI  - From nodeless clouds and vortices to gray ring solitons and symmetry-broken
      states in two-dimensional polariton condensates.
AB  - We consider the existence, stability and dynamics of the nodeless state and
      fundamental nonlinear excitations, such as vortices, for a quasi-two-dimensional
      polariton condensate in the presence of pumping and nonlinear damping. We find a
      series of interesting features that can be directly contrasted to the case of the
      typically energy-conserving ultracold alkali-atom Bose-Einstein condensates
      (BECs). For sizeable parameter ranges, in line with earlier findings, the
      nodeless state becomes unstable towards the formation of stable nonlinear single
      or multi-vortex excitations. The potential instability of the single vortex is
      also examined and is found to possess similar characteristics to those of the
      nodeless cloud. We also report that, contrary to what is known, e.g., for the
      atomic BEC case, stable stationary gray ring solitons (that can be thought of as
      radial forms of Nozaki-Bekki holes) can be found for polariton condensates in
      suitable parametric regimes. In other regimes, however, these may also suffer
      symmetry-breaking instabilities. The dynamical, pattern-forming implications of
      the above instabilities are explored through direct numerical simulations and, in
      turn, give rise to waveforms with triangular or quadrupolar symmetry. 

PMID- 24674921
TI  - OsATG7 is required for autophagy-dependent lipid metabolism in rice postmeiotic
      anther development.
AB  - In flowering plants, the tapetum, the innermost layer of the anther, provides
      both nutrient and lipid components to developing microspores, pollen grains, and
      the pollen coat. Though the programmed cell death of the tapetum is one of the
      most critical and sensitive steps for fertility and is affected by various
      environmental stresses, its regulatory mechanisms remain mostly unknown. Here we
      show that autophagy is required for the metabolic regulation and nutrient supply
      in anthers and that autophagic degradation within tapetum cells is essential for
      postmeiotic anther development in rice. Autophagosome-like structures and several
      vacuole-enclosed lipid bodies were observed in postmeiotic tapetum cells
      specifically at the uninucleate stage during pollen development, which were
      completely abolished in a retrotransposon-insertional OsATG7 (autophagy-related
      7)-knockout mutant defective in autophagy, suggesting that autophagy is induced
      in tapetum cells. Surprisingly, the mutant showed complete sporophytic male
      sterility, failed to accumulate lipidic and starch components in pollen grains at
      the flowering stage, showed reduced pollen germination activity, and had limited
      anther dehiscence. Lipidomic analyses suggested impairment of editing of
      phosphatidylcholines and lipid desaturation in the mutant during pollen
      maturation. These results indicate a critical involvement of autophagy in a
      reproductive developmental process of rice, and shed light on the novel autophagy
      mediated regulation of lipid metabolism in eukaryotic cells.

PMID- 24674922
TI  - The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks
      vascular leak in ovine severe sepsis*.
AB  - OBJECTIVE: To determine if the selective vasopressin type 1a receptor agonist
      selepressin (FE 202158) is as effective as the mixed vasopressin type 1a
      receptor/vasopressin V2 receptor agonist vasopressor hormone arginine vasopressin
      when used as a titrated first-line vasopressor therapy in an ovine model of
      Pseudomonas aeruginosa pneumonia-induced severe sepsis. DESIGN: Prospective,
      randomized, controlled laboratory experiment. SETTING: University animal research
      facility. SUBJECTS: Forty-five chronically instrumented sheep. INTERVENTIONS:
      Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy,
      and P. aeruginosa were instilled into their airways. They were then placed on
      assisted ventilation, awakened, and resuscitated with lactated Ringer's solution
      titrated to maintain hematocrit +/- 3% from baseline levels. If, despite fluid
      management, mean arterial pressure fell by more than 10 mm Hg from baseline
      level, an additional continuous IV infusion of arginine vasopressin or
      selepressin was titrated to raise and maintain mean arterial pressure within no
      less than 10 mm Hg from baseline level. Effects of combination treatment of
      selepressin with the selective vasopressin V2 receptor agonist desmopressin were
      similarly investigated. MEASUREMENTS AND MAIN RESULTS: In septic sheep, MAP fell
      by ~30 mm Hg, systemic vascular resistance index decreased by ~50%, and ~7 L of
      fluid were retained over 24 hours; this fluid accumulation was partially reduced
      by arginine vasopressin and almost completely blocked by selepressin; and
      combined infusion of selepressin and desmopressin increased fluid accumulation to
      levels similar to arginine vasopressin treatment. CONCLUSIONS: Resuscitation with
      the selective vasopressin type 1a receptor agonist selepressin blocked vascular
      leak more effectively than the mixed vasopressin type 1a receptor/vasopressin V2
      receptor agonist arginine vasopressin because of its lack of agonist activity at
      the vasopressin V2 receptor.

PMID- 24674923
TI  - Early administration of hydrocortisone replacement after the advent of septic
      shock: impact on survival and immune response*.
AB  - OBJECTIVES: To investigate the impact of early initiation of hydrocortisone
      therapy on the clinical course of septic shock and on cytokine release. DESIGN:
      Prospective study in patients with septic shock treated with low doses of
      hydrocortisone. SETTING: ICUs and general wards. PATIENTS: Over a 2-year period,
      170 patients with septic shock treated with low doses of hydrocortisone were
      enrolled. Blood was sampled from 34 patients for isolation of peripheral blood
      mononuclear cells and cytokine stimulation before and 24 hours after the start of
      hydrocortisone. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After
      quartile analysis, patients were divided into those with early initiation of
      hydrocortisone (< 9 hr after vasopressors, n = 46) and those with late initiation
      of hydrocortisone (> 9 hr after vasopressors, n = 124). After adjusting for
      disease severity and type of infection, a protective effect of early
      hydrocortisone administration against unfavorable outcome was found (hazard
      ratio, 0.20; p = 0.012). Time of discontinuation of vasopressors was earlier
      among patients with initiation of hydrocortisone within 9 hours. Production of
      tumor necrosis factor-alpha was lower among patients who had had hydrocortisone
      early. CONCLUSIONS: In patients receiving hydrocortisone for septic shock, early
      initiation of treatment was associated with improved survival. This treatment was
      also associated with attenuated stimulation of tumor necrosis factor-alpha.

PMID- 24674924
TI  - Chlorhexidine-impregnated dressing for prevention of catheter-related bloodstream
      infection: a meta-analysis*.
AB  - OBJECTIVE: To assess the efficacy of a chlorhexidine-impregnated dressing for
      prevention of central venous catheter-related colonization and catheter-related
      bloodstream infection using meta-analysis. DATA SOURCES: Multiple computerized
      database searches supplemented by manual searches including relevant conference
      proceedings. STUDY SELECTION: Randomized controlled trials evaluating the
      efficacy of a chlorhexidine-impregnated dressing compared with conventional
      dressings for prevention of catheter colonization and catheter-related
      bloodstream infection. DATA EXTRACTION: Data were extracted on patient and
      catheter characteristics and outcomes. DATA SYNTHESIS: Nine randomized controlled
      trials met the inclusion criteria. Use of a chlorhexidine-impregnated dressing
      resulted in a reduced prevalence of catheter-related bloodstream infection
      (random effects relative risk, 0.60; 95% CI, 0.41-0.88, p = 0.009). The
      prevalence of catheter colonization was also markedly reduced in the
      chlorhexidine-impregnated dressing group (random effects relative risk, 0.52; 95%
      CI, 0.43-0.64; p < 0.001). There was significant benefit for prevention of
      catheter colonization and catheter-related bloodstream infection, including
      arterial catheters used for hemodynamic monitoring. Other than in low birth
      weight infants, adverse effects were rare and minor. CONCLUSIONS: Our analysis
      shows that a chlorhexidine-impregnated dressing is beneficial in preventing
      catheter colonization and, more importantly, catheter-related bloodstream
      infection and warrants routine use in patients at high risk of catheter-related
      bloodstream infection and central venous catheter or arterial catheter
      colonization.

PMID- 24674925
TI  - Outcomes of adult patients with sickle cell disease admitted to the ICU: a case
      series*.
AB  - OBJECTIVE: Sickle cell disease is associated with a decreased life expectancy,
      half of the deaths occurring in the ICU. We aimed to describe the characteristics
      of sickle cell disease patients admitted to ICU and to identify early predictors
      of a complicated outcome, defined as the need for vital support or death. DESIGN:
      Retrospective observational cohort study of sickle cell disease patients over a 6
      year period. SETTING: ICU of a French teaching hospital and sickle cell disease
      referral center. PATIENTS: Hundred thirty-eight ICU admissions in 119 sickle cell
      disease patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU
      admission was mainly indicated for sickle cell disease-related events, especially
      acute chest syndrome. Mechanical ventilation, vasoactive drugs, and renal
      replacement therapy were administered to 25 (18%), 10 (7%), and 10 (7%) episodes,
      respectively. The complicated outcome group (n = 28; 20%) was characterized by a
      more aggressive acute disease within the 48 hours preceding ICU admission, with a
      higher respiratory rate, a more frequent acute kidney injury, and a more
      sustained drop of hemoglobin (all p < 0.01). All nine deaths (7%) were sickle
      cell disease related. None of the sickle cell disease baseline characteristics
      predicted accurately a complicated outcome. In multivariate analysis, hemoglobin
      less than or equal to 7.8 g/dL (odds ratio, 3.6; 95% CI, 1.1-11.9), respiratory
      rate more than or equal to 32 cycles/min (odds ratio, 5.6; 95% CI, 1.8-17.2), and
      acute kidney injury on ICU admission (odds ratio, 11.5; 95% CI, 2.5-52.6) were
      independently associated with a complicated outcome. CONCLUSIONS: Sickle cell
      disease patients are at high risk of complications when admitted to the ICU. A
      sustained drop of hemoglobin, acute respiratory distress, and kidney injury at
      admission are strong predictors of a complicated outcome.

PMID- 24674926
TI  - The impact of variation in renal replacement therapy settings on piperacillin,
      meropenem, and vancomycin drug clearance in the critically ill: an analysis of
      published literature and dosing regimens*.
AB  - OBJECTIVES: To describe the effect of different renal replacement therapy
      modalities and settings on the clearance of meropenem, piperacillin, and
      vancomycin in critically ill patients and to evaluate the frequency with which
      current dosing regimens achieve therapeutic concentrations. DESIGN: Regression
      analyses of published pharmacokinetic data. SETTING: Pubmed was searched for
      relevant articles published between 1952 and 2013. SUBJECTS: Original research
      articles describing the pharmacokinetics of meropenem, piperacillin, and
      vancomycin in critically ill patients receiving renal replacement therapy.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from 30 studies were
      analyzed. The mean age of the patient groups involved in studies of meropenem,
      piperacillin, and vancomycin were 55.3, 60.3, and 56.9 years, respectively. The
      mean blood and effluent flow rates used for each antibiotic were 151.3 and 33.8
      mL/min, 131.8 and 27.3 mL/min, and 189.3 and 35.6 mL/min, respectively, in
      continuous renal replacement therapy studies. Correlations existed between
      effluent flow rate in continuous renal replacement therapy and extracorporeal
      clearance for meropenem (rs = 0.43; p = 0.12), piperacillin (rs = 0.77; p =
      0.10), and vancomycin (rs = 0.90; p = 0.08). Current dosing regimens achieved
      target concentrations for meropenem (89%), piperacillin (83%), and vancomycin
      (60%) against susceptible pathogens. CONCLUSIONS: Effluent flow rate appears to
      be a reliable predictor of antibiotic clearance in critically ill patients
      despite significantly altered pharmacokinetics in these patients. Higher dosing
      regimens maybe required in critically ill patients receiving renal replacement
      therapy, in the presence of high effluent flow rates and/or the presence of
      poorly susceptible pathogens, particularly for vancomycin.

PMID- 24674927
TI  - Association between the choice of IV crystalloid and in-hospital mortality among
      critically ill adults with sepsis*.
AB  - OBJECTIVE: Isotonic saline is the most commonly used crystalloid in the ICU, but
      recent evidence suggests that balanced fluids like Lactated Ringer's solution may
      be preferable. We examined the association between choice of crystalloids and in
      hospital mortality during the resuscitation of critically ill adults with sepsis.
      DESIGN: A retrospective cohort study of patients admitted with sepsis, not
      undergoing any surgical procedures, and treated in an ICU by hospital day 2. We
      used propensity score matching to control for confounding and compared the
      following outcomes after resuscitation with balanced versus with no-balanced
      fluids: in-hospital mortality, acute renal failure with and without dialysis, and
      hospital and ICU lengths of stay. We also estimated the dose-response
      relationship between receipt of increasing proportions of balanced fluids and in
      hospital mortality. SETTING: Three hundred sixty U.S. hospitals that were members
      of the Premier Healthcare alliance between November 2005 and December 2010.
      PATIENTS: A total of 53,448 patients with sepsis, treated with vasopressors and
      crystalloids in an ICU by hospital day 2 including 3,396 (6.4%) that received
      balanced fluids. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients
      treated with balanced fluids were younger and less likely to have heart or
      chronic renal failure, but they were more likely to receive mechanical
      ventilation, invasive monitoring, colloids, steroids, and larger crystalloid
      volumes (median 7 vs 5 L). Among 6,730 patients in a propensity-matched cohort,
      receipt of balanced fluids was associated with lower in-hospital mortality (19.6%
      vs 22.8%; relative risk, 0.86; 95% CI, 0.78, 0.94). Mortality was progressively
      lower among patients receiving larger proportions of balanced fluids. There were
      no significant differences in the prevalence of acute renal failure (with and
      without dialysis) or in-hospital and ICU lengths of stay. CONCLUSIONS: Among
      critically ill adults with sepsis, resuscitation with balanced fluids was
      associated with a lower risk of in-hospital mortality. If confirmed in randomized
      trials, this finding could have significant public health implications, as
      crystalloid resuscitation is nearly universal in sepsis.

PMID- 24674928
TI  - Use of a daily goals checklist for morning ICU rounds: a mixed-methods study.
AB  - OBJECTIVE: To understand the perspectives and attitudes of ICU clinicians about
      use of a daily goals checklist on rounds. DESIGN: Our three data collection
      methods were as follows: (1) Field observations: two investigators conducted
      field observations to understand how and by whom the daily goals checklist was
      used for 80 ICU patient rounds over 6 days. (2) Document analysis: The 72
      completed daily goals checklists from observed rounds were analyzed using mixed
      methods. (3) Interviews: With 56 clinicians, we conducted semistructured
      individual and focus-group interviews, analyzing transcripts using a qualitative
      descriptive approach and content analysis. Triangulation was achieved by a
      multidisciplinary investigative team using two research methods and three data
      sources. SETTING: Fifteen bed closed ICU in a tertiary care, university
      affiliated hospital. PATIENTS: Medical-surgical ICU patients. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Field observations: The daily goals
      checklist was completed for 93% of observed rounds, largely by residents (86%).
      The champion of the verbal review was commonly a resident (83%) or medical
      student (9%). Document analysis: Domains with high completion rates included
      ventilation, sedation, central venous access, nutrition, and various prophylactic
      interventions. Interviews: The daily goals checklist enhanced communication,
      patient care, and education. Nurses, physicians, and pharmacists endorsed its
      enhancement of interdisciplinary communication. It facilitated a structured,
      thorough, and individualized approach to patient care. The daily goals checklist
      helped to identify new patient care issues and sparked management discussions,
      especially for sedation, weaning, and medications. Residents were prominent
      users, finding served as a multipurpose teaching tool. CONCLUSIONS: The daily
      goals checklist was perceived to improve the management of critically ill
      patients by creating a systematic, comprehensive approach to patient care and by
      setting individualized daily goals. Reportedly improving interprofessional
      communication and practice, the daily goals checklist also enhanced patient
      safety and daily progress, encouraging momentum in recovery from critical
      illness. Daily goals checklist review prompted teaching opportunities for
      multidisciplinary learners on morning rounds.

PMID- 24674929
TI  - The association of the BDNF Val66Met polymorphism and the hippocampal volumes in
      healthy humans: a joint meta-analysis of published and new data.
AB  - BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism
      (refSNP Cluster Report: rs6265) is a common and functionally relevant single
      nucleotide polymorphism (SNP). The gene itself, as well as the SNP rs6265, have
      been implicated in hippocampal learning and memory. However, imaging genetic
      studies have produced controversial results about the impact of this SNP on
      hippocampal volumes in healthy subjects. METHODS: We examined the association
      between the rs6265 polymorphism and hippocampal volume in 643 healthy young
      subjects using automatic segmentation and subsequently included these data in a
      meta-analysis based on published studies with 5298 healthy subjects in total.
      RESULTS: We found no significant association between SNP rs6265 and hippocampal
      volumes in our sample (g=0.05, p=0.58). The meta-analysis revealed a small,
      albeit significant difference in hippocampal volumes between genotype groups,
      such that Met-carriers had slightly smaller hippocampal volumes than Val/Val
      homozygotes (g=0.09, p=0.04), an association that was only evident when manual
      (g=0.22, p=0.01) but not automatic tracing approaches (g=0.04, p=0.38) were used.
      Studies using manual tracing showed evidence for publication bias and a
      significant decrease in effect size over the years with increasing sample sizes.
      CONCLUSIONS: This study does not support the association between SNP rs6265 and
      hippocampal volume in healthy individuals. The weakly significant effect observed
      in the meta-analysis is mainly driven by studies with small sample sizes. In
      contrast, our original data and the meta-analysis of automatically segmented
      hippocampal volumes, which was based on studies with large samples sizes,
      revealed no significant genotype effect. Thus, meta-analyses of the association
      between rs6265 and hippocampal volumes should consider possible biases related to
      measuring technique and sample size.

PMID- 24674930
TI  - Transcription profiling of interactions between Lactococcus lactis subsp.
      cremoris SK11 and Lactobacillus paracasei ATCC 334 during Cheddar cheese
      simulation.
AB  - The starter cultures (Lactococcus sp.) and non-starter lactic acid bacteria
      (mostly Lactobacillus spp.) are essential to flavor development of Cheddar
      cheese. The aim of this study was to elucidate the transcriptional interaction
      between Lactococcus lactis subsp. cremoris SK11 and Lactobacillus paracasei ATCC
      334 in mixed cultures during simulated Cheddar cheese manufacture (Pearce
      activity test) and ripening (slurry). Reverse transcription quantitative PCR (RT
      qPCR) was used to quantify the expression of 34 genes common to both bacteria and
      for eight genes specific to either L. lactis subsp. cremoris SK11 or L. paracasei
      ATCC 334. The multifactorial analysis (MFA) performed on fold change results for
      each gene revealed that the genes linked to stress, protein and peptide
      degradation as well as carbohydrate metabolism of L. paracasei ATCC 334 were
      especially overexpressed in mixed culture with L. lactis subsp. cremoris SK11
      during the ripening simulation. For L. lactis subsp. cremoris SK11, genes coding
      for amino acid metabolism were more expressed during the cheese manufacture
      simulation, especially in single culture. These results show how complementary
      functions of starter and NSLAB contribute to activities useful for flavor
      development. 

PMID- 24674931
TI  - [Bone graft reconstruction for posterior mandibular segment using the formwork
      technique].
AB  - INTRODUCTION: Pre-implant bone graft in posterior mandibular segments is
      difficult because of masticatory and lingual mechanical constraints, because of
      the limited bone vascularization, and because of the difficulty to cover it with
      the mucosa. The formwork technique is especially well adapted to this topography.
      TECHNICAL NOTE: The recipient site is abraded with a drill. Grooves are created
      to receive and stabilize the grafts. The bone grafts were harvested from the
      ramus. The thinned cortices are assembled in a formwork and synthesized by mini
      plates. The gaps are filled by bone powder collected during bone harvesting.
      DISCUSSION: The bone volume reconstructed with the formwork technique allows
      anchoring implants more than 8mm long. The proximity of the inferior alveolar
      nerve does not contra indicate this technique. The formwork size and its
      positioning on the alveolar crest can be adapted to prosthetic requirements by
      using osteosynthesis plates. The lateral implant walls are supported by the
      formwork cortices; the implant apex is anchored on the native alveolar crest. The
      primary stability of implants is high, and the torque is important. The ramus
      harvesting decreases operative risks.

PMID- 24674932
TI  - Intra-mandibular adenoid cystic carcinoma.
AB  - Intra-mandibular localization of adenoid cystic carcinoma is rare. This tumor is
      characterized by progressive local, regional, and distant aggressiveness. We
      reviewed the latest data on this rare type of cancer with a small number of
      reported cases, alack of consensus for its treatment, and its bad prognosis. 

PMID- 24674933
TI  - Survey of mycotoxins in corn distillers' dried grains with solubles from seventy
      eight ethanol plants in twelve States in the U.S. In 2011.
AB  - Fuel ethanol co-products known as distillers' dried grains with solubles (DDGS)
      are a significant source of energy, protein, and phosphorous in animal feed. Fuel
      ethanol production may concentrate mycotoxins present in corn into DDGS. One
      hundred and forty one corn DDGS lots collected in 2011 from 78 ethanol plants
      located in 12 states were screened for the mycotoxins deoxynivalenol (DON), 15
      acetyldeoxynivalenol (15-ADON), 3-acetyldeoxynivalenol (3-ADON), nivalenol (NIV),
      and zearalenone (ZON). DON ranged from <0.50 to 14.62 MUg g-1, 15-ADON ranged
      from <0.10 to 7.55 MUg g-1, and ZON ranged from <0.10 to 2.12 MUg g-1. None of
      the DDGS lots contained 3-ADON or NIV. Plants in OH had the highest levels of DON
      overall (mean of 9.51 MUg g-1), and plants in NY, MI, IN, NE, and WI had mean DON
      levels >1 and <4 MUg g-1. Twenty six percent (36/141) of the DDGS lots contained
      1.0 to 5.0 MUg g-1 DON, 2% (3/141) contained >5.0 and <10.0 MUg g-1 DON, and 3%
      (4/141) contained >10.0 MUg g-1 DON. All DDGS lots contaminated with unacceptable
      levels of DON evaded detection prior to their commercial distribution and were
      likely sold as feed products.

PMID- 24674934
TI  - Larvicidal and cytotoxic potential of squamocin on the midgut of Aedes aegypti
      (Diptera: Culicidae).
AB  - Acetogenins are secondary metabolites exclusively produced by Annonaceae, which
      have antitumor, cytotoxic, and pesticide activities. In this study, we evaluated
      the larvicidal and cytotoxic effect of squamocin from Annona squamosa on Aedes
      aegypti (Diptera: Culicidae) midgut. The compound was solubilized in 2% Tween 20
      at 10, 20, 50, 80 and 100 ppm. The assay was conducted in a completely randomized
      design with four replications, each with 20 third-instar larvae. Larval mortality
      was assessed every hour until total mortality, and the data were subjected to
      Probit analysis. Cellular damage was evaluated every 30 min in groups comprising
      five larvae subjected to squamocin at 50 and 100 ppm for 240 min. The total
      larval mortality occurred after 360 min following application of 50, 80, and 100
      ppm squamocin, and 600 min after applying other concentrations with LC50 at 6.4
      ppm. Both 50 and 100 ppm of squamocin showed cytotoxic activity in the midgut
      epithelium of A. aegypti after 240 min with 50 ppm resulting in midgut cells with
      light cytoplasm containing small vacuoles, whereas at 100 ppm were found cells
      with cytoplasm highly vacuolated, damaged apical surface and cell protrusion
      toward the gut lumen. In conclusion, squamocin has the potential to control A.
      aegypti. 

PMID- 24674935
TI  - Analysis of individual and combined effects of ochratoxin A and zearalenone on
      HepG2 and KK-1 cells with mathematical models.
AB  - Ochratoxin A (OTA) and Zearalenone (ZEA) are widespread mycotoxins that
      contaminate foodstuffs simultaneously, but sufficient data regarding their mixed
      toxicities are lacking. This study aims to analyze the style of combined effects
      of OTA and ZEA on cells of their target organs. For this purpose, cytotoxicity
      was determined in HepG2 and KK-1 cells treated with single and combined forms of
      OTA and ZEA. Furthermore, we have analyzed the data using two mathematical models
      based on the concepts of concentration addition (CA) and independent addition
      (IA). By analyzing data with nonlinear regression, toxins applied singly showed
      classic sigmoid dose-response curves in HepG2 cells whereas in KK-1 cells
      hormetic responses were observed. Exposure to equieffective mixtures of OTA and
      ZEA showed additive effects, irrespective of different nonlinear regression
      models used. Our results demonstrate that IA is an appropriate concept to account
      for mixture effects of OTA and ZEA. The results in ROS generation indicate a
      departure from additivity to antagonism or synergism at different concentrations,
      probably due to potential interaction during ROS production. This study shows
      that a risk assessment of mycotoxins should account for mixture effects, and
      prediction models are valuable tools for mixture assessment. 

PMID- 24674936
TI  - Inhibitory effects of respiration inhibitors on aflatoxin production.
AB  - Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic
      fungi, may be used to control aflatoxin without incurring a rapid spread of
      resistant strains. A respiration inhibitor that inhibits aflatoxin production was
      identified during a screening process for natural, aflatoxin-production
      inhibitors. This prompted us to evaluate respiration inhibitors as potential
      aflatoxin control agents. The inhibitory activities of four natural inhibitors,
      seven synthetic miticides, and nine synthetic fungicides were evaluated on
      aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors
      (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin
      production with IC50 values around 10 uM. Among the synthetic miticides,
      pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities
      with IC50 values less than 0.2 uM, whereas cyflumetofen did not show significant
      inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb,
      azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory
      activities, with IC50 values less than 0.5 uM. Fungal growth was not
      significantly affected by any of the inhibitors tested at concentrations used.
      There was no correlation observed between the targets of respiration inhibitors
      (complexes I, II, and III) and their IC50 values for aflatoxin-production
      inhibitory activity. This study suggests that respiration inhibitors, including
      commonly used pesticides, are useful for aflatoxin control.

PMID- 24674937
TI  - Liquid chromatography time of flight mass spectrometry based environmental
      metabolomics for the analysis of Pseudomonas putida Bacteria in potable water.
AB  - Water supply biofilms have the potential to harbour waterborne diseases,
      accelerate corrosion, and contribute to the formation of tuberculation in
      metallic pipes. One particular species of bacteria known to be found in the water
      supply networks is Pseudomonas sp., with the presence of Pseudomonas putida being
      isolated to iron pipe tubercles. Current methods for detecting and analysis pipe
      biofilms are time consuming and expensive. The application of metabolomics
      techniques could provide an alternative method for assessing biofilm risk more
      efficiently based on bacterial activity. As such, this paper investigates the
      application of metabolomic techniques and provides a proof-of-concept application
      using liquid chromatography coupled with time-of-flight mass spectrometry (LC-ToF
      MS) to three biologically independent P. putida samples, across five different
      growth conditions exposed to solid and soluble iron (Fe). Analysis of the samples
      in +ESI and -ESI mode yielded 887 and 1789 metabolite features, respectively.
      Chemometric analysis of the +ESI and -ESI data identified 34 and 39 significant
      metabolite features, respectively, where features were considered significant if
      the fold change was greater than 2 and obtained a p-value less than 0.05.
      Metabolite features were subsequently identified according to the Metabolomics
      Standard Initiative (MSI) Chemical Analysis Workgroup using analytical standards
      and standard online LC-MS databases. Possible markers for P. putida growth, with
      and without being exposed to solid and soluble Fe, were identified from a diverse
      range of different chemical classes of metabolites including nucleobases,
      nucleosides, dipeptides, tripeptides, amino acids, fatty acids, sugars, and
      phospholipids. 

PMID- 24674938
TI  - Clostridium perfringens challenge and dietary fat type affect broiler chicken
      performance and fermentation in the gastrointestinal tract.
AB  - The aim of the present work was to examine how different fats commonly used in
      the feed industry affect broiler performance, nutrient digestibility and
      microbial fermentation in the gastrointestinal tract of broiler chickens
      challenged with virulent Clostridium perfringens strains. Two experiments were
      carried out, each including 480-day-old male broilers (Ross 308), which were
      randomly distributed to eight experimental groups using six replicate pens per
      treatment and 10 birds per pen. In Experiment 1, birds were fed diets containing
      soybean oil, palm kernel fatty acid distillers, rendered pork fat and lard. In
      Experiment 2, birds were fed diets containing rapeseed oil, coconut oil, beef
      tallow and palm oil. In both experiments, the birds were either not challenged or
      challenged with a mixture of three C. perfringens type A strains. Irrespective of
      the fat type present in the diet, C. perfringens did not affect broiler chicken
      body weight gain (BWG) and mortality in either of the two experiments. The BWG
      was affected by dietary fat type in both experiments, indicating that the fatty
      acid composition of the fat source affects broiler growth performance. In
      particular, the inclusion of animal fats tended to improve final BW to a greater
      extent compared with the inclusion of unsaturated vegetable oils. In Experiment
      2, irrespective of the dietary fat type present in the diet, C. perfringens
      challenge significantly impaired feed conversion ratio in the period from 14 to
      28 days (1.63 v. 1.69) and at 42 days (1.65 v. 1.68). In both experiments
      apparent metabolizable energy values were affected by dietary fat type.
      Irrespective of the fat type present in the diet, C. perfringens challenge
      decreased the digesta pH in the crop and ileum, but had no effect in cecal
      contents. Moreover, in Experiment 1, total organic acid concentration in the
      ileum was two to three times lower on soybean oil diets as compared with other
      treatments, indicating that C. perfringens as well as dietary fat type
      significantly affects microbiota activity in the broiler chicken gastrointestinal
      tract. 

PMID- 24674939
TI  - Status epilepticus during early development disrupts sexual behavior in adult
      female rats: recovery with sexual experience.
AB  - Female sexual behavior is sensitive to stress and diseases. Some studies have
      shown that status epilepticus (SE) can affect sexual proceptivity and receptivity
      in female rats and also increases reject responses towards males. However,
      epidemiologic studies indicate that SE is more frequent in young individuals.
      Herein, we assessed the effects of SE in infant females on their sexual behavior
      during adulthood. Thirteen-day-old (P13) rat pups received intraperitoneal
      injections of lithium chloride (3 mEq/kg). Twenty hours later, at P14, SE was
      induced by subcutaneous injection of pilocarpine hydrochloride (100 mg/kg s.c.).
      Control animals were given an equal volume of saline subcutaneously. The animals
      were weaned at P21 and, later in adulthood, were ovariectomized and hormone
      primed with estradiol+progesterone, and their sexual behavior assessed during 4
      separate trials of 30 min each with a stud male. Our results indicate that
      proceptive behaviors (solicitations and hops and darts) were impaired during the
      first trial, but no alterations were observed for receptivity and attractivity.
      By trial 3, all SE females displayed normal proceptivity. These results indicate
      that SE in infancy readily affects proceptivity in a reversible manner. We
      discuss the role of sexual experience in recovery.

PMID- 24674940
TI  - The use of a gas chromatograph coupled to a metal oxide sensor for rapid
      assessment of stool samples from irritable bowel syndrome and inflammatory bowel
      disease patients.
AB  - There is much clinical interest in the development of a low-cost and reliable
      test for diagnosing inflammatory bowel disease (IBD) and irritable bowel syndrome
      (IBS), two very distinct diseases that can present with similar symptoms. The
      assessment of stool samples for the diagnosis of gastro-intestinal diseases is in
      principle an ideal non-invasive testing method. This paper presents an approach
      to stool analysis using headspace gas chromatography and a single metal oxide
      sensor coupled to artificial neural network software. Currently, the system is
      able to distinguish samples from patients with IBS from patients with IBD with a
      sensitivity and specificity of 76% and 88% respectively, with an overall mean
      predictive accuracy of 76%. 

PMID- 24674941
TI  - Validation of the balloon evacuation test: reproducibility and agreement with
      findings from anorectal manometry and electromyography.
AB  - BACKGROUND & AIMS: The balloon evacuation test (BET) measures the time required
      to evacuate a balloon filled with 50 mL water; it has been incorporated into many
      algorithms for diagnosis of pelvic floor dyssynergia. We aimed to assess the
      reproducibility of the BET, determine the upper limit of normal, and assess its
      concordance with evaluation of pelvic floor dyssynergia by anorectal manometry
      (ARM) and pelvic floor surface electromyography (EMG). METHODS: The BET was
      tested in 286 consecutive patients with chronic constipation (mean age, 44 years;
      91% female) before and after 30 days of conservative treatment at a tertiary
      gastroenterology clinic in Italy from March 2010 through May 2012. The BET was
      tested twice, 7 days apart, in 40 healthy individuals (controls: mean age, 38
      years; 92% female). The 238 constipated patients who responded incompletely to
      conservative therapy were examined by ARM, EMG, and digital rectal examination.
      Forty-seven patients with conflicting ARM and BET results underwent defecography.
      RESULTS: The balloon was evacuated within 1 minute by 37 controls (93%; 3
      individuals required 1-2 minutes). Among patients with constipation, 148 (52%)
      passed the balloon within 5 minutes (110 passed the balloon in 1 minute, 35
      passed it in 1-2 minutes, and 3 passed it in 2-5 minutes). The BET showed perfect
      reproducibility in 280 of the patients with constipation (98%) when a time less
      than 2 minutes was set as abnormal. The level of agreement between BET and ARM
      for dyssynergia was 78%, and between BET and EMG it was 83%. Thirty-two patients
      had abnormal results from the BET but normal results from ARM; 31 cases had
      inadequate straining (n = 11) or anatomic defects (n = 20), which could account
      for the abnormal findings from BET. CONCLUSIONS: The BET is reliable for analysis
      of pelvic floor dyssynergia; the optimal upper limit of normal is 2 minutes.
      Findings from the BET have a high level of agreement with those from ARM and EMG.

PMID- 24674943
TI  - Real-life treatment paradigms show infliximab is cost-effective for management of
      ulcerative colitis.
AB  - BACKGROUND & AIMS: Infliximab is effective for induction and maintenance of
      response in patients with moderate to moderately severe ulcerative colitis.
      Previous cost analyses of infliximab treatment for ulcerative colitis used models
      of colectomy vs infliximab and response rates derived from early clinical trials.
      In real life, therapeutic options are more complex; patients frequently choose to
      remain in an unwell state rather than undergo colectomy, and rates of response to
      infliximab are generally higher than those reported from clinical trials. We
      evaluate the real-life cost-effectiveness of infliximab for treatment of
      ulcerative colitis where infliximab was readily available compared with not
      available, causing patients to remain in unwell states. METHODS: We constructed a
      Markov model to simulate disease progression of patients with moderate or
      moderately severe ulcerative colitis who depended on corticosteroids and/or did
      not respond to thiopurine therapy. Utility scores and transition probabilities
      between health states were determined by using data from randomized controlled
      trials and real-life rates published by expert inflammatory bowel disease
      centers. Health care costs were obtained from the Ontario Case Costing Initiative
      and the Alberta Health Schedule of Medical Benefits documents. RESULTS: The
      incremental cost-effectiveness ratios for infliximab treatment of ulcerative
      colitis were $79,000 and $64,000 per quality-adjusted life year, compared with
      ongoing medical therapy, at 5-year and 10-year treatment time horizons,
      respectively. CONCLUSIONS: By using real-life response rates and patients'
      preference to avoid colectomy, infliximab therapy is a cost-effective strategy at
      a willingness-to-pay threshold of $80,000 for treatment of ulcerative colitis.

PMID- 24674942
TI  - Effects of antimicrobial prophylaxis and blood stream infections in patients with
      acute liver failure: a retrospective cohort study.
AB  - BACKGROUND & AIMS: We investigated whether antimicrobial prophylaxis alters the
      incidence of bloodstream infection in patients with acute liver failure (ALF),
      and whether bloodstream infections affect overall mortality within 21 days after
      development of ALF. METHODS: We performed a retrospective cohort analysis of 1551
      patients with ALF enrolled by the US Acute Liver Failure Study Group from January
      1998 through November 2009. We analyzed data on infections in the first 7 days
      after admission and the effects of prophylaxis with antimicrobial drugs on the
      development of bloodstream infections and 21-day mortality. RESULTS: In our study
      population, 600 patients (39%) received antimicrobial prophylaxis and 226
      patients (14.6%) developed at least 1 bloodstream infection. Exposure to
      antimicrobial drugs did not affect the proportion of patients who developed
      bloodstream infections (12.8% in patients with prophylaxis vs 15.7% in
      nonprophylaxed patients; P = .12), but a greater percentage of patients who
      received prophylaxis received liver transplants (28% vs 22%; P = .01). After
      adjusting for confounding factors, overall mortality within 21 days was
      associated independently with age (odds ratio [OR], 1.014), Model for End-stage
      Liver Disease score at admission (OR, 1.078), and vasopressor administration at
      admission (OR, 2.499). Low grade of coma (OR, 0.47) and liver transplantation
      (OR, 0.101) reduced mortality. Although bloodstream infection was associated
      significantly with 21-day mortality (P = .004), an interaction between
      bloodstream infection and etiology was detected: blood stream infection affected
      mortality to a greater extent in nonacetaminophen ALF patients (OR, 2.03) than in
      acetaminophen ALF patients (OR, 1.14). CONCLUSIONS: Based on a large,
      observational study, antimicrobial prophylaxis does not reduce the incidence of
      bloodstream infection or mortality within 21 days of ALF. However, bloodstream
      infections were associated with increased 21-day mortality in patients with ALF
      to a greater extent in patients without than with acetaminophen-associated ALF.
      Our findings do not support the routine use of antimicrobial prophylaxis in
      patients with ALF.

PMID- 24674944
TI  - Herbal medicines for the treatment of functional and inflammatory bowel
      disorders.
AB  - In many parts of the world, there continues to be a long-standing tradition of
      prescribing herbal products for a range of gastrointestinal conditions.
      Scientific evidence supporting the use of all herbal preparations is imperfect,
      however, and available studies are plagued by methodological limitations. For
      functional gastrointestinal disorders, there is limited evidence supporting the
      use of some well-characterized preparations. A number of herbals have
      immunomodulatory activity, and in inflammatory bowel disease there are limited
      positive placebo-controlled trials; other studies used active controls with
      suboptimal doses of the comparators. Like all drugs, herbals can lead to serious
      adverse events (eg, hepatic failure). Quality control is a serious issue to
      consider when prescribing herbal medicines. Many herbal preparations are marketed
      without evidence for stringent adherence to good manufacturing practice
      guidelines. Unpredictable environmental conditions may affect the composition and
      the concentration of the active ingredients of plant extracts. Further,
      commercial herbal products usually combine a variable plethora of chemical
      families with possible medicinal utility. While some of these ingredients might
      be of benefit, the concentration and dose of these constituents needs to be
      closely monitored. Physicians and regulators need to remain very cautious about
      the use of herbal remedies. Appropriate scientific evidence for the claimed
      clinical benefits should become mandatory worldwide, and the standards for
      production and safety monitoring should comply with established standards for
      chemically defined products. If these principles were adopted, the full value of
      herbal remedies may come to light, particularly as the individually bioactive
      compounds present in these preparations become recognized. 

PMID- 24674945
TI  - Return to play after treatment of superior labral tears in professional baseball
      players.
AB  - BACKGROUND: The published return-to-play (RTP) rates for athletes who have
      undergone surgical repair of superior labrum anterior-posterior (SLAP) tears vary
      widely and are generally accepted to be lower in the subset of competitive
      throwers. The efficacy of nonsurgical treatment for this group is unknown.
      HYPOTHESIS: Nonsurgical treatment of SLAP tears in professional baseball players
      leads to RTP before consideration of surgical treatment. Incorporating
      performance statistics and level of competition will result in lower calculated
      RTP rates than have been previously reported. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: A retrospective review of 119 consecutive patients in a
      single professional baseball organization with persistent shoulder pain that
      limited the ability to compete was performed. Sixty-eight patients had magnetic
      resonance imaging-documented SLAP lesions. All patients had failed 1 attempt at
      rehabilitation but had continued with supervised physical therapy. Treatment was
      according to an algorithm focusing on the correction of scapular dyskinesia and
      posterior capsular contracture with glenohumeral internal rotation deficit
      (GIRD), followed by pain-free return to throwing. Those who failed 2 cycles of
      nonsurgical treatment were treated surgically. Success was defined by 2 different
      standards: (1) RTP, in accordance with previous studies; and (2) a more stringent
      standard of return to the same level/quality of professional competition (A, AA,
      AAA, etc) with the incorporation of a return to preinjury individual performance
      statistics (earned run average, walks plus hits per inning pitched), termed
      "return to prior performance" (RPP). RESULTS: Sixty-eight athletes were
      identified with SLAP lesions. Twenty-one pitchers successfully completed the
      nonsurgical algorithm and attempted a return. Their RTP rate was 40%, and their
      RPP rate was 22%. The RTP rate for 27 pitchers who underwent 30 procedures was
      48%, and the RPP rate was 7%. For 10 position players treated nonsurgically, the
      RTP rate was 39%, and the RPP rate was 26%. The RTP rate for 13 position players
      who underwent 15 procedures was 85%, with an RPP rate of 54%. CONCLUSION:
      Nonsurgical treatment correcting scapular dyskinesia and GIRD had a reasonable
      success rate in professional baseball players with painful shoulders and
      documented SLAP lesions. The rate of return after surgical treatment of SLAP
      lesions was low for pitchers. The RTP and RPP rates were higher for position
      players than for pitchers. Nonsurgical treatment should be considered for
      professional baseball players with documented SLAP lesions, as it can lead to
      acceptable RTP and RPP rates.

PMID- 24674946
TI  - First-principles study of band alignments in the p-type hosts BaM2X2 (M = Cu, Ag;
      X = S, Se).
AB  - The electronic structures of four semiconductor compounds BaCu2S2, BaCu2Se2,
      BaAg2S2, and BaAg2Se2 are studied by density functional theory using both semi
      local and hybrid functionals. The ionization energies and electron affinities
      were determined by aligning the electronic states with the vacuum level by
      calculating the electrostatic profile within a supercell slab model. The
      ionization energy and electron affinity of the compounds were calculated using
      the Heyd-Scuseria-Ernzerhof functionals and range from 4.5 eV to 5.4 eV and 3.1
      eV to 3.4 eV, respectively. The replacement of Cu by Ag slightly increases the
      ionization energy and electron affinity, while the replacement of S by Se
      decreases the ionization energy but slightly increases the electron affinity.
      Overall, the low ionization energies and small electron affinities suggest that
      these compounds possess good p-type doping propensities. The band gaps are
      somewhat small to be ideal candidates for transparent semiconducting behavior;
      however, the replacement of Cu with Ag in the barium sulfide compounds can
      increase the band gap from 1.62 to 2.01 eV. 

PMID- 24674947
TI  - Effect of nigranoic acid on Ca2+ influx and its downstream signal mechanism in
      NGF-differentiated PC12 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis has a long history of use as
      a famous traditional Chinese medicine. The plants of genus Schisandra, especially
      Schisandra neglecta, Schisandra rubriflora, and Schisandra sphaerandra are used
      in the same way as Schisandra chinensis in the folk medicine to treat insomnia,
      fatigue, increasing intelligence, and tranquilizing. Many studies showed that
      lignans were the major active components of Schisandra genus, whereas the
      bioactivity of abundant triterpenoids in Schisandra genus, such as nigranoic acid
      (SBB1, 3,4-secocycloartene triterpenoid), has not been examined yet in
      neuropathology. MATERIALS AND METHODS: After treating with SBB1, intracellular
      Ca(2+) concentration was analyzed by Ca(2+) fluorescent indicator (Fluo-4 AM) in
      NGF-differentiated PC12 cells. Intracellular nitric oxide (NO) level was analyzed
      using NO fluorescent indicator (DAF-FM). The expression of extracellular signal
      regulated kinase 1 and 2 (ERK1/2) was analyzed by western blotting, and the
      temporal mRNA for BDNF and c-fos was analyzed using reverse transcription
      quantitative PCR. RESULT: We found that SBB1 induced Ca(2+) influx in a time- and
      concentration-dependent manner, which was significantly attenuated in Ca(2+) free
      media. SBB1 promoted the intracellular NO production which depended on increasing
      cytoplasmic Ca(2+) level. Moreover, SBB1 stimulated activation of ERK1/2 through
      Ca(2+)-CaMKII pathway. In addition, we found that SBB1 increased the expression
      of BDNF and c-fos mRNA. CONCLUSION: These results suggest that SBB1 is able to
      promote NO production and stimulate phosphorylation of ERK1/2 through Ca(2+)
      influx, further impact expression of BDNF and c-fos, which provides evidence for
      the effects of SBB1 that may be benefit to enhance mental and intellectual
      functions.

PMID- 24674948
TI  - An enzyme-coupled assay measuring acetate production for profiling histone
      deacetylase specificity.
AB  - Histone deacetylases catalyze the hydrolysis of an acetyl group from post
      translationally modified acetyl-lysine residues in a wide variety of essential
      cellular proteins, including histones. Because these lysine modifications can
      alter the activity and properties of affected proteins, aberrant
      acetylation/deacetylation may contribute to disease states. Many fundamental
      questions regarding the substrate specificity and regulation of these enzymes
      have yet to be answered. Here, we optimize an enzyme-coupled assay to measure low
      micromolar concentrations of acetate, coupling acetate production to the
      formation of NADH (nicotinamide adenine dinucleotide, reduced form) that is
      measured by changes in either absorbance or fluorescence. Using this assay, we
      measured the steady-state kinetics of peptides representing the H4 histone tail
      and demonstrate that a C-terminally conjugated methylcoumarin enhances the
      catalytic efficiency of deacetylation catalyzed by cobalt(II)-bound histone
      deacetylase 8 [Co(II)-HDAC8] compared with peptide substrates containing a C
      terminal carboxylate, amide, and tryptophan by 50-, 2.8-, and 2.3-fold,
      respectively. This assay can be adapted for a high-throughput screening format to
      identify HDAC substrates and inhibitors. 

PMID- 24674949
TI  - Bridging the gap: strategies to integrate classroom and clinical learning.
AB  - Nursing students often feel their classroom (didactic) learning and clinical
      (practice) experiences are disconnected which can lead to a rejection of academe
      and dissatisfaction with the profession. This classroom/clinical divide may be
      exacerbated because of the increased use of part-time clinical faculty, who are
      often isolated from their didactic peers. If clinical faculty, either novice or
      experienced, are disconnected from didactic faculty, is it any wonder students
      feel their learning is fragmented? The purpose of this paper is to discuss
      strategies to help bridge the gap between didactic and clinical learning.
      Specific integration strategies for faculty are presented using examples from a
      baccalaureate adult nursing didactic course and its related clinical course. The
      role of a clinical coordinator in facilitating course integration and support for
      part-time clinical faculty is described. Ideas for using technology to enhance
      learning and suggestions to promote socialization to decrease faculty isolation
      are also discussed. 

PMID- 24674950
TI  - The evolution of school nursing data indicators in Massachusetts: recommendations
      for a national data set.
AB  - The National Association of School Nurses' research priorities include the
      recommendation that data reliability, quality, and availability be addressed to
      advance research in child and school health. However, identifying a national
      school nursing data set has remained a challenge for school nurses, school
      nursing leaders, school nurse professional organizations, and state school nurse
      consultants. While there is much agreement that school nursing data (with
      associated data integrity) is an incredibly powerful tool for multiple uses, the
      content of a national data set must be developed. In 1993, recognizing the unique
      power of data, Massachusetts began addressing the need for consistent school
      nurse data collection. With more than 20 years' experience--and much
      experimentation, pilot testing, and system modification--Massachusetts is now
      ready to share its data collection system and certain key indicators with other
      states, thus offering a beginning foundation for a national school nursing data
      set.

PMID- 24674951
TI  - Severe Streptococcus pneumoniae 19A pneumonia with empyema in children vaccinated
      with pneumococcal conjugate vaccines.

PMID- 24674952
TI  - Cog-4 has limited diagnostic test accuracy and validity for cognitive assessment
      in stroke survivors.
AB  - BACKGROUND: Guidelines recommend cognitive screening for all stroke survivors but
      do not suggest a preferred tool. Certain elements (orientation, executive
      function, language, and inattention) of the impairment scale, National Institutes
      of Health Stroke Scale (NIHSS), have been suggested as a short cognitive
      screening test-Cog-4. We aimed to describe accuracy and validity of Cog-4 against
      a more detailed cognitive assessment (Montreal Cognitive Assessment [MoCA]).
      METHODS: We assessed consecutive acute stroke unit admissions in 2 hospitals over
      3 months. Four independent blinded assessors performed NIHSS and MoCA between
      days 1 and 4 poststroke. We described test properties of Cog-4 for MoCA-defined
      cognitive impairment using usual thresholds (Cog-4>=1 and MoCA<26 of 30) and
      described the correlations of individual Cog-4 components with broadly equivalent
      MoCA domains. RESULTS: We assessed 173 participants; 166 had Cog-4 data and 148
      MoCA. MoCA described 84% (n=124) of assessed participants as having cognitive
      impairment and the Cog-4, 37% (n=62). Cog-4 had a sensitivity of .36 (95%
      confidence interval [CI]: .28-.45) and a specificity of .96 (95% CI: .80-.99)
      (positive predictive value: .98, negative predictive value: .23) for MoCA-defined
      cognitive impairment. Individual Cog-4 items correlated with certain MoCA
      domains, but the strength of association was modest (r=-.44 orientation, -.37
      language, -.19 for inattention, and no significant correlation for executive
      function, P=.72). CONCLUSIONS: Our data suggest that many stroke survivors with
      MoCA-defined cognitive problems would not be detected by Cog-4. Subtest
      correlations suggest that Cog-4 may not be a valid measure of the cognitive
      domains that it purports to describe. Other brief cognitive screening tests may
      be better suited to acute stroke.

PMID- 24674953
TI  - Eight-and-a-half syndrome: a rare presentation of pontine infarction.
AB  - "Eight-and-a-half" syndrome is "one-and-a-half" syndrome (conjugated horizontal
      gaze palsy and internuclear ophthalmoplegia) plus ipsilateral fascicular cranial
      nerve seventh palsy. This rare condition, particularly when isolated, is caused
      by circumscribed lesions of the pontine tegmentum involving the abducens nucleus,
      the ipsilateral medial longitudinal fasciculus, and the adjacent facial
      colliculus. Its recognition is therefore of considerable diagnostic value. We
      report a case of a 65-year-old man who presented with eight-and-a-half syndrome
      in which brain magnetic resonance imaging scan revealed a lacunar pontine
      infarction. 

PMID- 24674954
TI  - Predicting 10-day mortality in patients with strokes using neural networks and
      multivariate statistical methods.
AB  - BACKGROUND: The aim of the present study was to evaluate the performance of 2
      different multivariate statistical methods and artificial neural networks (ANNs)
      in predicting the mortality of hemorrhagic and ischemic patients within the first
      10 days after stroke. METHODS: The multilayer perceptron (MLP) ANN model and
      multivariate statistical methods (multivariate discriminant analysis [MDA] and
      logistic regression analysis [LRA]) have been used to predict acute stroke
      mortality. The data of total 570 patients (230 hemorrhagic and 340 ischemic
      stroke), who were admitted to the hospital within the first 24 hours after stroke
      onset, have been used to develop prediction models. The factors affecting the
      prognosis were used as inputs for prediction models. Survival or death status of
      the patients was taken as output of the models. RESULTS: For the MLP method, the
      accuracies were 99.9% in a training data set and 80.9% in a testing data set for
      the hemorrhagic group, whereas 97.8% and 75.9% for the ischemic group,
      respectively. For the MDA method, the training and testing performances were
      89.8%, 87.8% and 80.6%, 79.7% for hemorrhagic and ischemic groups, respectively.
      For the LRA method, the training and testing performances for the hemorrhagic
      group were 89.7% and 86.1%, and for the ischemic group were 81.7% and 80.9%,
      respectively. CONCLUSIONS: Training and test performances yielded different
      results for ischemic and hemorrhagic groups. MLP method was most successful for
      the training phase, whereas LRA and MDA methods were successful for the test
      phase. In the hemorrhagic group, higher prediction performances were achieved for
      both training and testing phases.

PMID- 24674955
TI  - Stroke in thrombotic thrombocytopenic purpura induced by thyrotoxicosis: a case
      report.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a hematologic disease involving the
      platelet aggregation and resulting in hemolytic anemia, thrombocytopenia, and
      microvascular occlusion. Although frequent neurologic features are headache and
      confusion, focal deficit is described in 30% of the cases. There are a lot of
      causes inducing thrombotic thrombocytopenic, but reports are lacking when
      associated with Grave disease. We describe the case of a 51-year-old Caucasian
      woman presenting a 24-hour story of sudden onset of dysarthria and left superior
      limb palsy. Four months before, she developed severe hyperthyroidism associated
      with petechiae, hemolytic anemia, thrombocytopenia, and schistocytes at blood
      film examination. Relapse of TTP in association with Grave disease was diagnosed.
      There are few reports describing association between Grave disease and TTP with
      only mild neurologic involvement. We described, to our knowledge, the first case
      of acute ischemic stroke secondary to thrombotic thrombocytopenic induced by
      thyrotoxicosis. 

PMID- 24674956
TI  - An unusual cause of blindness: infarction in the bilateral lateral geniculate
      bodies.
AB  - A 10-year-old girl presented with acute blindness after a severe episode of
      febrile diarrhea. Magnetic resonance images were consistent with the diagnosis of
      infarction in the bilateral lateral geniculate bodies. 

PMID- 24674957
TI  - Characterization of Juquitiba virus in Oligoryzomys fornesi from Brazilian
      Cerrado.
AB  - The Juquitiba virus, an agent of Hantavirus Cardiopulmonary Syndrome, is one of
      the most widely distributed hantavirus found in South America. It has been
      detected in Oligoryzomys nigripes, Akodon montensis, Oxymycterus judex, Akodon
      paranaensis in Brazil and in O. nigripes, Oryzomys sp. and Oligoryzomys fornesi
      rodents in Argentine, Paraguay and Uruguay. Here, we report the genomic
      characterization of the complete S segment from the Juquitiba strain, isolated
      from the lung tissues of O. fornesi, the presumed rodent reservoir of Anajatuba
      virus in Brazilian Amazon, captured in the Cerrado Biome, Brazil. 

PMID- 24674958
TI  - A rapid throughput approach identifies cognitive deficits in adult zebrafish from
      developmental exposure to polybrominated flame retardants.
AB  - A substantial body of evidence has correlated the human body burdens of some
      polybrominated diphenyl ether (PBDE) flame retardants with cognitive and other
      behavioral deficits. Adult zebrafish exhibit testable learning and memory, making
      them an increasingly attractive model for neurotoxicology. Our goal was to
      develop a rapid throughput means of identifying the cognitive impact of
      developmental exposure to flame retardants in the zebrafish model. We exposed
      embryos from 6h post fertilization to 5 days post fertilization to either PBDE 47
      (0.1MUM), PBDE 99 (0.1MUM) or PBDE 153 (0.1MUM), vehicle (0.1% DMSO), or embryo
      medium (EM). The larvae were grown to adulthood and evaluated for the rate at
      which they learned an active-avoidance response in an automated shuttle box
      array. Zebrafish developmentally exposed to PBDE 47 learned the active avoidance
      paradigm significantly faster than the 0.1% DMSO control fish (P<0.0001), but
      exhibited significantly poorer performance when retested suggestive of impaired
      memory retention or altered neuromotor activity. Learning in the PBDE 153 group
      was not significantly different from the DMSO group. Developmental exposure to
      0.1% DMSO impaired adult active avoidance learning relative to the sham group
      (n=39; P<0.0001). PBDE 99 prevented the DMSO effect, yielding a learning rate not
      significantly different from the sham group (n=36; P>0.9). Our results underscore
      the importance of vehicle choice in accurately assessing chemical effects on
      behavior. Active avoidance response in zebrafish is an effective model of
      learning that, combined with automated shuttle box testing, will provide a highly
      efficient platform for evaluating persistent neurotoxic hazard from many
      chemicals. 

PMID- 24674960
TI  - Pathologic and imaging correlates of cognitive deficits in multiple sclerosis:
      changing the paradigm of diagnosis and prognosis.
AB  - From 1868, when Charcot first described the clinical features and the pathologic
      correlates, up till the present day, multiple sclerosis (MS) has commonly been
      characterized by the symptoms caused by inflammatory plaques in the white matter
      of the brain and spinal cord. Early use of magnetic resonance imaging (MRI) to
      diagnose MS focused on detecting these white matter lesions. By the 1990s,
      researchers recognized that many patients with MS have cognitive deficits that
      can cause severe disability, and also determined the associated pathology; these
      findings shed more light on both the pathogenesis and progression. Since 2004,
      several lines of evidence have shown that the extent of white matter plaques
      identified on MRI does not correlate well with cognitive deficits. High
      resolution MRI and advances in immunohistochemical techniques have enabled
      detection of cortical demyelination early in the course, correlating with
      cognitive deficits. Late in the course, pathologic changes in normal-looking
      white and gray matter correlate more closely with progressive cognitive deficits
      than with visual, sensory, and motor symptoms. This finding implies the need to
      redefine the disease and its progression. In this review, we discuss the
      histopathologic studies of cortical plaques in MS and early indications about
      their role in disease definition and progression, describe the role of high
      resolution MRI in staging and determining progression of cognitive symptoms, and
      discuss how advances in these areas are forcing us to rethink diagnosis and
      determination of progression. 

PMID- 24674959
TI  - Involvement of autophagy in hypoxic-excitotoxic neuronal death.
AB  - Neuronal autophagy is increased in numerous excitotoxic conditions including
      neonatal cerebral hypoxia-ischemia (HI). However, the role of this HI-induced
      autophagy remains unclear. To clarify this role we established an in vitro model
      of excitotoxicity combining kainate treatment (Ka, 30 uM) with hypoxia (Hx, 6%
      oxygen) in primary neuron cultures. KaHx rapidly induced excitotoxic death that
      was completely prevented by MK801 or EGTA. KaHx also stimulated neuronal
      autophagic flux as shown by a rise in autophagosome number (increased levels of
      LC3-II and punctate LC3 labeling) accompanied by increases in lysosomal abundance
      and activity (increased SQSTM1/p62 degradation, and increased LC3-II levels in
      the presence of lysosomal inhibitors) and fusion (shown using an RFP-GFP-LC3
      reporter). To determine the role of the enhanced autophagy we applied either
      pharmacological autophagy inhibitors (3-methyladenine or pepstatinA/E64) or
      lentiviral vectors delivering shRNAs targeting Becn1 or Atg7. Both strategies
      reduced KaHx-induced neuronal death. A prodeath role of autophagy was also
      confirmed by the enhanced toxicity of KaHx in cultures overexpressing BECN1 or
      ATG7. Finally, in vivo inhibition of autophagy by intrastriatal injection of a
      lentiviral vector expressing a Becn1-targeting shRNA increased the volume of
      intact striatum in a rat model of severe neonatal cerebral HI. These results
      clearly show a death-mediating role of autophagy in hypoxic-excitotoxic
      conditions and suggest that inhibition of autophagy should be considered as a
      neuroprotective strategy in HI brain injuries.

PMID- 24674961
TI  - Memory and executive functions in patients with obsessive-compulsive disorder.
AB  - OBJECTIVE: We investigated whether patients with obsessive-compulsive disorder
      have poorer memory and executive functions than healthy controls. BACKGROUND: The
      relatively inconsistent previous findings on this question reflect a lack of well
      matched control groups, the inclusion of patients with comorbidity, and the use
      of noncomparable neuropsychological tests to assess memory and executive
      functions. METHODS: We used well-accepted neuropsychological tests of memory and
      executive functions to assess 42 patients who had obsessive-compulsive disorder
      without comorbidity, and 42 healthy controls. We matched the patients and
      controls pairwise by sex, age, and years of education. RESULTS: The patients
      performed significantly worse than the controls on the Rey Complex Figure Test,
      which assesses visuospatial memory and organizational skills. This group
      difference remained after we controlled for age, education, intelligence, and
      severity of depressive symptoms. CONCLUSIONS: The findings indicate that patients
      with obsessive-compulsive disorder may have impaired visuospatial memory and
      organizational skills, and these impairments should be considered in treatment.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00792038.

PMID- 24674962
TI  - Biofeedback treatment for Tourette syndrome: a preliminary randomized controlled
      trial.
AB  - OBJECTIVE: To study the clinical effectiveness of biofeedback treatment in
      reducing tics in patients with Tourette syndrome. BACKGROUND: Despite advances in
      the pharmacologic treatment of patients with Tourette syndrome, many remain
      troubled by their tics, which may be resistant to multiple medications at
      tolerable doses. Electrodermal biofeedback is a noninvasive biobehavioral
      intervention that can be useful in managing neuropsychiatric and neurologic
      conditions. METHODS: We conducted a randomized controlled trial of electrodermal
      biofeedback training in 21 patients with Tourette syndrome. RESULTS: After
      training the patients for 3 sessions a week over 4 weeks, we observed a
      significant reduction in tic frequency and improved indices of subjective well
      being in both the active-biofeedback and sham-feedback (control) groups, but
      there was no difference between the groups in these measurements. Furthermore,
      the active-treatment group did not demonstrably learn to reduce their sympathetic
      electrodermal tone using biofeedback. CONCLUSIONS: Our findings indicate that
      this form of biofeedback training was unable to produce a clinical effect greater
      than placebo. The main confounding factor appeared to be the 30-minute duration
      of the training sessions, which made it difficult for patients to sustain a
      reduction in sympathetic tone when their tics themselves were generating
      competing phasic electrodermal arousal responses. Despite a negative finding in
      this study, electrodermal biofeedback training may have a role in managing tics
      if optimal training schedules can be identified.

PMID- 24674963
TI  - Cognitive but not affective theory of mind deficits in mild relapsing-remitting
      multiple sclerosis.
AB  - OBJECTIVE: We studied theory of mind (ToM) in patients with mild relapsing
      remitting multiple sclerosis (MS), seeking possible dissociations between its 2
      components: cognitive ToM (the ability to infer others' intentions) and affective
      ToM (the ability to infer others' emotional states). We analyzed the relationship
      of ToM to executive function, depression, and fatigue. BACKGROUND: Dissociations
      between cognitive and affective ToM have been found in several neurologic and
      neuropsychiatric diseases. Most ToM studies in patients with MS have shown
      general ToM deficits but have not analyzed the cognitive and affective aspects
      individually. METHODS: We used the Faux Pas test of ToM and tests of executive
      function to assess 18 patients with mild relapsing-remitting MS and 16 control
      participants. RESULTS: Our patients showed deficits in cognitive ToM, but their
      affective ToM seemed to be spared. Their cognitive ToM deficits were not related
      to executive dysfunction, depression, or fatigue. CONCLUSIONS: Our study is the
      first differential analysis showing cognitive but not affective ToM deficits in
      mild relapsing-remitting MS. Further research is needed to determine the exact
      nature and the real impact of these deficits, and to establish their relationship
      with the neuropathology and progression of MS.

PMID- 24674964
TI  - Peripheral dysgraphia: dissociations of lowercase from uppercase letters and of
      print from cursive writing.
AB  - Clinical analyses of patients with acquired dysgraphia provide unique
      opportunities to understand the cognitive and neural organization of written
      language production. We report J.B., a 50-year-old woman with peripheral
      dysgraphia who had prominent dissociations in her ability to write in lowercase
      versus uppercase and print versus cursive. We gave J.B. a series of tasks that
      evaluated her skills at writing uppercase and lowercase print and cursive,
      spelling aloud and in writing, writing numbers and symbols, and visual letter
      recognition and imagery. She was impaired in printing letters, with lowercase
      more affected than uppercase, but her cursive writing was relatively intact. This
      pattern was consistent across letter, word, and nonword writing tasks. She was
      unimpaired on tasks assessing her visual recognition and imagery of lowercase and
      uppercase letters. Her writing of numbers was preserved. J.B.'s handwriting
      disorder was accompanied by a central phonological dysgraphia. Our findings
      indicate functional independence of graphomotor programs for print and cursive
      letter styles and for letters and numbers. We discuss the relationship between
      peripheral and central writing disorders. 

PMID- 24674965
TI  - Altered basal ganglia echogenicity early in sporadic Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by
      conformational alteration of the ubiquitous prion protein. Sporadic CJD appears
      to progress faster if the basal ganglia are shown to be affected on magnetic
      resonance imaging. Transcranial B-mode sonography (TCS) enables visualization of
      differences in tissue echogenicity, which can be associated with changes in the
      cerebral metabolism of various metals. These metabolic changes are considered 1
      of the potential mechanisms of the brain damage in CJD; TCS hyperechogenicity may
      reflect changes in metal homeostasis in CJD. We report a 63-year-old woman who
      presented with typical sporadic CJD. One month after she fell ill, a magnetic
      resonance imaging scan of her brain showed diffuse cortical but no obvious basal
      ganglia involvement. However, TCS revealed moderate hyperechogenicity of both
      lentiform nuclei. The patient's disease progressed quickly and she died 2 months
      later. TCS may show basal ganglia alteration early in the disease course of
      patients with quickly progressing CJD, thus aiding in premortem diagnosis. 

PMID- 24674966
TI  - Neurocognitive impairment in Whipple disease with central nervous system
      involvement.
AB  - Young-onset dementias pose a major challenge to both clinicians and researchers.
      Cognitive decline may be accompanied by systemic features, leading to a diagnosis
      of "dementia plus" syndromes. Whipple disease is a rare systemic illness
      characterized by arthralgias, chronic diarrhea, weight loss, fever, and abdominal
      pain. Central nervous system involvement, including severe cognitive
      deterioration, may precede systemic manifestations, appear during the course of
      the disease, or even be the only symptom. We report a previously highly
      functional 48-year-old man whom we first suspected of having early-onset
      neurodegenerative dementia but then diagnosed with Whipple disease based on a
      detailed clinical and laboratory evaluation. Initial neuropsychological
      evaluation revealed marked impairment in the patient's fluid intelligence and
      severe cognitive deficits in his information processing speed, complex attention,
      memory, visuomotor and construction dexterities, problem solving, and executive
      functions. At neuropsychological follow-up 21 months later, his information
      processing speed had improved only slightly and deficits persisted in his other
      cognitive functions. Repeat brain magnetic resonance imaging at that time showed
      that he had responded to antibiotic treatment. Because Whipple disease can cause
      young-onset "dementia plus" syndromes that may leave patients with neurocognitive
      deficits even after apparently successful treatment, we recommend comprehensive
      neuropsychological assessment for early detection of residual and reversible
      cognitive processes and evaluation of treatment response. 

PMID- 24674968
TI  - Precision attack on calcineurin in macrophages: a new anti-inflammatory weapon.
AB  - Inflammation is a hallmark of many common diseases ranging from arthritis,
      atherosclerosis, or obesity to Alzheimer's disease and cancer. Identifying
      antiinflammatory mechanisms is therefore an important and timely task of modern
      biomedicine. In this issue of The EMBO Journal, a study conducted by Escolano and
      colleagues target a particular interaction site of calcineurin with NFAT in
      macrophages to elicit profound anti-inflammatory effects (Escolano et al, 2014).

PMID- 24674967
TI  - Creb coactivators direct anabolic responses and enhance performance of skeletal
      muscle.
AB  - During the stress response to intense exercise, the sympathetic nervous system
      (SNS) induces rapid catabolism of energy reserves through the release of
      catecholamines and subsequent activation of protein kinase A (PKA).
      Paradoxically, chronic administration of sympathomimetic drugs (beta-agonists)
      leads to anabolic adaptations in skeletal muscle, suggesting that sympathetic
      outflow also regulates myofiber remodeling. Here, we show that beta-agonists or
      catecholamines released during intense exercise induce Creb-mediated
      transcriptional programs through activation of its obligate coactivators Crtc2
      and Crtc3. In contrast to the catabolic activity normally associated with SNS
      function, activation of the Crtc/Creb transcriptional complex by conditional
      overexpression of Crtc2 in the skeletal muscle of transgenic mice fostered an
      anabolic state of energy and protein balance. Crtc2-overexpressing mice have
      increased myofiber cross-sectional area, greater intramuscular triglycerides and
      glycogen content. Moreover, maximal exercise capacity was enhanced after
      induction of Crtc2 expression in transgenic mice. Collectively these findings
      demonstrate that the SNS-adrenergic signaling cascade coordinates a transient
      catabolic stress response during high-intensity exercise, which is followed by
      transcriptional reprogramming that directs anabolic changes for recovery and that
      augments subsequent exercise performance. 

PMID- 24674970
TI  - A method for the efficient cellular uptake and retention of small modified gold
      nanoparticles for the radiosensitization of cells.
AB  - Gold nanoparticles (GNP) enhance the absorbance of photons thereby increasing
      emission of Auger-/photoelectrons in the nm-MUm range. Yet, a major disadvantage
      is their diameter-dependent cellular uptake with an optimum of ~50 nm which may
      not offer optimal radiosensitization. A method was developed to enhance the
      uptake of small GNP. GNP (10nm) were linked to DNA and transferred into HeLa
      cells by transient transfection (GNP-DT). Treatment of cells with GNP-DT resulted
      in a strong perinuclear focal accumulation, whereas this was dimmer and sparser
      for GNP-T (lacking DNA) and close to background levels in GNP-treated cells. Only
      GNP-DT showed a significant radiosensitizing effect (p=0.005) on clonogenic
      survival using clinically relevant megavolt x-rays. Our novel method markedly
      increases the uptake/retention and alters the localization of small GNP in cells
      compared to unmodified GNP. This work finally enables studying the
      radiosensitizing effects of differentially sized GNP. FROM THE CLINICAL EDITOR:
      In an effort to increase the radiosensitization of HeLa cells, his paper
      discusses a transient transfection-based method to enhance gold nanoparticle
      intracellular delivery.

PMID- 24674969
TI  - Immunological memory within the innate immune system.
AB  - Immune memory has traditionally been the domain of the adaptive immune system,
      present only in antigen-specific T and B cells. The purpose of this review is to
      summarize the evidence for immunological memory in lower organisms (which are not
      thought to possess adaptive immunity) and within specific cell subsets of the
      innate immune system. A special focus will be given to recent findings in both
      mouse and humans for specificity and memory in natural killer (NK) cells, which
      have resided under the umbrella of innate immunity for decades. The surprising
      longevity and enhanced responses of previously primed NK cells will be discussed
      in the context of several immunization settings. 

PMID- 24674971
TI  - Nanostructured electrochemical biosensor for th0065 detection of the weak binding
      between the dengue virus and the CLEC5A receptor.
AB  - In this paper, we develop an effective method for detecting weak molecular
      bonding between the dengue virus (DV) and its receptor C-type lectin domain
      family 5, member A (CLEC5A). The CLEC5A-DV interaction is critical for DV-induced
      hemorrhagic fever and shock syndrome, so the sensing of CLEC5A-DV binding is
      crucial to realize a thorough study of the pathogenesis of dengue fever. Through
      a highly sensitive nanostructured sensing electrode of gold nanoparticles (GNPs)
      uniformly deposited on a nanohemisphere array, a label-free detection of the
      ultra weak binding between CLEC5A and the DV can be performed with
      electrochemical impedance spectroscopy (EIS). Experimental results demonstrate
      that the proposed approach is a highly promising method for investigating weak
      molecular interactions such as the ligand-receptor interaction of dengue fever,
      enterovirus (EV), or the interaction between cancer surface glycoproteins and
      their receptors. FROM THE CLINICAL EDITOR: Authors of this study investigated the
      ultra-weak binding between dengue virus and its CLEC5A receptor via
      electrochemical impedance spectroscopy and gold NP sensing electrode. Similar
      methods may be applicable in other infections and in cancer models as well.

PMID- 24674972
TI  - Susceptible genes regulate the adverse effects of TiO2-NPs at predicted
      environmental relevant concentrations on nematode Caenorhabditis elegans.
AB  - Contributions from mutations of susceptible genes to TiO2-NPs toxicity at
      environmental relevant concentrations (ERCs) and the underlying mechanism are
      largely unclear. After prolonged exposure, among the examined 19 mutants
      associated with oxidative stress or stress response, we show that sod-2, sod-3,
      mtl-2, and hsp-16.48 were susceptible genes for TiO2-NPs toxicity on reproduction
      and locomotion behavior, sod-2, sod-3, and mtl-2 were susceptible genes for TiO2
      NPs toxicity on survival and intestinal development, and mtl-2 was susceptible
      gene for TiO2-NPs toxicity on development. Mutations of these susceptible genes,
      together with sensitive endpoints, could be used to evaluate TiO2-NPs toxicity at
      the concentration of 0.0001MUg/L. Our results imply the usefulness of identified
      susceptible genes in assessing the potential nanotoxicity of engineered
      nanomaterial (ENM) at ERCs. One important mechanism to explain property of
      identified susceptible genes for TiO2-NPs toxicity was that mutations of these
      susceptible genes enhanced the uptake of TiO2-NPs into body of nematodes. FROM
      THE CLINICAL EDITOR: This team of authors identified susceptibility genes
      influencing the uptake and consequential toxicity of TiO2 nanoparticles in a
      nematode, highlighting the general importance of investigating genetic influence
      on nanoparticle delivery.

PMID- 24674973
TI  - Abdominal circumference is superior to body mass index in estimating
      musculoskeletal injury risk.
AB  - PURPOSE: The purpose of this study was to compare body mass index (BMI) and
      abdominal circumference (AC) in discriminating individual musculoskeletal injury
      risk within a large population. We also sought to determine whether age or sex
      modulates the interaction between body habitus and injury risk. METHODS: We
      conducted a retrospective cohort study involving 67,904 US Air Force personnel
      from 2005 to 2011. Subjects were stratified by age, sex, BMI, adjusted BMI, and
      AC. New musculoskeletal injuries were recorded relative to body habitus and time
      elapsed from the start of study. RESULTS: Cox proportional hazards regression
      revealed increased HR for musculoskeletal injury in those with high-risk AC
      (males, >39 inches; females, >36 inches) compared with HR in those with low-risk
      AC (males, <=35 inches; females, <=32 inches) in all age categories (18-24 yr: HR
      = 1.567, 95% confidence interval (CI) = 1.327-1.849; 25-34 yr: HR = 2.089, 95% CI
      = 1.968-2.218; >=35 yr: HR = 1.785, 95% CI = 1.651-1.929). HR for obese (BMI,
      >=30 kg.m) compared with that for normal individuals (BMI, <25 kg.m) were less
      elevated. Kaplan-Meier curves showed a dose-response relation in all age groups
      but most prominently in 25- to 34-yr-old participants. Time to injury was
      consistently lowest in 18- to 24-yr-old participants. Score chi-square values,
      indicating comparative strength of each model for injury risk estimation in our
      cohort, were higher for AC than those for BMI or adjusted BMI within all age
      groups. CONCLUSIONS: AC is a better predictor of musculoskeletal injury risk than
      BMI in a large military population. Although absolute injury risk is greatest in
      18- to 24-yr-old participants, the effect of obesity on injury risk is greatest
      in 25- to 34-yr-old participants. There is a dose-response relation between
      obesity and musculoskeletal injury risk, an effect seen with both BMI and AC.

PMID- 24674974
TI  - Muscle inactivity and activity patterns after sedentary time--targeted randomized
      controlled trial.
AB  - PURPOSE: Interventions targeting sedentary time are needed. We used detailed EMG
      recordings to study the short-term effectiveness of simple sedentary time
      targeted tailored counseling on the total physical activity spectrum. METHODS:
      This cluster randomized controlled trial was conducted between 2011 and 2013
      (InPact, ISRCTN28668090), and short-term effectiveness of counseling is reported
      in the present study. A total of 133 office workers volunteered to participate,
      from which muscle activity data were analyzed from 48 (intervention, n = 24;
      control, n = 24). After a lecture, face-to-face tailored counseling was used to
      set contractually binding goals regarding breaking up sitting periods and
      increasing family based physical activity. Primary outcome measures were assessed
      11.8 +/- 1.1 h before and a maximum of 2 wk after counseling including quadriceps
      and hamstring muscle inactivity time, sum of the five longest muscle inactivity
      periods, and light muscle activity time during work, commute, and leisure time.
      RESULTS: Compared with those in the controls, counseling decreased the
      intervention group's muscle inactivity time by 32.6 +/- 71.8 min from 69.1% +/-
      8.5% to 64.6% +/- 10.9% (whole day, P < 0.05; work, P < 0.05; leisure, P < 0.05)
      and the sum of the five longest inactivity periods from 35.6 +/- 14.8 to 29.7 +/-
      10.1 min (whole day, P < 0.05; leisure, P < 0.01). Concomitantly, light muscle
      activity time increased by 20.6 +/- 52.6 min, from 22.2% +/- 7.9% to 25.0% +/-
      9.7% (whole day, P < 0.05; work, P < 0.01; leisure, P < 0.05), and during work
      time, average EMG amplitude (percentage of EMG during maximal voluntary isometric
      contraction (MVC) (%EMG MVC)) increased from 1.6% +/- 0.9% to 1.8% +/- 1.0% (P <
      0.05) in the intervention group compared with that in the controls. CONCLUSIONS:
      A simple tailored counseling was able to reduce muscle inactivity time by 33 min,
      which was reallocated to 21 min of light muscle activity. During work time,
      average EMG amplitude increased by 13%, reaching an average of 1.8% of EMG MVC.
      If maintained, this observed short-term effect may have health-benefiting
      consequences.

PMID- 24674975
TI  - Postexercise cold water immersion benefits are not greater than the placebo
      effect.
AB  - PURPOSE: Despite a general lack of understanding of the underlying mechanisms,
      cold water immersion (CWI) is widely used by athletes for recovery. This study
      examined the physiological merit of CWI for recovery from high-intensity exercise
      by investigating if the placebo effect is responsible for any acute performance
      or psychological benefits. METHODS: Thirty males (mean +/- SD: age, 24 +/- 5 yr;
      VO2 peak, 51.1 +/- 7.0 mL . kg(-1) . min(-1)) performed an acute high-intensity
      interval training session, comprised of 4 * 30-s sprints, immediately followed by
      one of the following three 15-min recovery conditions: CWI (10.3 degrees C +/-
      0.2 degrees C), thermoneutral water immersion placebo (TWP) (34.7 degrees C +/-
      0.1 degrees C), or thermoneutral water immersion control (TWI) (34.7 degrees C +/
      0.1 degrees C). An intramuscular thermistor was inserted during exercise and
      recovery to record muscle temperature. Swelling (thigh girth), pain
      threshold/tolerance, interleukin 6 concentration, and total leukocyte,
      neutrophil, and lymphocyte counts were recorded at baseline, postexercise,
      postrecovery, and 1, 24, and 48 h postexercise. A maximal voluntary isometric
      contraction (MVC) of the quadriceps was performed at the same time points, with
      the exception of postexercise. Self-assessments of readiness for exercise,
      fatigue, vigor, sleepiness, pain, and belief of recovery effectiveness were also
      completed. RESULTS: Leg strength after the MVC and ratings of readiness for
      exercise, pain, and vigor were significantly impaired in TWI compared with those
      in CWI and TWP which were similar to each other. CONCLUSIONS: A recovery placebo
      administered after an acute high-intensity interval training session is superior
      in the recovery of muscle strength over 48 h as compared with TWI and is as
      effective as CWI. This can be attributed to improved ratings of readiness for
      exercise, pain, and vigor, suggesting that the commonly hypothesized
      physiological benefits surrounding CWI are at least partly placebo related.

PMID- 24674976
TI  - Hypoxic training: effect on mitochondrial function and aerobic performance in
      hypoxia.
AB  - PURPOSE: The effects of hypoxic training on exercise performance remain
      controversial. Here, we tested the hypotheses that i) hypoxic training possesses
      ergogenic effects at sea level and altitude and ii) the benefits are primarily
      mediated by improved mitochondrial function of the skeletal muscle. METHODS: We
      determined aerobic performance (incremental test to exhaustion and time trial for
      a set amount of work) in moderately trained subjects undergoing 6 wk of endurance
      training (3-4 times per week, 60 min per session) in normoxia (placebo, n = 8) or
      normobaric hypoxia (FIO2 = 0.15, n = 9) using a double-blind and randomized
      design. Exercise tests were performed in normoxia and acute hypoxia (FIO2 =
      0.15). Skeletal muscle mitochondrial respiratory capacities and electron coupling
      efficiencies were measured via high-resolution respirometry. Total hemoglobin
      mass was assessed by carbon monoxide rebreathing. RESULTS: Skeletal muscle
      respiratory capacity was not altered by training or hypoxia; however, electron
      coupling control respective to fat oxidation slightly diminished with hypoxic
      training. Hypoxic training did increase total hemoglobin mass more than the
      placebo (8.4% vs 3.3%, P = 0.02). In normoxia, hypoxic training had no additive
      effect on maximal measures of oxygen uptake or time trial performance. In acute
      hypoxia, hypoxic training conferred no advantage on maximal oxygen uptake but
      tended to enhance time trial performance more than normoxic training (52% vs 32%,
      P = 0.09). CONCLUSIONS: Our data suggest that, in moderately trained subjects, 6
      wk of hypoxic training possesses no ergogenic effect at sea level. It is not
      excluded that hypoxic training might facilitate endurance capacity at moderate
      altitude; however, this issue is still open and needs to be further examined.

PMID- 24674977
TI  - Effects of substituting sedentary time with physical activity on metabolic risk.
AB  - PURPOSE: The detrimental effects of sedentary time on health may act by replacing
      time spent in physical activities. The aim of this study was to examine cross
      sectional associations between objectively assessed sedentary and physical
      activity domains and cardiometabolic risk factors using a novel isotemporal
      substitution paradigm. METHODS: Participants were 445 healthy men and women (mean
      age, 66 +/- 6 yr), without history or objective signs of cardiovascular disease,
      drawn from the Whitehall II epidemiological cohort. Physical activity was
      objectively measured using accelerometers (ActiGraph GT3X) worn around the waist
      during waking hours for 4-7 consecutive days. We examined the effects of
      replacing sedentary time with light activity or moderate-to-vigorous physical
      activity (MVPA) on a range of risk factors (HDL cholesterol, triglycerides,
      HbA1c, and body mass index) using an isotemporal substitution paradigm. RESULTS:
      In partition models, where the time in each of the intensity categories was held
      constant, only MVPA remained associated with risk factors. In isotemporal
      substitution models that held total (wear) time constant, replacing 10-min
      sedentary time with an equal amount of MVPA was associated with favorable effects
      in all risk factors, including HbA1c (B = -0.023; 95% confidence interval (CI), 
      0.043 to -0.002), BMI (B = -0.39; 95% CI, -0.54 to -0.24), HDL cholesterol (B =
      0.037; 95% CI, 0.021-0.054), and triglycerides (B = -0.035; 95% CI, -0.061 to 
      0.009). CONCLUSIONS: The associations between sedentary behavior and
      cardiometabolic risk may be dependent on the types of activities that are
      displaced by sedentary time.

PMID- 24674978
TI  - Differential modulation of clock gene expression in the suprachiasmatic nucleus,
      liver and heart of aged mice.
AB  - Studies on the molecular clockwork during aging have been hitherto addressed to
      core clock genes. These previous investigations indicate that circadian profiles
      of core clock gene expression at an advanced age are relatively preserved in the
      master circadian pacemaker and the hypothalamic suprachiasmatic nucleus (SCN),
      and relatively impaired in peripheral tissues. It remains to be clarified whether
      the effects of aging are confined to the primary loop of core clock genes, or
      also involve secondary clock loop components, including Rev-erbalpha and the
      clock-controlled genes Dbp and Dec1. Using quantitative real-time RT-PCR, we here
      report a comparative analysis of the circadian expression of canonical core clock
      genes (Per1, Per2, Cry1, Cry2, Clock and Bmal1) and non-core clock genes (Rev
      erbalpha, Dbp and Dec1) in the SCN, liver, and heart of 3month-old vs 22month-old
      mice. The results indicate that circadian clock gene expression is significantly
      modified in the SCN and peripheral oscillators of aged mice. These changes are
      not only highly tissue-specific, but also involve different clock gene loops. In
      particular, we here report changes of secondary clock loop components in the SCN,
      changes of the primary clock loop in the liver, and minor changes of clock gene
      expression in the heart of aged mice. The present findings outline a track to
      further understanding of the role of primary and secondary clock loop components
      and their crosstalk in the impairment of circadian output which characterizes
      aging. 

PMID- 24674979
TI  - Acute drop in blood monocyte count differentiates NEC from other causes of
      feeding intolerance.
AB  - OBJECTIVE: Necrotizing enterocolitis (NEC) is characterized by macrophage
      infiltration into affected tissues. Because intestinal macrophages are derived
      from recruitment and in situ differentiation of blood monocytes in the gut
      mucosa, we hypothesized that increased recruitment of monocytes to the intestine
      during NEC reduces the blood monocyte concentration and that this fall in blood
      monocytes can be a useful biomarker for NEC. STUDY DESIGN: We reviewed medical
      records of very-low-birth-weight (VLBW) infants treated for NEC and compared them
      with a matched control group comprised of infants with feeding intolerance but no
      signs of NEC. Clinical characteristics and absolute monocyte counts (AMCs) were
      recorded. Diagnostic accuracy of AMC values was tested using receiver-operator
      characteristics (ROC). RESULT: We compared 69 cases and 257 controls (median 27
      weeks, range 26 to 29 in both the groups). In stage II NEC, AMCs decreased from
      median 1.7 * 10(9) l(-1) (interquartile range (IQR) 0.98 to 2.4) to 0.8 (IQR 0.62
      to 2.1); P < 0.05. In stage III NEC, monocyte counts decreased from median 2.1 *
      10(9) l(-1) (IQR 0.1.5 to 3.2) to 0.8 (IQR 0.6 to 1.9); P < 0.05. There was no
      change in AMCs in control infants. ROC of AMC values showed a diagnostic accuracy
      (area under the curve) of 0.76. In a given infant with feeding intolerance, a
      drop in AMCs of > 20% indicated NEC with sensitivity of 0.70 (95% confidence
      interval (CI) 0.57 to 0.81) and specificity of 0.71 (95% CI 0.64 to 0.77).
      CONCLUSION: We have identified a fall in blood monocyte concentration as a novel
      biomarker for NEC in VLBW infants.

PMID- 24674980
TI  - Obstructive sleep apnea in pregnancy: reliability of prevalence and prediction
      estimates.
AB  - OBJECTIVE: We sought to ascertain the validity of two screening scales for
      obstructive sleep apnea (OSA) in pregnancy and to establish the prevalence of OSA
      in pregnancy. STUDY DESIGN: In this prospective observational study, two
      screening scales were administered. Screen positive subjects were referred for
      diagnostic polysomnography (PSG); if admitted for antepartum care, screen
      positive subjects underwent a modified study with a type 3 device (T3D). RESULT:
      A total of 1509 subjects underwent OSA screening; 58 completed diagnostic
      testing. Neither measure was a reliable diagnostic tool for OSA as determined by
      T3D or PSG (detection rates of 10.3% and 18.0%, respectively). Among screen
      positive subjects undergoing PSG or T3D testing, 15.5% ultimately met 'gold
      standard' OSA diagnostic criteria for an estimated point prevalence of 4.9%.
      CONCLUSION: In this prospective trial, screening positive on the Berlin
      questionnaire or Epworth sleepiness scale was poorly predictive of OSA among
      gravidae and was associated with a high false referral rate.

PMID- 24674981
TI  - Impact of lactation stage, gestational age and mode of delivery on breast milk
      microbiota.
AB  - OBJECTIVE: There is an increasing evidence of the immunological role of breast
      milk (BM) microbiota on infant health. This study aims to analyze several
      determining factors of milk microbiota. STUDY DESIGN: A total of 96 milk samples
      from 32 healthy mothers (19 preterm vs 13 at term gestations; and 15 vaginal
      deliveries vs 17 Cesarean sections) were longitudinally collected. Microbiota
      composition was studied by quantitative PCR and the influence of lactation stage,
      gestational age and delivery mode was evaluated. RESULT: Globally, Lactobacillus,
      Streptococcus and Enterococcus spp. were the predominant bacterial groups. Total
      bacteria, Bifidobacterium and Enterococcus spp. counts increased throughout the
      lactation period. At all lactation stages, Bifidobacterium spp. concentration was
      significantly higher in milk samples from at term gestations than in preterm
      gestations. Higher bacterial concentrations in colostrum and transitional milk
      were found in Cesarean sections. Nevertheless, Bifidobacterium was detected more
      frequently in vaginal than in Cesarean deliveries. CONCLUSION: Lactation stage,
      gestational age and delivery mode all influence the composition of several
      bacteria inhabiting BM: Bifidobacterium, Lactobacillus, Staphylococcus,
      Streptococcus and Enterococcus spp., and, consequently, may affect the infant's
      early intestinal colonization.

PMID- 24674982
TI  - Lipid peroxidation, DNA damage and total antioxidant status in neonatal
      hyperbilirubinemia.
AB  - OBJECTIVE: Lipid peroxidation, DNA damage and total antioxidant status (TAS) were
      assessed in neonates with unconjugated hyperbilirubinemia (UCH). STUDY DESIGN:
      Plasma malondialdehyde (MDA), 8-hydroxy-2-deoxy-guanosine (8-OH-dG) and TAS
      levels were compared between 64 term newborns with idiopathic UCH and 30 age
      matched healthy controls. RESULT: Compared with controls, an overall increase in
      mean plasma MDA and 8-OH-dG levels and a decrease in TAS level were noted in the
      UCH group. Within the UCH group, mean plasma MDA level was found to be low in
      infants with lower bilirubin levels, but a progressive increase was documented
      above the bilirubin level of 20 mg dl(-1). A significant increase in 8-OH-dG
      level was documented even at lower bilirubin levels, and a decrease i plasma TAS
      level was found at bilirubin levels above 16 mg dl(-1). MDA and 8-OH-dG levels
      were significantly higher, whereas TAS level was significantly lower in five
      neonates who developed features of acute bilirubin encephalopathy compared with
      those with normal outcome. Alteration of MDA, 8-OH-dG and TAS levels showed high
      predictive accuracy for poor outcome. CONCLUSION: Moderate-to-severe UCH was
      associated with higher oxidative stress and lower antioxidant defense. Alteration
      of oxidative stress parameters may be utilized as early predictors for poor
      outcome. High DNA damage even at lower bilirubin levels suggests possible
      genotoxic effect of bilirubin in UCH.

PMID- 24674983
TI  - A prospective study on hyperglycemia and retinopathy of prematurity.
AB  - OBJECTIVE: Retinopathy of prematurity (ROP) constitutes a significant morbidity
      in premature infants that can lead to blindness. Multiple retrospective studies
      have identified neonatal hyperglycemia as a risk for developing ROP. However, in
      the absence of any reported prospective study, it is not clear whether
      hyperglycemia is associated with ROP independent of the commonly associated
      comorbidities. The objective of this study was to investigate whether
      hyperglycemia in premature infants is independently associated with ROP. STUDY
      DESIGN: Premature infants (<1500 g or?32 weeks gestational age) were enrolled in
      a prospective longitudinal cohort study. All demographic, clinical and laboratory
      data were collected. Bedside whole-blood glucose concentration was measured every
      8 h daily for 7 days. For any glucose reading<50 or>150 mg dl(-1), serum sample
      was sent to the laboratory for confirmation. Hyperglycemia was defined as any
      blood glucose level?150 mg dl(-1). ROP patients were compared with non-ROP
      patients in a bivariate analysis. Variables significantly associated with ROP
      were studied in a logistic regression model. RESULT: A total of 65 patients were
      enrolled with gestational age 31.1+/-1.2 weeks and birth weight 1385+/-226 g.
      Thirty-one patients (48%) were identified with hyperglycemia. On eye examination,
      19 cases (29.2%) had ROP (13 with stage 1, 4 with stage 2 and 2 with stage 3).
      There were more cases of ROP in the hyperglycemia group compared with the
      euglycemia group (45% vs 15%, P=0.007). Patients who developed ROP had
      significantly higher maximum and average glucose concentrations when compared
      with non-ROP patients. Multiple factors have been associated with ROP on
      bivariate analysis, including gestational age, exposure to oxygen, respiratory
      support and poor weight gain. However, in a logistic regression model including
      all significant variables, average blood glucose in the first week of life was
      the factor independently associated with ROP with an odds ratio of: 1.77 (95%
      confidence interval: 1.08 to 2.86), P=0.024. CONCLUSION: In a cohort of premature
      infants, elevated average blood glucose concentrations in the first week of life
      is independently associated with the development of ROP.

PMID- 24674985
TI  - The elements of dermatology: the legacy of Covisa and Bejarano.
AB  - In 1936, Covisa and Bejarano published a treatise entitled Elementos de
      Dermatologia (The Elements of Dermatology). In this surprisingly modern book they
      abandoned the nosological debates characteristic of the 19th century and instead
      classified diseases according to their etiology and pathogenesis based on the
      scientific and technical advances of the time. Moreover, unlike other books
      available at the time, which were essentially adaptations of foreign texts, this
      was the first medical work to reflect the reality of Spanish medicine. However,
      the future of both the book and its authors was to be determined by the start of
      the Spanish Civil War in the same year. Covisa and Bejarano, who were both
      extremely active in the public health system and medical education during the
      Second Republic, were obliged to seek exile in America. Due to the difficulties
      of the time, very few copies of the book reached the public and no new editions
      were ever printed. We will never know what would have happened if the war had not
      started, but we believe that this important work should be remembered. 

PMID- 24674984
TI  - Zooming in on disordered systems: neutron reflection studies of proteins
      associated with fluid membranes.
AB  - Neutron reflectometry (NR) is an emerging experimental technique for the
      structural characterization of proteins interacting with fluid bilayer membranes
      under conditions that mimic closely the cellular environment. Thus, cellular
      processes can be emulated in artificial systems and their molecular basis studied
      by adding cellular components one at a time in a well-controlled environment
      while the resulting structures, or structural changes in response to external
      cues, are monitored with neutron reflection. In recent years, sample
      environments, data collection strategies and data analysis were continuously
      refined. The combination of these improvements increases the information which
      can be obtained from NR to an extent that enables structural characterization of
      protein-membrane complexes at a length scale that exceeds the resolution of the
      measurement by far. Ultimately, the combination of NR with molecular dynamics
      (MD) simulations can be used to cross-validate the results of the two techniques
      and provide atomic-scale structural models. This review discusses these
      developments in detail and demonstrates how they provide new windows into
      relevant biomedical problems. This article is part of a Special Issue entitled:
      Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and
      Kalina Hristova. 

PMID- 24674986
TI  - Measuring and modelling seasonal patterns of carbohydrate storage and
      mobilization in the trunks and root crowns of peach trees.
AB  - BACKGROUND AND AIMS: Developing a conceptual and functional framework for
      simulating annual long-term carbohydrate storage and mobilization in trees has
      been a weak point for virtually all tree models. This paper provides a novel
      approach for solving this problem using empirical field data and details of
      structural components of simulated trees to estimate the total carbohydrate
      stored over a dormant season and available for mobilization during spring
      budbreak. METHODS: The seasonal patterns of mobilization and storage of non
      structural carbohydrates in bark and wood of the scion and rootstock crowns of
      the trunks of peach (Prunus persica) trees were analysed subsequent to treatments
      designed to maximize differences in source-sink behaviour during the growing
      season. Mature peach trees received one of three treatments (defruited and no
      pruning, severe pruning to 1.0 m, and unthinned with no pruning) in late winter,
      just prior to budbreak. Selected trees of each treatment were harvested at four
      times (March, June, August and November) and slices of trunk and root crown
      tissue above and below the graft union were removed for carbohydrate analysis.
      Inner bark and xylem tissues from the first to fifth rings were separated and
      analysed for non-structural carbohydrates. Data from these experiments were then
      used to estimate the amount of non-structural carbohydrates available for
      mobilization and to parameterize a carbohydrate storage sub-model in the
      functional-structural L-PEACH model. KEY RESULTS: The mass fraction of
      carbohydrates in all sample tissues decreased from March to June, but the
      decrease was greatest in the severely pruned and unthinned treatments. November
      carbohydrate mass fractions in all tissues recovered to values similar to those
      in the previous March, except in the older xylem rings of the severely pruned and
      unthinned treatment. Carbohydrate storage sink capacity in trunks was empirically
      estimated from the mean maximum measured trunk non-structural carbohydrate mass
      fractions. The carbohydrate storage source available for mobilization was
      estimated from these maximum mass fractions and the early summer minimum mass
      fractions remaining in these tissues in the severe treatments that maximized
      mobilization of stored carbohydrates. The L-PEACH sink-source carbohydrate
      distribution framework was then used along with simulated tree structure to
      successfully simulate annual carbohydrate storage sink and source behaviour over
      years. CONCLUSIONS: The sink-source concept of carbohydrate distribution within a
      tree was extended to include winter carbohydrate storage and spring mobilization
      by considering the storage sink and source as a function of the collective
      capacity of active xylem and phloem tissue of the tree, and its annual behaviour
      was effectively simulated using the L-PEACH functional-structural plant model.

PMID- 24674987
TI  - Local coordination of Fe3+ in ZnO nanoparticles: multi-frequency electron
      paramagnetic resonance (EPR) and Newman superposition model analysis.
AB  - Iron-doped ZnO nanoparticles have been synthesized through high-energy ball
      milling of powders produced by the co-precipitation method. Fine particles with
      an average size down to 40 nm have been obtained after 15 min of milling. Fe(3+)
      cations have been incorporated into the ZnO lattice within the limits of the
      solubility. By using multi-frequency and high-field electron paramagnetic
      resonance (EPR) we have resolved all electronic transitions for the S = 5/2 high
      spin system and have accurately determined the EPR spin-Hamiltonian parameters.
      By combining data from crystallographic x-ray diffraction and EPR with the semi
      empirical Newman superposition model we have found the local configurational
      position of Fe(3+) and have confirmed the symmetry of the lattice. Results
      presented in this paper indicate that Fe cations most probably substitute at Zn
      sites in ZnO. At nanosizes the effect of Fe(3+) cations on the surface becomes
      remarkable: additional size effects can be observed in the EPR spectrum, which
      are different from the spectrum of bulk. 

PMID- 24674988
TI  - Measurement of concentrations of whole blood levels of choline, betaine, and
      dimethylglycine and their relations to plasma levels.
AB  - We aimed at developing a method for the measurement of choline and its
      metabolites in whole blood (WB). After an extraction step, quantification of
      choline, betaine, and dimethylglycine (DMG) was performed using ultra performance
      liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Plasma and WB
      metabolites were evaluated in a group of 61 elderly people. The calibration
      curves were linear (r(2)>0.997) for all compounds. The inter- and intra-assay
      coefficients of variation for all analytes were <10%. The recoveries were >90%
      and the relative matrix effect were <=4.0%. The median concentrations of choline,
      betaine, and DMG were 11.3, 27.8, and 5.9MUmol/L in plasma and 66.6, 165, and
      13.7MUmol/L in WB, respectively. There were positive correlations between WB and
      plasma markers; for choline (r=0.42), betaine (r=0.61), and DMG (r=0.56) (all
      p<=0.001). The concentrations of betaine in WB and plasma were significantly
      higher in men than in women. The concentrations of WB choline and DMG did not
      differ significantly according to sex. In conclusion, we have established a
      reliable method for measuring choline metabolites in WB. The concentrations of WB
      choline, betaine, and DMG seem to reflect intracellular concentrations of these
      metabolites. 

PMID- 24674989
TI  - High performance liquid chromatographic method for the determination of
      cinepazide maleate and its application to a pharmacokinetic study in rats.
AB  - A simple and reliable high performance liquid chromatographic (HPLC) method has
      been developed and validated to quantify cinepazide maleate, a calcium blocker,
      in rat plasma. Cinepazide maleate and Tinidazole (internal standard) have been
      extracted by a simple liquid-liquid extraction before injection into
      chromatographic system. Chromatographic separation was achieved on a reversed
      phase C18 column with a mobile phase consisted of a water mixture of 10mM
      potassium dihydrogen phosphate (pH=4.5):methanol (40:60, v/v), pumped at flow
      rate of 1.0mL/min, and detected at 303nm. The method exhibited a linear range of
      0.12-120MUg/mL in blank rat plasma, with the lower detection limit of 0.06MUg/mL.
      The method was statistically validated for linearity, accuracy, precision,
      selectivity and stability following FDA guidelines. The intra- and inter-assay
      coefficients of variation did not exceed +/-15% from the nominal concentration.
      The accuracy of cinepazide maleate was within +/-15% of the theoretical value.
      The assay has been applied successfully in a pharmacokinetic study of cinepazide
      maleate after a single intravenous at three doses in rat. And cinepazide maleate
      injection can improve the bioavailability of cinepazide maleate greatly, and has
      a dose-dependence profile in rats. 

PMID- 24674990
TI  - Methodological considerations for the harmonization of non-cholesterol sterol bio
      analysis.
AB  - Non-cholesterol sterols (NCS) are used as surrogate markers of cholesterol
      metabolism which can be measured from a single blood sample. Cholesterol
      precursors are used as markers of endogenous cholesterol synthesis and plant
      sterols are used as markers of cholesterol absorption. However, most aspects of
      NCS analysis show wide variability among researchers within the area of
      biomedical research. This variability in methodology is a significant contributor
      to variation between reported NCS values and hampers the confidence in comparing
      NCS values across different research groups, as well as the ability to conduct
      meta-analyses. This paper summarizes the considerations and conclusions of a
      workshop where academic and industrial experts met to discuss NCS measurement.
      Highlighted is why each step in the analysis of NCS merits critical
      consideration, with the hopes of moving toward more standardized and comparable
      NCS analysis methodologies. Alkaline hydrolysis and liquid-liquid extraction of
      NCS followed by parallel detection on GC-FID and GC-MS is proposed as an ideal
      methodology for the bio-analysis of NCS. Furthermore the importance of cross
      comparison or round robin testing between various groups who measure NCS is
      critical to the standardization of NCS measurement. 

PMID- 24674991
TI  - Generation of human endometrial knockout cell lines with the CRISPR/Cas9 system
      confirms the prostaglandin F2alpha synthase activity of aldo-ketoreductase 1B1.
AB  - Prostaglandins (PGs) are important regulators of female reproductive function.
      The primary PGs produced in the endometrium are PGE2 and PGF2alpha. Relatively
      little is known about the biosynthetic pathways leading to the formation of
      PGF2alpha. We have described the role of aldo-ketoreductase (AKR)1B1 in increased
      PGF2alpha production by human endometrial cells following stimulation with
      interleukin-1beta (IL-1beta). However, alternate PGF synthases are expressed
      concurrently in endometrial cells. A definite proof of the role of AKR1B1 would
      require gene knockout; unfortunately, this gene has no direct equivalent in the
      mouse. Recently, an efficient genome-editing technology using RNA-guided DNase
      Cas9 and the clustered regularly interspaced short palindromic repeats (CRISPR)
      system has been developed. We have adapted this approach to knockout AKR1B1 gene
      expression in human endometrial cell lines. One clone (16-2) of stromal origin
      generated by the CRISPR/Cas9 system exhibited a complete loss of AKR1B1 protein
      and mRNA expression, whereas other clones presented with partial edition. The
      present report focuses on the characterization of clone 16-2 exhibiting deletion
      of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this
      clone lost their ability to produce PGF2alpha but maintained their original
      stromal cell (human endometrial stromal cells-2) phenotype including the capacity
      to decidualize in the presence of progesterone (medroxyprogesterone acetate) and
      8-bromo-cAMP. Knockout cells also maintained their ability to increase PGE2
      production in response to IL-1beta. In summary, we demonstrate that the new
      genome editing CRISPR/Cas9 system can be used in human cells to generate stable
      knockout cell line models. Our results suggest that genome editing of human cell
      lines can be used to complement mouse KO models to validate the function of genes
      in differentiated tissues and cells. Our results also confirm that AKR1B1 is
      involved in the synthesis of PGF2alpha. 

PMID- 24674992
TI  - Potential role of endometrial stem/progenitor cells in the pathogenesis of early
      onset endometriosis.
AB  - The pathogenesis of early-onset endometriosis has recently been revisited,
      sparked by the discovery of endometrial stem/progenitor cells and their possible
      role in endometriosis, and because maternal pregnancy hormone withdrawal
      following delivery induces uterine bleeding in the neonate. The neonatal uterus
      has a large cervix to corpus ratio which is functionally blocked with mucous,
      supporting the concept of retrograde shedding of neonatal endometrium. Only 5%
      show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal
      girls and even in severe stage in adolescents supports the theory that early
      onset endometriosis may originate from retrograde uterine bleeding soon after
      birth. Endometrial stem/progenitor cells have been identified in menstrual blood
      suggesting that they may also be shed during neonatal uterine bleeding. Thus, we
      hypothesized that stem/progenitor cells present in shedding endometrium may have
      a role in the pathogenesis of early-onset endometriosis through retrograde
      neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed
      endometrial stem/progenitor cells are postulated to survive in the pelvic cavity
      in the absence of circulating estrogens supported by niche cells also shed during
      neonatal uterine bleeding. According to this hypothesis, during thelarche, under
      the influence of rising estrogen levels, endometrial stem/progenitor cells
      proliferate and establish ectopic endometrial lesions characteristic of
      endometriosis. This New Research Horizon review builds on recent discussions on
      the pathogenesis of early-onset endometriosis and raises new avenues for research
      into this costly condition. 

PMID- 24674993
TI  - Metabolic gene profile in early human fetal heart development.
AB  - The primitive cardiac tube starts beating 6-8 weeks post fertilization in the
      developing embryo. In order to describe normal cardiac development during late
      first and early second trimester in human fetuses this study used microarray and
      pathways analysis and created a corresponding 'normal' database. Fourteen fetal
      hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were
      prospectively collected at the time of elective termination of pregnancy. RNA
      from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST
      microarray chip. From the amassed data we investigated differences in cardiac
      development within the 10-18 GA period dividing the sample by GA in three groups:
      10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted
      for a false discovery rate of 5% was used as initial cutoff to determine
      differential gene expression for individual genes. Test for enrichment to
      identify functional groups was carried out using the Gene Ontology (GO) and the
      Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly
      identified the cardiac specific genes, and transcripts reported to be
      differentially expressed were confirmed by qRT-PCR. Single transcript and
      Ontology analysis showed first trimester heart expression of myosin-related genes
      to be up-regulated >5-fold compared with second trimester heart. In contrast the
      second trimester hearts showed further gestation-related increases in many genes
      involved in energy production and cardiac remodeling. In conclusion, fetal heart
      development during the first trimester was dominated by heart-specific genes
      coding for myocardial development and differentiation. During the second
      trimester, transcripts related to energy generation and cardiomyocyte
      communication for contractile coordination/proliferation were more dominant.
      Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and
      clearly increase as the heart matures. Retinol receptor and gamma-aminobutyric
      acid (GABA) receptor transcripts were detected, and have not been described
      previously in human fetal heart during this period. For the first time global
      gene expression of heart has been described in human samples to create a database
      of normal development to understand and compare with known abnormal fetal heart
      development. 

PMID- 24674994
TI  - Correction.

PMID- 24674995
TI  - An observational study of giant cell interstitial pneumonia and lung fibrosis in
      hard metal lung disease.
AB  - BACKGROUND: Hard metal lung disease has various pathological patterns including
      giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP).
      Although the UIP pattern is considered the prominent feature in advanced disease,
      it is unknown whether GIP finally progresses to the UIP pattern. OBJECTIVES: To
      clarify clinical, pathological and elemental differences between the GIP and UIP
      patterns in hard metal lung disease. METHODS: A cross-sectional study of patients
      from 17 institutes participating in the 10th annual meeting of the Tokyo Research
      Group for Diffuse Parenchymal Lung Diseases, 2009. Nineteen patients (seven
      female) diagnosed with hard metal lung disease by the presence of tungsten in
      lung specimens were studied. RESULTS: Fourteen cases were pathologically
      diagnosed as GIP or centrilobular inflammation/fibrosing. The other five cases
      were the UIP pattern or upper lobe fibrosis. Elemental analyses of lung specimens
      of GIP showed tungsten throughout the centrilobular fibrotic areas. In the UIP
      pattern, tungsten was detected in the periarteriolar area with subpleural
      fibrosis, but no association with centrilobular fibrosis or inflammatory cell
      infiltration. The GIP group was younger (43.1 vs 58.6 years), with shorter
      exposure duration (73 vs 285 months; p<0.01), lower serum KL-6 (398 vs 710 U/mL)
      and higher lymphocyte percentage in bronchoalveolar lavage fluid (31.5% vs 3.22%;
      p<0.05) than the fibrosis group. CONCLUSIONS: The UIP pattern or upper lobe
      fibrosis is remarkably different from GIP in distribution of hard metal elements,
      associated interstitial inflammation and fibrosis, and clinical features. In hard
      metal lung disease, the UIP pattern or upper lobe fibrosis may not be an advanced
      form of GIP.

PMID- 24674996
TI  - Growth trajectories in the children of mothers with eating disorders: a
      longitudinal study.
AB  - OBJECTIVE: The aim of this study was to examine longitudinal patterns of growth
      trajectories in children of women with eating disorders (ED): anorexia nervosa
      (AN) and bulimia nervosa (BN). DESIGN: Prospective longitudinal birth cohort;
      Avon Longitudinal Study of Parents and Children (ALSPAC). SETTING: South West
      England, UK. PARTICIPANTS: The sample consisted of women and their children (n=10
      190) from ALSPAC. Patterns of growth among children of women reporting a history
      of AN (n=137), BN (n=165), both AN and BN (n=68) and other psychiatric disorders
      (n=920) were compared with an unexposed group of children (n=8900). MAIN OUTCOME
      MEASURES: Height and weight data, from birth to 10 years, were extracted from
      health visitor records, parental report from questionnaires and clinic
      attendances. Growth trajectories were analysed using mixed-effects models and
      constructed separately for male and female children. RESULTS: Between birth and
      10 years, male children of women with BN were taller than children in the
      unexposed group. Male children of women with a history of AN and BN, and female
      children of women with AN, were shorter throughout childhood. Between the ages of
      2 and 5, higher body mass index (BMI) was observed in male children in all
      maternal ED groups. Conversely, female children of women with AN had a BMI of 
      0.35 kg/m(2) lower at 2 years compared with the unexposed group, with catch-up by
      age 10. CONCLUSIONS: Early childhood growth has been found to predict weight gain
      in adolescence and adulthood, and may be a risk factor for the development of an
      ED. These findings therefore have public health implications in relation to the
      prevention of weight-related and eating-related disorders later in life.

PMID- 24674997
TI  - A new tool for converting food frequency questionnaire data into nutrient and
      food group values: FETA research methods and availability.
AB  - OBJECTIVES: To describe the research methods for the development of a new open
      source, cross-platform tool which processes data from the European Prospective
      Investigation into Cancer and Nutrition Norfolk Food Frequency Questionnaire
      (EPIC-Norfolk FFQ). A further aim was to compare nutrient and food group values
      derived from the current tool (FETA, FFQ EPIC Tool for Analysis) with the
      previously validated but less accessible tool, CAFE (Compositional Analyses from
      Frequency Estimates). The effect of text matching on intake data was also
      investigated. DESIGN: Cross-sectional analysis of a prospective cohort study-EPIC
      Norfolk. SETTING: East England population (city of Norwich and its surrounding
      small towns and rural areas). PARTICIPANTS: Complete FFQ data from 11 250 men and
      13 602 women (mean age 59 years; range 40-79 years). OUTCOME MEASURES: Nutrient
      and food group intakes derived from FETA and CAFE analyses of EPIC-Norfolk FFQ
      data. RESULTS: Nutrient outputs from FETA and CAFE were similar; mean (SD) energy
      intake from FETA was 9222 kJ (2633) in men, 8113 kJ (2296) in women, compared
      with CAFE intakes of 9175 kJ (2630) in men, 8091 kJ (2298) in women. The majority
      of differences resulted in one or less quintile change (98.7%). Only mean daily
      fruit and vegetable food group intakes were higher in women than in men (278 vs
      212 and 284 vs 255 g, respectively). Quintile changes were evident for all
      nutrients, with the exception of alcohol, when text matching was not executed;
      however, only the cereals food group was affected. CONCLUSIONS: FETA produces
      similar nutrient and food group values to the previously validated CAFE but has
      the advantages of being open source, cross-platform and complete with a data
      entry form directly compatible with the software. The tool will facilitate
      research using the EPIC-Norfolk FFQ, and can be customised for different study
      populations.

PMID- 24674998
TI  - Conserved alanine rich protein Rv3878 in Mycobacterium tuberculosis contains
      sequence polymorphisms.
AB  - Host immune pressure and associated parasite immune evasion are key features of
      host-pathogen co-evolution. A previous study showed that human T cell epitopes of
      Mycobacterium tuberculosis are evolutionarily hyperconserved and thus it was
      deduced that M. tuberculosis lacks antigenic variation and immune evasion. Here,
      we selected 162 clinical M. tuberculosis complex (MTBC) isolates from China,
      amplified gene encoding Rv3878 and compared the sequences. The results showed
      that Rv3878, a conserved hypothetical alanine rich protein, is not conserved in
      M. tuberculosis strains and there are polymorphisms existing in the protein. The
      large number of amino acid changes in its T cell epitopes may reflect ongoing
      immune evasion. 

PMID- 24674999
TI  - Nasal nitric oxide is associated with exhaled NO, bronchial responsiveness and
      poor asthma control.
AB  - The fraction of exhaled nitric oxide (FeNO) is an established marker of airway
      inflammation in asthma. Nasal nitric oxide (nNO) has initially been regarded as a
      promising marker of inflammation of nasal mucosa. However, due to its dual
      origins, paranasal sinuses and nasal mucosa, the clinical use of nNO is
      controversial. There is an inflammatory link between inflammation in the upper
      and lower airways within the united airways' paradigm, but the study of the
      clinical value of nNO in asthma has been limited. The objective of this study is
      to analyse nNO in asthmatics and its relationship to FeNO, bronchial
      hyperresponsiveness, allergic sensitization and asthma control. A total of 371
      children and young adults from an asthma cohort were included in this study,
      which performed measurements of nNO (through aspiration at 5 mL s(-1)), FeNO,
      bronchial responsiveness to methacholine, blood eosinophil count (B-Eos) and IgE
      sensitization. The asthma control test (ACT) and a questionnaire regarding
      medical treatment, symptoms of asthma, rhinitis and chronic rhinosinusitis were
      completed by all subjects. An association was found between higher nNO levels and
      increased bronchial responsiveness (p < 0.001), FeNO (p < 0.001) and B-Eos (p =
      0.002). Sensitization to furry animals related to higher levels of nNO (p <
      0.001). Subjects with poorly controlled asthma (ACT < 15) had lower levels of nNO
      than subjects with a higher ACT score (619 +/- 278 ppb, versus 807 +/- 274 ppb, p
      = 0.002). Loss of smell showed the strongest association with lower nNO levels
      among the upper airway symptoms recorded. In patients with asthma, nNO was
      positively correlated with exhaled NO, bronchial responsiveness and asthma
      control. This study suggests clinical utility of nNO in subjects with asthma, but
      in order to get better understanding of the nNO determinants, simultaneous
      mapping of upper airway comorbidities by clinical examination is appropriate. 

PMID- 24675000
TI  - Pulmonary hypertension and noncardiac surgery: implications for the
      anesthesiologist.

PMID- 24675001
TI  - Diastolic dysfunction in patients undergoing cardiac surgery: the role of gender
      and age-gender interaction.
AB  - OBJECTIVES: To test the hypothesis that females presenting for coronary artery
      bypass graft (CABG) surgery are at a higher risk of left ventricular diastolic
      dysfunction (LVDD) and that age and gender interact to influence this risk.
      DESIGN: Retrospective observational study. SETTING: Tertiary university hospital.
      PARTICIPANTS: Eight hundred-ninety-five adult patients undergoing CABG surgery.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline diastolic function
      was graded according to a predefined Doppler-based algorithm, which defined LVDD
      as a binary variable (grades 2 and 3 only) and as a continuous variable (E/e'
      ratio). The authors found that women were more likely to present with LVDD in 2
      multivariate regression models using both LVDD definitions (odds ratio = 2.7;
      p<0.0001 for logistic model, and parameter estimate (PE) = 2.8; p<0.0001 for the
      linear model). In addition, there was a significant age and gender interaction on
      the risk of LVDD in the linear model (PE = 0.08; p = 0.01). A restricted cubic
      splines analysis revealed a progressively higher risk of LVDD (predicted E/e'
      ratio) among older women. CONCLUSIONS: The authors confirmed that women
      undergoing CABG surgery are at higher risk of LVDD compared to men with a
      significant age-gender interaction suggesting a possible age-related differential
      effect on LVDD between the genders, a phenomenon previously demonstrated in
      preclinical studies. Therapies aimed at amelioration of diastolic dysfunction
      additionally should consider the higher risk in females, especially within the
      older subset of the patient population.

PMID- 24675002
TI  - Urgent living donor liver transplantation for biliary atresia complicated by a
      strangulated internal hernia at Roux-en Y limb: a case report.
AB  - BACKGROUND: When BA patients with end-stage liver dysfunction have bowel
      obstruction, especially strangulated internal hernia, selecting optimal surgical
      therapeutic options is crucial. CASE REPORT: An 11-month-old female with end
      stage biliary atresia (BA) was admitted for a strangulated internal hernia at the
      Roux-en Y limb and frequent episodes of gastrointestinal bleeding requiring blood
      transfusion. She was scheduled within a month to receive a portion of the liver
      from her blood-type identical mother. Despite intensive care, her clinical
      condition obviously needed a prompt surgical intervention. The operative findings
      at laparotomy revealed exudative moderate ascites and a dilated and ischemic
      afferent loop that was strangulated by a band extending from the mesentery to the
      transverse mesocolon. The attachment of the band was released, and gangrenous
      changes were recognized in the incarcerated bowel, although there were no obvious
      findings of intestinal perforation. After the gangrenous afferent loop was
      resected, the remnant afferent loop was too short to anastomose again. Following
      these procedures, as the patient's vital signs remained stable, we decided to
      simultaneously perform living donor liver transplantation (LDLT). She
      successfully underwent LDLT and her post-transplant course was uneventful.
      CONCLUSIONS: When faced with candidates for LT as an urgent life-saving surgery,
      determining whether LDLT should be performed simultaneously during perioperative
      management is necessary to save the life of the patient.

PMID- 24675003
TI  - Validation of remote mapping of cochlear implants.
AB  - Recipients of cochlear implants need to attend regular mapping sessions to adjust
      their speech processors. We developed a PC-based system for remote mapping, which
      employed voice, video and text communication. Eleven implant recipients had their
      implant electrodes programmed (mapped) both by conventional methods and remotely.
      Speech tests, conducted by a family member or research assistant, were used to
      test the outcome of the programming during the remote consultation. The recipient
      and audiologist were surveyed regarding aspects of the teleconsultation. There
      were no significant differences between conventionally and remotely programmed
      electrode settings. The speech test results were perfect in most cases. The
      average time to complete the conventional mapping session was 37 min and the
      average time for the remote mapping session was 42 min (P = 0.034). Recipients
      and the audiologist reported favourably on most aspects of the consultations.
      Lack of synchronisation between voice and video was the most common problem,
      which disrupted communication. The assistant was important to overcome this
      problem. All but one participant indicated they would be willing to use tele
      mapping in the future. Remote programming of cochlear implants can be conducted
      reliably with relatively simple equipment, potentially in the homes of remotely
      located patients assisted by a family member.

PMID- 24675004
TI  - Epicardial fat, rather than pericardial fat, is independently associated with
      diastolic filling in subjects without apparent heart disease.
AB  - BACKGROUND AND AIM: Epicardial and pericardial fat are separate fat depots
      surrounding the heart. Previous studies found epicardial fat to be associated
      with diastolic dysfunction, but they had some limitations. Pericardial fat
      association with diastolic dysfunction was not examined. Our aim was to assess
      the relation of epicardial and pericardial fat with diastolic filling. METHODS
      AND RESULTS: In 73 volunteers without known heart disease or complaints, using
      echocardiography, we measured epicardial and pericardial fat thickness from
      long(LAX) and short(SAX) axis views and assessed diastolic filling: mitral inflow
      (E/A ratio, E wave deceleration time[DT]), pulmonary vein flow
      (systolic/diastolic ratio [S/D], systolic filling fraction[SFR], late retrograde
      velocity[Ar]), color M-mode flow propagation velocity [Vp], and tissue Doppler
      derived mitral early annular velocities at the septum [e' sep] and lateral wall
      [e'-lat]. By Spearman's correlation, epicardial fat from LAX had a weak, but
      statistically significant correlations with several diastolic filling indices
      (SFR{rs = 0.29, P = 0.02}, Ar{rs = 0.3, P = 0.01}, Vp{rs = -0.3, P = 0.01}, e'
      sep{rs = -0.23, P = 0.04}, e' lat{rs = -0.26, P = 0.03}). In multivariate
      logistic regression model adjusting for age, gender, diabetes, systolic blood
      pressure and left ventricle mass index, epicardial fat thickness from LAX (and
      not from SAX) was the only independent predictor of e' [e' sep < 8: OR = 1.8,
      95%CI = 1.1-2.9; e' lat<10: OR = 1.6, 95%CI = 1.01-2.6]. After adjustment,
      Pericardial fat measured from LAX was independent predictor of e' lat only[e' lat
      < 10:OR = 1.3, 95% CI 1.03-1.6). CONCLUSIONS: Epicardial fat measured from LAX is
      an independent predictor of myocardial relaxation. Pericardial fat independent
      association with diastolic filling is uncertain.

PMID- 24675005
TI  - Serum uric acid and its relationship with metabolic syndrome and cardiovascular
      risk profile in patients with hypertension: insights from the I-DEMAND study.
AB  - BACKGROUND AND AIMS: The independent role of serum uric acid (SUA) as a marker of
      cardio-renal risk is debated. The aim of this study was to assess the
      relationship between SUA, metabolic syndrome (MS), and other cardiovascular (CV)
      risk factors in an Italian population of hypertensive patients with a high
      prevalence of diabetes. METHODS AND RESULTS: A total of 2429 patients (mean age
      62 +/- 11 years) among those enrolled in the I-DEMAND study were stratified on
      the basis of SUA gender specific quartiles. MS was defined according to the NCEP
      ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60
      ml/min/1.73 m(2) or as the presence of microalbuminuria (albumin-to-creatinine
      ratio >=2.5 mg/mmol in men and >=3.5 mg/mmol in women). The prevalence of MS,
      CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA
      levels correlated with the presence of MS, its components, signs of renal damage
      and worse CV risk profile. Multivariate logistic regression analysis revealed
      that SUA was associated with a positive history of CV events and high Framingham
      risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03
      1.18; P = 0.0060; OR 1.28, 95% CI 1.15-1.42; P < 0.0001). These associations were
      stronger in patients without diabetes and with normal renal function.
      CONCLUSIONS: Mild hyperuricemia is a strong, independent marker of MS and high
      cardio-renal risk profile in hypertensive patients under specialist care.
      Intervention trials are needed to investigate whether the reduction of SUA levels
      favorably impacts outcome in patients at high CV risk.

PMID- 24675007
TI  - Definition of renal glomerular hyperfiltration or hypofiltration from the
      reference population.

PMID- 24675006
TI  - PPARalpha gene polymorphisms modulate the association between physical activity
      and cardiometabolic risk.
AB  - BACKGROUND AND AIMS: Habitual physical activity is understood to help prevent
      type 2 diabetes and atherosclerotic cardiovascular disease via beneficial effects
      on both metabolism and the vascular system. However, individuals do not have
      uniform cardiometabolic responses to physical activity. Here we explore the
      extent to which variation in the proliferator-activated receptor-alpha
      (PPARalpha) gene, which modulates carbohydrate and lipid metabolism, vascular
      function, and inflammation, predicts the overall cardiometabolic risk (CMR)
      profile of individuals engaging in various levels of physical activity. METHODS
      AND RESULTS: 917 unrelated, community volunteers (52% female, of Non-Hispanic
      European ancestry) aged 30-54 years, participated in the cross-sectional study.
      Subjects were genotyped for 5 single nucleotide polymorphisms in the PPARalpha
      gene, from which common haplotypes were defined. A continuous measure of CMR was
      calculated as an aggregate of 5 traditional risk factors: waist circumference,
      resting blood pressure, fasting serum triglycerides, HDL-cholesterol and glucose.
      Regression models were used to examine the main and interactive effects of
      physical activity and genetic variation on CMR. One common PPARalpha haplotype (H
      23) was associated with a higher CMR. This association was moderated by daily
      physical activity (B = -0.11, SE = 0.053, t = -2.05, P = 0.04). Increased
      physical activity was associated with a steeper reduction of CMR in persons
      carrying the otherwise detrimental H-23 haplotype. CONCLUSIONS: Variations in the
      PPARalpha gene appear to magnify the cardiometabolic benefits of habitual
      physical activity.

PMID- 24675008
TI  - Relationships between mild hyperuricaemia and aortic stiffness in untreated
      hypertensive patients.
AB  - BACKGROUND AND AIMS: Clinical studies exploring the relationship between serum
      uric acid (SUA) and arterial stiffness yielded conflicting results. Only in a few
      of these studies, arterial distensibility was examined by measuring aortic pulse
      wave velocity (PWV), which is considered the gold standard for evaluating
      arterial stiffness. In none of the previous investigations was the influence of
      SUA on aortic distensibility assessed, taking into account the effect of
      albuminuria. The purpose of our study was to comprehensively analyse the
      relationships between SUA and aortic PWV in a group of essential hypertensive
      patients. METHODS AND RESULTS: We enrolled 222 untreated and uncomplicated
      hypertensive subjects (mean age: 44 +/- 10 years; 60% males), without gout. In
      all patients, SUA and urinary albumin excretion rate (AER) were determined.
      Moreover, carotid-femoral (c-f) PWV was measured. C-f PWV was significantly
      higher in hypertensive patients belonging to the uppermost tertile of SUA
      distribution, compared to subjects of the lowest tertiles (10.9 +/- 2.2 vs. 10 +/
      1.8 vs. 9.9 +/- 1.7 m s(-1); p = 0.001). In univariate analysis, SUA correlated
      with c-f PWV (r = 0.24; p < 0.001). This association disappeared when AER was
      added in a multiple regression model, including SUA, age, mean arterial pressure,
      gender, metabolic syndrome components and glomerular filtration rate. CONCLUSION:
      The results of our study showed that, in essential hypertensive subjects, there
      is a positive relationship between mild hyperuricaemia and aortic stiffness. This
      association weakened after adjustment for covariates and lost statistical
      significance after further correction for albuminuria.

PMID- 24675009
TI  - Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub
      Saharan African adults.
AB  - BACKGROUND AND AIMS: Simple, low-cost central obesity measures may help identify
      individuals with increased cardiometabolic disease risk, although it is unclear
      which measures perform best in African adults. We aimed to: 1) cross-sectionally
      compare the accuracy of existing waist-to-height ratio (WHtR) and waist
      circumference (WC) thresholds to identify individuals with hypertension, pre
      diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect
      CVD risk in this African population; and 3) assess which measure best predicts 5
      year CVD risk. METHODS AND RESULTS: Black South Africans (577 men, 942 women,
      aged >30years) were recruited by random household selection from four North West
      Province communities. Demographic and anthropometric measures were taken.
      Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR >
      0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and
      glycated haemoglobin measured at baseline and 5 year follow up. Women were
      significantly more overweight than men at baseline (mean body mass index (BMI)
      women 27.3 +/- 7.4 kg/m(2), men 20.9 +/- 4.3 kg/m(2)); median WC women 81.9 cm
      (interquartile range 61-103), men 74.7 cm (63-87 cm), all P < 0.001). In women,
      both WC and WHtR significantly predicted all cardiometabolic risk factors after 5
      years. In men, even after adjusting WC threshold based on ROC analysis, WHtR
      better predicted overall 5-year risk. Neither measure predicted hypertension in
      men. CONCLUSIONS: The WHtR threshold of >0.5 appears to be more consistently
      supported and may provide a better predictor of future cardiometabolic risk in
      sub-Saharan Africa.

PMID- 24675010
TI  - The effect of green tea on blood pressure and lipid profile: a systematic review
      and meta-analysis of randomized clinical trials.
AB  - INTRODUCTION: Many different dietary supplements are currently marketed for the
      management of hypertension, but the evidence for effectiveness is mixed. The aim
      of this systematic review was to evaluate the evidence for or against the
      effectiveness of green tea (Camellia sinensis) on blood pressure and lipid
      parameters. METHODS AND RESULTS: Electronic searches were conducted in Medline,
      Embase, Amed, Cinahl and the Cochrane Library to identify relevant human
      randomized clinical trials (RCTs). Hand searches of bibliographies were also
      conducted. The reporting quality of included studies was assessed using a
      checklist adapted from the CONSORT Statement. Two reviewers independently
      determined eligibility, assessed the reporting quality of the included studies,
      and extracted the data. As many as 474 citations were identified and 20 RCTs
      comprising 1536 participants were included. There were variations in the designs
      of the RCTs. A meta-analysis revealed a significant reduction in systolic blood
      pressure favouring green tea (MD: -1.94 mmHg; 95% CI: -2.95 to -0.93; I(2) = 8%;
      p = 0.0002). Similar results were also observed for total cholesterol (MD: -0.13
      mmol/l; 95% CI: -0.2 to -0.07; I(2) = 8%; p < 0.0001) and LDL cholesterol (MD: 
      0.19 mmol/l; 95% CI: -0.3 to -0.09; I(2) = 70%; p = 0.0004). Adverse events
      included rash, elevated blood pressure, and abdominal discomfort. CONCLUSION:
      Green tea intake results in significant reductions in systolic blood pressure,
      total cholesterol, and LDL cholesterol. The effect size on systolic blood
      pressure is small, but the effects on total and LDL cholesterol appear moderate.
      Longer-term independent clinical trials evaluating the effects of green tea are
      warranted.

PMID- 24675012
TI  - Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and
      mTOR: findings from 3-D melanoma skin equivalents and computational modeling.
AB  - The incidence of melanoma continues to rise. Inspite of treatment advances, the
      prognosis remains grim once the disease has metastasized, emphasizing the need to
      explore additional therapeutic strategies. One such approach is through the use
      of mechanism-based dietary intervention. We previously showed that the flavonoid
      fisetin inhibits melanoma cell proliferation, in vitro and in vivo. Here, we
      studied fisetin-mediated regulation of kinases involved in melanoma growth and
      progression. Time-course analysis in 3-D melanoma constructs that transitioned
      from radial to vertical growth showed that fisetin treatment resulted in
      significant decrease in melanocytic lesions in contrast to untreated controls
      that showed large tumor nests and invading disseminated cells. Further studies in
      melanoma cultures and mouse xenografts showed that fisetin-mediated growth
      inhibition was associated with dephosphorylation of AKT, mTOR and p70S6K
      proteins. In silico modeling indicated direct interaction of fisetin with mTOR
      and p70S6K with favorable free energy values. These findings were validated by
      cell-free competition assays that established binding of fisetin to p70S6K and
      mTOR while little affinity was detected with AKT. Kinase activity studies
      reflected similar trend with % inhibition observed for p70S6K and mTOR at lower
      doses than AKT. Our studies characterized, for the first time, the differential
      interactions of any botanical agent with kinases involved in melanoma growth and
      demonstrate that fisetin inhibits mTOR and p70S6K through direct binding while
      the observed inhibitory effect of fisetin on AKT is mediated indirectly, through
      targeting interrelated pathways. 

PMID- 24675014
TI  - A multi-centre randomised controlled trial of Transfusion Indication Threshold
      Reduction on transfusion rates, morbidity and healthcare resource use following
      cardiac surgery: study protocol.
AB  - Thresholds for red blood cell transfusion following cardiac surgery vary by
      hospital and surgeon. The TITRe2 multi-centre randomised controlled trial aims to
      randomise 2000 patients from 17 United Kingdom centres, and tests the hypothesis
      that a restrictive transfusion threshold will reduce postoperative morbidity and
      health service costs compared to a liberal threshold. Patients consent to take
      part in the study pre-operatively but are only randomised if their haemoglobin
      falls below 9 g/dL during their post-operative hospital stay. The primary outcome
      is a binary composite outcome of any serious infectious or ischaemic event in the
      first three months after randomisation. Many challenges have been encountered in
      the set-up and running of the study.

PMID- 24675016
TI  - Parimagnetism in HoCo2 and TmCo2.
AB  - X-ray magnetic circular dichroism (XMCD), longitudinal (chiac) and transverse
      (TS) ac magnetic susceptibility have been measured in the RCo2 series (R = Ho,
      and Tm) as a function of temperature and applied magnetic field. We show that
      parimagnetism is a general behavior among the RCo2 ferrimagnetic series (R being
      a heavy rare-earth ion). XMCD results supply evidence of the presence of two
      compensation temperatures above Tc, defining two different parimagnetic
      configurations, which is a fully unexpected result. The inverse chi'ac curve
      exhibits a small anomaly which vanishes under low applied magnetic fields. The
      combination of TS and XMCD measurements allows one to depict new magnetic phase
      diagrams for these compounds of the RCo2 series. A new scenario allowing one to
      understand the observed phenomenology as a Griffiths phase-like behavior is
      proposed, where the amorphous RCo2 represents the undiluted system case.

PMID- 24675015
TI  - Seroprevalence of cytomegalovirus antibodies among blood donors and
      Multitransfused recipients--a study from north India.
AB  - BACKGROUND AND OBJECTIVES: Primary Cytomegalovirus infection caused by
      transfusion is a major problem for immunocompromised CMV seronegative patients.
      Documentation of the status of antibodies to cytomegalovirus in the blood donor
      pool population is vital to the understanding of the potential likelihood of
      transmission through donor blood and for determining the best transfusion
      practices to prevent TT-CMV infection. The present study was conducted to
      determine the prevalence of CMV infection among blood donors and Multitransfused
      recipients of north Indian population. MATERIAL AND METHODS: A prospective study
      was done on 2100 donors' samples and 200 patients sample for CMV antibodies using
      the ELISA technique. RESULTS: Out of 2100 donors recruited, 93.8% males and 6.2%
      females. 98.6% were positive for anti CMV IgG antibodies and only one donor was
      positive for anti CMV IgM antibody. In Multitransfused patients, out of 200
      patients, seroprevalence for anti CMV IgG antibodies was in 100% patients and
      only one patient was positive for anti CMV IgM antibody. CONCLUSION: The study
      did not demonstrate statistical significant influence of age and gender on
      prevalence of anti CMV IgG and IgM antibodies. Other preventive strategies such
      as universal leucodepletion may be implemented to prevent transmission of CMV in
      immunocompromised patients.

PMID- 24675017
TI  - Medicine at the limits of evidence: the fundamental limitation of the randomized
      clinical trial and the end of equipoise.

PMID- 24675019
TI  - Congenital infantile fibrosarcoma.

PMID- 24675018
TI  - Alveolar capillary dysplasia with multiple congenital anomalies and bronchoscopic
      airway abnormalities.
AB  - Alveolar capillary dysplasia is a rare and fatal disease of newborn infants. Here
      we describe a patient with alveolar capillary dysplasia, multiple congenital
      anomalies, a novel genetic mutation and previously undocumented airway findings
      on bronchoscopy. Knowledge of these associations may help diagnose this rare
      disorder in neonates with hypoxemic respiratory failure. 

PMID- 24675020
TI  - Technical tip: tightrope fixation of neer type II distal clavicle fracture
      supported by a case series.
AB  - BACKGROUND: We present a case series of 3 patients who underwent a novel
      technique of tight rope fixation for Neer type II distal clavicle fracture.
      MATERIAL AND METHODS: 2-3 cm incision was made lateral to the fracture site
      moving inferomedially. Part of the distal end of clavicle was exposed close to
      fracture site and further dissection was carried out to reveal the coracoid
      process. Tight rope fixation of the distal ends of clavicle and coracoid was
      performed to achieve satisfactory fracture reduction on x-ray. RESULTS: 4 weeks
      of sling with gentle pendulum movement were followed by active shoulder movement
      exercises. Radiographic union was reached at 6 weeks' time, while the patients
      achieved proper shoulder functionality 3 months following the operation.
      CONCLUSIONS: Neer type II distal clavicle fractures are characterized by
      disruption of the coracoclavicular ligament with wide proximal fragment
      displacement. Overall, type II distal clavicle fractures have a 20-30% nonunion
      rate if treated non-surgically. Various techniques have been described for the
      treatment of these fractures, including hook plate and nailing. Tight rope
      fixation provides proper apposition of the fracture fragments for union by
      maintaining a reduced coracoclavicular interval.

PMID- 24675022
TI  - Simultaneous re-isolation of the left pulmonary veins and termination of peri
      mitral flutter with only an ethanol infusion in the vein of Marshall: killing two
      birds with one stone.

PMID- 24675021
TI  - Refined diagnostic criteria and classification of mast cell leukemia (MCL) and
      myelomastocytic leukemia (MML): a consensus proposal.
AB  - Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis
      (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the
      bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of
      patients, circulating MCs are detectable. A major differential diagnosis to MCL
      is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have
      been published, several questions remain concerning terminologies and
      subvariants. To discuss open issues, the EU/US-consensus group and the European
      Competence Network on Mastocytosis (ECNM) launched a series of meetings and
      workshops in 2011-2013. Resulting discussions and outcomes are provided in this
      article. The group recommends that MML be recognized as a distinct condition
      defined by mastocytic differentiation in advanced myeloid neoplasms without
      evidence of SM. The group also proposes that MCL be divided into acute MCL and
      chronic MCL, based on the presence or absence of C-Findings. In addition, a
      primary (de novo) form of MCL should be separated from secondary MCL that
      typically develops in the presence of a known antecedent MC neoplasm, usually
      aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also
      proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in
      BM smears, which is generally accepted to be of prognostic significance. We
      recommend that this condition be termed ASM in transformation to MCL (ASM-t). The
      refined classification of MCL fits within and extends the current WHO
      classification; and should improve prognostication and patient selection in
      practice as well as in clinical trials. 

PMID- 24675023
TI  - Mutation models for DVI analysis.
AB  - In recent years, the use of DNA data for personal identification has become a
      crucial feature for forensic applications such as disaster victim identification
      (DVI). Computational methods to cope with these kinds of problems must be
      designed to handle large scale events with a high number of victims, obtaining
      likelihood ratios and posterior odds with respect to different identification
      hypotheses. Trying to minimize identification error rates (i.e., false negatives
      and false positives), a number of computational methods, based either on the
      choice between alternative mutation models or on the adoption of a different
      strategy, are proposed and evaluated. Using simulation of DNA profiles, our goal
      is to suggest which is the most appropriate way to address likelihood ratio
      computation in DVI cases, especially to be able to efficiently deal with
      complicating issues such as mutations or null alleles, considering that data
      about these latter are limited and fragmentary. 

PMID- 24675024
TI  - Trypanosoma cruzi persistence in the native heart is associated with high-grade
      myocarditis, but not with Chagas' disease reactivation after heart
      transplantation.
AB  - BACKGROUND: Chagas' disease reactivation (CDR) after heart transplantation (HTx)
      is characterized by relapse of the infectious disease, with direct detection of
      Trypanosoma cruzi parasites in blood, cerebrospinal fluid, or tissues. We
      investigated whether a detailed pathologic examination of the explanted heart at
      HTx with evaluation of myocarditis and parasitic persistence or load in the
      myocardium could be useful to identify patients at high risk of CDR. METHODS: The
      native hearts of 18 chagasic patients who presented CDR after HTx (CDR+ group)
      were compared with the native hearts of 16 chagasic patients who never presented
      CDR in a follow-up of at least 18 months after HTx (CDR- group). The intensity of
      myocarditis was evaluated semiquantitatively. Parasite persistence/load in the
      myocardium was investigated through immunohistochemistry for T cruzi antigens and
      by qualitative and quantitative real-time PCR for T cruzi DNA. RESULTS: The rate
      of high-grade myocarditis, parasite persistence, and the median of parasitic load
      and parasitic load/10(6) cells in the CDR+ group were 83.3%, 77.8%, 8.43 * 10(
      3), and 9.890, respectively, whereas in the CDR- group the values were 87.5%,
      50%, 7.49*10(-3), and 17.800. There was no statistical difference between the
      groups. High-grade myocarditis was present in all 22 samples (100%) with parasite
      persistence and in 7 of 12 samples (58.3%) with no parasite persistence (p =
      0.003). CONCLUSIONS: Although associated with high-grade myocarditis, T cruzi
      parasite persistence in the myocardium of the native heart is not associated with
      the occurrence of CDR after HTx.

PMID- 24675025
TI  - Bidirectional crosstalk between periventricular endothelial cells and neural
      progenitor cells promotes the formation of a neurovascular unit.
AB  - Interactions between neural progenitor cells (NPC) and endothelial cells (EC)
      from adult vascular beds have been well explored previously. However, the factors
      and signaling mechanisms that regulate neurogenesis and angiogenesis are most
      prevalent during embryonic development. This study aimed to determine whether
      embryonic brain endothelial cells from the periventricular region (PVEC) present
      an advantage over adult brain EC in supporting NPC growth and differentiation.
      PVEC were isolated from E15 mouse brains, processed, and sorted with
      immunomagnetic beads using antibodies against CD31/PECAM. On immunofluorescence
      (IF) staining, nearly all cells were positive for EC markers CD31 and CD144/VE
      Cadherin. In proliferation studies, NPC proliferation was highest in transwell co
      culture with PVEC, approximately 2.3 fold increase compared to baseline versus
      1.4 fold increase when co-cultured with adult brain endothelial cells (ABEC).
      These results correlated with the PVEC mediated delay in NPC differentiation,
      evidenced by high expression of progenitor marker Nestin evaluated by IF
      staining. Upon further characterization of PVEC in an angiogenesis assay
      measuring cord length, PVEC exhibited a high capacity to form cords in basal
      conditions compared to ABEC. This was enhanced in the presence of NPC, with both
      cell types displaying a preferential structural alignment resembling
      neurovascular networks. PVEC also expressed high Vegfa levels at baseline in
      comparison to NPC and ABEC. Vegfa levels increased when co-cultured with NPC. We
      demonstrate that PVEC and NPC co-cultures act synergistically to promote the
      formation of a neurovascular unit through dynamic and reciprocal communication.
      Our results suggest that PVEC/NPC could provide promising neuro-regenerative
      therapies for patients suffering brain injuries. 

PMID- 24675026
TI  - Altered default mode and fronto-parietal network subsystems in patients with
      schizophrenia and their unaffected siblings.
AB  - The complex symptoms of schizophrenia have recently been linked to disrupted
      neural circuits and corresponding malfunction of two higher-order intrinsic brain
      networks: The default mode network (DMN) and the fronto-parietal network (FPN).
      These networks are both functionally heterogeneous and consist of multiple
      subsystems. However, the extent to which these subsystems make differential
      contributions to disorder symptoms and to what degree such abnormalities occur in
      unaffected siblings have yet to be clarified. We used resting-state functional
      MRI (rs-fMRI) to examine group differences in intra- and inter-connectivity of
      subsystems within the two neural networks, across a sample of patients with
      schizophrenia (n=24), their unaffected siblings (n=25), and healthy controls
      (n=22). We used group independent component analysis (gICA) to identify four
      network subsystems, including anterior and posterior portions of the DMN (aDMN,
      pDMN) as well as left- and right-lateralized portions of the FPN (lFPN, rFPN).
      Intra-connectivity is defined as neural coherence within a subsystem whereas
      inter-connectivity refers to functional connectivity between subsystems. In terms
      of intra-connectivity, patients and siblings shared dysconnection within the aDMN
      and two FPN subsystems, while both groups preserved connectivity within the pDMN.
      In terms of inter-connectivity, all groups exhibited positive connections between
      FPN and DMN subsystems, with patients having even stronger interaction between
      rFPN and aDMN than the controls, a feature that may underlie their psychotic
      symptoms. Our results implicate that DMN subsystems exhibit different liabilities
      to the disease risk while FPN subsystems demonstrate distinct inter-connectivity
      alterations. These dissociating manners between network subsystems explicitly
      suggest their differentiating roles to the disease susceptibility and
      manifestation. 

PMID- 24675027
TI  - t-PA, but not desmoteplase, induces plasmin-dependent opening of a blood-brain
      barrier model under normoxic and ischaemic conditions.
AB  - Tissue-type plasminogen activator (t-PA) is the only thrombolytic treatment
      available for patients with acute ischaemic stroke. However, t-PA can increase
      permeability of the blood-brain barrier (BBB). Desmoteplase is a plasminogen
      activator derived from the common vampire bat, currently under clinical
      development for ischaemic stroke. We compared how t-PA and desmoteplase
      influenced BBB permeability using a human in vitro model where primary brain
      endothelial cells (BEC) and astrocytes are co-cultured on the opposite sides of a
      porous membrane. Permeability changes were evaluated 6 or 24h post-stimulation by
      passage of fluorescent albumin across the membrane. Under normoxic conditions, t
      PA, but not desmoteplase, increased BBB permeability. Surprisingly, the ability
      of t-PA to affect the barrier was lost under conditions of oxygen-glucose
      deprivation (OGD). Addition of plasminogen re-sensitised the BBB to the action of
      t-PA under both normoxia and OGD, but did not affect the inert behaviour of
      desmoteplase, even when digested fibrinogen was added to ensure optimal plasmin
      generation. These observations coincided with plasmin-dependent changes in
      astrocyte and BEC morphology and disruption of tight junction proteins in BECs,
      specifically initiated by t-PA but not by desmoteplase. Finally, inhibition of
      plasmin post-stimulation with t-PA and plasminogen, especially within 2h,
      protected the BBB against t-PA-mediated barrier opening. Hence t-PA, but not
      desmoteplase, increases BBB permeability under both normoxic and OGD conditions
      in a reversible, plasmin-dependent process. The inability of desmoteplase to
      increase permeability despite its capacity to generate plasmin provides further
      support for its use as thrombolytic in patients with ischaemic stroke. 

PMID- 24675028
TI  - Neuroprotective effects of compound FLZ in an ischemic model mediated by
      improving cerebral blood flow and enhancing Hsp27 expression.
AB  - Compound FLZ is a synthetic novel derivate of natural squamosamide, which has
      potent neuroprotective effects based on our previous study. We are now aiming to
      investigate the effects of FLZ on cerebral blood flow (CBF), infarct volume,
      neurological function, heat shock protein 70 (Hsp70), and Hsp27 expression in
      transient focal ischemia. For this goal, an animal model of middle cerebral
      artery occlusion (MCAO) for 2h followed by reperfusion was used, and animals
      received low or high doses of FLZ (150 or 300mg/kg), orally 10min after MCAO
      onset. The results show that the infarct volume was 32.7% for the vehicle control
      group, and reduced to 17.6 and 12.8% for the low and high dose FLZ-treated
      groups, respectively. FLZ treatment also significantly improved the
      neurobehavioral score from 2.6 in the vehicle control group to 1.0 and 0.9 in the
      low and high dose groups, respectively. Further, FLZ significantly induced Hsp27
      over-expression and reduced over-expression of HSP70, a sensitive marker of acute
      ischemia, in ipsilateral cortex by a dose-dependent manner. In addition, CBF was
      quantified using laser-Doppler flowmetry. During ischemia, regional CBF (rCBF)
      was improved from approximately 30% to over 50% of the baseline and the
      reperfusion-induced hyperemia was reduced in both FLZ dosage groups.
      Particularly, high dose FLZ reduced rCBF during hyperemia by 30%. In conclusion,
      FLZ (150 and 300mg/kg) can significantly reduce the infarct volume and improve
      neurobehavioral deficits in a rat MCAO model, most likely through improving CBF
      in the penumbra and enhancing Hsp27 expression.

PMID- 24675029
TI  - Ischemic preconditioning enhances autophagy but suppresses autophagic cell death
      in rat spinal neurons following ischemia-reperfusion.
AB  - Autophagy serves to eliminate damaged proteins and organelles under normal
      physiological conditions and can be accelerated by pathological stress, possibly
      as a cytoprotective mechanism. Brief periods of ischemia (ischemic
      preconditioning or IPC) can reduce neuronal death in response to subsequent
      severe ischemic insults. Ischemic preconditioning also induces autophagy, but the
      contribution of autophagy to IPC-associated neuroprotection remains unclear. We
      investigated the contribution of autophagy to IPC-mediated neuroprotection in
      rats subjected to ischemic spinal cord injury. Fifty adult rats were randomly
      assigned to either (1) a sham group receiving anesthesia and surgical preparation
      (n=5), (2) an ischemia/reperfusion (I/R) group (n=20) subjected to 0.5 h ischemia
      followed by 3, 6, 12, or 24 h reperfusion, (3) an IPC group receiving three
      cycles of 5 min ischemia followed by 5 min of reperfusion (n=5), or (4) an
      IPC+I/R group (n=20). Hematoxylin-eosin (HE) and immunohistochemical staining
      were performed to evaluate spinal neuron survival in the four treatment groups.
      Autophagic activity was investigated by electron microscopy and by
      immunohistochemical and Western blot analyses of the autophagosome marker LC3-II
      and the autophagy-associated BH3 protein Beclin-1. Changes in Bcl-2/Beclin-1
      complex association and Bcl-2 phosphorylation (p-Bcl-2) were examined by co
      immunoprecipitation and Western blot analyses. In the I/R group, LC3-II was
      significantly elevated after 3h of reperfusion, but declined significantly by 24
      h. At 24 h, I/R rats exhibited extensive spinal damage and decreased neuronal
      survival. In the IPC+IR group, neuronal death was reduced and expression of LC3
      II sustained throughout the 24 h reperfusion period. In the I/R group, expression
      of (inactive) p-Bcl-2(Ser70) was increased significantly during reperfusion and
      was accompanied by dissociation of the Bcl-2/Beclin-1 complex and increased
      Beclin-1 expression. Preconditioning inhibited these changes in p-Bcl-2, Beclin
      1, and Bcl-2/Beclin-1 complex expression. Ischemic preconditioning appears to
      sustain the beneficial effects of autophagic lysosomal degradation during I/R
      while inhibiting autophagic cell death.

PMID- 24675030
TI  - Overexpressing neuroglobin improves functional recovery by inhibiting neuronal
      apoptosis after spinal cord injury.
AB  - The current study was performed to evaluate the mechanisms and therapeutic
      effects of overexpressing neuroglobin (Ngb) on spinal cord injury (SCI). Adeno
      associated virus (AAV) was injected in the T12 section 7 days before SCI. Animals
      were randomly divided into four groups: a sham group, a vehicle group, an AAV
      EGFP group and an AAV-Ngb group. Recovery of hind limb locomotor function was
      determined during the 3-week post operation period by the Basso, Beattie and
      Bresnahan locomotor rating scale. At 24 h after SCI and at the end of the study,
      the segments of spinal cord, centered with the lesion site were harvested for
      histopathological analysis. Immunofluorescence was performed using antibodies to
      recognize neuN in the lesion sections. At 24 h after SCI, the spinal cord tissue
      samples were removed to analyze tissue concentrations of superoxide dismutase
      (SOD) and malondialdehyde (MDA). Apoptotic cells were assessed using a terminal
      deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) kit. The expression
      of bcl-2, bax, cytochrome c, and cleaved caspase-3, were determined by Western
      blot assay and immunostaining analysis. The results showed that animals
      overexpressing Ngb had significantly greater recovery of locomotor function, less
      neuronal loss and fewer apoptotic cells. In addition, overexpressing Ngb
      significantly increased bcl-2 expression and SOD level, decreased bax expression,
      attenuated the release of cytochrome c from mitochondria to the cytosol fraction,
      and reduced the activity of caspase-3 and MDA level after SCI. These findings
      suggest, that overexpressing Ngb can significantly improve the recovery of
      locomotor function. This neuroprotective effect may be associated with the
      inhibition of neural apoptosis via the mitochondrial pathway.

PMID- 24675031
TI  - Central antinociception induced by ketamine is mediated by endogenous opioids and
      MU- and delta-opioid receptors.
AB  - It is generally believed that NMDA receptor antagonism accounts for most of the
      anesthetic and analgesic effects of ketamine, however, it interacts at multiple
      sites in the central nervous system, including NMDA and non-NMDA glutamate
      receptors, nicotinic and muscarinic cholinergic receptors, and adrenergic and
      opioid receptors. Interestingly, it was shown that at supraspinal sites, ketamine
      interacts with the MU-opioid system and causes supraspinal antinociception. In
      this study, we investigated the involvement of endogenous opioids in ketamine
      induced central antinociception. The nociceptive threshold for thermal
      stimulation was measured in Swiss mice using the tail-flick test. The drugs were
      administered via the intracerebroventricular route. Our results demonstrated that
      the opioid receptor antagonist naloxone, the MU-opioid receptor antagonist
      clocinnamox and the delta-opioid receptor antagonist naltrindole, but not the
      kappa-opioid receptor antagonist nor-binaltorphimine, antagonized ketamine
      induced central antinociception in a dose-dependent manner. Additionally, the
      administration of the aminopeptidase inhibitor bestatin significantly enhanced
      low-dose ketamine-induced central antinociception. These data provide evidence
      for the involvement of endogenous opioids and MU- and delta-opioid receptors in
      ketamine-induced central antinociception. In contrast, kappa-opioid receptors not
      appear to be involved in this effect. 

PMID- 24675032
TI  - Childhood environments and cytomegalovirus serostatus and reactivation in adults.
AB  - Childhood adversity, defined in terms of material hardship or physical or
      emotional maltreatment has been associated with risk for infection with
      cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation
      in children and adults. The present study examined whether different dimensions
      of childhood experience-those pertaining to socioeconomic status (SES), physical
      environment, or family relationships-relate differentially to CMV serostatus and
      reactivation during adulthood. Participants were 140 healthy adults, aged 18
      55years (41% female; 64% white). Childhood environments were assessed
      retrospectively and included family SES (parental housing tenure); childhood
      neighborhood environment (urban residence; physical conditions; safety; and
      social atmosphere); residential exposures (parental smoking and physical
      condition of home); and family relationships (parental divorce; warmth; harmony;
      dysfunction; parental bonding). Approximately 39% (n=53) of participants were
      CMV+. In individual analyses controlling for age, sex, race, body mass, current
      adult SES and smoking status, fewer years of parental home ownership, having a
      parent who smoked, and living in a poorly maintained or unsafe neighborhood each
      were associated with greater odds of infection with CMV. By comparison, in
      individual analyses limited to CMV+ participants, less family warmth, less
      harmony, greater dysfunction, and suboptimal parental bonding each were related
      to higher antibody levels, independent of the aforementioned covariates. Findings
      were not attributable to current adult perceptions of psychological stress or
      relative levels of emotional stability. These results suggest that different
      types of childhood adversity may be associated with differential effects on CMV
      infection and latency. 

PMID- 24675034
TI  - Underlying inflammation has no impact on the oxidative stress response to acute
      mental stress.
AB  - INTRODUCTION: Mental stress is considered to be a trigger for acute myocardial
      infarction (MI), with inflammation thought to provide a mechanism. Inflammation
      is reciprocally linked to oxidative stress, which has also been implicated in MI.
      The purpose of this study was to assess the effects of experimentally-induced
      inflammation on the oxidative stress response to mental stress in healthy
      participants. METHODS: Healthy males undertook one of two inflammatory stimuli:
      typhoid vaccination (Vaccination paradigm, N=17) or eccentric exercise (Eccentric
      exercise paradigm, N=17). All participants completed a mental arithmetic stress
      task twice (within-subject design): 6h after the inflammatory stimulus, and
      during a control non-inflammation condition. Blood samples were taken before,
      immediately and 30min after the stress task. Plasma was assessed for interleukin
      6 (IL-6), protein carbonyls (PC), lipid hydroperoxides (LOOH), total antioxidant
      capacity (TAC) and nitric oxide metabolites (NOx). RESULTS: Vaccination paradigm:
      IL-6, PC and NOx were significantly higher in the vaccination condition, relative
      to the control condition (p<.05). PC, TAC, LOOH and NOx were unchanged in
      response to mental stress in both the vaccination and control conditions.
      Eccentric Exercise paradigm: IL-6 and TAC were significantly higher in the
      eccentric exercise condition (p<.05), relative to the control condition. PC, TAC
      and NOx were unchanged in response to mental stress in both the eccentric
      exercise and control conditions. CONCLUSIONS: Two different inflammatory
      paradigms were successful in increasing selective plasma markers of inflammation
      and oxidative stress prior to a mental stress task. However, experimentally
      induced transient inflammation had no impact on mental stress-induced changes in
      plasma LOOH, PC, TAC or NOx in young healthy participants.

PMID- 24675035
TI  - Conformable covered versus uncovered self-expandable metallic stents for
      palliation of malignant gastroduodenal obstruction: a randomized prospective
      study.
AB  - BACKGROUND: A conformable self-expandable metallic stent was developed to
      overcome the limitation of previous self-expandable metallic stents. The aim of
      this study was to evaluate outcomes after placement of conformable covered and
      uncovered self-expandable metallic stents for palliation of malignant
      gastroduodenal obstruction. METHODS: A single-blind, randomized, parallel-group,
      prospective study were conducted in 4 medical centres between March 2009 and July
      2012. 134 patients with unresectable malignant gastroduodenal obstruction were
      assigned to a covered double-layered (n=66) or uncovered unfixed-cell braided
      (n=68) stent placement group. Primary analysis was performed to compare re
      intervention rates between two groups. RESULTS: 120 patients were analysed (59 in
      the covered group and 61 in the uncovered group). Overall rates of re
      intervention were not significantly different between the two groups: 13/59
      (22.0%) in the covered group vs. 13/61 (21.3%) in the uncovered group, p=0.999.
      Stent migration was more frequent in the covered group than in the uncovered
      group (p=0.003). The tumour ingrowth rate was higher in the uncovered group than
      in the covered group (p=0.016). CONCLUSIONS: The rates of re-intervention did not
      significantly differ between the two stents. Conformable covered double-layered
      and uncovered unfixed-cell braided stents were associated with different patterns
      of stent malfunction.

PMID- 24675033
TI  - Innate immune factors modulate ethanol interaction with GABAergic transmission in
      mouse central amygdala.
AB  - Excessive ethanol drinking in rodent models may involve activation of the innate
      immune system, especially toll-like receptor 4 (TLR4) signaling pathways. We used
      intracellular recording of evoked GABAergic inhibitory postsynaptic potentials
      (eIPSPs) in central amygdala (CeA) neurons to examine the role of TLR4 activation
      by lipopolysaccharide (LPS) and deletion of its adapter protein CD14 in acute
      ethanol effects on the GABAergic system. Ethanol (44, 66 or 100mM) and LPS (25
      and 50MUg/ml) both augmented eIPSPs in CeA of wild type (WT) mice. Ethanol (44mM)
      decreased paired-pulse facilitation (PPF), suggesting a presynaptic mechanism of
      action. Acute LPS (25MUg/ml) had no effect on PPF and significantly increased the
      mean miniature IPSC amplitude, indicating a postsynaptic mechanism of action.
      Acute LPS pre-treatment potentiated ethanol (44mM) effects on eIPSPs in WT mice
      and restored ethanol's augmenting effects on the eIPSP amplitude in CD14 knockout
      (CD14 KO) mice. Both the LPS and ethanol (44-66mM) augmentation of eIPSPs was
      diminished significantly in most CeA neurons of CD14 KO mice; however, ethanol at
      the highest concentration tested (100mM) still increased eIPSP amplitudes. By
      contrast, ethanol pre-treatment occluded LPS augmentation of eIPSPs in WT mice
      and had no significant effect in CD14 KO mice. Furthermore, (+)-naloxone, a TLR4
      MD-2 complex inhibitor, blocked LPS effects on eIPSPs in WT mice and delayed the
      ethanol-induced potentiation of GABAergic transmission. In CeA neurons of CD14 KO
      mice, (+)-naloxone alone diminished eIPSPs, and subsequent co-application of
      100mM ethanol restored the eIPSPs to baseline levels. In summary, our results
      indicate that TLR4 and CD14 signaling play an important role in the acute ethanol
      effects on GABAergic transmission in the CeA and support the idea that CD14 and
      TLR4 may be therapeutic targets for treatment of alcohol abuse. 

PMID- 24675036
TI  - Hospital care services for digestive diseases in Italy: the first quantitative
      assessment.
AB  - The scarcity of human and structural resources for specialized gastroenterology
      care is a problem in many Western countries. Data regarding the resources for
      Italian Gastroenterology, so far lacking, have been thus searched and evaluated.
      Based on an agreement protocol between the Italian Association of Hospital
      Gastroenterologists and Endoscopists (AIGO) and the Ministry of Health, national
      data regarding all Institutions providing gastroenterological care were analysed.
      Hospital beds in Gastroenterology units are presented by region, regimen of stay
      and per million inhabitants as of January 2011. Association of Hospital
      Gastroenterologists and Endoscopists also performed a survey of gastroenterology
      units in all Italian regions regarding number of ordinary/day hospital beds and
      the number of staff gastroenterologists. The Ministry data showed a total of 174
      Gastronterology Units in Italy, a total of 2062 hospital beds for the discipline,
      for a proportion of 34.2 beds per million inhabitants. The Association of
      Hospital Gastroenterologists and Endoscopists survey showed a total of 1425
      gastroenterologists in Italy. These data should represent a key reference for
      appropriate planning of specialized care for digestive diseases. 

PMID- 24675037
TI  - One-step endoscopic removal of a giant double esophageal fibrovascular polyp.

PMID- 24675038
TI  - Feasibility of pegylated interferon and ribavirin in hepatitis C-related
      cirrhosis with neutropenia or thrombocytopenia.
AB  - AIM: To investigate the feasibility of pegylated interferon plus ribavirin
      treatment in cirrhotic patients who presented with, or developed while on
      treatment, platelet counts <= 80,000/MUL and/or neutrophil counts <= 1,500/MUL.
      METHODS: A retrospective analysis of prospectively gathered data on 123 cirrhotic
      patients treated with pegylated interferon and ribavirin. Adverse effects and
      haematological changes were monitored: bleeding and infectious events were
      registered and related to platelet and absolute neutrophil counts. RESULTS: Among
      the 58 patients (47.2%) with nadir platelets <= 50,000/MUL during therapy, 6
      (10.3%) experienced a bleeding episode; of the remaining 65 patients with
      platelets constantly >50,000/MUL, 3 (4.6%) bled. Of the 11 bleedings, 3
      manifested during an infection, while patients had platelets >50,000/MUL. Nadir
      neutrophils <= 750/MUL occurred in 45 patients (38.2%) during treatment, and 14
      of them (29.8%) had an infectious event. Infections were also documented in 18 of
      the 76 patients (23.7%) with neutrophils constantly >750/MUL. CONCLUSIONS: The
      study reveals the feasibility of treating cirrhotic patients with cytopenia with
      pegylated interferon and ribavirin, as bleeding or infectious events under
      therapy were unrelated to platelet and neutrophil counts. Withdrawal of therapy
      or variations in the pre-assigned dosages of either pegylated interferon or
      ribavirin owing to abnormally low haematological parameters seems to no longer be
      tenable.

PMID- 24675040
TI  - Composite end points to assess delay of disability progression by MS treatments.
AB  - BACKGROUND: The Expanded Disability Status Scale (EDSS) has low sensitivity and
      reliability for detecting sustained disability progression (SDP) in multiple
      sclerosis (MS) trials. OBJECTIVE: This study evaluated composite disability end
      points as alternatives to EDSS alone. METHODS: SDP rates were determined using 96
      week data from the Olympus trial (rituximab in patients with primary progressive
      MS). SDP was analyzed using composite disability end points: SDP in EDSS, timed
      25-foot walk test (T25FWT), or 9-hole peg test (9HPT) (composite A); SDP in
      T25FWT or 9HPT (composite B); SDP in EDSS and (T25FWT or 9HPT) (composite C); and
      SDP in any two (EDSS, T25FWT, and 9HPT) (composite D). RESULTS: Overall
      agreements between EDSS and other disability measures in defining SDP were 66%
      73%. Composite A showed similar treatment effect estimate versus EDSS alone with
      much higher SDP rates. Composite B, C, and D all showed larger treatment effect
      estimate with different or similar SDP rates versus EDSS alone. Using composite A
      (24-week confirmation only), B, C, or D could reduce sample sizes needed for MS
      trials. CONCLUSION: Composite end points including multiple accepted disability
      measures could be superior to EDSS alone in analyzing disability progression and
      should be considered in future MS trials.

PMID- 24675042
TI  - Speaker-individuality in suprasegmental temporal features: Implications for
      forensic voice comparison.
AB  - Everyday experience tells us that it is often possible to identify a familiar
      speaker solely by his/her voice. Such observations reveal that speakers carry
      individual features in their voices. The present study examines how
      suprasegmental temporal features contribute to speaker-individuality. Based on
      data of a homogeneous group of Zurich German speakers, we conducted an experiment
      that included speaking style variability (spontaneous vs. read speech) and
      channel variability (high-quality vs. mobile phone-transmitted speech), both of
      which are characteristic of forensic casework. Speakers demonstrated high between
      speaker variability in both read and spontaneous speech, and low within-speaker
      variability across the two speaking styles. Results further revealed that
      distortions of the type introduced by mobile telephony had little effect on
      suprasegmental temporal characteristics. Given this evidence of speaker
      individuality, we discuss suprasegmental temporal features' potential for
      forensic voice comparison. 

PMID- 24675041
TI  - The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell
      lung cancer.
AB  - Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK)
      gene rearrangements invariably develop resistance to the ALK tyrosine kinase
      inhibitor (TKI) crizotinib. Herein, we report the first preclinical evaluation of
      the next-generation ALK TKI, ceritinib (LDK378), in the setting of crizotinib
      resistance. An interrogation of in vitro and in vivo models of acquired
      resistance to crizotinib, including cell lines established from biopsies of
      patients with crizotinib-resistant NSCLC, revealed that ceritinib potently
      overcomes crizotinib-resistant mutations. In particular, ceritinib effectively
      inhibits ALK harboring L1196M, G1269A, I1171T, and S1206Y mutations, and a
      cocrystal structure of ceritinib bound to ALK provides structural bases for this
      increased potency. However, we observed that ceritinib did not overcome two
      crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations
      was identified in 5 of 11 biopsies from patients with acquired resistance to
      ceritinib. Altogether, our results demonstrate that ceritinib can overcome
      crizotinib resistance, consistent with clinical data showing marked efficacy of
      ceritinib in patients with crizotinib-resistant disease. SIGNIFICANCE: The second
      generation ALK inhibitor ceritinib can overcome several crizotinib-resistant
      mutations and is potent against several in vitro and in vivo laboratory models of
      acquired resistance to crizotinib. These findings provide the molecular basis for
      the marked clinical activity of ceritinib in patients with ALK-positive NSCLC
      with crizotinib-resistant disease. Cancer Discov; 4(6); 662-73. (c)2014 AACR. See
      related commentary by Ramalingam and Khuri, p. 634 This article is highlighted in
      the In This Issue feature, p. 621.

PMID- 24675043
TI  - Lipid composition of fingermark residue and donor classification using GC/MS.
AB  - Lipids available in fingermark residue represent important targets for
      enhancement and dating techniques. While it is well known that lipid composition
      varies among fingermarks of the same donor (intra-variability) and between
      fingermarks of different donors (inter-variability), the extent of this
      variability remains uncharacterized. Thus, this work aimed at studying
      qualitatively and quantitatively the initial lipid composition of fingermark
      residue of 25 different donors. Among the 104 detected lipids, 43 were reported
      for the first time in the literature. Furthermore, palmitic acid, squalene,
      cholesterol, myristyl myristate and myristyl myristoleate were quantified and
      their correlation within fingermark residue was highlighted. Ten compounds were
      then selected and further studied as potential targets for dating or enhancement
      techniques. It was shown that their relative standard deviation was significantly
      lower for the intra-variability than for the inter-variability. Moreover, the use
      of data pre-treatments could significantly reduce this variability. Based on
      these observations, an objective donor classification model was proposed.
      Hierarchical cluster analysis was conducted on the pre-treated data and the
      fingermarks of the 25 donors were classified into two main groups, corresponding
      to "poor" and "rich" lipid donors. The robustness of this classification was
      tested using fingermark replicates of selected donors. 86% of these replicates
      were correctly classified, showing the potential of such a donor classification
      model for research purposes in order to select representative donors based on
      compounds of interest. 

PMID- 24675044
TI  - Geriatric dyspnea: doing worse, feeling better.
AB  - Older age is associated with a decline in physical fitness and reduced efficiency
      of the respiratory system. Paradoxically, it is also related to reduced report of
      dyspnea, that is, the experience of difficult and uncomfortable breathing.
      Reduced symptom reporting contributes to misdiagnosis or late diagnosis of
      underlying disease, suboptimal treatment, faster disease progression, shorter
      life expectancy, lower quality of life for patients, and considerably increased
      costs for the health care system in an aging society. However, pathways in the
      complex relationship between dyspnea and age are not well explored yet. We
      propose a model on geriatric dyspnea that integrates physiological, neurological,
      psychological and social pathways which link older age with dyspnea perception
      and expression. We suggest that the seemingly paradox of reduction of dyspnea in
      older age, despite physiological decline, can be solved by taking age-related
      changes on these multiple levels into account. In identifying these variables,
      the Geriatric Dyspnea Model highlights risk factors for reduced dyspnea
      perception and report in older age and pathways for intervention. 

PMID- 24675045
TI  - Multivariate models of subjective caregiver burden in dementia: a systematic
      review.
AB  - BACKGROUND: Burden in dementia caregivers is a complex and multidimensional
      construct. Several models of burden and other representations of burden like
      depression or mental health are described in literature. To clarify the state of
      science, we systematically reviewed complex models that include both patient and
      caregiver determinants of caregiver burden. OBJECTIVE: A review of determinant
      models of caregiver burden. DESIGN: Systematic review. DATA SOURCES: Electronic
      databases PubMed, PsycInfo and EMbase were searched in December 2013. STUDY
      SELECTION AND ANALYSIS: Research studies with quantitative outcome measures of
      caregiver burden or burden-related concepts, including both patient and caregiver
      functional characteristics as determinants. We categorized the determinant
      variables in the models and calculated the percentages of proven determinants
      within each category. RESULTS: We found 32 studies with burden models and 24
      depression and mental health models. Patient behavioral problems, caregiver
      coping and personality traits and competence are most consistent determinants of
      caregiver burden, depression and mental health. Behavioral problems are more
      significant than cognitive disorders or lack of self-care. Of all measured
      caregiver personality traits, neuroticism has the strongest impact on caregiver
      burden. Regarding caregiver competences, feeling competent or enjoying higher
      self-efficacy in general diminish caregiver burden and promote caregiver mental
      health.

PMID- 24675046
TI  - Active ingredients against human epidermal aging.
AB  - The decisive role of the epidermis in maintaining body homeostasis prompted
      studies to evaluate the changes in epidermal structure and functionality over the
      lifetime. This development, along with the identification of molecular mechanisms
      of epidermal signaling, maintenance, and differentiation, points to a need for
      new therapeutic alternatives to treat and prevent skin aging. In addition to
      recovering age- and sun-compromised functions, proper treatment of the epidermis
      has important esthetic implications. This study reviews active ingredients
      capable of counteracting symptoms of epidermal aging, organized according to the
      regulation of specific age-affected epidermal functions: (1) several compounds,
      other than retinoids and derivatives, act on the proliferation and
      differentiation of keratinocytes, supporting the protective barrier against
      mechanical and chemical insults; (2) natural lipidic compounds, as well as
      glycerol and urea, are described as agents for maintaining water-ion balance; (3)
      regulation of immunological pathogen defense can be reinforced by natural
      extracts and compounds, such as resveratrol; and (4) antioxidant exogenous
      sources enriched with flavonoids and vitamin C, for example, improve solar
      radiation protection and epidermal antioxidant activity. The main objective is to
      provide a functional classification of active ingredients as regulatory elements
      of epidermal homeostasis, with potential cosmetic and/or dermatological
      applications. 

PMID- 24675047
TI  - Malaria parasites and red cell variants: when a house is not a home.
AB  - PURPOSE OF REVIEW: Multiple red cell variants are known to confer protection from
      malaria. Here, we review advances in identifying new variants that modulate
      malaria risk and in defining molecular mechanisms that mediate malaria
      protection. RECENT FINDINGS: New red cell variants, including an innate variant
      in the red cell's major Ca2+ pump and the acquired state of iron deficiency, have
      been associated with protection from clinical falciparum malaria. The
      polymorphisms hemoglobin C (HbC) and hemoglobin S (HbS) - known to protect
      carriers from severe falciparum malaria - enhance parasite passage to mosquitoes
      and may promote malaria transmission. At the molecular level, substantial
      advances have been made in understanding the impact of HbS and HbC upon the
      interactions between host microRNAs and Plasmodium falciparum protein
      translation; remodeling of red cell cytoskeletal components and transport of
      parasite proteins to the red cell surface; and chronic activation of the human
      innate immune system, which induces tolerance to blood-stage parasites. Several
      polymorphisms have now been associated with protection from clinical vivax
      malaria or reduced Plasmodium vivax density, including Southeast Asian
      ovalocytosis and two common forms of glucose-6-phosphate dehydrogenase
      deficiency. SUMMARY: Red cell variants that modulate malaria risk can serve as
      models to identify clinically relevant mechanisms of pathogenesis, and thus
      define parasite and host targets for next-generation therapies.

PMID- 24675048
TI  - End-of-life decisions in patients with severe acute brain injury.
AB  - Most in-hospital deaths of patients with stroke, traumatic brain injury, or
      postanoxic encephalopathy after cardiac arrest occur after a decision to withhold
      or withdraw life-sustaining treatments. Decisions on treatment restrictions in
      these patients are generally complex and are based only in part on evidence from
      published work. Prognostic models to be used in this decision-making process
      should have a strong discriminative power. However, for most causes of acute
      brain injury, prognostic models are not sufficiently accurate to serve as the
      sole basis of decisions to limit treatment. These decisions are also complicated
      because patients often do not have the capacity to communicate their preferences.
      Additionally, surrogate decision makers might not accurately represent the
      patient's preferences. Finally, in the acute stage, prediction of how a patient
      would adapt to a life with major disability is difficult. 

PMID- 24675049
TI  - In vivo tracking of human neural progenitor cells in the rat brain using
      bioluminescence imaging.
AB  - BACKGROUND: Stem cell therapies appear promising for treating certain
      neurodegenerative disorders and molecular imaging methods that track these cells
      in vivo could answer some key questions regarding their survival and migration.
      Bioluminescence imaging (BLI), which relies on luciferase expression in these
      cells, has been used for this purpose due to its high sensitivity. NEW METHOD: In
      this study, we employ BLI to track luciferase-expressing human neural progenitor
      cells (hNPC(Luc2)) in the rat striatum long-term. RESULTS: We show that
      hNPC(Luc2) are detectable in the rat striatum. Furthermore, we demonstrate that
      using this tracking method, surviving grafts can be detected in vivo for up to 12
      weeks, while those that were rejected do not produce bioluminescence signal. We
      also demonstrate the ability to discern hNPC(Luc2) contralateral migration.
      COMPARISON WITH EXISTING METHODS: Some of the advantages of BLI compared to other
      imaging methods used to track progenitor/stem cells include its sensitivity and
      specificity, low background signal and ability to distinguish surviving grafts
      from rejected ones over the long term while the blood-brain barrier remains
      intact. CONCLUSIONS: These new findings may be useful in future preclinical
      applications developing cell-based treatments for neurodegenerative disorders.

PMID- 24675050
TI  - Constructing fMRI connectivity networks: a whole brain functional parcellation
      method for node definition.
AB  - BACKGROUND: Functional Magnetic Resonance Imaging (fMRI) is used for exploring
      brain functionality, and recently it was applied for mapping the brain connection
      patterns. To give a meaningful neurobiological interpretation to the connectivity
      network, it is fundamental to properly define the network framework. In
      particular, the choice of the network nodes may affect the final connectivity
      results and the consequent interpretation. NEW METHOD: We introduce a novel
      method for the intra subject topological characterization of the nodes of fMRI
      brain networks, based on a whole brain parcellation scheme. The proposed whole
      brain parcellation algorithm divides the brain into clusters that are homogeneous
      from the anatomical and functional point of view, each of which constitutes a
      node. The functional parcellation described is based on the Tononi's cluster
      index, which measures instantaneous correlation in terms of intrinsic and
      extrinsic statistical dependencies. RESULTS: The method performance and
      reliability were first tested on simulated data, then on a real fMRI dataset
      acquired on healthy subjects during visual stimulation. Finally, the proposed
      algorithm was applied to epileptic patients' fMRI data recorded during seizures,
      to verify its usefulness as preparatory step for effective connectivity analysis.
      For each patient, the nodes of the network involved in ictal activity were
      defined according to the proposed parcellation scheme and Granger Causality
      Analysis (GCA) was applied to infer effective connectivity. CONCLUSIONS: We
      showed that the algorithm 1) performed well on simulated data, 2) was able to
      produce reliable inter subjects results and 3) led to a detailed definition of
      the effective connectivity pattern.

PMID- 24675053
TI  - Establishment of bone marrow and hematopoietic niches in vivo by reversion of
      chondrocyte differentiation of human bone marrow stromal cells.
AB  - Human bone marrow stromal cells (BMSCs, also known as bone marrow-derived
      "mesenchymal stem cells") can establish the hematopoietic microenvironment within
      heterotopic ossicles generated by transplantation at non-skeletal sites. Here we
      show that non-mineralized cartilage pellets formed by hBMSCs ex vivo generate
      complete ossicles upon heterotopic transplantation in the absence of exogenous
      scaffolds. These ossicles display a remarkable degree of architectural fidelity,
      showing that an exogenous conductive scaffold is not an absolute requirement for
      bone formation by transplanted BMSCs. Marrow cavities within the ossicles include
      erythroid, myeloid and granulopoietic lineages, clonogenic hematopoietic
      progenitors and phenotypic HSCs, indicating that complete stem cell niches and
      hematopoiesis are established. hBMSCs (CD146(+) adventitial reticular cells) are
      established in the heterotopic chimeric bone marrow through a unique process of
      endochondral bone marrow formation, distinct from physiological endochondral bone
      formation. In this process, chondrocytes remain viable and proliferate within the
      pellet, are released from cartilage, and convert into bone marrow stromal cells.
      Once explanted in secondary culture, these cells retain phenotype and properties
      of skeletal stem cells ("MSCs"), including the ability to form secondary
      cartilage pellets and secondary ossicles upon serial transplantation. Ex vivo,
      hBMSCs initially induced to form cartilage pellets can be reestablished in
      adherent culture and can modulate gene expression between cartilage and stromal
      cell phenotypes. These data show that so-called "cartilage differentiation" of
      BMSCs in vitro is a reversible phenomenon, which is actually reverted, in vivo,
      to the effect of generating stromal cells supporting the homing of hematopoietic
      stem cells and progenitors. 

PMID- 24675054
TI  - (237)Np Mossbauer effect study on NpFeAsO.
AB  - We report (237)Np Mossbauer measurements on NpFeAsO. The Np atoms were found to
      occupy only one crystallographic site. The value of the isomer shift (delta ~ 9.1
      mm s(-1) versus NpAl2) indicates a 5f(4) electronic configuration (Np(3+) ions).
      The magnetic ordering of the Np sublattice below 60 K is established and the
      saturated ordered magnetic moment is determined to be 1.73MUB at 3.6 K. The
      unique set of hyperfine parameters exclude a modulated magnetic structure or spin
      waves on the Np site. The neptunium magnetic moments MUNp are found to lie along
      the tetragonal c-axis. 

PMID- 24675051
TI  - Analytical methods and experimental approaches for electrophysiological studies
      of brain oscillations.
AB  - Brain oscillations are increasingly the subject of electrophysiological studies
      probing their role in the functioning and dysfunction of the human brain. In
      recent years this research area has seen rapid and significant changes in the
      experimental approaches and analysis methods. This article reviews these
      developments and provides a structured overview of experimental approaches,
      spectral analysis techniques and methods to establish relationships between brain
      oscillations and behaviour. 

PMID- 24675055
TI  - Immunohistochemical characterization of the crypt neurons in the olfactory
      epithelium of adult zebrafish.
AB  - The fish sensory epithelium contains three types of sensory cells denominated
      ciliated, microvillous, and crypt neurons. Each one differs from the other in its
      morphological, ultrastructural and molecular features, as well as in their
      projections to the central nervous system. Crypt neurons are present in both bony
      and cartilaginous fish and can be identified on the basis of their morphology and
      the expression of some specific proteins and genes. In this study we have
      investigated the morphology of crypt neurons, as well as the occurrence and co
      localization of S100 protein, calretinin and TRPV4, three proposed markers for
      crypt cells, in the olfactory epithelium of adult zebrafish (Danio rerio) using
      double immunofluorescence associated to laser confocal microscopy. A sparse
      population of superficial S100 protein positive cells was detected being
      identified as crypt neurons. The calretinin immunoreactive cells were more
      abundant, occasionally resembling the morphology of the crypt cells but never
      displaying co-localization of both proteins. The TRPV4 positive cells differed in
      morphology from crypt cells, thus excluding the occurrence of TRPV4 in those
      cells. These results demonstrate that only S100 protein immunoreactivity can be
      used to identify crypt cells. Because some calretinin positive cells showed
      localization and morphology similar to the crypt cells of the sensory epithelium,
      the occurrence of two subtypes of crypt cells, S100 protein and calretinin
      positive, cannot be excluded. The significance of these findings remains to be
      elucidated.

PMID- 24675056
TI  - Self-organized chiral colloidal crystals of Brownian square crosses.
AB  - We study aqueous Brownian dispersions of microscale, hard, monodisperse
      platelets, shaped as achiral square crosses, in two dimensions (2D). When slowly
      concentrated while experiencing thermal excitations, the crosses self-organize
      into fluctuating 2D colloidal crystals. As the particle area fraction phiA is
      raised, an achiral rhombic crystal phase forms at phiA ~ 0.52. Above phiA ~ 0.56,
      the rhombic crystal gives way to a square crystal phase that exhibits long-range
      chiral symmetry breaking (CSB) via a crystal-crystal phase transition; the
      observed chirality in a particular square crystallite has either a positive or a
      negative enantiomeric sense. By contrast to triangles and rhombs, which exhibit
      weak CSB as a result of total entropy maximization, square crosses display robust
      long-range CSB that is primarily dictated by how they tile space at high
      densities. We measure the thermal distribution of orientation angles gamma of the
      crosses' arms relative to the diagonal bisector of the local square crystal
      lattice as a function of phiA, and the average measured gamma (phiA) agrees with
      a re-scaled model involving efficient packing of rotated cross shapes. Our
      findings imply that a variety of hard achiral shapes can be designed to form
      equilibrium chiral phases by considering their tiling at high densities. 

PMID- 24675057
TI  - Point-of-care testing of HbA1C is traceable to IFCC reference method by external
      calibration.
AB  - BACKGROUND: POCT for HbA1C is widely used in China. However, the lack of
      traceability of POCT leads to poor comparability of patient results. METHODS: The
      first step was the evaluation of the precision of NycoCard and DCA by using two
      level patient specimens. The second step was the calibration of the central
      laboratory instrument G8 HBA1C Variant with samples whose values had been
      assigned by an IFCC reference method. The third step was the assignment of values
      to 50 fresh whole blood patient specimens by this calibrated G8. The fourth step
      was to use these 50 fresh whole blood patient specimens to calibrate and to
      revise the POCT instruments. The fifth step was to confirm whether these 50
      specimens were required through mathematical calculations. RESULTS: The low and
      high CVs at levels were 3.61% and 1.85% for NycoCard but 1.71% and 2.85% for DCA.
      The linear equation of NycoCard to calibrated G8 and that of DCA to calibrated G8
      were Y=0.8530X+0.6409 and Y=0.8995X+0.3891, respectively, and the correlation
      coefficient for every POCT instrument was greater than 0.985. By external
      calibration of POCT instruments, the mean deviation detected by NycoCard was
      reduced from -4.0+/-3.4mmol/mol to 0.5+/-3.9mmol/mol, and that by DCA went down
      to 0.2+/-3.3mmol/mol. The minimum specimen size for the external calibration of
      POCT instrument was 10. CONCLUSION: POCT measurement traceability can be
      established by external calibration. Using an external calibration mode improves
      the comparability of POCT patient results.

PMID- 24675058
TI  - Re: Outcomes of combined somatosensory evoked potential, motor evoked potential,
      and electroencephalography monitoring during carotid endarterectomy.

PMID- 24675059
TI  - Regarding 'Combined use of high sensitivity C-reactive protein and N-terminal pro
      B-type natriuretic peptide for risk stratification of vascular surgery patients'.

PMID- 24675060
TI  - Re: "Endovascular repair of a right-sided thoracic aortic aneurysm with Kommerell
      diverticulum and aberrant left subclavian artery".

PMID- 24675062
TI  - Hyperbaric oxygen preconditioning protects rats against CNS oxygen toxicity.
AB  - We examined the hypothesis that repeated exposure to non-convulsive hyperbaric
      oxygen (HBO) as preconditioning provides protection against central nervous
      system oxygen toxicity (CNS-OT). Four groups of rats were used in the study. Rats
      in the control and the negative control (Ctl-) groups were kept in normobaric
      air. Two groups of rats were preconditioned to non-convulsive HBO at 202 kPa for
      1h once every other day for a total of three sessions. Twenty-four hours after
      preconditioning, one of the preconditioned groups and the control rats were
      exposed to convulsive HBO at 608 kPa, and latency to CNS-OT was measured. Ctl-
      rats and the second preconditioned group (PrC-) were not subjected to convulsive
      HBO exposure. Tissues harvested from the hippocampus and frontal cortex were
      evaluated for enzymatic activity and nitrotyrosine levels. In the group exposed
      to convulsive oxygen at 608 kPa, latency to CNS-OT increased from 12.8 to 22.4
      min following preconditioning. A significant decrease in the activity of
      glutathione reductase and glucose-6-phosphate dehydrogenase, and a significant
      increase in glutathione peroxidase activity, was observed in the hippocampus of
      preconditioned rats. Nitrotyrosine levels were significantly lower in the
      preconditioned animals, the highest level being observed in the control rats. In
      the cortex of the preconditioned rats, a significant increase was observed in
      glutathione S-transferase and glutathione peroxidase activity. Repeated exposure
      to non-convulsive HBO provides protection against CNS-OT. The protective
      mechanism involves alterations in the enzymatic activity of the antioxidant
      system and lower levels of peroxynitrite, mainly in the hippocampus.

PMID- 24675061
TI  - Glutamate and GABA imbalance promotes neuronal apoptosis in hippocampus after
      stress.
AB  - BACKGROUND: People who experience traumatic events have an increased risk of post
      traumatic stress disorder (PTSD). However, PTSD-related pathological changes in
      the hippocampus and prefrontal cortex remain poorly understood. MATERIAL AND
      METHODS: We investigated the effect of a PTSD-like animal model induced by severe
      stress. The experimental rats received 20 inescapable electric foot shocks in an
      enclosed box for a total of 6 times in 3 days. The physiological state (body
      weight and plasma corticosterone concentrations), emotion, cognitive behavior,
      brain morphology, apoptosis, and balance of gamma-aminobutyric acid (GABA) and
      glutamate in the hippocampus and prefrontal cortex were observed. Cell damages
      were examined with histological staining (HE, Nissl, and silver impregnation),
      while apoptosis was analyzed with flow cytometry using an Annexin V and propidium
      iodide (PI) binding and terminal deoxynucleotidyl transferase mediated-dUTP nick
      end labeling (TUNEL) method. RESULTS: In comparison with the sham litter-mates,
      the stressed rats showed decreased body weight, inhibition of hypothalamic
      pituitary-adrenal (HPA) axis activation, increase in freezing response to trauma
      reminder, hypoactivity and anxiety-like behaviors in elevated plus maze and open
      field test, poor learning in Morris water maze, and shortened latency in hot
      plate test. There were significant damages in the hippocampus but not in the
      prefrontal cortex. Imbalance between glutamate and GABA was more evident in the
      hippocampus than in the prefrontal cortex. CONCLUSIONS: These results suggest
      that neuronal apoptosis in the hippocampus after severe traumatic stress is
      related to the imbalance between glutamate and GABA. Such modifications may
      resemble the profound changes observed in PTSD patients.

PMID- 24675063
TI  - Alcohol-related sickness absence among young employees: gender differences and
      the prevention paradox.
AB  - BACKGROUND: Few studies have examined alcohol-related sickness absence among
      young employees, although young adults are known to drink quite heavily. There
      are substantial differences in drinking patterns between men and women, yet
      gender differences have rarely been the main focus in research on alcohol-related
      sickness absence. Thus the present paper aims to examine gender differences in
      the prevalence of alcohol-related sickness absence among young employees in
      Norway, and in the associations between drinking patterns and such absence.
      Further, to examine whether the prevention paradox applies to alcohol-related
      sickness absence among both genders. METHODS: A sample of employed young adults,
      49.7% male (N = 1762, mean age = 28.3; SD = 1.9), was obtained from a general
      population survey of Norwegians. Self-reported measures on alcohol-related
      sickness absence and various drinking measures were applied. RESULTS: Men
      reported absence from work due to drinking almost twice as often as women. There
      was a statistically significant gender difference in the drinking-absence
      association only for one of the three alcohol measures, indicating a stronger
      relationship among women. The heaviest drinkers (about 6% of the sample) reported
      a disproportionally large share of alcohol-related sickness absence (19%), yet
      the vast majority of such absence was found among the moderate drinkers (81%).
      CONCLUSIONS: Alcohol-related sickness absence is more common among men than
      women. This gender difference may reflect differences in drinking habits rather
      than the likelihood of being absent after drinking. The results indicate that the
      prevention paradox applies to alcohol-related sickness absence among young
      employees of both genders.

PMID- 24675064
TI  - Development of loop-mediated isothermal amplification and SYBR green real-time
      PCR methods for the detection of Citrus yellow mosaic badnavirus in citrus
      species.
AB  - Citrus yellow mosaic badnavirus (CMBV) is an important pathogen in southern India
      spread by infected citrus propagules. One of the measures to arrest the spread of
      CMBV is to develop methods to screen and certify citrus propagules as CMBV-free.
      The methods loop-mediated isothermal amplification (LAMP) and SYBR green real
      time PCR (SGRTPCR) have been developed for the efficient detection of CMBV in
      citrus propagules. This paper compares the sensitivities of LAMP and SGRTPCR with
      polymerase chain reaction (PCR) for the detection of CMBV. Whereas PCR and LAMP
      were able to detect CMBV from a minimum of 10 ng of total DNA of infected leaf
      samples, SGRTPCR could detect the same from 1 ng of total DNA. Using SGRTPCR, the
      viral titres were estimated to be the highest in rough lemon and lowest in Nagpur
      Mandarin of the five naturally infected citrus species tested. The results will
      help in designing suitable strategies for the sensitive detection of CMBV from
      citrus propagules.

PMID- 24675065
TI  - Characterization of bla(OxA-23) gene regions in isolates of Acinetobacter
      baumannii.
AB  - BACKGROUND/PURPOSE: To investigate the characterization of bla(OxA-23) gene
      regions in isolates of Acinetobacter baumannii from Taizhou Municipal Hospital.
      METHODS: Fifty-nine non-repetitive, multiresistant (including imipenem-resistant)
      isolates of A. baumannii were recovered from clinical infections in hospitalized
      patients from January 2010 to August 2011 in Taizhou Municipal Hospital
      (affiliated with Taizhou University) in China. These isolates were genotyped
      using pulsed-field gel electrophoresis (PFGE). bla(OxA-23) beta-lactamase and
      associated genetic structures were analyzed using polymerase chain reaction
      (PCR), and recombination plasmids were analyzed by BamHI- or SacI- restriction
      enzyme digestion; predicted promoter structures of bla(OxA-23) genes were
      determined and compared using protein-protein BLAST analysis. RESULTS: Fifteen
      out of 59 isolates expressing imipenem-resistant A. baumannii clinical isolates
      acquired either a bla(OxA-23) beta-lactamase gene. A new gene cluster (ISAba1
      bla(OxA-23)-AMP) with three previously identified transposons (Tn2006, Tn2007,
      and Tn2008) and one previously identified gene cluster (ISAba1- bla(OxA-23)) was
      found in the isolates. Recombination plasmids were analyzed by restriction enzyme
      digestion. CONCLUSION: Our results indicate that pattern A was the most prevalent
      molecular type based on PFGE, and that different clones might be widespread with
      a majority of ISAba1-bla(OxA-23) clonal lineages in the 15 PCR positive isolates
      of A. baumannii in the hospital.

PMID- 24675066
TI  - Neurofibromatosis type 2 vestibular schwannoma treatment: a review of the
      literature, trends, and outcomes.
AB  - OBJECTIVE: Review the useful hearing preservation and tumor control outcomes of
      microsurgery (MS), stereotactic radiation (SR), conservative management (CM), and
      chemotherapy (ChT) for Neurofibromatosis type 2 vestibular schwannomas. DATA
      SOURCES: Ovid MEDLINE was used to conduct a thorough search of English-language
      publications dating from 1948 to February 2013. STUDY SELECTION: Patients must
      have had useful hearing at diagnosis and treated with one of the 4 treatments as
      their primary therapy. All sporadic vestibular schwannoma cases were excluded.
      DATA EXTRACTION: A total of 19 articles were reviewed. Hearing preservation was
      defined as unchanged or improved useful hearing. Tumor control was defined as no
      change in size or tumor regression for SR, CM, and ChT-treated cases, and as no
      recurrence for MS treated cases. CONCLUSION: Microsurgery seems to have the worse
      overall results, while SR has very good tumor control with poor useful hearing
      preservation. If a patient qualifies for CM, he is likely to show the most
      satisfactory results with the least treatment available. A close follow-up on ChT
      clinical trials and possible side-effects is warranted as preliminary short-term
      results are quite favorable. Additional long-term studies are required for a
      better understanding of this disease.

PMID- 24675067
TI  - Response to: safe levels of acoustic stimulation: comment on "effects of acoustic
      stimuli used for vestibular evoked potential studies on the cochlear function".

PMID- 24675068
TI  - Immunogen design to focus the B-cell repertoire.
AB  - PURPOSE OF REVIEW: This review aims to bring together recent developments
      relevant to the design of HIV-1 envelope glycoprotein-based immunogens to elicit
      broadly neutralizing antibodies (bNAbs). RECENT FINDINGS: The combined use of
      structural biology and deep sequencing of antigen-specific B-cell lineages has
      allowed cross-sectional and longitudinal views of antibody evolution towards
      broad and potent neutralization of HIV-1. Recent advances in molecular modelling
      allied with protein and glycoprotein engineering have fuelled the design of new
      generation viral envelope glycoproteins (Env)-based antigens. SUMMARY: Although
      proof-of-principle for vaccine elicitation of bNAbs to HIV-1 is still lacking,
      many of the conceptual hurdles are being addressed.

PMID- 24675069
TI  - Phagocytosis: cell biology view of antiviral function.
AB  - PURPOSE OF REVIEW: Recently, studies have suggested a role for Fc-mediated
      effector functions in viremic control of HIV infection and blocking HIV
      acquisition. Although progress has been made in identifying the mechanisms
      responsible for regulating various innate functions, minimal research has been
      performed concerning macrophage-specific phagocytosis and antiviral effects.
      RECENT FINDINGS: Of what research has been performed, phagocytosis has been
      identified as a possible key player in antiviral functions during initial
      infection, offering protection at the HIV mucosal entry sites. Recent research
      has also highlighted the importance of various antibody characteristics, such as
      polymorphism, immunoglobulin subclass, and glycan structure on those effector
      functions modulated. Lastly, despite recent failures in HIV vaccine trials, the
      RV144 Thai trial illustrated 31.2% efficacy against heterosexual infection. When
      these protective results were looked at in depth, vaccine-induced antibodies were
      increased when infection rates decreased, suggesting that HIV might be
      neutralized through receptor-mediated effector mechanisms, including
      phagocytosis. Importantly, these data instilled the awareness that the
      identification of protective immune correlates is imperative to successfully
      develop vaccine strategies. SUMMARY: In this review, we address the antiviral
      mechanisms of phagocytosis, focusing on complement-mediated phagocytosis and Fc
      receptor-mediated antibody-dependent cellular phagocytosis in relation to HIV
      transmission and infection.

PMID- 24675070
TI  - Determining common insertion sites based on retroviral insertion distribution
      across tumors.
AB  - A CIS (common insertion site) indicates a genome region that is hit more
      frequently by retroviral insertions than expected by chance. Such a region is
      strongly related to cancer gene loci, which leads to the detection of cancer
      genes. An algorithm for detecting CISs should satisfy the following: (1) it does
      not require any prior knowledge of underlying insertion distribution; (2) it can
      resolve the insertion biases caused by hotspots; (3) it can detect CISs of any
      biological width; (4) it can identify noises resulting from statistic mistakes
      and non-CIS insertions; and (5) it can identify the widths of CISs as accurately
      as possible. We develop a method to resolve these difficulties. We verify a
      region's significance from two perspectives: distribution width and distribution
      depth. The former indicates how many insertions in a region while the latter
      evaluates the insertion distribution across the tumors in a region. We compare
      our method with kernel density estimation and sliding window on the simulated
      data, showing that our method not only identifies cancer-related insertions
      effectively, but also filters noises correctly. The experiments on the real data
      show that taking insertion distribution into account can highlight significant
      CISs. We detect 53 novel CISs, some of which have been proven correct by the
      biological literature. 

PMID- 24675071
TI  - Development of a comprehensive near infrared spectroscopy calibration model for
      rapid measurements of moisture content in multiple pharmaceutical products.
AB  - Near infrared (NIR) spectroscopy has been widely used for the determination of
      water content in a wide variety of samples. With few exceptions, all methods
      employ a calibration model developed and applicable for a single product. The
      current study describes a NIR method using a single, comprehensive calibration
      model to predict the water content in tablets containing different active
      pharmaceutical ingredients (API). The calibration model was developed for water
      content range of 2-13% (w/w) using tablets containing three different APIs and
      different formulation compositions. To develop a robust comprehensive model,
      individual calibration models were sequentially developed starting from a simple
      model for one product to including tablets from all three projects in the final
      model using partial least square analysis method. Data pretreatments and spectral
      region selections were performed during the method development to optimize the
      number of factors and the correlation coefficients for cross-validation and
      prediction by the comprehensive model. The model reliably predicted the water
      content in tablet samples of these three products, and can be updated for water
      measurements of new drug products by adding to the model two samples of the new
      product for calibration purpose. 

PMID- 24675072
TI  - Post-column mobile phase adjustment: a strategy to eliminate the contradiction
      between liquid chromatography and mass spectrometry in the determination of
      flavonoids in rat plasma.
AB  - Flavonoids are a group of important naturally occurring polyphenolic compounds
      with a wide range of biological effects. In this study, a sensitive liquid
      chromatography tandem mass spectrometry method was developed to simultaneously
      determine multiple active flavonoids, including quercetin (Que), kaempferol
      (Kae), apigenin (Api), isorhamnetin (Iso), luteolin (Lut), and naringenin (Nar),
      in rat plasma. To achieve a satisfied peak shape and LC separation, formic acid
      with the concentration between 0.05 and 0.2%, or in some case 5%, was generally
      used to acidify the LC mobile phase in reported studies. Here we found that even
      0.05% formic acid could lead to strong mass signal suppression, and the absence
      of formic acid could reverse the signal suppression but cause serious peak
      tailing. There is an irreconcilable contradiction between liquid chromatography
      (LC) and mass spectrometry (MS). In order to simultaneously satisfy LC and MS, LC
      mobile phase with 0.00075% formic acid and post column mobile phase adjustment
      with 0.0677% ammonium solution in isopropanol were applied. Compared with the
      conventional method with mobile phase containing 0.05% formic acid, the mass
      signal response of Que, Kae, Api, Iso, Lut, Nar, and Oka increased 26.2, 18.6,
      13.6, 23.5, 17.5, 15.6 and 15.4 fold, respectively. In addition, the post column
      mobile phase addition exhibited the better peak shape for the reduction of
      analytes longitudinal diffusion. The method has been fully validated according to
      FDA guidelines within the linear range between 0.328 ng mL-1 and 168 ng mL-1, and
      successfully applied to a pilot pharmacokinetic study of rats after administering
      5.43 g kg-1 Pollen of Brassica campestris.

PMID- 24675073
TI  - The species- and site-specific acid-base properties of biological thiols and
      their homodisulfides.
AB  - Cysteamine, cysteine, homocysteine, their homodisulfides and 9 related compounds
      were studied by 1H NMR-pH titrations and case-tailored evaluation methods. The
      resulting acid-base properties are quantified in terms of 33 macroscopic and 62
      microscopic protonation constants and the concomitant 16 interactivity
      parameters, providing thus the first complete microspeciation of this vitally
      important family of biomolecules. The species- and site-specific basicities are
      interpreted by means of inductive and hydrogen-bonding effects through various
      intra- and intermolecular comparisons. The pH-dependent distribution of the
      microspecies is depicted. The thiolate basicities determined this way provide
      exclusive means for the prediction of thiolate oxidizabilities, a key parameter
      to understand and influence oxidative stress at the molecular level.

PMID- 24675074
TI  - Vinculin regulates osteoclast function.
AB  - Osteoclastic bone resorption depends upon the cell's ability to organize its
      cytoskeleton. Because vinculin (VCL) is an actin-binding protein, we asked
      whether it participates in skeletal degradation. Thus, we mated VCL(fl/fl) mice
      with those expressing cathepsin K-Cre (CtsK-VCL) to delete the gene in mature
      osteoclasts or lysozyme M-Cre (LysM-VCL) to target all osteoclast lineage cells.
      VCL-deficient osteoclasts differentiate normally but, reflecting cytoskeletal
      disorganization, form small actin rings and fail to effectively resorb bone. In
      keeping with inhibited resorptive function, CtsK-VCL and LysM-VCL mice exhibit a
      doubling of bone mass. Despite cytoskeletal disorganization, the capacity of VCL(
      /-) osteoclastic cells to normally phosphorylate c-Src in response to alphavbeta3
      integrin ligand is intact. Thus, integrin-activated signals are unrelated to the
      means by which VCL organizes the osteoclast cytoskeleton. WT VCL completely
      rescues actin ring formation and bone resorption, as does VCL(P878A), which is
      incapable of interacting with Arp2/3. As expected, deletion of the VCL tail
      domain (VCL(1-880)), which binds actin, does not normalize VCL(-/-) osteoclasts.
      The same is true regarding VCL(I997A), which also prevents VCL/actin binding, and
      VCL(A50I) and VCL(811-1066), both of which arrest talin association. Thus, VCL
      binding talin, but not Arp2/3, is critical for osteoclast function, and its
      selective inhibition retards physiological bone loss. 

PMID- 24675075
TI  - SRA gene knockout protects against diet-induced obesity and improves glucose
      tolerance.
AB  - We have recently shown that the non-coding RNA, steroid receptor RNA activator
      (SRA), functions as a transcriptional coactivator of PPARgamma and promotes
      adipocyte differentiation in vitro. To assess SRA function in vivo, we have
      generated a whole mouse Sra1 gene knock-out (SRA(-/-)). Here, we show that the
      Sra1 gene is an important regulator of adipose tissue mass and function. SRA is
      expressed at a higher level in adipose tissue than other organs in wild type
      mice. SRA(-/-) mice are resistant to high fat diet-induced obesity, with
      decreased fat mass and increased lean content. This lean phenotype of SRA(-/-)
      mice is associated with decreased expression of a subset of adipocyte marker
      genes and reduced plasma TNFalpha levels. The SRA(-/-) mice are more insulin
      sensitive, as evidenced by reduced fasting insulin, and lower blood glucoses in
      response to IP glucose and insulin. In addition, the livers of SRA(-/-) mice have
      fewer lipid droplets after high fat diet feeding, and the expression of
      lipogenesis-associated genes is decreased. To our knowledge, these data are the
      first to indicate a functional role for SRA in adipose tissue biology and glucose
      homeostasis in vivo. 

PMID- 24675076
TI  - Mitochondrial metabolism of pyruvate is essential for regulating glucose
      stimulated insulin secretion.
AB  - It is well known that mitochondrial metabolism of pyruvate is critical for
      insulin secretion; however, we know little about how pyruvate is transported into
      mitochondria in beta-cells. Part of the reason for this lack of knowledge is that
      the carrier gene was only discovered in 2012. In the current study, we assess the
      role of the recently identified carrier in the regulation of insulin secretion.
      Our studies show that beta-cells express both mitochondrial pyruvate carriers
      (Mpc1 and Mpc2). Using both pharmacological inhibitors and siRNA-mediated
      knockdown of the MPCs we show that this carrier plays a key role in regulating
      insulin secretion in clonal 832/13 beta-cells as well as rat and human islets. We
      also show that the MPC is an essential regulator of both the ATP-regulated
      potassium (KATP) channel-dependent and -independent pathways of insulin
      secretion. Inhibition of the MPC blocks the glucose-stimulated increase in two
      key signaling molecules involved in regulating insulin secretion, the ATP/ADP
      ratio and NADPH/NADP(+) ratio. The MPC also plays a role in in vivo glucose
      homeostasis as inhibition of MPC by the pharmacological inhibitor alpha-cyano
      beta-(1-phenylindol-3-yl)-acrylate (UK5099) resulted in impaired glucose
      tolerance. These studies clearly show that the newly identified mitochondrial
      pyruvate carrier sits at an important branching point in nutrient metabolism and
      that it is an essential regulator of insulin secretion. 

PMID- 24675077
TI  - The role of the human psoralen 4 (hPso4) protein complex in replication stress
      and homologous recombination.
AB  - Psoralen 4 (Pso4) is an evolutionarily conserved protein that has been implicated
      in a variety of cellular processes including RNA splicing and resistance to
      agents that cause DNA interstrand cross-links. Here we show that the hPso4
      complex is required for timely progression through S phase and transition through
      the G2/M checkpoint, and it functions in the repair of DNA lesions that arise
      during replication. Notably, hPso4 depletion results in delayed resumption of DNA
      replication after hydroxyurea-induced stalling of replication forks, reduced
      repair of spontaneous and hydroxyurea-induced DNA double strand breaks (DSBs),
      and increased sensitivity to a poly(ADP-ribose) polymerase inhibitor.
      Furthermore, we show that hPso4 is involved in the repair of DSBs by homologous
      recombination, probably by regulating the BRCA1 protein levels and the generation
      of single strand DNA at DSBs. Together, our results demonstrate that hPso4
      participates in cell proliferation and the maintenance of genome stability by
      regulating homologous recombination. The involvement of hPso4 in the
      recombinational repair of DSBs provides an explanation for the sensitivity of
      Pso4-deficient cells to DNA interstrand cross-links. 

PMID- 24675079
TI  - Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain
      swapping.
AB  - Periaxin (PRX) is an abundant protein in the peripheral nervous system, with an
      important role in myelination. PRX participates in large molecular complexes,
      most likely through the interactions of its N-terminal PSD-95/Discs-large/ZO-1
      (PDZ)-like domain. We present the crystal structures of the PDZ-like domains from
      PRX and its homologue AHNAK nucleoprotein 2 (AHNAK2). The unique intertwined,
      domain-swapped dimers provide a structural basis for the homodimerization of both
      proteins. The core of the homodimer is formed by a 6-stranded antiparallel beta
      sheet, with every other strand from a different chain. The AHNAK2 PDZ domain
      structure contains a bound class III ligand peptide. The binding pocket is
      preformed, and the peptide-PDZ interactions have unique aspects, including two
      salt bridges and weak recognition of the peptide C terminus. Tight
      homodimerization may be central to the scaffolding functions of PRX and AHNAK2 in
      molecular complexes linking the extracellular matrix to the cytoskeletal network.

PMID- 24675078
TI  - Increased glucose metabolism and glycerolipid formation by fatty acids and GPR40
      receptor signaling underlies the fatty acid potentiation of insulin secretion.
AB  - Acute fatty acid (FA) exposure potentiates glucose-stimulated insulin secretion
      in beta cells through metabolic and receptor-mediated effects. We assessed the
      effect of fatty acids on the dynamics of the metabolome in INS-1 cells following
      exposure to [U-(13)C]glucose to assess flux through metabolic pathways.
      Metabolite profiling showed a fatty acid-induced increase in long chain acyl-CoAs
      that were rapidly esterified with glucose-derived glycerol-3-phosphate to form
      lysophosphatidic acid, mono- and diacylglycerols, and other glycerolipids, some
      implicated in augmenting insulin secretion. Glucose utilization and glycolytic
      flux increased, along with a reduction in the NADH/NAD(+) ratio, presumably by an
      increase in conversion of dihydroxyacetone phosphate to glycerol-3-phosphate. The
      fatty acid-induced increase in glycolysis also resulted in increases in
      tricarboxylic cycle flux and oxygen consumption. Inhibition of fatty acid
      activation of FFAR1/GPR40 by an antagonist decreased glycerolipid formation,
      attenuated fatty acid increases in glucose oxidation, and increased mitochondrial
      FA flux, as evidenced by increased acylcarnitine levels. Conversely, FFAR1/GPR40
      activation in the presence of low FA increased flux into glycerolipids and
      enhanced glucose oxidation. These results suggest that, by remodeling glucose and
      lipid metabolism, fatty acid significantly increases the formation of both lipid-
      and TCA cycle-derived intermediates that augment insulin secretion, increasing
      our understanding of mechanisms underlying beta cell insulin secretion. 

PMID- 24675080
TI  - The inner membrane complex sub-compartment proteins critical for replication of
      the apicomplexan parasite Toxoplasma gondii adopt a pleckstrin homology fold.
AB  - Toxoplasma gondii, an apicomplexan parasite prevalent in developed nations,
      infects up to one-third of the human population. The success of this parasite
      depends on several unique structures including an inner membrane complex (IMC)
      that lines the interior of the plasma membrane and contains proteins important
      for gliding motility and replication. Of these proteins, the IMC sub-compartment
      proteins (ISPs) have recently been shown to play a role in asexual T. gondii
      daughter cell formation, yet the mechanism is unknown. Complicating mechanistic
      characterization of the ISPs is a lack of sequence identity with proteins of
      known structure or function. In support of elucidating the function of ISPs, we
      first determined the crystal structures of representative members TgISP1 and
      TgISP3 to a resolution of 2.10 and 2.32 A, respectively. Structural analysis
      revealed that both ISPs adopt a pleckstrin homology fold often associated with
      phospholipid binding or protein-protein interactions. Substitution of basic for
      hydrophobic residues in the region that overlays with phospholipid binding in
      related pleckstrin homology domains, however, suggests that ISPs do not retain
      phospholipid binding activity. Consistent with this observation, biochemical
      assays revealed no phospholipid binding activity. Interestingly, mapping of
      conserved surface residues combined with crystal packing analysis indicates that
      TgISPs have functionally repurposed the phospholipid-binding site likely to
      coordinate protein partners. Recruitment of larger protein complexes may also be
      aided through avidity-enhanced interactions resulting from multimerization of the
      ISPs. Overall, we propose a model where TgISPs recruit protein partners to the
      IMC to ensure correct progression of daughter cell formation. 

PMID- 24675081
TI  - MicroRNA-9 and microRNA-326 regulate human dopamine D2 receptor expression, and
      the microRNA-mediated expression regulation is altered by a genetic variant.
AB  - The human dopamine receptor D2 (DRD2) has been implicated in the pathophysiology
      of schizophrenia and other neuropsychiatric disorders. Most antipsychotic drugs
      influence dopaminergic transmission through blocking dopamine receptors,
      primarily DRD2. We report here the post-transcriptional regulation of DRD2
      expression by two brain-expressed microRNAs (miRs), miR-326 and miR-9, in an ex
      vivo mode, and show the relevance of miR-mediated DRD2 expression regulation in
      human dopaminergic neurons and in developing human brains. Both miRs targeted the
      3'-UTR (untranslated region) of DRD2 in NT2 (neuron-committed teratocarcinoma,
      which endogenously expresses DRD2) and CHO (Chinese hamster ovary) cell lines,
      decreasing luciferase activity measured by a luciferase reporter gene assay. miR
      326 overexpression reduced DRD2 mRNA and DRD2 receptor synthesis. Both antisense
      miR-326 and antisense miR-9 increased DRD2 protein abundance, suggesting an
      endogenous repression of DRD2 expression by both miRs. Furthermore, a genetic
      variant (rs1130354) within the DRD2 3'-UTR miR-targeting site interferes with miR
      326-mediated repression of DRD2 expression. Finally, co-expression analysis
      identified an inverse correlation of DRD2 expression with both miR-326 and miR-9
      in differentiating dopaminergic neurons derived from human induced pluripotent
      stem cells (iPSCs) and in developing human brain regions implicated in
      schizophrenia. Our study provides empirical evidence suggesting that miR-326 and
      miR-9 may regulate dopaminergic signaling, and miR-326 and miR-9 may be
      considered as potential drug targets for the treatment of disorders involving
      abnormal DRD2 function, such as schizophrenia. 

PMID- 24675083
TI  - Dramatic resolution of bullous pemphigoid after surgery for gastric cancer: A
      case report.
AB  - INTRODUCTION: An association between bullous pemphigoid (BP) and internal
      malignancy has been suggested. However, no reports have documented a dramatic
      improvement in BP after surgery for gastric cancer. PRESENTATION OF CASE: An 82
      year-old Japanese woman was admitted to a local hospital for severe fatigue. On
      examination, she was diagnosed with BP and gastric cancer. Her BP was resistant
      to steroid treatment; however, it improved dramatically after surgery for gastric
      cancer. DISCUSSION: In this case, a strong relationship appeared to exist between
      BP and gastric cancer. CONCLUSION: This is the first report of a dramatic
      improvement in BP after surgery for gastric cancer.

PMID- 24675082
TI  - Alternative splicing governs cone cyclic nucleotide-gated (CNG) channel
      sensitivity to regulation by phosphoinositides.
AB  - Precursor mRNA encoding CNGA3 subunits of cone photoreceptor cyclic nucleotide
      gated (CNG) channels undergoes alternative splicing, generating isoforms
      differing in the N-terminal cytoplasmic region of the protein. In humans, four
      variants arise from alternative splicing, but the functional significance of
      these changes has been a persistent mystery. Heterologous expression of the four
      possible CNGA3 isoforms alone or with CNGB3 subunits did not reveal significant
      differences in basic channel properties. However, inclusion of optional exon 3,
      with or without optional exon 5, produced heteromeric CNGA3 + CNGB3 channels
      exhibiting an ~2-fold greater shift in K1/2,cGMP after phosphatidylinositol 4,5
      biphosphate or phosphatidylinositol 3,4,5-trisphosphate application compared with
      channels lacking the sequence encoded by exon 3. We have previously identified
      two structural features within CNGA3 that support phosphoinositides (PIPn)
      regulation of cone CNG channels: N- and C-terminal regulatory modules. Specific
      mutations within these regions eliminated PIPn sensitivity of CNGA3 + CNGB3
      channels. The exon 3 variant enhanced the component of PIPn regulation that
      depends on the C-terminal region rather than the nearby N-terminal region,
      consistent with an allosteric effect on PIPn sensitivity because of altered N-C
      coupling. Alternative splicing of CNGA3 occurs in multiple species, although the
      exact variants are not conserved across CNGA3 orthologs. Optional exon 3 appears
      to be unique to humans, even compared with other primates. In parallel, we found
      that a specific splice variant of canine CNGA3 removes a region of the protein
      that is necessary for high sensitivity to PIPn. CNGA3 alternative splicing may
      have evolved, in part, to tune the interactions between cone CNG channels and
      membrane-bound phosphoinositides. 

PMID- 24675085
TI  - Expression, purification and functional characterization of AmiA of acetamidase
      operon of Mycobacterium smegmatis.
AB  - Regulation of gene expression is one of the mechanisms of virulence in pathogenic
      organisms. In this context, we would like to understand the gene regulation of
      acetamidase enzyme of Mycobacterium smegmatis, which is the first reported
      inducible enzyme in mycobacteria. The acetamidase is highly inducible and the
      expression of this enzyme is increased 100-fold when the substrate acetamide is
      added. The acetamidase structural gene (amiE) is found immediately downstream of
      three predicted open reading frames (ORFs). Three of these genes along with a
      divergently expressed ORF are predicted to form an operon and involved in the
      regulation of acetamidase enzyme. Here we report expression, purification and
      functional characterization of AmiA which is one of these predicted ORFs.
      Electrophoretic mobility shift assays showed that AmiA binds to the region
      between the amiA and amiD near the predicted promoter (P2). Over-expression of
      AmiA significantly lowered the expression of acetamidase compared to the wild
      type as demonstrated by qRT-PCR and SDS-PAGE. We conclude that AmiA binds near P2
      promoter and acts as a repressor in the regulation of acetamidase operon. The
      described work is a further step forward toward broadening the knowledge on
      understanding of the complex gene regulatory mechanism of Mycobacterium sp. 

PMID- 24675084
TI  - Adiponectin/T-cadherin and apelin/APJ expression in human arteries and
      periadventitial fat: implication of local adipokine signaling in atherosclerosis?
AB  - INTRODUCTION: Adipose tissue is considered an endocrine organ, producing
      bioactive peptides, called adipokines. Adipokines produced by periadventitial fat
      have been implicated in the pathogenesis of vascular disease, including
      atherosclerosis. Adiponectin has established antiatherogenic actions, while the
      role of T-cadherin as an adiponectin receptor is not fully elucidated. The
      apelinergic system, consisting of apelin and its APJ receptor, is a mediator of
      various cardiovascular functions and may also be involved in the atherosclerotic
      process. We investigated the protein expression of adiponectin, T-cadherin,
      apelin and APJ in human aortas, coronary vessels, and the respective
      periadventitial adipose tissue and correlated their expression with the presence
      of atherosclerosis and clinical parameters. METHODS: Immunohistochemistry for
      adiponectin, T-cadherin, apelin, and APJ was performed on human aortic and
      coronary artery samples including the periadventitial adipose tissue. Aortic and
      coronary atherosclerotic lesions were assessed using the american heart
      association (AHA) classification. RESULTS: Adiponectin immunostaining, of varied
      intensity, was detected only in adipocytes, while T-cadherin was localized to
      vascular smooth muscle cells (VSMCs) and endothelial cells. Apelin immunostaining
      was detected in adipocytes, VSMCs, endothelial cells, and foam cells in
      atherosclerotic lesions, while APJ was found in VSMCs and endothelia.
      Periadventitial adiponectin and VSMC T-cadherin expression were negatively
      correlated with atherosclerosis in both sites, as was VSMC apelin expression.
      Several other - depot specific - associations were observed. CONCLUSIONS: Our
      results suggest a possible role for T-cadherin as a mediator of antiatherogenic
      adiponectin actions, while they support the putative antiatherogenic profile for
      apelin and its APJ receptor in human arteries. Further research is absolutely
      necessary to confirm these notions. SUMMARY: Periadventitial adipose tissue
      adipokines are implicated in vascular physiology and pathology. Adiponectin/T
      cadherin and apelin/APJ immunoreactivity is detected in human aortas and coronary
      arteries. Adiponectin/T-cadherin and apelin/APJ expression patterns were found to
      be inversely associated with human aortic and coronary atherosclerosis.

PMID- 24675086
TI  - Chromosome breakage induced by the genotoxic agents mitomycin C and cytosine
      arabinoside is concentration and p53 dependent.
AB  - The p53 tumor suppressor protein plays an essential role in cellular integrity
      and inactivation of the TP53 gene by mutation is the most frequent alteration in
      human cancer. As loss of p53 function is associated with increased genetic
      instability, it is important in genotoxicity testing to explore the role of p53
      competency. In vitro model systems for genotoxicity testing are sometimes prone
      to misleading positive results; some of this loss of predictivity may be caused
      by p53 inactivation in some cell models. To explore whether impaired p53 function
      plays a role in mutation sensitivity, TK6 cells (p53 competent) and NH32 cells
      (p53 deficient) were treated with two known genotoxicants, mitomycin C (MMC) and
      cytosine arabinoside (araC). Chromosomal damage was assessed in the low dose
      region by an automated micronucleus system and p53 activity was investigated by
      gene and protein expression analysis. Cell cycle progression studies were also
      assessed. Low levels of micronucleus and p53 induction were observed in TK6 cells
      treated with MMC. On the other hand, higher levels of micronucleus and p53
      induction were shown in TK6 cells treated with araC and a G1/S arrest was
      observed after araC treatment. p53 deficient NH32 cells showed an increased
      sensitivity of micronucleus (MN) induction after araC treatment compared with TK6
      cells and less of an active G1/S phase checkpoint. Thus, impaired p53 function
      sensitizes cells to genotoxicants and plays a central role in the DNA damage
      response. This data has clear importance for safety assessment of genotoxicity
      and shows how crucial p53 competence is. 

PMID- 24675087
TI  - Genomic allergen rapid detection in-house validation--a proof of concept.
AB  - Chemical sensitization is an adverse immunologic response to chemical substances,
      inducing hypersensitivity in exposed individuals. Identifying chemical
      sensitizers is of great importance for chemical, pharmaceutical, and cosmetic
      industries, in order to prevent the use of sensitizers in consumer products.
      Historically, chemical sensitizers have been assessed mainly by in vivo methods,
      however, recently enforced European legislations urge and promote the development
      of animal-free test methods able to predict chemical sensitizers. Recently, we
      presented a predictive biomarker signature in the myeloid cell line MUTZ-3, for
      assessment of skin sensitizers. The identified genomic biomarkers were found to
      be involved in immunologically relevant pathways, induced by recognition of
      foreign substances and regulating dendritic cell maturation and cytoprotective
      mechanisms. We have developed the usage of this biomarker signature into a novel
      in vitro assay for assessment of chemical sensitizers, called Genomic Allergen
      Rapid Detection (GARD). The assay is based on chemical stimulation of MUTZ-3
      cultures, using the compounds to be assayed as stimulatory agents. The readout of
      the assay is a transcriptional quantification of the genomic predictors,
      collectively termed the GARD Prediction Signature (GPS), using a complete genome
      expression array. Compounds are predicted as either sensitizers or nonsensitizers
      by a Support Vector Machine model. In this report, we provide a proof of concept
      for the functionality of the GARD assay by describing the classification of 26
      blinded and 11 nonblinded chemicals as sensitizers or nonsensitizers. Based on
      these classifications, the accuracy, sensitivity, and specificity of the assay
      were estimated to 89, 89, and 88%, respectively. 

PMID- 24675088
TI  - An integrated characterization of serological, pathological, and functional
      events in doxorubicin-induced cardiotoxicity.
AB  - Many efficacious cancer treatments cause significant cardiac morbidity, yet
      biomarkers or functional indices of early damage, which would allow monitoring
      and intervention, are lacking. In this study, we have utilized a rat model of
      progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple
      approaches, including cardiac magnetic resonance imaging (MRI), to provide the
      most comprehensive characterization to date of the timecourse of serological,
      pathological, and functional events underlying this toxicity. Hannover Wistar
      rats were dosed with 1.25 mg/kg DOX weekly for 8 weeks followed by a 4 week off
      dosing "recovery" period. Electron microscopy of the myocardium revealed
      subcellular degeneration and marked mitochondrial changes after a single dose.
      Histopathological analysis revealed progressive cardiomyocyte degeneration,
      hypertrophy/cytomegaly, and extensive vacuolation after two doses. Extensive
      replacement fibrosis (quantified by Sirius red staining) developed during the off
      dosing period. Functional indices assessed by cardiac MRI (including left
      ventricular ejection fraction (LVEF), cardiac output, and E/A ratio) declined
      progressively, reaching statistical significance after two doses and culminating
      in "clinical" LV dysfunction by 12 weeks. Significant increases in peak
      myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged
      after eight doses, importantly preceding the LVEF decline to <50%. Troponin I
      levels positively correlated with delayed and peak gadolinium contrast
      enhancement, histopathological grading, and diastolic dysfunction. In summary,
      subcellular cardiomyocyte degeneration was the earliest marker, followed by
      progressive functional decline and histopathological manifestations. Myocardial
      contrast enhancement and elevations in cTnI occurred later. However, all indices
      predated "clinical" LV dysfunction and thus warrant further evaluation as
      predictive biomarkers. 

PMID- 24675089
TI  - Food emulsifier polysorbate 80 increases intestinal absorption of di-(2
      ethylhexyl) phthalate in rats.
AB  - The aim of the present research was to explore whether food emulsifier
      polysorbate 80 can enhance the absorption of di-(2-ethylhexyl) phthalate (DEHP)
      and its possible mechanism. We established the high-performance liquid
      chromatography (HPLC) method for detecting DEHP and its major metabolite, mono
      ethylhexyl phthalate (MEHP) in rat plasma, and then examined the toxicokinetic
      and bioavailability of DEHP with or without polysorbate 80 in rats. The study of
      its mechanism to increase the absorption of phthalates demonstrated that
      polysorbate 80 can induce mitochondrial dysfunction in time- and concentration
      dependence manners in Caco-2 cells by reducing mitochondrial membrane potential,
      diminishing the production of the adenosine triphosphate, and decreasing the
      activity of electron transport chain. Our results indicated that food emulsifier
      applied in relatively high concentrations in even the most frequently consumed
      foods can increase the absorption of DEHP, and its role may be related to the
      structure and function damages of mitochondria in enterocytes. 

PMID- 24675090
TI  - Genetic or pharmacologic activation of Nrf2 signaling fails to protect against
      aflatoxin genotoxicity in hypersensitive GSTA3 knockout mice.
AB  - Mice are resistant to aflatoxin hepatotoxicity, primarily due to high expression
      of glutathione S-transferases (GSTs), and in particular the GSTA3 subunit.
      Nuclear factor erythroid 2 related factor 2 (Nrf2) signaling, which controls a
      broad-based cytoprotective response, was activated either genetically or
      pharmacologically in an attempt to rescue GSTA3 knockout mice from aflatoxin
      genotoxicity. Genetic activation of Nrf2 signaling was attained in a GSTA3:
      hepatocyte-specific Keap1 double knockout (DKO) mouse whereas pharmacologic
      activation of Nrf2 was achieved through pretreatment of mice with the
      triterpenoid 1-[2-cyano-3-,12-dioxoleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im)
      prior to aflatoxin B1 exposure. Following oral treatment with aflatoxin, urine
      was collected from mice for 24 h and hepatic and urinary aflatoxin metabolites
      then quantified using isotope dilution-mass spectrometry. Although Nrf2 was
      successfully activated genetically and pharmacologically, neither means affected
      the response of GSTA3 knockout mice to chemical insult with aflatoxin. Hepatic
      aflatoxin B1-N(7)-guanine levels were elevated 120-fold in GSTA3 knockout mice
      compared with wild-type and levels were not attenuated by the interventions. This
      lack of effect was mirrored in the urinary excretion of aflatoxin B1-N(7)
      guanine. By contrast, urinary excretion of aflatoxin B1-N-acetylcysteine was >200
      fold higher in wild-type mice compared with the single GSTA3 knockout or DKO
      mouse. The inability to rescue GSTA3 knockout mice from aflatoxin genotoxicity
      through the Nrf2 transcriptional program indicates that Gsta3 is unilaterally
      responsible for the detoxication of aflatoxin in mice. 

PMID- 24675091
TI  - Nuclear proteomics with XRCC3 knockdown to reveal the development of doxorubicin
      resistant uterine cancer.
AB  - The nucleus is a key organelle in mammary cells, which is responsible for several
      cellular functions including cell proliferation, gene expression, and cell
      survival. In addition, the nucleus is the primary targets of doxorubicin
      treatment. In the current study, low-abundance nuclear proteins were enriched for
      proteomic analysis by using a state-of-the-art two-dimensional differential gel
      electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the
      nuclear protein profiling changes responsible for the development of doxorubicin
      resistance in human uterine cancer cells. The results of the nuclear proteomic
      analysis indicated that more than 2100 protein features were resolved from an
      equal pooled amount of three purified nuclear proteins and 117 differentially
      expressed spots were identified. Of these 117 identified proteins, 48 belonged to
      nuclear proteins and a positive correlation was observed between the expression
      levels of 32 of these nuclear proteins and an increase in drug resistance.
      According to our review of relevant research, nuclear proteins such as DNA repair
      protein XRCC3 (XRCC3) have not been reported to play roles in the formation of
      doxorubicin resistance. Previous studies have used RNA interference and cell
      viability analysis to evidence the essential roles of XRCC3 on its potency in the
      formation of doxorubicin resistance. To sum up, our nuclear proteomic approaches
      enabled us to identify numerous proteins, including XRCC3, involved in various
      drug-resistance-forming mechanisms. Our results provide potential diagnostic
      markers and therapeutic candidates for treating doxorubicin-resistant uterine
      cancer. 

PMID- 24675092
TI  - Transcriptomic analyses of neurotoxic effects in mouse brain after intermittent
      neonatal administration of thimerosal.
AB  - Thimerosal is a vaccine antimicrobial preservative which has long been suspected
      an iatrogenic factor possibly contributing to neurodevelopmental disorders
      including autism. The association between infant vaccine thimerosal exposure and
      autism remains an open question. Although thimerosal has been removed from
      mandatory childhood vaccines in the United States, thimerosal-preserved vaccines
      are still widely used outside of the United States especially in developing
      countries. Notably, thimerosal-containing vaccines are being given to the
      newborns within the first 12-24 h after birth in some countries. To examine the
      possible neurotoxic effects of early neonatal exposure to a higher level of
      thimerosal, FVB mice were subcutaneously injected with thimerosal-mercury at a
      dose which is 20* higher than that used for regular Chinese infant immunization
      during the first 4 months of life. Thimerosal-treated mice exhibited neural
      development delay, social interaction deficiency, and inclination of depression.
      Apparent neuropathological changes were also observed in adult mice neonatally
      treated with thimerosal. High-throughput RNA sequencing of autistic-behaved mice
      brains revealed the alternation of a number of canonical pathways involving
      neuronal development, neuronal synaptic function, and the dysregulation of
      endocrine system. Intriguingly, the elevation of anterior pituitary secreting
      hormones occurred exclusively in male but not in female thimerosal-treated mice,
      demonstrating for the first time the gender bias of thimerosal-mercury toxicity
      with regard to endocrine system. Our results indicate that higher dose of
      neonatal thimerosal-mercury (20* higher than that used in human) is capable of
      inducing long-lasting substantial dysregulation of neurodevelopment, synaptic
      function, and endocrine system, which could be the causal involvements of
      autistic-like behavior in mice. 

PMID- 24675093
TI  - Chemical allergen induced perturbations of the mouse lymph node DNA methylome.
AB  - Epigenetic regulation of gene expression plays a pivotal role in the
      orchestration of immune responses and may determine the vigor, quality, or
      longevity of such responses. Chemical allergens can be divided into two
      categories: skin sensitizing chemicals associated with allergic contact
      dermatitis, and chemicals that cause sensitization of the respiratory tract and
      occupational asthma. In mice, these are characterized by different T helper cell
      responses. To explore the regulation and maintenance of these divergent
      responses, mice were exposed to 2,4-dinitrochlorobenzene (DNCB, a contact
      allergen) or trimellitic anhydride (TMA, a respiratory allergen). DNA from
      draining lymph nodes was processed for methylated DNA immunoprecipitation
      followed by hybridization to a whole-genome DNA promoter array. 6319 differently
      methylated regions (DMRs) were identified following DNCB treatment, whereas 2178
      DMRs were measured following TMA treatment, with approximately half of the TMA
      DMRs common to DNCB. When limited to promoter region-associated DMRs, 637 genes
      were uniquely associated with DNCB-induced DMRs but only 164 genes were unique to
      TMA DMRs. Promoter-associated DMRs unique to either DNCB or TMA were generally
      hypomethylated whereas DMRs common to both allergens tended to be
      hypermethylated. Pathway analyses highlighted a number of immune-related
      pathways, including chemokine and cytokine signaling. These data demonstrate that
      chemical allergen exposure results in characteristic patterns of DNA methylation
      indicative of epigenetic regulation of the allergic response. 

PMID- 24675094
TI  - Prenatal arsenic exposure and shifts in the newborn proteome: interindividual
      differences in tumor necrosis factor (TNF)-responsive signaling.
AB  - Exposure to inorganic arsenic (iAs) early in life is associated with adverse
      health effects in infants, children, and adults, and yet the biological
      mechanisms that underlie these effects are understudied. The objective of this
      research was to examine the proteomic shifts associated with prenatal iAs
      exposure using cord blood samples isolated from 50 newborns from Gomez Palacio,
      Mexico. Levels of iAs in maternal drinking water (DW-iAs) and the sum of iAs and
      iAs metabolites in maternal urine (U-tAs) were determined. Cord blood samples
      representing varying iAs exposure levels during the prenatal period (DW-iAs
      ranging from <1 to 236 MUg As/l) were analyzed for altered expression of proteins
      associated with U-tAs using a high throughput, antibody-based method. A total of
      111 proteins were identified that had a significant association between protein
      level in newborn cord blood and maternal U-tAs. Many of these proteins are
      regulated by tumor necrosis factor and are enriched in functionality related to
      immune/inflammatory response and cellular development/proliferation.
      Interindividual differences in proteomic response were observed in which 30
      newborns were "activators," displaying a positive relationship between protein
      expression and maternal U-tAs. For 20 "repressor" newborns, a negative
      relationship between protein expression level and maternal U-tAs was observed.
      The activator/repressor status was significantly associated with maternal U-tAs
      and head circumference in newborn males. These results may provide a critical
      groundwork for understanding the diverse health effects associated with prenatal
      arsenic exposure and highlight interindividual responses to arsenic that likely
      influence differential susceptibility to adverse health outcomes. 

PMID- 24675096
TI  - Ultrasound detected synovial change and pain response following intra-articular
      injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: a
      pilot study.

PMID- 24675095
TI  - Knockdown of a zebrafish aryl hydrocarbon receptor repressor (AHRRa) affects
      expression of genes related to photoreceptor development and hematopoiesis.
AB  - The aryl hydrocarbon receptor repressor (AHRR) is a transcriptional repressor of
      aryl hydrocarbon receptor (AHR) and hypoxia-inducible factor (HIF) and is
      regulated by an AHR-dependent mechanism. Zebrafish (Danio rerio) possess two AHRR
      paralogs; AHRRa regulates constitutive AHR signaling during development, whereas
      AHRRb regulates polyaromatic hydrocarbon-induced gene expression. However, little
      is known about the endogenous roles and targets of AHRRs. The objective of this
      study was to elucidate the role of AHRRs during zebrafish development using a
      loss-of-function approach followed by gene expression analysis. Zebrafish embryos
      were microinjected with morpholino oligonucleotides against AHRRa or AHRRb to
      knockdown AHRR protein expression. At 72 h postfertilization (hpf), microarray
      analysis revealed that the expression of 279 and 116 genes was altered by
      knockdown of AHRRa and AHRRb, respectively. In AHRRa-morphant embryos, 97 genes
      were up-regulated and 182 genes were down-regulated. Among the down-regulated
      genes were several related to photoreceptor function, including cone-specific
      genes such as several opsins (opn1sw1, opn1sw2, opn1mw1, and opn1lw2),
      phosphodiesterases (pde6H and pde6C), retinol binding protein (rbp4l), phosducin,
      and arrestins. Down-regulation was confirmed by RT-PCR and with samples from an
      independent experiment. The four genes tested (opn1sw1, pde6H, pde6C, and arr3b)
      were not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin. AHRRa knockdown also
      caused up-regulation of embryonic hemoglobin (hbbe3), suggesting a role for AHRR
      in regulating hematopoiesis. Knockdown of AHRRb caused up-regulation of 31 genes
      and down-regulation of 85 genes, without enrichment for any specific biological
      process. Overall, these results suggest that AHRRs may have important roles in
      development, in addition to their roles in regulating xenobiotic signaling. 

PMID- 24675097
TI  - The role of T helper 17 cell subsets in Sjogren's syndrome: similarities and
      differences between mouse model and humans.

PMID- 24675098
TI  - Retracted: Methotrexate in the treatment of symptomatic knee osteoarthritis:
      randomised placebo-controlled trial.
AB  - This article has been retracted.

PMID- 24675099
TI  - Dynamics and thermodynamics of polymer glasses.
AB  - The fate of matter when decreasing the temperature at constant pressure is that
      of passing from gas to liquid and, subsequently, from liquid to crystal. However,
      a class of materials can exist in an amorphous phase below the melting
      temperature. On cooling such materials, a glass is formed; that is, a material
      with the rigidity of a solid but exhibiting no long-range order. The study of the
      thermodynamics and dynamics of glass-forming systems is the subject of continuous
      research. Within the wide variety of glass formers, an important sub-class is
      represented by glass forming polymers. The presence of chain connectivity and, in
      some cases, conformational disorder are unfavourable factors from the point of
      view of crystallization. Furthermore, many of them, such as amorphous
      thermoplastics, thermosets and rubbers, are widely employed in many applications.
      In this review, the peculiarities of the thermodynamics and dynamics of glass
      forming polymers are discussed, with particular emphasis on those topics
      currently the subject of debate. In particular, the following aspects will be
      reviewed in the present work: (i) the connection between the pronounced slowing
      down of glassy dynamics on cooling towards the glass transition temperature (Tg)
      and the thermodynamics; and, (ii) the fate of the dynamics and thermodynamics
      below Tg. Both aspects are reviewed in light of the possible presence of a
      singularity at a finite temperature with diverging relaxation time and zero
      configurational entropy. In this context, the specificity of glass-forming
      polymers is emphasized. 

PMID- 24675100
TI  - Effects of di-(2-ethylhexyl) phthalate on the hypothalamus-pituitary-ovarian axis
      in adult female rats.
AB  - Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is
      widely present in the environment and some products with phthalate plasticizer.
      It has become a serious problem in recent years. The effect of DEHP on female
      reproductive system is still not well-studied. This study was to investigate the
      effects of DEHP on hypothalamus-pituitary-ovarian axis in adult female rats.
      Compared with control rats, the DEHP-treated rats showed: (1) lower body weight;
      (2) lower organ coefficient of ovary; (3) higher GnRH level in the hypothalamus;
      (4) higher mRNA and protein levels of GnRHR in the pituitary; and (5) lower serum
      sex hormone levels. Our data reveal that DEHP exposure may lead to the disruption
      of estrogen biosynthesis pathways in female rats and imbalance of hypothalamus
      pituitary-ovarian axis. DEHP may impose negative influence on the development and
      function of the reproductive system in female rats. 

PMID- 24675101
TI  - Commentary to 'Upper tract changes in patients with neurogenic bladder and
      sustained pressures >40 cm following bladder neck surgery without augmentation'.

PMID- 24675102
TI  - Two different dosages of nebulized steroid versus parenteral steroid in the
      management of COPD exacerbations: a randomized control trial.
AB  - BACKGROUND: The study aimed to compare the efficacy and safety of nebulized
      steroid (NS) with systemic corticosteroids (SC) and to determine optimal NS dose
      in the treatment of patients with COPD exacerbations requiring hospitalization.
      MATERIAL AND METHODS: The study was a randomized, parallel design trial. Eligible
      patients (n=86) were randomly allocated to 1 of the 3 treatment groups:
      parenteral corticosteroid (PS) (n=33), 4 mg (NB) (n=27), or 8 mg NB (n=26).
      Partial pressure of arterial oxygen (PaO2), carbon dioxide (PaCO2), pH, and
      oxygen saturation (SaO2) were evaluated at baseline, 24 h, 48 h, and discharge.
      Airway obstruction (forced vital capacity [FVC] and forced expiratory volume 1 s
      [FEV1]) was evaluated at admission and discharge. RESULTS: There were no
      significant differences between the groups for all parameters at all time
      periods, except for higher FEV1 value in the 8-mg NB group at baseline. In
      groups, significant differences were determined for FVC, FEV1, PaO2, and SaO2
      (p<0.001), but not for PaCO2 and pH, in comparison to their baseline values. As
      adverse events, hyperglycemia and oral moniliasis were observed in the PS group
      (n=4) and in the NB groups (n=5), respectively, and treatment change was required
      in 9 patients (2 patients in the PS group and 7 patients in the NB groups)
      (p=0.57). CONCLUSIONS: Nebulized budesonide may be used as an alternative to SC
      because of its equal effectiveness and lesser systemic adverse effects. The
      choice of optimal dosage needs to be evaluated carefully because adverse effect
      and dropout rates varied according to dosage. However, there is a need for
      further studies including more severe cases and evaluating long-term outcomes or
      relapses comparing the 3 arms.

PMID- 24675103
TI  - Secreted frizzled-related protein 4 (SFRP4) and fractalkine (CX3CL1) - Potential
      new biomarkers for beta-cell dysfunction and diabetes.
AB  - The discovery of new risk factors for diabetes is a major challenge for
      contemporary science. Pathogenesis of type 2 diabetes mellitus (T2DM) is closely
      related to adipose tissue dysfunction. The aim of this review was to describe
      recently discovered cytokines: fractalkine (CX3CL1, FKN) and secreted frizzled
      related protein 4 (SFRP4) as potential biomarkers of early beta cell dysfunction
      and diabetes. The association of CX3CL1 and SFRP4 with low-grade inflammation in
      adipose tissue links obesity with disturbances in insulin secretion and impaired
      glucose metabolism, therefore it indicates new therapeutic and preventive targets
      in both healthy and diabetic subjects. 

PMID- 24675104
TI  - [Allergy to pine processionary moth larvae].

PMID- 24675105
TI  - Altered expression of tumor suppressor PHF20 in myeloproliferative neoplasms.

PMID- 24675107
TI  - Homogeneous barrier modulation of TaOx/TiO2 bilayers for ultra-high endurance
      three-dimensional storage-class memory.
AB  - Three-dimensional vertical resistive-switching random access memory (VRRAM) is
      the most anticipated candidate for fulfilling the strict requirements of the
      disruptive storage-class memory technology, including low bit cost, fast access
      time, low-power nonvolatile storage,and excellent endurance. However, an
      essential self-selecting resistive-switching cell that satisfies these
      requirements has yet to be developed. In this study, we developed a TaOx/TiO2
      double-layer V-RRAM containing numerous highly desired features, including: (1) a
      self-rectifying ratio of up to 103 with a sub-MUA operating current, (2) little
      cycle-to-cycle and layer-to-layer variation, (3) a steep vertical sidewall
      profile for high-density integration, (4) forming-free and self-compliance
      characteristics for a simple peripheral circuit design, and (5) an extrapolated
      endurance of over 1015 cycles at 100  degrees C. Furthermore, the switching and
      self-rectifying mechanisms were successfully modeled using oxygen ion migration
      and homogeneous barrier modulation. We also suggest the new possibility of
      monolithically integrating working and storage memory by exploiting a unique
      tradeoff between retention time and endurance.

PMID- 24675106
TI  - Leukemic stem cells of acute myeloid leukemia patients carrying NPM1 mutation are
      candidates for targeted immunotherapy.

PMID- 24675108
TI  - Scaffolds for tissue engineering of cardiac valves.
AB  - Tissue engineered heart valves offer a promising alternative for the replacement
      of diseased heart valves avoiding the limitations faced with currently available
      bioprosthetic and mechanical heart valves. In the paradigm of tissue engineering,
      a three-dimensional platform - the so-called scaffold - is essential for cell
      proliferation, growth and differentiation, as well as the ultimate generation of
      a functional tissue. A foundation for success in heart valve tissue engineering
      is a recapitulation of the complex design and diverse mechanical properties of a
      native valve. This article reviews technological details of the scaffolds that
      have been applied to date in heart valve tissue engineering research. 

PMID- 24675109
TI  - Differential responses of Arabidopsis thaliana accessions to atmospheric nitrogen
      dioxide at ambient concentrations.
AB  - To better understand the response of plants to atmospheric nitrogen dioxide
      (NO2), we investigated biomass accumulation in 3 accessions of Arabidopsis
      thaliana: C24, Columbia (Col-0), and Landsberg erecta (Ler). Plants were grown in
      NO2-free air for 1 week after sowing, followed by 3 (Col-0 and Ler) to 4 (C24)
      weeks in air with or without NO 2 (10 or 50 ppb). NO2 treatment increased the
      biomass of all 3 accessions to varying extents. Treatment with 10 ppb NO2
      increased shoot biomass in C24, Col-0, and Ler by 3.2-, 1.4-, and 2.3-fold,
      respectively, compared with control. Treatment with 50 ppb gave similar
      increases, except in C24 (2.7-fold). The physiological, evolutionary, and genetic
      significance of these results are discussed below.

PMID- 24675110
TI  - Ketogenic diet in adolescents and adults with epilepsy.
AB  - PURPOSE: The ketogenic diet is an alternative treatment for patients with
      refractory epilepsy. Most studies to date report dietary response in children.
      There are limited data evaluating the efficacy of the ketogenic diet in adults.
      This is a report of the long-term outcome in a largely adult population of
      patients treated with the ketogenic diet for epilepsy. METHOD: Twenty-nine adult
      and adolescent patients (mean age 32 years, range 11-51) were initiated on the
      ketogenic diet and followed until diet discontinuation. Clinical response and
      adverse effects were noted during the duration of the diet. RESULTS: Fifty-two
      percent of patients had a significant reduction in seizure frequency on the
      ketogenic diet, including 45% with >=50% reduction in seizure frequency. Thirty
      one percent had no improvement, seven percent were unable to successfully
      initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was
      continued for a mean of 9 months (range 0.13-35 months), with five patients
      completing >=23 months. There was a trend toward better response and better
      tolerability/longer duration in patients with symptomatic generalized epilepsy.
      The diet was generally well-tolerated, but undesired weight loss and constipation
      were the most frequent adverse effects. CONCLUSION: The ketogenic diet can be
      used safely in the adult and adolescent population, with a response rate similar
      to those seen in children. Patient with symptomatic generalized epilepsy may be
      particularly good candidates for this type of dietary treatment.

PMID- 24675111
TI  - Deep brain stimulation for the management of seizures in MECP2 duplication
      syndrome.

PMID- 24675112
TI  - Rich and rewarding.

PMID- 24675113
TI  - Considerations for single-subject research designs.

PMID- 24675114
TI  - Plyometric training: effectiveness and optimal duration for children with
      unilateral cerebral palsy.
AB  - PURPOSE: To evaluate the optimal duration and effects of plyometric training on
      the gross motor abilities of 3 boys with unilateral spastic cerebral palsy (9
      years 11 months, 10 years, and 8 years 9 months). METHODS: This was a multiple
      baseline, multiple-probe, single-subject experiment. The intervention followed
      the National Strength and Conditioning Association's guidelines for youth. The
      Gross Motor Function Measure 66, 10*5-m sprint, 20-m run, throw ball, broad jump,
      and vertical jump tests were used to evaluate gross motor abilities, agility,
      running speed, and power. RESULTS: Improvements were found in upper extremity
      power, Gross Motor Function Measure 66 scores, and agility. Findings for lower
      extremity power and running speed were inconsistent. Training duration ranged
      from 8 to 14 weeks. CONCLUSIONS: This study suggests that plyometric training
      improves gross motor ability, agility, and upper extremity power in boys with
      unilateral cerebral palsy. Treatment duration should be determined by an
      individual's capacity, the task, and the outcome measure.

PMID- 24675115
TI  - Commentary on "plyometric training: effectiveness and optimal duration for
      children with unilateral cerebral palsy".

PMID- 24675116
TI  - Reliability and diagnostic accuracy of clinical tests of vestibular function for
      children.
AB  - PURPOSE: To determine reliability, diagnostic values, and minimal detectable
      change scores, 90% confidence (MDC90) of pediatric clinical tests of vestibular
      function. METHODS: Twenty children with severe to profound bilateral
      sensorineural hearing loss and 23 children with typical development, aged 6 to 12
      years, participated. The Head Thrust Test, Emory Clinical Vestibular Chair Test,
      Bucket Test, Dynamic Visual Acuity, Modified Clinical Test of Sensory Interaction
      on Balance, and Sensory Organization Test were completed twice for reliability.
      Reference standard diagnostic tests were rotary chair and vestibular evoked
      myogenic potential. Reliability, sensitivity, specificity, predictive values,
      likelihood ratios, and MDC90 scores were calculated. RESULTS: Reliability ranged
      from an intraclass correlation coefficient of 0.73 to 0.95. Sensitivity,
      specificity, and predictive values, using cutoff scores for each test
      representing the largest area under the curve, ranged from 63% to 100%. The MDC90
      for Dynamic Visual Acuity and Modified Clinical Test of Sensory Interaction on
      Balance were 8 optotypes and 16.75 seconds, respectively. CONCLUSIONS: Clinical
      tests can be used accurately to identify children with vestibular hypofunction.

PMID- 24675117
TI  - Commentary on "reliability and diagnostic accuracy of clinical tests of
      vestibular function for children".

PMID- 24675119
TI  - Commentary on "performance of high school adolescents on functional gait and
      balance measures".

PMID- 24675118
TI  - Performance of high school adolescents on functional gait and balance measures.
AB  - PURPOSE: To describe the performance of high school adolescents during common
      functional gait and balance measures used in vestibular physical therapy.
      METHODS: A cross-sectional study of 91 participants determined their performance
      on the Activities-specific Balance Confidence (ABC) scale, Dynamic Gait Index,
      Functional Gait Assessment, Timed "Up and Go" (TUG), Five Times Sit to Stand
      (FTSTS) test, tests of gait speed (GS), and the Balance Error Scoring System. In
      a subset of this sample, GS, TUG, and the FTSTS were repeated twice to examine
      test-retest reliability. RESULTS: The measures of GS, TUG, and FTSTS were
      normally distributed. The Activities-specific Balance Confidence, Dynamic Gait
      Index, and Functional Gait Assessment exhibited a ceiling effect. The timed
      measures exhibited moderate to good reliability. CONCLUSIONS: These performance
      scores may provide end points for discharge from vestibular physical therapy.
      However, clinicians should be aware of the ceiling effect exhibited by some
      measures.

PMID- 24675120
TI  - Measuring advanced motor skills in children with cerebral palsy: further
      development of the Challenge module.
AB  - PURPOSE: Since previous testing of the Challenge Module revealed that response
      scales should assess performance speed as well as skill accomplishment, this
      study sought to develop empirically based dual-criterion (accomplishment and
      time) response options. METHODS: Challenge items were tested with a convenience
      sample of 34 children who were typically developing (4-10 years) to obtain time
      cut-points that could be applied to children/youth with cerebral palsy.
      Median/lower quartile item performance times were calculated within younger (<7.5
      years) and older child (>=7.5 years) groups, and used as benchmarks for response
      option cut-points. Children's scores were recalculated using these cut-points to
      verify that differences in younger and older children's abilities and times were
      captured. RESULTS: Mean scores were 48.9% and 87.2% for younger and older groups,
      reflecting expected developmental progression. Further response revision captured
      high-level movement control older children exhibited. CONCLUSION: The revised
      Challenge measures skill accomplishment, speed, and quality.

PMID- 24675121
TI  - Commentary on "measuring advanced motor skills in children with cerebral palsy:
      further development of the challenge module".

PMID- 24675122
TI  - Early childrearing practices and their relationship to academic performance in
      Mexican American children.
AB  - PURPOSE: To examine whether parenting behaviors and childrearing practices in the
      first 3 years of life among Mexican American (MA) families predict children's
      academic performance at school age. METHODS: Thirty-six children were assessed
      using the Parent Behavior Checklist, Nursing Child Assessment Teaching Scale,
      Home Observation for Measurement of the Environment Inventory, and Bayley Scales
      of Infant Development II. Academic performance was measured with the Illinois
      Standards Achievement Test during third grade. RESULTS: Correlation between
      parents' developmental expectations, nurturing behaviors, discipline, and
      academic performance were statistically significant (P < .05). Developmental
      expectations and discipline strategies predicted 30% of the variance in the
      Illinois Standards Achievement Test of reading. CONCLUSIONS: The results of this
      study suggest that early developmental expectations that MA parents have for
      their children, and the nurturing and discipline behaviors they engage in, are
      related to how well the children perform on academic tests at school age.

PMID- 24675123
TI  - Commentary on "early childrearing practices and their relationship to academic
      performance in Mexican American children".

PMID- 24675124
TI  - Postural orientation during standing in children with bilateral cerebral palsy.
AB  - PURPOSE: To investigate postural orientation and maintenance of joint position
      during standing in children with bilateral spastic cerebral palsy (BSCP).
      METHODS: Standing was examined with 3-D motion analysis in 26 children with BSCP,
      and 19 children typically developing (TD). Two groups of children with cerebral
      palsy (CP) were analyzed: 15 who were able to maintain standing without support
      and 11 who needed support. RESULTS: Children with CP stood with more flexion than
      children TD. In the CP groups, children standing without support stood more
      asymmetrically with less hip and knee flexion and less movement than those who
      required support. CONCLUSION: Children with CP had varying abilities to stand and
      maintain standing posture with or without support. Both CP groups stood with more
      flexion than their potential passive joint angle, more obvious in children
      requiring support. Investigations on how muscle strength and spatial perception
      influence posture remains to be explored.

PMID- 24675125
TI  - Commentary on "postural orientation during standing in children with bilateral
      cerebral palsy".

PMID- 24675126
TI  - Normal values of functional reach and lateral reach tests in children with knee
      hypermobility.
AB  - PURPOSE: To measure values for functional reach (FR) and lateral reach (LR) in
      school children with knee joint hypermobility (KJH), and to examine the
      correlation of anthropometric measures and KJH with FR and LR values. METHODS: A
      total of 140 children aged 6 to 12 years with typical development (TD) and
      bilateral KJH of greater than 10 degrees  hyperextension participated. Three
      successive trials of FR and LR tests in standing position with feet shoulder
      width apart were performed, and the mean of the 3 trials was calculated. Analysis
      of variance and Bonferroni tests were used to analyze correlation and association
      of FR and LR values with KJH angle and anthropometric data, respectively, with a
      95% confidence interval. RESULTS: In school-aged children with TD, height and KJH
      contributed significantly to the FR values in both genders, whereas height
      contributed for LR values among girls alone. CONCLUSIONS: Height and KJH affect
      children's scores on the FR and LR tests of balance.

PMID- 24675127
TI  - Commentary on "normal values of functional reach and lateral reach tests in
      children with knee joint hypermobility".

PMID- 24675128
TI  - Perceptions of equine-assisted activities and therapies by parents and children
      with spinal muscular atrophy.
AB  - PURPOSE: To identify the physical and psychosocial effects of equine-assisted
      activities and therapies (EAATs) on children with spinal muscular atrophy (SMA)
      from the perspective of the children and their parents. METHODS: The families of
      all eligible children with SMA, who reported participation in EAAT, from a
      Western metropolitan academic center were contacted and invited to participate.
      This study implemented qualitative, semistructured interviews of children with
      SMA and their parents. RESULTS: Three themes emerged from the qualitative content
      analysis: physical/psychosocial benefits; relationship development with the
      horses, instructors, and children; and barriers to continued EAAT engagement.
      CONCLUSIONS: The data suggest that the overall EAAT experience was a source of
      enjoyment, self-confidence, and normalcy for the children with SMA. The results
      of this study provide preliminary support for the use of EAAT among children with
      SMA.

PMID- 24675129
TI  - Commentary on: "perceptions of equine-assisted activities and therapies by
      parents and children with spinal muscular atrophy".

PMID- 24675130
TI  - Muscle strength, joint range of motion, and gait in children and adolescents with
      osteogenesis imperfecta.
AB  - PURPOSE: To analyze clinical and functional features of children and adolescents
      with osteogenesis imperfecta (OI). METHODS: A cross-sectional study of 62
      participants examined clinical, body structure and function and activity
      features. RESULTS: A total of 31 participants had OI type I, 9 had type III, and
      22 had type IV. Mild (type I) and moderate/severe (types III and IV) OI differed
      significantly in occurrence of fractures, presence of bone deformities, the use
      of intramedullary rods, bone mineral density, and bisphosphonate therapy. Age of
      gait acquisition showed an association with overall joint range of motion and an
      inverse relationship with overall muscle strength. Level of ambulation was
      associated with overall muscle strength and inversely associated with overall
      joint range of motion. CONCLUSIONS: Features vary according to OI type. Moderate
      and severe forms of OI are associated with greater functional limitation,
      influenced by fracture history, which negatively affects the acquisition and
      level of ambulation.

PMID- 24675131
TI  - Commentary on "muscle strength, joint range of motion, and gait in children and
      adolescents with osteogenesis imperfecta".

PMID- 24675132
TI  - Serial casting for neuromuscular flatfoot and vertical talus in an adolescent
      with hereditary spastic paraplegia.
AB  - PURPOSE: The purpose of this report is to explore assessment and serial casting
      intervention for painful rigid flatfoot deformities with vertical talus in an
      adolescent girl with hereditary spastic paraplegia who was nonambulatory. SUMMARY
      OF KEY POINTS: The participant's right foot underwent 2 phases of casting with
      correction first toward hindfoot inversion and then dorsiflexion. Because of a
      vertical talus, her left foot required an intermediate casting toward plantar
      flexion, inversion, and forefoot adduction prior to casting toward dorsiflexion.
      STATEMENT OF CONCLUSIONS: The patient improved despite the underlying progressive
      neuromuscular disorder. Pain ameliorated and she returned to supported standing
      and transfers. Spasticity decreased bilaterally and the flexibility of her foot
      deformities improved to allow orthotic fabrication in subtalar neutral. Results
      were maintained at 12 and 16 months. RECOMMENDATIONS FOR CLINICAL PRACTICE:
      Individualized multiphase serial casting requires further investigation with
      patients such as those with hereditary spastic paraplegia.

PMID- 24675133
TI  - Treadmill training for a child with spina bifida without functional ambulation.
AB  - PURPOSE: To describe and report the effect of an 8-week individualized,
      progressive, treadmill training program on the ambulatory ability of a 4-year-old
      child with myelomeningocele without functional ambulation. SUMMARY OF KEY POINTS:
      Heart rate and speed on the 2-minute walk test (2MWT) were used to individualize
      training. Ambulatory outcome measures taken at baseline, postintervention, and 6
      weeks postintervention included the 2MWT and the Timed "Up and Go" (TUG). The
      Pediatric Evaluation of Disability Index was used to measure functional mobility.
      Improvements were noted in ambulatory ability after training (2MWT, 64.10%; TUG,
      34.66%) and at the 6-week follow-up (2MWT, 58.97%; TUG, 34.24%). The Pediatric
      Evaluation of Disability Index showed no significant difference. CONCLUSION AND
      RECOMMENDATIONS: Use of an individualized treadmill training program may have
      improved the ambulatory skills of a preschooler with myelomeningocele. More
      rigorous studies are needed to determine the effects of treadmill training with
      the spina bifida population and identify optimal training parameters.

PMID- 24675134
TI  - Reinventing the adjustable bench for community-based research and practice.

PMID- 24675135
TI  - Design, synthesis and evaluation of novel diaryl urea derivatives as potential
      antitumor agents.
AB  - A novel series of diaryl ureas containing different linker groups were designed
      and synthesized. Their in vitro antitumor activity against MX-1, A375, HepG2,
      Ketr3 and HT-29 was evaluated using the standard MTT assay. Compounds having a
      rigid linker group such as vinyl, ethynyl and phenyl showed significant
      inhibitory activity against a variety of cancer cell lines. Specifically,
      compound 23 with a phenyl linker group demonstrated broad-spectrum antitumor
      activity with IC50 values of 5.17-6.46 MUM against five tested tumor cell lines.
      Compound 23 is more potent than reference drug sorafenib (8.27-15.2 MUM),
      representing a promising lead for further optimization. 

PMID- 24675136
TI  - Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G
      protein-protein interaction inhibitors.
AB  - Protein-protein interactions are critical for regulating the activity of
      translation initiation factors and multitude of other cellular process, and form
      the largest block of untapped albeit most challenging targets for drug
      development. 4EGI-1, (E/Z)-2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl)hydrazono)-3
      (2-nitrophenyl)propanoic acid, is a hit compound discovered in a screening
      campaign of small molecule libraries as an inhibitor of translation initiation
      factors eIF4E and eIF4G protein-protein interaction; it inhibits translation
      initiation in vitro and in vivo. A series of 4EGI-1-derived thiazol-2-yl
      hydrazones have been designed and synthesized in order to delineate the
      structural latitude and improve its binding affinity to eIF4E, and increase its
      potency in inhibiting the eIF4E/eIF4G interaction. Probing a wide range of
      substituents on both phenyl rings comprising the 3-phenylpropionic acid and 4
      phenylthiazolidine moieties in the context of both E- and Z-isomers of 4EGI-1 led
      to analogs with enhanced binding affinity and translation initiation inhibitory
      activities. 

PMID- 24675137
TI  - Chalcones with electron-withdrawing and electron-donating substituents:
      anticancer activity against TRAIL resistant cancer cells, structure-activity
      relationship analysis and regulation of apoptotic proteins.
AB  - In the present study, a series of 46 chalcones were synthesised and evaluated for
      antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA
      MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2),
      colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T
      lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2)
      group on ring A was the most potent and selective against cancer cells. The
      effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29
      cells were determined. The results showed that 20 apoptotic markers (Bad, Bax,
      Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21,
      Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up
      regulated or down regulated. 

PMID- 24675138
TI  - Estimated glomerular filtration rate and albuminuria: diagnosis, staging, and
      prognosis.
AB  - PURPOSE OF REVIEW: To describe the relationship between estimated glomerular
      filtration rate (eGFR), albuminuria, and important outcomes for patients with
      chronic kidney disease (CKD). The first part of the review presents the evidence
      linking eGFR and albuminuria to important clinical outcomes, and the second part
      highlights the importance of these risk relationships across multiple subgroups
      and in clinical risk prediction. RECENT FINDINGS: Investigators have used data
      from large population-based cohort studies and conducted collaborative meta
      analyses to definitively establish the relationship between eGFR, albuminuria,
      and adverse clinical outcomes. Recent systematic reviews have also highlighted
      the importance of these variables in predicting the risk of kidney failure and
      all-cause mortality. SUMMARY: eGFR and albuminuria are important independent risk
      factors for kidney failure, acute kidney injury, and all-cause or cardiovascular
      mortality. These relationships are independent of age, sex, race, or ethnicity.
      eGFR and albuminuria can be combined with other demographic variables to
      accurately predict the risk of kidney failure and should be measured concurrently
      to determine diagnosis, staging, and prognosis in patients with CKD.

PMID- 24675139
TI  - Histopathological classification of antineutrophil cytoplasmic antibody
      associated glomerulonephritis: an update.
AB  - PURPOSE OF REVIEW: This review discusses the findings of studies validating the
      histopathological classification of antineutrophil cytoplasmic antibody (ANCA)
      associated glomerulonephritis, which was devised in 2010 by an international
      working group of pathologists and nephrologists in collaboration with the
      European Vasculitis Society. RECENT FINDINGS: So far, eight studies have
      validated the histopathological classification of ANCA-associated
      glomerulonephritis. The studies came from Japan, China, Australia, the United
      States, the Netherlands, and Turkey. These validation studies confirmed that the
      histopathological classification of ANCA-associated glomerulonephritis is of
      predictive value for renal outcome. This was especially the case for patients
      with either a focal or sclerotic-class renal biopsy, whereas the crescentic and
      mixed classes showed different results in the validation studies. These
      differences could be due to differences in patient populations or therapy, inter
      rater reliability and lack of inclusion of tubulointerstitial lesions in the
      classification. Therapy is known to influence renal outcome, but due to the
      retrospective design of the to-date performed validation studies, this parameter
      could not be fully accounted for in these validation studies. Inter-rater
      reliability among three histopathologists was investigated in one study and was
      moderate. SUMMARY: The histopathological classification of ANCA-associated
      glomerulonephritis predicts renal outcome during follow-up, especially in
      patients with a focal or sclerotic-class renal biopsy. A large international
      validation study is currently being performed. VIDEO ABSTRACT:
      http://links.lww.com/CONH/A6.

PMID- 24675140
TI  - Dimethyl alpha-ketoglutarate inhibits maladaptive autophagy in pressure overload
      induced cardiomyopathy.
AB  - It has been a longstanding problem to identify specific and efficient
      pharmacological modulators of autophagy. Recently, we found that depletion of
      acetyl-coenzyme A (AcCoA) induced autophagic flux, while manipulations designed
      to increase cytosolic AcCoA efficiently inhibited autophagy. Thus, the cell
      permeant ester dimethyl alpha-ketoglutarate (DMKG) increased the cytosolic
      concentration of alpha-ketoglutarate, which was converted into AcCoA through a
      pathway relying on either of the 2 isocitrate dehydrogenase isoforms (IDH1 or
      IDH2), as well as on ACLY (ATP citrate lyase). DMKG inhibited autophagy in an
      IDH1-, IDH2- and ACLY-dependent fashion in vitro, in cultured human cells.
      Moreover, DMKG efficiently prevented autophagy induced by starvation in vivo, in
      mice. Autophagy plays a maladaptive role in the dilated cardiomyopathy induced by
      pressure overload, meaning that genetic inhibition of autophagy by heterozygous
      knockout of Becn1 suppresses the pathological remodeling of heart muscle
      responding to hemodynamic stress. Repeated administration of DMKG prevents
      autophagy in heart muscle responding to thoracic aortic constriction (TAC) and
      simultaneously abolishes all pathological and functional correlates of dilated
      cardiomyopathy: hypertrophy of cardiomyocytes, fibrosis, dilation of the left
      ventricle, and reduced contractile performance. These findings indicate that DMKG
      may be used for therapeutic autophagy inhibition.

PMID- 24675141
TI  - Pre-existing cardiovascular conditions and high altitude travel. Consensus
      statement of the Medical Commission of the Union Internationale des Associations
      d'Alpinisme (UIAA MedCom) Travel Medicine and Infectious Disease.
AB  - The number of persons visiting high altitude regions for various purposes
      (recreation, business etc.), and the age of people who do so, increases.
      Therefore there are more and more patients who need specific and individual
      advice to prevent emergency situations at altitude and to deal with emergencies
      if the safety strategy should fail. Since literature concerning cardiocirculatory
      diseases at altitude is scarce and studies with a controlled setting and high
      evidence level are missing, UIAA MedCom has checked all available literature for
      specific information to enable physicians who are active in travel or high
      altitude medicine to advise the patients at the highest possible level of
      evidence. It must be pointed out that there are several other medical fields
      where such information is mandatory, e.g. in occupational medicine, when
      employees depart to high altitude destinations for business purposes. The
      recommendations are based on a detailed literature research (databases, handbooks
      and the respective references). For easier use the paper has been structured as
      follows: general information, cardiocirculatory system and ECG at altitude,
      several cardiocirculatory diseases and their specific recommendations. The
      commission concludes, that a general "don't go!" is no state-of-the-art advice
      for the patients. With the information presented here a safe trip to altitude
      should be possible for many patients. 

PMID- 24675142
TI  - Turner syndrome and meningioma: support for a possible increased risk of
      neoplasia in Turner syndrome.
AB  - Neoplasia is uncommon in Turner syndrome, although there is some evidence that
      brain tumors are more common in Turner syndrome patients than in the general
      population. We describe a woman with Turner syndrome (45,X) with a meningioma, in
      whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed
      five years later in the absence of therapeutic radiation. Together with 7 cases
      of Turner syndrome with meningioma from a population-based survey in the United
      Kingdom, and 3 other isolated cases in the literature, we review this small
      number of patients for evidence of risk factors related to Turner syndrome, such
      as associated structural anomalies or prior treatment. We performed histological
      and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the
      meningeal tumor to search for possible molecular determinants. We are not able to
      prove causation between these two entities, but suggest that neoplasia may be a
      rare associated medical problem in Turner syndrome. Additional case reports and
      extension of population-based studies are needed.

PMID- 24675143
TI  - Multimodal label-free detection and discrimination for small molecules using a
      nanoporous resonator.
AB  - To detect chemical or biological threats, it is crucial that sensor devices can
      differentiate various target molecules. In general, each different sensing method
      has its own strengths and weaknesses due to their respective limitations. For
      example, although resonant sensors have high sensitivity, they are not able to
      discriminate target molecules. At the same time, although surface-enhanced Raman
      spectroscopy is a representative label-free detection method that can
      discriminate target molecules, its fabrication is often complex and expensive.
      Here we present a label-free multimodal nanoporous resonator-based system for
      small molecule detection and discrimination that combines the strengths of each
      of these sensing methods. Our approach is not only able to improve the
      sensitivity of the resonant sensor but it can also discriminate the target
      molecules. Furthermore, the fabrication process is swift (lasting <3 min) and
      convenient. 

PMID- 24675144
TI  - European Journal of Vascular and Endovascular Surgery in the era of social media.

PMID- 24675145
TI  - Compression therapy versus surgery in the treatment of patients with varicose
      veins: A RCT.
AB  - OBJECTIVE: Superficial venous reflux and varicose veins are common. The aim of
      this randomized controlled trial was to assess effectiveness of compression
      therapy compared with surgery for superficial venous reflux. METHODS: 153
      patients with CEAP class C2-C3 and superficial venous reflux were randomized to
      receive either conservative treatment (compression stockings) (n = 77) or surgery
      (n = 76). Clinical examination including duplex ultrasound (DUS) was performed at
      entry and 1 and 2 years after randomization (compression group) or surgery
      (surgery group). Venous Clinical Severity Score without compression stockings
      (VCSS-S), Venous Segmental Disease Score (VSDS), Venous Disability Score (VDS),
      and health-related quality of life (HRQoL) were assessed at entry and at the
      follow-ups. Data were analysed on an intention-to-treat basis and according to
      the actual treatment performed. RESULTS: At 2 years, 70/76 patients in the
      surgery group and 11/77 patients in the compression group had been operated on.
      VCSS-S decreased from 4.6 to 3.5 in the compression group (p < .01) and from 4.8
      to 0.6 in the surgery group (p < .001). VSDS decreased from 7.7 to 7.0 in the
      compression group and from 8.2 to 0.9 in the surgery group (p < .0001). HRQoL did
      not change in the compression group, but improved significantly in the surgery
      group. CONCLUSION: The surgical elimination of non-complicated superficial venous
      reflux is an effective treatment when compared with providing compression
      stockings only.

PMID- 24675146
TI  - Simultaneous detection of Cherry necrotic rusty mottle virus and Cherry green
      ring mottle virus using real-time PCR and high resolution melting analysis.
AB  - In this study, the real-time PCR assays were combined with high resolution
      melting (HRM) analysis for the simultaneous detection of Cherry necrotic rusty
      mottle virus (CNRMV) and Cherry green ring mottle virus (CGRMV) infection in
      sweet cherry trees. Detection of CNRMV and CGRMV was performed in a real-time PCR
      using a primer set for both of them or duplex real-time PCR that included one
      specific primer set for each virus. These two strategies allowed us to confirmed
      virus infection in all tested samples. In 17 field samples the technique revealed
      samples positive for CNRMV or CGRMV as well as positive for both viruses. In
      addition, the HRM analysis made it possible to differentiate clearly between
      CNRMV and CGRMV. Sequence variations among CNRMV and CGRMV isolates observed from
      the HRM peaks were confirmed by sequencing. To test the capability to use this
      method in field, forty one sweet cherry samples were examined by HRM analysis.
      The HRM data showed that seven samples were positive for CNRMV and three were
      infected with CGRMV. The results presented in this study indicated that real-time
      PCR followed by HRM analysis provides sensitive, automated and rapid tool to
      detect and differentiate between CNRMV and CGRMV isolates.

PMID- 24675147
TI  - Cloning of a novel specific SCAR marker for species identification in
      Lactobacillus pentosus.
AB  - Identifying Lactobacillus species using only phenotypic and genotypic (16S rDNA
      sequence analysis) techniques yields inaccurate results. The objective of this
      study was to develop species-specific primers based on randomly amplified
      polymorphic DNA (RAPD) fingerprinting to distinguish species within the closely
      related Lactobacillus plantarum group. One of these primers, OPD-3, produced a
      species-specific band that was found only in the tested Lactobacillus pentosus.
      This specific fragment was isolated from agarose gel and ligated into a vector
      for DNA sequencing. A pair of primers, SpOPD3Lpen-F1/R1, that were highly
      specific sequence-characterized-amplified-regions (SCARs) were designed according
      to the nucleotide sequences of the specific RAPD marker. These primers were used
      for PCR analysis of the template DNA of the Lactobacillus strains, and a single
      542 bp species-specific band was found only in L. pentosus. Using PCR, a novel
      species-specific primer pair is shown to rapidly, accurately and effectively
      distinguish L. pentosus from other species in the L. plantarum group of probiotic
      bacteria.

PMID- 24675148
TI  - The FTO gene polymorphism (rs9939609) is associated with metabolic syndrome in
      morbidly obese subjects from southern Italy.
AB  - Gene variants in MC4R, SIRT1 and FTO are associated with severe obesity and
      metabolic impairment in Caucasians. We investigated whether common variants in
      these genes are associated with metabolic syndrome (MetS) in a large group of
      morbidly obese young adults from southern Italy. One thousand morbidly obese
      subjects (62% women, mean body mass index 46.5 kg/m(2), mean age 32.6 years)
      whose families had lived in southern Italy for at least 2 generations were
      recruited. Single-nucleotide polymorphisms (SNPs) rs12970134, rs477181, rs502933
      (MC4R locus), rs3818292, rs7069102, rs730821, rs2273773, rs12413112 (SIRT1 locus)
      and rs1421085, rs9939609, 9930506, 1121980 (FTO locus) were genotyped by Taqman
      assay; blood parameters were assayed by routine methods; the Fat Mass, Fat Free
      Mass, Respiratory Quotient, Basal Metabolic Rate (BMR) and waist circumference
      were also determined. Binomial logistic regression showed that the TA
      heterozygous genotype of SNP rs9939609 in the FTO gene was associated with the
      presence of MetS in our population [OR (95% CI): 2.53 (1.16-5.55)]. Furthermore,
      the FTO rs9939609 genotype accounted for 21.3% of the MetS phenotype together
      with total cholesterol, BMR and age. Our results extend the knowledge on genotype
      susceptibility for MetS in relation to a specific geographical area of residence.

PMID- 24675149
TI  - Modulation of methamphetamine's locomotor stimulation and self-administration by
      JHW 007, an atypical dopamine reuptake blocker.
AB  - JHW 007 [N-(n-butil)-3alpha-[bis(4'-fluorophenil)methoxi]-tropane] belongs to the
      family of N-substituted benztropine (BZT) analogs, atypical dopamine transporter
      (DAT) blockers that are able to strongly modulate cocaine- and amphetamine
      related behavior. In the present study, we tested in rats the ability of JHW 007
      to alter the stimulant and reinforcing properties of methamphetamine (METH) using
      locomotor activity, fixed ratio and progressive ratio (PR) self-administration
      tests. The results showed that JHW 007 attenuated METH-induced locomotor
      stimulation in a dose-dependent manner and had no stimulant effects when
      administered alone. The BZT analog, given as a pre-treatment, attenuated METH
      self-administration without affecting responding for sucrose. In the PR tests JHW
      007 produced an increase of the breaking point achieved for both METH- and
      sucrose self-administration, suggesting that the ability of the BZT analog to
      reduce self-administration may be linked to its ability to enhance the
      reinforcing properties of METH. Taken together, these data suggest that DAT
      inhibition with a high affinity blocker such as JHW 007 can exert differential
      effects on METH-associated behaviors, reducing METH-induced motor stimulation but
      augmenting METH's reinforcing effects.

PMID- 24675150
TI  - The role of endothelium-derived hyperpolarizing factor and cyclooxygenase
      pathways in the inhibitory serotonergic response to the pressor effect elicited
      by sympathetic stimulation in chronic sarpogrelate treated rats.
AB  - We have demonstrated that the antagonism of 5-HT2 receptors produces an
      enhancement of serotonergic sympathoinhibitory effect by 5-HT1D and 5-HT7
      activation. The aim of this work was to determine mechanisms involved in the 5
      hydroxytriptaminergic inhibitory action on the pressor responses elicited by
      sympathostimulation in pithed rats treated with a 5-HT2 receptor blocker. The
      blockade of 5-HT2 receptors was induced by orally sarpogrelate treatment (30
      mg/kg/day). Two weeks later, animals were anaesthetized and pithed. A bolus
      injection of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 ug/kg), a
      guanylyl cyclase inhibitor, or indomethacin (2mg/kg), a non-selective COX
      inhibitor, prior to the infusion of (2S)(+)-5-(1,3,5-trimethylpyrazol-4-yl)-2
      (dimethylamino)tetralin, AS-19 (5 ug/kg/min) were not able to abolish its
      inhibitory action. However, i.v. administration of glibenclamide (20mg/kg), a
      blocker of ATP-sensitive K(+) channels, completely reversed AS-19
      sympathoinhibitory action. The inhibitory effect of 2-[5-[3-(4
      methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine, L
      694,247 (5 ug/kg/min) was abolished by indomethacin, whereas pretreatment with
      ODQ had no effect. Nimesulide (3mg/kg), a COX-2 inhibitor, completely reversed
      the inhibitory action of L-694,247, whereas 1-[[4,5-bis (4-methoxyphenyl)-2
      thiazolyl]carbonyl]-4-methylpiperazine hydrochloride (FR122047) (3mg/kg), a COX-1
      inhibitor, partially blocked this action. The sympathoinhibition by 5-HT (20
      ug/kg/min) could not be elicited after i.v. treatment with indomethacin plus
      glibenclamide. In conclusion, these results suggest that in chronic sarpogrelate
      treated rats, the inhibitory serotonergic effect of the pressor responses induced
      by electrical stimulation of the sympathetic outflow via 5-HT7 and 5-HT1D
      receptor activation is mediated by KATP channel-mediated smooth muscle
      hyperpolarization and the COX pathway, respectively.

PMID- 24675151
TI  - Cryosclerosis. A forgotten endovenous procedure for treating the incompetence of
      the great saphenous vein. Short term results.
AB  - AIM: The aim of the present study was to prove the effectiveness, reliability and
      minimal invasiveness of cryosclerosis. METHODS: A prospective non-randomized
      study had been performed. The study enrolled 96 patients; 48 patients were
      treated by cryosclerosis and the other 48 by conventional stripping. Every time
      high ligation and phlebectomy of varices were done, in 1 patient the
      incompentence of the small saphenous vein was treated also by cryosclerosis.
      During the follow-up visits the obliteration of the great saphenous saphenous
      vein (GSV) was investigated; as primary objective of the study, secondary outcome
      measures were the most frequent complications of the conventional surgery,
      postoperative pain and recovery. Color-Duplex scan of the operated lower
      extremity was performed into 30 patients of the study group. Additionally, the
      vein wall (unhandled and frozen) was analyzed by transmission electron microscope
      in one case. All of the involved patients were examined at a follow-up visit (7
      days after surgery) and sent back a questionnaire (6-8 weeks after surgery).
      RESULTS: Recanalization was observed only in 2 patients (success rate after 6
      weeks: 93.3%). Thromboembolic events occurred only in the control group (1
      patient, minor pulmonary embolism). Regarding mild wound healing disorder and
      lymphorrhea there were no significant differences between the groups. Concerning
      postoperative pain, bruising and recovery the cryosclerosis was found
      significantly favorable. The incidence of limb swelling after surgery was the
      same in each group. Temporary sensory abnormalities seem to be frequent in the
      study group, but the results show that the rate of permanent saphenous nerve
      injury is higher in the patients operated with the conventional method. The
      histological examination showed changes in the frozen vein wall. CONCLUSION:
      Lacking long-term results, we can only consider that cryosclerosis allows the
      occlusion of the great saphenous vein, is minimal invasive and should be
      considered among endovenous procedures for treating GSV incompetence.

PMID- 24675152
TI  - Automation and validation of micronucleus detection in the 3D EpiDermTM human
      reconstructed skin assay and correlation with 2D dose responses.
AB  - Recent restrictions on the testing of cosmetic ingredients in animals have
      resulted in the need to test the genotoxic potential of chemicals exclusively in
      vitro prior to licensing. However, as current in vitro tests produce some
      misleading positive results, sole reliance on such tests could prevent some
      chemicals with safe or beneficial exposure levels from being marketed. The 3D
      human reconstructed skin micronucleus (RSMN) assay is a promising new in vitro
      approach designed to assess genotoxicity of dermally applied compounds. The assay
      utilises a highly differentiated in vitro model of the human epidermis. For the
      first time, we have applied automated micronucleus detection to this assay using
      MetaSystems Metafer Slide Scanning Platform (Metafer), demonstrating concordance
      with manual scoring. The RSMN assay's fixation protocol was found to be
      compatible with the Metafer, providing a considerably shorter alternative to the
      recommended Metafer protocol. Lowest observed genotoxic effect levels (LOGELs)
      were observed for mitomycin-C at 4.8 ug/ml and methyl methanesulfonate (MMS) at
      1750 ug/ml when applied topically to the skin surface. In-medium dosing with MMS
      produced a LOGEL of 20 ug/ml, which was very similar to the topical LOGEL when
      considering the total mass of MMS added. Comparisons between 3D medium and 2D
      LOGELs resulted in a 7-fold difference in total mass of MMS applied to each
      system, suggesting a protective function of the 3D microarchitecture.
      Interestingly, hydrogen peroxide (H2O2), a positive clastogen in 2D systems,
      tested negative in this assay. A non-genotoxic carcinogen, methyl carbamate,
      produced negative results, as expected. We also demonstrated expression of the
      DNA repair protein N-methylpurine-DNA glycosylase in EpiDermTM. Our preliminary
      validation here demonstrates that the RSMN assay may be a valuable follow-up to
      the current in vitro test battery, and together with its automation, could
      contribute to minimising unnecessary in vivo tests by reducing in vitro
      misleading positives. 

PMID- 24675153
TI  - Adoption into clinical practice of two therapies to manage swallowing disorders:
      exercise-based swallowing rehabilitation and electrical stimulation.
AB  - PURPOSE OF REVIEW: To review recent literature depicting a shift in dysphagia
      rehabilitation in adults. Distinguishing rehabilitation from compensation in
      dysphagia management, a review of basic exercise principles is followed by
      description of recent publications depicting exercise-based therapies.
      Subsequently, transcutaneous electrical stimulation (TES) is reviewed as it may
      contribute to exercise-based dysphagia rehabilitation in adults. RECENT FINDINGS:
      Surveys have documented extensive variability in the clinical application of
      dysphagia therapy techniques. Despite this variability, two trends are emerging
      in dysphagia rehabilitation research: documentation of physiologic and functional
      changes within the swallowing mechanism subsequent to therapy; and prophylactic
      exercise-based therapies. In addition, extensive efforts have emerged describing
      the potential application of TES in dysphagia rehabilitation. Though results of
      these efforts are conflicted, TES may serve a useful role as an adjunct to well
      developed exercise-based rehabilitation for dysphagia. SUMMARY: The focus of
      dysphagia rehabilitation in adults is changing. Current efforts indicate that
      exercise-based therapies should incorporate multiple principles of exercise
      physiology and document physiologic change within the impaired swallowing
      mechanism. TES may function as an adjunctive modality; however, current practices
      should be evaluated to develop additional parameters of stimulation that are
      focused toward specific dysphagia impairments.

PMID- 24675154
TI  - Advances in subcutaneous immunotherapy.
AB  - PURPOSE OF REVIEW: Current limitations in subcutaneous immunotherapy (SCIT)
      include the length of time required to achieve tolerance as well as the potential
      for systemic side-effects. Advances in allergen immunotherapy include targeted
      therapies to B-cell and T-cell pathways that can lead to more rapid
      desensitization and potentially the prevention of allergic disease. RECENT
      FINDINGS: Novel molecularly engineered compounds and delivery vehicles allow for
      rapid and efficient desensitization. Combination with immune modifiers, treatment
      with epitope-based compounds, and hypoallergenic recombinant vaccines have the
      potential to improve immunogenicity while limiting systemic side-effects.
      SUMMARY: Advances in SCIT create new therapeutic opportunities for patients to
      improve safety, efficacy, and compliance. Concepts using epitope-based
      immunotherapy and carrier-fusion peptides have the potential to induce tolerance
      quickly via selective B-cell and T-cell pathways.

PMID- 24675155
TI  - Transculturalization and validation of a Spanish translation of the specific
      lower limb osteoarthritis and quality of life questionnaire AMICAL: Arthrose des
      Membres Inferieurs et Qualite de vie AMIQUAL.
AB  - INTRODUCTION: Several generic questionnaires have been used to measure quality of
      life in patients with Osteoarthritis (OA) since few instruments have been
      developed specifically for OA and none was developed for Spanish speaking
      patients. The purpose of the study was to validate and adapt to Spanish the
      French questionnaire AMICAL to measure quality of life in patients with hip and
      knee OA. METHODS: Transversal, analytical study. The validation process was
      performed in phases: translation from French to Spanish, translated version
      analysis by a multidisciplinary expert team, application of a pilot test to
      patients to evaluate grammatical and content equivalence, blind back translation,
      and analysis. The questionnaire was applied to hip and knee OA patients, together
      with the SF-36 questionnaire, as well as the WOMAC and the Lequesne indexes. The
      reproducibility was evaluated applying the questionnaire after 72hours. The
      clinimetric analysis was calculated with SPSS 16.0. RESULTS: One hundred patients
      with hip OA and 100 patients with knee OA, radiological stages ii-iii, were
      included to evaluate homogeneity. Sixty-five patients with hip OA and 65 patients
      with knee OA were included to evaluate consistency. The final sample included 100
      hip and 100 patients knee OA patients to estimate homogeneities and 65 patients
      were evaluated to estimate consistency. Mean (SD) age of patients with hip and
      knee OA, was 56.34 +/- 13 and 60.1 +/- 9.2, respectively. Sixty seven percent and
      79.8% were female, respectively. Cronbach' alpha for AMICAL was 0.946 and 0.999,
      for hip OA and knee OA, respectively; and test-retest reliability using the
      intraclass correlation coefficients was 0.979 and 0.998, respectively. There was
      also a significant correlation with all the instruments (P<.05), except with the
      Lequesne index (r-0.383). CONCLUSIONS: The Spanish version of AMICAL
      questionnaire keep the clinimetric properties, homogeneity, and consistency, and
      has a good correlation with other instruments. Consequently, it is reliable, self
      applicable, and includes domains beyond the functional capacity that better
      evaluate the quality of life.

PMID- 24675156
TI  - A behavioural test battery to investigate tic-like symptoms, stereotypies,
      attentional capabilities, and spontaneous locomotion in different mouse strains.
AB  - The preclinical study of human disorders associated with comorbidities and for
      which the aetiology is still unclear may substantially benefit from multi-strain
      studies conducted in mice. The latter can help isolating experimental populations
      (strains) exhibiting distinct facets in the parameters isomorphic to the symptoms
      of a given disorder. Through a reverse-translation approach, multi-strain studies
      can inform both natural predisposing factors and environmental modulators. Thus,
      mouse strains selected for a particular trait may be leveraged to generate
      hypothesis-driven studies aimed at clarifying the potential role played by the
      environment in modulating the exhibition of the symptoms of interest. Tourette's
      syndrome (TS) constitutes a paradigmatic example whereby: it is characterized by
      a core symptom (tics) often associated with comorbidities (attention-deficit
      hyperactivity and obsessive-compulsive symptoms); it has a clear genetic origin
      though specific genes are, as yet, unidentified; its course (exacerbations and
      remissions) is under the influence of environmental factors. Based on these
      considerations, we tested four mouse strains (ABH, C57, CD1, and SJL) - varying
      along a plethora of behavioural, neurochemical, and immunological parameters - on
      a test battery tailored to address the following domains: tics (through the i.p.
      administration of the selective 5-HT2 receptor agonist DOI, 5mg/kg); locomotion
      (spontaneous locomotion in the home-cage); perseverative responding in an
      attentional set shifting task; and behavioural stereotypies in response to a
      single amphetamine (10mg/kg, i.p.) injection. Present data demonstrate that while
      ABH and SJL mice respectively exhibit selective increments in amphetamine-induced
      sniffing behaviour and DOI-induced tic-like behaviours, C57 and CD1 mice show a
      distinct phenotype, compared to other strains, in several parameters. 

PMID- 24675157
TI  - Role of the basolateral amygdala in retrieval of conditioned flavors in the awake
      rat.
AB  - Learned association between odor, taste and further post-ingestive consequence is
      known as flavor nutrient conditioned preference. Amygdala is supposed to be one
      of the areas involved in these associations. In the present study, one flavor was
      associated with a 16% glucose (CS(+)) whereas another flavor was paired with less
      reinforcing 4% glucose (CS(-)). We showed that CS(+) presentation after
      conditioning increased Fos expression in the basolateral nucleus of amygdala
      (BLA). Furthermore, we performed electrophysiological recordings in the BLA in
      free moving rats. After preference acquisition, rats were exposed to either the
      CS(+) or the CS(-). The proportion of neurons showing a decreased activity during
      the CS(-) presentation was significantly higher in conditioned rats compared to
      controls. Among this neuronal population recorded in conditioned rats, we noticed
      a significant proportion of neurons that also showed a decreased activity during
      the CS(+) presentation. Our data indicate an involvement of BLA during retrieval
      of learned flavors. It also suggests that both flavors might have acquired a
      biological value through conditioning. 

PMID- 24675158
TI  - Loss of motor coordination in an aging mouse model.
AB  - With age, there is an increase in motor deficits that leads to an increased
      incidence of slips and falls. As the elderly population continues to grow, there
      is a need for aging models and research that focus on behavioral deficits that
      occur with normal, non-diseased aging. The present study was designed to examine
      the appropriateness of C57Bl/6 male mice as aging animal models using the
      challenging beam and cylinder tests to measure motor coordination and spontaneous
      activity, respectively. Using young (2-4 mo), middle-aged (10-12 mo), and aged
      (22-24 mo) mice, we observed that aged C57Bl/6 male mice make more errors on the
      challenging beam task and take fewer hind limb steps as compared to young and
      middle-aged mice. Body weight and food intake were also measured to determine if
      these parameters were confounding factors in the interpretation of the behavioral
      data. Increases in body weight and food consumption were not observed in the
      oldest group that made the most errors. Together these data indicate that aged
      C57BL/6 mice display age-related motor deficits similar to those seen in humans
      and are an appropriate model of motor deficits that occur with age. 

PMID- 24675159
TI  - Involvement of the human medial temporal lobe in a visual discrimination task.
AB  - Recent imaging and lesion studies suggest that the human medial temporal lobe
      (including the hippocampus and the perirhinal cortex), which is traditionally
      believed to be of central importance for memory processing, is also involved in
      processing and discrimination of complex visual stimuli. The aim of this study
      was to use functional magnetic resonance imaging in healthy subjects to further
      elucidate the contributions of different medial temporal lobe structures to
      perceptual and mnemonic processing of faces and scenes, by directly comparing the
      activation in a visual discrimination and a recognition task (one week after
      encoding). A within-subjects full factorial analysis revealed significant
      hippocampal activation for both discrimination and recognition task, with no
      differential activations for the processing of faces or scenes. No perirhinal
      activation was found in either of the experimental conditions. These results
      support a perceptual-mnemonic theory of the medial temporal lobe, while
      questioning a simple mapping of different functions to single structures like
      hippocampus and perirhinal cortex. 

PMID- 24675160
TI  - Valproic acid effects in the hippocampus and prefrontal cortex in an animal model
      of post-traumatic stress disorder.
AB  - Reactive oxygen species (ROS) and pro-inflammatory cytokines (PIC) are
      upregulated in post-traumatic stress disorder (PTSD). Histone deacetylase
      inhibitors (HDACi) modify genetic transcription and can diminish ROS and PIC
      escalation. They can also modulate levels of neurotransmitters such as
      catecholamines and serotonin (5-HT). Thus, this study sought to analyze the
      effects of the HDACi valproic acid (VA) on oxidative stress, inflammation, and
      neurotransmitter modulation via a predator exposure/psychosocial stress animal
      model of PTSD. PTSD-like effects were induced in male Sprague-Dawley rats
      (n=6/group*4 groups). The rats were secured in Plexiglas cylinders and placed in
      a cage with a cat for 1h on days 1, 11, and 40 of a 40-day stress regimen. PTSD
      rats were also subjected to psychosocial stress via daily cage cohort changes. At
      the conclusion of the stress regimen, the treatment group (PTSD+VA) and control
      group (Control+VA) rats were given VA in their drinking water for 30 days. The
      rats were then euthanized and their brains were dissected to remove the
      hippocampus and prefrontal cortex (PFC). Whole blood was collected to assess
      systemic oxidative stress. ROS and PIC mRNA and protein elevation in the PTSD
      group were normalized with VA. Anxiety decreased in this group via improved
      performance on the elevated plus-maze (EPM). No changes were attributed to VA in
      the control group, and no improvements were noted in the vehicle groups. Results
      indicate VA can attenuate oxidative stress and inflammation, enhance fear
      extinction, and correct neurotransmitter aberrancies in a rat model of PTSD.

PMID- 24675161
TI  - Remote effects on the striatal dopamine system after fluid percussion injury.
AB  - PURPOSE: To investigate the effects of traumatic brain injury (TBI) on the
      dopamine system in the brain at different distances from the impaction site, we
      compared the release, reuptake, metabolism, and release probability of dopamine
      on the sides of the brain ipsilateral and contralateral to the injury at
      different time points after varying severities of fluid percussion injuries.
      MATERIALS AND METHODS: Tonic (1-pulse evoked) and bursting (10-pulse evoked)
      dopamine release changes in the ipsilateral and contralateral sides of the
      striatum resulting from mild (2-Pa) and severe (6-Pa) levels of fluid percussion
      injury were analyzed at the acute (2h and 24h), subacute (1 and 2 weeks), and
      chronic stages (4, 6, and 8 weeks) after injury by using fast scan cyclic
      voltammetry to measure brain slices. The metabolic rate of striatal dopamine was
      surveyed using high-performance liquid chromatography. The microglia reaction was
      analyzed using immunohistochemistry at each stage. RESULTS: In 6-Pa injured
      animals, for both tonic and bursting dopamine release, reuptake and release
      probability were suppressed on both the ipsilateral and contralateral sides of
      the striatum from the acute to the chronic stage. These neuronal activities were
      also affected at the subacute stage on both sides of the striatum in 2-Pa injured
      animals. The turnover rate of dopamine was not affected in the 2-Pa injured
      animals but increased gradually during the chronic stage in the 6-Pa injured
      group. CONCLUSION: TBI suppresses dopamine release and reuptake and affects the
      metabolic rate and release probability of dopamine on the sides of the
      nigrostriatal system both ipsilateral and contralateral to the injury during both
      the acute and subacute stages after the injury.

PMID- 24675163
TI  - Increased calcium/calmodulin-dependent protein kinase II activity by morphine
      sensitization in rat hippocampus.
AB  - Repeated exposure to drugs of abuse, such as morphine, elicits a progressive
      enhancement of drug-induced behavioral responses, a phenomenon termed behavioral
      sensitization. These changes in behavior may reflect long-lasting changes in some
      of the important molecules involved in memory processing such as
      calcium/calmodulin-dependent protein kinase II (CaMKII). In the present study, we
      investigated the effect of morphine sensitization on mRNA expression of alpha and
      beta isoforms and activity of CaMKII in the hippocampus of male rats. Animals
      were treated for 3 days with saline or morphine (20mg/kg) and following a washout
      period of 5 days, a challenge dose of morphine (5mg/kg) were administered. The
      results indicate that morphine administration in pre-treated animals produces
      behavioral sensitization, as determined by significant increase in locomotion and
      oral stereotypy behavior. In addition, repeated morphine treatment increased mRNA
      expression of both alpha and beta isoforms of CaMKII in the hippocampus. The
      present study also showed that induction of morphine sensitization significantly
      increased both Ca2+/calmodulin-independent and Ca2+/calmodulin-dependent
      activities of CaMK II in the rat hippocampus. However, acute administration of
      morphine (5mg/kg) did not alter either alpha and beta CaMKII mRNA expression or
      CaMKII activity in the hippocampus. The stimulation effects of morphine
      sensitization on mRNA expression and activity of CaMKII were completely abolished
      by administration of naloxone, 30min prior to s.c. injections of morphine
      (20mg/kg/day*3 days). Our data demonstrated that induction of morphine
      sensitization could effectively modulate the activity and the mRNA expression of
      CaMKII in the hippocampus and this effect of morphine was exerted by the
      activation of opioid receptors. 

PMID- 24675162
TI  - Dietary choline supplementation to dams during pregnancy and lactation mitigates
      the effects of in utero stress exposure on adult anxiety-related behaviors.
AB  - Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such
      as depression, anxiety, and schizophrenia. Maternal stress exposure is associated
      with these same illnesses in adult offspring, yet the relationship between
      prenatal stress and brain cholinergic function is largely unexplored. Thus, using
      a rodent model, the current study implemented an intervention aimed at buffering
      the potential effects of prenatal stress on the developing brain cholinergic
      system. Specifically, control and stressed dams were fed choline-supplemented or
      control chow during pregnancy and lactation, and the anxiety-related behaviors of
      adult offspring were assessed in the open field, elevated zero maze and social
      interaction tests. In the open field test, choline supplementation significantly
      increased center investigation in both stressed and nonstressed female offspring,
      suggesting that choline-supplementation decreases female anxiety-related behavior
      irrespective of prenatal stress exposure. In the elevated zero maze, prenatal
      stress increased anxiety-related behaviors of female offspring fed a control diet
      (normal choline levels). However, prenatal stress failed to increase anxiety
      related behaviors in female offspring receiving supplemental choline during
      gestation and lactation, suggesting that dietary choline supplementation
      ameliorated the effects of prenatal stress on anxiety-related behaviors. For male
      rats, neither prenatal stress nor diet impacted anxiety-related behaviors in the
      open field or elevated zero maze. In contrast, perinatal choline supplementation
      mitigated prenatal stress-induced social behavioral deficits in males, whereas
      neither prenatal stress nor choline supplementation influenced female social
      behaviors. Taken together, these data suggest that perinatal choline
      supplementation ameliorates the sex-specific effects of prenatal stress. 

PMID- 24675164
TI  - Tempofilter II implantation in patients with lower extremity fractures and
      proximal deep vein thrombosis.
AB  - PURPOSE: We aimed to examine the efficacy and safety of Tempofilter II (B. Braun,
      Melsungen, Germany) implantation to prevent pulmonary embolism in patients with
      lower-extremity fractures and proximal deep vein thrombosis (DVT). MATERIALS AND
      METHODS: The records of patients with lower limb fractures and proximal DVT who
      were implanted with Tempofilter II devices from May 2004 to August 2009 were
      reviewed. Data collected included success rate, occurrence of pulmonary embolism,
      retrieval rate, and complications. RESULTS: A total of 176 eligible patients,
      including 129 males (73.3%) and 47 females (26.7%) with a median age of 42.0
      years (interquartile range [IQR], 34.0-52.0 years) were included in the study.
      Filters were successfully implanted in 174 patients (98.9%). One patient
      experienced a pulmonary embolism after implantation and died. Filters were
      removed without complications in all other patients. Median filter implantation
      time was 27 days (IQR, 25.0-29.0 days). Visible organized thrombi were present on
      the surface of 144 (82.8%) of filters after removal, and the diameter of most
      thrombi (n=124) ranged from 0.5 to 1.0 cm. Filters migrated <2 cm in 104 patients
      (59.8%) and >= 2 cm in five patients (2.9%). In these five cases, three filters
      migrated into the right atrium and two migrated to the orifice of the renal
      veins. CONCLUSION: Tempofilter II is safe and may be useful in cases of lower
      extremity fracture with proximal DVT for the prevention of pulmonary embolism.
      The filter is easily placed and retrieved, and associated with minimal
      complications.

PMID- 24675166
TI  - Clinical value of prostate segmentation and volume determination on MRI in benign
      prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of
      the prostate, which occurs primarily in the transitional zone. BPH is highly
      prevalent and is a major cause of lower urinary tract symptoms in aging males,
      although there is no direct relationship between prostate volume and symptom
      severity. The progression of BPH can be quantified by measuring the volumes of
      the whole prostate and its zones, based on image segmentation on magnetic
      resonance imaging. Prostate volume determination via segmentation is a useful
      measure for patients undergoing therapy for BPH. However, prostate segmentation
      is not widely used due to the excessive time required for even experts to
      manually map the margins of the prostate. Here, we review and compare new methods
      of prostate volume segmentation using both manual and automated methods,
      including the ellipsoid formula, manual planimetry, and semiautomated and fully
      automated segmentation approaches. We highlight the utility of prostate
      segmentation in the clinical context of assessing BPH. 

PMID- 24675167
TI  - Tweaking the magnetism of MoS2 nanoribbon with hydrogen and carbon passivation.
AB  - Using density functional theory (DFT), we report the modulated electronic and
      magnetic properties of MoS2 nanoribbon by passivating the ribbon edges with H and
      C separately. For the modeled symmetric MoS2 nanoribbon with a zig-zag type edge,
      one side is terminated at Mo and the other side is terminated at S. For the zig
      zag type, we have studied two ribbons of width ~3 A and 6 A respectively. Both of
      these pristine zig-zag type nanoribbons are found to be metallic and also
      ferromagnetic. However, the increase in the ribbon width results in a decrease in
      the net magnetic moment of the nanoribbon. Thereafter, we study the modulated
      electronic and magnetic properties of the nanoribbon of ~3 A width by saturating
      the ribbon edges with H and C. In one case, by passivating the zig-zag type
      ribbon with H at the S terminated edge, we find a net increase in magnetic moment
      of the ribbon when compared with the pristine one. Furthermore, when the ribbon
      is passivated with H at both of the edges, the net magnetic moment shows a
      decreasing trend. In another case, the zig-zag nanoribbon is passivated with C in
      a similar fashion to H and we find with one edge passivation the net magnetic
      moment of the ribbon decreases, whereas with both edges C passivated the ribbon
      magnetism increases significantly. However, the nanoribbon modeled with the
      armchair type of edge and terminated with Mo at both sides is found to be non
      magnetic and semiconducting. Passivating the armchair type nanoribbon with H and
      C, we find the band gap shows an increasing trend when going from one side to
      both sides passivation. In all cases, the armchair type nanoribbons show non
      magnetic behavior.

PMID- 24675165
TI  - Angioplasty for pediatric renovascular hypertension: a 13-year experience.
AB  - PURPOSE: We aimed to evaluate the long-term outcome and efficacy of percutaneous
      transluminal renal angioplasty (PTRA) for pediatric renal artery stenosis (RAS),
      which is an important cause of medication-refractory pediatric hypertension.
      MATERIALS AND METHODS: We retrospectively evaluated 22 hypertensive children (age
      range, 3-17 years) who underwent PTRA from February 2000 to July 2012. Sixteen
      patients had Takayasu arteritis and six fibromuscular dysplasia. Five were not
      included in the statistical analysis due to loss to follow-up. RESULTS: Technical
      success was achieved in 32 of 34 procedures (94.1%). The stenosis rate decreased
      from 84.5% before PTRA to 20.1% after PTRA. Treatment was effective in 72.7%
      (16/22) of patients, including complete cure in 27.3% (6/22) and improvement in
      45.5% (10/22). Systolic and diastolic blood pressures decreased from 153 +/- 19.1
      to 131.7 +/- 21.4 mmHg and from 97.9 +/- 14.2 to 83.6 +/- 19.3 mmHg, respectively
      (P <0.01). Number of antihypertensive agents decreased from 2.7 to 0.5 per
      patient. Restenosis was detected in 40.9% (9/22) of patients, with a restenotic
      interval of 11.8 months (range, 3-47 months). Lesion length was strongly
      correlated with clinical success (cure and improvement) (independent-sample t
      test, P <0.001; binary logistic regression, P = 0.040). CONCLUSION: Lesion length
      is an important determination of clinical success with PTRA for pediatric RAS.
      PTRA is an appropriate treatment option for pediatric renovascular hypertension
      due to Takayasu arteritis and fibromuscular dysplasia.

PMID- 24675169
TI  - Diverse roles of the GlcP glucose permease in free-living and symbiotic
      cyanobacteria.
AB  - Certain cyanobacteria can form symbiotic associations with plants, where the
      symbiont supplies the plant partner with nitrogen and in return obtains sugars.
      We recently showed that in the symbiotic cyanobacterium Nostoc punctiforme, a
      glucose specific permease, GlcP, is necessary for the symbiosis to be formed.
      Results presented here from growth yield measurements of mutant strains with
      inactivated or overexpressing sugar transporters suggest that GlcP could be
      induced by a symbiosis specific substance. We also discuss that the transporter
      may have a role other than nutritional once the symbiosis is established, i.e.,
      during infection, and more specifically in the chemotaxis of the symbiont.
      Phylogenetic analysis shows that the distribution of GlcP among cyanobacteria is
      likely influenced by horizontal gene transfer, but also that it is not correlated
      with symbiotic competence. Instead, regulatory patterns of the transporter in
      Nostoc punctiforme likely constitute symbiosis specific adaptations.

PMID- 24675168
TI  - Dietary omega-6 fatty acid lowering increases bioavailability of omega-3
      polyunsaturated fatty acids in human plasma lipid pools.
AB  - BACKGROUND: Dietary linoleic acid (LA, 18:2n-6) lowering in rats reduces n-6
      polyunsaturated fatty acid (PUFA) plasma concentrations and increases n-3 PUFA
      (eicosapentaenoic (EPA) and docosahexaenoic acid (DHA)) concentrations.
      OBJECTIVE: To evaluate the extent to which 12 weeks of dietary n-6 PUFA lowering,
      with or without increased dietary n-3 PUFAs, alters unesterified and esterified
      plasma n-6 and n-3 PUFA concentrations in subjects with chronic headache. DESIGN:
      Secondary analysis of a randomized trial. Subjects with chronic headache were
      randomized for 12 weeks to (1) average n-3, low n-6 (L6) diet; or (2) high n-3,
      low n-6 LA (H3-L6) diet. Esterified and unesterified plasma fatty acids were
      quantified at baseline (0 weeks) and after 12 weeks on a diet. RESULTS: Compared
      to baseline, the L6 diet reduced esterified plasma LA and increased esterified n
      3 PUFA concentrations (nmol/ml), but did not significantly change plasma
      arachidonic acid (AA, 20:4n-6) concentration. In addition, unesterified EPA
      concentration was increased significantly among unesterified fatty acids. The H3
      L6 diet decreased esterified LA and AA concentrations, and produced more marked
      increases in esterified and unesterified n-3 PUFA concentrations. CONCLUSION:
      Dietary n-6 PUFA lowering for 12 weeks significantly reduces LA and increases n-3
      PUFA concentrations in plasma, without altering plasma AA concentration. A
      concurrent increase in dietary n-3 PUFAs for 12 weeks further increases n-3 PUFA
      plasma concentrations and reduces AA.

PMID- 24675170
TI  - Bacterial-like PPP protein phosphatases: novel sequence alterations in pathogenic
      eukaryotes and peculiar features of bacterial sequence similarity.
AB  - Reversible phosphorylation is a widespread modification affecting the great
      majority of eukaryotic cellular proteins, and whose effects influence nearly
      every cellular function. Protein phosphatases are increasingly recognized as
      exquisitely regulated contributors to these changes. The PPP (phosphoprotein
      phosphatase) family comprises enzymes, which catalyze dephosphorylation at serine
      and threonine residues. Nearly a decade ago, "bacterial-like" enzymes were
      recognized with similarity to proteins from various bacterial sources: SLPs
      (Shewanella-like phosphatases), RLPHs (Rhizobiales-like phosphatases), and ALPHs
      (ApaH-like phosphatases). A recent article from our laboratory appearing in Plant
      Physiology characterizes their extensive organismal distribution, abundance in
      plant species, predicted subcellular localization, motif organization, and
      sequence evolution. One salient observation is the distinct evolutionary
      trajectory followed by SLP genes and proteins in photosynthetic eukaryotes vs.
      animal and plant pathogens derived from photosynthetic ancestors. We present here
      a closer look at sequence data that emphasizes the distinctiveness of pathogen
      SLP proteins and that suggests that they might represent novel drug targets. A
      second observation in our original report was the high degree of similarity
      between the bacterial-like PPPs of eukaryotes and closely related proteins of the
      "eukaryotic-like" phyla Myxococcales and Planctomycetes. We here reflect on the
      possible implications of these observations and their importance for future
      research. 

PMID- 24675171
TI  - Overexpression of a pectin methylesterase inhibitor in Arabidopsis thaliana leads
      to altered growth morphology of the stem and defective organ separation.
AB  - The methylesterification status of cell wall pectins, mediated through the
      interplay of pectin methylesterases (PMEs) and pectin methylesterase inhibitors
      (PMEIs), influences the biophysical properties of plant cell walls. We found that
      the overexpression of a PMEI gene in Arabidopsis thaliana plants caused the stems
      to develop twists and loops, most strongly around points on the stem where leaves
      or inflorescences failed to separate from the main stem. Altered elasticity of
      the stem, underdevelopment of the leaf cuticle, and changes in the sugar
      composition of the cell walls of stems were evident in the PMEI overexpression
      lines. We discuss the mechanisms that potentially underlie the aberrant growth
      phenotypes.

PMID- 24675172
TI  - The rice F-box protein KISS ME DEADLY2 functions as a negative regulator of
      cytokinin signalling.
AB  - Cytokinins are plant hormones that play critical roles in growth and development.
      We recently determined that the transcriptional response to cytokinin of
      Arabidopsis is modulated by the KISS ME DEADLY (KMD) family of F-box proteins.
      Here we demonstrate a conserved function for a member of the rice KMD family.
      Ectopic overexpression of OsKMD2 in Arabidopsis results in decreased cytokinin
      sensitivity based on a hypocotyl growth response assay, the decrease in
      sensitivity correlating with a decrease in the levels of the transcriptional
      regulator AtARR12. Furthermore, OsKMD2 directly interacts with AtARR12 based on
      yeast two-hybrid and co-immunoprecipitation assays. These results indicate that
      both monocots and dicots employ a similar KMD-dependent mechanism to regulate the
      transcriptional response to cytokinin.

PMID- 24675173
TI  - The crystallization process of liquid vanadium studied by ab initio molecular
      dynamics.
AB  - We present a study of the crystallization process in liquid vanadium over a
      temperature range from 3000 K down to 1500 K using ab initio molecular dynamics
      simulations. Short-range order evolution during solidification is studied using
      various structural analysis methods. We show that the icosahedral-like short
      range order is detected in the stable liquid phase and grows upon supercooling.
      The system undergoes a first-order phase transition (from a liquid to a solid
      state) at a temperature of about 1600 K. The crystal nucleation process is
      further studied using the time-temperature transformation mechanism by annealing
      the system at 1650 K. The nucleation is examined using bond-orientational order
      and density fluctuation analysis. Our finding is that various precursors appear
      in the region of high bond-orientational order with the majority having body
      centered cubic (bcc)-like symmetry. This bcc-like region grows on annealing via
      thermal fluctuations. Our results reveal that the bond-orientational order
      precedes the density fluctuation, and is the main driving factor for nucleation. 

PMID- 24675174
TI  - Estimating the effective density of engineered nanomaterials for in vitro
      dosimetry.
AB  - The need for accurate in vitro dosimetry remains a major obstacle to the
      development of cost-effective toxicological screening methods for engineered
      nanomaterials. An important key to accurate in vitro dosimetry is the
      characterization of sedimentation and diffusion rates of nanoparticles suspended
      in culture media, which largely depend upon the effective density and diameter of
      formed agglomerates in suspension. Here we present a rapid and inexpensive method
      for accurately measuring the effective density of nano-agglomerates in
      suspension. This novel method is based on the volume of the pellet obtained by
      benchtop centrifugation of nanomaterial suspensions in a packed cell volume tube,
      and is validated against gold-standard analytical ultracentrifugation data. This
      simple and cost-effective method allows nanotoxicologists to correctly model
      nanoparticle transport, and thus attain accurate dosimetry in cell culture
      systems, which will greatly advance the development of reliable and efficient
      methods for toxicological testing and investigation of nano-bio interactions in
      vitro. 

PMID- 24675175
TI  - Synthesis of substituted pyrimidines as corticotropin releasing factor (CRF)
      receptor ligands.
AB  - Corticotropin releasing factor (CRF) is a neuropeptide hormone produced from the
      hypothalamus that controls the secretion of corticotropin (ACTH) from the
      anterior pituitary gland that, in turn, prompts the adrenal glands to secrete
      glucocorticoids. This involvement in the hypothalamic-pituitary-adrenal axis
      (HPA) in response to stress and also playing a key role in behavioral,
      cardiovascular, immune and gastrointestinal systems made CRF binding to its
      receptors an important target in drug discovery aiming to develop lead compounds
      with the potential to treat various stress-related disorders including
      depression, anxiety and addictive disorders. Several non-peptide CRF1 receptor
      antagonists were developed by pharmaceutical companies and are currently in
      clinical trials with the aim of improving the health consequences of chronic
      stress and for use in the clinical management of anxiety and stress. Many showed
      promising results not only in treatment of anxiety and depression but also in
      treatment of CRF-induced hypertension, as well as in treatment of arthritis,
      irritable bowel syndrome and peptic ulcers. In this manuscript, we describe the
      synthesis of substituted pyrimidines with close structural similarities to
      reported lead compounds with promising CRF1 receptor affinities and carrying
      groups known to be associated with optimum affinity to CRF1 receptors. The
      affinity of the newly prepared compounds in comparison to antalarmin, a potent
      CRF1 receptor antagonist in clinical trials as a standard, is also described.
      Four compounds from the new series showed promising CRF1 receptor affinity. 

PMID- 24675176
TI  - Solid-supported synthesis, molecular modeling, and biological activity of long
      chain arylpiperazine derivatives with cyclic amino acid amide fragments as 5
      HT(7) and 5-HT(1A) receptor ligands.
AB  - A 47-membered library of novel long-chain arylpiperazines, which contained cyclic
      amino acid amides in the terminal fragment (pyrrolidine-2-carboxamide and 1,2,3,4
      tetrahydroisoquinoline-3-carboxamide), was synthesized on Rink-amide resin and
      biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors.
      Surprisingly, members of the designed series containing piperidine-2-carboxamide
      fragments underwent hydrolysis, which occurred during the acidic treatment for
      release from the solid-support, to their respective pipecolic acid analogs.
      Representative compounds from the library displayed high-to-low affinity for 5
      HT7 (Ki = 18-3134 nM) and 5-HT1A (Ki = 0.5-6307 nM) sites. The possible
      interactions implicated in binding of the studied compounds to the 5-HT7 receptor
      were supported by molecular modeling. Research was also applied to support the
      exploration of the influence of the amide fragment, the length of alkylene
      spacer, and arylpiperazine substituents on the receptor's affinity and
      selectivity. 

PMID- 24675177
TI  - Synthesis and anticancer activities of 4-(4-substituted piperazin)-5,6,7
      trialkoxy quinazoline derivatives.
AB  - A series of 4-(4-substituted piperazin)-5,6,7-trialkoxy quinazoline was prepared
      by conventional heating methods. Among these compounds, the crystal structure of
      compound 10o (CCDC: 916922) was determined by X-ray crystallography. Bioassay
      results showed that most target compounds had certain inhibition activities
      against proliferation of tumor cells, and some compounds even had good broad
      spectrum inhibition activities. The ethoxyl series of compounds possessed higher
      inhibition activities against tumor cells than the methoxyl series of compounds.
      Bioactivity tests showed that the IC50 values of compound 10s against PC3,
      MGC803, A375, and A549 cells were 1.8, 2.8, 1.3, and 2.9 MUMU, respectively,
      which were much higher than those of commercial gefitinib (7.2, 7.6, 7.2, and 9.8
      MUM, respectively). Conversely, the IC50 values of compound 10s were very low
      against NH3T3, indicating only weak effect on normal cells as also proven by
      lactate dehydrogenase and acridine orange/ethidium bromide staining. Analyses of
      cell configuration and cell cycle revealed that compound 10s possibly caused
      cells to remain at G0/G1 phase by inhibiting cell proliferation for 24 h.
      Compound 10s also inhibited the phosphorylation of ERK1/2 and P38 with obvious
      concentration dependence. Thus, these compounds can inhibit the proliferation of
      A549 cells through the interruption of ERK1/2 and P38signaling pathways. 

PMID- 24675178
TI  - Discovery of 2-iminobenzimidazoles as potent hepatitis C virus inhibitors with a
      novel mechanism of action.
AB  - In this report we describe 2-iminobenzimidazole (IBI) analogs, identified during
      the course of a phenotypic high-throughput screening campaign, as novel hepatitis
      C virus (HCV) inhibitors. A series of IBI derivatives was synthesized and
      evaluated for their inhibitory activity against infectious HCV. Among the IBIs
      derivatives studied in this work, we identified promising compounds with high
      antiviral efficacy, high selectivity index and good microsomal stability.
      Noteworthy, the IBI series exhibited inhibitory activity on early and late steps
      of the viral cycle, but not in the HCV replicon system demonstrating a mechanism
      of action distinct from clinical-stage and approved anti-HCV drugs. Overall, our
      results suggest that IBIs are predestinated for further exploration as lead
      compounds for novel HCV interventions. 

PMID- 24675179
TI  - Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide
      derivatives as potent inhibitors of cholinesterases.
AB  - The present study reports the synthesis of cinnamide derivatives and their
      biological activity as inhibitors of both cholinesterases and anticancer agents.
      Controlled inhibition of brain acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) may slow neurodegeneration in Alzheimer's diseases
      (AD). The anticholinesterase activity of phenylcinnamide derivatives was
      determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum
      butyrylcholinesterase (hBChE) and some of the compounds appeared as moderately
      potent inhibitors of EeAChE and hBChE. The compound 3-(2-(Benzyloxy)phenyl)-N
      (3,4,5-trimethoxyphenyl)acrylamide (3i) showed maximum activity against EeAChE
      with an IC50 0.29 +/- 0.21 MUM whereas 3-(2-chloro-6-nitrophenyl)-N-(3,4,5
      trimethoxyphenyl)acrylamide (3k) was proved to be the most potent inhibitor of
      hBChE having IC50 1.18 +/- 1.31 MUM. To better understand the enzyme-inhibitor
      interaction of the most active compounds toward cholinesterases, molecular
      modelling studies were carried out on high-resolution crystallographic
      structures. The anticancer effects of synthesized compounds were also evaluated
      against cancer cell line (lung carcinoma). The compounds may be useful leads for
      the design of a new class of anticancer drugs for the treatment of cancer and
      cholinesterase inhibitors for Alzheimer's disease (AD).

PMID- 24675180
TI  - Conformation and recognition of DNA damaged by antitumor cis-dichlorido
      platinum(II) complex of CDK inhibitor bohemine.
AB  - A substitution of the ammine ligands of cisplatin, cis-[Pt(NH3)2Cl2], for cyclin
      dependent kinase (CDK) inhibitor bohemine (boh), [2-(3-hydroxypropylamino)-6
      benzylamino-9-isopropylpurine], results in a compound, cis-[Pt(boh)2Cl2] (C1),
      with the unique anticancer profile which may be associated with some features of
      the damaged DNA and/or its cellular processing (Travnicek Z et al. (2003) J Inorg
      Biochem94, 307-316; Liskova B (2012) Chem Res Toxicol25, 500-509). A combination
      of biochemical and molecular biology techniques was used to establish mechanistic
      differences between cisplatin and C1 with respect to the DNA damage they produce
      and their interactions with critical DNA-binding proteins, DNA-processing enzymes
      and glutathione. The results show that replacement of the NH3 groups in cisplatin
      by bohemine modulates some aspects of the mechanism of action of C1. More
      specifically, the results of the present work are consistent with the thesis
      that, in comparison with cisplatin, effects of other factors, such as: (i) slower
      rate of initial binding of C1 to DNA; (ii) the lower efficiency of C1 to form
      bifunctional adducts; (iii) the reduced bend of longitudinal DNA axis induced by
      the major 1,2-GG intrastrand cross-link of C1; (iv) the reduced affinity of HMG
      domain proteins to the major adduct of C1; (v) the enhanced efficiency of the DNA
      adducts of C1 to block DNA polymerization and to inhibit transcription activity
      of human RNA pol II and RNA transcription; (vi) slower rate of the reaction of C1
      with glutathione, may partially contribute to the unique activity of C1. 

PMID- 24675181
TI  - Proteomic identification of differentially expressed proteins during the
      acquisition of somatic embryogenesis in oil palm (Elaeis guineensis Jacq.).
AB  - In the present study we have identified and characterized the proteins expressed
      during different developmental stages of Elaeis guineensis calli obtained from
      zygotic embryos. We were interested in the possible proteomic changes that would
      occur during the acquisition of somatic embryogenesis and therefore samples were
      collected from zygotic embryos (E1), swollen explants 14days (E2) in induction
      medium, primary callus (E3), and pro-embryogenic callus (E4). The samples were
      grinded in liquid nitrogen, followed by total protein extraction using phenol and
      extraction buffer. Proteins were analyzed by two-dimensional electrophoresis (2
      DE) and the differentially expressed protein spots were analyzed by MALDI-TOF
      mass spectrometry (MS and MS/MS). Interestingly, we have identified proteins,
      which can be used as potential candidates for future studies aiming at the
      development of biomarkers for embryogenesis acquisition and for the different
      stages leading to pro-embryogenic callus formation such as type IIIa membrane
      protein cp-wap13, fructokinase and PR proteins. The results obtained shed some
      light on the biochemical events involved in the process of somatic embryogenesis
      of E. guineensis obtained from zygotic embryos. The use of stage-specific protein
      markers can help monitor cell differentiation and contribute to improve the
      protocols for successfully cloning the species. BIOLOGICAL SIGNIFICANCE:
      Understanding the fate and dynamics of cells and tissues during callus formation
      is essential to understand totipotency and the mechanisms involved during
      acquisition of somatic embryogenesis (SE). In this study we have investigated the
      early stages of somatic embryogenesis induction in oil palm and have identified
      potential markers as well as proteins potentially involved in embryogenic
      competence acquisition. The use of these proteins can help improve tissue culture
      protocols in order to increase regeneration rates. This article is part of a
      Special Issue entitled: Environmental and structural proteomics.

PMID- 24675182
TI  - Mechanism of Penicillium expansum in response to exogenous nitric oxide based on
      proteomics analysis.
AB  - Penicillium expansum is an important fungal pathogen, which causes blue mold rot
      in various fruits and produces a mycotoxin (patulin) with potential damage to
      public health. Here, we found that nitric oxide (NO) donor could significantly
      inhibit germinability of P. expansum spores, resulting in lower virulence to
      apple fruit. Based on two dimension electrophoresis (2-DE) and mass spectrometry
      (MS) analysis, we identified ten differentially expressed proteins in response to
      exogenous NO in P. expansum. Among of them, five proteins, such as glutamine
      synthetase (GS), amidohydrolase, nitrilases, nitric oxide dioxygenase (NOD) and
      heat shock protein 70, were up-regulated. Others including tetratricopeptide
      repeat domain, UDP-N-acetylglucosamine pyrophosphorylase, enolase (Eno), heat
      shock protein 60 and K homology RNA-binding domain were down-regulated. The
      expression of three genes associated with the identified proteins (GS, NOD, and
      Eno) was evaluated at the mRNA level by RT-PCR. Our results provide the novel
      evidence for understanding the mechanism, by which NO regulates growth of P.
      expansum and its virulence. BIOLOGICAL SIGNIFICANCE: Crop diseases caused by
      fungal pathogens lead to huge economic losses every year in the world.
      Application of chemical fungicides to control diseases brings the concern about
      food and environmental safety. Screening new antimicrobial compounds and
      exploring involved mechanisms have great significance to development of new
      disease management strategies. Nitric oxide (NO), as an important intracellular
      signaling molecule, has been proved to be involved in many physiological
      processes and defense responses during plant-pathogen interactions. In this
      study, we firstly found that NO at high concentration could distinctly delay
      spore germination and significantly reduce virulence of P. expansum to fruit
      host, identified some important proteins in response to NO stress and
      characterized the functions of these proteins. These results provide novel
      evidence for understanding the mechanism of NO regulating virulence of the fungal
      pathogen, but are beneficial for screening new targets of antifungal compounds.

PMID- 24675183
TI  - Using propensity score analysis to compare major complications between DIEP and
      free muscle-sparing TRAM flap breast reconstructions.
AB  - BACKGROUND: Previous studies comparing muscle-sparing transverse rectus abdominis
      myocutaneous (TRAM) versus deep inferior epigastric artery perforator (DIEP) free
      flaps have not considered procedure selection bias. Propensity score analysis
      provides a statistical approach to consider preoperative factors in flap
      selection, and was used to compare major complications (breast and abdominal)
      between these microsurgical breast reconstruction (free muscle-sparing TRAM
      versus DIEP). METHODS: This study evaluated major breast and abdominal
      complications in 292 consecutive patients (428 free abdominal flaps). Propensity
      scores were calculated for patient differences affecting flap selection (DIEP
      versus free muscle-sparing TRAM). Multivariate logistic models using selected
      covariates separately analyzed breast and abdominal complications between flap
      methods. RESULTS: There were 83 major complications (28 percent): breast, 20
      percent; abdomen, 8 percent. Using propensity scores, the adjusted odds of
      abdominal complications were significantly higher in free muscle-sparing TRAM
      than in DIEP flaps (OR, 2.73; 95 percent CI, 1.01 to 7.07). With prior
      chemotherapy, body mass index significantly increased abdominal complications
      (OR, 1.16; 95 percent CI, 1.01 to 1.34). Using propensity scores, there was no
      significant association between reconstruction method and breast complications;
      diabetics had significantly increased breast complications (OR, 4.19; 95 percent
      CI, 1.14 to 15.98). Previous abdominal operations (OR, 1.77; 95 percent CI, 0.96
      to 3.30) and immediate reconstruction (OR, 1.86; 95 percent CI, 0.94 to 3.71)
      approached significance. CONCLUSIONS: Propensity score analysis indicated
      significantly higher abdominal complications in free muscle-sparing TRAM compared
      with DIEP flaps. This study highlights the importance of separately evaluating
      recipient breast and donor abdominal complications and use of propensity scores
      to minimize procedure selection bias. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 24675184
TI  - Understanding the effect of breast augmentation on quality of life: prospective
      analysis using the BREAST-Q.
AB  - BACKGROUND: The aim of this study was to prospectively evaluate patient
      satisfaction and quality of life with elective breast augmentation. METHODS:
      Patients with bilateral submuscular breast augmentations prospectively completed
      the BREAST-Q preoperatively and 6 weeks and 6 months postoperatively; t tests
      compared preoperative and postoperative scores at 6 weeks and 6 months, and
      standard indicators of effect sizes were calculated. Logistic regression was used
      to evaluate the association between patient and surgical factors on satisfaction
      outcomes. RESULTS: The study sample included 611 female patients with the
      following characteristics: (1) mean age of 33.5 years; (2) mean body mass index
      of 21.7; (3) and mean implant volume of 360; with (4) 73 percent having received
      a silicone implant. Significant improvements were found in patient satisfaction
      with breasts (p < 0.001), psychosocial well-being (p < 0.001), and sexual well
      being (p < 0.001) at 6 weeks and 6 months postoperatively, and all were
      associated with a very large Kazis effect size of 3.66, 2.39, and 2.56 at 6
      months, respectively. However, at both 6 weeks and 6 months postoperatively,
      physical well-being remained significantly below preoperative baseline scores. In
      addition, satisfaction with breasts and with the overall surgical experience was
      significantly lower among older patients (p = 0.01 and 0.02, respectively).
      CONCLUSIONS: Breast augmentation is associated with high patient satisfaction and
      significant improvements in quality of life. However, physicians should inform
      patients that submuscular augmentations are associated with a delay in recovery
      of physical functioning and be aware that older patients may experience
      diminished satisfaction and should counsel accordingly. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 24675185
TI  - Aesthetic applications of Brava-assisted megavolume fat grafting to the breasts:
      a 9-year, 476-patient, multicenter experience.
AB  - BACKGROUND: Autologous fat grafting to the breasts was banned in 1987 because of
      unpredictable graft retention and cyst formation that could not be differentiated
      from cancer. Surgical and radiologic advances induced a lifting of the ban in
      2009. Small- to moderate-volume autologous fat grafting to the breast has become
      common. The authors present their aesthetic applications of megavolume autologous
      fat grafting to the breast. METHODS: Autologous fat grafting with Brava
      preexpansion was performed on 294 patients for aesthetic augmentation, 45
      patients for congenital deformity correction, 43 patients for iatrogenic
      deformity correction, and six patients for implant-to-fat conversion. Autologous
      fat grafting for implant-to-fat conversion was performed on 88 patients without
      Brava. A case example is presented for each indication. The baseline,
      perioperative, grafted, and postoperative volumes were recorded. RESULTS: Follow
      up ranges from 6 months to 9 years (mean, 3.5 years). The mean volume grafted was
      346 ml per breast, and the mean postoperative augmentation measured at least 6
      months postoperatively was 266 ml per breast. No patients required open biopsy or
      were diagnosed with cancer. There was one pneumothorax, requiring a temporary
      chest tube, with no further complication. CONCLUSION: Large-volume autologous fat
      grafting after Brava use or implant removal is a safe and effective alternative
      for breast augmentation and deformity correction. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24675187
TI  - A clinical scalable cryopreservation method of adipose tissue for reconstructive
      surgery assessed by stromal vascular fraction and mice studies.
AB  - BACKGROUND: Adipose tissue is widely used in plastic surgery. The main obstacle
      is that it can be used only immediately after liposuction, while reconstruction
      often requires several procedures to achieve optimal results. This study aimed to
      develop a cryopreservation protocol directly applicable to clinical situations,
      allowing repetitive procedures without multiple tissue harvests. METHODS: The
      authors first tested scalable bags suitable for therapeutic uses. All subsequent
      experiments were performed in those bags. The authors evaluated in vitro, on the
      basis of cell viability, cell number, phenotype, and stromal cell proliferation,
      the efficacy of six cryopreservation media composed of an external cryoprotectant
      (human albumin or hydroxylethyl starch) with or without an internal
      cryoprotectant (dimethyl sulfoxide). Two storage temperatures (-196 degrees C and
      -80 degrees C) were tested in vitro and in vivo (subcutaneous graft in 30 nude
      mice) with the selected medium. RESULTS: The combination of 5% dimethyl sulfoxide
      and 95% hydroxylethyl yielded in vitro results that were good and the most
      consistent. With this cryoprotective solution, the authors observed no
      significant difference in vitro for a storage period of 7 days. When the storage
      was extended to 1 month, the cell viability was decreased by 10 percent for both
      storage temperatures. The in vivo experiments assessed the superiority of
      cryopreservation at -80 degrees C with less graft resorption (60 percent and 70
      percent, respectively, for -80 degrees C and -196 degrees C) and less fibrosis.
      CONCLUSION: The study's protocol with a chemically defined cryoprotective
      solution, specific scalable bags constrained in an aluminum holder, and a storage
      temperature of -80 degrees C is promising for long-term adipose tissue
      cryopreservation.

PMID- 24675188
TI  - Factors associated with transfer of hand injuries to a level 1 trauma center: a
      descriptive analysis of 1147 cases.
AB  - BACKGROUND: The transfer of patients with hand injuries involves a commitment of
      substantial resources, emphasizing the importance of understanding factors that
      may influence referral patterns. Anecdotal experience suggests that the
      likelihood of transfer increases during nights and weekends. This study aimed to
      analyze patterns of hand trauma transfers to Duke University Medical Center with
      respect to timing and patient insurance status. METHODS: The authors performed a
      retrospective chart review and analysis of 1147 consecutive patient transfers
      from 2005 to 2010 at a single level 1 university trauma center. Data categories
      included timing of transfer, patient demographics, insurance status, diagnosis,
      and procedures performed. Statistical analysis was performed using SAS software
      (SAS Institute Inc., Cary, N.C.). RESULTS: Of the patient sample, 39.8 percent
      was female, 30 percent were African American, and 57.3 percent were white.
      Contrary to our expectations, transfers were more likely during the day (p =
      0.0001). Likewise, patients were more likely to present on weekdays than on
      weekends (p = .001). Although uninsured patients were not disproportionately
      represented overall, they were more frequently transferred at night (p = 0.0001),
      despite having the same complexity of injuries as privately insured patients.
      Conversely, patients with private insurance were less likely to be transferred at
      night (p = 0.0001). CONCLUSIONS: Similar to studies in other surgical
      specialties, this analysis demonstrates significant associations between
      insurance status and hand injury transfer patterns. The current climate,
      including declining numbers of surgeons willing to provide emergency hand care,
      diminishing reimbursements, and an expanding uninsured patient population,
      threatens to exacerbate these concerning trends in trauma patient management.

PMID- 24675189
TI  - Clinical outcomes in cranioplasty: risk factors and choice of reconstructive
      material.
AB  - BACKGROUND: Continuing advances in cranioplasty have enabled repair of
      increasingly complicated cranial defects. However, the optimal materials and
      approaches for particular clinical scenarios remain unclear. This study examines
      outcomes following cranioplasty for a variety of indications in patients treated
      with alloplastic material, autogenous tissue, or a combination of both. METHODS
      THE AUTHORS CONDUCTED: a retrospective analysis on 180 patients who had 195
      cranioplasties performed between 1993 and 2010. RESULTS: Materials used for
      cranioplasty included alloplastic for 42.6 percent (83 of 195), autologous for
      19.0 percent (37 of 195), and both combined for 38.5 percent (75 of 195). Mean
      defect size was 70.5 cm. A subset of patients had undergone previous irradiation
      (12.2 percent; 22 of 180) or had preoperative infections (30.6 percent; 55 of
      180). The most common complication was postoperative infection (15.9 percent; 31
      of 195). Factors that significantly predisposed to complications included
      preoperative radiation, previous infection, and frontal location. Preoperative
      radiation was the strongest predictor of having any postoperative complications,
      with an adjusted odds ratio of 6.91 (p < 0.005). Irradiated patients (OR, 7.96; p
      < 0.05) and patients undergoing frontal cranioplasties (OR, 2.83; p < 0.05) were
      more likely to require repeated operation. Preoperative infection predisposed
      patients to exposure of hardware in alloplastic reconstructions (OR, 3.13; p <
      0.05). CONCLUSIONS: Despite the evolution of cranioplasty techniques and
      materials, complications are not uncommon. The choice of reconstructive material
      may modify the risk of developing postoperative complications but appears less
      important than the clinical history in affecting outcome. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Risk, III.

PMID- 24675190
TI  - Combined orthognathic distraction procedure: Le Fort I maxillary osteotomy and
      mandibular curvilinear distraction osteogenesis. A new technique for craniofacial
      management.
AB  - Dentofacial deformities are traditionally treated by maxillary and mandibular
      osteotomies conducted separately or simultaneously. Recently, distraction
      osteogenesis has become an irreplaceable part of the surgical armamentarium, for
      its ability to induce new bone formation between the surfaces of bone segments
      that are gradually separated by incremental traction, along with a simultaneous
      expansion of the surrounding soft-tissue envelope. The aim of this article is to
      describe a combined surgical technique consisting of simultaneous maxillary Le
      Fort I advancement and mandibular surgical repositioning by means of bilateral
      sagittal split osteotomy with a curvilinear distractor based on a preliminary
      computerized presurgical prediction.

PMID- 24675191
TI  - Adjunctive techniques to traditional advancement procedures for treating severe
      blepharoptosis.
AB  - BACKGROUND: To create a more physiologic eyelid opening in patients with severe
      blepharoptosis, the authors used lamina propria mucosa of conjunctiva, which
      continues to the check ligament of the superior fornix, in addition to levator
      aponeurosis and Muller's muscle as a composite flap. In patients with epicanthal
      folds with associated telecanthus, the authors also performed epicanthoplasty
      with medial canthal tendon shortening. METHODS: Fifty blepharoptosis patients (85
      eyelids) with a degree of ptosis of greater than 4 mm underwent the advancement
      technique using the levator aponeurosis-Muller's muscle-lamina propria mucosa of
      conjunctiva as a composite flap. Twenty-one (42 percent) of those patients also
      underwent split V-W epicanthoplasty and plication of the medial canthal tendon
      for epicanthal folds with associated telecanthus. Degree of ptosis and levator
      function were measured preoperatively and postoperatively. RESULTS: Complete or
      near-complete correction of ptosis (degree of ptosis, <1 mm) was achieved in 54
      eyelids (63.5 percent) and mild residual ptosis (degree of ptosis, 1 to 2 mm) was
      observed in 22 eyelids (25.9 percent) in postoperative follow-up after 6 months.
      The most common complication was reoperation, which was done in 15 eyelids (17.6
      percent) because of incomplete correction. CONCLUSIONS: The advancement technique
      using the levator aponeurosis- Muller's muscle-lamina propria mucosa of
      conjunctiva composite was effective in the treatment of severe blepharoptosis
      with levator function of 2 to 7 mm. The technique produced elevating motion of
      the physiologic eyelid in a superior-posterior direction. There were no serious
      complications, such as long-term lagophthalmos or lid lag. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24675192
TI  - In-depth review of symptoms, triggers, and treatment of temporal migraine
      headaches (Site II).
AB  - BACKGROUND: This study was designed to report the details of the technique and
      assess the efficacy of surgical deactivation of temporal-triggered migraine
      headaches. It also examined the effect of surgical deactivation of temporal
      triggered migraine headaches on migraine triggers and associated symptoms besides
      the pain. METHODS: The authors analyzed the charts of 246 patients receiving
      surgery for temporal-triggered migraine headaches by a single surgeon (B.G.) over
      a 10-year period, who were followed for at least 1 year. Median regression
      adjusted for age, sex, and follow-up time was used to determine postoperative
      reduction in temporal-specific migraine headache index, which is the product of
      frequency, severity, and duration. The association between individual symptom or
      trigger resolution and index value reduction was studied by logistic regression.
      Details of the surgical treatment are discussed. RESULTS: Eighty-five percent of
      patients reported a successful surgery (>=50 percent improvement of headache
      index) at least 12 months after surgery (mean follow-up, 3 years). Fifty-five
      percent reported complete elimination of temporal migraine headache. Symptoms
      resolving with successful site II surgery included nausea, photophobia,
      phonophobia, difficulty concentrating, vomiting, blurry vision, and eyelid ptosis
      (p < 0.05). Triggers resolving included letdown after stress, air travel, missed
      meals, bright lights, loud noises, fatigue, weather change, and certain smells (p
      < 0.05). CONCLUSIONS: Surgical deactivation of temporal-triggered migraine
      headaches is effective regardless of age, sex, or follow-up time. Successful site
      II surgery is associated with changes in specific symptoms and triggers. This
      information can assist in trigger avoidance and contribute to constellations used
      for temporal-triggered migraine headaches trigger-site identification. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24675193
TI  - Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous
      melanoma.
AB  - BACKGROUND: Sentinel lymph node biopsy is the standard of care for intermediate
      depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared
      imaging have been used to aid in sentinel node biopsy. The present study aimed to
      determine the feasibility of sentinel lymph node biopsy with indocyanine green
      SPY Elite navigation and to critically evaluate the technique compared with the
      standard modalities. METHODS: A retrospective review of 90 consecutive cutaneous
      melanoma patients who underwent sentinel lymph node biopsy was performed. Two
      cohorts were formed: group A, which had sentinel lymph node biopsy performed with
      blue dye and radioisotope; and group B, which had sentinel lymph node biopsy
      performed with radioisotope and indocyanine green SPY Elite navigation. The
      cohorts were compared to assess for differences in localization rates,
      sensitivity and specificity of sentinel node identification, and length of
      surgery. RESULTS: The sentinel lymph node localization rate was 79.4 percent
      using the blue dye method, 98.0 percent using the indocyanine green fluorescence
      method, and 97.8 percent using the radioisotope/handheld gamma probe method.
      Indocyanine green fluorescence detected more sentinel lymph nodes than the vital
      dye method alone (p = 0.020). A trend toward a reduction in length of surgery was
      noted in the SPY Elite cohort. CONCLUSIONS: Sentinel lymph node mapping and
      localization in cutaneous melanoma with the indocyanine green SPY Elite
      navigation system is technically feasible and may offer several advantages over
      current modalities, including higher sensitivity and specificity, decreased
      number of lymph nodes sampled, decreased operative time, and potentially lower
      false-negative rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

PMID- 24675194
TI  - The internal pudendal artery perforator flap: free-style pedicle perforator flaps
      for vulva, vagina, and buttock reconstruction.
AB  - BACKGROUND: Reconstruction of the vulva, vagina, and buttocks following cancer
      ablation is challenging. Restoring the shape, volume, and function is the key to
      the best reconstruction for these regions. Perineal reconstruction with a free
      style flap based on skin perforators from the internal pudendal artery was
      evaluated. METHODS: The internal pudendal artery perforator flap was designed
      based on information about the skin perforators. The flap base contained the
      arterial sounds, which were identified by a handheld Doppler device, on and
      around the ischiorectal fossa. Types of flaps used included propeller flaps,
      traditional transposition flaps, and V-Y advancement flaps. RESULTS: Seventy-one
      flaps were transplanted in 45 cases. The reconstructed regions included vulvar
      skin in 36 cases, buttock skin in 10 cases, vagina in nine cases, anus in six
      cases, and pelvic cavity in six cases. The flaps were transplanted in the
      lithotomy or prone position. Sixty-seven of these flaps survived completely. Four
      flaps showed partial necrosis, but no total flap failures occurred. Thinning of
      the fatty tissue of the flap was performed in all cases except pelvic cavity
      reconstruction. An additional operation to remove bulkiness of the flaps
      following the initial reconstruction was required in one case. Propeller flaps,
      transposition flaps, and V-Y flaps were used in 35, three, and seven cases,
      respectively. CONCLUSIONS: This study revealed that the blood circulation of this
      flap is reliable and that it offers suitable volume not only for vulvar, vaginal,
      and anal reconstruction, which requires a thin flap, but also for pelvic floor
      reconstruction, which requires flap volume. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 24675195
TI  - The scope of plastic surgery according to 2434 allopathic medical students in the
      United States.
AB  - BACKGROUND: The general public and physicians often equate plastic surgery with
      cosmetic surgery. The authors investigate whether this perception is present in
      U.S. medical students. METHODS: A national survey of first- and second-year
      allopathic medical students was conducted. Students were asked to determine
      whether 46 specific procedures are performed by plastic surgeons: 12 aesthetic
      and 34 reconstructive procedures, which were further separated into three
      subgroups (general reconstruction and breast, craniofacial, and hand and lower
      extremity). RESULTS: Of the questionnaires sent out, 2434 from 44 medical schools
      were returned completed (23 percent response rate); 90.7 percent of aesthetic,
      66.0 percent of general reconstruction and breast, 51.0 percent of craniofacial,
      and 33.4 percent of hand and lower extremity procedures were correctly
      identified. There was no relationship with self-reported interest in plastic
      surgery (1 = not at all interested to 10 = extremely interested) and the number
      of correctly identified aesthetic procedures. However, there was a nonlinear
      relationship with correctly identified reconstructive procedures; compared to
      those with an interest level of 1 to 5, those who chose 10 scored on average 6.5
      points higher (14.2 versus 20.7) (p < 0.01). An anticipated career in surgery was
      associated with more correctly identified procedures across all sections but
      neither year (first versus second) nor region (Northeast, South, Central, West)
      with any section. CONCLUSIONS: U.S. medical students are unaware of the true
      scope of plastic surgery. Early exposure to basic aspects of plastic surgery
      could serve as a means of increasing interest and knowledge in the field and help
      educate future generations of referring physicians.

PMID- 24675197
TI  - "Plastic surgery"... beware.

PMID- 24675196
TI  - Manuscript rejection: how to submit a revision and tips on being a good peer
      reviewer.
AB  - Many instructional guides have been published on how to write scientific papers.
      Likewise, many published articles have focused on the reasons why submitted
      manuscripts are rejected. However, fewer publications have been presented to
      guide authors on how to address reviewers' comments in a manuscript revision.
      Even fewer counsel authors on how to deal with a rejection decision. In this
      article, the authors present a literature review on the strategies to get a
      manuscript accepted, despite an initial unfavorable review. The authors share
      their experience with addressing reviewers' comments to get a manuscript accepted
      and published. Finally, the authors discuss the process of peer review and offer
      tips on how to be an effective peer reviewer.

PMID- 24675199
TI  - Whom should we SPY? A cost analysis of laser-assisted indocyanine green
      angiography in prevention of mastectomy skin flap necrosis during prosthesis
      based breast reconstruction.
AB  - BACKGROUND: Skin flap necrosis is the most common complication following
      prosthesis-based breast reconstruction. Many studies have reported on the
      efficacy of laser-assisted indocyanine green angiography (SPY Elite System) in
      detecting flap necrosis. A cost-effectiveness analysis of laser-assisted
      indocyanine green angiography is lacking. METHODS: The authors performed a
      retrospective review of all consecutive immediate postmastectomy prosthesis-based
      reconstructions at the Brigham and Women's Hospital over a 7-year 10-month
      period. The rate of mastectomy skin flap necrosis and related implant loss was
      determined for the entire cohort and for the subgroups of patients at increased
      risk for developing this complication: smokers, obese patients, and patients with
      large breasts. Cost of treating implant loss and skin flap necrosis was
      calculated based on the average treatment courses and costs at the authors'
      institution. The cost of the SPY was obtained from LifeCell Corp. RESULTS: From
      January of 2004 through October of 2011, 79 of 710 prosthesis-based breast
      reconstructions (11.1 percent) developed mastectomy skin flap necrosis requiring
      excision and reclosure. Performing laser-assisted indocyanine green angiography
      on the entire cohort would result in an additional cost of $1537.30 per case of
      flap necrosis prevented. If laser-assisted indocyanine green angiography was
      performed on only these high-risk subgroups, the cost savings per case of flap
      necrosis prevented is $2098.80 for smokers, $5162.30 for patients with a body
      mass index greater than 30, and $1892.70 for patients with mastectomy weight
      greater than 800 g. CONCLUSION: Laser-assisted indocyanine green angiography is
      not cost-effective as a preventative measure for flap necrosis if used
      indiscriminately on all patients undergoing prosthesis-based breast
      reconstructions, but it is cost-effective for high-risk patients, such as
      smokers, obese patients, and patients with large breasts.

PMID- 24675201
TI  - Reversal of skin aging with topical retinoids.
AB  - Topical skin care and its place in plastic surgery today are often overlooked by
      clinicians formulating a plan for facial rejuvenation. Not only is it important
      to consider topical skin care as part of comprehensive care, but clinicians
      should also be educated with the data available in today's literature. This
      review aims to familiarize the reader with the biological processes of skin aging
      and evidence-based clinical outcomes afforded by various topical therapies.
      Furthermore, this review will focus on solar damage, the value of retinoids, and
      how they can be used in conjunction with forms of treatment such as chemical
      peel, dermabrasion, and lasers. Finally, guidelines will be provided to help the
      physician administer appropriate skin care based on the data presented.

PMID- 24675200
TI  - In vitro and in vivo investigation of the influence of implant surface on the
      formation of bacterial biofilm in mammary implants.
AB  - BACKGROUND: Capsular contracture remains the most common complication following
      breast augmentation surgery, and evidence suggests that bacterial biofilm on the
      implant surface is responsible. The authors investigated whether the interaction
      of bacterial biofilm with implants independently determines progression to
      capsule formation. They also studied the rate of bacterial growth and adhesion to
      implants. METHODS: Sixteen adult female pigs had 121 breast implants inserted.
      Sixty-six implants-23 smooth and 43 textured-were inoculated with a human strain
      of Staphylococcus epidermidis and received no other treatment. After an average
      period of 19 weeks, Baker grading was performed and implants were retrieved. For
      the in vitro study, samples underwent both quantitative bacterial analysis and
      imaging using confocal laser scanning and scanning electron microscopy. RESULTS:
      At explantation, there was no significant difference (p = 1.0) in the presence of
      capsular contracture (Baker grade III and IV) between smooth (83 percent) and
      textured implants (84 percent). Biofilm was confirmed on 60 of the 66 capsules.
      Capsules from smooth and textured implants had the same number of infecting
      bacteria (textured: 3.01 * 10 bacteria/g; smooth: 3.00 * 10 bacteria/g). In
      vitro, the surface of textured implants showed 11-, 43-, and 72-fold more
      bacteria at 2, 6, and 24 hours, respectively, compared with smooth implants (p <
      0.001). These findings were confirmed by imaging analysis. CONCLUSIONS: These
      results show that textured implants develop a significantly higher load of
      bacterial biofilm in comparison with smooth implants. Furthermore, in vivo, once
      a threshold of biofilm forms on either smooth or textured implant surfaces, there
      seems to be an equal propensity to progress to capsular contracture.

PMID- 24675202
TI  - Estrogen as a novel agent for induction of adipose-derived mesenchymal stem cells
      for osteogenic differentiation: in vivo bone tissue-engineering study.
AB  - BACKGROUND: This study investigated whether the in vivo osteogenic
      differentiation potential of adipose-derived mesenchymal stem cells is enhanced
      by 17beta-estradiol. METHODS: Thirty Sprague-Dawley rats were randomized and
      divided into five experimental groups. For the surgical procedure, biparietal
      full-thickness bone defects (7 mm in diameter) were created. A chitosan
      hydroxyapatite scaffold was used as the vehicle system for 17beta-estradiol
      loaded nanoparticles and adipose-derived mesenchymal stem cells. The first group,
      the blank defect group, was the control group. The defects were filled with
      either scaffold, estradiol, and scaffold; scaffold and adipose-derived
      mesenchymal stem cells; or estradiol, scaffold, and adipose-derived mesenchymal
      stem cells as experimental groups. The rats were killed at the end of weeks 4 and
      12, and their calvariae were harvested for histologic and microtomographic
      evaluation. RESULTS: Micro-computed tomographic evaluation of estradiol,
      scaffold, and adipose-derived mesenchymal stem cells revealed the highest median
      value (82.59 +/- 17.17), and the difference was significant compared with the
      blank defect group (p = 0.004). Histologic samples demonstrated a significant
      difference between experimental groups for bone defect repair at the end of weeks
      4 and 12 (p = 0.003 and p < 0.001). The estradiol, scaffold, and adipose-derived
      mesenchymal stem cell group had the highest median score (3.00 +/- 0.0) at week
      12, which was significantly higher than scores for the scaffold and adipose
      derived mesenchymal stem cell group and the blank defect group. CONCLUSION:
      17beta-Estradiol appears to be a novel and promising agent for future cell-based
      bone tissue-engineering studies.

PMID- 24675204
TI  - The dorsal homodigital island flap based on the dorsal branch of the digital
      artery: a review of 166 cases.
AB  - BACKGROUND: Soft-tissue reconstruction in the finger continues to evolve. This
      study reports reconstruction of small to moderate finger defects with the dorsal
      homodigital island flap and compares the results between the innervated and
      noninnervated flaps. METHODS: A retrospective study was conducted of 166 patients
      who had soft-tissue defects of the finger treated with the dorsal homodigital
      island flap (187 defects in 187 fingers in 166 patients). Mean defect size and
      flap size were 2.2 * 1.9 cm and 2.4 * 2.1 cm, respectively. When return of
      sensation was important, the dorsal branch of the digital nerve or the dorsal
      digital nerve was attached with the flap to restore neurosensory function. The
      main outcomes were static two-point discrimination and Semmes-Weinstein
      monofilament scores of the flap, fingertip pain, and joint motion. RESULTS: A
      significant difference was found between the innervated and noninnervated flaps
      in two-point discrimination, Semmes-Weinstein monofilament, and fingertip pain.
      The dual-innervated flap presented better discriminatory sensation on the flap
      and a lower incidence of fingertip pain than the noninnervated and single
      innervated flap. In addition, the innervated flap obtained better Semmes
      Weinstein monofilament scores than the noninnervated flap. For flaps harvested
      from the middle phalanx, the mean active motion arc of the distal interphalangeal
      joint was 69 degrees (range, 35 to 90 degrees). The contralateral side measured
      73 degrees (range, 45 to 90 degrees) (significant difference, p = 0.041). Maximum
      amplitude losses of 15 degrees were seen in 10 percent of patients in the distal
      interphalangeal joint. CONCLUSION: The dorsal homodigital island flap is an
      alternative for tissue reconstruction in the finger. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 24675203
TI  - Does empiric antibiotic therapy change MRSA [corrected] hand infection outcomes?
      Cost analysis of a randomized prospective trial in a county hospital.
AB  - BACKGROUND: The incidence of community-acquired methicillin-resistant
      Staphylococcus aureus infections is rising at an alarming pace. Effective
      treatment has historically involved early debridement and antibiotic
      administration. This study was designed to prospectively determine the
      effectiveness of empiric therapy in treating hand infections. METHODS: A
      prospective randomized trial was conducted at a level I county hospital. Patients
      with a hand infection received either empiric intravenous vancomycin at admission
      or intravenous cefazolin. Outcomes were tracked using severity of infection,
      appropriate clinical response, and length of stay. Cost-effectiveness was
      calculated using total cost for each patient in both groups. Statistical analyses
      were performed. RESULTS: Forty-six patients were enrolled in the study. Twenty
      four were randomized to cefazolin (52.2 percent) and 22 (47.8 percent) to
      vancomycin. There was no statistical difference between cost of treatment (p <
      0.20) or mean length of stay (p < 0.18) between the groups. Patients randomized
      to cefazolin had higher mean costs of treatment compared with patients who were
      randomized to vancomycin (p < 0.05). Patients with more severe infections had
      more expensive mean costs of treatment (p < 0.0001) and longer mean length of
      stay (p = 0.0002). Near the end of the study, the incidence of community-acquired
      methicillin-resistant S. aureus at the authors' county hospital was discovered to
      be 72 percent, which caused the study to be terminated prematurely by the
      institutional review board because of the high incidence precluding further
      randomization. CONCLUSIONS: Appropriate early treatment for methicillin-resistant
      S. aureus has not been definitively established. No difference in outcome using
      cefazolin versus vancomycin as a first-line agent was identified.

PMID- 24675205
TI  - Reliability of nasolabial anthropometric measures using three-dimensional
      stereophotogrammetry in infants with unrepaired unilateral cleft lip.
AB  - BACKGROUND: Surgical and orthodontic treatment of unilateral cleft lip +/- palate
      can produce dramatic changes in nasolabial form; however, the lack of ideal
      methods with which to objectively document three-dimensional form limits the
      ability to assess treatment outcomes. The purpose of this study was to determine
      the reliability of three-dimensional stereophotogrammetry for anthropometric
      assessment of the unilateral cleft lip +/- palate deformity in infants before
      cleft lip repair. METHODS: Preoperative three-dimensional images were acquired
      from 26 consecutive patients with unrepaired unilateral cleft lip +/- palate.
      Three raters performed indirect anthropometry on each image on two separate
      occasions, with at least 1 week between rating sessions. One rater performed
      direct measurements on participants before surgery while in the operating room.
      Twenty-six linear and angular measurements were considered, and intrarater,
      interrater, and intermethod reliability were assessed. RESULTS: Regarding
      intrarater and interrater reliability, most measurements had Pearson coefficients
      greater than 0.75, mean differences less than 0.8 mm, and mean proportional
      differences less than 0.1. For measurements involving vermilion height, nostril
      remnants, or Cupid's bow width, Pearson coefficients ranged from 0.3 to 0.75,
      mean differences ranged from 0.4 to 0.9 mm, and mean proportional differences
      ranged from 0.1 to 0.3. Regarding intermethod reliability, correlation
      coefficients ranged from 0.4 to 0.75 for most measurements. The mean differences
      for nose and lip measurements were less than 1 mm and between 0.8 and 1.3 mm,
      respectively. CONCLUSION: Three-dimensional stereophotogrammetry provides a
      reliable method for many anthropometric measurements of nasolabial form in
      infants with unrepaired unilateral cleft lip +/- palate. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Diagnostic, II.

PMID- 24675206
TI  - Characterization, prophylaxis, and treatment of infectious complications in
      craniomaxillofacial and upper extremity allotransplantation: a multicenter
      perspective.
AB  - BACKGROUND: Vascularized composite allotransplants consist of heterogeneous
      tissues from different germ layers, which include skin, muscle, bone, fat,
      nerves, and lymph nodes. The antigenic diversity of these tissues, particularly
      of the highly immunogenic skin component, necessitates potent immunosuppressive
      regimens similar to that of some solid organ transplants. Indeed, the lifelong,
      high-dose, multidrug immunosuppressive protocols expose vascularized composite
      allotransplant recipients to considerable risk of infectious, metabolic, and
      neoplastic sequelae. In this article, the authors review the infectious risk to
      patients after vascularized composite allotransplantation, with special attention
      to the somewhat limited experience with the prophylaxis and treatment of
      infections after this innovative reconstructive surgery. METHODS: A review of the
      literature was undertaken to elucidate the characterization, prophylaxis, and
      treatment of all documented infectious complications. RESULTS: Infections in face
      and hand vascularized composite allotransplants follow a course similar to that
      of solid organ transplants. Several differences exist, including the unique flora
      of craniomaxillofacial transplants, the increased risk of donor-derived
      infections, and the alteration of the risk-to-benefit ratio for cytomegalovirus
      infections. CONCLUSIONS: The patient with a face or limb transplant has many of
      the same infectious risks as a lung transplant recipient, which include
      bacterial, viral, and fungal infections. Because of the anatomy, mucosal
      exposure, and differing donor flora, however, the face or limb transplant is
      susceptible to invasive diseases from a variety of microbes.

PMID- 24675207
TI  - The effects of immunosuppressive medications on outcomes in microvascular free
      tissue transfer.
AB  - BACKGROUND: Reported 10-year patient survival after liver transplantation is
      nearing 70 percent, with similar trends seen for kidney transplantation. With
      increasing life expectancy, these patients have an increased need for
      posttransplant reconstructive surgery. Thus, plastic surgeons must know the
      effects of immunosuppressive medications on outcomes in microvascular
      reconstruction. METHODS: A retrospective review was performed on all
      immunosuppressed solid-organ transplant patients who underwent subsequent free
      tissue transfer of all types, over an 8-year period. Patient demographics, type
      of solid organ transplant, immunosuppressive regimen, anticoagulation regimen,
      associated medical comorbidities, and complication rates were analyzed. RESULTS:
      Twenty-four microvascular free tissue transfers were performed over an 8-year
      period on immunosuppressed patients, for head and neck and lower extremity
      reconstruction. Fifteen patients (63 percent) underwent prior kidney transplant,
      seven (29 percent) underwent prior liver transplant, and two (8 percent)
      underwent prior lung transplant. Prednisone (79 percent of patients),
      cyclosporine (33 percent), and tacrolimus (33 percent) were the most commonly
      used immunosuppressive medications. Complications included one total flap loss (4
      percent), three intraoperative arterial thromboses (13 percent), and two
      postoperative venous thromboses (8 percent). Univariate analysis illustrated a
      statistically significant association between prednisone and overall complication
      rate (p = 0.032). CONCLUSIONS: Microvascular free tissue transfer is a challenge
      in immunosuppressed patients. Univariate analysis showed prednisone to correlate
      statistically with operative morbidity. Transplant patients receiving prednisone
      at the time of their elective free flap procedure will require additional care to
      lower the additional risk of delayed wound healing, partial flap loss, and
      anastomotic thrombosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 24675208
TI  - Use of morphometric assessment of body composition to quantify risk of surgical
      site infection in patients undergoing component separation ventral hernia repair.
AB  - BACKGROUND: Body mass index does not allow accurate risk stratification for
      individuals undergoing component separation repair of ventral hernias. The
      authors hypothesized that tissue morphology measurements (morphomics) of
      preoperative computed tomography scans stratify the risk of surgical site
      infection in patients undergoing ventral hernia repair with a component
      separation technique. METHODS: The authors identified 93 patients who underwent
      component release ventral hernia repair (2004 to 2012). The surgical technique
      involved release of the external oblique muscle lateral to the linea semilunaris.
      Using analytic morphomic techniques, the authors measured patients' morphology
      using routine preoperative computed tomography scans. Two-sample t test was used
      to evaluate the effect of morphomic and demographic factors on surgical-site
      infection. Separate logistic regression analyses were performed on these
      morphomic factors to evaluate their predictive value in assessing the risk of
      surgical site infection, controlling for demographic covariates. RESULTS:
      Surgical site infections were observed in 31 percent (n = 29) of the population.
      Subcutaneous fat area, total body area, and total body circumference had
      increased odds ratios for surgical site infection (p = 0.004, 0.014, and 0.012,
      respectively), indicating that these measures are better associated with surgical
      site infection than body mass index. These calculations control for demographic
      covariates, confirming that these morphomic parameters are predictive of surgical
      site infection. CONCLUSION: Specific morphomic values serve as superior
      predictors of surgical site infection in patients undergoing component separation
      technique hernia repair than currently used values such as body mass index.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24675209
TI  - Breast augmentation.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Assess patient physical characteristics that influence implant selection.
      2. Adopt a system to aid in implant size selection. 3. Become cognizant of the
      advantages and disadvantages of incision, pocket plane, and implant options. 4.
      Understand implant positioning concepts and aseptic implant handling methods. 5.
      Manage untoward postoperative sequelae 6. Understand secondary surgery concepts.
      SUMMARY: Breast augmentation is the most commonly performed aesthetic surgical
      procedure. Choices of incisions, pocket plane, and myriad implant characteristics
      constitute the basis for surgical planning. Analysis of physical characteristics
      and inclusion of the patient in implant selection contribute to overall
      satisfaction and reduce requests for secondary surgery. Technical expertise in
      implant positioning and aseptic handling helps to prevent capsular contracture,
      implant malposition, and other shape problems. Despite the need for secondary
      surgery in some, patient satisfaction is high.

PMID- 24675210
TI  - A methodological analysis of the plastic surgery cost-utility literature using
      established guidelines.
AB  - BACKGROUND: Cost-utility studies, common in medicine, are rare within plastic
      surgery despite their capability of measuring the value of procedures by
      considering the societal costs of improving quality of life. The objectives of
      this study were to analyze the design quality of the plastic surgery cost-utility
      literature and to identify areas of needed improvement for future studies.
      METHODS: A scoring tool was constructed based on the Recommendations of the Panel
      on Cost-Effectiveness in Health and Medicine. A PubMed search through October of
      2012 was conducted for English-language plastic surgery utility studies. Articles
      were selected using two inclusion criteria and evaluated using the scoring tool.
      RESULTS: A 9-point scoring tool was created, and 37 publications were selected.
      Their average score was 3 out of 9 points. Thirty studies (81 percent) used
      population preferences in utility measurements. Fifteen studies (41 percent)
      measured costs, but only four (11 percent) included indirect costs and only five
      (14 percent) applied discount rates to calculate the value of treatments over
      time. Three studies (8 percent) earned zero points. The highest scoring study
      earned 8 points. CONCLUSIONS: The identified studies manifest the potential of
      cost-utility analyses in plastic surgery. Nonetheless, they are inconsistent in
      applying established cost-utility guidelines, especially in measuring costs and
      conducting recommended sensitivity analysis. Following this simple scoring tool
      can help future studies achieve some necessary improvements.

PMID- 24675211
TI  - Magnetic resonance imaging and ultrasound evaluation after breast autologous fat
      grafting combined with platelet-rich plasma.

PMID- 24675212
TI  - Quality-of-life outcomes between mastectomy alone and breast reconstruction:
      comparison of patient-reported BREAST-Q and other health-related quality-of-life
      measures.

PMID- 24675213
TI  - Reply: quality-of-life outcomes between mastectomy alone and breast
      reconstruction: comparison of patient-reported breast-Q and other health-related
      quality-of-life measures.

PMID- 24675214
TI  - Three-dimensional simulated images in breast augmentation surgery: an
      investigation of patients' satisfaction and the correlation between prediction
      and actual outcome.

PMID- 24675215
TI  - Analgesic efficacy of Lidocaine for suction-assisted lipectomy with tumescent
      technique under general anesthesia: a randomized, double-masked, controlled
      trial.

PMID- 24675216
TI  - Reply: analgesic efficacy of lidocaine for suction-assisted lipectomy with
      tumescent technique under general anesthesia: a randomized, double-masked,
      controlled trial.

PMID- 24675217
TI  - Plastic surgery improves long-term weight control after bariatric surgery.

PMID- 24675218
TI  - Reply: plastic surgery improves long-term weight control after bariatric surgery.

PMID- 24675219
TI  - Are the new changes in our operating rooms really making us safer and better
      surgeons?

PMID- 24675220
TI  - Reply: are the new changes in our operating rooms really making us safer and
      better surgeons?

PMID- 24675221
TI  - Congenital heart disease in pregnancy.
AB  - The story of congenital heart disease is one of the major successes of medicine
      in the last 50 years. Heart conditions previously associated with early death are
      now successfully treated. Many of these women are now in their child-bearing
      years wishing to have children of their own. All of these women should be offered
      comprehensive pre-conception counselling by a dedicated multi-disciplinary team.
      Each woman will present a unique set of cardiac and obstetric challenges that
      require an individualised assessment of risk and a carefully documented care
      plan. In this chapter, I describe the most common forms of congenital heart
      disease and the specific issues that should be assessed before conception. I
      present a systematic approach to risk stratification and care planning. These
      lesions range from mild disease with little implications for pregnancy to those
      with a sizable risk of maternal mortality or complications. I will also discuss
      fetal risk factors. 

PMID- 24675222
TI  - Growing Neural Gas approach for obtaining homogeneous maps by restricting the
      insertion of new nodes.
AB  - The Growing Neural Gas model is used widely in artificial neural networks.
      However, its application is limited in some contexts by the proliferation of
      nodes in dense areas of the input space. In this study, we introduce some
      modifications to address this problem by imposing three restrictions on the
      insertion of new nodes. Each restriction aims to maintain the homogeneous values
      of selected criteria. One criterion is related to the square error of
      classification and an alternative approach is proposed for avoiding additional
      computational costs. Three parameters are added that allow the regulation of the
      restriction criteria. The resulting algorithm allows models to be obtained that
      suit specific needs by specifying meaningful parameters.

PMID- 24675223
TI  - Pycnogenol(r) improves cognitive function, attention, mental performance and
      specific professional skills in healthy professionals aged 35-55.
AB  - AIM: This 12-week, product-evaluation registry study aimed to compare the effects
      of supplementation with French Pine Bark Extract (Pycnogenol(r)) on cognitive
      function, attention, and mental performance in healthy professionals with
      increased oxidative stress in a professional context. METHODS: Professionals were
      screened for increased oxidative stress: 60 subjects (range 35-55 years, no risk
      conditions, no addictions) voluntarily decided to be followed-up. Diet, alcohol
      and lifestyle patterns, including exercise, were controlled. Pycnogenol(r) (150
      mg/day) was used in combination with a health plan to enhance mental performance
      and control oxidative stress. RESULTS: A group of 30 professionals used
      Pycnogenol(r), and 29 acted as comparable controls for a period of 12 weeks. The
      two registry groups were comparable. Cognitive function, attention, mental
      performance, sustained attention, memory, executive functions, mood and oxidative
      stress values were comparable at inclusion. At 12 weeks the improvement in
      Pycnogenol(r) subjects was more significant than in controls. Plasma-free
      radicals (oxidative stress) were significantly decreased (median -30.4%) at 12
      weeks in Pycnogenol(r) subjects in comparison with a non-significant variation
      observed in controls (+0.9%; difference between groups). Considering the
      cognitive test battery (PASAT, pattern recognition memory, spatial recognition
      memory, spatial working memory), Pycnogenol(r) subjects showed a small but
      significant improvement with spatial recognition memory unchanged. Mood
      parameters (alertness, anxiety, contentedness) also improved in professionals
      using the supplement. In the evaluation of 12 professional daily tasks all items
      were improved with Pycnogenol(r) supplementation. The score relative to semi
      professional minitasks was improved more in Pycnogenol(r) subjects. Tolerability
      and compliance were optimal with >94% of the doses of supplement correctly used.
      CONCLUSION: Pycnogenol(r) supplementation for 12 weeks appears to improve
      cognitive function and oxidative stress in healthy professionals.

PMID- 24675224
TI  - Supported liquid membrane as a novel tool for driving the equilibrium of omega
      transaminase catalyzed asymmetric synthesis.
AB  - An attractive option to produce chiral amines of industrial importance is through
      asymmetric synthesis using omega-transaminase. However, reaching high yields
      often requires a strategy for shifting the equilibrium position. This paper
      describes a novel strategy for handling this problem. It involves the use of a
      supported liquid membrane (SLM) together with a packed bed reactor. The reactor
      contains Escherichia coli cells with omega-transaminase from Arthrobacter
      citreus, immobilized by flocculation with chitosan. The SLM consists of a hollow
      fibre membrane contactor in which the pores contain undecane. The system enables
      continuous extraction of the amine product and was used to successfully shift the
      equilibrium in asymmetric synthesis of (S)-alpha-methylbenzylamine (MBA). A
      conversion of 98% was reached, compared to 50% without product extraction.
      Moreover, a selective extraction of the produced MBA was realized. A high product
      concentration of 55g/l was reached after 80h, and the system showed promising
      potential for continuous operation. 

PMID- 24675225
TI  - Aqueous extract of Glycyrrhiza inflata inhibits aggregation by upregulating
      PPARGC1A and NFE2L2-ARE pathways in cell models of spinocerebellar ataxia 3.
AB  - Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 and
      dentatorubropallidoluysian atrophy, as well as Huntington disease, are a group of
      neurodegenerative disorders caused by a CAG triplet-repeat expansion encoding a
      long polyglutamine (polyQ) tract in the respective mutant proteins. The
      cytoplasmic and nuclear aggregate formation, a pathological hallmark of polyQ
      diseases, is probably the initial process triggering the subsequent pathological
      events. Compromised oxidative stress defense capacity and mitochondrial
      dysfunction have emerged as contributing factors to the pathogenesis of polyQ
      diseases. The roots of licorice (Glycyrrhiza species) have long been used as an
      herbal medicine. In this study, we demonstrate the aggregate-inhibitory effect of
      Glycyrrhiza inflata herb extract and its constituents licochalcone A and ammonium
      glycyrrhizinate (AMGZ) in both 293 and SH-SY5Y ATXN3/Q75 cells, SCA3 cell models.
      The reporter assay showed that G. inflata herb extract, licochalcone A, and AMGZ
      could enhance the promoter activity of peroxisome proliferator-activated receptor
      gamma, coactivator 1alpha (PPARGC1A), a known regulator of mitochondrial
      biogenesis and antioxidative response genes. G. inflata extract, licochalcone A,
      and AMGZ upregulated PPARGC1A expression and its downstream target genes, SOD2
      and CYCS, in the 293 ATXN3/Q75 cell model. The expression of nuclear factor
      erythroid 2-related factor 2 (NFE2L2), the principal transcription factor that
      binds to antioxidant-responsive elements (AREs) to promote ARE-dependent gene
      expression when the cells respond to oxidative stress, and its downstream genes,
      HMOX1, NQO1, GCLC, and GSTP1, was also increased by G. inflata herb extract,
      licochalcone A, and AMGZ. Knockdown of PPARGC1A increased aggregates in ATXN3/Q75
      cells and also attenuated the aggregate-inhibiting effect of the tested
      compounds. G. inflata extract and its constituents significantly elevated
      GSH/GSSG ratio and reduced reactive oxidative species in ATXN3/Q75 cells. The
      study results suggest that the tested agents activate PPARGC1A activity and
      NFE2L2-ARE signaling to increase mitochondrial biogenesis, decrease oxidative
      stress, and reduce aggregate formation in SCA3 cellular models. 

PMID- 24675226
TI  - Redox proteomics analysis of HNE-modified proteins in Down syndrome brain: clues
      for understanding the development of Alzheimer disease.
AB  - Down syndrome (DS) is the most common genetic cause of intellectual disability,
      due to partial or complete triplication of chromosome 21. DS subjects are
      characterized by a number of abnormalities including premature aging and
      development of Alzheimer disease (AD) neuropathology after approximately 40 years
      of age. Several studies show that oxidative stress plays a crucial role in the
      development of neurodegeneration in the DS population. Increased lipid
      peroxidation is one of the main events causing redox imbalance within cells
      through the formation of toxic aldehydes that easily react with DNA, lipids, and
      proteins. In this study we used a redox proteomics approach to identify specific
      targets of 4-hydroxynonenal modifications in the frontal cortex from DS cases
      with and without AD pathology. We suggest that a group of identified proteins
      followed a specific pattern of oxidation in DS vs young controls, probably
      indicating characteristic features of the DS phenotype; a second group of
      identified proteins showed increased oxidation in DS/AD vs DS, thus possibly
      playing a role in the development of AD. The third group of comparison, DS/AD vs
      old controls, identified proteins that may be considered specific markers of AD
      pathology. All the identified proteins are involved in important biological
      functions including intracellular quality control systems, cytoskeleton network,
      energy metabolism, and antioxidant response. Our results demonstrate that
      oxidative damage is an early event in DS, as well as dysfunctions of protein
      degradation systems and cellular protective pathways, suggesting that DS subjects
      are more vulnerable to oxidative damage accumulation that might contribute to AD
      development. Further, considering that the majority of proteins have been already
      demonstrated to be oxidized in AD brain, our results strongly support
      similarities with AD in DS. 

PMID- 24675227
TI  - Mitochondrial aldehyde dehydrogenase 2 accentuates aging-induced cardiac
      remodeling and contractile dysfunction: role of AMPK, Sirt1, and mitochondrial
      function.
AB  - Cardiac aging is associated with compromised myocardial function and morphology
      although the underlying mechanism remains elusive. Aldehyde dehydrogenase 2
      (ALDH2), an essential mitochondrial enzyme governing cardiac function, displays
      polymorphism in humans. This study was designed to examine the role of ALDH2 in
      aging-induced myocardial anomalies. Myocardial mechanical and intracellular
      Ca(2+) properties were examined in young (4-5 months) and old (26-28 months) wild
      type and ALDH2 transgenic mice. Cardiac histology, mitochondrial integrity, O2(-)
      generation, apoptosis, and signaling cascades, including AMPK activation and
      Sirt1 level were evaluated. Myocardial function and intracellular Ca(2+) handling
      were compromised with advanced aging; the effects were accentuated by ALDH2.
      Hematoxylin and eosin and Masson trichrome staining revealed cardiac hypertrophy
      and interstitial fibrosis associated with greater left-ventricular mass and wall
      thickness in aged mice. ALDH2 accentuated aging-induced cardiac hypertrophy but
      not fibrosis. Aging promoted O2(-) release, apoptosis, and mitochondrial injury
      (mitochondrial membrane potential, levels of UCP-2 and PGC-1alpha), and the
      effects were also exacerbated by ALDH2. Aging dampened AMPK phosphorylation and
      Sirt1, the effects of which were exaggerated by ALDH2. Treatment with the ALDH2
      activator Alda-1 accentuated aging-induced O2(-) generation and mechanical
      dysfunction in cardiomyocytes, the effects of which were mitigated by cotreatment
      with activators of AMPK and Sirt1, AICAR, resveratrol, and SRT1720. Examination
      of human longevity revealed a positive correlation between life span and ALDH2
      gene mutation. Taken together, our data revealed that ALDH2 enzyme may accentuate
      myocardial remodeling and contractile dysfunction in aging, possibly through
      AMPK/Sirt1-mediated mitochondrial injury. 

PMID- 24675229
TI  - Distribution and associated factors of optic disc diameter and cup-to-disc ratio
      in an elderly Chinese population.
AB  - BACKGROUND: Glaucoma is the second leading cause of blindness worldwide and East
      Asian people account for almost half of those affected. Vertical elongation of
      the optic cup is a characteristic feature of glaucoma. However, there is a
      significant overlap in the vertical cup-to-disc ratio (VCDR) between normal eyes
      and eyes affected by glaucoma. The purpose of this study was to determine the
      distribution of VCDR and vertical disc diameter (VDD) and their predictive
      factors in a population of elderly Chinese residents in Taiwan. METHODS: Four
      hundred and sixty elderly Chinese residents aged 72 years and older in the
      Shihpai district, Taipei, Taiwan participated in this study. Slit lamp
      biomicroscopic measurement of the VCDR and VDD after pupil dilation with a 78
      diopter lens was performed by one glaucoma specialist. Multiple linear regression
      analyses were used to fit the best model for independent variables. RESULTS: The
      VCDR was recorded for 438 right eyes and 430 left eyes. After excluding
      participants with glaucoma, the mean +/- SD VCDR was 0.44 +/- 0.17 for both eyes,
      and the 97.5(th) percentile was 0.8. A greater VCDR was associated with a longer
      axial length [VCDR = -0.47 + 0.04(axial length)] under multiple regression
      analysis. The VDD was obtained for 420 right eyes and 406 left eyes. The mean +/-
      SD VDD for all participants was 1.77 +/- 0.22 mm for the right eye and 1.79 +/-
      0.22 mm for the left eye. A higher body mass index (BMI) and a longer axial
      length were significantly associated with a larger VDD under multiple regression
      analysis. [VDD = -0.05 + 0.07 (axial length) + 0.06 (obesity); if BMI <24, then
      obesity = 0; if BMI >= 24, then obesity = 1]. A larger VDD was associated with a
      larger VCDR (p < 0.001) and the VCDR could be predicted by the equation VCDR = 
      0.07 + 0.3VDD. CONCLUSION: A greater VCDR was related to a longer axial length. A
      greater VDD was related to a higher BMI and a longer axial length.

PMID- 24675228
TI  - alpha-Lipoic acid protects mitochondrial enzymes and attenuates
      lipopolysaccharide-induced hypothermia in mice.
AB  - Hypothermia is a key symptom of sepsis, but the mechanism(s) leading to
      hypothermia during sepsis is largely unknown and thus no effective therapy is
      available for hypothermia. Therefore, it is important to investigate the
      mechanism and develop effective therapeutic methods. Lipopolysaccharide (LPS)
      induced hypothermia accompanied by excess nitric oxide (NO) production leads to a
      reduction in energy production in wild-type mice. However, mice lacking inducible
      nitric oxide synthase did not suffer from LPS-induced hypothermia, suggesting
      that hypothermia is associated with excess NO production during sepsis. This
      observation is supported by the treatment of wild-type mice with alpha-lipoic
      acid (LA) in that it effectively attenuates LPS-induced hypothermia with
      decreased NO production. We also found that LA partially restored ATP production,
      and activities of the mitochondrial enzymes involved in energy metabolism, which
      were inhibited during sepsis. These data suggest that hypothermia is related to
      mitochondrial dysfunction, which is probably compromised by excess NO production
      and that LA administration attenuates hypothermia mainly by protecting
      mitochondrial enzymes from NO damage. 

PMID- 24675230
TI  - Strategies for the evaluation and selection of potential vaginal probiotics from
      human sources: an exemplary study.
AB  - During the last years, the application of probiotics in gynaecological clinical
      practice has gained increasing relevance regarding therapy and prevention. This
      trend has also provoked the need for having tailored pharmaceutical preparations
      containing powerful microbial strains with defined properties. For the
      development of such preparations, several factors and criteria have to be
      considered, thereby not only focusing on identity and safety aspects as well as
      individual properties of the bacterial strains, but also on technological issues,
      such as stability and targeted release from the preparation. Against this
      background, this report exemplarily addresses the development procedure of a
      probiotic bacterial formulation for gynaecological application, covering the
      search for suitable strains, assessing their microbiological, molecular
      biological and physiological characterisation, and the selection for their use in
      clinical trials. In detail, starting with 127 presumptive lactobacilli isolates
      of vaginal origin, a step-by-step selection of candidate strains meeting special
      criteria was thoroughly examined, finally leading to a preparation consisting of
      four individual Lactobacillus strains that possess particular significance in
      women's urogenital health. Relevant issues and quality criteria of probiotic
      preparations used in gynecology are addressed and exemplarily introduced.

PMID- 24675231
TI  - Probiotic 'glow of health': it's more than skin deep.
AB  - Radiant skin and hair are universal indicators of good health. It was recently
      shown that feeding of probiotic bacteria to aged mice rapidly induced youthful
      vitality characterised by thick lustrous skin and hair, and enhanced reproductive
      fitness, not seen in untreated controls. Probiotic-treated animals displayed
      integrated immune and hypothalamic-pituitary outputs that were isolated
      mechanistically to microbe-induced anti-inflammatory interleukin-10 and
      neuropeptide hormone oxytocin. In this way, probiotic microbes interface with
      mammalian physiological underpinnings to impart superb physical and reproductive
      fitness displayed as radiant and resilient skin and mucosae, unveiling novel
      strategies for integumentary health. 

PMID- 24675232
TI  - Gut carbohydrate metabolism instead of fat metabolism regulated by gut microbes
      mediates high-fat diet-induced obesity.
AB  - The aim of this study was to investigate the mechanisms underlying the
      involvement of gut microbes in body weight gain of high-fat diet-fed obesity
      prone (obese) and obesity-resistant (lean) mice. C57BL/6 mice were grouped into
      an obese group, a lean group and a normal control group. Both obese and lean mice
      were fed a high-fat diet while normal control mice were fed a normal diet; they
      were observed for six weeks. The results showed that lean mice had lower serum
      lipid levels, body fat and weight gain than obese mice. The ATPase, succinate
      dehydrogenase and malate dehydrogenase activities in liver as well as oxygen
      expenditure and rectal temperature of lean mice were significantly lower than in
      obese mice. As compared with obese mice, the absorption of intestinal
      carbohydrates but not of fats or proteins was significantly attenuated in lean
      mice. Furthermore, 16S rRNA abundances of faecal Firmicutes and Bacteroidetes
      were significantly reduced in lean mice. In addition, faecal beta-D-galactosidase
      activity and short chain fatty acid levels were significantly decreased in lean
      mice. Expressions of peroxisome proliferator-activated receptor gamma 2 and
      CCAAT/enhancer binding protein-beta in visceral adipose tissues were
      significantly downregulated in lean mice as compared with obese mice. Resistance
      to dyslipidaemia and high-fat diet-induced obesity was mediated by ineffective
      absorption of intestinal carbohydrates but not of fats or proteins, probably
      through reducing gut Bacteroidetes and Firmicutes contents and lowering of gut
      carbohydrate metabolism. The regulation of intestinal carbohydrates instead of
      fat absorption by gut microbes might be a potential treatment strategy for high
      fat diet-induced obesity. 

PMID- 24675234
TI  - Update on testicular germ cell tumors.
AB  - PURPOSE OF REVIEW: This overview discusses several important developments in
      testicular germ cell tumors (TGCTs) over the past year. RECENT FINDINGS: Genomic
      studies continue to investigate gene expression as possible markers for disease
      relapse and metastatic potential. Optimal treatment strategies for early-stage
      seminomas continue to evolve toward surveillance versus chemotherapy, although
      developing radiation delivery modalities may ultimately provide a safe
      alternative. The role of retroperitoneal lymph node dissection in postorchiectomy
      early-stage nonseminoma germ cell tumors remains a topic of debate. SUMMARY:
      Treatment paradigms continue to be refined for TGCTs as research in these areas
      continues.

PMID- 24675233
TI  - Renal cell carcinoma: molecular biology and targeted therapy.
AB  - PURPOSE OF REVIEW: Renal cell carcinoma (RCC) continues to be the subject of
      vigorous clinical and translational investigation. Advances in systemic targeted
      therapies, new molecular pathways and immunotherapy approaches will be discussed.
      RECENT FINDINGS: Agents targeting the vascular endothelial growth factor (VEGF)
      and/or the mammalian target of rapamycin (mTOR) pathways continue to be the
      mainstay for treating metastatic RCC (mRCC). Although enhanced target specificity
      has improved the toxicity profile associated with newer VEGF-pathway antagonists,
      durable complete responses remain the exception. Identification of novel
      pathways/agents, as well as the optimal sequencing and combination of existing
      targeted agents, remain areas of active study. In addition, emerging data from
      early clinical trials have reinvigorated interest in immunomodulatory agents.
      SUMMARY: The therapeutic armamentarium available to genitourinary oncologists
      continues to grow, but much work remains to be done to fully realize the
      potential of pathway-specific targeted strategies and immune-based approaches for
      mRCC.

PMID- 24675236
TI  - Integrated visualization of a multi-omics study of starvation in mouse intestine.
AB  - Our understanding of complex biological processes can be enhanced by combining
      different kinds of high-throughput experimental data, but the use of incompatible
      identifiers makes data integration a challenge. We aimed to improve methods for
      integrating and visualizing different types of omics data. To validate these
      methods, we applied them to two previous studies on starvation in mice, one using
      proteomics and the other using transcriptomics technology. We extended the
      PathVisio software with new plugins to link proteins, transcripts and pathways. A
      low overall correlation between proteome and transcriptome data was detected
      (Spearman rank correlation: 0.21). At the level of individual genes, correlation
      was highly variable. Many mRNA/protein pairs, such as fructose biphosphate
      aldolase B and ATP Synthase, show good correlation. For other pairs, such as
      ferritin and elongation factor 2, an interesting effect is observed, where mRNA
      and protein levels change in opposite directions, suggesting they are not
      primarily regulated at the transcriptional level. We used pathway diagrams to
      visualize the integrated datasets and found it encouraging that transcriptomics
      and proteomics data supported each other at the pathway level. Visualization of
      the integrated dataset on pathways led to new observations on gene-regulation in
      the response of the gut to starvation. Our methods are generic and can be applied
      to any multi-omics study. The PathVisio software can be obtained at
      http://www.pathvisio.org. Supplemental data are available at
      http://www.bigcat.unimaas.nl/data/jib-supplemental/ , including instructions on
      reproducing the pathway visualizations of this manuscript. 

PMID- 24675235
TI  - Pentraxin 3 promotes oxLDL uptake and inhibits cholesterol efflux from macrophage
      derived foam cells.
AB  - BACKGROUND: The objective of this study was to determine the effects of
      pentraxin3 (PTX3) on human oxidized low density lipoprotein (oxLDL) uptake and
      cholesterol efflux from human macrophage foam cells, which may play a critical
      role in atherogenesis. METHODS: The effects of PTX3 on oxLDL uptake and
      cholesterol efflux were determined after transfection of human THP-1 macrophages
      with pSG5hPTX3 or PTX3siRNA plasmids. To evaluate the role of specific signaling
      pathways, human THP-1 cells were pre-treated with inhibitors of the extracellular
      signal-regulated protein kinases 1 and 2 (ERK1/2), phosphatidylinositide 3
      kinases (PI3-K), and p38 mitogen-activated protein kinase (MAPK) pathways
      (PD98059, LY294002, and SB203580, respectively), and then exposed to oxLDL for
      the uptake assay or oxLDL and [(3)H]-cholesterol and apolipoprotein A-I (apoA-I)
      for the cholesterol efflux assay. RESULTS: PTX3 overexpression not only promoted
      oxLDL uptake but also significantly reduced cholesterol efflux to apoA-I; it also
      significantly decreased the expression of peroxisome proliferator-activated
      receptor-gamma (PPARgamma), liver X receptor alpha (LXRalpha) and ATP-binding
      membrane cassette transporter A-1 (ABCA1), which was increased with PTX3
      silencing. Furthermore, PTX3 significantly increased p-ERK1/2 levels in THP-1
      derived foam cells, and inhibition of ERK1/2 by PD98059 significantly reduced the
      oxLDL uptake and promoted the cholesterol efflux induced by PTX3 overexpression.
      CONCLUSION: Here, we demonstrate that PTX3 affects lipid accumulation in human
      macrophages, increasing oxLDL uptake and inhibiting cholesterol efflux. That is
      the underlying possible mechanisms of PTX3 contribution to the progression of
      atherosclerosis.

PMID- 24675237
TI  - Charged nano-domes and bubbles in epitaxial graphene.
AB  - For the first time, new epitaxial graphene nano-structures resembling charged
      'bubbles' and 'domes' are reported. A strong influence, arising from the change
      in morphology, on the graphene layer's electronic, mechanical and optical
      properties has been shown. The morphological properties of these structures have
      been studied with atomic force microscopy (AFM), ultrasonic force microscopy
      (UFM) and Raman spectroscopy. After initial optical microscopy observation of the
      graphene, a detailed description of the surface morphology, via AFM and
      nanomechanical UFM measurements, was obtained. Here, graphene nano-structures,
      domes and bubbles, ranging from a few tens of nanometres (150-200 nm) to a few
      MUm in size have been identified. The AFM topographical and UFM stiffness data
      implied the freestanding nature of the graphene layer within the domes and
      bubbles, with heights on the order of 5-12 nm. Raman spectroscopy mappings of G
      and 2D bands and their ratio confirm not only the graphene composition of these
      structures but also the existence of step bunching, defect variations and the
      carrier density distribution. In particular, inside the bubbles and substrate
      there arises complex charge redistribution; in fact, the graphene bubble
      substrate interface forms a charged capacitance. We have determined the strength
      of the electric field inside the bubble-substrate interface, which may lead to a
      minigap of the order of 5 meV opening for epitaxial graphene grown on 4H-SiC face
      terminated carbon.

PMID- 24675238
TI  - Exploration of the impact of 'mild phenotypes' on median age at death in the U.K.
      CF registry.
AB  - BACKGROUND: The widespread availability of genetic testing allowing the
      identification of "milder" individuals with CF coincided with improvements in CF
      life expectancy but the relative contribution of case mix to that improved
      survival is uncertain. METHODS: Patients in the U.K. CF registry were divided
      into 'mild phenotype' defined as pancreatic sufficient and 'typical CF' defined
      as pancreatic insufficient. Distributions of age at death were compared with Mann
      Whitney test. Temporal trends in incidence and prevalence were described.
      Jonckheere-Terpstra test was used to compare the trend for median age at death
      from 2007 to 2010. RESULTS: Patients with 'mild phenotype' had significantly
      higher age at death (32 years, interquartile range 14 years versus 27 years,
      interquartile range 29 years; Mann-Whitney test p-value = 0.026). The proportion
      of patients with 'mild phenotype' appeared to be increasing (0.128 in 2007, 0.144
      in 2010). The trend for increasing age at death (from 25 years in 2007 to 29
      years in 2010, Jonckheere-Terpstra test p-value = 0.012) was independent of the
      'mild phenotype' patients. CONCLUSION: The impact of mild phenotypes on the
      improvement in the median age at death among people with CF was trivial.

PMID- 24675239
TI  - Understanding the GOLD 2011 Strategy as applied to a real-world COPD population.
AB  - STUDY OBJECTIVES: The aim of this analysis was to understand the implications of
      the GOLD 2011 multidimensional system for the assessment and management of COPD,
      using data from a real-world observational study. METHODS: Data were drawn from
      the Adelphi Respiratory Disease Specific Programme, a cross-sectional survey of
      consulting patients in five European countries and in the U.S. undertaken between
      June and September 2011. Patients were classified using both the GOLD 2010 and
      revised GOLD 2011 criteria, and profiled with regards to demographics, disease
      characteristics and treatment patterns. RESULTS: Information on 3813 COPD
      patients was collected. Disease characteristics showed a general tendency to
      worsen in parallel with worsening of symptoms. When comparing dual versus single
      risk criteria, the inclusion of exacerbation history resulted in an increase in
      the number of patients in high risk groups. The highest proportions of patients
      receiving inhaled corticosteroids (ICS) were in group D. However, a considerable
      proportion of patients in low risk groups were receiving ICS/long-acting beta2
      agonists. CONCLUSIONS: Our analysis confirmed the relationship between higher
      symptomatic burden, increased airflow limitation and exacerbation, and further
      illustrated the importance of including exacerbation history in the assessment of
      COPD to identify patients at high risk. As based on data from current clinical
      practice, this study also highlighted the frequent and potentially inappropriate
      use of ICS and bronchodilators in patients at low risk of experiencing
      exacerbations.

PMID- 24675240
TI  - Macromusophagy: A solo piano musical representation of macroautophagy.
AB  - Macroautophagy is a complex process involving dynamic membrane rearrangements in
      which parts of the cytoplasm are sequestered within double-membrane phagophores.
      Upon completion, these structures mature into autophagosomes that fuse with the
      yeast vacuole or mammalian lysosome, leading to degradation of the cargo and
      release of the resulting macromolecules back into the cytosol. How can the
      complexities of macroautophagy best be conveyed to an audience that is composed
      primarily of people who are not experts in this topic, and possibly not even
      scientists? The literature on learning is vast, and difficult to summarize, but
      there are certain themes that frequently appear. First, people learn in different
      ways. Thus, for example, while lectures are effective for conveying information
      to part of the audience, some will benefit tremendously from alternative methods
      of presentation. The latter can be visual (taking the form of illustrations,
      videos, or even physical movement), tactile or audible. Second, a line of
      research suggests that the engagement of more than one part of the brain (dual
      channels) improves learning. We decided to explore these concepts focusing on an
      audible format through a collaborative approach by combining a scientific
      explanation of macroautophagy with a musical score that was composed specifically
      to represent this process. 

PMID- 24675241
TI  - Single-port laparoscopic cholecystectomy versus the classical four port
      laparoscopic cholecystectomy: a randomized prospective clinical trial.
AB  - AIM: The objectives of this prospective study were to compare the advantages of
      single-port laparoscopic cholecystectomy (SPLC) versus the classical four-port
      laparoscopic cholecystectomy (CLC) and to discuss these advantages in the light
      of current literature. METHODS: Forty eligible patients were randomized to
      receive SPLC (Group A, N.=20) and CLC (Group B, N.=20), and investigated with
      regard to age, sex, BMI (body mass index), ASA (American Society of
      Anesthesiologists) score, type of surgery, operative time, per-operative
      complication, indication for conversion to open surgery, indication for
      additional trocar placement in SPLC technique, post-operative pain score,
      additional narcotic analgesic requirement, nausea and vomiting, post-operative
      complication and length of hospital stay. Visual analogue scale (VAS) was used
      for pain scoring in all cases. RESULTS: No significant difference was found among
      patients in Group A and Group B in terms of age, sex, weight/BMI, ASA score, VAS
      scores, additional analgesic requirement and length of hospital stay (P>0.05). On
      the other hand, mean operative time in Group A was significantly (P<0.005)
      greater than that in Group B. Mean operative time in Group A was observed to be
      reduced after the first 10 operations. Conversion to open surgery was not
      required in any of the patients; however, additional trocar placement was
      required in two patients in Group A due to body habitus and adhesions, and
      operations were completed laparoscopically. CONCLUSION: We conclude that SPLC is
      equally effective as CLC. Patient comfort is increased and pain is decreased as
      the surgeon gets experienced with the technique.

PMID- 24675242
TI  - Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive
      surgery and HIPEC.
AB  - AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally
      aggressive tumor with poor prognosis, related in most cases to asbestos exposure.
      It is increasing in frequency, but currently no standard therapy is available.
      The biology of this disease is still poorly understood. Several highly
      specialized centers have recently reported improved survival by means of an
      innovative local-regional approach. The purpose of this article is to evaluate
      the survival benefit and the morbidity rate of patients affected by DMPM treated
      at our institution by cytoreductive surgery (CRS) associated with hyperthermic
      intraperitoneal perioperative chemotherapy (HIPEC). METHODS: This study includes
      42 patients affected by DMPM treated by an uniform approach consisting of
      cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The
      primary end point was overall survival and morbidity rate. The secondary end
      point was evaluation of prognostic variables for overall survival. RESULTS: The
      median follow-up period was 72 months (range 1-235 months). Thirty-five patients
      (83.3%) presented epithelial tumors and 7 were affected by multicystic
      mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight
      patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate
      was 35.7% associated to a perioperative mortality of 7.1%. Median overall
      survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%,
      respectively. CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients
      is a feasible technique that allows to achieve encouraging results in terms of
      overall survival rate, with an acceptable morbidity rate. Further investigations
      are needed to clarify the role and the timing of this promising technique.

PMID- 24675243
TI  - Peritonectomy and hyperthermic chemotherapy in patients with advanced or
      recurrent ephitelial ovarian cancer: a single center cohort study.
AB  - AIM: The present study reports our experience concerning with the advanced cancer
      treatment (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy)
      in patients with advanced ovarian cancer ephitelial (AEOS) or recurrent ovarian
      cancer ephitelial (REOC). METHODS: In a period from October 2006 to December
      2009, we observed 25 patients affected by advanced ephitelial ovarian cancer or
      recurrent ephitelial ovarian cancer. All patients underwent CRS + HIPEC
      procedures. Peritoneal involvement was valued according to the Peritoneal Cancer
      Index (PCI) and the remaining postoperative disease according to the Completeness
      of Cytoreduction score (CC). HIPEC was always performed with closed technique for
      60 min, with an average inflow temperature of 42.5  degrees C. The drugs were
      administered in combination according two schemes: 1) cisplatin 60 mg/m2/L and
      caelyx 20 mg/m2/L; 2) 60 mg/m2/L taxotere and caelyx 20 mg/m2/L. Morbidity and
      mortality were evaluated in accordance with the NCI CTCAE v. 3.0 (USA). Finally,
      the Disease Free Survival and Overall Survival by the Kaplan-Meier method was
      rated. RESULTS: The average age observed was 64 years (range 46-76). Fourteen
      patients (56%) were affected by AEOC. From this group, 12 (48%) were subjected to
      neoadjuvant therapy and 2 (8%) to surgery as a first; 11 (44%) patients had REOC
      and all of them had previously undergone to surgery and adjuvant CHT. The average
      PCI was 12.63 (range 2-27). In 22 patients (88%), cytoreduction was considered
      total or almost total (CC-0 in 14 patients, CC-1 in 8); in 3 patients (12%), it
      had not been optimal (CC-2 or CC-3). In all 18 patients with PCI less than 15, it
      was possible to achieve an optimal cytoreduction, and this was possible only in 3
      of the 7 patients who had a PCI greater than 15. The average operative time,
      including HIPEC, was of 612 min (range 425 min-840 min). In 9 patients (36%), the
      postoperative course was uncomplicated, in 10 patients (40%) complications were
      minor (G1-G2) and in 4 patients (16%) morbidity was important (G4). Mortality
      rate was 8%. The average OS was 30.8 months and the median OS was 30.8 months
      (respectively 36.5 months for AEOC and 27 months for REOC). The median DFS total
      (calculated from the day of surgery or from the day of the beginning of the CHT)
      was 12months (respectively 12.9 months for AEOC, 11.9 months for REOC).
      CONCLUSION: Although the CRS and HIPEC procedure in the treatment of advanced or
      recurrent ovarian cancer represents now a reliable method with good results both
      in terms of morbidity and of distance results, there are still many controversial
      aspects that may in the future be better clarified only with a randomized phase
      III study, which is in progress, involving international working groups and
      experts on the procedure.

PMID- 24675244
TI  - Treatment of peritoneal carcinomatosis from ovarian cancer by surgical
      cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC).
AB  - AIM: Ovarian cancer may be considered as an "intraperitoneal disease" by itself.
      When surgical removal associated with systemic chemotherapy fails, usually, the
      history of the patients is characterized by poor prognosis. Some encouraging
      results have been reported by the treatment of peritoneal carcinomatosis (PC)
      from ovarian cancer by complete surgical cytoreduction, peritonectomy and
      hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this article
      was to evaluate the survival benefit and the morbidity of patients with ovarian
      cancer treated at our institution by cytoreductive surgery associated with
      hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: Between
      October 1995 and December 2012 more than 600 operations for PC were performed; in
      308 cases surgical cytoreduction associated with HIPEC was carried out. Eighty
      five patients treated by cytoreduction associated with HIPEC were affected by
      recurrent epithelial ovarian cancer (EOC). Statistical analysis was performed on
      70 patients (last 15 patients were too recent for evaluation). Two trials were
      applied: 1) patients presenting first peritoneal relapse after surgery and
      systemic chemotherapy (CT), 6 months later from last CT administration; 2)
      multiple relapse patients. RESULTS: On 70 patients, morbidity and mortality rates
      were 35.7% and 7.1%, respectively. Overall median survival was 42.0 months, but
      in primary EOC was 48.0 months and in recurrent EOC was 28 months (P=0.12).
      Statistical analysis revealed that the completeness of cytoreduction was the most
      statistically significant factor related to survival: in completely citoreduced
      patients, overall survival was 48 months. CONCLUSION: Citoreductive surgery
      associated to platinum compounds HIPEC is feasible and relatively safe in
      recurrent and primary PC from ovarian cancer. Better selection of patients and
      second-look surgery in high risk-patients have to be investigated to improve
      those encouraging results.

PMID- 24675245
TI  - Evaluating the efficacy of current treatments for reducing postoperative ileus: a
      randomized clinical trial in a single center.
AB  - AIM: Postoperative ileus has been considered an inevitable consequence of
      abdominal surgery. The aim of the study was to investigate the efficacy of same
      treatments in resolving postoperative ileus in various surgical approaches.
      METHODS: A total of 360 patients underwent abdominal surgery, and was divided
      into four groups: videolaparoscopic cholecystectomy, laparotomic colo-rectal
      surgery, laparotomic Hartmann procedure, laparotomic gastric surgery. In each
      group, patients received different postoperative treatments: chewing gum, olive
      oil, both, and water. Each group was compared with a control group. RESULTS: In
      patients who underwent videolaparoscopic cholecystectomy, median postoperative
      first passage of flatus and stool in the water group was 10 and 34 hours,
      respectively (P=0.006, P=0.021) and significantly earlier than in the control
      group (median postoperative 24 and 72 hours). Postoperative stay for the water
      group was lower (median day 1, 3rd interquartile 2.5) compared with control
      (median day 3; 3rd interquartile 7.0, P=0.01). In patients who underwent gastric
      surgery, median postoperative first passage of stool in the olive oil and chewing
      gum group was 48 hours, significantly earlier than in the control (median
      postoperative hour 120, P=0.04). Median time to first passage of flatus and stool
      was also earlier in the other groups compared with the control group, though this
      difference was not significant. CONCLUSION: Chewing gum, olive oil or both do not
      induce a relevant reduction of ileus after surgery. Water may be a safe and
      inexpensive option in reducing ileus. (United States National Institutes of
      Health, www.clinicaltrial.gov, number NCT01869231).

PMID- 24675246
TI  - Treatment of alcoholic very early hepatocellular carcinoma: role of percutaneous
      ablation. Beyond Barcellona criteria.

PMID- 24675247
TI  - Enough is enough.
AB  - Coinciding with the 50th anniversary of the first Surgeon General report on
      smoking and health (U.S. Department of Health, Education and Welfare, 1964) was
      the release of the 2014 Surgeon General report The Health Consequences of Smoking
      50 Years of Progress (U.S. Department of Health and Human Services, 2014). During
      a press conference announcing the report in January 2014, Acting Surgeon General
      Rear Admiral Boris Lushniak, MD, MPH, repeated the refrain "Enough is enough" in
      frustration with the continuing burden of death and misery caused by tobacco use
      as he urged action to be taken. That challenge gives us an opportunity to ask
      ourselves whether, as nurses (particularly as oncology nurses), we have done
      enough to help patients who are still struggling with nicotine addiction. 

PMID- 24675248
TI  - Navigation resources for survivorship.

PMID- 24675249
TI  - Management of dysphagia in patients with head and neck cancer.
AB  - Dysphagia is one of the most common symptoms affecting patients with head and
      neck cancer. It can lead to several complications and affect patients' quality of
      life. The advanced practice nurse can play an important role in the plan of care
      for managing this condition in patients with head and neck cancer. 

PMID- 24675250
TI  - Highly reliable health care in the context of oncology nursing: part I.
AB  - Oncology care is delivered under challenging circumstances. The principles of
      reliability science are used extensively in numerous high-risk and high-tech
      industries to improve quality and safety. This two-part series will discuss the
      concept of reliability science in the context of oncology nursing practice as a
      way to improve the quality and safety of care provided to patients with cancer. 

PMID- 24675251
TI  - The Iowa Model of Evidence-Based Practice to Promote Quality Care: an illustrated
      example in oncology nursing.
AB  - Evidence-based practice (EBP) improves the quality of patient care and helps
      control healthcare costs. Numerous EBP models exist to assist nurses and other
      healthcare providers to integrate best evidence into clinical practice. The Iowa
      Model of Evidence-Based Practice to Promote Quality Care is one model that should
      be considered. Using an actual clinical example, this article describes how the
      Iowa Model can be used effectively to implement an actual practice change at the
      unit or organizational level. 

PMID- 24675252
TI  - Safe management of chemotherapy in the home.

PMID- 24675253
TI  - Radiogenomics: the promise of personalized treatment in radiation oncology?
AB  - Significant variability exists in normal tissue reactions in patients with cancer
      receiving radiotherapy, with a subpopulation exhibiting increased toxicity to
      ionizing radiation. Genomic studies have proposed that single nucleotide
      polymorphisms in DNA repair genes, cytokines, and reactive oxygen species may
      play a role in clinical radiosensitivity. Additional research examining the
      association between genetic variants and radiation-induced inflammation and
      fibrosis may spur the development of targeted therapy in radiation oncology,
      which could increase cure rates and limit toxicity. As more people become long
      term cancer survivors, oncology nurses must aggressively assess and manage late
      treatment side effects to optimize patient functioning and quality of life. The
      purpose of the current article is to describe the effect of ionizing radiation on
      normal and irradiated tissue, discuss genetic mutations that are proposed to
      influence radiosensitivity, and identify future areas of research on the
      association between genetics and radiation toxicity. 

PMID- 24675254
TI  - Gastrointestinal nurse navigation: implementation of a novel role.
AB  - Gastrointestinal (GI) cancer is the second most frequent cancer diagnosis in the
      United States, and the care for patients with GI cancer is multifaceted, with
      each clinical encounter impacting patients' overall experience. Patients and
      families often navigate this complicated journey on their own with limited
      resources and knowledge; therefore, innovative, patient-centered, and quality
      focused programs must be developed. The purpose of this article is to discuss the
      development of GI nurse navigators (NNs) and the important role they have in
      providing coordinated evidence-based cancer care and in the benchmarking of
      quality metrics to allow more transparency and improve GI cancer care. This
      article provides a foundation for developing a GI NN role within the context of a
      newly developed multidisciplinary GI cancer program, and identifies the
      importance of tracking specific quality metrics. This innovative model is useful
      for healthcare organizations and nursing practice because it identifies the
      importance of a nurse in the navigator role, as well as highlights the numerous
      functions the NN can provide to the GI multidisciplinary team and patients. 

PMID- 24675255
TI  - Pain: a descriptive study in patients with cancer.
AB  - Ninety percent of patients with advanced cancer are reported to experience pain
      at some time during the course of their illness. This pain usually is improperly
      evaluated because it varies by patient and is difficult to control. Pain often
      cannot be conceptualized because of the individual nature of patient experience;
      however, patterns of pain occur in those suffering from similar conditions. This
      secondary analysis was conducted to examine the characteristics of pain in
      individuals with advanced cancer. The sample consisted of 717 patients with
      cancer who were receiving hospice home care in the southeastern United States. An
      understanding of the total pain experience, including type of pain and pain
      location, is important for addressing pain in patients with cancer in hospice
      care. More effective strategies are needed for pain management in this patient
      population. In addition, steps need to be taken to ensure that hospice care is
      understood by and made available to minorities. 

PMID- 24675256
TI  - Nursing burnout interventions: what is being done?
AB  - Many studies have documented high prevalence of burnout and compassion fatigue in
      oncology nurses. Burnout has detrimental effects on nurses, patients, and
      healthcare organizations. However, burnout interventions have been shown to
      improve the physical and mental health of nurses, patient satisfaction, and the
      organizational bottom line by reducing associated costs of burnout. Although
      treatment centers may prevent and correct burnout in oncology nurses by providing
      various interventions, few articles focus on those interventions. This article
      compiles and describes interventions that will serve as a reference to nurses and
      healthcare organization leaders interested in implementing similar programs. 

PMID- 24675257
TI  - Increasing certification through unit-based education.
AB  - Certification has been identified by multiple organizations as an important
      component and means of elevating the level of nursing care provided to patients
      and demonstrating to the public that the nursing staff has subspecialty
      knowledge. Certification may lead to improved patient satisfaction and outcomes
      as well as increased nurse satisfaction and retention. Despite the known
      potential benefits associated with certification, institutions struggle to
      improve certification rates. One possible method to overcome system barriers to
      certification is the implementation of a unit-based study course to prepare
      nurses for the Certified Breast Care Nurse (CBCN) examination. Data collected by
      an author-developed tool as one institution created and executed a unit-based
      study course suggest that such an approach increased certification rates and
      improved disease-specific knowledge and confidence among the staff, despite no
      official data existing on the tool's reliability and validity. Implementation of
      similar programs may be successful in improving certification at other
      institutions seeking to raise certification rates.

PMID- 24675258
TI  - Prevention and treatment of bone loss in patients with nonmetastatic breast or
      prostate cancer who receive hormonal ablation therapy.
AB  - Hormone ablation therapy is a mainstay in the treatment of breast and prostate
      cancers. However, aromatase inhibitors (AIs) used in postmenopausal women with
      breast cancer and androgen-deprivation therapy (ADT) used in men with prostate
      cancer contribute to substantial bone loss, thereby increasing the risk of
      osteoporotic fractures. Evidence-based guidelines, therefore, urge oncology
      practices to screen these patients for bone loss and, if needed, provide
      treatment to maintain bone health. In addition to lifestyle modification and
      calcium or vitamin D supplementation, bone protection strategies include
      treatment with bisphosphonates and denosumab, a monoclonal antibody against RANK
      ligand. Identification of patients at greater risk for bone loss and fracture and
      proper interventions can reduce fracture rates. Oncology nurses can play an
      important role in screening these patients. The purpose of this article is to
      inform oncology nurses about the effects of cancer treatment on bone health,
      review current prevention and treatment options for cancer treatment-induced bone
      loss, and discuss recommendations for identifying high-risk individuals. 

PMID- 24675260
TI  - Reevaluating the neutropenic diet: time to change.
AB  - The neutropenic diet historically has been a mainstay in oncology practice, with
      many providers continuing to adhere tightly to the diet for patients with
      neutropenia. However, clinically sound evidence remains limited and weak and does
      not support the diet as a foundation for policy and practice. Therefore, two
      questions remain: Does evidence exist to support the effectiveness of the
      neutropenic diet in reducing infection rates in the neutropenic oncology
      population? Based on limited evidence supporting the neutropenic diet in this
      population, what clinically sound diet strategies are best for these patients? 

PMID- 24675259
TI  - Evaluation of a breast and colon cancer survivorship program.
AB  - This article describes a cancer survivorship program that addressed quality of
      life (QOL) changes related to chemotherapy. The program focused on adult breast
      and colon cancer survivors at a community oncology practice in the southeastern
      United States, and consisted of an educational visit designed to identify and
      address QOL changes that occurred as a result of chemotherapy. The QOL of Cancer
      Survivors (QOL-CS) survey administered before and after the visit analyzed QOL
      metrics, which were combined with program evaluation data to assess physical,
      psychosocial, social, and spiritual well-being changes that may have occurred as
      a result of program participation. Differences in QOL-CS scores did not represent
      statistically significant changes in QOL for program participants. However,
      program evaluation responses identified perceived changes in QOL as a result of
      participating in cancer treatment and a subsequent cancer survivorship program,
      which demonstrated clinical significance for program participants. Physical,
      psychosocial, social, and spiritual well-being measures were affected by program
      participation. Improvement in distress related to the initial cancer diagnosis
      and family distress were the most significant reported changes, and male gender
      and advanced age were associated with improved psychosocial well-being. 

PMID- 24675261
TI  - Aspergillus pneumonia in adult patients with acute leukemia.
AB  - Aspergillus pneumonia often is a fatal consequence of prolonged neutropenia in
      patients with acute leukemia. Despite prompt diagnosis and adequate antifungal
      therapy, mortality remains high among these patients. Recognizing early signs and
      symptoms, as well as risk factors, is the key to reducing morbidity and
      mortality. 

PMID- 24675262
TI  - Care, compassion, and communication in professional nursing: art, science, or
      both.
AB  - Debate continues as to whether nursing is a science, art, or a combination of the
      two. Given the recent growing emphasis in the current healthcare environment to
      deliver patient-centered care, the art of nursing and its impact on patient
      outcomes is being re-examined. The current article discusses a case narrative to
      provide a venue for self-reflection in nursing practice. 

PMID- 24675264
TI  - The knowledge patients impart.

PMID- 24675265
TI  - Patient empowerment in the management of chronic myeloid leukemia.
AB  - Patient empowerment is a patient-centered approach to care in which healthcare
      providers nurture patients' innate abilities to self-manage and incorporate
      patient goals for therapy into the overall management plan. Standard care of
      chronic myeloid leukemia (CML) requires lifelong medication with oral therapy and
      regular follow-up. The success of CML treatment, therefore, depends on a high
      degree of patient involvement and motivation, as well as strong collaboration
      between patients and healthcare providers. Oncology nurses can support patients
      with CML from the time of diagnosis to the end of treatment to ensure they
      maintain high levels of involvement in their care. At the author's center,
      patients who most actively collaborate with their physicians in treatment
      decisions take personal responsibility for the quality of their care and show
      good adherence to treatment. In the current article, the author discusses the
      potential effect of patient response to cancer diagnosis on clinical outlook and
      describes strategies in place at the cancer center to ensure that patients
      diagnosed with CML have the best chance at keeping their cancer under control. 

PMID- 24675266
TI  - Adverse event management strategies: optimizing treatment with regorafenib in
      patients with metastatic colorectal cancer.
AB  - Patients with metastatic colorectal cancer (mCRC) frequently experience treatment
      related adverse events (AEs), which may lead to nonadherence or discontinuation
      from their treatment regimen. In the phase 3 CORRECT study, the addition of
      regorafenib to best supportive care (BSC) significantly increased overall
      survival and progression-free survival compared with placebo plus BSC in patients
      with mCRC who had progressed on all approved standard care therapies. Although
      regorafenib showed an acceptable safety profile, patients experienced treatment
      related AEs such as hand-foot skin reaction, hypertension, oral mucositis,
      diarrhea, fatigue, and liver abnormalities. The goal of this article is to help
      oncology nurses implement a strategic, proactive approach to AE management in
      patients mCRC treated with regorafenib. The article reviews the most common AEs
      associated with regorafenib in patients who participated in the CORRECT study and
      provides a strategy and practical measures that nurses can apply to AE
      management. In addition, the article provides direction and guidance for
      educating patients and their caregivers on recognizing and managing potential
      side effects of regorafenib. 

PMID- 24675267
TI  - Developing cancer-related educational content and goals tailored to the Comanche
      Nation.
AB  - Cancer-related educational content and goals should be modified to the needs of
      Native Americans to ensure adherence to healthy lifestyles. The current article
      describes the development of cancer-related educational modules that include
      creating behavioral goals specific to the people of the Comanche Nation. A
      community-based participatory research approach was used to conduct focus groups
      in the Comanche Nation and obtain feedback related to cancer-related educational
      modules and behavioral goals. Content analysis, verbatim transcriptions, field
      notes, and observations were used to analyze data and create five major themes.
      Comanche people need cancer educational modules and goals tailored to their
      culture to become engaged and maintain interest, thereby improving the likelihood
      of increasing cancer-related knowledge. Oncology nurses should respect guidance
      provided by Comanche community members to adapt cancer-related education
      materials and processes, as well as goal development, to address cultural
      concepts. When Comanche community members become knowledgeable and work toward
      healthy behavioral change, cancer health disparities may decrease. 

PMID- 24675268
TI  - Variations in self-reported nausea, vomiting, and well-being during the first 10
      days postchemotherapy in women with breast cancer.
AB  - Women with breast cancer undergoing chemotherapy experience nausea and vomiting,
      both common symptoms affecting quality of life. The aim of the current study was
      to describe how nausea, vomiting, and well-being vary during the first 10 days
      after chemotherapy in women with breast cancer. A pilot study with a repeated
      measurements design was conducted at a Swedish county hospital where 39 women
      with breast cancer treated with adjuvant chemotherapy were observed. A structured
      10-day diary was used for data collection. Of the 39 women in the study, 33
      experienced nausea and 6 also experienced vomiting after chemotherapy. Changes in
      well-being as a result of nausea or vomiting during any part of the day, as well
      as distress for other reasons, were reported. Well-being also varied among the
      individuals. The pattern of change in experienced levels of well-being was not
      homogeneous, nor did it move in any certain direction. The results of this study
      show that an individualized treatment approach is required to better meet
      individual women's needs. 

PMID- 24675269
TI  - Experimental testing and modeling analysis of solute mixing at water distribution
      pipe junctions.
AB  - Flow dynamics at a pipe junction controls particle trajectories, solute mixing
      and concentrations in downstream pipes. The effect can lead to different outcomes
      of water quality modeling and, hence, drinking water management in a distribution
      network. Here we have investigated solute mixing behavior in pipe junctions of
      five hydraulic types, for which flow distribution factors and analytical
      equations for network modeling are proposed. First, based on experiments, the
      degree of mixing at a cross is found to be a function of flow momentum ratio that
      defines a junction flow distribution pattern and the degree of departure from
      complete mixing. Corresponding analytical solutions are also validated using
      computational-fluid-dynamics (CFD) simulations. Second, the analytical mixing
      model is further extended to double-Tee junctions. Correspondingly the flow
      distribution factor is modified to account for hydraulic departure from a cross
      configuration. For a double-Tee(A) junction, CFD simulations show that the solute
      mixing depends on flow momentum ratio and connection pipe length, whereas the
      mixing at double-Tee(B) is well represented by two independent single-Tee
      junctions with a potential water stagnation zone in between. Notably, double-Tee
      junctions differ significantly from a cross in solute mixing and transport.
      However, it is noted that these pipe connections are widely, but incorrectly,
      simplified as cross junctions of assumed complete solute mixing in network
      skeletonization and water quality modeling. For the studied pipe junction types,
      analytical solutions are proposed to characterize the incomplete mixing and hence
      may allow better water quality simulation in a distribution network. 

PMID- 24675270
TI  - Hydroxyl radical (OH) scavenging in young and mature landfill leachates.
AB  - The final discharge point for collected landfill leachates is frequently the
      local municipal wastewater treatment facility. The salinity, color, nutrient, and
      anthropogenic organics contamination of leachates often necessitate some form of
      pre-treatment. When advanced oxidation processes (AOPs) are considered for pre
      treatment, the unique composition of dissolved organic matter (DOM) and the
      relatively high concentrations of some inorganic solutes in leachate will inhibit
      treatment efficiency. The most important benchmark for design of AOPs is the
      expected steady-state production of free radical (OH). Without a quantitative
      assessment of total OH consumption in high-strength waste water, like a landfill
      leachate, efficient AOP treatment is uncertain. For this reason, two landfill
      leachates, distinct in color, DOM, and age of landfill, were characterized for OH
      scavenging using an established competition kinetics method. After stripping the
      samples of inorganic carbon, the DOM in leachate from mature (stabilized)
      landfill was found to react with OH at a rate of 9.76 * 10(8) M(-1)s(-1).
      However, DOM in leachate from newer landfill was observed to scavenge available
      OH at a faster rate (8.28 * 10(9) M(-1)s(-1)). The combination of fast rate of
      reaction with OH and abundance of DOM in the sampled leachate severely limited
      the contribution of OH to degradation of an O3- and OH-labile organic probe
      compound (bisphenol-a) in oxidized mature leachate (fOH = 0.03). Substantial
      dosing of both O3 and H2O2 (>70 mg/L and >24 mg/L, respectively) may be required
      to see at least 1-log-removal (>90%) of an OH-selective leachate contaminant
      (i.e., parachlorobenzoic acid) in a mature landfill leachate. 

PMID- 24675271
TI  - Rheological characterisation of thermally-treated anaerobic digested sludge:
      impact of temperature and thermal history.
AB  - This study investigated the partially irreversible effect of thermal treatment on
      the rheology of digested sludge when it was subjected to temperature change
      between 20  degrees C and 80  degrees C and then cooled down to 20  degrees C.
      The yield stress, infinite viscosity and liquor viscosity of sludge were measured
      at 20  degrees C for different thermal histories and were compared to the
      evolution of the solubilised chemical oxygen demand (COD) of sludge liquor. The
      results showed that thermal history irreversibly affects sludge rheology as the
      yield stress of sludge which was heated to 80  degrees C then cooled down to 20 
      degrees C was 68% lower than the initial yield stress at 20  degrees C. This
      decrease was due to the irreversible solubilisation of solid matter during
      heating as underlined by soluble COD data which did not reach its original level
      after thermal treatment. Measured soluble COD of sludge which was heated and
      cooled down was much higher than the soluble COD of initial sludge. We found a
      proportionality of the increase of soluble COD with the decrease of the yield
      stress as well as increase of infinite viscosity. 

PMID- 24675272
TI  - Linkages between microbial functional potential and wastewater constituents in
      large-scale membrane bioreactors for municipal wastewater treatment.
AB  - Large-scale membrane bioreactors (MBRs) have been widely used for the municipal
      wastewater treatment, whose performance relies on microbial communities of
      activated sludge. Nevertheless, microbial functional structures in MBRs remain
      little understood. To gain insight into functional genes and their steering
      environmental factors, we adopted GeoChip, a high-throughput microarray-based
      tool, to examine microbial genes in four large-scale, in-operation MBRs located
      in Beijing, China. The results revealed substantial microbial gene heterogeneity
      (43.7-85.1% overlaps) among different MBRs. Mantel tests indicated that microbial
      nutrient cycling genes were significantly (P < 0.05) correlated to influent COD,
      [Formula: see text] -N, TP or sulfate, which signified the importance of
      microbial mediation of wastewater constituent removal. In addition, functional
      genes shared by all four MBRs contained a large number of genes involved in
      antibiotics resistance, metal resistance and organic remediation, suggesting that
      they were required for degradation or resistance to toxic compounds in
      wastewater. The linkages between microbial functional structures and
      environmental variables were also unveiled by the finding of hydraulic retention
      time, influent COD, [Formula: see text] -N, mixed liquid temperature and humic
      substances as major factors shaping microbial communities. Together, the results
      presented demonstrate the utility of GeoChip-based microarray approach in
      examining microbial communities of wastewater treatment plants and provide
      insights into the forces driving important processes of element cycling. 

PMID- 24675273
TI  - Evaluation of DNA damage reversal during medium-pressure UV disinfection.
AB  - Ultraviolet (UV) disinfection relies on the principal that DNA exposure to UV
      irradiation leads to the formation of cytotoxic lesions resulting in the
      inactivation of microorganisms. Cyclobutane pyrimdine dimers (CPDs) account for
      the majority of DNA lesions upon UV exposure. Past research has demonstrated
      reversal of CPDs in extracted DNA formed at high UV-C wavelength irradiation (280
      nm) upon subsequent irradiation at lower UVC wavelengths (230-240 nm). Medium
      pressure (MP) UV lamps produce a polychromatic emission giving rise to the
      possibility that cellular DNA in a target pathogen may undergo simultaneous
      damage and repair when exposed to multiple wavelengths during the disinfection
      process, decreasing the efficiency of MP UV lamp disinfection. Culture techniques
      and a quantitative polymerase chain reaction (qPCR) assay were used to examine
      cell viability and DNA damage reversal. qPCR results indicated direct
      photoreversal of UV-induced DNA damage through sequential irradiations of 280 nm
      followed by 228 nm in Escherichia coli DNA. However, significant photoreversal
      was only observed after high initial doses and secondary doses of UV light. The
      doses where significant photoreversal took place were more than 10 times higher
      than those typically used in UV disinfection. Despite evidence of CPD
      photoreversal, bacterial growth assays showed no indication that sequential
      wavelength irradiations result in higher survival rates than single-wavelength
      irradiations. 

PMID- 24675274
TI  - On the nucleotide composition and structure of retroviral RNA genomes.
AB  - Retroviral RNA genomes display a rich variety in their nucleotide composition.
      For instance, the single-stranded RNA genome of human T cell leukemia virus (HTLV
      1) is C-rich and G-poor and that of the human immunodeficiency virus (HIV-1) is A
      rich and C-poor. Animal retroviruses add further variation to this unexplained,
      but many times remarkable virus-specific property. We previously described that
      the nucleotide bias is even more extreme in the unpaired regions of the
      structured HIV-1 RNA genome, which has been probed by SHAPE technology. We now
      document that the same trend is apparent for the MFold-predicted RNA structure of
      HIV-1 RNA and subsequently investigated the predicted structures of the RNA
      genomes of other retroviruses. We conclude that all virus-specific signatures are
      enhanced for the unpaired nucleotides in the RNA genome. Consequently, the
      differences in nucleotide count between the diverse human and animal retroviruses
      are further exposed in the single stranded genome regions. We used a skew
      analysis to visualize these striking differences in nucleotide usage.
      Evolutionary events responsible for these nucleotide signatures will be
      discussed. 

PMID- 24675275
TI  - Molecular mechanisms enhancing the proteome of influenza A viruses: an overview
      of recently discovered proteins.
AB  - Influenza A virus is one of the major human pathogens. Despite numerous efforts
      to produce absolutely effective anti-influenza drugs or vaccines, no such agent
      has been developed yet. One of the main reasons for this complication is the high
      mutation rate and the specific structure of influenza A viruses genome. For more
      than 25 years since the first mapping of the viral genome, it was believed that
      its 8 genome segments encode 10 proteins. However, the proteome of influenza A
      viruses has turned out to be much more complex than previously thought. In 2001,
      the first accessory protein, PB1-F2, translated from the alternative open reading
      frame, was discovered. Subsequently, six more proteins, PB1-N40, PA-X, PA-N155,
      PA-N182, M42, and NS3, have been found. It is important to pay close attention to
      these novel proteins in order to evaluate their role in the pathogenesis of
      influenza, especially in the case of outbreaks of human infections with new avian
      viruses, such as H5N1 or H7N9. In this review we summarize the data on the
      molecular mechanisms used by influenza A viruses to expand their proteome and on
      the possible functions of the recently discovered viral proteins. 

PMID- 24675276
TI  - The structural and phylogenetic profile of the 3' terminus of coxsackievirus B3
      negative strand.
AB  - In the replication process of RNA(+) viruses both the positive-strand template
      and the newly synthesized negative strand appear in a double-stranded form, RF.
      It has been shown for poliovirus that prior to the initiation of positive-strand
      synthesis, the 5'-terminus of the positive strand must adopt a cloverleaf
      structure. When that happens, the 3'-terminal region of the negative strand is
      released from the RF form and is able to form into its own defined structure. In
      order to determine the secondary structure of this region, a comprehensive
      approach consisting of experimental mapping methods, phylogenetic analysis and
      computer predictions was applied. Here we propose the first structural model of
      the 3'-terminal region of the coxsackievirus B3 (CV-B3) negative strand,
      approximately 450 nucleotides in length. The region folds into three highly
      defined structural domains, I'-III'. The most 3'-terminal part of this region is
      domain I', which folds into a cloverleaf structure similar to that found in the
      viral RNA strand of positive-polarity. Remarkably, this motif is conserved among
      all analyzed viral isolates of CV-B3 despite the observed sequence diversity.
      Several other conserved structural motifs within the 3'-terminal region of the
      viral negative strand were also identified. The structure of this region may be
      crucial for the replication complex assembly.

PMID- 24675277
TI  - An in vitro study on the interaction of hydroxyapatite nanoparticles and bone
      marrow mesenchymal stem cells for assessing the toxicological behaviour.
AB  - Mesenchymal stem cells or multipotent progenitor cells isolated from bone marrow
      presents close resemblance to the natural in vivo milieu and hence preferred more
      than the conventional cell culture systems to predict the toxicological behavior
      of bio-nano interaction. The objective of the present study is to evaluate the
      molecular toxicity of hydroxyapatite nanoparticles (HANPs) using mouse bone
      marrow mesenchymal stem cells (BMSCs). In-house synthesized HANPs (50 nm) were
      used to study the cytotoxicity, nano particle uptake, effect on cyto skeletal
      arrangement, oxidative stress response and apoptotic behavior with the confluent
      BMSCs as per standard protocols. The results of the MTT assay indicated that
      HANPs does not induce cytotoxicity up to 800 MUg/mL. It was also observed that
      oxidative stress related apoptosis and reactive oxygen species (ROS) production
      following nanoparticle treatment was similar to that of control (cells without
      treatment). Hence it can be concluded that the in-house synthesized HANPs are non
      toxic/safe at the molecular level suggesting that the HANPs are compatible to
      BMSCs. Further, the in vitro BMSCs cell culture can be used as a model for
      evaluating the preliminary toxicity of nanomaterials.

PMID- 24675278
TI  - Effects of genipin cross-linking of chitosan hydrogels on cellular adhesion and
      viability.
AB  - PURPOSE: The aim of the present study was to investigate the effects of genipin
      (Gp) cross-linking of chitosan (CHI) hydrogels on the cell adhesion and
      viability. METHOD: Series of Gp crosslinked CHI hydrogels were prepared by
      incubation of solutions containing a mixture of Gp and CHI in different ratios.
      The resulting hydrogels were characterized by scanning electron microscopy (SEM),
      parallel plate rheometer, contact angle and swelling ratio measurement. The in
      vitro cytocompatibility of hydrogels was evaluated with L929 fibroblasts by MTT
      method. The cell adhesion morphology on gel surface was characterized by SEM, and
      the cell viability was assessed through cell count and flow cytometry analysis.
      RESULTS: It was found that macroporous structure of the CHI hydrogels could be
      tailored by varying Gp or CHI amount. Gp cross-linking of hydrogels enhanced
      their storage modulus significantly, and also altered their hydrophilicity and
      swell properties. The MTT results revealed that the cross-linked hydrogels did
      not induce cytotoxic effects. Cell count and flow cytometry analysis demonstrated
      that denser surface milieu of hydrogels could facilitate better cell adhesion and
      viability. CONCLUSIONS: It could be concluded that increased cross-linking
      density significantly improved the cell adhesion and viability on hydrogel
      surface. This research provides prospective biocompatible approaches by making
      gel stiffness modifications to hydrogel scaffolds for the purpose of different
      tissue engineering.

PMID- 24675279
TI  - Doxorubicin-conjugated core-shell magnetite nanoparticles as dual-targeting
      carriers for anticancer drug delivery.
AB  - The present study reports the successful synthesis of core-shell nanostructures
      composed of magnetite nanoparticles (Fe3O4-NPs) conjugated to the anticancer drug
      doxorubicin, intended for dual targeting of the drug to the tumor sites via a
      combination of the magnetic attraction and the pH-sensitive cleavage of the drug
      particle linkages along with a longer circulation time and reduced side effects.
      To improve the carrier biocompatibility, the prepared nanocarrier was, finally
      coated by chitosan. FT-IR analysis confirmed the synthesis of functionalized
      Fe3O4-NPs, doxorubicin-conjugated Fe3O4-NPs, and chitosan-coated nanocarriers.
      Scanning electron microscopy (SEM) indicated the formation of spherical
      nanostructures with the final average particle size of around 50 nm. The
      vibrating sample magnetometer (VSM) analysis showed that the saturation
      magnetization value (Ms) of carrier was 6 emu/g. The drug release behavior from
      the nanocarriers was investigated both in acidic and neutral buffered solutions
      (pH values of 5.3 and 7.4, respectively) and showed two-fold increase in the
      extent of drug release at pH 5.3 compared to pH 7.4 during 7 days. The results
      showed that the dual-targeting nanocarriers responded successfully to the
      external magnetic field and pH. From the results obtained, it can be concluded
      that this methodology can be used to target and improve therapeutic efficacy of
      the anticancer drugs.

PMID- 24675280
TI  - Implementation of sustainable evidence-based practice for the assessment and
      management of pain in residential aged care facilities.
AB  - Pain is common in residential aged care facilities (RACFs). In 2005, the
      Australian Pain Society developed 27 recommendations for good practice in the
      identification, assessment, and management of pain in these settings. This study
      aimed to address implementation of the standards and evaluate outcomes. Five
      facilities in Australia participated in a comprehensive evaluation of RACF pain
      practice and outcomes. Pre-existing pain management practices were compared with
      the 27 recommendations, before an evidence-based pain management program was
      introduced that included training and education for staff and revised in-house
      pain-management procedures. Post-implementation audits evaluated the program's
      success. Aged care staff teams also were assessed on their reports of self
      efficacy in pain management. The results show that before the implementation
      program, the RACFs demonstrated full compliance on 6 to 12 standards. By the
      project's completion, RACFs demonstrated full compliance with 10 to 23 standards
      and major improvements toward compliance in the remaining standards. After
      implementation, the staff also reported better understanding of the standards (p
      < .001) or of facility pain management guidelines (p < .001), increased
      confidence in therapies for pain management (p < .001), and increased confidence
      in their training to assess pain (p < .001) and recognize pain in residents with
      dementia who are nonverbal (p = .003). The results show that improved evidence
      based practice in RACFs can be achieved with appropriate training and education.
      Investing resources in the aged care workforce via this implementation program
      has shown improvements in staff self-efficacy and practice. 

PMID- 24675281
TI  - Development and validation of an observation tool for the assessment of nursing
      pain management practices in intensive care unit in a standardized clinical
      simulation setting.
AB  - Pain management in the intensive care unit is often inadequate. There is no tool
      available to assess nursing pain management practices. The aim of this study was
      to develop and validate a measuring tool to assess nursing pain management in the
      intensive care unit during standardized clinical simulation. A literature review
      was performed to identify relevant components demonstrating optimal pain
      management in adult intensive care units and to integrate them in an observation
      tool. This tool was submitted to an expert panel and pretested. It was then used
      to assess pain management practice during 26 discrete standardized clinical
      simulation sessions with intensive care nurses. The Nursing Observation Tool for
      Pain Management (NOTPaM) contains 28 statements grouped into 8 categories, which
      are grouped into 4 dimensions: subjective assessment, objective assessment,
      interventions, and reassessment. The tool's internal consistency was calculated
      at a Cronbach's alpha of 0.436 for the whole tool; the alpha varies from 0.328 to
      0.518 for each dimension. To evaluate the inter-rater reliability, intra-class
      correlation coefficient was used, which was calculated at 0.751 (p < .001) for
      the whole tool, with variations from 0.619 to 0.920 (p < .01) between dimensions.
      The expert panel was satisfied with the content and face validity of the tool.
      The psychometric qualities of the NOTPaM developed in this study are
      satisfactory. However, the tool could be improved with slight modifications.
      Nevertheless, it was useful in assessing intensive care nurses' pain management
      in a standardized clinical simulation. The NOTPaM is the first tool created for
      this purpose. 

PMID- 24675283
TI  - Graphene-boron nitride superlattices: the role of point defects at the BN layer.
AB  - We investigate, by means of first-principles calculations, the role of hBN point
      defects on the energetical stability and electronic structure of heterostructures
      composed of graphene atop hBN, rotated at angles of 13.17 degrees , 9.43 degrees 
      and 7.34 degrees . We consider, as possible point defects, boron and nitrogen
      vacancies and antisites, substitutional oxygen at the nitrogen site ON,
      substitutional carbon dimers, and nitrogen interstitials. The electronic and
      structural properties of all defects were analyzed. Among these, the most stable
      is ON, with negative formation energies at several possible rotation angles and
      chemical environments. Under such conditions, ON doping can raise the Fermi level
      of the neutral system by as much as 1 eV relative to graphene's Dirac point,
      reaching the band crossing between adjacent Dirac cones at the M point of the
      heterostructure Brillouin zone. This could lead to interesting electronic
      transport properties without the need for electrostatic doping.

PMID- 24675282
TI  - Mitochondrial DNA disease-molecular insights and potential routes to a cure.
AB  - Mitochondrial DNA diseases are common neurological conditions caused by mutations
      in the mitochondrial genome or nuclear genes responsible for its maintenance.
      Current treatments for these disorders are focussed on the management of the
      symptoms, rather than the correction of biochemical defects caused by the
      mutation. This review focuses on the molecular effects of mutations, the symptoms
      they cause and current work focusing on the development of targeted treatments
      for mitochondrial DNA disease. 

PMID- 24675285
TI  - Our advances are fabulous. Then what is the problem?

PMID- 24675284
TI  - Epigenetics: a new way to look at kidney diseases.
AB  - Only a few percent of the 3 billion pairs of chemical letters in the human genome
      is responsible for protein-coding sequences. Recent advances in the field of
      epigenomics have helped us to understand how most of the remaining sequences are
      responsible for gene regulation at baseline and in disease conditions. Here we
      discuss recent advances in the area of epigenetics--specifically in cytosine
      modifications--and its application in the field of nephrology.

PMID- 24675286
TI  - Comment on Smithson et al.'s review of stimulant medication usage to improve
      neurocognitive and learning outcomes in childhood brain tumour survivors.

PMID- 24675288
TI  - Social inequality in motorcycle helmet use: when a reduction in inequality is not
      necessarily good news.
AB  - BACKGROUND: We sought to examine changes in the magnitude of social inequality in
      motorcycle helmet use in Taiwan between 2001 and 2009. METHODS: Using data from
      the 2001 and 2009 Taiwan National Health Interview Surveys, we calculated
      absolute (the slope index of inequality, SII) and relative (relative index of
      inequality, RII) measures of inequality in helmet use by three indicators of
      socioeconomic position. RESULTS: The rate of motorcycle helmet use was 92% (14
      801/16 100) in 2001 and decreased to 89% (15 748/17 948) in 2009. We noted a
      significant decrease in social inequality in helmet use in RII according to
      urbanisation level, a significant decrease in SII and RII according to income
      level, and a significant increase in SII according to education level. The
      reduction in RII according to urbanisation level was more prominent than that
      based on income level, from 1.73 (95% CI 1.63 to 1.84) in 2001 to 1.33 (95% CI
      1.27 to 1.39) in 2009. The decline in helmet use was most prominent for
      motorcycle users who live in suburban areas, from 94% in 2001 to 88% in 2009.
      CONCLUSIONS: The significant reduction of social inequality in helmet use
      according to urbanisation level and income is not a public health success story.
      Rather, it is a warning sign of slackening law enforcement in Taiwan.

PMID- 24675287
TI  - Estrogen receptor, Progesterone receptor, HER2 status and Ki67 index and
      responsiveness to adjuvant tamoxifen in postmenopausal high-risk breast cancer
      patients enrolled in the DBCG 77C trial.
AB  - BACKGROUND: The DBCG 77C trial compared one year of tamoxifen in postmenopausal,
      steroid-receptor unknown, high-risk breast cancer patients to no adjuvant
      systemic therapy. After a potential follow-up of 30years we report overall
      efficacy of the study and results according to subtypes subsequently assessed by
      immunohistochemistry and fluorescent in situ hybridisation (FISH). METHODS:
      Between 1977 and 1982, 1716 postmenopausal patients with tumours larger than 5cm
      or positive axillary nodes were randomly assigned to no systemic therapy or
      tamoxifen 30mg daily for one year. Archival tumour tissue from 1515 patients was
      analysed and the hormone receptor positive (estrogen receptor (ER) and/or
      progesterone receptor (PR)) cancers were defined as luminal A if Ki67 low and
      HER2-negative; as luminal B if Ki67 high or HER2-positive; and otherwise as non
      luminal-HER2 positive or triple negative. FINDINGS: In the intent-to-treat (ITT)
      population one year of tamoxifen improved the disease-free-survival (DFS) (hazard
      ratio (HR)=0.87; 95% confidence interval (CI) 0.77-0.98), the Breast Cancer
      Recurrence Rate (BCRR) (HR=0.79; 0.69-0.90) and reduced the breast-cancer
      specific-mortality (BCM) (HR=0.83; 0.73-0.93). BCRR were improved significantly
      by tamoxifen in luminal A (HR=0.66; 0.53-0.84) and luminal B/HER2- (HR=0.54; 0.39
      0.74) but not in the other subsets, and with similar results for BCM with 30years
      follow-up. INTERPRETATION: One year of treatment with tamoxifen significantly
      improves BCRR and BCM in postmenopausal patients with ER positive breast cancers.
      The relative benefit from tamoxifen was not significantly different in luminal A
      and B subtypes. FUNDING: The Danish Breast Cancer Cooperative Group (DBCG)
      prepared the original protocol (DBCG 77C) and was the sponsor of the study.
      Funding was not provided to the participating departments. The biomarker study
      was supported by grants from the Clinical Institute, Odense University.

PMID- 24675289
TI  - Trends in cardiovascular risk factors across levels of education in a general
      population: is the educational gap increasing? The Tromso study 1994-2008.
AB  - BACKGROUND: To describe trends in cardiovascular risk factors and change over
      time across education levels, and study the influence from medicine use and
      gender. METHODS: Data from participants (30-74 years) of the Tromso Study in 1994
      1995 (n=22 108) and in 2007-2008 (n=11 565). Blood samples, measurements and self
      reported educational level and medicine use were collected. RESULTS: Differences
      in risk factor levels across education groups were persistent for all risk
      factors over time, with a more unfavourable pattern in the lowest education
      group. The exception was cholesterol, with the reduction being largest in the
      lowest educated, resulting in weakened educational trends over time. While a
      significant educational trend in cholesterol persisted among the non-users of
      lipid-lowering drugs (LLD), no educational trend in cholesterol was found among
      the LLD users in 2007-2008. The strongest educational trends were found for daily
      smoking and Body Mass Index (BMI). In 2007-2008 the odds for being a smoker were
      five times higher among the lowest educated compared to the highest educated. In
      men, the odds for being in the highest quintile of the BMI distribution were, in
      2007-2008, almost doubled in the lowest compared to the highest educated. The
      lowest educated women had 6.2 mm Hg higher mean systolic blood pressure than the
      highly educated, mean BMI of 26.4 kg/m 2 and smoking prevalence of 37.7%.
      CONCLUSIONS: The difference across education groups for cholesterol levels
      decreased, while the educational gap persisted over time for the other risk
      factors. Use of LLD seemed to contribute to the reduction of social differences
      in cholesterol levels.

PMID- 24675291
TI  - Metabolic efficiency underpins performance trade-offs in growth of Arabidopsis
      thaliana.
AB  - Growth often involves a trade-off between the performance of contending tasks;
      metabolic plasticity can play an important role. Here we grow 97 Arabidopsis
      thaliana accessions in three conditions with a differing supply of carbon and
      nitrogen and identify a trade-off between two tasks required for rosette growth:
      increasing the physical size and increasing the protein concentration. We employ
      the Pareto performance frontier concept to rank accessions based on their
      multitask performance; only a few accessions achieve a good trade-off under all
      three growth conditions. We determine metabolic efficiency in each accession and
      condition by using metabolite levels and activities of enzymes involved in growth
      and protein synthesis. We demonstrate that accessions with high metabolic
      efficiency lie closer to the performance frontier and show increased metabolic
      plasticity. We illustrate how public domain data can be used to search for
      additional contending tasks, which may underlie the sub-optimality in some
      accessions. 

PMID- 24675292
TI  - Abstracts of the American Association of Plastic Surgeons 93rd Annual Meeting,
      April 5-8, 2014, Miami, FL.

PMID- 24675290
TI  - Heat shock proteins in multiple myeloma.
AB  - Heat shock proteins are molecular chaperones with a central role in protein
      folding and cellular protein homeostasis. They also play major roles in the
      development of cancer and in recent years have emerged as promising therapeutic
      targets. In this review, we discuss the known molecular mechanisms of various
      heat shock protein families and their involvement in cancer and in particular,
      multiple myeloma. In addition, we address the current progress and challenges in
      pharmacologically targeting these proteins as anti-cancer therapeutic strategies.

PMID- 24675358
TI  - Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma.
AB  - Pleuropulmonary blastoma (PPB) is a rare pediatric malignancy whose pathogens are
      poorly understood. Recent reports suggest that germline mutations in the microRNA
      processing enzyme DICER1 may contribute to PPB development. To investigate the
      genetic basis of this cancer, we performed whole-exome sequencing or targeted
      deep sequencing of multiple cases of PPB. We found biallelic DICER1 mutations to
      be very common, more common than TP53 mutations also found in many tumors.
      Somatic ribonuclease III (RNase IIIb) domain mutations were identified in all
      evaluable cases, either in the presence or absence of nonsense/frameshift
      mutations. Most cases had mutated DICER1 alleles in the germline with or without
      an additional somatic mutation in the remaining allele, whereas other cases
      displayed somatic mutations exclusively where the RNase IIIb domain was
      invariably affected. Our results highlight the role of RNase IIIb domain
      mutations in DICER1 along with TP53 inactivation in PPB pathogenesis.

PMID- 24675359
TI  - Transient antiangiogenic treatment improves delivery of cytotoxic compounds and
      therapeutic outcome in lung cancer.
AB  - Extensive oncologic experience argues that the most efficacious applications of
      antiangiogenic agents rely upon a combination with cytotoxic drugs. Yet there
      remains a lack of clarity about how to optimize scheduling for such drug
      combinations. Prudent antiangiogenic therapy might transiently normalize blood
      vessels to improve tumor oxygenation and drug exposure. Using [(15)O]H2O positron
      emission tomography imaging in a preclinical mouse model of non-small cell lung
      cancer, we observed that short-term treatment with the vascular endothelial
      growth factor receptor/platelet-derived growth factor receptor inhibitor PTK787
      licensed a transient window of improved tumor blood flow. The improvement
      observed was associated with a reduced leakiness from tumor vessels, consistent
      with induction of a vascular normalization process. Initiation of a cytotoxic
      treatment in this window of tumor vessel normalization resulted in increased
      efficacy, as illustrated by improved outcomes of erlotinib administration after
      initial PTK787 treatment. Notably, intermittent PTK787 treatment also facilitated
      long-term tumor regression. In summary, our findings offer strong evidence that
      short-term antiangiogenic therapy can promote a transient vessel normalization
      process that improves the delivery and efficacy of a targeted cytotoxic drug.

PMID- 24675360
TI  - BCR-ABL-induced deregulation of the IL-33/ST2 pathway in CD34+ progenitors from
      chronic myeloid leukemia patients.
AB  - Although it is generally acknowledged that cytokines regulate normal
      hematopoiesis in an autocrine/paracrine fashion, their possible role in chronic
      myelogenous leukemia (CML) and resistance to imatinib mesylate treatment remain
      poorly investigated. Here, we report that CD34(+) progenitors from patients with
      CML at diagnosis are selectively targeted by the cytokine/alarmin interleukin
      (IL)-33. Indeed, CML CD34(+) progenitors upregulate their cell surface expression
      of the IL-33-specific receptor chain ST2, proliferate and produce cytokines in
      response to IL-33, conversely to CD34(+) cells from healthy individuals.
      Moreover, ST2 overexpression is normalized following imatinib mesylate therapy,
      whereas IL-33 counteracts in vitro imatinib mesylate-induced growth arrest in CML
      CD34(+) progenitors via reactivation of the STAT5 pathway, thus supporting the
      notion that IL-33 may impede the antiproliferative effects of imatinib mesylate
      on CD34(+) progenitors in CML. Clinically, the levels of circulating soluble ST2,
      commonly considered a functional signature of IL-33 signaling in vivo, correlate
      with disease burden. Indeed, these elevated peripheral concentrations associated
      with a high Sokal score predictive of therapeutic outcome are normalized in
      patients in molecular remission. Finally, we evidenced a facilitating effect of
      IL-33 on in vivo maintenance of CD34(+) progenitors from patients with CML by
      using xenotransplant experiments in immunodeficient NOG mice, and we showed that
      engraftment of mouse BCR-ABL-transfected bone marrow progenitors was less
      efficient in IL-33-deficient mice compared with wild-type recipients. Taken
      together, our results provide evidence that IL-33/ST2 signaling may represent a
      novel cytokine-mediated mechanism contributing to CML progenitor growth and
      support a role for this pathway in CML maintenance and imatinib mesylate
      resistance.

PMID- 24675362
TI  - Visualization of channels connecting cells in filamentous nitrogen-fixing
      cyanobacteria.
AB  - Cyanobacteria, formerly called blue-green algae, are abundant bacteria that carry
      out green plant photosynthesis, fixing CO2 and generating O2. Many species can
      also fix N2 when reduced nitrogen sources are scarce. Many studies imply the
      existence of intracellular communicating channels in filamentous cyanobacteria,
      in particular, the nitrogen-fixing species. In a species such as Anabaena, growth
      in nitrogen-depleted medium, in which ~10% of the cells differentiate into
      anaerobic factories for nitrogen fixation (heterocysts), requires the transport
      of amino acids from heterocysts to vegetative cells, and reciprocally, the
      transport of sugar from vegetative cells to heterocysts. Convincing physical
      evidence for such channels has been slim. Using improved preservation of
      structure by high-pressure rapid freezing of samples for electron microscopy,
      coupled with high-resolution 3D tomography, it has been possible to visualize and
      measure the dimensions of channels that breach the peptidoglycan between
      vegetative cells and between heterocysts and vegetative cells. The channels
      appear to be straight tubes, 21 nm long and 14 nm in diameter for the latter and
      12 nm long and 12 nm in diameter for the former.-Omairi-Nasser, A., Haselkorn,
      R., Austin, J. II. Visualization of channels connecting cells in filamentous
      nitrogen-fixing cyanobacteria. 

PMID- 24675361
TI  - Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy
      of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers.
AB  - Although several groups have demonstrated that concomitant use of MEK and
      phosphoinositide 3-kinase (PI3K) inhibitors (MEKi/PI3Ki) can induce dramatic
      tumor regressions in mouse models of KRAS-mutant non-small cell lung cancer
      (NSCLC), ongoing clinical trials investigating this strategy have been
      underwhelming to date. While efficacy may be hampered by a narrow therapeutic
      index, the contribution of biologic heterogeneity in the response of KRAS-mutant
      NSCLCs to MEKi/PI3Ki has been largely unexplored. In this study, we find that
      most human KRAS-mutant NSCLC cell lines fail to undergo marked apoptosis in
      response to MEKi/PI3Ki, which is key for tumor responsiveness in vivo. This
      heterogeneity of apoptotic response occurs despite relatively uniform induction
      of growth arrest. Using a targeted short hairpin RNA screen of BCL-2 family
      members, we identify BIM, PUMA, and BCL-XL as key regulators of the apoptotic
      response induced by MEKi/PI3Ki, with decreased expression of BIM and PUMA
      relative to BCL-XL in cell lines with intrinsic resistance. In addition, by
      modeling adaptive resistance to MEKi/PI3Ki both in vitro and in vivo, we find
      that, upon the development of resistance, tumors have a diminished apoptotic
      response due to downregulation of BIM and PUMA. These results suggest that the
      inability to induce apoptosis may limit the effectiveness of MEKi/PI3Ki for KRAS
      mutant NSCLCs by contributing to intrinsic and adaptive resistance to this
      therapy.

PMID- 24675363
TI  - Tuberculosis antigen-induced expression of IFN-alpha in tuberculosis patients
      inhibits production of IL-1beta.
AB  - The mechanism by which IFN-alpha regulates the host response to Mycobacterium
      tuberculosis (M.tb) infection in humans is poorly understood. In the present
      study, we found that freshly isolated pleural fluid mononuclear cells (PFMCs)
      from tuberculous pleural effusion but not peripheral blood mononuclear cells
      (PBMCs) spontaneously expressed IFN-alpha and IL-1beta in vivo. In addition,
      exogenous IFN-alpha significantly inhibited production of IL-1beta in PFMCs after
      stimulation with Bacillus Calmette-Guerin (BCG). To further evaluate the effect
      of endogenous IFN-alpha on BCG-induced IL-1beta production, a neutralizing
      antibody to IFN-alpha was added to the cultures of BCG-stimulated PFMCs. As
      expected, neutralization of IFN-alpha by antibody significantly enhanced the
      production of IL-1beta. Notably, we showed that IFN-alpha inhibited production of
      IL-1beta through 2 distinct mechanisms: IFN-alpha signaling, via the STAT1
      transcription factor, suppressed caspase-1-dependent IL-1beta maturation, and IFN
      alpha induced the production of IL-10 in a STAT1-dependent manner in which IL-10
      reduced the abundance of IL-1beta. In contrast, we found that IFN-alpha enhanced
      the production of IFN-gamma, and IFN-gamma also suppressed IL-1beta production in
      the PFMCs during BCG stimulation. Our findings demonstrate that IFN-alpha employs
      distinct pathways for regulating IL-1beta production and reveal that in the case
      of M.tb infection, the induction of IFN-alpha and IFN-gamma might be associated
      with M.tb immune escape and disease progression in infected humans.-Ma, J., Yang,
      B., Yu, S., Zhang, Y., Zhang, X., Lao, S., Chen, X., Li, B., Wu, C. Tuberculosis
      antigen-induced expression of IFN-alpha in tuberculosis patients inhibits
      production of IL-1beta. 

PMID- 24675364
TI  - Two sides of the same coin: stem cells in cancer and regenerative medicine.
AB  - Multipotent stromal cells (MSCs) derived from bone marrow, adipose tissue, cord
      blood, and other origins have recently received much attention as potential
      therapeutic agents with beneficial immunomodulatory and regenerative properties.
      In their native tissue environment, however, such cells also appear to have
      essential functions in building and supporting tumor microenvironments, providing
      metastatic niches, and maintaining cancer hallmarks. Here, we consider the varied
      roles of these tissue-resident stroma-associated cells, synthesize recent and
      emerging discoveries, and discuss the role, potential, and clinical applications
      of MSCs in cancer and regenerative medicine.-Ilmer, M., Vykoukal, J., Recio
      Boiles, A., Coleman, M., Alt, E. Two sides of the same coin: stem cells in cancer
      and regenerative medicine. 

PMID- 24675365
TI  - Chromatin compaction by condensin I, intra-kinetochore stretch and tension, and
      anaphase onset, in collective spindle assembly checkpoint interaction.
AB  - The control mechanism in mitosis and meiosis by which cells decide to inhibit or
      allow segregation, the so-called spindle assembly checkpoint (SAC), increases the
      fidelity of chromosome segregation. It acts like a clockwork mechanism which
      measures time in units of stable attachments of microtubules (MTs) to
      kinetochores (the order parameter). Stable MT-kinetochore attachments mediate
      poleward forces and 'unstable' attachments, acting alone or together with motor
      proteins on kinetochores via chromosomes, antipoleward forces. Stable and
      unstable attachments could be separated, and the non-equilibrium integrated MT
      mediated force acting on stably attached kinetochores was derived in a collective
      interaction (Matsson 2009 J. Phys.: Condens. Matter 21 502101), in which
      kinetochores were treated as rigid protein complexes. As forces and tension in
      that model became equally distributed in all bioriented sister chromatid (SC)
      pairs, segregation was inhibited without need of a 'wait-anaphase' signal. In
      this generalization, the kinetochore is divided into an inner chromatin proximal
      complex and an outer MT proximal complex, and the integrated MT mediated force is
      divided into an integrated poleward and an integrated antipoleward force. The
      model also describes the collective interaction of condensin I with chromatin,
      which together with the MT mediated dynamics yields the putative in vivo tension
      in kinetochores and centromeric and pericentromeric chromatin, as a non-linear
      function of the order parameter. Supported by the compaction force and an
      increased stiffness in chromatin towards the end of metaphase, the two opposing
      integrated MT mediated poleward forces, together with metaphase oscillations,
      induce a swift and synchronized anaphase onset by first increasing the intra
      kinetochore stretch. This increase lowers the SAC energy threshold, making a
      cleavage by separase of all cohesin tethering SC pairs in anaphase energetically
      possible, thereby reducing the risk for aneuploidy and cancer. It is also shown
      how this risk might increase in condensin I depleted cells. Moreover, a solution
      is provided to the fundamental statistical physics problem with a system
      containing an increasing number of particles (molecular complexes) that become
      strongly correlated in space. 

PMID- 24675366
TI  - Characterization of estrogen receptor alpha activities in polychlorinated
      biphenyls by in vitro dual-luciferase reporter gene assay.
AB  - Polychlorinated biphenyls (PCBs) are thought to cause adverse health effects,
      particularly endocrine disruption. However, results on the estrogenic activities
      of a large set of PCB congeners through hormone receptors have not been fully
      studied. In this study, we evaluated the anti/estrogenic effects of 20 PCBs using
      an in vitro dual-luciferase reporter gene assay. PCB 18, 28, 49, 52, 99, 101,
      103, 110, and 128 exhibited estrogenic effects, whereas PCB 118, 138, 163, 170,
      180, 187, 194, 199 and 203 behaved as anti-estrogens. In particular, PCB 30 and
      44 exhibited both agonistic and antagonistic activities in the dual-luciferase
      reporter gene assay. The results obtained from the dual-luciferase reporter gene
      assay, yeast two-hybrid assay and E-SCREEN were compared, suggesting that the
      dual-luciferase reporter gene assay is a useful approach for high-throughput
      screening. We also predicted the possible relationship between the chemical
      structures and the estrogenic effects of PCBs. 

PMID- 24675367
TI  - Repeated phytoextraction of four metal-contaminated soils using the cadmium/zinc
      hyperaccumulator Sedum plumbizincicola.
AB  - A cadmium/zinc hyperaccumulator extracted metals from four contaminated soils
      over three years in a glasshouse experiment. Changes in plant metal uptake and
      soil total (aqua regia-extractable) and available metals were investigated. Plant
      Cd concentrations in a high-Cd acid soil and plant Zn concentrations in two acid
      soils decreased during repeated phytoextraction and were predicted by soil
      available metal concentrations. However, on repeated phytoextraction, plant Cd
      concentrations remained constant in lightly Cd-polluted acid soils, as did plant
      Cd and Zn in alkaline soils, although soil available metal concentrations
      decreased markedly. After phytoextraction acid soils showed much higher total
      metal removal efficiencies, indicating possible suitability of phytoextraction
      for acid soils. However, DGT-testing, which takes soil metal re-supply into
      consideration, showed substantial removal of available metal and distinct
      decreases in metal supply capacity in alkaline soils after phytoextraction,
      suggesting that a strategy based on lowering the bioavailable contaminant might
      be feasible. 

PMID- 24675368
TI  - Development of a novel method for quantification of autophagic protein
      degradation by AHA labeling.
AB  - Autophagy is a catabolic process during which cellular components including
      protein aggregates and organelles are degraded via a lysosome-dependent process
      to sustain metabolic homeostasis during nutrient or energy deprivation. Measuring
      the rate of proteolysis of long-lived proteins is a classical assay for
      measurement of autophagic flux. However, traditional methods, such as a
      radioisotope labeling assay, are technically tedious and have low sensitivity.
      Here, we report a novel method for quantification of long-lived protein
      degradation based on L-azidohomoalanine (AHA) labeling in mouse embryonic
      fibroblasts (MEFs) and in human cancer cells. AHA is a surrogate for L
      methionine, containing a bio-orthogonalazide moiety. When added to cultured
      cells, AHA is incorporated into proteins during active protein synthesis. After a
      click reaction between an azide and an alkyne, the azide-containing proteins can
      be detected with an alkyne-tagged fluorescent dye, coupled with flow cytometry.
      Induction of autophagy by starvation or mechanistic target of rapamycin (MTOR)
      inhibitors was able to induce a significant reduction of the fluorescence
      intensity, consistent with other autophagic markers. Coincidently, inhibition of
      autophagy by pharmacological agents or by Atg gene deletion abolished the
      reduction of the fluorescence intensity. Compared with the classical radioisotope
      pulse-labeling method, we think that our method is sensitive, quantitative,
      nonradioactive, and easy to perform, and can be applied to both human and animal
      cell culture systems.

PMID- 24675369
TI  - Optimization of systemic treatments for chronic plaque psoriasis. Recommendations
      for switching and transitioning.
AB  - AIM: The aim of this study was to provide practical recommendations for
      optimizing the use of conventional and biological systemic treatments for
      moderate-severe chronic plaque psoriasis, particularly in case of transitioning
      and switching. METHODS: A total number of 147 dermatologists from 33 different
      countries including Italy achieved consensus in providing practical
      recommendations for the use of conventional and biological treatments for
      moderate to severe psoriasis based on systematic literature review and/or expert
      opinion. RESULTS: In general, the continuous treatment regimen should be
      preferred in order to achieve a complete and long-term control of psoriasis.
      However, the treatment could be stopped or the dose reduced in case of complete
      disease clearance. A conventional drug could be associated to biological
      treatment in selected cases. Transitioning and/or switching could be considered
      in case of inefficacy or intolerance. A period of wash up is required if
      transitioning or switching is due to safety issues. CONCLUSION: This study
      provides practical suggestions for the optimal use of conventional and biological
      treatments for chronic plaque psoriasis.

PMID- 24675370
TI  - Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain
      in dogs: a randomized, double-blinded, placebo-controlled clinical trial.
AB  - The aim of this study was to investigate the efficacy of intra-articular (IA)
      botulinum toxin A (IA BoNT A) for the treatment of osteoarthritic joint pain in
      dogs. The study was a placebo-controlled, randomized, double-blinded clinical
      trial with parallel group design and 12-week follow-up. Thirty-six dogs with
      chronic lameness due to stifle, hip or elbow osteoarthritis were randomized to
      receive an IA injection of 30IU of BoNT A or placebo. The main outcome variables
      were vertical impulse (VI) and peak vertical force (PVF) measured with a force
      platform, and Helsinki chronic pain index (HCPI). Subjective pain score and the
      need for rescue analgesics were secondary variables. The response to treatment
      was assessed as the change from baseline to each examination week. The variables
      were analyzed by ANOVA with repeated measurements and results were considered
      statistically significant if P ? 0.05. The improvement from baseline to 12 weeks
      after baseline was statistically significant in VI, PVF and HCPI in the treatment
      group (P=0.001, P=0.054 and P=0.053, respectively). Additionally, there were
      statistically significant improvements in VI in the treatment group at 2, 4 and 8
      weeks after baseline (P=0.037, P=0.016 and P=0.016, respectively). The difference
      between groups in improvement in VI was statistically significant at 12weeks
      after baseline (P=0.005). There was no significant change in the subjective pain
      score or in the requirement for rescue analgesics in either group. No major
      adverse events thought to be related to trial protocol were detected. These
      results suggest that IA BoNT A has some efficacy in reducing osteoarthritic pain
      in dogs.

PMID- 24675371
TI  - Critical parameters involved in producing microspheres by prilling of molten
      lipids: from theoretical prediction of particle size to practice.
AB  - The aim of this work was to identify the key parameters which influence the
      running of the prilling process with lipid material from the initial melting to
      the formation of solid microspheres. The microsphere size would essentially
      result from break-up at the Rayleigh-Weber's wavelength which mostly depends on
      the liquid properties (mass density, surface tension and dynamic viscosity).
      After molten liquid extrusion through the nozzle, the cooling rate is very fast
      and the instantaneous temperature of the liquid jet decreases rapidly of 0.2-0.3 
      degrees C during the duration of the droplet formation (1-2 ms). This leads to no
      significant modification of the physical characteristics of the lipids and only a
      very slight change in the dynamic viscosity. Consequently, no significant effect
      on the optimal wavelength lambda(W) and on droplet formation can occur. However,
      coalescence of liquid droplets has been observed during their fall, probably
      caused by turbulence into the air column, leading to a minor population of larger
      microspheres.

PMID- 24675373
TI  - Ediacaran matground ecology persisted into the earliest Cambrian.
AB  - The beginning of the Cambrian was a time of marked biological and sedimentary
      changes, including the replacement of Proterozoic-style microbial matgrounds by
      Phanerozoic-style bioturbated mixgrounds. Here we show that Ediacaran-style
      matground-based ecology persisted into the earliest Cambrian. Our study in the
      type section of the basal Cambrian in Fortune Head, Newfoundland, Canada reveals
      widespread microbially induced sedimentary structures and typical Ediacaran-type
      matground ichnofossils. Ediacara-type body fossils are present immediately below
      the top of the Ediacaran but are strikingly absent from the overlying Cambrian
      succession, despite optimal conditions for their preservation, and instead the
      microbial surfaces are marked by the appearance of the first abundant arthropod
      scratch marks in Earth evolution. These features imply that the disappearance of
      the Ediacara biota represents an abrupt evolutionary event that corresponded with
      the appearance of novel bilaterian clades, rather than a fading away owing to the
      gradual elimination of conditions appropriate for Ediacaran preservation. 

PMID- 24675372
TI  - Internet-based cognitive behavioral therapy for patients with chronic somatic
      conditions: a meta-analytic review.
AB  - BACKGROUND: Patients with chronic somatic conditions face unique challenges
      accessing mental health care outside of their homes due to symptoms and physical
      limitations. Internet-based cognitive behavioral therapy (ICBT) has shown to be
      effective for various psychological conditions. The increasing number of recent
      trials need to be systematically evaluated and quantitatively analyzed to
      determine whether ICBT is also effective for chronic somatic conditions and to
      gain insight into the types of problems that could be targeted. OBJECTIVE: Our
      goal was to describe and evaluate the effectiveness of guided ICBT interventions
      for chronic somatic conditions on general psychological outcomes, disease-related
      physical outcomes, and disease-related impact on daily life outcomes. The role of
      treatment length was also examined. METHODS: PubMed, PsycINFO, and Embase were
      searched from inception until February 2012, by combining search terms indicative
      of effect studies, Internet, and cognitive behavioral therapy. Studies were
      included if they fulfilled the following six criteria: (1) randomized controlled
      trial, (2) Internet-based interventions, (3) based on cognitive behavioral
      therapy, (4) therapist-guided, (5) adult (>=18 years old) patients with an
      existing chronic somatic condition, and (6) published in English. 23 randomized
      controlled trials of guided ICBT were selected by 2 independent raters after
      reviewing 4848 abstracts. Demographic, clinical, and methodological variables
      were extracted. Standardized mean differences were calculated between
      intervention and control conditions for each outcome and pooled using random
      effects models when appropriate. RESULTS: Guided ICBT was shown to improve all
      outcome categories with small effect sizes for generic psychological outcomes
      (effect size range 0.17-0.21) and occasionally larger effects for disease
      specific physical outcomes (effect size range 0.07 to 1.19) and disease-related
      impact outcomes (effect size range 0.17-1.11). Interventions with a longer
      treatment duration (>6 weeks) led to more consistent effects on depression.
      CONCLUSIONS: Guided ICBT appears to be a promising and effective treatment for
      chronic somatic conditions to improve psychological and physical functioning and
      disease-related impact. The most consistent improvements were found for disease
      specific outcomes, which supports the possible relevance of tailoring
      interventions to specific patient groups. Explorative analyses revealed that
      longer treatment length holds the promise of larger treatment effects for the
      specific outcome of depression. While the current meta-analysis focused on
      several chronic somatic conditions, future meta-analyses for separate chronic
      somatic conditions can further consolidate these results, also in terms of cost
      effectiveness.

PMID- 24675374
TI  - Anterior corneal buttons from DSAEK donor tissue can be stored in optisol GS for
      later use in tectonic lamellar patch grafting.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of storing
      anterior corneal buttons split from donor Descemet stripping automated
      endothelial keratoplasty (DSAEK) tissue for later use in tectonic lamellar patch
      grafting. METHODS: Donor corneas for DSAEK were split into anterior and posterior
      lamellae using a 350-MUm depth microkeratome, and the remaining anterior corneal
      buttons were stored for up to 4 weeks at 4 degrees C in Optisol GS before use in
      patch grafting of the cornea and sclera. RESULTS: Optisol GS-preserved anterior
      lamellar patch grafts successfully restored and maintained corneoscleral
      integrity after the removal of limbal dermoids (5 cases), after the coverage of
      the exposed polypropylene suture ends of scleral fixated posterior chamber
      intraocular lenses (2 cases), corneoscleral melting after pterygium excision (3
      cases), sterile corneal ulceration with or without perforation (5 cases), Mooren
      ulceration (3 cases), and pseudomonas corneal ulceration with impending
      perforation (1 case). It was also used as a temporary substitute while waiting
      for a full-thickness corneal graft in a fulminant candida infection after DSAEK
      (1 case). All grafts remained structurally intact at the last postoperative
      examination of 19.2 +/- 7.6 months after the tectonic surgery. CONCLUSIONS:
      Anterior corneal buttons from DSAEK donor tissue may be stored in Optisol GS for
      later use in tectonic patch grafting. This method obviates the longer operating
      time required for the surgeon to manually dissect the donor cornea in the
      operating room and reduces the wastage of precious donor corneas in countries
      where there are chronic shortages of eye bank donor tissue.

PMID- 24675375
TI  - Prone positioning to facilitate graft adherence in the late postoperative period
      after descemet stripping automated endothelial keratoplasty.
AB  - PURPOSE: The aim of this study was to report the use of prone positioning to
      facilitate graft adherence in the late postoperative period after Descemet
      stripping automated endothelial keratoplasty (DSAEK). METHODS: A 75-year-old
      woman with Fuchs dystrophy had repeated endothelial graft detachments after
      simultaneous DSAEK and phacoemulsification cataract surgery. Multiple attempts in
      the operating room to reposition the tissue, including placement of air into the
      anterior chamber, postoperative face-up positioning, and the use of new donor
      tissue, were unsuccessful. In the late postoperative period, the patient was
      placed in a prone (face-down) position at home to promote graft adherence.
      RESULTS: After the maneuver, the endothelial graft was well attached, although it
      was slightly decentered. The remainder of the patient's postoperative course was
      routine, and her best-corrected visual acuity is 20/25 with a clear cornea 9
      months later. CONCLUSIONS: Prone positioning can be used as a conservative
      maneuver to promote graft adherence after DSAEK when there is difficulty in
      achieving attachment postoperatively, especially when a return trip to the
      operating room may not be practical.

PMID- 24675376
TI  - Influence of donor characteristics on descemet membrane endothelial keratoplasty.
AB  - PURPOSE: Penetrating keratoplasty is being replaced by posterior lamellar
      techniques like Descemet stripping automated endothelial keratoplasty or Descemet
      membrane endothelial keratoplasty (DMEK) for the surgical treatment of patients
      with endothelial insufficiency. Although DMEK leads to the best visual results,
      Descemet stripping automated endothelial keratoplasty is still the standard
      procedure for many surgeons because it is technically more standardized. Here, we
      investigated how donor characteristics may influence DMEK surgery. METHODS: After
      in vitro preparation of DMEK grafts (n = 28), we measured the width of the graft
      roll, which we correlated to various donor characteristics. In 31 DMEK cases, we
      measured the intraoperative time from implantation to attachment of the graft,
      which we correlated to the respective donor characteristics and endothelial cell
      loss. We used Pearson's method and a multifactorial linear model for the
      statistical assessments. RESULTS: We found a statistically significant
      correlation between donor age (P < 0.001) and endothelial cell density (P <
      0.05), and the width of the DMEK rolls. That is, older donors and grafts with
      higher endothelial cell densities formed broader graft rolls. Donor age also
      showed a trend to directly influence the unfolding time that took longer using
      younger grafts. Furthermore, the relative endothelial cell loss increased with
      longer unfolding times. CONCLUSIONS: We found that donor age and endothelial cell
      density influence the properties of DMEK grafts, and thereby the duration of the
      surgical procedure. Increased unfolding times result in higher endothelial cell
      loss. Therefore, it seems reasonable to accept preferably older donors with high
      endothelial cell densities for DMEK, which may be particularly true for
      inexperienced surgeons or complex clinical situations.

PMID- 24675377
TI  - PEG-PLGA copolymers: their structure and structure-influenced drug delivery
      applications.
AB  - In the paper, we begin by describing polyethylene glycol-poly lactic acid-co
      glycolic acid (PEG-PLGA) which was chosen as a typical model copolymer for the
      construction of nano-sized drug delivery systems and also the types of PEG-PLGA
      copolymers that were eluted. Following this we examine the structure-influenced
      drug delivery applications including nanoparticles, micelles and hydrogels. After
      that, the preparation methods for nano-sized delivery systems are presented. In
      addition, the drug loading mode of PEG-PLGA micelles is divided into three
      aspects. Finally, the drug release profiles of PEG-PLGA micelles, both in terms
      of their in vitro and in vivo characteristics, are represented. PEG-PLGA
      copolymers are very suitable for the construction of micelles as carriers for
      insoluble drugs. This article reviews the structure and the different structure
      influenced applications of PEG-PLGA copolymers, concentrating on the application
      of PEG-PLGA micelles. 

PMID- 24675378
TI  - Design, synthesis and biological evaluation of novel aminomethyl-piperidones
      based DPP-IV inhibitors.
AB  - A series of novel aminomethyl-piperidones were designed and evaluated as
      potential DPP-IV inhibitors. Optimized analogue 12v ((4S,5S)-5-(aminomethyl)-1-(2
      (benzo[d][1,3]dioxol-5-yl)ethyl)-4-(2,5-difluorophenyl)piperidin-2-one) showed
      excellent in vitro potency and selectivity for DPP-IV over other serine
      proteases. The lead compound 12v showed potent and long acting antihyperglycemic
      effects (in vivo), along with improved pharmacokinetic profile. 

PMID- 24675379
TI  - Aptamers directly radiolabeled with technetium-99m as a potential agent capable
      of identifying carcinoembryonic antigen (CEA) in tumor cells T84.
AB  - Aptamers are small oligonucleotides that are selected to bind with high affinity
      and specificity to a target molecule. Aptamers are emerging as a new class of
      molecules for radiopharmaceutical development. In this study a new method to
      radiolabel aptamers with technetium-99m ((99m)Tc) was developed. Two aptamers
      (Apt3 and Apt3-amine) selected against the carcinoembryonic antigen (CEA) were
      used. Labeling was done by the direct method and the developed complex was
      subjected to quality control tests. Radiochemical purity and stability were
      monitored by Thin Layer Chromatography. Binding and specificity assays were
      carried out in the T84 cell line (CEA+) to evaluate tumor affinity and
      specificity after radiolabeling. Aptamers were successfully labeled with (99m)Tc
      in high radiochemical yields, showing in vitro stability in presence of plasma
      and cystein. In binding assays the radiolabeled aptamer Apt3-amine showed the
      highest affinity to T84 cells. When evaluated with HeLa cells (CEA-), lower
      uptake was observed, suggesting high specificity for this aptamer. These results
      suggest that the Apt3-amine aptamer directly labeled with (99m)Tc could be
      considered a promising agent capable of identifying the carcinoembryonic antigen
      (CEA) present in tumor cells. 

PMID- 24675380
TI  - Identification of novel SIRT2-selective inhibitors using a click chemistry
      approach.
AB  - A series of 114 SIRT inhibitor candidates was assembled using 'click chemistry',
      by reacting two alkynes bearing 2-anilinobenzamide pharmacophore with 57 azide
      building blocks in the presence of Cu(I) catalyst. Screening identified two SIRT2
      selective inhibitors, which were more SIRT2-selective than AGK2, a known SIRT2
      inhibitor. These findings will be useful for further development of SIRT2
      selective inhibitors. 

PMID- 24675381
TI  - Highly potent and selective 3-N-methylquinazoline-4(3H)-one based inhibitors of B
      Raf(V600E) kinase.
AB  - Herein we describe the design of a novel series of ATP competitive B-Raf
      inhibitors via structure-based methods. These 3-N-methylquinazoline-4(3H)-one
      based inhibitors exhibit both excellent cellular potency and striking B-Raf
      selectivity. Optimization led to the identification of compound 16, a potent,
      selective and orally available agent with excellent pharmacokinetic properties
      and robust tumor growth inhibition in xenograft studies. Our work also
      demonstrates that by replacing an aryl amide with an aryl sulfonamide, a
      multikinase inhibitor such as AZ-628, can be converted to a selective B-Raf
      inhibitor, a finding that should have broad application in kinase drug discovery.

PMID- 24675382
TI  - Does cancer risk increase with HbA1c, independent of diabetes?
AB  - BACKGROUND: The risks for several cancer types are increased in people with
      diabetes. Hyperglycaemia, hyperinsulinaemia, inflammation and altered hormonal
      concentrations are common characteristics between the two diseases and can all be
      linked to hyperglycaemia. METHODS: Here, we use glycated haemoglobin (HbA1c) as a
      biomarker for chronic hyperglycaemia. We explore whether cancer risk increases
      with HbA1c, independent of diabetes, and, therefore, if risk is already increased
      below the diabetic HbA1c range, by analysing data from current studies linking
      HbA1c to risk of several cancer types. RESULTS: The data reveal that chronic
      hyperglycaemia correlates with increased cancer risk for a number of cancers,
      except prostate cancer. Evidence is also provided that risk is already increased
      in the pre-diabetic and normal ranges for several cancers. CONCLUSIONS: These
      results merit urgent investigation into the risks and advantages of updating
      recommendations for stricter glycaemic control in diabetic and non-diabetic
      subjects, as this could help reduce the risk of cancer incidence and mortality.

PMID- 24675383
TI  - The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in
      breast cancer patients.
AB  - BACKGROUND: The elevation of the platelet-to-lymphocyte ratio (PLR), an easily
      applicable blood test based on platelet and lymphocyte counts has been associated
      with poor prognosis in patients with different types of cancer. The present study
      was aimed to investigate the prognostic significance of the preoperative PLR in a
      large cohort of breast cancer patients. METHODS: Data from 793 consecutive non
      metastatic breast cancer patients, treated between 1999 and 2004, were evaluated
      retrospectively. The optimal cutoff values for the PLR were calculated using
      receiver operating curve analysis. Cancer-specific survival (CSS), overall
      survival (OS) as well as distant metastasis-free survival (DMFS) were assessed
      using the Kaplan-Meier method. To evaluate the independent prognostic
      significance of PLR, multivariable Cox regression models were applied for all
      three different end points. RESULTS: Univariable analysis revealed a significant
      association between the elevated preoperative PLR and CSS (hazard ratio (HR):
      2.75, 95% confidence interval (CI): 1.57-4.83, P<0.001) that remained
      statistically significant in multivariable analysis (HR: 2.03, 95% CI: 1.03-4.02,
      P=0.042). An increased PLR was also significantly associated with decreased OS in
      univariable (HR: 2.45, 95% CI: 1.43-4.20, P=0.001) and in multivariable analysis
      (HR: 1.92, 95% CI: 1.01-3.67, P=0.047). Furthermore, univariable analysis showed
      a significant impact of increased PLR on DMFS (HR: 2.02, 95% CI: 1.18-3.44,
      P=0.010). Subgroup analysis revealed significant associations of the elevated PLR
      on the primary end point CSS for all breast cancer subtypes. This association
      retained its significance in multivariable analysis in patients with luminal B
      tumours (HR: 2.538, 95% CI: 1.043-6.177, P=0.040). CONCLUSIONS: In this study, we
      identified the preoperative PLR as an independent prognostic marker for survival
      in breast cancer patients. Independent validation of our findings is needed.

PMID- 24675384
TI  - The intratumoural subsite and relation of CD8(+) and FOXP3(+) T lymphocytes in
      colorectal cancer provide important prognostic clues.
AB  - BACKGROUND: To find improved tools for prognostic evaluation in patients with
      colorectal cancer (CRC), we have analysed how infiltration of cytotoxic T
      lymphocytes (CD8(+)) and regulatory T lymphocytes (FoxP3(+)) correlates to
      prognosis, not only according to quantity and relation, but also to subsite
      within tumours of different molecular characteristics (microsatellite instability
      and CpG island methylator phenotype status). METHODS: CD8 and FOXP3 expression
      was evaluated by immunohistochemistry in 426 archival tumour tissue samples from
      patients surgically resected for CRC. The average infiltration of CD8(+) and
      FOXP3(+) cells was assessed along the tumour invasive front, in the tumour centre
      and within the tumour epithelium (intraepithelial). RESULTS: We found that
      infiltration of CD8(+) T lymphocytes within the tumour epithelium provided the
      strongest prognostic information (P<0.001). At the tumour invasive front and
      tumour centre, FOXP3 expression withheld the strongest association to prognosis
      (P<0.001), suggesting FOXP3(+) T-lymphocyte infiltration to be a better
      prognostic tool than CD8(+) T lymphocytes at these intratumoural subsites. We
      further analysed the possible prognostic impact of the relation between these T
      cell subsets, finding that a high intraepithelial CD8 expression was associated
      with a better patient outcome, independent of FOXP3 infiltration. In groups of
      low intraepithelial CD8 expression, however, a high infiltration rate of FOXP3(+)
      cells at the tumour invasive front, significantly improved prognosis.
      CONCLUSIONS: Analyses of intraepithelial infiltration of CD8(+) T lymphocytes,
      infiltration of FOXP3(+) T lymphocytes at the tumour front or centre, and the
      relation between these subsets, may be a valuable tool for predicting prognosis
      in colon cancer.

PMID- 24675386
TI  - An informational pathway to the development of a contamination-related memory
      bias.
AB  - BACKGROUND AND OBJECTIVES: Following from previous research in which post
      encoding suggestions of threat led to the development of a memory bias (in the
      presumed absence of an attentional bias; Senn & Radomsky, 2012), we sought to
      examine whether the development of a similar threat-relevant memory bias could be
      fostered via a purely informational pathway. METHODS: A vignette about a
      classroom interaction was read aloud to (n = 96) undergraduate participants who
      then completed a post-encoding recall test. Participants were told that the
      experimenter forgot to read the last sentence of the vignette, and were then
      randomly assigned either to the Threat condition, in which the additional
      statement indicated that a character in the vignette had a highly contagious flu,
      or to the No-Threat condition, in which the additional statement indicated that a
      character in the vignette had been accepted to graduate school. A second recall
      test was then administered. RESULTS: Participants in the Threat condition (but
      not those in the No-Threat condition) demonstrated aproportionate memory bias in
      favor of threatening information. This bias was not evident at the initial recall
      test. LIMITATIONS: Time spent engaging in active recall was not assessed. Also,
      although the study was designed to minimize demand characteristics, it is
      possible that these played a role. CONCLUSIONS: An explicit memory bias for
      threat can be created through informational means alone, even when no threat was
      present at encoding. Results are discussed in terms of pathways to fear and of
      cognitive approaches to understanding and treating anxiety disorders.

PMID- 24675385
TI  - Organic food consumption and the incidence of cancer in a large prospective study
      of women in the United Kingdom.
AB  - BACKGROUND: Organically produced foods are less likely than conventionally
      produced foods to contain pesticide residues. METHODS: We examined the hypothesis
      that eating organic food may reduce the risk of soft tissue sarcoma, breast
      cancer, non-Hodgkin lymphoma and other common cancers in a large prospective
      study of 623 080 middle-aged UK women. Women reported their consumption of
      organic food and were followed for cancer incidence over the next 9.3 years. Cox
      regression models were used to estimate adjusted relative risks for cancer
      incidence by the reported frequency of consumption of organic foods. RESULTS: At
      baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always
      eating organic food, respectively. Consumption of organic food was not associated
      with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for
      usually/always vs never=1.03, 95% confidence interval (CI): 0.99-1.07), soft
      tissue sarcoma (RR=1.37, 95% CI: 0.82-2.27), or breast cancer (RR=1.09, 95% CI:
      1.02-1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65
      0.96). CONCLUSIONS: In this large prospective study there was little or no
      decrease in the incidence of cancer associated with consumption of organic food,
      except possibly for non-Hodgkin lymphoma.

PMID- 24675387
TI  - Vaccination with a mutated variant of human Vascular Endothelial Growth Factor
      (VEGF) blocks VEGF-induced retinal neovascularization in a rabbit experimental
      model.
AB  - Vascular Endothelial Growth Factor (VEGF) is a key driver of the
      neovascularization and vascular permeability that leads to the loss of visual
      acuity of eye diseases like wet age-related macular degeneration, diabetic
      macular edema, and retinopathy of premature. Among the several anti-VEGF
      therapies under investigation for the treatment of neovascular eye diseases, our
      group has developed the vaccine candidate CIGB-247-V that uses a mutated form of
      human VEGF as antigen. In this work we evaluated if the vaccine could prevent or
      attenuate VEGF-induced retinal neovascularization in the course of a rabbit eye
      neovascularization model, based on direct intravitreal injection of human VEGF.
      Our experimental findings have shown that anti-VEGF IgG antibodies induced by the
      vaccine were available in the retina blood circulation, and could neutralize in
      situ the neovascularization effect of VEGF. CIGB-247-V vaccination proved to
      effectively reduce retinal neovascularization caused by intravitreal VEGF
      injection. Altogether, these results open the way for human studies of the
      vaccine in neovascular eye syndromes, and inform on the potential mechanisms
      involved in its effect. 

PMID- 24675388
TI  - Alcohol-impaired motor vehicle crash risk and the location of alcohol purchase.
AB  - Motor vehicle crashes involving alcohol impairment are among the leading causes
      of mortality and morbidity in the U.S. In this study, we examine how the
      probability of driving after a binge-drinking episode varies with the location of
      consumption and type of alcohol consumed. We also investigate the relationship
      between the location of alcohol purchase and the number of alcohol-impaired fatal
      motor vehicle crashes. Using multiple datasets that are representative of the
      U.S. between 2003 and 2009, we find that binge-drinkers are significantly more
      likely to drive after consuming alcohol at establishments that sell alcohol for
      on-premises consumption, e.g., from bars or restaurants, particularly after
      drinking beer. Further, per capita sales of alcohol for off-premises consumption
      are unrelated to the rate of alcohol-impaired fatal motor vehicle crashes. When
      disaggregating alcohol types, per capita sales of beer for off-premises
      consumption are negatively associated with the rate of alcohol-impaired fatal
      motor vehicle crashes. In contrast, total per capita sales of alcohol from all
      establishments (on- and off-premises) are positively related to the rate of
      alcohol-impaired fatal motor vehicle crashes and the magnitude of this
      relationship is strongest for beer sales. Thus, policies that shift consumption
      away from bars and restaurants could lead to a decline in the number of motor
      vehicle crashes. 

PMID- 24675389
TI  - The 'taking place' of health and wellbeing: towards non-representational theory.
AB  - For the last two decades health geography has focused on the dynamics between
      health and place. Although the social constructivist perspective of much research
      has provided many insights into the meanings of health and health care arguably,
      mirroring progress in the parent discipline of human geography, there could be a
      far more serious engagement with non-representational theory and the 'taking
      place' of health and health care. To showcase the importance and potential of
      this broadly, the idea of wellbeing is re-approached. The paper reflects on the
      ways wellbeing has been treated in research primarily as a meaningful and
      relatively prescribed state of life, to the neglect of process. Based on this
      critique, a qualitative study then illustrates the most immediate and everyday
      ways wellbeing might arise through 'affect'; the pre-personal mobile energies and
      intensities that result from physical encounters within assemblages of bodies and
      objects. Indeed, theoretically the findings support the proposition that, at one
      level, wellbeing might not be taken from environment but instead might emerge as
      the affective environment. They certainly raise awareness of how much in health
      might originate at the surface, prior to meaning, within life's infinite spatial
      doings, and thus they launch some final thoughts on the wider challenges and
      opportunities for non-representational health geographies. 

PMID- 24675390
TI  - Arsenic-induced sub-lethal stress reprograms human bronchial epithelial cells to
      CD61- cancer stem cells.
AB  - In the present report, we demonstrate that sub-lethal stress induced by
      consecutive exposure to 0.25 uM arsenic (As3+) for six months can trigger
      reprogramming of the human bronchial epithelial cell (BEAS-2B) to form cancer
      stem cells (CSCs) without forced introduction of the stemness transcription
      factors. These CSCs formed from As3+-induced sub-lethal stress featured with an
      increased expression of the endogenous stemness genes, including Oct4, Sox2,
      Klf4, Myc, and others that are associated with the pluripotency and self-renewal
      of the CSCs. Flow cytometry analysis indicated that 90% of the CSC cells are CD61
      , whereas 100% of the parental cells are CD61+. These CD61- CSCs are highly
      tumorigenic and metastatic to the lung in xenotransplantation tests in NOD/SCID
      Il2rgamma-/- mice. Additional tests also revealed that the CD61- CSCs showed a
      significant decrease in the expression of the genes important for DNA repair and
      oxidative phosphorylation. To determine the clinical relevance of the above
      findings, we stratified human lung cancers based on the level of CD61 protein and
      found that CD61low cancer correlates with poorer survival of the patients. Such a
      correlation was also observed in human breast cancer and ovarian cancer. Taken
      together, our findings suggest that in addition to the traditional approaches of
      enforced introduction of the exogenous stemness circuit transcription factors,
      sub-lethal stress induced by consecutive low dose As3+ is also able to convert
      non-stem cells to the CSCs. 

PMID- 24675391
TI  - Multilayered pigment epithelial detachment in neovascular age-related macular
      degeneration.
AB  - PURPOSE: To describe the spectral domain optical coherence tomography findings in
      eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving
      intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.
      METHODS: Retrospective observational case series of patients with chronic
      fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding
      spectral domain optical coherence tomography scans of chronic PEDs were studied
      in detail over multiple visits. The internal structure within the sub-PED
      compartment was analyzed, characteristic features were identified, and then
      correlated with visual outcome. RESULTS: Thirty-eight eyes of 34 patients with
      fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50
      (range, 20/20-20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF
      injections (median, 23.0; range, 3-70) administered over a mean of 36.9 months
      (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly
      organized layered hyperreflective bands was noted within each PED. Nineteen eyes
      demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the
      undersurface of the retinal pigment epithelium. Additionally, 25 eyes
      demonstrated a hyporeflective cavity separating the choroidal neovascularization
      complex from the underlying choroid. CONCLUSION: Chronic fibrovascular PEDs
      receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex
      of highly organized, layered, hyperreflective bands, termed a "multilayered PED,"
      which is often seen in conjunction with neovascular tissue adherent to the
      undersurface of the retinal pigment epithelium monolayer. On the basis of
      previous histopathologic correlations, these bands may represent a fibrous tissue
      complex with contractile properties. An associated hyporeflective space, termed a
      "pre-choroidal cleft," separates the fusiform complex from the underlying choroid
      and may be due to contraction, the exudation of fluid, or both. Many of these
      eyes maintain good visual acuity, presumably because the neovascular and
      cicatricial process is suppressed within the sub-retinal pigment epithelium space
      by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor
      population through preservation of the retinal pigment epithelium.

PMID- 24675392
TI  - alpha-Methylacyl-CoA racemase (P504S) is a useful marker for the differential
      diagnosis of solid pseudopapillary neoplasm of the pancreas.
AB  - The differential diagnosis of solid pseudopapillary neoplasm (SPN) from some
      other nonductal pancreatic tumors may be difficult because of similarities in
      morphological features. Therefore, immunohistochemical staining is frequently
      necessary. alpha-Methylacyl-CoA racemase (AMACR) is a diagnostically useful
      marker for prostatic cancer and papillary renal cell carcinoma. The aim of this
      study was to investigate AMACR as a new immunohistochemical marker to
      differentiate SPNs from other nonductal pancreatic tumors. We investigated
      immunohistochemical staining for AMACR in 26 SPNs, 21 pancreatic neuroendocrine
      tumors, and 7 acinar cell carcinomas. All cases of SPN showed granular
      cytoplasmic expression of AMACR, whereas all cases of pancreatic neuroendocrine
      tumors and acinar cell carcinomas were negative for this immunohistochemical
      marker. Hence, our findings demonstrate for the first time that AMACR is a useful
      immunohistochemical marker for the differential diagnosis of SPNs. 

PMID- 24675393
TI  - Reply to "triple or dual therapy for HCV-1 naive patients? Optimizing selection
      tools".

PMID- 24675394
TI  - The impact of educational materials on compliance and persistence rates with
      adjuvant aromatase inhibitor treatment: first-year results from the compliance of
      aromatase inhibitors assessment in daily practice through educational approach
      (CARIATIDE) study.
AB  - The CARIATIDE study was designed to assess the impact of educational materials
      (EMs) on compliance and persistence rates with aromatase inhibitor (AI) treatment
      in postmenopausal women with hormone-receptor-positive early breast cancer.
      Patients were randomized to standard AI treatment (Group A; N = 1379) or standard
      AI treatment plus EMs containing information on a range of breast-cancer-related
      topics (Group B; N = 1379). Standardized questionnaires assessed investigator
      perceived levels of care and evaluated patient compliance and behavior. At 1
      year, there was no significant difference in compliance between Group A and Group
      B (81% vs. 82%, p = 0.4524). However, higher compliance in patients receiving EMs
      was observed in Sweden/Finland (p = 0.0246). Compliance with initial AI and
      persistence rate were not significantly altered by EM. Other factors associated
      with improved compliance, irrespective of EMs, e.g. administration of
      chemotherapy were identified.

PMID- 24675396
TI  - A combined adsorption and flocculation process for producing lignocellulosic
      complexes from spent liquors of neutral sulfite semichemical pulping process.
AB  - The spent liquor (SL) of a neutral sulfite semichemical pulping process contains
      lignocelluloses that are currently treated in a waste water system. In this work,
      an adsorption process using activated carbon (AC) was considered for isolating
      the lignin and hemicelluloses from SL. The maximum adsorptions of 0.9 g/g lignin
      and 0.43 g/g of hemicelluloses on AC were achieved under the conditions of 30
      degrees C, pH 7 and 3h with SL/AC weight ratio of 90. The addition of
      polydiallyldimethylammonium chloride (PDADMAC) to the SL/AC system significantly
      improved the adsorption of lignin to 2.5 g/g on AC. The molecular weight of
      PDADMAC considerably affected the results in that the higher MW PDADMAC led to
      less lignin, but more hemicelluloses, turbidity and chemical oxygen demand
      removals from the SL. The thermal analysis also revealed that the higher MW
      PDADMAC generated precipitates with a lower incineration temperature and heating
      value.

PMID- 24675395
TI  - Technology-assisted patient access to clinical information: an evaluation
      framework for blue button.
AB  - BACKGROUND: Patient access to clinical information represents a means to improve
      the transparency and delivery of health care as well as interactions between
      patients and health care providers. We examine the movement toward augmenting
      patient access to clinical information using technology. Our analysis focuses on
      "Blue Button," a tool that many health care organizations are implementing as
      part of their Web-based patient portals. OBJECTIVE: We present a framework for
      evaluating the effects that technology-assisted access to clinical information
      may have on stakeholder experiences, processes of care, and health outcomes.
      METHODS: A case study of the United States Department of Veterans Affairs' (VA)
      efforts to make increasing amounts of clinical information available to patients
      through Blue Button. Drawing on established collaborative relationships with
      researchers, clinicians, and operational partners who are engaged in the VA's
      ongoing implementation and evaluation efforts related to Blue Button, we assessed
      existing evidence and organizational practices through key informant interviews,
      review of documents and other available materials, and an environmental scan of
      published literature and the websites of other health care organizations.
      RESULTS: Technology-assisted access to clinical information represents a
      significant advance for VA patients and marks a significant change for the VA as
      an organization. Evaluations of Blue Button should (1) consider both processes of
      care and outcomes, (2) clearly define constructs of focus, (3) examine
      influencing factors related to the patient population and clinical context, and
      (4) identify potential unintended consequences. CONCLUSIONS: The proposed
      framework can serve as a roadmap to guide subsequent research and evaluation of
      technology-assisted patient access to clinical information. To that end, we offer
      a series of related recommendations.

PMID- 24675397
TI  - Economic process to produce biohydrogen and volatile fatty acids by a mixed
      culture using vinasse from sugarcane ethanol industry as nutrient source.
AB  - This work evaluates the potential of vinasse (a waste obtained at the bottom of
      sugarcane ethanol distillation columns) as nutrient source for biohydrogen and
      volatile fatty acids production by means of anaerobic consortia. Two different
      media were proposed, using sugarcane juice or molasses as carbon source. The
      consortium LPBAH1 was selected for fermentation of vinasse supplemented with
      sugarcane juice, resulting in a higher H2 yield of 7.14 molH2 molsucrose(-1) and
      hydrogen content in biogas of approx. 31%, while consortium LPBAH2 resulted in
      3.66 molH2/molsucrose and 32.7% hydrogen content in biogas. The proposed process
      showed a rational and economical use for vinasse, a mandatory byproduct of the
      renewable Brazilian energy matrix.

PMID- 24675398
TI  - Biomass supply chain optimisation for Organosolv-based biorefineries.
AB  - This work aims at providing a Mixed Integer Linear Programming modelling
      framework to help define planning strategies for the development of sustainable
      biorefineries. The up-scaling of an Organosolv biorefinery was addressed via
      optimisation of the whole system economics. Three real world case studies were
      addressed to show the high-level flexibility and wide applicability of the tool
      to model different biomass typologies (i.e. forest fellings, cereal residues and
      energy crops) and supply strategies. Model outcomes have revealed how supply
      chain optimisation techniques could help shed light on the development of
      sustainable biorefineries. Feedstock quality, quantity, temporal and geographical
      availability are crucial to determine biorefinery location and the cost-efficient
      way to supply the feedstock to the plant. Storage costs are relevant for
      biorefineries based on cereal stubble, while wood supply chains present dominant
      pretreatment operations costs. 

PMID- 24675399
TI  - Distributions of single-molecule properties as tools for the study of dynamical
      heterogeneities in nanoconfined water.
AB  - The explicit trend of the distribution functions of single-molecule rotational
      relaxation constants and atomic mean-square displacement are used to study the
      dynamical heterogeneities in nanoconfined water. The trend of the single-molecule
      properties distributions is related to the dynamic heterogeneities, and to the
      dynamic crossovers found in water clusters of different shapes and sizes and
      confined in a variety of zeolites. This was true in all the cases that were
      considered, in spite of the various shapes and sizes of the clusters. It is
      confirmed that the high temperature dynamical crossover occurring in the
      temperature range 200-230 K can be interpreted at a molecular level as the
      formation of almost translationally rigid clusters, characterized by some
      rotational freedom, hydrogen bond exchange and translational jumps as cage-to
      cage processes. We also suggest a mechanism for the low temperature dynamical
      crossover (LTDC), falling in the temperature range 150-185 K, through which the
      adsorbed water clusters are made of nearly rigid sub-clusters, slightly
      mismatched, and thus permitting a relatively free librational motion at their
      borders. It appears that the condition required for LTDC to occur is the presence
      of highly heterogeneous environments for the adsorbed molecules, with some
      dangling hydrogen bonds or weaker than water-water hydrogen bonds. Under these
      conditions some dynamics are permitted at very low temperature, although most
      rotational motion is frozen. Therefore, it is unlikely, though not entirely
      excluded, that LTDC will be found in supercooled bulk water where no
      heterogeneous interface is present. 

PMID- 24675400
TI  - Epigenetic plasticity of Cd8a locus during CD8(+) T-cell development and effector
      differentiation and reprogramming.
AB  - Modulation of CD8 coreceptor levels can profoundly affect T-cell sensitivity to
      antigen. Here we show that the heritable downregulation of CD8 during type 2
      polarization of murine CD8(+) effector T cells in vitro and in vivo is associated
      with CpG methylation of several regions of the Cd8a locus. These epigenetic
      modifications are maintained long-term in vivo following adoptive transfer. Even
      after extended type 2 polarization, however, some CD8(low) effector cells respond
      to interferon-gamma by re-expressing CD8 and a type 1 cytokine profile in
      association with partial Cd8a demethylation. Cd8a methylation signatures in
      naive, polarized and repolarized cells are distinct from those observed during
      the initiation, maintenance and silencing of CD8 expression by developing T cells
      in the thymus. This persistent capacity for epigenetic reprogramming of
      coreceptor levels on effector CD8(+) T cells enables the heritable tuning of
      antigen sensitivity in parallel with changes in type 1/type 2 cytokine balance. 

PMID- 24675401
TI  - Signalling entropy: A novel network-theoretical framework for systems analysis
      and interpretation of functional omic data.
AB  - A key challenge in systems biology is the elucidation of the underlying
      principles, or fundamental laws, which determine the cellular phenotype.
      Understanding how these fundamental principles are altered in diseases like
      cancer is important for translating basic scientific knowledge into clinical
      advances. While significant progress is being made, with the identification of
      novel drug targets and treatments by means of systems biological methods, our
      fundamental systems level understanding of why certain treatments succeed and
      others fail is still lacking. We here advocate a novel methodological framework
      for systems analysis and interpretation of molecular omic data, which is based on
      statistical mechanical principles. Specifically, we propose the notion of
      cellular signalling entropy (or uncertainty), as a novel means of analysing and
      interpreting omic data, and more fundamentally, as a means of elucidating systems
      level principles underlying basic biology and disease. We describe the power of
      signalling entropy to discriminate cells according to differentiation potential
      and cancer status. We further argue the case for an empirical cellular entropy
      robustness correlation theorem and demonstrate its existence in cancer cell line
      drug sensitivity data. Specifically, we find that high signalling entropy
      correlates with drug resistance and further describe how entropy could be used to
      identify the achilles heels of cancer cells. In summary, signalling entropy is a
      deep and powerful concept, based on rigorous statistical mechanical principles,
      which, with improved data quality and coverage, will allow a much deeper
      understanding of the systems biological principles underlying normal and disease
      physiology. 

PMID- 24675402
TI  - Modulating and measuring Wingless signalling.
AB  - The main Wnt ligand of Drosophila activates a conserved canonical signalling
      pathway to regulate a plethora of cellular activities during development,
      regeneration and nervous system function. Here I first describe experimental
      means of measuring and modulating Wingless signalling in Drosophila cell culture.
      Various reporters have been devised by placing TCF-binding sites or DNA fragments
      from known target genes upstream of luciferase-coding sequences. Signalling can
      be activated in cells by addition of Wingless conditioned medium, treatment with
      a chemical inhibitor of Shaggy/GSK3 or transfection with a plasmid encoding
      activated Armadillo (Drosophila beta-catenin). Measuring Wingless signalling in
      intact tissue is somewhat more challenging than in cell culture. Synthetic
      transgenic reporters have been devised but further improvements are needed to
      achieve sensitive responsiveness to Wingless at all times and places. As an
      alternative, gene traps in frizzled3 and notum/wingful, two context-independent
      endogenous targets, can be used as reporters. It is hoped that further
      modification of these loci could lead to more versatile and sensitive means of
      detecting signalling. Many genetic tools are available to trigger ectopic
      signalling or prevent endogenous signalling. These mostly rely on RNAi-producing
      transgenes or the generation of mutant patches by mitotic recombination. New
      developments in genome engineering are opening further means of manipulating the
      components of Wingless signalling with exquisite temporal and spatial precision. 

PMID- 24675403
TI  - Nonsurgical oncological management of cancer pain.
AB  - PURPOSE OF REVIEW: Pain is the most common symptom in patients with advanced
      cancer and often persists despite treatment. Recent advances in oncological
      therapy and the molecular basis of cancer and pain will help to improve patient
      outcomes. RECENT FINDINGS: Chemotherapy, targeted therapy and radiotherapy are
      important components of the multidisciplinary management of cancer pain, which
      also includes early referral to specialist pain services. Cancer pain is complex
      and an understanding of the type of pain, the biology of the particular cancer as
      well as patient factors must be considered. Conventional palliative radiotherapy
      provides effective pain relief from cancer metastases, and recently
      radiopharmaceuticals have been shown to be beneficial for bone metastasis.
      Systemic cancer therapy can provide pain relief as a result of tumour shrinkage
      but recent studies suggest that benefit may also be as a consequence of
      modulation of pain signalling pathways. SUMMARY: In advanced cancers, oncological
      therapies must be considered as anti-pain treatments. Identifying molecular
      targets that have a role in both pain and cancer is an interesting strategy for
      future drug development.

PMID- 24675404
TI  - Abstracts of the 40th Annual Meeting of the European Group for Blood and Marrow
      Transplantation, 30 March - 2 April 2014, Milan, Italy.

PMID- 24675414
TI  - Plasma ATP is required for neutrophil activation in a mouse sepsis model.
AB  - Our previous work has shown that polymorphonuclear neutrophils (PMNs) require
      cellular adenosine triphosphate (ATP) release and autocrine purinergic signaling
      for their activation. Here we studied in a mouse model of cecal ligation and
      puncture (CLP) whether sepsis affects this purinergic signaling process and
      thereby alters PMN responses after sepsis. Using high-performance liquid
      chromatography, we found that plasma ATP, adenosine diphosphate (ADP), and
      adenosine monophosphate (AMP) concentrations increased up to 6-fold during the
      first 8 h after CLP, reaching top levels that were significantly higher than
      those in sham control animals without CLP. Although leukocyte and PMN counts in
      sham animals increased significantly after 4 h, these blood cell counts decreased
      in sepsis animals. CD11b expression on the cell surface of PMNs of septic animals
      was significantly higher compared with sham and untreated control animals. These
      findings suggest increased PMN activation and sequestration of PMN from the
      circulation after sepsis. Plasma ATP levels correlated with CD11b expression,
      suggesting that increased ATP concentrations in plasma contribute to PMN
      activation. We found that treatment of septic mice with the ATP receptor
      antagonist suramin diminished CD11b expression, indicating that plasma ATP
      contributes to PMN activation by stimulating P2 receptors of PMNs. Increased PMN
      activation can protect the host from invading microorganisms. However, increased
      PMN activation can also be detrimental by promoting secondary organ damage. We
      conclude that pharmacological targeting of P2 receptors may allow modulation of
      PMN responses in sepsis. 

PMID- 24675415
TI  - Differential role of T regulatory and Th17 in Swiss mice infected with Plasmodium
      berghei ANKA and Plasmodium yoelii.
AB  - The outcome of malaria infection is determined, in part, by the balance of pro
      inflammatory and regulatory immune responses. Host immune responses in disease
      including malaria are finely regulated by the opposing effects of Th17 and T
      regulatory (Treg) cells. Here we have examined the role of Treg cells and Th17
      cells during malaria infection and find that low levels of Treg cells possibly
      influence the outcome of infections with the lethal strain of Plasmodium berghei
      ANKA (PbA). In contrast, high level of Treg cells may influence the outcome of
      nonlethal Plasmodium yoelii NXL (P. yoelii) infections. We observed decreased
      expressions of key regulators of Treg inductions-TGF-beta, CD4IL-2 and IL-10
      during PbA infection, whereas their expression remains high during P. yoelii
      infection. On the other hand TNF-alpha, IL-6, IFN-gamma and IL-23 expression is
      high during PbA infection and lower during P. yoelii infection. Thus, results
      from this study suggest that the differential expression of Treg and Th17 might
      have a key role on host pathogenesis during malaria infection. The high level of
      IL-6 and low level of TGF-beta may composite of the advantaged local
      microenvironment for the production of Th17 cells in the spleen of the PBA
      infected mice and vice verse during nonlethal P. yoelii. 

PMID- 24675416
TI  - Molecular confirmation of the first autochthonous case of human babesiosis in
      Australia using a novel primer set for the beta-tubulin gene.
AB  - In 2012, the first autochthonous Australian case of human babesiosis was
      reported, after microscopic examinations of blood samples revealed intra
      erythrocytic parasites in a hospitalized 56year-old man from NSW, who died in
      2011 (Senanayake et al., 2012). Independent molecular analyses carried out in
      Australia and the USA, identified Babesia microti at the 18S ribosomal RNA (18S
      rRNA), and the beta-tubulin (beta-tubulin) gene loci. Here we present the details
      of a novel PCR-based assay for the beta-tubulin gene that was developed, during
      the original study, to corroborate the results obtained from the analysis of the
      18S rDNA. The complete phylogenetic reconstruction, based on the two loci
      sequenced from the Australian clinical isolate, is also shown here for the first
      time. 

PMID- 24675418
TI  - Novel synthesis of carbohydrate fused alpha-amino gamma-lactams and glycopeptides
      by NIS mediated ring opening of donor-acceptor substituted cyclopropanes.
AB  - alpha-Amino gamma-lactams have been synthesized from carbohydrate derived
      cyclopropanecarboxylates using N-iodosuccinimide (NIS) and NaN3. Cyclopropane
      ring opening with NIS and NaN3 in different solvents has been studied. Reductive
      cyclization of the intermediate di-azides leads to the carbohydrate fused alpha
      amino gamma-lactam and gamma-lactams. Additionally, the methodology has been
      successfully extended to the synthesis of a glycopeptide. 

PMID- 24675417
TI  - Immunization with recombinant 3-1E protein in AbISCO(r)-300 adjuvant induced
      protective immunity against Eimeria acervulina infection in chickens.
AB  - Immunostimulating complexes (ISCOMs), a kind of novel antigen presenting system,
      could enhance immune protection by antigen presentation. AbISCO(r)-300 comprising
      purified saponin, cholesterol and phosphatidyl choline is an effective ISCOM
      adjuvant. To evaluate the immune protection of recombinant 3-1E protein against
      Eimeria acervulina infection, chickens were immunized with recombinant 3-1E
      protein in combination with AbISCO(r)-300 or recombinant 3-1E protein alone in
      this study. The protective immunity was assessed with body weight gain, fecal
      oocyst output, detection of intestinal IgA positive cells and percentages of
      CD3(+), CD4(+) or CD8(+) intestinal intraepithelial lymphocytes (IELs). Chickens
      vaccinated with different doses of recombinant 3-1E protein plus AbISCO(r)-300
      showed higher percentages of CD3(+), CD4(+), and CD8(+) intestinal IELs,
      increased positive expression rate of intestinal IgA, increased body weight gains
      and decreased oocyst shedding compared with recombinant 3-1E protein-only
      vaccinated groups. The results showed that immunization with various doses of the
      recombinant 3-1E protein in AbISCO(r)-300 adjuvant enhanced immune protection
      against avian coccidiosis. 

PMID- 24675419
TI  - Selection of a human butyrylcholinesterase-like antibody single-chain variable
      fragment resistant to AChE inhibitors from a phage library expressed in E. coli.
AB  - Organophosphates are potent poisoning agents that cause severe cholinergic
      toxicity. Current treatment has been reported to be unsatisfactory and novel
      antidotes are needed. In this study, we used a single-chain variable fragment
      (scFv) library to select a recombinant antibody fragment (WZ1-14.2.1) with
      butyrylcholinesterase-like catalytic activity by using an innovative method
      integrating genetic selection and the bait-and-switch strategy. Ellman assay
      demonstrated that WZ1-14.2.1 has Michaelis-Menten kinetics in the hydrolysis of
      all the three substrates used, acetylthiocholine, propionylthiocholine and
      butyrylthiocholine. Notably, the catalytic activity was resistant to the
      following acetylcholinesterase inhibitors: neostigmine, iso-OMPA, chlorpyrifos
      oxon, dichlorvos, and paraoxon ethyl. Otherwise, the enzymatic activity of WZ1
      14.2.1 was inhibited by the selective butyrylcholinesterase inhibitor,
      ethopropazine, and by the Ser-blocking agent phenylmethanesuphonyl fluoride. A
      hypothetical 3D structure of the WZ1-14.2.1 catalytic site, compatible with
      functional results, is proposed on the basis of a molecular modeling analysis.

PMID- 24675420
TI  - Orchestration of cell surface proteins by Rab11.
AB  - The organization of cells into interconnected structures such as animal tissues
      requires a sophisticated system directing receptors and adhesion proteins to the
      cell surface. The Rab11 small G proteins (Rab11a, b, and Rab25) of the Ras
      superfamily are master regulators of the surface expression of receptors and
      adhesion proteins. Acting as a molecular switch, Rab11 builds distinct molecular
      machinery such as motor protein complexes and the exocyst to transport proteins
      to the cell surface. Recent evidence reveals Rab11 localization at the trans
      Golgi network (TGN), post-Golgi vesicles, and the recycling endosome, placing it
      at the intersection between the endocytic and exocytic trafficking pathways. We
      review Rab11 in various cellular contexts, and discuss its regulation and
      mechanisms by which Rab11 couples with effector proteins. 

PMID- 24675421
TI  - Retaining MKP1 expression and attenuating JNK-mediated apoptosis by RIP1 for
      cisplatin resistance through miR-940 inhibition.
AB  - The elucidation of chemoresistance mechanisms is important to improve cancer
      patient survival. In this report, we investigated the role and mechanism through
      which receptor-interacting protein 1 (RIP1), a mediator in cell survival and
      death signaling, participates in cancer's response to chemotherapy. In lung
      cancer cells, knockdown of RIP1 substantially increased cisplatin-induced
      apoptotic cytotoxicity, which was associated with robust JNK activation. The
      expression of the JNK inactivating phosphatase, MKP1, was substantially reduced
      in RIP1 knockdown cells. Although MKP1 protein stability was not altered by RIP1
      suppression, the synthesis rate of MKP1 was dramatically reduced in RIP1
      suppressed cells. Furthermore, we found that the expression of miR-940 was
      substantially increased in RIP1 knockdown cells. Knockdown of miR-940 restored
      MKP1 expression and attenuated cisplatin-induced JNK activation and cytotoxicity.
      Importantly, ectopic expression of MKP1 effectively attenuated cisplatin-induced
      JNK activation and cytotoxicity. In addition, activation of the JNK upstream
      signaling kinase, MKK4, was also potentiated in RIP1 knockdown cells. Altogether,
      our results suggest that RIP1 contributes to cisplatin resistance by suppressing
      JNK activation that involves releasing miR-940-mediated inhibition of MKP1 and
      suppressing activation of MKK4. Intervention targeting the RIP1/miR-940/MKP1/JNK
      pathway may be used to sensitize platinum-based chemotherapy. 

PMID- 24675423
TI  - Melittin suppresses EGF-induced cell motility and invasion by inhibiting
      PI3K/Akt/mTOR signaling pathway in breast cancer cells.
AB  - Bee venom is a natural compound produced by the honey bee (Apis mellifera), and
      has been reported as having the biological and pharmacological activities,
      including anti-bacterial, anti-viral and anti-inflammation. In the present study,
      the inhibitory effects of bee venom and its major peptide components on the tumor
      invasion were demonstrated. It was confirmed the inhibitory effects of bee venom,
      melittin, and apamin on the EGF-induced invasion of breast cancer cells.
      Transwell invasion and wound-healing assays showed that bee venom and melittin
      significantly inhibits the EGF-induced invasion and migration of breast cancer
      cells. Also, bee venom and melittin reduced the EGF-stimulated F-actin
      reorganization at the leading edge, but apamin did not affect. Particularly,
      melittin inhibited the EGF-induced MMP-9 expression via blocking the NF-kappaB
      and PI3K/Akt/mTOR pathway. In addition, melittin significantly suppressed the EGF
      induced FAK phosphorylation through inhibition of mTOR/p70S6K/4E-BP1 pathway.
      These results suggest that inhibitory effects of melittin on breast cancer cell
      motility and migration may be related to the inhibition of mTOR pathway. 

PMID- 24675422
TI  - Inhibitory effect of galangin on atopic dermatitis-like skin lesions.
AB  - Galangin is a member of the flavonol class of flavonoids having anti-inflammatory
      and anti-oxidative potential. Previously we reported the inhibitory effect of
      galangin on the mast cell-mediated allergic inflammation. For incremental
      research, we investigated the effects of galangin on atopic dermatitis (AD)-like
      skin lesions and underlying mechanisms of action. We established an atopic
      dermatitis model in BALB/c mice by repeated local exposure of house dust mite
      (Dermatophagoides farinae) extract (DFE) and 2,4-dinitrochlorobenzene (DNCB) to
      the ears. Repeated alternative treatment of DFE/DNCB caused AD-like skin lesions.
      Topical application of galangin reduced AD symptoms based on ear thickness and
      histopathological analysis, in addition to serum IgE and IgG2a levels. Galangin
      inhibited mast cell infiltration into the ear and serum histamine level. Galangin
      suppressed DFE/DNCB-induced expression of interleukin (IL)-4, IL-5, IL-13, IL-31,
      IL-32, and interferon (IFN)-gamma in the ear tissue. To define the underlying
      mechanisms of action, tumor necrosis factor-alpha/IFN-gamma-activated human
      keratinocytes (HaCaT) model was used. Galangin significantly inhibited the
      expression of cytokines and chemokine by the down-regulation of nuclear factor
      kappaB and mitogen-activated protein kinases in HaCaT cells. Taken together, the
      results demonstrate that galangin inhibited AD-like symptoms, suggesting that
      galangin might be a candidate for the treatment of AD. 

PMID- 24675425
TI  - Expression of a functional recombinant oleosin-human hyaluronidase hPH-20 fusion
      in Arabidopsis thaliana.
AB  - The use of plants as expression systems for the production of recombinant
      proteins has distinct advantages, such as safety, ease, low cost and high yields.
      A plant binary expression vector, pOTBar-hPH20, containing an oleosin-hPH20
      fusion gene and a Basta selection marker gene was constructed and introduced into
      Arabidopsis thaliana via the floral dip method. Transformed A. thaliana seed
      lines were obtained and analyzed by PCR. The PCR results indicated that oleosin
      hPH20 fusion gene was integrated into the A. thaliana genome. The oleosin-hPH20
      fusion protein was detected by SDS-PAGE and Western blot analysis. The oleosin
      hPH20 fusion protein was expressed and had good antigenicity in the transgenic A.
      thaliana seeds. An enzyme assay suggested that the recombinant oleosin-hPH20
      fusion protein had hyaluronidase activity. 

PMID- 24675424
TI  - Detection of termites and other insects consumed by African great apes using
      molecular fecal analysis.
AB  - The consumption of insects by apes has previously been reported based on direct
      observations and/or trail signs in feces. However, DNA-based diet analyses may
      have the potential to reveal trophic links for these wild species. Herein, we
      analyzed the insect-diet diversity of 9 feces obtained from three species of
      African great apes, gorilla (Gorilla gorilla gorilla), chimpanzee (Pan
      troglodytes) and bonobo (Pan paniscus), using two mitochondrial amplifications
      for arthropods. A total of 1056 clones were sequenced for Cyt-b and COI gene
      libraries, which contained 50 and 56 operational taxonomic units (OTUs),
      respectively. BLAST research revealed that the OTUs belonged to 32 families from
      5 orders (Diptera, Isoptera, Lepidoptera, Coleoptera, and Orthoptera). While ants
      were not detected by this method, the consumption of flies, beetles, moths,
      mosquitoes and termites was evident in these samples. Our findings indicate that
      molecular techniques can be used to analyze insect food items in wild animals. 

PMID- 24675426
TI  - Validation of microinjection methods for generating knockout mice by CRISPR/Cas
      mediated genome engineering.
AB  - The CRISPR/Cas system, in which the Cas9 endonuclease and a guide RNA
      complementary to the target are sufficient for RNA-guided cleavage of the target
      DNA, is a powerful new approach recently developed for targeted gene disruption
      in various animal models. However, there is little verification of microinjection
      methods for generating knockout mice using this approach. Here, we report the
      verification of microinjection methods of the CRISPR/Cas system. We compared
      three methods for injection: (1) injection of DNA into the pronucleus, (2)
      injection of RNA into the pronucleus, and (3) injection of RNA into the
      cytoplasm. We found that injection of RNA into the cytoplasm was the most
      efficient method in terms of the numbers of viable blastocyst stage embryos and
      full-term pups generated. This method also showed the best overall knockout
      efficiency. 

PMID- 24675428
TI  - Detection of erythrocytes in patients with Waldenstrom macroglobulinemia using
      atomic force microscopy.
AB  - The pathological changes of erythrocytes are detected at the nanometer scale,
      which is important for revealing the onset of diseases and diagnosis. The aim of
      this study is to examine the ultrastructural changes of erythrocytes in
      Waldenstrom macroglobulinemia (WM) at a nanometer scale. Blood samples were
      collected from two healthy volunteers, two WM patients, and three multiple
      myeloma (MM) patients when they were first diagnosed. The changes of morphology
      in the erythrocytes were studied at the nanometer level by high-resolution atomic
      force microscopy imaging (AFM). Compared with the healthy controls and the MM
      patients, there were dramatic deformations in the overall shape and surface
      membrane of the erythrocytes in WM patients. Healthy, pathological WM, and MM
      erythrocytes could be distinguished by several morphological parameters,
      including the width, length, length-to-width ratio, valley, peak, peak-to-valley,
      and Ra. AFM is able to detect the morphological differences in the red blood
      cells from WM patients, healthy controls, and MM patients. Therefore, the
      erythrocyte morphology is an important parameter for the diagnosis of WM, which
      can be used to distinguish WM from MM. The changes of ultrastructure in red blood
      cells may provide a clue to reveal the mechanism of WM. 

PMID- 24675427
TI  - Molecular insights into the membrane-associated phosphatidylinositol 4-kinase
      IIalpha.
AB  - Phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), a membrane-associated PI
      kinase, plays a central role in cell signalling and trafficking. Its kinase
      activity critically depends on palmitoylation of its cysteine-rich motif (-CCPCC
      ) and is modulated by the membrane environment. Lack of atomic structure impairs
      our understanding of the mechanism regulating kinase activity. Here we present
      the crystal structure of human PI4KIIalpha in ADP-bound form. The structure
      identifies the nucleotide-binding pocket that differs notably from that found in
      PI3Ks. Two structural insertions, a palmitoylation insertion and an RK-rich
      insertion, endow PI4KIIalpha with the 'integral' membrane-binding feature.
      Molecular dynamics simulations, biochemical and mutagenesis studies reveal that
      the palmitoylation insertion, containing an amphipathic helix, contributes to the
      PI-binding pocket and anchors PI4KIIalpha to the membrane, suggesting that
      fluctuation of the palmitoylation insertion affects PI4KIIalpha's activity. We
      conclude from our results that PI4KIIalpha's activity is regulated indirectly
      through changes in the membrane environment. 

PMID- 24675429
TI  - Simultaneous saccharification and fermentation of Eastern redcedar heartwood and
      sapwood using a novel size reduction technique.
AB  - This study investigated the effect of two wood zones (sapwood versus heartwood)
      and size reduction techniques [Crumbles(r) (Crumbles(r) is a registered trademark
      of Forest Concepts, LLC, Auburn, WA, USA) particles versus ground particles] on
      wood glucan-to-ethanol yield after acid bisulfite pretreatment and simultaneous
      saccharification and fermentation (SSF) of Eastern redcedar. SSFs were conducted
      at 8% solids loading (w/w dry basis) using Accellerase(r) 1500 at a loading of
      46FPU/g glucan and Saccharomyces cerevisiae D5A for ethanol fermentation. The
      size reduction technique had no effect on ethanol yield. However, sapwood glucan
      to-ethanol yields were significantly greater than heartwood yields. The highest
      wood glucan-to-ethanol yield of 187L/dryMg (95% of theoretical) was achieved with
      sapwood crumbled particles in 240h. Ground sapwood, crumbled heartwood and ground
      heartwood achieved ethanol yields of 89%, 81% and 80% of theoretical in 240h,
      respectively. Preliminary mass balances showed 100% glucan recovery with crumbled
      sapwood and extensive (72%) delignification. 

PMID- 24675430
TI  - Comparison between bougies and stylets for simulated tracheal intubation with the
      C-MAC D-blade videolaryngoscope.
AB  - BACKGROUND: The C-MAC D-blade is a new, highly angulated, videolaryngoscope blade
      designed for use in patients with difficult airways. Directing a tracheal tube
      into the trachea with any indirect viewing laryngoscope can be difficult, even
      with a good view of the laryngeal inlet. OBJECTIVE: To determine which
      introducing strategy is most suitable for use with the C-MAC D-blade
      videolaryngoscope. DESIGN: Observational manikin study. SETTING: Centre for
      Simulation and Patient Safety. PARTICIPANTS: Twenty-four anaesthetists of at
      least 12 months' of experience. INTERVENTIONS: Six tracheal tube introducer
      strategies (no tracheal tube introducer (TX); hockey stick stylet (SH); Gliderite
      stylet (SG); bougie with tube loaded distally, near its curved tip (BD); bougie
      with tube loaded proximally (BP); bougie unloaded until tracheal placement (BU))
      for each of two laryngoscopy settings (easy and difficult) in a SimMan 3G
      manikin. Two intubation attempts, with a maximum time allowance of 60 s each,
      were allowed for all laryngoscopy setting/introducer combinations. MAIN OUTCOME
      MEASURES: Time to intubate in seconds. Secondary outcome was overall subjective
      difficulty using a visual analogue scale. RESULTS: In the easy laryngoscopy
      setting, time to intubation was [median (interquartile range): SH 8.5 sec (7 to
      11); SG 10 (8 to 11.5); BD 11 (10 to 12.5); TX 11 (7 to 31.5); BP 12 (11 to
      13.5); BU 13 (11 to 14.5). There was no evidence of an overall difference in
      introducer strategies for time to intubate (P <  .025) with SG and SH found to be
      favourable when compared with BU, and SH was also favourable when compared with
      BP. In the difficult laryngoscopy setting, time to intubation was: SG 11.5 (10 to
      17.5); SH 14 (12 to 22); BD 15.5 (12 to 23.5); BU 16.5 (14 to 21); BP 16.5 (15.5
      to 20.5); TX 60 (26.5 to 60). There was evidence of an overall difference in
      introducer strategies for time to intubate (P < 0.025) with all introducers found
      to be favourable compared with TX. SG was found to be favourable when compared
      with BU and BP. In groups TX and SH, anaesthetists failed to intubate in 13 of 24
      cases and 1 of 24 cases, respectively. The visual analogue scores tended to
      reflect intubation times, more so in the difficult setting. CONCLUSION: The
      differences in time to intubate in both the easy and difficult laryngoscopy
      settings were minor for the different introducer strategies studied. The stylet
      introducers tended to take less time, but this did not result in important
      statistical differences. When using the C-MAC D-blade videolaryngoscope for
      simulated tracheal intubation, stylets and bougies performed in a similar
      fashion.

PMID- 24675431
TI  - In response.

PMID- 24675432
TI  - Re: Odate S, Shikata J, Yamamura S, et al. Extremely wide and asymmetric anterior
      decompression causes postoperative C5 palsy. Spine 2013; 38:2184-9.

PMID- 24675434
TI  - Structural signatures of (two) characteristic dynamical temperatures in lithium
      metasilicate.
AB  - We report on the dynamic and structural characterization of lithium metasilicate
      Li2SiO3, a network-forming ionic glass, by means of molecular dynamics
      simulations. The system is characterized by a network of SiO4 tetrahedra
      disrupted by Li ions which diffuse through the network. Measures of mean square
      displacement and the diffusion constant of Si and O atoms allow us to identify
      the mode-coupling temperature, Tc ~ 1500 K. At a much lower temperature, a change
      in the slope of the specific volume versus temperature singles out the glass
      transition at Tg ~ 1000 K, the temperature below which the system goes out of
      equilibrium. We find signatures of both dynamical temperatures in structural
      order parameters related to the orientation of the tetrahedra. At lower
      temperatures we find that a set of order parameters which measure the relative
      orientation of neighbouring tetrahedra cease to increase and stay constant below
      Tc. Nevertheless, the bond orientational order parameter, which in this system
      measures local tetrahedral order, is found to continue growing below Tc until Tg,
      below which it remains constant. Although these structural signatures of the two
      dynamical temperatures do not imply any real thermodynamic transition in terms of
      the order parameters, they do give insight into the relaxation processes that
      occur between Tc and Tg, in particular they allow us to characterize the nature
      of the crossover happening around Tc. 

PMID- 24675435
TI  - How is success or failure in river restoration projects evaluated? Feedback from
      French restoration projects.
AB  - Since the 1990s, French operational managers and scientists have been involved in
      the environmental restoration of rivers. The European Water Framework Directive
      (2000) highlights the need for feedback from restoration projects and for
      evidence-based evaluation of success. Based on 44 French pilot projects that
      included such an evaluation, the present study includes: 1) an introduction to
      restoration projects based on their general characteristics 2) a description of
      evaluation strategies and authorities in charge of their implementation, and 3) a
      focus on the evaluation of results and the links between these results and
      evaluation strategies. The results show that: 1) the quality of an evaluation
      strategy often remains too poor to understand well the link between a restoration
      project and ecological changes; 2) in many cases, the conclusions drawn are
      contradictory, making it difficult to determine the success or failure of a
      restoration project; and 3) the projects with the poorest evaluation strategies
      generally have the most positive conclusions about the effects of restoration.
      Recommendations are that evaluation strategies should be designed early in the
      project planning process and be based on clearly-defined objectives. 

PMID- 24675436
TI  - The gut microbiome in health and disease.

PMID- 24675437
TI  - Released plasmonic electric field of ultrathin tetrahedral-amorphous-carbon films
      coated Ag nanoparticles for SERS.
AB  - We have demonstrated the plasmonic characteristics of an ultrathin tetrahedral
      amorphous carbon (ta-C) film coated with Ag nanoparticles. The simulation result
      shows that, under resonant and non-resonant excitations, the strongest plasmonic
      electric field of 1 nm ta-C coated Ag nanoparticle is not trapped within the ta-C
      layer but is released to its outside surface, while leaving the weaker electric
      field inside ta-C layer. Moreover, this outside plasmonic field shows higher
      intensity than that of uncoated Ag nanoparticle, which is closely dependent on
      the excitation wavelength and size of Ag particles. These observations are
      supported by the SERS measurements. We expect that the ability for ultrathin ta-C
      coated Ag nanoparticles as the SERS substrates to detect low concentrations of
      target biomolecules opens the door to the applications where it can be used as a
      detection tool for integrated, on-chip devices.

PMID- 24675438
TI  - Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous
      wound healing in streptozotocin-induced diabetic rats.
AB  - Prolonged inflammation and increased oxidative stress impairs healing in
      diabetics and application of curcumin, a well known antioxidant and anti
      inflammatory agent, could be an important strategy in improving impaired healing
      in diabetics. So, the present study was conducted to evaluate the cutaneous wound
      healing potential of topically applied curcumin in diabetic rats. Open excision
      skin wound was created in streptozotocin induced diabetic rats and wounded rats
      were divided into three groups; i) control, ii) gel-treated and iii) curcumin
      treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were
      topically applied in the gel- and curcumin-treated groups, respectively, once
      daily for 19 days. Curcumin application increased the wound contraction and
      decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis
      factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin
      also increased the levels of anti-inflammatory cytokine i.e. IL-10 and
      antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione
      peroxidase. Histopathologically, the curcumin-treated wounds showed better
      granulation tissue dominated by marked fibroblast proliferation and collagen
      deposition, and wounds were covered by thick regenerated epithelial layer. These
      findings reveal that the anti-inflammatory and antioxidant potential of curcumin
      caused faster and better wound healing in diabetic rats and curcumin could be an
      additional novel therapeutic agent in the management of impaired wound healing in
      diabetics.

PMID- 24675439
TI  - The genotoxic effects of the imidacloprid-based insecticide formulation Glacoxan
      Imida on Montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).
AB  - The neonicotinoid insecticide imidacloprid (IMI) affects the insect central
      nervous system and is successfully applied to control pests for a variety of
      agricultural crops. In the current study, acute toxicity and genotoxicity of the
      IMI-containing commercial formulation insecticide Glacoxan Imida (35 percent IMI)
      was evaluated on Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed under
      laboratory conditions. A lethal effect was evaluated as the end point for
      lethality, whereas micronucleus (MN) frequency and DNA single-strand breaks
      evaluated by the single cell gel electrophoresis (SCGE) assay were employed as
      end points for genotoxicity. Sublethal end points were assayed within the 12.5
      37.5mg/L IMI concentration range. Experiments were performed on tadpoles at stage
      36 (range, 35-37) according to the classification proposed by Gosner. Lethality
      studies revealed an LC50 96h value of 52.622mg/L IMI. Increased frequency of MNs
      was only observed when 25.0mg/L was assayed for 96h, whereas no other nuclear
      abnormalities were induced. Increase of the genetic damage index was observed at
      48h of treatment within the 12.5-37.5mg/L concentration range, whereas an
      increased frequency of DNA damage was observed only in tadpoles treated with
      37.5mg/L IMI for 96h. This study represents the first evidence of the acute
      lethal and genotoxic effects exerted by IMI on tadpoles of an amphibian species
      native to Argentina under laboratory conditions. 

PMID- 24675440
TI  - Uptake of a cyanotoxin, beta-N-methylamino-L-alanine, by wheat (Triticum
      aestivum).
AB  - In order to study the uptake of the cyanobacterial neurotoxin beta-N-methylamino
      l-alanine (BMAA) into the crop plant Triticum aestivum during germination and
      primary growth imbibed grains and 7-day-old seedlings were irrigated with 100 and
      1000ug l(-1) BMAA for 4 days and 100ug l(-1) BMAA for 28 days. Content of
      derivatized free and protein-associated BMAA in seedlings, root and shoot tissue,
      respectively, were analyzed by LC-MS/MS. Free BMAA was only detected in seedlings
      exposed to 1000ug l(-1) BMAA, whereas protein-associated BMAA was found at both
      exposure concentrations. Irrigation with 100ugl(-1) BMAA led to an uptake of the
      neurotoxin into roots and shoots and to immediate protein-association. In roots,
      protein-associated BMAA was detectable after 5 days with peaking amounts after 14
      days. Longer exposure did not cause further accumulation in roots. In contrast,
      protein-associated BMAA was detected in shoot samples after only 1 day. In shoots
      the highest amounts of protein-associated BMAA were found after 28 days. In turn,
      in both plant compartments free BMAA was below the measurable concentration.

PMID- 24675441
TI  - Bioaccumulation of 210Po in common gastropod and bivalve species from the
      northern Gulf.
AB  - This study sets the baseline for the concentration of the natural-series
      radionuclide polonium-210 in two species of gastropods and four species of
      bivalves that are common to the Northern Arabian/Persian Gulf. (210)Po is
      primarily absorbed from water and via ingestion of detrital material by
      gastropoda and bivalves. This concentrated (210)Po can then be passed along to
      the next trophic level of the marine food web. The lowest (210)Po concentration
      was measured in the gastropod Stomatella auricular (10.36-12.39Bq kg(-1)dry) and
      the highest in the bivalve Marica marmorata (193.51-215.60Bq kg(-1)dry). The
      measured concentration factor for these molluscs in the northern Gulf varied
      between 4.8 and 115*10(3), values very similar to the IAEA recommended value for
      bivalves and gastropods of 2*10(4).

PMID- 24675442
TI  - Accumulation of hexabromocyclododecane diastereomers and enantiomers in two
      microalgae, Spirulina subsalsa and Scenedesmus obliquus.
AB  - Selective accumulation and bioisomerization of hexabromocyclododecane (HBCD)
      diastereomers and their enantiomers have been reported in several aquatic
      organisms; however, these processes have not been evaluated in algae. In the
      present study, the accumulation of three HBCD diastereomers (alpha-, beta- and
      gamma-HBCD) was studied using two microalgae, Spirulina subsalsa and Scenedesmus
      obliquus, in the plateau phase for seven days. The accumulation ability of S.
      obliquus was greater than that of S. subsalsa, with steady state BCF values in
      the range of 390-469 and 174-350, respectively. For the three diastereomers, the
      accumulation trend of alpha-HBCD>beta-HBCD>gamma-HBCD was observed in S.
      subsalsa, whereas the accumulation trend of beta-HBCD>alpha-HBCD>gamma-HBCD was
      observed in S. obliquus. Contrary to the process typically occurring in fish, the
      bioisomerization from beta- or gamma-HBCD to alpha-HBCD was not observed in
      algae. alpha-HBCD exhibited selective enrichment of (+)enantiomer in S. subsalsa
      and (-)enantiomer in S. obliquus. No significant enantioselectivity was observed
      for beta- and gamma-HBCD. New metabolites, tetrabromocyclododecadiene (TBCDi) and
      tribromocyclododecatriene (TriBCDie), were observed in S. subsalsa for the first
      time, but these were not observed in S. obliquus. 

PMID- 24675443
TI  - Ecological risk and pollution history of heavy metals in Nansha mangrove, South
      China.
AB  - Owing to the Industrial Revolution in the late 1970s, heavy metal pollution has
      been regarded as a serious threat to mangrove ecosystems in the region of the
      Pearl River Estuary, potentially affecting human health. The present study
      attempted to characterize the ecological risk of heavy metals (Cd, Cr, Cu, Mn,
      Ni, Pb and Zn) in Nansha mangrove, South China, by estimating their
      concentrations in the surface sediment. In addition, the pollution history of
      heavy metals was examined by determining the concentrations of heavy metals along
      the depth gradient. The phytoremediation potential of heavy metals by the
      dominant plants in Nansha mangrove, namely Sonneratia apetala and Cyperus
      malaccensis, was also studied. Results found that the surface sediment was
      severely contaminated with heavy metals, probably due to the discharge of
      industrial sewage into the Pearl River Estuary. Spatial variation of heavy metals
      was generally unobvious. The ecological risk of heavy metals was very high,
      largely due to Cd contamination. All heavy metals, except Mn, decreased with
      depth, indicating that heavy metal pollution has been deteriorating since 1979.
      Worse still, the dominant plants in Nansha mangrove had limited capability to
      remove the heavy metals from sediment. Therefore, we propose that immediate
      actions, such as regulation of discharge standards of industrial sewage, should
      be taken by the authorities concerned to mitigate the ecological risk posed by
      heavy metals. 

PMID- 24675444
TI  - Effect of lanthanum(III) on the production of ethylene and reactive oxygen
      species in soybean seedlings exposed to the enhanced ultraviolet-B radiation.
AB  - The enhanced ultraviolet-B (UV-B) radiation caused by ozone depletion may exert
      deleterious effects on plants. Therefore, studies on the effect of UV-B radiation
      on plants, as well as studies on the methods for alleviating the deleterious
      effects by chemical control, are of great significance. In this study, after
      soybean (Glycine max) seedlings were exposed to UV-B radiation (10.2 and 13.8kJ
      m(-2)day(-1)) for 5 days and the followed 6 days of restoration, respectively,
      the effects of 20mg L(-1) lanthanum (III) [La(III)] on leaf phenotype,
      photosynthetic rate, and production of ethylene and reactive oxygen species (ROS)
      were investigated. The results indicated that the exposure to 10.2 and 13.8kJ m(
      2)day(-1) UV-B radiation could cause injury to the leaf phenotype, and lead to
      the decrease in the content of chlorophyll and the net photosynthetic rate, and
      the increase in the contents of ROS, ethylene and 1-aminocyclopropanecarboxylic
      acid, and 1-aminocyclopropanecarboxylic acid synthase activity in soybean
      seedlings. Following the withdrawal of the enhanced UV-B radiation, the above
      mentioned parameters gradually recovered, and the recovery of soybean seedlings
      exposed to 10.2kJ m(-2)day(-1) UV-B radiation was faster than those in soybean
      seedlings exposed to 13.8kJ m(-2)day(-1) UV-B radiation. The leaf injury and the
      changes in the above indices that were induced by the enhanced UV-B radiation,
      especially at 10.2kJ m(-2)day(-1), were alleviated after the pretreatment of
      soybean seedlings with 20mg L(-1) La(III). The results of the correlation
      analysis demonstrated that the injury to the leaf phenotype and the decrease in
      the photosynthetic rate of soybean seedlings were correlated with the increase in
      the ROS content that was induced by ethylene in soybean seedlings. The
      pretreatment with 20mg L(-1) La(III) alleviated the injury caused by the enhanced
      UV-B radiation through the regulation of the ROS production.

PMID- 24675445
TI  - Teratogenic effects and monetary cost of selenium poisoning of fish in Lake
      Sutton, North Carolina.
AB  - Selenium pollution from coal ash wastewater was investigated in Lake Sutton, NC.
      This lake has been continuously used as a cooling pond for a coal-fired power
      plant since 1972. Historic and recent levels of contamination in fish tissues (14
      105ug Se/g dry weight in liver, 24-127 in eggs, 4-23 in muscle, 7-38 in whole
      body) exceeded toxic thresholds and teratogenic effects were observed in fish
      collected in 2013. A high proportion (28.9 percent) of juvenile Lepomis spp.
      exhibited spinal and craniofacial malformations that were consistent with
      selenium poisoning. Teratogenic Deformity Index values indicated population-level
      impacts on the fishery. The partially monetized cost of resultant fishery losses
      was calculated at over $US 8.6 million annually, and over $US 217 million for the
      entire period of damage, which dates back to 1987 when chemical and biological
      monitoring began.

PMID- 24675448
TI  - [Drug addiction: between classification and social and health policies].
AB  - Recent changes in Italian legislation about drug use suggest a reflection, in
      order to plan health policies useful to reducing the magnitude of the problem. On
      the one hand, the classification between soft and hard drugs is misleading: it is
      not the substance but the consumption habits that can be considered light or
      heavy. On the other hand, the adoption of strict regulations inattentive to harm
      reduction has not yielded positive results in terms of drug use spreading.
      Finally, the association between cannabis use and the onset of psychotic
      disorders deserve to be confirmed by further studies.

PMID- 24675446
TI  - Comprehensive analyses of ventricular myocyte models identify targets exhibiting
      favorable rate dependence.
AB  - Reverse rate dependence is a problematic property of antiarrhythmic drugs that
      prolong the cardiac action potential (AP). The prolongation caused by reverse
      rate dependent agents is greater at slow heart rates, resulting in both reduced
      arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates.
      The opposite property, forward rate dependence, would theoretically overcome
      these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain
      elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic
      property of perturbations to the AP. We have addressed the possibility of forward
      rate dependence by performing a comprehensive analysis of 13 ventricular myocyte
      models. By simulating populations of myocytes with varying properties and
      analyzing population results statistically, we simultaneously predicted the rate
      dependent effects of changes in multiple model parameters. An average of 40
      parameters were tested in each model, and effects on AP duration were assessed at
      slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD
      ionic current perturbations and generated specific predictions regarding their
      mechanisms. For instance, an increase in L-type calcium current is FRD when this
      is accompanied by indirect, rate-dependent changes in slow delayed rectifier
      potassium current. A comparison of predictions across models identified inward
      rectifier potassium current and the sodium-potassium pump as the two targets most
      likely to produce FRD AP prolongation. Finally, a statistical analysis of results
      from the 13 models demonstrated that models displaying minimal rate-dependent
      changes in AP shape have little capacity for FRD perturbations, whereas models
      with large shape changes have considerable FRD potential. This can explain
      differences between species and between ventricular cell types. Overall, this
      study provides new insights, both specific and general, into the determinants of
      AP duration rate dependence, and illustrates a strategy for the design of
      potentially beneficial antiarrhythmic drugs. 

PMID- 24675449
TI  - [Over diagnostic imaging in cardiology].
AB  - Medical imaging is one of the major cause of rising health care costs. Diagnostic
      imaging has increased more rapidly than any other component of medical care.
      About 5 billion imaging tests are performed worldwide each year. According to
      recent estimates, at least one-third of all examinations are partially or totally
      inappropriate. Two out of 3 imaging tests employ ionizing radiations with
      radiology or nuclear medicine. The medical use of radiation is the largest man
      made source of radiation exposure. Medical X-rays and gamma-rays are a proven
      human carcinogen. The attributable long-term extra-risk of cancer due to
      diagnostic testing is around 10% in industrialized countries. Cardiologists
      prescribe and/or directly perform >50% of all imaging examinations, accounting
      for about two-thirds of the total effective dose given to patients. The dose of
      common cardiological examinations may be significant: 500 chest X-rays= a stress
      scintigraphy with sestamibi, 750 chest X-rays= a Multislice Computed Tomography,
      1,000 chest X-rays= a coronary angiography and stenting. Unfortunately, few
      doctors are aware of the level of radiation their patients are exposed to during
      radiological tests and more intensive use of ionizing testing was not associated
      with greater awareness. Also as a consequence of unawareness, the rate of
      inappropriate examinations is unacceptably high in cardiology, even for
      procedures with high radiation load. Higher exposure doses correspond to higher
      long-term risks; there are no safe doses, and all doses add up in determining the
      cumulative risks over a lifetime. Doctors should make every effort so that "each
      patient should get the right imaging exam, at the right time, with the right
      radiation dose", as suggested by US Food and Drug Administration in the 2010
      initiative to reduce unnecessary radiation exposure from medical imaging. This is
      best obtained through a systematic implementation of the "3 A's strategy"
      proposed by the International Atomic Energy Agency in 2010: audit (of true
      delivered dose); appropriateness (since at least one-third of examinations are
      inappropriate); awareness (since the knowledge of doses and risks is largely).
      The regular application of "3 A's strategy" is usually not facilitated by a
      health system that pays for volumes, not for appropriateness. 

PMID- 24675450
TI  - [Complete diagnostic work-up provides the rational basis for the most appropriate
      therapy of myelodysplastic syndromes].
AB  - Myelodysplastic syndromes are now classified according to the 2008 World Health
      Organization criteria. An accurate risk assessment requires a keen evaluation of
      disease-related factors to adapt treatment to patients age, expectations and
      comorbidities. A high proportion of MDS patients are not eligible for potentially
      curative and consequently intensive treatment because of advanced age and/or
      clinically relevant comorbidities and poor performance status. In these patients,
      a number of new agents are available or being developed but their use should be
      carefully guided by the chromosomal and genetic determinant of the disease. 

PMID- 24675451
TI  - [Morphology: a critical phase in the diagnosis of myelodysplastic syndromes].
AB  - Diagnosis and classification of myelodysplastic syndromes (MDS) are based on the
      integration of morphology, immunophenotype, histology, genetics and molecular
      analysis. The role of cytomorphology in this context, however, remains
      fundamental and preliminary to the application of the other methods. The first
      modern classification of MDS, originally published by the FAB (French-American
      British) Group in 1985, was based on the recognition of five different diagnostic
      categories. The more recent 2008 WHO classification of hematopoietic neoplasms
      has widened and modified the FAB approach, by including seven different
      cytomorphological entities and decreasing the threshold of the blast cell
      percentage to 19% for the discrimination of MDS from acute myeloid leukemias. In
      addition, chronic myelomonocytic leukemia is now included in the new group or
      MDS/myeloproliferative neoplasms. Finally, precise quantitative and qualitative
      criteria are provided, with the aim to improve microscope method standardization.

PMID- 24675453
TI  - [The network between hematological centers for the standardization of
      myelodysplastic syndromes diagnosis].
AB  - A network of hematological centers specialized in the study of myelodysplastic
      syndromes (MDS) may be a useful tool for the standardization of the diagnosis of
      this heterogeneous group of hematologic syndromes and possibly provide not only
      biological but also epidemiological information. In each center included in the
      network the diagnosis of MDS will be performed according to criteria of WHO 2008
      classification and the last recommendations published by European LeukemiaNet in
      2013. In detail the following analyses will be carried out: morphological
      examination, bone marrow biopsy, conventional cytogenetic and possibly molecular
      cytogenetic studies. In each region will be identified a reference center that
      will collect data on all patients with suspected MDS creating a database with
      clinical, morphological and molecular-cytogenetic information. In particular, the
      morphological evaluation will be carried out in collaboration between the
      peripheral centers and the regional reference center through the sharing of
      images from slides. The collaboration between experts hematologists will allow
      the formulation of more precise diagnosis. Moreover, the national network for the
      standardization of MDS diagnosis could facilitate the ideation of new research
      projects and the identification of new prognostic markers. 

PMID- 24675452
TI  - [Diagnosis and prognosis in myelodysplastic syndromes. The impact of
      cytogenetics].
AB  - Diagnosis of myelodysplastic syndromes (MDS) is based on cytopenia(s), bone
      marrow morphology, and cytogenetics. Cytogenetics is helpful both to assess
      clonality and to identify typical aberrations. Chromosomal rearrangements are
      usually investigated through the karyotype after chromosome banding. Further
      insights may be obtained from higher resolution genome technologies, such as FISH
      and SNP arrays. One distinct clinico-pathologic entity diagnosed by the presence
      of an isolated deletion at chromosome 5q, so-called MDS with isolated del(5q),
      has been included in the WHO 2008 classification. Cytogenetics is also necessary
      to calculate prognostic scores at diagnosis of MDS. Chromosome abnormalities
      predict both survival and MDS evolution to acute myeloid leukemia. 

PMID- 24675454
TI  - [Molecular biology in myelodysplastic syndromes and acute myeloid leukemias
      "smoldering"].
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic
      disorders of the myeloid lineage characterized by peripheral cytopenias and
      frequent leukemic evolution. MDS differ for clinical presentation, disease
      behavior and progression and this is the reflection of remarkable variability at
      molecular level. To this moment disease diagnosis is still dependent on bone
      marrow morphology that, although high concordance rates among experts are
      reported, remains subjective. Karyotype analysis is mandatory but diagnosis may
      be difficult in presence of normal karyotype or non-informative cytogenetics.
      Standardized molecular markers are needed to better define diagnosis, prediction
      of disease progression and prognosis. Furthermore, a molecular biology analysis
      could provide an important therapeutic tool towards tailored therapy and new
      insights in the disease's biology. 

PMID- 24675455
TI  - [The role of iron metabolism in myelodysplastic syndromes].
AB  - Patients affected by myelodysplastic syndromes (MDS) with transfusion-dependent
      anemia are destined to develop iron overload. The main diagnostic tools for the
      diagnosis of transfusional iron overload are serum ferritin and transfusion
      history. In MDS several studies showed that iron overload is an independent
      negative prognostic factor. Deferasirox, an oral iron chelator, has shown
      efficacy and acceptable tolerability in MDS setting, and has also been shown to
      improve peripheral cytopenia in 10-20% of patients. Iron chelation therapy is
      recommended, after the transfusion of 20 red cell units, in low-risk MDS
      patients, and also in high-risk patients responding to treatment of the disease
      and/or candidates to receive allogeneic hematopoietic stem cell transplantation. 

PMID- 24675456
TI  - [Identification of myelodysplastic syndromes patients].
AB  - Myelodysplastic syndromes (MDS) are an heterogeneous group of hematological
      malignancies characterized by ineffective hematopoiesis and peripheral
      cytopenias, with a variable risk of developing acute myeloid leukemia. An
      accurate diagnosis is the basis of the possible selection of the most appropriate
      therapy. The most important parameters for an accurate prognosis and therapy are
      the biological characteristics of the disease, the clinical presentation, the
      fragility of the patient and the presence of comorbidities. MDS are mainly
      geriatric diseases and the presence of comorbidities and patient's poor
      performance status adversely affect the prognosis. Our group has proposed a
      system to identify the patients who have low probabilities to achieve benefit
      from treatment with azacitidine. A number of validated prognostic scores exist in
      MDS. The most widely used, although dated, is the International Prognostic
      Scoring System (IPSS). On IPSS scores we still base therapeutic choices. Recently
      a revised IPSS has been built on a larger cohort of patients still to be further
      validated, also in MDS treated patients. We at present can predict response to
      azacitidine and survival in patients treated with this drug. The goals of MDS
      therapy are for low-risk patients: improving quality of life through the
      improvement of hematopoiesis and for high risk patients: prolong survival and
      delay progression to acute myeloid leukemia. Currently, according to the
      calculated IPSS risk of the patient, age, biological parameters and comorbidities
      we may propose individualized therapies, which may vary from watch-and-wait to
      hypomethylating agent therapy, to an allogeneic transplant. Moreover, the new
      concept of sequential lines of therapy has gained consideration. 

PMID- 24675457
TI  - [Medicine and literature: an anthology].

PMID- 24675458
TI  - Cav-1 deletion impaired hematopoietic stem cell function.
AB  - A tightly controlled balance between hematopoietic stem and progenitor cell
      compartments is required to maintain normal blood cell homeostasis throughout
      life, and this balance is regulated by intrinsic and extrinsic cellular factors.
      Cav-1 is a 22-kDa protein that is located in plasma membrane invaginations and is
      implicated in regulating neural stem cell and embryonic stem cell proliferation.
      However, the role of Cav-1 in hematopoietic stem cell (HSC) function is largely
      unknown. In this study, we used Cav-1(-/-) mice to investigate the role of Cav-1
      in HSCs function during aging. The results showed that Cav-1(-/-) mice displayed
      a decreased percentage of B cells and an increased percentage of M cells in the
      bone marrow and peripheral blood, and these changes were due to an increased
      number of HSCs. FACS analysis showed that the numbers of Lin(-)Sca1(+)c-kit(+)
      cells (LSKs), long-term HSCs (LT-HSCs), short-term HSCs and multipotent
      progenitors were increased in Cav-1(-/-) mice compared with Cav-1(+/+) mice, and
      this increase became more pronounced with aging. An in vitro clonogenic assay
      showed that LT-HSCs from Cav-1(-/-) mice had reduced ability to self-renew.
      Consistently, an in vivo competitive transplantation assay showed that Cav-1(-/-)
      mice failed to reconstitute hematopoiesis. Moreover, a Cav-1 deletion disrupted
      the quiescence of LSKs and promoted cell cycle progression through G2/M phase. In
      addition, we found that Cav-1 deletion impaired the ability of HSCs to
      differentiate into mature blood cells. Taken together, these data suggest that
      Cav-1-deficient cells impaired HSCs quiescence and induced environmental
      alterations, which limited HSCs self-renewal and function. 

PMID- 24675459
TI  - p53 Induces skin aging by depleting Blimp1+ sebaceous gland cells.
AB  - p53 is an important inducer of organismal aging. However, its roles in the aging
      of skin remain unclear. Here we show that mice with chronic activation of p53
      develop an aging phenotype in the skin associated with a reduction of
      subcutaneous fat and loss of sebaceous gland (SG). The reduction in the fat layer
      may result from the decrease of mammalian TOR complex 1 (mTORC1) activity
      accompanied by elevated expression of energy expenditure genes, and possibly as
      compensatory effects, leading to the elevation of peroxisome proliferator
      activated receptor (PPAR)gamma, an inducer of sebocyte differentiation. In
      addition, Blimp1(+) sebocytes become depleted concomitantly with an increase in
      cellular senescence, which can be reversed by PPARgamma antagonist (BADGE)
      treatment. Therefore, our results indicate that p53-mediated aging of the skin
      involves not only thinning through the loss of subdermal fat, but also xerosis or
      drying of the skin through declining sebaceous gland activity. 

PMID- 24675460
TI  - Differential activity of GSK-3 isoforms regulates NF-kappaB and TRAIL- or
      TNFalpha induced apoptosis in pancreatic cancer cells.
AB  - While TRAIL is a promising anticancer agent due to its ability to selectively
      induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal
      adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for
      TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell
      lines is enhanced by pharmacological inhibition of glycogen synthase kinase-3
      (GSK-3) or by shRNA-mediated depletion of either GSK-3alpha or GSK-3beta. In
      contrast, depletion of GSK-3beta, but not GSK-3alpha, sensitized PDA cell lines
      to TNFalpha-induced cell death. Further experiments demonstrated that TNFalpha
      stimulated IkappaBalpha phosphorylation and degradation as well as p65 nuclear
      translocation were normal in GSK-3beta-deficient MEFs. Nonetheless, inhibition of
      GSK-3beta function in MEFs or PDA cell lines impaired the expression of the NF
      kappaB target genes Bcl-xL and cIAP2, but not IkappaBalpha. Significantly, the
      expression of Bcl-xL and cIAP2 could be reestablished by expression of GSK-3beta
      targeted to the nucleus but not GSK-3beta targeted to the cytoplasm, suggesting
      that GSK-3beta regulates NF-kappaB function within the nucleus. Consistent with
      this notion, chromatin immunoprecipitation demonstrated that GSK-3 inhibition
      resulted in either decreased p65 binding to the promoter of BIR3, which encodes
      cIAP2, or increased p50 binding as well as recruitment of SIRT1 and HDAC3 to the
      promoter of BCL2L1, which encodes Bcl-xL. Importantly, depletion of Bcl-xL but
      not cIAP2, mimicked the sensitizing effect of GSK-3 inhibition on TRAIL-induced
      apoptosis, whereas Bcl-xL overexpression ameliorated the sensitization by GSK-3
      inhibition. These results not only suggest that GSK-3beta overexpression and
      nuclear localization contribute to TNFalpha and TRAIL resistance via anti
      apoptotic NF-kappaB genes such as Bcl-xL, but also provide a rationale for
      further exploration of GSK-3 inhibitors combined with TRAIL for the treatment of
      PDA. 

PMID- 24675461
TI  - SKLB-163, a new benzothiazole-2-thiol derivative, exhibits potent anticancer
      activity by affecting RhoGDI/JNK-1 signaling pathway.
AB  - Small-molecule inhibitors are an attractive therapeutic approach for most types
      of human cancers. SKLB-163, a novel benzothiazole-2-thiol derivative, was
      developed via computer-aided drug design and de novo synthesis. MTT assay showed
      it had potent anti-proliferative activity on various human cancer cells.
      Treatment of cancer cells with SKLB-163 induced obvious apoptosis and inhibited
      proliferation in vitro. SKLB-163 administered p.o. showed a marked antitumor
      activity in vivo. Proteomic techniques were employed to identify possible drug
      target proteins. The data showed molecular mechanism of action might be involved
      in downregulation of RhoGDI, which finally contributed to increased apoptosis and
      inhibited proliferation. These findings provided the potential value of SKLB-163
      as a novel candidate antitumor drug. 

PMID- 24675462
TI  - MiR-19a/b modulate the metastasis of gastric cancer cells by targeting the tumour
      suppressor MXD1.
AB  - The microRNAs 19a and 19b, hereafter collectively referred to as miR-19a/b, were
      recognised to be the most important miRNAs in the oncomiRs-miR-17-92 cluster.
      However, the exact roles of miR-19a/b in cancers have not been elucidated. In the
      present study, miR-19a/b was found to be over-expressed in gastric cancer tissues
      and significantly associated with the patients' metastasis of gastric cancer.
      Using gain or loss-of-function in in vitro and in vivo experiments, a pro
      metastatic function of miR-19a/b was observed in gastric cancer. Furthermore,
      reporter gene assay and western blot showed that MXD1 is a direct target of miR
      19a/b. Functional assays showed that not only MXD1 had an opposite effect to miR
      19a/b in the regulation of gastric cancer cells, but also overexpression of MXD1
      reduced both miR-19a/b and c-Myc levels, indicating a potential positive feedback
      loop among miR-19a/b, MXD1 and c-Myc. In conclusion, miR-17-92 cluster members
      miR-19a/b facilitated gastric cancer cell migration, invasion and metastasis
      through targeting the antagonist of c-Myc -- MXD1, implicating a novel mechanism
      for the malignant phenotypes of gastric cancer. 

PMID- 24675463
TI  - Temozolomide resistance in glioblastoma cells occurs partly through epidermal
      growth factor receptor-mediated induction of connexin 43.
AB  - Glioblastoma Multiforme (GBM) is an aggressive adult primary brain tumor with
      poor prognosis. GBM patients develop resistance to the frontline chemotherapy,
      temozolomide (TMZ). As the connexins (Cx) have been shown to have a complex role
      in GBM, we investigated the role of Cx43 in TMZ resistance. Cx43 was increased in
      the TMZ-resistant low passage and cell lines. This correlated with the data in
      The Cancer Genome Atlas. Cx43 knockdown, reporter gene assays, chromatin
      immunoprecipitation assay, real-time PCR and western blots verified a role for
      Cx43 in TMZ resistance. This occurred by TMZ-resistant GBM cells being able to
      activate epidermal growth factor receptor (EGFR). In turn, EGFR activated the JNK
      ERK1/2-AP-1 axis to induce Cx43. The increased Cx43 was functional as indicated
      by gap junctional intercellular communication among the resistant GBM cells. Cell
      therapy could be a potential method to deliver drugs, such as anti-EGF to tumor
      cells. Similar strategies could be used to reverse the expression of Cx43 to
      sensitize GBM cells to TMZ. The studies showed the potential for targeting EGF in
      immune therapy. These agents can be used in conjunction with stem cell therapy to
      treat GBM. 

PMID- 24675464
TI  - Rapamycin delays salivary gland atrophy following ductal ligation.
AB  - Salivary gland atrophy is a frequent consequence of head and neck cancer
      irradiation therapy but can potentially be regulated through the mammalian target
      of rapamycin (mTOR). Excretory duct ligation of the mouse submandibular gland
      provokes severe glandular atrophy causing activation of mTOR. This study aims to
      discover the effects of blocking mTOR signaling in ligation-induced atrophic
      salivary glands. Following 1 week of unilateral submandibular excretory duct
      ligation: gland weights were significantly reduced, 4E-BP1 and S6rp were
      activated, and tissue morphology revealed typical signs of atrophy. However, 3
      days following ligation with rapamycin treatment, a selective mTOR inhibitor,
      gland weights were maintained, 4E-BP1 and S6rp phosphorylation was inhibited, and
      there were morphological signs of recovery from atrophy. However, following 5 and
      7 days of ligation and rapamycin treatment, glands expressed active mTOR and
      showed signs of considerable atrophy. This evidence suggests that inhibition of
      mTOR by rapamycin delays ligation-induced atrophy of salivary glands. 

PMID- 24675466
TI  - Arginine vasopressin neuronal loss results from autophagy-associated cell death
      in a mouse model for familial neurohypophysial diabetes insipidus.
AB  - Familial neurohypophysial diabetes insipidus (FNDI) characterized by progressive
      polyuria is mostly caused by mutations in the gene encoding neurophysin II
      (NPII), which is the carrier protein of the antidiuretic hormone, arginine
      vasopressin (AVP). Although accumulation of mutant NPII in the endoplasmic
      reticulum (ER) could be toxic for AVP neurons, the precise mechanisms of cell
      death of AVP neurons, reported in autopsy studies, remain unclear. Here, we
      subjected FNDI model mice to intermittent water deprivation (WD) in order to
      promote the phenotypes. Electron microscopic analyses demonstrated that, while
      aggregates are confined to a certain compartment of the ER in the AVP neurons of
      FNDI mice with water access ad libitum, they were scattered throughout the
      dilated ER lumen in the FNDI mice subjected to WD for 4 weeks. It is also
      demonstrated that phagophores, the autophagosome precursors, emerged in the
      vicinity of aggregates and engulfed the ER containing scattered aggregates.
      Immunohistochemical analyses revealed that expression of p62, an adapter protein
      between ubiquitin and autophagosome, was elicited on autophagosomal membranes in
      the AVP neurons, suggesting selective autophagy induction at this time point.
      Treatment of hypothalamic explants of green fluorescent protein (GFP)-microtubule
      associated protein 1 light chain 3 (LC3) transgenic mice with an ER stressor
      thapsigargin increased the number of GFP-LC3 puncta, suggesting that ER stress
      could induce autophagosome formation in the hypothalamus of wild-type mice as
      well. The cytoplasm of AVP neurons in FNDI mice was occupied with vacuoles in the
      mice subjected to WD for 12 weeks, when 30-40% of AVP neurons are lost. Our data
      thus demonstrated that autophagy was induced in the AVP neurons subjected to ER
      stress in FNDI mice. Although autophagy should primarily be protective for
      neurons, it is suggested that the organelles including ER were lost over time
      through autophagy, leading to autophagy-associated cell death of AVP neurons. 

PMID- 24675465
TI  - Resveratrol protects astrocytes against traumatic brain injury through inhibiting
      apoptotic and autophagic cell death.
AB  - Traumatic brain injury (TBI) is often caused by accidents that damage the brain.
      TBI can induce glutamate excitotoxicity and lead to neuronal and glial cell
      death. In this study, we investigated the mechanism of cell death during the
      secondary damage caused by TBI in vivo and in vitro, as well as the protective
      effect of resveratrol (RV). Here we report that glycogen synthase kinase-3beta
      (GSK-3beta) activation and microtubule-associated protein light chain 3
      processing were induced in rat brains exposed to TBI. In the in vitro TBI model,
      apoptotic and autophagic cell death were induced through glutamate-mediated GSK
      3beta activation in normal CTX TNA2 astrocytes. The GSK-3beta inhibitor SB216763
      or transfection of GSK-3beta small-interfering RNA increases cell survival. By
      contrast, overexpression of GSK-3beta enhanced glutamate excitotoxicity.
      Administration of RV reduced cell death in CTX TNA2 astrocytes by suppressing
      reactive oxygen species (ROS)-mediated GSK-3beta activation, the mechanism by
      which RV also exerted protective effects in vivo. Mitochondrial damages,
      including the opening of mitochondrial permeability transition pore (MPTP) and
      mitochondrial depolarization, were induced by glutamate through the ROS/GSK-3beta
      pathway. Moreover, cyclosporine A, an MPTP inhibitor, suppressed mitochondrial
      damage and the percentages of cells undergoing autophagy and apoptosis and
      thereby increased cell survival. Taken together, our results demonstrated that
      cell death occurring after TBI is induced through the ROS/GSK-3beta/mitochondria
      signaling pathway and that administration of RV can increase cell survival by
      suppressing GSK-3beta-mediated autophagy and apoptosis. Therefore, the results
      indicated that resveratrol may serve as a potential therapeutic agent in the
      treatment of TBI. 

PMID- 24675467
TI  - Targeting of preexisting and induced breast cancer stem cells with trastuzumab
      and trastuzumab emtansine (T-DM1).
AB  - The antibody trastuzumab (Herceptin) has substantially improved overall survival
      for patients with aggressive HER2-positive breast cancer. However, about 70% of
      all treated patients will experience relapse or disease progression. This may be
      related to an insufficient targeting of the CD44(high)CD24(low) breast cancer
      stem cell subset, which is not only highly resistant to chemotherapy and
      radiotherapy but also a poor target for trastuzumab due to low HER2 surface
      expression. Hence, we explored whether the new antibody-drug conjugate T-DM1,
      which consists of the potent chemotherapeutic DM1 coupled to trastuzumab, could
      improve the targeting of these tumor-initiating or metastasis-initiating cells.
      To this aim, primary HER2-overexpressing tumor cells as well as HER2-positive and
      HER2-negative breast cancer cell lines were treated with T-DM1, and effects on
      survival, colony formation, gene and protein expression as well as antibody
      internalization were assessed. This revealed that CD44(high)CD24(low)HER2(low)
      stem cell-like breast cancer cells show high endocytic activity and are thus
      particularly sensitive towards the antibody-drug conjugate T-DM1. Consequently,
      preexisting CD44(high)CD24(low) cancer stem cells were depleted by concentrations
      of T-DM1 that did not affect the bulk of the tumor cells. Likewise, colony
      formation was efficiently suppressed. Moreover, when tumor cells were cocultured
      with natural killer cells, antibody-dependent cell-mediated cytotoxicity was
      enhanced, and EMT-mediated induction of stem cell-like properties was prevented
      in differentiated tumor cells. Thus our study reveals an unanticipated targeting
      of stem cell-like breast cancer cells by T-DM1 that may contribute to the
      clinical efficacy of this recently approved antibody-drug conjugate. 

PMID- 24675468
TI  - Neuroprotective effect of osmotin against ethanol-induced apoptotic
      neurodegeneration in the developing rat brain.
AB  - Fetal alcohol syndrome is a neurological and developmental disorder caused by
      exposure of developing brain to ethanol. Administration of osmotin to rat pups
      reduced ethanol-induced apoptosis in cortical and hippocampal neurons. Osmotin, a
      plant protein, mitigated the ethanol-induced increases in cytochrome c, cleaved
      caspase-3, and PARP-1. Osmotin and ethanol reduced ethanol neurotoxicity both in
      vivo and in vitro by reducing the protein levels of cleaved caspase-3,
      intracellular [Ca(2+)]cyt, and mitochondrial transmembrane potential collapse,
      and also upregulated antiapoptotic Bcl-2 protein. Osmotin is a homolog of
      adiponectin, and it controls energy metabolism via phosphorylation. Adiponectin
      can protect hippocampal neurons against ethanol-induced apoptosis. Abrogation of
      signaling via receptors AdipoR1 or AdipoR2, by transfection with siRNAs, reduced
      the ability of osmotin and adiponectin to protect neurons against ethanol-induced
      neurodegeneration. Metformin, an activator of AMPK (adenosine monophosphate
      activated protein kinase), increased whereas Compound C, an inhibitor of AMPK
      pathway, reduced the ability of osmotin and adiponectin to protect against
      ethanol-induced apoptosis. Osmotin exerted its neuroprotection via Bcl-2 family
      proteins and activation of AMPK signaling pathway. Modulation of AMPK pathways by
      osmotin, adiponectin, and metformin hold promise as a preventive therapy for
      fetal alcohol syndrome. 

PMID- 24675469
TI  - Depletion of pre-mRNA splicing factor Cdc5L inhibits mitotic progression and
      triggers mitotic catastrophe.
AB  - Disturbing mitotic progression via targeted anti-mitotic therapy is an attractive
      strategy for cancer treatment. Therefore, the exploration and elucidation of
      molecular targets and pathways in mitosis are critical for the development of
      anti-mitotic drugs. Here, we show that cell division cycle 5-like (Cdc5L), a pre
      mRNA splicing factor, is a regulator of mitotic progression. Depletion of Cdc5L
      causes dramatic mitotic arrest, chromosome misalignments and sustained activation
      of spindle assembly checkpoint, eventually leading to mitotic catastrophe.
      Moreover, these defects result from severe impairment of kinetochore-microtubule
      attachment and serious DNA damage. Genome-wide gene expression analysis reveals
      that Cdc5L modulates the expression of a set of genes involved in the mitosis and
      the DNA damage response. We further found that the pre-mRNA splicing efficiency
      of these genes were impaired when Cdc5L was knocked down. Interestingly, Cdc5L is
      highly expressed in cervical tumors and osteosarcoma. Finally, we demonstrate
      that downregulation of Cdc5L decreases the cell viability of related tumor cells.
      These results suggest that Cdc5L is a key regulator of mitotic progression and
      highlight the potential of Cdc5L as a target for cancer therapy. 

PMID- 24675470
TI  - Inhibition of human mitochondrial peptide deformylase causes apoptosis in c-myc
      overexpressing hematopoietic cancers.
AB  - Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the
      mitochondrial membrane, reduces mitochondrial protein translation and causes
      apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels
      were overexpressed in cancer cells and primary acute myeloid leukemia samples.
      Myc regulates mitochondria and metabolism; we also demonstrated c-myc regulated
      the expression of HsPDF, likely indirectly. Inhibition of HsPDF by actinonin
      blocked mitochondrial protein translation and caused apoptotic death of myc
      positive Burkitt's lymphoma, but not myc-negative B cells. Inhibition of
      mitochondrial translation by chloramphenicol or tetracycline, structurally
      different inhibitors of the mitochondrial ribosome, which is upstream of
      deformylase activity, followed by treatment with actinonin, resulted in reversal
      of the biochemical events and abrogation of the apoptosis induced by actinonin.
      This reversal was specific to inhibitors of HsPDF. Inhibition of HsPDF resulted
      in a mitochondrial unfolded protein response (increased transcription factors
      CHOP and CEB/P and the mitochondrial protease Lon), which may be a mechanism
      mediating cell death. Therefore, HsPDF may be a therapeutic target for these
      hematopoietic cancers, acting via a new mechanism. 

PMID- 24675471
TI  - Essential role of PH domain and leucine-rich repeat protein phosphatase 2 in Nrf2
      suppression via modulation of Akt/GSK3beta/Fyn kinase axis during oxidative
      hepatocellular toxicity.
AB  - Instances of sustained oxidative activity have been shown to involve
      dysregulation of Nrf2-mediated transcriptional induction; however, mechanisms
      warranting Nrf2-repression remain unclear. In this study, using primary rat
      hepatocytes, we have attempted to identify factors that may negatively influence
      Nrf2 survival pathway. Though studies indicate a conspicuous association between
      Akt and Nrf2, a confirmatory link between the two is unaddressed. On inhibiting
      PI3K/Akt pathway, we observed compromised activities of antioxidant and
      detoxification enzymes culminating in oxidative cytotoxicity. This was
      accompanied by reduced nuclear retention of Nrf2 and its ARE binding affinity,
      increased Nrf2 ubiquitination and concurrent decline in its downstream targets.
      Moreover, Akt inhibition enhanced nuclear translocation as well as
      phosphorylation of Fyn kinase, an enzyme linked to Nrf2 degradation, by relieving
      GSK3beta from phosphorylation-mediated repression. The involvement of Akt and Fyn
      kinase in influencing Nrf2 signaling was further confirmed in oxidatively
      stressed hepatocytes by using tert-butyl hydroperoxide (tBHP). tBHP-induced
      decrease in Nrf2 levels was associated with enhanced Fyn kinase phosphorylation,
      Fyn kinase nuclear translocation and decreased levels of phosphorylated
      GSK3beta(Ser9) in a time-dependent manner. Interestingly, tBHP induced site
      specific deactivation of Akt as only Akt(Ser473) phosphorylation was observed to
      be affected. Further, protein expression as well as nuclear localization of
      PHLPP2, a phosphatase specific for Akt(Ser473), was found to be significantly
      enhanced in tBHP-stressed hepatocytes. Silencing of PHLPP2 not only resulted in
      considerable restoration of Nrf2 signaling, enhanced Nrf2-ARE binding and reduced
      Nrf2 ubiquitination but also significantly suppressed tBHP-induced ROS generation
      and alterations in mitochondrial permeability. We infer that cellular PHLPP2
      levels may aggravate oxidative toxicity by suppressing Nrf2/ARE transcriptional
      regulation via Akt(Se473)/GSK3beta/Fyn kinase axis. The study indicates that
      PHLPP2 could serve as a new target for developing strategies to manage
      pathological conditions exacerbated due to oxidative stress. 

PMID- 24675472
TI  - Survivin is essential for fertile egg production and female fertility in mice.
AB  - Survivin is the smallest member of the inhibitor of apoptosis protein (IAP)
      family and acts as a bifunctional protein involved in mitosis regulation and
      apoptosis inhibition. To identify the physiological role of Survivin in female
      reproduction, we selectively disrupted Survivin expression in oocytes and
      granulosa cells (GCs), two major cell types in the ovary, by two different Cre
      Loxp conditional knockout systems, and found that both led to defective female
      fertility. Survivin deletion in oocytes did not affect oocyte growth, viability
      and ovulation, but caused tetraploid egg production and thus female infertility.
      Further exploration revealed that Survivin was essential for regulating proper
      meiotic spindle organization, spindle assembly checkpoint activity, timely
      metaphase-to-anaphase transition and cytokinesis. Mutant mice with Survivin
      depleted in GCs showed reduced ovulation and subfertility, caused by defective
      follicular growth, increased follicular atresia and impaired luteinization. These
      findings suggest that Survivin has an important role in regulating
      folliculogenesis and oogenesis in the adult mouse ovary. 

PMID- 24675473
TI  - The incidence of ulcerative colitis (1995-2011) and Crohn's disease (1995-2012) -
      based on nationwide Danish registry data.
AB  - BACKGROUND AND AIMS: The incidence of ulcerative colitis (UC) and Crohn's disease
      (CD) has increased during the 20th century in North America and Western Europe.
      However, there are conflicting reports whether the incidence has declined,
      stabilized or even continued to increase. No nationwide Danish data on the
      incidence of UC and CD exist after 1992, and therefore we studied the incidence
      of UC (1995 through 2011) and CD (1995 through 2012). METHODS: Based on data from
      the Danish National Patient Registry we identified patients recorded with a first
      time diagnosis of UC or CD in the study periods. Among these - patients were only
      included in the study as incident cases if they had at least one more discharge
      diagnosis of UC/CD or at least three subsequent outpatient visits. RESULTS: We
      identified 17,500 patients with UC and 7863 patients with CD. The mean incidence
      rate for UC in 1995-1998 was 14.4 per 100,000 per year for women and 13.8 for
      men, increasing to 23.2 per 100,000 per year for women and 23.4 for men in the
      period of 2009-2011. The mean incidence rate for CD in 1995-1998 was 7.8 per
      100,000 per year for women and 5.6 for men, increasing to 10.3 per 100,000 per
      year for women and 8.9 for men in the period of 2009-2012. CONCLUSIONS: Based on
      nationwide Danish data from the last two decades, the incidence rates of UC and
      CD have continued to increase.

PMID- 24675474
TI  - In vivo treatment with aflatoxin B1 increases DNA oxidation, base excision repair
      activity and 8-oxoguanine DNA glycosylase 1 levels in mouse lung.
AB  - Carcinogenicity of the mycotoxin aflatoxin B1 (AFB1), which is produced by
      Aspergillus fungi, is associated with bioactivation of AFB1 to AFB1-8,9-exo
      epoxide and formation of DNA adducts. However, AFB1 also causes 8-hydroxy-2'
      deoxyguanosine (8-OHdG) formation in mouse lung DNA, suggesting that oxidative
      DNA damage may also contribute to AFB1 carcinogenicity. The oxidative DNA damage
      5-hydroxy-2'-deoxycytidine (5-OHdC) may also contribute to AFB1 carcinogenicity.
      The objective of the present study was to determine the effect of treatment of
      mice with AFB1 on pulmonary and hepatic: 8-OHdG and 5-OHdC levels; base excision
      repair (BER, which repairs oxidative DNA damage) activities; and on levels of 8
      oxoguanine DNA glycosylase (OGG1, the rate-limiting enzyme in the BER of 8-OHdG).
      Female A/J mice were treated with vehicle (dimethyl sulfoxide) or 50 mg/kg AFB1
      ip. Oxidative DNA damage was measured using HPLC with electrochemical detection,
      BER activity was assessed using an in vitro assay that employs a substrate
      plasmid DNA with 8-OHdG lesions, and OGG1 protein levels were determined by
      immunoblotting. Two hours post treatment, AFB1 increased 8-OHdG levels in mouse
      lung DNA by approximately 69% relative to control (p<0.05), but did not alter 8
      OHdG levels in liver or 5-OHdC levels in lung or liver (p>0.05). AFB1 treatment
      also increased BER activity in mouse lung by approximately 87% (p<0.05) but did
      not affect hepatic BER activity (p>0.05). Levels of OGG1 immunoreactive protein
      were increased in both lung (20%) and liver (60%) (p<0.05). These results are
      consistent with oxidative DNA damage contributing to the carcinogenicity of AFB1
      in this model.

PMID- 24675475
TI  - Phenobarbital and propiconazole toxicogenomic profiles in mice show major
      similarities consistent with the key role that constitutive androstane receptor
      (CAR) activation plays in their mode of action.
AB  - Toxicogenomics (TGx) is employed frequently to investigate underlying molecular
      mechanisms of the compound of interest and, thus, has become an aid to mode of
      action determination. However, the results and interpretation of a TGx dataset
      are influenced by the experimental design and methods of analysis employed. This
      article describes an evaluation and reanalysis, by two independent laboratories,
      of previously published TGx mouse liver microarray data for a triazole fungicide,
      propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB).
      Propiconazole produced an increase incidence of liver tumors in male CD-1 mice
      only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we
      illustrate how experimental design differences between two in vivo studies with
      PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate
      that different researchers using different pathway analysis tools can come to
      different conclusions on specific mechanistic pathways, even when using the same
      datasets. Finally, despite these differences the results across three different
      analyses also show a striking degree of similarity observed for PPZ and PB
      treated livers when the expression data are viewed as major signaling pathways
      and cell processes affected. Additional studies described here show that the
      postulated key event of hepatocellular proliferation was observed in CD-1 mice
      for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR
      nuclear receptor. Thus, with regard to the events which are hallmarks of CAR
      induced effects that are key events in the mode of action (MOA) of mouse liver
      carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a
      similar PB-like CAR-dependent MOA.

PMID- 24675476
TI  - Epigenetic repression of phosphatidylethanolamine N-methyltransferase (PEMT) in
      BRCA1-mutated breast cancer.
AB  - Phosphatidylethanolamine N-methyltransferase (PEMT) plays a critical role in
      breast cancer progression. However, the epigenetic mechanism regulating PEMT
      transcription remains largely unknown. Here, we show that the first promoter
      specific transcript 1 is the major PEMT mRNA species, and methylation of the -132
      site is a key regulatory element for the PEMT gene in BRCA1-mutated breast
      cancer. Mechanistically, hypermethylated -132 site-mediated loss of active
      histone marks H3K9ac and increase of repressive histone marks H3K9me enrichment
      synergistically inhibited PEMT transcription. Clinicopathological data indicated
      that a hypermethylated -132 site was associated with histological grade (P =
      0.031) and estrogen receptor status (P = 0.004); univariate survival and
      multivariate analyses demonstrated that lymph node metastasis was an independent
      and reliable prognostic factor for BRCA1-mutated breast cancer patients. Our
      findings imply that genetic (e.g., BRCA1 mutation) and epigenetic mechanisms
      (e.g., DNA methylation and histone modifications) are jointly involved in the
      malignant progression of PEMT-related breast cancer. 

PMID- 24675477
TI  - Characterization of R-134a superheated droplet detector for neutron detection.
AB  - R-134a (C2H2F4) is a low cost, easily available and chlorine free refrigerant,
      which in its superheated state can be used as an efficient neutron detector. Due
      to its high solubility in water the R-134a based superheated droplet detectors
      (SDD) are usually very unstable unless the detector is fabricated using a
      suitable additive, which stabilizes the detector. The SDD is known to have
      superheated droplets distributed in a short-lived and in a relatively long-lived
      metastable states. We have studied the detector response to neutrons using a
      (241)AmBe neutron source and obtained the temperature variation of the nucleation
      parameters and the interstate kinetics of these droplets using a two-state model.

PMID- 24675479
TI  - Linkage of a national clinical liver transplant database with administrative
      hospital data: methods and validation.
AB  - INTRODUCTION: The UK Liver Transplant Audit (UKLTA) database contains clinical
      information on all liver transplants carried out in the UK. To expand its
      potential for research and service evaluation, we linked it to the Hospital
      Episode Statistics (HES), an administrative database of all admissions to English
      National Health Service (NHS) hospitals. MATERIALS AND METHODS: In the UKLTA
      database, we identified the linkable records of first liver transplantation
      between April 1997 and March 2010. We linked UKLTA records to HES records on the
      basis of NHS number, gender, date of birth, and postcode, as well as procedure
      codes for liver transplantation and dates of transplant. In linked records,
      agreement of primary liver disease diagnoses according to both databases was
      expressed as a proportion of the linked records and using kappa statistic.
      RESULTS: There were 5,815 linkable records in the UKLTA database, of which 4,959
      records were successfully linked with HES (85.3%). Among these, 4,922 records
      (99.3%) had at least one diagnosis coded in HES relevant to an indication for
      liver transplantation. The overall agreement of primary liver disease diagnoses
      between UKLTA data and HES was 77.8% (95% CI 76.6%-79.0%) with a kappa of 0.75
      (0.74-0.76). Diagnostic agreement can be further improved by using broader
      groupings of clinically related diagnoses. CONCLUSION: Linkage of clinical data
      and administrative hospital data provides a rich resource for the study of liver
      transplantation.

PMID- 24675478
TI  - The role of donor-specific antibodies in acute cardiac allograft dysfunction in
      the absence of cellular rejection.
AB  - BACKGROUND: Acute allograft dysfunction (AAD) is an important cause of morbidity
      among heart transplant recipients. The role of donor-specific antibodies (DSAs)
      in AAD, with the increasing use of single antigen bead (SAB) assays that have
      improved the ability to detect DSA, remains unclear. METHODS: We retrospectively
      reviewed 329 heart transplant recipients followed up at our institution. AAD was
      defined as an acute decline in left ventricular ejection fraction to less than
      50% and a decrement of 10% or higher compared to baseline in the absence of
      cellular rejection. Patients with AAD were compared with matched 30 heart
      transplant controls. RESULTS: There were 10 (3%) patients with AAD, 4 (40%) had
      DSA detectable by SAB assay compared to 16 (53%) controls (P=0.43). Peak DSA mean
      fluorescent intensity (MFI) levels were significantly higher at baseline (class I
      and class II) in AAD compared to controls. DSA MFI values increased at the time
      of AAD and returned to baseline values during follow-up for these patients with
      AAD (P<0.05) but remained unchanged over time for controls. Six (60%) patients
      with AAD and 1 (3%) control had antibody-mediated rejection (AMR) by
      endomyocardial biopsy (P<0.01). There were 4 (40%) patients with AAD with no DSA
      or AMR. CONCLUSIONS: AAD after heart transplant is a heterogeneous process
      characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The
      presence of DSA is not associated with AAD, but the quantity assessed by MFI
      levels may play a role.

PMID- 24675482
TI  - Fossil pollen records indicate that Patagonian desertification was not solely a
      consequence of Andean uplift.
AB  - The Patagonian steppe-a massive rain-shadow on the lee side of the southern Andes
      is assumed to have evolved ~15-12 Myr as a consequence of the southern Andean
      uplift. However, fossil evidence supporting this assumption is limited. Here we
      quantitatively estimate climatic conditions and plant richness for the interval
      ~10-6 Myr based on the study and bioclimatic analysis of terrestrially derived
      spore-pollen assemblages preserved in well-constrained Patagonian marine
      deposits. Our analyses indicate a mesothermal climate, with mean temperatures of
      the coldest quarter between 11.4  degrees C and 16.9  degrees C (presently ~3.5 
      degrees C) and annual precipitation rarely below 661 mm (presently ~200 mm).
      Rarefied richness reveals a significantly more diverse flora during the late
      Miocene than today at the same latitude but comparable with that approximately
      2,000 km further northeast at mid-latitudes on the Brazilian coast. We infer that
      the Patagonian desertification was not solely a consequence of the Andean uplift
      as previously insinuated. 

PMID- 24675480
TI  - Interpersonal mentoring and its influence on retention of valued health care
      workers: the moderating role of affective commitment.
AB  - BACKGROUND: Health care organizations (HCOs) invest in knowledge transfer to
      promote improved patient outcomes; however, these investments prove costly when
      health care workers with enhanced knowledge and skills leave to seek better
      employment opportunities. PURPOSE: The aim of this study was to examine the
      impact of interpersonal mentoring on affective organizational commitment and the
      potential moderating effect of affective commitment in the knowledge transfer
      retention relationship. METHODOLOGY/APPROACH: One hundred fifty-three clinicians
      working at a Midwestern acute care hospital and associated clinics were surveyed
      at their worksite. FINDINGS: Clinicians who received more interpersonal mentoring
      were also more likely to have stronger affective commitment. In addition,
      affective commitment moderated the relationship between knowledge transfer and
      turnover intentions, that is, when affective commitment was low, clinicians with
      higher levels of knowledge transfer indicated higher turnover intentions.
      However, clinicians with high levels of affective commitment and knowledge
      transfer reported lower turnover intentions. PRACTICE IMPLICATIONS: HCOs must
      simultaneously invest in knowledge transfer while implementing strategies that
      assist in retaining knowledgeable workers. Interpersonal mentoring appears to
      play an important role in the retention of valued clinicians through its
      influence on affective commitment. HCOs must facilitate cultures that show top
      management support for mentoring through practices such as educational programs,
      flexible scheduling, and reward systems.

PMID- 24675483
TI  - Shortcomings in bladder cancer etiology research and a model for its prevention.
AB  - AIMS AND BACKGROUND: Bladder cancer (BC) is the most expensive cancer to treat.
      Its incidence and mortality have not decreased in the last three decades.
      Numerous uncertainties are still surrounding the etiology of BC. There is a need
      for a low-cost screening test for BC that would be applicable for early detection
      in asymptomatic persons, a test that would preferably be noninvasive and have
      satisfactory sensitivity and specificity. METHODS AND STUDY DESIGN: The first
      part of this paper addresses critical issues in the research into BC etiology,
      which we classified as entrances, toxicity and metabolism, amounts, and duration
      of exposure to carcinogens in the bladder. In the second part, based on the
      proven risk factors for BC, we present a simple scoring system as part of a new
      BC screening method. RESULTS: The heterogeneous results of studies on BC etiology
      are largely due to a lack of research into the compounds (and their mutual
      interactions) present in the urinary bladder, carcinogens absorbed through the
      skin and/or inhaled, and the daily dynamics of exposure to exogenous risk
      factors. We have calculated a score for BC screening which is an integral
      component of a new, four-level system of BC prevention. CONCLUSIONS: Interactions
      of carcinogens and their daily dynamics deserve more attention in further
      clarifying BC etiology. New attempts in BC screening should be focused on urine
      content analyses (carcinogens, antioxidants, vitamins, minerals) and not only on
      hematuria and currently used biomarkers. We propose a score for BC pre-evaluation
      and recruitment for screening and a new model of BC prevention.

PMID- 24675484
TI  - Are antineoplastic drug acute hypersensitive reactions a submerged or an emergent
      problem? Experience of the Medical Day Hospital of the Fondazione IRCCS Istituto
      Nazionale Tumori.
AB  - BACKGROUND: Acute hypersensitivity reactions are adverse events potentially
      associated with antineoplastic drug infusions. Their occurrence can be
      particularly relevant in an outpatient environment where time of administration
      and subsequent observation is limited to a short period of time. In addition,
      concern about the onset of more severe hypersensitivity reactions can limit
      subsequent use of crucial drugs. METHODS: During a 3-year observational period,
      we collected a total of 240 infusional acute hypersensitivity reactions out of
      56,120 administrations performed, with an overall incidence of 0.4%. RESULTS: In
      order of frequency, platinum derivatives, taxanes and monoclonal antibodies
      accounted for the highest incidences. Their relative frequency was: oxaliplatin,
      2.5%; carboplatin, 0.4%; paclitaxel, 1.2%; docetaxel, 1.2%; trastuzumab, 1.2%,
      and rituximab, 1.2%. CONCLUSIONS: Since the number of chemotherapeutic agents is
      steadily increasing, much attention should be paid to such reactions,
      particularly when several administrations are performed daily, and where
      management of the potential risk associated with specific drugs is mandatory.
      Their occurrence represents an unpredictable, unexpected and often hard to manage
      contingency, and our opinion is that observation and consciousness of this issue
      are fundamental for its appropriate management. We describe our experience,
      emphasizing the role of this toxicity and explaining how this awareness allowed
      us to define some empirical rules to handle acute hypersensitivity reactions.

PMID- 24675485
TI  - Analysis of operative morbidity in a single center initial experience with
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Peritoneal carcinomatosis has been traditionally considered a rapidly
      lethal disease and consequently managed by merely palliative options. In the last
      decade, the clinical interest in the condition has increased because encouraging
      results have been reported in association with a new treatment strategy that
      combines cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
      Relatively high rates of severe complications are generally associated to this
      complex procedure. Our aim was to analyze treatment-related morbidity in our
      institutional initial experience. MATERIALS AND METHODS: Since October 2006, 36
      hyperthermic intraperitoneal chemotherapy plus cytoreductive surgery procedures
      have been carried out in our Department. Patients treated showed abdominal
      malignancies and ovarian cancer with peritoneal carcinomatosis. Only 9 patients
      were treated with prophylactic treatment for gastric cancer at high risk to
      develop peritoneal carcinomatosis. RESULTS: In 27 patients, a macroscopically
      complete cytoreduction was done. The overall morbidity was 75%. Grades IV and V
      represented only 11.1%. CONCLUSIONS: Rigorous preoperative workup and strict
      selection criteria allowed a successful safe start of a new program of
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a general
      surgery unit.

PMID- 24675486
TI  - Therapeutic effects and influencing factors in sixty-eight cases of peripheral T
      cell lymphoma unspecified.
AB  - OBJECTIVE: To analyze the clinical characteristics, therapeutic short-term
      efficacy, long-term survival and influencing factors in 68 cases of peripheral T
      cell lymphoma unspecified. METHODS: Sixty-eight cases of peripheral T-cell
      lymphoma unspecified were retrospectively studied. The effect of different
      treatments on survival of patients was analyzed by the Kaplan-Meier method. Using
      single factor analysis and the Cox proportional hazards regression model, the
      effect of the various clinical factors on the survival of patients was evaluated.
      RESULTS: The complete remission rate of 68 cases of peripheral T-cell lymphoma
      unspecified according to treatment was 28%. The 5-year overall survival rate was
      25.63%. Chemotherapy alone and chemotherapy combined with radiotherapy gave
      overall survival rates of 19.4% and 37.1%, respectively. Chemotherapy combined
      with radiotherapy gave a long-term survival rate significantly superior to that
      of chemotherapy alone (P <0.05). CONCLUSIONS: Patients with peripheral T-cell
      lymphoma unspecified treated by the CHOP chemotherapy regimen had a high response
      rate but a low long-term survival rate. A complete remission with initial
      treatment and chemotherapy combined with radiotherapy can improve patient
      survival. The performance score before treatment, therapeutic effect, and bone
      marrow involvement are independent factors that affect survival.

PMID- 24675487
TI  - Clinical features and treatment outcomes of skin cancer arising from burn scar: a
      single-institution experience.
AB  - AIMS AND BACKGROUND: This study was conducted to investigate the
      clinicopathological features and long-term outcomes of patients with skin cancer
      arising from burn scar (SCBS). PATIENTS AND METHODS: We retrospectively reviewed
      the medical records of patients diagnosed with SCBS between January 2000 and May
      2012. A total of 44 patients were enrolled in this study. RESULTS: The median
      latent period between burn injury and development of SCBS was 32 years (range, 8
      78 years). The most frequent sites of SCBS were the lower limbs (68.2%) followed
      by the upper limbs (15.9%) and trunk (11.4%). Most patients (95.4%) had squamous
      cell carcinoma. Of 34 patients with localized disease at the time of diagnosis,
      33 patients are alive with no evidence of recurrence. Of 10 patients with
      regional lymph node metastasis (referred to as locally advanced disease), 4 died
      of disease progression and 5 are alive with metastatic disease in the lymph
      nodes, bone or lung. Patients with localized disease survived longer than
      patients with locally advanced disease ( P = 0.000). In patients with locally
      advanced disease, the median overall survival time was 16 months (95% CI, 2.88
      29.4 months). CONCLUSIONS: While localized SCBS is a potentially curable disease,
      locally advanced SCBS has a poor prognosis in spite of aggressive treatment.
      These results suggest that early recognition and aggressive treatment are
      essential to improve the outcomes of SCBS.

PMID- 24675488
TI  - Changes in patterns of practice for prostate cancer radiotherapy in Italy 1995
      2003. A survey of the Prostate Cancer Study Group of the Italian Radiation
      Oncology Society.
AB  - AIMS AND BACKGROUND: In 2002, a survey including 1759 patients treated from 1980
      to 1998 established a "benchmark" Italian data source for prostate cancer
      radiotherapy. This report updates the previous one. METHODS: Data on clinical
      management and outcomes of 3001 patients treated in 15 centers from 1999 through
      2003 were analyzed and compared with those of the previous survey. RESULTS:
      Significant differences in clinical management (-10% had abdominal magnetic
      resonance imaging; +26% received >=70 Gy, +48% conformal radiotherapy, -20%
      pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial
      5-year overall, disease-specific, clinical relapse-free, and biochemical relapse
      free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate
      analysis, D'Amico risk categories significantly impacted on all the outcomes;
      higher radiotherapy doses were significantly related with better overall survival
      rates, and a similar trend was evident for disease-specific and biochemical
      relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was
      24.8% and was significantly related to higher radiotherapy doses (P <0.001).
      CONCLUSIONS: The changing patterns of practice described seem related to an
      improvement in efficacy and safety of radiotherapy for prostate cancer. However,
      the impact of the new radiotherapy techniques should be prospectively evaluated.

PMID- 24675489
TI  - Breast cancer bone metastases: an epidemiologic study in selected radiation
      departments.
AB  - AIMS: To quantify radiation treatments for bone metastases from breast cancer in
      three Sicilian provinces (Messina, Catania, Ragusa) with respect to the general
      population and the incidence and prevalence of breast cancer in this macro-area
      in a 8-year period. METHODS: All bone metastasis patients treated using
      radiotherapy in 8 radiation departments operating in the provinces of Messina,
      Catania and Ragusa were collected. Among these, metastases from breast carcinoma
      were analyzed according to year of irradiation. An analysis of breast cancer
      incidence and prevalence with respect to inhabitants in this macro-area was
      conducted using literature and census data. RESULTS: From January 2004 to
      December 2011, irradiation was delivered in 4419 bone metastasis patients. Among
      these, 1617 had a primary breast cancer with a median treatment per year of 206.5
      (range, 164-251); 211 patients were treated in 2004 and 206 in 2011. In 2004,
      there were 1,048,957 female residents in the three provinces and 1,065,422 in
      2011. The reported breast cancer incidence and prevalence in Sicily was
      respectively 100.79/100,000 and 908.54/100,000 in 2004 and 108.41/100,000 and
      1091.29/100,000 in 2010. CONCLUSIONS: There has been an increase in both
      incidence and prevalence of breast cancer in Sicily. Nevertheless, it seems that
      there was no increment in skeletal-related events requiring irradiation in such
      patients in eastern Sicily radiation departments.

PMID- 24675490
TI  - Helical image-guided stereotactic body radiotherapy (SBRT) for the treatment of
      early-stage lung cancer: a single-institution experience at the Willis-Knighton
      Cancer Center.
AB  - AIMS AND BACKGROUND: Our aim is to report on the clinical methods and outcomes of
      helical intensity-modulated stereotactic body radiotherapy (SBRT) for the
      treatment of early-stage non-small cell lung cancer (NSCLC). METHODS AND STUDY
      DESIGN: Seventy-nine patients with stage I NSCLC underwent helical SBRT with 48
      Gy in 4 fractions or 60 Gy in 5 fractions. All patients underwent 18F
      fluorodeoxyglucose (FDG) positron emission tomography (PET) or FDG-PET/computed
      tomography (CT) scanning in the immobilized treatment position for planned fusion
      with a separate kilovoltage (KV) CT simulation prior to treatment. Megavoltage CT
      images were obtained on the treatment unit prior to therapy and repeated at mid
      fraction with comparison and fusion to the KV CT simulation planning images to
      assure setup accuracy. Serial follow-up with FDG-PET or FDG-PET/CT was performed
      at 3-4 months and every 6 months thereafter. RESULTS: Median follow-up was 27
      months (range, 4-82 months). Overall local control rate (LCR) was 93.6% (95%
      confidence interval [CI], 86.0-97.3%) and 3-year overall survival (OS) was 58.4%
      (95% CI, 47.2-69.5%). For patients with T1N0M0 disease (n = 59) the LCR was 94.9%
      (95% CI, 86.1-98.3%) and the 3-year OS was 62.8% (95% CI, 49.9-73.9%). Patients
      treated with 60 Gy had longer 3-year OS than patients treated with 48 Gy (65.2%
      vs 37.5%; P = 0.044). SBRT-related toxicity was modest, with 10 patients
      developing grade 1/2 chest wall toxicity based on the Common Terminology Criteria
      for Adverse Events (CTCAE). CONCLUSION: Image-guided SBRT with helical IMRT
      delivered in 4 or 5 fractions of 12 Gy with rigid immobilization, FDG-PET
      assisted targeting, and repeat mid-fraction CT scan is an effective treatment for
      early NSCLC.

PMID- 24675491
TI  - Comparing radiotherapy with or without intracavitary hyperthermia in the
      treatment of primary nasopharyngeal carcinoma: a retrospective analysis.
AB  - AIMS AND BACKGROUND: A retrospective study was performed to evaluate the
      contribution of intracavitary hyperthermia in patients with nasopharyngeal
      carcinoma who received radiation therapy. METHODS AND STUDY DESIGN: Patients with
      nasopharyngeal carcinoma were treated with radiotherapy alone or with
      radiotherapy plus hyperthermia of the primary tumor. All patients were treated in
      a uniform fashion by definitive-intent radiotherapy in both groups. In the
      radiotherapy plus hyperthermia group, patients were treated with microwave
      heating hyperthermia delivered twice a week in combination with radiation.
      RESULTS: Between November 1992 to September 1994, 225 patients were recruited,
      with 98 patients matched to the criteria of either treatment group (49 in the
      radiotherapy and 49 in the radiotherapy plus hyperthermia group). Ninety-eight
      patients were included in the treatment response and 87 patients in the survival
      analysis according to the intent-to-treat principle (11 patients were lost to
      follow-up). Overall survival did not show a significant difference between the
      two groups (81 vs 86 months of median survival time, respectively, P = 0.068).
      However, there were significant differences not only in progression-free survival
      (median months, 60 vs 100, respectively, P = 0.036), but also in local
      progression-free survival (median months, 54 vs 111, respectively, P = 0.029)
      between the radiotherapy and radiotherapy plus hyperthermia groups. No
      statistical difference was noted in the cumulative incidence of grade 3 adverse
      events or late radiation morbidity during follow-up between the two study groups.
      CONCLUSIONS: The retrospective study showed that hyperthermia combined with
      radiation therapy can improve progression-free survival and local progression
      free survival, although no increase in overall survival was observed. Thus, the
      inclusion of hyperthermia in the treatment of nasopharyngeal carcinoma using
      radiation offers no survival benefit but may help to improve the current standard
      of care consisting of radiation and chemotherapy.

PMID- 24675492
TI  - Prognostic factors affecting survival in malignant pleural mesothelioma: analysis
      of 125 subjects.
AB  - AIM OF THE STUDY: Determining the pre-treatment prognostic factors in malignant
      pleural mesothelioma is important in terms of estimating the course of the
      disease and selecting patients who are candidate for multimodal therapy. The aim
      of the study was to determine the prognostic factors affecting survival in
      patients with malignant pleural mesothelioma. STUDY DESIGN: One hundred and
      twenty-five patients who had been diagnosed histologically as having malignant
      pleural mesothelioma over the past 5 years were evaluated retrospectively.
      Relationships of survival of the patients with their age, gender, exposure to
      asbestos, smoking history, platelet, hemoglobin, leukocyte (WBC) and serum LDH
      values, histology, performance score and stage of disease were examined. RESULTS:
      Advanced clinical stage, N2 nodal involvement and the presence of distant
      metastasis were found to be related to survival. Sarcomatous histology was found
      to be a poor prognostic factor independently of other factors. CONCLUSIONS: We
      showed that histological subtype and stage of disease were the most important
      parameters in planning the treatment, especially in determining the patients who
      were candidate for multimodal treatment and in estimating the prognosis.

PMID- 24675493
TI  - Clinical significance of immunohistochemical expression of cancer/testis tumor
      associated antigens (MAGE-A1, MAGE-A3/4, NY-ESO-1) in patients with non-small
      cell lung cancer.
AB  - AIMS AND BACKGROUND: This paper deals with the clinical significance of the
      immunohistochemical expression of MAGE-A1, MAGE-A3/4 and NY-ESO-1 antigens in
      patients with non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: The
      study included 80 patients with NSCLC (40 with adenocarcinoma, 40 with squamous
      cell carcinoma) who had undergone surgery. MAGE-A1 and MAGE-A3/4 antigen
      expression was determined by an immunohistochemical method using the monoclonal
      antibody 57B, and NY-ESO-1 antigen expression was determined with the addition of
      the B9.8.1.1 antibody. The expression of these antigens was compared with the
      clinicopathological features of the tumors and the survival of the patients.
      RESULTS: MAGE-A1, MAGE-A3/4 and NY-ESO-1 were expressed in 17.3%, 44.4% and 18.5%
      of NSCLC patients, respectively. A statistically higher immunohistological
      expression rate of MAGE-A3/4 was found in squamous cell carcinoma (P <0.001) and
      a significantly higher amount of tumor necrosis was observed in tumors with MAGE
      3 expression (P = 0.001), but no correlation with positive lymph nodes was found.
      There was a statistically significant correlation between MAGE-A1 expression in
      adenocarcinoma and the presence of tumor necrosis (P = 0.05). Furthermore, there
      was a significant correlation between NY-ESO-1 expression and positive lymph
      nodes in adenocarcinoma, but not in squamous cell carcinoma. No statistically
      significant difference in patient survival was found with regard to tumor type
      and the observed histopathological characteristics except tumor size.
      Statistically significantly better survival was found in the group of patients
      with adenocarcinomas who had positive expression of MAGE-A3/4 (P = 0.012).
      CONCLUSIONS: This study demonstrated that the expression of MAGE-A3/4 antigen
      might be a valuable prognostic factor regarding survival in patients with NSCLC.

PMID- 24675494
TI  - Prognostic factors in older patients with advanced non-small cell lung cancer in
      China.
AB  - AIMS AND BACKGROUND: The human life expectancy and the incidence of lung cancer
      have increased dramatically in recent years. As a result, there is a high demand
      for the management of older patients with advanced non-small cell lung cancer
      (NSCLC) in clinical practice. The purpose of this study is to evaluate the
      prognostic factors in >=65-year-old patients with advanced NSCLC in China.
      METHOD: This study involved a retrospective review of 78 >=65-year-old patients
      with a diagnosis of NSCLC and at an advanced stage of disease, defined as stage
      IIIB or IV. All patients were followed up for a 3-year interval to determine the
      survival rates. Clinical data including gender, smoking history, comorbidities,
      performance status (PS), histological differentiation, disease stage, treatment
      and overall survival were recorded. The log-rank test was used to calculate
      survival rates. Multivariate Cox regression analysis was performed to determine
      independent prognostic factors. RESULTS: The 1-year, 2-year and 3-year survival
      rates of the 78 patients were 44.9%, 23.1% and 9.0%, respectively. In univariate
      analysis by the log-rank test, the 3-year survival rate was significantly
      associated with PS (P <0.01), disease stage (P <0.01) and chemotherapy treatment
      (P <0.01). The results of multivariate Cox regression analysis confirmed that PS
      and disease stage were independent prognostic factors. CONCLUSION: The 3-year
      survival rate in >=65-year-old patients with advanced NSCLC was significantly
      associated with PS, disease stage and chemotherapy. PS and disease stage were
      independent prognostic factors. Older patients with advanced NSCLC in China might
      benefit from chemotherapy.

PMID- 24675495
TI  - Clinico-pathological study of K-ras mutations in colorectal tumors in Saudi
      Arabia.
AB  - AIMS AND BACKGROUND: K-ras gene mutations contribute to the pathogenesis of
      colorectal cancer. We characterized K-ras mutations in colorectal tumors in
      patients in the Kingdom of Saudi Arabia, in terms of geographic area, age,
      gender, histology, stage, and anatomical localization. METHODS: Medical records
      and paraffin-embedded tumor samples from 150 consecutive patients with
      histologically proven colorectal adenocarcinoma referred to two centers in Saudi
      Arabia were analyzed using an LCD-array kit. RESULTS: K-ras mutations occurred in
      56% of the patients; 48.7% of the mutations were in codon 12, most commonly
      p.G12V and p.G12D (each 35.6% of codon 12 mutations). Codon 13 mutations occurred
      in 7.3% of tumors: of these, most were p.G13D (90.9%) with the remainder p.G13R
      (9.1%). Codon 12 mutations overall were associated significantly with stage IVb
      tumors (P = 0.022) and rectal tumors (P = 0.028), with a trend of an association
      with a sigmoid location (P = 0.054). The p.G12V mutation was significantly
      associated with sigmoid tumors (P = 0.021) and negatively associated with left
      sided tumors (P = 0.011), with a trend of an association with age >=70 years (P =
      0.062) and rectal tumors (P = 0.063). Other clinicopathological features were not
      significantly associated with K-ras mutations. CONCLUSIONS: K-ras mutations are
      common among the Saudi colorectal cancer population, especially pG12V and pG12D
      in codon 12, and are more frequent in sigmoid and rectal adenocarcinomas and
      stage IVB tumors.

PMID- 24675497
TI  - Assessment of impact of late postoperative physical functional disabilities on
      quality of life in breast cancer survivors.
AB  - AIMS AND BACKGROUND: Breast cancer is the second most common malignancy among
      women. Surgical and supplemental (or adjuvant) therapies to combat the disease
      may implicate physical functional consequences for the ipsilateral upper
      extremity. These dysfunctions may persist for many years and have repercussions
      on the performance of daily living activities. The aim of this study was to
      assess the impact of physical functional disabilities on quality of life in women
      after breast cancer surgery. METHODS AND STUDY DESIGN: Eighty-two women in the
      postoperative period of conservative surgery for breast cancer participated in
      the study. Axillary lymph node dissection was performed in all patients and mean
      time since surgery was 5.78 (+/- 4.60) years. The women responded to a
      questionnaire to assess quality of life (FACT-B) and to another to assess
      functional capacity (QuickDASH). They were then referred to physical therapy
      examination to measure shoulder range of motion (flexion, abduction and external
      rotation) and arm volume. RESULTS: Range of motion in the ipsilateral shoulder
      was limited: shoulder flexion range of motion reached a mean value of 155.44o (+/
      28.31), mean abduction was 149.05o (+/- 29.51), and mean external shoulder
      rotation was 58.44o (+/- 29.17). These limitations had a negative impact on
      functional capacity and global quality of life. Lymphedema was present in 28.04%
      of women assessed and did not impair quality of life or functional capacity.
      CONCLUSION: Physical functional disabilities were present in the late
      postoperative period of breast cancer survivors and limited shoulder range of
      motion negatively influenced their functional capacity and quality of life. The
      presence of lymphedema did not impair functional capacity or quality of life in
      the postoperative period.

PMID- 24675496
TI  - Topoisomerase II alpha and microtubule-associated protein-tau as a predictive
      marker in axillary lymph node positive breast cancer.
AB  - AIMS AND BACKGROUND: The aims of this study were to investigate the correlation
      between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP
      tau) and other prognostic factors in breast cancer and to evaluate the predictive
      value of TOP2A and MAP-tau in breast cancer patients who received anthracycline
      and taxane-containing adjuvant chemotherapy. METHODS AND STUDY DESIGN: Seventy
      patients with axillary lymph node positive breast cancer who underwent curative
      surgery between January 2000 and December 2005 were evaluated retrospectively.
      The levels of protein expression of TOP2A and MAP-tau were assessed using
      immunohistochemistry. RESULTS: Among the 70 patients, 43 (61.4%) showed TOP2A
      overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was
      associated with p53 positivity and high histological grade. MAP-tau positivity
      was associated with a lower positive lymph node ratio, lower proliferative
      activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau
      expression, there was no significant difference in disease-free survival in the
      breast cancer patients who received anthracycline and taxane-containing adjuvant
      chemotherapy. CONCLUSIONS: We conclude that immunohistochemical analysis of TOP2A
      and MAP-tau protein expression may not predict the benefits of adjuvant
      anthracycline and taxane chemotherapy in axillary node positive breast cancer.

PMID- 24675498
TI  - Role of multidimensional assessment of frailty in predicting short-term outcomes
      in hospitalized cancer patients: results of a prospective cohort study.
AB  - AIMS AND BACKGROUND: The study analyzed the value of physical and psychosocial
      frailty assessment in predicting the need for supportive care and the risk of
      short-term failures after discharge in hospitalized cancer patients. METHODS AND
      STUDY DESIGN: Frailty was assessed in 350 consecutive patients using a
      multidimensional tool. Patients were followed for 4 months after discharge to
      record the occurrence of chemotherapy interruption, urgent hospital readmission
      or death. The association between patient characteristics and the outcomes were
      analyzed with either logistic or Cox multivariable models. RESULTS: About 40% of
      patients were classified as frail, with a higher prevalence of clinical frailty
      (alone or together with psychosocial frailty). Psychosocial frailty was
      positively associated with the need for supportive care at discharge (adjusted
      OR, 3.46; 95% CI, 1.55-7.76) but did not predict a worse prognosis when other
      important clinical factors were considered. However, the need for supportive care
      at discharge, in addition to advanced disease and reduced performance status, was
      a strong predictor of short-term hospital readmission or death (HR 7.50; 95% CI,
      3.12-18.02). CONCLUSIONS: A more comprehensive assessment of frailty in cancer
      patients can aid in the timely identification of the need for supportive care
      after hospital discharge and improves the prediction of the short-term risk of
      hospital readmission or death.

PMID- 24675499
TI  - The inhibition of Wnt/beta-catenin signaling pathway in human colon cancer cells
      by sulindac.
AB  - The aberrant activation of Wnt/beta-catenin signaling plays important roles in
      the initial development of colon cancer. Sulindac is a commonly used non
      steroidal anti-inflammatory drug. We demonstrated the effects of sulindac on
      growth inhibition, apoptosis induction, and Wnt/beta-catenin signaling
      suppression in human colon cancer cells. Sulindac significantly inhibited
      proliferation of HT-29 colon cancer cells in a dose- and time-dependent manner.
      Sulindac was found to induce the apoptosis of HT-29 cells and inhibit the
      Wnt/beta-catenin pathway. The inhibition was further confirmed by the decreased
      protein levels of beta-catenin. The results indicate that sulindac may play a
      beneficial role in the comprehensive treatment of colon cancer. 

PMID- 24675500
TI  - Mechanisms underlying regulation of cell cycle and apoptosis by hnRNP B1 in human
      lung adenocarcinoma A549 cells.
AB  - AIMS AND BACKGROUND: Overexpression of heterogeneous nuclear ribonucleoprotein B1
      (hnRNP B1), a nuclear RNA binding protein, has been reported to occur in early
      stage lung cancer and in premalignant lesions. DNA-dependent protein kinase (DNA
      PK) is known to be involved in the repair of double-strand DNA breaks. Reduced
      capacity to repair DNA has been associated with the risk of lung cancer. METHODS
      AND STUDY DESIGN: We investigated a link between hnRNP B1 and DNA-PK and their
      effects on proliferation, cell cycle, and apoptosis in the human lung
      adenocarcinoma cell line A549. RESULTS: We found that hnRNP B1 and DNA-PK
      interact with each other in a complex fashion. Reducing hnRNP B1 expression in
      A549 cells with the use of RNAi led to upregulation of p53 activity through
      upregulation of DNA-PK activity but without inducing p53 expression. Further,
      suppression of hnRNP B1 in A549 cells slowed cell proliferation, promoted
      apoptosis, and induced cell cycle arrest at the G1 stage. The presence of NU7026
      reduced the arrest of cells at the G1 stage and reduced the apoptosis rate while
      promoting cell growth. CONCLUSION: Taken together, our results demonstrate that
      by regulating DNA-PK activity, hnRNP B1 can affect p53-mediated cell cycle
      progression and apoptosis, resulting in greater cell survival and subsequent
      proliferation.

PMID- 24675501
TI  - Penile metastasis from prostate cancer: a case report.
AB  - Metastatic involvement of the penis is rare. About 80% of secondary lesions
      originate from pelvic primary tumors, mainly bladder and prostate. We present a
      case of prostatic mucinous adenocarcinoma with penile metastasis symptomatic for
      pain, which was treated with external-beam radiation (35 Gy/14 fractions; 2.5 Gy
      daily) combined with androgen deprivation, resulting in complete pain relief and
      objective response after treatment. 

PMID- 24675502
TI  - Acute immune hematological complication of oxaliplatin. A series of 3 cases.
AB  - We report a series of three cases of oxaliplatin-related hematological immune
      reactions. Two patients developed acute immune hemolytic anemia and the third
      patient had severe thrombocytopenia. One patient had minor undiagnosed hemolysis
      after the previous chemotherapy cycle and two of our three patients had minor
      allergic signs just before the hemolysis. Fifteen cases of immune hemolytic
      anemia have been reported in the literature, of which only the first was fatal.
      One case of hemolytic uremic syndrome has been described. Anemia in cancer
      patients is not always related to myelosuppression and hemolytic anemia can be a
      severe side effect of oxaliplatin administration. 

PMID- 24675504
TI  - Management of cancer cachexia (reply).

PMID- 24675503
TI  - Management of cancer cachexia.

PMID- 24675505
TI  - Overcoming T790M-driven acquired resistance to EGFR-TKIs in NSCLC with afatinib:
      a case report.
AB  - The identification of activating EGFR gene mutations and the availability of
      effective target therapies such as gefitinib and erlotinib have radically changed
      the therapeutic approach and prognosis for patients with advanced EGFR-mutated
      non-small cell lung cancer (NSCLC). However, despite an initial response to EGFR
      tyrosine kinase inhibitors (TKIs), acquired resistance inevitably develops and
      the way to overcome it is an open challenge. We report the first case, to our
      knowledge, of a patient affected by metastatic EGFR-mutated NSCLC with T790M
      driven acquired TKI resistance who obtained a significant response to afatinib.
      Considering the improvement achieved in all disease sites but those in the brain,
      this case puts a strain on afatinib's activity on brain metastases. 

PMID- 24675506
TI  - Comparison between particulate matter and ultrafine particle emission by
      electronic and normal cigarettes in real-life conditions.
AB  - AIMS: Electronic cigarettes may be safer than conventional cigarettes as they
      generate less indoor pollution in terms of particulate matter (PM); however,
      recent findings in experimental conditions demonstrated that secondhand exposure
      to PM may be expected from e-cigarette smoking. The aim of the present study was
      to investigate the emission of PM generated by e-cigarettes and normal cigarettes
      under real-life conditions. METHODS: Real-time measurement and comparison of PM
      and ultrafine particles (UFP) generated by electronic cigarettes with and without
      nicotine and by normal cigarettes in a 50 m3 office of an Italian comprehensive
      cancer center was performed. PM mass as PM1, PM2.5, PM7, PM10, total suspended
      particles (TSP) in MUg/m3 and UFP in number of particles per cubic centimeter
      from 10 to 1,000 nanometers were measured. Outdoor concentrations were measured
      contemporaneously to compensate for urban background changes. RESULTS: Regardless
      of their nicotine content, e-cigarettes generated lower PM levels than
      conventional cigarettes. Notably, nicotine-enriched e-cigarettes produced lower
      PM levels than their nicotine-free counterparts. CONCLUSION: E-cigarettes appear
      to generate less indoor pollution than normal cigarettes and may therefore be
      safer. Further studies are required to investigate the long-term health-related
      effects of secondhand e-cigarette exposure.

PMID- 24675507
TI  - Rationale and protocol of RESORT, a randomized, open-label, multicenter phase II
      study to evaluate the efficacy of sorafenib in patients with advanced renal cell
      carcinoma after radical resection of the metastases.
AB  - The introduction of targeted agents did not totally resolve the approach to the
      treatment of metastatic renal cell carcinoma (mRCC) because complete response is
      rarely achieved. Recent findings seem to indicate that metastasectomy may improve
      survival. The RESORT study was designed to evaluate the additional clinical
      benefit of metastasectomy followed by sorafenib in a population of mRCC patients.
      With the aim of evaluating time to recurrence, 132 patients with mRCC who
      underwent radical resection of metastases at the time of recurrence after
      nephrectomy will be randomized to receive either sorafenib or best supportive
      care. Targeted treatment will be administered for up to 52 weeks or discontinued
      in the case of disease recurrence or unacceptable toxicity. Patients will be
      followed for a period of 36 months. 

PMID- 24675508
TI  - Everolimus in advanced solid tumors: when to start, early or late?
AB  - Everolimus is an oral derivative of rapamycin which acts as a signal transduction
      inhibitor. It targets the mammalian target of rapamycin (mTOR), a key
      serine/threonine kinase regulating cell growth and angiogenesis. Everolimus has
      been approved for the treatment of pancreatic neuroendocrine tumors (pNETs),
      metastatic renal cell carcinoma (mRCC), and breast carcinoma. The activity of
      everolimus was demonstrated in three phase III randomized placebo-controlled
      trials, RADIANT-3, RECORD 1 and BOLERO 2, in patients with pNETs, mRCC and breast
      carcinoma, respectively. All three trials reported a statistically significant
      increase in median progression-free survival, the primary endpoint of the
      studies, in favor of everolimus. The absence of an overall survival benefit could
      be related to the cross-over design and subsequent therapies. The focus of our
      paper is on the best timing to start treatment with everolimus, while additional
      questions concern the opportuneness of intermittent use of everolimus
      specifically in long-responding patients. Lastly, we suggest this treatment could
      be optimized on the basis of patient and disease characteristics. 

PMID- 24675509
TI  - Identification of microRNA expression patterns in cutaneous and uveal melanoma
      cell lines.
AB  - AIMS AND BACKGROUND: microRNA (miRNA)-mediated epigenetic regulation of tumor
      suppressor genes and oncogenes has been shown to play a central role in
      melanomagenesis. Here, we focused on the identification of miRNA signatures in
      the cutaneous melanoma cell line G361 and the uveal melanoma cell line OCM-1.
      METHODS AND STUDY DESIGN: We carried out genome-wide miRNA expression profiling
      using a human miRNA microarray platform (Agilent Sanger miRBase, release 10.1) in
      both cell lines. RESULTS: Our screening revealed significant alteration of miRNA
      expression profiles in melanoma cell lines compared with normal human epidermal
      melanocytes. We defined 208 differentially expressed miRNAs in OCM-1 and 112 in
      G361. By comparison analysis between the resulting miRNA expression profiles, we
      identified 96 miRNAs that were modified in both cell models. Among these commonly
      modified miRNAs, 65 were downregulated, 28 upregulated, and 3 exhibited a
      different expression trend. CONCLUSIONS: Although preliminary, our analysis
      identified new melanoma-associated miRNAs providing novel miRNA candidates for
      the development of anticancer target therapy.

PMID- 24675510
TI  - Brain and multiorgan metastases from uterine leiomyosarcoma.
AB  - A 59-year-old woman, diagnosed 7 years ago with uterine leiomyosarcoma (ULMS),
      developed several intrathoracic, pelvic and lately intra-abdominal and brain
      metastases. On each occasion, surgical resection was followed by a course of
      failed chemotherapy. Lately she presented with acute neurological deterioration
      and focal signs. Magnetic resonance imaging demonstrated two presumed brain
      parenchymal lesions involving the supratentorial and infratentorial compartments.
      She underwent surgical resection of the left cerebellar lesion. Histological
      analysis of the brain specimen confirmed the presence of metastatic ULMS.
      Leiomyosarcoma of the uterus is an uncommon tumor with a very aggressive course
      and poor prognosis. Multiple organ metastases from ULMS are an extremely rare
      condition, and prognostically alarming despite current treatments. 

PMID- 24675511
TI  - Within-host bacterial diversity hinders accurate reconstruction of transmission
      networks from genomic distance data.
AB  - The prospect of using whole genome sequence data to investigate bacterial disease
      outbreaks has been keenly anticipated in many quarters, and the large-scale
      collection and sequencing of isolates from cases is becoming increasingly
      feasible. While sequence data can provide many important insights into disease
      spread and pathogen adaptation, it remains unclear how successfully they may be
      used to estimate individual routes of transmission. Several studies have
      attempted to reconstruct transmission routes using genomic data; however, these
      have typically relied upon restrictive assumptions, such as a shared topology of
      the phylogenetic tree and a lack of within-host diversity. In this study, we
      investigated the potential for bacterial genomic data to inform transmission
      network reconstruction. We used simulation models to investigate the origins,
      persistence and onward transmission of genetic diversity, and examined the impact
      of such diversity on our estimation of the epidemiological relationship between
      carriers. We used a flexible distance-based metric to provide a weighted
      transmission network, and used receiver-operating characteristic (ROC) curves and
      network entropy to assess the accuracy and uncertainty of the inferred structure.
      Our results suggest that sequencing a single isolate from each case is inadequate
      in the presence of within-host diversity, and is likely to result in misleading
      interpretations of transmission dynamics--under many plausible conditions, this
      may be little better than selecting transmission links at random. Sampling more
      frequently improves accuracy, but much uncertainty remains, even if all genotypes
      are observed. While it is possible to discriminate between clusters of carriers,
      individual transmission routes cannot be resolved by sequence data alone. Our
      study demonstrates that bacterial genomic distance data alone provide only
      limited information on person-to-person transmission dynamics.

PMID- 24675512
TI  - Expression of Smac induced by the Egr1 promoter enhances the radiosensitivity of
      breast cancer cells.
AB  - Breast cancer is one of the most prevalent cancers worldwide. Moreover, despite
      advances in antineoplastic therapies, induction of tumor cell death without off
      target cytotoxicity remains a challenge. However, recent developments in
      localized radiotherapy and gene therapy have provided an opportunity to explore
      the potential for these strategies to be additive for the induction of cell death
      in tumor cells. Here, a novel adenoviral shuttle vector containing the
      proapoptotic gene Smac under the control of the ionizing radiation (IR)-induced
      Egr1 promoter was constructed. Following the transient transfection of the
      construct into MCF-7 and MDA-MB-435 breast cancer cell lines, acute and abundant
      expression of Smac was observed in response to IR treatment. Further analysis
      confirmed that the induction of Smac expression resulted in a decrease in cell
      viability, a slower rate of cell growth, a higher level of apoptosis and altered
      cell cycle progression. Using a clonogenic assay, IR-induced Smac expression was
      also found to significantly sensitize Smac-expressing cells to radiation-induced
      cell death. Taken together, these data suggest that Smac expression driven by the
      Egr1 promoter has the potential to serve as a radiotherapy-dependent gene therapy
      agent.

PMID- 24675514
TI  - Towards understanding elastocapillarity: comparing wetting of soft and rigid
      plates.
AB  - Elastocapillarity plays a significant role in the buoyancy and water repellency
      of soft objects floating on water. In this paper, we analyze the wetting behavior
      of an elastic and circular plate pressing a liquid surface. The geometry and
      stability of axisymmetric infinite liquid menisci are investigated, and their
      qualitative difference from two-dimensional planar menisci is revealed. By
      comparing the wetting processes of rigid and elastic circular plates under
      pressing, we show that flexibility benefits both the maximal depth and buoyancy a
      plate can reach. The results are helpful not only for understanding the living
      behavior of some aquatic creatures but also for the design of biomimetic soft
      microrobotics. 

PMID- 24675513
TI  - Unambiguous observation of shape effects on cellular fate of nanoparticles.
AB  - Cellular fate of nanoparticles is vital to application of nanoparticles to cell
      imaging, bio-sensing, drug delivery, suppression of drug resistance, gene
      delivery, and cytotoxicity analysis. However, the current studies on cellular
      fate of nanoparticles have been controversial due to complications of interplay
      between many possible factors. By well-controlled experiments, we demonstrated
      unambiguously that the morphology of nanoparticles independently determined their
      cellular fate. We found that nanoparticles with sharp shapes, regardless of their
      surface chemistry, size, or composition, could pierce the membranes of endosomes
      that carried them into the cells and escape to the cytoplasm, which in turn
      significantly reduced the cellular excretion rate of the nanoparticles. Such
      features of sharp-shaped nanoparticles are essential for drug delivery, gene
      delivery, subcellular targeting, and long-term tracking. This work opens up a
      controllable, purely geometrical and hence safe, degree of freedom for
      manipulating nanoparticle-cell interaction, with numerous applications in
      medicine, bio-imaging, and bio-sensing. 

PMID- 24675515
TI  - Radial glial cell: critical functions and new perspective as a steroid synthetic
      cell.
AB  - The radial glial cell (RGC) is a glial cell type in the central nervous system of
      all vertebrates. Adult teleost fish have abundant RGCs in the brain in contrast
      to mammals. Adult fish RGCs have many important functions, including forming a
      structural scaffold to guide neuronal migration and serving as the progenitor
      cells in the brain to generate neurons. The role of the RGC in adult neurogenesis
      explains the high regenerative capacity of adult fish brain. There is increasing
      evidence from several species that some glial cells produce or metabolize
      steroids. It is now well-known that teleost RGCs express aromatase and produce
      estrogens from androgen precursors, which may be important for local
      neuroendocrine functions and regulation of neurogenesis. The question of whether
      RGCs are capable of de novo steroid synthesis from cholesterol remains
      unanswered. However, the expression of steroidogenic acute regulatory protein,
      and the key enzyme cytochrome P450 17alpha-hydroxylase in primary cultures of
      goldfish RGCs indicate the potential to produce 17alpha-hydroxy-pregnenolone and
      thus other steroid intermediates. The possibility of synthesizing additional non
      estrogenic steroids may indicate new functions for the RGC. 

PMID- 24675516
TI  - Converging on neurodegenerative mechanisms.

PMID- 24675517
TI  - Global optimization of somatic variant identification in cancer genomes with a
      global community challenge.

PMID- 24675518
TI  - RHOA mutations in peripheral T cell lymphoma.
AB  - Peripheral T cell lymphomas are rare but aggressive non-Hodgkin lymphomas derived
      from mature T lymphocytes or natural killer (NK) cells. New studies identify
      recurrent dominant-negative mutation of the RHOA GTPase gene in these lymphomas. 

PMID- 24675519
TI  - Ancient human oral plaque preserves a wealth of biological data.
AB  - A new study explores the ancient oral microbiome from the well-preserved dental
      calculus samples of four human individuals who lived during medieval times, using
      a suite of genomic, proteomic and microscopic approaches. The authors investigate
      the evolution of dental pathogens by reconstructing the genome of the periodontal
      pathogen Tannerella forsythia and also identify antibiotic resistance genes,
      bacterial virulence factors and host immune defense proteins. 

PMID- 24675520
TI  - Zinc transport and diabetes risk.
AB  - Genome-wide association studies have previously identified variants in SLC30A8,
      encoding the zinc transporter ZnT8, associated with diabetes risk. A rare variant
      association study has now established the direction of effect, surprisingly
      showing that loss-of-function mutations in SLC30A8 are protective against
      diabetes. 

PMID- 24675526
TI  - Endothelial integrin alpha3beta1 stabilizes carbohydrate-mediated
      tumor/endothelial cell adhesion and induces macromolecular signaling complex
      formation at the endothelial cell membrane.
AB  - Blood borne metastatic tumor cell adhesion to endothelial cells constitutes a
      critical rate-limiting step in hematogenous cancer metastasis. Interactions
      between cancer associated carbohydrate Thomsen-Friedenreich antigen (TF-Ag) and
      endothelium-expressed galectin-3 (Gal-3) have been identified as the leading
      molecular mechanism initiating tumor/endothelial cell adhesion in several types
      of cancer. However, it is unknown how these rather weak and transient
      carbohydrate/lectin mediated interactions are stabilized. Here, using Western
      blot and LC tandem mass spectrometry analyses of pull-downs utilizing TF-Ag
      loaded gold nanoparticles, we identified Gal-3, endothelial integrin alpha3beta1,
      Src kinase, as well as 5 additional molecules mapping onto focal adhesion pathway
      as parts of the macromolecular complexes formed at the endothelial cell membranes
      downstream of TF-Ag/Gal-3 interactions. In a modified parallel flow chamber
      assay, inhibiting alpha3beta1 integrin greatly reduced the strength of
      tumor/endothelial cell interactions without affecting the initial cancer cell
      adhesion. Further, the macromolecular complex induced by TF-Ag/Gal-3/alpha3beta1
      interactions activates Src kinase, p38, and ERK1/2, pathways in endothelial cells
      in a time- and alpha3beta1-dependent manner. We conclude that, following the
      initial metastatic cell attachment to endothelial cells mediated by TF-Ag/Gal-3
      interactions, endothelial integrin alpha3beta1 stabilizes tumor/endothelial cell
      adhesion and induces the formation of macromolecular signaling complex activating
      several major signaling pathways in endothelial cells. 

PMID- 24675527
TI  - Outcome of single immediate implants placed in post-extraction infected and non
      infected sites, restored with cemented crowns: a 3-year prospective study.
AB  - OBJECTIVES: To compare the survival of immediate implants placed in
      postextraction infected and non-infected sites, restored with cemented crowns.
      METHODS: Thirty-six implants were immediately placed in non-infected sockets
      (control group (CG), n=18), and in infected alveoli (test group (TG), n=18) that
      had been debrided, curetted, cleaned with 90% hydrogen peroxide, irradiated with
      yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser, and irrigated with a sterile
      solution. Guided bone regeneration was performed under antibiotic coverture. All
      study patients had both a CG and a TG site. The implant osteotomy sites were
      extended 3-4 mm beyond the apical extent of the sockets to achieve primary
      stability for the implants. The prosthetic phase occurred 4.5 months after
      surgery. Success criteria were accepted as the presence of implant stability,
      absence of a radiolucent zone around the implants, absence of mucosal
      suppuration, and lack of pain. Clinical evaluations were performed at baseline,
      and at 12, 24, and 36 months of follow-up. RESULTS: All of the implants were
      osseointegrated 3 months after surgery. The 3-year survival rate was 94.44% for
      TG, and 100% for CG. The clinical and radiographic variables tested yielded no
      significant differences among groups at 36 months. CONCLUSIONS: Under the tested
      conditions, immediate implant placement can be considered a predictable treatment
      option for the restoration of fresh postextraction infected sockets. CLINICAL
      SIGNIFICANCE: Immediate implants may be indicated for replacing teeth lost due to
      chronic periapical lesions with endodontic failure history when appropriate
      preoperative procedures are taken to clean and decontaminate the surgical sites.

PMID- 24675528
TI  - Cloning and characterization of a novel Athspr promoter specifically active in
      vascular tissue.
AB  - The vascular system--xylem, phloem and the cambium--is essential for water
      supply, nutrient transport, and physical support in higher plants. Although it is
      known that vascular-specific gene expression is regulated by cis-acting
      regulatory sequences in promoters, it is largely unknown how many regulatory
      elements exist and what their roles are in promoters. To understand the
      regulatory elements of vascular-specific promoters and their roles in vascular
      development, a T-DNA insertion mutant showing delayed growth and diminished
      resistance to environmental stress was isolated using promoter trap strategy. The
      novel gene, Arabidopsis thaliana heat shock protein-related (Athspr), was cloned
      from Arabidopsis ecotype C24. Strong GUS (beta-glucuronidase) staining in the
      original promoter trap line was found in the vascular tissues of all organs in
      the mutant. The Athspr promoter was cloned and fused with GUS and eGFP (enhanced
      green fluorescent protein) reporter genes to verify its vascular-specific
      expression in Arabidopsis. Further histochemical analysis in transgenic plants
      demonstrated a similar GUS expression pattern in the vascular tissues. In
      addition, ATHSPR-eGFP driven by Athspr promoter was observed in vascular bundles
      of the transgenic seedling roots. Finally, comparative analysis with promoter
      motifs from 37 genes involved in vascular development revealed that Athspr and
      all other promoters active in vascular tissues contained regulatory elements
      responding to phytohormones, light, biotic and abiotic stresses, as well as those
      regulating tissue-specific expression. These results demonstrated that the Athspr
      promoter has a vascular tissue-specific activity and Athspr may have multiple
      functions in vascular development and resistance against various stresses.

PMID- 24675529
TI  - Molecular mechanisms underlying the divergent roles of SPARC in human
      carcinogenesis.
AB  - Communication between the cell and its surrounding environment, consisting of
      proteinaceous (non-living material) and extracellular matrix (ECM), is important
      for biophysiological and chemical signaling. This signaling results in a range of
      cellular activities, including cell division, adhesion, differentiation,
      invasion, migration and angiogenesis. The ECM non-structural secretory
      glycoprotein called secreted protein, acidic and rich in cysteine (SPARC), plays
      a significant role in altering cancer cell activity and the tumor's
      microenvironment (TME). However, the role of SPARC in cancer research has been
      the subject of controversy. This review mainly focuses on recent advances in
      understanding the contradictory nature of SPARC in relation to ECM assembly,
      cancer cell proliferation, adhesion, migration, apoptosis and tumor growth. 

PMID- 24675530
TI  - PLAGL2 regulates actin cytoskeletal architecture and cell migration.
AB  - Pleomorphic adenoma gene like-2 (PLAGL2), a member of the PLAG gene family, is a
      C2H2 zinc finger transcriptional factor that is involved in cellular
      transformation and apoptosis. In this report, we show that PLAGL2 is associated
      with the organization of stress fibers and with small guanosine triphosphatase
      (GTPase) activity. Depletion of PLAGL2 in two different ovarian cancer cell
      lines, ES-2 and HEY, induced activation of RhoA, whereas activity of Rac1 was
      suppressed. Organization of actin stress fibers and focal adhesions was
      significantly promoted by PLAGL2 knockdown in a RhoA-dependent manner.
      Conversely, exogenous expression of PLAGL2 in MDA-MB-231 cells, a breast cancer
      cell line, resulted in the activation of Rac1 and the inactivation of RhoA. In
      addition, PLAGL2 expression induced lamellipodia formation and disruption of
      stress fiber formation. Finally, we show that CHN1 expression is essential for
      Rac1 inactivation in PLAGL2-depleted cells. Our results demonstrate a crucial
      role of PLAGL2 in actin dynamics and give further insight into the role of PLAGL2
      in cellular transformation and apoptosis. 

PMID- 24675531
TI  - Crystal structure of human BS69 Bromo-ZnF-PWWP reveals its role in H3K36me3
      nucleosome binding.

PMID- 24675534
TI  - Small collaborative steps can add up to big change.

PMID- 24675532
TI  - Biomarker-guided sequential targeted therapies to overcome therapy resistance in
      rapidly evolving highly aggressive mammary tumors.
AB  - Combinatorial targeted therapies are more effective in treating cancer by
      blocking by-pass mechanisms or inducing synthetic lethality. However, their
      clinical application is hampered by resistance and toxicity. To meet this
      important challenge, we developed and tested a novel concept of biomarker-guided
      sequential applications of various targeted therapies using ErbB2
      overexpressing/PTEN-low, highly aggressive breast cancer as our model.
      Strikingly, sustained activation of ErbB2 and downstream pathways drives
      trastuzumab resistance in both PTEN-low/trastuzumab-resistant breast cancers from
      patients and mammary tumors with intratumoral heterogeneity from genetically
      engineered mice. Although lapatinib initially inhibited trastuzumab-resistant
      mouse tumors, tumors by-passed the inhibition by activating the PI3K/mTOR
      signaling network as shown by the quantitative protein arrays. Interestingly,
      activation of the mTOR pathway was also observed in neoadjuvant lapatinib-treated
      patients manifesting lapatinib resistance. Trastuzumab + lapatinib resistance was
      effectively overcome by sequential application of a PI3K/mTOR dual kinase
      inhibitor (BEZ235) with no significant toxicity. However, our p-RTK array
      analysis demonstrated that BEZ235 treatment led to increased ErbB2 expression and
      phosphorylation in genetically-engineered mouse tumors and in 3-D, but not 2-D,
      culture, leading to BEZ235 resistance. Mechanistically, we identified ErbB2
      protein stabilization and activation as a novel mechanism of BEZ235 resistance,
      which was reversed by subsequent treatment with lapatinib + BEZ235 combination.
      Remarkably, this sequential application of targeted therapies guided by biomarker
      changes in the tumors rapidly evolving resistance doubled the life-span of mice
      bearing exceedingly aggressive tumors. This fundamentally novel approach of using
      targeted therapies in a sequential order can effectively target and reprogram the
      signaling networks in cancers evolving resistance during treatment. 

PMID- 24675533
TI  - The mycetoma knowledge gap: identification of research priorities.
AB  - Mycetoma is a tropical disease which is caused by a taxonomically diverse range
      of actinomycetes (actinomycetoma) and fungi (eumycetoma). The disease was only
      recently listed by the World Health Organization (WHO) as a neglected tropical
      disease (NTD). This recognition is the direct result of a meeting held in Geneva
      on February 1, 2013, in which experts on the disease from around the world met to
      identify the key research priorities needed to combat mycetoma. The areas that
      need to be addressed are highlighted here. The initial priority is to establish
      the incidence and prevalence of the disease in regions where mycetoma is endemic,
      prior to determining the primary reservoirs of the predominant causal agents and
      their mode of transmission to susceptible individuals in order to establish novel
      interventions that will reduce the impact of the disease on individuals,
      families, and communities. Critically, economical, reliable, and effective
      methods are required to achieve early diagnosis of infections and consequential
      improved therapeutic outcomes. Molecular techniques and serological assays were
      considered the most promising in the development of novel diagnostic tools to be
      used in endemic settings. Improved strategies for treating eumycetoma and
      actinomycetoma are also considered. 

PMID- 24675536
TI  - Syringe driver safety issues: an update.

PMID- 24675535
TI  - Transforming children's palliative care through the International Children's
      Palliative Care Network.

PMID- 24675537
TI  - Specialist palliative care, non-cancer conditions, and guilt: an unholy triad?

PMID- 24675538
TI  - Breakthrough cancer pain: the role of the nurse.
AB  - Breakthrough pain is common in patients with cancer and is a significant cause of
      morbidity in this group of patients. Breakthrough pain is a heterogeneous
      condition, and so its management needs to be individualised. This paper describes
      the management of breakthrough pain and, specifically, the recently published
      guidelines of the European Oncology Nursing Society. 

PMID- 24675539
TI  - Assessment of the need for palliative care for children in South Africa.
AB  - UNICEF and the International Children's Palliative Care Network undertook a joint
      analysis in three sub-Saharan countries-Zimbabwe, South Africa, and Kenya-to
      estimate the palliative care need among their children and to explore these
      countries' capacities to deliver children's palliative care (CPC). This report
      concerns the findings from South Africa. The study adopted a cross-sectional
      mixed-methods approach using both quantitative and qualitative data obtained from
      primary and secondary sources. CPC need was estimated using prevalence and
      mortality statistics. The response to the need and existing gaps were analysed
      using data obtained from a literature review, interviews with key persons, and
      survey data from service providers.The findings show very limited CPC service
      coverage for children in the public sector. In addition, services are mainly
      localised, with minimal reach. Less than 5% of the children needing care in South
      Africa are receiving it, with those receiving it being closer to the end of life.
      Barriers to the delivery of CPC include fear of opioid use, lack of education on
      CPC, lack of integration into the primary care system, lack of policies on CPC,
      and lack of community and health professional awareness of CPC needs and
      services. Estimating the need for CPC is a critical step in meeting the needs of
      children with life-threatening conditions and provides a sound platform to
      advocate for closure of the unacceptably wide gaps in coverage. 

PMID- 24675540
TI  - Changes in symptom severity in Taiwanese lung cancer patients after gefitinib
      treatment: a pilot study.
AB  - AIM: The purpose of this study was to investigate symptom severity in advanced
      non-small cell lung cancer patients prior to gefitinib treatment and at 1-, 3-
      and 6-month intervals after starting treatment. METHODOLOGY: Fifty seven patients
      completed the Taiwanese version of the M.D. Anderson Symptom Inventory. The data
      were analysed using descriptive statistics, the Friedman non-parametric test, and
      Pearson correlation coefficients. RESULTS: Symptoms of nausea, difficulty
      remembering, lack of appetite, sadness, and vomiting increased at 1 month after
      treatment started, pain and shortness of breath increased at 3 months, and
      disturbed sleep, drowsiness, and numbness increased after 6 months. Fatigue and
      dry mouth increased at 3 months after treatment started and then decreased. Only
      distress decreased throughout the course of treatment. CONCLUSION: The findings
      may lead to the development of better clinical guidelines and improved
      information for patients on when to expect the greatest impact from their
      symptoms during the course of treatment.

PMID- 24675541
TI  - Perinatal palliative care: a developing specialty.
AB  - Neonates and babies have the highest death rate in the paediatric population.
      Perinatal palliative care aims to enhance the quality of life of babies with a
      life-limiting condition and their families. However, very little data is
      available on perinatal palliative care and its impact on babies and families
      along their journey. End-of-life decision-making for babies with an adverse
      prognosis also remains ethically challenging. This paper provides an overview of
      perinatal palliative care and its development, and then considers some of the
      issues affecting this field by looking at single national, institutional, and
      patient case studies. 

PMID- 24675542
TI  - First International Children's Palliative Care Network Conference.

PMID- 24675545
TI  - Scattering of massless Dirac fermions in circular p-n junctions with and without
      magnetic field.
AB  - In the absence of a magnetic field, a scattered wavefunction inside a circular p
      n junction in graphene exhibits an interference pattern with its high intensity
      maximum located around the caustics. We investigate the wavefunctions in the
      presence of a uniform magnetic field outside the circular region to show how the
      loci of the high intensity region changes by forming a Landau-level structure
      outside the circular region and a central high intensity region inside the
      circular p-n junction due to the strong reflection of massless Dirac fermions by
      the outside magnetic field. We conclude by suggesting experimental ways to detect
      such changes in pattern due to the effect of the magnetic field. 

PMID- 24675546
TI  - Resolving structural variability in network models and the brain.
AB  - Large-scale white matter pathways crisscrossing the cortex create a complex
      pattern of connectivity that underlies human cognitive function. Generative
      mechanisms for this architecture have been difficult to identify in part because
      little is known in general about mechanistic drivers of structured networks. Here
      we contrast network properties derived from diffusion spectrum imaging data of
      the human brain with 13 synthetic network models chosen to probe the roles of
      physical network embedding and temporal network growth. We characterize both the
      empirical and synthetic networks using familiar graph metrics, but presented here
      in a more complete statistical form, as scatter plots and distributions, to
      reveal the full range of variability of each measure across scales in the
      network. We focus specifically on the degree distribution, degree assortativity,
      hierarchy, topological Rentian scaling, and topological fractal scaling--in
      addition to several summary statistics, including the mean clustering
      coefficient, the shortest path-length, and the network diameter. The models are
      investigated in a progressive, branching sequence, aimed at capturing different
      elements thought to be important in the brain, and range from simple random and
      regular networks, to models that incorporate specific growth rules and
      constraints. We find that synthetic models that constrain the network nodes to be
      physically embedded in anatomical brain regions tend to produce distributions
      that are most similar to the corresponding measurements for the brain. We also
      find that network models hardcoded to display one network property (e.g.,
      assortativity) do not in general simultaneously display a second (e.g.,
      hierarchy). This relative independence of network properties suggests that
      multiple neurobiological mechanisms might be at play in the development of human
      brain network architecture. Together, the network models that we develop and
      employ provide a potentially useful starting point for the statistical inference
      of brain network structure from neuroimaging data.

PMID- 24675547
TI  - A transparent broadband ultrasonic detector based on an optical micro-ring
      resonator for photoacoustic microscopy.
AB  - Photoacoustic microscopy (PAM) does not rely on contrast agent to image the
      optical absorption contrast in biological tissue. It is uniquely suited for
      measuring several tissue physiological parameters, such as hemoglobin oxygen
      saturation, that would otherwise remain challenging. Researchers are designing
      new clinical diagnostic tools and multimodal microscopic systems around PAM to
      fully unleash its potential. However, the sizeable and opaque piezoelectric
      ultrasonic detectors commonly used in PAM impose a serious constraint. Our
      solution is a coverslip-style optically transparent ultrasound detector based on
      a polymeric optical micro-ring resonator (MRR) with a total thickness of 250 MUm.
      It enables highly-sensitive ultrasound detection over a wide receiving angle with
      a bandwidth of 140 MHz, which corresponds to a photoacoustic saturation limit of
      287 cm(-1), at an estimated noise-equivalent pressure (NEP) of 6.8 Pa. We also
      established a theoretical framework for designing and optimizing the MRR for PAM.

PMID- 24675548
TI  - Severe Allergic Contact Dermatitis From Temporary "Black Henna" Coloring of the
      Hair During Religious Cultural Celebrations: Three Different Cases, Same History.
AB  - Contact dermatitis after the application of temporary, paint-on, henna tattoos
      represents a well-known, potentially serious problem of active sensitization. We
      describe 3 cases involving 3 children of the same age who developed a severe
      contact dermatitis with massive face and neck swelling after application of black
      henna to their hair during "Purim" celebrations. All 3 cases had a history of
      having applied henna tattoos in the previous year with mild local reactions.
      Their reactions are presumed to be due to sensitization to para-phenylenediamine.
      Although reactions to henna are being increasingly reported, reactions of this
      severity seem to be rare and could lead to permanent skin changes. 

PMID- 24675549
TI  - Is R-CHOP Therapy a Lymphoma Growth Factor?
AB  - This article describes the first reported case of dramatic lymphocytosis flare
      after initiation of R-CHOP (rituximab, cyclophosphamide, doxorubicin,
      vincristine, and prednisone) therapy for an indolent lymphoma. The study patient
      exhibited a marginal zone lymphoma with mild nodal involvement but packed
      infiltration of the bone marrow. After initiation of RCHOP therapy, lymphocyte
      count increased from 329 to 707 * 109/L at day 7. Patient exhibited grade III
      infusion-related side effect during rituximab therapy. Lymphocyte flare was not
      accompanied with other clinical manifestation such as lymph node enlargement.
      Because patient's bone marrow aspirate showed a packed infiltration, it was
      hypothesized that lymphocytosis flare was a link to lymphocyte release from bone
      marrow and lymphocyte demargination. This report highlights the necessity to be
      vigilant after initiation of RCHOP therapy for lymphoma when pathologist notified
      a pack infiltration of the bone marrow.

PMID- 24675551
TI  - Letter to editor: A pilot study examining the role of regional cerebral oxygen
      saturation monitoring as a marker of return of spontaneous circulation in
      shockable (VF/VT) and non-shockable (PEA/asystole) cause of cardiac arrest.

PMID- 24675553
TI  - Ribosomal protein mutations in Korean patients with Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome
      characterized by hypoproliferative anemia, associated physical malformations and
      a predisposition to cancer. DBA has been associated with mutations and deletions
      in the large and small ribosomal protein genes, and genetic aberrations have been
      detected in ~50-60% of patients. In this study, nine Korean DBA patients were
      screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10,
      RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method. Mutations in
      RPS19, RPS26 and RPS17 were detected in four, two and one patient, respectively.
      Among the mutations detected in RPS19, two mutations were novel (c.26T>A, c.357
      2A>G). For the mutation-negative cases, array-CGH analysis was performed to
      identify copy-number variations, and no deletions involving the known DBA gene
      regions were identified. The relative mRNA expression of RPS19 estimated using
      real-time quantitative PCR analysis revealed two- to fourfold reductions in RPS19
      mRNA expression in three patients with RPS19 mutations, and p53 protein
      expression analysis by immunohistochemistry showed variable but significant
      nuclear staining in the DBA patients. In conclusion, heterozygous mutations in
      the known DBA genes RPS19, RPS26 and RPS17 were detected in seven out of nine
      Korean DBA patients. Among these patients, RPS19 was the most frequently mutated
      gene. In addition, decreased RPS19 mRNA expression and p53 overexpression were
      observed in the Korean DBA patients, which supports the hypothesis that
      haploinsufficiency and p53 hyperactivation represent a central pathway underlying
      the pathogenesis of DBA. 

PMID- 24675554
TI  - Analysis of trait mean and variability versus temperature in trematode cercariae:
      is there scope for adaptation to global warming?
AB  - The potential of species for evolutionary adaptation in the context of global
      climate change has recently come under scrutiny. Estimates of phenotypic
      variation in biological traits may prove valuable for identifying species, or
      groups of species, with greater or lower potential for evolutionary adaptation,
      as this variation, when heritable, represents the basis for natural selection.
      Assuming that measures of trait variability reflect the evolutionary potential of
      these traits, we conducted an analysis across trematode species to determine the
      potential of these parasites as a group to adapt to increasing temperatures.
      Firstly, we assessed how the mean number of infective stages (cercariae) emerging
      from infected snail hosts as well as the survival and infectivity of cercariae
      are related to temperature. Secondly and importantly in the context of
      evolutionary potential, we assessed how coefficients of variation for these
      traits are related to temperature, in both cases controlling for other factors
      such as habitat, acclimatisation, latitude and type of target host. With
      increasing temperature, an optimum curve was found for mean output and mean
      infectivity, and a linear decrease for survival of cercariae. For coefficients of
      variation, temperature was only an important predictor in the case of cercarial
      output, where results indicated that there is, however, no evidence for limited
      trait variation at the higher temperature range. No directional trend was found
      for either variation of survival or infectivity. These results, characterising
      general patterns among trematodes, suggest that all three traits considered may
      have potential to change through adaptive evolution.

PMID- 24675550
TI  - An evolutionary analysis of antigen processing and presentation across different
      timescales reveals pervasive selection.
AB  - The antigenic repertoire presented by MHC molecules is generated by the antigen
      processing and presentation (APP) pathway. We analyzed the evolutionary history
      of 45 genes involved in APP at the inter- and intra-species level. Results showed
      that 11 genes evolved adaptively in mammals. Several positively selected sites
      involve positions of fundamental importance to the protein function (e.g. the
      TAP1 peptide-binding domains, the sugar binding interface of langerin, and the
      CD1D trafficking signal region). In CYBB, all selected sites cluster in two loops
      protruding into the endosomal lumen; analysis of missense mutations responsible
      for chronic granulomatous disease (CGD) showed the action of different selective
      forces on the very same gene region, as most CGD substitutions involve aminoacid
      positions that are conserved in all mammals. As for ERAP2, different
      computational methods indicated that positive selection has driven the recurrent
      appearance of protein-destabilizing variants during mammalian evolution.
      Application of a population-genetics phylogenetics approach showed that purifying
      selection represented a major force acting on some APP components (e.g.
      immunoproteasome subunits and chaperones) and allowed identification of positive
      selection events in the human lineage. We also investigated the evolutionary
      history of APP genes in human populations by developing a new approach that uses
      several different tests to identify the selection target, and that integrates low
      coverage whole-genome sequencing data with Sanger sequencing. This analysis
      revealed that 9 APP genes underwent local adaptation in human populations. Most
      positive selection targets are located within noncoding regions with regulatory
      function in myeloid cells or act as expression quantitative trait loci.
      Conversely, balancing selection targeted nonsynonymous variants in TAP1 and CD207
      (langerin). Finally, we suggest that selected variants in PSMB10 and CD207
      contribute to human phenotypes. Thus, we used evolutionary information to
      generate experimentally-testable hypotheses and to provide a list of sites to
      prioritize in follow-up analyses. 

PMID- 24675555
TI  - From ancient to contemporary molecular eco-epidemiology of Chagas disease in the
      Americas.
AB  - One of the best-studied populations with regard to Chagas disease is from the
      coastal area of northern Chile at the foot of the western Andean slopes. The
      extremely arid climate here generates rapid, spontaneous desiccation of buried
      bodies, arresting the decay process. The absence of rainfall then preserves these
      dried bodies (mummies) for millennia. The aim of the present study was to perform
      the first molecular paleoepidemiological study on a set of 43 mummified human
      remains from the Atacama Desert in Northern Chile in order to elucidate the
      transmission dynamics and determinants of ancient genotypes, to try to unravel
      the natural history of the Trypanosoma cruzi taxon and Chagas disease.
      Interestingly, TcBat, a recently described Discrete Taxonomic Unit, emerges as
      the plausible ancestor of T. cruzi. The findings herein presented allow us to
      present a plausible model of T. cruzi transmission in pre-Columbian
      civilisations. 

PMID- 24675552
TI  - Gasdermin-B promotes invasion and metastasis in breast cancer cells.
AB  - Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four
      members (GSDMA-D). Gasdermin B expression has been detected in some tumor types
      such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has
      been related to tumor progression. At least four splicing isoforms of GSDMB have
      been identified, which may play differential roles in cancer. However, the
      implication of GSDMB in carcinogenesis and tumor progression is not well
      understood. Here, we uncover for the first time the functional implication of
      GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is
      correlated with reduced survival and increased metastasis in breast cancer
      patients included in an expression dataset (>1,000 cases). We demonstrate that
      GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being
      the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate
      the functional role of GSDMB in breast cancer two GSDMB isoforms were studied
      (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast
      carcinoma cell line promotes cell motility and invasion, while its silencing in
      HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype.
      Importantly, we demonstrate that both isoforms have a differential role on the
      activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB
      2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models
      as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms
      interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on
      this chaperone for its stability. Taken together, our results provide for the
      first time evidences that GSDMB-2 induces invasion, tumor progression and
      metastasis in MCF7 cells and that GSDMB can be considered as a new potential
      prognostic marker in breast cancer. 

PMID- 24675556
TI  - Trans-generational plasticity in physiological thermal tolerance is modulated by
      maternal pre-reproductive environment in the polychaete Ophryotrocha labronica.
AB  - Maternal temperature is known to affect many aspects of offspring phenotype, but
      its effect on offspring physiological thermal tolerance has received less
      attention, despite the importance of physiological traits in defining organismal
      ability to cope with temperature changes. To fill this gap, we used the marine
      polychaete Ophryotrocha labronica to investigate the influence of maternal
      temperature on offspring upper and lower thermal tolerance limits, and assess
      whether maternal influence changed according to the stage of offspring pre
      zygotic development at which a thermal cue was provided. Measurements were taken
      on adult offspring acclimated to 18 or 30 degrees C, produced by mothers
      previously reared at 24 degrees C and then exposed to 18 or 30 degrees C at an
      early and late stage of oogenesis. When the shift from 24 degrees C was provided
      early during oogenesis, mothers produced offspring with greater cold and heat
      tolerance whenever mother-offspring temperatures did not match, with respect to
      when they matched, suggesting the presence of an anticipatory maternal effect
      triggered by the thermal variation. Conversely, when the cue was provided later
      during oogenesis, more tolerant offspring were observed when temperatures
      persisted across generations. In this case, maternal exposure to 18 or 30 degrees
      C may have benefited offspring performance, while limitations in the transmission
      of the thermal cue may account for the lack of correlation between maternal
      experiences and offspring performance when mother-offspring environments did not
      match. Our results provided evidence for a trans-generational effect of
      temperature on physiological performance characterised by a high context
      dependency, and are discussed in the light of maternal pre-reproductive
      experiences. 

PMID- 24675557
TI  - Use of the swim bladder and lateral line in near-field sound source localization
      by fish.
AB  - We investigated the roles of the swim bladder and the lateral line system in
      sound localization behavior by the plainfin midshipman fish (Porichthys notatus).
      Reproductive female midshipman underwent either surgical deflation of the swim
      bladder or cryoablation of the lateral line and were then tested in a monopolar
      sound source localization task. Fish with nominally 'deflated' swim bladders
      performed similar to sham-deflated controls; however, post-experiment evaluation
      of swim bladder deflation revealed that a majority of 'deflated' fish (88%, seven
      of the eight fish) that exhibited positive phonotaxis had partially inflated swim
      bladders. In total, 95% (21/22) of fish that localized the source had at least
      partially inflated swim bladders, indicating that pressure reception is likely
      required for sound source localization. In lateral line experiments, no
      difference was observed in the proportion of females exhibiting positive
      phonotaxis with ablated (37%) versus sham-ablated (47%) lateral line systems.
      These data suggest that the lateral line system is likely not required for sound
      source localization, although this system may be important for fine-tuning the
      approach to the sound source. We found that midshipman can solve the 180 deg
      ambiguity of source direction in the shallow water of our test tank, which is
      similar to their nesting environment. We also found that the potential
      directional cues (phase relationship between pressure and particle motion) in
      shallow water differs from a theoretical free-field. Therefore, the general
      question of how fish use acoustic pressure cues to solve the 180 deg ambiguity of
      source direction from the particle motion vector remains unresolved. 

PMID- 24675558
TI  - Mexican blind cavefish use mouth suction to detect obstacles.
AB  - Fish commonly use their lateral line system to detect moving bodies such as prey
      and predators. A remarkable case is the Mexican blind cavefish Astyanax
      fasciatus, which evolved the ability to detect non-moving obstacles. The swimming
      body of A. fasciatus generates fluid disturbances, the alteration of which by an
      obstacle can be sensed by the fish's lateral line system. It is generally
      accepted that these alterations can provide information on the distance to the
      obstacle. We observed that A. fasciatus swimming in an unfamiliar environment
      open and close their mouths at high frequency (0.7-4.5 Hz) in order to generate
      suction flows. We hypothesized that repeated mouth suction generates a
      hydrodynamic velocity field, which is altered by an obstacle, inducing pressure
      gradients in the neuromasts of the lateral line and corresponding strong lateral
      line stimuli. We observed that the frequency and rate of mouth-opening events
      varied with the fish's distance to obstacles, a hallmark of pulse-based
      navigation mechanisms such as echolocation. We formulated a mathematical model of
      this hitherto unrecognized mechanism of obstacle detection and parameterized it
      experimentally. This model suggests that suction flows induce lateral line
      stimuli that are weakly dependent on the fish's speed, and may be an order of
      magnitude stronger than the correspondent stimuli induced by the fish's gliding
      body. We illustrate that A. fasciatus can navigate non-visually using a
      combination of two deeply ancestral and highly conserved mechanisms of ray-finned
      fishes: the mechanism of sensing water motion by the lateral line system and the
      mechanism of generating water motion by mouth suction. 

PMID- 24675559
TI  - Inhibition of photosynthetic CO2 fixation in the coral Pocillopora damicornis and
      its relationship to thermal bleaching.
AB  - Two inhibitors of the Calvin-Benson cycle [glycolaldehyde (GA) and potassium
      cyanide (KCN)] were used in cultured Symbiodinium cells and in nubbins of the
      coral Pocillopora damicornis to test the hypothesis that inhibition of the Calvin
      Benson cycle triggers coral bleaching. Inhibitor concentration range-finding
      trials aimed to determine the appropriate concentration to generate inhibition of
      the Calvin-Benson cycle, but avoid other metabolic impacts to the symbiont and
      the animal host. Both 3 mmol l(-1) GA and 20 MUmol l(-1) KCN caused minimal
      inhibition of host respiration, but did induce photosynthetic impairment,
      measured by a loss of photosystem II function and oxygen production. GA did not
      affect the severity of bleaching, nor induce bleaching in the absence of thermal
      stress, suggesting inhibition of the Calvin-Benson cycle by GA does not initiate
      bleaching in P. damicornis. In contrast, KCN did activate a bleaching response
      through symbiont expulsion, which occurred in the presence and absence of thermal
      stress. While KCN is an inhibitor of the Calvin-Benson cycle, it also promotes
      reactive oxygen species formation, and it is likely that this was the principal
      agent in the coral bleaching process. These findings do not support the
      hypothesis that temperature-induced inhibition of the Calvin-Benson cycle alone
      induces coral bleaching. 

PMID- 24675560
TI  - Growth hormone transgenesis and polyploidy increase metabolic rate, alter the
      cardiorespiratory response and influence HSP expression in response to acute
      hypoxia in Atlantic salmon (Salmo salar) yolk-sac alevins.
AB  - Growth hormone (GH)-transgenic Atlantic salmon display accelerated growth rates
      compared with non-transgenics. GH-transgenic fish also display cardiorespiratory
      and metabolic modifications that accompany the increased growth rate. An elevated
      routine metabolic rate has been described for pre- and post-smolt GH-transgenic
      salmon that also display improvements in oxygen delivery to support the increased
      aerobic demand. The early ontogenic effects of GH transgenesis on the respiratory
      and cellular physiology of fish, especially during adverse environmental
      conditions, and the effect of polyploidy are unclear. Here, we investigated the
      effects of GH transgenesis and polyploidy on metabolic, heart and ventilation
      rates and heat shock protein (HSP) levels after exposure to acute hypoxia in post
      hatch Atlantic salmon yolk-sac alevins. Metabolic rate decreased with decreasing
      partial pressures of oxygen in all genotypes. In normoxia, triploid transgenics
      displayed the highest mass-specific metabolic rates in comparison to diploid
      transgenics and non-transgenic triploids, which, in contrast, had higher rates
      than diploid non-transgenics. In hypoxia, we observed a lower mass-specific
      metabolic rate in diploid non-transgenics compared with all other genotypes.
      However, no evidence for improved O2 uptake through heart or ventilation rate was
      found. Heart rate decreased in diploid non-transgenics while ventilation rate
      decreased in both diploid non-transgenics and triploid transgenics in severe
      hypoxia. Regardless of genotype or treatment, inducible HSP70 was not expressed
      in alevins. Following hypoxia, the constitutive isoform of HSP70, HSC70,
      decreased in transgenics and HSP90 expression decreased in all genotypes. These
      data suggest that physiological changes through GH transgenesis and polyploidy
      are manifested during early ontogeny in Atlantic salmon. 

PMID- 24675561
TI  - Coloration principles of nymphaline butterflies - thin films, melanin,
      ommochromes and wing scale stacking.
AB  - The coloration of the common butterflies Aglais urticae (small tortoiseshell),
      Aglais io (peacock) and Vanessa atalanta (red admiral), belonging to the
      butterfly subfamily Nymphalinae, is due to the species-specific patterning of
      differently coloured scales on their wings. We investigated the scales'
      structural and pigmentary properties by applying scanning electron microscopy,
      (micro)spectrophotometry and imaging scatterometry. The anatomy of the wing
      scales appears to be basically identical, with an approximately flat lower lamina
      connected by trabeculae to a highly structured upper lamina, which consists of an
      array of longitudinal, parallel ridges and transversal crossribs. Isolated scales
      observed at the abwing (upper) side are blue, yellow, orange, red, brown or
      black, depending on their pigmentation. The yellow, orange and red scales contain
      various amounts of 3-OH-kynurenine and ommochrome pigment, black scales contain a
      high density of melanin, and blue scales have a minor amount of melanin pigment.
      Observing the scales from their adwing (lower) side always revealed a structural
      colour, which is blue in the case of blue, red and black scales, but orange for
      orange scales. The structural colours are created by the lower lamina, which acts
      as an optical thin film. Its reflectance spectrum, crucially determined by the
      lamina thickness, appears to be well tuned to the scales' pigmentary spectrum.
      The colours observed locally on the wing are also due to the degree of scale
      stacking. Thin films, tuned pigments and combinations of stacked scales together
      determine the wing coloration of nymphaline butterflies. 

PMID- 24675563
TI  - Moving without a purpose: an experimental study of swarm guidance in the Western
      honey bee, Apis mellifera.
AB  - During reproductive swarming, honey bee scouts perform two very important
      functions. Firstly, they find new nesting locations and return to the swarm
      cluster to communicate their discoveries. Secondly, once the swarm is ready to
      depart, informed scout bees act as guides, leading the swarm to its final
      destination. We have previously hypothesised that the two processes, selecting a
      new nest site and swarm guidance, are tightly linked in honey bees. When swarms
      can be laissez faire about where they nest, reaching directional consensus prior
      to lift off seems unnecessary. If, in contrast, it is essential that the swarm
      reaches a precise location, either directional consensus must be near unanimous
      prior to swarm departure or only a select subgroup of the scouts guide the swarm.
      Here, we tested experimentally whether directional consensus is necessary for the
      successful guidance of swarms of the Western honey bee Apis mellifera by forcing
      swarms into the air prior to the completion of the decision-making process. Our
      results show that swarms were unable to guide themselves prior to the swarm
      reaching the pre-flight buzzing phase of the decision-making process, even when
      directional consensus was high. We therefore suggest that not all scouts involved
      in the decision-making process attempt to guide the swarm. 

PMID- 24675562
TI  - Responses of Drosophila giant descending neurons to visual and mechanical
      stimuli.
AB  - In Drosophila, the paired giant descending neurons (GDNs), also known as giant
      fibers, and the paired giant antennal mechanosensory descending neurons (GAMDNs),
      are supplied by visual and mechanosensory inputs. Both neurons have the largest
      cell bodies in the brain and both supply slender axons to the neck connective.
      The GDN axon thereafter widens to become the largest axon in the thoracic
      ganglia, supplying information to leg extensor and wing depressor muscles. The
      GAMDN axon remains slender, interacting with other descending neuron axons
      medially. GDN and GAMDN dendrites are partitioned to receive inputs from antennal
      mechanosensory afferents and inputs from the optic lobes. Although GDN anatomy
      has been well studied in Musca domestica, less is known about the Drosophila
      homolog, including electrophysiological responses to sensory stimuli. Here we
      provide detailed anatomical comparisons of the GDN and the GAMDN, characterizing
      their sensory inputs. The GDN showed responses to light-on and light-off stimuli,
      expanding stimuli that result in luminance decrease, mechanical stimulation of
      the antennae, and combined mechanical and visual stimulation. We show that
      ensembles of lobula columnar neurons (type Col A) and mechanosensory antennal
      afferents are likely responsible for these responses. The reluctance of the GDN
      to spike in response to stimulation confirms observations of the Musca GDN. That
      this reluctance may be a unique property of the GDN is suggested by comparisons
      with the GAMDN, in which action potentials are readily elicited by mechanical and
      visual stimuli. The results are discussed in the context of descending pathways
      involved in multimodal integration and escape responses. 

PMID- 24675565
TI  - The length-force behavior and operating length range of squid muscle vary as a
      function of position in the mantle wall.
AB  - Hollow cylindrical muscular organs are widespread in animals and are effective in
      providing support for locomotion and movement, yet are subject to significant non
      uniformities in circumferential muscle strain. During contraction of the mantle
      of squid, the circular muscle fibers along the inner (lumen) surface of the
      mantle experience circumferential strains 1.3 to 1.6 times greater than fibers
      along the outer surface of the mantle. This transmural gradient of strain may
      require the circular muscle fibers near the inner and outer surfaces of the
      mantle to operate in different regions of the length-tension curve during a given
      mantle contraction cycle. We tested the hypothesis that circular muscle
      contractile properties vary transmurally in the mantle of the Atlantic longfin
      squid, Doryteuthis pealeii. We found that both the length-twitch force and length
      tetanic force relationships of the obliquely striated, central mitochondria-poor
      (CMP) circular muscle fibers varied with radial position in the mantle wall. CMP
      circular fibers near the inner surface of the mantle produced higher force
      relative to maximum isometric tetanic force, P0, at all points along the
      ascending limb of the length-tension curve than CMP circular fibers near the
      outer surface of the mantle. The mean +/- s.d. maximum isometric tetanic stresses
      at L0 (the preparation length that produced the maximum isometric tetanic force)
      of 212 +/- 105 and 290 +/- 166 kN m(-2) for the fibers from the outer and inner
      surfaces of the mantle, respectively, did not differ significantly (P=0.29). The
      mean twitch:tetanus ratios for the outer and inner preparations, 0.60 +/- 0.085
      and 0.58 +/- 0.10, respectively, did not differ significantly (P=0.67). The
      circular fibers did not exhibit length-dependent changes in contraction kinetics
      when given a twitch stimulus. As the stimulation frequency increased, L0 was
      approximately 1.06 times longer than LTW, the mean preparation length that
      yielded maximum isometric twitch force. Sonomicrometry experiments revealed that
      the CMP circular muscle fibers operated in vivo primarily along the ascending
      limb of the length-tension curve. The CMP fibers functioned routinely over muscle
      lengths at which force output ranged from only 85% to 40% of P0, and during
      escape jets from 100% to 30% of P0. Our work shows that the functional diversity
      of obliquely striated muscles is much greater than previously recognized.

PMID- 24675564
TI  - Upper body contributions to power generation during rapid, overhand throwing in
      humans.
AB  - High-speed and accurate throwing is a distinctive human behavior. Achieving fast
      projectile speeds during throwing requires a combination of elastic energy
      storage at the shoulder, as well as the transfer of kinetic energy from proximal
      body segments to distal segments. However, the biomechanical bases of these
      mechanisms are not completely understood. We used inverse dynamics analyses of
      kinematic data from 20 baseball players fitted with four different braces that
      inhibit specific motions to test a model of power generation at key joints during
      the throwing motion. We found that most of the work produced during throwing is
      generated at the hips, and much of this work (combined with smaller contributions
      from the pectoralis major) is used to load elastic elements in the shoulder and
      power the rapid acceleration of the projectile. Despite rapid angular velocities
      at the elbow and wrist, the restrictions confirm that much of the power generated
      to produce these distal movements comes from larger proximal segments, such as
      the shoulder and torso. Wrist hyperextension enhances performance only modestly.
      Together, our data also suggest that heavy reliance on elastic energy storage may
      help explain some common throwing injuries and can provide further insight into
      the evolution of the upper body and when our ancestors first developed the
      ability to produce high-speed throws. 

PMID- 24675566
TI  - Sequence of hole resonances in complex oxide heterostructures.
AB  - Resonant soft x-ray scattering measurements at the O K edge on Sr2CuO4
      nu/La2NiO4+delta (SCO/LNO) complex oxide superlattices show resonances for holes
      in the two constituent layers, in a sequence of energy levels. The observation of
      well defined resonances, on a superlattice with layers one unit cell thick,
      indicates that the resonance energy is largely unaffected by atoms outside a
      cluster extending half a unit cell along the c axis, consistent with calculations
      for bulk materials. Comparison to measurements on related superlattices confirms
      that the order of resonances at the O K edge reflects the order of hole ground
      state energies in the heterostructure buried layers. For the SCO/LNO
      superlattices, the measurements show that the ground-state energies remain
      different in very thin SCO and LNO layers, which is a contributing factor when
      considering electronic reconstruction at interfaces, in addition to the areal
      density of ionic charges in the atomic planes. Different hole energy levels in
      the SCO/LNO superlattice also imply that holes do not spread into SCO from LNO
      layers. 

PMID- 24675567
TI  - Soluble expression of Spinach psbC gene in Escherichia coli and in vitro
      reconstitution of CP43 coupled with chlorophyll a only.
AB  - CP43 is a chlorophyll a (Chl a) and beta-carotene (beta-Car) binding protein
      encoded by psbC gene. In this study, psbC gene isolated from Spinach was
      expressed in Escherichia coli in soluble state. After lysis of the cells, the
      apoproteins purified by nickel affinity chromatography were examined by SDS-PAGE
      and Western-blot. Next, reconstitution experiment was carried out in vitro and
      the formation of stable pigment-protein complex was analyzed by partially
      denaturing electrophoresis. After purifying reconstituted CP43 (rCP43) from free
      pigments (FPs) by sucrose gradient ultracentrifugation and subsequently ion
      exchange chromatography (IEC), the eluate was analyzed by partially denaturing
      electrophoresis to confirm stability of the reconstructed complex. Finally,
      analyses of spectroscopic character of the eluate revealed that in vitro
      reconstitution was achieved and FPs were completely removed from the pigment
      protein complex. Comparison between the absorption spectra of the rCP43 and
      native CP43 (nCP43) showed the lack of peaks between 450 and 500 nm, illustrating
      that the beta-Car was stripped off rCP43. In brief, it is feasible to obtain a
      reconstituted protein binding Chl a only, indicating that the occupancy of the
      beta-Car site has small impact on the stabilization of CP43. However, beta-Car
      shows strong interaction with Chl a, inducing the hyperchromic effect in blue
      region of spectrum and the blue shift of the 438.5 nm and 673.5 nm absorption
      band to 437 nm and 671 nm respectively. To some extent, our research is
      suggestive that beta-Car, coupled loosely with CP43, contributes to the precise
      orientation of Chl a in vivo. 

PMID- 24675568
TI  - The Role of STAT3 in Non-Small Cell Lung Cancer.
AB  - Persistent phosphorylation of signal transducer and activator of transcription 3
      (STAT3) has been demonstrated in 22%~65% of non-small cell lung cancers (NSCLC).
      STAT3 activation is mediated by receptor tyrosine kinases, such as epidermal
      growth factor receptor (EGFR) and MET, cytokine receptors, such as IL-6, and non
      receptor kinases, such as Src. Overexpression of total or phosphorylated STAT3 in
      resected NSCLC leads to poor prognosis. In a preclinical study, overexpression of
      STAT3 was correlated with chemoresistance and radioresistance in NSCLC cells.
      Here, we review the role of STAT3 and the mechanisms of treatment resistance in
      malignant diseases, especially NSCLC. As STAT3 is a critical mediator of the
      oncogenic effects of EGFR mutations, we discuss STAT3 pathways in EGFR-mutated
      NSCLC, referring to mechanisms of EGFR tyrosine kinase inhibitor resistance. 

PMID- 24675569
TI  - Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated
      Macrophages.
AB  - Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary
      brain malignancy. Failures of the traditional therapies in treating GBMs raise
      the urgent requirement to develop new approaches with more responsive targets.
      The phenomenon of the high infiltration of tumor-associated macrophages (TAMs)
      into GBMs has been observed for a long time. Regardless of the limited knowledge
      about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it
      possible to be a good target for GBM treatment. In this review, we discussed the
      unique features of TAMs in GBMs, including their origin, the tumor-supportive
      properties, the secreted cytokines, and the relevant mechanisms. In addition, we
      tried to interpret the current understandings about the interplay between GBM
      cancer cells and TAMs. Finally, the translational studies of targeting TAMs were
      also described. 

PMID- 24675570
TI  - HiJAK'd Signaling; the STAT3 Paradox in Senescence and Cancer Progression.
AB  - Clinical and epidemiological data have associated chronic inflammation with
      cancer progression. Most tumors show evidence of infiltrating immune and
      inflammatory cells, and chronic inflammatory disorders are known to increase the
      overall risk of cancer development. While immune cells are often observed in
      early hyperplastic lesions in vivo, there remains debate over whether these
      immune cells and the cytokines they produce in the developing hyperplastic
      microenvironment act to inhibit or facilitate tumor development. The interleukin
      6 (IL-6) family of cytokines, which includes IL-6 and oncostatin M (OSM), among
      others (LIF, CT-1, CNTF, and CLC), are secreted by immune cells, stromal cells,
      and epithelial cells, and regulate diverse biological processes. Each of the IL-6
      family cytokines signals through a distinct receptor complex, yet each receptor
      complex uses a shared gp130 subunit, which is critical for signal transduction
      following cytokine binding. Activation of gp130 results in the activation of
      Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen
      Activated Protein Kinase (MAPK) and Phosphatidylinositol 3-Kinase (PI3K)
      signaling cascades. Tumor suppressive signaling can often be observed in normal
      cells following prolonged STAT3 activation. However, there is mounting evidence
      that the IL-6 family cytokines can contribute to later stages of tumor
      progression in many ways. Here we will review how the microenvironmental IL-6
      family cytokine OSM influences each stage of the transformation process. We
      discuss the intrinsic adaptations a developing cancer cell must make in order to
      tolerate and circumvent OSM-mediated growth suppression, as well as the OSM
      effectors that are hijacked during tumor expansion and metastasis. We propose
      that combining current therapies with new ones that suppress the signals
      generated from the tumor microenvironment will significantly impact an
      oncologist's ability to treat cancer. 

PMID- 24675572
TI  - MRFalign: protein homology detection through alignment of Markov random fields.
AB  - Sequence-based protein homology detection has been extensively studied and so far
      the most sensitive method is based upon comparison of protein sequence profiles,
      which are derived from multiple sequence alignment (MSA) of sequence homologs in
      a protein family. A sequence profile is usually represented as a position
      specific scoring matrix (PSSM) or an HMM (Hidden Markov Model) and accordingly
      PSSM-PSSM or HMM-HMM comparison is used for homolog detection. This paper
      presents a new homology detection method MRFalign, consisting of three key
      components: 1) a Markov Random Fields (MRF) representation of a protein family;
      2) a scoring function measuring similarity of two MRFs; and 3) an efficient ADMM
      (Alternating Direction Method of Multipliers) algorithm aligning two MRFs.
      Compared to HMM that can only model very short-range residue correlation, MRFs
      can model long-range residue interaction pattern and thus, encode information for
      the global 3D structure of a protein family. Consequently, MRF-MRF comparison for
      remote homology detection shall be much more sensitive than HMM-HMM or PSSM-PSSM
      comparison. Experiments confirm that MRFalign outperforms several popular HMM or
      PSSM-based methods in terms of both alignment accuracy and remote homology
      detection and that MRFalign works particularly well for mainly beta proteins. For
      example, tested on the benchmark SCOP40 (8353 proteins) for homology detection,
      PSSM-PSSM and HMM-HMM succeed on 48% and 52% of proteins, respectively, at
      superfamily level, and on 15% and 27% of proteins, respectively, at fold level.
      In contrast, MRFalign succeeds on 57.3% and 42.5% of proteins at superfamily and
      fold level, respectively. This study implies that long-range residue interaction
      patterns are very helpful for sequence-based homology detection. The software is
      available for download at http://raptorx.uchicago.edu/download/. A summary of
      this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5. 

PMID- 24675571
TI  - Sex differences in overall and cause-specific mortality among HIV-infected adults
      on antiretroviral therapy in Europe, Canada and the US.
AB  - BACKGROUND: Here, we aimed to evaluate regional differences in all-cause, AIDS-
      and non-AIDS-related mortality in HIV-positive men and women started on
      combination antiretroviral therapy (cART) in Europe, Canada and the US. METHODS:
      The ART Cohort Collaboration (ART-CC) combines 19 cohorts of individuals started
      on cART in Europe and North America (NA). We analysed patients infected via
      injecting drug use (IDU) or heterosexual sex using Cox proportional hazards
      models. RESULTS: A total of 32,443 European (45.9% women), 1,162 (32.5% women)
      Canadian and 2,721 (15.5% women) US patients were included. In Europe and NA,
      women were younger, more likely to have acquired HIV heterosexually, be AIDS-free
      and have higher CD4(+) T-cell counts and lower HIV-1 RNA at baseline. European
      women had lower rates of all-cause (adjusted hazard ratio: 0.76; 95% CI 0.68,
      0.84) and non-AIDS mortality (0.67; 0.57, 0.78) than men, but AIDS-mortality
      rates were similar (0.90; 0.75, 1.09). Women had lower mortality due to non-AIDS
      infections (0.6 versus 1.3 per 1,000 person-years), liver diseases (0.4 versus
      1.7), non-AIDS malignancies (0.6 versus 2.0) and cardiovascular diseases (0.6
      versus 1.0). Between-sex differences in all-cause mortality were larger in
      heterosexuals (0.70; 0.61, 0.80) than in IDU (0.88; 0.73, 1.05; interaction P
      value =0.043). No sex differences in all-cause mortality were found in Canada
      (hazard ratio women 1.13; 0.82, 1.56) or US (hazard ratio women 1.12; 0.79,
      1.58). CONCLUSIONS: The increasing importance of non-AIDS mortality is leading to
      emergent sex differences among HIV-positive patients in Europe, as in the general
      population. Despite the better clinical characteristics at cART initiation, women
      in NA had similar mortality to men.

PMID- 24675574
TI  - Host use patterns by the European woodwasp, Sirex noctilio, in its native and
      invaded range.
AB  - Accelerating introductions of forest insects challenge decision-makers who might
      or might not respond with surveillance programs, quarantines, eradication
      efforts, or biological control programs. Comparing ecological controls on
      indigenous vs. introduced populations could inform responses to new
      introductions. We studied the European woodwasp, Sirex noctilio, which is not a
      pest in its native forests, is a serious invasive pest in the southern
      hemisphere, and now has an uncertain future in North America after its
      introduction there. Indigenous populations of S. noctilio (in Galicia, Spain)
      resembled those in New York in that S. noctilio were largely restricted to
      suppressed trees that were also dying for other reasons, and still only some
      dying trees showed evidence of S. noctilio: 20-40% and 35-51% in Galicia and New
      York, respectively. In both areas, P. sylvestris (native to Europe) was the
      species most likely to have attacks in non-suppressed trees. P. resinosa, native
      to North America, does not appear dangerously susceptible to S. noctilio. P.
      radiata, which sustains high damage in the southern hemisphere, is apparently not
      innately susceptible because in Galicia it was less often used by native S.
      noctilio than either native pine (P. pinaster and P. sylvestris). Silvicultural
      practices in Galicia that maintain basal area at 25-40 m(2)/ha limit S. noctilio
      abundance. More than 25 species of other xylophagous insects feed on pine in
      Galicia, but co-occurrences with S. noctilio were infrequent, so strong
      interspecific competition seemed unlikely. Evidently, S. noctilio in northeastern
      North America will be more similar to indigenous populations in Europe, where it
      is not a pest, than to introduced populations in the southern hemisphere, where
      it is. However, S. noctilio populations could behave differently when they reach
      forests of the southeastern U.S., where tree species, soils, climate, ecology,
      management, and landscape configurations of pine stands are different.

PMID- 24675573
TI  - Visceral leishmaniasis outbreak in South Sudan 2009-2012: epidemiological
      assessment and impact of a multisectoral response.

PMID- 24675575
TI  - Is this an infected liver cyst?

PMID- 24675576
TI  - Hepatitis C virus replication compartment formation: mechanism and drug target.

PMID- 24675577
TI  - A prospective evaluation of posterior capsule opacification in eyes with diabetes
      mellitus: a case-control study.
AB  - AIM: To compare the development of posterior capsule opacification (PCO) between
      eyes with and without diabetes mellitus after single-piece hydrophobic acrylic
      intraocular lens implantation 4 years postoperatively. METHODS: In this
      prospective, observational case-control study carried out at Iladevi Cataract and
      IOL Research Centre, Ahmedabad, India, 75 consecutive eyes with diabetes mellitus
      (cases) were compared with 75 age-matched eyes with age-related cataract
      (controls). A detailed, preoperative and posterior segment evaluation was carried
      out in eyes with diabetes mellitus to detect the presence or absence of diabetic
      retinopathy (DR). The Mann-Whitney U-test was applied to compare the differences
      in the development of PCO between the two groups. RESULTS: There was no
      difference in median PCO between cases and controls at 1 month (2.0 vs 1.50,
      P<0.068), but cases had a higher median PCO at 12 months (2.95 vs 1.30, P<0.001).
      At 4 years, there was no significant difference in median PCO between cases and
      controls (3.75 vs 2.25, P=0.273). The duration of diabetes increased the
      incidence of PCO at 4 years (P=0.02). Severity of DR had no influence on the
      progress of PCO at 4 years (P=0.69). CONCLUSION: Diabetes mellitus did not
      increase the incidence of PCO at 4 years. The duration of diabetes increased the
      risk of PCO. The severity of retinopathy did not influence the development of
      PCO.

PMID- 24675578
TI  - 'Double occlusion': black Artisan iris claw intraocular lens insertion following
      failed occlusion treatment for intractable diplopia.

PMID- 24675579
TI  - Anomalies in drug choice in glaucoma clinics.

PMID- 24675580
TI  - Chorioretinal coloboma in a paediatric population.
AB  - AIM: To determine the validity of laser photocoagulation as a prophylactic
      treatment in the prevention of rhegmatogenous retinal detachment (RRD) in a group
      of paediatric patients presenting with chorioretinal coloboma. METHODS:
      Observational case series of consecutive patients aged 0-15 years with
      chorioretinal coloboma seen in a tertiary eye hospital were reviewed. Data were
      analysed with SPSS version 16, a P-value of <0.05 was considered significant.
      RESULTS: One hundred and ninety-eight patients (335 eyes) were identified. The
      prevalence of retinal detachment and ocular anomalies was 17.6 and 87.2%,
      respectively. Ocular anomalies included iris coloboma (71%), microcornea (45.1%),
      nystagmus (41.5%), strabismus (21.2%), and microphthalmos (19.1%). The prevalence
      of retinal detachment was 2.9% in those eyes that received prophylactic laser
      photocoagulation, whereas the risk of retinal detachment was 24.1% in eyes left
      untreated. Post-operative complications following retinal detachment surgery
      occurred in 86.7% eyes; the most frequent being recurrent retinal detachment
      (53.8%). The mean duration of follow-up was 1.59 +/- 0.21 years (0-7 years) and
      0.79 +/- 0.16 years (0-8 years) in the group that had laser and in those that
      were treatment naive, respectively. CONCLUSIONS: Prophylactic laser treatment
      appears to have a protective effect for the prevention of RRD in eyes with
      chorioretinal coloboma. Measures towards prophylactic therapy should be
      instituted to reduce the risk of retinal detachment in choroid colobomatous eyes
      due to the problems in the management of these retinal detachments.

PMID- 24675581
TI  - Double port injector device to reduce endothelial damage in DMEK.
AB  - OBJECTIVE: To study endothelial injury from a newly designed asymmetric double
      port Descemet Membrane Endothelial Keratoplasty (DMEK) injector, both ex-vivo and
      in clinical practice. DESIGN: Laboratory investigation with an interventional
      case series study. METHOD: Sixteen rabbit endothelial rolls were tested for
      injection using a no-touch technique. For each pair of rolls, one endothelial
      graft underwent injection with a single port Pasteur pipette twice, wheras the
      other was injected with a novel asymmetric double port injector with a larger
      diameter entry port than the exit port also twice. Each graft was stained with 4
      6-diamidino-2-phenylinidole dihydrochloride and was counted under a fluorescence
      inverted microscope before and after injection. The proportion of graft injury
      was calculated and the differences were analyzed. Subsequently, six patients
      requiring DMEK underwent surgery using this novel insertion device and
      endothelial cell loss was calculated 3 months after the surgery. RESULTS: After
      injection, the mean proportion of endothelial cell survival with the single port
      pipette was 78.8% (n=8; SD: +/-20.9%), whereas the double port injector yielded a
      survival rate of 96.8% (n=8; SD: +/-8.4%). This difference was statistically
      significant (P=0.008), representing less endothelial injury with the double port
      device. Early endothelial cell loss after 3 months in the DMEK patients was 26.1%
      (SD: +/-6.1%). CONCLUSION: In our injection model, using a double port injector
      created significantly less endothelial cell damage than with the single port
      pipette. Clinically, this device yielded early endothelial cell loss comparable
      to that of the series performed by experienced DMEK surgeons.

PMID- 24675582
TI  - Scleral suture-fixated intraocular lens explantation.

PMID- 24675583
TI  - Higher intraocular pressure is associated with leukoaraiosis among middle-aged
      and elderly Koreans without glaucoma or dementia.
AB  - AIM: Leukoaraiosis and high intraocular pressure are strongly associated with
      cardiovascular disease, vascular angiopathy, and geriatric syndrome. Until now,
      little is known about the relationship between intraocular pressure and
      leukoaraiosis in its preclinical stage. The aim of this study was to evaluate the
      association between intraocular pressure and leukoaraiosis among middle-aged and
      elderly Koreans without glaucoma or dementia. METHODS: We examined the
      relationship of intraocular pressure with leukoaraiosis at a preclinical stage in
      753 Korean adults (474 men, 279 women; mean age 57.8 +/- 6.6 years). A multiple
      logistic regression analysis was performed in order to determine whether
      intraocular pressure is an independent determinant for leukoaraiosis. RESULTS:
      The overall prevalence of leukoaraiosis was 7.3%. Mean ocular pressure (+/-SD)
      was significantly higher in the leukoaraiosis group than the control group (14.3
      +/- 2.9 and 13.5 +/- 2.9, respectively; P=0.028). In multiple logistic regression
      analysis, the odds ratio for leukoaraiosis was 1.18 (95% confidence interval:
      1.06-1.31) for each 1 mm Hg increase in intraocular pressure. CONCLUSION:
      Intraocular pressure was found to be independently and positively associated with
      leukoaraiosis. This finding indicates that higher intraocular pressure may be a
      useful additional measure in assessing the risk of leukoaraiosis in the clinical
      setting.

PMID- 24675584
TI  - Urrets-Zavalia syndrome as a complication of ocular hypotonia due to intravenous
      cidofovir treatment.

PMID- 24675585
TI  - Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in
      HIV-infected adults.
AB  - OBJECTIVE: In settings of high HIV prevalence, tuberculosis control and patient
      management are hindered by lack of accurate, rapid tuberculosis diagnostic tests
      that can be performed at point-of-care. The Determine TB LAM Ag (TB LAM) test is
      a lateral flow immunochromatographic test for detection of mycobacterial
      lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and
      specificity of the TB LAM test for tuberculosis diagnosis. DESIGN: Prospective
      diagnostic accuracy study. SETTING: Hospital and outpatient settings in Uganda
      and South Africa. PARTICIPANTS: HIV-infected adults with tuberculosis symptoms
      and/or signs. METHODS: Participants provided a fresh urine specimen for TB LAM
      testing, blood for mycobacterial culture, and 2 respiratory specimens for smear
      microscopy and mycobacterial culture. MAIN OUTCOME MEASURES: For the TB LAM test,
      sensitivity in participants with culture-positive tuberculosis and specificity in
      participants without tuberculosis. RESULTS: A total of 1013 participants were
      enrolled. Among culture-positive tuberculosis patients, the TB LAM test
      identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4
      <=100 cells per cubic millimeter. The test was specific in 559/573 (97.6%)
      patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum
      smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with
      CD4 <=100. CD4 <=50 [adjusted odds ratio (AOR), 6.2; P < 0.001] or 51-100 (AOR,
      7.1; P < 0.001), mycobacteremia (AOR, 6.1; P < 0.01) and hospitalization (AOR,
      2.6; P = 0.03) were independently associated with a positive TB LAM test.
      CONCLUSIONS: In HIV-positive adults with CD4 <=100, the TB LAM urine test
      detected over half of culture-positive tuberculosis patients, in <30 minutes and
      without the need for equipment or reagents.

PMID- 24675586
TI  - Cryptococcal meningitis management in Tanzania with strict schedule of serial
      lumber punctures using intravenous tubing sets: an operational research study.
AB  - BACKGROUND: Cryptococcal meningitis (CM) has a mortality rate of ~70% among HIV
      infected adults in low-income countries. Controlling intracranial pressure (ICP)
      is essential in CM, but it is difficult in low-income countries because
      manometers and practical ICP management protocols are lacking. METHODS: As part
      of a continuous quality improvement project, our Tanzanian hospital initiated a
      new protocol for ICP management for CM. All adult inpatients with CM are included
      in a prospective patient registry. At the time of analysis, this registry
      included data from 2 years before the initiation of this new ICP management
      protocol and for a 9-month period after. ICP was measured at baseline and at days
      3, 7, and 14 by both manometer and intravenous (IV) tubing set. All patients were
      given IV fluconazole according to Tanzanian treatment guidelines and were
      followed until 30 days after admission. RESULTS: Among adult inpatients with CM,
      32 of 35 patients (91%) had elevated ICP on admission. Cerebrospinal fluid
      pressure measurements using the improvised IV tubing set demonstrated excellent
      agreement (r = 0.96) with manometer measurements. Compared with historical
      controls, the new ICP management protocol was associated with a significant
      reduction in 30-day mortality (16/35 [46%] vs. 48/64 [75%] in historical
      controls; hazard ratio = 2.1 [95% CI: 1.1 to 3.8]; P = 0.018]. CONCLUSIONS:
      Increased ICP is almost universal among HIV-infected adults admitted with CM in
      Tanzania. Intensive ICP management with a strict schedule of serial lumbar
      punctures reduced in-hospital mortality compared with historical controls. ICP
      measurement with IV tubing sets may be a good alternative in resource-limited
      health facilities where manometers are not available.

PMID- 24675588
TI  - Implementation of a collaborative HIV testing model between an emergency
      department and infectious disease clinic.

PMID- 24675589
TI  - Charge-density analysis using multipolar atom and spherical charge models: 2
      methyl-1,3-cyclopentanedione, a compound displaying a resonance-assisted hydrogen
      bond.
AB  - The experimental charge-density distribution in 2-methyl-1,3-cyclopentanedione in
      the crystal state was analyzed by synchrotron X-ray diffraction data collection
      at 0.33 A resolution. The molecule in the crystal is in the enol form. The
      experimental electron density was refined using the Hansen-Coppens multipolar
      model and an alternative modeling, based on spherical atoms and additional
      charges on the covalent bonds and electron lone-pair sites. The crystallographic
      refinements, charge-density distributions, molecular electrostatic potentials,
      dipole moments and intermolecular interaction energies obtained from the
      different charge-density models were compared. The experimental results are also
      compared with the theoretical charge densities using theoretical structure
      factors obtained from periodic quantum calculations at the B3LYP/6-31G** level. A
      strong intermolecular O-H...O hydrogen bond connects molecules along the [001]
      direction. The deformation density maps show the resonance within the O=C-C=C-OH
      fragment and merged lone pair lobes on the hydroxyl O atom. This resonance is
      further confirmed by the analysis of charges and topology of the electron
      density.

PMID- 24675587
TI  - Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS
      NHL.
AB  - OBJECTIVE: To determine if changes in levels of serum microRNAs (miRNAs) were
      seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).
      DESIGN: Serum miRNA levels were compared in 3 subject groups from the Multicenter
      AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not
      develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62,
      median time before diagnosis, 8.8 months). METHODS: A total of 175 serum-enriched
      miRNAs were initially screened to identify differentially expressed miRNAs among
      these groups and the results validated by quantitative polymerase chain reaction.
      Receiver-operating characteristic analysis was then performed to assess biomarker
      utility. RESULTS: Higher levels of miR-21 and miR-122, and a lower level of miR
      223, were able to discriminate HIV-infected from the HIV-uninfected groups,
      suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS
      NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able
      to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous
      system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop
      NHL, with area under the receiver-operating characteristic curve of 0.777 and
      0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for
      PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%,
      respectively. CONCLUSIONS: Altered serum levels of miR-21, miR-122, and miR-223
      are seen in HIV-infected individuals. Higher serum level of miR-222 has clear
      potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV
      infected individuals.

PMID- 24675590
TI  - LiZn(4 - x) (x = 0.825) as a (3 + 1)-dimensional modulated derivative of
      hexagonal close packing.
AB  - The (3+1)-dimensional modulated structure of the LiZn(4 - x) (x = 0.825) binary
      compound has been determined in the superspace. The compound crystallizes in the
      orthorhombic superspace group Cmcm(alpha00)0s0 with a = 2.7680 (6), b = 4.7942
      (6), c = 4.3864 (9) A, modulation wavevector: q ? 4/7a*. The structure is a
      derivative from the hexagonal close packing. The cubo-octahedron as a
      coordination polyhedron (c.n. = 12) is typical for all atoms. Bonding between
      atoms is explored by means of the TB-LMTO-ASA program package. The absence of
      strong interatomic interactions in LiZn(4 - x) is the main reason for the
      possible structure transformations.

PMID- 24675591
TI  - M(m)H(n)(XO4)((m+n)/2) crystals: structure, phase transitions, hydrogen bonds,
      conductivity. I. K9H7(SO4)8.H2O crystals--a new representative of the family of
      solid acid conductors.
AB  - To reveal the structural conditionality for anomalies in physical properties,
      including dielectric and optical properties, diffraction studies of
      K9H7(SO4)8.H2O crystals were performed using synchrotron radiation in the
      temperature range 293-450 K and determined at 405 K, taking H atoms into account.
      The results indicate that the occurrence of high conductivity in K9H7(SO4)8.H2O
      crystals with a temperature increase is associated with the outward diffusion of
      water molecules, hydrogen-bond network rearrangement and the formation of
      channels for the possible motion of K(+) ions. A rearranged system of hydrogen
      bonds consists of permanent bonds and partly of dynamically disordered bonds.
      Hydrogen-bond rearrangement and the hindered back diffusion of water to the
      crystal bulk stabilize the high-temperature crystal structure right down to room
      temperature. 

PMID- 24675593
TI  - X-ray crystal structures of Al-doped (Y,Ca)Ba2Cu3O(7-y) whiskers.
AB  - Al(+3)-doped (Y,Ca)Ba2Cu3O(7-y) (YBCO) whiskers have been synthesized using a
      solid-state reaction technique. These materials are promising candidates for
      solid-state THz applications based on sequences of Josephson Junctions (IJJs).
      Alumina addition was systematically varied and the effect of aluminium
      incorporation on the structure has been investigated using single-crystal X-ray
      diffraction. Aluminium only replaces Cu atoms in the O-Cu-O-Cu chains and a
      gradual transition from orthorhombic to tetragonal space group occurs, thus
      increasing the Al content. A gradual modification of the coordination sphere of
      the copper site has also been observed. The Ca(2+) ion substitutes mainly the
      Y(3+) ion and also, to a small extent, the Ba(2+) ion.

PMID- 24675592
TI  - Calcium carbonate microparticle growth controlled by a conjugate drug-copolymer
      and crystallization time.
AB  - The influence of crystallization reaction time on CaCO3 microparticle growth from
      supersaturate aqueous solutions, in the presence of a conjugate drug-copolymer,
      has been investigated. The polymer conjugate, P(NVP-MA-Ox), is based on poly(N
      vinylpyrrolidone-co-maleic anhydride) as the support and 2-amino-5-(4
      methoxyphenyl)-1,3,4-oxadiazole as the drug. The microparticles are characterized
      by optical, scanning and transmission electron microscopy, dynamic light
      scattering, X-ray diffraction, flow particle image analysis and particle charge
      density. X-ray diffraction (XRD) investigations showed that calcite polymorph
      content increased with an increase in crystallization time, even if the
      electrostatic interactions between Ca(2+) and polyanionic sites of P(NVP-MA-Ox)
      structure conduct to an increased vaterite phase stability. The strong particle
      size increase after 6 h of ageing can be ascribed to partially vaterite
      recrystallization and adsorption of nano-scaled calcite crystallite nuclei at
      microparticles surfaces. The pH stability of the particles was shown by zeta
      potential changes and their adsorption capacity as a function of their
      composition, and characteristics were tested using methylene blue. The sorption
      capacity of composite materials was strongly influenced by the ratio between
      polymorphs in the composites, and increased with the increase of calcite content
      and ageing time. 

PMID- 24675594
TI  - Superspace description of wagnerite-group minerals (Mg,Fe,Mn)2(PO4)(F,OH).
AB  - Reinvestigation of more than 40 samples of minerals belonging to the wagnerite
      group (Mg, Fe, Mn)2(PO4)(F,OH) from diverse geological environments worldwide,
      using single-crystal X-ray diffraction analysis, showed that most crystals have
      incommensurate structures and, as such, are not adequately described with known
      polytype models (2b), (3b), (5b), (7b) and (9b). Therefore, we present here a
      unified superspace model for the structural description of periodically and
      aperiodically modulated wagnerite with the (3+1)-dimensional superspace group
      C2/c(0beta0)s0 based on the average triplite structure with cell parameters a ?
      12.8, b ? 6.4, c ? 9.6 A, beta ? 117 degrees  and the modulation vectors q =
      betab*. The superspace approach provides a way of simple modelling of the
      positional and occupational modulation of Mg/Fe and F/OH in wagnerite. This
      allows direct comparison of crystal properties. 

PMID- 24675595
TI  - Assessing the performance of density functional theory in optimizing molecular
      crystal structure parameters.
AB  - This paper assesses the performance of plane-wave density functional theory
      calculations at returning reliable structural information for molecular crystal
      structures where the primary intermolecular interactions are either hydrogen
      bonding or dispersion interactions. The computed structures are compared with
      input structures obtained from the Cambridge Structural Database, and assessed in
      terms of crystal packing similarities, unit-cell volume and shape, short contact
      distances and hydrogen-bond distances. The results demonstrate that the PBE
      functional [Perdew, Burke & Ernzerhof (1996). Phys. Rev. Lett. 77, 3865-3868]
      with Tkatchenko and Scheffler's 'TS' dispersion correction [Tkatchenko &
      Scheffler (2009). Phys. Rev. Lett. 102, 073005] is capable of returning reliable
      full structural optimizations, in which both atomic positions and unit-cell
      vectors are free to optimize simultaneously. 

PMID- 24675596
TI  - Monoclinic superstructure in orthorhombic Ce10W22O81 from transmission electron
      microscopy.
AB  - A complex rare-earth tungstate structure, present in a two-phased powder, was
      solved by electron diffraction, precession and high-resolution electron
      microscopy. The orthorhombic space group Pbnm and the atomic positions deduced
      from X-ray diffraction experiments were confirmed for Ce10W22O81. A C2/c
      monoclinic superstructure, with cell parameters a = 7.8, b = 36.1, c = 22.2 A and
      beta = 100.2 degrees , was shown and attributed to a partial oxidation of Ce(3+)
      leading to interstitial oxygen ions. 

PMID- 24675597
TI  - Structure refinement of the delta1p phase in the Fe-Zn system by single-crystal X
      ray diffraction combined with scanning transmission electron microscopy.
AB  - The structure of the delta1p phase in the iron-zinc system has been refined by
      single-crystal synchrotron X-ray diffraction combined with scanning transmission
      electron microscopy. The large hexagonal unit cell of the delta1p phase with the
      space group of P63/mmc comprises more or less regular (normal) Zn12 icosahedra,
      disordered Zn12 icosahedra, Zn16 icosioctahedra and dangling Zn atoms that do not
      constitute any polyhedra. The unit cell contains 52 Fe and 504 Zn atoms so that
      the compound is expressed with the chemical formula of Fe13Zn126. All Fe atoms
      exclusively occupy the centre of normal and disordered icosahedra. Iron-centred
      normal icosahedra are linked to one another by face- and vertex-sharing forming
      two types of basal slabs, which are bridged with each other by face-sharing with
      icosioctahedra, whereas disordered icosahedra with positional disorder at their
      vertex sites are isolated from other polyhedra. The bonding features in the
      delta1p phase are discussed in comparison with those in the Gamma and zeta phases
      in the iron-zinc system. 

PMID- 24675598
TI  - Average structures of the disordered beta-phase of Pigment Red 170: a single
      crystal X-ray diffraction study.
AB  - The beta-phase of the industrially important Pigment Red 170 (beta-P.R. 170) has
      a structure with severe layer stacking disorder. The single-crystal X-ray
      diffraction pattern consists of a difficult-to-disentangle mix of Bragg
      diffraction superimposed on rods of diffuse scattering which impede the
      estimation of accurate Bragg intensities. Two average monoclinic structure models
      with the same unit-cell dimensions, but different extents of disorder in the
      layers and different space groups seem plausible, one with the non-conventional
      space group setting B2(1)/g (No. 14, Z' = 2) and one in P2(1)/a (No. 14, Z' = 4).
      Disordered molecules related by a translation of 0.158b are present in all layers
      of the B2(1)/g model and in every second layer of the P2(1)/a model. Layer-to
      layer contacts are practically the same in both models. According to order
      disorder theory, both models are valid superposition structures. Structure-factor
      calculations show that the pattern of strong and weak Bragg reflections is very
      similar for the two models. R factors indicate that the B2(1)/g model is the most
      economic representation of the average structure. However, given the limitations
      in data processing, the P2(1)/a model should not be discarded and further insight
      sought from a detailed analysis of the experimental diffuse scattering. The
      difficulties encountered in this analysis raise the question of whether or not
      the concept of an average structure is applicable in practice to beta-P.R. 170.

PMID- 24675599
TI  - Explanation of the stacking disorder in the beta-phase of Pigment Red 170.
AB  - The beta-phase of Pigment Red 170, C26H22N4O4, which is used industrially for the
      colouration of plastics, crystallizes in a layer structure with stacking
      disorder. The disorder is characterized by a lateral translational shift between
      the layers with a component ty of either +0.421 or -0.421. Order-disorder (OD)
      theory is used to derive the possible stacking sequences. Extensive lattice
      energy minimizations were carried out on a large set of structural models with
      different stacking sequences, containing up to 2688 atoms. These calculations
      were used to determine the actual local structures and to derive the stacking
      probabilities. It is shown that local structures and energies depend not only on
      the arrangement of neighbouring layers, but also next-neighbouring layers. Large
      models with 100 layers were constructed according to the derived stacking
      probabilities. The diffraction patterns simulated from those models are in good
      agreement with the experimental single-crystal and powder diffraction patterns.
      Electron diffraction investigation on a nanocrystalline industrial sample
      revealed the same disorder. Hence the lattice-energy minimizations are able to
      explain the disorder and the diffuse scattering. 

PMID- 24675600
TI  - High-temperature structural study of decagonal Al-Cu-Rh.
AB  - The structure of decagonal Al-Cu-Rh has been studied as a function of temperature
      by in-situ single-crystal X-ray diffraction in order to contribute to the
      discussion on energy or entropy stabilization of quasicrystals. The experiments
      were performed at 293, 1223, 1153, 1083 and 1013 K. A common subset of 1460
      unique reflections was used for the comparative structure refinements at each
      temperature. A comparison of the high-temperature datasets suggests that the best
      quasiperiodic ordering should exist between 1083 and 1153 K. However, neither the
      refined structures nor the phasonic displacement parameter vary significantly
      with temperature. This indicates that the phasonic contribution to entropy does
      not seem to play a major role in the stability of this decagonal phase in
      contrast to other kinds of structural disorder, which suggests that, in this
      respect, this decagonal phase would be similar to other complex intermetallic
      high-temperature phases. 

PMID- 24675601
TI  - The quasiperiodic average structure of highly disordered decagonal Zn-Mg-Dy and
      its temperature dependence.
AB  - A single-crystal X-ray diffraction structure analysis of decagonal Zn-Mg-Dy, a
      Frank-Kasper-type quasicrystal, was performed using the higher-dimensional
      approach. For this first Frank-Kasper (F-K) decagonal quasicrystal studied so
      far, significant differences to the decagonal Al-TM-based (TM: transition metal)
      phases were found. A new type of twofold occupation domain is located on certain
      edge centers of the five-dimensional unit cell. The structure can be described in
      terms of a two-cluster model based on a decagonal cluster (~ 23 A diameter)
      arranged on the vertices of a pentagon-Penrose tiling (PPT) and a star-like
      cluster covering the remaining space. This model is used for the five-dimensional
      refinements, which converged to an R value of 0.126. The arrangement of clusters
      is significantly disordered as indicated by high-angle annular dark-field
      scanning transmission electron microscopy (HAADF-STEM). In order to check the
      structure and stability at higher temperatures, in-situ high-temperature (HT)
      single-crystal X-ray diffraction experiments were conducted at 598 and 648 K
      (i.e. slightly below the decomposition temperature). The structure does not
      change significantly, however, the best quasiperiodic order is found at 598 K.
      The implication of these results on the stabilization mechanism of quasicrystals
      is discussed. 

PMID- 24675602
TI  - Topological analysis of electron density and the electrostatic properties of
      isoniazid: an experimental and theoretical study.
AB  - Isoniazid (isonicotinohydrazide) is an important first-line antitubercular drug
      that targets the InhA enzyme which synthesizes the critical component of the
      mycobacterial cell wall. An experimental charge-density analysis of isoniazid has
      been performed to understand its structural and electronic properties in the
      solid state. A high-resolution single-crystal X-ray intensity data has been
      collected at 90 K. An aspherical multipole refinement was carried out to explore
      the topological and electrostatic properties of the isoniazid molecule. The
      experimental results were compared with the theoretical charge-density
      calculations performed using CRYSTAL09 with the B3LYP/6-31G** method. A
      topological analysis of the electron density reveals that the Laplacian of
      electron density of the N-N bond is significantly less negative, which indicates
      that the charges at the b.c.p. (bond-critical point) of the bond are least
      accumulated, and so the bond is considered to be weak. As expected, a strong
      negative electrostatic potential region is present in the vicinity of the O1, N1
      and N3 atoms, which are the reactive locations of the molecule. The C-H...N, C
      H...O and N-H...N types of intermolecular hydrogen-bonding interactions stabilize
      the crystal structure. The topological analysis of the electron density on
      hydrogen bonding shows the strength of intermolecular interactions.

PMID- 24675603
TI  - Structure determination of three polymorphs of xylazine from laboratory powder
      diffraction data.
AB  - The crystal structures of three xylazine hydrochloride [N-(2,6-dimethylphenyl)
      5,6-dihydro-4H-1,3-thiaz-2-amine hydrochloride] polymorphs A, Z and X have been
      solved from powder diffraction data and refined using Rietveld refinement. Data
      were obtained with Cu Kalpha radiation. All polymorphs were found to have
      structures with Z' = 1 and Z = 4. All the structures determined contained strong
      hydrogen bonds between the amino groups and chloride anions. The crystal
      structures of forms A and X featured pi-pi stacking interactions. 

PMID- 24675604
TI  - Structure determination from powder data without prior indexing, using a
      similarity measure based on cross-correlation functions.
AB  - A method to refine organic crystal structures from powder diffraction data with
      incorrect lattice parameters has been developed. The method is based on the
      similarity measure developed by de Gelder et al. [J. Comput. Chem. (2001), 22,
      273-289], using the cross- and auto-correlation functions of a simulated and an
      experimental powder pattern. The lattice parameters, molecular position,
      molecular orientation and selected intramolecular degrees of freedom are
      optimized until the similarity measure reaches a maximum; subsequently, a
      Rietveld refinement is carried out. The program FIDEL (FIt with DEviating Lattice
      parameters) implements this method. The procedure is also suitable for unindexed
      powder data, powder diagrams of very low quality and powder diagrams of non-phase
      pure samples. Various applications are shown, including structure determinations
      from powder data using crystal structure predictions by standard force-field
      methods. Other useful applications include the automatic structure determination
      from powder data starting from the crystal structures of isostructural compounds
      (e.g. a solvate, hydrate or chemical derivative), or from crystal data measured
      at a different temperature or pressure. 

PMID- 24675605
TI  - Structure determination of KLaS2, KPrS2, KEuS2, KGdS2, KLuS2, KYS2, RbYS2, NaLaS2
      and crystal-chemical analysis of the group 1 and thallium(I) rare-earth sulfide
      series.
AB  - One of the purposes of this work is to provide a crystallographic review of group
      1 and thallium rare-earth ternary sulfides M(+)Ln(3+)S2. We have therefore
      determined crystal structures of KLaS2, KPrS2, KEuS2, KGdS2, KLuS2, KYS2, RbYS2,
      which belong to the alpha-NaFeO2 structural family (R3m), as well as NaLaS2,
      which is derived from the disordered NaCl structural type (Fm3m). The determined
      structures were compared with known members of the group 1 as well as thallium(I)
      rare-earth sulfides by the standard tools of crystal-chemical analysis such as
      comparison of bond-valences, analysis of interatomic distances and comparison of
      the unit-cell parameters. The results indicate why the cubic structural type is
      limited to Li(+) and Na(+) members of the series only. The analysis has also
      revealed frequent problems in the reported crystal structures, especially in the
      determination of the K(+) compounds, probably due to severe absorption and
      different accuracy and sensitivity of various instruments. Intense diffuse
      scattering has been discovered in NaLaS2, which will be the subject of further
      investigation. The newly determined as well as already known structures are
      summarized, together with critical comments about possible errors in the previous
      structure determinations.

PMID- 24675606
TI  - Strong positive and negative deviations from Vegard's rule: X-ray powder
      investigations of the three quasi-binary phase systems BiSX(1 - x)Y(x) (X, Y =
      Cl, Br, I).
AB  - Three quasi-binary phase systems, BiSX(1 - x)Y(x) (X, Y = Cl, Br, I; 0 < x < 1),
      have been investigated by X-ray powder diffraction. All three systems show
      unlimited solubility. For BiSCl(1 - x)Br(x) and BiSCl(1 - x)I(x), strong positive
      and negative deviations from Vegard's rule are observed with respect to the
      lattice parameters a and c. They are qualitatively explained by the asymmetry of
      the X coordination polyhedron and by anion-anion repulsions. For x < 0.32 [x >
      0.32] the BiSCl(1 - x)I(x) system mimics the behaviour of the BiSCl(1 - y)Br(y)
      [BiSBr(1 - y)I(y)] system (0 < y < 1).

PMID- 24675607
TI  - Comparison of the structural motifs and packing arrangements of six novel
      derivatives and one polymorph of 2-(1-phenyl-1H-1,2,3-triazol-4-yl)pyridine.
AB  - The crystal structures of a new polymorph and seven new derivatives of 2-(1
      phenyl-1H-1,2,3-triazol-4-yl)pyridine have been characterized and examined along
      with three structures from the literature to identify trends in their
      intermolecular contact patterns and packing arrangements in order to develop an
      insight into the crystallization behaviour of this class of compound. Seven
      unique C-H...X contacts were identified in the structures and three of these are
      present in four or more structures, indicating that these are reliable
      supramolecular synthons. Analysis of the packing arrangements of the molecules
      using XPac identified two closely related supramolecular constructs that are
      present in eight of the 11 structures; in all cases, the structures feature at
      least one of the three most common intermolecular contacts, suggesting a clear
      relationship between the intermolecular contacts and the packing arrangements of
      the structures. Both the intermolecular contacts and packing arrangements appear
      to be remarkably consistent between structures featuring different functional
      groups, with the expected exception of the carboxylic acid derivative 4-(4
      (pyridin-2-yl)-1H-1,2,3-triazol-1-yl) benzoic acid (L11), where the introduction
      of a strong hydrogen-bonding group results in a markedly different supramolecular
      structure being adopted. The occurrence of these structural features has been
      compared with the packing efficiency of the structures and their melting points
      in order to assess the relative favourability of the supramolecular structural
      features in stabilizing the crystal structures.

PMID- 24675608
TI  - X-ray resonant single-crystal diffraction technique, a powerful tool to
      investigate the kesterite structure of the photovoltaic Cu2ZnSnS4 compound.
AB  - Cu/Zn disorder in the kesterite Cu2ZnSnS4 derivatives used for thin film based
      solar cells is an important issue for photovoltaic performances. Unfortunately,
      Cu and Zn cannot be distinguished by conventional laboratory X-ray diffraction.
      This paper reports on a resonant diffraction investigation of a Cu2ZnSnS4 single
      crystal from a quenched powdered sample. The full disorder of Cu and Zn in the z
      = 1/4 atomic plane is shown. The structure, namely disordered kesterite, is then
      described in the I42m space group.

PMID- 24675609
TI  - Complete crystal structure of decafluorocyclohex-1-ene at 4.2 K from original
      neutron diffraction data.
AB  - The crystal structure model of decafluorocyclohex-1-ene at 4.2 K derived from
      simulated powder diffraction data and solid-state energy minimization [Smrcok et
      al. (2013). Acta Cryst. B69, 395-404] is found to be incomplete. In this study it
      is completed by an additional alternative molecular orientation revealed from the
      difference density analysis and direct space search. The structure is refined by
      the derivative difference method in the rigid-body approximation leading to
      perfect agreement between observed and calculated neutron powder patterns. 

PMID- 24675610
TI  - PSSP-RFE: accurate prediction of protein structural class by recursive feature
      extraction from PSI-BLAST profile, physical-chemical property and functional
      annotations.
AB  - Protein structure prediction is critical to functional annotation of the
      massively accumulated biological sequences, which prompts an imperative need for
      the development of high-throughput technologies. As a first and key step in
      protein structure prediction, protein structural class prediction becomes an
      increasingly challenging task. Amongst most homological-based approaches, the
      accuracies of protein structural class prediction are sufficiently high for high
      similarity datasets, but still far from being satisfactory for low similarity
      datasets, i.e., below 40% in pairwise sequence similarity. Therefore, we present
      a novel method for accurate and reliable protein structural class prediction for
      both high and low similarity datasets. This method is based on Support Vector
      Machine (SVM) in conjunction with integrated features from position-specific
      score matrix (PSSM), PROFEAT and Gene Ontology (GO). A feature selection
      approach, SVM-RFE, is also used to rank the integrated feature vectors through
      recursively removing the feature with the lowest ranking score. The definitive
      top features selected by SVM-RFE are input into the SVM engines to predict the
      structural class of a query protein. To validate our method, jackknife tests were
      applied to seven widely used benchmark datasets, reaching overall accuracies
      between 84.61% and 99.79%, which are significantly higher than those achieved by
      state-of-the-art tools. These results suggest that our method could serve as an
      accurate and cost-effective alternative to existing methods in protein structural
      classification, especially for low similarity datasets. 

PMID- 24675611
TI  - Effect of growth conditions on microbial activity and iron-sulfide production by
      Desulfovibrio vulgaris.
AB  - Sulfate-reducing bacteria (SRB) can produce iron sulfide (FeS) solids with
      mineralogical characteristics that may be beneficial for a variety of
      biogeochemical applications, such as long-term immobilization of uranium. In this
      study, the growth and metabolism of Desulfovibrio vulgaris, one of the best
      studied SRB species, were comprehensively monitored in batch studies, and the
      biogenic FeS solids were characterized by X-ray diffraction. Controlling the pH
      by varying the initial pH, the iron-to-sulfate ratio, or the electron donor -
      affected the growth of D. vulgaris and strongly influenced the formation and
      growth of FeS solids. In particular, lower pH (from initial conditions or a
      decrease caused by less sulfate reduction, FeS precipitation, or using pyruvate
      as the electron donor) produced larger-sized mackinawite (Fe1+xS). Greater
      accumulation of free sulfide, from more sulfate reduction by D. vulgaris, also
      led to larger-sized mackinawite and particularly stimulated mackinawite
      transformation to greigite (Fe3S4) when the free sulfide concentration was
      29.3mM. Furthermore, sufficient free Fe(2+) led to the additional formation of
      vivianite [Fe3(PO4)2.8(H2O)]. Thus, microbially relevant conditions (initial pH,
      choice of electron donor, and excess or deficiency of sulfide) are tools to
      generate biogenic FeS solids of different characteristics. 

PMID- 24675612
TI  - Role of iron in H(2)S emission behavior during the decomposition of biodegradable
      substrates in landfill.
AB  - Hydrogen sulfide (H2S) is regarded as a major odor causing compound in landfill
      gas that may lead to adverse environmental and health effects. In this study, the
      potential role of iron in the entire life cycle of H2S production and emission
      was investigated during the decomposition of biodegradable substrates in the
      landfilled refuse. The results showed that the quantity of H2S emission decreased
      about 95% when Fe(OH)3 was present in the biodegradable sulfur-containing
      substrates. During this degradation process, a lot of sulfide was generated,
      which was present mostly as ferrous sulfide. In addition, a total of 7.68% S-H2S
      of total sulfur released as gas phase could be remained in solid-liquid phase
      effectively in the simulated substrates with iron. Thus, using the appropriate
      way to take advantage of iron "hidden" in the landfilled refuse might be a good
      choice for in situ control of H2S emission. Moreover, if this high level of iron
      is not presented, landfill odor pollution might become more serious. 

PMID- 24675613
TI  - Degradation of pentachlorophenol by hydroxyl radicals and sulfate radicals using
      electrochemical activation of peroxomonosulfate, peroxodisulfate and hydrogen
      peroxide.
AB  - The present study is to investigate the reactivity of free radicals (SO4(-) and
      HO) generated from common oxidants (peroxomonosulfate (PMS), peroxodisulfate
      (PDS) and hydrogen peroxide (HP)) activated by electrochemically generated
      Fe(2+)/Fe(3+) ions which furthermore are evaluated to destroy pentachlorophenol
      (PCP) in aqueous solution. The effect of solution pH and amount of oxidants (PMS,
      PDS and HP) in electrocoagulation (EC) on PCP degradation is analyzed in detail.
      The experimental results reveal that, optimum initial solution pH is 4.5 and PMS
      is more efficient oxidant addition in EC. 75% PCP degradation is achieved at
      60min electrolysis time from PMS assisted EC. According to the first order rate
      constant, faster PCP degradation rate is obtained by PMS assisted EC. The PCP
      degradation rate by oxidant assisted EC is observed in the following order:
      EC/PMS>EC/PDS>EC/HP>EC. Further to identify the influences of experimental
      factors involved in PCP degradation by oxidant assisted EC, an experimental
      design based on an orthogonal array (OA) L9 (3(3)) is proposed using Taguchi
      method. The factors that most significantly affect the process robustness are
      identified as A (oxidant) and B (pH) which together account for nearly 86% of the
      variance. 

PMID- 24675614
TI  - Using combined bio-omics methods to evaluate the complicated toxic effects of
      mixed chemical wastewater and its treated effluent.
AB  - Mixed chemical wastewaters (MCWW) from industrial park contain complex mixtures
      of trace contaminants, which cannot be effectively removed by wastewater
      treatment plants (WWTP) and have become an unignored threat to ambient
      environment. However, limited information is available to evaluate the
      complicated toxic effects of MCWW and its effluent from wastewater treatment
      plant (WTPE) from the perspective of bio-omics. In this study, mice were exposed
      to the MCWW and WTPE for 90 days and distinct differences in the hepatic
      transcriptome and serum metabolome were analyzed by digital gene expression (DGE)
      and proton nuclear magnetic resonance ((1)H-NMR) spectra, respectively. Our
      results indicated that disruption of lipid metabolism in liver and hepatotoxicity
      were induced by both MCWW and WTPE exposure. WTPE is still a health risk to the
      environment, which is in need of more attention. Furthermore, we demonstrated the
      potential ability of bio-omics approaches for evaluating toxic effects of MCWW
      and WTPE. 

PMID- 24675618
TI  - A multi-trait, meta-analysis for detecting pleiotropic polymorphisms for stature,
      fatness and reproduction in beef cattle.
AB  - Polymorphisms that affect complex traits or quantitative trait loci (QTL) often
      affect multiple traits. We describe two novel methods (1) for finding single
      nucleotide polymorphisms (SNPs) significantly associated with one or more traits
      using a multi-trait, meta-analysis, and (2) for distinguishing between a single
      pleiotropic QTL and multiple linked QTL. The meta-analysis uses the effect of
      each SNP on each of n traits, estimated in single trait genome wide association
      studies (GWAS). These effects are expressed as a vector of signed t-values (t)
      and the error covariance matrix of these t values is approximated by the
      correlation matrix of t-values among the traits calculated across the SNP (V).
      Consequently, t'V-1t is approximately distributed as a chi-squared with n degrees
      of freedom. An attractive feature of the meta-analysis is that it uses estimated
      effects of SNPs from single trait GWAS, so it can be applied to published data
      where individual records are not available. We demonstrate that the multi-trait
      method can be used to increase the power (numbers of SNPs validated in an
      independent population) of GWAS in a beef cattle data set including 10,191
      animals genotyped for 729,068 SNPs with 32 traits recorded, including growth and
      reproduction traits. We can distinguish between a single pleiotropic QTL and
      multiple linked QTL because multiple SNPs tagging the same QTL show the same
      pattern of effects across traits. We confirm this finding by demonstrating that
      when one SNP is included in the statistical model the other SNPs have a non
      significant effect. In the beef cattle data set, cluster analysis yielded four
      groups of QTL with similar patterns of effects across traits within a group. A
      linear index was used to validate SNPs having effects on multiple traits and to
      identify additional SNPs belonging to these four groups. 

PMID- 24675615
TI  - Genetic heterogeneity in a large cohort of Indian type 3 von Willebrand disease
      patients.
AB  - BACKGROUND: Though von Willebrand disease (VWD) is a common coagulation disorder,
      due to the complexity of the molecular analysis of von Willebrand factor gene
      (VWF), not many reports are available from this country. Large size of the gene,
      heterogeneous nature of mutations and presence of a highly homologous pseudogene
      region are the major impediments in the genetic diagnosis of VWD. The study is
      aimed at unravelling the molecular pathology in a large series of VWD patients
      from India using an effective strategy. METHOD: We evaluated 85 unrelated Indian
      type 3 VWD families to identify the molecular defects using a combination of
      techniques i.e. PCR-RFLP, direct DNA sequencing and multiple ligation probe
      amplification (MLPA). RESULTS: Mutations could be characterized in 77 unrelated
      index cases (ICs). 59 different mutations i.e. nonsense 20 (33.9%), missense 13
      (22%), splice site 4 (6.8%), gene conversions 6 (10.2%), insertions 2 (3.4%),
      duplication 1 (1.7%), small deletions 10 (17%) and large deletions 3 (5.1%) were
      identified, of which 34 were novel. Two common mutations i.e. p.R1779* and
      p.L970del were identified in our population with founder effect. Development of
      alloantibodies to VWF was seen in two patients, one with nonsense mutation
      (p.R2434*) and the other had a large deletion spanning exons 16-52. CONCLUSION:
      The molecular pathology of a large cohort of Indian VWD patients could be
      identified using a combination of techniques. A wide heterogeneity was observed
      in the nature of mutations in Indian VWD patients.

PMID- 24675619
TI  - Ordering dynamics in collectively swimming Surf Scoters.
AB  - One striking feature of collective motion in animal groups is a high degree of
      alignment among individuals, generating polarized motion. When order is lost, the
      dynamic process of reorganization, directly resulting from the individual
      interaction rules, provides significant information about both the nature of the
      rules, and how these rules affect the functioning of the collective. By analyzing
      trajectories of collectively swimming Surf Scoters (Melanitta perspicillata)
      during transitions between order and disorder, I find that individual speed and
      polarization are positively correlated in time, such that individuals move more
      slowly in groups exhibiting lower alignment. A previously validated zone-based
      model framework is used to specify interactions that permit repolarization while
      maintaining group cohesion and avoiding collisions. Polarization efficiency is
      optimized under the constraints of cohesion and collision-avoidance for alignment
      dominated propulsion (versus autonomous propulsion), and for repulsion an order
      of magnitude larger than attraction and alignment. The relative strengths of
      interactions that optimize polarization also quantitatively recover the speed
      polarization dependence observed in the data. Parameters determined here through
      optimizing polarization efficiency are essentially the same as those determined
      previously from a different approach: a best-fit model for polarized Surf Scoter
      movement data. The rules governing these flocks are therefore robust, accounting
      for behavior across a range of order and structure, and also highly responsive to
      perturbation. Flexibility and efficient repolarization offers an adaptive
      explanation for why specific interactions in such animal groups are used. 

PMID- 24675620
TI  - TIBS: a web database to browse gene expression in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder.
      Its symptoms include chronic abdominal pain, bloating gas, diarrhea and
      constipation. Many IBS patients also have psychological symptoms like depression
      or anxiety. These unpleasant symptoms significantly lower patients' quality of
      life. The prevalence of IBS in Europe and North America is about 10-15% of the
      population, which makes IBS a disorder with a high social cost. The
      pathophysiology of IBS is considered to be multifactorial and the exact cause of
      the disease remains poorly understood. Recently, a genome-wide expression
      microarray technique has been applied to investigate the possible mechanisms of
      IBS. However, a user-friendly database that allows scientists without
      bioinformatics background to query gene expression levels in these data sets and
      compare gene expression patterns across different tissues has not yet been
      established. Therefore, we have integrated four public expression microarray data
      (320 samples) from the Gene Expression Omnibus (GEO) and ArrayExpress databases
      into an online database called Transcriptome of Irritable Bowel Syndrome (TIBS).
      The gene expression change in IBS patients compared to healthy volunteers or UC
      patients in jejunum, sigmoid colon, rectum, and descending colon can be queried
      by gene symbols. Users can compare gene expression levels of IBS patients across
      these tissues. Sex difference of gene expression in IBS patients was also shown
      in the database. The current version of TIBS database contains 42,400 annotated
      gene probe sets represented on the Affymetrix Human Genome U133 plus 2.0
      platform. TIBS will be an invaluable resource for a better understanding of the
      pathogenesis of IBS at the molecular level and for drug development. The TIBS
      database is available online at http://www.chengfeng.info/tibs_database.html. 

PMID- 24675621
TI  - The relationship between ecology and the optimal helping strategy in cooperative
      breeders.
AB  - Cooperative breeding is a social system in which certain individuals
      (auxiliaries) postpone or forgo their own reproduction to help other individuals
      (breeders). The selective advantage for this behaviour has been considerably
      debated, but that debate has focused on models that neglect long-term
      evolutionary dynamics. As a result, there is little theoretical understanding of
      how system ecology relates to either optimal strategies or the scope for breeder
      auxiliary conflict. In this paper, we construct an explicit population model of
      cooperative breeding when help is under either maternal and auxiliary control,
      and obtain an ecologically-specific optimal strategy. Our optimal strategy
      reveals that there is a critical point at which helpers are no longer 'making the
      best of a bad situation', and are instead exploiting the breeders. The critical
      value at which this occurs delineates two qualitatively different ecological
      regimes. We also show that ecologies with constraints upon becoming a breeder, or
      unappealing aspects of being a breeder (e.g. high breeder mortality), minimize
      breeder-auxiliary conflict, whereas when there are appealing aspects (e.g. low
      breeder mortality) and few constraints, breeder-auxiliary conflict is maximized. 

PMID- 24675622
TI  - Writing is not just for other people!

PMID- 24675624
TI  - Reemergence of vitamin K deficiency bleeding.

PMID- 24675625
TI  - Use of benzodiazepines as anxiolytics in neonates: are we there yet?
AB  - Few controlled trials exist to demonstrate the efficacy and the risks of
      pharmacologic agents used in treating pediatric, and more specifically neonatal
      patients. It is not different for the central nervous system altering class of
      drugs, benzodiazepines (BZDs). Little information is known about the long-term
      effects of BZDs use in neonates as anxiolytics and sedatives causing trepidation
      with their use in the clinical setting. Insufficient data related to the use of
      BZDs result in a lack of clear recommendations to guide caregivers at the bedside
      on the safest administration patterns to avoid long-term adverse effects.
      However, caring for ill neonates, in particular surgical patients and infants
      requiring prolonged hospitalizations, necessitates the use of these agents. A
      literature search within the electronic database, PubMed, of English language,
      full-text articles published between 2007 and 2012 was undertaken to determine
      the state of the science regarding the use of BZDs in neonates. These medications
      cause unwanted effects in neonates with immature hepatic function (primary site
      of metabolism) and during a developmental period of tremendous neuroplasticity.
      It benefits caregivers to recognize the need for improved monitoring of stress
      experienced by infants in the NICU and understand the impact of prolonged
      agitation and subacute pain on infant development. 

PMID- 24675627
TI  - Probiotic guideline for necrotizing enterocolitis prevention in very low-birth
      weight neonates.
AB  - Necrotizing enterocolitis (NEC) is a gastrointestinal emergency that leads to
      inflammation and intestinal necrosis. Although probiotics can decrease the
      incidence of NEC, consistent recommendations for probiotic administration to very
      low-birth-weight (VLBW) neonates are lacking. Here, the best available evidence
      is reviewed and a practice guideline for probiotic administrations to VLBW
      neonates is described. A systematic review was conducted using MEDLINE and
      EMBASE, and the strength of evidence was classified using the Centre for Evidence
      Based Medicine classification schema. Probiotics for VLBW neonates may decrease
      the incidence of NEC. Providers may choose to give probiotics to VLBW neonates at
      risk of acquiring NEC in facilities with a high NEC incidence. Clinicians must
      monitor infants for possible adverse effects. Contraindications for probiotic use
      include extremely low birth weight, clinical instability, abnormal abdominal
      examination, the presence of congenital abnormalities, post-NEC, stage III
      asphyxia, and umbilical catheters. 

PMID- 24675628
TI  - Sturge-Weber syndrome: a case study.
AB  - Sturge-Weber syndrome (SWS) is a rare, congenital neurocutaneous condition
      (affecting both the skin and the brain) characterized by a facial port-wine stain
      located specifically on the ophthalmic branch of the trigeminal nerve, cerebral
      vascular abnormalities, and potential eye involvement. The incidence of SWS is
      approximately 1 in 20,000 to 50,000 infants, and therefore all clinical
      presentations are important to discuss. This article describes a case
      presentation of SWS and then discusses the etiology, pathophysiology, management,
      diagnosis, and prognosis of SWS. 

PMID- 24675629
TI  - Construction of a reusable, high-fidelity model to enhance extracorporeal
      membrane oxygenation training through simulation.
AB  - Initiation of extracorporeal membrane oxygenation (ECMO) is stressful, especially
      for inexperienced extracorporeal life support providers. The main objective of
      this study was to create a novel, reusable mannequin for high-fidelity simulation
      of ECMO initiation. We modified a Laerdal neonatal mannequin (SimNewB; Stavanger,
      Norway) so that it could be used to simulate an ECMO initiation. A simulation of
      a neonatal patient suffering from meconium aspiration was performed in the
      pediatric intensive care unit, and participants included new extracorporeal life
      support specialists in addition to the composition of the clinical ECMO team. A
      total of 17 individuals participated in the neonatal ECMO initiation simulation.
      Questionnaire results showed that 88% of participants felt better prepared to
      assist in an ECMO initiation after the simulation. All participants (100%) agreed
      that the modified mannequin and the environment were realistic and that this
      simulation helps teamwork and communication in future initiations of ECMO.
      Simulation can be used for the prevention, identification, and reduction of
      anxiety-related crisis situations that novice providers may infrequently
      encounter during routine clinical use of mechanical circulatory support. Use of a
      reusable, high-fidelity mannequin may be beneficial for effective team training
      of complex pediatric ECMO-related procedures. 

PMID- 24675630
TI  - Lay press material on preterm birth: no real progress in education on potentially
      problematic outcomes.
AB  - Premature birth has many implications for the newborn, parents, other family
      members, and the healthcare system. Ten years ago, a literature search was
      executed through US newspapers, magazines, and news wires over a 6-month period
      to determine the scope of lay media coverage concerning premature birth outcomes.
      The results indicated that lay media resources provided limited information on
      the topic. In May 2013, the original search was replicated in an effort to
      determine whether the current scope of coverage had expanded since the original
      search was conducted. This article discusses the results of the May 2013
      literature search of lay media resources for information on premature birth and
      its potential outcomes. 

PMID- 24675631
TI  - Moderate hypothermia: is selective head cooling or whole body cooling better?

PMID- 24675632
TI  - Screening for critical congenital heart disease in newborns using pulse oximetry:
      evaluation of nurses' knowledge and adherence.
AB  - PURPOSE: The purpose of this project was to evaluate the benefits of an online
      nursing education program addressing the significance and rationale of an
      evidence-based critical congenital heart disease (CCHD) screening protocol using
      pulse oximetry implemented on full-term newborns delivered at an academic
      obstetric referral center. The aim was to assess nurses' knowledge of the
      protocol and nurses' adherence to the protocol documentation before and after the
      education module was implemented. SUBJECTS: Registered nurses working in the
      birthing center who completed the online knowledge tests and an education module.
      DESIGN: A repeated-measures quality improvement study was conducted to assess
      nurses' knowledge of the evidence supporting CCHD screening by pulse oximetry and
      adherence to the correct documentation of the screening protocol before,
      immediately after, and 3 months following participation in an online education
      module. METHODS: Nurses' knowledge of the CCHD screening protocol was determined
      by the number of correct answers on a 10-item online test administered before and
      after the education module. Adherence to correct documentation of the protocol
      before and after the education intervention was evaluated. The medical charts of
      300 newborns delivered at the center with pulse oximetry readings performed after
      24 hours of age and before discharge were randomly selected and reviewed.
      RESULTS: A significant improvement in knowledge test scores was observed
      immediately after the education module (9.1 +/- 1.0), relative to baseline (8.4
      +/- 1.2; paired t = 3.02, P = .0046). A significant increase in knowledge test
      scores measured at baseline, immediately after, and 3 months postintervention was
      also indicated (F = 3.25; df = 2, 24; P = .0564). Documentation of the protocol
      in the medical charts for the location of the readings significantly improved
      after the educational intervention (right hand: 28%, 83%, and 90%; right foot:
      27%, 82%, and 89%; both P < .0001). CONCLUSIONS: Providing education to staff
      before implementing new practice changes enhances their knowledge. Quality
      improvement monitoring is recommended to ensure nursing adherence to any practice
      change.

PMID- 24675633
TI  - Improvements in staff quality of work life and family satisfaction following the
      move to single-family room NICU design.
AB  - OBJECTIVE: The purpose of this study was to determine whether there were
      differences in staff quality of work life and parent satisfaction when a neonatal
      intensive care unit moved from an open-bay design to a single-room model of care.
      DESIGN: This descriptive study measured staff quality of work life and family
      satisfaction before and at 2 time periods after the relocation of a perinatal
      centre and the introduction of single-family room care. Differences in work life
      quality and satisfaction were determined using 2-sample t-tests. RESULT: There
      were improvements in staff quality of work life and family satisfaction at both
      time periods following the move. CONCLUSION: Lessons learned may be of value to
      other units considering such a move. A neonatal intensive care unit designed to
      contribute to parental and staff well-being is a model to be considered for
      future neonatal designs.

PMID- 24675635
TI  - Photodynamic inactivation of mold fungi spores by newly developed charged
      corroles.
AB  - The photodynamic effect, originally used in photodynamic therapy (PDT) for the
      treatment of different diseases, e.g. of cancer, has recently been introduced for
      the inactivation of bacteria. Mold fungi, which provoke health problems like
      allergies and diseases of the respiratory tract, are even more resistant and
      their biology is also very different. This study presents the development of four
      new photosensitizers, which, in combination with low doses of white light,
      inhibit the germination of mold fungi spores. Two of them even cause lethal
      damage to the conidia (spores) which are responsible for the spreading of mold
      fungi. The photoactivity of the newly synthesized corroles was obtained by their
      application on three different mold fungi: Aspergillus niger, Cladosporium
      cladosporoides, and Penicillium purpurgenum. To distinguish between inactivation
      of germination and permanent damage, the fungi were first incubated under
      illumination for examination of photosensitizer-induced growth inhibition and
      then left in darkness to test the survival of the conidia. None of the compounds
      displayed dark toxicity, but all of them attenuated or prevented germination when
      exposed to light, and the positively charged complexes induced a complete damage
      of the conidia. 

PMID- 24675634
TI  - Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder:
      evidence for pleiotropy.
AB  - In the U.S.A., cocaine is the second most abused illicit drug. Variants within
      the CHRNB3-A6 gene cluster have been associated with cigarette consumption in
      several GWAS. These receptors represent intriguing candidates for the study of
      cocaine dependence because nicotinic receptors are thought to be involved in
      generalized addiction pathways. Using genotypic data from a GWAS of the Study of
      Addiction: Genetics and Environment (SAGE) dataset, we tested for association of
      CHRNB3-A6 SNPs with DSM-5 cocaine use disorder. Multiple SNPs in the region were
      significantly associated with increased risk of cocaine use disorder. Inclusion
      of the most significant SNP as a covariate in a linear regression model provided
      evidence for an additional independent signal within this locus for cocaine use
      disorder. These results suggest that the CHRNB3-A6 locus contains multiple
      variants affecting risk for vulnerability to cocaine and nicotine dependence as
      well as bipolar disorder, suggesting that they have pleiotropic effects. 

PMID- 24675636
TI  - Discovering aptamers by cell-SELEX against human soluble growth factors
      ectopically expressed on yeast cell surface.
AB  - SELEX, the process of selecting aptamers, is often hampered by the difficulty of
      preparing target molecules in their native forms and by a lack of a simple yet
      quantitative assay for monitoring enrichment and affinity of reactive aptamers.
      In this study, we sought to discover DNA aptamers against human serum markers for
      potential therapeutic and diagnostic applications. To circumvent soluble
      expression and immobilization for performing SELEX, we ectopically expressed
      soluble growth factors on the surface of yeast cells to enable cell-SELEX and
      devised a flow cytometry-based method to quantitatively monitor progressive
      enrichment of specific aptamers. High-throughput sequencing of selected pools
      revealed that the emergence of highly enriched sequences concurred with the
      increase in the percentage of reactive aptamers shown by flow cytometry.
      Particularly, selected DNA aptamers against VEGF were specific and of high
      affinity (K(D)  = ~ 1 nM) and demonstrated a potent inhibition of capillary tube
      formation of endothelial cells, comparable to the effect of a clinically approved
      anti-VEGF antibody drug, bevacizumab. Considering the fact that many mammalian
      secretory proteins have been functionally expressed in yeast, the strategy of
      implementing cell-SELEX and quantitative binding assay can be extended to
      discover aptamers against a broad array of soluble antigens.

PMID- 24675637
TI  - An integrated model of multiple-condition ChIP-Seq data reveals predeterminants
      of Cdx2 binding.
AB  - Regulatory proteins can bind to different sets of genomic targets in various cell
      types or conditions. To reliably characterize such condition-specific regulatory
      binding we introduce MultiGPS, an integrated machine learning approach for the
      analysis of multiple related ChIP-seq experiments. MultiGPS is based on a
      generalized Expectation Maximization framework that shares information across
      multiple experiments for binding event discovery. We demonstrate that our
      framework enables the simultaneous modeling of sparse condition-specific binding
      changes, sequence dependence, and replicate-specific noise sources. MultiGPS
      encourages consistency in reported binding event locations across multiple
      condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment
      levels at each event. MultiGPS's multi-experiment modeling approach thus provides
      a reliable platform for detecting differential binding enrichment across
      experimental conditions. We demonstrate the advantages of MultiGPS with an
      analysis of Cdx2 binding in three distinct developmental contexts. By accurately
      characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight
      into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition
      specific Cdx2 sites characterized by MultiGPS are highly associated with pre
      existing genomic context, suggesting that such sites are pre-determined by cell
      specific regulatory architecture. However, MultiGPS-defined condition-independent
      sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2
      can bind to a subset of locations regardless of genomic environment. A summary of
      this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5. 

PMID- 24675642
TI  - Clinically-important brain injury and CT findings in pediatric mild traumatic
      brain injuries: a prospective study in a Chinese reference hospital.
AB  - This study investigated injury patterns and the use of computed tomography (CT)
      among Chinese children with mild traumatic brain injury (MTBI). We enrolled
      children with MTBI who were treated within 24 hours of head trauma in the
      emergency department of Wuhan Medical Care Center for Women and Children in
      Wuhan, China. Characteristics of MTBIs were analyzed by age and gender. Results
      of cranial CT scan and clinically-important brain injury (ciTBI) for children
      were obtained. The definition of ciTBI was: death from TBI, intubation for more
      than 24 h for TBI, neurosurgery, or hospital admission of 2 nights or more. Of
      455 eligible patients with MTBI, ciTBI occurred in two, and no one underwent
      neurosurgical intervention. CT scans were performed for 441 TBI patients (96.9%),
      and abnormal findings were reported for 147 patients (33.3%, 95% CI 29.0-37.8).
      Falls were the leading cause of MTBI (61.5%), followed by blows (18.9%) and
      traffic collisions (14.1%) for children in the 0-2 group and 10-14 group. For
      children aged between 3 and 9, the top three causes of TBI were falls, traffic
      collisions and blows. Leisure activity was the most reported activity when
      injuries occurred for all age groups. Sleeping/resting and walking ranked in the
      second and third place for children between 0 and 2 years of age, and walking and
      riding for the other two groups. The places where the majority injuries occurred
      were the home for the 0-2 and 3-9 years of age groups, and school for the 10-14
      years of age group. There was no statistical difference between boys and girls
      with regard to the activity that caused the MTBI. This study highlights the
      important roles that parents and school administrators in the development of
      preventive measures to reduce the risk of traumatic brain injury in children.
      Also, identifying children who had a head trauma at very low risk of clinically
      important TBI for whom CT might be unnecessary is a priority area of research in
      China. 

PMID- 24675643
TI  - Water quality assessment in the Harbin reach of the Songhuajiang River (China)
      based on a fuzzy rough set and an attribute recognition theoretical model.
AB  - A large number of parameters are acquired during practical water quality
      monitoring. If all the parameters are used in water quality assessment, the
      computational complexity will definitely increase. In order to reduce the input
      space dimensions, a fuzzy rough set was introduced to perform attribute
      reduction. Then, an attribute recognition theoretical model and entropy method
      were combined to assess water quality in the Harbin reach of the Songhuajiang
      River in China. A dataset consisting of ten parameters was collected from January
      to October in 2012. Fuzzy rough set was applied to reduce the ten parameters to
      four parameters: BOD5, NH3-N, TP, and F. coli (Reduct A). Considering that DO is
      a usual parameter in water quality assessment, another reduct, including DO,
      BOD5, NH3-N, TP, TN, F, and F. coli (Reduct B), was obtained. The assessment
      results of Reduct B show a good consistency with those of Reduct A, and this
      means that DO is not always necessary to assess water quality. The results with
      attribute reduction are not exactly the same as those without attribute
      reduction, which can be attributed to the alpha value decided by subjective
      experience. The assessment results gained by the fuzzy rough set obviously reduce
      computational complexity, and are acceptable and reliable. The model proposed in
      this paper enhances the water quality assessment system. 

PMID- 24675644
TI  - Symmetry-protected surface state on Mo(1 1 2).
AB  - We report the experimental identification of a symmetry-protected surface state
      on Mo(1 1 2). The utilization of photon-energy- and polarization-dependent angle
      resolved photoemission spectroscopy clearly demonstrates that this true surface
      state preserves its two-dimensional character despite the fact that it resides
      within the projection of the bulk bands along the Gamma-X line of the surface
      Brillouin zone. This surface state on Mo(1 1 2) exists due to the forbidden
      hybridization between the bulk and the surface states, each of which possesses
      different state symmetries within the crystal. The experimental identification of
      such a surface state possibly opens up pathways towards controlled manipulation
      between true surface states and the surface resonances (i.e. between two
      dimensional and quasi-two-dimensional states) by breaking the symmetry of the
      crystal surface.

PMID- 24675645
TI  - Functional ultrasound imaging reveals different odor-evoked patterns of vascular
      activity in the main olfactory bulb and the anterior piriform cortex.
AB  - Topographic representation of the outside world is a key feature of sensory
      systems, but so far it has been difficult to define how the activity pattern of
      the olfactory information is distributed at successive stages in the olfactory
      system. We studied odor-evoked activation patterns in the main olfactory bulb and
      the anterior piriform cortex of rats using functional ultrasound (fUS) imaging.
      fUS imaging is based on the use of ultrafast ultrasound scanners and detects
      variations in the local blood volume during brain activation. It makes deep brain
      imaging of ventral structures, such as the piriform cortex, possible. Stimulation
      with two different odors (hexanal and pentylacetate) induced the activation of
      odor-specific zones that were spatially segregated in the main olfactory bulb.
      Interestingly, the same odorants triggered the activation of the entire anterior
      piriform cortex, in all layers, with no distinguishable odor-specific areas
      detected in the power Doppler images. These fUS imaging results confirm the
      spatial distribution of odor-evoked activity in the main olfactory bulb, and
      furthermore, they reveal the absence of such a distribution in the anterior
      piriform cortex at the macroscopic scale in vivo. 

PMID- 24675646
TI  - Complex relationship between BOLD-fMRI and electrophysiological signals in
      different olfactory bulb layers.
AB  - Blood oxygenation level dependent functional magnetic resonance imaging (BOLD
      fMRI), one of the most powerful technologies in neuroscience, measures neural
      activity indirectly. Therefore, systematic correlation of BOLD signals with other
      neural activity measurements is critical to understanding and then using the
      technology. Numerous studies have revealed that the BOLD signal is determined by
      many factors and is better correlated with local field potentials (LFP) than
      single/multiple unit firing. The relationship between BOLD and LFP signals under
      higher spatial resolution is complex and remains unclear. Here, changes of BOLD
      and LFP signals in the glomerular (GL), mitral cell (MCL), and granular cell
      layers (GCL) of the olfactory bulb were evoked by odor stimulation and
      sequentially acquired using high-resolution fMRI and electrode array. The
      experimental results revealed a rather complex relationship between BOLD and LFP
      signals. Both signal modalities were increased layer-dependently by odor
      stimulation, but the orders of signal intensity were significantly different:
      GL>MCL>GCL and GCL>GL>MCL for BOLD and LFP, respectively. During odor
      stimulation, the temporal features of LFPs were similar for a given band in
      different layers, but different for different frequency bands in a given layer.
      The BOLD and LFP signals in the low gamma frequency band correlated the best.
      This study provides new evidence for the consistency between structure and
      function in understanding the neurophysiological basis of BOLD signals, but also
      reminds that caution must be taken in interpreting of BOLD signals in regard to
      neural activity. 

PMID- 24675647
TI  - The functional oculomotor network and saccadic cognitive control in healthy
      elders.
AB  - Decline in executive function is the most common age-associated cognitive deficit
      and may be a risk factor for neurodegenerative disease. The antisaccade (AS) task
      involves inhibition of a prepotent visuomotor response and is a well-validated
      executive function test in aging and neurodegeneration. We investigated the
      functional connectivity of the cortical oculomotor network during successful AS
      performance in healthy elders. Elevated BOLD activity in the right lateral
      frontal eye field (rlatFEF), a region linked to volume loss in individuals with
      impaired AS performance, was associated with worse AS performance and weaker
      network efficiency. In contrast, hub integrity of the right dorsolateral
      prefrontal cortex (rDLPFC) and anterior cingulate cortex (rACC) was associated
      with better AS performance. These data suggest that while several right lateral
      frontal regions are central nodes in the oculomotor network, the rlatFEF
      demonstrates early neural aberrations and the rDLPFC and rACC continue to support
      inhibitory cognitive control in healthy elders. We conclude that alterations in
      AS task functional connectivity, quantified as hub and network efficiency, may be
      clinically-relevant biomarkers of cognitive decline in executive functioning. 

PMID- 24675648
TI  - The effect of echo time and post-processing procedure on blood oxygenation level
      dependent (BOLD) functional connectivity analysis.
AB  - While spontaneous BOLD fMRI signal is a common tool to map functional
      connectivity, unexplained inter- and intra-subject variability frequently
      complicates interpretation. Similar to evoked BOLD fMRI responses, spontaneous
      BOLD signal is expected to vary with echo time (TE) and corresponding
      intra/extravascular sensitivity. This may contribute to discrepant conclusions
      even following identical post-processing pipelines. Here we applied commonly
      utilized independent component analysis (ICA) as well as seed-based correlation
      analysis and investigated default mode network (DMN) and visual network (VN)
      detection from BOLD data acquired at three TEs (3T; TR=2500ms; TE=15ms, 35ms, and
      55ms) and from quantitative R2* maps. Explained variance in ICA analysis was
      significantly higher (P<0.05) when R2*-derived maps were considered relative to
      single-TE data with no post-processing. While explained variance in the BOLD data
      increased with motion correction, R2* derived DMN and VN were minimally affected
      by motion correction. Explained variance increased in all data when physiological
      noise confounds were removed using CompCor. Notably, the R2*-derived connectivity
      patterns were least affected by motion and physiological noise confounds in a
      seed-based correlation analysis. Intermediate (35ms) and long (55ms) TE data
      provided similar spatial and temporal characteristics only after reducing motion
      and physiological noise contamination. Results provide an exemplar for how 3T
      spontaneous BOLD network detection varies with TE and post-processing procedure
      over the range of commonly acquired TE values. 

PMID- 24675650
TI  - Differential nitrogen cycling in semiarid sub-shrubs with contrasting leaf habit.
AB  - Nitrogen (N) is, after water, the most limiting resource in semiarid ecosystems.
      However, knowledge on the N cycling ability of semiarid woody plants is still
      very rudimentary. This study analyzed the seasonal change in the N concentrations
      and pools of the leaves and woody organs of two species of semiarid sub-shrubs
      with contrasting leaf habit. The ability of both species to uptake, remobilize
      and recycle N, plus the main storage organ for N during summer drought were
      evaluated. We combined an observational approach in the field with experimental
      (15)N labelling of adult individuals grown in sand culture. Seasonal patterns of
      N concentrations were different between species and organs and foliar N
      concentrations of the summer deciduous Lepidium subulatum were almost double
      those of the evergreen Linum suffruticosum. L. subulatum up took ca. 60% more
      external N than the evergreen and it also had a higher N resorption efficiency
      and proficiency. Contrastingly, L. suffruticosum relied more on internal N
      remobilization for shoot growth. Differently to temperate species, the evergreen
      stored N preferentially in the main stem and old trunks, while the summer
      deciduous stored it in the foliage and young stems. The higher ability of L.
      subulatum to uptake external N can be related to its ability to perform
      opportunistic growth and exploit the sporadic pulses of N typical of semiarid
      ecosystems. Such ability may also explain its high foliar N concentrations and
      its preferential storage of N in leaves and young stems. Finally, L.
      suffruticosum had a lower ability to recycle N during leaf senescence. These
      strategies contrast with those of evergreen and deciduous species from temperate
      and boreal areas, highlighting the need of further studies on semiarid and arid
      plants.

PMID- 24675649
TI  - Interplay between functional connectivity and scale-free dynamics in intrinsic
      fMRI networks.
AB  - Studies employing functional connectivity-type analyses have established that
      spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signals
      are organized within large-scale brain networks. Meanwhile, fMRI signals have
      been shown to exhibit 1/f-type power spectra - a hallmark of scale-free dynamics.
      We studied the interplay between functional connectivity and scale-free dynamics
      in fMRI signals, utilizing the fractal connectivity framework - a multivariate
      extension of the univariate fractional Gaussian noise model, which relies on a
      wavelet formulation for robust parameter estimation. We applied this framework to
      fMRI data acquired from healthy young adults at rest and while performing a
      visual detection task. First, we found that scale-invariance existed beyond
      univariate dynamics, being present also in bivariate cross-temporal dynamics.
      Second, we observed that frequencies within the scale-free range do not
      contribute evenly to inter-regional connectivity, with a systematically stronger
      contribution of the lowest frequencies, both at rest and during task. Third, in
      addition to a decrease of the Hurst exponent and inter-regional correlations,
      task performance modified cross-temporal dynamics, inducing a larger contribution
      of the highest frequencies within the scale-free range to global correlation.
      Lastly, we found that across individuals, a weaker task modulation of the
      frequency contribution to inter-regional connectivity was associated with better
      task performance manifesting as shorter and less variable reaction times. These
      findings bring together two related fields that have hitherto been studied
      separately - resting-state networks and scale-free dynamics, and show that scale
      free dynamics of human brain activity manifest in cross-regional interactions as
      well. 

PMID- 24675654
TI  - Treatment sequencing in metastatic castrate-resistant prostate cancer.
AB  - Six different treatments have demonstrated improved survival in phase III trials
      targeted to patients with metastatic castration-resistant prostate cancer
      (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel
      T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel,
      abiraterone, enzalutamide and radium-223. Despite much progress in recent years,
      much is yet unknown and debates occur over optimal treatment choices and
      sequences. None of the new agents have been compared to one another, thus
      physicians in practice today must make choices based on non-randomized
      comparisons, toxicity considerations and various assumptions. Abiraterone is now
      moving into the front line mCRPC space given recent regulatory approvals and
      enzalutamide will follow soon. Both of the hormonal agents have less toxicity
      when compared to chemotherapeutic options and both of these hormonal agents are
      expected to be used in a considerable number of mCRPC patients in the years
      ahead. Little data are available for the post-abiraterone or post-enzalutamide
      setting. In this review the currently available sequencing data are summarized
      and interpreted. It is now clear that cross resistance is a potential issue
      between various treatments, especially those agents that target the androgen
      axis. This review highlights the need for additional studies to optimize the
      current treatments for these patients. 

PMID- 24675655
TI  - Lycopene and male infertility.
AB  - Excessive amounts of reactive oxygen species (ROS) cause a state of oxidative
      stress, which result in sperm membrane lipid peroxidation, DNA damage and
      apoptosis, leading to decreased sperm viability and motility. Elevated levels of
      ROS are a major cause of idiopathic male factor infertility, which is an
      increasingly common problem today. Lycopene, the most potent singlet oxygen
      quencher of all carotenoids, is a possible treatment option for male infertility
      because of its antioxidant properties. By reacting with and neutralizing free
      radicals, lycopene could reduce the incidence of oxidative stress and thus,
      lessen the damage that would otherwise be inflicted on spermatozoa. It is
      postulated that lycopene may have other beneficial effects via nonoxidative
      mechanisms in the testis, such as gap junction communication, modulation of gene
      expression, regulation of the cell cycle and immunoenhancement. Various lycopene
      supplementation studies conducted on both humans and animals have shown promising
      results in alleviating male infertility-lipid peroxidation and DNA damage were
      decreased, while sperm count and viability, and general immunity were increased.
      Improvement of these parameters indicates a reduction in oxidative stress, and
      thus the spermatozoa is less vulnerable to oxidative damage, which increases the
      chances of a normal sperm fertilizing the egg. Human trials have reported
      improvement in sperm parameters and pregnancy rates with supplementation of 4-8
      mg of lycopene daily for 3-12 months. However, further detailed and extensive
      research is still required to determine the dosage and the usefulness of lycopene
      as a treatment for male infertility. 

PMID- 24675656
TI  - Serologic prevalence of Toxoplasma gondii in Indian women of child bearing age
      and effects of social and environmental factors.
AB  - BACKGROUND: Seroprevalence and incidence of toxoplasmosis in women of child
      bearing age has remained a contentious issue in the Indian subcontinent.
      Different laboratories have used different patient recruitment criteria, methods
      and variable results, making these data difficult to compare. AIM: To map the
      point-prevalence and incidence of toxoplasmosis in India. MATERIAL AND METHODS:
      In this cross-sectional study, a total of 1464 women of fertile age were
      recruited from 4 regions using similar recruitment plans. This included women
      from northern (203), southern (512), eastern (250) and western (501) regions of
      India. All samples were transported to a central laboratory in Delhi and tested
      using VIDAS technology. Their age, parity, eating habits and other demographic
      and clinical details were noted. RESULTS: Most women were in the 18-25 years age
      group (48.3%), followed by 26-30 years (28.2%) and 31-35 years (13.66). Few (45)
      women older than 35 yr. were included. Overall prevalence of anti-Toxoplasma IgG
      antibodies was seen in 22.40%, with significantly more in married women (25.8%)
      as compared to single women (4.3%). Prevalence increased steadily with age: 18.1%
      in the 18-25 yr. age group to 40.5% in women older than 40 yr. The prevalence was
      high (66%) in those who resided in mud houses. Region-wise, the highest
      prevalence was observed in South India (37.3%) and the lowest (8.8%) in West
      Indian women. This difference was highly significant (P<0.001). Prevalence was
      21.2% in East India and 19.7% in North India. The IgM positivity rate ranged from
      0.4% to 2.9% in four study centers. CONCLUSIONS: This pan-India study shows a
      prevalence rate of 22.4% with a wide variation in four geographical regions
      ranging from as low as 8.8% to as high as 37.3%. The overall IgM positivity rate
      was 1.43%, indicating that an estimated 56,737-176,882 children per year are born
      in India with a possible risk of congenital toxoplasmosis.

PMID- 24675657
TI  - Differences in vascular nitric oxide and endothelium-derived hyperpolarizing
      factor bioavailability in blacks and whites.
AB  - OBJECTIVE: Abnormalities in nitric oxide (NO) bioavailability have been reported
      in blacks. Whether there are differences in endothelium-derived hyperpolarizing
      factor (EDHF) in addition to NO between blacks and whites and how these affect
      physiological vasodilation remain unknown. We hypothesized that the
      bioavailability of vascular NO and EDHF, at rest and with pharmacological and
      physiological vasodilation, varies between whites and blacks. APPROACH AND
      RESULTS: In 74 white and 86 black subjects without known cardiovascular disease
      risk factors, forearm blood flow was measured using plethysmography at rest and
      during inhibition of NO with N(G)-monomethyl-L-arginine and of K(+) Ca channels
      (EDHF) with tetraethylammonium. The reduction in resting forearm blood flow was
      greater with N(G)-monomethyl-L-arginine (P=0.019) and similar with
      tetraethylammonium in whites compared with blacks. Vasodilation with bradykinin,
      acetylcholine, and sodium nitroprusside was lower in blacks compared with whites
      (all P<0.0001). Inhibition with N(G)-monomethyl-L-arginine was greater in whites
      compared with blacks with bradykinin, acetylcholine, and exercise. Inhibition
      with tetraethylammonium was lower in blacks with bradykinin, but greater during
      exercise and with acetylcholine. CONCLUSIONS: The contribution to both resting
      and stimulus-mediated vasodilator tone of NO is greater in whites compared with
      blacks. EDHF partly compensates for the reduced NO release in exercise and
      acetylcholine-mediated vasodilation in blacks. Preserved EDHF but reduced NO
      bioavailability and sensitivity characterizes the vasculature in healthy blacks.
      CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov/. Unique identifier:
      NCT00166166.

PMID- 24675658
TI  - Supporting roles of platelet thrombospondin-1 and CD36 in thrombus formation on
      collagen.
AB  - OBJECTIVE: Platelets abundantly express the membrane receptor CD36 and store its
      ligand thrombospondin-1 (TSP1) in the alpha-granules. We investigated whether
      released TSP1 can support platelet adhesion and thrombus formation via
      interaction with CD36. APPROACH AND RESULTS: Mouse platelets deficient in CD36
      showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression.
      Deficiency in either CD36 or TSP1 resulted in markedly increased dissolution of
      thrombi formed on collagen, although thrombus buildup was unchanged. In
      mesenteric vessels in vivo, deficiency in CD36 prolonged the time to occlusion
      and enhanced embolization, which was in agreement with earlier observations in
      TSP1-deficient mice. Thrombi formed using wild-type blood stained positively for
      secreted TSP1. Releasate from wild-type but not from TSP1-deficient platelets
      enhanced platelet activation, phosphatidylserine expression, and thrombus
      formation on collagen. The enhancement was dependent on CD36 because it was
      without effect on thrombus formation by CD36-deficient platelets. CONCLUSIONS:
      These results demonstrate an anchoring role of platelet-released TSP1 via CD36 in
      platelet adhesion and collagen-dependent thrombus stabilization. Thus, the TSP1
      CD36 tandem is another platelet ligand-receptor axis contributing to the
      maintenance of a stable thrombus.

PMID- 24675660
TI  - Diabetes mellitus and ischemic diseases: molecular mechanisms of vascular repair
      dysfunction.
AB  - In patients with diabetes mellitus, the ability of ischemic tissue to synchronize
      the molecular and cellular events leading to restoration of tissue perfusion in
      response to the atherosclerotic occlusion of a patent artery is markedly
      impaired. As a consequence, adverse tissue remodeling and the extent of ischemic
      injury are intensified, leading to increased morbidity and mortality. Growing
      evidence from preclinical and clinical studies has implicated alterations in
      hypoxia-inducible factor 1 levels in the abrogation of proangiogenic pathways,
      including vascular endothelial growth factor A/phosphoinositide 3'
      kinase/AKT/endothelial nitric oxide synthase and in the activation of
      antiangiogenic signals characterized by accumulation of advanced glycation end
      products, reactive oxygen species overproduction, and endoplasmic reticulum
      stress. In addition, the diabetic milieu shows a switch toward proinflammatory
      antiregenerative pathways. Finally, the mobilization, subsequent recruitment, and
      the proangiogenic potential of the different subsets of angiogenesis-promoting
      bone marrow-derived cells are markedly impaired in the diabetic environment. In
      this review, we will give an overview of the current understanding on the
      signaling molecules contributing to the diabetes mellitus-induced impairment of
      postischemic revascularization mainly in the setting of myocardial infarction or
      critical limb ischemia.

PMID- 24675659
TI  - Comparative genome-wide association studies in mice and humans for trimethylamine
      N-oxide, a proatherogenic metabolite of choline and L-carnitine.
AB  - OBJECTIVE: Elevated levels of plasma trimethylamine N-oxide (TMAO), the product
      of gut microbiome and hepatic-mediated metabolism of dietary choline and L
      carnitine, have recently been identified as a novel risk factor for the
      development of atherosclerosis in mice and humans. The goal of this study was to
      identify the genetic factors associated with plasma TMAO levels. APPROACH AND
      RESULTS: We used comparative genome-wide association study approaches to discover
      loci for plasma TMAO levels in mice and humans. A genome-wide association study
      in the hybrid mouse diversity panel identified a locus for TMAO levels on
      chromosome 3 (P=2.37 * 10(-6)) that colocalized with a highly significant (P=1.07
      * 10(-20)) cis-expression quantitative trait locus for solute carrier family 30
      member 7. This zinc transporter could thus represent 1 positional candidate gene
      responsible for the association signal at this locus in mice. A genome-wide
      association study for plasma TMAO levels in 1973 humans identified 2 loci with
      suggestive evidence of association (P=3.0 * 10(-7)) on chromosomes 1q23.3 and
      2p12. However, genotyping of the lead variants at these loci in 1892 additional
      subjects failed to replicate their association with plasma TMAO levels.
      CONCLUSIONS: The results of these limited observational studies indicate that, at
      least in humans, genes play a marginal role in determining TMAO levels and that
      any genetic effects are relatively weak and complex. Variation in diet or the
      repertoire of gut microbiota may be more important determinants of plasma TMAO
      levels in mice and humans, which should be investigated in future studies.

PMID- 24675661
TI  - Nicotinic acid activates the capsaicin receptor TRPV1: Potential mechanism for
      cutaneous flushing.
AB  - OBJECTIVE: Nicotinic acid (also known as niacin or vitamin B3), widely used to
      treat dyslipidemias, represents an effective and safe means to reduce the risk of
      mortality from cardiovascular disease. Nonetheless, a substantial fraction of
      patients discontinue treatment because of a strong side effect of cutaneous
      vasodilation, commonly termed flushing. In the present study, we tested the
      hypothesis that nicotinic acid causes flushing partially by activating the
      capsaicin receptor TRPV1, a polymodal cellular sensor that mediates the flushing
      response on consumption of spicy food. APPROACH AND RESULTS: We observed that the
      nicotinic acid-induced increase in blood flow was substantially reduced in Trpv1(
      /-) knockout mice, indicating involvement of the channel in flushing response.
      Using exogenously expressed TRPV1, we confirmed that nicotinic acid at
      submillimolar to millimolar concentrations directly and potently activates TRPV1
      from the intracellular side. Binding of nicotinic acid to TRPV1 lowers its
      activation threshold for heat, causing channel opening at physiological
      temperatures. The activation of TRPV1 by voltage or ligands (capsaicin and 2
      aminoethoxydiphenyl borate) is also potentiated by nicotinic acid. We further
      demonstrated that nicotinic acid does not compete directly with capsaicin but may
      activate TRPV1 through the 2-aminoethoxydiphenyl borate activation pathway. Using
      live-cell fluorescence imaging, we observed that nicotinic acid can quickly enter
      the cell through a transporter-mediated pathway to activate TRPV1. CONCLUSIONS:
      Direct activation of TRPV1 by nicotinic acid may lead to cutaneous vasodilation
      that contributes to flushing, suggesting a potential novel pathway to inhibit
      flushing and to improve compliance.

PMID- 24675662
TI  - Coenzyme Q10 promotes macrophage cholesterol efflux by regulation of the
      activator protein-1/miR-378/ATP-binding cassette transporter G1-signaling
      pathway.
AB  - OBJECTIVE: Recent studies have shown the role of miRNAs in macrophage reverse
      cholesterol transport and atherogenesis. We hypothesized that coenzyme Q10
      (CoQ10) may increase macrophage reverse cholesterol transport by regulating miRNA
      expression that contributes to the prevention of atherosclerosis. APPROACH AND
      RESULTS: CoQ10 treatment suppressed oxidized low-density lipoprotein-induced
      macrophage foam cell formation by ameliorating the binding of activator protein-1
      to the putative promoter region of miR-378 primary transcript, thus decreasing
      the miR-378 level and enhancing the ATP-binding cassette transporter G1-mediated
      macrophage cholesterol efflux to high-density lipoprotein. Subsequently, the axis
      of activator protein-1/miR-378/ATP-binding cassette transporter G1 cholesterol
      efflux was confirmed in peritoneal macrophages isolated from CoQ10-treated
      apolipoprotein E-deficient mice. Finally, CoQ10 consumption promoted macrophage
      reverse cholesterol transport and inhibited the progression of atherosclerosis in
      apolipoprotein E-deficient mice. CONCLUSIONS: This study identified activator
      protein-1/miR-378/ATP-binding cassette transporter G1 as a novel cascade for
      CoQ10 in facilitating macrophage cholesterol efflux in vitro and in vivo. Our
      data thus imply that both CoQ10 and miR-378 are promising candidates for
      atherosclerosis prevention and treatment.

PMID- 24675663
TI  - Crucial role of rho-kinase in pressure overload-induced right ventricular
      hypertrophy and dysfunction in mice.
AB  - OBJECTIVE: Right ventricular (RV) failure is the leading cause of death in
      various cardiopulmonary diseases, including pulmonary hypertension. It is
      generally considered that the RV is vulnerable to pressure overload as compared
      with the left ventricle (LV). However, as compared with LV failure, the molecular
      mechanisms of RV failure are poorly understood, and hence therapeutic targets of
      the disorder remain to be elucidated. Thus, we aimed to identify molecular
      therapeutic targets for RV failure in a mouse model of pressure overload.
      APPROACH AND RESULTS: To induce pressure overload to respective ventricles, we
      performed pulmonary artery constriction or transverse aortic constriction in
      mice. We first performed microarray analysis and found that the molecules related
      to RhoA/Rho-kinase and integrin pathways were significantly upregulated in the RV
      with pulmonary artery constriction compared with the LV with transverse aortic
      constriction. Then, we examined the responses of both ventricles to chronic
      pressure overload in vivo. We demonstrated that compared with transverse aortic
      constriction, pulmonary artery constriction caused greater extents of mortality,
      Rho-kinase expression (especially ROCK2 isoform), and oxidative stress in
      pressure-overloaded RV, reflecting the weakness of the RV in response to pressure
      overload. Furthermore, mice with myocardial-specific overexpression of dominant
      negative Rho-kinase showed resistance to pressure overload-induced hypertrophy
      and dysfunction associated with reduced oxidative stress. Finally, dominant
      negative Rho-kinase mice showed a significantly improved long-term survival in
      both pulmonary artery constriction and transverse aortic constriction as compared
      with littermate controls. CONCLUSION: These results indicate that the Rho-kinase
      pathway plays a crucial role in RV hypertrophy and dysfunction, suggesting that
      the pathway is a novel therapeutic target of RV failure in humans.

PMID- 24675664
TI  - Disseminated arterial calcification and enhanced myogenic response are associated
      with abcc6 deficiency in a mouse model of pseudoxanthoma elasticum.
AB  - OBJECTIVE: Pseudoxanthoma elasticum is an inherited metabolic disorder resulting
      from ABCC6 gene mutations. It is characterized by progressive calcification and
      fragmentation of elastic fibers in the skin, retina, and the arterial wall.
      Despite calcium accumulation in the arteries of patients with pseudoxanthoma
      elasticum, functional consequences remain unknown. In the present study, we
      investigated arterial structure and function in Abcc6(-/-) mice, a model of the
      human disease. APPROACH AND RESULTS: Arterial calcium accumulation was evaluated
      using alizarin red stain and atomic absorption spectrometry. Expression of genes
      involved in osteochondrogenic differentiation was measured by polymerase chain
      reaction. Elastic arterial properties were evaluated by carotid echotracking.
      Vascular reactivity was evaluated using wire and pressure myography and
      remodeling using histomorphometry. Arterial calcium accumulation was 1.5- to 2
      fold higher in Abcc6(-/-) than in wild-type mice. Calcium accumulated locally
      leading to punctuate pattern. Old Abcc6(-/-) arteries expressed markers of both
      osteogenic (Runx2, osteopontin) and chondrogenic lineage (Sox9, type II
      collagen). Abcc6(-/-) arteries displayed slight increase in arterial stiffness
      and vasoconstrictor tone in vitro tended to be higher in response to
      phenylephrine and thromboxane A2. Pressure-induced (myogenic) tone was
      significantly higher in Abcc6(-/-) arteries than in wild type. Arterial blood
      pressure was not significantly changed in Abcc6(-/-), despite higher variability.
      CONCLUSIONS: Scattered arterial calcium depositions are probably a result of
      osteochondrogenic transdifferentiation of vascular cells. Lower elasticity and
      increased myogenic tone without major changes in agonist-dependent contraction
      evidenced in aged Abcc6(-/-) mice suggest a reduced control of local blood flow,
      which in turn may alter vascular homeostasis in the long term.

PMID- 24675665
TI  - Hepatic overexpression of idol increases circulating protein convertase
      subtilisin/kexin type 9 in mice and hamsters via dual mechanisms: sterol
      regulatory element-binding protein 2 and low-density lipoprotein receptor
      dependent pathways.
AB  - OBJECTIVE: Low-density lipoprotein receptor (LDLR) is degraded by inducible
      degrader of LDLR (Idol) and protein convertase subtilisin/kexin type 9 (PCSK9),
      thereby regulating circulating LDL levels. However, it remains unclear whether,
      and if so how, these LDLR degraders affect each other. We therefore investigated
      effects of liver-specific expression of Idol on LDL/PCSK9 metabolism in mice and
      hamsters. APPROACH AND RESULTS: Injection of adenoviral vector expressing Idol
      (Ad-Idol) induced a liver-specific reduction in LDLR expression which, in turn,
      increased very-low-density lipoprotein/LDL cholesterol levels in wild-type mice
      because of delayed LDL catabolism. Interestingly, hepatic Idol overexpression
      markedly increased plasma PCSK9 levels. In LDLR-deficient mice, plasma PCSK9
      levels were already elevated at baseline and unchanged by Idol overexpression,
      which was comparable with the observation for Ad-Idol-injected wild-type mice,
      indicating that Idol-induced PCSK9 elevation depended on LDLR. In wild-type mice,
      but not in LDLR-deficient mice, Ad-Idol enhanced hepatic PCSK9 expression, with
      activation of sterol regulatory element-binding protein 2 and subsequently
      increased expression of its target genes. Supporting in vivo findings, Idol
      transactivated PCSK9/LDLR in sterol regulatory element-binding protein 2/LDLR
      dependent manners in vitro. Furthermore, an in vivo kinetic study using (125)I
      labeled PCSK9 revealed delayed clearance of circulating PCSK9, which could be
      another mechanism. Finally, to extend these findings into cholesteryl ester
      transfer protein-expressing animals, we repeated the above in vivo experiments in
      hamsters and obtained similar results. CONCLUSIONS: A vicious cycle in LDLR
      degradation might be generated by PCSK9 induced by hepatic Idol overexpression
      via dual mechanisms: sterol regulatory element-binding protein 2/LDLR.
      Furthermore, these effects would be independent of cholesteryl ester transfer
      protein expression.

PMID- 24675669
TI  - Indirect human impacts reverse centuries of carbon sequestration and salt marsh
      accretion.
AB  - Direct and indirect human impacts on coastal ecosystems have increased over the
      last several centuries, leading to unprecedented degradation of coastal habitats
      and loss of ecological services. Here we document a two-century temporal
      disparity between salt marsh accretion and subsequent loss to indirect human
      impacts. Field surveys, manipulative experiments and GIS analyses reveal that
      crab burrowing weakens the marsh peat base and facilitates further burrowing,
      leading to bank calving, disruption of marsh accretion, and a loss of over two
      centuries of sequestered carbon from the marsh edge in only three decades.
      Analogous temporal disparities exist in other systems and are a largely
      unrecognized obstacle in attaining sustainable ecosystem services in an
      increasingly human impacted world. In light of the growing threat of indirect
      impacts worldwide and despite uncertainties in the fate of lost carbon, we
      suggest that estimates of carbon emissions based only on direct human impacts may
      significantly underestimate total anthropogenic carbon emissions. 

PMID- 24675668
TI  - Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3
      kinase/Akt/mTOR pathway.
AB  - We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates
      angiogenic properties similar to those of LL-37 or PR39. However, improvement of
      its stability and cost efficacy are required for clinical application. Therefore,
      we examined the metabolites of AG30/5C, which provided the further optimized
      compound, SR-0379. SR-0379 enhanced the proliferation of human dermal fibroblast
      cells (NHDFs) via the PI3 kinase-Akt-mTOR pathway through integrin-mediated
      interactions. Furthermore SR-0379 promoted the tube formation of human umbilical
      vein endothelial cells (HUVECs) in co-culture with NHDFs. This compound also
      displays antimicrobial activities against a number of bacteria, including drug
      resistant microbes and fungi. We evaluated the effect of SR-0379 in two different
      would-healing models in rats, the full-thickness defects under a diabetic
      condition and an acutely infected wound with full-thickness defects and
      inoculation with Staphylococcus aureus. Treatment with SR-0379 significantly
      accelerated wound healing when compared to fibroblast growth factor 2 (FGF2). The
      beneficial effects of SR-0379 on wound healing can be explained by enhanced
      angiogenesis, granulation tissue formation, proliferation of endothelial cells
      and fibroblasts and antimicrobial activity. These results indicate that SR-0379
      may have the potential for drug development in wound repair, even under
      especially critical colonization conditions. 

PMID- 24675670
TI  - Impact of the common genetic associations of age-related macular degeneration
      upon systemic complement component C3d levels.
AB  - Age-related macular degeneration (AMD) is a common condition that leads to severe
      vision loss and dysregulation of the complement system is thought to be
      associated with the disease. To investigate associations of polymorphisms in AMD
      susceptibility genes with systemic complement activation, 2655 individuals were
      genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD
      associated risk genes. Component 3 (C3) and its catabolic fragment C3d were
      measured in serum and AMD staging was performed using multimodal imaging. The
      C3d/C3 ratio was calculated and associations with environmental factors, SNPs and
      various haplotypes of complement factor H (CFH) genes and complement factor B
      (CFB) genes were analyzed. Linear models were built to measure the influence of
      genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients
      with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p
      = 0.002), higher age (p = 1.56 * 10(-7)), AMD phenotype (p = 1.15 * 10(-11)) and
      the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower
      C3d/C3 ratios were found for diabetes (p = 2.87 * 10(-6)), higher body mass index
      (p = 1.00 * 10(-13)), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003),
      rs12144939 (p = 4.60 * 10(-6)) in CFH, rs4151667 (p = 1.01 * 10(-5)) in CFB and
      individual haplotypes in CFH and CFB. The linear model revealed a corrected R
      square of 0.063 including age, smoking status, gender, and genetic polymorphisms
      explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R
      square was 0.067. In conclusion, none of the evaluated genetic polymorphisms
      showed an association with increased systemic complement activation apart from
      two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not
      associated with systemic complement activation.

PMID- 24675671
TI  - Parametric response maps of perfusion MRI may identify recurrent glioblastomas
      responsive to bevacizumab and irinotecan.
AB  - BACKGROUND: Perfusion weighted imaging (PWI) can be used to measure key aspects
      of tumor vascularity in vivo and recent studies suggest that perfusion imaging
      may be useful in the early assessment of response to angiogenesis inhibitors. Aim
      of this work is to compare Parametric Response Maps (PRMs) with the Region Of
      Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab
      and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in
      tumor blood volume measured by perfusion MRI may predict clinical outcome.
      METHODS: 42 rGBM patients with KPS >= 50 were treated until progression, as
      defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV)
      variation after 8 weeks of treatment was calculated through semi-automatic ROI
      placement in the same anatomic region as in baseline. Alternatively, rCBV
      variations with respect to baseline were calculated into the evolving tumor
      region using a voxel-by-voxel difference. PRMs were created showing where rCBV
      significantly increased, decreased or remained unchanged. RESULTS: An increased
      blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of
      treatment was associated with increased progression free survival (PFS; 24 versus
      13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016).
      After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated
      in non responsive patients (4.8 +/- 0.9 versus 5.1 +/- 1.2, p = 0.38), whereas
      decreased in responsive patients (4.2 +/- 1.3 versus 3.8 +/- 1.6 p = 0.04), and
      re-increased progressively when patients approached tumor progression.
      CONCLUSIONS: Our data suggest that PRMs can provide an early marker of response
      to antiangiogenic treatment and warrant further confirmation in a larger cohort
      of GBM patients.

PMID- 24675672
TI  - Comparative studies of C3 and C4 Atriplex hybrids in the genomics era:
      physiological assessments.
AB  - We crossed the C3 species Atriplex prostrata with the C4 species Atriplex rosea
      to produce F1 and F2 hybrids. All hybrids exhibited C3-like delta(13)C values,
      and had reduced rates of net CO2 assimilation compared with A. prostrata. The
      activities of the major C4 cycle enzymes PEP carboxylase, NAD-malic enzyme, and
      pyruvate-Pi dikinase in the hybrids were at most 36% of the C4 values. These
      results demonstrate the C4 metabolic cycle was disrupted in the hybrids.
      Photosynthetic CO2 compensation points (G) of the hybrids were generally midway
      between the C3 and C4 values, and in most hybrids were accompanied by low, C3
      like activities in one or more of the major C4 cycle enzymes. This supports the
      possibility that most hybrids use a photorespiratory glycine shuttle to
      concentrate CO2 into the bundle sheath cells. One hybrid exhibited a C4-like G of
      4 umol mol(-1), indicating engagement of a C4 metabolic cycle. Consistently, this
      hybrid had elevated activities of all measured C4 cycle enzymes relative to the
      C3 parent; however, C3-like carbon isotope ratios indicate the low G is mainly
      due to a photorespiratory glycine shuttle. The anatomy of the hybrids resembled
      that of C3-C4 intermediate species using a glycine shuttle to concentrate CO2 in
      the bundle sheath, and is further evidence that this physiology is the
      predominant, default condition of the F2 hybrids. Progeny of these hybrids should
      further segregate C3 and C4 traits and in doing so assist in the discovery of C4
      genes using high-throughput methods of the genomics era. 

PMID- 24675673
TI  - Deep sequencing with intronic capture enables identification of an APC exon 10
      inversion in a patient with polyposis.
AB  - PURPOSE: Single-exon inversions have rarely been described in clinical syndromes
      and are challenging to detect using Sanger sequencing. We report the case of a 40
      year-old woman with adenomatous colon polyps too numerous to count and who had a
      complex inversion spanning the entire exon 10 in APC (the gene encoding for
      adenomatous polyposis coli), causing exon skipping and resulting in a frameshift
      and premature protein truncation. METHODS: In this study, we employed complete
      APC gene sequencing using high-coverage next-generation sequencing by ColoSeq,
      analysis with BreakDancer and SLOPE software, and confirmatory transcript
      analysis. RESULTS: ColoSeq identified a complex small genomic rearrangement
      consisting of an inversion that results in translational skipping of exon 10 in
      the APC gene. This mutation would not have been detected by traditional
      sequencing or gene-dosage methods. CONCLUSION: We report a case of adenomatous
      polyposis resulting from a complex single-exon inversion. Our report highlights
      the benefits of large-scale sequencing methods that capture intronic sequences
      with high enough depth of coverage-as well as the use of informatics tools-to
      enable detection of small pathogenic structural rearrangements.

PMID- 24675674
TI  - The natural history of MPS I: global perspectives from the MPS I Registry.
AB  - PURPOSE: In this study, we aimed to describe the natural history of
      mucopolysaccharidosis I. METHODS: Data from 1,046 patients who enrolled in the
      MPS I Registry as of August 2013 were available for descriptive analysis. Only
      data from untreated patients and data prior to treatment for patients who
      received treatment were considered. Age at symptom onset, diagnosis, and
      treatment initiation were examined by geographic region and phenotype (from most
      to least severe: Hurler, Hurler-Scheie, and Scheie). For each symptom, frequency
      and age at onset were examined. RESULTS: Natural history data were available for
      987 patients. Most patients were from Europe (45.5%), followed by North America
      (34.8%), Latin America (17.3%), and Asia Pacific (2.4%). Phenotype distribution
      was 60.9% for Hurler, 23.0% for Hurler-Scheie, and 12.9% for Scheie (3.2%
      undetermined) syndromes. Median age at symptom onset for Hurler, Hurler-Scheie,
      and Scheie syndromes was 6 months, 1.5 years, and 5.3 years, respectively; median
      age at treatment initiation was 1.5 years, 8.0 years, and 16.9 years,
      respectively. Coarse facial features and corneal clouding were among the most
      common symptoms in all three phenotypes. CONCLUSION: A delay between symptom
      onset and treatment exists, especially in patients with attenuated
      mucopolysaccharidosis I. A better understanding of disease manifestations may
      help facilitate prompt diagnosis and treatment and improve patient outcomes.

PMID- 24675675
TI  - A single center's experience with noninvasive prenatal testing.
AB  - PURPOSE: Massively parallel sequencing to detect fetal aneuploidy has high
      sensitivity and specificity for the detection of trisomies 21, 18, and 13 in high
      risk populations. The purpose of our study was to review our institution's
      experience with the use of noninvasive prenatal testing for aneuploidy screening.
      METHODS: This was a descriptive study of patients who had undergone noninvasive
      prenatal testing between January and September 2012 at the UNC Prenatal Diagnosis
      unit. RESULTS: Two hundred and eight women had undergone noninvasive prenatal
      testing during the study period. The majority of patients were white (62.9%) and
      of advanced maternal age (71.2%). The fetal fraction was below the threshold in
      three obese patients (1.4%). An abnormal noninvasive prenatal test (aneuploidy
      detected or "unclassified" result) was reported in 6.3% (13/208) of the patients.
      Noninvasive prenatal testing had a combined sensitivity of 87.5% and specificity
      of 99.5% for detection of trisomies 21, 18, and 13. There were "unclassified"
      results in 11.1% (5/45) of the patients. Over the study period, the number of
      patients requesting noninvasive prenatal testing increased monthly. The rate of
      amniocenteses significantly declined (8.1% before vs. 5.3% after noninvasive
      prenatal testing, P < 0.01). CONCLUSION: An increase in uptake of noninvasive
      prenatal testing and a significant decline in amniocentesis procedures were
      observed. The rates of "unclassified," false-positive, and false-negative results
      were higher than anticipated based on published preclinical trials.

PMID- 24675676
TI  - More ways than one: ERPs reveal multiple familiarity signals in the word
      frequency mirror effect.
AB  - Recent dual-process models of the word frequency mirror effect place absolute
      familiarity, an item's baseline familiarity at a given time point, as responsible
      for false alarm differences and recollection for hit rate differences between
      high and low frequency items. One of the earliest dual-process propositions,
      however, posits an additional relative familiarity mechanism which is sensitive
      to recent presentation but relative to the absolute familiarity of a particular
      item (Mandler, 1980). In this study, it was possible to map these three
      mechanisms onto known event-related potential (ERP) effects in an old/new
      recognition task with high and low frequency words. Contrasts between ERPs
      elicited by high and low frequency new items were assumed to index absolute
      familiarity, and the distribution of this effect from 300 to 600ms was
      topographically distinct from a temporally-overlapping midfrontally-distributed
      old/new effect which was larger for low than high frequency words, as would be
      expected from a relative familiarity mechanism. A later left parietal old/new
      effect, strongly linked to recollection, was only present for low frequency
      items. These frequency-sensitive amplitude differences for both old/new effects
      disappeared in a second recognition task in which old/new decisions were made
      under a time constraint, although the posterior absolute familiarity effect
      remained unaffected by the speeding of responses. The data support the assertion
      that three distinct recognition processes are affected by word frequency in
      recognition memory tasks, and the qualitatively distinct distributions associated
      with the two familiarity contrasts support the presence of two cognitively
      distinct familiarity mechanisms. 

PMID- 24675680
TI  - Metabolomics in hypertension.
AB  - Hypertension is the most prevalent chronic medical condition and a major risk
      factor for cardiovascular morbidity and mortality. In the majority of
      hypertensive cases, the underlying cause of hypertension cannot be easily
      identified because of the heterogeneous, polygenic and multi-factorial nature of
      hypertension. Metabolomics is a relatively new field of research that has been
      used to evaluate metabolic perturbations associated with disease, identify
      disease biomarkers and to both assess and predict drug safety and efficacy.
      Metabolomics has been increasingly used to characterize risk factors for
      cardiovascular disease, including hypertension, and it appears to have
      significant potential for uncovering mechanisms of this complex disease. This
      review details the analytical techniques, pre-analytical steps and study designs
      used in metabolomics studies, as well as the emerging role for metabolomics in
      gaining mechanistic insights into the development of hypertension. Suggestions as
      to the future direction for metabolomics research in the field of hypertension
      are also proposed. 

PMID- 24675677
TI  - CDKN2D-WDFY2 is a cancer-specific fusion gene recurrent in high-grade serous
      ovarian carcinoma.
AB  - Ovarian cancer is the fifth leading cause of cancer death in women. Almost 70% of
      ovarian cancer deaths are due to the high-grade serous subtype, which is
      typically detected only after it has metastasized. Characterization of high-grade
      serous cancer is further complicated by the significant heterogeneity and genome
      instability displayed by this cancer. Other than mutations in TP53, which is
      common to many cancers, highly recurrent recombinant events specific to this
      cancer have yet to be identified. Using high-throughput transcriptome sequencing
      of seven patient samples combined with experimental validation at DNA, RNA and
      protein levels, we identified a cancer-specific and inter-chromosomal fusion gene
      CDKN2D-WDFY2 that occurs at a frequency of 20% among sixty high-grade serous
      cancer samples but is absent in non-cancerous ovary and fallopian tube samples.
      This is the most frequent recombinant event identified so far in high-grade
      serous cancer implying a major cellular lineage in this highly heterogeneous
      cancer. In addition, the same fusion transcript was also detected in OV-90, an
      established high-grade serous type cell line. The genomic breakpoint was
      identified in intron 1 of CDKN2D and intron 2 of WDFY2 in patient tumor,
      providing direct evidence that this is a fusion gene. The parental gene, CDKN2D,
      is a cell-cycle modulator that is also involved in DNA repair, while WDFY2 is
      known to modulate AKT interactions with its substrates. Transfection of cloned
      fusion construct led to loss of wildtype CDKN2D and wildtype WDFY2 protein
      expression, and a gain of a short WDFY2 protein isoform that is presumably under
      the control of the CDKN2D promoter. The expression of short WDFY2 protein in
      transfected cells appears to alter the PI3K/AKT pathway that is known to play a
      role in oncogenesis. CDKN2D-WDFY2 fusion could be an important molecular
      signature for understanding and classifying sub-lineages among heterogeneous high
      grade serous ovarian carcinomas. 

PMID- 24675681
TI  - Prevalence, awareness, treatment and control of hypertension and salt intake in
      Portugal: changes over a decade. The PHYSA study.
AB  - OBJECTIVE: To determine prevalence, awareness, treatment and control of
      hypertension and the 24-h sodium excretion (24h-UNa) in the Portuguese adult
      population and to examine their changes from a similar study done in 2003. DESIGN
      AND SETTING: A population-based cross-sectional survey conducted in 2011-2012.
      METHODS: A multistage-stratified (by age and sex) sampling method was used to
      select a representative sample of the 18-90-year-old population yielding 3720
      participants (52.6% women, 97.1% Caucasians). Hypertension was defined as a SBP
      of at least 140  mmHg or DBP of at least 90  mmHg [average of 2-3 blood pressure
      (BP) measurements by trained observers with OMRON M6] or reported knowledge or
      treatment with antihypertensive drugs at the first visit (V1). A complete
      clinical information was obtained with a standard questionnaire. This procedure
      was repeated 10-15 days after visit 2 (V2) and 24-h urinary sample was collected
      for 24h-UNa, 24-h potassium excretion and creatinine excretion. RESULTS: The
      overall prevalence of hypertension at V1 was 42.2% (44.4% in men, 40.2% in women)
      (42.1% in 2003). The age-specific prevalence of hypertension was 6.8, 46.9 and
      74.9% in people below 35 years, 35-64 years and above 64 years. Comorbidities
      were 2.2-6.3 times more common in hypertensive patients vs. normotensive
      individuals. Overall, among the hypertensive patients, 76.6% were aware of the
      hypertension condition, 74.9% were treated and 42.5% were controlled (BP <140/90 
      mmHg), that is, respectively, 1.7, 1.9 and 3.8 times higher vs. data in 2003,
      with lower values in men vs. women and younger vs. older people. Global mean BP
      was 127.4/74.6 +/- 17.7/10.5 vs. 134.7/80.4 +/- 21.2/14.1  mmHg in 2003. From V1
      to V2, control of hypertension increased on average by 14.8%. Multivariate
      analysis showed that age and BMI were independently associated with prevalence of
      hypertension. 24h-UNa (84% valid urinary samples) was 182.5 +/- 64.7  mmol/day
      (10.7  g salt/day) and 24-h potassium excretion 75.2 +/- 26.1  mmol/day. 24h-UNa
      was higher in patients with hypertension than in normotensive individuals (185.4
      +/- 64.8 vs. 177.8 +/- 64.5  mmol/day; P < 0.02) and correlated with SBP (r =
      0.05), age (r = 0.08) and BMI (r = 0.10) (P < 0.01). CONCLUSION: Hypertension
      prevalence among Portuguese adults remained stable in the past decade, but
      proportions of awareness, treatment and control of hypertension improved
      significantly. Salt intake is still high being almost double the WHO
      recommendations.

PMID- 24675682
TI  - Prognostic value of serum uric acid: new-onset in and out-of-office hypertension
      and long-term mortality.
AB  - OBJECTIVE: Serum uric acid (SUA) has been associated with an increased
      cardiovascular risk, but no conclusive evidence exists on whether it is an
      independent risk factor or a reflection of other risk factors to which it is
      related. We examined the relationship of SUA with a number of cardiovascular
      variables [including risk factors never evaluated before, such as organ damage
      and out-of-office blood pressure (BP)], as well as its prognostic relevance in
      the population. METHODS: In 2045 participants of the Pressioni Arteriose
      Monitorate E Loro Associazioni study, we measured, along with SUA, metabolic,
      renal, and anthropometric variables, left-ventricular mass index, and office,
      home and ambulatory BP. Cardiovascular and all-cause mortality was assessed over
      a 16-year follow-up period, and measurements were repeated 10 years after the
      initial data collection. RESULTS: Baseline SUA had a near-normal distribution,
      with a mean value of 4.9 +/- 1.3 (SD) mg/dl and a significant direct relationship
      with BP and metabolic variables, serum creatinine and left-ventricular mass
      index. It was among the factors independently predicting new-onset home and
      ambulatory hypertension, the increased risk of developing these conditions for 1 
      mg/dl increase of SUA after adjustment for all available potential confounders
      being 34 and 29%, respectively (P = 0.015 and P = 0.014). An increase in SUA of 1
      mg/dl also independently predicted cardiovascular and all-cause mortality, the
      fully adjusted increase in risk being 22% (P = 0.03) and 12% (P = 0.04),
      respectively. CONCLUSION: In the general population of the Pressioni Arteriose
      Monitorate E Loro Associazioni study, SUA correlated with a number of
      cardiovascular risk factors. Nevertheless, it independently predicts new-onset
      out-of-office hypertension, and long-term cardiovascular and all-cause mortality.

PMID- 24675683
TI  - Targeting impulsive processes of eating behavior via the internet. Effects on
      body weight.
AB  - Because eating behavior can take on an impulsive nature many people experience
      difficulty with dieting to lose weight. Therefore, an experiment was conducted to
      test the effectiveness of two interventions targeting impulsive processes of
      eating behavior to facilitate weight loss: Implementation intentions to remind
      people about dieting versus a go/no-go task to change impulses toward palatable
      foods. Dieters performed an online training program (four times in 4 weeks) in
      which they were randomly assigned to a 2 (implementation intention condition:
      dieting versus control) * 2 (go/no-go task condition: food versus control)
      design. They formed either dieting implementation intentions (e.g., If I open the
      fridge I will think of dieting!) or control implementation intentions.
      Furthermore, they received either a go/no-go task in which behavioral stop
      signals were presented upon presentation of palatable foods (food go/no-go task),
      or upon control stimuli. Participants' weight was measured in the laboratory
      before and after the intervention. Strength of participants' dieting goal and
      their Body Mass Index (BMI; as a proxy for impulsiveness toward food) were
      examined as moderators. Results showed that both dieting implementation
      intentions and the food go/no-go task facilitated weight loss. Moreover, dieting
      implementation intentions facilitated weight loss particularly among people with
      a strong current dieting goal, whereas the food go/no-go task facilitated weight
      loss independent of this factor. Instead, the food go/no-go task, but not
      formation of dieting implementation intentions, was primarily effective among
      dieters with a relatively high BMI. These results provide the first preliminary
      evidence that interventions aimed at targeting impulsive eating-related processes
      via the internet can facilitate weight loss. 

PMID- 24675684
TI  - Meloxicam executes its antitumor effects against hepatocellular carcinoma in COX
      2- dependent and -independent pathways.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 is overexpressed in many types of cancers
      including hepatocellular carcinoma (HCC). Meloxicam, a selective COX-2 inhibitor,
      has shown potential therapeutic effects against HCC, but the mechanisms
      accounting for its anti-cancer activities remain unclear. METHODS AND FINDINGS:
      Meloxicam inhibited the ability of human HCC cells expressing higher levels of
      COX-2 to migrate, invade, adhere and form colonies through upregulating the
      expression of E-cadherin and downregulating the expression of matrix
      metalloproteinase (MMP) -2. Meloxicam induced cell apoptosis by upregulating pro
      apoptotic proteins including Bax and Fas-L, and downregulating anti-apoptotic
      proteins including survivin and myeloid cell leukemia-1 (Mcl-1), through
      inhibiting phosphorylation of AKT. Addition of prostaglandin E2 (PGE2), the major
      product of COX-2, could abrogate the effects of meloxicam on the expression of
      survivin and myeloid cell leukemia-1 (Mcl-1), but not Bax and Fas-L, indicating
      that meloxicam induces cell apoptosis via both COX-2-dependent and -independent
      pathways. Meloxicam also induced cell autophagy by upregulating Beclin 1 and
      light chain 3-II. Specific inhibition of autophagy by 3-methyladenine and
      chloroquine had little effect on cell apoptosis but could enhance the pro
      apoptotic effects of meloxicam by further upregulating the expression of Bax.
      CONCLUSIONS: Meloxicam executes its antitumor effects by targeting the COX-2/MMP
      2/E-cadherin, AKT, apoptotic and autophagic pathways in COX-2-dependent and 
      independent pathways, and inhibition of cell autophagy could help to overcome the
      resistance to meloxicam-induced apoptosis in HCC.

PMID- 24675685
TI  - HapTree: a novel Bayesian framework for single individual polyplotyping using NGS
      data.
AB  - As the more recent next-generation sequencing (NGS) technologies provide longer
      read sequences, the use of sequencing datasets for complete haplotype phasing is
      fast becoming a reality, allowing haplotype reconstruction of a single sequenced
      genome. Nearly all previous haplotype reconstruction studies have focused on
      diploid genomes and are rarely scalable to genomes with higher ploidy. Yet
      computational investigations into polyploid genomes carry great importance,
      impacting plant, yeast and fish genomics, as well as the studies of the evolution
      of modern-day eukaryotes and (epi)genetic interactions between copies of genes.
      In this paper, we describe a novel maximum-likelihood estimation framework,
      HapTree, for polyploid haplotype assembly of an individual genome using NGS read
      datasets. We evaluate the performance of HapTree on simulated polyploid
      sequencing read data modeled after Illumina sequencing technologies. For triploid
      and higher ploidy genomes, we demonstrate that HapTree substantially improves
      haplotype assembly accuracy and efficiency over the state-of-the-art; moreover,
      HapTree is the first scalable polyplotyping method for higher ploidy. As a proof
      of concept, we also test our method on real sequencing data from NA12878 (1000
      Genomes Project) and evaluate the quality of assembled haplotypes with respect to
      trio-based diplotype annotation as the ground truth. The results indicate that
      HapTree significantly improves the switch accuracy within phased haplotype blocks
      as compared to existing haplotype assembly methods, while producing comparable
      minimum error correction (MEC) values. A summary of this paper appears in the
      proceedings of the RECOMB 2014 conference, April 2-5. 

PMID- 24675688
TI  - A sulfur mimic of 1,1-bis(diphenylphosphino)methane: a new ligand opens up.
AB  - A simple method for synthesizing diphosphine monosulfide species was developed
      utilizing lithium sulfide and chlorophosphine starting materials. This afforded
      1,1,2,2-tetraphenyldiphosphine monosulfide (1), as well as 1,1,2,2
      tetracyclohexyldiphosphine monosulfide (2), which could be used as convenient
      ligand precursors. Upon addition of 1 or 2 to the ruthenium compound
      Ru(C5Me5)(cod)Cl, the diphosphine monosulfides rearranged to give bidentate
      bis(ditertiaryphosphino)thioether ligands in Ru(C5Me5)(PPh2SPPh2)Cl (3) and
      Ru(C5Me5)(PCy2SPCy2)Cl (4).

PMID- 24675693
TI  - Visualizing the influence of point defects on the electronic band structure of
      graphene.
AB  - The supercell approach enables us to treat the electronic structure of defective
      crystals, but the calculated energy bands are too complicated to understand or
      compare with angle-resolved photoemission spectra because of inevitable zone
      folding. We discuss how to visualize supercell band structures more effectively
      by incorporating unfolded spectral weights and orbital decompositions into them.
      We then apply these ideas to gain a better understanding of the band structure of
      graphene containing various types of point defects, including nitrogen impurity,
      hydrogen adsorbate, vacancy defects and the Stone-Wales defect. 

PMID- 24675689
TI  - Proximity to sports facilities and sports participation for adolescents in
      Germany.
AB  - OBJECTIVES: To assess the relationship between proximity to specific sports
      facilities and participation in the corresponding sports activities for
      adolescents in Germany. METHODS: A sample of 1,768 adolescents aged 11-17 years
      old and living in 161 German communities was examined. Distances to the nearest
      sports facilities were calculated as an indicator of proximity to sports
      facilities using Geographic Information Systems (GIS). Participation in specific
      leisure-time sports activities in sports clubs was assessed using a self-report
      questionnaire and individual-level socio-demographic variables were derived from
      a parent questionnaire. Community-level socio-demographics as covariates were
      selected from the INKAR database, in particular from indicators and maps on land
      development. Logistic regression analyses were conducted to examine associations
      between proximity to the nearest sports facilities and participation in the
      corresponding sports activities. RESULTS: The logistic regression analyses showed
      that girls residing longer distances from the nearest gym were less likely to
      engage in indoor sports activities; a significant interaction between distances
      to gyms and level of urbanization was identified. Decomposition of the
      interaction term showed that for adolescent girls living in rural areas
      participation in indoor sports activities was positively associated with gym
      proximity. Proximity to tennis courts and indoor pools was not associated with
      participation in tennis or water sports, respectively. CONCLUSIONS: Improved
      proximity to gyms is likely to be more important for female adolescents living in
      rural areas.

PMID- 24675692
TI  - Interferon regulatory factor-1 protects from fatal neurotropic infection with
      vesicular stomatitis virus by specific inhibition of viral replication in
      neurons.
AB  - The innate immune system protects cells against invading viral pathogens by the
      auto- and paracrine action of type I interferon (IFN). In addition, the
      interferon regulatory factor (IRF)-1 can induce alternative intrinsic antiviral
      responses. Although both, type I IFN and IRF-1 mediate their antiviral action by
      inducing overlapping subsets of IFN stimulated genes, the functional role of this
      alternative antiviral action of IRF-1 in context of viral infections in vivo
      remains unknown. Here, we report that IRF-1 is essential to counteract the
      neuropathology of vesicular stomatitis virus (VSV). IFN- and IRF-1-dependent
      antiviral responses act sequentially to create a layered antiviral protection
      program against VSV infections. Upon intranasal infection, VSV is cleared in the
      presence or absence of IRF-1 in peripheral organs, but IRF-1-/- mice continue to
      propagate the virus in the brain and succumb. Although rapid IFN induction leads
      to a decline in VSV titers early on, viral replication is re-enforced in the
      brains of IRF-1-/- mice. While IFN provides short-term protection, IRF-1 is
      induced with delayed kinetics and controls viral replication at later stages of
      infection. IRF-1 has no influence on viral entry but inhibits viral replication
      in neurons and viral spread through the CNS, which leads to fatal inflammatory
      responses in the CNS. These data support a temporal, non-redundant antiviral
      function of type I IFN and IRF-1, the latter playing a crucial role in late time
      points of VSV infection in the brain. 

PMID- 24675694
TI  - Poor prognosis of hypocoagulability assessed by thrombin generation assay in
      disseminated intravascular coagulation.
AB  - Overall assessment of the hemostatic system including procoagulant and
      anticoagulant changes may help assess the clinical status and prognosis of
      disseminated intravascular coagulation (DIC). The thrombin generation assay
      provides useful information about the global hemostatic status. Therefore, we
      measured several parameters of global hemostatic potential by the thrombin
      generation assay in patients suspected of having DIC. A total of 114 patients
      with suspected DIC were included. The thrombin generation assay was performed on
      the calibrated automated thrombogram using tissue factor with or without the
      addition of thrombomodulin, showing three parameters: lag time, endogenous
      thrombin potential (ETP), and peak thrombin. Both 1 and 5 pmol/l tissue factor
      stimulated ETP and peak thrombin were well correlated with DIC severity.
      Interestingly, antithrombin level greatly affected ETP, whereas protein C
      influenced lag time. Prognostic analysis revealed that the area under the curve
      of peak thrombin stimulated by 1 pmol/l tissue factor was superior to that of D
      dimer. Moreover, multivariate Cox analysis showed that the lag time and time to
      peak with both 1 and 5 pmol/l tissue factor were independent prognostic markers.
      ETP and peak thrombin well reflect DIC severity. Hypocoagulability manifesting as
      prolonged lag time and time to peak is expected to be an independent prognostic
      marker in DIC. 

PMID- 24675695
TI  - Factor V deficiency caused by a novel nonsense mutation (Gln2031stop) in a
      Chinese patient.
AB  - Congenital factor V deficiency is a rare bleeding disorder characterized by low
      coagulant activity, associated with variable phenotypic expression. Among rare
      inherited coagulopathies, the molecular basis of factor V deficiency is rarely
      described because of its relatively low prevalence in the general population.
      Recently, we detected two genetic variations in factor V of a Chinese patient
      with hereditary factor V deficiency. One was a heterozygous nonsense mutation,
      C67868T in exon 22, which resulted in Gln2031stop substitution in the C1 domain
      of factor V. The other was a previously described polymorphism, G1618A in exon10,
      leading to Arg485Lys substitution. We deduced that the nonsense mutation is
      responsible for the factor V deficiency, whereas the Arg485Lys polymorphism is
      expected to compensate for the low plasma factor V levels. Of note, the nonsense
      mutation has been confirmed to be a novel mutation. 

PMID- 24675696
TI  - Antibacterial activity of new oxazolidin-2-one analogues in methicillin-resistant
      Staphylococcus aureus strains.
AB  - Staphylococcus aureus is one of the most common causes of nosocomial infections.
      The purpose of this study was the synthesis and in vitro evaluation of
      antimicrobial activity of 10 new 3-oxazolidin-2-one analogues on 12 methicillin
      resistant S. aureus (MRSA) clinical isolates. S. aureus confirmation was achieved
      via catalase and coagulase test. Molecular characterization of MRSA was performed
      by amplification of the mecA gene. Antimicrobial susceptibility was evaluated via
      the Kirby-Bauer disc diffusion susceptibility test protocol, using commonly
      applied antibiotics and the oxazolidinone analogues. Only (R)-5-((S)-1
      dibenzylaminoethyl)-1,3-oxazolidin-2-one (7a) exhibited antibacterial activity at
      6.6 MUg. These results, allow us to infer that molecules such as 7a can be
      potentially used to treat infections caused by MRSA strains. 

PMID- 24675697
TI  - Beclin 1 expression in ovarian tissues and its effects on ovarian cancer
      prognosis.
AB  - Beclin 1 is an autophagy-associated protein involved in apoptosis and drug
      resistance, as well as various malignancies. We investigated the expression of
      Beclin 1 protein in ovarian epithelial tissues and correlated it with the
      prognosis of ovarian cancer. Beclin 1 protein expression was determined using
      immunohistochemistry in 148 patients with ovarian epithelial cancer, 26 with
      ovarian borderline tumor, 25 with benign ovarian tumor, and 30 with normal
      ovarian tissue. The relationships between Beclin 1 protein expression and ovarian
      cancer pathological characteristics were analyzed. The risk factors for ovarian
      cancer prognosis were analyzed using Cox's regression model. A survival curve was
      plotted from the follow-up data of 93 patients with ovarian cancer to analyze the
      effects of Beclin 1 expression on the prognosis of ovarian cancer. The positive
      rates of Beclin 1 were significantly higher in ovarian epithelial cancer (148)
      and borderline tumor (26) than in benign ovarian tumor (25) or normal ovarian
      tissue (30) (all p<0.001). The surgical stage and Beclin 1 expression were both
      independent risk factors for ovarian cancer prognosis (both p<0.05). Patients
      with high Beclin 1 levels showed better survival than those with low Beclin 1
      levels (p=0.009). Beclin 1 protein is upregulated in ovarian epithelial cancer
      and is a prognostic factor of ovarian cancer.

PMID- 24675698
TI  - Aerobic interval training attenuates mitochondrial dysfunction in rats post
      myocardial infarction: roles of mitochondrial network dynamics.
AB  - Aerobic interval training (AIT) can favorably affect cardiovascular diseases.
      However, the effects of AIT on post-myocardial infarction (MI)-associated
      mitochondrial dysfunctions remain unclear. In this study, we investigated the
      protective effects of AIT on myocardial mitochondria in post-MI rats by focusing
      on mitochondrial dynamics (fusion and fission). Mitochondrial respiratory
      functions (as measured by the respiratory control ratio (RCR) and the ratio of
      ADP to oxygen consumption (P/O)); complex activities; dynamic proteins (mitofusin
      (mfn) 1/2, type 1 optic atrophy (OPA1) and dynamin-related protein1 (DRP1));
      nuclear peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha); and the oxidative signaling of extracellular signal-regulated kinase
      (ERK) 1/2, c-Jun NH2-terminal protein kinase (JNK) and P53 were observed. Post-MI
      rats exhibited mitochondrial dysfunction and adverse mitochondrial network
      dynamics (reduced fusion and increased fission), which was associated with
      activated ERK1/2-JNK-P53 signaling and decreased nuclear PGC-1alpha. After AIT,
      MI-associated mitochondrial dysfunction was improved (elevated RCR and P/O and
      enhanced complex I, III and IV activities); in addition, increased fusion (mfn2
      and OPA1), decreased fission (DRP1), elevated nuclear PGC-1alpha and inactivation
      of the ERK1/2-JNK-P53 signaling were observed. These data demonstrate that AIT
      may restore the post-MI mitochondrial function by inhibiting dynamics
      pathological remodeling, which may be associated with inactivation of ERK1/2-JNK
      P53 signaling and increase in nuclear PGC-1alpha expression. 

PMID- 24675699
TI  - Role of VEGF-A and its receptors in sporadic and MEN2-associated
      pheochromocytoma.
AB  - Pheochromocytoma (PHEO), a rare catecholamine producing tumor arising from the
      chromaffin cells, may occurs sporadically (76%-80%) or as part of inherited
      syndromes (20%-24%). Angiogenesis is a fundamental step in tumor proliferation
      and vascular endothelial growth factor (VEGF-A) is the most well-characterized
      angiogenic factor. The role of angiogenic markers in PHEO is not fully
      understood; investigations were therefore made to evaluate the expression of VEGF
      A and its receptors in PHEO and correlate to clinical parameters. Twenty-nine
      samples of PHEO were evaluated for VEGF-A, VEGF receptor-1 (VEGFR-1) VEGFR-2
      expression and microvessel density (MVD) by immunohistochemistry. Clinical data
      were reviewed in medical records. The mean age of patients was 38+/-14 years, and
      69% were woman. VEGF-A, VEGFR-1 and VEGFR-2 staining were detected in nearly all
      PHEO samples. No significant correlation was observed between VEGF-A, VEGFR-1,
      VEGFR-2 expression or MVD and age at diagnosis, tumor size or sporadic and
      hereditary PHEO. However, the levels of expression of these molecules were
      significantly higher in malignant PHEO samples (p=0.027, p=0.003 and p=0.026,
      respectively).VEGF-A and its receptors were shown to be up-regulated in malignant
      PHEO, suggesting that these molecules might be considered as therapeutic targets
      for unresectable or metastatic tumors.

PMID- 24675700
TI  - Diversification and repeated morphological transitions in endoparasitic
      cnidarians (Myxozoa: Malacosporea).
AB  - Malacosporeans are a poorly known myxozoan clade that uniquely demonstrates a
      tissue level of organisation. Thus, when exploiting their invertebrate hosts
      (freshwater bryozoans) they occur as non-motile sacs or vermiform stages capable
      of active swimming. We combine phylogenetic analyses of SSU and LSU rDNA with
      morphological observations to substantially enhance understanding of
      malacosporean diversification. The phylogenetic analyses incorporate the widest
      taxon sampling and geographic cover to date, reveal four novel malacosporean
      lineages and several putatively new species, one with a novel morphology of
      irregular, bulbous sacs and no musculature. This lineage currently forms the
      earliest branch of malacosporeans. Vermiform stages may have been lost or gained
      several times within the Malacosporea, even in cases where SSU sequence
      divergence is very low. Yet, sac and vermiform Buddenbrockia plumatellae appear
      to be separate species, an inference also supported by their utilisation of
      different bryozoan hosts. Cryptic speciation is also apparent with two novel,
      genetically divergent lineages (novel lineage 2 and Buddenbrockia sp. 4) being
      morphologically indistinguishable from known species. Finally, we provide
      evidence that fredericellid bryozoans are the main hosts for Tetracapsuloides
      bryosalmonae and are therefore most relevant for research on the ecology and
      management of Proliferative Kidney Disease of salmonid fish. 

PMID- 24675701
TI  - Evolutionary diversification of aminopeptidase N in Lepidoptera by conserved
      clade-specific amino acid residues.
AB  - Members of the aminopepidase N (APN) gene family of the insect order Lepidoptera
      (moths and butterflies) bind the naturally insecticidal Cry toxins produced by
      the bacterium Bacillus thuringiensis. Phylogenetic analysis of amino acid
      sequences of seven lepidopteran APN classes provided strong support for the
      hypothesis that lepidopteran APN2 class arose by gene duplication prior to the
      most recent common ancestor of Lepidoptera and Diptera. The Cry toxin-binding
      region (BR) of lepidopteran and dipteran APNs was subject to stronger purifying
      selection within APN classes than was the remainder of the molecule, reflecting
      conservation of catalytic site and adjoining residues within the BR. Of
      lepidopteran APN classes, APN2, APN6, and APN8 showed the strongest evidence of
      functional specialization, both in expression patterns and in the occurrence of
      conserved derived amino acid residues. The latter three APN classes also shared a
      convergently evolved conserved residue close to the catalytic site. APN8 showed a
      particularly strong tendency towards class-specific conserved residues, including
      one of the catalytic site residues in the BR and ten others in close vicinity to
      the catalytic site residues. The occurrence of class-specific sequences along
      with the conservation of enzymatic function is consistent with the hypothesis
      that the presence of Cry toxins in the environment has been a factor shaping the
      evolution of this multi-gene family. 

PMID- 24675706
TI  - Broadband absorption engineering of hyperbolic metafilm patterns.
AB  - Perfect absorbers are important optical/thermal components required by a variety
      of applications, including photon/thermal-harvesting, thermal energy recycling,
      and vacuum heat liberation. While there is great interest in achieving highly
      absorptive materials exhibiting large broadband absorption using optically thick,
      micro-structured materials, it is still challenging to realize ultra-compact
      subwavelength absorber for on-chip optical/thermal energy applications. Here we
      report the experimental realization of an on-chip broadband super absorber
      structure based on hyperbolic metamaterial waveguide taper array with strong and
      tunable absorption profile from near-infrared to mid-infrared spectral region.
      The ability to efficiently produce broadband, highly confined and localized
      optical fields on a chip is expected to create new regimes of optical/thermal
      physics, which holds promise for impacting a broad range of energy technologies
      ranging from photovoltaics, to thin-film thermal absorbers/emitters, to optical
      chemical energy harvesting. 

PMID- 24675707
TI  - Resistin in dairy cows: plasma concentrations during early lactation, expression
      and potential role in adipose tissue.
AB  - Resistin is an adipokine that has been implicated in energy metabolism regulation
      in rodents but has been little studied in dairy cows. We determined plasma
      resistin concentrations in early lactation in dairy cows and investigated the
      levels of resistin mRNA and protein in adipose tissue and the phosphorylation of
      several components of insulin signaling pathways one week post partum (1 WPP) and
      at five months of gestation (5 MG). We detected resistin in mature bovine
      adipocytes and investigated the effect of recombinant bovine resistin on
      lipolysis in bovine adipose tissue explants. ELISA showed that plasma resistin
      concentration was low before calving, subsequently increasing and reaching a peak
      at 1 WPP, decreasing steadily thereafter to reach pre-calving levels at 6 WPP.
      Plasma resistin concentration was significantly positively correlated with plasma
      non esterified fatty acid (NEFA) levels and negatively with milk yield, dry
      matter intake and energy balance between WPP1 to WPP22. We showed, by
      quantitative RT-PCR and western blotting, that resistin mRNA and protein levels
      in adipose tissue were higher at WPP1 than at 5 MG. The level of phosphorylation
      of several early and downstream insulin signaling components (IRbeta, IRS-1, IRS
      2, Akt, MAPK ERK1/2, P70S6K and S6) in adipose tissue was also lower at 1 WPP
      than at 5 MG. Finally, we showed that recombinant bovine resistin increased the
      release of glycerol and mRNA levels for ATGL (adipose triglyceride lipase) and
      HSL (hormone-sensitive lipase) in adipose tissue explants. Overall, resistin
      levels were high in the plasma and adipose tissue and were positively correlated
      with NEFA levels after calving. Resistin is expressed in bovine mature adipocytes
      and promotes lipid mobilization in adipose explants in vitro. 

PMID- 24675708
TI  - Childhood poverty and stress reactivity are associated with aberrant functional
      connectivity in default mode network.
AB  - Convergent research suggests that childhood poverty is associated with
      perturbation in the stress response system. This might extend to aberrations in
      the connectivity of large-scale brain networks, which subserve key cognitive and
      emotional functions. Resting-state brain activity was measured in adults with a
      documented history of childhood poverty (n=26) and matched controls from middle
      income families (n=26). Participants also underwent a standard laboratory social
      stress test and provided saliva samples for cortisol assay. Childhood poverty was
      associated with reduced default mode network (DMN) connectivity. This, in turn,
      was associated with higher cortisol levels in anticipation of social stress.
      These results suggest a possible brain basis for exaggerated stress sensitivity
      in low-income individuals. Alterations in DMN may be associated with less
      efficient cognitive processing or greater risk for development of stress-related
      psychopathology among individuals who experienced the adversity of chronic
      childhood poverty. 

PMID- 24675709
TI  - Exploring the use of thermal infrared imaging in human stress research.
AB  - High resolution thermal infrared imaging is a pioneering method giving indices of
      sympathetic activity via the contact-free recording of facial tissues (thermal
      imprints). Compared to established stress markers, the great advantage of this
      method is its non-invasiveness. The goal of our study was to pilot the use of
      thermal infrared imaging in the classical setting of human stress research.
      Thermal imprints were compared to established stress markers (heart rate, heart
      rate variability, finger temperature, alpha-amylase and cortisol) in 15
      participants undergoing anticipation, stress and recovery phases of two
      laboratory stress tests, the Cold Pressor Test and the Trier Social Stress Test.
      The majority of the thermal imprints proved to be change-sensitive in both tests.
      While correlations between the thermal imprints and established stress markers
      were mostly non-significant, the thermal imprints (but not the established stress
      makers) did correlate with stress-induced mood changes. Multivariate pattern
      analysis revealed that in contrast to the established stress markers the thermal
      imprints could not disambiguate anticipation, stress and recovery phases of both
      tests. Overall, these results suggest that thermal infrared imaging is a valuable
      method for the estimation of sympathetic activity in the stress laboratory
      setting. The use of this non-invasive method may be particularly beneficial for
      covert recordings, in the study of special populations showing difficulties in
      complying with the standard instruments of data collection and in the domain of
      psychophysiological covariance research. Meanwhile, the established stress
      markers seem to be superior when it comes to the characterization of complex
      physiological states during the different phases of the stress cycle. 

PMID- 24675710
TI  - alpha-Dihydroxychalcone-glycoside (alpha-DHC) isolated from the heartwood of
      Pterocarpus marsupium inhibits LPS induced MAPK activation and up regulates HO-1
      expression in murine RAW 264.7 macrophage.
AB  - Three phenolic glycosides isolated from the heartwood of Pterocarpus marsupium
      showed significant free radical and superoxide ion scavenging activity and
      antioxidant potential that were comparable to, or several folds higher than those
      of standard antioxidants, trolox and ascorbic acid. The effective concentrations
      of these compounds were far below their cytotoxic levels. Compound 3, which was
      characterized to be alpha-dihydroxychalcone-glycoside (alpha-DHC), was the most
      potent one. Subsequent studies demonstrated that alpha-DHC effectively reduced
      nitric oxide and cytokine production by the LPS stimulated RAW 264.7 mouse
      macrophage cell line. The compound effectively attenuated the expression of
      inflammation-mediating enzymes COX-2 and iNOS at the mRNA as well as protein
      levels in a concentration dependent manner. It prevented phosphorylation of all
      the three MAPKs (JNK, ERK, p38) and eventually blocked the activation of
      downstream elements contributing to inflammation. Phosphorylation of IkappaB
      alpha and subsequent translocation of NF-kappaB into the nucleus were restricted,
      while the expression of stress responsive gene HO-1 was up-regulated. alpha-DHC
      targeted Keap-1 by modifying its cysteine thiols, dissociating it from Nrf-2 and
      facilitating nuclear entry of the latter; and this in turn induced HO-1
      expression. Thus alpha-DHC exerts its anti-inflammatory activity in a dual
      manner: by down regulating MAPKs and restricting nuclear stabilization of NF
      kappaB at one end, and by disrupting Nrf-2-Keap-1 complex on the other. In
      conclusion, the anti-inflammatory potential together with its high therapeutic
      index envisages alpha-DHC as a prospective candidate molecule for the development
      of therapeutic strategy against inflammatory disorders. 

PMID- 24675712
TI  - Scientific activity is a better predictor of nobel award chances than dietary
      habits and economic factors.
AB  - Several recent studies have described a strong correlation between nutritional or
      economic data and the number of Nobel awards obtained across a large range of
      countries. This sheds new light on the intriguing question of the key predictors
      of Nobel awards chances. However, all these studies have been focused on a single
      predictor and were only based on simple correlation and/or linear model analysis.
      The main aim of the present study was thus to clarify this debate by
      simultaneously exploring the influence of food consumption (cacao, milk, and
      wine), economic variables (gross domestic product) and scientific activity
      (number of publications and research expenditure) on Nobel awards. An innovative
      statistical analysis, hierarchical partitioning, has been used because it enables
      us to reduce collinearity problems by determining and comparing the independent
      contribution of each factor. Our results clearly indicate that a country's number
      of Nobel awards can be mainly predicted by its scientific achievements such as
      number of publications and research expenditure. Conversely, dietary habits and
      the global economy variable are only minor predictors; this finding contradicts
      the conclusions of previous studies. Dedicating a large proportion of the GDP to
      research and to the publication of a high number of scientific papers would thus
      create fertile ground for obtaining Nobel awards. 

PMID- 24675711
TI  - Enhanced protective efficacy of nonpathogenic recombinant leishmania tarentolae
      expressing cysteine proteinases combined with a sand fly salivary antigen.
AB  - BACKGROUND: Novel vaccination approaches are needed to prevent leishmaniasis.
      Live attenuated vaccines are the gold standard for protection against
      intracellular pathogens such as Leishmania and there have been new developments
      in this field. The nonpathogenic to humans lizard protozoan parasite, Leishmania
      (L) tarentolae, has been used effectively as a vaccine platform against visceral
      leishmaniasis in experimental animal models. Correspondingly, pre-exposure to
      sand fly saliva or immunization with a salivary protein has been shown to protect
      mice against cutaneous leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      tested the efficacy of a novel combination of established protective parasite
      antigens expressed by L. tarentolae together with a sand fly salivary antigen as
      a vaccine strategy against L. major infection. The immunogenicity and protective
      efficacy of different DNA/Live and Live/Live prime-boost vaccination modalities
      with live recombinant L. tarentolae stably expressing cysteine proteinases (type
      I and II, CPA/CPB) and PpSP15, an immunogenic salivary protein from Phlebotomus
      papatasi, a natural vector of L. major, were tested both in susceptible BALB/c
      and resistant C57BL/6 mice. Both humoral and cellular immune responses were
      assessed before challenge and at 3 and 10 weeks after Leishmania infection. In
      both strains of mice, the strongest protective effect was observed when priming
      with PpSP15 DNA and boosting with PpSP15 DNA and live recombinant L. tarentolae
      stably expressing cysteine proteinase genes. CONCLUSION/SIGNIFICANCE: The present
      study is the first to use a combination of recombinant L. tarentolae with a sand
      fly salivary antigen (PpSP15) and represents a novel promising vaccination
      approach against leishmaniasis.

PMID- 24675713
TI  - Irregular consumption of energy intake in meals is associated with a higher
      cardiometabolic risk in adults of a British birth cohort.
AB  - BACKGROUND/OBJECTIVES: A potential risk factor for cardiometabolic diseases is
      irregular or inconsistent eating, however, research on this topic is scarce. We
      aimed to study associations between irregular consumption of energy intake in
      meals and cardiometabolic risk factors. SUBJECT AND METHODS: Dietary intake data
      were derived from 5-day estimated diet diaries of 1768 participants of the
      National Survey of Health and Development. Energy intakes during predefined meals
      (breakfast, lunch, dinner, between meals) and daily totals were analyzed using a
      score for irregularity based on the deviation from the 5-day mean energy intake.
      Logistic regression models were used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs) for having the metabolic syndrome or one of its
      components. Models were adjusted for sex, physical activity, socioeconomic
      status, marital status and smoking. RESULTS: Irregularity scores of energy intake
      ranged from 0-160 and were highest for between meals. An increased risk of the
      metabolic syndrome was associated with more irregular energy intake during
      breakfast (OR=1.34 (0.99, 1.81); P trend=0.04) and between meals (OR=1.36 (1.01,
      1.85); P trend=0.04). Moreover, increased waist circumference was associated with
      irregular energy intake during breakfast (OR=1.90 (1.47, 2.45); P trend <0.01),
      evening meal (OR=1.36 (1.06, 1.75); P trend=0.02) and daily total (OR=1.34 (1.04,
      1.72); P trend=0.01). No significant associations were found for the other
      components of the metabolic syndrome. CONCLUSIONS: Individuals with a more
      irregular intake of energy, especially during breakfast and between meals,
      appeared to have an increased cardiometabolic risk.

PMID- 24675714
TI  - Weight loss maintenance in overweight subjects on ad libitum diets with high or
      low protein content and glycemic index: the DIOGENES trial 12-month results.
AB  - BACKGROUND: A high dietary protein (P) content and low glycemic index (LGI) have
      been suggested to be beneficial for weight management, but long-term studies are
      scarce. OBJECTIVE: The DIOGENES randomized clinical trial investigated the effect
      of P and GI on weight loss maintenance in overweight or obese adults in eight
      centers across Europe. This study reports the 1-year results in two of the
      centers that extended the intervention to 1 year. METHOD: After an 8-week low
      calorie diet (LCD), 256 adults (body mass index >27 kg m(-)(2)) were randomized
      to five ad libitum diets for 12 months: high P/LGI (HP/LGI), HP/high GI (HP/HGI),
      low P/LGI (LP/LGI), LP/HGI and a control diet. During the first 6 months, foods
      were provided for free through a shop system and during the whole 12-month
      period, subjects received guidance by a dietician. Primary outcome variable was
      the change in body weight over the 12-month intervention period. RESULTS: During
      the LCD period, subjects lost 11.2 (10.8, 12.0) kg (mean (95% confidence interval
      (CI))). Average weight regain over the 12-month intervention period was 3.9 (95%
      CI 3.0-4.8) kg. Subjects on the HP diets regained less weight than subjects on
      the LP diets. The difference in weight regain after 1 year was 2.0 (0.4, 3.6) kg
      (P=0.017) (completers analysis, N=139) or 2.8 (1.4, 4.1) kg (P<0.001) (intention
      to-treat analysis, N=256). No consistent effect of GI on weight regain was found.
      There were no clinically relevant differences in changes in cardiometabolic risk
      factors among diet groups. CONCLUSION: A higher protein content of an ad libitum
      diet improves weight loss maintenance in overweight and obese adults over 12
      months.

PMID- 24675715
TI  - Mapping of the circulating metabolome reveals alpha-ketoglutarate as a predictor
      of morbid obesity-associated non-alcoholic fatty liver disease.
AB  - BACKGROUND: Obesity severely affects human health, and the accompanying non
      alcoholic fatty liver disease (NAFLD) is associated with high morbidity and
      mortality. Rapid and non-invasive methods to detect this condition may
      substantially improve clinical care. METHODS: We used liquid and gas
      chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS)
      analysis in a non-targeted metabolomics approach on the plasma from morbidly
      obese patients undergoing bariatric surgery to gain a comprehensive measure of
      metabolite levels. On the basis of these findings, we developed a method (GC-QTOF
      MS) for the accurate quantification of plasma alpha-ketoglutarate to explore its
      potential as a novel biomarker for the detection of NAFLD. RESULTS: Plasma
      biochemical differences were observed between patients with and without NAFLD
      indicating that the accumulation of lipids in hepatocytes decreased beta
      oxidation energy production, reduced liver function and altered glucose
      metabolism. The results obtained from the plasma analysis suggest
      pathophysiological insights that link lipid and glucose disturbances with alpha
      ketoglutarate. Plasma alpha-ketoglutarate levels are significantly increased in
      obese patients compared with lean controls. Among obese patients, the measurement
      of this metabolite differentiates between those with or without NAFLD. Data from
      the liver were consistent with data from plasma. Clinical utility was assessed,
      and the results revealed that plasma alpha-ketoglutarate is a fair-to-good
      biomarker in patients (n=230). Other common laboratory liver tests used in
      routine application did not favourably compare. CONCLUSION: Plasma alpha
      ketoglutarate is superior to common liver function tests in obese patients as a
      surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate
      the search for a therapeutic approach, may decrease the need for liver biopsy and
      may be useful in the assessment of disease progression.

PMID- 24675716
TI  - Dying cells protect survivors from radiation-induced cell death in Drosophila.
AB  - We report a phenomenon wherein induction of cell death by a variety of means in
      wing imaginal discs of Drosophila larvae resulted in the activation of an anti
      apoptotic microRNA, bantam. Cells in the vicinity of dying cells also become
      harder to kill by ionizing radiation (IR)-induced apoptosis. Both ban activation
      and increased protection from IR required receptor tyrosine kinase Tie, which we
      identified in a genetic screen for modifiers of ban. tie mutants were
      hypersensitive to radiation, and radiation sensitivity of tie mutants was rescued
      by increased ban gene dosage. We propose that dying cells activate ban in
      surviving cells through Tie to make the latter cells harder to kill, thereby
      preserving tissues and ensuring organism survival. The protective effect we
      report differs from classical radiation bystander effect in which neighbors of
      irradiated cells become more prone to death. The protective effect also differs
      from the previously described effect of dying cells that results in proliferation
      of nearby cells in Drosophila larval discs. If conserved in mammals, a phenomenon
      in which dying cells make the rest harder to kill by IR could have implications
      for treatments that involve the sequential use of cytotoxic agents and radiation
      therapy. 

PMID- 24675717
TI  - Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal
      recovery following cardiac surgery.
AB  - BACKGROUND: Difficulties in prediction and early identification of (acute kidney
      injury) AKI have hindered the ability to develop preventive and therapeutic
      measures for this syndrome. We tested the hypothesis that a urine test measuring
      insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of
      metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key
      mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac
      surgery patients. METHODS: We studied 50 patients at high risk for AKI undergoing
      cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were
      analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was
      AKI as defined by international consensus criteria following surgery.
      Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal
      recovery from AKI prior to hospital discharge. RESULTS: 26 patients (52%)
      developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur
      until 1-3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7]
      rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in
      patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration
      achieved in the first 24 hours following surgery (composite time point)
      demonstrated an area under the receiver-operating characteristic curve of 0.84.
      Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The
      decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal
      recovery. CONCLUSIONS: Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and
      specific biomarker to predict AKI early after cardiac surgery and to predict
      renal recovery. CLINICAL TRIAL REGISTRATION INFORMATION: www.germanctr.de/, DRKS
      ID: DRKS00005062.

PMID- 24675719
TI  - Dormancy-related seed positional effect in two populations of an annual grass
      from locations of contrasting aridity.
AB  - In grasses, variation in seed size and dormancy often results from a seed's
      position within a dispersal unit. In this paper, I asked whether seed positional
      effect within a spikelet contributes to ecotypic differentiation between two
      populations of Avena sterilis having different species range position and
      associated aridity. I created experimental seed banks in which germination of
      seeds (florets) having different positions within a spikelet was examined over
      three years. In addition, two germination tests were conducted under controlled
      conditions. The two populations were found to have a short-living soil seed bank
      due to sequential germination of the florets. Although positional seed dormancy
      effect in A. sterilis does not appear to be a specific desert adaptation against
      unpredictability of rainfall events, this trait does contribute to ecotypic
      differentiation between desert and Mediterranean populations. Consistent with bet
      hedging buffering against rainfall unpredictability, germination fractions in the
      first year were higher in the Mediterranean than in the desert population, while
      seeds of the desert origin had stronger dormancy and more sequential germination
      of florets. 

PMID- 24675718
TI  - Modeling mutual exclusivity of cancer mutations.
AB  - In large collections of tumor samples, it has been observed that sets of genes
      that are commonly involved in the same cancer pathways tend not to occur mutated
      together in the same patient. Such gene sets form mutually exclusive patterns of
      gene alterations in cancer genomic data. Computational approaches that detect
      mutually exclusive gene sets, rank and test candidate alteration patterns by
      rewarding the number of samples the pattern covers and by punishing its impurity,
      i.e., additional alterations that violate strict mutual exclusivity. However, the
      extant approaches do not account for possible observation errors. In practice,
      false negatives and especially false positives can severely bias evaluation and
      ranking of alteration patterns. To address these limitations, we develop a fully
      probabilistic, generative model of mutual exclusivity, explicitly taking
      coverage, impurity, as well as error rates into account, and devise efficient
      algorithms for parameter estimation and pattern ranking. Based on this model, we
      derive a statistical test of mutual exclusivity by comparing its likelihood to
      the null model that assumes independent gene alterations. Using extensive
      simulations, the new test is shown to be more powerful than a permutation test
      applied previously. When applied to detect mutual exclusivity patterns in
      glioblastoma and in pan-cancer data from twelve tumor types, we identify several
      significant patterns that are biologically relevant, most of which would not be
      detected by previous approaches. Our statistical modeling framework of mutual
      exclusivity provides increased flexibility and power to detect cancer pathways
      from genomic alteration data in the presence of noise. A summary of this paper
      appears in the proceedings of the RECOMB 2014 conference, April 2-5. 

PMID- 24675721
TI  - Pneumonia--still a killer.

PMID- 24675720
TI  - Psychological and behavioral changes during confinement in a 520-day simulated
      interplanetary mission to mars.
AB  - Behavioral health risks are among the most serious and difficult to mitigate
      risks of confinement in space craft during long-duration space exploration
      missions. We report on behavioral and psychological reactions of a multinational
      crew of 6 healthy males confined in a 550 m(3) chamber for 520 days during the
      first Earth-based, high-fidelity simulated mission to Mars. Rest-activity of
      crewmembers was objectively measured throughout the mission with wrist-worn
      actigraphs. Once weekly throughout the mission crewmembers completed the Beck
      Depression Inventory-II (BDI-II), Profile of Moods State short form (POMS),
      conflict questionnaire, the Psychomotor Vigilance Test (PVT-B), and series of
      visual analogue scales on stress and fatigue. We observed substantial inter
      individual differences in the behavioral responses of crewmembers to the
      prolonged mission confinement and isolation. The crewmember with the highest
      average POMS total mood disturbance score throughout the mission also reported
      symptoms of depression in 93% of mission weeks, which reached mild-to-moderate
      levels in >10% of mission weeks. Conflicts with mission control were reported
      five times more often than conflicts among crewmembers. Two crewmembers who had
      the highest ratings of stress and physical exhaustion accounted for 85% of the
      perceived conflicts. One of them developed a persistent sleep onset insomnia with
      ratings of poor sleep quality, which resulted in chronic partial sleep
      deprivation, elevated ratings of daytime tiredness, and frequent deficits in
      behavioral alertness. Sleep-wake timing was altered in two other crewmembers,
      beginning in the first few months of the mission and persisting throughout. Two
      crewmembers showed neither behavioral disturbances nor reports of psychological
      distress during the 17-month period of mission confinement. These results
      highlight the importance of identifying behavioral, psychological, and biological
      markers of characteristics that predispose prospective crewmembers to both
      effective and ineffective behavioral reactions during the confinement of
      prolonged spaceflight, to inform crew selection, training, and individualized
      countermeasures.

PMID- 24675723
TI  - Macrophage migration inhibitory factor in myocardial ischaemia/reperfusion
      injury.
AB  - Acute myocardial infarction (AMI) remains one of the leading causes of death in
      the developed world. There is emerging evidence that the cytokine macrophage
      migration inhibitory factor (MIF) is a crucial player in AMI. Cardioprotection by
      MIF is likely to be a multifactorial phenomenon mediated by receptor-mediated
      signalling processes, intracellular protein-protein interactions, and enzymatic
      redox regulation. Co-ordinating several pathways in the ischaemic heart, MIF
      contributes to receptor-mediated regulation of cardioprotective AMP-activated
      protein kinase signalling, inhibition of pro-apoptotic cascades, and the
      reduction of oxidative stress in the post-ischaemic heart. Moreover, the
      cardioprotective properties of MIF are modulated by S-nitros(yl)ation. These
      effects in the pathophysiology of myocardial ischaemia/reperfusion injury qualify
      MIF as a promising therapeutic target in the future. We here summarize the
      findings of experimental and clinical studies and emphasize the therapeutic
      potential of MIF in AMI. 

PMID- 24675722
TI  - Cardioprotective function of cardiac macrophages.
AB  - The heart is composed of several cell types including cardiomyocytes, cardiac
      fibroblasts, endothelial, and smooth muscle cells. In addition to these major
      cell types, cardiac macrophages are also present in small numbers under
      physiological conditions. Recently, the resident macrophage is considered to have
      vital functions in the maintenance of tissues and homeostasis in many organs,
      including brain, liver, adipose tissue, lymphatic tissue, and intestinal tract.
      However, detailed functions of the cardiac resident macrophage are not fully
      understood. Although the removal of debris arising from damaged cardiomyocytes
      and pro-inflammatory effects after heart injuries are conventional tasks of
      cardiac macrophages (classically activated macrophage or M1 macrophage), novel
      functions like anti-inflammatory roles, adaptive response, and tissue maintenance
      have also been reported in recent years. Macrophages that possess these novel
      functions are generally so-called M2 macrophages, which are alternatively
      activated and show anti-inflammatory phenotype under pathological conditions. In
      this review, we focus on the cardioprotective function of the cardiac macrophage
      and discuss in light of unveiled fundamental functions of macrophages that have
      been also found in other organs. 

PMID- 24675725
TI  - The behavior of f-levels in hcp and bcc rare-earth elements in the ground state
      and XPS and BIS spectroscopy from density-functional theory.
AB  - The electronic structures of rare-earth elements in the hexagonal close-packed
      structure and Europium in the body-centered cubic structure are calculated using
      density-functional theory (DFT). X-ray photoemission spectroscopy (XPS) and
      bremsstrahlung isochromatic spectroscopy (BIS) simulations are made within DFT by
      implying that the f-electrons are excited by a large photon energy, either by
      removal from the occupied states in XPS or by addition to the unoccupied f-states
      in BIS. The results show sizable differences in the apparent position of the f
      states compared to the f-band energy of the ground states. This result is
      fundamentally different from calculations assuming strong on-site correlation,
      since all the calculations are based on DFT. The spin-orbit coupling and
      multiplet splittings are not included, and the present simulation accounts for
      almost half of the difference between the f-level positions in the DFT ground
      states and the observed f-level positions. The electronic specific-heat at low T
      is compatible with the DFT ground state, where f-electrons often reside at the
      Fermi level. 

PMID- 24675724
TI  - Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in
      atherogenesis.
AB  - AIM: MicroRNAs (miRNAs) play key roles in inflammatory responses of macrophages.
      However, the function of miRNAs in macrophage-derived foam cell formation is
      unclear. Here, we investigated the role of miRNAs in macrophage-derived foam cell
      formation and atherosclerotic development. METHODS AND RESULTS: Using
      quantitative reverse transcription-PCR (qRT-PCR), we found that the level of miR
      155 expression was increased significantly in both plasma and macrophages from
      atherosclerosis (ApoE(-/-)) mice. We identified that oxidized low density
      lipoprotein (oxLDL) induced the expression and release of miR-155 in macrophages,
      and that miR-155 was required to mediate oxLDL-induced lipid uptake and reactive
      oxygen species (ROS) production of macrophages. Furthermore, ectopic
      overexpression and knockdown experiments identified that HMG box-transcription
      protein1 (HBP1) is a novel target of miR-155. Knockdown of HBP1 enhanced lipid
      uptake and ROS production in oxLDL-stimulated macrophages, and overexpression of
      HBP1 repressed these effects. Furthermore, bioinformatics analysis identified
      three YY1 binding sites in the promoter region of pri-miR-155 and verified YY1
      binding directly to its promoter region. Detailed analysis showed that the
      YY1/HDAC2/4 complex negatively regulated the expression of miR-155 to suppress
      oxLDL-induced foam cell formation. Importantly, inhibition of miR-155 by a
      systemically delivered antagomiR-155 decreased clearly lipid-loading in
      macrophages and reduced atherosclerotic plaques in ApoE(-/-) mice. Moreover, we
      observed that the level of miR-155 expression was up-regulated in CD14(+)
      monocytes from patients with coronary heart disease. CONCLUSION: Our findings
      reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived
      foam cell formation during early atherogenesis and suggest that miR-155 is a
      potential therapeutic target for atherosclerosis.

PMID- 24675727
TI  - Green light synergistally enhances male sweetpotato weevil response to sex
      pheromone.
AB  - Sweetpotato, commercially grown in over 100 countries, is one of the ten most
      important staple crops in the world. Sweetpotato weevil is a major pest of
      sweetpotato in most areas of cultivation, the feeding of which induces production
      in the sweetpotato root of extremely bitter tasting and toxic sesquiterpenes
      which can render the sweetpotato unfit for consumption. A significant step
      towards improved management of this weevil species was the identification of a
      female-produced sex pheromone [(Z)-3-dodecenyl (E)-2-butenoate] to which males
      are highly attracted. Reported here are results of research that documents a
      nearly 5-fold increase in male sweetpotato weevil catch in traps baited with this
      pheromone and a green light provided by a solar-powered, light-emitting diode
      (LED). The combination of olfactory and night-visible visual cues significantly
      enhanced trap effectiveness for this nighttime-active insect species. These
      results provide promise for improved sweetpotato weevil detection and suppression
      in mass trapping programs. 

PMID- 24675726
TI  - The Geogenomic Mutational Atlas of Pathogens (GoMAP) web system.
AB  - We present a new approach for pathogen surveillance we call Geogenomics.
      Geogenomics examines the geographic distribution of the genomes of pathogens,
      with a particular emphasis on those mutations that give rise to drug resistance.
      We engineered a new web system called Geogenomic Mutational Atlas of Pathogens
      (GoMAP) that enables investigation of the global distribution of individual drug
      resistance mutations. As a test case we examined mutations associated with HIV
      resistance to FDA-approved antiretroviral drugs. GoMAP-HIV makes use of existing
      public drug resistance and HIV protein sequence data to examine the distribution
      of 872 drug resistance mutations in ~ 502,000 sequences for many countries in the
      world. We also implemented a broadened classification scheme for HIV drug
      resistance mutations. Several patterns for geographic distributions of resistance
      mutations were identified by visual mining using this web tool. GoMAP-HIV is an
      open access web application available at http://www.bio
      toolkit.com/GoMap/project/

PMID- 24675729
TI  - Flux and reflux: metabolite reflux in plant suspension cells and its implications
      for isotope-assisted metabolic flux analysis.
AB  - Isotope-assisted metabolic flux analysis (MFA) is a powerful methodology to
      quantify intracellular fluxes via isotope labeling experiments (ILEs). In batch
      cultures, which are often convenient, inexpensive or inevitable especially for
      eukaryotic systems, MFA is complicated by the presence of the initially present
      biomass. This unlabeled biomass may either mix with the newly synthesized labeled
      biomass or reflux into the metabolic network, thus masking the true labeling
      patterns in the newly synthesized biomass. Here, we report a detailed
      investigation of such metabolite reflux in cell suspensions of the tree poplar.
      In ILEs supplying 28% or 98% U-(13)C glucose as the sole organic carbon source,
      biomass components exhibited lower (13)C enrichments than the supplied glucose as
      well as anomalous isotopomers not explainable by simple mixing of the initial and
      newly synthesized biomass. These anomalous labeling patterns were most prominent
      in a 98% U-(13)C glucose ILE. By comparing the performance of light- and dark
      grown cells as well as by analyzing the isotope labeling patterns in aspartic and
      glutamic acids, we eliminated photosynthetic or anaplerotic fixation of
      extracellular (12)CO2 as explanations for the anomalous labeling patterns. We
      further investigated four different metabolic models for interpreting the
      labeling patterns and evaluating fluxes: (i) a carbon source (glucose) dilution
      model, (ii) an isotopomer correction model with uniform dilution for all amino
      acids, (iii) an isotopomer correction model with variable dilution for different
      amino acids, and (iv) a comprehensive metabolite reflux model. Of these, the
      metabolite reflux model provided a substantially better fit for the observed
      labeling patterns (sum of squared residues: 538) than the other three models
      whose sum of squared residues were (i) 4626, (ii) 4983, and (iii) 1748,
      respectively. We compared fluxes determined using the metabolite reflux model to
      those determined using an independent methodology involving an excessively long
      ILE to wash out initial biomass and a minimal reflux model. This comparison
      showed identical or similar distributions for a majority of fluxes, thus
      validating our comprehensive reflux model. In summary, we have demonstrated the
      need for quantifying interactions between initially present biomass and newly
      synthesized biomass in batch ILEs, especially through the use of ~100% U-(13)C
      carbon sources. Our ILEs reveal a high amount of metabolite reflux in poplar cell
      suspensions, which is well explained by a comprehensive metabolite reflux model. 

PMID- 24675730
TI  - CAGExploreR: an R package for the analysis and visualization of promoter dynamics
      across multiple experiments.
AB  - : Alternate promoter usage is an important molecular mechanism for generating RNA
      and protein diversity. Cap Analysis Gene Expression (CAGE) is a powerful approach
      for revealing the multiplicity of transcription start site (TSS) events across
      experiments and conditions. An understanding of the dynamics of TSS choice across
      these conditions requires both sensitive quantification and comparative
      visualization. We have developed CAGExploreR, an R package to detect and
      visualize changes in the use of specific TSS in wider promoter regions in the
      context of changes in overall gene expression when comparing different CAGE
      samples. These changes provide insight into the modification of transcript
      isoform generation and regulatory network alterations associated with cell types
      and conditions. CAGExploreR is based on the FANTOM5 and MPromDb promoter set
      definitions but can also work with user-supplied regions. The package compares
      multiple CAGE libraries simultaneously. Supplementary Materials describe methods
      in detail, and a vignette demonstrates a workflow with a real data example.
      AVAILABILITY AND IMPLEMENTATION: The package is freely available under the MIT
      license from CRAN (http://cran.r-project.org/web/packages/CAGExploreR). CONTACT:
      edimont@mail.harvard.edu Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 24675728
TI  - Vibrio vulnificus MO6-24/O lipopolysaccharide stimulates superoxide anion,
      thromboxane B2, matrix metalloproteinase-9, cytokine and chemokine release by rat
      brain microglia in vitro.
AB  - Although human exposure to Gram-negative Vibrio vulnificus (V. vulnificus)
      lipopolysaccharide (LPS) has been reported to result in septic shock, its impact
      on the central nervous system's innate immunity remains undetermined. The purpose
      of this study was to determine whether V. vulnificus MO6-24/O LPS might activate
      rat microglia in vitro and stimulate the release of superoxide anion (O2-), a
      reactive oxygen species known to cause oxidative stress and neuronal injury in
      vivo. Brain microglia were isolated from neonatal rats, and then treated with
      either V. vulnificus MO6-24/O LPS or Escherichia coli O26:B6 LPS for 17 hours in
      vitro. O2- was determined by cytochrome C reduction, and matrix metalloproteinase
      2 (MMP-2) and MMP-9 by gelatinase zymography. Generation of cytokines tumor
      necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), IL-6, and
      transforming growth factor-beta 1 (TGF-beta1), chemokines macrophage inflammatory
      protein (MIP-1alpha)/chemokine (C-C motif) ligand 3 (CCL3), MIP-2/chemokine (C-X
      C motif) ligand 2 (CXCL2), monocyte chemotactic protein-1 (MCP-1)/CCL2, and
      cytokine-induced neutrophil chemoattractant-2alpha/beta (CINC-2alpha/beta)/CXCL3,
      and brain-derived neurotrophic factor (BDNF), were determined by specific
      immunoassays. Priming of rat microglia by V. vulnificus MO6-24/O LPS in vitro
      yielded a bell-shaped dose-response curve for PMA (phorbol 12-myristate 13
      acetate)-stimulated O2- generation: (1) 0.1-1 ng/mL V. vulnificus LPS enhanced O2
      generation significantly but with limited inflammatory mediator generation; (2)
      10-100 ng/mL V. vulnificus LPS maximized O2- generation with concomitant release
      of thromboxane B2 (TXB2), matrix metalloproteinase-9 (MMP-9), and several
      cytokines and chemokines; (3) 1000-100,000 ng/mL V. vulnificus LPS, with the
      exception of TXB2, yielded both attenuated O2- production, and a progressive
      decrease in MMP-9, cytokines and chemokines investigated. Thus concentration
      dependent treatment of neonatal brain microglia with V. vulnificus MO6-24/O LPS
      resulted in a significant rise in O2- production, followed by a progressive
      decrease in O2- release, with concomitant release of lactic dehydrogenase (LDH),
      and generation of TXB2, MMP-9, cytokines and chemokines. We hypothesize that the
      inflammatory mediators investigated may be cytotoxic to microglia in vitro, by an
      as yet undetermined autocrine mechanism. Although V. vulnificus LPS was less
      potent than E. coli LPS in vitro, inflammatory mediator release by the former was
      clearly more efficacious. Finally, we hypothesize that should V. vulnificus LPS
      gain entry into the CNS, it would be possible that microglia might become
      activated, resulting in high levels of O2- as well as neuroinflammatory TXB2, MMP
      9, cytokines and chemokines.

PMID- 24675731
TI  - Central inflammation and leptin resistance are attenuated by ginsenoside Rb1
      treatment in obese mice fed a high-fat diet.
AB  - A low-grade pro-inflammatory state is at the pathogenic core of obesity and type
      2 diabetes. We tested the hypothesis that the plant terpenoid compound
      ginsenoside Rb1 (Rb1), known to exert anti-inflammatory effects, would ameliorate
      obesity, obesity-associated inflammation and glucose intolerance in the high-fat
      diet-induced obese mouse model. Furthermore, we examined the effect of Rb1
      treatment on central leptin sensitivity and the leptin signaling pathway in the
      hypothalamus. We found that intraperitoneal injections of Rb1 (14 mg/kg, daily)
      for 21 days significantly reduced body weight gain, fat mass accumulation, and
      improved glucose tolerance in obese mice on a HF diet compared to vehicle
      treatment. Importantly, Rb1 treatment also reduced levels of pro-inflammatory
      cytokines (TNF-alpha, IL-6 and/or IL-1beta) and NF-kappaB pathway molecules (p
      IKK and p-IkappaBalpha) in adipose tissue and liver. In the hypothalamus, Rb1
      treatment decreased the expression of inflammatory markers (IL-6, IL-1beta and p
      IKK) and negative regulators of leptin signaling (SOCS3 and PTP1B). Furthermore,
      Rb1 treatment also restored the anorexic effect of leptin in high-fat fed mice as
      well as leptin pSTAT3 signaling in the hypothalamus. Ginsenoside Rb1 has
      potential for use as an anti-obesity therapeutic agent that modulates obesity
      induced inflammation and improves central leptin sensitivity in HF diet-induced
      obesity. 

PMID- 24675733
TI  - Directed differentiation of embryonic origin-specific vascular smooth muscle
      subtypes from human pluripotent stem cells.
AB  - Vascular smooth muscle cells (SMCs) arise from diverse developmental origins.
      Regional distribution of vascular diseases may, in part, be attributed to this
      inherent heterogeneity in SMC lineage. Therefore, systems for generating human
      SMC subtypes of distinct embryonic origins would represent useful platforms for
      studying the influence of SMC lineage on the spatial specificity of vascular
      disease. Here we describe how human pluripotent stem cells can be differentiated
      into distinct populations of SMC subtypes under chemically defined conditions.
      The initial stage (days 0-5 or 0-7) begins with the induction of three
      intermediate lineages: neuroectoderm, lateral plate mesoderm and paraxial
      mesoderm. Subsequently, these precursor lineages are differentiated into
      contractile SMCs (days 5-19+). At key stages, the emergence of lineage-specific
      markers confirms recapitulation of embryonic developmental pathways and
      generation of functionally distinct SMC subtypes. The ability to derive an
      unlimited supply of human SMCs will accelerate applications in regenerative
      medicine and disease modeling. 

PMID- 24675736
TI  - Detailed mass analysis of structural heterogeneity in monoclonal antibodies using
      native mass spectrometry.
AB  - The molecular complexity of biopharmaceuticals puts severe demands on the
      bioanalytical techniques required for their comprehensive structural
      characterization. Mass spectrometry (MS) has gained importance in the analysis of
      biopharmaceuticals, taking different complementary approaches ranging from
      peptide-based sequencing to direct analysis of intact proteins and protein
      assemblies. In this protocol, we describe procedures optimized to perform the
      analysis of monoclonal antibodies (mAbs) at the intact protein level under pseudo
      native conditions, using native MS. Some of the strengths of native MS in the
      analysis of biopharmaceuticals are its analysis speed, sensitivity and
      specificity: for most experiments, the whole protocol requires one working day,
      whereby tens of samples can be analyzed in a multiplexed manner, making it
      suitable for high-throughput analysis. This method can be used for different
      applications such as the analysis of mixtures of mAbs, drug-antibody conjugates
      and the analysis of mAb post-translational modifications, including the
      qualitative and quantitative analysis of mAb glycosylation. 

PMID- 24675734
TI  - Epitope-tagged protein-based artificial miRNA screens for optimized gene
      silencing in plants.
AB  - Artificial miRNA (amiRNA) technology offers highly specific gene silencing in
      diverse plant species. The principal challenge in amiRNA application is to select
      potent amiRNAs from hundreds of bioinformatically designed candidates to enable
      maximal target gene silencing at the protein level. To address this issue, we
      developed the epitope-tagged protein-based amiRNA (ETPamir) screens, in which
      single or multiple potential target genes encoding epitope-tagged proteins are
      constitutively or inducibly coexpressed with individual amiRNA candidates in
      plant protoplasts. Accumulation of tagged proteins, detected by immunoblotting
      with commercial tag antibodies, inversely and quantitatively reflects amiRNA
      efficacy in vivo. The core procedure, from protoplast isolation to identification
      of optimal amiRNA, can be completed in 2-3 d. The ETPamir screens circumvent the
      limited availability of plant antibodies and the complexity of plant amiRNA
      silencing at target mRNA and/or protein levels. The method can be extended to
      verify predicted target genes for endogenous plant miRNAs. 

PMID- 24675735
TI  - Antigen-specific activation and cytokine-facilitated expansion of naive, human
      CD8+ T cells.
AB  - Antigen-specific priming of human, naive T cells has been difficult to assess.
      Owing to the low initial frequency in the naive cell pool of specific T cell
      precursors, such an analysis has been obscured by the requirements for repeated
      stimulations and prolonged culture time. In this protocol, we describe how to
      evaluate antigen-specific priming of CD8(+) cells 10 d after a single specific
      stimulation. The assay provides reference conditions, which result in the
      expansion of a substantial population of antigen-specific T cells from the naive
      repertoire. Various conditions and modifications during the priming process
      (e.g., testing new cytokines, co-stimulators and so on) can now be directly
      compared with the reference conditions. Factors relevant to achieving effective
      priming include the dendritic cell preparation, the T cell preparation, the cell
      ratio at the time of priming, the serum source used for the experiment and the
      timing of addition and concentration of the cytokines used for expansion. This
      protocol is relevant for human immunology, vaccine biology and drug development. 

PMID- 24675737
TI  - Variable gelation time and stiffness of low-molecular-weight hydrogels through
      catalytic control over self-assembly.
AB  - This protocol details the preparation of low-molecular-weight hydrogels (LMWGs)
      in which the gelation time and mechanical stiffness of the final gel can be tuned
      with the concentration of the catalyst used in the in situ formation of the
      hydrogelator. By altering the rate of formation of the hydrazone-based gelator
      from two water-soluble compounds--an oligoethylene functionalized benzaldehyde
      and a cyclohexane-derived trishydrazide--in the presence of acid or aniline as
      catalyst, the kinetics of gelation can be tuned from hours to minutes. The
      resulting materials display controllable stiffness in the 5-50 kPa range. This
      protocol works at ambient temperatures in water, at either neutral or moderately
      acidic pH (phosphate buffer, pH 5) depending on the catalyst used. The hydrazide
      and aldehyde precursors take a total of 5 d to prepare. The final gel is prepared
      by mixing aqueous solutions of the two precursors and can take between minutes
      and hours to set, depending on the catalytic conditions. We also describe
      analysis of the hydrogels by critical gel concentration (CGC) tests, rheology and
      confocal laser-scanning microscopy (CLSM).

PMID- 24675738
TI  - Identification of parasitic communities within European ticks using next
      generation sequencing.
AB  - BACKGROUND: Risk assessment of tick-borne and zoonotic disease emergence
      necessitates sound knowledge of the particular microorganisms circulating within
      the communities of these major vectors. Assessment of pathogens carried by wild
      ticks must be performed without a priori, to allow for the detection of new or
      unexpected agents. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the potential of
      Next-Generation Sequencing techniques (NGS) to produce an inventory of parasites
      carried by questing ticks. Sequences corresponding to parasites from two distinct
      genera were recovered in Ixodes ricinus ticks collected in Eastern France:
      Babesia spp. and Theileria spp. Four Babesia species were identified, three of
      which were zoonotic: B. divergens, Babesia sp. EU1 and B. microti; and one which
      infects cattle, B. major. This is the first time that these last two species have
      been identified in France. This approach also identified new sequences
      corresponding to as-yet unknown organisms similar to tropical Theileria species.
      CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the capability of NGS to
      produce an inventory of live tick-borne parasites, which could potentially be
      transmitted by the ticks, and uncovers unexpected parasites in Western Europe.

PMID- 24675739
TI  - Human dignity in religion-embedded cross-cultural nursing.
AB  - BACKGROUND: Although human dignity is an unconditional value of every human
      being, it can be shattered by extrinsic factors. It is necessary to discover the
      authentic meaning of patients' dignity preservation from different religious
      perspectives to provide professional cross-cultural care in a diverse setting.
      RESEARCH OBJECTIVE: This article identifies common experiences of Iranian Muslim
      and Armenian Christian patients regarding dignified care at the bedside. RESEARCH
      DESIGN: This is a qualitative study of participants' experiences of dignified
      care elicited by individual in-depth semi-structured interviews. PARTICIPANTS AND
      RESEARCH CONTEXT: A purposeful sample of 10 participants (five Iranian Muslims
      and five Iranian Armenians) from various private and governmental hospital
      settings was chosen. ETHICAL CONSIDERATIONS: This study was approved by the
      ethics committee of Tehran University of Medical Sciences. All the participants
      were provided with information about the purpose and the nature of the study, the
      voluntary condition of their participation in this study, and the anonymous
      reporting of recorded interviews. FINDINGS: The common experiences of Christian
      and Muslim patients regarding dignity preservation emerged as "exigency of
      respecting human nobility" and "providing person-centered care." DISCUSSION AND
      CONCLUSION: It is essential to recognize the humanness and individuality of each
      patient to preserve and promote human dignity in diverse cross-cultural settings.
      The findings support and expand current understanding about the objective and
      subjective nature of dignity preservation in cross-cultural nursing.

PMID- 24675740
TI  - Genetic diversity in the interference selection limit.
AB  - Pervasive natural selection can strongly influence observed patterns of genetic
      variation, but these effects remain poorly understood when multiple selected
      variants segregate in nearby regions of the genome. Classical population genetics
      fails to account for interference between linked mutations, which grows
      increasingly severe as the density of selected polymorphisms increases. Here, we
      describe a simple limit that emerges when interference is common, in which the
      fitness effects of individual mutations play a relatively minor role. Instead,
      similar to models of quantitative genetics, molecular evolution is determined by
      the variance in fitness within the population, defined over an effectively
      asexual segment of the genome (a "linkage block"). We exploit this insensitivity
      in a new "coarse-grained" coalescent framework, which approximates the effects of
      many weakly selected mutations with a smaller number of strongly selected
      mutations that create the same variance in fitness. This approximation generates
      accurate and efficient predictions for silent site variability when interference
      is common. However, these results suggest that there is reduced power to resolve
      individual selection pressures when interference is sufficiently widespread,
      since a broad range of parameters possess nearly identical patterns of silent
      site variability. 

PMID- 24675741
TI  - Roles of raft-anchored adaptor Cbp/PAG1 in spatial regulation of c-Src kinase.
AB  - The tyrosine kinase c-Src is upregulated in numerous human cancers, implying a
      role for c-Src in cancer progression. Previously, we have shown that
      sequestration of activated c-Src into lipid rafts via a transmembrane adaptor,
      Cbp/PAG1, efficiently suppresses c-Src-induced cell transformation in Csk
      deficient cells, suggesting that the transforming activity of c-Src is spatially
      regulated via Cbp in lipid rafts. To dissect the molecular mechanisms of the Cbp
      mediated regulation of c-Src, a combined analysis was performed that included
      mathematical modeling and in vitro experiments in a c-Src- or Cbp-inducible
      system. c-Src activity was first determined as a function of c-Src or Cbp levels,
      using focal adhesion kinase (FAK) as a crucial c-Src substrate. Based on these
      experimental data, two mathematical models were constructed, the sequestration
      model and the ternary model. The computational analysis showed that both models
      supported our proposal that raft localization of Cbp is crucial for the
      suppression of c-Src function, but the ternary model, which includes a ternary
      complex consisting of Cbp, c-Src, and FAK, also predicted that c-Src function is
      dependent on the lipid-raft volume. Experimental analysis revealed that c-Src
      activity is elevated when lipid rafts are disrupted and the ternary complex forms
      in non-raft membranes, indicating that the ternary model accurately represents
      the system. Moreover, the ternary model predicted that, if Cbp enhances the
      interaction between c-Src and FAK, Cbp could promote c-Src function when lipid
      rafts are disrupted. These findings underscore the crucial role of lipid rafts in
      the Cbp-mediated negative regulation of c-Src-transforming activity, and explain
      the positive role of Cbp in c-Src regulation under particular conditions where
      lipid rafts are perturbed. 

PMID- 24675743
TI  - Critical level statistics for weakly disordered graphene.
AB  - In two dimensions chaotic level statistics with the Wigner spacing distribution
      P(S) is expected for massless fermions in the Dirac region. The obtained P(S) for
      weakly disordered finite graphene samples with zigzag edges turns out, however,
      to be neither chaotic (Wigner) nor localized (Poisson). It is similar to the
      intermediate statistics at the critical point of the Anderson metal-insulator
      transition. The quantum transport of finite graphene for weak disorder, with
      critical level statistics can occur via edge states as in topological insulators,
      and for strong disorder, graphene behaves as an ordinary Anderson insulator with
      Poisson statistics. 

PMID- 24675742
TI  - Ten simple rules for effective computational research.

PMID- 24675745
TI  - Quality of care in one Italian nursing home measured by ACOVE process indicators.
AB  - OBJECTIVES: To adapt the Assessing Care of Vulnerable Elders Quality Indicators
      (ACOVE QIs) for use in Italy, to assess the adherence to these indicators as
      reported in the medical records of residents in a nursing home (NH), to compare
      this adherence for general medical and geriatric conditions, and eventually, to
      identify the relationships between patients' characteristics and reported
      processes of care. METHODS: Two physicians collected the data by reviewing
      medical records of all NH residents in the previous 5 years, for a period of one
      year. Patients aged <65 years were excluded. A total of 245 patients were
      reviewed during the study period. The ACOVE QIs set, developed for NH processes
      of care, was used to assess the quality of care. Multivariate analysis was
      performed to identify and to assess the role of patients' characteristics on
      quality of processes of care by several domains of care in general medical and
      geriatric conditions. RESULTS: With the exception of diabetes management, quality
      of processes of care for general medical conditions approached adequate
      adherence. Care falls substantially short of acceptable levels for geriatric
      conditions (pressure ulcers, falls, dementia). On the contrary, the recommended
      interventions for urinary incontinence were commonly performed. Adherence to
      indicators varied for the different domains of care and was proven worse for the
      screening and prevention indicators both for geriatric and general medical
      conditions. Statistical analysis showed disparities in provision of appropriate
      processes of care associated with gender, age, co-morbidities, level of function
      and mobility, length of stay and modality of discharge by NHs. CONCLUSIONS:
      Adherence to recommended processes of care delivered in NH is inadequate.
      Substantial work lies ahead for the improvement of care. Efforts should focus
      particularly on management of geriatric conditions and on preventive healthcare.

PMID- 24675744
TI  - A cytosolic chaperone complexes with dynamic membrane J-proteins and mobilizes a
      nonenveloped virus out of the endoplasmic reticulum.
AB  - Nonenveloped viruses undergo conformational changes that enable them to bind to,
      disrupt, and penetrate a biological membrane leading to successful infection. We
      assessed whether cytosolic factors play any role in the endoplasmic reticulum
      (ER) membrane penetration of the nonenveloped SV40. We find the cytosolic SGTA
      Hsc70 complex interacts with the ER transmembrane J-proteins DnaJB14 (B14) and
      DnaJB12 (B12), two cellular factors previously implicated in SV40 infection. SGTA
      binds directly to SV40 and completes ER membrane penetration. During ER-to
      cytosol transport of SV40, SGTA disengages from B14 and B12. Concomitant with
      this, SV40 triggers B14 and B12 to reorganize into discrete foci within the ER
      membrane. B14 must retain its ability to form foci and interact with SGTA-Hsc70
      to promote SV40 infection. Our results identify a novel role for a cytosolic
      chaperone in the membrane penetration of a nonenveloped virus and raise the
      possibility that the SV40-induced foci represent cytosol entry sites. 

PMID- 24675746
TI  - Identification and analysis of differential miRNAs in PK-15 cells after foot-and
      mouth disease virus infection.
AB  - The alterations of MicroRNAs(miRNAs) in host cell after foot-and-mouth disease
      virus (FMDV) infection is still obscure. To increase our understanding of the
      pathogenesis of FMDV at the post-transcriptional regulation level, Solexa high
      throu MicroRNAs (miRNAs) play an important role both in the post-transcriptional
      regulation of gene expression and host-virus interactions. Despite investigations
      of miRNA expression ghput sequencing and bioinformatic tools were used to
      identify differentially expressed miRNAs and analyze their functions during FMDV
      infection of PK-15 cells. Results indicated that 9,165,674 and 9,230,378 clean
      reads were obtained, with 172 known and 72 novel miRNAs differently expressed in
      infected and uninfected groups respectively. Some of differently expressed miRNAs
      were validated using stem-loop real-time quantitative RT-PCR. The GO annotation
      and KEGG pathway analysis for target genes revealed that differently expressed
      miRNAs were involved in immune response and cell death pathways.

PMID- 24675747
TI  - Mild parkinsonian signs in the elderly--is there an association with PD?
      Crossectional findings in 992 individuals.
AB  - BACKGROUND: Mild parkinsonian signs (MPS) are common in the elderly population,
      and have been associated with vascular diseases, mild cognitive impairment and
      dementia; however their relation to Parkinson's disease (PD) is unclear.
      Hypothesizing that individuals with MPS may reflect a pre-stage of PD, i.e. a
      stage in which the nigrostriatal system is already affected although to a milder
      degree than at the time of PD diagnosis, aim of this study was to evaluate the
      similarities between MPS and PD. METHODS: The TREND study is a prospective cross
      sectional cohort study in individuals >50 years with biennial assessments
      designed to identify markers for an earlier diagnosis of Parkinson's and
      Alzheimer's disease. For this substudy 992 individuals were included for analyses
      (892 controls, 73 MPS individuals, 27 PD patients). Parameters defining risk of
      PD (sex, age, positive family history), prodromal markers (hyposmia, REM sleep
      behavior disorder, depression and autonomic failure) as well as quantitative fine
      motor, axial motor and cognitive parameters were compared between the three
      cohorts. RESULTS: As expected, PD patients differed from controls with regard to
      12 of 15 of the assessed parameters. MPS individuals differed significantly from
      controls in 12 of the PD-associated parameters, but differed from PD only in 5
      parameters. CONCLUSION: This study shows that individuals with MPS share many
      prodromal and clinical markers of PD with PD patients, implying that either a
      common dynamic process or similar constitutional factors occur in MPS individuals
      and PD patients.

PMID- 24675748
TI  - Identification of 17 HrpX-regulated proteins including two novel type III
      effectors, XOC_3956 and XOC_1550, in Xanthomonas oryzae pv. oryzicola.
AB  - The function of some hypothetical proteins, possibly regulated by key hrp
      regulators, in the pathogenicity of phytopathogenic bacteria remains largely
      unknown. In the present study, in silicon microarray data demonstrated that the
      expression of 17 HrpX-regulated protein (Xrp) genes of X. oryzae pv. oryzicola
      (Xoc), which causes bacterial leaf streak in rice, were either positively or
      negatively regulated by HrpX or/and HrpG. Bioinformatics analysis demonstrated
      that five Xrps possess a putative type III secretion (T3S) signal in the first 50
      N-terminal amino acids, six xrp genes contain a PIP-box-like sequence (TTCGB-NX
      TTCGB, 9 <= X <= 25) in the promoter regions, and two Xrps have both motifs.
      Twelve Xrps are widely conserved in Xanthomonas spp., whereas four are specific
      for X. oryzae (Xrp6) or Xoc (Xrp8, Xrp14 and Xrp17). In addition to the
      regulation by HrpG/HrpX, some of the 17 genes were also modulated by another hrp
      regulator HrpD6. Mutagenesis of these 17 genes indicated that five Xrps (Xrp1,
      Xrp2, Xrp5, Xrp8 and Xrp14) were required for full virulence and bacterial growth
      in planta. Immunoblotting assays and fusion with N-terminally truncated AvrXa10
      indicated that Xrp3 and Xrp5 were secreted and translocated into rice cells
      through the type-III secretion system (T3S), suggesting they are novel T3S
      effectors. Our results suggest that Xoc exploits an orchestra of proteins that
      are regulated by HrpG, HrpX and HrpD6, and these proteins facilitate both
      infection and metabolism.

PMID- 24675750
TI  - Intramedullary nailing of tibial shaft fractures distal to total knee
      arthroplasty.
AB  - Tibial shaft fractures distal to total knee arthroplasty are rare, but they are
      likely to become more common with the increasing number of arthroplasty
      procedures being performed. These fracture patterns have been treated in the past
      either with closed reduction and casting/bracing or with open reduction internal
      fixation using plates. Weight-bearing precautions in the elderly patient
      population can affect patient disposition, and weight bearing on extramedullary
      fixation can lead to early hardware failure. We present a series of nailing
      techniques that can be used for tibial fractures distal to a well-fixed total
      knee arthroplasty that avoids the tibial baseplate, provides stable fracture
      fixation, and allows for early weight bearing.

PMID- 24675749
TI  - The tomato leucine-rich repeat receptor-like kinases SlSERK3A and SlSERK3B have
      overlapping functions in bacterial and nematode innate immunity.
AB  - The Somatic Embryogenesis Receptor Kinase 3 (SERK3)/Brassinosteroid (BR)
      Insensitive 1-Associated Kinase 1 (BAK1) is required for pattern-triggered
      immunity (PTI) in Arabidopsis thaliana and Nicotiana benthamiana. Tomato (Solanum
      lycopersicum) has three SlSERK members. Two of them exhibit particularly high
      levels of sequence similarity to AtSERK3 and, therefore, were named SlSERK3A and
      SlSERK3B. To characterize a role for SlSERK3A and SlSERK3B in defense, we
      suppressed each gene individually or co-silenced both using virus-induced gene
      silencing (VIGS) in the tomato cv. Moneymaker. Co-silencing SlSERK3A and SlSERK3B
      resulted in spontaneous necrotic lesions and reduced sensitivity to exogenous BR
      treatment. Silencing either SlSERK3A or SlSERK3B resulted in enhanced
      susceptibility to root knot-nematode and to non-pathogenic Pseudomonas syringae
      pv. tomato (Pst) DC3000 hrcC indicating that both SlSERK3s are positive
      regulators of defense. Interestingly, silencing SlSERK3B, but not SlSERK3A,
      resulted in enhanced susceptibility to the pathogenic strain Pst DC3000
      indicating distinct roles for these two SlSERK3 paralogs. SlSERK3A and SlSERK3B
      are active kinases, localized to the plasma membrane, and interact in vivo with
      the Flagellin Sensing 2 receptor in a flg22-dependent manner. Complementation of
      the Atserk3/bak1-4 mutant with either SlSERK3A or SlSERK3B partially rescued the
      mutant phenotype. Thus, SlSERK3A and SlSERK3B are likely to constitute tomato
      orthologs of BAK1. 

PMID- 24675751
TI  - The severity of microvascular dysfunction due to compartment syndrome is
      diminished by the systemic application of CO-releasing molecule-3.
AB  - OBJECTIVES: To examine the protective effects of carbon monoxide (CO), liberated
      from a novel CO-releasing molecule (CORM-3), on the function of compartment
      syndrome (CS)-challenged muscle in a rodent model, thus providing for a potential
      development of a pharmacologic adjunctive treatment for CS. METHODS: Wistar rats
      were randomized into 4 groups: sham (no CS), CS, CS with inactive CORM-3 (iCORM
      3), and CS + CORM-3 (10 mg/kg intraperitoneally). CS was induced by elevation of
      intracompartmental pressure to 30 mm Hg through an infusion of isotonic saline
      into the anterior compartment of the hind limb for 2 hours. Both CORM-3 and iCORM
      3 were injected immediately after fasciotomy. Microvascular perfusion, cellular
      tissue injury, and inflammatory response within the extensor digitorum longus
      muscle were assessed using intravital video microscopy 45 minutes after
      fasciotomy. Systemic levels of tumor necrosis factor alpha (TNF-alpha) were also
      measured. RESULTS: Elevation of intracompartmental pressure resulted in
      significant microvascular perfusion deficits (23% +/- 2% continuously perfused
      capillaries in CS vs. 76% +/- 4% in sham, P < 0.0001; 55% +/- 2% nonperfused
      capillaries in CS vs. 13% +/- 2% in sham, P < 0.0001), significant increase in
      tissue injury (ethidium bromide/bisbenzimide of 0.31 +/- 0.05 in CS vs. 0.05 +/-
      0.03 in sham, P < 0.0001) and adherent leukocytes (13.7 +/- 0.9 in CS vs. 1.8 +/-
      0.5 in sham, P < 0.0001), and a progressive rise in systemic TNF-alpha. CORM-3
      (but not iCORM-3) treatment restored the number of continuously perfused
      capillaries (57% +/- 5%, P < 0.001), diminished tissue injury (ethidium
      bromide/bisbenzimide of 0.07 +/- 0.01, P < 0.001), reversed the CS-associated
      rise in TNF-alpha, and decreased leukocyte adherence (0.6 +/- 0.3, P < 0.001).
      CONCLUSIONS: CORM-3 displays a potent protective/anti-inflammatory action in an
      experimental model of CS, suggesting a potential therapeutic application to
      patients at risk of developing CS.

PMID- 24675752
TI  - Endogenous estrogen exacerbates UV-induced inflammation and photoaging in mice.

PMID- 24675753
TI  - A mutation in TP63 causing a mild ectodermal dysplasia phenotype.

PMID- 24675755
TI  - A comprehensive model of the phototransduction cascade in mouse rod cells.
AB  - Vertebrate visual phototransduction is perhaps the most well-studied G-protein
      signaling pathway. A wealth of available biochemical and electrophysiological
      data has resulted in a rich history of mathematical modeling of the system.
      However, while the most comprehensive models have relied upon amphibian
      biochemical and electrophysiological data, modern research typically employs
      mammalian species, particularly mice, which exhibit significantly faster
      signaling dynamics. In this work, we present an adaptation of a previously
      published, comprehensive model of amphibian phototransduction that can produce
      quantitatively accurate simulations of the murine photoresponse. We demonstrate
      the ability of the model to predict responses to a wide range of stimuli and
      under a variety of mutant conditions. Finally, we employ the model to highlight a
      likely unknown mechanism related to the interaction between rhodopsin and
      rhodopsin kinase. 

PMID- 24675756
TI  - Discovery of a super-strong promoter enables efficient production of heterologous
      proteins in cyanobacteria.
AB  - Cyanobacteria are oxygenic photosynthetic prokaryotes that play important roles
      in the global carbon cycle. Recently, engineered cyanobacteria capable of
      producing various small molecules from CO2 have been developed. However,
      cyanobacteria are seldom considered as factories for producing proteins, mainly
      because of the lack of efficient strong promoters. Here, we report the discovery
      and verification of a super-strong promoter P(cpc560), which contains two
      predicted promoters and 14 predicted transcription factor binding sites (TFBSs).
      Using P(cpc560), functional proteins were produced at a level of up to 15% of
      total soluble protein in the cyanobacterium Synechocystis sp. 6803, a level
      comparable to that produced in Escherichia coli. We demonstrated that the
      presence of multiple TFBSs in P(cpc560) is crucial for its promoter strength.
      Genetically transformable cyanobacteria neither have endotoxins nor form
      inclusion bodies; therefore, P(cpc560) opens the possibility to use cyanobacteria
      as alternative hosts for producing heterogeneous proteins from CO2 and inorganic
      nutrients.

PMID- 24675758
TI  - A fast and accurate sparse continuous signal reconstruction by homotopy DCD with
      non-convex regularization.
AB  - In recent years, various applications regarding sparse continuous signal recovery
      such as source localization, radar imaging, communication channel estimation,
      etc., have been addressed from the perspective of compressive sensing (CS)
      theory. However, there are two major defects that need to be tackled when
      considering any practical utilization. The first issue is off-grid problem caused
      by the basis mismatch between arbitrary located unknowns and the pre-specified
      dictionary, which would make conventional CS reconstruction methods degrade
      considerably. The second important issue is the urgent demand for low-complexity
      algorithms, especially when faced with the requirement of real-time
      implementation. In this paper, to deal with these two problems, we have presented
      three fast and accurate sparse reconstruction algorithms, termed as HR-DCD, Hlog
      DCD and Hlp-DCD, which are based on homotopy, dichotomous coordinate descent
      (DCD) iterations and non-convex regularizations, by combining with the grid
      refinement technique. Experimental results are provided to demonstrate the
      effectiveness of the proposed algorithms and related analysis. 

PMID- 24675759
TI  - Locatable-body temperature monitoring based on semi-active UHF RFID tags.
AB  - This paper presents the use of radio-frequency identification (RFID) technology
      for the real-time remote monitoring of body temperature, while an associated
      program can determine the location of the body carrying the respective sensor.
      The RFID chip's internal integrated temperature sensor is used for both the human
      body temperature detection and as a measurement device, while using radio
      frequency communication to broadcast the temperature information. The adopted
      RFID location technology makes use of reference tags together with a nearest
      neighbor localization algorithm and a multiple-antenna time-division multiplexing
      location system. A graphical user interface (GUI) was developed for collecting
      temperature and location data for the data fusion by using RFID protocols. With a
      puppy as test object, temperature detection and localization experiments were
      carried out. The measured results show that the applied method, when using a
      mercury thermometer for comparison in terms of measuring the temperature of the
      dog, has a good consistency, with an average temperature error of 0.283  degrees
      C. When using the associated program over the area of 12.25 m2, the average
      location error is of 0.461 m, which verifies the feasibility of the sensor
      carrier location by using the proposed program. 

PMID- 24675757
TI  - Hybrid integrated label-free chemical and biological sensors.
AB  - Label-free sensors based on electrical, mechanical and optical transduction
      methods have potential applications in numerous areas of society, ranging from
      healthcare to environmental monitoring. Initial research in the field focused on
      the development and optimization of various sensor platforms fabricated from a
      single material system, such as fiber-based optical sensors and silicon nanowire
      based electrical sensors. However, more recent research efforts have explored
      designing sensors fabricated from multiple materials. For example, synthetic
      materials and/or biomaterials can also be added to the sensor to improve its
      response toward analytes of interest. By leveraging the properties of the
      different material systems, these hybrid sensing devices can have significantly
      improved performance over their single-material counterparts (better sensitivity,
      specificity, signal to noise, and/or detection limits). This review will briefly
      discuss some of the methods for creating these multi-material sensor platforms
      and the advances enabled by this design approach. 

PMID- 24675760
TI  - Language model applications to spelling with Brain-Computer Interfaces.
AB  - Within the Ambient Assisted Living (AAL) community, Brain-Computer Interfaces
      (BCIs) have raised great hopes as they provide alternative communication means
      for persons with disabilities bypassing the need for speech and other motor
      activities. Although significant advancements have been realized in the last
      decade, applications of language models (e.g., word prediction, completion) have
      only recently started to appear in BCI systems. The main goal of this article is
      to review the language model applications that supplement non-invasive BCI-based
      communication systems by discussing their potential and limitations, and to
      discern future trends. First, a brief overview of the most prominent BCI spelling
      systems is given, followed by an in-depth discussion of the language models
      applied to them. These language models are classified according to their
      functionality in the context of BCI-based spelling: the static/dynamic nature of
      the user interface, the use of error correction and predictive spelling, and the
      potential to improve their classification performance by using language models.
      To conclude, the review offers an overview of the advantages and challenges when
      implementing language models in BCI-based communication systems when implemented
      in conjunction with other AAL technologies. 

PMID- 24675761
TI  - Broadly reactive human CD8 T cells that recognize an epitope conserved between
      VZV, HSV and EBV.
AB  - Human herpesviruses are important causes of potentially severe chronic infections
      for which T cells are believed to be necessary for control. In order to examine
      the role of virus-specific CD8 T cells against Varicella Zoster Virus (VZV), we
      generated a comprehensive panel of potential epitopes predicted in silico and
      screened for T cell responses in healthy VZV seropositive donors. We identified a
      dominant HLA-A*0201-restricted epitope in the VZV ribonucleotide reductase
      subunit 2 and used a tetramer to analyze the phenotype and function of epitope
      specific CD8 T cells. Interestingly, CD8 T cells responding to this VZV epitope
      also recognized homologous epitopes, not only in the other alpha-herpesviruses,
      HSV-1 and HSV-2, but also the gamma-herpesvirus, EBV. Responses against these
      epitopes did not depend on previous infection with the originating virus, thus
      indicating the cross-reactive nature of this T cell population. Between
      individuals, the cells demonstrated marked phenotypic heterogeneity. This was
      associated with differences in functional capacity related to increased
      inhibitory receptor expression (including PD-1) along with decreased expression
      of co-stimulatory molecules that potentially reflected their stimulation history.
      Vaccination with the live attenuated Zostavax vaccine did not efficiently
      stimulate a proliferative response in this epitope-specific population. Thus, we
      identified a human CD8 T cell epitope that is conserved in four clinically
      important herpesviruses but that was poorly boosted by the current adult VZV
      vaccine. We discuss the concept of a "pan-herpesvirus" vaccine that this
      discovery raises and the hurdles that may need to be overcome in order to achieve
      this. 

PMID- 24675762
TI  - Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 promotes cell proliferation
      and migration by upregulating DNMT1 via STAT3 activation.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with
      Kaposi's sarcoma (KS), the most common AIDS-related malignancy. KSHV vIL-6
      promotes KS development, but the exact mechanisms remain unclear. Here, we
      reported that KSHV vIL-6 enhanced the expression of DNA methyltransferase 1
      (DNMT1) in endothelial cells,increased the global genomic DNA methylation, and
      promoted cell proliferation and migration. And this effect could be blocked by
      the DNA methyltransferase inhibitor, 5-azadeoxycytidine. We also showed that vIL
      6 induced up-regulation of DNMT1 was dependent on STAT3 activation. Therefore,
      the present study suggests that vIL-6 plays a role in KS tumorigenesis partly by
      activating DNMT1 and inducing aberrant DNA methylation, and it might be a
      potential target for KS therapy. 

PMID- 24675764
TI  - Active matrix metalloprotease-9 is associated with the collagen capsule
      surrounding the Madurella mycetomatis grain in mycetoma.
AB  - Madurella mycetomatis is the main causative organism of eumycetoma, a persistent,
      progressive granulomatous infection. After subcutaneous inoculation M.
      mycetomatis organizes itself in grains inside a granuloma with excessive collagen
      accumulation surrounding it. This could be contributing to treatment failure
      towards currently used antifungal agents. Due to their pivotal role in tissue
      remodelling, matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) or tissue
      inhibitor of metalloproteinases (TIMP) might be involved in this process. Local
      MMP-2 and MMP-9 expression was assessed by immunohistochemistry while absolute
      serum levels of these enzymes were determined in mycetoma patients and healthy
      controls by performing ELISAs. The presence of active MMP was determined by
      gelatin zymography. We found that both MMP-2 and MMP-9 are expressed in the
      mycetoma lesion, but the absolute MMP-2, -9, and TIMP-1 serum levels did not
      significantly differ between patients and controls. However, active MMP-9 was
      found in sera of 36% of M. mycetomatis infected subjects, whereas this active
      form was absent in sera of controls (P<0.0001). MMP-2, MMP-9, and TIMP-1
      polymorphisms in mycetoma patients and healthy controls were determined through
      PCR-RFLP or sequencing. A higher T allele frequency in TIMP-1 (+372) SNP was
      observed in male M. mycetomatis mycetoma patients compared to controls. The
      presence of active MMP-9 in mycetoma patients suggest that MMP-9 is activated or
      synthesized by inflammatory cells upon M. mycetomatis infection. Inhibiting MMP-9
      activity with doxycycline could prevent collagen accumulation in mycetoma, which
      in its turn might make the fungus more accessible to antifungal agents. 

PMID- 24675763
TI  - S-glutathionylation of an auxiliary subunit confers redox sensitivity to Kv4
      channel inactivation.
AB  - Reactive oxygen species (ROS) regulate ion channels, modulate neuronal
      excitability, and contribute to the etiology of neurodegenerative disorders. ROS
      differentially suppress fast "ball-and-chain" N-type inactivation of cloned Kv1
      and Kv3 potassium channels but not of Kv4 channels, likely due to a lack of
      reactive cysteines in Kv4 N-termini. Recently, we discovered that N-type
      inactivation of Kv4 channel complexes can be independently conferred by certain N
      terminal variants of Kv4 auxiliary subunits (DPP6a, DPP10a). Here, we report that
      both DPP6a and DPP10a, like Kv subunits with redox-sensitive N-type inactivation,
      contain a highly conserved cysteine in their N-termini (Cys-13). To test if N
      type inactivation mediated by DPP6a or DPP10a is redox sensitive, Xenopus oocyte
      recordings were performed to examine the effects of two common oxidants, tert
      butyl hydroperoxide (tBHP) and diamide. Both oxidants markedly modulate DPP6a- or
      DPP10a-conferred N-type inactivation of Kv4 channels, slowing the overall
      inactivation and increasing the peak current. These functional effects are fully
      reversed by the reducing agent dithiothreitol (DTT) and appear to be due to a
      selective modulation of the N-type inactivation mediated by these auxiliary
      subunits. Mutation of DPP6a Cys-13 to serine eliminated the tBHP or diamide
      effects, confirming the importance of Cys-13 to the oxidative regulation.
      Biochemical studies designed to elucidate the underlying molecular mechanism show
      no evidence of protein-protein disulfide linkage formation following cysteine
      oxidation. Instead, using a biotinylated glutathione (BioGEE) reagent, we
      discovered that oxidation by tBHP or diamide leads to S-glutathionylation of Cys
      13, suggesting that S-glutathionylation underlies the regulation of fast N-type
      inactivation by redox. In conclusion, our studies suggest that Kv4-based A-type
      current in neurons may show differential redox sensitivity depending on whether
      DPP6a or DPP10a is highly expressed, and that the S-glutathionylation mechanism
      may play a previously unappreciated role in mediating excitability changes and
      neuropathologies associated with ROS. 

PMID- 24675766
TI  - Quantum phase transitions and phase diagram for a one-dimensional p-wave
      superconductor with an incommensurate potential.
AB  - The effect of the incommensurate potential is studied for the one-dimensional p
      wave superconductor. It is determined by analyzing various properties, such as
      the superconducting gap, the long-range order of the correlation function, the
      inverse participation ratio and the Z2 topological invariant, etc. In particular,
      two important aspects of the effect are investigated: (1) as disorder, the
      incommensurate potential destroys the superconductivity and drives the system
      into the Anderson localized phase; (2) as a quasi-periodic potential, the
      incommensurate potential causes band splitting and turns the system with certain
      chemical potential into the band insulator phase. A full phase diagram is also
      presented in the chemical potential-incommensurate potential strength plane. 

PMID- 24675765
TI  - Investigation of inflammation and tissue patterning in the gut using a Spatially
      Explicit General-purpose Model of Enteric Tissue (SEGMEnT).
AB  - The mucosa of the intestinal tract represents a finely tuned system where tissue
      structure strongly influences, and is turn influenced by, its function as both an
      absorptive surface and a defensive barrier. Mucosal architecture and histology
      plays a key role in the diagnosis, characterization and pathophysiology of a host
      of gastrointestinal diseases. Inflammation is a significant factor in the
      pathogenesis in many gastrointestinal diseases, and is perhaps the most
      clinically significant control factor governing the maintenance of the mucosal
      architecture by morphogenic pathways. We propose that appropriate
      characterization of the role of inflammation as a controller of enteric mucosal
      tissue patterning requires understanding the underlying cellular and molecular
      dynamics that determine the epithelial crypt-villus architecture across a range
      of conditions from health to disease. Towards this end we have developed the
      Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT) to
      dynamically represent existing knowledge of the behavior of enteric epithelial
      tissue as influenced by inflammation with the ability to generate a variety of
      pathophysiological processes within a common platform and from a common knowledge
      base. In addition to reproducing healthy ileal mucosal dynamics as well as a
      series of morphogen knock-out/inhibition experiments, SEGMEnT provides insight
      into a range of clinically relevant cellular-molecular mechanisms, such as a
      putative role for Phosphotase and tensin homolog/phosphoinositide 3-kinase
      (PTEN/PI3K) as a key point of crosstalk between inflammation and morphogenesis,
      the protective role of enterocyte sloughing in enteric ischemia-reperfusion and
      chronic low level inflammation as a driver for colonic metaplasia. These results
      suggest that SEGMEnT can serve as an integrating platform for the study of
      inflammation in gastrointestinal disease. 

PMID- 24675769
TI  - Measurement of fetal abdominal and subscapular subcutaneous tissue thickness
      during pregnancy to predict macrosomia: a pilot study.
AB  - This study assessed the growth trends and reference ranges of the ultrasound
      parameters, fetal abdominal subcutaneous tissue thickness (ASTT) and subscapular
      subcutaneous tissue thickness (SSTT), in the last two trimesters of normal
      pregnancy in a Chinese population. We recruited 744 healthy women with singleton
      pregnancies. The ASTT and SSTT were evaluated at different times between 21 and
      36 weeks of gestation. The correlations between these parameters and fetal
      gestational weeks were assessed using linear regression analysis. Both ASTT and
      SSTT increased with gestation, and both parameters showed a strong correlation
      with gestation (ASTT vs. GA, R(2) = 0.792; P<0.0001; SSTT vs. GA, R(2) = 0.302;
      P<0.0001). Time-specific reference ranges, including 5th, 50th and 95th
      percentiles and means +/- SD, were constructed for ASTT and SSTT. These results
      provide a preliminary reference range to evaluate whether fetal development and
      maternal metabolic health is normal or not in a Chinese population.

PMID- 24675768
TI  - A novel curcumin analog (H-4073) enhances the therapeutic efficacy of cisplatin
      treatment in head and neck cancer.
AB  - Chemotherapy constitutes the standard modality of treatment for localized head
      and neck squamous cell carcinomas (HNSCC). However, many patients fail to respond
      and relapse after this treatments due to the acquisition of chemo-resistance.
      Therefore, there is an urgent need to develop novel drugs that could reverse the
      resistant phenotype. Curcumin, the constituent of the spice turmeric has been
      shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties
      in several tumor types. However, use of curcumin has been limited due to its poor
      bio-absorption. Recently, a novel class of curcumin analogs, based on
      diarylidenylpiperidones (DAP), has been developed by incorporating a piperidone
      link to the beta-diketone structure and fluoro substitutions on the phenyl
      groups. In this study, we evaluated the effectiveness of H-4073, a
      parafluorinated variant of DAP, using both in vitro and in vivo head and neck
      cancer models. Our results demonstrate that H-4073 is a potent anti-tumor agent
      and it significantly inhibited cell proliferation in all the HNSCC cell lines
      tested in a dose-dependent manner. In addition, pretreatment of cisplatin
      resistant HNSCC cell lines with H-4073 significantly reversed the chemo
      resistance as observed by cell viability assay (MTT), apoptosis assay (Annexin V
      binding) and cleaved caspase-3 (Western blot). H-4073 mediated its anti-tumor
      effects by inhibiting JAK/STAT3, FAK, Akt and VEGF signaling pathways that play
      important roles in cell proliferation, migration, survival and angiogenesis. In
      the SCID mouse xenograft model, H-4073 significantly enhanced the anti-tumor and
      anti-angiogenesis effects of cisplatin, with no added systemic toxicity.
      Interestingly, H-4073 inhibited tumor angiogenesis by blocking VEGF production by
      tumor cells as well as directly inhibiting endothelial cell function. Taken
      together, our results suggest that H-4073 is a potent anti-tumor agent and it can
      be used to overcome chemotherapy resistance in HNSCC. 

PMID- 24675770
TI  - Stream macroinvertebrate response models for bioassessment metrics: addressing
      the issue of spatial scale.
AB  - We developed independent predictive disturbance models for a full regional data
      set and four individual ecoregions (Full Region vs. Individual Ecoregion models)
      to evaluate effects of spatial scale on the assessment of human landscape
      modification, on predicted response of stream biota, and the effect of other
      possible confounding factors, such as watershed size and elevation, on model
      performance. We selected macroinvertebrate sampling sites for model development
      (n = 591) and validation (n = 467) that met strict screening criteria from four
      proximal ecoregions in the northeastern U.S.: North Central Appalachians, Ridge
      and Valley, Northeastern Highlands, and Northern Piedmont. Models were developed
      using boosted regression tree (BRT) techniques for four macroinvertebrate
      metrics; results were compared among ecoregions and metrics. Comparing within a
      region but across the four macroinvertebrate metrics, the average richness of
      tolerant taxa (RichTOL) had the highest R(2) for BRT models. Across the four
      metrics, final BRT models had between four and seven explanatory variables and
      always included a variable related to urbanization (e.g., population density,
      percent urban, or percent manmade channels), and either a measure of hydrologic
      runoff (e.g., minimum April, average December, or maximum monthly runoff) and(or)
      a natural landscape factor (e.g., riparian slope, precipitation, and elevation),
      or a measure of riparian disturbance. Contrary to our expectations, Full Region
      models explained nearly as much variance in the macroinvertebrate data as
      Individual Ecoregion models, and taking into account watershed size or elevation
      did not appear to improve model performance. As a result, it may be advantageous
      for bioassessment programs to develop large regional models as a preliminary
      assessment of overall disturbance conditions as long as the range in natural
      landscape variability is not excessive.

PMID- 24675767
TI  - An insulin-to-insulin regulatory network orchestrates phenotypic specificity in
      development and physiology.
AB  - Insulin-like peptides (ILPs) play highly conserved roles in development and
      physiology. Most animal genomes encode multiple ILPs. Here we identify mechanisms
      for how the forty Caenorhabditis elegans ILPs coordinate diverse processes,
      including development, reproduction, longevity and several specific stress
      responses. Our systematic studies identify an ILP-based combinatorial code for
      these phenotypes characterized by substantial functional specificity and
      diversity rather than global redundancy. Notably, we show that ILPs regulate each
      other transcriptionally, uncovering an ILP-to-ILP regulatory network that
      underlies the combinatorial phenotypic coding by the ILP family. Extensive
      analyses of genetic interactions among ILPs reveal how their signals are
      integrated. A combined analysis of these functional and regulatory ILP
      interactions identifies local genetic circuits that act in parallel and interact
      by crosstalk, feedback and compensation. This organization provides emergent
      mechanisms for phenotypic specificity and graded regulation for the combinatorial
      phenotypic coding we observe. Our findings also provide insights into how large
      hormonal networks regulate diverse traits. 

PMID- 24675772
TI  - Plasma biochemical and PCV ranges for healthy, wild, immature hawksbill
      (Eretmochelys imbricata) sea turtles.
AB  - In recent years, the use of blood chemistry as a diagnostic tool for sea turtles
      has been demonstrated, but much of its effectiveness relies on reference
      intervals. The first comprehensive blood chemistry values for healthy wild
      hawksbill (Eretmochelys imbricata) sea turtles are presented. Nineteen blood
      chemistry analytes and packed cell volume were analysed for 40 clinically healthy
      juvenile hawksbill sea turtles captured from a rocky reef habitat in northern
      Australia. We used four statistical approaches to calculate reference intervals
      and to investigate their use with non-normal distributions and small sample
      sizes, and to compare upper and lower limits between methods. Eleven analytes
      were correlated with curved carapace length indicating that body size should be
      considered when designing future studies and interpreting analyte values.

PMID- 24675771
TI  - Mitochondrial dysfunction in Gulf War illness revealed by 31Phosphorus Magnetic
      Resonance Spectroscopy: a case-control study.
AB  - BACKGROUND: Approximately 1/3 of 1990-1 Gulf War veterans developed chronic
      multisymptom health problems. Implicated exposures bear mechanisms that adversely
      affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and
      muscle are aerobically demanding); with protean additional domains affected,
      compatible with mitochondrial impairment. Recent evidence supports treatments
      targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms.
      However, no evidence has directly documented mitochondrial or bioenergetic
      impairment in Gulf War illness. OBJECTIVE: We sought to objectively assess for
      mitochondrial dysfunction, examining post-exercise phosphocreatine-recovery time
      constant (PCr-R) using (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P
      MRS), in Gulf War veterans with Gulf War illness compared to matched healthy
      controls. PCr-R has been described as a "robust and practical" index of
      mitochondrial status. DESIGN AND PARTICIPANTS: Case-control study from 2012-2013.
      Fourteen community-dwelling Gulf War veterans and matched controls from the San
      Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness,
      and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and
      ethnicity. OUTCOME MEASURE: Calf muscle phosphocreatine was evaluated by (31)P
      MRS at rest, through 5 minutes of foot pedal depression exercise, and in
      recovery, to assess PCr-R. Paired t-tests compared cases to matched controls.
      RESULTS: PCr-R was significantly prolonged in Gulf War illness cases vs their
      matched controls: control values, mean +/- SD, 29.0 +/- 8.7 seconds; case values
      46.1 +/- 18.0 seconds; difference 17.1 +/- 14.9 seconds; p = 0.023. PCr-R was
      longer for cases relative to their matched controls for all but one pair;
      moreover while values clustered under 31 seconds for all but one control, they
      exceeded 35 seconds (with a spread up to 70 seconds) for all but one case.
      DISCUSSION: These data provide the first direct evidence supporting mitochondrial
      dysfunction in Gulf War illness. Findings merit replication in a larger study
      and/or corroboration with additional mitochondrial assessment tools.

PMID- 24675773
TI  - Impact of water-soaking on the nutrient composition of UK hays.

PMID- 24675774
TI  - Probing secondary interactions in biomolecular recognition by dynamic
      combinatorial chemistry.
AB  - Artificial multivalent recognition systems offer promising perspectives for
      developing synthetic compounds capable of interacting effectively and selectively
      with biomolecules in aqueous medium. The identification of multi-point binding
      ligands requires screening of a large number of complex structures, with
      different spacers, different ligands, and varying valency. This represents a
      challenge for rational design approaches. On the other hand, the use of dynamic
      covalent chemistry enables a target-driven one-pot screening approach for probing
      secondary interactions, thereby facilitating the identification of multivalent
      recognition systems that optimally combine multiple fragments. Herein we review
      the recent developments in the implementation of dynamic combinatorial chemistry
      for probing secondary interactions and thereby identify multi-point binding
      ligands of biomolecules. 

PMID- 24675775
TI  - The effect of modified eggs and an egg-yolk based beverage on serum lutein and
      zeaxanthin concentrations and macular pigment optical density: results from a
      randomized trial.
AB  - Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the
      progression of age-related macular degeneration. The aim of this study was to
      investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched
      egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations
      and macular pigment levels. Naturally enriched eggs were made by increasing the
      levels of the xanthophylls lutein and zeaxanthin in the feed given to laying
      hens. One hundred healthy volunteers were recruited and randomized into 5 groups
      for 90 days. Group one added one normal egg to their daily diet and group two
      received a lutein enriched egg-yolk based beverage. Group three added one lutein
      enriched egg and group four one zeaxanthin enriched egg to their diet. Group five
      was the control group and individuals in this group did not modify their daily
      diet. Serum lutein and zeaxanthin concentrations and macular pigment densities
      were obtained at baseline, day 45 and day 90. Macular pigment density was
      measured by heterochromatic flicker photometry. Serum lutein concentration in the
      lutein enriched egg and egg yolk-based beverage groups increased significantly
      (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration
      was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%).
      No changes were observed in macular pigment density in the various groups tested.
      The results indicate that daily consumption of lutein or zeaxanthin enriched egg
      yolks as well as an egg yolk-based beverage show increases in serum lutein and
      zeaxanthin levels that are comparable with a daily use of 5 mg supplements. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00527553.

PMID- 24675776
TI  - Crk adaptors negatively regulate actin polymerization in pedestals formed by
      enteropathogenic Escherichia coli (EPEC) by binding to Tir effector.
AB  - Infections by enteropathogenic Escherichia coli (EPEC) cause diarrhea linked to
      high infant mortality in developing countries. EPEC adheres to epithelial cells
      and induces the formation of actin pedestals. Actin polymerization is driven
      fundamentally through signaling mediated by Tir bacterial effector protein, which
      inserts in the plasma membrane of the infected cell. Tir binds Nck adaptor
      proteins, which in turn recruit and activate N-WASP, a ubiquitous member of the
      Wiskott-Aldrich syndrome family of proteins. N-WASP activates the Arp2/3 complex
      to promote actin polymerization. Other proteins aside from components of the Tir
      Nck-N-WASP pathway are recruited to the pedestals but their functions are
      unknown. Here we investigate the function of two alternatively spliced isoforms
      of Crk adaptors (CrkI/II) and the paralog protein CrkL during pedestal formation
      by EPEC. We found that the Crk isoforms act as redundant inhibitors of pedestal
      formation. The SH2 domain of CrkII and CrkL binds to phosphorylated tyrosine 474
      of Tir and competes with Nck to bind Tir, preventing its recruitment to pedestals
      and thereby inhibiting actin polymerization. EPEC infection induces
      phosphorylation of the major regulatory tyrosine in CrkII and CrkL, possibly
      preventing the SH2 domain of these proteins from interacting with Tir.
      Phosphorylated CrkII and CrkL proteins localize specifically to the plasma
      membrane in contact with EPEC. Our study uncovers a novel role for Crk adaptors
      at pedestals, opening a new perspective in how these oncoproteins regulate actin
      polymerization. 

PMID- 24675778
TI  - Mitochondrial proteomics investigation of a cellular model of impaired dopamine
      homeostasis, an early step in Parkinson's disease pathogenesis.
AB  - Impaired dopamine homeostasis is an early event in the pathogenesis of
      Parkinson's disease. Generation of intracellular reactive oxygen species
      consequent to dopamine oxidation leads to mitochondrial dysfunction and
      eventually cell death. Alterations in the mitochondrial proteome due to dopamine
      exposure were investigated in the SH-SY5Y human neuroblastoma cell line. The
      combination of two orthogonal proteomic approaches, two-dimensional
      electrophoresis and shotgun proteomics (proteomeXchange dataset PXD000838), was
      used to highlight the specific pathways perturbed by the increase of
      intracellular dopamine, in comparison with those perturbed by a specific
      mitochondrial toxin (4-methylphenylpyridinium, MPP(+)), a neurotoxin causing
      Parkinsonism-like symptoms in animal models. Proteins altered by MPP(+) did not
      completely overlap with those affected by dopamine treatment. In particular, the
      MPP(+) target complex I component NADH dehydrogenase [ubiquinone] iron-sulfur
      protein 3 was not affected by dopamine together with 26 other proteins. The
      comparison of proteomics approaches highlighted the fragmentation of some
      mitochondrial proteins, suggesting an alteration of the mitochondrial protease
      activity. Pathway and disease association analysis of the proteins affected by
      dopamine revealed the overrepresentation of the Parkinson's disease and the
      parkin-ubiquitin proteasomal system pathways and of gene ontologies associated
      with generation of precursor metabolites and energy, response to topologically
      incorrect proteins and programmed cell death. These alterations may be globally
      interpreted in part as the result of a direct effect of dopamine on mitochondria
      (e.g. alteration of the mitochondrial protease activity) and in part as the
      effect on mitochondria of a general activation of cellular processes (e.g.
      regulation of programmed cell death). 

PMID- 24675777
TI  - Fusion FISH imaging: single-molecule detection of gene fusion transcripts in
      situ.
AB  - Double-stranded DNA breaks occur on a regular basis in the human genome as a
      consequence of genotoxic stress and errors during replication. Usually these
      breaks are rapidly and faithfully repaired, but occasionally different
      chromosomes, or different regions of the same chromosome, are fused to each
      other. Some of these aberrant chromosomal translocations yield functional
      recombinant genes, which have been implicated as the cause of a number of
      lymphomas, leukemias, sarcomas, and solid tumors. Reliable methods are needed for
      the in situ detection of the transcripts encoded by these recombinant genes. We
      have developed just such a method, utilizing single-molecule fluorescence in situ
      hybridization (sm-FISH), in which approximately 50 short fluorescent probes bind
      to adjacent sites on the same mRNA molecule, rendering each target mRNA molecule
      visible as a diffraction-limited spot in a fluorescence microscope. Utilizing
      this method, gene fusion transcripts are detected with two differently colored
      probe sets, each specific for one of the two recombinant segments of a target
      mRNA; enabling the fusion transcripts to be seen in the microscope as distinct
      spots that fluoresce in both colors. We demonstrate this method by detecting the
      BCR-ABL fusion transcripts that occur in chronic myeloid leukemia cells, and by
      detecting the EWSR1-FLI1 fusion transcripts that occur in Ewing's sarcoma cells.
      This technology should pave the way for accurate in situ typing of many cancers
      that are associated with, or caused by, fusion transcripts. 

PMID- 24675779
TI  - One-pot synthesis of graphene-supported monodisperse Pd nanoparticles as catalyst
      for formic acid electro-oxidation.
AB  - To synthesize monodisperse palladium nanoparticles dispersed on reduced graphene
      oxide (RGO) sheets, we have developed an easy and scalable solvothermal reduction
      method from an organic solution system. The RGO-supported palladium nanoparticles
      with a diameter of 3.8 nm are synthesized in N-methyl-2-pyrrolidone (NMP) and in
      the presence of oleylamine and trioctylphosphine, which facilitates simultaneous
      reduction of graphene oxide and formation of Pd nanocrystals. So-produced Pd/RGO
      was tested for potential use as electrocatalyst for the electro-oxidation of
      formic acid. Pd/RGO catalyzes formic acid oxidation very well compared to
      Pd/Vulcan XC-72 catalyst. This synthesis method is a new way to prepare excellent
      electrocatalysts, which is of great significance in energy-related catalysis.

PMID- 24675780
TI  - Core-shell potassium niobate nanowires for enhanced nonlinear optical effects.
AB  - We demonstrate the synthesis as well as the optical characterization of core
      shell nanowires. The wires consist of a potassium niobate (KNbO3) core and a gold
      shell. The nonlinear optical properties of the core are combined with the
      plasmonic resonance of the shell and offer an enhanced optical signal in the near
      infrared spectral range. We compare two different functionalization schemes of
      the core material prior to the shell growth process: silanization and
      polyelectrolyte. We show that the latter leads to a smoother and complete core
      shell nanostructure and an easier-to-use synthesis process. A Mie-theory based
      theoretical approach is presented to model the enhanced second-harmonic generated
      (SHG) signal of the core-shell wires, illustrating the influence of the
      fabrication-induced varying geometrical factors of wire radius and shell
      thickness. A spectroscopic measurement on a core-shell nanowire shows a strong
      localized surface plasmon resonance close to 900 nm, which matches with the SHG
      resonance obtained from nonlinear optical experiments with the same nanowire.
      According to the simulation, this corresponds to a wire radius of 35 nm and a
      shell thickness of 7.5 nm. By comparing SHG signals measured from an uncoated
      nanowire and the coated one, we obtain a 250 times enhancement factor. This is
      less than the calculated enhancement, which considers a cylindrical nanowire with
      a perfectly smooth shell. Thus, we explain this discrepancy mainly with the
      roughness of the synthesized gold shell. 

PMID- 24675781
TI  - Learning and memory: Out of body, out of mind.

PMID- 24675782
TI  - Neurodegeneration: Ageing neurons need REST.

PMID- 24675783
TI  - Inherent and transferable stabilization energies of carbon- and heteroatom
      centred radicals on the same relative scale and their applications.
AB  - Accurate G3(MP2)-RAD calculations are used to predict 264 R-H, R-CH3, R-Cl and R
      R bond dissociation energies for a wide-ranging test set of carbon and non-carbon
      centred R radicals. The data are used to calculate a set of inherent and
      transferrable radical stabilization energies, denoted RSEEt, which ranks the
      inherent stability of the 66 radicals studied on the same relative scale,
      irrespective of the nature of the radical centre. The Pauling electronegativity
      parameter for each radical is also calculated from the same data, along with the
      radical's inherent bonding ability D[R-R]calc. This latter quantity is defined as
      the R-R bond dissociation energy expected in the absence of direct steric or
      resonance interactions that are present in R-R but absent in R-CH3 and R-Cl. We
      show that the differences between D[R-R] and D[R-R]calc are typically very small
      except when R is sterically bulky, or there is a chain of (hyper)conjugation
      across the R-R bond. In such cases the difference between D[R-R] and D[R-R]calc
      provides a convenient means of quantifying the stabilization or destabilization
      of R-R due to these interactions. The predictability of the scheme is
      demonstrated by using these radical stabilities to calculate R-R' bond
      dissociation energies for 234 combinations of the 66 radicals studied, chosen to
      exclude steric or resonance interactions in the R-R' bond. The predicted bond
      energies lie within an average of 1.6 kcal mol(-1) from directly measured or
      calculated literature values. 

PMID- 24675784
TI  - A stable Janus bis(maloNHC) and its zwitterionic coinage metal complexes.
AB  - The first stable dianionic Janus-type bis(maloNHC) was isolated and
      characterized. Details on the chemistry of this biscarbene with respect to its
      ability to support catalytically relevant metal complexes are provided. The
      molecular structures of two dinuclear gold and silver complexes were determined
      by X-ray crystallography. 

PMID- 24675785
TI  - Differential responses of emergent intertidal coral reef fauna to a large-scale
      El-Nino southern oscillation event: sponge and coral resilience.
AB  - There is a paucity of information on the impacts of the 1997-8 El Nino event and
      subsequent climatic episodes on emergent intertidal coral reef assemblages. Given
      the environmental variability intertidal reefs experience, such reefs may
      potentially be more resilient to climatic events and provide important insights
      into the adaptation of reef fauna to future ocean warming. Here we report the
      results of a 17-year (1995-2011) biodiversity survey of four emergent coral reef
      ecosystems in Bahia, Brazil, to assess the impact of a major El Nino event on the
      reef fauna, and determine any subsequent recovery. The densities of two species
      of coral, Favia gravida and Siderastrea stellata, did not vary significantly
      across the survey period, indicating a high degree of tolerance to the El Nino
      associated stress. However, there were marked decreases in the diversity of other
      taxa. Molluscs, bryozoans and ascidians suffered severe declines in diversity and
      abundance and had not recovered to pre-El Nino levels by the end of the study.
      Echinoderms were reduced to a single species in 1999, Echinometra lucunter,
      although diversity levels had recovered by 2002. Sponge assemblages were not
      impacted by the 1997-8 event and their densities had increased by the study end.
      Multivariate analysis indicated that a stable invertebrate community had re
      established on the reefs after the El Nino event, but it has a different overall
      composition to the pre-El Nino community. It is unclear if community recovery
      will continue given more time, but our study highlights that any increase in the
      frequency of large-scale climatic events to more than one a decade is likely to
      result in a persistent lower-diversity state. Our results also suggest some coral
      and sponge species are particularly resilient to the El Nino-associated stress
      and therefore represent suitable models to investigate temperature adaptation in
      reef organisms. 

PMID- 24675786
TI  - Drosophila pheromone-sensing neurons expressing the ppk25 ion channel subunit
      stimulate male courtship and female receptivity.
AB  - As in many species, gustatory pheromones regulate the mating behavior of
      Drosophila. Recently, several ppk genes, encoding ion channel subunits of the
      DEG/ENaC family, have been implicated in this process, leading to the
      identification of gustatory neurons that detect specific pheromones. In a subset
      of taste hairs on the legs of Drosophila, there are two ppk23-expressing,
      pheromone-sensing neurons with complementary response profiles; one neuron
      detects female pheromones that stimulate male courtship, the other detects male
      pheromones that inhibit male-male courtship. In contrast to ppk23, ppk25, is only
      expressed in a single gustatory neuron per taste hair, and males with impaired
      ppk25 function court females at reduced rates but do not display abnormal
      courtship of other males. These findings raised the possibility that ppk25
      expression defines a subset of pheromone-sensing neurons. Here we show that ppk25
      is expressed and functions in neurons that detect female-specific pheromones and
      mediates their stimulatory effect on male courtship. Furthermore, the role of
      ppk25 and ppk25-expressing neurons is not restricted to responses to female
      specific pheromones. ppk25 is also required in the same subset of neurons for
      stimulation of male courtship by young males, males of the Tai2 strain, and by
      synthetic 7-pentacosene (7-P), a hydrocarbon normally found at low levels in both
      males and females. Finally, we unexpectedly find that, in females, ppk25 and
      ppk25-expressing cells regulate receptivity to mating. In the absence of the
      third antennal segment, which has both olfactory and auditory functions,
      mutations in ppk25 or silencing of ppk25-expressing neurons block female
      receptivity to males. Together these results indicate that ppk25 identifies a
      functionally specialized subset of pheromone-sensing neurons. While ppk25 neurons
      are required for the responses to multiple pheromones, in both males and females
      these neurons are specifically involved in stimulating courtship and mating. 

PMID- 24675787
TI  - STDP installs in Winner-Take-All circuits an online approximation to hidden
      Markov model learning.
AB  - In order to cross a street without being run over, we need to be able to extract
      very fast hidden causes of dynamically changing multi-modal sensory stimuli, and
      to predict their future evolution. We show here that a generic cortical
      microcircuit motif, pyramidal cells with lateral excitation and inhibition,
      provides the basis for this difficult but all-important information processing
      capability. This capability emerges in the presence of noise automatically
      through effects of STDP on connections between pyramidal cells in Winner-Take-All
      circuits with lateral excitation. In fact, one can show that these motifs endow
      cortical microcircuits with functional properties of a hidden Markov model, a
      generic model for solving such tasks through probabilistic inference. Whereas in
      engineering applications this model is adapted to specific tasks through offline
      learning, we show here that a major portion of the functionality of hidden Markov
      models arises already from online applications of STDP, without any supervision
      or rewards. We demonstrate the emergent computing capabilities of the model
      through several computer simulations. The full power of hidden Markov model
      learning can be attained through reward-gated STDP. This is due to the fact that
      these mechanisms enable a rejection sampling approximation to theoretically
      optimal learning. We investigate the possible performance gain that can be
      achieved with this more accurate learning method for an artificial grammar task. 

PMID- 24675788
TI  - Identification of internal reference genes for gene expression normalization
      between the two sexes in dioecious white Campion.
AB  - Quantitative real time (qRT)-PCR is a precise and efficient method for studying
      gene expression changes between two states of interest, and is frequently used
      for validating interesting gene expression patterns in candidate genes initially
      identified in genome-wide expression analyses, such as RNA-seq experiments. For
      an adequate normalisation of qRT-PCR data, it is essential to have reference
      genes available whose expression intensities are constant among the different
      states of interest. In this study we present and validate a catalogue of
      traditional and newly identified reference genes that were selected from RNA-seq
      data from multiple individuals from the dioecious plant Silene latifolia with the
      aim of studying gene expression differences between the two sexes in both
      reproductive and vegetative tissues. The catalogue contains more than 15
      reference genes with both stable expression intensities and a range of expression
      intensities in flower buds and leaf tissues. These reference genes were used to
      normalize expression differences between reproductive and vegetative tissues in
      eight candidate genes with sex-biased expression. Our results suggest a trend
      towards a reduced sex-bias in sex-linked gene expression in vegetative tissues.
      In this study, we report on the systematic identification and validation of
      internal reference genes for adequate normalization of qRT-PCR-based analyses of
      gene expression differences between the two sexes in S. latifolia. We also show
      how RNA-seq data can be used efficiently to identify suitable reference genes in
      a wide diversity of species. 

PMID- 24675790
TI  - Malignant Otitis Externa: Evolving Pathogens and Implications for Diagnosis and
      Treatment.
AB  - OBJECTIVE: Malignant otitis externa (MOE) is an invasive infection of the
      temporal bone that is classically caused by Pseudomonas aeruginosa. Increasingly,
      however, nonpseudomonal cases are being reported. The goal of this study was to
      evaluate and compare the clinical presentation and outcomes of cases of MOE
      caused by Pseudomonas versus non-Pseudomonas organisms. STUDY DESIGN:
      Retrospective case series with chart review. SETTING: Tertiary care institution.
      SUBJECTS AND METHODS: Adult patients with diagnoses of MOE between 1995 and 2012
      were identified. Charts were reviewed for history, clinical presentation,
      laboratory data, treatment, and outcomes. RESULTS: Twenty patients diagnosed with
      and treated for MOE at the University of Pittsburgh Medical Center between 1995
      and 2012 were identified. Nine patients (45%) had cultures that grew P
      aeruginosa. Three patients (15%) had cultures that grew methicillin-resistant
      Staphylococcus aureus (MRSA). Signs and symptoms at presentation were similar
      across groups. However, all of the patients with Pseudomonas had diabetes,
      compared with 33% of MRSA-infected patients (P = .046) and 55% of all non
      Pseudomonas-infected patients (P = .04). Patients infected with MRSA were treated
      for an average total of 4.7 more weeks of antibiotic therapy than Pseudomonas
      infected patients (P = .10). Overall, patients with non-Pseudomonas infections
      were treated for a total of 2.4 more weeks than Pseudomonas-infected patients (P
      = .25). CONCLUSIONS: A high index of suspicion for nonpseudomonal organisms
      should be maintained in patients with signs and symptoms of MOE, especially in
      those without diabetes. MRSA is an increasingly implicated organism in MOE.

PMID- 24675789
TI  - Injury in Minipig Parotid Glands following Fractionated Exposure to 30 Gy of
      Ionizing Radiation.
AB  - OBJECTIVE: To explore the effects of 30 Gy of (60)Co gamma-rays on apoptosis and
      reactive oxygen species (ROS) levels in minipig parotid cells as a possible
      mechanism for radiation-induced parotid injury. STUDY DESIGN: Experimental study.
      SETTING: Department of Radiotherapy, First Affiliated Hospital, Guangxi Medical
      University, Nanning, China. SUBJECTS AND METHODS: Forty male minipigs were
      divided into control and irradiated groups. Terminal deoxynucleotidyl transferase
      deoxyuridine triphosphate nick-end labeling was used for detecting apoptosis in
      the parotid cells, immunohistochemistry, and western blots were used to test
      expression of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins,
      and reverse transcription polymerase chain reaction was used to analyze the
      expression of Bcl-2, Bax, p53, and caspase-3 messenger ribonucleic acid. An
      enzyme-linked immunosorbent assay was used to detect ROS levels in the parotid
      tissue. RESULTS: At each time point, the apoptotic rates in the irradiated group
      were higher than those in the control group. Furthermore, the ROS and expression
      levels of Bax, p53, and caspase-3 messenger ribonucleic acid and proteins
      gradually increased and were higher than those in the control group. Conversely,
      the expression of Bcl-2 was decreased in the irradiated group (P < .05).
      CONCLUSIONS: Ionizing radiation induces the production of ROS and promotes
      changes in the expression of several apoptotic proteins, which increases
      apoptosis and likely contributes to the mechanism of radiation-induced parotid
      injury.

PMID- 24675791
TI  - Hole doping by pressure on the 1111 pnictides CaFeAsF and SrFeAsF.
AB  - We determine the pressure phase diagram of the 1111 compounds CaFeAsF and
      SrFeAsF, up to 20 GPa and down to 4 K by electrical resistivity measurements and
      the change of structure up to 40 GPa at room temperature. The antiferromagnetic
      transition temperature, as determined by the derivative peak, shows a minimum at
      ~5 GPa (10 GPa) for the Ca (Sr) compound. For CaFeAsF, superconductivity appears
      at this minimum, coincident with the development of a previously reported
      monoclinic phase. For SrFeAsF, where the orthorhombic and the monoclinic phase
      were reported to coexist, superconductivity exists above P>=1 GPa. Both phase
      diagrams can be scaled by a shift of ~10 GPa pressure at which the volume of
      SrFeAsF and that of CaFeAsF at ambient pressure coincide. The difference of our
      phase diagram with that of electron-doped 1111 samples is accounted for by hole
      doping under pressure, which we verified through electron band structure
      calculations. 

PMID- 24675792
TI  - Metabolic changes in Avena sativa crowns recovering from freezing.
AB  - Extensive research has been conducted on cold acclimation and freezing tolerance
      of fall-sown cereal plants due to their economic importance; however, little has
      been reported on the biochemical changes occurring over time after the freezing
      conditions are replaced by conditions favorable for recovery and growth such as
      would occur during spring. In this study, GC-MS was used to detect metabolic
      changes in the overwintering crown tissue of oat (Avena sativa L.) during a
      fourteen day time-course after freezing. Metabolomic analysis revealed increases
      in most amino acids, particularly proline, 5-oxoproline and arginine, which
      increased greatly in crowns that were frozen compared to controls and correlated
      very significantly with days after freezing. In contrast, sugar and sugar related
      metabolites were little changed by freezing, except sucrose and fructose which
      decreased dramatically. In frozen tissue all TCA cycle metabolites, especially
      citrate and malate, decreased in relation to unfrozen tissue. Alterations in some
      amino acid pools after freezing were similar to those observed in cold
      acclimation whereas most changes in sugar pools after freezing were not. These
      similarities and differences suggest that there are common as well as unique
      genetic mechanisms between these two environmental conditions that are crucial to
      the winter survival of plants. 

PMID- 24675793
TI  - ATR suppresses endogenous DNA damage and allows completion of homologous
      recombination repair.
AB  - DNA replication fork stalling or collapse that arises from endogenous damage
      poses a serious threat to genome stability, but cells invoke an intricate
      signaling cascade referred to as the DNA damage response (DDR) to prevent such
      damage. The gene product ataxia telangiectasia and Rad3-related (ATR) responds
      primarily to replication stress by regulating cell cycle checkpoint control, yet
      it's role in DNA repair, particularly homologous recombination (HR), remains
      unclear. This is of particular interest since HR is one way in which replication
      restart can occur in the presence of a stalled or collapsed fork. Hypomorphic
      mutations in human ATR cause the rare autosomal-recessive disease Seckel
      syndrome, and complete loss of Atr in mice leads to embryonic lethality. We
      recently adapted the in vivo murine pink-eyed unstable (pun) assay for measuring
      HR frequency to be able to investigate the role of essential genes on HR using a
      conditional Cre/loxP system. Our system allows for the unique opportunity to test
      the effect of ATR loss on HR in somatic cells under physiological conditions.
      Using this system, we provide evidence that retinal pigment epithelium (RPE)
      cells lacking ATR have decreased density with abnormal morphology, a decreased
      frequency of HR and an increased level of chromosomal damage. 

PMID- 24675795
TI  - Most associations between transcript features and gene expression are monotonic.
AB  - Dozens of previous studies in the field have dealt with the relations between
      transcript features and their expression. Indeed, understanding the way gene
      expression is encoded in transcripts should not only contribute to disciplines,
      such as functional genomics and molecular evolution, but also to biotechnology
      and human health. Previous studies in the field mainly aimed at predicting
      protein levels of genes based on their transcript features. Most of the models
      employed in this context assume that the effect of each transcript feature on
      gene expression is monotonic. In the current study we aim to understand, for the
      first time, if indeed the relations between transcript features (i.e., the UTRs
      and ORF) and measurements related to the different stages of gene expression is
      monotonic. To this end, we analyze 5432 transcript features and perform gene
      expression measurements (mRNA levels, ribosomal densities, protein levels, etc.)
      of 4367 S. cerevisiae genes. We use the Maximal Information Coefficient (MIC) in
      order to identify potential relations that are not necessarily linear or
      monotonic. Our analyses demonstrate that the relation between most transcript
      features and the examined gene expression measurements is monotonic (only up to 1
      5% of the variables, with significance levels of 0.001, are non-monotonic); in
      addition, in the cases of deviation from monotonicity the relation/deviation is
      very weak. These results should help in guiding the development of computational
      gene expression modeling and engineering, and improve the understanding of this
      process. Furthermore, the relatively simple relations between a transcript's
      nucleotide composition and its expression should contribute towards better
      understanding of transcript evolution at the molecular level. 

PMID- 24675794
TI  - Evaluation of nanolipoprotein particles (NLPs) as an in vivo delivery platform.
AB  - Nanoparticles hold great promise for the delivery of therapeutics, yet
      limitations remain with regards to the use of these nanosystems for efficient
      long-lasting targeted delivery of therapeutics, including imparting functionality
      to the platform, in vivo stability, drug entrapment efficiency and toxicity. To
      begin to address these limitations, we evaluated the functionality, stability,
      cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of
      nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high
      density lipoproteins (HDLs). We found that a wide range of molecules could be
      reliably conjugated to the NLP, including proteins, single-stranded DNA, and
      small molecules. The NLP was also found to be relatively stable in complex
      biological fluids and displayed no cytotoxicity in vitro at doses as high as 320
      ug/ml. In addition, we observed that in vivo administration of the NLP daily for
      14 consecutive days did not induce significant weight loss or result in lesions
      on excised organs. Furthermore, the NLPs did not display overt immunogenicity
      with respect to antibody generation. Finally, the biodistribution of the NLP in
      vivo was found to be highly dependent on the route of administration, where
      intranasal administration resulted in prolonged retention in the lung tissue.
      Although only a select number of NLP compositions were evaluated, the findings of
      this study suggest that the NLP platform holds promise for use as both a targeted
      and non-targeted in vivo delivery vehicle for a range of therapeutics. 

PMID- 24675796
TI  - Nitrogen and water availability to tomato plants triggers bottom-up effects on
      the leafminer Tuta absoluta.
AB  - This study examined the effects of various levels of nitrogen inputs (optimal,
      insufficient and excessive) and water inputs (optimal, low drought and high
      drought) to tomato plants (Solanum lycopersicum) on survival and development of
      an invasive tomato leafminer, Tuta absoluta (Meytick) (Lepidoptera: Gelechiidae).
      Plant growth i.e. plant height and the number of nodes declined under
      insufficient or excessive nitrogen treatment. Compared to optimal N, insufficient
      N treatment decreased leaf N content and increased the carbon/nitrogen ratio
      (C/N) whereas an excess of N had no effect on both leaf N content and leaf C/N
      ratio. Sub-optimal nitrogen supplies, water treatments and their interactions,
      significantly reduced the leafminer survival rate and slowed down its
      development. Together with the findings from three recent companion studies, we
      assumed that a combination of changes in nutritional value and chemical defense
      could explain these observed effects. Furthermore, our findings supported both
      the "Plant vigor hypothesis" and the "Nitrogen limitation hypothesis". 

PMID- 24675798
TI  - Recent developments in solid-state NMR spectroscopy of crystalline microporous
      materials.
AB  - Microporous materials, having pores and channels on the same size scale as small
      to medium molecules, have found many important applications in current
      technologies, including catalysis, gas separation and drug storage and delivery.
      Many of their properties and functions are related to their detailed local
      structure, such as the type and distribution of active sites within the pores,
      and the specific structures of these active sites. Solid-state NMR spectroscopy
      has a strong track record of providing the requisite detailed atomic-level
      insight into the structures of microporous materials, in addition to being able
      to probe dynamic processes occurring on timescales spanning many orders of
      magnitude (i.e., from s to ps). In this Perspective, we provide a brief review of
      some of the basic experimental approaches used in solid-state NMR spectroscopy of
      microporous materials, and then discuss some more recent advances in this field,
      particularly those applied to the study of crystalline materials such as zeolites
      and metal-organic frameworks. These advances include improved software for aiding
      spectral interpretation, the development of the NMR-crystallography approach to
      structure determination, new routes for the synthesis of isotopically-labelled
      materials, methods for the characterisation of host-guest interactions, and
      methodologies suitable for observing NMR spectra of paramagnetic microporous
      materials. Finally, we discuss possible future directions, which we believe will
      have the greatest impact on the field over the coming years. 

PMID- 24675797
TI  - Metabolic and target-site mechanisms combine to confer strong DDT resistance in
      Anopheles gambiae.
AB  - The development of resistance to insecticides has become a classic exemplar of
      evolution occurring within human time scales. In this study we demonstrate how
      resistance to DDT in the major African malaria vector Anopheles gambiae is a
      result of both target-site resistance mechanisms that have introgressed between
      incipient species (the M- and S-molecular forms) and allelic variants in a DDT
      detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT
      resistant and susceptible strains of An. gambiae, revealed a non-synonymous
      polymorphism (I114T), proximal to the DDT binding domain, which segregated with
      strain phenotype. Recombinant protein expression and DDT metabolism analysis
      revealed that the proteins from the susceptible strain lost activity at higher
      DDT concentrations, characteristic of substrate inhibition. The effect of I114T
      on GSTE2 protein structure was explored through X-ray crystallography. The amino
      acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the
      hydrophobic DDT-binding region. The exchange does not result in structural
      alterations but is predicted to facilitate local dynamics and enzyme activity.
      Expression of both wild-type and 114T alleles the allele in Drosophila conferred
      an increase in DDT tolerance. The 114T mutation was significantly associated with
      DDT resistance in wild caught M-form populations and acts in concert with target
      site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to
      confer extreme levels of DDT resistance in wild caught An. gambiae. 

PMID- 24675799
TI  - Synthesis and characterisation of the complete series of B-N analogues of
      triptycene.
AB  - The reaction between the bisborate Li2[o-C6H4(BH3)2] and 2 equivalents of an
      appropriate pyrazole derivative (Hpz(R)) in the presence of Me3SiCl yields o
      phenylene-bridged pyrazaboles HB(MU-pz(R))2(MU-o-C6H4)BH (3a-3e; Hpz(R) = 4
      iodopyrazole (3a), 4-(trimethylsilyl)pyrazole (3b), 3,5-dimethylpyrazole (3c),
      3,5-di(tert-butyl)pyrazole (3d), 3,5-bis(trifluoromethyl)pyrazole (3e)). The
      synthesis approach thus provides access to uncharged B-N triptycenes bearing (i)
      functionalisable groups, (ii) electron-donating or -withdrawing substituents and
      (iii) pyrazole rings of varying steric demand. Treatment of p-R*C6H4BBr2 with the
      potassium tris(pyrazol-1-yl)borates K[HBpz3] or K[p-R*C6H4Bpz3] yields cationic
      pyrazolyl-bridged pyrazaboles [p-BrC6H4B(MU-pz)3BH]Br ([4a]Br) and [p-R*C6H4B(MU
      pz)3Bp-C6H4R*]Br (R* = Br ([4b]Br), I ([4c]Br), SiMe3 ([4d]Br)), which can be
      regarded as full B-N analogues of triptycene. The B-H bonds of 3b and [4a]Br are
      unreactive towards tBuC[triple bond, length as m-dash]CH even at temperatures of
      80  degrees C, thereby indicating an appreciable thermal stability of the
      corresponding B-N cage bonds. Most of the cage compounds are sufficiently inert
      towards water to allow quick aqueous workup. However, NMR spectroscopy in CD3OD
      solution reveals degradation of 3b or [4a]Br to the corresponding pyrazoles and o
      C6H4(B(OCD3)2)2 or p-BrC6H4B(OCD3)2/B(OCD3)3. The diphenylated species [4b]Br is
      significantly more stable under the same measurement conditions; even after 76 d,
      most of the material degrades only to the stage of the syn/anti-pyrazaboles p
      BrC6H4(CD3O)B(MU-pz)2B(OCD3)p-C6H4Br (11a/11b). A derivatisation of [4c]Br with
      nBu3SnC=CtBu through Stille-type coupling reactions furnishes the alkynyl
      derivative [p-tBuC=CC6H4B(MU-pz)3Bp-C6H4C=CtBu]Br ([4e]Br). Larger B-N aggregates
      are also accessible: treatment of the tetrakisborate Li4[1,2,4,5-C6H2(BH3)4] with
      4 equivalents of Hpz(R) in the presence of Me3SiCl leads to the corresponding B-N
      pentiptycenes (Hpz(R) = 3,5-bis(trifluoromethyl)pyrazole (14a), 4
      (trimethylsilyl)pyrazole (14b), 3,5-dimethylpyrazole (14c), 3,5-di(tert
      butyl)pyrazole (14d)).

PMID- 24675800
TI  - Pituitary apoplexy syndrome as the manifestation of intracranial tuberculoma.
AB  - Pituitary apoplexy syndrome is characterised by acute neuro-ophthalmological
      features and usually occurs due to bleeding in a pituitary adenoma. It is an
      unusual presentation of tuberculoma, as only few similar cases have been reported
      previously. A 17-year-old girl presented with headache, vomiting, altered
      sensorium and vision loss. MRI of the brain revealed ring enhancing sellar
      lesions with other enhancing lesions and leptomeningeal enhancement.
      Cerebrospinal fluid microscopy, biochemistry and PCR for tuberculosis confirmed
      tubercular meningitis. The patient was treated with antituberculous therapy and
      was asymptomatic at the end of treatment. 

PMID- 24675801
TI  - Bilateral perinatal arterial stroke in a neonate.

PMID- 24675802
TI  - Hormone dependency in metastatic low-grade leiomyosarcoma following uterine
      smooth muscle tumour of uncertain malignant potential.
AB  - Uterine leiomyosarcoma (ULMS) usually follows an aggressive clinical course,
      although a small proportion of ULMS exhibit a more indolent course, which in turn
      reflects heterogeneity within this disease and the need to identify and
      characterise this distinct subgroup. The role of hormone therapy in ULMS is yet
      to be elucidated. We report a patient with well-differentiated metastatic ULMS on
      hormone replacement therapy (HRT) at the time of the diagnosis. The withdrawal of
      the HRT led to a significant decrease in the tumour burden and symptomatic
      improvement. The patient further benefited from aromatase inhibitor treatment
      once the benefit from the HRT withdrawal reached a plateau. The present case
      report describes for the first time hormone-dependency for tumour growth in a
      ULMS. We propose that a subset of ULMS that follow a protracted/indolent course
      might depend on hormone stimulation for tumour proliferation, and antihormone
      treatment can therefore be useful in these patients. 

PMID- 24675803
TI  - Carotid stent infection: a rare but potentially fatal complication of carotid
      artery stenting.
AB  - Infections involving endovascular devices are rare and, to our knowledge, only
      three cases of infection with an inserted carotid stent have ever been reported.
      A 68-year-old man underwent carotid artery stenting (CAS) of the left proximal
      internal carotid artery. Two days after CAS the patient developed a high fever
      and investigation showed that the inserted carotid stent was infected. The
      infection could not be controlled despite adequate antibiotic therapy. Eventually
      a rupture of the carotid artery occurred and the patient underwent emergency
      resection of the left carotid bifurcation in addition to stent removal and
      reconstruction with a saphenous vein interposition graft. The patient recovered
      fully without any neurological sequelae. 

PMID- 24675804
TI  - Age-related changes in the cellular composition and epithelial organization of
      the mouse trachea.
AB  - We report here senescent changes in the structure and organization of the
      mucociliary pseudostratified epithelium of the mouse trachea and main stem
      bronchi. We confirm previous reports of the gradual appearance of age-related,
      gland-like structures (ARGLS) in the submucosa, especially in the intercartilage
      regions and carina. Immunohistochemistry shows these structures contain ciliated
      and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or
      ciliated ducts typical of normal submucosal glands. Data suggest they arise de
      novo by budding from the surface epithelium rather than by delayed growth of
      rudimentary or cryptic submucosal glands. In old mice the surface epithelium
      contains fewer cells per unit length than in young mice and the proportion of
      Krt5+, p63+ basal cells is reduced in both males and females. However, there
      appears to be no significant difference in the ability of basal stem cells
      isolated from individual young and old mice to form clonal tracheospheres in
      culture or in the ability of the epithelium to repair after damage by inhaled
      sulfur dioxide. Gene expression analysis by Affymetrix microarray and
      quantitative PCR, as well as immunohistochemistry and flow sorting studies, are
      consistent with low-grade chronic inflammation in the tracheas of old versus
      young mice and an increase in the number of immune cells. The significance of
      these changes for ARGL formation are not clear since several treatments that
      induce acute inflammation in young mice did not result in budding of the surface
      epithelium. 

PMID- 24675805
TI  - New insights into how Yersinia pestis adapts to its mammalian host during bubonic
      plague.
AB  - Bubonic plague (a fatal, flea-transmitted disease) remains an international
      public health concern. Although our understanding of the pathogenesis of bubonic
      plague has improved significantly over the last few decades, researchers have
      still not been able to define the complete set of Y. pestis genes needed for
      disease or to characterize the mechanisms that enable infection. Here, we
      generated a library of Y. pestis mutants, each lacking one or more of the genes
      previously identified as being up-regulated in vivo. We then screened the library
      for attenuated virulence in rodent models of bubonic plague. Importantly, we
      tested mutants both individually and using a novel, "per-pool" screening method
      that we have developed. Our data showed that in addition to genes involved in
      physiological adaptation and resistance to the stress generated by the host,
      several previously uncharacterized genes are required for virulence. One of these
      genes (ympt1.66c, which encodes a putative helicase) has been acquired by
      horizontal gene transfer. Deletion of ympt1.66c reduced Y. pestis' ability to
      spread to the lymph nodes draining the dermal inoculation site--probably because
      loss of this gene decreased the bacteria's ability to survive inside macrophages.
      Our results suggest that (i) intracellular survival during the early stage of
      infection is important for plague and (ii) horizontal gene transfer was crucial
      in the acquisition of this ability.

PMID- 24675806
TI  - Tumor lysing genetically engineered T cells loaded with multi-modal imaging
      agents.
AB  - Genetically-modified T cells expressing chimeric antigen receptors (CAR) exert
      anti-tumor effect by identifying tumor-associated antigen (TAA), independent of
      major histocompatibility complex. For maximal efficacy and safety of adoptively
      transferred cells, imaging their biodistribution is critical. This will determine
      if cells home to the tumor and assist in moderating cell dose. Here, T cells are
      modified to express CAR. An efficient, non-toxic process with potential for cGMP
      compliance is developed for loading high cell number with multi-modal (PET-MRI)
      contrast agents (Super Paramagnetic Iron Oxide Nanoparticles - Copper-64; SPION
      (64)Cu). This can now be potentially used for (64)Cu-based whole-body PET to
      detect T cell accumulation region with high-sensitivity, followed by SPION-based
      MRI of these regions for high-resolution anatomically correlated images of T
      cells. CD19-specific-CAR(+)SPION(pos) T cells effectively target in vitro CD19(+)
      lymphoma. 

PMID- 24675807
TI  - Clinical, radiological and ultrasonographic findings related to knee pain in
      osteoarthritis.
AB  - BACKGROUND: Pain is the predominant symptom of knee osteoarthritis (OA) and the
      main reason of disability. Ultrasound is now one of the new imaging modality in
      Musculoskeletal medicine and its role in assessing the pain severity in the knee
      osteoarthritis is evaluated in this study. OBJECTIVES: (1) To study the
      correlation between ultrasonographic (US) findings and pain score and (2) whether
      ultrasonographic findings show a better association of pain level than
      conventional X-rays in patients suffering from primary knee osteoarthritis.
      METHODS: In this multi-center study, 193 patients with primary knee OA were asked
      to score their average knee pain using the Western Ontario and McMaster
      Universities Arthritis (WOMAC) questionnaire;patients would then go for a
      radiological and an US evaluation of their painful knee. Findings from both
      imaging modalities will be studied with the associated pain score. RESULTS:
      Ultrasound showed that knee effusion has positive correlation with pain score
      upon walking (r = 0.217) and stair climbing (r = 0.194). Presence of
      suprapatellar synovitis had higher pain score on sitting (Spearman's Rank
      correlation  = 0.355). The medial(r = 0.170) and lateral meniscus protrusion (r =
      0.201) were associated with pain score upon stair climbing. CONCLUSIONS: Our
      study found that both imaging modalities shown some significant association with
      the aspect of pain; neither one is clearly better but rather complementary to
      each other. A trend is found in both modalities: walking pain is related to
      pathologies of the either the lateral or medial tibiofemoral joint(TFJ)while
      stair climbing pain is related to both tibiofemoral joint pathologies and also to
      the patellofemoral joint (PFJ) pathology. This suggested that biomechanical
      derangement is an important aspect in OA knee pain.

PMID- 24675809
TI  - On the upconversion fluorescence in carbon nanodots and graphene quantum dots.
AB  - Upconversion fluorescence has been frequently cited as an important feature in
      carbon nanodots (CNDs) and graphene quantum dots (GQDs); and some mechanisms and
      potential applications have been proposed. Contrary to such a general belief, we
      demonstrate in this report no observable upconversion fluorescence based on five
      different synthesized CNDs and GQDs. We confirm that the so-called upconversion
      fluorescence actually originates from the normal fluorescence excited by the
      leaking component from the second diffraction in the monochromator of the
      fluorescence spectrophotometer. Upconversion fluorescence can be identified by
      measuring the excitation intensity dependence of the fluorescence. 

PMID- 24675808
TI  - Expression microarray analysis reveals alternative splicing of LAMA3 and DST
      genes in head and neck squamous cell carcinoma.
AB  - PURPOSE: Prior studies have demonstrated tumor-specific alternative splicing
      events in various solid tumor types. The role of alternative splicing in the
      development and progression of head and neck squamous cell carcinoma (HNSCC) is
      unclear. Our study queried exon-level expression to implicate splice variants in
      HNSCC tumors. EXPERIMENTAL DESIGN: We performed a comparative genome-wide
      analysis of 44 HNSCC tumors and 25 uvulopalatopharyngoplasty (UPPP) tissue
      samples at an exon expression level. In our comparison we ranked genes based upon
      a novel score-the Maximum-Minimum Exon Score (MMES)--designed to predict the
      likelihood of an alternative splicing event occurring. We validated predicted
      alternative splicing events using quantitative RT-PCR on an independent cohort.
      RESULTS: After MMES scoring of 17,422 genes, the top 900 genes with the highest
      scores underwent additional manual inspection of expression patterns in a
      graphical analysis. The genes LAMA3, DST, VEGFC, SDHA, RASIP1, and TP63 were
      selected for further validation studies because of a high frequency of
      alternative splicing suggested in our graphical analysis, and literature review
      showing their biological relevance and known splicing patterns. We confirmed TP63
      as having dominant expression of the short DeltaNp63 isoform in HNSCC tumor
      samples, consistent with prior reports. Two of the six genes (LAMA3 and DST)
      validated by quantitative RT-PCR for tumor-specific alternative splicing events
      (Student's t test, P<0.001). CONCLUSION: Alternative splicing events of
      oncologically relevant proteins occur in HNSCC. The number of genes expressing
      tumor-specific splice variants needs further elucidation, as does the functional
      significance of selective isoform expression.

PMID- 24675812
TI  - Solution-processed flexible transparent conductors based on carbon nanotubes and
      silver grid hybrid films.
AB  - In a simple, cost-effective, and solution-based process, a thin-film of single
      walled carbon nanotubes is hybridized on a PET film which has been patterned with
      solution self-assembled Ag nanoparticles. Such a flexible and transparent
      electrode exhibits a sheet resistance down to ~5.8 Omega sq(-1) at ~83.7% optical
      transmittance. The hybrid films are stable under ambient conditions and offer
      excellent bendability. 

PMID- 24675810
TI  - Viral quasispecies assembly via maximal clique enumeration.
AB  - Virus populations can display high genetic diversity within individual hosts. The
      intra-host collection of viral haplotypes, called viral quasispecies, is an
      important determinant of virulence, pathogenesis, and treatment outcome. We
      present HaploClique, a computational approach to reconstruct the structure of a
      viral quasispecies from next-generation sequencing data as obtained from bulk
      sequencing of mixed virus samples. We develop a statistical model for paired-end
      reads accounting for mutations, insertions, and deletions. Using an iterative
      maximal clique enumeration approach, read pairs are assembled into haplotypes of
      increasing length, eventually enabling global haplotype assembly. The performance
      of our quasispecies assembly method is assessed on simulated data for varying
      population characteristics and sequencing technology parameters. Owing to its
      paired-end handling, HaploClique compares favorably to state-of-the-art haplotype
      inference methods. It can reconstruct error-free full-length haplotypes from low
      coverage samples and detect large insertions and deletions at low frequencies. We
      applied HaploClique to sequencing data derived from a clinical hepatitis C virus
      population of an infected patient and discovered a novel deletion of length 357+/
      167 bp that was validated by two independent long-read sequencing experiments.
      HaploClique is available at https://github.com/armintoepfer/haploclique. A
      summary of this paper appears in the proceedings of the RECOMB 2014 conference,
      April 2-5. 

PMID- 24675813
TI  - Experimental Evidence for Minorities' Hesitancy in Reporting Their Opinions: The
      Roles of Optimal Distinctiveness Needs and Normative Influence.
AB  - Four experiments provided evidence for when and why opinion minorities take more
      time than opinion majorities to report their opinions. In Study 1, participants
      who wrote about feeling overly different from-but not overly similar to-others
      were slower to report their opinions after being led to believe that they held a
      minority than majority opinion. In Studies 2 and 3, minority opinion holders'
      hesitancy was attenuated among participants with a high dispositional need for
      uniqueness, and this effect was mediated by low need for uniqueness individuals'
      beliefs that their minority opinions were less normative than their majority
      opinions (Study 3). In Study 4, a subtle need to belong manipulation amplified
      the differences in response times between opinion minorities and majorities.
      Together, these studies show that minorities' hesitancy in reporting their
      opinions depends on their motives to belong versus be unique and stems from
      normative influence processes.

PMID- 24675811
TI  - The membrane-associated transcription factor NAC089 controls ER-stress-induced
      programmed cell death in plants.
AB  - The unfolded protein response (UPR) is activated to sustain cell survival by
      reducing misfolded protein accumulation in the endoplasmic reticulum (ER). The
      UPR also promotes programmed cell death (PCD) when the ER stress is severe;
      however, the underlying molecular mechanisms are less understood, especially in
      plants. Previously, two membrane-associated transcriptions factors (MTFs), bZIP28
      and bZIP60, were identified as the key regulators for cell survival in the plant
      ER stress response. Here, we report the identification of another MTF, NAC089, as
      an important PCD regulator in Arabidopsis (Arabidopsis thaliana) plants. NAC089
      relocates from the ER membrane to the nucleus under ER stress conditions.
      Inducible expression of a truncated form of NAC089, in which the transmembrane
      domain is deleted, induces PCD with increased caspase 3/7-like activity and DNA
      fragmentation. Knock-down NAC089 in Arabidopsis confers ER stress tolerance and
      impairs ER-stress-induced caspase-like activity. Transcriptional regulation
      analysis and ChIP-qPCR reveal that NAC089 plays important role in regulating
      downstream genes involved in PCD, such as NAC094, MC5 and BAG6. Furthermore,
      NAC089 is up-regulated by ER stress, which is directly controlled by bZIP28 and
      bZIP60. These results show that nuclear relocation of NAC089 promotes ER-stress
      induced PCD, and both pro-survival and pro-death signals are elicited by bZIP28
      and bZIP60 during plant ER stress response. 

PMID- 24675814
TI  - Cyclin D1 overexpression is associated with poor clinicopathological outcome and
      survival in oral squamous cell carcinoma in Asian populations: insights from a
      meta-analysis.
AB  - BACKGROUND: The clinicopathological significance of cyclin D1 overexpression and
      prognosis of oral squamous cell carcinoma has not been fully quantified. We
      performed a comprehensive meta-analysis for evaluation of cyclin D1
      overexpression in oral squamous cell carcinoma to determine the strength of this
      association. METHODS: Using both medical subheadings and free terms, we searched
      PubMed, Embase and the Institute for Scientific Information Web of Science for
      all eligible studies published before Nov. 2013. We retrieved 1674 citations,
      determining that 15 met the selection criteria. We used the odds ratio (OR) and
      hazard ratio (HR) as the common measures of association to quantitatively
      determine the correlation between cyclin D1 overexpression and outcomes of oral
      cancer. We performed a meta-analysis and heterogeneity, sensitivity, and subgroup
      analyses to clarify and validate the pooled results. RESULTS: The pooled results
      provided compelling evidence that cyclin D1 overexpression was significantly
      correlated with increased tumor size (OR = 1.617, 95% confidence interval [CI] =
      1.046-2.498, p = 0.031), lymphoid node metastasis (OR = 2.035, 95% CI = 1.572
      2.635, p<0.001), tumor differentiation (OR = 1.976, 95% CI = 1.363-2.866,
      p<0.001), and advancement of clinical stages (OR = 1.516, 95% CI = 1.140-2.015, p
      = 0.004), and adversely influenced overall survival of OSCC patients (HR = 1.897,
      95% CI = 1.577-2.282, p<0.001). The strength of association varied in different
      oral cavity subsites. CONCLUSION: Our findings indicated that cyclin D1
      expression correlates with detrimental clinicopathological outcome and poor
      prognosis in oral squamous cell carcinoma. Our results may be useful in the
      management of oral cancer.

PMID- 24675815
TI  - Auditory and visual sustained attention in children with speech sound disorder.
AB  - Although research has demonstrated that children with specific language
      impairment (SLI) and reading disorder (RD) exhibit sustained attention deficits,
      no study has investigated sustained attention in children with speech sound
      disorder (SSD). Given the overlap of symptoms, such as phonological memory
      deficits, between these different language disorders (i.e., SLI, SSD and RD) and
      the relationships between working memory, attention and language processing, it
      is worthwhile to investigate whether deficits in sustained attention also occur
      in children with SSD. A total of 55 children (18 diagnosed with SSD (8.11 +/-
      1.231) and 37 typically developing children (8.76 +/- 1.461)) were invited to
      participate in this study. Auditory and visual sustained-attention tasks were
      applied. Children with SSD performed worse on these tasks; they committed a
      greater number of auditory false alarms and exhibited a significant decline in
      performance over the course of the auditory detection task. The extent to which
      performance is related to auditory perceptual difficulties and probable working
      memory deficits is discussed. Further studies are needed to better understand the
      specific nature of these deficits and their clinical implications.

PMID- 24675816
TI  - Prior experience but not size of error improves motor learning on the split-belt
      treadmill in young children.
AB  - Children can modify learned motor skills, such as walking, to adapt to new
      environments. Movement errors in these new situations drive the learning. We used
      split-belt walking to determine whether size of the error affects the degree of
      learning. Twenty-two children (aged 2-5 y) walked on the split-belt treadmill on
      two separate days spaced 1 week apart. Twenty-eight adults served as controls. On
      Day 1, children experienced an abrupt change in belt speeds (from 1:1 to 2:1
      differential) resulting in large errors, or a gradual change (same change in
      speed over 12-15 min), resulting in small errors. Learning was measured by the
      size of the aftereffect upon return to a 1:1 differential. On Day 2 (1 week
      later), the leg on the fast belt was reversed, as was the method of introducing
      the speed differential. We found that the error size did not affect learning.
      Unexpectedly, learning was greater on Day 2 compared to Day 1, especially for
      children under 4 y of age, despite the fact that the task was opposite to that of
      Day 1, and did not influence learning in adults. Hence, 11 additional children
      under 4 y of age were tested with belts running at the same speed on Day 1, and
      with a 2:1 speed differential (abrupt introduction) on Day 2. Surprisingly,
      learning was again greater on Day 2. We conclude that size of error during split
      belt walking does not affect learning, but experience on a treadmill does,
      especially for younger children.

PMID- 24675818
TI  - Chinese Grain for Green Program led to highly increased soil organic carbon
      levels: a meta-analysis.
AB  - The Grain for Green Program (GGP), initiated in 1999, is the largest ecological
      restoration project in central and western China. Here, for the first time, we
      performed a meta-analysis and found that the GGP largely increased the soil
      organic carbon (SOC). The SOC was increased by 48.1%, 25.4%, and 25.5% at soil
      depths of 0-20 cm, 20-40 cm, and 40-60 cm, respectively. Moreover, this carbon
      accumulation has significantly increased over time since GGP implementation. The
      carbon accumulation showed a significantly more active response to the GGP in the
      top 20 cm of soil than in the deeper soil layers. Conversion of cropland to
      forest could lead to significantly greater SOC accumulation than would the
      conversion of cropland to grassland. Conversion from cropland to woodland could
      lead to greater SOC accumulation than would the conversion to either shrubland or
      orchard. Our results suggest that the GGP implementation caused SOC to accumulate
      and that there remains a large potential for further accumulation of carbon in
      the soil, which will help to mitigate climate change in the near future.

PMID- 24675817
TI  - Role of the protein tyrosine phosphatase Shp2 in homeostasis of the intestinal
      epithelium.
AB  - Protein tyrosine phosphorylation is thought to be important for regulation of the
      proliferation, differentiation, and rapid turnover of intestinal epithelial cells
      (IECs). The role of protein tyrosine phosphatases in such homeostatic regulation
      of IECs has remained largely unknown, however. Src homology 2-containing protein
      tyrosine phosphatase (Shp2) is a ubiquitously expressed cytoplasmic protein
      tyrosine phosphatase that functions as a positive regulator of the Ras-mitogen
      activated protein kinase (MAPK) signaling pathway operative downstream of the
      receptors for various growth factors and cytokines, and it is thereby thought to
      contribute to the regulation of cell proliferation and differentiation. We now
      show that mice lacking Shp2 specifically in IECs (Shp2 CKO mice) develop severe
      colitis and die as early as 3 to 4 weeks after birth. The number of goblet cells
      in both the small intestine and colon of Shp2 CKO mice was markedly reduced
      compared with that for control mice. Furthermore, Shp2 CKO mice showed marked
      impairment of both IEC migration along the crypt-villus axis in the small
      intestine and the development of intestinal organoids from isolated crypts. The
      colitis as well as the reduction in the number of goblet cells apparent in Shp2
      CKO mice were normalized by expression of an activated form of K-Ras in IECs. Our
      results thus suggest that Shp2 regulates IEC homeostasis through activation of
      Ras and thereby protects against the development of colitis. 

PMID- 24675819
TI  - P-chiral phosphorus heterocycles: a straightforward synthesis.
AB  - A straightforward synthesis of P-chiral polycyclic 7-phospha-norbornenes via an
      asymmetric Diels-Alder reaction is presented. The employed starting materials are
      cheap, easily accessible and of structural diversity facilitating a new flexible
      route towards differently functionalised P-chiral phosphanes. 

PMID- 24675820
TI  - Highly efficient and autocatalytic H22 dissociation for CO2 reduction into formic
      acid with zinc.
AB  - Artificial photosynthesis, specifically H2O dissociation for CO2 reduction with
      solar energy, is regarded as one of the most promising methods for sustainable
      energy and utilisation of environmental resources. However, a highly efficient
      conversion still remains extremely challenging. The hydrogenation of CO2 is
      regarded as the most commercially feasible method, but this method requires
      either exotic catalysts or high-purity hydrogen and hydrogen storage, which are
      regarded as an energy-intensive process. Here we report a highly efficient method
      of H2O dissociation for reducing CO2 into chemicals with Zn powder that produces
      formic acid with a high yield of approximately 80%, and this reaction is revealed
      for the first time as an autocatalytic process in which an active intermediate,
      ZnH(-) complex, serves as the active hydrogen. The proposed process can assist in
      developing a new concept for improving artificial photosynthetic efficiency by
      coupling geochemistry, specifically the metal-based reduction of H2O and CO2,
      with solar-driven thermochemistry for reducing metal oxide into metal. 

PMID- 24675821
TI  - Reply to the 'Comment on "Density functional theory analysis of structural and
      electronic properties of orthorhombic perovskite CH3NH3PbI3"' by J. Even et al.,
      Phys. Chem. Chem. Phys., 2014, 10.1039/C3CP55006K.
AB  - Perovskite CH3NH3PbI3 materials were theoretically investigated using density
      functional theory (DFT) since they are an important component in novel perovskite
      based solar cells. One of the challenges is to accurately describe their
      electronic structures. As stated in our original paper, the accidental agreement
      of band gap energies between the traditional DFT calculations and the
      experimental measurement is "fortuitous". The disadvantage of traditional DFT can
      be partially solved by the recent progress made by Even et al. with the
      consideration of spin-orbit coupling and many-body self-energy corrections.
      However, the C-N bonding mechanisms in CH3NH3(+) cations cannot be deduced from
      the Bader charge analysis. 

PMID- 24675822
TI  - Insight into the karyotype evolution of brachypodium species using comparative
      chromosome barcoding.
AB  - Paleogenomic studies based on bioinformatic analyses of DNA sequences have
      enabled unprecedented insight into the evolution of grass genomes. They have
      revealed that nested chromosome fusions played an important role in the
      divergence of modern grasses. Nowadays, studies on karyotype evolution based on
      the sequence analysis can also be effectively complemented by the fine-scale
      cytomolecular approach. In this work, we studied the karyotype evolution of small
      genome grasses using BAC-FISH based comparative chromosome barcoding in four
      Brachypodium species: diploid B. distachyon (2n = 10) and B. sylvaticum (2n =
      18), diploid (2n = 18) and allopolyploid (2n = 28) B. pinnatum as well as B.
      phoenicoides (2n = 28). Using BAC clones derived from the B. distachyon genomic
      libraries for the chromosomes Bd2 and Bd3, we identified the descending dysploidy
      events that were common for diploids with x = 9 and B. distachyon as well as two
      nested chromosome fusions that were specific only for B. distachyon. We suggest
      that dysploidy events that are shared by different lineages of the genus had
      already appeared in their common ancestor. We also show that additional
      structural rearrangements, such as translocations and duplications, contributed
      to increasing genome diversification in the species analysed. No chromosomes
      structured exactly like Bd2 and Bd3 were found in B. pinnatum (2n = 28) and B.
      phoenicoides. The structure of Bd2 and Bd3 homeologues belonging to the two
      genomes in the allopolyploids resembled the structure of their counterparts in
      the 2n = 18 diploids. These findings reinforce the hypothesis which excludes B.
      distachyon as a potential parent for Eurasian perennial Brachypodium
      allopolyploids. Our cytomolecular data elucidate some mechanisms of the
      descending dysploidy in monocots and enable reconstructions of the evolutionary
      events which shaped the extant karyotypes in both the genus Brachypodium and in
      grasses as a whole.

PMID- 24675824
TI  - Crossing borders for science.
AB  - Exchanging ideas with like-minded, enthusiastic people interested in the same
      topic is crucial for the advancement of a scientist's career. Several Regional
      Student Groups (RSGs) of the International Society for Computational Biology
      (ISCB) Student Council have cooperated in the last six years to organize
      scientific workshops and conferences. With motivated students, it is possible to
      create a memorable event for fellow scientists; in doing so, the organizers gain
      valuable experiences. While collaborating across borders and time zones can be
      difficult, feedback from event organizers was always positive. When limited
      resources are juxtaposed with great ideas and a network of contacts, the outcome
      is always an amazing experience, despite organizers being separated
      geographically across different countries. 

PMID- 24675823
TI  - An immunomics approach to schistosome antigen discovery: antibody signatures of
      naturally resistant and chronically infected individuals from endemic areas.
AB  - Schistosomiasis is a neglected tropical disease that is responsible for almost
      300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the
      control of schistosomiasis, but chemotherapy fails to prevent reinfection with
      schistosomes, so MDA alone is not sufficient to eliminate the disease, and a
      prophylactic vaccine is required. Herein, we take advantage of recent advances in
      systems biology and longitudinal studies in schistosomiasis endemic areas in
      Brazil to pilot an immunomics approach to the discovery of schistosomiasis
      vaccine antigens. We selected mostly surface-derived proteins, produced them
      using an in vitro rapid translation system and then printed them to generate the
      first protein microarray for a multi-cellular pathogen. Using well-established
      Brazilian cohorts of putatively resistant (PR) and chronically infected (CI)
      individuals stratified by the intensity of their S. mansoni infection, we probed
      arrays for IgG subclass and IgE responses to these antigens to detect antibody
      signatures that were reflective of protective vs. non-protective immune
      responses. Moreover, probing for IgE responses allowed us to identify antigens
      that might induce potentially deleterious hypersensitivity responses if used as
      subunit vaccines in endemic populations. Using multi-dimensional cluster analysis
      we showed that PR individuals mounted a distinct and robust IgG1 response to a
      small set of newly discovered and well-characterized surface (tegument) antigens
      in contrast to CI individuals who mounted strong IgE and IgG4 responses to many
      antigens. Herein, we show the utility of a vaccinomics approach that profiles
      antibody responses of resistant individuals in a high-throughput multiplex
      approach for the identification of several potentially protective and safe
      schistosomiasis vaccine antigens. 

PMID- 24675826
TI  - Organometallic and coordination chemistry of carbon nanomaterials.

PMID- 24675825
TI  - Cause-specific mortality according to urine albumin creatinine ratio in the
      general population.
AB  - BACKGROUND: Urine albumin creatinine ratio, UACR, is positively associated with
      all-cause mortality, cardiovascular disease and diabetes in observational
      studies. Whether a high UACR is also associated with other causes of death is
      unclear. We investigated the association between UACR and cause-specific
      mortality. METHODS: We included a total of 9,125 individuals from two population
      based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001,
      respectively. Urine albumin creatinine ratio was measured from spot urine samples
      by standard methods. Information on causes of death was obtained from The Danish
      Register of Causes of Death until 31 December 2010. There were a total of 920
      deaths, and the median follow-up was 11.3 years. RESULTS: Multivariable Cox
      regression analyses with age as underlying time axis showed statistically
      significant positive associations between UACR status and risk of all-cause
      mortality, endocrine nutritional and metabolic diseases, mental and behavioural
      disorders, diseases of the circulatory system, and diseases of the respiratory
      system with hazard ratios 1.56, 6.98, 2.34, 2.03, and 1.91, for the fourth UACR
      compared with the first, respectively. Using UACR as a continuous variable, we
      also found a statistically significant positive association with risk of death
      caused by diseases of the digestive system with a hazard ratio of 1.02 per 10
      mg/g higher UACR. CONCLUSION: We found statistically significant positive
      associations between baseline UACR and death from all-cause mortality, endocrine
      nutritional and metabolic diseases, and diseases of the circulatory system and
      possibly mental and behavioural disorders, and diseases of the respiratory and
      digestive system.

PMID- 24675827
TI  - Consequences of CO2 solubility for hydrate formation from carbon dioxide
      containing water and other impurities.
AB  - Deciding on the upper bound of water content permissible in a stream of dense
      carbon dioxide under pipeline transport conditions without facing the risks of
      hydrate formation is a complex issue. In this work, we outline and analyze ten
      primary routes of hydrate formation inside a rusty pipeline, with hydrogen
      sulfide, methane, argon, and nitrogen as additional impurities. A comprehensive
      treatment of equilibrium absolute thermodynamics as applied to multiple hydrate
      phase transitions is provided. We also discuss in detail the implications of the
      Gibbs phase rule that make it necessary to consider non-equilibrium
      thermodynamics. The analysis of hydrate formation risk has been revised for the
      dominant routes, including the one traditionally considered in industrial
      practice and hydrate calculators. The application of absolute thermodynamics with
      parameters derived from atomistic simulations leads to several important
      conclusions regarding the impact of hydrogen sulfide. When present at studied
      concentrations below 5 mol%, the presence of hydrogen sulfide will only support
      the carbon-dioxide-dominated hydrate formation on the phase interface between
      liquid water and hydrate formers entering from the carbon dioxide phase. This is
      in contrast to a homogeneous hydrate nucleation and growth inside the aqueous
      solution bulk. Our case studies indicate that hydrogen sulfide at higher than 0.1
      mol% concentration in carbon dioxide can lead to growth of multiple hydrate
      phases immediately adjacent to the adsorbed water layers. We conclude that
      hydrate formation via water adsorption on rusty pipeline walls will be the
      dominant contributor to the hydrate formation risk, with initial concentration of
      hydrogen sulfide being the critical factor. 

PMID- 24675828
TI  - Effect of superovulation on uterine and serum biochemical parameters and its
      potential association with transferable embryos in Holstein dairy cows.
AB  - The objective of this study was to determine the effects of superovulation (SOV)
      on serum and uterine biochemical parameters, uterine bacteriology and cytology
      and number of transferable embryos (TE). Dairy cows were placed on a
      Presynch/CIDR Synch protocol. The SOV group was superovulated, induced in estrus,
      and inseminated, whereas the control group was induced in estrus and inseminated
      without SOV. Uterine bacteriology and cytology and uterine and serum biochemical
      parameters were measured at day 7 of the estrous cycle to start the SOV protocol,
      as well as on the day of embryo recovery (DER). The SOV group produced 7.5 +/-
      6.7 oocytes/embryos, of which 3.4 +/- 4.7 were TE. Serum urea and E2 and uterine
      Glu, CK, LDH, TP, P4 and PGFM in the control group and serum P4 and PGFM and
      uterine LDH and PGFM in the SOV group were significantly higher (p < 0.01) at DER
      than day 7. At DER, uterine urea, LDH, PGFM and TP and serum urea, LDH, PGFM, and
      P4 concentrations were higher (p < 0.01) in the SOV group than the control. There
      was no significant variation in uterine bacteriology or cytology. Overall, these
      results infer that SOV affects both serum profile and uterine secretions, and
      that these changes may influence the number of TE. 

PMID- 24675829
TI  - Accuracy of capillary blood 3-beta-hydroxybutyrate determination for the
      detection and treatment of canine diabetic ketoacidosis.
AB  - In human medicine, diagnosis of diabetic ketoacidosis (DKA) is usually based on
      measurement of capillary 3-beta-hydroxybutyrate (3-HB) with a hand held ketone
      sensor. This study was conducted to determine if measurement of capillary 3-HB
      could be useful for the diagnosis and monitoring of canine DKA. Fifteen dogs with
      diabetic ketosis and 10 with DKA were evaluated. Paired measurements of 3-HB of
      capillary and venous blood samples were analysed by the electrochemical sensor
      and reference method. Use of capillary 3-HB measurement during DKA management was
      then evaluated through simultaneous measurements of capillary 3-HB, urinary AcAc
      and venous blood gas analysis. Good agreement between capillary and venous 3-HB
      measurement was detected by the electrochemical sensor and reference method.
      Monitoring treatment of DKA revealed a significant correlation between capillary
      3-HB and acidosis markers, while no significant correlation was observed between
      AcAc and acidosis markers. A cut-off value of capillary blood 3-HB > 3.8 mmol/L
      for diagnosis of DKA resulted in 70% and 92% sensitivity and specificity. The
      electrochemical sensor accurately measures 3-HB concentration in both capillary
      and venous blood samples, is accurate in diagnosing canine DKA, and appears to
      reflect the patient's metabolic status during DKA treatment. 

PMID- 24675830
TI  - Comparable bone healing capacity of different bone graft matrices in a rabbit
      segmental defect model.
AB  - We compared the bone healing capacity of three different demineralized bone
      matrix (DBM) products applied using different carrier molecules (hyaluronic acid
      [HA] vs. carboxymethylcellulose [CMC]) or bone compositions (cortical bone vs.
      cortical bone and cancellous bone) in a rabbit segmental defect model. Overall,
      15-mm segmental defects in the left and right radiuses were created in 36 New
      Zealand White rabbits and filled with HA-based demineralized cortical bone matrix
      (DBX), CMC-based demineralized cortical bone matrix (DB) or CMC-based
      demineralized cortical bone with cancellous bone (NDDB), and the wound area was
      evaluated at 4, 8, and 12 weeks post-implantation. DBX showed significantly lower
      radiopacity, bone volume fraction, and bone mineral density than DB and NDDB
      before implantation. However, bone healing score, bone volume fraction, bone
      mineral density, and residual bone area at 4, 8, and 12 weeks post-implantation
      revealed no significant differences in bone healing capacity. Overall, three DBM
      products with different carrier molecules or bone compositions showed similar
      bone healing capacity. 

PMID- 24675832
TI  - Effects of resveratrol on the insulin signaling pathway of obese mice.
AB  - The present study was conducted to investigate the effects of resveratrol on the
      insulin signaling pathway in the liver of obese mice. To accomplish this, we
      administered resveratrol to high fat diet-induced obese mice and examined the
      levels of protein phosphorylation in the liver using an antibody array. The
      phosphorylation levels of 10 proteins were decreased in the high fat diet and
      resveratrol (HFR) fed group relative to the levels in the high fat diet (HF) fed
      group. In contrast, the phosphorylation levels of more than 20 proteins were
      increased in the HFR group when compared with the levels of proteins in the HF
      group. Specifically, the phosphorylation levels of Akt (The308, Tyr326, Ser473)
      were restored to normal by resveratrol when compared with the levels in the HF
      group. In addition, the phosphorylation levels of IRS-1 (Ser636/Ser639), PI-3K
      p85-subunit alpha/gamma (Tyr467/Tyr199), PDK1 (Ser241), GSK-3alpha (S21) and GSK
      3 (Ser9), which are involved in the insulin signaling pathway, were decreased in
      the HF group, whereas the levels were restored to normal in the HFR group.
      Overall, the results show that resveratrol restores the phosphorylation levels of
      proteins involved in the insulin signaling pathway, which were decreased by a
      high fat diet. 

PMID- 24675833
TI  - Protective efficacy of a high-growth reassortant swine H3N2 inactivated vaccine
      constructed by reverse genetic manipulation.
AB  - Novel reassortant H3N2 swine influenza viruses (SwIV) with the matrix gene from
      the 2009 H1N1 pandemic virus have been isolated in many countries as well as
      during outbreaks in multiple states in the United States, indicating that H3N2
      SwIV might be a potential threat to public health. Since southern China is the
      world's largest producer of pigs, efficient vaccines should be developed to
      prevent pigs from acquiring H3N2 subtype SwIV infections, and thus limit the
      possibility of SwIV infection at agricultural fairs. In this study, a high-growth
      reassortant virus (GD/PR8) was generated by plasmid-based reverse genetics and
      tested as a candidate inactivated vaccine. The protective efficacy of this
      vaccine was evaluated in mice by challenging them with another H3N2 SwIV isolate
      [A/Swine/Heilongjiang/1/05 (H3N2) (HLJ/05)]. Prime and booster inoculation with
      GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting antibodies
      and IgG antibodies. Complete protection of mice against H3N2 SwIV was observed,
      with significantly reduced lung lesion and viral loads in vaccine-inoculated mice
      relative to mock-vaccinated controls. These results suggest that the GD/PR8
      vaccine may serve as a promising candidate for rapid intervention of H3N2 SwIV
      outbreaks in China. 

PMID- 24675834
TI  - Development of a multiplex loop-mediated isothermal amplification assay to detect
      shiga toxin-producing Escherichia coli in cattle.
AB  - A multiplex loop-mediated isothermal amplification (mLAMP) assay was developed
      for simultaneous detection of the stx1 and stx2 genes and applied for detection
      of shiga toxin-producing Escherichia coli (STEC) in cattle farm samples. Two
      target genes were distinguished based on Tm values of 85.03 +/- 0.54 degrees C
      for stx1 and 87.47 +/- 0.35 degrees C for stx2. The mLAMP assay was specific
      (100% inclusivity and exclusivity), sensitive (with a detection limit as low as
      10 fg/MUL), and quantifiable (R2 = 0.9313). The efficacy and sensitivity were
      measured to evaluate applicability of the mLAMP assay to cattle farm samples. A
      total of 12 (12/253; 4.7%) and 17 (17/253; 6.7%) STEC O157, and 11 (11/236; 4.7%)
      non-O157 STEC strains were isolated from cattle farm samples by conventional
      selective culture, immunomagnetic separation, and PCR-based culture methods,
      respectively. The coinciding multiplex PCR and mLAMP results for the types of
      shiga toxin revealed the value of the mLAMP assay in terms of accuracy and
      rapidity for characterizing shiga toxin genes. Furthermore, the high detection
      rate of specific genes from enrichment broth samples indicates the potential
      utility of this assay as a screening method for detecting STEC in cattle farm
      samples. 

PMID- 24675835
TI  - Retrospective surveillance of metabolic parameters affecting reproductive
      performance of Japanese Black breeding cows.
AB  - This retrospective study was conducted to confirm the relationship between pre-
      and postpartum metabolic parameters and postpartum reproductive performance and
      to clarify seasonal characteristics of the metabolic parameters by using our
      metabolic profile test (MPT) database of Japanese Black breeding herds. In
      evaluation 1, MPT databases of blood samples from multiparous cows collected
      prepartum and postpartum were divided into two groups according to calving
      interval, and each MPT parameter was compared. In evaluation 2, the same MPT
      databases used in evaluation 1 were divided into two groups according to the
      sampling period. Significant differences were found in the prepartal total
      protein and postpartal gamma-glutamyltransferase in evaluation 1. In evaluation
      2, significant differences were found in the prepartal and postpartal total
      protein, albumin/globulin ratio, and glucose. Clear seasonal differences in MPT
      results emphasized the usefulness of the MPT in breeding cattle herds fed home
      pasture roughage and suggest that unsatisfactory reproductive performance during
      hot periods reflects inadequate nutritional content of the diet and possible
      reduced feed intake due to heat stress. 

PMID- 24675836
TI  - Clinical applications and characteristics of apparent diffusion coefficient maps
      for the brain of two dogs.
AB  - Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping
      are functional magnetic resonance imaging techniques for detecting water
      diffusion. DWI and the ADC map were performed for intracranial lesions in two
      dogs. In necrotizing leukoencephalitis, cavitated lesions contained a hypointense
      center with a hyperintense periphery on DWI, and hyperintense signals on the ADC
      maps. In metastatic sarcoma, masses including a necrotic region were hypointense
      with DWI, and hyperintense on the ADC map with hyperintense perilesional edema on
      DWI and ADC map. Since DWI and ADC data reflect the altered water diffusion, they
      can provide additional information at the molecular level. 

PMID- 24675837
TI  - Identification of abnormal gene expression in bovine transgenic somatic cell
      nuclear transfer embryos.
AB  - This study was conducted to investigate the expression of three genes related to
      early embryonic development in bovine transgenic cloned embryos. To accomplish
      this, development of bovine transgenic somatic cell nuclear transfer (SCNT)
      embryos was compared with non-transgenic embryos. Next, mRNA transcription of
      three specific genes (DNMT1, Hsp 70.1, and Mash2) related to early embryo
      development in transgenic SCNT embryos was compared between transgenic and non
      transgenic SCNTs, parthenogenetic embryos, and in vitro fertilization (IVF)
      embryos. Transgenic SCNT embryos showed significantly lower rates of development
      to the blastocyst stage than non-transgenic ones. To investigate normal gene
      expression, RNA was extracted from ten blastocysts derived from parthenogenesis,
      IVF, non-transgenic, and transgenic SCNT embryos and reverse-transcribed to
      synthesize cDNA. The cDNA was then subjected to PCR amplification and semi
      quantified. More DNMT1 mRNA was detected in the transgenic SCNT group than the
      other three groups. Hsp 70.1 mRNA was detected in the IVF embryos, while lower
      levels were found in SCNT and parthenogenetic embryos. Mash2 mRNA was present at
      the highest levels in transgenic SCNT embryos. In conclusion, the higher levels
      of methylation and lower protein synthesis after heat shock in the transgenic
      SCNT embryos expected based on our results may cause lower embryonic development.

PMID- 24675838
TI  - Enhancing mucosal immunity in mice by recombinant adenovirus expressing major
      epitopes of porcine circovirus-2 capsid protein delivered with cytosine-phosphate
      guanosine oligodeoxynucleotides.
AB  - A recombinant replication-defective adenovirus expressing the major epitopes of
      porcine circovirus-2 (PCV-2) capsid protein (rAd/Cap/518) was previously
      constructed and shown to induce mucosal immunity in mice following intranasal
      delivery. In the present study, immune responses induced by intranasal
      immunization with a combination of rAd/Cap/518 and cytosine-phosphate-guanosine
      oligodeoxynucleotides (CpG ODN) were evaluated in mice. The levels of PCV-2
      specific IgG in serum and IgA in saliva, lung, and intestinal fluids were
      significantly higher in the group immunized with rAd/Cap/518 and CpG ODN than
      animals immunized with rAd/Cap/518 alone. The frequencies of IL-2-secreting CD4+
      T cells and IFN-gamma-producing CD8+ T cells were significantly higher in the
      combined immunization group than mice immunized with rAd/Cap/518 alone. The
      frequencies of CD3+, CD3+CD4+CD8-, and CD3+CD4-CD8+ T cells in the combined
      immunization group were similar to that treated with CpG ODN alone, but
      significantly higher than mice that did not receive CpG ODN. PCV-2 load after
      challenge in the combined immunization group was significantly lower than that in
      the phosphate-buffered saline placebo group and approximately 7-fold lower in the
      group treated with CpG ODN alone. These results indicate that rAd/Cap/518
      combined with CpG ODN can enhance systemic and local mucosal immunity in mice,
      and represent a promising synergetic mucosal vaccine against PCV-2.

PMID- 24675839
TI  - Distribution, quantitative load and characterization of Salmonella associated
      with swine farms in upper-northern Thailand.
AB  - This study was conducted to analyze the prevalence and quantitative loads of
      Salmonella spp. on pig farms in Chiang Mai, Lamphun, Thailand to assess loading
      levels before slaughtering. The serotype diversity, antimicrobial-resistance
      pattern and pulse-field type of Salmonella spp. were also characterized to assess
      the dynamic propagation of the pathogen. The Salmonella-positive prevalence was
      246/805 (30.56%), and the quantitative loads varied from 1.48 ~ 4.04 Log10MPN/g,
      with a mean +/- standard deviation of 2.11 +/- 0.57. AMP/S/TE
      (ampicillin/streptomycin/tetracycline) was the highest frequency antimicrobial
      resistance pattern found in this study. In addition, Salmonella Rissen was the
      primary serotype in this region. PFGE results indicated the occurrence of
      infection by cross contamination among pig farms. Our study showed that pork is
      easily contaminated with this pathogen. Farm control programs must be based on
      strict biosecurity and hygienic measures, which could further reduce the
      contamination pressure at slaughterhouses or retail shops. 

PMID- 24675840
TI  - Mortality level and predictors in a rural Ethiopian population: community based
      longitudinal study.
AB  - BACKGROUND: Over the last fifty years the world has seen enormous decline in
      mortality rates. However, in low-income countries, where vital registration
      systems are absent, mortality statistics are not easily available. The recent
      economic growth of Ethiopia and the parallel large scale healthcare investments
      make investigating mortality figures worthwhile. METHODS: Longitudinal health and
      demographic surveillance data collected from September 11, 2009 to September 10,
      2012 were analysed. We computed incidence of mortality, overall and stratified by
      background variables. Poisson regression was used to test for a linear trend in
      the standardized mortality rates. Cox-regression analysis was used to identify
      predictors of mortality. Households located at <2300 meter and >= 2300 meter
      altitude were defined to be midland and highland, respectively. RESULTS: An open
      cohort, with a baseline population of 66,438 individuals, was followed for three
      years to generate 194,083 person-years of observation. The crude mortality rate
      was 4.04 (95% CI: 3.77, 4.34) per 1,000 person-years. During the follow-up
      period, incidence of mortality significantly declined among under five (P<0.001)
      and 5-14 years old (P<0.001), whereas it increased among 65 years and above
      (P<0.001). Adjusted for other covariates, mortality was higher in males (hazard
      ratio (HR) = 1.42, 95% CI: 1.22, 1.66), rural population (HR = 1.74, 95% CI:
      1.32, 2.31), highland (HR = 1.20, 95% CI: 1.03, 1.40) and among those widowed (HR
      = 2.25, 95% CI: 1.81, 2.80) and divorced (HR = 1.80, 95% CI: 1.30, 2.48).
      CONCLUSIONS: Overall mortality rate was low. The level and patterns of mortality
      indicate changes in the epidemiology of major causes of death. Certain population
      groups had significantly higher mortality rates and further research is warranted
      to identify causes of higher mortality in those groups.

PMID- 24675842
TI  - Adaptive expression of microRNA-125a in adipose tissue in response to obesity in
      mice and men.
AB  - MicroRNAs are emerging as new mediators in the regulation of adipose tissue
      biology and the development of obesity. An important role of microRNA-125a has
      been suggested in the pathogenesis of insulin resistance (IR). Here, we
      characterized the function of microRNA-125a in adipose tissue in a context of
      experimentally-induced IR and obesity in mice and in obese patients. We showed
      time dependent overexpression of the microRNA in adipose tissue of BALB/c and
      C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a
      expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and
      ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a
      expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set
      enrichment analysis (GSEA) identified significantly altered expression patterns
      of predicted microRNA-125a gene targets in transcriptomic datasets of adipose
      tissue from HFD-fed mice and obese patients. Among genes that contributed to
      global enrichment of altered expression of microRNA-125a targets, Thyrotroph
      embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and
      Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in
      adipose tissue in these groups. We showed that Tef expression is reduced in
      adipose tissue of obese patients following gastric bypass surgery. Our findings
      indicate that microRNA-125a expression in adipose tissue adapts to IR and may
      play a role in the development of obesity in mice and obese subjects through
      uncoupled regulation of the expression of microRNA-125a and its targets. 

PMID- 24675843
TI  - A rapid method for assaying thiaminase I activity in diverse biological samples.
AB  - Vitamin B1 (thiamine) deficiencies can lead to neurological disorders,
      reproductive failure and death in wild and domestic animal populations. In some
      cases, disease is brought about by the consumption of foods high in thiaminase I
      activity. Levels of thiaminase activity in these foods are highly variable and
      the factors leading to production of this enzyme are poorly understood. Here we
      describe improvements in a spectrophotometric thiaminase I activity assay that
      measures the disappearance of 4-nitrothiophenol, a favored nucleophile co
      substrate that replaces the thiazole portion of thiamine during the inactivation
      of thiamine by the enzyme. Scalable sample processing protocols and a 96-well
      microtiter plate format are presented that allow the rapid evaluation of
      multiple, replicated samples in the course of only a few hours. Observed levels
      of activity in bacterial culture supernatant, fish, ferns and molluscs using this
      colorimetric assay were similar to previously published reports that employed a
      radiometric method. Organisms devoid of thiaminase I, based upon previous work,
      showed no activity with this assay. In addition, activity was found in a variety
      of fishes and one fern species from which this enzyme had not previously been
      reported. Overall, we demonstrate the suitability of this technique for measuring
      thiaminase I activity within small amounts of tissue and environmental samples
      with replication levels that were heretofore prohibitive. The assay provides a
      considerable improvement in the ability to examine and understand the properties
      of an enzyme that has a substantial influence on organism and ecosystem health. 

PMID- 24675841
TI  - TBX3 regulates splicing in vivo: a novel molecular mechanism for Ulnar-mammary
      syndrome.
AB  - TBX3 is a member of the T-box family of transcription factors with critical roles
      in development, oncogenesis, cell fate, and tissue homeostasis. TBX3 mutations in
      humans cause complex congenital malformations and Ulnar-mammary syndrome.
      Previous investigations into TBX3 function focused on its activity as a
      transcriptional repressor. We used an unbiased proteomic approach to identify
      TBX3 interacting proteins in vivo and discovered that TBX3 interacts with
      multiple mRNA splicing factors and RNA metabolic proteins. We discovered that
      TBX3 regulates alternative splicing in vivo and can promote or inhibit splicing
      depending on context and transcript. TBX3 associates with alternatively spliced
      mRNAs and binds RNA directly. TBX3 binds RNAs containing TBX binding motifs, and
      these motifs are required for regulation of splicing. Our study reveals that TBX3
      mutations seen in humans with UMS disrupt its splicing regulatory function. The
      pleiotropic effects of TBX3 mutations in humans and mice likely result from
      disrupting at least two molecular functions of this protein: transcriptional
      regulation and pre-mRNA splicing. 

PMID- 24675844
TI  - Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore
      expanded mesoporous silica nanoparticles for PET.
AB  - Functional nanoparticles are highly interesting imaging agents for positron
      emission tomography (PET) due to the possibility of multiple incorporation of
      positron emitting radionuclides thus increasing the signal strength. Furthermore,
      long-term nanoparticle biodistribution tests with increased signal-to-noise ratio
      can be achieved with nanoparticles carrying long-lived isotopes. Mesoporous
      silica nanoparticles, MSNs, have recently attracted a lot of interest as both
      imaging agents and carriers for drugs in vitro and in vivo. Here we present
      results related to the synthesis of PET imageable MSNs carrying the long-lived
      (89)Zr isotope (half-life of 78.4 hours). Here, (89)Zr(4+) was immobilized
      through covalent attachment of the complexing agent p
      isothiocyanatobenzyldesferrioxamine (DFO-NCS) to large-pore MSNs. Due to the
      presence of the high DFO content on the MSNs, quantitative (89)Zr(4+) labeling
      was achieved within just a few minutes, and no subsequent purification step was
      needed in order to remove non-complexed (89)Zr(4+). The stability of the (89)Zr
      labeled MSNs against leaching of (89)Zr(4+) was verified for 24 hours. The high
      signal strength of the (89)Zr-DFO-MSNs was evidenced by successful PET imaging
      using a mouse model at particle loadings one order of magnitude lower than those
      previously applied in PET-MSN studies. The biodistribution followed the same
      trends as previously observed for MSNs of different sizes and surface
      functionalities. Taken together, our results suggest that (89)Zr-DFO-MSNs are
      promising PET imaging agents for long-term in vivo imaging. 

PMID- 24675845
TI  - Full-Genome Sequences of Influenza H3N2 Virus Strains Isolated from Finnish
      Patients during the 2012-2013 Epidemic Season.
AB  - Here, we sequenced 10 influenza A(H3N2) virus genomes isolated from Finnish
      patients diagnosed with flu-like illness during the 2012-2013 influenza season.
      The alignment showed a high number of amino acid substitutions (238 in total) in
      only 10 samples, proving that a high mutation rate exists in seasonal influenza A
      viruses. 

PMID- 24675846
TI  - Genome Sequence of a Presumptive Mannheimia haemolytica Strain with an A1/A6
      Cross-Reactive Serotype from a White-Tailed Deer (Odocoileus virginianus).
AB  - Mannheimia haemolytica is a Gram-negative bacterium and the principal etiological
      agent associated mostly with bovine respiratory disease complex. However, we
      report here the sequence of a strain with the novel A1/A6-cross-reactive
      serotype, strain PKL10, isolated from white-tailed deer. PKL10 was isolated from
      the spleen of farmed white-tailed deer showing clinical signs of pneumonia. The
      genome structure of PKL10 is dramatically different from that of previously
      sequenced isolates, which was demonstrated by genome alignments. In addition, the
      coding sequences in PKL10 share approximately 86% sequence identity with the
      coding sequences in other fully sequenced M. haemolytica strains. This suggests
      that PKL10 is a novel Mannheimia species. 

PMID- 24675847
TI  - Genome Sequence of a Complex HIV-1 Unique Recombinant Form Involving CRF01_AE,
      Subtype B, and Subtype B' Identified in Malaysia.
AB  - A complex HIV-1 unique recombinant form involving subtypes CRF01_AE, B, and B'
      was recently identified from an injecting drug user in Malaysia. A total of 13
      recombination breakpoints were mapped across the near-full-length genome of
      isolate 10MYPR226, indicating the increasingly diverse molecular epidemiology and
      frequent linkage among various high-risk groups. 

PMID- 24675848
TI  - Full-Genome Sequence of a Rare Human G3P[9] Rotavirus Strain.
AB  - This is a report of the complete genomic sequence of a rare rotavirus group A G3
      P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 strain designated RVA/Human
      wt/USA/12US1134/2012/G3P[9]. 

PMID- 24675849
TI  - Draft Genome Sequence of a New Homofermentative, Lactic Acid-Producing
      Enterococcus faecalis Isolate, CBRD01.
AB  - We report here the draft genome sequence of the novel homofermentative
      Enterococcus faecalis isolate CBRD01, which is capable of high lactic acid
      productivity and yields, with minimal nutritional requirements. The genome is 2.8
      Mbp, with 37% G+C, and contains genes for two lactate dehydrogenase (LDH) enzymes
      found in related organisms. 

PMID- 24675850
TI  - Draft Genome Sequence of an Invasive Multidrug-Resistant Strain, Pseudomonas
      aeruginosa BK1, Isolated from a Keratitis Patient.
AB  - Pseudomonas aeruginosa infections are difficult to treat due to the presence of a
      multitude of virulence factors and antibiotic resistance. Here, we report the
      draft genome sequence of P. aeruginosa BK1, an invasive and multidrug-resistant
      strain, isolated from a bacterial keratitis patient in southern India. 

PMID- 24675852
TI  - Draft Genome Sequence of Bacillus subtilis QH-1, a Chromium-Reducing Bacterial
      Strain Isolated in Qinghai Province, China.
AB  - Bacillus subtilis strain QH-1, a chromium-reducing bacterial strain, was isolated
      from a soil sample from a chromium-containing slag heap. The draft genome
      sequence of this bacterium is 4,034,036 bp in length, with a G+C content of
      43.71%, and it is predicted to contain 4,082 protein-coding genes. 

PMID- 24675851
TI  - Genome Sequence of Proteus mirabilis Clinical Isolate C05028.
AB  - Genomic DNA of Proteus mirabilis C05028 was sequenced by an Illumina HiSeq
      platform and was assembled to 39 scaffolds with a total length of 3.8 Mb. Next,
      open reading frames (ORFs) were identified and were annotated by the KEGG, COG,
      and NR databases. Finally, we found special virulence factors only existing in P.
      mirabilis C05028. 

PMID- 24675853
TI  - Draft Genome Sequence of Bifidobacterium animalis subsp. lactis Strain CECT 8145,
      Able To Improve Metabolic Syndrome In Vivo.
AB  - Bifidobacterium animalis subsp. lactis strain CECT 8145 is able to reduce body
      fat content and improve metabolic syndrome biomarkers. Here, we report the draft
      genome sequence of this strain, which may provide insights into its safety status
      and functional role. 

PMID- 24675854
TI  - Draft Genome Sequence of the Antarctic Polyextremophile Nesterenkonia sp. Strain
      AN1.
AB  - Nesterenkonia sp. strain AN1 was isolated from Antarctic soil and is a
      polyextremophile, being tolerant of low temperatures, high salt concentrations,
      and high alkalinity. Here we report the draft genome sequence of this strain. 

PMID- 24675855
TI  - Genome sequences of rhinovirus a isolates from wisconsin pediatric respiratory
      studies.
AB  - Full-length or nearly full-length RNA genome sequences for 98 rhinovirus (RV) A
      isolates (from the Enterovirus genus of the Picornaviridae family), representing
      43 different genotypes, were resolved as part of ongoing studies to define RV
      genetic diversity and its potential link to respiratory disease. 

PMID- 24675856
TI  - Draft Genome Sequence of Actinomadura madurae LIID-AJ290, Isolated from a Human
      Mycetoma Case.
AB  - Here we present the draft genome sequence of a member of the Thermomonosporaceae,
      Actinomadura madurae LIID-AJ290, isolated from a human case of mycetoma. The
      assembly contains 10,308,866 bp. This is to our knowledge the first reported
      genome of a human-pathogenic Actinomadura species. 

PMID- 24675857
TI  - Genome sequences of rhinovirus B isolates from wisconsin pediatric respiratory
      studies.
AB  - Nearly full-length RNA genome sequences for 39 rhinovirus B isolates (RV-B),
      representing 13 different genotypes, were resolved as part of ongoing studies at
      the University of Wisconsin that attempt to link rhinovirus (RV) diversity and
      respiratory disease in infants. 

PMID- 24675858
TI  - Genome sequences of rhinovirus C isolates from wisconsin pediatric respiratory
      studies.
AB  - Human rhinovirus (RV) isolates from the RV-C species are recently discovered
      infectious agents that are closely linked to asthma and wheezing etiologies in
      infants. Clinical study samples collected at the University of Wisconsin-Madison
      describe 41 nearly complete genome sequences representing 21 RV-C genotypes. 

PMID- 24675859
TI  - Draft Genome Sequence of Cytophaga fermentans JCM 21142T, a Facultative Anaerobe
      Isolated from Marine Mud.
AB  - Cytophaga fermentans strain JCM 21142(T) is a marine-dwelling facultative
      anaerobe. The draft genome sequence of this strain revealed its diverse
      chemoorganotrophic potential, which makes it capable of metabolizing various
      polysaccharide substrates. The genome data will facilitate further studies on its
      taxonomic reclassification, its metabolism, and the mechanisms pertaining to
      bacterial gliding. 

PMID- 24675860
TI  - Genome Sequence of Yersinia similis Y228T, a Member of the Yersinia
      pseudotuberculosis Complex.
AB  - We report here on the genome sequence of Yersinia similis 228(T) isolated in
      Germany. The genome has a size of 4.9 Mb and a G+C content of 47% and is
      predicted to contain 4,135 coding sequences. Annotation of the 60,687-bp
      extrachromosomal element predicted 67 coding sequences and a G+C content of
      47.8%. 

PMID- 24675861
TI  - Complete Genome Sequence for the Fusarium Head Blight Antagonist Bacillus
      amyloliquefaciens Strain TrigoCor 1448.
AB  - We present the complete genome sequence for Bacillus amyloliquefaciens TrigoCor
      1448 (ATCC 202152), a bacterial biological control agent for Fusarium head blight
      in wheat. We compare it to its closest relative, B. amyloliquefaciens strain
      AS43.3. 

PMID- 24675862
TI  - Genome Sequence of the Quorum-Quenching Rhodococcus erythropolis Strain R138.
AB  - Rhodococcus erythropolis strain R138 was isolated from the rhizosphere of Solanum
      tuberosum and selected for its capacity to degrade N-acyl-homoserine lactones,
      quorum-sensing signals used as communication molecules by the potato pathogens
      Pectobacterium and Dickeya. Here, we report the genome sequence of Rhodococcus
      erythropolis strain R138. 

PMID- 24675863
TI  - Genome Sequence of the Octopine-Type Agrobacterium tumefaciens Strain Ach5.
AB  - We have sequenced the complete genome of the plant pathogen Agrobacterium
      tumefaciens strain LBA4213, a derivative of the wild-type strain A. tumefaciens
      Ach5 and the ancestor of A. tumefaciens strain LBA4404 used in genetic
      engineering. The genome consists of a circular chromosome and a linear
      chromosome, as well as a megaplasmid and a tumor-inducing plasmid. 

PMID- 24675864
TI  - Identification of a Triple-Reassortant H1N1 Swine Influenza Virus in a Southern
      China Pig.
AB  - We report here the complete genome sequence of a triple-reassortant H1N1 swine
      influenza virus strain, A/swine/Guangxi/BB1/2013 (H1N1) (GXBB1), isolated from a
      swine in the Guangxi Province of southern China in 2013. We obtained the complete
      genome sequence of the GXBB1 virus. Sequence analysis demonstrated that this H1N1
      virus was a triple-reassortant swine influenza virus (SIV) whose genes originated
      from avian, human, and swine, respectively. Knowledge regarding the complete
      genome sequence of the GXBB1 virus will be useful for epidemiological
      surveillance. 

PMID- 24675865
TI  - Genome Sequence of a Hyperthermophilic Archaeon, Thermococcus nautili 30-1, That
      Produces Viral Vesicles.
AB  - Thermococcus nautili 30-1 (formerly Thermococcus nautilus), an anaerobic
      hyperthermophilic marine archaeon, was isolated in 1999 from a deep-sea
      hydrothermal vent during the Amistad campaign. Here, we present the complete
      sequence of T. nautili, which is able to produce membrane vesicles containing
      plasmid DNA. This property makes T. nautili a model organism to study horizontal
      gene transfer. 

PMID- 24675866
TI  - Draft Genome Sequences of Two Lactobacillus Strains, L. farraginis JCM 14108T and
      L. composti JCM 14202T, Isolated from Compost of Distilled Shochu Residue.
AB  - Here, we report the draft genome sequences of two type strains of Lactobacillus,
      Lactobacillus farraginis JCM 14108(T) and Lactobacillus composti JCM 14202(T),
      isolated from the compost of distilled shochu residue. Their genome information
      will be useful for studies of ecological and physiological functions of these
      Lactobacillus species. 

PMID- 24675867
TI  - Streptomyces alboflavus RPS and its novel and high algicidal activity against
      harmful algal bloom species Phaeocystis globosa.
AB  - Phaeocystis globosa blooms have frequently occurred along coastal waters and
      exerted serious impacts on ecological environments by releasing toxic hemolytic
      substances, forming nuisance foam, and causing oxygen depletion. An actinomycete
      strain RPS with high algicidal activity against P. globosa was isolated and
      identified as Streptomyces alboflavus, based on morphology, physiological and
      biochemical characteristics, and 16S rDNA sequence analysis. RPS lysed 95% of P.
      globosa within 48 h by releasing an extracellular active substance into the
      growth medium. The activity of RPS supernatant was sensitive to temperature at
      and above 50  degrees C and insensitive to pH from 3 to 11. The molecular weight
      of the active substance was between 100 Da and 1000 Da, and approximately 90% of
      it was extracted by ethyl acetate. It was presumed that the active component
      efficiently inhibited the movement of P. globosa, caused the flagella to fall off
      the algae, and finally lysed the algal cells. RPS showed a wide target range
      against harmful algae. S. alboflavus RPS with high algicidal activity and such
      novel features of temperature and pH sensitivity, low molecular weight, algicidal
      process, and target range possesses great potential in the biological control of
      P. globosa blooms.

PMID- 24675868
TI  - Rare variants detection with kernel machine learning based on likelihood ratio
      test.
AB  - This paper mainly utilizes likelihood-based tests to detect rare variants
      associated with a continuous phenotype under the framework of kernel machine
      learning. Both the likelihood ratio test (LRT) and the restricted likelihood
      ratio test (ReLRT) are investigated. The relationship between the kernel machine
      learning and the mixed effects model is discussed. By using the eigenvalue
      representation of LRT and ReLRT, their exact finite sample distributions are
      obtained in a simulation manner. Numerical studies are performed to evaluate the
      performance of the proposed approaches under the contexts of standard mixed
      effects model and kernel machine learning. The results have shown that the LRT
      and ReLRT can control the type I error correctly at the given alpha level. The
      LRT and ReLRT consistently outperform the SKAT, regardless of the sample size and
      the proportion of the negative causal rare variants, and suffer from fewer power
      reductions compared to the SKAT when both positive and negative effects of rare
      variants are present. The LRT and ReLRT performed under the context of kernel
      machine learning have slightly higher powers than those performed under the
      context of standard mixed effects model. We use the Genetic Analysis Workshop 17
      exome sequencing SNP data as an illustrative example. Some interesting results
      are observed from the analysis. Finally, we give the discussion. 

PMID- 24675869
TI  - The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A
      Functional Magnetic Resonance Imaging Study.
AB  - Behavioral evidence indicates that working memory (WM) in schizophrenia is
      already impaired at the encoding stage. However, the neurophysiological basis of
      this primary deficit remains poorly understood. Using event-related fMRI, we
      assessed differences in brain activation and functional connectivity during the
      encoding, maintenance and retrieval stages of a visual WM task with 3 levels of
      memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched
      controls. The amount of information patients could store in WM was reduced at all
      memory load levels. During encoding, activation in left ventrolateral prefrontal
      cortex (VLPFC) and extrastriate visual cortex, which in controls positively
      correlated with the amount of stored information, was reduced in patients.
      Additionally, patients showed disturbed functional connectivity between
      prefrontal and visual areas. During retrieval, right inferior VLPFC
      hyperactivation was correlated with hypoactivation of left VLPFC in patients
      during encoding. Visual WM encoding is disturbed by a failure to adequately
      engage a visual-prefrontal network critical for the transfer of perceptual
      information into WM. Prefrontal hyperactivation appears to be a secondary
      consequence of this primary deficit. Isolating the component processes of WM can
      lead to more specific neurophysiological markers for translational efforts
      seeking to improve the treatment of cognitive dysfunction in schizophrenia. 

PMID- 24675870
TI  - White Matter Tracts Connected to the Medial Temporal Lobe Support the Development
      of Mnemonic Control.
AB  - One of the most important factors driving the development of memory during
      childhood is mnemonic control, or the capacity to initiate and maintain the
      processes that guide encoding and retrieval operations. The ability to
      selectively attend to and encode relevant stimuli is a particularly useful form
      of mnemonic control, and is one that undergoes marked improvement over childhood.
      We hypothesized that structural integrity of white matter tracts, in particular
      those connecting medial temporal lobe memory regions to other cortical areas,
      and/or those connecting frontal and parietal control regions, should contribute
      to successful mnemonic control. To test this hypothesis, we examined the
      relationship between structural integrity of selected white matter tracts and an
      experimental measure of mnemonic control, involving enhancement of memory by
      attention at encoding, in 116 children aged 7-11 and 25 young adults. We observed
      a positive relationship between integrity of uncinate fasciculus and mnemonic
      enhancement across age groups. In adults, but not in children, we also observed
      an association between mnemonic enhancement and integrity of ventral cingulum
      bundle and ventral fornix/fimbria. Integrity of fronto-parietal tracts, including
      dorsal cingulum and superior longitudinal fasciculus, was unrelated to mnemonic
      enhancement. 

PMID- 24675872
TI  - Unveiling the effects of post-deposition treatment with different alkaline
      elements on the electronic properties of CIGS thin film solar cells.
AB  - Thin film solar cells with a Cu(In,Ga)Se2 (CIGS) absorber layer achieved
      efficiencies above 20%. In order to achieve such high performance the absorber
      layer of the device has to be doped with alkaline material. One possibility to
      incorporate alkaline material is a post deposition treatment (PDT), where a thin
      layer of NaF and/or KF is deposited onto the completely grown CIGS layer. In this
      paper we discuss the effects of PDT with different alkaline elements (Na and K)
      on the electronic properties of CIGS solar cells. We demonstrate that whereas Na
      is more effective in increasing the hole concentration in CIGS, K significantly
      improves the pn-junction quality. The beneficial role of K in improving the PV
      performance is attributed to reduced recombination at the CdS/CIGS interface, as
      revealed by temperature dependent J-V measurements, due to a stronger
      electronically inverted CIGS surface region. Computer simulations with the
      software SCAPS are used to verify this model. Furthermore, we show that PDT with
      either KF or NaF has also a distinct influence on other electronic properties of
      the device such as the position of the N1 signal in admittance spectroscopy and
      the roll-over of the J-V curve at low temperature. In view of the presented
      results we conclude that a model based on a secondary diode at the CIGS/Mo
      interface can best explain these features. 

PMID- 24675871
TI  - Increased expression of p62/SQSTM1 in prion diseases and its association with
      pathogenic prion protein.
AB  - Prion diseases are neurodegenerative disorders characterized by the aggregation
      of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the
      mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic
      protein known to mediate both the formation and degradation of aggregates of
      abnormal proteins. The levels of p62 protein increased in prion-infected brains
      and persistently infected cell cultures. Upon proteasome inhibition, p62 co
      localized with PrP(Sc), forming a large aggregate in the perinuclear region,
      hereafter referred to as PrP(Sc)-aggresome. These aggregates were surrounded with
      autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover,
      transient expression of the phosphomimic form of p62, which has enhanced
      ubiquitin-binding activity, reduced the amount of PrP(Sc) in prion-infected
      cells, indicating that the activation of p62 could accelerate the clearance of
      PrP(Sc). Our findings would thus suggest that p62 could be a target for the
      therapeutic control of prion diseases. 

PMID- 24675873
TI  - Microfluidic source-sink model reveals effects of biophysically distinct CXCL12
      isoforms in breast cancer chemotaxis.
AB  - Chemokines critically regulate chemotaxis in normal and pathologic states, but
      there is limited understanding of how multicellular interactions generate
      gradients needed for cell migration. Previous studies of chemotaxis of CXCR4+
      cells toward chemokine CXCL12 suggest the requirement of cells expressing
      scavenger receptor CXCR7 in a source-sink system. We leveraged an established
      microfluidic device to discover that chemotaxis of CXCR4 cells toward distinct
      isoforms of CXCL12 required CXCR7 scavenging only under conditions with higher
      than optimal levels of CXCL12. Chemotaxis toward CXCL12-beta and -gamma isoforms,
      which have greater binding to extracellular molecules and have been largely
      overlooked, was less dependent on CXCR7 than the more commonly studied CXCL12
      alpha. Chemotaxis of CXCR4+ cells toward even low levels of CXCL12-gamma and
      CXCL12-beta still occurred during treatment with a FDA-approved inhibitor of
      CXCR4. We also detected CXCL12-gamma only in breast cancers from patients with
      advanced disease. Physiological gradient formation within the device facilitated
      interrogation of key differences in chemotaxis among CXCL12 isoforms and suggests
      CXCL12-gamma as a biomarker for metastatic cancer. 

PMID- 24675874
TI  - Structural and functional characterization of a complex between the acidic
      transactivation domain of EBNA2 and the Tfb1/p62 subunit of TFIIH.
AB  - Infection with the Epstein-Barr virus (EBV) can lead to a number of human
      diseases including Hodgkin's and Burkitt's lymphomas. The development of these
      EBV-linked diseases is associated with the presence of nine viral latent
      proteins, including the nuclear antigen 2 (EBNA2). The EBNA2 protein plays a
      crucial role in EBV infection through its ability to activate transcription of
      both host and viral genes. As part of this function, EBNA2 associates with
      several host transcriptional regulatory proteins, including the Tfb1/p62
      (yeast/human) subunit of the general transcription factor IIH (TFIIH) and the
      histone acetyltransferase CBP(CREB-binding protein)/p300, through interactions
      with its C-terminal transactivation domain (TAD). In this manuscript, we examine
      the interaction of the acidic TAD of EBNA2 (residues 431-487) with the Tfb1/p62
      subunit of TFIIH and CBP/p300 using nuclear magnetic resonance (NMR)
      spectroscopy, isothermal titration calorimeter (ITC) and transactivation studies
      in yeast. NMR studies show that the TAD of EBNA2 binds to the pleckstrin homology
      (PH) domain of Tfb1 (Tfb1PH) and that residues 448-471 (EBNA2448-471) are
      necessary and sufficient for this interaction. NMR structural characterization of
      a Tfb1PH-EBNA2448-471 complex demonstrates that the intrinsically disordered TAD
      of EBNA2 forms a 9-residue alpha-helix in complex with Tfb1PH. Within this helix,
      three hydrophobic amino acids (Trp458, Ile461 and Phe462) make a series of
      important interactions with Tfb1PH and their importance is validated in ITC and
      transactivation studies using mutants of EBNA2. In addition, NMR studies indicate
      that the same region of EBNA2 is also required for binding to the KIX domain of
      CBP/p300. This study provides an atomic level description of interactions
      involving the TAD of EBNA2 with target host proteins. In addition, comparison of
      the Tfb1PH-EBNA2448-471 complex with structures of the TAD of p53 and VP16 bound
      to Tfb1PH highlights the versatility of intrinsically disordered acidic TADs in
      recognizing common target host proteins.

PMID- 24675876
TI  - Indentation-formed nanocontacts: an atomic-scale perspective.
AB  - One-to-one comparisons between indentation experiments and atomistic modelling
      have until recently been hampered by the discrepancy in length scales of the two
      approaches. Here, we review progress in atomic-scale nanoindentation experiments
      employing scanning probe techniques to achieve depth-sensing indentation and
      field ion microscopy to permit detailed indenter characterization. This
      perspective addresses both mechanical (dislocation nucleation, defect structures,
      adhesion, indenter effects) and electronic (interface, disorder, and vacancy
      scattering) properties of indentation-formed contacts. 

PMID- 24675875
TI  - Evaluation and structure-activity relationship analysis of a new series of
      arylnaphthalene lignans as potential anti-tumor agents.
AB  - Arylnaphthalene lignan lactones have attracted considerable interest because of
      their anti-tumor and anti-hyperlipidimic activities. However, to our knowledge,
      few studies have explored the effects of these compounds on human leukemia cell
      lines. In this study, five arylnaphthalene lignans including 6'-hydroxy
      justicidin A (HJA), 6'-hydroxy justicidin B (HJB), justicidin B (JB),
      chinensinaphthol methyl ether (CME) and Taiwanin E methyl ether (TEME) were
      isolated from Justicia procumbens and their effects on the proliferation and
      apoptosis of the human leukemia K562 cell line were investigated then used to
      assess structure-activity relationships. To achieve these aims, cytotoxicity was
      assayed using the MTT assay, while intracellular SOD activity was detected using
      the SOD Activity Assay kit. Apoptosis was measured by both the using a cycle TEST
      PLUS DNA reagent kit as well as the FITC Annexin V apoptosis detection kit in
      combination with flow cytometry. Activation of caspase-mediated apoptosis was
      evaluated using a FITC active Caspase-3 apoptosis kit and flow cytometry. The
      results indicated that HJB, HJA and JB significantly inhibited the growth of K562
      cells by decreasing both proliferation and SOD activity and inducing apoptosis.
      The sequence of anti-proliferative activity induced by the five tested
      arylnaphthalenes by decreasing strength was HJB > HJA > JB > CME > TEME. HJB, HJA
      and JB also decreased SOD activity and induced apoptosis in a dose-dependent
      manner. Activation of caspase-3 further indicated that HJB, HJA and JB induced
      caspase-dependent intrinsic and/or extrinsic apoptosis pathways. Together, these
      assays suggest that arylnaphthalene lignans derived from Justicia procumbens
      induce apoptosis to varying degrees, through a caspase-dependent pathway in human
      leukemia K562 cells. Furthermore, analysis of structure-activity relationships
      suggest that hydroxyl substitution at C-1 and C-6' significantly increased the
      antiproliferative activity of arylnaphthalene lignans while a methoxyl at C-1
      significantly decreased the effect. 

PMID- 24675877
TI  - Complexity generation by chemical synthesis: a five-step synthesis of (-)
      chaetominine from L-tryptophan and its biosynthetic implications.
AB  - We demonstrated, for the first time, that on the basis of chemistry principles,
      the hexacyclic peptidyl alkaloid (-)-chaetominine (1) can be synthesized in a
      straightforward manner from L-Trp. The approach features the efficient generation
      of molecular complexity via a tandem C3/C14 syn-selective epoxidation (dr = 3:2)
      annulative ring-opening reaction and a regioselective epimerization at C14. The
      successful production of (-)-chaetominine (1) from L-Trp could be helpful for
      revealing how the configuration of L-tryptophan becomes inverted in the
      biosynthetic pathway of (-)-chaetominine (1).

PMID- 24675878
TI  - Identification of interphase functions for the NIMA kinase involving microtubules
      and the ESCRT pathway.
AB  - The Never in Mitosis A (NIMA) kinase (the founding member of the Nek family of
      kinases) has been considered a mitotic specific kinase with nuclear restricted
      roles in the model fungus Aspergillus nidulans. By extending to A. nidulans the
      results of a synthetic lethal screen performed in Saccharomyces cerevisiae using
      the NIMA ortholog KIN3, we identified a conserved genetic interaction between
      nimA and genes encoding proteins of the Endosomal Sorting Complex Required for
      Transport (ESCRT) pathway. Absence of ESCRT pathway functions in combination with
      partial NIMA function causes enhanced cell growth defects, including an inability
      to maintain a single polarized dominant cell tip. These genetic insights suggest
      NIMA potentially has interphase functions in addition to its established mitotic
      functions at nuclei. We therefore generated endogenously GFP-tagged NIMA (NIMA
      GFP) which was fully functional to follow its interphase locations using live
      cell spinning disc 4D confocal microscopy. During interphase some NIMA-GFP
      locates to the tips of rapidly growing cells and, when expressed ectopically,
      also locates to the tips of cytoplasmic microtubules, suggestive of non-nuclear
      interphase functions. In support of this, perturbation of NIMA function either by
      ectopic overexpression or through partial inactivation results in marked cell tip
      growth defects with excess NIMA-GFP promoting multiple growing cell tips. Ectopic
      NIMA-GFP was found to locate to the plus ends of microtubules in an EB1 dependent
      manner, while impairing NIMA function altered the dynamic localization of EB1 and
      the cytoplasmic microtubule network. Together, our genetic and cell biological
      analyses reveal novel non-nuclear interphase functions for NIMA involving
      microtubules and the ESCRT pathway for normal polarized fungal cell tip growth.
      These insights extend the roles of NIMA both spatially and temporally and
      indicate that this conserved protein kinase could help integrate cell cycle
      progression with polarized cell growth. 

PMID- 24675879
TI  - Cathelicidins from the bullfrog Rana catesbeiana provides novel template for
      peptide antibiotic design.
AB  - Cathelicidins, a class of gene-encoded effector molecules of vertebrate innate
      immunity, provide a first line of defense against microbial invasions. Although
      cathelicidins from mammals, birds, reptiles and fishes have been extensively
      studied, little is known about cathelicidins from amphibians. Here we report the
      identification and characterization of two cathelicidins (cathelicidin-RC1 and
      cathelicidin-RC2) from the bullfrog Rana catesbeiana. The cDNA sequences (677 and
      700 bp, respectively) encoding the two peptides were successfully cloned from the
      constructed lung cDNA library of R. catesbeiana. And the deduced mature peptides
      are composed of 28 and 33 residues, respectively. Structural analysis indicated
      that cathelicidin-RC1 mainly assumes an amphipathic alpha-helical conformation,
      while cathelicidin-RC2 could not form stable amphipathic structure. Antimicrobial
      and bacterial killing kinetic analysis indicated that the synthetic cathelicidin
      RC1 possesses potent, broad-spectrum and rapid antimicrobial potency, while
      cathelicidin-RC2 exhibited very weak antimicrobial activity. Besides, the
      antimicrobial activity of cathelicidin-RC1 is salt-independent and highly stable.
      Scanning electron microscopy (SEM) analysis indicated that cathelicidin-RC1 kills
      microorganisms through the disruption of microbial membrane. Moreover,
      cathelicidin-RC1 exhibited low cytotoxic activity against mammalian normal or
      tumor cell lines, and low hemolytic activity against human erythrocytes. The
      potent, broad-spectrum and rapid antimicrobial activity combined with the salt
      independence, high stability, low cytotoxic and hemolytic activities make
      cathelicidin-RC1 an ideal template for the development of novel peptide
      antibiotics. 

PMID- 24675880
TI  - Extracellular proteolysis of apolipoprotein E (apoE) by secreted serine neuronal
      protease.
AB  - Under normal conditions, brain apolipoprotein E (apoE) is secreted and lipidated
      by astrocytes, then taken up by neurons via receptor mediated endocytosis. Free
      apoE is either degraded in intraneuronal lysosomal compartments or released. Here
      we identified a novel way by which apoE undergoes proteolysis in the
      extracellular space via a secreted neuronal protease. We show that apoE is
      cleaved in neuronal conditioned media by a secreted serine protease. This apoE
      cleavage was inhibited by PMSF and alpha1-antichymotrypsin, but not neuroserpin-1
      or inhibitors of thrombin and cathepsin G, supporting its identity as a
      chymotrypsin like protease. In addition, apoE incubation with purified
      chymotrypsin produced a similar pattern of apoE fragments. Analysis of apoE
      fragments by mass spectrometry showed cleavages occurring at the C-terminal side
      of apoE tryptophan residues, further supporting our identification of cleavage by
      chymotrypsin like protease. Hippocampal neurons were more efficient in mediating
      this apoE cleavage than cortical neurons. Proteolysis of apoE4 generated higher
      levels of low molecular weight fragments compared to apoE3. Primary glial
      cultures released an inhibitor of this proteolytic activity. Together, these
      studies reveal novel mechanism by which apoE can be regulated and therefore could
      be useful in designing apoE directed AD therapeutic approaches.

PMID- 24675881
TI  - Role of CDK5/cyclin complexes in ischemia-induced death and survival of renal
      tubular cells.
AB  - Ischemia reperfusion processes induce damage in renal tubules and compromise the
      viability of kidney transplants. Understanding the molecular events responsible
      for tubule damage and recovery would help to develop new strategies for organ
      preservation. CDK5 has been traditionally considered a neuronal kinase with dual
      roles in cell death and survival. Here, we demonstrate that CDK5 and their
      regulators p35/p25 and cyclin I are also expressed in renal tubular cells. We
      show that treatment with CDK inhibitors promotes the formation of pro-survival
      CDK5/cyclin I complexes and enhances cell survival upon an ischemia reperfusion
      pro-apoptotic insult. These findings support the benefit of treating with CDK
      inhibitors for renal preservation, assisting renal tubule protection. 

PMID- 24675882
TI  - Establishment of a replication fork barrier following induction of DNA binding in
      mammalian cells.
AB  - Understanding the mechanisms that lead to replication fork blocks (RFB) and the
      means to bypass them is important given the threat that they represent for genome
      stability if inappropriately handled. Here, to study this issue in mammals, we
      use integrated arrays of the LacO and/or TetO as a tractable system to follow in
      time a process in an individual cell and at a single locus. Importantly, we show
      that induction of the binding by LacI and TetR proteins, and not the presence of
      the repeats, is key to form the RFB. We find that the binding of the proteins to
      the arrays during replication causes a prolonged persistence of replication foci
      at the site. This, in turn, induces a local DNA damage repair (DDR) response,
      with the recruitment of proteins involved in double-strand break (DSB) repair
      such as TOPBP1 and 53BP1, and the phosphorylation of H2AX. Furthermore, the
      appearance of micronuclei and DNA bridges after mitosis is consistent with an
      incomplete replication. We discuss how the many DNA binding proteins encountered
      during replication can be dealt with and the consequences of incomplete
      replication. Future studies exploiting this type of system should help analyze
      how an RFB, along with bypass mechanisms, are controlled in order to maintain
      genome integrity. 

PMID- 24675883
TI  - alpha-endosulfine (ENSA) regulates exit from prophase I arrest in mouse oocytes.
AB  - Mammalian oocytes in ovarian follicles are arrested in meiosis at prophase I.
      This arrest is maintained until ovulation, upon which the oocyte exits from this
      arrest, progresses through meiosis I and to metaphase of meiosis II. The
      progression from prophase I to metaphase II, known as meiotic maturation, is
      mediated by signals that coordinate these transitions in the life of the oocyte.
      ENSA (alpha-endosulfine) and ARPP19 (cAMP-regulated phosphoprotein-19) have
      emerged as regulators of M-phase, with function in inhibition of protein
      phosphatase 2A (PP2A) activity. Inhibition of PP2A maintains the phosphorylated
      state of CDK1 substrates, thus allowing progression into and/or maintenance of an
      M-phase state. We show here ENSA in mouse oocytes plays a key role in the
      progression from prophase I arrest into M-phase of meiosis I. The majority of
      ENSA-deficient oocytes fail to exit from prophase I arrest. This function of ENSA
      in oocytes is dependent on PP2A, and specifically on the regulatory subunit
      PPP2R2D (also known as B55delta). Treatment of ENSA-deficient oocytes with
      Okadaic acid to inhibit PP2A rescues the defect in meiotic progression, with
      Okadaic acid-treated, ENSA-deficient oocytes being able to exit from prophase I
      arrest. Similarly, oocytes deficient in both ENSA and PPP2R2D are able to exit
      from prophase I arrest to an extent similar to wild-type oocytes. These data are
      evidence of a role for ENSA in regulating meiotic maturation in mammalian
      oocytes, and also have potential relevance to human oocyte biology, as mouse and
      human have genes encoding both Arpp19 and Ensa. 

PMID- 24675885
TI  - Tissue-specific inactivation of HAT cofactor TRRAP reveals its essential role in
      B cells.
AB  - The transformation/transcription domain-associated protein (TRRAP) is a common
      component of many histone acetyltransferase (HAT) complexes. Targeted-deletion of
      the Trrap gene led to early embryonic lethality and revealed a critical function
      of TRRAP in cell proliferation. Here, we investigate the function of TRRAP in
      murine B cells. To this end, we ablated Trrap gene in a B cell-restricted manner
      and studied its impact on B-cell development and proliferation, a pre-requisite
      for class switch recombination (CSR), the process that allows IgM-expressing B
      lymphocytes to switch to the expression of IgG, IgE, or IgA isotypes. We show
      that TRRAP deficiency impairs B-cell development but does not directly affect
      CSR. Instead, cells induced to proliferate undergo apoptosis. Our findings
      demonstrate a central and general role of TRRAP in cell proliferation. 

PMID- 24675884
TI  - ATM-dependent E2F1 accumulation in the nucleolus is an indicator of ribosomal
      stress in early response to DNA damage.
AB  - The nucleolus plays a major role in ribosome biogenesis. Most genotoxic agents
      disrupt nucleolar structure and function, which results in the
      stabilization/activation of p53, inducing cell cycle arrest or apoptosis.
      Likewise, transcription factor E2F1 as a DNA damage responsive protein also plays
      roles in cell cycle arrest, DNA repair, or apoptosis in response to DNA damage
      through transcriptional response and protein-protein interaction. Furthermore,
      E2F1 is known to be involved in regulating rRNA transcription. However, how E2F1
      displays in coordinating DNA damage and nucleolar stress is unclear. In this
      study, we demonstrate that ATM-dependent E2F1 accumulation in the nucleolus is a
      characteristic feature of nucleolar stress in early response to DNA damage. We
      found that at the early stage of DNA damage, E2F1 accumulation in the nucleolus
      was an ATM-dependent and a common event in p53-suficient and -deficient cells.
      Increased nucleolar E2F1 was sequestered by the nucleolar protein p14ARF, which
      repressed E2F1-dependent rRNA transcription initiation, and was coupled with S
      phase. Our data indicate that early accumulation of E2F1 in the nucleolus is an
      indicator for nucleolar stress and a component of ATM pathway, which presumably
      buffers elevation of E2F1 in the nucleoplasm and coordinates the diversifying
      mechanisms of E2F1 acts in cell cycle progression and apoptosis in early response
      to DNA damage. 

PMID- 24675886
TI  - Distinct spatiotemporal expression of ISM1 during mouse and chick development.
AB  - Isthmin 1 (ISM1) constitutes the founder of a new family of secreted proteins
      characterized by the presence of 2 functional domains: thrombospondin type 1
      repeat (TSR1) and adhesion-associated domain in MUC4 and other proteins (AMOP).
      ISM1 was identified in the frog embryo as a member of the FGF8 synexpression
      group due to its expression in the brain midbrain-hindbrain boundary (MHB) or
      isthmus. In zebrafish, ISM1 was described as a WNT- and NODAL-regulated gene. The
      function of ISM1 remains largely elusive. So far, ISM1 has been described as an
      angiogenesis inhibitor that has a dual function in endothelial cell survival and
      cell death. For a better understanding of ISM1 function, we examined its
      spatiotemporal distribution in mouse and chick using RT-PCR, ISH, and IHC
      analyses. In the mouse, ISM1 transcripts are found in tissues such as the
      anterior mesendoderm, paraxial and lateral plate mesoderm, MHB and trunk neural
      tube, as well as in the somites and dermomyotome. In the newborn and adult, ISM1
      is prominently expressed in the lung and brain. In addition to its putative role
      during embryonic and postnatal development, ISM1 may also be important for organ
      homeostasis in the adult. In the chick embryo, ISM1 transcripts are strongly
      detected in the ear, eye, and spinal cord primordia. Remarkable differences in
      ISM1 spatiotemporal expression were found during mouse and chick development,
      despite the high homology of ISM1 orthologs in these species. 

PMID- 24675887
TI  - Promyelocytic leukemia bodies tether to early endosomes during mitosis.
AB  - During mitosis the nuclear envelope breaks down, leading to potential
      interactions between cytoplasmic and nuclear components. PML bodies are nuclear
      structures with tumor suppressor and antiviral functions. Early endosomes, on the
      other hand, are cytoplasmic vesicles involved in transport and growth factor
      signaling. Here we demonstrate that PML bodies form stable interactions with
      early endosomes immediately following entry into mitosis. The 2 compartments
      remain stably associated throughout mitosis and dissociate in the cytoplasm of
      newly divided daughter cells. We also show that a minor subset of PML bodies
      becomes anchored to the mitotic spindle poles during cell division. The study
      demonstrates a stable mitosis-specific interaction between a cytoplasmic and a
      nuclear compartment. 

PMID- 24675888
TI  - Phosphorylation-mediated stabilization of Bora in mitosis coordinates Plx1/Plk1
      and Cdk1 oscillations.
AB  - Cdk1 and Plk1/Plx1 activation leads to their inactivation through negative
      feedback loops. Cdk1 deactivates itself by activating the APC/C, consequently
      generating embryonic cell cycle oscillations. APC/C inhibition by the mitotic
      checkpoint in somatic cells and the cytostatic factor (CSF) in oocytes sustain
      the mitotic state. Plk1/Plx1 targets its co-activator Bora for degradation, but
      it remains unclear how embryonic oscillations in Plx1 activity are generated, and
      how Plk1/Plx1 activity is sustained during mitosis. We show that Plx1-mediated
      degradation of Bora in interphase generates oscillations in Plx1 activity and is
      essential for development. In CSF extracts, phosphorylation of Bora on the Cdk
      consensus site T52 blocks Bora degradation. Upon fertilization, Calcineurin
      dephosphorylates T52, triggering Plx1 oscillations. Similarly, we find that GFP
      Bora is degraded when Plk1 activity spreads to somatic cell cytoplasm before
      mitosis. Interestingly, GFP-Bora degradation stops upon mitotic entry when Cdk1
      activity is high. We hypothesize that Cdk1 controls Bora through an incoherent
      feedforward loop synchronizing the activities of mitotic kinases. 

PMID- 24675889
TI  - Lineage-specific function of Engrailed-2 in the progression of chronic
      myelogenous leukemia to T-cell blast crisis.
AB  - In hematopoietic malignancies, oncogenic alterations interfere with cellular
      differentiation and lead to tumoral development. Identification of the proteins
      regulating differentiation is essential to understand how they are altered in
      malignancies. Chronic myelogenous leukemia (CML) is a biphasic disease initiated
      by an alteration taking place in hematopoietic stem cells. CML progresses to a
      blast crisis (BC) due to a secondary differentiation block in any of the
      hematopoietic lineages. However, the molecular mechanisms of CML evolution to T
      cell BC remain unclear. Here, we have profiled the changes in DNA methylation
      patterns in human samples from BC-CML, in order to identify genes whose
      expression is epigenetically silenced during progression to T-cell lineage
      specific BC. We have found that the CpG-island of the ENGRAILED-2 (EN2) gene
      becomes methylated in this progression. Afterwards, we demonstrate that En2 is
      expressed during T-cell development in mice and humans. Finally, we further show
      that genetic deletion of En2 in a CML transgenic mouse model induces a T-cell
      lineage BC that recapitulates human disease. These results identify En2 as a new
      regulator of T-cell differentiation whose disruption induces a malignant T-cell
      fate in CML progression, and validate the strategy used to identify new
      developmental regulators of hematopoiesis. 

PMID- 24675890
TI  - Doxorubicin enhances Snail/LSD1-mediated PTEN suppression in a PARP1-dependent
      manner.
AB  - The transcription factor Snail not only functions as a master regulator of
      epithelial-mesenchymal transition (EMT), but also mediates cell proliferation and
      survival. While previous studies have showed that Snail protects tumor cells from
      apoptosis through transcriptional repression of PTEN, the specific mechanism
      remains unclear. In this study, we demonstrated that Snail cooperates with LSD1
      to repress PTEN in a PARP1-dependent manner. Upon doxorubicin treatment, Snail
      becomes tightly associated with PARP1 through its pADPr-binding motif and is
      subject to poly(ADP-ribosyl)ation. This modification can enhance Snail-LSD1
      interaction and promote the recruitment of LSD1 to PTEN promoter, where LSD1
      removes methylation on histone H3 lysine 4 for transcription repression.
      Furthermore, treatment of tumor cells with PARP1 inhibitor AZD2281 can compromise
      doxorubicin-induced PTEN suppression and enhance the inhibitory effect of
      doxorubicin. Together, we proposed a tentative drug-resistant mechanism through
      which tumor cells defend themselves against DNA damage-induced apoptosis. PARP1
      inhibitors in combination with DNA damaging reagents might represent a promising
      treatment strategy targeting tumors with over-activated Snail and LSD1. 

PMID- 24675892
TI  - BAG3 mRNA is present in synaptosomal polysomes of rat brain.

PMID- 24675891
TI  - Knockdown of astrocyte elevated gene-1 (AEG-1) in cervical cancer cells decreases
      their invasiveness, epithelial to mesenchymal transition, and chemoresistance.
AB  - During cancer development, epithelial-mesenchymal transition (EMT) facilitates
      tumor dissemination and metastatic spread, which is characterized by morphologic
      changes from epithelial cells to fibroblast-like cells, disassembly of
      intercellular junction, and increased cell motility. Overexpression of astrocyte
      elevated gene-1(AEG-1) in various cancer cell lines and cancers has been found to
      be associated with aggressive tumor behavior. We found that AEG-1 expression was
      elevated in low differentiation cervical cancer specimens from patients. However,
      little is known about the AEG-1's precise role in invasion and metastasis. Here
      we demonstrate that downregulation of AEG-1 by RNAi significantly decreased the
      invasion and migration of cervical cancer cells, suggesting that AEG-1
      overexpression may enhance cancer cell motility by inducing EMT. Downregulation
      of AEG-1 also led to reduced expression of mesenchymal marker vimentin and the
      transcription factor Snail but upregulation of epithelial marker E-cadherin in
      HeLa cells. In addition, knockdown of AEG-1 decreased colony forming units and
      increased sensitivity to cancer drugs in vitro. Taken together, our results
      suggest that knockdown of AEG-1 could decrease EMT and chemoresistance in
      cervical cancer cells and attenuate their aggressive behavior. 

PMID- 24675893
TI  - MKK7 and ARF: new players in the DNA damage response scenery.
AB  - Sensing, integrating, and processing of stressogenic signals must be followed by
      accurate differential response(s) for a cell to survive and avoid malignant
      transformation. The DNA damage response (DDR) pathway is vital in this process,
      as it deals with genotoxic/oncogenic insults, having p53 as a nodal effector that
      performs most of the above tasks. Accumulating data reveal that other pathways
      are also involved in the same or similar processes, conveying also to p53.
      Emerging questions are if, how, and when these additional pathways communicate
      with the DDR axis. Two such stress response pathways, involving the MKK7 stress
      activated protein kinase (SAPK) and ARF, have been shown to be interlocked with
      the ATM/ATR-regulated DDR axis in a highly ordered manner. This creates a new
      landscape in the DDR orchestrated response to genotoxic/oncogenic insults that is
      currently discussed. 

PMID- 24675894
TI  - Divide and differentiate: CDK/Cyclins and the art of development.
AB  - The elegant choreography of metazoan development demands exquisite regulation of
      cell-division timing, orientation, and asymmetry. In this review, we discuss
      studies in Drosophila and C. elegans that reveal how the cell cycle machinery,
      comprised of cyclin-dependent kinase (CDK) and cyclins functions as a master
      regulator of development. We provide examples of how CDK/cyclins: (1) regulate
      the asymmetric localization and timely destruction of cell fate determinants; (2)
      couple signaling to the control of cell division orientation; and (3) maintain
      mitotic zones for stem cell proliferation. These studies illustrate how the core
      cell cycle machinery should be viewed not merely as an engine that drives the
      cell cycle forward, but rather as a dynamic regulator that integrates the cell
      division cycle with cellular differentiation, ensuring the coherent and faithful
      execution of developmental programs. 

PMID- 24675895
TI  - Helminth-associated systemic immune activation and HIV co-receptor expression:
      response to albendazole/praziquantel treatment.
AB  - BACKGROUND: It has been hypothesized that helminth infections increase HIV
      susceptibility by enhancing systemic immune activation and hence contribute to
      elevated HIV-1 transmission in sub-Saharan Africa. OBJECTIVE: To study systemic
      immune activation and HIV-1 co-receptor expression in relation to different
      helminth infections and in response to helminth treatment. METHODS: HIV-negative
      adults with (n = 189) or without (n = 57) different helminth infections, as
      diagnosed by Kato-Katz, were enrolled in Mbeya, Tanzania. Blinded to helminth
      infection status, T cell differentiation (CD45RO, CD27), activation (HLA-DR,
      CD38) and CCR5 expression was determined at baseline and 3 months after
      Albendazole/Praziquantel treatment. Plasma cytokine levels were compared using a
      cytometric bead array. RESULTS: Trichuris and Ascaris infections were linked to
      increased frequencies of "activated" CD4 and/or CD8 T cells (p<0.05), whereas
      Hookworm infection was associated with a trend towards decreased HLA-DR+ CD8 T
      cell frequencies (p = 0.222). In Trichuris infected subjects, there was a linear
      correlation between HLA-DR+ CD4 T cell frequencies and the cytokines IL-1beta and
      IL-10 (p<0.05). Helminth treatment with Albendazole and Praziquantel
      significantly decreased eosinophilia for S. mansoni and Hookworm infections
      (p<0.005) but not for Trichuris infection and only moderately modulated T cell
      activation. CCR5 surface density on memory CD4 T cells was increased by 1.2-fold
      during Trichuris infection (p-value: 0.053) and reduced after treatment (p =
      0.003). CONCLUSIONS: Increased expression of T cell activation markers was
      associated with Trichuris and Ascaris infections with relatively little effect of
      helminth treatment.

PMID- 24675896
TI  - Global quantitative modeling of chromatin factor interactions.
AB  - Chromatin is the driver of gene regulation, yet understanding the molecular
      interactions underlying chromatin factor combinatorial patterns (or the
      "chromatin codes") remains a fundamental challenge in chromatin biology. Here we
      developed a global modeling framework that leverages chromatin profiling data to
      produce a systems-level view of the macromolecular complex of chromatin. Our
      model ultilizes maximum entropy modeling with regularization-based structure
      learning to statistically dissect dependencies between chromatin factors and
      produce an accurate probability distribution of chromatin code. Our unsupervised
      quantitative model, trained on genome-wide chromatin profiles of 73 histone marks
      and chromatin proteins from modENCODE, enabled making various data-driven
      inferences about chromatin profiles and interactions. We provided a highly
      accurate predictor of chromatin factor pairwise interactions validated by known
      experimental evidence, and for the first time enabled higher-order interaction
      prediction. Our predictions can thus help guide future experimental studies. The
      model can also serve as an inference engine for predicting unknown chromatin
      profiles--we demonstrated that with this approach we can leverage data from well
      characterized cell types to help understand less-studied cell type or conditions.

PMID- 24675897
TI  - Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells
      and its growth promoting activity.
AB  - Makorin-2 (MKRN2) is a highly conserved protein and yet its functions are largely
      unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and
      malignant hematopoietic cells, and leukemia cell lines. We also attempted to
      delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells
      and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus
      transduction and shRNA nucleofection, respectively. Our results provided the
      first evidence on the ubiquitous expression of MKRN2 in normal hematopoietic
      cells, embryonic stem cell lines, primary leukemia and leukemic cell lines of
      myeloid, lymphoid, erythroid and megakaryocytic lineages. The expression levels
      of MKRN2 were generally higher in primary leukemia samples compared with those in
      age-matched normal BM cells. In all leukemia subtypes, there was no significant
      correlation between expression levels of MKRN2 and RAF1. sh-MKRN2-silenced CD34+
      cells had a significantly lower proliferation capacity and decreased levels of
      the early stem/progenitor subpopulation (CFU-GEMM) compared with control
      cultures. Over-expression of MKRN2 in K562 cells increased cell proliferation.
      Our results indicated possible roles of MKRN2 in normal and malignant
      hematopoiesis. 

PMID- 24675898
TI  - MicroRNA-424 is down-regulated in hepatocellular carcinoma and suppresses cell
      migration and invasion through c-Myb.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related
      mortality worldwide. MicroRNAs (miRNAs) are important regulators of multiple
      cellular processes, and the aberrant miRNAs expressions have been observed in
      different types of cancer including HCC. Their pathysiologic role and their
      relevance to tumorigenesis are still largely unknown. In this study, we
      demonstrated the down-regulation of miR-424 in HCC cell lines and tissues by
      quantitative RT-PCR analyses. Overexpression of miR-424 reduced the HCC cell
      prolifetation, migration, and invasion. Conversely, inhibiton of miR-424
      expression significantly accelerated the cell proliferation, migration, and
      invasion. In addition, we further identified c-Myb as a functional downstream
      target of miR-424 by directly targeting the 3'UTR of c-Myb. Furthermore,
      overexpression of c-Myb impaired miR-424-induced inhibition of proliferation and
      invasion in HCC cells. Our results demonstrated that miR-424 was involved in
      tumorigenesis of HCC at least in part by suppression of c-Myb. 

PMID- 24675899
TI  - Fungal infection intensity and zoospore output of Atelopus zeteki, a potential
      acute chytrid supershedder.
AB  - Amphibians vary in their response to infection by the amphibian-killing chytrid
      fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the
      first to decline and/or disappear once Bd arrives at a site. These competent
      hosts likely facilitate Bd proliferation because of ineffective innate and/or
      acquired immune defenses. We show that Atelopus zeteki, a highly susceptible
      species that has undergone substantial population declines throughout its range,
      rapidly and exponentially increases skin Bd infection intensity, achieving
      intensities that are several orders of magnitude greater than most other species
      reported. We experimentally infected individuals that were never exposed to Bd (n
      = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within
      seven days post-inoculation, the average Bd infection intensity was 18,213
      zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity
      and zoospore output (i.e., the number of zoospores released per minute by an
      infected individual) increased exponentially until time of death (t50 = 7.018,
      p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and
      zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55
      zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158
      zoospores on a single individual. The daily percent increases in Bd infection
      intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04),
      respectively. We also found that Bd infection intensity and zoospore output were
      positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33
      days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect
      on survival, Bd infection intensity, or zoospore output. We conclude that A.
      zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our
      results can inform epidemiological models to estimate Bd outbreak probability,
      especially as they relate to reintroduction programs.

PMID- 24675900
TI  - Alpha, beta and gamma diversity differ in response to precipitation in the Inner
      Mongolia grassland.
AB  - Understanding the distribution pattern and maintenance mechanism of species
      diversity along environmental gradients is essential for developing biodiversity
      conservation strategies under environmental change. We have surveyed the species
      diversity at 192 vegetation sites across different steppe zones in Inner
      Mongolia, China. We analysed the total species diversity (gamma diversity) and
      its composition (alpha diversity and beta diversity) of different steppe types,
      and their changes along a precipitation gradient. Our results showed that (i)
      beta diversity contributed more than alpha diversity to the total (gamma)
      diversity in the Inner Mongolia grassland; the contribution of beta diversity
      increased with precipitation, thus the species-rich (meadow steppe) grassland had
      greater contribution of beta diversity than species-poor (desert steppe)
      grassland. (ii) All alpha, beta and gamma species diversity increased
      significantly (P<0.05) with precipitation, but their sensitivity to precipitation
      (diversity change per mm precipitation increase) was different between the steppe
      types. The sensitivity of alpha diversity of different steppe community types was
      negatively (P<0.05) correlated with mean annual precipitation, whereas the
      sensitivity of beta and gamma diversity showed no trend along the precipitation
      gradient (P>0.10). (iii) The alpha diversity increased logarithmically, while
      beta diversity increased exponentially, with gamma diversity. Our results suggest
      that for local species diversity patterns, the site species pool is more
      important in lower precipitation areas, while local ecological processes are more
      important in high precipitation areas. In addition, for beta diversity
      maintenance niche processes and diffusion processes are more important in low and
      high precipitation areas, respectively. Our results imply that a policy of
      "multiple small reserves" is better than one of a "single large reserve" for
      conserving species diversity of a steppe ecosystem, and indicate an urgent need
      to develop management strategies for climate-sensitive desert steppe ecosystem. 

PMID- 24675901
TI  - Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle.
AB  - The domestication and development of cattle has considerably impacted human
      societies, but the histories of cattle breeds and populations have been poorly
      understood especially for African, Asian, and American breeds. Using genotypes
      from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543
      animals, we evaluate the population structure of 134 domesticated bovid breeds.
      Regardless of the analytical method or sample subset, the three major groups of
      Asian indicine, Eurasian taurine, and African taurine were consistently observed.
      Patterns of geographic dispersal resulting from co-migration with humans and
      exportation are recognizable in phylogenetic networks. All analytical methods
      reveal patterns of hybridization which occurred after divergence. Using 19
      breeds, we map the cline of indicine introgression into Africa. We infer that
      African taurine possess a large portion of wild African auroch ancestry, causing
      their divergence from Eurasian taurine. We detect exportation patterns in Asia
      and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also
      identify the influence of species other than Bos taurus taurus and B. t. indicus
      in the formation of Asian breeds. We detect the pronounced influence of Shorthorn
      cattle in the formation of European breeds. Iberian and Italian cattle possess
      introgression from African taurine. American Criollo cattle originate from
      Iberia, and not directly from Africa with African ancestry inherited via Iberian
      ancestors. Indicine introgression into American cattle occurred in the Americas,
      and not Europe. We argue that cattle migration, movement and trading followed by
      admixture have been important forces in shaping modern bovine genomic variation. 

PMID- 24675902
TI  - Two-component system cross-regulation integrates Bacillus anthracis response to
      heme and cell envelope stress.
AB  - Two-component signaling systems (TCSs) are one of the mechanisms that bacteria
      employ to sense and adapt to changes in the environment. A prototypical TCS
      functions as a phosphorelay from a membrane-bound sensor histidine kinase (HK) to
      a cytoplasmic response regulator (RR) that controls target gene expression.
      Despite significant homology in the signaling domains of HKs and RRs, TCSs are
      thought to typically function as linear systems with little to no cross-talk
      between non-cognate HK-RR pairs. Here we have identified several cell envelope
      acting compounds that stimulate a previously uncharacterized Bacillus anthracis
      TCS. Furthermore, this TCS cross-signals with the heme sensing TCS HssRS;
      therefore, we have named it HssRS interfacing TCS (HitRS). HssRS reciprocates
      cross-talk to HitRS, suggesting a link between heme toxicity and cell envelope
      stress. The signaling between HssRS and HitRS occurs in the parental B. anthracis
      strain; therefore, we classify HssRS-HitRS interactions as cross-regulation.
      Cross-talk between HssRS and HitRS occurs at both HK-RR and post-RR signaling
      junctions. Finally, HitRS also regulates a previously unstudied ABC transporter
      implicating this transporter in the response to cell envelope stress. This
      chemical biology approach to probing TCS signaling provides a new model for
      understanding how bacterial signaling networks are integrated to enable
      adaptation to complex environments such as those encountered during colonization
      of the vertebrate host. 

PMID- 24675904
TI  - A solar-thermal energy harvesting scheme: enhanced heat capacity of molten HITEC
      salt mixed with Sn/SiO(x) core-shell nanoparticles.
AB  - We demonstrated enhanced solar-thermal storage by releasing the latent heat of
      Sn/SiO(x) core-shell nanoparticles (NPs) embedded in a eutectic salt. The
      microstructures and chemical compositions of Sn/SiO(x) core-shell NPs were
      characterized. In situ heating XRD provides dynamic crystalline information about
      the Sn/SiO(x) core-shell NPs during cyclic heating processes. The latent heat of
      ~29 J g(-1) for Sn/SiO(x) core-shell NPs was measured, and 30% enhanced heat
      capacity was achieved from 1.57 to 2.03 J g(-1) K(-1) for the HITEC solar salt
      without and with, respectively, a mixture of 5% Sn/SiO(x) core-shell NPs. In
      addition, an endurance cycle test was performed to prove a stable operation in
      practical applications. The approach provides a method to enhance energy storage
      in solar-thermal power plants.

PMID- 24675903
TI  - Neuronal spike timing adaptation described with a fractional leaky integrate-and
      fire model.
AB  - The voltage trace of neuronal activities can follow multiple timescale dynamics
      that arise from correlated membrane conductances. Such processes can result in
      power-law behavior in which the membrane voltage cannot be characterized with a
      single time constant. The emergent effect of these membrane correlations is a non
      Markovian process that can be modeled with a fractional derivative. A fractional
      derivative is a non-local process in which the value of the variable is
      determined by integrating a temporal weighted voltage trace, also called the
      memory trace. Here we developed and analyzed a fractional leaky integrate-and
      fire model in which the exponent of the fractional derivative can vary from 0 to
      1, with 1 representing the normal derivative. As the exponent of the fractional
      derivative decreases, the weights of the voltage trace increase. Thus, the value
      of the voltage is increasingly correlated with the trajectory of the voltage in
      the past. By varying only the fractional exponent, our model can reproduce upward
      and downward spike adaptations found experimentally in neocortical pyramidal
      cells and tectal neurons in vitro. The model also produces spikes with longer
      first-spike latency and high inter-spike variability with power-law distribution.
      We further analyze spike adaptation and the responses to noisy and oscillatory
      input. The fractional model generates reliable spike patterns in response to
      noisy input. Overall, the spiking activity of the fractional leaky integrate-and
      fire model deviates from the spiking activity of the Markovian model and reflects
      the temporal accumulated intrinsic membrane dynamics that affect the response of
      the neuron to external stimulation. 

PMID- 24675905
TI  - Synthesis of o-chlorophenols via an unexpected nucleophilic chlorination of
      quinone monoketals mediated by N,N'-dimethylhydrazine dihydrochloride.
AB  - An unexpected nucleophilic chlorination of a quinone monoketal while carrying out
      a pyrazolidine synthesis has led to a general preparation of multisubstituted
      phenols. The products are obtained in good to high yields under mild conditions.
      The bridged pyrazolidines that were the original targets are obtained in the
      presence of a protic solvent. 

PMID- 24675906
TI  - Network formation in graphene oxide composites with surface grafted PNIPAM chains
      in aqueous solution characterized by rheological experiments.
AB  - Poly N-isopropyl acrylamide (PNI) radically polymerized in aqueous solution in
      the presence of graphene oxide (GO) can significantly change the properties of
      the resulting solution from a regular polymer solution to a soft solid with a GO
      content of only 0.176 wt% (3 wt% with respect to PNI). However, these properties
      require the presence of both grafting and supramolecular interactions between
      polymer chains and hydrophilic groups on GO (-OH, -COOH), proven by Fourier
      transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X
      ray diffraction and spectroscopy (XRD) and Raman spectra. While very low GO
      contents (below 0.05 wt%) only lead to a labile structure, which can be
      disassembled by shear, higher contents yield composites with solid-like
      characteristics. This is clearly evident from the rheological behaviour, which
      changes significantly at a GO content around 0.15 wt%. Intensive shearing
      destroys the weak network, which cannot reform quickly at lower GO
      concentrations, while at intermediate concentrations, restructuring is fast. GO
      contents of 0.176 wt% lead to a material behaviour, which almost perfectly
      recovers from small deformations (creep and creep recovery compliance almost
      match) but larger deformations lead to permanent damage to the sample. 

PMID- 24675907
TI  - Respiratory muscle endurance is limited by lower ventilatory efficiency in post
      myocardial infarction patients.
AB  - BACKGROUND: Reduced respiratory muscle endurance (RME) contributes to increased
      dyspnea upon exertion in patients with cardiovascular disease. OBJECTIVE: The
      objective was to characterize ventilatory and metabolic responses during RME
      tests in post-myocardial infarction patients without respiratory muscle weakness.
      METHOD: Twenty-nine subjects were allocated into three groups: recent myocardial
      infarction group (RG, n=9), less-recent myocardial infarction group (LRG, n=10),
      and control group (CG, n=10). They underwent two RME tests (incremental and
      constant pressure) with ventilatory and metabolic analyses. One-way ANOVA and
      repeated measures one-way ANOVA, both with Tukey post-hoc, were used between
      groups and within subjects, respectively. RESULTS: Patients from the RG and LRG
      presented lower metabolic equivalent and ventilatory efficiency than the CG on
      the second (50+/- 06, 50+/- 5 vs. 42+/- 4) and third part (50+/- 11, 51+/- 10 vs.
      43+/- 3) of the constant pressure RME test and lower metabolic equivalent during
      the incremental pressure RME test. Additionally, at the peak of the incremental
      RME test, RG patients had lower oxygen uptake than the CG. CONCLUSIONS: Post
      myocardial infarction patients present lower ventilatory efficiency during
      respiratory muscle endurance tests, which appears to explain their inferior
      performance in these tests even in the presence of lower pressure overload and
      lower metabolic equivalent.

PMID- 24675908
TI  - Cardiac autonomic responses during upper versus lower limb resistance exercise in
      healthy elderly men.
AB  - OBJECTIVE: To investigate the cardiac autonomic responses during upper versus
      lower limb discontinuous resistance exercise (RE) at different loads in healthy
      older men. METHOD: Ten volunteers (65+/-1.2 years) underwent the one-repetition
      maximum (1RM) test to determine the maximum load for the bench press and the leg
      press. Discontinuous RE was initiated at a load of 10%1RM with subsequent
      increases of 10% until 30%1RM, followed by increases of 5%1RM until exhaustion.
      Heart rate (HR) and R-R interval were recorded at rest and for 4 minutes at each
      load applied. Heart rate variability (HRV) was analyzed in 5-min segments at rest
      and at each load in the most stable 2-min signal. RESULTS: Parasympathetic
      indices decreased significantly in both exercises from 30%1RM compared to rest
      (rMSSD: 20+/-2 to 11+/-3 and 29+/-5 to 12+/-2 ms; SD1: 15+/-2 to 8+/-1 and 23+/-4
      to 7+/-1 ms, for upper and lower limb exercise respectively) and HR increased
      (69+/-4 to 90+/-4 bpm for upper and 66+/-2 to 89+/-1 bpm for lower). RMSM
      increased for upper limb exercise, but decreased for lower limb exercise (28+/-3
      to 45+/-9 and 34+/-5 to 14+/-3 ms, respectively). In the frequency domain, the
      sympathetic (LF) and sympathovagal balance (LF/HF) indices were higher and the
      parasympathetic index (HF) was lower for upper limb exercise than for lower limb
      exercise from 35% of 1RM. CONCLUSIONS: Cardiac autonomic change occurred from 30%
      of 1RM regardless of RE limb. However, there was more pronounced sympathetic
      increase and vagal decrease for upper limb exercise than for lower limb exercise.
      These results provide a basis for more effective prescription of RE to promote
      health in this population.

PMID- 24675909
TI  - Body posture changes in women with migraine with or without temporomandibular
      disorders.
AB  - BACKGROUND: Migraine and temporomandibular disorders (TMDs) are reported to be
      associated. However, there are no reports on the association among migraines,
      TMDs and changes in body posture. OBJECTIVES: To assess changes in body posture
      in women suffering migraines with or without TMD compared with a control group.
      METHOD: Sixty-six women with a mean age of 18 to 45 years participated in this
      study. The groups were composed of 22 volunteers with migraine and TMD (MTMD), 22
      volunteers with migraines without TMD (MG) and 22 women in the control group
      (CG). Static posture was assessed by photogrammetry, and 19 angles were measured.
      RESULTS: Postural asymmetry was observed in the face for 4 angles measured on the
      frontal plane in the MG group and for 4 angles of the trunk in the MG and MTMD
      groups with respect to CG. However, for comparisons between MTMD and CG, clinical
      relevance was identified for two angles of the sagittal plane (Cervical and
      Lumbar Lordosis, Effect Size - ES - moderate: 0.53 and 0.60). For comparisons
      between the MG and CG, the clinical relevance/potential was verified for three
      angles with moderate ES (ES>0.42). The clinical relevance when comparing MTMD and
      CG was identified for four angles of facial symmetry head inclination (ES>0.54)
      and for two angles between MG and CG (ES>0.48). CONCLUSION: The results
      demonstrated the presence of postural changes compared with a control group in
      women with migraines with or without TMD, and there were similar clinically
      relevant postural changes among the patients with migraines with and without TMD.

PMID- 24675910
TI  - The influence of resistance exercise with emphasis on specific contractions
      (concentric vs. eccentric) on muscle strength and post-exercise autonomic
      modulation: a randomized clinical trial.
AB  - BACKGROUND: Compared to eccentric contractions, concentric contractions result in
      higher cardiovascular stress. However, we do not know how these two types of
      contractions influence cardiac autonomic modulation during the post-exercise
      recovery period. OBJECTIVE: to compare the effect of resistance training that is
      performed with concentric vs. eccentric emphasis on muscle strength and on post
      exercise recovery which was assessed by examining heart rate variability (HRV),
      for the knee extensor muscle group in young healthy adults. METHODS: For this
      study, 105 men between 18 and 30 years of age were randomized into 4 groups:
      concentric control (CONCC), eccentric control (ECCC), concentric training (CONCT)
      and eccentric training (ECCT). The CONCC and ECCC groups underwent one session of
      resistance exercise (RE) using the knee extensor muscle group (3 sets of 1
      repetition at 100% of the maximal repetition [1MR]) and the CONCT and ECCT groups
      performed 10 training sessions. The HRV was analyzed at baseline and across four
      recovery periods (T1, T2, T3 and T4). RESULTS: The ECCT group exhibited increased
      muscle strength at the end of the study. Regarding cardiac autonomic modulation,
      the CONCC and ECCC groups exhibited increases in overall variability (SDNN and
      SD2) at T1 compared to baseline, and the ECCT group demonstrated increases in
      variables reflecting vagal modulation and the recovery process (RMSSD, SD1 and HF
      [ms2]) at T1, T2 and T4 compared to baseline. CONCLUSIONS: Resistance training
      with emphasis on eccentric contractions promoted strength gain and an increase in
      cardiac vagal modulation during recovery compared to baseline.

PMID- 24675911
TI  - Combined exercise circuit session acutely attenuates stress-induced blood
      pressure reactivity in healthy adults.
AB  - OBJECTIVE: To investigate the blood pressure (BP) responses to cardiovascular
      stress test after a combined exercise circuit session at moderate intensity.
      METHOD: Twenty individuals (10 male/10 fem; 33.4+/- 6.9 years; 70.2+/- 15.8 kg;
      170.4+/- 11.5 cm; 22.3+/- 6.8% body fat) were randomized in a different days to
      control session with no exercise or exercise session consisting of 3 laps of the
      following circuit: knee extension, bench press, knee flexion, rowing in the prone
      position, squats, shoulder press, and 5 min of aerobic exercise at 75-85% of age
      predicted maximum heart rate and/or 13 on the Borg Rating of Perceived Exertion
      [scale of 6 to 20]. The sets of resistance exercise consisted of 15 repetitions
      at ~50% of the estimated 1 repetition maximum test. Systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) were measured at rest and during 1h of
      recovery in both experimental sessions. After that, blood pressure reactivity
      (BPR) was evaluated using the Cold Pressor Test. RESULTS: During 1h of exercise
      recovery, there was a reduction in SBP (3-6 mmHg) and DBP (2-5 mmHg) in relation
      to pre-session rest (p<0.01), while this reduction was not observed in the
      control session. A decline in BPR (4-7 mmHg; p<0.01) was observed 1h post
      exercise session, but not in the control session. Post-exercise reductions in SBP
      and DBP were significantly correlated with BPR reductions (r=0.50-0.45; p<0.05).
      CONCLUSION: A combined exercise circuit session at moderate intensity promoted
      subsequent post-exercise hypotension and acutely attenuated BPR in response to a
      cardiovascular stress test. In addition, the post-exercise BP reduction was
      correlated with BPR attenuation in healthy adults of both genders.

PMID- 24675912
TI  - Endothelial wall thickness, cardiorespiratory fitness and inflammatory markers in
      obese and non-obese adolescents.
AB  - BACKGROUND: Increased carotid intima-media thickness (c-IMT) is considered a
      marker of early-onset atherosclerosis and it has been found in obese children and
      adolescents, but the risk factors associated with this population remain to be
      elucidated. OBJECTIVE: To compare and verify the relationship between c-IMT,
      metabolic profile, inflammatory markers, and cardiorespiratory fitness in obese
      and non-obese children and adolescents. METHOD: Thirty-five obese subjects (19
      boys) and 18 non-obese subjects (9 boys), aged 10-16 years, were included.
      Anthropometry, body composition, blood pressure, maximal oxygen consumption
      (VO2max), and basal metabolic rate were evaluated. Serum glucose, insulin,
      homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, C
      reactive protein (CRP), and adiponectin were assessed. c-IMT was measured by
      ultrasound. RESULTS: The results showed that c-IMT, triglycerides, insulin, HOMA
      IR, and CRP values were significantly higher in the obese group than in the non
      obese group, and high-density lipoprotein cholesterol (HDL-c), adiponectin, and
      VO2max values were significantly lower in the obese group than in the non-obese
      group. The c-IMT was directly correlated with body weight, waist circumference, %
      body fat, and HOMA-IR and inversely correlated with % free fat mass, HDL-c, and
      VO2max. CONCLUSIONS: Our findings show that c-IMT correlates not only with body
      composition, lipids, insulin resistance, and inflammation but also with low
      VO2max values in children and adolescents.

PMID- 24675913
TI  - Description of research design of articles published in four Brazilian physical
      therapy journals.
AB  - BACKGROUND: While the research design of articles published in medical journals
      and in some physical therapy journals has already been evaluated, this has not
      been investigated in Brazilian physical therapy journals. Objective : To describe
      the research design used in all articles published in Brazilian scientific
      journals that are freely available, have high Qualis rankings, and are relevant
      to physical therapy over a 7-year period. METHOD: We extracted the bibliometric
      data, research design, research type (human or animal), and clinical area for all
      articles published. The articles were grouped into their level of evidence, and
      descriptive analyses were performed. We calculated the frequency, proportions of
      articles, and 95% confidence interval of these proportions with each research
      design in each journal. We cross-tabulated the clinical areas with research
      designs (expressed as number and percentages). RESULTS: A total of 1,458 articles
      from four Brazilian journals were found: Revista Brasileira de Fisioterapia,
      Revista Fisioterapia em Movimento, Revista Fisioterapia e Pesquisa, and Revista
      Acta Fisiatrica. The majority of articles were classified as level II of evidence
      (60%), followed by level III (29%) and level I (10%). The most prevalent research
      designs were cross-sectional studies (38%), single-case or case-series studies,
      and narrative reviews. Most articles reported human research and were in the
      musculoskeletal, neurologic, and cardiothoracic areas. CONCLUSIONS: Most of the
      research published in Brazilian physical therapy journals used levels II and III
      of evidence. Increasing the publication rate of systematic reviews and randomized
      controlled trials would provide more high-quality evidence to guide evidence
      based physical therapy practice.

PMID- 24675914
TI  - Functional outcomes in patients with chronic obstructive pulmonary disease: a
      multivariate analysis.
AB  - BACKGROUND: Multiple factors can influence the severity of chronic obstructive
      pulmonary disease (COPD) and the functioning of patients with COPD, such as
      personal characteristics and systemic manifestations. OBJECTIVE: To evaluate the
      different factors that can influence the activity and psychosocial impact domains
      of the Saint George's Respiratory Questionnaire (SGRQ) in COPD patients. METHOD:
      Participants, recruited in a university-based hospital, responded to the SGRQ,
      and in addition, personal, anthropometric, and clinical data were collected. The
      study was approved by the Institutional Ethics Committee. Data were analyzed
      using multiple linear regression models, with the SGRQ activity and psychosocial
      impact scores as outcome variables, and 10 explanatory variables (age, gender,
      forced expiratory volume in the first second - FEV1, smoking load, body mass
      index, oxygen therapy, associated diseases, regular physical activity,
      participation in a formal rehabilitation program, and SGRQ symptoms score) were
      considered. RESULTS: The best regression model for predicting the SGRQ activity
      score (r2=0.477) included gender, FEV1, and SGRQ symptoms. In contrast, the
      predictive model with the highest proportion of explained variance in
      psychosocial impact score (r2=0.426) included the variables gender, oxygen
      therapy, and SGRQ symptoms. CONCLUSIONS: The results indicate that the outcomes,
      while based on functioning parameters in COPD patients, could be partly explained
      by the personal and clinical factors analyzed, especially by the symptoms
      assessed by the SGRQ. Thus, it appears that the health conditions of these
      patients cannot be described by isolated variables, including pulmonary function
      parameters.

PMID- 24675915
TI  - Low and high-frequency TENS in post-episiotomy pain relief: a randomized, double
      blind clinical trial.
AB  - OBJECTIVE: To evaluate the effectiveness of low-frequency TENS (LFT) and high
      frequency TENS (HFT) in post-episiotomy pain relief. METHOD: A randomized,
      controlled, double-blind clinical trial with placebo composed of 33 puerperae
      with post-episiotomy pain. TENS was applied for 30 minutes to groups: HFT(100 Hz;
      100 us), LFT (5 Hz; 100 us), and placebo (PT). Four electrodes were placed in
      parallel near the episiotomy and four pain evaluations were performed with the
      numeric rating scale. The first and the second evaluation took place before TENS
      application and immediately after its removal and were done in the resting
      position and in the activities of sitting and ambulating. The third and fourth
      evaluation took place 30 and 60 minutes after TENS removal, only in the resting
      position. Intragroup differences were verified using the Friedman and Wilcoxon
      tests, and the intergroup analysis employed the Kruskal-Wallis test. RESULTS: In
      the intragroup analysis, there was no significant difference in the PT during
      rest, sitting, and ambulation (P>0.05). In the HFT and LFT, a significant
      difference was observed in all activities (P<0.001). In the intergroup analysis,
      there was a significant difference in the resting position in the HFT and LFT
      (P<0.001). In the sitting activity, a significant difference was verified in the
      second evaluation in the HFT and LFT (P<0.008). No significant difference was
      verified among the groups in ambulation (P<0.20). CONCLUSIONS: LFT and HFT are an
      effective resource that may be included in the routine of maternity wards.

PMID- 24675916
TI  - Lung function and six-minute walk test performance in individuals with sickle
      cell disease.
AB  - BACKGROUND: Sickle Cell Disease (SCD), which is characterized by a mutation in
      the gene encoding beta hemoglobin, causes bodily dysfunctions such as impaired
      pulmonary function and reduced functional capacity. OBJECTIVE: To assess changes
      in pulmonary function and functional capacity in patients with SCD and to
      identify the relationships between these variables. METHOD: We evaluated
      sociodemographic, anthropometric, lung function (spirometry), respiratory
      (manovacuometer), peripheral muscle strength (Handgrip strength - HS) and
      functional capacity (i.e., the six-minute walk test) parameters in 21 individuals
      with SCD (average age of 29+/-6 years). Shapiro-Wilk, paired Student's, Wilcoxon,
      Pearson and Spearman correlation tests were used for statistical analyses, and
      the significance threshold was set at p<0.05. RESULTS: A total of 47.6% of the
      study subjects exhibited an altered ventilation pattern, 42.8% had a restrictive
      ventilatory pattern (RVP) and 4.8% exhibited a mixed ventilatory pattern (MVP).
      The observed maximal inspiratory pressure (MIP) values were below the predicted
      values for women (64 cmH2O), and the maximum expiratory pressure (MEP) values, HS
      values and distance walked during the 6MWT were below the predicted values for
      both men (103 cmH2O, 39 Kgf and 447 m, respectively) and women (64 cmH2O; 27 Kgf;
      405 m, respectively). Positive correlations were observed between maximum
      voluntary ventilation (MVV) and MEP (r=0.4; p=0.046); MVV and BMI (r=0.6;
      p=0.003); and between HS and MIP (r=0.7; p=0.001), MEP (r=0.6; p=0.002), MVV
      (r=0.5; p=0.015), distance walked in the 6MWT (r=0.4; p=0.038) and BMI (r=0.6;
      p=0.004). CONCLUSIONS : SCD promoted changes in lung function and functional
      capacity, including RVPs and a reduction in the distance walked in the 6MWT when
      compared to the predictions. In addition, significant correlations between the
      variables were observed.

PMID- 24675917
TI  - Citations of Brazilian physical therapy journals in national publications.
AB  - BACKGROUND: Quotations in Brazilian journals are mainly obtained from national
      articles (articles from Brazilian journals); thus, it is essential to determine
      how frequently these articles reference Brazilian journals. OBJECTIVE: This study
      sought to verify how frequently national papers are cited in the references of
      three Brazilian physical therapy journals. METHOD: All references for articles
      published in Fisioterapia em Movimento, Fisioterapia e Pesquisa and Revista
      Brasileira de Fisioterapia between 2010 and 2012 were evaluated. In particular,
      the numbers of national articles and international articles (articles from
      international journals) cited in these references were determined. RESULTS: A
      total of 13,009 references cited by 456 articles were analyzed, and 2,924
      (22.47%) of the cited works were national articles. There were no significant
      differences among the three examined years. A total of 36 (7.89%) articles did
      not cite national articles, whereas 65 (13.25%) articles cited more national
      articles than international articles. CONCLUSION: On average, 22.47% of the works
      cited by the evaluated articles were national articles. No significant
      differences were detected among the three analyzed years.

PMID- 24675919
TI  - The influence of radioactive decay on actinide magnetic susceptibility
      measurements obtained using the Evans method.
AB  - In order to explain the higher magnetic susceptibility of some aquo actinide ions
      than predicted by Hund's rules, the molar magnetic susceptibilities of two
      americium isotopes ((241)Am and (243)Am) were measured using the Evans method.
      The results obtained show a growing change in the magnetic susceptibility with
      alpha and also a beta(-) activity increase in solution. beta(-) particle effects
      appear to be stronger than radicals formed by alpha particles on the experimental
      values. The temperature dependence of Am(iii) magnetic susceptibility has been
      observed but from experiments carried out here, it appears to be difficult to
      prove whether this effect arises from radicals or beta(-). Finally, magnetic
      susceptibilities of americium recorded in different media (HClO4, HCl, and HNO3)
      have been compared to alpha and beta emissions' impact. 

PMID- 24675918
TI  - Cold water immersion of the ankle decreases neuromuscular response of lower limb
      after inversion movement.
AB  - BACKGROUND: Cryotherapy has been associated with a significant decrease in nerve
      conduction velocity and muscle contraction with possible effects on exercise and
      physical training. OBJECTIVES: To quantify the electromyographic response of the
      lateral gastrocnemius, tibialis anterior, fibularis longus, rectus femoris and
      gluteus medius to ankle inversion following cold water immersion. METHOD: The
      peak values of the root mean square (RMS) were obtained from 35 healthy and
      active university subjects after the use of a tilt platform to force the ankle
      into 30 degrees  of inversion before, immediately after, and 10, 20, and 30
      minutes after water immersion at 4+/-2 degrees C, for 20 minutes. The Shapiro
      Wilk test, repeated measures analysis, Bonferroni's post-hoc, and linear
      regression analysis provided the results. RESULTS: Peak RMS was significantly
      lower at all times after cold water immersion, with residual effect of up to 30
      minutes, when compared to pre-immersion for all muscles, except for immediate
      post-immersion for the gluteus medius. CONCLUSIONS: After cold water immersion of
      the ankle, special care should be taken in activities that require greater
      neuromuscular control.

PMID- 24675920
TI  - Sensory neurons and osteoblasts: close partners in a microfluidic platform.
AB  - Innervation has proven to be critical in bone homeostasis/regeneration due to the
      effect of soluble factors, produced by nerve fibers, associated with changes in
      the activity of bone cells. Thus, in this study, we have established and
      characterized a coculture system comprising sensory neurons and osteoblasts to
      mimic the in vivo scenario where nerve fibers can be found in a bone
      microenvironment. Embryonic or adult primary dorsal root ganglion (DRG) and MC3T3
      E1 osteoblastic cells were cocultured in compartmentalized microfluidic platforms
      and morphological and functional tests were performed. The time of adhesion and
      readout of axonal outgrowth were improved by the alignment of DRG with the axis
      of microgrooves, which showed to be a crucial step for the designed experiments.
      Cocultures of entire DRG from adult origin with osteoblasts were performed,
      showing extended DRG projections towards the axonal compartment, reaching
      osteoblastic cells. Immunocytochemistry showed that the neurites present within
      the osteoblastic compartment were immunoreactive to synapsin and calcitonin gene
      related peptide suggesting the presence of specialized structures involved in
      this crosstalk. This evidence was further confirmed by electron microscopy where
      varicosities were detected as well as electron dense structures in neurite
      membranes. Aiming to mimic the properties of tissue extracellular matrices, MC3T3
      E1 cells were seeded in the axonal side upon laminin, collagen or within 3D
      functionalized alginate matrices and axonal outgrowth was clearly observed. In
      order to analyze and quantify data with reproducible image analysis, a semi
      automated algorithm was also developed. The collagen and laminin substrates
      displayed a higher amount of axons reaching the axonal side. Overall, the
      established method revealed to be a suitable tool to study the interaction
      between the peripheral nervous system and bone cells in different contexts
      mimicking the in vivo scenario. 

PMID- 24675921
TI  - Exogenous expression of marine lectins DlFBL and SpRBL induces cancer cell
      apoptosis possibly through PRMT5-E2F-1 pathway.
AB  - Lectins are widely existed in marine bioresources, and some purified marine
      lectins were found toxic to cancer cells. In this report, genes encoding
      Dicentrarchus labrax fucose-binding lectin (DlFBL) and Strongylocentrotus
      purpuratus rhamnose-binding lectin (SpRBL) were inserted into an adenovirus
      vector to form Ad.FLAG-DlFBL and Ad.FLAG-SpRBL, which elicited significant in
      vitro suppressive effect on a variety of cancer cells. Anti-apoptosis factors Bcl
      2 and XIAP were determined to be downregulated by Ad.FLAG-DlFBL and Ad.FLAG
      SpRBL. Subcellular localization studies showed that DlFBL but not SpRBL widely
      distributed in membrane systems. Both DlFBL and SpRBL were shown associated with
      protein arginine methyltransferase 5 (PRMT5), and PRMT5-E2F-1 pathway was
      suggested to be responsible for the DlFBL and SpRBL induced apoptosis. Further
      investigations revealed that PRMT5 acted as a common binding target for various
      exogenous lectin and non-lectin proteins, suggesting a role of PRMT5 as a barrier
      for foreign gene invasion. The cellular response to exogenous lectins may provide
      insights into a novel way for cancer gene therapy. 

PMID- 24675923
TI  - Breast cancer--thinking globally.

PMID- 24675928
TI  - Environmental science. China gets serious about its pollutant-laden soil.

PMID- 24675922
TI  - How and when should NSAIDs be used for preventing post-ERCP pancreatitis? A
      systematic review and meta-analysis.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be
      efficacious to prevent pancreatitis after endoscopic retrograde
      cholangiopancreatography (ERCP). However, the target patients, the type of NSAID,
      the route of administration and the time of drug delivery remain unclear, as well
      as the potential efficacy in reducing the severity of pancreatitis, length of
      hospital stay and mortality. The objective of the study was to evaluate these
      questions by performing a systematic review and meta-analysis. METHODS: Multiple
      searches were performed in the main databases. Randomized controlled trials
      (RCTs) comparing NSAIDs vs. placebo in the prevention of post-ERCP pancreatitis
      were included. Primary endpoint of the study was the efficacy for pancreatitis
      prevention. Sub-analyses were performed to determine the risk reduction in high
      and low risk patients, and to define optimal time, route of administration, and
      type of NSAID. Secondary endpoints were safety, moderate to severe pancreatitis
      prevention and reduction of hospital stay and mortality. RESULTS: Nine RCTs
      enrolling 2133 patients were included. The risk of pancreatitis was lower in the
      NSAID group than in the placebo group (RR 0.51; 95%CI 0.39-0.66). The number
      needed to treat was 14. The risk of moderate to severe pancreatitis was also
      lower in the NSAID group. (RR 0.46; 95%CI 0.28-0.76). No adverse events related
      to NSAID use were reported. NSAIDs were effective in both high-risk and
      unselected patients (RR 0.53; 95%CI 0.30-0.93 and RR 0.57; 95%CI 0.37-0.88). In
      the subanalyses, only rectal administration of either indomethacin (RR 0.54;
      95%CI 0.38-0.75) or diclofenac (RR 0.42; 95%CI 0.21-0.84) was shown to be
      effective. There were not enough data to perform a meta-analysis in hospital stay
      reduction. No deaths occurred. CONCLUSION: A single rectal dose of indomethacin
      or diclofenac before or immediately after ERCP is safe and prevents procedure
      related pancreatitis both in high risk and in unselected patients.

PMID- 24675929
TI  - Environment. 25 years after the Exxon Valdez, where are the herring?

PMID- 24675930
TI  - Human evolution. Oldest Homo sapiens genome pinpoints Neandertal input.

PMID- 24675931
TI  - Medicine. Pioneering womb transplant trial highlights risks and ethical dilemmas.

PMID- 24675932
TI  - Planetary science. Search for martian life clears another hurdle.

PMID- 24675933
TI  - Synthetic biology. Synthetic biologists design 'living materials' that build
      themselves.

PMID- 24675934
TI  - The camel connection.

PMID- 24675935
TI  - Building the ultimate yeast genome.

PMID- 24675936
TI  - Student assembly drives yeast project.

PMID- 24675937
TI  - Australia's drought: lessons for California.

PMID- 24675938
TI  - Drug trafficking's effects on coastal ecosystems.

PMID- 24675940
TI  - Citizen science. Next steps for citizen science.

PMID- 24675941
TI  - Immunology. The axis of tolerance.

PMID- 24675942
TI  - Astronomy. A different class of planets.

PMID- 24675943
TI  - Materials science. Why mineral interfaces matter.

PMID- 24675944
TI  - Biochemistry. The resolution revolution.

PMID- 24675945
TI  - Applied physics. Molecular tuning of quantum plasmon resonances.

PMID- 24675946
TI  - Cancer. Cholesterol and cancer, in the balance.

PMID- 24675947
TI  - Breast cancer. A race still unfinished. Introduction.

PMID- 24675948
TI  - Breast cancer. Breast cancer: a world of differences.

PMID- 24675949
TI  - Breast cancer. Dare to do less.

PMID- 24675950
TI  - Breast cancer. The 'other' breast cancer genes.

PMID- 24675951
TI  - Breast cancer. The advocate.

PMID- 24675952
TI  - "The race" to clone BRCA1.
AB  - The existence of BRCA1 was proven in 1990 by mapping predisposition to young
      onset breast cancer in families to chromosome 17q21. Knowing that such a gene
      existed and approximately where it lay triggered efforts by public and private
      groups to clone and sequence it. The press baptized the competition "the race"
      and reported on it in detail for the next 4 years. BRCA1 was positionally cloned
      in September 1994. Twenty years later, I reflect on "the race" and its
      consequences for breast cancer prevention and treatment. 

PMID- 24675953
TI  - Two decades after BRCA: setting paradigms in personalized cancer care and
      prevention.
AB  - The cloning of the breast cancer susceptibility genes BRCA1 and BRCA2 nearly two
      decades ago helped set in motion an avalanche of research exploring how genomic
      information can be optimally applied to identify and clinically care for
      individuals with a high risk of developing cancer. Genetic testing for mutations
      in BRCA1, BRCA2, and other breast cancer susceptibility genes has since proved to
      be a valuable tool for determining eligibility for enhanced screening and
      prevention strategies, as well as for identifying patients most likely to benefit
      from a targeted therapy. Here, we discuss the landscape of inherited mutations
      and sequence variants in BRCA1 and BRCA2, the complexities of determining disease
      risk when the pathogenicity of sequence variants is uncertain, and current
      strategies for clinical management of women who carry BRCA1/2 mutations. 

PMID- 24675954
TI  - Cancer suppression by the chromosome custodians, BRCA1 and BRCA2.
AB  - Germline mutations in BRCA1 and BRCA2 predispose to common human malignancies,
      most notably tumors of the breast and ovaries. The proteins encoded by these
      genes have been implicated in a plethora of biochemical interactions and
      biological functions, confounding attempts to coherently explain how their
      inactivation promotes carcinogenesis. Here, I argue that tumor suppression by
      BRCA1 and BRCA2 originates from their fundamental role in controlling the
      assembly and activity of macromolecular complexes that monitor chromosome
      duplication, maintenance, and segregation across the cell cycle. A tumor
      suppressive role for the BRCA proteins as "chromosome custodians" helps to
      explain the clinical features of cancer susceptibility after their inactivation,
      provides foundations for the rational therapy of BRCA-deficient cancers, and
      offers general insights into the mechanisms opposing early steps in human
      carcinogenesis. 

PMID- 24675955
TI  - Early childhood investments substantially boost adult health.
AB  - High-quality early childhood programs have been shown to have substantial
      benefits in reducing crime, raising earnings, and promoting education. Much less
      is known about their benefits for adult health. We report on the long-term health
      effects of one of the oldest and most heavily cited early childhood interventions
      with long-term follow-up evaluated by the method of randomization: the Carolina
      Abecedarian Project (ABC). Using recently collected biomedical data, we find that
      disadvantaged children randomly assigned to treatment have significantly lower
      prevalence of risk factors for cardiovascular and metabolic diseases in their mid
      30s. The evidence is especially strong for males. The mean systolic blood
      pressure among the control males is 143 millimeters of mercury (mm Hg), whereas
      it is only 126 mm Hg among the treated. One in four males in the control group is
      affected by metabolic syndrome, whereas none in the treatment group are affected.
      To reach these conclusions, we address several statistical challenges. We use
      exact permutation tests to account for small sample sizes and conduct a parallel
      bootstrap confidence interval analysis to confirm the permutation analysis. We
      adjust inference to account for the multiple hypotheses tested and for nonrandom
      attrition. Our evidence shows the potential of early life interventions for
      preventing disease and promoting health. 

PMID- 24675956
TI  - Structure of the yeast mitochondrial large ribosomal subunit.
AB  - Mitochondria have specialized ribosomes that have diverged from their bacterial
      and cytoplasmic counterparts. We have solved the structure of the yeast
      mitoribosomal large subunit using single-particle cryo-electron microscopy. The
      resolution of 3.2 angstroms enabled a nearly complete atomic model to be built de
      novo and refined, including 39 proteins, 13 of which are unique to mitochondria,
      as well as expansion segments of mitoribosomal RNA. The structure reveals a new
      exit tunnel path and architecture, unique elements of the E site, and a putative
      membrane docking site. 

PMID- 24675957
TI  - Observation of Brownian motion in liquids at short times: instantaneous velocity
      and memory loss.
AB  - Measurement of the instantaneous velocity of Brownian motion of suspended
      particles in liquid probes the microscopic foundations of statistical mechanics
      in soft condensed matter. However, instantaneous velocity has eluded experimental
      observation for more than a century since Einstein's prediction of the small
      length and time scales involved. We report shot-noise-limited, high-bandwidth
      measurements of Brownian motion of micrometer-sized beads suspended in water and
      acetone by an optical tweezer. We observe the hydrodynamic instantaneous velocity
      of Brownian motion in a liquid, which follows a modified energy equipartition
      theorem that accounts for the kinetic energy of the fluid displaced by the moving
      bead. We also observe an anticorrelated thermal force, which is conventionally
      assumed to be uncorrelated. 

PMID- 24675958
TI  - Quantum plasmon resonances controlled by molecular tunnel junctions.
AB  - Quantum tunneling between two plasmonic resonators links nonlinear quantum optics
      with terahertz nanoelectronics. We describe the direct observation of and control
      over quantum plasmon resonances at length scales in the range 0.4 to 1.3
      nanometers across molecular tunnel junctions made of two plasmonic resonators
      bridged by self-assembled monolayers (SAMs). The tunnel barrier width and height
      are controlled by the properties of the molecules. Using electron energy-loss
      spectroscopy, we directly observe a plasmon mode, the tunneling charge transfer
      plasmon, whose frequency (ranging from 140 to 245 terahertz) is dependent on the
      molecules bridging the gaps. 

PMID- 24675959
TI  - Optical broadband angular selectivity.
AB  - Light selection based purely on the angle of propagation is a long-standing
      scientific challenge. In angularly selective systems, however, the transmission
      of light usually also depends on the light frequency. We tailored the overlap of
      the band gaps of multiple one-dimensional photonic crystals, each with a
      different periodicity, in such a way as to preserve the characteristic Brewster
      modes across a broadband spectrum. We provide theory as well as an experimental
      realization with an all-visible spectrum, p-polarized angularly selective
      material system. Our method enables transparency throughout the visible spectrum
      at one angle--the generalized Brewster angle--and reflection at every other
      viewing angle.

PMID- 24675960
TI  - A non-cell autonomous role of E(z) to prevent germ cells from turning on a
      somatic cell marker.
AB  - In many metazoans, germ cells are separated from somatic lineages early in
      development and maintain their identity throughout life. Here, we show that a
      Polycomb group (PcG) component, Enhancer of Zeste [E(z)], a histone transferase
      that generates trimethylation at lysine 27 of histone H3, maintains germline
      identity in Drosophila adult testes. We find excessive early-stage somatic
      gonadal cells in E(z) mutant testes, which originate from both overproliferative
      cyst stem cells and germ cells turning on an early-stage somatic cell marker.
      Using complementary lineage-tracing experiments in E(z) mutant testes, a portion
      of excessive early-stage somatic gonadal cells are found to originate from early
      stage germ cells, including germline stem cells. Moreover, knocking down E(z)
      specifically in somatic cells caused this change, which suggests a non-cell
      autonomous role of E(z) to antagonize somatic identity in germ cells. 

PMID- 24675961
TI  - The Drosophila circadian clock is a variably coupled network of multiple
      peptidergic units.
AB  - Daily rhythms in behavior emerge from networks of neurons that express molecular
      clocks. Drosophila's clock neuron network consists of a diversity of cell types,
      yet is modeled as two hierarchically organized groups, one of which serves as a
      master pacemaker. Here, we establish that the fly's clock neuron network consists
      of multiple units of independent neuronal oscillators, each unified by its
      neuropeptide transmitter and mode of coupling to other units. Our work reveals
      that the circadian clock neuron network is not orchestrated by a small group of
      master pacemakers but rather consists of multiple independent oscillators, each
      of which drives rhythms in activity. 

PMID- 24675962
TI  - Quantifying global international migration flows.
AB  - Widely available data on the number of people living outside of their country of
      birth do not adequately capture contemporary intensities and patterns of global
      migration flows. We present data on bilateral flows between 196 countries from
      1990 through 2010 that provide a comprehensive view of international migration
      flows. Our data suggest a stable intensity of global 5-year migration flows at
      ~0.6% of world population since 1995. In addition, the results aid the
      interpretation of trends and patterns of migration flows to and from individual
      countries by placing them in a regional or global context. We estimate the
      largest movements to occur between South and West Asia, from Latin to North
      America, and within Africa. 

PMID- 24675963
TI  - Urine osmolarity and risk of dialysis initiation in a chronic kidney disease
      cohort--a possible titration target?
AB  - BACKGROUND: Increasing evidence is linking fluid intake, vasopressin suppression
      and osmotic control with chronic kidney disease progression. Interestingly, the
      association between urine volume, urine osmolarity and risk of dialysis
      initiation has not been studied in chronic kidney disease patients before.
      OBJECTIVE: To study the relationship between urine volume, urine osmolarity and
      the risk of initiating dialysis in chronic kidney disease. DESIGN: In a
      retrospective cohort analysis of 273 patients with chronic kidney disease stage 1
      4 we assessed the association between urine volume, urine osmolarity and the risk
      of dialysis by a multivariate proportional sub-distribution hazards model for
      competing risk data according to Fine and Gray. Co-variables were selected via
      the purposeful selection algorithm. RESULTS: Dialysis was reached in 105 patients
      over a median follow-up period of 92 months. After adjustment for age, baseline
      creatinine clearance, other risk factors and diuretics, a higher risk for
      initiation of dialysis was found in patients with higher urine osmolarity. The
      adjusted sub-distribution hazard ratio for initiation of dialysis was 2.04 (95%
      confidence interval, 1.06 to 3.92) for each doubling of urine osmolarity. After
      72 months, the estimated adjusted cumulative incidence probabilities of dialysis
      were 15%, 24%, and 34% in patients with a baseline urine osmolarity of 315, 510,
      and 775 mosm/L, respectively. CONCLUSIONS: We conclude that higher urine
      osmolarity is associated with a higher risk of initiating dialysis. As urine
      osmolarity is a potentially modifiable risk factor, it thus deserves further,
      prospective research as a potential target in chronic kidney disease progression.

PMID- 24675964
TI  - Mycobacterium ulcerans persistence at a village water source of Buruli ulcer
      patients.
AB  - Buruli ulcer (BU), a neglected tropical disease of the skin and subcutaneous
      tissue, is caused by Mycobacterium ulcerans and is the third most common
      mycobacterial disease after tuberculosis and leprosy. While there is a strong
      association of the occurrence of the disease with stagnant or slow flowing water
      bodies, the exact mode of transmission of BU is not clear. M. ulcerans has
      emerged from the environmental fish pathogen M. marinum by acquisition of a
      virulence plasmid encoding the enzymes required for the production of the
      cytotoxic macrolide toxin mycolactone, which is a key factor in the pathogenesis
      of BU. Comparative genomic studies have further shown extensive pseudogene
      formation and downsizing of the M. ulcerans genome, indicative for an adaptation
      to a more stable ecological niche. This has raised the question whether this
      pathogen is still present in water-associated environmental reservoirs. Here we
      show persistence of M. ulcerans specific DNA sequences over a period of more than
      two years at a water contact location of BU patients in an endemic village of
      Cameroon. At defined positions in a shallow water hole used by the villagers for
      washing and bathing, detritus remained consistently positive for M. ulcerans DNA.
      The observed mean real-time PCR Ct difference of 1.45 between the insertion
      sequences IS2606 and IS2404 indicated that lineage 3 M. ulcerans, which cause
      human disease, persisted in this environment after successful treatment of all
      local patients. Underwater decaying organic matter may therefore represent a
      reservoir of M. ulcerans for direct infection of skin lesions or vector
      associated transmission. 

PMID- 24675965
TI  - Internal jugular vein blood flow in multiple sclerosis patients and matched
      controls.
AB  - The aim of the study was to investigate the Internal Jugular Veins dynamics using
      contrast enhanced ultrasonography in Multiple Sclerosis patients, clinically
      isolated syndrome patients and healthy controls. Contrast enhanced
      ultrasonography imaging of the Internal Jugular Vein was performed in fifty-eight
      patients with Multiple Sclerosis, seven clinically isolated syndrome patients and
      in thirteen healthy controls. Time-intensity curves were quantified using a semi
      automated method and compared with clinical disease outcomes. Wash-out parameters
      were calculated and six Time-intensity curves shapes were created. Significantly
      reduction of wash-out rate in Internal Jugular Veins was detected in Multiple
      Sclerosis patients compared to healthy controls [22.2% (2.7%-65.9%) vs. 33.4%
      (16.2%-76.8%); P<0.005]. Internal Jugular Vein enhancement was heterogeneous in
      patients with Multiple Sclerosis and consisted of slow wash-out Time-intensity
      curves shapes, compared with almost only one type of Time-intensity curves shape
      in control subjects that correspond to fast enhancement and fast wash-out. The
      vein wash-in parameters were similar in Multiple Sclerosis group compared with
      controls. A significant correlation was found between Internal Jugular Vein wash
      out and level of disability (R =  -0.402, p<0.05). Contrast enhanced
      ultrasonography of the Internal Jugular Vein with time intensity curve analysis
      revealed alterations of cerebral venous outflow in Multiple Sclerosis patients,
      however mechanisms that determine this condition remains unclear.

PMID- 24675966
TI  - Covalent and density-controlled surface immobilization of E-cadherin for adhesion
      force spectroscopy.
AB  - E-cadherin is a key cell-cell adhesion molecule but the impact of receptor
      density and the precise contribution of individual cadherin ectodomains in
      promoting cell adhesion are only incompletely understood. Investigating these
      mechanisms would benefit from artificial adhesion substrates carrying different
      cadherin ectodomains at defined surface density. We therefore developed a
      quantitative E-cadherin surface immobilization protocol based on the SNAP-tag
      technique. Extracellular (EC) fragments of E-cadherin fused to the SNAP-tag were
      covalently bound to self-assembled monolayers (SAM) of thiols carrying
      benzylguanine (BG) head groups. The adhesive functionality of the different E
      cadherin surfaces was then assessed using cell spreading assays and single-cell
      (SCSF) and single-molecule (SMSF) force spectroscopy. We demonstrate that an E
      cadherin construct containing only the first and second outmost EC domain (E1-2)
      is not sufficient for mediating cell adhesion and yields only low single cadherin
      cadherin adhesion forces. In contrast, a construct containing all five EC domains
      (E1-5) efficiently promotes cell spreading and generates strong single cadherin
      and cell adhesion forces. By varying the concentration of BG head groups within
      the SAM we determined a lateral distance of 5-11 nm for optimal E-cadherin
      functionality. Integrating the results from SCMS and SMSF experiments furthermore
      demonstrated that the dissolution of E-cadherin adhesion contacts involves a
      sequential unbinding of individual cadherin receptors rather than the sudden
      rupture of larger cadherin receptor clusters. Our method of covalent, oriented
      and density-controlled E-cadherin immobilization thus provides a novel and
      versatile platform to study molecular mechanisms underlying cadherin-mediated
      cell adhesion under defined experimental conditions. 

PMID- 24675967
TI  - The need to nurse the nurse: emotional labor in neonatal intensive care.
AB  - In this 14-month ethnographic study, I examined the emotional labor and coping
      strategies of 114, level-4, neonatal intensive care unit (NICU) nurses. Emotional
      labor was an underrecognized component in the care of vulnerable infants and
      families. The nature of this labor was contextualized within complex personal,
      professional, and organizational layers of demand on the emotions of NICU nurses.
      Coping strategies included talking with the sisterhood of nurses, being a super
      nurse, using social talk and humor, taking breaks, offering flexible aid,
      withdrawing from emotional pain, transferring out of the NICU, attending memorial
      services, and reframing loss to find meaning in work. The organization had strong
      staffing, but emotional labor was not recognized, supported, or rewarded. The
      findings can contribute to the development of interventions to nurse the nurse,
      and to ultimately facilitate NICU nurses' nurturance of stressed families. These
      have implications for staff retention, job satisfaction, and delivery of care. 

PMID- 24675968
TI  - Cross-family translational genomics of abiotic stress-responsive genes between
      Arabidopsis and Medicago truncatula.
AB  - Cross-species translation of genomic information may play a pivotal role in
      applying biological knowledge gained from relatively simple model system to other
      less studied, but related, genomes. The information of abiotic stress (ABS)
      responsive genes in Arabidopsis was identified and translated into the legume
      model system, Medicago truncatula. Various data resources, such as TAIR/AtGI DB,
      expression profiles and literatures, were used to build a genome-wide list of ABS
      genes. tBlastX/BlastP similarity search tools and manual inspection of alignments
      were used to identify orthologous genes between the two genomes. A total of 1,377
      genes were finally collected and classified into 18 functional criteria of gene
      ontology (GO). The data analysis according to the expression cues showed that
      there was substantial level of interaction among three major types (i.e.,
      drought, salinity and cold stress) of abiotic stresses. In an attempt to
      translate the ABS genes between these two species, genomic locations for each
      gene were mapped using an in-house-developed comparative analysis platform. The
      comparative analysis revealed that fragmental colinearity, represented by only 37
      synteny blocks, existed between Arabidopsis and M. truncatula. Based on the
      combination of E-value and alignment remarks, estimated translation rate was
      60.2% for this cross-family translation. As a prelude of the functional
      comparative genomic approaches, in-silico gene network/interactome analyses were
      conducted to predict key components in the ABS responses, and one of the sub
      networks was integrated with corresponding comparative map. The results
      demonstrated that core members of the sub-network were well aligned with
      previously reported ABS regulatory networks. Taken together, the results indicate
      that network-based integrative approaches of comparative and functional genomics
      are important to interpret and translate genomic information for complex traits
      such as abiotic stresses. 

PMID- 24675969
TI  - Landscape heterogeneity-biodiversity relationship: effect of range size.
AB  - The importance of landscape heterogeneity to biodiversity may depend on the size
      of the geographic range of species, which in turn can reflect species traits
      (such as habitat generalization) and the effects of historical and contemporary
      land covers. We used nationwide bird survey data from Japan, where heterogeneous
      landscapes predominate, to test the hypothesis that wide-ranging species are
      positively associated with landscape heterogeneity in terms of species richness
      and abundance, whereas narrow-ranging species are positively associated with
      landscape homogeneity in the form of either open or forest habitats. We used
      simultaneous autoregressive models to explore the effects of climate,
      evapotranspiration, and landscape heterogeneity on the richness and abundance of
      breeding land-bird species. The richness of wide-ranging species and the total
      species richness were highest in heterogeneous landscapes, where many wide
      ranging species showed the highest abundance. In contrast, the richness of narrow
      ranging species was not highest in heterogeneous landscapes; most of those
      species were abundant in either open or forest landscapes. Moreover, in open
      landscapes, narrow-ranging species increased their species richness with
      decreasing temperature. These results indicate that heterogeneous landscapes are
      associated with rich bird diversity but that most narrow-ranging species prefer
      homogeneous landscapes--particularly open habitats in colder regions, where
      grasslands have historically predominated. There is a need to reassess the
      generality of the heterogeneity-biodiversity relationship, with attention to the
      characteristics of species assemblages determined by environments at large
      spatiotemporal scales.

PMID- 24675971
TI  - Interaction of extrinsic chemical factors affecting photodegradation of dissolved
      organic matter in aquatic ecosystems.
AB  - Photochemical degradation of dissolved organic matter (DOM) plays an important
      role in the carbon cycle. Irradiation experiments were conducted to evaluate the
      influence of chemical factors, specifically those expected to be altered in
      natural waters by atmospheric acid deposition, on photodegradation of DOM. These
      included pH, nitrate, iron and calcium. The experiments were carried out using
      stream and lake water samples with a wide range of dissolved organic carbon (DOC)
      concentration. Decreasing DOC concentration along with decreasing absorbance was
      observed during three-week exposures to natural solar radiation as well as during
      laboratory experiments with artificial solar radiation. The pH of the samples
      significantly affected degradation rates of DOM especially with elevated iron,
      while no influence of nitrate or calcium concentration was observed. Addition of
      Fe(III) did not significantly affect photodegradation and photobleaching rate
      constants in samples at circumneutral pH. Acid pH increased photodegradation
      rates. The results suggest that photodegradation rates of DOM will decrease
      during recovery from acidification. Hence, lower photodegradation rates may be
      responsible for increases in DOM observed in some regions of North America and
      Europe. 

PMID- 24675970
TI  - Detection of human papillomavirus infection and p16 immunohistochemistry
      expression in bladder cancer with squamous differentiation.
AB  - OBJECTIVES: To determine the potential association between HPV infection and the
      squamous cell component of urothelial carcinoma (UC) of the bladder and to
      validate p16 overexpression as a surrogate marker for HPV infection in these
      cancers among Koreans. METHODS: We analyzed the presence of HPV infection using
      an HPV-DNA chip and the expression of p16 using immunohistochemistry in 47
      subjects between July 2001 and March 2011. The study group (n = 35) included
      patients with squamous differentiation of UC of the bladder. The control group (n
      = 12) included patients with squamous metaplasia of the bladder. RESULTS:
      Baseline characteristics of control and study groups were similar. HPV DNA
      detection rates were approximately 2-fold higher in the study than the control
      group (17.1% [6/35] versus 8.3% [1/12], respectively), but the difference was not
      statistically significant. P16 overexpression was detected in 16/35 (45.7%) study
      group and 1/12 (8.3%) control group samples (p = 0.034). Both HPV-positivity and
      p16 overexpression were present in 3/35 (8.8%) study group samples, but none of
      the control group (p = 0.295). In the study group, the percentage of HPV-positive
      cases who were non-smokers was 2-fold higher than the percentage of HPV-negative
      cases who were non-smokers (66.7% [4/6] versus 31.0% [9/29], respectively);
      however, statistical significance was not achieved due to the small sample size.
      CONCLUSIONS: HPV infection may be associated with UC of the bladder with squamous
      differentiation, especially in non-smokers. However, p16 expression does not
      appear to be a strong surrogate marker for evidence of HPV infection in this type
      of cancer.

PMID- 24675972
TI  - Tunable water desalination across graphene oxide framework membranes.
AB  - The performance of graphene oxide framework (GOF) membranes for water
      desalination is assessed using classical molecular dynamics (MD) simulations. The
      coupling between water permeability and salt rejection of GOF membranes is
      studied as a function of linker concentration n, thickness h and applied pressure
      DeltaP. The simulations reveal that water permeability in GOF-(n,h) membranes can
      be tuned from ~5 (n = 32 and h = 6.5 nm) to 400 L cm(-2) day(-1) MPa(-1) (n = 64
      and h = 2.5 nm) and follows a Cnh(-alphan) law. For a given pore size (n = 16 or
      32), water permeability of GOF membranes increases when the pore spacing
      decreases, whereas for a given pore spacing (n = 32 or 64), water permeability
      increases by up to two orders of magnitude when the pore size increases.
      Furthermore, for linker concentrations n <= 32, the high water permeability
      corresponds to a 100% salt rejection, elevating this type of GOF membrane as an
      ideal candidate for water desalination. Compared to experimental performance of
      reverse osmosis membranes, our calculations suggest that under the same
      conditions of applied pressure and characteristics of membranes (DeltaP ~ 10 MPa
      and h ~ 100 nm), one can expect a perfect salt rejection coupled to a water
      permeability two orders of magnitude higher than existing technologies, i.e.,
      from a few cL cm(-2) day(-1) MPa(-1) to a few L cm(-2) day(-1) MPa(-1). 

PMID- 24675974
TI  - Fatigue degradation and electric recovery in Silicon solar cells embedded in
      photovoltaic modules.
AB  - Cracking in Silicon solar cells is an important factor for the electrical power
      loss of photovoltaic modules. Simple geometrical criteria identifying the amount
      of inactive cell areas depending on the position of cracks with respect to the
      main electric conductors have been proposed in the literature to predict worst
      case scenarios. Here we present an experimental study based on the
      electroluminescence (EL) technique showing that crack propagation in
      monocrystalline Silicon cells embedded in photovoltaic (PV) modules is a much
      more complex phenomenon. In spite of the very brittle nature of Silicon, due to
      the action of the encapsulating polymer and residual thermo-elastic stresses,
      cracked regions can recover the electric conductivity during mechanical unloading
      due to crack closure. During cyclic bending, fatigue degradation is reported.
      This pinpoints the importance of reducing cyclic stresses caused by vibrations
      due to transportation and use, in order to limit the effect of cracking in
      Silicon cells. 

PMID- 24675975
TI  - Thermodynamic and kinetic analysis of heterogeneous photocatalysis for
      semiconductor systems.
AB  - Since the report of the Honda-Fujishima effect, heterogeneous photocatalysis has
      attracted much attention around the world because of its potential energy and
      environmental applications. Although great progresses have been made in recent
      years, most were focused on preparing highly-active photocatalysts and
      investigating visible light utilization. In fact, we are still unclear on the
      thermodynamic and kinetic nature of photocatalysis to date, which sometimes leads
      to misunderstandings for experimental results. It is timely to give a review and
      discussion on the thermodynamics and kinetics of photocatalysis, so as to direct
      future researches. However, there is an absence of a detailed review on this
      topic until now. In this article, we tried to review and discuss the
      thermodynamics and kinetics of photocatalysis. We explained the thermodynamic
      driving force of photocatalysis, and distinguished the functions of light and
      heat in photocatalysis. The Langmuir-Hinshelwood kinetic model, the OH oxidation
      mechanism, and the direct-indirect (D-I) kinetic model were reviewed and
      compared. Some applications of the D-I model to study photocatalytic kinetics
      were also discussed. The electron transport mode and its importance in
      photocatalysis were investigated. Finally, the intrinsic relation between the
      kinetics and the thermodynamics of photocatalytic reactions was discussed. 

PMID- 24675973
TI  - A discrete model of Drosophila eggshell patterning reveals cell-autonomous and
      juxtacrine effects.
AB  - The Drosophila eggshell constitutes a remarkable system for the study of
      epithelial patterning, both experimentally and through computational modeling.
      Dorsal eggshell appendages arise from specific regions in the anterior follicular
      epithelium that covers the oocyte: two groups of cells expressing broad (roof
      cells) bordered by rhomboid expressing cells (floor cells). Despite the large
      number of genes known to participate in defining these domains and the important
      modeling efforts put into this developmental system, key patterning events still
      lack a proper mechanistic understanding and/or genetic basis, and the literature
      appears to conflict on some crucial points. We tackle these issues with an
      original, discrete framework that considers single-cell models that are
      integrated to construct epithelial models. We first build a phenomenological
      model that reproduces wild type follicular epithelial patterns, confirming EGF
      and BMP signaling input as sufficient to establish the major features of this
      patterning system within the anterior domain. Importantly, this simple model
      predicts an instructive juxtacrine signal linking the roof and floor domains. To
      explore this prediction, we define a mechanistic model that integrates the
      combined effects of cellular genetic networks, cell communication and network
      adjustment through developmental events. Moreover, we focus on the anterior
      competence region, and postulate that early BMP signaling participates with early
      EGF signaling in its specification. This model accurately simulates wild type
      pattern formation and is able to reproduce, with unprecedented level of precision
      and completeness, various published gain-of-function and loss-of-function
      experiments, including perturbations of the BMP pathway previously seen as
      conflicting results. The result is a coherent model built upon rules that may be
      generalized to other epithelia and developmental systems. 

PMID- 24675976
TI  - [Amniotic fluid volume and maternal outcomes in women with preterm premature
      rupture of membranes].
AB  - PURPOSE: To describe the potential influence of amniotic fluid on the maternal
      outcome of preterm premature rupture of membranes (PROM). METHODS: An
      observational, retrospective cohort study was conducted between December 2012 and
      January 2008 on 86 pregnant women with preterm PROM and a gestational age (GA) of
      24 to 35 weeks. The amniotic fluid index (AFI) was used to measure aminiotic
      fluid volume. Pregnant women were compared at two cut-off points: those with AFI
      <5.0 and >=5.0 cm and AFI <3.0 and >=3.0 cm. We excluded women with hypertensive
      disorders, diabetes mellitus, fetal malformations and a diagnosis of infections
      at admission. For statistical analysis, we used the chi2 test or Fisher's exact
      test, when appropriate, and simple linear regression analysis, with the level of
      significance set at 5%. We calculated the Risk Ratio (RR) and its 95% confidence
      interval (95%CI). RESULTS: When maternal outcomes were assessed by comparing ILA
      >=5.0 versus <5.0 cm, no significant differences were detected. However, when
      considering ILA <3.0 and >=3.0 cm, there was an increased risk of
      chorioamnionitis (36.7 versus10.7%, RR: 3.4, 95%CI 1.4 -8.3, p=0.004), with no
      significant differences for the other variables. There was also a statistically
      significant positive correlation between AFI and gestational age at delivery
      (R2=0.78, p<0.0001). CONCLUSIONS: AFI <3.0 cm causes a three-fold increase in the
      risk for chorioamnionitis; also, the higher the ILA, the higher the gestational
      age at delivery.

PMID- 24675977
TI  - Cardiovascular risk in middle-aged breast cancer survivors: a comparison between
      two risk models.
AB  - PURPOSE: It was to assess the risk of cardiovascular disease (CVD) in breast
      cancer survivors (BCS). METHODS: This cross-sectional study analyzed 67 BCS, aged
      45 -65 years, who underwent complete oncological treatment, but had not received
      hormone therapy, tamoxifen or aromatase inhibitors during the previous 6 months.
      Lipid profile and CVD risk were evaluated, the latter using the Framingham and
      Systematic COronary Risk Evaluation (SCORE) models. The agreement between
      cardiovascular risk models was analyzed by calculating a kappa coefficient and
      its 95% confidence interval (CI). RESULTS: Mean subject age was 53.2+/-6.0 years,
      with rates of obesity, hypertension, and dyslipidemia of 25, 34 and 90%,
      respectively. The most frequent lipid abnormalities were high total cholesterol
      (70%), high LDL-C (51%) and high non-HDL-C (48%) concentrations. Based on the
      Framingham score, 22% of the participants had a high risk for coronary artery
      disease. According to the SCORE model, 100 and 93% of the participants were at
      low risk for fatal CVD in populations at low and high risk, respectively, for
      CVD. The agreement between the Framingham and SCORE risk models was poor (kappa:
      0.1; 95%CI 0.01 -0.2) for populations at high risk for CVD. CONCLUSIONS: These
      findings indicate the need to include lipid profile and CVD risk assessment in
      the follow-up of BCS, focusing on adequate control of serum lipid concentrations.

PMID- 24675978
TI  - [Hysteroscopic appearance of the endometrial cavity after endometrial ablation].
AB  - PURPOSE: To examine the aspect of the uterine cavity after hysteroscopic
      endometrial ablation, to determine the prevalence of synechiae after the
      procedure, and to analyze the importance of hysteroscopy during the postoperative
      period. METHODS: The results of the hysteroscopic exams of 153 patients who
      underwent outpatient hysteroscopy after endometrial ablation due to abnormal
      uterine bleeding of benign etiology during the period from January 2006 to July
      2011 were retrospectively reviewed. The patients were divided into two groups:
      HIST<=60 (n=90) consisting of patients undergoing the exam 40-60 days after the
      ablation procedure, and the group HIST>60 (n=63) consisting of patients
      undergoing the exam between 61 days and 12 months after the procedure. RESULTS:
      In the HIST<=60 group, 30% of the patients presented some degree of synechiae:
      synechiae grade I in 4.4% of patients, grade II in 6.7% , grade IIa in 4.4%,
      grade III in 7.8%, and grade IV in 2.2%. In the HIST>60 group, 53.9% of all cases
      had synechiae, 3.2% were grade I, 11.1% grade II, 7.9% grade IIa, 15.9% grade
      III, and 4.8% grade IV. Hematometra was detected in 2.2 % of all cases in group
      HIST<=60 and in 6.3% of all cases in group HIST>60. CONCLUSIONS: The uterine
      cavity of the patients submitted to diagnostic hysteroscopy up to 60 days after
      endometrial ablation showed significantly fewer synechiae compared to the uterine
      cavity of patients who underwent the exam after 60 days. Long-term follow-up is
      necessary to fully evaluate the importance of outpatient hysteroscopy after
      endometrial ablation regarding menstrual patterns, risk of cancer and prevalence
      of treatment failure.

PMID- 24675979
TI  - Co-delivery of doxorubicin and SATB1 shRNA by thermosensitive magnetic cationic
      liposomes for gastric cancer therapy.
AB  - In previous a study, we had developed a novel thermosensitive magnetic delivery
      system based on liposomes. This study aimed to evaluate the efficiency of this
      system for the co-delivery of both drugs and genes to the same cell and its anti
      tumor effects on gastric cancer. Doxorubicin (DOX) and SATB1 shRNA vector were
      loaded into the co-delivery system, and in vitro DOX thermosensitive release
      activity, targeted gene silencing efficiency, targeted cellular uptake, in vitro
      cytotoxicity, as well as in vivo anti-tumor activity were determined. The results
      showed that this co-delivery system had desirable targeted delivery efficacy, DOX
      thermosensitive release and SATB1 gene silencing. Moreover, the co-delivery of
      DOX and SATB1 shRNA exhibited enhanced activity to inhibit gastric cancer cell
      growth in vitro and in vivo, compared to single delivery. In conclusion, the
      novel thermosensitive magnetic drug and gene co-delivery system has promising
      application in combined chemotherapy and gene therapy for gastric cancer. 

PMID- 24675980
TI  - A microfluidic tubing method and its application for controlled synthesis of
      polymeric nanoparticles.
AB  - This report describes a straightforward but robust tubing method for connecting
      polydimethylsiloxane (PDMS) microfluidic devices to external equipment. The
      interconnection is irreversible and can sustain a pressure of up to 4.5 MPa that
      is characterized experimentally and theoretically. To demonstrate applications of
      this high-pressure tubing technique, we fabricate a semicircular microfluidic
      channel to implement a high-throughput, size-controlled synthesis of poly(lactic
      co-glycolic acid) (PLGA) nanoparticles ranging from 55 to 135 nm in diameter.
      This microfluidic device allows for a total flow rate of 410 mL h(-1), resulting
      in enhanced convective mixing which can be utilized to precipitate small size
      nanoparticles with a good dispersion. We expect that this tubing technique would
      be widely used in microfluidic chips for nanoparticle synthesis, cell
      manipulation, and potentially nanofluidic applications. 

PMID- 24675981
TI  - Selection of orphan Rhs toxin expression in evolved Salmonella enterica serovar
      Typhimurium.
AB  - Clonally derived bacterial populations exhibit significant genotypic and
      phenotypic diversity that contribute to fitness in rapidly changing environments.
      Here, we show that serial passage of Salmonella enterica serovar Typhimurium LT2
      (StLT2) in broth, or within a mouse host, results in selection of an evolved
      population that inhibits the growth of ancestral cells by direct contact. Cells
      within each evolved population gain the ability to express and deploy a cryptic
      "orphan" toxin encoded within the rearrangement hotspot (rhs) locus. The Rhs
      orphan toxin is encoded by a gene fragment located downstream of the "main" rhs
      gene in the ancestral strain StLT2. The Rhs orphan coding sequence is linked to
      an immunity gene, which encodes an immunity protein that specifically blocks Rhs
      orphan toxin activity. Expression of the Rhs orphan immunity protein protects
      ancestral cells from the evolved lineages, indicating that orphan toxin activity
      is responsible for the observed growth inhibition. Because the Rhs orphan toxin
      is encoded by a fragmented reading frame, it lacks translation initiation and
      protein export signals. We provide evidence that evolved cells undergo
      recombination between the main rhs gene and the rhs orphan toxin gene fragment,
      yielding a fusion that enables expression and delivery of the orphan toxin. In
      this manner, rhs locus rearrangement provides a selective advantage to a
      subpopulation of cells. These observations suggest that rhs genes play important
      roles in intra-species competition and bacterial evolution. 

PMID- 24675982
TI  - Influenza-like illnesses in Senegal: not only focus on influenza viruses.
AB  - Influenza surveillance in African countries was initially restricted to the
      identification of circulating strains. In Senegal, the network has recently been
      enhanced (i) to include epidemiological data from Dakar and other regions and
      (ii) to extend virological surveillance to other respiratory viruses.
      Epidemiological data from the sentinel sites is transmitted daily by mobile
      phone. The data include those for other febrile syndromes similar to influenza
      like illnesses (ILI), corresponding to integrated approach. Also, clinical
      samples are randomly selected and analyzed for influenza and other respiratory
      viruses. There were 101,640 declared visits to the 11 sentinel sites between week
      11-2012 and week 35-2013; 22% of the visits were for fever syndromes and 23% of
      the cases of fever syndrome were ILI. Influenza viruses were the second most
      frequent cause of ILI (20%), after adenoviruses (21%) and before rhinoviruses
      (18%) and enteroviruses (15%). Co-circulation and co-infection were frequent and
      were responsible for ILI peaks. The first months of implementation of the
      enhanced surveillance system confirmed that viruses other the influenza make
      large contributions to influenza-like illnesses. It is therefore important to
      consider these etiologies in the development of strategies to reduce respiratory
      infections. More informative tools and research studies are required to assess
      the burden of respiratory infections in developing countries. 

PMID- 24675985
TI  - Community-based active tuberculosis case finding in poor urban settlements of
      Phnom Penh, Cambodia: a feasible and effective strategy.
AB  - BACKGROUND: In light of the limitations of the current case finding strategies
      and the global urgency to improve tuberculosis (TB) case-detection, a renewed
      interest in active case finding (ACF) has risen. The WHO calls for more evidence
      on innovative ways of TB screening, especially from low-income countries, to
      inform global guideline development. We aimed to assess the feasibility of
      community-based ACF for TB among the urban poor in Cambodia and determine its
      impact on case detection, treatment uptake and outcome. METHODS: Between 9/2/2012
      31/3/2013 the Sihanouk Hospital Center of HOPE conducted a door-to-door survey
      for TB in deprived communities of Phnom Penh. TB workers and community health
      volunteers performed symptom screening, collected sputum and facilitated specimen
      transport to the laboratories. Fluorescence microscopy was introduced at three
      referral hospitals. The GeneXpert MTB/RIF assay (Xpert) was performed at tertiary
      level for individuals at increased risk of HIV-associated, drug-resistant or
      smear-negative TB. Mobile phone/short message system (SMS) was used for same-day
      issuing of positive results. TB workers contacted diagnosed patients and referred
      them for care at their local health centre. RESULTS: In 14 months, we screened
      315.874 individuals; we identified 12.201 aged >= 15 years with symptoms
      suggestive of TB; 84% provided sputum. We diagnosed 783, including 737
      bacteriologically confirmed, TB cases. Xpert testing yielded 41% and 48%
      additional diagnoses among presumptive HIV-associated and multidrug-resistant TB
      cases, respectively. The median time from sputum collection to notification (by
      SMS) of the first positive (microscopy or Xpert) result was 3 days (IQR 2-6).
      Over 94% commenced TB treatment and 81% successfully completed it. CONCLUSION:
      Our findings suggest that among the urban poor ACF for TB, using a sensitive
      symptom screen followed by smear-microscopy and targeted Xpert, contributed to
      improved case detection of drug-susceptible and drug-resistant TB, shortening the
      diagnostic delay, and successfully bringing patients into care.

PMID- 24675987
TI  - Peripheral blood telomere content is greater in patients with endometriosis than
      in controls.
AB  - The etiology of endometriosis remains poorly understood but circulating stem
      cells may contribute. Telomeres shorten with cell divisions and age. Stem cells
      attempt to compensate for telomere attrition through the action of telomerase.
      Since circulating stem cells may contribute to endometriosis, we compared
      telomere content in lymphocytes of patients with and without endometriosis.
      METHODS: Observational study comparing peripheral lymphocytes telomere content,
      measured by quantitative polymerase chain reaction, in patients with (n = 86) and
      without endometriosis (n = 21). FINDINGS: Patients with endometriosis had longer
      telomeres than that of matched, endometriosis-free controls (telomere to single
      copy gene ratio [T/S ratio] of 1.62 vs 1.34, respectively, P = .00002). Patients
      with endometriosis were 8.1-fold more likely to have long telomeres. (odds ratio
      = 8.1, 95% confidence interval: 1.28-51.57, P = .0264). INTERPRETATION: Longer
      telomeres could be consistent with a stem cell origin of endometriosis.

PMID- 24675986
TI  - Heterogeneity and breadth of host antibody response to KSHV infection
      demonstrated by systematic analysis of the KSHV proteome.
AB  - The Kaposi sarcoma associated herpesvirus (KSHV) genome encodes more than 85 open
      reading frames (ORFs). Serological evaluation of KSHV infection now generally
      relies on reactivity to just one latent and/or one lytic protein (commonly ORF73
      and K8.1). Most of the other polypeptides encoded by the virus have unknown
      antigenic profiles. We have systematically expressed and purified products from
      72 KSHV ORFs in recombinant systems and analyzed seroreactivity in US patients
      with KSHV-associated malignancies, and US blood donors (low KSHV seroprevalence
      population). We identified several KSHV proteins (ORF38, ORF61, ORF59 and K5)
      that elicited significant responses in individuals with KSHV-associated diseases.
      In these patients, patterns of reactivity were heterogeneous; however, HIV
      infection appeared to be associated with breadth and intensity of serological
      responses. Improved antigenic characterization of additional ORFs may increase
      the sensitivity of serologic assays, lead to more rapid progresses in
      understanding immune responses to KSHV, and allow for better comprehension of the
      natural history of KSHV infection. To this end, we have developed a bead-based
      multiplex assay detecting antibodies to six KSHV antigens. 

PMID- 24675988
TI  - L-arginine catabolism is driven mainly towards nitric oxide synthesis in the
      erythrocytes of patients with type 2 diabetes at first clinical onset.
AB  - BACKGROUND: We investigated the l-arginine (l-Arg)-nitric oxide (NO) metabolic
      pathway in the erythrocytes (RBCs) and plasma of subjects with type 2 diabetes at
      first clinical onset. METHODS: RBCs and plasma were collected from 26 patients
      with type 2 diabetes at first clinical onset and 19 age-matched non-diabetes
      subjects as controls. l-Arg content was assayed by capillary electrophoresis. We
      measured arginase activity and nitrate/nitrite concentrations by
      spectrophotometry, and glycosylated haemoglobin (HbA1c) by standardized
      immunoturbidimetry. RESULTS: We found that, when compared with controls, l-Arg
      content was similar in RBCs while decreased in the plasma of patients with type 2
      diabetes. Interestingly, arginase activity was lower in RBCs and increased in
      plasma of patients with diabetes. NO production was higher in RBCs in patients
      with type 2 diabetes, while no difference was found in the plasma of our
      subjects. CONCLUSIONS: l-Arg catabolism is driven mainly towards NO synthesis in
      RBCs of patients with type 2 diabetes at first clinical onset. The decreased RBC
      arginase activity could be considered a potential mechanism of increased RBC NO
      production in early diabetes. Therefore, the RBC pool would represent a
      potentially compensatory intravascular compartment for endothelial dysfunction in
      diabetes.

PMID- 24675989
TI  - A revised method for determination of serum mercaptalbumin and non-mercaptalbumin
      by high-performance liquid chromatography coupled with postcolumn bromocresol
      green reaction.
AB  - BACKGROUND: Previously, high-performance liquid chromatography (HPLC) equipped
      with ultraviolet or fluorescence detectors has been used for separation of human
      mercaptalbumin (HMA) and human non-mercaptalbumin (HNA). However, it is difficult
      to perform reliable chromatographic analysis due to peak interference of such
      serum compounds as uric acid and bilirubin. The aim of this study is to explore a
      selective and simple analytical method for the determination of HMA and HNA.
      METHOD: HMA and HNA in serum sample were separated by HPLC and reacted with
      bromocresol green using a postcolumn reaction scheme. RESULTS: A complete
      separation of HMA and HNA is achieved in less than 30 min by using weak anion
      exchange columns and isocratic elution. Within-run and between-day precisions at
      albumin concentration of 45 g/L were 4.2 and 1.7% for HMA and 4.5 and 4.6% for
      HNA, respectively. There was no interference in HMA and HNA peaks when bilirubin
      , haemoglobin- or chyle-spiked pooled serum samples were analysed. CONCLUSION:
      Our method is reliable and not labour-intensive and, therefore, might be
      applicable for clinical and epidemiological studies.

PMID- 24675990
TI  - Could nitazoxanide be added to other essential medicines for integrated neglected
      tropical disease control and elimination?

PMID- 24675991
TI  - How does conformational flexibility influence key structural features involved in
      activation of anaplastic lymphoma kinase?
AB  - Anaplastic Lymphoma Kinase (ALK) plays a major role in developing tumor processes
      and therefore has emerged as a validated therapeutic target. Applying atomistic
      molecular dynamics simulations on the wild type enzyme and the nine most
      frequently occurring and clinically important activation mutants we revealed
      important conformational effects on key interactions responsible for the
      activation of the enzyme. 

PMID- 24675992
TI  - A colloidal water-stable MOF as a broad-range fluorescent pH sensor via post
      synthetic modification.
AB  - We report for the first time the pH-dependent fluorescence of UiO-66-NH2 across
      the wide range from 1 to 9. By application of a post-synthetic modification (PSM)
      diazotisation strategy, we synthesized a new material, UiO-66-N=N-ind, which
      shows increased chemical stability and enhanced sensing up to pH 12.

PMID- 24675993
TI  - Ethanol lock therapy (E-Lock) in the prevention of catheter-related bloodstream
      infections (CR-BSI) after major heart surgery (MHS): a randomized clinical trial.
AB  - BACKGROUND: Lock-therapy with antimicrobials has been used for the treatment and
      prevention of catheter-related bloodstream infections (CR-BSI). Experiences with
      Ethanol-Locks (E-locks) have included therapeutic interventions with variable
      results. Patients undergoing Major Heart Surgery (MHS) are a high-risk population
      for CR-BSI.The aim of this study was to assess the efficacy and tolerance to E
      Locks in the prevention of CR-BSI of patients undergoing MHS. METHODS AND
      FINDINGS: This is an academic, prospective, randomized, non-blinded and
      controlled clinical trial assessing the incidence of CR-BSI of patients with E
      locks (E-lock) and the tolerance to the procedure in comparison with patients
      receiving conventional catheter-care (CCC). Patients undergoing MHS with
      intravascular catheters for more than 48 hours were randomly assigned into
      treatment or control group by a computer-generated list of randomly assigned
      numbers. In the treatment group, all their catheter lumens were locked with an
      ethanol solution at 70% for two hours, every three days (E-Locks). The control
      group received conventional catheter-care (CCC). Overall, 200 patients with 323
      catheters were included in the study, which was stopped after 10 months due to
      adverse events. Of them, 179 catheters (113 patients) had E-Locks and 144
      catheters (87 patients) were CCC. Euroscore Surgical Risk in both groups was 4.04
      vs 4.07 p = 0.94 respectively. The results for the E-Locks and CCC were as
      follows: Incidence of CR-BSI/1000 days of exposure 2.1 vs 5.2 (p = 0.33),
      catheter tip colonization 14 (7.8%) vs 6 (4.2%) patients (p = 0.17), median
      length of hospital stay, 15 vs 16 days (p = 0.77). Seven patients (6.19%), all in
      the ethanol branch, had to discontinue the trial due to intolerance or adverse
      events. CONCLUSIONS: We do not recommend prophylaxis of CR-BSI with ethanol-lock
      on a routine basis in patients undergoing Major Heart Surgery. TRIAL
      REGISTRATION: Clinical Trials.gov NCT01229592.

PMID- 24675994
TI  - Emulsions stabilised by whey protein microgel particles: towards food-grade
      Pickering emulsions.
AB  - We have investigated a new class of food-grade particles, whey protein microgels,
      as stabilisers of triglyceride-water emulsions. The sub-micron particles
      stabilized oil-in-water emulsions at all pH with and without salt. All emulsions
      creamed but exhibited exceptional resistance to coalescence. Clear correlations
      exist between the properties of the microgels in aqueous dispersion and the
      resulting emulsion characteristics. For conditions in which the particles were
      uncharged, fluid emulsions with relatively large drops were stabilised, whereas
      emulsions stabilized by charged particles contained smaller flocculated drops. A
      combination of optical microscopy of the drops and spectrophotometry of the
      resolved aqueous phase allowed us to estimate the interfacial adsorption
      densities of the particles using the phenomenon of limited coalescence. We deduce
      two classes of particle arrangement. Complete adsorption of the particles was
      obtained when they were neutral or when their charges were screened by salt
      resulting in at least one particle monolayer at the interface. By contrast, only
      around 50% of the particles adsorbed when they were charged with emulsion drops
      being covered by less than half a monolayer. These findings were supported by
      direct visualization of drop interfaces using cryo-scanning electron microscopy.
      Uncharged particles were highly aggregated and formed a continuous 2-D network at
      the interface. Otherwise particles organized as individual aggregates separated
      by particle-free regions. In this case, we suggest that some particles spread at
      the interface leading to the formation of a continuous protein membrane. Charged
      particles displayed the ability to bridge opposing interfaces of neighbouring
      drops to form dense particle disks protecting drops against coalescence; this is
      the main reason for the flocculation and stability of emulsions containing
      sparsely covered drops. 

PMID- 24675996
TI  - Comparative protein composition analysis of goat milk produced by the Alpine and
      Saanen breeds in northeastern Brazil and related antibacterial activities.
AB  - The protein composition of goat milk differs between goat breeds and could
      present regional trends. The aim of this study was to comparatively analyze the
      protein composition of goat milk produced by the Alpine and Saanen breeds in
      northeastern Brazil and to evaluate the antibacterial activity of its protein
      fractions. SDS-PAGE, 2-DE electrophoresis and RP-HPLC analyses revealed the
      absence of alphas1-casein in the milk of both breeds and no differences between
      the alphas2-casein, beta-casein, beta-lactoglobulin and alpha-lactalbumin
      profiles. The amounts of soluble proteins and beta-casein hydrolysis residues
      were higher in Saanen milk. Only the protein fraction containing the largest
      amounts of casein (F60-90%) inhibited bacterial growth, with MIC values between
      50 and 100 mg/mL. This study describe for the first time three important points
      about the goat milk protein of two Brazilian goat breeders: absence of alpha-s1
      casein in the protein profile, differences between the milk protein composition
      produced by goats of Alpine and Saanen breeders and antibacterial activity of
      unbroken proteins (casein-rich fraction) present in these milk. 

PMID- 24675995
TI  - Generation and analysis of novel plant-derived antibody-based therapeutic
      molecules against West Nile virus.
AB  - Previously, our group engineered a plant-derived monoclonal antibody (MAb) (pHu
      E16) that efficiently treated West Nile virus (WNV) infection in mice. In this
      study, we developed several pHu-E16 variants to improve its efficacy. These
      variants included a single-chain variable fragment (scFv) of pHu-E16 fused to the
      heavy chain (HC) constant domains (CH(1-3)) of human IgG (pHu-E16scFv-CH(1-3))
      and a tetravalent molecule (Tetra pHu-E16) assembled from pHu-E16scFv-CH(1-3)
      with a second pHu-E16scFv fused to the light chain (LC) constant region. pHu
      E16scFv-CH(1-3) and Tetra pHu-E16 were efficiently expressed and assembled in
      plants. To assess the impact of differences in N-linked glycosylation on pHu-E16
      variant assembly and function, we expressed additional pHu-E16 variants with
      various combinations of HC and LC components. Our study revealed that proper
      pairing of HC and LC was essential for the complete N-glycan processing of
      antibodies in both plant and animal cells. Associated with their distinct N
      glycoforms, pHu-E16, pHu-E16scFv-CH(1-3) and Tetra pHu-E16 exhibited differential
      binding to C1q and specific Fcgamma receptors (FcgammaR). Notably, none of the
      plant-derived Hu-E16 variants showed antibody-dependent enhancement (ADE)
      activity in CD32A+ human cells, suggesting the potential of plant-produced
      antibodies to minimize the adverse effect of ADE. Importantly, all plant-derived
      MAb variants exhibited at least equivalent in vitro neutralization and in vivo
      protection in mice compared to mammalian cell-produced Hu-E16. This study
      demonstrates the capacity of plants to express and assemble a large, complex and
      functional IgG-like tetravalent mAb variant and also provides insight into the
      relationship between MAb N-glycosylation, FcgammaR and C1q binding, and ADE.
      These new insights may allow the development of safer and cost effective MAb
      based therapeutics for flaviviruses, and possibly other pathogens.

PMID- 24675997
TI  - Bacterial profile of dentine caries and the impact of pH on bacterial population
      diversity.
AB  - Dental caries is caused by the release of organic acids from fermentative
      bacteria, which results in the dissolution of hydroxyapatite matrices of enamel
      and dentine. While low environmental pH is proposed to cause a shift in the
      consortium of oral bacteria, favouring the development of caries, the impact of
      this variable has been overlooked in microbial population studies. This study
      aimed to detail the zonal composition of the microbiota associated with carious
      dentine lesions with reference to pH. We used 454 sequencing of the 16S rRNA gene
      (V3-V4 region) to compare microbial communities in layers ranging in pH from 4.5
      7.8 from 25 teeth with advanced dentine caries. Pyrosequencing of the amplicons
      yielded 449,762 sequences. Nine phyla, 97 genera and 409 species were identified
      from the quality-filtered, de-noised and chimera-free sequences. Among the
      microbiota associated with dentinal caries, the most abundant taxa included
      Lactobacillus sp., Prevotella sp., Atopobium sp., Olsenella sp. and Actinomyces
      sp. We found a disparity between microbial communities localised at acidic versus
      neutral pH strata. Acidic conditions were associated with low diversity microbial
      populations, with Lactobacillus species including L. fermentum, L. rhamnosus and
      L. crispatus, being prominent. In comparison, the distinctive species of a more
      diverse flora associated with neutral pH regions of carious lesions included
      Alloprevotella tanerrae, Leptothrix sp., Sphingomonas sp. and Streptococcus
      anginosus. While certain bacteria were affected by the pH gradient, we also found
      that ~ 60% of the taxa associated with caries were present across the
      investigated pH range, representing a substantial core. We demonstrated that some
      bacterial species implicated in caries progression show selective clustering with
      respect to pH gradient, providing a basis for specific therapeutic strategies.

PMID- 24675998
TI  - Identification of new IkappaBalpha complexes by an iterative experimental and
      mathematical modeling approach.
AB  - The transcription factor nuclear factor kappa-B (NFkappaB) is a key regulator of
      pro-inflammatory and pro-proliferative processes. Accordingly, uncontrolled
      NFkappaB activity may contribute to the development of severe diseases when the
      regulatory system is impaired. Since NFkappaB can be triggered by a huge variety
      of inflammatory, pro-and anti-apoptotic stimuli, its activation underlies a
      complex and tightly regulated signaling network that also includes multi-layered
      negative feedback mechanisms. Detailed understanding of this complex signaling
      network is mandatory to identify sensitive parameters that may serve as targets
      for therapeutic interventions. While many details about canonical and non
      canonical NFkappaB activation have been investigated, less is known about
      cellular IkappaBalpha pools that may tune the cellular NFkappaB levels.
      IkappaBalpha has so far exclusively been described to exist in two different
      forms within the cell: stably bound to NFkappaB or, very transiently, as unbound
      protein. We created a detailed mathematical model to quantitatively capture and
      analyze the time-resolved network behavior. By iterative refinement with numerous
      biological experiments, we yielded a highly identifiable model with superior
      predictive power which led to the hypothesis of an NFkappaB-lacking IkappaBalpha
      complex that contains stabilizing IKK subunits. We provide evidence that other
      but canonical pathways exist that may affect the cellular IkappaBalpha status.
      This additional IkappaBalpha:IKKgamma complex revealed may serve as storage for
      the inhibitor to antagonize undesired NFkappaB activation under physiological and
      pathophysiological conditions. 

PMID- 24675999
TI  - Perfusion-based selection for endovascular reperfusion therapy in anterior
      circulation acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Controversy exists about the role of perfusion imaging in
      patient selection for endovascular reperfusion therapy in acute ischemic stroke.
      We hypothesized that perfusion imaging versus noncontrast CT- based selection
      would be associated with improved functional outcomes at 3 months. MATERIALS AND
      METHODS: We reviewed consecutive patients with anterior circulation strokes
      treated with endovascular reperfusion therapy within 8 hours and with baseline
      NIHSS score of >=8. Baseline clinical data, selection mode (perfusion versus
      NCCT), angiographic data, complications, and modified Rankin Scale score at 3
      months were collected. Using multivariable logistic regression, we assessed
      whether the mode of selection for endovascular reperfusion therapy (perfusion
      based versus NCCT-based) was independently associated with good outcome. RESULTS:
      Two-hundred fourteen patients (mean age, 67.2 years; median NIHSS score, 18; MCA
      occlusion 74% and ICA occlusion 26%) were included. Perfusion imaging was used in
      76 (35.5%) patients (39 CT and 37 MR imaging). Perfusion imaging-selected
      patients were more likely to have good outcomes compared with NCCT-selected
      patients (55.3 versus 33.3%, P = .002); perfusion selection by CT was associated
      with similar outcomes as that by MR imaging (CTP, 56.; MR perfusion, 54.1%; P =
      .836). In multivariable analysis, CT or MR perfusion imaging selection remained
      strongly associated with good outcome (adjusted OR, 2.34; 95% CI, 1.22-4.47),
      independent of baseline severity and reperfusion. CONCLUSIONS: In this
      multicenter study, patients with acute ischemic stroke who underwent perfusion
      imaging were more than 2-fold more likely to have good outcomes following
      endovascular reperfusion therapy. Randomized studies should compare perfusion
      imaging with NCCT imaging for patient selection for endovascular reperfusion
      therapy.

PMID- 24676001
TI  - The ins and outs of sexual imaging.

PMID- 24676000
TI  - Symptom differences and pretreatment asymptomatic interval affect outcomes of
      stenting for intracranial atherosclerotic disease.
AB  - BACKGROUND AND PURPOSE: Different types of symptomatic intracranial stenosis may
      respond differently to interventional therapy. We investigated symptomatic and
      pathophysiologic factors that may influence clinical outcomes of patients with
      intracranial atherosclerotic disease who were treated with stents. MATERIALS AND
      METHODS: A retrospective analysis was performed of patients treated with stents
      for intracranial atherosclerosis at 4 centers. Patient demographics and
      comorbidities, lesion features, treatment features, and preprocedural and
      postprocedural functional status were noted. chi(2) univariate and multivariate
      logistic regression analysis was performed to assess technical results and
      clinical outcomes. RESULTS: One hundred forty-two lesions in 131 patients were
      analyzed. Lesions causing hypoperfusion ischemic symptoms were associated with
      fewer strokes by last contact [chi(2) (1, n = 63) = 5.41, P = .019].
      Nonhypoperfusion lesions causing symptoms during the 14 days before treatment had
      more strokes by last contact [chi(2) (1, n = 136), 4.21, P = .047]. Patients
      treated with stents designed for intracranial deployment were more likely to have
      had a stroke by last contact (OR, 4.63; P = .032), and patients treated with
      percutaneous balloon angioplasty in addition to deployment of a self-expanding
      stent were less likely to be stroke free at point of last contact (OR, 0.60; P =
      .034). CONCLUSIONS: More favorable outcomes may occur after stent placement for
      lesions causing hypoperfusion symptoms and when delaying stent placement 7-14
      days after most recent symptoms for lesions suspected to cause embolic disease or
      perforator ischemia. Angioplasty performed in addition to self-expanding stent
      deployment may lead to worse outcomes, as may use of self-expanding stents rather
      than balloon-mounted stents.

PMID- 24676002
TI  - Hemorrhagic complications after endovascular treatment of cerebral arteriovenous
      malformations.
AB  - BACKGROUND AND PURPOSE: Intracranial hemorrhage is the most severe complication
      of brain arteriovenous malformation treatment. We report our rate of hemorrhagic
      complications after endovascular treatment and analyze the clinical significance
      and potential mechanisms, with emphasis on cases of delayed hemorrhage after
      uneventful embolization. MATERIALS AND METHODS: During a 10-year period, 846
      embolization procedures were performed in 408 patients with brain AVMs. Any cases
      of hemorrhagic complications were identified and divided into those related or
      unrelated to a periprocedural arterial tear (during catheter navigation or
      catheter retrieval). We analyzed the following variables: sex, age, hemorrhagic
      presentation, Spetzler-Martin grade, size of the AVM, number of embolized
      pedicles, microcatheter used, type and volume of liquid embolic agent injected,
      and the presence of a premature venous occlusion. Univariate and multivariate
      multiple regression analyses were performed to identify risk factors for
      hemorrhagic complications. RESULTS: A hemorrhagic complication occurred in 92
      (11%) procedures. Forty-four (48%) complications were related to a periprocedural
      arterial perforation, and 48 (52%) were not. Hemorrhagic complications unrelated
      to an arterial perforation were located more commonly in the cerebral parenchyma,
      caused more neurologic deficits, and were associated with worse prognosis than
      those in the arterial perforation group. Only premature venous occlusion was
      identified as an independent predictor of hemorrhagic complication in the
      nonperforation group. Premature venous occlusion was significantly related to the
      ratio of Onyx volume to nidus diameter. CONCLUSIONS: Higher injected volume of
      embolic agent and deposition on the venous outflow before complete occlusion of
      the AVM may account for severe hemorrhagic complications.

PMID- 24676003
TI  - Building multidevice pipeline constructs of favorable metal coverage: a practical
      guide.
AB  - BACKGROUND AND PURPOSE: The advent of low-porosity endoluminal devices, also
      known as flow diverters, exemplified by the Pipeline in the United States,
      produced the greatest paradigm shift in cerebral aneurysm treatment since the
      introduction of detachable coils. Despite robust evidence of efficacy and safety,
      key questions regarding the manner of their use remain unanswered. Recent studies
      demonstrated that the Pipeline device geometry can dramatically affect its metal
      coverage, emphasizing the negative effects of oversizing the device relative to
      its target vessels. This follow-up investigation focuses on the geometry and
      coverage of multidevice constructs. MATERIALS AND METHODS: A number of Pipeline
      devices were deployed in tubes of known diameters and photographed, and the
      resultant coverage was determined by image segmentation. Multidevice segmentation
      images were created to study the effects of telescoped devices and provide an
      estimate of coverages resulting from device overlap. RESULTS: Double overlap
      yields a range of metal coverage, rather than a single value, determined by the
      diameters of both devices, the size of the recipient artery, and the degree to
      which strands of the overlapped devices are coregistered with each other. The
      potential variation in coverage is greatest during overlap of identical-diameter
      devices, for example, ranging from 24% to 41% for two 3.75-mm devices deployed in
      a 3.5-mm vessel. Overlapping devices of progressively different diameters produce
      correspondingly more uniform ranges of coverage, though reducing the maximum
      achievable value, for example, yielding a 33%-34% range for 3.75- and 4.75-mm
      devices deployed in the same 3.5-mm vessel. CONCLUSIONS: Rational strategies for
      building multidevice constructs can achieve favorable geometric outcomes.

PMID- 24676004
TI  - Low-power inversion recovery MRI preserves brain tissue contrast for patients
      with Parkinson disease with deep brain stimulators.
AB  - BACKGROUND AND PURPOSE: Fast spin-echo short tau inversion recovery sequences
      have been very useful for MR imaging-guided deep brain stimulation procedures in
      Parkinson disease. However, high-quality fast spin-echo imaging deposits
      significant heat, exceeding FDA-approved limits when patients already have
      undergone deep brain stimulation and need a second one or a routine brain MR
      imaging for neurologic indications. We have developed a STIR sequence with an
      ultra-low specific absorption rate that meets hardware limitations and produces
      adequate tissue contrast in cortical and subcortical brain tissues for deep brain
      stimulation recipients. MATERIALS AND METHODS: Thirteen patients with medically
      refractory Parkinson disease who qualified for deep brain stimulation were imaged
      at 1.5T with a fast spin-echo short tau inversion recovery sequence modified to
      meet conditional MR imaging hardware and specific absorption rate restrictions.
      Tissue contrast-to-noise ratios and implant localization were objectively and
      subjectively compared by 2 neuroradiologists, and image quality for surgical
      planning was assessed by a neurosurgeon for high and low specific absorption rate
      images. RESULTS: The mean contrast-to-noise ratio for cerebral tissues without
      including the contrast-to-noise ratio for ventricular fluid was 35 and 31 for
      high and low specific absorption rate images. Subjective ratings for low specific
      absorption rate tissue contrast in 77% of patients were identical to (and in a
      few cases higher than) those of high specific absorption rate contrast, while the
      neurosurgical coordinates for fusing the stereotactic atlas with low specific
      absorption rate MR imaging were equivalent to those of the high specific
      absorption rate for 69% of patients. CONCLUSIONS: Patients with Parkinson disease
      who have already had a deep brain stimulation face a risk of neural injury if
      routine, high specific absorption rate MR imaging is performed. Our modified fast
      spin-echo short tau inversion recovery sequence conforms to very conservative
      radiofrequency safety limits, while it maintains high tissue contrast for
      presurgical planning, postsurgical assessment, and radiologic evaluations with
      greater confidence for radiofrequency safety.

PMID- 24676005
TI  - Differentiation of tumor progression from pseudoprogression in patients with
      posttreatment glioblastoma using multiparametric histogram analysis.
AB  - BACKGROUND AND PURPOSE: The multiparametric imaging can show us different aspects
      of tumor behavior and may help differentiation of tumor recurrence from treatment
      related change. Our aim was to differentiate tumor progression from
      pseudoprogression in patients with glioblastoma by using multiparametric
      histogram analysis of 2 consecutive MR imaging studies with relative cerebral
      blood volume and ADC values. MATERIALS AND METHODS: Thirty-five consecutive
      patients with glioblastoma with new or increased size of enhancing lesions after
      concomitant chemoradiation therapy following surgical resection were included.
      Combined histograms were made by using the relative cerebral blood volume and ADC
      values of enhancing areas for initial and follow-up MR imaging, and subtracted
      histograms were also prepared. The histogram parameters between groups were
      compared. The diagnostic accuracy of tumor progression based on the histogram
      parameters of initial and follow-up MR imaging and subtracted histograms was
      compared and correlated with overall survival. RESULTS: Twenty-four
      pseudoprogressions and 11 tumor progressions were determined. Diagnosis based on
      the subtracted histogram mode with a multiparametric approach was more accurate
      than the diagnosis based on the uniparametric approach (area under the receiver
      operating characteristic curve of 0.877 versus 0.801), with 81.8% sensitivity and
      100% specificity. A high mode of relative cerebral blood volume on the subtracted
      histogram by using a multiparametric approach (relative cerebral blood volume
      *ADC) was the best predictor of true tumor progression (P < .001) and worse
      survival (P = .003). CONCLUSIONS: Multiparametric histogram analysis of
      posttreatment glioblastoma was useful to predict true tumor progression and worse
      survival.

PMID- 24676006
TI  - PET in infancy predicts long-term outcome during adolescence in cryptogenic West
      syndrome.
AB  - BACKGROUND AND PURPOSE: Developmental and seizure outcomes in patients with
      cryptogenic West syndrome are variable. Our aim was to clarify the relationship
      between FDG-PET findings in infancy and long-term seizure and developmental
      outcome in cryptogenic West syndrome. MATERIALS AND METHODS: From 1991 to 1999,
      we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in
      27 patients. PET was performed at onset and at 10 months of age. In 2012, we
      evaluated the educational status, psychomotor development, and seizure outcome in
      23 of the 27 patients (13-22 years of age). The correlation between PET findings
      and outcome was evaluated. RESULTS: At onset, PET showed hypometabolism in 13
      patients (57%). The second PET after the initial treatment revealed cortical
      hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on
      the second PET in 9 patients, it was newly revealed in 3 patients on the second
      PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients
      had intellectual impairment. The first PET did not correlate with seizure or
      developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the
      second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients
      with normal findings on the second PET were free of seizures. Five of 7 patients
      (71%) showing hypometabolism on the second PET had intellectual impairment.
      Thirteen of 16 (81%) patients with normal findings on the second PET showed
      normal intelligence. A significant correlation was found between the second PET
      and long-term seizure (P = .01) or developmental outcome (P = .03). CONCLUSIONS:
      Cortical hypometabolism is not permanent; it changes with clinical symptoms.
      Hypometabolism after initial treatment predicts long-term seizures and poor
      developmental outcome.

PMID- 24676009
TI  - Strain localization in glassy polymers under cylindrical confinement.
AB  - Although the origin of ductility in crystalline materials is well understood
      through the motion of dislocations and defects, a similar framework for
      understanding deformation in amorphous materials remains elusive. In particular,
      the difference in the mechanical response for small-molecule amorphous solids,
      such as organic glasses that are typically brittle, and polymer glasses, which
      are frequently very tough, has not been systematically explored. Here, we employ
      molecular dynamics simulations to investigate the mechanical response of model
      glassy polymers confined to a nanoscopic pillar under tensile deformation. We
      vary the chain length, cooling rate for forming the glass, and the deformation
      rate and investigate the changes in the mechanical response. We find that samples
      that are cooled at a slower rate and deformed at a slower rate are more prone to
      localization of the strain response, or shear banding. Interestingly, this effect
      is independent of chain length over the range of parameters we have investigated
      so far, and we believe this is the first direct observation of shear banding in
      deformed polymer glasses under cylindrical confinement. Finally, by using the
      isoconfigurational ensemble approach, we provide evidence that the location where
      the shear band forms is due to structural features that are frozen in place
      during sample preparation. 

PMID- 24676008
TI  - The diagnostic value of CT myelography, MR myelography, and both in neonatal
      brachial plexus palsy.
AB  - BACKGROUND AND PURPOSE: Although most infants with brachial plexus palsy recover
      function spontaneously, approximately 10-30% benefit from surgical treatment. Pre
      operative screening for nerve root avulsions is helpful in planning
      reconstruction. Our aim was to compare the diagnostic value of CT myelography, MR
      myelography, and both against a surgical criterion standard for detection of
      complete nerve root avulsions in birth brachial plexus palsy. MATERIALS AND
      METHODS: Nineteen patients who underwent a preoperative CT and/or MR myelography
      and subsequent brachial plexus exploration were included. Imaging studies were
      analyzed for the presence of abnormalities potentially predictive of nerve root
      avulsion. Findings of nerve root avulsion on surgical exploration were used as
      the criterion standard to assess the predictive value of imaging findings.
      RESULTS: Ninety-five root levels were examined. When the presence of any
      pseudomeningocele was used as a predictor, the sensitivity was 0.73 for CT and
      0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging.
      When presence of pseudomeningocele with absent rootlets was used as the
      predictor, the sensitivity was 0.68 for CT and 0.68 for MR imaging and the
      specificity was 0.96 for CT and 0.97 for MR imaging. The use of both CT and MR
      imaging did not increase diagnostic accuracy. Rootlet findings in the absence of
      pseudomeningocele were not helpful in predicting complete nerve root avulsion.
      CONCLUSIONS: Findings of CT and MR myelography were highly correlated. Given the
      advantages of MR myelography, it is now the single technique for preoperative
      evaluation of nerve root avulsion at our institution.

PMID- 24676007
TI  - Safety of unilateral endovascular occlusion of the cervical segment of the
      vertebral artery without antecedent balloon test occlusion.
AB  - BACKGROUND AND PURPOSE: Antecedent balloon test occlusion is often performed
      prior to vertebral artery sacrifice, but there is limited data to suggest this
      adds a significant clinical benefit, especially in the setting of trauma.
      Furthermore, balloon test occlusion can be time-consuming, add to the technical
      complexity of the procedure, and increase the overall cost of treatment. The
      purpose of this study was to determine the safety of unilateral vertebral artery
      occlusion without antecedent balloon test occlusion as part of the treatment
      regimen in patients with traumatic vertebral artery dissection, cervical tumor,
      or intracranial aneurysm. MATERIALS AND METHODS: The medical records and imaging
      studies of 59 patients in whom unilateral endovascular cervical vertebral artery
      occlusion was performed were retrospectively reviewed. Procedure-related stroke
      was defined as imaging evidence of acute infarct in the vascular territories
      supplied by the occluded vertebral artery or new focal neurologic deficit
      developing in the first 30 days after vertebral artery occlusion attributable to
      infarction in the posterior circulation. RESULTS: Fifty-nine patients underwent
      unilateral endovascular cervical vertebral artery occlusion to prevent potential
      thromboembolic complications of vertebral artery injury, for treatment of
      intracranial aneurysms, or for presurgical embolization of a cervical vertebral
      tumor. Unilateral occlusion was performed when endovascular reconstruction was
      considered impossible or deemed more risky than deconstruction. Fifty-eight of
      the 59 patients underwent vertebral artery occlusion without antecedent balloon
      test occlusion. None of the 59 patients had clinical or imaging evidence of a
      postprocedural infarct. CONCLUSIONS: In this series, endovascular occlusion of a
      cervical segment of 1 vertebral artery was safely performed without antecedent
      balloon test occlusion. As long as both vertebral arteries were patent and
      converged at the vertebrobasilar junction, there was anatomic potential for
      retrograde filling of the distal intracranial vertebral artery to the level of
      the posterior inferior cerebellar artery origin, and there was no major vascular
      supply to the spinal cord arising from the target segment of the affected vessel.
      Dominant and nondominant vertebral arteries were safely occluded, and no infarcts
      were attributed to the treatment.

PMID- 24676011
TI  - [Should insulin resistance be always treated in Polycystic Ovary Syndrome?].

PMID- 24676010
TI  - The stratifying value of Hangzhou criteria in liver transplantation for
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The selection criteria for patients with hepatocellular
      carcinoma (HCC) as candidates for deceased donor liver transplantation (DDLT) are
      well studied. In this era of limited deceased donor organs, the value of living
      donor liver transplantation (LDLT) for HCC remains controversial. The aim of the
      present study was to verify the stratification value of the Hangzhou criteria for
      LDLT. METHODS: The data of 47 LDLT recipients and 94 matched DDLT recipients at
      our center were evaluated. Overall survival and tumor-free survival were
      calculated. Prognostic factors influencing post-liver transplantation (LT)
      survival were identified. The stratification values of the Hangzhou criteria and
      Milan criteria were compared. RESULTS: LDLT recipients spent much less time on
      the waiting list. The post-LT survival of recipients fulfilling the Milan
      criteria and recipients fulfilling the Hangzhou criteria were comparable
      (P>0.05). The overall and tumor-free survival did not differ statistically
      between the two groups. In both groups, more recipients not meeting the Milan
      criteria but with a satisfactory outcome were identified by the Hangzhou
      criteria. Among recipients who did not meet the Hangzhou criteria, tumor-free
      survival was better for the LDLT recipients than the DDLT recipients (P = 0.024).
      CONCLUSIONS: The Hangzhou criteria are reliable for stratifying HCC patients in
      terms of prognosis. HCC patients fulfilling the Hangzhou criteria gain
      satisfactory survival from LT. Outcomes after LDLT are better than those after
      DDLT for HCC patients who do not meet the Hangzhou criteria.

PMID- 24676012
TI  - [Pregnancy outcome and thrombophilia of women with recurrent fetal death].
AB  - PURPOSE: To evaluate pregnancy outcome and thrombophilia frequency in women with
      recurrent fetal death. METHODS: Evaluation of obstetric outcomes in a
      retrospective cohort of pregnant women with recurrent stillbirth after the 20th
      week, from 2001 to 2013. Antithrombin activity, protein C and S activity, factor
      V Leiden, prothrombin gene mutation and antiphospholipid syndrome were analyzed.
      RESULTS: We included 20 patients who had recurrent fetal death. Thrombophilia
      were found in 11 of them, 7 diagnosed with antiphospholipid syndrome, 3 with
      protein S deficiency and 1 with prothrombin gene mutation. All of them were
      treated with subcutaneous heparin (unfractionated heparin or enoxaparina) and 14
      of them with acetylsalicylic acid (AAS) during pregnancy. Obstetric complications
      occurred in 15 patients and included: intrauterine fetal growth restriction
      (25%), placenta previa (15%), reduced amniotic fluid index (25%), severe
      preeclampsia (10%), fetal distress (5%), and stillbirth (5%). The mean
      gestational age at delivery was 35.8 +/- 3.7 weeks and newborn weight averaged
      2,417.3 +/- 666.2 g. CONCLUSION: Thrombophilia screening should be performed in
      all pregnant women with recurrent fetal death after the 20th week as a way to
      identify possible causal factors suitable for treatment.

PMID- 24676013
TI  - [Adequacy process of prenatal care according to the criteria of humanizing of
      prenatal care and childbirth program and stork network].
AB  - PURPOSE: To evaluate the adequacy of the process of prenatal care according to
      the parameters of the Program for the Humanization of Prenatal Care (PHPN) and of
      the procedures provided by the Stork Network of Unified Health System (SUS) in
      the microregion of Espirito Santo state, Brazil. METHODS: A cross-sectional study
      was conducted in 2012-2013 by interviewing and analyzing the records of 742 women
      during the postpartum period and of their newborns in 7 hospitals in the region
      chosen for the research. The information was collected, processed and analyzed by
      the chi2 and Fisher's exact test to determine the difference in proportion
      between the criteria adopted by the PHPN and the Stork Network and the place of
      residence, family income and type of coverage of prenatal service. The level of
      significance was set at 5%. RESULTS: The parameters showing the lowest adequacy
      rate were quick tests and repeated exams, with frequencies around 10 and 30%,
      respectively, in addition to educational activities (57.9%) and tetanus
      immunization (58.7%). In contrast, risk management (92.6%) and the fasting plasma
      glucose test (91.3%) showed the best results. Adequacy was 7.4% for the PHPN,
      0.4% for the Stork Network, with respect to the parameters of normal risk
      pregnancies, and 0 for high risk pregnancies. There was a significant difference
      between puerperae according to housing location regarding the execution of
      serology for syphilis (VDRL), anti-HIV and repeated fasting glucose tests, and
      monthly income influenced the execution of blood type/Rh factor tests, VDRL,
      hematocrit and anti-HIV test. CONCLUSION: Prenatal care in the SUS proved to be
      inadequate regarding the procedures required by the PHPN and Stork Network in the
      micro-region of a state in southeastern Brazil, especially for women of lower
      income, PACS users and residents of rural areas.

PMID- 24676014
TI  - [Association between risk pregnancy and route of delivery with maternal and
      neonatal outcomes].
AB  - PURPOSE: To analyze the relationships among gestational risk, type of delivery
      and immediate maternal and neonatal repercussions. METHODS: A retrospective
      cohort study based on secondary data was conducted in a university maternity
      hospital. A total of 1606 births were analyzed over a 9-month period.
      Epidemiological, clinical, obstetric and neonatal characteristics were compared
      according to the route of delivery and the gestational risk characterized on the
      basis of the eligibility criteria for high clinical risk. The occurrence of
      maternal and neonatal complications during hospitalization was analyzed according
      to gestational risk and cesarean section delivery using univariate and
      multivariate logistic analysis. RESULTS: The overall rate of cesarean sections
      was 38.3%. High gestational risk was present in 50.2% of births, mainly
      represented by hypertensive disorders and fetal malformations. The total
      incidence of cesarean section, planned cesarean section or emergency cesarean
      section was more frequent in pregnant women at gestational high risk (p<0.001).
      Cesarean section alone did not influence maternal outcome, but was associated
      with poor neonatal outcome (OR 3.4; 95%CI 2.7-4.4). Gestational high risk was
      associated with poor maternal and neonatal outcome (OR 3.8; 95%CI 1.3-8.7 and OR
      17.5; 95%CI 11.6-26.3, respectively). In multivariate analysis, the ratios were
      maintained, although the effect of gestational risk has determined a reduction in
      the OR of the type of delivery alone from 3.4 (95%CI 2.7-4.4) to 1.99 (95%CI 1.5
      2.6) for adverse neonatal outcome. CONCLUSION: Gestational risk was the main
      factor associated with poor maternal and neonatal outcome. Cesarean delivery was
      not directly associated with poor maternal outcome but increased the chances of
      unfavorable neonatal outcomes.

PMID- 24676015
TI  - Salivary and serum cortisol levels, salivary alpha-amylase and unstimulated whole
      saliva flow rate in pregnant and non-pregnant.
AB  - PURPOSE: To compare salivary and serum cortisol levels, salivary alpha-amylase
      (sAA), and unstimulated whole saliva (UWS) flow rate in pregnant and non-pregnant
      women. METHOD: A longitudinal study was conducted at a health promotion center of
      a university hospital. Nine pregnant and 12 non-pregnant women participated in
      the study. Serum and UWS were collected and analyzed every trimester and twice a
      month during the menstrual cycle. The salivary and serum cortisol levels were
      determined by chemiluminescence assay and the sAA was processed in an automated
      biochemistry analyzer. RESULTS: Significant differences between the pregnant and
      non-pregnant groups were found in median [interquartile range] levels of serum
      cortisol (23.8 uL/dL [19.4-29.4] versus 12.3 [9.6-16.8], p<0.001) and sAA (56.7
      U/L [30.9-82.2] versus 31.8 [18.1-53.2], p<0.001). Differences in salivary and
      serum cortisol (uL/dL) and sAA levels in the follicular versus luteal phase were
      observed (p<0.001). Median UWS flow rates were similar in pregnant (0.26 [0.15
      0.30] mL/min) and non-pregnant subjects (0.23 [0.20-0.32] mL/min). Significant
      correlations were found between salivary and serum cortisol (p=0.02) and between
      salivary cortisol and sAA (p=0.01). CONCLUSIONS: Serum cortisol and sAA levels
      are increased during pregnancy. During the luteal phase of the ovarian cycle,
      salivary cortisol levels increase, whereas serum cortisol and sAA levels decline.

PMID- 24676016
TI  - [Depressive symptoms in women with chronic pelvic pain].
AB  - PURPOSE: To investigate the presence of depressive symptoms in women with chronic
      pelvic pain. METHODS: This descriptive cross-sectional study was performed with
      women aged 18 years or older, diagnosed with chronic pelvic pain, with no
      pregnancy history in the previous year, and with no cancer history. The sample
      was established by calculating the representative sample, estimated as 50 women.
      All women were undergoing treatment at a gynecology outpatient clinic, referred
      by the primary health care network of the Brazilian national health system. Data
      collection was performed from October 2009 to May 2010. The women's
      sociodemographic, economic and clinical characteristics were analyzed. Pain
      intensity was evaluated using a visual analogue scale. The depressive symptoms
      were investigated using Beck's Depression Inventory. Statistical analysis was
      performed using position measures (mean, median), dispersion (standard deviation)
      and the chi2 test. Values of p <= .05 were considered statistically significant.
      RESULTS: The participants' mean age was 41.6 +/- 9.4 years. The following
      features predominated: secondary education level; pardo (brown) skin color;
      Catholic religion; and living with a steady partner. Most (98%) were economically
      active and worked with general domestic services. Regarding the participants'
      subjective perception of pain, 52% reported experiencing intense pain, while 48%
      reported experiencing moderate pain. Most women (52%) had been living with pain
      for five years or less, and 30%, for over 11 years. The mean BDI score was 17.4
      (+/- 9.4). It was observed that 58% of the women presented mild, moderate and
      severe depressive symptoms according to the BDI. The most frequent depressive
      symptoms were fatigability, loss of libido, irritability, difficulty to work,
      somatic preoccupations, crying, dissatisfaction, sadness, and insomnia.
      CONCLUSION: Depressive symptoms were frequent among these women suffering with
      chronic pelvic pain.

PMID- 24676017
TI  - [Influence of body mass index, body fat percentage and age at menarche on aerobic
      capacity (VO2 max) of elementary school female students].
AB  - PURPOSE: To identify and relate body fat percentage (skin fold measures), body
      mass index (BMI) and age at menarcheto aerobic capacity using the indirect VO2
      maximum value (VO2 max) of girls in the second cycle of primary school. METHODS:
      A total of 197 girls aged 13.0 +/- 1.2 years on average, students from two public
      schools in the city of Atibaia in Sao Paulo, were evaluated. Anthropometric
      evaluation of skin folds was performed using the Slaughter protocol for teenage
      girls, and BMI (kg/m2) was based on "Z score" (graphic of percentile) according
      to WHO recommendations. The Leger protocol was used to determine VO2 max. Pearson
      linear regression and the Student t-test were used for statistical analysis.
      RESULTS: 22.3% of the girls were overweight and 3.5% were obese according to the
      classification proposed by the WHO; 140 (71.1%) girls reported menarche. The
      average age at menarche was 12.0 +/- 1.0 years and was significantly higher in
      the group with normal BMI (12.2 +/- 0.9 years) than in the overweight or obese
      groups (11.6 +/- 1.0 years). The average indirect VO2 max value was 39.6 +/- 3.7
      mL/kg/min, ranging from 30.3 to 50.5 mL/kg/min. The advance of chronological age
      and early age at menarche were positively correlated with lower VO2 max values.
      CONCLUSIONS: This study showed that 25.8% of the girls had aBMI value above WHO
      recommendations. Girls with higher BMI and higher body fat percentage had lower
      VO2 max. The earlier age at menarche and the advance of chronological age were
      the most important factors for the reduction of aerobic capacity. The ageat
      menarche was higher in girls with adequate BMI compared tooverweight or obese
      girls.

PMID- 24676018
TI  - [Frequency of sleep disturbances in overweight/obese postmenopausal women].
AB  - PURPOSE: To evaluate the frequency of sleep disorders, such as obstructive sleep
      apnea, restless leg syndrome and insomnia in overweight/obese postmenopausal
      women seen in a climacteric sleep disorders clinic. METHODS: Thirty-four
      postmenopausal women were selected using the following inclusion criteria: age
      between 50 and 70 years; at least 12 months of amenorrhea; body mass index (BMI)
      greater than or equal to 25 kg/m2; and sleep-related complaints with at least one
      previous polysomnography. Patients provided responses to 6 questionnaires related
      to sleep characteristics and menopausal symptoms. Weight and height were measured
      using standardized scales, and abdomen and hip circumferences were also measured.
      The statistical analyses were performed using the chi2 test for qualitative
      variables and using Student's t-test for quantitative variables. RESULTS:
      Patients' characteristics were as follows: mean age of 60.35 years; mean BMI of
      31.62; an average of 11.61 postmenopausal years and an average Kupperman Index of
      19. A total of 85.2% of the patients had a waist/hip ratio of less than 0.8. The
      Epworth Scale score was greater than or equal to 9 in 50% of patients; 68% had
      sleep disturbances according to the Pittsburgh Index, and 68% were classified as
      high-risk for sleep apnea by the Berlin Questionnaire. On polysomnography, 70.58%
      of the patients had a sleep efficiency lower than 85%; 79.41% had a sleep latency
      of less than 30 min; 58.82% had a REM sleep latency of less than 90 min, and
      44.11% had mild apnea. When the groups were compared, a linear association was
      identified between BMI and the AHI average, and a relationship between high BMI
      and use of drugs for thyroid treatment was found. CONCLUSION: There was a high
      prevalence of sleep-disordered breathing, initial insomnia, fragmented sleep, and
      thyroid disorders in the group with higher BMI.

PMID- 24676019
TI  - Quantitative stratification of diffuse parenchymal lung diseases.
AB  - Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread
      pathological changes within the pulmonary tissue that impair the elasticity and
      gas exchange properties of the lungs. Clinical-radiological diagnosis of these
      diseases remains challenging and their clinical course is characterized by
      variable disease progression. These challenges have hindered the introduction of
      robust objective biomarkers for patient-specific prediction based on specific
      phenotypes in clinical practice for patients with DPLD. Therefore, strategies
      facilitating individualized clinical management, staging and identification of
      specific phenotypes linked to clinical disease outcomes or therapeutic responses
      are urgently needed. A classification schema consistently reflecting the
      radiological, clinical (lung function and clinical outcomes) and pathological
      features of a disease represents a critical need in modern pulmonary medicine.
      Herein, we report a quantitative stratification paradigm to identify subsets of
      DPLD patients with characteristic radiologic patterns in an unsupervised manner
      and demonstrate significant correlation of these self-organized disease groups
      with clinically accepted surrogate endpoints. The proposed consistent and
      reproducible technique could potentially transform diagnostic staging, clinical
      management and prognostication of DPLD patients as well as facilitate patient
      selection for clinical trials beyond the ability of current radiological tools.
      In addition, the sequential quantitative stratification of the type and extent of
      parenchymal process may allow standardized and objective monitoring of disease,
      early assessment of treatment response and mortality prediction for DPLD
      patients. 

PMID- 24676020
TI  - Dependence of coupling of quasi 2-D MoS2 with substrates on substrate types,
      probed by temperature dependent Raman scattering.
AB  - This work reports a study on the temperature dependence of in-plane E and out-of
      plane A1g Raman modes of single-layer (1L) and bi-layer (2L) MoS2 films on
      sapphire (epitaxial) and SiO2 (transferred) substrates as well as bulk MoS2
      single crystals in a temperature range of 25-500  degrees C. For the films on the
      transferred SiO2 substrate, the in-plane E mode is only weakly affected by the
      substrate, whereas the out-of-plane A1g mode is strongly perturbed, showing
      highly nonlinear, sometimes even non-monotonic, temperature dependence on the
      Raman peak shift and linewidth. In contrast, for the films on the epitaxial
      sapphire substrate, E is affected more significantly by the substrate than A1g.
      This study suggests that the 2-D film-substrate coupling depends sensitively on
      the preparation method, and in particular on the film morphology for the
      transferred film. These findings are vitally important for the fundamental
      understanding and application of this quasi 2-D material that is expected to be
      supported by a substrate in most circumstances. 

PMID- 24676021
TI  - Automated motion artifact removal for intravital microscopy, without a priori
      information.
AB  - Intravital fluorescence microscopy, through extended penetration depth and
      imaging resolution, provides the ability to image at cellular and subcellular
      resolution in live animals, presenting an opportunity for new insights into in
      vivo biology. Unfortunately, physiological induced motion components due to
      respiration and cardiac activity are major sources of image artifacts and impose
      severe limitations on the effective imaging resolution that can be ultimately
      achieved in vivo. Here we present a novel imaging methodology capable of
      automatically removing motion artifacts during intravital microscopy imaging of
      organs and orthotopic tumors. The method is universally applicable to different
      laser scanning modalities including confocal and multiphoton microscopy, and
      offers artifact free reconstructions independent of the physiological motion
      source and imaged organ. The methodology, which is based on raw data acquisition
      followed by image processing, is here demonstrated for both cardiac and
      respiratory motion compensation in mice heart, kidney, liver, pancreas and dorsal
      window chamber. 

PMID- 24676024
TI  - Highlight: Changing the canon--revisiting a classic experiment to alter the
      genetic code.

PMID- 24676025
TI  - Methadone and oedema in the palliative care setting: a case report and review of
      the literature.
AB  - INTRODUCTION: Methadone is a synthetic opioid which is being used with increased
      frequency in the palliative care setting for management of complex pain. There
      have been cases published reporting the development of oedema with methadone
      maintenance therapy but no cases on the association with methadone and peripheral
      oedema in the palliative care setting. As yet, the underlying mechanisms are
      unclear. CASE PRESENTATION: This case report describes a gentleman with
      ependymoma and difficult-to-control lower back pain and scrotal pain. This pain
      had failed to respond to other strong opioids. He was prescribed methadone and
      then subsequently developed bilateral peripheral oedema. CASE MANAGEMENT:
      Peripheral oedema resolved following cessation of methadone. CONCLUSIONS: This
      highlights an important potential adverse effect of methadone in a society of
      increased methadone prescription for pain control. The published literature to
      date is reviewed and possible underlying mechanisms explored.

PMID- 24676022
TI  - Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2)
      gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome.
AB  - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare
      disorder of enteric smooth muscle function affecting the intestine and bladder.
      Patients with this severe phenotype are dependent on total parenteral nutrition
      and urinary catheterization. The cause of this syndrome has remained a mystery
      since Berdon's initial description in 1976. No genes have been clearly linked to
      MMIHS. We used whole-exome sequencing for gene discovery followed by targeted
      Sanger sequencing in a cohort of patients with MMIHS and intestinal pseudo
      obstruction. We identified heterozygous ACTG2 missense variants in 15 unrelated
      subjects, ten being apparent de novo mutations. Ten unique variants were
      detected, of which six affected CpG dinucleotides and resulted in missense
      mutations at arginine residues, perhaps related to biased usage of CpG containing
      codons within actin genes. We also found some of the same heterozygous mutations
      that we observed as apparent de novo mutations in MMIHS segregating in families
      with intestinal pseudo-obstruction, suggesting that ACTG2 is responsible for a
      spectrum of smooth muscle disease. ACTG2 encodes gamma2 enteric actin and is the
      first gene to be clearly associated with MMIHS, suggesting an important role for
      contractile proteins in enteric smooth muscle disease. 

PMID- 24676026
TI  - At-admission risk stratification for in-hospital life-threatening ventricular
      arrhythmias and death in non-ST elevation myocardial infarction patients.
AB  - AIMS: Identification of patients with non-ST elevation acute myocardial
      infarction (NSTEMI) at higher risk of in-hospital life-threatening ventricular
      arrhythmias (LT-VA) and death is crucial for determining appropriate levels of
      care/monitoring during hospitalisation. We assessed predictors of in-hospital LT
      VA and all-cause mortality in a consecutive series of NSTEMI patients. METHODS
      AND RESULTS: We prospectively studied 1325 consecutive patients (69.7% males,
      median age 70 (61-79) years) presenting with NSTEMI and undergoing continuous
      electrocardiographic monitoring. The primary study end-point was the occurrence
      of spontaneous (unrelated to coronary interventions) in-hospital LT-VA, including
      sustained ventricular tachycardia and ventricular fibrillation; the secondary end
      point was in-hospital mortality from all causes. Of 1325 patients, 21 (1.5%)
      experienced LT-VA and 62 (4.7%) died from either arrhythmias (n=1) or other
      causes (n=61). Seven of the 20 patients who survived LT-VA subsequently died of
      heart failure. Independent predictors of in-hospital LT-VA were the Global
      Registry of Acute Coronary Events (GRACE) score >140 (odds ratio (OR)=7.5; 95%
      confidence interval (CI) 1.7-33.3; p=0.008) and left ventricular ejection
      fraction (LV-EF)<35% (OR=4.1; 95% CI 1.7-10.3; p=0.002). GRACE score >140
      (OR=14.6; 95% CI 3.4-62) and LV-EF <35% (OR=4.4; 95% CI 1.9-10) also predicted in
      hospital all-cause death. The cumulative probability of in-hospital LT-VA and
      death was respectively 9.2% and 23% in the 98 (7.4%) patients with GRACE score
      >140 and LV-EF<35%, while it was respectively 0.2% and 0% among the 627 (47.3%)
      with GRACE score <=140 and LV-EF >=35%. CONCLUSIONS: Simple risk stratification
      at admission based on GRACE score and echocardiographic LV-EF allows early
      identification of NSTEMI patients at higher risk of both in-hospital LT-VA and
      all-cause mortality.

PMID- 24676027
TI  - Prognostic value of admission glycated haemoglobin in unknown diabetic patients
      with acute myocardial infarction.
AB  - BACKGROUND: Acute glycometabolic derangement in non-diabetic patients with acute
      myocardial infarction (AMI) has been reported with discrepant prognostic results.
      The aim of the present study was to assess the prognostic impact of glycated
      haemoglobin (HbA1c) levels, reflecting long-term glycometabolic disturbance, in a
      population of patients without known diabetes mellitus. METHODS: We examined 601
      consecutive prospective patients diagnosed with AMI and unknown diabetes
      mellitus. We analysed metabolic function as a stratified variable using three
      groups of patients according to HbA1c: Group 1 (< 5.5%): 222 patients (37%);
      Group 2 (5.5 to 6.4%): 337 patients (56%); Group 3 (>6.4%): 42 patients (7%).
      Association between HbA1c groups and classic cardiovascular risk factor and in
      hospital outcomes were assessed through univariate and multivariate analysis.
      RESULTS: In-hospital mortality was 5% (32/601 patients). Higher HbA1c was
      associated with poor glycometabolic control, older patients, obesity,
      hypertension, Killip's class>1, increased heart rate, initial bundle branch
      block, atrial fibrillation and higher mortality during follow-up. In a
      multivariate adjusted risk, in-hospital mortality was associated with age (odds
      ratio (OR)= 1.056; 1-1.1; p=0.006), Killip's class>1 (OR=2.4; 1-6.1; p=0.05) and
      HbA1c (OR=1.5; 1.15-1.9; p=0.002). Hypertension (OR=0.39; 0.18-0.87; p=0.022) and
      angiotensin-converting enzyme inhibitors (OR=0.28; 0.12-0.69; p=0.005) were
      protective factors. CONCLUSIONS: HbA1c is an important risk marker in the absence
      of a history of diabetes mellitus in patients with AMI. The optimal management
      strategy in these patients may contribute to decreased in-hospital mortality.

PMID- 24676028
TI  - Decreased serum zinc is an effect of ageing and not Alzheimer's disease.
AB  - We examined the distribution of zinc in the periphery (erythrocytes and serum) in
      a large, well-characterised cohort, the Australian Imaging, Biomarkers and
      Lifestyle (AIBL) study, in order to determine if there is systemic perturbation
      in zinc homeostasis in Alzheimer's disease (AD). We observed an age dependent
      decrease in serum zinc of approximately 0.4% per year. When correcting for the
      age dependent decline in serum zinc no significant difference between healthy
      controls (HC), mildly cognitively impaired (MCI) or AD subjects was observed. 

PMID- 24676029
TI  - The role of erythropoietin and bone marrow concentrate in the treatment of
      osteochondral defects in mini-pigs.
AB  - BACKGROUND: All available treatment options for osteochondral and chondral
      defects do not restore hyaline cartilage and are limited to decreasing associated
      pain, and maintaining or improving joint function. The purpose of this study was
      to evaluate the potential of erythropoietin (EPO) in combination with bone marrow
      aspiration concentrate (BMAC) in the treatment of osteochondral defects of mini
      pigs. METHODS: 14 Goettinger mini-pigs, in which a 6 * 10 mm osteochondral defect
      in the medial femoral condyle of both knee joints was created, were randomized
      into four groups: biphasic scaffold alone, scaffold with EPO, scaffold with BMAC
      and scaffold in combination with EPO and BMAC. After 26 weeks all animals were
      euthanized and histological slides were evaluated using a modified ODriscoll
      Score. RESULTS: In the therapy groups, areas of chondrogenic tissue that
      contained collagen II were present. Adding EPO (p = 0.245) or BMAC (p = 0.099)
      alone to the scaffold led to a non-significant increase in the score compared to
      the control group. However, the combination of EPO and BMAC in the implanted
      scaffold showed a significant improvement (p = 0.02) in the histological score.
      CONCLUSION: The results of our study show that in mini-pigs, the combination of
      EPO and BMAC leads to an enhanced osteochondral healing. However, additional
      research is necessary to further improve the repair tissue and to define the role
      of MSCs and EPO in cartilage repair.

PMID- 24676030
TI  - Transgenic expression of a functional fragment of harpin protein Hpa1 in wheat
      induces the phloem-based defence against English grain aphid.
AB  - The harpin protein Hpa1 has multiple beneficial effects in plants, promoting
      plant growth and development, increasing crop yield, and inducing resistance to
      pathogens and insect pests. For these effects, the 10-40 residue fragment (Hpa110
      42) isolated from the Hpa1 sequence is 1.3- to 7.5-fold more effective than the
      full-length protein. Here it is reported that the expression of Hpa110-42 under
      the direction of an insect-induced promoter induces the phloem-based defence to
      English grain aphid, a dominant species of wheat aphids. The expression of Hpa110
      42 was found to compromise the colonization preference of aphids on the plant and
      further inhibit aphid reproduction in leaf colonies. In Hpa110-42-expressing
      wheat lines, moreover, aphid feeding from the phloem was repressed in correlation
      with the phloem-based defence. This defensive mechanism was shown as enhanced
      expression of wheat genes encoding phloem lectin proteins (PP2-A1 and PP2-A2) and
      beta-1,3-glucan synthase-like enzymes (GSL2, GSL10, and GSL12). Both PP2-A and
      beta-1,3-glucan formed high molecular mass polymers to block phloem sieve plate
      pores and therefore impede aphid feeding from the phloem. However, the phloem
      based defence was impaired by treating plants with ethylene signalling
      inhibitors, suggesting the requirement for the ethylene signalling pathway. In
      addition, if Hpa110-42-expressing plants were subjected to attack by a small
      number of aphids, they newly acquired agriculturally beneficial characters, such
      as enhanced vegetative growth and increased tiller numbers and grain output
      values. These results suggest that the defensive and developmental roles of
      Hpa110-42 can be integrated into the germplasm of this agriculturally significant
      crop.

PMID- 24676031
TI  - Carbon isotope discrimination during branch photosynthesis of Fagus sylvatica:
      field measurements using laser spectrometry.
AB  - On-line measurements of photosynthetic carbon isotope discrimination ((13)Delta)
      under field conditions are sparse. Hence, experimental verification of the
      natural variability of instantaneous (13)Delta is scarce, although (13)Delta is,
      explicitly and implicitly, used from leaf to global scales for inferring
      photosynthetic characteristics. This work presents the first on-line field
      measurements of (13)Delta of Fagus sylvatica branches, at hourly resolution,
      using three open branch bags and a laser spectrometer for CO2 isotopologue
      measurements (QCLAS-ISO). Data from two August/September field campaigns, in 2009
      and 2010, in a temperate forest in Switzerland are shown. Diurnal variability of
      (13)Delta was substantial, with mean diurnal amplitudes of ~90/00 and maximum
      diurnal amplitudes of ~200/00. The highest (13)Delta were generally observed
      during early morning and late afternoon, and the lowest (13)Delta during midday.
      An assessment of propagated standard deviations of (13)Delta demonstrated that
      the observed diurnal variation of (13)Delta was not a measurement artefact. Day
      to-day variations of (13)Delta were summarized with flux-weighted daily means of
      (13)Delta, which ranged from 150/00 to 230/00 in 2009 and from 180/00 to 290/00
      in 2010, thus displaying a considerable range of 8-110/00. Generally, (13)Delta
      showed the expected negative relationship with intrinsic water use efficiency.
      Diurnal and day-to-day variability of (13)Delta was, however, always better
      predicted by that of net CO2 assimilation, especially in 2010 when soil moisture
      was high and vapour pressure deficit was low. Stomatal control of leaf gas
      exchange, and consequently (13)Delta, could only be identified under drier
      conditions in 2009.

PMID- 24676033
TI  - The mechanism of NaFePO4 (de)sodiation determined by in situ X-ray diffraction.
AB  - The reaction mechanism occurring during the (de)intercalation of sodium into the
      host olivine FePO4 structure is thoroughly analysed through a combination of
      structural and electrochemical methods. In situ XRD experiments have confirmed
      that the charge and discharge reaction mechanisms are different and have revealed
      the existence of a solid solution domain from 1 < x < 2/3 in Na(x)FePO4 upon
      charge. The second part of the charge proceeds through a 2-phase reaction between
      Na(2/3)FePO4 and FePO4 with strongly varying solubility limits. The strong cell
      mismatch between Na(2/3)FePO4 and FePO4 enhances the effects of the diffuse
      interface and therefore varying solubility limits are first observed here in
      micrometric materials.

PMID- 24676032
TI  - Isoprene improves photochemical efficiency and enhances heat dissipation in
      plants at physiological temperatures.
AB  - Isoprene-emitting plants are better protected against thermal and oxidative
      stresses. Isoprene may strengthen membranes avoiding their denaturation and may
      quench reactive oxygen and nitrogen species, achieving a similar protective
      effect. The physiological role of isoprene in unstressed plants, up to now, is
      not understood. It is shown here, by monitoring the non-photochemical quenching
      (NPQ) of chlorophyll fluorescence of leaves with chemically or genetically
      altered isoprene biosynthesis, that chloroplasts of isoprene-emitting leaves
      dissipate less energy as heat than chloroplasts of non-emitting leaves, when
      exposed to physiologically high temperatures (28-37  degrees C) that do not
      impair the photosynthetic apparatus. The effect was especially remarkable at
      foliar temperatures between 30  degrees C and 35  degrees C, at which isoprene
      emission is maximized and NPQ is quenched by about 20%. Isoprene may also allow
      better stability of photosynthetic membranes and a more efficient electron
      transfer through PSII at physiological temperatures, explaining most of the NPQ
      reduction and the slightly higher photochemical quenching that was also observed
      in isoprene-emitting leaves. The possibility that isoprene emission helps in
      removing thermal energy at the thylakoid level is also put forward, although such
      an effect was calculated to be minimal. These experiments expand current evidence
      that isoprene is an important trait against thermal and oxidative stresses and
      also explains why plants invest resources in isoprene under unstressed
      conditions. By improving PSII efficiency and reducing the need for heat
      dissipation in photosynthetic membranes, isoprene emitters are best fitted to
      physiologically high temperatures and will have an evolutionary advantage when
      adapting to a warming climate. 

PMID- 24676034
TI  - Coupled Intrinsic Connectivity Distribution analysis: a method for exploratory
      connectivity analysis of paired FMRI data.
AB  - We present a novel voxel-based connectivity approach for paired functional
      magnetic resonance imaging (fMRI) data collected under two different conditions
      labeled the Coupled Intrinsic Connectivity Distribution (coupled-ICD). Our
      proposed method jointly models both conditions to incorporate additional paired
      information into the connectivity metric. Voxel-based connectivity holds promise
      as a clinical tool to characterize a wide range of neurological and psychiatric
      diseases, and monitor their treatment. As such, examining paired connectivity
      data such as scans acquired pre- and post-intervention is an important
      application for connectivity methodologically. When presented with data from
      paired conditions, conventional voxel-based methods analyze each condition
      separately. However, summarizing each connection separately can misrepresent
      patterns of changes in connectivity. We show that commonly used methods can
      underestimate functional changes and subsequently introduce and evaluate our
      solution to this problem, the coupled-ICD metric, using two studies: 1) healthy
      controls scanned awake and under anesthesia, and 2) cocaine-dependent subjects
      and healthy controls scanned while being presented with relaxing or drug-related
      imagery cues. The coupled-ICD approach detected differences between paired
      conditions in similar brain regions as the conventional approaches while also
      revealing additional changes in regions not identified using conventional voxel
      based connectivity analyses. Follow-up seed-based analyses on data independent
      from the voxel-based results also showed connectivity differences between
      conditions in regions detected by coupled-ICD. This approach of jointly analyzing
      paired resting-state scans provides a new and important tool with many
      applications for clinical and basic neuroscience research. 

PMID- 24676035
TI  - Bioavailable soil phosphorus decreases with increasing elevation in a subarctic
      tundra landscape.
AB  - Phosphorus (P) is an important macronutrient in arctic and subarctic tundra and
      its bioavailability is regulated by the mineralization of organic P. Temperature
      is likely to be an important control on P bioavailability, although effects may
      differ across contrasting plant communities with different soil properties. We
      used an elevational gradient in northern Sweden that included both heath and
      meadow vegetation types at all elevations to study the effects of temperature,
      soil P sorption capacity and oxalate-extractable aluminium (Alox) and iron (Feox)
      on the concentration of different soil P fractions. We hypothesized that the
      concentration of labile P fractions would decrease with increasing elevation (and
      thus declining temperature), but would be lower in meadow than in heath, given
      that N to P ratios in meadow foliage are higher. As expected, labile P in the
      form of Resin-P declined sharply with elevation for both vegetation types. Meadow
      soils did not have lower concentrations of Resin-P than heath soils, but they did
      have 2-fold and 1.5-fold higher concentrations of NaOH-extractable organic P and
      Residual P, respectively. Further, meadow soils had 3-fold higher concentrations
      of Alox + Feox and a 20% higher P sorption index than did heath soils.
      Additionally, Resin-P expressed as a proportion of total soil P for the meadow
      was on average half that in the heath. Declining Resin-P concentrations with
      elevation were best explained by an associated 2.5-3.0  degrees C decline in
      temperature. In contrast, the lower P availability in meadow relative to heath
      soils may be associated with impaired organic P mineralization, as indicated by a
      higher accumulation of organic P and P sorption capacity. Our results indicate
      that predicted temperature increases in the arctic over the next century may
      influence P availability and biogeochemistry, with consequences for key ecosystem
      processes limited by P, such as primary productivity.

PMID- 24676036
TI  - Contact force and scanning velocity during active roughness perception.
AB  - Haptic perception is bidirectionally related to exploratory movements, which
      means that exploration influences perception, but perception also influences
      exploration. We can optimize or change exploratory movements according to the
      perception and/or the task, consciously or unconsciously. This paper presents a
      psychophysical experiment on active roughness perception to investigate movement
      changes as the haptic task changes. Exerted normal force and scanning velocity
      are measured in different perceptual tasks (discrimination or identification)
      using rough and smooth stimuli. The results show that humans use a greater
      variation in contact force for the smooth stimuli than for the rough stimuli.
      Moreover, they use higher scanning velocities and shorter break times between
      stimuli in the discrimination task than in the identification task. Thus, in
      roughness perception humans spontaneously use different strategies that seem
      effective for the perceptual task and the stimuli. A control task, in which the
      participants just explore the stimuli without any perceptual objective, shows
      that humans use a smaller contact force and a lower scanning velocity for the
      rough stimuli than for the smooth stimuli. Possibly, these strategies are related
      to aversiveness while exploring stimuli. 

PMID- 24676038
TI  - Opportunities for improved chagas disease vector control based on knowledge,
      attitudes and practices of communities in the yucatan peninsula, Mexico.
AB  - BACKGROUND: Chagas disease is a vector-borne parasitic disease of major public
      health importance. Current prevention efforts are based on triatomine vector
      control to reduce transmission to humans. Success of vector control interventions
      depends on their acceptability and value to affected communities. We aimed to
      identify opportunities for and barriers to improved vector control strategies in
      the Yucatan peninsula, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: We employed a
      sequence of qualitative and quantitative research methods to investigate
      knowledge, attitudes and practices surrounding Chagas disease, triatomines and
      vector control in three rural communities. Our combined data show that community
      members are well aware of triatomines and are knowledgeable about their habits.
      However, most have a limited understanding of the transmission dynamics and
      clinical manifestations of Chagas disease. While triatomine control is not a
      priority for community members, they frequently use domestic insecticide products
      including insecticide spray, mosquito coils and plug-in repellents. Families
      spend about $32 US per year on these products. Alternative methods such as yard
      cleaning and window screens are perceived as desirable and potentially more
      effective. Screens are nonetheless described as unaffordable, in spite of a cost
      comparable to the average annual spending on insecticide products.
      CONCLUSION/SIGNIFICANCE: Further education campaigns and possibly financing
      schemes may lead families to redirect their current vector control spending from
      insecticide products to window screens. Also, synergism with mosquito control
      efforts should be further explored to motivate community involvement and ensure
      sustainability of Chagas disease vector control.

PMID- 24676041
TI  - Suppression of target patterns in domain aligned cold-zone annealed block
      copolymer films with immobilized film-spanning nanoparticles.
AB  - We examine the effect of a moving in-plane temperature gradient on the ordering
      of cylinder-forming block-copolymers (BCP) in films containing immobilized
      nanoparticles that span the film thickness. In a previous paper, we reported the
      effect of static step oven-annealing of these films above the glass transition
      temperature Tg for a long period before ordering the BCP film at a much higher
      temperature. In the dynamic film annealing method of the present work, termed
      cold zone annealing (CZA), the material is continuously raised to a temperature
      somewhat above the glass transition temperature and then well above it, with a
      control of the heating time and thermal gradient. Oven annealing before ordering
      has been found to relieve residual stresses in the film associated with large
      thermal expansion of the film upon heating, eliminating the large scale target
      patterns induced by stresses effects associated with residual solvent and thermal
      expansion. By comparison, CZA naturally suppresses undesirable target patterning
      with enhanced ordering kinetics created through this thermal history. 

PMID- 24676037
TI  - Downregulation of immunoglobulin-like transcript-4 (ILT4) in patients with
      psoriatic arthritis.
AB  - OBJECTIVE: The immunoglobulin-like transcript-4 (ILT4) is an inhibitory receptor
      that modulates the activity of innate immune agents. We determined the expression
      of ILT4 and analysed the relationship with the expression of costimulatory
      proteins and tumor necrosis factor-alpha (TNF-alpha) production in monocytes from
      patients with psoriatic arthritis (PsA) starting anti-TNF treatment. METHODS:
      Peripheral blood monocytes from 15 healthy controls and from 16 patients with PsA
      were activated in vitro by CD40 ligand (CD40L) and analyzed for ILT4, CD40, CD80
      and CD86 expression, and spontaneous lipopolysaccharide (LPS)-induced TNF-alpha
      production by flow cytometry, before and after treatment with adalimumab.
      RESULTS: The percentage of ILT4-negative monocytes was greater in PsA patients
      compared to controls and negatively correlated with DAS44. Normal monocytes
      treated with sera of PsA patients showed a reduced expression of ILT4 compared
      with monocytes exposed to sera from controls. CD40, CD80 and CD86 expression was
      higher in patients compared to controls. Both spontaneous and LPS-induced TNF
      alpha production was restricted to ILT4-negative monocytes and was greater in PsA
      patients compared to controls. Finally, twelve weeks-treatment with adalimumab
      resulted in a significant increase of ILT4 expression and a decrease of
      costimulatory molecules expression in PsA patients, compared to pre-therapy
      levels. CONCLUSIONS: These data support the possibility that changes in the
      immunophenotype of monocytes play a role in the pathogenesis of PSA. Thus,
      modulation of the expression of ILT4 may represent an enticing new therapeutic
      target.

PMID- 24676042
TI  - First- and last-year medical students: is there a difference in the prevalence
      and intensity of anxiety and depressive symptoms?
AB  - OBJECTIVE: Medical training is considered a significant stress factor. We sought
      to assess the prevalence and intensity of anxiety and depressive symptoms in
      medical students and compare samples of first-year and sixth-year students.
      METHOD: This was a cross-sectional study of first- and sixth-year medical
      students who attended classes regularly. The study instruments were a
      sociodemographic questionnaire, the Beck Depression Inventory (BDI), and the Beck
      Anxiety Inventory (BAI). RESULTS: A total of 232 students (110 first-year, 122
      sixth-year) completed the questionnaires, for a response rate of 67.4%. Overall
      50.4% of respondents were male (56.4% of first-year and 45.1% of sixth-year
      students). Anxiety symptoms were reported by 30.8% of first-year students and
      9.4% of sixth-year students (p < 0.001). Female students were more affected by
      anxiety. There were no significant between-group differences in depressive
      symptoms. CONCLUSION: A higher prevalence of anxiety symptoms was found in first
      year medical students as compared with sixth-year students. Strategies should be
      developed to help medical students, particularly female students, manage these
      symptoms at the beginning of their medical training.

PMID- 24676043
TI  - Comorbid psychiatric disorders and stages of change in cannabis-dependent,
      treatment-seeking patients.
AB  - OBJECTIVES: To determine whether and to what extent cannabis dependence is
      associated with comorbid psychiatric disorders and specific stages of change in
      treatment-seeking patients. METHODS: We evaluated 80 cannabis-dependent,
      treatment-seeking patients residing in an urban area. Data on cannabis
      dependence, psychiatric disorders, and motivation were obtained using the
      Schedules for Clinical Assessment in Neuropsychiatry and the University of Rhode
      Island Change Assessment (URICA). RESULTS: A diagnosis of schizophrenia was found
      to correlate with lower motivation scores (p = 0.038), which could have a
      negative effect on adherence to treatment. CONCLUSION: The high prevalence of
      concurrent psychiatric disorders in cannabis-dependent patients should serve as a
      stimulus for early screening and treatment of such disorders. Health care
      professionals should be aware of the magnitude of this association to increase
      the level of motivation in cannabis-dependent patients with severe concurrent
      psychiatric disorders.

PMID- 24676044
TI  - Use of psychotropic medications during pregnancy: perception of teratogenic risk
      among physicians in two Latin American countries.
AB  - OBJECTIVE: Pregnant women and their health care professionals commonly believe
      that use of medications during pregnancy may be harmful to the unborn fetus. The
      objective of this study was to evaluate the risk perception of psychotropic drug
      use in pregnancy among physicians in different medical specialties. METHOD: This
      was a convenience survey conducted at outpatient clinics in the cities of Recife,
      Brazil, and La Plata, Bahia Blanca, and Buenos Aires, Argentina. Physicians who
      agreed to participate were asked to rate their perception of teratogenic risk
      among different classes of drugs, which included antidepressants, antipsychotics,
      anticonvulsants, and benzodiazepines. RESULTS: Two hundred and thirty-eight
      physicians completed the survey (response rate, 98%). These included
      psychiatrists, obstetricians, neurologists, cardiologists, gastroenterologists,
      and general practitioners. Among different specialties, a minority of
      psychiatrists perceived psychotropic drugs to be highly teratogenic
      (antidepressants, 12.5%; antipsychotics, 15%; benzodiazepines, 25%) as compared
      with other specialties (p < 0.003 for each drug class). There was no difference
      in perceived risk of antiepileptic drugs among specialties, including
      psychiatrists. CONCLUSION: The risk associated with use of psychotropic drugs in
      pregnancy was overestimated by physicians of all medical specialties, except
      psychiatry. All physicians should be aware of the safety/risk of psychotropic
      agents in pregnancy, as they may be required to give advice and/or prescribe
      these drugs to pregnant women.

PMID- 24676045
TI  - Factors associated with recurrence of alcohol-related traffic violations in
      southern Brazil.
AB  - OBJECTIVE: To analyze variables associated with recurrence of blood alcohol
      content (BAC)-related traffic violations among drivers in southern Brazil.
      METHOD: This cross-sectional study included 12,204 driving-under-the-influence
      (DUI) offenders according to data provided by the Rio Grande do Sul state
      Transportation Department. Sociodemographic characteristics, license duration,
      license category, and psychological assessment results were analyzed. Drivers
      convicted of DUI more than once in 2009/2010 were considered recidivists.
      Variables were evaluated using descriptive statistical analysis and Poisson
      regression, adjusted by sex, age, and education level. RESULTS: A total of 538
      (4.41%) drivers were considered recidivists. The following variables showed the
      strongest associations with recidivism: being aged 41-50 years (prevalence ratio
      [PR] = 3.41), being licensed for >= 12 years (PR = 1.86), being licensed for
      motorcycles, cars and trucks (PR = 1.36), having a license with psychological
      restrictions (PR = 1.33), and driving a truck or a similar vehicle at the moment
      of notification (PR = 1.08). CONCLUSIONS: In the age group with the highest risk
      for recurrence, drivers showed a higher probability of having a diagnosis of
      alcohol dependence and other psychiatric comorbidities that hinder the control of
      alcohol use. Psychological assessments seem to be important in predicting repeat
      offenses, especially when limited aptitudes are suspected, and should therefore
      be better investigated.

PMID- 24676048
TI  - Psychopathic traits in young offenders vs. non-offenders in similar socioeconomic
      condition.
AB  - OBJECTIVE: To analyze the differences in psychopathic traits between offender and
      non-offender youths with similar socioeconomic backgrounds. METHOD: The
      Psychopathy Checklist Revised (PCL-R) scale was used to identify whether 39 young
      offenders with no history of mental disorders or criteria for psychopathy
      exhibited differences in its total score, and specifically for factor 1 or factor
      2 of this scale, when compared with 32 other young people, living in similar
      socioeconomic conditions, who had not committed offenses. RESULTS: We observed
      statistically significant between-group differences (p < 0.01) in mean PCL-R
      scores, with a mean score of 13.4 in the offender group vs. 2.1 in the non
      offender group. We also detected significant between-group differences when we
      analyzed mean factor 1 (p < 0.01) and factor 2 (p < 0.01) scores separately.
      Although the groups exhibited statistically significant difference in educational
      attainment, between-group comparison of mean PCL-R scores controlling for
      educational attainment by analysis of covariance (ANCOVA) showed that the
      difference in PCL-R scores remained statistically significant (p < 0.01).
      CONCLUSIONS: We conclude that, in this sample, the presence of both primary
      (interpersonal/affective characteristics) and secondary (lifestyle/antisocial
      behavior) psychopathic traits differed between offender and non-offender youths,
      even when excluding psychopathy and other mental disorders from the assessments.
      These results suggest a need for wide-ranging interventions, not restricted to
      socioeconomic aspects, for the management of juvenile delinquency.

PMID- 24676046
TI  - Sensorimotor performance in euthymic bipolar disorder: the MPraxis (PennCNP)
      analysis.
AB  - BACKGROUND: Sensorimotor deficits are an important phenomenological facet
      observed in patients with bipolar disorder (BD). However, there is little
      research on this topic. We hypothesize that the MPraxis test can be used to
      screen for motor impairments in BD aiming movements. METHOD: The MPraxis, which
      is a quick and easy-to-apply computerized test, measures sensorimotor control.
      During the test, the participant must move the computer mouse cursor over an ever
      shrinking green box and click on it once. We predict that the MPraxis test is
      capable of detecting differences in sensorimotor performance between patients
      with BD and controls. We assessed 21 euthymic type I BD patients, without DSM-IV
      TR Axis I comorbidity, and 21 healthy controls. RESULTS AND CONCLUSIONS: Compared
      to the controls, the patients with BD presented a lower response time in their
      movements in all conditions. Our results showed sensorimotor deficits in BD and
      suggested that the MPraxis test can be used to screen for motor impairments in
      patients with euthymic BD.

PMID- 24676047
TI  - Systematic review of N-acetylcysteine in the treatment of addictions.
AB  - OBJECTIVE: To conduct the first systematic literature review of clinical trials
      of N-acetylcysteine (NAC) for the treatment of substance abuse disorders and
      addictive behaviors. METHODS: A search of the MEDLINE, Embase and PsycINFO
      databases was conducted. The inclusion criteria for the review were clinical
      trials that used NAC in the treatment of a disorder related to substance use
      and/or addictive behaviors, limited to texts in English, Spanish, or French. The
      selected studies were evaluated with respect to type of trial, sample size,
      diagnostic input, intervention, length of follow-up, outcome variables, and
      results. RESULTS: Nine studies analyzing a total of 165 patients met the
      eligibility criteria and were included in qualitative analysis. These studies
      evaluated the role of NAC in cocaine dependence (three studies), cannabis
      dependence (two studies), nicotine dependence (two studies), methamphetamine
      addiction (one study), and pathological gambling (one study). Five of these
      trials were double-blind, randomized, and placebo-controlled. CONCLUSIONS: The
      studies analyzed suggest a potential role for NAC in the treatment of addiction,
      especially of cocaine and cannabis dependence. These results are concordant with
      the hypothesis of the involvement of glutamatergic pathways in the
      pathophysiology of addiction.

PMID- 24676049
TI  - Fluvoxamine alters the activity of energy metabolism enzymes in the brain.
AB  - OBJECTIVE: Several studies support the hypothesis that metabolism impairment is
      involved in the pathophysiology of depression and that some antidepressants act
      by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs
      cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the
      brain of rats subjected to prolonged administration of fluvoxamine. METHODS:
      Wistar rats received daily administration of fluvoxamine in saline (10, 30, and
      60 mg/kg) for 14 days. Twelve hours after the last administration, rats were
      killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus,
      striatum, and cerebellum were rapidly isolated. RESULTS: The activities of
      citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were
      decreased after prolonged administration of fluvoxamine in rats. However, the
      activities of complex II, succinate dehydrogenase, and creatine kinase were
      increased. CONCLUSIONS: Alterations in activity of energy metabolism enzymes were
      observed in most brain areas analyzed. Thus, we suggest that the decrease in
      citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be
      related to adverse effects of pharmacotherapy, but long-term molecular
      adaptations cannot be ruled out. In addition, we demonstrated that these changes
      varied according to brain structure or biochemical analysis and were not dose
      dependent.

PMID- 24676050
TI  - Role of interface coupling inhomogeneity in domain evolution in exchange bias.
AB  - Models of exchange-bias in thin films have been able to describe various aspects
      of this technologically relevant effect. Through appropriate choices of free
      parameters the modelled hysteresis loops adequately match experiment, and typical
      domain structures can be simulated. However, the use of these parameters, notably
      the coupling strength between the systems' ferromagnetic (F) and
      antiferromagnetic (AF) layers, obscures conclusions about their influence on the
      magnetization reversal processes. Here we develop a 2D phase-field model of the
      magnetization process in exchange-biased CoO/(Co/Pt)*n that incorporates the 10
      nm-resolved measured local biasing characteristics of the antiferromagnet. Just
      three interrelated parameters set to measured physical quantities of the
      ferromagnet and the measured density of uncompensated spins thus suffice to match
      the experiment in microscopic and macroscopic detail. We use the model to study
      changes in bias and coercivity caused by different distributions of pinned
      uncompensated spins of the antiferromagnet, in application-relevant situations
      where domain wall motion dominates the ferromagnetic reversal. We show the excess
      coercivity can arise solely from inhomogeneity in the density of biasing- and
      anti-biasing pinned uncompensated spins in the antiferromagnet. Counter to
      conventional wisdom, irreversible processes in the latter are not essential. 

PMID- 24676051
TI  - Angiolymphoid hyperplasia with eosinophilia of the orbit and ocular adnexa:
      report of 5 cases.
AB  - IMPORTANCE: To report the clinical and histopathologic findings of ocular adnexal
      angiolymphoid hyperplasia with eosinophilia, an unusual but often misdiagnosed
      benign disorder. OBSERVATIONS: The ophthalmologic findings of angiolymphoid
      hyperplasia with eosinophilia with ocular adnexal involvement are variable and
      include eyelid swelling, ptosis, proptosis, and loss of vision. Imaging studies
      typically reveal a well-circumscribed mass in the orbit. The condition may
      resemble other diseases that involve the orbit and ocular adnexal tissue, such as
      lymphoma, hemangioma, sarcoidosis, and dermoid cyst. Histopathologic analysis
      reveals marked vascular proliferation with an accompanying inflammation composed
      of numerous eosinophils, lymphocytes, and plasma cells. CONCLUSIONS AND
      RELEVANCE: Angiolymphoid hyperplasia with eosinophilia is a rare disease that can
      affect the ocular adnexal tissue. The clinical presentation is often nonspecific;
      therefore, histopathologic studies are essential for diagnosis and subsequent
      management of this benign condition.

PMID- 24676052
TI  - Comparative analysis of the macroscale structural connectivity in the macaque and
      human brain.
AB  - The macaque brain serves as a model for the human brain, but its suitability is
      challenged by unique human features, including connectivity reconfigurations,
      which emerged during primate evolution. We perform a quantitative comparative
      analysis of the whole brain macroscale structural connectivity of the two
      species. Our findings suggest that the human and macaque brain as a whole are
      similarly wired. A region-wise analysis reveals many interspecies similarities of
      connectivity patterns, but also lack thereof, primarily involving cingulate
      regions. We unravel a common structural backbone in both species involving a
      highly overlapping set of regions. This structural backbone, important for
      mediating information across the brain, seems to constitute a feature of the
      primate brain persevering evolution. Our findings illustrate novel evolutionary
      aspects at the macroscale connectivity level and offer a quantitative
      translational bridge between macaque and human research. 

PMID- 24676053
TI  - Fish functional traits correlated with environmental variables in a temperate
      biodiversity hotspot.
AB  - The global biodiversity crisis has invigorated the search for generalized
      patterns in most disciplines within the natural sciences. Studies based on
      organismal functional traits attempt to broaden implications of results by
      identifying the response of functional traits, instead of taxonomic units, to
      environmental variables. Determining the functional trait responses enables more
      direct comparisons with, or predictions for, communities of different taxonomic
      composition. The North American freshwater fish fauna is both diverse and
      increasingly imperiled through human mediated disturbances, including climate
      change. The Tennessee River, USA, contains one of the most diverse assemblages of
      freshwater fish in North America and has more imperiled species than other
      rivers, but there has been no trait-based study of community structure in the
      system. We identified 211 localities in the upper Tennessee River that were
      sampled by the Tennessee Valley Authority between 2009 and 2011 and compiled fish
      functional traits for the observed species and environmental variables for each
      locality. Using fourth corner analysis, we identified significant correlations
      between many fish functional traits and environmental variables. Functional
      traits associated with an opportunistic life history strategy were correlated
      with localities subject to greater land use disturbance and less flow regulation,
      while functional traits associated with a periodic life history strategy were
      correlated with localities subject to regular disturbance and regulated flow.
      These are patterns observed at the continental scale, highlighting the
      generalizability of trait-based methods. Contrary to studies that found no
      community structure differences when considering riparian buffer zones, we found
      that fish functional traits were correlated with different environmental
      variables between analyses with buffer zones vs. entire catchment area land cover
      proportions. Using existing databases and fourth corner analysis, our results
      support the broad application potential for trait-based methods and indicate
      trait-based methods can detect environmental filtering by riparian zone land
      cover. 

PMID- 24676054
TI  - Construction of a SSR-based genetic map and identification of QTLs for catechins
      content in tea plant (Camellia sinensis).
AB  - Catechins are the most important bioactive compounds in tea, and have been
      demonstrated to possess a wide variety of pharmacological activities. To
      characterize quantitative trait loci (QTLs) for catechins content in the tender
      shoots of tea plant, we constructed a moderately saturated genetic map using 406
      simple sequence repeat (SSR) markers, based on a pseudo-testcross population of
      183 individuals derived from an intraspecific cross of two Camellia sinensis
      varieties with diverse catechins composition. The map consisted of fifteen
      linkage groups (LGs), corresponding to the haploid chromosome number of tea plant
      (2n = 2x = 30). The total map length was 1,143.5 cM, with an average locus
      spacing of 2.9 cM. A total of 25 QTLs associated with catechins content were
      identified over two measurement years. Of these, nine stable QTLs were validated
      across years, and clustered into four main chromosome regions on LG03, LG11, LG12
      and LG15. The population variability explained by each QTL was predominantly at
      moderate-to-high levels and ranged from 2.4% to 71.0%, with an average of 17.7%.
      The total number of QTL for each trait varied from four to eight, while the total
      population variability explained by all QTLs for a trait ranged between 38.4% and
      79.7%. This is the first report on the identification of QTL for catechins
      content in tea plant. The results of this study provide a foundation for further
      cloning and functional characterization of catechin QTLs for utilization in
      improvement of tea plant.

PMID- 24676056
TI  - Stabilizing chromophore binding on TiO2 for long-term stability of dye-sensitized
      solar cells using multicomponent atomic layer deposition.
AB  - Ambient humidity and high temperature are known to degrade dye-sensitized solar
      cells (DSSCs) via chromophore desorption. Recently, enhanced dye-attachment to
      TiO2 surfaces has been realized by coating molecularly functionalized surfaces
      with inorganic atomic layer deposition (ALD) coatings. Here, we apply this ALD
      approach to DSSCs and demonstrate that high energy conversion efficiencies can be
      maintained while significantly extending device lifetimes. While single component
      ALD layers show improved high-temperature stability, it significantly degraded up
      to 45% of initial DSSC performance right after ALD. We, however, find that mixed
      component ALD layers provide initial efficiencies within 90% of their untreated
      counterparts while still extending device lifetimes. Optimized ALD protection
      schemes maintain 80% of their initial efficiency after 500 h of thermal aging at
      80  degrees C whereas efficiency of DSSCs with no ALD protection drop below 60%
      of their initial efficiencies. IR spectroscopy conducted in situ during ALD
      reveals that carboxylate linker groups transition from unbound or weakly-bound
      states, respectively, to more strongly bound bidentate structures. This strategy
      to improve dye-attachment by ALD while maintaining high performance is novel and
      promising for extending the functional lifetime for DSSCs and other related
      devices. 

PMID- 24676055
TI  - FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster
      epithelia and human cancer cells.
AB  - Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate
      multiple signalling pathways, including mitogen-activated protein (MAP) kinase
      pathway. FAK interacts with several RTKs but little is known about how FAK
      regulates their downstream signalling. Here we investigated how FAK regulates
      signalling resulting from the overexpression of the RTKs RET and EGFR. FAK
      suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK
      pathway. This regulation was also observed in MDA-MB-231 human breast cancer
      cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK
      reduced receptor recycling into the plasma membrane, which resulted in lower MAPK
      activation. Conversely, increasing the membrane pool of the receptor increased
      MAPK pathway signalling. FAK is widely considered as a therapeutic target in
      cancer biology; however, it also has tumour suppressor properties in some
      contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling
      described here may have potential implications in the designing of therapy
      strategies for RTK-driven tumours. 

PMID- 24676058
TI  - Is income inequality 'toxic for mental health'? An ecological study on municipal
      level risk factors for depression.
AB  - Most inequality research on the relationship between inequality and mental health
      has focused on cross-country variation. Findings from within-country data are
      mixed. We examined whether changes in municipal Gini index or in the share of
      people living in relative poverty were linked to changes in the use of
      antidepressants in several Finnish municipalities between 1995 and 2010. We found
      that more young adult females used antidepressants in municipalities where
      relative poverty had increased. Changes in municipal-level Gini index were not
      positively associated with changes in the use of antidepressants in the
      municipalities between 1995 and 2010. However, fewer elderly females used
      antidepressants in municipalities where the Gini index increased. In addition,
      more young adults used antidepressants in municipalities where the number of
      those not being educated or trained had also increased. An increase in the number
      of persons over 65 years of age living alone was positively associated with an
      increase in the use of antidepressants among elderly females. 

PMID- 24676059
TI  - U4 at the 3' UTR of PB1 segment of H5N1 influenza virus promotes RNA polymerase
      activity and contributes to viral pathogenicity.
AB  - The viral RNA-dependent RNA polymerase has been found to contribute to efficient
      replication in mammalian systems and to the high pathogenicity of H5N1 influenza
      A virus in humans and other mammals. The terminal untranslated regions of the
      viral segments perform functions such as polyadenylation and contain signals for
      genomic packaging and initiation of RNA synthesis. These sequences are highly
      conserved, apart from a U/C polymorphism at position 4 of the 3' end, most often
      seen in the polymerase gene segments. However, no study has yet tested whether
      the untranslated regions of H5N1 make any contribution to its high pathogenicity.
      Herein, the association of the fourth nucleotide at the 3' end of the
      untranslated region in segment 2 (PB1), of A/Vietnam/1194/2004 (H5N1), with
      pathogenicity was examined in mice. To this end, an RNA polymerase reporter
      system was constructed, and viruses with mutations at this site were rescued.
      Results showed the U4 in PB1 was found to contribute to greater amounts of RNA
      dependent RNA polymerase activity and differentially regulate genomic
      transcription and replication. Although a recombinant H5N1 virus with the rarer
      C4 sequence in all eight segments was viable and replicated to high titers in
      vitro, replacing a single U4 at the 3' termini of the PB1 gene segment enhanced
      viral reproduction and more pathogenesis. In this way, these data showed the
      importance of untranslated regions of H5N1 influenza virus to pathogenicity. 

PMID- 24676061
TI  - Recent advances in the synthesis of pyrroles by multicomponent reactions.
AB  - Pyrrole is one of the most important one-ring heterocycles. The ready
      availability of suitably substituted and functionalized pyrrole derivatives is
      essential for the progress of many branches of science, including biology and
      materials science. Access to this key heterocycle by multicomponent routes is
      particularly attractive in terms of synthetic efficiency, and also from the
      environmental point of view. We update here our previous review on this topic by
      describing the progress made in this area in the period between mid-2009 and the
      end of 2013. 

PMID- 24676062
TI  - [Broadening the participation and strengthening the unity].

PMID- 24676060
TI  - Artificial language training reveals the neural substrates underlying addressed
      and assembled phonologies.
AB  - Although behavioral and neuropsychological studies have suggested two distinct
      routes of phonological access, their neural substrates have not been clearly
      elucidated. Here, we designed an artificial language (based on Korean Hangul)
      that can be read either through addressed (i.e., whole word mapping) or assembled
      (i.e., grapheme-to-phoneme mapping) phonology. Two matched groups of native
      English-speaking participants were trained in one of the two conditions, one hour
      per day for eight days. Behavioral results showed that both groups correctly
      named more than 90% of the trained words after training. At the neural level, we
      found a clear dissociation of the neural pathways for addressed and assembled
      phonologies: There was greater involvement of the anterior cingulate cortex,
      posterior cingulate cortex, right orbital frontal cortex, angular gyrus and
      middle temporal gyrus for addressed phonology, but stronger activation in the
      left precentral gyrus/inferior frontal gyrus and supramarginal gyrus for
      assembled phonology. Furthermore, we found evidence supporting the strategy-shift
      hypothesis, which postulates that, with practice, reading strategy shifts from
      assembled to addressed phonology. Specifically, compared to untrained words,
      trained words in the assembled phonology group showed stronger activation in the
      addressed phonology network and less activation in the assembled phonology
      network. Our results provide clear brain-imaging evidence for the dual-route
      models of reading. 

PMID- 24676063
TI  - [Health education in pregnancy and postpartum: meanings attributed by puerperal
      women].
AB  - Descriptive study, qualitative, that aimed to capture the content of social
      representations of puerperal women on health education in pregnancy and
      postpartum in primary health care. Users were 31 Family Health Centers in
      Fortaleza, Ceara, over 18 years in the postpartum period, with at least six
      visits to prenatal and one postpartum consultation. It was held a lexical
      analysis of data from semi-structured interviews with the software ALCESTE. The
      representations of puerperal women on health education are linked to
      institutional educational practices, with emphasis on lectures, family and school
      education, and community education. It predominate the traditional pedagogy, with
      the transmission of information, punctual and widespread. It is necessary to
      change the pedagogical logic, expanding educational groups with knowledge
      sharing. 

PMID- 24676064
TI  - [Breastfeeding difficulties and influence in the early weaning].
AB  - The study aimed to verify the average time of exclusive breastfeeding (AME) of
      infants born at Baby-Friendly Hospital Initiative (BFHI) and to associate it with
      the following variables: marital status, mother's age, infant's weight,
      difficulties found and instructions received. This is a cohort study with a
      sample of 225 mothers interviewed postpartum and on the 15th, 30th, 60th, 120th
      and 180th days after discharge, by telephone. The monitoring of AME showed median
      of 113 days and 34,1% of the mothers kept it for up 180 days. There was a
      significant statistical correlation between the time of AME and difficulties
      found. There was no significant statistical correlation between time of AME and
      the variables: marital status, mother's age, infant's weight and instructions
      received. This research showed increased weaning at 60 days in women who have had
      difficulty in pre-discharge. The study showed the positive influence of the BFHI
      in adherence of mothers to the AME. 

PMID- 24676065
TI  - [Children and adolescents with cancer under palliative care: experience of family
      members].
AB  - This study's objective was to investigate the experience of family members of
      children and adolescents with cancer in terms of palliative care, especially the
      care provided in the final stage of life. This is a descriptive and exploratory
      study with qualitative data analysis. A total of 14 family members participated
      in the study. They were the caregivers of children and adolescents with cancer
      who died, and were followed up by a teaching hospital in the state of Sao Paulo.
      Empirical data were organized around three themes: "The impact of the worsening
      of the disease on the family's dynamics", "Communicating bad news" and "The
      experience of the family concerning palliative care". This study is relevant to
      children and adolescents with cancer in the end-of life care because the complex,
      dynamics, and comprehensive experiences of families in the care of children and
      adolescents in this period can contribute to better understanding of the process
      of providing care in light of the fundamentals of palliative care. 

PMID- 24676066
TI  - [Route taken by families of children hospitalized in a teaching hospital].
AB  - Exploratory and descriptive study, of qualitative nature, developed with the
      purpose of knowing the route of the child's family admitted to the hospital. The
      data were collected at the pediatric unit of the Regional University Hospital of
      Maringa (HUM), through semi-structured interviews with the accompanying family
      members. After analysis of content, two categories emerged: the role of the
      family in the identification of deviations in the child's health, and the
      (un)readiness of the health services: impacts on the child health attendance. The
      study evidenced an expectation of the family in face of the child's illness,
      searching for alternative strategies and late seeking for health services. These,
      in turn, show gaps along the attendance process, from diagnosis to treatment,
      thus raising familiar stress and increasing the possibilities of aggravation of
      the clinical condition of the child. 

PMID- 24676067
TI  - [Insulin resistance in adolescents with and without overweight of a municipality
      of Great Florianopolis-SC].
AB  - Increased overweight prevalence among adolescents is linked to Diabetes mellitus
      type 2 and insulin resistance (IR). This study aimed to compare insulin
      resistance among adolescents with normal weight and overweight. The subjects of
      the study were 96 adolescents (35.4 % male, 50% overweight) aged 14-19 years
      (16.6+/-0.98). The BMI and waist circumference (WC) were categorized according to
      the literature. For IR, the HOMA-IR cutoff of 4,39 was used. The chi-square test
      evaluated the prevalence difference between categories of weight and WC (p
      <0.05). There were no significant differences among categories and IR prevalence
      was 2.1%. However, overweight adolescents tended to have higher values of HOMA
      IR. According to glycaemia criteria, IR was not observed in the sample. 

PMID- 24676069
TI  - [Chronic pain related to AIDS: perspective of nurses and doctors].
AB  - The objective was to identify the features and the management of chronic pain
      associated to Acquired Immunodeficiency Syndrome (AIDS) from the perspective of
      nurses and doctors. Qualitative study conducted at a reference hospital in
      Fortaleza- CE, Brazil, with 20 professionals. It was applied semi-structured
      interview and the speeches were analyzed using content analysis of Bardin,
      emerging three categories: Characterization of pain, Clinical evaluation of pain
      and Clinical care of pain. It was found that pain in AIDS manifests itself as
      persistent, disabling, with difficult control, and its management based on
      accurate identification of the causal factors and on implementation of
      pharmacological and non pharmacological treatment offered by the
      interdisciplinary team. The study provides relevant data on pain in AIDS
      patients, demonstrating the need to rethink the model of care management
      interventions to promote greater efficacy of analgesia and to improve
      interdisciplinary approach to pain for better pain evaluation and treatment. 

PMID- 24676068
TI  - [Knowledge and attitudes of a public school's adolescents on sexual transmission
      of HIV].
AB  - The research objectives were to describe the knowledge about the transmission of
      HIV/AIDS, analyze the sexual behavior and attitudes towards condom use among
      adolescents. Exploratory survey conducted in 2009 with 234 students of a school
      in Fortaleza, Brazil. We used semi - structured questionnaire and Likert Scale.
      The results showed that 46.6% of the sample have already initiated sexual life,
      40.7% and 29.5% did not use condoms at the first or last intercourse,
      respectively, due to various reasons like not having a condom at the time
      (27.3%), use of contraceptive pill (15.2%) and trust in their partner (15.2%).
      These teenagers have questions about HIV transmission. Women were more favorable
      to condom use than men. One conclude that early initiation of sexual life, doubts
      about HIV transmission and ineffective condom use are factors that make young
      people's vulnerability. 

PMID- 24676070
TI  - [Implementation of the nursing process to a crack user based on Betty Neuman
      model].
AB  - The objective was to propose a care strategy for crack users, through
      implementation of the nursing process. This is a case study, descriptive and
      exploratory with qualitative approach based on Neuman and the NANDA-NIC-NOC.
      Scenario: Psychosocial Care Center - Alcohol and Drugs from Vitoria-ES. We
      applied the standard questionnaire of crack consumption, Addiction Severity
      Index, Mini International Neuropsychiatric Interview and Parental Bonding
      Instrument. It was found the complexity that lining the intra, inter and extra
      personal stressful situations. We discussed three diagnoses: 'poor knowledge
      about the substance use control ', 'ineffective coping' and 'social isolation',
      and interventions were suggested by articulation between NIC, NOC and secondary
      prevention of Neuman. It is therefore an important function of the nurse to
      mobilize system resources - internal and external - for stabilization and
      conservation of energy, in order to strengthen the lines of resistance, in
      addition to considering all the variables of the system and not only the use of
      crack. 

PMID- 24676071
TI  - [Meanings of social support for people submitted to coronary artery by-pass graft
      surgery: ethnographic study].
AB  - The aim of this ethnographic study was to understand the meanings of social
      support according to a group of people submitted to coronary artery bypass graft
      surgery. Semi structured interview and direct observations were the techniques
      used for data collection, which took place at the participants' homes and during
      outpatient return appointments. Data were collected between April/2010 and
      April/2011, involving eleven individuals, mostly married, between 49 and 73 years
      of age. The main reported source of support came from relatives. Religious
      support was another type mentioned, considered fundamental when making decisions
      about the surgery. The meaning of support was related to direct help from
      relatives, concerning instrumental (accomplishment of domestic and self-care
      activities) as well as emotional and religious help (focus on coping with the
      disease and surgery and explanations for the disease and surgery as a moment of
      threat and rupture). 

PMID- 24676072
TI  - [Biosafety in the perspective of nursing staff of Intensive Care Units].
AB  - This is a descriptive study with a qualitative approach that aimed to investigate
      the knowledge and practices of the nursing staff about biosafety in Intensive
      Care Units, and identify biohazard situations to which the worker is exposed, and
      the units' adherence to standard Regulating no 32. Data collection was done
      through interviews and observation, in the first half of 2012, and the processing
      of data was done through thematic analysis. This study showed partial adherence
      to biosafety standards by institutions and professionals surveyed and deficiency
      of discussions on the topic in the spaces of continuing education. The promotion
      of initiatives for education of safe practices and the update was established as
      promoter of health and the prevention of legal exposures by health infractions so
      configured. 

PMID- 24676073
TI  - [Prevalence and clinical significance of interactions drug-enteral nutrition in
      Intensive Care Units].
AB  - This is a multicenter, cross-sectional retrospective study, which aimed to
      determine the prevalence of interactions drug-enteral nutrition (EN) in Intensive
      Care Units (ICU) of seven teaching hospitals in Brazil, and to analyze the
      clinical significance of them. Information on medications and EN administered
      with 24 hours and 120 hours of hospitalization were collected. For identification
      of drug-EN interaction was employed software Drug Reax(r). It was investigated
      1.124 records. Of these, 320 patients, with 24 hours of hospitalization, were on
      EN, and 20 (6.3%) had drug-EN interaction. Of the 504 patients with 120 hours of
      hospitalization, 39 (7.7%) had drug-EN interaction. The most frequent drug-EN
      interactions of clinical significance were phenytoin-EN, warfarin-EN and
      levothyroxine-EN. Drug-EN interactions may interfere with the quality and cost
      effectiveness of care in ICU, so it is essential that the health team has
      knowledge about them. 

PMID- 24676074
TI  - [Ecosystemic and gerontotechnological actions in complex nursing care to the
      elderly with ostomy].
AB  - The goal was to identify the ecosystem and gerontogeriatric technological actions
      to be done in a complex nursing care for the elderly patients of ostomy. To do
      so, a qualitative and descriptive research was made on a Case Study. The data
      were collected through interviews. The elderly were classified due to the
      Functioning, Disability and Health. They also went through physical exams and
      systematic observation. Ten people from the Estomatherapy Service of the south of
      Brazil took part in the research along the period of June to August of 2012. A
      theoretical model was developed and the data were compared with a protocol. The
      ecosystem actions identified the construction of a therapeutic environment, the
      guaranty of physical access and environmental adaptation. The gerontogeriatric
      technological actions identified a health educative process, the routing to the
      support group and the material and necessary equipment distribution for self
      care. Being the nursing care primordial for the elderly patients of ostomy, they
      are able to face their limitations, demystifying their deficiency/ disability
      /health. 

PMID- 24676075
TI  - [From violence to bonding: constructing new meanings for attention to the
      crisis].
AB  - This study aimed to know the meanings present in the discursive practices of the
      Centers for Psychosocial Care's professionals, produced by new ways to cope and
      relate to the subject in severe psychological crisis. This is a qualitative
      research, based on the theoretical perspective of social constructionism. It was
      analyzed 27 interviews of professionals from the identification of interpretative
      repertoires and construction of Association of Ideas Maps. Data were organized
      into themes: Difficulties of contention in service; Senses built around this
      practice; Professionals placements regarding that practice; Participation of the
      Military Police in the care of the crisis; Sense of responsibility of the nursing
      staff in caring for the crisis. It was demonstrated the need for discussion and
      construction of crisis care practices that are more collective and contract based
      on solid relationships that respect the uniqueness and subjectivity of the
      subject. 

PMID- 24676076
TI  - [Embracement: when the user knocks on the door].
AB  - Qualitative study conducted between April and June 2010, in a health-care teacher
      who works in the Family Health Strategy, located in Salvador -Bahia, the study
      aimed to analyze the perceptions of users about the embracement. Study
      participants were 12 subjects of both sexes. The data were submitted to
      categorical analysis, from which emerged four categories: User understanding on
      embracement; Relationship between the health team and embracement; Embracement as
      part of accountability, co-responsibility and problem solving; Barriers to
      embracement. The analysis and discussion of the above categories suggests that
      the embracement is a proposal on continuous improvement even when there is an
      effort to achieve them in health practices coming in the intersubjectivity of the
      subjects involved. 

PMID- 24676077
TI  - [Technology in nursing care: an analysis from the conceptual framework of
      Fundamental Nursing].
AB  - This is a qualitative, field research, whose purpose was to discuss the use of
      technologies in the nursing care in intensive therapy, taking as reference the
      theoretical conceptual framework of Fundamental Nursing. Observation and
      interviews were conducted with twenty two nurses of an intensive therapy unit,
      with ethnographic analysis. The technology, from the domain of a technological
      language, provides conditions so that the fundamentals of the nursing care can be
      effectively incorporated to the nurse practice. The idea of dehumanization linked
      to the technology can be explained by the way that the nurse ads sense to the
      things related to his daily life, which will guide his action. The conclusion is
      that the technologies help to promote life and to rescue the human. 

PMID- 24676078
TI  - [Work accidents with biological material occurred in municipalities of Minas
      Gerais].
AB  - The study aimed to identify the profile accidents involving exposure to
      biological material occurring in Minas Gerais. A descriptive study carried out by
      querying the Information System for Notifiable Diseases, 50 cities in south of
      Minas Gerais State, Brazil, in the period of 2007-2011. Were recorded 460
      accidents, and about half occurred among nursing assistants and technicians,
      followed by nurses and physicians. There were more accidents due to improper
      disposal of sharps. Among the source patients, there was a 8.0% prevalence of
      positive serology for HIV, 1.0% for HBsAg, 6.0% for anti-HBc and 3% for anti-HCV.
      Among the injured 14.0% were not immunized to hepatitis B; however, the vaccine
      and immunoglobulin prescription was lower than necessary. The results will
      subsidize the plan preventive measures and new approach towards the occurrence of
      such accidents. 

PMID- 24676079
TI  - [Microbial contamination of cuffs lab coats during health care].
AB  - The study aimed to evaluate the bacterial contamination in lab coats worn by
      nursing students, before and after being worn in health care practices. A
      quantitative and descriptive study was carried out, in which the students' coats
      were collected, washed and ironed in a standardized way and wore for four hours
      in assistance activities. Subsequently, samples from the cuffs were collected
      with sterile cotton swabs in order to be incubated in order to analyze microbial
      growth through morphological analysis by Gram's Method and antibiogram. There was
      bacterial growth of Staphylococcus aureus and Staphylococcus epidermidis in 50%
      of the collected samples and Staphylococcus aureus, found in patients with wounds
      in outpatient care, showed resistance to antibiotics such as Vancomycin,
      Chloramphenicol and Sulfonamides. The data demonstrated that the lab coats wore
      during assistance activities, even in short periods, are effectively contaminated
      by strains resistant to antibiotics and can potentially cause infection related
      to health care. 

PMID- 24676080
TI  - [Supervised curricular internship: analysis of the students' experience].
AB  - Qualitative study aimed to analyze the experience of students in the development
      of Supervised Curricular Internship activities which are part of the curricula of
      the undergraduate nursing course from a public university in the state of Sao
      Paulo, Brazil. The material for analysis was composed of the students' final
      reports taken on the end of the activities. Documental analysis was used in order
      to understand the experiences of the students. We analyzed six documents for
      which we used thematic content analysis as theoretical framework in an attempt to
      identify meanings and to obtain inferences about the documents produced. The
      reports allowed to conclude that the students' experience with the Supervised
      Curricular Internship was positive and contributed to develop a link between
      theory offered by the academy and daily routine/practice of nursing profession.
      Personal and professional growth was mentioned by the students as essential for
      them to feel empowered to act as confident and competent professionals. 

PMID- 24676081
TI  - [Des-interest in professional educating in the production of the National Seminar
      on Guidelines for Nursing Education].
AB  - Documentary, retrospective, quali-quantitative research, which aimed to examine
      the approaches of scientific productions through summaries of the 12 and 13
      national seminar on guidelines for the education in nursing, which raised the
      medium-level technical professional education in nursing. SPECIFIC OBJECTIVES:
      quantify and discuss the scientific production of events regarding the
      geographical distribution of authors, objectives and methodology of the studies.
      As a criterion for inclusion the abstracts should contain at least one of the
      following descriptors in the title and/or objectives: education in nursing,
      technical education in nursing, vocational education. Reviewed 637 abstracts, 23
      met the inclusion criteria. The production was concentrated in the Southeast
      region in Brazil and the objectives featured mainly teaching practices of the
      nurses. There was little expressiveness of vocational at the event, signaling the
      need for more studies, considering the relevance of the technical level
      professionals for the Nursing profession and the health system.

PMID- 24676082
TI  - [Dysfunctional family in the context of alcoholism: concept analysis].
AB  - Alcoholism is considered an associated factor to the family dysfunction,
      revealing the need for health professionals to overcome the purely individual
      perspective to offer a systemic focus. The aim of this study was to analyze the
      concept dysfunctional family in the context of alcoholism. The study followed the
      Concept Analysis Model and steps of integrative literature review. It was
      identifi ed the antecedents of alcoholism, the attributes and the consequent
      dysfunctional family and it was reported a model case which illustrated the
      presence of these elements. It was observed that this is a broad concept,
      subjective and complex, with emphasis on studies on the consequents related to
      children of alcoholics. 

PMID- 24676083
TI  - Hemodynamic parameters distribution of upstream, stenosis center, and downstream
      sides of plaques in carotid artery with different stenosis: a MRI and CFD study.
AB  - BACKGROUND: Histopathological studies have shown significant differences in
      plaque components and surface conditions between upstream and downstream of the
      stenosis. It can be deduced that the flow status near the plaques is different
      from the flow status at the upstream side, stenosis center, or downstream side of
      the plaque. PURPOSE: To study the hemodynamic parameter distribution in different
      locations near atherosclerotic plaques in the carotid arteries with different
      stenosis degrees. MATERIAL AND METHODS: Eleven patients were recruited in this
      study. CE-MRA was performed to obtain the carotid three-dimensional surface data
      and the stenosis degrees were calculated. The hemodynamic parameters including
      wall shear stress (WSS), pressure, and velocity near the plaques were obtained by
      computational fluid dynamic (CFD) method. Local hemodynamics parameters were
      analyzed and compared between different stenosis degree groups, and between
      upstream, stenosis center, and downstream sides of plaques. Relative ratio of
      velocity, WSS, and pressure values in different locations was calculated and
      compared. RESULTS: Fourteen carotid arteries (with 4 mild, 6 moderate, and 4
      severe stenosis) were analyzed. Significant differences were found in Pressure
      max (P = 0.025), Pressure mean (P = 0.020), and Pressure min (P = 0.026) between
      three stenosis groups. It showed significant differences in Vmin (P < 0.001) and
      WSSmin (P < 0.001) between three different locations. It showed upstream to
      downstream ratio of WSSmax (P = 0.034) and WSSmean value (P = 0.042) was
      significantly different between mild and moderate/severe groups. Significant
      differences were found in upstream to stenosis center ratio of Pressure max value
      (P = 0.018), Pressure mean value (P = 0.029), and Pressure min value (P = 0.026),
      as well as in stenosis center to downstream ratio of Pressure min value (P =
      0.042). CONCLUSION: Velocity, WSS, pressure, and relative ratio of these
      parameters have certain trends in distribution around the plaques in the carotid
      arteries.

PMID- 24676084
TI  - Endometriosis: the role of magnetic resonance imaging.
AB  - Several imaging options are available today to diagnose endometriosis. Currently,
      the two techniques most used are sonography and magnetic resonance imaging (MRI).
      Three-dimensional (3D) sonography has proved to be particularly sensitive in the
      diagnosis of endometriosis. In recent years, MRI has emerged as a high
      reproducible method to explore endometriosis; moreover, its capability to
      evaluate tissue signal is an extremely powerful system in the differential
      diagnosis with other pathologies and for the identification of malignant
      degeneration. The purpose of this paper is to present the state-of-the-art of MRI
      of endometriosis by performing a review of the literature and showing the
      epidemiology, pathogenesis, and classification of endometriosis. In this work,
      the technique that should be used, MR findings of endometriosis and the
      principles of differential diagnosis are explained. 

PMID- 24676085
TI  - DNA methyltransferase inhibitors improve the effect of chemotherapeutic agents in
      SW48 and HT-29 colorectal cancer cells.
AB  - DNA methylation is an epigenetic phenomenon known to play an important role in
      the development and progression of human cancer. Enzyme responsible for this
      process is DNA methyltransferase 1 (DNMT1) that maintains an altered methylation
      pattern by copying it from parent to daughter DNA strands after replication.
      Aberrant methylation of the promoter regions of genes critical for normal
      cellular functions is potentially reversible. Therefore, inactivation of DNMT1
      seems to be a valuable target for the development of cancer therapies. Currently,
      the most popular DNMT inhibitors (DNMTi) are cytidine analogues like 5
      azacytidine, 5-aza-2'-deoxycytidine (decitabine) and pyrimidin-2-one
      ribonucleoside (zebularine). In colorectal cancer, epigenetic modifications play
      an essential role at each step of carcinogenesis. Therefore, we have addressed
      the hypothesis that DNA methyltransferase inhibitors may potentiate inhibitory
      effects of classical chemotherapeutic agents, such as oxaliplatin and 5
      fluorouracil (5-FU), commonly used in colorectal cancer therapy. Here, our report
      shows that DNMTi can have positive interactions with standard chemotherapeutics
      in colorectal cancer treatment. Using pharmacological models for the drug-drug
      interaction analysis, we have revealed that the combination of decitabine with 5
      FU or oxaliplatin shows the most attractive interaction (synergism), whereas the
      effect of zebularine in combinations with chemotherapeutics is moderate and may
      be depended on genetic/epigenetic background of a cell line or secondary drug
      used in combination. Our results suggest that DNMTi administered in combination
      with standard chemotherapeutics might improve the treatment of patients with
      colorectal cancers. 

PMID- 24676091
TI  - Forecasting influenza epidemics from multi-stream surveillance data in a
      subtropical city of China.
AB  - BACKGROUND: Influenza has been associated with heavy burden of mortality and
      morbidity in subtropical regions. However, timely forecast of influenza epidemic
      in these regions has been hindered by unclear seasonality of influenza viruses.
      In this study, we developed a forecasting model by integrating multiple sentinel
      surveillance data to predict influenza epidemics in a subtropical city Shenzhen,
      China. METHODS: Dynamic linear models with the predictors of single or multiple
      surveillance data for influenza-like illness (ILI) were adopted to forecast
      influenza epidemics from 2006 to 2012 in Shenzhen. Temporal coherence of these
      surveillance data with laboratory-confirmed influenza cases was evaluated by
      wavelet analysis and only the coherent data streams were entered into the model.
      Timeliness, sensitivity and specificity of these models were also evaluated to
      compare their performance. RESULTS: Both influenza virology data and ILI
      consultation rates in Shenzhen demonstrated a significant annual seasonal cycle
      (p<0.05) during the entire study period, with occasional deviations observed in
      some data streams. The forecasting models that combined multi-stream ILI
      surveillance data generally outperformed the models with single-stream ILI data,
      by providing more timely, sensitive and specific alerts. CONCLUSIONS: Forecasting
      models that combine multiple sentinel surveillance data can be considered to
      generate timely alerts for influenza epidemics in subtropical regions like
      Shenzhen.

PMID- 24676092
TI  - A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential
      therapeutic for autoimmune diseases.
AB  - HsTX1 toxin, from the scorpion Heterometrus spinnifer, is a 34-residue, C
      terminally amidated peptide cross-linked by four disulfide bridges. Here we
      describe new HsTX1 analogues with an Ala, Phe, Val or Abu substitution at
      position 14. Complexes of HsTX1 with the voltage-gated potassium channels Kv1.3
      and Kv1.1 were created using docking and molecular dynamics simulations, then
      umbrella sampling simulations were performed to construct the potential of mean
      force (PMF) of the ligand and calculate the corresponding binding free energy for
      the most stable configuration. The PMF method predicted that the R14A mutation in
      HsTX1 would yield a > 2 kcal/mol gain for the Kv1.3/Kv1.1 selectivity free energy
      relative to the wild-type peptide. Functional assays confirmed the predicted
      selectivity gain for HsTX1[R14A] and HsTX1[R14Abu], with an affinity for Kv1.3 in
      the low picomolar range and a selectivity of more than 2,000-fold for Kv1.3 over
      Kv1.1. This remarkable potency and selectivity for Kv1.3, which is significantly
      up-regulated in activated effector memory cells in humans, suggest that these
      analogues represent valuable leads in the development of therapeutics for
      autoimmune diseases.

PMID- 24676096
TI  - Metal-metalloporphyrin frameworks: a resurging class of functional materials.
AB  - This review presents comprehensively recent progress in metal-metalloporphyrin
      frameworks (MMPFs) with an emphasis on versatile functionalities. Following a
      brief introduction of basic concepts and the potential virtues of MMPFs, we give
      a snapshot of the historical perspective of MMPFs since 1991. We then summarize
      four effective strategies implemented frequently to construct prototypal MMPFs.
      MMPFs represent a resurging class of promising functional materials, highlighted
      with diverse applications including guest-molecule adsorption and separation,
      catalysis, nano-thin films and light-harvesting. 

PMID- 24676093
TI  - Comparison of CAGE and RNA-seq transcriptome profiling using clonally amplified
      and single-molecule next-generation sequencing.
AB  - CAGE (cap analysis gene expression) and RNA-seq are two major technologies used
      to identify transcript abundances as well as structures. They measure expression
      by sequencing from either the 5' end of capped molecules (CAGE) or tags randomly
      distributed along the length of a transcript (RNA-seq). Library protocols for
      clonally amplified (Illumina, SOLiD, 454 Life Sciences [Roche], Ion Torrent),
      second-generation sequencing platforms typically employ PCR preamplification
      prior to clonal amplification, while third-generation, single-molecule sequencers
      can sequence unamplified libraries. Although these transcriptome profiling
      platforms have been demonstrated to be individually reproducible, no systematic
      comparison has been carried out between them. Here we compare CAGE, using both
      second- and third-generation sequencers, and RNA-seq, using a second-generation
      sequencer based on a panel of RNA mixtures from two human cell lines to examine
      power in the discrimination of biological states, detection of differentially
      expressed genes, linearity of measurements, and quantification reproducibility.
      We found that the quantified levels of gene expression are largely comparable
      across platforms and conclude that CAGE and RNA-seq are complementary
      technologies that can be used to improve incomplete gene models. We also found
      systematic bias in the second- and third-generation platforms, which is likely
      due to steps such as linker ligation, cleavage by restriction enzymes, and PCR
      amplification. This study provides a perspective on the performance of these
      platforms, which will be a baseline in the design of further experiments to
      tackle complex transcriptomes uncovered in a wide range of cell types. 

PMID- 24676095
TI  - Can I be sued for that? Liability risk and the disclosure of clinically
      significant genetic research findings.
AB  - Genomic researchers increasingly are faced with difficult decisions about
      whether, under what circumstances, and how to return research results and
      significant incidental findings to study participants. Many have argued that
      there is an ethical-maybe even a legal-obligation to disclose significant
      findings under some circumstances. At the international level, over the last
      decade there has begun to emerge a clear legal obligation to return significant
      findings discovered during the course of research. However, there is no explicit
      legal duty to disclose in the United States. This creates legal uncertainty that
      may lead to unmanaged variation in practice and poor quality care. This article
      discusses liability risks associated with the disclosure of significant research
      findings for investigators in the United States. 

PMID- 24676094
TI  - Subtelomeric CTCF and cohesin binding site organization using improved
      subtelomere assemblies and a novel annotation pipeline.
AB  - Mapping genome-wide data to human subtelomeres has been problematic due to the
      incomplete assembly and challenges of low-copy repetitive DNA elements. Here, we
      provide updated human subtelomere sequence assemblies that were extended by
      filling telomere-adjacent gaps using clone-based resources. A bioinformatic
      pipeline incorporating multiread mapping for annotation of the updated assemblies
      using short-read data sets was developed and implemented. Annotation of
      subtelomeric sequence features as well as mapping of CTCF and cohesin binding
      sites using ChIP-seq data sets from multiple human cell types confirmed that CTCF
      and cohesin bind within 3 kb of the start of terminal repeat tracts at many, but
      not all, subtelomeres. CTCF and cohesin co-occupancy were also enriched near
      internal telomere-like sequence (ITS) islands and the nonterminal boundaries of
      subtelomere repeat elements (SREs) in transformed lymphoblastoid cell lines
      (LCLs) and human embryonic stem cell (ES) lines, but were not significantly
      enriched in the primary fibroblast IMR90 cell line. Subtelomeric CTCF and cohesin
      sites predicted by ChIP-seq using our bioinformatics pipeline (but not predicted
      when only uniquely mapping reads were considered) were consistently validated by
      ChIP-qPCR. The colocalized CTCF and cohesin sites in SRE regions are candidates
      for mediating long-range chromatin interactions in the transcript-rich SRE
      region. A public browser for the integrated display of short-read sequence-based
      annotations relative to key subtelomere features such as the start of each
      terminal repeat tract, SRE identity and organization, and subtelomeric gene
      models was established. 

PMID- 24676097
TI  - Retinal hemangioblastoma regression after single session of photodynamic therapy.

PMID- 24676090
TI  - RNA-Seq reveals infection-induced gene expression changes in the snail
      intermediate host of the carcinogenic liver fluke, Opisthorchis viverrini.
AB  - BACKGROUND: Bithynia siamensis goniomphalos is the snail intermediate host of the
      liver fluke, Opisthorchis viverrini, the leading cause of cholangiocarcinoma
      (CCA) in the Greater Mekong sub-region of Thailand. Despite the severe public
      health impact of Opisthorchis-induced CCA, knowledge of the molecular
      interactions occurring between the parasite and its snail intermediate host is
      scant. The examination of differences in gene expression profiling between
      uninfected and O. viverrini-infected B. siamensis goniomphalos could provide
      clues on fundamental pathways involved in the regulation of snail-parasite
      interplay. METHODOLOGY/PRINCIPAL FINDINGS: Using high-throughput (Illumina)
      sequencing and extensive bioinformatic analyses, we characterized the
      transcriptomes of uninfected and O. viverrini-infected B. siamensis goniomphalos.
      Comparative analyses of gene expression profiling allowed the identification of
      7,655 differentially expressed genes (DEGs), associated to 43 distinct biological
      pathways, including pathways associated with immune defense mechanisms against
      parasites. Amongst the DEGs with immune functions, transcripts encoding distinct
      proteases displayed the highest down-regulation in Bithynia specimens infected by
      O. viverrini; conversely, transcription of genes encoding heat-shock proteins and
      actins was significantly up-regulated in parasite-infected snails when compared
      to the uninfected counterparts. CONCLUSIONS/SIGNIFICANCE: The present study lays
      the foundation for functional studies of genes and gene products potentially
      involved in immune-molecular mechanisms implicated in the ability of the parasite
      to successfully colonize its snail intermediate host. The annotated dataset
      provided herein represents a ready-to-use molecular resource for the discovery of
      molecular pathways underlying susceptibility and resistance mechanisms of B.
      siamensis goniomphalos to O. viverrini and for comparative analyses with
      pulmonate snail intermediate hosts of other platyhelminths including
      schistosomes.

PMID- 24676099
TI  - Bandgap engineering and manipulating electronic and optical properties of ZnO
      nanowires by uniaxial strain.
AB  - Bandgap engineering is a common practice for tuning semiconductors for desired
      physical properties. Although possible strain effects in semiconductors have been
      investigated for over a half-century, a profound understanding of their influence
      on energy bands, especially for large elastic strain remains unclear. In this
      study, a systematic investigation of the transport properties of n-type [0001]
      ZnO nanowires was performed at room temperature using the in situ scanning
      tunnelling microscope-transmission electron microscope technique which shows that
      the transport properties vary with the applied external uniaxial strain. It has
      been found that the resistance of ZnO nanowires decreases continuously with
      increasing compressive strain, but increases under increased tensile strain,
      suggesting piezo-resistive characteristics. A series of near-band-edge emissions
      were measured and the corresponding variations of bandgaps were obtained during
      the application of tensile strain of individual ZnO nanowires via
      cathodoluminescence spectroscopy. From this, a relationship between the changes
      of energy bandgap and the transport properties, both induced by uniaxial strain,
      is built. 

PMID- 24676098
TI  - Spectral parameters modulation and source localization of blink-related alpha and
      low-beta oscillations differentiate minimally conscious state from vegetative
      state/unresponsive wakefulness syndrome.
AB  - Recently, the cortical source of blink-related delta oscillations (delta BROs) in
      resting healthy subjects has been localized in the posterior cingulate
      cortex/precuneus (PCC/PCu), one of the main core-hubs of the default-mode
      network. This has been interpreted as the electrophysiological signature of the
      automatic monitoring of the surrounding environment while subjects are immersed
      in self-reflecting mental activities. Although delta BROs were directly
      correlated to the degree of consciousness impairment in patients with disorders
      of consciousness, they failed to differentiate vegetative state/unresponsive
      wakefulness syndrome (VS/UWS) from minimally conscious state (MCS). In the
      present study, we have extended the analysis of BROs to frequency bands other
      than delta in the attempt to find a biological marker that could support the
      differential diagnosis between VS/UWS and MCS. Four patients with VS/UWS, 5
      patients with MCS, and 12 healthy matched controls (CTRL) underwent standard 19
      channels EEG recordings during resting conditions. Three-second-lasting EEG
      epochs centred on each blink instance were submitted to time-frequency analyses
      in order to extract the normalized Blink-Related
      Synchronization/Desynchronization (nBRS/BRD) of three bands of interest (low
      alpha, high-alpha and low-beta) in the time-window of 50-550 ms after the blink
      peak and to estimate the corresponding cortical sources of electrical activity.
      VS/UWS nBRS/BRD levels of all three bands were lower than those related to both
      CTRL and MCS, thus enabling the differential diagnosis between MCS and VS/UWS.
      Furthermore, MCS showed an intermediate signal intensity on PCC/PCu between CTRL
      and VS/UWS and a higher signal intensity on the left temporo-parieto-occipital
      junction and inferior occipito-temporal regions when compared to VS/UWS. This
      peculiar pattern of activation leads us to hypothesize that resting MCS patients
      have a bottom-up driven activation of the task positive network and thus are
      tendentially prone to respond to environmental stimuli, even though in an almost
      unintentional way. 

PMID- 24676100
TI  - Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding
      site and miRNA-mediated regulation.
AB  - Genome-wide association studies (GWAS) have identified chromosomal loci that
      affect risk of coronary heart disease (CHD) independent of classical risk
      factors. One such association signal has been identified at 6q23.2 in both
      Caucasians and East Asians. The lead CHD-associated polymorphism in this region,
      rs12190287, resides in the 3' untranslated region (3'-UTR) of TCF21, a basic
      helix-loop-helix transcription factor, and is predicted to alter the seed binding
      sequence for miR-224. Allelic imbalance studies in circulating leukocytes and
      human coronary artery smooth muscle cells (HCASMC) showed significant imbalance
      of the TCF21 transcript that correlated with genotype at rs12190287, consistent
      with this variant contributing to allele-specific expression differences. 3' UTR
      reporter gene transfection studies in HCASMC showed that the disease-associated C
      allele has reduced expression compared to the protective G allele. Kinetic
      analyses in vitro revealed faster RNA-RNA complex formation and greater binding
      of miR-224 with the TCF21 C allelic transcript. In addition, in vitro probing
      with Pb2+ and RNase T1 revealed structural differences between the TCF21 variants
      in proximity of the rs12190287 variant, which are predicted to provide greater
      access to the C allele for miR-224 binding. miR-224 and TCF21 expression levels
      were anti-correlated in HCASMC, and miR-224 modulates the transcriptional
      response of TCF21 to transforming growth factor-beta (TGF-beta) and platelet
      derived growth factor (PDGF) signaling in an allele-specific manner. Lastly, miR
      224 and TCF21 were localized in human coronary artery lesions and anti-correlated
      during atherosclerosis. Together, these data suggest that miR-224 interaction
      with the TCF21 transcript contributes to allelic imbalance of this gene, thus
      partly explaining the genetic risk for coronary heart disease associated at
      6q23.2. These studies implicating rs12190287 in the miRNA-dependent regulation of
      TCF21, in conjunction with previous studies showing that this variant modulates
      transcriptional regulation through activator protein 1 (AP-1), suggests a unique
      bimodal level of complexity previously unreported for disease-associated
      variants. 

PMID- 24676101
TI  - Apoptosis of THP-1 derived macrophages induced by sonodynamic therapy using a new
      sonosensitizer hydroxyl acetylated curcumin.
AB  - Curcumin is extracted from the rhizomes of the traditional Chinese herb Curcuma
      longa. Our previous study indicated curcumin was able to function as a
      sonosensitizer. Hydroxyl acylated curcumin was synthesized from curcumin to
      eliminate the unstable hydroxy perssad in our group. The potential use of
      Hydroxyl acylated curcumin as a sonosensitizer for sonodynamic therapy (SDT)
      requires further exploration. This study investigated the sonodynamic effect of
      Hydroxyl acylated curcumin on THP-1 macrophage. THP-1 macrophages were cultured
      with Hydroxyl acylated curcumin at a concentration of 5.0 MUg/mL for 4 hours and
      then exposed to pulse ultrasound irradiation (0.5 W/cm2 with 1.0 MHz ) for 5 min,
      10 min and 15 min. Six hours later, cell viability decreased significantly by CCK
      8 assay. After ultrasound irradiation, the ratio of apoptosis and necrosis in SDT
      group was higher than that in control, Hydroxyl acylated curcumin alone and
      ultrasound alone. Moreover, the apoptotic rate was higher than necrotic rate with
      the flow cytometry analysis. Furthermore, Hydroxyl acylated curcumin-SDT induced
      reactive oxygen species (ROS) generation in THP-1 macrophages immediately after
      the ultrasound treatment while ROS generation was reduced significantly with the
      scavenger of singlet oxygen Sodium azide (NaN3). Hydroxyl acylated curcumin-SDT
      led to a conspicuous loss of mitochondrial membrane potential (MMP) compared with
      other groups, while MMP was increased significantly with the scavenger of singlet
      oxygen Sodium azide (NaN3), ROS inhibitor N-acetyl cysteine (NAC) and
      Mitochondrial Permeability Transition Pore (MPTP) inhibitor Cyclosporin A (CsA).
      The cytochrome C, cleaved-Caspase-9, cleaved-Caspase-3 and cleaved-PARP
      upregulated after SDT through Western blotting. These findings suggested that
      Hydroxyl acylated curcumin under low-intensity ultrasound had sonodynamic effect
      on THP-1 macrophages via generation of intracellular singlet oxygen and
      mitochondria-caspase signaling pathway, indicating that Hydroxyl acylated
      curcumin could be used as a novel sonosensitizer in SDT for atherosclerosis. 

PMID- 24676103
TI  - Not missing the train of history!

PMID- 24676104
TI  - [Factors associated with beliefs about adherence to non-pharmacological treatment
      of patients with heart failure].
AB  - This study aimed at assessing beliefs about the benefits and barriers to
      adherence to daily self-monitoring of weight/edema in patients with heart
      failure, and the influence of demographic and clinical variables on those
      beliefs. 105 patients were interviewed. The mean of the subscales Benefits and
      Barriers were 20.2 (+/- 5.7) and 30.1 (+/-7.1), respectively. Patients perceived
      that adherence to daily self-monitoring of weight/edema could keep them healthy,
      improve their quality of life and decrease the chances of readmission.
      Approximately half of patients (46.7%) reported forgetting this measure. Those
      who controlled weight once a month were more likely to have barriers to adherence
      (OR= 6.6; IC 95% 1.9-13.8; p=0.01), showing this measure to be the main factor
      related to perceived barriers. Education in health can contribute with the
      development of strategies aimed at lowering barriers and increasing benefits of
      this control. 

PMID- 24676102
TI  - Loads bias genetic and signaling switches in synthetic and natural systems.
AB  - Biological protein interactions networks such as signal transduction or gene
      transcription networks are often treated as modular, allowing motifs to be
      analyzed in isolation from the rest of the network. Modularity is also a key
      assumption in synthetic biology, where it is similarly expected that when network
      motifs are combined together, they do not lose their essential characteristics.
      However, the interactions that a network module has with downstream elements
      change the dynamical equations describing the upstream module and thus may change
      the dynamic and static properties of the upstream circuit even without explicit
      feedback. In this work we analyze the behavior of a ubiquitous motif in gene
      transcription and signal transduction circuits: the switch. We show that adding
      an additional downstream component to the simple genetic toggle switch changes
      its dynamical properties by changing the underlying potential energy landscape,
      and skewing it in favor of the unloaded side, and in some situations adding loads
      to the genetic switch can also abrogate bistable behavior. We find that an
      additional positive feedback motif found in naturally occurring toggle switches
      could tune the potential energy landscape in a desirable manner. We also analyze
      autocatalytic signal transduction switches and show that a ubiquitous positive
      feedback switch can lose its switch-like properties when connected to a
      downstream load. Our analysis underscores the necessity of incorporating the
      effects of downstream components when understanding the physics of biochemical
      network motifs, and raises the question as to how these effects are managed in
      real biological systems. This analysis is particularly important when scaling
      synthetic networks to more complex organisms. 

PMID- 24676105
TI  - [Translation and cultural adaptation of the Perceived Stigmatization
      Questionnaire for burn victims in Brazil].
AB  - This methodological study aimed to describe the process of translation and
      cultural adaptation of the Perceived stigmatization Questionnaire (PSQ) and
      analyze the internal consistency of the items in the step of pre-testing. The PSQ
      was developed to evaluate the perception of stigmatizing behaviors of burn
      victims. The adaptation process was carried out from August 2012 to February
      2013, comprising the steps outlined in the literature. As part of this process,
      the pre-test with 30 adult burn victims was held. All participants at this step
      reported to understand the instrument items and the scale of responses. There
      were no suggestions or changes in the tested version. The value of Cronbach's
      alpha at pre-test was 0.87. The contribution of this study is to describe the
      operation of each of the steps of this methodological process and show the
      internal consistency of the items in the pre-test. 

PMID- 24676106
TI  - [The existence of nursing in caring for terminally ills'life: a phenomenological
      study].
AB  - By taking care of cancer patients in their process of end of life, nursing
      experience situations of suffering before the anguish of others. This study aimed
      to understand the meaning and significance attributed by the nurses from the
      palliative care cancer hospital. This is a phenomenological research, grounded in
      Heidegger's thinking, performed with 13 nurses, who work at Oncology
      hospitalward, through semi-structured interviews, which were analyzed according
      to the steps recommended by Josgrilberg. From understanding the statementsof the
      subjects, two ontological themesemerged: Feeling satisfaction and love in the
      care offered and Feeling anger and inabilitytowards terminally ill patients.We
      inferred that working in Oncology Ward is something rewarding for these
      professionals, but it entails physical and mental suffering, from feeling
      helpless before the death-dying process. Thus, we showedthat nursing
      professionals need to be recognized as human beings and as such, also deserving
      of care. 

PMID- 24676107
TI  - [Prevalence and factors associated with incidents related to medication in
      surgical patients].
AB  - The aim of this study was to estimate the prevalence and factors associated with
      the occurrence of incidents related to medication, registered in the medical
      records of patients admitted to a Surgical Clinic, in 2010. This is a cross
      sectional study, conducted at a university hospital, with a sample of 735
      hospitalizations. Was performed the categorization of types of incidents,
      multivariate analysis of regression logistic and calculated the prevalence. The
      prevalence of drug-related incidents was estimated at 48.0% and were identified,
      as factors related to the occurrence of these incidents: length of
      hospitalization more than four days, prescribed three or more medications per day
      and realization of surgery intervention. It is expected to have contributed for
      the professionals and area managers can identify risky situations and rethink
      their actions. 

PMID- 24676108
TI  - [Content validation of the nursing diagnosis Nausea].
AB  - This study aimed to evaluate the content validity of the nursing diagnosis of
      nausea in the immediate post-operative period, considering Fehring's model.
      Descriptive study with 52 nurses experts who responded an instrument containing
      identification and validation of nausea diagnosis data. Most experts considered
      the domain 12 (Comfort), Class 1 (Physical Comfort) and the statement (Nausea)
      adequate to the diagnosis. Modifications were suggested in the current definition
      of this nursing diagnosis. Four defining characteristics were considered primary
      (reported nausea, increased salivation, aversion to food and vomiting sensation)
      and eight secondary (increased swallowing, sour taste in the mouth, pallor,
      tachycardia, diaphoresis, sensation of hot and cold, changes in blood pressure
      and pupil dilation). The total score for the diagnosis of nausea was 0.79.
      Reports of nausea, vomiting sensation, increased salivation and aversion to food
      are strong predictors of nursing diagnosis of nausea. 

PMID- 24676109
TI  - [Factors associated with vaccination against influenza A (H1N1) in the elderly].
AB  - This study aimed to investigate the sociodemographic, clinical and behavioral
      factors and receiving information about the vaccine against pandemic influenza A
      (H1N1) associated with vaccination of elderly people. Study of quantitative and
      transversal nature, in which 286 elderly residents in Fortaleza, CE, Brazil
      participated. The association between variables was analyzed by the Pearson chi
      square test, considering a 95% confidence interval and significance level
      (p<=0.05). The results revealed that, unlike the sociodemographic
      characteristics, many clinical, behavioral and informational aspects correlated
      significantly with adherence to Influenza A (H1N1) vaccination. It is believed
      that the findings can be used in strategies to control and prevent infection by
      viral subtypes within the elderly population, extensible even to other vaccine
      preventable diseases, especially in light of possible future pandemics. 

PMID- 24676110
TI  - [The relationship between depressive symptoms and family functioning in
      institutionalized elderly].
AB  - The present study aimed to investigate the relationship between family
      functioning and depressive symptoms among institutionalized elderly. This is a
      descriptive, cross-sectional study of quantitative character. A total of 107
      institutionalized elderly were assessed using a sociodemographic questionnaire,
      the Geriatric Depression Scale (to track depressive symptoms) and the Family
      APGAR (to assess family functioning). The correlation coefficient of Pearson's,
      the chi-square test and the crude and adjusted logistic regression were used in
      the data analysis with a significance level of 5 %. The institutionalized elderly
      with depressive symptoms were predominantly women and in the age group of 80
      years and older. Regarding family functioning, most elderly had high family
      dysfunctioning (57 %). Family dysfunctioning was higher among the elderly with
      depressive symptoms. There was a significant correlation between family
      functioning and depressive symptoms. The conclusion is that institutionalized
      elderly with dysfunctional families are more likely to have depressive symptoms. 

PMID- 24676111
TI  - [Organization of healthcare and assistance to the elderly indigenous population:
      synergies and particularities of the professional context].
AB  - This study aimed to describe the effects of the organization of primary
      healthcare on the assistance provided to the elderly Kaingang population,
      according to the perception of health professionals that work in this area. It is
      a qualitative and descriptive study, supported by ethnography methodological
      references, and was conducted with ten healthcare professionals that work in
      Faxinal, an indigenous territory in the state of Parana, in Brazil. Data was
      collected from November 2010 to February 2012 through participant observation and
      interviews. The results revealed that health professionals strive to meet the
      health needs of the elderly Kaingang people; however, there are negative effects
      that hinder the professional care, especially limited human resources, lack of
      training and material resources, heavy workload and high turnover rates. This
      study highlights the need to improve work conditions in order to provide better
      healthcare. 

PMID- 24676112
TI  - [Development and validation of the Family Vulnerability Index to Disability and
      Dependence (FVI-DD)].
AB  - This exploratory, descriptive, cross-sectional, and quantitative study aimed to
      develop and validate an index of family vulnerability to disability and
      dependence (FVI-DD). This study was adapted from the Family Development Index,
      with the addition of social and health indicators of disability and dependence.
      The instrument was applied to 248 families in the city of Sao Paulo, followed by
      exploratory factor analysis. Factor validation was performed using the concurrent
      and discriminant validity of the Lawton scale and Katz Index. The descriptive
      level adopted for the study was p < 0.05. The final vulnerability index comprised
      50 questions classified into seven factors contemplating social and health
      dimensions, and this index exhibited good internal consistency (Cronbach's alpha
      = 0.82). FVI-DD was validated using both the Lawton scale and Katz Index. We
      conclude that FVI-DD can accurately and reliably assess family vulnerability to
      disability and dependence. 

PMID- 24676113
TI  - [Prevalence of seropositivity for hepatitis B and C in pregnant women].
AB  - The aim of the study was to identify the prevalence of hepatitis B and C
      seropositivity in pregnant women attended in a public maternity hospital located
      in Catalao-GO from 2005 to 2009. Descriptive, exploratory study conducted through
      patients' hospital records. For data analysis, we used SPSS version 18.0. The
      confidence interval (CI) was calculated using the Person chi2 test, considering a
      significance level of 5% (p <0.05). The prevalence of HBV was 5.64% and HCV
      0.098%, predominantly in young pregnant women aged between 20 and 30 years old,
      single and in their first pregnancy. 

PMID- 24676114
TI  - Measurement of nurses' workload in an oncology outpatient clinic.
AB  - The growing demand and the degree of patient care in oncological outpatient
      services, as well as the complexity of treatment have had an impact on the
      workload of nurses. This study aimed at measuring the workload and productivity
      of nurses in an oncological outpatient service. An observational study using a
      work sampling technique was conducted and included seven nurses working in an
      oncological outpatient service in the south-eastern region of Brazil. A total of
      1,487 intervention or activity samples were obtained. Nurses used 43.2% of their
      time on indirect care, 33.2% on direct care, 11.6% on associated activities, and
      12% on personal activities. Their mean productivity was 88.0%. The findings
      showed that nurses in this service spend most of their time in indirect care
      activities. Moreover, the productivity index in this study was above that
      recommended in the literature. 

PMID- 24676115
TI  - [Direct cost of connecting, maintaining and disconnecting patient-controlled
      analgesia pump].
AB  - Quantitative research that aimed to identify the mean total cost (MTC) of
      connecting, maintaining and disconnecting patient-controlled analgesia pump (PCA)
      in the management of pain. The non-probabilistic sample corresponded to the
      observation of 81 procedures in 17 units of the Central Institute of the Clinics
      Hospital, Faculty of Medicine, University of Sao Paulo. We calculated the MTC
      multiplying by the time spent by nurses at a unit cost of direct labor, adding
      the cost of materials and medications/solutions. The MTC of connecting was R$
      107.91; maintenance R$ 110.55 and disconnecting R$ 4.94. The results found will
      subsidize discussions about the need to transfer money from the Unified Health
      System to hospitals units that perform this technique of analgesic therapy and it
      will contribute to the cost management aimed at making efficient and effective
      decision-making in the allocation of available resources. 

PMID- 24676116
TI  - [Comprehensiveness in child healthcare teaching in Undergraduate Nursing:
      perspective of teachers].
AB  - This qualitative study analyzed, from the teacher's perspective, if the principle
      of comprehensiveness is included in child healthcare teaching in nursing
      education. The participants were 16 teachers involved in teaching child
      healthcare in eight undergraduate nursing programs. Data collection was performed
      through interviews that were submitted to thematic content analysis. The theory
      in teaching incorporates comprehensive care, as it is based on children's
      epidemiological profile, child healthcare policies and programs, and included
      interventions for the promotion/prevention/rehabilitation in primary health care,
      hospitals, daycare centers and preschools. The comprehensive conception of health
      disease process allows for understanding the child within his/her family and
      community. However, a contradiction exists between what is proposed and what is
      practiced, because the teaching is fragmented, without any integration among
      disciplines, with theory dissociated from practice, and isolated practical
      teaching that compromises the incorporation of the principle of comprehensiveness
      in child healthcare teaching. 

PMID- 24676117
TI  - [Teaching-service integration: implications and roles in experiences of
      undergraduate courses in nursing].
AB  - The study aimed at understanding the implications of the teaching-service
      integration to nursing education from the perspective of teachers, students and
      professionals in Primary Healthcare as well as identifying the roles of teachers
      and professionals who follow practical experiences in education. This is a case
      study of qualitative approach carried out in five undergraduate courses in
      Nursing in the state of Santa Catarina. A total of 22 teachers and 14
      professionals were interviewed and five focus groups were conducted with
      students. Results are presented in two categories: Implications of the teaching
      service integration to education in Nursing: contributing factors and intervening
      factors and Relationships established in the experiences: a unison speech and a
      dissonant practice. The contributions of the teaching-service integration are
      undeniable. Despite this belief, there are intervening factors that need to be on
      the agenda for discussion. The role of facilitator in education emerged strongly
      despite conflicting perceptions remain. 

PMID- 24676118
TI  - [Warning systems in a computerized nursing process for Intensive Care Units].
AB  - A hybrid study combining technological production and methodological research
      aiming to establish associations between the data and information that are part
      of a Computerized Nursing Process according to the ICNP(r) Version 1.0,
      indicators of patient safety and quality of care. Based on the guidelines of the
      Agency for Healthcare Research and Quality and the American Association of
      Critical Care Nurses for the expansion of warning systems, five warning systems
      were developed: potential for iatrogenic pneumothorax, potential for care-related
      infections, potential for suture dehiscence in patients after abdominal or pelvic
      surgery, potential for loss of vascular access, and potential for endotracheal
      extubation. The warning systems are a continuous computerized resource of
      essential situations that promote patient safety and enable the construction of a
      way to stimulate clinical reasoning and support clinical decision making of
      nurses in intensive care. 

PMID- 24676119
TI  - [Social use of alcohol among adolescent offenders: a fundamental approach toward
      human needs].
AB  - This study examined some basic health care approaches toward human needs, with a
      particular focus on nursing. We aimed to incorporate these approaches into the
      discussion of the mental health of adolescent offenders who consume alcohol. We
      discuss specific needs of the delinquent group, critique policies that prioritize
      coercion of adolescent offenders, and the role that nurses could play in the
      sphere of juvenile delinquency. 

PMID- 24676120
TI  - [Nursing concepts and theories].
AB  - The theory framework of nursing science is built in a dynamic process that arises
      from practice and is reproduced through research, mainly by analysis and
      development of concepts and theories. This study presents a theory reflection on
      nursing knowledge construction and points out subsidies for future studies in the
      area. The interrelation among theory, research, and clinical practice is required
      for continuous development of nursing as a profession and science. Ideally, the
      practice must be based on theory that is validated by research. Therefore,
      theory, research, and practice affect each other reciprocally and continuously. 

PMID- 24676121
TI  - [Analysis of variables that are not directly observable: influence on decision
      making during the research process].
AB  - The sample dimension, types of variables, format used for measurement, and
      construction of instruments to collect valid and reliable data must be considered
      during the research process. In the social and health sciences, and more
      specifically in nursing, data-collection instruments are usually composed of
      latent variables or variables that cannot be directly observed. Such facts
      emphasize the importance of deciding how to measure study variables (using an
      ordinal scale or a Likert or Likert-type scale). Psychometric scales are examples
      of instruments that are affected by the type of variables that comprise them,
      which could cause problems with measurement and statistical analysis (parametric
      tests versus non-parametric tests). Hence, investigators using these variables
      must rely on suppositions based on simulation studies or recommendations based on
      scientific evidence in order to make the best decisions. 

PMID- 24676122
TI  - [Nursing: promoting the health of overweight children and adolescents in the
      school context].
AB  - The study aimed to analyze the nursing interventions related to the competencies
      of health promotion of overweight children and adolescents in the school context,
      in light of the Galway Consensus through an integrative review. Articles
      published between 1988 and June, 2013 were found in the databases CINAHL, SCOPUS,
      MEDLINE/PubMed, Cochrane, LILACS and SciELO. A total of 139 publications were
      obtained from indexed descriptors. Ten articles were selected after reading. The
      most evident competencies for health promotion were: catalyzing change, needs
      assessment and impact assessment. The highlights were activities of health
      education and partnerships with other health professionals and the families of
      students. It was found that the skills of health promotion developed by nurses
      can contribute to the adoption of healthy habits by overweight children and
      adolescents. 

PMID- 24676123
TI  - [Scientific production on the applicability of phenytoin in wound healing].
AB  - Phenytoin is an anticonvulsant that has been used in wound healing. The
      objectives of this study were to describe how the scientific production presents
      the use ofphenytoinas a healing agent and to discuss its applicability in wounds.
      A literature review and hierarchy analysis of evidence-based practices was
      performed. Eighteen articles were analyzed that tested the intervention in wounds
      such as leprosy ulcers, leg ulcers, diabetic foot ulcers, pressure ulcers,
      trophic ulcers, war wounds, burns, preparation of recipient graft area,
      radiodermatitis and post-extraction of melanocytic nevi. Systemic use
      ofphenytoinin the treatment of fistulas and the hypothesis of topical use in the
      treatment of vitiligo were found. In conclusion, topical use ofphenytoinis
      scientifically evidenced. However robust research is needed that supports a
      protocol for the use ofphenytoinas another option of a healing agent in clinical
      practice. 

PMID- 24676124
TI  - [Duration of smoking cessation for the prevention of surgical wound healing
      complications].
AB  - The study aimed to find scientific evidence about the duration of preoperative
      smoking cessation required to reduce surgical wound healing complications. An
      integrative review was performed in the databases, Latin American and Caribbean
      Literature on Health Sciences (LILACS) and Medical Literature Analysis and
      Retrieval System Online (MEDLINE), from 08/17/2012 to 09/17/2012, using the
      keywords: tobacco use cessation and wound healing; tobacco use cessation and
      preoperative period; tobacco use cessation and perioperative period (LILACS) and
      tobacco use cessation and perioperative period; tobacco use cessation and wound
      healing (MEDLINE). Out of the 81 eligible studies, 12 were included. The duration
      of smoking cessation needed to reduce healing complications was at least four
      weeks (four studies with level of evidence I, three studies with level of
      evidence II, two studies with level of evidence IV, and one study with level of
      evidence VII). 

PMID- 24676125
TI  - [Instrumental and ethical aspects of experimental research with animal models].
AB  - Experimental animal models offer possibilities of physiology knowledge,
      pathogenesis of disease and action of drugs that are directly related to quality
      nursing care. This integrative review describes the current state of the
      instrumental and ethical aspects of experimental research with animal models,
      including the main recommendations of ethics committees that focus on animal
      welfare and raises questions about the impact of their findings in nursing care.
      Data show that, in Brazil, the progress in ethics for the use of animals for
      scientific purposes was consolidated with Law No. 11.794/2008 establishing
      ethical procedures, attending health, genetic and experimental parameters. The
      application of ethics in handling of animals for scientific and educational
      purposes and obtaining consistent and quality data brings unquestionable
      contributions to the nurse, as they offer subsidies to relate pathophysiological
      mechanisms and the clinical aspect on the patient. 

PMID- 24676127
TI  - Recent advances in porous polyoxometalate-based metal-organic framework
      materials.
AB  - Polyoxometalate (POM)-based metal-organic framework (MOF) materials contain POM
      units and generally generate MOF materials with open networks. POM-based MOF
      materials, which utilize the advantages of both POMs and MOFs, have received
      increasing attention, and much effort has been devoted to their preparation and
      relevant applications over the past few decades. They have good prospects in
      catalysis owing to the electronic and physical properties of POMs that are
      tunable by varying constituent elements. In this review, we present recent
      developments in porous POM-based MOF materials, including their classification,
      synthesis strategies, and applications, especially in the field of catalysis. 

PMID- 24676126
TI  - Superiority of pulmonary administration of mepenzolate bromide over other routes
      as treatment for chronic obstructive pulmonary disease.
AB  - We recently proposed that mepenzolate bromide (mepenzolate) would be
      therapeutically effective against chronic obstructive pulmonary disease (COPD)
      due to its both anti-inflammatory and bronchodilatory activities. In this study,
      we examined the benefits and adverse effects associated with different routes of
      mepenzolate administration in mice. Oral administration of mepenzolate caused not
      only bronchodilation but also decreased the severity of elastase-induced
      pulmonary emphysema; however, compared with the intratracheal route of
      administration, about 5000 times higher dose was required to achieve this effect.
      Intravenously or intrarectally administered mepenzolate also showed these
      pharmacological effects. The intratracheal route of mepenzolate administration,
      but not other routes, resulted in protective effects against elastase-induced
      pulmonary damage and bronchodilation at a much lower dose than that which
      affected defecation and heart rate. These results suggest that the pulmonary
      route of mepenzolate administration may be superior to other routes (oral,
      intravenous or intrarectal) to treat COPD patients. 

PMID- 24676129
TI  - Risk factors for invasive pneumococcal disease in HIV-infected adults in France
      in the highly active antiretroviral therapy era.
AB  - Invasive pneumococcal diseases remain frequent and severe in HIV-infected
      subjects. To identify opportunities for prevention, we assessed risk factors of
      invasive pneumococcal diseases (IPD) in HIV-infected patients over a 10-year
      period in France. We performed a retrospective case-control study in a reference
      centre of HIV management in Paris. All HIV-infected patients having suffered from
      IPD between 2000 and 2011 were included. Control subjects were HIV-infected with
      no history of IPD or pneumonia, matched by date of diagnosis of HIV with
      controls. Two controls were randomly selected for each subject. In all, 42 HIV
      infected patients presented 44 IPD episodes during the study period and were
      compared to 84 controls. In the multivariate analysis, patients with IPD were
      more likely than controls to have a Charlson Comorbidity Index >=2 (adjusted OR =
      7.07, 95% CI 1.99-25.1, p = 0.003), CD4-cell count <200/cells/uL (aOR = 6.93, 95%
      CI 1.80-26.7, p = 0.005), HIV-RNA viral load >400 copies/mL (aOR = 5.56, 95% CI
      1.58-19.5, p = 0.007) and a non-European origin (aOR = 4.26, 95% CI 1.02-17.9, p
      = 0.047). HIV-infected patients with a higher burden of comorbidities,
      uncontrolled HIV replication, low CD4-cell counts and/or of non-European origin
      are at higher risk of developing IPD. Better screening for and management of HIV
      infection is necessary to reduce the risk of IPD.

PMID- 24676130
TI  - Sexual history taking in general practice: managing sexually transmitted
      infections for female sex workers by doctors and assistant doctors in Vietnam.
AB  - Sexually transmitted infections (STIs) in Vietnam have been increasing. Control
      of STIs among female sex workers (FSWs) is important in controlling the epidemic.
      Effective STI control requires that physicians are skilful in taking sexual
      history for FSW patients. Three hundred and seventy-one physicians responded to a
      survey conducted in three provinces in Vietnam. The respondents were asked
      whether they asked FSW patients about their sexual history and information asked
      during sexual history taking. The respondents were also asked about their
      barriers for taking sexual history. Over one-fourth (27%) respondents always,
      over half (54%) respondents sometimes and 19% respondents never obtained a sexual
      history from FSW patients. Multivariable analysis revealed that factors
      associated with always taking a sexual history were being doctor, training in
      STIs and working at provincial level facilities. Physician's discomfort was found
      to be inversely associated with training on communication with patients, seeing
      15 or fewer patients a week, working at provincial level facilities. Issues in
      sexual history taking among FSW patients in general practice in Vietnam were
      identified. These issues can help STI control for FSW patients and need due
      attention in order to improve STI management in Vietnam. 

PMID- 24676131
TI  - Behcet's disease - part of the differential diagnosis of ulcerative lesions.
AB  - This case describes a young white British man with a one-year history of
      recurrent genital ulceration managed by the GP. Initially this was thought to be
      a drug reaction; however, presentation at our genitourinary medicine clinic and
      onward review with dermatology allowed the diagnosis of Behcet's disease to be
      made. The clinical diagnosis was made based on painful oral and genital ulcers,
      eye irritation, erythema nodosum and positive pathergy test. Treatment with oral
      prednisolone was initiated by dermatology, which resulted in rapid improvement in
      the genital ulceration. This case highlights that clinicians should consider
      Behcet's disease in patients with recurrent genital ulceration to ensure prompt
      diagnosis and prevention of systemic involvement. 

PMID- 24676132
TI  - Awareness and utilization of HIV services of an AIDS community-based organization
      in Kuala Lumpur, Malaysia.
AB  - In Malaysia, homosexuality is illegal; little is known about access to HIV
      prevention services among Malaysian men who have sex with men (MSM). We analysed
      PT Foundation outreach data to describe the profiles among MSM who accessed PT
      Foundation services and to examine factors associated with being aware of PT
      Foundation and having visited the organization. A survey was administered during
      weekly outreach throughout Kuala Lumpur from March-December 2012. Pearson's Chi
      square tests were used to compare demographic and behavioural characteristics of
      participants who were and were not aware of the PT Foundation. Binary logistic
      regression was used to identify correlates of MSM visiting the PT Foundation
      among those who had heard of the organization. Of 614 MSM, this study found
      significantly higher awareness of the PT Foundation among MSM who perceived they
      had "good" HIV knowledge (p = .026) and participants who reported always using
      condoms (p = .009). MSM who reported being paid for sex were 2.81 times as likely
      to visit the PT Foundation compared to men who did not. A subgroup of MSM known
      to be at high risk for HIV infection is accessing prevention services. Future
      studies should uncover motivations and barriers of accessing these services among
      MSM in Malaysia.

PMID- 24676133
TI  - Single nucleotide polymorphisms of microRNA processing machinery genes and
      outcome of hepatocellular carcinoma.
AB  - MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) can affect
      cancer development, treatment efficacy and patients prognosis. We examined 6 miR
      SNPs in miRNA processing machinery genes including exportin 5 (XPO5) (rs11077),
      Ran-GTPase (RAN) (rs14035), Dicer (rs3742330), Trinucleotide Repeat Containing 6B
      (TNRC6B) (rs9623117), GEMIN3 (rs197412), GEMIN4 (rs2740348) in 108 surgically
      resected HCC patients and evaluated the impact of these miR-SNPs on HCC outcome.
      Among the 6 SNPs, only the A/A genotype of rs11077 located in XPO5 3'UTR was
      identified to associated independently with worse survival in HCC patients by
      multivariate analysis with relative risk, 0.395; 95% CI, 0.167-0.933; p = 0.034.
      This is the first study reporting that polymorphisms related to miRSNPs have
      prognostic value in hepatocellular carcinoma and identify the A/A genotype of
      rs11077 SNP site located in XPO5 3'UTR can help to predict worse prognosis in
      patients.

PMID- 24676134
TI  - Microarray profiling and co-expression network analysis of circulating lncRNAs
      and mRNAs associated with major depressive disorder.
AB  - LncRNAs, which represent one of the most highly expressed classes of ncRNAs in
      the brain, are becoming increasingly interesting with regard to brain functions
      and disorders. However, changes in the expression of regulatory lncRNAs in Major
      Depressive Disorder (MDD) have not yet been reported. Using microarrays, we
      profiled the expression of 34834 lncRNAs and 39224 mRNAs in peripheral blood
      sampled from MDD patients as well as demographically-matched controls. Among
      these, we found that 2007 lncRNAs and 1667 mRNAs were differentially expressed,
      17 of which were documented as depression-related gene in previous studies. Gene
      Ontology (GO) and pathway analyses indicated that the biological functions of
      differentially expressed mRNAs were related to fundamental metabolic processes
      and neurodevelopment diseases. To investigate the potential regulatory roles of
      the differentially expressed lncRNAs on the mRNAs, we also constructed co
      expression networks composed of the lncRNAs and mRNAs, which shows significant
      correlated patterns of expression. In the MDD-derived network, there were a
      greater number of nodes and connections than that in the control-derived network.
      The lncRNAs located at chr10:874695-874794, chr10:75873456-75873642, and
      chr3:47048304-47048512 may be important factors regulating the expression of
      mRNAs as they have previously been reported associations with MDD. This study is
      the first to explore genome-wide lncRNA expression and co-expression with mRNA
      patterns in MDD using microarray technology. We identified circulating lncRNAs
      that are aberrantly expressed in MDD and the results suggest that lncRNAs may
      contribute to the molecular pathogenesis of MDD. 

PMID- 24676135
TI  - Salmonella adhesion, invasion and cellular immune responses are differentially
      affected by iron concentrations in a combined in vitro gut fermentation-cell
      model.
AB  - In regions with a high infectious disease burden, concerns have been raised about
      the safety of iron supplementation because higher iron concentrations in the gut
      lumen may increase risk of enteropathogen infection. The aim of this study was to
      investigate interactions of the enteropathogen Salmonella enterica ssp. enterica
      Typhimurium with intestinal cells under different iron concentrations encountered
      in the gut lumen during iron deficiency and supplementation using an in vitro
      colonic fermentation system inoculated with immobilized child gut microbiota
      combined with Caco-2/HT29-MTX co-culture monolayers. Colonic fermentation
      effluents obtained during normal, low (chelation by 2,2'-dipyridyl) and high iron
      (26.5 mg iron/L) fermentation conditions containing Salmonella or pure Salmonella
      cultures with similar iron conditions were applied to cellular monolayers.
      Salmonella adhesion and invasion capacity, cellular integrity and immune response
      were assessed. Under high iron conditions in pure culture, Salmonella adhesion
      was 8-fold increased compared to normal iron conditions while invasion was not
      affected leading to decreased invasion efficiency (-86%). Moreover, cellular
      cytokines IL-1beta, IL-6, IL-8 and TNF-alpha secretion as well as NF-kappaB
      activation in THP-1 cells were attenuated under high iron conditions. Low iron
      conditions in pure culture increased Salmonella invasion correlating with an
      increase in IL-8 release. In fermentation effluents, Salmonella adhesion was 12
      fold and invasion was 428-fold reduced compared to pure culture. Salmonella in
      high iron fermentation effluents had decreased invasion efficiency (-77.1%) and
      cellular TNF-alpha release compared to normal iron effluent. The presence of
      commensal microbiota and bacterial metabolites in fermentation effluents reduced
      adhesion and invasion of Salmonella compared to pure culture highlighting the
      importance of the gut microbiota as a barrier during pathogen invasion. High iron
      concentrations as encountered in the gut lumen during iron supplementation
      attenuated Salmonella invasion efficiency and cellular immune response suggesting
      that high iron concentrations alone may not lead to an increased Salmonella
      invasion. 

PMID- 24676136
TI  - Molecular mechanisms of pulmonary arterial remodeling.
AB  - Pulmonary arterial hypertension (PAH) is characterized by a persistent elevation
      of pulmonary arterial pressure and pulmonary arterial remodeling with unknown
      etiology. Current therapeutics available for PAH are primarily directed at
      reducing the pulmonary blood pressure through their effects on the endothelium.
      It is well accepted that pulmonary arterial remodeling is primarily due to
      excessive pulmonary arterial smooth muscle cell (PASMC) proliferation that leads
      to narrowing or occlusion of the pulmonary vessels. Future effective therapeutics
      will be successful in reversing the vascular remodeling in the pulmonary arteries
      and arterioles. The purpose of this review is to provide updated information on
      molecular mechanisms involved in pulmonary arterial remodeling with a focus on
      growth factors, transcription factors, and epigenetic pathways in PASMC
      proliferation. In addition, this review will highlight novel therapeutic
      strategies for potentially reversing PASMC proliferation. 

PMID- 24676138
TI  - Progress in the synthesis and exploitation of catenanes since the Millennium.
AB  - Catenanes - molecules consisting of interlocked macrocyclic rings - have been
      prepared by templation strategies for some thirty years. The utilization of Cu(I)
      cation, aromatic donor-acceptor interactions and hydrogen bonding assisted self
      assembly strategies has led to the construction of numerous examples of these
      aesthetically pleasing species. This review seeks to discuss key developments in
      the synthesis and functional application of catenanes that have occurred since
      the Millennium. The much expanded range of metal cation templates; the genesis
      and growth of anion templation, as well as the use of alternative supramolecular
      interactions (halogen bonding and radical templation) and thermodynamically
      controlled reactions to synthesize catenanes are detailed. The class of catenanes
      that may be described as "molecular machines" are then highlighted and to
      conclude, attempts to fabricate catenanes onto surfaces and into metal organic
      frameworks (MOFs) are discussed. 

PMID- 24676137
TI  - RNA sequence reveals mouse retinal transcriptome changes early after axonal
      injury.
AB  - Glaucoma is an ocular disease characterized by progressive retinal ganglion cell
      (RGC) death caused by axonal injury. However, the underlying mechanisms involved
      in RGC death remain unclear. In this study, we investigated changes in the
      transcriptome profile following axonal injury in mice (C57BL/6) with RNA
      sequencing (RNA-seq) technology. The experiment group underwent an optic nerve
      crush (ONC) procedure to induce axonal injury in the right eye, and the control
      group underwent a sham procedure. Two days later, we extracted the retinas and
      performed RNA-seq and a pathway analysis. We identified 177 differentially
      expressed genes with RNA-seq, notably the endoplasmic reticulum (ER) stress
      related genes Atf3, Atf4, Atf5, Chac1, Chop, Egr1 and Trb3, which were
      significantly upregulated. The pathway analysis revealed that ATF4 was the most
      significant upstream regulator. The antioxidative response-related genes Hmox1
      and Srxn1, as well as the immune response-related genes C1qa, C1qb and C1qc, were
      also significantly upregulated. To our knowledge, this is the first reported RNA
      seq investigation of the retinal transcriptome and molecular pathways in the
      early stages after axonal injury. Our results indicated that ER stress plays a
      key role under these conditions. Furthermore, the antioxidative defense and
      immune responses occurred concurrently in the early stages after axonal injury.
      We believe that our study will lead to a better understanding of and insight into
      the molecular mechanisms underlying RGC death after axonal injury. 

PMID- 24676139
TI  - Antiretroviral therapy as a factor protective against anal dysplasia in HIV
      infected males who have sex with males.
AB  - OBJECTIVES: Chronic infection with oncogenic HPV genotype is associated with the
      development of anal dysplasia. Antiretroviral therapy (ART) has been shown to
      decrease the incidence of cervical carcinoma in women with HIV. We sought to: 1)
      describe the prevalence and grade of anal dysplasia and HPV infection in our
      study subjects; 2) analyze the grade of correlation between anal cytology, PCR of
      high-risk HPV, and histology; 3) identify the factors associated with the
      appearance of >= AIN2 lesions. DESIGN: Cross-sectional, prospective study.
      METHODS: A cohort of HIV-positive males (n = 140, mean age  = 37 years) who have
      sex with males (MSM) had epidemiological, clinical and analytical data collected.
      Anal mucosa samples were taken for cytology, HPV PCR genotyping, and anoscopy for
      histological analysis. RESULTS: Within the cohort, 77.1% were being treated with
      ART, 8.5% anoscopy findings were AIN2, and 11.4% carcinoma in situ; 74.2% had
      high-risk (HR), 59.7% low-risk (LR) HPV genotypes and 46.8% had both. The
      combination of cytology with PCR identifying HR-HPV better predicts the histology
      findings than either of these factors alone. Logistic regression highlighted ART
      as a protective factor against >= AIN2 lesions (OR: 0.214; 95%CI: 0.054-0.84).
      Anal/genital condylomas (OR: 4.26; 95%CI: 1.27-14.3), and HPV68 genotype (OR:
      10.6; 95%CI: 1.23-91.47) were identified as risk factors. CONCLUSIONS: In our
      cohort, ART has a protective effect against dysplastic anal lesions. Anal/genital
      warts and HPV68 genotype are predictors of >= AIN2 lesions. Introducing PCR HPV
      genotype evaluation improves screening success over that of cytology alone.

PMID- 24676140
TI  - Survivin transcript variant 2 drives angiogenesis and malignant progression in
      proneural gliomas.
AB  - BACKGROUND: The influence of survivin isoforms on outcome in glioblastoma is
      poorly understood. We analyzed the dominant anti-apoptotic transcript variants of
      survivin using expression data and modeled them in vivo to determine their impact
      on glioma formation and progression. METHODS: Using data from low- and high-grade
      glioma knowledge bases, we expressed the anti-apoptotic isoforms of survivin
      (transcript variants 1 and 2) in vivo using the RCAS/Ntv-a model of murine
      glioma. RESULTS: In low-grade gliomas, survivin RNA expression was increased in
      22 of 167 (13.2%) of cases and was associated with shortened survival (P = .005).
      Survivin RNA was preferentially expressed in proneural (PN) relative to
      mesenchymal high-grade gliomas (P < .0001). In proneural gliomas, survivin was
      expressed in 94 of 141 (67%) of cases and was associated with shorter disease
      free survival (P = .04). In a platelet-derived growth factor subunit B-dependent
      murine model of PN glioma, ectopic expression of variant 1 yielded tumors in 28
      of 30 (93%) of mice, of which 25% were high-grade tumors, whereas ectopic
      expression of variant 2 yielded tumors in 27 of 28 (96%), of which 81% were high
      grade tumors (P < .0001). Microvascular proliferation was significantly more
      prominent (P < .0001), and tumor-free survival was shorter in mice with variant 2
      than variant 1-derived tumors (P = .01). CONCLUSIONS: Survivin expression in low
      grade gliomas is associated with poor survival and is preferentially expressed in
      PN gliomas. Compared with variant 1, variant 2 was associated with poorer
      survival and promoted malignant progression, angiogenesis, and shorter tumor-free
      survival in the PN murine model. Inhibiting survivin transcript variant 2, rather
      than variant 1 (the common isoform), may be an effective treatment strategy for
      glioma.

PMID- 24676142
TI  - Ndae1 expression and regulation in Drosophila embryos.
AB  - The construction and prediction of cell fate maps at the whole embryo level
      require the establishment of an accurate atlas of gene expression patterns
      throughout development and the identification of the corresponding cis-regulatory
      sequences. However, while the expression and regulation of genes encoding
      upstream developmental regulators such as transcription factors or signaling
      pathway components have been analyzed in detail, up to date the number of cis
      regulatory sequences identified for downstream effector genes, like ion channels,
      pumps and exchangers, is very low. The control and regulation of ion homeostasis
      in each cell, including at blastoderm stages, are essential for normal embryonic
      development. In this study, we analyzed in detail the embryonic expression
      pattern and cis-regulatory modules of the Drosophila Na+-driven anion exchanger 1
      (Ndae1) gene, involved in the regulation of pH homeostasis. We show that Ndae1 is
      expressed in a tight and complex spatial-temporal pattern. In particular, we
      report that this downstream effector gene is under the control of the canonical
      dorsal-ventral patterning cascade through dorsal, Toll, twist and snail at early
      embryogenesis. Moreover, we identify several cis-regulatory modules, some of
      which control discrete and non-overlapping aspects of endogenous gene expression
      throughout development. 

PMID- 24676141
TI  - Trypsin- and Chymotrypsin-like serine proteases in schistosoma mansoni-- 'the
      undiscovered country'.
AB  - BACKGROUND: Blood flukes (Schistosoma spp.) are parasites that can survive for
      years or decades in the vasculature of permissive mammalian hosts, including
      humans. Proteolytic enzymes (proteases) are crucial for successful parasitism,
      including aspects of invasion, maturation and reproduction. Most attention has
      focused on the 'cercarial elastase' serine proteases that facilitate skin
      invasion by infective schistosome larvae, and the cysteine and aspartic proteases
      that worms use to digest the blood meal. Apart from the cercarial elastases,
      information regarding other S. mansoni serine proteases (SmSPs) is limited. To
      address this, we investigated SmSPs using genomic, transcriptomic, phylogenetic
      and functional proteomic approaches. METHODOLOGY/PRINCIPAL FINDINGS: Genes
      encoding five distinct SmSPs, termed SmSP1 - SmSP5, some of which comprise
      disparate protein domains, were retrieved from the S. mansoni genome database and
      annotated. Reverse transcription quantitative PCR (RT- qPCR) in various
      schistosome developmental stages indicated complex expression patterns for SmSPs,
      including their constituent protein domains. SmSP2 stood apart as being massively
      expressed in schistosomula and adult stages. Phylogenetic analysis segregated
      SmSPs into diverse clusters of family S1 proteases. SmSP1 to SmSP4 are trypsin
      like proteases, whereas SmSP5 is chymotrypsin-like. In agreement, trypsin-like
      activities were shown to predominate in eggs, schistosomula and adults using
      peptidyl fluorogenic substrates. SmSP5 is particularly novel in the phylogenetics
      of family S1 schistosome proteases, as it is part of a cluster of sequences that
      fill a gap between the highly divergent cercarial elastases and other family S1
      proteases. CONCLUSIONS/SIGNIFICANCE: Our series of post-genomics analyses
      clarifies the complexity of schistosome family S1 serine proteases and highlights
      their interrelationships, including the cercarial elastases and, not least, the
      identification of a 'missing-link' protease cluster, represented by SmSP5. A
      framework is now in place to guide the characterization of individual proteases,
      their stage-specific expression and their contributions to parasitism, in
      particular, their possible modulation of host physiology.

PMID- 24676143
TI  - The effect of massive weight loss status, amount of weight loss, and method of
      weight loss on body contouring outcomes.
AB  - BACKGROUND: The impact of massive weight loss (MWL) on body contouring procedures
      and outcomes has not been firmly established in the literature. OBJECTIVE: The
      authors investigate the correlations between MWL status, the method of achieving
      MWL, and the amount of weight lost with wound-healing complications after body
      contouring procedures. METHODS: The charts of 450 patients (124 of whom had
      undergone MWL) who underwent body contouring procedures including abdominoplasty,
      brachioplasty, thighplasty, breast mastopexy/reduction, lower bodylift, bodylift,
      buttock lift, and liposuction were reviewed. MWL patients were classified as
      having achieved weight loss through diet and exercise, gastric banding or
      sleeving, or gastric bypass. Postoperative complication data were collected,
      including cases of infection, delayed wound healing, seroma, hematoma,
      dehiscence, and overall wound problems. Odds ratios (OR) were estimated using 4
      multivariate logistic regression models. RESULTS: MWL status was a significant
      predictor of wound problems (OR, 2.69; P < .001). Patients with 50 to 100 lbs of
      weight loss did not have a significantly increased risk of wound problems (OR,
      1.93; P = .085), while patients with over 100 lbs of weight loss did (OR, 3.98; P
      < .001). Gastric bypass (OR, 3.01; P = <.001) had a higher risk correlation than
      did diet and exercise (OR, 2.72, P = .023) or restrictive bariatric surgery (OR,
      2.31; P = .038) as a weight loss method. Patients who lost over 100 lbs
      demonstrated increased risk of complications if they had gastric bypass or
      restrictive procedures. CONCLUSIONS: MWL was a significant risk factor for wound
      complications in the body contouring population. Method and amount of weight loss
      were also significant factors in predicting complications.

PMID- 24676144
TI  - Liposuction and lipofilling for treatment of symptomatic silicone toxicosis of
      the gluteal region.
AB  - BACKGROUND: Silicone injection can cause numerous posttreatment complications
      including debilitating pain, cellulitis, abscesses, overlying skin compromise,
      and siliconomas distorting overlying tissues-that can be difficult to manage.
      OBJECTIVES: The authors evaluate liposuction as a treatment for patients
      experiencing complications from silicone injections to the gluteal region, to
      both preserve aesthetic appearance and minimize further risk of complication from
      these procedures. METHODS: Eight patients (7 women and 1 man) who presented
      consecutively to us between 2010 and 2013 with complications from silicone
      injections to their gluteal region were enrolled in this study. Each patient was
      evaluated by computed tomography scan and a 0 to 6 visual analog scale for pain.
      Emergency room (ER) visits, previous hospital admissions, and cellulitis
      requiring antibiotics in the 12 months prior to treatment were recorded. Patients
      were treated with ultrasonic and standard liposuction followed by lipotransfer
      into the gluteal musculature. A Student t test was used for statistical
      comparison of pre- and postoperative values. RESULTS: Average patient age was 36
      years (range, 25-43 years). All patients initially presented with intense pain as
      assessed by a visual analog scale; by the 12th week postoperatively, the entire
      cohort experienced remission in pain. At 1 year postoperatively, no patients had
      infections (vs 75% preoperatively; P = .028), visited the ER (vs 50%
      preoperatively; P = .058), or were hospitalized (vs an average of 1.5
      hospitalizations per patient preoperatively; P = .066). CONCLUSIONS: Liposuction
      with immediate intramuscular fat transfer for buttock augmentation appears to be
      a safe surgical option that preserves aesthetic appearance for patients with
      gluteal silicone toxicosis.

PMID- 24676145
TI  - Surgical outcomes following rectus muscle plication: a potentially reversible,
      vessel-sparing alternative to resection.
AB  - IMPORTANCE: Extraocular muscle strengthening is a common treatment for
      strabismus. Plication is an alternative procedure for strengthening muscles with
      less tissue trauma than resection. OBJECTIVE: To compare the surgical dose effect
      of plication with that of resection. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective comparison of surgical outcomes in an academic pediatric
      ophthalmology and strabismus practice from July 25, 2005, through March 28, 2013,
      with a mean follow-up of 137 days for plication and 1243 days for resection. A
      single surgeon performed all procedures. Twenty-two consecutive patients
      underwent bilateral horizontal rectus plication or plication combined with
      antagonist recession (13 with esotropia and 9 with exotropia; mean [SD] age, 38
      [21] years). Thirty-one consecutive patients underwent bilateral resection or
      resection combined with antagonist recession (12 with esotropia and 19 with
      exotropia; mean [SD] age, 28 [24] years). Six patients underwent vertical rectus
      plication. EXPOSURES: Rectus resection or plication performed by folding the
      anterior tendon posteriorly under the muscle margins oversewn to the poles of the
      scleral insertion, avoiding the anterior ciliary arteries. MAIN OUTCOMES AND
      MEASURES: Postoperative binocular alignment at the first postoperative and last
      available examinations. RESULTS: Lateral rectus plication (mean [SD], 6.5 [2.2]
      mm) and resection (6.6 [1.6] mm) were performed for similar magnitudes of
      esotropia (27.9 [13.4] prism diopters [PD] for plication, 29.0 [15.2] PD for
      resection; P = .44). Mean (SD) initial correction by lateral rectus plication was
      5.17 (0.29) PD/mm, slightly less than the 95% CI (5.51-7.75 PD/mm) for resection
      (6.63 [0.50] PD/mm). Medial rectus plication (mean [SD], 4.9 [0.9] mm) vs
      resection (5.1 [1.1] mm) was performed for similar magnitudes of exotropia (32.8
      [14.2] PD for plication, 31.2 [15.6] PD for resection; P = .33). Mean (SD)
      initial correction by medial rectus plication (7.10 [1.65] PD/mm) was within the
      95% CI (4.65-9.87 PD/mm) for resection (7.26 [1.23] PD/mm). Initial and late
      effects were similar. Ciliary circulation observed at surgery remained patent
      after plication. Plication was cosmetically acceptable and did not produce
      conspicuous tissue elevations. CONCLUSIONS AND RELEVANCE: Horizontal rectus
      muscle plication is a rapidly performed, technically simple surgical procedure to
      strengthen the rectus muscles, with an equivalent (per millimeter) in surgical
      effect to that of medial rectus resection for treatment of esotropia and
      exotropia. Plication diminishes surgical trauma and does not intentionally
      sacrifice ciliary circulation, with the potential for reversal by suture release
      in the first postoperative days.

PMID- 24676146
TI  - Statistical physics approach to quantifying differences in myelinated nerve
      fibers.
AB  - We present a new method to quantify differences in myelinated nerve fibers. These
      differences range from morphologic characteristics of individual fibers to
      differences in macroscopic properties of collections of fibers. Our method uses
      statistical physics tools to improve on traditional measures, such as fiber size
      and packing density. As a case study, we analyze cross-sectional electron
      micrographs from the fornix of young and old rhesus monkeys using a semi
      automatic detection algorithm to identify and characterize myelinated axons. We
      then apply a feature selection approach to identify the features that best
      distinguish between the young and old age groups, achieving a maximum accuracy of
      94% when assigning samples to their age groups. This analysis shows that the best
      discrimination is obtained using the combination of two features: the fraction of
      occupied axon area and the effective local density. The latter is a modified
      calculation of axon density, which reflects how closely axons are packed. Our
      feature analysis approach can be applied to characterize differences that result
      from biological processes such as aging, damage from trauma or disease or
      developmental differences, as well as differences between anatomical regions such
      as the fornix and the cingulum bundle or corpus callosum. 

PMID- 24676147
TI  - Parent-of-origin effects implicate epigenetic regulation of experimental
      autoimmune encephalomyelitis and identify imprinted Dlk1 as a novel risk gene.
AB  - Parent-of-origin effects comprise a range of genetic and epigenetic mechanisms of
      inheritance. Recently, detection of such effects implicated epigenetic mechanisms
      in the etiology of multiple sclerosis (MS), a chronic inflammatory disease of the
      central nervous system. We here sought to dissect the magnitude and the type of
      parent-of-origin effects in the pathogenesis of experimental neuroinflammation
      under controlled environmental conditions. We investigated inheritance of an MS
      like disease in rat, experimental autoimmune encephalomyelitis (EAE), using a
      backcross strategy designed to identify the parental origin of disease
      predisposing alleles. A striking 37-54% of all detected disease-predisposing loci
      depended on parental transmission. Additionally, the Y chromosome from the
      susceptible strain contributed to disease susceptibility. Accounting for parent
      of-origin enabled more powerful and precise identification of novel risk factors
      and increased the disease variance explained by the identified factors by 2-4
      fold. The majority of loci displayed an imprinting-like pattern whereby a gene
      expressed only from the maternal or paternal copy exerts an effect. In
      particular, a locus on chromosome 6 comprises a well-known cluster of imprinted
      genes including the paternally expressed Dlk1, an atypical Notch ligand. Disease
      predisposing alleles at the locus conferred lower Dlk1 expression in rats and,
      together with data from transgenic overexpressing Dlk1 mice, demonstrate that
      reduced Dlk1 drives more severe disease and modulates adaptive immune reactions
      in EAE. Our findings suggest a significant epigenetic contribution to the
      etiology of EAE. Incorporating these effects enables more powerful and precise
      identification of novel risk factors with diagnostic and prognostic implications
      for complex disease. 

PMID- 24676148
TI  - Hepatic beta-oxidation and regulation of carnitine palmitoyltransferase (CPT) I
      in blunt snout bream Megalobrama amblycephala fed a high fat diet.
AB  - High-fat diets may promote growth, partly through their protein-sparing effects.
      However, high-fat diets often lead to excessive fat deposition, which may have a
      negative impact on fish such as poor growth and suppressive immune. Therefore,
      this study investigated the effects of a fat-rich diet on the mechanisms of fat
      deposition in the liver. Three-hundred blunt snout bream (Megalobrama
      amblycephala) juveniles (initial mass 18.00 +/- 0.05 g) were fed with one of two
      diets (5% or 15% fat) for 8 weeks. beta-Oxidation capacity and regulation of rate
      limiting enzymes were assessed. Large fat droplets were present in hepatocytes of
      fish fed the high-fat diet. This observation is thought to be largely owing to
      the reduced capacity for mitochondrial and peroxisomal beta-oxidation in the
      livers of fish fed the high-fat diet, as well as the decreased activities of
      carnitine palmitoyltransferase (CPT) I and acyl-CoA oxidase (ACO), which are
      enzymes involved in fatty-acid metabolism. Study of CPT I kinetics showed that
      CPT I had a low affinity for its substrates and a low catalytic efficiency in
      fish fed the high-fat diet. Expression of both CPT I and ACO was significantly
      down-regulated in fish fed the high-fat diet. Moreover, the fatty-acid
      composition of the mitochondrial membrane varied between the two groups. In
      conclusion, the attenuated beta-oxidation capacity observed in fish fed a high
      fat diet is proposed to be owing to decreased activity and/or catalytic
      efficiency of the rate-limiting enzymes CPT I and ACO, via both genetic and non
      genetic mechanisms.

PMID- 24676149
TI  - Correction of distortion in flattened representations of the cortical surface
      allows prediction of V1-V3 functional organization from anatomy.
AB  - Several domains of neuroscience offer map-like models that link location on the
      cortical surface to properties of sensory representation. Within cortical visual
      areas V1, V2, and V3, algebraic transformations can relate position in the visual
      field to the retinotopic representation on the flattened cortical sheet. A limit
      to the practical application of this structure-function model is that the cortex,
      while topologically a two-dimensional surface, is curved. Flattening of the
      curved surface to a plane unavoidably introduces local geometric distortions that
      are not accounted for in idealized models. Here, we show that this limitation is
      overcome by correcting the geometric distortion induced by cortical flattening.
      We use a mass-spring-damper simulation to create a registration between
      functional MRI retinotopic mapping data of visual areas V1, V2, and V3 and an
      algebraic model of retinotopy. This registration is then applied to the flattened
      cortical surface anatomy to create an anatomical template that is linked to the
      algebraic retinotopic model. This registered cortical template can be used to
      accurately predict the location and retinotopic organization of these early
      visual areas from cortical anatomy alone. Moreover, we show that prediction
      accuracy remains when extrapolating beyond the range of data used to inform the
      model, indicating that the registration reflects the retinotopic organization of
      visual cortex. We provide code for the mass-spring-damper technique, which has
      general utility for the registration of cortical structure and function beyond
      the visual cortex. 

PMID- 24676150
TI  - A reference pan-genome approach to comparative bacterial genomics: identification
      of novel epidemiological markers in pathogenic Campylobacter.
AB  - The increasing availability of hundreds of whole bacterial genomes provides
      opportunities for enhanced understanding of the genes and alleles responsible for
      clinically important phenotypes and how they evolved. However, it is a
      significant challenge to develop easy-to-use and scalable methods for
      characterizing these large and complex data and relating it to disease
      epidemiology. Existing approaches typically focus on either homologous sequence
      variation in genes that are shared by all isolates, or non-homologous sequence
      variation--focusing on genes that are differentially present in the population.
      Here we present a comparative genomics approach that simultaneously approximates
      core and accessory genome variation in pathogen populations and apply it to
      pathogenic species in the genus Campylobacter. A total of 7 published
      Campylobacter jejuni and Campylobacter coli genomes were selected to represent
      diversity across these species, and a list of all loci that were present at least
      once was compiled. After filtering duplicates a 7-isolate reference pan-genome,
      of 3,933 loci, was defined. A core genome of 1,035 genes was ubiquitous in the
      sample accounting for 59% of the genes in each isolate (average genome size of
      1.68 Mb). The accessory genome contained 2,792 genes. A Campylobacter population
      sample of 192 genomes was screened for the presence of reference pan-genome loci
      with gene presence defined as a BLAST match of >= 70% identity over >= 50% of the
      locus length--aligned using MUSCLE on a gene-by-gene basis. A total of 21 genes
      were present only in C. coli and 27 only in C. jejuni, providing information
      about functional differences associated with species and novel epidemiological
      markers for population genomic analyses. Homologs of these genes were found in
      several of the genomes used to define the pan-genome and, therefore, would not
      have been identified using a single reference strain approach.

PMID- 24676151
TI  - Mesoporous nano/micro noble metal particles: synthesis and applications.
AB  - The morphology, size and composition often govern the physical and chemical
      properties of noble metal units with a size in the nano or micro scale. Thus, the
      controlled growth of noble metal crystals would help to tailor their unique
      properties and this would be followed by their practical application. Mesoporous
      nano/micro noble metal units are types of nanostructured material that have
      fascinating properties that can generate great potential for various
      applications. This review presents a general view on the growth mechanisms of
      porous noble metal units and is focused on recent progresses in their synthetic
      approaches. Then, their potential applications in the field of drug delivery,
      cell imaging and SERS substrates, as well as fuel cell catalysts are overviewed. 

PMID- 24676153
TI  - New parasite in a coprolite of 240 million years, biogeography of fossil
      coelacanths, and the influence of air pollutants in a coastal area of
      northeastern Brazil.

PMID- 24676152
TI  - PET/SPECT imaging agents for neurodegenerative diseases.
AB  - Single photon emission computed tomography (SPECT) or positron emission computed
      tomography (PET) imaging agents for neurodegenerative diseases have a significant
      impact on clinical diagnosis and patient care. The examples of Parkinson's
      Disease (PD) and Alzheimer's Disease (AD) imaging agents described in this paper
      provide a general view on how imaging agents, i.e. radioactive drugs, are
      selected, chemically prepared and applied in humans. Imaging the living human
      brain can provide unique information on the pathology and progression of
      neurodegenerative diseases, such as AD and PD. The imaging method will also
      facilitate preclinical and clinical trials of new drugs offering specific
      information related to drug binding sites in the brain. In the future, chemists
      will continue to play important roles in identifying specific targets,
      synthesizing target-specific probes for screening and ultimately testing them by
      in vitro and in vivo assays. 

PMID- 24676159
TI  - Note on the paleobiogeography of Compsognathidae (Dinosauria: Theropoda) and its
      paleoecological implications.
AB  - The paleobiogeography of the theropod clade Compsognathidae is here reaccessed in
      order to test the hypothesis of this taxon being adapted specifically to inhabit
      semi-arid environments. Data about localities where these fossils were collected
      and their paleoenvironments were gathered from the literature. Compsognathids
      seem to be found especially in sedimentary deposits known as Fossil Lagerstatten,
      which were formed under a set of specific conditions that allowed the
      preservation of the fragile bone remains of these animals. This bias limits an
      accurate analysis of the historical and/or ecological paleobiogeography of this
      taxon. Actually, it is possible that compsognathids had an almost worldwide
      distribution during the Mesozoic Era. Their occurrence in Lower Cretaceous rocks
      of China suggests that they also inhabited environments with moist conditions
      instead of being restricted to semi-arid to arid environments. 

PMID- 24676160
TI  - A new Xenacanthiformes shark (Chondrichthyes, Elasmobranchii) from the Late
      Paleozoic Rio do Rasto Formation (Parana Basin), Southern Brazil.
AB  - The Brazilian records on Xenacanthiformes include teeth and cephalic spines from
      the Parnaiba, Amazonas and Parana basins. This work describes a new species of
      Xenacanthidae, collected in an outcrop of Serrinha Member of Rio do Rasto
      Formation (Wordian to Wuchiapingian), Parana Basin, municipality of Jacarezinho,
      State of Parana. The teeth of the new species are two or three-cuspidated and the
      aboral surface show a smooth concavity and one rounded basal tubercle. The
      coronal surface presents one semi-spherical and subcircular coronal button, and
      also two lateral main cusps and one central (when present) with less than one
      fifth of the size of the lateral cusps in the labial portion. The lateral cusps
      are asymmetric or symmetric, rounded in transversal section, lanceolate in
      longitudinal section, devoid of lateral carinae and lateral serrations, and with
      few smooth cristae of enameloid. In optical microscope the teeth show a
      trabecular dentine (osteodentine) base, while the cusps are composed by
      orthodentine, and the pulp cavities are non-obliterated by trabecular dentine.
      The fossil assemblage in the same stratigraphical level and in the whole Rio do
      Rasto Formation indicates another freshwater record for xenacanthid sharks. 

PMID- 24676163
TI  - Different slopes of a mountain can determine the structure of ferns and
      lycophytes communities in a tropical forest of Brazil.
AB  - A community of Ferns and Lycophytes was investigated by comparing the occurrence
      of species on different slopes of a paleoisland in Southeastern Brazil. Our goal
      was to evaluate the hypothesis that slopes with different geographic orientations
      determine a differentiation of Atlantic Forest ferns and lycophytes community. We
      recorded these plants at slopes turned towards the continent and at slopes turned
      towards the open sea. Analysis consisted of a preliminary assessment on fern beta
      diversity, a Non Metric Multidimensional Scaling (NMDS) and a Student t-test to
      confirm if sites sampling units ordination was different at each axis. We further
      used the Pearson coefficient to relate fern species to the differentiation
      pattern and again Student's t-test to determine if richness, plant cover and
      abundance varied between the two sites. There was a relatively low number of
      shared species between the two sites and ferns and lycophytes community variation
      was confirmed. Some species were detected as indicators of the community
      variation but we were unable to detect richness, plant cover or abundance
      differences. Despite the evidence of this variation between the slopes, further
      works are needed to evaluate which processes are contributing to determine this
      pattern. 

PMID- 24676164
TI  - Juvenile development of Callinectes danae Smith, 1869 (Crustacea, Decapoda,
      Brachyura, Portunidae) under laboratory conditions.
AB  - The juvenile development of Callinectes danae was investigated from megalopae
      obtained in neuston samples at Ubatuba, Sao Paulo, Brazil. The individuals were
      raised in the laboratory under constant temperature (25 +/- 1 degrees C),
      filtered sea water from the collection location (350/00), and natural
      photoperiod. Newly hatched Artemia sp. nauplii were offered as food on a daily
      basis and ornamental-fish food was also provided for the juveniles from the 4th
      stage on. Twelve stages of the juvenile phase were obtained. The main
      morphological features that allowed recognition of the first juvenile stage were
      drawn and described. All the subsequent stages obtained were examined and
      measured, and the main changes in relation to the first stage were recorded.
      Sexual dimorphism becomes apparent from the fourth juvenile stage onwards. Some
      appendages and morphological features proved to be of great importance in the
      identification of species, including the number of segments of the antennal
      flagellum and the number of setae on the maxilla and on the 1st, 2nd and 3rd
      maxillipeds. These can probably be used for future comparisons and species
      identifications. 

PMID- 24676165
TI  - Feeding habits of the leaf litter frog Haddadus binotatus (Anura, Craugastoridae)
      from two Atlantic Forest areas in southeastern Brazil.
AB  - Haddadus binotatus is an endemic anuran of the Brazilian Atlantic Forest and
      currently, there is no information about the diet of this species. We analyzed
      the diet of two populations of this anuran in two states in southeast Brazil.
      Samplings were carried out in 2004 in the state of Rio de Janeiro and in 2009 and
      2010 in the state of Espirito Santo. Haddadus binotatus presented a rich diet
      composition, preying 19 prey types. Orthoptera, Coleoptera, and Blattodea were
      the most important preys in the Rio de Janeiro population, and Orthoptera,
      Araneae and Hemiptera were the most important in the Espirito Santo population.
      The diet composition differed numerically between the two localities, but not in
      terms of volume, which can reflect local differences in the prey availability in
      the two habitats. The jaw width limited the size of prey, which is expected for
      predators who swallow the preys without chewing. The proportion of individuals
      with empty stomachs was higher in the Rio de Janeiro population (39.2%) than in
      the Espirito Santo population (17.9%), suggesting that the former could be in a
      lower energy balance. The females of the species were larger than the males,
      which may result from the production of larger eggs. 

PMID- 24676166
TI  - Antioxidant potential and cytotoxic activity of two red seaweed species, Amansia
      multifida and Meristiella echinocarpa, from the coast of Northeastern Brazil.
AB  - Natural antioxidants found in marine macroalgae are bioactive compounds known to
      play an important role in the prevention of diseases associated with aging cells
      protecting them against the oxidative damage. The purpose of this study was to
      evaluate the antioxidant and cytotoxic activity of ethanolic extracts of two
      species of red seaweeds, Amansia multifida and Meristiella echinocarpa. In vitro
      antioxidant activity was determined by DPPH radical scavenging assay, ferric
      reducing antioxidant power (FRAP) assay, ferrous ion chelating (FIC) assay, beta
      carotene bleaching (BCB) assay and total phenolic content (TPC) quantification.
      Cytotoxicity was evaluated with the brine shrimp Artemia sp. lethality test. The
      TPC values observed in the present study indicated that both species A. multifida
      and M. echinocarpa are rich in phenolic compounds, reaching values of 45.40 and
      28.46 mg gallic acid equivalent (GAE) g-1 of ethanolic extract, respectively.
      DPPH radical scavenging and ferrous ion chelating showed values of 60% and 17%,
      respectively. Both seaweed extracts inhibited beta-carotene oxidation by
      approximately 40%. None of the algal extracts were potentially cytotoxic. The
      results have showed that extracts of both species of marine red algae exhibit
      antioxidant potential and low toxicity. They are sources of natural antioxidant
      compounds. 

PMID- 24676167
TI  - Histological features, starch accumulation and sprouting in the early root
      development of Jacaranda ulei (Bignoniaceae).
AB  - The plant species occurring in the savanna region of the Cerrado biome in Brazil
      present typical morphological and physiological adaptations to a dry climate with
      seasonal occurrence of wildfires. In this study, the histological features of the
      root system, the main sites of synthesis and storage of starch and the initial
      phases of the bud development were characterized in Jacaranda ulei. The
      anatomical features observed in the root system of J. ulei are related to the
      needs of the species to survive in the Cerrado. The histochemical analyses
      demonstrated high synthesis of glucose and glycoprotein after the third day of in
      vitro culture, in the proximal cells of the cortical parenchyma of the exoderm.
      Meristematic primordia were observed in the ninth day and the beginning of the
      meristem formation was observed after 21 days of in vitro culture. Jacaranda ulei
      displays morphological, anatomical and storage features typical from resprouter
      species. However, it may be vulnerable to unsustainable exploitation. Considering
      the importance of this species for local people, more studies regarding its
      therapeutic properties should be performed, including the planning of appropriate
      programs for the species management and the production of selected clones through
      in vitro micropropagation. 

PMID- 24676168
TI  - Evaluation of micro-energy dispersive X-ray fluorescence and histochemical tests
      for aluminium detection in plants from High Altitude Rocky Complexes, Southeast
      Brazil.
AB  - The soils developed under High Altitude Rocky Complexes in Brazil are generally
      of very low chemical fertility, with low base saturation and high exchangeable
      aluminium concentration. This stressful condition imposes evolutionary pressures
      that lead to ecological success of plant species that are able to tolerate or
      accumulate high amounts of aluminium. Several analytical methods are currently
      available for elemental mapping of biological structures, such as micro-X-ray
      fluorescence (MU-EDX) and histochemical tests. The aim of this study was to
      combine MU-EDX analysis and histochemical tests to quantify aluminium in plants
      from High Altitude Rocky Complexes, identifying the main sites for Al
      accumulation. Among the studied species, five showed total Al concentration
      higher than 1000 mg kg-1. The main Al-hyperaccumulator plants, Lavoisiera
      pectinata, Lycopodium clavatum and Trembleya parviflora presented positive
      reactions in the histochemical tests using Chrome Azurol and Aluminon. Strong
      positive correlations were observed between the total Al concentrations and data
      obtained by MU-EDX analysis. The MU-EDX analysis is a potential tool to map and
      quantify Al in hyperaccumulator species, and a valuable technique due to its non
      destructive capacity. Histochemical tests can be helpful to indicate the
      accumulation pattern of samples before they are submitted for further MU-EDX
      scrutiny. 

PMID- 24676169
TI  - Cyanobacteria, microcystins and cylindrospermopsin in public drinking supply
      reservoirs of Brazil.
AB  - Brazil has a history of blooms and contamination of freshwater systems by
      cyanobacterial toxins. The monitoring relevance of toxins from cyanobacteria in
      reservoirs for public supply is notorious given its high toxicity to mammals,
      included humans beings. The most recurrent toxins in Brazilian water bodies are
      microcystins (MC). However, the recent record of cylindrospermopsin (CYN) in
      northeastern Brazil, Pernambuco state, alerts us to the possibility that this
      could be escalating. This study reports occurrence of MC and CYN, quantified with
      ELISA, in 10 reservoirs, devoted to public drinking supply in northeastern
      Brazil. The composition and quantification of the cyanobacteria community
      associated with these water bodies is also presented. From 23 samples
      investigated for the presence of MC, and CYN, 22 and 8 out were positive,
      respectively. Considering the similarity of the cyanobacteria communities found
      in reservoirs from Pernambuco, including toxin-producing species associated to MC
      and CYN, we suggest that geographic spreading can be favored by these factors.
      These issues emphasize the need for increased monitoring of MC and CYN in
      drinking supply reservoirs in Brazil. 

PMID- 24676170
TI  - Splendid oddness: revisiting the curious trophic relationships of South American
      Pleistocene mammals and their abundance.
AB  - The South American Pleistocene mammal fauna includes great-sized animals that
      have intrigued scientists for over two centuries. Here we intend to update the
      knowledge on its palaeoecology and provide new evidence regarding two approaches:
      energetics and population density and relative abundance of fossils per taxa. To
      determine whether an imbalance exists, population density models were applied to
      several South American fossil faunas and the results compared to those that best
      describe the palaeoecology of African faunas. The results on the abundance study
      for Uruguay and the province of Buenos Aires during the Lujanian stage/age reveal
      that bulk-feeding ground sloths (Lestodon and Glossotherium) were more
      represented in the first territory, while the more selective Scelidotherium and
      Megatherium were more abundant in the second. Although the obtained values were
      corrected to avoid size-related taphonomic biases, linear regressions of
      abundance vs. body mass plots did not fit the expected either for first or second
      consumers. South American Pleistocene faunas behave differently from what models
      suggest they should. Changes in sea level and available area could account for
      these differences; the possibility of a floodplain in the area then emerged could
      explain seasonal changes, which would modify the calculations of energetics and
      abundance. 

PMID- 24676171
TI  - Use of intertidal areas by shrimps (Decapoda) in a Brazilian Amazon estuary.
AB  - The present work investigated the occupation and the correlation of the shrimp
      abundance in relation to environmental variables in different habitats
      (mangroves, salt marshes and rocky outcrops) in an Amazon estuary. The
      collections were made in August and November 2009, at low syzygy tide on Areua
      Beach, situated in the Extractive Reserve of Mae Grande de Curuca, Para, Brazil
      totaling 20 pools. In each environment, we recorded the physical-chemical factors
      (pH, salinity, and temperature) and measured the area (m2) and volume (m3) of
      every pool through bathymetry. The average pH, salinity, temperature, area and
      volume of tide pools were 8.75 (+/- 0.8 standard deviation), 35.45 (+/- 3), 29.49
      degrees C (+/- 2.32), 27.41 m2 (+/- 41.18), and 5.19 m3 (+/- 8.01),
      respectively. We caught a total of 4,871 shrimps, distributed in three families
      and four species: Farfantepenaeus subtilis (98.36%) (marine) followed by Alpheus
      pontederiae (0.76%) (estuarine), Macrobrachium surinamicum (0.45%) and
      Macrobrachium amazonicum (0.43%) predominantly freshwater. The species F.
      subtilis and A. pontederiae occurred in the three habitats, whereas M.
      surinamicum occurred in salt marsh and rocky outcrop and M. amazonicum only in
      marisma. Temperature and pH were the most important environmental descriptors
      that significantly affected the density and biomass of shrimps. 

PMID- 24676172
TI  - Oil collecting bees and Byrsonima cydoniifolia A. Juss. (Malpighiaceae)
      interactions: the prevalence of long-distance cross pollination driving
      reproductive success.
AB  - Oil-collecting bees are the natural pollinators of oil-flower plants, but little
      is known about the pollination process and the effectiveness of their pollination
      service to the reproductive success of their host plants. In species of Byrsonima
      the reproductive system have been described as auto-compatible or self
      incompatible. We studied the reproductive system of Byrsonima cydoniifolia, the
      fructification by means of short, medium and long-distance cross pollinations,
      the morphology and floral biology and the pollination interactions with species
      of oil-collecting bees. By means of controlled pollinations we found self
      incompatibility caused by abortion of most self-pollinated flowers and
      demonstrated that the prevailing cross pollination ensuring the reproductive
      success of B. cydoniifolia is the long-distance cross pollination and Centridini
      bees; Epicharis nigrita, particularly, are the pollinators promoting the gene
      flow between genetically distinct populations. 

PMID- 24676173
TI  - Habitat structural effect on squamata fauna of the restinga ecosystem in
      northeastern Brazil.
AB  - In this work, we surveyed data on richness and composition of squamatan reptiles
      and habitat structural effect in nine areas of restinga ecosystem in the State of
      Bahia, northeastern Brazil. The "restinga" ecosystems are coastal sand dune
      habitats on the coast of Brazil. Our main hypothesis is that the Squamata fauna
      composition along these restinga areas would be modulated by habitat structural.
      After 90 days of field sampling we recorded approximately 5% of reptile species
      known in Brazil. The composition of Squamata assemblages varied mainly based on
      the presence or absence of lizards of the genera Ameivula and Tropidurus. Our
      data showed that habitat structure consistently affected the composition of local
      Squamata fauna, especially lizards. 

PMID- 24676174
TI  - Effects of Jatropha curcas oil in Lactuca sativa root tip bioassays.
AB  - Jatropha curcas L. (Euphorbiaceae) is important for biofuel production and as a
      feed ingredient for animal. However, the presence of phorbol esters in the oil
      and cake renders the seeds toxic. The toxicity of J. curcas oil is currently
      assessed by testing in animals, leading to their death. The identification of
      toxic and nontoxic improved varieties is important for the safe use of J. curcas
      seeds and byproducts to avoid their environmental toxicity. Hence, the aim of
      this study was to propose a short-term bioassay using a plant as a model to
      screen the toxicity of J. curcas oil without the need to sacrifice any animals.
      The toxicity of J. curcas oil was evident in germination, root elongation and
      chromosomal aberration tests in Lactuca sativa. It was demonstrated that J.
      curcas seeds contain natural compounds that exert phyto-, cyto- and genotoxic
      effects on lettuce, and that phorbol esters act as aneugenic agents, leading to
      the formation of sticky chromosomes and c-metaphase cells. In conclusion, the
      tests applied have shown reproducibility, which is important to verify the extent
      of detoxification and to determine toxic doses, thus reducing the numbers of
      animals that would be used for toxicity tests. 

PMID- 24676175
TI  - Diet and niche breadth and overlap in fish communities within the area affected
      by an Amazonian reservoir (Amapa, Brazil).
AB  - We investigated the niche breadth and overlap of the fish species occurring in
      four environments affected by the Coaracy Nunes reservoir, in the Amapa Brazilian
      State. Seasonal samples of fishes were taken using a standard configuration of
      gillnets, as well as dragnets, lines, and cast-nets. Five hundred and forty
      stomach contents, representing 47 fish species were analyzed and quantified.
      Niche breadth and overlap were estimated using indexes of Levins and Pianka,
      respectively, while interspecific competition was evaluated using a null model
      (RA3). ANOVA and the Kruskal-Wallis test were used, respectively, to evaluate
      differences in niche breadth and overlap between areas. The data indicate that
      the majority of the fish species belong to the piscivore, omnivore, and
      detritivore guilds. These species have likely colonized the environments due to
      the availability of suitable feeding resources, and the favorable physical
      conditions created by the river damming. Overall, few species have ample niches,
      but most of them are highly specialized. Resources seasonal variation had little
      effect on the feeding behavior of most species in the study areas. The null
      models indicated that competition was not a factor determining on community
      structure. 

PMID- 24676176
TI  - Pollen types and levels of total phenolic compounds in propolis produced by Apis
      mellifera L. (Apidae) in an area of the Semiarid Region of Bahia, Brazil.
AB  - Twenty-two propolis samples produced by Apis mellifera L. in an area of the
      Semiarid region the the State of Bahia (Agreste of Alagoinhas), Brazil, were
      palynologically analyzed and quantified regarding their levels of total phenolic
      compounds. These samples were processed using the acetolysis technique with the
      changes suggested for use with propolis. We found 59 pollen types belonging to 19
      families and 36 genera. The family Fabaceae was the most representative in this
      study with nine pollen types, followed by the family Asteraceae with seven types.
      The types Mikania and Mimosa pudica occurred in all samples analyzed. The types
      Mimosa pudica and Eucalyptus had frequency of occurrence above 50% in at least
      one sample. The highest similarity index (c. 72%) occurred between the samples
      ER1 and ER2, belonging to the municipality of Entre Rios. Samples from the
      municipality of Inhambupe displayed the highest (36.78+/-1.52 mg/g EqAG) and
      lowest (7.68 +/- 2.58 mg/g EqAG) levels of total phenolic compounds. Through the
      Spearman Correlation Coefficient we noticed that there was a negative linear
      correlation between the types Mimosa pudica (rs = -0.0419) and Eucalyptus (rs = 
      0.7090) with the profile of the levels of total phenolic compounds of the
      samples. 

PMID- 24676177
TI  - Effect of indigo dye effluent on the growth, biomass production and phenotypic
      plasticity of Scenedesmus quadricauda (Chlorococcales).
AB  - The effect of indigo dye effluent on the freshwater microalga Scenedesmus
      quadricauda ABU12 was investigated under controlled laboratory conditions. The
      microalga was exposed to different concentrations of the effluent obtained by
      diluting the dye effluent from 100 to 175 times in bold basal medium (BBM). The
      growth rate of the microalga decreased as indigo dye effluent concentration
      increased (p <0.05). The EC50 was found to be 166 dilution factor of the
      effluent. Chlorophyll a, cell density and dry weight production as biomarkers
      were negatively affected by high indigo dye effluent concentration, their levels
      were higher at low effluent concentrations (p <0.05). Changes in coenobia size
      significantly correlated with the dye effluent concentration. A shift from large
      to small coenobia with increasing indigo dye effluent concentration was obtained.
      We conclude that even at low concentrations; effluents from textile industrial
      processes that use indigo dye are capable of significantly reducing the growth
      and biomass production, in addition to altering the morphological characteristics
      of the freshwater microalga S. quadricauda. The systematic reduction in the
      number of cells per coenobium observed in this study further confirms that
      environmental stress affects coenobium structure in the genus Scenedesmus, which
      means it can be considered an important biomarker for toxicity testing. 

PMID- 24676178
TI  - Half-ironman induces changes in the kidney function of triathletes.
AB  - Long duration exercise may lead to the occurrence of urine abnormalities. Aiming
      to investigate the effects of triathlon training and competition on the renal
      function, twelve male triathletes (32.60 +/- 5.10 years, 175.04 +/- 6.67m, 71.83
      +/- 7.42Kg) were studied during the 12-week training protocol and after a Half
      Ironman. Urine was collected in M-1 - beginning of the training season, M-2 -
      before the competition and M-3 - after the half ironman. Urine pH was measured
      using reagent strips, density with a refractometer, proteinuria by Bradford
      assay, creatinine with a colorimetric assay and blood cells by microscopy. Data
      were analyzed using Shapiro-Wilk test, One-Way ANOVA and Tukey-Kramer test (p <
      0,05). Changes were found after the competition in the protein (M-1= 7.41 +/-
      2.48; M-2= 7.57 +/- 3.74; M-3= 86.10 +/- 76.21 mg/mL), creatinine (M-1= 157.66 +/
      41.59; M-2= 177.68 +/- 44.46; M-3= 316.46 +/- 132.86 mg/mL), erythrocytes (M-1=
      1060.00 +/- 0.30; M-2= 1142.86 +/- 377.96; M-3= 52555.56 +/- 58.65 units/mL) and
      leucocytes (M-1= 2375.00 +/- 744.02; M-2= 2090.00 +/- 0.50; M-3= 5000.00 +/-
      2738.60 units/mL) excretion when compared to the other collection times. These
      effects are probably due to the exercise-induced modifications in the glomerular
      membrane and endocrine variables such as anti diuretic hormone, catecholamines
      and aldosterone. 

PMID- 24676179
TI  - Patterns of antimicrobial therapy in acute tonsillitis: A cross-sectional
      hospital-based study from UAE.
AB  - BACKGROUND: Diseases of the ear, nose and throat (ENT) are associated with
      significant impairment of the daily life and a major cause for absenteeism from
      work. AIM: The study determined antimicrobial prescription pattern in patients
      with acute tonsillitis. MATERIALS AND METHODS: A cross-sectional study was
      carried out among all the patients attending the ENT department with acute
      tonsillitis. Data were retrieved from the medical records using a proforma.
      Statistical analysis was carried out using SPSS.19. RESULTS: Total of 238
      patients included (Males 138; females 100). About 96% of total drugs were
      prescribed by generic name. Median number of drugs prescribed was four (range 1
      7). Eighty eight percent of prescriptions contained antimicrobials, (78.5%)
      analgesics and (57.9%) antipyretics. Amoxicillin / Clavulanic acid (24.8%) and
      Ceftriaxone (12.2%) were the most commonly prescribed antimicrobials. Parenteral
      route was preferred in 41.6%. About 23.7% of the patients on Amoxicillin /
      Clavulanic acid had received the drug as intravenous injection. Culture and
      sensitivity tests were carried out in 106 (44.5%) of the cases. Antimicrobials
      were changed / added after the culture and sensitivity test in 25 patients.
      CONCLUSION: Study findings highlighted rational practices in drug prescribing.
      Therapeutic guidelines based on current sensitivity pattern optimize the use of
      antimicrobial agents.

PMID- 24676180
TI  - Fruit quality preservation of 'Laetitia' plums under controlled atmosphere
      storage.
AB  - The objective of this study was to evaluate the effect of controlled atmosphere
      (CA) on quality preservation of 'Laetitia' plums, mainly on internal breakdown,
      in order to determine the best CA storage conditions. Two experiments were
      carried out one in 2010, and another in 2011. In 2010, besides cold storage (CS;
      21.0 kPa O2 + 0.03 kPa CO2), the fruits were stored under the following CA
      conditions (kPa O2+kPa CO2): 1+3, 1+5, 2+5, 2+10, and 11+10. In 2011, the fruits
      were stored under CS and CA of 1+0, 1+1, 2+1, and 2+2. The fruit stored under
      different CA conditions had lower respiration and ethylene production, better
      preservation of flesh firmness, texture and titratable acidity, lower skin red
      color, and lower incidence of skin cracking than the fruit in CS. In 2010, the
      fruit under CA with 2+5, 1+5, and 1+3 had a pronounced delay in ripening,
      although it exhibited a high incidence of internal breakdown. In 2011, the CA
      conditions with 2+1 and 2+2 provided the best delay in ripening and a reduced
      incidence of internal breakdown. The best CA condition for cold storage (at 0.5
      degrees C) of 'Laetitia' plums is 2 kPa O2 + 2 kPa CO2. 

PMID- 24676181
TI  - The configuration of the Brazilian scientific field.
AB  - This article describes the configuration of the scientific field in Brazil,
      characterizing the scientific communities in every major area of knowledge in
      terms of installed capacity, ability to train new researchers, and capacity for
      academic production. Empirical data from several sources of information are used
      to characterize the different communities. Articulating the theoretical
      contributions of Pierre Bourdieu, Ludwik Fleck, and Thomas Kuhn, the following
      types of capital are analyzed for each community: social capital (scientific
      prestige), symbolic capital (dominant paradigm), political capital (leadership in
      S & T policy), and economic capital (resources). Scientific prestige is analyzed
      by taking into account the volume of production, activity index, citations, and
      other indicators. To characterize symbolic capital, the dominant paradigms that
      distinguish the natural sciences, the humanities, applied sciences, and
      technology development are analyzed theoretically. Political capital is measured
      by presidency in one of the main agencies in the S & T national system, and
      research resources and fellowships define the economic capital. The article
      discusses the composition of these different types of capital and their
      correspondence to structural capacities in various communities with the aim of
      describing the configuration of the Brazilian scientific field. 

PMID- 24676182
TI  - The challenge of diagnosing tuberculosis in children.

PMID- 24676183
TI  - Accuracy of the QuantiFERON-TB Gold in Tube for diagnosing tuberculosis in a
      young pediatric population previously vaccinated with Bacille Calmette-Guerin .
AB  - OBJECTIVE: To evaluate the accuracy of an interferongamma release assay
      (QuantiFERON-TB Gold in Tube) for diagnosing Mycobacterium tuberculosis infection
      in a young pediatric population. METHODS: 195 children previously vaccinated with
      BCG were evaluated, being 184 healthy individuals with no clinical or
      epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium
      tuberculosis infection, according to clinical, radiological, and laboratory
      parameters. A blood sample was obtained from each child and processed according
      to the manufacturer's instructions. The assay performance was evaluated by a
      Receiver Operating Characteristic (ROC) curve. RESULTS: In the group of 184 non
      infected children, 130 (70.6%) were under the age of four years (mean age of 35
      months). In this group, 177 children (96.2%) had negative test results, six
      (3.2%) had indeterminate results, and one (0.5%) had a positive result. In the
      group of 11 infected children, the mean age was 58.5 months, and two of them
      (18%) had negative results. The ROC curve had an area under the curve of 0.88
      (95%CI 0.82-0.92; p<0.001), disclosing a predictive positive value of 81.8% for
      the test (95%CI 46.3-97.4). The assay sensitivity was 81.8% (95%CI 48.2-97.2) and
      the specificity was 98.8% (95%CI 96-99.8). CONCLUSIONS: In the present study, the
      QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection
      was appropriate in a young pediatric population.

PMID- 24676184
TI  - The training of neonatologists and the paradigms implied in their relationship
      with the parents of babies in the Neonatal Intensive Care Unit.
AB  - OBJECTIVE: To analyze and to interpret the psychological repercussions generated
      by the presence of parents in the Neonatal Intensive Care Unit for residents in
      Neonatology. METHODS: Study based on the psychoanalytic theory, involving a
      methodological interface with qualitative surveys in Health Sciences. Twenty
      resident physicians in Neonatology, from five public institutions of Sao Paulo
      state, responded to a single semi-structured interview. Based on several readings
      of the material, achieving the core of emergent meanings that would be
      significant to the object of the survey, six categories were elected for analysis
      and interpretation: parents' staying at the Neonatal Intensive Care Unit and its
      effects on the neonatologists' professional practice; communication of the
      diagnosis and what parents should know; impasses between parents and doctors when
      the diagnosis is being communicated; doctor's identification with parents;
      communication of the child's death and their participation in the interview.
      RESULTS: The interpretation of the categories provided an understanding of the
      psychic mechanisms mobilized in doctors in their relationships with the
      children's parents, showing that the residents experience anguish and suffering
      when they provide medical care and during their training process, and also that
      they lack psychological support to handle these feelings. CONCLUSIONS: There is a
      need of intervention in neonatologists training and education, which may favor
      the elaboration of daily experiences in the Unit, providing a less anguishing and
      defensive way out for young doctors, especially in their relationship with
      patients and parents.

PMID- 24676185
TI  - Eruption chronology of the first deciduous teeth in children born prematurely
      with birth weight less than 1500 g.
AB  - OBJECTIVE: To describe the eruption chronology of the first deciduous teeth in
      premature infants with birth weight less than 1500 g and to compare it according
      to gender and nutritional status at birth. METHODS: Longitudinal study including
      40 low birth weight premature infants of both genders. The tooth was considered
      erupted when the crown went through the gum and became part of the oral
      environment. The comparison of the eruption chronology in relation to gender and
      among children appropriate or small for gestational age was done by Student's t
      test, being significant p<0.05. RESULTS: The eruption of the first tooth (teeth)
      occurred, on average, with 11.0+/-2.1 months of chronological age and with 9.6+/
      1.9 months corrected for prematurity. The first erupted teeth were the lower
      central incisors. The average eruption for males was 9.7+/-1.9 and, for females,
      9.5+/-1.9 months, both corrected for prematurity (p=0.98). The average eruption
      in children with birth weight appropriate for gestational age was 10.1+/-1.4
      months; for small for gestational age, it was 9.4+/-2.2, also corrected for
      prematurity (p=0.07). CONCLUSIONS: The average eruption age of the first teeth,
      corrected for prematurity, was 9.6 months. Sex and nutritional status at birth
      did not change the eruption chronology.

PMID- 24676186
TI  - Maternal and perinatal aspects of birth defects: a case-control study.
AB  - OBJECTIVE: To assess the prevalence of congenital defects and to investigate
      their maternal and perinatal associated aspects by reviewing Birth Certificates.
      METHODS: Among all born alive infants from January 2003 to December 2007 in
      Maternidade da Santa Casa de Misericordia of Sao Carlos, Southeast Brazil (12,199
      infants), cases were identified as the newborns whose Birth Certificates
      registered any congenital defect. The same sex neonate born immediately after the
      case was chosen as a control. In total, 13 variables were analyzed: six were
      maternal related, three represented labor and delivery conditions and four were
      linked to fetal status. The chi-square and Fisher's exact tests were used to
      compare the variables, being significant p<0.05. RESULTS: The prevalence of
      congenital defects was 0.38% and the association of two or more defects
      represented 32% of all cases. The number of mothers whose education level was
      equal or less than eight years was significantly higher among the group with
      birth defects (p=0.047). A higher frequency of prematurity (p<0.001) and cesarean
      delivery (p=0.004) was observed among children with birth defects. This group
      also showed lower birth weight and Apgar scores in the 1st and the 5th minute
      (p<0.001). CONCLUSIONS: The prevalence of congenital defect of 0.38% is possibly
      due to underreporting. The defects notified in the Birth Certificates were only
      the most visible ones, regardless of their severity. There is a need of adequate
      epidemiological monitoring of birth defects in order to create and expand
      prevention and treatment programs.

PMID- 24676187
TI  - Primary immunodeficiency investigation in patients during and after
      hospitalization in a pediatric intensive care unit.
AB  - OBJECTIVE: To analyze whether the patients with severe infections, admitted in
      the Pediatric Intensive Care Unit of the Hospital de Clinicas of the Universidade
      Federal de Uberlandia, underwent the active screening for primary
      immunodeficiencies (PID). METHODS: Retrospective study that assessed the data
      records of patients with any severe infections admitted in the Pediatric
      Intensive Care Unit, covering a period from January 2011 to January 2012, in
      order to confirm if they performed an initial investigation for PID with blood
      count and immunoglobulin dosage. RESULTS: In the studied period, 53 children were
      hospitalized with severe infections in the Pediatric Intensive Care Unit, and
      only in seven (13.2%) the initial investigation of PID was performed. Among these
      patients, 3/7 (42.8%) showed quantitative alterations in immunoglobulin G (IgG)
      levels, 1/7 (14.3%) had the diagnosis of cyclic neutropenia, and 1/7 (14.3%)
      presented thrombocytopenia and a final diagnosis of Wiskott-Aldrich syndrome.
      Therefore, the PID diagnosis was confirmed in 5/7 (71.4%) of the patients.
      CONCLUSIONS: The investigation of PID in patients with severe infections has not
      been routinely performed in the Pediatric Intensive Care Unit. Our findings
      suggest the necessity of performing PID investigation in this group of patients.

PMID- 24676188
TI  - Consumption of industrialized food by infants attending child day care centers.
AB  - OBJECTIVE: To identify the age of introduction of petit suisse cheese and instant
      noodles in the diet of infants attending nurseries of public day care centers and
      to compare the nutritional composition of these foods with the healthy
      recommended diet (breast milk and salt meal) for this age, in order to estimate
      nutritional errors. METHODS: Cross-sectional study of 366 children (from nine to
      36 months old) who attended day care centers, whose mothers were interviewed
      about the age of introduction of those foods. The means of the nutrients
      indicated on the labels of the most consumed brands were considered. For the
      calculation of the percent composition of breast milk and salt meal, Tables of
      Food Composition were used. To assess the nutritional adequacy, we used the
      Dietary Reference Intakes by age group. The percentage of adequacy evaluation of
      the petit suisse cheese and the instant noodles nutritional compositions was made
      by comparing them with those of the human milk and the salt meal, respectively.
      RESULTS: The petit suisse cheese and the instant noodles were consumed by 89.6
      and 65.3% of the children in the first year of life. The percentages of adequacy
      for carbohydrates were more than twice and the percentages for sodium were 20
      times higher than those found in the recommended foods. CONCLUSIONS: Both
      industrialized products are inappropriate for infants, emphasizing the need for
      adoption of norms that can inform health professionals, educators and parents
      about the risks of consumption.

PMID- 24676189
TI  - Nutritional status of children and adolescents based on body mass index:
      agreement between World Health Organization and International Obesity Task Force.
AB  - OBJECTIVE: To investigate the agreement between two international criteria for
      classification of children and adolescents nutritional status. METHODS: The study
      included 778 girls and 863 boys aged from six to 13 years old. Body mass and
      height were measured and used to calculate the body mass index. Nutritional
      status was classified according to the cut-off points defined by the World Health
      Organization and the International Obesity Task Force. The agreement was
      evaluated using Kappa statistic and weighted Kappa. RESULTS: In order to classify
      the nutritional status, the agreement between the criteria was higher for the
      boys (Kappa 0.77) compared to girls (Kappa 0.61). The weighted Kappa was also
      higher for boys (0.85) in comparison to girls (0.77). Kappa index varied
      according to age. When the nutritional status was classified in only two
      categories--appropriate (thinness + accentuated thinness + eutrophy) and
      overweight (overweight + obesity + severe obesity)--, the Kappa index presented
      higher values than those related to the classification in six categories.
      CONCLUSIONS : A substantial agreement was observed between the criteria, being
      higher in males and varying according to the age.

PMID- 24676190
TI  - Plasma concentrations of retinol in obese children and adolescents: relationship
      to metabolic syndrome components.
AB  - OBJECTIVE: To evaluate obese children and adolescents' retinol plasma levels and
      to correlate them with metabolic syndrome components. METHODS: Cross-sectional
      study with 61 obese children and adolescents (body mass index Z score - ZBMI>+2).
      Pubertal development, arterial blood pressure, body weight and height for
      nutritional classification and waist circumference were obtained. A 15 mL blood
      sample was collected (after a 12-hour fasting in a low luminosity room) for
      retinol determination (cut-off inadequate if <30 ug/dL), lipid profile (HDL-c,
      LDL-c, and triglycerides), oral glucose tolerance test (fasting and 120 minutes)
      and for high sensitivity C-reactive protein. Spearman correlation and multiple
      linear regression were used in the statistical analysis. RESULTS: Mean age was
      10.7+/-2.7 years. There was a predominance of male gender 38/61 (62%) and pre
      pubertal 35/61 (57%) subjects. The average plasmatic retinol was 48.5+/-18.6
      ug/dL. Retinol deficiency and severe obesity were observed in 6/61 (10%) and
      36/61 (59%), respectively. Glucose level at 120 minutes was the independent and
      predictive variable of plasma retinol levels [beta=-0.286 (95%CI -0.013 - 
      0.001)]. CONCLUSIONS: An independent and inverse association between plasma
      retinol levels and glucose tolerance was observed, suggesting an important
      contribution of this vitamin in the morbidities associated to obesity in children
      and adolescents.

PMID- 24676191
TI  - Metabolic syndrome and insulin resistance in obese adolescents.
AB  - OBJECTIVE: To verify the prevalence of metabolic syndrome and insulin resistance
      in obese adolescents and its relationship with different body composition
      indicators. METHODS: A cross-sectional study comprising 79 adolescents aged ten
      to 18 years old. The assessed body composition indicators were: body mass index
      (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The
      metabolic syndrome was diagnosed according to the criteria proposed by Cook et
      al. The insulin resistance was determined by the Homeostasis Model Assessment for
      Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC
      curves was used to assess the BMI and the abdominal circumference, aiming to
      identify the subjects with metabolic syndrome and insulin resistance. The cutoff
      point corresponded to the percentage above the reference value used to diagnose
      obesity. RESULTS: The metabolic syndrome was diagnosed in 45.5% of the patients
      and insulin resistance, in 29.1%. Insulin resistance showed association with HDL
      cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition
      indicators were correlated with insulin resistance (p<0.01). In relation to the
      cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference
      point allowed the identification of insulin resistance and metabolic syndrome.
      The best cutoff point for abdominal circumference to identify insulin resistance
      was 40%. CONCLUSIONS: All body composition indicators, HDL-cholesterol and
      metabolic syndrome showed correlation with insulin resistance. The BMI was the
      most effective anthropometric indicator to identify insulin resistance.

PMID- 24676192
TI  - Body image in different periods of adolescence.
AB  - OBJECTIVE: To analyze body image in different periods of adolescence. METHODS:
      This cross-sectional study enrolled students aged ten to 19 years old of public
      schools in small districts of Minas Gerais, Southeast Brazil. The Body Shape
      Questionnaire (BSQ), the Body Dissatisfaction Assessment Scale for Teenagers and
      the Silhouette Scale for Teenagers (SST) were used. Adolescence phases were
      classified according to the subjects' ages. Weight and height were measured in
      order to calculate the body mass index and the nutritional status. Results were
      analyzed by logistic regression. RESULTS: The study emolled 531 teenagers (318
      females). The average age was 15.6+/-2 .2 years and 84.6% were eutrophic. The
      prevalence of body dissatisfaction varied from 28.9% (BSQ) to 78.9% (SST).
      Overweight adolescents presented greater dissatisfaction (BSQ: OR 3.66, p<0.001;
      SST: OR 4.108, p<0.001). Dissatisfaction also occurred for females and those at
      the early adolescence (p<0.05). CONCLUSIONS: A low prevalence of dissatisfaction
      with the body image was observed among adolescents in small towns of Minas
      Gerais; however, most of them wished a different silhouette than the current one.
      The results showed that younger adolescents had higher dissatisfaction than their
      peers, as well as female and overweighed adolescents.

PMID- 24676193
TI  - Variables associated with family breakdown in healthy and obese/overweigh
      adolescents.
AB  - OBJECTIVE: To evaluate the presence of family breakdown factors among eutrophic
      and overweight/obese adolescents. METHODS: Cross-sectional study of 242 students
      aged between 14 and 19 years old, from a public school. Each student was weighed,
      measured and answered a questionnaire with closed questions addressing the
      presence of family breakdown factors. The adolescents were divided in two groups:
      euthophic and overweight/obese. The answers of both groups were compared by
      Fisher's exact and Mann-Whitney tests. RESULTS: There was no statistically
      significant difference in the prevalence of the studied factors between the two
      groups. Comparing the number of positive answers (presence of family breakdown
      factors) and negative ones (absence of family breakdown factors), no difference
      was observed between the groups. CONCLUSIONS: The inclusion of a control group
      showed that factors of family breakdown, usually identified as associated with
      obesity in adolescents, may also be present in eutrophic adolescents.

PMID- 24676194
TI  - Somatic maturation and body composition in female healthy adolescents with or
      without adjustment for body fat.
AB  - OBJECTIVE: To evaluate the relationship between the stages of somatic maturation
      and body composition in eutrophic female adolescents with or without excessive
      body fat. METHODS: Cross-sectional study of 118 female adolescents, from 14 to 19
      years-old, in Vicosa, Minas Gerais, Southeast Brazil. The adolescents were
      divided in two groups: Group 1 (G1), eutrophic with adequate body fat percentage,
      and Group 2 (G2), eutrophic with high body fat percentage. The somatic maturation
      was assessed by the formula for estimating the Peak Height Velocity (PHV).
      results: The PHV had higher average score in G1 adolescents compared to G2 (0.26
      versus 0.05; p=0.032). There was an association between G1, G2 and the somatic
      maturation (p=0.049). The female adolescents before and during PHV presented
      higher values of fat body BMI (p=0.034) and percentage of central fat (p=0.039)
      compared to the adolescents after PHV. There was a correspondence between before
      PHV stage and the excess of body fat (alpha=0.751). CONCLUSIONS: There was an
      association between somatic maturation and body composition in eutrophic female
      adolescents. Length, BMI and fat percentage were different among the somatic
      maturation stages. It is relevant to evaluate the somatic maturation and the
      changes occurring in the body composition during adolescence in order to better
      evaluate and manage the nutritional status and the body fat excess.

PMID- 24676195
TI  - Inappropriate eating behavior: a longitudinal study with female adolescents.
AB  - OBJECTIVE: To evaluate the inappropriate eating behaviors (IEB) of female
      adolescents over a one-year period. METHODS: 290 adolescents aged between 11 and
      14 years old participated in the three research stages (T1: first four months,
      T2: second four months and T3: third four months). The Eating Attitudes Test (EAT
      26) was applied to assess the IEB. Weight and height were measured to calculate
      body mass index (BMI) in the three study periods. Analysis of variance for
      repeated measures was used to analyze the data, adjusted for the scores of the
      Body Shape Questionnaire and the Brazil Economic Classification Criteria.
      RESULTS: Girls at T1 showed a higher frequency of IEB compared to T2 (p=0.001)
      and T3 (p=0.001). The findings also indicated higher values for BMI in T3 in
      relation to T1 (p=0.04). The other comparisons did not show statistically
      significant differences. CONCLUSIONS: IEB scores of female adolescents declined
      over one year.

PMID- 24676196
TI  - Effects of two programs of exercise on body composition of adolescents with Down
      syndrome.
AB  - OBJECTIVE: To investigate the effects of a 12 week aerobic and resistance
      exercise on body composition of adolescents with Down syndrome. METHODS: A quasi
      experimental study with 41 adolescents with Down syndrome, aged 15.5+/-2.7 years,
      divided into three groups: Aerobic Training Group (ATG; n=16), Resisted Training
      Group (RTG; n=15) and Control Group (CG; n=10). There were two types of training:
      aerobic, with intensity of 50-70% of the heart rate reserve 3 times/week, and
      resisted, with intensity of 12 maximum repetitions 2 times week. Both trainings
      were applied during a 12-week period. The percentage of fat evaluation was
      performed using plethysmography with Bod Pod(r) equipment. Waist circumference
      (WC), body weight and height were also measured. Paired t-test was used to
      compare variables before and after the exercise program. RESULTS: The percentage
      of body fat did not change significantly for both groups that participated in the
      training intervention. However, CG showed a significant increase in this variable
      (31.3+/-7.2 versus 34.0+/-7.9). On the other hand, body mass index (BMI) and WC
      were significantly reduced for ATG (BMI: 27.0+/-4.4 and 26.5+/-4.2; WC: 87.3+/
      11.1 and 86.2+/-9.7), while RTG and GC showed no differences in these variables.
      CONCLUSIONS: The aerobic and resisted training programs maintained body fat
      levels. ATG significantly reduced BMI and WC measures. Individuals who did not
      attend the training intervention increased their percentage of fat.

PMID- 24676197
TI  - Assistance to children in palliative care in the Brazilian scientific literature.
AB  - OBJECTIVE: To describe what has been published in Brazilian scientific literature
      regarding pediatric palliative care. DATA SOURCES: Bibliographic review with a
      descriptive approach. In LILACS and SciELO databases, the descriptors "palliative
      care", "child", "pediatrics", "terminal illness" and "death" were sought, from
      January 2002 to December 2011. The eight selected articles were analyzed
      according to year of publication, type of study, data collected, target
      population, pathology, professionals involved, types of care and main findings.
      DATA SYNTHESIS: Regarding the year of publication, there was an increase in the
      number of publications related to pediatric palliative care. Regarding the type
      of study, four articles were literature reviews and four were qualitative
      researches. Data was collected mainly by semi-structured interviews. The
      participants of the majority of the studies were children's relatives and health
      professionals. The main pathology addressed was cancer and the nurses were the
      most frequently cited professionals. The types of care provided were related to
      physical aspects, general care and psychological, social and spiritual aspects
      (less emphasis). The main findings were: little emphasis on the children's needs,
      the importance of including the family in the care provided and the lack of
      preparation of the health team. CONCLUSIONS: Despite the difficulties and the
      challenges in establishing pediatric palliative care, many articles brought
      important considerations for the development of this practice in the country.

PMID- 24676198
TI  - Family presence during cardiopulmonary resuscitation and invasive procedures in
      children.
AB  - OBJECTIVE: To identify literature evidences related to actions to promote
      family's presence during cardiopulmonary resuscitation and invasive procedures in
      children hospitalized in pediatric and neonatal critical care units. DATA
      SOURCES: Integrative literature review in PubMed, SciELO and Lilacs databases,
      from 2002 to 2012, with the following inclusion criteria: research article in
      Medicine, or Nursing, published in Portuguese, English or Spanish, using the
      keywords "family", "invasive procedures", "cardiopulmonary resuscitation",
      "health staff", and "Pediatrics". Articles that did not refer to the presence of
      the family in cardiopulmonary resuscitation and invasive procedures were
      excluded. Therefore, 15 articles were analyzed. DATA SYNTHESIS: Most articles
      were published in the United States (80%), in Medicine and Nursing (46%), and
      were surveys (72%) with healthcare team members (67%) as participants. From the
      critical analysis, four themes related to the actions to promote family's
      presence in invasive procedures and cardiopulmonary resuscitation were obtained:
      a) to develop a sensitizing program for healthcare team; b) to educate the
      healthcare team to include the family in these circumstances; c) to develop a
      written institutional policy; d) to ensure the attendance of family's needs.
      CONCLUSIONS: Researches on these issues must be encouraged in order to help
      healthcare team to modify their practice, implementing the principles of the
      Patient and Family Centered Care model, especially during critical episodes.

PMID- 24676199
TI  - Asthma in children and adolescents in Brazil: contribution of the International
      Study of Asthma and Allergies in Childhood (ISAAC).
AB  - OBJECTIVE: To assess asthma among Brazilian pediatric population applying the
      International Study of Asthma and Allergies in Childhood (ISAAC), an
      internationally standardized and validated protocol. DATA SOURCES: ISAAC was
      conceived to maximize the value of epidemiologic studies on asthma and allergic
      diseases, establishing a standardized method (self-applicable written
      questionnaire and/or video questionnaire) capable to facilitate the international
      collaboration. Designed to be carried out in three successive and dependent
      phases, the ISAAC gathered a casuistic hitherto unimaginable in the world and in
      Brazil. This review included data gathered from ISAAC official Brazilian centers
      and others who used this method. DATA SYNTHESIS: At the end of the first phase,
      it has been documented that the prevalence of asthma among Brazilian
      schoolchildren was the eighth among all centers participating all over the world.
      Few centers participated in the second phase and investigated possible
      etiological factors, especially those suggested by the first phase, and brought
      forth many conjectures. The third phase, repeated seven years later, assessed the
      evolutionary trend of asthma and allergic diseases prevalence in centers that
      participated simultaneously in phases I and III and in other centers not involved
      in phase I. CONCLUSIONS: In Brazil, the ISAAC study showed that asthma is a
      disease of high prevalence and impact in children and adolescents and should be
      seen as a Public Health problem. Important regional variations, not well
      understood yet, and several risk factors were found, which makes us wonder: is
      there only one or many asthmas in Brazil?

PMID- 24676200
TI  - Selenium deficiency and the effects of supplementation on preterm infants.
AB  - OBJECTIVE: This study aimed to review the literature about blood concentrations
      of selenium associated with gestational age, feeding, supplementation and related
      clinical features in preterm infants. DATA SOURCES: Systematic review in the
      following databases: MEDLINE, PubMed, Google academics, SciELO. org,
      ScienceDirect (Elsevier) and CINAHL-Plus with Full Text (EBSCO). Articles
      published up to January 2013 with the keywords "selenium deficiency", "selenium
      supplementation", "neonates", "infants", "newborn" and "preterm infants" were
      selected. DATA SYNTHESIS: The studies reported that low blood selenium levels are
      associated with increased risk of respiratory diseases. Preterm infants,
      especially with low birth weight, presented lower selenium levels. Selenium
      deficiency has also been associated with the use of oral infant formula, enteral
      and parenteral nutrition (with or without selenium addition). The optimal dose
      and length of selenium supplementation is not well-established, since they are
      based only on age group and selenium ingestion by breastfed children.
      Furthermore, the clinical status of the infant affected by conditions that may
      increase oxidative stress, and consequently, selenium requirements is not taken
      into account. CONCLUSIONS: Prematurity and low birth weight can contribute to low
      blood selenium in premature infants. Selenium supplementation seems to minimize
      or prevent clinical complications caused by prematurity.

PMID- 24676201
TI  - Telehealth application on the rehabilitation of children and adolescents.
AB  - OBJECTIVE: To systematically review the literature on the telehealth initiatives
      in telerehabilitation practices in children and adolescents from zero to 18 years
      old. DATA SOURCES: Randomized and controlled clinical trials published in the
      past ten years (January 2002 to February 2012) in Medline/PubMed, Medline/BVS,
      PEDro and Cochrane Library databases. The descriptors "telemedicine",
      "rehabilitation" and "telehealth" were used in three different languages
      (English, Portuguese and Spanish). DATA SYNTHESIS: From the 20 studies found in
      the literature, nine were included in this review. Most of the studies showed
      that telerehabilitation is able to produce better results in the treatment when
      compared to the traditional methods, providing less frequency of symptoms, better
      disease control, better quality of life and greater adherence to treatment.
      CONCLUSIONS: Telerehabilitation is a viable and effective strategy in the
      treatment of common diseases in children and adolescents. However, there are few
      studies on the subject in this age group. Although telehealth is already
      consolidated worldwide, there are no studies in Brazil that used the
      telerehabilitation in children and adolescents, which reinforces the need for
      more research and investments.

PMID- 24676202
TI  - Acute liver failure in a term neonate after repeated paracetamol administration.
AB  - OBJECTIVE: Severe hepatotoxicity caused by paracetamol is rare in neonates. We
      report a case of paracetamol-induced acute liver failure in a term neonate. CASE
      DESCRIPTION: A 26-day-old boy was admitted with intestinal bleeding, shock signs,
      slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate:
      7.1 mEq/L), hypoglycemia (18 mg/dL), increased serum aminotransferase activity
      (AST=4,039 IU/L; ALT=1,087 IU/L) and hyperbilirubinemia (total: 9.57 mg/dL;
      direct: 6.18 mg/dL) after receiving oral paracetamol (10 mg/kg/dose every 4
      hours) for three consecutive days (total dose around 180 mg/kg; serum
      concentration 36-48 hours after the last dose of 77 ug/ mL). Apart from
      supportive measures, the patient was successfully treated with intravenous N
      acetylcysteine infusion during 11 consecutive days, and was discharged on day 34.
      The follow-up revealed full recovery of clinical and of laboratory findings of
      hepatic function. COMMENTS: The paracetamol pharmacokinetics and pharmacodynamics
      in neonates and infants differ substantially from those in older children and
      adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system
      and the increased ability to synthesize glutathione--which provides greater
      resistance after overdoses--, it is possible to produce hepatotoxic metabolites
      (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione
      sources are depleted. Paracetamol clearance is reduced and the half-life of
      elimination is prolonged. Therefore, a particular dosing regimen should be
      followed due to the toxicity risk of cumulative doses. This report highlights the
      risk for severe hepatotoxicity in neonates after paracetamol multiple doses for
      more than two to three days.

PMID- 24676203
TI  - Age-specific mortality during the 1918-19 influenza pandemic and possible
      relationship to the 1889-92 influenza pandemic.

PMID- 24676205
TI  - Reply to Wilson et al.

PMID- 24676204
TI  - Distinct cross-reactive B-cell responses to live attenuated and inactivated
      influenza vaccines.
AB  - BACKGROUND: The immunological bases for the efficacies of the 2 currently
      licensed influenza vaccines, live attenuated influenza vaccine (LAIV) and
      inactivated influenza vaccine (IIV), are not fully understood. The goal of this
      study was to identify specific B-cell responses correlated with the known
      efficacies of these 2 vaccines. METHODS: We compared the B-cell and antibody
      responses after immunization with 2010/2011 IIV or LAIV in young adults, focusing
      on peripheral plasmablasts 6-8 days after vaccination. RESULTS: The quantities of
      vaccine-specific plasmablasts and plasmablast-derived polyclonal antibodies
      (PPAbs) in IIV recipients were significantly higher than those in LAIV
      recipients. No significant difference was detected in the avidity of vaccine
      specific PPAbs between the 2 vaccine groups. Proportionally, LAIV induced a
      greater vaccine-specific immunoglobulin A plasmablast response, as well as a
      greater plasmablast response to the conserved influenza nuclear protein, than
      IIV. The cross-reactive plasmablast response to heterovariant strains, as
      indicated by the relative levels of cross-reactive plasmablasts and the cross
      reactive PPAb binding reactivity, was also greater in the LAIV group.
      CONCLUSIONS: Distinct quantitative and qualitative patterns of plasmablast
      responses were induced by LAIV and IIV in young adults; a proportionally greater
      cross-reactive response was induced by LAIV.

PMID- 24676206
TI  - Influenza vaccine in the red zone defense: a game-day player.

PMID- 24676207
TI  - Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed
      influenza illness in US children, 2010-2012.
AB  - BACKGROUND: No studies have examined the effectiveness of influenza vaccine
      against intensive care unit (ICU) admission associated with influenza virus
      infection among children. METHODS: In 2010-2011 and 2011-2012, children aged 6
      months to 17 years admitted to 21 US pediatric intensive care units (PICUs) with
      acute severe respiratory illness and testing positive for influenza were enrolled
      as cases; children who tested negative were PICU controls. Community controls
      were children without an influenza-related hospitalization, matched to cases by
      comorbidities and geographic region. Vaccine effectiveness was estimated with
      logistic regression models. RESULTS: We analyzed data from 44 cases, 172 PICU
      controls, and 93 community controls. Eighteen percent of cases, 31% of PICU
      controls, and 51% of community controls were fully vaccinated. Compared to
      unvaccinated children, children who were fully vaccinated were 74% (95% CI, 19%
      to 91%) or 82% (95% CI, 23% to 96%) less likely to be admitted to a PICU for
      influenza compared to PICU controls or community controls, respectively. Receipt
      of 1 dose of vaccine among children for whom 2 doses were recommended was not
      protective. CONCLUSIONS: During the 2010-2011 and 2011-2012 US influenza seasons,
      influenza vaccination was associated with a three-quarters reduction in the risk
      of life-threatening influenza illness in children.

PMID- 24676208
TI  - Association between antibody titers and protection against influenza virus
      infection within households.
AB  - BACKGROUND: Previous studies have established that antibody titer measured by the
      hemagglutination-inhibiting (HAI) assay is correlated with protection against
      influenza virus infection, with an HAI titer of 1:40 generally associated with
      50% protection. METHODS: We recruited index cases with confirmed influenza virus
      infection from outpatient clinics, and followed up their household contacts for 7
      10 days to identify secondary infections. Serum samples collected from a subset
      of household contacts were tested by HAI and microneutralization (MN) assays
      against prevalent influenza viruses. We analyzed the data using an individual
      hazard-based transmission model that adjusted for age and vaccination history.
      RESULTS: Compared to a reference group with antibody titers <1:10, we found that
      HAI titers of 1:40 against influenza A(H1N1) and A(H3N2) were associated with 31%
      (95% confidence interval [CI], 13%-46%) and 31% (CI, 1%-53%) protection against
      polymerase chain reaction (PCR)-confirmed A(H1N1) and A(H3N2) virus infection,
      respectively, while an MN titer of 1:40 against A(H3N2) was associated with 49%
      (95% CI, 7%-81%) protection against PCR-confirmed A(H3N2) virus infection.
      CONCLUSIONS: An HAI titer of 1:40 was associated with substantially less than 50%
      protection against PCR-confirmed influenza virus infection within households,
      perhaps because of exposures of greater duration or intensity in that confined
      setting.

PMID- 24676209
TI  - Effects of glucocorticoid exposure on growth and structural maturation of the
      heart of the preterm piglet.
AB  - Inadequate maintenance of systemic blood flow in neonates following preterm birth
      is associated with increased morbidity and mortality, and may be due in part to
      structural immaturity of the myocardium. Maternal glucocorticoid administration
      is associated with improved cardiovascular function, and possibly promotes
      structural maturation of the myocardium. This study assessed the structural
      maturity of the myocardium in male and female preterm and term piglets, and
      preterm piglets exposed to a regimen of maternal glucocorticoids as used
      clinically. In preterm, term and glucocorticoid exposed preterm piglets
      cardiomyocyte maturity was examined by measuring the proportion of binucleated
      myocytes and the volumes of single living ventricular cardiomyocytes with
      fluorescence microscopy. Ventricular apoptosis and proliferation were measured by
      immunohistochemistry. Preterm piglet hearts had fewer binucleated myocytes,
      smaller myocytes, and more proliferative and fewer apoptotic nuclei than term
      hearts. Maternal glucocorticoid treatment resulted in increased binucleation with
      no increase in myocyte volume, and levels of proliferation and apoptosis that
      were more similar to the term heart. Atrial weights were increased and in female
      piglets there was an increase in the ratio of left to right ventricular weight.
      The observed changes in atrial mass and myocyte structural maturation correlated
      with changes in cardiac function of isolated hearts of littermates. In
      conclusion, the association between increased myocardial maturation following
      glucocorticoid exposure, improved cardiac function in littermates, and clinical
      improvement in human neonatal cardiac function exposed to antenatal
      glucocorticoids, suggests that glucocorticoid exposure contributes to improved
      cardiovascular function in preterm infants by promoting myocardial structural
      maturity. 

PMID- 24676210
TI  - Designing and piloting a program to provide water filters and improved cookstoves
      in Rwanda.
AB  - BACKGROUND: In environmental health interventions addressing water and indoor air
      quality, multiple determinants contribute to adoption. These may include
      technology selection, technology distribution and education methods, community
      engagement with behavior change, and duration and magnitude of implementer
      engagement. In Rwanda, while the country has the fastest annual reduction in
      child mortality in the world, the population is still exposed to a disease burden
      associated with environmental health challenges. Rwanda relies both on direct
      donor funding and coordination of programs managed by international non-profits
      and health sector businesses working on these challenges. METHODS AND FINDINGS:
      This paper describes the design, implementation and outcomes of a pilot program
      in 1,943 households across 15 villages in the western province of Rwanda to
      distribute and monitor the use of household water filters and improved
      cookstoves. Three key program design criteria include a.) an investment in
      behavior change messaging and monitoring through community health workers, b.)
      free distributions to encourage community-wide engagement, and c.) a private
      public partnership incentivized by a business model designed to encourage "pay
      for performance". Over a 5-month period of rigorous monitoring, reported uptake
      was maintained at greater than 90% for both technologies, although exclusive use
      of the stove was reported in only 28.5% of households and reported water volume
      was 1.27 liters per person per day. On-going qualitative monitoring suggest
      maintenance of comparable adoption rates through at least 16 months after the
      intervention. CONCLUSION: High uptake and sustained adoption of a water filter
      and improved cookstove was measured over a five-month period with indications of
      continued comparable adoption 16 months after the intervention. The design
      attributes applied by the implementers may be sufficient in a longer term. In
      particular, sustained and comprehensive engagement by the program implementer is
      enabled by a pay-for-performance business model that rewards sustained behavior
      change.

PMID- 24676211
TI  - Mechanism of MU-conotoxin PIIIA binding to the voltage-gated Na+ channel NaV1.4.
AB  - Several subtypes of voltage-gated Na+ (NaV) channels are important targets for
      pain management. MU-Conotoxins isolated from venoms of cone snails are potent and
      specific blockers of different NaV channel isoforms. The inhibitory effect of MU
      conotoxins on NaV channels has been examined extensively, but the mechanism of
      toxin specificity has not been understood in detail. Here the known structure of
      MU-conotoxin PIIIA and a model of the skeletal muscle channel NaV1.4 are used to
      elucidate elements that contribute to the structural basis of MU-conotoxin
      binding and specificity. The model of NaV1.4 is constructed based on the crystal
      structure of the bacterial NaV channel, NaVAb. Six different binding modes, in
      which the side chain of each of the basic residues carried by the toxin protrudes
      into the selectivity filter of NaV1.4, are examined in atomic detail using
      molecular dynamics simulations with explicit solvent. The dissociation constants
      (Kd) computed for two selected binding modes in which Lys9 or Arg14 from the
      toxin protrudes into the filter of the channel are within 2 fold; both values in
      close proximity to those determined from dose response data for the block of NaV
      currents. To explore the mechanism of PIIIA specificity, a double mutant of
      NaV1.4 mimicking NaV channels resistant to MU-conotoxins and tetrodotoxin is
      constructed and the binding of PIIIA to this mutant channel examined. The double
      mutation causes the affinity of PIIIA to reduce by two orders of magnitude. 

PMID- 24676213
TI  - Beneficial effects of Astragaloside IV for hair loss via inhibition of Fas/Fas L
      mediated apoptotic signaling.
AB  - Apoptosis with premature termination of hair follicle growth induces several
      types of hair loss and is one of the crucial factors of hair loss. Astragaloside
      IV, which is a major component of Astragalus membranaceus, is a cycloartane
      triterpene saponin. Although an anti-apoptotic effect of Astragaloside IV has
      been reported, its effects against hair loss have not been investigated. To
      explore the underlying mechanisms of Astragaloside IV on apoptotic signaling in
      hair follicle, the dorsal skin of depilated C57BL/6 mice was topically treated
      with 1 and 100 MUM Astragaloside IV for 14 days. In Astragaloside IV-treated
      group, TUNEL-positive cells were reduced. We found that Astragaloside IV blocked
      the procaspase-8, resulting in the inhibition of caspase-3 and procaspase-9
      activities. The changes were accompanied with down-regulation of Bax and p53, and
      up-regulation of Bcl-2 and Bcl-xL by Astragaloside IV treatment. In addition,
      activation of NF-kappaB and phosphorylation of IkappaB-alpha were inhibited,
      along with decreases in three MAPKs: ERK, SAPK/JNK and p38 by Astragaloside IV.
      The expressions of KGF, p21, TNF-alpha and IL-1beta, which are keratinocyte
      terminal differentiation markers associated with catagen, were modulated by
      treatment with Astragaloside IV. These results demonstrated that Astragaloside IV
      is concerned with blocking the Fas/Fas L-mediated apoptotic pathway, which would
      be an alternative therapy for hair loss. 

PMID- 24676212
TI  - Dispersal of adult culex mosquitoes in an urban west nile virus hotspot: a mark
      capture study incorporating stable isotope enrichment of natural larval habitats.
AB  - Dispersal is a critical life history behavior for mosquitoes and is important for
      the spread of mosquito-borne disease. We implemented the first stable isotope
      mark-capture study to measure mosquito dispersal, focusing on Culex pipiens in
      southwest suburban Chicago, Illinois, a hotspot of West Nile virus (WNV)
      transmission. We enriched nine catch basins in 2010 and 2011 with 15N-potassium
      nitrate and detected dispersal of enriched adult females emerging from these
      catch basins using CDC light and gravid traps to distances as far as 3 km. We
      detected 12 isotopically enriched pools of mosquitoes out of 2,442 tested during
      the two years and calculated a mean dispersal distance of 1.15 km and maximum
      flight range of 2.48 km. According to a logistic distribution function, 90% of
      the female Culex mosquitoes stayed within 3 km of their larval habitat, which
      corresponds with the distance-limited genetic variation of WNV observed in this
      study region. This study provides new insights on the dispersal of the most
      important vector of WNV in the eastern United States and demonstrates the utility
      of stable isotope enrichment for studying the biology of mosquitoes in other
      disease systems. 

PMID- 24676214
TI  - Prediction of multi-type membrane proteins in human by an integrated approach.
AB  - Membrane proteins were found to be involved in various cellular processes
      performing various important functions, which are mainly associated to their
      types. However, it is very time-consuming and expensive for traditional
      biophysical methods to identify membrane protein types. Although some
      computational tools predicting membrane protein types have been developed, most
      of them can only recognize one kind of type. Therefore, they are not as effective
      as one membrane protein can have several types at the same time. To our
      knowledge, few methods handling multiple types of membrane proteins were
      reported. In this study, we proposed an integrated approach to predict multiple
      types of membrane proteins by employing sequence homology and protein-protein
      interaction network. As a result, the prediction accuracies reached 87.65%,
      81.39% and 70.79%, respectively, by the leave-one-out test on three datasets. It
      outperformed the nearest neighbor algorithm adopting pseudo amino acid
      composition. The method is anticipated to be an alternative tool for identifying
      membrane protein types. New metrics for evaluating performances of methods
      dealing with multi-label problems were also presented. The program of the method
      is available upon request. 

PMID- 24676215
TI  - Distribution of hydrothermal Alvinocaridid shrimps: effect of geomorphology and
      specialization to extreme biotopes.
AB  - The aim of this study is to review of our knowledge about distribution of
      recently known species of vent shrimps and to analyze factors influencing
      distribution patterns. Analyses are based upon (1) original material taken during
      eight cruises in the Atlantic Ocean (a total of 5861 individuals) and (2)
      available literature data from the Atlantic, Pacific, and Indian Oceans. Vent
      shrimps have two patterns of the species ranges: local (single vent site) and
      regional (three--six vent sites). Pacific species ranges are mainly of the local
      type and the Atlantic species ranges are of the regional type. The regional type
      of species ranges may be associated with channels providing easy larval dispersal
      (rift valleys, trenches), while the local type is characteristic for other areas.
      Specialization of a shrimp genus to extreme vent habitats leads to two effects:
      (1) an increase in the number of vent fields inhabited by the genus and (2) a
      decrease of species number within the genus.

PMID- 24676217
TI  - Impact of an electronic health record operating room management system in
      ophthalmology on documentation time, surgical volume, and staffing.
AB  - IMPORTANCE: Although electronic health record (EHR) systems have potential
      benefits, such as improved safety and quality of care, most ophthalmology
      practices in the United States have not adopted these systems. Concerns persist
      regarding potential negative impacts on clinical workflow. In particular, the
      impact of EHR operating room (OR) management systems on clinical efficiency in
      the ophthalmic surgery setting is unknown. OBJECTIVE: To determine the impact of
      an EHR OR management system on intraoperative nursing documentation time,
      surgical volume, and staffing requirements. DESIGN, SETTING, AND PARTICIPANTS:
      For documentation time and circulating nurses per procedure, a prospective cohort
      design was used between January 10, 2012, and January 10, 2013. For surgical
      volume and overall staffing requirements, a case series design was used between
      January 29, 2011, and January 28, 2013. This study involved ophthalmic OR nurses
      (n = 13) and surgeons (n = 25) at an academic medical center. EXPOSURES:
      Electronic health record OR management system implementation. MAIN OUTCOMES AND
      MEASURES: (1) Documentation time (percentage of operating time documenting
      [POTD], absolute documentation time in minutes), (2) surgical volume
      (procedures/time), and (3) staffing requirements (full-time equivalents,
      circulating nurses/procedure). Outcomes were measured during a baseline period
      when paper documentation was used and during the early (first 3 months) and late
      (4-12 months) periods after EHR implementation. RESULTS: There was a worsening in
      total POTD in the early EHR period (83%) vs paper baseline (41%) (P < .001). This
      improved to baseline levels by the late EHR period (46%, P = .28), although POTD
      in the cataract group remained worse than at baseline (64%, P < .001). There was
      a worsening in absolute mean documentation time in the early EHR period (16.7
      minutes) vs paper baseline (7.5 minutes) (P < .001). This improved in the late
      EHR period (9.2 minutes) but remained worse than in the paper baseline (P <
      .001). While cataract procedures required more circulating nurses in the early
      EHR (mean, 1.9 nurses/procedure) and late EHR (mean, 1.5 nurses/procedure)
      periods than in the paper baseline (mean, 1.0 nurses/procedure) (P < .001),
      overall staffing requirements and surgical volume were not significantly
      different between the periods. CONCLUSIONS AND RELEVANCE: Electronic health
      record OR management system implementation was associated with worsening of
      intraoperative nursing documentation time especially in shorter procedures.
      However, it is possible to implement an EHR OR management system without serious
      negative impacts on surgical volume and staffing requirements.

PMID- 24676216
TI  - Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by
      whole-genome plasma DNA sequencing.
AB  - Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), such
      as cetuximab and panitumumab, have evolved to important therapeutic options in
      metastatic colorectal cancer (CRC). However, almost all patients with clinical
      response to anti-EGFR therapies show disease progression within a few months and
      little is known about mechanism and timing of resistance evolution. Here we
      analyzed plasma DNA from ten patients treated with anti-EGFR therapy by whole
      genome sequencing (plasma-Seq) and ultra-sensitive deep sequencing of genes
      associated with resistance to anti-EGFR treatment such as KRAS, BRAF, PIK3CA, and
      EGFR. Surprisingly, we observed that the development of resistance to anti-EGFR
      therapies was associated with acquired gains of KRAS in four patients (40%),
      which occurred either as novel focal amplifications (n = 3) or as high level
      polysomy of 12p (n = 1). In addition, we observed focal amplifications of other
      genes recently shown to be involved in acquired resistance to anti-EGFR
      therapies, such as MET (n = 2) and ERBB2 (n = 1). Overrepresentation of the EGFR
      gene was associated with a good initial anti-EGFR efficacy. Overall, we
      identified predictive biomarkers associated with anti-EGFR efficacy in seven
      patients (70%), which correlated well with treatment response. In contrast, ultra
      sensitive deep sequencing of KRAS, BRAF, PIK3CA, and EGFR did not reveal the
      occurrence of novel, acquired mutations. Thus, plasma-Seq enables the
      identification of novel mutant clones and may therefore facilitate early
      adjustments of therapies that may delay or prevent disease progression.

PMID- 24676218
TI  - Testing the stem dominance hypothesis: meaning analysis of inflected words and
      prepositional phrases.
AB  - We tested the hypothesis that lexical-semantic access of inflected words is
      governed by the word stem. Object drawings overlaid with a dot/arrow marking
      position/movement were matched with corresponding linguistic expressions like
      "from the house". To test whether the stem dominates lexical-semantic access
      irrespective of its position, we used Swedish prepositional phrases (locative
      information via preposition immediately preceding the stem) or Finnish case
      inflected words (locative information via suffix immediately following the stem).
      Both in monolingual Swedish and in bilingual Finnish-Swedish speakers, correct
      stems with incorrect prepositions/case-endings were hardest to reject. This
      finding supports the view that the stem is indeed the dominant unit in meaning
      access of inflected words. 

PMID- 24676220
TI  - Dietary interventions and blood pressure in Latin America - systematic review and
      meta-analysis.
AB  - BACKGROUND: High blood pressure is the major risk factor for cardiovascular
      disease. Low blood pressure control rates in Latin American populations emphasize
      the need for gathering evidence on effective therapies. OBJECTIVE: To evaluate
      the effects of dietary interventions on blood pressure in Latin American
      populations. METHODS: Systematic review. Electronic databases (MEDLINE/PubMed,
      Embase, Cochrane Library, CINAHL, Web of Science, Scopus, SciELO, LILACS and VHL)
      were searched and manual search for studies published up to April 2013 was
      performed. Parallel studies about dietary interventions in Latin American adult
      populations assessing arterial blood pressure (mm Hg) before and after
      intervention were included. RESULTS: Of the 405 studies identified, 10 randomized
      controlled trials were included and divided into 3 subgroups according to the
      proposed dietary intervention. There was a non-significant reduction in systolic
      blood pressure in the subgroups of mineral replacement (-4.82; 95% CI: -11.36 to
      1.73) and complex pattern diets (-3.17; 95% CI: -7.62 to 1.28). Regarding
      diastolic blood pressure, except for the hyperproteic diet subgroup, all
      subgroups showed a significant reduction in blood pressure: -4.66 mmHg (95% CI: 
      9.21 to -0.12) and -4.55 mmHg (95% CI: -7.04 to -2.06) for mineral replacement
      and complex pattern diets, respectively. CONCLUSION: Available evidence on the
      effects of dietary changes on blood pressure in Latin American populations
      indicates a homogeneous effect of those interventions, although not significant
      for systolic blood pressure. Samples were small and the quality of the studies
      was generally low. Larger studies are required to build robust evidence.

PMID- 24676219
TI  - Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy
      in colonized epithelial multilayer cultures.
AB  - There is a pressing need for modeling of the symbiotic and at times dysbiotic
      relationship established between bacterial microbiomes and human mucosal
      surfaces. In particular clinical studies have indicated that the complex vaginal
      microbiome (VMB) contributes to the protection against sexually-transmitted
      pathogens including the life-threatening human immunodeficiency virus (HIV-1).
      The human microbiome project has substantially increased our understanding of the
      complex bacterial communities in the vagina however, as is the case for most
      microbiomes, very few of the community member species have been successfully
      cultivated in the laboratory limiting the types of studies that can be completed.
      A genetically controlled ex vivo model system is critically needed to study the
      complex interactions and associated molecular dialog. We present the first
      vaginal mucosal culture model that supports colonization by both healthy and
      dysbiotic VMB from vaginal swabs collected from routine gynecological patients.
      The immortalized vaginal epithelial cells used in the model and VMB
      cryopreservation methods provide the opportunity to reproducibly create
      replicates for lab-based evaluations of this important mucosal/bacterial
      community interface. The culture system also contains HIV-1 susceptible cells
      allowing us to study the impact of representative microbiomes on replication. Our
      results show that our culture system supports stable and reproducible
      colonization by VMB representing distinct community state types and that the
      selected representatives have significantly different effects on the replication
      of HIV-1. Further, we show the utility of the system to predict unwanted
      alterations in efficacy or bacterial community profiles following topical
      application of a front line antiretroviral. 

PMID- 24676223
TI  - Stress alone or associated with ethanol induces prostanoid release in rat aorta
      via alpha2-Adrenoceptor.
AB  - BACKGROUND: Stress and ethanol are both, independently, important cardiovascular
      risk factors. OBJECTIVE: To evaluate the cardiovascular risk of ethanol
      consumption and stress exposure, isolated and in association, in male adult rats.
      METHODS: Rats were separated into 4 groups: Control, ethanol (20% in drinking
      water for 6 weeks), stress (immobilization 1h day/5 days a week for 6 weeks) and
      stress/ethanol. Concentration-responses curves to noradrenaline - in the absence
      and presence of yohimbine, L-NAME or indomethacin - or to phenylephrine were
      determined in thoracic aortas with and without endothelium. EC50 and maximum
      response (n=8-12) were compared using two-way ANOVA/Bonferroni method. RESULTS:
      Either stress or stress in association with ethanol consumption increased the
      noradrenaline maximum responses in intact aortas. This hyper-reactivity was
      eliminated by endothelium removal or by the presence of either indomethacin or
      yohimbine, but was not altered by the presence of L-NAME. Meanwhile, ethanol
      consumption did not alter the reactivity to noradrenaline. The phenylephrine
      responses in aortas both with and without endothelium also remained unaffected
      regardless of protocol. CONCLUSION: Chronic stress increased rat aortic responses
      to noradrenaline. This effect is dependent upon the vascular endothelium and
      involves the release of vasoconstrictor prostanoids via stimulation of
      endothelial alpha-2 adrenoceptors. Moreover, chronic ethanol consumption appeared
      to neither influence noradrenaline responses in rat thoracic aorta, nor did it
      modify the increase of such responses observed as a consequence of stress
      exposure.

PMID- 24676224
TI  - Excess weight, anthropometric variables and blood pressure in schoolchildren aged
      10 to 18 years.
AB  - BACKGROUND: The prevalence of hypertension among children and adolescents is
      estimated to range between 1% and 13%. Excess weight and central obesity are
      related to blood pressure levels in adults, and may be important in the early
      pathogenesis of SH when present in childhood. OBJECTIVES: To study the
      association between anthropometric variables and blood pressure levels in
      schoolchildren from the 5th and 8th grades, and to identify which parameter was
      more strongly correlated with blood pressure levels. METHODS: Contemporary cross
      sectional study with probabilistic population-based cluster sampling of
      schoolchildren enrolled from the 5th to the 8th grades in public elementary
      schools of Porto Alegre. Data on familial risk factors and anthropometry were
      collected. Statistical analysis included correlations and cluster-adjusted
      confidence intervals. RESULTS: The mean age of participants was 12.57 (+/- 1.64)
      years, and 55.2% of them were females. Abnormal blood pressure levels were found
      in 11.3% of the sample and borderline values, in 16.2%. Among the anthropometric
      variables analyzed, hip circumference was the one with the strongest correlation
      with increased blood pressure (r = 0.462, p < 0.001), followed by waist
      circumference (r = 0.404, p < 0.001) and abdominal skinfold (r = 0.291, p <
      0.001). CONCLUSION: We observed an association of waist circumference and
      skinfolds with increased blood pressure levels in the schoolchildren of the
      sample. Therefore, it is of the utmost importance that early measurements of
      blood pressure, and waist and hip circumferences become a routine in health
      services in order to prevent this condition.

PMID- 24676225
TI  - Short-term thyroid hormone excess affects the heart but does not affect adrenal
      activity in rats.
AB  - BACKGROUND: Hyperthyroidism (Hy) exerts a broad range of influences on a variety
      of physiological parameters. Its disruptive effect on cardiovascular system is
      one of its most remarkable impacts. Moreover, Hy has been clinically associated
      with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis.
      OBJECTIVE: Evaluate the impact of short-term Hy on cardiac performance and
      adrenal activity of rats. METHODS: Induction of Hy in Wistar rats through
      injections of T3 (150 ug/kg) for 10 days (hyperthyroid group - HG) or vehicle
      (control group). The cardiovascular performance was evaluated by:
      echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of
      isolated papillary muscles (IPM) and direct measurement of blood pressures.
      Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24
      hour fecal corticosterone (FC) levels on the, 5th and 10th days of T3 treatment.
      RESULTS: In HG, the ECHO showed reduction of the End Systolic and End Diastolic
      Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and
      Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output
      increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the
      maximum rate of force decay during relaxation was higher in all extracellular
      calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p <=
      0.05). On the other hand, there was no difference in the adrenal weight/body
      weight ratio or in the 24-hour FC levels. CONCLUSIONS: Hy induces positive
      inotropic, chronotropic and lusitropic effects on the heart by direct effects of
      T3 and increases SBP. Those alterations are not correlated with changes in the
      adrenal activity.

PMID- 24676226
TI  - Prevalence of metabolic syndrome in elderly and agreement among four diagnostic
      criteria.
AB  - BACKGROUND: Metabolic syndrome (MS) is an aggregation of risk factors that
      increase the incidence of cardiovascular events and diabetes mellitus (DM).
      Population aging is accompanied by higher prevalence of MS, which varies
      depending on the population studied and the diagnostic criteria used. OBJECTIVE:
      To determine prevalence of MS in the elderly using four diagnostic criteria and
      agreement between them. METHODS: Cross-sectional study on 243 patients older than
      60 years (180 women) in Niteroi, RJ. They were evaluated by clinical examination,
      fasting glucose, fasting insulin, lipid profile and anthropometric measurements -
      weight, height, waist circumference and waist/hip ratio. Prevalence of MS was
      estimated by World Health Organization (WHO) modified, National Cholesterol
      Education Program - Adult Treatment Panel III (NCEP-ATP III), International
      Diabetes Federation (IDF) and Joint Interim Statement (JIS) criteria. RESULTS:
      Prevalence was high with the four criteria WHO (51.9%), NCEP-ATPIII (45.2%), IDF
      (64.1%) and JIS (69.1%), and agreement between criteria by kappa was moderate in
      almost all comparisons WHO vs. IDF (k = 0.47;95% confidence interval (CI), 0.35
      to 0.58); WHO vs. NCEP-ATPIII (k = 0.51; 95% CI, 0.40 to 0.61); WHO vs. JIS (k =
      0.45; 95% CI, 0.33 to 0.56); IDF vs. NCEP-ATPIII (k = 0.55; 95% CI, 0.45 to 0.65)
      and NCEP-ATPIII vs. JIS (k = 0.53; 95% CI, 0.43-0.64), except between IDF vs. JIS
      (K = 0.89;95% CI, 0.83 to 0.95), which was considered good. CONCLUSION:
      Prevalence of MS was high with the four diagnostic criteria, mainly by JIS. There
      was good agreement between JIS and IDF criteria and moderate among the others.

PMID- 24676227
TI  - Disturbed Left Atrial Function is Associated with Paroxysmal Atrial Fibrillation
      in Hypertension.
AB  - BACKGROUND: Hypertension is the most prevalent and modifiable risk factor for
      atrial fibrillation. The pressure overload in the left atrium induces
      pathophysiological changes leading to alterations in contractile function and
      electrical properties. OBJECTIVE: In this study our aim was to assess left atrial
      function in hypertensive patients to determine the association between left
      atrial function with paroxysmal atrial fibrillation (PAF). METHOD: We studied 57
      hypertensive patients (age: 53 +/- 4 years; left ventricular ejection fraction:
      76 +/- 6.7%), including 30 consecutive patients with PAF and 30 age-matched
      control subjects. Left atrial (LA) volumes were measured using the modified
      Simpson's biplane method. Three types of LA volume were determined: maximal
      LA(LAVmax), preatrial contraction LA(LAVpreA) and minimal LA volume(LAVmin). LA
      emptying functions were calculated. LA total emptying volume = LAVmax-LAVmin and
      the LA total EF = (LAVmax-LAVmin )/LAVmax, LA passive emptying volume = LAVmax-
      LAVpreA and the LA passive EF = (LAVmax-LAVpreA)/LAVmax, LA active emptying
      volume = LAVpreA-LAVmin and LA active EF = (LAVpreA-LAVmin )/LAVpreA. RESULTS:
      The hypertensive period is longer in hypertensive group with PAF. LAVmax
      significantly increased in hypertensive group with PAF when compared to
      hypertensive group without PAF (p=0.010). LAAEF was significantly decreased in
      hypertensive group with PAF as compared to hypertensive group without PAF
      (p=0.020). A' was decreased in the hypertensive group with PAF when compared to
      those without PAF (p = 0.044). CONCLUSION: Increased LA volume and impaired LA
      active emptying function was associated with PAF in untreated hypertensive
      patients. Longer hypertensive period is associated with PAF.

PMID- 24676228
TI  - Evaluation of endothelial function on atherosclerosis using perfusion index from
      pulse oximeter.
AB  - BACKGROUND: Endothelial dysfunction is vascular phenomenon that plays an
      important role in atherosclerosis development. With the purpose of improving the
      prevention and treatment of atherosclerotic diseases, the searching for accurate,
      practical and cheaper methods for evaluating endothelial function have become of
      interest. OBJECTIVES: Verify the potential of Peripheral Perfusion Index from
      pulse oximetry (IPP) as a method of endothelial dysfunction evaluation in
      patients with atherosclerotic diseases. METHODS: There were recruited 18 control
      patients and 24 patients with atherosclerotic diseases under optimized treatment,
      in basic health units. The values of IPP were evaluated before and after an
      endothelial-dependent stimulus, the reactive hyperemia. The values of IPP were
      also evaluated in period which the major contribution of Nitric Oxide (NO) for
      the vasodilation occurs (IPP90-120). The results of IPP were discussed using the
      literature and estimating their diagnostic and prognostic potential. RESULTS: The
      endothelium-dependent vasodilatory response measured by IPP was significantly
      lower in patients with atherosclerosis compared to control group, since 45
      seconds after reactive hyperemia. Also, the values of IPP90-120 were
      significantly lower in patients with atherosclerosis [35% (4 - 53%) vs 73% (55 -
      169%); p<0,001]. Similarly, the IPP values were lower in atherosclerosis group
      when it was separated by gender. CONCLUSION: The results of this study, in
      association with the low cost of pulse oximeter, suggest a good potential for IPP
      as an endothelial dysfunction evaluation method. New studies must be done in
      order to clarify this potential and possibly contribute with the prevention and
      treatment of atherosclerotic diseases.

PMID- 24676230
TI  - Neuro-immune modulation of the thymus microenvironment (review).
AB  - The thymus is the primary site for T-cell lympho-poiesis. Its function includes
      the maturation and selection of antigen specific T cells and selective release of
      these cells to the periphery. These highly complex processes require precise
      parenchymal organization and compartmentation where a plethora of signalling
      pathways occur, performing strict control on the maturation and selection
      processes of T lymphocytes. In this review, the main morphological
      characteristics of the thymus microenvironment, with particular emphasis on nerve
      fibers and neuropeptides were assessed, as both are responsible for neuro-immune
      modulation functions. Among several neurotransmitters that affect thymus
      function, we highlight the dopaminergic system as only recently has its
      importance on thymus function and lymphocyte physiology come to light.

PMID- 24676229
TI  - Development of a proficiency testing program for the HIV-1 BED incidence assay in
      China.
AB  - The HIV-1 BED incidence assay was adopted in China in 2005 for HIV-1 incidence
      surveillance. A proficiency testing (PT) program was established in 2006 to
      provide quality assurance services. The BED PT program consisted of two
      components, an international program provided by the U.S. Centers for Disease
      Control and Prevention from 2006 and a domestic program started by the National
      HIV/HCV Reference Laboratory in 2011. Each PT panel consisted of eight coded
      specimens distributed to participating laboratories semi-annually, and testing
      results were collected and analyzed. The number of participating laboratories
      increased progressively from 2006 to 2012. The Chinese HIV-1 incidence laboratory
      network performed satisfactorily both in international and domestic PT programs.
      We also demonstrated that the BED assay was highly reproducible among
      participating laboratories. Our success and lessons learned can be readily
      replicated in other countries or regions contemplating the establishment of a PT
      program for assay-based HIV incidence estimation. 

PMID- 24676232
TI  - Intermolecular proton shuttling in excited state proton transfer reactions:
      insights from theory.
AB  - The mechanism of base to base intermolecular proton shuttling occurring in the
      excited state proton transfer reaction between 7-hydroxy-4
      (trifluoromethyl)coumarin (CouOH) and concentrated 1-methylimidazole base (1
      MeId) in toluene solution is disclosed here by means of a computational approach
      based on Density Functional Theory (DFT) and Time Dependent DFT (TD-DFT). These
      methods allow us to characterize both the ground and excited state potential
      energy surfaces along the proton shuttling coordinate, and to assess the nature
      of the emitting species in the presence of an excess of 1-MeId. As a result, the
      tautomerism of CouOH is found to be photo-activated and, from a mechanistic point
      of view, the calculations clearly show that the overall driving force of the
      entire shuttling is the coumarin photoacidity, which is responsible for both the
      first proton transfer event and the strengthening of the following chain
      mechanism of base to base proton hopping. 

PMID- 24676231
TI  - Defining the geographical range of the Plasmodium knowlesi reservoir.
AB  - BACKGROUND: The simian malaria parasite, Plasmodium knowlesi, can cause severe
      and fatal disease in humans yet it is rarely included in routine public health
      reporting systems for malaria and its geographical range is largely unknown.
      Because malaria caused by P. knowlesi is a truly neglected tropical disease,
      there are substantial obstacles to defining the geographical extent and risk of
      this disease. Information is required on the occurrence of human cases in
      different locations, on which non-human primates host this parasite and on which
      vectors are able to transmit it to humans. We undertook a systematic review and
      ranked the existing evidence, at a subnational spatial scale, to investigate the
      potential geographical range of the parasite reservoir capable of infecting
      humans. METHODOLOGY/PRINCIPAL FINDINGS: After reviewing the published literature
      we identified potential host and vector species and ranked these based on how
      informative they are for the presence of an infectious parasite reservoir, based
      on current evidence. We collated spatial data on parasite occurrence and the
      ranges of the identified host and vector species. The ranked spatial data allowed
      us to assign an evidence score to 475 subnational areas in 19 countries and we
      present the results on a map of the Southeast and South Asia region.
      CONCLUSIONS/SIGNIFICANCE: We have ranked subnational areas within the potential
      disease range according to evidence for presence of a disease risk to humans,
      providing geographical evidence to support decisions on prevention, management
      and prophylaxis. This work also highlights the unknown risk status of large parts
      of the region. Within this unknown category, our map identifies which areas have
      most evidence for the potential to support an infectious reservoir and are
      therefore a priority for further investigation. Furthermore we identify
      geographical areas where further investigation of putative host and vector
      species would be highly informative for the region-wide assessment.

PMID- 24676233
TI  - Axially chiral BODIPYs.
AB  - The synthesis and resolution of a class of chiral organic fluorophores, axially
      chiral 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (Ax*-BODIPY), is described.
      Ax*-BODIPYs were prepared through a modular synthesis combined with a late stage
      Heck functionalisation. Resolution was achieved by preparative chiral HPLC.
      Absolute stereochemical assignment was performed by comparison of experimental
      ECD spectra with TD-DFT calculations. 

PMID- 24676234
TI  - Nanostructured electrochromic films by inkjet printing on large area and flexible
      transparent silver electrodes.
AB  - Printed electrochromic flexible films were obtained by combining transparent
      silver grid electrodes formed by self-assembly and inkjet printed WO3
      nanoparticles. Concentrated dispersions of WO3 nanoparticles were inkjet printed
      on transparent plastic silver grid electrodes with a high transparency of 83% in
      the spectral range of 400-800 nm, and a low sheet resistance in the range of 1-5
      Omega sq(-1). These electrodes were used for electrochromic applications for the
      first time. The resultant patterned nanostructured electrochromic films
      maintained their coloring and bleaching performance after bending of the flexible
      films. 

PMID- 24676235
TI  - In situ synthesis of zeolitic imidazolate frameworks/carbon nanotube composites
      with enhanced CO2 adsorption.
AB  - A series of ZIF-8 and hydroxyl-functionalized carbon nanotube (CNT) composites
      were successfully synthesized by the solvothermal method. The obtained ZIF-8/CNT
      composites were characterized by XRD, SEM, TGA and N2 adsorption at 77 K. The
      contents of ZIF-8 and CNTs in the composites were calculated from thermal
      analysis data. CO2 and N2 adsorption at 273 K on the composites was also
      investigated and compared. The ZIF-8 particles in the composites exhibit similar
      crystal structures and morphology to those of pure ZIF-8, but display enhanced
      thermal stability. The surface areas and pore volumes of the ZIF-8/CNT composites
      are higher than the values calculated for hypothetical physical mixtures, and the
      synergetic effect between ZIF-8 and CNTs can be proposed. This phenomenon
      demonstrates that the incorporation of CNTs into ZIF-8 can facilitate the
      nucleation and crystallization of ZIF-8. As a result, the composites with an
      optimal CNT content (3.63 wt%) show improved CO2 adsorption capacity and higher
      relative selectivity for CO2/N2 compared with pure ZIF-8. 

PMID- 24676236
TI  - [Clinical indications for therapeutic drug monitoring of antifungal agents. In
      the way for optimizing the treatment of fungal infection].
AB  - Therapeutic drug monitoring as a tool in the management of infectious diseases
      has been introduced in therapy with anti-infective agents for years. Nowadays, it
      has taken importance in the management of fungal diseases due to the appearance
      of new antifungal drugs such as new-generation azoles. These azoles have
      pharmacokinetic characteristics that hinder a proper use to ensure efficacy and
      minimize toxicity. Monitoring of serum concentrations may help in the better use
      of these anti-infective agents, as well as in a better management of drug
      interactions, infectious disease and adverse effects. It has resulted in saving
      costs of treatment and in avoiding inadequate dosages. This review will attempt
      to clarify the role of the antifungal agents Therapeutic Drug Monitoring,
      highlighting the role of azole compounds. 

PMID- 24676237
TI  - [Antifungal susceptibility of clinical isolates of Scopulariopsis species].
AB  - INTRODUCTION: Scopulariopsis is a common soil saprophyte. In the last years the
      infections caused by Scopulariopsis species have increased, included superficial
      and invasive mycoses. This fungi has been reported resistant in vitro to some
      antifungal agents, although there is little information about this. The aim of
      the study was to establish in vitro antifungal susceptibility of clinical
      isolates of Scopulariopsis species against to broad-spectrum antifungal agents.
      METHODS: A total of 28 Scopulariopsis strains (10 S. brevicaulis, 7 S. koningii,
      3 S. acremonium, 3 S. candida, 3 S. flava, 1 S. brumptii and 1 S. fusca) were
      tested using Sensititre Yeast One and broth microdilution methods to determine
      the minimum inhibitory concentrations (MICs) to amphotericin B, fluconazole,
      itraconazole, posaconazole, voriconazole and 5-fluorocytosine, and minimun
      effective concentration (MECs) to anidulafungin, caspofungin and micafungin.
      RESULTS: Our data confirm the high in vitro resistance of Scopulariopsis to
      antifungal agents. Anidulafungin, caspofungin, micafungin (MICs >= 8 mg/L), 5
      fluorocytosine (MICs >= 64 mg/L), and fluconazole (MICs >= 128 mg/L) were
      inactive in vitro in all species. MICs of amphotericin B (range 2 to >= 8 mg/L)
      and itraconazole (0.5 to >= 16 mg/L) were high. The best antifungal activity was
      observed for posaconazole and voriconazole (0.5 to >= 8 mg/L). With Sensititre
      Yeast One method MICs obtained slightly lower. Scopulariopsis candida, S. flava
      and S. fusca were the most resistant species, while S. acremonium and S.
      brevicaulis showed the lowest MICs. CONCLUSIONS: MICs of all tested antifungal
      agents for Scopulariopsis were very high. Infections caused by Scopulariopsis
      species may not respond to antifungal treatment. Voriconazole is the drug of
      choice for treatment. We consider it appropriate to add amphotericin B in serious
      infections.

PMID- 24676238
TI  - [Microbiological study of infectious endophthalmitis with positive culture within
      a 13 year-period].
AB  - INTRODUCTION: Our objectives are to describe the microbial spectrum and
      antimicrobial susceptibility of isolates from patients with culture-proven
      endophthalmitis. MATERIAL AND METHODS: Retrospective study of patients with
      microbiological diagnosis of endophthalmitis treated at the Ophthalmology
      Department of the General Hospital La Mancha Centro in the period 1996-2008. The
      identification of isolates was performed using the automated VITEK-2(r) and Api
      galleries (bioMerieux, Spain SA). The antimicrobial susceptibility was performed
      by the VITEK-2(r) system (bioMerieux, Spain SA), E-test strips (MIC Test Strip,
      Liofilchem, Italy) and Sensititre(r) YeastOne trading system (Trek Diagnostic
      Systems, Ohio, USA) for Candida species. RESULTS: Forty four (70%) of 63 cases of
      endophthalmitis were culture positive. Gram-positive bacteria were much more
      common than gram-negative bacteria in both postoperative endophthalmitis (POE)
      and post-traumatic endophthalmitis (PTE). Staphylococcus epidermidis was
      predominant in POE, while Bacillus sp. predominated in the PTE; furthermore, the
      75% of total fungal isolates corresponded to postraumatic cases. The isolated
      strains showed 100% susceptibility to vancomycin, ceftazidime and amikacin, while
      resistance to ciprofloxacin was greater than 15%. The empirical antifungal
      therapy failed in 50% of cases. The visual prognosis was significantly less
      favorable in the PTE. CONCLUSIONS: Based on the susceptibility of our isolates,
      vancomycin, ceftazidime and amikacin are good choices for empirical treatment of
      endophthalmitis, unlike ciprofloxacin. We recommend conducting antifungal
      prophylaxis after penetrating ocular trauma in a rural environment.

PMID- 24676239
TI  - [Antibiotic prescribing and changes in antimicrobial resistances in the health
      area of Segovia (Spain) during the period between 2007 and 2011].
AB  - INTRODUCTION: We analyzed the antibiotic prescribing and resistances of
      respiratory and urinary pathogens more common in the Health Area of Segovia in
      the period 2007-2011. The aim of the study was to investigate variability, time
      trends of antibiotic prescribing and correlation with changes in the
      antimicrobial resistance patterns. MATERIAL AND METHODS: Retrospective cross
      sectional study. Antibiotic consumption was expressed in defined daily doses
      (DDD) per 1000 inhabitants per day (DHD). The antimicrobial resistance was
      expressed in percentages. Trend analysis was performed testing Spearman and
      Pearson correlation coefficients. RESULTS: The average antibiotic prescribing was
      14.17 DHD, the coefficient and low ratio was 38.93% and 17.94. Penicillins was
      the most prescribed group (73%). Rural localization, lack of training MIR,
      distance to hospital and percentage of patients >65 years; showed significant
      association with increased antibiotic prescribing. Resistance of E. coli to
      cotrimoxazole and resistance of H. influenzae to amoxicillin decreased both by
      8%. Resistance of S. pyogenes to erythromycin decreased by 5%. Resistances of S.
      pneumoniae to penicillin and E.coli to cephalosporins were both increased by 12%.
      Correlation between antibiotic prescription and resistances did not show
      singnificative results. CONCLUSIONS: Prescribing of antibiotics decreased by 3.2%
      during the period. The use of broad-spectrum antibiotics was increased.
      Geographic wide variation in antibiotic prescribing was detected, also between
      physicians. There were not obtained conclusive data from the correlation between
      antibiotic prescribing and antimicrobial resistance.

PMID- 24676240
TI  - [Use of Digital Health Records and "WebMovil" corporate service in the
      communication management of critical results of Microbiology, in the context of a
      primary health care area].
AB  - INTRODUCTION: The objective was to describe and evaluate a new communication
      protocol of reporting critical results applied to Microbiology in a health area
      of Andalusia. MATERIAL AND METHODS: The size and type of the critical values of
      Microbiology are analyzed for primary care patients. A new computerized reporting
      system was analyzed, in real time, through Diraya Digital Health Records, which
      integrates the analytical test module (MPA). The protocol is complemented, in
      collaboration with the Information Technology (IT), with the Junta de Andalucia
      short message service (SMS) "WebMovil". RESULTS: The total number of notices of
      critical results by the new protocol in 2012 was 817. The number of critical
      values for primary care was 570, of which 90 were for Microbiology. The most
      frequent notice was by isolation in the stool culture (n = 51; 56.67%). The
      prevalence of the critical values of Microbiology in primary care was 0.45/100.
      The average time of notifications was 13 minutes. The success rate of
      notifications was 97.7% and 0% obtained in the number of withdrawals. In 99.93%
      of cases the contact with the patient was stated and in 98.55% the medical
      intervention was also confirmed. CONCLUSIONS: Communication by a computerized
      system linked to the SMS technology showed a reduction in the time of
      notification, and produced additional benefits, such as eliminating the risk of
      error when there is no repetition of information from the recipient received by
      the laboratory. Furthermore, the use of SMS messages ensures that doctors on duty
      always receive information immediately.

PMID- 24676241
TI  - [Evaluation of galactomannan antigen and Aspergillus real time PCR for diagnosis
      of invasive aspergillosis].
AB  - INTRODUCTION: The aim of the study was to compare the galactomannan antigen (GA)
      and molecular biology (PCRrt) tests with the culture in the diagnosis of invasive
      aspergillosis (IA). MATERIAL AND METHODS: Four hundred and seventy two samples
      were analyzed: 388 respiratory and 84 serum samples from 271 patients. Culture
      and GA were evaluated in the respiratory samples and GA in the serum samples. PCR
      was used when discrepancies were observed among culture and GA tests. RESULTS:
      The detection of GA in serum was positive in 22 (of 84), 21 had the test positive
      respiratory sample. Of the 62 sera with negative GA, 45 were also negative
      respiratory specimens. The culture was positive in 37 of which were positive for
      GA. Comparing culture with AG, it showed PPV=23%, NPV=100%, S=100% and E=52%. The
      PCR showed respect to culture: PPV=69%, NPV=89%, S=64% and E=82%. In sera were
      found in 60% discrepancies between PCRrt and GA. CONCLUSIONS: We consider useful
      the GA detection in serum combined with culture and GA in respiratory samples,
      for diagnosis of AI. PCR requires further studies for standardization and set
      breakpoints.

PMID- 24676242
TI  - Antimicrobial stewardship in patients recently transferred to a ward from the
      ICU.
AB  - PURPOSE: Inappropriate use of antibiotics is an important health problem that is
      related to increasing bacterial resistance. Despite its relevance, many health
      institutions assign very limited resources to improving prescribing practices. An
      antimicrobial stewardship programme (APS) centred on patients discharged from the
      ICU could efficiently undertake this task. METHODS: During this six month study
      the main activity was performing a programmed review of antimicrobial
      prescriptions in patients transferred to the ward from the ICU. In the case of
      inadequate antimicrobial treatment, a recommendation was included in the medical
      record. RESULTS: A total of 437 antimicrobial prescriptions for 286 patients were
      revised during a six month period. In all, 271 prescriptions (62%) were
      considered inappropriate in 183 patients. The most common reasons for
      inappropriateness were treating unconfirmed infection (43%), inadequate
      antimicrobial coverage (34%) and intravenous administration when the oral route
      was feasible (11%). Proposed recommendations were addressed in 212 cases (78%).
      There was no significant difference in adherence with respect to the type of
      recommendation (p=0.417). There was a 5% lower use of antibiotics during the year
      the study was conducted compared to the previous one. CONCLUSIONS: ASPs centred
      on patients discharged from the ICU may be an efficient strategy to ameliorate
      antimicrobial use in hospitals.

PMID- 24676243
TI  - [In vitro emergence of ertapenem resistance in Escherichia coli producing
      extended-spectrum beta-lactamase].
AB  - INTRODUCTION: The occurrence of community-associated infections due to extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli is increasing
      worldwide. These organisms are frequently resistant to many of the antimicrobial
      agents but remain susceptible to carbapenems. We investigated the in vitro
      emergence of carbapenem resistance in a collection of clinical isolates of ESBL 
      producing E. coli. MATERIAL AND METHODS: First and second-step resistant mutants
      were obtained from E. coli with ESBL. Aliquots of 50 MUl containing > 109 CFU
      were applied to Mueller-Hinton plates containing meropenem, imipenem or
      ertapenem. MICs for native strains and mutants were determined using the
      epsilometric test (E-test). RESULTS: Resistant mutants were not selected with
      imipenem or meropenem. E. coli growth was observed on ertapenem (0.5 mg/L)
      containing plates in 13 of 57 clinical isolates (22.8 %).The ertapenem MIC for
      these first-step mutants were >= 1 mg/L, remaining susceptible to imipenem and
      meropenem. The first-step mutants were used as native strains. Six second-step
      resistant mutants were selected with ertapenem. All were fully resistant (CMI >=
      8 mg/L) to ertapenem, three were resistant to meropenem and one to imipenem. Four
      second-step resistant mutants were selected with meropenem. All were resistant to
      ertapenem, meropenem, and two of them were resistant to imipenem. CONCLUSIONS:
      Stable resistant mutants were easy to select with ertapenem among ESBL-producing
      E. coli. Two steps were necessary to select resistant mutants to meropenem or
      imipenem. The use of ertapenem in high-inoculum infections or in undrained focus
      of infection should be monitored to reduce the risk on selection of resistance.

PMID- 24676244
TI  - C. albicans, C. parapsilosis and C. tropicalis invasive infections in the PICU:
      clinical features, prognosis and mortality.
AB  - Candida albicans remains the most common agent associated with invasive Candida
      infection (ICI), but with increasing number of non-albicans species. An
      epidemiological, observational study exploring host criteria, clinical
      characteristics and mortality of ICI was performed in 24 pediatric intensive care
      units (PICU) in Spain. Patients were analyzed in global and distributed by
      infecting species (for groups with >= 15 patients). A total of 125 ICI were
      included: 47 by C. albicans, 37 by C. parapsilosis, 19 by C. tropicalis, 4 C.
      glabrata, and 18 others. Up to 66% of ICI by C. albicans and 75.7% by C.
      parapsilosis occurred in children <= 24 months, while the percentage of children
      >60 months was higher in ICI by C. tropicalis. Bloodstream infection was most
      common among C. tropicalis (78.9%) or C. parapsilosis (83.8%) ICI, but urinary
      infections were almost as common as bloodstream infections among C. albicans ICI
      (31.9% and 38.3%, respectively). Fever refractory to antimicrobials was the most
      frequent host criterion (46.4% patients), but with equal frequency than prolonged
      neutropenia in C. tropicalis ICI. Thrombopenia was more frequent (p<0.05) in C.
      parapsilosis (60.7%) or C. tropicalis (66.7%) ICI than in C. albicans ICI
      (26.5%). Uremia was more frequent (p<0.05) in C. albicans (78.3%) or C.
      tropicalis (73.3%) than in C. parapsilosis ICI (40.7%). Multiple organ failure
      and heart insufficiency was higher in C. tropicalis ICI. Short duration (<= 7
      days) of PICU stay was more frequent in C. albicans ICI. Mortality rates were:
      8.5% (C. albicans ICI), 13.5% (C. parapsilosis ICI) and 23.3% (C. tropicalis
      ICI). ICI by different Candida species showed different clinical profiles and
      mortality, making essential identification at species level.

PMID- 24676245
TI  - [Sternal osteomyelitis and mediastinitis due to Fusobacterium necrophorum].

PMID- 24676246
TI  - [Meningitis caused by Streptococcus salivarius].

PMID- 24676247
TI  - [Suburethral abscess in young woman].

PMID- 24676248
TI  - Guidelines for the management of community-acquired pneumonia in the elderly
      patient.
AB  - The incidence of community-acquired pneumonia (CAP) increases with age and is
      associated with an elevated morbimortality due to the physiological changes
      associated with aging and a greater presence of chronic disease. Taking into
      account the importance of this disease from an epidemiological and prognostic
      point of view, and the enormous heterogeneity described in the clinical
      management of the elderly, we believe a specific consensus document regarding
      this patient profile is necessary. The purpose of the present work was to perform
      a review of the evidence related to the risk factors for the etiology, the
      clinical presentation, the management and the treatment of CAP in elderly
      patients with the aim of elaborating a series of specific recommendations based
      on critical analysis of the literature. This document is the fruit of the
      collaboration of different specialists representing the Spanish Society of
      Emergency Medicine and Emergency Care (SEMES), the Spanish Society of Geriatrics
      and Gerontology (SEGG), the Spanish Society of Chemotherapy (SEQ), the Spanish
      Society of Internal Medicine (SEMI), the Spanish Society of Pneumology and
      Thoracic Surgery (SEPAR) and the Spanish Society of Home Hospitalization (SEHAD).

PMID- 24676250
TI  - Scottish food standards body comes a step closer.

PMID- 24676252
TI  - RCVS Council elections 2014: details and manifestos available online.

PMID- 24676251
TI  - Cattle scab confirmed in Scotland.

PMID- 24676249
TI  - Chemical approaches to therapeutically target the metabolism and signaling of the
      endocannabinoid 2-AG and eicosanoids.
AB  - The endocannabinoid system, most popularly known as the target of the
      psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol (THC), is a
      signaling network that modulates a diverse range of physiological processes
      including nociception, behavior, cognitive function, appetite, metabolism, motor
      control, memory formation, and inflammation. While THC and its derivatives have
      garnered notoriety in the eyes of the public, the endocannabinoid system consists
      of two endogenous signaling lipids, 2-arachidonoylglycerol (2-AG) and N
      arachidonoylethanolamine (anandamide), which activate cannabinoid receptors CB1
      and CB2 in the nervous system and peripheral tissues. This review will focus on
      the recent efforts to chemically manipulate 2-AG signaling through the
      development of inhibitors of the 2-AG-synthesizing enzyme diacylglycerol lipase
      (DAGL) or the 2-AG-degrading enzyme monoacylglycerol lipase (MAGL), and assessing
      the therapeutic potential of DAGL and MAGL inhibitors in pain, inflammation,
      degenerative diseases, tissue injury, and cancer. 

PMID- 24676253
TI  - A world without rinderpest: the FAO looks to the future.

PMID- 24676254
TI  - Website marks the 90th anniversary of the OIE.

PMID- 24676258
TI  - Vet restored to the RCVS Register.

PMID- 24676257
TI  - Collective responsibility key in ensuring equine health and welfare.

PMID- 24676259
TI  - Equine victims of unrest in Egypt.

PMID- 24676260
TI  - Egyptian charity aims to treat and teach.

PMID- 24676261
TI  - Veterinary anaesthesia and analgesia: from chloroform to designer drugs.

PMID- 24676262
TI  - Feline tuberculosis caused by Mycobacterium bovis.

PMID- 24676263
TI  - Unusual cluster of Mycobacterium bovis infection in cats.

PMID- 24676264
TI  - Mycobacterium bovis infection in cats.

PMID- 24676265
TI  - Incursion of RHDV2-like variant in Great Britain.

PMID- 24676266
TI  - History of One Health and One Medicine.

PMID- 24676267
TI  - Cerebellar cortical degeneration in Hungarian vizslas.

PMID- 24676268
TI  - Research on the human-animal bond.

PMID- 24676271
TI  - Cumulative mechanical low-back load at work is a determinant of low-back pain.
AB  - OBJECTIVES: Reported associations of physical exposures during work (eg, lifting,
      trunk flexion or rotation) and low-back pain (LBP) are rather inconsistent.
      Mechanical back loads (eg, moments on the low back) as a result of exposure to
      abovementioned risk factors have been suggested to be important as such loads
      provide a more direct relationship with tissue failure and thus LBP. Since
      information on the effect of such load metrics with LBP is lacking yet, we aimed
      to assess this effect in a prospective study. METHODS: Of 1131 workers,
      categorised into 19 groups, LBP was prospectively assessed over 3 years. Video
      and hand force recordings of 4-5 workers per group (93 in total) were used to
      estimate mechanical low-back loads (peak load and three cumulative load metrics,
      ie, linear weighted load, squared weighted load and load weighted to the tenth
      power) during manual materials handling (MMH) tasks using a video analysis
      method. These data were combined with static mechanical load estimates based on
      structured observation of non-MMH tasks. Associations of mechanical loads and LBP
      were tested using generalised estimating equations. RESULTS: Significant effects
      on LBP were found for cumulative low-back moments (linear and squared weighted;
      both p<0.01 and ORs of 3.01 and 3.50, respectively) but not for peak and
      cumulative moments weighted to the tenth power. CONCLUSIONS: Results of this
      first prospective study on the effect of mechanical low-back load on LBP support
      a LBP aetiology model of cumulative loads, potentially due to accumulation of
      microdamage or fatigue. Therefore, prevention of LBP should focus on reducing
      cumulative low-back loads, especially in highly exposed occupational groups, for
      example, by reducing handling of heavy loads and working in awkward body
      postures.

PMID- 24676270
TI  - Endogenous IL-22 plays a dual role in arthritis: regulation of established
      arthritis via IFN-gamma responses.
AB  - OBJECTIVE: IL-22 is elevated in patients with inflammatory arthritis and
      correlates with disease activity. IL-22 deficient mice have reduced incidence of
      arthritis. Recombinant IL-22 restrains progression of arthritis via increase in
      IL-10 responses when administered prior to onset of arthritis. These findings
      imply a possible dual role of IL-22 in inflammatory arthritis depending on the
      phase of arthritis. Experiments outlined here were designed to elucidate the
      contribution of endogenous IL-22 before and after the onset of arthritis.
      METHODS: Collagen induced arthritis (CIA) was induced in DBA1 or IFN-gamma
      deficient mice following immunization with collagen and complete Freund's
      adjuvant. Anti-IL-22 antibody or isotype control were administered prior to or
      after onset of arthritis and disease progression assessed by clinical scoring and
      histopathology. IL-22, IL-17 and IFN-gamma responses were measured by ELISA and
      flowcytometry. Anti-collagen antibody responses were analyzed by ELISA.
      Expression of IL-22R1 in CD4+ cells was elucidated by flowcytometry and real time
      PCR. RESULTS: Collagen specific IL-22 responses were expanded during arthritis
      and IL-22 producing cells were discrete from IL-17 or IFN-gamma producing cells.
      Neutralization of IL-22 after onset of arthritis resulted in significant increase
      in Th1 responses and significantly reduced severity of arthritis. CD4+ cells from
      arthritic mice showed increased surface expression of IL-22R1. In vitro, CD4+T
      cells cultured with antigen presenting cells in the presence or absence of IL-22
      suppressed or induced IFN-gamma, respectively. The protective effect of anti-IL
      22 was reversed in IFN-gamma deficient mice. Moreover, administration of anti-IL
      22 prior to onset of arthritis augmented arthritis severity. CONCLUSION: We show
      for the first time that IL-22 plays a dual role: protective prior to the onset of
      arthritis and pathogenic after onset of arthritis. The pathogenic effect of IL-22
      is dependent on suppression of IFN-gamma responses. IL-17 responses remained
      unchanged with the administration of anti-IL22 antibody. IL-22R1 is upregulated
      on CD4+T cells during arthritis and regulates IFN-gamma in T cells.

PMID- 24676272
TI  - Differences in the pathogenicity and inflammatory responses induced by avian
      influenza A/H7N9 virus infection in BALB/c and C57BL/6 mouse models.
AB  - Avian influenza A/H7N9 virus infection causes pneumonia in humans with a high
      case fatality rate. However, virus-induced modulation of immune responses is
      being recognized increasingly as a factor in the pathogenesis of this disease. In
      this study, we compared the pathogenicity of A/H7N9 infection in BALB/c and
      C57BL/6 mouse models, and investigated the putative involvement of
      proinflammatory cytokines in lung injury and viral clearance. In both mouse
      strains, A/Anhui/1/2013(H7N9) infection with 10(6) TCID50 resulted in viral
      replication in lung, severe body weight loss and acute lung injury. During the
      early infection stage, infected C57BL/6 mice exhibited more severe lung injury,
      slower recovery from lung damage, less effective viral clearance, higher levels
      of interlukine (IL)-6, monocyte chemotactic protein (MCP)-1, and IL-1beta, and
      lower levels of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma than
      infected BALB/c mice. These results suggest that TNF-alpha and IFN-gamma may help
      suppress viral gene expression and increase viral clearance, and that IL-6 and
      MCP-1 may contribute to lung injury in A/H7N9-infected individuals. In addition,
      lung damage and the distribution of virus antigen in tissues were similar in
      young and middle-aged mice. These results suggest that the more serious lung
      injury in middle-aged or older H7N9 cases is not mainly caused by differences in
      viral replication in the lung but probably by a dysregulated immune response
      induced by underlying comorbidities. These results indicate that the extent of
      dysregulation of the host immune response after H7N9 virus infection most
      probably determines the outcome of H7N9 virus infection.

PMID- 24676273
TI  - Survivors of self-inflicted gunshot wounds to the head: characterization of
      ocular injuries and health care costs.
AB  - IMPORTANCE: Suicides and attempted suicides are major public health issues in the
      United States and around the world. Self-inflicted gunshot wounds (SIGSWs) are a
      common method of attempting suicide, the head being the most commonly injured
      body region; however, the literature lacks an overview of the orbital and ocular
      injuries as well as outcomes associated with SIGSWs. OBJECTIVES: To characterize
      the ocular and orbital injuries and outcomes of patients presenting with SIGSWs
      and to examine the cost associated with these injuries. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective medical record review was performed of all patients
      who presented to the University of Iowa Hospitals and Clinics between 2003 to
      2013 with the admitting diagnosis of self-inflicted injuries via firearms.
      Patients with no periorbital or ocular injuries and/or those who did not survive
      for at least 2 months following the incident were excluded. MAIN OUTCOMES AND
      MEASURES: Ocular injuries and outcomes and health care costs and reimbursements,
      which were generated by a financial report obtained from the hospital finance
      department that included data from both the hospital billing and cost accounting
      systems. RESULTS: All patients in this study (n = 18) were men with a mean age of
      47.2 years. Eight patients (44.4%) displayed submental missile entry points, 7
      (38.9%) displayed intraoral entry points, and 3 (16.7%) displayed pericranial
      entry points. Patients with pericranial entries sustained more severe ocular
      injuries and had poorer ocular outcomes. Seven patients (38.9%) were found at
      final follow-up to have visual acuity of 20/40 or better in each eye and all
      showed missile trajectories in the sagittal plane. The mean cost of treatment of
      these patients totaled $117,338 while the mean reimbursement amount was $124,388.
      CONCLUSIONS AND RELEVANCE: Data regarding ocular injuries and outcomes may assist
      ophthalmologists in the treatment of patients with SIGSWs in the future. Many
      patients had extremely functional vision at final follow-ups, which highlights
      the importance of specialists conducting examinations and reconstructive
      procedures promptly, carefully, and thoroughly. Cost and reimbursement data
      suggest that while these cases place a large financial burden on society, they
      may not burden hospital systems in the same way.

PMID- 24676274
TI  - Improving Diabetes Health Literacy by Animation.
AB  - PURPOSE AND SCOPE: To produce a Spanish/English animated video about diabetes; to
      qualitatively assess cultural and linguistic appropriateness; and to test
      effectiveness at improving diabetes health literacy among Latino/Hispanics.
      METHODS: Participatory research and animation production methods guided
      development of the video. Cultural appropriateness was assessed through focused
      discussion group methods. A prospective randomized controlled trial tested the
      effectiveness of the Spanish version at improving diabetes health literacy,
      compared to "easy to read" diabetes information from the National Institute of
      Diabetes and Digestive and Kidney Diseases. Functional health literacy was
      measured by the Short Test of Functional Health Literacy in Adults. Diabetes
      health literacy was measured by the Diabetes Health Literacy Survey (DHLS).
      RESULTS: No significant differences were recorded between experimental (n = 118)
      and control groups (n = 122) at baseline on demographic characteristics, Short
      Test of Functional Health Literacy in Adults score, or DHLS score. Fifty-eight
      percent of the study participants had inadequate functional health literacy. Mean
      DHLS score for all participants and those having adequate functional health
      literacy were 0.55 and 0.54, respectively (inadequate diabetes health literacy).
      When adjusting for baseline DHLS score, sex, age, and insurance status, DHLS
      scores improved significantly more in the experimental group than the control
      group (adjusted mean = 55% vs 53%, F = 4.7, df = 1, P = .03). Interaction between
      experimental group and health literacy level was significant (F = 6.37, df = 2, P
      = .002), but the experimental effect was significant only for participants with
      inadequate health literacy (P = .009). CONCLUSIONS: The positive effect on DHLS
      scores suggests that animation has great potential for improving diabetes health
      literacy among Latinos having limited functional health literacy. A study is
      needed that targets participants with inadequate health literacy and that uses
      the English and Spanish versions of the video.

PMID- 24676275
TI  - The Relationship of Worry About Hypoglycemia With Diabetes-specific and Typical
      Youth Behavior Among Emerging Adults With Type 1 Diabetes.
AB  - PURPOSE: Little is known about the relationship of worry about hypoglycemia with
      diabetes-specific and typical youth behaviors among emerging adults with type 1
      diabetes. This study's purpose was to examine the relationship among worry about
      hypoglycemia, diabetes management, and glycemic control within the context of
      alcohol use, hypoglycemia-related weight control behaviors, depressive symptoms,
      and impulse control among emerging adults with type 1 diabetes. RESEARCH DESIGN
      AND METHODS: The sample was 181 emerging adults with type 1 diabetes who were
      part of a larger study. Path analysis was used to test associations among worry
      about hypoglycemia, diabetes management, hypoglycemia-related weight control
      behaviors (WCB), alcohol use, impulse control, depressive symptoms, and glycemic
      control. RESULTS: Path model fit and modification indices suggested that a
      feedback loop between worry about hypoglycemia and diabetes management should be
      incorporated into the original model. Youth with fewer depressive symptoms
      reported fewer hypoglycemia-related WCB and less worry about hypoglycemia; those
      with higher impulse control had less alcohol use and better diabetes management;
      those with lower alcohol use had more worry about hypoglycemia; and better
      glycemic control was associated with better diabetes management. CONCLUSIONS:
      Health care professionals need to understand how multiple factors related to
      worry about hypoglycemia and diabetes management interact in emerging adults. In
      the context of depressive symptoms, impulse control, alcohol use, and
      hypoglycemia-related WCB, the path model results suggest several potential
      avenues for intervening to improve glycemic control in emerging adults.

PMID- 24676277
TI  - Undesirable consequences of insecticide resistance following Aedes aegypti
      control activities due to a dengue outbreak.
AB  - BACKGROUND: During a dengue outbreak with co-circulation of DENV-1 and -2 in the
      city of Boa Vista, one patient was diagnosed with DENV-4, a serotype supposed
      absent from Brazil for almost 30 years. The re-emergence of DENV-4 triggered the
      intensification of mechanical and chemical Aedes aegypti control activities in
      order to reduce vector density and avoid DENV-4 dissemination throughout the
      country. METHODS/PRINCIPAL FINDINGS: Vector control activities consisted of (a)
      source reduction, (b) application of diflubenzuron against larvae and (c) vehicle
      mounted space spraying of 2% deltamethrin to eliminate adults. Control activity
      efficacy was monitored by comparing the infestation levels and the number of eggs
      collected in ovitraps before and after interventions, performed in 22 Boa Vista
      districts, covering an area of ~ 80% of the city and encompassing 56,837
      dwellings. A total of 94,325 containers were eliminated or treated with
      diflubenzuron. The most frequently positive containers were small miscellaneous
      receptacles, which corresponded to 59% of all positive breeding sites.
      Insecticide resistance to deltamethrin was assessed before, during and after
      interventions by dose-response bioassays adopting WHO-based protocols. The
      intense use of the pyrethroid increased fourfold the resistance ratio of the
      local Ae. aegypti population only six months after the beginning of vector
      control. Curiously, this trend was also observed in the districts in which no
      deltamethrin was applied by the public health services. On the other hand,
      changes in the resistance ratio to the organophosphate temephos seemed less
      influenced by insecticide in Boa Vista. CONCLUSIONS: Despite the intense effort,
      mosquito infestation levels were only slightly reduced. Besides, the median
      number of eggs in ovitraps remained unaltered after control activity
      intensification. The great and rapid increase in pyrethroid resistance levels of
      natural Ae. aegypti populations is discussed in the context of both public and
      domestic intensification of chemical control due to a dengue outbreak.

PMID- 24676279
TI  - The Swiss NEHAP: why it ended.
AB  - While European countries tend to increase the importance given to their national
      environmental health action plan (NEHAP), Switzerland stopped implementing its
      NEHAP in 2007. This study investigates the reasons for this surprising decision.
      The results provide an explanation of a relatively unique case and should inform
      any person interested in understanding common obstacles in the making and
      implementation of coordinated environmental health policies and programs. Data
      used in this study have been obtained from interviews conducted among experts of
      the Swiss environmental health policies and from survey results provided by the
      WHO Regional Office for Europe. Findings show that financial constraints were
      only partly responsible for the abandonment of the NEHAP and that many of the
      shortcomings observed arose from the creation and the functioning of the
      Environmental and Health Section at the Federal Office of Public Health, which
      was devoted to the NEHAP. Lack of scientific knowledge and capacity to build
      intersectoral collaboration, compounded by a limited conception of environmental
      health, resulted in a lack of political awareness of environmental health issues.
      In consequence, the study highlights the necessity of a true interdisciplinary
      and intersectoral approach for environmental health policies. Policy makers
      should also be concerned with the creation of relevant systems of indicators,
      since they appear to be fundamental to the success of environmental health
      policies. 

PMID- 24676276
TI  - The mechanisms of up-regulation of dendritic cell activity by oxidative stress.
AB  - Whereas DC have increasingly been recognized for their role in activating the
      inflammatory cascades during IRIs, the mechanisms by which oxidative stress
      enhances DC activation remain to be explored. We examined the role of oxidative
      stress on two important features of DC: T cell activation and trafficking. Bone
      marrow-derived OS-DC were compared with untreated DC. DC exposed to oxidative
      stress augmented allogeneic T cell proliferation and showed increased migration
      in a chemotaxis chamber. These results were confirmed by using hypoxanthine and
      xanthine oxidase as another inducer of oxidative stress. We used OT-II and OT-I
      mice to assess the effect of oxidative stress on DC activation of OVA-specific
      CD4(+) and CD8(+) T cells, respectively. Oxidative stress increased DC capacity
      to promote OVA-specific CD4(+) T cell activity, demonstrated by an increase in
      their proliferation and production of IFN-gamma, IL-6, and IL-2 proinflammatory
      cytokines. Whereas oxidative stress increased the DC ability to stimulate IFN
      gamma production by OVA-specific CD8(+) T cells, cellular proliferation and
      cytotoxicity were not affected. Compared with untreated DC, oxidative stress
      significantly reduced the capacity of DC to generate T(regs), which were restored
      by using anti-IL-6. With regard to DC trafficking, whereas oxidative stress
      increased DC expression of p-Akt and p-NF-kappaB, targeting PI3Kgamma and NF
      kappaB pathways abrogated the observed increase in DC migration. Our data propose
      novel insights on the activation of DC by oxidative stress and provide rationales
      for targeted therapies, which can potentially attenuate IRI.

PMID- 24676278
TI  - HIV practitioners in Madrid and New York improving inclusion of underrepresented
      populations in research.
AB  - Practitioners have frequent contact with populations underrepresented in
      scientific research--ethnic/racial groups, sexual minorities and others at risk
      for poor health and whose low participation in research does not reflect their
      representation in the general population. Practitioners aspire to partner with
      researchers to conduct research that benefits underrepresented groups. However,
      practitioners are often overlooked as a work force that can help erase inclusion
      disparities. We recruited (n = 282) practitioners (e.g. physicians, social
      workers, health educators) to examine associations between their attitudes toward
      research purposes, risks, benefits and confidentiality and their involvement in
      recruitment, interviewing and intervention facilitation. Participants worked in
      community-based agencies in Madrid and New York City (NYC), two large and densely
      populated cities. We used cross-sectional data and two-sample tests to compare
      attitudes toward research and practitioner involvement in recruiting,
      interviewing and facilitating interventions. We fit logistic regression models to
      assess associations between practitioner attitudes toward ethical practices and
      recruitment, interviewing and facilitating interventions. The likelihood of
      recruiting, interviewing and facilitating was more pronounced among practitioners
      agreeing more strongly with ethical research practices. Though Madrid
      practitioners reported stronger agreement with ethical research practices, NYC
      practitioners were more involved in recruiting, interviewing and facilitating
      interventions. Practitioners can be trained to improve attitudes toward ethical
      practices and increase inclusion of underrepresented populations in research.
      Funders and researchers are encouraged to offer opportunities for practitioner
      involvement by supporting research infrastructure development in local agencies.
      Practices that promise to facilitate inclusion herein may be used in other
      countries.

PMID- 24676280
TI  - The Fanconi anemia group C protein interacts with uncoordinated 5A and delays
      apoptosis.
AB  - The Fanconi anemia group C protein (FANCC) is one of the several proteins that
      comprise the Fanconi anemia (FA) network involved in genomic surveillance. FANCC
      is mainly cytoplasmic and has many functions, including apoptosis suppression
      through caspase-mediated proteolytic processing. Here, we examined the role of
      FANCC proteolytic fragments by identifying their binding partners. We performed a
      yeast two-hybrid screen with caspase-mediated FANCC cleavage products and
      identified the dependence receptor uncoordinated-5A (UNC5A) protein. Here, we
      show that FANCC physically interacts with UNC5A, a pro-apoptotic dependence
      receptor. FANCC interaction occurs through the UNC5A intracellular domain,
      specifically via its death domain. FANCC modulates cell sensitivity to UNC5A
      mediated apoptosis; we observed reduced UNC5A-mediated apoptosis in the presence
      of FANCC and increased apoptosis in FANCC-depleted cells. Our results show that
      FANCC interferes with UNC5A's functions in apoptosis and suggest that FANCC may
      participate in developmental processes through association with the dependence
      receptor UNC5A. 

PMID- 24676281
TI  - Overweight in adolescence can be predicted at age 6 years: a CART analysis in
      German cohorts.
AB  - OBJECTIVE: To examine, whether overweight in adolescents can be predicted from
      the body mass index (BMI) category, at the age of 6, the mother's education level
      and mother's obesity and to quantify the proportion of overweight at the age of
      14 that can be explained by these predictors. METHOD: Pooled data from three
      German cohorts providing anthropometric and other relevant data to a total of 1
      287 children. We used a classification and regression tree (CART) approach to
      identify the contribution of BMI category at the age of 6 (obese: BMI > 97th
      percentile (P97); overweight: P90 < BMI <= P97; high normal weight: P75<BMI <=
      P90; third quartile: P50<BMI <= P75; below the median: <= P50), maternal
      education level and maternal obesity for prediction of overweight/obesity
      (BMI>P90) at the age of 14. RESULTS: While 4.8% [95%CI: 3.2;7.0] of 651 boys and
      4.1% [95%CI: 2.6;6.2] of 636 girls with a BMI<P75 at age 6 were overweight/obese
      in adolescence, prevalence increased to 41.3% [95%CI: 31.9;51.1] and 42.5%
      [95%CI: 33.8;51.6], respectively, in those with BMI >= P75. The lowest prevalence
      was 1.9% [95%CI: 0.8;3.8] in boys with a BMI <= P50 and the highest prevalence
      91.7% [95%CI: 61.5;99.8] with a BMI>P97 (similar results for girls). BM I >= P75
      at the age of 6 explained 63.5% [95%CI: 51.1;74.5]) and 72.0% [95%CI: 60.4;81.8]
      of overweight/obesity at the age of 14 in boys and girls, respectively.
      CONCLUSIONS: Overweight/obesity in adolescence can be predicted by BMI category
      at the age of 6 allowing for parent counselling or risk guided interventions in
      children with BMI >= P75, who accounted for >2/3 of overweight/obesity in
      adolescents.

PMID- 24676284
TI  - Nicorandil attenuates endothelial VCAM-1 expression via thioredoxin production in
      diabetic rats induced by streptozotocin.
AB  - The anti-angina agent nicorandil has been reported to be beneficial even in
      patients who have angina with diabetes. However, the mechanism underlying the
      effect of nicorandil in patients with diabetes remains to be elucidated. In this
      study, the protective effect of nicorandil on thioredoxin (TRX) protein was
      investigated, as TRX is a multifunctional endogenous redox regulator that
      protects cells against various types of cellular and tissue stress. This study
      was conducted to examine whether nicorandil induces the expression of TRX for the
      protection against diabetic damage in the vascular tissue of rats. Diabetes was
      induced in rats by intraperitoneal injection of streptozotocin (STZ) (fasting
      glucose levels in STZ-induced rats were >14 mmol/l). Diabetic rats were divided
      into a diabetic control and a nicorandil-treated group. Nicorandil was
      administered at a dosage of 15 mg/kg/day by gavage feeding. After five weeks of
      nicorandil administration, blood samples were obtained from the angular vein to
      measure levels of stress markers, serum superoxide dismutase and malondialdehyde,
      using the ELISA. The expression of TRX in STZ-induced rat vascular tissue was
      analyzed by immunohistochemistry, quantitative polymerase chain reaction (qPCR)
      and western blot analysis. The oral administration of nicorandil induced TRX
      protein and mRNA expression in the vascular tissue of STZ-induced diabetic rats.
      In the diabetic control group, the levels of stress were markedly higher than
      those in the nicorandil-treated group, indicating that nicorandil reduces
      oxidative stress in serum. In addition to inducing TRX expression, nicorandil
      attenuated the expression of the vascular cell adhesion molecule-1 (VCAM-1) in
      diabetic rat vascular endothelial cells. In conclusion, nicorandil attenuates the
      formation of reactive oxygen species and induces TRX protein expression,
      consequently resulting in the suppression of VCAM-1 secretion in the vascular
      endothelial cells of STZ-induced diabetic rats.

PMID- 24676285
TI  - Laboratory spectroscopy of astrophysically relevant carbon species.
AB  - Carbon is one of the most common elements in the solar system, with a fractional
      abundance of 10(-4) relative to hydrogen. Thus, it is not surprising that over
      100 carbon-bearing species have been definitively detected in the interstellar
      medium via their rotational, infrared, and/or electronic transitions. In order to
      identify these species, laboratory spectra are needed for comparison to
      astronomical data. Challenges arise when obtaining laboratory spectra due to the
      instability of many of these molecules. Over the years, sensitive instrumentation
      and better techniques for producing these species in situ have been developed to
      achieve this goal. The use of complementary spectroscopic methods, such as matrix
      isolation, cavity ringdown, resonance enhanced multiphoton ionization, and ion
      trapping have led to the identification of several new carbon species at optical
      and ultraviolet wavelengths. Laboratory spectra have been compared to
      astronomical data in order to gain further insight into interstellar chemistry.
      In particular, attempts have been made to identify the carriers of the diffuse
      interstellar bands, however, with little success. These results are discussed in
      the following review. 

PMID- 24676282
TI  - Quality of care after acute coronary syndromes in a prospective cohort with
      reasons for non-prescription of recommended medications.
AB  - BACKGROUND: Adherence to guidelines is associated with improved outcomes of
      patients with acute coronary syndrome (ACS). Clinical registries developed to
      assess quality of care at discharge often do not collect the reasons for non
      prescription for proven efficacious preventive medication in Continental Europe.
      In a prospective cohort of patients hospitalized for an ACS, we aimed at
      measuring the rate of recommended treatment at discharge, using pre-specified
      quality indicators recommended in cardiologic guidelines and including systematic
      collection of reasons for non-prescription for preventive medications. METHODS:
      In a prospective cohort with 1260 patients hospitalized for ACS, we measured the
      rate of recommended treatment at discharge in 4 academic centers in Switzerland.
      Performance measures for medication at discharge were pre-specified according to
      guidelines, systematically collected for all patients and included in a
      centralized database. RESULTS: Six hundred and eighty eight patients(54.6%) were
      discharged with a main diagnosis of STEMI, 491(39%) of NSTEMI and 81(6.4%) of
      unstable angina. Mean age was 64 years and 21.3% were women. 94.6% were
      prescribed angiotensin converting enzyme inhibitors/angiotensin II receptor
      blockers at discharge when only considering raw prescription rates, but increased
      to 99.5% when including reasons non-prescription. For statins, rates increased
      from 98% to 98.6% when including reasons for non-prescription and for beta
      blockers, from 82% to 93%. For aspirin, rates further increased from 99.4% to
      100% and from to 99.8% to 100% for P2Y12 inhibitors. CONCLUSIONS: We found a very
      high adherence to ACS guidelines for drug prescriptions at discharge when
      including reasons for non-prescription to drug therapy. For beta-blockers,
      prescription rates were suboptimal, even after taking into account reason for non
      prescription. In an era of improving quality of care to achieve 100% prescription
      rates at discharge unless contra-indicated, pre-specification of reasons for non
      prescription for cardiovascular preventive medication permits to identify
      remaining gaps in quality of care at discharge. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01000701.

PMID- 24676286
TI  - A two-ring interlocked DNA catenane rotor undergoing switchable transitions
      across three states.
AB  - A two-ring (alpha/beta) interlocked DNA catenane rotor system is described. Using
      appropriate fuel and anti-fuel strands, the triggered switchable rotation across
      three states S1, S2 and S3 associated with the circular track of ring alpha is
      demonstrated. 

PMID- 24676288
TI  - Heller's myotomy: a hundred years of success!

PMID- 24676287
TI  - Involvement of the SATB1/F-actin complex in chromatin reorganization during
      active cell death.
AB  - Over the past years, confirmations on the presence of actin and/or its
      polymerized form, F-actin, in the cell nucleus are progressively accumulating.
      Nevertheless, the function and localization of F-actin in the nucleus is still
      not fully characterized. Thus, the aim of the present study was to evaluate the
      association between F-actin and sequence-binding protein 1 (SATB1) and their
      involvement in chromatin remodeling associated with active cell death. Both SATB1
      and F-actin were colocalized in the transcriptional active regions of the cell
      nucleus and a functional interaction was observed between SATB1 and higher
      organized nuclear F-actin structures at the border between condensed and
      decondensed chromatin. These results extend the knowledge on the role of SATB1
      and nuclear F-actin in three-dimensional chromatin organization and their
      functions during active cell death. Additionally, this study opens the discussion
      on the involvement of the SATB1/F-actin functional complex in active cell death;
      further studies are required to fully elucidate these issues.

PMID- 24676289
TI  - Influence of exercise testing in gastroesophageal reflux in patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND: Gastroesophageal reflux disease is a worldwide prevalent condition
      that exhibits a large variety of signs and symptoms of esophageal or extra
      esophageal nature and can be related to the esophagic adenocarcinoma. In the last
      few years, greater importance has been given to the influence of physical
      exercises on it. Some recent investigations, though showing conflicting results,
      point to an exacerbation of gastroesophageal reflux during physical exercises.
      AIM: To evaluate the influence of physical activities in patients presenting with
      erosive and non erosive disease by ergometric stress testing and influence of the
      lower esophageal sphincter tonus and body mass index during this situation.
      METHODS: Twenty-nine patients with erosive disease (group I) and 10 patients with
      non-erosive disease (group II) were prospectively evaluated. All the patients
      were submitted to clinical evaluation, followed by upper digestive endoscopy,
      manometry and 24 h esophageal pH monitoring. An ergometric testing was performed
      1 h before removing the esophageal pH probe. During the ergometric stress
      testing, the following variables were analyzed: test efficacy, maximum oxygen
      uptake, acid reflux duration, gastroesophageal reflux symptoms, influence of the
      lower esophageal sphincter tonus and influence of body mass index in the
      occurrence of gastroesophageal reflux during these physical stress. RESULTS:
      Maximum oxigen consumption or VO 2 max, showed significant correlation when it
      was 70% or higher only in the erosive disease group, evaluating the patients with
      or without acid reflux during the ergometric testing (p=0,032). The other
      considered variables didn't show significant correlations between
      gastroesophageal reflux and physical activity (p>0,05). CONCLUSIONS: 1) Highly
      intensive physical activity can predispose the occurrence of gastroesophageal
      reflux episodes in gastroesophageal reflux disease patients with erosive disease;
      2) light or short sessions of physical activity have no influence on reflux,
      regardless of body mass index; 3) the lower esophageal sphincter tonus does not
      influence the occurrence of reflux disease episodes during exercise testing.

PMID- 24676290
TI  - Double-blind prospective randomized study comparing polyethylene glycol to
      lactulose for bowel preparation in colonoscopy.
AB  - BACKGROUND: Colonoscopy is the most frequent exam used to evaluate colonic
      mucosa, allowing the diagnosis and treatment of many diseases. The appropriate
      bowel preparation is indispensable for the realization of colonoscopy. Therefore,
      it is necessary the use of laxative medications, preferentially by oral
      administration. AIM: To compare two medications used in bowel preparation in
      adult patients going to ambulatory colonoscopy and to analyze the patients'
      profile. METHODS: A double-blind prospective study with 200 patients, randomized
      in two groups: one that received polyethilene glycol and another that received
      lactulose. The patients answered to questionnaires to data compilation, as
      tolerance, symptoms and complications related to preparation. Besides, it was
      also evaluated the prepare efficacy related to the presence of fecal residue.
      RESULTS: Intestinal habit alterations and abdominal pain were the main reasons to
      realize the exams and hypertension was the most prevalent comorbidity. Ten
      percent of the ones who received lactulose didn't get to finish the preparation
      and 50% considered the taste "bad, but tolerable". The most common subjective
      symptom after the medication was nausea, especially after lactulose. During the
      exam, most of the patients who used lactulose had a "light discomfort" and the
      ones who used polyethilene glycol considered the discomfort as "tolerable". The
      quality of the preparation was good in 75%, undependable of the medication that
      was used. CONCLUSION: Polyethilene glycol was more tolerable when compared to
      lactulose, without difference on the quality of the preparation.

PMID- 24676291
TI  - Adductor pollicis muscle as predictor of malnutrition in surgical patients.
AB  - BACKGROUND: In the compromised nutritional status, there is excessive skeletal
      muscle loss and decreased inflammatory response, contributing to increased
      morbidity and mortality and length of stay. AIM: To estimate the prevalence of
      malnutrition by measuring adductor pollicis muscle using cutoffs for surgical
      patients suggested in the literature. METHODS: Cross-sectional study with 151
      patients scheduled for elective surgical procedure. Nutritional assessment was
      performed by classical anthropometric measurements: arm circumference, triceps
      skinfold thickness, arm muscle circumference, corrected arm muscle area, BMI and
      percentage of weight loss and the extent of the adductor pollicis muscle in both
      hands. RESULTS: The prevalence of malnutrition in patients was high. A
      significant association between nutritional diagnosis according to the measures
      of adductor pollicis muscle and arm circumference, BMI and triceps skinfold
      thickness but there was no association with arm muscular circumference, arm
      muscular area or percentage of weight loss. CONCLUSION: The adductor pollicis
      muscle has proved to be a good method to diagnose muscle depletion and
      malnutrition in surgical patients.

PMID- 24676292
TI  - The presence of metastases in regional lymph nodes is associated with tumor size
      and depth of invasion in sporadic gastric adenocarcinoma.
AB  - BACKGROUND: Gastric adenocarcinoma is more often found in men over 50 years in
      the form of an antral lesion. The tumor has heterogeneous histopathologic
      features and a poor prognosis (median survival of 15% in five years). AIM: To
      estimate the relationship between the presence of nodal metastasis and other
      prognostic factors in sporadic gastric adenocarcinoma. METHOD: Were evaluated 164
      consecutive cases of gastric adenocarcinoma previously undergone gastrectomy
      (partial or total), without clinical evidence of distant metastasis, and
      determined the following variables: topography of the lesion, tumor size,
      Borrmann macroscopic configuration, histological grade, early or advanced
      lesions, Lauren histological subtype, presence of signet ring cell, degree of
      invasion, perigastric lymph node status, angiolymphatic/perineural invasion, and
      staging. RESULTS: Were found 21 early lesions (12.8%) and 143 advanced lesions
      (87.2%), with a predominance of lesions classified as T3 (n=99/60, 4%) and N1
      (n=62/37, 8%). The nodal status was associated with depth of invasion (p<0.001)
      and tumor size (p<0.001). The staging was related to age (p=0.048), histological
      grade (p=0.003), and presence of signet ring cells (p = 0.007), angiolymphatic
      invasion (p = 0.001), and perineural invasion (p=0.003). CONCLUSION: In gastric
      cancer, lymph node involvement, tumor size and depth of invasion are
      histopathological data associated with the pattern of growth/tumor spread,
      suggesting that a wide dissection of perigastric lymph nodes is a fundamental
      step in the surgical treatment of these patients.

PMID- 24676293
TI  - Suprapubic laparoscopic cholecystectomy: technique and preliminary results.
AB  - BACKGROUND: The minimally invasive abdominal surgery has evolved to reduce
      portals, culminating with a single incision and natural orifice operation.
      However, these methods are still expensive, difficult to implement and with
      questionable aesthetic results. AIM: To present the standardization and
      preliminary results of a technique for performing laparoscopic suprapubic access
      by the principle which was called the Supra Pubic Endoscopic Surgery for
      cholecystectomy. METHOD: The average body mass index of patients, the mean
      operative time, clinical data of the postoperative complications and quality of
      life were prospectively studied. The operation incisions consisted of: A)
      umbilical for instrumental dissection and clipping; B) in the right groin for
      handling and gallbladder gripping; C) suprapubic for the camera. With the patient
      in reverse Trendelenburg and left lateral decubitus, the operation flew by the
      camera trocar in C, proceeding with dissection and isolation of the biliary
      pedicle, identification of cystic duct and artery, with usual instrumentation.
      Transcystic intraoperative cholangiography was performed in all cases in which
      there were indications. The procedure was completed with clipping and sectioning
      of the cystic duct and artery, retrograde resection of the gallbladder and
      extracting it by the umbilical trocar incision under direct vision. RESULTS:
      Thirty patients undergone this surgical procedure between March and June 2012 and
      were evaluated. The mean age was 40.7 years and the indications were typical
      biliary colic in 18 cases (60 %), cholecystitis in five cases (16.6 %), biliary
      pancreatitis in one case (3.3%); polyp in three cases (10%) and obstructive
      jaundice at three cases (10%). The average body mass index was 27.8 (23.1-35.1)
      and surgical time ranged between 24 and 70 minutes. CONCLUSION: The technique
      proved to be feasible and safe , with no significant complications, and
      satisfactory cosmetic results.

PMID- 24676294
TI  - Use of alloplastic meshes in abdominal wounds of rats with induced peritonitis.
AB  - BACKGROUND: The use of alloplastic meshes has been historically contra-indicated
      in patients with infection. AIM: To evaluate the use of polypropylene meshes in
      the treatment of abdominal wall defects in rats with peritonitis. METHODS: Twenty
      Wistar female rats were divided into two groups: induction of peritonitis (test
      group) and without peritonitis (control group). An abdominal wall defect was
      created in all animals, and polypropylene mesh was applied. The evaluation of the
      tensile strength of the mesh was carried out using tensiometer and microscopic
      analysis of the healing area was done. RESULTS: More adhesion of the mesh to the
      rat abdominal wall was observed in test group. The histopathological analyses
      showed prevalence of moderate to accentuated granulation tissue in both groups,
      without significant differences. CONCLUSION: The use of the mesh coverage on
      abdominal wall defects of rats with induced peritonitis did not show worse
      results than its use in healthy animals, nor was its integration to the resident
      tissue any worse.

PMID- 24676295
TI  - Quality of life of in patients submitted to anterior abdominal wall laparoscopic
      hernioplasty.
AB  - BACKGROUND: The laparoscopic ventral hernia repair technique made possible
      surgeries with smaller skin incisions and smaller dissection of the soft tissue
      around the hernia, therefore with a better wound, a quicker postoperative
      recovery and a lower complication rate. AIM: To evaluate the applicability of a
      quality of life survey based on the molds of the American Hernia Society,
      European Hernia Society and Carolinas Equation for Quality of Life, through
      telephone in patients submitted to laparoscopic hernioplasty by IPOM technique.
      METHODS: A retrospective cohort study was made to evaluate the quality of life of
      21 patients that underwent anterior abdominal wall laparoscopic hernioplasty by
      intraperitoneal onlay mesh technique. Questionnaire was applied through
      telephone. RESULTS: Of the 21 patients, 19% felt that the hernia recurred. Also
      19% passed through another abdominal wall surgery, and among these, 75% was
      related to the previously hernia correction. Finally, 81% of patients did not
      undergo any other abdominal wall surgery. CONCLUSION: It was possible to apply
      the quality of life questionnary by telephone on patients who underwent an
      anterior abdominal wall. The results, in its turn, were satisfactory and showed
      that patients, in general, were satisfied with the surgical procedure.

PMID- 24676296
TI  - Single-incision videolaparoscopic appendectomy with conventional videolaparoscopy
      equipment.
AB  - BACKGROUND: Acute appendicitis is the most common surgical emergency in daily
      practice, and is approached laparoscopically in many centers. Efforts have been
      undertaken for the development of minimally invasive techniques that reduce
      tissue trauma and offer improved cosmetic results, one of such being the single
      incision laparoscopic surgery (SILS). AIM: To present a minimally invasive
      technique for appendectomy (SILS) undertaken with conventional instruments.
      METHOD: Eleven patients were treated in the emergency care center presenting
      abdominal pain in the right iliac fossa that was suggestive of appendicitis.
      Diagnostic investigation was subsequently conducted, including physical
      examination, laboratory and imaging exams (CT scan with intravenous contrast or
      total abdominal ultrasound), and the results were consistent with acute
      appendicitis. Thus, after consent, these patients underwent SILS appendectomy
      under general anesthesia with three trocars (two 10 mm and one 5 mm), using
      conventional and optical laparoscopic tweezers (10 mm, 30o). The base and pedicle
      of the appendix were ligated with titanium LT 400 clips. The procedure occurred
      uneventfully. Inclusion criteria were absence of diffuse peritonitis, BMI (body
      mass index) less than 35 and absence of serious comorbidities or sepsis. RESULTS:
      Seven men and four women were operated with average age of 25.7 years and
      underwent appendectomy through this technique. Mean procedure duration was of
      37.2 min. Regarding surgical findings, three had appendicitis in stage 1, four in
      stage 2 and four in stage 3. All patients improved well, without surgical
      complications, and did not require conversion to open surgery or conventional
      laparoscopy technique. CONCLUSION: Appendectomy conducted through Single Incision
      Laparoscopic Surgery is a feasible and promising technique that can be performed
      with conventional laparoscopic instruments.

PMID- 24676297
TI  - Bariatric surgery reverses metabolic risk in patients treated in outpatient
      level.
AB  - BACKGROUND: The conventional treatment of obesity presents unsatisfactory results
      on weight loss and its long-term sustainability, therefore bariatric surgery has
      been suggested as an effective therapy, determining sustainable long-term weight
      loss, reversal of components of cardiometabolic risk and improved quality and
      life expectancy. AIM: To investigate the clinical component of the
      cardiometabolic risk in patients undergoing bariatric surgery assisted on
      outpatient basis. Methods : The sample consisted of 47 patients with ages between
      18 and 60 years, 72% females. Diabetes mellitus, hypertension, and dyslipidemia
      were prospectively evaluated by using the Assessment of Obesity-Related Co
      morbidities scale. RESULTS: Occurred improvement in these co-morbidities within
      12 months after surgery. Co-morbidities resolved were greater than those
      improved. CONCLUSION: The study revealed that the Assessment of Obesity-Related
      Co-morbidities is a system that can be effectively used to quantify the degree of
      reduction of the severity of the cardiometabolic risk in response to bariatric
      surgery.

PMID- 24676298
TI  - Fundamental frequency, phonation maximum time and vocal complaints in morbidly
      obese women.
AB  - BACKGROUND: Obese people have abnormal deposition of fat in the vocal tract that
      can interfere with the acoustic voice. Aim : To relate the fundamental frequency,
      the maximum phonation time and voice complaints from a group of morbidly obese
      women. METHODS: Observational, cross-sectional and descriptive study that
      included 44 morbidly obese women, mean age of 42.45 (+/- 10.31) years old,
      observational group and 30 women without obesity, control group, with 33.79 (+/-
      4.51)years old. The voice recording was done in a quiet environment, on a laptop
      using the program ANAGRAF acoustic analysis of speech sounds. To extract the
      values of fundamental frequency the subjects were asked to produce vowel [a] at
      usual intensity for a period in average of three seconds. After the voice
      recording, participants were prompted to produce sustained vowel [ a] , [ i] and
      [ u] at usual intensity and height, using a stopwatch to measure the time that
      each participant could hold each vowel. RESULTS: The majority, 31(70.5%), had
      vocal complaints, with a higher percentage for complaints of vocal fatigue
      20(64.51%) and voice failures 19(61.29%) followed by dryness of the throat in 15
      (48.38%) and effort to speak 13(41.93%). There was no statistically significant
      difference regarding the mean fundamental frequency of the voice in both groups,
      but there was significance between the two groups regarding maximum phonation.
      CONCLUSION: Increased adipose tissue in the vocal tract interfered in the vocal
      parameters.

PMID- 24676299
TI  - Hepatectomy: a critical analysis on expansion of the indications.
AB  - BACKGROUND: Hepatic resection has evolved to become safer, thereby making it
      possible to expand the indications. Aim : To assess the results from a group of
      patients presenting these expanded indications. METHOD: Were prospectively
      studied all the hepatectomy procedures performed for hepatic tumor resection.
      Patients with benign and malignant primary and secondary tumors were included.
      Were included variables such as age, gender, preoperative diagnosis, preoperative
      treatment, type of operation performed, need for transfusion, final
      anatomopathological examination and postoperative evolution. The patients were
      divided into two groups: group A, with a traditional indication for hepatectomy;
      and group B, with an expanded indication (tumors in both hepatic lobes, extensive
      resection encompassing five or more segments, cirrhotic livers and postoperative
      chemotherapy using hepatotoxic drugs). RESULTS: Were operated 38 patients, and 40
      hepatectomies were performed: 28 patients in group A and 10 in group B. The mean
      age was 57.7 years, and 25 patients were women. Three in group B were operated as
      two separate procedures. Groups A and B received means of 1.46 and 5.5 packed red
      blood cell units per operation, respectively. There were three cases with
      complications in group A (10.7%) and six in group B (60%). The mortality rate in
      group A was 3.5% (one patient) and in groups B, 40% (four patients). The imaging
      examinations were sensitive for the presence of tumors but not for defining the
      type of tumor. The blood and derivative transfusion rates, morbidity and
      mortality were greater in the group with expanded indications and more extensive
      surgery. CONCLUSION: The indications for liver biopsy and portal vein
      embolization or ligature can be expanded, with special need of cooperation of the
      anesthesiology department and the use of hepatic resection devices to diminish
      blood transfusion.

PMID- 24676300
TI  - Combined liver-kidney transplantation: experience at a Brazilian university
      hospital.
AB  - BACKGROUND: Combined liver-kidney transplant is a routine procedure in many
      transplant centers. The increase in its number coincided with the introduction in
      2002 of the MELD (Model for End-stage Liver Disease) score for allocation of
      livers, prioritizing patients with renal dysfunction. Aim : To analyze the
      experience with combined liver-kidney transplantation in a liver transplant
      center in Brazil. METHOD: A retrospective review was conducted. All transplants
      were performed using grafts from deceased donors. RESULTS: Sixteen combined liver
      kidney transplantations were performed in the same period, which corresponds to
      2.7% and 2.5% of the kidney and liver transplants, respectively. Fourteen
      patients were male (87.5 %) and two were female (12.5%). The average patients and
      donors age was 57.3 +/- 9.1 and 32.7 +/- 13.1, respectively. The MELD score mean
      was 23.6 +/- 3.67. The main cause of liver dysfunction were chronic hepatitis C
      virus (n=9). As for renal dysfunction, diabetic nephropathy (n=4) was the most
      frequent. There were six deaths, two of them by severe dysfunction of the liver
      graft and four by infectious causes. The 1, 3 and 5 years survival rate in
      patients undergoing liver-kidney transplantations was 68.8%, 57.3% and 57.3%,
      respectively. CONCLUSION: The survival rates achieved in this series are
      considered satisfactory and show that this procedure has an acceptable morbidity
      and survival.

PMID- 24676301
TI  - Hypoxia among patients on the liver-transplant waiting list.
AB  - BACKGROUND: Hepatopulmonary syndrome is formed by a triad of liver disease,
      intrapulmonary vascular dilatation and changes in blood gases. This condition is
      present in 4-32% of patients with cirrhosis. AIM: To analyze the blood gas
      changes data of patients in liver-transplant waiting list. METHOD: Clinical data
      of 279 patients in liver transplantation waiting list in May 2013 were studied.
      Overall patient was analyzed by the demographic aspects, laboratorial and image
      findings on exams that determine lung disease (hypoxemia) in these cirrhotic
      patients. The mean values and standard deviations were used to examine normally
      distributed variables. RESULTS: There was a high prevalence of male patients
      (68%); the mean age was 51(+/- 5,89) years, and the predominant reason for
      listing was hepatitis C cirrhosis. The MELD score mean was 16 +/- 5,89, without
      prioritization or special situation. The most common blood type was O in 129
      cases (46%) and the mean of body max index was 25,94 +/- 4,58. Regarding arterial
      blood gas tests was observed 214 patients with PaO2 <90 mmHg, 80 with PaO2 <80
      mmHg and 39 with PaO2 <50 mmHg. In relation to O2 saturation, 50 patients had
      <90%, 33 <80% and 10 <50%. CONCLUSION: Was observed a high rate of hypoxemia in
      patients on waiting list liver transplant. Due to the high severity and
      morbidity, is suggested better monitoring and therapeutic support to hypoxemic
      patients on liver transplant waiting list.

PMID- 24676302
TI  - High definition endoscopy and "narrow band imaging" in the diagnosis of
      gastroesophageal reflux disease.
AB  - INTRODUCTION: The gastroesophageal reflux disease is a common condition in the
      western world but less than half of patients present endoscopic abnormalities,
      making a standard procedure unsuitable for diagnosis. High definition endoscopy
      coupled with narrow band imaging has shown potential for differentiation of
      lesions and possible biopsy, allowing early diagnosis and treatment. METHODS:
      This review describes the principles of biotic and their influence in obtaining
      images with better definition of the vessels in the mucosa, through the narrow
      band imaging. Selected papers using it in patients with reflux disease and
      Barrett's esophagus are analyzed in several ways, highlighting the findings and
      limitations. CONCLUSION: The meaning of the narrow band imaging in the endoscopic
      diagnosis of reflux disease will be defined by large scale studies, with
      different categories of patients, including assessment of symptoms and response
      to treatment.

PMID- 24676303
TI  - Surgical treatment of hemorrhoids: a critical appraisal of the current options.
AB  - INTRODUCTION: Surgical treatment of hemorrhoids is still a dilemma. New
      techniques have been developed leading to a lower rate of postoperative pain;
      however, they are associated with a greater likelihood of recurrence. AIM: To
      review current indications as well as the results and complications of the main
      techniques currently used in the surgical treatment of hemorrhoidal disease.
      METHODS: A systematic search of the published data on the options for treatment
      of hemorrhoids up to December 2012 was conducted using Medline/PubMed, Cochrane,
      and UpToDate. RESULTS: Currently available surgical treatment options include
      procedure for prolapse and hemorrhoids (PPH), transanal hemorrhoidal
      dearterialization (THD), and conventional hemorrhoidectomy techniques. Excisional
      techniques showed similar results regarding pain, time to return to normal
      activities, and complication rates. PPH and THD were associated with less
      postoperative pain and lower complication rates; however, both had higher
      postoperative recurrence rates. CONCLUSION: Conventional surgical techniques
      yield better long-term results. Despite good results in the immediate
      postoperative period, PPH and THD have not shown consistent long-term favorable
      results.

PMID- 24676304
TI  - Step-by-step esophagojejunal anastomosis after intra-corporeal total gastrectomy
      for laparoscopic gastric cancer treatment: technique of "reverse anvil".
AB  - BACKGROUND: The laparoscopic gastrectomy is a relatively new procedure due mainly
      to the difficulties related to lymphadenectomy and reconstruction. Until the
      moment, technique or device to perform the esophagojejunal anastomosis by
      laparoscopy is still a challenge. So, a safe, cheap and quickly performing
      technique is desirable to be developed. AIM: To present technique proposed by the
      authors with its technical details on reconstruction with "reverse anvil".
      METHOD: After total gastrectomy completed intra-corporeally, the reconstruction
      starts with the preparation of the intra-abdominal esophagus cross-section next
      to the esophagogastric transition of 50%. A graduated device is prepared using
      Levine gastric tubes (no. 14 and 10), 3 cm length, connected to the anvil of the
      circular stapler (no. 25) with a wire thread (2-0 or 3-0) of 10 cm, which is
      connected to end of this device. The whole device is introduced in reverse
      esophagus. The esophagus is amputated and the wire is pulled after previous
      transfixation in the distal esophagus and the anvil positioned. The jejunal loop
      is sectioned 20-30 cm from duodenojejunal angle, and the anvil put in the jejunal
      loop and connect previously in the esophagus. Linear stapler (blue 60 mm) is used
      to close the opening of the jejunal loop. CONCLUSION: The "reverse anvil"
      technique used by the authors facilitated the transit reestablishment after total
      gastrectomy, contributing to obviate reconstruction problems after total
      gastrectomy.

PMID- 24676305
TI  - Video-assisted anal fistula treatment: technical considerations and preliminary
      results of the first Brazilian experience.
AB  - BACKGROUND: Anorectal fistula represents an epithelized communication path of
      infectious origin between the rectum or anal canal and the perianal region. The
      association of endoscopic surgery with the minimally invasive approach led to the
      development of the video-assisted anal fistula treatment. AIM: To describe the
      technique and initial experience with the technique video-assisted for anal
      fistula treatment. TECHNIQUE: A Karl Storz video equipment was used. Main steps
      included the visualization of the fistula tract using the fistuloscope, the
      correct localization of the internal fistula opening under direct vision,
      endoscopic treatment of the fistula and closure of the internal opening which can
      be accomplished through firing a stapler, cutaneous-mucosal flap, or direct
      closure using suture. RESULTS: The mean distance between the anal verge and the
      external anal orifice was 5.5 cm. Mean operative time was 31.75 min. In all
      cases, the internal fistula opening could be identified after complete
      fistuloscopy. In all cases, internal fistula opening was closed using full
      thickness suture. There were no intraoperative or postoperative complications.
      After a 5-month follow-up, recurrence was observed in one (12.5%) patient.
      CONCLUSION: Video-assisted anal fistula treatment is feasible, reproducible, and
      safe. It enables direct visualization of the fistula tract, internal opening and
      secondary paths.

PMID- 24676306
TI  - An unusual small bowel obstruction (abdominal cocoon): a case report.

PMID- 24676307
TI  - Spontaneous rectus sheath hematoma associated with low dose of acetylsalicylic
      acid.

PMID- 24676308
TI  - Closure of large wound with rubber elastic circular strips - case report.

PMID- 24676309
TI  - Emergency right hepatectomy for porta hepatis injury during laparoscopic
      cholecystectomy.

PMID- 24676310
TI  - Photocatalytic hydrogen production from water under visible light irradiation
      using a dye-sensitized attapulgite nanocrystal photocatalyst.
AB  - Attapulgite (ATP), not only as a type of natural and low cost silicate clay
      mineral but also as a high quality nanosized material with large surface area,
      layered and lath-like structure, has been found to have a wide variety of
      industrial applications. The ideal composition of ATP is Mg5Si8O20(OH)2(OH2)4.
      However, according to previous reports from different countries in the world, it
      is very important for our research that the actual composition of ATP varies
      because of partial replacement of magnesium by aluminum, iron, titanium and other
      elements. Herein, we have successfully used this dye sensitized clay mineral (raw
      and purified) to effectively reduce water for hydrogen generation under visible
      light irradiation. Further chemical analysis as well as computational simulation
      (CS) proposed that the natural Fe-doping (two ATP crystal cells sharing one Fe
      atom) can promote the photocatalytic process. 

PMID- 24676311
TI  - A novel type of coordination mode of chloranilic acid leading to the formation of
      polymeric coordination ribbon in the series of mixed-ligand copper(II) complexes
      with 1,10-phenanthroline.
AB  - A series of four novel mixed-ligand complexes of copper(II) with 3,6-dichloro-2,6
      dihydroxy-1,4-benzoquinone (chloranilic acid) and 1,10-phenanthroline was
      prepared and characterised by X-ray structure analysis and IR spectroscopy. Three
      complexes exhibit square-pyramidal coordination, whereas one exhibits octahedral
      coordination. The ligand 1,10-phenanthroline acts in a bidentate chelating mode
      with N,N-metal binding. The chloranilate dianion coordinates to the Cu(II) atom
      in a terminal bidentate ortho-quinone-like mode, forming a mononuclear complex
      species. However, in one structure a novel type of coordination mode of
      chloranilate is observed. In addition to the bidentate mode, a monodentate
      bridging mode through a carboxy oxygen of a symmetry-related dianion leads to the
      formation of polymeric coordination ribbon. The crystal packing of penta
      coordinated species, in addition to hydrogen bonding, involves less common
      stacking interactions of chelate rings with the pi-systems of the ligands.

PMID- 24676312
TI  - Five additional macrocycles that allow Na+ ion-templated threading of guest units
      featuring a single urea or amide functionality.
AB  - Five analogues of the macrocycle BPX26C6 are also capable of recognizing single
      urea and/or amide functionalities in the presence of templating Na(+) ions. We
      have unambiguously confirmed the formation of such [2]pseudorotaxane complexes in
      solution through syntheses of the corresponding [2]rotaxanes. 

PMID- 24676313
TI  - Antioxidant effect of zinc supplementation on both plasma and cellular red-ox
      status markers in a group of elderly Italian population.
AB  - OBJECTIVES: The aim of this work was to evaluate the effect of long term
      supplementation with two moderate dose of Zn on plasma and cellular red-ox status
      markers in elderly volunteers. DESIGN, SETTING AND SUBJECTS: In a double blind
      study 108 healthy volunteers, aged 70-85 years, were enrolled. They were randomly
      divided in 3 groups of treatment, receiving placebo, 15 mg/day and 30 mg/day of
      Zn for 6 months. Red-ox status markers were assessed at baseline and after 6
      months evaluating carotenoids, vitamin A and E in plasma; glutathione (GSH),
      thiol groups (RSH), malondialdehyde (MDA), percentage of haemolysis and
      methemoglobin in erythrocytes. RESULTS: Zn supplementation had no significant
      effects on red-ox status markers except for vitamin A levels (from 1.94+/-0.44 to
      2.18+/-0.48 MUM in volunteers receiving 15 mg of Zn and from 1.95+/-0.46 to
      2.26+/-0.56 MUM in volunteers receiving 30 mg of Zn), which increased
      proportionally to zinc dose. CONCLUSIONS: It appears that, differently from
      unhealthy populations, long-term supplementation with two moderate doses of Zn in
      a healthy elderly population, with an adequate Zn nutritive status and macro and
      micronutrients intakes in the range of normality, is an inefficient way to
      increase antioxidant defences.

PMID- 24676314
TI  - Nutritional status and dysphagia risk among community-dwelling frail older
      adults.
AB  - OBJECTIVES: Although the presence of dysphagia is a key determinant of
      nutritional status among older adults, few studies have focused on the
      association between malnutrition and dysphagia risk in community-dwelling frail
      older adults. This study estimated the prevalence of malnutrition and quantified
      the association between malnutrition and dysphagia risk among community-dwelling
      older Japanese adults requiring long-term care. DESIGN: Cross-sectional study.
      SETTING: This study was conducted with the cooperation of the Japan Dental
      Association and local dental associations in all 47 prefectures from January to
      February 2012. PARTICIPANTS: Individuals aged >=65 years capable of oral nutrient
      intake who were living at home and receiving home dental care and treatment.
      MEASUREMENTS: Individual demographic characteristics and factors associated with
      health loss-related functional decline were obtained through interviews by home
      visit dentists and self-administered questionnaires. Nutritional status and
      dysphagia risk were evaluated using the Mini Nutritional Assessment Short Form
      and the Dysphagia Risk Assessment for the Community-dwelling Elderly. RESULTS:
      Among 874 respondents (345 men and 529 women), 24.6% were malnourished, 67.4%
      were at risk of malnutrition, and 8.0% were well nourished. Dysphagia risk was
      related to an increased likelihood of malnutrition at an old age, even after
      adjusting for covariates (PR = 1.30, 95% CI = 1.01-1.67). CONCLUSION:
      Malnutrition is highly prevalent among community-dwelling frail older adults, and
      dysphagia risk is independently associated with malnutrition. Dysphagia may be an
      important predictor of malnutrition progression in aged populations.

PMID- 24676315
TI  - Influence of nutritional status on health-related quality of life of non
      institutionalized older people.
AB  - OBJECTIVES: Health-related quality of life (HRQoL) is a multidimensional health
      measurement and a key to optimal aging. The aim of this study was to examine the
      association of nutritional status with HRQoL in the elderly. DESIGN: Cross
      sectional study. SETTING: Villanueva Older Health Study, a community-based study
      in Villanueva de la Canada (Madrid, Spain). PARTICIPANTS: 83 (53 women) non
      institutionalized inhabitants aged 80 years and above. MEASUREMENT: HRQoL was
      assessed by EuroQoL-5D (EQ-5D) questionnaire, nutritional risk by Mini
      Nutritional Assessment (MNA) questionnaire and dietary intake by 24-hour dietary
      recall. Statistical significance was evaluated at 95% confidence level (P<0.05).
      RESULTS: EQ-5D pointed out differences between men and women (0.782+/-0.235 and
      0.633+/-0.247; p=0.02). Problems in mobility (total sample) and pain/discomfort
      (women) dimensions were most frequently reported. MNA (26.5+/-3.2 men and 24.3+/
      3.2 women; p=0.03) revealed malnutrition in 3.3% of men and 1.9% of women, and
      risk of malnutrition in 6.7% and 37.7%, respectively. Total sample was at risk of
      folic acid, zinc, magnesium, vitamin D and vitamin E deficiency. EQ-5D was
      associated with MNA (p<0.001). EQ-5Dindex was associated with energy intake
      (p=0.04) and EQ-5Dvas was negatively correlated with body mass index (p=0.02). EQ
      5D pain/discomfort dimension was associated with energy (p=0.006), protein
      (p=0.005), lipid (p=0.03), magnesium (p=0.032), phosphorus (p=0.012), selenium
      (p=0.043) and niacin (p=0.004) intake. CONCLUSIONS: Women showed poorer HRQoL and
      higher malnutrition risk. A relationship between HRQoL and risk of malnutrition
      was observed. Results suggest that when energy and protein, lipid, phosphorus,
      magnesium, selenium and niacin intake increase, HRQoL is promoted, although the
      increase does not seem to have a strong direct effect on it. The limited
      influence of energy and nutrient intake on HRQoL observed requires further
      research.

PMID- 24676316
TI  - Validation of the modified mini nutritional assessment short-forms in different
      populations of older people in Poland.
AB  - OBJECTIVE: To assess the usefulness in different populations of elderly people in
      Poland of both modified versions of Mini Nutritional Assessment Short-Forms (MNA
      SFs) with a three-category scoring classification: one using BMI (MNA-SF-BMI) and
      another using calf circumference (MNA-SF-CC). SETTING AND PARTICIPANTS: A group
      of 932 community-dwelling subjects from the urban environment, 812 subjects from
      the rural environment and 859 subjects from an institutional environment (nursing
      homes). MEASUREMENTS: Agreement between both MNA-SFs and the MNA full form.
      RESULTS: MNA-SF-BMI correctly classified 84.12%, 82.51% and 81.84% of subjects
      from urban, rural and institutional environment, respectively. For MNA-SF-CC
      those values were 82.4%, 71.8% and 76.6%, respectively. The sensitivity and
      specificity of MNA-SF-BMI and MNA-SF-CC against full MNA in screening for "at
      risk/malnutrition" and "malnutrition" were generally very high, except for
      relatively lower sensitivity (74.1%) when screening for "malnutrition" with MNA
      SF-CC in nursing homes. CONCLUSION: Both MNA-SFs can be recommended as screening
      tools in assessing the nutritional state of the community-dwelling and
      institutionalised elderly in Poland. The full version of the MNA confirmed the
      results of MNA-SFs in this group. The "classic" MNA-SF using BMI was found to
      perform better than the MNA-SF-CC. The MNA-SF-CC should be used only when
      measuring BMI is not possible. While using MNA-SF-CC in nursing homes, a higher
      MNA-SF-CC cut-point of eleven should be rather used in this population to screen
      for "at risk/malnutrition".

PMID- 24676318
TI  - Impact of body mass index on the relationship between muscle quality and physical
      function in older women.
AB  - OBJECTIVES: To investigate the impact of body mass index (BMI) (normal weight,
      overweight, obese) on the relationship between muscle quality (MQ) and physical
      function in community-dwelling older women. DESIGN: Cross-sectional study.
      SETTING: University research laboratory. PARTICIPANTS: Community-dwelling older
      women (n = 94, 73.6 +/- 5.4 y) stratified by BMI (normal weight: 20.0-24.9 kg/m2;
      overweight: 25.0-29.9 kg/m2; obese: >= 30.0 kg/m2). MEASUREMENTS: Body mass index
      using height and weight, leg extension power via the Nottingham power rig, body
      composition using dual-energy X-ray absorptiometry, and physical function (6
      minute walk, 8-foot up-and-go, 30-second chair stand). Muscle quality was defined
      as leg power (watts) normalized for lower-body mineral-free lean mass (kg).
      RESULTS: Following adjustments for covariates, muscle quality was significantly
      higher in women of normal BMI compared to overweight (10.0 +/- 0.4 vs. 8.7 +/-
      0.4 watts/kg, p = 0.03). Muscle quality was a significant predictor of
      performance on the 6-minute walk and 8-foot up-and-go in normal and overweight
      women (all p < 0.05) and performance on the 30-second chair stand in normal and
      obese women (both p < 0.05). Body mass index did not significantly impact the
      association between MQ and physical function (all p > 0.05). CONCLUSIONS: Muscle
      quality varies by BMI, yet the relationship to physical function is not
      significantly different across BMI groups. The results imply that interventions
      that increase MQ in older women may improve physical function, regardless of BMI.

PMID- 24676317
TI  - Factors associated with deterioration of mini nutritional assessment-short form
      status of nursing home residents during a 2-year period.
AB  - OBJECTIVE: A number of other studies have been conducted to verify the Mini
      Nutritional Assessment (MNA) or the MNA short form (MNA-SF) as a nutritional
      assessment/screening tool in various clinical settings or communities. However,
      there are few longitudinal studies using these tools to analyze which factors
      affect the incidence of deteriorating nutritional status. We tried to identify
      the factors associated with deterioration of MNA-SF status of nursing home
      residents during a 2-year period. METHODS: Participants were 392 people with a
      mean age of 84.3 in 12 nursing homes in Japan. The factors associated with
      deterioration in MNA-SF categories during the study period compared to
      stable/improved MNA-SF categories were identified. RESULTS: At baseline, 19.9% of
      the participants were malnourished and 60.2% were at risk of malnutrition,
      according to the MNA-SF classification. After 2 years, 66.3% participants
      maintained and 6.1% participants improved their nutritional status according to
      the MNA-SF classification, while 27.6% showed deterioration in MNA-SF status.
      Stepwise logistic-regression procedure indicated that basic ADL impairment and
      hospitalization during the follow-up period were associated with declining MNA-SF
      status. CONCLUSIONS: Poor basic ADL status and hospitalization during the follow
      up period were associated with malnutrition and risk of malnutrition as assessed
      by MNA-SF of nursing homes residents during a 2-year period.

PMID- 24676320
TI  - Perception of Alzheimer's disease in the French population.
AB  - OBJECTIVE: The aim of this study was to investigate the perception, knowledge,
      opinions and beliefs about AD in the French population to improve care for
      patients with Alzheimer's disease. DESIGN: A cross-sectional telephone survey in
      2008. SETTING: French "Alzheimer Plan 2008-2012". PARTICIPANTS: 2013 respondents,
      representative of the French population. MEASUREMENTS: The respondents answered a
      questionnaire in which they were presented with a series of attitudinal
      statements about health in general and AD. RESULTS: Main results are summarized
      as followed: (a) Respondents think that AD can be devastating for a family (93%).
      This devastating feeling prevails in the population >75 years old and in people
      who know patient with AD. (b) General population has a reasonable knowledge about
      AD, but is still unable to recognize early stages: 95% of respondents considered
      that difficulties to manage administrative papers and find their way back home
      suggest early AD. (c) 91% of the population would like to know the diagnosis if
      they had AD. (d) 38% of the population know or have known at least one patient
      within their social circle. People think that the care of AD's patient can be
      better but they trust in the French government to improve it. CONCLUSION: General
      representation of AD is changing in a positive way and, even though AD is
      perceived as a calamity, people are confident that solutions will be found in the
      future.

PMID- 24676319
TI  - Current evidence for the use of coffee and caffeine to prevent age-related
      cognitive decline and Alzheimer's disease.
AB  - Although nothing has been proven conclusively to protect against cognitive aging,
      Alzheimer's disease or related dementias, decades of research suggest that
      specific approaches including the consumption of coffee may be effective. While
      coffee and caffeine are known to enhance short-term memory and cognition, some
      limited research also suggests that long-term use may protect against cognitive
      decline or dementia. In vitro and pre-clinical animal models have identified
      plausible neuroprotective mechanisms of action of both caffeine and other
      bioactive components of coffee, though epidemiology has produced mixed results.
      Some studies suggest a protective association while others report no benefit. To
      our knowledge, no evidence has been gathered from randomized controlled trials.
      Although moderate consumption of caffeinated coffee is generally safe for healthy
      people, it may not be for everyone, since comorbidities and personal genetics
      influence potential benefits and risks. Future studies could include short-term
      clinical trials with biomarker outcomes to validate findings from pre-clinical
      models and improved epidemiological studies that incorporate more standardized
      methods of data collection and analysis. Given the enormous economic and
      emotional toll threatened by the current epidemic of Alzheimer's disease and
      other dementias, it is critically important to validate potential prevention
      strategies such as coffee and caffeine. 

PMID- 24676321
TI  - Plasma vitamin D levels and cognitive function in aging women: the nurses' health
      study.
AB  - BACKGROUND: Vitamin D may play a role in preserving cognitive function. However,
      there is a paucity of prospective studies on the relationship between vitamin D
      and cognition with aging. The aim of this study was to examine the association
      between plasma levels of vitamin D and subsequent cognitive function. METHODS:
      This is a prospective study including 1,185 women aged 60-70 years from the
      Nurses' Health Study, who had plasma 25-hydroxy-vitamin D levels measured in 1989
      1990 and completed an initial Telephone Interview of Cognitive Status
      approximately 9 years later. Subsequently, three follow-up cognitive assessments
      were conducted at 1.5-2.0 years intervals. We used multivariable-adjusted linear
      regression to model initial cognitive function, and mixed linear regression to
      model change in cognitive function over time. RESULTS: Lower vitamin D levels
      were associated with significantly worse cognitive function 9 years later. For
      example, the mean global composite score averaging all the cognitive tests was
      0.20 lower (95% Confidence Interval (CI):-0.33,-0.08; p-trend=0.009) in women in
      the lowest quintile (median=14.1 ng/mL) compared with women in the highest
      quintile of vitamin D (median=38.4 ng/mL). The observed differences were
      equivalent to the effect estimates we found for women who were approximately 4-6
      years apart in age. However, vitamin D levels were not significantly associated
      with subsequent cognitive decline during 6 years of follow-up. CONCLUSIONS:
      Higher levels of plasma vitamin D in women aged 60-70 years were associated with
      better cognitive function about a decade later but were not associated with
      cognitive decline during 6 years of follow-up.

PMID- 24676322
TI  - Relation between caffeine and behavioral symptoms in elderly patients with
      dementia: an observational study.
AB  - OBJECTIVES: Caffeine is known to improve concentration and reduce fatigue in
      healthy adults, but high doses may induce anxiety and agitation. Because the
      effects of caffeine in elderly people with dementia are unknown, this study
      explores the relation between caffeine and behavioral symptoms in a group of
      elderly patients with dementia. DESIGN: An observational pilot study. SETTING: A
      dementia special care unit of a Dutch nursing home. PARTICIPANTS: A total of 29
      elderly patients with dementia. MEASUREMENTS: Behavioral symptoms were measured
      with the NPI-NH, and sleep and caffeine consumption were measured using
      questionnaires. RESULTS: A significant relation was found between the total
      amount of caffeine consumed during the day and apathy [Kendall's tau (KT) -0.287
      p=0.03], and the number of times that participants got up at night (KT 0.462; p
      <0.01). The amount of caffeine consumed after 6 p.m. was also significantly
      related to the number of times participants got up at night (KT 0.436; p <0.01).
      Multilevel analysis showed caffeine to be negatively correlated with aberrant
      motor behavior [b = -0.47 (0.22), Wald (461) = -2.12, p=0.03] and apathy [b = 
      0.88 (0.45), Wald (461)= -1.96, p=0.05], and showed a significant relation
      between caffeine consumption after 6 p.m. and the number of times participants
      got up at night [b=0.48 (0.22), Wald (461)= 2.20, p=0.03]. CONCLUSION: This study
      established an association between caffeine consumption and behavioral symptoms
      in elderly patients with moderately severe dementia. Therefore, adjusting
      caffeine consumption could be part of an interdisciplinary approach to behavioral
      symptoms, particularly when aberrant motor behavior, apathy or sleeping
      difficulties are involved. These results indicate that further research on the
      effects of caffeine on behavioral symptoms in dementia is warranted.

PMID- 24676323
TI  - Mediterranean diet and functional indicators among older adults in non
      Mediterranean and Mediterranean countries.
AB  - BACKGROUND/OBJECTIVES: The Mediterranean diet (MEDDIET) has been shown to be
      related to longevity. This study aimed to determine the association between
      adherence to MEDDIET and physical function of older adults in the United-States
      and Israel. METHODS: Data from the US National Health and Nutrition Survey
      (NHANES) 1999-2002 and from the Israeli National Health and Nutrition Survey
      (MABAT ZAHAV) 2005-2006 were used. Participants with nutritional and functional
      data were included. Adherence to the MEDDIET was assessed by a 9-unit score
      (MDS). RESULTS: Among 2791 NHANES and 1786 MABAT ZAHAV participants, mean
      age=71.2 y and 74.9 y, 20% and 27% had low MDS (0-2), 66% and 62% had a medium
      score (3-5), and 14% and 11% had a high score (6-9), respectively. Higher MDS was
      associated with higher education and better lifestyle behaviors. Cognitive and
      physical functions were significantly better in NHANES and MABAT ZAHAV among the
      highest MDS. In NHANES, MDS (high vs. low) was associated with faster walking
      speed after adjusting for confounders in a logistic regression model [Odds Ratio
      (OR)=0.71, P=0.034, Cl 95% 0.511-0.974]. When cognitive function was added, the
      association was attenuated (OR=0.75, P=0.093, Cl 95% 0.540-1.049). In MABAT
      ZAHAV, in a logistic regression model adjusted among other to cognitive function,
      MDS (high vs. low) was associated with fewer disabilities (OR=0.51, P=0.029, Cl
      95% 0.276-0.934). CONCLUSIONS: Adherence to the MEDDIET is associated with better
      health characteristics and better functioning. Further cohort and intervention
      studies may shed light on temporal and causal relationships between MEDDIET and
      these parameters.

PMID- 24676324
TI  - Relationship between use of proton pump inhibitors and IGF system in older
      subjects.
AB  - OBJECTIVES: to investigate the effects of proton pump inhibitors (PPIs) on the
      insulin-like-growth factor 1(IGF-1) system in the elderly. DESIGN: cross
      sectional. SETTING: InCHIANTI study. PARTICIPANTS: 938 older subjects (536 women,
      402 men, mean age 75.7+/-7.4 years). MEASUREMENTS: complete data on age, sex,
      BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1
      and -3 (IGFBP-1, IGFBP-3). RESULTS: Participants were categorized by PPI use,
      identifying 903 PPI non users and 35 users. After adjusting for age, male PPI
      users (107.0 +/- 69.6 vs. 127.1 +/- 55.8, p<0.001) and female PPI users (87.6 +/-
      29.1 vs. 107.6 +/- 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1
      levels were similar in the two groups in both sexes. In whole population, after
      adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1-113.8]
      than non-users 110 [77.8-148.6], p=0.02. After further adjustment for BMI,
      albumin, liver function, C-reactive protein, Interleukin-6, number of
      medications, ACE-inhibitors use, caloric intake, protein intake, physical
      activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and
      negatively associated with IGF-1 levels (beta+/-SE = -19.60+/-9.83, p=0.045).
      CONCLUSION: Use of PPIs was independently and negatively associated with IGF-1
      levels.

PMID- 24676325
TI  - Inverted CD4:CD8 ratio is not associated with three-year mortality in a sample of
      community-dwelling oldest old: the OCTABAIX immune study.
AB  - BACKGROUND: The presence of an immune risk phenotype (IRP) has been correlated
      with survival rates in elderly people. OBJECTIVE: To determine whether an
      inverted CD4:CD8 ratio might be a marker of IRP in a sample of oldest old by
      assessing its relationship with mortality. DESIGN: Prospective cohort study.
      SETTING: Community-based survey study of seven primary healthcare centres.
      PARTICIPANTS: 328 people born in 1924 and registered with primary healthcare
      centres. MEASUREMENTS: Chronic drug prescription, functional status (Barthel and
      Lawton indexes) and cognitive status (Spanish version of the Mini-Mental State
      Examination) were recorded. CD4:CD8 ratios were determined, with a ratio of 1.00
      or less being used to define IRP. RESULTS: The CD4:CD8 ratio was 1.00 or less in
      47 subjects (15.6%). After three years, 51 subjects had died (16.3%); 9 were from
      among the 47 (19.1%) with an inverted CD4:CD8 ratio and 42 (15.8%) from the
      remainder (P=0.52). Multivariate analysis identified two significant clinical
      variables (Lawton Index scores and the number of chronic drugs prescribed) as
      being independent predictors of three-year mortality risk in this cohort of
      octogenarians. This risk profile did not change when introducing the CD4:CD8
      ratio into the calculation. CONCLUSION: In this community-dwelling population of
      oldest old (85 years old at baseline) an inverted CD4:CD8 ratio was not
      associated with three-year mortality.

PMID- 24676326
TI  - Patterns of chronic co-morbid medical conditions in older residents of U.S.
      nursing homes: differences between the sexes and across the agespan.
AB  - OBJECTIVE: There are limited data on combinations of co-morbid conditions to
      guide efforts to improve therapeutic strategies in patients with multiple co
      morbid conditions. To some extent, this may be due to limited data on
      combinations of co-morbid conditions in patient groups. Our goal was to determine
      the most common co-morbid medical conditions in older residents of U.S. nursing
      homes and identify sex differences in prevalences and changes across the agespan
      of nursing residents. DESIGN: Cross sectional analysis of National Nursing Home
      Survey (NNHS)--a nationally representative sample with comprehensive medical data
      on nursing home residents. SETTING: 1174 Nursing homes. PARTICIPANTS: Long term
      stay residents of U.S. Nursing Homes aged 65 years and older (11,734 :8745 women,
      2989 men). MEASUREMENTS: Determination of the prevalences of the most frequent
      two and three disease combinations identified using Clinical Classifications
      Software (CCS) for ICD-9-CM and a composite vascular disease diagnosis
      (atherosclerosis and/or coronary artery disease, and/or peripheral arterial
      disease, and/or cerebrovascular disease or stroke) from the most recent and only
      NNHS survey with comprehensive medical diagnosis information. RESULTS: Frequent 2
      disease combinations were: hypertension (HTN) + dementia (DEM) in 27%, HTN + any
      Vascular (Vasc) disease (26%), HTN + depression(DEP) 21%, HTN + arthritis(ARTH)
      20%, DEM + Vasc (21%), DEM+Depression 19%, Arthritis + DEM 17%, DEP + Vasc (16%),
      ARTH + Vasc (15%), followed by HTN + GERD (14%) and ARTH + DEP (14%). Frequent 3
      disease combinations: HTN +VASC+ DEP in 13%, HTN +DEM +DEP (11%), and
      HTN+Arthritis+DEM (10%). HTN was in 80% of the top 3-disease combinations, Vasc
      in 50%, HTN+VASC in 35%, DEM or DEP in 40%, ARTH in 25% and GERD in 20%.
      Combinations with anemia, arthritis, dementia, heart failure, osteroporosis,
      thyroid disease were higher in women, COPD combinations higher in men. As age
      increased, dementia, depression, arthritis, and anemia with hypertension were
      common co-morbid combinations, diabetes and heart failure were not. CONCLUSIONS:
      Hypertension, vascular disease, dementia, arthritis, depression, and gastro
      esophageal reflux disease were part of the most prevalent co-morbid conditions.
      Multimorbidity patterns can be identified in nursing home residents and vary with
      age and by sex.

PMID- 24676327
TI  - Preoperative oral supplementation support in patients with esophageal cancer.
AB  - OBJECTIVE: Surgeries for cancer of the esophagus are still associated with a high
      rate of postoperative morbidity. There are few reports of perioperative
      nutritional support for patients undergoing esophageal cancer surgery, and there
      is insufficient evidence to recommend routine use of immunonutrition in these
      patients. The aim of this study was to determine whether preoperative
      immunonutrition positively influences key clinical outcomes such as postoperative
      infectious complications, mortality, length of hospital stay, and short-term
      survival in this population. DESIGN AND SETTING: We undertook a retrospective
      investigation of the effects of preoperative nutritional support on the
      postoperative course of esophageal cancer surgery at the Department of
      Gastroenterological Surgery, International University of Health and Welfare Mita
      Hospital, Tokyo, Japan. PARTICIPANTS: Fifty-five patients who underwent
      esophagectomy for esophageal cancer were included in this study. Of the 55
      patients, 26 patients consumed a liquid dietary supplement (IMPACT group) before
      surgery and 29 patients did not (STANDARD group). INTERVENTION: Before surgery,
      the IMPACT group consumed 750 ml (3 packs)/day of Impact for 5 consecutive days.
      MEASUREMENTS: The analysis was based on postoperative complications, hospital
      mortality, length of hospital stay, and short-term survival. RESULTS:
      Significantly fewer patients developed postoperative infections in the IMPACT
      group compared with the STANDARD group (p=.007): 4 of 21 patients in the IMPACT
      group and 10 of 29 patients in the STANDARD group. Either an infectious
      complication or another complication developed in 8 patients in the IMPACT group
      and 13 patients in the STANDARD group, with the result that 6 patients in the
      STANDARD group died of postoperative complications (p=.001). The duration of
      hospitalization was 34 days in the IMPACT group and 48 days in the STANDARD
      group; hence, hospitalization was significantly shorter in patients treated with
      Impact (p=.008). The mean 6-month survival rates for the IMPACT group and the
      STANDARD group were 92% (24/26) and 72% (21/29), respectively (p=.028).
      CONCLUSION: Simple preoperative supplementation significantly improved outcome.
      Administration of the supplemental diet before esophageal surgery appeared to be
      an effective strategy in reducing infectious complications, mortality, and
      hospitalization, and improving short-term survival.

PMID- 24676329
TI  - Hypovitaminosis D: which oral supplement therapy?
AB  - OBJECTIVES: the possible therapeutic role of vitamin D in different kind of
      diseases explains the growing interest in this vitamin due to its pleiotropic
      effects. This short report shows preliminary results of prevalence of
      hypovitaminosis D in a group of patients and proposes a oral supplement therapy
      effective in correcting hypovitaminosis in a short time, without side effects.
      METHODS: 243 patients (aged 26-93; 67 males) were enrolled at this study. We
      evaluated plasma levels of 25-hydroxyvitamin D [25(OH)D] with the following cut
      off values: <10 ng/ml or <0-25 nmol/L (deficient), 10-30 ng/ml or 25-75 nmol/L 30
      50 (insufficient) and > 30 ng/ml or > 50 nmol/L (normal). The first 73 patients
      with hypovitaminosis D received at baseline 25,000 IU (Cholecalciferol) per os
      twice a month (Tp.A). The next patients (Tp.B) at baseline received a loading
      dose of 50,000 IU once a week for 8 weeks, followed by a maintenance dose of
      25,000 IU twice a month. RESULTS: hypovitaminosis D is a widespread condition
      (i.e., 82.3%) not only in elderly (75.6% of 75 patients aged <65 yrs and 86.5% of
      168 subjects aged >65 yrs). Preliminary results at 6 months show that Tp.B is
      more effective in correcting hypovitaminosis D (baseline 14.4 +/- 5.3 ng/ml; 24
      wk 43.3 +/- 14.7 ng/ml; p<0.0001). CONCLUSION: hypovitaminosis D is an important
      public health problem. We believe it is important to quickly achieve normal Vit.
      D plasma values in order to produce pleiotropic effects.

PMID- 24676328
TI  - An overview of structure, mechanical properties, and treatment for age-related
      tendinopathy.
AB  - Tendons transfer tensile loads from muscle to bone, which enable joint motions
      and stabilize joints. Tendons sustain large mechanical loads in vivo and as a
      result, tendons were frequently injured. Aging has been confirmed as a
      predisposing factor of tendinopathy and bad recovery quality following tendon
      repair. Current treatment methods are generally not effective and involve either
      symptomatic relief with non-steroidal antiinflammatory drugs and physical therapy
      or surgery when conservative treatments failed. The limitation in treatment
      options is due to our incomplete knowledge of age-related tendinopathy. Studies
      over the past decades have uncovered a number of important mechanical and
      cellular changes of aging tendon. However, the basis of aging as a major risk
      factor for tendon injury and impaired tendon healing remained poorly understood.
      The objectives of this review are to provide an overview of the current knowledge
      about the aging-associated changes of structure, mechanical properties and
      treatment in tendon and highlight causes and therapies for age-related
      tendinopathy. 

PMID- 24676330
TI  - Mapping of imprinted quantitative trait loci using immortalized F2 populations.
AB  - Mapping of imprinted quantitative trait loci (iQTLs) is helpful for understanding
      the effects of genomic imprinting on complex traits in animals and plants. At
      present, the experimental designs and corresponding statistical methods having
      been proposed for iQTL mapping are all based on temporary populations including
      F2 and BC1, which can be used only once and suffer some other shortcomings
      respectively. In this paper, we propose a framework for iQTL mapping, including
      methods of interval mapping (IM) and composite interval mapping (CIM) based on
      conventional low-density genetic maps and point mapping (PM) and composite point
      mapping (CPM) based on ultrahigh-density genetic maps, using an immortalized F2
      (imF2) population generated by random crosses between recombinant inbred lines or
      doubled haploid lines. We demonstrate by simulations that imF2 populations are
      very desirable and the proposed statistical methods (especially CIM and CPM) are
      very powerful for iQTL mapping, with which the imprinting effects as well as the
      additive and dominance effects of iQTLs can be unbiasedly estimated. 

PMID- 24676331
TI  - Application of nitrogen and carbon stable isotopes (delta(15)N and delta(13)C) to
      quantify food chain length and trophic structure.
AB  - Increasingly, stable isotope ratios of nitrogen (delta(15)N) and carbon
      (delta(13)C) are used to quantify trophic structure, though relatively few
      studies have tested accuracy of isotopic structural measures. For laboratory
      raised and wild-collected plant-invertebrate food chains spanning four trophic
      levels we estimated nitrogen range (NR) using delta(15)N, and carbon range (CR)
      using delta(13)C, which are used to quantify food chain length and breadth of
      trophic resources respectively. Across a range of known food chain lengths we
      examined how NR and CR changed within and between food chains. Our isotopic
      estimates of structure are robust because they were calculated using resampling
      procedures that propagate variance in sample means through to quantified
      uncertainty in final estimates. To identify origins of uncertainty in estimates
      of NR and CR, we additionally examined variation in discrimination (which is
      change in delta(15)N or delta(13)C from source to consumer) between trophic
      levels and among food chains. delta(15)N discrimination showed significant
      enrichment, while variation in enrichment was species and system specific, ranged
      broadly (1.40/00 to 3.30/00), and importantly, propagated variation to subsequent
      estimates of NR. However, NR proved robust to such variation and distinguished
      food chain length well, though some overlap between longer food chains infers a
      need for awareness of such limitations. delta(13)C discrimination was
      inconsistent; generally no change or small significant enrichment was observed.
      Consequently, estimates of CR changed little with increasing food chain length,
      showing the potential utility of delta(13)C as a tracer of energy pathways. This
      study serves as a robust test of isotopic quantification of food chain structure,
      and given global estimates of aquatic food chains approximate four trophic levels
      while many food chains include invertebrates, our use of four trophic level plant
      invertebrate food chains makes our findings relevant for a majority of ecological
      systems.

PMID- 24676333
TI  - Floral reward, advertisement and attractiveness to honey bees in dioecious Salix
      caprea.
AB  - In dioecious, zoophilous plants potential pollinators have to be attracted to
      both sexes and switch between individuals of both sexes for pollination to occur.
      It often has been suggested that males and females require different numbers of
      visits for maximum reproductive success because male fertility is more likely
      limited by access to mates, whereas female fertility is rather limited by
      resource availability. According to sexual selection theory, males therefore
      should invest more in pollinator attraction (advertisement, reward) than females.
      However, our knowledge on the sex specific investment in floral rewards and
      advertisement, and its effects on pollinator behaviour is limited. Here, we use
      an approach that includes chemical, spectrophotometric, and behavioural studies
      i) to elucidate differences in floral nectar reward and advertisement (visual,
      olfactory cues) in dioecious sallow, Salix caprea, ii) to determine the relative
      importance of visual and olfactory floral cues in attracting honey bee
      pollinators, and iii) to test for differential attractiveness of female and male
      inflorescence cues to honey bees. Nectar amount and sugar concentration are
      comparable, but sugar composition varies between the sexes. Olfactory sallow cues
      are more attractive to honey bees than visual cues; however, a combination of
      both cues elicits the strongest behavioural responses in bees. Male flowers are
      due to the yellow pollen more colourful and emit a higher amount of scent than
      females. Honey bees prefer the visual but not the olfactory display of males over
      those of females. In all, the data of our multifaceted study are consistent with
      the sexual selection theory and provide novel insights on how the model organism
      honey bee uses visual and olfactory floral cues for locating host plants. 

PMID- 24676334
TI  - Iatrogenic occlusion of the ophthalmic artery after cosmetic facial filler
      injections: a national survey by the Korean Retina Society.
AB  - IMPORTANCE: Iatrogenic occlusion of the ophthalmic artery and its branches is a
      rare but devastating complication of cosmetic facial filler injections.
      OBJECTIVE: To investigate clinical and angiographic features of iatrogenic
      occlusion of the ophthalmic artery and its branches caused by cosmetic facial
      filler injections. DESIGN, SETTING, AND PARTICIPANTS: Data from 44 patients with
      occlusion of the ophthalmic artery and its branches after cosmetic facial filler
      injections were obtained retrospectively from a national survey completed by
      members of the Korean Retina Society from 27 retinal centers. Clinical features
      were compared between patients grouped by angiographic findings and injected
      filler material. MAIN OUTCOMES AND MEASURES: Visual prognosis and its
      relationship to angiographic findings and injected filler material. RESULTS:
      Ophthalmic artery occlusion was classified into 6 types according to angiographic
      findings. Twenty-eight patients had diffuse retinal and choroidal artery
      occlusions (ophthalmic artery occlusion, generalized posterior ciliary artery
      occlusion, and central retinal artery occlusion). Sixteen patients had localized
      occlusions (localized posterior ciliary artery occlusion, branch retinal artery
      occlusion, and posterior ischemic optic neuropathy). Patients with diffuse
      occlusions showed worse initial and final visual acuity and less visual gain
      compared with those having localized occlusions. Patients receiving autologous
      fat injections (n = 22) had diffuse ophthalmic artery occlusions, worse visual
      prognosis, and a higher incidence of combined brain infarction compared with
      patients having hyaluronic acid injections (n = 13). CONCLUSIONS AND RELEVANCE:
      Clinical features of iatrogenic occlusion of the ophthalmic artery and its
      branches following cosmetic facial filler injections were diverse according to
      the location and extent of obstruction and the injected filler material.
      Autologous fat injections were associated with a worse visual prognosis and a
      higher incidence of combined cerebral infarction. Extreme caution and care should
      be taken during these injections, and physicians should be aware of a diverse
      spectrum of complications following cosmetic facial filler injections.

PMID- 24676335
TI  - Monocytic cells become less compressible but more deformable upon activation.
AB  - AIMS: Monocytes play a significant role in the development of atherosclerosis.
      During the process of inflammation, circulating monocytes become activated in the
      blood stream. The consequent interactions of the activated monocytes with the
      blood flow and endothelial cells result in reorganization of cytoskeletal
      proteins, in particular of the microfilament structure, and concomitant changes
      in cell shape and mechanical behavior. Here we investigate the full elastic
      behavior of activated monocytes in relation to their cytoskeletal structure to
      obtain a better understanding of cell behavior during the progression of
      inflammatory diseases such as atherosclerosis. METHODS AND RESULTS: The recently
      developed Capillary Micromechanics technique, based on exposing a cell to a
      pressure difference in a tapered glass microcapillary, was used to measure the
      deformation of activated and non-activated monocytic cells. Monitoring the
      elastic response of individual cells up to large deformations allowed us to
      obtain both the compressive and the shear modulus of a cell from a single
      experiment. Activation by inflammatory chemokines affected the cytoskeletal
      organization and increased the elastic compressive modulus of monocytes with 73
      340%, while their resistance to shape deformation decreased, as indicated by a 25
      88% drop in the cell's shear modulus. This decrease in deformability is
      particularly pronounced at high strains, such as those that occur during
      diapedesis through the vascular wall. CONCLUSION: Overall, monocytic cells become
      less compressible but more deformable upon activation. This change in mechanical
      response under different modes of deformation could be important in understanding
      the interplay between the mechanics and function of these cells. In addition, our
      data are of direct relevance for computational modeling and analysis of the
      distinct monocytic behavior in the circulation and the extravascular space.
      Lastly, an understanding of the changes of monocyte mechanical properties will be
      important in the development of diagnostic tools and therapies concentrating on
      circulating cells.

PMID- 24676338
TI  - Variation in chlorophyll content per unit leaf area in spring wheat and
      implications for selection in segregating material.
AB  - Reduced levels of leaf chlorophyll content per unit leaf area in crops may be of
      advantage in the search for higher yields. Possible reasons include better light
      distribution in the crop canopy and less photochemical damage to leaves absorbing
      more light energy than required for maximum photosynthesis. Reduced chlorophyll
      may also reduce the heat load at the top of canopy, reducing water requirements
      to cool leaves. Chloroplasts are nutrient rich and reducing their number may
      increase available nutrients for growth and development. To determine whether
      this hypothesis has any validity in spring wheat requires an understanding of
      genotypic differences in leaf chlorophyll content per unit area in diverse
      germplasm. This was measured with a SPAD 502 as SPAD units. The study was
      conducted in series of environments involving up to 28 genotypes, mainly spring
      wheat. In general, substantial and repeatable genotypic variation was observed.
      Consistent SPAD readings were recorded for different sampling positions on
      leaves, between different leaves on single plant, between different plants of the
      same genotype, and between different genotypes grown in the same or different
      environments. Plant nutrition affected SPAD units in nutrient poor environments.
      Wheat genotypes DBW 10 and Transfer were identified as having consistent and
      contrasting high and low average SPAD readings of 52 and 32 units, respectively,
      and a methodology to allow selection in segregating populations has been
      developed. 

PMID- 24676336
TI  - Breast cancer cells are arrested at different phases of the cell cycle following
      the re-expression of ARHI.
AB  - ARHI is a maternally imprinted tumor suppressor gene that is expressed in normal
      breast epithelial cells but not in most breast cancer cells. Aberrant methylation
      and hypernomic histone deacetylation have been implicated in the silencing of
      ARHI. To investigate the mechanism of ARHI induction, MDA-MB-231 breast cancer
      cells were either transfected with the eukaryotic expression vector, pcDNA3.1(+)
      ARHI, or were simultaneously treated with a histone deacetylase inhibitor,
      [trichostatin A, (TSA)] and the methyltransferase inhibitor, 5-aza-2'
      deoxycytidine (DAC). The latter treatment group also included the targeting of
      ARHI by small interfering RNA (siRNA) to further examine interactions between
      ARHI and the drugs applied. Levels of ARHI were detected by western blotting, MTT
      assays were used to evaluate cell proliferation, and both cell cycle progression
      and apoptosis were detected using flow cytometry. Both the transfection of
      pcDNA3.1(+)-ARHI and the application of TSA+DAC induced the expression of ARHI.
      Furthermore, reduced cell proliferation, cell cycle arrest and enhanced apoptosis
      were observed for both groups compared to controls. However, a G1/S cell cycle
      arrest was observed for the pcDNA3.1(+)-ARHI group, while a G2 cell cycle arrest
      was observed for the TSA+DAC group. The latter effect was reversed with the
      introduction of ARHI-targeted siRNA in combination with TSA+DAC treatment. To
      further clarify these observations, expression levels of several key cell cycle
      regulators were analyzed by western blotting. The pcDNA3.1(+)-ARHI group
      exhibited higher expression levels of p53, p21 and p27, and lower levels of
      cyclin D1, CDK4 and CDK6 when compared to the control group (P<0.05). For the
      TSA+DAC group, higher levels of p53, p21, cyclin B1 and Chk1 were detected,
      concomitant with lower levels of CDK1, when compared to the control group. Taken
      together, these results suggest that ARHI acts as a tumor suppressor gene in MDA
      MB-231 cells and, although TSA+DAC can block the cells at different cell cycle
      phage, the antitumor effect is ARHI-dependent.

PMID- 24676339
TI  - Chemical applications carried out by local pair natural orbital based coupled
      cluster methods.
AB  - The scope of this review is to provide a brief overview of the chemical
      applications carried out by local pair natural orbital coupled-electron pair and
      coupled-cluster methods. Benchmark tests reveal that these methods reproduce,
      with excellent accuracy, their canonical counterparts. At the same time, the
      speed up achieved by exploiting the locality of the electron correlation permits
      us to tackle chemical systems that, due to their size, would normally only be
      addressable with density functional theory. This review covers a broad variety of
      the chemical applications e.g. simulation of transition metal catalyzed
      reactions, estimation of weak interactions, and calculation of lattice properties
      in molecular crystals. This demonstrates that modern implementations of
      wavefunction-based correlated methods are playing an increasingly important role
      in applied computational chemistry. 

PMID- 24676332
TI  - Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of
      obese subjects and in obesity-associated cancer cells.
AB  - Obesity confers an increased risk of developing specific cancer forms. Although
      the mechanisms are unclear, increased fat cell secretion of specific proteins
      (adipokines) may promote/facilitate development of malignant tumors in obesity
      via cross-talk between adipose tissue(s) and the tissues prone to develop cancer
      among obese. We searched for novel adipokines that were overexpressed in adipose
      tissue of obese subjects as well as in tumor cells derived from cancers commonly
      associated with obesity. For this purpose expression data from human adipose
      tissue of obese and non-obese as well as from a large panel of human cancer cell
      lines and corresponding primary cells and tissues were explored. We found
      expression of ceruloplasmin to be the most enriched in obesity-associated cancer
      cells. This gene was also significantly up-regulated in adipose tissue of obese
      subjects. Ceruloplasmin is the body's main copper carrier and is involved in
      angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is
      produced and secreted at increased rates in obesity. In the obese state, adipose
      tissue contributed markedly (up to 22%) to the total circulating protein level.
      In summary, we have through bioinformatic screening identified ceruloplasmin as a
      novel adipokine with increased expression in adipose tissue of obese subjects as
      well as in cells from obesity-associated cancers. Whether there is a causal
      relationship between adipose overexpression of ceruloplasmin and cancer
      development in obesity cannot be answered by these cross-sectional comparisons. 

PMID- 24676340
TI  - TNF-alpha promotes gallbladder cancer cell growth and invasion through autocrine
      mechanisms.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be a putative tumor
      promoter gene, and autocrine of TNF-alpha expression has been found in colon
      cancer and ovarian cancer. As the role of autocrine TNF-alpha in human
      gallbladder cancer has not yet been elucidated, the present study examined the
      expression of TNF-alpha in gallbladder cancer-derived cell lines. Based on the
      data, TNF-alpha mRNA and TNF-alpha protein expression differed significantly
      different between the cell lines. In addition, using siRNA targeting TNF-alpha,
      the vector, pGPU-GFP-siTNF-alpha, was constructed and then transfected into the
      SGC-996 cells (gallbladder cancer cell line) which express high levels of
      endogenous TNF-alpha. In vitro experiments indicated that the silencing of TNF
      alpha in the SGC-996 cells significantly suppressed proliferation and invasion.
      However, apoptosis was not induced by the silencing of TNF-alpha. Furthermore, we
      traced the mechanisms underlying these effects and found that the silencing of
      TNF-alpha affected the TNF-alpha-AKT-NF-kappaB-Bcl-2 pathway in the SGC-996
      cells. Our data provide evidence that autocrine TNF-alpha plays a role as a tumor
      promoter gene in gallbladder cancer cells, possibly by promoting proliferation
      and invasion through autocrine mechanisms.

PMID- 24676341
TI  - What matters most in pediatric familial hypercholesterolemia, genotype or
      phenotype?

PMID- 24676342
TI  - Dicyanovinyl substituted triarylboranes: a rational approach to distinguish
      fluoride and cyanide ions.
AB  - Two new dicyanovinyl (DCV) functionalized triarylboranes (Mes2B-pi-spacer-DCV,
      for 1: pi-spacer = C6H4, for 2: pi-spacer = 2,3,5,6-tetramethyl-phenyl) are
      reported. The molecular structures of 1 and 2 are similar except for the spacer
      which connects the boryl and DCV units. This small structural perturbation
      induces drastic changes in the optical properties of 1 and 2. Compound 2 shows
      weak dual fluorescence emission in nonpolar solvents and a stronger emission in
      polar solvents. Compound 1 is weakly fluorescent in polar environments but shows
      an intense single luminescence peak in less polar environments. Compound 1
      exhibits a turn-off fluorescence response for both fluoride and cyanide: in
      contrast, 2 shows a turn on fluorescence response for both anions with different
      fluorescence signatures. The NMR titration studies reveal that for compound 2,
      fluoride binds to the boron centre and cyanide binds to the DCV unit. For
      compound 1, the fluoride ion binds to the boron center, whereas the CN(-) binds
      to both the Ar3B and DCV units. 

PMID- 24676343
TI  - How does the dehydration change the host-guest association under homogeneous and
      heterogeneous conditions?
AB  - In this study, the thermodynamic properties of association of some inorganic ions
      (ClO4(-) and SO4(2-)) with beta-cyclodextrins (beta-CD) in aqueous solution are
      determined under both free beta-CD and surface confined beta-CD conditions using
      atomistic simulations. The potential of mean force (PMF) is calculated as a
      function of the environment and the thermodynamic properties of association are
      deduced by integrating the free energy profiles. No inclusion complex between
      SO4(2-) and beta-CD is detected. Nevertheless, the PMF curve obtained for gold
      confined CD seems to evidence a small minimum at a larger separation distance
      that shows specific interactions such as hydrogen bonding outside the cavity. As
      concerns ClO4(-), our simulations reveal the formation of an inclusion complex
      with free beta-CD in perfect agreement with the available experimental results.
      Nevertheless, we do not detect any formation of the host-guest inclusion complex
      under heterogeneous conditions. Finally, the differences observed as a function
      of the anions are interpreted through an atomistic description. The general trend
      of weaker complex stabilities with the increasing free energy of hydration of the
      anions is found in homogeneous systems. 

PMID- 24676344
TI  - Assessment of tumor size as a useful marker for the surgical staging of
      endometrial cancer.
AB  - Accumulating evidence suggests that the estimation of tumor size may improve
      endometrial cancer treatment. We conducted an observational study aimed at
      elucidating the association between tumor size and other universally accepted
      prognostic factors in order to identify suitable preoperative parameters which
      can guide surgery in a subgroup of early corpus endometrial cancer. We found that
      when tumor size increased, both stage and grading were significantly increased.
      Tumor size was correlated with CA 125 serum values, node metastasis and
      peritoneal cytology status. Patients who have grade 1 or 2 endometrioid corpus
      cancer, myometrial invasion < 50% and <= 3 cm largest tumor diameter can only be
      treated with hysterectomy. The tumor largest diameter should be evaluated as a
      preoperative parameter that indicates patients who do not require
      lymphadenectomy.

PMID- 24676345
TI  - Cephalaria transsylvanica-based flower strips as potential food source for bees
      during dry periods in European Mediterranean basin countries.
AB  - The introduction of sown wildflower strips favours the establishment of
      pollinator communities, with special reference to social Apoidea. Here, we
      evaluated the late summer flowering Cephalaria transsylvanica as suitable species
      for strips providing food for pollinators in paucity periods. C. transsylvanica
      showed no particular requirements in terms of seed germination and growth during
      summer. This plant had an excellent potential of self-seeding and competitiveness
      towards weed competitors. C. transsylvanica prevented from entomophilous
      pollination showed inbreeding depression, with a decrease in seed-set and
      accumulation of seed energy reserves. However, C. transsylvanica did not appear
      to be vulnerable in terms of pollination biology since it had a wide range of
      pollinators including bees, hoverflies and Lepidoptera. C. transsylvanica was
      visited mainly by honeybees and bumblebees and these latter pollinators increased
      their visits on C. transsylvanica flowers during early autumn. This plant may be
      useful as an abundant source of pollen during food paucity periods, such as
      autumn. We proposed C. transsylvanica for incorporation into flower strips to be
      planted in non-cropped farmlands in intensively managed agricultural areas as
      well as in proximity of beehives. The latter option may facilitate the honeybees
      collecting pollen and nectar for the colony, thereby ensuring robustness to
      overcome the winter season. 

PMID- 24676347
TI  - Deafness gene expression patterns in the mouse cochlea found by microarray
      analysis.
AB  - BACKGROUND: Tonotopy is one of the most fundamental principles of auditory
      function. While gradients in various morphological and physiological
      characteristics of the cochlea have been reported, little information is
      available on gradient patterns of gene expression. In addition, the audiograms in
      autosomal dominant non syndromic hearing loss can be distinctive, however, the
      mechanism that accounts for that has not been clarified. We thought that it is
      possible that tonotopic gradients of gene expression within the cochlea account
      for the distinct audiograms. METHODOLOGY/PRINCIPAL FINDINGS: We compared
      expression profiles of genes in the cochlea between the apical, middle, and basal
      turns of the mouse cochlea by microarray technology and quantitative RT-PCR. Of
      24,547 genes, 783 annotated genes expressed more than 2-fold. The most remarkable
      finding was a gradient of gene expression changes in four genes (Pou4f3, Slc17a8,
      Tmc1, and Crym) whose mutations cause autosomal dominant deafness. Expression of
      these genes was greater in the apex than in the base. Interestingly, expression
      of the Emilin-2 and Tectb genes, which may have crucial roles in the cochlea, was
      also greater in the apex than in the base. CONCLUSIONS/SIGNIFICANCE: This study
      provides baseline data of gradient gene expression in the cochlea. Especially for
      genes whose mutations cause autosomal dominant non syndromic hearing loss
      (Pou4f3, Slc17a8, Tmc1, and Crym) as well as genes important for cochlear
      function (Emilin-2 and Tectb), gradual expression changes may help to explain the
      various pathological conditions.

PMID- 24676346
TI  - Design and synthesis of a library of lead-like 2,4-bisheterocyclic substituted
      thiophenes as selective Dyrk/Clk inhibitors.
AB  - The Dyrk family of protein kinases is implicated in the pathogenesis of several
      diseases, including cancer and neurodegeneration. Pharmacological inhibitors were
      mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other
      isoforms. Herein, we report the development and optimization of 2,4
      bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The
      optimized hit compounds displayed favorable pharmacokinetic properties and high
      ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger
      selectivity screen, only Clk1 and Clk4 were identified as additional targets of
      compound 48, but no other kinases frequently reported as off-targets.
      Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a
      function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful
      as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B
      with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since
      penetration of the central nervous system (CNS) seems possible based on the
      physicochemical properties, this compound might serve as a lead for the
      development of potential therapeutic agents against glioblastoma. Furthermore, an
      inhibitor selective for Dyrk2 (24) was also identified, which might be are
      suitable as a pharmacological tool to dissect Dyrk2 isoform-mediated functions. 

PMID- 24676348
TI  - Smoking cessation and attempted cessation among adults in the United States.
AB  - AIMS: With growing recognition of stagnant rates of attempted cigarette smoking
      cessation, the current study examined demographic and psychometric
      characteristics associated with successful and attempted smoking cessation in a
      nationally representative sample. This additional understanding may help target
      tobacco cessation treatments toward sub-groups of smokers in order to increase
      attempts to quit smoking. DESIGN, SETTING, AND PARTICIPANTS: Data were used from
      the 2011 U.S. National Health and Wellness Survey (n = 50,000). MEASUREMENTS:
      Current smoking status and demographics, health characteristics, comorbidities,
      and health behaviors. FINDINGS: In 2011, 18%, 29%, and 52% of U.S. adults were
      current, former, or never smokers, respectively. Over one quarter (27%) of
      current smokers were attempting to quit. Current smokers (vs. others) were
      significantly more likely to be poorer, non-Hispanic White, less educated, ages
      45-64, and uninsured, and they had fewer health-conscious behaviors (e.g.,
      influenza vaccination, exercise). Attempting quitters vs. current smokers were
      significantly less likely to be non-Hispanic White and more likely to be younger,
      educated, insured, non-obese, with family history of chronic obstructive
      pulmonary disease, and they had more health-conscious behaviors. CONCLUSIONS:
      Smokers, attempting quitters, and successful quitters differ on characteristics
      that may be useful for targeting and personalizing interventions aiming to
      increase cessation attempts, likelihood, and sustainability.

PMID- 24676349
TI  - Copper-mediated trifluoromethylation of propargyl acetates leading to
      trifluoromethyl-allenes.
AB  - A copper-mediated trifluoromethylation of propargyl acetates with S
      (trifluoromethyl)diphenylsulfonium triflate leading to trifluoromethylated
      allenes in moderate to excellent yields is described. 

PMID- 24676351
TI  - Mediator effect of depressive symptoms on the association between BMI and asthma
      control in adults.
AB  - BACKGROUND: Obesity has been associated with worse asthma control. Depression has
      also been shown to be disproportionally prevalent among patients with asthma and
      among patients with obesity. However, no studies have examined the mediating
      effect of depression on the obesity-asthma relationship. This study examined the
      extent to which depressive symptoms may mediate the obesity-asthma relationship
      in an adult sample. METHODS: A total of 798 patients with physician-diagnosed
      asthma were recruited from the outpatient asthma clinic at Hopital du Sacre-Coeur
      de Montreal. Patients provided demographic and medical history information and
      completed a battery of questionnaires, including the Beck Depression Inventory
      (BDI)-II and the Asthma Control Questionnaire (ACQ). BMI was calculated from self
      reported height and weight. RESULTS: Analyses adjusted for age, sex, years of
      education, cohabitation, and inhaled corticosteroid dose revealed an association
      between BMI and ACQ (beta = 0.017, P = .026), between BMI and BDI-II (beta =
      0.189, P = .002), and between BDI-II and ACQ (beta = 0.044, P < .001). However,
      when both BDI-II and BMI were entered into the same model, BDI-II (beta = 0.044,
      P < .001) but not BMI (beta = 0.009, P = .226) remained significantly associated
      with ACQ. CONCLUSIONS: The results indicate that depression and a high BMI are
      both associated with worse asthma control. However, consistent with our
      hypotheses, the relationship between BMI and worse asthma control was mediated by
      depressive symptoms. Future studies should examine the precise role of depressive
      symptoms in both weight and asthma control.

PMID- 24676352
TI  - Correlation of CTGF gene promoter methylation with CTGF expression in type 2
      diabetes mellitus with or without nephropathy.
AB  - Increasing evidence shows that DNA methylation is involved in the development and
      progression of diabetes mellitus (DM) and its complications. Previous studies
      conducted by our group have indicated that high glucose levels may induce the
      demethylation process of the connective tissue growth factor (CTGF) gene promoter
      and increase the expression of CTGF in human glomerular mesangial cells. Based on
      these findings, the aim of the present study was to investigate the methylation
      level of genomic DNA and the CTGF promoter in patients with type 2 DM and to
      analyze its possible correlation with CTGF expression. Methylation levels of the
      whole genomic DNA were detected by high-performance liquid chromatography in a
      non-diabetes control (NDM) group (n=29), a diabetes without nephropathy (NDN)
      group (n=37) and a diabetes with nephropathy (DN) group (n=38). CTGF promoter
      methylation levels were detected by methylation-specific polymerase chain
      reaction and bisulfite sequencing. The levels of serum CTGF were assessed using
      the enzyme-linked immunosorbent assay. The methylation levels of the whole
      genomic DNA were not significantly different among the three groups. However, the
      CTGF methylation levels in the two diabetes groups were significantly lower than
      those in the NDM group (P<0.05), with the lowest methylation level in the DN
      group (P<0.05). The CTGF protein levels in the DN group were significantly higher
      than those in the NDM and NDN groups (P<0.05). Levels of CTGF were negatively
      correlated with the estimated glomerular filtration rate (eGFR) and the
      methylation level of the promoter, while they were positively correlated with
      age, urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen, creatinine,
      fasting blood sugar and postprandial blood glucose. Multiple stepwise regression
      analysis showed that CTGF expression was associated with the UACR, CTGF
      methylation level and eGFR. DNA methylation is a regulatory mechanism of CTGF
      expression, which is decreased in patients with DM, particularly in those with
      DN, and may contribute to the pathogenesis of nephropathy.

PMID- 24676353
TI  - Retinal morphology of patients with achromatopsia during early childhood:
      implications for gene therapy.
AB  - IMPORTANCE: While older children and adults with achromatopsia have been studied,
      less is known of young children with achromatopsia. OBJECTIVES: To characterize
      the macular and foveal architecture of patients with achromatopsia during early
      childhood with handheld spectral-domain optical coherence tomographic imaging and
      to make phenotype-genotype correlations. DESIGN, SETTING, AND PARTICIPANTS:
      Comparative case series of 9 patients with achromatopsia and 9 age-matched
      control participants at a tertiary ophthalmology referral center. MAIN OUTCOMES
      AND MEASURES: Patients underwent complete ocular examination, full-field
      electroretinography, handheld spectral-domain optical coherence tomographic
      imaging, and screening for genetic mutations. RESULTS: The mean (SD) age of the
      patients with achromatopsia was 4.2 (2.4) years, and the mean (SD) age of the
      control participants was 4.0 (2.1) years. Cone-driven responses to photopic
      single-flash or 30-Hz stimuli were nonrecordable in 7 patients and severely
      attenuated in 2. Rod-driven responses to dim scotopic single-flash stimuli were
      normal in 7 patients and mildly subnormal in 2. Six patients (67%) had foveal
      ellipsoid zone disruption, of which 1 had a hyporeflective zone. Four patients
      (44%) had foveal hypoplasia. The average total retinal thicknesses of the macula
      and fovea in the patients with achromatopsia were 14% and 17% thinner than in the
      control participants (P < .001 and P = .001), which was mostly due to the outer
      retina that was 18% and 26% thinner than in control participants (both P < .001),
      respectively. Genetic testing revealed a common homozygous mutation in CNGB3 in 5
      patients with complete achromatopsia and heterozygous mutations in CNGA3 in 2
      patients with incomplete achromatopsia. The youngest and worst-affected patient
      harbored compound heterozygous mutations in CNGB3 and a single mutation in CNGA3.
      CONCLUSIONS AND RELEVANCE: In early childhood, there is a spectrum of foveal
      pathology that is milder than reported in older individuals with achromatopsia,
      which suggests the need for early therapeutic intervention. Neither age alone nor
      genotype alone predicts the degree of photoreceptor loss or preservation. Thus,
      in anticipation of future gene therapy trials in humans, we propose that handheld
      spectral-domain optical coherence tomography is an important tool for the early
      assessment and stratification of macular architecture in young children with
      achromatopsia.

PMID- 24676350
TI  - Evidence of an overweight/obesity transition among school-aged children and youth
      in Sub-Saharan Africa: a systematic review.
AB  - BACKGROUND: Prevalence of childhood overweight/obesity has increased considerably
      in recent years. The transition to higher rates of overweight/obesity has been
      well documented in high income countries; however, consistent or representative
      data from lower income countries is scarce. It is therefore pertinent to assess
      if rates of overweight/obesity are also increasing in lower income countries, to
      inform public health efforts. OBJECTIVE: This systematic review aimed to
      investigate the evidence for an overweight/obesity transition occurring in school
      aged children and youth in Sub Saharan Africa. METHODS: Studies were identified
      by searching the MEDLINE, Embase, Africa Index Medicus, Global Health, Geobase,
      and EPPI-Centre electronic databases. Studies that used subjective or objective
      metrics to assess body composition in apparently healthy or population-based
      samples of children and youth aged 5 to 17 years were included. RESULTS: A total
      of 283 articles met the inclusion criteria, and of these, 68 were used for
      quantitative synthesis. The four regions (West, Central, East, and South) of Sub
      Saharan Africa were well represented, though only 11 (3.9%) studies were
      nationally representative. Quantitative synthesis revealed a trend towards
      increasing proportions of overweight/obesity over time in school-aged children in
      this region, as well as a persistent problem of underweight. Weighted averages of
      overweight/obesity and obesity for the entire time period captured were 10.6% and
      2.5% respectively. Body composition measures were found to be higher in girls
      than boys, and higher in urban living and higher socioeconomic status children
      compared to rural populations or those of lower socioeconomic status.
      CONCLUSIONS: This review provides evidence for an overweight/obesity transition
      in school-aged children in Sub Saharan Africa. The findings of this review serve
      to describe the region with respect to the growing concern of childhood
      overweight/obesity, highlight research gaps, and inform interventions. PROSPERO
      REGISTRATION NUMBER: CRD42013004399.

PMID- 24676354
TI  - Reference gene selection for gene expression analysis of oocytes collected from
      dairy cattle and buffaloes during winter and summer.
AB  - Oocytes from dairy cattle and buffaloes have severely compromised developmental
      competence during summer. While analysis of gene expression is a powerful
      technique for understanding the factors affecting developmental hindrance in
      oocytes, analysis by real-time reverse transcription PCR (RT-PCR) relies on the
      correct normalization by reference genes showing stable expression. Furthermore,
      several studies have found that genes commonly used as reference standards do not
      behave as expected depending on cell type and experimental design. Hence, it is
      recommended to evaluate expression stability of candidate reference genes for a
      specific experimental condition before employing them as internal controls. In
      acknowledgment of the importance of seasonal effects on oocyte gene expression,
      the aim of this study was to evaluate the stability of expression levels of ten
      well-known reference genes (ACTB, GAPDH, GUSB, HIST1H2AG, HPRT1, PPIA, RPL15,
      SDHA, TBP and YWHAZ) using oocytes collected from different categories of dairy
      cattle and buffaloes during winter and summer. A normalization factor was
      provided for cattle (RPL15, PPIA and GUSB) and buffaloes (YWHAZ, GUSB and GAPDH)
      based on the expression of the three most stable reference genes in each species.
      Normalization of non-reference target genes by these reference genes was shown to
      be considerably different from normalization by less stable reference genes,
      further highlighting the need for careful selection of internal controls.
      Therefore, due to the high variability of reference genes among experimental
      groups, we conclude that data normalized by internal controls can be misleading
      and should be compared to not normalized data or to data normalized by an
      external control in order to better interpret the biological relevance of gene
      expression analysis. 

PMID- 24676356
TI  - Progress in allene chemistry.

PMID- 24676355
TI  - Antagonistic effects of a mixture of low-dose nonylphenol and di-n-butyl
      phthalate (monobutyl phthalate) on the Sertoli cells and serum reproductive
      hormones in prepubertal male rats in vitro and in vivo.
AB  - The estrogenic chemical nonylphenol (NP) and the antiandrogenic agent di-n-butyl
      phthalate (DBP) are regarded as widespread environmental endocrine disruptors
      (EDCs) which at high doses in some species of laboratory animals, such as mice
      and rats, have adverse effects on male reproduction and development. Given the
      ubiquitous coexistence of various classes of EDCs in the environment, their
      combined effects warrant clarification. In this study, we attempted to determine
      the mixture effects of NP and DBP on the testicular Sertoli cells and
      reproductive endocrine hormones in serum in male rats based on quantitative data
      analysis by a mathematical model. In the in vitro experiment, monobutyl phthalate
      (MBP), the active metabolite of DBP, was used instead of DBP. Sertoli cells were
      isolated from 9-day-old Sprague-Dawley rats followed by treatment with NP and
      MBP, singly or combined. Cell viability, apoptosis, necrosis, membrane integrity
      and inhibin-B concentration were tested. In the in vivo experiment, rats were
      gavaged on postnatal days 23-35 with a single or combined NP and DBP treatment.
      Serum reproductive hormone levels were recorded. Next, Bliss Independence model
      was employed to analyze the quantitative data obtained from the in vitro and in
      vivo investigation. Antagonism was identified as the mixture effects of NP and
      DBP (MBP). In this study, we demonstrate the potential of Bliss Independence
      model for the prediction of interactions between estrogenic and antiandrogenic
      agents. 

PMID- 24676357
TI  - Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the
      RNase IIIb domain of DICER1 cause GLOW syndrome.
AB  - BACKGROUND: Constitutional DICER1 mutations have been associated with
      pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig tumours and
      multinodular goitres, while somatic DICER1 mutations have been reported in
      additional tumour types. Here we report a novel syndrome termed GLOW, an acronym
      for its core phenotypic findings, which include Global developmental delay, Lung
      cysts, Overgrowth and Wilms tumour caused by mutations in the RNase IIIb domain
      of DICER1. METHODS AND RESULTS: We performed whole exome sequencing on peripheral
      mononuclear blood cells of an affected proband and identified a de novo missense
      mutation in the RNase IIIb domain of DICER1. We confirmed an additional de novo
      missense mutation in the same domain of an unrelated case by Sanger sequencing.
      These missense mutations in the RNase IIIb domain of DICER1 are suspected to
      affect one of four metal binding sites located within this domain. Pyrosequencing
      was used to determine the relative abundance of mutant alleles in various tissue
      types. The relative mutation abundance is highest in Wilms tumour and unaffected
      kidney samples when compared with blood, confirming that the mutation is mosaic.
      Finally, we performed bioinformatic analysis of microRNAs expressed in murine
      cells carrying specific Dicer1 RNase IIIb domain metal binding site-associated
      mutations. We have identified a subset of 3p microRNAs that are overexpressed
      whose target genes are over-represented in mTOR, MAPK and TGF-beta signalling
      pathways. CONCLUSIONS: We propose that mutations affecting the metal binding
      sites of the DICER1 RNase IIIb domain alter the balance of 3p and 5p microRNAs
      leading to deregulation of these growth signalling pathways, causing a novel
      human overgrowth syndrome.

PMID- 24676358
TI  - IgA measurements in over 12 000 Swedish twins reveal sex differential
      heritability and regulatory locus near CD30L.
AB  - In a broad attempt to improve the understanding of the genetic regulation of
      serum IgA levels, the heritability was estimated in over 12 000 Swedish twins,
      and a genome-wide association study was conducted in a subsample of 9617. Using
      the classical twin model the heritability was found to be significantly larger
      among females (61%) compared with males (21%), while contribution from shared
      environment (20%) was only seen for males. By modeling the genetic relationship
      matrix with IgA levels, we estimate that a substantial proportion (31%) of
      variance in IgA levels can ultimately be explained by the investigated SNPs. The
      genome-wide association study revealed significant association to two loci: (i)
      rs6928791 located on chromosome 6, 22 kb upstream of the gene SAM and SH3 domain
      containing 1 (SASH1) and (ii) rs13300483 on chromosome 9, situated 12 kb
      downstream the CD30 ligand (CD30L) encoding gene. The association to rs13300483
      was replicated in two additional independent Swedish materials. The heritability
      of IgA levels is moderate and can partly be attributable to common variation in
      the CD30L locus. 

PMID- 24676359
TI  - Viral OTU deubiquitinases: a structural and functional comparison.
AB  - Recent studies have revealed that proteases encoded by three very diverse RNA
      virus groups share structural similarity with enzymes of the Ovarian Tumor (OTU)
      superfamily of deubiquitinases (DUBs). The publication of the latest of these
      reports in quick succession prevented proper recognition and discussion of the
      shared features of these viral enzymes. Here we provide a brief structural and
      functional comparison of these virus-encoded OTU DUBs. Interestingly, although
      their shared structural features and substrate specificity tentatively place them
      within the same protease superfamily, they also show interesting differences that
      trigger speculation as to their origins. 

PMID- 24676360
TI  - Expression analysis of serum microRNAs in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology with
      considerable morbidity and mortality. Seeking informative diagnostic markers with
      greater clinical significance is essential for the early diagnosis of IPF.
      microRNAs (miRNAs or miRs) have emerged as novel serum diagnostic biomarkers for
      various diseases. In this study, we performed microarray analysis of the miRNA
      expression profile in the serum of patients with IPF compared to that of control
      subjects. We then performed a preliminary analysis of biological functions for
      the most differentially expressed miRNAs. Some of the microarray results were
      validated by quantitative reverse transcription-polymerase chain reaction (qRT
      PCR). The results from this study provide evidence to link the biological role of
      miRNAs to IPF, and suggest that miRNAs may undertake a variety of functions.
      Additionally, we found that the altered expression levels of miR-21, miR-155 and
      miR-101-3p were associated with forced vital capacity (FVC) and radiological
      features in IPF. Our data may serve as a basis for further investigation,
      preferably in large prospective studies, before miRNA can be used as a non
      invasive screening tool for IPF in routine clinical practice.

PMID- 24676361
TI  - FRZB knockdown upregulates beta-catenin activity and enhances cell aggressiveness
      in gastric cancer.
AB  - Studies have shown that FRZB correlates with gastric tumorigenicity and may play
      role in regulating the Wnt/beta-catenin signaling pathway. In the present study,
      we investigated the correlation between FRZB and the Wnt/beta-catenin signaling
      pathway using gastric cancer tissues and an FRZB-knockdown gastric cancer cell
      line model. The protein levels of FRZB and beta-catenin were examined using
      immunohistochemical staining. FRZB-specific shRNAs were used to generate FRZB
      knockdown MKN45 gastric cancer cells. Cell proliferation assay, suspending
      culture and Annexin V/PI double staining analysis were used to investigate the
      role of FRZB knockdown in cell growth. In vitro migration/invasion assays were
      performed. The expression of Wnt/beta-catenin downstream targets was analyzed by
      RT-PCR. FRZB mRNA levels showed negative correlation with beta-catenin levels in
      paired non-tumor and tumor tissues. FRZB protein levels were negatively
      correlated with beta-catenin levels analyzed by IHC staining. Furthermore, high
      FRZB protein levels were correlated with membrane localization of beta-catenin.
      FRZB knockdown increased gastric cancer cell growth in monolayer and soft agar
      culture; it increased cell aggregates in suspending culture and rendered less
      apoptosis which indicated increased anti-anoikis growth. FRZB knockdown increased
      cell migration and invasion and increased the expression of Wnt/beta-catenin
      downstream targets such as MMP7 and cyclin D1. Our studies revealed that FRZB
      levels were correlated with beta-catenin subcellular localization. Knockdown of
      FRZB in gastric cancer cells increased cell growth and migration/invasion which
      was also accompanied by activation of Wnt/beta-catenin downstream targets. FRZB
      knockdown may upregulate the Wnt/beta-catenin pathway and promote aggressiveness
      in gastric cancer.

PMID- 24676362
TI  - Photochemical ligand ejection from non-sterically promoted Ru(II)bis(diimine)
      4,4'-bi-1,2,3-triazolyl complexes.
AB  - Complexes of the form [Ru(diimine)2(btz)](2+) (btz = 1,1'-dibenzyl-4,4'-bi-1,2,3
      triazolyl) are observed to undergo photochemical ejection of the btz ligand in
      the absence of any promotion through steric congestion to generate cis
      bis(solvent) complexes [Ru(diimine)2(solvent)2](2+). 

PMID- 24676364
TI  - van der Waals trilayers and superlattices: modification of electronic structures
      of MoS2 by intercalation.
AB  - We perform a comprehensive first-principles study of the electronic properties of
      van der Waals (vdW) trilayers via intercalating a two-dimensional (2D) monolayer
      (ML = BN, MoSe2, WS2, or WSe2) between a MoS2 bilayer to form various
      MoS2/ML/MoS2 sandwich trilayers. We find that the BN monolayer is the most
      effective sheet to decouple the interlayer vdW coupling of the MoS2 bilayer, and
      the resulting sandwich trilayer can recover the electronic structures of the MoS2
      monolayer, particularly the direct-gap character. Further study of the MoS2/BN
      superlattices confirms the effectiveness of the BN monolayer for the decoupling
      of the MoS2-MoS2 interaction. In addition, the intercalation of a transition
      metal dichalcogenide (TMDC) MoSe2 or WSe2 sheet makes the sandwich trilayer
      undergo an indirect-gap to direct-gap transition due to the newly formed
      heterogeneous S/Se interfaces. In contrast, the MoS2/WS2/MoS2 sandwich trilayer
      still retains the indirect-gap character of the MoS2 bilayer due to the lack of
      the heterogeneous S/Se interfaces. Moreover, the 3D superlattice of the MoS2/TMDC
      heterostructures also exhibits similar electronic band characters to the
      MoS2/TMDC/MoS2 trilayer heterostructures, albeit a slight decrease of the bandgap
      compared to the trilayers. Compared to the bulk MoS2, the 3D MoS2/TMDC
      superlattice can give rise to new and distinctive properties. Our study offers
      not only new insights into electronic properties of the vdW multilayer
      heterostructures but also guidance in designing new heterostructures to modify
      electronic structures of 2D TMDC crystals. 

PMID- 24676363
TI  - Molecular epidemiology and genetic evolution of the whole genome of G3P[8] human
      rotavirus in Wuhan, China, from 2000 through 2013.
AB  - BACKGROUND: Rotaviruses are a major etiologic agent of gastroenteritis in infants
      and young children worldwide. Since the latter of the 1990s, G3 human rotaviruses
      referred to as "new variant G3" have emerged and spread in China, being a
      dominant genotype until 2010, although their genomic evolution has not yet been
      well investigated. METHODS: The complete genomes of 33 G3P[8] human rotavirus
      strains detected in Wuhan, China, from 2000 through 2013 were analyzed.
      Phylogenetic trees of concatenated sequences of all the RNA segments and
      individual genes were constructed together with published rotavirus sequences.
      RESULTS: Genotypes of 11 gene segments of all the 33 strains were assigned to G3
      P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, belonging to Wa genogroup. Phylogenetic analysis
      of the concatenated full genome sequences indicated that all the modern G3P[8]
      strains were assigned to Cluster 2 containing only one clade of G3P[8] strains in
      the US detected in the 1970s, which was distinct from Cluster 1 comprising most
      of old G3P[8] strains. While main lineages of all the 11 gene segments persisted
      during the study period, different lineages appeared occasionally in RNA segments
      encoding VP1, VP4, VP6, and NSP1-NSP5, exhibiting various allele constellations.
      In contrast, only a single lineage was detected for VP7, VP2, and VP3 genes.
      Remarkable lineage shift was observed for NSP1 gene; lineage A1-2 emerged in 2007
      and became dominant in 2008-2009 epidemic season, while lineage A1-1 persisted
      throughout the study period. CONCLUSION: Chinese G3P[8] rotavirus strains have
      evolved since 2000 by intra-genogroup reassortment with co-circulating strains,
      accumulating more reassorted genes over the years. This is the first large-scale
      whole genome-based study to assess the long-term evolution of common human
      rotaviruses (G3P[8]) in an Asian country.

PMID- 24676365
TI  - The acute effect of flavonoid-rich apples and nitrate-rich spinach on cognitive
      performance and mood in healthy men and women.
AB  - Flavonoids and nitrate in a fruit and vegetable diet may be protective against
      cardiovascular disease and cognitive decline through effects on nitric oxide (NO)
      status. The circulating NO pool is increased via distinct pathways by dietary
      flavonoids and nitrate. Our aim was to investigate the acute effects of apples,
      rich in flavonoids, and spinach, rich in nitrate, independently and in
      combination on NO status, cognitive function and mood in a randomised,
      controlled, cross-over trial with healthy men and women (n = 30). The acute
      effects of four energy-matched treatments (control, apple, spinach and apple +
      spinach) were compared. Endpoints included plasma nitric oxide status (determined
      by measuring S-nitrosothiols + other nitroso species (RXNO)), plasma nitrate and
      nitrite, salivary nitrate and nitrite, urinary nitrate and nitrite as well as
      cognitive function (determined using the Cognitive Drug Research (CDR)
      computerized cognitive assessment battery) and mood. Relative to control, all
      treatments resulted in higher plasma RXNO. A significant increase in plasma
      nitrate and nitrite, salivary nitrate and nitrite as well as urinary nitrate and
      nitrite was observed with spinach and apple + spinach compared to control. No
      significant effect was observed on cognitive function or mood. In conclusion,
      flavonoid-rich apples and nitrate-rich spinach augmented NO status acutely with
      no concomitant improvements or deterioration in cognitive function and mood. 

PMID- 24676367
TI  - Value of coronary artery calcium score to predict severity or complexity of
      coronary artery disease.
AB  - BACKGROUND: Prediction of severity or complexity of coronary artery disease (CAD)
      is valuable owing to increased risk for cardiovascular events. Although the
      association between total coronary artery calcium (CAC) score and severity of
      CAD, Gensini score was not used, it has been previously demonstrated. There is no
      information about the association between total CAC score and complexity of CAD.
      OBJECTIVES: To investigate the association between severity or complexity of
      coronary artery disease (CAD) assessed by Gensini score and SYNTAX score (SS),
      respectively, and coronary artery calcium (CAC) score, which is a noninvasive
      method for CAD evaluation in symptomatic patients with accompanying significant
      CAD. METHODS: Two-hundred-fourteen patients were enrolled. Total CAC score was
      obtained before angiography. Severity and complexity of CAD was assessed by
      Gensini score and SS, respectively. Associations between clinical and
      angiographic parameters and total CAC score were analyzed. RESULTS: Median total
      CAC score was 192 (23.0-729.8), and this was positively correlated with both
      Gensini score (r: 0.299, p<0.001) and SS (r: 0.577, p<0.001). At multivariate
      analysis, it was independently associated with age (beta: 0.154, p: 0.027), male
      gender (beta: 0.126, p: 0.035) and SS (beta: 0.481, p<0.001). Receiver-operating
      characteristic (ROC) curve analysis revealed a cut-off value>809 for SS>32 (high
      SS tertile). CONCLUSION: In symptomatic patients with accompanying significant
      CAD, total CAC score was independently associated with SS and patients with SS>32
      may be detected through high Agatston score.

PMID- 24676366
TI  - I Brazilian position paper on prehypertension, white coat hypertension and masked
      hypertension: diagnosis and management.

PMID- 24676368
TI  - Coronary flow velocity reserve during dobutamine stress echocardiography.
AB  - BACKGROUND: A coronary flow velocity reserve (CFVR)>=2 is adequate to infer a
      favorable prognosis or the absence of significant coronary artery disease.
      OBJECTIVE: To identify parameters which are relevant to obtain CFVR (adequate or
      inadequate) in the left anterior descending coronary artery (LAD) during
      dobutamine stress echocardiography (DSE). METHODS: 100 patients referred for
      detection of myocardial ischemia by DSE were evaluated; they were instructed to
      discontinue the use of beta-blockers 72 hours prior to the test. CFVR was
      calculated as a ratio of the diastolic peak velocity (cm/s) (DPV) on DSE (DPV
      DSE) to baseline DPV at rest (DPV-Rest). In group I, CFVR was <2 and, in group
      II, CFVR was >=2. The Fisher's exact test and Student's t test were used for the
      statistical analyses. P values<0.05 were considered statistically significant.
      RESULTS: At rest, the time (in seconds) to obtain Doppler in LAD in groups I and
      II was not different (53+/-31 vs. 45+/-32; p=0.23). During DSE, LAD was recorded
      in 92 patients. Group I patients were older (65.9+/-9.3 vs. 61.2+/-10.8 years;
      p=0.04), had lower ejection fraction (61+/-10 vs. 66+/-6%; p=0.005), higher DPV
      Rest (36.81+/-08 vs. 25.63+/-06 cm/s; p<0.0001) and lower CFVR (1.67+/-0.24 vs.
      2.53+/-0.57; p<0.0001), but no difference was observed regarding DPVDSE (61.40+/
      16 vs. 64.23+/-16 cm/s; p=0.42). beta-blocker discontinuation was associated with
      a 4-fold higher chance of a CFVR<2 (OR= 4; 95% CI [1.171-13.63], p=0.027).
      CONCLUSION: DPV-Rest was the main parameter to determine an adequate CFVR. beta
      blocker discontinuation was significantly associated with inadequate CFVR. The
      high feasibility and the time to record the LAD corroborate the use of this
      methodology.

PMID- 24676369
TI  - Study of risk factors associated with peripheral arteriopathy in Japanese
      Brazilians from Bauru (SP).
AB  - BACKGROUND: Cardiovascular diseases are the major cause of morbidity and
      mortality in developed and emerging countries. Their main etiology,
      atherosclerosis, is a disseminated disease that affects the coronary, cerebral
      and peripheral territories. The peripheral arterial disease (PAD), as well as its
      consequences, indicates the involvement of the coronary territory. Therefore, its
      better understanding enables proper treatment, delaying local and long-term
      complications, reducing the cost to the health system. OBJECTIVE: This study
      estimates the percentage of PAD in Japanese-Brazilians from Bauru (SP),
      recognized by the high prevalence of metabolic disorders such as hypertension
      (43%), diabetes mellitus (33%) and hypercholesterolemia (60%), and examines the
      association with risk biomarkers. METHODS: This cross-sectional population study
      evaluated 1,330 Japanese-Brazilians of both genders aged>=30 who underwent a
      complete physical examination, anthropometric measurements, laboratory tests and
      ankle-brachial index (ABI). Participants with ABI<=0.90 were diagnosed as having
      PAD. After applying the exclusion criteria, 1,038 individuals were part of the
      analysis. We used Poisson regression to analyze associations with PAD. RESULTS:
      The mean age was 56.8 years and the percentage of PAD was 21.1%, equal among the
      genders. PAD was associated with smoking (PR 2.16 [1.33 to 3.48]) and
      hypertension (PR 1.56 [1.12-2.22]). CONCLUSION: The percentage of PAD in Japanese
      Brazilians was similar to other populations of adverse cardiometabolic profile
      (US PARTNERS and POPADAD). The independent association of PAD with smoking and
      hypertension, but not with other classical risk factors, may depend on the very
      high frequencies of metabolic disorders in this population.

PMID- 24676370
TI  - Time of exercise as indicator of quality control in ergometry services.
AB  - BACKGROUND: The search for quality requires assessment tools in the various
      subdivisions of a health complex. In diagnostic medicine, they are scarce and in
      ergometry suggestions of indicators were not found. OBJECTIVE: To establish
      indicator for quality control on ergometry based on III Guidelines of the
      Brazilian Cardiology Society About Ergometric Test; to verify the percentage of
      tests that have presented the indicator within the compliance in two services of
      the same institution before and after the publication of the document. METHODS: A
      critical analysis of the guidelines in the search for indicator that would
      present: accuracy, reliability, simplicity, validity, sensitivity and ability to
      quantitatively measure the variations in the behavior of quality criteria and
      that would be applicable to all tests. The indicator was applied in tests of 2010
      and 2011 prior to the publication, and after it was adopted by two services of
      the same institution. RESULTS: The indicator that has met the criteria was the
      percentage of ergometric tests with exercise duration between 8 and 12 minutes.
      In the years 2010 and 2011, respectively, the percentage of ergometric tests
      within compliance were 85.5% and 86.1% (p=0.068) at the General Hospital, and
      81.5% and 85.7% (p<0.001) the Service of Periodic Health Assessment. CONCLUSION:
      The exercise time between 8 and 12 minutes can be used as a quality criterion in
      ergometric and services where it was applied, at least 80% of the ergometric
      tests were compliant.

PMID- 24676371
TI  - Influence of term of exposure to high-fat diet-induced obesity on myocardial
      collagen type I and III.
AB  - BACKGROUND: Obesity is a risk factor for many medical complications; medical
      research has shown that hemodynamic, morphological and functional abnormalities
      are correlated with the duration and severity of obesity. OBJECTIVE: Present
      study determined the influence of term of exposure to high-fat diet-induced
      obesity on myocardial collagen type I and III. METHODS: Thirty-day-old male
      Wistar rats were randomly distributed into two groups: a control (C) group fed a
      standard rat chow and an obese (Ob) group alternately fed one of four palatable
      high-fat diets. Each diet was changed daily, and the rats were maintained on
      their respective diets for 15 (C15 and Ob15) and 30 (C30 and Ob30) consecutive
      weeks. Obesity was determined by adiposity index. RESULTS: The Ob15 group was
      similar to the C15 group regarding the expression of myocardial collagen type I;
      however, expression in the Ob30 group was less than C30 group. The time of
      exposure to obesity was associated with a reduction in collagen type I in Ob30
      when compared with Ob15. Obesity did not affect collagen type III expression.
      CONCLUSION: This study showed that the time of exposure to obesity for 30 weeks
      induced by unsaturated high-fat diet caused a reduction in myocardial collagen
      type I expression in the obese rats. However, no effect was seen on myocardial
      collagen type III expression.

PMID- 24676372
TI  - High blood pressure in children and its correlation with three definitions of
      obesity in childhood.
AB  - BACKGROUND: Several authors have correlated the increase of cardiovascular risk
      with the nutritional status, however there are different criteria for the
      classification of overweight and obesity in children. OBJECTIVES: To evaluate the
      performance of three nutritional classification criteria in children, as definers
      of the presence of obesity and predictors of high blood pressure in
      schoolchildren. METHODS: Eight hundred and seventeen children ranging 6 to 13
      years old, enrolled in public schools in the municipality of Vila Velha (ES) were
      submitted to anthropometric evaluation and blood pressure measurement. The
      classification of the nutritional status was established by two international
      criteria (CDC/NCHS 2000 and IOTF 2000) and one Brazilian criterion (Conde e
      Monteiro 2006). RESULTS: The prevalence of overweight was higher when the
      criterion of Conde e Monteiro (27%) was used, and inferior by the IOTF (15%)
      criteria. High blood pressure was observed in 7.3% of children. It was identified
      a strong association between the presence of overweight and the occurrence of
      high blood pressure, regardless of the test used (p<0.001). The test showing the
      highest sensitivity in predicting elevated BP was the Conde e Monteiro (44%),
      while the highest specificity (94%) and greater overall accuracy (63%), was the
      CDC criterion. CONCLUSIONS: The prevalence of overweight in Brazilian children is
      higher when using the classification criterion of Conde e Monteiro, and lower
      when the criterion used is IOTF. The Brazilian classification criterion proved to
      be the most sensitive predictor of high BP risk in this sample.

PMID- 24676373
TI  - Acute effects of continuous positive air way pressure on pulse pressure in
      chronic heart failure.
AB  - BACKGROUND: Patients with heart failure (HF) have left ventricular dysfunction
      and reduced mean arterial pressure (MAP). Increased adrenergic drive causes
      vasoconstriction and vessel resistance maintaining MAP, while increasing
      peripheral vascular resistance and conduit vessel stiffness. Increased pulse
      pressure (PP) reflects a complex interaction of the heart with the arterial and
      venous systems. Increased PP is an important risk marker in patients with chronic
      HF (CHF). Non-invasive ventilation (NIV) has been used for acute decompensated
      HF, to improve congestion and ventilation through both respiratory and
      hemodynamic effects. However, none of these studies have reported the effect of
      NIV on PP. OBJECTIVE: The objective of this study was to determine the acute
      effects of NIV with CPAP on PP in outpatients with CHF. METHODS: Following a
      double-blind, randomized, cross-over, and placebo-controlled protocol, twenty
      three patients with CHF (17 males; 60+/-11 years; BMI 29+/-5 kg/cm2, NYHA class
      II, III) underwent CPAP via nasal mask for 30 min in a recumbent position. Mask
      pressure was 6 cmH2O, whereas placebo was fixed at 0-1 cmH2O. PP and other non
      invasive hemodynamics variables were assessed before, during and after placebo
      and CPAP mode. RESULTS: CPAP decreased resting heart rate (Pre: 72+/-9; vs. Post
      5 min: 67+/-10 bpm; p<0.01) and MAP (CPAP: 87+/-11; vs. control 96+/-11 mmHg;
      p<0.05 post 5 min). CPAP decreased PP (CPAP: 47+/-20 pre to 38+/-19 mmHg post;
      vs. control: 42+/-12 mmHg, pre to 41+/-18 post p<0.05 post 5 min). CONCLUSION:
      NIV with CPAP decreased pulse pressure in patients with stable CHF. Future
      clinical trials should investigate whether this effect is associated with
      improved clinical outcome.

PMID- 24676374
TI  - Hypertrophic response of the association of thyroid hormone and exercise in the
      heart of rats.
AB  - BACKGROUND: Cardiac hypertrophy is a component of cardiac remodeling occurring in
      response to an increase of the activity or functional overload of the heart.
      OBJECTIVE: Assess hypertrophic response of the association of thyroid hormone and
      exercise in the rat heart. METHODS: We used 37 Wistar rats, male, adults were
      randomly divided into four groups: control, hormone (TH), exercise (E), thyroid
      hormone and exercise (H+E); the group received daily hormone levothyroxine sodium
      by gavage at a dose of 20 MUg thyroid hormone/100g body weight, the exercise
      group took swimming five times a week, with additional weight corresponding to
      20% of body weight for six weeks; in group H+E were applied simultaneously TH
      treatment groups and E. The statistics used was analysis of variance, where
      appropriate, by Tukey test and Pearson correlation test. RESULTS: The T4 was
      greater in groups TH and H+E. The total weight of the heart was greater in
      patients who received thyroid hormone and left ventricular weight was greater in
      the TH group. The transverse diameter of cardiomyocytes increased in groups TH, E
      and H+E. The percentage of collagen was greater in groups E and H+E Correlation
      analysis between variables showed distinct responses. CONCLUSION: The association
      of thyroid hormone with high-intensity exercise produced cardiac hypertrophy, and
      generated a standard hypertrophy not directly correlated to the degree of
      fibrosis.

PMID- 24676375
TI  - Quality of life and congenital heart disease in childhood and adolescence.
AB  - Advances in cardiac surgery techniques and early diagnosis have enabled the
      increased survival of individuals with congenital heart disease. The
      investigation of the quality of life in children and adolescents with congenital
      heart disease provides complementary information to clinical data that can assist
      in decision making on the part of health professionals. Although many studies
      have been conducted to investigate the quality of life of children and
      adolescents with congenital heart disease, the results prove to be contradictory;
      while some studies show that congenital heart disease can impact the quality of
      life, others describe a better perception of quality of life among children and
      adolescents who suffer from the disease when compared with healthy control
      subjects. The purpose of this study is to review the literature on the assessment
      of health related quality of life in children and adolescents with congenital
      heart disease, in order to systematize the existing knowledge on this topic
      today. It is observed that research seeks to investigate aspects of personality
      in cardiac patients, their coping strategies used and perceived social support,
      aiming at better understanding the association of these variables with the level
      of quality of life in this population. 

PMID- 24676376
TI  - Chronotropic incompetence in diabetic elderly on echocardiography.

PMID- 24676377
TI  - Trastuzumab cardiotoxicity in patients with breast cancer.

PMID- 24676378
TI  - Case 1/2014--syncope due to cardiogenic shock in a 25-year-old male patient.

PMID- 24676379
TI  - Clinically manifested myocarditis in acute rheumatic fever.

PMID- 24676380
TI  - Detailing the writing of scientific manuscripts: 25-30 paragraphs.

PMID- 24676383
TI  - Multispectral optoacoustic tomography at 64, 128, and 256 channels.
AB  - Optoacoustic (photoacoustic) imaging has already showcased the capacity to offer
      high-resolution small animal visualization in vivo in a variety of cancer,
      cardiovascular, or neuroimaging applications. In particular, multispectral
      optoacoustic tomography (MSOT) has shown imaging along the spectral and the time
      dimensions, enabling sensing of multiple molecules over time and, more recently,
      in real time. Furthermore, cross-sectional imaging of at least 20 mm diameter has
      been showcased in vivo in animals and humans using 64-element curved transducers
      placed along a single curved line. Herein, we investigated the imaging
      improvements gained by utilizing a larger number of detectors and inquired
      whether more detectors will result in measurable image quality improvements. For
      this reason, we implemented MSOT using 64-, 128-, and 256-element transducers and
      imaged the same phantoms and animals under similar conditions. Further,
      corroborated by numerical simulation analysis, our findings quantify the
      improvements in resolution and overall image quality for the increasing number of
      detectors used pointing to significant improvements in image quality for the 256
      detector array, over 64 or 128 detectors.

PMID- 24676384
TI  - Tryptophan as the fingerprint for distinguishing aggressiveness among breast
      cancer cell lines using native fluorescence spectroscopy.
AB  - Tryptophan is investigated as the key native marker in cells to determine the
      level of metastasis competence in breast cell lines using native fluorescence
      spectroscopy. The ratio of fluorescence intensity at 340 nm to intensity at 460
      nm is associated with aggressiveness of the cancer cells. We found that the
      fluorescence of aggressive breast cancer cell has a much higher contribution from
      tryptophan compared with that from the normal cells and nonaggressive breast
      cancer cell.

PMID- 24676381
TI  - A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat
      element DNA methylation longitudinally.
AB  - The low dose radioadaptive response has been shown to be protective against high
      doses of radiation as well as aging-induced genomic instability. We hypothesised
      that a single whole-body exposure of low dose radiation would induce a
      radioadaptive response thereby reducing or abrogating aging-related changes in
      repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation,
      serial peripheral blood sampling was performed and differences in Long
      Interspersed Nucleic Element 1 (L1), B1 and Intracisternal-A-Particle (IAP)
      repeat element methylation between samples were assessed using high resolution
      melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation-
      or aging-related changes in the methylation of peripheral blood, spleen or liver
      L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues
      of cohorts of untreated aging mice showed that the 17-19 month age group
      exhibited higher repeat element methylation than younger or older mice, with no
      overall decline in methylation detected with age. This is the first temporal
      analysis of the effect of low dose radiation on repeat element methylation in
      mouse peripheral blood and the first to examine the long term effect of this dose
      on repeat element methylation in a radiosensitive tissue (spleen) and a tissue
      fundamental to the aging process (liver). Our data indicate that the methylation
      of murine DNA repeat elements can fluctuate with age, but unlike human studies,
      do not demonstrate an overall aging-related decline. Furthermore, our results
      indicate that a low dose of ionising radiation does not induce detectable changes
      to murine repeat element DNA methylation in the tissues and at the time-points
      examined in this study. This radiation dose is relevant to human diagnostic
      radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose
      radiation, does not cause significant short or long term changes to repeat
      element or global DNA methylation. 

PMID- 24676385
TI  - Spectroscopy of discrete vertically oriented single-crystals of n-type
      tetraazaterrylene: understanding the role of defects in molecular semiconductor
      photovoltaics.
AB  - Recent synthetic work has realized a novel (n-type) small-molecule acceptor,
      7,8,15,16-tetra-aza-terrylene (TAT), single-crystals of which can be grown
      oriented along the c-axis crystallographic direction, and over-coated with
      pentacene to form a highly ordered donor/acceptor interface for use in organic
      photovoltaic devices. However, characterization of single TAT crystals reveals
      highly variable emission spectra and excited state dynamics - properties which
      strongly influence photovoltaic performance. Through the use of single-crystal
      widefield imaging, photoluminescence spectroscopy, time correlated single photon
      counting, and resonant Raman studies, we conclude that this variability is a
      result of long-lived low-energy trap-emission from packing defects.
      Interestingly, we also discovered that TAT crystals whose width exceeds ~200 nm
      begin acting as waveguides and optical microcavity resonators for their own
      photoluminescence. Several strategies are proposed for leveraging the size
      dependant optical properties of TAT pillars to further enhance device performance
      using this active layer design. 

PMID- 24676382
TI  - Simultaneous multiplane imaging of human ovarian cancer by volume holographic
      imaging.
AB  - Ovarian cancer is the most deadly gynecologic cancer, a fact which is
      attributable to poor early detection and survival once the disease has reached
      advanced stages. Intraoperative laparoscopic volume holographic imaging has the
      potential to provide simultaneous visualization of surface and subsurface
      structures in ovarian tissues for improved assessment of developing ovarian
      cancer. In this ex vivo ovarian tissue study, we assembled a benchtop volume
      holographic imaging system (VHIS) to characterize the microarchitecture of 78
      normal and 40 abnormal tissue specimens derived from ovarian, fallopian tube,
      uterine, and peritoneal tissues, collected from 26 patients aged 22 to 73
      undergoing bilateral salpingo-oophorectomy, hysterectomy with bilateral salpingo
      oophorectomy, or abdominal cytoreductive surgery. All tissues were successfully
      imaged with the VHIS in both reflectance- and fluorescence-modes revealing
      morphological features which can be used to distinguish between normal, benign
      abnormalities, and cancerous tissues. We present the development and successful
      application of VHIS for imaging human ovarian tissue. Comparison of VHIS images
      with corresponding histopathology allowed for qualitatively distinguishing
      microstructural features unique to the studied tissue type and disease state.
      These results motivate the development of a laparoscopic VHIS for evaluating the
      surface and subsurface morphological alterations in ovarian cancer pathogenesis.

PMID- 24676386
TI  - Current asthma in schoolchildren is related to fungal spores in classrooms.
AB  - BACKGROUND: The presence of visible mold in households is associated with asthma.
      However, the role of "classroom fungus" in the development of childhood asthma,
      as well as the fungal species that may lead to asthma, remains controversial.
      This nationwide school survey was conducted to investigate the correlation
      between fungal spores in classrooms and asthma in schoolchildren. METHODS: From
      April to May 2011, a cross-sectional survey was conducted to assess
      allergic/asthmatic conditions in schoolchildren aged 6 to 15 years old in 44
      schools across Taiwan. Personal histories and current asthmatic conditions were
      collected using a modified International Study of Asthma and Allergies in
      Childhood questionnaire. Fungal spores in classroom were collected using a
      Burkard Personal Air Sampler and counted under light microscopy. Three-level
      hierarchical modeling was used to determine the complex correlation between
      fungal spores in classrooms and childhood asthma. RESULTS: The survey was
      completed by 6,346 out of 7,154 parents (88.7%). The prevalences of physician
      diagnosed asthma, current asthma, and asthma with symptoms reduced on holidays or
      weekends (ASROH) were 11.7%, 7.5%, and 3.1%, respectively. The geometric mean
      spore concentrations of total fungi, Aspergillus/Penicillium, and basidiospores
      were 2,181, 49, and 318 spores/m3. Aspergillus/Penicillium and basidiospores were
      significantly correlated with current asthma and ASROH after adjusting for
      personal and school factors. Of those with current asthma, 41% reported relief of
      symptoms during weekends. CONCLUSIONS: Classroom Aspergillus/Penicillium and
      basidiospores are significantly associated with childhood asthma and ASROH.
      Government health policy should explore environmental interventions for the
      elimination of fungal spores in classrooms to reduce the prevalence of childhood
      asthma.

PMID- 24676387
TI  - Environmental fate of double-stranded RNA in agricultural soils.
AB  - A laboratory soil degradation study was conducted to determine the biodegradation
      potential of a DvSnf7 dsRNA transcript derived from a Monsanto genetically
      modified (GM) maize product that confers resistance to corn rootworm (CRW;
      Diabrotica spp.). This study provides new information to improve the
      environmental assessment of dsRNAs that become pesticidal through an RNAi
      process. Three agricultural soils differing in their physicochemical
      characteristics were obtained from the U.S., Illinois (IL; silt loam), Missouri
      (MO; loamy sand) and North Dakota (ND; clay loam), and exposed to the target
      dsRNA by incorporating insect-protected maize biomass and purified (in vitro
      transcribed) DvSnf7 RNA into soil. The GM and control (non-GM maize) materials
      were added to each soil and incubated at ca. 22  degrees C for 48 hours (h).
      Samples were collected at 12 time intervals during the incubation period,
      extracted, and analyzed using QuantiGene molecular analysis and insect bioassay
      methods. The DT50 (half-life) values for DvSnf7 RNA in IL, MO, and ND soils were
      19, 28, and 15 h based on QuantiGene, and 18, 29, and 14 h based on insect
      bioassay, respectively. Furthermore, the DT90 (time to 90% degradation) values
      for DvSnf7 RNA in all three soils were <35 h. These results indicate that DvSnf7
      RNA was degraded and biological activity was undetectable within approximately 2
      days after application to soil, regardless of texture, pH, clay content and other
      soil differences. Furthermore, soil-incorporated DvSnf7 RNA was non-detectable in
      soil after 48 h, as measured by QuantiGene, at levels ranging more than two
      orders of magnitude (0.3, 1.5, 7.5 and 37.5 ug RNA/g soil). Results from this
      study indicate that the DvSnf7 dsRNA is unlikely to persist or accumulate in the
      environment. Furthermore, the rapid degradation of DvSnf7 dsRNA provides a basis
      to define relevant exposure scenarios for future RNA-based agricultural products.

PMID- 24676388
TI  - Abnormal behaviors and developmental disorder of hippocampus in zinc finger
      protein 521 (ZFP521) mutant mice.
AB  - Zinc finger protein 521 (ZFP521) regulates a number of cellular processes in a
      wide range of tissues, such as osteoblast formation and adipose commitment and
      differentiation. In the field of neurobiology, it is reported to be an essential
      factor for transition of epiblast stem cells into neural progenitors in vitro.
      However, the role of ZFP521 in the brain in vivo still remains elusive. To
      elucidate the role of ZFP521 in the mouse brain, we generated mice lacking exon 4
      of the ZFP521 gene. The birth ratio of our ZFP521Delta/Delta mice was consistent
      with Mendel's laws. Although ZFP521Delta/Delta pups had no apparent defect in the
      body and were indistinguishable from ZFP521+/+ and ZFP521+/Delta littermates at
      the time of birth, ZFP521Delta/Delta mice displayed significant weight reduction
      as they grew, and most of them died before 10 weeks of age. They displayed
      abnormal behavior, such as hyper-locomotion, lower anxiety and impaired learning,
      which correspond to the symptoms of schizophrenia. The border of the granular
      cell layer of the dentate gyrus in the hippocampus of the mice was indistinct and
      granular neurons were reduced in number. Furthermore, Sox1-positive neural
      progenitor cells in the dentate gyrus and cerebellum were significantly reduced
      in number. Taken together, these findings indicate that ZFP521 directly or
      indirectly affects the formation of the neuronal cell layers of the dentate gyrus
      in the hippocampus, and thus ZFP521Delta/Delta mice displayed schizophrenia
      relevant symptoms. ZFP521Delta/Delta mice may be a useful research tool as an
      animal model of schizophrenia. 

PMID- 24676389
TI  - Video surveillance captures student hand hygiene behavior, reactivity to
      observation, and peer influence in Kenyan primary schools.
AB  - BACKGROUND: In-person structured observation is considered the best approach for
      measuring hand hygiene behavior, yet is expensive, time consuming, and may alter
      behavior. Video surveillance could be a useful tool for objectively monitoring
      hand hygiene behavior if validated against current methods. METHODS: Student hand
      cleaning behavior was monitored with video surveillance and in-person structured
      observation, both simultaneously and separately, at four primary schools in urban
      Kenya over a study period of 8 weeks. FINDINGS: Video surveillance and in-person
      observation captured similar rates of hand cleaning (absolute difference <5%, p =
      0.74). Video surveillance documented higher hand cleaning rates (71%) when at
      least one other person was present at the hand cleaning station, compared to when
      a student was alone (48%; rate ratio  = 1.14 [95% CI 1.01-1.28]). Students
      increased hand cleaning rates during simultaneous video and in-person monitoring
      as compared to single-method monitoring, suggesting reactivity to each method of
      monitoring. This trend was documented at schools receiving a handwashing with
      soap intervention, but not at schools receiving a sanitizer intervention.
      CONCLUSION: Video surveillance of hand hygiene behavior yields results comparable
      to in-person observation among schools in a resource-constrained setting. Video
      surveillance also has certain advantages over in-person observation, including
      rapid data processing and the capability to capture new behavioral insights. Peer
      influence can significantly improve student hand cleaning behavior and, when
      possible, should be exploited in the design and implementation of school hand
      hygiene programs.

PMID- 24676390
TI  - Oral bacteria and cancer.

PMID- 24676391
TI  - microRNA-21 protects against ischemia-reperfusion and hypoxia-reperfusion-induced
      cardiocyte apoptosis via the phosphatase and tensin homolog/Akt-dependent
      mechanism.
AB  - Myocardial tissue injury caused by ischemia and hypoxia is a major cause of fatal
      diseases, including coronary atherosclerosis resulting from myocardial infarction
      and stroke. A number of microRNAs have been demonstrated to function as
      protectors against ischemia-reperfusion (I/R) and/or hypoxia-reperfusion (H/R)
      induced myocardial injury, including microRNA-21 (miR-21). However, the
      protective mechanism of miR-21 has not been fully elucidated. The present study
      demonstrated that miR-21 had an anti-apoptotic role in I/R-induced myocardial
      damage in vivo and in H/R-induced H9C2 cell death in vitro. Of note, the present
      study indicates that a common molecular mechanism is likely to exist in I/R- and
      H/R-induced cardiocyte apoptosis. During I/R and H/R, forced expression of miR-21
      upregulated the Akt signaling activity via suppressing the expression of
      phosphatase and tensin homolog (PTEN) and the increased activity of Akt signaling
      further inhibited apoptosis partially by increasing the ratio of B-cell lymphoma
      2(Bcl-2)/Bcl-2-associated X protein, which further suppressed the expression of
      caspase-3. In conclusion, to the best of our knowledge, it was shown for the
      first time that miR-21 had a protective role in I/R- and H/R-induced cardiocyte
      apoptosis via the PTEN/Akt-dependent mechanism. The present study indicates that
      miR-21 may be a promising agent for the treatment of I/R and H/R-induced
      myocardial injury.

PMID- 24676393
TI  - Aberrant DNA methylation in the IFITM1 promoter enhances the metastatic phenotype
      in an intraperitoneal xenograft model of human ovarian cancer.
AB  - A lack of reliable biomarkers for the early detection and risk of metastatic
      recurrences makes ovarian cancer the most lethal gynecological cancer. To
      understand the molecular mechanisms involved in ovarian cancer metastasis in
      vivo, we analyzed the transcriptional expression pattern in metastatic implants
      of human ovarian carcinoma xenografts in mice. The expression of 937 genes was
      significantly different, by at least 2-fold, in the xenografts compared with that
      in SK-OV-3 cells. We investigated the mechanisms that regulate the expression of
      one of the profoundly upregulated genes, interferon-induced transmembrane protein
      1 (IFITM1), in the metastatic implants. Specific CpG sites within the IFITM1
      promoter were hypomethylated in the metastatic implants relative to those in the
      wild-type SK-OV-3 cells. Treating wild-type SK-OV-3 cells with the demethylating
      agent 5-aza-2'-deoxycytidine enhanced IFITM1 expression in a dose-dependent
      manner, implying transcriptional regulation by promoter methylation. We also
      found that IFITM1 overexpression caused increased migration and invasiveness in
      SK-OV-3 cells. Our results demonstrate that IFITM1 could be a novel metastasis
      promoting gene that enhances the metastatic phenotype in ovarian cancer via
      epigenetic transcriptional regulation. Our findings also suggest that the status
      of DNA methylation within the IFITM1 promoter region could be a biomarker
      indicating metastatic progression in ovarian cancer.

PMID- 24676392
TI  - Generation of 3D functional microvascular networks with human mesenchymal stem
      cells in microfluidic systems.
AB  - The generation of functional microvascular networks is critical for the
      development of advanced in vitro models to replicate pathophysiological
      conditions. Mural cells provide structural support to blood vessels and secrete
      biomolecules contributing to vessel stability and functionality. We investigated
      the role played by two endothelium-related molecules, angiopoietin (Ang-1) and
      transforming growth factor (TGF-beta1), on bone marrow-derived human mesenchymal
      stem cell (BM-hMSC) phenotypic transition toward a mural cell lineage, both in
      monoculture and in direct contact with human endothelial cells (ECs), within 3D
      fibrin gels in microfluidic devices. We demonstrated that the effect of these
      molecules is dependent on direct heterotypic cell-cell contact. Moreover, we
      found a significant increase in the amount of alpha-smooth muscle actin in
      microvascular networks with added VEGF and TGF-beta1 or VEGF and Ang-1 compared
      to networks with added VEGF alone. However, the addition of TGF-beta1 generated a
      non-interconnected microvasculature, while Ang-1 promoted functional networks,
      confirmed by microsphere perfusion and permeability measurements. The presence of
      mural cell-like BM-hMSCs coupled with the addition of Ang-1 increased the number
      of network branches and reduced mean vessel diameter compared to EC only
      vasculature. This system has promising applications in the development of
      advanced in vitro models to study complex biological phenomena involving
      functional and perfusable microvascular networks. 

PMID- 24676394
TI  - Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in
      SGC-7901 gastric cancer cells.
AB  - Gastric cancer, one of the most common malignancies worldwide, typically has a
      poor prognosis and poor survival rate. Previous studies have investigated the
      chemopreventive effect of celecoxib. In the present study, the SGC-7901 human
      gastric cancer cell line was utilized to examine the chemopreventive mechanisms
      of celecoxib. The inhibition of cell proliferation was determined using MTT
      assay, cell apoptosis was monitored by terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL) and flow cytometry, and cell
      ultrastructural changes were assessed via transmission electron microscopy. The
      mRNA expression of Akt, caspase-8 and -9 was examined using quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR) and p-Akt, procaspase-8 and -9
      were analyzed via western blotting. The results showed that celecoxib inhibited
      the proliferation of SGC-7901 cells in a time- and dose-dependent manner.
      Additionally, celecoxib induced apoptosis as substantiated by typical apoptotic
      bodies, autophagosomes and an increased apoptotic rate. It was found that
      following celecoxib treatment, Akt mRNA expression was not significantly altered,
      and that p-Akt protein levels decreased in a time- and dose-dependent manner.
      Additionally, caspase-8 and -9 mRNA expression was significantly increased, while
      procaspase-8 and -9 protein expression decreased relative to the time- and dose
      dependent effects. These results demonstrated that celecoxib induced apoptosis
      and autophagy of gastric cancer cells in vitro through the PI3K/Akt signaling
      pathway. Moreover, our findings suggested that celecoxib induces apoptosis in
      gastric cancer cells through the mitochondrial and death receptor pathways,
      providing additional understanding regarding the chemopreventive behaviors of
      celecoxib and its uses in cancer therapy.

PMID- 24676395
TI  - Induced phagocytic particle uptake into a giant unilamellar vesicle.
AB  - Phagocytosis, the uptake and ingestion of solid particles into living cells, is a
      central mechanism of our immune system. Due to the complexity of the uptake
      mechanism, the different forces involved in this process are only partly
      understood. Therefore the usage of a giant unilamellar vesicle (GUV) as the
      simplest biomimetic model for a cell allows one to investigate the influence of
      the lipid membrane on the energetics of the uptake process. Here, a photonic
      force microscope (PFM) is used to approach an optically trapped 1 MUm latex bead
      to an immobilized GUV to finally insert the particle into the GUV. By analysing
      the mean displacement and the position fluctuations of the trapped particle
      during the uptake process in 3D with nanometre precision, we are able to record
      force and energy profiles, as well as changes in the viscous drag and the
      stiffness. After observing a global followed by a local deformation of the GUV,
      we measured uptake energies of 2000 kT to 5500 kT and uptake forces of 4 pN to 16
      pN for Egg-PC GUVs with sizes of 18-26 MUm and varying membrane tension. The
      measured energy profiles, which are compared to a Helfrich energy model for local
      and global deformation, show good coincidence with the theoretical results. Our
      proof-of-principle study opens the door to a large number of similar experiments
      with GUVs containing more biochemical components and complexity. This bottom-up
      strategy should allow for a better understanding of the physics of phagocytosis. 

PMID- 24676396
TI  - Optical three dimensional coherent spectroscopy.
AB  - Optical multdimensional coherent spectroscopy has recently been the subject of
      significant activity. While two-dimensional spectroscopy is most common, it is
      possible to extend the method into three dimensions. This perspective reviews the
      different approaches to three-dimensional spectroscopy and the systems that have
      been studied with it. The advantages of adding an additional dimension are
      discussed and compared to the resulting experimental challenges. 

PMID- 24676400
TI  - Preparation of layered double hydroxide/chlorophyll a hybrid nano-antennae: a key
      step.
AB  - In the first step to obtain an efficient nano-antenna in a bottom-up approach,
      new hybrid materials were synthesized using a set of layered double hydroxides
      (LDHs) with basic properties and pure chlorophyll a (Chl a). The stability of the
      adsorbed monolayer of Chl a was shown to be dependent on the nature and the ratio
      of the different metal ions present in the LDHs tested. The hybrid materials
      turned out to be adequate for stabilizing Chl a on Mg/Al LDHs for more than a
      month under ambient conditions while a limited catalytic decomposition was
      observed for the Ni/Al LDHs leading to the formation of pheophytin. These changes
      were followed by namely XRD, DR-UV-vis and fluorescence spectroscopies of the
      hybrid antennae and of the solutions obtained from their lixiviation with acetone
      or diethylether. On Mg/Al hydrotalcites the stability of the adsorbed Chl a was
      equivalent for values of the metal atom ratio ranging from 2 to 4. The latter
      hybrids should constitute a good basis to form efficient nanoscale light
      harvesting units following intercalation of selected dyes. This work describes an
      efficient preparation of Chl a that allows scale-up as well as the obtention of a
      stable Chl a monolayer on the surface of various LDHs. 

PMID- 24676401
TI  - Prevalence and associations of VTE in patients with newly diagnosed lung cancer.
AB  - BACKGROUND: The risk of VTE before anticancer therapy in patients with lung
      cancer is not well defined. METHODS: A total of 673 hospitalized patients with
      newly diagnosed lung cancer were examined for VTE within 1 week after admission
      at five hospitals between January 2009 and January 2011. Additionally, VTE
      diagnoses within the last 3 months were reviewed. All VTE events were confirmed
      with imaging studies. Blood cell count and serum carcinoembryonic antigen (CEA)
      levels were measured before initial treatment. RESULTS: VTE events occurred in 89
      of the 673 patients (13.2%) enrolled in this study. Forty-two patients (6.2%)
      developed lower extremity DVT alone, 33 patients (4.9%) developed pulmonary
      embolism (PE) alone, and 14 patients (2.1%) developed both DVT and PE. By
      multivariate logistic regression analysis, distant metastasis (OR, 2.2; 95% CI,
      1.2-3.9) and leukocytosis (OR, 2.8; 95% CI, 1.5-5.4) were significantly
      associated with DVT, adenocarcinoma (OR, 2.1; 95% CI, 1.1-4.4) and anemia (OR,
      4.6; 95% CI, 1.4-14.5) were significantly associated with PE, and an elevated CEA
      level in tertiles was linearly associated with PE (P for trend = .06). The area
      under the receiver operating characteristic curve for the prognostic or
      diagnostic CEA values was 0.68 (95% CI, 0.59-0.76; P < .001). CONCLUSIONS: The
      prevalence of VTE was high in patients with newly diagnosed lung cancer. In
      patients with lung cancer, the factors associated with DVT might be different
      from those associated with PE. An elevated CEA level might facilitate the
      identification of patients at a higher risk of developing PE.

PMID- 24676402
TI  - Beyond sperm cells: a qualitative study on constructed meanings of the sperm
      donor in lesbian families.
AB  - STUDY QUESTION: What meanings do lesbian couples construct regarding their sperm
      donor? SUMMARY ANSWER: For some parents, the donor was increasingly presented as
      a person, whereas for other parents, the donor was seen as an instrument from the
      moment they received the sperm donation. WHAT IS KNOWN ALREADY: Few studies
      specifically focus on how lesbian couples deal with the issue of third-party
      anonymous gamete donation. It is often assumed that they have fewer difficulties
      than heterosexual couples with the involvement of a male procreator, since their
      status as a donor conception family is 'socially visible' and there is no social
      father who fears exclusion. STUDY DESIGN, SIZE, DURATION: Semi-structured
      interviews were conducted with 10 lesbian couples (20 participants), recruited
      via the Ghent University Hospital. All couples had at least one child, conceived
      through anonymous donor insemination, between 7 and 10 years old.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Within the data corpus, a particular
      data set was analyzed where couples referred to their donor and his position in
      their family. Step-by-step inductive thematic analysis was performed resulting in
      themes that are grounded in the data. All phases of the analysis were followed by
      team discussion. MAIN RESULTS AND THE ROLE OF CHANCE: This study reveals
      different donor constructs, indicating different ways of dealing with the third
      party involvement in the family. Some parents diminish the role of the donor
      throughout family life and continue to present him as an instrument: something
      they needed in order to become parents. Others show an increasing interest in the
      donor as the children mature, which results in a more personalized account of the
      donor. LIMITATIONS, REASONS FOR CAUTION: In our qualitative cross-sectional
      study, we collected retrospectively constructed stories. Longitudinal qualitative
      and quantitative research is required to allow for an extrapolation of the
      conclusions made. WIDER IMPLICATIONS OF THE FINDINGS: This study shows how the
      concept of the donor is constructed within lesbian families and how it is
      challenged by the child's developing personality and features. When counseling
      prospective parents, it could therefore be useful to discuss the concept of the
      anonymous donor beyond the conception phase. STUDY FUNDING/COMPETING INTEREST(S):
      The project was funded by the Research Fund of Ghent University, Belgium. There
      are no competing interests.

PMID- 24676403
TI  - Too old to have children? Lessons from natural fertility populations.
AB  - STUDY QUESTION: Is it possible to construct an age curve denoting the ages above
      which women are biologically too old to reproduce? SUMMARY ANSWER: We constructed
      a curve based on the distribution of female age at last birth in natural
      fertility populations reflecting the ages above which women have become
      biologically too old to have children. WHAT IS KNOWN ALREADY: The median age at
      last birth (ALB) for females is ~40-41 years of age across a range of natural
      fertility populations. This suggests that there is a fairly universal pattern of
      age-related fertility decline. However, little is known about the distribution of
      female ALB and in the present era of modern birth control, it is impossible to
      assess the age-specific distribution of ALB. Reliable information is lacking that
      could benefit couples who envisage delaying childbearing. STUDY DESIGN, SIZE,
      DURATION: This study is a review of high-quality historical data sets of natural
      fertility populations in which the distributions of female age at last birth were
      analysed. The studies selected used a retrospective cohort design where women
      were followed as they age through their reproductive years.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Using a common set of eligibility
      criteria, large data files of natural fertility populations were prepared such
      that the analysis could be performed in parallel across all populations. Data on
      the ALB and confounding variables are presented as box and whisker plots denoting
      the 5th, 25th, 50th, 75th and 95th percentile distribution of the age at last
      birth for each population. The analysis includes the estimation of Kaplan-Meier
      curves for age at last birth of each population. The hazard curve for ALB was
      obtained by plotting the smoothed hazard curve of each population and taking the
      lowest hazard within a time period of at least 5 years. This lowest hazard curve
      was then transformed into a cumulative distribution function representing the
      composite curve of the end of biological fertility. This curve was based on the
      data from three of the six populations, having the lowest hazards of end of
      fertility. MAIN RESULTS AND THE ROLE OF CHANCE: We selected six natural fertility
      populations comprising 58 051 eligible women. While these populations represent
      different historical time periods, the distribution of the ages at last birth is
      remarkably similar. The curve denoting the end of fertility indicates that <3% of
      women had their last birth at age 20 years meaning that almost 98% were able to
      have at least one child thereafter. The cumulative curve for the end of fertility
      slowly increases from 4.5% at age 25 years, 7% at age 30 years, 12% at age 35
      years and 20% at age 38 years. Thereafter, it rises rapidly to about 50% at age
      41, almost 90% at age 45 years and approaching 100% at age 50 years. LIMITATIONS,
      REASONS FOR CAUTION: It may be argued that these historical fertility data do not
      apply to the present time; however, the age-dependent decline in fertility is
      similar to current populations and is consistent with the pattern seen in women
      treated by donor insemination. Furthermore, for reproductive ageing, we note that
      it is unlikely that such a conserved biological process with a high degree of
      heritability would have changed significantly within a century or two. WIDER
      IMPLICATIONS OF THE FINDINGS: We argue that the age-specific ALB curve can be
      used to counsel couples who envisage having children in the future. Our findings
      challenge the unsubstantiated pessimism regarding the possibility of natural
      conception after age 35 years. STUDY FUNDING/COMPETING INTEREST(S): No external
      funding was either sought or obtained for this study. There are no conflicts of
      interest to be declared.

PMID- 24676404
TI  - Alterations in HIV-1 gp120 V3 region are necessary but not sufficient for
      coreceptor switching in CRF07_BC in China.
AB  - The most predominant HIV-1 strains in China's current epidemic is the Circulating
      Recombinant Form 07_BC (CRF07_BC). CRF07_BC is mainly considered as a CCR5-tropic
      (R5) virus, since CXCR4-tropic (X4) viruses have thus far not been found in this
      subtype, and the molecular determinants of coreceptor switching remain unknown.
      To investigate the mechanisms underlying coreceptor requirement in CRF07_BC
      viruses, we characterized a panel of pNL4-3-based chimeric viruses with mutated
      V3 loop regions derived from an HIV-1 CRF07_BC infectious clone pXJDC13. Among 17
      chimeric viruses, seven were dual-tropic and induced syncytium formation in MT-2
      cells. Two amino acid insertions between positions 13 and 14, as well as arginine
      substitution at position 11 or 16 (IG insertion and P16R mutation or MG insertion
      and S11R mutation), conferred the chimeric viruses CXCR4-tropic features, which
      were same as subtype C X4 viruses. Next, to construct CRF07_BC X4 variants,
      mutated V3 loops were cloned into the CRF07_BC infectious clone pXJDC13. These V3
      loops, which in the pNL4-3 backbone conferred chimeric viruses with CXCR4-using
      ability, abrogated infectivity completely in the CRF07_BC pXJDC13 genetic
      background. Similarly, IG insertion or MG insertion and S11R mutation
      dramatically diminished or completely abolished viral infectivity in other
      envelopes of subtype C or CRF07_BC. These results suggest that the effects of IG
      insertion and P16R mutation or MG insertion and S11R mutation on CXCR4 usage are
      context dependent, and additional mutations elsewhere in the envelope are needed
      to compensate for these fitness-reducing alterations. 

PMID- 24676405
TI  - Screening of hepatocyte proteins binding with the middle surface protein of the
      hepatitis B virus by the yeast two-hybrid system.
AB  - The effect of the middle hepatitis B virus surface protein (MHBs) remains to be
      elucidated. To investigate the biological function of the MHBs protein, the
      present study performed yeast two-hybrid screening to search for proteins that
      interact with the MHBs protein in hepatocytes. The bait plasmid expressing the
      MHBs protein was constructed by cloning the gene of the MHBs protein into pGBKT7,
      then the recombinant plasmid DNA was transformed into AH109 yeast (a type). The
      transformed yeast AH109 was mated with yeast Y187 (alpha type) containing the
      liver cDNA library plasmid in 2X yeast peptone dextrose adenine (YPDA) medium.
      The mated diploid yeast was plated on quadruple dropout medium (SD/-Trp-Leu-His
      Ade) containing X-alpha-gal for selection and screening. Following extracting and
      sequencing of the plasmids from positive (blue) colonies, the sequence analysis
      was conducted and analyzed by bioinformatics methods. Two colonies were selected
      and sequenced. Among them, one was the human DNA sequence from the clone RP11
      490D19 on chromosome 9 and the other was homo sapiens 12 BAC RP11-180M15 (Roswell
      Park Cancer Institute Human BAC Library). The yeast two-hybrid system is an
      effective method for identifying hepatocyte proteins that interact with MHBs. The
      MHBs protein binds with different proteins suggesting that it has multiple
      functions in vivo.

PMID- 24676406
TI  - The expression of p66shc in peripheral blood monocytes is increased in patients
      with coronary heart disease and correlated with endothelium-dependent
      vasodilatation.
AB  - The objective of this study is to detect the p66shc mRNA and protein expression
      of the peripheral blood monocytes (PBMs) in coronary heart disease patients (CHD)
      and controls, to evaluate the correlation between the expression of p66shc mRNA
      in the PBMs and endothelium-dependent vasodilatation. This study included 78
      coronary angiography-documented CHD patients (CHD group) and 38 non-CHD controls
      (control group). The p66shc mRNA and protein levels were determined by
      quantitative real-time PCR and western blotting. The flow-mediated dilatation
      (FMD, endothelium-dependent), nitroglycerine-induced dilatation (NID, endothelium
      independent) and carotid intimal medial thickness (CIMT) were detected using high
      resolution ultrasound. The p66shc mRNA and the protein expression levels in the
      PBMs were significantly higher in the CHD group compared with the control group
      (p = 0.007 and 0.001). The FMD (p < 0.001) and NID (p = 0.013) were significantly
      lower and the CIMT (p = 0.007) was significantly thicker in the CHD patients than
      in the controls. In the univariate analysis, the expression of the p66shc mRNA in
      the PBMs was significantly positively correlated with the serum LDL-C and
      homocysteine levels and the CIMT and was inversely correlated with the FMD and
      the NID (all p < 0.001). In the multiple linear regression analysis, the FMD (p <
      0.001), LDL-C (p = 0.002) and homocysteine levels (p = 0.002) remained
      independently correlated with the p66shc mRNA expression. These findings
      highlight a pivotal role for the expression of p66shc in CHD and endothelial
      dysfunction, which might represent a molecular target to prevent endothelial
      dysfunction-related disease. 

PMID- 24676407
TI  - Late aneurysm formation of Valsalva sinus after aortic valve replacement due to
      Takayasu's arteritis.
AB  - Takayasu's arteritis (TA) is an inflammatory disease of unknown etiology
      involving the aorta and its branches, and also causes aortic regurgitation (AR).
      One of the most serious but rare complications after aortic valve replacement
      (AVR) in TA is aneurysm formation of the sinus of Valsalva. A 64-year-old woman
      had undergone AVR with a prosthetic valve for AR due to TA 4 years earlier and
      had received an implanted permanent pacemaker for complete atrioventricular block
      (AVB) 2 years later. Aortography 4 years postoperatively demonstrated aneurysm
      formation (47 mm in diameter) at the sinus of Valsalva although preoperative
      aortography showed severe AR without dilatation of the sinus of Valsalva. We
      recommended reoperation for the aneurysm but the patient refused. The
      perioperative histopathological examination revealed extensive destruction of the
      medial elastic fibers. Both the fragility of the sinus of Valsalva and the
      residual inflammation could have caused the patient's aneurysm formation.
      Moreover, extension of TA into the ventricular septum or mechanical compression
      of the aneurysm against the conduction system might have caused her progressive
      AVB. Close and lifelong follow-up for patients with TA regarding development of
      aneurysm after surgical treatment is indispensable when fragility of the aortic
      root had been confirmed. 

PMID- 24676408
TI  - Differentiation and molecular profiling of human embryonic stem cell-derived
      corneal epithelial cells.
AB  - It has been suggested that the isolation of scalable populations of limbal stem
      cells may lead to radical changes in ocular therapy. In particular, the
      derivation and transplantation of corneal stem cells from these populations may
      result in therapies providing clinical normality of the diseased or damaged
      cornea. Although feasible in theory, the lack of donor material in sufficient
      quantity and quality currently limits such a strategy. A potential scalable
      source of corneal cells could be derived from pluripotent stem cells (PSCs). We
      developed an in vitro and serum-free corneal differentiation model which displays
      significant promise. Our stepwise differentiation model was designed with
      reference to development and gave rise to cells which displayed similarities to
      epithelial progenitor cells which can be specified to cells displaying a corneal
      epithelial phenotype. We believe our approach is novel, provides a robust model
      of human development and in the future, may facilitate the generation of corneal
      epithelial cells that are suitable for clinical use. Additionally, we demonstrate
      that following continued cell culture, stem cell-derived corneal epithelial cells
      undergo transdifferentiation and exhibit squamous metaplasia and therefore, also
      offer an in vitro model of disease.

PMID- 24676410
TI  - Network meta-analyses of antiepileptic drug efficacy and tolerability in drug
      resistant focal epilepsies: a clinical perspective.
AB  - PURPOSE: Network meta-analysis (NMA) is a new technique that allows multiple
      treatment comparisons and provides estimates of effect sizes for all possible
      pair-wise comparisons. Several NMAs of antiepileptic drug (AED) efficacy and
      tolerability in individuals with refractory focal epilepsy, however, came to non
      specific and, in some cases, divergent conclusions. We review some clinical
      factors that may be responsible for these inconsistent findings. RESULTS: A major
      issue is the small number of individuals included in the meta-analyses with
      consequent wide confidence intervals and lack of ability to achieve significant
      results. Further issues are lack of robustness of the measured efficacy outcome
      the responder ratio (the percentage of individuals with a >50 % improvement in
      seizure frequency); the selection of randomized studies (RCTs) included, i.e.,
      the inclusion of studies with heterogeneous populations (children and adults);
      and inclusion of people treated with different doses of the experimental drug.
      Some methods of analysing data from RCTs, such as the last observation carried
      forward (LOCF) analysis, the choice of different phases of the study to compare
      to baseline, and the year in which the trial was conducted, selectively affect
      measurement of efficacy outcomes. Titration speed and other methodological
      aspects selectively affect tolerability. CONCLUSION: Several factors restrict the
      analysis of clinically useful estimates of the comparative efficacy of AEDs,
      while analysis of tolerability may be easier to accomplish.

PMID- 24676411
TI  - Applications of fat grafting in facial aesthetic skeletal surgery.
AB  - BACKGROUND: Aesthetic skeletal surgery of the face is a powerful tool to alter
      the facial skeleton; the facial form is enhanced through the use of alloplastic
      implants and osteotomies of the facial bones. However, the ultimate aesthetic
      appearance is dictated by how the soft tissue envelope drapes over the altered
      skeletal foundation. Intraoperative and postoperative fat grafting enhances the
      final aesthetic result in patients who undergo skeletal aesthetic procedures.
      OBJECTIVES: The authors describe cases in which selective fat grafting has been
      successful in optimizing facial soft tissue symmetry in patients undergoing
      skeletal aesthetic surgery of the face. METHODS: A retrospective chart review of
      all patients who underwent aesthetic skeletal surgery of the face between
      November 1, 2003, and October 31, 2011, in the Department of Surgery at
      Georgetown University Hospital was performed, and any patient who required fat
      grafting either at the time of aesthetic facial skeletal surgery or in the
      postoperative period was identified (n = 21). Common indications for fat grafting
      and the surgical plans are reviewed and presented in this article. RESULTS:
      Twenty-one patients were identified who required 37 fat grafting procedures
      either at the time of aesthetic skeletal surgery of the face or in the
      postoperative period. The procedures most frequently requiring fat grafting were
      genioplasty, facial shape modifications, and facial symmetry improvement. Fat
      grafting most commonly corrected irregularities or asymmetries and improved the
      soft tissue contour overlying repositioned bone or alloplastic implants. Most
      patients were female (72%) with a mean age of 42 years (range, 4-58 years). There
      were 4 complications in total: 3 surgical site infections (managed conservatively
      in 1 patient and with incision and drainage in the remaining 2) and 1 hematoma
      requiring drainage and closure on the day of surgery. CONCLUSIONS: Knowledge of
      which procedures are likely to require fat grafting and the techniques for doing
      so can improve the plastic surgeon's ability to provide optimal aesthetic results
      following facial skeletal alterations.

PMID- 24676409
TI  - The relevance of testing the efficacy of anti-angiogenesis treatments on cells
      derived from primary tumors: a new method for the personalized treatment of renal
      cell carcinoma.
AB  - Despite the numerous available drugs, the most appropriate treatments for
      patients affected by common or rare renal cell carcinomas (RCC), like those
      associated with the Xp11.2 translocation/transcription factor for immunoglobulin
      heavy-chain enhancer 3 (TFE3) gene fusion (TFE3 RCC), are not clearly defined. We
      aimed to make a parallel between the sensitivity to targeted therapies on living
      patients and on cells derived from the initial tumor. Three patients diagnosed
      with a metastatic RCC (one clear cell RCC [ccRCC], two TFE3 RCC) were treated
      with anti-angiogenesis drugs. The concentrations of the different drugs giving
      50% inhibition of cell proliferation (IC50) were determined with the Thiazolyl
      Blue Tetrazolium Bromide (MTT) assay on cells from the primary tumors and a
      reference sensitive RCC cell line (786-O). We considered the cells to be
      sensitive if the IC50 was lower or equal to that in 786-O cells, and insensitive
      if the IC50 was higher to that in 786-O cells (IC 50 of 6 +/- 1 uM for sunitinib,
      10 +/- 1 uM for everolimus and 6 +/- 1 uM for sorafenib). Based on this standard,
      the response in patients and in cells was equivalent. The efficacy of anti
      angiogenesis therapies was also tested in cells obtained from five patients with
      non-metastatic ccRCC, and untreated as recommended by clinical practice in order
      to determine the best treatment in case of progression toward a metastatic grade.
      In vitro experiments may represent a method for evaluating the best first-line
      treatment for personalized management of ccRCC during the period following
      surgery.

PMID- 24676412
TI  - Commentary on: A population-level analysis of bilateral breast reduction: does
      age affect early complications?

PMID- 24676413
TI  - OnabotulinumtoxinA for the treatment of a "gummy smile".
AB  - BACKGROUND: Excessive gingival display, or a "gummy smile," is defined as 2 mm or
      more of gingival exposure upon smiling. Such excessive gingival exposure can be
      aesthetically unappealing to patients. One factor that contributes to a gummy
      smile is hyperfunctional lip elevator muscles. OBJECTIVES: The authors evaluate
      onabotulinumtoxinA as a safe and minimally invasive treatment for a gummy smile.
      METHODS: In this prospective study, 14 patients (13 women, 1 man) underwent
      pretreatment photographs and measurements, followed by bilateral injection of
      onabotulinumtoxinA into their lip elevator muscles. All patients selected for the
      study had more than 2mm of gingival show and were classified as having a "cuspid
      smile," where action of all elevator muscles raised the upper lip- like a window
      shade-to expose the upper teeth and gingival scaffold; these patients were
      thought to have a better chance for a more superior result. Repeat measurements
      and photographs were collected at 2 weeks and 3 months. Patient-reported outcomes
      were collected at 2 weeks, and data were compared to determine the correlative
      relationship. RESULTS: An average of 5 units (range, 4-6 U) of onabotulinumtoxinA
      were injected into 3 sites bilaterally. The average preinjection gingival show
      over the central incisors and canines were 4.89 mm and 4.25 mm, respectively.
      Postinjection gingival show decreased to an average of 0.75 mm (85% improvement)
      and 0.74 mm (83% improvement) over the central incisors and canines,
      respectively. Average follow-up time was 12.6 days. One patient felt the
      resulting smile was unattractive and opted not to undergo repeat injections,
      while all other study participants experienced no negative effects and wished to
      undergo repeat treatment. CONCLUSIONS: As treatment for a "gummy smile,"
      onabotulinumtoxinA provides an effective, minimally invasive, and safe therapy.
      This treatment option can lead to significant improvement in smile aesthetics
      with high patient satisfaction. LEVEL OF EVIDENCE: 3.

PMID- 24676414
TI  - Autologous fat processing via the Revolve system: quality and quantity of fat
      retention evaluated in an animal model.
AB  - BACKGROUND: Currently, fat graft viability and retention cannot be reliably
      predicted. The reasons for this variability are not fully understood, although
      fat processing has been implicated. OBJECTIVES: The authors compare the in vitro
      quantity and in vivo fat retention from lipoaspirate processed by the Revolve
      system (LifeCell, Bridgewater, New Jersey) compared with centrifugation and
      decantation. METHODS: Ten patients were enrolled in this prospective study.
      Lipoaspirate from each patient was processed by each of 3 methods: decantation,
      centrifugation, and the Revolve system. Biochemical characteristics and free oil,
      adipose, and aqueous phases of the processed fats were determined. Fat grafts
      were implanted in nude mice; volume retention and quality of the fat grafts were
      evaluated after 28 days. Viability of retained fat was demonstrated by intact
      adipocytes and neovascularization on histology. RESULTS: Of the 10 patients, 9
      were women and 1 was a man. Mean patient age was 40.7 +/- 8.9 years (range, 30-55
      years). Fat tissue obtained from all methods had good physiological properties
      with neutral pH and isotonic salt concentrations. The Revolve system yielded
      significantly less blood cell debris, a higher percentage of adipose tissue, and
      a lower percentage of free oil compared with the other 2 methods. Fat tissue
      retention from Revolve samples was significantly higher (73.2%) than that from
      decanted samples (37.5%) and similar to that from centrifuged samples (67.7%).
      CONCLUSIONS: The Revolve system produced physiologically compatible, preinjection
      fat with reduced contaminants and free oil in conjunction with high fat content.
      In an animal model, volume retention of Revolve-processed fat grafts was
      significantly greater than decanted samples. The Revolve system presents a fat
      processing option that was less time-consuming, easier to use, and more efficient
      in this study than standard centrifugation or decantation.

PMID- 24676415
TI  - Evaluation of the American Society of Anesthesiologists Physical Status
      classification system in risk assessment for plastic and reconstructive surgery
      patients.
AB  - BACKGROUND: The American Society of Anesthesiologists Physical Status (ASA-PS)
      classification is a ranking system that quantifies patient health before
      anesthesia and surgery. Some surgical disciplines apply the ASA-PS to gauge a
      patient's likelihood of developing postoperative complications. OBJECTIVE: In
      this study, the authors analyze whether ASA-PS scores can successfully predict
      risk for postoperative complications in plastic and reconstructive operations.
      METHODS: The authors retrospectively reviewed the charts of 1801 patient
      procedures and selected for inclusion 1794 complex plastic and reconstructive
      operations that took place at 1 of several academic medical institutions between
      January 2008 and January 2012. ASA-PS scores, patient comorbidities, and
      postoperative complications were analyzed. Percentile data were treated with
      tests for proportions. Nonpercentile data were analyzed through comparison of
      means (t test). Low-risk (ASA 1-2) and high-risk (ASA 3+) groups were compared
      with simple odds ratios. RESULTS: For the 1430 women and 364 men in the patient
      cohort (average age, 49.5 years), the overall complication rate was 27.7%. When
      patients with complications were compared to those without, body mass index,
      operation time, recent major surgery, diabetes, hypertension, renal disease,
      cancer, and oral contraceptive use were statistically significant. After high
      risk (n = 398) and low-risk (n = 1396) groups were identified, infection, delayed
      wound healing, deep vein thrombosis, and overall complications had significantly
      increased incidence in the high risk group. Notably, deep vein thrombosis
      displayed the highest odds ratio (4.17) and a complication rate increase from
      0.93% to 3.77%. CONCLUSIONS: ASA-PS scores can be used either as substitutes for
      or as adjuncts to questionnaire-based risk assessment methods in plastic surgery.
      In addition to deducing significant findings for deep vein thrombosis incidence,
      ASA-PS scores hold important predictive associations for multiple non-venous
      thromboembolism complications, providing a broader measurement for postoperative
      complication risks. LEVEL OF EVIDENCE: 4.

PMID- 24676416
TI  - Evolutionary beauty.

PMID- 24676417
TI  - Modified nasal vestibule packing with airway preservation.

PMID- 24676418
TI  - Critical need for accurate and quantitative viability assays to optimize fat
      grafting protocols.

PMID- 24676419
TI  - Monopolar diathermy: 2 instruments, 1 hand.

PMID- 24676420
TI  - Expression and nuclear localization of the TATA-box-binding protein during
      baculovirus infection.
AB  - The TATA-box-binding protein (TBP) plays a key role in initiating eukaryotic
      transcription and is used by many viruses for viral transcription. We previously
      reported increased TBP levels during infection with the baculovirus Autographa
      californica multicapsid nuclear polyhedrovirus (AcMNPV). The TBP antiserum used
      in that study, however, cross-reacted with a baculoviral protein. Here, we
      reported that increased amounts of nuclear TBP were detected upon infection of
      Spodoptera frugiperda and TN-368 cells with a TBP-specific antiserum. TBP levels
      increased until 72 h post-infection (p.i.), whilst tbp transcripts decreased by
      16 h p.i., which suggested a virus-induced influence on the TBP protein levels.
      To address a potential modification of the TBP degradation pathway during
      infection, we investigated the possible role of viral ubiquitin. Infection
      studies with AcMNPV recombinants carrying a mutated viral ubiquitin gene revealed
      that the TBP increase during infection was not altered. In addition, pulse-chase
      experiments indicated a high TBP half-life of ~60 h in uninfected cells,
      suggesting that a virus-induced increase of TBP stability was unlikely. This
      increase in TBP correlated with a redistribution to nuclear domains resembling
      sites of viral DNA synthesis. Furthermore, we observed colocalization of TBP with
      host RNA polymerase (RNAP) II, but only until 8 h p.i., whilst TBP, but not
      RNAPII, was present in the enlarged replication domains late during infection.
      Thus, we suggested that AcMNPV adapted a mechanism to accumulate the highly
      stable cellular TBP at sites of viral DNA replication and transcription.

PMID- 24676421
TI  - Patient, carer and professional perspectives on barriers and facilitators to
      quality care in advanced heart failure.
AB  - BACKGROUND: Those with advanced heart failure (HF) experience high levels of
      morbidity and mortality, similar to common cancers. However, there remains
      evidence of inequity of access to palliative care services compared to people
      with cancer. This study examines patient, carer, and professional perspectives on
      current management of advanced HF and barriers and facilitators to improved care.
      METHODS: Qualitative study involving semi-structured interviews and focus groups
      with advanced HF patients (n = 30), carers (n = 20), and professionals (n = 65).
      Data analysed using Normalisation Process Theory (NPT) as the underpinning
      conceptual framework. FINDINGS: Uncertainty is ubiquitous in accounts from
      advanced HF patients and their caregivers. This uncertainty relates to
      understanding of the implications of their diagnosis, appropriate treatments, and
      when and how to seek effective help. Health professionals agree this is a major
      problem but feel they lack knowledge, opportunities, or adequate support to
      improve the situation. Fragmented care with lack of coordination and poor
      communication makes life difficult. Poor understanding of the condition extends
      to the wider circle of carers and means that requests for help may not be
      perceived as legitimate, and those with advanced HF are not prioritised for
      social and financial supports. Patient and caregiver accounts of emergency care
      are uniformly poor. Managing polypharmacy and enduring concomitant side effects
      is a major burden, and the potential for rationalisation exists. This study has
      potential limitations because it was undertaken within a single geographical
      location within the United Kingdom. CONCLUSIONS: Little progress is being made to
      improve care experiences for those with advanced HF. Even in the terminal stages,
      patients and caregivers are heavily and unnecessarily burdened by health care
      services that are poorly coordinated and offer fragmented care. There is evidence
      that these poor experiences could be improved to a large extent by simple
      organisational rather than complex clinical mechanisms.

PMID- 24676422
TI  - Bacillus subtilis as a platform for molecular characterisation of regulatory
      mechanisms of Enterococcus faecalis resistance against cell wall antibiotics.
AB  - To combat antibiotic resistance of Enterococcus faecalis, a better understanding
      of the molecular mechanisms, particularly of antibiotic detection, signal
      transduction and gene regulation is needed. Because molecular studies in this
      bacterium can be challenging, we aimed at exploiting the genetically highly
      tractable Gram-positive model organism Bacillus subtilis as a heterologous host.
      Two fundamentally different regulators of E. faecalis resistance against cell
      wall antibiotics, the bacitracin sensor BcrR and the vancomycin-sensing two
      component system VanSB-VanRB, were produced in B. subtilis and their functions
      were monitored using target promoters fused to reporter genes (lacZ and
      luxABCDE). The bacitracin resistance system BcrR-BcrAB of E. faecalis was fully
      functional in B. subtilis, both regarding regulation of bcrAB expression and
      resistance mediated by the transporter BcrAB. Removal of intrinsic bacitracin
      resistance of B. subtilis increased the sensitivity of the system. The lacZ and
      luxABCDE reporters were found to both offer sensitive detection of promoter
      induction on solid media, which is useful for screening of large mutant
      libraries. The VanSB-VanRB system displayed a gradual dose-response behaviour to
      vancomycin, but only when produced at low levels in the cell. Taken together, our
      data show that B. subtilis is a well-suited host for the molecular
      characterization of regulatory systems controlling resistance against cell wall
      active compounds in E. faecalis. Importantly, B. subtilis facilitates the careful
      adjustment of expression levels and genetic background required for full
      functionality of the introduced regulators. 

PMID- 24676423
TI  - Absolute quantification of protein copy number using a single-molecule-sensitive
      microarray.
AB  - We report the use of a microfluidic microarray incorporating single molecule
      detection for the absolute quantification of protein copy number in solution. In
      this paper we demonstrate protocols which enable calibration free detection for
      two protein detection assays. An EGFP protein assay has a limit of detection of
      <30 EGFP proteins in a microfluidic analysis chamber (limited by non-specific
      background binding), with a measured limit of linearity of approximately 6 *
      10(6) molecules of analyte in the analysis chamber and a dynamic range of >5
      orders of magnitude in protein concentration. An antibody sandwich assay was used
      to detect unlabelled human tumour suppressor protein p53 with a limit of
      detection of approximately 21 p53 proteins and a dynamic range of >3 orders of
      magnitude. We show that these protocols can be used to calibrate data
      retrospectively to determine the absolute protein copy number at the single cell
      level in two human cancer cell lines. 

PMID- 24676424
TI  - Neurofibromatosis type 1 gene mutation analysis using sequence capture and high
      throughput sequencing.
AB  - Neurofibromatosis type 1 syndrome (NF1) is caused by mutations in the NF1 gene.
      Availability of new sequencing technology prompted us to search for an
      alternative method for NF1 mutation analysis. Genomic DNA was isolated from
      saliva avoiding invasive sampling. The NF1 exons with an additional 50bp of
      flanking intronic sequences were captured and enriched using the SeqCap EZ Choice
      Library protocol. The captured DNA was sequenced with the Roche/454 GS Junior
      system. The mean coverages of the targeted regions were 41x and 74x in 2 separate
      sets of samples. An NF1 mutation was discovered in 10 out of 16 separate patient
      samples. Our study provides proof of principle that the sequence capture
      methodology combined with high-throughput sequencing is applicable to NF1
      mutation analysis. Deep intronic mutations may however remain undetectable, and
      change at the DNA level may not predict the outcome at the mRNA or protein
      levels. 

PMID- 24676426
TI  - Evaluation of the 7th edition of the TNM classification for lung cancer at a
      single institution.
AB  - PURPOSE: To assess the utilities and drawbacks of the 7th edition of the TNM
      classification for lung cancer. METHODS: Subjects included 1,469 patients who
      underwent pulmonary resection for primary non-small cell lung cancer. Survival
      characteristics were compared using the 6th and 7th editions of the staging
      system. RESULTS: According to the 6th and 7th editions, respectively, the 5-year
      survival rates based on stages were as follows: pStage IA (81.0, 81.0 %), pStage
      IB (70.6, 72.0 %), pStage IIA (61.3, 59.7 %), pStage IIB (56.6, 47.2 %), pStage
      IIIA (43.4, 37.6 %), pStage IIIB (8.9, 14.9 %), and pStage IV (14.0, 8.0 %).
      According to the 6th edition, there was no significant difference between pStages
      IB and IIA (P = 0.268), or between pStages IIA and IIB (P = 0.622), or between
      pStages IIIB and IV (P = 0.737). According to the 7th edition, there were
      significant differences between each adjacent stage group, except between pStages
      IIIB and IV (P = 0.424). According to the 7th edition staging system, 5-year
      survival rates by T classification were as follows: pT1a, 81.6 %; pT1b, 75.9 %;
      pT2a, 60.1 %; pT2b, 44.7 %; pT3, 24.4 %; and pT4, 13.2 %; with significant
      differences between each adjacent pT classification. The 5-year survival rates by
      M classification were as follows: M0, 57.2 %, M1a, 9.1 %, M1b, 0 %, with a
      significant difference between M0 and M1a, but there was no significant
      difference between M1a and M1b. CONCLUSION: The UICC 7th edition staging system
      is considered valid for non-small cell lung cancer patients and appears to be
      superior in defining different prognostic groups than the 6th edition.

PMID- 24676425
TI  - Rotavirus activates lymphocytes from non-obese diabetic mice by triggering toll
      like receptor 7 signaling and interferon production in plasmacytoid dendritic
      cells.
AB  - It has been proposed that rotavirus infection promotes the progression of
      genetically-predisposed children to type 1 diabetes, a chronic autoimmune disease
      marked by infiltration of activated lymphocytes into pancreatic islets. Non-obese
      diabetic (NOD) mice provide a model for the human disease. Infection of adult NOD
      mice with rhesus monkey rotavirus (RRV) accelerates diabetes onset, without
      evidence of pancreatic infection. Rather, RRV spreads to the pancreatic and
      mesenteric lymph nodes where its association with antigen-presenting cells,
      including dendritic cells, induces cellular maturation. RRV infection increases
      levels of the class I major histocompatibility complex on B cells and
      proinflammatory cytokine expression by T cells at these sites. In autoimmunity
      resistant mice and human mononuclear cells from blood, rotavirus-exposed
      plasmacytoid dendritic cells contribute to bystander polyclonal B cell activation
      through type I interferon expression. Here we tested the hypothesis that
      rotavirus induces bystander activation of lymphocytes from NOD mice by provoking
      dendritic cell activation and proinflammatory cytokine secretion. NOD mouse
      splenocytes were stimulated with rotavirus and assessed for activation by flow
      cytometry. This stimulation activated antigen-presenting cells and B cells
      independently of virus strain and replicative ability. Instead, activation
      depended on virus dose and was prevented by blockade of virus decapsidation,
      inhibition of endosomal acidification and interference with signaling through
      Toll-like receptor 7 and the type I interferon receptor. Plasmacytoid dendritic
      cells were more efficiently activated than conventional dendritic cells by RRV,
      and contributed to the activation of B and T cells, including islet-autoreactive
      CD8+ T cells. Thus, a double-stranded RNA virus can induce Toll-like receptor 7
      signaling, resulting in lymphocyte activation. Our findings suggest that
      bystander activation mediated by type I interferon contributes to the lymphocyte
      activation observed following RRV infection of NOD mice, and may play a role in
      diabetes acceleration by rotavirus. 

PMID- 24676427
TI  - Age at diagnosis on prostate cancer survival undergoing androgen deprivation
      therapy as primary treatment in daily practice: results from Japanese
      observational cohort.
AB  - OBJECTIVES: Primary androgen deprivation therapy (PADT) had been used extensively
      in Japan than in the USA and European countries regardless of the disease risk or
      patient's age. To illustrate the consequence of PADT from daily clinical
      practice, we evaluated the relationship among age, disease risk, and survival of
      patients with prostate cancer treated by PADT in largest Asian cohort. PATIENTS
      AND METHODS: The 19,246 men subjected to PADT enrolled in the Japan Study Group
      of Prostate Cancer were enrolled for the present analysis. Patients were divided
      into four groups based on age at diagnosis: age <66, 66-70, 71-75, and >75. Risk
      was stratified according to the Japan Cancer of the Prostate Risk Assessment (J
      CAPRA). Multivariate competing risks regression analysis was performed for OS and
      PFS. RESULTS: There was downward stage migration over age. Among men aged >75
      years, 34.1 % had nodal or distant metastatic disease. In contrast, 56.0 % of
      patients aged <66 years presented with advanced disease. The modality of hormonal
      therapy varied with age across risk groups; the younger age group showed a higher
      proportion of maximal androgen blockade, while the proportion of monotherapy use
      was higher in older men. The likelihood of low-risk disease by J-CAPRA
      classification increased significantly with increasing age (p < 0.0001 by
      Pearson's chi-square test). The same as OS, the PFS rate increased with age until
      after the age of 75. Men aged 71-75 had better survival rates even after
      adjustments for treatment modality alone, or for treatment modality plus disease
      risk. CONCLUSIONS: Age cohorts do affect orientation toward favorable disease
      course after PADT with men aged 71-75 being benefiting more from PADT than other
      age groups.

PMID- 24676430
TI  - A salt-bridge structure in solution revealed by 2D-IR spectroscopy.
AB  - Salt bridges are important interactions for the stability of protein
      conformations, but up to now it has been difficult to determine salt-bridge
      geometries in solution. Here we characterize the spatial structure of a salt
      bridge between guanidinium (Gdm(+)) and acetate (Ac(-)) using two-dimensional
      vibrational (2D-IR) spectroscopy. We find that as a result of salt bridge
      formation there is a significant change in the infrared response of Gdm(+) and
      Ac(-), and cross peaks between them appear in the 2D-IR spectrum. From the 2D-IR
      spectrum we determine the relative orientation of the transition-dipole moments
      of the vibrational modes of Gdm(+) and Ac(-), as well as the coupling between
      them. 

PMID- 24676429
TI  - The new histologic classification of lung primary adenocarcinoma subtypes is a
      reliable prognostic marker and identifies tumors with different mutation status:
      the experience of a French cohort.
AB  - BACKGROUND: Histologic classification of lung adenocarcinoma subtype has a
      prognostic value in most studies. However, lung adenocarcinoma characteristics
      differ across countries. Here, we aimed at validating the prognostic value of
      this classification in a large French series of lung adenocarcinoma. METHODS: We
      reviewed 407 consecutive lung adenocarcinomas operated on between 2001 and 2005
      and reclassified them according to the International Association for the Study of
      Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society
      (ERS) classification and subsequently graded them into low, intermediate, and
      high grade. We analyzed the relevance of this classification according to
      clinical, pathologic, and molecular analysis. RESULTS: Patients (median age, 61
      years; 288 men) underwent lobectomy (n = 378) or pneumonectomy (n = 29).
      Patients' overall survival at 5 and 10 years was 53.2% and 32.6%, respectively.
      Union for International Cancer Control stage distribution was 189 stage I, 104
      stage II, 107 stage III, and seven stage IV. Low-grade tumor was found in one
      patient, intermediate grade in 275 patients, and high grade in 131 patients. KRAS
      and EGFR mutations were detected in 34% and 9.6%, respectively. Histologic grade
      was significantly correlated with extent of resection (P = .01), thyroid
      transcriptional factor-1 expression (P = .00000001), vascular emboli (P = .03),
      and EGFR mutations (P = .01). Mucinous adenocarcinomas were associated with KRAS
      mutations (P = .003). At univariate analysis, age, extent of resection,
      histologic grade, pleural invasion, vascular emboli, pathologic T and N, and
      stage were predictive of survival. At multivariate analysis, age (P = .0001),
      histologic grade (P = .03), and stage (P = .000003) were independent prognostic
      factors. CONCLUSIONS: IASLC/ATS/ERS classification of lung adenocarcinomas
      predicts survival in French population. Histologic grade correlates with
      clinical, pathologic and molecular parameters suggesting different oncogenic
      pathways.

PMID- 24676428
TI  - Role of receptor for hyaluronan-mediated motility (RHAMM) in human head and neck
      cancers.
AB  - The receptor for hyaluronan (HA)-mediated motility (RHAMM) is a HA-binding
      protein located in the cytoskeleton and centrosome. RHAMM has multiple functions
      that manifest with different cellular localizations, for example, modulation of
      growth factor receptor, regulation of cell signaling pathways, and mitotic
      spindle assembly. In addition, its increased expression has major roles in
      tumorigenesis and can induce genomic instability and cancer progression. In head
      and neck cancers, increased expression of RHAMM is associated with high
      proliferation of cancer cells and decreased survival. CD44, a cell-adhesion
      molecule and HA receptor, can modulate intracellular signaling by forming
      complexes with RHAMM to promote invasion and metastasis of cancer cells. In this
      review, we provide an overview of the biological functions of RHAMM in non
      neoplastic cells and cancer cells, as well as its association with CD44, and also
      introduce studies that particularly implicate RHAMM in the pathogenesis of head
      and neck cancers. 

PMID- 24676431
TI  - Impairment of quality of life and cognition in demyelinating neuropathies:
      targets to be considered from diagnosis to treatment?

PMID- 24676432
TI  - The neurofibromatosis: which one and why?

PMID- 24676433
TI  - Chronic inflammatory demyelinating polyneuropathy: quality of life,
      sociodemographic profile and physical complaints.
AB  - Whereas an evaluation of quality of life and possible impacts on the mental state
      of a patient may help to evaluate the evolution of chronic inflammatory
      demyelinating polyneuropathy (CIDP), the aim of this study was to study the
      psychological profile of patients, and evaluate quality of life associated with
      the disease. METHOD: 41 patients were evaluated using a Mini-Mental State
      Examination (MMSE) and a Short-Form Health Survey (SF-36). RESULTS: The mean age
      of the patients was 50.6 years, 63.4% men. Of the participants, 65.9% had other
      health problems, 39% reported needing help with activities of daily living, 49%
      slept less than 8 hours per night, and 34.1% complained of some memory deficit.
      The average MMSE score was 26. Impairment of functional capacity and pain were
      the more important altered health states. CONCLUSION: CIDP has important social
      and economic impacts, owing to functional impairments that can lead to
      professional and personal limitations.

PMID- 24676434
TI  - Memory in children with symptomatic temporal lobe epilepsy.
AB  - In children with temporal lobe epilepsy (TLE), memory deficit is not so well
      understood as it is in adults. The aim of this study was to identify and describe
      memory deficits in children with symptomatic TLE, and to verify the influence of
      epilepsy variables on memory. We evaluated 25 children with TLE diagnosed on
      clinical, EEG and MRI findings. Twenty-five normal children were compared with
      the patients. All children underwent a neuropsychological assessment to estimate
      intellectual level, attention, visual perception, handedness, and memory
      processes (verbal and visual: short-term memory, learning, and delayed recall).
      The results allowed us to conclude: besides memory deficits, other
      neuropsychological disturbances may be found in children with TLE such as
      attention, even in the absence of overall cognitive deficit; the earlier onset of
      epilepsy, the worse verbal stimuli storage; mesial lesions correlate with
      impairment in memory storage stage while neocortical temporal lesions correlate
      with retrieval deficits. 

PMID- 24676436
TI  - Ability of aphasic individuals to perform numerical processing and calculation
      tasks.
AB  - OBJECTIVE: To compare performance on EC301 battery calculation task between
      aphasic subjects and normal controls of the same sex, age, and education. METHOD:
      Thirty-two aphasic patients who had suffered a single left hemisphere stroke were
      evaluated. Forty-four healthy volunteers were also selected. All subjects
      underwent a comprehensive arithmetic battery to assess their numerical and
      calculation skills. Performances on numerical processing and calculation tasks
      were then analyzed. RESULTS: Aphasic individuals showed changes in their ability
      to perform numerical processing and calculation tasks that were not observed in
      the healthy population. CONCLUSION: Compared with healthy subjects of the same
      age and education level, individuals with aphasia had difficulty performing
      various tasks that involved numerical processing and calculation.

PMID- 24676435
TI  - Treadmill training as an augmentation treatment for Alzheimer's disease: a pilot
      randomized controlled study.
AB  - OBJECTIVE: To assess the effect of aerobic exercise on the cognition and
      functional capacity in Alzheimer's disease (AD) patients. METHOD: Elderly (n=20)
      with mild dementia (NINCDS-ADRDA/CDR1) were randomly assigned to an exercise
      group (EG) on a treadmill (30 minutes, twice a week and moderate intensity of 60%
      VO2max) and control group (GC) 10 patients. The primary outcome measure was the
      cognitive function using Cambridge Cognitive Examination (CAMCOG). Specifics
      instruments were also applied to evaluate executive function, memory, attention
      and concentration, cognitive flexibility, inhibitory control and functional
      capacity. RESULTS: After 16 weeks, the EG showed improvement in cognition CAMCOG
      whereas the CG declined. Compared to the CG, the EG presented significant
      improvement on the functional capacity. The analysis of the effect size has shown
      a favorable response to the physical exercise in all dependent variables.
      CONCLUSION: Walking on treadmill may be recommended as an augmentation treatment
      for patients with AD.

PMID- 24676437
TI  - Higher risk of complications in odynophagia-associated dysphagia in amyotrophic
      lateral sclerosis.
AB  - OBJECTIVE: This investigation aimed to identify associated factors with dysphagia
      severity in amyotrophic lateral sclerosis (ALS). METHOD: We performed a cross
      sectional study of 49 patients with ALS. All patients underwent fiberoptic
      endoscopy evaluation of swallowing and answered a verbal questionnaire about
      swallowing complaints. The patients were divided into groups according to
      dysphagia severity. RESULTS: Among the factors analyzed, only odynophagia was
      associated with moderate or severe dysphagia. CONCLUSION: Odynophagia was
      associated with moderate and severe dysphagia in ALS and suggests a high risk of
      pulmonary and nutritional complications.

PMID- 24676438
TI  - Initial circulatory response to active standing in Parkinson's disease without
      typical orthostatic hypotension.
AB  - While the circulatory response to orthostatic stress has been already evaluated
      in Parkinson's disease patients without typical orthostatic hypotension (PD-TOH),
      there is an initial response to the upright position which is uniquely associated
      with active standing (AS). We sought to assess this response and to compare it to
      that seen in young healthy controls (YHC). METHOD: In 10 PD-TOH patients (8
      males, 60 +/- 7 years, Hoehn and Yahr <= 3) the changes in systolic blood
      pressure (SBP) and heart rate that occur in the first 30 seconds (sec) of
      standing were examined. Both parameters were non-invasively and continuously
      monitored using the volume-clamp method by Penaz and the Physiocal criteria by
      Wesseling. The choice of sample points was prompted by the results of previous
      studies. These sample points were compared to those of 10 YHC (8 males, 32 +/- 8
      years). RESULTS: The main finding of the present investigation was an increased
      time between the AS onset and SBP overshoot in PD-TOH group (24 +/- 4 vs. 19 +/-
      3 sec; p<0.05). CONCLUSION: This delay might reflect a prolonged latency in the
      baroreflex-mediated vascular resistance response, but more studies are needed to
      confirm this preliminary hypothesis.

PMID- 24676439
TI  - Niemann-Pick disease type C: a case series of Brazilian patients.
AB  - The aim of the study was to analyze a series of Brazilian patients with Niemann
      Pick disease type C (NP-C). METHOD: Correlations between clinical findings,
      laboratory data, molecular findings and treatment response are presented. RESULT:
      The sample consisted of 5 patients aged 8 to 26 years. Vertical supranuclear gaze
      palsy, cerebellar ataxia, dementia, dystonia and dysarthria were present in all
      cases. Filipin staining showed the "classical" pattern in two patients and a
      "variant" pattern in three patients. Molecular analysis found mutations in the
      NPC1 gene in all alleles. Miglustat treatment was administered to 4 patients.
      CONCLUSION: Although filipin staining should be used to confirm the diagnosis,
      bone marrow sea-blue histiocytes often help to diagnosis of NP-C. The p.P1007A
      mutation seems to be correlated with the "variant" pattern in filipin staining.
      Miglustat treatment response seems to be correlated with the age at disease onset
      and disability scale score at diagnosis.

PMID- 24676440
TI  - Clinical features and management of hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) is a group of genetically-determined
      disorders characterized by progressive spasticity and weakness of lower limbs. An
      apparently sporadic case of adult-onset spastic paraplegia is a frequent clinical
      problem and a significant proportion of cases are likely to be of genetic origin.
      HSP is clinically divided into pure and complicated forms. The later present with
      a wide range of additional neurological and systemic features. To date, there are
      up to 60 genetic subtypes described. All modes of monogenic inheritance have been
      described: autosomal dominant, autosomal recessive, X-linked and mitochondrial
      traits. Recent advances point to abnormal axonal transport as a key mechanism
      leading to the degeneration of the long motor neuron axons in the central nervous
      system in HSP. In this review we aim to address recent advances in the field,
      placing emphasis on key diagnostic features that will help practicing
      neurologists to identify and manage these conditions.

PMID- 24676441
TI  - Biological markers of Alzheimer's disease.
AB  - The challenges for establishing an early diagnosis of Alzheimer's disease (AD)
      have created a need for biomarkers that reflect the core pathology of the
      disease. The cerebrospinal fluid (CSF) levels of total Tau (T-tau),
      phosphorylated Tau (P-Tau) and beta-amyloid peptide (Abeta42) reflect,
      respectively, neurofibrillary tangle and amyloid pathologies and are considered
      as surrogate markers of AD pathophysiology. The combination of low Abeta42 and
      high levels of T-tau and P-Tau can accurately identify patients with AD at early
      stages, even before the development of dementia. The combined analysis of the CSF
      biomarkers is also helpful for the differential diagnosis between AD and other
      degenerative dementias. The development of these CSF biomarkers has evolved to a
      novel diagnostic definition of the disease. The identification of a specific
      clinical phenotype combined with the in vivo evidence of pathophysiological
      markers offers the possibility to make a diagnosis of AD before the dementia
      stage with high specificity.

PMID- 24676442
TI  - Adult onset sporadic ataxias: a diagnostic challenge.
AB  - Patients with adult onset non-familial progressive ataxia are classified in
      sporadic ataxia group. There are several disease categories that may manifest
      with sporadic ataxia: toxic causes, immune-mediated ataxias, vitamin deficiency,
      infectious diseases, degenerative disorders and even genetic conditions.
      Considering heterogeneity in the clinical spectrum of sporadic ataxias, the
      correct diagnosis remains a clinical challenge. In this review, the different
      disease categories that lead to sporadic ataxia with adult onset are discussed
      with special emphasis on their clinical and neuroimaging features, and diagnostic
      criteria. 

PMID- 24676443
TI  - Neurofibromatoses: part 1 - diagnosis and differential diagnosis.
AB  - Neurofibromatoses (NF) are a group of genetic multiple tumor growing
      predisposition diseases: neurofibromatosis type 1 (NF1), neurofibromatosis type 2
      (NF2) and schwannomatosis (SCH), which have in common the neural origin of tumors
      and cutaneous signs. They affect nearly 80 thousand of Brazilians. In recent
      years, the increased scientific knowledge on NF has allowed better clinical
      management and reduced complication morbidity, resulting in higher quality of
      life for NF patients. In most cases, neurology, psychiatry, dermatology, clinical
      geneticists, oncology and internal medicine specialists are able to make the
      differential diagnosis between NF and other diseases and to identify major NF
      complications. Nevertheless, due to its great variability in phenotype
      expression, progressive course, multiple organs involvement and unpredictable
      natural evolution, NF often requires the support of neurofibromatoses specialists
      for proper treatment and genetic counseling. This Part 1 offers step-by-step
      guidelines for NF differential diagnosis. Part 2 will present the NF clinical
      management. 

PMID- 24676445
TI  - Hemichorea in tuberculous meningitis.

PMID- 24676444
TI  - The history of neurosurgery at the University of Sao Paulo.
AB  - The history of neurosurgery at University of Sao Paulo comes from 1918, since its
      origins under the Department of Neurology from Chair of Psychiatric Clinic and
      Nervous Diseases. Professor Enjolras Vampre was the great inspiration for such
      medical specialty in the State of Sao Paulo. In 1929, the first neurosurgical
      procedures were performed in the recently (at time) organized Section of
      Neurosurgery. The official inauguration of the Division of Functional
      Neurosurgery occurred at June 1977, with the presence of worldwide well-known
      neuroscientists. The division suffered a deep streamlining under the leadership
      of Professor Raul Marino Jr., between the decades of 1990 and 2000. At this time,
      it was structured with the sections of neurological surgery, functional
      neurosurgery and neurosurgical emergency. Since 2008, Professor Manoel Jacobsen
      Teixeira is the Chairman of the Division and has provided the Division with the
      best available technological resources, performing more than 3,000 surgeries a
      year and training professionals who will, certainly, be some of the future
      leaders of brazilian neurosurgery. 

PMID- 24676446
TI  - Resolution of MRI findings of copper deficiency myeloneuropathy in a patient with
      Wilson's disease.

PMID- 24676447
TI  - H7N9 bird flu: emerging of psychological problem.

PMID- 24676448
TI  - Opinion on Why should we use atraumatic needles in lumbar puncture?, by SLA
      Matas.

PMID- 24676449
TI  - Neurological complications in dengue infection.

PMID- 24676450
TI  - Neurocysticercosis.

PMID- 24676451
TI  - Eosinophilic meningitis due to Angiostrongylus cantonensis with confirmed finding
      of intrathecal parasite.

PMID- 24676452
TI  - H6N1 bird flu: new emerging infection that the neurologist has to prepare for
      management.

PMID- 24676453
TI  - Diagnosis criteria of dengue encephalitis.

PMID- 24676454
TI  - Vigilin is overexpressed in hepatocellular carcinoma and is required for HCC cell
      proliferation and tumor growth.
AB  - Vigilin contains multiple KH domains and is an evolutionarily conserved RNA
      binding protein from yeast to the human. Its reported roles in human
      carcinogenesis are controversial in different types of human cancers. To obtain
      the specific expression profiles of vigilin in human hepatocellular carcinomas
      (HCCs), we examined vigilin protein levels in normal human liver, liver
      cirrhosis, adjacent non-tumor liver and HCC tumor tissues as well as in several
      HCC cell lines. We discovered that vigilin expression increased progressively
      from the liver cirrhosis tissue to adjacent non-tumor liver tissue and then to
      HCC tumor cells. Vigilin protein was also overexpressed in all three HCC cell
      lines examined, HepG2, BEL7402 and SMMC7721, when compared with the vigilin
      expression level in the L-02 human embryonic hepatocyte cell line. We further
      investigated the impact of vigilin knockdown on HCC cell proliferation, survival,
      motility, tumor growth and sensitivity to chemotherapy. We found that knockdown
      of vigilin in the BEL7402 HCC cells significantly inhibited their proliferation,
      colony formation and migration, but largely enhanced the cisplatin treatment
      induced growth inhibition of these cells in culture. We also found that vigilin
      knockdown effectively inhibited the growth of BEL7402 cell-derived xenograft
      tumors in nude mice by decreasing the proliferation and increasing the apoptosis
      of the BEL7402 HCC cells. Taken together, these results suggest that
      progressively upregulated vigilin may serve as a molecular risk marker for HCC
      development, and targeting vigilin may help to inhibit HCC cell growth, survival
      and migration.

PMID- 24676457
TI  - Confinement stabilises single crystal vaterite rods.
AB  - Single-crystals of vaterite, the least-stable anhydrous polymorph of CaCO3, are
      rare in biogenic and synthetic systems. We here describe the synthesis of high
      aspect ratio single crystal vaterite rods under additive-free conditions by
      precipitating CaCO3 within the cylindrical pores of track-etch membranes. 

PMID- 24676455
TI  - The common traits of the ACC and PFC in anxiety disorders in the DSM-5: meta
      analysis of voxel-based morphometry studies.
AB  - BACKGROUND: The core domains of social anxiety disorder (SAD), generalized
      anxiety disorder (GAD), panic disorder (PD) with and without agoraphobia (GA),
      and specific phobia (SP) are cognitive and physical symptoms that are related to
      the experience of fear and anxiety. It remains unclear whether these highly
      comorbid conditions that constitute the anxiety disorder subgroups of the
      Diagnostic and Statistical Manual for Mental Disorders--Fifth Edition (DSM-5)
      represent distinct disorders or alternative presentations of a single underlying
      pathology. METHODS: A systematic search of voxel-based morphometry (VBM) studies
      of SAD, GAD, PD, GA, and SP was performed with an effect-size signed differential
      mapping (ES-SDM) meta-analysis to estimate the clusters of significant gray
      matter differences between patients and controls. RESULTS: Twenty-four studies
      were eligible for inclusion in the meta-analysis. Reductions in the right
      anterior cingulate gyrus and the left inferior frontal gyrus gray matter volumes
      (GMVs) were noted in patients with anxiety disorders when potential confounders,
      such as comorbid major depressive disorder (MDD), age, and antidepressant use
      were controlled for. We also demonstrated increased GMVs in the right
      dorsolateral prefrontal cortex (DLPFC) in comorbid depression-anxiety (CDA), drug
      naive and adult patients. Furthermore, we identified a reduced left middle
      temporal gyrus and right precentral gyrus in anxiety patients without comorbid
      MDD. CONCLUSION: Our findings indicate that a reduced volume of the right ventral
      anterior cingulate gyrus and left inferior frontal gyrus is common in anxiety
      disorders and is independent of comorbid depression, medication use, and age.
      This generic effect supports the notion that the four types of anxiety disorders
      have a clear degree of overlap that may reflect shared etiological mechanisms.
      The results are consistent with neuroanatomical DLPFC models of physiological
      responses, such as worry and fear, and the importance of the ventral anterior
      cingulate (ACC)/medial prefrontal cortex (mPFC) in mediating anxiety symptoms.

PMID- 24676456
TI  - The combination of rapamycin and MAPK inhibitors enhances the growth inhibitory
      effect on Nara-H cells.
AB  - The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway
      promotes the initiation of autophagy, and the mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated protein kinase (ERK) is well known to
      induce autophagy. Autophagy is a self-defense mechanism of cancer cells that are
      subjected to antitumor agents, and blocking autophagy can trigger apoptosis. In
      the present study, we demonstrate that an mTOR inhibitor, rapamycin, induces
      autophagy in the Nara-H malignant fibrous histiocytoma (MFH) cell line through
      the activation of ERK1/2. Rapamycin-induced apoptosis was enhanced following the
      inhibition of the MEK/ERK pathway. In the Nara-H cells, we examined the effects
      of rapamycin treatment on cell proliferation and on the phosphorylation of the
      mTOR pathway components and autophagy by western blot analysis. Furthermore, we
      examined the effects of rapamycin with or without the MEK inhibitor, U0126, on
      the induction of apoptosis by using fluorescence microscopy. Rapamycin inhibited
      Nara-H cell proliferation and decreased the phosphorylation of the mTOR pathway
      in the Nara-H cells. Rapamycin induced the apoptosis of Nara-H cells, and this
      apoptosis was enhanced by U0126. Simultaneously, phospho-ERK1/2 was activated by
      rapamycin. The present study demonstrates that rapamycin induces autophagy in
      Nara-H cells by activating the MEK/ERK signaling pathway, and the rapamycin
      induced apoptosis can be enhanced by the MEK inhibitor, U0126. These results
      suggest that self-protective mechanisms involving mTOR inhibitors in Nara-H cells
      are prevented by the inhibition of the MEK/ERK pathway. The combination of an
      mTOR inhibitor (e.g., rapamycin) and an MEK inhibitor (e.g., U0126) may offer
      effective treatment for MFH, as this combination effectively activates apoptotic
      pathways.

PMID- 24676458
TI  - Contribution of Charles Estienne (1504-1564) to the study of syringomyelia.

PMID- 24676460
TI  - Effects of the magnitude of pressure on the severity of injury and capillary
      closure in rat experimental pressure ulcers.
AB  - Experimental pressure ulcers were successfully produced in the rat abdominal wall
      at 100 mmHg in our previous study. We hypothesized that injury is less severe
      when pressures are lower than 100 mmHg and explored a critical pressure in the
      production of pressure ulcers. At 70 and 60 mmHg, repeated compressions for 4 h
      daily for 5 consecutive days resulted in partial skin necrosis and eschar
      formation in the majority of rats, whereas skin injuries were absent or very mild
      in most of the rats at 50 mmHg. The extent of ischemia was also examined by
      visualization of capillary blood flow using intravascular infusion of
      Lycopersicon esculentum lectin. Rat abdominal walls were compressed in the range
      from 0 (control) to 100 mmHg. The percentages of open capillaries were 62.8 +/-
      10.1% at 0 mmHg and 34.7 +/- 18.5% at 10 mmHg. The ratio of open capillaries was
      further decreased with increasing pressure, but not pressure dependently. In
      conclusion, the severity of injury at 50 mmHg was drastically milder than that at
      60 mmHg or higher, whereas the extent of ischemia (capillary closure) was not
      significantly different. The pressure is vitally important; however, other
      factor(s) besides ischemia is likely to promote the development of pressure
      ulcers.

PMID- 24676459
TI  - CD56-positive adult T-cell leukemia/lymphoma: a case report and a review of the
      literature.
AB  - A 67-year-old woman presented with a swelling on both sides of the neck. Biopsy
      of an enlarged cervical lymph node on the left side and flow cytometric analysis
      revealed CD56-positive CD4(+)CD8(+) abnormal NK/T cells. A Southern blot analysis
      of the cervical lymph node biopsy specimen showed a human T-cell leukemia virus
      type 1 provirus DNA monoclonal band. Based on these findings, the patient was
      diagnosed with CD56-positive adult T-cell leukemia/lymphoma. After five cycles of
      cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, the general
      condition of the patient gradually declined, indicating resistance to treatment,
      and approximately 9 months after the onset of symptoms, the patient died. CD56 is
      recognized as an unfavorable prognostic marker in cases of acute myeloid leukemia
      with t(8;21), acute promyelocytic leukemia, and anaplastic large cell lymphoma.
      Only eight cases of CD56-positive adult T-cell leukemia/lymphoma have been
      reported so far in the literature. Most of these cases were in the advanced stage
      at diagnosis and had poor outcomes. It appears that the correlation between CD56
      expression and outcomes in patients with adult T-cell leukemia/lymphoma should be
      clarified by investigating a larger number of cases in the future. 

PMID- 24676461
TI  - Methylisothiazolinone contact allergy is rising to alarming heights also in
      southern Sweden.
AB  - The preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a
      well-known sensitiser and present in most baseline series since at least 20
      years. The proportions of MCI/MI are 3:1. MI alone has been used as a
      preservative in occupational and household products, and cosmetics since less
      than 10 years. MCI/MI tested at 100 ppm fails to detect a significant percentage
      of contact-allergic reactions to MI. Our aim was to investigate whether a
      separate test preparation with MI picks up additional cases of contact allergy to
      MI not detected with MCI/MI 200 ppm. MI was inserted into the baseline series of
      the Malmo clinic in 2003 starting at 475 ppm, then 900 ppm, then 1,000 ppm, 1,500
      ppm and finally 2,000 ppm. In 5,881 consecutively tested dermatitis patients the
      contact allergy rate for MI varied between 0.5 and 6.5%, with a marked increase
      in recent years. The contact allergy rate to MI 2,000 ppm alone, not traced by
      MCI/MI 200 ppm, varied between 0 and 1.9 %. In conclusion, due to the increase of
      contact allergy to MI not traced by MCI/MI 200 ppm, MI in water at 2,000 ppm
      should be tested in a baseline series. Independent of patch test technique a dose
      of 60 ug/cm should not be exceeded to avoid adverse reactions and particularly
      patch test sensitisation. 

PMID- 24676462
TI  - Multilocus genotype and subtype analysis of Cryptosporidium andersoni derived
      from a Bactrian camel (Camelus bactrianus) in China.
AB  - Fecal specimens from two Bactrian camels were collected in the Ya'an city zoo of
      China and were examined for Cryptosporidium by centrifugal flotation. One
      specimen was found to be parasitized by Cryptosporidium via microscopy, and the
      oocysts were measured to have an average size of 7.03 * 5.50 MUm (n > 50). The
      isolate was genotyped by polymerase chain reaction (PCR) amplification and DNA
      sequence analysis of the partial 18S rRNA, COWP, and A135 genes, and was
      confirmed to be Cryptosporidium andersoni with minor nucleotide differences.
      Multilocus sequence typing (MLST) analysis indicated that the subtype of the
      camel-derived C. andersoni isolate was A4, A4, A4, and A1 at the four
      minisatellite loci (MS1, MS2, MS3, and MS16, respectively). Therefore, this
      isolate belongs to the most common MLST subtype reported in cattle in China and
      is distinct from two other known camel C. andersoni MLST subtypes (A6, A4, A2, A1
      and A6, A5, A2, A1). Animal transmission experiments demonstrated that the C.
      andersoni isolate was not infectious to immunosuppressed or immunocompetent Kun
      ming mice, Sprague-Dawley rats, and hamsters but was biologically similar to most
      bovine C. andersoni isolates characterized so far. Therefore, transmission of
      this camel-derived C. andersoni isolate is very likely to occur between camels
      and bovine. 

PMID- 24676463
TI  - Multiple ethnic origins of mitochondrial DNA lineages for the population of
      Mauritius.
AB  - This article reports on the first genetic assessment of the contemporary
      Mauritian population. Small island nodes such as Mauritius played a critical role
      in historic globalization processes and revealing high-resolution details of
      labour sourcing is crucial in order to better understand early-modern diaspora
      events. Mauritius is a particularly interesting case given detailed historic
      accounts attesting to European (Dutch, French and British), African and Asian
      points of origin. Ninety-seven samples were analysed for mitochondrial DNA to
      begin unravelling the complex dynamics of the island's modern population. In
      corroboration with general demographic information, the majority of maternal
      lineages were derived from South Asia (58.76%), with Malagasy (16.60%),
      East/Southeast Asian (11.34%) and Sub-Saharan African (10.21%) also making
      significant contributions. This study pinpoints specific regional origins for the
      South Asian genetic contribution, showing a greater influence on the contemporary
      population from northern and southeast India. Moreover, the analysis of lineages
      related to the slave trade demonstrated that Madagascar and East Asia were the
      main centres of origin, with less influence from West Africa. 

PMID- 24676465
TI  - Assessment of genetic variability of fish personality traits using rainbow trout
      isogenic lines.
AB  - The study of inter-individual variability of personality in fish is a growing
      field of interest but the genetic basis of this complex trait is still poorly
      investigated due to the difficulty in controlling fish genetic origin and life
      history. When available, isogenic lines that allow performing independent tests
      on different individuals having identical genotype constitute a very relevant
      experimental material to disentangle the genetic and environmental components of
      behavioural individuality. We took advantage of heterozygous isogenic lines to
      investigate the personality in rainbow trout through the analysis of their
      reactions to different experimental situations. To this end, seven to ten rainbow
      trout isogenic lines were screened for their spatial exploratory behaviour, their
      flight response toward a stressor and their risk taking behaviour. Results showed
      that some lines seemed less sensitive to new events or environmental changes and
      could be defined as low responsive, while others were very sensitive and defined
      as high responsive. The use of isogenic lines highlighted the importance of
      genetic factors, in combination with life history, in the expression of
      personality in domesticated fish. 

PMID- 24676466
TI  - The structural diversity and photoluminescent properties of cadmium
      thiophenedicarboxylate coordination polymers.
AB  - Two series of Cd(II) coordination polymers (CPs), {[Cd(bimm)2(H2O)2][(3,4
      tdc)2][H2O]2}n (1a), [Cd(3,4-tdc)(bimb)]n (2a), [Cd(3,4-tdc)(bimpy)(H2O)]n (3a)
      and [Cd(2,3-Htdc)2(bimm)2]n (1b), {[Cd(2,3-tdc)(bimb)](H2O)}n (2b), [Cd(2,3
      tdc)(bimpy)(H2O)]n (3b) where H2tdc = thiophenedicarboxylic acid, bimm = 1,2
      bis(imidazol-1'-yl)methane, bimb = 1,2-bis(imidazol-1'-yl)butane and bimpy = 3,5
      bis(imidazol-1'-yl)pyridine, have been synthesized by using Cd(II) acetate with
      H2tdc and N-donor ligands under hydrothermal conditions. Two related isomeric
      thiophenedicarboxylic acids were chosen to examine the positional isomeric effect
      on the construction of these CPs with distinct dimensionality and connectivity.
      The structure of 1a is a one-dimensional (1D) cationic double chain further
      forming a two-dimensional (2D) supramolecular network via hydrogen-bonding
      interactions, while 1b exhibits a neutral double chain structure. Interestingly,
      a three-dimensional (3D) 4-connected cds network for 2a as well as a 1D neutral
      double chain structure for 2b were obtained in the presence of bimb. When the
      rigid tripodal bimpy was introduced, isomorphous 3a and 3b with 3D (3,5)
      connected (6(2).8) (6(7).8(3)) nets were constructed. The structural diversity of
      1a-2b mainly stems from the positional isomeric effect of thiophenedicarboxylate,
      while 3a and 3b are well regulated by rigid bimpy. Moreover, the thermal
      stability and photoluminescence of 1a-3b are investigated.

PMID- 24676464
TI  - Adolescent drinking and motivated decision-making: a cotwin-control investigation
      with monozygotic twins.
AB  - The present study used a monozygotic (MZ) cotwin-control (CTC) design to
      investigate associations between alcohol use and performance on the Iowa gambling
      task (IGT) in a sample of 96 adolescents (half female). The MZ CTC design is well
      suited to shed light on whether poor decision-making, as reflected on IGT
      performance, predisposes individuals to abuse substances or is a consequence of
      use. Participants completed structural MRI scans as well, from which we derived
      gray matter volumes for cortical and subcortical regions involved in IGT
      performance and reduced in adolescents with problematic alcohol use. Drinking was
      associated with poorer task performance and with reduced volume of the left
      lateral orbital-frontal cortex. CTC analyses indicated that the former was due to
      differences between members of twin pairs in alcohol use (suggesting a causal
      effect of alcohol), whereas the latter was due to factors shared by twins
      (consistent with a pre-existing vulnerability for use). Although these
      preliminary findings warrant replication, they suggest that normative levels of
      alcohol use may diminish the quality of adolescent decision-making and thus have
      potentially important public health implications. 

PMID- 24676467
TI  - Anti-inflammatory effect of resveratrol on adjuvant arthritis rats with abnormal
      immunological function via the reduction of cyclooxygenase-2 and prostaglandin
      E2.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease with unknown
      etiology. The present study investigated the anti-inflammatory effect of
      resveratrol on rats with adjuvant arthritis (AA) with abnormal immunological
      function via the reduction of cyclooxygenase-2 (COX-2) and prostaglandin E2
      (PGE2). AA model rats were established by injection of complete Freund's adjuvant
      and alterations in the rats secondary paw swelling and the polyarthritic scores
      were observed. Pathological examination of joint tissues was observed by
      hematoxylin and eosin staining. The proliferation of spleen cells was examined
      using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in
      vitro. The protein expression of COX-2 in the synovial tissues was detected by
      western blotting. The level of PGE2 in the serum was assayed using an ELISA kit.
      The results demonstrated that resveratrol (10 or 50 mg/kg) was able to
      significantly reduce paw swelling and decrease the arthritis scores. Compared
      with the AA model rats, a significant reduction in the proliferation of
      concanavalin A-stimulated spleen cells was observed, articular cartilage
      degeneration with synovial hyperplasia and inflammatory cell infiltration was
      suppressed and the production of COX-2 and PGE2 in AA rats was reduced by
      treatment with resveratrol. These results suggest that resveratrol has
      significant anti-inflammatory effects on AA rats, which may be associated with
      the reduction of COX-2 and PGE2 inflammatory mediators.

PMID- 24676468
TI  - A systematic review of psychosocial factors associated with emotional adjustment
      in in vitro fertilization patients.
AB  - BACKGROUND: IVF treatment is usually stressful for patients, but individual
      differences in emotional response do exist. Differences in the stress response
      may be related to reproductive outcomes as well as to the development of
      psychiatric problems. This review collates research exploring which psychosocial
      factors (e.g. personality traits and coping strategies) are associated with the
      emotional adjustment of IVF patients. The aim is to reveal what is currently
      known about risk and protective factors for coping with the stress of IVF
      treatment and where further enquiry would be most beneficial. METHODS: The
      databases, MEDLINE/PUBMED (US National Library of Medicine), PsycINFO (American
      Psychological Association), Web of Science (Social Sciences Citation Index) and
      EMbase, were searched from 1978 to September 2012 using relevant key words. All
      published peer-reviewed studies exploring associations between psychosocial
      factors and emotional adjustment outcomes were considered for inclusion. RESULTS:
      There were 23 studies identified for review. One-third of the psychosocial
      factors explored were found to be significantly related to emotional adjustment
      outcome measures. Neuroticism and the use of escapist coping strategies were
      positively associated with distress by multiple studies. Social support was
      negatively associated with distress by several studies. A number of other
      psychosocial variables appear to be associated with distress, including self
      criticism, dependency, situation appraisals and attachment style, but these have
      only been explored by one or two studies at most. There is a paucity of research
      using positive emotional outcome measures (e.g. well-being, positive affect,
      happiness or life satisfaction) to quantify emotional adjustment. CONCLUSIONS:
      Whilst some psychosocial variables appear to be consistently associated with
      distress for IVF patients, two-thirds of the variables tested to date do not
      appear to be associated with emotional adjustment. This review highlights key
      psychosocial factors to assist the identification of patients at high risk of
      psychological distress. These findings highlight at least two psychological
      factors that may be amenable to alteration with psychological or educational
      interventions. Future work should explore whether experimental manipulation of
      such psychosocial factors can provide effective stress reduction in this clinical
      context.

PMID- 24676470
TI  - A quantum Monte Carlo study on electron correlation in all-metal aromatic
      clusters MAl4(-) (M = Li, Na, K, Rb, Cu, Ag and Au).
AB  - Using fixed-node diffusion quantum Monte Carlo (FN-DMC) simulation we investigate
      the electron correlation in all-metal aromatic clusters MAl4(-) (with M = Li, Na,
      K, Rb, Cu, Ag and Au). The electron detachment energies and electron affinities
      of the clusters are obtained. The vertical electron detachment energies obtained
      from the FN-DMC calculations are in very good agreement with the available
      experimental results. Calculations are also performed within the Hartree-Fock
      approximation, density-functional theory (DFT), and the couple-cluster (CCSD(T))
      method. From the obtained results, we analyse the impact of the electron
      correlation effects in these bimetallic clusters and find that the correlation of
      the valence electrons contributes significantly to the detachment energies and
      electron affinities, varying between 20% and 50% of their total values.
      Furthermore, we discuss the electron correlation effects on the stability of the
      clusters as well as the accuracy of the DFT and CCSD(T) calculations in the
      present systems. 

PMID- 24676471
TI  - LIM homeobox transcription factors, a novel subfamily which plays an important
      role in cancer (review).
AB  - LIM homeobox genes are one of the most important subfamilies of homeobox genes
      which encode LIM-homeodomain (LIM-HD) proteins featuring two LIM domains in their
      amino termini and a centrally located HD that is used to interact with specific
      DNA elements in target genes. Numerous studies have reported their fundamental
      roles in the development of various organisms; however, little is known about
      their functions in cancer. Recently, research has shown that LIM homeobox genes
      also play an important role in cancer development. Among 12 human LIM homeobox
      genes, 10 LIM-HD proteins have been reported to be associated with cancer. In the
      present review, we mainly summarize the functions of these genes in various types
      of cancer and their potential as biomarkers and the related challenges. More in
      depth research concerning LIM homeobox genes in cancer from a signaling pathway
      perspective may help to understand tumor profiles, establish biomarkers and guide
      choices for combinatorial drug therapies. 

PMID- 24676469
TI  - Genetic variants underlying risk of endometriosis: insights from meta-analysis of
      eight genome-wide association and replication datasets.
AB  - BACKGROUND: Endometriosis is a heritable common gynaecological condition
      influenced by multiple genetic and environmental factors. Genome-wide association
      studies (GWASs) have proved successful in identifying common genetic variants of
      moderate effects for various complex diseases. To date, eight GWAS and
      replication studies from multiple populations have been published on
      endometriosis. In this review, we investigate the consistency and heterogeneity
      of the results across all the studies and their implications for an improved
      understanding of the aetiology of the condition. METHODS: Meta-analyses were
      conducted on four GWASs and four replication studies including a total of 11 506
      cases and 32 678 controls, and on the subset of studies that investigated
      associations for revised American Fertility Society (rAFS) Stage III/IV including
      2859 cases. The datasets included 9039 cases and 27 343 controls of European
      (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese
      ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity
      statistics (Cochran's Q test), were used to investigate the evidence of the nine
      reported genome-wide significant loci across datasets and populations. RESULTS:
      Meta-analysis showed that seven out of nine loci had consistent directions of
      effect across studies and populations, and six out of nine remained genome-wide
      significant (P < 5 * 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 * 10(-9)),
      rs7521902 near WNT4 (P = 1.8 * 10(-15)), rs10859871 near VEZT (P = 4.7 * 10(
      15)), rs1537377 near CDKN2B-AS1 (P = 1.5 * 10(-8)), rs7739264 near ID4 (P = 6.2 *
      10(-10)) and rs13394619 in GREB1 (P = 4.5 * 10(-8)). In addition to the six loci,
      two showed borderline genome-wide significant associations with Stage III/IV
      endometriosis, including rs1250248 in FN1 (P = 8 * 10(-8)) and rs4141819 on 2p14
      (P = 9.2 * 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on
      chromosome 2, showed significant evidence of heterogeneity across datasets (P <
      0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV
      cases, implying that they are likely to be implicated in the development of
      moderate to severe, or ovarian, disease. While three out of nine loci were inter
      genic, the remaining were in or near genes with known functions of biological
      relevance to endometriosis, varying from roles in developmental pathways to
      cellular growth/carcinogenesis. CONCLUSIONS: Our meta-analysis shows remarkable
      consistency in endometriosis GWAS results across studies, with little evidence of
      population-based heterogeneity. They also show that the phenotypic
      classifications used in GWAS to date have been limited. Stronger associations
      with Stage III/IV disease observed for most loci emphasize the importance for
      future studies to include detailed sub-phenotype information. Functional studies
      in relevant tissues are needed to understand the effect of the variants on
      downstream biological pathways.

PMID- 24676472
TI  - Development and validation of a genotype 3 recombinant protein-based immunoassay
      for hepatitis E virus serology in swine.
AB  - Hepatitis E virus (HEV) is classified within the family Hepeviridae, genus
      Hepevirus. HEV genotype 3 (Gt3) infections are endemic in pigs in Western Europe
      and in North and South America and cause zoonotic infections in humans. Several
      serological assays to detect HEV antibodies in pigs have been developed, at first
      mainly based on HEV genotype 1 (Gt1) antigens. To develop a sensitive HEV Gt3
      ELISA, a recombinant baculovirus expression product of HEV Gt3 open reading frame
      2 was produced and coated onto polystyrene ELISA plates. After incubation of
      porcine sera, bound HEV antibodies were detected with anti-porcine anti-IgG and
      anti-IgM conjugates. For primary estimation of sensitivity and specificity of the
      assay, sets of sera were used from pigs experimentally infected with HEV Gt3. For
      further validation of the assay and to set the cutoff value, a batch of 1100 pig
      sera was used. All pig sera were tested using the developed HEV Gt3 assay and two
      other serologic assays based on HEV Gt1 antigens. Since there is no gold standard
      available for HEV antibody testing, further validation and a definite setting of
      the cutoff of the developed HEV Gt3 assay were performed using a statistical
      approach based on Bayes' theorem. The developed and validated HEV antibody assay
      showed effective detection of HEV-specific antibodies. This assay can contribute
      to an improved detection of HEV antibodies and enable more reliable estimates of
      the prevalence of HEV Gt3 in swine in different regions. 

PMID- 24676473
TI  - Acute effect of alcohol intake on sine-wave Cartesian and polar contrast
      sensitivity functions.
AB  - The aim of this study was to assess contrast sensitivity for angular frequency
      stimuli as well as for sine-wave gratings in adults under the effect of acute
      ingestion of alcohol. We measured the contrast sensitivity function (CSF) for
      gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle
      (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96
      cycles/360 degrees . Twenty adults free of ocular diseases, with normal or
      corrected-to-normal visual acuity, and no history of alcoholism were enrolled in
      two experimental groups: 1) no alcohol intake (control group) and 2) alcohol
      ingestion (experimental group). The average concentration of alcohol in the
      experimental group was set to about 0.08%. We used a paradigm involving a forced
      choice method. Maximum sensitivity to contrast for sine-wave gratings in the two
      groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360 degrees 
      for angular frequency stimuli. Significant changes in contrast sensitivity were
      observed after alcohol intake compared with the control condition at spatial
      frequency of 4 cpd and 1, 24, and 48 cycles/360 degrees  for angular frequency
      stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at
      maximum sensitivity and at the low and high frequency ends for angular frequency
      stimuli, both under photopic luminance conditions. 

PMID- 24676474
TI  - Effects of eugenol on resting tension of rat atria.
AB  - In cardiac and skeletal muscle, eugenol (MUM range) blocks excitation-contraction
      coupling. In skeletal muscle, however, larger doses of eugenol (mM range) induce
      calcium release from the sarcoplasmic reticulum. The effects of eugenol are
      therefore dependent on its concentration. In this study, we evaluated the effects
      of eugenol on the contractility of isolated, quiescent atrial trabeculae from
      male Wistar rats (250-300 g; n=131) and measured atrial ATP content. Eugenol (1,
      3, 5, 7, and 10 mM) increased resting tension in a dose-dependent manner.
      Ryanodine [100 uM; a specific ryanodine receptor (RyR) blocker] and procaine (30
      mM; a nonspecific RyR blocker) did not block the increased resting tension
      induced by eugenol regardless of whether extracellular calcium was present. The
      myosin-specific inhibitor 2,3-butanedione monoxime (BDM), however, reversed the
      increase in resting tension induced by eugenol. In Triton-skinned atrial
      trabeculae, in which all membranes were solubilized, eugenol did not change
      resting tension, maximum force produced, or the force vs pCa relationship (pCa=
      log [Ca2+]). Given that eugenol reduced ATP concentration, the increase in
      resting tension observed in this study may have resulted from cooperative
      activation of cardiac thin filaments by strongly attached cross-bridges (rigor
      state). 

PMID- 24676475
TI  - CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model
      in vivo.
AB  - Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to
      multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the
      potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for
      drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug
      resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to
      knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that
      lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and
      significantly inhibit tumor growth when combined with chemotherapy in vivo.
      Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein
      expression were efficiently downregulated, and P53 was upregulated, after RNAi.
      Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1
      is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may
      participate in MDR of breast cancer by regulating P-glycoprotein and P53
      expression. 

PMID- 24676476
TI  - Leukocytosis, muscle damage and increased lymphocyte proliferative response after
      an adventure sprint race.
AB  - The effect of an adventure sprint race (ASR) on T-cell proliferation, leukocyte
      count and muscle damage was evaluated. Seven young male runners completed an ASR
      in the region of Serra do Espinhaco, Brazil. The race induced a strong
      leukocytosis (6.22+/-2.04*10(3) cells/mm3 before vs 14.81+/-3.53*10(3) cells/mm3
      after the race), marked by a significant increase of neutrophils and monocytes
      (P<0.05), but not total lymphocytes, CD3+ CD4+ or CD3+ CD8+ cells. However, the T
      cell proliferative response to mitogenic stimulation was increased (P=0.025)
      after the race, which contradicted our hypothesis that ASR, as a high-demand
      competition, would inhibit T-cell proliferation. A positive correlation (P=0.03,
      r=0.79) was observed between the proliferative response of lymphocytes after the
      race and the time to complete the race, suggesting that the proliferative
      response was dependent on exercise intensity. Muscle damage was evident after the
      race by increased serum levels of aspartate amino transferase (24.99+/-8.30 vs
      50.61+/-15.76 U/L, P=0.003). The results suggest that humoral factors and
      substances released by damaged muscle may be responsible for lymphocyte
      activation, which may be involved in muscle recovery and repair.

PMID- 24676477
TI  - The use of amphipols for solution NMR studies of membrane proteins: advantages
      and constraints as compared to other solubilizing media.
AB  - Solution-state nuclear magnetic resonance studies of membrane proteins are
      facilitated by the increased stability that trapping with amphipols confers to
      most of them as compared to detergent solutions. They have yielded information on
      the state of folding of the proteins, their areas of contact with the polymer,
      their dynamics, water accessibility, and the structure of protein-bound ligands.
      They benefit from the diversification of amphipol chemical structures and the
      availability of deuterated amphipols. The advantages and constraints of working
      with amphipols are discussed and compared to those associated with other non
      conventional environments, such as bicelles and nanodiscs. 

PMID- 24676479
TI  - Using auxiliary information to improve wildlife disease surveillance when
      infected animals are not detected: a Bayesian approach.
AB  - There are numerous situations in which it is important to determine whether a
      particular disease of interest is present in a free-ranging wildlife population.
      However adequate disease surveillance can be labor-intensive and expensive and
      thus there is substantial motivation to conduct it as efficiently as possible.
      Surveillance is often based on the assumption of a simple random sample, but this
      can almost always be improved upon if there is auxiliary information available
      about disease risk factors. We present a Bayesian approach to disease
      surveillance when auxiliary risk information is available which will usually
      allow for substantial improvements over simple random sampling. Others have
      employed risk weights in surveillance, but this can result in overly optimistic
      statements regarding freedom from disease due to not accounting for the
      uncertainty in the auxiliary information; our approach remedies this. We compare
      our Bayesian approach to a published example of risk weights applied to chronic
      wasting disease in deer in Colorado, and we also present calculations to examine
      when uncertainty in the auxiliary information has a serious impact on the risk
      weights approach. Our approach allows "apples-to-apples" comparisons of
      surveillance efficiencies between units where heterogeneous samples were
      collected. 

PMID- 24676478
TI  - Role for the TRPV1 channel in insulin secretion from pancreatic beta cells.
AB  - Transient receptor potential channels have been put forward as regulators of
      insulin secretion. A role for the TRPV1 ion channel in insulin secretion has been
      suggested in pancreatic beta cell lines. We explored whether TRPV1 is
      functionally expressed in RINm5F and primary beta cells from neonate and adult
      rats. We examined if capsaicin could activate cationic non-selective currents.
      Our results show that TRPV1 channels are not functional in insulin-secreting
      cells, since capsaicin did not produce current activation, not even under culture
      conditions known to induce the expression of other ion channels in these cells.
      Although TRPV1 channels seem to be irrelevant for the physiology of isolated beta
      cells, they may play a role in glucose homeostasis acting through the nerve
      fibers that regulate islet function. At the physiological level, we observed that
      Trpv1 (-/-) mice presented lower fasting insulin levels than their wild-type
      littermates, however, we did not find differences between these experimental
      groups nor in the glucose tolerance test or in the insulin secretion. However, we
      did find that the Trpv1 (-/-) mice exhibited a higher insulin sensitivity
      compared to their wild-type counterparts. Our results demonstrate that TRPV1 does
      not contribute to glucose-induced insulin secretion in beta cells as was
      previously thought, but it is possible that it may control insulin sensitivity. 

PMID- 24676482
TI  - Association of panic disorder with quality of life among individuals with
      headache.
AB  - OBJECTIVE: To study the association of panic disorder with severity of anxiety
      symptoms and quality of life among individuals presenting with headache. METHODS:
      This was a single-centre, cross-sectional, observational, questionnaire-based
      study performed at the psychiatry outpatient department of a tertiary care
      hospital. Participants of both genders, aged between 18 and 60 years, and having
      headache as a presenting complaint for at least 3 months were evaluated for
      symptoms of panic disorder. The severity of headache was evaluated with the
      visual analogue scale and that of anxiety disorder with the Hamilton Anxiety
      Rating Scale (HAM-A). The quality of life was evaluated with the World Health
      Organization Quality of Life Scale brief version. Proportions of participants
      were compared using Chi-square test, and scores by Mann-Whitney test or Kruskal
      Wallis test followed by Dunn's post-hoc multiple comparisons. RESULTS: The
      frequency of panic disorder among patients with headache was 67%. Those with
      daily headache and panic disorder (with or without agoraphobia) showed higher HAM
      A score and poorer quality of life than those with intermittent headache and
      without panic disorder, respectively. CONCLUSIONS: Co-morbid panic disorder among
      patients with headache was associated with high anxiety score and poor quality of
      life.

PMID- 24676480
TI  - Integrating de novo transcriptome assembly and cloning to obtain chicken
      Ovocleidin-17 full-length cDNA.
AB  - Efficiently obtaining full-length cDNA for a target gene is the key step for
      functional studies and probing genetic variations. However, almost all sequenced
      domestic animal genomes are not 'finished'. Many functionally important genes are
      located in these gapped regions. It can be difficult to obtain full-length cDNA
      for which only partial amino acid/EST sequences exist. In this study we report a
      general pipeline to obtain full-length cDNA, and illustrate this approach for one
      important gene (Ovocleidin-17, OC-17) that is associated with chicken eggshell
      biomineralization. Chicken OC-17 is one of the best candidates to control and
      regulate the deposition of calcium carbonate in the calcified eggshell layer. OC
      17 protein has been purified, sequenced, and has had its three-dimensional
      structure solved. However, researchers still cannot conduct OC-17 mRNA related
      studies because the mRNA sequence is unknown and the gene is absent from the
      current chicken genome. We used RNA-Seq to obtain the entire transcriptome of the
      adult hen uterus, and then conducted de novo transcriptome assembling with
      bioinformatics analysis to obtain candidate OC-17 transcripts. Based on this
      sequence, we used RACE and PCR cloning methods to successfully obtain the full
      length OC-17 cDNA. Temporal and spatial OC-17 mRNA expression analyses were also
      performed to demonstrate that OC-17 is predominantly expressed in the adult hen
      uterus during the laying cycle and barely at immature developmental stages.
      Differential uterine expression of OC-17 was observed in hens laying eggs with
      weak versus strong eggshell, confirming its important role in the regulation of
      eggshell mineralization and providing a new tool for genetic selection for
      eggshell quality parameters. This study is the first one to report the full
      length OC-17 cDNA sequence, and builds a foundation for OC-17 mRNA related
      studies. We provide a general method for biologists experiencing difficulty in
      obtaining candidate gene full-length cDNA sequences. 

PMID- 24676481
TI  - Translation and validation of the Chinese version of the short Warwick-Edinburgh
      Mental Well-being Scale for patients with mental illness in Hong Kong.
AB  - OBJECTIVE: Quality of life outcomes are useful in the assessment of mental and
      social wellbeing and for informed health care decision-making, especially in the
      choice of interventions in psychiatric rehabilitation. In its original form, the
      Warwick-Edinburgh Mental Well-being Scale (WEMWBS) is a proven reliable and valid
      tool for assessing quality of life in normal adults, but not in adults from Asian
      countries. A shortened 7-item version of WEMWBS (SWEMWBS) with good internal
      construct validity was used for this study. The present study describes the
      translation of WEMWBS from English to Chinese and its validation in a sample of
      Chinese-speaking patient population. METHODS: Participants included patients
      admitted to the inpatient units, and those attending the day hospital and
      outpatient units of the Kowloon Hospital (n = 126). Translation was performed
      using the multiple forward and backward translation protocol. Patients also
      completed the 5-item World Health Organization Well-being Index (WHO5)
      questionnaire. A case therapist completed the Brief Psychiatric Rating Scale
      within 2 days. A total of 20 patients were selected for test-retest measurements
      performed after 2 weeks. RESULTS: The sample displayed a normal distribution of
      the Chinese version of SWEMWBS (C-SWEMWBS) scores (mean +/- standard deviation,
      23.16 +/- 5.39; skewness, -0.068; kurtosis, -0.355). Internal reliability
      coefficient (Cronbach's alpha) for C-SWEMWBS was 0.89 which was consistent with
      that of English version. The corrected item-total correlation was high with
      Spearman's rank correlation coefficients ranging from 0.57 (item 6) to 0.75 (item
      5). Good test-retest reliability was observed (r = 0.677; p = 0.001). Principal
      components factor analysis identified a single component (eigenvalues, 4.28;
      61.1% variance), similar to the English version. Scores of C-SWEMWBS were
      positively correlated with the scores of WHO5 (r = 0.49; p < 0.001), suggesting
      good concurrent validity. Few item scores including 'feeling useful', 'dealing
      with problems well', 'able to make decisions', and the total score were
      significantly correlated with diagnostic groups (p < 0.05). Education and
      diagnosis of mental illness were valid predictors for C-SWEMWBS (F = 5.41; p =
      0.01). There were no effects due to age and gender. CONCLUSION: The C-SWEMWBS
      showed high levels of internal consistency and reliability against accepted
      criteria. It is short, acceptable, and culturally meaningful to clients with
      mental illness. Further large-scale studies in normal subjects and varied patient
      groups are recommended to generalise the findings.

PMID- 24676483
TI  - Comparative study on attitudes and psychological problems of mothers towards
      their children with developmental disability.
AB  - OBJECTIVE: Parents' positive attitudes and psychological wellbeing play an
      important role in the development of the children with developmental disability.
      This study aimed to measure the prevalence of psychological problems among
      mothers of children with autism disorder, intellectual disability, and Down
      syndrome. The second aim was to assess the differences in mothers' attitudes and
      psychological problems among their children with intellectual disability, autism
      disorder, and Down syndrome. The third aim was to identify whether negative
      attitude was a predictor of psychological problems in these mothers. METHODS: In
      this study, 112 mothers of children having mild and moderate levels of autism
      disorder, Down syndrome, and intellectual disability were assessed using the
      Parental Attitude Scale and General Health Questionnaire-28. RESULTS: Overall,
      mothers of children with intellectual disability were found to have the most
      negative attitude towards their child. Mothers of children with autism disorder
      exhibited higher scores on somatic symptoms, anxiety, and social dysfunction when
      compared with their counterparts with Down syndrome and intellectual disability.
      Negative attitude was a significant predictor of psychological problems.
      CONCLUSION: Parental attitudes and psychological problems would vary among
      mothers of children with different types of developmental disability.

PMID- 24676484
TI  - A thai version of mindfulness questionnaire: Srithanya Sati scale.
AB  - OBJECTIVE: To develop a scale for assessing mindfulness named Srithanya Sati
      Scale (SSS) in Thai context. METHODS: Fourteen items were derived with the help
      from meditation experts. These were then validated by 16 mental health experts
      followed by analysis of their psychometric properties. A total of 466 subjects
      were purposively sampled from various sources. The construct validity of the
      scale was examined by confirmatory factor analysis. The hierarchical model was
      applied to test whether 3-factor model of SSS could adequately explain overall
      mindfulness. Test-retest reliability and the internal consistency of each
      subscale (awareness, acceptance, and self-recollection) were analysed by
      Pearson's correlation coefficient and Cronbach's alpha, respectively. Srithanya
      Stress Test was applied to test the discriminant validity of the questionnaire.
      The Philadelphia Mindfulness Scale was used for testing the concurrent validity.
      RESULTS: The 11-item SSS was found to fit across groups of people with different
      meditation experiences. Two of the components (awareness and self-recollection)
      explained the overall mindfulness in beginners. The reliability and other
      psychometric properties of the scale were highly acceptable. CONCLUSION: The SSS
      may be a reliable, valid, and acceptable tool for measuring mindfulness in the
      Thai population. Further studies are warranted in people with more experience in
      meditation, as well as clinical populations.

PMID- 24676486
TI  - Outcomes of SARS survivors in China: not only physical and psychiatric co
      morbidities.
AB  - The year 2013 marks the 10th anniversary of the outbreak of the severe acute
      respiratory syndrome (SARS). We present a comprehensive introduction to the
      current situation of surviving SARS victims in China where the disease originated
      and spread across the world 10 years ago. 

PMID- 24676485
TI  - The Hong Kong mental morbidity survey: background and study design.
AB  - Mental disorders are highly prevalent conditions with immense disease burden. To
      inform health and social services policy formulation, local psychiatric
      epidemiological data are required. The Hong Kong Mental Morbidity Survey is a 3
      year population-based study in which 5700 community-dwelling Chinese adults aged
      between 16 and 75 years were interviewed with the aim of evaluating the
      prevalence, co-morbidity, functional impairment, physical morbidity, and social
      determinants of significant mental disorders in the population. This paper
      describes the background and design of the survey, and is the first territory
      wide psychiatric epidemiological study in Hong Kong. 

PMID- 24676487
TI  - Increasing the activity and enantioselectivity of lipases by sol-gel
      immobilization: further advancements of practical interest.
AB  - The entrapment of lipases in hydrophobic silicate matrices formed by sol-gel
      mediated hydrolysis of RSi(OCH3)3/Si(OCH3)4 as originally reported in 1996 has
      been improved over the years by a number of modifications. In the production of
      second-generation sol-gel lipase immobilizates, a variety of additives during the
      sol-gel process leads to increased activity and enhanced stereoselectivity in
      esterifying kinetic resolution. Recent advances in this type of lipase
      immobilization are reviewed here, in addition to new results regarding the sol
      gel entrapment of the lipase from Burkholderia cepacia. It constitutes an
      excellent heterogeneous biocatalyst in the acylating kinetic resolution of two
      synthetically and industrially important chiral alcohols, rac-sulcatol and rac
      trans-2-methoxycyclohexanol. The observation that the catalyst can be used 10
      times in recycling experiments without losing its significant activity or
      enantioselectivity demonstrates the practical viability of the sol-gel approach. 

PMID- 24676488
TI  - Aneurysmal wall enhancement and perianeurysmal edema after endovascular treatment
      of unruptured cerebral aneurysms.
AB  - INTRODUCTION: Perianeurysmal edema and aneurysm wall enhancement are previously
      described phenomenon after coil embolization attributed to inflammatory reaction.
      We aimed to demonstrate the prevalence and natural course of these phenomena in
      unruptured aneurysms after endovascular treatment and to identify factors that
      contributed to their development. METHODS: We performed a retrospective analysis
      of consecutively treated unruptured aneurysms between January 2000 and December
      2011. The presence and evolution of wall enhancement and perianeurysmal edema on
      MRI after endovascular treatment were analyzed. Variable factors were compared
      among aneurysms with and without edema. RESULTS: One hundred thirty-two
      unruptured aneurysms in 124 patients underwent endovascular treatment. Eighty
      five (64.4 %) aneurysms had wall enhancement, and 9 (6.8 %) aneurysms had
      perianeurysmal brain edema. Wall enhancement tends to persist for years with two
      patterns identified. Larger aneurysms and brain-embedded aneurysms were
      significantly associated with wall enhancement. In all edema cases, the aneurysms
      were embedded within the brain and had wall enhancement. Progressive thickening
      of wall enhancement was significantly associated with edema. Edema can be
      symptomatic when in eloquent brain and stabilizes or resolves over the years.
      CONCLUSIONS: Our study demonstrates the prevalence and some appreciation of the
      natural history of aneurysmal wall enhancement and perianeurysmal brain edema
      following endovascular treatment of unruptured aneurysms. Aneurysmal wall
      enhancement is a common phenomenon while perianeurysmal edema is rare. These
      phenomena are likely related to the presence of inflammatory reaction near the
      aneurysmal wall. Both phenomena are usually asymptomatic and self-limited, and
      prophylactic treatment is not recommended.

PMID- 24676489
TI  - Perspectives on the therapeutic modulation of an alternative cell death,
      programmed necrosis (review).
AB  - In response to overwhelming external stimuli, cells are forced to die in
      different ways. By default, cells are prone to apoptosis, a programmed cell death
      through the activation of the caspase cascade. However, this process would be
      blocked if one of the proteins involved in executing apoptosis was genetically
      impaired or chemically inhibited, or if the apoptotic machinery was not properly
      operated under specific conditions, such as ischemia and microbial infection. To
      address these issues, the paradigm of programmed cell death needs to be revised;
      thus, an alternative form of cell death, programmed necrosis (termed necroptosis,
      through the caspase-independent pathway), which is distinct from apoptosis in
      many aspects, has recently been adopted. There is much interest in programmed
      necrosis as it is very closely associated with pathophysiological conditions,
      such as stroke, heart attack and septic shock. In an effort to identify target
      molecules of small compounds interfering with the signaling downstream of tumor
      necrosis factor-alpha (TNF-alpha), necrostatin-1 (Nec-1) was first identified to
      be a selective allosteric inhibitor of the death domain receptor-associated
      adaptor kinase, receptor interacting protein 1 (RIP1) in vitro. Since then, some
      novel scaffolds with selective and distinctive activity have been proposed. In
      this review, the significant advancement and state-of-art direction for the
      development of small molecules that can control programmed necrosis is discussed.
      Furthermore, the perspectives on novel strategies harnessing therapeutic targets
      identified thus far, are also discussed.

PMID- 24676490
TI  - Social support and the 'left behind' elderly in rural China: a case study from
      Jiangxi Province.
AB  - This study examines the living situation of elderly people in rural China whose
      children have left to work in other areas [the 'left behind' elderly (LBE)] and
      explores policy implications associated with their care. Based on survey data and
      interviews conducted in three villages in Jiangxi Province, China, we compare the
      living situation of the LBE and the 'non-left behind' elderly (NLBE). The data
      reveal that the LBE are relatively more isolated and that they spend less time
      interacting with neighbors and more time watching television. The study shows
      that the LBE have a much greater need for care services than income maintenance.
      Also, the LBE group has less social capital than the NLBE group. Based on our
      findings, it is clear that the proposal to use social capital and informal care
      cannot effectively meet all the needs of the LBE group. Instead, it is
      recommended that a comprehensive system of social support is developed. 

PMID- 24676491
TI  - Tobacco use among fourth year Bachelor of Science in Public Health (BSPH)
      students of the College of Public Health: University of the Philippines Manila,
      academic year 2012-2013.
AB  - This study determines the prevalence of tobacco use among graduating Public
      Health students at the College of Public Health, University of the Philippines
      Manila. It also describes the exposure to environmental tobacco smoke, attitudes,
      behaviors and smoking cessation training of students. This study used a
      descriptive cross-sectional study design, adapting a standard questionnaire,
      pretested and administered to 52 Bachelor of Science in Public Health (BSPH)
      students at the College of Public Health, University of the Philippines Manila.
      Data generated from the survey were encoded using Epi Info version 3.5.4 and
      analyzed using Stata version 12. The prevalence of smoking among 4th year BSPH
      students was 5.8 % (current smokers). In the past 7 days, respondents have been
      exposed to secondhand smoke (44 % where they live; 79 % in places other than
      where they live). Majority were aware of the official policy on smoking ban in
      school, however, 80 % said that the policy is not enforced. Majority had
      favorable attitudes in terms of banning tobacco sales to adolescents, banning
      advertising of tobacco products, banning smoking in restaurants, discos/bars/pubs
      and enclosed public places. Majority of the respondents also believed that health
      professionals should get specific training on cessation techniques, that they do
      serve as role models, and that they have a role in giving advice about smoking
      cessation. More than three-quarters (76.9 %) of students said that health
      professionals who smoke are less likely to advise patients to quit. Most of the
      graduating students learned about the dangers of smoking, importance of obtaining
      tobacco use history, and providing educational support materials in their public
      health education but only a few received formal training about smoking cessation
      approaches. The implementation of the no-smoking policy of the university must be
      revisited. Smoking cessation approaches should be incorporated in the public
      health curriculum and the role of public health students in advocating a smoke
      free lifestyle should be emphasized.

PMID- 24676492
TI  - New concepts in white adipose tissue physiology.
AB  - Numerous studies address the physiology of adipose tissue (AT). The interest
      surrounding the physiology of AT is primarily the result of the epidemic outburst
      of obesity in various contemporary societies. Briefly, the two primary metabolic
      activities of white AT include lipogenesis and lipolysis. Throughout the last two
      decades, a new model of AT physiology has emerged. Although AT was considered to
      be primarily an abundant energy source, it is currently considered to be a
      prolific producer of biologically active substances, and, consequently, is now
      recognized as an endocrine organ. In addition to leptin, other biologically
      active substances secreted by AT, generally classified as cytokines, include
      adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin,
      visfatin, and many others now collectively referred to as adipokines. The
      secretion of such biologically active substances by AT indicates its importance
      as a metabolic regulator. Cell turnover of AT has also recently been investigated
      in terms of its biological role in adipogenesis. Consequently, the objective of
      this review is to provide a comprehensive critical review of the current
      literature concerning the metabolic (lipolysis, lipogenesis) and endocrine
      actions of AT. 

PMID- 24676495
TI  - Cu(II)4L4 coordination-driven molecular container: a reusable visual colorimetric
      sensor for Ag(I) ions.
AB  - A Cu4L4 square-like molecular container which can be a reusable visual sensor for
      Ag(+) is reported. The present results can be a useful stepwise approach for the
      construction of the heterometallic supramolecular complexes with potential
      applications. 

PMID- 24676494
TI  - Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is
      dependent on elevated blood pressure.
AB  - Dietary salt intake has been linked to hypertension and cardiovascular disease.
      Accumulating evidence has indicated that salt-sensitive individuals on high salt
      intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal
      transition (EMT) participates in the development and progression of renal
      fibrosis in humans and animals. The objective of this study was to investigate
      the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty
      four male SS and consomic SS-13(BN) rats were randomized to a normal diet or a
      high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were
      analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was
      evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha
      smooth muscle actin (alpha-SMA). After 4 weeks, SBP and albuminuria were
      significantly increased in the SS high-salt group compared with the normal diet
      group. Dietary salt intake induced renal fibrosis and tubular EMT as identified
      by reduced expression of E-cadherin and enhanced expression of alpha-SMA in SS
      rats. Both blood pressure and renal interstitial fibrosis were negatively
      correlated with E-cadherin but positively correlated with alpha-SMA. Salt intake
      induced tubular EMT and renal injury in SS rats, and this relationship might
      depend on the increase in blood pressure.

PMID- 24676493
TI  - The role of oxytocin in cardiovascular regulation.
AB  - Studies of body volume expansion have indicated that lesions of the anteroventral
      third ventricle and median eminence block the release of atrial natriuretic
      peptide (ANP) into the circulation. Detailed analysis of the lesions showed that
      activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it
      has become clear that activation of neuronal circuitry elicits OT secretion into
      the circulation, activating atrial OT receptors and ANP release from the heart.
      Subsequently, we have uncovered the entire functional OT system in the rat and
      the human heart. An abundance of OT has been observed in the early development of
      the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been
      demonstrated in various types of stem cells. OT treatment of mesenchymal stem
      cells stimulates paracrine factors beneficial for cardioprotection.
      Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative
      inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv)
      vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii)
      metabolic effects. OT actions are mediated by nitric oxide and ANP. The
      beneficial actions of OT may include the increase in glucose uptake by CMs and
      stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial
      protection of several cell types. In experimentally induced myocardial infarction
      in rats, continuous in vivo OT delivery improves cardiac healing and cardiac
      work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti
      inflammatory and cardioprotective roles and improves vascular and metabolic
      functions, it demonstrates potential for therapeutic use in various pathologic
      conditions. 

PMID- 24676496
TI  - Determination of the shape and curvature of nonplanar lipid bilayers that are
      bent in a single plane in molecular dynamics simulations.
AB  - The curvature of biological membranes is known to be an important influence on
      important phenomena such as membrane fusion, endocytosis, and the functioning of
      integral membrane proteins. There is a growing demand for analytical tools that
      are able accommodate molecular dynamics trajectories of significantly curved
      lipid bilayers. In this work, an algorithm for determining the shape and
      curvature of a nonplanar lipid bilayer in molecular dynamics simulations is
      proposed. The algorithm calculates the coordinates of the midline and the
      curvature of the bilayer as well as the local normal to it at any point on the
      membrane, which is bent arbitrarily in a single plane and is topologically
      equivalent to an infinite bilayer. The algorithm is implemented as a C++ program
      and tested by exploring the molecular dynamic trajectories of a highly curved
      meander-like asymmetric lipid bilayer. The algorithm is general enough to allow
      it to be easily applied to other geometries of nonplanar membrane systems. 

PMID- 24676497
TI  - Roles of electrostatic interaction and dispersion in CH...CH, CH...pi, and
      pi...pi ethylene dimers.
AB  - Ab initio molecular orbital calculations were performed up to the CCSD(T)/CBS
      level to investigate the roles of the electrostatic interaction and dispersion in
      three basic types of intermolecular interaction, namely CH...CH, CH...pi, and
      pi...pi interactions, in D(2d), C(2v), and C(i) ethylene dimers, respectively.
      SAPT energy decomposition revealed that the electrostatic interaction is more
      significant than expected, with its value being close to that of the net
      interaction energy. Dispersion is the largest stabilizing force and it plays the
      main role in balancing out exchange repulsion. This balance is related to the
      proposed concept of "contact." The roles of the sigma and pi electrons were
      distinguished in the electrostatic interaction by performing distributed
      multipole analysis and in dispersion by performing frozen-orbital SAPT (fo-SAPT)
      calculations. The electrostatic part of the interaction energy for each ethylene
      dimer can be understood as either a quadrupole-quadrupole attraction or the
      attraction between C and H atoms. (Electron pair)-(electron pair) contributions
      to the dispersion were calculated by the fo-SAPT method to shed light on the
      nature of dispersion. In these dimers, contributions to the dispersion can arise
      from pi<->pi, sigma<->pi, or sigma<->sigma electron-pair interactions.
      Surprisingly, sigma<->pi interactions dominate the dispersion in all three
      ethylene dimers. The pi<->pi contribution is very small, even in the displaced
      parallel structure (C(i)). The sigma<->sigma interaction contributes to
      intermolecular binding by helping the dispersion to balance out exchange
      repulsion, but this interaction is limited to the most stable D(2d) structure,
      which is characterized by four pairs of close dihydrogen contacts. The concept of
      an electron-pair "contact" was introduced to describe the exchange-dispersion
      balance. The D(2d) dimer is stabilized by a large number of such contacts.

PMID- 24676498
TI  - Empty versus filled polyhedra: 11 vertex bare germanium clusters.
AB  - The structures and energetics of centered 10-vertex Ge@Ge10(z) (z = -4, -2, 0,
      +2, +4) clusters have been investigated by density functional theory (DFT) for
      comparison with the previously studied isomeric empty 11-vertex Ge11(z) clusters.
      For the cationic species (z = +2, +4) such centered Ge@Ge10(z) structures are
      shown to be energetically competitive (within ~1 kcal mol-1) to the lowest energy
      isomeric empty Ge11(z) structures. These Ge@Ge10(z) structures can be derived
      from the lowest energy empty 10-vertex Ge10(z-4) structures by inserting a Ge4+
      ion in the center. The outer 10-vertex polyhedron in the lowest energy Ge@Ge102+
      dication structure is the most spherical D(4d) bicapped square antiprism, which
      is also the lowest energy structure of the empty Ge102- dianion, as expected from
      the Wade-Mingos skeletal electron counting rules. For the tetracationic Ge114+
      /Ge@Ge104+ system the lowest energy centered Ge@Ge104+ structure can be obtained
      by inserting a Ge4+ ion in the center of a C(3v) deltahedral empty Ge10 cluster.
      Centered 10-vertex polyhedral Ge@Ge10(z) structures were also found for the
      neutral (z = 0) and dianionic (z = -2) systems but at significantly higher
      energies than the lowest energy isomeric empty Ge11(z) structures.

PMID- 24676499
TI  - Endo- and exocytic budding transformation of slow-diffusing membrane domains
      induced by Alzheimer's amyloid beta.
AB  - Cell-sized liposomes are a powerful tool for clarifying physicochemical
      mechanisms that govern molecular interactions. Herein, budding transformation of
      membrane domains was induced by amyloid beta peptides. The peptides increased the
      membrane viscosity as demonstrated by the Brownian motion of membrane domains.
      These results could aid in understanding the physicochemical mechanism of
      Alzheimer's disease. 

PMID- 24676500
TI  - Repeated lipopolysaccharide stimulation promotes cellular senescence in human
      dental pulp stem cells (DPSCs).
AB  - Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell (MSC)
      characterized by multi-lineage differentiation making it an attractive choice for
      tissue regeneration. However, before DPSCs can be used for cell-based therapy, we
      have to understand their biological properties in response to intrinsic and
      extrinsic stimuli such as lipopolysaccharide (LPS). DPSCs were therefore
      stimulated with LPS and senescence was evaluated by senescence-associated beta
      galactosidase (SA-beta-gal) staining, with cell number and cell-cycle arrest
      being examined by BrdU assay and flow cytometry, respectively. The morphology of
      DPSCs was characterized by their flat shape, increased size and increased SA-beta
      gal activity after repeated stimulation (3 or 6 times) with LPS. Reactive oxygen
      species (ROS) staining showed that the number of ROS-stained cells and the DCFH
      fluorescent level were higher in the LPS-treated DPSCs compared with those in the
      untreated DPSCs. Protein and mRNA expression levels of gamma-H2A.X and p16(INK4A)
      were also increased in DPSCs with repeated LPS stimulation. We found that the LPS
      bound with Toll-like receptor 4 (TLR4) and that TLR4 signaling accounted for
      p16(INK4A) expression. Further results indicated that the senescence of DPSCs
      stimulated repeatedly with LPS was reversed by p16(INK4A) short interfering RNA.
      The DNA damage response and p16(INK4A) pathways might be the main mediators of
      DPSC senescence induced by repeated LPS stimulation. Thus, DPSCs tend to undergo
      senescence after repeated activation, implying that DPSC senescence starts after
      many inflammatory challenges. Ultimately, these findings should lead to a better
      understanding of DPSC-based clinical therapy.

PMID- 24676502
TI  - A copper based pillared-bilayer metal organic framework: its synthesis, sorption
      properties and catalytic performance.
AB  - A new 2D pillared-bilayer flexible open metal organic framework
      {[Cu(tdc)(bpe)]n.2n(H2O).n(MeOH)} (compound 1) [H2tdc = 2,5 thiophenedicarboxylic
      acid; bpe = 1,2-bis(4-pyridyl)ethane] has been synthesized through a solvent
      diffusion technique and structurally characterized. The structure analysis
      reveals that the tdc ligands formed bilayers with the Cu(II) ions along the b
      direction and the layers are further pillared by bpe linkers and resulted in a 2D
      pillared-bilayer porous framework with a four connected uninodal sq1/Shubnikob
      tetragonal plane net with the Schalfli symbol {4(4).6(2)}. The framework is
      enclosed with large square shaped channels (13.7 * 8.35 A(2)) along the bc-plane
      and the channels are occupied by guest solvent molecules. The adsorption studies
      reveal that compound 1 shows selective adsorption for CO2 over CH4 at room
      temperature and it also shows hysteretic sorption for a few protic solvents (H2O
      and EtOH) and a Type-1 isotherm for an aprotic solvent (CH3CN). The catalytic
      performance of compound 1 for Glaser type homo-coupling reactions has also been
      reported.

PMID- 24676501
TI  - Model of the distribution of diastolic left ventricular posterior wall thickness
      in healthy adults and its impact on the behavior of a string of virtual
      cardiomyocytes.
AB  - Correlation of the thickness of the left ventricular posterior wall (LVPWd) with
      various parameters, including age, gender, weight and height, was investigated in
      this study using regression models. Multicenter derived database comprised over
      4,000 healthy individuals. The developed models were further utilized in the in
      vitro-in vivo (IVIV) translation of the drug cardiac safety data with use of the
      mathematical model of human cardiomyocytes operating at the virtual healthy
      population level. LVPWd was assumed to be equivalent to the length of one
      dimensional string of virtual cardiomyocyte cells which was presented, as other
      physiological factors, to be a parameter influencing the simulated pseudo-ECG
      (pseudoelectrocardiogram), QTcF and ?QTcF, both native and modified by exemplar
      drug (disopyramide) after I Kr current disruption. Simulation results support
      positive correlation between the LVPWd and QTcF/?QTc. Developed models allow more
      detailed description of the virtual population and thus inter-individual
      variability influence on the drug cardiac safety. 

PMID- 24676503
TI  - Catheter tract metastasis associated with indwelling pleural catheters.
AB  - BACKGROUND: Indwelling pleural catheters (IPCs) are commonly used to manage
      malignant effusions. Tumor spread along the catheter tract remains a clinical
      concern for which limited data exist. We report the largest series of IPC-related
      catheter tract metastases (CTMs) to date, to our knowledge. METHODS: This is a
      single-center, retrospective review of IPCs inserted over a 44-month period. CTM
      was defined as a new, solid chest wall lesion over the IPC insertion site and/or
      the tunneled subcutaneous tract that was clinically compatible with a malignant
      tract metastasis. RESULTS: One hundred ten IPCs were placed in 107 patients
      (76.6% men; 60% with mesothelioma). CTM developed in 11 cases (10%): nine with
      malignant pleural mesothelioma and two with metastatic adenocarcinoma. CTM often
      developed late (median, 280 days; range, 56-693) post-IPC insertion. Seven cases
      had chest wall pain, and six received palliative radiotherapy to the CTM.
      Radiotherapy was well tolerated, with no major complications and causing no
      damage to the catheters. Longer interval after IPC insertion was the sole
      significant risk factor for development of CTM (OR, 2.495; 95% CI, 1.247-4.993; P
      = .0098) in the multivariate analyses. CONCLUSIONS: IPC-related CTM is uncommon
      but can complicate both mesothelioma and metastatic carcinomas. The duration of
      interval after IPC insertion is the key risk factor identified for development of
      CTM. Symptoms are generally mild and respond well to radiotherapy, which can be
      administered safely without removal of the catheter.

PMID- 24676504
TI  - Preventing adolescent pregnancy: biological, social, cultural, and political
      influences on age at first sexual intercourse.
AB  - Age at first sexual intercourse (AFSI) is the initial factor related to
      adolescents' sexual life that may increase the risk of adolescent pregnancy. We
      explored the biological, social, cultural, and political predictors of AFSI
      addressing several gaps that prevent us from generalizing the results of past
      research to adolescent pregnancy prevention. We also explored the moderating
      effects of cultural variables on the links between social and political
      predictors and AFSI. Our sample consisted of 889 Portuguese female adolescents
      aged 12-19. Earlier age at menarche, non-intact family structure, maternal
      history of adolescent pregnancy, lower maternal emotional warmth, absence of
      religious involvement, and living in Portugal's mainland and in a legal context
      penalizing abortion predicted earlier AFSI. School attendance predicted earlier
      AFSI among adolescents of European ethnic origin; adolescents of non-European
      ethnic origin presented the opposite, but non-significant, pattern. These
      findings suggest that, in addition to isolated characteristics, factors from
      different ecological contexts should be considered when planning interventions
      designed to foster healthy and informed transitions to sexual initiation and
      prevent the related risks of unwanted outcomes. We discuss implications for
      future research and practice. 

PMID- 24676505
TI  - Copper toxicity to Phaeodactylum tricornutum: a survey of the sensitivity of
      various toxicity endpoints at the physiological, biochemical, molecular and
      structural levels.
AB  - Copper (Cu) is one of the most toxic metals in phytoplankton but the toxicity
      mechanisms of this metal are still not fully understood. This study examines the
      toxicity targets of Cu in the modeled marine diatom, Phaeodactylum tricornutum,
      at the physiological (cell division, DNA cell cycle), biochemical [pigments
      synthesis, reactive oxygen species (ROS) and malondialdehyde (MDA)], structural
      (subcellular observation by flow cytometry) and molecular (transcription of
      several metalloprotein genes) level. Cu toxicity was detectable at all these
      levels after 48 h of exposure to >=20 MUM total initial added Cu. The order of
      sensitivity of all the studied Cu toxicity endpoints was: G2/M phase > MDA >
      metalloproteins RNA of the photosynthetic electron transport chain (ETC) >
      metalloproteins RNA of the respiratory chains > G0/G1 phase > pigments ~ S phase
      > propidium iodide > estimated cell yield > ROS. The relatively sensitive
      decrease of the transcription of metalloproteins RNA of the ETC in response to Cu
      exposure, if associated to an effective decrease in the expression of the
      proteins composing the ETC, may help to initially mitigate the ROS-mediated toxic
      effects of Cu in P. tricornutum. However, this cellular response to Cu was only
      transitory and the transcription of virtually all genes involved in redox
      electron transfer chains was up-regulated within an interval of 2 days. This
      study brings new insights into the cellular mechanisms of Cu toxicity by
      documenting the sensitivity and kinetics of multiple Cu-cellular targets in one
      marine alga.

PMID- 24676506
TI  - Transanal endoscopic microsurgery with 3-D (TEM) or high-definition 2-D transanal
      endoscopic operation (TEO) for rectal tumors. A prospective, randomized clinical
      trial.
AB  - PURPOSE: Transanal endoscopic microsurgery (TEM) is a three-dimensional viewing
      endoscopic system procedure which provides access to rectal tumors through a
      rectoscope. Two-dimensional transanal endoscopic operation (TEO), with the
      introduction of high-definition vision, achieves results that are comparable to
      those of the classical TEM. The main aim of the study was to compare the
      effectiveness of TEO and TEM systems in a prospective, randomized clinical trial.
      METHOD:  STUDY POPULATION: patients meeting inclusion criteria for diagnosis of
      rectal tumors with curative intent. Sample size, 36 patients. Patients were
      randomized to receive one of the two procedures. Study variables recorded were
      the following: preoperative data (time taken to assemble equipment, surgical
      time, quality of pneumorectum), postoperative morbidity and mortality, pathology
      study of the tumors, and economic analysis. RESULTS: Thirty-six patients were
      analyzed according to intention to treat. Two patients were excluded. The final
      per-protocol analysis was 34 patients. There were no significant differences in
      the preoperative or operative variables, quality of pneumorectum, postoperative
      variables, or pathology results. A trend toward benefit was observed in favor of
      TEO in time required for assembly, surgical suture time, and total surgical time
      though the differences were not statistically significant. Statistically
      significant differences were found in terms of the total cost of the procedure,
      with mean costs of 2,031 <euro> +/- 440 for TEO and 2,603 <euro> +/- 507 for TEM
      (95% CI 218.15-926.486 <euro>, p = 0.003). CONCLUSION: No technical or clinical
      differences were observed between the results obtained with the two systems
      except lower cost with TEO.

PMID- 24676507
TI  - The development of consensus for complete mesocolic excision (CME) should
      commence with standardisation of anatomy and related terminology.

PMID- 24676518
TI  - A biomechanical review of the techniques used to estimate or measure resistive
      forces in swimming.
AB  - Resistive or drag forces encountered during free swimming greatly influence the
      swim performance of elite competitive swimmers. The benefits in understanding the
      factors which affect the drag encountered will enhance performance within the
      sport. However, the current techniques used to experimentally measure or estimate
      drag values are questioned for their consistency, therefore limiting
      investigations in these factors. This paper aims to further understand how the
      resistive forces in swimming are measured and calculated. All techniques outlined
      demonstrate both strengths and weaknesses in the overall assessment of free
      swimming. By reviewing all techniques in this area, the reader should be able to
      select which one is best depending on what researchers want to gain from the
      testing. 

PMID- 24676519
TI  - Evaluating the acromion marker cluster as a method for measuring scapular
      orientation in children with brachial plexus birth palsy.
AB  - Several studies have described using an acromion marker cluster for measuring
      scapular orientation in healthy adults performing planar motions. It is unknown
      whether the acromion marker cluster method will provide the same level of
      accuracy in children with brachial plexus birth palsy. This study compared this
      method to palpation for calculating scapular orientation in children with
      brachial plexus birth palsy performing clinically relevant movements. Scapular
      orientation in ten patients was determined by palpation and an acromion marker
      cluster in neutral and six Modified Mallet positions. RMSEs and mean relative
      errors were calculated. Resultant RMSEs ranged from 5.2 degrees to 21.4 degrees.
      The averages of the mean relative errors across all positions for each axis were
      177.4% for upward/downward rotation, 865.0% for internal/external rotation, and
      166.2% for anterior/posterior tilt. The acromion marker cluster method did not
      accurately measure scapular rotation relative to the total movement on an
      individual or group basis in the population. With most relative errors over 100%,
      the acromion marker cluster method often produced errors larger than the actual
      measured motion. The accuracy of the acromion marker cluster method limits its
      use as a clinical tool for measuring scapular kinematics on children with
      brachial plexus birth palsy. 

PMID- 24676520
TI  - Association between contraction-induced increases in elbow flexor muscle
      thickness and distal biceps brachii tendon moment arm depends on the muscle
      thickness measurement site.
AB  - The purpose of this study was to investigate how the contraction-induced increase
      in distal biceps brachii tendon moment arm is related to that in elbow flexor
      muscle thickness, with a specific emphasis on the influence of the site-related
      differences in muscle thickness. The moment arm and muscle thickness were
      determined from sagittal and cross-sectional images, respectively, of the right
      arm obtained by magnetic resonance imaging of nine young men. The muscle
      thickness was measured at levels from the reference site (60% of the upper arm
      length from the acromial process of the scapula to the lateral epicondyle of the
      humerus) to 60 mm distal to it (every 10 mm; 7 measurement sites). At 80 degrees 
      of elbow flexion, the moment arm and muscle thickness were determined at rest and
      during 60% of maximal voluntary contraction (60%MVC) of isometric elbow flexion.
      Only the relative change from rest to 60%MVC in muscle thickness at the level 60
      mm distal to the reference site correlated significantly with that of the moment
      arm. This result indicates that the contraction-induced increase in distal biceps
      brachii tendon moment arm is related to that in elbow flexor muscle thickness
      near the corresponding muscle-tendon junction. 

PMID- 24676521
TI  - Human carrying simulation with symmetric and asymmetric loads using optimization.
AB  - Human carrying is simulated in this work by using a skeletal digital human model
      with 55 degrees of freedom. An optimization-based approach is used to predict the
      carrying motion with symmetric and asymmetric loads. In this process, the model
      predicts joint dynamics using optimization schemes and task-based physical
      constraints. The results indicate that the model can predict different carrying
      strategies during symmetric and asymmetric load-carrying tasks. The model can
      also indicate the risk factors for extreme loading situations. With such robust
      prediction capability, the model could be used for biomedical and ergonomic
      studies. 

PMID- 24676508
TI  - Cardiovascular actions of GLP-1 and incretin-based pharmacotherapy.
AB  - Incretin-based therapy became recently available as antihyperglycemic treatment
      for patients with type 2 diabetes (T2DM). Incretin therapy comprises glucagon
      like peptide receptor agonists (GLP-1RA) and dipeptidyl-peptidase 4 inhibitors
      (DPP4-I): these classes of drugs not only have the ability to reduce blood
      glucose, but also can exert several cardioprotective effects. They have been
      shown to positively influence some risk factors for cardiovascular disease (CVD),
      to improve endothelial function, and to directly affect cardiac function. For
      these reasons incretins are considered not only antidiabetic drugs, but also
      cardiovascular effective. The first clinical trials aimed to demonstrate the
      safety of DPP4 inhibitors have been recently published: their clinical
      significance will be discussed in light of the prior experimental findings. 

PMID- 24676522
TI  - A comparison of computation methods for leg stiffness during hopping.
AB  - Despite the presence of several different calculations of leg stiffness during
      hopping, little is known about how the methodologies produce differences in the
      leg stiffness. The purpose of this study was to directly compare Kleg during
      hopping as calculated from three previously published computation methods. Ten
      male subjects hopped in place on two legs, at four frequencies (2.2, 2.6, 3.0,
      and 3.4 Hz). In this article, leg stiffness was calculated from the natural
      frequency of oscillation (method A), the ratio of maximal ground reaction force
      (GRF) to peak center of mass displacement at the middle of the stance phase
      (method B), and an approximation based on sine-wave GRF modeling (method C). We
      found that leg stiffness in all methods increased with an increase in hopping
      frequency, but Kleg values using methods A and B were significantly higher than
      when using method C at all hopping frequencies. Therefore, care should be taken
      when comparing leg stiffness obtained by method C with those calculated by other
      methods. 

PMID- 24676524
TI  - The influence of different force and pressure measuring transducers on lower
      extremity kinematics measured during running.
AB  - In running analyses where both kinetic and kinematic information is recorded,
      participants are required to make foot contact with a force and/or pressure
      measuring transducer. Problems arise if participants modify their gait patterns
      to ensure contact with the device. There is currently a paucity of research
      investigating the influence of different underfoot kinetic measuring devices on 3
      dimensional kinematics of running. Fifteen participants ran at 4.0 m/s in four
      different conditions: over a floor embedded force plate, Footscan, Matscan, and
      with no device. Three-dimensional angular kinematic parameters were collected
      using an eight camera motion analysis system. Hip, knee, and ankle joint
      kinematics were contrasted using repeated-measures ANOVAs. Participants also
      rated their subjective comfort in striking each of the three force measuring
      devices. Significant differences from the uninhibited condition were observed
      using the Footscan and Matscan in all three planes of rotation, whereas
      participants subjectively rated the force plate significantly more comfortable
      than either the Footscan/Matscan devices. The findings of the current
      investigation therefore suggest that the disguised floor embedded force plate
      offers the most natural running condition. It is recommended that analyses using
      devices such as the Footscan/Matscan mats overlying the laboratory surface during
      running should be interpreted with caution. 

PMID- 24676525
TI  - Comparison of stance phase knee joint angles and moments using two different
      surface marker representations of the proximal shank in walkers and runners.
AB  - Efforts to compare different surface marker configurations in 3-dimensional
      motion analysis are warranted as more complex and custom marker sets become more
      common. At the knee, different markers can been used to represent the proximal
      shank. Often, two anatomical markers are placed over the femoral condyles, with
      their midpoint defining both the distal thigh and proximal shank segment ends.
      However, two additional markers placed over the tibial plateaus have been used to
      define the proximal shank end. For this experiment, simultaneous data for both
      proximal shank configurations were independently collected at two separate
      laboratories by different investigators, with one laboratory capturing a walking
      population and the other a running population. Common discrete knee joint
      variables were then compared between marker sets in each population. Using the
      augmented marker set, peak knee flexion after weight acceptance was less (1.2-1.7
      degrees , P < .02) and peak knee adduction was greater (0.7-1.4 degrees , P <
      .001) in both data sets. Similarly, the calculated peak knee flexion moment was
      less by 15-20% and internal rotation moment was greater by 11-18% (P < .001).
      These results suggest that the calculation of knee joint mechanics are influenced
      by the proximal shank's segment endpoint definition, independent of dynamic task,
      investigator, laboratory environment, and population in this study. 

PMID- 24676526
TI  - Leg dominance may not be a predictor of asymmetry in peak joint moments and
      ground reaction forces during sit-to-stand movements.
AB  - Sit-to-stand transfer is a common prerequisite for many daily tasks. Literature
      often assumes symmetric behavior across the left and right side. Although this
      assumption of bilateral symmetry is prominent, few studies have validated this
      supposition. This pilot study uniquely quantifies peak joint moments and ground
      reaction forces (GRFs), using a Euclidian norm approach, to evaluate bilateral
      symmetry and its relation to lower limb motor-dominance during sit to stand in
      ten healthy males. Peak joint moments and GRFs were determined using a motion
      capture system and inverse dynamics. This analysis included joint moment
      contributions from all three body planes (sagittal, coronal, and axial) as well
      as vertical and shearing GRFs. A paired, one-tailed t test was used, suggesting
      asymmetrical joint moment development in all three lower extremity joints as well
      as GRFs (P < .05). Furthermore, using an unpaired two-tailed t test, asymmetry
      developed during these movements does not appear to be predictable by
      participants' lower limb motor-dominance (P < .025). Consequently, when
      evaluating sit-to-stand it is suggested the effects of asymmetry be considered in
      the interpretation of data. The absence of a relationship between dominance and
      asymmetry prevents the suggestion that one side can be tested to infer behavior
      of the contralateral. 

PMID- 24676527
TI  - Upregulation of the splice variant MUC4/Y in the pancreatic cancer cell line MIA
      PaCa-2 potentiates proliferation and suppresses apoptosis: new insight into the
      presence of the transcript variant of MUC4.
AB  - MUC4/Y, the transcript variant 4 of MUC4, lacks exon 2 as compared with the
      transcript variant 1 of MUC4. To date, direct evidence for the function of MU4/Y
      remains to be reported. Previous studies based their hypotheses regarding the
      function of MUC4/Y on the characteristic structure domains of this variant. The
      aim of the present study was to investigate the specific function of MUC4/Y. The
      pancreatic cancer cell line MIA PaCa-2 with low MUC4/Y expression was used to
      establish a stable cell model of MUC4/Y upregulation using a lentivirus vector
      system. Results showed that MUC4/Y anchored on the cytomembrane and affected cell
      morphology and cell cycle. Functional analyses indicated that MUC4/Y upregulation
      slightly potentiated cell proliferation and significantly suppressed apoptosis
      both in vivo and in vitro. Further studies revealed that the JNK and AKT
      signalling pathways were activated. Meanwhile, MUC4/Y upregulation elicited
      minimal effect on the phosphorylation level of HER2, a membrane partner of MUC4.
      These results suggest that MUC4/Y promotes tumour progression through its anti
      apoptotic and weak mitogenic effect on MIA PaCa-2 cells.

PMID- 24676528
TI  - Modular syntheses of H4octapa and H2dedpa, and yttrium coordination chemistry
      relevant to 86Y/90Y radiopharmaceuticals.
AB  - The ligands H2dedpa, H4octapa, p-SCN-Bn-H2dedpa, and p-SCN-Bn-H4octapa were
      synthesized using a new protection chemistry approach, with labile tert-butyl
      esters replacing the previously used methyl esters as protecting groups for
      picolinic acid moieties. Additionally, the ligands H2dedpa and p-SCN-Bn-H2dedpa
      were synthesized using nosyl protection chemistry for the first time. The use of
      tert-butyl esters allows for deprotection at room temperature in trifluoroacetic
      acid (TFA), which compares favorably to the harsh conditions of refluxing HCl (6
      M) or LiOH that were previously required for methyl ester cleavage. H4octapa has
      recently been shown to be a very promising (111)In and (177)Lu ligand for
      radiopharmaceutical applications; therefore, coordination chemistry studies with
      Y(3+) are described to assess its potential for use with (86)Y/(90)Y. The
      solution chemistry of H4octapa with Y(3+) is shown to be suitable via solution
      NMR studies of the [Y(octapa)](-) complex and density functional theory (DFT)
      calculations of the predicted structure, suggesting properties similar to those
      of the analogous In(3+) and Lu(3+) complexes. The molecular electrostatic
      potential (MEP) was mapped onto the molecular surface of the DFT-calculated
      coordination structures, suggesting very similar and even charge distributions
      between both the Lu(3+) and Y(3+) complexes of octapa(4-), and coordinate
      structures between 8 (ligand only) and 9 (ligand and one H2O). Potentiometric
      titrations determined H4octapa to have a formation constant (log K(ML)) with
      Y(3+) of 18.3 +/- 0.1, revealing high thermodynamic stability. This preliminary
      work suggests that H4octapa may be a competent ligand for future (86)Y/(90)Y
      radiopharmaceutical applications.

PMID- 24676529
TI  - Acral acquired cutis laxa associated with IgA multiple myeloma, joint hyperlaxity
      and urticarial neutrophilic dermatosis.

PMID- 24676530
TI  - Recovery of electric energy from formate by using a recombinant strain of
      Escherichia coli.
AB  - Recombinant Escherichia coli cells were applied for the recovery of electric
      energy from formate. Initially, the fdh gene, which encodes formate dehydrogenase
      (FDH) of Mycobacterium vaccae, was introduced into E. coli cells to allow
      efficient degradation of formate. The constructed microbial fuel cell (MFC) with
      E. coli BW25113 cells carrying fdh gene showed appreciable generation of current
      density in the presence of formate as a substrate. Current density and
      polarization curves revealed that the performance of MFC under examined
      conditions was limited by the electron transfer from bulk liquid to the electrode
      surface; accordingly, agitation resulted in an increase in the current density
      and achieved a coulombic efficiency of 21.7 % on the basis of formate consumed.
      Thus, gene recombination enables E. coli cells to utilize formate as a fuel for
      MFC. 

PMID- 24676531
TI  - Integrated analysis of expression profiling data identifies three genes in
      correlation with poor prognosis of triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) shows more aggressive clinical behavior and
      poorer outcome than non-triple-negative breast cancer (NTNBC), and cannot be
      treated either via endocrine therapy or by Trastuzumab. For TNBC, chemotherapy is
      currently the mainstay of systemic medical treatment, the lack of more efficient
      options of treatment has been a problem in breast cancer prevention. In this
      study, we aimed to find genes related to prognosis in TNBC by bioinformatic
      analysis and to provide therapeutic candidates for TNBC treatment. We compared
      the differences in gene expression levels between cancer patients and healthy
      individuals across five breast cancer microarray databases to generate a gene
      cohort specifically upregulated in the NTNBC subtype, whose expression levels are
      >=2-fold higher in TNBC compared to NTNBC and healthy individuals. Another two
      databases with clinical information were applied for following Kaplan-Meier
      analysis, and high expression of BIRC5, CENPA and FAM64A in this cohort were
      found to be related to poor survival (OS, DMFS, DFS and RFS). This correlation
      was also seen in patients at early stages and grades. On the other hand, the
      outcome of patients with synchronous upregulation of these three genes was the
      worst, while those with synchronous low gene level was the best. In conclusion,
      BIRC5, CENPA and FAM64A are specifically upregulated in TNBC, and the high
      expression of these three genes is associated with poor breast cancer prognosis,
      suggesting their clinical implication as therapeutic targets in TNBC. 

PMID- 24676532
TI  - The diagnostic yield of upper endoscopy procedures in children- is it cost
      effective?
AB  - Upper endoscopy is an invaluable tool for the diagnosis and treatment of various
      gastrointestinal symptoms in children. Over the years, the number of endoscopic
      procedures performed in different medical centers has increased considerably and
      the cost associated with the procedure has become unsustainable. Recently, the US
      government has investigated this topic and has suggested steps to reduce the cost
      and use of endoscopic procedures in the adult population, changes that have not
      been accepted favorably by the American Gastroenterology Associations (AGA). In
      the present report, we evaluate the diagnostic yield of the procedure in children
      and suggest steps to reduce the annual number of upper endoscopic procedures in
      children. The diagnostic yield and the cost-effectiveness of the procedure are
      also discussed. 

PMID- 24676535
TI  - Therapeutic efficacy of vacuum-assisted-closure therapy in the treatment of
      lymphatic complications following peripheral vascular interventions and
      surgeries.
AB  - OBJECTIVES: Lymphatic complications, lymphocele and lymphorrhea being the
      leading, are generally encountered after vascular interventions and surgeries.
      The present study aimed to evaluate the outcomes of vacuum-assisted-closure (VAC)
      therapy, which we frequently prefer as the first-choice treatment for such
      complications. MATERIALS AND METHODS: Among patients undergoing peripheral
      vascular intervention or surgery between January 2008 and February 2012, the
      medical files of 21 patients who received VAC therapy or other treatment due to
      symptomatic lymphatic complications were retrospectively analyzed and the results
      were discussed. RESULTS: Group I consisted of 10 patients (three with lymphocele
      and seven with lymphorrhea) who underwent VAC therapy as the first-choice
      treatment, Group II consisted of 11 patients of which 7 patients received various
      therapies before VAC therapy and 4 patients received other treatments alone. The
      patients who received VAC therapy as the primary therapy demonstrated more rapid
      wound healing, early drainage control, and shorter hospital stay. The mean
      hospital medical cost was ?1038 (range, ?739-1826) for the patients who primarily
      underwent VAC therapy; it was calculated to be ?2137 (range, ?1610-3130) for the
      other patients (p=0.001). CONCLUSION: In addition to its safety and good clinical
      outcomes, VAC therapy also has economic advantages and should be the primary
      method for the treatment of lymphatic complications.

PMID- 24676536
TI  - Giant midline abdominal incisional herniae repair through combined retro-rectus
      mesh placement and components separation: experience from a single centre.
AB  - AIMS: Giant midline abdominal wall incisional herniae require
      repair/reconstruction to restore the structural and functional continuity of the
      anterior abdominal wall. We describe here our approach to these demanding cases
      through a combined retro-rectus mesh placement and components separation and
      their overall functional outcome. METHODS: A retrospective analysis of a
      prospectively collected data was carried out and 28 patients who underwent giant
      (>=15 cm) midline incisional hernia reconstruction were identified in a large
      district general hospital between 2007 and 2013 with a median follow-up of 34 (6
      76) months. RESULTS: Demographic data of our series include age of 60 (median)
      (30-87) years with a M:F ratio of 12:16, length of symptomatic hernia 18 (median)
      (12-36) months, more than two previous laparotomies (15), bowel obstructive
      symptoms (7) and recurrent herniation (7). BMI recorded was 32 (median) (24-46)
      and ASA of II (median) (I-III). Co-morbidities included cardiac disease (6),
      diabetes (6), respiratory disease (4) and systemic immunocompromise (2).
      Operative and technical details showed operative duration to be 180 (median) min,
      cranio-caudal rectus sheath defect 21 (median) cm, transverse rectus sheath
      defect 15 (median) cm, cross-sectional area of fascial defect 300 (median) cm(2)
      and size of mesh 690 (median) cm(2). Seven (25 %) developed short-term post
      operative complications: grade I seromata all resolving spontaneously (5); grade
      II superficial wound infections (2). Twenty-five (89 %) were completely
      asymptomatic at 34 (median) months' follow-up; 2 (7 %) reported mild pain, but
      not limiting any activity; 1 (4 %) described pain occasionally limiting activity.
      There was no clinical recurrence with one patient developing global bulging.
      CONCLUSIONS: Our series is comparable to the literature in patient cohort
      demographics, co-morbidity and risk factor profile; however, we demonstrate an
      excellent intermediate term outcome with no clinical recurrence and an
      improvement in quality of life, through their ability to perform normal day to
      day activities.

PMID- 24676537
TI  - Antibacterial performance of nanocrystallined titania confined in mesoporous
      silica nanotubes.
AB  - In this paper, we study synthesis and characteristics of mesoporous silica
      nanotubes modified by titanium dioxide, as well as their antimicrobial properties
      and influence on mitochondrial activity of mouse fibroblast L929. Nanocrystalized
      titania is confined in mesopores of silica nanotubes and its light activated
      antibacterial response is revealed. The analysis of the antibacterial effect on
      Escherichia coli. (ATCC 25922) shows strong enhancement during irradiation with
      the artificial visible and ultraviolet light in respect to the commercial
      catalyst and control sample free from the nanomaterials. In darkness, the
      mesoporous silica/titania nanostructures exhibited antibacterial activity
      dependent on the stirring speed of the suspension containing nanomaterials.
      Obtained micrograph proved internalization of the sample into the microorganism
      trough the cell membrane. The analysis of the mitochondrial activity and amount
      of lactate dehydrogenase released from mouse fibroblast cells L929 in the
      presence of the sample were determined with LDH and WST1 assays, respectively.
      The synthesized silica/titania antibacterial agent also exhibits pronounced
      photoinduced inactivation of the bacterial growth under the artificial visible
      and UV light irritation in respect to the commercial catalyst. Additionally,
      mesoporous silica/titania nanotubes were characterized in details by means of
      high resolution transmission electron microscopy (HR-TEM), XRD and BET Isotherm. 

PMID- 24676538
TI  - Downregulation of LKB1 suppresses Stat3 activity to promote the proliferation of
      esophageal carcinoma cells.
AB  - The tumor suppressor liver kinase B1 (LKB1) encodes a serine/threonine kinase.
      The defect in LKB1 is the primary cause of Peutz-Jeghers syndrome (PJS).
      Inactivation of LKB1 by mutations or loss of LKB1 expression is associated with
      ovarian, lung and pancreatic cancer; however, the correlation between LKB1 and
      esophageal carcinoma remains unknown. Thus, quantitative PCR was performed to
      determine the clinical significance of LKB1 expression in 60 cases of esophageal
      cancer and its adjacent normal epithelium. LKB1 expression was observed to
      significantly downregulate the accompanying cancer progression, which was
      verified at the protein level by western blot analysis. Furthermore, the
      phosphorylated signal transducer and activator of transcription 3 (Stat3) level
      is reversibly associated with LKB1 expression. To determine the function of LKB1
      in esophageal cancer, LKB1 expression is induced in TE1 esophageal cancer cells.
      The results show that LKB1 overexpression suppresses the proliferation of TE1
      cells, downregulates the expression of cyclin D1 and Myc and represses Stat3
      phosphorylation. Suppression of cell proliferation and cyclin D1 expression by
      LKB1 is fully inhibited by constitutively active Stat3C coexpression, suggesting
      that LKB1 inhibits esophageal cancer cell proliferation through suppression of
      Stat3 transaction. In conclusion, downregulation of LKB1 expression suppresses
      Stat3 activity that may promote tumor growth during esophageal cancer
      progression.

PMID- 24676539
TI  - [Mild dementia and driving ability. Part 2: Assessment and its consequences in
      practice].
AB  - The legal framework and the essentials in traffic and transport psychology and
      statistics were described in part 1. Safe driving depends on different sensory
      and mental processes interacting in a complicated manner. Physiological changes
      and--even more importantly--a variety of diseases result in impaired performance
      in these functional areas. Moderate to severe dementia certainly means that the
      person is no longer fit to drive, whereas driving ability may be maintained in
      mild dementia for some time. There are different approaches and assessment tools,
      but a single test that could, on its own, answer the question whether a patient
      with mild dementia is fit to drive does not exist. Driving ability is not only
      determined by cognitive function. Further assessment of possible risk factors and
      overall functioning is necessary. If dementia is diagnosed, then the question of
      fitness to drive must be promptly discussed with the patient because during the
      course of dementia driving ability will inevitably be lost. The conclusion of the
      assessment of driving ability must not be pronounced like a verdict, the
      physician should rather counsel and support the patient and his family on the
      difficult road towards driving cessation.

PMID- 24676540
TI  - Evidence of short-range electron transfer of a redox enzyme on graphene oxide
      electrodes.
AB  - Direct electron transfer (DET) between redox enzymes and electrode surfaces is of
      growing interest and an important strategy in the development of biofuel cells
      and biosensors. Among the nanomaterials utilized at electrode/enzyme interfaces
      to enhance the electronic communication, graphene oxide (GO) has been identified
      as a highly promising candidate. It is postulated that GO layers decrease the
      distance between the flavin cofactor (FAD/FADH2) of the glucose oxidase enzyme
      (GOx) and the electrode surface, though experimental evidence concerning the
      distance dependence of the rate constant for heterogeneous electron-transfer
      (k(het)) has not yet been observed. In this work, we report the experimentally
      observed DET of the GOx enzyme adsorbed on flexible carbon fiber (FCF) electrodes
      modified with GO (FCF-GO), where the k(het) between GO and electroactive GOx has
      been measured at a structurally well-defined interface. The curves obtained from
      the Marcus theory were used to obtain k(het), by using the model proposed by
      Chidsey. In agreement with experimental data, this model proved to be useful to
      systematically probe the dependence of electron transfer rates on distance, in
      order to provide an empirical basis to understand the origin of interfacial DET
      between GO and GOx. We also demonstrate that the presence of GO at the
      enzyme/electrode interface diminishes the activation energy by decreasing the
      distance between the electrode surface and FAD/FADH2.

PMID- 24676541
TI  - Cardiopulmonary exercise testing demonstrates maintenance of exercise capacity in
      patients with hypoxemia and pulmonary arteriovenous malformations.
AB  - BACKGROUND: Patients with pulmonary arteriovenous malformations (PAVMs) are
      unusual because hypoxemia results from right-to-left shunting and not airway or
      alveolar disease. Their surprisingly well-preserved exercise capacity is not
      generally appreciated. METHODS: To examine why exercise tolerance is preserved,
      cardiopulmonary exercise tests were performed while breathing room air in 21
      patients with radiologically proven PAVMs, including five restudied 3 to 12
      months after embolization when their PAVMs had regressed. Where physiologic
      matching was demonstrable, comparisons were made with 12 healthy control
      subjects. RESULTS: The majority of patients achieved their predicted work rate
      despite a resting arterial oxygen saturation (SaO2) of 80% to 96%. Peak work rate
      and oxygen consumption (VO2) were no lower in patients with more hypoxemia.
      Despite higher SaO2 following embolization (median, 96% and 90%; P = .009),
      patients achieved similar work rates and similar peak VO2. Strikingly, treated
      patients reset to virtually identical peak oxygen pulses (ie, VO2 per heart beat)
      and in many cases to the same point on the peak oxygen pulse/work rate plot. The
      21 patients had increased minute ventilation (VE) for given increases in CO2
      production (VE/VCO2 slope), but perceived dyspnea was no greater than in the 12
      control subjects or in the same patients before compared to after embolization
      comparison. Overall, work rate and peak VO2 were associated not with oxygenation
      parameters but with VE/VCO2 slope, BMI, and anaerobic threshold. CONCLUSIONS:
      Patients with hypoxemia and PAVMs can maintain normal oxygen delivery/VO2 during
      peak exercise. Following improvement of SaO2 by embolization, patients appeared
      to reset compensatory mechanisms and, as a result, achieved similar peak VO2 per
      heart beat and peak work rates.

PMID- 24676542
TI  - Heme oxygenase-1 silencing increases the sensitivity of human osteosarcoma MG63
      cells to arsenic trioxide.
AB  - Arsenic trioxide (ATO) has been successfully used to treat leukemia and some
      solid malignant tumors. Our previous study regarding the effects of ATO on
      mesenchymal-derived human osteosarcoma MG63 cells showed that heme oxygenase-1
      (HO-1) was strongly induced upon treatment with ATO. The present study sought to
      investigate the effect of silencing HO-1 on the sensitivity of osteosarcoma cells
      to ATO to determine the potential for therapeutic applications. Small hairpin RNA
      (shRNA)-mediated interference was used to silence HO-1 in MG63 cells. Viability,
      apoptosis, and intracellular reactive oxygen species (ROS) of the cells were
      assessed to evaluate the sensitivity of the cells to ATO as well as the potential
      mechanisms responsible. shRNA-mediated interference prevented the induction of HO
      1, increased cell death, and increased intracellular ROS levels in MG63 cells
      upon treatment with ATO. Silencing HO-1 increased the susceptibility of MG63
      cells to the chemotherapeutic drug ATO by enhancing intracellular accumulation of
      ROS. Our results suggest that the inhibition of HO-1 could improve the outcome of
      osteosarcoma treated with ATO. 

PMID- 24676543
TI  - Molecular insights into the association of obesity with breast cancer risk:
      relevance to xenobiotic metabolism and CpG island methylation of tumor suppressor
      genes.
AB  - Obesity, genetic polymorphisms of xenobiotic metabolic pathway, hypermethylation
      of tumor suppressor genes, and hypomethylation of proapoptotic genes are known to
      be independent risk factors for breast cancer. The objective of this study is to
      evaluate the combined effect of these environmental, genetic, and epigenetic risk
      factors on the susceptibility to breast cancer. PCR-RFLP and multiplex PCR were
      used for the genetic analysis of six variants of xenobiotic metabolic pathway.
      Methylation-specific PCR was used for the epigenetic analysis of four genetic
      loci. Multifactor dimensionality reduction analysis revealed a significant
      interaction between the body mass index (BMI) and catechol-O-methyl transferase
      H108L variant alone or in combination with cytochrome P450 (CYP) 1A1m1 variant.
      Women with "Luminal A" breast cancer phenotype had higher BMI compared to other
      phenotypes and healthy controls. There was no association between the BMI and
      tumor grade. The post-menopausal obese women exhibited lower glutathione levels.
      BMI showed a positive association with the methylation of extracellular
      superoxide dismutase (r = 0.21, p < 0.05), Ras-association (RalGDS/AF-6) domain
      family member 1 (RASSF1A) (r = 0.31, p < 0.001), and breast cancer type 1
      susceptibility protein (r = 0.19, p < 0.05); and inverse association with
      methylation of BNIP3 (r = -0.48, p < 0.0001). To conclude based on these results,
      obesity increases the breast cancer susceptibility by two possible mechanisms:
      (i) by interacting with xenobiotic genetic polymorphisms in inducing increased
      oxidative DNA damage and (ii) by altering the methylome of several tumor
      suppressor genes. 

PMID- 24676544
TI  - Lysophosphatidic acid receptor-5 negatively regulates cell motile and invasive
      activities of human sarcoma cell lines.
AB  - LPA signaling via LPA receptors [LPA receptor-1 (LPA1)-LPA6] mediates the several
      cellular responses in cancer cells, including cell motility and invasion. In the
      present study, to investigate a role of LPA5 in the cell motile and invasive
      activities of sarcoma cells, LPAR5 knockdown (HOSL5 and HT1080L5) cells were
      generated from human osteosarcoma HOS and fibrosarcoma HT1080 cells,
      respectively. In cell motility assays with cell culture inserts, HOSL5 and
      HT1080L5 cells indicated the high cell motile activities, compared with control
      cells. The cell invasive activities of HOSL5 and HT1080L5 cells were
      significantly higher than those of control cells. Moreover, the activities of
      matrix metalloproteinase (MMP)-2 and MMP-9 were measured by gelatin zymography.
      MMP-2 was significantly activated in HOSL5 cells, but not MMP-9. The elevated
      activities of MMP-2 and MMP-9 were found in HT1080L5 cells, in comparison with
      control cells. These results suggest that LPA signaling via LPA5 negatively
      regulates the cell motile and invasive activities of human sarcoma cells. 

PMID- 24676545
TI  - Increased DNase I activity in diabetes might be associated with injury of
      pancreas.
AB  - DNase I is an endonuclease responsible to destruction of chromatin during
      apoptosis. However, its role in diabetes is still unclear. With blood samples
      from our previous study related to type 2 diabetes, we examined the DNase I
      activity in the serum of these patients and the role of DNase I in the injury of
      pancreas was further investigated in rats and INS-1 cells. Serum and pancreatic
      tissues from human and rats were used for the study. Insulin resistance and
      diabetes were induced by high fat diet and STZ injection, respectively. DNase I
      activity was determined by radial enzyme-diffusion method. Expressions of DNase I
      and caspase-3 in pancreas were determined in rat pancreatic tissues and INS-1
      cells. Apoptosis of INS-1 cells was determined by both TUNEL assay and Flow
      Cytometry. There was a significant elevation of DNase I activity in serum of
      patients with type 2 diabetes and rats with STZ injection. Moreover, increase in
      DNase I expression was observed in the pancreas of diabetic person and rats.
      Furthermore, high glucose induced both DNase I and caspase-3 expression and at
      the same time increased apoptosis rate of INS-1 cells. In conclusion, elevated
      DNase I in diabetes may be related to pancreatic injury and could be one of the
      causes that induce diabetes. 

PMID- 24676546
TI  - Is treatment under general anaesthesia associated with dental neglect and dental
      disability among caries active preschool children?
AB  - AIM: To study if treatment under general anaesthesia (GA) is associated with
      dental neglect or dental disability. STUDY DESIGN: This was a retrospective
      study. METHODS: Dental records of all children in the age 0-6 years who underwent
      GA at a specialist paediatric dentistry clinic during 2006-2011 were studied with
      regard to decayed-missed-filled teeth, traumatic injuries, emergency visits,
      behaviour management problems and the history of attendance. The final sample
      consisted of 134 children. Matched controls were selected among recall patients
      who had not received treatment under GA. STATISTICS: Fishers exact test or
      Pearson Chi-square test analysed response distribution and comparisons between
      groups, and for multivariate analyses, logistic regression was used. RESULTS: The
      results show that children treated under GA had significantly higher caries
      prevalence, apical periodontitis and infections due to pulpal necrosis. Dental
      neglect as well as dental disability was significantly more prevalent in the GA
      group compared to the control group. In a multivariate analysis with dental
      neglect as independent factor, dental disability was the only significant factor
      (p = 0.006). CONCLUSIONS: Children treated under general anaesthesia were
      significantly more often diagnosed with both dental neglect and dental
      disability. Dental disability was the only factor significantly related to dental
      neglect. There is a need for improved documentation in the dental records to
      better identify dental neglect and dental disability, and also a continued
      training of dentists regarding child protection.

PMID- 24676547
TI  - Parental acceptance of behaviour-management techniques used in paediatric
      dentistry and its relation to parental dental anxiety and experience.
AB  - AIM: The aim of this study was to examine the acceptance by Greek parents of nine
      behaviour-management techniques and its association with several possible
      confounding factors. STUDY DESIGN: Following ethical approval, 106 parents whose
      3- to 12-year-old children had been receiving treatment in a university
      postgraduate paediatric dental clinic, and 123 parents of children from a private
      paediatric dental practice agreed to participate. METHODS: After being shown a
      video with nine behaviour-management techniques, parents rated the acceptance of
      each technique on a 0-10 scale. They were then asked to complete a questionnaire
      about demographics, their previous dental experience and dental anxiety (modified
      Corah dental anxiety scale). RESULTS: The best accepted technique was tell-show
      do (9.76 +/- 0.69), followed by parental presence/absence (PPA) technique (7.83
      +/- 3.06) and nitrous oxide inhalation sedation (7.09 +/- 3.02). The least
      accepted techniques were passive restraint (4.21 +/- 3.84) and general
      anaesthesia (4.21 +/- 4.02). No correlations were found between acceptance of any
      individual management technique and parental age, gender, income, education,
      dental experience and dental anxiety or the child's age, gender and dental
      experience. Parents whose children had been treated at the University clinic had
      lower income and educational levels, and rated passive restraint, oral sedation
      and general anaesthesia higher than those from the private practice. When the
      parents were specifically asked to choose between general anaesthesia over any of
      the active or passive restraint, hand-over-mouth and voice control techniques,
      10% preferred general anaesthesia, and these parents reported statistically
      significant more negative dental experience but not higher dental anxiety.
      STATISTICS: Statistical significance of differences was explored using the Tukey
      Kramer method. CONCLUSION: There was no correlation between parental dental
      experience and dental anxiety and the acceptance of any specific behaviour
      management technique. However, parents with negative dental experience would
      prefer general anaesthesia over any of active or passive restraint, hand-over
      mouth and voice control techniques. PPA is a highly acceptable technique for
      Greek parents.

PMID- 24676548
TI  - Analysis of dental care of children receiving comprehensive care under general
      anaesthesia at a teaching hospital in England.
AB  - OBJECTIVES: This study aimed to analyse the characteristics of comprehensive
      dental care provided under general anaesthesia (CDGA) and to review the
      additional treatment required by children over the 6 years subsequent to CDGA.
      METHOD: Information collected from hospital records for the 6-year period
      following the first CDGA included the types of dental treatment performed at
      CDGA, the return rates for follow-up appointments, further treatment required
      subsequent to CDGA and the types of dental treatment performed at repeat DGA.
      RESULTS: The study population consisted of 263 children, of whom 129 had a
      significant medical history, with mean age of 6.7 years. The results revealed
      that the waiting time for CDGA was significantly shorter in children who had a
      significant medical history, with 49% being admitted for CDGA within 3 months of
      pre-GA assessment, as compared to 29% of healthy children. 67% of children had
      follow-up care recorded, with a slightly higher proportion of children with
      significant medical history returning for follow-up [70% (90/129)] compared with
      65% (87/134) of healthy children. Re-treatment rates were 34% (88/263), the
      majority of cases being treated under local analgesia (42/88). 34 of 263 children
      had repeat DGA (12.9%). Of these 71% (24/34) were children with significant
      medical history. The mean age at repeat DGA was 9 years. In 25 of 34 children
      (74%), repeat DGA was due to trauma, oral pathology, supernumerary removal,
      hypomineralized teeth or new caries of previously sound or un-erupted teeth at
      CDGA. The ratio of extraction over restoration (excluding fissure sealants)
      performed at repeat DGA was 2.8, compared with the ratio of 1.3 in the initial
      CDGA. CONCLUSIONS: There was a higher ratio of extraction over restorations at
      the repeat DGA. This suggests that the prescribed treatments at repeat DGA were
      more aggressive as compared to the initial CDGA in 1997. The majority of the
      treatment required at repeat DGA was to treat new disease.

PMID- 24676549
TI  - Management of a prediabetes case with the DPP-4 inhibitor sitagliptin.
AB  - OBJECTIVE: It is important to prevent or slow the progression of prediabetes to
      type 2 diabetes and, therefore, reduce the risk of long-term complications. New
      therapeutic options will allow more patients to be effectively managed. Although
      theorized to be effective for prediabetes, dipeptidyl peptidase-4 (DPP-4)
      inhibitors have not been studied in this population. The purpose of this article
      is to report the results of a case in which a patient with prediabetes was
      treated with the DPP-4 inhibitor, sitagliptin. CASE SUMMARY: A 56-year-old woman
      was diagnosed with prediabetes at a hemoglobin A1C (A1C) of 6.2%. After 6 months
      of consistent lifestyle modifications, her A1C was 6.3%, and she wanted to start
      a medication to prevent disease progression. Because of anticipated risk or
      intolerability with standard prediabetes treatments, she was started on
      sitagliptin 100 mg daily; 6 weeks later, she noted improvements in glucometer
      readings. After 18 months on sitagliptin, her A1C had improved to 5.8% without
      further lifestyle improvements, and by 32 months, her A1C had improved to 5.6%.
      Her A1C was maintained within or below the prediabetes range of 5.7% to 6.4% over
      3 years of treatment with sitagliptin. DISCUSSION: Although human studies with
      DPP-4 inhibitors are lacking, the available studies have shown improvements in
      beta-cell function and postprandial and fasting glucose levels. Furthermore,
      animal studies have shown a delay in progression of prediabetes. No case reports
      have been found regarding DPP-4 inhibitor use in prediabetes. CONCLUSION:
      Sitagliptin may have a role in treating prediabetes and should be further
      studied.

PMID- 24676550
TI  - Vortioxetine for the treatment of depression.
AB  - OBJECTIVE: To evaluate the clinical literature and potential clinical role of
      vortioxetine (Brintellix) for the treatment of major depressive disorder (MDD).
      DATA SOURCES: A MEDLINE search (1966-February 2014) was conducted using the
      search terms vortioxetine, Lu AA21004, and depression. Bibliographies of all
      articles retrieved were also reviewed. All references included were published
      between 1999 and 2014. STUDY SELECTION/DATA EXTRACTION: All studies that included
      humans and were published in English, with data describing vortioxetine for the
      treatment of MDD, were reviewed. DATA SYNTHESIS: Vortioxetine is a novel
      multimodal antidepressant agent, which inhibits the 5-HT transporter protein,
      acts as a 5-HT3 antagonist, 5-HT1A receptor agonist, 5-HT7 receptor antagonist,
      and a partial agonist of the 5-HT1B receptor. It has been studied in 10 short
      term (6-8 weeks), 1 relapse-prevention, and 3 long-term extension trials.
      Vortioxetine demonstrated efficacy in reducing Montgomery-Asberg Depression
      Rating Scale or Hamilton Rating Scale for Depression scores in 6 of the short
      term trials. The proportion of individuals who responded to treatment and
      achieved remission increased over time in all 3 long-term trials. The most common
      adverse effects, consistently reported by >10% of individuals in the clinical
      trials include nausea and headache. CONCLUSIONS: Vortioxetine is an effective
      agent for the treatment of MDD, but it does not have any clear advantages over
      other available treatment options.

PMID- 24676551
TI  - [Schema therapy for personality disorders. A critical review].
AB  - In the 10 years since schema therapy was first recognized in Germany it has
      become widespread among practitioners and has taken a place among the so-called
      third wave therapies. The overall goal of schema therapy is conceptualizing and
      treating personality disorders or traits reinforcing axis I disorders. Early
      maladaptive schemas result from a child's unmet emotional core needs. In a
      limited reparenting therapy relationship these interpersonal situations are re
      experienced and rescripted under the therapist's control. Schema therapy
      integrates elements of existing models and techniques into a consistent case
      conceptualization as the bedrock for understanding and changing maladaptive
      coping behavior. This review article gives a comprehensive overview about the
      model, the therapy relationship and the application of the experiential
      techniques in relation to already developed approaches (including the current
      evidence). The strengths and weaknesses are briefly discussed. 

PMID- 24676553
TI  - Lignans and neolignans from the stems of Vibrunum erosum and their
      neuroprotective and anti-inflammatory activity.
AB  - A new lignan, (7'S,8S,8'S)-3,5'-dimethoxy-3',4,9'-trihydroxy-7',9-epoxy-8,8'
      lignan, named vibruresinol (1), was isolated from the stems of Viburnum erosum by
      silica gel, ODS, and Sephadex LH-20 column chromatography. In addition, four
      other known lignans, (7'R,8S,8'S)-3,5'-dimethoxy-3',4,8',9'-tetrahydroxy-7',9
      epoxy-8,8'-lignan (2), (+)-syringaresinol (3), (+)-pinoresinol (4), and (+)
      pinoresinol-4-O-beta-D-glucopyranoside (5), and five known neolignans, herpetol
      (6), vibsanol (7), (-)-dehydrodiconiferyl alcohol (8), icariside E4 (9), and
      dihydrodehydrodiconiferyl alcohol (10), were isolated in the same manner. The
      chemical structures of the compounds were determined based on spectroscopic data
      including NMR, MS, and IR. All of the compounds described above were isolated
      from V. erosum for the first time. The isolated compounds 3, 4, and 6 were
      evaluated for neuroprotective activity on glutamate-induced cell death in HT22
      cells and had EC50 values of 6.33 +/- 1.22, 6.96 +/- 0.65, and 9.15 +/- 0.36 MUM,
      respectively. Likewise, the same compounds had inhibitory activity on NO
      production in LPS-induced RAW 264.7 cells with IC50 values of 8.30 +/- 1.56, 7.89
      +/- 1.22, and 9.32 +/- 0.36 MUM, respectively. 

PMID- 24676552
TI  - Mitral valve repair versus replacement in patients with ischaemic mitral
      regurgitation and depressed ejection fraction: risk factors for early and mid
      term mortality?.
AB  - OBJECTIVES: Mitral valve (MV) surgery for ischaemic mitral regurgitation (IMR) in
      patients with depressed left ventricular ejection fraction (LVEF) is associated
      with poor outcomes. The optimal surgical strategy for IMR in these patients
      remains controversial. The objective of this study was to compare the early
      mortality and mid-term survival of MV repair versus MV replacement in patients
      with IMR and depressed LVEF undergoing coronary artery bypass grafting (CABG).
      METHODS: A retrospective, observational, cohort study was undertaken of
      prospectively collected data on 126 consecutive CABG patients with IMR and LVEF
      <40% undergoing either MV repair (n = 98, 78%) or MV replacement (n = 28, 22%)
      between July 2002 and February 2011. RESULTS: The overall mortality rate was 7.9%
      (n = 10). MV replacement was associated with a 4-fold increase in the risk of
      death compared with MV repair [17.9%, n = 5 vs 5.1%, n = 5; odds ratio (OR) 4.04,
      95% confidence interval (CI) 1.08-15.1, P = 0.04]. However, after adjusting for
      preoperative risk factors, the type of surgical procedure was not an independent
      risk factor for early mortality (OR 0.1, 95% CI 0.01-31, P = 0.7). Multivariable
      analysis showed that preoperative LVEF (OR 0.8, 95% CI 0.6-0.9, P = 0.018),
      preoperative B-type natriuretic peptide (BNP) levels (OR 1.01, 95% CI 1-1.02, P =
      0.025), preoperative left ventricle end-systolic diameter (OR 0.8, 95% CI 0.7
      1.0, P = 0.05) and preoperative left atrial diameter (OR 1.3, 95% CI 1.0-1.6, P =
      0.015) were independent risk factors of early mortality. At the median follow-up
      of 45 months (interquartile range 20-68 months), the mid-term survival rate was
      74% in the MV repair group and 70% in the MV replacement group (P = 0.08). At
      follow-up, predictors of worse survival were BNP levels [hazard ratio (HR) 1.0,
      95% CI 1.0-1.01, P = 0.047], preoperative renal failure (HR 4.6, 95% CI 1.1-20.3,
      P = 0.039) and preoperative atrial fibrillation (HR 3.3, 95% CI 1.1-10, P =
      0.032). CONCLUSIONS: MV repair in CABG patients with IMR and depressed LVEF is
      not superior to MV replacement with regard to operative early mortality and mid
      term survival.

PMID- 24676554
TI  - STAT3 inhibitor WP1066 attenuates miRNA-21 to suppress human oral squamous cell
      carcinoma growth in vitro and in vivo.
AB  - Abnormalities in signal transducer and activator of transcription 3 (STAT3) are
      involved in the oncogenesis of oral squamous cell carcinoma (OSCC). MicroRNA-21
      (miR-21) is an important gene expression regulator to OSCC. miR-21 induction by
      STAT3 has been reported in multiple human cancers. In the present study, we found
      that STAT3 (-/p) expression was positively correlated with miR-21 in 60 OSCC
      samples. A reporter gene assay showed that miR-21 overexpression was dependent on
      STAT3 activation. WP1066, a small molecular inhibitor of STAT3, was used to
      suppress STAT3 expression in OSCC cells. TSCCA and TCA8113 showed reduction in
      tumor cell proliferation, invasion ability and miR-21 expression by WP1066
      treatment. In addition, the expression of miR-21 target proteins [programmed cell
      death 4 (PDCD4), tissue inhibitor of metalloproteinase 3 (TIMP-3) and phosphatase
      and tensin homolog (PTEN)] was upregulated. Restored STAT3 expression by IL-6
      induced miR-21 overexpression, which further confirmed the correlation between
      STAT3 and miR-21. WP1066 inhibited tumor growth and induced tumor cell apoptosis
      in the TSCCA xenograft tumor model. Western blotting and immunohistochemistry
      staining indicated that STAT3 (-/p), Ki67, Bcl-2 and MMP-2 expressions decreased
      in the WP1066-treated group; PDCD4, TIMP-3 and PTEN expression increased simulta
      neously. The present study provides evidence that targeting STAT3 could regulate
      OSCC cell growth in a miR-21-dependent manner and WP1066 could be a novel
      candidate drug to treat OSCC by inhibiting STAT3/miR-21 axis.

PMID- 24676555
TI  - Haemangioma family burden: creation of a specific questionnaire.
AB  - To develop and validate a specific questionnaire to assess burden on families of
      children with infantile haemangioma (IH): the Haemangioma Family Burden
      questionnaire (HFB). Items were generated from a literature review and a verbatim
      report from parents. Subsequently, a study was implemented at the Necker Hospital
      and the Pellegrin Children's Hospital for psychometric analysis. The HFB was
      refined via item reduction according to inter-question correlations, consensus
      among experts and exploratory factor analysis. A 20-item questionnaire, grouped
      into 5 dimensions, was obtained. Construct validity was demonstrated and HFB
      showed good internal coherence (Cronbach's alpha: 0.93). The HFB was
      significantly correlated with the mental dimension of the Short-Form-12 (r = 
      0.75), and the Psychological General Well-Being Index (r = -0.61). HFB scores
      differed significantly according to the size and localization of the IH. A
      validated tool for assessing the burden on families of children with IH is now
      available. 

PMID- 24676556
TI  - A two-dimensional homospin Cu(II) ferrimagnet featuring S-shaped hexanuclear
      secondary building blocks.
AB  - The decomposition of 2-(1-hydroxy-2-methylpropan-2-yl-imino)-1,2-diphenylethanone
      in the presence of copper acetate promoted the formation of a two-dimensional
      homospin Cu(II) ferrimagnet featuring S-shaped hexanuclear secondary building
      blocks and a new pentanodal topology.

PMID- 24676557
TI  - General physical health advice for people with serious mental illness.
AB  - BACKGROUND: There is currently much focus on provision of general physical health
      advice to people with serious mental illness and there has been increasing
      pressure for services to take responsibility for providing this. OBJECTIVES: To
      review the effects of general physical healthcare advice for people with serious
      mental illness. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's
      Trials Register (last update search October 2012) which is based on regular
      searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO and
      registries of Clinical Trials. There is no language, date, document type, or
      publication status limitations for inclusion of records in the register.
      SELECTION CRITERIA: All randomised clinical trials focusing on general physical
      health advice for people with serious mental illness.. DATA COLLECTION AND
      ANALYSIS: We extracted data independently. For binary outcomes, we calculated
      risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat
      basis. For continuous data, we estimated the mean difference (MD) between groups
      and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk
      of bias for included studies and created 'Summary of findings' tables using
      GRADE. MAIN RESULTS: Seven studies are now included in this review. For the
      comparison of physical healthcare advice versus standard care we identified six
      studies (total n = 964) of limited quality. For measures of quality of life one
      trial found no difference (n = 54, 1 RCT, MD Lehman scale 0.20, CI -0.47 to 0.87,
      very low quality of evidence) but another two did for the Quality of Life Medical
      Outcomes Scale - mental component (n = 487, 2 RCTs, MD 3.70, CI 1.76 to 5.64).
      There was no difference between groups for the outcome of death (n = 487, 2 RCTs,
      RR 0.98, CI 0.27 to 3.56, low quality of evidence). For service use two studies
      presented favourable results for health advice, uptake of ill-health prevention
      services was significantly greater in the advice group (n = 363, 1 RCT, MD 36.90,
      CI 33.07 to 40.73) and service use: one or more primary care visit was
      significantly higher in the advice group (n = 80, 1 RCT, RR 1.77, CI 1.09 to
      2.85). Economic data were equivocal. Attrition was large (> 30%) but similar for
      both groups (n = 964, 6 RCTs, RR 1.11, CI 0.92 to 1.35). Comparisons of one type
      of physical healthcare advice with another were grossly underpowered and
      equivocal. AUTHORS' CONCLUSIONS: General physical health could lead to people
      with serious mental illness accessing more health services which, in turn, could
      mean they see longer-term benefits such as reduced mortality or morbidity. On the
      other hand, it is possible clinicians are expending much effort, time and
      financial resources on giving ineffective advice. The main results in this review
      are based on low or very low quality data. There is some limited and poor quality
      evidence that the provision of general physical healthcare advice can improve
      health-related quality of life in the mental component but not the physical
      component, but this evidence is based on data from one study only. This is an
      important area for good research reporting outcome of interest to carers and
      people with serious illnesses as well as researchers and fundholders.

PMID- 24676558
TI  - A novel microchannel-based device to capture and analyze circulating tumor cells
      (CTCs) of breast cancer.
AB  - Circulating tumor cells (CTCs) have been shown in many studies as a possible
      biomarker for metastasis and may be instrumental for the spread of the disease.
      Despite advances in CTC capturing technologies, the low frequency of CTCs in
      cancer patients and the heterogeneity of the CTCs have limited the wide
      application of the technology in clinic. In this study, we investigated a novel
      microfluidic technology that uses a size- and deformability-based capture system
      to characterize CTCs. This unique platform not only allows flexibility in the
      selection of antibody markers but also segregates the CTCs in their own chambers,
      thus, enabling morphological, immunological and genetic characterization of each
      CTC at the single cell level. In this study, different breast cancer cell lines
      including MCF7, MDA-MB-231 and SKBR3, as well as a panel of breast cancer
      biomarkers were used to test the device. The technology can capture a wide range
      of cells with high reproducibility. The capturing efficiency of the cells is
      greater than 80%. In addition, the background of leukocytes is minimized because
      individual cells are segregated in their own chambers. The device captured both
      epithelial cancer cells such as MCF7 and SKBR3 and mesenchymal cells such as MDA
      MB-231. Immunostaining of the captured cells on the microchannel device suggests
      that a panel of breast cancer biomarkers can be used to further characterize
      differential expression of the captured cells. 

PMID- 24676559
TI  - The HIV epidemic in Southern Africa - Is an AIDS-free generation possible?
AB  - Southern Africa, home to about 20 % of the global burden of infection continues
      to experience high rates of new HIV infection despite substantial programmatic
      scale-up of treatment and prevention interventions. While several countries in
      the region have had substantial reductions in HIV infection, almost half a
      million new infections occurred in this region in 2012. Sexual transmission
      remains the dominant mode of transmission. A recent national household survey in
      Swaziland revealed an HIV prevalence of 14.3 % among 18-19 year old girls,
      compared to 0.8 % among their male peers. Expanded ART programmes in Southern
      Africa have resulted in dramatically decreased HIV incidence and HIV mortality
      rates. In South Africa alone, it is estimated that more than 2.1 million of the
      6.1 million HIV-positive people were receiving ART by the end of 2012, and that
      this resulted in more than 2.7 million life-years saved, and hundreds of
      thousands of HIV infections averted. Biological, behavioural and structural
      factors all contribute to the ongoing high rates of new HIV infection; however,
      as the epidemic matures and mortality is reduced from increased ART coverage,
      epidemiological trends become hard to quantify. What is clear is that a key
      driver of the Southern African epidemic is the high incidence rate of infection
      in young women, a vulnerable population with limited prevention options.
      Moreover, whilst ongoing trials of combination prevention, microbicides and
      behavioural economics hold promise for further epidemic control, an AIDS-free
      generation will not be realised unless incident infections in key populations are
      reduced.

PMID- 24676560
TI  - Patients with renal artery stenosis may not be suitable for renal denervation.

PMID- 24676561
TI  - A novel synthetic approach to the bicyclo[5.3.1]undecan-11-one framework of
      vinigrol.
AB  - The first synthetic attempt commencing from an eight-membered ring to approach
      the [5.3.1] bicyclic core of vinigrol has demonstrated the feasibility of using
      the conformational bias of the cyclooctane-ring system to realize highly
      diastereoselective reactions. The synthetic potential of the newly disclosed
      access to in/out isomerism may stimulate broader interests. 

PMID- 24676562
TI  - Association Splitting: feasibility study of a novel technique to reduce weight
      and shape concerns.
AB  - Weight and shape concerns are core aspects of eating disorders and can have an
      intrusive and obsessive character. Such thoughts play an important role in the
      development and maintenance of eating disorders and seem to be a result of
      dysfunctional cognitive networks. Association Splitting, a novel intervention for
      obsessive-compulsive disorders, targets such dysfunctional networks. AIMS: To
      adapt Association Splitting for the reduction of weight- and shape-related
      cognitions in students with high weight and shape concerns. METHODS: Thirteen
      students with high weight and shape concerns were recruited and ten completed
      assessments before and after using the Association Splitting approach. Self
      reported weight and shape concerns, eating behaviours and obsessive thinking were
      assessed. Changes between the two time points were analysed. RESULTS: After using
      Association Splitting, participants reported lower weight and shape concerns,
      reduced drive for thinness and body dissatisfaction and lower levels of eating
      disorder-related behaviours. The technique was perceived as helpful by 70% of the
      participants. CONCLUSION: Association Splitting is a feasible approach to
      reducing weight and shape concerns and might be a useful addition to the
      treatment or prevention of eating disorders.

PMID- 24676564
TI  - Antenatal taurine supplementation increases taurine content in intrauterine
      growth restricted fetal rat brain tissue.
AB  - This study aimed to determine the influence of antenatal taurine supplementation
      on taurine content in the brains of fetal rats with intrauterine growth
      restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi
      Children's Hospital Affiliated to Beijing Military General Hospital in China from
      January to June 2013. Fifteen pregnant rats were randomly divided into three
      groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement
      group (Taurine group) (n = 5). The IUGR model was induced using a low-protein
      diet throughout gestation. Rats in the taurine group were fed a diet supplemented
      with 300 mg/kg/day taurine for 12 days after conception until natural delivery.
      Two fetal rats were randomly selected in every litter, and taurine levels in the
      brains of rats were detected using high-performance liquid chromatography-mass
      spectrometry. Results showed that (1) the mean body weight of the fetal rats in
      the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619
      +/- 0.4132, 4.509 +/- 0.454, and 5.176 +/- 0.436 g (F = 429.818, P < 0.01),
      respectively, and (2) that taurine levels in the brains of the fetal rats in the
      normal control, IUGR and taurine groups were (2.399 +/- 0.134) * 10(5), (1.881 +/
      0.166) * 10(5) and (2.170 +/- 0.191) * 10(5) MUg/g (F = 24.828, P < 0.01),
      respectively. Overall, our results indicated that taurine levels in IUGR fetal
      rat brains were lower than in the control animals, and that antenatal taurine
      supplementation could significantly increase taurine levels in the brains of
      fetal rats with IUGR.

PMID- 24676565
TI  - Association between common genetic variants of alpha2A-, alpha2B- and alpha2C
      adrenoceptors and the risk of silent brain infarction.
AB  - Silent brain infarction (SBI) is an asymptomatic cerebrovascular disorder. The
      aim of the present study was to investigate the association between adrenoceptor
      alpha2 (ADRA2) gene polymorphisms and SBI. A total of 361 patients with SBI and
      467 healthy control subjects were examined. The polymerase chain reaction was
      performed to genotype the ADRA2A 1780G>A, ADRA2B 301-303 insertion/deletion (I/D)
      and ADRA2C 322-325I/D polymorphisms. The frequency of the ADRA2C 322-325I/D
      polymorphism was significantly different between patients with SBI and control
      subjects. When interaction analyses were performed for vascular risk factors, the
      ADRA2C 322-325ID genotype increased the risk for SBI in the presence of
      hypertension and elevated plasma homocysteine levels. The ADRA2C 322-325ID
      genotype and plasma homocysteine levels showed a significant synergistic effect
      for SBI. In addition, the ADRA2A 1780AA genotype was associated with elevated
      plasma homocysteine levels. Although further analysis of the association between
      ADRA2 polymorphisms and clinical risk factors of SBI is required, the present
      study of a limited set of SBI risk factors with ADRA2 polymorphisms provides the
      first evidence of the involvement of ADRA2 gene family members in the development
      of SBI. Further studies using larger and more heterogeneous populations are
      required to validate the association of ADRA2 polymorphisms with SBI.

PMID- 24676563
TI  - In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in
      animals and humans.
AB  - Glycogen serves as an important energy reservoir in the human body. Despite the
      abundance of glycogen in the liver and skeletal muscles, its concentration in the
      brain is relatively low, hence its significance has been questioned. A major
      challenge in studying brain glycogen metabolism has been the lack of availability
      of non-invasive techniques for quantification of brain glycogen in vivo. Invasive
      methods for brain glycogen quantification such as post mortem extraction
      following high energy microwave irradiation are not applicable in the human
      brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has
      been possible to measure brain glycogen concentrations and turnover in
      physiological conditions, as well as under the influence of stressors such as
      hypoglycemia and visual stimulation. This review presents an overview of the
      principles of the (13)C MRS methodology and its applications in both animals and
      humans to further our understanding of glycogen metabolism under normal
      physiological and pathophysiological conditions such as hypoglycemia unawareness.

PMID- 24676566
TI  - Use of flexible ureteroscopy in the clinical practice for the treatment of renal
      stones: results from a large European survey conducted by the EAU Young Academic
      Urologists-Working Party on Endourology and Urolithiasis.
AB  - Treatment of renal stones using flexible ureteroscopy (fURS) is increasingly
      common despite the poor evidence in literature supporting its use and
      indications. With this study, we wanted to investigate the current use and
      indication of fURS for the treatment of renal stones in the clinical practice
      across the European countries. A survey was conducted using an emailed
      questionnaire consisting of 21 items; 2,894 recipients were selected via the EAU
      membership database. The questionnaires were collected through the SurveyMonkey
      system and the data were processed with the SPSS statistical package.
      Frequencies, cross tabs and Pearson correlation coefficients were applied as
      appropriate. 1,168 questionnaires were collected (response rate 40.4%). fURS was
      performed in 72.9% of the respondents' institutions, and 54.2% of the respondents
      were performing the procedure. For 95% of the users, fURS was considered first
      line treatment, for stone of lower pole stone (45.9%) and <1 cm (44.2%) and 2 cm
      (43.8%) in size. The ureteral access sheaths were used routinely by more than 70%
      of the respondents. Lower pole stone repositioning technique was routinely
      performed by 45.9% of the surgeons. After fragmentation, 47.2% of the responders
      preferred to retrieve only the bigger fragments. At the end of fURS, lower volume
      surgeons were more likely to place routinely a double-J stent (p = 0.001). Higher
      volume surgeons estimated a higher durability of devices, both optical and
      digital ones (p < 0.001), and were more prone to consider fURS cost-effective
      when compared to other treatment modalities (p < 0.001). fURS is widely used for
      the treatment of renal stones and its use and indication can vary according to
      the age and surgeons' case volume. Higher volume surgeons are more prompt to
      extend international guidelines indications and to consider the technology cost
      effective.

PMID- 24676567
TI  - Criteria for solvate ionic liquids.
AB  - Certain concentrated mixtures of salts and solvents are not simply "solutions"
      anymore, but they may be described as "ionic liquids". In this perspective paper,
      we describe possible criteria for the new family of ionic liquids: "solvate"
      ionic liquids. This subclass of ionic liquids was originally proposed by Angell
      et al. in their recent review; however, their criteria remain to be debated.
      Concentrated mixtures of lithium salts and organic solvents are useful models for
      these solvate ionic liquids, and the effects of the salt concentration, types of
      solvents, and counter anions of the lithium salts on their structure and
      properties have been explored to enable contrast with traditional solutions, and
      to help determine whether a given mixture belongs to the solvate ionic liquid or
      not. 

PMID- 24676568
TI  - Characterization of two cases of bullous pemphigoid reactive only with BP230 on
      Japanese enzyme-linked immunosorbent assays.

PMID- 24676570
TI  - Purification and characterization of pepsin-solubilized collagen from skin of sea
      cucumber Holothuria parva.
AB  - Pepsin-solubilized collagen (PSC) was extracted from the skin of sea cucumber
      Holothuria parva and was fractionally characterized. The PSC from H. parva skin
      consisted of three alpha1 chains (alpha1)3, in contrast to calf skin collagen
      type I with two alpha1 and one alpha2 chains (alpha1)2alpha2 with approximately
      130 kDa each. The maximum transition (Tm) and denaturation temperature (Td) of
      PSC were determined to be 46.94 and 32.5  degrees C, respectively. The amino acid
      composition analysis revealed that glycine, proline, alanine, and hydroxyproline
      were the abundant amino acids available in extracted PSC. The results showed that
      the isolated collagen from H. parva has some similar characteristics to
      previously reported collagens used in food and pharmaceutical industries. 

PMID- 24676571
TI  - Enhanced lipid production by co-cultivation and co-encapsulation of oleaginous
      yeast Trichosporonoides spathulata with microalgae in alginate gel beads.
AB  - This study attempted to enhance biomass and lipid productivity of an oleaginous
      yeast Trichosporonoides spathulata by co-culturing with microalgae Chlorella
      spp., optimizing culture conditions, and encapsulating them in alginate gel
      beads. The co-culture of the yeast with microalgae Chlorella vulgaris var.
      vulgaris TISTR 8261 most enhanced overall biomass and lipid productivity by 1.6
      fold of the yeast pure culture at 48 h and by 1.1-fold at 72 h. After
      optimization and scale-up in a bioreactor, this co-culture produced the highest
      biomass of 12.2 g/L with a high lipid content of 47 %. The dissolved oxygen
      monitoring system in the bioreactor showed that the microalgae worked well as an
      oxygen supplier to the yeast. This study also showed that the co-encapsulated
      yeast and microalgae could grow and produce lipid as same as their free cells
      did. Therefore, it is possible to apply this encapsulation technique for lipid
      production and simplification of downstream harvesting process. This co-culture
      system also produced the lipid with high content of saturated fatty acids,
      indicating its potential use as biodiesel feedstock with high oxidative
      stability.

PMID- 24676572
TI  - Multivariate pattern recognition for diagnosis and prognosis in clinical
      neuroimaging: state of the art, current challenges and future trends.
AB  - Many diseases are associated with systematic modifications in brain morphometry
      and function. These alterations may be subtle, in particular at early stages of
      the disease progress, and thus not evident by visual inspection alone. Group
      level statistical comparisons have dominated neuroimaging studies for many years,
      proving fascinating insight into brain regions involved in various diseases.
      However, such group-level results do not warrant diagnostic value for individual
      patients. Recently, pattern recognition approaches have led to a fundamental
      shift in paradigm, bringing multivariate analysis and predictive results, notably
      for the early diagnosis of individual patients. We review the state-of-the-art
      fundamentals of pattern recognition including feature selection, cross-validation
      and classification techniques, as well as limitations including inter-individual
      variation in normal brain anatomy and neurocognitive reserve. We conclude with
      the discussion of future trends including multi-modal pattern recognition, multi
      center approaches with data-sharing and cloud-computing. 

PMID- 24676573
TI  - Novel surfactant-free route to delaminated all-silica and titanosilicate zeolites
      derived from a layered borosilicate MWW precursor.
AB  - Layered borosilicate zeolite precursor ERB-1P (Si/B = 11) is delaminated via
      simultaneous deboronation and SDA removal, to yield material DZ-1 consisting of
      silanol nests, using a simple aqueous Zn(NO3)2 treatment. Characterization of
      this synthesis process by PXRD shows loss of long-range order, and transmission
      electron microscopy (TEM) demonstrates transformation of rectilinear layers in
      the layered zeolite precursor to single and curved layers in the delaminated
      material. N2 physisorption confirms the expected decrease of micropore volume and
      increase in external surface area for delaminated materials relative to their
      calcined 3D zeolite counterpart. Elemental analysis shows loss of B and absence
      of Zn in the delaminated material. Resonances corresponding to silanol nests are
      evident via (29)Si solid-state NMR spectroscopy in DZ-1, which should be located
      within 12-MR pockets near the external surface. We have successfully utilized
      these nests as tetrahedral recognition sites for incorporation of Ti within an
      isolated framework coordination environment in material Ti-DZ-1. Diffuse
      reflectance ultraviolet (DR-UV) spectroscopy of Ti-DZ-1 confirms isolated
      framework Ti sites, which are assigned to bands in the range of 210 nm-230 nm.
      Infrared spectra of Ti-DZ-1 consist of a distinct absorption band at 960 cm(-1),
      which is absent in DZ-1 prior to Ti incorporation and has been previously
      correlated with the presence of framework Ti species. Infrared spectra after
      pyridine adsorption demonstrate bands consistent with Lewis-acid sites in the
      resulting Ti-substituted delaminated zeolite. The accessibility of these Lewis
      acid sites is confirmed when using Ti-DZ-1 as a catalyst for cyclohexene
      epoxidation using tert-butyl hydroperoxide as the organic oxidant - a reaction
      for which both DZ-1 and TS-1 are inactive.

PMID- 24676574
TI  - Performance traits and immune response of broiler chicks treated with zinc and
      ascorbic acid supplementation during cyclic heat stress.
AB  - This research was conducted to investigate the effect of supplementation of zinc
      (Zn) and ascorbic acid (AA) in heat-stressed broilers. A total of 160-day-old
      broiler chicks of approximately the same weight and appearance were divided into
      four treatment groups (control, T1, T2, and T3). Control group was fed a standard
      diet without any supplementation. T1 was supplemented with Zn at the rate of 60
      mg/kg of feed, T2 was supplemented with 300 mg/kg of feed AA, and T3 was
      supplemented with combination of Zn and AA. From week 3 to 5, heat stress
      environment was provided at the rate of 12 h at 25  degrees C, 3 h at 25 to 34 
      degrees C, 6 h at 34  degrees C, and 3 h at 34 to 25  degrees C daily. The
      results revealed that feed intake, body weight and feed conversion ratio (FCR),
      and weight of thymus, spleen, and bursa of Fabricius improved significantly (P <
      0.05) in T3 compared to the other treatments. Antibody titer against Newcastle
      disease (ND), infectious bursal disease (IBD), and infectious bronchitis (IB)
      increased significantly (P < 0.05) in T2 and T3 groups. However, total leucocytes
      count, lymphocytes, and monocytes increased (P < 0.05) in all treated groups
      compared to control. The results indicated that the supplementation of Zn or AA
      alone or in combination improved the performance and immune status of broilers
      reared under heat stress.

PMID- 24676575
TI  - From Amazon rain forest flora to the state-of-the-art technology devices, the
      incessant search for 'magic bullets' against Streptococcus mutans.

PMID- 24676576
TI  - The susceptibility of Streptococcus mutans to antibacterial photodynamic therapy:
      a comparison of two different photosensitizers and light sources.
AB  - Streptococcus mutans is the main etiological agent for dental caries. Recently,
      photodynamic therapy (PDT) has been introduced as a new modality in bacterial
      decontamination. OBJECTIVE: This in vitro study was carried out to evaluate the
      susceptibility of Streptococcus mutans to antibacterial PDT using two different
      photosensitizers and light sources. MATERIAL AND METHODS: Standard suspensions of
      S. mutans were exposed to laser light at 662 nm and Radachlorin or LED 630 nm in
      combination with Toluidine blue O (TBO). Radiation-only groups, photosensitizer
      alone, and groups with no treatment were used as controls. Bacterial suspension
      from each treatment was subcultured onto the surface of Mueller-Hinton agar
      plates and bacterial growth was assessed. The results were analyzed by analysis
      of variance and Tukey test (p<0.05). RESULTS: PDT with TBO and Radachlorin(r)
      significantly reduced S. mutans viability, whereas no difference was observed
      between two groups of PDT. In the groups treated just with the photosensitizer or
      irradiated alone, no significant reduction of S. mutans colonies was observed.
      CONCLUSION: S. mutans colonies were susceptible to either 662 nm laser or LED
      light in the presence of Radachlorin and TBO respectively with no priority.

PMID- 24676577
TI  - Micro-shear bond strength and surface micromorphology of a feldspathic ceramic
      treated with different cleaning methods after hydrofluoric acid etching.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of feldspathic
      ceramic surface cleaning on micro-shear bond strength and ceramic surface
      morphology. MATERIAL AND METHODS: Forty discs of feldspathic ceramic were
      prepared and etched with 10% hydrofluoric acid for 2 minutes. The discs were
      randomly distributed into five groups (n=8): C: no treatment, S: water spray +
      air drying for 1 minute, US: immersion in ultrasonic bath for 5 minutes, F:
      etching with 37% phosphoric acid for 1 minute, followed by 1-minute rinse, F+US:
      etching with 37% phosphoric acid for 1 minute, 1-minute rinse and ultrasonic bath
      for 5 minutes. Composite cylinders were bonded to the discs following application
      of silane and hydrophobic adhesive for micro-shear bond strength testing in a
      universal testing machine at 0.5 mm/min crosshead speed until failure.
      Stereomicroscopy was used to classify failure type. Surface micromorphology of
      each treatment type was evaluated by scanning electron microscopy at 500 and
      2,500 times magnification. RESULTS: One-way ANOVA test showed no significant
      difference between treatments (p=0.3197) and the most common failure types were
      cohesive resin cohesion followed by adhesive failure. Micro-shear bond strength
      of the feldspathic ceramic substrate to the adhesive system was not influenced by
      the different surface cleaning techniques. Absence of or less residue was
      observed after etching with hydrofluoric acid for the groups US and F+US.
      CONCLUSIONS: Combining ceramic cleaning techniques with hydrofluoric acid etching
      did not affect ceramic bond strength, whereas, when cleaning was associated with
      ultrasound, less residue was observed.

PMID- 24676578
TI  - Anti-Streptococcal activity of Brazilian Amazon Rain Forest plant extracts
      presents potential for preventive strategies against dental caries.
AB  - Caries is a global public health problem, whose control requires the introduction
      of low-cost treatments, such as strong prevention strategies, minimally invasive
      techniques and chemical prevention agents. Nature plays an important role as a
      source of new antibacterial substances that can be used in the prevention of
      caries, and Brazil is the richest country in terms of biodiversity. OBJECTIVE: In
      this study, the disk diffusion method (DDM) was used to screen over 2,000
      Brazilian Amazon plant extracts against Streptococcus mutans. MATERIAL AND
      METHODS: Seventeen active plant extracts were identified and fractionated.
      Extracts and their fractions, obtained by liquid-liquid partition, were tested in
      the DDM assay and in the microdilution broth assay (MBA) to determine their
      minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations
      (MBCs). The extracts were also subjected to antioxidant analysis by thin layer
      chromatography. RESULTS: EB271, obtained from Casearia spruceana, showed
      significant activity against the bacterium in the DDM assay (20.67+/-0.52 mm), as
      did EB1129, obtained from Psychotria sp. (Rubiaceae) (15.04+/-2.29 mm). EB1493,
      obtained from Ipomoea alba, was the only extract to show strong activity against
      Streptococcus mutans (0.08 mg/mL<MIC<0.16 mg/mL; MBC=0.16 mg/mL) in the MBA.
      CONCLUSIONS: The active extracts, discovered in the Amazon rain forest, show
      potential as sources of new antibacterial agents for use as chemical coadjuvants
      in prevention strategies to treat caries.

PMID- 24676579
TI  - Apical transportation associated with ProTaper Universal F1, F2 and F3
      instruments in curved canals prepared by undergraduate students.
AB  - OBJECTIVE: This study evaluated apical transportation associated with ProTaper
      Universal Fl, F2 and F3 rotary files in curved canais prepared by undergraduate
      students. MATERIAL AND METHODS: Twenty mesial roots of mandibular molars with
      curvatures ranging between 25 degrees  and 35 degrees  were selected. Mesiobuccal
      canals were instrumented by twenty students with the ProTaper system (Dentsply
      Maillefer, Ballaigues, Switzerland) according to the manufacturer's instructions.
      Pre-fiaring was performed with Sl and SX files. A #15 K-file was inserted into
      the root canal up to the working length (WL), and an initial digital radiograph
      was taken in a buccolingual direction (baseline). Afterwards, the S1, S2, F1, F2,
      and F3 files were employed up to the WL. Other radiographies were taken in the
      same orientation of the baseline after the use of the Fl, F2, and F3 files, with
      each file inserted into the root canal. The radiographic images were overlapped,
      and the Image J software was used to measure the distance between the rotary
      files' ends and the #15 K-file's end, characterizing the apical transportation.
      Data were analyzed by Repeated Measure ANOVA and by the SNK post hoc test
      (P<0.05). RESULTS: It was verified that file size affected apical transportation
      significantly (P<0.001). The F3 file showed higher apical transportation than Fl
      and F2, while between these last files there was no difference. CONCLUSION: The
      undergraduate students produced lower apical transportation in curved canals when
      they did not use the F3 rotary file.

PMID- 24676580
TI  - Serum levels of inflammatory markers in type 2 diabetes patients with chronic
      periodontitis.
AB  - Diabetes has been associated with periodontitis, but the mechanisms through which
      periodontal diseases affect the metabolic control remain unclear. OBJECTIVE: This
      study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and
      monocyte chemoattractant protein 1 (MCP-1), in type 2 diabetic patients in the
      presence of chronic periodontitis. MATERIAL AND METHODS: Forty two individuals
      were enrolled in this study and assigned to one of five groups: diabetes mellitus
      with inadequate glycemic control and periodontitis (DMI+P, n = 10), diabetes
      mellitus with adequate glycemic control and periodontitis (DMA+P, n = 10),
      diabetes mellitus without periodontitis (DM, n = 10), periodontitis without
      diabetes (P, n=6), and neither diabetes nor periodontitis (H, n = 6). Periodontal
      clinical examination included visible plaque index (PL), gingival bleeding index
      (GB), probing depth (PD), attachment level (AL) and bleeding on probing (BP).
      Glycemic control was evaluated by serum concentration of glycated hemoglobin
      (HbAlc). Inflammatory serum markers IL-8, IL-6 and (MCP-1) were measured by
      ELISA. RESULTS: DMI+P and DMA+P groups presented higher PD (p=0.025) and AL
      (p=0.003) values when compared to the P group. There were no significant
      differences among groups for IL-6, IL-8 and MCP-1 serum levels. CONCLUSIONS:
      Although periodontitis was more severe in diabetic patients, the serum levels of
      the investigated inflammatory markers did not differ among the groups.

PMID- 24676581
TI  - Transition temperature range of thermally activated nickel-titanium archwires.
AB  - OBJECTIVES: The shape memory resulting from the superelasticity and thermoelastic
      effect is the main characteristic of thermally activated NiTi archwires and is
      closely related to the transition temperature range (TTR). The aim of this study
      was to evaluate the TTR of thermally activated NiTi archwires commercially
      available. MATERIAL AND METHODS: Seven different brands of 0.019" x 0.025"
      thermally activated nickel-titanium archwires were tested as received by
      differential scanning calorimetry (DSC) over the temperature range from -100 
      degrees C to 150  degrees C at 10  degrees C/min. RESULTS: All thermally
      activated NiTi archwires analyzed presented stage transformation during thermal
      scanning with final austenitic temperature (Af) ranging from 20.39  degrees C to
      45.42  degrees C. Three brands of NiTi archwires presented Af close to the room
      temperature and, this way, do not present properties of shape memory and
      pseudoelasticity that are desirable in clinical applications. CONCLUSIONS: The
      thermally activated NiTi archwires present great variability in the TTR and the
      elastic parameters of each NiTi archwire should be provided by the manufacturers,
      to allow achievement of the best clinical performance possible.

PMID- 24676582
TI  - Bacteriological analysis of necrotic pulp and fistulae in primary teeth.
AB  - OBJECTIVES: Primary teeth work as guides for the eruption of permanent dentition,
      contribute for the development of the jaws, chewing process, preparing food for
      digestion, and nutrient assimilation. Treatment of pulp necrosis in primary teeth
      is complex due to anatomical and physiological characteristics and high number of
      bacterial species present in endodontic infections. The bacterial presence alone
      or in association in necrotic pulp and fistula samples from primary teeth of boys
      and girls was evaluated. MATERIAL AND METHODS: Necrotic pulp (103) and fistula
      (7) samples from deciduous teeth with deep caries of 110 children were evaluated.
      Bacterial morphotypes and species from all clinical samples were determined.
      RESULTS: A predominance of gram-positive cocci (81.8%) and gram-negative
      coccobacilli (49.1%) was observed. In 88 out of 103 pulp samples, a high
      prevalence of Enterococcus spp. (50%), Porphyromonas gingivalis (49%),
      Fusobacterium nucleatum (25%) and Prevotella nigrescens (11.4%) was observed.
      Porphyromonas gingivalis was detected in three out of seven fistula samples,
      Enterococcus spp. in two out of seven samples, and F. nucleatum, P. nigrescens
      and D. pneumosintes in one out of seven samples. CONCLUSIONS: Our results show
      that Enterococcus spp. and P. gingivalis were prevalent in necrotic pulp from
      deciduous teeth in boys from 2 to 5 years old, and that care of the oral cavity
      of children up to five years of age is important.

PMID- 24676583
TI  - The impact of the addition of iodoform on the physicochemical properties of an
      epoxy-based endodontic sealer.
AB  - Due to the low radiopacity of Sealer 26, iodoform is frequently empirically added
      to this sealer. Thus, the interference of this procedure with the physicochemical
      properties of Sealer 26 must be evaluated. OBJECTIVE: This study evaluated the
      influence of the addition of iodoform on setting time, flow, solubility, pH, and
      calcium release of an epoxy-based sealer. MATERIAL AND METHODS: The control group
      was pure Sealer 26, and the experimental groups were Sealer 26 added with 1.1 g,
      0.55 g or 0.275 g of iodoform. Setting time evaluation was performed in
      accordance with the ASTM C266-03 speciflcation. The analysis of flow and
      solubility was in accordance with the ISO 6876-2001 speciflcation. For the
      evaluation of pH and calcium ion release, polyethylene tubes were filled with the
      materials and immersed in flasks with 10 ml of deionized water. After 24 h, 7,
      14, 21, 28, and 45 days pH was measured. In 45 days, the calcium released was
      evaluated with an atomic absorption spectrophotometer. RESULTS: The addition of
      iodoform increased setting time in comparison with pure sealer (P<0.05). As for
      flow, solubility, and calcium release, the mixtures presented results similar to
      pure sealer (p>0.05). In the 24 h period, the mixture with 1.1 g and 0.55 g of
      iodoform showed lower pH than pure sealer and than sealer added with 0.275 g of
      iodoform (P<0.05). CONCLUSIONS: The iodoform added to Sealer 26 interferes with
      its setting time and solubility properties. Further studies are needed to address
      the clinical signiflcance of this interference.

PMID- 24676584
TI  - FASN expression, angiogenesis and lymphangiogenesis in central and peripheral
      giant cell lesions.
AB  - Central giant cell lesion (CGCL) and peripheral giant cell lesion (PGCL) are non
      neoplastic proliferative processes of the jaws. PGCL is a reactive process
      induced by irritant local factors and CGCL is an intra-osseous lesion of unknown
      etiology. Both lesions exhibit similar histologic features showing abundant
      mononuclear cells, admixed with a large number of multinucleated giant cells and
      a rich vascularized stroma with extravasated erythrocytes, hemosiderin
      deposition, and blood-filled pools. Recent studies have linked fatty acid
      synthase (FASN) with angiogenesis. OBJECTIVE: To evaluate angiogenesis and
      lymphangiogenesis and their relationship with FASN expression in CGCL and PGCL.
      MATERIAL AND METHODS: Thirteen CGCL and 14 PGCL of the jaws were selected for
      immunoexpression of FASN; CD34 and CD105 (to assess blood microvessel density
      [MVD] and microvessel area [MVA]); and D2-40 (to assess lymphatic MVD and MVA).
      RESULTS: Within PGCL and CGCL, MVD-CD34 was signifcantly higher than MVD-CD10S,
      followed by MVD-D2-40. Moreover, a signifcantly higher number of FASN-positive
      multinucleated giant cells than mononuclear cells were observed. Between PGCL and
      CGCL, only MVD-CD34 and all MVA were signifcantly higher in PGCL. Positive
      correlation between MVA-CD10S with FASNpositive mononuclear cells in both lesions
      was observed. CONCLUSIONS: Our results show both lesions exhibiting similar
      levels of FASN expression and neoangiogenesis, suggesting constitutive processes
      that regulate tissue maintenance.

PMID- 24676585
TI  - Evaluation of fluoride release from experimental TiF4 and NaF varnishes in vitro.
AB  - Fluoride varnishes play an important role in the prevention of dental caries,
      promoting the inhibition of demineralization and the increase of
      remineralization. OBJECTIVE: This study aimed to analyze the amount of fluoride
      released into water and artificial saliva from experimental TiF4 and NaF
      varnishes, with different concentrations, for 12 h. MATERIAL AND METHODS:
      Fluoride varnishes were applied on acrylic blocks and then immersed in 10 ml of
      deionized water and artificial saliva in polystyrene bottles. The acrylic blocks
      were divided in seven groups (n=10): 1.55% TiF4 varnish (0.95% F, pH 1.0); 3.10%
      TiF4 varnish (1.90% F, pH 1.0); 3.10% and 4% TiF4 varnish (2.45% F, pH 1.0);
      2.10% NaF varnish (0.95% F, pH 5.0); 4.20% NaF varnish (1.90% F, pH 5.0); 5.42%
      NaF varnish (2.45% F, pH 5.0) and control (no treatment, n=5). The fluoride
      release was analyzed after 1/2, 1, 3, 6, 9 and 12 h of exposure. The analysis was
      performed using an ion-specific electrode coupled to a potentiometer. Two-way
      ANOVA and Bonferroni's test were applied for the statistical analysis (p<0.05).
      RESULTS: TiF4 varnishes released larger amounts of fluoride than NaF varnishes
      during the first 1/2 h, regardless of their concentration; 4% TiF4 varnish
      released more fluoride than NaF varnishes for the first 6 h. The peak of fluoride
      release occurred at 3 h. There was a better dose-response relationship among the
      varnishes exposed to water than to artificial saliva. CONCLUSIONS: The 3.10% and
      4% TiF4 -based varnishes have greater ability to release fluoride into water and
      artificial saliva compared to NaF varnish; however, more studies must be
      conducted to elucidate the mechanism of action of TiF4 varnish on tooth surface.

PMID- 24676586
TI  - All trans-retinoic acid (ATRA) induces re-differentiation of early transformed
      breast epithelial cells.
AB  - Retinoids have been used as potential chemotherapeutic or chemopreventive agents
      because of their differentiative, anti-proliferative, pro-apoptotic and
      antioxidant properties. We investigated the effect of all trans-retinoic acid
      (ATRA) at different stages of the neoplastic transformation using an in vitro
      model of breast cancer progression. This model was previously developed by
      treating the MCF-10F human normal breast epithelial cells with high dose of
      estradiol and consists of four cell lines which show a progressive neoplastic
      transformation: MCF-10F, normal stage; trMCF, transformed MCF-10F; bsMCF,
      invasive stage; and caMCF, tumorigenic stage. In 3D cultures, MCF-10F cells form
      tubules resembling the structures in the normal mammary gland. After treatment
      with estradiol, these cells formed tubules and spherical masses which are
      indicative of transformation. Cells that only formed spherical masses in collagen
      were isolated (trMCF clone 11) and treated with ATRA. After treatment with 10 or
      1 uM ATRA, the trMCF clone 11 cells showed tubules in collagen; 10 and 43% of the
      structures were tubules in cells treated with 10 and 1 uM ATRA, respectively.
      Gene expression studies showed that 207 genes upregulated in transformed trMCF
      clone 11 cells were downregulated after 1 uM ATRA treatment to levels comparable
      to those found in the normal breast epithelial cells MCF-10F. Furthermore, 236
      genes that were downregulated in trMCF clone 11 were upregulated after 1 uM ATRA
      treatment to similar levels shown in normal epithelial cells. These 443 genes
      defined a signature of the ATRA re-programming effect. Our results showed that 1
      uM ATRA was able to re-differentiate transformed cells at early stages of the
      neoplastic process and antagonistically regulate breast cancer associated genes.
      The invasive and tumorigenic cells did not show any changes in morphology after
      ATRA treatment. These results suggest that ATRA could be used as a
      chemopreventive agent to inhibit the progression of premalignant lesions of the
      breast. 

PMID- 24676587
TI  - Triptolide-induced in vitro and in vivo cytotoxicity in human breast cancer stem
      cells and primary breast cancer cells.
AB  - We investigated the potential efficacy of the Chinese herbal extract triptolide
      for the treatment of human breast cancer by measuring the triptolide-induced
      cytotoxicity in cultures of human primary breast cancer cells (BCCs) and breast
      cancer stem cells (BCSCs) in vitro and in vivo. Human BCCs and BCSCs from
      invasive ductal carcinoma samples were cultured and treated with 0.1, 0.5 or 1.0
      uM triptolide. Cell death and apoptosis were measured after 24, 48 and 72 h of
      treatment. Mammospheres were found to be highly tumorigenic when implanted
      subcutaneously in nude BALB/c mice. Triptolide was cytotoxic against both human
      primary BCCs and BCSCs in vitro (P<0.05), but the cytotoxicity was stronger
      against the BCCs. In response to 1 uM triptolide for 72 h, the apoptotic rates
      were approximately 60% for BCCs and 30% for BCSCs. The BCSCs exhibited a high
      formation rate of tumors when implanted subcutaneously in nude BALB/c mice.
      Triptolide treatment in vivo significantly inhibited tumor growth compared with
      mock treatment. In conclusion, the cytotoxicity of triptolide against BCCs and
      BCSCs in vitro and in vivo suggests that this natural diterpenoid triepoxide
      compound may have clinical applications for the suppression of breast tumor
      growth.

PMID- 24676588
TI  - Biomechanical properties of superficial musculoaponeurotic system tissue with vs
      without reinforcement with poly-4-hydroxybutyric acid absorbable mesh.
AB  - IMPORTANCE It is unknown whether poly-4-hydroxybutyric acid (P4HB)-reinforced
      superficial musculoaponeurotic system tissue (SMAS) plication techniques will
      support SMAS imbrication and plication and potentially improve outcomes in
      rhytidectomy. OBJECTIVES To evaluate the biomechanical properties (tissue
      breaking strength, suture tearing force, and stress relaxation) of the SMAS with
      vs without reinforcement with P4HB absorbable mesh and to correlate these results
      with potential clinical applications. DESIGN, SETTING, AND SAMPLES In a cadaver
      study at an academic setting, 12 fresh frozen cadaver heads were used.
      Rhytidectomy incisions were made, and the SMAS was harvested and prepared for
      strength and stress testing using an Instron device. MAIN OUTCOMES AND MEASURES
      Tissue breaking strength and suture tearing force were analyzed. Stress
      relaxation test results were also assessed. The results of the SMAS samples alone
      were compared with those reinforced with P4HB absorbable mesh. RESULTS Overall,
      there were significant differences noted in tissue breaking strength and suture
      tearing force between the 2 groups. When the SMAS was reinforced with absorbable
      mesh, significant improvements were observed in tissue breaking strength (P <
      .001) and suture tearing force (P < .003). In addition, less variability was
      demonstrated in the maximum tensile load-bearing quality of the SMAS when the
      repair was reinforced with P4HB. CONCLUSIONS AND RELEVANCE Reinforcement with
      P4HB absorbable mesh improves tissue breaking strength and suture tearing force
      in cadaveric SMAS. It also reduces the variability in load vs displacement seen
      among samples tested. These data suggest that P4HB-reinforced SMAS imbrication
      would support higher loads and provide more consistent, long-lasting SMAS support
      among patients undergoing rhytidectomy. Further studies are needed to correlate
      these data with clinical outcomes in rhytidectomy.

PMID- 24676589
TI  - [Pain management in elderly patients].
AB  - Given the current demographic changes there are an increasing number of elderly
      and very elderly patients in outpatient and inpatient care. Elderly and very
      elderly patients often suffer from pain and musculoskeletal conditions are a
      common cause of pain in the elderly. An effective pain management should not be
      withheld from elderly patients with rheumatic diseases. Untreated pain in elderly
      patients leads to functional impairment and immobility. In addition, the quality
      of life of patients is negatively affected and can lead to a loss of autonomy
      and/or social withdrawal. The treatment of elderly and very elderly patients is
      particularly challenging. There are special features that need to be considered
      in the choice of treatment. Altered pain presentation, comorbidities,
      nonadherence, polypharmacy and side effects of pain medications require a
      critical risk-benefit assessment and ongoing treatment monitoring of this special
      group of patients. 

PMID- 24676590
TI  - [Safety of antirheumatic drug treatment in the elderly].
AB  - Mainly due to the general demographic changes and decreasing mortality in
      rheumatic diseases based on therapeutic progress, the proportion of older
      patients treated by rheumatologists is growing. Drug treatment in the elderly,
      however, harbors certain risks including age-specific pharmacokinetic features
      and high rates of multimorbidity and polypharmacy resulting in a risk of drug
      interactions and adherence problems. Nevertheless, older patients suffering from
      rheumatic diseases ought to be treated with the same intensity and same targets
      as the younger counterparts. Bearing all these facts in mind it is a balancing
      act for rheumatologists to find an optimal treatment for the individual elderly
      patient. Fear of risks should not lead to hesitant use of drugs leaving these
      patients alone with treatment deficits, as some studies have suggested. 

PMID- 24676591
TI  - [Interaction between bone, fat and insulin].

PMID- 24676592
TI  - [Operative joint-preserving therapy of gonarthrosis].
AB  - The guiding principle of operative joint-preserving therapy of gonarthrosis is
      the search for a safe, minimally invasive, efficient and ultimately reasonably
      priced therapeutic procedure to preserve or restore joint integrity. A
      comprehensive analysis and treatment of pathologies adjacent to and distant (axis
      deviations) from the joint are prerequisites for success of treatment. A
      comparison of results from the current literature with respect to the operative
      treatment of arthritis is limited due to the divergence of indications,
      terminologies used, techniques of the therapeutic procedure, inhomogeneity of
      patient collectives and the different follow-up and control schemes (scores).
      Conclusive, prospective, randomized double blind studies with large case numbers
      are associated with a high degree of organizational effort in planning, patient
      recruitment and execution and remain a rarity. Long-term prognosis depends on the
      stage of arthritis at the time of the arthroscopic intervention. Operative
      measures, such as correction osteotomy can be effective in the early stages. A
      short duration of symptoms, mechanical blocking and low-grade cartilage damage
      are factors which have a favorable prognosis. Cell-based cartilage repair
      techniques can reduce secondary degenerative alterations only in cases of local
      cartilage damage representing a prearthritic condition. Advantages of autologous
      chondrocyte transplantation compared to microfracturing have been found depending
      on the size of the defect and the follow-up time period. Furthermore,
      preservation and replacement of primary knee stabilizers, such as the anterior
      cruciate ligament and meniscus, have an important function for secondary
      prevention. A one-for-all therapy for joint-preserving operative treatment of
      gonarthrosis is lacking. 

PMID- 24676593
TI  - Complementary and Alternative Medicine for Posttraumatic Stress Disorder
      Symptoms: A Systematic Review.
AB  - OBJECTIVES: To (1) characterize complementary and alternative medicine studies
      for posttraumatic stress disorder symptoms, (2) evaluate the quality of these
      studies, and (3) systematically grade the scientific evidence for individual CAM
      modalities for posttraumatic stress disorder. DESIGN: Systematic review. Eight
      data sources were searched. Selection criteria included any study design
      assessing posttraumatic stress disorder outcomes and any complementary and
      alternative medicine intervention. The body of evidence for each modality was
      assessed with the Natural Standard evidence-based, validated grading rationale.
      RESULTS AND CONCLUSIONS: Thirty-three studies (n = 1329) were reviewed.
      Scientific evidence of benefit for posttraumatic stress disorder was strong for
      repetitive transcranial magnetic stimulation and good for acupuncture,
      hypnotherapy, meditation, and visualization. Evidence was unclear or conflicting
      for biofeedback, relaxation, Emotional Freedom and Thought Field therapies, yoga,
      and natural products. Considerations for clinical applications and future
      research recommendations are discussed.

PMID- 24676594
TI  - Liver biopsy histopathology for diagnosis of Johne's disease in sheep.
AB  - Sheep with Johne's disease develop epithelioid macrophage microgranulomas,
      specific to Mycobacterium avium subsp. paratuberculosis (Map) infection, in the
      terminal ileum, mesenteric lymph nodes, and organs distant to the alimentary
      tract such as the liver. The objectives of this study were to determine whether
      liver pathology was present in ewes affected by Map and whether liver cores
      provide adequate tissue for this potential diagnostic marker. One hundred and
      twenty-six adult, low body condition ewes were euthanized, necropsied, and
      underwent simulated liver biopsy. Ileal lesions typical of Map were found in 60
      ewes. Hepatic epithelioid microgranulomas were observed in all ewes with Type 3b
      (n = 40) and 82% (n = 11) with Type 3c ileal lesions. None were found in ewes
      unaffected by Map or with Type 1, 2, or 3a ileal lesions. Liver biopsy core
      samples provided adequate tissue for histopathology with a sensitivity and
      specificity of 96% (95% confidence interval [CI], 0.87-0.99) and 100% (95% CI,
      0.95-1), respectively for detection of types 3b and 3c ileal lesions. 

PMID- 24676596
TI  - A duplication of the mouth associated with a dysontogenic cyst: a case report and
      discussion of theories of origin.
AB  - IMPORTANCE Diprosopus is a medical condition that refers to full or partial
      craniofacial duplication. A particular subset of this condition, duplication of
      the mouth, is an exceedingly rare condition, with 7 reported cases in the medical
      literature. The embryogenesis and mechanism of disease are not well understood.
      The objective of this report was to describe a case of partial facial duplication
      with a discussion of the previous literature, leading to a proposed theory of
      embryogenesis for this rare anomaly. OBSERVATIONS We present a rare case of
      duplication of the mouth associated with an intraoral dysontogenic cyst, which
      presented with upper airway obstruction. The diagnostic and management strategies
      are discussed, as well as the histopathological features and theories of
      embryogenesis. CONCLUSIONS AND RELEVANCE On the basis of our findings, we propose
      the mechanism of origin for duplication of the mouth to be duplication of the
      first branchial arch. This case offers a deeper understanding of the mechanism of
      this disease than previously reported. Additional basic science and clinical
      research is needed to corroborate this theory. 

PMID- 24676597
TI  - Exogenous IL-10 induces corneal transplantation immune tolerance by a mechanism
      associated with the altered Th1/Th2 cytokine ratio and the increased expression
      of TGF-beta.
AB  - The aim of the present study was to examine the effect of exogenous IL-10
      transfected rat dendritic cells (DCs) in corneal allografts. Rat lymphocyte
      separation medium and a cytokine induction method was used to extract and culture
      precursor cells of rat bone marrow-derived dendritic cells. A corneal transplant
      model was established, with Sprague-Dawley (SD) rats as the recipients and Wistar
      rats as the donors. Flow cytometry (FCM) was used to detect the expression of
      CD83, which indicates a mature dendritic cell, and a specific cell surface
      stimulatory molecule CD86. Western blot analysis was used to detect interleukin
      (IL)-10 protein expression and RT-PCR was used to detect cytokine IL-10, IL-2 and
      TGF-beta mRNA expression in each group. Compared with the other groups, the
      survival time of corneal grafts in the IL-10-green fluorescent protein (GFP)-DC
      group was significantly prolonged and H&E staining demonstrated mild graft edema
      and inflammatory cell infiltration. There was a high expression of IL-10 and a
      low expression of the surface antigens, CD83 and CD86, with a lower proliferation
      of T lymphocytes in the IL-10-GFP-DC group. The expression of IL-10 and TGF-beta
      in the IL-10-GFP-DC group was higher than that in the other groups, while the
      expression of IL-2 was lower. The transfection of the IL-10 gene inhibited
      dendritic cell maturation. IL-10 gene-modified immature dendritic cells (imDC)
      were able to inhibit corneal allograft rejection and induce immune tolerance to
      prolong the survival time of the corneal graft. The Th1/Th2 deviation and the
      high expression of TGF-beta may lead to immune tolerance.

PMID- 24676595
TI  - Novel SNPs and INDEL polymorphisms in the 3'UTR of DGAT1 gene: in silico analyses
      and a possible association.
AB  - Diacylglycerol-O-acyltransferase (DGAT1) gene encodes the rate-limiting enzyme of
      triglyceride synthesis. A polymorphism in this gene, DGAT1 K232A, has been
      associated with milk production and composition in taurine breeds. However, this
      polymorphism is not a good tool for ascertaining the effects of this QTL in Bos
      indicus (Zebu), since the frequency of the DGAT1 232A allele is too low in these
      breeds. We sequenced the 3'-untranslated region of DGAT1 gene in a sample of
      bulls of the breeds Guzera (Bos indicus) and Holstein (Bos taurus) and, using in
      silico analysis, we searched for genetic variation, evolutionary conservation,
      regulatory elements, and possible substitution effects. Six single nucleotide
      (SNPs) and one insertion-deletion (INDEL) polymorphisms were found in the Guzera
      bulls. Additionally, we developed a preliminary association study, using this
      INDEL polymorphism as a genetic marker. A significant association was detected (P
      <= 0.05) between the INDEL (DGAT1 3'UTR INDEL) and the breeding values (BV) for
      protein, fat, and milk yields over a 305-day lactation period. The DGAT1 3' UTR
      INDEL genotype I/I (I, for insertion) was associated with lower BVs (-38.77 kg
      for milk, -1.86 kg for fat, and -1.48 kg for protein yields), when compared to
      the genotype I/D (D, for deletion). I/D genotype was lower D/D genotype (-34.98
      kg milk, -1.73 kg fat, and -1.09 kg protein yields). This study reports the first
      polymorphism of DGAT1 3'UTR in the Guzera breed, as well as its association with
      BV for milk protein, fat, and milk yields.

PMID- 24676598
TI  - A Pd-based regioselective strategy to indole-1,2-fused 8- and 9-membered rings:
      their evaluation as potential scaffolds for apoptosis in zebrafish.
AB  - A strategy based on Pd-mediated ring closure of 1,2-disubstituted indoles
      containing an unactivated olefin leading to indole-1,2-fused 8- and 9-membered
      rings has been developed for the identification of new and potential scaffolds
      for apoptosis. A large number of fused indole derivatives containing an
      endocyclic double bond were synthesized using this robust methodology. A
      representative compound showed promising apoptotic properties in zebrafish
      embryos. 

PMID- 24676600
TI  - Temporal trends in liver-directed therapy of patients with intrahepatic
      cholangiocarcinoma in the United States: a population-based analysis.
AB  - BACKGROUND AND OBJECTIVES: Data on outcomes after liver-directed therapy for
      intrahepatic cholangiocarcinoma (ICC) are limited due to the rarity of the
      disease. We sought to define overall utilization and temporal trends of liver
      directed therapy for ICC. METHODS: We identified 5,388 patients with ICC using
      the Surveillance Epidemiology and End Results (SEER) database between 1983 and
      2010. Patients were characterized based on the type of liver-directed therapy
      received: surgical resection, ablation therapy, and radiation therapy. RESULTS:
      The majority of patients did not undergo liver-directed therapy (n = 4,156,
      77.1%). Among those undergoing liver-directed therapy, surgical resection was
      most commonly performed (n = 672, 54.5%) and its utilization increased threefold
      over time (P = 0.001). The use of ablation therapy alone was used in 5.2% of
      patients and increased nearly sixfold over time (P = 0.39) whereas the use of
      radiation therapy alone decreased by nearly half (P < 0.001). Overall median
      survival was 10 months. Poor predictors of survival include tumor-based factors
      such as regional and distant disease, as well as poorly differentiated and large
      tumors (>5 cm). CONCLUSION: There was a moderate improvement in overall survival
      in patients with ICC between 1983 and 2010. The majority of patients with ICC are
      not undergoing liver-directed therapy. Among those who do undergo liver-directed
      therapy, the use of ablation therapy and surgery are increasing with nearly three
      in five patients undergoing resection.

PMID- 24676601
TI  - LAPTM4B polymorphism is associated with non-small cell lung cancer susceptibility
      and prognosis.
AB  - Lysosome-associated protein transmembrane-4beta (LAPTM4B) is a novel cancer
      related gene that is upregulated in many tumors, and which plays important roles
      in carcinogenesis. It has two alleles, LAPTM4B 1 and LAPTM4B 2. LAPTM4B 1
      contains only one copy of a 19-bp sequence in the first exon, whereas LAPTM4B 2
      contains two tight tandem segments. Previous studies have shown that LAPTM4B 2 is
      a risk factor for susceptibility and prognosis of many tumors. The present study
      investigated the relationship between LAPTM4B polymorphism and non-small cell
      lung cancer (NSCLC) susceptibility and prognosis. We identified LAPTM4B genotypes
      with polymerase chain reaction (PCR) in peripheral blood samples. In the adjusted
      multivariate logistic regression analysis, we found that LAPTM4B 1/2, LAPTM4B 2/2
      exhibited 1.48-fold [95% confidence interval (CI), 1.076-2.037] and 2.855-fold
      (95%CI, 1.722-4.734) increases in the risk of developing NSCLC compared with non
      LAPTM4B 2 carriers. Furthermore, our results showed that overall survival time
      and disease-free survival time of patients with LAPTM4B 2 were significantly
      shorter than in patients carrying LAPTM4B 1 (P=0.001 and P=0.001, respectively).
      In addition, multivariate Cox regression analysis revealed that LAPTM4B 2 was
      also an independent prognostic factor for NSCLC. These results suggest that
      LAPTM4B polymorphisms may be a prospective marker for evaluating the risk and
      prognosis of NSCLC.

PMID- 24676604
TI  - Effect of body shape on tragus-to-wall distance in the normal population.
AB  - Ankylosing spondylitis (AS) may result in a loss of spinal mobility. Therefore,
      evaluation of spinal mobility is an essential part of follow-up of patients with
      AS. The tragus-to-wall distance (TWD) is one of the four spinal mobility
      assessment parameters of the Bath Ankylosing Spondylitis Metrology Index, an
      index used in the follow-up of patients with AS. The aim of this study was to
      investigate the effect of body shape on TWD. In total, 465 subjects aged 18 to 65
      years with no disorders affecting the spine or any joint or disturbing the normal
      anatomical posture were included in this study. Their weight, height, hip and
      chest circumferences, anterior superior iliac crest-to-wall distance (ASIS-WD),
      and TWD were measured. Correlations between the parameters were calculated. TWD
      was positively correlated with weight (p < 0.001, r = 0.389), height (p < 0.001,
      r = 0.174), hip circumference (p < 0.001, r = 0.296), chest circumference (p <
      0.001, r = 0.291), and ASIS-WD (p < 0.001, r = 0.292). Weight gain or loss may
      lead to incorrect interpretations during the patient's follow-up. Comparative
      studies with unevenly distributed groups in terms of weight and height may also
      misdirect the TWD results. 

PMID- 24676605
TI  - Mean platelet volume: a novel diagnostic factor of systemic lupus erythematosus?

PMID- 24676606
TI  - Chronic kidney disease and the aging population.

PMID- 24676607
TI  - [Vesicoureteral reflux in children - there is still much controversy].

PMID- 24676608
TI  - [Drug-drug interaction].

PMID- 24676609
TI  - [Primary vesicoureteral reflux: conservative therapy or surgical intervention].
AB  - INTRODUCTION: The relationship between urinary tract infections and primary
      vesicoureteral reflux may lead to permanent renal damage. In the literature an
      increasing number of spontaneous cure of vesicoureteral reflux in children and
      the significant decrease in surgical therapy has been observed. OBJECTIVE: To
      study the evolution of primary vesicoureteral reflux associated with recurring
      urinary tract infections settings in patients of the Pediatric Nephrology
      department of our institution, evaluating cases in which cure was achieved
      through conservative therapy only and those in which surgical intervention was
      required. METHODS: We analyzed records and collected data refers to parameters:
      sex, age upon the diagnosis of primary urinary infection, age upon diagnosis of
      vesicoureteral reflux, number of urinary tract infections, vesicoureteral reflux
      grade; renal function, renal scaring, other malformation of urinary tract, and
      surgical or conservative intervention. Statistical analysis was descriptive and
      conducted with the SPSS program. RESULTS: Within the subgroup of patients with
      grade IV and V, 63.6% of the cases evolved to surgical intervention and 36.4% to
      conservative intervention. In those with grades I, II, and III, 38.5% evolved to
      surgical treatment against 61.5% for conservative approach. Among those with
      bilateral vesicoureteral reflux, 72.7% had to undergo surgical intervention. No
      relationship was observed between the vesicoureteral reflux grade and the
      presence of renal scaring. CONCLUSION: Patients with low grade vesicoureteral
      reflux and recurring urinary tract infections tend to experience spontaneous
      reflux resolution with good renal evolution in the long term in a way that
      surgical intervention becomes limited to high grade reflux or when followed by
      other clinical issues.

PMID- 24676610
TI  - [Autosomal dominant polycystic kidney disease in hemodialysis patients in
      Southern Brazil].
AB  - INTRODUCTION: Autosomal dominant polycystic kidney disease is the most common
      hereditary renal disease in humans. OBJECTIVE: To examine the prevalence,
      clinical and laboratory characteristics of patients with polycystic kidneys and
      relate disease manifestations by gender. METHODS: This was an observational and
      retrospective study. All the medical records of patients with polycystic kidneys
      who initiated hemodialysis between 1995 and 2012, in four centers that treat
      patients of the coverage area of the 15th regional health Parana (Brazil), were
      analyzed. RESULTS: The study included 48 patients with polycystic kidneys, the
      primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The
      average age of dialysis initiation was 50.7 years and the follow-up time on
      dialysis until transplantation (36.5 months) was lower among men. Hypertension
      was the most frequent diagnosis in 73% of patients, predominantly in women
      (51.4%). The liver cyst was the most frequent extrarenal manifestations in men
      (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of
      men. The class of antihypertensive drug used was that acts on the renin
      angiotensin system with higher frequency of use among women (53.3%). The post
      dialysis urea was significantly higher in men. CONCLUSION: The prevalence of the
      disease is low among hemodialysis patients in southern Brazil. The differences
      observed between genders, with the exception of the post-dialysis urea, were not
      significant. The findings are different from those reported in North America and
      Europe.

PMID- 24676611
TI  - [Identifying potential drug interactions in chronic kidney disease patients].
AB  - INTRODUCTION: Drug interactions (DIs) are common in clinical practice and are
      directly related to factors such as polypharmacy, aging, hepatic metabolism and
      decreased renal function. Individuals with chronic kidney disease (CKD) often
      require multiple classes of drugs being at important risk for the development of
      DIs. OBJECTIVE: Identify potential interactions among drugs prescribed to
      patients with CKD on conservative treatment, and factors associated with their
      occurrence. METHODS: Observational cross-sectional study, with analysis of 558
      prescriptions. Potential DIs were identified by the database MICROMEDEX(r),
      software that provides an internationally known pharmacopoeia. RESULTS: There was
      a predominance of males (54.7%), seniors (69.4%), stage 3 CKD (47.5%), overweight
      and obese patients (66.7%). The most prevalent comorbidities were hypertension
      (68.5%) and diabetes mellitus (31.9%). Potential DIs were detected in 74.9% of
      prescriptions. Among the 1364 DIs diagnosed, 5 (0.4%) were contraindicated and
      229 (16.8%) of greater severity, which need immediate intervention. Interactions
      of moderate and low severity were identified in 1049 (76.9%) and 81 (5.9%)
      prescriptions, respectively. The probability of one DI increased by 2.5 times for
      each additional drug (CI = 2.18 to 3.03). Obesity, hypertension, diabetes as well
      as advanced stage of CKD were risk factors strongly associated with DI
      occurrence. CONCLUSION: Drug associations in individuals with CKD were related to
      high prevalence of serious DIs, especially in the later stages of the disease.

PMID- 24676612
TI  - [Evaluation of intima-media thickness in patients with chronic kidney disease not
      on dialysis: a prospective study of 24 months].
AB  - INTRODUCTION: Increased carotid intima-media thickness (IMT) is considered a
      marker of early-onset atherosclerosis and it seems to predict cardiovascular
      events in general population. The prognostic value of IMT in patients with early
      stage chronic kidney disease (CKD) has not been clearly established. OBJECTIVE:
      We aimed to evaluate the association between IMT and cardiovascular (CV) events
      and mortality in CKD patients. METHODS: A cohort of CKD patients in stage 2-4 was
      evaluated the occurrence of CV events and death in a 24 months follow-up.
      Laboratory data, carotid ultrasound and coronary computed tomography were
      performed at baseline. RESULTS: A total of 117 patients (57 +/- 11 years-old, 61%
      male) were evaluated. Mean glomerular filtration rate (eGFR) was 36 +/- 17
      mL/min, 96% of patients had hypertension, 23% diabetes and 27% were obese.
      Coronary calcification was found in 48% of the patients, with higher prevalence
      among CKD stage 4 (p = 0.02). The median value of IMT was 0.6 mm (0.4-0.7 mm).
      When compared to patients with IMT <= 0.6 mm, those with IMT > 0.6 mm were older
      (p = 0.001), had higher prevalence of male (p = 0.001) and had lower eGFR (p =
      0.01). These patients also had higher prevalence of coronary calcification (p =
      0.001). During the follow-up, there were no differences in the occurrence of
      cardiovascular events and deaths between the two groups. CONCLUSION: IMT in early
      stage CKD patients was related to coronary calcification, but not with the
      occurrence of cardiovascular events or death.

PMID- 24676613
TI  - [Skin lesions in chronic renal dialysis].
AB  - OBJECTIVE: Cutaneous and mucosal disorders are the most common problems in
      patients on long-term hemodialysis. The dialysis prolongs the life expectancy,
      giving time of these changes to manifest. The aim of this study was to evaluate
      the prevalence of dermatologic problems among patients with chronic renal disease
      (CRD) undergoing hemodialysis. METHODS: One hundred forty-five patients with
      chronic renal disease undergoing hemodialysis were studied. All patients were
      thoroughly examined for skin changes, hair, nails and mucous membranes by a
      single examiner and laboratory tests were assessed. The data were stored in a
      database Microsoft Excel and analyzed using descriptive statistics. The
      continuous variables were compared using Student's t-test and categorical
      variables the chi-square test or Fisher's Exact test. RESULTS: The study included
      145 patients, mean age of 53.6 +/- 14.7 years, predominantly male (64.1%) and
      caucasian (90.0%). The average time of dialysis was 43.3 +/- 42.3 months. The
      main underlying diseases were: hypertension in 33.8%, diabetes mellitus in 29.6%
      and chronic glomerulonephritis in 13.1% of the patients. The main dermatologic
      manifestations observed were: xerosis in 109 (75.2%), ecchymosis in 87 (60.0%),
      pruritus in 78 (53.8%) and lentigo in 33 (22.8%) patients. CONCLUSION: Our study
      showed the presence of more than one alteration per patient. Cutaneous
      alterations are frequent in patients on dialysis. Further studies are needed to
      better characterization and management of these dermatosis.

PMID- 24676614
TI  - [Report of the Brazilian Chronic Dialysis Census 2012].
AB  - INTRODUCTION: National chronic dialysis data are fundamental for treatment
      planning. OBJECTIVE: To report data of the annual survey of the Brazilian Society
      of Nephrology about chronic kidney disease patients on dialysis in July 2012.
      METHODS: A survey based on data of dialysis units from the whole country. The
      data collection was performed by using a questionnaire filled out on-line by the
      dialysis units in Brazil. RESULTS: 255 (31.9%) of the dialysis units in the
      country answered the questionnaire. In July 2012, the total estimated number of
      patients on dialysis in the country was 97,586. The estimated prevalence and
      incidence rates of chronic kidney disease on maintenance dialysis were 503 and
      177 patients per million population, respectively. The estimated number of new
      patients starting dialysis in 2012 was 34,366. The annual gross mortality rate
      was 18.8%. For prevalent patients, 31.9% were aged 65 years or older, 91.6% were
      on hemodialysis and 8.4% on peritoneal dialysis, 30,447 (31.2%) were on a waiting
      list of renal transplant, 28.5% were diabetics, 36.6% had serum phosphorus > 5.5
      mg/dl and 34.4% hemoglobin < 11 g/dl. A venous catheter was the vascular access
      for 14.5% of the hemodialysis patients. CONCLUSION: The prevalence and incidence
      rates of chronic kidney disease patients on dialysis increased, while the
      mortality rate tended to decrease compared with 2011. The indicators of the
      quality of maintenance dialysis remained stable with a trend towards decrease in
      levels of anemia. The data highlight the importance of the census to guide
      chronic dialysis therapy.

PMID- 24676615
TI  - [Vasculopathy in the kidney allograft at time of transplantation delays recovery
      of graft function after deceased-donor kidney transplantation].
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of donor and
      recipient characteristics on duration of delayed graft function (DGF) and 1-year
      serum creatinine (SCr), as a surrogate endpoint for allograft survival. METHODS:
      We reviewed 120 first cadaver kidney transplants carried out consecutively at our
      center to examine the effect on 1-year SCr of the presence and duration of DGF.
      RESULTS: DGF rate was 68%, with a median duration of 12 days (range, 1-61). Forty
      four (38%) patients presented DGF lasting 12 or more days (prolonged DGF group).
      Mean donor age was 43 +/- 13 years, 37% had hypertension and in 59% the cause of
      brain death was cardiovascular accident. The mean cold ischemia time was 23 +/- 5
      hours. Twenty-seven (23%) donors were classified as expanded-criteria donors
      according to OPTN criteria. The mean recipient age was 51 +/- 15 years. The
      recipients median time in dialysis was 43 months (range, 1-269) and 25% of them
      had panel reactive antibodies > 0%. Patients with prolonged DGF presented higher
      1-year SCr in comparison with patients without DGF (1.7 vs. 1.3 mg/dL,
      respectively, p = 0.03). In multivariate logistic regression analysis, the only
      significant factor contributing to the occurrence of prolonged DGF was the
      presence of vascular lesions in the kidney allograft at time of transplantation
      (HR 3.6, 95% CI 1.2-10.2; p = 0.02). CONCLUSION: The presence of vasculopathy in
      the kidney allograft at time of transplantation was identified as an important
      factor independently associated with prolonged DGF. Prolonged DGF negatively
      impacts 1-year graft function.

PMID- 24676616
TI  - [Membranous glomerulonephritis: new insights in pathophysiology and therapeutic
      approach].
AB  - During the last decade, several major breakthroughs have led to the
      identification of human podocyte membrane antigens. Experimental involving
      antipodocyte antibodies in human membranous nephropathy (MN) have opened a new
      line of thinking about this disease, relating as an autoimmune kidney disease. In
      this setting, the M-type phospholipase A2 receptor (PLA2R) was identified as the
      first major antigen target in human primary MN. Studies have demonstrated anti
      PLA2R antibodies against PLA2R ranging from 70 to 89% in patients with MN, but
      not in those with secondary MN. It has been suggested that the serum level of
      anti-PLA2R could be used for the diagnosis of idiopathic MN and for the
      monitoring of response to treatment. However, the coexistence of autoantibodies
      suggests a complex pathogenic pathway that involves different podocyte targets.
      New experimental models are needed to elucidate the appearance time and the role
      of each anti-podocyte antibody in MN development and progression. 

PMID- 24676617
TI  - [Fast reading of the KDIGO 2012: guidelines for evaluation and management of
      chronic kidney disease in clinical practice].
AB  - The authors of this "fast reading" present the data they have considered as more
      relevant in the KDIGO 2012 as concerned to evaluation and management of chronic
      kidney disease. The text does not correspond to their opinion, it is a brief
      presentation of guidelines that could be useful in clinical practice. 

PMID- 24676618
TI  - [Physiology of fluid and solute transport across the peritoneal membrane].
AB  - In this review, phenomena involved in fluid and solute exchange through the
      peritoneal membrane, both in the physiologic and in the peritoneal dialysis
      settings, are explained. For that purpose, mathematical models developed for the
      study of molecule transport through the membrane, such as the "Pore Model" and
      the "Distributive Model" are used. Scientific accomplishments in the field are
      described and areas that require additional research are also cited. Knowledge
      about the physiologic mechanisms involved in this renal replacement therapy
      modality, concerning events directly related to the peritoneal membrane itself,
      is synthesized in this manuscript. 

PMID- 24676619
TI  - Inhibition of renal glucose reabsorption as a novel treatment for diabetes
      patients.
AB  - The importance of the kidney in glucose homeostasis has been recognized for many
      years. Recent observations indicating a greater role of renal glucose metabolism
      in various physiologic and pathologic conditions have rekindled the interest in
      renal glucose handling as a potential target for the treatment of diabetes. The
      enormous capacity of the proximal tubular cells to reabsorb the filtered glucose
      load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT
      2), became the focus of attention. Original studies conducted in experimental
      animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia
      after pancreatectomy decreased as a result of forced glycosuria. Subsequently,
      several compounds with more selective SGLT-2 inhibition properties ("second
      generation") were developed. Some agents made it into pre-clinical and clinical
      trials and a few have already been approved for commercial use in the treatment
      of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2
      inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day
      accompanied by a decline in fasting and postprandial glucose with average
      decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent
      drop in blood pressure also have been reported. In contrast, transient polyuria,
      thirst with dehydration and occasional hypotension have been described early in
      the treatment. In addition, a significant increase in the occurrence of uro
      genital infections, particularly in women has been documented with the use of
      SGLT-2 inhibitors. CONCLUSION: Although long-term cardiovascular, renal and
      bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in
      the proper patient provide a unique insulin-independent therapeutic option in the
      management of obese type 2 diabetes patients.

PMID- 24676620
TI  - Lipoprotein glomerulopathy: a case report of a rare disease in a Brazilian child.
AB  - Lipoprotein glomerulopathy (LPG) is a rare autosomal recessive glomerulopathy
      associated with the deposition of lipoprotein thrombi in the capillary lumina due
      to apoE gene mutations. Abnormal plasma lipoprotein profile and marked increase
      in serum apoliprotein E (apoE) are characteristic clinical data. The compromised
      patients can present nephrotic syndrome, hematuria, and progressive renal
      failure. Herein, the authors present the first described case of LPG in a
      Brazilian male patient, 11 years, who presented with a steroid-resistant
      nephrotic syndrome. Renal function was normal. Kidney biopsy showed markedly
      enlarged glomerulus, with dilated capillary loops and weak eosinophilic
      lipoprotein thrombi in the capillary lumina. Interstitium, tubules, arteries, and
      veins showed normal histologic aspect. Genotypic study for the apoE gene showed
      the presence of the alleles E3 and E4. The diagnosis of LPG was then performed.
      The patient received lipid-lowering treatment. After 2 years of follow-up, renal
      function is gradually decreasing, with persisting heavy proteinuria, despite a
      marked decrease in serum cholesterol and triglycerides levels. 

PMID- 24676621
TI  - The chronic kidney disease outcomes and practice patterns study Brazil (CKDopps
      Brazil): design, data and methodology.
AB  - INTRODUCTION: The chronic kidney disease outcomes and practice patterns study
      (CKDopps) is an international observational, prospective, cohort study involving
      patients with chronic kidney disease (CKD) stages 3-5 [estimated glomerular
      filtration rate (eGFR) < 60 ml/min/1.73 m2, with a major focus upon care during
      the advanced CKD period (eGFR < 30 ml/min/1.73 m2)]. During a 1-year enrollment
      period, each one of the 22 selected clinics will enroll up to 60 advanced CKD
      patients (eGFR < 30 ml/min/1.73 m2 and not dialysis-dependent) and 20 earlier
      stage CKD patients (eGFR between 30-59 ml/min/1.73 m2). EXCLUSION CRITERIA: age <
      18 years old, patients on chronic dialysis or prior kidney transplant. The study
      timeline include up to one year for enrollment of patients at each clinic
      starting in the end of 2013, followed by up to 2-3 years of patient follow-up
      with collection of detailed longitudinal patient-level data, annual clinic
      practice-level surveys, and patient surveys. Analyses will apply regression
      models to evaluate the contribution of patient-level and clinic practice-level
      factors to study outcomes, and utilize instrumental variable-type techniques when
      appropriate. CONCLUSION: Launching in 2013, CKDopps Brazil will study advanced
      CKD care in a random selection of nephrology clinics across Brazil to gain
      understanding of variation in care across the country, and as part of a
      multinational study to identify optimal treatment practices to slow kidney
      disease progression and improve outcomes during the transition period to end
      stage kidney disease.

PMID- 24676622
TI  - [Nephrology: is a medical specialty unattractive to Peruvian doctors?].
AB  - Although the National Committee of Medical Residency (CONAREME) has increased the
      number of nephrology residency positions in Peru, the increase has not been
      proportional to the number of applicants. This is worrisome in an environment
      lacking of nephrologists, like our country. The Peruvian Society of Nephrology
      (SPN) should take the measures to make this specialty more attractive to Peruvian
      physicians. 

PMID- 24676624
TI  - Impact of comorbidity on outcome of older breast cancer patients: a FOCUS cohort
      study.
AB  - Older breast cancer patients often suffer from comorbid diseases, which may
      influence life expectancy. The aim of this study was to assess the impact of
      specific comorbidities on overall survival and distant recurrence free period
      (DRFP) of older breast cancer patients. Patients were included from the
      population-based FOCUS cohort which contains 3,672 breast cancer patients aged 65
      years or older. The impact of comorbidity on overall survival and DRFP was
      analyzed using multivariable Cox proportional hazard models and Poisson
      regression models. Median follow-up time was 6.8 years (range 0-14.0).
      Irrespective of age; the number of comorbid diseases was significantly associated
      with worse overall survival [hazard ratio (HR) per increasing number of comorbid
      diseases: 1.20, 95 % confidence interval (CI) 1.13-1.27 and HR 1.09, 95 % CI 1.05
      1.13 for age <75 and age >= 75, respectively]. Median follow-up time for DRFP was
      5.7 years (range 0-14.0). An increasing number of comorbid diseases was
      associated with a decreasing risk of metastases among patients aged >= 75 (HR
      0.94, 95 % CI 0.87-1.02), whereas an increasing risk was shown for patients aged
      <75 (HR 1.09, 95 % CI 1.01-1.19). This study shows that in older breast cancer,
      patients overall survival and DRFP are influenced by comorbidity. This reiterates
      that patient outcome is not only influenced by breast cancer, and non-cancer
      related factors should be taken into account.

PMID- 24676623
TI  - Human papillomavirus and oropharyngeal cancer, the epidemics, and significance of
      additional clinical biomarkers for prediction of response to therapy (Review).
AB  - In 2007, the International Agency for Research against Cancer (IARC) recognized
      human papillomavirus (HPV), especially HPV16, besides smoking and alcohol, as a
      risk factor for oropharyngeal squamous cell carcinoma (OPSCC), where tonsillar
      and base of tongue cancer dominate. Moreover, during the past decade, in many
      Western countries, a sharp rise in the incidence of OPSCC, more specifically of
      HPV-positive OPSCC has been observed. Notably, patients with HPV-positive OPSCC,
      where the majority are men, particularly never-smokers have a better clinical
      outcome than patients with HPV-negative OPSCC and other head neck cancer (roughly
      80 vs. 40% disease-free survival with conventional radiotherapy and surgery).
      This suggests that many patients with HPV-positive OPSCC may not require the more
      aggressive intensified chemo-radiotherapy given to head neck cancer patients
      today, and could with somewhat tapered treatment maintain excellent survival,
      avoiding some of the severe side effects along with intensified treatment.
      However, before de-intensified treatment is administered additional biomarkers
      are necessary in combination with HPV-positive status in order to predict and
      select patients that will respond favorably to therapy. In conclusion, noteworthy
      issues within this field with an increasing cohort of patients with HPV-positive
      OPSCC are better-tailored therapy and prevention. Patients with HPV-positive
      OPSCC, with biomarkers for good response to therapy e.g., low MHC class I, or
      CD44 expression or high numbers of CD8+ tumor infiltrating lymphocytes, could be
      included in randomized trials with less severe therapy. Furthermore,
      possibilities to screen for HPV-positive OPSCC and to vaccinate boys against HPV
      infection should be further investigated. 

PMID- 24676625
TI  - Elderly primary care hypertension patients-who to refer for echocardiography?

PMID- 24676626
TI  - Conservative management for vocal fold polyps.
AB  - IMPORTANCE Classically, surgery has been the mainstay of management for vocal
      fold (VF) polyps. However, a significant portion of patients experience
      spontaneous regression and may not require surgery. OBJECTIVES To report the
      results of conservative management for VF polyps, identify patients with polyps
      that are more likely to resolve, and describe the time course of resolution.
      DESIGN, SETTING, AND PARTICIPANTS In this case series of 248 patients with VF
      polyps conducted presenting to a tertiary referral center, 94 patients were
      treated conservatively with at least 3 months of follow-up. All laryngoscopy
      photodocumentation and medical records were reviewed retrospectively.
      INTERVENTIONS Conservative management with close follow-up. MAIN OUTCOMES AND
      MEASURES Time course and resolution of VF polyps. RESULTS Of 94 VF polyps, 43
      (46%) showed a clinically significant reduction in size, and 36 (38%) resolved
      completely without requiring surgery. Multivariate analysis showed that VF polyps
      were most likely to resolve in female patients and in those with small-sized
      polyp and shorter symptom duration. Of the resolved polyps, 44% and 81% were
      resolved at 3 months and 8 months, respectively. CONCLUSIONS AND RELEVANCE
      Selected patients with VF polyp may benefit from conservative management,
      especially female patients and those with small, recent-onset polyps. The
      majority of polyps that resolve do so within 8 months, which can assist clinical
      decision making and counseling. 

PMID- 24676627
TI  - Landmine-detection rats: an evaluation of reinforcement procedures under
      simulated operational conditions.
AB  - Because the location of landmines is initially unknown, it is impossible to
      arrange differential reinforcement for accurate detection of landmines by pouched
      rats working on actual minefields. Therefore, provision must be made for
      maintenance of accurate responses by an alternative reinforcement strategy. The
      present experiment evaluated a procedure in which a plastic bag containing 2,4,6
      trinitrotoluene (TNT), the active ingredient in most landmines, was placed in
      contact with the ground in a disturbed area, then removed, to establish
      opportunities for reinforcement. Each of five rats continued to accurately detect
      landmines when extinction was arranged for landmine-detection responses and
      detections of TNT-contaminated locations were reinforced under a fixed-ratio 1
      schedule. The results of this translational research study suggest that the TNT
      contamination procedure is a viable option for arranging reinforcement
      opportunities for rats engaged in actual landmine-detection activities and the
      viability of this procedure is currently being evaluated on minefields in Angola
      and Mozambique. 

PMID- 24676628
TI  - Quality of care of rural rheumatoid arthritis patients in Austria.
AB  - OBJECTIVES: To determine how fast rheumatoid arthritis (RA) was diagnosed in a
      group of patients in a rural area and whether medical care and patient
      satisfaction were adequate in a predominantly non-urban settlement. METHODS: When
      visiting their rheumatologist, patients with RA were asked to complete a
      questionnaire at home after the consultation and then return it to an independent
      opinion research centre, where the data were collected and analysed. The form
      comprised various areas, namely demography, aspects of the diagnosis, medical
      care, therapeutic measures and the illness in a personal context. RESULTS: Of 150
      patients, 127 answered the questionnaire. A total of 63 % of the patients lived
      in settlements of less than 5,000 inhabitants, and a further 18 % in settlements
      of more than 5,000-50,000 inhabitants. The rheumatologist attended could be
      reached within 1 h for 90 % of the patients. In slightly fewer than 30 % of the
      respondents, the diagnosis of RA was made within 3 months, and in 44%, within 6
      months. In 75 %, the diagnosis was made by a rheumatologist. After experiencing
      the first symptoms, 80 % of the respondents contacted their general practitioner.
      A high degree of satisfaction appears to originate from the information supplied
      by the rheumatologist attended. Most patients believed they were involved in
      decision making regarding their therapy. CONCLUSION: The majority of the
      respondents came from rural areas. RA was diagnosed within 6 months for almost
      half of the patients questioned. Most patients believed they were well informed
      and involved in therapeutic decision making.

PMID- 24676630
TI  - Neutrophil-rich anaplastic large cell lymphoma expressing interleukin-8.

PMID- 24676629
TI  - Could selenium administration alleviate the disturbances of blood parameters
      caused by lithium administration in rats?
AB  - Lithium is widely used in medicine, but its administration can cause numerous
      side effects. The present study aimed at the evaluation of the possible
      application of selenium, an essential and antioxidant element, as a protective
      agent against lithium toxicity. The experiment was performed on four groups of
      Wistar rats: I (control)-treated with saline, II (Li)-treated with lithium
      (Li2CO3), III (Se)-treated with selenium (Na2SeO3) and IV (Li + Se)-treated with
      lithium and selenium (Li2CO3 and Na2SeO3) in the form of water solutions by
      stomach tube for 6 weeks. The following biochemical parameters were measured:
      concentrations of sodium, potassium, calcium, magnesium, phosphorus, iron, urea,
      creatinine, cholesterol, glucose, total protein and albumin and activities of
      alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in
      serum as well as whole blood superoxide dismutase and glutathione peroxidase.
      Morphological parameters such as red blood cells, haemoglobin, haematocrit, mean
      corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin
      concentration, platelets, white blood cells, neutrophils as well as lymphocytes
      were determined. Lithium significantly increased serum calcium and glucose (2.65
      +/- 0.17 vs. 2.43 +/- 0.11; 162 +/- 31 vs. 121 +/- 14, respectively), whereas
      magnesium and albumin were decreased (1.05 +/- 0.08 vs. 1.21 +/- 0.15; 3.85. +/-
      0.12 vs. 4.02 +/- 0.08, respectively). Selenium given with lithium restored these
      parameters to values similar to those observed in the control (Ca-2.49 +/- 0.08,
      glucose-113 +/- 26, Mg-1.28 +/- 0.09, albumin-4.07 +/- 0.11). Se alone or co
      administered with Li significantly increased aspartate aminotransferase and
      glutathione peroxidase. The obtained outcomes let us suggest that the
      continuation of research on the application of selenium as an adjuvant in lithium
      therapy seems warranted. 

PMID- 24676631
TI  - Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia
      in colitis-associated colorectal cancer acting on Notch signaling and gut
      microbiota.
AB  - Inflammatory bowel diseases are associated with increased risk of developing
      colitis-associated colorectal cancer (CAC). Epidemiological data show that the
      consumption of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) decreases the
      risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown
      that eicosapentaenoic acid-free fatty acid (EPA-FFA) reduces polyp formation and
      growth in models of familial adenomatous polyposis. However, the effects of
      dietary EPA-FFA are unknown in CAC. We tested the effectiveness of substituting
      EPA-FFA, for other dietary fats, in preventing inflammation and cancer in the AOM
      DSS model of CAC. The AOM-DSS protocols were designed to evaluate the effect of
      EPA-FFA on both initiation and promotion of carcinogenesis. We found that EPA-FFA
      diet strongly decreased tumor multiplicity, incidence and maximum tumor size in
      the promotion and initiation arms. Moreover EPA-FFA, in particular in the
      initiation arm, led to reduced cell proliferation and nuclear beta-catenin
      expression, whilst it increased apoptosis. In both arms, EPA-FFA treatment led to
      increased membrane switch from omega-6 to omega-3 PUFAs and a concomitant
      reduction in PGE2 production. We observed no significant changes in intestinal
      inflammation between EPA-FFA treated arms and AOM-DSS controls. Importantly, we
      found that EPA-FFA treatment restored the loss of Notch signaling found in the
      AOM-DSS control and resulted in the enrichment of Lactobacillus species in the
      gut microbiota. Taken together, our data suggest that EPA-FFA is an excellent
      candidate for CRC chemoprevention in CAC. 

PMID- 24676632
TI  - Evaluation of the shear bond strength of resin cement to Y-TZP ceramic after
      different surface treatments.
AB  - The purpose of this study was to evaluate the effect of various surface
      treatments on the shear bond strength of Y-TZP (Yttria-Tetragonal Zirconia
      Polycrystal) ceramics with zirconia primer and two different resin cements both
      containing 10-methacryloyloxydecyl dihydrogen phosphate (MDP). Zirconia blocks
      (LAVA, 3M ESPE, St. Paul, MN) were polished and assigned to five groups according
      to the surface treatment: (1) no further treatment (control); (2) airborne
      abrasion with Al2 O3 particles; (3) Z-PRIME Plus (Bisco, Schaumburg, IL) applied
      on polished zirconia; (4) Z-PRIME Plus applied on zirconia after airborne
      abrasion; and (5) tribochemical silica-coating performed with the CoJet system
      (3M ESPE) followed by application of ESPE(r)-Sil (3M ESPE). Each group was
      further divided into one of two resin cements: Panavia F2.0 (Kuraray, Kurashiki,
      Okayama, Japan) and Clearfil SA Luting (Kuraray). Resin cement placed inside a
      gel-cap was polymerized on the zirconia surface. Shear bond strength was tested
      with a universal testing machine at 0.5 mm/min. One-way analysis of variance and
      paired t-test were done. (p < 0.05), and scanning electron microscope (SEM)
      images were taken. Zirconia primer applied after airborne abrasion significantly
      increased the shear bond strength resulting in the highest value for both resin
      cements. Control groups for both cements showed the weakest value for shear bond
      strength. No significant differences were found between the shear bond strengths
      of the individual resin cements applied to zirconia surfaces treated the same
      way. In conclusion, the combined surface treatment of airborne abrasion followed
      by a zirconia primer is recommended for zirconia bonding with Panavia F2.0 and
      Clearfil SA Luting cements.

PMID- 24676633
TI  - Tell-tale signs of perturbed podocytes.

PMID- 24676634
TI  - Mutations in PAX2 associate with adult-onset FSGS.
AB  - FSGS is characterized by the presence of partial sclerosis of some but not all
      glomeruli. Studies of familial FSGS have been instrumental in identifying
      podocytes as critical elements in maintaining glomerular function, but underlying
      mutations have not been identified for all forms of this genetically
      heterogeneous condition. Here, exome sequencing in members of an index family
      with dominant FSGS revealed a nonconservative, disease-segregating variant in the
      PAX2 transcription factor gene. Sequencing in probands of a familial FSGS cohort
      revealed seven rare and private heterozygous single nucleotide substitutions (4%
      of individuals). Further sequencing revealed seven private missense variants (8%)
      in a cohort of individuals with congenital abnormalities of the kidney and
      urinary tract. As predicted by in silico structural modeling analyses, in vitro
      functional studies documented that several of the FSGS-associated PAX2 mutations
      perturb protein function by affecting proper binding to DNA and transactivation
      activity or by altering the interaction of PAX2 with repressor proteins,
      resulting in enhanced repressor activity. Thus, mutations in PAX2 may contribute
      to adult-onset FSGS in the absence of overt extrarenal manifestations. These
      results expand the phenotypic spectrum associated with PAX2 mutations, which have
      been shown to lead to congenital abnormalities of the kidney and urinary tract as
      part of papillorenal syndrome. Moreover, these results indicate PAX2 mutations
      can cause disease through haploinsufficiency and dominant negative effects, which
      could have implications for tailoring individualized drug therapy in the future. 

PMID- 24676637
TI  - ASN Presidential Address 2013: innovation and individualization--the path forward
      for nephrology.

PMID- 24676635
TI  - Tribbles homolog 3 attenuates mammalian target of rapamycin complex-2 signaling
      and inflammation in the diabetic kidney.
AB  - The endoplasmic reticulum (ER) stress response is activated in the diabetic
      kidney and functions to reduce ER protein accumulation and improve cellular
      function. We previously showed that tribbles homolog 3 (TRB3), an ER stress
      associated protein, is upregulated in the diabetic kidney. Here, we investigated
      whether absence of TRB3 alters outcomes in diabetic nephropathy. Type 1 diabetes
      was induced in TRB3 wild-type and knockout ((-/-)) mice by low-dose
      streptozotocin, and the mice were followed for 12 weeks. Diabetic TRB3(-/-) mice
      developed higher levels of albuminuria and increased expression of inflammatory
      cytokine and chemokine mRNA in renal cortices relative to wild-type littermates,
      despite similar hyperglycemia. Diabetic TRB3(-/-) mice also expressed higher
      levels of ER stress-associated molecules in both the renal cortices and
      glomeruli. This change was associated with higher renal cortical phosphorylation
      of AKT at serine 473 (Ser(473)), which is the AKT site phosphorylated by
      mammalian target of rapamycin complex-2 (mTORC2). We show in renal tubular cells
      that TRB3 binds to mTOR and the rapamycin-insensitive companion of mTOR (Rictor),
      a protein specific to mTORC2. Finally, we demonstrate in murine tubular cells
      that TRB3 can inhibit secretion of IL-6. Thus, TRB3 reduces albuminuria and
      inflammatory gene expression in diabetic kidney disease by a mechanism that may
      involve inhibition of the mTORC2/AKT pathway and may prove to be a novel
      therapeutic target. 

PMID- 24676636
TI  - Mutations in the gene that encodes the F-actin binding protein anillin cause
      FSGS.
AB  - FSGS is characterized by segmental scarring of the glomerulus and is a leading
      cause of kidney failure. Identification of genes causing FSGS has improved our
      understanding of disease mechanisms and points to defects in the glomerular
      epithelial cell, the podocyte, as a major factor in disease pathogenesis. Using a
      combination of genome-wide linkage studies and whole-exome sequencing in a
      kindred with familial FSGS, we identified a missense mutation R431C in anillin
      (ANLN), an F-actin binding cell cycle gene, as a cause of FSGS. We screened 250
      additional families with FSGS and found another variant, G618C, that segregates
      with disease in a second family with FSGS. We demonstrate upregulation of anillin
      in podocytes in kidney biopsy specimens from individuals with FSGS and kidney
      samples from a murine model of HIV-1-associated nephropathy. Overexpression of
      R431C mutant ANLN in immortalized human podocytes results in enhanced podocyte
      motility. The mutant anillin displays reduced binding to the slit diaphragm
      associated scaffold protein CD2AP. Knockdown of the ANLN gene in zebrafish
      morphants caused a loss of glomerular filtration barrier integrity, podocyte foot
      process effacement, and an edematous phenotype. Collectively, these findings
      suggest that anillin is important in maintaining the integrity of the podocyte
      actin cytoskeleton. 

PMID- 24676638
TI  - When erythropoietin meddles in immune affairs.

PMID- 24676639
TI  - Role of podocyte B7-1 in diabetic nephropathy.
AB  - Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy,
      but targeted therapies to halt or prevent these complications are currently not
      available. Here, we show that the immune-related molecule B7-1/CD80 is a critical
      mediator of podocyte injury in type 2 diabetic nephropathy. We report the
      induction of podocyte B7-1 in kidney biopsy specimens from patients with type 2
      diabetes. Genetic and epidemiologic studies revealed the association of two
      single nucleotide polymorphisms at the B7-1 gene with diabetic nephropathy.
      Furthermore, increased levels of the soluble isoform of the B7-1 ligand CD28
      correlated with the progression to ESRD in individuals with type 2 diabetes. In
      vitro, high glucose conditions prompted the phosphatidylinositol 3 kinase
      dependent upregulation of B7-1 in podocytes, and the ectopic expression of B7-1
      in podocytes increased apoptosis and induced disruption of the cytoskeleton that
      were reversed by the B7-1 inhibitor CTLA4-Ig. Podocyte expression of B7-1 was
      also induced in vivo in two murine models of diabetic nephropathy, and treatment
      with CTLA4-Ig prevented increased urinary albumin excretion and improved kidney
      pathology in these animals. Taken together, these results identify B7-1
      inhibition as a potential therapeutic strategy for the prevention or treatment of
      diabetic nephropathy.

PMID- 24676640
TI  - Urinary podocyte microparticles identify prealbuminuric diabetic glomerular
      injury.
AB  - Microparticles (MPs) are small (0.1-1.0 um) vesicles shed from the surface of
      cells in response to stress. Whether podocytes produce MPs and whether this
      production reflects glomerular injury are unclear. We examined MP formation in
      cultured human podocytes (hPODs) and diabetic mice. hPODs were exposed to
      cyclical stretch, high glucose (HG; 25 mM), angiotensin II, or TGF-beta. Urinary
      podocyte MPs were assessed in three mouse models of diabetic nephropathy:
      streptozotocin (STZ)-treated, OVE26, and Akita mice. Cyclic stretch and HG
      increased MP release as assessed by flow cytometry (P<0.01 and P<0.05,
      respectively, versus controls). Inhibition of Rho-kinase (ROCK) with fasudil
      blocked HG-induced podocyte MP formation. STZ-treated (8 weeks) mice exhibited
      increased urinary podocyte MPs compared with age-matched nondiabetic mice.
      Similarly, 16-week-old OVE26 mice had elevated levels of urinary podocyte MPs
      compared with wild-type littermates (P<0.01). In 1 week post-STZ-treated and 6-
      and 12-week-old Akita mice, urinary podocyte MPs increased significantly compared
      with those MPs in nondiabetic mice, despite normal urinary albumin levels. Our
      results indicate that podocytes produce MPs that are released into urine.
      Podocyte-derived MPs are generated by exposure to mechanical stretch and high
      glucose in vitro and could represent early markers of glomerular injury in
      diabetic nephropathy. 

PMID- 24676642
TI  - Distinguishing anemia and iron deficiency of heart failure: signal for severity
      of disease or unmet therapeutic need?
AB  - Despite advances in the management of heart failure (HF), quality of life and
      other outcomes remain suboptimal for many patients. Anemia and iron deficiency
      are comorbidities associated with adverse outcomes, although their
      pathophysiology in the setting of HF is not entirely understood. Anemia and iron
      deficiency may exist independently and may be a consequence of the systemic
      inflammatory state characterized by chronic HF. However, it is unclear whether
      serum hemoglobin concentrations and other hematologic parameters serve as markers
      for the severity of disease or represent novel therapeutic targets. Research in
      this area has focused primarily on therapies known to be effective for these
      conditions in other chronic disease states with similar pathophysiologic features
      (e.g., end-stage renal disease). Despite its many practical advantages, minimal
      evidence exists to support the use of oral iron supplementation in this setting.
      In contrast, intravenous iron has been the subject of several recent
      investigations, demonstrating improvements in both surrogate and clinical end
      points, although benefits seem to be the most substantial in patients with
      concomitant anemia. Erythropoietin-stimulating agents demonstrated early promise
      in retrospective analyses and small prospective trials, but their benefit was
      outweighed by a lack of improvement in clinical outcomes and an excess number of
      thromboembolic events in the largest trial of patients with anemia and HF to
      date. For acute symptomatic anemia, blood transfusion may be considered, although
      few trials have included patients with HF, and caution must be exerted in those
      who are hemodynamically unstable. Based on the currently available evidence,
      treatment of iron deficiency appears to confer benefit in patients with HF,
      whereas strategies aimed at improving hemoglobin alone do not. Included is a
      review of the pathophysiology of these conditions in the setting of HF, clinical
      trials evaluating pharmacologic therapy, and recommendations for management. 

PMID- 24676641
TI  - Immunosuppressive effects of erythropoietin on human alloreactive T cells.
AB  - Correction of anemia with erythropoietin (EPO) is associated with improved kidney
      transplant outcomes. Emerging evidence, predominantly from animal models,
      indicates that these observations may be erythropoiesis-independent and that EPO
      exhibits immunosuppressive properties. We examined the effects of EPO on human T
      cell alloimmunity by first documenting that CD4(+) and CD8(+) T cells express EPO
      receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a
      dose-dependent decrease in allogeneic CD4(+) T-cell proliferation (EPO 1000 U/ml:
      44.6%+/-22.9% of vehicle, P<0.05; 2000 U/ml: 11.1%+/-4% of vehicle, P<0.001)
      without inducing cell death. The effects required signals transmitted directly
      through the EPO-R expressed on T cells, resulting in diminished Th1
      differentiation without effects on regulatory T-cell induction. Mechanistic
      studies revealed that EPO prevented IL-2-induced proliferation by uncoupling IL-2
      receptor signaling, inhibiting phosphorylation of the intracellular
      intermediaries AKT and extracellular signal-regulated kinase that are known to
      mediate T-cell expansion. EPO treatment reduced expansion of human naive CD4(+) T
      cells after adoptive transfer into NOD scid gammac(null) mouse recipients,
      verifying the effects in vivo. Although activated T cells expressed CD131, an
      alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290,
      did not alter T-cell proliferation or cytokine production. Our findings link EPO
      R signaling on T cells to inhibition of T-cell immunity, providing one mechanism
      that could explain the observed protective effects of EPO in kidney transplant
      recipients. 

PMID- 24676643
TI  - Prescriber perceptions of a pediatric antimicrobial stewardship program.
AB  - Antimicrobial stewardship programs (ASPs) can help improve antimicrobial use in
      hospitals and, therefore, reduce resistance. Our hospital implemented an ASP in
      2004, with interventions based on Infectious Diseases Society of America
      recommendations. We aimed to assess the perceived effectiveness of ASP
      interventions on antimicrobial prescribing behavior by surveying hospital-based
      providers at a pediatric tertiary care center. We surveyed providers via an
      online survey utilizing questions with a Likert scale response format. Our ASP
      was perceived to be useful in improving antimicrobial use and was well received
      by prescribers. Hospitals considering creation of an ASP can anticipate that
      these interventions may affect prescribing behaviors in positive ways. 

PMID- 24676647
TI  - MicroRNA expression profiles in supraglottic carcinoma.
AB  - MicroRNAs (miRNAs) are single-stranded RNA molecules which regulate gene
      expression at the post-transcriptional level and several miRNAs have been found
      to be associated with some types of cancer. We sought to identify the expression
      and involvement of miRNAs in supraglottic carcinoma tissues compared with normal
      tissues and to determine whether miRNA expression is predictive of disease.
      Unsupervised clustering shows that miRNA profiles can distinguish tumor from
      normal tissues. Analysis of miRNA contents in supraglottic carcinoma highlighted
      nineteen differentially expressed miRNAs, three upregulated miRNAs (miR-21, miR
      19a, miR-33a) and two downregulated miRNAs (miR-206, miR-375). The microarray
      results of supraglottic carcinoma and related computer analysis may be beneficial
      for further analysis of cancer diagnosis and therapy.

PMID- 24676649
TI  - Vertebral body replacement with PEEK-cages after anterior corpectomy in
      multilevel cervical spinal stenosis: a clinical and radiological evaluation.
AB  - INTRODUCTION: A growing number of industrially manufactured implants have been
      developed in the last years for vertebral replacement in anterior cervical
      corpectomy and fusion (ACCF). Polyetheretherketone (PEEK)-cages are used in many
      centers, but outcome reports are scarce. This study assesses the clinical and
      radiological outcome after one- or two-level ACCF by the use of a PEEK-cage
      augmented by a plate-screw osteosynthesis. METHODS: A total of 21 patients
      received one-level (18 patients) or two-level (3 patients) ACCF by a PEEK-cage
      and plate-screw osteosynthesis for multilevel degenerative stenosis. The Visual
      Analogue Scale, Nurick Score, Neck Disability Index and European Myelopathy Score
      were used for clinical assessment. Radiological outcome-osseous fusion and loss
      of height-was evaluated by CT. RESULTS: The mean follow-up was 28 +/- 12 months.
      In 19 patients, bony fusion was achieved after the primary operation. Graft
      failure that required surgical revision occurred in two patients. In these
      patients, osseous fusion was achieved after the second operation. Myelopathy
      improved significantly. The loss of height was 2.2 +/- 2.3 and 5.3 +/- 2.1 mm
      after one- and two-level ACCF, respectively. CONCLUSION: Anterior corpectomy and
      fusion by a PEEK-cage and plate-screw osteosynthesis resulted in clinical
      improvement in all patients. Bony fusion was achieved in all patients in the long
      run. PEEK cages are allegedly less rigid than other xenografts. Similar to those,
      however, their use bears the risk of early cage-dislocation and subsidence. A
      comparison of industrial xenografts and autologous bone implants is required to
      challenge the different fusion techniques.

PMID- 24676648
TI  - A novel peptide to disrupt the interaction of BST-2 and Vpu.
AB  - Bone marrow stromal cell antigen 2 (BST-2) inhibits the release of HIV-1 and
      other enveloped viruses from the cell surface. HIV-1 Vpu binds to BST-2 through
      an interaction between transmembrane domains (TMD) of the two proteins and
      induces the downregulation of cell surface BST-2, thereby counteracting its
      antiviral activity. In this study, we designed and prepared a modified peptide
      BST2-TM-P1, which include the sequence of BST-2 TMD, keeping its property
      competing with BST-2 to bind with Vpu. Biological assay results indicate BST2-TM
      P1 could increase the BST-2 level at the cell surface in Vpu dependent manner and
      significantly inhibit the replication of HIV-1 virion. Our studies indicate that
      blocking the interaction of Vpu and BST-2 is an effective way to combat HIV-1
      infection.

PMID- 24676645
TI  - Myokines in insulin resistance and type 2 diabetes.
AB  - Skeletal muscle represents the largest organ of the body in non-obese individuals
      and is now considered to be an active endocrine organ releasing a host of so
      called myokines. These myokines are part of a complex network that mediates
      communication between muscle, the liver, adipose tissue, the brain and other
      organs. Recent data suggest that myokines regulated by muscle contraction may
      play a key role in mediating the health-promoting effects of regular physical
      activity. Although hundreds of myokines have recently been described in proteomic
      studies, we currently have a rather limited knowledge of the specific role these
      myokines play in the prevention of insulin resistance, inflammation and
      associated metabolic dysfunction. Several myokines are known to have both local
      and endocrine functions, but in many cases the contribution of physical activity
      to the systemic level of these molecules remains as yet unexplored. Very
      recently, novel myokines such as irisin, which is thought to induce a white to
      brown shift in adipocytes, have gained considerable interest as potential
      therapeutic targets. In this review, we summarise the most recent findings on the
      role of myokines in the regulation of substrate metabolism and insulin
      sensitivity. We further explore the role of myokines in the regulation of
      inflammation and provide a critical assessment of irisin and other myokines
      regarding their potential as therapeutic targets. 

PMID- 24676650
TI  - Lumbar spine stability after combined application of interspinous fastener and
      modified posterior lumbar interbody fusion: a biomechanical study.
AB  - INTRODUCTION: Posterior lumbar interbody fusion (PLIF) and internal fixation are
      commonly performed for the treatment of lower back pain due to lumbar spinal
      degeneration. We have developed a novel interspinous fixation device, the
      interspinous fastener (ISF) for potential use in the surgical management of
      degenerative spinal disease. The aim of this study was to assess the in vitro
      biomechanical characteristics of calf lumbar spine specimens after ISF fixation
      with modified PLIF. MATERIALS AND METHODS: Ten lumbar spine (L3-L6) specimens
      from ten fresh calf cadavers (8-10 weeks of age) were used. Each specimen
      underwent sequential testing for each of the following four groups: no
      instrumentation (INTACT); interspinous fusion device fixation + PLIF (ISF);
      unilateral pedicle screw and titanium rod fixation + PLIF (UPS); bilateral
      pedicle screw and titanium rod fixation + PLIF (BPS). Outcome measures included
      angular range of motion (ROM) during unloaded and loaded (8 Nm) flexion,
      extension, left bending, right bending, left torsion and right torsion. RESULTS:
      For all unloaded and loaded assessments, ROM was significantly higher in the
      INTACT group compared with all other groups (P < 0.05). Similarly, ROM was
      significantly higher in the UPS group (indicating decreased stability) compared
      with the ISF and BPS groups (P < 0.05). The only significant difference between
      the ISF and BPS groups was in the ROM with unloaded extension (higher in the BPS
      group, P = 0.006). CONCLUSIONS: We found that ISF fixation with PLIF of the lower
      lumbar spine provided biomechanical stability that was equivalent to that
      associated with bilateral pedicle screw/rod fixation with PLIF. The ISF shows
      potential as an alternative means of fixation in the surgical management of
      degenerative spinal disease.

PMID- 24676651
TI  - Treatment of postoperative pain after total hip arthroplasty: comparison between
      metamizol and paracetamol as adjunctive to opioid analgesics-prospective, double
      blind, randomised study.
AB  - INTRODUCTION: Metamizole use has been limited because of its risk of
      agranulocytosis. However, more recent literature seems to support its safety.
      This prospective, randomised, double-blind study was conducted to compare the
      analgesic effects of intravenous metamizole or intravenous paracetamol in
      combination with morphine PCA during the first 24 h following total hip
      arthroplasty. MATERIALS AND METHODS: One hundred ten consecutive patients were
      selected for study. The two study groups were (A) metamizole, (B) paracetamol.
      Postoperative pain therapy was provided by Morphine PCA pump. In the first
      treatment group (A group), all patients received intravenous metamizole 1.5 g
      every 8 h during the first 24 postoperative hours. In the second treatment group
      (B group), all patients received intravenous paracetamol 1 g every 8 h during the
      first 24 postoperative hours. Postoperative pain intensity was measured 1, 2, 3,
      4, 6, 8, 10, 14, 18, 22 h after the end of surgery by a VAS. RESULTS:
      Statistically significant differences in VAS pain values favoring metamizole were
      reported at 6-h (p = 0.038), 8-h (p = 0.036), 14-h (p = 0.011), 18-h (p < 0.001)
      and 22-h (p = 0.025) post-baseline. Mean cumulative pain values were 17.9 for
      metamizole and 30.6 for paracetamol. CONCLUSIONS: In this study, we have also
      shown excellent efficacy of paracetamol and metamizole combined with opioids, but
      metamizole proved to be a better analgesic than paracetamol. It is also necessary
      to mention the financial aspect considering that intravenous paracetamol is about
      ten times more expensive than an equivalent analgesic doses of intravenous
      metamizole.

PMID- 24676652
TI  - Anti-Mycobacterium tuberculosis activity and cytotoxicity of Calophyllum
      brasiliense Cambess (Clusiaceae).
AB  - We evaluated the in vitro anti-Mycobacterium tuberculosis activity and the
      cytotoxicity of dichloromethane extract and pure compounds from the leaves of
      Calophyllum brasiliense. Purification of the dichloromethane extract yielded the
      pure compounds (-) mammea A/BB (1), (-) mammea B/BB (2) and amentoflavone (3).
      The compound structures were elucidated on the basis of spectroscopic and
      spectrometric data. The contents of bioactive compounds in the extracts were
      quantified using high performance liquid chromatography coupled to an ultraviolet
      detector. The anti-M. tuberculosis activity of the extracts and the pure
      compounds was evaluated using a resazurin microtitre assay plate. The
      cytotoxicity assay was performed in J774G.8 macrophages using the 3-(4,5-dimethyl
      thiazol-2-yl)-2,5-diphenyl tetrazolium bromide colourimetric method. The
      quantification of the dichloromethane extract showed (1) and (2) at
      concentrations of 31.86 +/- 2.6 and 8.24 +/- 1.1 ug/mg of extract, respectively.
      The dichloromethane and aqueous extracts showed anti-M. tuberculosis H37Rv
      activity of 62.5 and 125 ug/mL, respectively. Coumarins (1) and (2) showed
      minimal inhibitory concentration ranges of 31.2 and 62.5 ug/mL against M.
      tuberculosis H37Rv and clinical isolates. Compound (3) showed no activity against
      M. tuberculosis H37Rv. The selectivity index ranged from 0.59-1.06. We report the
      activity of the extracts and coumarins from the leaves of C. brasiliense against
      M. tuberculosis. 

PMID- 24676653
TI  - Comparative analysis of the tissue inflammatory response in human cutaneous and
      disseminated leishmaniasis.
AB  - Cutaneous leishmaniasis (CL) is the most frequent clinical form of tegumentary
      leishmaniasis and is characterised by a single or a few ulcerated skin lesions
      that may disseminate into multiple ulcers and papules, which characterise
      disseminated leishmaniasis (DL). In this study, cells were quantified using
      immunohistochemistry and haematoxylin and eosin staining (CD4+, CD68+, CD20+,
      plasma cells and neutrophils) and histopathology was used to determine the level
      of inflammation in biopsies from patients with early CL, late CL and DL (ulcers
      and papules). The histopathology showed differences in the epidermis between the
      papules and ulcers from DL. An analysis of the cells present in the tissues
      showed similarities between the ulcers from localised CL (LCL) and DL. The
      papules had fewer CD4+ T cells than the DL ulcers. Although both CD4+ cells and
      macrophages contribute to inflammation in early CL, macrophages are the primary
      cell type associated with inflammation intensity in late ulcers. The higher
      frequency of CD20+ cells and plasma cells in lesions demonstrates the importance
      of B cells in the pathogenesis of leishmaniasis. The number of neutrophils was
      the same in all of the analysed groups. A comparison between the ulcers from LCL
      and DL and the early ulcers and papules shows that few differences between these
      two clinical forms can be distinguished by observing only the tissue. 

PMID- 24676654
TI  - Alterations in cytokines and haematological parameters during the acute and
      convalescent phases of Plasmodium falciparum and Plasmodium vivax infections.
AB  - Haematological and cytokine alterations in malaria are a broad and controversial
      subject in the literature. However, few studies have simultaneously evaluated
      various cytokines in a single patient group during the acute and convalescent
      phases of infection. The aim of this study was to sequentially characterise
      alterations in haematological patters and circulating plasma cytokine and
      chemokine levels in patients infected with Plasmodium vivax or Plasmodium
      falciparum from a Brazilian endemic area during the acute and convalescent phases
      of infection. During the acute phase, thrombocytopaenia, eosinopaenia,
      lymphopaenia and an increased number of band cells were observed in the majority
      of the patients. During the convalescent phase, the haematologic parameters
      returned to normal. During the acute phase, P. vivax and P. falciparum patients
      had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-gamma,
      tumour necrosis factor (TNF)-alpha, macrophage inflammatory protein-1beta and
      granulocyte-colony stimulating factor levels than controls and maintained high
      levels during the convalescent phase. IL-10 was detected at high concentrations
      during the acute phase, but returned to normal levels during the convalescent
      phase. Plasma IL-10 concentration was positively correlated with parasitaemia in
      P. vivax and P. falciparum-infected patients. The same was true for the TNF-alpha
      concentration in P. falciparum-infected patients. Finally, the haematological and
      cytokine profiles were similar between uncomplicated P. falciparum and P. vivax
      infections. 

PMID- 24676655
TI  - Intestinal parasites and genotyping of Giardia duodenalis in children: first
      report of genotype B in isolates from human clinical samples in Mexico.
AB  - Giardia duodenalis is one of the most prevalent enteroparasites in children. This
      parasite produces several clinical manifestations. The aim of this study was to
      determine the prevalence of genotypes of G. duodenalis causing infection in a
      region of southeastern Mexico. G. duodenalis cysts were isolated (33/429) from
      stool samples of children and molecular genotyping was performed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis,
      targeting the triosephosphate isomerase ( tpi ) and glutamate dehydrogenase ( gdh
      ) genes. The tpi gene was amplified in all of the cyst samples, either for
      assemblage A (27 samples) or assemblage B (6 samples). RFLP analysis classified
      the 27 tpi -A amplicons in assemblage A, subgenotype I. Samples classified as
      assemblage B were further analysed using PCR-RFLP of the gdh gene and identified
      as assemblage B, subgenotype III. To our knowledge, this is the first report of
      assemblage B of G. duodenalis in human clinical samples from Mexico. 

PMID- 24676656
TI  - Genotypes of pathogenic Leptospira spp isolated from rodents in Argentina.
AB  - Leptospirosis is the most widespread zoonosis in the world and significant
      efforts have been made to determine and classify pathogenic Leptospira strains.
      This zoonosis is maintained in nature through chronic renal infections of carrier
      animals, with rodents and other small mammals serving as the most important
      reservoirs. Additionally, domestic animals, such as livestock and dogs, are
      significant sources of human infection. In this study, a multiple-locus variable
      number tandem repeat analysis (MLVA) was applied to genotype 22 pathogenic
      Leptospira strains isolated from urban and periurban rodent populations from
      different regions of Argentina. Three MLVA profiles were identified in strains
      belonging to the species Leptospira interrogans (serovars Icterohaemorrhagiae and
      Canicola); one profile was observed in serovar Icterohaemorrhagiae and two MLVA
      profiles were observed in isolates of serovars Canicola and Portlandvere. All
      strains belonging to Leptospira borgpetersenii serovar Castellonis exhibited the
      same MLVA profile. Four different genotypes were isolated from urban populations
      of rodents, including both mice and rats and two different genotypes were
      isolated from periurban populations. 

PMID- 24676657
TI  - Parasite load and risk factors for poor outcome among children with visceral
      leishmaniasis. A cohort study in Belo Horizonte, Brazil, 2010-2011.
AB  - Clinical and laboratory risk factors for death from visceral leishmaniasis (VL)
      are relatively known, but quantitative real-time polymerase chain reaction (qPCR)
      might assess the role of parasite load in determining clinical outcome. The aim
      of this study was to identify risk factors, including parasite load in peripheral
      blood, for VL poor outcome among children. This prospective cohort study
      evaluated children aged <= 12 years old with VL diagnosis at three times: pre
      treatment (T0), during treatment (T1) and post-treatment (T2). Forty-eight
      patients were included and 16 (33.3%) met the criteria for poor outcome. Age <=
      12 months [relative risk (RR) 3.51; 95% confidence interval (CI) 1.89-6.52],
      tachydyspnoea (RR 3.46; 95% CI 2.19-5.47), bacterial infection (RR 3.08; 95% CI
      1.27-7.48), liver enlargement (RR 3.00; 95% CI 1.44-6.23) and low serum albumin
      (RR 7.00; 95% CI 1.80-27.24) were identified as risk factors. qPCR was positive
      in all patients at T0 and the parasite DNA was undetectable in 76.1% of them at
      T1 and in 90.7% at T2. There was no statistical association between parasite load
      at T0 and poor outcome.

PMID- 24676658
TI  - Genotyping Mycobacterium bovis from cattle in the Central Pampas of Argentina:
      temporal and regional trends.
AB  - Mycobacterium bovis is the causative agent of bovine tuberculosis (TB), a disease
      that affects approximately 5% of Argentinean cattle. Among the molecular methods
      for genotyping, the most convenient are spoligotyping and variable number of
      tandem repeats (VNTR). A total of 378 samples from bovines with visible lesions
      consistent with TB were collected at slaughterhouses in three provinces, yielding
      265 M. bovis spoligotyped isolates, which were distributed into 35 spoligotypes.
      In addition, 197 isolates were also typed by the VNTR method and 54 combined VNTR
      types were detected. There were 24 clusters and 27 orphan types. When both typing
      methods were combined, 98 spoligotypes and VNTR types were observed with 27
      clusters and 71 orphan types. By performing a meta-analysis with previous
      spoligotyping results, we identified regional and temporal trends in the
      population structure of M. bovis. For SB0140, the most predominant spoligotype in
      Argentina, the prevalence percentage remained high during different periods,
      varying from 25.5-57.8% (1994-2011). By contrast, the second and third most
      prevalent spoligotypes exhibited important fluctuations. This study shows that
      there has been an expansion in ancestral lineages as demonstrated by
      spoligotyping. However, exact tandem repeat typing suggests dynamic changes in
      the clonal population of this microorganism. 

PMID- 24676659
TI  - Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal,
      cytotoxic and genotoxic activities and their in vitro and in silico interactions
      with the Trypanosoma brucei nitroreductase enzyme.
AB  - Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi
      and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis.
      Compound 7 is not used clinically due to its mutagenic and genotoxic properties,
      but has been largely used as a lead compound. Here, we compared the activity of 7
      with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and
      T. cruzi and evaluated their activation by T. brucei type I nitroreductase
      (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these
      compounds in whole human blood using Comet and fluorescein diacetate/ethidium
      bromide assays. Although the only difference between 7 and 8 is the substitution
      of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the
      results indicated that 8 had poorer antiparasitic activity than 7 and was not
      genotoxic, whereas 7 presented this effect. The determination of Vmax indicated
      that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with
      better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and
      8 performed within the active site of a homology model of the TbNTR indicating
      that 8 had greater affinity than 7. 

PMID- 24676660
TI  - Acute Chagas disease in El Salvador 2000-2012 - need for surveillance and
      control.
AB  - Several parasitological studies carried out in El Salvador between 2000-2012
      showed a higher frequency of acute cases of Chagas disease than that in other
      Central American countries. There is an urgent need for improved Chagas disease
      surveillance and vector control programs in the provinces where acute Chagas
      disease occurs and throughout El Salvador as a whole. 

PMID- 24676661
TI  - High occurrence of Calodium hepaticum (syn. Capillaria hepatica) spurious
      infection in a village in the Atlantic Forest of southern Brazil.
AB  - Calodium hepaticum (syn. Capillaria hepatica) is a nematode of the Capillariidae
      family that infects rodents and other mammals. In Brazil, human spurious
      infections of C. hepaticum have been detected in indigenous or rural communities
      from the Amazon Basin, but not in the southern states of the country. Here, we
      report the highest occurrence (13.5% of 37 residents) of C. hepaticum human
      spurious infection detected in Brazil and the first record in a southern region,
      Guaraquecaba. The finding is explained by the area being located in the Atlantic
      Forest of the state of Parana, surrounded by preserved forests and because the
      inhabitants consume the meat of wild mammals. 

PMID- 24676662
TI  - Genetic diversity and antimicrobial resistance in Streptococcus agalactiae
      strains recovered from female carriers in the Bucharest area.
AB  - For the first time, we used multilocus sequence typing (MLST) to understand how
      Romanian group B streptococcus (GBS) strains fit into the global GBS population
      structure. Colonising isolates recovered from adult human females were tested for
      antibiotic resistance, were molecularly serotyped based on the capsular
      polysaccharide synthesis (cps) gene cluster and further characterised using a set
      of molecular markers (surface protein genes, pilus-encoded islands and mobile
      genetic elements inserted in the scpB-lmb intergenic region). Pulsed-field gel
      electrophoresis was used to complement the MLST clonal distribution pattern of
      selected strains. Among the 55 strains assigned to six cps types (Ia, Ib, II-V),
      18 sequence types (STs) were identified by MLST. Five STs represented new entries
      to the MLST database. The prevalent STs were ST-1, ST-17, ST-19 and ST-28. Twenty
      molecular marker profiles were identified. The most common profiles (rib+GBSi1+PI
      1, rib+GBSi1+PI-1, PI-2b and alp2/3+PI-1, PI-2a) were associated with the cps
      III/ST-17 and cps V/ST-1 strains. A cluster of fluoroquinolone-resistant strains
      was detected among the cps V/ST-19 members; these strains shared alp1 and IS1548
      and carried PI-1, PI-2a or both. Our results support the usefulness of
      implementing an integrated genotyping system at the reference laboratory level to
      obtain the reliable data required to make comparisons between countries. 

PMID- 24676663
TI  - Examining ERBB2 as a candidate gene for susceptibility to leprosy (Hansen's
      disease) in Brazil.
AB  - Leprosy remains prevalent in Brazil. ErbB2 is a receptor for leprosy bacilli
      entering Schwann cells, which mediates Mycobacterium leprae-induced demyelination
      and the ERBB2 gene lies within a leprosy susceptibility locus on chromosome 17q11
      q21. To determine whether polymorphisms at the ERBB2 locus contribute to this
      linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-SNPs)
      (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372
      individuals) from the state of Para (PA). All three tag-SNPs were associated with
      leprosy per se [best SNP rs2517959 odds ratio (OR) = 2.22; 95% confidence
      interval (CI) 1.37-3.59; p = 0.001]. Lepromatous (LL) (OR = 3.25; 95% CI 1.37
      7.70; p = 0.007) and tuberculoid (TT) (OR = 1.79; 95% CI 1.04-3.05; p = 0.034)
      leprosy both contributed to the association, which is consistent with the
      previous linkage to chromosome 17q11-q21 in the population from PA and supports
      the functional role of ErbB2 in disease pathogenesis. To attempt to replicate
      these findings, six SNPs (rs2517955, rs2517956, rs1810132, rs2952156, rs1801200,
      rs1058808) were genotyped in a population-based sample of 570 leprosy cases and
      370 controls from the state of Rio Grande do Norte (RN) and the results were
      analysed using logistic regression analysis. However, none of the associations
      were replicated in the RN sample, whether analysed for leprosy per se, LL
      leprosy, TT leprosy, erythema nodosum leprosum or reversal reaction conditions.
      The role of polymorphisms at ERBB2 in controlling susceptibility to leprosy in
      Brazil therefore remains unclear. 

PMID- 24676664
TI  - Low transformation growth factor-beta1 production and collagen synthesis
      correlate with the lack of hepatic periportal fibrosis development in
      undernourished mice infected with Schistosoma mansoni.
AB  - Undernourished mice infected (UI) submitted to low and long-lasting infections by
      Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is
      equivalent to Symmers' fibrosis in humans. In this report, the effects of the
      host's nutritional status on parasite (worm load, egg viability and maturation)
      and host (growth curves, biology, collagen synthesis and characteristics of the
      immunological response) were studied and these are considered as interdependent
      factors influencing the amount and distribution of fibrous tissue in hepatic
      periovular granulomas and portal spaces. The nutritional status of the host
      influenced the low body weight and low parasite burden detected in UI mice as
      well as the number, viability and maturation of released eggs. The reduced
      oviposition and increased number of degenerated or dead eggs were associated with
      low protein synthesis detected in deficient hosts, which likely induced the
      observed decrease in transformation growth factor (TGF)-beta1 and liver collagen.
      Despite the reduced number of mature eggs in UI mice, the activation of TGF-beta1
      and hepatic stellate cells occurred regardless of the unviability of most
      miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins.
      However, changes in the repair mechanisms influenced by the nutritional status in
      deficient animals may account for the decreased liver collagen detected in the
      present study. 

PMID- 24676665
TI  - Metallothionein-1 and nitric oxide expression are inversely correlated in a
      murine model of Chagas disease.
AB  - Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin
      America countries. The participation of free radicals, especially nitric oxide
      (NO), has been demonstrated in the pathophysiology of seropositive individuals
      with T. cruzi. In Chagas disease, increased NO contributes to the development of
      cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals
      scavengers of NO in vitro and in vivo. Here, we developed a murine model of the
      chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice,
      which were divided into four groups: infected non-treated (Inf), infected N
      monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non
      infected vehicle-treated. We determined blood parasitaemia and NO levels, the
      extent of parasite nests in tissues and liver MT-I expression levels. It was
      observed that NO levels were increasing in Inf mice in a time-dependent manner.
      Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with
      decreased blood NO levels at day 135 post infection. This affect was negatively
      correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In
      conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism
      reduces MT-I expression, allowing augmented NO levels. 

PMID- 24676666
TI  - Genetic characterisation of Langerin gene in human immunodeficiency virus-1
      infected women from Bahia, Brazil.
AB  - Studies on human genetic variations are a useful source of knowledge about human
      immunodeficiency virus (HIV)-1 infection. The Langerin protein, found at the
      surface of Langerhans cells, has an important protective role in HIV-1 infection.
      Differences in Langerin function due to host genetic factors could influence
      susceptibility to HIV-1 infection. To verify the frequency of mutations in the
      Langerin gene, 118 samples from HIV-1-infected women and 99 samples from HIV-1
      uninfected individuals were selected for sequencing of the promoter and
      carbohydrate recognition domain (CRD)-encoding regions of the Langerin gene.
      Langerin promoter analysis revealed two single nucleotide polymorphisms (SNPs)
      and one mutation in both studied groups, which created new binding sites for
      certain transcription factors, such as NFAT5, HOXB9.01 and STAT6.01, according to
      MatInspector software analysis. Three SNPs were observed in the CRD-encoding
      region in HIV-1-infected and uninfected individuals: p.K313I, c.941C>T and
      c.983C>T. This study shows that mutations in the Langerin gene are present in the
      analysed populations at different genotypic and allelic frequencies. Further
      studies should be conducted to verify the role of these mutations in HIV-1
      susceptibility. 

PMID- 24676667
TI  - A new rapid colourimetric method for testing Mycobacterium tuberculosis
      susceptibility to isoniazid and rifampicin: a crystal violet decolourisation
      assay.
AB  - The aim of this study was to investigate the performance of a new and accurate
      method for the detection of isoniazid (INH) and rifampicin (RIF) resistance among
      Mycobacterium tuberculosis isolates using a crystal violet decolourisation assay
      (CVDA). Fifty-five M. tuberculosis isolates obtained from culture stocks stored
      at -80oC were tested. After bacterial inoculation, the samples were incubated at
      37oC for seven days and 100 uL of CV (25 mg/L stock solution) was then added to
      the control and sample tubes. The tubes were incubated for an additional 24-48 h.
      CV (blue/purple) was decolourised in the presence of bacterial growth; thus, if
      CV lost its colour in a sample containing a drug, the tested isolate was reported
      as resistant. The sensitivity, specificity, positive predictive value, negative
      predictive value and agreement for INH were 92.5%, 96.4%, 96.1%, 93.1% and 94.5%,
      respectively, and 88.8%, 100%, 100%, 94.8% and 96.3%, respectively, for RIF. The
      results were obtained within eight-nine days. This study shows that CVDA is an
      effective method to detect M. tuberculosis resistance to INH and RIF in
      developing countries. This method is rapid, simple and inexpensive. Nonetheless,
      further studies are necessary before routine laboratory implementation. 

PMID- 24676668
TI  - Influence of iterative image reconstruction on CT-based calcium score
      measurements.
AB  - Iterative reconstruction techniques for coronary CT angiography have been
      introduced as an alternative for traditional filter back projection (FBP) to
      reduce image noise, allowing improved image quality and a potential for dose
      reduction. However, the impact of iterative reconstruction on the coronary artery
      calcium score is not fully known. In 112 consecutive stable patients with
      suspected coronary artery disease, the coronary calcium scores were assessed.
      Comparisons were made between the Agatston, volume and mass scores obtained with
      traditional FBP, and by using adaptive statistical iterative reconstruction
      (ASIR). A significant reduction of the Agatston score, volume score and mass
      score was observed for ASIR when compared to FBP, with median differences of
      resp. 26, 5 mm(3) and 1 mg. Using the ASIR reconstruction, the number of patients
      with a calcium score of zero increased by 13 %. Iterative CT reconstruction
      significantly reduces the Agatston, volume and mass scores. Since the calcium
      score is used as a prognostic tool for coronary artery disease, caution must be
      taken when using iterative reconstruction.

PMID- 24676669
TI  - Preference pulses without reinforcers.
AB  - Preference pulses are thought to represent strong, short-term effects of
      reinforcers on preference in concurrent schedules. However, the general shape of
      preference pulses is substantially determined by the distributions of responses
      per-visit (visit lengths) for the two choice alternatives. In several series of
      simulations, we varied the means and standard deviations of distributions
      describing visits to two concurrently available response alternatives, arranged
      "reinforcers" according to concurrent variable-interval schedules, and found a
      range of different preference pulses. Because characteristics of these
      distributions describe global aspects of behavior, and the simulations assumed no
      local effects of reinforcement, these preference pulses derive from the visit
      structure alone. This strongly questions whether preference pulses should
      continue to be interpreted as representing local effects of reinforcement. We
      suggest an alternative approach whereby local effects are assessed by subtracting
      the artifactual part, which derives from visit structure, from the observed
      preference pulses. This yields "residual" preference pulses. We illustrate this
      method in application to published data from mixed dependent concurrent
      schedules, revealing evidence that the delivery of reinforcers had modest
      lengthening effects on the duration of the current visit, a conclusion that is
      quantitatively consistent with early research on short-term effects of
      reinforcement. 

PMID- 24676670
TI  - Astragaloside IV reduces the expression level of P-glycoprotein in multidrug
      resistant human hepatic cancer cell lines.
AB  - Astragaloside is a saponin widely used in traditional Chinese medicine and has
      been reported to be a potent multidrug resistance (MDR) reversal agent. The
      present study investigated the role of astragaloside IV (ASIV) in the regulation
      of P-glycoprotein (P-gp, encoded by the mdr1 gene) and its effect on the reversal
      of MDR. The activity of ASIV was evaluated using human hepatic cancer cells Bel
      7402 and the corresponding 5-fluorouracil (5-FU) resistant cells Bel-7402/FU.
      ASIV (0.08 mg/ml) potentiated the cytotoxicity of 5-FU which was demonstrated
      using the MTT assay on Bel-7402/FU cells. ASIV reduced the expression of P-gp as
      was revealed by immunocytochemistry. Accumulation and efflux studies with the P
      gp substrate, rhodamine 123 (Rh123), demonstrated that ASIV inhibited P-gp
      mediated drug efflux. Furthermore, it was demonstrated that ASIV enhanced the
      drug accumulation of 5-FU using a high performance liquid chromatography (HPLC)
      assay for drug resistant cells. Furthermore, ASIV may downregulate the expression
      of P-gp, which was examined using western blot analysis and polymerase chain
      reaction. In conclusion, the results of the present study indicated that ASIV
      reverses the drug resistance of Bel-7402/FU cells by downregulating the
      expression of mdr1. ASIV may represent a potent modulator of P-gp-mediated MDR in
      hepatic cancer therapy.

PMID- 24676672
TI  - Marked referential communicative behaviours, but no differentiation of the
      "knowledge state" of humans in untrained pet dogs versus 1-year-old infants.
AB  - The study examines whether untrained dogs and infants take their caregiver's
      visual experience into account when communicating with them. Fifteen adult dogs
      and 15 one-year-old infants were brought into play with their caregivers with one
      of their own toys. The caregiver gave the toy to the experimenter, who, in
      different conditions, placed it either above or under one of two containers, with
      both the infant or dog and the caregiver witnessing the positioning; in a third
      condition, the caregiver left the room before the toy was placed under one of the
      two containers and later returned. Afterwards, for each condition, the caregiver
      asked the participant to indicate the location of the toy. Neither dogs nor
      infants-untrained to the use of the partner's knowledge state-showed much
      difference of behaviour between the three conditions. However, dogs showed more
      persistence for most behaviours (gaze at the owner, gaze at the toy and gaze
      alternation) and conditions, suggesting that the situation made more demands on
      dogs' communicative behaviours than on those of infants. When all deictic
      behaviours of infants (arm points towards the toy and gaze at the toy) were taken
      into account, dogs and infants did not differ. Phylogeny, early experience and
      ontogeny may all play a role in the ways that both species communicate with adult
      humans. 

PMID- 24676671
TI  - The secretion of IL-6 by CpG-ODN-treated cancer cells promotes T-cell immune
      responses partly through the TLR-9/AP-1 pathway in oral squamous cell carcinoma.
AB  - Increasing evidence suggests that communication between tumor and immune cells
      can alter the tumor microenvironment in ways that promote tumor development. The
      purpose of this study was to characterize the immune response elicited by TLR-9
      activated OSCC cells, to identify the cytokines involved in the signaling pathway
      and to elucidate the molecular mechanism of this pathway in OSCC cells. MTS, flow
      cytometry and ELISA assay were used to evaluate T-cell immune responses, cancer
      cell proliferation and pro-inflammatory cytokine secretion, respectively. Western
      blot analysis, EMSA and ChIP assay were employed to detect the activity of the NF
      kappaB and AP-1 signaling pathways. A marked response was observed when T-cells
      were co-cultured with supernatants from CpG-ODN-treated OSCC cells. This response
      was characterized by increased CD4+ and CD8+ T-cell proliferation and an increase
      in IFN-gamma production by the CD4+ T-cell population. Treatment of OSCC cells
      with CpG-ODN resulted in an increase in IL-6 secretion as well as an increase in
      AP-1 binding activity to the IL-6 promoter. Moreover, blockage of the TLR-9/AP-1
      pathway significantly decreased IL-6 expression and T-cell immune response. In
      human OSCC, the TLR-9 pathway, when stimulated by CpG-ODNs, promotes a T-cell
      immune response mediated by AP-1-activated IL-6 secretion. Although the complete
      molecular mechanism has yet to be understood, these findings provide evidence
      linking tumor cell activities to immune system responses. In addition, the TLR
      9/AP-1/IL-6 pathway provides new therapeutic targets for the prevention and
      treatment of OSCC. 

PMID- 24676674
TI  - Spinal lesions and retropharyngeal fluid in an immunocompetent patient. Spinal
      tuberculosis (TB): Pott disease.

PMID- 24676673
TI  - Assessment of the risks for human health of adenoviruses, hepatitis A virus,
      rotaviruses and enteroviruses in the Buffalo River and three source water dams in
      the Eastern Cape.
AB  - Buffalo River is an important water resource in the Eastern Cape Province of
      South Africa. The potential risks of infection constituted by exposure to human
      enteric viruses in the Buffalo River and three source water dams along its course
      were assessed using mean values and static quantitative microbial risk assessment
      (QMRA). The daily risks of infection determined by the exponential model [for
      human adenovirus (HAdV) and enterovirus (EnV)] and the beta-Poisson model (for
      hepatitis A virus (HAV) and rotavirus (RoV)) varied with sites and exposure
      scenario. The estimated daily risks of infection values at the sites where the
      respective viruses were detected, ranged from 7.31 * 10(-3) to 1 (for HAdV), 4.23
      * 10(-2) to 6.54 * 10(-1) (RoV), 2.32 * 10(-4) to 1.73 * 10(-1) (HAV) and 1.32 *
      10(-4) to 5.70 * 10(-2) (EnV). The yearly risks of infection in individuals
      exposed to the river/dam water via drinking, recreational, domestic or
      irrigational activities were unacceptably high, exceeding the acceptable risk of
      0.01% (10(-4) infection/person/year), and the guideline value used as by several
      nations for drinking water. The risks of illness and death from infection ranged
      from 6.58 * 10(-5) to 5.0 * 10(-1) and 6.58 * 10(-9) to 5.0 * 10(-5),
      respectively. The threats here are heightened by the high mortality rates for
      HAV, and its endemicity in South Africa. Therefore, we conclude that the Buffalo
      River and its source water dams are a public health hazard. The QMRA presented
      here is the first of its kinds in the Eastern Cape Province and provides the
      building block for a quantitatively oriented local guideline for water quality
      management in the Province.

PMID- 24676675
TI  - Silent (clinically nonfunctioning) pituitary adenomas.
AB  - Silent, or clinically nonfunctioning, pituitary adenomas can arise from any
      anterior pituitary cell type. Some are "clinically silent" in that they result in
      a supranormal serum concentration of the hormonal product of the cell type from
      which the adenoma arose but do not cause the clinical manifestations typical of
      excessive levels of that hormone. Others are "totally silent" in that they result
      in neither hormonal excess nor clinical manifestations. Gonadotroph and null cell
      adenomas are the most prevalent types and are typically silent. Somatotroph and
      corticotroph adenomas typically cause clinical syndromes but occasionally are
      clinically or totally silent. Those that are silent are usually larger and grow
      more aggressively than those that cause clinical syndromes. Silent adenomas are
      usually not discovered until they become very large and cause neurologic defects,
      such as visual impairment, but are also often discovered incidentally when
      neuroimaging is performed for another reason. Silent adenomas may become, rarely,
      clinically apparent over time. The diagnosis of a silent pituitary adenoma begins
      with the detection of a sellar mass by MRI. Biochemical testing can identify the
      adenoma cell type in those that are clinically silent. Silent adenomas that cause
      neurologic deficits require transsphenoidal surgery, but those that do not can be
      followed by MRI. Residual or recurrent disease is treated by radiation therapy,
      which is usually effective in preventing further growth but results in hormonal
      deficiencies in about half of patients. Dopamine agonists and somatostatin
      analogs are usually ineffective, but occasionally have been associated with
      reduced adenoma size. 

PMID- 24676677
TI  - Evaluation of angiogenesis in non-small cell lung carcinoma by CD34
      immunohistochemistry.
AB  - The objective of the study was to investigate angiogenesis in non-small lung
      cancer by measuring the expression of CD34. Immunohistochemistry was used to
      detect CD34 at the endothelial cell surface in 81 surgically resected non-small
      cell lung cancer specimens. CD34 immunohistochemistry had high specificity and
      sensitivity with minimal background, which enabled efficient identification of
      CD34-positive staining. Statistical analysis showed that increased microvessel
      density (MVD) was closely correlated to tumor progression as reflected by the
      clinical stage (P < 0.05). However, MVD was not significantly associated with
      lymph node metastasis and other clinical and pathological features (P > 0.05). In
      conclusion, microvascular density may play an important role in the development
      and progression of lung cancer.

PMID- 24676676
TI  - Appropriate and necessary oral care for people with cancer: guidance to obtain
      the right oral and dental care at the right time.
AB  - PURPOSE: The identification of experienced and knowledgeable dental specialists
      to provide appropriate oral care for cancer patients, as well as the integration
      of this care within general oncology management, may be a challenge. This paper
      discusses the general and additional requirements for dental care providers to
      support the cancer patient and provide prevention and/or treatment for oral
      complications of cancer therapy. METHODS: We performed a literature review of
      specific issues regarding the oral cavity and adjacent structures in the cancer
      patient, including detection and early diagnosis of oral malignancy. We
      incorporated the systemic effects of cancer and its therapy that affect oral
      disease and treatment. We present a summary of how to seek expert dental care for
      cancer patients and for referral from the dental and medical community. RESULTS:
      Due to the complexity conferred by the disease and its treatment, cancer patients
      require educated, experienced dentists for treatment and/or prevention of oral
      related morbidity. Correct diagnosis and evidence-based prophylactic and
      therapeutic oral care can significantly improve patient quality of life and
      reduce morbidity and healthcare costs. CONCLUSIONS: The knowledge and expertise
      of dental professionals regarding prevention/treatment of complications and
      secondary malignant lesions in cancer patients are critical. Integration of oral
      care with the oncology care and in survivors requires effective communication
      between dental and medical providers beginning ideally at diagnosis. These
      clinicians may be identified at the cancer center, nearby hospital dental
      programs, and, less commonly, in the community.

PMID- 24676678
TI  - Activated human hepatic stellate cells promote growth of human hepatocellular
      carcinoma in a subcutaneous xenograft nude mouse model.
AB  - Tumor cell microenvironment defines cancer development, also in hepatocellular
      carcinoma (HCC). Hepatic stellate cells (HSCs) are believed to be the key
      contributors to tumor microenvironment in HCC, yet their precise role in cancer
      progression is still unclear. The aim of this study was to determine the effect
      of human HSCs on progression of HCC using a subcutaneous xenograft nude mouse
      model. Nude mice were stratified to receive subcutaneous injections of human HCC
      cell line HepG2 and human HSC line LX-2 (HepG2 + LX-2), HepG2 alone, LX-2 alone,
      or phosphate-buffered saline. Tumor growth was assessed by measuring tumor size.
      After 30 days, final tumor size, weight, and histology were assessed. Compared
      with mice that were only injected HepG2 cells, mice injected with HepG2 + LX-2
      exhibited more rapid tumor growth, increased tumor size and weight, higher tumor
      cell numbers due to increased proliferation and reduced apoptosis, increased
      fibrotic bands containing LX-2 cells, and increased tumor angiogenesis. In
      conclusion, HSCs play a significant role in promotion of HCC growth.

PMID- 24676679
TI  - The role of the QseC quorum-sensing sensor kinase in epinephrine-enhanced
      motility and biofilm formation by Escherichia coli.
AB  - Biofilms play a pivotal role in infections related to devices. Biofilm formation
      in Escherichia coli is mediated by the quorum-sensing E. coli regulator C (QseC),
      the histidine sensor kinase that can sense epinephrine (EPI)/norepinephrine (NE).
      In this study, we evaluate the role of the QseC quorum-sensing sensor kinase in
      epinephrine-enhanced motility and biofilm formation by E. coli. An E. coli MC1000
      qseC mutant was constructed. We investigated the role of the QseC in the
      formation of biofilms on the surface of medical-grade polyvinyl chloride using
      the E. coli K-12 MC1000 strain as well as a corresponding qseC mutant. Addition
      of EPI/NE increased biofilm formation by wild-type K-12 MC1000 but not by the
      isogenic qseC mutant. Scanning confocal laser microscopy corroborated these
      results by showing that EPI/NE addition significantly increased biofilm's
      thickness. As expected, the addition of EPI/NE to the qseC mutant, which lacks
      the ability to sense the hormones, failed to stimulate biofilm formation. Since
      EPI/NE addition increased bacterial motility, we proposed that their stimulatory
      effects on biofilm formation occur by enhancing bacterial motility and altering
      biofilm architecture. We also found that EPI/NE regulate motility and the biofilm
      phenotype via QseC, as motility was diminished and biofilm formation was
      significantly decreased in a qseC deletion mutant. These results indicate that
      EPI/NE induce E. coli biofilm formation on the surface of polyvinyl chloride
      through QseC. Cross-talk between E. coli (quorum sensing) and host hormones may
      explain the pathogen-caused opportunistic infections that occur in patients with
      prosthetic devices used during hormone level fluctuations in the host.

PMID- 24676682
TI  - External beam radiation therapy for recalcitrant dermatitis.

PMID- 24676680
TI  - SPARC expression is negatively correlated with clinicopathological factors of
      gastric cancer and inhibits malignancy of gastric cancer cells.
AB  - Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein which
      plays multiple roles in different types of cancer. Our previous study showed that
      SPARC overexpression inhibited the growth and angiogenesis of tumors, and reduced
      expression of vascular endothelial growth factor (VEGF). However, the
      relationship between SPARC expression and clinicopathological factors of gastric
      cancer (GC) is controversial, and the role of SPARC in GC remains unclear. We
      evaluated expression of SPARC in 65 human GC tissues using immunohistochemistry
      (IHC). The results indicated that SPARC expression was negatively correlated with
      clinicopathological factors of GC. In vitro assay showed that SPARC
      overexpression decreased proliferation and clonogenicity by suppressing CD44
      expression. In addition, SPARC overexpression inhibited VEGF induced
      proliferation and arrested cell cycle of GC cells by reducing the activation of
      VEGFR2, ERK1/2 and AKT signaling pathways. SPARC suppressed the invasion and
      migration of GC by reducing MMP-7, MMP-9, N-cadherin, Sp1 and p-ERK1/2
      expression. In the in vivo assay, cancer metastasis mouse models were established
      by tail vein injection. The results revealed that the lung metastases of SPARC
      overexpressing GC cells in the mice were much fewer than those of control cells.

PMID- 24676684
TI  - ALMOST: an all atom molecular simulation toolkit for protein structure
      determination.
AB  - Almost (all atom molecular simulation toolkit) is an open source computational
      package for structure determination and analysis of complex molecular systems
      including proteins, and nucleic acids. Almost has been designed with two primary
      goals: to provide tools for molecular structure determination using various types
      of experimental measurements as conformational restraints, and to provide methods
      for the analysis and assessment of structural and dynamical properties of complex
      molecular systems. The methods incorporated in Almost include the determination
      of structural and dynamical features of proteins using distance restraints
      derived from nuclear Overhauser effect measurements, orientational restraints
      obtained from residual dipolar couplings and the structural restraints from
      chemical shifts. Here, we present the first public release of Almost, highlight
      the key aspects of its computational design and discuss the main features
      currently implemented. Almost is available for the most common Unix-based
      operating systems, including Linux and Mac OS X. Almost is distributed free of
      charge under the GNU Public License, and is available both as a source code and
      as a binary executable from the project web site at http://www.open-almost.org.
      Interested users can follow and contribute to the further development of Almost
      on http://sourceforge.net/projects/almost.

PMID- 24676683
TI  - Involvement of orexin-A neurons but not melanin-concentrating hormone neurons in
      the short-term regulation of food intake in rats.
AB  - In order to elucidate the involvement of melanin-concentrating hormone (MCH) and
      orexin-A (ORX-A) neurons of the perifornical/lateral hypothalamic areas (PF/LH)
      in the regulation of food intake induced by acutely reduced glucose availability,
      we examined the food intake response and c-Fos expression in the MCH and ORX-A
      neurons in the PF/LH during 2-deoxy-D-glucose (2DG)-induced glucoprivation (400
      mg/kg; i.v.) and systemic insulin-induced hypoglycemia (5 U/kg; s.c.) in male
      Wistar rats. The administration of both 2DG and insulin stimulated food intake
      and induced c-Fos expression in the ORX-A neurons corresponding to food intake,
      but not in the MCH neurons. These data indicate that ORX-A neurons, but not MCH
      neurons, play a role in the short-term regulation of food intake, and that the
      input signals for the neurons containing MCH and ORX-A are different, and these
      neurons play different roles in the regulation of feeding behavior.

PMID- 24676685
TI  - Intraclass diversification of immunoglobulin heavy chain genes in the African
      lungfish.
AB  - Lungfish (Dipnoi) are the closest living relatives to tetrapods, and they
      represent the transition from water to land during vertebrate evolution. Lungfish
      are armed with immunoglobulins (Igs), one of the hallmarks of the adaptive immune
      system of jawed vertebrates, but only three Ig forms have been characterized in
      Dipnoi to date. We report here a new diversity of Ig molecules in two African
      lungfish species (Protopterus dolloi and Protopterus annectens). The African
      lungfish Igs consist of three IgMs, two IgWs, three IgNs, and an IgQ, where both
      IgN and IgQ originated evidently from the IgW lineage. Our data also suggest that
      the IgH genes in the lungfish are organized in a transiting form from clusters
      (IgH loci in cartilaginous fish) to a translocon configuration (IgH locus in
      tetrapods). We propose that the intraclass diversification of the two primordial
      gnathostome Ig classes (IgM and IgW) as well as acquisition of new isotypes (IgN
      and IgQ) has allowed lungfish to acquire a complex and functionally diverse Ig
      repertoire to fight a variety of microorganisms. Furthermore, our results support
      the idea that "tetrapod-specific" Ig classes did not evolve until the vertebrate
      adaptation to land was completed ~360 million years ago. 

PMID- 24676686
TI  - MHC polymorphism in Caribbean African green monkeys.
AB  - African green monkeys (AGM) are among the most widely used nonhuman primate
      models used in various fields of medical research. One species of AGM that
      originated from West Africa, Chlorocebus sabaeus, was introduced three centuries
      ago in the Caribbean islands. We present here a systematic study of the major
      histocompatibility complex (MHC) polymorphism of Caribbean AGM which is currently
      frequently used as an animal model. We studied 54 animals originated from
      Barbados (N=25) or Saint Kitts (N=29). The MHC polymorphism was characterized by
      means of 17 MHC microsatellites spread across MHC and DRB genotyping by DGGE
      sequencing. We defined nine frequent MHC haplotypes of which two were found in
      the two insular populations suggesting either past exchanges between the two
      populations or a common origin of the founders of the two populations. By the
      analysis of a previously described EST library, we characterized 38 MHC cDNA
      sequences (17 class I and 21 class II). In conclusion, we characterized for the
      first time the MHC polymorphism of Barbados and Saint Kitts AGM. We found a
      restricted polymorphism due to a founding effect, which is responsible for a
      strong bottleneck. The poorness of MHC polymorphism observed in the Caribbean AGM
      populations is similar to that observed in the Mauritian cynomolgus macaque
      population.

PMID- 24676687
TI  - Inactivation of protein-phosphatase 2A causing hyperphosphorylation of
      autoantigenic paraprotein targets in MGUS/MM is due to an exchange of its
      regulatory subunits.
AB  - Hyperphosphorylated paratarg-7 (pP-7) carrier state is the strongest molecularly
      defined risk factor for monoclonal gammopathy of undetermined significance
      (MGUS), multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM). pP-7 is
      inherited as autosomal-dominant trait and depending on the ethnic background is
      found in over one-third of MGUS/MM patients. P-7, which is the antigenic
      paraprotein target in these patients, is hyperphosphorylated at serine17. P-7
      hyperphosphorylation can be induced in wild-type P-7 (wtP-7) carriers by PKCzeta
      and reverted by protein-phosphatase 2A (PP2A). Here we show that
      dephosphorylation of pP-7 is defective in pP-7 carriers due to inactivation of
      the PP2A by substitution of the regulatory B55delta subunit with B56gamma3. In
      lymphoblastoid cell lines from pP-7 carriers, transfection of recombinant
      B55delta or treatment with ceramide led to a partial reconstitution of PP2A
      activity and dephosphorylation of pP-7 to wtP7. Similar results were observed
      with other previously reported autoantigenic paraproteins targets. In conclusion,
      the mechanisms responsible for the defective dephosphorylation and maintaining
      the hyperphosphorylated state of P-7 and other autoantigenic paraprotein targets
      have been elucidated, facilitating the identification of the genetic basis
      underlying this phenomenon which is obviously common in the pathogenesis of
      MGUS/MM/WM and not restricted to pP-7 cases.

PMID- 24676688
TI  - Presence of non-O157 Shiga toxin-producing Escherichia coli, enterotoxigenic E.
      coli, enteropathogenic E. coli and Salmonella in fresh beetroot (Beta vulgaris
      L.) juice from public markets in Mexico.
AB  - BACKGROUND: Unpasteurized juice has been associated with foodborne illness
      outbreaks for many years. Beetroot is a vegetable grown all over the world in
      temperate areas. In Mexico beetroot is consumed cooked in salads or raw as fresh
      unpasteurized juices. No data about the microbiological quality or safety of
      unpasteurized beetroot juices are available. Indicator bacteria, diarrheagenic
      Escherichia coli pathotypes (DEP) and Salmonella frequencies were determined for
      fresh unpasteurized beetroot juice from restaurants. RESULTS: One hundred
      unpasteurized beetroot juice samples were collected from public markets in
      Pachuca, Mexico. Frequencies in these samples were 100%, 75%, 53%, 9% and 4% of
      positive samples, for coliform bacteria, fecal coliforms, E. coli, DEP and
      Salmonella, respectively. Identified DEP included enterotoxigenic E. coli (ETEC),
      enteropathogenic E. coli (EPEC) and non-O157 Shiga toxin-producing E. coli
      (STEC). Identified Salmonella serotypes included Typhimurium and Enteritidis.
      CONCLUSION: This is the first report of microbiological quality and atypical
      EPEC, ETEC, non-O157 STEC and Salmonella isolation from fresh raw beetroot juice
      in Mexico. Fresh raw beetroot juice from markets is very probably an important
      factor contributing to the endemicity of atypical EPEC, ETEC, non-O157 STEC and
      Salmonella-related gastroenteritis in Mexico.

PMID- 24676689
TI  - A mixture of transition models for heterogeneous longitudinal ordinal data: with
      applications to longitudinal bacterial vaginosis data.
AB  - Markov models used to analyze transition patterns in discrete longitudinal data
      are based on the limiting assumption that individuals follow the common
      underlying transition process. However, when one is interested in diseases with
      different disease or severity subtypes, explicitly modeling subpopulation
      specific transition patterns may be appropriate. We propose a model which
      captures heterogeneity in the transition process through a finite mixture model
      formulation and provides a framework for identifying subpopulations at different
      risks. We apply the procedure to longitudinal bacterial vaginosis study data and
      demonstrate that the model fits the data well. Further, we show that under the
      mixture model formulation, we can make the important distinction between how
      covariates affect transition patterns unique to each of the subpopulations and
      how they affect which subgroup a participant will belong to. Practically,
      covariate effects on subpopulation-specific transition behavior and those on
      subpopulation membership can be interpreted as effects on short-term and long
      term transition behavior. We further investigate models with higher-order
      subpopulation-specific transition dependence.

PMID- 24676694
TI  - Comparison of two oral contraceptive forms containing cyproterone acetate and
      drospirenone in the treatment of patients with polycystic ovary syndrome: a
      randomized clinical trial.
AB  - PURPOSE: To compare the effects of combined oral contraceptives (OCs) containing
      cyproterone acetate and drospirenone in the treatment of polycystic ovary
      syndrome (PCOS). METHODS: Fifty-two patients with PCOS were randomized in two
      groups: group A (n = 26) received 0.035 mg ethinyl estradiol + 2 mg cyproterone
      acetate and group B (n = 26) received 0.03 mg ethinyl estradiol + 3 mg
      drospirenone-containing OCs for 12 months. Baseline clinical features including
      body mass index, waist to hip ratio (WHR), and modified Ferriman-Gallwey (mFG)
      score were noted. Baseline biochemical parameters included androgen profile,
      carbohydrate metabolism, lipid profile, and oxidative stress. The percentages of
      changes for all parameters were compared. RESULTS: The groups were comparable
      regarding the baseline characteristics. WHR decreased significantly from baseline
      (-4 % [-31 to 35]) in group B when compared to group A (0 % [-11 to 14]) (P =
      0.033). The total mFG score decreased significantly from baseline (-35 % [-71 to
      10]) in group A when compared to group B (-18 % [-72 to 30]) (P = 0.035). Changes
      in androgen hormone profile were comparable except DHEA-SO4 (-32 % [-53 to 15] in
      group B vs. -10 % [-49 to 63] in group A; P = 0.046). The effects of the drugs
      were similar regarding carbohydrate metabolism, lipid profile, and oxidative
      stress parameters. CONCLUSIONS: Cyproterone acetate containing OCs seem to be
      more effective to treat clinical hirsutism in patients with PCOS after 12 months
      of treatment.

PMID- 24676695
TI  - Juvenile stroke in combined syndrome of hereditary hemorrhagic telangiectasia and
      juvenile polyposis.

PMID- 24676696
TI  - Hesperidin attenuates oxidative and neuronal damage caused by global cerebral
      ischemia/reperfusion in a C57BL/J6 mouse model.
AB  - The aim of this study was to determine the effects of hesperidin (HP) on neuronal
      damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in
      C57BL/J6 mice. For this purpose, a total of 40 mice were divided equally into
      four groups: (1) sham-operated (SH), (2) global cerebral I/R, (3) HP, and (4)
      HP+I/R. The SH group was used as a control. In the I/R group, the bilateral
      carotid arteries were clipped for 15 min, and the mice were treated with vehicle
      for 10 days. In the HP group, mice were administered HP (100 mg/kg) for 10 days
      without carotid occlusion. In the HP+I/R group, the I/R model was applied to the
      mice exactly as in the I/R group, and they were then treated with 100 mg/kg HP
      for 10 days. Cerebral I/R significantly induced oxidative stress via an increase
      in lipid peroxidation and a decrease in the components of the antioxidant defense
      system. Furthermore, cerebral I/R increased the incidence of histopathological
      damage and apoptosis in brain tissue. HP treatment significantly reversed the
      oxidative effects of I/R and inhibited the development of neurodegenerative
      histopathology. Therefore, the current study demonstrates that HP treatment
      effectively prevents oxidative and histological damage in the brain caused by
      global I/R. In this context, the beneficial effects of HP are likely a result of
      its strong antioxidant and free radical-scavenging properties. HP may be an
      useful treatment to attenuate the negative effects of global cerebral I/R.

PMID- 24676697
TI  - Combined bilateral absence of trochlear and abducens nerve.

PMID- 24676698
TI  - Transplanting a fibrogenic microbiota.

PMID- 24676699
TI  - Substantiation of 25 kGy radiation sterilization dose for banked air dried
      amniotic membrane and evaluation of personnel skill in influencing finished
      product bioburden.
AB  - Preparation of amniotic membrane (AM) by air drying method followed by radiation
      sterilization is simple and valuable approach; sterility and quality of the final
      AM product are depending on the quality management system at the tissue bank.
      Validation and substantiation of radiation sterilization dose (RSD) for tissue
      allografts is an essential step for the development and validation of the
      standard operating procedures (SOP). Application of SOP is perfectly relying on
      trained staff. Skills differences among personnel involved in AM preparation
      could have an effect on microbiological quality of the finished product and
      subsequently on the RSD required. AM were processed by four different couples of
      the tissue bank technicians. The AM grafts were randomly selected and subjected
      to bioburden test to validate and substantiate the 25 kGy RSD. Bioburden test for
      AM grafts were also useful to evaluate the skill of the tissue bank technicians
      and thus, to validate the current SOP for air dried AM. Moreover, the effect of
      placental source on bioburden counts on AM grafts was assessed. Substantiation of
      the 25 kGy RSD at a sterility assurance level of 10(-1), and sample item portion
      = 1, was carried out using Method VD max (25) of the International Organization
      for Standardization, document no. 11137-2 (ISO in Sterilization of healthcare
      products-radiation-part 2: establishing the sterilization dose, Method VDmax
      substantiation of 25 kGy or 15 kGy as the sterilization dose, International
      Standard Organization, 2006). The results showed that there were no significant
      differences in the bioburdens of the four batches (alpha = 1 %), this means no
      significant differences in the skill of the four couples of the tissue bank
      technicians in terms of their ability to process AM according to the air dried AM
      SOP. The 25 kGy RSD was validated and substantiated as a valid sterilization dose
      for the AM prepared with the current established SOP at the Biotechnology
      Research Center experimental tissue bank. The donor's type of delivery, normal or
      caesarean, showed no significant effect on the levels of microbial counts on the
      tested AMs (alpha = 1 %). 

PMID- 24676701
TI  - Effects of repeated low-dose exposure of the nerve agent VX on monoamine levels
      in different brain structures in mice.
AB  - In a previous report, alterations of the serotonin metabolism were previously
      reported in mice intoxicated with repeated low doses of soman. In order to better
      understand the effects induced by repeated low-dose exposure to organophosphorus
      compounds on physiological and behavioural functions, the levels of endogenous
      monoamines (serotonin and dopamine) in different brain areas in mice intoxicated
      with sublethal dose of (O-ethyl-S-[2(di-isopropylamino) ethyl] methyl
      phosphonothioate) (VX) were analysed by HPLC method with electrochemical
      detection. Animals were injected once a day for three consecutive days with 0.10
      LD50 of VX (5 MUg/kg, i.p). Neither severe signs of cholinergic toxicity nor
      pathological changes in brain tissue of exposed animals were observed.
      Cholinesterase (ChE) activity was only inhibited in plasma (a maximum of 30%
      inhibition 24 h after the last injection of VX), but remained unchanged in the
      brain. Serotonin and dopamine (DA) metabolism appeared significantly modified.
      During the entire period of investigation, at least one of the three parameters
      investigated (i.e. DA and DOPAC levels and DOPAC/DA ratio) was modified. During
      the toxic challenge, an increase of the serotonin metabolism was noted in
      hippocampus (HPC), hypothalamus/thalamus, pons medulla and cerebellum (CER). This
      increase was maintained 4 weeks after exposure in HPC, pons medulla and CER
      whereas a decrease in cortex 3 weeks after the toxic challenge was observed. The
      lack of correlation between brain ChE activity and neurochemical outcomes points
      out to independent mechanisms. The involvement in possibly long-lasting
      behavioural disorders is discussed.

PMID- 24676703
TI  - Combination of dasatinib and gemcitabine reduces the ALDH1A1 expression and the
      proliferation of gemcitabine-resistant pancreatic cancer MIA PaCa-2 cells.
AB  - Gemcitabine-based chemotherapy is the standard for treatment of pancreatic
      cancer; however, intrinsic and acquired resistance to gemcitabine commonly
      occurs. Aldehyde dehydrogenase 1A1 (ALDH1A1), one of the characteristic features
      of tumor-initiating and/or cancer stem cell (CSC) properties, is important in
      both intrinsic and acquired resistance to gemcitabine. In this study, we
      investigated the effectiveness of dasatinib, an SRC inhibitor, and gemcitabine
      combination to inhibit the survivals of parental (MIA PaCa-2/P) and gemcitabine
      resistant (MIA PaCa-2/GR) cell lines. In MIA PaCa-2/GR cells, the levels of
      phospho-SRC and ALDH1A1 were increased compared to MIA PaCa-2/P cells. Inhibition
      of SRC by dasatinib or siRNA synergistically enhanced gemcitabine-induced anti
      proliferative effects and induced apoptotic cell death in these cells.
      Furthermore, combination of SRC inhibition (either by dasatinib or siRNA) and
      gemcitabine significantly decreased the levels of ALDH1A1 expression. These
      results suggest that dasatinib and gemcitabine combination may be a potential
      therapeutic strategy to overcome gemcitabine resistance by decreasing the levels
      of ALDH1A1 expression. 

PMID- 24676702
TI  - Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and
      physiological deficits: the roles of GABAA receptors in adolescence.
AB  - Fetal alcohol exposure (FAE) can lead to a variety of behavioral and
      physiological disturbances later in life. Understanding how alcohol (ethanol,
      EtOH) affects fetal brain development is essential to guide the development of
      better therapeutics for FAE. One of EtOH's many pharmacological targets is the
      gamma-aminobutyric acid type A receptor (GABAAR), which plays a prominent role in
      early brain development. Acute EtOH potentiates inhibitory currents carried by
      certain GABAAR subtypes, whereas chronic EtOH leads to persistent alterations in
      GABAAR subunit composition, localization and function. We recently introduced a
      flavonoid compound, dihydromyricetin (DHM), which selectively antagonizes EtOH's
      intoxicating effects in vivo and in vitro at enhancing GABAAR function as a
      candidate for alcohol abuse pharmacotherapy. Here, we studied the effect of FAE
      on physiology, behavior and GABAAR function of early adolescent rats and tested
      the utility of DHM as a preventative treatment for FAE-induced disturbances.
      Gavage administration of EtOH (1.5, 2.5, or 5.0 g/kg) to rat dams on day 5, 8,
      10, 12, and 15 of pregnancy dose-dependently reduced female/male offspring ratios
      (largely through decreased numbers of female offspring) and offspring body
      weights. FAE (2.5 g/kg) rats tested on postnatal days (P) 25-32 also exhibited
      increased anxiety and reduced pentylenetetrazol (PTZ)-induced seizure threshold.
      Patch-clamp recordings from dentate gyrus granule cells (DGCs) in hippocampal
      slices from FAE (2.5 g/kg) rats at P25-35 revealed reduced sensitivity of
      GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and tonic current
      (Itonic) to potentiation by zolpidem (0.3 MUM). Interestingly, potentiation of
      mIPSCs by gaboxadol increased, while potentiation of Itonic decreased in DGCs
      from FAE rats. Co-administration of EtOH (1.5 or 2.5 g/kg) with DHM (1.0 mg/kg)
      in pregnant dams prevented all of the behavioral, physiological, and
      pharmacological alterations observed in FAE offspring. DHM administration alone
      in pregnant rats had no adverse effect on litter size, progeny weight, anxiety
      level, PTZ seizure threshold, or DGC GABAAR function. Our results indicate that
      FAE induces long-lasting alterations in physiology, behavior, and hippocampal
      GABAAR function and that these deficits are prevented by DHM co-treatment of EtOH
      exposed dams. The absence of adverse side effects and the ability of DHM to
      prevent FAE consequences suggest that DHM is an attractive candidate for
      development as a treatment for prevention of fetal alcohol spectrum disorders. 

PMID- 24676706
TI  - PHOTO QUIZ. Enterobius vermicularis appendicitis.

PMID- 24676704
TI  - Evaluation of properties of the Vestibular Disorders Activities of Daily Living
      Scale (Brazilian version) in an elderly population.
AB  - BACKGROUND: The Vestibular Disorders Activities of Daily Living Scale (VADL) is
      considered an important subjective assessment to evaluate patients suffering from
      dizziness and imbalance. Although frequently used, its metric characteristics
      still require further investigation. OBJECTIVE: This paper aims to analyze the
      psychometric properties of the Brazilian version of the VADL in an elderly
      population. METHOD: The sample comprises patients (>= 65 years old) with chronic
      dizziness resulting from vestibular disorders. For discriminant analysis,
      patients were compared to healthy subjects. All subjects answered the VADL-Brazil
      by interview. To examine the VADL validity, patients filled out the Dizziness
      Handicap Inventory (DHI) and the ABC scale and were tested on the Dynamic Gait
      Index (DGI). To evaluate the VADL responsiveness, 20 patients were submitted to
      rehabilitation. RESULTS: Patients (n=140) had a VADL total score of 4.1 +/- 1.6
      points. Healthy subjects scored significantly less than patients in all the
      subscales and in the VADL total score. The VADL-Brazil was weakly correlated with
      the DHI and moderately to the ABC scale and the DGI. Instead of the original 3
      subscales, factor analysis resulted in 6 factors. The VADL was capable of
      detecting changes after rehabilitation, which means that the instrument has
      responsiveness. CONCLUSIONS: This study provided more data about the psychometric
      properties and usefulness of the VADL-Brazil. The use of such a reliable and
      valid instrument increases the knowledge about disability in patients with
      vestibular disorders.

PMID- 24676705
TI  - Influence of aging on isometric muscle strength, fat-free mass and
      electromyographic signal power of the upper and lower limbs in women.
AB  - BACKGROUND: Aging is a multifactorial process that leads to changes in the
      quantity and quality of skeletal muscle and contributes to decreased levels of
      muscle strength. OBJECTIVE: This study sought to investigate whether the
      isometric muscle strength, fat-free mass (FFM) and power of the electromyographic
      (EMG) signal of the upper and lower limbs of women are similarly affected by
      aging. METHOD: The sample consisted of 63 women, who were subdivided into three
      groups (young (YO) n=33, 24.7 +/- 3.5 years; middle age (MA) n=15, 58.6 +/- 4.2
      years; and older adults (OA). n=15, 72.0 +/- 4.2 years). Isometric strength was
      recorded simultaneously with the capture of the electrical activity of the flexor
      muscles of the fingers and the vastus lateralis during handgrip and knee
      extension tests, respectively. FFM was assessed using dual-energy X-ray
      absorptiometry. RESULTS: The handgrip strength measurements were similar among
      groups (p=0.523), whereas the FFM of the upper limbs was lower in group OA
      compared to group YO (p=0.108). The RMSn values of the hand flexors were similar
      among groups (p=0.754). However, the strength of the knee extensors, the FFM of
      the lower limbs and the RMSn values of the vastus lateralis were lower in groups
      MA (p=0.014, p=0.006 and p=0.013, respectively) and OA (p=0.000, p=0.000 and
      p<0.000, respectively) compared to group YO. CONCLUSIONS : The results of this
      study demonstrate that changes in isometric muscle strength in MLG and
      electromyographic activity of the lower limbs are more pronounced with the aging
      process of the upper limb.

PMID- 24676712
TI  - Opposite effects of the gap junction blocker octanol on focal cerebral ischemia
      occluded for different durations.
AB  - Protectants and executioners have been demonstrated to be used by gap junctions
      in focal cerebral ischemia. Certain researchers hypothesized that the opposite
      role of gap junctions may be associated with the injury extent, which has been
      demonstrated to be highly correlated with occlusion duration. In order to examine
      this hypothesis directly, the effects of octanol, a frequently used drug, were
      examined to investigate the role of gap junctions, in rats following middle
      cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion,
      respectively. Octanol significantly reduced the infarct volume following 2 h of
      occlusion concomitant with lower neurological deficits, whereas it enlarged the
      infarct volume following 30 min of occlusion. Consistently, octanol attenuated
      the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the
      hippocampal CA1 region following 2 h of occlusion, while opposite effects were
      observed for 30 min of occlusion. Further immunohistochemical studies
      demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic
      protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein)
      was downregulated following 2 h of occlusion in the octanol group compared with
      the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2
      protein concomitant with increased Bax protein following 30 min of occlusion.
      These results indicated that the gap junction blocker octanol can protect against
      ischemic injury following long-term occlusion, however, can aggravate ischemic
      injury following short-term occlusion.

PMID- 24676714
TI  - Use of simulation boot camps to train junior otolaryngology residents: a
      resident's testimonial.

PMID- 24676713
TI  - Stem cell research funding policies and dynamic innovation: a survey of open
      access and commercialization requirements.
AB  - This article compares and contrasts the pressures of both open access data
      sharing and commercialization policies in the context of publicly funded
      embryonic stem cell research (SCR). First, normative guidelines of international
      SCR organizations were examined. We then examined SCR funding guidelines and the
      project evaluation criteria of major funding organizations in the EU, the United
      Kingdom (UK), Spain, Canada and the United States. Our survey of policies
      revealed subtle pressures to commercialize research that include: increased
      funding availability for commercialization opportunities, assistance for
      obtaining intellectual property rights (IPRs) and legislation mandating
      commercialization. In lieu of open access models, funders are increasingly opting
      for limited sharing models or "protected commons" models that make the research
      available to researchers within the same region or those receiving the same
      funding. Meanwhile, there still is need for funding agencies to clarify and
      standardize terms such as "non-profit organizations" and "for-profit research,"
      as more universities are pursuing for-profit or commercial opportunities. 

PMID- 24676716
TI  - Confusion in reporting pulmonary diffusing capacity for nitric oxide and the
      alveolar-capillary membrane conductance for nitric oxide.

PMID- 24676718
TI  - Effects of selective MMP-13 inhibition in squamous cell carcinoma depend on
      estrogen.
AB  - Matrix metalloproteinases like MMP-13 cleave and remodel the extracellular matrix
      and thereby play a crucial role in tumor progression in vivo. Using a highly
      selective inhibitor to block MMP-13 protein activity, we demonstrate a striking
      inhibitory effect on invasive tumor growth and vascularization in murine skin
      squamous cell carcinoma (SCC). Therapy outcome critically depends on animal age
      in C57Bl/6 mice and was successful in old female but not in young female mice.
      Treatment success was recovered by ovariectomy in young and abolished by 17beta
      estradiol supplementation in old mice, suggesting a hormone dependent inhibitor
      effect. Responsiveness of the tumorigenic keratinocytes BDVII and fibroblasts to
      17beta-estradiol was confirmed in vitro, where MMP-13 inhibitor treatment led to
      a reduction of cell invasion and vascular endothelial growth factor (VEGF)
      release. This correlated well with a less invasive and vascularized tumor in
      treated mice in vivo. 17beta-estradiol supplementation also reduced invasion and
      VEGF release in vitro with no additional reduction on MMP-13 inhibitor treatment.
      This suggests that low 17beta-estradiol levels in old mice in vivo lead to
      enhanced MMP-13 levels and VEGF release, allowing a more effective inhibitor
      treatment compared to young mice. In our study, we present a strong link between
      lower estrogen levels in old female mice, an elevated MMP-13 level, which results
      in a more effective MMP-13 inhibitor treatment in fibroblasts and SCC cells in
      vitro and in vivo.

PMID- 24676719
TI  - Circulating anti-BP180 NC16a and anti-BP230 autoantibodies in patients with
      genital lichen sclerosus do not correlate with disease activity and pruritus.

PMID- 24676720
TI  - [Treatment of fractures of the ankle in the elderly].
AB  - BACKGROUND: Osteoporotic fractures of the ankle were observed three times more
      often in the year 2000 than in the year 1970 and it is predicted that this will
      increase another three times by the year 2030. The most important predictive
      values for ankle fractures in the elderly are smoking, multipharmacy and poor
      mobility. INJURY PATTERNS: Conservative treatment only seems to be successful in
      stable ankle fractures with good surrounding soft tissue. Pronation-abduction
      (PA) fractures most commonly affect elderly females and 90% of the cases present
      as the very unstable type III. Unstable fractures, such as PA type III,
      supination-eversion (SE) and pronation-eversion (PE) fractures type IV can be
      treated better by 2-stage open reduction internal fixation (ORIF). Because the PA
      type III fracture is often associated with dorsal dislocation of the foot it is
      proposed that this type should be classified as type IV, which needs urgent
      surgery to prevent further soft tissue damage. THERAPY: Recommended techniques
      are the K-wire cage or fibula-pro-tibia technique. Locking plates are also
      preferred for stable fracture fixation. According to the recommended preoperative
      computed tomography (CT) scan a Volkmann's fracture should be fixed through a
      posterolateral approach. The additional tibiotarsal internal transfixation should
      remain for 6-8 weeks after ORIF until it is changed to a protective lower leg
      cast after wound healing. An underlying osteoporosis should be diagnosed and
      inpatient treatment of this entity should be initiated by trauma surgeons whereby
      coordination training is also important. CONCLUSION: Due to the increasing number
      of ankle fractures in the elderly particularly in postmenopausal women with
      osteoporosis, the insufficient diagnostics and therapy of osteoporosis and
      because the number of these difficult to treat fractures will increase by a
      factor of 3 by 2030, special surgical techniques and particularly implants are
      necessary for unstable ankle fractures types PA III, SE IV and PE.

PMID- 24676717
TI  - Chromatin dynamics: H3K4 methylation and H3 variant replacement during
      development and in cancer.
AB  - The dynamic nature of chromatin and its myriad modifications play a crucial role
      in gene regulation (expression and repression) during development, cellular
      survival, homeostasis, ageing, and apoptosis/death. Histone 3 lysine 4
      methylation (H3K4 methylation) catalyzed by H3K4 specific histone
      methyltransferases is one of the more critical chromatin modifications that is
      generally associated with gene activation. Additionally, the deposition of H3
      variant(s) in conjunction with H3K4 methylation generates an intricately reliable
      epigenetic regulatory circuit that guides transcriptional activity in normal
      development and homeostasis. Consequently, alterations in this epigenetic circuit
      may trigger disease development. The mechanistic relationship between H3 variant
      deposition and H3K4 methylation during normal development has remained foggy.
      However, recent investigations in the field of chromatin dynamics in various
      model organisms, tumors, cancer tissues, and cell lines cultured without and with
      therapeutic agents, as well as from model reconstituted chromatins reveal that
      there may be different subsets of chromatin assemblage with specific patterns of
      histone replacement executing similar functions. In this light, we attempt to
      explain the intricate control system that maintains chromatin structure and
      dynamics during normal development as well as during tumor development and cancer
      progression in this review. Our focus is to highlight the contribution of H3K4
      methylation-histone variant crosstalk in regulating chromatin architecture and
      subsequently its function.

PMID- 24676721
TI  - In Vitro Antibacterial Mechanism of Action of Crude Garlic (Allium sativum) Clove
      Extract on Selected Probiotic Bifidobacterium Species as Revealed by SEM, TEM,
      and SDS-PAGE Analysis.
AB  - There has been much research on the effects of garlic (Allium sativum) on
      numerous pathogens, but very few, if any, studies on its effect on beneficial,
      probiotic bifidobacteria. We have recently shown that garlic exhibits
      antibacterial activity against bifidobacteria. The mechanism by which garlic
      kills bifidobacteria is yet to be elucidated. This study sought to determine the
      mechanism of action of garlic clove extract on selected Bifidobacterium species
      using scanning and transmission electron microscopy and SDS-PAGE analysis. SEM
      micrographs revealed unusual morphological changes such as cell elongation, cocci
      shaped cells with cross-walls, and distorted cells with bulbous ends. With TEM,
      observed changes included among others, condensation of cytoplasmic material,
      disintegration of membranes, and loss of structural integrity. SDS-PAGE analysis
      did not reveal any differences in whole-cell protein profiles of untreated and
      garlic clove extract-treated cells. The current study is the first to reveal the
      mechanism of action of garlic clove extract on probiotic Bifidobacterium species.
      The results indicate that garlic affects these beneficial bacteria in a manner
      similar to that exhibited in pathogens. These results therefore further highlight
      that caution should be taken especially when using raw garlic and probiotic
      bifidobacteria simultaneously as viability of these bacteria could be reduced by
      allicin released upon crushing of garlic cloves, thereby limiting the health
      benefits that the consumer anticipate to gain from probiotics. 

PMID- 24676722
TI  - Functional Characterization of a c-type Lysozyme from Indian Shrimp
      Fenneropenaeus indicus.
AB  - Lysozyme gene from Fenneropenaeus indicus was cloned, expressed in Escherichia
      coli and characterized. The cDNA consists of 477 base pairs and encodes amino
      acid sequence of 159 residues. F. indicus lysozyme had high identity (98%) with
      Fenneropenaeus merguiensis and Fenneropenaeus chinensis and exhibits low to
      moderate identities with lysozymes of other invertebrates and vertebrates. This
      lysozyme is presumed to be chicken types as it possesses two catalytic and eight
      cysteine residues that are conserved across c-type lysozymes and a c-terminal
      extension, which is a characteristic of lysozymes from marine invertebrates.
      Further, the antimicrobial properties of the recombinant lysozyme from F. indicus
      were determined in comparison with recombinant hen egg white lysozyme. This
      exhibited high activity against a Gram-negative pathogenic bacterium Salmonella
      typhimurium and two fungal strains Pichia pastoris and Saccharomyces cerevisiae
      in turbidimetric assay. Distribution of lysozyme gene and protein in tissues of
      shrimps infected with white spot syndrome virus revealed that the high levels of
      lysozyme are correlated with low and high viral load in abdominal muscle and
      tail, respectively. In conclusion, lysozyme from F. indicus has a broad spectrum
      of antimicrobial properties, which once again emphasizes its role in shrimp
      innate immune response.

PMID- 24676715
TI  - A pragmatic randomized trial of a polypill-based strategy to improve use of
      indicated preventive treatments in people at high cardiovascular disease risk.
AB  - BACKGROUND: Most individuals at high cardiovascular disease (CVD) risk worldwide
      do not receive any or optimal preventive drugs. We aimed to determine whether
      fixed dose combinations of generic drugs ('polypills') would promote use of such
      medications. METHODS: We conducted a randomized, open-label trial involving 623
      participants from Australian general practices. Participants had established CVD
      or an estimated five-year CVD risk of >=15%, with indications for antiplatelet,
      statin and >=2 blood pressure lowering drugs ('combination treatment').
      Participants randomized to the 'polypill-based strategy' received a polypill
      containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol
      50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care'
      continued with separate medications and doses as prescribed by their doctor.
      Primary outcomes were self-reported combination treatment use, systolic blood
      pressure and total cholesterol. RESULTS: After a median of 18 months, the
      polypill-based strategy was associated with greater use of combination treatment
      (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p <
      0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in
      systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total
      cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26). At study end, 17% and
      67% of participants in polypill and usual care groups, respectively, were taking
      atorvastatin or rosuvastatin. CONCLUSION: Provision of a polypill improved self
      reported use of indicated preventive treatments. The lack of differences in blood
      pressure and cholesterol may reflect limited study power, although for
      cholesterol, improved statin use in the polypill group counter-balanced use of
      more potent statins with usual care.

PMID- 24676723
TI  - Lactobacillus pentosus B231 Isolated from a Portuguese PDO Cheese: Production and
      Partial Characterization of Its Bacteriocin.
AB  - Bacteriocin B231 produced by Lactobacillus pentosus, isolated from an artisanal
      raw cow's milk protected designation of origin Portuguese cheese, is a small
      protein with an apparent relative mass of about 5 kDa and active against a large
      number of Listeria monocytogenes wild-type strains, Listeria ivanovii and
      Listeria innocua. Bacteriocin B231 production is highly dependent on the type of
      the culture media used for growth of Lact. pentosus B231. Replacement of glucose
      with maltose yielded the highest bacteriocin production from eight different
      carbon sources. Similar results were recorded in the presence of combination of
      glucose and maltose or galactose. Production of bacteriocin B231 reached maximal
      levels of 800 AU/ml during the stationary phase of growth of Lact. pentosus B231
      in MRS broth at 30  degrees C. Bacteriocin B231 (in cell-free supernatant) was
      sensitive to treatment with trypsin and proteinase K, but not affected by the
      thermal treatment in range of 55-121  degrees C, or freezing (-20  degrees C).
      Bacteriocin production and inhibitory spectrum were evaluated. Gene encoding
      plantaricin S has been detected in the genomic DNA. Virulence potential and
      safety of Lact. pentosus B231 were assessed by PCR targeted the genes gelE, hyl,
      asa1, esp, cylA, efaA, ace, vanA, vanB, hdc1, hdc2, tdc and odc. The Lact.
      pentosus B231 strains harbored plantaricin S gene, while the occurrence of
      virulence, antibiotic resistance and biogenic amine genes was limited to
      cytolysin, hyaluronidase, aggregation substance, adhesion of collagen protein,
      gelatinase, tyrosine decarboxylase and vancomycin B genes.

PMID- 24676724
TI  - Probiotic Potential of Lactobacillus plantarum LD1 Isolated from Batter of Dosa,
      a South Indian Fermented Food.
AB  - Lactobacillus plantarum LD1 was isolated from dosa batter and identified by
      biochemical, physiological and genetic methods. Species level identification was
      done by 16S rDNA amplification and sequencing. The probiotic potential of strain
      LD1 was assessed by different standard parameters. Cell surface hydrophobicity
      was recorded to be 62% with SAT value <0.007 M. Seventy-eight percent of viable
      count was found after treatment with simulated gastric juice containing pepsin
      (pH 2.0). Bile salt tolerance and bile salt hydrolase activity were also
      demonstrated by strain LD1. The culture supernatant was able to inhibit food
      borne as well as clinical pathogenic microorganisms such as Staphylococcus
      aureus, Salmonella typhimurium, Shigella flexneri, Pseudomonas aeruginosa,
      urogenic Escherichia coli and Vibrio sp. Strain LD1 was found to be sensitive to
      most of the antibiotics used in the study. Since strain has been isolated from
      food source that is most typical of Southern India, it would be safe for further
      consumption in probiotic products.

PMID- 24676725
TI  - Descemet's stripping automated endothelial keratoplasty with anterior chamber
      intraocular lenses: complications and 3-year outcomes.
AB  - PURPOSE: To describe outcomes and complications following Descemet's stripping
      automated endothelial keratoplasty (DSAEK) in eyes with pseudophakic bullous
      keratopathy (BK) while retaining the anterior chamber intraocular lenses (ACIOL).
      METHODS: We included consecutive patients who underwent DSAEK for BK at a single
      tertiary centre from 1 January 2008 to 1 April 2010, from our prospective cohort
      (Singapore Corneal Transplant Study). We compared eyes with BK, which underwent
      DSAEK while retaining ACIOL (n=18), to those with DSAEK alone with the posterior
      chamber intraocular lenses left in place as a comparison group (n=114). Main
      outcome measures were endothelial cell (EC) loss and graft survival. RESULTS: The
      percentage EC loss at 1 year was 31.9+/-21.3% in the DSAEK with ACIOL group
      compared to 24.5+/-21.2% in the DSAEK group (p=0.516); however, this figure was
      significantly greater in the DSAEK with ACIOL group at 3 years compared to the
      DSAEK group (55.3+/-29.2% vs 33.3+/-20.8%; p=0.01 respectively). Graft survival
      was also significantly poorer in the DSAEK ACIOL group compared to the DSAEK
      group over 3 years (log rank p=0.002). CONCLUSIONS: We found that although eyes
      with BK and ACIOL that underwent DSAEK while retaining the ACIOL suffered EC loss
      which was not significantly greater at 1 year, EC loss and graft survival were
      significantly poorer compared to DSAEK controls at 3 years postoperatively.

PMID- 24676726
TI  - Expression of TNF-alpha, OPG, IL-1beta and the presence of the measles virus RNA
      in the stapes of the patients with otosclerosis.
AB  - Persistent measles virus infections play a crucial role in the pathomechanism of
      otosclerosis. The study was undertaken to investigate the role of tumor necrosis
      factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta) and osteoprotegerin (OPG)
      in otosclerotic bone remodeling and to assess the relation of TNF-alpha, OPG and
      IL-1beta expression levels in otosclerotic stape footplates to the occurrence of
      measles virus infection. 61 patients with otosclerosis were treated surgically.
      Thirty-one stapes obtained from cadavers of people, who had died from a sudden
      cause were used as a control group. The presence of measles virus RNA and the
      expression levels of TNF-alpha, IL-1beta and OPG in otosclerotic foci were
      assessed using one-step RT-PCR. The presence of measles virus RNA was noted in
      80.3 % of otosclerotic stapes (49 out of 61) and 9.7 % of normal tissues (3 out
      of 31). Transcript of TNF-alpha, IL-1beta and OPG was detected in 40, 46 and 18
      virus-positive stapes, respectively. The transcript level of TNF-alpha and IL
      1beta was significantly higher in otosclerotic tissues comparing to normal
      tissue. The OPG expression level was significantly lower in otosclerotic tissues
      comparing to controls. The presence of measles virus RNA in the stapes may
      indicate its role in the pathogenesis of otosclerosis. The presence of TNF-alpha
      and IL-1beta mRNA in the virus-positive stapes could be the result of viral
      antigen stimulation and may be a marker of inflammation the otosclerotic focus.
      The lack of OPG mRNA and the presence of TNF-alpha and IL-1beta mRNA in the
      majority of otosclerotic tissues reflect the bone remodeling process occurring in
      the stapes.

PMID- 24676727
TI  - Survivin expression correlates with nodal metastasis in T1-T2 squamous cell
      carcinoma of the tongue.
AB  - In this study, the correlation between neck metastasis and recurrence was
      investigated by studying specimens of tongue squamous cell carcinoma patients
      immunohistochemical with survivin antibodies in the primary biopsy. A
      retrospective review was conducted at the Academic University Hospital. 46
      patients who had squamous cell carcinoma of the tongue, who underwent various
      types of glossectomy and neck dissections between 1991 and 2008, were evaluated.
      The patient's sex, TNM staging, differentiation and recurrence rates were
      analyzed. There were 20 T1 patients and 26 T2 patients; 27 of the patients were
      N0 and 19 had metastatic lymph nodes in the neck. Survivin antibodies were
      applied with streptavidin-biotin method to the sections that were prepared from
      the primary tumor biopsy specimens of the patients. The correlation between neck
      metastasis and recurrence and survivins' immunohistochemical staining was
      analyzed with statistical methods. There were no significant differences between
      the patient's age, sex, tumor's T stage, tumor differentiation and survivin
      staining density. Survivin staining was positive in 15 (79 %) of 19 patients with
      neck metastasis, while it was positive in 16 (59 %) of 27 patients without neck
      metastasis. Eleven (79 %) of the 14 patients who had recurrence and all 6
      patients who had neck recurrence only were stained by survivin. Expression of
      nuclear and cytoplasmic survivin can be a useful marker for predicting cervical
      lymph node metastasis in T1-T2 tumors in tongue SCC.

PMID- 24676728
TI  - Methyloparacoccus murrellii gen. nov., sp. nov., a methanotroph isolated from
      pond water.
AB  - Two novel methanotrophic strains, R-49797(T) and OS501, were isolated from pond
      water in South Africa and Japan, respectively. Strains R-49797(T) and OS501
      shared 99.7% 16S rRNA gene sequence similarity. Cells were Gram-stain-negative,
      non-motile cocci with a diplococcoid tendency and contained type I methanotroph
      intracytoplasmic membranes. The pmoA gene encoding particulate methane
      monooxygenase was present. Soluble methane monoooxygenase (sMMO) activity, the
      mmoX gene encoding sMMO and the nifH gene encoding nitrogenase were not detected.
      Methane and methanol were utilized as sole carbon source. The strains grew
      optimally at 25-33  degrees C (range 20-37  degrees C) and at pH 6.3-6.8 (range
      5.8-9.0). The strains did not support growth in media supplemented with 1% (w/v)
      NaCl. For both strains, the two major fatty acids were C(16 : 1)omega7c and C(16
      : 0) and the DNA G+C content was 65.6 mol%. The isolates belong to the family
      Methylococcaceae of the class Gammaproteobacteria and cluster most closely among
      the genera Methylocaldum, Methylococcus and Methylogaea, with a 16S rRNA gene
      sequence similarity of 94.2% between strain R-49797(T) and its closest related
      type strain (Methylocaldum gracile VKM 14L(T)). Based on the low 16S rRNA gene
      sequence similarities with its nearest phylogenetic neighbouring genera, the
      formation of a separate lineage based on 16S rRNA and pmoA gene phylogenetic
      analysis, and the unique combination of phenotypic characteristics of the two
      isolated strains compared with the genera Methylocaldum, Methylococcus and
      Methylogaea, we propose to classify these strains as representing a novel species
      of a new genus, Methyloparacoccus murrellii gen. nov., sp. nov., within the
      family Methylococcaceae. The type strain of Methyloparacoccus murrellii is R
      49797(T) ( = LMG 27482(T) = JCM 19379(T)).

PMID- 24676729
TI  - Thermotoga profunda sp. nov. and Thermotoga caldifontis sp. nov., anaerobic
      thermophilic bacteria isolated from terrestrial hot springs.
AB  - Two thermophilic, strictly anaerobic, Gram-negative bacteria, designated strains
      AZM34c06(T) and AZM44c09(T), were isolated from terrestrial hot springs in Japan.
      The optimum growth conditions for strain AZM34c06(T) were 60  degrees C, pH 7.4
      and 0% additional NaCl, and those for strain AZM44c09(T) were 70  degrees C, pH
      7.4 and 0% additional NaCl. Complete genome sequencing was performed for both
      strains, revealing genome sizes of 2.19 Mbp (AZM34c06(T)) and 2.01 Mbp
      (AZM44c09(T)). Phylogenetic analyses based on 16S rRNA gene sequences and the
      concatenated predicted amino acid sequences of 33 ribosomal proteins showed that
      both strains belonged to the genus Thermotoga. The closest relatives of strains
      AZM34c06(T) and AZM44c09(T) were the type strains of Thermotoga lettingae (96.0%
      similarity based on the 16S rRNA gene and 84.1% similarity based on ribosomal
      proteins) and Thermotoga hypogea (98.6 and 92.7% similarity), respectively. Using
      blast, the average nucleotide identity was 70.4-70.5% when comparing strain
      AZM34c06(T) and T. lettingae TMO(T) and 76.6% when comparing strain AZM44c09(T)
      and T. hypogea NBRC 106472(T). Both values are far below the 95% threshold value
      for species delineation. In view of these data, we propose the inclusion of the
      two isolates in the genus Thermotoga within two novel species, Thermotoga
      profunda sp. nov. (type strain AZM34c06(T) = NBRC 106115(T) = DSM 23275(T)) and
      Thermotoga caldifontis sp. nov. (type strain AZM44c09(T) = NBRC 106116(T) = DSM
      23272(T)).

PMID- 24676730
TI  - Lactivibrio alcoholicus gen. nov., sp. nov., an anaerobic, mesophilic, lactate-,
      alcohol-, carbohydrate- and amino-acid-degrading bacterium in the phylum
      Synergistetes.
AB  - A mesophilic, obligately anaerobic, lactate-, alcohol-, carbohydrate- and amino
      acid- degrading bacterium, designated strain 7WAY-8-7(T), was isolated from an
      upflow anaerobic sludge blanket reactor treating high-strength organic wastewater
      from isomerized sugar production processes. Cells of strain 7WAY-8-7(T) were
      motile, curved rods (0.7-1.0*5.0-8.0 um). Spore formation was not observed. The
      strain grew optimally at 37  degrees C (range for growth was 25-40  degrees C)
      and pH 7.0 (pH 6.0-7.5), and could grow fermentatively on yeast extract, glucose,
      ribose, xylose, malate, tryptone, pyruvate, fumarate, Casamino acids, serine and
      cysteine. The main end-products of glucose fermentation were acetate and
      hydrogen. In co-culture with the hydrogenotrophic methanogen Methanospirillum
      hungatei DSM 864(T), strain 7WAY-8-7(T) could utilize lactate, glycerol, ethanol,
      1-propanol, 1-butanol, L-glutamate, alanine, leucine, isoleucine, valine,
      histidine, asparagine, glutamine, arginine, lysine, threonine, 2-oxoglutarate,
      aspartate and methionine. A Stickland reaction was not observed with some pairs
      of amino acids. Yeast extract was required for growth. Nitrate, sulfate,
      thiosulfate, elemental sulfur, sulfite and Fe (III) were not used as terminal
      electron acceptors. The G+C content of the genomic DNA was 61.4 mol%. 16S rRNA
      gene sequence analysis revealed that the isolate belongs to the uncultured
      environmental clone clade (called 'PD-UASB-13' in the Greengenes database) in the
      bacterial phylum Synergistetes, showing less than 90% sequence similarity with
      closely related described species such as Aminivibrio pyruvatiphilus and
      Aminobacterium colombiense (89.7% and 88.7%, respectively). The major cellular
      fatty acids were iso-C(13 : 0), iso-C(15 : 0), anteiso-C(15 : 0), C(18 : 1), C(19
      : 1), C(20 : 1) and C(21 : 1). A novel genus and species, Lactivibrio alcoholicus
      gen. nov., sp. nov. is proposed to accommodate strain 7WAY-8-7(T) ( = JCM
      17151(T) = DSM 24196(T) = CGMCC 1.5159(T)).

PMID- 24676731
TI  - Molecular signatures for members of the genus Dehalococcoides and the class
      Dehalococcoidia.
AB  - The bacteria belonging to the class Dehalococcoidia, due to their ability to
      dehalogenate chlorinated compounds, are of much interest for bioremediation of
      contaminated sites. We report here comparative analyses on different
      genes/proteins from the genomes of members of the class Dehalococcoidia. These
      studies have identified numerous novel molecular markers in the forms of
      conserved signature indels (CSIs) in broadly distributed proteins and conserved
      signature genes/proteins (CSPs), which are uniquely found in members of the class
      Dehalococcoidia, but except for an isolated exception, they are not found in
      other sequenced bacterial genomes. Of these molecular markers, nine CSIs in
      divergent proteins and 19 CSPs are specific for members of the genera
      Dehalococcoides and Dehalogenimonas, providing potential molecular markers for
      the bacterial class Dehalococcoidia. Additionally, four CSIs in divergent
      proteins and 28 CSPs are only found in all members of the genus Dehalococcoides
      for which genome sequences are available, but they are absent in Dehalogenimonas
      lykanthroporepellens and in other bacteria. The gene sequences of several of
      these CSPs exhibiting specificity for the genus Dehalococcoides or the class
      Dehalococcoidia are highly conserved and PCR primers based upon them provide a
      novel means for identification of other related bacteria. Two other CSIs
      identified in this study in the SecD and aspartate carbomyltransferase proteins
      weakly support an affiliation of the class Dehalococcoidia with the other members
      of the phylum Chloroflexi. 

PMID- 24676734
TI  - A multiple time step scheme for multiresolved models of macromolecules.
AB  - In hybrid particle models where coarse-grained beads and atoms are used
      simultaneously, two clearly separate time scales are mixed. If such models are
      used in molecular dynamics simulations, a multiple time step (MTS) scheme can
      therefore be used. In this manuscript, we propose a simple MTS algorithm which
      approximates for a specific number of integration steps the slow coarse-grained
      bead-bead interactions with a Taylor series approximation while the atom-atom
      ones are integrated every time step. The procedure is applied to a previously
      developed hybrid model of a melt of atactic polystyrene (di Pasquale, Marchisio,
      and Carbone, J. Chem. Phys. 2012, 137, 164111). The results show that structure,
      local dynamics, and free diffusion of the model are not altered by the
      application of the integration scheme which can confidently be used to simulate
      multiresolved models of polymer melts.

PMID- 24676733
TI  - Thermoflexus hugenholtzii gen. nov., sp. nov., a thermophilic, microaerophilic,
      filamentous bacterium representing a novel class in the Chloroflexi, Thermoflexia
      classis nov., and description of Thermoflexaceae fam. nov. and Thermoflexales
      ord. nov.
AB  - A thermophilic, filamentous, heterotrophic bacterium, designated strain JAD2(T),
      a member of an as-yet uncultivated lineage that is present and sometimes abundant
      in some hot springs worldwide, was isolated from sediment of Great Boiling Spring
      in Nevada, USA. Cells had a mean diameter of 0.3 um and length of 4.0 um, and
      formed filaments that typically ranged in length from 20 to 200 um. Filaments
      were negative for the Gram stain reaction, spores were not formed and motility
      was not observed. The optimum temperature for growth was 72.5-75  degrees C, with
      a range of 67.5-75  degrees C, and the optimum pH for growth was 6.75, with a
      range of pH 6.5-7.75. Peptone, tryptone or yeast extract were able to support
      growth when supplemented with vitamins, but no growth was observed using a
      variety of defined organic substrates. Strain JAD2(T) was microaerophilic and
      facultatively anaerobic, with optimal growth at 1% (v/v) O2 and an upper limit of
      8% O2. The major cellular fatty acids (>5%) were C(16 : 0), C(19 : 0), C(18 : 0),
      C(20 : 0) and C(19 : 1). The genomic DNA G+C content was 69.3 mol%. Phylogenetic
      and phylogenomic analyses using sequences of the 16S rRNA gene and other
      conserved genes placed JAD2(T) within the phylum Chloroflexi, but not within any
      existing class in this phylum. These results indicate that strain JAD2(T) is the
      first cultivated representative of a novel lineage within the phylum Chloroflexi,
      for which we propose the name Thermoflexus hugenholtzii gen. nov., sp. nov.,
      within Thermoflexia classis nov., Thermoflexales ord. nov. and Thermoflexaceae
      fam. nov. The type strain of Thermoflexus hugenholtzii is JAD2(T) ( = JCM
      19131(T) = CCTCC AB-2014030(T)).

PMID- 24676732
TI  - Hymenobacter arcticus sp. nov., isolated from glacial till.
AB  - A novel, red-pink-pigmented strain, designated R2-4(T), was isolated from a till
      sample near Ny-Alesund, Svalbard Archipelago, Norway. Cells were aerobic, Gram
      stain-negative and rod-shaped. Growth occurred at 4-30  degrees C (optimum, 20-22
      degrees C), at pH 6.0-9.0 (optimum, pH 7.0) and with 0-1% NaCl added to R2A
      agar. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      strain R2-4(T) belonged to the genus Hymenobacter. 16S rRNA gene sequence
      similarity between strain R2-4(T) and the type strains of related species of the
      genus ranged from 94.51 to 96.05%. Strain R2-4(T) contained iso-C(15 : 0),
      anteiso-C(15 : 0), summed feature 3 (C(16 : 1)omega6c and/or C(16 : 1)omega7c),
      summed feature 4 (C(17 : 1) anteiso B and/or iso I) and C(16 : 1)omega5c as the
      major cellular fatty acids, MK-7 as the major respiratory quinone, and
      phosphatidylethanolamine, unknown aminophospholipids, unknown aminolipids and
      unknown lipids as the main polar lipids. The polyamine was sym-homospermidine.
      The DNA G+C content of strain R2-4(T) was 61.6 mol%. On the basis of
      phylogenetic, physiological and chemotaxonomic data, strain R2-4(T) is considered
      to represent a novel species of the genus Hymenobacter, for which the name
      Hymenobacter arcticus sp. nov. is proposed. The type strain is R2-4(T) ( = CCTCC
      AB 2012104(T) = KACC 16881(T)).

PMID- 24676735
TI  - Lymph node size as a predictor of lymphatic staging in colonic cancer.
AB  - BACKGROUND: In colonic cancer, the number of harvested lymph nodes is associated
      with prognosis. The aim of this study was to determine the contribution of small
      lymph nodes to pathological staging, and to analyse the hypothesis that node size
      is a confounder in the relationship between prognosis and nodal harvest. METHODS:
      Nodal harvest and size were analysed in patients who underwent elective surgery
      for colonic cancer. Visible and palpable nodes were harvested without fat
      clearance techniques, and conventional histology was performed. RESULTS:
      Metastases were found in 99 of 2043 measured lymph nodes in 150 patients. Lymph
      nodes smaller than 3 mm were positive in 8.0 per cent of patients (12 of 150),
      but were the sole reason for upstaging in only 1.3 per cent (2 of 150). No
      metastases were found among 95 nodes of 1 mm or less. Metastatic nodes were
      larger than those without metastasis (median (i.q.r.) 5.0 (3.2-7.0) versus 3.8
      (2.4-5.2) mm; P < 0.001), but a receiver operating characteristic (ROC) curve did
      not identify a relevant cut-off point to predict metastatic involvement. A hazard
      ratio of 0.71 (95 per cent confidence interval 0.50 to 1.01) was suggestive of an
      association between disease recurrence and increased node size, although not
      significant (P = 0.056). In patients with N0 disease, there was a correlation
      between node size and harvest (Pearson's correlation 0.317, P = 0.002), and a
      nodal yield of at least 12 was associated with a larger median node size (4.3
      (3.3-5.0) versus 3.4 (2.7-4.0) mm; P = 0.015). CONCLUSION: The contribution of
      lymph nodes smaller than 3 mm to nodal staging is limited. Increased node size is
      associated with increased nodal yield, and could be a confounder in the
      relationship between prognosis and nodal harvest in patients with N0 disease.

PMID- 24676737
TI  - Spontaneous thrombosis of developmental venous anomaly (DVA) with venous infarct
      and acute cerebellar ataxia.
AB  - Developmental venous anomaly (DVA), formally known as venous angioma, is a
      congenital anatomic variant of the venous drainage of the brain. Although they
      typically have a benign clinical course and a low symptomatic rate, thrombosis of
      a drainage vein may occur, leading to potentially debilitating complications. We
      report a unique case of spontaneous thrombosis of a posterior fossa developmental
      venous anomaly with cerebellar infarct in a 61-year-old man who presented with
      acute onset cerebellar ataxia. DVA thrombosis was well-depicted on CT and MR
      studies. Patient was put on anticoagulant therapy and complete recanalization was
      seen on follow-up imaging. 

PMID- 24676738
TI  - Peritoneal dialysis-associated peritonitis: unfinished business.

PMID- 24676739
TI  - Genetic variants and risk of chronic kidney disease.

PMID- 24676736
TI  - Dual-energy computed tomography (DECT) in emergency radiology: basic principles,
      techniques, and limitations.
AB  - Recent advances in computed tomography (CT) technology allow for acquisition of
      two CT datasets with different X-ray spectra. There are different dual-energy
      computed tomography (DECT) technical approaches such as: the dual-source CT, the
      fast kilovoltage-switching method, and the sandwich detectors technique. There
      are various postprocessing algorithms that are available to provide clinically
      relevant spectral information. There are several clinical applications of DECT
      that are easily accessible in the emergency setting. In this review article, we
      aim to provide the emergency radiologist with a discussion on how this new
      technology works and how some of its applications can be useful in the emergency
      room setting. 

PMID- 24676740
TI  - Peritonitis rates of the past thirty years: from improvement to stagnation.

PMID- 24676741
TI  - Vancomycin: the tale of the vanquisher and the pyrrhic victory.
AB  - Vancomycin has been the antibiotic of choice in the treatment of methicillin
      resistant Staphylococcus aureus infections for decades. But relatively recently,
      vancomycin-intermediate-susceptible S. aureus (VISA) have been reported.
      Phenotypically, VISA are characterized by thicker cell walls, requiring higher
      concentrations of vancomycin for inhibition of bacterial cell growth. Vancomycin
      intermediate-susceptible S. aureus represent just the tip of the iceberg of an
      insidious loss of vancomycin susceptibility in staphylococci. Increasing
      proportions of S. aureus isolates have higher minimum inhibitory concentrations
      that are still within the officially susceptible range, a characteristic that is
      associated with treatment failure. The most important risk factor for decreased
      vancomycin susceptibility is in vivo selection pressure. To prevent the
      development of VISA, prolonged or inappropriate use of vancomycin and suboptimal
      vancomycin levels should be avoided. Trough serum vancomycin concentrations of 15
      - 20 mg/L for intermittent dosing and plateau serum vancomycin concentrations of
      20 - 25 mg/L for continuous infusions are therefore currently recommended. The
      widespread clinical application of these intensive dosing regimens has resulted
      in an increasing awareness of vancomycin-induced nephrotoxicity, which is
      especially relevant in patients whose renal function is already compromised. This
      narrow therapeutic-toxic window reinforces the use of rigorous dosing protocols.
      In hemodialysis, the use of a vancomycin dose calculator permits achievement of
      target concentrations in most patients. In peritoneal dialysis (PD), intermittent
      vancomycin dosing regimens often lead to low end-of-dwell concentrations. On the
      other hand, a continuous vancomycin dosing regimen after a loading dose offers
      the desired combination of high local levels without toxic systemic levels. 

PMID- 24676742
TI  - Cephazolin and gentamicin are stable in lactate-buffered fresenius peritoneal
      dialysate for seven days at room temperature.

PMID- 24676743
TI  - A high serum vancomycin level is associated with lower relapse rates in coagulase
      negative staphylococcal peritonitis.

PMID- 24676745
TI  - Risk factors that determine removal of the catheter in bacterial peritonitis in
      peritoneal dialysis.

PMID- 24676744
TI  - Successful treatment of vancomycin-resistant enterococcus peritonitis using
      linezolid without catheter removal in a peritoneal dialysis patient.

PMID- 24676746
TI  - Crystallization in transfer set before continuous ambulatory peritoneal dialysis
      initiation-three case reports.

PMID- 24676748
TI  - Solvent screening methodology for in situ ABE extractive fermentation.
AB  - Solvent screening for in situ liquid extraction of products from acetone-butanol
      ethanol (ABE) fermentation was carried out, taking into account biological
      parameters (biocompatibility, bioavailability, and product yield) and extraction
      performance (partition coefficient and selectivity) determined in real
      fermentation broth. On the basis of different solvent characteristics obtained
      from literature, 16 compounds from different chemical families were selected and
      experimentally evaluated for their extraction capabilities in a real ABE
      fermentation broth system. From these compounds, nine potential solvents were
      also tested for their biocompatibility towards Clostridium acetobutylicum.
      Moreover, bioavailability and differences in substrate consumption and total n
      butanol production with respect to solvent-free fermentations were quantified for
      each biocompatible solvent. Product yield was enhanced in the presence of organic
      solvents having higher affinity for butanol and butyric acid. Applying this
      methodology, it was found that the Guerbet alcohol 2-butyl-1-octanol presented
      the best extracting characteristics (the highest partition coefficient (6.76) and
      the third highest selectivity (644)), the highest butanol yield (27.4 %), and
      maintained biocompatibility with C. acetobutylicum. 

PMID- 24676747
TI  - Peritonitis caused by veillonella species and Eggerthella lenta in peritoneal
      dialysis.

PMID- 24676749
TI  - Effects of mutation at position 285 of Ralstonia pickettii T1 poly[(R)-3
      hydroxybutyrate] depolymerase on its activities.
AB  - Asn at position 285 (N285) in the catalytic domain of poly[(R)-3-hydroxybutyrate]
      (PHB) depolymerase from Ralstonia pickettii T1 most likely participates in the
      cleavage of ester bonds as revealed by our previous evolutionary engineering
      study using the error-prone polymerase chain reaction (PCR) method. To
      exhaustively examine the effects of mutations at that position, we conducted site
      directed saturation mutagenesis at that position and the resultant mutant enzymes
      (N285X) were evaluated in p-nitrophenyl ester (pNPCn) hydrolysis and PHB
      degradation. Kinetic studies demonstrated that the PHB-degrading activities of
      N285X were reciprocally related to their pNPCn-hydrolyzing activities, with the
      exception of N285A and N285G, and that His residue could functionally substitute
      for Asn285 on PHB degradation. 

PMID- 24676750
TI  - Degradation of atrazine by Frankia alni ACN14a: gene regulation, dealkylation,
      and dechlorination.
AB  - Atrazine is transformed to N-isopropylammelide through hydroxyatrazine as an
      intermediate as indicated by high-performance liquid chromatography/mass
      spectroscopy in culture filtrates of Frankia alni ACN14a and Frankia sp. EuI1c.
      Both Frankia strains have the ability to degrade atrazine via dechlorination and
      dealkylation and, subsequently, may be using it as a nitrogen and carbon source
      as detected here by increasing their growth patterns. Bioinformatic analysis of
      the Frankia genomes revealed that a potential gene cluster involved in atrazine
      decomposition contains three genes, namely, trzN (FRAAL1474 and FraEuI1c_5874),
      atzB (FRAAL1473 and FraEuI1c_5875), and atzR (FRAAL1471). The relative messenger
      RNA gene expression of the former genes was examined by qRT-PCR. The LysR-type
      transcriptional regulator atzR (FRAAL1471), which is expected to control the
      cluster expression, showed a 13-fold increase in the expression level under
      atrazine stress. Moreover, the putative adenosine aminohydrolase 3 atzB
      (FRAAL1473), which is expected to dealkylate the N-ethyl group of atrazine,
      showed also an increased expression by factor 16 with increased exposure.
      Eventually, the trzN (FRAAL1474) gene, which is predicted to encode a putative
      amidohydrolase catalyzing atrazine dechlorination, exhibited 31-fold increased
      expression. To our best knowledge, this is the first report about adenosine
      aminohydrolase 3 function in the dealkylation of the N-ethyl group from atrazine.

PMID- 24676751
TI  - Pore-forming toxins from pathogenic amoebae.
AB  - Some amoeboid protozoans are facultative or obligate parasites in humans and bear
      an enormous cytotoxic potential that can result in severe destruction of host
      tissues and fatal diseases. Pathogenic amoebae produce soluble pore-forming
      polypeptides that bind to prokaryotic and eukaryotic target cell membranes and
      generate pores upon insertion and oligomerization. This review summerizes the
      current knowledge of such small protein toxins from amoebae, compares them with
      related proteins from other species, focuses on their three-dimensional
      structures, and gives insights into divergent activation mechanisms. The
      potential use of pore-forming toxins in biotechnology will be briefly outlined.

PMID- 24676752
TI  - Permutation tests for centre effect on survival endpoints with application in an
      acute myeloid leukaemia multicentre study.
AB  - When analysing multicentre data, it may be of interest to test whether the
      distribution of the endpoint varies among centres. In a mixed-effect model,
      testing for such a centre effect consists in testing to zero a random centre
      effect variance component. It has been shown that the usual asymptotic chi(2)
      distribution of the likelihood ratio and score statistics under the null does not
      necessarily hold. In the case of censored data, mixed-effects Cox models have
      been used to account for random effects, but few works have concentrated on
      testing to zero the variance component of the random effects. We propose a
      permutation test, using random permutation of the cluster indices, to test for a
      centre effect in multilevel censored data. Results from a simulation study
      indicate that the permutation tests have correct type I error rates, contrary to
      standard likelihood ratio tests, and are more powerful. The proposed tests are
      illustrated using data of a multicentre clinical trial of induction therapy in
      acute myeloid leukaemia patients.

PMID- 24676753
TI  - Prognosis Related to Metastatic Burden Measured by 18F-Fluorocholine PET/CT in
      Castration-Resistant Prostate Cancer.
AB  - This study investigated the prognostic significance of metabolically active tumor
      volume (MATV) measurements applied to (18)F-fluorocholine PET/CT in castration
      resistant prostate cancer (CRPC). METHODS: (18)F-fluorocholine PET/CT imaging was
      performed on 30 patients with CRPC. Metastatic disease was quantified on the
      basis of maximum standardized uptake value (SUV(max)), MATV, and total lesion
      activity (TLA = MATV * mean standardized uptake value). Tumor burden indices
      derived from whole-body summation of PET tumor volume measurements (i.e., net
      MATV and net TLA) were evaluated as variables in Cox regression and Kaplan-Meier
      survival analyses. RESULTS: Net MATV ranged from 0.12 cm(3) to 1,543.9 cm(3)
      (median, 52.6 cm(3)). Net TLA ranged from 0.40 to 6,688.7 g (median, 225.1 g).
      Prostate-specific antigen level at the time of PET correlated significantly with
      net MATV (Pearson r = 0.65, P = 0.0001) and net TLA (r = 0.60, P = 0.0005) but
      not highest lesional SUV(max) of each scan. Survivors were followed for a median
      23 mo (range, 6-38 mo). On Cox regression analyses, overall survival had a
      significant association with net MATV (P = 0.0068), net TLA (P = 0.0072), and
      highest lesion SUV(max) (P = 0.0173) and a borderline association with prostate
      specific antigen level (P = 0.0458). Only net MATV and net TLA remained
      significant in univariate-adjusted survival analyses. Kaplan-Meier analysis
      demonstrated significant differences in survival between groups stratified by
      median net MATV (log-rank P = 0.0371), net TLA (log-rank P = 0.0371), and highest
      lesion SUV(max) (log-rank P = 0.0223). CONCLUSION: Metastatic prostate cancer
      detected by (18)F-fluorocholine PET/CT can be quantified on the basis of
      volumetric measurements of tumor metabolic activity. The prognostic value of
      (18)F-fluorocholine PET/CT may stem from this capacity to assess whole-body tumor
      burden. With further clinical validation, (18)F-fluorocholine PET-based indices
      of global disease activity and mortality risk could prove useful in patient
      individualized treatment of CRPC.

PMID- 24676754
TI  - 11C-acetate PET/CT for metabolic characterization of multiple myeloma: a
      comparative study with 18F-FDG PET/CT.
AB  - We prospectively compared (11)C-acetate with (18)F-FDG in a PET/CT evaluation of
      multiple myeloma (MM), specifically on diagnostic accuracy, identification of
      high-risk patients, and monitoring of treatment response. METHODS: Dual-tracer
      PET/CT was performed on 35 pathologically and clinically confirmed and untreated
      patients (26 with symptomatic MM, 5 with smoldering MM, and 4 with monoclonal
      gammopathy of unknown significance) and 20 individuals with normal marrow.
      RESULTS: (11)C-acetate showed significant incremental value over (18)F-FDG (84.6%
      vs. 57.7%) for positively identifying patients with diffuse and focal symptomatic
      MM, and was negative in patients with indolent smoldering MM and monoclonal
      gammopathy of unknown significance. Three functional parameters-number of (11)C
      acetate-avid and (18)F-FDG-avid focal bone lesions and (11)C-acetate general
      marrow activity-strongly correlated with beta-2-microglobulin as surrogate
      imaging markers of tumor burden. After induction chemotherapy, the metabolic
      change in (11)C-acetate general marrow activity correlated with clinical
      response. CONCLUSION: Metabolic characterization of MM in diagnosis, risk
      stratification, and treatment monitoring can be done more accurately by assessing
      lipid metabolism with (11)C-acetate than by assessing glucose metabolism with
      (18)F-FDG.

PMID- 24676755
TI  - Postchemotherapy and tumor-selective targeting with the La-specific DAB4
      monoclonal antibody relates to apoptotic cell clearance.
AB  - Early identification of tumor responses to treatment is crucial for devising more
      effective and safer cancer treatments. No widely applicable, noninvasive method
      currently exists for specifically detecting tumor cell death after cytotoxic
      treatment and thus for predicting treatment outcomes. METHODS: We have further
      characterized the targeting of the murine monoclonal antibody DAB4 specifically
      to dead tumor cells in vitro, in vivo, and in clinical samples. We found that
      sustained DAB4 binding to treated cells was closely associated with markers of
      intrinsic apoptosis and DNA double-strand break formation. In a competition
      binding assay, DAB4 bound EL4 murine thymic lymphoma cells in preference to the
      normal counterpart of murine thymocytes. Defective in vivo clearance of apoptotic
      cells augmented in vivo accumulation of DAB4 in tumors particularly after
      chemotherapy but was unchanged in normal tissues. Tumor targeting of DAB4 was
      selective for syngeneic murine tumors and for human tumor xenografts of prostate
      cancer (PC-3) and pancreatic cancer (Panc-1) before and more so after
      chemotherapy. Furthermore, DAB4 was shown to bind to dead primary acute
      lymphoblastic leukemic blasts cultured with cytotoxic drugs and dead epithelial
      cancer cells isolated from peripheral blood of small cell lung carcinoma patients
      given chemotherapy. CONCLUSION: Collectively, these results further demonstrate
      the selectivity of DAB4 for chemotherapy-induced dead tumor cells. This
      postchemotherapy selectivity is related to a relative increase in the
      availability of DAB4-binding targets in tumor tissue rather than in normal
      tissues. The in vitro findings were translated in vivo to human xenograft models
      and to ex vivo analyses of clinical samples, providing further evidence of the
      potential of DAB4 as a marker of tumor cell death after DNA-damaging cytotoxic
      treatment that could be harnessed as a predictive marker of treatment responses.

PMID- 24676756
TI  - 11C-cetrozole: an improved C-11C-methylated PET probe for aromatase imaging in
      the brain.
AB  - Aromatase (an enzyme that converts androgens to estrogens) in the brain is
      involved in neuroprotection, synaptic plasticity, and regulation of sexual and
      emotional behaviors. To investigate the physiologic and pathologic importance of
      aromatase in the brain, including in humans, we here report the development of a
      novel PET probe for aromatase, (11)C-cetrozole, which allows noninvasive
      quantification of aromatase expression. METHODS: (11)C-cetrozole was synthesized
      by the C-(11)C-methylation method developed by our group. In vitro
      autoradiography of frozen sections and a binding study with rat brain homogenates
      were conducted to demonstrate the specific binding and the dissociation constant.
      PET studies with anesthetized rhesus monkeys were performed to analyze the
      dynamics in the brain. RESULTS: In vitro and in vivo studies using (11)C
      cetrozole showed its superiority in brain aromatase imaging in terms of
      specificity and selectivity, compared with previously developed (11)C-vorozole.
      PET studies showed that (11)C-cetrozole had a higher signal-to-noise ratio,
      providing a sharper image than (11)C-vorozole, because the radioactive metabolite
      of (11)C-vorozole was taken up into the brain. High specific binding of (11)C
      cetrozole was observed in the amygdala and hypothalamus, and we also noted
      binding in the nucleus accumbens of rhesus monkeys for the first time.
      CONCLUSION: These results suggest that PET imaging with newly developed (11)C
      cetrozole is suitable for quantifying the expression of brain aromatase in vivo,
      possibly providing critical information regarding the functional roles of
      aromatase in human neurologic and emotional disorders.

PMID- 24676757
TI  - Plasma growth arrest-specific protein 6 levels in premenopausal and
      postmenopausal women: the role of endogenous estrogen.
AB  - Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein that interacts
      with receptor tyrosine kinases of the Tyro-3, AXL, Mer (TAM) family. The Gas6/TAM
      system contributes to the regulation of cell survival and proliferation, cell
      adhesion and migration, and inflammatory cytokines release. Plasma Gas6 plays an
      important role in the inflammatory process, and is involved in diverse human
      diseases. Few studies have investigated gender-specific variations in plasma Gas6
      concentration. Hence, the aim of this study was to determine whether plasma Gas6
      levels are associated with sex hormones in premenopausal and postmenopausal
      women. A total of 103 premenopausal and 135 postmenopausal women were recruited.
      Plasma Gas6 concentration, estradiol (E2), and sex hormone-binding globulin were
      assayed. The free estrogen index (FEI) was calculated. The results showed
      significantly lower Gas6 levels in the postmenopausal compared to the
      premenopausal women (P < 0.005). Plasma Gas6 levels were positively correlated
      with E2 levels in the pre- and postmenopausal women (r = 0.359, P < 0.001 and r =
      0.261, P = 0.002, respectively). Gas6 levels were also correlated with FEI in the
      pre- and postmenopausal women (r = 0.234, P = 0.017 and r = 0.188, P = 0.029,
      respectively). After adjusting for confounders, the correlations still remained
      significant. In multiple stepwise regression analysis, only E2 in premenopausal
      and both age and E2 in postmenopausal women were independently correlated with
      the plasma Gas6 levels (all P < 0.001). These results suggest that plasma Gas6 is
      associated with sex hormones in both pre- and postmenopausal women, indicating a
      potential role of sex hormones in the Gas6/TAM system.

PMID- 24676758
TI  - Vitamin D status is related to intramyocellular lipid in older adults.
AB  - Vitamin D and intramyocellular lipid (IMCL) both affect muscle function, but the
      relationship between vitamin D status and IMCL has not been established. To
      assess the relationship between vitamin D [measured as 25-hydroxy-vitamin-D
      (25(OH)D)] and IMCL, 20 community-dwelling adults between the ages of 65 and 85
      were recruited. Serum 25(OH)D, and gastrocnemius IMCL and extramyocellular lipid
      (EMCL) were measured with magnetic resonance spectroscopy and fat ratio
      segmentation. A lifestyle questionnaire assessed physical activity. Muscle
      strength (1-repetition maximum) and physical function tests (timed up and go,
      timed sit to stand, four square step test, and gait speed) were also performed.
      Mean 25(OH)D was 37.9 +/- 13.1 ng/mL with a range of 19-68 ng/mL. Soleus and
      gastrocnemius IMCL to water ratio was 1.04 +/- 0.43 and 0.53 +/- 0.22,
      respectively, but only gastrocnemius IMCL was correlated with 25(OH)D (R (2) =
      0.39; p = 0.02). This relationship was independent of body mass index (p > 0.14),
      physical activity level (p > 0.08), and sex (p > 0.13). 25(OH)D did not correlate
      with EMCL (R (2) = 0.007; p = 0.78). The four square step test was the only
      performance or strength test correlated with 25(OH)D (R (2) = 0.26; p = 0.023).
      Muscle strength and physical function measures were not correlated with IMCL or
      EMCL. These data suggest that vitamin D status may influence gastrocnemius IMCL
      content independent of body mass and physical activity. Future studies should
      consider exploring whether vitamin D has an independent role in affecting muscle
      lipid metabolism and function.

PMID- 24676759
TI  - Insulin resistance is associated with the development of albuminuria in Korean
      subjects without diabetes.
AB  - Previous studies have shown that insulin resistance is associated with the
      development of albuminuria. However, most studies are done on a background of
      diabetes or metabolic syndrome and there is little data from general population.
      The aim of this study is to define the effect of insulin resistance on the
      development of albuminuria in healthy individuals without diabetes. We analyzed
      60,047 participants without baseline diabetes or chronic kidney disease, who
      underwent at least two health maintenance visits at a 2-year interval between
      2002 and 2009 at a tertiary hospital in Korea. We measured the incidence of
      albuminuria at the second examination and calculated the odds ratio for the
      development of albuminuria according to the quintile of the homeostasis model
      assessment of insulin resistance (HOMA-IR). After 2 years, 880 cases of incident
      albuminuria were observed. The cumulative incidences of albuminuria were 1.08,
      1.50, 1.35, 1.47, and 1.92% for the 1st to 5th quintiles of HOMA-IR. On
      multivariate logistic analysis, the odds ratios for incident albuminuria compared
      to those in the 1st quintile were 1.38 (95% CI 1.10-1.73; P=0.006), 1.23 (95% CI
      0.97-1.55; P=0.087), 1.32 (95% CI 1.04-1.67; P=0.020), and 1.66 (95% CI 1.31
      2.09; P<0.001) in the 2nd, 3rd, 4th, and 5th quintiles, respectively. A high
      level of insulin resistance assessed with HOMA-IR was associated with the
      development of albuminuria in relatively healthy subjects without diabetes.
      Further research is needed to verify the role of insulin resistance in the
      development of albuminuria and renal injury.

PMID- 24676760
TI  - Evaluation of left ventricle functions by tissue Doppler, strain, and strain rate
      echocardiography in patients with primary hyperparathyroidism.
AB  - Cardiovascular morbidity and mortality are increased in patients with primary
      hyperparathyroidism (PHPT). We aimed to evaluate left ventricle systolic and
      diastolic functions with tissue Doppler imaging (TDI) and strain and strain rate
      echocardiography in patients with PHPT. Thirty-one patients with PHPT and 29
      healthy controls were evaluated with conventional and pulse Doppler
      echocardiography, TDI and strain and strain rate echocardiography. Myocardial
      performance index (MPI) was calculated. Strain and peak systolic strain rate in
      mid and basal segments of lateral, anterior, inferior, and septal walls of left
      ventricle were determined. TDI showed similar late diastolic myocardial peak
      velocity in two groups. Peak systolic mitral annular velocity, early diastolic
      myocardial peak velocity, and ratio of early to late diastolic myocardial peak
      velocity were lower in PHPT patients (p = 0.01, p < 0.001 and p < 0.001,
      respectively). MPI calculated by TDI was 0.53 +/- 0.15 in PHPT group and 0.44 +/-
      0.09 in control group (p = 0.013). Strain values were lower in mid and basal
      segments of septum, lateral and anterior walls, and basal segment of inferior
      wall in PHPT patients. Mean systolic strain was -20.88 +/- 2.30 and -24.25 +/-
      2.13 in PHPT patients and control group, respectively (p < 0.001). Mean strain
      rate was lower in PHPT patients compared to control group (-1.38 +/- 0.19 vs 
      1.57 +/- 0.25) (p = 0.002). Patients with PHPT, but no cardiac symptoms or
      documented cardiovascular disease, have subclinical systolic and diastolic
      myocardial dysfunction. Evaluation of these patients with TDI and S and Sr
      echocardiography in addition to conventional echocardiography might be valuable
      to detect subclinical cardiac involvement.

PMID- 24676761
TI  - Castanea spp. buds as a phytochemical source for herbal preparations: botanical
      fingerprint for nutraceutical identification and functional food standardisation.
AB  - BACKGROUND: Many plant species may be used for the production of herbal
      preparations containing phytochemicals with significant antioxidant and anti
      inflammatory capacities and health benefits: Castanea spp. is among the most
      commonly used herbal medicines. The aim of this research was to perform an
      analytical study of chestnut bud preparations, in order to identify and quantify
      the main bioactive compounds, and to obtain a specific chemical fingerprint to
      evaluate the single class contribution to the herbal preparation phytocomplex.
      The analyses were performed using a high-performance liquid chromatograph coupled
      to a diode array detector. RESULTS: Castanea spp. was identified as a rich source
      of anti-inflammatory and antioxidant compounds: the observed analytical
      fingerprint demonstrated that these bud preparations represent a rich source of
      bioactive compounds (104.77 +/- 1.14 g kg(-1) FW) in relation to different
      genotypes, specific sampling sites and several phenological stages. CONCLUSION:
      This study showed that the observed analytical fingerprint can be considered an
      important tool for assessing the chemical composition and bioactivities of the
      chestnut-derived products, considering the Castanea genus as a new source of
      natural health-promoting compounds. This study allowed the development of an
      effective tool for quality control by fingerprinting the bud preparation in order
      to develop a new generation of standardised preparations.

PMID- 24676763
TI  - Probiotic Potential of Pediococcus pentosaceus CRAG3: A New Isolate from
      Fermented Cucumber.
AB  - A novel strain of lactic acid bacterium isolated from fermented cucumber was
      selected due to its high glucansucrase activity. It was identified on the basis
      of 16S rRNA sequence analysis as Pediococcus pentosaceus CRAG3 (GenBank accession
      number JX679020). The isolate was round shaped, Gram positive, and catalase
      negative displaying typical features of lactic acid bacterium. It produced 145 +/
      3.27 mg lactic acid per ml of cell-free supernatant. It showed ability to
      ferment carbohydrates such as sucrose, dextrose, and arabinose; showed resistance
      to antibiotics such as ciprofloxacin, kanamycin, vancomycin; displayed acid
      production in triple sugar iron agar test and non-motile nature. Interestingly,
      the isolate also displayed potential probiotic properties such as hydrophobicity,
      autoaggregation, coaggregation, and in vitro cell adhesion ability. It exhibited
      resistance against lysozyme and simulated gastric juice at pH 3.0 with 75 and 58%
      survival, respectively. It also showed tolerance toward 0.3%, w/v bile salts with
      73% survival and ability to deconjugate bile salts. The isolate exhibited
      antibacterial activity and ability to utilize prebiotics such as inulin and
      raffinose. These results indicate both probiotic property and glucansucrase
      producing ability of P. pentosaceus CRAG3.

PMID- 24676762
TI  - In vitro comparison of the effects of probiotic, commensal and pathogenic strains
      on macrophage polarization.
AB  - Macrophages are important with respect to both innate and adaptive immune
      responses and are known to differentiate into pro-inflammatory M1- or anti
      inflammatory M2-phenotypes following activation. In order to study how different
      bacteria affect macrophage polarization, we exposed murine RAW 264.7 macrophages
      to sixteen different strains representing probiotic strains, pathogens,
      commensals and strains of food origin. Increased inducible nitric oxide synthase
      (iNOS) or arginase-1 gene expression indicates M1 or M2 polarization,
      respectively, and was quantified by qRT-PCR. Strains of Escherichia and
      Salmonella elevated iNOS expression more so than strains of Enterococcus,
      Lactobacillus and Lactococcus, indicating that Gram-negative strains are more
      potent M1 inducers. However, strain-specific responses were observed. For
      instance, Escherichia coli Nissle 1917 was a poor inducer of iNOS gene expression
      compared to the other E. coli strains, while Enterococcus faecalis Symbioflor-1
      was more potent in this respect compared to all the eleven Gram-positive strains
      tested. Macrophage polarization was further characterized by quantifying secreted
      pro- and anti-inflammatory cytokines. Exposure to the pathogen E. coli 042
      produced a cytokine profile indicating M1 differentiation, which is in accordance
      with the PCR data. However, exposure to most strains resulted in either high or
      low secretion levels of all cytokines tested, rather than a clear M1 or M2
      profile. In general, the Gram-negative strains induced high levels of cytokine
      secretion compared to the Gram-positive strains. Interestingly, strains of human
      origin had a higher impact on macrophages compared to strains of food origin. 

PMID- 24676764
TI  - Potentially probiotic Lactobacillus strains from traditional Kurdish cheese.
AB  - In this study, the probiotic potential of Lactobacillus strains isolated from
      traditional Kurdish cheese was investigated. The Lactobacillus strains were
      examined for resistance to gastric acidity and bile toxicity, antimicrobial
      activities, autoaggregation, coaggregation, hydrophobicity, adhesion to Caco-2
      cells, and antibiotic susceptibility. The results showed that all strains tested
      tolerate acid gastric conditions (pH 2.0 and 3.0), and all of them were bile
      resistant (at 0.3 and 1% concentration). Although no antibacterial activity was
      detected in vitro assay for the treated (neutralized to pH 6.5 and treated with
      catalase) cell-free culture supernatant (CFCS) of strains, untreated CFCS showed
      strong antagonistic activity against two known pathogens bacteria. All strains
      exhibited a strong autoaggregating phenotype and manifested a high degree of
      coaggregation with pathogens. On the other hand, majority of studied strains were
      found sensitive to different antibiotics, such as ampicillin, penicillin,
      ciprofloxacin, chloramphenicol, erythromycin, rifampicin, and tetracycline, and
      were resistant to vancomycin and streptomycin. Finally, isolated strains showed
      good hydrophobicity and adherence to Caco-2 cell line, so they could be exploited
      for food manufacture.

PMID- 24676765
TI  - Investigation of the Antimicrobial Activity of Bacillus licheniformis Strains
      Isolated from Retail Powdered Infant Milk Formulae.
AB  - This study investigated the potential antimicrobial activity of ten Bacillus
      licheniformis strains isolated from retail infant milk formulae against a range
      of indicator (Lactococcus lactis, Lactobacillus bulgaricus and Listeria innocua)
      and clinically relevant (Listeria monocytogenes, Staphylococcus aureus,
      Streptococcus agalactiae, Salmonella Typhimurium and Escherichia coli)
      microorganisms. Deferred antagonism assays confirmed that all B. licheniformis
      isolates show antimicrobial activity against the Gram-positive target organisms.
      PCR and matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry analyses indicated that four of the B. licheniformis isolates
      produce the bacteriocin lichenicidin. The remaining six isolates demonstrated a
      higher antimicrobial potency than lichenicidin-producing strains. Further
      analyses identified a peptide of ~1,422 Da as the most likely bioactive
      responsible for the antibacterial activity of these six isolates. N-terminal
      sequencing of the ~1,422 Da peptide from one strain identified it as ILPEITXIFHD.
      This peptide shows a high homology to the non-ribosomal peptides bacitracin and
      subpeptin, known to be produced by Bacillus spp. Subsequent PCR analyses
      demonstrated that the six B. licheniformis isolates may harbor the genetic
      machinery needed for the synthesis of a non-ribosomal peptide synthetase similar
      to those involved in production of subpeptin and bacitracin, which suggests that
      the ~1,422 Da peptide might be a variant of subpeptin and bacitracin.

PMID- 24676766
TI  - Beneficial effect of lantibiotic nisin in rabbit husbandry.
AB  - Nisin is a bacteriocin marketed as Nisaplin. The aim of our work was to test its
      in vivo effect in a rabbit model; its effect on phagocytic activity (PA) and
      morphometry has not so far been studied. Post-weaning rabbits (48), 5 weeks old
      (both sexes, Hycole breed), were divided into the experimental (E) and the
      control groups (C), 24 animals in each. They were fed a commercial diet with
      access to water ad libitum. Rabbits in E had nisin additionally administered to
      their drinking water (500 IU-20 MUg per animal/day) for 28 days. The experiment
      lasted 42 days. On day 28, significant decrease in coagulase-positive (CoPS)
      staphylococci and coliforms was noted (p < 0.01) in faeces of group E compared
      with C. Pseudomonads and clostridiae were also significantly reduced (p < 0.001;
      p < 0.05) and slight decrease was also in CoNS and enterococci. On day 42,
      coliforms were still significantly reduced (p < 0.001) in faeces; slight decrease
      in CoPS and pseudomonads was noted. In the caecum, significant decrease in
      pseudomonads (p < 0.05) was noted on day 28; slight decrease in coliforms. In the
      appendix slight decrease in coliforms, pseudomonads was obtained on both days. PA
      was increased significantly in E on days 28, 42 (p < 0.001). Biochemical
      parameters were not influenced; nor were volatile fatty acids or lactic acid in
      the chymus. Nisin application did not evoke oxidative stress. In group E, an
      increase in average body weight gain (about 9.4 %) was noted. The villus
      height/crypt depth ratio was not influenced; that is, resorption surface and
      functionality of mucosa were not influenced.

PMID- 24676767
TI  - Bacteriocin production and different strategies for their recovery and
      purification.
AB  - Bacteriocins from lactic acid bacteria (LAB) are a diverse group of antimicrobial
      proteins/peptides, offering potential as biopreservatives, and exhibit a broad
      spectrum of antimicrobial activity at low concentrations along with thermal as
      well as pH stability in foods. High bacteriocin production usually occurs in
      complex media. However, such media are expensive for an economical production
      process. For effective use of bacteriocins as food biopreservatives, there is a
      need to have heat-stable wide spectrum bacteriocins produced with high-specific
      activity in food-grade medium. The main hurdles concerning the application of
      bacteriocins as food biopreservatives is their low yield in food-grade medium and
      time-consuming, expensive purification processes, which are suitable at
      laboratory scale but not at industrial scale. So, the present review focuses on
      the bacteriocins production using complex and food-grade media, which mainly
      emphasizes on the bacteriocin producer strains, media used, different production
      systems used and effect of different fermentation conditions on the bacteriocin
      production. In addition, this review emphasizes the purification processes
      designed for efficient recovery of bacteriocins at small and large scale. 

PMID- 24676768
TI  - In vivo Toxicity Assessment of Antimicrobial Peptides (AMPs LR14) Derived from
      Lactobacillus plantarum Strain LR/14 in Drosophila melanogaster.
AB  - Lactic acid bacteria are known to produce antimicrobial peptides (AMPs) such as
      bacteriocins which can be employed to control pathogens and food spoilage
      microorganisms. However, their possible role as toxic agents against a eukaryotic
      system still remains unexplored. The present study deals with the in vivo
      evaluation of acute toxic effect of AMPs LR14, a mixture of AMPs isolated from
      Lactobacillus plantarum LR/14 on Drosophila melanogaster. The fly was used as a
      model system to measure the extent of toxicity of these peptides. The results
      showed that concentrations below 10 mg/ml are not significantly effective. When
      exposed to 10 mg/ml of AMPs LR14, acute toxic effect and a significant delay in
      the developmental cycle of the fly could be observed. Also, the weight and size
      of the flies were significantly reduced upon ingestion of these peptides. Higher
      concentrations (beyond 15 mg/ml) exerted a strong larvicidal effect. Detailed
      analysis on larval tissues and adult germ cells of the insect revealed deformity
      in cellular architecture, DNA fragmentation, and premature apoptosis, confirming
      that the peptides have a dose-dependent toxic property. Our studies provide the
      first information on the role of AMPs LR14 as an insecticidal agent.

PMID- 24676769
TI  - Effects of ketoprofen for prevention of postoperative cognitive dysfunction in
      aged rats.
AB  - Postoperative cognitive dysfunction is a common geriatric complication that may
      be associated with increased mortality. Here, we investigated the effects of
      postoperative analgesia with ketoprofen on cognitive functions in aged animals
      and compared its effectiveness to morphine. Rats were randomly allocated to one
      of four groups: isoflurane anesthesia without surgery (group C), isoflurane
      anesthesia with laparotomy (group IL), and isoflurane anesthesia with laparotomy
      plus postoperative analgesia with ketoprofen or morphine. There was no difference
      in postoperative locomotor activity among groups. In group IL, postoperative pain
      levels assessed by the Rat Grimace Scale significantly increased until 8 h after
      surgery, which was similarly inhibited by both ketoprofen and morphine. Cognitive
      function was assessed using radial arm maze testing for 12 consecutive days from
      postoperative day 3. Results showed that the number of memory errors in group IL
      were significantly higher than those in goup C. However, both ketoprofen and
      morphine could attenuate the increase in memory errors following surgery to a
      similar degree. Conversely, ketoprofen showed no effect on cognitive function in
      the nonsurgical rats that did not experience pain. Our findings suggest that
      postoperative analgesia with ketoprofen can prevent the development of surgery
      associated memory deficits via its pain-relieving effects.

PMID- 24676770
TI  - In vitro- in vivo correlation's dissolution limits setting.
AB  - PURPOSE: In vitro in vivo correlation (IVIVC) is a biopharmaceutical tool
      recommended for use in formulation development. When validated, IVIVC can be used
      to set dissolution limits and, based on the dissolution limits, as a surrogate
      for an in vivo study. The purpose of this paper is to study the various methods
      used to fix dissolution limits. METHODS: Fixing dissolution limits is not a
      straightforward process; various approaches exist. The classical +/-10% of
      dissolution limits was compared to the recommended +/-10% of Cmax and AUC and to
      an innovative back calculation of the 90% CI. Based on simulated values the
      influence of the calculation method as well as of the variability of the results
      and pharmacokinetic processes was investigated. RESULTS: Depending upon the
      method, the results are different and their comparison leads to possible rules.
      It appears that the usage of a back calculation of a 90% CI is an accurate and
      advantageous method when intra-individual variability associated with the drug is
      low. Those findings are in accordance with the current practice of IVIVC, which
      is not recommended for highly variable drugs. CONCLUSIONS: The approach of using
      a 90% CI allows the intra-subject variability to be taken into account and fixes
      limits that ensure a greater chance to show acceptable BE, in case of reasonable
      intra-subject variability, leading to setting broader in vitro dissolution limits
      compared to classical solutions.

PMID- 24676771
TI  - Unresectable perineal cuniculatum carcinoma: partial remission using systemic
      isotretinoin and interferon-alpha2a therapy.

PMID- 24676773
TI  - Protective effect of fluvastatin on influenza virus infection.
AB  - Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and have
      pleiotropic effects. It has been suggested that statins may be a potential
      treatment during the next influenza pandemic. In a previous study we found that a
      statin/caffeine combination protects BALB/c mice against Influenza A, subtypes
      haemagglutinin type 5 and neuraminidase type 1 (H5N1), H3N2 and H1N1 infection.
      The effect of statins alone on influenza virus infection, however, is not known.
      In this study, it was investigated whether fluvastatin is capable of inhibiting
      influenza A virus replication in vitro. The results demonstrated that the
      synthesis of viral RNA and protein was affected by fluvastatin treatment. Virus
      production was markedly reduced when fluvastatin was administered simultaneously
      with the virus; however, a greater inhibition was observed when fluvastatin was
      added following viral adsorption. The selectivity index [SI; 50% cytotoxic
      concentration (CC50)/50% inhibition concentration (IC50)], however, was only 21.
      It was further demonstrated that fluvastatin protects host cells against
      influenza-induced inflammation by reducing the production of tumour necrosis
      factor-alpha, interleukin 8 and interferon gamma. In conclusion, the results
      demonstrated that fluvastatin exerted a minor inhibitory effect on influenza
      virus infection, which involved anti-inflammatory activities.

PMID- 24676774
TI  - Mannose-binding lectin promotes local microvascular thrombosis after transient
      brain ischemia in mice.
AB  - BACKGROUND AND PURPOSE: Several lines of evidence support the involvement of
      mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the
      complement system facilitates thrombin activation and clot formation under
      certain experimental conditions. In the present study, we examine whether MBL
      promotes thrombosis after ischemia/reperfusion and influences the course and
      prognosis of ischemic stroke. METHODS: Middle cerebral artery
      occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT;
      n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative
      cerebral blood flow was monitored up to 6 hours after middle cerebral artery
      occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the
      brain vasculature and plasma, and the effects of thrombin inhibitor argatroban
      were evaluated to assess the role of MBL in thrombin activation. RESULTS: Infarct
      volumes and neurological deficits were smaller in MBL knockout mice than in WT
      mice. Relative cerebral blood flow values during middle cerebral artery occlusion
      and at reperfusion were similar in both groups, but decreased during the next 6
      hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain
      vessels and a better outcome after argatroban treatment. In contrast, argatroban
      did not improve the outcome in MBL knockout mice. CONCLUSIONS: MBL promotes brain
      damage and functional impairment after brain ischemia/reperfusion in mice. These
      effects are secondary to intravascular thrombosis and impaired relative cerebral
      blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout
      mice, emphasizing a role of MBL in local thrombus formation in acute
      ischemia/reperfusion.

PMID- 24676775
TI  - Epidemiology of moyamoya disease in Taiwan: a nationwide population-based study.
AB  - BACKGROUND AND PURPOSE: Previous studies have shown regional and temporal
      variations in epidemiological features of moyamoya disease, but population-based
      studies in regions other than Japan are limited. We investigated the incidence
      and patients characteristics of moyamoya disease during 12 years in Taiwan using
      claims databases of a universal health insurance system. METHODS: From the
      inpatient databases of the Taiwan National Health Insurance program, we
      identified subjects who had an initial hospitalization with moyamoya disease and
      had been underwent cerebral angiography as incidence cases during 2000 to 2011.
      The incidence and the patient characteristics were described by age and time
      periods of the hospitalization. RESULTS: During the 12-year period, 422 patients
      were identified, representing an annual incidence of 0.15 per 100,000 person
      years. Adults exhibited an upward trend in incidence with an incidence rate ratio
      of 1.74 (95% confidence interval [1.17-2.58]) in years 2010 to 2011 comparing
      with years 2000 to 2001. However, children had a decreased incidence except a
      slightly increase in the last 2 years. Compared with patients hospitalized during
      2000 to 2005, patients identified during 2006 to 2011 had greater women-to-men
      ratio (1.7 versus 1.1, P=0.048). Children were more likely to have comorbid
      epilepsy than were adult patients (25.0% versus 3.4%, P=0.002). Hemorrhagic
      stroke was rare among pediatric patients but presented more frequently in adults.
      However, ischemic stroke was more prevalent in both groups. CONCLUSIONS: The
      incidence of moyamoya disease has increased in adults but not in children from
      2000 to 2011 in Taiwan. Sex ratio and comorbid conditions differed by age and
      study period.

PMID- 24676776
TI  - Reduction of length of stay and costs through the implementation of clinical
      pathways for stroke management in China.

PMID- 24676777
TI  - Impaired glucose regulation predicted 1-year mortality of Chinese patients with
      ischemic stroke: data from abnormal glucose regulation in patients with acute
      stroke across China.
AB  - BACKGROUND AND PURPOSE: It remains uncertain if impaired glucose regulation (IGR)
      as a predictor for stroke outcomes. This study aimed at observing the effect of
      IGR on the 1-year outcomes in Chinese patients with ischemic stroke. METHODS:
      Patients with acute ischemic stroke were recruited consecutively in
      multihospitals across China. Oral glucose tolerance test was performed to
      identify IGR. Cox proportion hazard model was performed to investigate the effect
      of IGR on 1-year mortality or stroke recurrence in patients with ischemic stroke.
      RESULTS: The study recruited 2639 patients with ischemic stroke. IGR was shown as
      an independent risk factor for the mortality of patients with ischemic stroke
      (hazard ratio [95% confidence interval], 3.088 [1.386-6.884]; P=0.006). However,
      IGR showed no significant effects on the dependency or stroke recurrence of
      patients (P=0.540 and 0.618, respectively). CONCLUSIONS: IGR was an independent
      predictor for the mortality of patients with ischemic stroke. IGR should be
      highlighted and intervened actively in the patients with ischemic stroke.

PMID- 24676778
TI  - Cognitive impairment and risk of stroke: a systematic review and meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND AND PURPOSE: Cognitive impairment is linked to vascular risk factors
      and brain vascular pathologies. Several studies have tested whether subjects with
      cognitive impairment have higher risk for stroke. The aim of this study was to
      systematically review available evidence on the association between cognitive
      impairment and risk of stroke to obtain precise effect estimates of the
      association and to identify which cognitive domains associate most with incident
      stroke. METHODS: PubMed, EMBASE, and Web of Science were searched from January 1,
      1980, to October 1, 2013, without language restriction. Only prospective cohort
      studies were included. From each study, data on the association between cognitive
      impairment and stroke estimated with hazard ratios or relative risks with 95%
      confidence interval (CI) were extracted. For each study, risk of stroke per SD
      lower performance in various cognitive tests was calculated. RESULTS: Twelve
      studies were included, comprising 82,899 participants of whom 3043 had an
      incident stroke. The pooled relative risk per SD lower global cognitive
      performance was 1.19 (95% CI, 1.12-1.27). Each SD lower score in executive
      function or attention was associated with 1.14-fold (95% CI, 1.06-1.24) higher
      risk of stroke. Lower scores in memory were associated with 1.07-fold (95% CI,
      1.02-1.12) higher risk of stroke, and lower scores in language were associated
      with 1.08-fold (95% CI, 1.02-1.16) higher risk of stroke. CONCLUSIONS: Cognitive
      impairment is associated with higher risk of stroke. The associations were not
      significantly different for executive function, memory, and language.

PMID- 24676779
TI  - Consistency of blood pressure control after ischemic stroke: prevalence and
      prognosis.
AB  - BACKGROUND AND PURPOSE: Blood pressure (BP) reduction lowers vascular risk after
      stroke; however, little is known about the relationship between consistency of BP
      control and risk of subsequent vascular events. METHODS: In this post hoc
      analysis of the Vitamin Intervention for Stroke Prevention trial (n=3680),
      individuals with recent (<120 days) stroke, followed up for 2 years, were divided
      according to proportion of visits in which BP was controlled (<140/90 mm Hg):
      <25%, 25% to 49%, 50% to 74%, and >=75%. Multivariable models adjusting for
      demographic and clinical variables determined the association between consistency
      of BP control versus primary (stroke) and secondary (stroke, myocardial
      infarction, or vascular death) outcomes. RESULTS: Only 30% of participants had BP
      controlled >=75% of the time. Consistency of BP control affected outcomes in
      individuals with baseline systolic BP>132 mm Hg. Among individuals with baseline
      systolic BP>75th percentile (>153 mm Hg), risks of primary and secondary outcomes
      were lower in those with BP controlled >=75% versus <25% of visits (adjusted
      hazard ratio, 0.46; 95% confidence interval, 0.26-0.84 and adjusted hazard ratio,
      0.51; 95% confidence interval, 0.32-0.82). Individuals with mean follow-up
      BP<140/90 mm Hg had lower risk of primary and secondary outcomes than those with
      BP>=140/90 mm Hg (adjusted hazard ratio, 0.76; 95% confidence interval, 0.59-0.98
      and adjusted hazard ratio, 0.76; 95% confidence interval, 0.62-0.92).
      CONCLUSIONS: In this rigorous clinical trial, fewer than one third of patients
      with stroke had BP controlled >=75% of the time for 2 years. Furthermore,
      consistency of BP control among those with elevated baseline systolic BP was
      linked to reduction in risk of recurrent stroke and stroke, myocardial
      infarction, and vascular death.

PMID- 24676780
TI  - Age dependence of risk factors for stroke and death in young patients with atrial
      fibrillation: a nationwide study.
AB  - BACKGROUND AND PURPOSE: The risk of stroke and death in patients with atrial
      fibrillation is strongly associated with age and concomitant comorbidities. The
      aim of this study was to examine the age dependence of risk factors for stroke
      and mortality in young patients with atrial fibrillation. METHODS: This study is
      a population-based cohort study of 30- to 65-year-old patients with atrial
      fibrillation and diagnosed during 2000 to 2011, identified by record linkage
      between nationwide Danish registries. Cox regression models were used to estimate
      the risk of stroke and mortality according to risk factors within age groups: 30
      to 50, 50 to 65, and 65 to 75 years. RESULTS: We identified 73,799 nonvalvular
      atrial fibrillation patients, of which 37,782 (51.2%) were <65 years old (mean
      age 62.8). A higher modified cardiac failure or dysfunction, hypertension, age 75
      (doubled), diabetes, stroke (doubled), vascular disease, age 65-74 and sex
      category (female) score (CHA2DS2-VASc score) was associated with decreased
      survival probability in all age groups. The overall incidence of stroke per year
      for 1 year (5 years) follow-up was 1.2% (0.6%), 3.5% (1.6%), and 5.6% (2.8%),
      respectively, for the age groups of 30 to 50, 50 to 65, and 65 to 75. Overall,
      risk factors such as previous stroke, heart failure, vascular disease, diabetes
      mellitus, and hypertension remained independent predictors of stroke and death in
      patients<65 years old with nonvalvular atrial fibrillation. CONCLUSIONS: The
      CHA2DS2-VASc score is an applicable tool for all age groups and in nonvalvular
      atrial fibrillation patients<65 years old, the same risk factors apply.

PMID- 24676781
TI  - Palliative and end-of-life care in stroke: a statement for healthcare
      professionals from the American Heart Association/American Stroke Association.
AB  - BACKGROUND AND PURPOSE: The purpose of this statement is to delineate basic
      expectations regarding primary palliative care competencies and skills to be
      considered, learned, and practiced by providers and healthcare services across
      hospitals and community settings when caring for patients and families with
      stroke. METHODS: Members of the writing group were appointed by the American
      Heart Association Stroke Council's Scientific Statement Oversight Committee and
      the American Heart Association's Manuscript Oversight Committee. Members were
      chosen to reflect the diversity and expertise of professional roles in delivering
      optimal palliative care. Writing group members were assigned topics relevant to
      their areas of expertise, reviewed the appropriate literature, and drafted
      manuscript content and recommendations in accordance with the American Heart
      Association's framework for defining classes and level of evidence and
      recommendations. RESULTS: The palliative care needs of patients with serious or
      life-threatening stroke and their families are enormous: complex decision making,
      aligning treatment with goals, and symptom control. Primary palliative care
      should be available to all patients with serious or life-threatening stroke and
      their families throughout the entire course of illness. To optimally deliver
      primary palliative care, stroke systems of care and provider teams should (1)
      promote and practice patient- and family-centered care; (2) effectively estimate
      prognosis; (3) develop appropriate goals of care; (4) be familiar with the
      evidence for common stroke decisions with end-of-life implications; (5) assess
      and effectively manage emerging stroke symptoms; (6) possess experience with
      palliative treatments at the end of life; (7) assist with care coordination,
      including referral to a palliative care specialist or hospice if necessary; (8)
      provide the patient and family the opportunity for personal growth and make
      bereavement resources available if death is anticipated; and (9) actively
      participate in continuous quality improvement and research. CONCLUSIONS:
      Addressing the palliative care needs of patients and families throughout the
      course of illness can complement existing practices and improve the quality of
      life of stroke patients, their families, and their care providers. There is an
      urgent need for further research in this area.

PMID- 24676782
TI  - Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1alpha
      functional interplay.
AB  - The molecular mechanisms by which glioblastoma multiforme (GBM) refracts and
      becomes resistant to radiotherapy treatment remains largely unknown. This
      radioresistance is partly due to the presence of hypoxic regions, which are
      frequently found in GBM tumors. We investigated the radiosensitizing effects of
      MEK/ERK inhibition on GBM cell lines under hypoxic conditions. Four human GBM
      cell lines, T98G, U87MG, U138MG and U251MG were treated with the MEK/ERK
      inhibitor U0126, the HIF-1alpha inhibitor FM19G11 or gamma-irradiation either
      alone or in combination under hypoxic conditions. Immunoblot analysis of specific
      proteins was performed in order to define their anti-oncogenic or
      radiosensitizing roles in the different experimental conditions. MEK/ERK
      inhibition by U0126 reverted the transformed phenotype and significantly enhanced
      the radiosensitivity of T98G, U87MG, U138MG cells but not of the U251MG cell line
      under hypoxic conditions. U0126 and ERK silencing by siRNA reduced the levels of
      DNA protein kinase catalytic subunit (DNA-PKcs), Ku70 and K80 proteins and
      clearly reduced HIF-1alpha activity and protein expression. Furthermore, DNA-PKcs
      siRNA-mediated silencing counteracted HIF-1alpha activity and downregulated
      protein expression suggesting that ERKs, DNA-PKcs and HIF-1alpha cooperate in
      radioprotection of GBM cells. Of note, HIF-1alpha inhibition under hypoxic
      conditions drastically radiosensitized all cell lines used. MEK/ERK signal
      transduction pathway, through the sustained expression of DNA-PKcs, positively
      regulates HIF-1alpha protein expression and activity, preserving GBM
      radioresistance in hypoxic condition. 

PMID- 24676784
TI  - Opportunities and challenges of next-generation DNA sequencing for breast units.
AB  - BACKGROUND: The aim of this review is to introduce the topic of next-generation
      DNA sequencing, a new technology that is being introduced into clinical practice,
      and to explain the potential impact for breast cancer surgeons and the wider
      breast cancer multidisciplinary team. METHODS: The PubMed database was used to
      identify relevant studies relating to breast cancer genetics. This evidence was
      then used to provide context and background information to demonstrate how next
      generation sequencing (NGS) might change breast cancer practice. RESULTS: With
      NGS, breast cancer clinicians will know whether their patients carry high-risk
      mutations in genes, such as BRCA1 or BRCA2, before the start of treatment. This
      could alter treatment decisions; for instance, more women might opt for
      mastectomy instead of breast-conserving surgery, or for bilateral rather than
      unilateral surgery. CONCLUSION: The introduction of NGS will have a significant
      impact on breast cancer services in the near future. Speed of testing will
      improve in regions of the world where NGS is adopted in place of conventional
      sequencing, and, as costs decrease, genetic testing will also become accessible
      and realistic in less well funded health economies. This will create
      opportunities to improve patient treatment and challenges for the breast cancer
      multidisciplinary team.

PMID- 24676783
TI  - Mechanistic insights and characterization of sickle cell disease-associated
      cardiomyopathy.
AB  - BACKGROUND: Cardiovascular disease is an important cause of morbidity and
      mortality in sickle cell disease (SCD). We sought to characterize sickle cell
      cardiomyopathy using multimodality noninvasive cardiovascular testing and
      identify potential causative mechanisms. METHODS AND RESULTS: Stable adults with
      SCD (n=38) and healthy controls (n=13) prospectively underwent same day
      multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator
      first pass myocardial perfusion, and late gadolinium enhancement imaging),
      transthoracic echocardiography, and applanation tonometry. Compared with
      controls, patients with SCD had severe dilation of the left ventricle (124+/-27
      vs 79+/-12 mL/m(2)), right ventricle (127+/-28 vs 83+/-14 mL/m(2)), left atrium
      (65+/-16 vs 41+/-9 mL/m(2)), and right atrium (78+/-17 vs 56+/-17 mL/m(2); P<0.01
      for all). Patients with SCD also had a 21% lower myocardial perfusion reserve
      index than control subjects (1.47+/-0.34 vs 1.87+/-0.37; P=0.034). A significant
      subset of patients with SCD (25%) had evidence of late gadolinium enhancement,
      whereas only 1 patient had evidence of myocardial iron overload. Diastolic
      dysfunction was present in 26% of patients with SCD compared with 8% in controls.
      Estimated filling pressures (E/e', 9.3+/-2.7 vs 7.3+/-2.0; P=0.0288) were higher
      in patients with SCD. Left ventricular dilation and the presence of late
      gadolinium enhancement were inversely correlated to hepatic T2* times (ie,
      hepatic iron overload because of frequent blood transfusions; P<0.05 for both),
      whereas diastolic dysfunction and increased filling pressures were correlated to
      aortic stiffness (augmentation pressure and index, P<0.05 for all). CONCLUSIONS:
      Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some
      patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction,
      and only rarely myocardial iron overload. Left ventricular dilation and
      myocardial fibrosis are associated with increased blood transfusion requirements,
      whereas left ventricular diastolic dysfunction is predominantly correlated with
      increased aortic stiffness. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01044901.

PMID- 24676786
TI  - Analyzing the global chromatin structure of keratinocytes by MNase-seq.
AB  - Eukaryotic DNA is wrapped around histone octamers, known as nucleosomes, in an
      orderly fashion that provides the primary structure of chromatin organization.
      The compaction of DNA into nucleosomal repeats not only allows the tight
      packaging of the large eukaryotic genomes into the nucleus, it also dictates the
      accessibility of genetic information. Thus, in order to understand how
      nucleosomes can affect the dynamics of DNA-protein interactions, such as those
      associated with transcriptional regulatory mechanisms, it is important to define
      nucleosomal positioning and occupancy along genomic DNA. Here we describe a
      method that relies on the enzymatic activity of micrococcal nuclease (MNase) to
      determine nucleosomal footprints and boundaries. By pairing this technique with
      next generation sequencing techniques (i.e., MNase-seq), it is possible to
      generate a genome-wide detailed map of chromatin architecture. 

PMID- 24676785
TI  - High-throughput cell aggregate culture for stem cell chondrogenesis.
AB  - Cell aggregate culture is a widely used, reliable system for promoting
      chondrogenic differentiation of stem cells. A high-throughput cell pellet culture
      enables screening of various soluble factors for their effects on stem cell
      function and chondrogenesis. In this protocol, we report a platform that allows
      the formation of stem cell aggregates in a 96-well plate format. Specifically,
      stem cells are centrifuged to form high-density pellets, mimicking mesenchymal
      condensation. The cell aggregates can be differentiated into chondrocytes when
      cultured in chondrogenic medium for 4 weeks. Such a technique is compatible for
      high-throughput screening and can be very useful for optimizing conditions for
      cartilage tissue engineering. 

PMID- 24676787
TI  - High coexpression of CCL2 and CX3CL1 is gender-specifically associated with good
      prognosis in soft tissue sarcoma patients.
AB  - Chemokines are involved in both the negative and positive regulation of
      inflammatory processes, angiogenesis and cancer/cancer stem cell proliferation as
      well as the chemoattraction of tumor cells to metastatic sites. The aim of this
      study was to measure the mRNA expression levels of three chemokines, CCL2, CCL7
      and CX3CL1, in soft tissue sarcomas (STSs) and to assess the correlations between
      these levels as well as their correlations with clinicopathological data and the
      disease-specific survival of STS patients. The mRNA levels of CCL2, CCL7 and
      CX3CL1 were analyzed in tumor tissues from 126 STS patients using qPCR. Low mRNA
      expression of CCL2 and CX3CL1 was significantly correlated with a worse prognosis
      (RR = 1.98; p = 0.019 and RR = 2.10; p = 0.014; multivariate Cox's regression
      analysis). A combined low expression of CCL2 and CX3CL1 was associated with a
      significantly increased risk of tumor-related death as compared to patients with
      high expression levels of both chemokines (RR = 3.08; p = 0.003). A gender
      specific multivariate analysis revealed that female STS patients with low CX3CL1
      mRNA expression had a 3.46-fold increased risk of death (p = 0.004). Low
      expression of both CCL2 and CX3CL1 mRNAs resulted in an additive 5.37-fold
      increased risk of tumor-related death (p = 0.003) as compared to those with high
      expression of both parameters in female patients. In conclusion, this is the
      first study to show a significant correlation between combined low expression of
      CCL2 and CX3CL1 and a poor prognosis for STS patients, particularly in female
      patients. 

PMID- 24676789
TI  - Translation, cross-cultural adaptation and validation of the French version of
      the Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI) scale.
AB  - PURPOSE: The aim of this study was to translate, adapt and validate in French the
      Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI), a 12-item
      English language scale assessing the psychological impact of returning to sports
      after ACL reconstruction. METHODS: The ACL-RSI scale was forward and back
      translated, cross-culturally adapted and validated using international
      guidelines. The study population included all patients who were active in sports
      and underwent primary arthroscopic ACL reconstruction. The control group included
      subjects with no history of knee trauma. At the 6-month follow-up, the study
      population completed the ACL-RSI scale twice within 3-4 days, Knee injury and
      Osteoarthritis Outcome Score (KOOS) and subjective International Knee
      Documentation Committee (IKDC) scores. Statistical tests assessed the construct
      validity, discriminant validity, internal consistency, reliability and
      feasibility of the ACL-RSI scale. RESULTS: Ninety-one patients with ACL tears and
      98 control subjects were included: mean age 31.7 +/- 8.1 and 21.8 +/- 2,
      respectively. The ACL-RSI scores were correlated with all KOOS sub-categories (r
      = 0.22-0.64, p < 0.05) as well as the subjective IKDC score (r = 0.42, p <
      0.00001). The mean scores of the study and control groups were significantly
      different (62.8 +/- 19.4 vs. 89.6 +/- 11.5, p < 0.00001), and scores were
      significantly better in patients who returned to the same sport (72.1 +/- 21.4
      vs. 60.3 +/- 18.1, p = 0.008). Internal consistency was high (alpha = 0.96). Test
      retest reproducibility was excellent: rho = 0.90 (0.86-0.94), p < 0.00001.
      Administration time was 1.32 +/- 0.7 mn, and all items were answered. CONCLUSION:
      This study showed that the cross-cultural adaptation of the English version of
      the ACL-RSI was successful and validated in a French-speaking population. The
      discriminant capacity of the scale between patients who underwent reconstruction
      and healthy subjects was confirmed. LEVEL OF EVIDENCE: II.

PMID- 24676790
TI  - Midterm results following medial closed wedge distal femoral osteotomy stabilized
      with a locking internal fixation device.
AB  - PURPOSE: Aim of this study was to evaluate the subjective and radiological
      outcome and to evaluate the complications of a medial closing wedge osteotomy at
      the femur for lateral osteoarthritis with genu valgum. METHODS: Twenty-three
      patients with grade III to IV cartilage damage and valgus knee alignment were
      treated with medial closing wedge osteotomy at the distal femur. The osteotomy
      was stabilized with an internal plate fixator. Age varied between 25 and 55 years
      (mean 47 years). One patient was lost to final follow-up. RESULTS: After 3.5
      years, all Knee Osteoarthritis Outcome Score (KOOS) subitems increased
      significantly. There was no significant difference in the subgroup analysis of
      KOOS subitems for patients with and without microfracture or age (>50 vs. <50
      years). There were no perioperative complications. One patient had an
      overcorrection. All, but one osteotomy, showed stable bone healing. There was a
      loss of correction due to delayed bone healing in one case. Possible explanations
      for this complication were injury of the lateral cortex or smoking. This case
      required revision with bone graft and an additional lateral plate. In no case, a
      conversion to an endoprosthesis was necessary. CONCLUSION: The femoral medial
      closing wedge osteotomy is a surgical method for improving symptoms of lateral
      osteoarthritis in the valgus knee. LEVEL OF EVIDENCE: IV.

PMID- 24676791
TI  - The efficacy and safety of onabotulinumtoxinA in treating idiopathic OAB: A
      systematic review and meta-analysis.
AB  - AIM: We carried out a systematic review and meta-analysis to assess the efficacy
      and safety of the drug for treating idiopathic OAB. METHODS: A literature review
      was performed to identify all published randomized double-blind, placebo
      controlled trials of onabotulinumtoxinA for the treatment of idiopathic OAB. The
      search included the following databases: MEDLINE, EMBASE, and the Cochrane
      Controlled Trials Register. The reference lists of the retrieved studies were
      also investigated. RESULTS: Eight publications involving a total of 1,320
      patients were used in the analysis, including six RCTs that compared
      onabotulinumtoxinA with placebo. OnabotulinumtoxinA significantly decreased the
      mean number of urinary incontinence (UI) per day -2.77 versus -1.01 (the
      standardized mean difference (SMD) = -1.68, 95% CI = -2.06 to -1.31, P <
      0.00001); the mean number of micturitions per day -1.61 versus -0.87 (SMD = 
      1.82, 95% CI = -2.61 to -1.02, P < 0.00001); maximum cystometric capacity (MCC)
      91.39 versus 32.32 (SMD = 63.82, 95% CI = 38.14 to 89.50, P < 0.00001) and volume
      voided 44.29 versus 7.36 (SMD = 33.05, 95% CI = 22.45 to 43.66, P < 0.00001)
      versus placebo and 29.20% versus 7.95% of patients became incontinence-free (odds
      ratio [OR] = 4.89, 95% confidence interval [CI] = 3.11 to 7.70, P < 0.00001).
      Safety assessments primarily localized to the urinary tract indicated
      onabotulinumtoxinA were often associated with complications resulting from
      postvoid residuals (PVR; P < 0.00001), urinary tract infections (UTI; P <
      0.00001) and clean intermittent catheterization (CIC; P < 0.00001). CONCLUSION:
      This meta-analysis indicates that onabotulinumtoxinA to be an effective treatment
      for idiopathic overactive bladder symptoms with side effects primarily localized
      to urinary tract.

PMID- 24676792
TI  - Lactarius deliciosus and Pinus radiata in New Zealand: towards the development of
      innovative gourmet mushroom orchards.
AB  - The cultivation of Lactarius deliciosus (saffron milk cap) in New Zealand began
      in 2002 when fruiting bodies were produced in an Otago plantation of Pinus
      radiata seedlings artificially mycorrhized by L. deliciosus. In 2007, 42 P.
      radiata seedlings mycorrhized by L. deliciosus under controlled conditions were
      planted in a grass field at Plant and Food Research (Lincoln, Canterbury). The
      effects of pine bark mulch application and initial degree of mycorrhization of
      seedlings were examined to determine their influence on tree growth, development
      of mycorrhizae (i.e. their multiplication on the root system and their degree of
      branching) and fruiting body production. Mulch application increased tree growth
      significantly over 4 years. High initial mycorrhization slightly stimulated tree
      growth over 2 years. The initial degree of mycorrhization was positively, but not
      strongly, related to the persistence and development of L. deliciosus mycorrhizae
      and rhizomorphs based on root sample analyses 2 years after planting. However,
      mulching strongly reduced the proportion of highly branched L. deliciosus
      mycorrhizae compared with poorly ramified ones. A positive correlation was
      observed between the fruiting of L. deliciosus and the development of
      mycorrhizae. Mulching delayed the onset of fruiting body production. In 2010,
      fruiting bodies were produced only from non-mulched trees with eight of these (38
      %) producing a total of 12 fruiting bodies. In 2011, 19 non-mulched trees (90 %)
      and 9 mulched trees (45 %) produced 143 and 47 fruiting bodies, respectively,
      totalling 190 fruiting bodies. By 2012, 19 non-mulched trees (90 %) and 13
      mulched trees (65 %) produced 333 and 236 fruiting bodies, respectively,
      totalling 569 fruiting bodies (c. 30 kg). This study presents new information on
      factors influencing the onset of fruiting and the development of yields in a
      plantation of P. radiata mycorrhized by L. deliciosus. Projected yields as high
      as c. 300 kg/ha from the third year of production reiterate the feasibility of
      farming saffron milk cap in P. radiata plantations in New Zealand. Continued
      monitoring of this site and development of similar trials will provide important
      knowledge for the optimisation of yields in commercial saffron milk cap orchards.

PMID- 24676793
TI  - Expression of growth hormone receptor, plakoglobin and NEDD9 protein in
      association with tumour progression and metastasis in human breast cancer.
AB  - Breast cancer is the most frequently diagnosed cancer and the leading cause of
      cancer-related deaths among female population worldwide. Metastases are the
      common cause of morbidity and mortality in breast cancer and can remain latent
      for several years after surgical removal of the primary tumour. Thus, the
      identification and functional characterisation of molecular factors that promote
      oncogenic signalling in mammary tumour development and progression could provide
      new entry points for designing targeted therapeutic strategies for metastatic
      breast cancer. In the present study, we investigated the expression of proteins
      involved in cell signalling (growth hormone receptor (GHR) and NEDD9) and cell
      cell adhesion (plakoglobin) in epithelial and stromal compartments of primary
      ductal invasive breast carcinomas and their axillary lymph node metastases versus
      non-metastatic tumours. Obtained data revealed remarkable increase in the
      expression levels of GHR and NEDD9 proteins in both epithelial and stromal
      components of axillary lymph node metastases in comparison with those of non
      metastatic tumours, suggesting that the expression of these two proteins may
      provide biomarkers for tumour aggressiveness. 

PMID- 24676794
TI  - Genetic variants of NQO1 gene increase bladder cancer risk in Indian population
      and meta-analysis.
AB  - NAD(P)H: quinone oxidoreductase (NQO1) is cytosolic enzymes that plays a role in
      protection against natural and xenobiotic quinones. This enzyme also protects
      cells from oxidative damage by preventing the generation of reactive oxygen
      species and reducing environmental carcinogens. The study included 200 bladder
      cancer (BC) patients and 200 healthy control individuals that had been matched by
      age and sex, and were of similar ethnicity. NQO1 Exon 4 (C > T) and Exon 6 (C >
      T) gene polymorphisms were genotyped by polymerase chain reaction-restricted
      fragment length polymorphism (PCR-RFLP). We also performed a meta-analysis of 12
      studies including the present study (2,286 cases and 2,294 controls) for NQO1
      Exon 6 (C > T) polymorphism and overall BC susceptibility. Variant genotype TT of
      NQO1 Exon 6 (C > T) demonstrated a significant risk with BC (OR = 2.54; p =
      0.016). T allele carriers (CT + TT) (OR = 1.60; p = 0.020) of NQO1 Exon 6, as
      well as T allele (OR = 1.60; p = 0.004) were at higher risk of BC. The diplotype
      C-T was observed to be associated with a significant increase BC risk (Bonferroni
      corrected p value, Pc = 0.02; OR = 1.61). In addition, a meta-analysis of the
      Exon 6 (C > T) polymorphism and BC risk showed that the variant of NQO1 Exon 6
      genotypes was associated with an overall increased risk of BC, which was
      consistent with the results of the present study. However, none of these two
      polymorphisms were associated with tobacco smoking, tumor progression, and risk
      of BC recurrence in patients treated with BCG immunotherapy. Our results
      suggested that the NQO1 Exon 6 (C > T) may be associated with BC risk and could
      be a useful marker for primary prevention and development of BC in Indian
      population. Larger studies are required to validate these findings in diverse
      populations and of different ethnicities.

PMID- 24676795
TI  - X1-homologous genes family as central components in biotic and abiotic stresses
      response in maize (Zea mays L.).
AB  - X1-homologous genes (XHS) encode plant specific proteins containing three basic
      domains (XH, XS, zf-XS). In spite of their physiological importance, systematic
      analyses of ZmXHS genes have not yet been explored. In this study, we isolated
      and characterized ten ZmXHS genes in a whole-of-genome analysis of the maize
      genome. A total of ten members of this family were identified in maize genome.
      The ten ZmXHS genes were distributed on seven maize chromosomes. Multiple
      alignment and motif display results revealed that most ZmXHS proteins share all
      the three conserved domains. Putative cis-elements involved in abiotic stress
      responsive, phytohormone, pollen-specific and quantitative, seed development and
      germination, light and circadian rhythms regulation, Ca(2+)-responsive, root hair
      cell-specific, and CO(2)-responsive transcriptional activation were observed in
      the promoters of ZmXHS genes. Yeast hybrid assay revealed that the XH domain of
      ZmXHS5 was necessary for interaction with itself and ZmXHS2. Microarray data
      showed that the ZmXHS genes had tissue-specific expression patterns in the maize
      developmental steps and biotic stresses response. Quantitative real-time PCR
      analysis results indicated that, except ZmXHS9, the other nine ZmXHS genes were
      induced in the seedling leaves by at least one of the four abiotic stresses
      applied.

PMID- 24676796
TI  - Comparative proteomic analysis reveals that T3SS, Tfp, and xanthan gum are key
      factors in initial stages of Citrus sinensis infection by Xanthomonas citri
      subsp. citri.
AB  - The bacteria Xanthomonas citri subsp. citri (Xac) is the causal agent of citrus
      canker. The disease symptoms are characterized by localized host cell hyperplasia
      followed by tissue necrosis at the infected area. An arsenal of bacterial
      pathogenicity- and virulence-related proteins is expressed to ensure a successful
      infection process. At the post-genomic stage of Xac, we used a proteomic approach
      to analyze the proteins that are displayed differentially over time when the
      pathogen attacks the host plant. Protein extracts were prepared from infectious
      Xac grown in inducing medium (XAM1) for 24 h or from host citrus plants for 3 or
      5 days after infection, detached times to evaluate the adaptation and virulence
      of the pathogen. The protein extracts were proteolyzed, and the peptides derived
      from tryptic digestion were investigated using liquid chromatography and tandem
      mass spectrometry. Changes in the protein expression profile were compared with
      the Xac genome and the proteome recently described under non-infectious
      conditions. An analysis of the proteome of Xac under infectious conditions
      revealed proteins directly involved in virulence such as the type III secretion
      system (T3SS) and effector proteins (T3SS-e), the type IV pilus (Tfp), and
      xanthan gum biosynthesis. Moreover, four new mutants related to proteins detected
      in the proteome and with different functions exhibited reduced virulence relative
      to the wild-type proteins. The results of the proteome analysis of infectious Xac
      define the processes of adaptation to the host and demonstrate the induction of
      the virulence factors of Xac involved in plant-pathogen interactions.

PMID- 24676797
TI  - MANIA-a pattern classification toolbox for neuroimaging data.
AB  - Conventional univariate statistics are common and widespread in neuroimaging
      research. However, functional and structural MRI data reveal a multivariate
      nature, since neighboring voxels are highly correlated and different localized
      brain regions activate interdependently. Multivariate pattern classification
      techniques are capable of overcoming shortcomings of univariate statistics. A
      rising interest in such approaches on neuroimaging data leads to an increasing
      demand of appropriate software and tools in this field. Here, we introduce and
      release MANIA-Machine learning Application for NeuroImaging Analyses. MANIA is a
      Matlab based software toolbox enabling easy pattern classification of
      neuroimaging data and offering a broad assortment of machine learning algorithms
      and feature selection methods. Between groups classifications are the main scope
      of this software, for instance the differentiation between patients and controls.
      A special emphasis was placed on an intuitive and easy to use graphical user
      interface allowing quick implementation and guidance also for clinically oriented
      researchers. MANIA is free and open source, published under GPL3 license. This
      work will give an overview regarding the functionality and the modular software
      architecture as well as a comparison between other software packages.

PMID- 24676798
TI  - Disordered eating and health-related quality of life in overweight and obese
      children.
AB  - OBJECTIVES: To examine disordered eating and associations with health-related
      quality of life (HRQOL) in rural overweight/obese (OW/OB) children. METHODS:
      Cross-sectional analyses were conducted with 272 rural OW/OB children aged 8-12
      years (M = 10.36; SD = 1.39). Child anthropometrics, demographics, disordered
      eating attitudes, unhealthy weight control behaviors (UWCBs), and HRQOL were
      measured. Relationships between these variables were analyzed using bootstrapped
      multiple linear regressions. RESULTS: Clinically significant disordered eating
      attitudes were endorsed by 17% of the sample, and the majority endorsed UWCBs.
      Disordered eating attitudes and weight status were the most common predictors of
      HRQOL. Disordered eating attitudes and UWCBs were negatively related to emotional
      HRQOL but were unrelated to social, school, or physical HRQOL. CONCLUSIONS:
      Disordered eating is a serious and relevant problem in OW/OB children living in
      rural areas and may be indicative of impairments in emotional functioning. Early
      intervention may reduce the risk for eating disorders and associated negative
      sequelae.

PMID- 24676799
TI  - Sample size determination in group-sequential clinical trials with two co-primary
      endpoints.
AB  - We discuss sample size determination in group-sequential designs with two
      endpoints as co-primary. We derive the power and sample size within two decision
      making frameworks. One is to claim the test intervention's benefit relative to
      control when superiority is achieved for the two endpoints at the same interim
      timepoint of the trial. The other is when superiority is achieved for the two
      endpoints at any interim timepoint, not necessarily simultaneously. We evaluate
      the behaviors of sample size and power with varying design elements and provide a
      real example to illustrate the proposed sample size methods. In addition, we
      discuss sample size recalculation based on observed data and evaluate the impact
      on the power and Type I error rate.

PMID- 24676801
TI  - Intramuscular diffuse-type tenosynovial giant cell tumor of the deltoid muscle in
      a child.
AB  - Tenosynovial giant cell tumors (GCTs) typically form in the joints or extra
      articular soft tissues such as the tendon sheath, and are benign tumors that
      commonly occur in the hands or wrists in the third to fifth decades of life.
      However, the diffuse type of extra-articular GCT arising within muscle is a rare
      soft tissue tumor, especially in a pediatric patient. In this report, we describe
      the magnetic resonance imaging and sonographic findings of a rare case of
      intramuscular diffuse-type GCT in the deltoid muscle of a 9-year-old boy. 

PMID- 24676800
TI  - Overactive performance monitoring in obsessive-compulsive disorder is independent
      of symptom expression.
AB  - Overactive performance monitoring has been consistently reported in obsessive
      compulsive disorder (OCD). OCD is a clinically heterogeneous disorder and is
      characterized by several symptom dimensions that may have partially distinct
      neural correlates. We examined whether performance-monitoring alterations are
      related to symptom severity and symptom dimensions. Electrocortical correlates of
      performance monitoring were assessed in 72 OCD patients and 72 matched healthy
      comparison participants during a flanker task. Amplitudes of the error- and
      correct-related negativity as well as delta and theta power were used to quantify
      performance-monitoring activity, and a composite measure was derived using factor
      analysis. Symptom dimension scores were obtained from the Yale-Brown Obsessive
      Compulsive Scale symptom checklist. OCD patients showed increased electrocortical
      responses associated with correct and erroneous responses compared to healthy
      comparison participants. In patients, no correlations were obtained between
      performance monitoring and global symptom severity as well as lifetime symptom
      dimension scores. Only a statistical trend was found that higher
      symmetry/hoarding scores were associated with reduced performance-monitoring
      activity. For present symptom dimensions scores, an association with
      rituals/superstitious symptoms was obtained such that higher scores were
      associated with greater performance-monitoring activity. However, for both
      dimensions, subjects with low scores or high scores on each dimension were
      characterized by overactive performance monitoring compared to healthy controls.
      Overactive brain processes during performance monitoring are a neural correlate
      of OCD that is independent of global symptom severity and can be observed for all
      symptom dimensions. This supports the notion of overactive performance monitoring
      being a candidate endophenotype for OCD. 

PMID- 24676802
TI  - The cytoplasmic domain of rat synaptotagmin I enhances synaptic transmission.
AB  - Synaptotagmin, an integral membrane protein of synaptic vesicles, functions as a
      calcium sensor in the temporal control of neurotransmitter release. Although
      synaptotagmin facilitates lipid membrane fusion in biochemical experiments,
      overexpression of synaptotagmin inhibits neurotransmission. A facilitatory effect
      of synaptotagmin on synaptic transmission was never observed. To determine
      whether synaptotagmin may accelerate synaptic transmission in vivo, we injected
      the cytoplasmic domain of rat synaptotagmin I (CD-syt) into crayfish motor axons
      and tested the effect of CD-syt on synaptic response. We confirmed that CD-syt
      accelerates neuromuscular transmission. The injected preparation had larger
      synaptic potentials with shorter rise time. Experiments with varying calcium
      concentrations showed that CD-syt increased the maximum synaptic response of the
      neuromuscular synapses. Further tests on short-term plasticity of neuromuscular
      synapses revealed that CD-syt increases the release probability of the release
      ready vesicles. 

PMID- 24676803
TI  - Increased FoxM1 expression is a target for metformin in the suppression of EMT in
      prostate cancer.
AB  - Forkhead box M1 (FoxM1) transcription factor is related to the pathogenesis of
      various malignancies and recent evidence indicates that FoxM1 promotes epithelial
      mesenchymal transition (EMT) in breast cancer. Metformin can inhibit the
      progression of cancer. However, whether FoxM1 plays a role in EMT in prostate
      cancer (PCa) and whether metformin can suppress EMT through FoxM1 in PCa remain
      unresolved issues. In this study, we investigated the expression levels of the
      FoxM1 protein in 62 PCa and 39 benign prostate hyperplasia (BPH) samples and
      found that the expression levels of FoxM1 were higher in the PCa tissues (66.1%)
      compared with the BPH tissues (28.2%) (p<0.05). We observed that FoxM1 was
      expressed in the PCa cell lines and that metformin suppressed cell proliferation
      and the expression of FoxM1. We induced EMT in the PCa cells by the addition of
      transforming growth factor (TGF)-beta1 and verified the process by examining EMT
      related gene (E-cadherin, vimentin and Slug) expression. In addition, the
      knockdown of FoxM1 by shRNA in the PCa cells reversed EMT and markedly reduced
      cell migration. These results indicate that metformin suppresses EMT by
      inhibiting FoxM1. We demonstrate that the suppression of FoxM1 may be an
      effective therapeutic strategy for PCa and provide further evidence of the
      anticancer effects of metformin.

PMID- 24676804
TI  - Does post-infectious olfactory loss affect mood more severely than chronic
      sinusitis with olfactory loss?
AB  - OBJECTIVES/HYPOTHESIS: Olfactory deficits that develop after viral upper
      respiratory infection (URI) may have different effects on patient depression
      index compared to chronic sinusitis with olfactory loss. However, there have been
      no controlled trials to evaluate the different effects of chronic sinusitis and
      URI on depression index. STUDY DESIGN: Prospective study of 25 subjects in two
      groups. METHODS: This study enrolled 25 participants who were diagnosed with post
      URI olfactory loss as the study group and 25 patients with chronic sinusitis and
      olfactory loss as a control group. Control group participants were matched for
      age, sex, and degree of olfactory loss (threshold, discrimination, and
      identification [TDI]). We compared the Beck Depression Inventory (BDI) scores of
      each group and analyzed the correlation between TDI and BDI. RESULTS: The mean
      BDI score of the post-URI group was significantly higher than that of the control
      group (14.52 +/- 6.59 vs. 9.32 +/- 5.23; P=.002). Age, sex, and TDI score did not
      affect BDI score in the post-URI olfactory loss group. However, BDI score in the
      sinusitis group was inversely correlated with TDI score (R=-0.423; P=.035), and
      the BDI score of female subjects (11.00 +/- 5.13) was significantly higher than
      that of male subjects (5.00 +/- 2.16; P = .047). CONCLUSIONS: Post-URI olfactory
      loss affected patient mood more severely than chronic sinusitis with a similar
      degree of olfactory loss. This influence was not affected by sex, age, or TDI
      score in the post-URI olfactory loss group. LEVEL OF EVIDENCE: 3b.

PMID- 24676805
TI  - Direct crosstalk between cancer and osteoblast lineage cells fuels metastatic
      growth in bone via auto-amplification of IL-6 and RANKL signaling pathways.
AB  - The bone microenvironment and its modification by cancer and host cell
      interactions is a key driver of skeletal metastatic growth. Interleukin-6 (IL-6)
      stimulates receptor activator of NF-kappaB ligand (RANKL) expression in bone
      cells, and serum IL-6 levels are associated with poor clinical outcomes in cancer
      patients. We investigated the effects of RANKL on cancer cells and the role of
      tumor-derived IL-6 within the bone microenvironment. Using human breast cancer
      cell lines to induce tumors in the bone of immune-deficient mice, we first
      determined whether RANKL released by cells of the osteoblast lineage directly
      promotes IL-6 expression by cancer cells in vitro and in vivo. We then disrupted
      of IL-6 signaling in vivo either via knockdown of IL-6 in tumor cells or through
      treatment with specific anti-human or anti-mouse IL-6 receptor antibodies to
      investigate the tumor effect. Finally, we tested the effect of RANK knockdown in
      cancer cells on cancer growth. We demonstrate that osteoblast lineage-derived
      RANKL upregulates secretion of IL-6 by breast cancers in vivo and in vitro. IL-6,
      in turn, induces expression of RANK by cancer cells, which sensitizes the tumor
      to RANKL and significantly enhances cancer IL-6 release. Disruption in vivo of
      this auto-amplifying crosstalk by knockdown of IL-6 or RANK in cancer cells, or
      via treatment with anti-IL-6 receptor antibodies, significantly reduces tumor
      growth in bone but not in soft tissues. RANKL and IL-6 mediate direct paracrine
      autocrine signaling between cells of the osteoblast lineage and cancer cells,
      significantly enhancing the growth of metastatic breast cancers within bone.

PMID- 24676806
TI  - The expression of miR-30a* and miR-30e* is associated with a dualistic model for
      grading ovarian papillary serious carcinoma.
AB  - Histological grade has already been recognized as a very important prognostic
      factor for ovarian papillary serous carcinoma (OPSC). On the basis of
      pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC
      consisting of types I (low-grade) and II (high-grade) cancers. High-grade OPSC is
      responsible for most ovarian cancer deaths. The goal of our investigation was to
      identify the differences in key miRNAs and possible regulators through miRNA
      microarray chip analysis, as well as functional target prediction and clinical
      outcome between the low and high-grade OPSC patients. The pathogenic basis in
      differentiation of ovarian cancer subtypes was studied to provide insight into
      diagnosis and therapy for high-grade cases. Through microarray analysis, we found
      that miR-30a* and miR-30e* were the top 2 significantly different miRNAs between
      type I and type II OPSC patients, and both were remarkably downregulated in the
      latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a* and
      miR-30e*, and showed a significant upregulation in type II patients. As ATF3 and
      MYC are often associated with aggressive behavior and poor differentiation,
      especially in human cancers, these results are in good agreement with our
      findings and point toward a regulating differentiation function of the miR-30a*
      and miR-30e* genes. Further analysis using leave-one-out cross predictions and
      Kaplan-Meier survival analysis strongly suggested that miR-30a* and miR-30e* can
      be used as biomarkers to tailor histological grade before starting the regimen,
      and they showed important roles in ovarian cancer differentiation resulting in
      poorer prognosis. In general, miR-30a* and miR-30e* coupled with expression data
      that reveal pathogenic regulation to predict histological differentiation, may
      operate to direct the formation of early detection and therapeutic approaches to
      individual OPSC patients, especially differentiation therapy to high-grade cases.

PMID- 24676807
TI  - Estimating genome-wide significance for whole-genome sequencing studies.
AB  - Although a standard genome-wide significance level has been accepted for the
      testing of association between common genetic variants and disease, the era of
      whole-genome sequencing (WGS) requires a new threshold. The allele frequency
      spectrum of sequence-identified variants is very different from common variants,
      and the identified rare genetic variation is usually jointly analyzed in a series
      of genomic windows or regions. In nearby or overlapping windows, these test
      statistics will be correlated, and the degree of correlation is likely to depend
      on the choice of window size, overlap, and the test statistic. Furthermore,
      multiple analyses may be performed using different windows or test statistics.
      Here we propose an empirical approach for estimating genome-wide significance
      thresholds for data arising from WGS studies, and we demonstrate that the
      empirical threshold can be efficiently estimated by extrapolating from
      calculations performed on a small genomic region. Because analysis of WGS may
      need to be repeated with different choices of test statistics or windows, this
      prediction approach makes it computationally feasible to estimate genome-wide
      significance thresholds for different analysis choices. Based on UK10K whole
      genome sequence data, we derive genome-wide significance thresholds ranging
      between 2.5 * 10(-8) and 8 * 10(-8) for our analytic choices in window-based
      testing, and thresholds of 0.6 * 10(-8) -1.5 * 10(-8) for a combined analytic
      strategy of testing common variants using single-SNP tests together with rare
      variants analyzed with our sliding-window test strategy. 

PMID- 24676808
TI  - Characterization of the intramolecular transfer state of marine carotenoid
      fucoxanthin by femtosecond pump-probe spectroscopy.
AB  - Fucoxanthin, containing a carbonyl group in conjugation with its polyene
      backbone, is a naturally occurring pigment in marine organisms and is essential
      to the photosynthetic light-harvesting function in brown alga and diatom.
      Fucoxanthin exhibits optical characteristics attributed to an intramolecular
      charge transfer (ICT) state that arises in polar environments due to the presence
      of the carbonyl group. In this study, we report the spectroscopic properties of
      fucoxanthin in methanol (polar and protic solvent) observed by femtosecond pump
      probe measurements in the near-infrared region, where transient absorption
      associated with the optically allowed S2 (1(1)B u (+) ) state and stimulated
      emission from the strongly coupled S1/ICT state were observed following one
      photon excitation to the S2 state. The results showed that the amplitude of the
      stimulated emission of the S1/ICT state increased with decreasing excitation
      energy, demonstrating that the fucoxanthin form associated with the lower energy
      of the steady-state absorption exhibits stronger ICT character. 

PMID- 24676809
TI  - Two stents for simultaneous esophageal and gastric cancer.

PMID- 24676810
TI  - Successful endoscopic treatment for Mirizzi syndrome type II under direct peroral
      cholangioscopy using an ultraslim upper endoscope.

PMID- 24676811
TI  - Retrieval of a sharp foreign body from the stomach: a novel approach.

PMID- 24676812
TI  - Mucinous carcinoma of the eyelid with colonic mass: a rare partnership.

PMID- 24676813
TI  - Osteosarcoma metastasizing to pancreas confirmed by endoscopic ultrasound-guided
      fine-needle aspiration.

PMID- 24676814
TI  - Endoscopic incision plus esophageal stenting for refractory esophageal stricture
      in children.

PMID- 24676815
TI  - Successful treatment of a large choledochal inflammatory polyp in a patient with
      cutaneous neurofibromatosis.

PMID- 24676816
TI  - Endoscopic sclerotherapy with aluminum potassium sulfate and tannic acid for
      internal hemorrhoids.

PMID- 24676817
TI  - Endoscopic submucosal dissection of an esophageal tumor using a transnasal
      endoscope without sedation.

PMID- 24676818
TI  - Multiple infections with helminths--whipworm, hookworm, and roundworm.

PMID- 24676819
TI  - Gastric hamartomatous inverted polyp mimicking ectopic pancreas on endoscopy and
      endosonography.

PMID- 24676820
TI  - Colon sarcoidosis presenting with abdominal pain.

PMID- 24676821
TI  - Cardiac incidentaloma during endoscopic ultrasound: cardiac myxoma with Gamna
      Gandy bodies.

PMID- 24676822
TI  - Pseudoaneurysm eroding into the duodenal bulb: an extremely rare case and
      treatment modality.

PMID- 24676823
TI  - Mantle cell lymphoma of the colon.

PMID- 24676824
TI  - Late presentation of a giant gastrogastric fistula following gastric bypass,
      treated with a colic over-the-scope clip after unsuccessful surgical repair.

PMID- 24676825
TI  - Esophageal natural killer (NK)/T cell lymphoma of true natural killer cell
      origin.

PMID- 24676826
TI  - Peroral endoscopic myotomy (POEM) for diffuse esophageal spasm.

PMID- 24676827
TI  - Successful endoscopic treatment of Boerhaave syndrome using an over-the-scope
      clip.

PMID- 24676828
TI  - Endoscopic ultrasound-guided therapy of a rectal Dieulafoy lesion.

PMID- 24676829
TI  - Successful removal of a pancreatic duct stone in a patient with Whipple
      resection, using a short single-balloon enteroscope with a transparent hood.

PMID- 24676830
TI  - Efficient and safe esophageal endoscopic submucosal dissection using inverted
      overtube after changing patient position.

PMID- 24676831
TI  - Mesh erosion after vertical-banded gastroplasty.

PMID- 24676832
TI  - Fatal retroperitoneal gas gangrene complicating colonoscopic polypectomy without
      bowel perforation in a healthy adult.

PMID- 24676833
TI  - Transpapillary EUS-guided retrograde puncture of the biliary tree as an
      alternative for failed rendezvous procedure.

PMID- 24676834
TI  - Eosinophilic cholangitis diagnosed endoscopically.

PMID- 24676835
TI  - Olmesartan-induced enteropathy resembling celiac disease.

PMID- 24676836
TI  - Esophagitis dissecans superficialis due to severe methotrexate toxicity.

PMID- 24676837
TI  - Recent developments in the medical and surgical treatment of melanoma.
AB  - Increasing knowledge of the biology of melanoma has led to significant advances
      in drug development to fight this disease. Surgery is the primary treatment for
      localized disease and is an integral part of management in patients with more
      advanced disease. The last decade has become the era of targeted therapy in
      melanoma and has revolutionized the treatment of this disease. Since 2011, 4 new
      agents have been approved for the treatment of patients with metastatic melanoma:
      ipilimumab, vemurafenib, dabrafenib, and trametinib. Several new agents are
      currently in phase 3 trials with hopes of even more agents being approved for
      this once "untreatable" disease. How to integrate surgical options with more
      effective systemic therapies has become a new challenge for physicians. This
      review will provide an update on current surgical options, highlight the pathway
      to the development of the newly approved agents, and further discuss new
      treatments that are on the horizon.

PMID- 24676838
TI  - Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma.
AB  - The expression patterns of the Dickkopf (Dkk) family of proteins varies in
      different cancers. In the present study, the expression levels of Dkk1 and Dkk3
      were investigated in clear cell renal cell carcinoma (ccRCC) tissues. Dkk1 and
      Dkk3 serum levels were also examined in patients with ccRCC, and the association
      between clinicopathological features and Dkk levels was investigated. Serum Dkk1
      and Dkk3 were quantified using ELISA in 64 patients with ccRCC and in 30 healthy
      individuals (controls). The expression levels of Dkk1 and Dkk3 were analyzed in
      tumor and adjacent normal tissues obtained from patients with ccRCC (n=20) using
      quantitative polymerase chain reaction (qPCR), western blot analysis and
      immunohistochemistry. The mean serum levels of Dkk1 and Dkk3 in the patients with
      ccRCC were significantly lower than those in the healthy controls. Furthermore,
      the serum Dkk1 levels were significantly lower at higher tumor-node-metastasis
      stages and tumor grades. qPCR, western blot analysis and immunohistochemistry
      revealed a significant decrease in the Dkk1 and Dkk3 mRNA and protein levels in
      the tumor tissues compared with the adjacent normal tissues. Consequently, Dkk1
      and Dkk3 may present a novel molecular target for the diagnosis and therapeutic
      treatment of ccRCC.

PMID- 24676839
TI  - Analyzing the electric response of molecular conductors using "electron
      deformation" orbitals and occupied-virtual electron transfer.
AB  - The concept of "electron deformation orbitals" (EDOs) is used to investigate the
      electric response of conducting metals and oligophenyl chains. These orbitals and
      their eigenvalues are obtained by diagonalization of the deformation density
      matrix (difference between the density matrices of the perturbed and unperturbed
      systems) and can be constructed as linear combinations of the unperturbed
      molecular orbitals within "frozen geometry" conditions. This form of the EDOs
      allows calculating the part of the electron deformation density associated to an
      effective electron transfer from occupied to virtual orbitals (valence to
      conduction band electron transfer in the band model of conductivity). It is found
      that the "electron deformation" orbitals pair off, displaying the same eigenvalue
      but opposite sign. Each pair represents an amount of accumulation/depletion of
      electron charge at different molecular regions. In the oligophenyl systems
      investigated only one pair contributes effectively to the charge flow between
      molecular ends, resulting from the promotion of electrons from occupied orbitals
      to close in energy virtual orbitals of appropriate symmetry and overlapping.
      Analysis of this pair along explains the differences in conductance of
      olygophenyl chains based on phenyl units.

PMID- 24676841
TI  - Joint modeling of two longitudinal outcomes and competing risk data.
AB  - Aortic gradient and aortic regurgitation are echocardiographic markers of aortic
      valve function. Both are biomarkers repeatedly measured in patients with valve
      abnormalities, and thus, it is expected that they are biologically interrelated.
      Loss of follow-up could be caused by multiple reasons, including valve
      progression related, such as an intervention or even the death of the patient. In
      that case, it would be of interest and appropriate to analyze these outcomes
      jointly. Joint models have recently received much attention because they cover a
      wide range of clinical applications and have promising results. We propose a
      joint model consisting of two longitudinal outcomes, one continuous (aortic
      gradient) and one ordinal (aortic regurgitation), and two time-to-events (death
      and reoperation). Moreover, we allow for more flexibility for the average
      evolution and the subject-specific profiles of the continuous repeated outcome by
      using B-splines. A disadvantage, however, is that when adopting a non-linear
      structure for the model, we may have difficulties when interpreting the results.
      To overcome this problem, we propose a graphical approach. In this paper, we
      apply the proposed joint models under the Bayesian framework, using a data set
      including serial echocardiographic measurements of aortic gradient and aortic
      regurgitation and measurements of the occurrence of death and reoperation in
      patients who received a human tissue valve in the aortic position. The
      interpretation of the results will be discussed.

PMID- 24676840
TI  - Opposing effects of HIF1alpha and HIF2alpha on chromaffin cell phenotypic
      features and tumor cell proliferation: Insights from MYC-associated factor X.
AB  - Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing
      chromaffin cell tumors with diverse phenotypic features reflecting mutations in
      numerous genes, including MYC-associated factor X (MAX). To explore whether
      phenotypic differences among PPGLs reflect a MAX-mediated mechanism and opposing
      influences of hypoxia-inducible factor (HIF)s HIF2alpha and HIF1alpha, we
      combined observational investigations in PPGLs and gene-manipulation studies in
      two pheochromocytoma cell lines. Among PPGLs from 140 patients, tumors due to MAX
      mutations were characterized by gene expression profiles and intermediate
      phenotypic features that distinguished these tumors from other PPGLs, all of
      which fell into two expression clusters: one cluster with low expression of
      HIF2alpha and mature phenotypic features and the other with high expression of
      HIF2alpha and immature phenotypic features due to mutations stabilizing HIFs. Max
      mutated tumors distributed to a distinct subcluster of the former group. In cell
      lines lacking Max, re-expression of the gene resulted in maturation of phenotypic
      features and decreased cell cycle progression. In cell lines lacking Hif2alpha,
      overexpression of the gene led to immature phenotypic features, failure of
      dexamethasone to induce differentiation and increased proliferation. HIF1alpha
      had opposing actions to HIF2alpha in both cell lines, supporting evolving
      evidence of their differential actions on tumorigenic processes via a MYC/MAX
      related pathway. Requirement of a fully functional MYC/MAX complex to facilitate
      differentiation explains the intermediate phenotypic features in tumors due to
      MAX mutations. Overexpression of HIF2alpha in chromaffin cell tumors due to
      mutations affecting HIF stabilization explains their proliferative features and
      why the tumors fail to differentiate even when exposed locally to adrenal
      steroids. 

PMID- 24676842
TI  - Rectovaginal fistula: a new technique and preliminary results using collagen
      matrix biomesh.
AB  - BACKGROUND: A rectovaginal fistula (RVF) is a debilitating condition that is
      difficult to treat. Many available techniques are invasive and involve extensive
      surgery. A local procedure with good closure rates would be preferable as a first
      step in the treatment of RVF. The aim of this study was the development of a
      local technique for the closure of RVF with good closure rates to prevent the use
      of more invasive procedures. METHODS: This was a pilot study. Patients with RVF
      who had undergone multiple operations in the pelvic area, local radiotherapy,
      chemotherapy or had been diagnosed with Crohn's disease were included in the
      study. All had a history of surgery for RVF. A cross-linked collagen matrix
      biomesh was placed in the rectovaginal septum using a transperineal or a
      transvaginal approach. The main outcome measure in this study was the closure
      rate reported as absence of the fistula at 1 year. RESULTS: Twelve patients were
      included in the study. Absence of fistula at 1 year was 0.64 (95 % confidence
      interval 0.30-0.85). Three patients (25.0 %) developed a recurrence, two were
      reoperated on with a gracilis flap transposition, and one was treated with
      laparoscopic ligation. In one patient (8.3 %), the fistula failed to close within
      3 months after the mesh placement. CONCLUSIONS: Our technique shows promising
      results. A local and simple technique with acceptable closure and morbidity
      rates, like our local repair with biomesh, would be ideal as a first step in
      treating RVFs. Long-term results are needed.

PMID- 24676843
TI  - Bone mineral density and bone turnover in non-cirrhotic patients with chronic
      hepatitis C and sustained virological response to antiviral therapy with
      peginterferon-alfa and ribavirin.
AB  - Patients with chronic hepatitis C have low bone mineral density and increased
      bone resorption related to serum transaminase levels. Elevated serum soluble
      tumor necrosis factor (sTNFR-55) receptor levels may play a role in the bone mass
      loss in these patients. Bone mass is improved and bone turnover normalized in
      patients who respond to antiviral therapy with interferon and ribavirin.
      INTRODUCTION: Low bone mineral density (BMD) has been described in patients with
      chronic hepatitis C (HCV). The study objective was to evaluate the effect of
      antiviral therapy on BMD and bone metabolism in non-cirrhotic HCV patients with
      sustained virological response. METHODS: We conducted a prospective study in 36
      consecutive outpatients from the general community with non-cirrhotic HCV and an
      early and sustained virological response to peginterferon-alfa and ribavirin
      therapy. Determinations of BMD (dual X-ray absorptiometry at lumbar spine and
      femoral neck) and biochemical measurements of bone metabolism and sTNFR-55 were
      made at baseline, after 24 and 48 weeks of antiviral therapy, and at 48 weeks
      after the end of treatment. RESULTS: Patients had a significantly reduced BMD,
      which significantly increased during the follow-up. Serum levels of sTNFR-55 and
      bone turnover markers were increased at baseline and significantly reduced at all
      subsequent time points. We found an inverse correlation between BMD and both
      serum aminotransferase levels and urine deoxypyridinoline (D-pyr) and a positive
      correlation between serum aminotransferases and both urine D-Pyr and serum sTNFR
      55. CONCLUSIONS: Patients with chronic hepatitis C have low bone mass associated
      with increased bone resorption, and some relationship can be expected between
      serum aminotransferase levels and the degree of bone mass loss. Bone mass may be
      improved and bone turnover normalized in patients who respond to antiviral
      therapy. Elevated serum sTRFR-55 levels may play a role in the bone mass loss of
      these patients.

PMID- 24676844
TI  - Biochemical markers of bone turnover in diabetes patients--a meta-analysis, and a
      methodological study on the effects of glucose on bone markers.
AB  - This study examined whether markers of bone turnover differ between individuals
      with and without diabetes. Bone markers showed heterogeneity between studies and
      were discrepant for markers of bone creation and markers of bone degradation.
      Bone markers may be of lesser value in diabetes due to heterogeneity.
      INTRODUCTION: The aim of this meta-analysis was to compare existing literature
      regarding changes in bone markers among diabetics compared to healthy controls.
      To exclude that blood glucose levels among diabetes patients could influence the
      assays used for determining bone turnover markers, a methodological study was
      performed. METHODS: Medline at Pubmed Embase, Cinahl, Svemed+, Cochrane library,
      and Bibliotek.dk was searched in August 2012. The studies should examine
      biochemical bone turnover among diabetes patients in comparison to controls in an
      observational design. In the methodological study, fasting blood samples were
      drawn from two individuals. Glucose was added to the blood samples in different
      concentrations and OC, CTX, and procollagen type 1 amino terminal propeptide were
      measured after 0, 1, 2, and 3 h. RESULTS: Twenty-two papers fulfilled the
      criteria for the meta-analysis. From the pooled data in the meta-analysis, the
      bone markers osteocalcin (OC) (-1.15 ng/ml [-1.78,-0.52]) and C-terminal cross
      linked telopeptide (CTX) (-0.14 ng/ml [-0.22, -0.05]) were significantly lower
      among diabetes patients than non-diabetes patients, however other markers did not
      differ. All markers displayed very high heterogeneity by I2 statistics. In the
      methodological study, the addition of glucose did not significantly change the
      bone markers neither by level of glucose nor with increasing incubation time.
      CONCLUSION: The dissociative pattern of biochemical bone markers of bone
      formation and bone resorption present in diabetes patients is thus not caused by
      glucose per se but may be modulated by unknown factors associated with diabetes
      mellitus.

PMID- 24676845
TI  - The impact of common co-morbidities (as measured using the Charlson index) on hip
      fracture risk in elderly men: a population-based cohort study.
AB  - We used a large population-based health care database to determine the impact of
      common co-morbidities on hip fracture risk amongst elderly men. We demonstrated
      that diabetes, chronic obstructive pulmonary disease, renal failure, HIV
      infection, dementia, and cerebrovascular disease are independent predictors of
      hip fracture, as is a Charlson score of >= 3. INTRODUCTION: Risk factors for hip
      fractures in men are still unclear. We aimed to identify common co-morbidities
      (amongst those in the Charlson index) that confer an increased risk of hip
      fracture amongst elderly men. METHODS: We conducted a population-based cohort
      study using data from the SIDIAP (Q) database. SIDIAP(Q) contains primary care
      and hospital inpatient records of a representative 30% of the population of
      Catalonia, Spain (>2 million people). All men aged >= 65 years registered on 1
      January 2007 were followed up until 31 December 2009. Both exposure (co
      morbidities in the Charlson index) and outcome (incident hip fractures) were
      ascertained using ICD codes. Poisson regression models were fitted to estimate
      the effect of (1) each individual co-morbidity and (2) the composite Charlson
      index score, on hip fracture risk, after adjustment for age, body mass index,
      smoking, alcohol drinking, and use of oral glucocorticoids. RESULTS: We observed
      186,171 men for a median (inter-quartile range) of 2.99 (2.37-2.99) years. In
      this time, 1,718 (0.92%) participants had a hip fracture. The following co
      morbidities were independently associated with hip fractures: diabetes mellitus,
      chronic obstructive pulmonary disease (COPD), renal failure, HIV infection,
      dementia, and cerebrovascular disease. A Charlson score of >= 3 conferred an
      increased hip fracture risk. CONCLUSION: Common co-morbidities including
      diabetes, COPD, cerebrovascular disease, renal failure, and HIV infection are
      independently associated with an increased risk of hip fracture in elderly men. A
      Charlson score of 3 or more is associated with a 50% higher risk of hip fracture
      in this population.

PMID- 24676846
TI  - Individual site-specific bone mineral density gain in normocalcemic primary
      hyperparathyroidism.
AB  - In this study, we show that successful parathyroidectomy is followed at 1 year by
      a significant individual bone mineral density (BMD) gain in nearly half of
      normocalcemic PHPT patients with reduced bone mass. Alkaline phosphatase levels
      above median were identified as an independent predictor of individual BMD gain
      in normocalcemic PHPT patients. INTRODUCTION: The aims of this study were to
      assess bone mineral density (BMD) gains after parathyroidectomy (PTX) in
      normocalcemic primary hyperparathyroidism (PHPT) at the individual level and to
      identify predictors of BMD gain after PTX in this context. METHODS: Longitudinal
      cohort study of 55 PHPT patients referred for low bone mass and mild
      abnormalities of calcium/phosphorus metabolism, and successfully treated by PTX.
      BMD gain at 1 year was considered significant if >=0.030 g/cm(2) at one site or
      more, without any equivalent BMD loss at another site. A logistic regression
      analysis was performed to identify predictive factors of individual BMD gain.
      RESULTS: Among the 55 PHPT patients included, 29 patients with hypercalcemia, 36
      patients with normocalcemic PHPT, defined by normal pre-PTX serum total (albumin
      corrected) calcium (tCa), including 15 patients with normal ionized calcium
      (iCa), were identified. At 1 year of PTX, an individual BMD gain was observed in
      73.7 % of hypercalcemic, 44.4 % of normocalcemic, and 46 % of PHPT patients with
      both normal tCa and iCa. Site-specific BMD gains were most important at the spine
      and hip in all subgroups including patients with normal iCa. Alkaline phosphatase
      activity above median, which reflects high bone turnover, was predictive of
      individual BMD gain, both in the overall cohort (OR = 4.9, 95 % CI 1.3-18.9), and
      in the normocalcemic group: OR = 8.4, 95 % CI 1.4-56.6. CONCLUSIONS: Successful
      PTX is followed at 1 year by a significant individual BMD gain in nearly half of
      normocalcemic PHPT patients with osteoporosis. ALP levels above median could
      contribute to the therapeutic decision in this context.

PMID- 24676847
TI  - Denosumab significantly increases bone mineral density and reduces bone turnover
      compared with monthly oral ibandronate and risedronate in postmenopausal women
      who remained at higher risk for fracture despite previous suboptimal treatment
      with an oral bisphosphonate.
AB  - Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is
      difficult. Such patients who remained at higher risk for fracture (>=1 risk
      factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated
      subjects had significantly greater increases in bone mineral density and
      decreases in bone turnover in this 12-month study. INTRODUCTION: A clinical need
      exists to manage patients who are suboptimally adherent to oral BPs and remain at
      higher risk for fracture. Here, we compare the effects on bone mineral density
      (BMD) and bone turnover of transitioning such patients to denosumab or monthly
      oral BP (ibandronate or risedronate). METHODS: In two previous multicenter, open
      label studies, postmenopausal women >=55 years previously treated with, though
      suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg
      subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for
      12 months. In this combined post-hoc analysis, a subset of higher risk subjects
      was identified, and the percentage changes from baseline in BMD and serum C
      telopeptide of type I collagen (sCTX-1) were assessed. RESULTS: In the overall
      population, denosumab was associated with greater gains in BMD at 12 months than
      monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for
      all). In higher risk subjects, denosumab led to greater gains in BMD than oral
      BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar
      spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater
      decreases in sCTX-1 in the overall population and higher risk subjects at months
      1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were
      generally similar between treatment groups. CONCLUSIONS: Transitioning to
      denosumab was well tolerated and more effective in increasing BMD and reducing
      bone turnover than cycling to a monthly oral BP treatment in subjects who
      remained at higher fracture risk despite suboptimal BP treatment.

PMID- 24676848
TI  - Effects of 18-month low-magnitude high-frequency vibration on fall rate and
      fracture risks in 710 community elderly--a cluster-randomized controlled trial.
AB  - This study is a prospective cluster-randomized controlled clinical trial
      involving 710 elderly subjects to investigate the long-term effects of low
      magnitude high-frequency vibration (LMHFV) on fall and fracture rates, muscle
      performance, and bone quality. The results confirmed that LMHFV is effective in
      reducing fall incidence and enhancing muscle performance in the elderly.
      INTRODUCTION: Falls are direct causes of fragility fracture in the elderly. LMHFV
      has been shown to improve muscle function and bone quality. This study is to
      investigate the efficacy of LMHFV in preventing fall and fractures among the
      elderly in the community. METHODS: A cluster-randomized controlled trial was
      conducted with 710 postmenopausal females over 60 years. A total of 364
      participants received daily 20 min LMHFV (35 Hz, 0.3 g), 5 days/week for 18
      months; 346 participants served as control. Fall or fracture rate was taken as
      the primary outcome. Also, quadriceps muscle strength, balancing abilities, bone
      mineral density (BMD), and quality of life (QoL) assessments were done at 0, 9,
      and 18 months. RESULTS: With an average of 66.0% compliance in the vibration
      group, 18.6% of 334 vibration group subjects reported fall or fracture incidences
      compared with 28.7% of 327 in the control (adjusted HR = 0.56, p = 0.001). The
      fracture rate of vibration and control groups were 1.1 and 2.3 % respectively (p
      = 0.171). Significant improvements were found in reaction time, movement
      velocity, and maximum excursion of balancing ability assessment, and also the
      quadriceps muscle strength (p < 0.001). No significant differences were found in
      the overall change of BMD. Minimal adverse effects were documented. CONCLUSION:
      LMHFV is effective in fall prevention with improved muscle strength and balancing
      ability in the elderly. We recommend its use in the community as an effective
      fall prevention program and to decrease related injuries.

PMID- 24676849
TI  - A comparison of the mandibular index on panoramic and cross-sectional images from
      CBCT exams from osteoporosis risk group.
AB  - Osteoporosis is a degenerative disease that primarily affects postmenopausal
      women. Based on panoramic radiographs, several assessment methods have been
      proposed for the diagnosis and evaluation of bone changes and as a predictor of
      osteoporosis for example the mandibular index. INTRODUCTION: The purpose of this
      study is to compare the assessment of mandibular indices on panoramic and cross
      sectional images. METHODS: Forty-four cone beam computed tomography (CBCT) images
      from postmenopausal female subjects aged more than 45 years without systemic
      changes were selected for this study. From those images, cross-sectional and
      panoramic reconstruction images were assembled into a template for evaluation.
      The evaluation was conducted by observing the panoramic images and parasagittal
      sections. The appearance of the inferior cortex of the mandible was classified
      according to the mandibular index: C1, the endosteal margin of the cortex was
      even and sharp; C2, the endosteal margin presented semilunar defects or appeared
      to form endosteal cortical residues; or C3, the cortical layer formed heavy
      endosteal cortical residues and was clearly porous. RESULTS: Based on Wilcoxon
      statistical test (p > 0.01), the data showed no statistically significant
      difference between the exams. CONCLUSION: The mandibular index assigned in
      tomographic images is comparable to that obtained in panoramic images, indicating
      a valid use of the index in CBCT images, which can lead to the identification of
      patients with bone mass loss and a premature referral to further exams and
      treatment.

PMID- 24676850
TI  - A revaluation of the cultural dimension of disability policy in the European
      Union: the impact of digitization and web accessibility.
AB  - Reflecting the commitments undertaken by the EU through the conclusion of the
      United Nations Convention on the Rights of Persons with Disabilities (UNCRPD),
      the European Disability Strategy 2010-2020 not only gives a prominent position to
      accessibility, broadly interpreted, but also suggests an examination of the
      obligations for access to cultural goods and services. The European Disability
      Strategy 2010-2020 expressly acknowledges that EU action will support national
      activities to make sports, leisure, cultural and recreational organizations and
      activities accessible, and use the possibilities for copyright exceptions in the
      Directive 2001/29/EC (Infosoc Directive). This article discusses to what extent
      the EU has realized the principle of accessibility and the right to access
      cultural goods and services envisaged in the UNCRPD. Previous research has yet to
      explore how web accessibility and digitization interact with the cultural
      dimension of disability policy in the European Union. This examination attempts
      to fill this gap by discussing to what extent the European Union has put this
      cultural dimension into effect and how web accessibility policies and the
      digitization of cultural materials influence these efforts.

PMID- 24676851
TI  - Disparities of cancer incidence in Michigan's American Indians: spotlight on
      breast cancer.
AB  - BACKGROUND: In American Indians (AIs), cancer is a leading cause of mortality,
      yet their disease burden is not fully understood due to unaddressed racial
      misclassification in cancer registries. This study describes cancer trends among
      AIs in Michigan, focusing on breast cancer, in a linked data set of Indian Health
      Service (IHS), tribal, and state cancer registry data adjusted for
      misclassification. METHODS: AI status was based on reported race and linkage to
      IHS data and tribal registries. Data with complete linkage on all incident cancer
      cases in Michigan from 1995 to 2004 was used to calculate age-standardized
      incidence estimates for invasive all-site and female breast cancers stratified by
      racial group. For female breast cancers, stage- and age-specific incidence and
      percent distributions of early- versus late-stage cancers and age of diagnosis
      were calculated. RESULTS: More than 50% of all AI cases were identified through
      IHS and/or tribal linkage. In the linked data, AIs had the lowest rates of all
      sites and breast cancer. For breast cancers, AI women had a greater late-stage
      cancer burden and a younger mean age of diagnosis as compared to whites. Although
      the age-specific rate for whites was greater than for AI women in nearly all age
      groups, the difference in hazard ratio increased with increasing age.
      CONCLUSIONS: Our state-specific information will help formulate effective,
      tailored cancer prevention strategies to this population in Michigan. The data
      linkages used in our study are crucial for generating accurate rates and can be
      effective in addressing misclassification of the AI population and formulating
      cancer prevention strategies for AI nationwide.

PMID- 24676852
TI  - Proportional lumbar spine inter-vertebral motion patterns: a comparison of
      patients with chronic, non-specific low back pain and healthy controls.
AB  - INTRODUCTION: Identifying biomechanical subgroups in chronic, non-specific low
      back pain (CNSLBP) populations from inter-vertebral displacements has proven
      elusive. Quantitative fluoroscopy (QF) has excellent repeatability and provides
      continuous standardised inter-vertebral kinematic data from fluoroscopic
      sequences allowing assessment of mid-range motion. The aim of this study was to
      determine whether proportional continuous IV rotational patterns were different
      in patients and controls. A secondary aim was to update the repeatability of QF
      measurement of range of motion (RoM) for inter-vertebral (IV) rotation. METHODS
      AND MATERIALS: Fluoroscopic sequences were recorded of passive, recumbent coronal
      and sagittal motion, which was controlled for range and velocity. Segments L2-5
      in 40 primary care CNSLBP patients and 40 matched controls were compared.
      Patients also completed the von Korff Chronic Pain Grade and Roland and Morris
      Disability Questionnaire. Sequences were processed using automated image tracking
      algorithms to extract continuous inter-vertebral rotation data. These were
      converted to continuous proportional ranges of rotation (PR). The continuous
      proportional range variances were calculated for each direction and combined to
      produce a single variable representing their fluctuation (CPRV). Inter- and intra
      rater repeatability were also calculated for the maximum IV-RoM measurements
      obtained during controlled trunk motion to provide an updated indication of the
      reliability and agreement of QF for measuring spine kinematics. RESULTS: CPRV was
      significantly higher in patients (0.011 vs. 0.008, Mann-Whitney two-sided p =
      0.008), implying a mechanical subgroup. Receiver operating characteristic curve
      analysis found its sensitivity and specificity to be 0.78 % (60-90) and 0.55 %
      (37-73), respectively (area under the curve 0.672). CPRV was not correlated with
      pain severity or disability. The repeatability of maximum inter-vertebral range
      was excellent, but range was only significantly greater in patients at L4-5 in
      right side bending (p = 0.03). CONCLUSION: The variation in proportional motion
      between lumbar vertebrae during passive recumbent trunk motion was greater in
      patients with CNSLBP than in matched healthy controls, indicating that
      biomechanical factors in passive structures play a part.

PMID- 24676853
TI  - The change of whole lumbar segmental motion according to the mobility of
      degenerated disc in the lower lumbar spine: a kinetic MRI study.
AB  - PURPOSE: To analyze the effects of mobility of degenerated disc in the lower
      lumbar discs (L4-5 and L5-S1) on both whole lumbar motion and adjacent segment
      ROM. METHODS: The kMRIs with disc degeneration at L4-5 or L5-S1 were classified
      into three groups: the normal group, the motion-preserved (MP) group and the
      motion-lost (ML) group based on range of motion (ROM) of 5 degrees  in the
      degenerated segment. Each segmental ROM, whole lumbar motion, and the
      contribution % of the upper lumbar spine (ULS: L1-2-3) and the lower lumbar spine
      (LLS: L4-5-S1) motion to whole lumbar motion were measured and compared with each
      of the other groups. RESULTS: There were 94, 99 and 66 patients in the normal
      group, MP group and ML group, respectively. The normal group showed no
      significant difference compared to the MP group in all ROM parameters. The ML
      group showed significantly less whole lumbar motion, more contribution % in the
      ULS and less in the LLS than the normal and the MP groups. The ROM in the
      superior adjacent segment in the ML group was not significantly different between
      that in the normal and MP group. CONCLUSIONS: Degenerated lumbar discs did not
      show hypermobility within functional ROM. Loss of segmental ROM from advanced
      disc degeneration did not cause an increase in the ROM of the superior adjacent
      segment in vivo. When the LLS had motion-lost, advanced disc degeneration, whole
      lumbar motion was significantly decreased and compensatory increase in ROM was
      accomplished by the ULS.

PMID- 24676854
TI  - "Shaken baby syndrome" and forensic pathology.

PMID- 24676855
TI  - Abscisic acid uridine diphosphate glucosyltransferases play a crucial role in
      abscisic acid homeostasis in Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) is crucial for plant growth and adaptive
      responses to various stress conditions. Plants continuously adjust the ABA level
      to meet physiological needs, but how ABA homeostasis occurs is not fully
      understood. This study provides evidence that UGT71B6, an ABA uridine diphosphate
      glucosyltransferase (UGT), and its two closely related homologs, UGT71B7 and
      UGT71B8, play crucial roles in ABA homeostasis and in adaptation to dehydration,
      osmotic stress, and high-salinity stresses in Arabidopsis (Arabidopsis thaliana).
      UGT RNA interference plants that had low levels of these three UGT transcripts
      displayed hypersensitivity to exogenous ABA and high-salt conditions during
      germination and exhibited a defect in plant growth. However, the ectopic
      expression of UGT71B6 in the atbg1 (for beta-glucosidase) mutant background
      aggravated the ABA-deficient phenotype of atbg1 mutant plants. In addition,
      modulation of the expression of the three UGTs affects the expression of CYP707A1
      to CYP707A4, which encode ABA 8'-hydroxylases; four CYP707As were expressed at
      higher levels in the UGT RNA interference plants but at lower levels in the
      UGT71B6:GFP-overexpressing plants. Based on these data, this study proposes that
      UGT71B6 and its two homologs play a critical role in ABA homeostasis by
      converting active ABA to an inactive form (abscisic acid-glucose ester) depending
      on intrinsic cellular and environmental conditions in plants. 

PMID- 24676856
TI  - Plastid osmotic stress activates cellular stress responses in Arabidopsis.
AB  - Little is known about cytoplasmic osmoregulatory mechanisms in plants, and even
      less is understood about how the osmotic properties of the cytoplasm and
      organelles are coordinately regulated. We have previously shown that Arabidopsis
      (Arabidopsis thaliana) plants lacking functional versions of the plastid
      localized mechanosensitive ion channels Mechanosensitive Channel of Small
      Conductance-Like2 (MSL2) and MSL3 contain leaf epidermal plastids under
      hypoosmotic stress, even during normal growth and development. Here, we use the
      msl2 msl3 mutant as a model to investigate the cellular response to constitutive
      plastid osmotic stress. Under unstressed conditions, msl2 msl3 seedlings
      exhibited several hallmarks of drought or environmental osmotic stress, including
      solute accumulation, elevated levels of the compatible osmolyte proline (Pro),
      and accumulation of the stress hormone abscisic acid (ABA). Furthermore, msl2
      msl3 mutants expressed Pro and ABA metabolism genes in a pattern normally seen
      under drought or osmotic stress. Pro accumulation in the msl2 msl3 mutant was
      suppressed by conditions that reduce plastid osmotic stress or inhibition of ABA
      biosynthesis. Finally, treatment of unstressed msl2 msl3 plants with exogenous
      ABA elicited a much greater Pro accumulation response than in the wild type,
      similar to that observed in plants under drought or osmotic stress. These results
      suggest that osmotic imbalance across the plastid envelope can elicit a response
      similar to that elicited by osmotic imbalance across the plasma membrane and
      provide evidence for the integration of the osmotic state of an organelle into
      that of the cell in which it resides. 

PMID- 24676857
TI  - Non-cell-autonomous regulation of root hair patterning genes by WRKY75 in
      Arabidopsis.
AB  - In Arabidopsis (Arabidopsis thaliana), root hairs are formed in cell files over
      the cleft of underlying cortex cells. This pattern is established by a well-known
      gene regulatory network of transcription factors. In this study, we show that
      WRKY75 suppresses root hair development in nonroot hair files and that it
      represses the expression of TRIPTYCHON and CAPRICE. The WRKY75 protein binds to
      the CAPRICE promoter in a yeast one-hybrid assay. Binding to the promoter
      fragment requires an intact WRKY protein-binding motif, the W box. A comparison
      of the spatial expression of WRKY75 and the localization of the WRKY75 protein
      revealed that WRKY75 is expressed in the pericycle and vascular tissue and that
      the WRKY75 RNA or protein moves into the epidermis. 

PMID- 24676859
TI  - Evolutionary convergence of cell-specific gene expression in independent lineages
      of C4 grasses.
AB  - Leaves of almost all C4 lineages separate the reactions of photosynthesis into
      the mesophyll (M) and bundle sheath (BS). The extent to which messenger RNA
      profiles of M and BS cells from independent C4 lineages resemble each other is
      not known. To address this, we conducted deep sequencing of RNA isolated from the
      M and BS of Setaria viridis and compared these data with publicly available
      information from maize (Zea mays). This revealed a high correlation (r=0.89)
      between the relative abundance of transcripts encoding proteins of the core C4
      pathway in M and BS cells in these species, indicating significant convergence in
      transcript accumulation in these evolutionarily independent C4 lineages. We also
      found that the vast majority of genes encoding proteins of the C4 cycle in S.
      viridis are syntenic to homologs used by maize. In both lineages, 122 and 212
      homologous transcription factors were preferentially expressed in the M and BS,
      respectively. Sixteen shared regulators of chloroplast biogenesis were
      identified, 14 of which were syntenic homologs in maize and S. viridis. In
      sorghum (Sorghum bicolor), a third C4 grass, we found that 82% of these trans
      factors were also differentially expressed in either M or BS cells. Taken
      together, these data provide, to our knowledge, the first quantification of
      convergence in transcript abundance in the M and BS cells from independent
      lineages of C4 grasses. Furthermore, the repeated recruitment of syntenic
      homologs from large gene families strongly implies that parallel evolution of
      both structural genes and trans-factors underpins the polyphyletic evolution of
      this highly complex trait in the monocotyledons.

PMID- 24676858
TI  - The heat shock factor A4A confers salt tolerance and is regulated by oxidative
      stress and the mitogen-activated protein kinases MPK3 and MPK6.
AB  - Heat shock factors (HSFs) are principal regulators of plant responses to several
      abiotic stresses. Here, we show that estradiol-dependent induction of HSFA4A
      confers enhanced tolerance to salt and oxidative agents, whereas inactivation of
      HSFA4A results in hypersensitivity to salt stress in Arabidopsis (Arabidopsis
      thaliana). Estradiol induction of HSFA4A in transgenic plants decreases, while
      the knockout hsfa4a mutation elevates hydrogen peroxide accumulation and lipid
      peroxidation. Overexpression of HSFA4A alters the transcription of a large set of
      genes regulated by oxidative stress. In yeast (Saccharomyces cerevisiae) two
      hybrid and bimolecular fluorescence complementation assays, HSFA4A shows
      homomeric interaction, which is reduced by alanine replacement of three conserved
      cysteine residues. HSFA4A interacts with mitogen-activated protein kinases MPK3
      and MPK6 in yeast and plant cells. MPK3 and MPK6 phosphorylate HSFA4A in vitro on
      three distinct sites, serine-309 being the major phosphorylation site. Activation
      of the MPK3 and MPK6 mitogen-activated protein kinase pathway led to the
      transcriptional activation of the HEAT SHOCK PROTEIN17.6A gene. In agreement that
      mutation of serine-309 to alanine strongly diminished phosphorylation of HSFA4A,
      it also strongly reduced the transcriptional activation of HEAT SHOCK
      PROTEIN17.6A. These data suggest that HSFA4A is a substrate of the MPK3/MPK6
      signaling and that it regulates stress responses in Arabidopsis.

PMID- 24676860
TI  - Hormone replacement therapy and oral contraceptives and risk of oesophageal
      adenocarcinoma: a systematic review and meta-analysis.
AB  - There is an unexplained strong male predominance in the aetiology of oesophageal
      adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves
      attention. A potential protective influence of exogenous oestrogen exposure, that
      is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been
      addressed only in studies of limited statistical power, and the individual
      studies have not provided conclusive results. We conducted a systematic
      literature search and meta-analysis on HRT and OC and the risk of OAC. We used
      the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated by the Mantel-Haenszel random-effect method. A
      total of five studies were included. Compared to never users, ever users of HRT
      had a statistically significantly decreased risk of OAC (pooled OR = 0.75; 95%
      CI: 0.58-0.98), and ever users of OC had a borderline significantly decreased
      risk of this cancer (pooled OR = 0.76; 95% CI: 0.57-1.00). In conclusion, HRT and
      OC use seems to be associated with a decreased risk of OAC. However, further
      research is warranted. 

PMID- 24676861
TI  - Impacts of body mass index, physical activity, and smoking on femoral bone loss:
      the Tromso study.
AB  - Bone mineral density (BMD) is a reflection of bone strength and lifestyles that
      preserve bone mass and may reduce fracture risk in old age. This study examined
      the effect of combined profiles of smoking, physical activity, and body mass
      index (BMI) on lifetime bone loss. Data were collected from the population-based
      Tromso Study. BMD was measured as g/cm(2) by dual-energy X-ray absorptiometry
      (DXA) at the total hip and femoral neck in 2580 women and 2084 men aged 30 to 80
      years in the 2001-02 survey, and repeated in 1401 women and 1113 men in the 2007
      08 survey. Height and weight were measured and lifestyle information was
      collected through questionnaires. Data were analyzed using linear mixed models
      with second-degree fractional polynomials. From the peak at the age around 40
      years to 80 years of age, loss rates varied between 4% at the total hip and 14%
      at femoral neck in nonsmoking, physically active men with a BMI of 30 kg/m(2) to
      approximately 30% at both femoral sites in heavy smoking, physically inactive men
      with a BMI value of 18 kg/m(2) . In women also, loss rates of more than 30% were
      estimated in the lifestyle groups with a BMI value of 18 kg/m(2) . BMI had the
      strongest effect on BMD, especially in the oldest age groups, but a BMI above 30
      kg/m(2) did not exert any additional effect compared with the population average
      BMI of 27 kg/m(2) . At the age of 80 years, a lifestyle of moderate BMI to light
      overweight, smoking avoidance, and physical activity of 4 hours of vigorous
      activity per week through adult life may result in 1 to 2 standard deviations
      higher BMD levels compared with a lifestyle marked by heavy smoking, inactivity,
      and low weight. In the prevention of osteoporosis and fracture risk, the effect
      of combined lifestyles through adult life should be highlighted. (c) 2014
      American Society for Bone and Mineral Research. 

PMID- 24676862
TI  - Signal tranducers and activators of transcription: expression and function in
      anti-neutrophil cytoplasmic antibody-associated vasculitis.
AB  - Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune
      small vessel vasculitis. Despite the role of autoantibodies, T cells play an
      essential role in pathogenesis and are abnormal in AAV. Signal transducers and
      activators of transcription (STAT) affect immunoregulation and T-cell
      homeostasis. Therefore, the present study examined the ex vivo basal expression
      of the activated forms of STAT5 [phosphorylated (p)STAT5] and STAT3 (pSTAT3) in
      AAV and analyzed the function of two signaling pathways linked to these
      transcription factors. In total, 31 patients with AAV and 16 age-matched healthy
      controls (HCs) were enrolled. CD3+ T cells from peripheral blood were analyzed
      directly ex vivo by a fluorescence-activated cell sorter for basal expression of
      pSTAT5 and pSTAT3. Expression was also analyzed in T cells following short-term
      stimulation with interleukin (IL)-2 or -10. The basal expression of pSTAT5/3 in T
      cells was similar to AAV patients and HC. Following stimulation with IL-2 or -10,
      expression of pSTAT5/3 increased in AAV subjects compared with HC. Basal
      expression of pSTAT3 correlated with the relapse rate in AAV. In conclusion,
      STAT3 and STAT5 mediated signaling pathways were functionally intact in AAV
      patients and exhibited hyper-responsiveness to IL-2 and -10 stimuli. Thus, T-cell
      abnormalities in AAV are not promoted by an altered basal expression of pSTAT5/3
      or dysfunction of the IL-2/-10 signaling pathways, in which STAT5/3 are
      essential.

PMID- 24676863
TI  - Global analysis of the ground-state wrapping conformation of a charged polymer on
      an oppositely charged nano-sphere.
AB  - We investigate the wrapping conformations of a single, strongly adsorbed polymer
      chain on an oppositely charged nano-sphere by employing a reduced (dimensionless)
      representation of a primitive chain-sphere model. This enables us to determine
      the global behavior of the chain conformation in a wide range of values for the
      system parameters including the chain contour length, its linear charge density
      and persistence length as well as the nano-sphere charge and radius, and also the
      salt concentration in the bathing solution. The structural behavior of a charged
      chain-sphere complex can be described in terms of a few distinct conformational
      symmetry classes separated by continuous or discontinuous transition lines which
      are determined by means of appropriately defined (order) parameters. Our results
      can be applied to a wide class of strongly coupled polymer-sphere complexes
      including, for instance, complexes that comprise a mechanically flexible or
      semiflexible polymer chain or an extremely short or long chain and, as a special
      case, include the biologically relevant example of DNA-histone complexes. 

PMID- 24676864
TI  - Shear-induced dynamics of polymeric globules at adsorbing homogeneous and
      inhomogeneous surfaces.
AB  - The dynamics and adsorption behavior of a single collapsed homopolymer on a
      surface in shear flow is investigated by means of Brownian hydrodynamics
      simulations. We study different homogeneous and inhomogeneous surface models and
      determine dynamic state diagrams as a function of the cohesive strength, the
      adhesive strength, and the shear rate. We find distinct dynamical adsorbed states
      that are classified into rolling and slipping states, globular and coil-like
      states, as well as isotropic and prolate states. We identify two different cyclic
      processes based on trajectories of the polymer stretching and the polymer
      separation from the surface. For adsorption on an inhomogeneous surface
      consisting of discrete binding sites, we observe stick-roll motion for highly
      corrugated surface potentials. Although the resulting high surface friction leads
      to low drift velocities and reduced hydrodynamic lift forces on such
      inhomogeneous surfaces, a shear-induced adsorption is not found in the presence
      of full hydrodynamic interactions. A hydrodynamically stagnant surface model is
      introduced for which shear-induced adsorption is observed in the absence of
      hydrodynamic interactions. 

PMID- 24676865
TI  - Reduced hTERT protein levels are associated with DNA aneuploidy in the colonic
      mucosa of patients suffering from longstanding ulcerative colitis.
AB  - Longstanding ulcerative colitis (UC) is a disease of chronic inflammation of the
      colon. It is associated with the development of colorectal cancer through a
      multistep process including increasing degrees of dysplasia and DNA-ploidy
      changes. However, not all UC patients will develop these characteristics even
      during lifelong disease, and patients may therefore be divided into progressors
      who develop dysplasia or cancer, and non-progressors who do not exhibit such
      changes. In the present study, the amount of hTERT, the catalytic subunit of the
      enzyme telomerase, was estimated by using peroxidase immunohistochemistry (IHC)
      in a set of progressor and non-progressor UC colectomies. The protein levels in
      the colonic mucosa of the progressors and non-progressors were compared, and
      further comparisons between different categories of dysplastic development and to
      DNA-ploidy status within the progressors were made. Levels of hTERT were elevated
      in the colonic mucosa of the progressors and non-progressors when compared to non
      UC control samples, but no difference was observed between the hTERT levels in
      the mucosa of progressors and non-progressors. The levels of hTERT associated
      with levels of Ki67 to a significant degree within the non-progressors. hTERT
      expression in lesions with DNA-aneuploidy were decreased as compared to diploid
      lesions, when stratified for different classes of colonic morphology. Our results
      indicate an association between hTERT protein expression and aneuploidy in UC
      progressor colons, and also a possible protective mechanism in the association
      between hTERT and Ki67, against development of malignant features within the
      mucosa of a UC-colon.

PMID- 24676866
TI  - Sex chromosome polymorphism in guppies.
AB  - Sex chromosomes differ from autosomes by dissimilar gene content and, at a more
      advanced stage of their evolution, also in structure and size. This is driven by
      the divergence of the Y or W from their counterparts, X and Z, due to reduced
      recombination and the resulting degeneration as well as the accumulation of sex
      specific and sexually antagonistic genes. A paradigmatic example for Y-chromosome
      evolution is found in guppies. In these fishes, conflicting data exist for a
      morphological and molecular differentiation of sex chromosomes. Using molecular
      probes and the previously established linkage map, we performed a cytogenetic
      analysis of sex chromosomes. We show that the Y chromosome has a very large
      pseudoautosomal region, which is followed by a heterochromatin block (HCY)
      separating the subtelomeric male-specific region from the rest of the chromosome.
      Interestingly, the size of the HCY is highly variable between individuals from
      different population. The largest HCY was found in one population of Poecilia
      wingei, making the Y almost double the size of the X and the largest chromosome
      of the complement. Comparative analysis revealed that the Y chromosomes of
      different guppy species are homologous and share the same structure and
      organization. The observed size differences are explained by an expansion of the
      HCY, which is due to increased amounts of repetitive DNA. In one population, we
      observed also a polymorphism of the X chromosome. We suggest that sex chromosome
      linked color patterns and other sexually selected genes are important for
      maintaining the observed structural polymorphism of sex chromosomes. 

PMID- 24676867
TI  - SNP array detects chromosome aberrations that we thought do not exist: the first
      case of an isochromosome Xp (i(X)(p10)).

PMID- 24676868
TI  - Framework negotiations: diagnostic insights among alternative medical
      practitioners participating in integrative medicine case conferences.
AB  - Medical anthropology concerns itself with cultural interpretations of health and
      illness in complex pluralistic societies whose members incorporate multiple
      strategies to address health issues. This research explored the variety of
      complementary and alternative medicine (CAM) topics introduced into biomedically
      structured clinical evaluation. A field study of routine case conferences held
      within a clinical fellowship program in integrative medicine (IM) provided the
      ideal setting to explore contrasting conceptualizations of disease. Study results
      yielded five core sources of information sought by CAM practitioners, typically
      not addressed in biomedicine: social relations history within family of origin,
      emotional health, energetic health, spiritual health, and in-depth nutritional
      evaluation. 

PMID- 24676869
TI  - General self-efficacy and its relationship to self-reported mental illness and
      barriers to care: a general population study.
AB  - Given the prevalence of mental illness worldwide, it is important to better
      understand the dynamics of mental health help-seeking behavior to improve access
      to care. The aim of this study was to investigate if general self-efficacy (GSE)
      was associated with self-reported mental illness and help-seeking behavior and
      barriers to care in a randomized population. This study utilized a mailed
      questionnaire completed by 3,981 persons aged 19-64 years who resided in Western
      Sweden. GSE was measured and logistic regression models calculated, controlling
      for various sociodemographic variables. Results showed that 25% of men and 43% of
      women reported a lifetime prevalence of mental illness that they felt could have
      benefitted from treatment. Of those, 37% of the men and 27% of the women reported
      barriers to care. Men and women with low GSE were more likely to suffer from
      mental illness compared with persons high in GSE, but GSE did not enhance help
      seeking behavior or perceived barriers to care. The most prevalent barriers to
      care for both sexes were beliefs that the illness will pass by itself, doubt
      whether treatment works, lack of knowledge of where to go and feelings of shame.
      Overall, GSE scores did not differ among those who experienced various barriers
      to care with the exception of two barriers only among women.

PMID- 24676870
TI  - [Reading and writing disorder (RWD) - criteria for a speech therapist
      intervention].
AB  - BACKGROUND: Children with specific language impairments carry a high risk for the
      development of reading and writing disorders. While deficits in phonological
      encoding have been well studied, there has been little research in the german
      speaking world into the possible correlation between linguistic ability and
      reading or writing skills in elementary school children. MATERIAL AND METHODS:
      Using a group of 27 children between the ages of 8 and 11, a battery of tests
      were performed to research possible correlations between linguistic ability and
      reading and writing ability in elementary school children. RESULTS: There was a
      slight correlation between writing ability of pseudo words for vocabulary
      (r=0.48, p<0.05), sentence repeating (r=0.50, p<0.05) and grammar (r=0.58,
      p<0.01). Vocabulary and grammar however were significantly correlated with
      writing ability (r=0.38, p<0.05). In particular, phonological encoding was
      significantly worse compared to receptive or expressive abilities. 67% of the
      children with RWD had also linguistic deficits, 15% had only phonological
      deficits and the remaining 18% no language deficits. CONCLUSION: The results
      confirm both delays as comorbid problems. Therefore it is clear that when a
      reading and writing disorder is present, then speech and language problems should
      be also suspected and appropriate speech therapy instituted.

PMID- 24676871
TI  - [High-frequency jet ventilation in otorhinolaryngology - surgical and
      anaesthesiologic issues].
AB  - BACKGROUND: High-frequency jet ventilation (HFJV) through thin catheters creates
      more room for surgical procedures in laryngotracheal surgery, while few
      contraindications exist. In contrast, the anaesthesiologist has to cope with
      reduced monitoring and numerous contraindications. Therefore, every participating
      discipline has to thoroughly know the method. We report our experiences with HFJV
      and focus on relevant points, which contribute to a safe and cooperative
      procedure. MATERIAL AND METHODS: We performed a retrospective chart review for
      patients, who were operated for benign laryngotracheal lesions using HFJV at the
      Hannover Medical School, Department of Otorhino-Laryngology between June 2012 and
      February 2013. We analyze patient characteristics, complications and important
      anaesthesiologic and operative steps. RESULTS: A total of 46 cases of
      microlaryngoscopies and tracheoscopies were included in this study. The median
      body mass index was 27 kg/m(2). According to the ASA-classification, 24% of
      patients were categorized class I, 54% class II and 22% class III. In 2 cases we
      had reversible, peripheral desaturations down to 70%. In one case, emergent re
      intubation with an endotracheal tube was inevitable due to rapid desaturation
      below 50%. Further complications were not observed. CONCLUSION: HFJV represents a
      safe ventilation approach in laryngotracheal surgery, when patients are
      thoroughly selected. Especially the surgeon benefits from more room in the
      operating field. Obesity, reflux and cardiopulmonary diseases have to be
      evaluated well, as these can represent relative contraindications. Individual
      decisions can be made under consideration of all comorbidities.

PMID- 24676872
TI  - [Vocal cord paralysis--analysis of a cohort of 400 patients].
AB  - Vocal cord paralysis has diverse etiologies. In the present study, vocal chord
      paralysis caused by surgery/trauma was present in more than two thirds of the
      cases, followed by primary malignancy-associated paralysis. Thyroidectomy was the
      most common cause in bilateral paresis, especially if performed in recurrent or
      malignant disease. Voice therapy was promising in pa-tients with unilateral
      paresis and hoarseness as main symptom. Persistent dysphonia due to insufficiency
      of the glottic closure led to an operative glottis restricting procedure in only
      6% of cases. In almost half the patients with dyspnea as the main symp-tom of
      bilateral vocal cord paresis, temporary tracheotomy or surgical glottis widening
      procedures had to be performed. The group of idiopathic and traumatic paresis
      patients showed the best spontaneous recovery within the first 12 months in
      comparison to primary malignancy-associated paralysis, which showed no recovery
      of the recurrens nerve.

PMID- 24676874
TI  - Improving child self-regulation and parenting in families of pre-kindergarten
      children with developmental disabilities and behavioral difficulties.
AB  - The transition to school may be particularly difficult for children with
      developmental disabilities and behavioral difficulties. Such children are likely
      to experience problems with self-regulation skills, which are critical to school
      adjustment. Additionally, inconsistent discipline practices and low parental
      involvement in children's schooling may contribute to a poor transition to
      school. This study employed a randomized clinical trial to examine the effects of
      a school readiness intervention that focused on children's self-regulation skills
      as well as parenting and parental involvement in school. Results showed that the
      intervention had positive effects on children's self-regulation in kindergarten
      as measured by teacher and observer reports. Additionally, the intervention
      significantly reduced ineffective parenting prior to school entry, which in turn
      affected parental involvement. This finding is significant because it
      demonstrates that parental involvement in school may be increased by efforts to
      improve parenting skills in general. Overall, the study demonstrated that school
      adjustment across kindergarten among children with developmental disabilities and
      behavioral difficulties can be enhanced through an intervention aimed
      specifically at improving school readiness skills. 

PMID- 24676873
TI  - The effect of sunitinib on the plasma exposure of intravenous paracetamol and its
      major metabolite: paracetamol glucuronide.
AB  - The study aimed to examine the effect of sunitinib on the plasma exposure of
      intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both
      drugs share metabolic pathways in the liver, and the drug interactions between
      sunitinib and paracetamol administered in higher doses were reported. These
      interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were
      divided into three groups (6 animals each): rabbits receiving sunitinib and
      paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group
      receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and
      paracetamol was administrated intravenously (35 mg/kg). Blood samples for
      sunitinib and SU12662 assays were collected up to 96 h after drug administration
      and for paracetamol and paracetamol glucuronide up to 300 min after drug
      administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      and bilirubin were analysed before and after drug administration. A number of
      pharmacokinetic parameters were analysed. There were no differences in the levels
      of AST, ALT, and bilirubin among the groups at either time point. Significantly
      higher values of AUC0-t , AUC0-infinity , and C max and lower clearance and
      volume of distribution of paracetamol were observed in group PC vs. group SUN +
      PC (p < 0.01). The maximum plasma concentration of paracetamol glucuronide tended
      to be higher in group PC 213.27 MUg/mL (90 % CI 1.06, 1.25; p = 0.0267).
      Statistically significant differences were revealed for paracetamol glucuronide
      mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p =
      0.0375). The mean t max of paracetamol glucuronide was similar in both groups:
      SUN + PC and group PC (15 and 20 min, respectively). The mean t max of sunitinib
      was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p =
      0.0134). At the studied doses, neither of the drugs, whether administered alone
      or together, had hepatotoxic effects. The present study was not able to confirm
      that sunitinib, administered at low doses in conjunction with paracetamol,
      displays a hepatoprotective effect. Significant differences were observed in some
      pharmacokinetic parameters of paracetamol. 

PMID- 24676875
TI  - Half-dose gadobenate dimeglumine versus standard-dose gadodiamide in dynamic
      magnetic resonance imaging of non-cirrhotic livers: a retrospective intra
      individual crossover comparison.
AB  - PURPOSE: The purpose of this study was to compare enhancement characteristics of
      half-dose gadobenate dimeglumine (0.05 mmol kg(-1)) with standard-dose
      gadodiamide (0.10 mmol kg(-1)), in the assessment of hepatic vessels and lesions,
      using retrospective intra-individual crossover comparison methodology. METHODS:
      Ethics committee approval was obtained. From 2004 to 2012, 21 patients underwent
      MRI examination with both standard-dose gadodiamide and half-dose gadobenate
      dimeglumine, using the same liver MRI protocol at 1.5 T. Eighteen patients whose
      scans showed no artifacts were selected. Quality of liver lesion [12 hemangiomas,
      7 focal nodular hyperplasias (FNHs)] and liver vessel enhancement, and the global
      diagnostic quality of studies were ranked on a scale of 1-4 by two independent
      radiologists. Contrast-to-noise ratio (CNR) and % enhancement of liver vessels
      and lesions were calculated based on region of interest, signal intensity, and
      noise standard deviation measurements performed at 0, 20 s, 1, 3, and 5 min post
      contrast injection. Qualitative and quantitative results were compared using the
      paired Wilcoxon signed rank and Student's t-tests, respectively. RESULTS: No
      qualitative differences were noted in enhancement of liver vessels, hemangiomas,
      and FNHs. There was no statistically significant difference between the global
      diagnostic qualities of scans performed with the two contrast agents.
      Quantitatively, liver vessels and hemangiomas did not demonstrate statistically
      significant differences in contrast enhancement. At 20 s, FNHs achieved higher
      CNR (P = 0.02) with gadodiamide. CONCLUSION: Half-dose gadobenate dimeglumine
      results in similar contrast enhancement compared to standard-dose gadodiamide in
      assessment of liver vessels, hemangiomas, and FNHs, and is a reasonable
      alternative to standard doses of extracellular agents in dynamic liver MRI.

PMID- 24676876
TI  - Salvage surgery for local residual or recurrent pharyngeal cancer after
      radiotherapy or chemoradiotherapy.
AB  - OBJECTIVES/HYPOTHESIS: Local residual or recurrent pharyngeal cancer after
      definitive radiotherapy (RT) or chemoradiotherapy (CRT) is correlated to poor
      prognosis. We analyzed the efficacy of salvage surgery for patients with local
      residual or recurrent pharyngeal cancer after RT or CRT. STUDY DESIGN:
      Retrospective clinical study with chart review. METHODS: Between 2001 and 2011,
      we treated 207 patients with resectable pharyngeal cancer, including 98 patients
      with oropharyngeal cancer (OPC) and 109 patients with hypopharyngeal cancer (HPC)
      who received definitive RT or CRT. Local residual or recurrence developed in 59
      patients (23 with OPC; 36 with HPC), of whom 42 (18 with OPC; 24 with HPC)
      underwent salvage surgery. These 42 patients were investigated in this study.
      RESULTS: The initial treatments were RT; RT with induction chemotherapy (IC); and
      concurrent CRT in 12, 9, and 21 patients, respectively. The median radiation dose
      was 70 Gy. The 3-year disease-specific survival rate after salvage surgery was
      40% (median, 26 months). The significant prognostic factors were stage IV prior
      to initial therapy (P = .049), development of concurrent local and regional
      relapse (P = .02), and OPC (P = .04). CONCLUSIONS: The efficacy of salvage
      surgery for local residual or recurrent pharyngeal cancer was limited. Oropharynx
      origin, stage IV prior to initial therapy, and concurrent regional relapses were
      significantly poor prognostic factors. Salvage surgery for HPC is worth
      challenging aggressively. Conversely, the indication of salvage surgery for OPCs
      should be carefully considered because of its low cure rate.

PMID- 24676877
TI  - A randomized, open-label clinical trial of tasisulam sodium versus paclitaxel as
      second-line treatment in patients with metastatic melanoma.
AB  - BACKGROUND: Tasisulam sodium (hereafter referred to as tasisulam) is a novel,
      highly albumin-bound agent that demonstrated activity in a phase 2 melanoma
      study. METHODS: In this open-label phase 3 study, patients with AJCC stage IV
      melanoma received tasisulam (targeting an albumin-corrected exposure of 1200-6400
      h (hour).MUg/mL on day 1) or paclitaxel (80 mg/m(2) on days 1, 8, and 15) every
      28 days as second-line treatment. RESULTS: The study was placed on clinical hold
      after randomization of 336 patients when a safety review indicated an imbalance
      of possibly drug-related deaths in the tasisulam arm. Efficacy results for
      tasisulam versus paclitaxel revealed a response rate of 3.0% versus 4.8%, a
      median progression-free survival of 1.94 months versus 2.14 months (P = .048),
      and a median overall survival of 6.77 months versus 9.36 months (P = .121). The
      most common drug-related grade >=3 laboratory toxicities (graded according to
      Common Terminology for Adverse Events [version 3.0]) were thrombocytopenia
      (18.9%) for patients treated with tasisulam and neutropenia/leukopenia (8.7%)
      among those receiving paclitaxel. There were 13 possibly related deaths reported
      to occur on the study, with the majority occurring during cycle 2 in the setting
      of grade 4 myelosuppression, all in the tasisulam arm. Investigation of the
      unexpectedly high rate of hematologic toxicity revealed a subset of patients with
      low tasisulam clearance, leading to drug accumulation and high albumin-corrected
      exposure in cycle 2. CONCLUSIONS: Although the study was stopped early because of
      safety issues in the tasisulam arm, tasisulam was considered unlikely to be
      superior to paclitaxel, and paclitaxel activity in the second-line treatment of
      melanoma was much lower than expected. The toxicity imbalance was attributed to
      an unexpectedly low tasisulam clearance in a subset of patients, underscoring the
      importance of pharmacokinetic monitoring of compounds with complex dosing, even
      in late-phase studies.

PMID- 24676878
TI  - Berberine hydrochloride prevents postsurgery intestinal adhesion and inflammation
      in rats.
AB  - Intestinal adhesion, characterized by connection of the loops of the intestine
      with other abdominal organs by fibrous tissue bands, remains an inevitable event
      of abdominal operations and can cause a number of complications. Berberine
      hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal
      medicine, is characterized by diverse pharmacological effects, such as anticancer
      and lower elevated blood glucose. This study is designed to investigate the
      effects of berberine on adhesion and inflammation after abdominal surgeries and
      the underlying molecular mechanisms. Adhesion severity grades and collagen
      deposition were assessed 14 days after surgery. We evaluated the levels of
      intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin
      1beta (IL-1beta), IL-6, transforming growth factor beta (TGF-beta), tumor
      necrosis factor-alpha (TNF-alpha), and examined transforming growth factor
      activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor
      kappaB (NF-kappaB) signaling. The surgery group experienced the most severe
      adhesions, and berberine strikingly reduced the density and severity of adhesion.
      Results showed significant lower expression of IL-1beta, IL-6, TGF-beta, TNF
      alpha, and ICAM-1, in berberine groups compared with the operation group.
      Activities of phosphorylated JNK and phosphorylated NF-kappaB were inhibited in
      the berberine groups compared with the surgery group. Our novel findings
      identified berberine hydrochloride as a promising strategy to prevent adhesion by
      downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and
      TAK1/NF-kappaB signaling after abdominal surgery, which brought out a good
      therapeutic approach for the development of clinical application for
      postoperative abdominal adhesion and inflammation. 

PMID- 24676879
TI  - Justification of anthropometric empirical indicator (AEI) by digital chest and
      pelvic X-rays: a comparative scenario with DXA on obesity grounds.
AB  - BACKGROUND: Obesity is an abnormal accumulation of body fat directly proportional
      to reduced life expectancy. Treatment of this ailment should be preceded by
      proper and accurate assessment of the degree of obesity. OBJECTIVES: The main
      objective is the justification of anthropometric empirical indicator (AEI) by the
      utilization of chest and pelvic radiographs, so that precise measurement of
      obesity on economical grounds can be manifested. Also, the subsequent objective
      is to establish a comparative scenario between dual energy X-ray absorptiometry
      (DXA) and novel, portable, bioelectric impedance analysis (BIA)-based body
      composition analyzer, MI-105 (Meditech International Inc. India). MATERIALS AND
      METHODS: The cross-sectional design was adopted in the present study, in which 20
      female participants from urban south India were involved. The measurements of
      body composition, anthropometry and chest (covering the region from neck to
      abdomen) as well as hip radiography of the studied population were acquired.
      RESULTS: The higher significant difference of <=0.001 was evidenced in all female
      studied population in the main body composition parameters measured by DXA and
      low-cost BIA. The same framework of significance is applicable to AEI, AEI (image
      morphed) and AEI (image automatic). CONCLUSION: The novel-derived parameters: AEI
      (image morphed) and AEI (image automatic) can precisely gauge obesity and can be
      the effective alternatives for high-cost DXA. In addition, low-cost BIA-based
      body composition analyzer can also be the better substitute for DXA.

PMID- 24676880
TI  - Amino acids in human and animal nutrition.
AB  - Amino acids are key components of human and animal nutrition, both as part of a
      protein-containing diet, and as supplemented individual products. In the last 10
      years there has been a marked move away from the extraction of amino acids from
      natural products, which has been replaced by efficient fermentation processes
      using nonanimal carbon sources. Today several amino acids are produced in
      fermentation plants with capacities of more than 100,000 tonnes to serve the
      requirements of animal feed and human nutrition. The main fermentative amino
      acids for animal nutrition are L-lysine, L-threonine, and L-tryptophan. DL
      Methionine continues to be manufactured for animal feed use principally by
      chemical synthesis, and a pharmaceutical grade is manufactured by enzymatic
      resolution. Amino acids play an important role in medical nutrition, particularly
      in parenteral nutrition, where there are high purity requirements for infusion
      grade products. Amino acids are also appearing more often in dietary supplements,
      initially for performance athletes, but increasingly for the general population.
      As the understanding of the effects of the individual amino acids on the human
      metabolism is deepened, more specialized product mixtures are being offered to
      improve athletic performance and for body-building.

PMID- 24676881
TI  - Histomorphochemical comparison of microfracture as a first-line and a salvage
      procedure: is microfracture still a viable option for knee cartilage repair in a
      salvage situation?
AB  - Microfracture is considered as the first-line procedure for knee cartilage
      repair, but the results of microfracture seem less predictable and rather
      controversial in a salvage situation. Thus, the purpose of the study was to
      histomorphochemically compare microfracture as a salvage procedure with
      microfracture as a first-line procedure in a rabbit model. We hypothesized that
      microfracture in a salvage situation would result in histomorphochemically
      inferior cartilage repair compared to microfracture as a first-line procedure,
      and the inferiority would be attributed to less migration of reparable marrow
      cells to the defect due to destruction of microarchitecture of the subchondral
      bone. Thirty-six New Zealand white rabbits were divided into three groups: (i)
      untreated full-thickness chondral defect, (ii) single microfracture treatment
      (first microfracture group), and (iii) repeated microfracture in 8 weeks after
      the first procedure (second microfracture group). In each group, rabbits were
      sacrificed at the end of 8 weeks, and osteochondral specimens at the repair sites
      were obtained for histomorphochemical analysis. Results showed that microfracture
      as a salvage procedure resulted in overall inferior cartilage repair
      histomorphochemically compared with microfracture as a first-line procedure,
      which correlated with deteriorative changes in the quality of underlying
      subchondral bone rather than intrinsic incapability to recruit the reparative
      cells in the defect area. In conclusion, although a comparable number of
      reparable cells and a mechanically weakened subchondral bone are anticipated,
      more study is necessary to clearly determine when a microfracture should be
      performed in a situation.

PMID- 24676882
TI  - Isoquercitrin inhibits the progression of liver cancer in vivo and in vitro via
      the MAPK signalling pathway.
AB  - Liver cancer is a malignant tumour with high morbidity and fatality rates that is
      common worldwide. At present, the clinical approaches to treating primary liver
      cancer include partial hepatectomy, systemic or local chemotherapy, radiotherapy,
      radiofrequency ablative surgery and liver transplantation. However, all of these
      approaches have shortcomings, including poor prognosis and numerous side-effects.
      A large number of studies have proven that many effective ingredients in
      traditional Chinese medicine, particularly the flavonoid compounds extracted from
      plants, have achieved breakthroughs in terms of enhancing the effects and
      reducing the toxicity of chemotherapy and radiotherapy, preventing tumour
      metastasis and relapse after surgery, alleviating the clinical symptoms of
      advanced tumours, improving the quality of life of the patient with tumours and
      extending patient long-term survival. The purpose of the present study was to
      investigate the impact of isoquercitrin, the flavonoid from Bidens bipinnata L.
      extract, on the progression of liver cancer and to achieve a deeper understanding
      of the biological characteristics of isoquercitrin's involvement in the
      progression of liver cancer. In the in vitro experiments, isoquercitrin was found
      to strongly inhibit the proliferation of human liver cancer cells, promote the
      apoptosis of human liver cancer cells, and block the cell cycle in the G1 phase.
      Isoquercitrin activated caspase-3, -8 and -9, inhibited the expression level of
      ERK and p38MAPK protein phosphorylation, and promoted the phosphorylation of JNK.
      Additionally, isoquercitrin reduced the expression level of PKC in human liver
      cancer cells. In the in vivo experiments, isoquercitrin was also found to
      significantly inhibit the growth of transplanted tumours in nude mice. The
      present study confirmed that isoquercitrin could inhibit the progression of human
      liver cancer in vivo and in vitro, and the molecular mechanism of isoquercitrin
      may be closely associated with the MAPK and PKC signalling pathways.

PMID- 24676883
TI  - Analysis of proteomic changes in colored mutants of Xanthophyllomyces dendrorhous
      (Phaffia rhodozyma).
AB  - The yeast Xanthophyllomyces dendrorhous synthesizes astaxanthin as its most
      prevalent xanthophyll derivative. Comparisons between the protein profiles of
      mutant lines of this yeast can provide insight into the carotenogenic pathway.
      Differently colored mutants (red, orange, pink, yellow, and white) were obtained
      from this yeast species, and their protein profiles were determined using two
      dimensional polyacrylamide gel electrophoresis (2DE). Individual proteins
      differentially expressed were identified using mass spectrometry. The red mutants
      hyperproduced total carotenoids (mainly astaxanthin), while in white and orange
      mutants, mutagenesis affected the phytoene dehydrogenase activity as indicated by
      the accumulation of phytoene. Inactivation of astaxanthin synthase after the
      mutagenic treatment was evident in beta-carotene accumulating mutants.
      Differences in the proteomic profiles of wild-type X. dendrorhous and its colored
      mutants were demonstrated using 2DE. Of the total number of spots detected in
      each gel (297-417), 128 proteins were present in all strains. The red mutant
      showed the greatest number of matches with respect to the wild type (305 spots),
      while the white and yellow mutants, which had reduced concentrations of total
      carotenoids, presented the highest correlation coefficient (0.6) between each
      other. A number of differentially expressed proteins were sequenced, indicating
      that tricarboxylic acid cycle and stress response proteins are closely related to
      the carotenogenic process.

PMID- 24676884
TI  - Numerical modeling of capillary electrophoresis - electrospray mass spectrometry
      interface design.
AB  - Capillary electrophoresis hyphenated with electrospray mass spectrometry (CE-ESI
      MS) has emerged in the past decade as one of the most powerful bioanalytical
      techniques. As the sensitivity and efficiency of new CE-ESI-MS interface designs
      are continuously improving, numerical modeling can play important role during
      their development. In this review, different aspects of computer modeling and
      simulation of CE-ESI-MS interfaces are comprehensively discussed. Relevant
      essentials of hydrodynamics as well as state-of-the-art modeling techniques are
      critically evaluated. Sheath liquid-, sheathless-, and liquid-junction interfaces
      are reviewed from the viewpoint of multidisciplinary numerical modeling along
      with details of single and multiphase models together with electric field
      mediated flows, electrohydrodynamics, and free fluid-surface methods. Practical
      examples are given to help non-specialists to understand the basic principles and
      applications. Finally, alternative approaches like air amplifiers are also
      included. (c) 2014 Wiley Periodicals, Inc. Mass Spec Rev 34: 558-569, 2015. 

PMID- 24676885
TI  - Reductions in heel bone quality across gestation are attenuated in pregnant
      adolescents with higher prepregnancy weight and greater increases in PTH across
      gestation.
AB  - Few studies have examined the effect of maternal calcium intake and vitamin D
      status on bone health across gestation in pregnant adolescents. This study aimed
      to characterize maternal bone quality and determinants of bone-quality change
      across gestation in pregnant adolescents. Healthy pregnant adolescents (n = 156;
      aged 13 to 18 years) with singleton pregnancies and at 12 to 30 weeks gestation
      at enrollment were recruited from two urban maternity clinics in Baltimore, MD,
      and Rochester, NY, for this prospective longitudinal study. Maternal serum was
      collected at midgestation and at delivery for assessment of bone biomarkers and
      calcitropic hormones. Maternal bone quality (assessed by heel ultrasound) and
      sonographic fetal biometry were measured up to three times across pregnancy.
      Racially diverse teens (64.7% African American, 35.3% white) were followed from
      21.0 (interquartile range [IQR] 17.3, 27.0) weeks of gestation until delivery at
      40.0 (IQR 39.0, 40.7) weeks. Significant decreases in calcaneal speed of sound
      (SOS), broadband ultrasound attenuation (BUA), and quantitative ultrasound index
      (QUI) (-9.2 +/- 16.1 m/s, -3.2 (-8.0, 2.1) dB/MHz and -5.3 +/- 8.8, respectively)
      were evident across pregnancy. Multivariate analysis controlling for baseline
      measures and measurement intervals was used to identify independent predictors of
      normalized (per week) calcaneal bone loss. Weekly decreases in bone quality were
      not significantly associated with maternal calcium intake or 25(OH)D
      concentration. Greater weekly reductions in calcaneal bone quality were evident
      in teens with lower prepregnancy weight (BUA, p = 0.006 and QUI, p = 0.012) and
      among those with lower weekly increase in PTH (SOS, p = 0.046). Overall,
      significant decreases in calcaneal bone quality occurred across pregnancy in
      adolescents, but the magnitude of this loss was attenuated in those with greater
      prepregnancy weight and weekly increases in PTH. Further studies are needed to
      understand the role of elevated PTH and greater prepregnancy weight in preserving
      adolescent bone during pregnancy.

PMID- 24676886
TI  - Development and validation of the Prenatal Diagnostic Procedures Anxiety Scale.
AB  - OBJECTIVES: As there are currently no specific measures of anxiety due to
      prenatal diagnostic procedures, the aim of the study was to develop and validate
      a new measure called the Prenatal Diagnostic Procedure Anxiety Scale (PDPAS).
      METHODS: Seventy-four pregnant women scheduled for amniocentesis and ultrasound
      completed the PDPAS, the State-Trait Anxiety Inventory, the Edinburgh Postnatal
      Depression Scale, and the Perceived Stress Scale before undergoing the diagnostic
      procedure. Reliability, concurrent validity, factor structure, scale sensitivity,
      and specificity were analyzed. Differences between amniocentesis and ultrasound
      groups in the PDPAS score were analyzed with a t-test. RESULTS: The final scale
      comprised 11 items and two subscales measuring 'fear of procedure' and 'fear of
      abnormal result'. Concurrent validity analysis showed that the PDPAS is an
      independent measure of anxiety. At a cut-off score of >11, sensitivity was 75.0%
      and specificity was 72.01% with moderate accuracy. Fear of procedure was higher
      in the amniocentesis group, whereas fear of abnormal result was equally present
      in both amniocentesis and ultrasound groups. CONCLUSION: The PDPAS has good
      internal consistency and concurrent validity with satisfactory psychometric
      characteristics. As a short measure of situation-specific anxiety, it can be used
      as a screening tool in prenatal clinical settings.

PMID- 24676887
TI  - Low-energy femoral shaft fractures after long-term alendronate therapy: report of
      seven cases.
AB  - BACKGROUND: There is increasing evidence suggesting a high incidence of low
      energy fractures of the diaphysis or the proximal femur in patients receiving
      bisphosphonates for a long time. Bisphosphonate-related femoral fractures occur
      after low-energy trauma and have a typical simple transverse or oblique
      radiographic pattern, with focal or generalized increased cortical thickness,
      cortical beaking, and medial spiking. MATERIALS AND METHODS: This article
      presents six female patients who experienced seven transverse femoral diaphysis
      and subtrochanteric fractures with cortical thickening and beaking; all patients
      had alendronate treatment for 4-10 years (average, 9 years) before their
      fracture. RESULTS: The typical radiographic findings, long-term administration of
      alendronate, low-energy mechanism of fracture, and related literature support the
      fact that the fractures in the patients presented in this series should be
      related to alendronate treatment. CONCLUSION: Until definite evidence is
      available, alendronate treatment in patients with osteoporosis is not now
      prohibited by the healthcare authorities, probably because its beneficial
      influence outweighs the adverse effects. However, this adverse effect deserves
      attention of medical practitioners; physicians should be alert on alendronate's
      possible suppressive effect on bone turnover, which in turn may be responsible
      for the occurrence of femoral fractures.

PMID- 24676888
TI  - Arthroscopic synovectomy in the treatment of functional ankle instability:
      outcomes and gait analysis.
AB  - BACKGROUND: Natural consequence of repetitive ankle sprains is the chronic ankle
      instability. Objective of this study was to clarify the gait patterns of
      functional ankle instability (FAI) patients after arthroscopic synovectomy, but
      also assessment of postoperative recovery. PATIENTS AND METHODS: Arthroscopic
      synovectomy was performed to 14 FAI patients with history of unilateral
      repetitive ankle sprains, pain, and subjective sensation of instability. At a
      mean 54 months of follow-up (27-84), clinical assessment was conducted with
      respect to pain, number of ankle sprains, and American Orthopaedics Foot and
      Ankle Society (AOFAS) scores. Gait analysis was conducted to determine the
      temporospatial, kinetic and kinematic parameters at the last follow-up. RESULTS:
      Mean AOFAS scores increased from 68 (range 55-75) to 89 (range 77-100) points (P
      < 0.01). Mean ankle sprains was 13 in a period of 23 (range 14-48) months (0.58
      per month) and decreased to three sprains in a mean time period of 54 months
      (0.053 per month) (P < 0.01). Mean preoperative and postoperative VAS scores were
      8.0 and 2.9, respectively (P < 0.01). During gait analysis, no significant
      differences were found in ankle joint, including foot progression angles, ankle
      dorsi-plantar flexion degrees and ground reaction forces (P > 0.01). Among
      temporospatial parameters, only double support time showed a significant
      difference (P < 0.01). All patients were satisfied from the procedure and
      returned to their previous activity level. CONCLUSION: Improved long-term
      clinical results and scores were obtained in our patient group when compared with
      the preoperative scores. Also, three-dimensional gait analysis showed that the
      involved ankles demonstrate similar gait patterns to the uninvolved ankles in
      patients with FAI.

PMID- 24676889
TI  - Court decisions on medical malpractice.
AB  - BACKGROUND: Recent studies on court cases dealing with medical malpractice are
      few and far between. This retrospective study, therefore, undertakes an analysis
      of medical malpractice lawsuits brought before regional courts in two judicial
      districts of the federal state of Hesse. METHODS: Over a 5-year period (2006
      2010), 232 court decisions on medical malpractice taken by the regional courts
      (Landgericht) of Kassel and Marburg were evaluated according to medical
      discipline, diagnosis, therapy, relevant level of care, charge of neglect of duty
      by the claimant party, outcome of the lawsuit, and further criteria. RESULTS:
      With certain overlaps, the disciplines most frequently confronted with claims of
      medical malpractice were accident surgery and orthopedics (30.2%; n = 70),
      dentistry (16.4%; n = 38), surgery (12.1%; n = 28), and gynecology and obstetrics
      (7.8%; n = 18), followed by the remaining medical disciplines (38.8%; n = 90).
      Malpractice allegations were brought against the practice-based sector in 35.8 %
      (n = 83) of cases, the hospital-based sector in 63.3% (n = 147) of cases, and
      other sectors in 0.9% (n = 2) of cases. The allegation grounds included false
      administration of treatment (67.2%; n = 156), false indication of treatment
      (37.1%; n = 86), false diagnosis (31.5%; n = 73), and/or organizational
      negligence (13.8%; n = 32). A breach of duty to inform was given as grounds for
      the claim in 38.8% (n = 90) of cases. A significant majority of 65.6% (n = 152)
      of cases ended in a court settlement. Of the cases, 18.9% (n = 44) were concluded
      by claim withdrawal, 11.2% (n = 26) by claim dismissal and 2.6% (n = 6) by
      criminal sentence. Of the cases, 1.7% (n = 4) were for purposes of securing
      evidence. CONCLUSION: Although there was no conclusive evidence of malpractice,
      two thirds of the cases ended in a court settlement. On the one hand, this
      outcome reduces the burden on the courts, but on the other, it can in the long
      term give rise to expectations that doctors will accept liability even in cases
      of inevitable deterioration following due and proper treatment.

PMID- 24676890
TI  - Jejunal pouch recurrence after extended surgery for gastric cancer: report of a
      case.

PMID- 24676891
TI  - Intravenous and intraperitoneal paclitaxel with S-1 for refractory pancreatic
      cancer with malignant ascites: an interim analysis.
AB  - OBJECTIVES: Here, we reported an interim analysis of feasibility and safety in
      the first 10 cases of 30 cases in a phase II trial of intravenous and
      intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory
      pancreatic cancer with malignant ascites. METHODS: Paclitaxel was administered
      intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8 every
      3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days,
      followed by 7-day rest. RESULTS: Between April 2011 and February 2012, ten
      patients were enrolled. A partial response was achieved in two patients (20%) and
      a disease control rate of 50%. The median time to progression and overall
      survival were 2.1 and 3.4 months, respectively. Malignant ascites was completely
      resolved in two patients (20%). Major grade 3/4 adverse events were
      myelosuppression including neutropenia (50%) and catheter-related infection
      (10%). CONCLUSIONS: This novel combination chemotherapy was feasible and showed
      promising results in pancreatic cancer patients with malignant ascites (clinical
      trial registration number: UMIN000005306).

PMID- 24676892
TI  - Octreotide long-acting repeatable use among elderly patients with carcinoid
      syndrome and survival outcomes: a population-based analysis.
AB  - BACKGROUND: Octreotide long-acting repeatable (LAR) is indicated for the
      treatment of carcinoid syndrome and diarrhea related to VIPoma, and may delay
      tumor growth in patients with neuroendocrine tumors (NETs). To the authors'
      knowledge, the pattern of octreotide LAR use in clinical practice and its impact
      on survival outcomes has not been well documented. METHODS: Using the
      Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors
      identified patients with NET aged >= 65 years who were diagnosed between July
      1999 and December 2007. Patients with US Food and Drug Administration-approved
      indications for octreotide LAR were identified from Medicare claims. Multivariate
      logistic regression was performed to ascertain factors associated with octreotide
      LAR use, whereas the Cox proportional hazards model was used to evaluate the
      impact of octreotide LAR on survival. RESULTS: Among those with Food and Drug
      Administration-approved indications, 245 of 4848 patients with distant-stage
      disease (51%) and 81 of 807 patients with local/regional disease (10%) initiated
      treatment with octreotide LAR within 6 months of diagnosis. Multivariate logistic
      regression indicated that among those with distant-stage disease, older age (>=
      80 years vs 65-69 years) (odds ratio [OR], 0.43; 95% confidence interval [95%
      CI], 0.23-0.81), female sex (OR, 0.62; 95% CI, 0.40-0.97), and living in the
      South (vs Northeast) (OR, 0.36; 95% CI, 0.18-0.72) were associated with a lower
      likelihood of using octreotide LAR. The multivariate proportional hazards model
      showed that octreotide LAR provided a significant 5-year survival benefit for
      patients with distant-stage disease (hazards ratio, 0.61; P <= .001), whereas
      this survival benefit was not shown for the patients with local/regional stage
      (hazards ratio, 0.88; P = .563). CONCLUSIONS: The results of this retrospective
      study suggest a possible survival benefit for the use of octreotide LAR in
      elderly patients with distant-stage NET with carcinoid syndrome. The results of
      the current study also suggest that octreotide LAR is underused in this
      population despite recommended guidelines.

PMID- 24676893
TI  - Hexicon 2: automated processing of hydrogen-deuterium exchange mass spectrometry
      data with improved deuteration distribution estimation.
AB  - Hydrogen-deuterium exchange (HDX) experiments analyzed by mass spectrometry (MS)
      provide information about the dynamics and the solvent accessibility of protein
      backbone amide hydrogen atoms. Continuous improvement of MS instrumentation has
      contributed to the increasing popularity of this method; however, comprehensive
      automated data analysis is only beginning to mature. We present Hexicon 2, an
      automated pipeline for data analysis and visualization based on the previously
      published program Hexicon (Lou et al. 2010). Hexicon 2 employs the sensitive
      NITPICK peak detection algorithm of its predecessor in a divide-and-conquer
      strategy and adds new features, such as chromatogram alignment and improved
      peptide sequence assignment. The unique feature of deuteration distribution
      estimation was retained in Hexicon 2 and improved using an iterative
      deconvolution algorithm that is robust even to noisy data. In addition, Hexicon 2
      provides a data browser that facilitates quality control and provides convenient
      access to common data visualization tasks. Analysis of a benchmark dataset
      demonstrates superior performance of Hexicon 2 compared with its predecessor in
      terms of deuteration centroid recovery and deuteration distribution estimation.
      Hexicon 2 greatly reduces data analysis time compared with manual analysis,
      whereas the increased number of peptides provides redundant coverage of the
      entire protein sequence. Hexicon 2 is a standalone application available free of
      charge under http://hx2.mpimf-heidelberg.mpg.de.

PMID- 24676894
TI  - Improving the sensitivity of mass spectrometry by using a new sheath flow
      electrospray emitter array at subambient pressures.
AB  - Arrays of chemically etched emitters with individualized sheath gas capillaries
      were developed to enhance electrospray ionization (ESI) efficiency at subambient
      pressures. By incorporating the new emitter array in a subambient pressure
      ionization with nanoelectrospray (SPIN) source, both ionization efficiency and
      ion transmission efficiency were significantly increased, providing enhanced
      sensitivity in mass spectrometric analyses. The SPIN source eliminates the major
      ion losses of conventional ESI-mass spectrometry (MS) interfaces by placing the
      emitter in the first reduced pressure region of the instrument. The new ESI
      emitter array design developed in this study allows individualized sheath gas
      around each emitter in the array making it possible to generate an array of
      uniform and stable electrosprays in the subambient pressure (10 to 30 Torr)
      environment for the first time. The utility of the new emitter arrays was
      demonstrated by coupling the emitter array/SPIN source with a time of flight
      (TOF) mass spectrometer. The instrument sensitivity was compared under different
      ESI source and interface configurations including a standard atmospheric pressure
      single ESI emitter/heated capillary, single emitter/SPIN and multi-emitter/SPIN
      configurations using an equimolar solution of nine peptides. The highest
      instrument sensitivity was observed using the multi-emitter/SPIN configuration in
      which the sensitivity increased with the number of emitters in the array. Over an
      order of magnitude MS sensitivity improvement was achieved using multi
      emitter/SPIN compared with using the standard atmospheric pressure single ESI
      emitter/heated capillary interface.

PMID- 24676895
TI  - Low-energy collision-induced dissociation mass spectra of protonated p
      toluenesulfonamides derived from aliphatic amines.
AB  - Collision-induced fragmentation of protonated N-alkyl-p-toluenesulfonamides
      primarily undergo either an elimination of the amine to form CH3-(C6H4)-SO2(+)
      cation (m/z 155) or an alkene to form a cation for the protonated p
      toluenesulfonamide (m/z 172). To comprehend the fragmentation pathways, several
      deuterated analogs of N-decyl-p-toluenesulfonamides were prepared and evaluated.
      Hypothetically, two mechanisms, both of which involve ion-neutral complexes, can
      be envisaged. In one mechanism, the S-N bond fragments to produce an intermediate
      [sulfonyl cation/amine] complex, which dissociates to afford the m/z 155 cation
      (Pathway A). In the other mechanism, the C-N bond dissociates to produce a
      different intermediate complex. The fragmentation of this [p
      toluenesulfonamide/carbocation] complex eliminates p-toluenesulfonamide and
      releases the carbocation (Pathway B). Computations carried out by the Hartree
      Fock method suggested that the Pathway B is more favorable. However, a peak for
      the carbocation is observed only when the carbocation formed is relatively
      stable. For example, the spectrum of N-phenylethyl-p-toluenesulfonamide is
      dominated by the peak at m/z 105 for the incipient phenylethyl cation, which
      rapidly isomerizes to the remarkably stable methylbenzyl cation. The peaks for
      the carbocations are weak or absent in the spectra of most of N-alkyl-p
      toluenesulfonamides because alkyl carbocations, such as the decyl cation,
      rearrange to more stable secondary cations by 1,2-hydride and alkyl shifts. The
      energy freed is not dissipated, but gets internalized, causing the carbocation to
      dissociate either by transferring a proton to the sulfonamide or by releasing
      smaller alkenes to form smaller carbocations. The loss of the positional
      integrity in this way was proven by deuterium labeling experiments.

PMID- 24676896
TI  - The impact of new screen-detected and previously known type 2 diabetes on health
      related quality of life: a population-based study in Qingdao, China.
AB  - AIMS: To examine and compare health-related quality of life (HRQoL) in people
      with previously known diabetes, new screen-detected asymptomatic diabetes and
      people without diabetes. METHODS: HRQoL of 4,613 individuals who participated in
      a population-based cross-sectional diabetes survey in Qingdao, China, in 2009,
      was assessed using the 15D instrument. A Tobit regression model to estimate the
      effects of diabetes on HRQoL separate from effects of other health determinants
      was constructed. RESULTS: Among the surveyed population, 220 (4.8%) individuals
      had previously known diabetes and 531 (11.5%) individuals had new screen-detected
      diabetes, defined by fasting plasma glucose >=7.0 mmol/l and/or 2-h plasma
      glucose >=11.1 mmol/l. The age-, gender-, and BMI-adjusted mean 15D score of
      people without diabetes, with new screen-detected diabetes, and previously known
      diabetes was 0.975, 0.975, and 0.964, respectively, for urban and 0.971, 0.972,
      and 0.960, respectively, for rural participants. HRQoL overall and on all the
      dimensions (p < 0.05) except for hearing, eating, and speech was worse in the
      people with previously known diabetes compared to those with new screen-detected
      diabetes and those without diabetes. Compared to people without diabetes, people
      with new screen-detected diabetes were worse off on the dimension of usual
      activities (p < 0.05). After adjusting for comorbid diseases and other
      confounders, the impact of diabetes on reduced HRQoL was diminished. CONCLUSION:
      Health-related quality of life was impaired in people with previously known
      diabetes who had co-morbid conditions, but was largely unaltered in people with
      newly detected asymptomatic diabetes as compared to people without diabetes.

PMID- 24676897
TI  - Danish population-based reference data for the EORTC QLQ-C30: associations with
      gender, age and morbidity.
AB  - PURPOSE: General population reference data are useful in the interpretation of
      health-related quality of life (HRQoL) results, but for the European Organisation
      for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ
      C30), such data have been published for only seven countries. In 1992, Danish
      general population data were collected from women only for EORTC QLQ-C30 version
      1. Since no Danish reference data exists for men and women for the QLQ-C30
      version 3.0, the aims of this study were to generate such data and to investigate
      the associations between EORTC QLQ-C30 outcomes and age, gender and morbidity, as
      well as trends over time. METHODS: An age- and gender-stratified random sample of
      3,080 Danes was drawn from the Danish Civil Registration System. The EORTC QLQ
      C30 was administered electronically and by mail along with a short questionnaire
      concerning socio-demographics/morbidity. RESULTS: Responses were obtained from
      1,832 individuals (60.1% of 3,009 eligible individuals). Response rates varied
      across age groups, ranging from 41.9% (20-29 years) to 76.1% (70-79 years). The
      majority of subscales were strongly associated with age and morbidity. Between
      genders only small, but clinically meaningful and statistically significant
      differences were found in five out of fifteen scales. When comparing Danish women
      20 years ago and today, a tendency toward slightly improved function/reduced
      symptoms was observed, but the differences were small and statistically
      significant in only three subscales. CONCLUSION: This study is the first to
      present Danish general population reference values for the EORTC QLQ-C30 version
      3.0. Age and morbidity are important potential confounders that must be taken
      into account in HRQoL studies.

PMID- 24676898
TI  - A comparison of EQ-5D-3L population norms in Queensland, Australia, estimated
      using utility value sets from Australia, the UK and USA.
AB  - PURPOSE: To provide population norms for the EQ-5D-3L by age and gender based on
      a representative adult sample in Queensland, Australia; to assess differences in
      health-related quality of life by applying the Australian, UK and USA value sets
      to these data; and to assess differences in utility scores for key preventive
      health indicators. METHODS: A cross-sectional computer-assisted telephone
      interview survey (March-June 2011) with 5,555 adults. Respondents rated their
      impairment (none, moderate, severe problems) across five domains (mobility, self
      care, usual activities, pain and discomfort, anxiety or depression) using the
      validated EQ-5D-3L health-related quality of life instrument. Utility score
      indexes were derived using the Australian, UK and USA value sets. RESULTS: Forty
      per cent of adults reported pain and discomfort while 3% indicated problems with
      self-care. Approximately one in six had limitations with mobility, usual
      activities or anxiety or depression. The three value sets performed similarly in
      discriminating differences based on most characteristics, and clinically
      meaningful differences were seen for age, body weight, physical activity and
      daily smoking. There were no differences in utility scores for gender.
      CONCLUSIONS: This is the first study to report general population findings for
      the Australian EQ-5D-3L value set. Overall, the Australian value set performed
      comparably with other value sets commonly used in the Australian population;
      however, differences were observed. Results will enable further refinement to
      health and economic studies in an Australian-specific context.

PMID- 24676899
TI  - Monitoring collagen synthesis in fibroblasts using fluorescently labeled tRNA
      pairs.
AB  - There is a critical need for techniques that directly monitor protein synthesis
      within cells isolated from normal and diseased tissue. Fibrotic disease, for
      which there is no drug treatment, is characterized by the overexpression of
      collagens. Here, we use a bioinformatics approach to identify a pair of glycine
      and proline isoacceptor tRNAs as being specific for the decoding of collagen
      mRNAs, leading to development of a FRET-based approach, dicodon monitoring of
      protein synthesis (DiCoMPS), that directly monitors the synthesis of collagen.
      DiCoMPS aimed at detecting collagen synthesis will be helpful in identifying
      novel anti-fibrotic compounds in cells derived from patients with fibrosis of any
      etiology, and, suitably adapted, should be widely applicable in monitoring the
      synthesis of other proteins in cells.

PMID- 24676900
TI  - Enrichment and characterization of cancer stem-like cells from a cervical cancer
      cell line.
AB  - Cancer stem cells (CSCs) are proposed to be responsible for tumor recurrence,
      metastasis and the high mortality rate of cancer patients. Isolation and
      identification of CSCs is crucial for basic and preclinical studies. However, as
      there are currently no universal markers for the isolation and identification of
      CSCs in any type of cancer, the method for isolating CSCs from primary cancer
      tissues or cell lines is costly and ineffective. In order to establish a reliable
      model of cervical cancer stem cells for basic and preclinical studies, the
      present study was designed to enrich cervical cancer CSCs using a nonadhesive
      culture system and to characterize their partial stemness phenotypes. Human
      cervical cancer cells (HeLa) were cultured using a nonadhesive culture system to
      generate tumor spheres. Their stemness characteristics were investigated through
      colony formation, tumor sphere formation, self-renewal, toluidine blue staining,
      chemoresistance, invasion assays, reverse transcription-polymerase chain
      reaction, immunofluorescence staining of putative stem cell markers, including
      octamer-binding transcription factor 4, SRY-box 2 and aldehyde dehydrogenase 1
      family, member A1, and adipogenic differentiation induction. Typical tumor
      spheres were formed within 5-7 days under this nonadhesive culture system.
      Compared with the adherent parental HeLa cells, the colony formation capacity,
      self-renewal potential, light cell population, cell invasion, chemoresistance and
      expression of putative stem cell markers of the tumor sphere cells increased
      significantly, and a subpopulation of tumor sphere cells were induced into
      adipogenic differentiation. Using the nonadhesive culture system, a reliable
      model of cervical cancer stem cells was established, which is inexpensive,
      effective and simple compared with the ultra-low attachment serum free culture
      method. The stemness characteristics of the tumor sphere HeLa cells mirrored the
      CSC phenotypes. This CSC model may be useful for basic and preclinical studies of
      cervical cancer and other types of cancer.

PMID- 24676902
TI  - Cancer and thrombosis--an update.

PMID- 24676901
TI  - Complete regression and systemic protective immune responses obtained in B16
      melanomas after treatment with LTX-315.
AB  - Malignant melanoma is the most aggressive and deadliest form of skin cancer due
      to its highly metastatic potential, which calls for new and improved therapies.
      Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in
      most species, in which they play a significant role in the first line of defense
      against pathogens, and several CAPs have shown promising potential as novel
      anticancer agents. Structure-activity relationship studies on the CAP bovine
      lactoferricin allowed us to de novo design short chemically modified lytic
      anticancer peptides. In the present study, we investigated the in vivo antitumor
      effects of LTX-315 against intradermally established B16 melanomas in syngeneic
      mice. Intratumoral administration of LTX-315 resulted in tumor necrosis and the
      infiltration of immune cells into the tumor parenchyma followed by complete
      regression of the tumor in the majority of the animals. LTX-315 induced the
      release of danger-associated molecular pattern molecules such as the high
      mobility group box-1 protein in vitro and the subsequent upregulation of
      proinflammatory cytokines such as interleukin (IL) 1beta, IL6 and IL18 in vivo.
      Animals cured by LTX-315 treatment were protected against a re-challenge with
      live B16 tumor cells both intradermally and intravenously. Together, our data
      indicate that intratumoral treatment with LTX-315 can provide local tumor control
      followed by protective immune responses and has potential as a new
      immunotherapeutic agent. 

PMID- 24676903
TI  - Current status of use of erythropoietic agents in cancer patients.
AB  - Anemia is frequently observed in cancer patients and can cause symptoms and
      result in red cell transfusions. The erythropoiesis stimulating agents (ESAs)
      have been shown to increase hemoglobin levels and reduce transfusion requirements
      in anemic subjects with cancer who are receiving chemotherapy. Initially, these
      benefits motivated broad use of the ESAs in oncology. Over the past 10 years,
      recognition of the adverse events that can be associated with ESA use in these
      patients, particularly venous thrombosis, has resulted in a rethinking of the
      issue of who are the correct candidates for treatment. Different health care
      systems have come to different conclusions based upon the available data and
      additional data are still being generated. This article will review the data
      concerning the safety of ESAs in cancer patients, including the results of
      additional trials published in the past 2 years. This will include a discussion
      of the potential of ESAs to impact tumor progression or survival. Thrombosis
      remains the most important and best documented adverse event associated with ESA
      therapy in oncology. The mechanism(s) through which ESAs alter thrombosis risk
      are still very poorly understood. 

PMID- 24676904
TI  - Dietary soy isoflavones increased hepatic protein disulfide isomerase content and
      suppressed its enzymatic activity in rats.
AB  - Protein disulfide isomerase (PDI) is a multifunctional protein and plays
      important roles in protein folding, triglyceride transfer, insulin degradation,
      and thyroid hormone transportation. This study examined the modulation of PDI
      expression by soy consumption using rat as a model. Sprague-Dawley male and
      female rats at 50 days (d) of age were fed diets containing either 20% casein or
      alcohol-washed soy protein isolate (SPI, containing 50 mg isoflavones (ISFs)/kg
      diet) or SPI plus ISF (250 mg/kg diet) and mated at age of 120 d. The offspring
      (F1) were fed the same diets as their parents. Addition of ISF to SPI diet
      markedly increased PDI protein content in the liver and testis of the adult rats
      compared with the casein or SPI diet. PDI mRNA abundance in the liver and protein
      content in the brain, thyroid, heart, and uterus were unchanged by the diets. Two
      dimensional Western blot showed that the rats fed diets containing SPI had a
      diminished hepatic PDI protein with an isoelectric point (pI) of 6.12, a
      dephosphorylated form, compared with the rats fed diets containing either casein
      or SPI with supplemental ISF. Soy ISF added into SPI diet remarkably suppressed
      hepatic PDI activity of the rats compared with the casein diet. Moreover, soy ISF
      dose-dependently increased PDI and thyroid hormone receptor (TR) beta protein
      content, whereas reduced TR DNA binding ability in human hepatocytes. Overall,
      this study shows that soy ISF increased hepatic PDI protein content, but addition
      of ISF into SPI diet inhibited its enzymatic activities and this effect may be
      mediated through a post-transcriptional mechanism.

PMID- 24676905
TI  - VER-155008, a small molecule inhibitor of HSP70 with potent anti-cancer activity
      on lung cancer cell lines.
AB  - Lung cancer is the most common malignancy and exhibits significant morbidity and
      mortality worldwide. Among all lung cancer subtypes, non-small-cell lung cancer
      (NSCLC) accounts for the majority of all lung cancer cases. Although there have
      been intensive investigations on the underlying mechanism of NSCLC development
      and progression, the exact molecular basis is not well understood. Further
      insights on important molecular regulators of lung cancer are needed for
      development of novel therapeutics. The heat shock protein (HSP) family is a group
      of molecular chaperones that assist in protein folding, modification, and
      transportation. Different HSPs are essential for tumor cell survival by binding
      diverse client proteins and regulating homeostasis. In the current study, we
      sought to characterize HSP70 and HSP90 as potent regulators of NSCLC growth. Our
      results indicate that differential expression of HSP70 is associated with the
      malignant phenotype of NSCLC cell lines and plays an important regulatory role in
      NSCLC cell proliferation. Moreover, a specific inhibitor of HSP70, VER-155008
      significantly inhibits NSCLC proliferation and cell cycle progression. We showed
      that this effect is largely abolished by HSP70 overexpression, indicating that
      the inhibitory effect of VER-155008 on cell growth is specifically through HSP70
      inhibition. In addition, 17-AAD, an inhibitor of HSP90, exerts a potent
      synergistic effect on NSCLC proliferation with VER-155008. We also observed that
      inhibition of HSP70 by VER-155008 can sensitize A549 cells to ionizing radiation.
      These data provide proof-of-principle that VER-155008 can be a good candidate for
      NSCLC treatment and HSP machinery is a good target for developing NSCLC
      therapeutics. 

PMID- 24676906
TI  - Decreased glutathione and elevated hair mercury levels are associated with
      nutritional deficiency-based autism in Oman.
AB  - Genetic, nutrition, and environmental factors have each been implicated as
      sources of risk for autism. Oxidative stress, including low plasma levels of the
      antioxidant glutathione, has been reported by numerous autism studies, which can
      disrupt methylation-dependent epigenetic regulation of gene expression with
      neurodevelopmental consequences. We investigated the status of redox and
      methylation metabolites, as well as the level of protein homocysteinylation and
      hair mercury levels, in autistic and neurotypical control Omani children, who
      were previously shown to exhibit significant nutritional deficiencies in serum
      folate and vitamin B12. The serum level of glutathione in autistic subjects was
      significantly below control levels, while levels of homocysteine and S
      adenosylhomocysteine were elevated, indicative of oxidative stress and decreased
      methionine synthase activity. Autistic males had lower glutathione and higher
      homocysteine levels than females, while homocysteinylation of serum proteins was
      increased in autistic males but not females. Mercury levels were markedly
      elevated in the hair of autistic subjects vs. control subjects, consistent with
      the importance of glutathione for its elimination. Thus, autism in Oman is
      associated with decreased antioxidant resources and decreased methylation
      capacity, in conjunction with elevated hair levels of mercury.

PMID- 24676907
TI  - Cardiomyocyte differentiation induced in cardiac progenitor cells by cardiac
      fibroblast-conditioned medium.
AB  - Our previous study showed that after being treated with 5-azacytidine, Nkx2.5(+)
      human cardiac progenitor cells (CPCs) derived from embryonic heart tubes could
      differentiate into cardiomyocytes. Although 5-azacytidine is a classical agent
      that induces myogenic differentiation in various types of cells, the drug is
      toxic and unspecific for myogenic differentiation. To investigate the possibility
      of inducing CPCs to differentiate into cardiomyocytes by a specific and non-toxic
      method, CPCs of passage 15 and mesenchymal stem cells (MSCs) were treated with
      cardiac ventricular fibroblast-conditioned medium (CVF-conditioned medium).
      Following this treatment, the Nkx2.5(+) CPCs underwent cardiomyogenic
      differentiation. Phase-contrast microscopy showed that the morphology of the
      treated CPCs gradually changed. Ultrastructural observation confirmed that the
      cells contained typical sarcomeres. The expression of cardiomyocyte-associated
      genes, such as alpha-cardiac actin, cardiac troponin T, and beta-myosin heavy
      chain (MHC), was increased in the CPCs that had undergone cardiomyogenic
      differentiation compared with untreated cells. In contrast, the MSCs did not
      exhibit changes in morphology or molecular expression after being treated with
      CVF-conditioned medium. The results indicated that Nkx2.5(+) CPCs treated with
      CVF-conditioned medium were capable of differentiating into a cardiac phenotype,
      whereas treated MSCs did not appear to undergo cardiomyogenic differentiation.
      Subsequently, following the addition of Dkk1 and the blocking of Wnt signaling
      pathway, CVF-conditioned medium-induced morphological changes and expression of
      cardiomyocyte-associated genes of Nkx2.5(+) CPCs were inhibited, which indicates
      that CVF-conditioned medium-induced cardiomyogenic differentiation of Nkx2.5(+)
      CPCs is associated with Wnt signaling pathway. In addition, we also found that
      the activation of Wnt signaling pathway was accompanied by higher expression of
      GATA-4 and the blocking of the pathway inhibited the expression of GATA-4 in CVF
      conditioned medium-incubated Nkx2.5(+) CPCs. This finding suggests that Wnt
      signaling pathway may alter GATA-4 expression and activate the cardiogenic
      program in the regulation of differentiation. In conclusion, Nkx2.5(+) CPCs have
      enormous potential for cardiomyogenic differentiation and the CVF-conditioned
      medium specifically induces CPCs to differentiate into a cardiac phenotype. Wnt
      signaling pathway is involved in CVF-conditioned medium-induced cardiomyogenic
      differentiation of Nkx2.5(+) CPCs.

PMID- 24676908
TI  - Promising anticancer activity of a lichen, Parmelia sulcata Taylor, against
      breast cancer cell lines and genotoxic effect on human lymphocytes.
AB  - Plants are still to be explored for new anti-cancer compounds because overall
      success in cancer treatment is still not satisfactory. As a new possible source
      for such compounds, the lichens are recently taking a great attention. We,
      therefore, explored both the genotoxic and anti-growth properties of lichen
      species Parmelia sulcata Taylor. The chemical composition of P. sulcata was
      analyzed with comprehensive gas chromatography-time of flight mass spectrometry.
      Anti-growth effect was tested in human breast cancer cell lines (MCF-7 and MDA-MB
      231) by the MTT and ATP viability assays, while the genotoxic activity was
      studied by assays for micronucleus, chromosomal aberration and DNA fragmentation
      in human lymphocytes culture. Cell death modes (apoptosis/necrosis) were
      morphologically assessed. P. sulcata inhibited the growth in a dose-dependent
      manner up to a dose of 100 MUg/ml and induced caspase-independent apoptosis. It
      also showed genotoxic activity at doses (>125 MUg/ml) higher than that required
      for apoptosis. These results suggest that P. sulcata may induce caspase
      independent apoptotic cell death at lower doses, while it may be genotoxic at
      relatively higher doses. 

PMID- 24676909
TI  - Effect of freezing on the release rate of gentamicin palmitate and gentamicin
      sulfate from bone tissue.
AB  - In this study we evaluated gentamicin palmitate salt and gentamicin sulfate salt
      mixed with bone chips after storage at -80 degrees C. Different concentration
      rates of gentamicin sulfate and gentamicin palmitate were mixed with human bone
      chips and stored for 1-6 months at -80 degrees C. Nonstored samples were used as
      control. The release of the antibiotics from the bone was carried out in
      phosphate-buffered saline. Antibiotic concentrations in the elutions were
      determined with microbiological agar diffusion assay using Bacillus subtilis.
      Susceptibility tests were carried out using Staphylococci strains. The rate of
      gentamicin base (GB) released from bone was similar for all gentamicin salts and
      all storage conditions. The elutions released were efficient on reducing S.
      aureus and S. epidermidis CFU during all storage time. In resume, the capacity of
      bone grafts to act as gentamicin carriers has been confirmed in this study. GS +
      GP showed equivalent efficacy against S. aureus and S. epidermidis compared with
      GS pure. The lower delivery rate of GS + GP, related to its affinity with fat
      tissue can be an advantage for longer release times, increasing the local
      protection against infections. Storage at -80 degrees C does not interfere on the
      gentamicin salts activity used.

PMID- 24676910
TI  - Diet and the bone marrow niche for stem cell recruitment.

PMID- 24676912
TI  - Theoretical performance of non-invasive prenatal testing for chromosome
      imbalances using counting of cell-free DNA fragments in maternal plasma.
AB  - OBJECTIVE: The aim of this study was to calculate the theoretical performance of
      non-invasive prenatal testing based on counting methods. METHODS: The
      calculations were based on Gaussian distributions of the percent cell-free DNA
      from selected chromosome regions in affected and normal pregnancies. The means
      were derived from the relative genomic size of the chromosome region and the
      fetal fraction. The standard deviations were derived from the bivariate
      distributions of proportional counts. Depth of sequencing was varied from
      50,000,000 to 100,000 and fetal fraction from 20% to 3%. Detection rate was
      estimated for a fixed 0.13% false-positive rate. RESULTS: When either depth or
      fetal fraction is high, expected Down syndrome screening detection rates are
      high. However, when fetal fraction is low, deeper sequencing is required to
      obtain high detection rates. For microdeletion and microduplication screening,
      deeper sequencing is routinely required to consistently achieve high detection
      rates. There are small differences in the ability to detect a microdeletion
      compared with a duplication of the same size. CONCLUSION: While the theoretical
      calculations do not necessarily reflect the performance of currently available
      non-invasive prenatal testing tests, it confirms that fetal fraction is a key
      factor. Efficacy can be substantially altered depending on the abnormality under
      investigation and the depth of sequencing.

PMID- 24676911
TI  - Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse
      colonic interstitial cells of Cajal.
AB  - Cyclic guanosine 3',5'-monophosphate (cGMP) inhibited the generation of pacemaker
      activity in interstitial cells of Cajal (ICCs) from the small intestine. However,
      cGMP role on pacemaker activity in colonic ICCs has not been reported yet. Thus,
      we investigated the role of cGMP in pacemaker activity regulation by colonic
      ICCs. We performed a whole-cell patch-clamp and Ca(2+) imaging in cultured ICCs
      from mouse colon. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor
      of guanylate cyclase) increased the pacemaker potential frequency, whereas
      zaprinast (an inhibitor of phosphodiesterase) and cell-permeable 8-bromo-cGMP
      decreased the pacemaker potential frequency. KT-5823 (an inhibitor of protein
      kinase G [PKG]) did not affect the pacemaker potential. L-N(G)-nitroarginine
      methyl ester (L-NAME, an inhibitor of nitric oxide [NO] synthase) increased the
      pacemaker potential frequency, whereas (+/-)-S-nitroso-N-acetylpenicillamine
      (SNAP, a NO donor) decreased the pacemaker potential frequency. Glibenclamide (an
      ATP-sensitive K(+) channel blocker) did not block the effects of cell-permeable 8
      bromo-cGMP and SNAP. Recordings of spontaneous intracellular Ca(2+) ([Ca(2+)]i)
      oscillations revealed that ODQ and L-NAME increased [Ca(2+)]i oscillations. In
      contrast, zaprinast, 8-bromo cGMP, and SNAP decreased the [Ca(2+)]i oscillations.
      Basal cGMP levels regulate the resting pacemaker potential frequency by the
      alteration on Ca(2+) release via a PKG-independent pathway. Additionally, the
      endogenous release of NO seems to be responsible maintaining basal cGMP levels in
      colonic ICCs.

PMID- 24676913
TI  - [Not Available].

PMID- 24676914
TI  - [Not Available].

PMID- 24676915
TI  - [Not Available].
AB  - Methods of quality management and quality assurance aim at improving medical
      facilities, procedures and services to benefit patients and avoid potential harm.
      It is prudent to call these measures "secondary technologies" because they are
      used to optimize the so-called "primary technologies" used in medicine such as
      diagnosis, therapy, rehabilitation and counseling. However, in light of the
      considerable efforts and high costs associated with quality assurance measures,
      it is important that these measures be subject to critical review. Like all other
      procedures or technologies used in health care, quality assurance measures must
      be reviewed with respect to their effects and costs prior to and during
      implementation. The primary issue of such pre-evaluation and re-evaluation is to
      analyze whether the benefits justify the costs and then to define how quality
      assurance measures can be used to help improve the outcomes of health care
      services. Quality assurance measures must focus on health care priorities. They
      should be limited to common and serious health problems, the core services of the
      different health care providers and to high-risk interventions. Quality assurance
      must contribute primarily to the health of patients and protect them from
      avoidable harm. Quality management must be patient and outcome oriented and
      should uphold the ideal of the responsible and informed patient, whose dignity
      and autonomy must be respected. Above all, strengthening the position of health
      care users requires comprehensive, comprehensible and easily accessible
      information on the targets and outcomes of quality management. This is a basic
      requirement for setting up a quality-oriented information culture in the health
      care system and should be given high priority. 

PMID- 24676916
TI  - [Not Available].

PMID- 24676917
TI  - [Not Available].
AB  - The Association of the Scientific Medical Societies in Germany (AWMF) established
      a national guideline-programme respecting the specific conditions of the German
      health-care system as well as fulfilling the demands of clinical research. It
      consists of a three-level concept for guideline development and an implementation
      system. The three-level concept assumes a continuous process of development and
      quality improvement of guidelines. At level three, guidelines have to fulfill
      five criteria of systematic development: consensus (presupposed application of
      formal techniques and participation of all relevant stakeholders), logical
      analysis (clinical algorithms), evidence (based on best available evidence
      derived from comprehensive, systematic reviews and linking all recommendations
      explicitly to the evidence), decision analysis and outcome analysis (using
      epidemiologic, effectiveness, pharmacologic, psychometric, economic studies and
      qualitative methods for identifying the true endpoint). The implementation system
      is based on four components: definite guideline groups within the scientific
      societies, conceptualised quality improvement of guidelines, continuous medical
      education and systematic evaluation. The establishment of this system has induced
      a change: the process of developing top-level guidelines has become uniform and
      there is a strong trend towards quality improvement. 75 evidence- and consensus-
      based guidelines (level two and three) have already been published. The
      scientific medical societies have indicated their motivation to continue the
      program by formulating 75 prior conditions for which top-level guidelines shall
      be developed in the near future. 

PMID- 24676918
TI  - [Not Available].
AB  - Quality assurance is a crucial factor in legitimizing decisions about investments
      in sectors of the health care system such as disease prevention and health
      promotion. Conditions necessary for effective and efficient health promotion are
      presented, and ways to improve these conditions are discussed. To show how
      national campaigns can successfully initiate societal learning processes, the
      authors describe the case of aids education in Germany. Was it just a special
      case, or was it an example of how effective disease prevention can be? Can it be
      a model for other prevention campaigns? 

PMID- 24676919
TI  - [Not Available].
AB  - Within the demonstration project "Quality Management in Hospitals" (DemoProQM),
      44 hospitals, organised in ten collaborative project groups, were supported by
      the German Ministry of Health from 1998 to 2001 in their methods for implementing
      total quality management. Their activities were monitored and evaluated by a
      staff of scientists and experts in the field. The main intention of the DemoProQM
      project was the implementation of quality management with special attention to
      patients and staff concerns, including all professions, hierarchies and hospital
      units. The second objective was to show other hospitals successful methods of
      implementing quality management and to demonstrate its benefits with special
      regards to the aspects of quality, economy and competition. To achieve these
      aims, the participating hospitals created adequate quality management structures
      and defined a quality policy as well as quality goals. In quality improvement
      projects, interprofessional teams tried to achieve these quality goals using the
      well-known methods of quality management. The successes and problems experienced
      by the participating hospitals are reported below. 

PMID- 24676920
TI  - [Not Available].
AB  - Quality management has been one of the main functions of the KV for decades.
      Using the KV Hessen as an example, the range of methods used, their areas of
      application and the underlying concepts as well as the legal framework are
      illustrated. It is evident that the strucural approach of the past is being
      complemented by process and outcome orientated methods. Impending major
      developments in the German health system and their significance for quality
      assurance are discussed. Key factors in this process will be new forms of
      remuneration and technical innovations. 

PMID- 24676921
TI  - [Not Available].
AB  - Since the 1990ies, the field of Medical Rehabilitation in Germany, which is a
      largely independent part of the German health care system, has undergone a
      modification process oriented towards various objectives. An optimized
      orientation towards both user related attributes and result related aspects has
      been the object of endeavors, manifested in the introduction of quality assurance
      programs and intensified rehabilitation-scientific research. The quality
      assurance program created by the medical rehabilitation section of the federal
      statutory pension insurance providers (the so-called 5-point program) forms a
      central component of this new orientation. The conceptualization of appropriate
      initiatives for the medical rehabilitation sections of the health insurance
      organizations, for providers of child rehabilitation, and the field of ambulatory
      rehabilitation will take place within the immediate future. 

PMID- 24676922
TI  - [Not Available].
AB  - In Germany, the database on falls among children (<15 years) is insufficient
      because there is no systematic, population-based monitoring of injuries according
      to location, type and mechanism. This analysis will compile relevant data on fall
      injuries among children in Germany and define risk groups, risk factors and
      typical accident mechanisms according to the frequency and severity of fall
      injuries. RESULTS: In 1998, 31 children (<15 years) (N=655) died through falls,
      in most cases by falling from a building (n=8). Around 700,000 children are
      estimated to have required medical treatment for falls, approx. 120,000 of them
      being hospitalized. Fall injuries show an age- and environment-specific accident
      pattern. Most of the falls among infants and toddlers are from changing tables,
      children's beds, high chairs and stairs. Among school-age children, falls occur
      most frequently at school (during break and physical education lessons) and
      during leisure activities (skating, cycling). These facts should form the basis
      for prevention measures targeting behaviour and health conditions.

PMID- 24676923
TI  - Biological Correlates of Sexual Transmission of HIV Practical Consequences and
      Potential Targets for Public Health : Practical Consequences and Potential
      Targets for Public Health.
AB  - The probability of sexual transmission of HIV depends on the infectiousness of
      the index case and the susceptibility of the sexual contact. The risk of HIV
      transmission is heterogeneous and may be greatest during the initial sexual
      contacts in a steady partnership. Several factors, including systemic and mucosal
      acquired protective immune-response might be responsible for the apparent
      decrease of per-sex-act risk of transmission in a given partnership over time.
      Biological studies can be used to better understand the complex information
      obtained by epidemiological surveys. The infectiousness of HIV depends on the
      inoculum, and virologic factors. The genital tract viral load of the index case
      is likely the most important determinant of transmission. At the population
      level, interventions that reduce the genital shedding of HIV by reducing systemic
      blood viral load and/or local inflammatory processes are likely to have a
      beneficial impact on HIV incidence. Antiretroviral drugs are likely to reduce
      sexual transmission of HIV. However, these drugs may not all prove equally.
      Compartmentalized HIV replication in the male and female genital tract have been
      observed. Treatment with antiretroviral drugs that poorly penetrate the genital
      tract harbour the risk of local production and spread of resistant viruses. In
      addition, increased risk taking behaviour could offset the benefits of reduced
      probability of transmission at the population level. Biological data about HIV
      transmission must be used to inform public health policies and optimize HIV
      prevention strategies. 

PMID- 24676924
TI  - Can We Measure STD Risk Behavior or STD as Surrogates for HIV risk? Presented at
      the International Congress of Sexually Transmitted Infections (ISSTDR/IUSTI)
      2001, Berlin : Presented at the International Congress of Sexually Transmitted
      Infections (ISSTDR/IUSTI) 2001, Berlin.
AB  - There is great interest in the development of surrogate measures for HIV
      infection that could be used in intervention trials. The sample size needed to
      detect a change in HIV incidence may be 10 times larger than the sample needed to
      detect a change in STD (sexually transmitted disease) incidence, and 200 times
      larger than that needed to detect a change in behavior. We do not know how
      accurately we can measure sexual behavior. We know many factors that influence
      responses to questions. Although behavior is clearly associated with STD and HIV,
      acquisition of disease requires sexual contact with an infected person.
      Questionnaires have been unable to satisfactorily measure the prevalence of
      infection in a person's partners. Behavior is not a good surrogate for STD or HIV
      because behavior change interventions can change question answering behavior, and
      people have safe sex with risky partners and risky sex with safe partners. STD
      are not a good surrogate for HIV if the intervention influences STD treatment, if
      protective behaviors such as condom use influence some STD more than others, or
      if HIV specific interventions are used, such as deciding to have sex without a
      condom if a partner has a negative HIV test. 

PMID- 24676926
TI  - [Not Available].

PMID- 24676925
TI  - Synergistic effects of STI Control and HIV prevention Presented at the
      International Congress of Sexually Transmitted Infections (ISSTDR/IUSTI) 2001,
      Berlin : Presented at the International Congress of Sexually Transmitted
      Infections (ISSTDR/IUSTI) 2001, Berlin.
AB  - Provision of early and effective treatment of STD impacts on HIV transmission by
      shortening the duration of a biological cofactor for HIV transmission, which can
      lead to reduced infectiousness in an HIV positive person or reduced
      susceptibility in an HIV negative person. In addition, offering good quality STD
      services, integrated into the existing healthcare centres or set up as special
      programmes for hard-to-reach populations, such as young people or sex workers,
      provides unique opportunities to offer and reinforce prevention messages. This
      care-prevention synergy has been thoroughly documented in projects involving sex
      workers in the Democratic Republic (RD) of Congo and Cote d'Ivoire, where
      integrated packages of services have facilitated getting in touch with a large
      number of women who never sought STD care before, and reinforced the preventive
      messages, leading to a dramatic decline in new HIV infections over the years.
      Currently, multiple integrated reproductive service packages, including STD care
      for youth groups, are being put in place and their synergistic impact on HIV
      prevention is being investigated. 

PMID- 24676927
TI  - [Not Available].

PMID- 24676928
TI  - [Not Available].

PMID- 24676929
TI  - [Not Available].

PMID- 24676930
TI  - An overview of amines as nutritional supplements to counteract cancer cachexia.
AB  - Cancer cachexia is a complex multifactorial syndrome characterized by loss of
      skeletal muscle mass (with or without loss of fat mass) that cannot be fully
      reversed by conventional nutritional support and leads to progressive functional
      impairment. Recently, some amino acids and other amine dietary supplements have
      been highlighted in medical field due to positive effects upon diseases evolving
      skeletal muscle atrophy. Therefore, the aim of this brief review is to discuss
      the putative application of amines as dietary supplements to counteract skeletal
      muscle wasting on cancer cachexia. Specifically, we focus in two nutritional
      supplements: (1) branched-chain amino acids (BCAAs) and (2) creatine. Both BCAAs
      and creatine may attenuate proteolysis and enhance proteins synthesis in skeletal
      muscle. Although more experimental studies and clinical trials are still
      necessary to elucidate this therapeutic application, several evidences have
      demonstrated that amines supplementation is a promising coadjuvant treatment to
      cancer cachexia. 

PMID- 24676931
TI  - PAR-1 antagonist vorapaxar favorably improves global thrombotic status in
      patients with coronary disease.
AB  - To assess the effect of vorapaxar on global thrombotic and thrombolytic status.
      The propensity for thrombus formation is determined by the balance between
      prothrombotic factors and endogenous thrombolysis. Impaired thrombolytic status
      increases cardiovascular risk. Vorapaxar is a novel, oral, protease-activated
      receptor-1 antagonist that inhibits thrombin-induced platelet activation. In the
      TRACER and TRA 2 degrees P-TIMI 50 studies, patients with acute coronary
      syndromes and established atherosclerosis were randomized to vorapaxar 2.5 mg
      daily or placebo, in addition to standard care. In 57 patients enrolled in a
      single center, blood was tested with the point-of-care global thrombosis test, on
      and off treatment. This automated test employs non-anticoagulated blood to assess
      thrombotic and thrombolytic status, measuring the time required to form a shear
      induced thrombus under physiological conditions (occlusion time, OT), and
      subsequently, the time to achieve endogenous lysis of the thrombus (lysis time,
      LT). Patients on vorapaxar exhibited longer OT on vs. off treatment [median 561 s
      (interquartile range 422-654) vs. 372 s(338-454), P = 0.003] and shorter LT on
      treatment than off [1,158 s(746-1,492) vs. 1,733 s(1,388-2,230), P = 0.016].
      Patients on placebo showed no difference in OT [419 s(343-514) vs. 411 s(346
      535), P = 0.658] or LT [1,236 s(985-1,594) vs. 1,400 s(1,092-1,686), P = 0.524]
      on and off treatment. During treatment, OT was longer in patients taking
      vorapaxar [561 s(422-654) vs. 419 s(343-514), P = 0.009], but LT was similar in
      vorapaxar and placebo arms [1,158 s(746-1,492) vs. 1,236 s(985-1,594), P =
      0.277]. Vorapaxar prolongs OT and shortens LT, with favorable effects on
      thrombotic and thrombolytic status. In addition to its antiplatelet effect,
      vorapaxar may enhance endogenous thrombolysis, which is frequently impaired in
      coronary disease. 

PMID- 24676932
TI  - Autophagy is modulated in human neuroblastoma cells through direct exposition to
      low frequency electromagnetic fields.
AB  - In neurogenerative diseases, comprising Alzheimer's (AD), functional alteration
      in autophagy is considered one of the pathological hallmarks and a promising
      therapeutic target. Epidemiological investigations on the possible causes
      undergoing these diseases have suggested that electromagnetic fields (EMF)
      exposition can contribute to their etiology. On the other hand, EMF have
      therapeutic implications in reactivating neuronal functionality. To partly
      clarify this dualism, the effect of low-frequency EMF (LF-EMF) on the modulation
      of autophagy was investigated in human neuroblastoma SH-SY5Y cells, which were
      also subsequently exposed to Abeta peptides, key players in AD. The results
      primarily point that LF-EMF induce a significant reduction of microRNA 30a (miR
      30a) expression with a concomitant increase of Beclin1 transcript (BECN1) and its
      corresponding protein. Furthermore, LF-EMF counteract the induced miR-30a up
      regulation in the same cells transfected with miR-30a mimic precursor molecules
      and, on the other side, rescue Beclin1 expression after BECN1 siRNA treatment.
      The expression of autophagy-related markers (ATG7 and LC3B-II) as well as the
      dynamics of autophagosome formation were also visualized after LF-EMF exposition.
      Finally, different protocols of repeated LF-EMF treatments were assayed to
      contrast the effects of Abeta peptides in vitro administration. Overall, this
      research demonstrates, for the first time, that specific LF-EMF treatments can
      modulate in vitro the expression of a microRNA sequence, which in turn affects
      autophagy via Beclin1 expression. Taking into account the pivotal role of
      autophagy in the clearance of protein aggregates within the cells, our results
      indicate a potential cytoprotective effect exerted by LF-EMF in neurodegenerative
      diseases such as AD. J. Cell. Physiol. 229: 1776-1786, 2014. (c) 2014 Wiley
      Periodicals, Inc. 

PMID- 24676933
TI  - Soluble VEGFR1 concentration in the serum of patients with colorectal cancer.
AB  - PURPOSE: VEGFR is involved in complex biological processes, including
      inflammation and cancer development, progression and metastasis. Many proteins,
      including VEGFR, are proteolytically released from the surface of cells by a
      process known as ectodomain shedding. The aim of this study was to assess the
      expression of soluble VEGFR1 (sVEGFR1) in the serum of patients with colorectal
      cancer (CRC). METHODS: Sixty-two serum samples from healthy controls and 88
      samples from patients with different stages of CRC were included in this study.
      The total protein concentration (TPC) was measured using a Bio-Rad protein assay,
      and the expression and concentration of sVEGFR1 was determined by a Western blot
      analysis and enzyme-linked immunosorbent assay, respectively. RESULTS: No
      significant difference in the serum TPC of patients with and without CRC was
      seen. The relative s-VEGFR1 expression and concentration of sVEGFR1 in the serum
      of patients with CRC were significantly increased compared to those in controls
      (P < 0.001). CONCLUSIONS: The results of this study suggest that VEGFR1 shedding
      may provide a reliable and practical indicator of the malignant potential, tumor
      progression and overall tumor burden. The findings also suggest that sVEGFR1
      might be involved in the pathophysiology of CRC, and the detection of serum
      sVEGFR1 may be useful in classifying CRC.

PMID- 24676934
TI  - Bilateral pseudoangiomatous stromal hyperplasia tumors in axillary male
      gynecomastia: report of a case.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferation of
      breast stromal cells with a complex pattern of interanastomosing spaces lined by
      myofibroblasts. The exact etiology is still unknown, but a proliferative response
      of myofibroblasts to hormonal stimuli has been postulated. PASH is a relatively
      common incidental finding in breast tissue removed for other reasons and rarely
      manifests as a localized mass. Fewer than 150 cases of tumoral PASH have been
      reported since it was first described in 1986. Although PASH tends to grow over
      time, most lesions are cured by surgical excision and the prognosis is excellent.
      We report an unusual case of bilateral axillary tumoral PASH in a 44-year-old
      man. Awareness of this disease is important when considering the differential
      diagnosis of axillary masses. To our knowledge, only one other case of unilateral
      axillary tumoral PASH in a male patient has been described in English and this is
      the first case of PASH occurring in male bilateral axillary gynecomastia.

PMID- 24676935
TI  - Short- and long-term responses and recovery of mussels Mytilus edulis exposed to
      heavy fuel oil no. 6 and styrene.
AB  - Biomarkers have the potential to be used to assess the impact of anthropogenic
      discharges in marine waters. We have used a suite of biomarkers spanning from
      enzymatic to histopathological alterations and general stress responses to assess
      the short- and long-term impact on mussels Mytilus edulis of heavy fuel oil no. 6
      and styrene. Mussels were exposed for 5 months, with a refilling of the exposure
      system, to a water soluble fraction of heavy fuel and, then, kept for a month in
      clean water for recovery. In a second experiment, mussels were exposed to styrene
      for 19 days and maintained in clean water for up to 4 months. Chemical body
      tissue levels reflected the weathering processes of these compounds. Acyl-CoA
      oxidase activity was induced in oil-exposed mussels after refilling, whereas
      styrene inhibited it after 19 days of exposure and after 2 weeks in clean water.
      Gamete development and alkali-labile phosphate levels suggest that neither oil
      nor styrene behaved as endocrine disruptors. Neutral red retention time was lower
      in treated groups than in controls. Lysosomal membrane stability was
      significantly reduced in exposed groups and recovered after withdrawal of oil but
      not after removal of styrene. Neither oil nor styrene exposure affected the
      condition index except for the reduction seen in mussels exposed to oil for 1
      month. Biomarker response index discriminated exposed mussels, which showed
      higher values, and returned to control levels after recovery. Results obtained
      from these pilot experiments can help to identify relevant monitoring tools to
      assess the impact of oil and chemicals in marine spill scenarios.

PMID- 24676936
TI  - Successive development of soil ecosystems at abandoned coal-ash landfills.
AB  - The main goal of the present study was to determine the effect of the native
      vegetation on the successive development of the soil ecosystem at abandoned coal
      ash landfills of the Angren coal-fired power plant in Uzbekistan. Two different
      landfills (one not in use for 3 years, termed newer, and the other not in use for
      10 years, termed older) with different degrees of vegetation cover were chosen to
      assess the time and vegetation effects on soil biota and habitat development. The
      soil biotic structure, including soil microorganisms and soil free-living
      nematode communities, was investigated both at open plots and under different
      native plants at the coal-ash landfill area. The observed soil microorganisms
      were found to be the most important component of the observed ecosystems. Total
      abundance, biomass, species, trophic and sexual diversity of soil free-living
      nematodes, along with fungi and organic-matter content, were found to be
      correlated with trace metals. The nematode trophic and species abundance and
      diversity increased from the newer toward the older coal-ash landfills. The sex
      ratio of the nematode communities was found to be dependent on the environmental
      conditions of the study area, with the males being the most sensitive nematode
      group. All applied ecological indices confirmed that open landfill plots distant
      from plants are the most unfavorable areas for soil biota. In that respect, the
      native plants Alhagi maurorum Desv. and Tamarix sp. were found to be important
      environmental components for the natural remediation of a soil ecosystem in the
      coal-ash landfill area. 

PMID- 24676937
TI  - Contribution of reactive oxygen species (ROS) to genotoxicity of nitrobenzene on
      V. faba.
AB  - Nitrobenzene is an important organic intermediate widely used in industry that
      can be hazardous to the environment. In our previous study, nitrobenzene showed
      genotoxic effect on soybean and tobacco plants at concentrations in the culture
      medium higher than 10 mg/L. The genotoxicity of nitrobenzene has been
      hypothesized to be multifactorial and reflective of the generation of free
      radicals; however, the mechanism has not been fully elucidated. The aim of this
      study was to investigate the relationship between the induction of genotoxicity
      and the production of free radicals in young seedlings of V. faba exposed to
      nitrobenzene, nitrobenzene + Vitamin C, and the controls (distilled water or
      Vitamin C). Micronucleus and chromosome aberration assays performed on root and
      leaf tissue of V. faba seedlings exposed to nitrobenzene (25 mg/L) demonstrated
      genotoxic effects which were partly reduced by Vitamin C at 25 mg/L. Increases in
      lipid peroxidase, O2*-, H2O2, superoxide dismutase and catalase activities were
      also observed in these tissues along with an attenuation of their induction by
      Vitamin C. Concomitant occurrence of genotoxicity and the generation of free
      radicals that are attenuated in the presence of Vitamin C, a scavenger of
      cellular free radicals, indicate that reactive oxygen species may contributes to
      genotoxicity of nitrobenzene in V. faba. These results are valuable for further
      understanding the genotoxicity mechanism of nitrobenzene.

PMID- 24676938
TI  - Causes and characteristics of horizontal positional nystagmus.
AB  - Direction changing horizontal positional nystagmus can be observed in a variety
      of central and peripheral vestibular disorders. We tested sixty subjects with
      horizontal positional nystagmus and vertigo on the Epley Omniax((r)) rotator.
      Monocular video recordings were performed with the right or left ear down, in the
      supine and prone positions. Nystagmus slow-phase velocity (SPV) was plotted as a
      function of time. Thirty-one subjects diagnosed with horizontal canalolithiasis
      had paroxysmal horizontal geotropic nystagmus with the affected ear down (onset
      0.8 +/- 1 s, range 0-4.9 s, duration 11.7-47.9 s, peak SPV 79 +/- 67 degrees /s).
      The SPV peaked at 5-20 s and declined to 0 by 60 s; at 40 s from onset, the
      average SPV was 1.8 % of the peak. Nine subjects diagnosed with cupulolithiasis
      had persistent apogeotropic horizontal nystagmus (onset 0.7 +/- 1.4 s, range 0
      4.3 s). Peak SPV was 54.2 +/- 31.8 degrees /s and 26.6 +/- 12.2 degrees /s with
      unaffected and affected ears down, respectively. At 40 s, the average SPV had
      decayed to only 81 % (unaffected ear down) and 65 % (affected ear down) of the
      peak. Twenty subjects were diagnosed with disorders other than benign positional
      vertigo (BPV) [vestibular migraine (VM), Meniere's Disease, vestibular
      schwannoma, unilateral or bilateral peripheral vestibular loss]. Subjects with VM
      (n = 13) had persistent geotropic or apogeotropic horizontal nystagmus. On
      average, at 40 s from nystagmus onset, the SPV was 61 % of the peak. Two patients
      with Meniere's Disease had persistent apogeotropic horizontal nystagmus; the peak
      SPV at 40 s ranged between 28.6 and 49.5 % of the peak. Symptomatic horizontal
      positional nystagmus can be observed in canalolithiasis, cupulolithiasis and
      diverse central and peripheral vestibulopathies; its temporal and intensity
      profile could be helpful in the separation of these entities.

PMID- 24676939
TI  - Action verb comprehension in amyotrophic lateral sclerosis and Parkinson's
      disease.
AB  - Patients with amyotrophic lateral sclerosis (ALS) have a motor disorder and
      cognitive difficulties, including difficulty with action verbs. However, the
      basis for the action verb impairment is unknown. Thirty-six participants with ALS
      and 22 with Parkinson's disease (PD) were assessed on a simple, two-alternative
      forced-choice associativity judgment task, where performance was untimed and did
      not depend on motor functioning. We probed 120 frequency-matched action verbs,
      cognition verbs, concrete nouns and abstract nouns. Performance was related to T1
      MRI imaging of gray matter atrophy. Patients with ALS were significantly impaired
      relative to healthy senior control participants only for action verbs. Patients
      with PD did not differ from controls for all word categories. Regression analyses
      related action verb performance in ALS to motor-associated cortices, but action
      verb judgments in PD were not related to cortical atrophy. These findings are
      consistent with the hypothesis that action verb difficulty in ALS is related in
      part to the degradation of action-related conceptual knowledge represented in
      motor-associated cortex. 

PMID- 24676940
TI  - Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against
      ischemia/reperfusion injury.
AB  - Hyperbaric oxygen (HBO) therapy is an effective therapy for ischemia/reperfusion
      (I/R) injury of the brain, small intestine, testes and liver. However, the
      detailed molecular mechanisms underlying the effect of HBO therapy remain
      undetermined. In the current study, the hypothesis that preconditioning rats with
      HBO protects grafted skin flaps against subsequent I/R injury was investigated.
      In addition, the molecular mechanisms underlying HBO therapy were characterized
      by analyzing the roles of the following important inflammatory factors: High
      mobility group protein 1 (HMGB1) and nuclear factor-kappa B (NF-kappaB). A total
      of 40 rats were randomly divided into the following five groups: (i) Sham surgery
      (SH); (ii) ischemia followed by reperfusion 3 days following surgery (I/R3d);
      (iii) ischemia followed by reperfusion 5 days following surgery (I/R5d); (iv) HBO
      preconditioning (HBO-PC) and ischemia followed by reperfusion 3 days following
      surgery (HBO-PC+3d); and (v) HBO-PC and ischemia followed by reperfusion 5 days
      following surgery (HBO-PC+5d). For the surgical procedure, all pedicled skin
      flaps were first measured and elevated (9x6 cm). The feeding vessels of the skin
      flaps were subsequently clamped for 3 h and released to restore blood flow. The
      rats in the HBO-PC+3d and HBO-PC+5d groups received 1 h HBO for 3 and 5
      consecutive days, respectively, prior to surgery. Following surgery, the rats
      were euthanized, and grafted tissues were collected for western blotting and
      immunohistochemistry. HBO-PC increased blood perfusion in epigastric skin flaps
      and attenuated I/R injury following skin flap graft. Additionally, the elevated
      expression of HMGB1 and NF-kappaB proteins during I/R injury was attenuated by
      HBO-PC treatment. HBO-PC may therefore be applied to reduce I/R injury and
      improve the survival rate of grafted skin flaps. The molecular mechanisms
      underlying the effect of HBO therapy are associated with the attenuation of
      inflammatory responses.

PMID- 24676941
TI  - Synergistic effect of arginine-specific ADP-ribosyltransferase 1 and poly(ADP
      ribose) polymerase-1 on apoptosis induced by cisplatin in CT26 cells.
AB  - Arginine-specific ADP-ribosyltransferase 1 (ART1) and poly(ADP-ribose) polymerase
      1 (PARP-1) are both post-translational modification proteins. Inhibition of PARP1
      induces apoptosis in cancer cells, and ART1 regulates RhoA which promotes
      apoptosis in hepatic cancer cells when inhibited. However, the interaction of
      ART1 and PARP-1 on the effect of apoptosis has not yet been elucidated. In the
      present study, lentiviral vector-mediated ART1-cDNA was transfected into CT26
      cells, and the apoptosis rate was detected by flow cytometric assay and Hoechst
      33342 staining. Relevant factors were detected by reverse transcriptase-PCR and
      western blotting. The results showed that the apoptosis rate in the ART1-cDNA
      CT26 cells treated with PARP-1 inhibitor 5-aminoisoquinoline (5-AIQ) and
      cisplatin increased, when compared with the ART1-cDNA CT26 cells treated with
      cisplatin only or the untreated ART1-cDNA CT26 cells. Further studies have shown
      that PARP-1 is in the downstream of ART1, and plays a role in ART1-mediated CT26
      cell apoptosis through the ROCK1/NF-kappaB/PARP-1 pathway when induced by
      cisplatin. We also found that in cisplatin-treated cells, activated caspase 3
      cleaved PARP-1 and the decreased level of PARP-1 in turn decreased the expression
      of nuclear factor (NF)-kappaB, Cox-2 and increased caspase 3, resulting in the
      enhanced ability of ART1 to regulate CT26 cell apoptosis. Our research provides
      initial sight into the synergistic effect of ART1 and PARP-1 on apoptosis induced
      by cisplatin in murine colon carcinoma CT26 cells.

PMID- 24676942
TI  - Predicting the "First dose in children" of CYP3A-metabolized drugs: Evaluation of
      scaling approaches and insights into the CYP3A7-CYP3A4 switch at young ages.
AB  - First-dose-in-children relies on the prediction of clearance from adults for
      which little information is available on the accuracy of the scaling-approaches
      applied. For CYP3A-metabolized compounds, scaling of clearance is further
      challenged by different isoforms and by the CYP3A7 to CYP3A4 switch at young
      ages. This investigation aimed to evaluate the accuracy of two frequently used
      scaling approaches and to gain insights into the ontogeny of CYP3A. Hence, a
      literature database was compiled containing 203 clearance values from term
      neonates to adults for 18 CYP3A-metabolized compounds. The clearances in adults
      were scaled to children using (i) allometric scaling plus maturation function and
      (ii) a mechanistic approach based on the well-stirred model. Three maturation
      functions were separately evaluated. In children >3 months, all approaches were
      interchangeable heeding the maturation function applied and biases were mostly
      observed in children <3 months. The results from a sensitivity analysis indicate
      that these biases are possibly caused by disregarding the CYP3A7 activity which
      could account for up to 86% of the metabolism in term-neonates. Only the
      mechanistic approach using an overall-CYP3A maturation function led to unbiased
      predictions of clearances across all ages. The current investigation adds to the
      predictions of the first-dose-in-children of compounds (partially) metabolized by
      CYP3A. 

PMID- 24676943
TI  - Fast and robust next-generation sequencing technique using ion torrent personal
      genome machine for the screening of neurofibromatosis type 1 (NF1) gene.
AB  - Neurofibromatosis type 1 (NF1) gene exhibits one of the highest spontaneous
      mutation rates in the human genome. Identification of the NF1 mutation is
      challenging because the NF1 gene is very large and complex, lacking mutational
      "hot spots." There is no clustering of mutations, there are several pseudogenes,
      and a wide spectrum of different types of mutation has been recognized. To date,
      NF1 mutations or deleted regions have been detected with a number of techniques.
      With the appearance of next-generation sequencing (NGS) machines, molecular
      biology is in a new revolutionary phase. Our aim was to work out a method to use
      the high-throughput NGS machine, Ion Torrent PGM, in diagnostic settings for
      neurofibromatosis type 1. In our examination, we could reveal 21 distinct
      variations in NF1 gene in seven patients. This is an absolutely new method for
      exploring the genetic background of neurofibromatosis type 1 exhibiting the
      extremely high throughput of NGS in a diagnostic setting. 

PMID- 24676945
TI  - Chromogenic factor VIII activity assay.
AB  - Factor VIII (FVIII) may be measured by three different methodologies in the
      clinical laboratory: one-stage clotting assay, two-stage clotting assay, and
      chromogenic assay. These assays differ in ease of use, variety of reagents
      available, sensitivity to mild hemophilia A, and interference from lupus
      anticoagulants. This review will outline the methodology for each of the FVIII
      activity assays, with a discussion of assay interferences and variability. In
      some cases, chromogenic FVIII activity assays may be preferable to clot-based
      assays, and these clinical situations will be reviewed as well.

PMID- 24676944
TI  - Inflammation as well as angiogenesis may participate in the pathophysiology of
      brain radiation necrosis.
AB  - Radiation necrosis (RN) after intensive radiation therapy is a serious problem.
      Using human RN specimens, we recently proved that leaky angiogenesis is a major
      cause of brain edema in RN. In the present study, we investigated the same
      specimens to speculate on inflammation's effect on the pathophysiology of RN.
      Surgical specimens of symptomatic RN in the brain were retrospectively reviewed
      by histological and immunohistochemical analyses using hematoxylin and eosin
      (H&E) staining as well as immunohistochemical staining for VEGF, HIF-1alpha,
      CXCL12, CXCR4, GFAP, CD68, hGLUT5, CD45, IL-1alpha, IL-6 TNF-alpha and NF-kB. H&E
      staining demonstrated marked angiogenesis and cell infiltration in the
      perinecrotic area. The most prominent vasculature was identified as thin-walled
      leaky angiogenesis, i.e. telangiectasis surrounded by prominent interstitial
      edema. Two major cell phenotypes infiltrated the perinecrotic area: GFAP-positive
      reactive astrocytes and CD68/hGLUT5-positive cells (mainly microglias).
      Immunohistochemistry revealed that CD68/hGLUT5-positive cells and GFAP-positive
      cells expressed HIF-1alpha and VEGF, respectively. GFAP-positive cells expressed
      chemokine CXCL12, and CD68/hGLUT5-positive cells expressed receptor CXCR4. The
      CD68/hGLUT5-positive cells expressed pro-inflammatory cytokines IL-1alpha, IL-6
      and TNF-alpha in the perinecrotic area. VEGF caused leaky angiogenesis followed
      by perilesional edema in RN. GFAP-positive cells expressing CXCL12 might attract
      CXCR4-expressing CD68/hGLUT5-positive cells into the perinecrotic area. These
      accumulated CD68/hGLUT5-positive cells expressing pro-inflammatory cytokines
      seemed to aggravate the RN edema. Both angiogenesis and inflammation might be
      caused by the regulation of HIF-1alpha, which is well known as a transactivator
      of VEGF and of the CXCL12/CXCR4 chemokine axis.

PMID- 24676946
TI  - [Nursing manpower and solutions in Taiwan].
AB  - The shortage of nursing manpower is a long-term problem worldwide that affects
      Taiwan despite this country's internationally admired achievements in terms of
      its healthcare and national health insurance systems. This article reviews
      discussions related to the nursing shortage issue published by the World Health
      Organization, International Council of Nurses, and Taiwan Ministry of Health and
      Welfare. Next, an overview is given of the nursing workforce profile, causal
      factors behind the nursing shortage, and demand for and supply of nursing
      manpower. Finally, problems, resolutions, and expected outcomes for the nursing
      shortage in Taiwan are analyzed. 

PMID- 24676947
TI  - [Clinical nursing manpower: development and future prospects].
AB  - The significant changes in nursing manpower utilization in Taiwan over the past
      two decades are due in large part to the implementation of the National Health
      Insurance program and the rising need for long-term care. The changes have
      impacted clinical nursing manpower utilization in two important ways. Firstly,
      there has been a substantial increase in overall demand for nursing manpower. In
      particular, the need for clinical nurses has nearly quadrupled during this time
      period. Secondly, the level of difficulty involved in patient care has risen
      dramatically, with factors including increased disease severity and increased
      care quality expectations, among others. These changes, coupled with demands on
      nursing manpower imposed from other sectors, underpin and further exacerbate the
      problem of nursing manpower shortages throughout the healthcare system. To raise
      the quality of the nursing work environment, the Ministry of Health and Welfare
      (MOHW) brought together Taiwan's key professional nursing organizations to
      promote 10 care-reform strategies, establish the nursing-aid manpower system, and
      create the nursing classification system as an approach to effectively attract
      nurses to take positions in the medical system. 

PMID- 24676948
TI  - [Preparing Taiwan nurses for professional practice: a discussion of current
      international trends].
AB  - Taiwan is currently considering revising the minimum educational requirements for
      becoming a licensed registered nurse (RN). This article analyzes this issue from
      an international perspective within the framework of Taiwan's experience.
      Suggestions regarding possible approaches are given. 

PMID- 24676949
TI  - [Human capital vs. manpower: fostering a greater global perspective within the
      nursing profession in Taiwan].
AB  - Nursing today is an occupation greatly influenced and shaped by global standards
      and internationally recognized standard practices and requirements. Therefore,
      cultivating nursing capital and ensuring nursing manpower requires an
      international perspective. Nursing migration is currently a popular approach used
      by many developed countries to address domestic shortfalls in nursing manpower.
      These international medical services have had a great impact on nursing
      education. Being able to communicate in English and to adapt transculturally have
      thus become increasingly important. Ability to communicate well in English is one
      effective way both to minimize nurse-patient misunderstandings and to increase
      the quality of care available to foreign patients. In addition, transcultural
      communication underscores the value of respecting cultural diversity. Fostering
      and enhancing these abilities will enhance and expand the role of Taiwanese
      nurses in the professional global movement and increase their contributions to
      the internal medical community. 

PMID- 24676950
TI  - [The effect of a scenario-based simulation communication course on improving the
      communication skills of nurses].
AB  - BACKGROUND: Limited disease knowledge is frequently the cause of disease-related
      anxiety in myocardial infarction patients. The ability to communicate effectively
      serves multiple purposes in the professional nursing practice. By communicating
      effectively with myocardial infarction patients, nurses may help reduce their
      anxiety by keeping them well informed about their disease and teaching them self
      care strategies. PURPOSE: This research evaluates the communication skills of
      nurses following scenario-based simulation education in the context of
      communication with myocardial infarction patients. METHODS: This study used an
      experimental design and an educational intervention. The target population
      comprised nurses of medicine (clinical qualified level N to N2 for nursing)
      working at a municipal hospital in Taipei City, Taiwan. A total 122 participants
      were enrolled. Stratified block randomization divided participants into an
      experimental group and a control group. The experimental group received clinical
      scenario-based simulation education for communication. The control group received
      traditional class-based education for communication. Both groups received a pre
      test and a Communication Skills Checklist post-test assessment. Results were
      analyzed using SPSS 17.0 for Windows software. RESULTS: A t-test showed
      significant increases in communication skills (p < .001) in the experimental
      group and ANCOVA results identified significant between-group differences (p <
      .001) in communication skills following the education intervention. CONCLUSIONS:
      The results indicate that clinical scenario-based simulation education for
      communication is significantly more effective than traditional class-based
      education in enhancing the ability of nurses to communicate effectively with
      myocardial infarction patients.

PMID- 24676951
TI  - [Between the self and the other: the ethical attitude of providing care to
      others].
AB  - BACKGROUND: The need to face others is an inescapable part of the professional
      responsibilities of nurses. The meaning of "facing the other" is poorly addressed
      in nursing practice. PURPOSE: The purpose of this study was to explore the
      ethical attitudes of nurses related to facing others. METHODS: A qualitative
      approach was used to investigate the living experience of psychiatric nurses in
      the supervision group in terms of improved ability to handle therapeutic groups.
      RESULTS: The process of facing the other was for the other, by the other, and
      then for oneself. The presence of for the other, the sensibility from by the
      other, and the self-examination of for oneself were discussed in detail.
      CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The process of for the other, by the
      other, and then for oneself constructed the significance of learning from the
      patients. The group with that used the free-floating discussion format was found
      to promote the ethical attitude of psychiatric nurses and may be applied in
      clinical practice.

PMID- 24676952
TI  - [The prevalence and signs of Dysphagia among stroke patients in rehabilitation
      units].
AB  - BACKGROUND: Dysphagia, a very common post-stroke symptom, has been linked to
      aspiration pneumonia, malnutrition, and increased length of hospitalization.
      While patients are typically monitored for dysphagia continuously following their
      transfer to a rehabilitation unit, little is known about the results of dysphagia
      reassessments. PURPOSE: This study investigates the prevalence and signs of
      dysphagia among stroke patients in rehabilitation units. METHODS: We analyzed
      patients with stroke admitted to a rehabilitation unit of a medical center in
      southern Taiwan. The procedure included chart review, the repetitive saliva
      swallowing test (RSST), and the modified water swallowing test (MWST). Dysphagia
      was defined as either RSST or MWST abnormal. JMP 9.0 was used to perform
      descriptive statistics, t-test, chi-square test and logistic regression analysis.
      RESULTS: At clinical examination, 53.61% of the study subjects demonstrated
      dysphagia. Chi-square analysis showed that five abnormal signs (could not close
      mouth with water, without mastication, food stuck in the throat, obvious sputum
      sound, and choking after swallowing) are all associated with dysphagia. Multiple
      logistic regression analysis revealed choking is a significant predictor variable
      of dysphagia. CONCLUSIONS: Over half of the rehabilitation unit stroke patients
      in this study had dysphagia. Nurses are the primary care providers for dysphagia
      patients. Therefore, there is a need for ward nurses to have skills to assess,
      recognize, and manage dysphagia and to enhance patient safety.

PMID- 24676953
TI  - [Liability of pediatric nurses for professional negligence in Taiwan: a case
      study].
AB  - BACKGROUND: Liability attribution and professional negligence in pediatric
      nursing are topics that have been neglected in Taiwan. PURPOSE: (1) Identify the
      definitions of related criminal activities in accordance with domestic criminal
      law; (2) Elucidate the facts and the dispute in a current case involving a
      pediatric nurse; (3) Elucidate the principle of 'no punishment without law'; (4)
      Explore the reasons why the pediatric nurse in the current case received a
      verdict of 'not guilty'. METHODS: A literature review and case study approach
      were used to analyze a sentence reconsideration of the first instance No. 1
      (2011) issued by the Taiwan high court, Kaohsiung branch court. RESULTS: The
      conditions for the scrutiny of criminal activity under Taiwan criminal law are
      statement of facts, illegality (justifiable cause), and liability (excuse). In
      this case, the pediatric nurse was accused of failing to prevent an infant from
      suffocation and of not discharging her obligations as a nurse. The pediatric
      nurse rebutted the charge of criminal negligence. The intervening behaviors of
      the pediatric nurse were found to be legal and not culpable. In this case, the
      High Court and Supreme Court made a final criminal judgment based on the
      presumption of innocence, and the pediatric nurse was pronounced innocent of the
      charge. CONCLUSIONS: This article intends to assist pediatric nurses understand
      their liabilities under Taiwan's criminal law. Pediatric nurses should gain a
      better understanding of the nature of liability for professional negligence in
      order to clarify how actions that may be illegal do not necessarily make nurses
      culpable.

PMID- 24676954
TI  - [The effectiveness of continuing care models in patients with chronic diseases: a
      systematic review].
AB  - BACKGROUND: Population aging has caused significant rises in the prevalence of
      chronic diseases and the utilization of healthcare services in Taiwan. The
      current healthcare delivery system is fragmented. Integrating medical services
      may increase the quality of healthcare, enhance patient and patient family
      satisfaction with healthcare services, and better contain healthcare costs.
      PURPOSE: This article introduces two continuing care models: discharge planning
      and case management. Further, the effectiveness and essential components of these
      two models are analyzed using a systematic review method. METHODS: Articles
      included in this systematic review were all original articles on discharge
      planning or case-management interventions published between February 1999 and
      March 2013 in any of 6 electronic databases (Medline, PubMed, Cinahl Plus with
      full Text, ProQuest, Cochrane Library, CEPS and Center for Chinese Studies
      electronic databases). RESULTS: Of the 70 articles retrieved, only 7 were
      randomized controlled trial studies. Three types of continuity-of-care models
      were identified: discharge planning, case management, and a hybrid of these two.
      All three models used logical and systematic processes to conduct assessment,
      planning, implementation, coordination, follow-up, and evaluation activities.
      Both the discharge planning model and the case management model were positively
      associated with improved self-care knowledge, reduced length of stay, decreased
      medical costs, and better quality of life. CONCLUSIONS / IMPLICATIONS FOR
      PRACTICE: This study cross-referenced all reviewed articles in terms of target
      clients, content, intervention schedules, measurements, and outcome indicators.
      Study results may be referenced in future implementations of continuity-care
      models and may provide a reference for future research.

PMID- 24676955
TI  - [The use of music intervention in nursing practice for elderly dementia patients:
      a systematic review].
AB  - BACKGROUND: Although music therapy is now applied widely as an intervention for
      elderly dementia patients, the effectiveness of this therapy is not yet well
      understood. PURPOSE: This study conducts a systematic review of clinical studies
      that address the effectiveness of music therapy in elderly dementia patients.
      METHODS: Databases including MEDLINE, Cochrane Library, ProQuest, EBMR, CINAHL,
      and CEPS were searched for relevant articles published between 2004 and 2013
      using the key words "music" or "music therapy" with "dementia". An initial 272
      original articles were identified. Applying inclusion criteria and excluding
      duplications left 18 articles that used randomized controlled trials to assess
      the effectiveness of music therapy in elderly participants for further analysis
      and synthesis. RESULTS: Music therapy was found effective at improving cognitive
      functions, mental symptoms, and eating problems. However, this therapy was not
      found effective at improving irritable behavior. Type of music and method of
      presentation were the most important factors affecting results. Most studies
      (61.1%) used songs familiar to / favored by the participants; most studies
      delivered 30-minute interventions twice weekly; and most studies used a therapy
      duration of 6 hours. Finally, most studies (77.8%) had music therapy sessions
      performed by either music therapists or trained healthcare providers. CONCLUSIONS
      / IMPLICATIONS FOR PRACTICE: This study supports that music therapy is an
      effective nursing intervention for elderly dementia patients. The authors hope
      that findings are a helpful reference for clinical nurses to develop practical
      music therapy procedures and protocols.

PMID- 24676956
TI  - [Nursing care of endovascular aneurysm repair patients].
AB  - The treatment of aortic disease previously used conventional open surgery to
      replace the aorta with artificial vascular prosthesis after resecting the
      lesioned segment. The recently developed technique of endovascular aneurysm
      repair (EVAR) uses a stent graft to reinforce the diseased aortic wall while
      allowing blood flow continuity and preventing further aortic expansion,
      dissection and aortic rupture. Taiwan's National Health Insurance now covers
      payment for authorized EVAR procedures, making treatments safer for patients who
      are elderly, have congestive heart failure, have multiple comorbidities, or have
      other high-risk factors. EVAR is gradually replacing previous methods to become
      the primary treatment approach for aortic disease. This article discusses the
      development of EVAR, indications, operative procedures, complications,
      postoperative risk factors, and clinical nursing problems. We hope that this
      article provides new information on nursing care for patients undergoing
      endovascular aneurysm repair surgery. 

PMID- 24676957
TI  - [Sarcopenia in the elderly: diagnosis and treatment].
AB  - The proportion of the population aged 65 years and older in Taiwan was 11.15% in
      2012. This is expected to rise to 20% in 2026, at which time, the country would
      become a super-aged society. Sarcopenia, with a worldwide prevalence among people
      65 years of age and older between 9.5% and 50%, has gained increasing attention
      in recent years. It is estimated that two-hundred million people worldwide will
      suffer from sarcopenia within 40 years. The various causes of sarcopenia include
      aging, inappropriate diet, a bedridden or sedentary lifestyle, chronic diseases,
      and hormones. The definition and interpretation of sarcopenia uses a cutoff point
      of 2 standard deviations below the muscle mass in young adults between the ages
      of 18 and 40 years. The quadriceps muscles are most commonly used to assess
      sarcopenia. A bioimpedance analyzer is appropriate for community-based assessment
      work because this instrument is inexpensive, easily operated, and portable.
      Decreased muscle mass in the elderly causes sarcopenia, which leads to movement
      disorders, fall events, fractures, loss of the capacity to live independently,
      frailty, and increased mortality risk. Therefore, developing a comprehensive care
      program for sarcopenia, including resistance training and sufficient protein and
      vitamin D intake, should be a priority task and important research focus for
      nursing professionals. 

PMID- 24676958
TI  - [An experience nursing an uncertain patient with complications after bariatric
      surgery].
AB  - This article describes a nursing care case in which a 33-year-old housewife
      received laparoscopic bariatric surgery and developed complications requiring
      multiple subsequent hospital admissions. Throughout the course of treatment from
      June to September 2010, the patient repeatedly experienced anxiety, helplessness,
      and depression due to recurrent complications that resulted in her loss of
      confidence in the treatment provided by the surgical team. During her fourth
      hospitalization, the Mishel Uncertainty in Illness Theory (MUIT) was applied to
      assess and establish the cause of her feelings of uncertainty toward her illness.
      Through a combination of reinforced emotional support, encouragement, disease
      consultation, individualized care measures, and improved doctor-patient
      communication, the patient's ability to care for herself improved and she
      regained confidence in control of her own physical condition. In addition, the
      active involvement of the patient's family throughout the course of treatment
      enabled her to persevere through the uncertain treatment period and successfully
      return to a normal life. 

PMID- 24676959
TI  - Adhesiotomy with grafting of fat and perifascial areolar tissue for adhesions of
      extraocular muscles after trauma or surgery.
AB  - PURPOSE: To investigate the effect of adhesiotomy with grafting of fat and
      perifascial areolar tissue (A-GFPAT) on eyes with restricted eye movements after
      trauma or surgery. DESIGN: Single-center retrospective interventional,
      consecutive case series. METHODS: Twenty-four eyes of 24 patients that underwent
      A-GFPAT were studied. The changes in the eye movements was evaluated by the Hess
      area ratio (HAR %) and in the binocular single vision (BSV) field scores.
      RESULTS: The HAR % was significantly improved by the A-GFPAT, from 50.9 +/- 32.0%
      (+/-SD) to 66.4 +/- 28.2% at the final visit (Student's t test; P < 0.01). Nine
      of the 24 cases (37.5%) had an improvement of the final HAR % by >10%. The
      preoperative mean BSV field score was 15.4 +/- 13.3, which improved significantly
      to 25.9 +/- 10.5 after the A-GFPAT (P < 0.001). Thirteen cases (56.5%) had an
      improvement of the final BSV score by more than 5 points. There were improvements
      of both HAR % (50%) and BSV score (54.5%) by more than 50% after A-GFPAT in
      patients with old orbital fractures. All patients who had been treated with
      Lactosorb earlier had an improvement of the BSV score, while those treated with
      endoscopic transmaxillary reduction and balloon technique had a lower chance of
      improvement (20%). CONCLUSIONS: Our new technique of A-GFPAT leads to
      improvements of eye movements that had been limited by the adhesion of orbital
      soft tissue and periorbita with less adverse effects. We recommend our surgical
      procedure for eyes with restrictive eye movements or pain caused by adhesions
      following trauma or ocular surgery.

PMID- 24676960
TI  - Retinal venous pressure in the non-affected eye of patients with retinal vein
      occlusions.
AB  - BACKGROUND: To measure the retinal venous pressure (RVP) in both eyes of patients
      with unilateral central retinal vein occlusions and to compare these values to
      controls. METHODS: The study included 31 patients with unilateral central retinal
      vein occlusions (CRVO) and 31 controls who were matched by age, sex, and systemic
      disease. RVP was measured in all patients bilaterally by means of contact lens
      ophthalmodynamometry, and the RVP measurements of the affected and unaffected
      eyes of patients were compared to the RVPs of controls. Ophthalmodynamometry is
      done by applying an increasing pressure on the eye via a contact lens. The
      minimum force required to induce a venous pulsation is called
      ophthalmodynamometric force (ODF). The RVP is defined and calculated as the sum
      of ODF and intraocular pressure (IOP) [RVP = ODF + IOP]. RESULTS: The RVP group
      means +/- SD were as follows: patient's affected eyes (45.0 +/- 11.6 mmHg),
      patient's unaffected eyes (38.0 +/- 11.1 mmHg) ,and (17.7 +/- 6.7 mmHg) in the
      eyes of controls. The values of RVP, even in the patients unaffected eyes, were
      significantly higher than in the eyes of controls (P < 0.001). CONCLUSIONS: In
      patients with CRVO, the RVP is increased in both the affected as well as in the
      unaffected contralateral eye.

PMID- 24676961
TI  - CRAPT: an improved version of APT with compensation for variations in JCH.
AB  - A modified version of the attached proton test (APT) sequence for (13)C spectral
      editing, which we call CRisis-APT (CRAPT), is developed and tested on
      representative organic compounds. CRAPT incorporates (13)C compensation for
      refocusing inefficiency with synchronized inversion sweeps (CRISIS) pulses in
      combination with (1)H broadband inversion pulses to give improved compensation
      for variations in (1)JCH along with improved refocusing efficiency. It is shown
      that CRAPT gives edited (13)C spectra with only small losses in sensitivity
      (between 8% and 15% for strychnine, 1, menthol, 2, cholecalciferol, 3, and
      isotachysterol, 4), compared with basic (13)C spectra obtained on the same
      compounds. CRAPT also gives significantly better signal/noise than DEPTQ for
      nonprotonated carbons. Therefore, we conclude that CRAPT is an improvement over
      APT or DEPTQ or a combination of DEPT135 with a full (13)C spectrum for routine
      (13)C spectral editing of organic compounds.

PMID- 24676962
TI  - Development of a novel transgenic rice with hypocholesterolemic activity via high
      level accumulation of the alpha' subunit of soybean beta-conglycinin.
AB  - Soybean 7S globulin, known as beta-conglycinin, has been shown to regulate human
      plasma cholesterol and triglyceride levels. Furthermore, the alpha' subunit of
      beta-conglycinin has specifically been shown to possess low-density lipoprotein
      (LDL)-cholesterol-lowering activity. Therefore, accumulation of the alpha'
      subunit of beta-conglycinin in rice seeds could lead to the production of new
      functional rice that could promote human health. Herein, we used the low-glutelin
      rice mutant 'Koshihikari' (var. a123) and suppressed its glutelins and prolamins,
      the major seed storage proteins of rice, by RNA interference. The accumulation
      levels of the alpha' subunit in the lines with suppressed glutelin and prolamin
      levels were >20 mg in 1 g of rice seeds, which is considerably higher than those
      in previous studies. Oral administration of the transgenic rice containing the
      alpha' subunit exhibited a hypocholesterolemic activity in rats; the serum total
      cholesterol and LDL cholesterol levels were significantly reduced when compared
      to those of the control rice (var. a123). The cholesterol-lowering action by
      transgenic rice accumulating the alpha' subunit induces a significant increase in
      fecal bile acid excretion and a tendency to increase in fecal cholesterol
      excretion. This is the first report that transgenic rice exhibits a
      hypocholesterolemic activity in rats in vivo by using the beta-conglycinin alpha'
      subunit. 

PMID- 24676963
TI  - Maintenance cognitive stimulation therapy for dementia: single-blind,
      multicentre, pragmatic randomised controlled trial.
AB  - BACKGROUND: There is good evidence for the benefits of short-term cognitive
      stimulation therapy for dementia but little is known about possible long-term
      effects. AIMS: To evaluate the effectiveness of maintenance cognitive stimulation
      therapy (CST) for people with dementia in a single-blind, pragmatic randomised
      controlled trial including a substudy with participants taking
      acetylcholinesterase inhibitors (AChEIs). METHOD: The participants were 236
      people with dementia from 9 care homes and 9 community services. Prior to
      randomisation all participants received the 7-week, 14-session CST programme. The
      intervention group received the weekly maintenance CST group programme for 24
      weeks. The control group received usual care. Primary outcomes were cognition and
      quality of life (clinical trial registration: ISRCTN26286067). RESULTS: For the
      intervention group at the 6-month primary end-point there were significant
      benefits for self-rated quality of life (Quality of Life in Alzheimer's Disease
      (QoL-AD) P = 0.03). At 3 months there were improvements for proxy-rated quality
      of life (QoL-AD P = 0.01, Dementia Quality of Life scale (DEMQOL) P = 0.03) and
      activities of daily living (P = 0.04). The intervention subgroup taking AChEIs
      showed cognitive benefits (on the Mini-Mental State Examination) at 3 (P = 0.03)
      and 6 months (P = 0.03). CONCLUSIONS: Continuing CST improves quality of life;
      and improves cognition for those taking AChEIs.

PMID- 24676964
TI  - Brief psychological intervention after self-harm: randomised controlled trial
      from Pakistan.
AB  - BACKGROUND: Self-harm is a major risk factor for completed suicide. AIMS: To
      determine the efficacy of a brief psychological intervention - culturally adapted
      manual-assisted problem-solving training (C-MAP) - delivered following an episode
      of self-harm compared with treatment as usual (TAU). METHOD: The study was a
      randomised controlled assessor-masked clinical trial (trial registration:
      ClinicalTrials.gov NCT01308151). All patients admitted after an episode of self
      harm during the previous 7 days to the participating medical units of three
      university hospitals in Karachi, Pakistan, were included in the study. A total of
      250 patients were screened and 221 were randomly allocated to C-MAP plus
      treatment as usual (TAU) or to TAU alone. All patients were assessed at baseline,
      at 3 months (end of intervention) and at 6 months after baseline. The primary
      outcome measure was reduction in suicidal ideation at 3 months. The secondary
      outcome measures included hopelessness, depression, coping resources and
      healthcare utilisation. RESULTS: A total of 108 patients were randomised to the C
      MAP group and 113 to the TAU group. Patients in the C-MAP group showed
      statistically significant improvement on the Beck Scale for Suicide Ideation and
      Beck Hopelessness Inventory, which was sustained at 3 months after the completion
      of C-MAP. There was also a significant reduction in symptoms of depression
      compared with patients receiving TAU. CONCLUSIONS: The positive outcomes of this
      brief psychological intervention in patients attempting self-harm are promising
      and suggest that C-MAP may have a role in suicide prevention.

PMID- 24676965
TI  - Dopamine transporter occupancy by methylphenidate and impulsivity in adult ADHD.
AB  - Impulsivity is a multidimensional construct, including impulsive decision-making
      and impulsive action, representing relatively independent neurocircuitries. ADHD
      is treated with methylphenidate, a drug that binds to dopamine transporters. This
      study in 24 adult male patients with ADHD shows that dopamine transporter
      occupancy by methylphenidate in the putamen correlates with improvements in
      cognitive but not in motor impulsivity.

PMID- 24676966
TI  - Use of services and associated costs for young adults with childhood
      hyperactivity/conduct problems: 20-year follow-up.
AB  - BACKGROUND: Although childhood hyperactivity and conduct problems are associated
      with difficulties in adulthood, little is known about later service use or public
      expenditure costs in the UK. AIMS: To describe the use of services and calculate
      recent (past 6 months) and early adulthood (since the age of 18 years) public
      expenditure costs incurred by young adults who had hyperactivity and/or conduct
      problems during childhood. METHOD: A 20-year follow-up of a community sample of 6
      to 7-year-old boys (n = 83) with hyperactivity only, conduct problems only,
      mixed hyperactivity and conduct problems, and no behaviour problems (control).
      Information was obtained about service use; recent (past 6 months), and early
      adulthood (since age 18 years) public expenditure costs were calculated. RESULTS:
      High levels of childhood conduct problems were associated with a two- to
      threefold increase in early adulthood costs, mainly driven by criminal justice
      contacts. Although the mixed problems group had the highest recent costs in terms
      of receipt of benefits and health and social care, they had the lowest criminal
      justice costs. CONCLUSIONS: High levels of early childhood conduct problems are
      particularly associated with increased health, social care and criminal justice
      costs in adulthood.

PMID- 24676967
TI  - Patterns of cortical thinning in idiopathic rapid eye movement sleep behavior
      disorder.
AB  - Idiopathic rapid eye movement sleep behavior disorder is a parasomnia that is a
      risk factor for dementia with Lewy bodies and Parkinson's disease. Brain function
      impairments have been identified in this disorder, mainly in the frontal and
      posterior cortical regions. However, the anatomical support for these
      dysfunctions remains poorly understood. We investigated gray matter thickness,
      gray matter volume, and white matter integrity in patients with idiopathic rapid
      eye movement sleep behavior disorder. Twenty-four patients with polysomnography
      confirmed idiopathic rapid eye movement sleep behavior disorder and 42 healthy
      individuals underwent a 3-tesla structural and diffusion magnetic resonance
      imaging examination using corticometry, voxel-based morphometry, and diffusion
      tensor imaging. In the patients with idiopathic rapid eye movement sleep behavior
      disorder, decreased cortical thickness was observed in the frontal cortex, the
      lingual gyrus, and the fusiform gyrus. Gray matter volume was reduced in the
      superior frontal sulcus only. Patients showed no increased gray matter thickness
      or volume. Diffusion tensor imaging analyses revealed no significant white matter
      differences between groups. Using corticometry in patients with idiopathic rapid
      eye movement sleep behavior disorder, several new cortical regions with gray
      matter alterations were identified, similar to those reported in dementia with
      Lewy bodies and Parkinson's disease. These findings provide some anatomical
      support for previously identified brain function impairments in this disorder.

PMID- 24676968
TI  - Umbilical artery Doppler at 19 to 22 weeks of gestation in the prediction of
      adverse pregnancy outcomes.
AB  - OBJECTIVE: The aim of this study was to determine the clinical utility of Doppler
      assessment of the umbilical artery in the second trimester scan for predicting
      adverse pregnancy outcomes. METHODS: Singleton pregnancies that had undergone
      routine anomaly scan at 19 to 22 weeks of gestation with umbilical and uterine
      artery Doppler measurements. Receiver operating characteristic curves were
      constructed to evaluate the ability of umbilical artery pulsatility index (PI) to
      predict small for gestational age and preeclampsia. RESULTS: The final study
      population comprised 4565 singleton pregnancies. Multiple regression analysis
      showed significant independent contribution of umbilical artery PI in predicting
      SGA <10th and SGA <5th centiles (adjusted odds ratios of 2.51 and 3.51,
      respectively). By using a cutoff of umbilical artery PI >90th centile, the
      likelihood ratio of SGA <5th centile is 2.3 (95% CI: 1.7-3.0). CONCLUSIONS:
      Umbilical artery PI at 19 to 22 weeks of gestation is significantly associated
      with SGA below the tenth and fifth centiles. A multivariate model combining
      umbilical and uterine artery Doppler measurements with additional maternal and
      sonographic characteristics may help predict small for gestational age,
      particularly those below the fifth centile.

PMID- 24676969
TI  - Extracorporeal shockwave increases the effectiveness of systemic antibiotic
      treatment in implant-related chronic osteomyelitis: experimental study in a rat
      model.
AB  - Implant-related chronic osteomyelitis is a serious complication of orthopedic
      surgery requiring implant removal and radical debridement. Extracorporeal
      shockwave (ESW) have demonstrated significant bactericidal effectiveness in vitro
      and effectiveness and safety were evaluated in an animal model of osteomyelitis.
      In this experimental study, we aimed to test our hypothesis that the use of ESW
      together with systemic antibiotic treatment will provide synergy for the
      treatment of implant-related chronic osteomyelitis caused by methicillin
      susceptible Staphylococcus aureus (MSSA). The proximal tibia of 32 rats was
      contaminated with (10) 8 CFU/ml methicillin-sensitive S. aureus (MSSA-ATCC 29213)
      and Kirschner-wires were placed into the medulla of the tibia. After 4 weeks,
      Kirschner-wires were removed and the rats were randomly divided into four groups:
      group I, untreated contaminated control group; group II, receiving only ESW
      therapy; group III, receiving only systemic teicoplanin; group IV, treated with a
      combination of ESW and systemic teicoplanin. ESW was applied twice to the
      infected limbs and all rats were sacrificed at the end of 8th week. The degree of
      tibial osteomyelitis was assessed by quantitative culture analysis. Bacterial
      counts in groups III and IV were significantly reduced relative to the control
      (p=0.002 and 0.001, respectively). The decrease in bacterial counts was more
      pronounced and significant in group IV compared to group III (p=0.024). In group
      II, bacterial counts also decreased, but the differences were in significant
      (p=0.068). Our experimental model suggests that ESW provides significant synergy
      for systemic antibiotic treatment. However, further clinical trials are required
      in order to use this treatment modality safely in patients, even though our study
      demonstrated successful results in the treatment of implant-related chronic
      osteomyelitis in rats.

PMID- 24676971
TI  - Long-term follow-up in a patient with the dermato-neuro syndrome treated with
      high-dose melphalan, thalidomide, and intravenous immunoglobulins for more than 7
      years.

PMID- 24676970
TI  - Changes in light- and nitrogen-use and in aboveground biomass allocation patterns
      along productivity gradients in grasslands.
AB  - Light- and nitrogen-use change was examined along productivity gradients in
      natural grasslands at Laelatu, western Estonia, both at community level and in
      most abundant species. Aboveground biomass (M) ranged from 341 to 503 g m(-2) in
      wet (W) and from 248 to 682 g m(-2) in dry (D) community. Aboveground leaf area
      ratio (aLAR) decreased with rising M in D site, while it increased in W site. In
      a high-aLAR W community (significantly higher compared to D), adjustment of leaf
      morphology through an increase in specific leaf area is responsible for an
      increase in aLAR with rising productivity. In low-aLAR stand, by contrast,
      adjustment of biomass allocation due to decrease in aboveground leaf mass
      fraction is primarily responsible for the tendency of aLAR to decline. In
      conclusion, a decrease in aLAR is not a universal response to increasing M. We
      hypothesise that there exists an optimum of light acquisition efficiency (PhiM)
      along a productivity gradient independent of community type. Aboveground nitrogen
      use efficiency (aNUE) decreased in high-aLAR, W community with increasing M,
      while in low-aLAR, D site, there was no relationship along a gradient, although
      aNUE increased along six plots dominated by graminoids. A trade-off was
      established between leaf nitrogen content per unit leaf area (N A) and aLAR. 

PMID- 24676972
TI  - Construction and characterization of a Vibrio cholerae serogroup O139 vaccine
      candidate by genetic engineering.
AB  - The present study aimed to construct and evaluate the live attenuated Vibrio
      cholerae serogroup O139 vaccine candidate, in which genes encoding protective
      antigens were integrated into the chromosomal DNA. Using the initial strain, O139
      ZJ9693, the toxin-linked cryptic (TLC) and cholera toxin (CTX) genetic elements
      and repeats in the toxin (RTX) gene cluster were deleted from its chromosomal
      DNA, and the cholera toxin genes, ctxB and rstR, were transferred into the
      chromosome to construct the candidate vaccine strain. The expression of ctxB and
      the vaccine virulence were then examined. Polymerase chain reaction (PCR),
      enzymatic digestion and electrophoresis were performed to confirm that TLC, CTX
      and RTX were deleted, and that ctxB and rstR were transferred into the vaccine
      candidate DNA. According to the preliminary evaluation, the ctxB gene exhibited
      cholera toxin subunit B expression, and no enterotoxigenic or cytotoxic effects
      were observed in this strain. In conclusion, a recombinant strain containing
      genes encoding protective antigens that replaced virulence-associated genes was
      successfully constructed in the present study; this candidate strain may have the
      potential to be utilized to further evaluate the immune response.

PMID- 24676973
TI  - Functional inhibition of aquaporin-3 with a gold-based compound induces blockage
      of cell proliferation.
AB  - AQP3 has been correlated with higher transport of glycerol, increment of ATP
      content, and larger proliferation capacity. Recently, we described the gold(III)
      complex Auphen as a very selective and potent inhibitor of AQP3's glycerol
      permeability (Pgly ). Here we evaluated Auphen effect on the proliferation of
      various mammalian cell lines differing in AQP3 expression level: no expression
      (PC12), moderate (NIH/3T3) or high (A431) endogenous expression, cells stably
      expressing AQP3 (PC12-AQP3), and human HEK293T cells transiently transfected (HEK
      AQP3) for AQP3 expression. Proliferation was evaluated in the absence or presence
      of Auphen (5 MUM) by counting number of viable cells and analyzing 5-bromo-2'
      deoxyuridine (BrdU) incorporation. Auphen reduced ~50% the proliferation in A431
      and PC12-AQP3, ~15% in HEK-AQP3 and had no effect in PC12-wt and NIH/3T3. Strong
      arrest in the S-G2/M phases of the cell cycle, supported by analysis of cyclins
      (A, B1, D1, E) levels, was observed in AQP3-expressing cells treated with Auphen.
      Flow-cytometry of propidium iodide incorporation and measurements of
      mitochondrial dehydrogenases activity confirmed absence of cytotoxic effect of
      the drug. Functional studies evidenced ~50% inhibition of A431 Pgly by Auphen,
      showing that the compound's antiproliferative effect correlates with its ability
      to inhibit AQP3 Pgly . Role of Cys-40 on AQP3 permeability blockage by Auphen was
      confirmed by analyzing the mutated protein (AQP3-Ser-40). Accordingly, cells
      transfected with mutated AQP3 gained resistance to the antiproliferative effect
      of Auphen. These results highlight an Auphen inhibitory effect on proliferation
      of cells expressing AQP3 and suggest a targeted therapeutic effect on carcinomas
      with large AQP3 expression.

PMID- 24676974
TI  - [Not Available].

PMID- 24676975
TI  - [Not Available].
AB  - No vaccine that has yet been used has been free from side effects of one sort or
      another but severe side effects due to immunization are very rare. However,
      because our current knowledge of side effects is still partly incomplete, further
      studies should be undertaken to close these gaps of knowledge. The today's
      national and international standards for the manufacturing and quality control of
      vaccines almost exclude immunization risks due to faulty production. To detect
      very rare or delayed side effects, the qualified post-licensure surveillance must
      amend pre-licensure clinical trials on immunogenicity, reactogenicity and
      efficacy of new vaccines. The medical profession, the public and the media should
      be informed in more detail about true and perceived risks of immunization. The
      German Advisory Committee on Immunization (STIKO) will make the necessary
      recommendations. However, just as important as providing information about the
      potential side effects of vaccination is providing information about the much
      greater risk of refusing immunization. 

PMID- 24676976
TI  - [Not Available].
AB  - Vaccination, along with the improvement of social and hygienic living conditions,
      has played a key role in the prevention and control of infectious diseases due to
      its effectiveness, its favourable risk-benefit ratio and strong acceptance on the
      part of society and health policy makers. The further development of vaccination
      programs depends on the continual collection of valid data on the incidence of
      vaccine preventable diseases, immunisation rates, seroprevalence, vaccine related
      complications as well as on the evaluation of existing programs. The Protection
      against Infection Act (IfSG) in effect since January 1, 2001 has closed important
      gaps in the surveillance of vaccine preventable diseases and the implementation
      of vaccination programs in Germany. The data presented here show the decrease in
      the incidence of vaccine preventable diseases following implementation of
      vaccination and increasing vaccine coverage in Germany, underlining the
      effectiveness of vaccines as well as vaccination programs. The acceptance of
      vaccination is influenced by various factors that should be taken into account in
      the organization of vaccination programs. Measures shown to improve vaccination
      rates in international studies include the establishment of vaccine registries,
      reminder and recall systems, education of the public as well as health care
      workers, reimbursement of providers, improvement of access to providers and
      quality control measures. The deficits in Germany described here reveal further
      requirements for the organization of vaccination programs, for the improvement of
      awareness for the importance of vaccine coverage and for the achievement of
      health related goals. 

PMID- 24676977
TI  - [Not Available].

PMID- 24676978
TI  - [Not Available].
AB  - In the European Union three different procedures for licensing medical products
      exist: the national licensing procedure, the centralised licensing procedure as
      well as the mutual recognition facilitation procedure (MRFP). The paper will
      discuss all three procedures with respect to the licensing of vaccines. In
      addition it focuses on the advantages and disadvantages of each procedure and
      discusses the resulting consequences for vaccine application as well as the
      development of vaccination schemes. 

PMID- 24676979
TI  - [Not Available].
AB  - The German Protection against Infection Act (Infektionsschutzgesetz) came into
      action on January 1, 2001. Reporting of complications after vaccination became
      mandatory according to Article 6 No. 3. From January 1, 2001 to October 19, 2001
      a total of 236 reports were registered in a central database and analyzed. Age
      distribution revealed the following pattern: 44.1% of the notifications concerned
      children from 0 to 11 years of age, 6.8% concerned adolescents and 48.7%
      concerned adults. Two deaths and nine lasting health damages were reported. For
      none of the latter adverse events a causal link to vaccination was evident.
      Compared to other sources of reporting (pharmaceutical companies, drug
      commissions) a considerable underreporting has to be considered. Efforts to
      improve the reporting compliance of physicians according to the requirements of
      the Protection against Infection Act are therefore necessary. 

PMID- 24676980
TI  - [Not Available].
AB  - In October 1995, after realising that the strategy of immunising only individuals
      at high risk for hepatitis B infections did not influence the incidence, the
      STIKO (permanent Committee on Vaccination at the Robert Koch-Institute)
      recommended the general immunisation of all infants and children. The number of
      paediatric doses of recombinant vaccine sold between1995 and 2000 shows that HBV
      vaccination is widely accepted by paediatricians. The cases of suspected adverse
      reactions reported from the German spontaneous pharmacovigilance system are
      summarised and discussed. 

PMID- 24676981
TI  - [Not Available].
AB  - The decrease in infectious diseases preventable by immunisation and the absence
      of complications caused by these diseases leads to an increased awareness of
      vaccine-associated adverse events. The analysis of a survey of the vaccine injury
      compensation data from the German Bundeslander shows the decrease in accepted and
      demanded compensation from 1991 to 1999. From 1976 to 1990 1139 of 4569 demands
      were accepted, whereas from 1991 to 1999, acceptance of only 389 of 2543 demands
      was reported. In all, 38% of the accepted compensations refer to the smallpox
      vaccine which is not longer recommended by the STIKO (Permanent Vaccination
      Commission in Germany) since immunisation against smallpox was stopped in the
      1980s. Regional differences show that process elements of the German healthcare
      system as well as political and social reasons express most of the differences in
      rates and prevalence of vaccine associated adverse events. Epidemiological
      questions and questions of causality cannot be answered by the analysis of data
      collected in vaccine injury programs. Valid analysis needs a register of
      individual documented cases of vaccine adverse events. The surveillance of
      adverse events following immunisation will make progress by the analysis of data
      reported according to the Protection against Infection Act (IfSG) and by further
      surveillance systems that should be implemented in the near future. A centralised
      commission with expert opinion concerning causality could increase transparency
      and homogeneity within judgement and documentation of vaccine associated adverse
      events. 

PMID- 24676982
TI  - [Not Available].

PMID- 24676984
TI  - [Not Available].

PMID- 24676983
TI  - [Not Available].

PMID- 24676985
TI  - Comorbidities in lung cancer: prevalence, severity and links with socioeconomic
      status and treatment.
AB  - BACKGROUND: Survival from lung cancer remains poor in Scotland, UK. Although the
      presence of comorbidities is known to influence outcomes, detailed quantification
      of comorbidities is not available in routinely collected audit or cancer registry
      data. The aim of the present study was to assess the prevalence and severity of
      comorbidities in patients with newly diagnosed lung cancer across four centres
      throughout Scotland using validated criteria. METHODS: Between 2005 and 2008, all
      patients with newly diagnosed lung cancer coming through the multidisciplinary
      teams in four Scottish centres were included in the study. Patient demographics,
      WHO/Eastern Cooperative Oncology Group performance status, clinicopathological
      features and primary treatment modality were recorded. RESULTS: Details of 882
      patients were collected prospectively. The majority of patients (87.3%) had at
      least one comorbidity, the most common being weight loss (53%), chronic
      obstructive pulmonary disease (43%), renal impairment (28%) and ischaemic heart
      disease (27%). A composite score was produced that included both number and
      severity of comorbidities. One in seven patients (15.3%) had severe comorbidity
      scores. There were statistically significant variations in comorbidity scores
      between treatment centres and between non-small cell lung carcinoma treatment
      groups. Disease stage was not associated with comorbidity score. CONCLUSIONS:
      There is a high prevalence of multiple, severe comorbidities in Scottish patients
      with lung cancer, and these vary by site and treatment group. Further research is
      needed to determine the relationship between comorbidity scores and survival in
      these patients.

PMID- 24676986
TI  - MRI in rheumatoid arthritis: a useful tool for the clinician?
AB  - Over the last two decades, MRI has emerged as an important clinical tool to
      assist in the diagnosis and management of rheumatic disease. In rheumatoid
      arthritis (RA), MRI has improved our understanding of the pathological basis of
      disease and has provided new information about imaging features that reflect
      joint inflammation and damage. Using MRI, we can now directly observe
      inflammation involving the synovial membrane and tenosynovium, plus joint damage
      including bone erosion and cartilage thinning. Inflammation of bone beneath the
      joint (osteitis) appears as bone oedema which is a feature unique to MRI and
      yields important diagnostic and prognostic information in patients with
      inflammatory arthritis. With the introduction of biologics to rheumatology
      clinical practice, sensitive tools are required to monitor disease activity and
      progression, so that the disease suppressing effect of these new agents can be
      measured. MRI fits the bill for this role as it can inform the clinician about
      the development of bone erosions well before plain radiography, and its ability
      to reveal cartilage damage is emerging. The use of MRI as a marker of outcome in
      clinical trials is being paralleled by its increasing role in the clinic. Both
      extremity and high field MRI have clinical applications in RA and need to be
      considered along with other advanced imaging techniques as useful tools to add to
      the clinician's armamentarium. This review will summarise recent advances in this
      field and will apply current knowledge to specific clinical scenarios relevant to
      modern rheumatology practice. 

PMID- 24676987
TI  - Thirteen intracranial nails: no neurological and neuropsychological disabilities.

PMID- 24676988
TI  - Weekly Teriparatide for Delayed Unions of Atypical Subtrochanteric Femur
      Fractures.
AB  - INTRODUCTION: The occurrence of atypical femur fractures (AFFs) in patients on
      prolonged bisphosphonate treatment has been gaining medical attention, but the
      use of pharmacotherapy for these fractures has not been explored in detail. The
      authors describe a case of AFFs successfully treated with once-weekly
      administration of 56.5 MUg teriparatide (TPTD). CASE PRESENTATION: The patient
      was a 74-year-old female patient who had been taking alendronate for
      approximately 6 years and who suffered with a fall while walking. X-rays revealed
      a subtrochanteric right femur fracture. The contralateral femur showed cortical
      thickening and a transverse radiolucent fracture line. Based on these specific
      features, the patient was diagnosed with AFF. The patient underwent
      osteosynthesis with intramedullary nailing for the right fracture. Alendronate
      treatment was discontinued. Low-intensity pulsed ultrasonography therapy did not
      affect the healing of the fracture with delayed union, even after 3 months of
      application. Prophylactic osteosynthesis was performed for the subtrochanteric
      left femur. Bone tissue collected from the left fracture site during surgery
      showed severe suppression of bone turnover. Union of bilateral femurs was
      achieved after 3 months of a once-weekly administration of TPTD. CONCLUSION: Once
      weekly TPTD treatment is shown to be beneficial for improving the healing of AFFs
      showing delayed union.

PMID- 24676989
TI  - One-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone
      in Short Children Born Small for Gestational Age.
AB  - BACKGROUND: This prospective, open-label, non-comparative, multicentre, long-term
      phase IV study is examining the efficacy and safety of somatropin [recombinant
      human growth hormone (rhGH)] in short children born small for gestational age
      (SGA) and its impact on the incidence of diabetes. This report is the first
      interim analysis of patients who have completed 1 year of treatment. METHODS: A
      total of 278 pre-pubertal patients were enrolled. Key eligibility criteria
      included height standard deviation score (HSDS) <-2.5; parental adjusted SDS <-1;
      birth weight and/or length <-2 SD and failure to show catch-up growth by >=4
      years of age. Patients were treated with rhGH 0.035 mg/kg/day. The primary
      objective was to evaluate the long-term effect of rhGH on carbohydrate metabolism
      [including fasting glucose, stimulated glucose (2-h oral glucose tolerance test,
      OGTT) and glycated haemoglobin (HbA1c)]. Secondary objectives included evaluation
      of height parameters [body height, HSDS, height velocity (HV), HVSDS]; insulin
      like growth factor 1 (IGF-I) and insulin-like growth factor-binding protein 3
      (IGFBP-3) serum levels during treatment; and incidence and severity of adverse
      events (AEs). RESULTS: None of the children developed diabetes mellitus within
      the first year of treatment. Mean levels of fasting glucose, HbA1c and 2-h OGTT
      values remained stable during the study period. Treatment with rhGH was
      effective, as documented by all height parameters. Mean HSDS improved from -3.39
      at baseline to -2.57 at Year 1. Mean HV increased markedly from 4.25 cm/year at
      baseline to 8.99 cm/year during the first year. Similarly, mean peak-centred
      HVSDS increased from -2.13 at baseline to +4.16 at Year 1. Mean IGF-I SDS and
      IGFBP-3 SDS also increased within the first year (by +1.80 and +0.41,
      respectively). 13 patients (4.7%) did not respond adequately to treatment (HVSDS
      <1); they were withdrawn from the study. In total, 192 children (69.3%)
      experienced treatment-emergent AEs; most (98.7%) were mild-to-moderate, and the
      majority (96.5%) were unrelated to study treatment. CONCLUSION: This interim
      analysis shows that short children born SGA can be effectively and safely treated
      with rhGH and that rhGH treatment has no major impact on carbohydrate metabolism
      after the first year of treatment.

PMID- 24676990
TI  - Oxidative stress and BDNF as possible markers for the severity of crack cocaine
      use in early withdrawal.
AB  - RATIONALE: An important goal of addiction research is to discover neurobiological
      markers that could predict the severity of addiction and help to determine
      appropriate treatment. Brain-derived neurotrophic factor (BDNF) and
      thiobarbituric acid reactive substances (TBARS) are being related to cerebral
      plasticity and impairment caused by substance abuse. OBJECTIVES: This study aims
      to evaluate alteration of TBARS and BDNF levels among crack cocaine users during
      early drug withdrawal and its relationship to severity of drug use. METHODS:
      Forty-nine adults crack cocaine users were recruited at a public psychiatric
      hospital with a specialized addiction treatment unit. Blood sample was collected
      at intake and discharge for the analysis of TBARS and BDNF measures. Information
      about drug use was assessed by the Addiction Severity Index 6th Version (ASI-6).
      Detailed information about crack cocaine use was obtained through the "Profile of
      the crack cocaine user." Severity of crack use was estimated using information
      from age of first crack use, years of crack use, and crack rocks used in the
      previous 30 days. RESULTS: There is a positive correlation between TBARS levels
      and severity of crack cocaine use (R = 0.304, p = 0.04) and a negative
      correlation between BDNF and severity of crack cocaine use (R = -0.359, p = 0.01)
      at discharge. Also, we found an inverse correlation between TBARS and BDNF levels
      (R = -0.294, p = 0.004) at discharge. CONCLUSIONS: Our findings suggest that BDNF
      and TBARS could be possible markers for the severity of drug use. Further studies
      may show how those markers could be related to staging, prognosis, and treatment
      in crack cocaine dependence.

PMID- 24676991
TI  - Mineral contents and proximate composition of Pistacia vera kernels.
AB  - The mineral contents of Pistacia vera kernels were determined by inductively
      coupled plasma-atomic emission spectroscopy (ICP-AES). The minimum and maximum
      values of K, P, Ca, Mg, and S elements ranged from 6,333 to 8,064 mg/kg, 3,630 to
      5,228 mg/kg, 1,614 to 3,226 mg/kg, 1,716 to 2,402 mg/kg, and 1,417 to 1,825
      mg/kg, respectively. In addition, the mean values of Fe, Zn, Cu, Mn, B, Mo, Cr
      and Ni elements were determined as 42.48, 20.52, 12.81, 7.48, 11.31, 0.106, 0.511
      and 1.67 mg/kg, respectively. Ash levels of kernels were found between 2.28 %
      (Urfa) and 2.79 % (Halebi). In addition, crude oil and protein contents were
      determined between 48.8 % (Halebi) to 55.3 % (Siirt) and 23.33 % (Uzun) to 27.16
      % (Halebi), respectively. 

PMID- 24676992
TI  - Does irrigation with reclaimed water significantly pollute shallow aquifer with
      nitrate and salinity? An assay in a perurban area in North Tunisia.
AB  - In Tunisia, reclaimed water is increasingly used for irrigation in order to
      mitigate water shortage. However, few studies have addressed the effect of such
      practice on the environment. Thus, we attempted in this paper to assess the
      impact of irrigation with reclaimed water on the nitrate content and salinity in
      the Nabeul shallow aquifer on the basis of satellite images and data from 53
      sampled wells. Ordinary and indicator kriging were used to map the spatial
      variability of these groundwater chemical parameters and to locate the areas
      where water is suitable for drinking and irrigation. The results of this study
      have shown that reclaimed water is not an influential factor on groundwater
      contamination by nitrate and salinity. Cropping density is the main factor
      contributing to nitrate groundwater pollution, whereas salinity pollution is
      affected by a conjunction of factors such as seawater interaction and lithology.
      The predictive maps show that nitrate content in the groundwater ranges from 9.2
      to 206 mg/L while the electric conductivity ranges from 2.2 to 8.5 dS/m. The high
      nitrate concentration areas underlie sites with high annual crop density, whereas
      salinity decreases gradually moving away from the coastline. The probability maps
      reveal that almost the entire study area is unsuitable for drinking with regard
      to nitrate and salinity levels. Appropriate measures, such as the elaboration of
      codes of good agricultural practices and action programs, should be undertaken in
      order to prevent and/or remediate the contamination of the Nabeul shallow
      aquifer. 

PMID- 24676993
TI  - Seasonal perspective of dietary arsenic consumption and urine arsenic in an
      endemic population.
AB  - Exposure to arsenic in arsenic endemic areas is most remarkable environmental
      health challenges. Although effects of arsenic contamination are well
      established, reports are unavailable on probable seasonal variation due to
      changes of food habit depending on winter and summer seasons, especially for
      endemic regions of Nadia district, West Bengal. Complete 24-h diets, drinking
      cooking water, first morning voided urine samples, and diet history were analyzed
      on 25 volunteers in arsenic endemic Chakdah block of Nadia district, once in
      summer followed by once in winter from the same participants. Results depicted no
      seasonal variation of body weight and body mass index. Arsenic concentration of
      source drinking and cooking water decreased (p = 0.04) from 26 MUg L(-1) in
      summer to 6 MUg L(-1) in winter season. We recorded a seasonal decrease of water
      intake in male (3.8 and 2.5 L day (-1)) and female (2.6 and 1.2 L day(-1))
      participants from summer to winter. Arsenic intake through drinking water
      decreased (p = 0.04) in winter (29 MUg day(-1)) than in summer (100 MUg day(-1)),
      and urinary arsenic concentration decreased (p = 0.018) in winter (41 MUg L(-1))
      than in summer (69 MUg L(-1)). Dietary arsenic intake remained unchanged (p =
      0.24) over the seasons. Hence, we can infer that human health risk assessment
      from arsenic needs an insight over temporal scale. 

PMID- 24676994
TI  - Thiamine-responsive megaloblastic anemia in an Iraqi girl.

PMID- 24676995
TI  - L-securinine induces apoptosis in the human promyelocytic leukemia cell line HL
      60 and influences the expression of genes involved in the PI3K/AKT/mTOR signaling
      pathway.
AB  - The Securinega alkaloids are a class of natural products isolated from plants of
      the Euphorbiaceae family. L-securinine induces apoptosis in the human
      promyelocytic leukemia cell line HL-60 indicating its potential as an efficient
      natural antitumor drug with low toxicity. The aim of the present study was to
      investigate the apoptotic effects of L-securinine on HL-60 cells and to explore
      its potential underlying molecular mechanism(s) as an antitumor agent. HL-60
      cells were cultured with L-securinine. The proliferation and changes in cell
      morphology were evaluated by cell counting Kit-8 (CCK-8) assay and electron
      microscopy, respectively. Induction of apoptosis and cell cycle progression were
      investigated by flow cytometry. The PI3K/AKT/mTOR pathway gene expression was
      measured by quantitative PCR (qPCR). L-securinine decreased the viability of HL
      60 cells in a dose- and time-dependent manner, with IC50 values at 24, 48 and 72
      h post-treatment of 47.88, 23.85 and 18.87 umol/l, respectively. Numerous
      apoptotic bodies were observed in the HL-60 cells treated with 25 umol/l L
      securinine for 48 h. L-securinine at 12.5, 25 and 50 umol/l increased the rate of
      apoptosis in HL-60 cells, and G1/S phase progression was retarded. Furthermore, L
      securinine induced downregulation of PI3K, AKT and mTOR gene expression and
      upregulation of PTEN gene expression in a dose-dependent manner. In conclusion, L
      securinine induces apoptosis and inhibition of cell cycle progression in HL-60
      cells by modulation of the PI3K/AKT/mTOR pathway gene expression. These
      observations indicate the potential of L-securinine as an antitumor agent.

PMID- 24676996
TI  - Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) polymorphisms are
      associated with NSCLC risk in a Chinese population.
AB  - Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) encodes a plasma
      membrane protein of divalent cation channels and is expressed in keratinocytes.
      This study aimed to investigate CHRNA9 single-nucleotide polymorphisms (SNPs) for
      association with non-small cell lung cancer (NSCLC), especially squamous cell
      carcinoma (SCC) risk, in a Chinese population. This case-control study included
      500 NSCLC patients and 500 age-matched healthy controls. CHRNA9 rs56159866,
      rs6819385, rs55998310, and rs182073550 SNPs were genotyped and associated for
      NSCLC risk by computing the odds ratios (ORs) and 95 % confidence intervals (CIs)
      from multivariate unconditional logistic regression analyses with adjustment for
      age. The frequencies of the CHRNA9 rs6819385 G allele were 16.1, 15.2, and 20.8%
      in male NSCLC patients, male SCC patients, and male controls, respectively. The
      CHRNA9 rs6819385 A allele was associated with an increased risk of developing
      NSCLC (P = 0.04, OR = 1.37; 95% CI 1.02-1.83) and SCC (P = 0.04, OR = 1.47; 95%
      CI 1.01-2.13). The CHRNA9 rs6819385 A/A homozygote was associated with an
      increased risk of NSCLC and SCC in all patients (OR = 1.38; 95% CI 1.06-1.79; P =
      0.02, and OR = 1.61; 95% CI 1.09-2.38; P = 0.02, respectively) and in male
      patients (OR = 1.57; 95% CI 1.11-2.21; P = 0.01, and OR = 1.70; 95% CI 1.11-2.61;
      P = 0.01, respectively), indicating that the CHRNA9 rs6819385 A/A homozygote had
      a 1.61-fold and 1.70-fold increased risk of developing lung SCC in all patients
      (95% CI 1.09-2.38, P = 0.02) and in males (95% CI 1.11-2.61, P = 0.01),
      respectively. The CHRNA9 rs6819385 SNP was significantly associated with an
      increased risk of NSCLC, especially for SCC in male patients in this Chinese
      population.

PMID- 24676998
TI  - A single-dose, open-label, parallel, randomized, dose-proportionality study of
      paliperidone after intramuscular injections of paliperidone palmitate in the
      deltoid or gluteal muscle in patients with schizophrenia.
AB  - Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotic,
      developed for monthly intramuscular (i.m.) administration into deltoid/gluteal
      muscle, approved for the treatment of schizophrenia in many countries. To assess
      the options for i.m. injection sites, dose-proportionality of PP was investigated
      after injection of a single dose (25-150 mg eq.) of PP in either gluteal (n =
      106) or deltoid (n = 95) muscle of schizophrenic patients. Overall, mean
      (geometric) area under plasma concentration-time curve from time zero to infinity
      (AUCinfinity ) of paliperidone increased proportionally with increasing PP doses,
      regardless of injection site. Mean maximum plasma concentration (Cmax ) was
      slightly less than dose-proportional for both injection sites at PP doses >50 mg
      eq. Mean Cmax was higher after injection in the deltoid compared with the gluteal
      muscle, except for the 100 mg eq. dose, while AUCinfinity for both injection
      sites was comparable at all doses. Median time to reach Cmax (tmax ) ranged from
      13-14 days after deltoid and 13-17 days after gluteal injection across all doses.
      Single PP injections in deltoid and gluteal muscles in the dose range of 25-150
      mg eq. were generally tolerable both locally and systemically. 

PMID- 24676997
TI  - Down-regulation of Dicer expression in cervical cancer tissues.
AB  - Dicer is a component of the MicroRNA-producing machinery. The altered expression
      of Dicer may play a role in oncogenesis. The purpose of this study was to
      evaluate the expression of Dicer in cervical cancer tissues and its significance.
      Cancer tissues, para-cancer tissues and corresponding normal tissues were
      obtained from 31 cervical cancer patients undergoing surgery. Expression levels
      of Dicer mRNA were evaluated in these tissues using the real-time reverse
      transcription PCR. The association of the Dicer expression levels with clinical
      characteristics was also examined. The expression levels of Dicer mRNA were
      decreased in 66.7% (18/27) and 76.9% (20/26) of cervical cancer and para-cancer
      specimens, respectively, compared with corresponding normal tissues. The lower
      expression levels of Dicer in cancer tissues were associated with advanced tumor
      stages (p = 0.03) and with metastasis (p = 0.01). The down-regulation of Dicer
      expression in cancer and para-cancer tissues was observed. The lower expression
      of Dicer in cancer tissues demonstrated to be associated with tumor stages and
      metastasis. Future studies with a greater number of tissues to more conclusively
      determine the extent of low-level expression of Dicer in cervical cancer are
      warranted.

PMID- 24676999
TI  - A novel DCTN1 mutation with late-onset parkinsonism and frontotemporal atrophy.
AB  - BACKGROUND: Depression, parkinsonism, and hypoventilation (Perry syndrome) or
      familial motor neuron disease have been linked to mutations in dynactin
      P150(Glued) (DCTN1). METHODS: We employed genealogic, clinical, neurologic, and
      MRI investigations, as well as analysis of genes implicated in parkinsonism.
      Cellular transfection, immunocytochemistry, and immunoprecipitation analysis of
      wild-type (WT) and mutant DCTN1 were also performed. RESULTS: A novel
      heterozygous mutation, DCTN1 c.156T>G, encoding p.Phe52Leu, segregates with
      parkinsonism in a Japanese family. The substitution was not observed in affected
      probands with familial parkinsonism or control subjects and is evolutionarily
      conserved. In contrast to Perry syndrome, affected carriers have late-onset
      disease and slower progression, with frontotemporal atrophy revealed by MRI. In
      vitro studies suggest the mutant protein has impaired microtubule binding,
      compared to WT dynactin p150(Glued) . CONCLUSIONS: DCTN1 mutations may contribute
      to disparate neurodegenerative diagnoses, including familial motor neuron
      disease, parkinsonism, and frontotemporal atrophy, and further studies of
      dynactin-mediated cargo transport may prove insightful.

PMID- 24677000
TI  - Normal anatomy of urethral sphincter complex in young Chinese males on MRI.
AB  - PURPOSE: In this research, the normal anatomy of urethral sphincter complex in
      young Chinese males has been studied. METHODS: The sagittal, coronal, and axial
      T2-weighted non-fat suppressed fast spin-echo images of pelvic cavities of 86
      Chinese young males were studied. RESULT: Urethral sphincter complex is a
      cylindrical structure surrounding the urethra and extending vertically from
      bladder neck to perineal membrane. Urethral striated sphincter covers the
      anteriolateral urethra like a hat from bladder neck to verumontanum, while it
      surrounds the urethra in a ring shape from verumontanum to perineal membrane and
      backwards ends in central tendon of the perineum. From bladder neck to perineal
      membrane, the thickness of urethral smooth sphincter decreases gradually, and it
      extends forward to surround urethra with urethral striated sphincter as a ring.
      The length of urethral striated sphincter is 12.26-20.94 mm (mean 16.59 mm) at
      membranous urethra: 27.88-30.69 mm (mean 28.99 mm) from verumontanum to perineal
      membrane. The thickness of striated sphincter at membranous urethra is 4.29-6.86
      mm (mean 5.56 mm) for the muscle of the anterior wall and 2.18-2.34 mm (mean 2.26
      mm) for the muscle of the posterior wall. CONCLUSIONS: In this paper, we
      summarized the normal anatomy of urethral sphincter complex in young Chinese
      males with no urinary control problems.

PMID- 24677001
TI  - Expanding the use of expanded criteria donors in kidney transplantation.
AB  - PURPOSE: Although the use of kidney allografts from expanded criteria donors
      (ECD) has increased in recent years, the reported discard rates are also growing.
      The influence of ECD characteristics on transplant outcomes is still
      underevaluated. METHODS: This retrospective study investigated the influence of
      preimplantation biopsy findings and delayed graft function (DGF) on patient and
      graft survivals and renal function at 36 months in a cohort of 372 ECD kidney
      transplant recipients. RESULTS: Patient and graft survivals were 91.6 and 68.9 %.
      The incidence of biopsy-proven acute rejection was 31 %. There were no
      differences in patient (88.6 vs. 91.1 vs. 94.7 vs. 78.6 %, p = 0.10) or graft
      (78.1 vs. 72.2 vs. 60.5 vs. 62.6 %, p = 0.14) survivals and renal function (41.7
      +/- 25.6 vs. 39.9 +/- 29.9 vs. 38.1 +/- 30.6 vs. 37.4 +/- 29.2 mL/min, p = 0.79)
      comparing ECD kidneys with mild, moderate, and severe histological changes or
      with no preimplantation biopsy, respectively. However, severe scored transplants
      had the worst death-censored graft survival (OR 3.1, 95 % CI 1.4-6.9, p = 0.007).
      No significant differences in patient (86.2 vs. 83.4 %, p = 0.17) or graft (73.7
      vs. 65.9 %, p = 0.06) survivals and renal function (38.9 +/- 28.6 vs. 39.9 +/-
      28.4 mL/min, p = 0.72) were observed comparing patients with or without DGF.
      Multivariable analysis found diabetes history as the only independent risk factor
      for graft loss (OR 2.1, 95 % CI 1.3-3.3, p = 0.003) or patient death (OR 3.1, 95
      % CI 1.5-5.8, p < 0.001). CONCLUSIONS: Within the limitations of sample size and
      short follow-up time, in this cohort of ECD kidney transplant recipients the
      severity of histological changes observed in preimplantation biopsies was
      independently associated with graft loss.

PMID- 24677002
TI  - Do blood groups have effect on prognosis of patients undergoing radical
      cystectomy?
AB  - PURPOSE: The purpose of the study was to investigate the effect of ABO blood
      groups and Rhesus (Rh) factor on prognosis of patients undergoing radical
      cystectomy. MATERIALS AND METHODS: In this study, total number of 290 patients
      who underwent radical cystectomy between January 1990 and September 2012 were
      evaluated retrospectively. Patients were grouped as O and non-O according to ABO
      antigens; also positive and negative according to Rh factor. Parameters such as
      age, sex, stage, lymph node involvement and positive surgical margins were
      investigated. Disease-free and overall survival rates have been compared.
      Multivariate analysis were performed to determine independent prognostic factors.
      RESULTS: A total of 260 (89.7 %) male and 30 (10.3 %) female patients
      participated in the study. Mean follow-up was 37.7 +/- 18.9 months. A total of
      180 patients were non-O (62.1 %),while the 110 patients had the blood group O
      (37.9 %). The number of Rh positive and negative patients were 247 (85.2 %) and
      43 (14.8 %), respectively. According to the univariate and multivariate analyses,
      ABO blood groups and Rh factor did not exhibit any significant impact on overall
      and disease-specific survival. CONCLUSION: ABO blood group and Rh factor were not
      associated with the prognosis of bladder cancer patients who underwent radical
      cystectomy. However, prospective studies are needed in larger patient series for
      further evaluations.

PMID- 24677003
TI  - Coffee consumption and urologic cancer risk: a meta-analysis of cohort studies.
AB  - OBJECTIVES: Controversial results were reported among several epidemiologic
      studies on the relationship between coffee consumption and urologic cancer risk.
      We, therefore, conducted this meta-analysis to clarify these associations.
      METHODS: Electronic databases including Pubmed, Embase and Cochrane library were
      searched between January 1966 and August 2013 for eligible studies. Pooled
      relative risk (RR) and its 95 % confidence interval (CI) were calculated. All P
      values are two tailed. RESULTS: Thirteen cohorts were eligible for inclusion. As
      to prostate cancer (PCa), significant reverse association was found among highest
      versus none/lowest analysis with acceptable heterogeneity (RR 0.86, 95 % CI 0.79
      0.95; I(2) 25 %, P value for heterogeneity: 0.221). A pooled RR which assessed
      advanced PCa was 0.73 (with 95 % CI 0.50-1.07), and a slight stronger reverse
      association was found in fatal PCa. However, a slight insignificant reverse
      association, basing on 8 studies with 9 outcomes, was found in dose-response
      analysis (RR 0.98, 95 % CI 0.93-1.03). For kidney and bladder cancer,
      insignificant associations were found in both highest versus none/lowest analyses
      and dose-response analyses. CONCLUSIONS: Our findings suggest that coffee
      consumption may reduce the risk of PCa. No associations were found with both
      bladder and kidney cancer. Further well-designed large-scaled cohort studies are
      warranted to provide more definitive conclusions.

PMID- 24677004
TI  - Evaluation of contrast sensitivity measurements after retrobulbar optic neuritis
      in Multiple Sclerosis.
AB  - BACKGROUND: The evaluation of contrast sensitivity is an important additional
      examination that allows the physician to achieve the full picture of a patient's
      quality of vision. In low-contrast conditions, more discrete visual dysfunctions
      may be revealed, which could be overlooked in high-contrast tests. METHODS: The
      examined group consisted of 33 eyes of 27 patients with multiple sclerosis. The
      study included patients with full or almost full visual acuity, without visual
      field defects or any other ophthalmic condition, and who had never undergone any
      ocular surgery or trauma. The reference group consisted of 49 eyes of 37
      patients. This group included healthy subjects with full visual acuity. Contrast
      sensitivity was examined with a Functional Vision AnalyzerTM device in photopic
      conditions (with and without glare) and in mesopic conditions (with and without
      glare). RESULTS: In patients with multiple sclerosis who had experienced optic
      neuritis, contrast sensitivity was found to be significantly reduced in all
      spatial frequencies in both mesopic and photopic conditions (with and without
      glare). CONCLUSIONS: Contrast sensitivity in patients with multiple sclerosis who
      have also had optic neuritis is significantly reduced. This may explain patients'
      complaints regarding their quality of vision, despite good visual acuity.
      Contrastometry is a useful basis for further examination, providing additional
      information regarding a patient's quality of vision.

PMID- 24677005
TI  - [Applying root cause analysis to promote the medication safety of continuous drug
      infusions for infants].
AB  - BACKGROUND & PROBLEMS: An adverse medication event involving a continuous drug
      infusion dosage error was reported in the infant intensive care unit of our
      hospital in 2010. The causes of this adverse medication event were elicited in
      the healthcare network using root cause analysis. These causes included
      incomplete procedures and incorrect prescription, an incomplete procedure of
      medication in continuous drug infusion, complex procedures in confirming
      prescription, the transcription of doctor's orders and prescription (i.e.,
      kardex), and deficient knowledge of medication procedures exhibited by clinical
      nurses. PURPOSES: The main purpose of this project was to achieve a 100%
      completion rate for nurse administrations of continuous intravenous medication
      and zero adverse medication events. RESOLUTIONS: Strategies included simplifying
      the prescription verification process, establishing regulations for drug
      prescription, standardizing the steps required for continuous intravenous
      medication administration, developing the dosage criteria for continuous
      intravenous medication, and developing a double-check mechanism for high-risk
      medications. In addition, relevant nurse's continuous educational programs were
      provided to help nurses effectively implement drug administration. RESULTS: The
      completion rate for administering the medication steps has increased to 99% and
      the compliance rate for pediatricians' orders regarding medication prescription
      has increased to 96%. Furthermore, no additional adverse medication events were
      observed after the intervention. CONCLUSIONS: This project established a systemic
      drug administration mechanism to promote communication and cooperation among
      healthcare teams and further enhanced medication safety and quality for infants.

PMID- 24677006
TI  - [Project to improve the follow-up rate for patients with abnormal oral mucosal
      screenings at a regional hospital].
AB  - BACKGROUND & PROBLEMS: The Bureau of Health Promotion provides oral mucosal
      screening services for those at high-risk of oral cancer in order to detect and
      treat early-stage oral cancer. However, the low rate of follow up for abnormal
      cases been associated with a rising mortality rate. PURPOSE: This project seeks
      to improve the follow-up rate of patients with abnormal oral mucosal diagnoses at
      our hospital. RESOLUTIONS: We analyzed the current data and found that reasons
      for poor follow up included: patients' lack of knowledge, inconvenience in
      accessing the hospital, unwillingness to pay additional fees, and inadequate
      health education from healthcare providers. Therefore, we proposed several action
      measures that were developed between June and October 2012. These measures
      included: designating healthcare staff for oral mucosal screening, improving
      procedures in oral mucosal screening, tracking and referral of abnormal cases,
      encouraging medical staff to provide more health education in clinical sessions,
      and increasing distribution of health-education materials. RESULTS: After
      implementation, the follow-up rate for abnormal oral mucosal cases in our
      hospital increased from 64.2% to 95.3%. CONCLUSIONS: This project significantly
      improved the follow-up rate for abnormal oral mucosal cases as part of our
      overall goal of the early detection and treatment of oral cancer.

PMID- 24677007
TI  - [Improving the provision of nesting and positioning for premature infants by
      nurses in neonatal intensive care units].
AB  - BACKGROUND & PROBLEMS: Nesting and positioning is a common nursing skill used in
      the developmental care of premature infants. This skill maintains premature
      infants in a comfortable position, facilitates the monitoring of stable vital
      signs, and enables spontaneous motor activity for normal neuromuscular and
      skeletal joint function. PURPOSE: This project was designed to improve nursing
      staff cognition and skills regarding nesting and positioning for premature
      infants in the NICU. RESOLUTIONS: Strategies used in this project were: develop
      an infant position assessment tool; record a demonstration video about nesting
      and positioning skills to provide learning efficacy among the nursing staff; and
      modify an education program for new nurses. RESULTS: After implementation, nurse
      cognition regarding premature infant nesting and positioning increased from 58.3%
      to 92.3%. The rate of correct technique use similarly rose from 63.3% to 91.4%.
      CONCLUSIONS: This is a valid intervention for improving the correctness of
      nesting and positioning in nursing care. This project standardized education in
      terms of nesting and positioning practice goals and enhanced quality care for
      premature infants.

PMID- 24677008
TI  - [Applying healthcare failure mode and effect analysis to improve the surgical
      specimen transportation process and rejection rate].
AB  - BACKGROUND & PROBLEMS: Because surgical pathology specimens are crucial to the
      diagnosis and treatment of disease, it is critical that they be collected and
      transported safely and securely. Due to recent near-miss events in our
      department, we used the healthcare failure model and effect analysis to identify
      14 potential perils in the specimen collection and transportation process.
      Improvement and prevention strategies were developed accordingly to improve
      quality of care. PURPOSE: Using health care failure mode and effect analysis
      (HFMEA) may improve the surgical specimen transportation process and reduce the
      rate of surgical specimen rejection. RESOLUTIONS: Rectify standard operating
      procedures for surgical pathology specimen collection and transportation. Create
      educational videos and posters. Rectify methods of specimen verification.
      Organize and create an online and instantaneous management system for specimen
      tracking and specimen rejection. RESULTS: Implementation of the new surgical
      specimen transportation process effectively eliminated the 14 identified
      potential perils. In addition, the specimen rejection fell from 0.86% to 0.03%.
      CONCLUSIONS: This project was applied to improve the specimen transportation
      process, enhance interdisciplinary cooperation, and improve the patient-centered
      healthcare system. The creation and implementation of an online information
      system significantly facilitates specimen tracking, hospital cost reductions, and
      patient safety improvements. The success in our department is currently being
      replicated across all departments in our hospital that transport specimens. Our
      experience and strategy may be applied to inter-hospital specimen transportation
      in the future.

PMID- 24677009
TI  - [Reducing patient pressure sore incidence density in the pediatric surgical
      intensive care unit].
AB  - BACKGROUND & PROBLEMS: Our unit recorded 21 cases of pressure sores from January
      2011 to June 2011. The resulting pressure-sore incidence density of 0.74%
      exceeded the Taiwan Clinical Performance Indicator (TCPI) for medical centers
      (0.62%) as well as the mean incidence density for our unit (0.55%) during the
      same period in 2010. PURPOSE: We developed this project to decrease the incidence
      density of pressure sores at our pediatric-surgical-intensive-care unit from
      0.74% to 0.31%. RESOLUTIONS: Strategies implemented included: 1. providing on-the
      job education; 2. providing bedside teaching; 3. developing a series of pictures
      to illustrate proper sitting, lying, and changing positions and the proper
      fixation of catheters; 4. implementing a reminder mechanism; 5. introducing
      pressure-preventing devices; 6. and establishing an audit team. RESULTS:
      Incidence density decreased from 0.74% (Jan. to Jun. 2011) to 0.18% (Mar. to Jul.
      2012). CONCLUSIONS: We demonstrated that the developed improvement program
      effectively reduced the incidence density of pressure sores and increased the
      quality of nursing care.

PMID- 24677010
TI  - [Reducing the pain of intravenous injections in preschool children].
AB  - BACKGROUND & PROBLEMS: Peripheral intravenous catheter insertion is a significant
      source of stress for preschoolers during hospitalization. An average of about 85%
      of pediatric patients at our general pediatric unit are preschoolers. An average
      71% of these exhibit severe pain-related behavior during intravenous insertions.
      The factors influencing this pain experience may include inappropriate
      administration of analgesics by nurses, non-pharmacologic pain management, and
      inappropriate clinical settings. PURPOSE: This project worked to develop a
      strategy to reduce the incidence of severe injection pain in preschool children
      from 71.0% to 36.0% and to achieve a capacity improvement target of 50%.
      RESOLUTIONS: We implemented the following: 1) arranged a relevant training
      program for pediatric nurses; 2) revised hospital standards for pediatric
      intravenous insertions; and 3) enhanced analgesic administration and non
      pharmacologic pain management through creating child-friendly clinical settings
      and providing interactive toys. RESULTS: After implementing the above mentioned
      interventions, the incidence of severe pain-related behavior in pediatric
      patients decreased from 71.0% to 19.7%, a result that greatly exceeded
      expectations. CONCLUSIONS: This project demonstrated an effective approach to
      reducing severe intravenous-insertion pain in preschoolers and increasing
      pediatric care quality.

PMID- 24677011
TI  - [Project to decrease the nasogastric tube occlusion rate in a gastrointestinal
      unit].
AB  - BACKGROUND & PROBLEMS: When oral intake is inadequate or not recommended for
      patients with underlying diseases or specific treatments, it is common for these
      patients to receive nutrition enterally through a nasogastric tube. However, tube
      occlusion is a common complication of enteral feeding tubes. Data collected at
      our hospital from January to September 2011 identified 7 nasogastric tube
      occlusion events. All events were resolved by replacing the original tube with a
      new tube. PURPOSE: The purpose of this project was to reduce the nasogastric tube
      occlusion rate to 0.31% or less. RESOLUTIONS: Implemented interventions included:
      1) developing and administering a course for nurses on nasogastric-tube feeding
      techniques; (2) providing a filter for powdered medications; (3) developing a
      standard procedure for administering Nexium through nasogastric tubes; (4)
      updating patient-education pamphlets for nasogastric tube feeding; and (5)
      enhancing the quality of nurse auditing on nasogastric tube feeding techniques
      and nasogastric-tube medication-administration techniques. RESULTS: The average
      nasogastric tube occlusion rate decreased from 0.76% to 0% and the average
      nasogastric tube feeding technique compliance rate for nurses increased. The
      accuracy rate for specific medication administration techniques through
      nasogastric tubes increased dramatically from 16.7% to 100%. CONCLUSIONS: The
      project involved a multidisciplinary team of physicians, nurses, and pharmacists.
      This team developed a standard protocol for nasogastric tube feeding and specific
      medication administration recommendations for nasogastric tubes; revised nursing
      practice standards; and decreased the rate of nasogastric tube occlusion.

PMID- 24677012
TI  - [The effectiveness of care bundles in maintaining the skin integrity and reducing
      the incidence density of pressure ulcers in lung cancer inpatients].
AB  - BACKGROUND & PROBLEMS: Pressure ulcers are tissue defects that form on the skin
      as a result of progressive skin damage. Pressure ulcers are a skin-integrity
      related care issue and an important clinical indicator of care quality,
      especially for lung cancer inpatients who face rapidly deteriorating health
      conditions due to multiple symptoms and the side effects of treatment. Treating
      severe pressure ulcers may consume considerable manpower, time, and medical
      resources. Pressure ulcers may be avoided or effectively treated when nurses
      conduct proper skin assessments and care for wounds properly. PURPOSE: This
      project evaluates the efficacy of skin care bundles in terms of reducing the
      incidence density of pressure ulcers in lung cancer inpatients. RESOLUTION: Data
      gathered between January 2010 and March 2011 showed unstable incidence density
      for pressure ulcers. The average pressure-ulcer incidence density in lung cancer
      inpatients was 2.09%, which was 8-times higher than the average for all patients.
      Using evidence-based care bundles for pressure ulcer prevention, we trained nurse
      staffs to incorporate these bundles into their clinical daily care of lung cancer
      patients in our hospital. RESULTS: During the study period between November 2011
      and January 2012, the pressure-ulcer incidence density gradually fell to 0.55%.
      The incidence density continued to fall to 0.33% over the subsequent 8 months.
      CONCLUSIONS: We used the concept of "care bundles" to establish a standard skin
      care protocol for advanced lung cancer inpatients. This protocol improved the
      clinical ability of nursing staffs and effectively maintained skin care quality
      in lung cancer patients.

PMID- 24677013
TI  - Maternal serum analytes as predictors of IUGR with different degrees of placental
      vascular dysfunction.
AB  - OBJECTIVES: Our primary objective was to determine the association of maternal
      serum analytes in pregnancies complicated by intrauterine growth restriction
      (IUGR) stratified by umbilical artery (UA) Doppler versus pregnancies with
      appropriately grown for gestational age (AGA) and its potential use as screening
      model. METHODS: Retrospective cohort evaluating first and second trimester
      maternal serum aneuploidy screening markers in women complicated with IUGR [90
      with absent or reversed end diastolic velocity (AREDV), 46 with UA
      systolic/diastolic ratio >=95th percentile and 215 with normal UA Doppler] versus
      2590 women with AGA fetuses (control). RESULTS: Extreme levels of each analyte
      were significantly more common in the IUGR/AREDV group than in AGA group: inhibin
      A >97th percentile [>=2.27 multiples of the median (MoM)], OR: 41 (95% CI: 21
      80); unconjugated estriol <3rd percentile (<=0.6 MoM), OR: 17.2 (95% CI: 8.1-42);
      AFP >97th percentile (>=1.88 MoM), OR: 15 (95% CI: 8.2-27); PAPP-A <3rd
      percentile (<=0.33 MoM), OR: 13 (95% CI: 6.6-25.5); and free-beta human chorionic
      gonadotrophin second trimester >97th percentile (>=3.24 MoM), OR: 11.6 (95% CI:
      4.2-32). In a subgroup of pregnancies in which all markers were evaluated on each
      patient, a combination of abnormal markers detected 73% (95% CI: 54-87%) of
      IUGR/AREDV fetuses. When maternal risk factors were included into the risk
      calculation, it increased to 91% (95% CI: 76-98%). CONCLUSIONS: Abnormal maternal
      serum aneuploidy markers preferentially identify those pregnancies at greatest
      risk of IUGR with AREDV in the UA.

PMID- 24677014
TI  - Left Hemispheric Imbalance and Reward Mechanisms Affect Gambling Behavior: The
      Contribution of the Metacognition and Cortical Brain Oscillations.
AB  - The present research used the Iowa Gambling Task to test the effect of the reward
      sensitivity Behavioral Activation System-Reward (BAS-Reward) construct on the
      ability to distinguish between high- and low-risk decisions. To elucidate the
      individual differences that influence the decisional processes, making the
      strategies more or less advantageous, we considered the impact of the BAS
      motivational system and the frontal left and right cortical activity on subjects'
      decisions. More specifically, the lateralization effect, which is related to the
      increased activation of the left (BAS-Reward-related) hemisphere, was explored by
      using frequency band analysis. Specifically, behavioral responses (gain/loss
      options), metacognition, and delta, theta, alpha, and beta band modulation
      (asymmetry index) were considered. Thirty subjects were divided into high-BAS and
      low-BAS groups. In comparison with low-BAS, the high-BAS group showed an
      increased tendency to opt in favor of the immediate reward (losing strategy)
      instead of the long-term option (winning strategy), and members of this group
      were more impaired in metacognitive monitoring of their strategies and showed an
      increased left hemisphere activation when they responded to losing choices. A
      "reward bias" effect was hypothesized to act for high BAS, based on a left
      hemisphere hyperactivation. 

PMID- 24677015
TI  - Lack of Prominent Cognitive Regression in the Long-term Outcome of Patients
      Having Electrical Status Epilepticus During Sleep With Different Types of
      Epilepsy Syndromes.
AB  - The purpose was to document 4 patients with different epilepsy syndromes, showing
      electrical status epilepticus during sleep (ESES), without marked cognitive and
      behavioral regression in the long-term follow-up. The mean age at onset of
      seizures was 8 years. Absences, myoclonic, focal motor, or generalized tonic -
      clonic seizures and drop attacks were the prominent seizure types. The
      neurological examination and neuroimaging findings revealed no abnormality. Focal
      epileptiform electroencephalographic (EEG) activity was seen in 3 cases, whereas
      generalized photosensitive epileptic discharges were detected in 1 patient with
      juvenile myoclonic epilepsy. Neuropsychological evaluations of all cases were
      within the normal range, and deterioration in mental status was not observed
      during their mean follow-up duration of 14 years. Our data support the view that
      ESES can emerge along with different types of childhood epilepsy syndromes,
      including idiopathic generalized epilepsies, and may not always be a poor
      prognostic factor. 

PMID- 24677016
TI  - HIF-1alpha-induced HSP70 regulates anabolic responses in articular chondrocytes
      under hypoxic conditions.
AB  - We assessed whether heat shock protein 70 (HSP70) is involved in hypoxia
      inducible factor 1 alpha (HIF-1alpha)-dependent anabolic pathways in articular
      chondrocytes under hypoxic conditions. Primary rabbit chondrocytes were cultured
      under normoxia (20% oxygen condition) or hypoxia (1% oxygen condition).
      Alternatively, cells cultured under normoxia were treated with CoCl2 , which
      induces HIF-1alpha, to simulate hypoxia, or transfected with siRNAs targeting HIF
      1alpha (si-HIF-1alpha) and HSP70 (si-HSP70) under hypoxia. HSP70 expression was
      enhanced by the increased expression of HIF-1alpha under hypoxia or simulated
      hypoxia, but not in the presence of si-HIF-1alpha. Hypoxia-induced overexpression
      of ECM genes was significantly suppressed by si-HIF-1alpha or si-HSP70. Cell
      viability positively correlated with hypoxia, but transfection with si-HIF-1alpha
      or si-HSP70 abrogated the chondroprotective effects of hypoxia. Although LDH
      release from sodium nitroprusside-treated cells and the proportion of TUNEL
      positive cells were decreased under hypoxia, transfection with si-HIF-1alpha or
      si-HSP70 almost completely blocked these effects. These findings indicated that
      HIF-1alpha-induced HSP70 overexpression increased the expression levels of ECM
      genes and cell viability, and protected chondrocytes from apoptosis. HIF-1alpha
      may regulate the anabolic effects of chondrocytes under hypoxic conditions by
      regulating HSP70 expression.

PMID- 24677017
TI  - There is more to green reading than meets the eye! Exploring the gaze behaviours
      of expert golfers on a virtual golf putting task.
AB  - Gaze patterns and verbal reports of golfers at three skill levels (professional,
      elite amateur and club) were recorded as they read the slope of a virtual golf
      green from six different positions. The results showed that the professional
      golfers used a more economical gaze pattern consisting of fewer fixations of
      longer duration than the amateur and club players. Gaze pattern was accompanied
      by verbal reports that were not significantly more accurate in terms of aiming
      accuracy, although the professionals were accurate on 76.5 % of putts compared to
      57.1 % for the elite and club groups. Two read positions lead to more accurate
      predictions by the professional golfers only, suggesting distinctive periods of
      visual perceptual-cognitive attention may underly higher levels of putting skill.
      Theoretical implications of these results are discussed in relation to the
      application of visual attention theory to practise, as well as suggestions
      provided for further research.

PMID- 24677018
TI  - An evaluation of the potential for drug-drug interactions between bendamustine
      and rituximab in indolent non-Hodgkin lymphoma and mantle cell lymphoma.
AB  - PURPOSE: Bendamustine plus rituximab has been reported to be effective in
      treating lymphoid malignancies. This analysis investigated the potential for drug
      drug interactions between the drugs in patients with indolent non-Hodgkin
      lymphoma or mantle cell lymphoma. METHODS: Data were derived from a bendamustine
      rituximab combination therapy study, a bendamustine monotherapy study, and
      published literature on rituximab monotherapy and combination therapy. Analysis
      of the potential for rituximab to affect bendamustine systemic exposure included
      comparing bendamustine concentration-time profile following monotherapy to that
      following combination therapy and comparing model-predicted Bayesian bendamustine
      clearance in the presence and absence of rituximab. Analysis of the potential for
      bendamustine to affect rituximab systemic exposure included plotting observed
      minimum, median, and maximum serum rituximab concentrations at the end of
      rituximab infusion (EOI) and 24 h and 7 days post-infusion in patients receiving
      combination therapy versus concentrations reported in literature following
      rituximab monotherapy. RESULTS: The established population pharmacokinetic model
      following bendamustine monotherapy was evaluated to determine its applicability
      to combination therapy for the purpose of confirming lack of pharmacokinetic
      interaction. The model adequately described the bendamustine concentration-time
      profile following monotherapy and combination therapy in adults. There was no
      statistically significant difference in estimated bendamustine clearance either
      alone or in combination. Also, rituximab concentrations from EOI to 24 h and 7
      days demonstrated a pattern of decline similar to that seen in rituximab studies
      without bendamustine, suggesting that bendamustine does not affect the rituximab
      clearance rate. CONCLUSIONS: Neither bendamustine nor rituximab appears to affect
      systemic exposure of the other drug when coadministered.

PMID- 24677019
TI  - Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates
      experimental autoimmune encephalomyelitis in DBA/1 mice.
AB  - Microglia are resident antigen-presenting cells in the central nervous system
      (CNS) that either suppress or promote disease depending on their activation
      phenotype and the microenvironment. Multiple sclerosis (MS) is a chronic
      inflammatory disease causing demyelination and nerve loss in the CNS, and
      experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is
      widely used to investigate pathogenic mechanisms and therapeutic effects. We
      isolated and cultured microglia from adult mouse brains and exposed them to
      specific combinations of stimulatory molecules and cytokines, the combination of
      IL-4, IL-10, and TGF-beta yielding the optimal regime for induction of an
      immunosuppressive phenotype (M2). M2 microglia were characterized by decreased
      expression or production of CD86, PD-L1, nitric oxide, and IL-6, increased
      expression of PD-L2, and having a potent capacity to retain their phenotype on
      secondary proinflammatory stimulation. M2 microglia induced regulatory T cells,
      suppressed T-cell proliferation, and downmodulated M1-associated receptor
      expression in M1 macrophages. Myelin oligodendrocyte glycoprotein (MOG)-induced
      EAE was induced in DBA/1 mice and at different time points (0, 5, 12, or 15 days
      postimmunization) 3 * 105 M2 microglia were transferred intranasally. A single
      transfer of M2 microglia attenuated the severity of established EAE, which was
      particularly obvious when the cells were injected at 15 days postimmunization. M2
      microglia-treated mice had reduced inflammatory responses and less demyelination
      in the CNS. Our findings demonstrate that adult M2 microglia therapy represents a
      novel intervention that alleviated established EAE and that this therapeutic
      principle may have relevance for treatment of MS patients.

PMID- 24677021
TI  - Delayed diagnosis of subacute angle closure glaucoma in patients presenting with
      headaches.
AB  - Subacute angle closure glaucoma (SACG) may lead to chronic angle closure glaucoma
      and irreversible vision loss. Headaches may be the sole presenting symptom. This
      study characterizes the medical course and symptoms of patients with SACG in whom
      headache was the major symptom. This retrospective observational study consisted
      of 30 consecutive patients, suffering from headaches and diagnosed with SACG,
      collected from the Glaucoma Service at the Ophthalmology Department of Meir
      Medical Center, Kfar Saba, Israel, a tertiary care referral facility. The primary
      study outcomes were reasons for referral, number of specialists visited and
      number of imaging studies performed before diagnosing SACG and headache
      characteristics. The majority of the patients experienced headaches once or twice
      a week. Four patients suffered a classic SACG pain involving the eye and frontal
      or hemicranial area. The mean time from onset of headaches to diagnosis was 2.6
      years. The main reason for referral to the glaucoma clinic was consultation (53
      %), and SACG was suspected by the referring physicians in two patients. Seventy
      three percent of the patients were referred to at least three physicians in
      various medical specialties prior to referral to the glaucoma clinic. Patients
      usually do not volunteer history regarding headaches and clinicians often do not
      associate headaches with SACG in the absence of ocular symptoms. SACG should be
      included in the differential diagnosis in individuals older than 40 years
      presenting with late onset of headaches. Such patients should be referred to an
      ophthalmologist. 

PMID- 24677022
TI  - Blepharospasm in familial AD secondary to an APP mutation (V715M).

PMID- 24677020
TI  - Sox18 preserves the pulmonary endothelial barrier under conditions of increased
      shear stress.
AB  - Shear stress secondary to increased pulmonary blood flow (PBF) is elevated in
      some children born with congenital cardiac abnormalities. However, the majority
      of these patients do not develop pulmonary edema, despite high levels of
      permeability inducing factors. Previous studies have suggested that laminar fluid
      shear stress can enhance pulmonary vascular barrier integrity. However, little is
      known about the mechanisms by which this occurs. Using microarray analysis, we
      have previously shown that Sox18, a transcription factor involved in blood vessel
      development and endothelial barrier integrity, is up-regulated in an ovine model
      of congenital heart disease with increased PBF (shunt). By subjecting ovine
      pulmonary arterial endothelial cells (PAEC) to laminar flow (20 dyn/cm(2) ), we
      identified an increase in trans-endothelial resistance (TER) across the PAEC
      monolayer that correlated with an increase in Sox18 expression. Further, the TER
      was also enhanced when Sox18 was over-expressed and attenuated when Sox18
      expression was reduced, suggesting that Sox18 maintains the endothelial barrier
      integrity in response to shear stress. Further, we found that shear stress up
      regulates the cellular tight junction protein, Claudin-5, in a Sox18 dependent
      manner, and Claudin-5 depletion abolished the Sox18 mediated increase in TER in
      response to shear stress. Finally, utilizing peripheral lung tissue of 4 week old
      shunt lambs with increased PBF, we found that both Sox18 and Claudin-5 mRNA and
      protein levels were elevated. In conclusion, these novel findings suggest that
      increased laminar flow protects endothelial barrier function via Sox18 dependent
      up-regulation of Claudin-5 expression.

PMID- 24677023
TI  - [A large cystic tumor in the right lower abdomen].

PMID- 24677025
TI  - Detection of peptidic erythropoiesis-stimulating agents in sport.
AB  - Detection methods for erythropoiesis-stimulating agents in sport can be
      classified into direct and indirect approaches. Direct methods comprise
      electrophoretic techniques (isoelectric focusing (IEF-), sodium-dodecylsulfate
      (SDS-), sarcosyl (SAR-) polyacrylamide gel-electrophoreses (-PAGE)), ELISAs and
      mass spectrometric methods. The haematological module of the Athlete Biological
      Passport is currently the only applied indirect approach. Newer developments
      include a mass spectrometric test for peginesatide, sequential exoglycosidase
      digestion of ertythropoietin (EPO) combined with electrophoresis (SDS/SAR-PAGE),
      a dipstick method (MAIIA), and a study on the differences in sialic acid O
      acetylation of tryptic EPO O-glycopeptides. The focus of this article is on
      direct detection methods. 

PMID- 24677024
TI  - Dopamine differently modulates central cholinergic circuits in patients with
      Alzheimer disease and CADASIL.
AB  - Short-latency afferent inhibition (SAI) technique gives the opportunity to non
      invasively test an inhibitory circuit in the human cerebral motor cortex that
      depends mainly on central cholinergic activity. Important SAI abnormalities have
      been reported in both patients with Alzheimer disease (AD) and cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a
      normalization of SAI was observed in AD after levo-dopa (L-dopa) administration.
      We aimed to determine whether the pharmacological manipulation of the
      dopaminergic system can also interfere with SAI test in CADASIL patients,
      compared with AD patients and healthy controls. SAI was found to be significantly
      reduced in both patient groups. L-Dopa significantly increased SAI in the AD
      patients, while it failed to restore SAI abnormality in CADASIL patients.
      Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific
      effect. The present study supports the notion that relationship between
      acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa
      challenge may thus be able to differentiate the patients with AD or a mixed form
      of dementia from those with "pure" VD. 

PMID- 24677026
TI  - Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator
      cuff tendon: a mechanism underpinning the ultimately deleterious effect of
      steroid injection in tendinopathy?
AB  - BACKGROUND: Glucocorticoid injection (GCI) and surgical rotator cuff repair are
      two widely used treatments for rotator cuff tendinopathy. Little is known about
      the way in which medical and surgical treatments affect the human rotator cuff
      tendon in vivo. We assessed the histological and immunohistochemical effects of
      these common treatments on the rotator cuff tendon. STUDY DESIGN: Controlled
      laboratory study. METHODS: Supraspinatus tendon biopsies were taken before and
      after treatment from 12 patients undergoing GCI and 8 patients undergoing
      surgical rotator cuff repair. All patients were symptomatic and none of the
      patients undergoing local GCI had full thickness tears of the rotator cuff. The
      tendon tissue was then analysed using histological techniques and
      immunohistochemistry. RESULTS: There was a significant increase in nuclei count
      and vascularity after rotator cuff repair and not after GCI (both p=0.008).
      Hypoxia inducible factor 1alpha (HIF-1alpha) and cell proliferation were only
      increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic N
      methyl-d-aspartate receptor 1 (NMDAR1) glutamate receptor was only increased
      after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was
      seen in both groups following treatment (both p=0.04), while an increase in the
      receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator
      cuff repair (p=0.016). CONCLUSIONS: The increases in cell proliferation,
      vascularity and HIF-1alpha after surgical rotator cuff repair appear consistent
      with a proliferative healing response, and these features are not seen after GCI.
      The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the
      potential excitotoxic tendon damage that may result from this common treatment.

PMID- 24677027
TI  - Fertility and apparent genetic anticipation in Lynch syndrome.
AB  - Genetic anticipation is the phenomenon in which age of onset of an inherited
      disorder decreases in successive generations. Inconsistent evidence suggests that
      this occurs in Lynch syndrome. A possible cause for apparent anticipation is
      fecundity bias, which occurs if the disease adversely affects fertility. The
      purpose of this study was to determine the effect of age of diagnosis of
      colorectal cancer (CRC) on lifetime fertility in Lynch syndrome, and whether this
      can falsely create the appearance of genetic anticipation. A computer model
      simulated age of diagnosis of CRC in hypothetical Lynch syndrome carriers and
      their offspring. The model assumed similar age distribution of CRC across
      generations (i.e. that there was no true anticipation). Age distribution of CRC
      diagnosis, and lifetime fertility rates (grouped by age of diagnosis of CRC) were
      determined from the Australasian Colorectal Cancer Family Registry (ACCFR).
      Apparent anticipation was calculated by comparing ages of diagnosis of CRC in
      affected parent-child pairs. A total of 1,088 patients with CRC were identified
      from the ACCFR. Total lifetime (cohort) fertility was related to age of diagnosis
      of CRC (correlation coefficient 0.13, P = 0.0001). In the simulation, apparent
      anticipation was 1.8 +/- 0.54 years (P = 0.0044). Observed apparent anticipation
      in the ACCFR cohort was 4.8 +/- 1.73 years (P = 0.0064). There was no difference
      in apparent anticipation between the simulate d and observed parent-child pairs
      (P = 0.89). The appearance of genetic anticipation in Lynch syndrome can be
      falsely created due to changes in fertility. 

PMID- 24677028
TI  - Feasibility, efficacy, and adverse effects of outpatient antibacterial
      prophylaxis in children with acute myeloid leukemia.
AB  - BACKGROUND: Intensive chemotherapy for pediatric acute myeloid leukemia incurs
      the risk of infectious complications, but the benefits of antibiotic prophylaxis
      remain unclear. METHODS: In the current study, among 103 children treated on the
      AML02 protocol between October 2002 and October 2008 at St. Jude Children's
      Research Hospital, the authors retrospectively assessed the effect of antibiotic
      prophylaxis on the frequency of febrile neutropenia, clinically or
      microbiologically confirmed infections (including bacteremia), and antibiotic
      resistance, as well as on the results of nasal and rectal surveillance cultures.
      Initially, patients received no prophylaxis or oral cephalosporin (group A). The
      protocol was then amended to administer intravenous cefepime alone or intravenous
      vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous
      cefepime (group B). RESULTS: There were 334 infectious episodes. Patients in
      group A had a significantly greater frequency of documented infections and
      bacteremia (both P < .0001) (including gram-positive and gram-negative
      bacteremia; P = .0003 and .001, respectively) compared with patients in group B,
      especially viridans streptococcal bacteremia (P = .001). The incidence of febrile
      neutropenia without documented infection was not found to be different between
      the 2 groups. Five cases of bacteremia with vancomycin-resistant enterococci
      (VRE) occurred in group B (vs none in group A), without related mortality. Two of
      these cases were preceded by positive VRE rectal surveillance cultures.
      CONCLUSIONS: Outpatient intravenous antibiotic prophylaxis is feasible in
      children with acute myeloid leukemia and reduces the frequency of documented
      infection but not of febrile neutropenia. Despite the emergence of VRE
      bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to
      shorten the duration of prophylaxis and thereby minimize resistance should be
      explored.

PMID- 24677029
TI  - Numerical compression schemes for proteomics mass spectrometry data.
AB  - The open XML format mzML, used for representation of MS data, is pivotal for the
      development of platform-independent MS analysis software. Although conversion
      from vendor formats to mzML must take place on a platform on which the vendor
      libraries are available (i.e. Windows), once mzML files have been generated, they
      can be used on any platform. However, the mzML format has turned out to be less
      efficient than vendor formats. In many cases, the naive mzML representation is
      fourfold or even up to 18-fold larger compared with the original vendor file. In
      disk I/O limited setups, a larger data file also leads to longer processing
      times, which is a problem given the data production rates of modern mass
      spectrometers. In an attempt to reduce this problem, we here present a family of
      numerical compression algorithms called MS-Numpress, intended for efficient
      compression of MS data. To facilitate ease of adoption, the algorithms target the
      binary data in the mzML standard, and support in main proteomics tools is already
      available. Using a test set of 10 representative MS data files we demonstrate
      typical file size decreases of 90% when combined with traditional compression, as
      well as read time decreases of up to 50%. It is envisaged that these improvements
      will be beneficial for data handling within the MS community. 

PMID- 24677031
TI  - Engineering a DNA-cleaving DNAzyme and PCR into a simple sensor for zinc ion
      detection.
AB  - The development of a simple sensor (9NL27-Zn) based on DNAzyme and PCR and aimed
      at the detection of low concentrations of zinc (II) ions is described. A specific
      Zn(II)-dependent DNAzyme (9NL27) with DNA-cleaving activity was employed. In the
      presence of zinc (II), the DNAzyme hydrolyzed DNA substrate into two pieces (5'
      and 3' fragments), forming 3'-terminal hydroxyl in the 5' fragment and 5'
      phosphate in the 3' fragments. Subsequently, the 5' fragment left the DNAzyme and
      bound a short DNA template. The 5' fragment was used as a primer and extended a
      single-stranded full-length template by Taq polymerase. Finally, this full-length
      template was amplified by PCR. The amplified products had a quantitative
      relationship with Zn(II) concentration. Under our experimental conditions, the
      DNA sensor showed sensitivity (10 nM) and high specificity for zinc ion
      detection. After improvement of the DNA sensor, the detection limit can reach 1
      nM. The simple DNA sensor may become a DNA model for the detection of trace
      amounts of other targets.

PMID- 24677030
TI  - Daily rhythms in the cyanobacterium synechococcus elongatus probed by high
      resolution mass spectrometry-based proteomics reveals a small defined set of
      cyclic proteins.
AB  - Circadian rhythms are self-sustained and adjustable cycles, typically entrained
      with light/dark and/or temperature cycles. These rhythms are present in animals,
      plants, fungi, and several bacteria. The central mechanism behind these
      "pacemakers" and the connection to the circadian regulated pathways are still
      poorly understood. The circadian rhythm of the cyanobacterium Synechococcus
      elongatus PCC 7942 (S. elongatus) is highly robust and controlled by only three
      proteins, KaiA, KaiB, and KaiC. This central clock system has been extensively
      studied functionally and structurally and can be reconstituted in vitro. These
      characteristics, together with a relatively small genome (2.7 Mbp), make S.
      elongatus an ideal model system for the study of circadian rhythms. Different
      approaches have been used to reveal the influence of the central S. elongatus
      clock on rhythmic gene expression, rhythmic mRNA abundance, rhythmic DNA topology
      changes, and cell division. However, a global analysis of its proteome dynamics
      has not been reported yet. To uncover the variation in protein abundances during
      48 h under light and dark cycles (12:12 h), we used quantitative proteomics, with
      TMT 6-plex isobaric labeling. We queried the S. elongatus proteome at 10
      different time points spanning a single 24-h period, leading to 20 time points
      over the full 48-h period. Employing multidimensional separation and high
      resolution mass spectrometry, we were able to find evidence for a total of 82% of
      the S. elongatus proteome. Of the 1537 proteins quantified over the time course
      of the experiment, only 77 underwent significant cyclic variations.
      Interestingly, our data provide evidence for in- and out-of-phase correlation
      between mRNA and protein levels for a set of specific genes and proteins. As a
      range of cyclic proteins are functionally not well annotated, this work provides
      a resource for further studies to explore the role of these proteins in the
      cyanobacterial circadian rhythm. 

PMID- 24677032
TI  - Determination of lewisite metabolite 2-chlorovinylarsonous acid in urine by use
      of dispersive derivatization liquid-liquid microextraction followed by gas
      chromatography-mass spectrometry.
AB  - The purpose of this study was to develop a sensitive and simple method, based on
      dispersive derivatization liquid-liquid microextraction-gas chromatography-mass
      spectrometry (DDLLME-GC-MS) in scanning and selected-ion-monitoring (SIM) modes,
      for detection of 2-chlorovinylarsonous acid (CVAA) as a hydrolysis product and
      urinary metabolite of lewisite in urine samples. Chloroform (65 MUL), methanol
      (500 MUL), and ethanedithiol (10 MUL) were used as extraction solvent, dispersive
      solvent, and derivatizing reagent, respectively. Critical conditions of the
      proposed method were optimized. The nucleophilic reactions of dithiol and
      monothiol compounds with CVAA were also studied using a competitive method. In
      view of the high affinity of trivalent arsenic for sulfhydryl groups, the
      interaction between CVAA and bis(2-chlorovinyl)arsonous acid (BCVAA) and free
      cysteine (Cys) was also investigated using liquid chromatography-electrospray
      ionization mass spectrometry (LC-ESI-MS). The interference of Cys, present in
      human urine, with the detection of CVAA was evaluated using dithiol and monothiol
      chemicals as derivatization agents. The developed method provided a
      preconcentration factor of 250, and limits of detection of 0.015 and 0.30 MUg L(
      1) in SIM and scanning modes, respectively. The calibration curves were linear
      over the concentration range of 1-400 MUg L(-1) in full-scan mode. The relative
      standard deviation (RSD) values were calculated to be 5.5 and 3.2% at
      concentrations of 20 and 100 MUg L(-1), respectively. Collision-induced
      dissociation studies of the major electron-impact (EI) ions were performed to
      confirm the proposed fragment structure of CVAA-dithiols derivatives. Results
      indicated that the developed method for analysis of CVAA is suitable not only for
      verification of human exposure to lewisite, but also for quantification of CVAA
      in urine samples.

PMID- 24677033
TI  - A double-blind, placebo-controlled phase II study of the efficacy and safety of
      2,2-dimethylbutyrate (HQK-1001), an oral fetal globin inducer, in sickle cell
      disease.
AB  - This placebo-controlled phase II study evaluated the pharmacodynamics, efficacy
      and safety of 2,2-dimethylbutyrate (HQK-1001), a fetal globin gene-inducing short
      chain fatty acid derivative, administered orally at 15 mg/kg twice daily for 48
      weeks in 76 subjects with sickle cell disease (SCD). The median age was 26 years
      (range: 12-55 years) and 37 subjects (49%) were treated previously with
      hydroxycarbamide. Sixty subjects (79%) had Hb SS and 16 (21%) had S/beta(0)
      thalassemia. The study was terminated after a planned interim analysis showed no
      significant increase in fetal hemoglobin (Hb F) and a trend for more pain crises
      in the HQK-1001 group. For 54 subjects with Week 24 data, the mean absolute
      increase in Hb F was 0.9% (95% confidence interval (CI): 0.1-1.6%) with HQK-1001
      and 0.2% (95% CI: -0.7-1.1%) with placebo. Absolute increases in Hb F greater
      than 3% were noted in 9 of 38 subjects (24%) administered HQK-1001 and 1 of 38
      subjects (3%) administered placebo. The mean changes in hemoglobin at Week 24
      were comparable between the two groups. The mean annualized rate of pain crises
      was 3.5 with HQK-1001 and 1.7 with placebo. The most common adverse events in the
      HQK-1001 group, usually graded as mild or moderate, consisted of nausea,
      headache, vomiting, abdominal pain, and fatigue. Additional studies of HQK-1001
      at this dose and schedule are not recommended in SCD. Intermittent HQK-1001
      administration, rather than a daily regimen, may be better tolerated and more
      effective, as shown previously with arginine butyrate, and warrants further
      evaluation.

PMID- 24677034
TI  - Target site pharmacokinetics of linezolid after single and multiple doses in
      diabetic patients with soft tissue infection.
AB  - The underlying pathology of diabetic wounds, i.e. impairment of macro- and
      microcirculation, might also impact target site penetration of antibacterial
      drugs. To compare tissue concentrations of linezolid in infected and not infected
      tissue 10 patients suffering from type 2 diabetes with foot infection were
      included in the study. Tissue penetration of linezolid was assessed using in vivo
      microdialysis at the site of infection as well as in non-inflamed subcutaneous
      adipose tissue. All patients were investigated after receiving a single dose of
      linezolid and five patients in addition at steady state. After a single dose of
      linezolid significantly higher area under the concentration vs. time curve over 8
      hours (AUC0-8 ) and maximum concentrations (Cmax )-values were observed in plasma
      (65.5 +/- 21.2 mg*h/L and 16.4 +/- 4.6 mg/L) as compared to inflamed (36.3 +/-
      22.9  mg*h/L and 6.6 +/- 3.6 mg/L) and non-inflamed tissue (33.0 +/- 17.7 mg*h/L
      and 6.7 +/- 3.6 mg/L). Multiple administrations of linezolid led to disappearance
      of significant differences in Cmax and AUC0-8 between plasma, inflamed, and non
      inflamed tissue. Approximately 2-fold increase of Cmax and AUC0-8 -values in
      tissue was observed at steady state as compared to the first administration.
      Penetration of linezolid is not impaired in diabetic foot infection but
      equilibrium between plasma and tissue might be delayed. 

PMID- 24677036
TI  - Framework for assessing the capacity of a health ministry to conduct health
      policy processes--a case study from Tajikistan.
AB  - An adequate capacity of ministries of health (MOH) to develop and implement
      policies is essential. However, no frameworks were found assessing MOH capacity
      to conduct health policy processes within developing countries. This paper
      presents a conceptual framework for assessing MOH capacity to conduct policy
      processes based on a study from Tajikistan, a former Soviet republic where
      independence highlighted capacity challenges. The data collection for this
      qualitative study included in-depth interviews, document reviews and observations
      of policy events. Framework approach for analysis was used. The conceptual
      framework was informed by existing literature, guided the data collection and
      analysis, and was subsequently refined following insights from the study. The
      Tajik MOH capacity, while gradually improving, remains weak. There is poor
      recognition of wider contextual influences, ineffective leadership and governance
      as reflected in centralised decision-making, limited use of evidence, inadequate
      actors' participation and ineffective use of resources to conduct policy
      processes. However, the question is whether this is a reflection of lack of MOH
      ability or evidence of constraining environment or both. The conceptual framework
      identifies five determinants of robust policy processes, each with specific
      capacity needs: policy context, MOH leadership and governance, involvement of
      policy actors, the role of evidence and effective resource use for policy
      processes. Three underlying considerations are important for applying the
      capacity to policy processes: the need for clear focus, recognition of capacity
      levels and elements, and both ability and enabling environment. The proposed
      framework can be used in assessing and strengthening of the capacity of different
      policy actors.

PMID- 24677037
TI  - A novel biologically inspired local feature descriptor.
AB  - Local feature descriptor is a fundamental representation for image patch which
      has been extensively used in many computer vision applications. In this paper,
      different from state-of-the-art features, a novel biologically inspired local
      descriptor (BILD) is proposed based on the visual information processing
      mechanism of ventral pathway in human brain. The local features used for
      constructing BILD are extracted by a two-layer network, which corresponds to the
      simple-to-complex cell hierarchy in the primary visual cortex (V1). It works in a
      similar way as the simple cell and complex cell do to get responses by applying
      the lateral inhibition from different orientations and operating an improved
      cortical pooling. To enhance the distinctiveness of BILD, we combine the local
      features from different orientations. Extensive evaluations have been performed
      for image matching and object recognition. Experimental results reveal that our
      proposed BILD outperforms many widely used descriptors such as SIFT and SURF,
      which demonstrate its efficiency for representing local regions. 

PMID- 24677038
TI  - Emotions in robot psychology.
AB  - In his famous thought experiments on synthetic vehicles, Valentino Braitenberg
      stipulated that simple stimulus-response reactions in an organism could evoke the
      appearance of complex behavior, which, to the unsuspecting human observer, may
      even appear to be driven by emotions such as fear, aggression, and even love
      (Braitenberg, Vehikel. Experimente mit kunstlichen Wesen, Lit Verlag, 2004). In
      fact, humans appear to have a strong propensity to anthropomorphize, driven by
      our inherent desire for predictability that will quickly lead us to discern
      patterns, cause-and-effect relationships, and yes, emotions, in animated
      entities, be they natural or artificial. But might there be reasons, that we
      should intentionally "implement" emotions into artificial entities, such as
      robots? How would we proceed in creating robot emotions? And what, if any, are
      the ethical implications of creating "emotional" robots? The following article
      aims to shed some light on these questions with a multi-disciplinary review of
      recent empirical investigations into the various facets of emotions in robot
      psychology.

PMID- 24677035
TI  - Simple derivation of transgene-free iPS cells by a dual recombinase approach.
AB  - Mammalian cells can be reprogrammed into induced pluripotent stem cells (iPSCs),
      a valuable tool for in vitro disease modeling and regenerative medicine. These
      applications demand for iPSCs devoid of reprogramming factor transgenes, but
      current procedures for the derivation of transgene-free iPSCs are inefficient and
      cumbersome. Here, we describe a new approach for the simple derivation of
      transgene-free iPSCs by the sequential use of two DNA recombinases, C31 Integrase
      and Cre, to control the genomic insertion and excision of a single, non-viral
      reprogramming vector. We show that such transgene-free iPSCs exhibit gene
      expression profiles and pluripotent developmental potential comparable to
      genuine, blastocyst-derived embryonic stem cells. As shown by a reporter iPSC
      line for the differentiation into midbrain dopaminergic neurons, the dual
      recombinase approach offers a simple and efficient way to derive transgene-free
      iPSCs for studying disease mechanisms and cell replacement therapies.

PMID- 24677039
TI  - Improvement of erythrose reductase activity, deletion of by-products and
      statistical media optimization for enhanced erythritol production from Yarrowia
      lipolytica mutant 49.
AB  - The purpose of the present investigation was to produce erythritol by Yarrowia
      lipolytica mutant without any by-products. Mutants of Y. lipolytica were
      generated by ultra-violet for enhancing erythrose reductase (ER) activity and
      erythritol production. The mutants showing the highest ER activity were screened
      by triphenyl tetrazolium chloride agar plate assay. Productivity of samples was
      analyzed by thin-layer chromatography and high-performance liquid chromatography
      equipped with the refractive index detector. One of the mutants named as mutant
      49 gave maximum erythritol production without any other by-products (particularly
      glycerol). Erythritol production and specific ER activity in mutant 49 increased
      to 1.65 and 1.47 times, respectively, in comparison with wild-type strain. The ER
      gene of wild and mutant strains was sequenced and analyzed. A general comparison
      of wild and mutant gene sequences showed the replacement of Asp(270) with
      Glu(270) in ER protein. In order to enhance erythritol production, we used a
      three component-three level-one response Box-Behnken of response surface
      methodology model. The optimum medium composition for erythritol production was
      found to be (g/l) glucose 279.49, ammonium sulfate 9.28, and pH 5.41 with 39.76
      erythritol production. 

PMID- 24677040
TI  - Bombyx mori nucleopolyhedrovirus ORF101 encodes a budded virus envelope
      associated protein.
AB  - Orf101 (Bm101) of Bombyx mori nucleopolyhedrovirus (BmNPV) is a highly conserved
      gene in lepidopteran nucleopolyhedroviruses, but its function remains unknown. In
      this study, Bm101 was characterized. Transcripts of Bm101 were detected from 24
      through 96 h post infection (h p.i.) by RT-PCR. The corresponding protein was
      also detected from 24 to 96 h p.i. in BmNPV-infected BmN cells by Western blot
      analysis using a polyclonal antibody against Bm101. Western blot assay of
      occlusion-derived virus and budded virus (BV) preparations revealed that Bm101
      encodes a 28-kDa structural protein that is associated with BV and is located in
      the envelope fraction of budded virions. In addition, confocal analysis showed
      that the protein was localized in the cytosol and cytoplasmic membrane in virus
      infected cells. In conclusion, the available data suggest that Bm101 is a
      functional ORF of BmNPV and encodes a protein expressed in the late stage of the
      infection cycle that is associated with the BV envelope. 

PMID- 24677041
TI  - Interactions between Kluyveromyces marxianus and Saccharomyces cerevisiae in
      tequila must type medium fermentation.
AB  - Traditional tequila fermentation is a complex microbial process performed by
      different indigenous yeast species. Usually, they are classified in two families:
      Saccharomyces and Non-Saccharomyces species. Using mixed starter cultures of
      several yeasts genera and species is nowadays considered to be beneficial to
      enhance the sensorial characteristics of the final products (taste, odor).
      However, microbial interactions occurring in such fermentations need to be better
      understood to improve the process. In this work, we focussed on a Saccharomyces
      cerevisiae/Kluyveromyces marxianus yeast couple. Indirect interactions due to
      excreted metabolites, thanks to the use of a specific membrane bioreactor, and
      direct interaction due to cell-to-cell contact have been explored. Comparison of
      pure and mixed cultures was done in each case. Mixed cultures in direct contact
      showed that both yeast were affected but Saccharomyces rapidly dominated the
      cultures whereas Kluyveromyces almost disappeared. In mixed cultures with
      indirect contact the growth of Kluyveromyces was decreased compared to its pure
      culture but its concentration could be maintained whereas the growth of
      Saccharomyces was enhanced. The loss of viability of Kluyveromyces could not be
      attributed only to ethanol. The sugar consumption and ethanol production in both
      cases were similar. Thus the interaction phenomena between the two yeasts are
      different in direct and indirect contact, Kluyveromyces being always much more
      affected than Saccharomyces. 

PMID- 24677042
TI  - Modified Charles procedure and lymph node flap transfer for advanced lower
      extremity lymphedema.
AB  - INTRODUCTION: Treatment of advanced lymphedema remains a challenge in
      reconstructive surgery. Microsurgical techniques seem to be effective in early
      stage lymphedema, however in advanced stages their role is not well established.
      In this study, we present a novel approach for advanced lymphedema combining
      excisional procedure (Charles) with transferring lymph node flap. PATIENTS AND
      METHOD: From 2010 to 2013, 24 patients (18 women, six men, mean age 53 years old)
      presented with late stage of lower extremity lymphedema. The modification of
      Charles procedure consisted of preserving the superficial venous system of the
      dorsum of the foot and the lesser saphenous vein, which were used for the venous
      anastomosis of the transferred lymph node flap. In 11 patients we transferred the
      inguinal lymph node flaps from the contralateral site, meanwhile in 13 patients
      supraclavicular lymph node flaps were used. RESULTS: Maximum reduction of the
      lymphedema was achieved. No major complication was detected postoperatively.
      There were two patients with partial loss of the skin graft necessitated re
      grafting. All the lymph node flaps survived well. The patients resumed normal
      daily activities within a period of 2 months. The mean follow-up was 14 months (3
      26 months). During this period, no recurrence of the lymphedema was observed.
      CONCLUSION: The combination of the modified Charles procedure with vascularized
      transferring of lymph node flap is an effective method for treatment of advanced
      stage lymphedema.

PMID- 24677043
TI  - [Large asymptomatic cardiac lipoma localised in superior vena cava inflow: three
      year follow-up].

PMID- 24677044
TI  - Successful surgery for lateral left ventricular wall rupture with severe mitral
      insufficiency resulting in cardiogenic shock.

PMID- 24677045
TI  - Dynamic left ventricular outflow tract obstruction.

PMID- 24677046
TI  - Duplex Doppler ultrasound examination of carotid and vertebral arteries:
      guidelines of the Polish Society for Vascular Surgery.
AB  - The duplex Doppler examination of carotid and vertebral arteries is the primary
      diagnostic method in detecting disorders leading to the brain blood supply
      disturbances. In many cases, in patients with carotid artery stenosis, the
      Doppler ultrasound plays a major role in the process of qualification to the
      reconstructive procedures. Regardless of the widespread availability and high
      sensitivity and specificity of this method it's burdened with serious drawbacks.
      The most important of them are evaluation subjectivity and variety of methods to
      assess stenosis degree and the nature of atherosclerotic plaques. They often
      cause difficulties in comparing the test results carried out in different centers
      and to find correlations with other imaging methods results. In order to overcome
      these drawbacks, Polish Society for Vascular Surgery has attempted to develop
      recommendations for uniform methodology of carotid and vertebral arteries Doppler
      examination. Legal terms, the manner of examination and its interpretation were
      presented. Proposing the way of highlights results and messages conclusion to
      enable the recommendationsimplementation of endovascular and surgical
      qualifications relating to surgical treatment. We hope that these recommendations
      will help to standardize examination techniques. 

PMID- 24677047
TI  - Changes in digestive enzyme activities of red porgy Pagrus pagrus during a
      fasting-refeeding experiment.
AB  - An experiment was carried out in red porgy, Pagrus pagrus (Teleostei, Sparidae),
      to assess the effects of a 14-day fasting period, followed by refeeding to
      apparent satiation, on the contents of digestive enzymes (total proteases, and
      particularly pepsin, trypsin, chymotrypsin, carboxypeptidases A and B; amylase
      and lipase). Two fish groups were considered: one (indicated as fasted/refed
      group) was fasted for 14 days and then refed during further 7 and 15 days, and
      the other was fed throughout the study and was taken as a control group. The
      measured enzymatic values showed that fasting resulted in a generalized, not
      significant decrease, of the activity of digestive enzymes. Refeeding caused a
      significant increase for most of the assayed enzymes: total proteases both in the
      middle and distal intestine, pepsin in the stomach, trypsin in the middle
      intestine, and amylase and lipase in the proximal intestine. Nevertheless, the
      detection in the fasted/refed fish of enzymatic values still lower than those
      measured in the control fish suggested that fish experiencing short-term fasting
      were partially impaired in their digestive capacity.

PMID- 24677048
TI  - Protease in sturgeon sperm and the effects of protease inhibitors on sperm
      motility and velocity.
AB  - In mammals, proteases are present in sperm acrosome and play key role in
      fertilization. Sturgeon sperm has an acrosome, but its physiology, biochemistry,
      and potential role in fertilization are unknown. In the present study, we have
      observed high protease activity in acidic extract of intact sperm compared to
      that of seminal plasma in sterlet (Acipenser ruthenus). The protease activity was
      decreased and increased in acidic extract of motility-activated sperm and in the
      activation medium, respectively. Molecular analysis revealed total protease and
      serine (acrosin) protease activities in sperm acidic extract which was
      accumulated in a protein band with relative molecular mass of 35 kDa.
      Immunoelectron microscopy using an affinity-purified polyclonal antibody for boar
      acrosin localized the protease at the acrosome region. Moreover, initiation of
      sperm motility was inhibited after activation in the presence of inhibitors for
      both trypsin-like and chymotrypsin-like proteases, while the effects of protease
      inhibitors on sperm velocity were uncertain. Our results indicate similarities in
      physiology and biochemistry of acrosome between sturgeon and mammals and suggest
      potential role of protease in the initiation of sperm motility in sturgeon.

PMID- 24677049
TI  - [Unilateral leg swelling after minimally invasive disc surgery in a 57-year-old
      woman].
AB  - Unilateral leg swelling is most frequently the result of venous hypertension
      based on deep vein thrombosis. The suspicion of a pelvic vein thrombosis requires
      direct thrombus detection and exclusion of the spectrum of differential
      diagnoses, especially after pelvic surgery. In this paper we report a case of
      unilateral leg swelling with complex arteriovenous vascular pathology after
      minimally invasive disc surgery. The differential diagnosis and interventional
      therapy are discussed. 

PMID- 24677050
TI  - Extracellular lipase of an entomopathogenic fungus effecting larvae of a scale
      insect.
AB  - Lipases play an important role in the infection process of entomopathogenic fungi
      by hydrolyzing the ester bonds of lipoproteins, fats and waxes present on the
      insect surface and in the body. Here we report the purification and
      characterization of an extracellular lipase from Isaria fumosorosea. The enzyme
      was purified (138.46-fold) in three steps using (NH4 )2 SO4 precipitation
      followed by DEAE-cellulose and Sephadex G-100 column chromatography. The
      molecular weight of purified enzyme was determined to be 31 KDa by SDS-PAGE. The
      optimum temperature and pH for enzyme activity were 35  degrees C and 7.0,
      respectively, using p-nitrophenylpalmitate as the substrate. Lipolytic activity
      was enhanced in the presence of Ca(+2) , Mg(+2) , Na(+) , and NH4 (+) salts,
      while Zn(+2) , Fe(+2) , and Cu(+2) inhibited enzyme activity. The enzyme
      displayed broad substrate specificity with the highest activity observed for
      coconut oil and p-nitrophenyl carprate. Topical co-application of purified lipase
      with fungal conidial suspensions decreased the median survival time (ST50 ) of
      Dysmicoccus neobrevipes nymphs as compared to the fungus alone. Our results
      indicate that an extracellular lipase produced by I. fumosorosea can be exploited
      for development of enzyme-based insect management. 

PMID- 24677052
TI  - Predictive factors of bacteremia in patients with febrile urinary tract
      infection: an experience at a tertiary care center.
AB  - PURPOSE: To investigate the clinical features in adult patients with febrile
      urinary tract infection (UTI) who visited the emergency department (ED) and to
      determine the predictive factors of bacteremia among the initial presenting
      clinical features. METHODS: This retrospective cohort study was conducted at the
      ED of a tertiary hospital in Korea from 1 January 2012 to 31 December 2012. All
      adult patients who were diagnosed with febrile UTI and for whom data on blood and
      urine cultures were available were included in the study. Clinical examinations
      and laboratory tests were performed at the initial presentation. RESULTS: A total
      of the 325 patients with febrile UTI (median age: 60 years) were included for
      analysis, of whom 82 % were female. Bacteremia was detected in 106 of the 325
      patients (32.6 %), with Escherichia coli the most frequent pathogen detected
      (59.7 % of cases). Between the bacteremic and non-bacteremic groups, there was
      significant difference in age (67 vs. 57 years, respectively), flank pain (16 vs.
      7.8 %), suprapubic discomfort (0 vs. 4.6 %), body temperature (38.8 vs. 38.3 
      degrees C), respiratory rate (21 vs. 20/min), platelet count (170 vs. 186 *
      10(3)/MUL), C-reactive protein (10.2 vs. 8.3 mg/dL), and procalcitonin (1.5 vs.
      0.3 ng/mL) (P < 0.05 for all). In the multivariate logistic regression analysis,
      age [odds ratio (OR) 1.03; 95 % confidence interval (CI) 1.01-1.05], systolic
      blood pressure of <90 mmHg (OR 3.27; 95 % CI 1.13-9.45), body temperature of >39 
      degrees C (OR 4.26; 95 % CI 2.28-7.96), and procalcitonin level of >0.5 ng/dL (OR
      2.03; 95 % CI 1.07-3.86) were significantly associated with bacteremia.
      CONCLUSION: Among our adult patients with febrile UTI, age, systolic blood
      pressure, body temperature, and procalcitonin were significantly associated with
      bacteremia. We therefore suggest that these factors should be considered when
      deciding upon treatment options for febrile UTI patients at the ED.

PMID- 24677051
TI  - Astrocytes produce IL-19 in response to bacterial challenge and are sensitive to
      the immunosuppressive effects of this IL-10 family member.
AB  - There is growing appreciation that resident glial cells can initiate and/or
      regulate inflammation following trauma or infection in the central nervous system
      (CNS). We have previously demonstrated the ability of microglia and astrocytes to
      respond to bacterial pathogens or their products by rapid production of
      inflammatory mediators, followed by the production of the immunosuppressive
      cytokine interleukin (IL)-10. IL-19, another member of the IL-10 family of
      cytokines, has been studied in the context of a number of inflammatory conditions
      in the periphery and is known to modulate immune cell activity. In the present
      study, we demonstrate the constitutive and/or inducible expression of IL-19 and
      its cognate receptor subunits, IL-19Ralpha and IL-19Rbeta (also known as IL-20R1
      and IL-20R2, and IL-20RA and IL-20RB), in mouse brain tissue, and by primary
      murine and human astrocytes. We also provide evidence for the presence of a novel
      truncated IL-19Ralpha transcript variant in mouse brain tissue, but not glial
      cells, that shows reduced expression following bacterial infection. Importantly,
      IL-19R functionality in glia is indicated by the ability of IL-19 to regulate
      signaling component expression in these cells. Furthermore, while IL-19 itself
      had no effect on glial cytokine production, IL-19 treatment of bacterially
      infected or Toll-like receptor ligand stimulated astrocytes significantly
      attenuated pro-inflammatory cytokine production. The bacterially induced
      production of IL-19 by these resident CNS cells, the constitutive expression of
      its cognate receptor subunits, and the immunomodulatory effects of this cytokine,
      suggest a novel mechanism by which astrocytes can regulate CNS inflammation.

PMID- 24677053
TI  - Transphosphorylation of EGFR at Y845 plays an important role in its
      autophosphorylation and kinase activity.
AB  - Epidermal growth factor receptor (EGFR) plays a critical role in various types of
      human cancer such as lung, breast, brain and colon cancer. However, how EGFR
      activation is initiated and what type of interaction is linked to its
      transphosphorylation and autophosphorylation as well as the biological
      consequences in case of interruption and blockade of these two types of EGFR
      phosphorylation, remain elusive. In the present study, we provided evidence that
      EGFR transphosphorylation at Y845 indeed plays an important role in its
      autophosphorylation and kinase activity. Our results suggest that the modulation
      of EGFR transphosphorylation may influence its activity and function, indicating
      a potential target mechanism for treating EGFR-associated diseases and various
      types of cancer.

PMID- 24677055
TI  - cAMP Bastion, Afghanistan.

PMID- 24677056
TI  - Imaging in multiple sclerosis and related disorders.

PMID- 24677054
TI  - Probiotic L. reuteri treatment prevents bone loss in a menopausal ovariectomized
      mouse model.
AB  - Estrogen deficiency is a major risk factor for osteoporosis that is associated
      with bone inflammation and resorption. Half of women over the age of 50 will
      experience an osteoporosis related fracture in their lifetime, thus novel
      therapies are needed to combat post-menopausal bone loss. Recent studies suggest
      an important role for gut-bone signaling pathways and the microbiota in
      regulating bone health. Given that the bacterium Lactobacillus reuteri ATCC PTA
      6475 (L. reuteri) secretes beneficial immunomodulatory factors, we examined if
      this candidate probiotic could reduce bone loss associated with estrogen
      deficiency in an ovariectomized (Ovx) mouse menopausal model. Strikingly, L.
      reuteri treatment significantly protected Ovx mice from bone loss. Osteoclast
      bone resorption markers and activators (Trap5 and RANKL) as well as
      osteoclastogenesis are significantly decreased in L. reuteri-treated mice.
      Consistent with this, L. reuteri suppressed Ovx-induced increases in bone marrow
      CD4+ T-lymphocytes (which promote osteoclastogenesis) and directly suppressed
      osteoclastogenesis in vitro. We also identified that L. reuteri treatment
      modifies microbial communities in the Ovx mouse gut. Together, our studies
      demonstrate that L. reuteri treatment suppresses bone resorption and loss
      associated with estrogen deficiency. Thus, L. reuteri treatment may be a
      straightforward and cost-effective approach to reduce post-menopausal bone loss.

PMID- 24677057
TI  - Effect of adjuvant/neoadjuvant trastuzumab on clinical outcomes in patients with
      HER2-positive metastatic breast cancer.
AB  - BACKGROUND: The purpose of the current study was to describe the outcomes of
      patients with human epidermal growth factor receptor 2 (HER2)
      overexpressed/amplified (HER2+) early breast cancer who received adjuvant or
      neoadjuvant trastuzumab-based therapy and were subsequently retreated with
      trastuzumab for metastatic disease. METHODS: A total of 353 patients with
      metastatic HER2+ breast cancer who were treated with trastuzumab as part of their
      first-line treatment for metastatic disease were identified. A total of 75
      patients had received adjuvant or neoadjuvant trastuzumab-based therapy for early
      breast cancer, and 278 had not. Clinical outcomes of patients who had or had not
      received prior trastuzumab were compared using Cox proportional hazards
      regression and logistic regression analyses. Survival was estimated using the
      Kaplan-Meier method. RESULTS: The clinical benefit (complete response, partial
      response, or stable disease of >= 6 months) rates were 71% in the group who did
      not receive prior trastuzumab and 39% in the group previously treated with
      trastuzumab. The adjusted odds ratios were 0.28 (95% confidence interval [95%
      CI], 0.13-0.59; P = .0009) for clinical benefit rates and 0.39 (95% CI, 0.18
      0.82; P = .038) for objective (complete or partial) response rates. In the
      univariate analysis, the median overall survival rate was longer in the group who
      did not receive prior trastuzumab (36 months vs 28 months) (hazards ratio, 1.47;
      95% CI, 1.07-2.01 [P = .022]). The multivariate analysis found no significant
      difference in overall survival. CONCLUSIONS: When treated with trastuzumab for
      metastatic disease, patients with HER2+ breast cancer without prior exposure to
      trastuzumab were found to have superior clinical outcomes to those with prior
      exposure. Prior trastuzumab exposure should be considered in treatment algorithms
      and in HER2-targeted clinical trial enrollment for metastatic disease.

PMID- 24677058
TI  - 25th anniversary article: materials for high-performance biodegradable
      semiconductor devices.
AB  - We review recent progress in a class of silicon-based electronics that is capable
      of complete, controlled dissolution when immersed in water or bio-fluids. This
      type of technology, referred to in a broader sense as transient electronics, has
      potential applications in resorbable biomedical devices, eco-friendly
      electronics, environmental sensors, secure hardware systems and others. New
      results reported here include studies of the kinetics of hydrolysis of
      nanomembranes of single crystalline silicon in bio-fluids and aqueous solutions
      at various pH levels and temperatures. Evaluations of toxicity using live animal
      models and test coupons of transient electronic materials provide some evidence
      of their biocompatibility, thereby suggesting potential for use in bioresorbable
      electronic implants. 

PMID- 24677059
TI  - Evolving social health scheme for workers in unorganized sector: key evidences
      from study of cycle rickshaw pullers in Delhi, India.
AB  - BACKGROUND: In view of high out-of-pocket costs and low spending even for basic
      healthcare for the poor employed in the unorganized sector, policy makers in
      India have turned their attention to developing a financing mechanism for social
      health insurance with the desire to provide quality care to the poor and
      economically disadvantaged. OBJECTIVES: This study aims to assess and determine
      the disease profile, treatment expenditure and willingness to pay for health
      insurance among rickshaw pullers in Delhi. METHODS: The study was conducted among
      500 rickshaw pullers from five zones of the Municipal Corporation of Delhi,
      taking a sample of 100 from each zone. RESULTS: The average cost of treatment was
      Rs.505 for outpatient and Rs. 3200 for inpatient care. To finance the treatment
      expenditure, 27.5% of the respondents spent from their household savings, and 43%
      had to borrow funds. Any "spell of sickness" and "total expenditure on acute
      illness" were significantly (p < 0.01) associated with the willingness to pay for
      health insurance. Overall, the majority (83%) of participants were willing to pay
      for health insurance. CONCLUSION: The study provides the evidence for the need
      for urgent policy development by introducing a social health insurance package
      including wage losses for the vulnerable groups such as rickshaw pullers in the
      unorganized sector in India, which significantly contribute to pollution free and
      cheap transportation of community, tourists and commercial goods as well.

PMID- 24677060
TI  - Influence of the organic loading rate on the performance and the granular sludge
      characteristics of an EGSB reactor used for treating traditional Chinese medicine
      wastewater.
AB  - The effects of the organic loading rate (OLR) on the performance and the granular
      sludge characteristics of an expanded granular sludge bed (EGSB) reactor used for
      treating real traditional Chinese medicine (TCM) wastewater were investigated.
      Over 90% of the COD removal by the EGSB reactor was observed at the OLRs of 4 to
      13 kg COD/(m(3) day). However, increasing the OLR to 20 kg COD/(m(3) day) by
      reducing the hydraulic retention time (HRT 6 h) reduced the COD removal
      efficiency to 78%. The volatile fatty acid (VFA) concentration was 512.22 mg/L,
      resulting in an accumulation of VFAs, and propionic acid was the main
      acidification product, accounting for 66.51% of the total VFAs. When the OLR
      increased from 10 to 20 kg COD/(m(3) day), the average size of the granule sludge
      decreased from 469 to 258 MUm. There was an obvious reduction in the
      concentration of Ca(2+) and Mg(2+) in the granular sludge. The visible humic acid
      like peak was identified in the three-dimensional excitation-emission matrix
      (EEM) fluorescence spectra of the soluble microbial products (SMPs). The fatty
      acid bond, amide II bond, amide III bond, and C-H bond bending were also observed
      in the Fourier transform infrared (FTIR) spectra of the SMPs. Methanobacterium
      formicicum, Methanococcus, and Bacteria populations exhibited significant shifts,
      and these changes were accompanied by an increase in VFA production. The results
      indicated that a short HRT and high OLR in the EGSB reactor caused the
      accumulation of polysaccharides, protein, and VFAs, thereby inhibiting the
      activity of methanogenic bacteria and causing granular sludge corruption.

PMID- 24677061
TI  - Nanoscale zero-valent iron/AC as heterogeneous Fenton catalysts in three
      dimensional electrode system.
AB  - In the present work, nanoscale zero-valent iron/activated carbon (NZVI/AC) was
      investigated as heterogeneous Fenton catalyst in three-dimensional (3D) electrode
      system for methyl orange (MO) degradation. Some important operating parameters
      such as cathodic potential, pH, and O2 flow rate were investigated, exhibiting
      good decolorization. The mineralization of MO was significantly improved by 20
      35% compared to two-dimensional (2D) AC system at the optimum conditions.
      Although the TOC removal of AC was higher than NZVI/AC due to its good adsorption
      capacity initially, heterogeneous Fenton catalysis played a more and more
      important roles in the following test. After eight runs, NZVI/AC still exhibited
      excellent catalytic properties with low iron leaching. Further, a relatively
      comprehensive mechanism of NZVI/AC as particle electrodes in 3D system was
      proposed.

PMID- 24677062
TI  - Effects of phosphate and thiosulphate on arsenic accumulation in the species
      Brassica juncea.
AB  - Arsenic (As) is recognized as a toxic pollutant in soils of many countries. Since
      phosphorus (P) and sulphur (S) can influence arsenic mobility and
      bioavailability, as well as the plant tolerance to As, phytoremediation
      techniques employed to clean-up As-contaminated areas should consider the
      interaction between As and these two nutrients. In this study, the
      bioavailability and accumulation of arsenate in the species Brassica juncea were
      compared between soil system and hydroponics in relation to P and S concentration
      of the growth substrate. In one case, plants were grown in pots filled with soil
      containing 878 mg As kg(-1). The addition of P to soil resulted in increased As
      desorption and significantly higher As accumulation in plants, with no effect on
      growth. The absence of toxic effects on plants was likely due to high S in soil,
      which could efficiently mitigate metal toxicity. In the hydroponic experiment,
      plants were grown with different combinations of As (0 or 100 MUM) and P (56 or
      112 MUM). S at 400 MUM was also added to the nutrient solution of control (-As)
      and As-treated plants, either individually or in combination with P. The addition
      of P reduced As uptake by plants, while high S resulted in higher As accumulation
      and lower P content. These results suggest that S can influence the interaction
      between P and As for the uptake by plants. The combined increase of P and S in
      the nutrient solution did not lead to higher accumulation of As, but enhanced As
      translocation from the root to the shoot. This aspect is of relevance for the
      phytoremediation of As-contaminated sites.

PMID- 24677065
TI  - Generation of an attenuated Tiantan vaccinia virus by deletion of the
      ribonucleotide reductase large subunit.
AB  - Attenuation of the virulence of vaccinia Tiantan virus (VTT) underlies the
      strategy adopted for mass vaccination campaigns. This strategy provides
      advantages of safety and efficacy over traditional vaccines and is aimed at
      minimization of adverse health effects. In this study, a mutant form of the
      virus, MVTT was derived from VTT by deletion of the ribonucleotide reductase
      large subunit (R1) (TI4L). Compared to wild-type parental (VTT) and revertant
      (VTT-rev) viruses, virulence of the mutant MVTT was reduced by 100-fold based on
      body weight reduction and by 3,200-fold based on determination of the
      intracranial 50% lethal infectious dose. However, the immunogenicity of MVTT was
      equivalent to that of the parental VTT. We also demonstrated that the TI4L gene
      is not required for efficient replication. These data support the conclusion that
      MVTT can be used as a replicating virus vector or as a platform for the
      development of vaccines against infectious diseases and for cancer therapy.

PMID- 24677066
TI  - Diagnosis of closed injury and neoplasm of the brachial plexus by
      ultrasonography.
AB  - PURPOSE: To evaluate the feasibility and accuracy of high-frequency sonography
      (US) in diagnosing traumatic brachial plexus (BP) lesions and neoplasms in the
      adult. METHODS: Eleven patients with suspected BP closed trauma, 6 patients with
      BP neoplasm, and 12 healthy volunteers were scanned. The US findings were
      compared with surgical findings. RESULTS: The interscalene space and
      intervertebral foramina were useful anatomic markers in identifying the BP. In
      the 24 sites examined in the normal group (12 subjects examined on both sides),
      the fifth to seventh cervical nerve roots (C5-7, including upper and middle
      trunk) were seen, whereas the eighth cervical and first thoracic nerve roots (C8,
      T1, including the lower trunk) were seen in 91.7% (22/24) of the subjects. The BP
      appeared as three or four discrete rounded hypoechoic nodules between the
      anterior scalene and middle scalene muscle in transverse views at the C5-7 level,
      representing the trunks in the sagittal oblique section. In the BP trauma group
      (n = 11), the normal nerve trunk was interrupted, and lesions were shown as
      thickening and swelling with indistinct inner structures. In the neoplasm group
      (n = 6), masses were shown as hypoechoic masses. CONCLUSIONS: High-frequency US
      is valuable in diagnosing BP closed injuries and neoplasms.

PMID- 24677067
TI  - Galleria mellonella as an alternative model of Coxiella burnetii infection.
AB  - Coxiella burnetii is a Gram-negative intracellular bacterium and is the causative
      agent of the zoonotic disease Q fever. Several rodent and non-human primate
      models of virulent phase I C. burnetii [Nine Mile (NM)I] have been developed, and
      have been used to determine the efficacy of antibiotics and vaccine candidates.
      However, there are several advantages to using insect models to study host
      microbe interactions, such as reduced animal use, lowered cost and ease of
      manipulation in high containment. In addition, many laboratories use the
      avirulent phase II C. burnetii clone (NMII) to study cellular interactions and
      identify novel virulence determinants using genetic manipulation. We report that
      larvae of the greater wax moth, Galleria mellonella, were susceptible to
      infection with both C. burnetii NMI and NMII. Following subcutaneous infection,
      we report that intracellular bacteria were present within haemocytes and that
      larval death occurred in a dose-dependent manner. Additionally, we have used the
      model to characterize the role of the type 4 secretion system in C. burnetii NMII
      and to determine antibiotic efficacy in a non-mammalian model of disease. 

PMID- 24677069
TI  - Interaction between nonviral reprogrammed fibroblast stem cells and trophic
      factors for brain repair.
AB  - There are currently no known treatment options that actually halt or permanently
      reverse the pathology evident in any neurodegenerative condition. Arguably, one
      of the most promising avenues for creating viable neuronal treatments could
      involve the combined use of cell replacement and gene therapy. Given the
      complexity of the neurodegenerative process, it stands to reason that adequate
      therapy should involve not only the replacement of loss neurons/synapses but also
      the interruption of multiple pro-death pathways. Thus, we propose the use of stem
      cells that are tailored to express specific trophic factors, thereby potentially
      encouraging synergistic effects between the stem cell properties and those of the
      trophic factors. The trophic factors, brain-derived neurotropic factor (BDNF),
      glial cell-derived neurotropic factor (GDNF), fibroblast growth factor (FGF) 2,
      and insulin-like growth factor (IGF) 1, in particular, have demonstrated
      neuroprotective actions in a number of animal models. Importantly, we use a
      nonviral approach, thereby minimizing the potential risk for DNA integration and
      tumor formation. The present study involved the development of a nonviral
      reprogramming system to transform adult mature mouse fibroblasts into progressive
      stages of cell development. We also tailored these stem cells to individually
      express each of the trophic factors, including BDNF, GDNF, FGF2, and IGF1.
      Significantly, central infusion of BDNF-expressing stem cells prevented the in
      vivo loss of neurons associated with infusion of the endotoxin,
      lipopolysaccharide (LPS). This is particularly important in light of the role of
      inflammatory processes that are posited to play in virtually all
      neurodegenerative states. Hence, the present results support the utility of using
      combined gene and cell-targeting approaches for neuronal pathology. 

PMID- 24677070
TI  - Do empathy, perspective-taking, sense of power and personality differ across
      undergraduate education and are they inter-related?
AB  - Empathy is desirable in all health care professionals in their interactions with
      patients and each other. Empathy in its cognitive (perspective-taking) and
      affective forms has been well-studied in the literature and in fact, is shown in
      most studies to decline during undergraduate and graduate medical education.
      Empathy has also been shown to be inversely proportional to one's sense of power
      (SOP) in the business literature. In addition, the relationship of empathy to
      personality traits has not been examined. This cross-sectional study of four
      cohorts of undergraduate medical students at a private mid-Atlantic medical
      school compares the empathy of first, second, third and fourth year medical
      students to see if there is a decline across the medical school experience. It
      also examines the relationship among empathy, SOP and personality type across the
      4 years of medical school. Unlike in many previous studies, we found no decline
      in student empathy. We found no significant relationship between SOP and empathy.
      Finally, there were no significant differences in power perception and
      personality measures across all educational years surveyed. 

PMID- 24677068
TI  - Regulation of membrane excitability: a convergence on voltage-gated sodium
      conductance.
AB  - The voltage-gated sodium channel (Nav) plays a key role in regulation of neuronal
      excitability. Aberrant regulation of Nav expression and/or function can result in
      an imbalance in neuronal activity which can progress to epilepsy. Regulation of
      Nav activity is achieved by coordination of a multitude of mechanisms including
      RNA alternative splicing and translational repression. Understanding of these
      regulatory mechanisms is complicated by extensive genetic redundancy: the
      mammalian genome encodes ten Navs. By contrast, the genome of the fruitfly,
      Drosophila melanogaster, contains just one Nav homologue, encoded by paralytic
      (DmNa v ). Analysis of splicing in DmNa v shows variants exhibit distinct gating
      properties including varying magnitudes of persistent sodium current (INaP).
      Splicing by Pasilla, an identified RNA splicing factor, alters INaP magnitude as
      part of an activity-dependent mechanism. Enhanced INaP promotes membrane
      hyperexcitability that is associated with seizure-like behaviour in Drosophila.
      Nova-2, a mammalian Pasilla homologue, has also been linked to splicing of Navs
      and, moreover, mouse gene knockouts display seizure-like behaviour.Expression
      level of Navs is also regulated through a mechanism of translational repression
      in both flies and mammals. The translational repressor Pumilio (Pum) can bind to
      Na v transcripts and repress the normal process of translation, thus regulating
      sodium current (INa) density in neurons. Pum2-deficient mice exhibit spontaneous
      EEG abnormalities. Taken together, aberrant regulation of Nav function and/or
      expression is often epileptogenic. As such, a better understanding of regulation
      of membrane excitability through RNA alternative splicing and translational
      repression of Navs should provide new leads to treat epilepsy.

PMID- 24677076
TI  - Dynamics of soil diazotrophic community structure, diversity, and functioning
      during the cropping period of cotton (Gossypium hirsutum).
AB  - The soil sampled at different growth stages along the cropping period of cotton
      were analyzed using various molecular tools: restriction fragment length
      polymorphism (RFLP), terminal restriction length polymorphism (T-RFLP), and
      cloning-sequencing. The cluster analysis of the diazotrophic community structure
      of early sampled soil (0, 15, and 30 days) was found to be more closely related
      to each other than the later sampled one. Phylogenetic and diversity analysis of
      sequences obtained from the first (0 Day; C0) and last soil sample (180 day;
      C180) confirmed the data. The phylogenetic analysis revealed that C0 was having
      more unique sequences than C180 (presence of gamma-Proteobacteria exclusively in
      C0). A relatively higher richness of diazotrophic community sequences was
      observed in C0 (S(ACE) : 30.76; S(Chao1) : 20.94) than C180 (S(ACE) : 18.00;
      S(Chao1) : 18.00) while the evenness component of Shannon diversity index
      increased from C0 (0.97) to C180 (1.15). The impact of routine agricultural
      activities was more evident based on diazotrophic activity (measured by acetylene
      reduction assay) than its structure and diversity. The nitrogenase activity of C0
      (1264.85 +/- 35.7 etamol of ethylene production g(-1) dry soil h(-1) ) was
      statistically higher when compared to all other values (p < 0.05). There was no
      correlation found between diazotrophic community structure/diversity and N2
      fixation rates. Thus, considerable functional redundancy of nifH was concluded to
      be existing at the experimental site.

PMID- 24677077
TI  - Cardiac titin, the giant sarcomeric protein in health and disease.

PMID- 24677078
TI  - [Infective endocarditis in patient post transcatheter aortic valve replacement -
      is conservative treatment possible?].

PMID- 24677079
TI  - Implantation of a bioabsorbable vascular scaffold into a coronary vein graft: a
      two-week angiography follow-up.

PMID- 24677080
TI  - Successful thrombolytic treatment of right sided massive intracardiac thrombus
      and pulmonary embolism.

PMID- 24677081
TI  - Visceral arteries thrombosis as a fatal complication of intraaortic balloon
      malposition.

PMID- 24677082
TI  - Spaghetti-like leads in the heart - a complication of permanent heart
      stimulation.

PMID- 24677083
TI  - Magnetically responsive microflaps reveal cell membrane boundaries from multiple
      angles.
AB  - A microflap system to incline adherent cells in the desired orientation is
      described. Inclination angles of cell-laden microflaps are precisely controlled
      by the applied magnetic field, enabling us to observe cell-membrane boundaries
      from multiple angles. This system is equipped with conventional microscopes,
      allowing clear focused images of cell-membrane boundaries to be obtained with
      high magnification. 

PMID- 24677084
TI  - Introduction to "defense mechanisms in psychotherapy".

PMID- 24677088
TI  - Molecular cytogenetic study of the European bitterling Rhodeus amarus (Teleostei:
      Cyprinidae: Acheilognathinae).
AB  - The European bitterlings (Rhodeus amarus) from the Eastern locations were
      cytogenetically examined by conventional and molecular techniques. All analyzed
      individuals presented invariably the same chromosomal constitution of 2n = 48,
      with 8 metacentrics + 20 submetacentrics + 20 subtelo-acrocentrics and C-banding
      positive heterochromatin at the pericentromeric regions in most of the
      chromosomes. Moreover, some of the chromosomes had short arms entirely built with
      heterochromatin. GC-rich Ag-NORs (nucleolus organizer regions) were located at
      the short arms of two submetacentric chromosomes, and the length polymorphism of
      these regions was found. Multiple location of 28S rDNA sequences with
      fluorescence in situ hybridization signals was observed on the long and/or short
      arms of three submetacentric chromosomes including NOR regions and short arms of
      three to five acrocentric chromosomes in the studied fish. 5S rDNA sites were
      found on the short arms of two subtelocentric chromosomes, and telomeric repeats
      were localized at the ends of all chromosomes. Provided results have expanded our
      knowledge concerning genetic characteristics of the European bitterlings that may
      be profitable in the conservation programs of this endangered species.

PMID- 24677091
TI  - Controlling SEI formation on SnSb-porous carbon nanofibers for improved Na ion
      storage.
AB  - Porous carbon nanofiber (CNF)-supported tin-antimony (SnSb) alloys are
      synthesized and applied as a sodium-ion battery anode. The chemistry and
      morphology of the solid electrolyte interphase (SEI) film and its correlation
      with the electrode performance are studied. The addition of fluoroethylene
      carbonate (FEC) in the electrolyte significantly reduces electrolyte
      decomposition and creates a very thin and uniform SEI layer on the cycled
      electrode surface, which an promote the kinetics of Na-ion
      migration/transportation, leading to excellent electrochemical performance. 

PMID- 24677090
TI  - Polysaccharide from Inonotus obliquus inhibits migration and invasion in B16-F10
      cells by suppressing MMP-2 and MMP-9 via downregulation of NF-kappaB signaling
      pathway.
AB  - Polysaccharides derived from Inonotus obliquus (PIO) are known to possess
      multiple pharmacological activities including antitumor activity. However, the
      possible molecular mechanisms of these activities are unknown. In the present
      study, we determined the anti-metastatic potential and signaling pathways of PIO
      in the highly metastatic B16-F10 mouse melanoma cell line in vitro. We found that
      PIO suppressed the migration and invasive ability of B16-F10 cells and decreased
      the expression levels and activities of matrix metalloproteinase (MMP)-2 and MMP
      9. In addition, PIO decreased the phosphorylation levels of extracellular signal
      regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen
      activated protein kinase (MAPK); PIO also decreased the expression level of
      cyclooxygenase (COX)-2 and inhibited the nuclear translocation of nuclear factor
      kappaB (NF-kappaB) in B16-F10 melanoma cells. These results suggest that PIO
      could suppress the invasion and migration of B16-F10 melanoma cells by reducing
      the expression levels and activities of MMP-2 and MMP-9 through suppressing MAPK,
      COX-2 and NF-kappaB signaling pathways.

PMID- 24677089
TI  - High-frequency vaccine-induced CD8+ T cells specific for an epitope naturally
      processed during infection with Mycobacterium tuberculosis do not confer
      protection.
AB  - Relatively few MHC class I epitopes have been identified from Mycobacterium
      tuberculosis, but during the late stage of infection, CD8(+) T-cell responses to
      these epitopes are often primed at an extraordinary high frequency. Although
      clearly available for recognition during infection, their role in resistance to
      mycobacterial infections still remain unclear. As an alternative to DNA and viral
      vaccination platforms, we have exploited a novel CD8(+) T-cell-inducing adjuvant,
      cationic adjuvant formulation 05 (dimethyldioctadecylammonium/trehalose
      dibehenate/poly (inositic:cytidylic) acid), to prime high-frequency CD8 responses
      to the immunodominant H2-K(b) -restricted IMYNYPAM epitope contained in the
      vaccine Ag tuberculosis (TB)10.4/Rv0288/ESX-H (where ESX is mycobacterial type
      VII secretion system). We report that the amino acid C-terminal to this minimal
      epitope plays a decisive role in proteasomal cleavage and epitope priming. The
      primary structure of TB10.4 is suboptimal for proteasomal processing of the
      epitope and amino acid substitutions in the flanking region markedly increased
      epitope-specific CD8(+) T-cell responses. One of the optimized sequences was
      contained in the closely related TB10.3/Rv3019c/ESX-R Ag and when recombinantly
      expressed and administered in the cationic adjuvant formulation 05 adjuvant, this
      Ag promoted very high CD8(+) T-cell responses. This abundant T-cell response was
      functionally active but provided no protection against challenge, suggesting that
      CD8(+) T cells play a limited role in protection against M. tuberculosis in the
      mouse model. 

PMID- 24677093
TI  - Role of AMP-activated protein kinase in cancer therapy.
AB  - Recent advances in AMP-activated protein kinase (AMPK) as a target in cancer
      waxed and waned over the past decade of cancer research. AMPK is a cellular
      energy sensor, present in almost all eukaryotic cells. An elevated AMP/ATP ratio
      activates the AMPK, which in turn inhibits energy-consuming processes and induces
      catabolic events that generate ATP to restore the energy homeostasis inside the
      cell. Several reports have indicated that AMPK regulates several metabolic
      pathways and may be a potential therapeutic target for the treatment of cancer.
      Cancer cells have specific metabolic changes that differ from normal cells, and
      AMPK prevents the deregulated processes in cancer. AMPK may also act to inhibit
      tumor formation through modulation of cell growth, cell proliferation, autophagy,
      stress responses, and cell polarity. AMPK has been shown to inhibit mammalian
      target of rapamycin (mTOR) through tuberous sclerosis complex 2 (TSC2)
      phosphorylation and phosphatase and tensin homolog (PTEN), considered as central
      cell growth controller signals in diseases. In response to glucose deprivation,
      AMPK phosphorylates and activates p53, which induces cell cycle arrest in the
      G1/S phase of the cell cycle. AMPK has also been reported to block cyclin
      dependent kinases through phosphorylation of p27(kip1) , promoting its
      stabilization and allowing cells to survive metabolic stress via induction of
      autophagy. Additionally, AMPK induces autophagy by phosphorylation and activation
      of eEF-2 kinase, and prevents the formation of new proteins. AMPK activators are
      also used for the treatment of type II diabetes and cancer. This review focuses
      on AMPK activation and its possible therapeutic role in the treatment of cancer.

PMID- 24677092
TI  - Interleukin-1 beta enhances endocytosis of glial glutamate transporters in the
      spinal dorsal horn through activating protein kinase C.
AB  - Excessive activation of glutamate receptors in spinal dorsal horn neurons is a
      key mechanism leading to abnormal neuronal activation in pathological pain
      conditions. Previous studies have shown that activation of glutamate receptors in
      the spinal dorsal horn is enhanced by impaired glial glutamate transporter
      functions and proinflammatory cytokines including interleukin-1 beta (IL-1beta).
      In this study, we for the first time revealed that spinal glial glutamate
      transporter activities in the neuropathic animals are attenuated by endogenous IL
      1beta. Specifically, we demonstrated that nerve injury results in an increased
      expression of IL-1beta and activation of PKC in the spinal dorsal horn as well as
      suppression of glial glutamate uptake activities. We provided evidence that the
      nerve-injury induced suppression of glial glutamate uptake is at least in part
      ascribed to endogenous IL-1beta and activation of PKC in the spinal dorsal horn.
      IL-1beta reduces glial glutamate transporter activities through enhancing the
      endocytosis of both GLT-1 and GLAST glial glutamate transporters. The IL-1beta
      induced trafficking of glial glutamate transporters is through the calcium/PKC
      signaling pathway, and the dynamin-dependent endocytosis, which is dependent on
      the integrity of actin filaments. The signaling pathway regulating glial
      glutamate transporters revealed in this study provides novel targets to attenuate
      aberrant activation of glutamate receptors in the spinal dorsal horn, which could
      ultimately help the development of analgesics.

PMID- 24677095
TI  - Pharmacological evaluation of the efficacy of Dysoxylum binectariferum stem bark
      and its active constituent rohitukine in regulation of dyslipidemia in rats.
AB  - The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum
      stem bark and its major active constituent rohitukine was evaluated in a high fat
      diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200
      mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay
      guided fractionation of ethanolic extract resulted in the identification of known
      alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg)
      significantly decreased the plasma levels of total cholesterol (24 %),
      phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %)
      and low density lipoprotein (32 %) accompanied with an increase in high density
      lipoprotein (21 %). The present study demonstrated that ethanolic extract of
      Dysoxylum binectariferum stem bark and its major constituent rohitukine both have
      antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity
      of rohitukine can be correlated to its effect on enzymes involved in lipid
      metabolism.

PMID- 24677094
TI  - CD99 drives terminal differentiation of osteosarcoma cells by acting as a spatial
      regulator of ERK 1/2.
AB  - Differentiation therapy is an attractive treatment for osteosarcoma (OS). CD99 is
      a cell surface molecule expressed in mesenchymal stem cells and osteoblasts that
      is maintained during osteoblast differentiation while lost in OS. Herein, we show
      that whenever OS cells regain CD99, they become prone to reactivate the terminal
      differentiation program. In differentiating conditions, CD99-transfected OS cells
      express osteocyte markers, halt proliferation, and largely die by apoptosis,
      resembling the fate of mature osteoblasts. CD99 induces ERK activation,
      increasing its membrane-bound/cytoplasmic form rather than affecting its nuclear
      localization. Through cytoplasmic ERK, CD99 promotes activity of the main
      osteogenic transcriptional factors AP1 and RUNX2, which in turn enhance
      osteocalcin and p21(WAF1/CIP1) , leading to G0 /G1 arrest. These data underscore
      the alternative positions of active ERK into distinct subcellular compartments as
      key events for determining OS fate.

PMID- 24677096
TI  - Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety
      evaluation in mice.
AB  - The analgesic activity of Porcellio laevis Latreille, Rhizoma Corydalis, and
      Radix Cynanchi Paniculati have been reported in recent years. A new formula named
      Jia-Yuan-Qing pill (JYQP) is therefore created by combining the three herbs at
      9:7:7 ratio according to traditional Chinese theories. The present study aims to
      evaluate the effect of JYQP as a novel painkiller in various models. Acute
      toxicity test was applied to evaluate the safety of JYQP. Acetic-acid-induced
      writhing, hot plate test, formalin test, and naloxone-pretreated writhing test
      were employed to elaborate the analgesic activity of JYQP and its possible
      mechanism. A bone cancer pain mouse model was performed to further assess the
      effect of JYQP in relieving cancer pain. Test on naloxone-precipitated withdrawal
      symptoms was conduct to examine the physical dependence of mice on JYQP. Data
      revealed that JYQP reduced writhing and stretching induced by acetic acid;
      however, this effect could not be blocked by naloxone. JYQP specifically
      suppressed the phase II reaction time in formalin-treated mice; meanwhile, no
      analgesic effect of JYQP in hot plate test was observed, indicating that JYQP
      exerts analgesic activity against inflammatory pain rather than neurogenic pain.
      Furthermore, JYQP could successfully relieve bone cancer pain in mice. No
      physical dependence could be observed upon long-term administration in mice.
      Collectively, our present results provide experimental evidence in supporting
      clinical use of JYQP as an effective and safe agent for pain treatment. 

PMID- 24677097
TI  - Improved sanguinarine production via biotic and abiotic elicitations and
      precursor feeding in cell suspensions of latex-less variety of Papaver somniferum
      with their gene expression studies and upscaling in bioreactor.
AB  - Elicitors play an important role in challenging the plant defense system through
      plant-environment interaction and thus altering the secondary metabolite
      production. Culture filtrates of four endophytic fungi, namely, Chaetomium
      globosum, Aspergillus niveoglaucus, Paecilomyces lilacinus, and Trichoderma
      harzianum were tested on embryogenic cell suspensions of latex-less Papaver
      somniferum in dose-dependent kinetics. Besides this, abiotic elicitors salicylic
      acid, hydrogen peroxide, and carbon dioxide were also applied for improved
      sanguinarine production. Maximum biomass accumulation (growth index (GI) = 293.50
      +/- 14.82) and sanguinarine production (0.090 +/- 0.008 % dry wt.) were
      registered by addition of 3.3 % v/v T. harzanium culture filtrate. Interestingly,
      it was further enhanced (GI = 323.40 +/- 25.30; 0.105 +/- 0.008 % dry wt.) when
      T. harzanium culture filtrate was employed along with 50 MUM shikimate. This was
      also supported by real-time (RT) (qPCR), where 8-9-fold increase in
      cheilanthifoline synthase (CFS), stylopine synthase (STS),
      tetrahydroprotoberberine cis-N-methyltransferase (TNMT), and protopine 6
      hydroxylase (P6H) transcripts was observed. Among abiotic elicitors, while
      hydrogen peroxide and carbon dioxide registered low level of sanguinarine
      accumulation, maximum sanguinarine content was detected by 250 MUM salicylic acid
      (0.058 +/- 0.003 % dry wt.; GI = 172.75 +/- 13.40). RT (qPCR) also confirms the
      downregulation of sanguinarine pathway on CO2 supplementation. Various parameters
      ranging from agitation speed (70 rpm), impeller type (marine), media volume (2
      l), inoculum weight (100 g), and culture duration (9 days) were optimized during
      upscaling in 5-l stirred tank bioreactor to obtain maximum sanguinarine
      production (GI = 434.00; 0.119 +/- 0.070 % dry wt.). Addition of 3.3 % v/v T.
      harzanium culture filtrate and 50-MUM shikimate was done on the 6th day of
      bioreactor run.

PMID- 24677099
TI  - An inability to exclude visual noise in migraine.
AB  - PURPOSE: People with migraine are relatively poor at judging the direction of
      motion of coherently moving signal dots when interspersed with noise dots
      drifting in random directions, a task known as motion coherence. Although this
      has been taken as evidence of impoverished global pooling of motion signals, it
      could also arise from unreliable coding of local direction (of each dot), or an
      inability to segment signal from noise (noise-exclusion). The aim of this study
      was to determine how these putative limits contribute to impoverished motion
      processing in migraine. METHODS: Twenty-two participants with migraine (mean age,
      34.7 +/- 8.3 years; 16 female) and 22 age- and sex-matched controls (mean age,
      34.4 +/- 6.2 years) performed a motion-coherence task and a motion-equivalent
      noise task, the latter quantifying local and global limits on motion processing.
      In addition, participants were tested on analogous equivalent noise paradigms
      involving judgments of orientation and size, so that the specificity of any
      findings (to visual dimension) could be ascertained. RESULTS: Participants with
      migraine exhibited higher motion-coherence thresholds than controls (P = 0.01,
      independent t-test). However, this difference could not be attributed to deficits
      in either local or global processing since they performed normally on all
      equivalent noise tasks (P > 0.05, multivariate ANOVA). CONCLUSIONS: These
      findings indicate that motion perception in the participants with migraine was
      limited by an inability to exclude visual noise. We suggest that this is a
      defining characteristic of visual dysfunction in migraine, a theory that has the
      potential to integrate a wide range of findings in the literature.

PMID- 24677100
TI  - Diclofenac protects cultured human corneal epithelial cells against
      hyperosmolarity and ameliorates corneal surface damage in a rat model of dry eye.
AB  - PURPOSE: Dry eye syndrome (DES) is characterized by an increase in tear
      osmolarity and induction of the expression and nuclear localization of an
      osmoprotective transcription factor (nuclear factor of activated T-cells 5
      [NFAT5]) that plays an important role in providing protection against
      hyperosmotic tears. In this study, we screened medicines already in clinical use
      with a view of finding compounds that protect cultured human corneal epithelial
      cells against hyperosmolarity-induced cell damage. METHODS: Viable cell number
      was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) method and cellular NFAT5 level was measured by immunoblotting. The
      rat model for DES was developed by removal of the lacrimal glands, with an
      assessment of corneal surface damage based on levels of fluorescein staining and
      epithelial apoptosis. RESULTS: Some nonsteroidal anti-inflammatory drugs
      (NSAIDs), including diclofenac sodium (diclofenac), were identified during the
      screening procedure. These NSAIDs were able to suppress hyperosmolarity-induced
      apoptosis and cell growth arrest. In contrast, other NSAIDs, including bromfenac
      sodium (bromfenac), did not exert such a protective action. Treatment of cells
      with diclofenac, but not bromfenac, stimulated both the nuclear localization and
      expression of NFAT5 under hyperosmotic conditions. In the rat model for DES,
      topical administration of diclofenac (but not bromfenac) to eyes reduced corneal
      surface damage without affecting the volume of tear fluid. CONCLUSIONS:
      Diclofenac appears to protect cells against hyperosmolarity-induced cell damage
      and NFAT5 would play an important role in this protective action. The findings
      reported here may also indicate that the topical administration of diclofenac to
      eyes may be therapeutically beneficial for DES patients.

PMID- 24677101
TI  - Contribution of shape and gradient refractive index to the spherical aberration
      of isolated human lenses.
AB  - PURPOSE: To estimate the contribution of 3-dimensional (3D) lens geometry and
      gradient refractive index (GRIN) to the lens spherical aberration (SA) with age.
      METHODS: A total of 35 donor human lenses (19-71 years) were imaged with 3D
      spectral optical coherence tomography (sOCT). Paraxial and nonparaxial back focal
      length were measured with laser ray tracing (LRT). The parameters of a 4-variable
      3D GRIN model were reconstructed from the data using a global search algorithm.
      Spherical aberration was calculated for GRIN lenses and their corresponding
      homogeneous lenses. RESULTS: Lens thickness and radii of curvature increased
      significantly with age. Negative anterior conic constant shifted toward more
      positive values (slope: 0.228, P < 0.001), whereas posterior values remained
      almost constant (slope: 0.0275, P = 0.002). We found a minor decrease and a small
      significant increase of nucleus and surface refractive index, respectively. The
      GRIN meridional power exponent had a tendency to increase, indicating a
      flattening of GRIN distribution, whereas the axial exponent remained almost
      constant. We did not find a significant age-dependence of the equivalent index.
      The back focal length had a significant increase with age (P < 0.001). The SA
      shifted toward less-negative values (slope: 0.0249, P < 0.001) at higher rates
      when considering the reconstructed GRIN (slope: 0.041, P < 0.001). CONCLUSIONS:
      Three-dimensional sOCT and LRT allowed reconstruction of lens geometry and GRIN
      in isolated lenses. The constancy of the GRIN axial power exponent, and the
      opposite slopes of surface and nucleus indices with age, explain the minor
      variations of the average index. Both geometrical changes and increase in the
      GRIN meridional power exponent contribute to the age-dependent shift of negative
      SA.

PMID- 24677098
TI  - Quo vadis plant hormone analysis?
AB  - Plant hormones act as chemical messengers in the regulation of myriads of
      physiological processes that occur in plants. To date, nine groups of plant
      hormones have been identified and more will probably be discovered. Furthermore,
      members of each group may participate in the regulation of physiological
      responses in planta both alone and in concert with members of either the same
      group or other groups. The ideal way to study biochemical processes involving
      these signalling molecules is 'hormone profiling', i.e. quantification of not
      only the hormones themselves, but also their biosynthetic precursors and
      metabolites in plant tissues. However, this is highly challenging since trace
      amounts of all of these substances are present in highly complex plant matrices.
      Here, we review advances, current trends and future perspectives in the analysis
      of all currently known plant hormones and the associated problems of extracting
      them from plant tissues and separating them from the numerous potentially
      interfering compounds. 

PMID- 24677102
TI  - Changes in choroidal thickness after trabeculectomy in primary angle closure
      glaucoma.
AB  - PURPOSE: The purpose of this study was to evaluate changes in choroidal thickness
      (CT) in advanced or late-stage primary angle closure glaucoma (PACG) patients who
      had undergone trabeculectomy. METHODS: This study included 23 eyes with PACG that
      required trabeculectomy. Enhanced depth imaging optical coherence tomography was
      used to measure CT before and 7 days after trabeculectomy. The relationships
      between changes in CT and changes in IOP and axial length were explored. RESULTS:
      At all nine macular locations, CT was significantly higher after trabeculectomy,
      with the exception of two sites. CT at locations close to the macula exhibited a
      greater increase after surgery (except for the inferior location), although there
      were no significant differences compared to locations farther from the macula.
      The mean CTs (+/- SD) under the fovea before and after the surgery were 282.3 (+/
      42.4) MUm and 311.6 (+/- 59.9) MUm, respectively. The mean IOP (+/- SD)
      decreased from 25.9 (+/- 11.0) mm Hg to 11.8 (+/- 3.2) mm Hg (without
      antiglaucoma medications), which positively related to the shortened axial length
      after surgery (P = 0.019). However, the changes in CT were not correlated with
      either IOP or axial length. CONCLUSIONS: Short-term CT increased following
      trabeculectomy in PACG, but it was not related to decreased IOP or shortened
      axial length. The potential role for and significance of CT increase after
      trabeculectomy remains to be interpreted.

PMID- 24677103
TI  - Autocrine impact of VEGF-A on uveal melanoma cells.
AB  - PURPOSE: Tumor-derived VEGF-A, apart from expediting sufficient vascularization,
      subsequent tumor growth, and metastatic spread, can act on malignant cells
      themselves provided that VEGF receptors 1 or 2 (VEGF-R1, -R2) are co-expressed.
      The study goal was to investigate whether such autocrine VEGF-A signaling exists
      in uveal melanoma (UM). METHODS: Primary (MEL-270, OM-431) and metastatic (OMM
      2.3, OMM-2.5) UM cell lines were analyzed for VEGF-A, VEGF-R1, and VEGF-R2
      expression by RT-PCR, ELISA (VEGF-A protein), and immunocytochemistry (VEGF
      receptors). Proliferation of UM cells incubated with neutralizing anti-VEGF-A
      antibody bevacizumab (<= 2.5 mg/mL), or VEGF-A (<= 100 ng/mL) was assessed by
      bromodeoxyuridine (BrdU) ELISA. It was measured by real-time PCR, whether VEGF-A
      (100 ng/mL) modulated the expression ratio of VEGF-A itself and its
      antiangiogenic antagonist pigment epithelium-derived factor (PEDF). RESULTS: All
      UM cells expressed VEGF-A, VEGF-R1, VEGF-R2 mRNA, and protein. In each cell line,
      the proliferation was stimulated by VEGF-A or inhibited by blocking VEGF-A, or
      both: bevacizumab significantly decreased the proliferation in MEL-270 (P =
      0.005), OMM-2.3 (P = 0.001), and OMM-2.5 (P = 0.011). Increased VEGF-A signaling
      significantly raised the proliferation in MEL-270, OM-431 (P < 0.001,
      respectively), and OMM-2.3 (P = 0.043) in a dose-dependent manner but did not
      significantly change the VEGF-A/PEDF mRNA expression ratio. CONCLUSIONS:
      Autocrine VEGF-A signaling seems to be present in UM, sustaining the
      proliferation of both primary and metastatic UM cells. Apparently, VEGF-A
      signaling in UM cells neither acts retroactively on VEGF-A expression, in the
      sense of a feedback loop, nor contributes to a pro-angiogenic shift of the VEGF
      A/PEDF ratio.

PMID- 24677104
TI  - Cytokine deposition alters leukocyte morphology and initial recruitment of
      monocytes and gammadeltaT cells after corneal injury.
AB  - PURPOSE: An in vivo mouse model reproducibly induces recurrent epithelial
      erosions in wild-type mice spontaneously 2 weeks after a single 1.5-mm corneal
      debridement wound made with a dulled blade. When 1.5-mm wounds are made by a
      rotating burr so that the corneal epithelial basement membrane is removed,
      corneas heal without developing erosions. Here, we characterize differences in
      cytokine deposition and changes in leukocytes between 0 and 6 hours after dulled
      blade and rotating-burr wounding. METHODS: BALB/c mice were used to study 1.5-mm
      corneal wounds made using a dulled blade or a rotating burr. Mice were studied
      immediately after wounding (0 hour) and at 6 hours in vivo and in vitro in organ
      culture. Corneas, corneal extracts, and collagenase digests from naive and
      wounded mice were used for three-dimensional (3D) confocal imaging, cytokine
      arrays, and flow cytometry. RESULTS: Confocal imaging showed CD45, a protein
      derived from leukocytes, accumulates at the wound edge by 3 and 6 hours after
      wounding in vivo but not in vitro with more CD45 accumulating after dulled-blade
      compared with rotating-burr wounds. Morphologic changes occurred in CD45+
      leukocytes and higher levels for several cytokines were detected in the stromal
      wound bed within minutes following dulled-blade wounds. Flow cytometry showed
      significantly more monocytes (CD45+/CD11b+/Ly6C+) and gammadeltaT cells
      (CD45+/GL3+) recruited into the corneas of mice with dulled-blade wounds by 6
      hours. CONCLUSIONS: Differences in cytokine-driven leukocyte responses are seen
      after dulled-blade debridement compared with rotating-burr injury.

PMID- 24677105
TI  - Quantitative fundus autofluorescence in recessive Stargardt disease.
AB  - PURPOSE: To quantify fundus autofluorescence (qAF) in patients with recessive
      Stargardt disease (STGD1). METHODS: A total of 42 STGD1 patients (ages: 7-52
      years) with at least one confirmed disease-associated ABCA4 mutation were
      studied. Fundus AF images (488-nm excitation) were acquired with a confocal
      scanning laser ophthalmoscope equipped with an internal fluorescent reference to
      account for variable laser power and detector sensitivity. The gray levels (GLs)
      of each image were calibrated to the reference, zero GL, magnification, and
      normative optical media density to yield qAF. Texture factor (TF) was calculated
      to characterize inhomogeneities in the AF image and patients were assigned to the
      phenotypes of Fishman I through III. RESULTS: Quantified fundus autofluorescence
      in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for
      age. Young patients exhibited the relatively highest qAF, with levels up to 8
      fold higher than healthy eyes. Quantified fundus autofluorescence and TF were
      higher in Fishman II and III than Fishman I, who had higher qAF and TF than
      healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than
      most other patients, even in the presence of a second allele associated with
      severe disease. CONCLUSIONS: Quantified fundus autofluorescence is an indirect
      approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations
      cause significantly elevated qAF, consistent with previous reports indicating
      that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative
      differences in fundus AF images are not evident, qAF can elucidate phenotypic
      variation. Quantified fundus autofluorescence will serve to establish genotype
      phenotype correlations and as an outcome measure in clinical trials.

PMID- 24677106
TI  - A role for ELOVL4 in the mouse meibomian gland and sebocyte cell biology.
AB  - PURPOSE: The meibum lipidome contains lipids with extremely long chain fatty acid
      (ELCFA) residues, longer than C28. Particular lipids based on extremely long
      chain (O-acyl)-omega-hydroxy fatty acids (OAHFA) are found in all mammal meibum
      and are proposed to stabilize the tear film by forming the interphase between its
      lipid and aqueous sublayers. The enzyme ELOVL4 is required for synthesis of
      ELCFA. We investigated whether Stgd3 mice, harboring mutations in ELOVL4 that
      have been shown to decrease the levels of its biosynthetic lipid products, would
      represent a model system in which to define the role of such lipids in meibum.
      METHODS: Ocular phenotypes of wild-type mice were compared with those of Stgd3
      mice. ELOVL4 expression in eyelid and back skin was characterized by
      immunohistochemical analysis. Anatomical changes within the eyelids of mutant
      mice were examined by hematoxylin and eosin staining of paraffin-embedded tissue.
      RESULTS: Mutant mice had increased eyelid blink rates, a reluctance to maintain
      their eyes fully open, protruding meibomian gland (MG) orifices, and anatomical
      changes within the MG. In wild-type mice, ELOVL4 was strongly expressed within
      the holocrine meibomian and sebaceous glands. The enzyme localized to structures
      encircling lipid deposits within cells in both the early and late stages of
      differentiation. No ELOVL4 was detected within the central meibomian duct.
      CONCLUSIONS: Stgd3 mice show changes that resemble clinical findings in patients
      with the evaporative type of dry eye disease, suggesting that further studies in
      this mouse model will provide a basis for better understanding of the causes of
      human dry eye.

PMID- 24677107
TI  - Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in
      retinal microglia.
AB  - PURPOSE: Retinal microglia become activated in diabetes and produce pro
      inflammatory molecules associated with changes in retinal vasculature and
      increased apoptosis of retinal neurons and glial cells. We sought to determine if
      the action of aldose reductase (AR), an enzyme linked to the pathogenesis of
      diabetic retinopathy, contributes to activation of microglial cells. METHODS:
      Involvement of AR in the activation process was studied using primary cultures of
      retinal microglia (RMG) isolated from wild-type and AR-null mice, or in mouse
      macrophage cultures treated with either AR inhibitors or small interfering RNA
      (siRNA) directed to AR. Inflammatory cytokines were measured by ELISA. Cell
      migration was measured using a transwell assay. Gelatin zymography was used to
      detect active matrix metalloproteinase (MMP)-9, while RMG-induced apoptosis of
      adult retinal pigment epithelium (ARPE-19) cells was studied in a cell coculture
      system. RESULTS: Aldose reductase inhibition or genetic deficiency substantially
      reduced lipopolysacharide (LPS)-induced cytokine secretion from macrophages and
      RMG. Aldose reductase inhibition or deficiency also reduced the activation of MMP
      9 and attenuated LPS-induced cell migration. Additionally, blockade of AR by
      sorbinil or through genetic means caused a reduction in the ability of activated
      RMG to induce apoptosis of ARPE-19 cells. CONCLUSIONS: These results demonstrate
      that the action of AR contributes to the activation of RMG. Inhibition of AR may
      be a therapeutic strategy to reduce inflammation associated with activation of
      RMG in disease.

PMID- 24677109
TI  - Corneal biomechanical properties at different corneal cross-linking (CXL)
      irradiances.
AB  - PURPOSE: New corneal cross-linking (CXL) devices are capable of using higher UV-A
      light irradiances than used in original CXL protocols. The Bunsen-Roscoe law
      states that a photochemical reaction should stay constant if the delivered total
      energy is kept constant; however, little clinical data are available to support
      this hypothesis. METHODS: We investigated the biomechanical properties of four
      groups (n = 50 each) of porcine corneas. Three groups were exposed to riboflavin
      0.1 % and UV-A irradiation of equal total energy (3 mW/cm(2) for 30 minutes, 9
      mW/cm(2) for 10 minutes, and 18 mW/cm(2) for 5 minutes). Controls were exposed to
      riboflavin 0.1% without irradiation. Young's modulus of 5-mm wide corneal strips
      was used as an indicator of corneal stiffness. RESULTS: We observed a decreased
      stiffening effect with increasing UV-A intensity. Young's modulus at 10% strain
      showed significant differences between 3 mW/cm(2) and 9 mW/cm(2) (P = 0.002), 3
      mW/cm(2) and 18 mW/cm(2) (P = 0.0002), 3 mW/cm(2) and the control group (P <
      0.0001), and 9 mW/cm(2) and the control group (P = 0.015). There was no
      difference between 18 mW/cm(2) and the control group (P = 0.064) and between 9
      mW/cm(2) and 18 mW/cm(2) (P = 0.503). CONCLUSIONS: The biomechanical effect of
      CXL decreased significantly when using high irradiance/short irradiation time
      settings. Intrastromal oxygen diffusion capacity and increased oxygen consumption
      associated with higher irradiances may be a limiting factor leading to reduced
      treatment efficiency. Our results regarding the efficiency of high-irradiance
      collagen cross-linking (CXL) raise concerns about the clinical efficiency of the
      new high-irradiance CXL devices already used in clinical practice without proper
      validation.

PMID- 24677108
TI  - Retinal pigment epithelial cell death by the alternative complement cascade: role
      of membrane regulatory proteins, calcium, PKC, and oxidative stress.
AB  - PURPOSE: Retinal pigment epithelial (RPE) cell death is an important feature of
      the advanced forms of AMD. Complement alternative pathway (AP) activation is
      associated with RPE cell death in AMD. In this study, we developed a new model to
      initiate AP activation on RPE cells and investigated the cellular mechanisms
      modulating AP activation-mediated RPE cell death. METHODS: An anti-RPE antibody
      was developed. A spontaneously arising human RPE cell line (ARPE-19) and donor
      RPE cells were primed with this antibody followed by stimulation with 6% C1q
      depleted human serum (C1q-Dep) to activate AP. Complement activation was
      evaluated by flow cytometry and immunofluorescent staining. Cellular response to
      complement activation was examined by measurement of intracellular calcium and
      adenosine triphosphate (ATP) release. Cell viability was assessed by Sytox
      orange, tetrazolium salt, and lactate dehydrogenase release assays. RESULTS:
      Alternative pathway complement-mediated RPE cell death was associated with
      membrane attack complex formation and a rapid rise in intracellular calcium
      followed by release of ATP. Downregulation of membrane complement regulatory
      proteins and protein kinase C (PKC) inhibition increased cell susceptibility to
      complement attack. Pretreatment of RPE cells with either hydrogen peroxide or
      hydroquinone enhanced cell death. Chronic repetitive treatment of RPE cells with
      low levels of oxidants also enhanced complement-mediated cell death. CONCLUSIONS:
      Activation of complement through the alternative pathway induces sublytic and
      lytic phases of complement attack on RPE cells, leading to cell death modulated
      by extracellular calcium, membrane complement regulatory proteins, and
      intracellular signaling mechanisms. Single-dose oxidant exposure and low-dose
      repetitive oxidant exposure rendered RPE cells more susceptible to complement
      mediated death.

PMID- 24677110
TI  - Difluprednate 0.05% versus prednisolone acetate 1% for endogenous anterior
      uveitis: a phase III, multicenter, randomized study.
AB  - PURPOSE: Endogenous anterior uveitis (AU), when untreated, may lead to vision
      loss. This study compared the safety and efficacy of difluprednate versus
      prednisolone acetate for the treatment of this condition. METHODS: This phase
      III, double-masked, noninferiority study randomized patients with mild to
      moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily,
      alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54)
      eight times daily. The 14-day treatment period was followed by a 14-day dose
      tapering period and a 14-day observation period. The primary efficacy end point
      was change in anterior chamber cell grade (range, 0 for <=1 cell to 4 for >50
      cells) from baseline to day 14. RESULTS: At day 14, the mean change in anterior
      chamber cell grade with difluprednate was noninferior to that with prednisolone
      acetate (-2.2 vs. -2.0, P = 0.16). The proportions of difluprednate-treated
      patients versus prednisolone acetate-treated patients demonstrating complete
      clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and
      at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group
      difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for
      difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate-treated
      patients, P = 0.0013) but not at other time points. The mean IOP values in both
      groups remained less than 21 mm Hg throughout the study. CONCLUSIONS:
      Difluprednate 0.05% four times daily is well tolerated and is noninferior to
      prednisolone acetate 1% eight times daily for the treatment of endogenous AU.
      (ClinicalTrials.gov number, NCT01201798.).

PMID- 24677111
TI  - Recent structural alteration of the peripheral lamina cribrosa near the location
      of disc hemorrhage in glaucoma.
AB  - PURPOSE: We investigated whether disc hemorrhage (DH) is associated with the
      recent structural alteration of the peripheral lamina cribrosa (LC) as assessed
      by enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD
      OCT). METHODS: Serial horizontal B-scan images were obtained by EDI SD-OCT from
      primary open-angle glaucoma (POAG) patients before and after the detection of DH
      (DH group, n = 45), and those who had no DH during the 1-year scan interval (non
      DH group, n = 36). The images were processed using compensation and contrast
      enhancement. Then, 11 radial OCT images centered on the optic disc were generated
      from the 3-dimensionally reconstructed volume image. A recent structural
      alteration of the LC was defined when either the outward deformation of the
      anterior LC surface or radial disruption of the LC was identified in the temporal
      periphery. RESULTS: A recent structural alteration of the LC was found in 40
      (88.9%) eyes in the DH group versus 4 (11.1%) eyes in the non-DH group. The
      amount of maximum outward deformation (55.82 +/- 34.60 vs. 20.15 +/- 4.28 MUm)
      and radial disruption (69.87 +/- 46.74 vs. 18.31 +/- 1.17 MUm) was larger in the
      DH group than in the non-DH group. The maximum LC alteration was observed within
      1 clock-hour distance from the location of DH in all 40 eyes. CONCLUSIONS: The
      peripheral LC exhibited a recent alteration in eyes with DH. The alteration was
      correlated spatially with the location of the DH. These findings suggest that DH
      may result from microvascular damage incurred from alteration of the LC near its
      insertion.

PMID- 24677113
TI  - Evidence for subclinical H5N1 avian influenza infections among Nigerian poultry
      workers.
AB  - In recent years Nigeria has experienced sporadic incursions of highly pathogenic
      H5N1 avian influenza among poultry. In 2008, 316 poultry-exposed agricultural
      workers, and 54 age-group matched non-poultry exposed adults living in the Enugu
      or Ebonyi States of Nigeria were enrolled and then contacted monthly for 24
      months to identify acute influenza-like-illnesses. Annual follow-up sera and
      questionnaire data were collected at 12 and 24 months. Participants reporting
      influenza-like illness completed additional questionnaires, and provided nasal
      and pharyngeal swabs and acute and convalescent sera. Swab and sera specimens
      were studied for evidence of influenza A virus infection. Sera were examined for
      elevated antibodies against 12 avian influenza viruses by microneutralization and
      3 human viruses by hemagglutination inhibition. Four (3.2%) of the 124 acute
      influenza-like-illness investigations yielded molecular evidence of influenza,
      but virus could not be cultured. Serial serum samples from five poultry-exposed
      subjects had a >=4-fold change in microneutralization titers against
      A/CK/Nigeria/07/1132123(H5N1), with three of those having titers >=1:80 (maximum
      1:1,280). Three of the five subjects (60%) reported a preceding influenza-like
      illness. Hemagglutination inhibition titers were >=4-fold increases against one
      of the human viruses in 260 participants. While cross-reactivity from antibodies
      against other influenza viruses cannot be ruled out as a partial confounder, over
      the course of the 2-year follow-up, at least 3 of 316 (0.9%) poultry-exposed
      subjects had evidence for subclinical HPAI H5N1 infections. If these data
      represent true infections, it seems imperative to increase monitoring for avian
      influenza among Nigeria's poultry and poultry workers.

PMID- 24677112
TI  - Grouping of behavioural and psychological symptoms of dementia.
AB  - OBJECTIVE: A wide range of behavioural and psychological symptoms (BPSD) are
      common in dementia, and it has been suggested that groups of correlated symptoms
      should be studied together. Here, we describe the groups of BPSD that have been
      identified in the literature and how they have been used to study associations,
      burden, treatment and underlying biology. METHODS: The literature database PubMed
      was searched for articles that identified clusters or factors of BPSD or used
      previously defined symptom groups. RESULTS: Sixty-two studies were included.
      Generally, the following symptom groups were suggested: affective symptoms,
      including depression and anxiety; psychosis, including delusions and
      hallucinations; hyperactivity, including irritability and aggression; and
      euphoria. Symptoms that did not show consistent results include apathy, eating
      disturbances, night-time behaviour disturbances, disinhibition and aberrant motor
      behaviour. Symptom groups differed in their associations, treatment and biology.
      CONCLUSIONS: Studies investigating symptom groups show relatively consistent
      results. Studying symptom groups allows similar symptoms to be studied together,
      which might strengthen results and may point to differences in their aetiology
      and treatment. However, a large amount of the individual variability of the
      symptoms could not be explained by the factors, and authors should carefully
      address their research question and hypotheses to decide if symptoms should be
      studied in groups or individually. Clinicians need to consider each symptom in
      its own right and also to be aware of the interrelations between them when
      assessing patients and developing strategies for treatment.

PMID- 24677114
TI  - Knockdown of S100P by lentiviral-mediated RNAi promotes apoptosis and suppresses
      the colony-formation ability of gastric cancer cells.
AB  - S100P is a putative candidate oncogene in several types of human tumors. However,
      expression of S100P, its potential role and its clinical significance in gastric
      cancer remain unclear. In the present study, S100P expression was examined by
      immunohistochemistry using a tissue microarray. Positive staining for S100P was
      noted in 77.1% of the cases while 22.9% were negative. In two gastric cancer cell
      lines, MGC-803 and SGC-7901, S100P expression was knocked down by a lentiviral
      short hairpin delivery system. The RNA interference-mediated downregulation of
      S100P expression markedly promoted cell apoptosis and inhibited cell colony
      formation ability of the gastric cancer cells. In addition, knockdown of S100P
      significantly regulated the expression of 12 apoptosis-associated genes with a
      >1.5-fold change compared with the negative control. Among them, FOS, DDIT3 and
      FN1 were significantly upregulated, while FASLG, DAPK1, CTNNB1 and CASP2 were
      notably downregulated following S100P silencing. These results suggest that S100P
      acts as an oncogenic factor in gastric cancer and is a potential molecular target
      for gastric cancer gene therapy.

PMID- 24677115
TI  - Role of interleukin-6 in differentiating interleukin-11 induced fever and early
      bacterial infection.
AB  - OBJECTIVE: To evaluate the role of Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10,
      TNF-alpha, IFN-gamma) in differentiating interleukin 11 induced fever with C
      reactive protein elevation from early bacterial infection. METHODS: A total of 74
      patients were enrolled in this retrospective study. Serum Th1/Th2 cytokines were
      determined using cytometric bead array (CBA) techniques. Whenever the patients
      had febrile disease or elevated CRP, systemic inflammatory signs, procalcitonin
      (PCT), blood culture and X-ray examination were done. The patients were assigned
      into infected and non-infected groups based on the clinical and laboratory
      findings. RESULTS: The CRP levels in both the groups were significantly
      increased, but no statistically significant difference was found (P = 0.574). IL
      6 levels of the infected group were significantly elevated with simultaneously
      elevated IL-10 levels in a proportion of the patients. IL-6 levels of non
      infected patients were normal. IL-6 and IL-10 levels of infected patients were
      significantly higher than those of non-infected patients (P = 0.005, 0.015,
      respectively). CONCLUSIONS: For the patients treated with recombinant human
      interleukin 11 (rhIL-11), IL-6 and IL-10 measurements can be a useful adjuvant
      tool for the differentiation of rhIL-11 induced fever with C-reactive protein
      elevation from early bacterial infection.

PMID- 24677116
TI  - Is distal fibular fracture an absolute contraindication to free fibular flap
      harvesting? A review of evidence in the literature and illustration by a
      successful case.
AB  - Despite the advantages of a fibula flap, many surgeons would often be hesitant in
      its use in patients with a history of distal fibular fracture. The chief concern
      is the potential vascular damage sustained during the injury. From our
      experience, however, we noticed that the blood supply of various components of a
      fibula flap rarely relies on its distal part alone. Avoiding the use of this flap
      may unnecessarily forgo the optimal reconstructive option in many patients. Free
      fibula flap was harvested from a 41-year-old man who had a history of left fibula
      fracture 10 years before surgery. The fracture was treated with open reduction
      with internal fixation. The plate was removed 1 year after the trauma surgery. We
      used this fractured and healed fibula to reconstruct the intraoral and mandibular
      defect after tumor extirpation. The harvesting process was straight-forward and
      the flap survived uneventfully. On the basis of our experience and current
      evidence in the literature, we believe that a history of previous fibular
      fracture should not be considered as an absolute contraindication for free
      fibular flap harvesting. With a good knowledge of the lower limb anatomy and
      appropriate patient selection, the fibular flap can still be a safe option that
      incurs no additional risk.

PMID- 24677117
TI  - Effect of esomeprazole with/without acetylsalicylic acid, omeprazole and
      lansoprazole on pharmacokinetics and pharmacodynamics of clopidogrel in healthy
      volunteers.
AB  - OBJECTIVE: The effect of proton pump inhibitors (PPIs) on the pharmacokinetics
      and pharmacodynamics of clopidogrel was assessed in two healthy volunteer
      crossover studies. SUBJECTS AND METHODS: Study 1: subjects received clopidogrel
      alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs
      (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for
      29 days in three treatment periods (randomized treatment sequence assignment).
      Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and
      clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination
      esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two
      treatment periods (randomized treatment sequence assignment). Pharmacokinetic
      effects were estimated by measuring active metabolite of clopidogrel, and
      pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced
      platelet aggregation. RESULTS: There was a relative decrease of up to 50 % in
      exposure to the active metabolite of clopidogrel with the different PPIs (study
      1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with
      clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of
      ADP-induced platelet aggregation with co-administration of different PPIs,
      compared with clopidogrel alone; however, no differences in platelet inhibition
      were observed during co-administration with the esomeprazole/low-dose ASA fixed
      dose combination. CONCLUSION: Omeprazole, esomeprazole and lansoprazole decreased
      systemic exposure to the active metabolite of clopidogrel in healthy volunteers,
      leading to modest decreases in its antiplatelet effect. However, no apparent
      differences in platelet inhibition were observed when esomeprazole was co
      administered with low-dose ASA as a fixed-dose combination.

PMID- 24677118
TI  - Inverted colloidal quantum dot solar cells.
AB  - An inverted architecture of quantum dot solar cells is demonstrated by
      introducing a novel ZnO method on top of the PbS CQD film. Improvements in device
      characteristics stem from constructive optical interference from the ZnO layer
      that enhances absorption in the PbS CQD layer. Outstanding diode characteristics
      arising from a superior PbS/ZnO junction provide a further electronic advantage. 

PMID- 24677119
TI  - Oral health status of fishermen and non-fishermen community of Kutch district,
      Gujarat, India: a comparative study.
AB  - BACKGROUND: Fishing is one such hazardous occupation, which involves irregular
      diet, stress, alcoholism, tobacco and pernicious habits. Fishermen have lower
      socio-economic status and their illiteracy adds to their poor oral hygiene, which
      may influence general and oral health. AIM: The aim of the study was to assess
      and compare the oral health status of fishermen and non-fishermen population of
      Kutch District, Gujarat, India. MATERIALS AND METHODS: A descriptive cross
      sectional survey was conducted to assess and compare the oral health status of
      the fishermen and non-fishermen community of Mundra taluka of Kutch district,
      Gujarat, India, from January 2013 to June 2013. RESULTS: Fishermen had
      significantly higher periodontal disease and dental caries than non-fishermen
      group (p = 0.001). Malocclusion was significantly higher in non-fishermen group
      (p = 0.001). Extraction was the most prevalent treatment need among both groups.
      Occupation and educational status were respectively identified as the best
      predictors for dental caries and periodontal disease. CONCLUSIONS: Findings of
      the present study suggest that oral health status of the fishermen population was
      relatively poor, with high caries prevalence and poor periodontal health when
      compared to the non-fishermen population. In the light of high treatment needs of
      the study population, health policy that emphasises oral health promotion and
      prevention would seem more advantageous in addition to traditional curative care.

PMID- 24677120
TI  - Briefing notes on emergency medical disembarks by helicopter at sea in North
      America.
AB  - Physicians and nurses from shore based practice who move to work on cruise ships
      often have concerns about the management of critically ill patients and questions
      about the resources available to transfer by helicopter to a tertiary care
      facility. This article seeks to outline some of the clinical, operational and
      logistical issues associated with using a helicopter to transfer a patient from a
      ship to a shore-side hospital. While it focuses on resources available in the
      maritime areas around North America, most of the clinical comments would apply to
      helicopter evacuations anywhere in the world. 

PMID- 24677121
TI  - Legal aspects of cruise medicine - can a non-US ship's doctor be sued for
      malpractice in Florida?
AB  - An English ship's doctor treated a non-US female patient for abdominal discomfort
      on a foreign-flagged cruise ship off the coast of Haiti. In Mexico the patient
      underwent abdominal surgery, followed by complications, for which her lawyers
      wanted to take the ship's doctor to court in Florida, USA. A trial court granted
      their wish, but this decision was reversed on appeal as the factors discussed
      were insufficient to establish Florida jurisdiction over the ship's doctor. The
      decision is not about whether malpractice occurred; it is about limiting the
      possibility of taking the ship's doctor to a court in a location preferred by the
      plaintiffs' lawyers. The appeal court ruling is important for non-US doctors
      working as independent contractors on cruise vessels that visit US ports, and it
      will hopefully prevent some of the more frivolous law suits from being filed in
      the future. 

PMID- 24677122
TI  - Long-lasting adverse effects after short-term low-dose treatment with
      metoclopramide for vomiting.
AB  - Metoclopramide is commonly used to treat vomiting caused by seasickness and acute
      gastroenteritis on cruise ships and serious adverse effects have not been
      reported from use at sea. We report severe long-lasting adverse effects in a
      young female seafarer following short-term, low-dose use of metoclopramide.
      During rough seas a 25-year-old female musician on a cruise vessel presented with
      nausea and vomiting. She was given intramuscular metoclopramide 10 mg and
      diphenhydramine 25 mg. Vomiting stopped after the injections, but she felt tired,
      confused and dizzy. She then had been taking metoclopramide 5-10 mg a day, but
      stopped after a total per oral dose of 30 mg as she developed disturbing symptoms
      that she related to the medication, including dizziness, anxiety, fatigue,
      depression and involuntary movements (twitches, jerks, ticks, and tremors of the
      eyelids, tongue, neck, fingers, arms and legs). Neurological examination, blood
      tests, electrocardiography and magnetic resonance imaging of the brain were all
      normal. Although gradually reduced in strength and frequency, the adverse effects
      were very disturbing for about 10 months, but at 13 months she was almost fully
      recovered. For many years numerous vomiting sea travellers have been successfully
      treated with a single parenteral 10 mg dose of metoclopramide. There are no
      obvious reasons why our previously healthy patient experienced such serious and
      long-lasting side effects after low-dose, short-term metoclopramide
      administration. Until more is known, metoclopramide should be reserved for
      debilitating cases - and only be given after other remedies have been tried and
      found ineffective. 

PMID- 24677123
TI  - Acute gastroenteritis and video camera surveillance: a cruise ship case report.
AB  - A 'faecal accident' was discovered in front of a passenger cabin of a cruise
      ship. After proper cleaning of the area the passenger was approached, but denied
      having any gastrointestinal symptoms. However, when confronted with surveillance
      camera evidence, she admitted having the accident and even bringing the towel
      stained with diarrhoea back to the pool towels bin. She was isolated until the
      next port where she was disembarked. Acute gastroenteritis (AGE) caused by
      Norovirus is very contagious and easily transmitted from person to person on
      cruise ships. The main purpose of isolation is to avoid public vomiting and
      faecal accidents. To quickly identify and isolate contagious passengers and crew
      and ensure their compliance are key elements in outbreak prevention and control,
      but this is difficult if ill persons deny symptoms. All passenger ships visiting
      US ports now have surveillance video cameras, which under certain circumstances
      can assist in finding potential index cases for AGE outbreaks. 

PMID- 24677124
TI  - Selected epidemiological aspects of fresh whole blood application in the Polish
      Field Hospital in Afghanistan.
AB  - Minimisation of blood transmitted diseases is a basic element of all blood
      transfusion strategies. Civilian health service standards used in peacetime may
      be difficult to implement in a battlefield. The risk of blood-borne diseases
      depends on the applied donor qualification procedures and the epidemiological
      situation in the areas of military operations. The authors discuss various
      epidemiological aspects considered when selecting potential donors of fresh whole
      blood for a Walking Blood Bank at the Polish Field Hospital in Afghanistan. 

PMID- 24677125
TI  - Psychological distress in families of victims of maritime piracy - the Italian
      experience.
AB  - BACKGROUND: This work has investigated the psychological status of family members
      of kidnapped seafarers, 5 months after their release. AIM: The goal of this study
      was to assess if relatives of victims of maritime piracy showed signs of
      psychological distress, to diagnose eventual pathologies and to measure their
      severity. MATERIALS AND METHODS: Twelve family members (8 females and 4 males) of
      4 kidnapped seafarers were examined. They were first interviewed by a semi
      structured approach and then examined using the self-report questionnaire State
      Trait Anxiety Inventory (STAI-Y), and the Hamilton Depression Rating Scale
      (HDRS). RESULTS: Five months after the relatives had been released, 42% of the
      family members of kidnapped seafarers obtained pathological scores in the STAI-Y
      questionnaire, and 33% showed depression according to the HDRS. CONCLUSIONS:
      Family members of kidnapped seafarers show significant psychopathological
      symptoms 5 months after relatives have been released. Symptoms may be severe
      enough to interfere with daily life in about one half of them. Kidnapping is a
      changing life experience and both victims and relatives require attention and
      support.

PMID- 24677126
TI  - Dynamics of stress as a predictor of health consequences in Polish drilling
      platform workers. Longitudinal study: part I.
AB  - BACKGROUND AND AIM: The subject of presented article is the evaluation of the
      relationship between the way of adaptation to work-related stress and chosen
      health indicators among drilling platform workers in Poland. The study procedure
      is a longitudinal research, including data analysis from 1993 to 2013. MATERIALS
      AND METHODS: 167 Polish platform male workers with an average age of 42 years
      have been examined. The studies include, according to the triangulation method,
      data from 3 sources: data concerning the so-called 'objective' and 'subjective'
      stress, personality and temperamental examinations and data concerning health
      state. RESULTS: Stress affects health negatively, the higher subjective and
      objective stress, the worse health indicators: higher body mass index, more
      declared health ailments and worse evaluation of personal health (r = -0.23).
      Stress also affects health via 2 indirect tracts: through the kind of stress
      adaptation (stress dynamics) (r = -0.43) and through coping - depositional stress
      coping style (r = 0.41). CONCLUSIONS: Stress adaptation (stress dynamics) and
      coping style included in the study in longer perspective show that those drilling
      platform workers, who declare the decrease of stress over the years, present
      worse health indicators than those, who declare variability in the ways of
      adaptation to stress.

PMID- 24677127
TI  - Bernardino Ramazzini (1633-1714): an often forgotten pioneer in maritime health.

PMID- 24677128
TI  - Classic versus millennial medical lab anatomy.
AB  - This study investigated the integration, implementation, and use of cadaver
      dissection, hospital radiology modalities, surgical tools, and AV technology
      during a 12-week contemporary anatomy course suggesting a millennial laboratory.
      The teaching of anatomy has undergone the greatest fluctuation of any of the
      basic sciences during the past 100 years in order to make room for the meteoric
      rise in molecular sciences. Classically, anatomy consisted of a 2-year
      methodical, horizontal, anatomy course; anatomy has now morphed into a 12-week
      accelerated course in a vertical curriculum, at most institutions. Surface and
      radiological anatomy is the language for all clinicians regardless of specialty.
      The objective of this study was to investigate whether integration of full-body
      dissection anatomy and modern hospital technology, during the anatomy laboratory,
      could be accomplished in a 12-week anatomy course. Literature search was
      conducted on anatomy text, journals, and websites regarding contemporary hospital
      technology integrating multiple image mediums of 37 embalmed cadavers, surgical
      suite tools and technology, and audio/visual technology. Surgical and radiology
      professionals were contracted to teach during the anatomy laboratory. Literature
      search revealed no contemporary studies integrating full-body dissection with
      hospital technology and behavior. About 37 cadavers were successfully imaged with
      roentograms, CT, and MRI scans. Students were in favor of the dynamic laboratory
      consisting of multiple activity sessions occurring simultaneously. Objectively,
      examination scores proved to be a positive outcome and, subjectively, feedback
      from students was overwhelmingly positive. Despite the surging molecular based
      sciences consuming much of the curricula, full-body dissection anatomy is
      irreplaceable regarding both surface and architectural, radiological anatomy.
      Radiology should not be a small adjunct to understand full-body dissection, but
      rather, full-body dissection aids the understanding of radiology mediums. The
      millennial anatomy dissection laboratory should consist of, at least, 50%
      radiology integration during full-body dissection. This pilot study is an example
      of the most comprehensive integration of full-body dissection, radiology, and
      hospital technology.

PMID- 24677129
TI  - Lycopene cyclase and phytoene synthase activities in the marine yeast
      Rhodosporidium diobovatum are encoded by a single gene crtYB.
AB  - crtYB, encoding lycopene cyclase and phytoene synthase was cloned from
      Rhodosporidium diobovatum ATCC 2527 by rapid amplification of cDNA ends method.
      The full-length cDNA of crtYB is 2, 330 bp and contains eight introns. The gene
      products is a 594 amino acids, with a predicted molecular mass of 65.63 kDa and a
      pI of 6.73. The N-terminus of the protein contains six transmembrane regions,
      which has been characterized as a lycopene beta-cyclase. The C-terminal half has
      squalene and phytoene synthase signatures that identified as phytoene synthetase.
      By heterologous complementary detection of this gene in E. coli and HPLC
      analysis, the regions responsible for phytoene synthesis and lycopene cyclization
      were localized within the protein.

PMID- 24677130
TI  - Semiconductor alloy nanoribbon lateral heterostructures for high-performance
      photodetectors.
AB  - High-performance visible-light photodetectors are achieved based on single
      nanoribbon lateral heterostructures composed of two different semiconductor
      alloys epitaxially grown in the lateral direction. They reveal superior spectral
      response range, responsivity, Ion/Ioff ratio, and external quantum efficiency,
      relative to devices based on single composition structures.

PMID- 24677131
TI  - Survival in infection-related acute-on-chronic liver failure is defined by
      extrahepatic organ failures.
AB  - Infections worsen survival in cirrhosis; however, simple predictors of survival
      in infection-related acute-on-chronic liver failure (I-ACLF) derived from
      multicenter studies are required in order to improve prognostication and resource
      allocation. Using the North American Consortium for Study of End-stage Liver
      Disease (NACSELD) database, data from 18 centers were collected for survival
      analysis of prospectively enrolled cirrhosis patients hospitalized with an
      infection. We defined organ failures as 1) shock, 2) grade III/IV hepatic
      encephalopathy (HE), 3) need for dialysis and mechanical ventilation.
      Determinants of survival with these organ failures were analyzed. In all, 507
      patients were included (55 years, 52% hepatitis C virus [HCV], 15.8% nosocomial
      infection, 96% Child score >= 7) and 30-day evaluations were available in 453
      patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial
      peritonitis (SBP) (22.5%) were the most prevalent infections. During
      hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal
      replacement, and 15.8% needed ventilation; 23% died within 30 days and 21.6%
      developed second infections. Admitted patients developed none (38.4%), one
      (37.3%), two (10.4%), three (10%), or four (4%) organ failures. The 30-day
      survival worsened with a higher number of extrahepatic organ failures, none
      (92%), one (72.6%), two (51.3%), three (36%), and all four (23%). I-ACLF was
      defined as >= 2 organ failures given the significant change in survival
      probability associated at this cutoff. Baseline independent predictors for
      development of ACLF were nosocomial infections, Model for Endstage Liver Disease
      (MELD) score, low mean arterial pressure (MAP), and non-SBP infections.
      Independent predictors of poor 30-day survival were I-ACLF, second infections,
      and admission values of high MELD, low MAP, high white blood count, and low
      albumin. CONCLUSION: Using multicenter study data in hospitalized decompensated
      infected cirrhosis patients, I-ACLF defined by the presence of two or more organ
      failures using simple definitions is predictive of poor survival.

PMID- 24677132
TI  - Socio-economic differences in use of prescribed and over-the-counter medicine for
      pain and psychological problems among Danish adolescents--a longitudinal study.
AB  - The objective for this study was to investigate socio-economic status (SES)
      differentials in the use of over-the-counter and prescribed medicine for pain and
      psychological problems among adolescents. Data consisted of questionnaire data on
      medicine use and health status, collected from 17- to 18-year-old adolescents (n
      = 2,400) during second round of the West Jutland cohort study 2007, and register
      data on prescribed medicine use, parental educational level and household income.
      We used multiple logistic regression analysis to calculate odd ratios for self
      reported and register-based use of medicine for pain and psychological problems
      according to parental educational level and household income. Young girls used
      twice as much medicine for pain and psychological problems compared to young
      boys. SES differences based on parental educational level were directly
      associated with the use of prescribed medicine for psychological problems, and
      SES differences based on household income were directly associated with overall
      medicine use and use of over-the-counter medicine. Some of the SES differentials
      disappeared or decreased after adjusting for health status. There were no SES
      differentials in the use of prescribed medicine for pain. CONCLUSION: The risk of
      use of prescribed medicine for psychological problems increased in adolescents
      with decreasing parental education, while the risk of overall medicine use and
      use of over-the-counter medicine was increased in adolescents from low household
      income. Furthermore, the results indicate that some of the SES differentials in
      medicine use could be explained by a difference in health status across SES.

PMID- 24677133
TI  - Purpura, petechiae, and bullae as first signs of juvenile granulomatosis with
      polyangiitis.
AB  - We present a case of a 14-year-old girl who had a severe form of granulomatosis
      with polyangiitis (GPA) with extensive dermatological involvement, whose initial
      presentation was nonspecific leading to diagnostic confusion and initial
      consideration of infectious and other vasculitis causes. The patient presented
      with fever, congestion, malaise, and sinus pain. She was diagnosed with bacterial
      sinusitis and treated with antibiotics. Within weeks, she developed abdominal
      pain, hematuria, migratory arthritis, and palpable purpura and was diagnosed with
      Henoch-Schonlein purpura. She went on to develop hemoptysis and progression of
      the rash into erosive bullae. Investigations revealed that she was ANCA positive
      and had pauci-immune glomerulonephritis. Given her upper airway, pulmonary and
      renal involvement, and antineutrophil cytoplasmic antibodies positivity, a
      definitive diagnosis of a severe form of GPA was made. GPA is a chronic
      relapsing, life threatening vasculitis that predominantly affects small vessels.
      CONCLUSION: Our case demonstrates that GPA can present initially with nonspecific
      symptoms, including extensive dermatological involvement, leading to diagnostic
      confusion, and delays in treatment. In the case of a severe peripheral rash in
      the juvenile population and/or resistant upper airway symptoms, it is vital to
      consider a diagnosis of GPA to avoid serious organ or life threatening
      consequences.

PMID- 24677135
TI  - Suppressive role of miR-502-5p in breast cancer via downregulation of TRAF2.
AB  - TRAF2 promotes cancer cell survival, proliferation and metastasis through the NF
      kappaB pathway by directly interacting with various TNF recepors. However, the
      molecular mechanism of TRAF2 dysregulation in breast cancer remains to be
      elucidated. In the present study, miR-502-5p was predicted as a potential
      regulator of TRAF2. miR-502-5p was significantly downregulated in breast cancer
      tissues when compared to the level in paired normal breast tissues. The breast
      cancer cell lines including MCF-7 and MDA-MB-231 expressed a lower level of miR
      502-5p when compared to the level in the non-malignant breast epithelial cell
      line MCF-10A. In vitro, miR-502-5p enhanced early apoptosis and inhibited
      proliferation of breast cancer cells. Luciferase reporter assay results showed
      that miR-502-5p could bind to the 3'-untranslated region of the TRAF2 gene, thus,
      exerting an inhibitory effect on TRAF2. Furthermore, silencing of TRAF2 exhibited
      effects similar to those of exogenous miR-502-5p, while overexpression of TRAF2
      partially abrogated miR-502-5p-mediated suppression in breast cancer cells. In
      conclusion, miR-502-5p may act as a tumor-suppressor gene by targeting oncogenic
      TRAF2 in breast cancer and, therefore, may be a potential diagnostic and
      anticancer therapeutic marker for breast cancer.

PMID- 24677137
TI  - Circulating pro- and anti-angiogenic mediators in patients infected with
      hepatitis C at different stages of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a hypervascular tumor characterized by
      neovascularization. The objective of the current study was to determine
      circulating proangiogenic [vascular endothelial growth factor (VEGF), platelet
      derived growth factor (PDGF), and tumor necrosis factor (TNF-alpha)] and
      antiangiogenic [IL-4, IL-12, interferon gamma-induced protein 10 (IP-10), and
      angiostatin] factors in Egyptian patients with different stages of HCC. Enzyme
      linked immunosorbent assay (ELISA) was used to detect the concentrations of these
      mediators in plasma of 135 HCC patients (57 Child-Pugh A, 24 Child-Pugh B, and 54
      Child-Pugh C stage) and 50 healthy subjects. Results showed a significant
      increase in plasma levels of VEGF (P < 0.001), PDGF (P < 0.001), TNF-alpha (P <
      0.01), angiostatin (P < 0.01), and IP-10 (P < 0.001) and a significant reduction
      in IL-12 (P < 0.001) in HCC patients in relation to normal controls. Classifying
      HCC patients based on their Child-Pugh's score revealed that the maximum
      production of proangiogenic mediators (VEGF and TNF-alpha) was present in HCC
      patients with Child-Pugh C score which coincides with maximum reduction in
      antiangiogenic mediators (IL-4, IL-12, and angiostatin). Taken together, these
      results indicated that the determination of these factors in different Child
      Pugh's scores of HCC might be an important guide in clinical decision making
      regarding therapy and outcome.

PMID- 24677136
TI  - Role of Fas and Treg cells in fracture healing as characterized in the fas
      deficient (lpr) mouse model of lupus.
AB  - Previous studies showed that loss of tumor necrosis factor alpha (TNFalpha)
      signaling delayed fracture healing by delaying chondrocyte apoptosis and
      cartilage resorption. Mechanistic studies showed that TNFalpha induced Fas
      expression within chondrocytes; however, the degree to which chondrocyte
      apoptosis is mediated by TNFalpha alone or dependent on the induction of Fas is
      unclear. This question was addressed by assessing fracture healing in Fas
      deficient B6.MRL/Fas(lpr) /J mice. Loss of Fas delayed cartilage resorption but
      also lowered bone fraction in the calluses. The reduced bone fraction was related
      to elevated rates of coupled bone turnover in the B6.MRL/Fas(lpr) /J calluses, as
      evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of
      the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts
      in calluses of B6.MRL/Fas(lpr) /J mice. To determine if an active autoimmune
      state contributed to increased bone turnover, the levels of activated T cells and
      Treg cells were assessed. B6.MRL/Fas(lpr) /J mice had elevated Treg cells in both
      spleens and bones of B6.MRL/Fas(lpr) /J but decreased percentage of activated T
      cells in bone tissues. Fracture led to ~30% to 60% systemic increase in Treg
      cells in both wild-type and B6.MRL/Fas(lpr) /J bone tissues during the period of
      cartilage formation and resorption but either decreased (wild type) or left
      unchanged (B6.MRL/Fas(lpr) /J) the numbers of activated T cells in bone. These
      results show that an active autoimmune state is inhibited during the period of
      cartilage resorption and suggest that iTreg cells play a functional role in this
      process. These data show that loss of Fas activity specifically in chondrocytes
      prolonged the life span of chondrocytes and that Fas synergized with TNFalpha
      signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically
      led to increased osteoclast numbers during later periods of fracture healing and
      increased osteogenesis. These findings suggest that retention of viable
      chondrocytes locally inhibits osteoclast activity or matrix proteolysis during
      cartilage resorption.

PMID- 24677138
TI  - Mode coupling points to functionally important residues in myosin II.
AB  - Relevance of mode coupling to energy/information transfer during protein
      function, particularly in the context of allosteric interactions is widely
      accepted. However, existing evidence in favor of this hypothesis comes
      essentially from model systems. We here report a novel formal analysis of the
      near-native dynamics of myosin II, which allows us to explore the impact of the
      interaction between possibly non-Gaussian vibrational modes on fluctutational
      dynamics. We show that an information-theoretic measure based on mode coupling
      alone yields a ranking of residues with a statistically significant bias favoring
      the functionally critical locations identified by experiments on myosin II.

PMID- 24677139
TI  - Integration of vestibular and gastrointestinal inputs by cerebellar fastigial
      nucleus neurons: multisensory influences on motion sickness.
AB  - Previous studies demonstrated that ingestion of the emetic compound copper
      sulfate (CuSO4) alters the responses to vestibular stimulation of a large
      fraction of neurons in brainstem regions that mediate nausea and vomiting,
      thereby affecting motion sickness susceptibility. Other studies suggested that
      the processing of vestibular inputs by cerebellar neurons plays a critical role
      in generating motion sickness and that neurons in the cerebellar fastigial
      nucleus receive visceral inputs. These findings raised the hypothesis that
      stimulation of gastrointestinal receptors by a nauseogenic compound affects the
      processing of labyrinthine signals by fastigial nucleus neurons. We tested this
      hypothesis in decerebrate cats by determining the effects of intragastric
      injection of CuSO4 on the responses of rostral fastigial nucleus to whole-body
      rotations that activate labyrinthine receptors. Responses to vestibular
      stimulation of fastigial nucleus neurons were more complex in decerebrate cats
      than reported previously in conscious felines. In particular, spatiotemporal
      convergence responses, which reflect the convergence of vestibular inputs with
      different spatial and temporal properties, were more common in decerebrate than
      in conscious felines. The firing rate of a small percentage of fastigial nucleus
      neurons (15%) was altered over 50% by the administration of CuSO4; the firing
      rate of the majority of these cells decreased. The responses to vestibular
      stimulation of a majority of these cells were attenuated after the compound was
      provided. Although these data support our hypothesis, the low fraction of
      fastigial nucleus neurons whose firing rate and responses to vestibular
      stimulation were affected by the administration of CuSO4 casts doubt on the
      notion that nauseogenic visceral inputs modulate motion sickness susceptibility
      principally through neural pathways that include the cerebellar fastigial
      nucleus. Instead, it appears that convergence of gastrointestinal and vestibular
      inputs occurs mainly in the brainstem.

PMID- 24677140
TI  - Does calculating impair postural stabilization allowed by visual cues?
AB  - In many daily situations, balance control is associated with a cognitive activity
      such as reading or a simple calculation. The objective of this study was to
      investigate the relationship between these two specific human activities,
      especially the influence of visual cues and support surface stability on body
      sway during a calculation task. A Sensory Organization Test, which can disrupt or
      suppress sensory inputs, was performed on 71 healthy young adults. The
      evaluations were performed both with and without mental arithmetic tasks which
      consisted of backward counting by three or thirteen. Our results showed that the
      addition of a calculation task induced an increase in body sway only when visual
      cues were available. They also showed the same instability effect of the support
      surface on the amount of body sway no matter what the associated cognitive task
      was. Moreover, no difference in body sway was observed between the two
      calculation tasks no matter what the visual context and/or the stability of the
      support surface were. We suggest that focusing on fulfilling the requirements of
      the mental calculation challenge may be responsible for the increase in body
      sway. This increase may be related to the use of oculomotor activity as
      unintentional attempts to increase arousal by self-generated body movement. Thus,
      this activity facilitates information processing rather than minimizing unbalance
      by a visual anchor point. 

PMID- 24677141
TI  - Effect of hepatic impairment on the pharmacokinetics of levomilnacipran following
      a single oral dose of a levomilnacipran extended-release capsule in human
      participants.
AB  - BACKGROUND AND OBJECTIVES: Levomilnacipran is a serotonin and norepinephrine
      reuptake inhibitor with greater potency for the reuptake inhibition of
      norepinephrine than of serotonin, approved in the USA for the treatment of major
      depressive disorder (MDD) in adults. METHODS: A single-dose, open-label, parallel
      group study was conducted to evaluate the effects of hepatic impairment on the
      pharmacokinetics of levomilnacipran in adults with mild, moderate, or severe
      hepatic impairment and normal controls receiving a 40 mg levomilnacipran extended
      release (ER) capsule. The concentrations of levomilnacipran and its inactive
      metabolite, N-desethyl levomilnacipran, in plasma and urine were measured using
      liquid chromatography-tandem mass spectrometry methods. Pharmacokinetic
      parameters of levomilnacipran and N-desethyl levomilnacipran were derived and
      assessed. Safety parameters were assessed throughout the trial. RESULTS: No
      deaths, serious adverse events, or discontinuations due to adverse events
      occurred. The maximum plasma drug concentration (C(max)) and area under the
      plasma concentration-time curve from time zero to infinity (AUC(infinity)) of
      levomilnacipran were 28 and 32 % higher, respectively, in participants with
      severe hepatic impairment than in healthy participants without a notable change
      in the terminal elimination half-life, whereas the C(max) and AUC(infinity) of N
      desethyl levomilnacipran were 66 and 85 % lower, respectively, suggesting liver
      function has minimal impact on the overall exposure of levomilnacipran but plays
      a significant role in the formation of the metabolite. CONCLUSIONS: A single dose
      of levomilnacipran ER 40 mg was generally well-tolerated in participants with
      varying degrees of hepatic impairment and healthy controls. Therefore, dose
      adjustment for levomilnacipran is not necessary in adult MDD patients with
      impaired liver function.

PMID- 24677142
TI  - Impaired verbal memory is a significant predictor of early cerebral
      cardiovascular death, an 18-year follow-up of a national cohort.
AB  - BACKGROUND: The mortality pattern of individuals with impaired verbal memory
      (IVM) has not yet been well described. We sought to describe the risk of all
      causes, as well as specific causes of death associated with IVM. METHOD: We used
      the data of 4151 nationally representative adults >=60 years old who participated
      in the third National Health and Nutrition Examination Survey, 1988-1994, and
      completed one non-contextual (i.e., word list memory) and one contextual delayed
      recall tests (i.e., short story recall). The participants were passively followed
      up through 31 December 2006. We determined the hazard ratio of death from all
      causes and specific cause through Cox proportional hazard regression. RESULTS:
      Severe and moderate IVM were present in 268 (6.5%) and 495 (11.9%) participants
      at baseline survey, and 2550 deaths occurred by the end of 18-year follow-up
      (median = 12 years). The medians of survival time adjusted for all-causes death
      were 6.17 (95% CI: 5.50, 6.92), 9.50 (8.92, 10.25), and 13.17 (12.75, 13.58)
      years, respectively for the individuals with severe, moderate, and no IVM. Severe
      IVM was significantly associated with death from cardio-cerebral vascular
      diseases [hazard ratio = 1.70, 95% CI = (1.36-2.12)], stroke [2.60 (1.69-3.99)],
      and Alzheimer's disease [3.50 (1.40-8.76)]. The shortened survival time of the
      participants with IVM was mainly driven by the deaths of cerebral-cardiovascular
      diseases, which accounted for almost half of all deaths. CONCLUSION: The
      predictability of memory scores to early cerebral-cardiovascular deaths
      demonstrated that central challenge among individuals with cognitive impairment
      was cardiovascular diseases management.

PMID- 24677143
TI  - Hymenobacter qilianensis sp. nov., isolated from a subsurface sandstone sediment
      in the permafrost region of Qilian Mountains, China and emended description of
      the genus Hymenobacter.
AB  - A red-pink, Gram-negative, rod-shaped, non-motile, non-spore-forming bacterium,
      designated strain DK6-37 was isolated from the permafrost region of Qilian
      Mountains in northwest of China. Phylogenetic analysis based on 16S rRNA gene
      sequencing indicated that this isolate represents a novel member of the genus
      Hymenobacter, with low sequence similarities (<97 %) to recognized Hymenobacter
      species. Optimum growth was observed at 28  degrees C, pH 7.0 and 0 % NaCl. The
      strain was found to contain MK-7 as the predominant menaquinone. The polar lipids
      were identified as phosphatidylethanolanmine, two unknown aminophospholipids, one
      unknown aminolipid and three unknown polar lipids. The major fatty acids were
      identified as summed feature 3 (C16:1 omega7c/C16:1 omega6c as defined by MIDI),
      summed feature 4 (anteiso-C17:1 B/iso-C17:1 I), C16:1 omega5c, iso-C17:0 3-OH,
      iso-C15:0 and C18:0. The DNA G + C content was determined to be 67.4 mol %. On
      the basis of the polyphasic evidence presented, it is proposed that strain DK6-37
      represents a novel species of the genus Hymenobacter, for which the name
      Hymenobacter qilianensis sp. nov. is proposed. The type strain is DK6-37(T) (=
      CGMCC 1.12720(T) = JCM 19763(T)). 

PMID- 24677144
TI  - Halapricum salinum gen. nov., sp. nov., an extremely halophilic archaeon isolated
      from non-purified solar salt.
AB  - A halophilic archaeal strain, designated CBA1105(T), was isolated from non
      purified solar salt. Strain CBA1105(T) was found to have three 16S rRNA genes,
      rrnA, rrnB and rrnC; similarities between the 16S rRNA gene sequences were 99.5
      99.7 %. The phylogenetic analysis of the 16S rRNA gene sequences showed that
      strain CBA1105(T) forms a distinct clade with the strains of the closely related
      genera, Halorientalis and Halorhabdus, with similarities of 94.2 % and 93.9-94.2
      %, respectively. Multilocus sequence analysis confirmed that strain CBA1105(T) is
      closely related to the genus Halorhabdus or Halorientalis. Growth of the strain
      was observed in 15-30 % NaCl (w/v; optimum 20 %), at 30-45  degrees C (optimum 37
      degrees C) and pH 7.0-8.0 (optimum pH 7.0) and with 0-0.5 M MgCl2.6H2O (optimum
      0.05-0.2 M). The cells of the strain were observed to be Gram-stain negative and
      pleomorphic with coccoid or ovoid-shape. The cells lysed in distilled water.
      Tweens 20, 40 and 80 were found to be hydrolysed but starch, casein and gelatine
      were not. The cells were unable to reduce nitrate under aerobic conditions.
      Assays for indole formation and urease activity were negative and no growth was
      observed under anaerobic conditions. Cells were found to be able to utilize L
      glutamate, D-glucose, L-maltose, D-mannose and sucrose as sole carbon sources.
      The polar lipids were identified as phosphatidylglycerol, phosphatidylglycerol
      phosphate methyl ester, unidentified glycolipids and an unidentified
      phospholipid. The G+C content of strain CBA1105(T) was determined to be 66.0
      mol%. The phenotypic, chemotaxonomic and phylogenetic properties suggest that the
      strain represents a novel species of a novel genus within the family
      Halobacteriaceae, for which the name Halapricum salinum is proposed with
      CBA1105(T) (= KCTC 4202(T) = JCM 19729(T)) as the type strain. 

PMID- 24677145
TI  - Properties of individual dopant atoms in single-layer MoS2: atomic structure,
      migration, and enhanced reactivity.
AB  - Single-layered MoS2 doped with Re (n-type) and Au (p-type) are investigated by in
      situ scanning transmission electron microscopy. Re atoms substituting Mo sites
      enhance the local chemical affinity, evidenced by agglomeration of other
      dopant/impurity atoms. Au atoms exist as adatoms and show larger mobility under
      the electron beam. These behaviors are consistent with density functional theory
      calculations. 

PMID- 24677146
TI  - Novel femoral artery terminology: integrating anatomy and clinical procedures
      leading to standardized intuitive nomenclature.
AB  - The objective of this study is to investigate the terminology of the femoral
      artery and recommended alternative terminology that satisfies both anatomy and
      clinical arenas.The femoral artery (FA) is often defined as the continuation of
      the external iliac artery. Specifically, when the external iliac artery reaches
      directly beneath the inguinal ligament, it becomes the FA. Currently,
      Terminologia Anatomica (TA) records the profunda femoris or deep femoral as a
      terminal branch. Clinicians often use superficial femoral artery (SFA) rather
      than FA and profunda or deep FA. SFA is actually very deep and well protected for
      most of its journey. On observation, the terminology in current use is not
      intuitive. The objective of this study was to investigate the terminology
      associated with the anatomical and clinical anatomical interpretations of the FA
      and its terminal branches and to suggest a more appropriate terminology that
      addresses the points of view of the macro anatomist, as well as that of the
      clinician. Literature search was conducted regarding the nomenclature of the FA
      and its terminal branches. Dissection of 89 embalmed cadavers (49F, 40M, ages 47
      89) was conducted to analyze the morphology of the FA and its branches. Perusal
      of the literature revealed a difference in terminology between anatomical and
      clinical textbooks/atlases/journals regarding the FA and its terminal branch. Our
      dissections suggested that the FA may be better defined vis-a-vis its
      relationship to the anterior and posterior compartments of the thigh. A
      difference in terminology exists between the anatomical and clinical arenas. A
      need for a standardized terminology is necessary because clinicians and their
      publishers have not adopted TA. This study suggests that the current FA be
      considered the common FA and the continuation of the FA, the SFA be renamed the
      anterior FA and the current profunda (the deep FA) be renamed the posterior FA,
      respectively. The proposed terminology mirrors the lower limb anterior/posterior
      tibial artery terminology.

PMID- 24677147
TI  - Minimally invasive endogastric removal of migrated gastric band after endoscopic
      failure: how I do it.
AB  - Intragastric band migration is a rare and late complication of laparoscopic 
      adjustable gastric banding and should be recognized by all digestive surgeons.
      Endoscopic removal is most commonly performed, but surgery is an alternative in
      cases of endoscopic failure. Many different procedures have been reported. We
      show here (see Video) a fully laparoscopic endogastric procedure through two 5-mm
      antral gastrotomies. This technique can also be used to remove benign endogastric
      tumors. The procedure is safe and provides a large endogastric operative area,
      with no particular morbidity. Endogastric removal through a fully laparoscopic
      approach should be considered as the first alternative to endoscopic approach. 

PMID- 24677148
TI  - Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical
      prevention of breast cancer-related lymphedema: over 4 years follow-up.
AB  - Breast cancer-related lymphedema (LE) represents an important morbidity that
      jeopardizes breast cancer patients' quality of life. Different attempts to
      prevent LE brought about improvements in the incidence of the pathology but LE
      still represents a frequent occurrence in breast cancer survivors. Over 4 years
      ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed
      and long-term results are reported in this study. From July 2008 to December
      2012, 74 patients underwent axillary nodal dissection for breast cancer treatment
      together with LYMPHA procedure. Volumetry was performed preoperatively in all
      patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was
      performed in 45 patients preoperatively and in 30 also postoperatively after at
      least over 1 year. Seventy one patients had no sign of LE, and volumetry was
      coincident to preoperative condition. In three patients, LE occurred after 8-12
      months postoperatively. Lymphoscintigraphy showed the patency of lymphatic-venous
      anastomoses at 1-4 years after operation. LYMPHA technique represents a
      successful surgical procedure for primary prevention of arm LE in breast cancer
      patients.

PMID- 24677149
TI  - Taurine promotes human mesenchymal stem cells to differentiate into osteoblast
      through the ERK pathway.
AB  - Taurine has been reported to influence bone metabolism, but the role of taurine
      on osteogenic differentiation of human mesenchymal stem cells (hMSCs) remains
      unclear. In the present study, we investigated the effect of taurine on
      osteogenic differentiation of hMSCs. The results showed that taurine increased
      the alkaline phosphatase (ALP) activity and mineralized nodules in hMSCs induced
      by osteogenic induced medium. Meanwhile, RT-PCR analysis showed that taurine up
      regulated the mRNA expression of ALP, osteopontin, Runt-related transcription
      factor 2 (Runx2) and Osterix in a dose-dependent manner. Furthermore, taurine
      induced activation of extracellular signal regulated kinase (ERK) and
      pretreatment with the ERK inhibitor U0126 abolished the taurine-induced
      osteogenesis of hMSCs. Taken together, our study reveals that taurine promotes
      the osteogenesis of hMSCs by activating the ERK pathway.

PMID- 24677150
TI  - Anomalies and specific functions in the clinical identification of defense
      mechanisms.
AB  - Standard teaching about defense mechanisms generally focuses on definitions,
      which do not readily aid the clinician in identifying defenses whenever
      individuals use them. This report demonstrates a process by which the clinician
      can identify when a defense is used, which ones are likely being used, and with
      what aim. Clinicians first notice that a defense may be operating whenever the
      other individual presents with anomalies in the expression of affect, behavior,
      speech, or its content. Some of these anomalies are described. Next, to identify
      the specific defense or general level of defensive functioning used, the
      clinician must identify the specific function of the defense in context using a
      process of guided clinical inference. This report examines 2 verbatim examples
      from recorded interviews of one case to demonstrate this process. The examples
      present a microcosm of clinical concerns that have a surprising relationship to
      the individual's course and prognosis.

PMID- 24677151
TI  - Cerebral networks of sustained attention and working memory: a functional
      magnetic resonance imaging study based on the Continuous Performance Test.
AB  - INTRODUCTION: One of the most used paradigms in the study of attention is the
      Continuous Performance Test (CPT). The identical pairs version (CPT-IP) has been
      widely used to evaluate attention deficits in developmental, neurological and
      psychiatric disorders. However, the specific locations and the relative
      distribution of brain activation in networks identified with functional imaging,
      varies significantly with differences in task design. AIM: To design a task to
      evaluate sustained attention using functional magnetic resonance imaging (fMRI),
      and thus to provide data for research concerned with the role of these functions.
      SUBJECTS AND METHODS: Forty right-handed, healthy students (50% women; age range:
      18-25 years) were recruited. A CPT-IP implemented as a block design was used to
      assess sustained attention during the fMRI session. RESULTS: The behavioural
      results from the CPT-IP task showed a good performance in all subjects, higher
      than 80% of hits. fMRI results showed that the used CPT-IP task activates a
      network of frontal, parietal and occipital areas, and that these are related to
      executive and attentional functions. CONCLUSIONS: In relation to the use of the
      CPT to study of attention and working memory, this task provides normative data
      in healthy adults, and it could be useful to evaluate disorders which have
      attentional and working memory deficits.

PMID- 24677152
TI  - [Predictors of the recovery of cognitive functions in patients with traumatic
      brain injury].
AB  - INTRODUCTION: After a traumatic brain injury (TBI), cognitive functionality may
      be severely altered. Some studies have aimed at identifying the best predictive
      variables for cognitive recovery, however, results still remain unclear. AIMS: To
      assess the recovery of cognitive functionality in TBI patients after a
      rehabilitation programme, and to identify the variables that best predict the
      cognitive recovery. PATIENTS AND METHODS: We conducted a retrospective pre-post
      study with 58 adult TBI patients that underwent an intensive rehabilitation
      programme. All of them were assessed using the cognitive functions sub-scale from
      the FIM+FAM scale, at admission and discharge. Both scores were compared using
      non-parametric test Wilcoxon. Cognitive functionality gain percentage was
      calculated and correlated with all the collected data. A multiple linear
      regression analysis was carried out to identify the best predictors of cognitive
      functionality gain percentage by introducing all clinical, demographic and
      cognitive information. RESULTS: The group's cognitive functionality increased
      significantly from 33,6% to 85% (p < 0,01). Patients with higher cognitive
      functionality gain percentage were those with younger age, shorter time post-TBI,
      and higher scores on cognitive functions sub-scale, conditional attention and
      Luria's memory word tests. The best predictors for cognitive functionality gain
      percentage were time post-TBI and cognitive functions at admission (adjusted R(2)
      = 55,8%). CONCLUSIONS: Patients who started rehabilitation sooner and had a
      higher cognitive functionality at admission, showed the greatest increase in
      cognitive functionality gain percentage. Other variables like age, or scores on
      cognitive tests must also be considered in future studies.

PMID- 24677153
TI  - [Gorlin syndrome in the paediatric age].
AB  - INTRODUCTION: Gorlin syndrome (GS) is a disorder transmitted by dominant
      autosomal inheritance associated to mutations in PTCH1, the main characteristic
      of which is the appearance of basal cell carcinomas, together with skeletal
      abnormalities, odontogenic keratocysts and intracranial tumours. CASE REPORT: A
      girl aged 3 years and 10 months, who was admitted due to acute ataxia. Some of
      the more striking features in the patient's personal history include psychomotor
      retardation and a family history of suspected GS in the mother as a result of a
      maxillary cyst. An examination revealed macrocephaly with a prominent forehead
      and hypertelorism, as well as nevus. A genetic study for GS was requested, in
      which mutation c.930delC was detected in exon 6 of the PTCH1 gene in
      heterozygosis. CONCLUSIONS: In GS there is an increase in the likelihood of
      developing basal cell carcinomas and strict dermatological monitoring is
      necessary. A clinical neurological follow-up and also magnetic resonance imaging
      scans are needed for an early diagnosis of intracranial tumours, especially in
      the case of medulloblastomas. Odontogenic keratocysts, other skin disorders, and
      cardiac and ovarian fibromas are characteristic, as are skeletal abnormalities,
      which require regular clinical and neuroimaging controls and treatment if needed,
      but radiation must be avoided. GS is a rare disorder, but it must be suspected in
      the presence of characteristic alterations. It requires a multidisciplinary
      follow-up, and it is also necessary to establish a protocol on how to act so as
      to allow early diagnosis and treatment of the potentially severe complications
      deriving from this disease.

PMID- 24677154
TI  - [Biomarkers in Alzheimer's disease].
AB  - The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging
      and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the
      certainty of whether a patient has an ongoing AD neuropathologic process or not.
      Three CSF biomarkers, Abeta42, total tau, and phosphorylated tau, reflect the
      core pathological features of AD. It is already known that these pathological
      processes of AD starts decades before the first symptoms, so these biomarkers may
      provide means of early disease detection. At least three stages of AD could be
      identified: preclinical AD, mild cognitive impairment due to AD, and dementia due
      to AD. In this review, we aim to summarize the CSF biomarker data available for
      each of these stages. We also review the actual research on blood-based
      biomarkers. Recent studies on healthy elderly subjects and on carriers of
      dominantly inherited AD mutations have also found biomarker changes that allow
      separate groups in these preclinical stages. These studies may aid for segregate
      populations in clinical trials and objectively evaluate if there are changes over
      the pathological processes of AD. Limits to widespread use of CSF biomarkers,
      apart from the invasive nature of the process itself, is the higher coefficient
      of variation for the analyses between centres. It requires strict pre-analytical
      and analytical procedures that may make feasible multi-centre studies and global
      cut-off points for the different stages of AD. 

PMID- 24677155
TI  - [Functional magnetic resonance imaging: a critical analysis of its technical,
      statistical and theoretical implications in human neuroscience].
AB  - INTRODUCTION: The use of functional magnetic resonance imaging (fMRI) has
      represented an important step forward for the neurosciences. Nevertheless, it has
      also been subject to rather a lot of criticism. AIM: To study the most widespread
      criticism against fMRI, so that researchers who are starting to use it may know
      the different elements that must be taken into account to be able to take a
      suitable approach to this technique. DEVELOPMENT: The fact that fMRI allows brain
      activity to be observed makes it a very attractive and useful tool, and its use
      has grown exponentially since the last decade of the 20th century. At the same
      time, criticism against its use has become especially fierce. Most of this
      scepticism can be classified into aspects related with the technique and
      physiology, the analysis of data and their theoretical interpretation. In this
      study we will review the main arguments defended in each of these three areas, as
      well as looking at whether they are well-founded or not. Additionally, this work
      is also intended as a reference for novel researchers when it comes to
      identifying elements that must be taken into account as they approach fMRI.
      CONCLUSIONS: Despite the fact that fMRI is one of the most interesting options
      for observing the brain available today, its correct utilisation requires a great
      deal of control and knowledge. Even so, today most of the criticism it receives
      no longer has any solid foundation on which to stand.

PMID- 24677157
TI  - [Flax-leaved daphne (Daphne gnidium L.): an ancient European timbo].

PMID- 24677158
TI  - Usefulness of optical coherence tomography to detect central serous
      chorioretinopathy in monkeys.
AB  - Many systemic drugs can induce ocular toxicity and several ocular side-effects
      have been identified in clinical studies. However, it is difficult to detect
      ocular toxicity in preclinical studies because of the lack of appropriate
      evaluation methods. Optical coherence tomography (OCT) is useful because it can
      provide real-time images throughout a study period, whereas histopathology only
      provides images of sacrificed animals. Using OCT alongside histopathology,
      attempts were made to find effective approaches for screening of drug-induced
      ocular toxicity in monkeys. Such approaches could be used in preclinical studies
      prior to human trials. Six male cynomolgus monkeys (Macaca fascicularis Raffles)
      were orally administered one of six candidate MAPK/ERK kinase (MEK) inhibitors.
      Central serous chorioretinopathy, a known side-effect of such inhibitors, was
      identified in four monkeys by OCT. Artifacts generated during tissue processing
      meant that histopathology could not detect edematous changes. Thus, OCT is a
      useful tool to detect ocular toxicity which cannot be detected by histopathology
      in preclinical studies.

PMID- 24677159
TI  - Staphylococcus aureus bacteraemia in a UK tertiary referral centre: a
      'transoesophageal echocardiogram for all' policy.
AB  - OBJECTIVES: Infective endocarditis (IE) is a feared complication in up to 38% of
      cases of Staphylococcus aureus bacteraemia (SAB). BSAC guidelines recommend
      echocardiography in all cases of SAB. The aim of this study was to determine the
      incidence of IE in SAB using transoesophageal echocardiography (TOE) as the first
      step in diagnostic imaging. This study also sought to identify clinical
      predictors that could improve stratification of those with and without IE.
      METHODS: A guideline was implemented that any SAB resulted in the microbiology
      department (i) recommending that the patient be referred for TOE and (ii)
      notifying the echocardiography department, resulting in streamlined listing of
      the patient for TOE. All cases of SAB were then assessed prospectively at
      University Hospitals Birmingham NHS Foundation Trust between September 2011 and
      October 2012. Previously identified risk factors for complicated S. aureus
      bacteraemia were recorded. RESULTS: There were 98 SAB episodes in total. TOE was
      performed in 58 (59%) with a further 22 episodes imaged by transthoracic
      echocardiography alone. IE was diagnosed overall in 13 (16%) cases investigated
      with echocardiography. No risk factor for IE other than presence of a cardiac
      device was detected in this group (P = 0.013). CONCLUSIONS: The rate of IE found
      in SAB is high when TOE is performed first line. There are no clear risk factors
      to improve yield or the type of echocardiography to be performed.
      Echocardiography should be performed in all cases and TOE should be considered
      where it is expected to influence management, as long as local resources allow.

PMID- 24677160
TI  - Rapid nucleic acid diagnostics for the detection of antimicrobial resistance in
      Gram-negative bacteria: is it time for a paradigm shift?
AB  - A key component for tackling the ever more serious antimicrobial resistance
      problem in Gram-negative bacteria is the introduction of rapid nucleic acid
      diagnostics. Successful incorporation of new diagnostic technologies has the
      potential benefit of improving not only patient treatment but also infection
      control and antimicrobial stewardship. However, there are still many hurdles to
      overcome, such as the complexity of resistance mechanisms in Gram-negative
      bacteria, the discrepancy between phenotype and genotype and the difficulty in
      distinguishing pathogens from background commensals. A small number of
      manufacturers have introduced tests to the market that concentrate partly or
      specifically on resistance determinants in Gram-negative bacteria. These are
      currently predominantly based on different types of PCR technology. The
      development of new technologies, such as whole-genome sequencing and the
      combination of MALDI-TOF with PCR, holds much promise for the introduction of
      improved diagnostics for the future. 

PMID- 24677161
TI  - Integrated metabolic spatial-temporal model for the prediction of ammonia
      detoxification during liver damage and regeneration.
AB  - The impairment of hepatic metabolism due to liver injury has high systemic
      relevance. However, it is difficult to calculate the impairment of metabolic
      capacity from a specific pattern of liver damage with conventional techniques. We
      established an integrated metabolic spatial-temporal model (IM) using hepatic
      ammonia detoxification as a paradigm. First, a metabolic model (MM) based on mass
      balancing and mouse liver perfusion data was established to describe ammonia
      detoxification and its zonation. Next, the MM was combined with a spatial
      temporal model simulating liver tissue damage and regeneration after CCl4
      intoxication. The resulting IM simulated and visualized whether, where, and to
      what extent liver damage compromised ammonia detoxification. It allowed us to
      enter the extent and spatial patterns of liver damage and then calculate the
      outflow concentrations of ammonia, glutamine, and urea in the hepatic vein. The
      model was validated through comparisons with (1) published data for isolated,
      perfused livers with and without CCl4 intoxication and (2) a set of in vivo
      experiments. Using the experimentally determined portal concentrations of
      ammonia, the model adequately predicted metabolite concentrations over time in
      the hepatic vein during toxin-induced liver damage and regeneration in rodents.
      Further simulations, especially in combination with a simplified model of blood
      circulation with three ammonia-detoxifying compartments, indicated a yet
      unidentified process of ammonia consumption during liver regeneration and
      revealed unexpected concomitant changes in amino acid metabolism in the liver and
      at extrahepatic sites. CONCLUSION: The IM of hepatic ammonia detoxification
      considerably improves our understanding of the metabolic impact of liver disease
      and highlights the importance of integrated modeling approaches on the way toward
      virtual organisms.

PMID- 24677163
TI  - Perceived discrimination and medication adherence in black hypertensive patients:
      the role of stress and depression.
AB  - OBJECTIVE: To examine the relationship between perceived discrimination and
      medication adherence among black people with hypertension and the role of stress
      and depressive symptoms in this relationship. Perceived racial discrimination has
      been associated with poor health outcomes in blacks; its relationship to
      medication adherence among hypertensive patients remains untested. METHODS: We
      measured perceived racial discrimination at baseline, stress and depressive
      symptoms at 6 months, and medication adherence at 12 months among patients
      enrolled in a 30-site cluster-randomized controlled trial testing a patient and
      physician-targeted intervention to improve blood pressure. A mediational method
      with bootstrapping (stratified by site) confidence intervals was used to estimate
      the indirect association between perceived discrimination and medication
      adherence through stress and depression. RESULTS: Of 1056 patients from 30 sites
      enrolled in the trial, 463 had complete data on all four measures at 6 and 12
      months and were included in the analyses. Adjusting for clustering, perceived
      discrimination was associated with poor medication adherence (B = 0.138, p =
      .011) at 12 months, and with stress (B = 2.24, p = .001) and depression (B =
      1.47, p = .001) at 6 months. When stress and depression were included in the
      model, there was a 65% reduction in the total association of perceived
      discrimination with medication adherence, and the relationship was no longer
      significant (B = 0.049, p = .35). CONCLUSIONS: Perceived discrimination is
      associated with poor medication adherence among hypertensive blacks, and stress
      and depressive symptoms may account for this relationship. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00233220.

PMID- 24677162
TI  - Retinal ganglion cell topography and spatial resolution of two parrot species:
      budgerigar (Melopsittacus undulatus) and Bourke's parrot (Neopsephotus bourkii).
AB  - Retinal ganglion cell (RGC) isodensity maps indicate important regions in an
      animal's visual field. These maps can also be combined with measures of focal
      length to estimate the theoretical visual acuity. Here we present the RGC
      isodensity maps and anatomical spatial resolving power in three budgerigars
      (Melopsittacus undulatus) and two Bourke's parrots (Neopsephotus bourkii).
      Because RGCs were stacked in several layers, we modified the Nissl staining
      procedure to assess the cell number in the whole-mounted and cross-sectioned
      tissue of the same retinal specimen. The retinal topography showed surprising
      variation; however, both parrot species had an area centralis without discernable
      fovea. Budgerigars also had a putative area nasalis never reported in birds
      before. The peak RGC density was 22,300-34,200 cells/mm(2) in budgerigars and
      18,100-38,000 cells/mm(2) in Bourke's parrots. The maximum visual acuity based on
      RGCs and focal length was 6.9 cyc/deg in budgerigars and 9.2 cyc/deg in Bourke's
      parrots. These results are lower than earlier behavioural estimates. Our findings
      illustrate that retinal topography is not a very fixed trait and that theoretical
      visual acuity estimations based on RGC density can be lower than the behavioural
      performance of the bird.

PMID- 24677164
TI  - Inequalities in lung cancer care of elderly patients with schizophrenia: an
      observational cohort study.
AB  - OBJECTIVE: Cancer mortality is higher in individuals with schizophrenia, a
      finding that may be due, in part, to inequalities in care. We evaluated gaps in
      lung cancer diagnosis, treatment, and survival among elderly individuals with
      schizophrenia. METHODS: The Surveillance, Epidemiology, and End Results database
      linked to Medicare records was used to identify patients 66 years or older with
      primary non-small cell lung cancer. Lung cancer stage, diagnostic evaluation, and
      rates of stage-appropriate treatment were compared among patients with and
      without schizophrenia using unadjusted and multiple regression analyses. Survival
      was compared among groups using Kaplan-Meier methods. RESULTS: Of the 96,702
      patients with non-small cell lung cancer in the Surveillance, Epidemiology, and
      End Results database, 1303 (1.3%) had schizophrenia. In comparison with the
      general population, patients with schizophrenia were less likely to present with
      late-stage disease after controlling for age, sex, marital status,
      race/ethnicity, income, histology, and comorbidities (odds ratio = 0.82, 95%
      confidence interval = 0.73-0.93) and were less likely to undergo appropriate
      evaluation (p < .050 for all comparisons). Adjusting for similar factors,
      patients with schizophrenia were also less likely to receive stage-appropriate
      treatment (odds ratio = 0.50, 95% confidence interval = 0.43-0.58). Survival was
      decreased among patients with schizophrenia (mean survival = 22.3 versus 26.3
      months, p = .002); however, no differences were observed after controlling for
      treatment received (p = .40). CONCLUSIONS: Elderly patients with schizophrenia
      present with earlier stages of lung cancer but are less likely to undergo
      diagnostic evaluation or to receive stage-appropriate treatment, resulting in
      poorer outcomes. Efforts to increase treatment rates for elderly patients with
      schizophrenia may lead to improved survival in this group.

PMID- 24677165
TI  - Current perspective on mental stress-induced myocardial ischemia.
AB  - Mental stress and emotional arousal can act as triggers of myocardial infarction
      and other adverse cardiovascular outcomes. This editorial presents an overview of
      the research on mental stress-induced myocardial ischemia (MSIMI) and comments on
      two investigations examining MSIMI published in this journal. These studies
      confirm that MSIMI is frequently observed in patients with coronary artery
      disease and that characteristics, such as being a woman younger than 50 years and
      depression, may increase the relative risk of MSIMI. The method used for
      determining MSIMI (i.e., assessing cardiac function as determined by
      echocardiography versus measurement of myocardial perfusion using single-photon
      emission computed tomography), as well as the nature of the mental stress
      protocols (i.e., one stress task versus several repeated tasks), may have
      important effects on the findings of MSIMI research and on their interpretation.
      An overview of clinical characteristics of MSIMI is presented, and the article
      concludes with possible directions for future MSIMI research. 

PMID- 24677167
TI  - C(sp(2))-coupled nitronyl nitroxide and iminonitroxide diradicals.
AB  - Spin-labelled compounds are widely used in chemistry, physics, biology and the
      materials sciences but the synthesis of stable high-spin organic molecules is
      still a challenge. We succeeded in synthesising heteroatom analogues of the
      1,1,2,3,3-pentamethylenepropane (PMP) diradicals with two nitronyl nitroxide
      (DR1) and with two iminonitroxide (DR2) fragments linked through the C(sp2) atom
      of the nitrone group. According to magnetic susceptibility measurements, EPR data
      and ab initio calculations at the (8,6)CASSCF and (8,6)NEVPT2 levels, DR1 and DR2
      have singlet ground states. The singlet-triplet energy splitting (2J) is low
      (J/k=-7.4 for DR1 and -6.0 K for DR2), which comes from the disjoint nature of
      these diradicals. The reaction of [Cu(hfac)2] with DR1 gives rise to different
      heterospin complexes in which the diradical acts as a rigid ligand, retaining its
      initial conformation. For the [{Cu(hfac)2}2(DR1)(H2O)] complex, sufficiently
      strong ferromagnetic interactions (J1/k=42.7 and J2/k=14.1 K) between two
      coordinating CuII ions and DR1 were revealed. In
      [{Cu(hfac)2}2(DR1)(H2O)][Cu(hfac)2(H2O)], the very strong and antiferromagnetic
      (J/k=-416.1 K) exchange interaction between one of the coordinating CuII ions and
      DR1 is caused by the very short equatorial CuO bond length (1.962 A).

PMID- 24677166
TI  - MiR-101 suppresses the epithelial-to-mesenchymal transition by targeting ZEB1 and
      ZEB2 in ovarian carcinoma.
AB  - Ovarian carcinoma is the most lethal gynecologic malignancy; the majority of
      patients succumb to the disease within 5 years of diagnosis. The poor survival
      rate is attributed to diagnosis at advanced stage, when the tumor has
      metastasized. The epithelial-to-mesenchymal transition (EMT) is a necessary step
      toward metastatic tumor progression. Through integrated computational analysis,
      we recently identified a master microRNA (miRNA) network that includes miR-101
      and regulates EMT in ovarian carcinoma. In the present study, we characterized
      the functions of miR-101. Using reporter gene assays, we demonstrated that miR
      101 suppressed the expression of the E-cadherin repressors ZEB1 and ZEB2 by
      directly targeting the 3'-untranslated region (3'UTR) of both ZEB1 and ZEB2.
      Introduction of miR-101 significantly inhibited EMT and cell migration and
      invasion. Introducing cDNAs of ZEB1 and ZEB2 without 3'UTR abrogated miR-101
      induced EMT alteration, respectively. Our findings showed that miR-101 represents
      a redundant mechanism for the miR-200 family that regulates EMT through two major
      E-cadherin transcriptional repressors.

PMID- 24677168
TI  - Reply: To PMID 23519786.

PMID- 24677169
TI  - Predictors of excess mortality after fracture: a population-based cohort study.
AB  - To determine the extent to which excess mortality after fractures attributable to
      particular causes at specific skeletal sites can be predicted using data about
      all medical diagnoses, we conducted a historical cohort study among 1991 Olmsted
      County, Minnesota, residents aged >= 50 years who experienced any fracture in
      1989 to 1991 and who were followed passively for up to 22 years for death from
      any cause. We used a machine learning approach, gradient boosting machine (GBM)
      modeling, to determine whether the comorbid conditions present at the time of
      fracture and those that arose subsequently could, in aggregate, identify patients
      at the greatest increased risk of death. During 21,867 person-years of follow-up,
      1245 deaths were observed when 1061 were expected (standardized mortality ratio,
      1.2; 95% confidence interval [CI] 1.1-1.2). Patients presented with a median
      history of 26 comorbid conditions each as assessed by the Clinical Classification
      Software system and 57 each over the total duration of follow-up. Using all
      available information, the excess deaths could be predicted with good accuracy (c
      index >= 0.80) in 89% of the GBM models built for patients with different types
      of fracture; in one-third of the models, the c-index was >= 0.90. The conditions
      most prominent in the GBM prediction models were also reflected in the specific
      causes of death that were elevated, suggesting the influence of confounding on
      the relationship. However, the predominant comorbid conditions were mainly those
      responsible for mortality in the general population, rather than the specific
      diseases most closely associated with secondary osteoporosis. To reduce long-term
      deaths in the fracture population as a whole, a more general approach to the
      fracture patient is indicated.

PMID- 24677170
TI  - Supplementary sampling of obturation materials enhances microbial analysis of
      endodontic treatment failures: a proof of principle study.
AB  - OBJECTIVES: Root canal treatment failures often correlate with persistent
      biomaterial-associated endodontic infections. The aim of the present study was to
      assess the impact of endodontic obturation material sampling from root canals
      with posttreatment apical periodontitis on improving standard study protocols.
      MATERIALS AND METHODS: Samples from previously filled root canals and their
      corresponding endodontic filling materials were obtained from five root-filled
      teeth with posttreatment periradicular lesions. After cultivation, the isolated
      microorganisms were quantified and biochemically identified. Moreover, clone
      libraries were constructed after the amplification of bacterial 16S ribosomal DNA
      (rDNA) from the same samples. DNA from selected clones was sequenced to identify
      microbial species. Transmission electron microscopy (TEM) aided visualization of
      the detected bacteria. RESULTS: Overall, 22 taxa of the phyla Firmicutes,
      Actinobacteria, and Bacteroidetes were detected in both obturation and root canal
      samples by culture-dependent and culture-independent methods. Root canal fillings
      sheltered 17 species (3.30-7.50 * 10(3) CFU/ml). Of these, nine were detected
      solely in the retrieved obturation materials. The reinfected root canals harbored
      13 taxa (3.48-7.36 * 10(3) CFU/ml). Obligate and facultative anaerobic bacteria
      prevailed. The number of different species ranged from 1 to 5 within a single
      sample. Fungi were not detected. CONCLUSIONS: Bacteria can colonize both root
      canals and endodontic fillings in vivo. CLINICAL RELEVANCE: Integrating the
      sampling of obturation materials with standard root canal sample collection
      offers a clearer insight into the actual microbial flora of reinfected root
      canals and improves the study protocols of secondary/persistent endodontic
      infections.

PMID- 24677172
TI  - Out-of-home placement decision-making and outcomes in child welfare: a
      longitudinal study.
AB  - After children enter the child welfare system, subsequent out-of-home placement
      decisions and their impact on children's well-being are complex and under
      researched. This study examined two placement decision-making models: a
      multidisciplinary team approach, and a decision support algorithm using a
      standardized assessment. Based on 3,911 placement records in the Illinois child
      welfare system over 4 years, concordant (agreement) and discordant (disagreement)
      decisions between the two models were compared. Concordant decisions consistently
      predicted improvement in children's well-being regardless of placement type.
      Discordant decisions showed greater variability. In general, placing children in
      settings less restrictive than the algorithm suggested ("under-placing") was
      associated with less severe baseline functioning but also less improvement over
      time than placing children according to the algorithm. "Over-placing" children in
      settings more restrictive than the algorithm recommended was associated with more
      severe baseline functioning but fewer significant results in rate of improvement
      than predicted by concordant decisions. The importance of placement decision
      making on policy, restrictiveness of placement, and delivery of treatments and
      services in child welfare are discussed. 

PMID- 24677171
TI  - Salivary DNA and markers of oxidative stress in patients with chronic
      periodontitis.
AB  - OBJECTIVES: Previous observational studies have shown that periodontal status is
      associated with salivary markers of oxidative damage. A direct comparison of
      periodontitis patients and controls using a wide palette of salivary markers of
      oxidative stress is lacking. Characteristics of salivary DNA in periodontitis are
      unknown. The aim of this study was to compare the salivary markers of oxidative
      stress and characteristics of salivary DNA between patients with chronic
      periodontitis and periodontitis-free controls. MATERIALS AND METHODS: Saliva was
      collected from 23 patients with chronic periodontitis and 19 periodontitis-free
      controls. All participants underwent a clinical periodontal examination. Markers
      of oxidative and carbonyl stress were measured in saliva. Human and bacterial DNA
      was quantified, and human DNA integrity was assessed. RESULTS: Salivary
      thiobarbituric acid-reacting substances were higher in patients than in controls;
      at least in men, the difference was significant (p < 0.01). In women, patients
      had significantly lower salivary antioxidant status (p < 0.001). No quantitative
      differences were found regarding salivary DNA. Tendencies towards reduced DNA
      integrity were found in periodontitis patients. CONCLUSIONS: The results
      confirmed the association of salivary thiobarbituric acid-reacting substances
      with periodontitis. Lipid peroxidation in periodontitis seems to be caused by
      increased production of reactive oxygen species in men and by decreased
      antioxidant status in women. Whether lower salivary DNA integrity is involved in
      the pathogenesis of periodontitis remains to be elucidated. CLINICAL RELEVANCE:
      Salivary thiobarbituric acid-reacting substances are associated with
      periodontitis at least on a population level. Sex-specific causes of lipid
      peroxidation might point towards different pathogenic mechanisms.

PMID- 24677173
TI  - Clinical approaches to somatization.
AB  - Somatization is the experience and expression of psychological distress through
      bodily symptoms. Somatization can be conceptualized as an emotional state that
      has not been represented symbolically or as a defense against intolerable
      emotions and fantasies. Bodily concerns can also function as a means of seeking
      responsiveness from others. Alexithymia refers to a difficulty identifying and
      symbolizing emotional states that has been found to be associated with
      somatization. When functioning as a defense, a focus on the body can be used to
      avoid frightening or intolerable feelings and fantasies, or to ward off
      aggressive fantasies by viewing oneself as physically damaged. Systematic studies
      have demonstrated the presence of the defense of somatization in mood disorders,
      particularly anxiety and panic disorders. In treating anxiety disorders, the
      therapist helps the patient to determine the nature of emotions and fantasies
      that the patient is defending against, particularly fears and conflicts
      surrounding anger and separation.

PMID- 24677174
TI  - Graphene nanoplatelets doped with N at its edges as metal-free cathodes for
      organic dye-sensitized solar cells.
AB  - Challenging precious Pt-based electrocatalysts for dye-sensitized solar cells
      (DSSCs), graphene nanoplatelets that are N-doped at the edges (NGnPs) are
      prepared via simply ball-milling graphite in the presence of nitrogen gas. DSSCs
      based on specific nanoplatelets designated "NGnP5" display superior photovoltaic
      performance (power conversion efficiency, 10.27%) compared to that of
      conventional Pt-based devices (9.96%). More importantly, the NGnP counter
      electrode exhibits outstanding electrochemical stability and electrocatalytic
      activity with a cobalt-complex redox couple. 

PMID- 24677175
TI  - Shifting networks to achieve subgroup symmetry properties.
AB  - A simple method for the preparation of nanomaterials with new functionality by
      physical displacement of a network phase is suggested, giving a change in space
      group symmetry and hence properties. A double gyroid structure made by the self
      assembly of block copolymers is used as a model system for the demonstration of
      shifting networks to achieve single gyroid-like scattering properties. Free
      standing single gyroid-like network materials can be fabricated to give
      nanophotonic properties, similar to the photonic properties of a butterfly wing
      structure. 

PMID- 24677176
TI  - BetaVoid: molecular voids via beta-complexes and Voronoi diagrams.
AB  - Molecular external structure is important for molecular function, with voids on
      the surface and interior being one of the most important features. Hence,
      recognition of molecular voids and accurate computation of their geometrical
      properties, such as volume, area and topology, are crucial, yet most popular
      algorithms are based on the crude use of sampling points and thus are
      approximations even with a significant amount of computation. In this article, we
      propose an analytic approach to the problem using the Voronoi diagram of atoms
      and the beta-complex. The correctness and efficiency of the proposed algorithm is
      mathematically proved and experimentally verified. The benchmark test clearly
      shows the superiority of BetaVoid to two popular programs: VOIDOO and CASTp. The
      proposed algorithm is implemented in the BetaVoid program which is freely
      available at the Voronoi Diagram Research Center (http://voronoi.hanyang.ac.kr).

PMID- 24677177
TI  - Enthalpic consequences of reduced chloride binding in Andean frog (Telmatobius
      peruvianus) hemoglobin.
AB  - Based on the exothermic nature of heme oxygenation, the O2 affinity of hemoglobin
      (Hb) decreases with increasing temperature, which may be physiologically
      advantageous in augmenting O2 unloading from blood in warm tissues with elevated
      metabolic rates. This negative oxygenation enthalpy (?H (O)) may, however, become
      maladaptive, as in cold-tolerant ungulates where it may hamper O2 unloading in
      cold extremities and commonly is mitigated by an 'additional' chloride-binding
      site that decreases the temperature effect by increasing the endothermic release
      of Cl(-) ions upon O2 binding. Since no previous studies have focused on the
      consequences of reduced Cl(-) binding, I report and compare the enthalpic effects
      of chloride ions and the allosteric effector, ATP, on Hbs of the high-altitude
      aquatic Andean frog Telmatobius peruvianus that lacks the alpha-chain chloride
      binding site, and the lowland (sub-)tropical frog Xenopus laevis that has
      retained this site and exhibits high chloride sensitivity. In contrast to
      Xenopus, Telmatobius Hb exhibits high temperature sensitivity (high negative ?H')
      in the presence of Cl(-) ions, supporting the inverse relationship between the
      number of Cl(-)-binding sites and temperature sensitivity, and extending it to
      ectothermic vertebrates. The radically reduced chloride binding in Telmatobius Hb
      permits assessment of the enthalpy of ATP binding [(?H' ~ -62 kJ (mol ATP)(-1) at
      pH 7.0]-which contrasts sharply with previously reported increases in temperature
      sensitivity by ATP in toad (Bufo bufo) Hb. The high temperature sensitivity
      associated with decreased chloride binding and low phosphate sensitivity of
      Telmatobius Hb likely promotes cutaneous O2 uptake in cold, high-altitude ponds
      and streams.

PMID- 24677178
TI  - Venous drainage of the spine and spinal cord: a comprehensive review of its
      history, embryology, anatomy, physiology, and pathology.
AB  - Venous drainage of the spine and spinal cord is accomplished through a complex
      network of venous structures compartmentalized to intrinsic, extrinsic, and
      extradural systems. As the literature on this topic is scarce, the following
      review was performed to summarize the available literature into a single coherent
      format. The medical literature on the spinal venous system was reviewed using
      online sources as well as historical documents that were not available online in
      regard to history, embryology, anatomy, and physiology with a particular emphasis
      on the pathology affecting this system. The spinal venous system is complex and
      variable. Proper understanding of all aspects is critical for the management of
      the pathology that results from its failure.

PMID- 24677179
TI  - Elevated levels of serum IL-12 and IL-18 are associated with lower frequencies of
      CD4(+)CD25 (high)FOXP3 (+) regulatory t cells in young patients with type 1
      diabetes.
AB  - Type 1 diabetes is thought to involve chronic inflammation, which is manifested
      by the activation and expression of different inflammatory mediators. IL-12 and
      IL-18 are two cytokines that have been shown to exert strong proinflammatory
      activity and have been implicated in the pathogenesis of type 1 diabetes in mice
      and humans. The overproduction of proinflammatory mediators is controlled by
      specialized T cell subset, namely regulatory T cells that express FOXP3
      transcription factor. Since IL-12 and IL-18 mediate inflammatory response and
      Tregs exhibit anti-inflammatory potential, we aimed to examine their reciprocal
      relationship in patients with type 1 diabetes. The study group consisted of 47
      children diagnosed with type 1 diabetes and 28 healthy individuals. Serum levels
      of IL-12 and IL-18 were measured by ELISA, and the peripheral blood
      CD4(+)CD25(high) FOXP3(+) regulatory T cell frequencies were analyzed by flow
      cytometry. Patients with type 1 diabetes had a decreased percentage of
      circulating CD4(+)CD25(high)FOXP3(+) Tregs in comparison to their healthy
      counterparts. In addition, they produced more IL-12 and IL-18 than children from
      the control group. Concentrations of these cytokines positively correlated with
      one another, as well as with CRP and HbA1c. Moreover, the negative association
      between IL-12, IL-18, CRP serum levels, and the frequency of regulatory
      CD4(+)CD25(high)FOXP3(+) Tregs was observed. IL-12 and IL-18 may have direct or
      indirect impact on regulatory T cell subset, which may contribute to their
      reduced frequency in peripheral blood of patients with type 1 diabetes mellitus. 

PMID- 24677180
TI  - Androgen withdrawal fails to induce detectable tissue hypoxia in the rat
      prostate.
AB  - BACKGROUND: It has been reported that significant hypoxia may occur in the rat
      prostate following androgen deprivation (AD). It is well known that hypoxia
      substantially reduces radiation sensitivity of cells both in vitro and in vivo.
      Given that contemporary management of men with intermediate and high-risk
      prostate cancer includes the use of neoadjuvant androgen suppression and
      radiation, AD-induced hypoxia in the prostate could result in suboptimal
      therapeutic results. Given this concern, we fully investigate possible AD-induced
      hypoxia in the ventral prostate (VP) of adult rats by two independent methods.
      METHODS: Tissue pO2 levels in the VP of adult Spraque-Dawley rats were evaluated
      prior to and at various time points following castration by two independent
      techniques. First, an Oxylab tissue oxygen monitor with a 240 MUm probe was used
      for quantitative monitoring of global VP oxygenation. Second, fluorescence
      immunohistochemistry using the hypoxia marker EF5, known to be metabolically
      activated by hypoxic cells, was used to evaluate cell-to-cell variation in
      hypoxia at various days post-castration. RESULTS: Neither the oxygen probe nor
      EF5 method demonstrate any substantive change in pO2 levels in the rat VP at any
      time point post-castration. CONCLUSIONS: We find no evidence that the rat VP
      becomes hypoxic at any point following castration using an animal model that
      closely mimics the human prostate. These data are in contrast to previous reports
      suggesting prostatic hypoxia occurs following AD and provide assurance that our
      present therapeutic strategy of neoadjuvant AD followed by radiation is not
      compromised by AD-induced tissue hypoxia.

PMID- 24677181
TI  - Pd(II)-catalyzed mild C-H ortho arylation and intramolecular amination oriented
      by a phosphinamide group.
AB  - A novel protocol for the Pd-catalyzed ortho-arylation of aryl phosphinamide with
      boronic acid is reported. By using phosphinamide as a new directing group, the
      reaction proceeds efficiently under mild conditions at 408C. Mechanistic studies
      reveal that the reaction proceeds via a PdII to Pd0 cycle. The phosphinamide
      group is also shown to be an effective orienting group for direct C-H amination.

PMID- 24677182
TI  - The trans-10,cis-15 18:2: a missing intermediate of trans-10 shifted rumen
      biohydrogenation pathway?
AB  - The "trans-10 shifted" biohydrogenation pathway is frequently established in the
      rumen when high starch diets are fed to ruminants, resulting in the accumulation
      of trans-10 18:1 in ruminant products. It has been proposed that the "trans-10
      shifted" biohydrogenation pathway of alpha-linolenic acid generates two
      intermediates, the trans-10,cis-15 18:2 and trans-10,cis-12,cis-15 18:3, although
      none of these have been found in the rumen. We analyzed digestive contents and
      meat samples from two trials, where animals were fed: a compound feed diet
      supplemented with 8% oil blend containing linseed oil (samples A); and a forage
      based diet supplemented with 6% linseed oil (samples B). The use of the new SLB
      IL111 chromatographic column allowed the detection of two different 18:2 isomers
      in each sample trial, which could not be resolved when the CP-Sil 88 column is
      used. The two 18:2 isomers were characterized by mass spectrometry using 4,4
      dimethyloxazoline derivatives. However, because they were subject to higher
      temperatures and present different chromatographic properties compared with the
      fatty acid methyl esters, we also used the "covalent adduct chemical ionization"
      technique to confirm the identity of both 18:2 isomers. We detected and
      identified the 10,15-18:2 in samples A and the 11,15-18:2 in samples B. The
      geometry of both isomers was tentatively assigned as trans,cis taking in account
      their elution order and biologic plausibility. As far as we know, this is the
      first time that the trans-10,cis-15 18:2 has been found in ruminant digestive
      contents and meat samples associated with the "trans-10 shifted" biohydrogenation
      pathway of alpha-linolenic acid.

PMID- 24677183
TI  - Ephrin B2/EphB4 mediates the actions of IGF-I signaling in regulating
      endochondral bone formation.
AB  - Ephrin B2/EphB4 mediates interactions among osteoblasts (OBs), osteoclasts
      (OCLs), and chondrocytes to regulate their differentiation. We investigated the
      role of ephrin B2/EphB4 signaling in mediating the anabolic effects of insulin
      like growth factor-I (IGF-I) and parathyroid hormone (PTH) on those cells and
      overall endochondral bone formation. Immunohistochemistry demonstrated that the
      expression of ephrin B2 in OBs, OCLs, and osteocytes, and the expression of EphB4
      in OBs and osteocytes was dramatically decreased in global IGF-I knockout mice.
      Inactivation of EphB4 by EphB4 small, interfering RNA (siRNA) in cultured bone
      marrow stromal cells significantly decreased the mRNA levels of OB
      differentiation markers and abolished the stimulatory effects of IGF-I on these
      markers. Blocking the interaction of EphB4 and ephrin B2 in the OB-OCL cocultures
      with the EphB4 specific peptide TNYL-RAW or deletion of ephrin B2 in OCL prior to
      coculture led to fewer and smaller tartrate-resistant acid phosphatase (TRAP)
      positive cells, decreased expression of OB differentiation markers, and blunted
      response to IGF-I for both OCL and OB differentiation. In the growth plate, both
      ephrin B2 and EphB4 are expressed in late stage proliferating and prehypertrophic
      chondrocytes, and their expression was decreased in mice lacking the IGF-I
      receptor specifically in chondrocytes. In vitro, blocking the interaction of
      EphB4 and ephrin B2 in chondrogenic ATDC5 cells with TNYL-RAW significantly
      decreased both basal and IGF1-induced expression of type II and type X collagen.
      In the cocultures of ATDC5 cells and spleen cells (osteoclast precursors), TNYL
      RAW decreased the numbers of TRAP-positive cells and the expression of nuclear
      factor of activated T cells, cytoplasmic 1 (NFATc1) and receptor activator of NF
      kappaB (RANK), and blocked their stimulation by IGF-I. Our data indicate that IGF
      I/IGF-IR signaling promotes OB, OCL, and chondrocyte differentiation via ephrin
      B2/EphB4 mediated cell-cell communication.

PMID- 24677185
TI  - Arthroplasty in young adults: options, techniques, trends, and results.
AB  - Total knee arthroplasty (TKA) has been established as a very successful and
      commonly performed procedure for primary and secondary osteoarthritis, and also
      for inflammatory arthropathies of the knee in all age groups and both genders. It
      has predominantly been used as a procedure in the age group of patients 65 years
      and above. Consequently, the literature is replete with data relevant to various
      issues associated with TKA in the above 65 years age group population. Although
      there is reasonable clarity and consensus on the broad parameters of the use of
      TKA in the above 65 years age group (older), this cannot be said for the same
      issue as relevant to the below 65 years age group (young adults). Over the last 2
      decades there has been an increasing tendency toward the use of TKA in young
      adults, with some countries reporting a 5-fold increase in the last 10 years [1].
      The present article is designed to review the most recent literature specific to
      this subject and assess it vis-a-vis various issues as listed in the subsequent
      text, with the aim of highlighting evolving thoughts and trends, which could be
      useful for decision making by clinicians practicing in the community. 

PMID- 24677186
TI  - Muscle-fat magnetic resonance imaging: applications.

PMID- 24677184
TI  - Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1
      hepatitis C virus in interferon-ineligible/intolerant individuals.
AB  - Treatment guidance for chronic hepatitis C (CHC) released by the American
      Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases
      Society of America (IDSA) offers two options for interferon (IFN)
      ineligible/intolerant individuals with genotype 1 infection: sofosbuvir/ribavirin
      (SOF/RBV) for 24 weeks or sofosbuvir/simeprevir (SOF/SMV) for 12 weeks. A 24-week
      course of SOF/RBV costs approximately US$169,000, with sustained virologic
      response (SVR) rates ranging from 52% to 84%; 12 weeks of SOF/SMV costs
      approximately $150,000, with SVR between 89% and 100%. Because SOF/SMV is
      currently used off-label, debate exists among physicians and payers about whether
      it should be prescribed and covered. This article presents a cost-effectiveness
      analysis of these two treatment regimens accounting for costs of drugs, treatment
      related medical care, retreatment for individuals who do not achieve SVR, and
      natural history of continued HCV infection after failed retreatment. Analysis
      uses a Markov model with a lifetime horizon and a societal perspective. In the
      base-case scenario, SOF/SMV dominated SOF/RBV in a modeled 50-year-old cohort of
      treatment-naive and -experienced subjects, excluding those who failed earlier
      therapy with telaprevir or boceprevir. SOF/SMV yielded lower costs and more
      quality-adjusted life years (QALYs) for the average subject, compared to SOF/RBV
      ($165,336 and 14.69 QALYs vs. $243,586 and 14.45 QALYs, respectively). In base
      case cost analysis, the SOF/SMV treatment strategy saved $91,590 per SVR,
      compared to SOF/RBV. Under all one-way sensitivity scenarios, SOF/SMV remained
      dominant and resulted in cost savings. CONCLUSIONS: These results suggest that a
      12-week course of SOF/SMV is a more cost-effective treatment for genotype 1 CHC
      than 24 weeks of SOF/RBV among IFN-ineligible/intolerant individuals, supporting
      the AASLD/IDSA guidance and offering implications for both clinical and
      regulatory decision making as well as pharmaceutical pricing.

PMID- 24677187
TI  - Design of amphiphilic peptide geometry towards biomimetic self-assembly of chiral
      mesoporous silica.
AB  - In nature, diatoms and sponges are exquisite examples of well-defined structures
      produced by silica biomineralisation, in which proteins play an important role.
      However, the artificial peptide templating route for the silica mesostructure
      remains a formidable and unsolved challenge. Herein, we report our effort on the
      design of amphiphilic peptides for synthesising a highly ordered two-dimensional
      (2D)-hexagonal and lamellar chiral silica mesostructure using
      trimethoxysilylpropyl-N,N,N-trimethylammonium chloride as the co-structure
      directing agent (CSDA). The geometry of the peptide was designed by adding
      proline residues into the hydrophobic chain of the peptide to break the b-sheet
      conformation by weakening the intermolecular hydrogen bonds; this led to the
      mesophase transformation from the most general lamellar structure to the 2D
      hexagonal P6mm mesostructure by increasing the amphiphilic molecules packing
      parameter g. Enantiomerically pure chiral mesostructures were formed thanks to
      the intrinsic chirality and relatively strong intermolecular hydrogen bonds of
      peptides.

PMID- 24677188
TI  - Thin films with ultra-low thermal expansion.
AB  - Ultra-low coefficient of thermal expansion (CTE) is an elusive property, and
      narrow temperature ranges of operation and poor mechanical properties limit the
      use of conventional materials with low CTE. We structured a periodic micro-array
      of bi-metallic cells to demonstrate ultra-low effective CTE with a wide
      temperature range. These engineered tunable CTE thin film can be applied to
      minimize thermal fatigue and failure of optics, semiconductors, biomedical
      sensors, and solar energy applications. 

PMID- 24677190
TI  - Type I and type III interferon-induced immune response: it's a matter of kinetics
      and magnitude.

PMID- 24677191
TI  - PKCs: pernicious kinase culprits in acetaminophen pathogenesis.

PMID- 24677193
TI  - Pathological functions of interleukin-22 in chronic liver inflammation and
      fibrosis with hepatitis B virus infection by promoting T helper 17 cell
      recruitment.
AB  - It is well established that interleukin (IL)-22 has hepatoprotective and
      antifibrotic functions in acute liver injury models; however, its function in
      patients with liver fibrosis and liver cirrhosis (LC) remains obscure. In the
      current study, we demonstrated that expression of numerous IL-22 pathway
      associated genes was significantly up-regulated in hepatitis B virus (HBV)
      infected liver tissues, compared to normal controls, through microarray analysis.
      In agreement with these findings, liver-infiltrating IL-22(+) cells were largely
      increased in HBV-infected patients with LC, compared to those without LC or
      healthy subjects, and were positively associated with liver fibrosis staging
      scores. Immunohistochemistry and flow cytometric analyses revealed that IL-22 was
      produced by multiple intrahepatic immune cells and, preferentially, by T-helper
      (Th) 17 cells in LC patients. In an HBV transgenic (Tg) mouse model of T-cell
      mediated chronic liver inflammation and fibrosis, blockade of IL-22 attenuated
      hepatic expression of chemokine (C-X-C motif) ligand 10 and chemokine (C-C motif)
      ligand 20 (CCL20) and subsequently reduced Th17 recruitment and liver
      inflammation and fibrosis progression. In vitro treatment with IL-22 stimulated
      hepatic stellate cells (HSCs) to secrete several chemokines and subsequently
      promoted Th17 cell chemotaxis. Blocking C-X-C chemokine receptor type 3 or CCL20
      reduced Th17 cell chemotaxis by IL-22-treated HSCs. CONCLUSIONS: IL-22 plays a
      pathological role in exacerbating chronic liver inflammation and fibrosis by
      recruiting hepatic Th17 cells in HBV-infected patients and HBV Tg mice.

PMID- 24677192
TI  - Hepatitis C disease severity in living versus deceased donor liver transplant
      recipients: an extended observation study.
AB  - Donor factors influence hepatitis C virus (HCV) disease severity in liver
      transplant (LT) recipients. Living donors, because they are typically young and
      have short cold ischemic times, may be advantageous for HCV-infected patients.
      Among HCV-infected patients in the Adult-to-Adult Living Donor Liver
      Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median
      4.7 years, advanced fibrosis (Ishak stage >=3) and graft loss were determined.
      The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor
      LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively.
      Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for
      doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were
      associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence
      interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft
      survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P =
      0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P =
      0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74
      for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of
      AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95%
      CI: 0.49-1.18, P = 0.23). CONCLUSION: Donor type does not affect the probability
      of advanced fibrosis or patient and graft survival in HCV-infected recipients.
      Thus, while LDLT offers the advantage of shorter wait times, there is no apparent
      benefit for HCV disease progression. Biliary strictures have a negative effect on
      HCV fibrosis severity and graft survival, and a high AST at LT may be an
      important predictor of fibrosis risk post-LT.

PMID- 24677194
TI  - Liver-primed CD8+ T cells suppress antiviral adaptive immunity through galectin-9
      independent T-cell immunoglobulin and mucin 3 engagement of high-mobility group
      box 1 in mice.
AB  - The liver is a tolerogenic environment exploited by persistent infections, such
      as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous
      hepatotropic adenovirus infection, liver-primed antiviral CD8(+) T cells fail to
      produce proinflammatory cytokines and do not display cytolytic activity
      characteristic of effector CD8(+) T cells generated by infection at an
      extrahepatic, that is, subcutaneous, site. Importantly, liver-generated CD8(+) T
      cells also appear to have a T-regulatory (Treg) cell function exemplified by
      their ability to limit proliferation of antigen-specific T-effector (Teff ) cells
      in vitro and in vivo via T-cell immunoglobulin and mucin 3 (Tim-3) expressed by
      the CD8(+) Treg cells. Regulatory activity did not require recognition of the
      canonical Tim-3 ligand, galectin-9, but was dependent on CD8(+) Treg cell-surface
      Tim-3 binding to the alarmin, high-mobility group box 1 (HMGB-1). CONCLUSION:
      Virus-specific Tim-3(+) CD8(+) T cells operating through HMGB-1 recognition in
      the setting of acute and chronic viral infections of the liver may act to dampen
      hepatic T-cell responses in the liver microenvironment and, as a consequence,
      limit immune-mediated tissue injury or promote the establishment of persistent
      infections.

PMID- 24677195
TI  - Hepatocellular carcinoma screening in patients with compensated hepatitis C virus
      (HCV)-related cirrhosis aware of their HCV status improves survival: a modeling
      approach.
AB  - Because of the ongoing debate on the benefit of ultrasound (US) screening for
      hepatocellular carcinoma (HCC), we assessed the impact of screening on hepatitis
      C virus (HCV)-related compensated cirrhosis patients aware of their HCV status. A
      Markov model simulated progression from HCC diagnosis to death in 700 patients
      with HCV-related compensated cirrhosis aware of their HCV status to estimate life
      expectancy (LE) and cumulative death at 5 years. Five scenarios were compared:
      S1, no screening; S2, screening by currently existing practices (57% access and
      effectiveness leading to the diagnosis of 42% at Barcelona Clinic Liver Cancer
      stage [BCLC-0/A]); S3, S2 with increased access (97%); S4, S2 with an efficacy of
      screening close to that achieved in a randomized controlled trial leading to the
      diagnosis of 87% of patients at stage BCLC-0/A; S5, S3+S4. The analysis was
      corrected for lead-time bias. Currently existing practices of HCC screening
      increased LE by 11 months and reduced HCC mortality at 5 years by 6% compared to
      no screening (P = 0.0013). Compared to current screening practices, we found
      that: 1) increasing the rate of access to screening would increase LE by 7 months
      and reduce HCC mortality at 5 years by 5% (P = 0.045); 2) optimal screening would
      increase LE by 14 months and reduce HCC mortality at 5 years by 9% (P = 0.0002);
      3) the combination of an increased rate of access and optimal effectiveness of
      HCC screening would increase LE by 31 months and decrease HCC mortality at 5
      years by 20% (P < 0.0001). CONCLUSION: The present study shows that US screening
      for HCC in patients with compensated HCV-related cirrhosis aware of their HCV
      status improves survival and emphasizes the crucial role of screening
      effectiveness.

PMID- 24677196
TI  - Protection against RNA-induced liver damage by myeloid cells requires type I
      interferon and IL-1 receptor antagonist in mice.
AB  - Cell types and mechanisms involved in type I interferon (IFN)-mediated anti
      inflammatory effects are poorly understood. Upon injection of artificial double
      stranded RNA (poly(I:C)), we observed severe liver damage in type I IFN-receptor
      (IFNAR) chain 1-deficient mice, but not in wild-type (WT) controls. Studying mice
      with conditional IFNAR ablations revealed that IFNAR triggering of myeloid cells
      is essential to protect mice from poly(I:C)-induced liver damage. Accordingly, in
      poly(I:C)-treated WT, but not IFNAR-deficient mice, monocytic myeloid-derived
      suppressor cells (MDSCs) were recruited to the liver. Comparing WT and IFNAR
      deficient mice with animals deficient for the IFNAR on myeloid cells only
      revealed a direct IFNAR-dependent production of the anti-inflammatory cytokine
      interleukin-1 receptor antagonist (IL-1RA) that could be assigned to liver
      infiltrating cells. Upon poly(I:C) treatment, IFNAR-deficient mice displayed both
      a severe lack of IL-1RA production and an increased production of proinflammatory
      IL-1beta, indicating a severely imbalanced cytokine milieu in the liver in
      absence of a functional type I IFN system. Depletion of IL-1beta or treatment
      with recombinant IL-1RA both rescued IFNAR-deficient mice from poly(I:C)-induced
      liver damage, directly linking the deregulated IL-1beta and IL-1RA production to
      liver pathology. CONCLUSION: Type I IFN signaling protects from severe liver
      damage by recruitment of monocytic MDSCs and maintaining a balance between IL
      1beta and IL-1RA production.

PMID- 24677189
TI  - The effects of novel and newly approved antipsychotics on serum prolactin levels:
      a comprehensive review.
AB  - Since the 1970s, clinicians have increasingly become more familiar with
      hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication,
      which remains the cornerstone of pharmacological treatment for patients with
      schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as
      a group is, compared with use of the first-generation antipsychotics, associated
      with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL
      levels for each of these compounds in reports often remain incomplete or
      inaccurate. Moreover, at this moment, no review has been published about the
      effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone
      on PRL levels. The objective of this review is to describe PRL physiology; PRL
      measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence
      figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in
      adolescent and adult patients; and revisit lingering questions regarding this
      hormone. A literature search, using the MEDLINE database (1966-December 2013),
      was conducted to identify relevant publications to report on the state of the art
      of HPRL and to summarize the available evidence with respect to the propensity of
      the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review
      shows that although HPRL usually is defined as a sustained level of PRL above the
      laboratory upper limit of normal, limit values show some degree of variability in
      clinical reports, making the interpretation and comparison of data across studies
      difficult. Moreover, many reports do not provide much or any data detailing the
      measurement of PRL. Although the highest rates of HPRL are consistently reported
      in association with amisulpride, risperidone and paliperidone, while aripiprazole
      and quetiapine have the most favorable profile with respect to this outcome, all
      SGAs can induce PRL elevations, especially at the beginning of treatment, and
      have the potential to cause new-onset HPRL. Considering the PRL-elevating
      propensity of the newly approved antipsychotics, evidence seems to indicate these
      agents have a PRL profile comparable to that of clozapine (asenapine and
      iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with
      antipsychotic medication generally are dose dependant. However, antipsychotics
      having a high potential for PRL elevation (amisulpride, risperidone and
      paliperidone) can have a profound impact on PRL levels even at relatively low
      doses, while PRL levels with antipsychotics having a minimal effect on PRL, in
      most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all
      dosages. Although tolerance and decreases in PRL values after long-term
      administration of PRL-elevating antipsychotics can occur, the elevations, in most
      cases, remain above the upper limit of normal. PRL profiles of antipsychotics in
      children and adolescents seem to be the same as in adults. The hyperprolactinemic
      effects of antipsychotic medication are mostly correlated with their affinity for
      dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and
      probably other neurotransmitter mechanisms) and their blood-brain barrier
      penetrating capability. Even though antipsychotics are the most common cause of
      pharmacologically induced HPRL, recent research has shown that HPRL can be pre
      existing in a substantial portion of antipsychotic-naive patients with first
      episode psychosis or at-risk mental state. 

PMID- 24677198
TI  - The authors' reply.

PMID- 24677199
TI  - Efficient atropodiastereoselective access to 5,5'-bis-1,2,3-triazoles: studies on
      1-glucosylated 5-halogeno 1,2,3-triazoles and their 5-substituted derivatives as
      glycogen phosphorylase inhibitors.
AB  - Whereas copper-catalyzed azide-alkyne cycloaddition (CuAAC) between acetylated
      beta-D-glucosyl azide and alkyl or phenyl acetylenes led to the corresponding 4
      substituted 1-glucosyl-1,2,3-triazoles in good yields, use of similar conditions
      but with 2 equiv CuI or CuBr led to the 5-halogeno analogues (>71 %). In
      contrast, with 2 equiv CuCl and either propargyl acetate or phenyl acetylene, the
      major products (>56 %) displayed two 5,5'-linked triazole rings resulting from
      homocoupling of the 1-glucosyl-4-substituted 1,2,3-triazoles. The 4-phenyl
      substituted compounds (acetylated, O-unprotected) and the acetylated 4
      acetoxymethyl derivative existed in solution as a single form (d.r.>95:5), as
      shown by NMR spectroscopic analysis. The two 4-phenyl substituted structures were
      unambiguously identified for the first time by X-ray diffraction analysis, as
      atropisomers with aR stereochemistry. This represents one of the first efficient
      and highly atropodiastereoselective approaches to glucose-based bis-triazoles as
      single atropisomers. The products were purified by standard silica gel
      chromatography. Through Sonogashira or Suzuki cross-couplings, the 1-glucosyl-5
      halogeno-1,2,3-triazoles were efficiently converted into a library of 1,2,3
      triazoles of the 1-glucosyl-5-substituted (alkynyl, aryl) type. Attempts to
      achieve Heck coupling to methyl acrylate failed, but a stable palladium
      associated triazole was isolated and analyzed by (1)H NMR and MS. O-Unprotected
      derivatives were tested as inhibitors of glycogen phosphorylase. The modest
      inhibition activities measured showed that 4,5-disubstituted 1-glucosyl-1,2,3
      triazoles bind weakly to the enzyme. This suggests that such ligands do not fit
      the catalytic site or any other binding site of the enzyme.

PMID- 24677197
TI  - Epidermal growth factor receptor inhibition attenuates liver fibrosis and
      development of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer
      related mortality in the United States. Because of the lack of viable treatment
      options for HCC, prevention in high-risk patients has been proposed as an
      alternative strategy. The main risk factor for HCC is cirrhosis and several lines
      of evidence implicate epidermal growth factor (EGF) in the progression of
      cirrhosis and development of HCC. We therefore examined the effects of the EGF
      receptor (EGFR) inhibitor erlotinib on liver fibrogenesis and hepatocellular
      transformation in three different animal models of progressive cirrhosis: a rat
      model induced by repeated, low-dose injections of diethylnitrosamine (DEN), a
      mouse model induced by carbon tetrachloride (CCl4 ), and a rat model induced by
      bile duct ligation (BDL). Erlotinib reduced EGFR phosphorylation in hepatic
      stellate cells (HSC) and reduced the total number of activated HSC. Erlotinib
      also decreased hepatocyte proliferation and liver injury. Consistent with all
      these findings, pharmacological inhibition of EGFR signaling effectively
      prevented the progression of cirrhosis and regressed fibrosis in some animals.
      Moreover, by alleviating the underlying liver disease, erlotinib blocked the
      development of HCC and its therapeutic efficacy could be monitored with a
      previously reported gene expression signature predictive of HCC risk in human
      cirrhosis patients. CONCLUSION: These data suggest that EGFR inhibition using
      Food and Drug Administration-approved inhibitors provides a promising therapeutic
      approach for reduction of fibrogenesis and prevention of HCC in high-risk
      cirrhosis patients who can be identified and monitored by gene expression
      signatures.

PMID- 24677201
TI  - Arterial stiffness in carpal tunnel syndrome: role of antihypertensive drugs.

PMID- 24677200
TI  - Tentative characterisation of iridoids, phenylethanoid glycosides and flavonoid
      derivatives from Globularia alypum L. (Globulariaceae) leaves by LC-ESI-QTOF-MS.
AB  - INTRODUCTION: Globularia alypum L., belonging to the Globulariaceae family, is a
      perennial wild shrub found throughout the Mediterranean area, Europe, and Africa.
      This plant is widely used to treat many diseases, but no previous work on the
      phytochemical composition of the Algerian G. alypum species has yet been
      reported. OBJECTIVE: To investigate the phytoconstituents of the methanolic
      extract of G. alypum using an LC-ESI-QTOF-MS method. METHODS: Ground air-dried
      leaves of G. alypum were macerated with methanol at room temperature for 24 h.
      The supernatant was filtered and concentrated to dryness under reduced pressure
      in a rotary evaporator, and extracts were recovered with methanol and filtered.
      Afterwards, the G. alypum extract was injected into the LC-ESI-QTOF-MS system.
      RESULTS: The combined LC-MS/MS led to the tentative characterisation of 63
      phytochemicals. In this work, a large number of compounds have been characterised
      in the leaf-extract analysis of this plant. Among others, 24 iridoids and
      secoiridoids were found, of which nine compounds have not previously been
      recorded in G. alypum. Also, nine unusual phenylethanoid glycosides were
      characterised for the first time in this species. CONCLUSION: The method used has
      proved to be a valued tool for the characterisation of a wide range of compounds
      from G. alypum leaves. This work constitutes a detailed investigation of the
      chemical composition of G. alypum leaves, which are widely used in different
      traditional systems of medicine.

PMID- 24677202
TI  - Variable-color light-emitting diodes using GaN microdonut arrays.
AB  - Microdonut-shaped GaN/Inx Ga1-x N light-emitting diode (LED) microarrays are
      fabricated for variable-color emitters. The figure shows clearly donut-shaped
      light emission from all the individual microdonut LEDs. Furthermore, microdonut
      LEDs exhibit spatially-resolved blue and green EL colors, which can be tuned by
      either controlling the external bias voltage or changing the size of the
      microdonut LED. 

PMID- 24677203
TI  - Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral
      or systemic embolism in people with non-valvular atrial fibrillation.
AB  - BACKGROUND: Chronic anticoagulation with vitamin K antagonists (VKAs) prevents
      ischaemic stroke and systemic embolism in people with non-valvular atrial
      fibrillation (AF) but dose adjustment, coagulation monitoring and bleeding limits
      its use. Direct thrombin inhibitors (DTIs) are under investigation as potential
      alternatives. OBJECTIVES: To assess (1) the comparative efficacy of long-term
      anticoagulation using DTIs versus VKAs on vascular deaths and ischaemic events in
      people with non-valvular AF, and (2) the comparative safety of chronic
      anticoagulation using DTIs versus VKAs on (a) fatal and non-fatal major bleeding
      events including haemorrhagic strokes, (b) adverse events other than bleeding and
      ischaemic events that lead to treatment discontinuation and (c) all-cause
      mortality in people with non-valvular AF. SEARCH METHODS: We searched the
      Cochrane Stroke Group Trials Register (July 2013), the Cochrane Central Register
      of Controlled Trials (CENTRAL), (The Cochrane Library, May 2013), MEDLINE (1950
      to July 2013), EMBASE (1980 to October 2013), LILACS (1982 to October 2013) and
      trials registers (September 2013). We also searched the websites of clinical
      trials and pharmaceutical companies and handsearched the reference lists of
      articles and conference proceedings. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing DTIs versus VKAs for prevention of stroke and systemic
      embolism in people with non-valvular AF. DATA COLLECTION AND ANALYSIS: All three
      review authors independently performed data extraction and assessment of risk of
      bias. Primary analyses compared all DTIs combined versus warfarin. We performed
      post hoc analyses excluding ximelagatran because this drug was withdrawn from the
      market owing to safety concerns. MAIN RESULTS: We included eight studies
      involving a total of 27,557 participants with non-valvular AF and one or more
      risk factors for stroke; 26,601 of them were assigned to standard doses groups
      and included in the primary analysis. The DTIs: dabigatran 110 mg twice daily and
      150 mg twice daily (three studies, 12,355 participants), AZD0837 300 mg once per
      day (two studies, 233 participants) and ximelagatran 36 mg twice per day (three
      studies, 3726 participants) were compared with the VKA warfarin (10,287
      participants). Overall risk of bias and statistical heterogeneity of the studies
      included were low.The odds of vascular death and ischaemic events were not
      significantly different between all DTIs and warfarin (odds ratio (OR) 0.94, 95%
      confidence interval (CI) 0.85 to 1.05). Sensitivity analysis by dose of
      dabigatran on reduction in ischaemic events and vascular mortality indicated that
      dabigatran 150 mg twice daily was superior to warfarin although the effect
      estimate was of borderline statistical significance (OR 0.86, 95% CI 0.75 to
      0.99). Sensitivity analyses by other factors did not alter the results. Fatal and
      non-fatal major bleeding events, including haemorrhagic strokes, were less
      frequent with the DTIs (OR 0.87, 95% CI 0.78 to 0.97). Adverse events that led to
      discontinuation of treatment were significantly more frequent with the DTIs (OR
      2.18, 95% CI 1.82 to 2.61). All-cause mortality was similar between DTIs and
      warfarin (OR 0.91, 95% CI 0.83 to 1.01). AUTHORS' CONCLUSIONS: DTIs were as
      efficacious as VKAs for the composite outcome of vascular death and ischaemic
      events and only the dose of dabigatran 150 mg twice daily was found to be
      superior to warfarin. DTIs were associated with fewer major haemorrhagic events,
      including haemorrhagic strokes. Adverse events that led to discontinuation of
      treatment occurred more frequently with the DTIs. We detected no difference in
      death from all causes.

PMID- 24677205
TI  - The effects of the therapist's disengaged feelings on the in-session process in
      psychodynamic psychotherapy.
AB  - The primary aim of this article was to explore the effects of the therapist's
      disengaged feelings (i.e., bored, tired of, sleepy, indifferent, aloof) in
      psychodynamic therapy. The Transference Work Scale was used in combination with
      the Defense Mechanism Rating Scales and Structural Analyses of Social Behavior to
      explore the in-session process in 2 therapies with female patients with
      interpersonal problems. Analyses showed differences in in-session processes
      (i.e., defense mechanisms; transference work; degree of affiliation and
      interdependence in the dialogue) and treatment outcome between therapies
      characterized by a low versus a higher degree of disengaged feelings. Compared to
      the case with the engaged therapist, the disengaged therapist showed poorer
      interaction and less response to transference and defense interpretation. When
      aware of their disengaged feelings, therapists are advised to encourage their
      patients to discuss the patient-therapist interaction.

PMID- 24677204
TI  - The high-throughput synthesis and phase characterisation of amphiphiles: a sweet
      case study.
AB  - A new method for the discovery of amphiphiles by using high-throughput (HT)
      methods to synthesise and characterise a library of galactose- and glucose
      containing amphiphilic compounds is presented. The copper-catalysed azide-alkyne
      cycloaddition (CuAAC) "click" reaction between azide-tethered simple sugars and
      alkyne-substituted hydrophobic tails was employed to synthesise a library of
      compounds with systematic variations in chain length and unsaturation in a 24
      vial array format. The liquid-crystalline phase behaviour was characterised in a
      HT manner by using synchrotron small-angle X-ray scattering (SSAXS). The observed
      structural variation with respect to chain parameters, including chain length and
      degree of unsaturation, is discussed, as well as hydration effects and degree of
      hydrogen bonding between head groups. The validity of our HT screening approach
      was verified by resynthesising a short-chain glucose amphiphile. A separate phase
      analysis of this compound confirmed the presence of numerous lyotropic liquid
      crystalline phases.

PMID- 24677206
TI  - Screening for cognitive and affective dysfunction in patients suspected of mild
      cognitive impairment.
AB  - OBJECTIVE: Disturbances of affect expression and perception, as well as accuracy
      of predicting memory difficulties, have been reported in various brain
      dysfunctional groups. Screening tests of higher cerebral functions seldom sample
      these dimensions. The goal of this study was to determine if patients with mild
      cognitive impairment (MCI) of the amnestic type would demonstrate impairments in
      these domains, as well as show expected memory deficits. METHODS: Thirty-nine
      French-speaking patients with a clinical diagnosis of MCI were compared with 39
      age- and education-matched normal functioning individuals on the French
      translation of the Barrow Neurological Institute Screen for Higher Cerebral
      Functions (BNIS). Patients and controls also made subjective ratings regarding
      their cognitive and affective functioning in everyday life. RESULTS: Patients
      with MCI performed significantly worse than controls on the BNIS subtests
      sampling memory, orientation, affect expression and perception, and accurate
      prediction of memory performance. They did not differ on other subtests of the
      BNIS, as predicted. Poor self-awareness (i.e., inaccurate prediction of the
      number of words one could recall after distraction) correlated with self-reported
      deficits in several areas of cognitive and affective functioning. CONCLUSION:
      This sample of MCI patients demonstrated disturbances not only in memory but also
      in self-awareness and affect expression and perception on the BNIS. These
      dimensions should be included in the neuropsychological assessment of patients
      suspected of MCI.

PMID- 24677207
TI  - JAK2V617F mutation status and allele burden in classical Ph-negative
      myeloproliferative neoplasms in Japan.
AB  - JAK2V617F, a gain-of-function mutation in the tyrosine kinase JAK2, is frequently
      detected in classical myeloproliferative neoplasms (MPNs). In the present study,
      we determined the JAK2V617F allele burden in Japanese MPN patients using
      alternately binding probe competitive-polymerase chain reaction, a highly
      quantitative method recently developed by our group. Although we observed strong
      similarities in terms of epidemiological parameters associated with the JAK2V617F
      allele burden between our cohort and others, we found a higher JAK2V617F allele
      burden in Japanese polycythemia vera (PV) patients and lower frequencies of
      thrombosis in Japanese MPN patients compared with previous reports. In addition,
      despite the presence of high red blood cell counts, some patients bearing the
      JAK2V617F mutation were not diagnosed as PV, as their hemoglobin values were
      lower than the WHO PV criterion. In these patients, the JAK2V617F allele burden
      was strikingly similar to that in PV patients fulfilling the 2008 WHO criteria,
      suggesting that these patients can be classified as PV. Although isotopic
      measurement of red cell mass (RCM) is required for definitive diagnosis of PV,
      our data suggest that precise measurement of the JAK2V617F allele burden may
      improve the diagnosis of PV when RCM has not been determined. 

PMID- 24677208
TI  - Bortezomib plus melphalan and prednisone (VMP regimen) as the initial treatment
      for IgE multiple myeloma: a case study.
AB  - Patients with IgE multiple myeloma have poor prognosis. Due to the rarity of this
      condition, no standard treatment has been developed. As the VMP regimen
      (bortezomib plus melphalan and prednisone) has been reported to be highly
      effective in the treatment of other types of myeloma, we treated a patient with
      newly diagnosed IgE myeloma using the VMP regimen. Her myeloma responded well to
      VMP regimen. The results of this case report thus suggest that physicians may
      consider VMP regimen for use as the initial treatment for IgE myeloma. 

PMID- 24677209
TI  - Keeping reproductive science visible, viable, and valuable-a call to rethink how
      we publish.

PMID- 24677210
TI  - Lack of association of INS VNTR polymorphism with polycystic ovary syndrome: a
      meta-analysis.
AB  - PURPOSE: An association between the INS VNTR polymorphisms and polycystic ovary
      syndrome (PCOS) susceptibility has been reported in previous studies, but the
      results were inconsistent. This study was conducted to explore this association
      using meta-analysis. METHODS: PubMed, Embase, and China National Knowledge
      Infrastructure (CNKI) were searched according to predefined criteria for all
      relevant studies published up to August 2013. Four genetic models, together with
      odds ratios (ORs) and 95 % confidence intervals (CI), were calculated. Subgroup
      analyses were performed by ethnicity, anovulatory PCOS, and Hardy-Weinberg
      equilibrium (HWE) in the controls. RESULTS: In total, 13 case-control studies,
      including 1,767 cases and 4,108 controls, were included. No significant
      association was detected in overall population in all models (III/III vs. I/I: OR
      = 1.200, 95%CI = 0.866-1.664, P=0.277; I/III vs. I/I: OR = 1.041, 95%CI = 0.880
      1.232, P=0.637; III/III + I/III vs. I/I: OR = 1.191, 95%CI = 0.912-1.554,
      P=0.199; III/III vs. I/III + I/I: OR = 1.100, 95%CI = 0.816-1.484, P=0.531), the
      same as in Caucasian and Asian populations. When the studies were limited to
      conform to HWE, the results remained persistent and robust. The anovulation
      subgroup showed significantly elevated risk in the I/III vs. I/I (OR = 1.460,
      95%CI = 1.017-2.095, P=0.040). CONCLUSIONS: This meta-analysis revealed no
      significant association between INS VNTR polymorphisms and the risk of PCOS in
      the overall population, while it supported that variance may be associated with
      susceptibility to PCOS with anovulation. Further confirmation is needed from more
      well-designed and larger studies.

PMID- 24677211
TI  - Targeting the LRP5 pathway improves bone properties in a mouse model of
      osteogenesis imperfecta.
AB  - The cell surface receptor low-density lipoprotein receptor-related protein 5
      (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense
      mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by
      reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST).
      Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a
      human HBM-causing mutation have increased bone mass and strength. Osteogenesis
      imperfecta (OI) is a skeletal fragility disorder predominantly caused by
      mutations that affect type I collagen. We tested whether the LRP5 pathway can be
      used to improve bone properties in animal models of OI. First, we mated
      Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We
      found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly
      increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+)
      littermates. The improved bone properties were not a result of altered mRNA
      expression of type I collagen or its chaperones, nor were they due to changes in
      mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with
      a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that
      antibody-treated mice had significantly increased bone mass and strength compared
      to vehicle-treated littermates. These findings indicate increasing bone
      formation, even without altering bone collagen composition, may benefit patients
      with OI.

PMID- 24677213
TI  - A chronic disease management model for chronic liver failure.

PMID- 24677214
TI  - Spectroscopic monitoring of the acidity of water films on Ru(0001): orientation
      specific acidity of adsorbed water.
AB  - We examined the acid-base properties of water films adsorbed onto a Ru(0001)
      substrate by using surface spectroscopic methods in vacuum environments. Ammonia
      adsorption experiments combined with low-energy sputtering (LES), reactive ion
      scattering (RIS), reflection-absorption infrared spectroscopy (RAIRS) and
      temperature-programmed desorption (TPD) measurements showed that the adsorbed
      water is acidic enough to transfer protons to ammonia. Only the water molecules
      in an intact water monolayer and water clusters larger than the hexamer exhibit
      such acidity, whereas small clusters, a thick ice film or a partially dissociated
      water monolayer that contains OH, H2O and H species are not acidic. The
      observations indicate the orientation-specific acidity of adsorbed water. The
      acidity stems from water molecules with H-down adsorption geometry present in the
      monolayer. However, the dissociation of water into H and OH on the surface does
      not promote but rather suppresses the proton transfer to ammonia.

PMID- 24677215
TI  - Author's reply to Paillard T: "sport-specific balance develops specific postural
      skills".

PMID- 24677212
TI  - WeFold: a coopetition for protein structure prediction.
AB  - The protein structure prediction problem continues to elude scientists. Despite
      the introduction of many methods, only modest gains were made over the last
      decade for certain classes of prediction targets. To address this challenge, a
      social-media based worldwide collaborative effort, named WeFold, was undertaken
      by 13 labs. During the collaboration, the laboratories were simultaneously
      competing with each other. Here, we present the first attempt at "coopetition" in
      scientific research applied to the protein structure prediction and refinement
      problems. The coopetition was possible by allowing the participating labs to
      contribute different components of their protein structure prediction pipelines
      and create new hybrid pipelines that they tested during CASP10. This manuscript
      describes both successes and areas needing improvement as identified throughout
      the first WeFold experiment and discusses the efforts that are underway to
      advance this initiative. A footprint of all contributions and structures are
      publicly accessible at http://www.wefold.org.

PMID- 24677216
TI  - Outcomes After Total Ankle Replacement in Association With Ipsilateral Hindfoot
      Arthrodesis.
AB  - BACKGROUND: Ipsilateral hindfoot arthrodesis in combination with total ankle
      replacement (TAR) may diminish functional outcome and prosthesis survivorship
      compared to isolated TAR. We compared the outcome of isolated TAR to outcomes of
      TAR with ipsilateral hindfoot arthrodesis. METHODS: In a consecutive series of
      404 primary TARs in 396 patients, 70 patients (17.3%) had a hindfoot fusion
      before, after, or at the time of TAR; the majority had either an isolated
      subtalar arthrodesis (n = 43, 62%) or triple arthrodesis (n = 15, 21%). The
      remaining 334 isolated TARs served as the control group. Mean patient follow-up
      was 3.2 years (range, 24-72 months). RESULTS: The SF-36 total, AOFAS Hindfoot
      Ankle pain subscale, Foot and Ankle Disability Index, and Short Musculoskeletal
      Function Assessment scores were significantly improved from preoperative
      measures, with no significant differences between the hindfoot arthrodesis and
      control groups. The AOFAS Hindfoot-Ankle total, function, and alignment scores
      were significantly improved for both groups, albeit the control group
      demonstrated significantly higher scores in all 3 scales. Furthermore, the
      control group demonstrated a significantly greater improvement in VAS pain score
      compared to the hindfoot arthrodesis group. Walking speed, sit-to-stand time, and
      4-square step test time were significantly improved for both groups at each
      postoperative time point; however, the hindfoot arthrodesis group completed these
      tests significantly slower than the control group. There was no significant
      difference in terms of talar component subsidence between the fusion (2.6 mm) and
      control groups (2.0 mm). The failure rate in the hindfoot fusion group (10.0%)
      was significantly higher than that in the control group (2.4%; p < 0.05).
      CONCLUSION: To our knowledge, this study represents the first series evaluating
      the clinical outcome of TARs performed with and without hindfoot fusion using
      implants available in the United States. At follow-up of 3.2 years, TAR performed
      with ipsilateral hindfoot arthrodesis resulted in significant improvements in
      pain and functional outcome; in contrast to prior studies, however, overall
      outcome was inferior to that of isolated TAR. LEVEL OF EVIDENCE: Level II,
      prospective comparative series.

PMID- 24677217
TI  - Psychometric Comparison of the PROMIS Physical Function CAT With the FAAM and FFI
      for Measuring Patient-Reported Outcomes.
AB  - BACKGROUND: Selecting optimal patient-reported outcome (PRO) instruments is
      critical to improving the quality of health care. The purpose of this study was
      to compare the reliability, responsiveness, and efficiency of three PRO measures:
      the Foot and Ankle Ability Measure-Activity of Daily Living subscale (FAAM_ADL),
      the Foot Function Index 5-point verbal rating scale (FFI-5pt), and the PROMIS
      Physical Function computerized adaptive test (PF CAT). METHODS: Data were
      aggregated from 10 clinical sites in the AOFAS's National Orthopaedic Foot and
      Ankle Research (OFAR) Network from 311 patients who underwent elective surgery
      for a disorder of the foot or ankle. Patients were administered the FAAM_ADL, FFI
      5pt, and PF CAT at their preoperative visit and at 6 months after surgery.
      Reliabilities were evaluated using a Rasch model. Responsiveness was calculated
      using paired samples t test and efficiency was recorded as number of seconds to
      complete the instrument. RESULTS: Similar reliabilities were found for the three
      instruments. Item reliabilities for FAAM_ADL, FFI-5pt, and PF CAT were all .99.
      Pearson reliabilities for FAAM_ADL, FFI-5pt, and PF CAT were .95, .93, and .96,
      respectively. On average, patients completed the FAAM_ADL in 179 seconds, the FFI
      5pt in 194 seconds, and the PF CAT in 44 seconds, ( P < .001). The PF CAT and
      FAAM_ADL showed significant improvement ( P = .01 and P = .001, respectively) in
      patients' physical function after treatment; the FFI-5pt did not show
      improvement. CONCLUSIONS: Overall, the PF CAT performed best in terms of
      reliability, responsiveness, and efficiency in this broad sample of foot and
      ankle patients. It can be a potential replacement for the conventional PRO
      measures, but further validation is needed in conjunction with the PROMIS Pain
      instruments. LEVEL OF EVIDENCE: Level I, prospective comparative outcome study.

PMID- 24677218
TI  - Calcaneocuboid Joint Subluxation After the Calcaneal Lengthening Procedure in
      Children.
AB  - BACKGROUND: We investigated radiographic changes of calcaneocuboid (CC) joint
      subluxation following calcaneal lengthening procedure for the treatment of
      pediatric planovalgus foot deformities. METHODS: This study included 44 cases of
      planovalgus foot deformities in 24 patients with mean age of 9.7 (range, 8 to 13)
      years who underwent calcaneal lengthening between 1999 and 2011. The mean follow
      up period was 25 (range, 12 to 159) months. Anteroposterior (AP) and lateral
      radiographs of the weight-bearing view of the foot from immediate postoperative,
      3-month postoperative, and last follow-up evaluations were reviewed and also used
      for trend analysis. Percentage of CC joint subluxations was measured on both AP
      and lateral view of the foot. Correlations between the percentage of CC joint
      subluxation and follow-up periods were assessed. RESULTS: All of the feet showed
      dorsal subluxation of their CC joint on the immediate postoperative lateral plain
      radiographs. The median percentage of dorsal subluxation of the CC joint improved
      from 26.0% (range, 10.0 to 67.0) at the immediate postoperative evaluation to
      16.5% (range, 7.0 to 47.0, P = .0001) at the 3-month postoperative evaluation and
      to 11% (range, 2.0 to 30.0, P = .0003) at last follow-up. The trend analysis over
      time indicated that the CC joint subluxation percentage with calcaneal
      lengthening generally decreased over time (r s = -.67, P = .001). No patients
      showed osteoarthritic changes in the CC joint or nonunion at the calcaneal
      osteotomy site at last follow-up. CONCLUSION: At midterm follow-up, the CC joint
      subluxation was gradually resolving over time, with no evidence of osteoarthritic
      change in the CC joint. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 24677219
TI  - Allograft Dermal Matrix Interpositional Arthroplasty in the Treatment of Failed
      Revision Arthrodesis at the Talonavicular Joint.

PMID- 24677220
TI  - Traumatic Dystonia: An Important Orthopaedic Differential Diagnosis.

PMID- 24677221
TI  - Appearance of Subchondral Bone in Computed Tomography Is Related to Cartilage
      Damage in Osteochondral Lesions of the Talar Dome.
AB  - BACKGROUND: Osteochondral lesions of the talar dome (OLT) involve the articular
      cartilage and/or subchondral bone. The subchondral bone plate plays an important
      role in cartilage metabolism. We hypothesized that the findings of subchondral
      bone on CT image would be related to the cartilage damage of OLT. The purpose of
      this study was to evaluate the relationship between the arthroscopic and CT
      findings focused on subchondral bone. METHODS: Thirty-one ankles diagnosed as OLT
      were analyzed. All patients underwent CT, MRI, and arthroscopic surgery. The CT
      findings for both the cystic and fragment lesions were classified into 3 types.
      The 3 types for the cystic lesion ankles were irregular shape, round shape with
      sclerotic wall, and irregular shape with opening to an articular cavity. The 3
      types for the fragment lesion were no bone absorption, bed absorption without
      fragment absorption, and bed sclerosis and fragment absorption. The subchondral
      bone findings on CT were compared with International Cartilage Repair Society
      (ICRS) grades and arthroscopic grading. RESULTS: All round and sclerotic cystic
      lesions revealed cartilaginous flap lesions with a nearly normal cartilage
      surface. An irregular shape with opening revealed an unstable lesion with
      severely damaged cartilage. As for fragment lesions, no absorption revealed a
      stable lesion with a nearly normal cartilage surface. Bed absorption revealed an
      unstable lesion with a nearly normal cartilage surface. Fragment absorption with
      bed sclerosis showed an unstable lesion with severely damaged cartilage. There
      was a significant difference between CT findings and ICRS grade or arthroscopic
      findings (both P < .01), while there was no significant difference with MRI
      grading. The diagnosis of cartilage status by CT was better than MRI. CONCLUSION:
      CT findings for OLT based on subchondral bone related to cartilage damage. This
      study showed that CT was a useful tool for evaluating cartilage damage in OLT.
      LEVEL OF EVIDENCE: Level III, comparative case series.

PMID- 24677222
TI  - Technique Tip: Avoiding Wound Complications After a Large Opening Wedge Osteotomy
      of the Distal Tibia Using a Soft-Tissue Expander.

PMID- 24677223
TI  - Factors Influencing Discharge Disposition After Ankle Arthrodesis.
AB  - BACKGROUND: Although functional and morbidity outcomes following ankle
      arthrodesis have been widely studied, patterns of health care resource
      utilization remain unclear. The purpose of this study was to identify
      preoperative and postoperative risk factors for nonroutine discharge following
      ankle arthrodesis. A secondary study aim was to determine risk factors associated
      with prolonged hospital stay. METHODS: Using the National Health Discharge Survey
      (NHDS) database for the years 2001 through 2007, an estimated 40 941 patients
      having undergone ankle arthrodesis were identified and separated into those who
      were discharged to home (routine discharge) and those who were discharged to
      rehabilitation facilities (nonroutine discharge). Factors influencing discharge
      disposition and hospital length of stay were determined using multivariable
      binary logistic regression analysis. RESULTS: Risk factors for nonroutine
      discharge were increasing age, male sex, diabetes mellitus, atrial fibrillation,
      more than 1 general or surgery-related complication, additional days of care, and
      the 2005 to 2007 time period. Risk factors associated with prolonged hospital
      stay were advanced age, female sex, diabetes mellitus, more than 1 general or
      surgery-related complication, and the 2001 to 2004 time period. CONCLUSION: Early
      identification of these factors might prove useful for better allocation of
      resources and implementation of effective strategies aimed at preventing longer
      hospitalizations and nonroutine discharges in selected patients at risk. LEVEL OF
      EVIDENCE: Level II, prognostic study.

PMID- 24677224
TI  - Susceptibility of the tick Haemaphysalis qinghaiensis to isolates of the fungus
      Metarhizium anisopliae in China.
AB  - Haemaphysalis qinghaiensis, a prevalent tick species in China, causes severe
      economic losses. In this study, we investigated the pathogenicity of six isolates
      of the fungus Metarhizium anisopliae to engorged female H. qinghaiensis using
      concentrations of 10(6), 10(7) and 10(8) conidia ml(-1). The results indicated
      that M.aAT08 and M.aAT13 isolates were highly virulent against the ticks.
      Metarhizium anisopliae has potential for biocontrol of H. qinghaiensis. 

PMID- 24677225
TI  - A simple method to determine mineralization of (14) C-labeled compounds in soil.
AB  - Degradation of organic compounds in soil is often determined by measuring the
      decrease of the parent compound and analyzing the occurrence of its metabolites.
      However, determining carbon species as end products of parent compound
      dissipation requires using labeled materials that allow more accurate
      determination of the environmental fate of the compound of interest. The current
      conventional closed system widely used to monitor degradation of (14) C-labeled
      compounds in soil is complex and expensive and requires a specialized apparatus
      and facility. In the present study, the authors describe a simple system that
      facilitates measurement of mineralization of (14) C-labeled compounds applied to
      soil samples. In the system, soda lime pellets to trap mineralized (14) C-carbon
      species, including carbon dioxide, were placed in a cup, which was then inserted
      above the treated soil sample in a tube. Mineralization of [(14) C]2,4-D applied
      to soil samples in the simple system was compared with that in the conventional
      system. The simple system provided an equivalent detection of (14) C-carbon
      species mineralized from the parent compound. The results demonstrate that this
      cost- and space-effective simple system is suitable for examining degradation and
      mineralization of (14) C-labeled compounds in soil and could potentially be used
      to investigate their mineralization in other biological matrices.

PMID- 24677226
TI  - Engaging bodies in the public imagination: bioarchaeology as social science,
      science, and humanities.
AB  - Bioarchaeology is the contextual analysis of biological remains from past
      societies. It is a young and growing discipline born during the latter half of
      the twentieth century from its roots in physical anthropology and archaeology.
      Although often associated with the study of ancient diet and disease,
      bioarchaeology leverages variable temporal scales and its global scope to provide
      a uniquely comparative perspective on human life that transcends traditional
      boundaries of the natural sciences, social sciences, and humanities. Here, we
      explore the public face of bioarchaeology and consider the trends in publication
      practices that reflect diversifying research strategies. Bioarchaeology is a
      popular topic on web-based science news aggregators. However, we identify a
      disconnect between bioarchaeology's traditional research emphases, emerging
      research foci, and findings that actually spark the public imagination. A
      majority of popular news articles emphasize basic discovery or "natural
      curiosities." Publication data indicate the field also remains regionally focused
      with relatively little emphasis on nomothetic goals. Nevertheless, bioarchaeology
      can do more to leverage its historical perspective and corporeal emphasis to
      engage a number of topics with importance across traditional academic boundaries.
      Big data, comparative, multi-investigator, interdisciplinary projects on
      violence, colonialism, and health offer the most obvious potential for driving
      research narratives in the biological and social sciences. Humanistic approaches
      that explore emotional connections to the past can also have merit. The diversity
      of research outlets and products indicates the field must embrace the importance
      of nontraditional activities in its value structure to maximize our potential in
      public arenas.

PMID- 24677227
TI  - Complications of radiologic contrast in patients with myasthenia gravis.
AB  - Use of older contrast agents during radiologic imaging in patients with
      myasthenia gravis (MG) has been associated with increased myasthenic symptoms and
      adverse drug reactions (ADRs). The effects of newer contrast agents have not been
      determined. A retrospective review of imaging safety in MG was conducted. Three
      hundred fifty-four imaging studies were analyzed. Procedures included 189
      computed tomography (CT) images with and 106 without intravenous (IV) contrast
      and 42 magnetic resonance images (MRIs) with and 17 without contrast. In 108
      patients for whom there was formal documentation of presence or absence of an
      immediate adverse response, only 1 who received CT IV contrast had an ADR (rate
      0.93%). No ADRs or weakness were reported in patients who received MRI IV
      contrast. Our data suggest there is no significant immediate increased risk of
      myasthenic weakness with the use of modern radiologic contrast agents. The rate
      of ADRs in MG patients who receive CT IV contrast is now very low (0.93%).

PMID- 24677228
TI  - Rapid awakening protocol in complex head and neck reconstruction.
AB  - BACKGROUND: Patients undergoing complex head and neck free flap reconstructions
      are commonly maintained on mechanical ventilation in an intensive care unit
      (ICU). This study reviews indications and outcomes of such patients undergoing a
      rapid awakening protocol (RAP). METHODS: We retrospectively reviewed consecutive
      patients who underwent head and neck microvascular reconstructions by a single
      surgeon between 2001 and 2013. RESULTS: Seventy-five patients underwent RAP and
      605 received mechanical ventilation. Overall complications were significantly
      higher in mechanical ventilation patients than in the RAP cohort (61% vs 31%,
      respectively; p < .001). Univariate analysis demonstrates mechanical ventilation,
      age, and aerodigestive tract involvement are significant risk factors for a
      complication and longer hospital stay. Multivariate logistic regression model
      demonstrates RAP patients had significantly less risk of a complication (odds
      ratio [OR] = 0.32; 95% [CI] = 0.19-0.54; p < .001). CONCLUSION: The recovery of
      select patients with early extubation/spontaneous breathing is superior to
      maintenance on mechanical ventilation.

PMID- 24677229
TI  - Copper-catalyzed trifluoromethylation of internal olefinic C-H bonds: efficient
      routes to trifluoromethylated tetrasubstituted olefins and N-heterocycles.
AB  - The functionalization of internal olefins has been a challenging task in organic
      synthesis. Efficient CuII-catalyzed trifluoromethylation of internal olefins,
      that is, alpha-oxoketene dithioacetals, has been achieved by using Cu(OH)2 as a
      catalyst and TMSCF3 as a trifluoromethylating reagent. The push-pull effect from
      the polarized olefin substrates facilitates the internal olefinic C-H
      trifluoromethylation. Cyclic and acyclic dithioalkyl alpha-oxoketene acetals were
      used as the substrates and various substituents were tolerated. The internal
      olefinic C-H bond cleavage was not involved in the rate-determining step, and a
      mechanism that involves radicals is proposed based on a TEMPO-quenching
      experiment of the trifluoromethylation reaction. Further derivatization of the
      resultant CF3 olefins led to multifunctionalized tetrasubstituted CF3 olefins and
      trifluoromethylated N-heterocycles.

PMID- 24677230
TI  - Enantioselective cascade Michael addition/cyclization reactions of 3-nitro-2H
      chromenes with 3-isothiocyanato oxindoles: efficient synthesis of functionalized
      polycyclic spirooxindoles.
AB  - An unprecedented Zn(OTf)2-catalyzed asymmetric Michael addition/cyclization
      cascade of 3-nitro-2H-chromenes with 3-isothiocyanato oxindoles has been
      disclosed. This transformation provides an efficient access to various
      synthetically important polycyclic spirooxindoles in a highly stereoselective
      manner under mild conditions (72-99% yields, up to >95:5 d.r. and >99% ee). The
      reaction leads to the formation of three consecutive stereocenters, including 1,3
      nonadjacent tetrasubstituted carbon stereocenters, in a single operation. A
      bifunctional activation model of the chiral Zn(OTf)2/bis(oxazoline) complex was
      proposed based on control experiments, wherein the ZnII moiety serves as a Lewis
      acid and the N atom of the free NH group acts as a Lewis base by a hydrogen
      bonding interaction.

PMID- 24677231
TI  - Targeting activated platelets and fibrinolysis: hitting two birds with one stone.

PMID- 24677232
TI  - Modifying vascular calcification in diabetes mellitus: contribution of O
      GlcNAcylation.

PMID- 24677233
TI  - Vascular niche controls organ regeneration.

PMID- 24677234
TI  - Personal reflections on big science, small science, or the right mix.

PMID- 24677235
TI  - Testing cardiovascular drug safety and efficacy in randomized trials.
AB  - Randomized trials provide the gold standard evidence on which rests the decision
      to approve novel therapeutics for clinical use. They are large and expensive and
      provide average but unbiased estimates of efficacy and risk. Concern has been
      expressed about how unrepresentative populations and conditions that pertain in
      randomized trials might be of the real world, including concerns about the
      homogeneity of the biomedical and adherence characteristics of volunteers entered
      into such trials, the dose and constancy of drug administration and the mixture
      of additional medications that are restricted in such trials but might influence
      outcome in practice. A distinction has been drawn between trials that establish
      efficacy and those that demonstrate effectiveness, drugs that patients actually
      consume in the real world for clinical benefit. However, randomized controlled
      trials remain the gold standard for establishing efficacy and the testing of
      effectiveness with less rigorous approaches is a secondary, albeit important
      consideration. Despite this, there is an appreciation that average results may
      conceal considerable interindividual variation in drug response, leading to a
      failure to appreciate clinical value or risk in subsets of patients. Thus,
      attempts are now being made to individualize risk estimates by modulating those
      derived from large randomized trials with the individual baseline risk estimates
      based on demographic and biological criteria-the individual Numbers Needed to
      Treat to obtain a benefit, such as a life saved. Here, I will consider some
      reasons why large phase 3 trials-by far the most expensive element of drug
      development-may fail to address the unmet medical needs, which should justify
      such effort and investment. 

PMID- 24677236
TI  - Thiol isomerases in thrombus formation.
AB  - Protein disulfide isomerase (PDI), ERp5, and ERp57, among perhaps other thiol
      isomerases, are important for the initiation of thrombus formation. Using the
      laser injury thrombosis model in mice to induce in vivo arterial thrombus
      formation, it was shown that thrombus formation is associated with PDI secretion
      by platelets, that inhibition of PDI blocked platelet thrombus formation and
      fibrin generation, and that endothelial cell activation leads to PDI secretion.
      Similar results using this and other thrombosis models in mice have demonstrated
      the importance of ERp5 and ERp57 in the initiation of thrombus formation. The
      integrins, alphaIIbbeta3 and alphaVbeta3, play a key role in this process and
      interact directly with PDI, ERp5, and ERp57. The mechanism by which thiol
      isomerases participate in thrombus generation is being evaluated using trapping
      mutant forms to identify substrates of thiol isomerases that participate in the
      network pathways linking thiol isomerases, platelet receptor activation, and
      fibrin generation. PDI as an antithrombotic target is being explored using
      isoquercetin and quercetin 3-rutinoside, inhibitors of PDI identified by high
      throughput screening. Regulation of thiol isomerase expression, analysis of the
      storage, and secretion of thiol isomerases and determination of the electron
      transfer pathway are key issues to understanding this newly discovered mechanism
      of regulation of the initiation of thrombus formation. 

PMID- 24677241
TI  - An experimental study on the mechanical properties of rat brain tissue using
      different stress-strain definitions.
AB  - There are different stress-strain definitions to measure the mechanical
      properties of the brain tissue. However, there is no agreement as to which stress
      strain definition should be employed to measure the mechanical properties of the
      brain tissue at both the longitudinal and circumferential directions. It is worth
      knowing that an optimize stress-strain definition of the brain tissue at
      different loading directions may have implications for neuronavigation and
      surgery simulation through haptic devices. This study is aimed to conduct a
      comparative study on different results are given by the various definitions of
      stress-strain and to recommend a specific definition when testing brain tissues.
      Prepared cylindrical samples are excised from the parietal lobes of rats' brains
      and experimentally tested by applying load on both the longitudinal and
      circumferential directions. Three stress definitions (second Piola-Kichhoff
      stress, engineering stress, and true stress) and four strain definitions (Almansi
      Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are
      used to determine the elastic modulus, maximum stress and strain. The highest non
      linear stress-strain relation is observed for the Almansi-Hamel strain definition
      and it may overestimate the elastic modulus at different stress definitions at
      both the longitudinal and circumferential directions. The Green-St. Venant strain
      definition fails to address the non-linear stress-strain relation using different
      definitions of stress and triggers an underestimation of the elastic modulus. The
      results suggest the application of the true stress-true strain definition for
      characterization of the brain tissues mechanics since it gives more accurate
      measurements of the tissue's response using the instantaneous values. 

PMID- 24677239
TI  - What can proteomics tell us about platelets?
AB  - More than 130 years ago, it was recognized that platelets are key mediators of
      hemostasis. Nowadays, it is established that platelets participate in additional
      physiological processes and contribute to the genesis and progression of
      cardiovascular diseases. Recent data indicate that the platelet proteome, defined
      as the complete set of expressed proteins, comprises >5000 proteins and is highly
      similar between different healthy individuals. Owing to their anucleate nature,
      platelets have limited protein synthesis. By implication, in patients
      experiencing platelet disorders, platelet (dys)function is almost completely
      attributable to alterations in protein expression and dynamic differences in post
      translational modifications. Modern platelet proteomics approaches can reveal (1)
      quantitative changes in the abundance of thousands of proteins, (2) post
      translational modifications, (3) protein-protein interactions, and (4) protein
      localization, while requiring only small blood donations in the range of a few
      milliliters. Consequently, platelet proteomics will represent an invaluable tool
      for characterizing the fundamental processes that affect platelet homeostasis and
      thus determine the roles of platelets in health and disease. In this article we
      provide a critical overview on the achievements, the current possibilities, and
      the future perspectives of platelet proteomics to study patients experiencing
      cardiovascular, inflammatory, and bleeding disorders. 

PMID- 24677242
TI  - Quantitative analysis of boeravinones in the roots of Boerhaavia Diffusa by
      UPLC/PDA.
AB  - INTRODUCTION: Boerhaavia diffusa is a perennial herb belonging to Nyctaginaceae.
      Various classes of chemical constituents such as phenolics (boeravinones),
      terpenoids and organic acids have been reported in B. diffusa roots. As
      boeravinones have been proposed as putative active constituents for the anti
      cancer, spasmolytic and anti-inflammatory activities exhibited by B. diffusa
      extracts, it is worthwhile developing and validating an ultra-performance liquid
      chromatography (UPLC) method for analysis of boeravinones in B. diffusa roots.
      OBJECTIVE: To develop and validate a simple, accurate, robust and rapid UPLC
      analytical method for quality control of B. diffusa roots. METHODS: Samples for
      analysis were prepared by refluxing powdered root material with methanol for 2 h.
      The extracts were concentrated, dried and stored at -20 degrees C until their
      use. A UPLC with photodiode array (PDA) method was developed and validated for
      the quantification of boeravinones in the roots of B. diffusa. The separation of
      boeravinones was achieved using a BEH Shield C18 -column (2.1 * 100 mm, 1.7 um)
      with gradient elution of methanol and water (0.1% acetic acid), at a flow rate of
      0.4 mL/min and detection was carried out at lambdamax 273 nm. RESULTS: The UPLC
      method developed showed good linearity (r(2)  >= 0.9999), accuracy and precision.
      CONCLUSION: The UPLC method developed provided a selective, sensitive and rapid
      analytical method for the quantification of boeravinones in B. diffusa roots. All
      the validation parameters were found to be within the permissible limits as per
      International Conference on Harmonisation guidelines.

PMID- 24677237
TI  - Platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling and
      vascular integrity.
AB  - Platelets are well-known for their critical role in hemostasis, that is, the
      prevention of blood loss at sites of mechanical vessel injury. Inappropriate
      platelet activation and adhesion, however, can lead to thrombotic complications,
      such as myocardial infarction and stroke. To fulfill its role in hemostasis, the
      platelet is equipped with various G protein-coupled receptors that mediate the
      response to soluble agonists such as thrombin, ADP, and thromboxane A2. In
      addition to G protein-coupled receptors, platelets express 3 glycoproteins that
      belong to the family of immunoreceptor tyrosine-based activation motif receptors:
      Fc receptor gamma chain, which is noncovalently associated with the glycoprotein
      VI collagen receptor, C-type lectin 2, the receptor for podoplanin, and Fc
      receptor gammaII A, a low-affinity receptor for immune complexes. Although both
      genetic and chemical approaches have documented a critical role for platelet G
      protein-coupled receptors in hemostasis, the contribution of immunoreceptor
      tyrosine-based activation motif receptors to this process is less defined.
      Studies performed during the past decade, however, have identified new roles for
      platelet immunoreceptor tyrosine-based activation motif signaling in vascular
      integrity in utero and at sites of inflammation. The purpose of this review is to
      summarize recent findings on how platelet immunoreceptor tyrosine-based
      activation motif signaling controls vascular integrity, both in the presence and
      absence of mechanical injury. 

PMID- 24677243
TI  - Determination of the absolute stereochemistry of two new aristophyllene
      sesquiterpenes: a combined theoretical and experimental investigation.
AB  - Aristoyunnolins G (1) and H (2), two new diastereoisomeric sesquiterpenes
      featuring a rare aristophyllene skeleton, were isolated from the traditional
      Chinese medicine Aristolochia yunnanensis. Their absolute stereochemistry
      involving three chiral centers was determined by combined chemical, spectral, and
      Density Functional Theory (DFT) calculation methods.

PMID- 24677244
TI  - Cortical bone assessed with clinical computed tomography at the proximal femur.
AB  - Hip fractures are the most serious of all fragility fractures in older people of
      both sexes. Trips, stumbles, and falls result in fractures of the femoral neck or
      trochanter, and the incidence of these two common fractures is increasing
      worldwide as populations age. Although clinical risk factors and chance are
      important in causation, the ability of a femur to resist fracture also depends on
      the size and spatial distribution of the bone, its intrinsic material properties,
      and the loads applied. Over the past two decades, clinical quantitative computed
      tomography (QCT) studies of living volunteers have provided insight into how the
      femur changes with advancing age to leave older men and women at increased risk
      of hip fractures. In this review, we focus on patterns of cortical bone loss
      associated with hip fracture, age-related changes in cortical bone, and the
      effects of drugs used to treat osteoporosis. There are several methodologies
      available to measure cortical bone in vivo using QCT. Most techniques quantify
      bone density (g/cm(3)), mass (g), and thickness (mm) in selected, predefined or
      "traditional" regions of interest such as the "femoral neck" or "total hip"
      region. A recent alternative approach termed "computational anatomy," uses
      parametric methods to identify systematic differences, before displaying
      statistically significant regions as color-scaled maps of density, mass, or
      thickness on or within a representative femur model. This review will highlight
      discoveries made using both traditional and computational anatomy methods,
      focusing on cortical bone of the proximal femur.

PMID- 24677238
TI  - Platelet lipidomics: modern day perspective on lipid discovery and
      characterization in platelets.
AB  - Lipids are diverse families of biomolecules that perform essential structural and
      signaling roles in platelets. Their formation and metabolism are tightly
      controlled by enzymes and signal transduction pathways, and their dysregulation
      leads to significant defects in platelet function and disease. Platelet
      activation is associated with significant changes to membrane lipids, and
      formation of diverse bioactive lipids plays essential roles in hemostasis. In
      recent years, new generation mass spectrometry analysis of lipids (termed
      lipidomics) has begun to alter our understanding of how these molecules
      participate in key cellular processes. Although the application of lipidomics to
      platelet biology is still in its infancy, seminal earlier studies have shaped our
      knowledge of how lipids regulate key aspects of platelet biology, including
      aggregation, shape change, coagulation, and degranulation, as well as how lipids
      generated by platelets influence other cells, such as leukocytes and the vascular
      wall, and thus how they regulate hemostasis, vascular integrity, and
      inflammation, as well as contribute to pathologies, including arterial/deep vein
      thrombosis and atherosclerosis. This review will provide a brief historical
      perspective on the characterization of lipids in platelets, then an overview of
      the new generation lipidomic approaches, their recent application to platelet
      biology, and future perspectives for research in this area. The major platelet
      regulatory lipid families, their formation, metabolism, and their role in health
      and disease, will be summarized. 

PMID- 24677245
TI  - Flexible three-axial force sensor for soft and highly sensitive artificial touch.
AB  - A soft tactile sensor able to detect both normal and tangential forces is
      fabricated with a simple method using conductive textile. Owing to the multi
      layered architecture, the capacitive-based tactile sensor is highly sensitive
      (less than 10 mg and 8 MUm, for minimal detectable weight and displacement,
      respectively) within a wide normal force range (potentially up to 27 N (400 kPa))
      and natural touch-like tangential force ranges (from about 0.5 N to 1.8 N). Being
      flexible, soft, and low cost, this sensor represents an original approach in the
      emulation of natural touch. 

PMID- 24677247
TI  - Melancholia in later life: late and early onset differences in presentation,
      course, and dementia risk.
AB  - OBJECTIVES: Depression is a risk factor for cognitive decline and dementia. This
      risk may vary with age of onset and depression subtype. Late onset depression
      (LOD, 60 years and older) is associated with more cognitive decline, whereas
      early onset depression (EOD, before 60 years) is associated with more residual
      depressive symptoms. Potential differences may reflect divergent etiologies.
      These onset differences, however, have not been examined in the melancholic
      subtype of depression in older adults. METHODS: Data were obtained from the
      Neurocognitive Outcomes of Depression in the Elderly study. Participants (N =
      284, 73% EOD-melancholic (EOD-M) and 27% LOD-melancholic (LOD-M)) were followed
      up over 3 years. Factor analyses examined differences in baseline depressive
      symptoms. Hierarchical linear growth curve models examined changes in depressive
      symptoms (Montgomery-Asberg Depression Rating Scale) and cognition (mini mental
      state examination). An annual clinical review panel assigned diagnoses of
      dementia. RESULTS: The LOD-M participants had more vegetative symptoms at
      baseline. LOD-M exhibited greater cognitive decline but fewer residual depressive
      symptoms than EOD-M. Among participants who remained in the study for at least 1
      year, in uncontrolled analyses, a greater percentage of LOD-M compared with EOD-M
      developed dementia (23.0% vs. 7.8%). Whereas in logistic analyses, controlling
      for baseline demographics, age at onset remained a predictor of dementia, the
      odds ratio suggested that the effect was relatively small. CONCLUSIONS: The EOD-M
      and LOD-M participants have a different presentation and course. LOD-M may
      represent a syndrome of neuropsychiatric deterioration with expression of both
      depressive symptoms and cognitive decline.

PMID- 24677246
TI  - Identification of the bona fide DHDPS from a common plant pathogen.
AB  - Agrobacterium tumefaciens is a Gram-negative soil-borne bacterium that causes
      Crown Gall disease in many economically important crops. The absence of a
      suitable chemical treatment means there is a need to discover new anti-Crown Gall
      agents and also characterize bona fide drug targets. One such target is
      dihydrodipicolinate synthase (DHDPS), a homo-tetrameric enzyme that catalyzes the
      committed step in the metabolic pathway yielding meso-diaminopimelate and lysine.
      Interestingly, there are 10 putative DHDPS genes annotated in the A. tumefaciens
      genome, including three whose structures have recently been determined (PDB IDs:
      3B4U, 2HMC, and 2R8W). However, we show using quantitative enzyme kinetic assays
      that nine of the 10 dapA gene products, including 3B4U, 2HMC, and 2R8W, lack
      DHDPS function in vitro. A sequence alignment showed that the product of the
      dapA7 gene contains all of the conserved residues known to be important for DHDPS
      catalysis and allostery. This gene was cloned and the recombinant product
      expressed and purified. Our studies show that the purified enzyme (i) possesses
      DHDPS enzyme activity, (ii) is allosterically inhibited by lysine, and (iii)
      adopts the canonical homo-tetrameric structure in both solution and the crystal
      state. This study describes for the first time the structure, function and
      allostery of the bona fide DHDPS from A. tumefaciens, which offers insight into
      the rational design of pesticide agents for combating Crown Gall disease.

PMID- 24677248
TI  - Adaptive defense mechanisms: function and transcendence.
AB  - This article reviews the high-adaptive (mature) defense mechanisms, along with
      case material illustrating each. These defenses are described in terms of not
      only the specific means by which they serve to ward off anxiety and manage
      conflict, but also how they often transcend their role as defenses by
      contributing to the creation of new "products" of value, such as new meanings,
      perspectives, modes of relating, and works of art or science. This report also
      discusses the implications of the use of adaptive defenses, especially humor, in
      the context of psychotherapy.

PMID- 24677249
TI  - Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation
      and hyperlipidemia.
AB  - The incidence of nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia,
      with their associated risks of endstage liver and cardiovascular diseases, is
      increasing rapidly due to the prevalence of obesity. Although the mechanisms of
      NAFLD have been studied extensively, the underlying pathogenesis and the role of
      microRNAs in this process remain relatively unclear. MicroRNA (miRNA)-dependent
      posttranscriptional gene silencing is now recognized as a key element of lipid
      metabolism. Here we report that the expression of microRNA-24 (miR-24) is
      significantly increased in the livers of high-fat diet-treated mice and in
      isolated human hepatocytes incubated with fatty acid. Knockdown of miR-24 in
      those mice caused impaired hepatic lipid accumulation and reduced plasma
      triglycerides. Bioinformatic and in vitro and in vivo studies led us to identify
      insulin-induced gene 1 (Insig1), an inhibitor of lipogenesis, as a novel target
      of miR-24. Inhibition of endogenous miR-24 expression by way of miR-24 inhibitors
      led to up-regulation of Insig1, and subsequently decreased hepatic lipid
      accumulation. It is well established that liver-specific deletion of Insig1 leads
      to higher hepatic and plasma triglyceride levels by inhibiting the processing of
      sterol regulatory element-binding proteins (SREBPs), transcription factors that
      activate lipid synthesis. As expected, miR-24 knockdown prevented SREBP
      processing, and subsequent expression of lipogenic genes. In contrast, the
      opposite result was observed with overexpression of miR-24, which enhanced SREBP
      processing. Thus, our study defines a potentially critical role for deregulated
      expression of miR-24 in the development of fatty liver by way of targeting of
      Insig1. CONCLUSION: Our findings show a novel mechanism by which miR-24 promotes
      hepatic lipid accumulation and hyperlipidemia by repressing Insig1, and suggest
      the use of miR-24 inhibitor as a potential therapeutic agent for NAFLD and/or
      atherosclerosis.

PMID- 24677250
TI  - Food and nutrition policy: a biological anthropologist's experiences from an
      academic platform.
AB  - OBJECTIVES: Biological anthropologists within academia and in other sectors are
      increasingly engaged in a variety of problem-oriented research and in the design,
      implementation, or evaluation of policies and programs, domestically and abroad.
      Such work can have distinctive requirements in terms of disciplinary background,
      professional orientation, and professional development. This article explores
      these issues through the author's autobiographical account of a career in food
      and nutrition policy from within an academic nutrition department. METHODS: The
      article is guided by an analytical framework that compares eight projects in
      terms of their mode of knowledge production, academic impact, public impacts, and
      personal rewards. The projects range from village-based surveys in Samoa and
      Malawi to food security planning in upstate New York communities, US policies on
      genetically engineered (GE) foods, and participant-observer research on nutrition
      policy development in low-income countries. RESULTS AND CONCLUSIONS: The
      cumulative experience reveals the importance of a commitment to problem-solving,
      a transdisciplinary orientation, intellectual and methodological dexterity,
      ongoing engagement with policy actors and openness to emergent research
      questions, new research settings, and nontraditional funding sources.

PMID- 24677251
TI  - Multifunctional Fe5 C2 nanoparticles: a targeted theranostic platform for
      magnetic resonance imaging and photoacoustic tomography-guided photothermal
      therapy.
AB  - Fe5 C2 NPs exhibit a high contrast in magnetic resonance imaging (MRI), superior
      photoacoustic tomography improvements, and efficient photothermal therapy (PTT)
      due to their unique core/shell structure, with a magnetic core and carbon shell.
      By conjugating a new class of affinity proteins (ZHER2:342), they can target to
      tumor cells with low cytotoxicity, and kill them through laser irritation. It is
      also possible to ablate tumors under guidance by MRI and PTT without noticeable
      side effects.

PMID- 24677252
TI  - Light harvesting and amplification of emission of donor perylene-acceptor
      perylene aggregates in aqueous medium.
AB  - With the aid of rational design, we have synthesized a pair of water-soluble
      donor- and acceptor-type twisted perylene bisimide units, which together form
      aggregates upon lowering the pH of the medium, providing bright yellow
      fluorescence. The light-harvesting efficiency of the co-assembled system can be
      tuned by controlling the ratio of donor to acceptor and 98.1 % efficiency has
      been achieved.

PMID- 24677255
TI  - Validity of maximal exercise testing in people with multiple sclerosis and low to
      moderate levels of disability.
AB  - BACKGROUND: Cardiopulmonary exercise testing can be considered the gold standard
      for assessing cardiorespiratory fitness. Little is known about the criteria for
      maximal exercise testing in people with multiple sclerosis (MS) and how these
      criteria behave across different levels of neurological disability. OBJECTIVE:
      The study objectives were to determine the criteria for maximal exercise testing
      across various levels of disability and to assess concomitant subgroup
      differences in measures related to the participant, disease, and function.
      DESIGN: This was a cross-sectional study. METHODS: Cardiopulmonary exercise
      testing was conducted with a sample of 56 participants with MS. Analysis of
      variance was used to assess the criteria in participants with MS and low, mild,
      and moderate levels of disability. RESULTS: Mean peak oxygen consumption
      (Vo2peak) was 21.4 (SD=7.1) mL.kg(-1).min(-1). An oxygen consumption (Vo2)
      plateau was seen in 37.5% of participants. A respiratory exchange ratio of 1.10
      or greater was achieved by 69.6% of the participants, a maximal heart rate within
      90% of their age-predicted maximal heart rate was achieved by 48.2% of the
      participants, and 23.2% of the participants perceived their exertion to be 18 or
      greater on the Borg Scale of Perceived Exertion (scores of 6-20). The values for
      achieved heart rate and incidence of a Vo2 plateau were significantly lower in
      participants with moderate levels of disability than in those with mild levels of
      disability. LIMITATIONS: The primary limitations of this study were its cross
      sectional nature and relatively small sample of participants with moderate levels
      of disability. CONCLUSION: The findings suggest that the outcome of
      cardiopulmonary exercise testing in people with MS and low to mild levels of
      disability (Expanded Disability Status Scale scores of <=4.0) is a valid measure
      of cardiorespiratory fitness, whereas the outcome in people with moderate levels
      of disability (Expanded Disability Status Scale scores of >4.0) is most likely
      symptom limited.

PMID- 24677253
TI  - Inlet and outlet valve flow and regurgitant volume may be directly and reliably
      quantified with accelerated, volumetric phase-contrast MRI.
AB  - PURPOSE: To determine whether it is feasible to use solely an accelerated 4D
      phase-contrast magnetic resonance imaging (4D-PC MRI) acquisition to quantify net
      and regurgitant flow volume through each of the cardiac valves. MATERIALS AND
      METHODS: Accelerated, 4D-PC MRI examinations performed between March 2010 through
      June 2011 as part of routine MRI examinations for congenital, structural heart
      disease were retrospectively reviewed and analyzed using valve-tracking
      visualization and quantification algorithms developed in Java and OpenGL.
      Excluding patients with transposition or single ventricle physiology, a total of
      34 consecutive pediatric patients (19 male, 15 female; mean age 6.9 years; age
      range 10 months to 15 years) were identified. 4D-PC flow measurements were
      compared at each valve and against routine measurements from conventional cardiac
      MRI using Bland-Altman and Pearson correlation analysis. RESULTS: Inlet and
      outlet valve net flow were highly correlated between all valves (P = 0.940
      0.985). The sum of forward flow at the outlet valve and regurgitant flow at the
      inlet valve were consistent with volumetric displacements in each ventricle (P =
      0.939-0.948). These were also highly consistent with conventional planar MRI
      measurements with net flow (P = 0.923-0.935) and regurgitant fractions (P = 0.917
      0.972) at the outlet valve and ventricular volumes (P = 0.925-0.965). CONCLUSION:
      It is possible to obtain consistent measurements of net and regurgitant blood
      flow across the inlet and outlet valves relying solely on accelerated 4D-PC. This
      may facilitate more efficient clinical quantification of valvular regurgitation.

PMID- 24677254
TI  - Are the hierarchical properties of the Fugl-Meyer assessment scale the same in
      acute stroke and chronic stroke?
AB  - BACKGROUND: The motor function section of the Fugl-Meyer assessment scale (FM
      motor scale) is a robust scale of motor ability in people after stroke, with high
      predictive validity for outcome. However, the FM motor scale is time-consuming.
      The hierarchical properties of the upper extremity (UE) and lower extremity (LE)
      sections of the FM motor scale have been established in people with chronic
      stroke. These data support the use of a more concise method of administration and
      confirm scores can be legitimately summed. OBJECTIVE: The aim of this study was
      to establish that a similar hierarchy exists in people within 72 hours after
      stroke onset. DESIGN: A prospective, cross-sectional design was used. METHODS:
      Data were obtained from 75 eligible people in a nationwide prospective study (the
      Early Prediction of Functional Outcome After Stroke). The full version of both
      sections of the FM motor scale was administered within 72 hours after stroke
      onset. The hierarchy of item difficulty was investigated by applying Guttman
      scaling procedures within each stage and each subsection of the UE and LE
      sections of the scale. The scaling procedures then were applied to item
      difficulty between stages and subsections and finally across all scale items
      (stage divisions ignored) of the FM motor scale. RESULTS: For all analyses, the
      results exceeded acceptable levels for the coefficient of reproducibility and the
      coefficient of scalability. LIMITATIONS: The sample was a population of people
      with stroke of moderate severity. CONCLUSIONS: The unidimensional hierarchy of
      the UE and LE sections of the FM motor scale (already established for chronic
      stroke) within 72 hours after stroke onset was confirmed. A legitimate total
      summed score can indicate a person's level of motor ability.

PMID- 24677256
TI  - Muscle-fat MRI: 1.5 Tesla and 3.0 Tesla versus histology.
AB  - INTRODUCTION: We evaluated muscle/fat fraction (MFF) accuracy and reliability
      measured with an MR imaging technique at 1.5 Tesla (T) and 3.0T scanner
      strengths, using biopsy as reference. METHODS: MRI was performed on muscle
      samples from pig and rabbit species (n = 8) at 1.5T and 3.0T. A chemical shift
      based 2-point Dixon method was used, collecting in-phase and out-of-phase data
      for fat/water of muscle samples. Values were compared with MFFs calculated from
      histology. RESULTS: No significant difference was found between 1.5T and 3.0T (P
      values = 0.41-0.96), or between histology and imaging (P = 0.83) for any muscle
      tested. CONCLUSIONS: RESULTS suggest that a 2-point Dixon fat/water separation
      MRI technique may provide reliable quantification of MFFs at varying field
      strengths across different animal species, and consistency was established with
      biopsy. The results set a foundation for larger scale investigation of
      quantifying muscle fat in neuromuscular disorders.

PMID- 24677257
TI  - Chiroptical phenomena in reverse micelles: the case of (1R,2S)-dodecyl (2-hydroxy
      1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB).
AB  - (1R,2S)-Dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB)
      aggregates dispersed in carbon tetrachloride have been investigated by Fourier
      transform infrared (FT-IR), vibrational circular dichroism (VCD) and (1)H nuclear
      magnetic resonance (NMR) spectroscopy at various surfactant concentration and
      water-to-surfactant molar ratio. Experimental data indicate that, even at the
      lowest investigated concentration and in absence of added water, DMEB molecules
      associate in supramolecular assemblies. At higher DMEB concentration the
      aggregates can confine water molecules, making it plausible to think that DMEB
      form reverse micelles and that water molecules are quite uniformly distributed
      among them and mainly located in the proximity of surfactant head groups.
      Moreover, the water state in DMEB reverse micelles has been found to be different
      from that in pure water, due to system-specific water/surfactant head group
      interactions. (1)H NMR diffusion measurements of both water and DMEB emphasize
      their joined translational motion characterized by a diffusion rate one order of
      magnitude lower than that of free molecules. Finally, VCD allowed us to show some
      characteristics of the association of optically active DMEB molecules as reverse
      micelles and water confinement inside; namely, we monitored the vibrational
      optical activity of deuterated hydroxyl bonds of the self-assembled DMEB
      molecules and their interaction with D(2)O molecules.

PMID- 24677258
TI  - Oral cavity anaerobic pathogens in biofilm formation on voice prostheses.
AB  - BACKGROUND: A polymerase chain reaction (PCR)-based method has been used to
      identify oral anaerobic pathogens in biofilms on voice prostheses. The purpose of
      the present study was to determine the location of those pathogens inside the
      biofilms. METHODS: Biofilms of 15 voice prostheses were sampled and used to
      identify the oral pathogens. Fluorescence in situ hybridization was applied on
      smears made on glass slides and on sections of intact biofilms visualized by
      confocal laser scanning microscopy (CLSM). RESULTS: Fusobacterium nucleatum (F.
      nucleatum) was the most frequently detected pathogen and the only tested species
      detected in microcolonies. The other microbes (Parvimonas micra [P. micra],
      Porphyromonas gingivalis [P. gingivalis], Tannerella forsythia [T. forsythia],
      and Treponema denticola [T. denticola]) were not detected or only detected as
      single cells. CLSM analysis showed that F. nucleatum resided on the biofilm
      surface. CONCLUSION: Although detectable, oral anaerobic pathogens seem to be no
      more than passers-by that adhere without further observed proliferation and
      apparently play no striking role in biofilm formation on voice prostheses.

PMID- 24677260
TI  - Winning big but feeling no better? The effect of lottery prizes on physical and
      mental health.
AB  - We use British panel data to determine the exogenous impact of income on a number
      of individual health outcomes: general health status, mental health, physical
      health problems, and health behaviours (drinking and smoking). Lottery winnings
      allow us to make causal statements regarding the effect of income on health, as
      the amount won by winners is largely exogenous. Positive income shocks have no
      significant effect on self-assessed overall health, but a significant positive
      effect on mental health. This result seems paradoxical on two levels. First,
      there is a well-known gradient in health status in cross-sectional data, and
      second, general health should partly reflect mental health, so that we may expect
      both variables to move in the same direction. We propose a solution to the first
      apparent paradox by underlining the endogeneity of income. For the second, we
      show that lottery winnings are also associated with more smoking and social
      drinking. General health will reflect both mental health and the effect of these
      behaviours and so may not improve following a positive income shock.

PMID- 24677259
TI  - Competition for food in a solitarily foraging folivorous primate (Lepilemur
      leucopus)?
AB  - Group-living folivorous primates can experience competition for food, and feeding
      competition has also been documented for solitarily foraging gummivorous and
      omnivorous primates. However, little is known about the types and consequences of
      feeding competition in solitary folivorous foragers. We conducted this study in
      the spiny forest of Berenty Reserve, southern Madagascar, to characterize the
      competitive regime of the nocturnal solitarily foraging white-footed sportive
      lemur (Lepilemur leucopus), a species that lives in dispersed pairs. We analyzed
      1,213 hr of behavioral observations recorded simultaneously for the male and
      female of each of seven social units and recorded seasonal changes in food
      availability over a complete annual cycle. Lepilemur leucopus exhibited low
      selectivity in its dietary choice and mainly included the most abundant plant
      species in its diet. Contrary to our predictions, we did not find evidence for
      increased rates of contest (i.e., displacement from food trees) or scramble
      competition (i.e., shared use of food patches) during the lean season, neither
      within nor between social units. Instead, conflict rates were low throughout the
      year, and, during these observations, any feeding stress may have been more
      related to food quality than quantity. The resource defense hypotheses may not
      explain pair-living in this species as there was no indication that males defend
      food resources for their female pair-partners. The observed lack of feeding
      competition may indicate that a cryptic anti-predator strategy is a better
      predictor of spatial avoidance of pair-partners than conflict over food. While
      anti-predator benefits of crypsis may explain, at least partly, female-female
      avoidance, studies on the relationship between territory size/quality and
      reproductive success are required to understand whether feeding competition
      reduces the potential for female association in L. leucopus.

PMID- 24677261
TI  - Organophosphate pesticides induce morphological abnormalities and decrease
      locomotor activity and heart rate in Danio rerio and Xenopus laevis.
AB  - Organophosphate pesticides (OPs), a class of acetylcholinesterase inhibitors, are
      used widely in agriculture to reduce insect populations. Because of the
      conservation of acetylcholinesterase between invertebrates and vertebrates, OPs
      also can adversely affect nontarget species, such as aquatic and terrestrial
      animals. This study used uniform conditions to analyze the morphological and
      physiological effects caused by developmental exposure to 3 commonly used OPs
      chlorpyrifos, dichlorvos, and diazinon-on 2 aquatic vertebrate species, Danio
      rerio (zebrafish) and Xenopus laevis. Survival, locomotor activity, heart rate,
      and gross anatomical abnormalities, including kyphosis and edema, were observed
      over a 5-d period in response to OP concentrations ranging from 0 uM to 1000 uM.
      Both zebrafish and Xenopus showed decreased survival for all 3 OPs at higher
      concentrations. However, Xenopus showed higher mortality than zebrafish at lower
      chlorpyrifos and dichlorvos concentrations. Both models showed a dose-dependent
      decrease in heart rate and free-swimming larval activity in response to
      chlorpyrifos and dichlorvos. In addition, kyphosis and decreased spine length
      were prominent in Xenopus in response to 10 uM of chlorpyrifos and 0.1 uM
      dichlorvos. Although diazinon induced no effects on skeletal and cardiac motor
      activity in either species, it did induce cardiac edemas in zebrafish.
      Differences in the biological actions of OPs and their differential effects in
      these 2 vertebrate models demonstrate the importance of using common protocols
      and multiple models to evaluate the ecotoxicology of OPs.

PMID- 24677262
TI  - Interaction between anions and cationic metal complexes containing tridentate
      ligands with exo-C-H groups: complex stability and hydrogen bonding.
AB  - [Re(CO)3 ([9]aneS3 )][BAr'4 ] (1), prepared by reaction of ReBr(CO)5 , 1,4,7
      trithiacyclononane ([9]aneS3 ) and NaBAr'4 , forms stable, soluble supramolecular
      adducts with chloride (2), bromide, methanosulfonate (3) and fluoride (4) anions.
      These new species were characterized by IR, NMR spectroscopy and, for 2 and 3,
      also by X-ray diffraction. The results of the solid state structure
      determinations indicate the formation of CH???X hydrogen bonds between the anion
      (X) and the exo-C?H groups of the [9]aneS3 ligand, in accord with the relatively
      large shifts found by (1) H NMR spectroscopy in dichloromethane solution for
      those hydrogens. The stability of the chloride adduct contrasts with the lability
      of the [9]aneS3 ligand in allyldicarbonyl molybdenum complexes recently studied
      by us. With fluoride, in dichloromethane solution, a second, minor neutral
      dimeric species 5 is formed in addition to 4. In 4, the deprotonation of a C?H
      group of the [9]aneS3 ligand, accompanied by C?S bond cleavage and dimerization,
      afforded 5, featuring bridging thiolates. Compounds [Mo(eta(3) -methallyl)(CO)2
      (TpyN)][BAr'4 ] (6) and [Mo(eta(3) -methallyl)(CO)2 (TpyCH)][BAr'4 ] (7) were
      synthesized by the reactions of [MoCl(eta(3) -methallyl)(CO)2 (NCMe)2 ], NaBAr'4
      and tris(2-pyridyl)amine (TpyN) or tris(2-pyridyl)methane (TpyCH) respectively,
      and characterized by IR and (1) H and (13) C NMR spectroscopy in solution, and by
      X-ray diffraction in the solid state. Compound 6 undergoes facile substitution of
      one of the 2-pyridyl groups by chloride, bromide, and methanosulfonate anions.
      Stable supramolecular adducts were formed between 7 and chloride, bromide,
      iodide, nitrate, and perrhenate anions. The solid state structures of these
      adducts (12-16) were determined by X-ray diffraction. Binding constants in
      dichloromethane were calculated from (1) H NMR titration data for all the new
      supramolecular adducts. The signal of the bridgehead C?H group is the one that
      undergoes a more pronounced downfield shift when tetrabutylammonium chloride was
      added to 7, whereas smaller shifts were found for the 2-pyridyl C(3)?H groups. In
      agreement, both types of C?H groups form hydrogen bonds to the anions in the
      solid state structures. 

PMID- 24677263
TI  - CDK1 switches mitotic arrest to apoptosis by phosphorylating Bcl-2/Bax family
      proteins during treatment with microtubule interfering agents.
AB  - Microtubule interfering agents (MIAs), that can stabilise or depolymerise
      microtubules, are an important class of cancer chemotherapeutic drugs. They can
      lead to mitotic arrest and subsequent apoptosis. We demonstrate that cell cycle
      dependent kinase 1 (CDK1) is important in switching cells from mitotic arrest to
      apoptosis during MIAs treatment. Overexpression of non-degradable cyclin B1
      sustained CDK1 activation and mitotic arrest, followed by caspase-3 dependent
      apoptosis. CDK1 is responsible for the phosphorylation of several pro- and anti
      apoptotic Bcl-2 family proteins during MIAs treatment. CDK1-mediated Bcl-2 serine
      70 phosphorylation enhances its pro-apoptotic function, whereas CDK1-mediated Bad
      serine 128 phosphorylation promotes apoptosis. Blockage of CDK1 activity with a
      specific pharmacological inhibitor suppresses Mcl-1 phosphorylation, degradation
      and its anti-apoptotic function. Therefore, the death of cancer cells under MIAs
      treatment was caused by imbalance between CDK1-induced alterations in the pro
      apoptotic and anti-apoptotic functions of phosphorylated Bcl-2 family proteins. 

PMID- 24677264
TI  - Marrying kin in small-scale societies.
AB  - OBJECTIVES: Marriages among kin have the dual effect of both increasing average
      group relatedness as well as reducing the total number of kin by eliminating more
      genealogically and geographically distant individuals from kinship networks.
      Marriage decisions therefore face a tradeoff between density of kin, or formation
      of intensive kinship systems, and the diversity of kin, or extensive kinship
      systems. This article tests the hypothesis that extensive kinship systems best
      characterize hunter-gatherer societies, whereas more intensive forms of
      subsistence, like horticultural, agricultural, and pastoral economies, are more
      likely to have intensive kinship systems. METHODS: Here, we investigate the wide
      range of variation in prevalence of kin marriages across a sample of 46 small
      scale societies, split evenly between hunter-gatherers and agropastoralists
      (including horticulturalists), using genealogies that range in depth from 4 to 16
      generations. Regression methods examine how subsistence and polygyny relate to
      spousal relatedness and inbreeding across societies. RESULTS: On average, hunter
      gatherers show limited numbers of kin marriages and low levels of inbreeding,
      whereas some agropastoralists are characterized by much higher levels of both,
      especially in societies where polygynous marriages are more common. CONCLUSION:
      Intensive kinship systems emerge in some intensive economies. This pattern may
      have favored a kin-selected increase in more large-scale cooperation and
      inequality occurring relatively recently in human history after the advent of
      domesticated plants and animals.

PMID- 24677267
TI  - NMR structures of fusion peptide from influenza hemagglutinin H3 subtype and its
      mutants.
AB  - The influenza fusion peptide located at the N-terminus of the hemagglutinin HA2
      subunit initiates the fusing process of the viral membrane with the host cell
      endosomal membrane. It had been reported that the structure of a 20-residue H3
      subtype fusion peptide (H3-HAfp20) was significantly different with that of a H1
      subtype 23-residue one (H1-HAfp23). The sequential difference between the 12th
      and 15th residues of H1 and H3 subtypes could not fully explain the
      conformational variation. The first and last three amino acids of H3-HAfp23
      involved in formation of hydrogen bonds may play an important role in fusion
      process. To confirm this hypothesis, we investigate the structures of H3-HAfp23
      peptide and its mutants, G1S and G1V, in dodecylphosphatidyl choline micelles by
      using heteronuclear NMR technology. The results demonstrate that, similar to H1
      HAfp23 but significantly different with H3-HAfp20, H3-HAfp23 also has tight
      helical hairpin structure with the N- and C-terminuses linked together because of
      the hydrogen bonds between Gly1 and the last three amino acids, Trp21--Tyr22-
      Gly23. Although the 'hemifusion' G1S and lethal G1V mutants have hairpin-like
      helical structures, the distances between the N- and C-terminuses are increased
      as shortage of the hydrogen bonds and the larger kink angle between the
      antiparallel helices. The paramagnetic ion titration experiments show that the
      terminuses are inserted into the dodecylphosphatidyl choline micelles used as
      solving media. These may imply that the tight helical hairpin structure,
      especially the closed conformation at terminus, plays an important role in fusion
      activity.

PMID- 24677266
TI  - Talin-driven inside-out activation mechanism of platelet alphaIIbbeta3 integrin
      probed by multimicrosecond, all-atom molecular dynamics simulations.
AB  - Platelet aggregation is the consequence of the binding of extracellular bivalent
      ligands such as fibrinogen and von Willebrand factor to the high affinity, active
      state of integrin alphaIIbbeta3. This state is achieved through a so-called
      "inside-out" mechanism characterized by the membrane-assisted formation of a
      complex between the F2 and F3 subdomains of intracellular protein talin and the
      integrin beta3 tail. Here, we present the results of multi-microsecond, all-atom
      molecular dynamics simulations carried on the complete transmembrane (TM) and C
      terminal (CT) domains of alphaIIbbeta3 integrin in an explicit lipid-water
      environment, and in the presence or absence of the talin-1 F2 and F3 subdomains.
      These large-scale simulations provide unprecedented molecular-level insights into
      the talin-driven inside-out activation of alphaIIbbeta3 integrin. Specifically,
      they suggest a preferred conformation of the complete alphaIIbbeta3 TM/CT domains
      in a lipid-water environment, and testable hypotheses of key intermolecular
      interactions between alphaIIbbeta3 integrin and the F2/F3 domains of talin-1.
      Notably, not only do these simulations give support to a stable left-handed
      reverse turn conformation of the alphaIIb juxtamembrane motif rather than a
      helical turn, but they raise the question as to whether TM helix separation is
      required for talin-driven integrin activation.

PMID- 24677265
TI  - METTL21C is a potential pleiotropic gene for osteoporosis and sarcopenia acting
      through the modulation of the NF-kappaB signaling pathway.
AB  - Sarcopenia and osteoporosis are important public health problems that occur
      concurrently. A bivariate genome-wide association study (GWAS) identified
      METTL21c as a suggestive pleiotropic gene for both bone and muscle. The METTL21
      family of proteins methylates chaperones involved in the etiology of both
      myopathy and inclusion body myositis with Paget's disease. To validate these GWAS
      results, Mettl21c mRNA expression was reduced with siRNA in a mouse myogenic
      C2C12 cell line and the mouse osteocyte-like cell line MLO-Y4. At day 3, as C2C12
      myoblasts start to differentiate into myotubes, a significant reduction in the
      number of myocytes aligning/organizing for fusion was observed in the siRNA
      treated cells. At day 5, both fewer and smaller myotubes were observed in the
      siRNA-treated cells as confirmed by histomorphometric analyses and immunostaining
      with myosin heavy chain (MHC) antibody, which only stains myocytes/myotubes but
      not myoblasts. Intracellular calcium (Ca(2+)) measurements of the siRNA-treated
      myotubes showed a decrease in maximal amplitude peak response to caffeine,
      suggesting that less Ca(2+) is available for release due to the partial silencing
      of Mettl21c, correlating with impaired myogenesis. In siRNA-treated MLO-Y4 cells,
      48 hours after treatment with dexamethasone there was a significant increase in
      cell death, suggesting a role of Mettl21c in osteocyte survival. To investigate
      the molecular signaling machinery induced by the partial silencing of Mettl21c,
      we used a real-time PCR gene array to monitor the activity of 10 signaling
      pathways. We discovered that Mettl21c knockdown modulated only the NF-kappaB
      signaling pathway (ie, Birc3, Ccl5, and Tnf). These results suggest that Mettl21c
      might exert its bone-muscle pleiotropic function via the regulation of the NF
      kappaB signaling pathway, which is critical for bone and muscle homeostasis.
      These studies also provide rationale for cellular and molecular validation of
      GWAS, and warrant additional in vitro and in vivo studies to advance our
      understanding of role of METTL21C in musculoskeletal biology.

PMID- 24677268
TI  - The double burden of age and disease on cognition and quality of life in bipolar
      disorder.
AB  - OBJECTIVE: Bipolar disorder (BPD) and normal aging are known to impact cognitive
      skills and health-related quality of life (HRQOL). This study investigated how
      aging and disease interact in predicting cognitive and psychosocial outcomes.
      METHODS: Eight cognitive and ten subjective HRQOL domain ratings were measured.
      Subjects included 80 young (18-29 years) and late middle-aged (50-65 years) BPD
      patients in the euthymic phase and 70 age-equivalent healthy comparison
      participants. RESULTS: An age X disease interaction was detected in three domains
      of cognitive functioning that reflect emotion processing, processing speed, and
      executive functioning skills, with BPD patients in the older group performing
      most poorly. There was a double burden of aging and disease on reported ability
      to perform physical tasks. However, regardless of age, disease status was
      associated with lower ratings of HRQOL in the psychosocial/affective sphere and
      the majority of cognitive domains. Post hoc analyses revealed that number of
      years ill was positively associated with select HRQOL ratings in older, but not
      younger BPD adults. CONCLUSIONS: These findings may stimulate future longitudinal
      study of cognition and quality of life in BPD patients across the life span,
      focusing on additive and interactive effects of aging and disease burden, which
      could culminate in developing more effective treatment and rehabilitation
      strategies for this traditionally challenging to treat population.

PMID- 24677269
TI  - Effect of mixed layer crystallinity on the performance of mixed heterojunction
      organic photovoltaic cells.
AB  - Organic vapor-phase deposition (OVPD) is used to grow
      tetraphenyldibenzoperiflanthen (DBP):C70 mixed heterojunction photovoltaic
      devices. Compared with vacuum thermal evaporation (VTE), the OVPD-grown film
      develops nanocrystalline domains of C70. Optimized OVPD-grown OPVs have a 61%
      fill factor for a 100 nm active layer thickness, whereas VTE-grown devices have a
      47% fill factor at the same thickness.

PMID- 24677270
TI  - Incorporation of Rician noise in the analysis of biexponential transverse
      relaxation in cartilage using a multiple gradient echo sequence at 3 and 7 Tesla.
AB  - PURPOSE: Previous work has evaluated the quality of different analytic methods
      for extracting relaxation times from magnitude imaging data exhibiting Rician
      noise. However, biexponential analysis of relaxation in tissue, including
      cartilage, and materials is of increasing interest. We, therefore, analyzed
      biexponential transverse relaxation decay in the presence of Rician noise and
      assessed the accuracy and precision of several approaches to determining
      component fractions and apparent transverse relaxation times. THEORY AND METHODS:
      Comparisons of four different voxel-by-voxel fitting methods were performed using
      Monte Carlo simulations, and phantom and ex vivo bovine nasal cartilage (BNC)
      experiments. In each case, preclinical and clinical imaging field strengths of 7
      Tesla (T) and 3T, respectively, and parameters, were investigated across a range
      of signal-to-noise ratios (SNR). Results were compared with Cramer-Rao lower
      bound calculations. RESULTS: As expected, at high SNR, all methods performed
      well. At lower SNR, fits explicitly incorporating the analytic form of the Rician
      noise maintained performance. The much more efficient correction scheme of
      Gudbjartsson and Patz performed almost as well in many cases. Ex vivo experiments
      on phantoms and BNC were consistent with simulation results. CONCLUSION: Explicit
      incorporation of Rician noise greatly improves accuracy and precision in the
      analysis of biexponential transverse decay data.

PMID- 24677272
TI  - Tunable, ultralow-power switching in memristive devices enabled by a
      heterogeneous graphene-oxide interface.
AB  - Memristive devices based on vertical heterostructures of graphene and TiOx show a
      significant power reduction that is up to ~10(3) times smaller than that of
      conventional structures. This power reduction arises as a result of a tunneling
      barrier at the interface. The barrier is tunable, opening up the possibility of
      engineering several key memory characteristics. 

PMID- 24677271
TI  - Induction of atherosclerosis in mice and hamsters without germline genetic
      engineering.
AB  - RATIONALE: Atherosclerosis can be achieved in animals by germline genetic
      engineering, leading to hypercholesterolemia, but such models are constrained to
      few species and strains, and they are difficult to combine with other powerful
      techniques involving genetic manipulation or variation. OBJECTIVE: To develop a
      method for induction of atherosclerosis without germline genetic engineering.
      METHODS AND RESULTS: Recombinant adeno-associated viral vectors were engineered
      to encode gain-of-function proprotein convertase subtilisin/kexin type 9 mutants,
      and mice were given a single intravenous vector injection followed by high-fat
      diet feeding. Plasma proprotein convertase subtilisin/kexin type 9 and total
      cholesterol increased rapidly and were maintained at high levels, and after 12
      weeks, mice had atherosclerotic lesions in the aorta. Histology of the aortic
      root showed progression of lesions to the fibroatheromatous stage. To demonstrate
      the applicability of this method for rapid analysis of the atherosclerosis
      susceptibility of a mouse strain and for providing temporal control over disease
      induction, we demonstrated the accelerated atherosclerosis of mature diabetic
      Akita mice. Furthermore, the versatility of this approach for creating
      atherosclerosis models also in nonmurine species was demonstrated by inducing
      hypercholesterolemia and early atherosclerosis in Golden Syrian hamsters.
      CONCLUSIONS: Single injections of proprotein convertase subtilisin/kexin type 9
      encoding recombinant adeno-associated viral vectors are a rapid and versatile
      method to induce atherosclerosis in animals. This method should prove useful for
      experiments that are high-throughput or involve genetic techniques, strains, or
      species that do not combine well with current genetically engineered models.

PMID- 24677274
TI  - The effect of noncognitive traits on health behaviours in adolescence.
AB  - This paper investigates the relationship between personality traits and health
      behaviours in adolescence using a large and recent cohort study. In particular,
      we investigate the impact of locus of control, self-esteem and work ethics at
      ages 15-16 years on the incidence of health behaviours such as alcohol
      consumption, cannabis and other drug use, unprotected and early sexual activity
      and sports and physical activity. We use matching methods to control for a very
      rich set of adolescent and family characteristics, and we find that personality
      traits do affect health behaviours. In particular, individuals with external
      locus of control, low self-esteem or with low levels of work ethics seem more
      likely in engage in risky health behaviours.

PMID- 24677273
TI  - Activin A immunoexpression as predictor of occult lymph node metastasis and
      overall survival in oral tongue squamous cell carcinoma.
AB  - BACKGROUND: The presence of regional lymph node metastasis has an important
      impact on clinical management and prognostication of patients with oral tongue
      squamous cell carcinoma (SCC). Approximately 30% to 50% of patients with oral
      tongue SCC have regional metastasis at diagnosis, but the limited sensibility of
      the current diagnostic methods used for neck staging does not allow detection of
      all cases, leaving a significant number of undiagnosed metastasis (occult lymph
      node metastasis). In this study, we evaluated whether clinicopathologic features
      and immunohistochemical detection of carcinoma-associated fibroblasts (CAFs) and
      activin A could be predictive markers for occult lymph node metastasis in oral
      tongue SCC. METHODS: One hundred ten patients with primary oral tongue SCC, who
      were classified with early stage tumor (stage I and II) and received surgical
      treatment with elective neck dissection, were enrolled in the study. RESULTS:
      Among all examined features, only high immunohistochemical expression of activin
      A was significantly associated with presence of occult lymph node metastasis (p =
      .006). Multivariate survival analysis using the Cox proportional hazard model
      showed that the expression of activin A was an independent marker of reduced
      overall survival with a 5-year survival of 89.7% for patients with low expression
      compared to 76.5% for those with high expression (hazard ratio [HR], 2.44; 95%
      confidence interval [CI], 1.55-3.85; p = .012). CONCLUSION: Our results
      demonstrated that immunodetection of activin A can be useful for prognostication
      of oral tongue SCC, revealing patients with occult lymph node metastasis and
      lower overall survival.

PMID- 24677275
TI  - One-pot synthesis of highly luminescent carbon quantum dots and their nontoxic
      ingestion by zebrafish for in vivo imaging.
AB  - Photoluminescent carbon and/or silicon-based nanodots have attracted ever
      increasing interest. Accordingly, a myriad of synthetic methodologies have been
      developed to fabricate them, which unfortunately, however, frequently involve
      relatively tedious steps, such as initial surface passivation and subsequent
      functionalization. Herein, we describe a green and sustainable synthetic strategy
      to combine these procedures into one step and to produce highly luminescent
      carbon quantum dots (CQDs), which can also be easily fabricated into flexible
      thin films with intense luminescence for future roll-to-roll manufacturing of
      optoelectronic devices. The as-synthesized CQDs exhibited enhanced cellular
      permeability and low or even noncytotoxicity for cellular applications, as
      corroborated by confocal fluorescence imaging of HeLa cells as well as cell
      viability measurements. Most strikingly, zebrafish were directly fed with CQDs
      for in vivo imaging, and mortality and morphologic analysis indicated ingestion
      of the CQDs posed no harm to the living organisms. Hence, the multifunctional
      CQDs potentially provide a rich pool of tools for optoelectronic and biomedical
      applications. 

PMID- 24677276
TI  - Computational ECD spectrum simulation of the phytotoxin scytalone: importance of
      solvent effects on conformer populations.
AB  - A time-dependent Density Functional Theory (TDDFT) computational simulation of
      the electronic circular dichroism (ECD) spectrum of the phytotoxin scytalone (1),
      produced by different plant pathogenic fungi and involved in melanin production,
      was undertaken with the aim to establish a nonempirical correlation between the
      spectrum and the absolute configuration of this compound. In fact, very low
      optical rotation data of do not afford a reliable absolute configuration
      assignment while, on the contrary, the use of ECD can provide a useful tool for
      its stereochemical description. This structurally simple molecule displayed a
      considerable molecular flexibility, which made it mandatory to obtain an accurate
      conformers distribution to get a good reproduction of the experimental ECD
      spectrum. Only the application of an implicit integral equation formalism
      Polarizable Continuum Model (IEF-PCM) solvation model in the calculations allowed
      us to properly describe the conformer populations and finally obtain a more than
      satisfactory spectral simulation.

PMID- 24677278
TI  - Effects of titanium dioxide (TiO2 ) nanoparticles on caribbean reef-building
      coral (Montastraea faveolata).
AB  - Increased use of manufactured titanium dioxide nanoparticles (nano-TiO2 ) is
      causing a rise in their concentration in the aquatic environment, including coral
      reef ecosystems. Caribbean mountainous star coral (Montastraea faveolata) has
      frequently been used as a model species to study gene expression during stress
      and bleaching events. Specimens of M. faveolata were collected in Panama and
      exposed for 17 d to nano-TiO2 suspensions (0.1 mg L(-1) and 10 mg L(-1) ).
      Exposure to nano-TiO2 caused significant zooxanthellae expulsion in all the
      colonies, without mortality. Induction of the gene for heat-shock protein 70
      (HSP70) was observed during an early stage of exposure (day 2), indicating acute
      stress. However, there was no statistical difference in HSP70 expression on day 7
      or 17, indicating possible coral acclimation and recovery from stress. No other
      genes were significantly upregulated. Inductively coupled plasma mass
      spectrometry analysis revealed that nano-TiO2 was predominantly trapped and
      stored within the posterior layer of the coral fragment (burrowing sponges,
      bacterial and fungal mats). The bioconcentration factor in the posterior layer
      was close to 600 after exposure to 10 mg L(-1) of nano-TiO2 for 17 d. The
      transient increase in HSP70, expulsion of zooxanthellae, and bioaccumulation of
      nano-TiO2 in the microflora of the coral colony indicate the potential of such
      exposure to induce stress and possibly contribute to an overall decrease in coral
      populations.

PMID- 24677279
TI  - Personality and subjective well-being in captive male western lowland gorillas
      living in bachelor groups.
AB  - The purpose of this study was to determine the personality structure of eight
      male gorillas (five silverbacks and three blackbacks) housed at the Sedgwick
      County Zoo in Wichita, Kansas and to determine if personality predicts behavior
      and subjective well-being in male gorillas living in bachelor groups. We used the
      Hominoid Personality Questionnaire which contains 54 descriptive adjectives with
      representative items from the human five-factor model. Rates of 12 behaviors that
      are broadly defined as agonistic or affiliative were independently recorded and
      calculated. Principal components analysis yielded three reliable personality
      factors: Dominance, Extraversion/Agreeableness, and Conscientiousness. These
      results are the first potential quantitative evidence for a Conscientiousness
      factor in a hominoid other than chimpanzees and humans. This suggests that
      Conscientiousness originated with the common ancestor of male gorillas and humans
      around 10 million years ago. These results indicate that humans can reliably
      assess the personality and subjective well-being of captive male gorillas living
      in bachelor groups with robust levels of inter-rater reliability and validity.
      Furthermore, personality can accurately predict behavior (r = 0.79; n = 13) and
      subjective well-being (r = 0.83; n = 5) in gorillas and provide convergent and
      discriminant validity for the personality factors. The results advocate for the
      use of personality questionnaires in the captive management of bachelor gorillas
      over long-term multi-institutional behavioral studies.

PMID- 24677277
TI  - Bone metabolism after bariatric surgery.
AB  - Bariatric surgery is a popular and effective treatment for severe obesity but may
      have negative effects on the skeleton. This review summarizes changes in bone
      density and bone metabolism from animal and clinical studies of bariatric
      surgery, with specific attention to Roux-en-Y gastric bypass (RYGB), adjustable
      gastric banding (AGB), and sleeve gastrectomy (SG). Skeletal imaging artifacts
      from obesity and weight loss are also considered. Despite challenges in bone
      density imaging, the preponderance of evidence suggests that bariatric surgery
      procedures have negative skeletal effects that persist beyond the first year of
      surgery, and that these effects vary by surgical type. The long-term clinical
      implications and current clinical recommendations are presented. Further study is
      required to determine mechanisms of bone loss after bariatric surgery. Although
      early studies focused on calcium/vitamin D metabolism and mechanical unloading of
      the skeleton, it seems likely that surgically induced changes in the hormonal and
      metabolic profile may be responsible for the skeletal phenotypes observed after
      bariatric surgery.

PMID- 24677280
TI  - Low-LUMO pyrene-fused azaacenes.
AB  - A series of pyrene-fused azaacenes with four and six linearly fused rings that
      possess LUMO levels between -3.7 and -4.3 eV is reported. These LUMO values are
      remarkably lower than those typically observed for pyrene-fused azaacenes, even
      for systems with sixteen linearly fused rings, and are comparable to those
      observed for state-of-the-art n-azaacenes. 

PMID- 24677281
TI  - Shape selectivity by guest-driven restructuring of a porous material.
AB  - A flexible metal-organic framework selectively sorbs para- (pX) over meta-xylene
      (mX) by synergic restructuring around pX coupled with generation of unused void
      space upon mX loading. The nature of the structural change suggests more
      generally that flexible structures which are initially mismatched in terms of fit
      and capacity to the preferred guest are strong candidates for effective molecular
      separations. 

PMID- 24677282
TI  - Mindfulness-based stress reduction for older adults with worry symptoms and co
      occurring cognitive dysfunction.
AB  - BACKGROUND: Mindfulness-based stress reduction (MBSR) has the potential to reduce
      worry and improve cognitive functioning. OBJECTIVES: In this treatment
      development project, we examined MBSR in older adults with worry symptoms and co
      occurring cognitive dysfunction. We examined (i) acceptability of MBSR, (ii)
      whether MBSR needs to be lengthened providing more repetition, (iii) MBSR's
      benefits for worry reduction and cognitive improvements, and (iv) continued use
      of MBSR techniques during follow-up. METHODS: Two sites (St. Louis and San Diego)
      enrolled individuals aged 65 years or older with significant anxiety-related
      distress plus subjective cognitive dysfunction, into traditional 8-session MBSR
      groups and 12-session groups that had the same content but more repetition of
      topics and techniques. We examined measures of mindfulness, worry, and a
      neuropsychological battery focused on memory and executive function before and
      after the MBSR program, and we followed up participants for 6 months after the
      completion of MBSR regarding their continued use of its techniques. RESULTS:
      Participants (N = 34) showed improvements in worry severity, increases in
      mindfulness, and improvements in memory as measured by paragraph learning and
      recall after a delay, all with a large effect size. Most participants continued
      to use MBSR techniques for 6 months post-instruction and found them helpful in
      stressful situations. There was no evidence that the extended 12-week MBSR
      produced superior cognitive or clinical outcomes, greater satisfaction, or
      greater continuation of MBSR techniques than 8-week MBSR. CONCLUSIONS: These
      preliminary findings are promising for the further testing and use of MBSR in
      older adults suffering from clinical worry symptoms and co-occurring cognitive
      dysfunction. These are common problems in a broad range of older adults, many of
      whom have anxiety and mood disorders; therefore, stress reduction intervention
      for them may have great public health value.

PMID- 24677284
TI  - Differentiating white matter lesions in multiple sclerosis and migraine using
      monoexponential and biexponential diffusion measurements.
AB  - PURPOSE: To compare the white matter lesions seen in multiple sclerosis and
      migraine using monoexponential and high b-value biexponential diffusion
      measurements. MATERIALS AND METHODS: Diffusion-weighted images were acquired on a
      3.0-Tesla magnetic resonance imaging system. Diffusion parameters were estimated
      using monoexponential (0-1000 s/mm(2) ) and biexponential (0-5000 s/mm(2) )
      approaches from 15 multiple sclerosis patients, 15 patients with migraine and 15
      healthy control subjects. The study was performed in accordance with the approval
      of the Regional Research Ethics Committee. The apparent diffusion coefficient
      (ADC) values were measured in the lesions and the normal-appearing white matter
      of patients and in the white matter of controls. RESULTS: High lesional ADCmono
      values were detected in both patient groups without significant differences
      between the groups (10.72 and 9.86 * 10(-4) mm(2) /s for MS and migraine
      respectively, P = 0.2134). The biexponential measurements showed significantly
      higher ADCfast , ADCslow , and Pslow values in the migraine lesions than in the
      multiple sclerosis lesions (16.47 versus 14.29, 1.41 versus 0.76, and 20.34
      versus 12.01 all values in 10(-4) mm(2) /s; P = 0.0344, P = 0.0019, P = 0.0021,
      respectively). CONCLUSION: Biexponential diffusion analysis may help to
      differentiate multiple sclerosis-related white matter lesions from migraine
      related ones.

PMID- 24677285
TI  - An intelligent superwetting PVDF membrane showing switchable transport
      performance for oil/water separation.
AB  - A superamphiphilic poly(vinylidene fluoride) (PVDF) membrane with
      superoleophobicity under water and superhydrophobicity under oil is successfully
      prepared. Due to the switchable transport performance, the membrane is applicable
      to the separation of various oil-in-water and water-in-oil emulsions with a
      droplet size greater than 20 nm, and shows superior permeability and antifouling
      properties, as well as a high separation efficiency. 

PMID- 24677283
TI  - Surgical treatment for recurrent solitary fibrous tumor invading atlas.
AB  - BACKGROUND: Solitary fibrous tumor (SFT), a rare neoplasm, usually originates in
      the pleura. Extrapleural SFTs occasionally occur in the head and neck. METHODS:
      In this study, the extirpation of a rare case of recurrent SFT invading the atlas
      is discussed. RESULTS: Ten years after surgical resection of an SFT in the right
      parapharyngeal space, the patient returned with a complaint of swelling sensation
      in the right neck. MRI and CT showed an enhanced lobulated mass invading the
      right lateral C1 vertebral body and canal and encasing the right vertebral
      artery. Extirpation of the recurrent tumor with a combined transcervical and
      midline posterior approach was successful. The surgical margin was negative for
      cancer and the postoperative course was uneventful. CONCLUSION: Although an SFT
      is generally benign, recurrence can occur even after several years, therefore,
      careful long-term follow-up is essential for early detection. A combined
      transcervical and midline posterior approach proved useful for resection of the
      atlas body.

PMID- 24677286
TI  - Anhydrous lanthanide MOFs and direct photoluminescent sensing for
      polyoxometalates in aqueous solution.
AB  - New anhydrous lanthanide metal-organic frameworks (MOFs) [Pr(tip)1.5]2n (tip-Pr),
      [Nd(tip)1.5]2n (tip-Nd), [Eu-(tip)1.5]2n (tip-Eu), and [Eu(OH)(mip)]n (mip-Eu)
      (tip=5-tert-butylisophthalate anion, mip=5-methylisophthalate ion), have been
      hydrothermally synthesized and structurally characterized by elemental analyses,
      FT-IR spectroscopy, single-crystal X-ray diffraction, thermal gravimetric
      analysis/differential thermal analysis (TG/DTA), and X-ray powder diffraction
      (XRPD) techniques. MOFs tip-Pr, tip-Nd, and tip-Eu are isostructural anhydrous
      compounds, and exhibit an unprecedented 3D microporous structure with hexagonal
      channel arrays. The selectively prepared MOF mip-Eu presents an interpenetrated
      3D microporous architecture containing the hydroxyl cluster chains. Solid-state
      photoluminescence properties at room temperature indicate that both tip-Eu and
      mip-Eu display the characteristic of the Eu3+ ion spectrum dominated by the 5D0-
      >7F(J) (J=0-4) transition. Compared with mip-Eu, tip-Eu displays the very high
      solid-state quantum yield (0.62 +/- 0.03) and longer lifetime value (0.94 +/-
      0.01 ms), which is due to the absence of the hydroxyl groups from the solid-state
      structure of tip-Eu. More importantly, a new method to directly investigate the
      potential of solid-state lanthanide MOFs for ionic sensing in aqueous solutions
      has been developed, and successfully applied it to study the potential sensing
      function of tip-Eu for polyoxometalates (POMs). The possible mechanism for the
      quenching effect of POMs on the fluorescence of tip-Eu is elucidated by the
      strongly competitive absorption of the excited light source energy between POMs
      and tip ligands. The very promise for the highly sensitive sensing for
      polyoxometalates, together with the characteristic of the reversible fluorescence
      response, suggest that solid-state tip-Eu can be an excellent candidate for the
      directly photoluminescent detection of POMs in aqueous solutions.

PMID- 24677287
TI  - Novel cleavable cell-penetrating peptide-drug conjugates: synthesis and
      characterization.
AB  - We report the first drug conjugate with a negatively charged amphipathic cell
      penetrating peptide. Furthermore, we compare two different doxorubicin cell
      penetrating peptide conjugates, which are both unique in their properties, due to
      their net charge at physiological pH, namely the positively charged octaarginine
      and the negatively charged proline-rich amphipathic peptide. These conjugates
      were prepared exploiting a novel heterobifunctional crosslinker to join the N
      terminal cysteine residue of the peptides with the aliphatic ketone of
      doxorubicin. This small linker contains an activated thiol as well as aminooxy
      functionality, capable of generating a stable oxime bond with the C-13 carbonyl
      group of doxorubicin. The disulfide bond formed between the peptide and
      doxorubicin enables the release of the drug in the cytosol, as confirmed by drug
      release studies performed in the presence of glutathione. Additionally, the
      cytotoxicity as well as the cellular uptake and distribution of this tripartite
      drug delivery system was investigated in MCF-7 and HT-29 cell lines.

PMID- 24677288
TI  - X-linked hypophosphatemic rickets: enamel abnormalities and oral clinical
      findings.
AB  - X-linked hypophosphatemia (XLH) is a genetic disorder related to alterations in
      bones and teeth formation, due to low levels of phosphate in blood. Oral findings
      in XLH have been enamel and dentine abnormalities, high pulp horns, large pulp
      chambers, and some cases of periapical abscesses related to teeth without caries
      or traumatic injuries. The aim of our study was to assess the presence of enamel
      alterations, such as microclefts and/or structure defects in patients with XLH
      and give guidelines of prevention of XLH dental complications. History taking,
      oral clinical and radiological examination in 10 young patients affected by XLH
      (average age of 9) and in 6 patients without XLH (average age of 8). Impressions
      were performed on the vestibular surfaces of teeth in order to obtain replicas.
      The replicas were analyzed using scanning electron microscope (SEM) and compared
      to replicas of control group. The images of replicas of XLH patients showed deep
      microclefts and irregular enamel surface structure compared to replicas of
      control group. The replica of a patient with spontaneous periapical abscesses
      showed numerous enamel crater-shaped depressions and deep microcleavages
      penetrating into the enamel thickness. In absence of caries or fractures, the
      abscesses pathogenesis may be related to microcleavages of the enamel and dentin,
      which allow bacterial invasion of the pulp. There could be a relationship between
      XLH disease and enamel abnormalities.

PMID- 24677289
TI  - Cost-effectiveness analysis and insurance coverage: solving a puzzle.
AB  - The conventional model for the use of cost-effectiveness analysis for health
      programs involves determining whether the cost per unit of effectiveness of the
      program is lower than some socially determined maximum acceptable cost per unit
      of effectiveness. If a program is better by this criterion, the policy
      implication is that it should be implemented by full coverage of its cost by
      insurance; if not, the program should not be implemented. This paper examines the
      unanswered question of how cost-effectiveness analysis should be performed and
      interpreted when insurance coverage may involve cost sharing. It explores the
      question of how cost sharing should be related to the magnitude of a cost
      effectiveness ratio. A common view that cost sharing should vary inversely with
      program cost-effectiveness is shown to be incorrect. A key issue in correct
      analysis is whether there is heterogeneity in marginal effectiveness of care that
      cannot be perceived by the social planner but is known by the demander. It is
      possible that some programs that would fail the social efficiency test at full
      coverage will be acceptable with positive cost sharing. Combining individual and
      social preferences affects both the choice of programs and the extent of cost
      sharing.

PMID- 24677290
TI  - Rapid coating of surfaces with functionalized nanoparticles for regulation of
      cell behavior.
AB  - A robust monolayer of nanoparticles is formed via dip-coating of cell culture
      plates. These surfaces provide cell type-specific modulation of growth behavior
      without the uptake of nanoparticles. 

PMID- 24677291
TI  - Retinoic acid induces mouse bone marrow-derived CD15+, Oct4+ and CXCR4+ stem
      cells into male germ-like cells in a two-dimensional cell culture system.
AB  - We have examined the effect of retinoic acid (RA) on differentiation of bone
      marrow-derived CD15(+) , Oct4(+) and CXCR4(+) cells into male germ cells. Bone
      marrow stem cells (BMSCs) were isolated from the femur of 3-4-week-old male
      C57BL/6 mice. Magnetic-activated cell sorting (MACS) system was used to sort
      CD15(+) , Oct4(+) and CXCR4(+) cells. RT-PCR was used to follow the expression of
      pluripotency markers. Sorted CD15(+) , Oct4(+) and CXCR4(+) cells were cultured
      in an undifferentiated condition on a feeder layer of mitomycin C-inactivated
      C2C12. The embryoid-like bodies were differentiated into male germ cells by
      retinoic acid. To identify the expression of male germ specific markers,
      differentiated cells were analysed by means of reverse transcriptase polymerase
      chain reaction (RT-PCR) and immunofluorescence staining. RT-PCR and
      immunofluorescence show that bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+)
      cells express pluripotency markers, Oct4, Nanog, Rex-1, SOX-2 and AP. The
      purified CD15(+) , Oct4(+) and CXCR4(+) formed structures like embryoid bodies
      when plated over a feeder layer; these bodies were alkaline phosphatase positive.
      When cells were induced by RA, bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+)
      were positive for Mvh, Dazl, Piwil2, Dppa3 and Stra8, that known molecular
      markers of male germ cells. Thus RA can induce differentiation of mouse bone
      marrow-derived CD15(+) , Oct4(+) and CXCR4(+) cells into male germ cells in
      vitro. Negative results for the gene expression analysis of female germ cells
      markers, GDF9 and ZP3, confirmed this conclusion. 

PMID- 24677292
TI  - Fetoscopic laser coagulation for twin-twin transfusion syndrome before 17 weeks'
      gestation: laser data, complications and neonatal outcome.
AB  - OBJECTIVE: To compare laser data, complications and neonatal outcome in
      pregnancies that undergo 'early' (<= 17 weeks' gestation) fetoscopic laser
      ablation of placental vascular anastomoses for twin-twin transfusion syndrome
      (TTTS) with those from 'conventional' cases treated after 17 weeks. METHODS: This
      was a cohort study of data collected prospectively between January 2004 and
      December 2012. We included monochorionic diamniotic twin pregnancies complicated
      by TTTS and treated by fetoscopic laser coagulation. Pregnancies were grouped
      according to laser treatment <= 17 gestational weeks or > 17 weeks and obstetric
      and neonatal outcomes were compared between groups. RESULTS: A total of 178
      pregnancies with TTTS underwent laser therapy: 40 at or before 17 weeks and 138
      after 17 weeks. There was no statistically significant difference between these
      two groups with respect to the rate of preterm prelabor rupture of membranes
      (PPROM), gestational age at PPROM and rate of PPROM occurring in the 7 days
      following fetoscopic laser coagulation. In the early group, the interval between
      performing fetoscopic laser coagulation and the time of delivery was
      significantly longer (104 days vs 74 days, P=0.0002) and the delivery rate within
      7 days of laser treatment was significantly lower (2.5% vs 15.9%, P=0.026). There
      was no significant difference between the two groups with regard to the rates of
      pregnancy without live birth (15.4% vs 15.4%, P=0.993), with one live birth
      (84.6% vs 84.6%, P=0.993) and with two live births (64.1% vs 58.1%, P=0.500).
      CONCLUSION: In the event of early TTTS, fetoscopic laser coagulation is
      technically feasible before 17 gestational weeks and obstetric and neonatal
      outcomes are comparable with those in cases of laser treatment performed after 17
      weeks.

PMID- 24677293
TI  - Reduction in proximal femoral strength in patients with acute spinal cord injury.
AB  - Bone loss after spinal cord injury (SCI) is associated with an increased risk of
      fracture resulting from minor trauma. Proximal femoral fractures account for
      approximately 10% to 20% of the fractures in this population and are among the
      most serious of injuries. Our purpose was to quantify changes to proximal femoral
      strength in patients with acute SCI. Thirteen subjects received dual-energy X-ray
      absorptiometry (DXA) and clinical computed tomography (CT) scans at serial time
      points during acute SCI separated by a mean of 3.5 months (range 2.6 to 4.8
      months). Areal bone mineral density (aBMD) at the proximal femur was quantified
      from DXA, and proximal femoral strength was predicted using CT-based finite
      element (FE) modeling in a sideways fall configuration. During the acute period
      of SCI, femoral neck and total proximal femur aBMD decreased by 2.0 +/-
      1.1%/month (p < 0.001) and 2.2 +/- 0.7%/month (p < 0.001), respectively. The
      observed reductions in aBMD were associated with a 6.9 +/- 2.0%/month (p < 0.001)
      reduction in femoral strength. Thus, changes in femoral strength were some 3
      times greater than the observed changes in aBMD (p < 0.001). It was interesting
      to note that in just 3.5 months of acute SCI, reductions in strength for some
      patients were on the order of that predicted for lifetime declines owing to
      aging. Therefore, it is important that therapeutic interventions are implemented
      soon after SCI in an effort to halt bone loss and decrease fracture risk. In
      addition, clinicians utilizing DXA to monitor bone health after SCI should be
      aware of the potential discrepancy between changes in aBMD and strength.

PMID- 24677294
TI  - Activity budget, diet, and habitat use in the critically endangered Ka'apor
      capuchin monkey (Cebus kaapori) in Para State, Brazil: a preliminary comparison
      to other capuchin monkeys.
AB  - The Ka'apor capuchin, Cebus kaapori, is perhaps the most endangered primate of
      the Brazilian Amazon. Endemic to a region with extreme intensification of habitat
      degrading activities, it survives in remnant populations in a completely
      fragmented landscape. Before now, the only data available were isolated
      observations of feeding, locality records, and information on population
      densities and group size obtained during census. Here we present the first data
      on the activity budget, diet, and daily path length of the species, and compare
      our preliminary results with those for other capuchin monkeys. A group of nine
      Ka'apor capuchins was monitored over a period of four months during the dry
      season in the Goianesia do Para municipality, Para, Brazil. We used instantaneous
      scan sampling (n = 4,647 scans) to construct an activity budget for the monkeys,
      and we identified the plants in their diet to species level (n = 41 plant taxa),
      allowing us to compare dietary overlap with other gracile capuchin species, as
      well as with the robust capuchin (Sapajus spp.), a potential competitor present
      throughout the range of the Ka'apor capuchin. Like other species of gracile
      capuchins, C. kaapori was highly frugivorous, with the vast majority of the
      feeding records of arils and fruit pulp (74%), supplemented by arthropods (13%)
      and seeds (10%), although diet composition was highly variable across months. The
      group used a total area of 62.4 ha during the study period, and average daily
      path length was 2,173 m (+/-400 m), with the entire home range utilized in every
      month of the study. We found significant overlap in the diet of the Ka'apor
      capuchin and Sapajus, highlighting the urgency to increase knowledge of the
      ecological needs of C. kaapori and understand synergistic effects of sympatry
      with competitive species, increasing forest fragmentation, and widespread human
      impact on C. kaapori sustainability.

PMID- 24677296
TI  - Improved frequency selective fat suppression in the posterior neck with tissue
      susceptibility matched pyrolytic graphite foam.
AB  - PURPOSE: To demonstrate improved frequency selective fat suppression in MRI using
      a magnetic susceptibility matching foam by reducing B0 inhomogeneities induced
      within the body by air-tissue interfaces. MATERIALS AND METHODS: Flexible
      pyrolytic graphite (PG) composite foam was tailored to match the magnetic
      susceptibility of human tissue and was shaped to surround the cervical spine
      region. Field maps and frequency selective fat suppressed T1 -weighted FLASH
      images were acquired at 3 Tesla in both phantoms and six healthy necks. RESULTS:
      B0 field uniformity was shimmed to a target critical threshold of 1 ppm for fat
      suppression. The percentage of voxels in the phantom that did not achieve the
      critical threshold was reduced from 64% without the PG foam to only 1% with the
      foam. A similar decrease from 16% to 2% was observed in the in vivo region of
      interest. CONCLUSION: PG foam improved B0 field uniformity by moving air-tissue
      field gradients outside of the neck where they cannot cause MRI artifacts. The PG
      foams consistently mitigated signal dropout, improved overall SNR, and enabled
      more robust frequency selective fat suppression.

PMID- 24677295
TI  - Anterior-posterior cerebral blood volume gradient in human subiculum.
AB  - The human hippocampal formation is characterized by anterior-posterior gradients
      of cell density, neurochemistry, and hemodynamics. In addition, some functions
      are associated with specific subfields (subiculum, CA1-4, dentate gyrus) and
      regions (anterior and posterior). We performed contrast-enhanced, high-resolution
      T1-weighted 3T steady state (SS) imaging to investigate cerebral blood volume
      (CBV) gradients of the hippocampal formation. We studied 14 healthy subjects and
      found significant CBV gradients (anterior > posterior) in the subiculum but not
      in other hippocampal subfields. Since CBV is a marker of basal metabolism, these
      results indicate a greater baseline activity in the anterior compared with the
      posterior subiculum. This gradient might be related to the role of the subiculum
      as the main outflow station of the hippocampal formation and might have
      implications for the mechanisms of neuropsychiatric disorders.

PMID- 24677297
TI  - Electro-induced mechanical and thermal responses of carbon nanotube fibers.
AB  - The electromechanical and electrothermal responses of carbon nanotube fibers
      provide new ways to use energy conversion, including the modulation of assembly
      structures by alternative densification and relaxation. The most efficient way to
      strengthen the tensile strength up to 2.32-2.50 GPa is shown as well as a
      microscale, nanotube-based Chinese calligraphy brush. 

PMID- 24677298
TI  - Molecular polymorphism of the ABO blood group: a study in Poland, Spain, and
      Andorra.
AB  - OBJECTIVES: The main goal of this study is to increase knowledge on the molecular
      level of the ABO blood group system in Europe by providing data for Poland,
      Spain, and Andorra populations. METHODS: A total of 172 oral scrapings samples
      from individuals of Polish origin, 108 peripheral blood samples of autochthonous
      individuals from the province of Zamora (Spain), and 81 peripheral blood samples
      from individuals with Andorran origin, were analyzed. Molecular characterization
      of the allelic variants was performed by the analysis of exons 6 and 7 of the ABO
      gene. RESULTS: Seven common alleles were identified, namely: A101, A102, A201,
      B101, O01, O02, and O03. Less common variants (O05, O09, O21, O26, O06, O11, and
      O12), were also detected. CONCLUSIONS: The results obtained contribute to the
      knowledge of the molecular European ABO map, and are discussed in regard to the
      allelic frequency reported by other Caucasian and Asian populations.

PMID- 24677299
TI  - Liquid chromatographic resolution of mexiletine and its analogs on crown ether
      based chiral stationary phases.
AB  - Mexiletine, an effective class IB antiarrhythmic agent, and its analogs were
      resolved on three different crown ether-based chiral stationary phases (CSPs),
      one (CSP 1) of which is based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid
      and the other two (CSP 2 and CSP 3) are based on (3,3'-diphenyl-1,1'-binaphthyl)
      20-crown-6. Mexiletine was resolved with a resolution (R(S)) of greater than 1.00
      on CSP 1 and CSP 3 containing residual silanol group-protecting n-octyl groups on
      the silica surface, but with a resolution (R(S)) of less than 1.00 on CSP 2. The
      chromatographic behaviors for the resolution of mexiletine analogs containing a
      substituted phenyl group at the chiral center on the three CSPs were quite
      dependent on the phenoxy group of analytes. Namely, mexiletine analogs containing
      2,6-dimethylphenoxy, 3,4-dimethylphenoxy, 3-methylphenoxy, 4-methylphenoxy, and a
      simple phenoxy group were resolved very well on the three CSPs even though the
      chiral recognition efficiencies vary with the CSPs. However, mexiletine analogs
      containing 2-methylphenoxy group were not resolved at all or only slightly
      resolved. Among the three CSPs, CSP 3 was found to show the highest chiral
      recognition efficiencies for the resolution of mexiletine and its analogs,
      especially in terms of resolution (R(S)).

PMID- 24677300
TI  - Pilot study: Raman spectroscopy in differentiating premalignant and malignant
      oral lesions from normal mucosa and benign lesions in humans.
AB  - BACKGROUND: Current practice for differentiating tissue lesions are based on
      histopathological criteria. This process is subject to error. The purpose of this
      study was to test whether an alternative, tissue-based molecular signatures Raman
      spectra could be used to differentiate premalignant and malignant lesions from
      normal mucosa or benign lesions. METHODS: Eighteen treatment naive subjects with
      histologically diagnosed oral disease were studied by comparing the Raman spectra
      of lesions with contralateral healthy sites. Principle component and multivariate
      analysis were used to predict which of the tissue groups the average spectrum of
      each lesion or normal tissue belonged. RESULTS: The average spectra were clearly
      different between premalignant and malignant lesions and those derived from
      normal, benign tissues. Premalignant and malignant lesions could be predicted
      with 100% sensitivity and 77% specificity. CONCLUSION: Raman spectroscopy (RS)
      offers the potential to provide point of care diagnosis of oral disease using a
      noninvasive, convenient, and relatively inexpensive technology.

PMID- 24677301
TI  - A microporous anionic metal-organic framework for sensing luminescence of
      lanthanide(III) ions and selective absorption of dyes by ionic exchange.
AB  - Herein, a novel anionic framework with primitive centered cubic (pcu) topology,
      [(CH3 )2 NH2 ]4 [(Zn4 dttz6 )Zn3 ]?15 DMF?4.5 H2 O, (IFMC-2; H3 dttz=4,5-di(1H
      tetrazol-5-yl)-2H-1,2,3-triazole) was solvothermally isolated. A new example of a
      tetranuclear zinc cluster {Zn4 dttz6 } served as a secondary building unit in
      IFMC-2. Furthermore, the metal cluster was connected by Zn(II) ions to give rise
      to a 3D open microporous structure. The lanthanide(III)-loaded metal-organic
      framework (MOF) materials Ln(3+) @IFMC-2, were successfully prepared by using ion
      exchange experiments owing to the anionic framework of IFMC-2. Moreover, the
      emission spectra of the as-prepared Ln(3+) @IFMC-2 were investigated, and the
      results suggested that IFMC-2 could be utilized as a potential luminescent probe
      toward different Ln(3+) ions. Additionally, the absorption ability of IFMC-2
      toward ionic dyes was also performed. Cationic dyes can be absorbed, but not
      neutral and anionic dyes, thus indicating that IFMC-2 exhibits selective
      absorption toward cationic dyes. Furthermore, the cationic dyes can be gradually
      released in the presence of NaCl. 

PMID- 24677302
TI  - Regio- and enantioselective synthesis of N-allylindoles by iridium-catalyzed
      allylic amination/transition-metal-catalyzed cyclization reactions.
AB  - Regio- and enantioselective synthesis of N-allylindoles was realized through an
      iridium-catalyzed asymmetric allylic amination reaction with 2-alkynylanilines
      and subsequent transition-metal-catalyzed cyclization reactions. The highly
      enantioenriched allylic amines prepared from Ir-catalysis were treated with
      catalytic amount of NaAuCl4?2 H2O or PdCl2 providing various substituted N
      allylindoles in excellent yields and enantioselectivities.

PMID- 24677303
TI  - Bioavailability and bioaccumulation of sediment-bound polychlorinated biphenyls
      to carp.
AB  - The relative bioavailability of sediment-bound polychlorinated biphenyls (PCBs
      138, 153, and 180) from a local contaminated site was examined using an in vivo
      carp model. Surface sediment from the PCB-contaminated site and spiked canola oil
      containing equivalent masses of PCBs were respectively incorporated in the
      sediment-dosed diets and oil-dosed diets at 3 dose levels resulting in 6
      experimental diets. Juvenile carps (n = 90) were divided in 18 tanks (5 fish * 6
      treatments * 3 tanks). Fish were fed the control diet during the adaptation
      period (15 d). Next, 1 fish was sampled in each tank and muscle tissues were
      combined in control groups. During the exposure period (15 d), the remaining fish
      were fed with 1 of the 6 experimental diets. At the end of the experiment, fish
      were sampled and muscle tissues were combined for each tank. The PCBs were
      monitored in feed and fish muscle. For both the contaminated sediment and spiked
      canola oil groups, concentrations of PCBs 138, 153, and 180 in muscle linearly
      increased with concentrations in food, with similar intercepts and slopes. In the
      present study, the sediment-bound PCBs were as bioavailable as those spiked into
      canola oil and fed to carp in a standard diet.

PMID- 24677304
TI  - A comprehensive library-based, automated screening procedure for 46 synthetic
      cannabinoids in serum employing liquid chromatography-quadrupole ion trap mass
      spectrometry with high-temperature electrospray ionization.
AB  - Considering the vast variety of synthetic cannabinoids and herbal mixtures -
      commonly known as 'Spice' or 'K2' - on the market and the resulting increase of
      severe intoxications related to their consumption, there is a need in clinical
      and forensic toxicology for comprehensive up-to-date screening methods. The focus
      of this project aimed at developing and implementing an automated screening
      procedure for the detection of synthetic cannabinoids in serum using a liquid
      chromatography-ion trap-MS (LC-MS(n)) system and a spectra library-based
      approach, currently including 46 synthetic cannabinoids and 8 isotope labelled
      analogues. In the process of method development, a high-temperature ESI source
      (IonBooster(TM), Bruker Daltonik) and its effects on the ionization efficiency of
      the investigated synthetic cannabinoids were evaluated and compared to a
      conventional ESI source. Despite their structural diversity, all investigated
      synthetic cannabinoids benefitted from high-temperature ionization by showing
      remarkably higher MS intensities compared to conventional ESI. The employed
      search algorithm matches retention time, MS and MS(2)/MS(3) spectra. With the
      utilization of the ionBooster source, limits for the automated detection
      comparable to cut-off values of routine MRM methods were achieved for the
      majority of analytes. Even compounds not identified when using a conventional ESI
      source were detected using the ionBooster-source. LODs in serum range from 0.1
      ng/ml to 0.5 ng/ml. The use of parent compounds as analytical targets offers the
      possibility of instantly adding new emerging compounds to the library and
      immediately applying the updated method to serum samples, allowing the rapid
      adaptation of the screening method to ongoing forensic or clinical requirements.
      The presented approach can also be applied to other specimens, such as oral fluid
      or hair, and herbal mixtures and was successfully applied to authentic serum
      samples. Quantitative MRM results of samples with analyte concentrations above
      the determined LOD were confirmed as positive findings by the presented method.

PMID- 24677305
TI  - Simultaneous detection of stable isotope-labeled and unlabeled L-tryptophan and
      of its main metabolites, L-kynurenine, serotonin and quinolinic acid, by gas
      chromatography/negative ion chemical ionization mass spectrometry.
AB  - A method for the detection of unlabeled and (15)N2 -labeled L-tryptophan (L-Trp),
      L-kynurenine (L-Kyn), serotonin (5-HT) and quinolinic acid (QA) in human and rat
      plasma by GC/MS is described. Labeled and unlabeled versions of these four
      products were analyzed as their acyl substitution derivatives using
      pentafluoropropionic anhydride and 2,2,3,3,3-pentafluoro-1-propanol. Products
      were then separated by GC and analyzed by selected ion monitoring using negative
      ion chemical ionization mass spectrometry. L-[(13)C11, (15)N2]-Trp, methyl
      serotonin and 3,5-pyridinedicarboxylic acid were used as internal standards for
      this method. The coefficients of variation for inter-assay repeatability were
      found to be approximately 5.2% for L-Trp and (15)N2-Trp, 17.1% for L-Kyn, 16.9%
      for 5-HT and 5.8% for QA (n = 2). We used this method to determine isotope
      enrichments in plasma L-Trp over the course of a continuous, intravenous infusion
      of L-[(15) N2 ]Trp in pregnant rat in the fasting state. Plasma (15)N2-Trp
      enrichment reached a plateau at 120 min. The free Trp appearance rate (Ra) into
      plasma was 49.5 +/- 3.35 umol/kg/h. The GC/MS method was applied to determine the
      enrichment of (15)N-labeled L-Trp, L-Kyn, 5-HT and QA concurrently with the
      concentration of non-labeled L-Trp, L-Kyn, 5-HT and QA in plasma. This method may
      help improve our understanding on L-Trp metabolism in vivo in animals and humans
      and potentially reveal the relative contribution of the four pathways of L-Trp
      metabolism.

PMID- 24677306
TI  - Matrix-free single-cell LDI-MS investigations of the diatoms Coscinodiscus granii
      and Thalassiosira pseudonana.
AB  - Single-cell investigations of the diatoms Coscinodsicus granii and Thalassiosira
      pseudonana were performed using laser desorption/ionization (LDI)-MS without the
      addition of chemical matrices. The unique cell wall architecture of these
      microalgae, more precisely the biomineralized nanostructured surface, supported
      the ionization of cellular as well as surface-related metabolites. In model
      experiments with purified diatom cell walls of eight species C. granii and T.
      pseudonana proved to promote the ionization of the polymer polyethylene glycol
      most efficiently. These species were therefore chosen for further experiments.
      Without any additional workup, living diatom cells can be washed, can be placed
      on the LDI target and can immediately be profiled using LDI-MS. Characteristic
      signals arising from the two species were assigned to common metabolites known
      from diatom metabolism. Among others, chlorophyll, phospholipids and amino acids
      were detected. Using these fingerprint signals, we were able to perform species
      specific MS imaging down to a single-cell resolution of 20 by 20 um. The larger
      C. granii cells can be directly visualized, while more than one of the smaller T.
      pseudonana cells is needed to generate high-quality images. The introduced
      technique will pave the way toward a chemotyping of phytoplankton that will
      enable the automated annotation of microalgal species. But also, an assignment of
      metabolic plasticity on a single-cell level that could answer fundamental
      questions about plankton diversity is now in reach.

PMID- 24677307
TI  - Characterization of multiple fragmentation pathways initiated by collision
      induced dissociation of multifunctional anions formed by deprotonation of 2
      nitrobenzenesulfonylglycine.
AB  - The correlation of anion structure with the fragmentation behavior of
      deprotonated nitrobenzenesulfonylamino acids was investigated using tandem mass
      spectrometry, isotopic labeling and computational methods. Four distinct
      fragmentation pathways resulting from the collision-induced dissociation (CID) of
      deprotonated 2-nitrobenzenesulfonylglycine (NsGly) were characterized. The
      unusual loss of the aryl nitro substituent as HONO was the lowest energy process.
      Subsequent successive losses of CO, HCN and SO2 indicated that an ortho
      cyclization reaction had accompanied loss of HONO. Other pathways involving
      rearrangement of the ionized sulfonamide group, dual bond cleavage and
      intramolecular nucleophilic displacement were proposed to account for the
      formation of phenoxide, arylsulfinate and arylsulfonamide product ions at higher
      collision energies. The four distinct fragmentation pathways were consistent with
      precursor-product relationships established by CID experiments, isotopic labeling
      results and the formation of analogous product ions from 2,4
      dinitrobenzenesulfonylglycine and the Ns derivatives of alanine and 2
      aminoisobutyric acid. The computations confirmed a low barrier for ortho
      cyclization with loss of HONO and feasible energetics for each reaction step in
      the four pathways. Computations also indicated that three of the fragmentation
      pathways started from NsGly ionized at the carboxyl group. Overall, the pathways
      identified for the fragmentation of the NsGly anion differed from processes
      reported for anions containing a single functional group, demonstrating the
      importance of functional group interactions in the fragmentation pathways of
      multifunctional anions.

PMID- 24677311
TI  - Characterization of supramolecular hidden chirality of hydrogen-bonded networks
      by advanced graph set analysis.
AB  - Supramolecular hidden chirality of hydrogen-bonded (HB) networks of primary
      ammonium carboxylates was exposed by advanced graph set analysis from a symmetric
      viewpoint in topology. The ring-type HB (R-HB) networks are topologically
      regarded as faces, and therefore exhibit prochirality and positional isomerism
      due to substituents attached on the faces. To describe the symmetric properties
      of the faces, additional symbols, Re (right-handed or clockwise), Si (left-handed
      or anticlockwise), and m (mirror), were proposed. According to the symbols,
      various kinds of faces were classified based on the symmetry. This symmetry
      consideration of the faces enables us to precisely evaluate supramolecular
      chirality, especially its handedness, of 0D-cubic, 1D-ladder and 2D-sheet HB
      networks that are composed of the faces. The 1D-ladder and 2D-sheet HB networks
      generate chirality by accumulating the chiral faces in 1D and 2D manners,
      respectively, whereas 0D-cubic HB networks generate chirality based on
      combinations of eight kinds of faces, similar to the chirality of dice.

PMID- 24677308
TI  - Glutathionylated gammaG and gammaA subunits of hemoglobin F: a novel post
      translational modification found in extremely premature infants by LC-MS and
      nanoLC-MS/MS.
AB  - Oxidative stress plays an important role in the development of various disease
      processes and is a putative mechanism in the development of bronchopulmonary
      dysplasia, the most common complication of extreme preterm birth. Glutathione, a
      major endogenous antioxidant and redox buffer, also mediates cellular functions
      through protein thiolation. We sought to determine if post-translational thiol
      modification of hemoglobin F occurs in neonates by examining erythrocyte samples
      obtained during the first month of life from premature infants, born at 23 0/7 -
      28 6/7 weeks gestational age, who were enrolled at our center in the Prematurity
      and Respiratory Outcomes Program (PROP). Using liquid chromatography-mass
      spectrometry (LC-MS), we report the novel finding of in vivo and in vitro
      glutathionylation of gammaG and gammaA subunits of Hgb F. Through tandem mass
      spectrometry (nanoLC-MS/MS), we confirmed the adduction site as the Cys-gamma94
      residue and through high-resolution mass spectrometry determined that the
      modification occurs in both gamma subunits. We also identified glutathionylation
      of the beta subunit of Hgb A in our patient samples; we did not find modified
      alpha subunits of Hgb A or F. In conclusion, we are the first to report that
      glutathionylation of gammaG and gammaA of Hgb F occurs in premature infants.
      Additional studies of this post-translational modification are needed to
      determine its physiologic impact on Hgb F function and if sG-Hgb is a biomarker
      for clinical morbidities associated with oxidative stress in premature infants.

PMID- 24677312
TI  - Growth of large-area 2D MoS2(1-x) Se2x semiconductor alloys.
AB  - Semiconducting MoS2(1-x) Se2x mono-layers where x = 0-0.40 are successfully grown
      over large areas. A random arrangement of the S and Se atoms and a tunable
      bandgap photoluminescence are observed. Atomically thin, 2D semiconductor alloys
      with tunable bandgaps have potential applications in nano- and opto-electronics.
      Field-effect transistors fabricated with the monolayers exhibit high on/off
      ratios of >10(5).

PMID- 24677313
TI  - Cell-permeant and photocleavable chemical inducer of dimerization.
AB  - Chemical inducers of dimerization (CIDs) have been developed to orchestrate
      protein dimerization and translocation. Here we present a novel photocleavable
      HaloTag- and SNAP-tag-reactive CID (MeNV-HaXS) with excellent selectivity and
      intracellular reactivity. Excitation at 360 nm cleaves the methyl-6-nitroveratryl
      core of MeNV-HaXS. MeNV-HaXS covalently links HaloTag- and SNAP-tag fusion
      proteins, and enables targeting of selected membranes and intracellular
      organelles. MeNV-HaXS-mediated translocation has been validated for plasma
      membrane, late endosomes, lysosomes, Golgi, mitochondria, and the actin
      cytoskeleton. Photocleavage of MeNV-HaXS liberates target proteins and provides
      access to optical manipulation of protein relocation with high spatiotemporal and
      subcellular precision. MeNV-HaXS supports kinetic studies of protein dynamics and
      the manipulation of subcellular enzyme activities, which is exemplified for Golgi
      targeted cargo and the assessment of nuclear import kinetics. 

PMID- 24677314
TI  - The effects of a soft drink tax in the UK.
AB  - The majority of the UK population is either overweight or obese. Health
      economists, nutritionists and doctors are calling for the UK to follow the
      example of other European countries and introduce a tax on soft drinks as a
      result of the perception that high intakes contribute to diet-related disease. We
      use a demand model estimated with household-level data on beverage purchases in
      the UK to investigate the effects of a tax on soft drink consumption. The model
      is a Quadratic Almost Ideal Demand System, and censoring is handled by applying a
      double hurdle. Separate models are estimated for low, moderate and high consumers
      to allow for a differential impact on consumption between these groups. Applying
      different hypothetical tax rates, we conclude that understanding the nature of
      substitute/complement relationships is crucial in designing an effective policy
      as these relationships differ between consumers depending on their consumption
      level. The overall impact of a soft drink tax on calorie consumption is likely to
      be small.

PMID- 24677315
TI  - ACC/AHA statement on cost/value methodology in clinical practice guidelines and
      performance measures: a report of the American College of Cardiology/American
      Heart Association Task Force on Performance Measures and Task Force on Practice
      Guidelines.

PMID- 24677316
TI  - The perivascular niche governs an autoregulatory network to support breast cancer
      metastasis.
AB  - Unravelling the autoregulatory network that induces and maintains cancer stem
      cell state may provide novel effective therapies against breast cancer
      metastasis. The perivascular niche develops elements that initiate the
      autoregulatory machine to induce and maintain cancer stem cells, but not EMT,
      among newly arrived tumour cells. Inhibition of one or more primary key elements
      that trigger this circuit may result in the prevention or cure of breast cancer
      metastasis. 

PMID- 24677318
TI  - ZnGa2O4 nanorod arrays decorated with Ag nanoparticles as surface-enhanced Raman
      scattering substrates for melamine detection.
AB  - The availability of sensitive, reproducible, and stable substrates is critically
      important for surface-enhanced Raman spectroscopy (SERS)-based applications, but
      it presently remains a challenge. In this work, well-aligned zinc gallate
      (ZnGa2O4) nanorod arrays grown on a Si substrate by chemical vapor deposition
      were used as templates to fabricate SERS substrates by deposition of Ag
      nanoparticles onto the ZnGa2O4 nanorod surfaces. The coverage of the Ag
      nanoparticles on the ZnGa2O4 nanorod surfaces was easily controlled by varying
      the amount of AgNO3. SERS measurements showed that the number density of Ag
      nanoparticles on the ZnGa2O4 nanorod surfaces had a great effect on SERS
      activity. The SERS signals collected by point-to-point and SERS mapping images
      showed that as-prepared SERS substrates exhibited good spatial uniformity and
      reproducibility. Detection of melamine molecules at low concentrations (1.0*10(
      7)  M) was used as an example to show the possible application of such a
      substrate. In addition, the effect of benzoic acid on the detection of melamine
      was also investigated. It was found that the SERS signal intensity of melamine
      decreased greatly as the concentration of benzoic acid was increased.

PMID- 24677317
TI  - Triazole-tailored guanosine dinucleosides as biomimetic ion channels to modulate
      transmembrane potential.
AB  - A "click" ion channel platform has been established by employing a clickable
      guanosine azide or alkyne with covalent spacers. The resulting guanosine
      derivatives modulated the traffic of ions across the phospholipid bilayer,
      exhibiting a variation in conductance spanning three orders of magnitude (pS to
      nS). Forster resonance energy transfer studies of the dansyl fluorophore with the
      membrane binding fluorophore Nile red revealed that the dansyl fluorophore is
      deeply embedded in the phospholipid bilayer. Complementary cytosine can inhibit
      the conductance of the supramolecular guanosine channels in the phospholipid
      bilayers.

PMID- 24677319
TI  - Butyrate modulates antioxidant enzyme expression in malignant and non-malignant
      human colon tissues.
AB  - The induction of antioxidant enzymes is an important mechanism in colon cancer
      chemoprevention, but the response of human colon tissue to butyrate, a gut
      fermentation product derived from dietary fiber, remains largely unknown.
      Therefore, our study investigated the effect of a butyrate treatment on catalase
      (CAT) and superoxide dismutase (SOD2) in matched human colon tissues of different
      transformation stages (n = 3-15 in each group) ex vivo. By performing
      quantitative real-time PCR, Western blot, and spectrophotometric measurements, we
      found an increase in SOD2 at expression and activity level in colonic
      adenocarcinomas (mRNA: 1.96-fold; protein: 1.41-fold, activity: 1.8-fold; P <
      0.05). No difference was detectable for CAT between normal, adenoma, and
      carcinoma colon tissues. Treatment of normal colon epithelium (12 h) with a
      physiologically relevant concentration of butyrate (10 mM) resulted in a
      significant increase (P < 0.05) in CAT mRNA (1.24-fold) and protein (1.39-fold),
      without affecting the enzymatic activity. Consequently, preliminary experiments
      failed to show any protective effect of butyrate against H2 O2 -mediated DNA
      damage. Despite a significantly lowered SOD2 transcript (0.51-fold, P < 0.01)
      and, to a lesser extent, protein level (0.86-fold) after butyrate exposure of
      normal colon cells, the catalytic activity was significantly enhanced (1.19-fold,
      P < 0.05), suggesting an increased protection against tissue superoxide radicals.
      In malignant tissues, greater variations in response to butyrate were observed.
      Furthermore, both enzymes showed an age-dependent decrease in activity in normal
      colon epithelium (CAT: r = -0.49, P = 0.09; SOD2: r = -0.58, P = 0.049). In
      conclusion, butyrate exhibited potential antioxidant features ex vivo but
      cellular consequences need to be investigated more in depth.

PMID- 24677320
TI  - Macromolecular uptake of alkyl-chain-modified guanidinoglycoside molecular
      transporters.
AB  - Guanidinoglycosides, a family of cellular transporters capable of delivering high
      Mw biopolymers, have previously been shown to display high selectivity for cell
      surface heparan sulfate proteoglycans and promote their clustering. Herein, the
      internalization mechanism of amphiphilic guanidinoglycoside derivatives was
      investigated by cell-surface FRET analysis. Unexpectedly, although the heparan
      sulfate selectivity is maintained, the cellular uptake of these derivatives does
      not appear to involve clustering of the proteoglycans on the cell surface. This
      suggests a distinct uptake mechanism when compared to the parent
      guanidinoglycoside-based carriers.

PMID- 24677321
TI  - Enhanced research assessment performance in graduate vs. undergraduate-entry
      medical students: implications for recruitment into academic medicine.
AB  - BACKGROUND: Studies investigating variance between the academic performance of
      direct-entry (DEM) versus graduate-entry (GEM) medical students have yielded
      conflicting results, but their performance in undergraduate research-based
      assessments has not been compared to-date. AIM: We aimed to compare the results
      of DEM and GEM students with respect to their senior research dissertation
      module. METHODS: This retrospective study examined the final year results between
      2011-2012 in DEM, (n = 219) and GEM (n = 84) students. Between-group comparisons
      of dissertation module marks were conducted using independent t-tests.
      Correlations between marks in dissertation module and in other disciplines
      assessed during the final year were attained using Pearson's correlation.
      Multiple regression analysis was employed to adjust for potential confounding
      factors such as student age and gender. RESULTS: No apparent difference was
      apparent between the DEM and GEM students with respect to results achieved across
      the clinical disciplines examined. However, GEM students performed significantly
      better than DEMs in their senior research dissertation assessment (Mean = 66.81%
      vs. 65.00%, fully adjusted p = 0.048). The variable which remained influential in
      regression analysis was nationality, where North American and Asian students were
      demonstrated to score lower than their Irish counterparts in the dissertation
      module (B coefficient = -1.90, SE = 0.94, P = 0.045 and B coefficient = -4.88, SE
      = 1.00, P < 0.001 respectively). CONCLUSIONS: Performance in the research-based
      module was significantly better in GEM relative to their DEM colleagues. This
      finding may have implications for future recruitment into academic medicine, as
      aptitude and interest in research at undergraduate level has been shown to be
      associated with increased likelihood of an academic career in medicine.

PMID- 24677322
TI  - Prospective comparison of 3T MRI with diffusion-weighted imaging and MDCT for the
      preoperative TNM staging of gastric cancer.
AB  - PURPOSE: To compare the diagnostic performance of 3T magnetic resonance imaging
      (MRI) with diffusion-weighted imaging (DWI) and multidetector-row computed
      tomography (MDCT) for the preoperative TNM staging of gastric cancer. MATERIALS
      AND METHODS: This prospective study was approved by our Institutional Review
      Board. Forty-nine consecutive patients with histologically confirmed gastric
      cancers underwent MDCT and 3T MRI followed by surgery. MRI without DWI, MRI with
      DWI, and MDCT were reviewed to determine preoperative TNM staging. Using the
      pathologic stages as the reference standard, the diagnostic performance of each
      imaging modality was compared. RESULTS: Diagnostic accuracies of MRI with DWI,
      MRI without DWI, and MDCT did not show a significant difference (<=T2 vs. >=T3:
      85.1%, 78.7%, and 80.9%; <=T3 vs. T4: 76.6%, 74.5%, and 72.3%; N-negative vs. N
      positive: 76.6%, 66.0%, and 63.8%; M0 vs. M1: all 95.9%, respectively) (P >
      0.05). For N staging, MRI with DWI demonstrated higher sensitivity but lower
      specificity (86.7% and 58.8%, respectively) than MRI without DWI (50.0% and
      94.1%) or MDCT (43.3% and 100%) (P < 0.05). CONCLUSION: The diagnostic accuracy
      of 3T MRI is comparable to that of MDCT for the preoperative TNM staging of
      gastric cancer, and for assessing LN metastasis, the addition of DWI to
      conventional MRI may increase the sensitivity.

PMID- 24677323
TI  - Charge-scaling effect in ionic liquids from the charge-density analysis of N,N'
      dimethylimidazolium methylsulfate.
AB  - The charge scaling effect in ionic liquids was explored on the basis of
      experimental and theoretical chargedensity analyses of [C1MIM][C1SO4] employing
      the quantum theory of atoms in molecules (QTAIM) approach. Integrated QTAIM
      charges of the experimental (calculated) charge density of the cation and anion
      resulted in non-integer values of +/-0.90 (+/-0.87) e. Efficient charge transfer
      along the bond paths of the hydrogen bonds between the imidazolium ring and the
      anion was considered as the origin of these reduced charges. In addition, a
      detailed QTAIM analysis of the bonding situation in the [C1SO4]- anion revealed
      the presence of negative piO->sigma*S-O hyperconjugation.

PMID- 24677324
TI  - Digit ratio (2D:4D) in Chinese women with breast cancer.
AB  - OBJECTIVES: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is
      established in utero and is positively correlated with oestrogen in men and
      women. It is a putative biomarker for prenatal hormone exposure and may represent
      an individual predisposition to certain diseases (e.g., breast cancer). The aim
      of the present study is to investigate whether there is a link between digit
      ratio (2D:4D) and breast cancer in Chinese populations. METHODS: The controls we
      chose were healthy subjects-age and -sex matched to the patients diagnosed with
      breast cancer. Photocopies of the two hands of 218 women (controls: 109;
      patients: 109) were collected. Left hand, right hand, mean hand, and right minus
      left 2D:4D (Dr-l ) were analyzed. RESULTS: The patients with breast cancer
      presented significantly higher 2D:4D than controls (left: P < 0.01; right: P <
      0.05; mean: P < 0.05). The mean values of 2D:4D on the left hand were
      significantly higher than those on the right hand in the two groups, respectively
      (controls: P < 0.05; patients: P <= 0.01). In patients, there was a significantly
      negative correlation between 2D:4D (left hand: P < 0.01; right hand, mean: P <
      0.05) and the presented age with breast cancer, but no association between Dr-l
      and age of presented disease. CONCLUSIONS: Digit ratio (2D:4D) may correlate with
      the increased risk of breast cancer.

PMID- 24677325
TI  - The first heteropentanuclear extended metal-atom chain: [Ni+-Ru25+-Ni2+-Ni2+
      (tripyridyldiamido)4(NCS)2].
AB  - This study develops the first heteropentametal extended metal atom chain (EMAC)
      in which a string of nickel cores is incorporated with a diruthenium unit to tune
      the molecular properties. Spectroscopic, crystallographic, and magnetic
      characterizations show the formation of a fully delocalized Ru2(5+) unit. This
      [Ru2]-containing EMAC exhibits single-molecule conductance four-fold superior to
      that of the pentanickel complex and results in features of negative differential
      resistance (NDR), which are unobserved in analogues of pentanickel and
      pentaruthenium EMACs. A plausible mechanism for the NDR behavior is proposed for
      this diruthenium-modulated EMAC.

PMID- 24677326
TI  - Enhanced immunoprotective effects by anti-IL-17 antibody translates to improved
      skeletal parameters under estrogen deficiency compared with anti-RANKL and anti
      TNF-alpha antibodies.
AB  - Activated T cell has a key role in the interaction between bone and immune
      system. T cells produce proinflammatory cytokines, including receptor activator
      of NF-kappaB ligand (RANKL), tumor necrosis factor alpha (TNF-alpha), and
      interleukin 17 (IL-17), all of which augment osteoclastogenesis. RANKL and TNF
      alpha are targeted by inhibitors such as denosumab, a human monoclonal RANKL
      antibody, and infliximab, which neutralizes TNF-alpha. IL-17 is also an important
      mediator of bone loss, and an antibody against IL-17 is undergoing phase II
      clinical trial for rheumatoid arthritis. Although there are a few studies showing
      suppression of Th17 cell differentiation and induction of regulatory T cells
      (Tregs) by infliximab, the effect of denosumab remains poorly understood. In this
      study, we investigated the effects of anti-TNF-alpha, anti-RANKL, or anti-IL-17
      antibody administration to estrogen-deficient mice on CD4(+) T-cell
      proliferation, CD28 loss, Th17/Treg balance and B lymphopoesis, and finally, the
      translation of these immunomodulatory effects on skeletal parameters. Adult
      Balb/c mice were treated with anti-RANKL/-TNF-alpha/-IL-17 subcutaneously, twice
      a week, postovariectomy (Ovx) for 4 weeks. Animals were then autopsied; bone
      marrow cells were collected for FACS and RNA analysis and serum collected for
      ELISA. Bones were dissected for static and dynamic histomorphometry studies. We
      observed that although anti-RANKL and anti-TNF-alpha therapies had no effect on
      Ovx-induced CD4(+) T-cell proliferation and B lymphopoesis, anti-IL-17
      effectively suppressed both events with concomitant reversal of CD28 loss. Anti
      IL-17 antibody reduced proinflammatory cytokine production and induced Tregs. All
      three antibodies restored trabecular microarchitecture with comparable efficacy;
      however, cortical bone parameters, bone biomechanical properties, and
      histomorphometry were best preserved by anti-IL-17 antibody, likely attributable
      to its inhibitory effect on osteoblast apoptosis and increased number of bone
      lining cells and Wnt10b expression. Based on the superior immunoprotective
      effects of anti-IL-17, which appears to translate to a better skeletal
      preservation, we propose beginning clinical trials using a humanized antibody
      against IL-17 for treatment of postmenopausal osteoporosis.

PMID- 24677327
TI  - Image-scoring system for crown-rump length measurement.
AB  - OBJECTIVE: To develop and evaluate an objective image-scoring system for crown
      rump length (CRL) measurements and to determine how this compares with subjective
      assessment. METHODS: A total of 125 CRL ultrasound images were selected from the
      database of the International Fetal and Newborn Growth Consortium for the 21(st)
      Century study group. Two reviewers, who were blinded to the operators' and to
      each others' results, evaluated all images both subjectively and objectively.
      Subjective evaluation consisted of rating an image as acceptable or unacceptable,
      while objective evaluation was based on six criteria. Reviewer differences for
      both the subjective and objective evaluations were compared using percentage of
      agreement and adjusted kappa values. RESULTS: The distribution of individual
      scores and differences between subjective and objective evaluation for the two
      reviewers was similar. Overall agreement between the reviewers was higher for
      objective evaluation (95.2%; adjusted kappa, 0.904), than for subjective
      evaluation (77.6%; adjusted kappa, 0.552). There was a high level of agreement
      for horizontal position (kappa = 0.951), magnification (kappa = 0.919),
      visualization of crown and rump (kappa = 0.806) and caliper placement (kappa =
      0.756), while agreement for mid-sagittal section (kappa = 0.629) and neutral
      position (kappa = 0.565) were moderate and poor, respectively. CONCLUSION: The
      proposed six-point scoring system for CRL image rating is more reproducible than
      is subjective evaluation and should be considered as a method of quality
      assessment and audit.

PMID- 24677328
TI  - Original electrospun core-shell nanostructured Magneli titanium oxide fibers and
      their electrical properties.
AB  - A combination of sol-gel chemistry and the electrospinning process leads to
      unprecedented versatility in the design of nano-Magneli phases. Adjusting
      experimental levers provides an efficient route for tuning the composition, the
      crystal structure, and the nano- and microstructure of titanium sub-oxides, thus
      paving the way to functional membranes and tissues. 

PMID- 24677329
TI  - Summary of proceedings of the second World Congress on Thyroid Cancer.
AB  - The second World Congress on Thyroid Cancer was held from July 10 to July 14,
      2013, in Toronto, Canada. Its purpose was to provide a platform for the
      multidisciplinary discussion on research, education, and patient management of
      thyroid malignancy. Herein, we summarize the latest major trends and
      controversies within the field of thyroid oncology as discussed in the Congress
      including the use of ultrasound, standardization of cytology, role of molecular
      testing, treatment options for small recurrence including ablation and
      observation, management of recurrent laryngeal nerve injury, importance of
      identification of the external branch of the superior laryngeal nerve, role of
      minimally invasive thyroid surgery, trends in radioactive iodine treatment,
      advancements in targeted agents, and the importance of personalizing treatment to
      individual patients.

PMID- 24677330
TI  - New synthetic routes towards soluble and dissymmetric triphenodioxazine dyes
      designed for dye-sensitized solar cells.
AB  - New pi-conjugated structures are constantly the subject of research in dyes and
      pigments industry and electronic organic field. In this context, the
      triphenodioxazine (TPDO) core has often been used as efficient photostable
      pigments and once integrated in air stable n-type organic field-effect transistor
      (OFET). However, little attention has been paid to the TPDO core as soluble
      materials for optoelectronic devices, possibly due to the harsh synthetic
      conditions and the insolubility of many compounds. To benefit from the
      photostability of TPDO in dye-sensitized solar cells (DSCs), an original
      synthetic pathway has been established to provide soluble and dissymmetric
      molecules applied to a suitable design for the sensitizers of DSC. The study has
      been pursued by the theoretical modeling of opto-electronic properties, the
      optical and electronic characterizations of dyes and elaboration of efficient
      devices. The discovery of new synthetic pathways opens the way to innovative
      designs of TPDO for materials used in organic electronics.

PMID- 24677331
TI  - An examination of the structural link between post-traumatic stress symptoms and
      chronic pain in the framework of fear-avoidance models.
AB  - BACKGROUND: The tendency to respond with fear and avoidance can be seen as a
      shared vulnerability contributing to the development of post-traumatic stress
      disorder (PTSD) and chronic pain. Although several studies have examined which
      specific symptoms of PTSD (re-experiencing, avoidance, emotional numbing and
      hyperarousal) are associated with chronic pain, none has considered this
      association within the framework of fear-avoidance models. METHODS: Seven hundred
      fourteen patients with chronic musculoskeletal pain were assessed. Of these, 149
      patients were selected for the study based upon the following inclusion criteria:
      exposure to a traumatic event before the onset of pain (with scores equal to or
      higher than 8 points on the fear and hopelessness scales of the Stressful Life
      Event Screening Questionnaire Revised) and scores equal to or higher than 30 on
      the Davidson Trauma Scale. RESULTS: Structural equation modelling was used to
      test the association between PTSD symptoms and pain outcomes (pain intensity and
      disability) using the mediating variables considered in the fear-avoidance
      models. The results show that emotional numbing and hyperarousal symptoms, but
      neither re-experiencing nor avoidance, affected pain outcome via anxiety
      sensitivity (AS), catastrophizing and fear of pain. PTSD symptoms increased the
      levels of AS, which predisposes to catastrophizing and, in turn, had an effect on
      the tendency of pain patients to respond with more fear and avoidance.
      CONCLUSIONS: This study provides empirical support for the potential role of PTSD
      symptoms in fear-avoidance models of chronic pain and suggests that AS is a
      relevant variable in the relationship between both disorders.

PMID- 24677332
TI  - Tunable plasmon resonances in two-dimensional molybdenum oxide nanoflakes.

PMID- 24677333
TI  - Polynuclear Sm(III) polyamidoamine-based dendrimer: a single probe for combined
      visible and near-infrared live-cell imaging.
AB  - We report herein the synthesis of a luminescent polynuclear dendritic structure
      (Sm(III)-G3P-2,3Nap) in which eight Sm(III) ions are sensitized by thirty-two 2,3
      naphthalimide chromophores. Upon a single excitation wavelength, the dendrimer
      complex exhibits two types of emission in the visible and in the near-infrared
      (NIR) ranges. Sm(III)-G3P-2,3Nap was non-cytotoxic after 24 h of incubation and
      up to 2.5 MUM. The ability of the Sm(III)-based probe to be taken up by cells was
      confirmed by confocal microscopy. Epifluorescence microscopy validated Sm(III)
      G3P-2,3Nap as a versatile probe, capable of performing interchangeably in the
      visible or NIR for live-cell imaging. As both emissions are obtained from a
      single complex, the cytotoxicity and biodistribution are inherently the same. The
      possibility for discriminating the sharp Sm(III) signals from autofluorescence in
      two spectral ranges increases the reliability of analysis and reduces the
      probability of artifacts and instrumental errors.

PMID- 24677334
TI  - Prevalence, intensity, and predictors of the supportive care needs of women
      diagnosed with breast cancer: a systematic review.
AB  - OBJECTIVE: The assessment of supportive care needs is a crucial step in the
      development of appropriate interventions that may improve the quality of life of
      cancer patients. This review describes and analyzes the prevalence and predictors
      of the unmet supportive care needs of breast cancer (BC) patients and survivors
      and suggests paths for further research. METHOD: Multiple databases were
      searched, considering only quantitative studies using validated needs assessment
      instruments and focusing uniquely on women diagnosed with BC. RESULTS: Out of 761
      hits, 23 studies answered to all eligibility criteria. Nineteen were cross
      sectional, and the remaining four were longitudinal. Most included patients at
      different moments along the BC trajectory, from diagnosis to decades into
      survivorship, with the major proportion of patients under treatment. Only five
      concentrated on the posttreatment phase into extended survivorship. The concerns
      of women diagnosed with BC clustered around psychological and information needs,
      with the top concern being 'fear of the cancer returning'. Predictors of higher
      levels of needs included advanced disease stage, greater symptom burden, shorter
      time since diagnosis, higher levels of distress, and younger age. Prevalence
      differed between cultures with Asian women reporting greater information needs
      and lower psychological needs compared with Western women. CONCLUSIONS: Revealing
      which needs BC patients consider most urgent and the factors related to greater
      needs will permit the development of improved and targeted supportive care.
      Future research should comprise longitudinal designs concentrating on women at
      specific moments along the BC trajectory for a dynamic understanding of these
      needs.

PMID- 24677335
TI  - Medical professionalism on television: student perceptions and pedagogical
      implications.
AB  - Previous research has pointed to the role television can play in informing health
      practices and beliefs. Within the academic setting in particular, some educators
      have raised concerns about the influence of medical dramas on students. Less
      research, however, draws on the perspectives of students, and this study
      therefore explores medical students' perceptions of medical practice and
      professionalism in popular medical television programmes. Qualitative data from
      surveys of Australian undergraduate medical students showed that students
      perceived professionalism in dichotomous ways, with three main themes: cure-care,
      where a doctor's skill is either technical or interpersonal; work-leisure, where
      a doctor is either dedicated to work or personal life; and clinical
      administration, where work is either direct patient care or administration. There
      continue to be imagined divisions between curing and caring for students, who
      express concerns about balancing work and leisure, and expectations that doctors
      should have little administrative work. Given students were able to identify
      these important contemporary issues around professionalism on television, there
      is pedagogical value in using popular images of the medical world in medical
      education. 

PMID- 24677336
TI  - International medical migration: a critical conceptual review of the global
      movements of doctors and nurses.
AB  - This paper critically appraises the discourse around international medical
      migration at the turn of the 21st century. A critical narrative review of a range
      of English-language sources, including grey literature, books and research
      reports, traces the development and spread of specific causative models. The
      attribution of causative relations between the movement of skilled medical
      workers, the provision of health care and population health outcomes illustrates
      how the global reach of biomedicine has to be understood in the context of local
      conditions. The need to understand migration as an aspect of uneven global
      development, rather than a delimited issue of manpower services management, is
      illustrated with reference to debates about 'brain drain' of Africa's health-care
      professionals, task-shifting and the crisis in health-care human resources. The
      widespread presumed cause of shortages of skilled health-care staff in sub
      Saharan Africa was overdetermined by a compelling narrative of rich countries
      stealing poor countries' trained health-care professionals. This narrative
      promotes medical professional interests and ignores historical patterns of
      underinvestment in health-care systems and structures. Sociological theories of
      medicalization suggest that the international marketization of medical
      recruitment is a key site where the uneven global development of capital is at
      work. A radical reconfiguration of medical staffing along the lines of 'task
      shifting' in rich and poor countries' health-care systems alike offers one means
      of thinking about global equity in access to quality care. 

PMID- 24677337
TI  - Parent-led conferences as sites of medical work.
AB  - Conferences are novel sites for understanding medical work. Through describing
      styles of presentation that take place at conferences attended by patients and
      parents, this article highlights how clinicians on stage present ordinary and
      extraordinary aspects of medicine. Attention is drawn to the reaction of the
      parents in the audience. The power of the presenter to direct proceedings
      highlights the potential vulnerability of the audience. The relationship between
      clinician on stage and parents in the audience reflects the clinical relationship
      between doctor and patient. But through identifying insiders and outsiders, the
      conference setting also enables new relationships and collective identities to be
      formed. Drawing on an ethnographic study of rare disease conferences, this
      article extends understanding of medical work by identifying how conferences
      offer new ways of witnessing the clinical gaze, the doctor-patient relationship
      and the formation and enactment of a conference community. 

PMID- 24677338
TI  - Prepubertal stress and hippocampal function: sex-specific effects.
AB  - The chances of developing psychiatric disorders in adulthood are increased when
      stress is experienced early in life. In particular, stress experienced in the
      childhood or 'prepubertal' phase is associated with the later development of
      disorders such as depression, anxiety, post-traumatic stress disorder, and
      psychosis. Relatively little is known about the biological basis of this effect,
      but one hypothesis is that prepubertal stress produces long-lasting changes in
      brain development, particularly in stress sensitive regions such as the
      hippocampus, leaving an individual vulnerable to disorders in adulthood. In this
      study, we used an animal model of prepubertal stress to investigate the
      hypothesis that prepubertal stress induces alterations in hippocampal function in
      adulthood. Male and female rats were exposed to a brief, variable prepubertal
      stress protocol (postnatal days 25-27), and their performance in two distinct
      hippocampal-dependent tasks (contextual fear and spatial navigation) was compared
      with controls in adulthood. Prepubertal stress significantly impaired contextual
      fear responses in males and enhanced performance in spatial navigation in
      females. These results demonstrate that exposure to a brief period of stress in
      the prepubertal phase alters hippocampal-dependent behaviors in adulthood in a
      sex-specific manner.

PMID- 24677339
TI  - Physiological advantages of C4 grasses in the field: a comparative experiment
      demonstrating the importance of drought.
AB  - Global climate change is expected to shift regional rainfall patterns,
      influencing species distributions where they depend on water availability.
      Comparative studies have demonstrated that C4 grasses inhabit drier habitats than
      C3 relatives, but that both C3 and C4 photosynthesis are susceptible to drought.
      However, C4 plants may show advantages in hydraulic performance in dry
      environments. We investigated the effects of seasonal variation in water
      availability on leaf physiology, using a common garden experiment in the Eastern
      Cape of South Africa to compare 12 locally occurring grass species from C4 and C3
      sister lineages. Photosynthesis was always higher in the C4 than C3 grasses
      across every month, but the difference was not statistically significant during
      the wettest months. Surprisingly, stomatal conductance was typically lower in the
      C3 than C4 grasses, with the peak monthly average for C3 species being similar to
      that of C4 leaves. In water-limited, rain-fed plots, the photosynthesis of C4
      leaves was between 2.0 and 7.4 MUmol m(-2) s(-1) higher, stomatal conductance
      almost double, and transpiration 60% higher than for C3 plants. Although C4
      average instantaneous water-use efficiencies were higher (2.4-8.1 mmol mol(-1))
      than C3 averages (0.7-6.8 mmol mol(-1)), differences were not as great as we
      expected and were statistically significant only as drought became established.
      Photosynthesis declined earlier during drought among C3 than C4 species,
      coincident with decreases in stomatal conductance and transpiration. Eventual
      decreases in photosynthesis among C4 plants were linked with declining midday
      leaf water potentials. However, during the same phase of drought, C3 species
      showed significant decreases in hydrodynamic gradients that suggested hydraulic
      failure. Thus, our results indicate that stomatal and hydraulic behaviour during
      drought enhances the differences in photosynthesis between C4 and C3 species. We
      suggest that these drought responses are important for understanding the
      advantages of C4 photosynthesis under field conditions.

PMID- 24677340
TI  - Development of selective inhibitors for human aldehyde dehydrogenase 3A1
      (ALDH3A1) for the enhancement of cyclophosphamide cytotoxicity.
AB  - Aldehyde dehydrogenase 3A1 (ALDH3A1) plays an important role in many cellular
      oxidative processes, including cancer chemoresistance, by metabolizing activated
      forms of oxazaphosphorine drugs such as cyclophosphamide (CP) and its analogues,
      such as mafosfamide (MF), ifosfamide (IFM), and 4-hydroperoxycyclophosphamide (4
      HPCP). Compounds that can selectively target ALDH3A1 could permit delineation of
      its roles in these processes and could restore chemosensitivity in cancer cells
      that express this isoenzyme. Here we report the detailed kinetic and structural
      characterization of an ALDH3A1-selective inhibitor, CB29, previously identified
      in a high-throughput screen. Kinetic and crystallographic studies demonstrate
      that CB29 binds within the aldehyde substrate-binding site of ALDH3A1. Cellular
      proliferation of ALDH3A1-expressing lung adenocarcinoma (A549) and glioblastoma
      (SF767) cell lines, as well as ALDH3A1 non-expressing lung fibroblast (CCD-13Lu)
      cells, is unaffected by treatment with CB29 and its analogues alone. However,
      sensitivity toward the anti-proliferative effects of mafosfamide is enhanced by
      treatment with CB29 and its analogue in the tumor cells. In contrast, the
      sensitivity of CCD-13Lu cells toward mafosfamide was unaffected by the addition
      of these same compounds. CB29 is chemically distinct from the previously reported
      small-molecule inhibitors of ALDH isoenzymes and does not inhibit ALDH1A1,
      ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 isoenzymes at concentrations up to 250 MUM.
      Thus, CB29 is a novel small molecule inhibitor of ALDH3A1, which might be useful
      as a chemical tool to delineate the role of ALDH3A1 in numerous metabolic
      pathways, including sensitizing ALDH3A1-positive cancer cells to
      oxazaphosphorines.

PMID- 24677342
TI  - Identification of novel transcription factors in osteoclast differentiation using
      genome-wide analysis of open chromatin determined by DNase-seq.
AB  - Clarification of the mechanisms underlying osteoclast differentiation enables us
      to understand the physiology of bone metabolism as well as the pathophysiology of
      bone diseases such as osteoporosis. Recently, it has been reported that
      epigenetics can determine cell fate and regulate cell type-specific gene
      expression. However, little is known about epigenetics during osteoclastogenesis.
      To reveal a part of epigenetics, especially focused on chromatin dynamics, during
      early osteoclastogenesis and to identify novel transcription factors involved in
      osteoclastogenesis, we performed a genome-wide analysis of open chromatin during
      receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis using
      DNase I hypersensitive sites sequencing (DNase-seq). DNase-seq was performed
      using the extracted nuclei from RAW264 cells treated with or without RANKL for 24
      hours, followed by several bioinformatic analyses. DNase I hypersensitive sites
      (DHSs) were dynamically changed during RANKL-induced osteoclastogenesis and they
      accumulated in promoter regions. The distributions of DHSs among cis-regulatory
      DNA regions were identical regardless of RANKL stimulation. Motif discovery
      analysis successfully identified well-known osteoclastogenic transcription
      factors including Jun, CREB1, FOS, ATF2, and ATF4, but also novel transcription
      factors for osteoclastogenesis such as Zscan10, Atf1, Nrf1, and Srebf2. siRNA
      knockdown of these identified novel transcription factors impaired
      osteoclastogenesis. Taken together, DNase-seq is a useful tool for comprehension
      of epigenetics, especially chromatin dynamics during osteoclastogenesis and for
      identification of novel transcription factors involved in osteoclastogenesis.
      This study may reveal underlying mechanisms that determine cell type-specific
      differentiation of bone cells and may lead to investigation of novel therapeutic
      targets for osteoporosis.

PMID- 24677343
TI  - Amphiphilic inclusion spaces for various guests and regulation of fluorescence
      intensity of 1,8-bis(4-aminophenyl)anthracene crystals.
AB  - A host framework for inclusion of various guest molecules was investigated by
      preparation of inclusion crystals of 1,8-bis(4-aminophenyl)anthracene (1,8-BAPA)
      with organic solvents. X-ray crystallographic analysis revealed construction of
      the same inclusion space incorporating 1,8-BAPA and eight guest molecules
      including both non-polar (benzene) and polar guests (N,N-dimethylformamide, DMF).
      Fluorescence efficiencies varied depending on guest molecule polarity; DMF
      inclusion crystals exhibited the highest fluorescence intensity (PhiF=0.40), four
      times as high as that of a benzene inclusion crystal (PhiF=0.10). According to
      systematic investigations of inclusion phenomena, strong host-guest interactions
      and filling of the inclusion space led to a high fluorescence intensity.
      Temperature-dependent fluorescence spectral measurements revealed these factors
      effectively immobilised the host framework. Although hydrogen bonding commonly
      decreases fluorescence intensity, the present study demonstrated that such strong
      interactions provide excellent conditions for fluorescence enhancement. Thus,
      this remarkable behaviour has potential application toward sensing of highly
      polar molecules, such as biogenic compounds.

PMID- 24677341
TI  - Nitric oxide donor NOC-5 increases XIAP and Aven level in Jurkat cells.
AB  - Mitochondrial permeabilisation after NO donor application did not activate
      caspase-9. We have studied the X-linked apoptosis inhibitor (XIAP) and Aven
      protein content in NO-treated Jurkat cells. The level of both proteins increased
      in NO-treated cells. Thus the increase in XIAP and Aven content could be the
      cause of the lack of caspase-9 activity after mitochondrial permeabilisation in
      NO-treated Jurkat cells. 

PMID- 24677344
TI  - Macroscopic control of helix orientation in films dried from cholesteric liquid
      crystalline cellulose nanocrystal suspensions.
AB  - The intrinsic ability of cellulose nanocrystals (CNCs) to self-organize into
      films and bulk materials with helical order in a cholesteric liquid crystal is
      scientifically intriguing and potentially important for the production of
      renewable multifunctional materials with attractive optical properties. A major
      obstacle, however, has been the lack of control of helix direction, which results
      in a defect-rich, mosaic-like domain structure. Herein, a method for guiding the
      helix during film formation is introduced, which yields dramatically improved
      uniformity, as confirmed by using polarizing optical and scanning electron
      microscopy. By raising the CNC concentration in the initial suspension to the
      fully liquid crystalline range, a vertical helix orientation is promoted, as
      directed by the macroscopic phase boundaries. Further control of the helix
      orientation is achieved by subjecting the suspension to a circular shear flow
      during drying. 

PMID- 24677345
TI  - Identification of a critical intermediate in galvanic exchange reactions by
      single-nanoparticle-resolved kinetics.
AB  - The realization of common materials transformations in nanocrystalline systems is
      fostering the development of novel nanostructures and allowing a deep look into
      the atomistic mechanisms involved. Galvanic corrosion is one such transformation.
      We studied galvanic replacement within individual metal nanoparticles by using a
      combination of plasmonic spectroscopy and scanning transmission electron
      microscopy. Single-nanoparticle reaction trajectories showed that a Ag
      nanoparticle exposed to Au3+ makes an abrupt transition into a nanocage
      structure. The transition is limited by a critical structural event, which we
      identified by electron microscopy to comprise the formation of a nanosized void.
      Trajectories also revealed a surprisingly strong nonlinearity of the reaction
      kinetics, which we explain by a model involving the critical coalescence of
      vacancies into a growing void. The critical void size for galvanic exchange to
      spontaneously proceed was found to be 20 atomic vacancies.

PMID- 24677346
TI  - MRI evaluation of the adaptive response of the contralateral kidney following
      nephrectomy in patients with renal cell carcinoma.
AB  - PURPOSE: To study the adaptive responses of the contralateral kidney and its
      association with renal outcome in patients with renal cell carcinoma (RCC)
      following radical nephrectomy (RN). MATERIALS AND METHODS: Eleven patients with
      RCC scheduled for RN and 15 control patients scheduled for adrenalectomy
      (Control) were prospectively recruited. All subjects underwent 4 MRI studies: 1
      before surgery and 3 at 1 week, 1 month and 3 months after surgery, respectively.
      T2-weighted imaging and dynamic contrast-enhanced imaging were performed to
      estimate the renal volume and renal blood flow (RBF) of the contralateral kidney,
      respectively. The patients' serum creatinine levels were examined to determine
      the estimated glomerular filtration rate (e-GFR). The changes in renal volume at
      3 months and both RBF and e-GFR during the serial follow-up were compared and
      associations between both of them were measured in both groups. RESULTS: In the
      RN group, RBF increased at 1 week (2.78 +/- 0.93 mL/min/g, P = 0.002) and 1 month
      (2.65 +/- 0.85 mL/min/g, P = 0.002), compared with presurgical values (1.94 +/-
      0.61 mL/min/g), and it returned to presurgical levels at 3 months (2.11 +/- 0.73
      mL/min/g, P = 0.432). In contrast, e-GFR decreased at 1 week (56.4 +/- 20.3
      mL/min/1.73 m(2) , P = 0.049) and 1 month (52.4 +/- 18.8 mL/min/1.73 m(2) , P =
      0.027), compared with presurgical values (66.3 +/- 18.3 mL/min/1.73 m(2) ), and
      it returned to presurgical levels at 3 months (73.3 +/- 29.5 mL/min/1.73 m(2) , P
      = 0.496). The renal volume increased at 3 months compared with baseline (198 +/-
      87 versus 329 +/- 175 mL, P < 0.001). The change in renal volume was correlated
      with the change in RBF at 1 week (r = 0.609, P = 0.047). CONCLUSION: In patients
      with RCC following RN, an early increase in RBF of the contralateral kidney is
      associated with late renal hypertrophy which might normalize glomerular
      hyperfiltration and restore renal function.

PMID- 24677347
TI  - Evaluation of the Spectra Optia apheresis system for mononuclear cell (MNC)
      collection in G-CSF mobilized and nonmobilized healthy donors: results of a
      multicenter study.
AB  - The Spectra Optia apheresis system is a newer centrifugation-based device that in
      comparison with the COBE Spectra includes features that enhance procedure
      automation and usability. In this FDA-approved three-center two-arm observational
      study we characterized the performance of the Spectra Optia for collection of
      MNCs and CD34+ cells from nonmobilized and granulocyte-colony stimulating factor
      (G-CSF) mobilized healthy donors, respectively. There were a total of 15
      evaluable subjects in each arm. Key performance indicators included collection
      efficiency of MNCs/CD34+ cells, product purity and cellular viability. For
      nonmobilized donors, median MNC collection efficiency, platelet collection
      efficiency, product hematocrit and granulocyte contamination were 57%, 12%, 4%,
      and 1.7%, respectively. For mobilized donors, median MNC collection efficiency,
      CD34+ cell collection efficiency, platelet collection efficiency, product
      hematocrit and granulocyte contamination were 61%, 77%, 19%, 4%, and 15%,
      respectively. Average WBC viability in the mobilized products was 99%. There was
      one severe (grade 3) adverse event related to citrate toxicity. This study
      demonstrates that the Spectra Optia can be used for safe and efficacious
      collection of MNCs, and results obtained are in line with expectations on
      collection efficiency and product characteristics. Adverse events were limited to
      those that are well documented in the stem-cell mobilization and leukapheresis
      process. As of the time of this writing, FDA 510(k) approval for use of the
      Spectra Optia device for MNC collection was achieved in the US based partly on
      the results of this study.

PMID- 24677348
TI  - Layered SnS2-reduced graphene oxide composite--a high-capacity, high-rate, and
      long-cycle life sodium-ion battery anode material.

PMID- 24677350
TI  - High-concentration graphene dispersions with minimal stabilizer: a scaffold for
      enzyme immobilization for glucose oxidation.
AB  - Modified acrylate polymers are able to effectively exfoliate and stabilize
      pristine graphene nanosheets in aqueous media. Starting with pre-exfoliated
      graphite greatly promotes the exfoliation level. The graphene concentration is
      significantly increased up to 11 mg mL(-1) by vacuum evaporation of the solvent
      from the dispersions under ambient temperature. TEM shows that 75 % of the flakes
      have fewer than five layers with about 18 % of the flakes consisting of
      monolayers. Importantly, a successive centrifugation and redispersion strategy is
      developed to enable the formation of dispersions with exceptionally high graphene
      to-stabilizer ratio. Characterization by high-resolution transmission electron
      microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and Raman
      spectroscopy shows the flakes to be of high quality with very low levels of
      defects. These dispersions can act as a scaffold for the immobilization of
      enzymes applied, for example, in glucose oxidation. The electrochemical current
      density was significantly enhanced to be approximately six times higher than an
      electrode in the absence of graphene, thus showing potential applications in
      enzymatic biofuel cells.

PMID- 24677351
TI  - Ultrasmall NaGdF4 nanodots for efficient MR angiography and atherosclerotic
      plaque imaging.

PMID- 24677349
TI  - miRNA sensitivity to Drosha levels correlates with pre-miRNA secondary structure.
AB  - microRNAs (miRNAs) are crucial for cellular development and homeostasis. In order
      to better understand regulation of miRNA biosynthesis, we studied cleavage of
      primary miRNAs by Drosha. While Drosha knockdown triggers an expected decrease of
      many mature miRNAs in human embryonic stem cells (hESC), a subset of miRNAs are
      not reduced. Statistical analysis of miRNA secondary structure and fold change of
      expression in response to Drosha knockdown showed that absence of mismatches in
      the central region of the hairpin, 5 and 9-12 nt from the Drosha cutting site
      conferred decreased sensitivity to Drosha knockdown. This suggests that, when
      limiting, Drosha processes miRNAs without mismatches more efficiently than
      mismatched miRNAs. This is important because Drosha expression changes over
      cellular development and the fold change of expression for miRNAs with mismatches
      in the central region correlates with Drosha levels. To examine the biochemical
      relationship directly, we overexpressed structural variants of miRNA-145, miRNA
      137, miRNA-9, and miRNA-200b in HeLa cells with and without Drosha knockdown; for
      these miRNAs, elimination of mismatches in the central region increased, and
      addition of mismatches decreased their expression in an in vitro assay and in
      cells with low Drosha expression. Change in Drosha expression can be a
      biologically relevant mechanism by which eukaryotic cells control miRNA profiles.
      This phenomenon may explain the impact of point mutations outside the seed region
      of certain miRNAs. 

PMID- 24677352
TI  - Genotoxic and cytotoxic effects of doxorubicin and silymarin on human
      hepatocellular carcinoma cells.
AB  - The aim of this study was to investigate genotoxic and cytotoxic effects of
      doxorubicin, silymarin, or in combination on HepG2 cells for 24 and 48 h. Both
      doxorubicin and silymarin caused dose-dependent inhibition of cell proliferation.
      After 48 h of treatment, doxorubicin application caused dramatically increased
      ratio of apoptotic cells. Both 24 and 48 h of silymarin and doxorubicin-silymarin
      combination caused significant increases in the rate of apoptotic cells.
      Applications of doxorubicin and silymarin separately for 24 h led to
      deoxyribonucleic acid (DNA) damages. After 48 h of incubation, doxorubicin
      induced genotoxic damage was 2-fold higher than the silymarin-induced damage.
      After 24 and 48 h, DNA damage in response to combined applications of doxorubicin
      and silymarin was indifferent from silymarin- and doxorubicin-induced damage
      respectively. There was not any difference in genotoxicity levels between
      incubation periods in combined applications of doxorubicin and silymarin. Lipid
      peroxidation levels increased in all applications. Biopharmacotherapy with
      chemotherapeutic agents are of interest in the issue of adjuvant therapy. Here,
      we demonstrate in vitro potential genotoxic and cytotoxic antitumor effect of
      silymarin on HepG2 cells at achievable plasma level concentrations. 

PMID- 24677353
TI  - Banding of NMR-derived methyl order parameters: implications for protein
      dynamics.
AB  - Our understanding of protein folding, stability, and function has begun to more
      explicitly incorporate dynamical aspects. Nuclear magnetic resonance has emerged
      as a powerful experimental method for obtaining comprehensive site-resolved
      insight into protein motion. It has been observed that methyl-group motion tends
      to cluster into three "classes" when expressed in terms of the popular Lipari
      Szabo model-free squared generalized order parameter. Here the origins of the
      three classes or bands in the distribution of order parameters are examined. As a
      first step, a Bayesian based approach, which makes no a priori assumption about
      the existence or number of bands, is developed to detect the banding of Oaxis2
      values derived either from NMR experiments or molecular dynamics simulations. The
      analysis is applied to seven proteins with extensive molecular dynamics
      simulations of these proteins in explicit water to examine the relationship
      between O2 and fine details of the motion of methyl bearing side chains. All of
      the proteins studied display banding, with some subtle differences. We propose a
      very simple yet plausible physical mechanism for banding. Finally, our Bayesian
      method is used to analyze the measured distributions of methyl group motions in
      the catabolite activating protein and several of its mutants in various liganded
      states and discuss the functional implications of the observed banding to protein
      dynamics and function.

PMID- 24677354
TI  - The heart-rate-reducing agent, ivabradine, reduces mechanical allodynia in a
      rodent model of neuropathic pain.
AB  - BACKGROUND: Peripheral nerve injury increases the excitability of primary sensory
      neurons. This triggers the onset of neuropathic pain and maintains its
      persistence. Because changes in hyperpolarization-activated cyclic nucleotide
      gated cation (HCN) channels are implicated in this process, we examined the
      action of the heart-rate-reducing agent, ivabradine, a clinically approved HCN
      blocker, in the rat chronic constriction injury (CCI) model of neuropathic pain.
      METHODS: The effects of ivabradine on mechanical allodynia were assessed using
      von Frey filaments, and the effects on cardiovascular parameters were monitored
      by telemetry. Ivabradine block of HCN channels in dorsal root ganglion neurons
      was confirmed by whole-cell recording. RESULTS: In rats subject to CCI,
      ivabradine (6 mg/kg by gavage twice a day) significantly reduced mechanical
      allodynia. Cumulative effects were seen with twice daily oral administration over
      a 4-day period. Allodynia returned 4 days after the final drug dose. Mean
      arterial pressure was maintained and only a 15% pharmacological reduction in
      heart rate was observed. There was no cumulative effect of ivabradine on
      cardiovascular parameters. CONCLUSION: Because ivabradine is effective at an oral
      dose that produces only moderate pharmacological heart rate reduction, and this
      is known to be well tolerated in a clinical context, these results underline its
      possible use in neuropathic pain management.

PMID- 24677355
TI  - Sentinel node biopsy for early-stage oral cavity cancer: the VU University
      Medical Center experience.
AB  - BACKGROUND: Sentinel node biopsy (SNB) in head and neck cancer is recently
      introduced as the staging technique of oral squamous cell carcinoma. We report
      the results of SNB in patients diagnosed with a T1-T2 oral squamous cell
      carcinoma and clinically negative (N0) neck in a single center. METHODS: A
      retrospective analysis of 90 previously untreated patients who underwent SNB
      between 2007 and 2012 was performed. The SNB procedure consisted of
      preoperatively performed lymphoscintigraphy, intraoperative detection using blue
      dye, and gamma probe guidance and histopathologic examination including step
      serial sectioning (SSS) and immunohistochemical (IHC) staining. A positive SNB
      was followed by neck dissection, whereas regular follow-up with ultrasound-guided
      fine-needle aspiration cytology (FNAC) was done in case of a negative SNB.
      RESULTS: The lymphoscintigraphic identification rate was 98% (88 of 90 patients)
      and the surgical detection rate was 99% (87 of 88 patients). The upstaging rate
      was 30%. Sensitivity of SNB was 93% and the negative predictive value was 97%.
      The median follow-up was 18 months (range, 2-62 months). Overall survival (OS)
      and disease-free survival (DFS) for SNB negative were 100% and 84% and for SNB
      positive patients 73% and 88%, respectively. CONCLUSION: SNB is a reliable
      diagnostic staging technique for the clinically negative neck in patients with
      early-stage (T1-T2, cN0) oral squamous cell carcinoma.

PMID- 24677356
TI  - Peptide-based carbohydrate receptors.
AB  - A broad spectrum of physiological processes is mediated by highly specific
      noncovalent interactions of carbohydrates and proteins. In a recent communication
      we identified several cyclic hexapeptides in a dynamic combinatorial library that
      interact selectively with carbohydrates with high binding constants in water.
      Herein, we report a detailed investigation of the noncovalent interaction of two
      cyclic hexapeptides (Cys-His-Cys (which we call HisHis) and Cys-Tyr-Cys (which we
      call TyrTyr)) with a selection of monosaccharides and disaccharides in aqueous
      solution. The parallel and antiparallel isomers of HisHis or TyrTyr were
      synthesized separately, and their interaction with monosaccharides and
      disaccharides in aqueous solution was studied by isothermal titration
      calorimetry, NMR spectroscopic titrations, and circular dichroism spectroscopy.
      From these measurements, we identified particularly stable complexes (Ka> 1000 M(
      1)) of the parallel isomer of HisHis with N-acetylneuraminic acid and with methyl
      a-d-galactopyranoside as well as of both isomers of TyrTyr with trehalose. To
      gain further insight into the structure of the peptide-carbohydrate complexes,
      structure prediction was performed using quantum chemical methods. The
      calculations confirm the selectivity observed in the experiments and indicate the
      formation of multiple intermolecular hydrogen bonds in the most stable complexes.

PMID- 24677358
TI  - U-shaped association between serum 25-hydroxyvitamin D and fracture risk in older
      men: results from the prospective population-based CHAMP study.
AB  - The aim of this population-based, prospective, observational study was to examine
      the relationship between serum levels of 25-hydroxyvitamin D (25OHD) and fracture
      risk in a cohort of 1662 community-dwelling men aged 70 to 97 years followed for
      a mean of 4.3 years. Data about mobility, muscle strength, balance, medication
      use, cognition, medical history, lifestyle factors, renal function, and serum
      25OHD were collected at baseline. Data on radiologically verified fractures were
      collected every 4 months. The relationship between fractures and serum 25OHD
      levels was analyzed using Cox's proportional hazard regression. We accounted for
      bone mineral density, falls, physical activity, sun exposure, and season of blood
      draw, in addition to anthropometric and lifestyle factors, medical history,
      muscle strength, balance, and medication and supplement use. There were 123 first
      incident fragility fractures. The relationship between baseline 25OHD and
      fracture risk was U-shaped, with increased fracture risk in men with either low
      or high serum 25OHD levels. In multivariate analysis, the risk of fracture was
      greatest in men with 25OHD levels in the lowest quintile (25OHD <=36 nmol/L;
      hazard ratio [HR] = 3.5; 95% confidence interval [CI] 1.7-7.0) and in men in the
      highest quintile (25OHD >72 nmol/L; HR = 2.7; 95% CI 1.4-5.4) compared with men
      in the 4th quintile (25OHD >=60 to <=72 nmol/L). These associations were not
      explained by lower BMD, increased physical activity, fall risk, or other
      lifestyle or anthropomorphic factors. In community-dwelling older men, there
      appears to be a healthy target range for serum 25OHD concentrations. Thus, serum
      25OHD levels too high and too low may be harmful in regard to fracture risk.

PMID- 24677357
TI  - Redox-triggered C-C coupling of diols and alkynes: synthesis of beta,gamma
      unsaturated alpha-hydroxyketones and furans by ruthenium-catalyzed
      hydrohydroxyalkylation.
AB  - Direct ruthenium-catalyzed CC coupling of alkynes and vicinal diols to form
      beta,gamma-unsaturated ketones occurs with complete levels of regioselectivity
      and good to complete control over the alkene geometry. Exposure of the reaction
      products to substoichiometric quantities of p-toluenesulfonic acid induces
      cyclodehydration to form tetrasubstituted furans. These alkyne-diol
      hydrohydroxyalkylations contribute to a growing body of merged redox-construction
      events that bypass the use of premetalated reagents and, hence, stoichiometric
      quantities of metallic by-products.

PMID- 24677359
TI  - Host-virus interactions: from the perspectives of epigenetics.
AB  - Chromatin structure and histone modifications play key roles in gene regulation.
      Some virus genomes are organized into chromatin-like structure, which undergoes
      different histone modifications facilitating complex functions in virus life
      cycles including replication. Here, we present a comprehensive summary of recent
      research in this field regarding the interaction between viruses and host
      epigenetic factors with emphasis on how chromatin modifications affect viral gene
      expression and virus infection. We also describe the strategies employed by
      viruses to manipulate the host epigenetic program to facilitate virus replication
      as well as the underlying mechanisms. Together, knowledge from this field not
      only generates novel insights into virus life cycles but may also have important
      therapeutic implications.

PMID- 24677360
TI  - Determinants of psychology service utilization in a palliative care outpatient
      population.
AB  - OBJECTIVE: Research has demonstrated that treating cancer patients' psychological
      and physical health leads to improved overall health. This may be especially true
      for palliative care patients facing serious illness. This study examines the
      proportion and determinants of psychology service utilization in an outpatient
      palliative care population. METHODS: Data from an existing clinical database in
      an outpatient palliative clinic utilizing a collaborative care model to deliver
      psychology services were explored. This study was framed by Andersen's Behavioral
      Model of Health Service Use, which incorporates three main components:
      predisposing, enabling, and need factors to model health service utilization. The
      sample (N = 149) was majority middle aged, female, and White with a primary
      diagnosis of cancer. Cross-tabulations were conducted to determine how many
      patients who met screening criteria for depression or anxiety sought psychology
      services. Logistic regression analyses were conducted to assess for predisposing,
      enabling, and need factor determinants of psychology service utilization.
      RESULTS: Among patients who met criteria for moderate depression or anxiety, 50%
      did not access readily available psychology services. Enabling factors were the
      strongest determinant of psychology utilization. Factors associated with need for
      psychology services (i.e., emotional distress and psychological symptom burden)
      did not reach significance in determining psychology service use. CONCLUSIONS:
      This study extends current knowledge about psychology utilization to palliative
      care outpatients receiving care within a collaborative care model. Directions for
      future research include further investigation of care models that optimize
      enabling strategies to enhance access to these services, and examination of
      patient-reported barriers to receiving this care.

PMID- 24677361
TI  - Rational synthesis of triangular Au-Ag(2)S hybrid nanoframes with effective
      photoresponses.
AB  - Triangular Au-Ag2S hybrid nanoframes were successfully synthesised by using Ag
      nanoprisms as templates through gold coating, etching and sulfuration. These Au
      Ag2S hybrid nanoframes exhibit effective photocurrent responses for potential
      photoelectrochemical applications.

PMID- 24677362
TI  - Biosynthesis of phenylnannolone A, a multidrug resistance reversal agent from the
      halotolerant myxobacterium Nannocystis pusilla B150.
AB  - The myxobacterial strain Nannocystis pusilla B150 synthesizes the structurally
      new polyketides phenylnannolone A-C. Apart from some common volatiles and
      siderophores, these are the first natural products from the genus Nannocystis.
      Phenylnannolone A shows inhibitory activity towards the ABCB1 gene product P
      glycoprotein and reverses daunorubicin resistance in cancer cells. To decipher
      the biochemical reactions leading to the formation of phenylnannolone A, the
      putative biosynthetic genes were identified (phn1, phn2). Phn2 is a polyketide
      synthase (PKS) with an NRPS-like loading module, and its domain order is
      consistent with the phenylnannolone A structure. The functionality and substrate
      selectivity of the loading module were determined by means of a gamma-18O4-ATP
      pyrophosphate exchange and a phosphopantetheine ejection assay. A specific
      activation of cinnamic acid by the AMP-ligase was detected. Phn1 is a putative
      butyryl-CoA carboxylase (BCC), providing ethylmalonyl-CoA for the formation of
      the ethyl-substituted part of phenylnannolone A. Phn1 is the first BCC found in
      biosynthetic genes for an ethyl-substituted natural compound. Biosynthesis of
      phenylnannolone A, putatively encoded by phn1 and phn2, thus utilizes the first
      biosynthetic machinery in which both a BCC and a PKS are involved.

PMID- 24677363
TI  - Effect of external voltage on Pseudomonas putida F1 in a bio electrochemical cell
      using toluene as sole carbon and energy source.

PMID- 24677364
TI  - Techniques and best practices for optical coherence tomography: a practical
      manual for interventional cardiologists.
AB  - Optical coherence tomography (OCT) is a novel intracoronary imaging modality that
      utilizes near-infrared light to provide information regarding lesion length and
      severity, vessel lumen diameter, plaque morphology, as well as the opportunity
      for stent procedure guidance and follow-up. While analogous to intravascular
      ultrasound (IVUS), the specific imaging properties, including significantly
      higher resolution, and technical specifications of OCT offer the ability for
      intracoronary diagnostic and interventional procedure guidance roles that require
      a thorough understanding of the technology. We provide coronary
      interventionalist's a user's guide to OCT, focusing on techniques and approaches
      to optimize imaging, with a focus on efficiency, safety and strategies for
      effective imaging.

PMID- 24677365
TI  - The active layer morphology of organic solar cells probed with grazing incidence
      scattering techniques.
AB  - Grazing incidence X-ray scattering (GIXS) provides unique insights into the
      morphology of active materials and thin film layers used in organic photovoltaic
      devices. With grazing incidence wide angle X-ray scattering (GIWAXS) the
      molecular arrangement of the material is probed. GIWAXS is sensitive to the
      crystalline parts and allows for the determination of the crystal structure and
      the orientation of the crystalline regions with respect to the electrodes. With
      grazing incidence small angle X-ray scattering (GISAXS) the nano-scale structure
      inside the films is probed. As GISAXS is sensitive to length scales from
      nanometers to several hundred nanometers, all relevant length scales of organic
      solar cells are detectable. After an introduction to GISAXS and GIWAXS, selected
      examples for application of both techniques to active layer materials are
      reviewed. The particular focus is on conjugated polymers, such as poly(3
      hexylthiophene) (P3HT). 

PMID- 24677366
TI  - Self-organized learning environments and the future of student-centered
      education.

PMID- 24677367
TI  - Problem-solving test: transport of a viral protein in a cell-free system.
AB  - Terms to be familiar with before you start to solve the test: protein
      glycosylation, glycoprotein, endoplasmic reticulum, Golgi complex, mannose,
      oligosaccharide, free polysomes, cell fractionation, [(35) S]methionine; pulse
      labeling; nuclear fraction, mitochondrial fraction, microsomal fraction, cytosol,
      gel electrophoresis, autoradiography, trypsin, deoxycholate, detergent, sucrose
      density gradient, isopycnic gradient centrifugation.

PMID- 24677368
TI  - Commentary: learning analytics: ephemeral rhetoric or valuable approach?

PMID- 24677369
TI  - Websites of note.

PMID- 24677370
TI  - Nanoliter-droplet acoustic streaming via ultra high frequency surface acoustic
      waves.
AB  - The relevant length scales in sub-nanometer amplitude surface acoustic wave
      driven acoustic streaming are demonstrated. We demonstrate the absence of any
      physical limitations preventing the downscaling of SAW-driven internal streaming
      to nanoliter microreactors and beyond by extending SAW microfluidics up to
      operating frequencies in the GHz range. This method is applied to nanoliter scale
      fluid mixing. 

PMID- 24677371
TI  - Instantaneous signal loss simulation (InSiL): an improved algorithm for
      myocardial T1 mapping using the MOLLI sequence.
AB  - PURPOSE: To propose a T1 mapping algorithm for the modified Look-Locker inversion
      recovery (MOLLI) sequence that can improve T1 estimation accuracy. MATERIALS AND
      METHODS: The modified T1 mapping algorithm (InSiL) is based on the simulation of
      MOLLI signal evolution and simulates the longitudinal magnetization signal
      perturbation by each single-shot image acquisition in MOLLI as an instantaneous
      signal loss. InSiL was evaluated against original MOLLI using Bloch simulations,
      phantom studies, and in 15 healthy volunteers at 1.5T. RESULTS: In phantom
      studies, the maximum absolute error by InSiL is less than 2%, while that by MOLLI
      is more than 20% for T1 values from 221 msec to 1539 msec. The benefit of InSiL
      is greatest at heart rate (HR) >80 bpm and T1 >1000 msec, and InSiL reduced MOLLI
      T1 error from 14.9 +/- 4.5% to 0.4 +/- 0.3%. Average InSiL-derived native
      myocardial T1 values at 1.5T in healthy volunteers were significantly higher than
      MOLLI-derived values by 236.9 +/- 11.7 msec (1160.3 +/- 25.1 msec vs. 923.4 +/-
      22.3 msec, P < 0.001) at an average HR of 65.1 +/- 14.7 bpm. CONCLUSION: The
      proposed InSiL approach yields better T1 mapping accuracy than MOLLI, and is less
      sensitive to HR variation in tissues with longer T1 values.

PMID- 24677372
TI  - Comparative analysis of sequence covariation methods to mine evolutionary hubs:
      examples from selected GPCR families.
AB  - Covariation between positions in a multiple sequence alignment may reflect
      structural, functional, and/or phylogenetic constraints and can be analyzed by a
      wide variety of methods. We explored several of these methods for their ability
      to identify covarying positions related to the divergence of a protein family at
      different hierarchical levels. Specifically, we compared seven methods on a model
      system composed of three nested sets of G-protein-coupled receptors (GPCRs) in
      which a divergence event occurred. The covariation methods analyzed were based
      on: chi2 test, mutual information, substitution matrices, and perturbation
      methods. We first analyzed the dependence of the covariation scores on residue
      conservation (measured by sequence entropy), and then we analyzed the networking
      structure of the top pairs. Two methods out of seven--OMES (Observed minus
      Expected Squared) and ELSC (Explicit Likelihood of Subset Covariation)--favored
      pairs with intermediate entropy and a networking structure with a central residue
      involved in several high-scoring pairs. This networking structure was observed
      for the three sequence sets. In each case, the central residue corresponded to a
      residue known to be crucial for the evolution of the GPCR family and the
      subfamily specificity. These central residues can be viewed as evolutionary hubs,
      in relation with an epistasis-based mechanism of functional divergence within a
      protein family.

PMID- 24677373
TI  - Molecular mechanisms of bone metastasis and associated muscle weakness.
AB  - Bone is a preferred site for breast cancer metastasis and leads to pathologic
      bone loss due to increased osteoclast-induced bone resorption. The homing of
      tumor cells to the bone depends on the support of the bone microenvironment in
      which the tumor cells prime the premetastatic niche. The colonization and growth
      of tumor cells then depend on adaptations in the invading tumor cells to take
      advantage of normal physiologic responses by mimicking bone marrow cells. This
      concerted effort by tumor cells leads to uncoupled bone remodeling in which the
      balance of osteoclast-driven bone resorption and osteoblast-driven bone
      deposition is lost. Breast cancer bone metastases often lead to osteolytic
      lesions due to hyperactive bone resorption. Release of growth factors from bone
      matrix during resorption then feeds a "vicious cycle" of bone destruction leading
      to many skeletal-related events. In addition to activity in bone, some of the
      factors released during bone resorption are also known to be involved in skeletal
      muscle regeneration and contraction. In this review, we discuss the mechanisms
      that lead to osteolytic breast cancer bone metastases and the potential for
      cancer-induced bone-muscle cross-talk leading to skeletal muscle weakness.

PMID- 24677374
TI  - Genetic modification of T cells redirected toward CS1 enhances eradication of
      myeloma cells.
AB  - PURPOSE: Our goal is to test whether CS1 could be targeted by chimeric antigen
      receptor (CAR) T cells to treat multiple myeloma (MM). EXPERIMENTAL DESIGN: We
      generated a retroviral construct of a CS1-specific CAR and engineered primary
      human T cells expressing the CAR. We then tested the capacity of CS1-CAR T cells
      to eradicate human MM tumor cells in vitro, ex vivo, and in vivo using orthotopic
      MM xenograft mouse models. RESULTS: In vitro, compared with mock-transduced T
      cells, upon recognizing CS1-positive MM cells, CS1-CAR-transduced T cells
      secreted more IFN-gamma as well as interleukin (IL)-2, expressed higher levels of
      the activation marker CD69, showed higher capacity for degranulation, and
      displayed enhanced cytotoxicity. Ectopically forced expression of CS1 in MM cells
      with low CS1 expression enhanced recognition and killing by CAR T cells. Ex vivo,
      CS1-CAR T cells also showed similarly enhanced activities when responding to
      primary MM cells. More importantly, in orthotopic MM xenograft mouse models,
      adoptive transfer of human primary T cells expressing CS1-CAR efficiently
      suppressed the growth of human MM.1S and IM9 myeloma cells and significantly
      prolonged mouse survival. CONCLUSIONS: CS1 is a promising antigen that can be
      targeted by CAR-expressing T cells for treatment of MM.

PMID- 24677375
TI  - Interleukin-17A modulates circulating tumor cells in tumor draining vein of
      colorectal cancers and affects metastases.
AB  - PURPOSE: Metastasis is the major cause of death in patients with colorectal
      cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and
      serve as a prognostic marker for mortality in clinical stage IV patients.
      However, most studies are conducted in late-stage cases when distant metastases
      have already occurred; thus, such results provide limited clinical use. This
      study focused on whether CTCs can predict the risk of metastasis after treatment
      of the primary tumor in early-stage patients with CRC. EXPERIMENTAL DESIGN: CTCs
      were quantified using EpCAM-positive/CD45-negative immunoselection and flow
      cytometry in patients with CRC. A mouse model was used to investigate the
      mechanistic roles of CTCs and interleukin (IL)-17A in metastasis. RESULTS: The
      number of mesenteric CTCs obtained from stage II patients was higher than that
      obtained from patients in stages I, III, and IV. In addition, following invasion
      of orthotopically implanted tumors in our mouse model, we found that CTCs
      exhibited an increase-then-decrease pattern, accompanied by corresponding changes
      in serum IL-17A levels and opposing changes in serum granulocyte macrophage
      colony-stimulating factor (GM-CSF) levels. Ablation of IL-17A and administration
      of rGM-CSF effectively suppressed the increase in CTCs and prevented metastasis
      in mice. Moreover, IL-17A promoted cancer cell motility, matrix digestion, and
      angiogenesis, whereas GM-CSF stimulated the elimination of CTCs by boosting host
      immunity. Notably, serum levels of IL-17A were also correlated with disease-free
      survival in patients with CRC. CONCLUSIONS: Our results showed that CTCs and IL
      17A could serve as prognostic markers and therapeutic targets for CRC metastasis.
      Clin Cancer Res; 20(11); 2885-97. (c)2014 AACR.

PMID- 24677377
TI  - Morbidities after maxillary swing nasopharyngectomy for recurrent nasopharyngeal
      carcinoma.
AB  - BACKGROUND: The purpose of this study was to investigate the complications after
      maxillary swing nasopharyngectomy. METHODS: Salvage nasopharyngectomy was
      performed for 338 patients during 1990 to 2012. Patient and tumor
      characteristics, perioperative and intraoperative information, and long-term
      morbidities were analyzed. RESULTS: There were significantly more patients with
      locally advanced tumors (rT3 and rT4) operated during the recent study period
      (2002-2012). However, the mean operative time and blood loss was significantly
      lower than in the earlier period (1990-2001). There was no hospital mortality.
      There was a significant reduction in the postoperative trismus and palatal
      fistula formation. Patients with locally advanced tumor, particularly those who
      required adjuvant chemoradiation, had a higher chance of facial numbness, nasal
      blockage, and swallowing problems after surgery. CONCLUSION: Salvage
      nasopharyngectomy via the maxillary swing approach is safe with acceptable long
      term morbidities. Prevention of complications associated with surgery,
      particularly for patients with locally advanced tumors, is crucial to ensure the
      best outcome of surgery.

PMID- 24677378
TI  - Solution to recurrent suprahepatic caval stenosis after liver transplantation:
      cardiac surgery after repeated dilatations and stenting.

PMID- 24677376
TI  - Structural biology of the IL-1 superfamily: key cytokines in the regulation of
      immune and inflammatory responses.
AB  - Interleukin-1 superfamily of cytokines (IL-1, IL-18, IL-33) play key roles in
      inflammation and regulating immunity. The mechanisms of agonism and antagonism in
      the IL-1 superfamily have been pursued by structural biologists for nearly 20
      years. New insights into these mechanisms were recently provided by the crystal
      structures of the ternary complexes of IL-1beta and its receptors. We will review
      here the structural biology related to receptor recognition by IL-1 superfamily
      cytokines and the regulation of its cytokine activities by antagonists. 

PMID- 24677379
TI  - Differential antinociceptive effects of intrathecal administration of C-terminal
      esterified endomorphin-2 analogues in mice.
AB  - BACKGROUND: We have previously synthesized three esterified endomorphin-2 (EM-2)
      analogues 1-3 by substitution of C-terminus with methyl, ethyl and tert-butyl
      ester, respectively. Interestingly, the increase of EM-2 in bulkness of the
      esterified group decreased the MU-opioid receptor affinity but increased the
      delta-affinity. Presently, we extended our studies to investigate the
      antinociceptive potencies of these esterified analogues given intrathecally in
      the mouse tail-flick test. Also, the specific opioid receptor antagonists and
      antibodies against endogenous opioid peptides were used to determine whether
      there are any differential mechanisms on the antinociception produced by these
      analogues. METHODS: Antinociception was assessed using the 50  degrees C hot
      water tail-flick test. The drugs and antibodies were administered intrathecally.
      RESULTS: The ED50 value of analogue 1 was 1.34 nmol, exhibiting the highest
      analgesic effect. In contrast, the antinociceptive potency of analogue 2 was
      about twofold less potent than that of EM-2. The antinociception induced by
      analogues 1 and 2 was mediated by the stimulation of MU-opioid receptor in the
      spinal cord. However, the analogue 1-induced antinociception also contained an
      additional component that was mediated by the release of dynorphin A acting on
      kappa-opioid receptor, which was similar to its parent EM-2. Notably, analogue 3
      exhibited only slightly lower analgesia relative to EM-2, which may possibly be
      due to a direct stimulation of both MU- and delta-opioid receptors. CONCLUSIONS:
      Our results demonstrated that EM-2 and its analogues 1-3 produced differential
      antinociceptive effects when administered intrathecally. We concluded that C
      terminal amide to esterification conversion changed the antinociceptive potencies
      and properties of EM-2.

PMID- 24677380
TI  - Silicon-directed rhenium-catalyzed allylic carbaminations and oxidative
      fragmentations of gamma-silyl allylic alcohols.
AB  - A highly regioselective allylic substitution of beta-silyl allylic alcohols has
      been achieved that provides the branched isomer as a single product. This high
      level of regiocontrol is achieved through the use of a vinyl silane group that
      can perform a Hiyama coupling providing 1,3-disubstituted allylic amines. An
      unusual oxidative fragmentation product was also observed at elevated temperature
      that appears to proceed by a Fleming-Tamao-type oxidation-elimination pathway. 

PMID- 24677381
TI  - Optically active tetra-tert-butyl-P(5)-deltacyclene epimers: preparation,
      spectroscopy, dynamic equilibriums, H/D exchange, and transition-metal complex
      chemistry.
AB  - On the basis of isolated diastereomeric triorganylstannyl-P5 -deltacyclenes 7'
      and 7'', almost pure enantiomers of their destannylation products 8' and 8'' are
      now available. These stereochemically inert cage chiral species contain a
      configurationally labile P1?H1 group that defines two epimers 8 a and 8 b of each
      of the enantiomers, which are connected by a rapid equilibrium. Mirror-symmetric
      circular dichroism (CD) spectra of the enantiomeric cages are compatible with the
      identification of epimers. A simulation of the CD spectrum of the major epimer
      8'a relates the cage chirality of the system to the observed chiroptical effects.
      Both cage epimers and two of the phosphorus cage atoms are active as ligands with
      respect to [M(CO)5 ] fragments of Cr, Mo, and W. Four almost isoenergetic regio-
      and stereoisomers of the resulting mononuclear complexes are formed for these
      metals, but only one of the isomers per metal crystallized in the case of the
      racemic series of the complexes. The enantiopure versions of cages and cage
      complexes, however, did not crystallize at all, a well-known phenomenon for
      chiral compounds. CD spectra of the optically active complex isomer mixtures are
      close to identical with the CD spectra of the related free cages and point again
      to the chiral cages as the dominant source of the CD effects of the complexes.
      [(Benzene)RuCl2 ] complexes of the cage ligand 8 behave totally differently. Only
      a single species 12=[(benzene)RuCl2 ?8 b] is formed in almost quantitative yield
      and the minor epimer 8 b plays the role of the ligand exclusively. The reaction
      works as well for the separated enantiomeric cage versions to yield the highly
      enriched enantiomers 12' and 12'' separately. An efficient kinetic resolution
      process was identified as the main reason for this finding. It is based on a high
      stereo- and regiochemical flexibility of the P?C cage ligand that is capable of
      adjusting to the specific requirements of a suitable transition-metal complex
      fragment. Such ligand flexibility is regularly observed in metalloenzymes, but is
      a very rare case in classical and organometallic complex chemistry.

PMID- 24677382
TI  - Divergent phenological response to hydroclimate variability in forested mountain
      watersheds.
AB  - Mountain watersheds are primary sources of freshwater, carbon sequestration, and
      other ecosystem services. There is significant interest in the effects of climate
      change and variability on these processes over short to long time scales. Much of
      the impact of hydroclimate variability in forest ecosystems is manifested in
      vegetation dynamics in space and time. In steep terrain, leaf phenology responds
      to topoclimate in complex ways, and can produce specific and measurable shifts in
      landscape forest patterns. The onset of spring is usually delayed at a specific
      rate with increasing elevation (often called Hopkins' Law; Hopkins, 1918),
      reflecting the dominant controls of temperature on greenup timing. Contrary with
      greenup, leaf senescence shows inconsistent trends along elevation gradients.
      Here, we present mechanisms and an explanation for this variability and its
      significance for ecosystem patterns and services in response to climate. We use
      moderate-resolution imaging spectro-radiometer (MODIS) Normalized Difference
      Vegetation Index (NDVI) data to derive landscape-induced phenological patterns
      over topoclimate gradients in a humid temperate broadleaf forest in southern
      Appalachians. These phenological patterns are validated with different sets of
      field observations. Our data demonstrate that divergent behavior of leaf
      senescence with elevation is closely related to late growing season hydroclimate
      variability in temperature and water balance patterns. Specifically, a drier late
      growing season is associated with earlier leaf senescence at low elevation than
      at middle elevation. The effect of drought stress on vegetation senescence timing
      also leads to tighter coupling between growing season length and ecosystem water
      use estimated from observed precipitation and runoff generation. This study
      indicates increased late growing season drought may be leading to divergent
      ecosystem response between high and low elevation forests. Landscape-induced
      phenological patterns are easily observed over wide areas and may be used as a
      unique diagnostic for sources of ecosystem vulnerability and sensitivity to
      hydroclimate change. 

PMID- 24677383
TI  - Patient perspectives on the Hula Empowering Lifestyle Adaptation Study: benefits
      of dancing hula for cardiac rehabilitation.
AB  - BACKGROUND: The Hula Empowering Lifestyle Adaption Study, funded by the National
      Institute on Minority Health and Health Disparities, was a 5-year research trial
      evaluating the impact of the traditional Native Hawaiian dance form, hula, as an
      exercise modality for cardiac rehabilitation, compared with usual care, on
      individuals recently hospitalized for a cardiac event or who had recently
      undergone coronary artery bypass surgery. METHOD AND RESULTS: Seeking to learn
      what physical, mental, spiritual, and social effects the intervention may have
      had for participants, we interviewed 20 of a total of 35 patients who were
      enrolled in the dance arm of the study. Classical thematic triangulation analysis
      was used. Participants recognized that hula's coordination of body, mind, and
      spirit as a group activity deepened their appreciation of and connections to
      Hawaiian culture. This was true for those who were Native Hawaiian, connecting to
      their own cultural heritage, as well as for non-Native Hawaiians, who found that
      it improved their appreciation of the surrounding cultural traditions of the host
      culture where they now live. CONCLUSIONS: Not only was hula a safe activity that
      improved functional capacity, participants also regarded its significant
      sociocultural aspects-even for participants who are not Native Hawaiian -as
      enhancing its value and meaningfulness. Learning the words of well-known Hawaiian
      songs provided additional long-term cues that encouraged "ownership" of the
      therapy and acted as practical reminders of the importance of exercise and
      lifestyle moderation while also offering new spiritual connections to the
      surrounding social environment.

PMID- 24677384
TI  - Reproducibility and reliability of short-TE whole-brain MR spectroscopic imaging
      of human brain at 3T.
AB  - PURPOSE: A feasibility study of an echo-planar spectroscopic imaging (EPSI) using
      a short echo time (TE) that trades off sensitivity, compared with other short-TE
      methods, to achieve whole brain coverage using inversion recovery and spatial
      oversampling to control lipid bleeding. METHODS: Twenty subjects were scanned to
      examine intersubject variance. One subject was scanned five times to examine
      intrasubject reproducibility. Data were analyzed to determine coefficients of
      variance (COV) and intraclass correlation coefficient (ICC) for N-acetylaspartate
      (NAA), total creatine (tCr), total choline (tCho), glutamine/glutamate (Glx), and
      myo-inositol (mI). Regional metabolite concentrations were derived by using multi
      voxel analysis based on lobar-level anatomic regions. RESULTS: For whole-brain
      mean values, the intrasubject COVs were 14%, 15%, and 20% for NAA, tCr, and tCho,
      respectively, and 31% for Glx and mI. The intersubject COVs were up to 6% higher.
      For regional distributions, the intrasubject COVs were <= 5% for NAA, tCr, and
      tCho; <= 9% for Glx; and <=15% for mI, with about 6% higher intersubject COVs.
      The ICCs of 5 metabolites were >= 0.7, indicating the reliability of the
      measurements. CONCLUSION: The present EPSI method enables estimation of the whole
      brain metabolite distributions, including Glx and mI with small voxel size, and a
      reasonable scan time and reproducibility.

PMID- 24677385
TI  - Novel-porous-Ag0 nanocomposite hydrogels via green process for advanced
      antibacterial applications.
AB  - Silver nanoparticles (NPs) antibacterial characteristics were depends on its
      particle stabilization, particles size and nucleation agent. In this study, we
      report on green process of porous silver nanocomposite hydrogels for advanced
      antibacterial applications. The porous poly(acrylamide) (PAM) hydrogels were
      developed employing sucrose as porogenator. Silver NPs were nucleated with
      natural biomass Neem (Azadirachta indica) leaf extracts within the porous
      hydrogel networks. The formation of silver NPs in the porous hydrogels was
      confirmed by ultraviolet-visible spectroscopy, fourier transform infrared
      spectroscopy, X-ray diffraction, and thermo gravimetric analysis. Morphological
      studies done by scanning electron microscopy and transmission electron microscopy
      showed that the hydrogels were porous in nature and stabilization of NPs, size,
      and particles shape. The porous PAM silver nanoparticle hydrogels demonstrated
      excellent antimicrobial activity with significant effect against Escherichia
      coli, Micrococcus, and Candida albicus. Hence, it was clear that the developed
      hydrogels can be used effectively for preventing and treating infections.

PMID- 24677386
TI  - Application and future challenges of functional nanocarbon hybrids.
AB  - Hybridizing nanocarbons, such as carbon nanotubes (CNTs) or graphene, with an
      active material is a powerful strategy towards designing next-generation
      functional materials for environmental and sustainable energy applications. While
      research on nanocomposites, created by dispersing the nanocarbon into polymer or
      ceramic matrices, began almost immediately after the popularization of CNTs and
      graphene in 1991 and 2004, respectively, nanocarbon hybrids are a relatively
      recent addition to the family of composite materials. In contrast to
      nanocomposites, which typically combine the intrinsic properties of both
      compounds, nanocarbon hybrids additionally provide access to both a large surface
      area required for gas/liquid-solid interactions and an extended interface,
      through which charge and energy transfer processes create synergistic effects
      that result in unique properties and superior performance. This progress report
      looks at the history of research on nanocarbons (fullerenes, CNTs and graphene)
      and their composites and hybrids, presents the origin of synergistic effects,
      reviews the most intriguing results on nanocarbon hybrid performance in
      heterogeneous catalysis, electrocatalysis, photocatalysis, batteries,
      supercapacitors, photovoltaics and sensors, and discusses remaining challenges
      and future research directions. 

PMID- 24677387
TI  - Chemiluminescence accompanied by the reaction of acridinium ester and manganese
      (II).
AB  - An acridinium ester (AE) alkaline solution can react with Mn(II) to generate a
      strong chemiluminescence (CL) centered at 435 nm. The effects of reaction
      conditions such as pH and Mn(II) concentration on CL intensity were examined. In
      order to explore the CL mechanism, the effect of oxygen on the CL reaction was
      examined and an X-ray photoelectron spectroscopy study of the reaction
      precipitate was carried out. The results indicated that oxygen participated in
      the CL reaction and Mn(IV) was the primary product in the system. A possible
      mechanism was proposed that involved two pathways: (1) dissolved oxygen was
      reduced to reactive oxygen radicals by Mn(II), these reactive intermediates then
      reacted with AE to produce excited state acridone; (2) Mn(II) could reduce AE to
      partly reduced AE, which then reacted with oxygen to form excited state acridone.
      The reactions of other metal ions with AE were also tested, and only Mn(II) was
      shown to trigger strong CL emission of AE, which indicated that the system had
      good selectivity for Mn(II).

PMID- 24677388
TI  - On the mechanism of bifunctional squaramide-catalyzed organocatalytic Michael
      addition: a protonated catalyst as an oxyanion hole.
AB  - A joint experimental-theoretical study of a bifunctional squaramide-amine
      catalyzed Michael addition reaction between 1,3-dioxo nucleophiles and
      nitrostyrene has been undertaken to gain insight into the nature of bifunctional
      organocatalytic activation. For this highly stereoselective reaction, three
      previously proposed mechanistic scenarios for the critical C?C bond-formation
      step were examined. Accordingly, the formation of the major stereoisomeric
      products is most plausible by one of the bifunctional pathways that involve
      electrophile activation by the protonated amine group of the catalyst. However,
      some of the minor product isomers are also accessible through alternative
      reaction routes. Structural analysis of transition states points to the
      structural invariance of certain fragments of the transition state, such as the
      protonated catalyst and the anionic fragment of approaching reactants. Our
      topological analysis provides deeper insight and a more general understanding of
      bifunctional noncovalent organocatalysis. 

PMID- 24677389
TI  - Transparent flexible graphene triboelectric nanogenerators.

PMID- 24677390
TI  - Autoamplification of molecular chirality through the induction of supramolecular
      chirality.
AB  - The novel concept for the autoamplification of molecular chirality, wherein the
      amplification proceeds through the induction of supramolecular chirality, is
      presented. A solution of prochiral, ring-open diarylethenes is doped with a small
      amount of their chiral, ring-closed counterpart. The molecules co-assemble into
      helical fibers through hydrogen bonding and the handedness of the fibers is
      biased by the chiral, ring-closed diarylethene. Photochemical ring closure of the
      open diarylethene yields the ring-closed product, which is enriched in the
      template enantiomer. 

PMID- 24677391
TI  - Image quality versus outcomes.

PMID- 24677392
TI  - Anticancer potency studies of coordination driven self-assembled arene-Ru-based
      metalla-bowls.
AB  - New tetranuclear cationic metalla-bowls 5-7 with the general formula [Ru4(p
      cymene)4(N?N)2(OO?OO)2]4+ (N?N=2,6-bis(N-(4-pyridyl carbamoyl)pyridine, OO?OO=2,5
      dihydroxy-1,4-benzoquinonato (5), OO?OO=5,8-dioxydo-1,4-naphthaquinonato (6),
      OO?OO=hoxonato (7)) were prepared by the reaction of the respective dinuclear
      ruthenium complexes 2-4 with a bispyridine amide donor ligand 1 in methanol in
      the presence of AgO3SCF3.These new molecular metalla-bowls were fully
      characterized by analytical techniques including elemental analysis as well as 1H
      and 13C NMR and HR-ESI-MS spectroscopy. The structure of metalla-bowl 6 was
      determined from X-ray crystal diffraction data. A UV/visible study was also
      carried out for the entire suite of new complexes. As with recent studies of
      similar arene-Ru complexes, the inhibition of cell growth by metalla-bowls was
      established against SK-hep-1 (liver cancer), AGS (gastric cancer), and HCT-15
      (colorectal cancer) human cancer cell lines. Inhibition of cell growth by 6 was
      found to be considerably stronger against all cancer cell lines than the
      anticancer drugs, doxorubicin and cisplatin. In particular, in colorectal cancer
      cells, expression of the cancer suppressor genes APC and p53 was increased
      following exposure to 6.

PMID- 24677393
TI  - Acoustic propulsion of nanorod motors inside living cells.
AB  - The ultrasonic propulsion of rod-shaped nanomotors inside living HeLa cells is
      demonstrated. These nanomotors (gold rods about 300 nm in diameter and about 3 mm
      long) attach strongly to the external surface of the cells, and are readily
      internalized by incubation with the cells for periods longer than 24 h. Once
      inside the cells, the nanorod motors can be activated by resonant ultrasound
      operating at 4 MHz, and show axial propulsion as well as spinning. The
      intracellular propulsion does not involve chemical fuels or high-power ultrasound
      and the HeLa cells remain viable. Ultrasonic propulsion of nanomotors may thus
      provide a new tool for probing the response of living cells to internal
      mechanical excitation, for controllably manipulating intracellular organelles,
      and for biomedical applications.

PMID- 24677394
TI  - Navigating healthcare: a qualitative study exploring prostate cancer patients'
      and doctors' experience of consultations using a decision-support intervention.
AB  - BACKGROUND: Men with prostate cancer face preference-sensitive decisions when
      choosing among treatments with similar survival outcomes but different
      procedures, risks and potential complications. A decision-support intervention,
      'Decision Navigation' assists men with prostate cancer to prepare a question list
      (consultation plan) for their doctors and provides them with a consultation
      summary and audio recording. A randomised controlled trial of Decision Navigation
      showed advantages over usual care on quantitative measures including confidence
      in decision-making and regret. OBJECTIVE: The aim of this study was to gain a
      qualitative understanding of patient's and doctor's perspectives on Decision
      Navigation. METHODS: Six patients who received Decision Navigation were
      purposively selected for interview out of 62 randomised controlled trial
      participants. All four doctors who consulted Navigated patients were interviewed.
      Interview data was analysed using framework analysis. RESULTS: Patients reported
      that planning for the consultation helped them to frame their questions, enabling
      them to participate in consultations and take responsibility for making
      decisions. They reported feeling more confident in the decisions made, having a
      written report of the key information and an audio recording. Patients considered
      routine information relating to side effects was inadequate. Doctors reported
      that consultation plans made them aware of patients' concerns and ensured
      comprehensive responses to questions posed. Doctors also endorsed implementing
      Decision Navigation as part of routine care. CONCLUSION: Results suggest that
      Decision Navigation facilitated patients' involvement in treatment decision
      making. Prostate patients engaging in preference-sensitive decision-making
      welcomed this approach to personalised tailored support.

PMID- 24677395
TI  - Ruthenium(II)-catalyzed synthesis of isochromenes by C-H activation with weakly
      coordinating aliphatic hydroxyl groups.
AB  - Cationic ruthenium(II) complexes have been employed for the highly effective
      oxidative annulation of alkynes with benzyl alcohols to deliver diversely
      decorated isochromenes. The hydroxyl-directed C-H/O-H functionalization process
      proceeded efficiently under an atmosphere of air. Detailed mechanistic studies
      were indicative of a kinetically relevant C-H metalation.

PMID- 24677396
TI  - Crystal structure of JHP933 from Helicobacter pylori J99 shows two-domain
      architecture with a DUF1814 family nucleotidyltransferase domain and a helical
      bundle domain.
AB  - The jhp0933 gene in the plasticity region of Helicobacter pylori J99 encodes a
      hypothetical protein (JHP933), which may play some roles in pathogenesis. Here,
      we have determined the crystal structure of JHP933 at 2.17 A. It represents the
      first crystal structure of the DUF1814 protein family. JHP933 consists of two
      domains: an N-terminal domain of the nucleotidyltransferase (NTase) fold and a C
      terminal helix bundle domain. A highly positively charged surface patch exists
      adjacent to the putative NTP binding site. Structural similarity of JHP933 to
      known NTases is very remote, suggesting that it may function as a novel NTase.

PMID- 24677397
TI  - New anti-complement drugs: not so far away.
AB  - In this issue of Blood, Risitano et al demonstrate that small-molecule inhibitors
      of C3 cleavage prevent complement activation on erythrocytes from patients with
      paroxysmal nocturnal hemoglobinuria (PNH); the authors demonstrate that these
      agents reach therapeutic concentrations after subcutaneous injection in nonhuman
      primates.

PMID- 24677398
TI  - Shedding light on the asparaginase galaxy.
AB  - In this issue of Blood, Tong et al have reported that therapeutic drug monitoring
      (TDM) of asparaginase (ASP) activity levels in plasma may be an important tool
      for the optimization of its therapeutic effects in pediatric acute lymphoblastic
      leukemia (ALL).

PMID- 24677399
TI  - Why do T cells cause so much trouble?
AB  - In this issue of Blood, Price et al document a 20-year experience with autoimmune
      lymphoproliferative syndrome (ALPS) patients and healthy mutation-positive
      relatives, showing that defective lymphocyte apoptosis is associated with an
      increased incidence of lymphomas.

PMID- 24677400
TI  - Cyclin D1 transcriptional activation in MCL.
AB  - In this issue of Blood, Allinne et al propose the nucleolin-dependent activation
      of the translocated CCND1 allele in mantle cell lymphoma (MCL) because of its
      relocalization to a transcriptionally favorable area in the perinucleolar region.

PMID- 24677401
TI  - How do estrogens control lymphoma?
AB  - In this issue of Blood, Yakimchuk and colleagues show that estrogen receptor beta
      (ERbeta) signaling can act tumor-suppressive predominantly through the regulation
      of genes by ERbeta in the tumor, not in the microenvironment, and point out new
      therapeutic strategies.

PMID- 24677402
TI  - Increasing therapeutic efficacy in MPN.
AB  - In this issue of Blood, Bhagwat et al describe an elegant series of experiments
      showing that genetic deletion in the hematopoietic system of Janus kinase 2
      (JAK2) abrogates initiation of myeloproliferative disease and substantial disease
      regression if deleted once disease is initiated.

PMID- 24677403
TI  - A dual regulator of neutrophil recruitment.
AB  - In this issue of Blood, Boespflug et al report that activating transcription
      factor 3 (ATF3), a member of the ATF/cyclic AMP response element-binding
      (ATF/CREB) family of transcription factors, plays a crucial role in regulating
      neutrophil recruitment during lung inflammation.

PMID- 24677404
TI  - Charge-transfer complex formation in gelation: the role of solvent molecules with
      different electron-donating capacities.
AB  - A naphthalenediimide (NDI)-based synthetic peptide molecule forms gels in a
      particular solvent mixture (chloroform/aromatic hydrocarbon, 4:1) through charge
      transfer (CT) complex formation; this is evident from the corresponding
      absorbance and fluorescence spectra at room temperature. Various aromatic
      hydrocarbon based solvents, including benzene, toluene, xylene (ortho, meta and
      para) and mesitylene, have been used for the formation of the CT complex. The
      role of different solvent molecules with varying electron-donation capacities in
      the formation of CT complexes has been established through spectroscopic and
      computational studies. 

PMID- 24677405
TI  - Mechanisms underpinning climatic impacts on natural populations: altered species
      interactions are more important than direct effects.
AB  - Shifts in species' distribution and abundance in response to climate change have
      been well documented, but the underpinning processes are still poorly understood.
      We present the results of a systematic literature review and meta-analysis
      investigating the frequency and importance of different mechanisms by which
      climate has impacted natural populations. Most studies were from temperate
      latitudes of North America and Europe; almost half investigated bird populations.
      We found significantly greater support for indirect, biotic mechanisms than
      direct, abiotic mechanisms as mediators of the impact of climate on populations.
      In addition, biotic effects tended to have greater support than abiotic factors
      in studies of species from higher trophic levels. For primary consumers, the
      impact of climate was equally mediated by biotic and abiotic mechanisms, whereas
      for higher level consumers the mechanisms were most frequently biotic, such as
      predation or food availability. Biotic mechanisms were more frequently supported
      in studies that reported a directional trend in climate than in studies with no
      such climatic change, although sample sizes for this comparison were small. We
      call for more mechanistic studies of climate change impacts on populations,
      particularly in tropical systems.

PMID- 24677406
TI  - A novel semiautomatic parenchyma extraction method for improved MRI R2*
      relaxometry of iron loaded liver.
AB  - PURPOSE: To propose and evaluate an automatic method of extracting parenchyma
      from a manually delineated whole liver for the R2* measurement of iron load.
      MATERIALS AND METHODS: In all, 108 transfusion-dependent patients with a wide
      range of hepatic iron content were scanned with a multiecho gradient-echo
      sequence. The R2* was measured by fitting the average signal of liver parenchyma,
      extracted by the proposed semiautomatic parenchyma extraction (SAPE), traditional
      manually delineated multiple regions-of-interest (mROIs), and T2* thresholding
      methods to the noise-corrected monoexponential model. The R2* measurement
      accuracy of the SAPE method was evaluated through simulation; the intra- and
      interobserver reproducibility of SAPE, mROI, and T2* thresholding were assessed
      from the in vivo data using coefficient of variation (CoV). RESULTS: In the
      simulation, the mean absolute percentage error of R2* measurement using SAPE was
      0.23% (range 0.01%-1.09%). In vivo study, the CoVs of intra- and interobserver
      reproducibility were 0.83%, 1.39% for SAPE, 3.63%, 6.28% for mROI, and 1.62%,
      2.66% for T2* thresholding, respectively. CONCLUSION: The SAPE method provides an
      accurate and reliable approach to assessing the overall hepatic iron content. The
      improved magnetic resonance imaging (MRI) R2* reproducibility using the SAPE
      method may lead to more accurate tissue characterization and increased diagnostic
      confidence.

PMID- 24677407
TI  - Carbapenem-resistant Klebsiella pneumoniae colonization at liver transplantation:
      a management challenge.

PMID- 24677408
TI  - (31) P MR spectroscopic imaging of the human prostate at 7 T: T1 relaxation
      times, Nuclear Overhauser Effect, and spectral characterization.
AB  - PURPOSE: Optimization of phosphorus ((31) P) MR spectroscopic imaging (MRSI) of
      the human prostate at 7 T by the evaluation of T1 relaxation times and the
      Nuclear Overhauser Effect (NOE) of phosphorus-containing metabolites. METHODS:
      Twelve patients with prostate cancer and one healthy volunteer were scanned on a
      7 T whole-body system using a (31) P endorectal coil combined with an eight
      channel (1) H body array coil. T1 relaxation times were measured using
      progressive saturation in a two-dimensional localization sequence. (31) P MRSI
      was performed twice: once without NOE and once with NOE using low-power
      continuous wave (1) H irradiation to determine NOE enhancements. RESULTS: T1
      relaxation times of (31) P metabolites in the human prostate at 7 T varied
      between 3.0 and 8.3 s. Positive but variable NOE enhancements were measured for
      most metabolites. Remarkably, the (31) P MR spectra showed two peaks in chemical
      shift range of inorganic phosphate. CONCLUSION: Knowledge of T1 relaxation times
      and NOE enhancements enables protocol optimization for (31) P MRSI of the
      prostate at 7 T. With a strongly reduced (31) P flip angle (<= 45 degrees ), a
      (31) P MRSI dataset with optimal signal-to-noise ratio per unit time can be
      obtained within 15 minutes. The NOE enhancement can improve fitting accuracy, but
      its variability requires further investigation.

PMID- 24677409
TI  - Spindle epithelial tumor with thymus-like differentiation: A case report and
      comprehensive review of the literature and treatment options.
AB  - BACKGROUND: Spindle epithelial tumor with thymus-like differentiation (SETTLE) is
      a rare cancer of thymic origin with little information available for treating
      clinicians. METHODS: We performed a comprehensive literature search and updates
      were requested from all authors. We report one recent case. RESULTS: We present
      the most comprehensive review of the clinical literature for SETTLE. We
      identified 41 published cases. SETTLE usually presents as an asymptomatic neck
      mass. Most patients successfully underwent surgical resection of the primary
      tumor. The mean latency to develop metastasis was 10 years. SETTLE is uniformly
      responsive to radiotherapy and combination chemotherapy in the rare cases where
      response data are available. CONCLUSION: Although SETTLE is initially indolent,
      it has the capacity to metastasize late in its course. The malignant potential of
      this tumor might be underestimated because of the lack of long-term follow-up. In
      cases in which complete surgical resection is not possible, radiotherapy or
      combination chemotherapy is effective.

PMID- 24677411
TI  - Palladium enolate umpolung: cyclative diacetoxylation of alkynyl
      cyclohexadienones promoted by a Pd/SPRIX catalyst.
AB  - A novel palladium-catalyzed reaction involving an unusual nucleophilic attack on
      a palladium enolate was developed using a spiro-bis(isoxazoline) (SPRIX) ligand.
      Treatment of alkynyl cyclohexadienone substrates with a Pd/SPRIX catalyst in
      acetic acid under an oxygen atmosphere furnished diacetoxylated benzofuranone
      derivatives in good yields. This cyclative diacetoxylation proceeded
      enantioselectively in the presence of an optically pure SPRIX ligand. 

PMID- 24677410
TI  - Study of neuron survival on polypyrrole-embedded single-walled carbon nanotube
      substrates for long-term growth conditions.
AB  - Cultures of primary embryonic rat brain hippocampus neurons with supporting glia
      cells were carried out on different substrates containing polypyrrole (PPy)
      and/or single-walled carbon nanotubes (SWCNTs). Neuron adhesion, neurites and
      dendrites branching elongation, and development of neuron networks on substrates
      were followed by phase-contrast optical microscopy and quantified to state cell
      survival and proliferation. Suspensions of as-grown and purified SWCNTs were
      sprayed on a glass coverslips and PPy/SWCNTs were deposited by potentiodynamic
      electrochemical deposition. Cell neurotoxicity revealed by neuron death was very
      high for purified SWCNTs substrates in good agreement with [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) test showing lower
      viability on SWCNTs containing substrates compared with PPy-substrates and
      control samples probably due to the metal content and the carboxylic groups
      introduced during the purification. It is interesting to highlight that neurons
      grown on PPy-substrates adhere developing neurites and branching dendrites
      earlier even than on control cultures. On subsequent days the neurons are able to
      adapt to nanotube substrates developing neuron networks for 14-day cultures with
      similar patterns of complexity for control, PPy and PPy/SWCNT substrates.
      PPy/SWCNT substrates show a lower impedance value at frequencies under 1 Hz. We
      have come to the conclusion that glia cells and PPy added to the culture medium
      and substrates respectively, improve in some degree nanotube biocompatibility,
      cell adhesion and hence cell viability.

PMID- 24677412
TI  - Study on constant-step stress accelerated life tests in white organic light
      emitting diodes.
AB  - In order to obtain reliability information for a white organic light-emitting
      diode (OLED), two constant and one step stress tests were conducted with its
      working current increased. The Weibull function was applied to describe the OLED
      life distribution, and the maximum likelihood estimation (MLE) and its iterative
      flow chart were used to calculate shape and scale parameters. Furthermore, the
      accelerated life equation was determined using the least squares method, a
      Kolmogorov-Smirnov test was performed to assess if the white OLED life follows a
      Weibull distribution, and self-developed software was used to predict the average
      and the median lifetimes of the OLED. The numerical results indicate that white
      OLED life conforms to a Weibull distribution, and that the accelerated life
      equation completely satisfies the inverse power law. The estimated life of a
      white OLED may provide significant guidelines for its manufacturers and
      customers.

PMID- 24677413
TI  - Theoretical comparison, equivalent transformation, and conjunction operations of
      electromagnetic induction generator and triboelectric nanogenerator for
      harvesting mechanical energy.
AB  - Triboelectric nanogenerator (TENG) is a newly invented technology that is
      effective using conventional organic materials with functionalized surfaces for
      converting mechanical energy into electricity, which is light weight, cost
      effective and easy scalable. Here, we present the first systematic analysis and
      comparison of EMIG and TENG from their working mechanisms, governing equations
      and output characteristics, aiming at establishing complementary applications of
      the two technologies for harvesting various mechanical energies. The equivalent
      transformation and conjunction operations of the two power sources for the
      external circuit are also explored, which provide appropriate evidences that the
      TENG can be considered as a current source with a large internal resistance,
      while the EMIG is equivalent to a voltage source with a small internal
      resistance. The theoretical comparison and experimental validations presented in
      this paper establish the basis of using the TENG as a new energy technology that
      could be parallel or possibly equivalently important as the EMIG for general
      power application at large-scale. It opens a field of organic nanogenerator for
      chemists and materials scientists who can be first time using conventional
      organic materials for converting mechanical energy into electricity at a high
      efficiency. 

PMID- 24677414
TI  - The instrument 'sense of security in care--patients' evaluation': its development
      and presentation.
AB  - OBJECTIVE: The aim of this paper is to report the development, construction, and
      psychometric properties of the new instrument Sense of Security in Care -
      Patients' Evaluation (SEC-P) in palliative home care. METHODS: The preliminary
      instrument was based on a review of the literature and an analysis of qualitative
      interviews with patients about their sense of security. To test the instrument,
      161 patients (58% women) in palliative home care were recruited and participated
      in a structured interview based on a comprehensive questionnaire (response rate
      73%). We used principal component analysis to identify subscales and tested the
      construction in correlation with other scales and questions representing concepts
      that we expected to be related to sense of security in care. RESULTS: The
      principal component analysis resulted in three subscales: Care Interaction,
      Identity, and Mastery, built on a total of 15 items. The component solution had
      an explained variance of 55%. Internal consistency of the subscales ranged from
      0.84 to 0.69. Inter-scale correlations varied between 0.40 and 0.59. The scales
      were associated to varying degrees with the quality of the care process,
      perceived health, quality of life, stress, and general sense of security.
      CONCLUSIONS: The developed SEC-P provides a three-component assessment of
      palliative home care settings using valid and reliable scales. The scales were
      associated with other concepts in ways that were expected. The SEC-P is a
      manageable means of assessment that can be used to improve quality of care and in
      research focusing on patients' sense of security in care.

PMID- 24677415
TI  - Spin-state ordering on one sub-lattice of a mononuclear iron(III) spin crossover
      complex exhibiting LIESST and TIESST.
AB  - The two-step spin crossover in mononuclear iron(III) complex [Fe(salpm)2 ]ClO4
      ?0.5 EtOH (1) is shown to be accompanied by a structural phase transition as
      concluded from (57) Fe Mossbauer spectroscopy and single crystal X-ray
      diffraction, with spin-state ordering on just one of two sub-lattices in the
      intermediate magnetic and structural phase. The complex also exhibits thermal-
      and light-induced spin-state trapping (TIESST and LIESST), and relaxation from
      the LIESST and TIESST excited states occurs via the broken symmetry intermediate
      phase. Two relaxation events are evident in both experiments, that is, two
      T(LIESST) and two T(TIESST) values are recorded. The change in symmetry which
      accompanies the TIESST effect was followed in real time using single crystal
      diffraction. After flash freezing at 15 K the crystal was warmed to 40 K at which
      temperature superstructure reflections were observed to appear and disappear
      within a 10 000 s time range. In the frame of the international year of
      crystallography, these results illustrate how X-ray diffraction makes it possible
      to understand complex ordering phenomena. 

PMID- 24677416
TI  - Exploring single semiconductor nanowires with a multimodal hard X-ray nanoprobe.
AB  - Semiconductor nanowires offer new opportunities for optoelectronic and spintronic
      nanodevices. However, their full potential is ultimately dictated by our ability
      to control multiple property-function relationships taking place at the nanoscale
      in the spatial and time domains. Only a combination of high-resolution analytical
      techniques can provide a comprehensive understanding of their complex
      functionalities. Here we describe how a multimodal hard X-ray nanoprobe addresses
      fundamental questions in nanowire research. Selected topics ranging from cluster
      formation, dopant segregation, and phase separations to quantum confinement
      effects are investigated with sub-100 nm spatial resolution and sub-50 ps
      temporal resolution. This approach opens new avenues for structural, composition
      and optical studies with broad applicability in materials science. 

PMID- 24677417
TI  - A large conditioned pain modulation response is not related to a large blood
      pressure response: a study in healthy men.
AB  - BACKGROUND: Endogenous pain modulation has been studied with the conditioned pain
      modulation (CPM) paradigm with large differences in the magnitude of the CPM
      effect. We hypothesized that differences in CPM effects might be associated with
      differences in blood pressure responses to the conditioning stimulus when
      comparing the CPM effects using two different conditioning stimuli. METHODS: A
      single-blind repeated-measures design with block-randomization was applied on 25
      healthy male subjects. The test stimulus (TS; tonic heat pain for 120 s) was
      first presented alone, thereafter in parallel with a conditioning stimulus (CS).
      Conditioning stimuli were either a cold pressor test (CPT) or equally painful
      ischaemic muscle pain (ISC), both lasting 120 s. Finger blood pressure and heart
      rate were recorded continuously. Data were analysed in a linear mixed model
      framework with CS type (CPT or ISC) and conditioning (TS or TS + CS) as
      independent factors. RESULTS: An inhibitory CPM effect was found for both types
      of conditioning (p < 0.001). The CPM effect was larger during CPT conditioning
      compared with ISC conditioning (p = 0.001). No association with the concomitant
      cardiovascular response (blood pressure and heart rate) was found (p > 0.34).
      CONCLUSION: Cold pressor pain CS induces larger CPM effects than ischaemic pain
      CS. The larger CPM effect is, however, not associated with a larger blood
      pressure response. Other factors related to the CS should be investigated to
      understand why different CS modalities give different CPM effects.

PMID- 24677418
TI  - Surface-junction effects on interfacial electron transfer between
      bis(terpyridine)iron(II) and hydrogen-terminated silicon(111) electrode.
AB  - Interfacial electron transfer at bis(tpy)-iron(II) complexes (tpy=2,2':6',2''
      terpyridine) on Si(111) electrodes was investigated by using four types of
      surfaceanchor terpyridine ligands. Despite the greater distance, electron
      transfer between the bis(tpy)-iron(II) unit and the electrode is accelerated in
      surface-anchor ligands with an additional phenylene group.

PMID- 24677419
TI  - Charge trapping at the step edges of TiO(2) anatase (101).
AB  - A combination of photoemission, atomic force, and scanning tunneling
      microscopy/spectroscopy measurements shows that excess electrons in the TiO2
      anatase (101) surface are trapped at step edges. Consequently, steps act as
      preferred adsorption sites for O2 . In density functional theory calculations
      electrons localize at clean step edges, this tendency is enhanced by O vacancies
      and hydroxylation. The results show the importance of defects for the wide
      ranging applications of titania. 

PMID- 24677420
TI  - Comparison of magnetic resonance feature tracking for systolic and diastolic
      strain and strain rate calculation with spatial modulation of magnetization
      imaging analysis.
AB  - PURPOSE: To compare cardiovascular magnetic resonance-feature tracking (CMR-FT)
      with spatial modulation of magnetization (SPAMM) tagged imaging for the
      calculation of short and long axis Lagrangian strain measures in systole and
      diastole. MATERIALS AND METHODS: Healthy controls (n = 35) and patients with
      dilated cardiomyopathy (n = 10) were identified prospectively and underwent
      steady-state free precession (SSFP) cine imaging and SPAMM imaging using a
      gradient-echo sequence. A timed offline analysis of images acquired at identical
      horizontal long and short axis slice positions was performed using CMR-FT and
      dynamic tissue-tagging (CIMTag2D). Agreement between strain and strain rate (SR)
      values calculated using these two different methods was assessed using the Bland
      Altman technique. RESULTS: Across all participants, there was good agreement
      between CMR-FT and CIMTag for calculation of peak systolic global circumferential
      strain (-22.7 +/- 6.2% vs. -22.5 +/- 6.9%, bias 0.2 +/- 4.0%) and SR (-1.35 +/-
      0.42 1/s vs. -1.22 +/- 0.42 1/s, bias 0.13 +/- 0.33 1/s) and early diastolic
      global circumferential SR (1.21 +/- 0.44 1/s vs. 1.07 +/- 0.30 1/s, bias -0.14 +/
      0.34 1/s) at the subendocardium. There was satisfactory agreement for derivation
      of peak systolic global longitudinal strain (-18.1 +/- 5.0% vs. -16.7 +/- 4.8%,
      bias 1.3 +/- 3.8%) and SR (-1.04 +/- 0.29 1/s vs. -0.95 +/- 0.32 1/s, bias 0.09
      +/- 0.26 1/s). The weakest agreement was for early diastolic global longitudinal
      SR (1.10 +/- 0.40 1/s vs. 0.67 +/- 0.32 1/s, bias -0.42 +/- 0.40 1/s), although
      the correlation remained significant (r = 0.42, P < 0.01). CMR-FT generated these
      data over four times quicker than CIMTag. CONCLUSION: There is sufficient
      agreement between systolic and diastolic strain measures calculated using CMR-FT
      and myocardial tagging for CMR-FT to be considered as a potentially feasible and
      rapid alternative.

PMID- 24677422
TI  - Cetacean range and climate in the eastern North Atlantic: future predictions and
      implications for conservation.
AB  - There is increasing evidence that the distributions of a large number of species
      are shifting with global climate change as they track changing surface
      temperatures that define their thermal niche. Modelling efforts to predict
      species distributions under future climates have increased with concern about the
      overall impact of these distribution shifts on species ecology, and especially
      where barriers to dispersal exist. Here we apply a bio-climatic envelope
      modelling technique to investigate the impacts of climate change on the
      geographic range of ten cetacean species in the eastern North Atlantic and to
      assess how such modelling can be used to inform conservation and management. The
      modelling process integrates elements of a species' habitat and thermal niche,
      and employs "hindcasting" of historical distribution changes in order to verify
      the accuracy of the modelled relationship between temperature and species range.
      If this ability is not verified, there is a risk that inappropriate or inaccurate
      models will be used to make future predictions of species distributions. Of the
      ten species investigated, we found that while the models for nine could
      successfully explain current spatial distribution, only four had a good ability
      to predict distribution changes over time in response to changes in water
      temperature. Applied to future climate scenarios, the four species-specific
      models with good predictive abilities indicated range expansion in one species
      and range contraction in three others, including the potential loss of up to 80%
      of suitable white-beaked dolphin habitat. Model predictions allow identification
      of affected areas and the likely time-scales over which impacts will occur. Thus,
      this work provides important information on both our ability to predict how
      individual species will respond to future climate change and the applicability of
      predictive distribution models as a tool to help construct viable conservation
      and management strategies. 

PMID- 24677421
TI  - Completing the structural family portrait of the human EphB tyrosine kinase
      domains.
AB  - The EphB receptors have key roles in cell morphology, adhesion, migration and
      invasion, and their aberrant action has been linked with the development and
      progression of many different tumor types. Their conflicting expression patterns
      in cancer tissues, combined with their high sequence and structural identity,
      present interesting challenges to those seeking to develop selective therapeutic
      molecules targeting this large receptor family. Here, we present the first
      structure of the EphB1 tyrosine kinase domain determined by X-ray crystallography
      to 2.5A. Our comparative crystalisation analysis of the human EphB family kinases
      has also yielded new crystal forms of the human EphB2 and EphB4 catalytic
      domains. Unable to crystallize the wild-type EphB3 kinase domain, we used
      rational engineering (based on our new structures of EphB1, EphB2, and EphB4) to
      identify a single point mutation which facilitated its crystallization and
      structure determination to 2.2 A. This mutation also improved the soluble
      recombinant yield of this kinase within Escherichia coli, and increased both its
      intrinsic stability and catalytic turnover, without affecting its ligand-binding
      profile. The partial ordering of the activation loop in the EphB3 structure
      alludes to a potential cis-phosphorylation mechanism for the EphB kinases. With
      the kinase domain structures of all four catalytically competent human EphB
      receptors now determined, a picture begins to emerge of possible opportunities to
      produce EphB isozyme-selective kinase inhibitors for mechanistic studies and
      therapeutic applications. 

PMID- 24677423
TI  - Drug delivery with PEGylated MoS2 nano-sheets for combined photothermal and
      chemotherapy of cancer.
AB  - MoS2 nanosheets functionalized with poly-ethylene glycol are for the first time
      used as a multifunctional drug delivery system with high drug loading capacities.
      Using doxorubicin as the model drug and taking advantages of the strong near
      infrared absorbance of MoS2, combined photothermal and chemotherapy of cancer is
      realized in animal experiments, achieving excellent synergistic anti-tumor effect
      upon systemic administration.

PMID- 24677425
TI  - Lessons learned from excess mortality associated with Klebsiella pneumoniae
      carbapenemase 2-producing K. pneumoniae in liver transplant recipients.

PMID- 24677426
TI  - Organic-inorganic interface-induced multi-fluorescence of MgO nanocrystal
      clusters and their applications in cellular imaging.
AB  - Surface functionalization of inorganic nanomaterials through chemical binding of
      organic ligands on the surface unsaturated atoms, forming unique organic
      inorganic interfaces, is a powerful approach for creating special functions for
      inorganic nanomaterials. Herein, we report the synthesis of hierarchical MgO
      nanocrystal clusters (NCs) with an organic-inorganic interface induced multi
      fluorescence and their application as new alternative labels for cellular
      imaging. The synthetic method was established by a dissolution and regrowth
      process with the assistance of carboxylic acid, in which the as-prepared MgO NCs
      were modified with carboxylic groups at the coordinatively unsaturated atoms of
      the surface. By introducing acetic acid to partially replace oleic acid in the
      reaction, the optical absorption of the produced MgO NCs was progressively
      engineered from the UV to the visible region. Importantly, with wider and
      continuous absorption profile, those MgO NCs presented bright and tunable
      multicolor emissions from blue-violet to green and yellow, with the highest
      absolute quantum yield up to (33+/-1) %. The overlap for the energy levels of the
      inorganic-organic interface and low-coordinated states stimulated a unique
      fluorescence resonance energy transfer phenomenon. Considering the potential
      application in cellular imaging, such multi-fluorescent MgO NCs were further
      encapsulated with a silica shell to improve the water solubility and stability.
      As expected, the as-formed MgO@SiO2 NCs possessed great biocompatibility and high
      performance in cellular imaging. 

PMID- 24677424
TI  - Biofragments: an approach towards predicting protein function using biologically
      related fragments and its application to Mycobacterium tuberculosis CYP126.
AB  - We present a novel fragment-based approach that tackles some of the challenges
      for chemical biology of predicting protein function. The general approach, which
      we have termed biofragments, comprises two key stages. First, a biologically
      relevant fragment library (biofragment library) can be designed and constructed
      from known sets of substrate-like ligands for a protein class of interest.
      Second, the library can be screened for binding to a novel putative ligand
      binding protein from the same or similar class, and the characterization of hits
      provides insight into the basis of ligand recognition, selectivity, and function
      at the substrate level. As a proof-of-concept, we applied the biofragments
      approach to the functionally uncharacterized Mycobacterium tuberculosis (Mtb)
      cytochrome P450 isoform, CYP126. This led to the development of a tailored CYP
      biofragment library with notable 3D characteristics and a significantly higher
      screening hit rate (14%) than standard drug-like fragment libraries screened
      previously against Mtb CYP121 and 125 (4% and 1%, respectively). Biofragment hits
      were identified that make both substrate-like type-I and inhibitor-like type-II
      interactions with CYP126. A chemical-fingerprint-based substrate model was built
      from the hits and used to search a virtual TB metabolome, which led to the
      discovery that CYP126 has a strong preference for the recognition of aromatics
      and substrate-like type-I binding of chlorophenol moieties within the active site
      near the heme. Future catalytic analyses will be focused on assessing CYP126 for
      potential substrate oxidative dehalogenation.

PMID- 24677427
TI  - Biocompatibility evaluation of porous ceria foams for orthopedic tissue
      engineering.
AB  - Ceria ceramics have the unique ability to protect cells from free radical-induced
      damage, making them materials of interest for biomedical applications. To expand
      upon the understanding of the potential of ceria as a biomaterial, porous ceria,
      fabricated via direct foaming, was investigated to assess its biocompatibility
      and its ability to scavenge free radicals. A mouse osteoblast (7F2) cell line was
      cultured with the ceria foams to determine the extent of the foams' toxicity.
      Toxicity assessments indicate that mouse osteoblasts cultured directly on the
      ceria scaffold for 72 h did not show a significant (p > 0.05) increase in
      toxicity, but rather show comparable toxicity to cells cultured on porous 45S5
      Bioglass. The in vitro inflammatory response elicited from porous ceria foams was
      measured as a function of tumor necrosis factor alpha (TNF-alpha) secreted from a
      human monocytic leukemia cell line. Results indicate that the ceria foams do not
      cause a significant inflammatory response, eliciting a response of 27.1 +/- 7.1
      pg mL(-1) of TNF-alpha compared to 36.3 +/- 5.8 pg mL(-1) from cells on Bioglass,
      and 20.1 +/- 2.9 pg mL(-1) from untreated cells. Finally, we report cellular
      toxicity in response to free radicals from tert-butyl hydroperoxide with and
      without foamed ceria. Our preliminary results show that the foamed ceria is able
      to decrease the toxic effect of induced oxidative stress. Collectively, this
      study demonstrates that foamed ceria scaffolds do not activate an inflammatory
      response, and show potential free radical scavenging ability, thus they have
      promise as an orthopedic biomaterial.

PMID- 24677428
TI  - The influence of biodegradable magnesium alloys on the osteogenic differentiation
      of human mesenchymal stem cells.
AB  - The postdegradation effect of pure Mg, Mg-1Y, Mg-5Al, and Mg-2Ca alloys on the
      differentiation, proliferation and gene expression of human mesenchymal stem
      cells (hMSCs) was investigated. It was revealed that that Mg(2+) ions result in
      an increase in cell proliferation. However, we observed a maximum concentration
      (approximately 8.0 * 10(-4) M) that was favourable to ATP production, above which
      ATP production began to decrease. In contrast to proliferation, no maximum
      concentration for osteogenic differentiation was observed, with increasing
      concentration of Mg(2+) ions resulting in an increase in osteogenic
      differentiation across the entire tested range. Interestingly, the Mg-2Ca alloy
      had minimal effect on osteogenic differentiation, with Mg-1Y and pure Mg having a
      superior effect on the proliferation and differentiation of hMSCs. This was also
      observed from gene expression data, where these alloys upregulated TGFbeta-1,
      SMAD4, FGF-2, FGF-10, and BMP-2, while SOX-2, SOX-9, and TNF-alpha were
      downregulated. Increased expression of TGFbeta-1, SMAD4, BMPs, and COLIA1 protein
      provided further evidence to support osteogenic differentiation and that the
      influence of the alloying extracts on differentiation may be via the SMAD
      signaling pathway.

PMID- 24677429
TI  - Cortical dopamine release during a behavioral response inhibition task.
AB  - Dopamine (DA) dysregulation within fronto-striatal circuitry may underlie
      impulsivity in alcohol and other substance use disorders. To date, no one has
      directly demonstrated DA release during a task requiring the control of impulsive
      behavior. The current study was conducted to determine whether a response
      inhibition task (stop signal task; SST) would elicit detectable extrastriatal DA
      release in healthy controls. We hypothesized that DA release would be detected in
      regions previously implicated in different aspects of inhibitory control. [(18)
      F]Fallypride (FAL) PET imaging was performed in nine healthy males (24.6 +/- 4.1
      y.o.) to assess changes in cortical DA during a SST relative to a baseline "Go"
      task. On separate days, subjects received one FAL scan during the SST, and one
      FAL scan during a "Go" control; task-order was counter-balanced across subjects.
      Parametric BPND images were generated and analyzed with SPM8. Voxel-wise analysis
      indicated significant SST-induced DA release in several cortical regions involved
      in inhibitory control, including the insula, cingulate cortex, orbitofrontal
      cortex, precuneus, and supplementary motor area. There was a significant positive
      correlation between stop signal reaction time and DA release in the left
      orbitofrontal cortex, right middle frontal gyrus, and right precentral gyrus.
      These data support the feasibility of using FAL PET to study DA release during
      response inhibition, enabling investigation of relationships between DA function
      and impulsive behavior.

PMID- 24677431
TI  - The malleable effect of name fluency on pharmaceutical drug perception.
AB  - Based on the fluency theory, a recent study by Dohle and Siegrist revealed that
      complex pharmaceutical drug names are perceived as more hazardous than simple
      drug names and thus negatively influence patients' willingness to buy. This study
      explored the malleability of the name fluency effect on pharmaceutical drug
      perception by examining the fluency effect in the domain of risk versus
      advancedness judgment. The findings indicated that depending on how the fluency
      feeling is interpreted in the context of initial judgment task (e.g. advancedness
      vs risk), disfluent drug names can positively influence a patient's perception of
      the drug, reversing the typical fluency effect. 

PMID- 24677430
TI  - Risk of congenital heart disease in relatives of probands with conotruncal
      cardiac defects: an evaluation of 1,620 families.
AB  - Current recurrence risk counseling for conotruncal cardiac defects (CTD) is based
      on empiric estimates from multiple studies. We examined the risk of congenital
      heart disease (CHD) in relatives of probands with CTDs to assist in counseling
      practices in the current era. One thousand six-twenty probands with CTDs and no
      reported chromosomal or genetic abnormalities were recruited sequentially. A
      three-generation pedigree was obtained for each proband by a genetic counselor
      detailing the presence and type of CHD in each family member. Risks and 95%
      confidence intervals (CI) were calculated for sub-groups of relatives based on
      degree of relationship for all probands and by individual lesion of the proband.
      For pairs of affected relatives, concordance rates were calculated. Severity of
      CHD in the affected relative was assessed. The risk of CHD was higher in siblings
      (4.4%, 95% CI 3.4-5.4) than in parents (1.5%, 95% CI 1.1-1.9). Risk varied by the
      cardiac lesion of the proband with the highest risk in first-degree relatives of
      probands with tetralogy of Fallot and the lowest in D-transposition of the great
      arteries. 39% of affected parents and 69% of affected siblings had a concordant
      lesion (i.e., CTD). Most affected siblings of probands with severe CTDs had
      complex defects (58%), whereas very few affected parents had complex defects
      (20%). These data suggest that recurrence risk varies by lesion and relationship,
      with substantial concordance observed by cardiac lesion and complexity of
      disease, particularly among siblings. These findings contribute to risk
      counseling in the current era.

PMID- 24677432
TI  - Hope and fatigue in chronic illness: The role of perceived stress.
AB  - Fatigue is a debilitating symptom of chronic illness that is deleteriously
      affected by perceived stress, a process particularly relevant to inflammatory
      disease. Hopefulness, a goal-based motivational construct, may beneficially
      influence stress and fatigue, yet little research has examined these
      associations. We assessed the relation between hope and fatigue, and the
      mediating effect of stress, in individuals with fibromyalgia, arthritis, and
      inflammatory bowel disease. Covarying age, sex, and pain, stress partially
      mediated the association between hope and fatigue; those with greater hope
      reported less stress and consequent fatigue. Therapeutically, bolstering hope may
      allow proactive management of stressors, resulting in less fatigue. 

PMID- 24677433
TI  - Reversed hierarchy in the brain for general and specific cognitive abilities: a
      morphometric analysis.
AB  - Intelligence is composed of a set of cognitive abilities hierarchically
      organized. General and specific abilities capture distinguishable, but related,
      facets of the intelligence construct. Here, we analyze gray matter with three
      morphometric indices (volume, cortical surface area, and cortical thickness) at
      three levels of the intelligence hierarchy (tests, first-order factors, and a
      higher-order general factor, g). A group of one hundred and four healthy young
      adults completed a cognitive battery and underwent high-resolution structural
      MRI. Latent scores were computed for the intelligence factors and tests were also
      analyzed. The key finding reveals substantial variability in gray matter
      correlates at the test level, which is substantially reduced for the first-order
      and the higher-order factors. This supports a reversed hierarchy in the brain
      with respect to cognitive abilities at different psychometric levels: the greater
      the generality, the smaller the number of relevant gray matter clusters
      accounting for individual differences in intelligent performance.

PMID- 24677435
TI  - Aryl formate as bifunctional reagent: applications in palladium-catalyzed
      carbonylative coupling reactions using in situ generated CO.
AB  - After decades of development, carbonylation reactions have become one of the most
      powerful tools in modern organic synthesis. However, the requirement of CO gas
      limits the applications of such reactions. Reported herein is a versatile and
      practical protocol for carbonylative reactions which rely on the cooperation of
      phenyl formate and nonaflate, and the generation of CO in situ. This protocol has
      a high functionalgroup tolerance and could be applied in carbonylations with C,
      N, and, O nucleophiles. The corresponding amides, alkynones, furanones, and aryl
      benzoates were synthesized in good yields.

PMID- 24677436
TI  - 1-Alkenylcalcium iodide: synthesis and stability.
AB  - To enhance the scope of heavy calcium-based Grignard reagents, 1,2-dihydro-4
      iodonaphthalene (1) was reduced with calcium in THF giving tetrakis(thf) (1,2
      dihydronaphth-4-yl)calcium iodide (2). This derivative represents a 1
      alkenylcalcium complex based on X-ray structure determination and NMR data. The
      stability of this compound is significantly reduced compared with the aromatic
      naphthylcalcium iodide. 

PMID- 24677437
TI  - Effects of mindfulness and distraction on pain depend upon individual differences
      in pain catastrophizing: an experimental study.
AB  - BACKGROUND: The aim of this study was to investigate whether the perception of
      experimental pain was different during a mindfulness manipulation than during a
      distraction manipulation. Furthermore, it was examined if effects were moderated
      by dispositional pain catastrophizing. METHODS: Undergraduate students (n = 51)
      completed self-report measures of pain catastrophizing and mindfulness.
      Subsequently, they were administered a series of mildly painful heat stimuli,
      which they had to rate. During pain induction, participants listened to either a
      pre-recorded mindfulness instruction (mindfulness group) or a pre-recorded story
      (distraction group). RESULTS: After controlling for baseline experimental pain
      ratings, we found no overall group effect, indicating that there was no
      difference in experienced pain between the mindfulness group and the distraction
      group. However, a significant moderation effect was found. When dispositional
      pain catastrophizing was high, pain was less pronounced in the mindfulness group
      than in the distraction group, whereas the opposite effect was found when the
      level of pain catastrophizing was low. CONCLUSIONS: The findings suggest that in
      persons with a high level of catastrophic thinking about pain, mindfulness-based
      coping may be a better approach than distraction.

PMID- 24677438
TI  - Transition from pi radicals to sigma radicals: substituent-tuned cyclization of
      hydrazonyl radicals.
AB  - Hydrazonyl radicals are known for their p-electronic structures; however, their s
      electronic structures have not been reported as yet. Herein, we show that readily
      accessible b,g- and g,d-unsaturated N-trichloroacetyl and Ntrifluoroacetyl
      hydrazones can be conveniently converted into hydrazonyl s radicals, which
      subsequently undergo 5-exo-trig radical cyclization at the N1 or N2 atom to form
      pyrazolines and azomethine imines, respectively.

PMID- 24677439
TI  - Quantification of nano- and mesoscale phase separation and relation to donor and
      acceptor quantum efficiency, J(sc), and FF in polymer:fullerene solar cells.

PMID- 24677441
TI  - Missing effects of anthropogenic nutrient deposition on sentinel alpine
      ecosystems.
AB  - Anthropogenic nitrogen (N) deposition affects unproductive remote alpine and
      circumpolar ecosystems, which are often considered sentinels of global change.
      Human activities and forest fires can also elevate phosphorus (P) deposition,
      possibly compounding the ecological effects of increased N deposition given the
      ubiquity of nutrient co-limitation of primary producers. Low N : P ratios coupled
      with evidence of NP-limitation from bioassays led us to hypothesize that P
      indirectly stimulates phytoplankton by amplifying the direct positive effect of N
      (i.e. serial N-limitation) in alpine ponds. We tested the hypothesis using the
      first replicated N * P enrichment experiment conducted at the whole-ecosystem
      level, which involved 12 alpine ponds located in the low N deposition backcountry
      of the eastern Front Range of the Canadian Rockies. Although applications of N
      and P elevated ambient N and P concentrations by 2-5*, seston and plankton
      remained relatively unaffected in the amended ponds. However, additions of
      ammonium nitrate elevated the delta(15) N signals of both primary producers and
      herbivores (fairy shrimp; Anostraca), attesting to trophic transfer of N
      deposition to consumers. Further, in situ bioassays revealed that grazing by high
      ambient densities of fairy shrimp together with potential competition from algae
      lining the pond bottoms suppressed the otherwise serially N-limited response by
      phytoplankton. Our findings highlight how indirect effects of biotic interactions
      rather the often implicit direct effects of chemical changes can regulate the
      sensitivities of extreme ecosystems to nutrient deposition.

PMID- 24677440
TI  - The development of antimicrobial a-AApeptides that suppress proinflammatory
      immune responses.
AB  - Herein we describe the development of a new class of antimicrobial and anti
      inflammatory peptidomimetics: cyclic lipo-alpha-AApeptides. They have potent and
      broad-spectrum antibacterial activity against a range of clinically relevant
      pathogens, including both multidrug-resistant Gram-positive and Gram-negative
      bacteria. Fluorescence microscopy suggests that cyclic lipo-alpha-AApeptides kill
      bacteria by disrupting bacterial membranes, possibly through a mechanism similar
      to that of cationic host-defense peptides (HDPs). Furthermore, the cyclic lipo
      alpha-AApeptide can mimic cationic host-defense peptides by antagonizing Toll
      like receptor 4 (TLR4) signaling responses and suppressing proinflammatory
      cytokines such as tumor necrosis factor-alpha (TNF-alpha). Our results suggest
      that by mimicking HDPs, cyclic lipo-alpha-AApeptides could emerge as a new class
      of antibiotic agents that directly kill bacteria, as well as novel
      antiinflammatory agents that act through immunomodulation.

PMID- 24677434
TI  - A review of organic and inorganic biomaterials for neural interfaces.
AB  - Recent advances in nanotechnology have generated wide interest in applying
      nanomaterials for neural prostheses. An ideal neural interface should create
      seamless integration into the nervous system and performs reliably for long
      periods of time. As a result, many nanoscale materials not originally developed
      for neural interfaces become attractive candidates to detect neural signals and
      stimulate neurons. In this comprehensive review, an overview of state-of-the-art
      microelectrode technologies provided fi rst, with focus on the material
      properties of these microdevices. The advancements in electro active
      nanomaterials are then reviewed, including conducting polymers, carbon nanotubes,
      graphene, silicon nanowires, and hybrid organic-inorganic nanomaterials, for
      neural recording, stimulation, and growth. Finally, technical and scientific
      challenges are discussed regarding biocompatibility, mechanical mismatch, and
      electrical properties faced by these nanomaterials for the development of long
      lasting functional neural interfaces.

PMID- 24677442
TI  - Effect of induction chemotherapy on swallow physiology and saliva production in
      patients with head and neck cancer: a pilot study.
AB  - BACKGROUND: No objective data are available to assess the potential damage
      induction chemotherapy alone contributes to swallowing physiology and salivary
      production in patients with locally and regionally confined head and neck cancer.
      METHODS: Thirteen patients with head and neck cancer were evaluated preinduction
      and postinduction chemotherapy. Assessment included: (1) percentage of nutrition
      taken orally and food consistencies in diet; (2) videofluorographic swallow
      evaluation; (3) whole mouth saliva collection; (4) quality-of-life questionnaire;
      and (5) pain and oral mucositis scores. RESULTS: All patients were able to
      consume most foods and took 100% of their nutrition orally both preinduction and
      postinduction chemotherapy. Although a number of swallow measures worsened, no
      statistically significant differences were observed in diet, quality of life
      measures, pain, or saliva weight, or in most temporal swallow measures.
      Pharyngeal residue decreased significantly after chemotherapy. CONCLUSION:
      Induction chemotherapy alone did not significantly negatively alter swallowing
      physiology and salivary secretion, although the trend was toward worsening in
      function.

PMID- 24677444
TI  - Alternating current electrohydrodynamics induced nanoshearing and fluid
      micromixing for specific capture of cancer cells.
AB  - We report a new tuneable alternating current (ac) electrohydrodynamics (ac-EHD)
      force referred to as "nanoshearing" which involves fluid flow generated within a
      few nanometers of an electrode surface. This force can be externally tuned via
      manipulating the applied ac-EHD field strength. The ability to manipulate ac-EHD
      induced forces and concomitant fluid micromixing can enhance fluid transport
      within the capture domain of the channel (e.g., transport of analytes and hence
      increase target-sensor interactions). This also provides a new capability to
      preferentially select strongly bound analytes over nonspecifically bound cells
      and molecules. To demonstrate the utility and versatility of nanoshearing
      phenomenon to specifically capture cancer cells, we present proof-of-concept data
      in lysed blood using two microfluidic devices containing a long array of
      asymmetric planar electrode pairs. Under the optimal experimental conditions, we
      achieved high capture efficiency (e.g., approximately 90%; %RSD=2, n=3) with a 10
      fold reduction in nonspecific adsorption of non-target cells for the detection of
      whole cells expressing Human Epidermal Growth Factor Receptor 2 (HER2). We
      believe that our ac-EHD devices and the use of tuneable nanoshearing phenomenon
      may find relevance in a wide variety of biological and medical applications.

PMID- 24677443
TI  - The minus-end actin capping protein, UNC-94/tropomodulin, regulates development
      of the Caenorhabditis elegans intestine.
AB  - BACKGROUND: Tropomodulins are actin-capping proteins that regulate the stability
      of the slow-growing, minus-ends of actin filaments. The C. elegans tropomodulin
      homolog, UNC-94, has sequence and functional similarity to vertebrate
      tropomodulins. We investigated the role of UNC-94 in C. elegans intestinal
      morphogenesis. RESULTS: In the embryonic C. elegans intestine, UNC-94 localizes
      to the terminal web, an actin- and intermediate filament-rich structure that
      underlies the apical membrane. Loss of UNC-94 function results in areas of
      flattened intestinal lumen. In worms homozygous for the strong loss-of-function
      allele, unc-94(tm724), the terminal web is thinner and the amount of F-actin is
      reduced, pointing to a role for UNC-94 in regulating the structure of the
      terminal web. The non-muscle myosin, NMY-1, also localizes to the terminal web,
      and we present evidence that increasing actomyosin contractility by depleting the
      myosin phosphatase regulatory subunit, mel-11, can rescue the flattened lumen
      phenotype of unc-94 mutants. CONCLUSIONS: The data support a model in which minus
      end actin capping by UNC-94 promotes proper F-actin structure and contraction in
      the terminal web, yielding proper shape of the intestinal lumen. This establishes
      a new role for a tropomodulin in regulating lumen shape during tubulogenesis.

PMID- 24677445
TI  - Impact of donor warm ischemia time on outcomes after donation after cardiac death
      liver transplantation.

PMID- 24677447
TI  - Liver lesion conspicuity during real-time MR-guided radiofrequency applicator
      placement using spoiled gradient echo and balanced steady-state free precession
      imaging.
AB  - PURPOSE: To retrospectively evaluate the conspicuity of liver lesions in a
      fluoroscopic spoiled gradient echo (GRE) and a balanced steady-state free
      precession (SSFP) magnetic resonance imaging (MRI) sequence. MATERIALS AND
      METHODS: In all, 103 patients with hepatocellular carcinomas (HCC) (41) or liver
      metastases (67) were treated using MR-guided radiofrequency ablation in a wide
      bore 1.5 T scanner. A multislice real-time spoiled GRE sequence allowing for a T1
      weighting (T1W) and a balanced SSFP sequence allowing for a T2/T1W contrast were
      used for MR guidance. The contrast-to-noise-ratio (CNR) of the lesions was
      calculated and lesion conspicuity was assessed retrospectively (easily detectable
      / difficult to detect / not detectable). RESULTS: HCC was easily detectable in
      33/52% (GRE/SSFP), difficult to detect in 30/18%, and not detectable in 37/30% of
      the cases. Mean CNR varied widely (9.1 for GRE vs. 16.4 for SSFP). Liver
      metastases were easily detectable in 58/41% (GRE/SSFP), difficult to detect in
      14/21%, and not detectable in 28/38% of the cases. Mean CNR for liver metastases
      was 11.5 (GRE) vs. 12.7 (SSFP). Twenty percent of all lesions could not be
      detected with either of the MR fluoroscopy sequences. CONCLUSION: MR fluoroscopy
      using GRE and SSFP contrast enabled real-time detectability of 80% of the liver
      lesions.

PMID- 24677448
TI  - Bone tissue engineering and regenerative medicine: targeting pathological
      fractures.
AB  - Patients with bone diseases have the highest risk of sustaining fractures and of
      suffering from nonunion bone healing due to tissue degeneration. Current fracture
      management strategies are limited in design and functionality and do not
      effectively promote bone healing within a diseased bone environment. Fracture
      management approaches include pharmaceutical therapy, surgical intervention, and
      tissue regeneration for fracture prevention, fracture stabilization, and fracture
      site regeneration, respectively. However, these strategies fail to accommodate
      the pathological nature of fragility fractures, leading to unwanted side effects,
      implant failures, and nonunions. To target fragility fractures, fracture
      management strategies should include bioactive bone substitutes designed for the
      pathological environment. However, the clinical outcome of these materials must
      be predictable within various disease environments. Initial development of a
      targeted treatment strategy should focus on simulating the physiological in vitro
      bone environment to predict clinical effectiveness of the engineered bone. An in
      vitro test system can facilitate reduction of implant failures and non-unions in
      fragility fractures.

PMID- 24677446
TI  - Structure and function of LGR5: an enigmatic G-protein coupled receptor marking
      stem cells.
AB  - G-protein coupled receptors (GPCRs) are an important class of membrane protein
      that transmit extracellular signals invoked by sensing molecules such as hormones
      and neurotransmitters. GPCR dysfunction is implicated in many diseases and hence
      these proteins are of great interest to academia and the pharmaceutical industry.
      Leucine-rich repeat-containing GPCRs contain a characteristic extracellular
      domain that is an important modulator of intracellular signaling. One member of
      this class is the leucine-rich repeat-containing G-protein-coupled receptor 5
      (LGR5), a stem cell marker in intestinal crypts, and mammary glands. LGR5
      modulates Wnt signaling in the presence of the ligand R-spondin (RSPO). The
      mechanism of activation of LGR5 by RSPO is not understood, nor is the
      intracellular signaling mechanism known. Recently reported structures of the
      extracellular domain of LGR5 bound to RSPO reveal a horseshoe-shaped architecture
      made up of consecutive leucine-rich repeats, with RSPO bound on the concave
      surface. This review discusses the discovery of LGR5 and the impact it is having
      on our understanding of stem cell and cancer biology of the colon. In addition,
      it covers functional relationships suggested by sequence homology and structural
      analyses, as well as some intriguing conundrums with respect to the involvement
      of LGR5 in Wnt signaling. 

PMID- 24677449
TI  - Different pools of postsynaptic GABAA receptors mediate inhibition evoked by low-
      and high-frequency presynaptic stimulation at hippocampal synapses.
AB  - Patterns of short-term synaptic plasticity could considerably differ between
      synapses of the same axon. This may lead to separation of synaptic receptors
      transmitting either low- or high-frequency signals and, therefore, may have
      functional consequences for the information transfer in the brain. Here, we
      estimated a degree of such separation at hippocampal GABAergic synapses using a
      use-dependent GABAA receptor antagonist, picrotoxin, to selectively suppress a
      pool of GABAA receptors monosynaptically activated during the low-frequency
      stimulation. The relative changes in postsynaptic responses evoked by the high
      frequency stimulation before and after such block were used to estimate the
      contribution of this GABAA receptor pool to synaptic transmission at high
      frequencies. Using this approach, we have shown that IPSCs evoked by low
      frequency (0.2 Hz) stimulation and asynchronous currents evoked by high-frequency
      (20-40 Hz) stimulation are mediated by different pools of postsynaptic GABAA
      receptors. Thus, our findings suggest that inhibition produced by a single
      hippocampal interneuron may be selectively routed to different postsynaptic
      targets depending on the presynaptic discharge frequency.

PMID- 24677450
TI  - Urea-based porous organic frameworks: effective supports for catalysis in neat
      water.
AB  - Two urea-based porous organic frameworks, UOF-1 and UOF-2, were synthesized
      through a urea-forming condensation of 1,3,5-benzenetriisocyanate with 1,4
      diaminobenzene and benzidine, respectively. UOF-1 and UOF-2 possess good
      hydrophilic properties and high scavenging ability for palladium. Their palladium
      polymers, PdII/UOF-1 and PdII/UOF-2, exhibit high catalytic activity and
      selectivity for Suzuki-Miyaura cross-coupling reactions and selective reduction
      of nitroarenes in water. The catalytic reactions can be efficiently performed at
      room temperature. Palladium nanoparticles with narrow size distribution were
      formed after the catalytic reaction and were well dispersed in UOF-1 and UOF-2.
      XPS analysis confirmed the coordination of the urea oxygen atom with palladium.
      SEM and TEM images showed that the original network morphology of UOF-1 and UOF-2
      was maintained after palladium loading and catalytic reactions.

PMID- 24677451
TI  - Self-assembled quantum dot structures in a hexagonal nanowire for quantum
      photonics.
AB  - Two types of quantum nanostructures based on self-assembled GaAs quantumdots
      embedded into GaAs/AlGaAs hexagonal nanowire systems are reported, opening a new
      avenue to the fabrication of highly efficient single-photon sources, as well as
      the design of novel quantum optics experiments and robust quantum optoelectronic
      devices operating at higher temperature, which are required for practical quantum
      photonics applications. 

PMID- 24677452
TI  - An investigation of the interactive effects of the capability for suicide and
      acute agitation on suicidality in a military sample.
AB  - BACKGROUND: According to the interpersonal theory of suicide (1, 2), the
      difficulties inherently associated with death by suicide deter many individuals
      from engaging in suicidal behavior. Consistent with the notion that suicide is
      fearsome, acute states of heightened arousal are commonly observed in individuals
      immediately prior to lethal and near-lethal suicidal behavior. We suggest that
      among individuals who possess elevated levels of the capability for suicide, the
      heightened state of arousal experienced during periods of acute agitation may
      facilitate suicidal behavior in part because it would provide the necessary
      energy to approach a potentially lethal stimulus. Among individuals who are low
      on capability, the arousal experienced during agitation may result in further
      avoidance. METHODS: In the present project we examine how acute agitation may
      interact with the capability for suicide to predict suicidality in a large
      military sample (n = 1,208) using hierarchical multiple regression. RESULTS:
      Results were in line with a priori hypotheses: among individuals high on
      capability, as agitation increases, suicidality increases whereas as agitation
      increases among individuals low on capability, suicidality decreases. Results
      held beyond the effects of thwarted belongingness, perceived burdensomeness, and
      suicidal cognitions. CONCLUSIONS: Beyond further substantiating the link between
      agitation and suicide, findings of the present study provide evidence for the
      construct validity of the acquired capability as well as offer initial evidence
      for moderating role of capability on the effect of agitation on suicide.
      Limitations of the current study highlight a need for future research that
      improves upon the techniques used in the present study. Implications for science
      and practice are discussed.

PMID- 24677453
TI  - Nitrogen-doped graphene oxide quantum dots as photocatalysts for overall water
      splitting under visible light illumination.
AB  - Nitrogen-doped graphene oxide quantum dots exhibit both p- and n-type
      conductivities and catalyze overall water-splitting under visible-light
      irradiation. The quantum dots contain p-n type photochemical diodes, in which the
      carbon sp(2) clusters serve as the interfacial junction. The active sites for H2
      and O2 evolution are the p- and n-domains, respectively, and the reaction mimics
      biological photosynthesis. 

PMID- 24677454
TI  - Early presentation of cystic kidneys in a family with a homozygous INVS mutation.
AB  - Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is
      the most frequent monogenic cause of end-stage renal disease in children.
      Infantile NPHP, often in combination with other features like situs inversus, are
      commonly caused by mutations in the INVS gene. INVS encodes the ciliary protein
      inversin, and mutations induce dysfunction of the primary cilia. In this article,
      we present a family with two severely affected fetuses that were aborted after
      discovery of grossly enlarged cystic kidneys by ultrasonography before 22 weeks
      gestation. Exome sequencing showed that the fetuses were homozygous for a
      previously unreported nonsense mutation, resulting in a truncation in the IQ1
      domain of inversin. This mutation induces nonsense-mediated RNA decay, as
      suggested by a reduced RNA level in fibroblasts derived from the fetus. However,
      a significant amount of mutant INVS RNA was present in these fibroblasts,
      yielding mutant inversin protein that was mislocalized. In control fibroblasts,
      inversin was present in the ciliary axoneme as well as at the basal body, whereas
      in the fibroblasts from the fetus, inversin could only be detected at the basal
      body. The phenotype of both fetuses is partly characteristic of infantile NPHP
      and Potter sequence. We also identified that the fetuses had mild skeletal
      abnormalities, including shortening and bowing of long bones, which may expand
      the phenotypic spectrum associated with INVS mutations.

PMID- 24677455
TI  - Heat- or water-driven malleability in a highly recyclable covalent network
      polymer.

PMID- 24677456
TI  - Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat
      model with endoglin-targeted paramagnetic liposomes using 3T MRI.
AB  - PURPOSE: To evaluate the use of endoglin-targeted paramagnetic liposomes in
      delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging
      in a rat model. MATERIALS AND METHODS: Four liposome preparations, including
      nontargeted paramagnetic liposomes (Gd-SLs), isotype control IgG-coupled
      paramagnetic liposomes (IgG-Gd-SLs), endoglin monoclonal antibody coupled
      paramagnetic liposomes (MAb-Gd-SLs), and biotinylated antibodies (Bio
      MAb)/streptavidin-coupled paramagnetic liposomes (SAv-Gd-SLs) for two-step
      pretargeting imaging, were formulated. All animal experiments were carried out
      with the approval of the Shanghai Animal Care. C6 glioma-bearing Sprague-Dawley
      rats were intravenously injected with gadolinium-diethylenetriaminepentaacetic
      acid (Gd-DTPA) or the previously mentioned liposomes (n = 5) and imaged with MR.
      T1 -weighted MRI was performed before and dynamically repeated after different
      contrast agents were injected. The enhancement features of the tumors were
      compared. RESULTS: The signal enhancement of the tumor in the two-step
      pretargeting group increased by 117.9 +/- 5.3% at the periphery and 109.2 +/-
      3.5% in the center (P = 0.032) at the 8-hour timepoint after SAv-Gd-SLs
      injection. Ring-like enhancement margins were demonstrated at the periphery of
      the tumor in the two-step targeted group. The specificity of the targeted
      liposomes was supported by the competitive study. The signal of peak enhancement
      using MAb-Gd-SLs was 59% less than that of the two-step group and only slightly
      higher than the non-targeted groups. CONCLUSION: The two-step endoglin-targeted
      imaging using biotin-streptavidin interaction was demonstrated to induce intense
      enhancement of the tumor periphery, which implies that this advanced MR molecular
      contrast agent may be suitable for accurately delineating glioma tumor margins.
      J. Magn. Reson. Imaging 2015;41:1056-1064. (c) 2014 Wiley Periodicals, Inc.

PMID- 24677457
TI  - Reevaluating osteopathic medical education for the 21st century and beyond.

PMID- 24677458
TI  - A single graduate medical education accreditation system: ensuring quality
      training for physicians and improved health care for the public.

PMID- 24677459
TI  - Unified graduate medical education accreditation: a better plow.

PMID- 24677460
TI  - Moving from EBM to EBOM: an osteopathic perspective on evidence-based medicine.

PMID- 24677462
TI  - Preliminary outcomes of the Lake Erie College of Osteopathic Medicine's 3-year
      Primary Care Scholar Pathway in osteopathic predoctoral education.
AB  - CONTEXT: In 2007, the Lake Erie College of Osteopathic Medicine initiated its
      Primary Care Scholar Pathway (PCSP), a 3-year osteopathic predoctoral education
      curriculum. OBJECTIVE: To assess preliminary outcomes of the PCSP curriculum.
      METHODS: Scores for the Comprehensive Osteopathic Medical Licensing Examination
      (COMLEX-USA) Levels 1 and 2-Cognitive Evaluation (CE) and pass rates for Level 2
      Performance Evaluation (PE) were obtained for individuals who graduated from the
      PCSP program in 2010, 2011, and 2012. Scores for Levels 1 and 2-CE were compared
      with national mean scores. Acceptance rates for residency programs were also
      recorded. RESULTS: Nineteen PCSP graduates were included in the study: 3
      graduated in 2010, 6 graduated in 2011, and 10 graduated in 2012. Scores for PCSP
      students were not significantly different than national average scores for COMLEX
      USA Levels 1 and 2-CE (P>.05). All 19 PCSP graduates passed the COMLEX-USA Level
      2-PE on the first attempt, and all graduates were accepted into primary care
      residency programs. CONCLUSION: The COMLEX-USA scores of PCSP graduates were
      similar to national mean scores, suggesting that it is possible for osteopathic
      medical students to attain the same level of education as students of 4-year
      programs in less time. A 3-year osteopathic predoctoral education curriculum
      would allow students to complete their education at a reduced cost. This
      potential reduction in debt burden could encourage more students to pursue a
      primary care career and thus could help address the shortage of primary care
      physicians in the United States.

PMID- 24677463
TI  - Student- and faculty-reported importance of science prerequisites for osteopathic
      medical school: a survey-based study.
AB  - CONTEXT: The relevance of current standard medical school science prerequisites
      is being reexamined. OBJECTIVES: (1) To identify which science prerequisites are
      perceived to best prepare osteopathic medical students for their basic science
      and osteopathic manipulative medicine (OMM) coursework and (2) to determine
      whether science prerequisites for osteopathic medical school should be modified.
      METHODS: Preclinical osteopathic medical students and their basic science and OMM
      faculty from 3 colleges of osteopathic medicine were surveyed about the
      importance of specific science concepts, laboratories, and research techniques to
      medical school coursework. Participants chose responses on a 5-point scale, with
      1 indicating "strongly disagree" or "not important" and 5 indicating "strongly
      agree" or "extremely important." Participants were also surveryed on possible
      prerequisite modifications. RESULTS: Student responses (N=264) to the general
      statement regarding prerequisites were "neutral" for basic science coursework and
      "disagree" for OMM coursework, with mean (standard deviation [SD]) scores of 3.37
      (1.1) and 2.68 (1.2), respectively. Faculty responses (N=49) were similar, with
      mean (SD) scores of 3.18 (1.1) for basic science coursework and 2.67 (1.2) for
      OMM coursework. Student mean (SD) scores were highest for general biology for
      basic science coursework (3.93 [1.1]) and physics for OMM coursework (2.5 [1.1]).
      Student mean (SD) scores were lowest for physics for basic science coursework
      (1.79 [1.2]) and organic chemistry for OMM coursework (1.2 [0.7]). Both basic
      science and OMM faculty rated general biology highest in importance (mean [SD]
      scores, 3.73 [0.9] and 4.22 [1.0], respectively). Students and faculty rated
      biochemistry high in importance for basic science coursework (mean [SD] scores of
      3.66 [1.2] and 3.32 [1.2], respectively). For basic science coursework, students
      and faculty rated most laboratories as "important," with the highest mean (SD)
      ratings for general anatomy (students, 3.66 [1.5]; faculty, 3.72 [1.1]) and
      physiology (students, 3.56 [1.7]; faculty, 3.61 [1.1]). For their OMM coursework,
      students rated only general anatomy and physiology laboratories as "important"
      (mean [SD] scores, 3.22 [1.8] and 2.61 [1.6], respectively), whereas OMM faculty
      rated all laboratories as "important" (mean scores, >3). Both student and faculty
      respondents rated research techniques higher in importance for basic science
      coursework than for OMM coursework. For prerequisite modifications, all
      respondents indicated "no change" for biology and "reduce content" for organic
      chemistry and physics. All respondents favored adding physiology and biochemistry
      as prerequisites. CONCLUSION: General biology and laboratory were the only
      standard prerequisites rated as "important." Research techniques were rated as
      "important" for basic science coursework only. Physiology and biochemistry were
      identified as possible additions to prerequisites. It may be necessary for
      colleges of osteopathic medicine to modify science prerequisites to reflect
      information that is pertinent to their curricula.

PMID- 24677464
TI  - Consistency of interrater scoring of student performances of osteopathic
      manipulative treatment on COMLEX-USA Level 2-PE.
AB  - CONTEXT: Assessment of osteopathic manipulative treatment (OMT) is included in
      the National Board of Osteopathic Medical Examiners' Comprehensive Osteopathic
      Medical Licensing Examination-USA Level 2-Performance Evaluation (COMLEX-USA
      Level 2-PE). The scores earned for OMT should be equivalent among all raters
      regardless of which technique is scored or which rater is scoring the
      performance. As a quality assurance measure, selected examination dates and the
      encounters within the administration of COMLEX-USA Level 2-PE are scored by 2
      raters: first by a "live" rater and next by a quality assurance rater. Neither
      rater knows if he or she is the first or second rater. OBJECTIVE: To compare
      candidate's scores recorded for OMT on COMLEX-USA Level 2-PE to determine whether
      differences exist among raters and techniques scored. METHODS: The authors
      evaluated candidate performances that took place from July through November 2012.
      For each performance, 2 raters scored the same technique or different techniques
      using the OMT scoring rubric. Discrepancies between scores were compared using t
      tests. Statistical significance was set at P<.05 for most analyses. RESULTS: Of
      the 708 performances, there was no statistically significant difference in
      scoring whether the OMT raters scored the same technique or different techniques
      when the students performed more than 1. There were no statistically significant
      differences between these results and instances when only a single technique was
      performed and scored. CONCLUSION: The present study provides reliability evidence
      for the use of the global OMT scoring tool in the evaluation of OMT in COMLEX-USA
      Level 2-PE.

PMID- 24677465
TI  - Relationship between COMLEX-USA scores and performance on the American
      Osteopathic Board of Emergency Medicine Part I certifying examination.
AB  - CONTEXT: Few studies have investigated how well scores from the Comprehensive
      Osteopathic Medical Licensing Examination-USA (COMLEX-USA) series predict
      resident outcomes, such as performance on board certification examinations.
      OBJECTIVES: To determine how well COMLEX-USA predicts performance on the American
      Osteopathic Board of Emergency Medicine (AOBEM) Part I certification examination.
      METHODS: The target study population was first-time examinees who took AOBEM Part
      I in 2011 and 2012 with matched performances on COMLEX-USA Level 1, Level 2
      Cognitive Evaluation (CE), and Level 3. Pearson correlations were computed
      between AOBEM Part I first-attempt scores and COMLEX-USA performances to measure
      the association between these examinations. Stepwise linear regression analysis
      was conducted to predict AOBEM Part I scores by the 3 COMLEX-USA scores. An
      independent t test was conducted to compare mean COMLEX-USA performances between
      candidates who passed and who failed AOBEM Part I, and a stepwise logistic
      regression analysis was used to predict the log-odds of passing AOBEM Part I on
      the basis of COMLEX-USA scores. RESULTS: Scores from AOBEM Part I had the highest
      correlation with COMLEX-USA Level 3 scores (.57) and slightly lower correlation
      with COMLEX-USA Level 2-CE scores (.53). The lowest correlation was between AOBEM
      Part I and COMLEX-USA Level 1 scores (.47). According to the stepwise regression
      model, COMLEX-USA Level 1 and Level 2-CE scores, which residency programs often
      use as selection criteria, together explained 30% of variance in AOBEM Part I
      scores. Adding Level 3 scores explained 37% of variance. The independent t test
      indicated that the 397 examinees passing AOBEM Part I performed significantly
      better than the 54 examinees failing AOBEM Part I in all 3 COMLEX-USA levels
      (P<.001 for all 3 levels). The logistic regression model showed that COMLEX-USA
      Level 1 and Level 3 scores predicted the log-odds of passing AOBEM Part I (P=.03
      and P<.001, respectively). CONCLUSION: The present study empirically supported
      the predictive and discriminant validities of the COMLEX-USA series in relation
      to the AOBEM Part I certification examination. Although residency programs may
      use COMLEX-USA Level 1 and Level 2-CE scores as partial criteria in selecting
      residents, Level 3 scores, though typically not available at the time of
      application, are actually the most statistically related to performances on AOBEM
      Part I.

PMID- 24677466
TI  - Concurrent validity of the Osteopathic General Surgery In-Service Examination.
AB  - CONTEXT: Performance on the Osteopathic General Surgery In-Service Examination
      (ISE) has been shown to improve over time for osteopathic general surgery
      residents. The training level-specific concurrent validity of the ISE, however,
      has not been evaluated. OBJECTIVE: To investigate whether residents' scores will
      improve as they move from level 1 through level 5 of the ISE. METHODS: In this
      retrospective study, performance on the ISE was obtained from the American
      College of Osteopathic Surgeons for all of the osteopathic general surgery
      residency programs from 2008 through 2012. The weighted raw score and
      standardized score performance mean and standard deviation were determined across
      training levels. One-way t tests were performed between residency years and ISE
      scores. Parametric statistics were calculated with alpha set to .05. RESULTS: The
      authors evaluated 1952 examinations during the study period. Of the 49 programs
      screened, 33 (67.3%) met inclusion criteria for the present study. Analysis of
      variance tests showed that there was significant variation in raw and
      standardized outcomes between residency levels (both P<.001). One-tailed t tests
      for both raw and standardized outcomes showed that all scores' differences
      between examinee levels were statistically significant (P<.001), with the
      exception of raw scores between level 4 and level 5 examinees (P=.20).
      CONCLUSION: There is near-uniform concurrent validity of the ISE by osteopathic
      general surgery training level. This psychometric characteristic supports the
      construct validity of this standardized test.

PMID- 24677467
TI  - Keyboard data entry use among osteopathic medical students and residents.
AB  - CONTEXT: Candidates taking the Comprehensive Osteopathic Medical Licensing
      Examination-USA Level 2-Performance Evaluation (COMLEX-USA Level 2-PE) are
      currently evaluated on their ability to document clinical findings using a
      handwritten postencounter note. However, keyboard data entry is increasingly used
      for medical documentation. OBJECTIVE: To determine the use and perception of
      keyboard data entry among osteopathic medical students and residents in
      educational and clinical settings. METHODS: A Web-based survey regarding
      frequency of and preference for keyboard data entry was distributed to 9801
      osteopathic medical students, 17,268 osteopathic residents, and 34 clinical deans
      of colleges of osteopathic medicine (COMs). In addition, 31 COMs' clinical skills
      center directors were contacted to participate in a telephone survey about the
      use of keyboard data entry in their centers. RESULTS: A total of 1711 students,
      1198 residents, 14 clinical deans, and 17 clinical skills center directors
      responded to the surveys. The majority of students (872 [51%]) reported using
      electronic keyboard data entry at their COM's clinical skills center for
      postencounter notes. Among respondents, 379 students (23%), 77 residents (9%),
      and 1 clinical dean reported that electronic keyboard data entry is never or
      rarely used during clinical rotations. Most trainees (1592 students [93%], 864
      residents [94%]) reported that they were either comfortable or very comfortable
      with typing. Given the option of recording methods for SOAP (subjective,
      objective, assessment, plan) note findings on the COMLEX-USA Level 2-PE, 7
      clinical deans were unsure of their students' preferences, while the remaining
      favored keyboard data entry (5) over handwriting (2). The majority of student and
      resident respondents would choose keyboard data entry (1009 [60%] and 511 [55%],
      respectively). CONCLUSION: Osteopathic medical students and residents are
      comfortable with typing; they are exposed to and would prefer using an electronic
      form of entry for medical documentation. These results support a conversion from
      written postencounter notes to keyboard data entry of notes on the COMLEX-USA
      Level 2-PE.

PMID- 24677468
TI  - Colleges of osteopathic medicine: substantive changes--an update.
AB  - The American Osteopathic Association Commission on Osteopathic College
      Accreditation (AOA COCA) is recognized by the US Secretary of Education as the
      only accrediting agency for osteopathic predoctoral education. To maintain its
      recognition with the US Secretary of Education, the AOA COCA is required to
      adhere to all federal laws and regulations associated with the recognition of
      accrediting agencies. The authors discuss changes in the policies and procedures
      applicable to review of substantive changes in existing colleges of osteopathic
      medicine. Also included is a review of AOA COCA-approved class sizes of the
      accredited colleges of osteopathic medicine. 

PMID- 24677469
TI  - Citation and correction of deficiencies in osteopathic graduate medical education
      programs: opportunities for improvement.
AB  - Since 2008, the American Osteopathic Association has gathered data on osteopathic
      graduate medical education program compliance with the association's correction
      of deficiencies processes. The purpose of the current article is to look at those
      data to discover trends and identify patterns and areas for improvement for
      osteopathic graduate medical education. In addition to providing quantitative
      data, the author also uses qualitative data to explain why corrective action
      plans are recommended for denial. 

PMID- 24677470
TI  - AOA continuing medical education.
AB  - The author provides an update on the current continuing medical education (CME)
      cycle, which began on January 1, 2013, and will end on December 31, 2015. The
      author also highlights changes to the CME process and the re-engineering of the
      CME program for the current cycle. Topic areas include recent changes in CME
      policies and the challenges associated with awarding and recording credits for
      the 2013-2015 CME cycle. In addition, the article provides information regarding
      online CME. 

PMID- 24677475
TI  - Takotsubo cardiomyopathy.

PMID- 24677476
TI  - Postpartum internal hernia.

PMID- 24677478
TI  - Conformational changes in calcium-sensor proteins under molecular crowding
      conditions.
AB  - Fundamental components of signaling pathways are switch modes in key proteins
      that control start, duration, and ending of diverse signal transduction events. A
      large group of switch proteins are Ca(2+) sensors, which undergo conformational
      changes in response to oscillating intracellular Ca(2+) concentrations. Here we
      use dynamic light scattering and a recently developed approach based on surface
      plasmon resonance to compare the protein dynamics of a diverse set of
      prototypical Ca(2+)-binding proteins including calmodulin, troponin C, recoverin,
      and guanylate cyclase-activating protein. Surface plasmon resonance biosensor
      technology allows monitoring conformational changes under molecular crowding
      conditions, yielding for each Ca(2+)-sensor protein a fingerprint profile that
      reflects different hydrodynamic properties under changing Ca(2+) conditions and
      is extremely sensitive to even fine alterations induced by point mutations. We
      see, for example, a correlation between surface plasmon resonance, dynamic light
      scattering, and size-exclusion chromatography data. Thus, changes in protein
      conformation correlate not only with the hydrodynamic size, but also with a
      rearrangement of the protein hydration shell and a change of the dielectric
      constant of water or of the protein-water interface. Our study provides insight
      into how rather small signaling proteins that have very similar three-dimensional
      folding patterns differ in their Ca(2+)-occupied functional state under crowding
      conditions.

PMID- 24677479
TI  - Effect of space length of mannose ligand on uptake of mannosylated liposome in
      RAW 264.7 cells: In vitro and in vivo studies.
AB  - The most widely used method for increasing uptake on macrophage is specific
      targeting for mannose receptor (MR) presented on macrophages. Efficiency of the
      uptake for MR is influenced by the space length and flexibility of mannose ligand
      in liposome (LP). We prepared mannosylated liposomes (M-EGn-LP-ICG) encapsulated
      indocyanine green (ICG) with mannose ligand of various ethylene glycol units
      (EG), LP-ICG, and mannosylated liposome (M-LP-ICG) incorporated with p
      aminophenyl-alpha-d-mannopyranoside. We studied the effect of space length of the
      mannose ligand in vitro and in vivo with prepared liposomes. A space length of
      two ethylene glycol units at least was needed for uptake by macrophages and the
      uptake was increased as the space length increased up to EG4. We measured near
      infrared (NIR) fluorescence intensity by ICG and the fluorescence value of cell
      associated N-(4-nitrobenzo-2-oxa-1,3-diazole) (NBD) in liposome after cellular
      uptake. M-EG4-LP-ICG showed lower NIR fluorescence intensity but higher NBD
      fluorescence value than M-LP-ICG. The result of pre-treatment with d(+)-mannose
      as an inhibitor showed significant decreasing in uptake of mannosylated LP-ICG
      but no difference in LP-ICG. These were explained that mannosylated LP-ICG was
      taken up by macrophages through the MR and M-EG4-LP-ICG showed more specific
      uptake than M-LP-ICG. We obtained images as time passed in the NIR range after
      intravenous administration using a Balb/c mouse with inflammatory model. The
      results showed high uptake in liver at early time and rapid degradation of
      mannosylated LP-ICG. M-EG4-LP-ICG was more selectively taken up by macrophages
      than M-LP-ICG.

PMID- 24677481
TI  - Copper-catalyzed coupling of oxime acetates with sodium sulfinates: an efficient
      synthesis of sulfone derivatives.
AB  - Sulfone derivatives are important synthetic intermediates. However, the general
      method for their preparation is through traditional coupling reaction: the
      alkylation of sodium sulfinates with phenacyl halides. Based on our previous work
      on sodium sulfinates and oxime acetates, we herein report a novel method for
      sulfone derivatives by oxidative coupling with sodium sulfinates and oxime
      acetates using copper as catalyst. The sulfonylvinylamine products could be
      formed in excellent yields. Upon hydrolysis by silica gel in CH2 Cl2 , beta
      ketosulfones could also be efficiently constructed. Various sulfonylvinylamines
      and beta-ketosulfones were obtained in good to excellent yields under the
      optimized reaction conditions. Mechanistic studies indicated that this
      transformation involved copper-catalyzed N-O bond cleavage, activation of a vinyl
      sp(2) C-H bond, and C-S bond formation. The oxime acetates act as both a
      substrate and an oxidant, thus the reaction needs no additional oxidants or
      additives.

PMID- 24677480
TI  - The efficacies of cell-penetrating peptides in accumulating in large unilamellar
      vesicles depend on their ability to form inverted micelles.
AB  - In this study, the direct translocation of cell-penetrating peptides (CPPs) into
      large unilamellar vesicles (LUVs) was shown to be rapid for all the most commonly
      used CPPs. This translocation led within a few minutes to intravesicular
      accumulation up to 0.5 mM, with no need for a transbilayer potential. The
      accumulation of CPPs inside LUVs was found to depend on CPP sequence, CPP
      extravesicular concentration and phospholipid (PL) composition, either in binary
      or ternary mixtures of PLs. More interestingly, the role of anionic phospholipid
      flip-flopping in the translocation process was ascertained. CPPs enhanced the
      flipping of PLs, and the intravesicular CPP accumulation directly correlated with
      the amount of anionic PLs that had been transferred from the external to the
      internal leaflet of the LUV bilayer, thus demonstrating the transport of
      peptide/lipid complexes as inverted micelles. 

PMID- 24677482
TI  - Combined heterogeneous metal/chiral amine: multiple relay catalysis for versatile
      eco-friendly synthesis.
AB  - Herein is described a versatile and broad synergistic strategy for expansion of
      chemical space and the synthesis of valuable molecules (e.g. carbocycles and
      heterocycles), with up to three quaternary stereocenters, in a highly
      enantioselective fashion from simple alcohols (31 examples, 95:5 to >99.5:0.5
      e.r.) using integrated heterogeneous metal/chiral amine multiple relay catalysis
      and air/O2 as the terminal oxidant. A novel highly 1,4-selective heterogeneous
      metal/amine co-catalyzed hydrogenation of enals was also added to the relay
      catalysis sequences.

PMID- 24677483
TI  - Swallowing, voice, and quality of life after supratracheal laryngectomy:
      preliminary long-term results.
AB  - BACKGROUND: The purpose of this study was to report preliminary long-term
      outcomes after supratracheal laryngectomy (STL). METHODS: Twenty-two male
      patients who underwent STL were involved in this study. Swallowing skills,
      neoglottis motility, and vibrations were videoendoscopically assessed.
      Aerodynamic measures, spectrogram analysis, aspiration pneumonia, body weight
      variations, and voice perceptual assessment were performed. Generic, voice
      related, and swallowing-related quality of life (QOL) were assessed. RESULTS:
      Aspiration was found in 10, 2, and 5 patients, respectively, for liquids,
      semisolids, and solids. Neoglottis motility was generally preserved, whereas
      vibration was impaired. Aerodynamic measures showed a poor performance.
      Perceptual assessment revealed highly dysphonic voices. In only 8 patients, a
      harmonic structure was visible in the spectrograms. Aspiration pneumonia occurred
      in 2 patients. Preoperative weight was maintained in 16 patients. Generic, voice
      related, and swallowing-related QOL revealed satisfied patients. CONCLUSION:
      After STL, swallowing was sufficiently restored and QOL was satisfactory, whereas
      the voice was severely impaired even if oral communication was well preserved.

PMID- 24677485
TI  - Synthesis and structure of a 1-phospha-2-boraacenaphthene derivative and its
      chalcogenation reactions.
AB  - The first stable 1-phospha-2-boraacenaphthene 1 was synthesized by the reduction
      of 1-dimesitylboryl-8-dichlorophosphinonaphthalene (2a) with elemental magnesium,
      and it was fully characterized. The chalcogenation reaction of 1 with elemental
      sulfur or selenium afforded the unique heterocycles, 2-thia- and 2-selena-1
      phospha-3-boraphenalenes 9S and 9Se, respectively, through the insertion of the
      chalcogen atom into a P-B bond of 1. Further chalcogenation of 9 afforded the
      corresponding phosphine chalcogenides. These newly obtained chalcogenated
      compounds have been characterized. The unique dynamic behavior of 2-chalcogena-1
      phospha-3-boraphenalene-1-chalcogenides 10 in solution has also been described.

PMID- 24677484
TI  - Endeavors to access molecular complexity: strategic use of free radicals in
      natural product synthesis.
AB  - Free radicals, which in the past were considered unruly chemical species, have
      become manageable and indispensable for synthetic organic chemistry. The unique
      nature of free radicals has allowed practitioners in organic synthesis to design
      flexible approaches to produce various materials ranging from small molecules to
      polymers. The present Personal Account describes the author's endeavors to create
      molecular complexity by the strategic use of free radicals, with an emphasis on
      the synthesis of bioactive natural products. 

PMID- 24677486
TI  - Mesodermal Fgf10b cooperates with other fibroblast growth factors during
      induction of otic and epibranchial placodes in zebrafish.
AB  - BACKGROUND: Vertebrate otic and epibranchial placodes develop in close proximity
      in response to localized fibroblast growth factor (Fgf) signaling. Although less
      is known about epibranchial induction, the process of otic induction in highly
      conserved, with important roles for Fgf3 and Fgf8 reported in all species
      examined. Fgf10 is also critical for otic induction in mouse, but the only
      zebrafish ortholog examined to date, fgf10a, is not expressed early enough to
      play such a role. A second zebrafish ortholog, fgf10b, has not been previously
      examined. RESULTS: We find that zebrafish fgf10b is expressed at tailbud stage in
      paraxial cephalic mesoderm beneath prospective epibranchial tissue, lateral to
      the developing otic placode. Knockdown of fgf10b does not affect initial otic
      induction but impairs subsequent accumulation of otic cells. Formation of
      epibranchial placodes and ganglia are also moderately impaired. Combinatorial
      disruption of fgf10b and fgf3 exacerbates the deficiency of otic cells and
      eliminates epibranchial induction entirely. Disruption of fgf10b and fgf24 also
      strongly reduces, but does not eliminate, epibranchial induction. CONCLUSIONS:
      fgf10b participates in a late phase of otic induction and, in combination with
      fgf3, is especially critical for epibranchial induction.

PMID- 24677487
TI  - Epitope mapping of monoclonal antibodies for the Deinococcus radiodurans
      bacteriophytochome.
AB  - Bacteriophytochromes (BphP) are phytochrome-like light sensing proteins in
      bacteria, which use biliverdin as a chromophore. In order to study the
      biochemical properties of the DrBphP protein, five (2B8, 2C11, 3B2, 3D2, and 3H7)
      anti-DrBphP monoclonal antibodies were produced through the immunization of mice
      with purified full-length DrBphP and DrBphN (1-321 amino acid) proteins, and
      epitope mapping was then carried out. Among the five antibodies, 2B8 and 2C11
      preferentially recognized the N-terminal region of BphP whereas 3B2, 3D2, and 3H7
      showed preference for the C-terminal region. We performed further epitope mapping
      using recombinant truncated BphP proteins to narrow down their target sequences.
      The results demonstrated that each of the five monoclonal antibodies recognized
      different regions on the DrBphP protein. Additionally, epitopes of 2B8 and 3H7
      antibodies were discovered to be shorter than 10 amino acids (2B8: RDPLPFFPP,
      3H7: PGEIEEA). These two antibodies with such specific recognition epitopes could
      be especially valuable for developing new peptide tags for protein detection and
      purification. 

PMID- 24677488
TI  - Predicting ecosystem carbon balance in a warming Arctic: the importance of long
      term thermal acclimation potential and inhibitory effects of light on
      respiration.
AB  - The carbon balance of Arctic ecosystems is particularly sensitive to global
      environmental change. Leaf respiration (R), a temperature-dependent key process
      in determining the carbon balance, is not well-understood in Arctic plants. The
      potential for plants to acclimate to warmer conditions could strongly impact
      future global carbon balance. Two key unanswered questions are (1) whether short
      term temperature responses can predict long-term respiratory responses to growth
      in elevated temperatures and (2) to what extent the constant daylight conditions
      of the Arctic growing season inhibit leaf respiration. In two dominant Arctic
      species Eriophorum vaginatum (tussock grass) and Betula nana (woody shrub), we
      assessed the extent of respiratory inhibition in the light (RL/RD), respiratory
      response to short-term temperature change, and respiratory acclimation to long
      term warming treatments. We found that R of both species is strongly inhibited by
      light (averaging 35% across all measurement temperatures). In E. vaginatum both
      RL and RD acclimated to the long-term warming treatment, reducing the magnitude
      of respiratory response relative to the short-term response to temperature
      increase. In B. nana, both RL and RD responded to short-term temperature increase
      but showed no acclimation to the long-term warming. The ability to predict plant
      respiratory response to global warming with short-term temperature responses will
      depend on species-specific acclimation potential and the differential response of
      RL and RD to temperature. With projected woody shrub encroachment in Arctic
      tundra and continued warming, changing species dominance between these two
      functional groups, may impact ecosystem respiratory response and carbon balance.

PMID- 24677489
TI  - Epigenome-wide DNA methylation changes with development of arsenic-induced skin
      lesions in Bangladesh: a case-control follow-up study.
AB  - Studies have found an association between aberrant DNA methylation and arsenic
      induced skin lesions. However, little is known about DNA methylation changes over
      time in people who develop arsenic-induced skin lesions. We sought to investigate
      epigenome-wide changes of DNA methylation in people who developed arsenic-induced
      skin lesions in a 10-year period. In 2009-2011, we conducted a follow-up study of
      900 skin lesion cases and 900 controls and identified 10 people who developed
      skin lesions since a baseline survey in 2001-2003. The 10 cases ("New Cases")
      were matched with 10 controls who did not have skin lesions at baseline or follow
      up ("Persistent Controls"). Drinking water and blood samples were collected, and
      skin lesion was diagnosed by the same physician at both time points. We measured
      DNA methylation in blood using Infinium HumanMethylation450K BeadChip, followed
      by quantitative validation using pyrosequencing. Two-sample t-tests were used to
      compare changes in percent methylation between New Cases and Persistent Controls.
      Six CpG (cytosine-phosphate-guanine) sites with greatest changes of DNA
      methylation over time among New Cases were further validated with a correlation
      of 93% using pyrosequencing. One of the validated CpG site (cg03333116; change of
      %methylation was 13.2 in New Cases versus -0.09 in Persistent Controls; P <
      0.001) belonged to the RHBDF1 gene, which was previously reported to be
      hypermethylated in arsenic-exposed cases. We examined DNA methylation changes
      with the development of arsenic-induced skin lesions over time but nothing was
      statistically significant given the small sample size of this exploratory study
      and the high dimensionality of data.

PMID- 24677491
TI  - 25th anniversary article: microstructure dependent bias stability of organic
      transistors.
AB  - Recent studies of the bias-stress-driven electrical instability of organic field
      effect transistors (OFETs) are reviewed. OFETs are operated under continuous gate
      and source/drain biases and these bias stresses degrade device performance. The
      principles underlying this bias instability are discussed, particularly the
      mechanisms of charge trapping. There are three main charge-trapping sites: the
      semiconductor, the dielectric, and the semiconductor-dielectric interface. The
      charge-trapping phenomena in these three regions are analyzed with special
      attention to the microstructural dependence of bias instability. Finally,
      possibilities for future research in this field are presented. This critical
      review aims to enhance our insight into bias-stress-induced charge trapping in
      OFETs with the aim of minimizing operational instability.

PMID- 24677490
TI  - Focal and aberrant prefrontal engagement during emotion regulation in veterans
      with posttraumatic stress disorder.
AB  - BACKGROUND: Collectively, functional neuroimaging studies implicate frontal
      limbic dysfunction in the pathophysiology of posttraumatic stress disorder
      (PTSD), as reflected by altered amygdala reactivity and deficient prefrontal
      responses. These neural patterns are often elicited by social signals of threat
      (fearful/angry faces) and traumatic reminders (combat sounds, script-driven
      imagery). Although PTSD can be conceptualized as a disorder of emotion
      dysregulation, few studies to date have directly investigated the neural
      correlates of volitional attempts at regulating negative affect in PTSD. METHODS:
      Using functional magnetic resonance imaging and a well-validated task involving
      cognitive regulation of negative affect via reappraisal and known to engage
      prefrontal cortical regions, the authors compared brain activation in veterans
      with PTSD (n = 21) and without PTSD (n = 21, combat-exposed controls/CEC),
      following military combat trauma experience during deployments in Afghanistan or
      Iraq. The primary outcome measure was brain activation during cognitive
      reappraisal (i.e., decrease negative affect) as compared to passive viewing
      (i.e., maintain negative affect) of emotionally evocative content of aversive
      images RESULTS: The subjects in both groups reported similar successful reduction
      in negative affect following reappraisal. The PTSD group engaged the dorsolateral
      prefrontal cortex (dlPFC) during cognitive reappraisal, albeit to a lesser extent
      than the CEC group. Although the amygdala was engaged in both groups during
      passive viewing of aversive images, neither group exhibited attenuation of
      amygdala activation during cognitive reappraisal. CONCLUSIONS: Veterans with
      combat-related PTSD showed less recruitment of the dlPFC involved in cognitive
      reappraisal, suggesting focal and aberrant neural activation during volitional,
      self-regulation of negative affective states.

PMID- 24677492
TI  - Porous ongrowth surfaces alter osteoblast maturation and mineralization.
AB  - Implant fixation through osseointegration is essential for the success of
      uncemented total joint arthroplasty, and nature and composition of implant
      surface play a critical role in this process. Despite widespread use of
      uncemented implants, the extent of bone ingrowth into implants is generally only
      a small percentage of the total implant surface. An understanding of the
      processes whereby bone cells grow into and multiply on porous surfaces is
      critical for the design and manufacture of implants that maximize ingrowth and
      implant fixation. A wide variety of implant materials are currently utilized for
      uncemented total joint arthroplasty, including titanium mesh, cobalt chromium
      beads, and tantalum deposited on a carbon network. Despite differences in
      physical and chemical properties of these materials, all have functioned well
      clinically. Therefore, the goals of this study were to compare and contrast the
      effects of these materials on the proliferation, phenotypic maturation, and
      mineralization of osteoblasts. Disks of porous tantalum, titanium mesh, and
      cobalt chromium beaded surfaces were fabricated and processed employing the same
      methods used to produce implants, including packaging and sterilization.
      Preosteoblasts were plated on disks, cellular morphology was evaluated by
      scanning electron microscopy. Osteoblast proliferation was significantly higher
      on the porous tantalum compared to other implant surfaces. Alkaline phosphatase
      activity, osteocalcin secretion, and upregulation of RUNX2 were inversely
      proportional to the rate of proliferation. Mineralization of osteoblasts
      paralleled the rate of proliferation. These findings suggest that proliferation
      of osteoblasts into the interstices of implant materials along with delayed
      maturation were favorable for increased bone ongrowth and ultimately implant
      stabilization.

PMID- 24677493
TI  - Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and
      natural course.
AB  - Autosomal dominant brachyolmia (Type 3, OMIM #113500) belongs to a group of
      skeletal dysplasias caused by mutations in the transient receptor potential
      cation channel, subfamily V, member 4 (TRPV4) gene, encoding a Ca++-permeable,
      non-selective cation channel. The disorder is characterized by disproportionate
      short stature with short trunk, scoliosis and platyspondyly. The phenotypic
      variability and long-term natural course remain inadequately characterized. The
      purpose of this study was to describe a large Swedish family with brachyolmia
      type 3 due to a heterozygous TRPV4 mutation c.1847G>A (p.R616Q) in 11
      individuals. The mutation has previously been detected in another family with
      autosomal dominant brachyolmia [Rock et al., 2008]. Review of hospital records
      and patient assessments indicated that clinical symptoms of brachyolmia became
      evident by school age with chronic pain in the spine and hips; radiographic
      changes were evident earlier. Growth was not affected during early childhood but
      deteriorated with age in some patients due to increasing spinal involvement.
      Affected individuals had a wide range of subjective symptoms with chronic pain in
      the extremities and the spine, and paresthesias. Our findings indicate that
      autosomal dominant brachyolmia may be associated with significant long-term
      morbidity, as seen in this family.

PMID- 24677494
TI  - From intercalation to groove binding: switching the DNA-binding mode of
      isostructural transition-metal complexes.
AB  - The interaction with duplex DNA of a small library of structurally related
      complexes that all contain a d6-metal ion coordinated to either the
      2,2':4,4'':4',4'''-quaterpyridyl ligand or its methylated derivative are
      reported. This library is made up of a mixture of newly synthesised and
      previously reported systems. Despite their structural similarities the complexes
      display an almost 20-fold variation in binding affinities. Although effects due
      to the overall charge of the complexes are apparent, the differences in binding
      characteristics are deeper than this; indeed, in a number of cases, changes in
      overall charge have little effect on binding affinity. Intriguingly, despite
      interacting with DNA through unfused ring systems, although two of the complexes
      studied are groove binders, the majority are non-classical intercalators. A
      rationale for these effects has been obtained through a combination of
      experimental and computational studies.

PMID- 24677495
TI  - Understanding low bandgap polymer PTB7 and optimizing polymer solar cells based
      on it.
AB  - Solution processed single junction polymer solar cells (PSCs) have been developed
      from less than 1% power conversion efficiency (PCE) to beyond 9% PCE in the last
      decade. The significant efficiency improvement comes from progress in both
      rational design of donor polymers and innovation of device architectures. Among
      all the novel high efficient donor polymers, PTB7 stands out as the most widely
      used one for solar cell studies. Herein the recent development of PTB7 solar
      cells is reviewed. Detailed discussion of basic property, structure property
      relationship, morphology study, interfacial engineering, and inorganic
      nanomaterials incorporation is provided. Possible future directions for further
      increasing the performance of PTB7 solar cells are discussed. 

PMID- 24677496
TI  - Reductions in prescription opioid diversion following recent legislative
      interventions in Florida.
AB  - PURPOSE: Florida has been at the center of the nation's ongoing prescription
      opioid epidemic, with largely unregulated pain clinics and lax prescribing
      oversight cited as significant contributors to the opioid problem in the state.
      METHODS: In an effort to mitigate prescription opioid abuse and diversion in
      Florida, legislative interventions were implemented during 2010 and 2011, which
      included two primary elements: (i) comprehensive legislation to better regulate
      the operation of pain clinics; and (ii) a statewide prescription drug monitoring
      program to promote safer prescribing practices. Using systematic longitudinal
      data collected on a quarterly basis from law enforcement agencies across Florida,
      this report examined changes in prescription opioid diversion rates following
      implementation of these regulatory initiatives. Quarterly diversion rates for
      buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine,
      oxycodone, and tramadol were calculated, and subsequently, hierarchical linear
      models were fit to test for differences in diversion rates over the 15 quarter
      period of interest. RESULTS: Significant declines in diversion rates were
      observed for oxycodone, methadone, and morphine; hydrocodone displayed a
      marginally significant decline. CONCLUSIONS: This study documented reductions in
      statewide opioid diversion rates following implementation of Florida's pain
      clinic and prescription drug monitoring program legislative interventions.
      Although these initial findings appear promising, continued surveillance of
      diversion is clearly warranted.

PMID- 24677497
TI  - Apparent diffusion coefficient (ADC) measurement in endometrial carcinoma: effect
      of region of interest methods on ADC values.
AB  - PURPOSE: To investigate the influence of different-shaped regions of interest
      (ROIs) on tumor apparent diffusion coefficient (ADC) measurements and
      interobserver variability in endometrial carcinoma. MATERIALS AND METHODS: Sixty
      nine patients (age range, 32-92 years; mean, 61 years) were evaluated in this
      retrospective study. Patients had undergone magnetic resonance (MR) examinations
      including diffusion-weighted imaging (DWI) using a 3.0-T MR system. Two readers
      measured tumor ADCs using four ROI methods: freehand ROI; square ROI; round ROI;
      and five small, round ROIs. Minimum and mean ADCs were obtained. The interclass
      correlation coefficient (ICC) was statistically analyzed to assess measurement
      reliability. Repeated-measures analysis of variance was used for comparisons of
      ADCs measured with each ROI method. RESULTS: ICCs were 0.93 (minimum ADC) / 0.93
      (mean ADC) for freehand ROIs, 0.94/0.95 for square ROIs, 0.94/0.95 for round
      ROIs, and 0.95/0.96 for five small, round ROIs. All ROI methods indicated
      excellent correlations. Each minimum ADC was significantly different except
      between square ROI and round ROI (P < 0.001). Mean ADCs showed significant
      differences only between freehand ROI and the other ROI methods (P < 0.001).
      CONCLUSION: ROI shape has no marked influence on ICC in endometrial carcinoma.
      Compared with minimum ADCs, mean ADCs are suggested to provide more stable
      results regardless of the ROI method.

PMID- 24677498
TI  - Cytochrome P450 as dimerization catalyst in diketopiperazine alkaloid
      biosynthesis.
AB  - As dimeric natural products frequently exhibit useful biological activities,
      identifying and understanding their mechanisms of dimerization is of great
      interest. One such compound is (-)-ditryptophenaline, isolated from Aspergillus
      flavus, which inhibits substance P receptor for potential analgesic and anti
      inflammatory activity. Through targeted gene knockout in A. flavus and
      heterologous yeast gene expression, we determined for the first time the gene
      cluster and pathway for the biosynthesis of a dimeric diketopiperazine alkaloid.
      We also determined that a single cytochrome P450, DtpC, is responsible not only
      for pyrroloindole ring formation but also for concurrent dimerization of N
      methylphenylalanyltryptophanyl diketopiperazine monomers into a homodimeric
      product. Furthermore, DtpC exhibits relaxed substrate specificity, allowing the
      formation of two new dimeric compounds from a non-native monomeric precursor,
      brevianamide F. A radical-mediated mechanism of dimerization is proposed.

PMID- 24677499
TI  - 9-Membered carbocycle formation: development of distinct Friedel-Crafts
      cyclizations and application to a scalable total synthesis of (+/-)-caraphenol A.
AB  - Explorations into a series of different approaches for 9-membered carbocycle
      formation have afforded the first reported example of a 9-exo-dig ring closure
      via a Au(III)-promoted reaction between an alkyne and an aryl ring as well as
      several additional, unique Friedel-Crafts-type cyclizations. Analyses of the
      factors leading to the success of these transformations are provided, with the
      application of one of the developed 9-membered ring closures affording an
      efficient and scalable synthesis of the bioactive resveratrol trimer caraphenol
      A. That synthesis proceeded with an average yield of 89% per step (7.8% overall
      yield) and has provided access to more than 600 mg of the target molecule.

PMID- 24677500
TI  - Direct synthesis of benzofuro[2,3-b]pyrroles through a radical addition/[3,3]
      sigmatropic rearrangement/cyclization/lactamization cascade.
AB  - A straightforward synthetic method for the construction of benzofuro[2,3-b]pyrrol
      2-ones by a novel domino reaction through a radical addition/[3,3]-sigmatropic
      rearrangement/cyclization/lactamization cascade has been developed. The domino
      reaction of O-phenyl-conjugated oxime ether with an alkyl radical allows the
      construction of two heterocycles with three stereogenic centers as a result of
      the formation of two C-C bonds, a C-O bond, and a C-N bond in a single operation,
      leading to pyrrolidine-fused dihydrobenzofurans, which are not easily accessible
      by existing synthetic methods. Furthermore, asymmetric synthesis of benzofuro[2,3
      b]pyrrol-2-one derivatives through a diastereoselective radical addition reaction
      to a chiral oxime ether was also developed.

PMID- 24677501
TI  - Flexible and transparent silicon-on-polymer based sub-20 nm non-planar 3D FinFET
      for brain-architecture inspired computation.
AB  - An industry standard 8'' silicon-on-insulator wafer based ultra-thin (1 MUm),
      ultra-light-weight, fully flexible and remarkably transparent state-of-the-art
      non-planar three dimensional (3D) FinFET is shown. Introduced by Intel
      Corporation in 2011 as the most advanced transistor architecture, it reveals sub
      20 nm features and the highest performance ever reported for a flexible
      transistor. 

PMID- 24677502
TI  - Copper-catalyzed cross-coupling of boronic esters with aryl iodides and
      application to the carboboration of alkynes and allenes.
AB  - Copper-catalyzed Suzuki-Miyaura-type cross-coupling and carboboration processes
      are reported. The cross-couplings function well with a variety of substituted
      aryl iodides and aryl boronic esters and allows for orthogonal reactivity
      compared to palladium-catalyzed processes. The carboboration method includes both
      alkynes and allenes and provides access to highly substituted and stereodefined
      vinyl boronic esters. The alkyne carboboration method is highlighted in the
      simple one-pot synthesis of Tamoxifen.

PMID- 24677503
TI  - Synthesis and biological activities of simplified analogs of the natural PKC
      ligands, bryostatin-1 and aplysiatoxin.
AB  - Protein kinase C (PKC) isozymes play central roles in signal transduction on the
      cell surface and could serve as promising therapeutic targets of intractable
      diseases like cancer, Alzheimer's disease, and acquired immunodeficiency syndrome
      (AIDS). Although natural PKC ligands like phorbol esters, ingenol esters, and
      teleocidins have the potential to become therapeutic leads, most of them are
      potent tumor promoters in mouse skin. By contrast, bryostatin-1 (bryo-1) isolated
      from marine bryozoan is a potent PKC activator with little tumor-promoting
      activity. Numerous investigations have suggested bryo-1 to be a promising
      therapeutic candidate for the above intractable diseases. However, there is a
      supply problem of bryo-1 both from natural sources and by organic synthesis.
      Recent approaches on the synthesis of bryo-1 have focused on its simplification,
      without decreasing the ability to activate PKC isozymes, to develop new medicinal
      leads. Another approach is to use the skeleton of natural PKC ligands to develop
      bryo-1 surrogates. We have recently identified 10-methyl-aplog-1 (26), a
      simplified analog of tumor-promoting aplysiatoxin (ATX), as a possible
      therapeutic lead for cancer. This review summarizes recent investigations on the
      simplification of natural PKC ligands, bryo-1 and ATX, to develop potential
      medicinal leads. 

PMID- 24677504
TI  - Contrasting long-term records of biomass burning in wet and dry savannas of
      equatorial East Africa.
AB  - Rainfall controls fire in tropical savanna ecosystems through impacting both the
      amount and flammability of plant biomass, and consequently, predicted changes in
      tropical precipitation over the next century are likely to have contrasting
      effects on the fire regimes of wet and dry savannas. We reconstructed the long
      term dynamics of biomass burning in equatorial East Africa, using fossil charcoal
      particles from two well-dated lake-sediment records in western Uganda and central
      Kenya. We compared these high-resolution (5 years/sample) time series of biomass
      burning, spanning the last 3800 and 1200 years, with independent data on past
      hydroclimatic variability and vegetation dynamics. In western Uganda, a rapid
      (<100 years) and permanent increase in burning occurred around 2170 years ago,
      when climatic drying replaced semideciduous forest by wooded grassland. At the
      century time scale, biomass burning was inversely related to moisture balance for
      much of the next two millennia until ca. 1750 ad, when burning increased strongly
      despite regional climate becoming wetter. A sustained decrease in burning since
      the mid20th century reflects the intensified modern-day landscape conversion into
      cropland and plantations. In contrast, in semiarid central Kenya, biomass burning
      peaked at intermediate moisture-balance levels, whereas it was lower both during
      the wettest and driest multidecadal periods of the last 1200 years. Here, burning
      steadily increased since the mid20th century, presumably due to more frequent
      deliberate ignitions for bush clearing and cattle ranching. Both the observed
      historical trends and regional contrasts in biomass burning are consistent with
      spatial variability in fire regimes across the African savanna biome today. They
      demonstrate the strong dependence of East African fire regimes on both climatic
      moisture balance and vegetation, and the extent to which this dependence is now
      being overridden by anthropogenic activity.

PMID- 24677505
TI  - Algorithm to predict postoperative complications in oropharyngeal and oral cavity
      carcinoma.
AB  - BACKGROUND: Preoperative data in patients with oral cavity/oropharyngeal cancer
      may predict postoperative complications that may modify therapeutic choices and
      improve patient care. METHOD: We reviewed 320 consecutive patients with oral
      cavity/oropharyngeal cancer, operated on 2003 through 2006 at the European
      Institute of Oncology. By multivariate analysis of preoperative patient and tumor
      characteristics, we developed an algorithm to predict postoperative
      complications. We tested the algorithm on a new series of 307 patients operated
      on 2007 through 2010. RESULTS: The final algorithm used to produce a nomogram was
      comprised of: alcohol consumption (p = .01), site of primary (p = .03),
      interaction of clinical T classification to sex (p = .007), and type of neck
      dissection (p < .0001). The algorithm had good ability to predict complications
      (concordance index [c-index] 0.74) in the new series. CONCLUSION: The nomogram
      accurately predicts presurgical risk of postoperative local/systemic
      complications in patients with oral cavity/oropharyngeal cancer and can be used
      to adapt therapy to patient characteristics, optimize ward admissions, and
      improve care.

PMID- 24677506
TI  - A comparison of dual gradient-echo and spin-echo fMRI of the inferior temporal
      lobe.
AB  - Magnetic susceptibility differences at tissue interfaces lead to signal loss in
      conventional gradient-echo (GE) EPI. This poses a problem for fMRI in language
      and memory paradigms, which activate the most affected regions. Two methods
      proposed to overcome this are spin-echo EPI and dual GE EPI, where two EPI read
      outs are serially collected at a short and longer echo time. The spin-echo method
      applies a refocusing pulse to recover dephased MR signal due to static field
      inhomogeneities, but is known to have a relatively low blood oxygenation level
      dependant (BOLD) sensitivity. In comparison, GE has superior BOLD sensitivity,
      and by employing an additional shorter echo, in a dual GE sequence, it can reduce
      signal loss due to spin dephasing. We directly compared dual GE and spin-echo
      fMRI during a semantic categorization task, which has been shown to activate the
      inferior temporal region-a region known to be affected by magnetic
      susceptibility. A whole brain analysis showed that the dual GE resulted in
      significantly higher activation within the left inferior temporal fusiform (ITF)
      cortex, compared to spin-echo. The inferior frontal gyrus (IFG) was activated for
      dual GE, but not spin-echo. Regions of interest analysis was carried out on the
      anterior and posterior ITF, left and right IFG, and part of the cerebellum. Dual
      GE outperformed spin-echo in the anterior and posterior ITF and bilateral IFG
      regions, whilst being equal in the cerebellum. Hence, dual GE should be the
      method of choice for fMRI studies of inferior temporal regions.

PMID- 24677507
TI  - Thiazolidinones derived from dynamic systemic resolution of complex reversible
      reaction networks.
AB  - A complex dynamic system based on a network of multiple reversible reactions has
      been established. The network was applied to a dynamic systemic resolution
      protocol based on kinetically controlled lipase-catalyzed transformations. This
      resulted in the formation of cyclized products, where two thiazolidinone
      compounds were efficiently produced from a range of potential transformations.

PMID- 24677508
TI  - Distinct roles for hu li tai shao and swallow in cytoskeletal organization during
      Drosophila oogenesis.
AB  - BACKGROUND: Cytoskeletal organization is essential for localization of
      developmentally significant molecules during Drosophila oogenesis. Swallow (Swa)
      and an isoform of Hu li tai shao (Ovhts-RC) have been implicated in the
      organization of actin filaments in developing oocytes but their precise roles
      have been obscured by the dependence of hts RNA localization on swa function. The
      functional significance of hts RNA localization in the oocyte has not been
      established. RESULTS: In this study we examine Ovhts-RC distribution and
      cytoskeletal organization under conditions in which Swa protein and/or hts RNA
      localization are perturbed. We find Swa is required for overall actin
      organization and for the maintenance of a distinct subset of microtubules in the
      oocyte. hts RNA localization modulates the distribution of Ovhts-RC in the oocyte
      and, in turn, local actin filament proliferation. CONCLUSIONS: Our results
      support separate contributions of Swa and hts RNA localization to actin
      organization during oogenesis. Swa is crucial for the organization of actin
      networks that lead to the formation of a specialized microtubule population,
      while Ovhts-RC acts to modulate spatially restricted actin filament growth at the
      oocyte cortex. This suggests RNA localization can lead to modifications of both
      the actin and microtubule cytoskeletons at specific subcellular locales.

PMID- 24677510
TI  - A dithienylethene-based rewritable hydrogelator.
AB  - Dithienylethene photochromic switching units have been incorporated into a
      hydrogelating system based on a tripeptide motif. The resulting hybrid system
      provided both a photochromic response and the ability to gelate water under
      acidic and neutral conditions. Fluorescence spectroscopy shows that the
      dithienylethene units are in sufficient proximity to each other to stack in gel
      fibers, with the tripeptide unit determining solubility. TEM measurements
      provided insight into the microscopic structure of the fibers formed.

PMID- 24677509
TI  - Crystal structure of toxin HP0892 from Helicobacter pylori with two Zn(II) at 1.8
      A resolution.
AB  - Antibiotic resistance and microorganism virulence have been consistently
      exhibited by bacteria and archaea, which survive in conditions of environmental
      stress through toxin-antitoxin (TA) systems. The HP0892-HP0893 TA system is one
      of the two known TA systems belonging to Helicobacter pylori. The antitoxin,
      HP0893, binds and inhibits the HP0892 toxin and regulates the transcription of
      the TA operon. Here, we present the crystal structure of the zinc-bound HP0892
      toxin at 1.8 A resolution. Reorientation of residues at the mRNase active site
      was shown. The involved residues, namely E58A, H86A, and H58A/ H60A, were mutated
      and the binding affinity was monitored by ITC studies. Through the structural
      difference between the apo and the metal-bound state, and using a homology
      modeling tool, the involvement of the metal ion in mRNase active site could be
      identified. The most catalytically important residue, His86, reorients itself to
      exhibit RNase activity. His47, Glu58, and His60 are involved in metal binding
      where Glu58 acts as a general base and His47 and His60 may also act as a general
      acid in enzymatic activity. Glu58 and Asp64 are involved in substrate binding and
      specific sequence recognition. Arg83 is involved in phosphate binding and
      stabilization of the transition state, and Phe90 is involved in base packing and
      substrate orientation. 

PMID- 24677511
TI  - The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates
      IL17A-induced levels of IL6 in human astrocytes.
AB  - The family of interleukin 17 receptors (IL17Rs), subtypes IL17RA-IL17RE, is
      targeted by the group of pro-inflammatory IL17 cytokines (IL17A-F) and moreover
      the newly developed anti-IL17A antibody secukinumab (AIN457) has shown promise in
      Phase II trials in multiple sclerosis. Here, we show that human astrocytes,
      isolated from a fetal cerebral cortex, express IL17RA and IL17RC and in vitro
      treatment with IL17A increases protein levels of IL6 in human astrocytes, which
      is enhanced in the presence of TNFalpha, as determined by homogeneous time
      resolved fluorescence. Studies on acutely isolated mouse astrocytes are
      comparable to human astrocytes although the protein levels of IL6 are lower in
      mouse astrocytes, which also show a lower response to IL17F and IL1beta in
      promoting IL6 levels. In human astrocytes, IL17A and TNFalpha also induce mRNA
      expression of IL6, IL8 and the Th17 cytokines CXCL1, CXCL2, and CCL20, with
      little effect on Th1 cytokines CXCL9, CXCL10, and CXCL11. The effects of IL17A
      are associated with nuclear translocation of the NF-kappaB transcription factor,
      as determined by immunocytochemistry, where treatment of human astrocytes with
      the inhibitors of the NF-kappaB pathway and with secukinumab inhibits the IL17A
      and IL17A/TNFalpha-induced increase in nuclear translocation of NF-kappaB and
      levels of IL6. Taken together the data shows that IL17A signaling plays a key
      role in regulating the levels of cytokines, such as IL6, in human astrocytes via
      a mechanism that involves NF-kappaB signaling and that selective inhibition of
      IL17A signaling attenuates levels of pro-inflammatory molecules in astrocytes.

PMID- 24677512
TI  - Cytogenomic and phenotypic analysis in low-level monosomy 7 mosaicism with non
      supernumerary ring chromosome 7.
AB  - We present the literature review of ring chromosome 7 and clinical, cytogenetic
      and fine molecular mapping of the first postnatal report of a male child with a
      non-supernumerary ring chromosome 7, r(7). The patient had dysmorphic features,
      developmental delay, dermatologic lesions with variable pigmentation,
      hypogenitalism, lumbar dextroscoliosis, cerebellar and ophthalmological
      abnormalities, and melanocytic congenital nevi. Cytogenetic analysis of
      peripheral blood and the nevus sample showed the presence of three different cell
      lines r(7), monosomy 7, and duplicated r(7) (idic r(7)), while findings on
      fibroblasts from both light and dark skin showed only mosaicism with r(7) and
      monosomy 7 cell lines in various proportions. FISH assay of the ring chromosome
      showed subtelomeric loss in both chromosome arms in all tissues studied. Analysis
      by genome-wide single-nucleotide polymorphism array showed a 0.8 Mb deletion in
      7p22.3 (involving eight genes) and a 7.5 Mb deletion in 7q36 (involving 29 genes
      including some involved in genital and central nervous system development). The
      combination of results from our karyotypic and array analyses enabled us to
      establish an accurate genotype-phenotype relationship.

PMID- 24677513
TI  - All organic sodium-ion batteries with Na4C8H2O6.
AB  - Developing organic compounds with multifunctional groups to be used as electrode
      materials for rechargeable sodium-ion batteries is very important. The organic
      tetrasodium salt of 2,5-dihydroxyterephthalic acid (Na4DHTPA; Na4C8H2O6), which
      was prepared through a green one-pot method, was investigated at potential
      windows of 1.6-2.8 V as the positive electrode or 0.1-1.8 V as the negative
      electrode (vs. Na(+)/Na), each delivering compatible and stable capacities of ca.
      180 mAh g(-1) with excellent cycling. A combination of electrochemical,
      spectroscopic and computational studies revealed that reversible uptake/removal
      of two Na(+) ions is associated with the enolate groups at 1.6-2.8 V
      (Na2C8H2O6/Na4C8H2O6) and the carboxylate groups at 0.1-1.8 V
      (Na4C8H2O6/Na6C8H2O6). The use of Na4C8H2O6 as the initial active materials for
      both electrodes provided the first example of all-organic rocking-chair SIBs with
      an average operation voltage of 1.8 V and a practical energy density of about 65
      Wh kg(-1).

PMID- 24677515
TI  - Templated self-assembly of functional oxide nanocomposites.
AB  - In perovskite/spinel self-assembled oxide nanocomposites, the substrate surface
      plays a dominant role in determining the final morphology. Topgraphic features,
      such as pits and trenches, are written in the substrate using either Focused Ion
      Beam or wet etching through a block co-polymer mask. These features are effective
      at templating the self-assembly, resulting in a wide range of attainable nano
      assemblies. 

PMID- 24677514
TI  - Gold-catalyzed cascade reactions for synthesis of carbo- and heterocycles:
      selectivity and diversity.
AB  - This account describes our recent efforts devoted to gold chemistry since 2009.
      Based on furyl-Au 1,3-dipole analogues and related gold carbene intermediates, a
      rich variety of gold-catalyzed cascade reactions have been developed, which
      provide facile access to a diverse range of novel carbo- and heterocycles. In
      these reactions, the selectivity can be well controlled by the catalyst (ligand
      and metal), substrate or reagent. In addition, we have also developed the
      corresponding enantioselective variants, which are guided by bis(phosphinegold)
      complexes derived from axially chiral scaffolds and asymmetric gold/chiral
      Bronsted acid relay catalysis. 

PMID- 24677516
TI  - Clinical outcome of patients with carcinoma ex pleomorphic adenoma of the parotid
      gland: a comparative study from a single tertiary center.
AB  - BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland is a
      high-grade cancer and the prognosis of this cancer has not been compared with non
      CXPA high-grade primary parotid cancer. METHODS: Retrospective medical chart
      review of patients with surgically treated high-grade primary parotid cancer (21
      CXPA and 52 non-CXPA) was performed with correlation with disease-specific
      survival, locoregional recurrence, and distant recurrence. RESULTS: Despite
      having similar stage of cancer and extent of surgical resection, patients with
      CXPA had a lower disease-specific survival compared to non-CXPA high-grade
      primary parotid cancer (p = .02). Salivary duct cancer (SDC) was the commonest
      histologic variant in both cohorts and around 40% of patients with SDC died of
      distant recurrence that occurred within 3 years from diagnosis. CONCLUSION: CXPA
      of the parotid gland is a more aggressive cancer compared to non-CXPA high-grade
      primary parotid cancer. SDC was associated with a high chance of delayed distant
      recurrence, which contributed directly to the mortality of this cancer.

PMID- 24677517
TI  - Measurement accuracy of different active tracking sequences for interventional
      MRI.
AB  - PURPOSE: To compare the spatial accuracy of three typical active tracking
      sequences using a new, unique phantom design. MATERIALS AND METHODS: Three
      different tracking sequences (Single Echo, Dual Echo and Hadamard Multiplexed)
      were compared with each other in a phantom study with respect to their positional
      accuracy. A custom-built phantom was constructed to conduct the experiments with
      precise framework conditions which facilitated sufficient measurement accuracy.
      An electrophysiology catheter incorporating four micro-coils was used as an
      interventional device. Tracking profiles were acquired in all three spatial
      dimensions and validated against the distances that were measured by a Vernier
      caliper in combination with a three-dimensional reference scan. RESULTS: The
      Bland-Altman plots demonstrated that all three sequences show < 1.5 mm positional
      error. The measurement accuracy of Single Echo and Double Echo are prone to off
      resonances, whereas Hadamard Encoding is immune to it. CONCLUSION: The developed
      phantom enabled the performance of objective measurements of the accuracy of
      different active tracking sequences. The proposed setup allows for objectively
      contrasting different methods for interventional procedures.

PMID- 24677518
TI  - Taming the first-order transition in giant magnetocaloric materials.
AB  - Large magnetically driven temperature changes are observed in MnFe(P,Si,B)
      materials simultaneously with large entropy changes, limited (thermal or
      magnetic) hysteresis, and good mechanical stability. The partial substitution of
      B for P in MnFe(P,Si) compounds is found to be an ideal parameter to control the
      latent heat observed at the Curie point without deteriorating the magnetic
      properties, which results in promising magnetocaloric properties suitable for
      magnetic refrigeration. 

PMID- 24677519
TI  - Photodegradation of bisphenol A in aqueous medium: monitoring and identification
      of by-products by liquid chromatography coupled to high-resolution mass
      spectrometry.
AB  - RATIONALE: Environmental bisphenol A (BPA) contamination is currently a matter of
      concern. This compound can disrupt the endocrine system by mimicking natural
      hormones and cause adverse effects on different organisms. In addition, it has
      been suggested that BPA can impair brain development, especially in fetuses and
      children. To efficiently remove BPA from contaminated water and wastewaters,
      several emerging technologies have been developed. Most are based on
      photodegradation. However, by-products resulting from the application of such
      methods have not been properly characterized. METHODS: The photodegradation of
      BPA was conducted using two different methods: photocatalysis (TiO2/UV-A and
      TiO2/UV-C systems) and direct photolysis (UV-A and UV-C radiation). The
      degradation process was continuously monitored to identify and observe the by
      products formed under these conditions. Direct infusion electrospray ionization
      coupled to high-resolution mass spectrometry in negative ion mode [ESI(-)-HRMS]
      and liquid chromatography coupled to high-resolution mass spectrometry
      (HPLC/HRMS) were employed to monitor these by-products. RESULTS: The results
      revealed that the TiO2/UV-C system was the most efficient in causing both BPA
      depletion and mineralization of the organic matter in solution. Moreover,
      accurate mass data allowed for the assignment of molecular formulae for seven by
      products, many of them unprecedented, formed under these conditions. Thus, a
      route for the photodegradation of BPA in aqueous medium could be proposed based
      on these results. Finally, additional tests revealed that the by-products showed
      a higher toxicity against Artemia salina than the primary precursor. CONCLUSIONS:
      All of these findings indicate that the identification of by-products arising
      from oxidative treatments is of primary importance because such compounds can be
      more hazardous than their precursors.

PMID- 24677520
TI  - Using a single, high mass resolution mass spectrometry platform to investigate
      ion suppression effects observed during tissue imaging.
AB  - RATIONALE: The signal intensity of a given molecule across a tissue section when
      measured using mass spectrometry imaging (MSI) is prone to changes caused by the
      molecular heterogeneity across the surface of the tissue. Here we propose a
      strategy to investigate these effects using electrospray ionization (ESI) and
      matrix-assisted laser desorption/ionization (MALDI) on a single high-resolution
      mass spectrometry (HRMS) platform. METHODS: A rat was administered with a single
      inhaled dose of a compound and sacrificed 1 h after dosing. Sections were
      prepared from the excised frozen lung and analysed using MALDI, liquid extraction
      surface analysis (LESA) nano-ESI-MS and nano-ESI liquid chromatography (LC)/MS.
      The ESI and MALDI ion sources were mounted either side of the ion transfer system
      of the same Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer.
      RESULTS: MALDI MSI clearly demonstrated widespread distribution of the dosed
      molecule throughout the lung, with the exception of a non-lung section of tissue
      on the same sample surface. Comparison of the lipid signals across the sample
      indicated a change in signal between the lung and the adipose tissue present on
      the same section. Use of ESI and MALDI, with and without an internal standard,
      supported the evaluation of changes in the signal of the dosed molecule across
      the tissue section. CONCLUSIONS: The results demonstrate the successful
      application of a dual ion source HRMS system to the systematic evaluation of data
      from MALDI MSI, used to determine the distribution of an inhaled drug in the
      lung. The system discussed is of great utility in investigating the effects of
      ion suppression and evaluating the quantitative and qualitative nature of the MSI
      data.

PMID- 24677521
TI  - Elucidation of electron ionization mass spectrometric fragmentation pathways of
      trimethylsilyl ether derivatives of vicinal diols deriving from haplamine by
      collision-induced dissociation gas chromatography/tandem mass spectrometry and
      18O labelling.
AB  - RATIONALE: Formation of vicinal diols was observed after in vitro and in vivo
      studies of the natural product haplamine (9-methoxy-2,2-dimethyl-2,6
      dihydropyrano[3,2-c]quinolin-5-one). These compounds, identified as trans- and
      cis-3,4-dihydroxy-9-methoxy-2,2-dimethyl-2,3,4,6-tetrahydropyrano[3,2-c]quinolin
      5-ones and trans- and cis-3,4,9-trihydroxy-2,2-dimethyl-2,3,4,6
      tetrahydropyrano[3,2-c]quinolin-5-ones, have a potential interest in oncology. It
      is therefore essential to elucidate their electron ionization mass spectrometric
      (EIMS) fragmentation pathways. METHODS: EIMS fragmentation pathways of
      trimethylsilyl (TMS) derivatives of 3,4-dihydroxy- and 3,4,9-trihydroxyhaplamines
      were investigated. These pathways have been substantiated by: (i) comparison with
      EI mass spectra of structural homologues (silylated diols obtained from various
      chromenes and 1,2-dihydronaphthalene), (ii) low-energy collision-induced
      dissociation (CID) gas chromatography/tandem mass spectrometry (GC/MS/MS) and
      (iii) (18)O labelling. RESULTS: CID-MS/MS analyses and (18)O labelling
      demonstrated that EI mass spectral fragmentation of these TMS derivatives
      involves a transannular cleavage of the pyran ring with formation of a
      characteristic intense cyclic ion. The study of the mass spectra of TMS
      derivatives of different chromenes and 1,2-dihydroxynaphthalene allowed to
      confirm the proposed fragmentation pathways and to show that they act only when
      the pyran ring is present. CONCLUSIONS: Elimination of the neutral element
      [(CH3)2=C(H)OSi(CH3)3] and formation of cyclic ions play a key role during EI
      mass spectral fragmentation of the TMS derivatives of 3,4-dihydroxy- and 3,4,9
      trihydroxyhaplamines. These fragmentation pathways could be generalized to TMS
      derivatives of cyclic compounds possessing vicinal diols close to a pyran ring.

PMID- 24677522
TI  - Isotopic turnover of carbon and nitrogen in bovine blood fractions and inner
      organs.
AB  - RATIONALE: Isotope ratio analysis of bovine tissues is a tool for inferring
      aspects of the dietary history of cattle. The objective of this experiment was to
      quantify the carbon (C) and nitrogen (N) isotopic turnover in blood (serum and
      residue) and inner organs (liver, kidney, heart and brain) of beef cattle.
      METHODS: Growing beef cattle (n = 70 in total) were either switched from a
      control diet containing barley and urea to an experimental diet containing maize
      and (15)N-enriched urea, for various intervals prior to slaughter or maintained
      on the control diet for 168 days pre-slaughter. Samples of blood, liver, kidney,
      heart and brain were collected at 0, 14, 28, 56, 112 and 168 days and analysed
      using Isotope Ratio Mass Spectrometry. RESULTS: After 168 days, C- and N-isotopic
      equilibrium was reached in the blood serum, liver and kidney, approached in the
      heart and brain, but not reached in the non-serum component of blood. The
      estimated C and N half-lives were 16.5 and 20.7 days for liver, 19.2 and 25.5
      days for kidney, 29.2 and 35.6 days for blood serum, 37.6 and 49.9 days for
      heart, 53.3 and 52.2 days for brain and 113.3 and 115.0 days for the non-serum
      blood residue, respectively. Modelling the C and N turnover in the different
      tissue combinations revealed that a combined analysis of liver and heart as well
      as brain and kidney can provide the most accurate estimation of the timing of the
      diet switch. CONCLUSIONS: Based on the difference in turnover rates, bovine soft
      tissues can provide isotopic information on short- and long-term dietary changes,
      which in turn may be linked to the geographic or production origin of beef
      cattle. This study also provides basic biological data on organ C and N turnover
      in a large herbivorous mammal.

PMID- 24677523
TI  - Combined 13C and 15N isotope analysis on small samples using a near-conventional
      elemental analyzer/isotope ratio mass spectrometer setup.
AB  - RATIONALE: A high sensitivity elemental analyzer/isotope ratio mass spectrometer
      setup was developed to allow analysis of (13)C and (15)N isotopic composition on
      microgram amounts of C and N, respectively. METHODS: Increased sensitivity of a
      conventional elemental analyzer equipped with a low blank autosampler was
      obtained by decreased carrier gas flow of 35 mL/min. The diameters of the
      oxidation and reduction reactors and water trap were reduced to 7.8, 7.8 and 4 mm
      i.d., respectively, to obtain sharp sample peaks in the mass spectrometer. To
      increase the lifetime of the reduction reactor, a 1:1 He/O2 mixture was used as
      oxidizing agent in the elemental analyzer. RESULTS: Sample amounts of 0.6 ug N
      and 1 ug C were sufficient for accurate isotopic analysis with <1 0/00 standard
      error after blank correction. One major advantage of the setup is the easy
      switching between conventional EA and MUEA as only consumable parts need to be
      exchanged. CONCLUSIONS: The proposed setup proved to be suitable to analyze
      minute amounts of C and N in one analytical run simultaneously.

PMID- 24677524
TI  - Can two-dimensional gas chromatography/mass spectrometric identification of
      bicyclic aromatic acids in petroleum fractions help to reveal further details of
      aromatic hydrocarbon biotransformation pathways?
AB  - RATIONALE: The identification of key acid metabolites ('signature' metabolites)
      has allowed significant improvements to be made in our understanding of the
      biodegradation of petroleum hydrocarbons, in reservoir and in contaminated
      natural systems, such as aquifers and seawater. On this basis, anaerobic
      oxidation is now more widely accepted as one viable mechanism, for instance.
      However, identification of metabolites in the complex acid mixtures from
      petroleum degradation is challenging and would benefit from use of more highly
      resolving analytical methods. METHODS: Comprehensive two-dimensional gas
      chromatography/time-of-flight mass spectrometry (GCxGC/TOFMS) with both nominal
      mass and accurate mass measurement was used to study the complex mixtures of
      aromatic acids (as methyl esters) in petroleum fractions. RESULTS: Numerous mono-
      and di-aromatic acid isomers were identified in a commercial naphthenic acids
      fraction from petroleum and in an acids fraction from a biodegraded petroleum. In
      many instances, compounds were identified by comparison of mass spectral and
      retention time data with those of authentic compounds. CONCLUSIONS: The
      identification of a variety of alkyl naphthalene carboxylic and alkanoic and
      alkyl tetralin carboxylic and alkanoic acids, plus identifications of a range of
      alkyl indane acids, provides further evidence for 'signature' metabolites of
      biodegradation of aromatic petroleum hydrocarbons. Identifications such as these
      now offer the prospect of better differentiation of metabolites of bacterial
      processes (e.g. aerobic, methanogenic, sulphate-reducing) in polar petroleum
      fractions.

PMID- 24677525
TI  - Structural speculation and identification of alkaloids in Macleaya cordata fruits
      by high-performance liquid chromatography/quadrupole-time-of-flight mass
      spectrometry combined with a screening procedure.
AB  - RATIONALE: Alkaloids with significant therapeutic effects are the main active
      constituents of Macleaya cordata, which is a perennial herb plant in the
      Papaveraceae family. A systematic and novel method for speculating and
      identifying the structures of alkaloids in M. cordata fruits by high-performance
      liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/Q-TOF-MS)
      with a screening procedure was reported. METHODS: Investigation of mass spectral
      fragmentation of alkaloids was carried out based on the tandem mass spectrometry
      (MS/MS) data analyses of eight reference substances. The skeletons of alkaloids
      were determined by their ultraviolet spectra (UV) and MS/MS data. The substituent
      groups of the alkaloids were acquired through a screening procedure developed in
      our laboratory and MS/MS data. The substituent linkage sites were deduced by
      MS/MS fragmentation behavior, as well as biosynthetic pathways of related
      alkaloids. RESULTS: The structures of 21 alkaloids were speculated in this study,
      10 of which were reported for the first time in M. cordata. Furthermore,
      benzyltetrahydroisoquinoline and N-methyltetrahydroprotoberberine-type alkaloids
      were discovered, which indirectly proved that the biosynthetic pathways of
      benzophenanthridine alkaloids reported in Eschscholtzia california existed in M.
      cordata as well. CONCLUSIONS: HPLC/Q-TOF-MS combined with a screening procedure
      was a systematic and reliable method for speculating and elucidating the
      structures of alkaloids. This study might be useful for the identification of
      other compounds in herbal medicines.

PMID- 24677526
TI  - Identifying the proton transfer reaction mechanism via a proton-bound dimeric
      intermediate for esomeprazoles by a kinetic method combined with density
      functional theory calculations.
AB  - RATIONALE: Esomeprazole analogs are a class of important proton pump inhibitors
      for the treatment of gastro-esophageal reflux diseases. Understanding the
      fragmentation reaction mechanism of the protonated esomeprazole analogs will
      facilitate the characterization of their complex metabolic fate in humans. In
      this paper, the kinetic method and theoretical calculations were applied to
      evaluate the fragmentation of protonated esomeprazole analogs. METHODS: All
      collision-induced dissociation (CID) mass spectrometry experiments were carried
      out using electrospray ionization (ESI) ion trap mass spectrometry in positive
      ion mode. Also the accurate masses of fragments were measured on by ESI
      quadrupole time-of-flight (QTOF) MS in positive ion mode. Theoretical
      calculations were carried out by the density functional theory (DFT) method with
      the 6-31G(d) basis set in the Gaussian 03 program. RESULTS: In the fragmentation
      of the protonated esomeprazole analogs, C-S bond breakage is observed, which
      gives rise to protonated 2-(sulfinylmethylene)pyridines and protonated
      benzimidazoles. DFT calculations demonstrate that the nitrogen atom of the
      pyridine part is the thermodynamically most favorable protonation site, and the C
      S bond cleavage is triggered by the transfer of this ionizing proton from the
      nitrogen atom of the pyridine part to the carbon atom of the benzimidazole part
      to which the sulfinyl is attached. Moreover, with the kinetic plot, the intensity
      ratios of two protonated product ions yield a linear relationship with the
      differences in proton affinities of the corresponding neutral molecules, which
      provides strong experimental evidence that the reaction proceeds via proton-bound
      2-(sulfinylmethylene)pyridine/benzimidazole complex intermediates. CONCLUSIONS:
      The kinetic method combined with theoretical calculations was successfully
      applied to probe the proton transfer reaction by proton-bound 2
      (sulfinylmethylene)pyridine/benzimidazole complexes in the fragmentation of
      protonated esomeprazole analogs by ESI CID MS, which is a strong evidence that
      the kinetic method can be applied in identifying a proton-bound dimeric
      intermediate in the fragmentation of protonated ions.

PMID- 24677527
TI  - Improved isobaric tandem mass tag quantification by ion mobility mass
      spectrometry.
AB  - RATIONALE: Isobaric tandem mass tags are an attractive alternative to mass
      difference tags and label-free approaches for quantitative proteomics due to the
      high degree of multiplexing that can be performed with their implementation. A
      drawback of tandem mass tags are that the co-isolation and co-fragmentation of
      labeled peptide precursors can result in chimeric tandem mass (MS/MS) spectra
      that can underestimate the fold-change expression of each peptide. Ion mobility
      (IM) separations coupled to quadrupole time-of-flight (Q-TOF) instruments have
      the potential to mitigate MS/MS spectra chimeracy since IM-MS has the ability to
      separate ions based on charge, m/z, and collision cross section (CCS). METHODS:
      Two complex protein mixtures, labeled with DiLeu isobaric tandem mass tags in
      opposite ratios, were mixed together and analyzed by data-dependent LC/IM-MS/MS.
      The accuracy of reporters from interfering pairs was compared with and without IM
      separation. RESULTS: IM separation was able to mitigate isobaric interference
      from differentially charged interfering ion pairs, as well as pairs of the same
      charge. Of the eight example precursors shown, only one had reporters that
      remained compressed below the significance threshold after IM separation.
      CONCLUSIONS: The results of this investigation demonstrate proof-of-principle
      that IM separation of tagged precursors prior to MS/MS fragmentation can help
      mitigate quantitative inaccuracies caused by isobaric interference. Future
      improvements of the method would include software for automated correction and
      use of higher resolution IM instrumentations.

PMID- 24677529
TI  - A first glimpse at the genome of the Baikalian amphipod Eulimnogammarus
      verrucosus.
AB  - Eulimnogammarus verrucosus is an amphipod endemic to the unique ecosystem of Lake
      Baikal and serves as an emerging model in ecotoxicological studies. We report
      here on a survey sequencing of its genome as a first step to establish sequence
      resources for this species. From a single lane of paired-end sequencing data, we
      estimated the genome size as nearly 10 Gb and we obtained an overview of the
      repeat content. At least two-thirds of the genome are non-unique DNA, and a third
      of the genomic DNA is composed of just five families of repetitive elements,
      including low-complexity sequences. Attempts to use off-the-shelf assembly tools
      failed on the available low-coverage data both before and after removal of highly
      repetitive components. Using a seed-based approach we nevertheless assembled
      short contigs covering 33 pre-microRNAs and the homeodomain-containing exon of
      nine Hox genes. The absence of clear evidence for paralogs implies that a genome
      duplication did not contribute to the large genome size. We furthermore report
      the assembly of the mitochondrial genome using a new, guided "crystallization"
      procedure. The initial results presented here set the stage for a more complete
      sequencing and analysis of this large genome.

PMID- 24677528
TI  - A simple strategy for glycosyltransferase-catalyzed aminosugar nucleotide
      synthesis.
AB  - A set of 2-chloro-4-nitrophenyl glucosamino-/xylosaminosides were synthesized and
      assessed as potential substrates in the context of glycosyltransferase-catalyzed
      formation of the corresponding UDP/TDP-alpha-D-glucosamino-/xylosaminosugars and
      in single-vessel model transglycosylation reactions. This study highlights a
      robust platform for aminosugar nucleotide synthesis and reveals OleD Loki to be a
      proficient catalyst for U/TDP-aminosugar synthesis and utilization

PMID- 24677531
TI  - Lake eutrophication and its implications for organic carbon sequestration in
      Europe.
AB  - The eutrophication of lowland lakes in Europe by excess nitrogen (N) and
      phosphorus (P) is severe because of the long history of land-cover change and
      agricultural intensification. The ecological and socio-economic effects of
      eutrophication are well understood but its effect on organic carbon (OC)
      sequestration by lakes and its change overtime has not been determined. Here, we
      compile data from ~90 culturally impacted European lakes [~60% are eutrophic,
      Total P (TP) >30 MUg P l(-1) ] and determine the extent to which OC burial rates
      have increased over the past 100-150 years. The average focussing corrected, OC
      accumulation rate (C ARFC ) for the period 1950-1990 was ~60 g C m(-2) yr(-1) ,
      and for lakes with >100 MUg TP l(-1) the average was ~100 g C m(-2) yr(-1) . The
      ratio of post-1950 to 1900-1950 C AR is low (~1.5) indicating that C accumulation
      rates have been high throughout the 20th century. Compared to background
      estimates of OC burial (~5-10 g C m(-2) yr(-1) ), contemporary rates have
      increased by at least four to fivefold. The statistical relationship between C
      ARFC and TP derived from this study (r(2) = 0.5) can be used to estimate OC
      burial at sites lacking estimates of sediment C-burial. The implications of
      eutrophication, diagenesis, lake morphometry and sediment focussing as controls
      of OC burial rates are considered. A conservative interpretation of the results
      of the this study suggests that lowland European meso- to eutrophic lakes with
      >30 MUg TP l(-1) had OC burial rates in excess of 50 g C m(-2) yr(-1) over the
      past century, indicating that previous estimates of regional lake OC burial have
      seriously underestimated their contribution to European carbon sequestration.
      Enhanced OC burial by lakes is one positive side-effect of the otherwise negative
      impact of the anthropogenic disruption of nutrient cycles.

PMID- 24677532
TI  - Critical size defect regeneration by rhPTH-collagen membrane as a new tissue
      engineering tool.
AB  - Recombinant Human Parathyroid Hormone (rhPTH 1-34) administration is an effective
      treatment to improve bone mass in osteoporosis. The aim of this study was to
      develop a Tissue Engeenering Tool for bone regeneration. We evaluated the
      efficacy of a freeze dried rhPTH membrane in calvarial critical size defect
      (CSD). Forty-four Wistar female rats (body weight 150 +/- 50 g) with CSD (5 mm)
      were divided into four groups: group 1: rhPTH membrane (rhPTHm); group 2:
      atelocollagen membrane (Cm); group 3: rhPTH and atelocollagen I (CrhPTHm); group
      4: without any treatment (CG). All samples were evaluated on the 1st, 3rd, and
      6th weeks (weeks) post-surgery by soft X-ray, histological and histometric
      studies. Soft X-ray results showed a radiolucent image with many irregular
      radiopaque areas. Histologically, rhPTHm was replaced by reticular bone (7%)
      since 3rd week, and lamellar bone ossicles (30%) at 6th week. Cm showed bone
      formation like composite bone type on week 1st, 3rd, and 6th (2%, 44%, and 41%,
      respectively). With CrhPTHm, bone formation was observed in all periods (2.4%,
      48%, and 53%), showing statistical difference with CG in the 3rd and 6th wks (p =
      0.03 and 0.01). Our results demonstrated the effectiveness of a new biomaterial
      called CrhPTHm because its ability to regenerate calvarial CSD. Moreover, the
      membrane represents a new local intermittent delivery system allowing rhPTH slow
      release.

PMID- 24677530
TI  - Repetition suppression of face-selective evoked and induced EEG recorded from
      human cortex.
AB  - In functional MRI studies, repetition suppression refers to the reduction of
      hemodynamic activation to repeated stimulus presentation. For example, the
      repeated presentation of a face reduces the hemodynamic response evoked by faces
      in the fusiform gyrus. The neural events that underlie repetition suppression are
      not well understood. Indeed, in contrast to the hemodynamic response, the face
      specific N200 recorded from subdural electrodes on the ventral occipitotemporal
      cortex, primarily along the fusiform gyrus, has been reported to be insensitive
      to face-identity repetition. We have previously described a face-specific
      broadband gamma (30-100 Hz) response at ventral face-specific N200 sites that is
      functionally dissociable from the N200. In this study, we investigate whether
      gamma and other components of the electroencephalogram spectrum are affected by
      face-identity repetition independently of the N200. Participants viewed
      sequentially presented identical faces. At sites on and around the fusiform
      gyrus, we found that face repetition modulated alpha (8-12 Hz), low-gamma (30-60
      Hz), and high-gamma (60-100 Hz) synchrony, but not the N200. These findings
      provide evidence of a spatially co-localized progression of face processing.
      Whereas the N200 reflects an initial obligatory response that is less sensitive
      to face-identity repetition, the subsequent spectral fluctuations reflect more
      elaborative face processing and are thus sensitive to face novelty. It is notable
      that the observed modulations were different for different frequency bands. We
      observed repetition suppression of broadband gamma, but repetition enhancement of
      alpha synchrony. This difference is discussed with regard to an existing model of
      repetition suppression and behavioral repetition priming.

PMID- 24677533
TI  - Energy storing electrical cables: integrating energy storage and electrical
      conduction.

PMID- 24677534
TI  - Experiences of self-practice/self-reflection in cognitive behavioural therapy: a
      meta-synthesis of qualitative studies.
AB  - BACKGROUND: Self-practice/self-reflection is a valuable training strategy which
      involves therapists applying therapeutic techniques to themselves, and reflecting
      on the process. PURPOSE: To undertake a meta-synthesis of qualitative studies
      exploring therapists' experiences of self-practice/self-reflection in cognitive
      behavioural therapy (CBT). This would integrate, and interpret, the current
      literature in order to develop a new understanding, and contribute to the
      development of CBT training programmes. METHODS: The meta-synthesis encompassed
      three distinct phases: undertaking a comprehensive and systematic literature
      search; critically appraising the papers; and synthesising the data using the
      meta-ethnographic method. RESULTS: The literature search identified 378 papers,
      ten met the criteria for inclusion. After critical appraisal, all were included
      in the synthesis. The synthesis identified 14 constructs, which fell into three
      broad categories: 'experience of self-practice/self-reflection'; 'outcomes of
      self-practice/self-reflection'; and 'implications for training'. This synthesis
      found that self-practice allows therapists to put themselves into their clients'
      shoes, experiencing the benefits that therapy can bring but also the problems
      that clients can run in to. This experience increases therapists' empathy for
      their clients, allowing them to draw on their own experiences in therapy. As a
      result, therapists tend to feel both more confident in themselves and more
      competent as a therapist. The self-practice/self-reflection process was
      facilitated by reflective writing and working with others, particularly peers.
      CONCLUSIONS: Self-practice/self-reflection is a valuable training strategy in
      CBT, which has a range of beneficial outcomes. It can also be used as a means of
      continuing personal and professional development. PRACTITIONER POINTS: Self
      practice of CBT techniques, and reflecting on the process, can be a useful
      training strategy and helpful for ongoing development Therapists could consider
      developing a 'self-case' study, rather than using the exercises as one-off
      techniques, recording reflections in writing, and sharing reflections with peers.
      Self-practice/self-reflection can be particularly helpful for increasing empathy
      for clients, highlighting the difficulties they may encounter.

PMID- 24677535
TI  - What is the threshold for a clinically relevant effect? The case of major
      depressive disorders.
AB  - BACKGROUND: Randomized trials can show whether a treatment effect is
      statistically significant and can describe the size of the effect. There are,
      however, no validated methods available for establishing the clinical relevance
      of these outcomes. Recently, it was proposed that a standardized mean difference
      (SMD) of 0.50 be used as cutoff for clinical relevance in the treatment of
      depression. METHODS: We explore what the effect size means and why the size of an
      effect has little bearing on its clinical relevance. We will also examine how the
      "minimally important difference," as seen from the patient perspective, may be
      helpful in deciding where the cutoff for clinical relevance should be placed for
      a given condition. RESULTS: Effect sizes in itself cannot give an indication of
      the clinical relevance of an intervention because the outcome itself determines
      the clinical relevance and not only the size of the effects. The "minimal
      important difference" (MID) could be used as a starting point for pinpointing the
      cutoff for clinical relevance. A first, rough attempt to implement this approach
      for depression resulted in a tentative clinical relevance cutoff of SMD = 0.24.
      Using this cutoff, psychotherapy, pharmacotherapy, and combined treatment have
      effect sizes above this cutoff. DISCUSSION: Statistical outcomes cannot be
      equated with clinical relevance. The "MID" may be used for pinpointing the cutoff
      for clinical relevance, but more work in this area is needed.

PMID- 24677536
TI  - Nanostructured anti-bacterial poly-lactic-co-glycolic acid films for skin tissue
      engineering applications.
AB  - Major issues faced with the use of today's skin grafts are infection, scar tissue
      formation, insufficient keratinocyte (or skin producing cells) proliferation and
      high production costs. To overcome these limitations, we propose here for the
      first time, a nanofeatured poly(lactide-co-glycolide) (PLGA) membrane as a next
      generation antibacterial skin graft material. An alkaline surface treatment
      method was used to create random nanofeatures on PLGA membranes where sodium
      hydroxide (NaOH) concentration and exposure times were altered to control surface
      morphology. Most significantly, and without the use of antibiotics, results
      showed a decrease in Staphylococcus aureus (a dangerous pathogen infecting skin
      grafts) growth for up to ~40% after 2 days of culture on nanofeatured PLGA
      membranes compared to untreated controls. Results also showed that while bacteria
      growth was stunted, mammalian cell growth was not. Specifically, cell culture
      results showed an increase in human epidermal keratinocyte density, while the
      density of scar tissue forming human dermal fibroblasts, did not change on
      nanofeatured PLGA surfaces compared to the untreated controls after 3 days of
      culture. These findings indicate that the alkaline treatment of PLGA membranes is
      a promising quick and effective manner to limit scar tissue formation and
      bacterial invasion while increasing skin cell proliferation for improving
      numerous wound-healing applications.

PMID- 24677537
TI  - Palladium-catalyzed C-S activation/aryne insertion/coupling sequence: synthesis
      of functionalized 2-quinolinones.
AB  - The insertion of an aryne into a C-S bond can suppress the addition of an S
      nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)2, a
      wide range of alpha-carbamoyl ketene dithioacetals readily react with arynes to
      selectively afford functionalized 2-quinolinones in high yields under neutral
      reaction conditions by a C-S activation/aryne insertion/intramolecular coupling
      sequence. The attractive feature of the new strategy also lies in the versatile
      transformations of the alkythio-substituted quinolinone products.

PMID- 24677538
TI  - AERS spider: an online interactive tool to mine statistical associations in
      Adverse Event Reporting System.
AB  - BACKGROUND: Exploration of the Adverse Event Reporting System (AERS) data by a
      wide scientific community is limited due to several factors. First, AERS data
      must be intensively preprocessed to be converted into analyzable format. Second,
      application of the currently accepted disproportional reporting measures results
      in false positive signals. METHODS: We proposed a data mining strategy to improve
      hypothesis generation with respect to potential associations. RESULTS: By
      numerous examples, we illustrate that our strategy controls the false positive
      signals. We implemented a free online tool, AERS spider
      (www.chemoprofiling.org/AERS). CONCLUSIONS: We believe that AERS spider would be
      a valuable tool for drug safety experts.

PMID- 24677540
TI  - Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal
      for defining this disorder.
AB  - The existence of spontaneous heparin-induced thrombocytopenia (HIT) syndrome (or
      autoimmune HIT), defined as a transient prothrombotic thrombocytopenic disorder
      without proximate heparin exposure serologically indistinguishable from HIT, is
      controversial. We describe 2 new cases presenting with thrombotic
      stroke/thrombocytopenia: one following shoulder hemi-arthroplasty (performed
      without heparin) and the other presenting to the emergency room without prior
      hospitalization, heparin exposure, or preceding infection. Both patients tested
      strongly positive for anti-platelet factor 4 (PF4)/heparin immunoglobulin (Ig)G
      in 2 different immunoassays and in the platelet serotonin-release assay.
      Crucially, both patients' sera also caused strong (>80%) serotonin release in the
      absence of heparin, a serologic feature characteristic of delayed-onset HIT (ie,
      where heparin use precedes HIT but is not required for subsequent development or
      worsening of thrombocytopenia). We propose that a rigorous definition of
      spontaneous HIT syndrome should include otherwise unexplained
      thrombocytopenia/thrombosis without proximate heparin exposure and with anti
      PF4/heparin IgG antibodies that cause strong in vitro platelet activation even in
      the absence of heparin. 

PMID- 24677539
TI  - Runx1 and Cbfbeta regulate the development of Flt3+ dendritic cell progenitors
      and restrict myeloproliferative disorder.
AB  - Runx1 and Cbfbeta are critical for the establishment of definitive hematopoiesis
      and are implicated in leukemic transformation. Despite the absolute requirements
      for these factors in the development of hematopoietic stem cells and lymphocytes,
      their roles in the development of bone marrow progenitor subsets have not been
      defined. Here, we demonstrate that Cbfbeta is essential for the development of
      Flt3(+) macrophage-dendritic cell (DC) progenitors in the bone marrow and all DC
      subsets in the periphery. Besides the loss of DC progenitors, pan-hematopoietic
      Cbfb-deficient mice also lack CD105(+) erythroid progenitors, leading to severe
      anemia at 3 to 4 months of age. Instead, Cbfb deficiency results in aberrant
      progenitor differentiation toward granulocyte-macrophage progenitors (GMPs),
      resulting in a myeloproliferative phenotype with accumulation of GMPs in the
      periphery and cellular infiltration of the liver. Expression of the transcription
      factor Irf8 is severely reduced in Cbfb-deficient progenitors, and overexpression
      of Irf8 restors DC differentiation. These results demonstrate that Runx proteins
      and Cbfbeta restrict granulocyte lineage commitment to facilitate multilineage
      hematopoietic differentiation and thus identify their novel tumor suppressor
      function in myeloid leukemia. 

PMID- 24677541
TI  - Platelet bioenergetic screen in sickle cell patients reveals mitochondrial
      complex V inhibition, which contributes to platelet activation.
AB  - Bioenergetic dysfunction, although central to the pathogenesis of numerous
      diseases, remains uncharacterized in many patient populations because of the
      invasiveness of obtaining tissue for mitochondrial studies. Although platelets
      are an accessible source of mitochondria, the role of bioenergetics in regulating
      platelet function remains unclear. Herein, we validate extracellular flux
      analysis in human platelets and use this technique to screen for mitochondrial
      dysfunction in sickle cell disease (SCD) patients, a population with aberrant
      platelet activation of an unknown mechanism and in which mitochondrial function
      has never been assessed. We identify a bioenergetic alteration in SCD patients
      characterized by deficient complex V activity, leading to decreased mitochondrial
      respiration, membrane hyperpolarization, and augmented oxidant production
      compared with healthy subjects. This dysfunction correlates with platelet
      activation and hemolysis in vivo and can be recapitulated in vitro by exposing
      healthy platelets to hemoglobin or a complex V inhibitor. Further, reproduction
      of this dysfunction in vitro activates healthy platelets, an effect prevented by
      attenuation of mitochondrial hyperpolarization or by scavenging mitochondrial
      oxidants. These data identify bioenergetic dysfunction in SCD patients for the
      first time and establish mitochondrial hyperpolarization and oxidant generation
      as potential pathogenic mechanism in SCD as well as a modulator of healthy
      platelet function. 

PMID- 24677542
TI  - A new human mast cell line expressing a functional IgE receptor converts to
      tumorigenic growth by KIT D816V transfection.
AB  - In systemic mastocytosis (SM), clinical problems arise from factor-independent
      proliferation of mast cells (MCs) and the increased release of mediators by MCs,
      but no human cell line model for studying MC activation in the context of SM is
      available. We have created a stable stem cell factor (SCF) -dependent human MC
      line, ROSA(KIT WT), expressing a fully functional immunoglobulin E (IgE)
      receptor. Transfection with KIT D816V converted ROSA(KIT WT) cells into an SCF
      independent clone, ROSA(KIT D816V), which produced a mastocytosis-like disease in
      NSG mice. Although several signaling pathways were activated, ROSA(KIT D816V) did
      not exhibit an increased, but did exhibit a decreased responsiveness to IgE
      dependent stimuli. Moreover, NSG mice bearing ROSA(KIT D816V)-derived tumors did
      not show mediator-related symptoms, and KIT D816V-positive MCs obtained from
      patients with SM did not show increased IgE-dependent histamine release or CD63
      upregulation. Our data show that KIT D816V is a disease-propagating oncoprotein,
      but it does not activate MCs to release proinflammatory mediators, which may
      explain why mediator-related symptoms in SM occur preferentially in the context
      of a coexisting allergy. ROSA(KIT D816V) may provide a valuable tool for studying
      the pathogenesis of mastocytosis and should facilitate the development of novel
      drugs for treating SM patients. 

PMID- 24677543
TI  - Human t(14;18)positive germinal center B cells: a new step in follicular lymphoma
      pathogenesis?
AB  - Follicular lymphoma (FL) is a B-cell neoplasm resulting from the transformation
      of germinal center (GC) B cells. Although t(14;18) and ectopic B-cell lymphoma 2
      (BCL2) expression constitute the genetic hallmark of FL, t(14;18)(pos) B cells
      bearing genotypic and phenotypic features of FL cells can be found in the blood
      of most healthy individuals. Nevertheless, the localization of these FL-like
      cells (FLLCs) in nonmalignant GC-rich tissues and the functional consequences of
      BCL2 overexpression have not been evaluated thus far. Among 85 reactive lymph
      node (RLN) samples, 14% were found to contain high levels of t(14;18) by
      quantitative polymerase chain reaction. In t(14;18)(hi) RLNs,
      CD20(pos)BCL2(pos)CD10(pos) FLLCs consistently accumulated within the GC,
      essentially as nonproliferative CXCR4(neg) centrocytes. Moreover, they displayed
      a reduced response to proliferative stimuli in vitro. Altogether, our findings
      provide new insights into in situ FLLC functional properties and suggest that
      these cells have not acquired the ultimate genetic events leading to FL
      transformation. 

PMID- 24677544
TI  - c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their
      susceptibility to NK-mediated lysis.
AB  - Cytarabine (cytosine arabinoside) is one of the most effective drugs for the
      treatment of patients diagnosed with acute myeloid leukemia (AML). Despite its
      efficiency against AML cells, the emergence of drug resistance due to prolonged
      chemotherapy in most patients is still a major obstacle. Several studies have
      shown that drug resistance mechanisms alter the sensitivity of leukemia cells to
      immune system effector cells. To investigate this phenomenon, parental acute
      myeloid cell lines, HL-60 and KG-1, were continuously exposed to increasing doses
      of cytarabine in order to establish equivalent resistant cell lines, HL-60(R) and
      KG-1(R). Our data indicate that cytarabine-resistant cells are more susceptible
      to natural killer (NK)-mediated cell lysis as compared with parental cytarabine
      sensitive cells. The increased susceptibility correlates with the induction of UL
      16 binding proteins (ULBP) 1/2/3 and NK group 2, member D (NKG2D) ligands on
      target cells by a mechanism involving c-Myc induction. More importantly,
      chromatin immunoprecipitation assay revealed that ULBP1/3 are direct targets of c
      Myc. Using drug-resistant primary AML blasts as target cells, inhibition of c-Myc
      resulted in decreased expression of NKG2D ligands and the subsequent impairment
      of NK cell lysis. This study provides for the first time, the c-Myc dependent
      regulation of NKG2D ligands in AML. 

PMID- 24677546
TI  - Highly luminescent colloidal Eu(3)+-doped KZnF(3) nanoparticles for the selective
      and sensitive detection of Cu(II) ions.
AB  - This article describes a green synthetic approach to prepare water dispersible
      perovskite-type Eu3+-doped KZnF3 nanoparticles, carried out using environmentally
      friendly microwave irradiation at low temperature (85 8C) with water as a
      solvent. Incorporation of Eu3+ ions into the KZnF3 matrix is confirmed by strong
      red emission upon ultraviolet (UV) excitation of the nanoparticles. The
      nanoparticles are coated with poly(acrylic acid) (PAA), which enhances the
      dispersibility of the nanoparticles in hydrophilic solvents. The strong red
      emission from Eu3+ ions is selectively quenched upon addition of CuII ions, thus
      making the nanoparticles a potential CuII sensing material. This sensing ability
      is highly reversible by the addition of ethylenediaminetetraacetic acid (EDTA),
      with recovery of almost 90% of the luminescence. If the nanoparticles are
      strongly attached to a positively charged surface, dipping the surface in a CuII
      solution leads to the quenching of Eu3+ luminescence, which can be recovered
      after dipping in an EDTA solution. This process can be repeated for more than
      five cycles with only a slight decrease in the sensing ability. In addition to
      sensing, the strong luminescence from Eu3+-doped KZnF3 nanoparticles could be
      used as a tool for bioimaging.

PMID- 24677545
TI  - Migration of sea urchin primordial germ cells.
AB  - BACKGROUND: Small micromeres are produced at the fifth cleavage of sea urchin
      development. They express markers of primordial germ cells (PGCs), and are
      required for the production of gametes. In most animals, PGCs migrate from sites
      of formation to the somatic gonad. Here, we investigated whether they also
      exhibit similar migratory behaviors using live-cell imaging of small micromere
      plasma membranes. RESULTS: Early in gastrulation, small micromeres transition
      from non-motile epithelial cells, to motile quasi-mesenchymal cells. Late in
      gastrulation, at 43 hr post fertilization (HPF), they are embedded in the tip of
      the archenteron, but remain motile. From 43-49 HPF, they project numerous
      cortical blebs into the blastocoel, and filopodia that contact ectoderm. By 54
      HPF, they begin moving in the plane of the blastoderm, often in a directed
      fashion, towards the coelomic pouches. Isolated small micromeres also produced
      blebs and filopodia. CONCLUSIONS: Previous work suggested that passive
      translocation governs some of the movement of small micromeres during
      gastrulation. Here we show that small micromeres are motile cells that can
      traverse the archenteron, change position along the left-right axis, and migrate
      to coelomic pouches. These motility mechanisms are likely to play an important
      role in their left-right segregation.

PMID- 24677547
TI  - On the use of metal purine derivatives (M=Ir, Rh) for the selective labeling of
      nucleosides and nucleotides.
AB  - The reactions of neutral or cationic IrIII and RhIII derivatives of phenyl purine
      nucleobases with unsymmetrical alkynes produce new metallacycles in a predictable
      manner, which allows for the incorporation of either photoactive (anthracene or
      pyrene) or electroactive (ferrocene) labels in the nucleotide or nucleoside
      moiety. The reported methodology (metalation of the purine derivative and
      subsequent marker insertion) could be used for the postfunctionalization and
      unambiguous labeling of oligonucleotides.

PMID- 24677548
TI  - Cationic Ir/Me-BIPAM-catalyzed asymmetric intramolecular direct hydroarylation of
      alpha-ketoamides.
AB  - Asymmetric intramolecular direct hydroarylation of alpha-ketoamides gives various
      types of optically active 3-substituted 3-hydroxy-2-oxindoles in high yields with
      complete regioselectivity and high enantioselectivities (84-98% ee). This is
      realized by the use of the cationic iridium complex [Ir(cod)2](BAr(F)4) and the
      chiral O-linked bidentate phosphoramidite (R,R)-Me-BIPAM.

PMID- 24677549
TI  - Clinical evidence for a mandibular to maxillary transformation in
      Auriculocondylar syndrome.

PMID- 24677550
TI  - GSK3beta regulates oligodendrogenesis in the dorsal microdomain of the
      subventricular zone via Wnt-beta-catenin signaling.
AB  - Oligodendrocytes, the myelinating cells of the CNS, are derived postnatally from
      oligodendrocyte precursors (OPs) of the subventricular zone (SVZ). However, the
      mechanisms that regulate their generation from SVZ neural stem cells (NSC) are
      poorly understood. Here, we have examined the role of glycogen synthase kinase
      3beta (GSK3beta), an effector of multiple converging signaling pathways in
      postnatal mice. The expression of GSK3beta by rt-qPCR was most prominent in the
      SVZ and in the developing white matter, around the first 1-2 weeks of postnatal
      life, coinciding with the peak periods of OP differentiation. Intraventricular
      infusion of the GSK3beta inhibitor ARA-014418 in mice aged postnatal day (P) 8-11
      significantly increased generation of OPs in the dorsal microdomain of the SVZ,
      as shown by expression of cell specific markers using rt-qPCR and
      immunolabelling. Analysis of stage specific markers revealed that the
      augmentation of OPs occurred via increased specification from earlier SVZ cell
      types. These effects of GSK3beta inhibition on the dorsal SVZ were largely
      attributable to stimulation of the canonical Wnt/beta-catenin signaling pathway
      over other pathways. The results indicate GSK3beta is a key endogenous factor for
      specifically regulating oligodendrogenesis from the dorsal SVZ microdomain under
      the control of Wnt-signaling.

PMID- 24677551
TI  - Spatioselective growth of metal-organic framework nanocrystals on compositionally
      anisotropic polymer particles.
AB  - Selective growth of metal organic framework materials on the surface of
      compartmentalized polymer microparticles is achieved by electro-hydrodynamic co
      jetting, selective surface modification, and anisotropic crystal growth. 

PMID- 24677552
TI  - The Neurobiological Basis of the Distress Thermometer: A PET Study in Cancer
      Patients.
AB  - The objective of this study was to investigate the possible associations between
      the Distress Thermometer (DT) scores and the brain metabolism of structures
      involved in stress response. Twenty-one cancer patients were assessed using the
      DT, Problem Checklist and Hospital Anxiety and Depression Scale (HADS). The
      psychological measures were correlated with [18 F]PET-FDG brain glucose
      metabolism. Multiple and linear regression and binary logistic regression were
      run to analyse data. The DT and HADS scores illustrated that 48% of patients were
      distressed, 19% were depressed and 48% were anxious. Results showed that some
      subcortical areas activity, such as part of midbrain and of hypothalamus, was
      correlated with the DT scores. The Problem Checklist scores correlated with the
      activity of the same areas and included more regions in the limbic forebrain and
      brainstem. Compared with the DT and Problem Checklist, HADS-Depression scores
      showed a more extensive pattern of correlation with brain activity, including
      limbic and cortical areas. The results highlighted that the DT scores correlated
      with the activity of brain areas typically involved in stress response. Indeed,
      hypothalamus metabolism was found to be the best predictor of distressed
      patients.

PMID- 24677553
TI  - Utilization of small changes in serum creatinine with clinical risk factors to
      assess the risk of AKI in critically lll adults.
AB  - BACKGROUND AND OBJECTIVES: Disease biomarkers require appropriate clinical
      context to be used effectively. Combining clinical risk factors, in addition to
      small changes in serum creatinine, has been proposed to improve the assessment of
      AKI. This notion was developed in order to identify the risk of AKI early in a
      patient's clinical course. We set out to assess the performance of this
      combination approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A secondary
      analysis of data from a prospective multicenter intensive care unit cohort study
      (September 2009 to April 2010) was performed. Patients at high risk using this
      combination approach were defined as an early increase in serum creatinine of 0.1
      0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was
      defined and staged using the Acute Kidney Injury Network criteria. The primary
      outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3)
      within 7 days in the intensive care unit. RESULTS: Of 506 patients, 214 (42.2%)
      patients had early creatinine elevation and were deemed at high risk for AKI.
      This group was more likely to subsequently develop the primary endpoint (16.4%
      versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for
      severe AKI was 92%, the specificity was 62%, the positive predictive value was
      16%, and the negative predictive value was 99%. After adjustment for Sequential
      Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early
      creatinine elevation remained an independent predictor for severe AKI (adjusted
      relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early
      creatinine elevation to the best clinical model improved prediction of the
      primary outcome (area under the receiver operating characteristic curve increased
      from 0.75 to 0.83, P<0.001). CONCLUSION: Critically ill patients at high AKI
      risk, based on the combination of clinical factors and early creatinine
      elevation, are significantly more likely to develop severe AKI. As initially
      hypothesized, the high-risk combination group methodology can be used to identify
      patients at low risk for severe AKI in whom AKI biomarker testing may be expected
      to have low yield. The high risk combination group methodology could potentially
      allow clinicians to optimize biomarker use.

PMID- 24677554
TI  - Incorporation of biomarkers with the renal angina index for prediction of severe
      AKI in critically ill children.
AB  - BACKGROUND AND OBJECTIVES: Novel AKI biomarkers carry variable performance for
      prediction of AKI in patients with heterogeneous illness. Until utility is
      demonstrated in critically ill patients outside of the cardiopulmonary bypass
      population, AKI biomarkers are unlikely to gain widespread implementation.
      Operationalization of an AKI risk stratification methodology, termed renal
      angina, was recently reported to enhance prediction at the time of intensive care
      unit admission for persistent severe AKI. The renal angina index (RAI) was
      developed to provide the clinical context to direct AKI biomarker testing. This
      study tested the hypothesis that incorporation of AKI biomarkers in patients
      fulfilling renal angina improves the prediction of persistent severe AKI. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: In a multicenter study of 214 patients
      admitted to the pediatric intensive care unit with sepsis, the discrimination of
      plasma neutrophil gelatinase-associated lipocalin (NGAL), matrix
      metalloproteinase-8 (MMP-8), and neutrophil elastase-2 (Ela-2) were determined
      individually and in combination with the RAI for severe AKI. Net reclassification
      improvement (NRI) and integrated discrimination improvement (IDI) were
      calculated. RESULTS: Individual biomarkers demonstrated marginal discrimination
      for severe AKI (area under curve [AUC]: NGAL, 0.72; MMP-8, 0.68; Ela-2, 0.72),
      inferior to prediction by the clinical model of the RAI (AUC=0.80). Incorporation
      of each biomarker significantly added to the renal angina model AKI prediction
      (AUC=0.80, increased to 0.84-0.88; P<0.05 for each). The inclusion of each
      biomarker with the RAI demonstrated NRI (0.512, 0.428, and 0.545 for NGAL, MMP-8,
      and Ela-2, respectively; all P<0.03) and IDI (0.075 for Ela-2). The inclusion of
      both Ela-2 and NGAL with RAI demonstrated an NRI of 0.871 (P<0.001) and an IDI of
      0.1 (P=0.01). CONCLUSIONS: This study shows that incorporation of AKI biomarkers
      into the RAI improves discrimination for severe AKI. The RAI optimizes the
      utility of AKI biomarkers in a heterogeneous, critically ill patient population.

PMID- 24677555
TI  - Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients
      with CKD stages 2-4.
AB  - BACKGROUND AND OBJECTIVES: CKD-mineral and bone disorders (CKD-MBD) measures
      contribute to cardiovascular morbidity in patients with CKD. Among these,
      fibroblast growth factor (FGF)-23 and its coreceptor Klotho may exert direct
      effects on vascular and myocardial tissues. Klotho exists in a membrane-bound and
      a soluble form (sKlotho). Recent experimental evidence suggests sKlotho has
      vasculoprotective functions. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS:
      Traditional and novel CKD-MBD variables were measured among 444 patients with CKD
      stages 2-4 recruited between September 2008 and November 2012 into the ongoing
      CARE FOR HOMe study. Across tertiles of baseline sKlotho and FGF-23, the
      incidence of two distinct combined end points was analyzed: (1) the first
      occurrence of an atherosclerotic event or death from any cause and (2) the time
      until hospital admission for decompensated heart failure or death from any cause.
      RESULTS: Patients were followed for 2.6 (interquartile range, 1.4-3.6) years.
      sKlotho tertiles predicted neither atherosclerotic events/death (fully adjusted
      Cox regression analysis: hazard ratio [HR] for third versus first sKlotho
      tertile, 0.75 [95% confidence interval (95% CI), 0.43-1.30]; P=0.30) nor the
      occurrence of decompensated heart failure/death (HR for third versus first
      sKlotho tertile, 0.81 [95% CI, 0.39-1.66]; P=0.56). In contrast, patients in the
      highest FGF-23 tertile had higher risk for both end points in univariate
      analysis. Adjustment for kidney function attenuated the association between FGF
      23 and atherosclerotic events/death (HR for third versus first FGF-23 tertile,
      1.23 [95% CI, 0.58-2.61]; P=0.59), whereas the association between FGF-23 and
      decompensated heart failure/death remained significant after adjustment for
      confounders (HR for third versus first FGF-23 tertile, 4.51 [95% CI, 1.33-15.21];
      P=0.02). CONCLUSIONS: In this prospective observational study of limited sample
      size, sKlotho was not significantly related to cardiovascular outcomes. FGF-23
      was significantly associated with future decompensated heart failure but not
      incident atherosclerotic events.

PMID- 24677556
TI  - Renal angina: right concept...Wrong name?

PMID- 24677557
TI  - Epidemiology and outcomes in community-acquired versus hospital-acquired AKI.
AB  - BACKGROUND AND OBJECTIVE: Compared with AKI in hospitalized patients, little is
      known about patients sustaining AKI in the community and how this differs from
      AKI in hospital. This study compared epidemiology, risk factors, and short- and
      long-term outcomes for patients with community-acquired (CA) and hospital
      acquired (HA) AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of
      15,976 patients admitted to two district general hospitals between July 11, 2011,
      and January 15, 2012 were studied. Through use of an electronic database and the
      AKI Network classification, 686 patients with CA-AKI and 334 patients with HA-AKI
      were identified. Patients were followed up for 14 months, and data were collated
      on short-term and long-term renal and patient outcomes. RESULTS: The incidence of
      CA-AKI among all hospital admissions was 4.3% compared with an incidence of 2.1%
      of HA-AKI, giving an overall AKI incidence of 6.4%. Patients with CA-AKI were
      younger than patients with HA-AKI. Risks for developing HA and CA-AKI were
      similar and included preexisting CKD, cardiac failure, ischemic heart disease,
      hypertension, diabetes, dementia, and cancer. Patients with CA-AKI were more
      likely to have stage 3 AKI and had shorter lengths of hospital stay than patients
      with HA-AKI. Those with CA-AKI had better (multivariate-adjusted) survival than
      patients with HA-AKI (hazard ratio, 1.8 [95% CI, 1.44-2.13; P<0.001] for HA-AKI
      group). Mortality for the CA-AKI group was 45%; 43.7% of these deaths were acute
      in-hospital deaths. Mortality for the HA-AKI group was 62.9%, with 68.1% of these
      deaths being acute in-hospital deaths. Renal referral rates were low across the
      cohorts (8.3%). Renal outcomes were similar in both CA-AKI and HA-AKI groups,
      with 39.4% and 33.6% of patients in both groups developing de novo CKD or
      progression of preexisting CKD within 14 months, respectively. CONCLUSION:
      Patients with CA-AKI sustain more severe AKI than patients with HA-AKI. Despite
      having risk factors similar to those of patients with HA-AKI, patients with CA
      AKI have better short- and long-term outcomes.

PMID- 24677558
TI  - Insulin resistance in CKD.

PMID- 24677559
TI  - Associations between depressive symptoms and incident ESRD in a diabetic cohort.
AB  - BACKGROUND AND OBJECTIVES: Comorbid major depression is associated with adverse
      health outcomes in patients with diabetes, but little is known regarding its
      associations with long-term renal outcomes in this population. Furthermore, the
      impact of minor depression on renal outcomes is not known. This study evaluated
      associations between depressive symptoms and risk of incident ESRD in a diabetic
      cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective,
      observational cohort study, 3886 ambulatory adults with diabetes were recruited
      from primary care clinics of a large health maintenance organization in the state
      of Washington. Demographics, laboratory data, depressive symptoms (based on the
      Patient Health Questionnaire-9), and patterns of diabetes self-care were
      collected. Participants were considered depressed if they had the required number
      of depressive symptoms (>= 5 for major or 2-4 for minor depressive symptoms),
      including depressed mood or anhedonia, >50% of the time for >= 2 weeks and a
      Patient Health Questionnaire-9 score >= 10 for major and >= 5 for minor
      depressive symptoms. Risk of incident ESRD was estimated using Cox proportional
      hazards regression, with predialysis death as a competing risk. RESULTS: During a
      median follow-up of 8.8 years, 87 patients (2.2%) developed ESRD. Major
      depressive symptoms were associated with a higher risk of incident ESRD (hazard
      ratio, 1.85; 95% confidence interval, 1.02 to 3.33) after adjusting for age, sex,
      race/ethnicity, marital status, education, smoking, body mass index, diabetes
      duration, hemoglobin A1c, baseline kidney function, microalbuminuria,
      hypertension, renin-angiotensin system blockers, and adherence to diabetes self
      care. Minor depressive symptoms were not significantly associated with incident
      ESRD (hazard ratio, 1.08; 95% confidence interval, 0.52 to 2.25). CONCLUSION:
      Major depressive symptoms, but not minor depressive symptoms, were associated
      with a higher risk of incident ESRD over 10 years. Additional studies are needed
      to determine whether treatment for depression can improve renal outcomes in
      patients with diabetes.

PMID- 24677560
TI  - Peritoneal dialysis-related peritonitis due to coagulase-negative Staphylococcus:
      a review of 115 cases in a Brazilian center.
AB  - BACKGROUND AND OBJECTIVES: Coagulase-negative Staphylococcus (CNS) is the most
      frequent cause of peritoneal dialysis (PD)-related peritonitis in many centers.
      This study aimed to describe clinical and microbiologic characteristics of 115
      CNS episodes and to determine factors influencing the outcome. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This study reviewed the records of 115 CNS
      peritonitis episodes that occurred in 74 patients between 1994 and 2011 at a
      single university center. Peritonitis incidences were calculated for three
      consecutive 6-year periods (P1, 1994-1999; P2, 2000-2005; P3, 2006-2011) and
      annually. The production of biofilms, enzymes, and toxins was evaluated.
      Oxacillin resistance was evaluated based on its minimum inhibitory concentration
      and the presence of the mecA gene. RESULTS: The overall incidence of CNS
      peritonitis was 0.15 episodes per patient per year and did not vary over time
      (0.12, 0.14, and 0.16 for P1, P2, and P3, respectively; P=0.21). The oxacillin
      resistance rate was 69.6%. Toxin and enzyme production was infrequent and 36.5%
      of CNS strains presented the gene encoding biofilm production. The presence of
      icaAD genes associated with biofilm production was predictive of relapses or
      repeat episodes (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to
      7.19; P=0.03). Overall, 70 episodes (60.9%) resolved; oxacillin susceptibility
      (OR, 4.41; 95% CI, 1.48 to 13.17; P=0.01) and vancomycin use as the first
      treatment (OR, 22.27; 95% CI, 6.16 to 80.53; P<0.001) were the only independent
      predictors of resolution. CONCLUSIONS: Oxacillin resistance and vancomycin use as
      the first treatment strongly influence the resolution rate in CNS peritonitis,
      which reinforces the validity of the International Society for Peritoneal
      Dialysis guidelines on monitoring bacterial resistance to define protocols for
      initial treatment. These results also suggest that the presence of biofilm is a
      potential cause of repeat peritonitis episodes.

PMID- 24677561
TI  - Employment pathways and work-related issues in head and neck cancer survivors.
AB  - BACKGROUND: In this exploratory study, employment and psychological factors were
      investigated in head and neck cancer survivors with survivorship of >=2 years.
      METHODS: Fifty-five head and neck cancer survivors <=60 years old completed a
      survey including subscales from the Functional Assessment of Cancer Therapy
      (FACT) instrument, the Miller Behavioral Style Scale, the General Perceived Self
      Efficacy Scale, the Patient Health Questionnaire-9 (PHQ-9), and the Hornheider
      Fragebogen short version (HFB) measuring the need for psychological
      interventions. Exploratory analyses of associations to the employment status were
      performed. RESULTS: The rate of employed patients dropped from three-fourths of
      patients before diagnosis to one-third at an average of 66.8 months after
      diagnosis. Current unemployment was associated with harder physical work before
      cancer diagnosis, surgical treatment, and current risky alcohol consumption.
      Unemployed survivors reported decreased FACT functional and social well-being and
      higher PHQ depression scores. CONCLUSION: Psychosocial variables were
      significantly related to employment. Further research is needed to examine these
      relationships.

PMID- 24677563
TI  - Treatment of singultus by sexual stimulation: Who was George T Dexter, MD (c1812
      ?)?
AB  - This short report attempts to shed light on the interesting but controversial
      personality of George T Dexter (ca1812 -?), the physician who first described
      manipulation of the female genitalia in a hysterical impressionable girl as being
      associated with the termination of singultus. Although his interaction with the
      young female patient would not meet today's ethical standards, his medical
      observation was valid and contributes to our understanding of the pathophysiology
      of singultus. He was well ahead of his colleagues who presented hiccup therapy
      case reports with similar or related pathophysiology mechanisms some 150 years
      later. 

PMID- 24677562
TI  - Reduction of motion artifacts in carotid MRI using free-induction decay
      navigators.
AB  - PURPOSE: To develop a framework for prospective free-induction decay (FID)-based
      navigator gating for suppression of motion artifacts in carotid magnetic
      resonance imaging (MRI) and to assess its capability in vivo. MATERIALS AND
      METHODS: An FID-navigator, comprising a spatially selective low flip-angle sinc
      pulse followed by an analog-to-digital converter (ADC) readout, was added to a
      conventional turbo spin-echo (TSE) sequence. Real-time navigator processing
      delivered accept/reject-and-reacquire decisions to the sequence. In this
      Institutional Review Board (IRB)-approved study, seven volunteers were scanned
      with a 2D T2-weighted TSE sequence. A reference scan with volunteers instructed
      to minimize motion as well as nongated and gated scans with volunteers instructed
      to perform different motion tasks were performed in each subject. Multiple image
      quality measures were employed to quantify the effect of gating. RESULTS: There
      was no significant difference in lumen-to-wall sharpness (2.3 +/- 0.3 vs. 2.3 +/-
      0.4), contrast-to-noise ratio (CNR) (9.0 +/- 2.0 vs. 8.5 +/- 2.0), or image
      quality score (3.1 +/- 0.9 vs. 2.6 +/- 1.2) between the reference and gated
      images. For images acquired during motion, all image quality measures were higher
      (P < 0.05) in the gated compared to nongated images (sharpness: 2.3 +/- 0.4 vs.
      1.8 +/- 0.5, CNR: 8.5 +/- 2.0 vs. 7.2 +/- 2.0, score: 2.6 +/- 1.2 vs. 1.8 +/-
      1.0). CONCLUSION: Artifacts caused by the employed motion tasks deteriorated
      image quality in the nongated scans. These artifacts were alleviated with the
      proposed FID-navigator.

PMID- 24677564
TI  - The four medical theses of Samuel Hahnemann (1755-1843).
AB  - Samuel Hahnemann, the founder of homoeopathy, over a period of 33 years wrote
      four medical theses at three different universities. The first, in 1779 at the
      University of Erlangen, Franconia, dealt with agents that allegedly induce
      spasms, granting him a MD degree. The second two theses in 1784 dealt with
      obstetrical matters and were imposed upon him by the University of Wittenberg,
      Saxony, for becoming a medical officer, a position he apparently aspired to
      mostly for financial reasons. The fourth thesis in 1812 at the University of
      Leipzig, Saxony, his most elaborate dissertation on a toxic plant, white
      hellebore, served as a habilitation, allowing him to hold university lectures in
      order to disseminate his new ideas. 

PMID- 24677565
TI  - Truncated ambition: Thomas King Chambers, MD (1817-1889).
AB  - Thomas King Chambers clearly intended to be a physician of note and at times
      indeed he was mentioned in the same breath as Sir James Paget (1814-1899), Sir
      Henry Acland (1815-1900) and Francis Anstie (1833-1874). At the time of his death
      his career was pronounced 'less than brilliant though far from inglorious'. He
      had made all the right political moves-networking through the medical societies,
      marrying well and even accompanying the Prince of Wales on his first foreign
      tour. He wanted to be more than a society doctor, however: he published his
      clinical lectures and original research, proposed a new paradigm for medicine
      that he dubbed 'the renewal of life' and found his ideas taken up
      enthusiastically in the United States. Alas, his career foundered when he
      suffered an aneurysm and underwent amputation through the thigh. Nevertheless, he
      made significant contributions to the profession through his service on the
      General Medical Council and to medical education, in particular to medical
      education for women, through his strong support of the London School of Medicine
      for Women. To examine his life is to revisit what makes a life meaningful and
      worthwhile, for Chambers' life, unlike his body, is remarkably whole. 

PMID- 24677566
TI  - Lady Brilliana Harley (1598-1643): Her medicines and her doctors.
AB  - Lady Brilliana Harley was the redoubtable chatelaine of Brampton Bryan Castle in
      Herefordshire during the mid-seventeenth century. Her many letters reveal much
      about the medications which she dispensed to her family and about the family's
      medical attendants. Whenever possible the Harleys preferred to consult university
      educated physicians rather than the local apothecary or surgeon. These physicians
      are all known from other sources but Brilliana's letters add to what is known of
      their provincial practices. In particular, they reveal their willingness to
      undertake blood-letting, often thought to be the province of the more lowly
      surgeon, and they emphasise the great distances travelled by these practitioners
      and the difficulties faced by two of them during the Civil War. 

PMID- 24677567
TI  - Catholic unionism and heterodoxy in Irish Victorian Medicine: A biography of
      Thomas More Madden (1838-1902).
AB  - It is not easy to precis the life of gynaecologist and obstetrician Thomas More
      Madden. Aside from his prolific penmanship and championing of societal issues, a
      study of his life serves to demonstrate the crossroads at which orthodox medicine
      stood during the late nineteenth century - a period of transition between
      'heroic' and modern health care. Reflecting this state of flux, Madden wrote
      several books about childbirth but he was also interested in heterodox subjects
      including heliotherapy and hydrotherapy. His political beliefs were no less
      eclectic. On one hand he was a Catholic 'Unionist', in favour of maintaining
      Ireland's place in the UK, but his writing was also imbued with the spirit of the
      Gaelic literary revival. Through his work he tried to make a case, not just for
      Ireland's place in the western health care tradition but also for its
      contribution to contemporary medicine. 

PMID- 24677568
TI  - Agop Handanian (1834-1899): Forensic medicine Professor in Imperial School of
      Medicine.

PMID- 24677569
TI  - One-pot magnetic field induced formation of Fe3O4/C composite microrods with
      enhanced lithium storage capability.
AB  - One-dimensional Fe3O4/C composite microrods are synthesized via a facile one-pot
      solvothermal reaction in the presence of an external magnetic field. When
      evaluated as an anode material for lithium ion batteries, these Fe3O4/C microrods
      manifest high specific capacity and excellent cycling performance.

PMID- 24677570
TI  - Classical endocannabinoid-like compounds and their regulation by nutrients.
AB  - Endocannabinoid-like compounds are structurally related to the true
      endocannabinoids but do not contain highly unsaturated fatty acids, and they do
      not bind the cannabinoid receptors. The classical endocannabinoid-like compounds
      include N-acylethanolamines and 2-monoacylglycerols, and their structural
      resemblance to the endocannabinoids makes them players in the endocannabinoid
      system, where they can interfere with the actions of the true endocannabinoids,
      because they in several cases engage the same synthesizing and degrading enzymes.
      In addition they have pharmacological actions of their own, which are
      particularly interesting in a nutritional and metabolic context. Exogenously
      supplied oleoylethanolamide, palmitoylethanolamide, and linoleoylethanolamide
      have anorexic effects, and the endogenous formation of these N-acylethanolamines
      in the small intestine may serve an important role in regulating food intake,
      through signaling via PPARalpha and the vagus nerve to the brain appetite center.
      A chronic high-fat diet will decrease intestinal levels of these anorectic N
      acylethanolamines and this may contribute to the hyperphagic effect of high-fat
      diet; 2-monoacylglycerols mediate endocrine responses in the small intestine;
      probably trough activation of GPR119 on enteroendocrine cells, and diet-derived 2
      monoacylglycerols, for example, 2-oleoylglycerol and 2-palmitoylglycerol might be
      important for intestinal fat sensing. Whether these 2-monoacylglycerols have
      signaling functions in other tissues is unclear at present.

PMID- 24677571
TI  - Staged pulmonary valve balloon dilatation in patients with severe pulmonary valve
      stenosis and heart failure.

PMID- 24677572
TI  - Identification and characterization of a welwitindolinone alkaloid biosynthetic
      gene cluster in the stigonematalean Cyanobacterium Hapalosiphon welwitschii.
AB  - The identification of a 36 kb welwitindolinone (wel) biosynthetic gene cluster in
      Hapalosiphon welwitschii UTEX B1830 is reported. Characterization of the enzymes
      responsible for assembling the early biosynthetic intermediates geranyl
      pyrophosphate and 3-((Z)-2'-isocyanoethenyl)indole as well as a dedicated N
      methyltransferase in the maturation of N-methylwelwitindolinone C isothiocyanate
      solidified the link between the wel pathway and welwitindolinone biosynthesis.
      Comparative analysis of the ambiguine and welwitindolinone biosynthetic pathways
      in two different organisms provided insights into the origins of diverse
      structures within hapalindole-type molecules.

PMID- 24677573
TI  - New frontiers in the evolution of fin development.
AB  - The locomotory appendages of vertebrates have undergone significant changes
      during evolution, which likely promoted a wide range of adaptive strategies.
      These appendages first evolved as unpaired finfolds in the dorsal midline of
      early chordates, more than 500 million years ago. Later on, during vertebrates'
      radiation, two sets of locomotory appendages emerged, developing from both sides
      of the latero-ventral body wall. The morphology of these paired fins in fishes at
      different phylogenetic positions suggests an evolutionary tendency for increasing
      elaboration of the endoskeleton and concomitant reduction of the distal
      dermoskeleton. This evolutionary process culminated with the origin of limbs in
      the lineages leading to tetrapods. The developmental programs responsible for the
      evolution of vertebrate appendages have been a major topic for evolutionary
      developmental biology recently. Gene expression comparisons performed in
      chordates explored how these mechanisms were transferred from a midline to latero
      ventral position. On another front, gene function assays have begun to test
      classical hypotheses concerning the transition from fish fins to tetrapod limbs.
      In this review, we highlight these recent findings on the evolution of vertebrate
      fin development. First, we discuss new perspectives on the transition from
      midline to paired appendages focus on (i) origin and molecular regionalization of
      the lateral plate mesoderm and (ii) novel ectodermic competency zones for fin
      induction. Next, we review recent work exploring how tetrapod limbs evolved from
      fish fins, considering (i) molecular and structural changes in the distal
      ectoderm of fins and (ii) modulation of 5'HoxD transcription during fin
      endoskeleton development.

PMID- 24677574
TI  - Accuracy of a computer-assisted planning and placement system for anatomical
      femoral tunnel positioning in anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Femoral tunnel positioning is a difficult, but important factor in
      successful anterior cruciate ligament (ACL) reconstruction. Computer navigation
      can improve the anatomical planning procedure besides the tunnel placement
      procedure. METHODS: The accuracy of the computer-assisted femoral tunnel
      positioning method for anatomical double bundle ACL-reconstruction with a three
      dimensional template was determined with respect to both aspects for AM and PL
      bundles in 12 cadaveric knees. RESULTS: The accuracy of the total tunnel
      positioning procedure was 2.7 mm (AM) and 3.2 mm (PL). These values consisted of
      the accuracies for planning (AM:2.9 mm; PL:3.2 mm) and for placement (about 0.4
      mm). The template showed a systematic bias for the PL-position. CONCLUSIONS: The
      computer-assisted templating method showed high accuracy for tunnel placement and
      has promising capacity for application in anatomical tunnel planning. Improvement
      of the template will result in an accurate and robust navigation system for
      femoral tunnel positioning in ACL-reconstruction.

PMID- 24677575
TI  - Biocompatibility improvement of titanium implants by coating with hybrid
      materials synthesized by sol-gel technique.
AB  - Organic-inorganic hybrid materials based on zirconia and polyethylene glycol
      (PEG) have been synthesized via sol-gel method in the present study. Those
      materials, still in the sol phase, have been used to coat a titanium grade 4 (Ti
      4) substrate to improve its biological properties. Dip-coating technique has been
      used to obtain thin films. PEG, a biocompatible polymer, used as the organic
      phase, has been incorporated with different percentages in an inorganic zirconium
      based matrix. Those hybrids have been characterized by Fourier transform infrared
      spectroscopy (FTIR) to detect interactions between the two phases. The films have
      been examined using SEM to detect morphological changes with PEG percentages. The
      potential applications of the hybrid coatings in biomedical field have been
      evaluated by bioactivity and cytotoxicity tests. The coated titanium was immersed
      in simulated body fluid (SBF) for 21 days and the hydroxyapatite deposition on
      its surface was subsequently evaluated, as that feature can be used as an index
      of bone-bonding capability. SEM equipped with energy dispersive spectrometer
      (EDS) was used to examine hydroxyapatite formation. NIH 3T3 mouse embryonic
      fibroblast cells were seeded on specimens to evaluate cells-materials
      interactions and cell vitality was inspected using WST-8 Assay.

PMID- 24677576
TI  - Spatial patterns of genome-wide expression profiles reflect anatomic and fiber
      connectivity architecture of healthy human brain.
AB  - Unraveling the relationship between molecular signatures in the brain and their
      functional, architectonic, and anatomic correlates is an important
      neuroscientific goal. It is still not well understood whether the diversity
      demonstrated by histological studies in the human brain is reflected in the
      spatial patterning of whole brain transcriptional profiles. Using genome-wide
      maps of transcriptional distribution of the human brain by the Allen Brain
      Institute, we test the hypothesis that gene expression profiles are specific to
      anatomically described brain regions. In this work, we demonstrate that this is
      indeed the case by showing that gene similarity clusters appear to respect
      conventional basal-cortical and caudal-rostral gradients. To fully investigate
      the causes of this observed spatial clustering, we test a connectionist
      hypothesis that states that the spatial patterning of gene expression in the
      brain is simply reflective of the fiber tract connectivity between brain regions.
      We find that although gene expression and structural connectivity are not
      determined by each other, they do influence each other with a high statistical
      significance. This implies that spatial diversity of gene expressions is a result
      of mainly location-specific features but is influenced by neuronal connectivity,
      such that like cellular species preferentially connects with like cells.

PMID- 24677577
TI  - Electronic clinical laboratory test results data tables: lessons from Mini
      Sentinel.
AB  - PURPOSE: Developing electronic clinical data into a common data model posed
      substantial challenges unique from those encountered with administrative data. We
      present here the design, implementation, and use of the Mini-Sentinel Distributed
      Database laboratory results table (LRT). METHODS: We developed the LRT and guided
      Mini-Sentinel data partners (DPs) in populating it from their source data. Data
      sources included electronic health records and internal and contracted clinical
      laboratory systems databases. We employed the Logical Observation Identifiers,
      Names, and Codes (LOINC(r)) results reporting standards. We evaluated transformed
      results data using data checks and an iterative, ongoing characterization and
      harmonization process. RESULTS: Key LRT variables included test name,
      subcategory, specimen source, LOINC, patient location, specimen date and time,
      result unit, and unique person identifier. Selected blood and urine chemistry,
      hematology, coagulation, and influenza tests were included. Twelve DPs with
      outpatient test results participated; four also contributed inpatient test
      results. As of September 2013, the LRT included 385,516,239 laboratory test
      results; data are refreshed at least quarterly. LOINC availability and use varied
      across DP. Multiple data quality and content issues were identified and
      addressed. CONCLUSION: Developing the LRT brought together disparate data sources
      with no common coding structure. Clinical laboratory test results obtained during
      routine healthcare delivery are neither uniformly coded nor documented in a
      standardized manner. Applying a systematic approach with data harmonization
      efforts and ongoing oversight and management is necessary for a clinical
      laboratory results data table to remain valid and useful.

PMID- 24677578
TI  - Comparing family accommodation in pediatric obsessive-compulsive disorder,
      anxiety disorders, and nonanxious children.
AB  - BACKGROUND: Family accommodation describes ways in which parents modify their
      behavior to help a child avoid or alleviate distress caused by emotional
      disorders. Accommodation is associated with increased symptom severity, lower
      functioning, and poorer treatment outcomes. Accommodation is prevalent in
      childhood obsessive-compulsive disorder (OCD) and anxiety disorders (ADs) but no
      studies have compared accommodation in these groups or compared them to healthy
      controls to ascertain if accommodation is prevalent in the general population.
      This study addresses these gaps by comparing patterns of accommodation, factors
      that maintain accommodation, and its relation to symptom severity in OCD and AD,
      relative to healthy controls. METHOD: We directly compared reports of
      accommodation to childhood OCD (N = 26) and AD (N = 31), and a comparison group
      of nonanxious (NA) children (N = 30). Mothers completed measures of accommodation
      (Family Accommodation Scale (FAS)/Family Accommodation Scale-Anxiety (FASA)),
      anxiety (Screen for Childhood Anxiety Related Emotional Disorders-Parent Report
      (SCARED-PR)), and OCD (Children's Yale-Brown Obsessive Compulsive Scale
      (CYBOCS)). RESULTS: Family accommodation is prevalent among mothers of children
      with OCD and AD. Few differences were found between the two clinical groups who
      reported more accommodation (F[2,84] = 23.411, P < .001, partial eta(2) = .358),
      greater distress (F[2,84] = 24.050, P < .001, partial eta(2) = .364), and more
      consequences of not accommodating (F[2,84] = 18.967, P < .001, partial eta(2) =
      .311), than the NA group. Accommodation was associated with severity of anxiety
      in AD (r = .426, P = .017) and OCD (r = .465, P = .017), but not in the NA group.
      CONCLUSIONS: Findings highlight family accommodation as a phenomenon that applies
      broadly and in a similar manner to children with AD and OCD. Evaluating
      accommodation provides useful information for clinical care and is an important
      part of the assessment of children with AD and OCD.

PMID- 24677579
TI  - Mutants TP53 p.R273H and p.R273C but not p.R273G enhance cancer cell malignancy.
AB  - Mutation of the tumor suppressor TP53 gene occurs in greater than half of all
      human cancers. In addition to loss of tumor suppressor function of wild-type
      TP53, gain-of-function mutations endow cancer cells with more malignant
      properties. R273 is a mutation hotspot with the p.R273H, p.R273C, and p.R273G
      variants occurring most commonly in patient samples. To better understand the
      consequences of these R273 mutations, we constructed cancer cell lines expressing
      TP53 p.R273H, p.R273C, or p.R273G and explored their characteristics. We found
      that p.R273H and p.R273C, but not p.R273G, enhanced proliferation, invasion, and
      drug resistance in vitro. Furthermore, breast cancer susceptibility protein 1 was
      upregulated by mutant TP53 p.R273H and p.R273C in response to DNA damage and
      repair. Transcriptional analysis of the TP53-R273 mutants by RNA-seq confirmed
      that the apoptosis pathway was less active in p.R273H and p.R273C, compared with
      R273G. Molecular dynamics simulation further revealed that TP53-R273G binds more
      tightly to DNA than TP53-R273H or TP53-R273C. These findings indicate that
      mutation of TP53 at a single codon has different effects, and likely clinical
      implications. p.R273H and p.R273C lead to a more aggressive phenotype than
      p.R273G. These findings may contribute to future diagnosis and therapy in TP53
      mutant cancers. 

PMID- 24677580
TI  - The effects of poly(3,4-ethylenedioxythiophene) coating on magnesium degradation
      and cytocompatibility with human embryonic stem cells for potential neural
      applications.
AB  - Magnesium (Mg) is a promising conductive metallic biomaterial due to its
      desirable mechanical properties for load bearing and biodegradability in human
      body. Controlling the rapid degradation of Mg in physiological environment
      continues to be the key challenge toward clinical translation. In this study, we
      investigated the effects of conductive poly(3,4-ethylenedioxythiophene) (PEDOT)
      coating on the degradation behavior of Mg substrates and their cytocompatibility.
      Human embryonic stem cells (hESCs) were used as the in vitro model system to
      study cellular responses to Mg degradation because they are sensitive and can
      potentially differentiate into many cell types of interest (e.g., neurons) for
      regenerative medicine. The PEDOT was deposited on Mg substrates using
      electrochemical deposition. The greater number of cyclic voltammetry (CV) cycles
      yielded thicker PEDOT coatings on Mg substrates. Specifically, the coatings
      produced by 2, 5, and 10 CV cycles (denoted as 2*-PEDOT-Mg, 5*-PEDOT-Mg, and 10*
      PEDOT-Mg) had an average thickness of 31, 63, and 78 um, respectively. Compared
      with non-coated Mg samples, all PEDOT coated Mg samples showed slower degradation
      rates, as indicated by Tafel test results and Mg ion concentrations in the post
      culture media. The 5*-PEDOT-Mg showed the best coating adhesion and slowest Mg
      degradation among the tested samples. Moreover, hESCs survived for the longest
      period when cultured with the 5*-PEDOT-Mg samples compared with the non-coated Mg
      and 2*-PEDOT-Mg. Overall, the results of this study showed promise in using PEDOT
      coating on biodegradable Mg-based implants for potential neural recording,
      stimulation and tissue engineering applications, thus encouraging further
      research.

PMID- 24677581
TI  - Huntington's Disease: Characteristics of Fallers.
AB  - INTRODUCTION: Individuals with Huntington's disease have a high prevalence of
      falls, but the specific factors that may increase the risk of falling have not
      been clearly identified in this clinical population. This study aimed to identify
      the characteristics of individuals with early to mid-stage Huntington's disease
      who had a history of falls, compared with a cohort with no history of falls.
      METHODS: Twenty-four participants (10 non-fallers and 14 recurrent fallers) with
      a diagnosis of early to mid-stage Huntington's disease were included in this
      study. Falls data were collected using retrospective survey analysis.
      Participants were assessed using measures of balance (Berg Balance Scale),
      mobility (Rivermead mobility index [RMI]), fear of falling (Activity-specific
      Balance Confidence Scale) and gait (6-min walk test; 10-m walk test self-paced
      and dual tasking). RESULTS: There was no difference in severity of disease state
      between fallers (Unified Huntington Disease Rating Scale [UHDRS] motor 25.33) and
      non-fallers (UHDRS motor 25.13) (p = 0.97). The prevalence of falls was high with
      66.7% of participants reporting at least one fall and 58.3% reporting two or more
      falls in the past 12 months. There was no difference in age or gender between
      recurrent fallers and non-fallers. Recurrent fallers had significantly lower
      scores on the Activity-specific Balance Confidence Scale (p < 0.01) and the RMI
      (p < 0.05). The probability of falling increases rapidly with a RMI score of less
      than 10. DISCUSSION: Recurrent falls are common in people with Huntington's
      disease. Individuals with a history of falls were found to have a greater fear of
      falling and lower functional mobility performance than those who did not have a
      history of falls. These measures may be useful in the identification of
      individuals with Huntington's disease who might benefit from a falls prevention
      programme. Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24677582
TI  - The first photochemical in situ production of Ti-based nanoparticles: a SH2
      strategy using bis(cyclopentadienyl)titanium dichloride (Cp2TiCl2).
AB  - Bis(cyclopentadienyl)titanium dichloride (Cp2TiCl2) is a high performance
      additive under UV light activation for both i) radical photopolymerization
      reactions (when added to a Type I photo-initiator such as 2,2-dimethoxy-2
      phenylacetophenone, the oxygen inhibition is reduced) and ii) a concomitant in
      situ photoinduced and oxygen mediated formation of Ti-based nanoparticles
      (diameters ranging from 45 to 220 nm). The photochemical properties of Cp2TiCl2
      are investigated by steady state photolysis and electron spin resonance, and its
      photoinitiation ability checked. The nanoparticles (NPs) are well characterized
      by transmission electron microscopy. The high reactivity of Cp2TiCl2 under air is
      ascribed to a bimolecular homolytic substitution (the SH2 process is clearly
      demonstrated by density functional theory calculations and ESR experiments),
      which converts the peroxyls into new efficient initiating radicals. The
      photochemical in situ incorporation of Ti NPs has never previously been reported.
      The synthesis of metal nanoparticles by a SH2 approach instead of the reduction
      of a metal salt appears to be a promising original method.

PMID- 24677583
TI  - Rare-cell enrichment by a rapid, label-free, ultrasonic isopycnic technique for
      medical diagnostics.
AB  - One significant challenge in medical diagnostics lies in the development of label
      free methods to separate different cells within complex biological samples. Here
      we demonstrate a generic, low-power ultrasonic separation technique, able to
      enrich different cell types based upon their physical properties. For malaria, we
      differentiate between infected and non-infected red blood cells in a fingerprick
      sized drop of blood. We are able to achieve an enrichment of circulating cells
      infected by the ring stage of the parasite over nonparasitized red blood cells by
      between two and three orders of magnitude in less than 3 seconds (enabling
      detection at parasitemia levels as low as 0.0005%). In a second example, we also
      show that our methods can be used to enrich different cell types, concentrating
      Trypanosoma in blood at very low levels of infection, on disposable, low-cost
      chips.

PMID- 24677584
TI  - Mixed-ligand catalysts: a powerful tool in transition-metal- catalyzed cross
      coupling reactions.
AB  - Transition-metal-catalyzed cross-coupling reactions have fundamentally
      revolutionized organic synthesis, empowering the otherwise difficult to achieve
      products with rapid and convenient accesses alongside excellent yields. Within
      these reactions, ligands often play a critical role in specifically and
      effectively advocating the corresponding catalysis. Consequently, a myriad of
      ligands have been created and applied to make a fine tuning of electronic and
      steric effect of catalysts, remarkably promoting catalytic efficiency and
      applicability. The "mixed-ligand" concept has recently emerged; by combining and
      capitalizing on the superiority of each individual ligand already available, an
      expedient way can be achieved to reach a larger extent of catalytic diversity and
      efficacy. Given the availability of a wealth of ligands, it is reasonable to have
      great expectations for the original application of mixed-ligand catalytic systems
      and their important value in organic synthesis.

PMID- 24677585
TI  - Bright white-light emission from a single organic compound in the solid state.
AB  - White-light-emitting materials and devices have attracted enormous interest
      because of their great potential for various lighting applications. We herein
      describe the light-emitting properties of a series of new difunctional organic
      molecules of remarkably simple structure consisting of two terminal 4-pyridone
      push-pull subunits separated by a polymethylene chain. They were found to emit
      almost "pure" white light as a single organic compound in the solid state, as
      well as when incorporated in a polymer film. To the best of our knowledge, they
      are the simplest white-light-emitting organic molecules reported to date. 

PMID- 24677586
TI  - High thermoelectric performance in non-toxic earth-abundant copper sulfide.

PMID- 24677587
TI  - Two series of sandwich frameworks based on two different kinds of nanosized
      lanthanide(III) and copper(I) wheel cluster units.
AB  - Two series of sandwich frameworks, [La6(MU3-OH)2(ox)3L12Cu11(MU3-X)6(MU2
      X)3].8H2O (X=Br/Cl, FJ-21 a/b; L=4-pyridin-4-yl-benzonate; ox=oxalate) and
      [Ln4(OAc)3-(H2O)4L9][Cu(MU3-I)]@[Cu10(MU3-I)(MU4-I)6(MU5-I)3].7H2O
      (Ln=Pr/Nd/Sm/Eu, FJ-22 a/b/c/d; OAc=acetate) have been hydrothermally prepared.
      These sandwich frameworks are assembled by two different kinds of nanosized
      lanthanide-(III) and copper(I) wheel cluster units, La18 and 3Cu@Cu24 in FJ-21,
      Ln24 and Cu2@Cu24 in FJ-22. The synergistic coordination between organic ligands,
      L and oxalate/acetate, leads to the formation of La18 and Ln24 wheels, while the
      synergistic coordination between organic L and inorganic Br/I ligands results in
      3Cu@Cu24 and Cu2@Cu24 wheels for FJ-21 and FJ-22, respectively. Thus, two types
      of synergistic coordination between two different organic ligands, as well as
      inorganic and organic ligands are simultaneously observed in FJ-21 and FJ-22.

PMID- 24677588
TI  - Water fluoridation almost halves hospital admissions for dental caries, report
      finds.

PMID- 24677589
TI  - Ultraflexible, freestanding nanomembranes based on poly(ethylene glycol).
AB  - Extremely elastic and highly stable nanomembranes of variable thickness (5-350
      nm) made completely of poly(ethylene glycol) are prepared by a simple procedure.
      The membranes exhibit distinct biorepulsive and hydrogel properties. They offer
      new possibilities for applications such as supports in transmission electron
      microscopy, matrices for inorganic nanoparticles, and pressure-sensitive elements
      for sensors. 

PMID- 24677590
TI  - Age-related changes in astrocytic and ependymal cells of the subventricular zone.
AB  - Neurogenesis persists in the adult subventricular zone (SVZ) of the mammalian
      brain. During aging, the SVZ neurogenic capacity undergoes a progressive decline,
      which is attributed to a decrease in the population of neural stem cells (NSCs).
      However, the behavior of the NSCs that remain in the aged brain is not fully
      understood. Here we performed a comparative ultrastructural study of the SVZ
      niche of 2-month-old and 24-month-old male C57BL/6 mice, focusing on the NSC
      population. Using thymidine-labeling, we showed that residual NSCs in the aged
      SVZ divide less frequently than those in young mice. We also provided evidence
      that ependymal cells are not newly generated during senescence, as others studies
      suggest. Remarkably, both astrocytes and ependymal cells accumulated a high
      number of intermediate filaments and dense bodies during aging, resembling
      reactive cells. A better understanding of the changes occurring in the neurogenic
      niche during aging will allow us to develop new strategies for fighting
      neurological disorders linked to senescence.

PMID- 24677591
TI  - Glycogen synthase kinase 3 beta gene structural variants as possible risk factors
      of bipolar depression.
AB  - The glycogen synthase kinase 3B (GSK3B) is an important target protein of several
      antidepressants, such as lithium, a mood stabilizer. Recent studies associated
      structural variations of the GSK3B gene to bipolar disorder (BP), although
      replications were not conclusive. Here we present data on copy number variations
      (CNVs) of the GSK3B gene probing the 9th exon region in 846 individuals (414
      controls, 172 patients with major depressive disorder (MDD) and 260 with BP). A
      significant accumulation (odds ratio: 5.5, P = 0.00051) of the amplified exon 9
      region was found in patients (22 out of 432) compared to controls (4 of 414).
      Analyzing patient subgroups, GSK3B structural variants were found to be risk
      factors of BP particularly (P = 0.00001) with an odds ratio of 8.1 while no such
      effect was shown in the MDD group. The highest odds (19.7 ratio) for bipolar
      disorder was observed in females with the amplified exon 9 region. A more
      detailed analysis of the identified GSK3B CNV by a set of probes covering the
      GSK3B gene and the adjacent NR1I2 and C3orf15 genes showed that the amplified
      sequences contained 3' (downstream) segments of the GSK3B and NR1I2 genes but
      none of them involved the C3orf15 gene. Therefore, the copy number variation of
      the GSK3B gene could be described as a complex set of structural variants
      involving partial duplications and deletions, simultaneously. In summary, here we
      confirmed significant association of the GSK3B CNV and bipolar disorder pointing
      out that the copy number and extension of the CNV varies among individuals.

PMID- 24677592
TI  - Accelerated radiotherapy for T1 to T2 glottic cancer.
AB  - BACKGROUND: Accelerated fractionation radiotherapy (RT) was administered in an
      attempt to improve the local control rates in patients with T1/T2 N0 glottic
      cancer. METHODS: Medical charts of 148 consecutive patients who had undergone RT
      using 2.4 Gray (Gy) once-daily fractionation between July 1999 and April 2007
      were reviewed. RESULTS: Of 104 patients with T1 disease treated by RT, 82
      received 60 Gy/25 fractions, and the remaining 22 with large tumor volumes and/or
      slow response to RT received 64.8 Gy/27 fractions. All 44 patients with T2
      disease received 64.8 Gy/27 fractions. The 5-year local control and overall
      survival (OS) rates were 93% and 96%, respectively, in patients with T1 disease,
      and 77% and 91%, respectively, in patients with T2 disease. No severe acute
      toxicities were observed, although 2 patients (1%) developed severe late
      toxicity. CONCLUSION: Accelerated RT for early glottic cancer is feasible, with
      encouraging local control rates.

PMID- 24677593
TI  - Preparation and in vitro cytocompatibility of chitosan-siloxane hybrid hydrogels.
AB  - Injectable systems can be used in minimally invasive surgical applications.
      Although chitosan-glycerophosphate hydrogel systems are biodegradable and
      biocompatible, the long periods of time required for their effective gelation
      have severely limited their clinical application. The challenges currently facing
      researchers in this field are therefore focused on shortening the gelation time
      and biocompatibility of these materials to develop hydrogels suitable for
      clinical application. Chitosan and gamma-glycidoxypropyltrimethoxysilane (GPTMS)
      hybrids have recently demonstrated good cytocompatibility with respect to human
      osteoblastic cells (MG63) and human bone marrow cells. Although these precursor
      sols could form gels under physiological conditions, they required neutralization
      with a sodium hydroxide solution. In this study, the chitosan-GPTMS hybrid
      systems were neutralized with glycerophosphate to prepare injectable hydrogels.
      The results revealed that the gelation time of the hydrogels could be controlled
      by the amount of GPTMS in the precursor sols. The in vitro cytocompatibility of
      the hydrogels were evaluated in terms of the proliferation of MG63 cells cultured
      either directly onto the hydrogels or indirectly onto the cell culture plate
      under a hydrogel insert. In the former case, the cells showed good attachment and
      proliferated for up to 7 days. Similar results were observed in the in direct
      culture. These results suggest that this new chitosan-GPTMS hydrogel could
      potentially be used as an injectable biomaterial in clinical applications.

PMID- 24677594
TI  - Photothermal poly(N-isopropylacrylamide)/Fe3O4 nanocomposite hydrogel as a
      movable position heating source under remote control.
AB  - Multifunctional nanocomposite hydrogel: swelling-shrink transition of the
      magnetic sensitive poly(N-isopropylacrylamide)/Fe3O4 (PNIPAM/Fe3O4) nanocomposite
      hydrogel can be controlled via near-infrared (NIR) laser exposure or non
      exposure, which shows potential as a movable position heating source manipulated
      by combination of an external magnet and near-infrared laser irradiation.

PMID- 24677595
TI  - Heterosis in age-specific selected populations of a seed beetle: sex differences
      in longevity and reproductive behavior.
AB  - We tested mutation accumulation hypothesis for the evolution of senescence using
      short-lived and long-lived populations of the seed-feeding beetle,
      Acanthoscelides obtectus (Say), obtained by selection on early- and late-life for
      many generations. The expected consequence of the mutation accumulation
      hypothesis is that in short-lived populations, where the force of natural
      selection is the strongest early in life, the late-life fitness traits should
      decline due to genetic drift which increases the frequency of mutations with
      deleterious effects in later adult stages. Since it is unlikely that identical
      deleterious mutations will increase in several independent populations, hybrid
      vigor for late-life fitness is expected in offspring obtained in crosses among
      populations selected for early-life fitness traits. We tested longevity of both
      sexes, female fecundity and male reproductive behavior for hybrid vigor by
      comparing hybrid and nonhybrid short-lived populations. Hybrid vigor was
      confirmed for male virility, mating speed and copulation duration, and longevity
      of both sexes at late ages. In contrast to males, the results on female fecundity
      in short-lived populations did not support mutation accumulation as a genetic
      mechanism for the evolution of this trait. Contrary to the prediction of this
      hypothesis, male mating ability indices and female fecundity in long-lived
      populations exhibited hybrid vigor at all assayed age classes. We demonstrate
      that nonhybrid long-lived populations diverged randomly regarding female and male
      reproductive fitness, indicating that sexually antagonistic selection, when
      accompanied with genetic drift for female fecundity and male virility, might be
      responsible for overriding natural selection in the independently evolving long
      lived populations. 

PMID- 24677596
TI  - Formation of [Bi(11)](3-) , a homoatomic, polycyclic bismuth polyanion, by
      pyridine-assisted decomposition of [GaBi(3)](2-).
AB  - Until now, polycyclic bismuth polyanions have not been known-thus discriminating
      bismuth from its lighter congeners. However, the synthesis of [K([2.2.2]crypt)]3
      (Bi11 )?2 py?tol, allows us to present the first structurally characterized
      homoatomic, polycyclic bismuth polyanion, which exhibits the [P11 ](3-) "ufosan"
      structure. It was obtained upon treatment of [K([2.2.2]crypt)]2 (GaBi3 )?en with
      the solvent pyridine. The binary Zintl anion [GaBi3 ](2-) decomposes under
      oxidative coupling of pyridine molecules and release of H2 to form the title
      compound. The unprecedented reaction, its products and by-products were
      investigated by means of spectroscopy, spectrometry, and DFT studies. All
      findings reveal the specific reaction conditions to be crucial for the formation
      of the [Bi11 ](3-) ion-and indicate the possibility of the generation and
      isolation of further, large bismuth polyanions. 

PMID- 24677597
TI  - MRI of hepatic epithelioid hemangioendothelioma (HEH).
AB  - PURPOSE: To investigate magnetic resonance imaging (MRI) characteristics of
      hepatic epithelioid hemangionendothelioma (HEH). MATERIALS AND METHODS: The study
      was exempted from formal Ethics Committee approval due to its retrospective and
      noninvasive nature. Eleven patients with histology-proven HEH were collected from
      six different institutions in a 5-year time period. In all patients a contrast
      enhanced MR study was available. Two experienced reviewers in consensus
      retrospectively noted potential MR findings of HEH. Reviewers separately analyzed
      morphological findings, tumor signal intensity, HEH contrast enhancement pattern,
      and tumor appearance on hepatobiliary phase and diffusion-weighted imaging (DWI).
      The frequency of various findings was calculated. RESULTS: The most frequent
      presentation was a peripheral distribution of the lesions (72.7%), target
      appearance on T2-weighted images (63.6%), low signal intensity on T1-weighted
      images (63.6%), ring or target-like enhancement at dynamic study (63.6%), and
      coalescence of nodules and capsular retraction (45.4%). Lack of hepatobiliary
      enhancement (5/8 patients) or "entrapment" hepatobiliary enhancement (3/8
      patients) as well as target appearance at DWI (5/6 patients) was also observed in
      our series. CONCLUSION: Although quite variable imaging appearances were seen, a
      target appearance on the T2-weighted image, ring or target enhancement at dynamic
      study, lack of enhancement or "entrapment" at hepatobiliary phase, and target
      appearance on DWI are frequent findings of HEH.

PMID- 24677600
TI  - Percutaneous antegrade scaphoid screw placement: a feasibility and accuracy
      analysis of a novel electromagnetic navigation technique versus a standard
      fluoroscopic method.
AB  - BACKGROUND: Central screw positioning in the scaphoid provides biomechanical
      advantages. METHODS: A prospective randomized study of six fluoroscopically
      guided and six electromagnetically navigated screw (ENS) placements was performed
      on human cadavers. Accuracy of screw position was determined. Intraoperative
      fluoroscopy exposure times, readjustments of drilling directions, complete
      restarts and complications were documented. RESULTS: The ENS method provided a
      mean time benefit of 7.34 min compared with the standard method and the mean
      screw length ratio (SLR coronar: ENS 0.96 +/- 0.04 mm, SFF: 0.92 +/- 0.04 mm, P =
      0.065; SLR sagittal: ENS 0.98 +/- 0.02 mm, SFF: 0.91 +/- 0.04 mm, P = 0.009) and
      the screw axis deviation angle (AD coronar: ENS 3.33 +/- 2.34 degrees , SFF:
      10.33 +/- 2.58 degrees , P = 0.002; AD sagittal: ENS 2.83 +/- 0.98 degrees , SFF:
      11.00 +/- 6.16 degrees , P = 0.002) were lower. Using the electromagnetic
      navigation procedure no drilling readjustments or restarts were required, no
      cortical breach occurred. CONCLUSIONS: Compared with the standard fluoroscopic
      technique, the ENS method used in this study showed higher accuracy, less
      complications, required less operation and radiation exposure time.

PMID- 24677601
TI  - Parent report of conversations with their adolescents with intellectual
      disability.
AB  - BACKGROUND: The purpose of this study was to examine parent report of
      conversations about difference and disability in families of adolescents with
      intellectual disability. MATERIALS AND METHODS: Participants included 50 parents
      (44 mothers, four fathers, and two other caregivers) and their adolescents with
      intellectual disability (M age = 15.9). Parents provided written responses to
      open-ended questions regarding conversations with their adolescent. Adolescents
      completed measures of self-concept and self-determination. RESULTS: The majority
      (66%) of parents reported talking to their adolescent about difference and/or
      disability. Consistent with previous research, some of these conversations were
      in response to social exclusion (e.g. child was bullied). Parents who knew the
      aetiology of their child's disability were significantly more likely to talk with
      their child about his or her disabling condition. CONCLUSIONS: Parents'
      narratives illustrate their struggle to explain disability to their adolescent.
      Professionals are challenged to consider how to promote proactive conversations
      between parents and adolescents.

PMID- 24677602
TI  - Genetic mutations in early-onset Parkinson's disease Mexican patients: molecular
      testing implications.
AB  - Mutations in PARK2, PINK1, and DJ-1 have been associated with autosomal recessive
      early-onset Parkinson's disease. Here, we report the prevalence of sequence and
      structural mutations in these three main recessive genes in Mexican Mestizo
      patients. The complete sequences of these three genes were analyzed by
      homo/heteroduplex DNA formation and direct sequencing; exon dosage was determined
      by multiplex ligation-dependent probe amplification and real-time PCR in 127
      patients belonging to 122 families and 120 healthy Mexican Mestizo controls. All
      individuals had been previously screened for the three most common LRRK2
      mutations. The presence of two mutations in compound heterozygous or homozygous
      genotypes was found in 16 unrelated patients, 10 had mutations in PARK2, six in
      PINK1, and none in DJ-1. Two PARK2-PINK1 and one PARK2-LRRK2 digenic cases were
      observed. Novel mutations were identified in PARK2 and PINK1 genes, including
      PINK1 duplication for the first time. Exon dosage deletions were the most
      frequent mutations in PARK2 (mainly in exons 9 and 12), followed by those in
      PINK1. The high prevalence of heterozygous mutations in PARK2 (12.3%) and the
      novel heterozygous and homozygous point mutations in PINK1 observed in familial
      and sporadic cases from various states of Mexico support the concept that single
      heterozygous mutations in recessive Parkinson's disease genes play a pathogenic
      role. These data have important implications for genetic counseling of Mexican
      Mestizo patients with early-onset Parkinson's disease. The presence of digenic
      inheritance underscores the importance of studying several genes in this disease.
      A step-ordered strategy for molecular diagnosis is proposed.

PMID- 24677603
TI  - Levofloxacin and proton pump inhibitor-based triple therapy versus standard
      triple first-line therapy for Helicobacter pylori eradication.
AB  - BACKGROUND: Standard triple therapy for Helicobacter pylori infection fails in up
      to one quarter of patients. Levofloxacin-based triple therapy may be more
      efficacious. OBJECTIVE: The aim of this paper was to compare levofloxacin and
      proton pump inhibitor-based triple therapy with standard triple therapy for H.
      pylori infection. METHODS: PubMed, Embase, Cochrane Central Register of
      Controlled Trials, ClinicalTrials.gov, Google Scholar, and Ovid were
      systematically searched to identify randomized controlled trials comparing
      levofloxacin and proton pump inhibitor-based therapy with standard triple therapy
      in treatment-naive patients with H. pylori infection until August 2013. RESULTS:
      Ten randomized controlled trials involving 2676 patients (1357 in the
      levofloxacin group and 1319 in the control group) met the inclusion criteria. The
      pooled odds ratio by intention-to-treat analysis and by per protocol analysis in
      the levofloxacin regimen versus standard regimen was 1.28 [95% confidence
      interval (CI): 0.88-1.85] and 1.23 (95% CI: 0.82-1.84) by the random effects
      model, respectively. There was no statistical significance of the incidence of
      total side effects between the groups, but levofloxacin-based therapy was
      associated with a significant reduction in the incidence of taste disturbance
      compared with standard third therapy. CONCLUSION: Levofloxacin-based therapy was
      as safe and effective as triple therapy for H. pylori infection and could be
      considered as an additional treatment option. However, more rigorous research is
      required to accurately assess the role of levofloxacin in eradicating H. pylori
      infection.

PMID- 24677604
TI  - D-cycloserine for treating anxiety disorders: making good exposures better and
      bad exposures worse.

PMID- 24677605
TI  - Effect of isoproterenol on myocardial perfusion, function, energy metabolism and
      nitric oxide pathway in the rat heart - a longitudinal MR study.
AB  - The chronic administration of the beta-adrenoreceptor agonist isoproterenol
      (IsoP) is used in animals to study the mechanisms of cardiac hypertrophy and
      failure associated with a sustained increase in circulating catecholamines. Time
      dependent changes in myocardial blood flow (MBF), morphological and functional
      parameters were assessed in rats in vivo using multimodal cardiac MRI. Energy
      metabolism, oxidative stress and the nitric oxide (NO) pathway were evaluated in
      isolated perfused rat hearts following 7 days of treatment. Male Wistar rats were
      infused for 7 days with IsoP or vehicle using osmotic pumps. Cine-MRI and
      arterial spin labeling were used to determine left ventricular morphology,
      function and MBF at days 1, 2 and 7 after pump implantation. Isolated hearts were
      then perfused, and high-energy phosphate compounds and intracellular pH were
      followed using 31P MRS with simultaneous measurement of contractile function.
      Total creatine and malondialdehyde (MDA) contents were measured by high
      performance liquid chromatography. The NO pathway was evaluated by NO synthase
      isoform expression and total nitrate concentration (NO(x)). In IsoP-treated rats,
      left ventricular mass was increased at day 1 and maintained. Wall thickness was
      increased with a peak at day 2 and a tendency to return to baseline values at day
      7. MBF was markedly increased at day 1 and returned to normal values between days
      1 and 2. The rate-pressure product and phosphocreatine/adenosine triphosphate
      ratio in perfused hearts were reduced. MDA, endothelial NO synthase expression
      and NO(x) were increased. Sustained high cardiac function and normal MBF after 24
      h of IsoP infusion indicate imbalance between functional demand and blood flow,
      leading to morphological changes. After 1 week, cardiac hypertrophy and decreased
      function were associated with impaired phosphocreatine, increased oxidative
      stress and up-regulation of the NO pathway. These results provide supplemental
      information on the evolution of the different contributing factors leading to
      morphological and functional changes in this model of cardiac hypertrophy and
      failure.

PMID- 24677607
TI  - Functional characterization of E. coli LptC: interaction with LPS and a synthetic
      ligand.
AB  - Lipopolysaccharide (LPS), the main cell-surface molecular constituent of Gram
      negative bacteria, is synthesized in the inner membrane (IM) and transported to
      the outer membrane (OM) by the Lpt (lipopolysaccharide transport) machinery.
      Neosynthesized LPS is first flipped by MsbA across the IM, then transported to
      the OM by seven Lpt proteins located in the IM (LptBCFG), in the periplasm
      (LptA), and in the OM (LptDE). A functional OM is essential to bacterial
      viability and requires correct placement of LPS in the outer leaflet. Therefore,
      LPS biogenesis represents an ideal target for the development of novel
      antibiotics against Gram-negative bacteria. Although the structures of Lpt
      proteins have been elucidated, little is known about the mechanism of LPS
      transport, and few data are available on Lpt-LPS binding. We report here the
      first determination of the thermodynamic and kinetic parameters of the
      interaction between LptC and a fluorescent lipo-oligosaccharide (fLOS) in vitro.
      The apparent dissociation constant (Kd) of the fLOS-LptC interaction was
      evaluated by two independent methods. The first was based on fLOS capture by
      resin-immobilized LptC; the second used quenching of LptC intrinsic fluorescence
      by fLOS in solution. The Kd values by the two methods (71.4 and 28.8 MUm,
      respectively) are very similar, and are of the same order of magnitude as that of
      the affinity of LOS for the upstream transporter, MsbA. Interestingly, both
      methods showed that fLOS binding to LptC is mostly irreversible, thus reflecting
      the fact that LPS can be released from LptC only when energy is supplied by ATP
      or in the presence of a higher-affinity LptA protein. A fluorescent glycolipid
      was synthesized: this also interacted irreversibly with LptC, but with lower
      affinity (apparent Kd=221 MUM). This compound binds LptC at the LPS binding site
      and is a prototype for the development of new antibiotics targeting LPS transport
      in Gram-negative bacteria.

PMID- 24677606
TI  - Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human
      disease.
AB  - Noncoding RNAs (ncRNAs) are classes of transcripts that are encoded by the genome
      and transcribed but never get translated into proteins. Though not translated
      into proteins, ncRNAs play pivotal roles in a variety of cellular functions.
      Here, we review the functions of long noncoding RNAs (lncRNAs) and their
      implications in various human diseases. Increasing numbers of studies demonstrate
      that lncRNAs play critical roles in regulation of protein-coding genes,
      maintenance of genomic integrity, dosage compensation, genomic imprinting, mRNA
      processing, cell differentiation, and development. Misregulation of lncRNAs is
      associated with a variety of human diseases, including cancer, immune and
      neurological disorders. Different classes of lncRNAs, their functions, mechanisms
      of action, and associations with different human diseases are summarized in
      detail, highlighting their as yet untapped potential in therapy. 

PMID- 24677608
TI  - Strategies for coordinating experimentation and modeling in integrative systems
      biology.
AB  - In this paper, we provide a novel analysis of the affordances and trade-offs of
      different strategies for integrating model-building and experimentation in
      integrative systems biology. Unimodal strategies rely on collaboration between
      experimenters and modelers in distinct laboratories. In a bimodal strategy
      modelers perform their own experiments. Each option has advantages and
      challenges. In the case of the labs we studied, the choice of strategy often
      depends on preferences held by lab directors as to the strategy that best
      achieves certain philosophical objectives concerning what they see as the aims of
      modeling in systems biology and the epistemic standards to apply to it. We
      identify an important connection between philosophical divisions in systems
      biology and the structure of research in systems biology. Better knowledge of
      these strategies and their philosophical motivations provide insight behind the
      diversifying structure of the field, and can help lab directors understand the
      challenges their researchers face, as well as the training and lab organization
      options available.

PMID- 24677609
TI  - Self-Sorting of cyclic peptide homodimers into a heterodimeric assembly featuring
      an efficient photoinduced intramolecular electron-transfer process.
AB  - We describe the thermodynamic characterisation of the self-sorting process
      experienced by two homodimers assembled by hydrogen-bonding interactions through
      their cyclopeptide scaffolds and decorated with Zn-porphyrin and fullerene units
      into a heterodimeric assembly that contains one electron-donor (Zn-porphyrin) and
      one electron-acceptor group (fullerene). The fluorescence of the Zn-porphyrin
      unit is strongly quenched upon heterodimer formation. This phenomenon is
      demonstrated to be the result of an efficient photoinduced electron-transfer
      (PET) process occurring between the Zn-porphyrin and the fullerene units of the
      heterodimeric system. The recombination lifetime of the charge-separated state of
      the heterodimer complex is in the order of 180 ns. In solution, both homo- and
      heterodimers are present as a mixture of three regioisomers: two staggered and
      one eclipsed. At the concentration used for this study, the high stability
      constant determined for the heterodimer suggests that the eclipsed conformer is
      the main component in solution. The application of the bound-state scenario
      allowed us to calculate that the heterodimer exists mainly as the eclipsed
      regioisomer (75-90 %). The attractive interaction that exists between the donor
      and acceptor chromophores in the heterodimeric assembly favours their arrangement
      in close contact. This is confirmed by the presence of charge-transfer bands
      centred at 720 nm in the absorption spectrum of the heterodimer. PET occurs in
      approximately 75% of the chromophores after excitation of both Zn-porphyrin and
      fullerene chromophores. Conversely, analogous systems, reported previously,
      decorated with extended tetrathiafulvalene and fullerene units showed a PET
      process in a significantly reduced extent (33%). We conclude that the strength
      (stability constant (K) x effective molarity (EM)) of the intramolecular
      interaction established between the two chromophores in the Zn
      porphyrin/fullerene cyclopeptide-based heterodimers controls the regioisomeric
      distribution and regulates the high extent to which the PET process takes place
      in this system.

PMID- 24677611
TI  - Carbene-9-BBN ring expansions as a route to intramolecular frustrated Lewis pairs
      for CO2 reduction.
AB  - Reactions of phosphine-derived carbenes with 9-borabicyclo[3.3.1]nonane (9-BBN)
      result in ring-expansion reactions to generate novel intramolecular frustrated
      Lewis pairs (FLPs). These FLPs effect the catalytic reduction of CO2 in the
      presence of boranes to give BOB and methoxy-borate species.

PMID- 24677610
TI  - Genome-wide DNA methylation analysis of formalin-fixed paraffin embedded
      colorectal cancer tissue.
AB  - Formalin fixation and embedding of clinical tissue samples in paraffin is a
      common method for archiving biological material. These samples are often well
      annotated and provide an invaluable resource for research. However, this process
      of fixation and storage of tissue leads to DNA damage and fragmentation. The use
      of DNA from formalin fixed, paraffin-embedded (FFPE) tissue to interrogate
      methylation levels on a genome-wide scale can pose challenges. We compared fresh
      and matched FFPE tissue DNA samples using the Illumina Infinium HD Human
      Methylation 450K BeadChip platform with a companion application for repair and
      "restoration" of DNA from FFPE tissue. Our results showed good correlation
      between fresh and FFPE sample data. FFPE DNA captured 99% of the CpG sites on the
      array on average. Significant cancer subgroups based on the CpG island methylator
      phenotype (CIMP) were clearly distinguished for both fresh and FFPE sample sets
      with cluster and scaling analysis. The DNA methylation status for the five
      standard CIMP panel genes which was evaluated for all samples by the MethyLight
      assay was correctly assigned in both fresh and FFPE samples by the array data. We
      conclude that the "restoration" method followed by assay on the Infinium HD Human
      Methylation 450K microarray can produce good quality data for DNA from FFPE
      samples.

PMID- 24677612
TI  - Effect of inhomogeneity of the electrospun fibrous scaffolds of
      gelatin/polycaprolactone hybrid on cell proliferation.
AB  - In this article, gelatin (GT) and polycaprolactone (PCL) blended with a weight
      ratio of 50:50 were dissolved in the trifluoroethanol (TFE) or the acetic acid
      doped TFE solvent system (0.2% relative to TFE) to prepare fibrous scaffolds of
      GT/PCL with different compositional and morphological homogeneities (denoted as
      the group 1 and the group 2 scaffolds) by electrospinning. The morphology and
      composition of the two groups of fibrous scaffolds were examined by scanning
      electron microscopy and Fourier transform infrared spectroscopy, respectively.
      Then, using green fluorescence protein-labeled mouse fibroblasts and HaCaT cells
      (a human keratinocyte cell line) as the model cells, cell adhesion, morphology,
      and proliferation were assessed by laser scanning confocal microscopy, scanning
      electron microscopy, and cell counting kit-8 assay, respectively. The results
      showed that the morphological and compositional inhomogeneity of the group 1
      scaffolds had a remarkable influence on cell adhesion and proliferation. In
      contrast, there was no significant difference among the group 2 scaffolds because
      of their good consistency in fiber morphology and composition. Phase separation
      resultant GT content variance in the group 1 scaffolds is suggested as one of the
      major causes. This study highlighted the importance of producing morphologically
      uniform and compositionally homogeneous composite nanofibers while
      electrospinning natural and synthetic polymer blends.

PMID- 24677613
TI  - In vivo integration of poly(epsilon-caprolactone)/gelatin nanofibrous nerve guide
      seeded with teeth derived stem cells for peripheral nerve regeneration.
AB  - Artificial nanofiber nerve guides have gained huge interest in bridging nerve
      gaps and associated peripheral nerve regeneration due to its high surface area,
      flexibility and porous structure. In this study, electrospun poly (epsilon
      caprolactone)/gelatin (PCL/Gel) nanofibrous mats were fabricated, rolled around a
      copper wire and fixed by medical grade adhesive to obtain a tubular shaped bio
      graft, to bridge 10 mm sciatic nerve gap in in vivo rat models. Stem cells from
      human exfoliated deciduous tooth (SHED) were transplanted to the site of nerve
      injury through the nanofibrous nerve guides. In vivo experiments were performed
      in animal models after creating a sciatic nerve gap, such that the nerve gap was
      grafted using (i) nanofiber nerve guide (ii) nanofiber nerve guide seeded with
      SHED (iii) suturing, while an untreated nerve gap remained as the negative
      control. In vitro cell culture study was carried out for primary investigation of
      SHED-nanofiber interaction and its viability within the nerve guides after 2 and
      16 weeks of implantation time. Walking track analysis, plantar test,
      electrophysiology and immunohistochemistry were performed to evaluate functional
      recovery during nerve regeneration. Vascularization was also investigated by
      hematoxilin/eosine (H&E) staining. Overall results showed that the SHED seeded on
      nanofibrous nerve guide could survive and promote axonal regeneration in rat
      sciatic nerves, whereby the biocompatible PCL/Gel nerve guide with cells can
      support axonal regeneration and could be a promising tissue engineered graft for
      peripheral nerve regeneration.

PMID- 24677614
TI  - Increased expression of CSP and CYP genes in adult silkworm females exposed to
      avermectins.
AB  - We analyzed 20 chemosensory protein (CSP) genes of the silkworm Bombyx mori. We
      found a high number of retrotransposons inserted in introns. We then analyzed
      expression of the 20 BmorCSP genes across tissues using quantitative real-time
      polymerase chain reaction (PCR). Relatively low expression levels of BmorCSPs
      were found in the gut and fat body tissues. We thus tested the effects of
      endectocyte insecticide abamectin (B1a and B1b avermectins) on BmorCSP gene
      expression. Quantitative real-time PCR experiments showed that a single brief
      exposure to insecticide abamectin increased dramatically CSP expression not only
      in the antennae but in most tissues, including gut and fat body. Furthermore, our
      study showed coordinate expression of CSPs and metabolic cytochrome P450 enzymes
      in a tissue-dependent manner in response to the insecticide. The function of CSPs
      remains unknown. Based on our results, we suggest a role in detecting xenobiotics
      that are then detoxified by cytochrome P450 anti-xenobiotic enzymes. 

PMID- 24677615
TI  - Pure blue-light emissive poly(oligofluorenes) with bifunctional poss in the main
      chain.
AB  - Emission of conjugated polymers is known to undergo bathochromic shift from
      solution to film formation due to pi-pi stacking in the solid state. In this
      report, a series of pearl-necklace-like hybrid polymers is designed via the
      hydrosilylation condensation between bifunctional polyhedral oligomeric
      silsesquioxanes (B-POSS) and oligofluorene segments. Optoelectronic analyses
      unequivocally show that the presence of these interconnecting B-POSS can
      effectively reduce red-shift in photoluminescence and electroluminescence during
      film formation. These hybrid poly(oligofluorenes) display stable blue emission
      with high color purity. Thermal analyses also indicate that they are vitrified
      polymers with high glass transition temperature (up to 125  degrees C). We
      believe that this strategy can be extended to other conjugated systems to control
      color purity in electroactive materials and holds promise as new emissive
      materials for various applications. 

PMID- 24677616
TI  - Equimolar carbon absorption by potassium phthalimide and in situ catalytic
      conversion under mild conditions.
AB  - Potassium phthalimide, with weak basicity, is an excellent absorbent for rapid
      carbon dioxide capture with almost equimolar absorption. This process is assumed
      to proceed through the potassium carbamate formation pathway, as supported by NMR
      spectroscopy, an in situ FTIR study, and computational calculations. Both the
      basicity and nucleophilicity of phthalimide salts have a crucial effect on the
      capture process. Furthermore, the captured carbon dioxide could more easily be
      converted in situ into value-added chemicals and fuel-related products through
      carbon capture and utilization, rather than going through a desorption process. 

PMID- 24677617
TI  - Major thrombocytopenia after balloon-expandable transcatheter aortic valve
      replacement: prognostic implications and comparison to surgical aortic valve
      replacement.
AB  - OBJECTIVES: We sought to investigate the magnitude and clinical importance of
      thrombocytopenia post transcatheter aortic valve replacement (TAVR). BACKGROUND:
      Thrombocytopenia has been observed after TAVR but has not been well studied.
      METHODS: Major thrombocytopenia (platelet count <100 * 10(9) /L) was studied
      following aortic valve interventions in a single center. Changes in platelets
      were compared in 246 patients undergoing balloon-expandable TAVR and a similar
      population of 57 cases undergoing surgical aortic valve replacement (SAVR in the
      US PARTNER IA trial). RESULTS: An early drop in platelets was seen on the day of
      intervention. The drop day 1 post procedure was similar but slightly greater with
      SAVR vs. TAVR. In both platelet counts continued to drop, reaching a nadir of
      approximately 50-60% of the baseline platelet count at day 2-3, starting to
      recover after day 5. Early major thrombocytopenia occurred post TAVR in 37% of
      patients but was not significantly related to major bleeding (OR 0.89, 95% CI
      0.51-1.60, P = 0.69) or risk of stroke (HR 0.61, 95% CI 0.16-2.20, P = 0.45);
      there was a trend to greater acute kidney injury (OR 1.76, 95% CI 0.95-3.26, P =
      0.073) and mortality (HR 1.47, 95% CI 0.98-2.22, P = 0.065). Major
      thrombocytopenia was persistent in 7.7% of patients and this was independently
      associated with mortality (HR 3.65, 95% CI 1.63-8.16, P = 0.002). CONCLUSIONS:
      Post-TAVR thrombocytopenia is a common phenomenon and its magnitude appears
      similar to that seen after SAVR. It is most often transient, not associated with
      adverse sequelae and, unless persistent, should be managed in an expectant
      fashion. (c) 2014 Wiley Periodicals, Inc.

PMID- 24677618
TI  - Jannovar: a java library for exome annotation.
AB  - Transcript-based annotation and pedigree analysis are two basic steps in the
      computational analysis of whole-exome sequencing experiments in genetic
      diagnostics and disease-gene discovery projects. Here, we present Jannovar, a
      stand-alone Java application as well as a Java library designed to be used in
      larger software frameworks for exome and genome analysis. Jannovar uses an
      interval tree to identify all transcripts affected by a given variant, and
      provides Human Genome Variation Society-compliant annotations both for variants
      affecting coding sequences and splice junctions as well as untranslated regions
      and noncoding RNA transcripts. Jannovar can also perform family-based pedigree
      analysis with Variant Call Format (VCF) files with data from members of a family
      segregating a Mendelian disorder. Using a desktop computer, Jannovar requires a
      few seconds to annotate a typical VCF file with exome data. Jannovar is freely
      available under the BSD2 license. Source code as well as the Java application and
      library file can be downloaded from http://compbio.charite.de (with tutorial) and
      https://github.com/charite/jannovar. 

PMID- 24677619
TI  - On the remarkably different role of salt in the cross-coupling of arylzincs from
      that seen with alkylzincs.
AB  - The role of halide salt additives has been investigated in the Negishi reaction
      involving aryl zinc reagents. Diarylzincs readily transmetallate to Pd in
      relatively non-polar media (e.g., THF) with zero salt present and coupling
      proceeds. Arylzinc halides (ArZnX) fail to couple in THF without salt, but do
      couple with it. However, unlike alkylzincs that form higher-order zincates in
      order to facilitate transmetallation, all that is required with arylzincs in an
      increase in solvent dielectric as even ZnX2 works as an additive, which
      completely terminates alkylzinc coupling. 

PMID- 24677620
TI  - Room-temperature amination of deactivated aniline and aryl halide partners with
      carbonate base using a Pd-PEPPSI-IPentCl-o-picoline catalyst.
AB  - Current state-of-the-art protocols for the coupling of unreactive amines (e.g.,
      electron-poor anilines) with deactivated oxidative-addition partners (e.g.,
      electron-rich and/or hindered aryl chlorides) involve strong heating (usually
      >100 degrees C) and/or tert-butoxide base, and even then not all couplings are
      successful. The aggressive base tert-butoxide reacts with and in many instances
      destroys the typical functional groups that are necessary for the function of
      most organic molecules, such as carbonyl groups, esters, nitriles, amides,
      alcohols, and amines. The new catalyst described herein, Pd-PEPPSI-IPentCl-o
      picoline, is able to aminate profoundly deactivated coupling partners when using
      only carbonate base at room temperature.

PMID- 24677621
TI  - SWIFT-scalable clustering for automated identification of rare cell populations
      in large, high-dimensional flow cytometry datasets, part 1: algorithm design.
AB  - We present a model-based clustering method, SWIFT (Scalable Weighted Iterative
      Flow-clustering Technique), for digesting high-dimensional large-sized datasets
      obtained via modern flow cytometry into more compact representations that are
      well-suited for further automated or manual analysis. Key attributes of the
      method include the following: (a) the analysis is conducted in the
      multidimensional space retaining the semantics of the data, (b) an iterative
      weighted sampling procedure is utilized to maintain modest computational
      complexity and to retain discrimination of extremely small subpopulations
      (hundreds of cells from datasets containing tens of millions), and (c) a
      splitting and merging procedure is incorporated in the algorithm to preserve
      distinguishability between biologically distinct populations, while still
      providing a significant compaction relative to the original data. This article
      presents a detailed algorithmic description of SWIFT, outlining the application
      driven motivations for the different design choices, a discussion of
      computational complexity of the different steps, and results obtained with SWIFT
      for synthetic data and relatively simple experimental data that allow validation
      of the desirable attributes. A companion paper (Part 2) highlights the use of
      SWIFT, in combination with additional computational tools, for more challenging
      biological problems.

PMID- 24677622
TI  - Assessment of the intrinsic radiosensitivity of glioma cells and monitoring of
      metabolite ratio changes after irradiation by 14.7-T high-resolution 1H MRS.
AB  - Gliomas are the most common type of primary brain tumor. Radiation therapy (RT)
      is the primary adjuvant treatment to eliminate residual tumor tissue after
      surgery. However, the current RT guided by conventional imaging is
      unsatisfactory. A fundamental question is whether it is possible to further
      enhance the effectiveness and efficiency of RT based on individual
      radiosensitivity. In this research, to probe the correlation between
      radiosensitivity and the metabolite characteristics of glioma cells in vitro, a
      perchloric acid (PCA) extracting method was used to obtain water-soluble
      metabolites [such as N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and
      succinate (Suc)]. Spectral patterns from these processed water-soluble metabolite
      samples were acquired by in vitro 14.7-T high-resolution 1H MRS. Survival
      fraction analysis was performed to test the intrinsic radiosensitivity of glioma
      cell lines. Good 1H MRS of PCA extracts from glioma cells was obtained. The
      radiosensitivity of glioma cells correlated positively with the Cho/Cr and
      Cho/NAA ratios, but negatively with the Suc/Cr ratio. Irradiation of the C6 cell
      line at different X-ray dosages led to changes in metabolite ratios and apoptotic
      rates. A plateau phase of metabolite ratio change and a decrease in apoptotic
      rate were found in the C6 cell line. We conclude that in vitro high-resolution 1H
      MRS possesses the sensitivity required to detect subtle biochemical changes at
      the cellular level. 1H MRS may aid in the assessment of the individual
      radiosensitivity of brain tumors, which is pivotal in the identification of the
      biological target volume.

PMID- 24677623
TI  - Preoperative trajectory planning for closed reduction of long-bone diaphyseal
      fracture using a computer-assisted reduction system.
AB  - BACKGROUND: Balancing reduction accuracy with soft-tissue preservation is a
      challenge in orthopaedics. Computer-assisted orthopaedic surgery (CAOS) can
      improve accuracy and reduce radiation exposure. However, previous reports have
      not summarized the fracture patterns to which CAOS has been applied. METHODS: We
      used a CAOS system and a stereolithography model to define a new fracture
      classification. Twenty reduction tests were performed to evaluate the
      effectiveness of preoperative trajectory planning. RESULTS: Twenty tests ran
      automatically and smoothly. Only three slight scratches occurred. Seventy-six
      path points represented displacement deviations of < 2 mm (average < 1 mm) and
      angulation deviation of < 1.5 degrees . DISCUSSION: Because of the strength of
      muscles, mechanical sensors are used to prevent iatrogenic soft-tissue injury.
      Secondary fractures are prevented mainly through preoperative trajectory
      planning. Based on our data, a 1 mm gap between the edges of fractures spikes is
      sufficient to avoid emergency braking from spike interference.

PMID- 24677624
TI  - Health secretary announces plan to cut NHS litigation costs.

PMID- 24677625
TI  - Near-field hyperspectral optical imaging.
AB  - This Minireview presents an overview of near-field hyperspectral imaging and
      discusses its applications. Based on a fibre-tip probe, the hyperspectral near
      field optical microscope allows the simultaneous acquisition of near-field images
      over a broad spectral range (400 to 1000 nm), enabling the recovery of local
      spectroscopic information, which is essential for understanding the resonant
      interaction of light with nanostructured objects because the far-field and near
      field spectral responses can differ significantly, as is the case for plasmonic
      nanostructures. The optical information is collected through local interactions
      with the evanescent fields at the surface of the sample; therefore, the approach
      provides spectroscopic information with nanoscale spatial resolution. Several
      applications of spectroscopic near-field microscopy are described for the
      visualisation of plasmonic modes in metallic nanostructures and near-field
      fluorescence spectroscopy.

PMID- 24677626
TI  - Abstracts of the 7th Asian Pacific Congress of Heart Failure, 17-19th April 2014,
      Bali, Indonesia.

PMID- 24677628
TI  - Observation and inpatient status: clinical impact of the 2-midnight rule.
AB  - BACKGROUND: In response to growing concern over frequency and duration of
      observation encounters, the Centers for Medicare and Medicaid Services enacted a
      rules change on October 1, 2013, classifying most hospital encounters of <2
      midnights as observation, and those >=2 midnights as inpatient. However, limited
      data exist to predict the impact of the new rule. OBJECTIVE: To answer the
      following: (1) Will the rule reduce observation encounter frequency? (2) Are
      short-stay (<2 midnights) inpatient encounters often misclassified observation
      encounters? (3) Do 2 midnights separate distinct clinical populations, making
      this rule logical? (4) Do nonclinical factors such as time of day of admission
      impact classification under the rule? DESIGN, SETTING AND PATIENTS: Retrospective
      descriptive study of all observation and inpatient encounters initiated between
      January 1, 2012 and February 28, 2013 at a Midwestern academic medical center.
      MEASUREMENTS: Demographics, insurance type, and characteristics of
      hospitalization were abstracted for each encounter. RESULTS: Of 36,193
      encounters, 4,769 (13.2%) were observation. Applying the new rules predicted a
      net loss of 14.9% inpatient stays; for Medicare only, a loss of 7.4%. Less than 2
      midnight inpatient and observation stays were different, sharing only 1 of 5 top
      International Classification of Diseases, 9th Revision (ICD-9) codes, but for
      encounters classified as observation, 4 of 5 top ICD-9 codes were the same across
      the length of stay. Observation encounters starting before 8:00 am less commonly
      spanned 2 midnights (13.6%) than later encounters (31.2%). CONCLUSIONS: The 2
      midnight rule adds new challenges to observation and inpatient policy. These
      findings suggest a need for rules modification.

PMID- 24677630
TI  - Incident severe thrombocytopenia in veterans treated with pegylated interferon
      plus ribavirin for chronic hepatitis C infection.
AB  - PURPOSE: We sought to determine the incidence and risks for severe
      thrombocytopenia (platelets < 50,000/MUL) in United States Veteran patients
      treated with pegylated interferon (PEG-IFN) plus ribavirin for hepatitis C virus
      positive (HCV) chronic liver disease (CLD). METHODS: Using a retrospective,
      observational cohort study design to analyze databases from the New England
      Veterans Healthcare System, we identified 979 patients diagnosed with HCV
      positive CLD treated solely with PEG-IFN plus ribavirin. The cohort was
      stratified by pre-treatment platelet counts of 50,000-100,000/MUL (N = 90),
      >100,000-150,000/MUL (N = 162), and >150,000MUL (N = 727). The cumulative
      incidence of severe thrombocytopenia and major bleeding events were determined
      for each baseline platelet group for 48 weeks following treatment initiation.
      Multivariable Cox regression was used to identify risk factors for incident
      severe thrombocytopenia. RESULTS: Overall, severe thrombocytopenia occurred in
      6.1% (N = 60), but in 41.1% of patients with pre-treatment platelet counts 50,
      000-100,000/MUL compared with 11.7% (p < 0.001) and 0.55% (p < 0.001) in the two
      higher pre-treatment platelet groups. Most episodes occurred within the first 12
      weeks of treatment. Median nadir count for these 60 patients was 35,000/MUL
      (inter-quartile range 28,000, 44,000). Baseline platelet counts of 50,000
      100,000/MUL [adjusted hazard ratio (HR) = 3.81; 95%CI = 2.07-7.00] and hemoglobin
      <10 g/dL (adjusted HR = 3.39; 95%CI = 1.45-7.960) associated with severe
      thrombocytopenia. Major bleeding events during the 48-week observation period
      were rare (N = 5, 0.51%). CONCLUSIONS: The incidence of severe thrombocytopenia
      in a large, observational cohort of veteran patients with HCV CLD treated with
      PEG-IFN plus ribavirin was 6.1%. Low pre-treatment platelet counts and hemoglobin
      levels associated with early, incident severe thrombocytopenia.

PMID- 24677629
TI  - A genome-wide association study of clinical symptoms of dissociation in a trauma
      exposed sample.
AB  - BACKGROUND: Recent work suggests that a subset of individuals with posttraumatic
      stress disorder (PTSD) exhibit marked dissociative symptoms, as defined by
      derealization and depersonalization. A dissociative subtype of PTSD was added to
      the diagnostic criteria listed in the Diagnostic and Statistical Manual of Mental
      Disorders, Version 5 (DSM-5) to capture this presentation of PTSD. This study
      examined genetic polymorphisms for association with the symptoms that define the
      dissociative subtype of PTSD using a genome-wide approach. METHODS: The sample
      comprised 484 White, non-Hispanic, trauma-exposed veterans and their partners who
      were assessed for lifetime PTSD and dissociation using a structured clinical
      interview. The prevalence of PTSD was 60.5%. Single-nucleotide polymorphisms
      (SNPs) from across the genome were obtained from a 2.5 million SNP array.
      RESULTS: Ten SNPs evidenced suggestive association with dissociation (P < 10(
      5)). No SNPs met genome-wide significance criteria (P < 5 * 10(-8)). The peak SNP
      was rs263232 (beta = 1.4, P = 6.12 * 10(-7)), located in the adenylyl cyclase 8
      (ADCY8) gene; a second SNP in the suggestive range was rs71534169 (beta = 1.63, P
      = 3.79 * 10(-6)), located in the dipeptidyl-peptidase 6 (DPP6) gene. CONCLUSIONS:
      ADCY8 is integral for long-term potentiation and synaptic plasticity and is
      implicated in fear-related learning and memory and long-term memory
      consolidation. DPP6 is critical for synaptic integration and excitation. These
      genes may exert effects on basic sensory integration and cognitive processes that
      underlie dissociative phenomena.

PMID- 24677632
TI  - Neural substrates of visual masking by object substitution in schizophrenia.
AB  - Despite a well-known behavioral finding of visual backward masking impairment in
      schizophrenia, its underlying neural mechanism remains obscure. This study
      examined neural correlates of a distinct type of visual backward masking, object
      substitution masking (OSM), in schizophrenia. Twenty schizophrenia patients and
      26 healthy controls completed a 4-Dot OSM task and three functional localizer
      tasks for the lateral occipital (LO), human motion-sensitive (hMT+), and
      retinotopic areas in the scanner. In 4-dot masking, subjects detected a target
      that was followed by a mask consisting of 4 dots that surrounded a target.
      Stimulus-onset asynchrony (SOA) between target and mask was varied to examine the
      modulation of masking: (1) within three visual processing areas regions of
      interest (ROI) (i.e., ROI analysis) and (2) in brain regions outside the three
      visual processing areas (i.e., whole brain analysis). In the ROI analyses, LO and
      retinotopic areas showed increased peak amplitude when SOA become longer in both
      patients and controls. There was also an effect of ROI in that both groups showed
      higher activation in LO and hMT+ compared with the retinotopic areas. The whole
      brain analyses revealed a significantly activated area for longer SOAs vs. a
      short SOA in the occipital cortex in controls only, but the group contrast was
      not significant. Overall, this study did not find strong evidence for neural
      abnormalities of OSM in schizophrenia, suggesting that neural substrates of OSM
      in schizophrenia are not as compromised as those involved in the more common
      masking methods that rely on disruption of object formation.

PMID- 24677633
TI  - Development of a growth-hormone-conjugated nanodiamond complex for cancer
      therapy.
AB  - It is highly desirable to develop a therapeutic, observable nanoparticle complex
      for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists
      have been explored as cancer cell-targeting molecules for both imaging and
      therapeutic applications. In this study, a low toxicity, biocompatible,
      therapeutic, and observable GH-nanoparticle complex for specifically targeting
      growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH
      with green fluorescence protein and carboxylated nanodiamond. Moreover, we have
      shown that this complex can be triggered by laser irradiation to create a
      "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell
      line via the apoptotic pathway. This laser-mediated, cancer-targeting platform
      can be widely used in cancer therapy. 

PMID- 24677634
TI  - Visible-light-induced C-S bond activation: facile access to 1,4-diketones from
      beta-ketosulfones.
AB  - A novel method for the synthesis of 1,4-diketones from beta-ketosulfones was
      developed by means of a visible light-induced C-S bond activation process.
      Symmetrical and unsymmetrical 1,4-diketones can be easily prepared in moderate to
      good yields.

PMID- 24677631
TI  - Expanding the palette of phenanthridinium cations.
AB  - 5,6-Disubstituted phenanthridinium cations have a range of redox, fluorescence
      and biological properties. Some properties rely on phenanthridiniums
      intercalating into DNA, but the use of these cations as exomarkers for the
      reactive oxygen species (ROS), superoxide, and as inhibitors of acetylcholine
      esterase (AChE) do not require intercalation. A versatile modular synthesis of
      5,6-disubstituted phenanthridiniums that introduces diversity by Suzuki-Miyaura
      coupling, imine formation and microwave-assisted cyclisation is presented.
      Computational modelling at the density functional theory (DFT) level reveals that
      the novel displacement of the aryl halide by an acyclic N-alkylimine proceeds by
      an S(N)Ar mechanism rather than electrocyclisation. It is found that the
      displacement of halide is concerted and there is no stable Meisenheimer
      intermediate, provided the calculations consistently use a polarisable solvent
      model and a diffuse basis set.

PMID- 24677635
TI  - Angiogenic effects of borate glass microfibers in a rodent model.
AB  - The primary objective of this research was to evaluate the use of bioactive
      borate-based glass microfibers for angiogenesis in soft tissue repair
      applications. The effect of these fibers on growth of capillaries and small blood
      vessels was compared to that of 45S5 silica glass microfibers and sham implant
      controls. Compressed mats of three types of glass microfibers were implanted
      subcutaneously in rats and tissues surrounding the implant sites histologically
      evaluated 2-4 weeks post surgery. Bioactive borate glass 13-93B3 supplemented
      with 0.4 wt % copper promoted extensive angiogenesis as compared to silica glass
      microfibers and sham control tissues. The angiogenic responses suggest the copper
      containing 13-93B3 microfibers may be effective for treating chronic soft tissue
      wounds. A second objective was to assess the possible systemic cytotoxicity of
      dissolved borate ions and other materials released from implanted borate glass
      microfibers. Cytotoxicity was assessed via histological evaluation of kidney
      tissue collected from animals 4 weeks after subcutaneously implanting high
      amounts of the borate glass microfibers. The evaluation of the kidney tissue from
      these animals showed no evidence of chronic histopathological changes in the
      kidney. The overall results indicate the borate glass microfibers are safe and
      effective for soft tissue applications.

PMID- 24677637
TI  - Supranormal differential renal function in unilateral hydronephrotic kidney:
      insights from functional MR urography.
AB  - PURPOSE: To retrospectively assess supranormal differential renal function (DRF)
      in unilateral hydronephrotic kidney by functional MR urography (fMRU). MATERIALS
      AND METHODS: The ethics committees granted exempt status for this study and also
      waived the need for informed consent. A retrospective analysis was performed of
      all patients undergoing fMRU from January 2008 to November 2011. DRF was measured
      by both the area under the curve method and Rutland-Patlak plot. Glomerular DRF
      per unit of volume and kidney volumes were analyzed. Kidney volumes were compared
      with nomograms. RESULTS: Of 170 children, 3 patients (2, 12, and 14 years) with a
      left ureteropelvic junction obstruction were included. Glomerular DRF per unit of
      volume was slightly higher on the dilated side but remained within normal range
      (<55%). Dilated kidney volumes were higher on the dilated side (>=55%). The
      volumes of nondilated kidneys were within normal range. CONCLUSION: The data
      support the fact that the dilated kidney was not hyperfunctioning and that the
      nondilated kidney was not hypofunctioning. Based on these three patients, it
      could be assumed that supranormal DRF on the dilated side might be explained by a
      slight kidney volume asymmetry, in association with higher DRF per unit of
      volume, remaining within normal physiological range. J. Magn. Reson. Imaging
      2014;40:577-582. (c) 2013 Wiley Periodicals, Inc.

PMID- 24677638
TI  - Rapid determination of globin chains in red blood cells by capillary
      electrophoresis using INSTCoated fused-silica capillary.
AB  - A laboratory-made INSTCoated fused-silica capillary has been newly used for CE
      separation of four mixtures of proteins in sodium phosphate BGEs at pH 3.0 and
      2.5, respectively. The obtained separation efficiencies range from 145,000
      theoretical plates per meter for myoglobin to 1,216,000 m(-1) for lysozyme. A
      total of 49-89% of the number of theoretical plates was obtained in a commercial
      polyvinyl alcohol coated capillary compared to the INSTCoated capillary under the
      same experimental conditions, 0-86% was obtained in a laboratory polyacrylamide
      coated capillary, and only 0-6% was obtained in an uncoated fused-silica
      capillary. The RSD values for the intraday repeatability for an INSTCoated
      capillary were 0.1-1.0% (migration time) and 0.3-2.4% (peak area); RSD values for
      the interday repeatability in the same capillary are 0.6-1.4% (migration time)
      and 2.4-5.5% (peak area); RSD values for interday repeatability between different
      capillaries equaled 1.7-2.1% (migration time) and 2.8-10.9% (peak area). The
      INSTCoated capillary has been further used for rapid determination of globin
      chains isolated from red blood cells. A separation of alpha and beta chains
      prepared from adult blood has been completed in 3 min with a peak resolution of
      1.3, and the separation of alpha and (G)gamma chains prepared from newborn blood
      took 3 min with a peak resolution of 3.6.

PMID- 24677636
TI  - Genetic variation in UGT genes modify the associations of NSAIDs with risk of
      colorectal cancer: colon cancer family registry.
AB  - The use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with
      reduced risk of colorectal neoplasia. Previous studies have reported that
      polymorphisms in NSAID-metabolizing enzymes central to NSAID metabolism including
      UDP-glucuronosyltransferases (UGT) and cytochrome P450 (CYP) 2C9 may modify this
      protective effect. We investigated whether 35 functionally relevant polymorphisms
      within CYP2C9 and UGT genes were associated with colorectal cancer risk or
      modified the protective effect of NSAIDs on colorectal cancer susceptibility,
      using 1,584 colorectal cancer cases and 2,516 unaffected sibling controls from
      the Colon Cancer Family Registry. A three-SNP genotype in UGT1A6 (G-A-A; Ala7
      Thr181-Arg184) and the Asp85 variant in UGT2B15 increased the risk of colorectal
      cancer (OR 3.87; 95% CI 1.04-14.45 and OR 1.34; 95% CI 1.10-1.63, respectively).
      We observed interactions between UGT1A3 Thr78Thr (A>G) and NSAID use (P
      interaction = 0.02), a three-SNP genotype within UGT2B4 and ibuprofen use (P
      interaction = 0.0018), as well as UGT2B15 Tyr85Asp (T>G) and aspirin use (P
      interaction = 0.01). The interaction with the UGT2B4 and the UGT2B15
      polymorphisms were noteworthy at the 25% FDR level. This study highlights the
      need for further pharmacogenetic studies to identify individuals who might
      benefit from NSAID use as part of developing effective strategies for prevention
      of colorectal neoplasia. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24677639
TI  - The effect of free health care on polypharmacy: a comparison of propensity score
      methods and multivariable regression to account for confounding.
AB  - PURPOSE: Differing healthcare access has implications for public health. In
      Ireland, eligibility for free public health care is means tested. Here, we
      examine the association between healthcare access and polypharmacy while
      accounting for underlying socio-economic and health status differences. METHODS:
      Self-reported regular medication use, history of diagnosed health conditions,
      disability, socio-demographics, and objective measures of depression and anxiety
      for adults aged 50-69 years (n = 5796) were ascertained from the population
      representative Irish Longitudinal Study on Ageing. Objective measures of frailty,
      cognition, hypertension, and body mass index were also assessed for 4241
      participants. The associations between free healthcare access and polypharmacy
      and use of 15 medication classes were estimated using multivariable modified
      Poisson regression, adjustment for the propensity score, and inverse probability
      of treatment weighting by the propensity score. RESULTS: Polypharmacy was
      reported by 22% and 7% of the 1932 and 3864 participants with and without public
      healthcare coverage. Public patients had a 21-38% greater risk of polypharmacy
      depending on the method used to account for confounding. Results were less robust
      using propensity score weighting. There was evidence that classes of
      cardiovascular drugs, drugs for acid-related disorders, and analgesics were used
      more commonly in public patients. Associations were mostly unaffected after also
      accounting for objective health measures but were significantly attenuated after
      accounting for frequency of healthcare visits. CONCLUSIONS: Publically funded
      health care in Ireland leads to greater medication use in people aged 50-69
      years. This may reflect over-prescribing to public patients or restricted use
      among those who pay out of pocket.

PMID- 24677640
TI  - Conflict between women's physically active and passive leisure pursuits: the role
      of self-determination and influences on well-being.
AB  - BACKGROUND: Evidence in support of both physically active and passive leisure as
      significant contributors to well-being has surfaced around the world. However,
      for physically active, working mothers, fitting leisure into an already busy
      schedule can be challenging. The purpose of this study was to examine the
      influence of time resources and self-determination for active and passive leisure
      on conflict between these two leisure domains and the influence of this conflict
      on well-being. METHODS: A total of 66 working mothers completed validated
      questionnaires measuring satisfaction with time and motivation at baseline
      followed by two weeks of computerized diary capture to evaluate leisure
      engagement with final measures of goal conflict and well-being at the end of the
      two weeks. RESULTS: Results indicated that dissatisfaction with time resources is
      associated with increased goal conflict as are non-self-determined motivation for
      physically active leisure and self-determined motivation for passive leisure.
      Controlling for engagement in physically active and passive leisure, well-being
      is negatively influenced by goal conflict. CONCLUSIONS: Time resources, goal
      conflict, and motivation are important factors to consider in efforts to increase
      well-being among physically active working mothers. Further research is required
      to understand the influence of opposing motivational orientations on goal
      conflict.

PMID- 24677641
TI  - Single-molecule studies on the label number distribution of fluorescent markers.
AB  - Over the past decade, a vast variety of different fluorescent labeling systems
      have emerged for use in fluorescence microscopy and fluorescence-based analytical
      techniques. A difficulty frequently arising when quantifying fluorescently
      labeled samples is that the number of labels per protein is neither well defined,
      for example, due to multiple functional groups that can undergo covalent coupling
      with activated dyes, nor well known, for example, due to limited methods mostly
      estimating ensemble averages. Herein, we use a recently established method that
      evaluates the statistics of multiple photon detection events to measure the label
      number distribution of different fluorescent marker molecules at the single
      molecule level. We tested five different far-red dyes frequently used for
      fluorescence labeling and found all of them suitable for our counting method. We
      used two dyes, ATTO647N and Alexa647, to investigate the label number
      distribution of fluorescently labeled proteins. In the experiments, we found that
      the label number distribution of antibodies and streptavidin has a significant
      fraction of molecules labeled with two, three, or more fluorophores. In contrast,
      the distribution of label numbers for nanobodies resembles the one acquired for
      SNAP-tag, which can have a maximum of one label per protein. This is also
      reflected in the ensemble degree of labeling, which is in good agreement for the
      latter samples, whereas stronger deviations were observed for antibodies and
      streptavidin. Our single-molecule studies enable full characterization of the
      label number distribution for various fluorescent markers. This work puts
      quantitative studies on the stoichiometry of fluorescently tagged oligomers and
      protein aggregates into perspective.

PMID- 24677642
TI  - Expansion of the polyQ repeats in THAP11 forms intranuclear aggregation and
      causes cell G0/G1 arrest.
AB  - Polyglutamine diseases are a group of neurodegenerative disorders caused by
      expansion of a CAG repeat that encodes polyglutamine in each respective disease
      gene. The transcription factor THAP11, a member of THAP family, is involved in
      cell growth, ES cell pluripotency and embryogenesis. Previous studies suggest
      that THAP11 protein contains a 29-residue repeat polyglutamine motif and the
      number of polyglutamine ranges from 20 to 41 in Indian population. We have
      investigated the CAG numbers at the THAP11 locus in normal individuals and
      neurodegenerative disease patients of Chinese Han population and a 38Q expansion
      (THAP11(38Q)) was found in patients. Using fluorescence confocal-based cell
      imaging, THAP11(38Q) protein formed intranuclear inclusions easier than
      THAP11(29Q) in PC12 cells. Enhanced toxicity was investigated in THAP11(38Q)
      expressing cells by growth inhibition and G0/G1 arrest. CREB-mediated
      transcription activity was inhibited by THAP11(38Q). The transcription factor,
      TBP, coactivator CBP, and chaperon protein, HSP70, could be recruited to
      THAP11(38Q). These results indicate that expansion of the polyglutamine in THAP11
      forms intracellular aggregation and is toxic in PC12 cells, suggesting a putative
      role of THAP11 in polyglutamine disease. 

PMID- 24677643
TI  - Association of ischemic stroke, hormone therapy, and right to left shunt in
      postmenopausal women.
AB  - BACKGROUND: Postmenopausal hormone therapy (HT) increases the risk of venous
      thrombosis and ischemic stroke. OBJECTIVES: We postulated that HT might increase
      the risk of ischemic stroke by promoting venous clots that travel to the brain
      through a right to left shunt (RLS). METHODS: A total of 2,389 records were
      studied. After eliminating the premenopausal patients, and those with TIAs and
      non-ischemic strokes, the medical records of 1846 postmenopausal women
      hospitalized at four institutions for ischemic stroke were reviewed to identify
      those who had undergone an adequate study to assess for RLS. The proportion of
      women with a shunt in users and non-users of HT was compared in stroke patients
      and in a reference population consisting of postmenopausal women undergoing
      elective cardiac catheterization. RESULTS: There were 363 (20%) records that had
      complete data and were included in the analysis. A shunt was more prevalent in
      patients with a cryptogenic stroke than in patients with a stroke of known cause
      (55/88 (63%) vs. 53/275 (19%), P < 0.001). In patients with a stroke of known
      cause, the frequency of a shunt was similar to that in reference women 31/136
      (23%), and the proportion of women with a shunt was similar in non-users and
      current users of HT (14% vs. 20%, P = 0.40). However, among patients with a
      cryptogenic stroke, the prevalence of a shunt was 1.5 times higher in current
      users than non-users of HT (82% vs. 56%, P = 0.04). CONCLUSIONS: Approximately
      23% of older women have a RLS. HT in these women may increase the risk of
      ischemic stroke by promoting paradoxical embolism.

PMID- 24677644
TI  - (1-Adamantyl)methyl glycidyl ether: a versatile building block for living
      polymerization.
AB  - (1-Adamantyl)methyl glycidyl ether (AdaGE) is introduced as a versatile monomer
      for oxyanionic polymerization, enabling controlled incorporation of adamantyl
      moieties in aliphatic polyethers. Via copolymerization with ethoxyethyl glycidyl
      ether (EEGE) and subsequent cleavage of the acetal protection groups of EEGE,
      hydrophilic linear polyglycerols with an adjustable amount of pendant adamantyl
      moieties are obtained. The adamantyl unit permits control over thermal properties
      and solubility profile of these polymers (LCST). Additionally, AdaGE is utilized
      as a termination agent in carbanionic polymerization, affording adamantyl
      terminated polymers. Using these structures as macroinitiators for the
      polymerization of ethylene oxide affords amphiphilic, in-chain adamantyl
      functionalized block copolymers. 

PMID- 24677645
TI  - Theorizing alternative pathways through adulthood: unequal social arrangements in
      the lives of young disadvantaged men.
AB  - This chapter introduces the innovative field-based studies on disadvantaged men
      that are featured in this volume. Together, these studies of disadvantaged men
      from diverse racial and ethnic backgrounds and both urban and nonurban settings
      complement and extend recent discussions of emerging adulthood, which typically
      conceptualizes the transition to adulthood as a normative and linear process. The
      authors offer that the research presented here provides a more accurate rendering
      of the transition to adulthood for young disadvantaged men. For disadvantaged
      young men, the transition to adulthood is often complex and nonlinear, and
      features a diversity of pathways that are often overlooked in contemporary
      research on transitions to adulthood. The chapter ends with a call for research
      and theory that better reflects the precarious nature of pathways to adulthood
      for disadvantaged men in urban and nonurban settings. Researchers are encouraged
      to draw on findings from field-based studies to inform policies and practices
      directed at minimizing the marginalization of disadvantaged men from mainstream
      society.

PMID- 24677646
TI  - Taking boys out of the hood: exile as a parenting strategy for African American
      male youth.
AB  - Research indicates that inner-city neighborhood effects are correlated with
      school dropout, substance abuse, crime, violence, homicide, HIV risk related
      behaviors, and incarceration for adolescent African American males. Parents of
      adolescent African American males face many challenges as they try to keep their
      children safe in high-risk neighborhoods. Parents often use multiple parenting
      approaches to improve the life chances and opportunities for this vulnerable
      population of youth. This chapter elaborates on the concept of exile. Exile is a
      parenting strategy used by parents to relocate young African American males
      living in high-risk communities to safer spaces. Drawing on qualitative data
      collected from a longitudinal ethnographic research study on the social context
      of adolescent violence among African American males, this chapter examines exile
      as a parenting approach used to keep children safe.

PMID- 24677647
TI  - "The regular routine": proactive policing and adolescent development among young,
      poor black men.
AB  - Over the last several decades, proactive policing, in which departments use data
      on reported crimes to determine where local police officers will target their
      surveillance, has increased police contact with residents in certain
      neighborhoods. Drawing on field research conducted over a three-year period (2007
      2010) among adult and adolescent African American men in a San Francisco
      neighborhood with a concentrated poor, Black population, I provide an
      ethnographic account of routine encounters with the police that structure
      adolescent boys' daily lives in potentially significant ways. I build on Erving
      Goffman's discussion of "patterns of mortification" to describe how typical
      encounters unfold in the day-to-day lives of young men and consider the
      implications of such encounters for healthy adolescent development.

PMID- 24677648
TI  - Growing up as "man of the house": adultification and transition into adulthood
      for young men in economically disadvantaged families.
AB  - Many children in economically disadvantaged communities assume adult roles in
      their families. Negotiating the responsibilities and expectations associated with
      becoming what some young men describe as "man of the house" has important
      implications for how adolescent boys move into adulthood. In this study, we share
      insights from field work and life-history interviews with low-income, young
      African American men and Salvadoran men in the Washington, DC/Baltimore region to
      illustrate how adultification may deliver contradictory expectations for
      adolescents. The findings also show how the accelerated responsibilities that
      accompany the experience of adultification create difficulties in the young men's
      transition into adulthood. These findings indicate that the age period of
      emerging adulthood may begin earlier for economically disadvantaged young men.

PMID- 24677649
TI  - Fathers' accounts of struggle and growth in early adulthood: an exploratory study
      of disadvantaged men.
AB  - This chapter explores how fatherhood prompts struggle and growth in the
      psychological, social, and economic changes associated with the transition to
      adulthood. Little is known about these connections, especially for disadvantaged
      Latino and White fathers who live in small and mid-sized American communities. We
      draw on eight in-depth focus groups with 48 fathers (27 Latino and 21 White) who
      have children in low-income schools in a small and mid-sized American community.
      These men face significant challenges in establishing themselves at work-a
      central task of both adulthood and fatherhood-and in balancing these demands
      alongside the strong expectation that they also be involved fathers. Involved
      fathering is key to understanding dynamics related to identity and meaning and to
      relationships with spouses and friends, which are also intertwined with the
      process of becoming adult. The discussion considers how fatherhood can promote
      and constrain adult development for disadvantaged men.

PMID- 24677650
TI  - Mortality in babies with achondroplasia: revisited.
AB  - BACKGROUND: Natural history studies performed 30 years ago identifying higher
      mortality among children born with achondroplasia, a genetic dwarfing condition,
      resulted in clinical recommendations aimed at improving mortality in childhood.
      The objective of this study was to determine if mortality rates have changed over
      the past few decades. METHODS: Children born with achondroplasia during 1996 to
      2003 were ascertained from the Texas Birth Defects Registry and matched with
      death certificate data from the Bureau of Vital Statistics through 2007. Infant
      and overall mortality rates, both crude and standardized to the 2005 (SMR2005 )
      and 1975 (SMR1975 ) U.S. populations, were calculated. RESULTS: 106 children born
      with achondroplasia were identified. Four deaths were reported, with all
      occurring in the first year of life (mortality rate: 41.4 /1000 live-births).
      Infant mortality was higher when standardized to the 2005 U.S. population
      (SMR2005 :6.02, 95% CI:1.64-15.42) than the 1975 population (SMR1975 :2.58, 95%
      CI:0.70-6.61). CONCLUSION: The higher SMR2005 compared with SMR1975 , along with
      the fact that SMR1975 was nearly half that of a previous cohort reported 25 years
      ago (rate ratio: 0.53, 95% CI: 0.11-2.25), reflect a discrepancy in the changes
      in mortality in the overall population and in our cohort. Although an overall
      improvement in mortality, especially after the first year of life, is observed in
      our cohort, children with achondroplasia are still at a much higher risk of death
      compared with the general population. A longer follow-up is needed to elucidate
      whether evaluation/intervention changes have resulted in significant improvement
      in long-term survival among these patients.

PMID- 24677651
TI  - Epidemiology and course of unipolar mania: results from the national
      epidemiologic survey on alcohol and related conditions (NESARC).
AB  - BACKGROUND: Unipolar mania (UM), in which only manic episodes occur during the
      course of illness, may be an important clinical manifestation of bipolar disorder
      that is under-recognized and understudied. The aim of this study is, for the
      first time, to examine the prevalence of UM and its clinical characteristics in
      the community. METHODS: Among a total of 1,411 subjects with bipolar I disorder,
      we evaluated the prevalence of UM using three different criteria proposed in
      previous studies. We compared the clinical characteristics of subjects with UM to
      those with a more classic bipolar presentation with mania and lifetime major
      depressive episode (MDE). We additionally explored the proportion of subjects
      with UM who later experience at least one MDE during a 3-year follow-up period
      and determined risk factors for converting from UM to classic bipolar disorder.
      RESULTS: The prevalence rate of UM among those with bipolar disorder ranged from
      5.0 to 7.2% depending on the criteria. UM was more common in male and nonwhite
      subjects. About half of individuals with UM experienced subthreshold depression.
      Individuals with UM had lower rates of comorbid anxiety disorders or attention
      deficit hyperactivity disorder (ADHD). During the follow-up, about 18% of
      subjects with UM experienced MDEs. Male, nonwhite, comorbid generalized anxiety
      disorder and ADHD predicted an increased transition from UM to classic bipolar
      disorder. Subthreshold depression was not associated with the risk of the
      transition. CONCLUSIONS: UM is an infrequent but clinically distinct subtype of
      bipolar I disorder. Further research delineating the characteristics of UM is
      warranted.

PMID- 24677656
TI  - Reliability and validity of the Daily Cognitive-Communication and Sleep Profile:
      a new instrument for monitoring sleep, wakefulness and daytime function.
AB  - The Daily Cognitive Communicative and Sleep Profile (DCCASP) is a seven-item
      instrument that captures daily subjective sleep quality, perceived mood,
      cognitive, and communication functions. The objective of this study was to
      evaluate the reliability and validity of the DCCASP. The DCCASP was self
      administered daily to a convenience sample of young adults (n = 54) for two two
      week blocks, interspersed with a two-week rest period. Afterwards, participants
      completed the Pittsburgh Sleep Quality Index (PSQI). Internal consistency and
      criterion validity were calculated by Cronbach's alpha coefficient, Concordance
      Correlation Coefficient (CCC), and Spearman rank (rs) correlation coefficient,
      respectively. Results indicated high internal consistency (Cronbach-s alpha =
      0.864-0.938) among mean ratings of sleep quality on the DCCASP. There were
      significant correlations between mean ratings of sleep quality and all domains
      (rs=0.38-0.55, p<0.0001). Criterion validity was established between mean sleep
      quality ratings on the DCCASP and PSQI (rs=0.40, p<0.001). The DCCASP is a
      reliable and valid self-report instrument to monitor daily sleep quality and
      perceived mood, cognitive, and communication functions over time, amongst a
      normative sample of young adults. Further studies on its psychometric properties
      are necessary to clarify its utility in a clinical population.

PMID- 24677652
TI  - Erythropoiesis from human embryonic stem cells through erythropoietin-independent
      AKT signaling.
AB  - Unlimited self renewal capacity and differentiation potential make human
      pluripotent stem cells (PSC) a promising source for the ex vivo manufacture of
      red blood cells (RBCs) for safe transfusion. Current methods to induce
      erythropoiesis from PSC suffer from low yields of RBCs, most of which are
      immature and contain embryonic and fetal rather than adult hemoglobins. We have
      previously shown that homodimerization of the intracellular component of MPL (ic
      MPL) induces erythropoiesis from human cord blood progenitors. The goal of this
      study was to investigate the potential of ic-MPL dimerization to induce
      erythropoiesis from human embryonic stem cells (hESCs) and to identify the
      signaling pathways activated by this strategy. We present here the evidence that
      ic-MPL dimerization induces erythropoietin (EPO)-independent erythroid
      differentiation from hESC by inducing the generation of erythroid progenitors and
      by promoting more efficient erythroid maturation with increased RBC enucleation
      as well as increased gamma:epsilon globin ratio and production of beta-globin
      protein. ic-MPL dimerization is significantly more potent than EPO in inducing
      erythropoiesis, and its effect is additive to EPO. Signaling studies show that
      dimerization of ic-MPL, unlike stimulation of the wild type MPL receptor,
      activates AKT in the absence of JAK2/STAT5 signaling. AKT activation upregulates
      GATA-1 and FOXO3 transcriptional pathways with resulting inhibition of apoptosis,
      modulation of cell cycle, and enhanced maturation of erythroid cells. These
      findings open up potential new targets for the generation of therapeutically
      relevant RBC products from hPSC.

PMID- 24677657
TI  - Chief medical officer urges action to tackle overweight and obesity.

PMID- 24677658
TI  - Multidentate europium chelates as luminoionophores for anion recognition: impact
      of ligand design on sensitivity and selectivity, and applicability to enzymatic
      assays.
AB  - The design of photoluminescent molecular probes for the selective recognition of
      anions is a major challenge for the development of optical chemical sensors. The
      reversible binding of anions to lanthanide centers is one promising option for
      the realization of anion sensors, because it leads in some cases to a strong
      luminescence increase by the replacement of quenching water molecules. Yet, it is
      an open problem to gain control of the sensitivity and selectivity of the
      luminescence response. Primarily, the selective detection of (poly)phosphate
      species such as nucleotides has emerged as a demanding task, because they are
      involved in many biological processes and enzymatic reactions. We designed a
      series of pyridyl-based multidentate europium complexes (seven-, six-, and five
      dentate) including sensitizing chromophores and studied their luminescence
      intensity and lifetime responses to different (poly)phosphates (adenosine
      triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP),
      cyclic adenosine monophosphate (cAMP), pyrophosphate, and phosphate anions), and
      carboxyanions (citrate, malate, oxalacetate, succinate, alpha-ketoglutarate,
      pyruvate, oxalate, carbonate). The results reveal that the number of free
      coordination sites has a significant impact on the sensitivity and selectivity of
      the response. Because of its reversibility, the lanthanide probes can be applied
      to monitor the activity of ATP-consuming enzymes such ATPases and apyrases, which
      is demonstrated by means of the five-dentate complex. 

PMID- 24677659
TI  - Quantitative evaluation of liver function with T1 relaxation time index on Gd-EOB
      DTPA-enhanced MRI: comparison with signal intensity-based indices.
AB  - PURPOSE: To evaluate whether the reduction rate of T1 relaxation time of the
      liver (T1 relaxation time index) before and 20 minutes after gadolinium
      ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) injection has the
      potential to serve as an magnetic resonance imaging (MRI)-based liver function
      test in comparison with signal intensity-based indices. MATERIALS AND METHODS:
      Ninety-nine patients with suspected liver lesions underwent Gd-EOB-DTPA-enhanced
      MRI. T1 maps using 3D T1-weighted gradient-echo volumetric interpolated
      examination with two different flip angles were also performed before and 20
      minutes after Gd-EOB-DTPA administration. T1 relaxation time index was compared
      with four signal intensity-based indices in terms of the ability to discriminate
      Child-Pugh A (CPA) and Child-Pugh B (CPB) from normal liver function (NLF), and
      in terms of its correlation with indocyanine green (ICG) clearance. RESULTS:
      Twenty-four patients were classified as NLF, 64 patients were classified as CPA,
      and 11 were classified as CPB group. The T1 relaxation time index was
      significantly lower for CPA (0.62 +/- 0.08 vs. 0.68 +/- 0.07, P = 0.021) and CPB
      (0.55 +/- 0.15 vs. 0.68 +/- 0.07, P < 0.001) than for NLF. All signal intensity
      based indices showed significant differences only when comparing NLF and CPB. The
      correlation coefficient with ICG clearance was the highest for T1 relaxation time
      index (r = -0.605, P < 0.001). CONCLUSION: The T1 relaxation time index has the
      potential to serve as an MRI-based liver function test, and is most strongly
      correlated with ICG clearance among the Gd-EOB-DTPA MRI-based indices
      investigated.

PMID- 24677660
TI  - An integrated photoelectrochemical-chemical loop for solar-driven overall
      splitting of hydrogen sulfide.
AB  - Abundant and toxic hydrogen sulfide (H2 S) from industry and nature has been
      traditionally considered a liability. However, it represents a potential resource
      if valuable H2 and elemental sulfur can be simultaneously extracted through a H2
      S splitting reaction. Herein a photochemical-chemical loop linked by redox
      couples such as Fe(2+) /Fe(3+) and I(-) /I3 (-) for photoelectrochemical H2
      production and H2 S chemical absorption redox reactions are reported. Using
      functionalized Si as photoelectrodes, H2 S was successfully split into elemental
      sulfur and H2 with high stability and selectivity under simulated solar light.
      This new conceptual design will not only provide a possible route for using solar
      energy to convert H2 S into valuable resources, but also sheds light on some
      challenging photochemical reactions such as CH4 activation and CO2 reduction. 

PMID- 24677661
TI  - Double-pulsed diffusional kurtosis imaging.
AB  - Diffusional kurtosis imaging (DKI) is extended to double-pulsed-field-gradient (d
      PFG) diffusion MRI sequences. This gives a practical approach for acquiring and
      analyzing d-PFG data. In particular, the leading d-PFG effects, beyond what
      conventional single-pulsed field gradient (s-PFG) provides, are interpreted in
      terms of the kurtosis for a diffusion displacement probability density function
      (dPDF) in a six-dimensional (6D) space. The 6D diffusional kurtosis encodes the
      unique information provided by d-PFG sequences up to second order in the b-value.
      This observation leads to a compact expression for the signal magnitude, and it
      suggests novel data acquisition and analysis methods. Double-pulsed DKI (DP-DKI)
      is demonstrated for in vivo mouse brain with d-PFG data obtained at 7 T.
      Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24677662
TI  - Efficient plasmonic dye-sensitized solar cells with fluorescent Au-encapsulated C
      dots.
AB  - A simple strategy to improve the efficiency of a ZnO-nanorod-based dye-sensitized
      solar cell (DSSC) by use of Au-encapsulated carbon dots (Au@C-dots) in the
      photoanode is presented. The localized surface plasmonic resonance of Au in the
      500-550 nm range coupled with the ability of C-dots to undergo charge separation
      increase the energy-harvesting efficiency of the DSSC with ZnO/N719/Au@C-dots
      photoanodes. Charge transfer from N719 dye to Au@C-dots is confirmed by
      fluorescence and lifetime enhancements of Au@C-dots. Forster resonance energy
      transfer (FRET) from the gap states of ZnO nanorods to N719 dye is also ratified
      and the energy transfer rate is 4.4*10(8) s(-1) and the Forster radius is 1.89
      nm. The overall power conversion efficiency of the plasmonic and FRET-enabled
      DSSC with ZnO/N719/Au@C-dots as the photoanode, I2/I(-) as the electrolyte and
      multiwalled carbon nanotubes as the counter electrode is 4.1%, greater by 29%
      compared to a traditional ZnO/N719 cell.

PMID- 24677663
TI  - GluN2B-selective N-methyl-D-aspartate (NMDA) receptor antagonists derived from 3
      benzazepines: synthesis and pharmacological evaluation of benzo[7]annulen-7
      amines.
AB  - Given their high neuroprotective potential, ligands that block GluN2B-containing
      N-methyl-D-aspartate (NMDA) receptors by interacting with the ifenprodil binding
      site located on the GluN2B subunit are of great interest for the treatment of
      various neuronal disorders. In this study, a novel class of GluN2B-selective NMDA
      receptor antagonists with the benzo[7]annulene scaffold was prepared and
      pharmacologically evaluated. The key intermediate, N-(2-methoxy-5-oxo-6,7,8,9
      tetrahydro-5H-benzo[7]annulen-7-yl)acetamide (11), was obtained by cyclization of
      3-acetamido-5-(3-methoxyphenyl)pentanoic acid (10 b). The final reaction steps
      comprise hydrolysis of the amide, reduction of the ketone, and reductive
      alkylation, leading to cis- and trans-configured 7-(omega
      phenylalkylamino)benzo[7]annulen-5-ols. High GluN2B affinity was observed with
      cis-configured gamma-amino alcohols substituted with a 3-phenylpropyl moiety at
      the amino group. Removal of the benzylic hydroxy moiety led to the most potent
      GluN2B antagonists of this series: 2-methoxy-N-(3-phenylpropyl)-6,7,8,9
      tetrahydro-5H-benzo[7]annulen-7-amine (20 a, Ki =10 nM) and 2-methoxy-N-methyl-N
      (3-phenylpropyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine (23 a, Ki =7.9
      nM). The selectivity over related receptors (phencyclidine binding site of the
      NMDA receptor, sigma1 and sigma2 receptors) was recorded. In a functional assay
      measuring the cytoprotective activity of the benzo[7]annulenamines, all tested
      compounds showed potent NMDA receptor antagonistic activity. Cytotoxicity induced
      via GluN2A subunit-containing NMDA receptors was not inhibited by the new
      ligands.

PMID- 24677664
TI  - Differences among admitting departments in alerts and alert overrides for drug
      drug interaction.
AB  - OBJECTIVE: To determine differences in the incidence and risk factors of alerts
      for drug-drug interaction (DDI) and the rate of alert overrides by an admitting
      department. METHODS: A retrospective cohort study was performed using electronic
      health records of a Korean tertiary teaching hospital including all hospitalized
      adult patients for 18 months. The main outcome measures included incidence rates
      of alerts for DDI and their override, hazard ratios (HRs) for DDI alerts, and
      odds ratios (ORs) for alert overrides by admitting department (emergency
      department [ED], general ward [GW], and intensive care unit [ICU]) after
      adjusting for other known risk factors. RESULTS: Among 102 379 incident
      admissions, 6060 had alerts for DDI (5.4/person-year). After adjusting for
      covariates, patients admitted to the ED (HR, 4.02; confidence interval [CI], 3.69
      4.38) or ICU (HR, 1.62; CI, 1.29-2.04) showed higher risks for DDI compared with
      those admitted to the GW. The alert-override rate was significantly higher in the
      ED (OR 1.68) than in the GW; however, there was no significant difference between
      GW and ICU. The prevalence of DDI alerts and their override rate were also
      demonstrated. DISCUSSION: The incidence of DDI and the alert-override rate
      differed by admitting department. The ED and ICU were associated with higher
      risks for alerts on DDI than did the GW after adjusting for other known risk
      factors. CONCLUSIONS: Admitting department was an independent risk factor for
      alerts and alert overrides. Strategies to reduce alerts and alert overrides
      should consider the admitting department.

PMID- 24677665
TI  - Evaluation of rhBMP-2 and bone marrow derived stromal cell mediated bone
      regeneration using transgenic fluorescent protein reporter mice.
AB  - The aim of the study is use of transgenic fluorescent protein reporter mouse
      models to understand the cellular processes in recombinant human bone
      morphogenetic protein-2 (rhBMP-2) mediated bone formation. Bilateral parietal
      calvarial bone defects in Col3.6Topaz transgenic fluorescent osteoblast reporter
      mouse were used to understand the bone formation in the presence and absence of
      rhBMP2 and/or Col3.6Cyan bone marrow derived stromal cells (BMSCs), using
      collagen-hydroxyapatite matrix (Healos) as a biomaterial. The bone regeneration
      was not confined to the site of BMP-2 implantation and significant bone formation
      was observed in the neighboring defect site. Osteogenic cellular activity with
      overlying alizarin complexone staining was observed in both the defects
      indicating host cell induced mineralization. However, implantation of BMSCs along
      with rhBMP-2 demonstrated a donor cell derived bone formation. The presence of
      rhBMP-2 did not support host cell recruitment in the presence of donor cells.
      This study demonstrates the potential of multiple fluorescent reporters to
      understand the cellular processes involved in the bone regeneration process using
      biomaterials, growth factors, and/or stem cells.

PMID- 24677667
TI  - The NICS-XY-scan: identification of local and global ring currents in multi-ring
      systems.
AB  - Nucleus-independent chemical shift (NICS)-based methods are very popular for the
      determination of the induced magnetic field under an external magnetic field.
      These methods are used mostly (but not only) for the determination of the
      aromaticity and antiaromaticity of molecules and ions, both qualitatively and
      quantitatively. The ghost atom that serves as the NICS probe senses the induced
      magnetic field and reports it in the form of an NMR chemical shift. However, the
      source of the field cannot be determined by NICS. Thus, in a multi-ring system
      that may contain more than one induced current circuit (and therefore more than
      one source of the induced magnetic field) the NICS value may represent the sum of
      many induced magnetic fields. This may lead to wrong assignments of the
      aromaticity (and antiaromaticity) of the systems under study. In this paper, we
      present a NICS-based method for the determination of local and global ring
      currents in conjugated multi-ring systems. The method involves placing the NICS
      probes along the X axis, and if needed, along the Y axis, at a constant height
      above the system under study. Following the change in the induced field along
      these axes allows the identification of global and local induced currents. The
      best NICS type to use for these scans is NICSpiZZ , but it is shown that at a
      height of 1.7 A above the molecular plane, NICSZZ provides the same qualitative
      picture. This method, namely the NICS-XY-scan, gives information equivalent to
      that obtained through current density analysis methods, and in some cases,
      provides even more details. 

PMID- 24677668
TI  - Increased prosthetic valve gradients: abnormal prosthetic function or pressure
      recovery?
AB  - The non-invasive evaluation of prosthetic valve function is challenging. The
      effects of flow rate, valvular geometry, leaflet motion, and pressure recovery
      all impact the Doppler assessment of prosthetic performance. Differentiating
      prosthesis obstruction from pressure recovery in patients who are found to have
      high Doppler velocities across an aortic valve prosthesis is critical in order to
      direct appropriate management. In this manuscript, we present two cases of
      patients with aortic valve prosthesis with high Doppler velocities and review the
      pathophysiology and evaluation of prosthesis function.

PMID- 24677666
TI  - Ductuli efferentes of the male Golden Syrian hamster reproductive tract.
AB  - Efferent ductules are responsible for the transportation of spermatozoa from the
      testis to the epididymis and their epithelium is responsible for the reabsorption
      of over 90% of the luminal fluid. The purpose of this research was to
      characterize the gross morphology and histology of efferent ductules in the male
      Golden Syrian hamster. The efferent ductules emerge from rete testis with a
      unique polarity at the apex or cephalic pole of the testis. The number of
      efferent ductules varied from 3 to 10 with an average of 6.0 and blind ending
      ducts were observed in approximately 56% of the males. The ductules merged into a
      single common duct prior to entering the caput epididymidis. The proximal
      efferent ductule lumen was wider than the distal (conus and common ducts),
      consistent with reabsorption of most of the luminal fluid, as was morphology of
      the ductal epithelium. Non-ciliated cells in the proximal region had prominent
      endocytic apparatuses, showing both coated pits and apical tubules in the apical
      cytoplasm. Large basolateral, intercellular spaces were also present in the
      epithelium of the proximal region. Distal non-ciliated cells had an abundance of
      large endosomes and lysosomal granules. Localisation of sodium/hydrogen exchanger
      3 (NHE3; SLC9A3) and aquaporins 1 and 9 (AQP1, AQP9) along the microvillus border
      was also consistent with ion transport and fluid reabsorption by this epithelium.
      In comparison, the caput epididymidis epithelium expressed only AQP9
      immunostaining. Another unusual feature of the hamster efferent ductules was the
      presence of glycogen aggregates in the basal cytoplasm of small groups of
      epithelial cells, but only in the proximal ducts near the rete testis. Androgen
      (AR), estrogen (ESR1 and ESR2) and vitamin D receptors (VDR) were also abundant
      in epithelial nuclei of proximal and distal efferent ductules. In comparison,
      caput epididymidis showed very little immunostaining for ESR1. 

PMID- 24677669
TI  - Quantitative absorption cytometry for measuring red blood cell hemoglobin mass
      and volume.
AB  - We present an optical system, called the quantitative absorption cytometer (QAC),
      to measure the volume and hemoglobin mass of red blood cells flowing through a
      microfluidic channel. In contrast to clinical hematology analyzers, where cells
      are sphered in order for both volume and hemoglobin to be measured accurately,
      the QAC measures cells in their normal physiological shape. Human red blood cells
      are suspended in a refractive index-matching absorbing buffer, driven through a
      microfluidic channel, and imaged using a transmission light microscope onto a
      color camera. A red and a blue LED illuminate cells and images at each color are
      used to independently retrieve cell volume and hemoglobin mass. This system shows
      good agreement with red blood cell indices retrieved by a clinical hematology
      analyzer and in fact measures a smaller coefficient of variation of hemoglobin
      concentration. In addition to cell indices, the QAC returns height and mass maps
      of each measured cell. These quantitative images are valuable for analyzing the
      detailed morphology of individual cells as well as statistical outliers found in
      the data. We also measured red blood cells in hypertonic and hypotonic buffers to
      quantify the correlation between volume and hemoglobin mass under osmotic stress.
      Because this method is invariant to cell shape, even extremely nonspherical cells
      in hypertonic buffers can be measured accurately.

PMID- 24677671
TI  - Surprisingly complex life: Sue Leung's story.
AB  - INTRODUCTION: While numerous studies relating to the lives of intellectually
      challenged people have been published previously, most have been from the
      caregiver's perspective and lack an insider's view. In addition, none of them
      were conducted in a Chinese context. Our purpose is to fill this gap by studying
      the life of Sue Leung, an intellectually disabled Chinese woman in Hong Kong.
      METHODS: Using a narrative approach that combined interviews and observational
      data collected over an extended time period, the research sought a holistic
      understanding of her life, how she interacts with others and the challenges and
      difficulties she faces. RESULTS: Sue Leung's life proved to be complex with
      social, spiritual, psychological, sexual and financial dimensions. Her story, in
      which she herself and other mentally impaired people are the actors, reflects to
      some degree the world of mentally impaired people, at least in Hong Kong. Their
      world is just as complex as that of anyone else. Violence, dangers, romances,
      friendships and goodwill also exist in that world. DISCUSSION: Sue Leung's story
      has helped to unravel the various dimensions of her life and enabled a deeper
      understanding of the challenges and difficulties a mildly intellectually disabled
      woman has to face in her life in Hong Kong. Social implications are discussed,
      and recommendations are made for future research.

PMID- 24677672
TI  - Mesoporous Prussian blue analogues: template-free synthesis and sodium-ion
      battery applications.
AB  - The synthesis of mesoporous Prussian blue analogues through a template-free
      methodology and the application of these mesoporous materials as high-performance
      cathode materials in sodium-ion batteries is presented. Crystalline
      mesostructures were produced through a synergistically coupled nanocrystal
      formation and aggregation mechanism. As cathodes for sodium-ion batteries, the
      Prussian blue analogues all show a reversible capacity of 65 mA h g-1 at low
      current rate and show excellent cycle stability. The reported method stands as an
      environmentally friendly and low-cost alternative to hard or soft templating for
      the fabrication of mesoporous materials.

PMID- 24677673
TI  - Hazardous effects of sanguinarine on maturation of mouse oocytes, fertilization,
      and fetal development through apoptotic processes.
AB  - Previously, we reported that sanguinarine, a phytoalexin with antimicrobial, anti
      oxidant, anti-inflammatory and pro-apoptotic effects, is a risk factor for normal
      embryonic development that triggers apoptotic processes in the inner cell mass of
      mouse blastocysts, causing decreased embryonic development and cell viability. In
      the current study, we investigated the deleterious effects of sanguinarine on
      mouse oocyte maturation, in vitro fertilization (IVF), and subsequent pre- and
      postimplantation development both in vitro and in vivo. Notably, sanguinarine
      significantly impaired mouse oocyte maturation, decreased IVF rates, and
      inhibited subsequent embryonic development in vitro. Preincubation of oocytes
      with sanguinarine during in vitro maturation induced an increase in
      postimplantation embryo resorption and a decrease in mouse fetal weight. In an in
      vivo animal model, 1 to 5 MUM sanguinarine, provided in drinking water, caused a
      decrease in oocyte maturation and IVF, and led to deleterious effects on early
      embryonic development. Importantly, preincubation of oocytes with a caspase-3
      specific inhibitor effectively blocked sanguinarine-triggered deleterious
      effects, clearly implying that embryonic injury induced by sanguinarine is
      mediated by a caspase-dependent apoptotic mechanism.

PMID- 24677674
TI  - Restoration of portal flow using a pericholedochal varix in adult living donor
      liver transplantation for patients with total portosplenomesenteric thrombosis.
AB  - In total portosplenomesenteric thrombosis patients, cavoportal hemitransposition
      (CPHT) is indicated but rarely applicable for adult-to-adult (A-to-A) living
      donor liver transplantation (LDLT) because partial liver graft requires splanchno
      portal inflow for liver graft regeneration. If intra- & peri-pancreatic
      collaterals draining into pericholedochal varix were present, pericholedochal
      varix may provide splanchnic blood flow to the transplanted liver and also
      relieve recipient's portal hypertension. To date, however, there is no successful
      report using pericholedochal varix in liver transplantation (LT). We successfully
      performed A-to-A LDLTs using pericholedochal varix for those 2 patients. The
      surgical strategies are followings: (a) dissection of hepatic hilum to isolate
      left hepatic artery using for arterial reconstruction of implanted right lobe
      graft, (b) en-mass clamping of the undissected remaining hilum if we can leave
      adequate length of stump from the clamping site, and then hilum is divided, (c)
      delay the donor hepatectomy until the feasibility of the recipient operation is
      confirmed. Portal flow was established between the sizable pericholedochal varix
      (caliber > 1cm) and graft portal vein, but the individually designed approaches
      were used for each patients. Currently, they have been enjoying normal life on
      posttransplant 92 and 44 months respectively. In conclusion, enlarged
      pericholedochal varix in patients with totally obliterated splanchnic veins might
      be an useful inflow to restore portal flow and secure good outcome in A-to-A
      LDLT. AASLD.

PMID- 24677675
TI  - Prenatal diagnosis of proximal partial trisomy 1q confirmed by comparative
      genomic hybridization array: molecular cytogenetic analysis, fetal pathology and
      review of the literature.
AB  - BACKGROUND: Partial trisomy of the long arm of chromosome 1 (1q) is an
      exceptionally rare chromosomal abnormality and most of the prenatally diagnosed
      cases are associated with either complete (q11-qter) or large (q21-qter)
      duplications with pre- or perinatal demise of all reported cases. The most common
      sonographic findings associated with this karyotype abnormality include
      ventriculomegaly, increased nuchal translucency or nuchal fold, renal and cardiac
      abnormalities, craniofacial dysmorphism, and limb deformities. However, there is
      a wide spectrum of clinical manifestations due to the great variability in the
      extent of the duplication size and the possible contribution of additional
      genetic rearrangements in the final phenotype. CASE REPORT: We report on a female
      fetus with sole partial trisomy 1q presenting with multiple structural
      malformations in the second trimester scan. Standard karyotyping demonstrated a
      large duplication on the proximal end of chromosome 1 [46,XX,dup(1)(pter
      >q31::q31->q12::q31->qter)] and further application of comparative genomic
      hybridization array confirmed the diagnosis and offered a precise
      characterization of the genetic defect. CONCLUSION: A fetus with nonmosaic
      partial trisomy 1q that was prenatally diagnosed upon multiple abnormal
      ultrasound findings is presented. A detailed review of the currently available
      literature on the prenatal diagnostic approach of partial trisomy 1q in terms of
      fetal sonographic assessment and molecular cytogenetic investigation is also
      provided. The use of novel molecular techniques such comparative genomic
      hybridization array could shed further light on the correlation between the genes
      identified in the chromosomal region of interest and the resultant phenotype.

PMID- 24677676
TI  - Determination of flavor enhancers in milk powder by one-step sample preparation
      and two-dimensional liquid chromatography.
AB  - Maltol, ethyl maltol, vanillin, and ethyl vanillin are important food additives
      as flavor enhancers. To quantify the four additives in milk powder, a novel 2D
      liquid chromatographic (2DLC) method was developed in this article. In such a
      2DLC system, the target fractions eluted from the first dimensional column (C4)
      are stored onto the trapping column (C8) for subsequent analysis; after that,
      they were switched into the second dimensional column (C18) by a two-position six
      port switching valve. A one-step sample preparation method was used prior to 2DLC
      chromatographic analysis, which was easy and convenient. After optimization of
      all experimental parameters, the new method was validated in terms of linearity,
      LODs, and LOQs, intra- and interday precision, and accuracy. A conventional
      single-dimensional liquid chromatographic method was also proposed in this work
      for comparison. In order to evaluate the applicability of the new 2DLC method,
      five brands of commercial milk powder samples (n = 8) were analyzed. Vanillin and
      ethyl vanillin were detected in two samples, respectively. It is showed that the
      2DLC method is effective in quality control programs of milk powder products.

PMID- 24677670
TI  - Cathepsin B: multiple roles in cancer.
AB  - Proteases, including intracellular proteases, play roles at many different stages
      of malignant progression. Our focus here is cathepsin B, a lysosomal cysteine
      cathepsin. High levels of cathepsin B are found in a wide variety of human
      cancers, levels that often induce secretion and association of cathepsin B with
      the tumor cell membrane. In experimental models, such as transgenic models of
      murine pancreatic and mammary carcinomas, causal roles for cathepsin B have been
      demonstrated in initiation, growth/tumor cell proliferation, angiogenesis,
      invasion, and metastasis. Tumor growth in transgenic models is promoted by
      cathepsin B in tumor-associated cells, for example, tumor-associated macrophages,
      as well as in tumor cells. In transgenic models, the absence of cathepsin B has
      been associated with enhanced apoptosis, yet cathepsin B also has been shown to
      contribute to apoptosis. Cathepsin B is part of a proteolytic pathway identified
      in xenograft models of human glioma; targeting only cathepsin B in these tumors
      is less effective than targeting cathepsin B in combination with other proteases
      or protease receptors. Understanding the mechanisms responsible for increased
      expression of cathepsin B in tumors and association of cathepsin B with tumor
      cell membranes is needed to determine whether targeting cathepsin B could be of
      therapeutic benefit. 

PMID- 24677677
TI  - Chemistry in Israel--at a crossroads?

PMID- 24677678
TI  - Inpatient safety outcomes following the 2011 residency work-hour reform.
AB  - BACKGROUND: The impact of the 2011 residency work-hour reforms on patient safety
      is not known. OBJECTIVE: To evaluate the association between implementation of
      the 2011 reforms and patient safety outcomes at a large academic medical center.
      DESIGN: Observational study using difference-in-differences estimation strategy
      to evaluate whether safety outcomes improved among patients discharged from
      resident and hospitalist (nonresident) services before (2008-2011) and after
      (2011-2012) residency work-hour changes. PATIENTS: All adult patients discharged
      from general medicine services from July 2008 through June 2012. MEASUREMENTS:
      Outcomes evaluated included length of stay, 30-day readmission, intensive care
      unit (ICU) admission, inpatient mortality, and presence of Maryland Hospital
      Acquired Conditions. Independent variables included time period (pre- vs
      postreform), resident versus hospitalist service, patient age at admission, race,
      gender, and case mix index. RESULTS: Patients discharged from the resident
      services in the postreform period had higher likelihood of an ICU stay (5.7% vs
      4.5%, difference 1.4%; 95% confidence interval [CI]: 0.5% to 2.2%), and lower
      likelihood of 30-day readmission (17.2% vs 20.1%, difference 2.8%; 95 % CI: 1.3
      to 4.3%) than patients discharged from the resident services in the prereform
      period. Comparing pre- and postreform periods on the resident and hospitalist
      services, there were no significant differences in patient safety outcomes.
      CONCLUSIONS: In the first year after implementation of the 2011 work-hour reforms
      relative to prior years, we found no change in patient safety outcomes in
      patients treated by residents compared with patients treated by hospitalists.
      Further study of the long-term impact of residency work-hour reforms is indicated
      to ensure improvement in patient safety.

PMID- 24677679
TI  - Balancing the initiation and molecular recognition capabilities of eosin
      macroinitiators of polymerization-based signal amplification reactions.
AB  - Coupling polymerization initiators to molecular recognition events provide the
      ability to amplify these events and detect them using the formation of a cross
      linked polymer as an inexpensive readout that is visible to the unaided eye. The
      eosin-tertiary amine co-initiation system, activated by visible light, has proven
      utility in this context when an average of three eosin molecules are coupled to a
      protein detection reagent. The present work addresses the question of how
      detection sensitivity is impacted when the number of eosin molecules per binding
      event increases in the range of two to fifteen. Unlike in other initiation
      systems, a non-monotonic relationship is observed between the number of
      initiators per binding event and the observed detection sensitivity. 

PMID- 24677680
TI  - Mood-stabilizers differentially affect housekeeping gene expression in human
      cells.
AB  - Recent studies have revealed that antidepressants affect the expression of
      constitutively expressed "housekeeping genes" commonly used as normalizing
      reference genes in quantitative polymerase chain reaction (qPCR) experiments.
      There has yet to be an investigation however on the effects of mood-stabilizers
      on housekeeping gene stability. The current study utilized lymphoblastoid cell
      lines (LCLs) derived from patients with mood disorders to investigate the effects
      of a range of doses of lithium (0, 1, 2 and 5 mM) and sodium valproate (0, 0.06,
      0.03 and 0.6 mM) on the stability of 12 housekeeping genes. RNA was extracted
      from LCLs and qPCR was used to generate cycle threshold (Ct ) values which were
      input into RefFinder analyses. The study revealed drug-specific effects on
      housekeeping gene stability. The most stable housekeeping genes in LCLs treated:
      acutely with sodium valproate were ACTB and RPL13A; acutely with lithium were
      GAPDH and ATP5B; chronically with lithium were ATP5B and CYC1. The stability of
      GAPDH and B2M were particularly affected by duration of lithium treatment. The
      study adds to a growing literature that the selection of appropriate housekeeping
      genes is important for the accurate normalization of target gene expression in
      experiments investigating the molecular effects of mood disorder
      pharmacotherapies.

PMID- 24677681
TI  - Detachment of mesenchymal stem cells with trypsin/EDTA has no effect on apoptosis
      detection.

PMID- 24677682
TI  - Amidines for versatile ruthenium(II)-catalyzed oxidative C-H activations with
      internal alkynes and acrylates.
AB  - Cationic ruthenium complexes derived from KPF6 or AgOAc enabled efficient
      oxidative C?H functionalizations on aryl and heteroaryl amidines. Thus, oxidative
      annulations of diversely decorated internal alkynes provided expedient access to
      1-aminoisoquinolines, while catalyzed C-H activations with substituted acrylates
      gave rise to structurally novel 1-iminoisoindolines. The powerful ruthenium(II)
      catalysts displayed a remarkably high site-, regio- and, chemoselectivity.
      Therefore, the catalytic system proved tolerant of a variety of important
      electrophilic functional groups. Detailed mechanistic studies provided strong
      support for the cationic ruthenium(II) catalysts to operate by a facile,
      reversible C-H activation.

PMID- 24677684
TI  - Motivational dimensions of inpatient aggression.
AB  - BACKGROUND: Recent studies have suggested that functional classifications of
      aggression should be used to improve the understanding of the heterogeneity of
      aggression and its management, among inpatients in psychiatric hospitals. AIMS:
      Our aim was to examine a theoretically derived three-factor model for
      conceptualising aggressive incidents by inpatients as irritable, instrumental or
      defensive. METHODS: As part of the routine assessments in a forensic psychiatric
      high security ward, staff filled out a questionnaire on motives for aggression
      after all violent incidents. A total of 1652 incidents from 28 patients were
      analysed by means of exploratory and confirmatory factor analyses. RESULTS:
      Support was found for the three-factor model. For the most part, the scale items
      loaded on the factors as predicted, and the model was able to explain 61% of the
      data variance. Irritable incidents were the most common, but elevated scores for
      instrumental characteristics were found as well. High psychopathy scores were
      associated with incidents scoring high values on both irritable and instrumental
      dimensions, and low values on the defensive dimensions. CONCLUSIONS: Confirming
      these three dimensions of inpatient aggressive incidents may help caregivers'
      understanding of aggressive behaviour. If confirmed in future studies, this
      dimensional approach may prove useful for the management of aggressive
      inpatients.

PMID- 24677685
TI  - Copulation without seminal expulsion: the consequence of sexual satiation and the
      Coolidge effect.
AB  - The studies of sexual satiety in male rats under the Coolidge effect indicate
      that males reassume copulation until ejaculation. Recently, it was demonstrated
      that sexually satiated males preserve the motor patterns of intromission and
      ejaculation, also penile erection, but not seminal expulsion. The first aim was
      to investigate if penile erections displayed by sexually satiated males dislodge
      the seminal plugs from the vagina and its effect on sperm transcervical
      transport. The second aim was to determine the recovery time of seminal expulsion
      after sexual satiety and its optimal ability to induce pregnancy. Results show
      that during the Coolidge effect males were able to dislodge the seminal plugs
      deposited by others (experiment 1A) disturbing the sperm transport (experiment
      1B) then interfering with pregnancy (experiment 1C). After satiation, the
      ejaculate parameters recover slowly: it starts after 10 days with the seminal
      plug formation, and continues with an increase in sperm count in the uterus 15
      days post-satiety (experiment 2). Sexually satiated males impregnated only 28% of
      the females during 15 days of cohabitation, whereas, satiated males that rested
      for 15 days impregnated 89% of the females (experiment 3). We concluded that
      males with successive ejaculations remain potential rivals, because they may
      disrupt the sperm transport of other males. The ejaculate features recovery after
      sexual satiety is gradual, begins with the secretions of the sex accessory glands
      and is followed by the sperm count. Full fertility recovery is reached after 15
      days of sexual abstinence when males are able to impregnate most females.

PMID- 24677683
TI  - Toward a symphony of reactivity: cascades involving catalysis and sigmatropic
      rearrangements.
AB  - Catalysis and synthesis are intimately linked in modern organic chemistry. The
      synthesis of complex molecules is an ever evolving area of science. In many
      regards, the inherent beauty associated with a synthetic sequence can be linked
      to a certain combination of the creativity with which a sequence is designed and
      the overall efficiency with which the ultimate process is performed. In
      synthesis, as in other endeavors, beauty is very much in the eyes of the
      beholder. It is with this in mind that we will attempt to review an area of
      synthesis that has fascinated us and that we find extraordinarily beautiful,
      namely the combination of catalysis and sigmatropic rearrangements in consecutive
      and cascade sequences.

PMID- 24677686
TI  - Pulse wave velocity and flow in the carotid artery versus the aortic arch:
      effects of aging.
AB  - PURPOSE: To explore differences in arterial stiffness of the aorta and carotid
      artery, assessed by pulse wave velocity (PWV), to evaluate the blood flow volume
      distribution towards the carotid circulation and to assess the effect of aging on
      the coupling between aortic and carotid PWV using velocity-encoded magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: Sixteen adult younger volunteers
      (age <30 years) and 16 older volunteers (age >45 years) underwent 3T MRI
      examination to assess aortic and carotid flow volumes and PWV using the transit
      time method. RESULTS: Aortic versus carotid PWV-ratio was 1.2 for younger
      volunteers and 0.95 for older volunteers, demonstrating leveling of wall
      stiffness. Furthermore, flow volume per minute in the internal carotid artery was
      lower for older versus younger volunteers (mean volume 177 +/- 42 mL/min/m(2) vs.
      147 +/- 32 mL/min/m(2), P = 0.028), whereas aorta and common carotid artery flow
      volumes were not different. Consequently, the fraction of blood flow volume
      towards the brain was smaller for older versus younger volunteers (61 +/- 9%
      versus 71 +/- 8%, P = 0.002). CONCLUSION: PWV-leveling between aorta and carotid
      artery at older age is associated with a reduction in blood flow volume towards
      the brain. Velocity-encoded MRI can be used to evaluate PWV and flow volume
      distribution in the aortic arch and the carotid circulation.

PMID- 24677690
TI  - Geometrical isomerism of Ru(II) dye-sensitized solar cell sensitizers and effects
      on photophysical properties and device performances.
AB  - To supplement our study on thiocyanate-free ruthenium sensitizers (TFRS) for dye
      sensitized solar cells (DSSCs), which belong to a class of Ru(II)-based complexes
      coordinated by a single 4,4'-dicarboxylic acid-2,2'-bipyridine and two
      symmetrically arranged functionalized trans-azolate chelates, we carefully
      isolated and characterized the second and less-abundant stereoisomer, in which
      the two pyridyl azolate ancillaries are asymetrically cis-arranged to each other.
      Two distinctive ancillaries, namely: 5-[4-(5-hexyl-2-thienyl)-2-pyridinyl]-3
      trifluoromethyl pyrazole and 5-(6-tert-butyl-1-isoquinolinyl)-3-trifluoromethyl
      pyrazole, were employed in this study, giving a total of four sensitizers, that
      is, thienyl substituted TFRS-2 a and 2 b, and isoquinolinyl substituted TFRS-52 a
      and 52 b, in which the suffix b indicates the cis-stereoisomers. To gain insight
      into their fundamental properties their photophysical, electrochemical, and
      spectroelectrochemical behavior was investigated by density functional theory.
      Upon comparison of the correspondingly fabricated DSSCs, the sensitizers TFRS-2 a
      and 52 a yielded significantly higher conversion efficiencies than their
      asymmetrical cis-counterparts, TFRS-2 b and 52 b. To rationalize the cell
      performances charge extraction/photovoltage decay and impedance spectroscopic
      measurements were carried out to compare the rates of interfacial electron
      recombination from the TiO2 conduction band to the electrolyte.

PMID- 24677687
TI  - In search of antiaging modalities: evaluation of mTOR- and ROS/DNA damage
      signaling by cytometry.
AB  - This review presents the evidence in support of the IGF-1/mTOR/S6K1 signaling as
      the primary factor contributing to aging and cellular senescence. Reviewed are
      also specific interactions between mTOR/S6K1 and ROS-DNA damage signaling
      pathways. Outlined are critical sites along these pathways, including autophagy,
      as targets for potential antiaging (gero-suppressive) and/or chemopreventive
      agents. Presented are applications of flow- and laser scanning- cytometry
      utilizing phospho-specific Abs, to monitor activation along these pathways in
      response to the reported antiaging drugs rapamycin, metformin, berberine,
      resveratrol, vitamin D3, 2-deoxyglucose, and acetylsalicylic acid. Specifically,
      effectiveness of these agents to attenuate the level of constitutive mTOR
      signaling was tested by cytometry and confirmed by Western blotting through
      measuring phosphorylation of the mTOR-downstream targets including ribosomal
      protein S6. The ratiometric analysis of phosphorylated to total protein along the
      mTOR pathway offers a useful parameter reporting the effects of gero-suppressive
      agents. In parallel, their ability to suppress the level of constitutive DNA
      damage signaling induced by endogenous ROS was measured. While the primary target
      of each of these agents may be different the data obtained on several human
      cancer cell lines, WI-38 fibroblasts and normal lymphocytes suggest common
      downstream mechanism in which the decline in mTOR/S6K1 signaling and translation
      rate is coupled with a reduction of oxidative phosphorylation and ROS that leads
      to decreased oxidative DNA damage. The combined assessment of constitutive
      gammaH2AX expression, mitochondrial activity (ROS, DeltaPsim), and mTOR signaling
      provides an adequate gamut of cell responses to test effectiveness of gero
      suppressive agents. Described is also an in vitro model of induction of cellular
      senescence by persistent replication stress, its quantitative analysis by laser
      scanning cytometry, and application to detect the property of the studied agents
      to attenuate the induction of senescence. Discussed is cytometric analysis of
      cell size and heterogeneity of size as a potential biomarker used to asses gero
      suppressive agents and longevity.

PMID- 24677689
TI  - Interatrial pressure gradients during simulated obstructive sleep apnea: a
      catheter-based study.
AB  - OBJECTIVES: We set to measure the interatrial pressure gradient during simulated
      obstructive sleep apnea (OSA). BACKGROUND: OSA occurs when a sleeping patient
      attempts to inhale against an obstructed airway. How this event affects the
      interatrial pressure gradient has not been defined. We hypothesized that
      simulated OSA in a conscious subject (Mueller maneuver [MM], inspiration against
      obstruction) would promote increased right-to-left pressure gradient, and then
      the substrate for right-to-left atrial shunting. METHODS: Selected patients
      underwent simultaneous measurement of airway and atrial pressures (both left and
      right atrium [LA, RA]) using high-fidelity micromanometry at rest, during MM, and
      during VM, during right heart catheterization. RESULTS: Ten patients (age 55 +/-
      11 years, two women) were successfully studied. During the onset of MM, RA
      pressure transiently but consistently exceeded LA pressure in response to the
      steep decline in intrathoracic pressure (maximum RA-LA pressure gradient
      increased from 0.1 +/- 1.4 mm Hg at baseline to 7.0 +/- 4.3 mm Hg during MM, P <
      0.001). The maximum right-to-left atrial pressure gradient during Mueller
      maneuver was higher than that achieved during the Valsalva maneuver release (P <
      0.007). CONCLUSIONS: The onset of MM increased right-to-left pressure gradient
      across the atrial septum, likely as a result of greater blood return to the RA
      from extrathoracic veins. The RA-LA pressure gradient achieved during MM was
      greater than that observed during VM. These findings delineate the hemodynamic
      substrate for right to left shunting during OSA.

PMID- 24677688
TI  - Correlates and variance decomposition analysis of heparin dosing for maintenance
      hemodialysis in older US patients.
AB  - PURPOSE: Heparin is commonly used to anticoagulate the hemodialysis (HD) circuit.
      Despite the bleeding risk, no American standards exist for its administration. We
      identified correlates and quantified sources of variance in heparin dosing for
      HD. METHODS: We performed a cross-sectional study of patients aged 67 years or
      older who underwent HD with heparin on one of two randomly chosen days in 2008 at
      a national chain of dialysis facilities. Using a mixed effects model with random
      intercept for facility and fixed patient and facility characteristics, we
      examined heparin dosing at patient and facility levels. RESULTS: The median
      heparin dose among the 17 722 patients treated in 1366 facilities was 4000 (25th
      75th percentile: 2625-6000) units. In multivariable-adjusted analyses, higher
      weight, longer session duration, catheter use, and dialyzer reuse were
      significantly associated with higher heparin dose. Dose also varied considerably
      among census divisions. Of the overall variance in dose, 21% was due to between
      facility differences, independent of facilities' case mix, geography, size, or
      rurality; 79% was due to differences at the patient level. The patient and
      facility characteristics in our model explained only 25% of the variance at the
      patient level. CONCLUSIONS: Despite the lack of standards for heparin
      administration, we noted patterns of use, including weight-based and time
      dependent dosing. Most of the variance was at the patient level; however, only a
      quarter of it could be explained. The high amount of unexplained variance
      suggests that factors other than clinical need are driving heparin dosing and
      that there is likely room for more judicious dosing of heparin.

PMID- 24677691
TI  - Natural products - learning chemistry from plants.
AB  - Plant natural products (PNPs) are unique in that they represent a vast array of
      different structural features, ranging from relatively simple molecules to very
      complex ones. Given the fact that many plant secondary metabolites exhibit
      profound biological activity, they are frequently used as fragrances and flavors,
      medicines, as well as industrial chemicals. As the intricate structures of PNPs
      often cannot be mimicked by chemical synthesis, the original plant providers
      constitute the sole source for their industrial, large-scale production. However,
      sufficient supply is not guaranteed for all molecules of interest, making the
      development of alternative production systems a priority. Modern techniques, such
      as genome mining and thorough biochemical analysis, have helped us gain
      preliminary understanding of the enzymatic formation of the valuable ingredients
      in planta. Herein, we review recent advances in the application of biocatalytical
      processes, facilitating generation of complex PNPs through utilization of plant
      derived specific enzymes and combinatorial biochemistry. We further evaluate the
      options of employing heterologous organisms harboring PNP biosynthetic pathways
      for the production of secondary metabolites of interest.

PMID- 24677693
TI  - Hyperphosphorylation of microfilament-associated proteins is involved in
      microcystin-LR-induced toxicity in HL7702 cells.
AB  - Microcystin-LR (MC-LR) has been regarded as a hepatotoxin, which can cause
      cytoskeletal reorganization, especially of the actin filaments. However, the
      underlying mechanisms remain unclear. In this study, whether MC-LR could induce
      microfilaments disruption was verified in the normal human liver cell line
      HL7702; and then the transcription, translation, and phosphorylation levels of
      major microfilament-associated proteins were measured; finally, the underlying
      mechanisms was investigated. After treatment with MC-LR, the actin filaments lost
      their characteristic filamentous organization in the cells, demonstrating
      increased actin depolymerization. The mRNA and protein levels of ezrin,
      vasodilator-stimulated phosphoprotein (VASP), actin-related protein2/3, and
      cofilin remained unchanged. However, the phosphorylation levels of ezrin and VASP
      were increased, when treated with 10 MUM MC-LR. Moreover, P38 and ERK1/2 were
      involved in MC-LR-induced hyperphosphorylation of microfilament-associated
      proteins. In summary, this study demonstrates that MC-LR can cause disruption of
      actin filaments in HL7702 cells due to MC-LR-induced mitogen-activated protein
      kinase pathway activation and hyperphosphorylation of different types of
      microfilament-associated proteins.

PMID- 24677694
TI  - Blessing or curse? Proteomics in granzyme research.
AB  - Granzymes (gzms) are a group of serine proteases that play an important role in
      innate and adaptive immunity, blood coagulation, apoptosis, and inflammation, but
      are also connected to atherosclerosis, diabetes, cardiovascular and inflammatory
      lung diseases, cancer, and sepsis. Humans have five gzms (gzms A, B, H, K, and
      M), which differ in their substrate specificity. It is widely accepted that they
      are delivered from cytotoxic lymphocytes via perforin into the cytoplasm of
      target cells where they initiate cell death, modulate cytokine signaling, or
      inactivate pathogen proteins. However, more recent evidence indicates gzms also
      act extracellularly in noncytotoxic processes. Proteomic approaches are directed
      at mapping gzm cleavage specificity, identifying substrates, and unraveling the
      (patho-) physiological role of these proteases. These studies have refined our
      understanding of gzm species specificity, and collectively uncovered an enormous
      number of new substrates. However, with the exception of a very few human gzmB
      substrates supported by independent data (Bid, DNA-PK, PARP, ICAD, and procaspase
      7), it is presently unclear which are physiologically relevant. This review aims
      to summarize and analyze the different proteomic approaches used and discuss both
      their convincing and controversial outcomes. 

PMID- 24677692
TI  - Discovery of 5-(2-(phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one derivatives as
      potent Mnk2 inhibitors: synthesis, SAR analysis and biological evaluation.
AB  - Phosphorylation of eIF4E by human mitogen-activated protein kinase (MAPK)
      interacting kinases (Mnks) is crucial for human tumourigenesis and development.
      Targeting Mnks may provide a novel anticancer therapeutic strategy. However, the
      lack of selective Mnk inhibitors has so far hampered pharmacological target
      validation and clinical drug development. Herein, we report, for the first time,
      the discovery of a series of 5-(2-(phenylamino)pyrimidin-4-yl)thiazole-2(3H)-one
      derivatives as Mnk inhibitors. Several derivatives demonstrate very potent Mnk2
      inhibitory activity. The most active and selective compounds were tested against
      a panel of cancer cell lines, and the results confirm the cell-type-specific
      effect of these Mnk inhibitors. Detailed cellular mechanistic studies reveal that
      Mnk inhibitors are capable of reducing the expression level of anti-apoptotic
      protein Mcl-1, and of promoting apoptosis in MV4-11 acute myeloid leukaemia
      cells. 

PMID- 24677695
TI  - US doctors earn speaking and consulting fees from drug companies that sponsor
      their research.

PMID- 24677696
TI  - Rare nasal cleft in a patient with holoprosencephaly due to a mutation in the
      ZIC2 gene.
AB  - BACKGROUND: Holoprosencephaly (HPE) is a spectrum of midline malformations of the
      prosencephalon generally reflected in a continuum of midline facial anomalies.
      Patients with mutation in the ZIC2 gene usually present a normal or mildly
      dysmorphic face associated with a severe brain malformation. Here we present a
      rare unilateral nasal cleft (Tessier cleft n. 1) with holoprosencephaly in a
      patient with a ZIC2 mutation. CASE: The male newborn presented with alobar HPE,
      microcephaly, ocular hypertelorism, upslanting palpebral fissures, a bulky nose
      with a left paramedian alar cleft. Mutational screening for HPE genes revealed
      the occurrence of a frameshift mutation in the ZIC2 gene. The mutation was
      inherited from the father who presented only mild ocular hypotelorism but had an
      affected child with HPE from his first marriage. CONCLUSION: The occurrence of
      oral clefts is common in patients with HPE, but unusual in patients with mutation
      in the ZIC2 gene. To our knowledge, clefts of the nasal alae have been reported
      only once or twice in patients with ZIC2 mutations. In documented patients from
      the literature, only 2% of individuals with described pathogenic mutations in the
      ZIC2 gene (3/171) presented facial clefts, one of them a nasal cleft, while
      common oral clefts were observed in 27% of individuals (7/26) described with
      nonpathogenic ZIC2 mutations or presenting a concomitant mutation in another HPE
      gene. When compared with the general population, nasal clefts are common in ZIC2
      mutations and these mutations must be searched for in undiagnosed cases.

PMID- 24677697
TI  - Late-stage functionalization of biologically active heterocycles through
      photoredox catalysis.
AB  - The direct C?H functionalization of heterocycles has become an increasingly
      valuable tool in modern drug discovery. However, the introduction of small alkyl
      groups, such as methyl, by this method has not been realized in the context of
      complex molecule synthesis since existing methods rely on the use of strong
      oxidants and elevated temperatures to generate the requisite radical species.
      Herein, we report the use of stable organic peroxides activated by visible-light
      photoredox catalysis to achieve the direct methyl-, ethyl-, and cyclopropylation
      of a variety of biologically active heterocycles. The simple protocol, mild
      reaction conditions, and unique tolerability of this method make it an important
      tool for drug discovery. 

PMID- 24677698
TI  - Metabolomics study of cured tobacco using liquid chromatography with mass
      spectrometry: method development and its application in investigating the
      chemical differences of tobacco from three growing regions.
AB  - Cured tobacco is an important plant material. Component studies are a big
      challenge for its significantly diverse chemical properties and vastly different
      concentrations. In this work, liquid chromatography with quadrupole time-of
      flight mass spectrometry was used to perform a metabolomics study of cured
      tobacco owing to its efficient separation and detection of semipolar metabolites.
      A solvent of methanol/water (8:2, v/v) and 30 min of ultrasound time were found
      to be optimal to perform extraction. 95, 92, and 93% of metabolite features had
      within 20% of coefficient of variation for repeatability, intraday and interday
      precision analysis, respectively, indicating a good stability of the method
      developed. 113 metabolites were identified in cured tobacco based on accurate
      mass, retention time, and MS/MS fragments. The developed method was applied to a
      metabolomics study of cured tobacco from three growing regions. Forty three
      metabolites were found to be contributed to the classification. It is shown that
      the developed method can be applied to metabolomics analysis of plant materials. 

PMID- 24677699
TI  - One-year test-retest reliability of a Japanese web-based version of the WHO
      Composite International Diagnostic Interview (CIDI) for major depression in a
      working population.
AB  - The purpose of this study was to investigate the one-year test-retest reliability
      and the demographic correlates of a self-administered web-based depression
      section of the World Health Organization-Composite International Diagnostic
      Interview (WHO-CIDI) in a working population. Overall, 1060 out of all employees
      (N = 1279) from a manufacturing company in Japan responded to two web-based
      surveys of depression of the WHO-CIDI within a one-year interval in 2009 and
      2010. The concordance between lifetime diagnoses of major depressive disorder on
      two occasions was calculated as percent agreement (%), Gwet's AC1 , and Yule's Q
      indicators were compared by gender, age, education, and marital status. For the
      total sample, percent agreement was 94%, AC1 was 0.93, and Yule's Q was 0.82. The
      concordance rate was low (0.15) among those who were diagnosed at either time or
      both times. The concordance differed significantly across education and marital
      status. While the agreement indicators were relatively high, consistent with
      previous reports based on face-to-face interviews conducted within a shorter
      interval, the low stability of positive cases may challenge the accuracy of
      lifetime diagnosis of major depressive disorder using a web version of the WHO
      CIDI. Education and marital status might affect the test-retest reliability.
      Copyright (c) 2014 John Wiley & Sons, Ltd. 

PMID- 24677700
TI  - Mafia and psychopathy.
AB  - BACKGROUND: In popular culture, Mafia members are often portrayed as ruthless,
      callous and remorseless, but there is no empirical research on their personality
      traits. AIMS: The goal of this research was to examine levels of psychopathic
      traits among Mafia members who have been convicted of a criminal offence.
      METHODS: The Psychopathy Checklist-Revised (PCL-R) rated 30 Italian adult male
      prisoners who had been convicted for Mafia-related crimes (86% resident in one 6
      month period) and 39 next adjacent convicted men who were not enrolled in any
      criminal organisation. RESULTS: Mafia members obtained lower PCL-R total scores,
      interpersonal and affective (PCL-R factor 1) scores and lifestyle scores (factor
      2) than the other offenders. Logistic regression analysis showed that lower PCL-R
      factor 1 scores with higher factor 2 scores in the absence of a history of
      substance misuse disorder distinguished Mafia from non-Mafia offenders. A
      probability curve confirmed an exponential growth in the probability of
      classification as a Mafia member in relation to lower PCL-R factor 1 scores.
      CONCLUSIONS: Our findings bring new hope for resocialisation of convicted Mafia
      members, because they showed significant antisocial traits but they maintained a
      capacity for emotional connection and greater likelihood of engaging with
      training and resocialisation programmes than other imprisoned offenders in Italy.

PMID- 24677701
TI  - Metal-free C-C coupling reactions with tetraguanidino-functionalized pyridines
      and light.
AB  - Herein we report on metal-free C-C coupling reactions mediated by the pyridine
      derivative 2,3,6,7-tetrakis(tetramethylguanidino)pyridine under the action of
      visible light. The rate-determining step is the homolytic N-C bond cleavage of
      the initially formed N-alkyl pyridinium ion upon excitation with visible light.
      The released alkyl radicals subsequently dimerize to the C-C coupling product.
      2,3,6,7-Tetrakis(tetramethylguanidino)pyridine, which is a strong electron donor
      (E1/2(CH2Cl2) = -0.76 V vs. ferrocene) is oxidized to the dication. For alkyl =
      benzyl and allyl, relatively high first-order rate constants of 0.23+/-0.03 and
      0.13+/-0.03 s(-1) were determined. Regeneration of neutral 2,3,6,7
      tetrakis(tetramethylguanidino)-pyridine by reduction allows to drive the process
      in a cycle.

PMID- 24677702
TI  - Obesity, central adiposity and cardiometabolic risk factors in children and
      adolescents: a family-based study.
AB  - OBJECTIVE: The objective of this study was to assess genetic and phenotypic
      correlations of obesity-related cardiometabolic risk factors in a family-based
      cohort. METHODS: Anthropometric, body composition and biochemical measurements
      were collected on 999 members of 111 extended Midwestern US families of Northern
      European origin. Forward stepwise regression was used to identify which of Tanner
      stage, sex, Tanner stage by sex, body fat mass index, body fat percentage (dual
      energy X-ray absorptiometry), visceral fat (VF)/subcutaneous fat (SubQF)
      (computed tomography scans for adults or magnetic resonance imaging for
      children), VF, SubQF, body mass index (BMI)% and waist to height ratio most
      influence homeostasis model assessment (HOMA), high-density lipoprotein
      cholesterol (HDL-c), plasma triglycerides (TG) and low-density lipoprotein
      cholesterol (LDL-c). RESULTS: In children and adolescents, subcutaneous adiposity
      was the most significant covariate for HOMA (P < 0.001) and TG (P = 0.001), and
      BMI percentile for HDL-c (P = 0.002) and LDL-c (P < 0.001). In adults, waist
      height ratio (P < 0.001), VF/SubQF ratio (P = 0.001) and BMI (P = 0.02) were most
      significant for HOMA; VF (P < 0.001) and BMI (P = 0.02) for TG and VF for LDL-c
      (P = 0.001). CONCLUSION: Subcutaneous adiposity at the waist is a more
      significant predictor of metabolic syndrome traits in children and adolescents
      than it is in adults.

PMID- 24677703
TI  - Critical role of Jak2 in the maintenance and function of adult hematopoietic stem
      cells.
AB  - Jak2, a member of the Janus kinase family of nonreceptor protein tyrosine
      kinases, is activated in response to a variety of cytokines, and functions in
      survival and proliferation of cells. An activating JAK2V617F mutation has been
      found in most patients with myeloproliferative neoplasms, and patients treated
      with Jak2 inhibitors show significant hematopoietic toxicities. However, the role
      of Jak2 in adult hematopoietic stem cells (HSCs) has not been clearly elucidated.
      Using a conditional Jak2 knockout allele, we have found that Jak2 deletion
      results in rapid loss of HSCs/progenitors leading to bone marrow failure and
      early lethality in adult mice. Jak2 deficiency causes marked impairment in HSC
      function, and the mutant HSCs are severely defective in reconstituting
      hematopoiesis in recipient animals. Jak2 deficiency also causes significant
      apoptosis and loss of quiescence in HSC-enriched LSK (Lin(-)Sca-1(+)c-Kit(+))
      cells. Jak2-deficient LSK cells exhibit elevated reactive oxygen species levels
      and enhanced p38 MAPK activation. Mutant LSK cells also show defective Stat5,
      Erk, and Akt activation in response to thrombopoietin and stem cell factor. Gene
      expression analysis reveals significant downregulation of genes related to HSC
      quiescence and self-renewal in Jak2-deficient LSK cells. These data suggest that
      Jak2 plays a critical role in the maintenance and function of adult HSCs.

PMID- 24677704
TI  - Immediate and short-term outcomes after percutaneous atrial septal defect closure
      using the new nit-occlud ASD-R device.
AB  - OBJECTIVES: To evaluate the feasibility, safety, and efficacy of implantation of
      the new Nit Occlud ASD-R(r) (NOASD-R) device for percutaneous closure of ostium
      secundum atrial septal defects (ASD-OS). BACKGROUND: Device catheter implantation
      has become the method of choice for most patients with ASD-OS. No single device
      has proven to be ideal for this type of procedure. The NOASD-R has a distinct
      design that may help to overcome limitations of other devices. METHODS: A
      prospective, single arm, observational study including all consecutive patients
      receiving the NOASD-R device for ASD-OS closure between October 2011 and
      September 2013 was performed. Patient selection, device design, deployment
      technique, complications, and procedural outcomes were evaluated. RESULTS:
      Seventy-four patients underwent attempted transcatheter ASD-OS closure using the
      NOASD-R device. Implantation of the occluder was successful in 73 patients
      (98.6%). The majority of patients were female (79.5%) with a median age of 17.2
      years (range: 2-74). A 2-D transthoracic color-Doppler echocardiogram (TTE)
      obtained at the 3 or 6 month follow-up visit showed complete occlusion of the ASD
      OS in 72/73 patients (98.6%). At a mean follow-up interval of 11.4 +/- 6.8 months
      there have been no episodes of late device embolization, cardiac perforation or
      erosion, endocarditis, thromboembolism, wire fracture, embolic neurologic events,
      or death. CONCLUSIONS: We report the first worldwide clinical experience using
      the NOASD-R device for ASD-OS closure. The procedure was feasible, with a high
      rate of successful implantations, and safe. High ASD-OS closure rates and no
      complications were encountered during short-term follow-up. (c) 2014 Wiley
      Periodicals, Inc.

PMID- 24677705
TI  - Bioglass(r)/chitosan-polycaprolactone bilayered composite scaffolds intended for
      osteochondral tissue engineering.
AB  - Polymer-coated 45S5 Bioglass((r)) (BG)/chitosan-polycaprolactone (BG/CS-PCL)
      bilayered composite scaffolds were prepared via foam replication and freeze
      drying techniques for application in osteochondral tissue engineering. The CS-PCL
      coated and uncoated BG scaffolds were characterized by X-ray diffraction (XRD),
      Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy
      (SEM). The mechanical properties of the coated scaffolds were significantly
      improved in comparison to uncoated scaffolds. The bioactivity and biodegradation
      behavior of scaffolds were studied in simulated body fluid (SBF) for up to 28
      days. The interface between the BG scaffold and the polymer coating layer was
      observed by SEM and a suitable interpenetration of the polymer into the scaffold
      struts was found. The effects of coated and uncoated BG scaffolds on MG-63
      osteoblast-like cells were evaluated by cell viability, adhesion and
      proliferation.

PMID- 24677707
TI  - Discontinuous thermal diffusivity change due to the anchoring transition of a
      liquid crystal on a perfluoropolymer surface.
AB  - Thermal diffusivity of a liquid crystal, 4'-butyl-4-heptyl-bicyclohexyl-4
      carbonitrile, was measured using a temperature wave method. The liquid crystal
      was sandwiched by two glass substrates, which were treated with three different
      surface agents for providing distinct molecular orientations. Here, we
      demonstrate that: 1) a large thermal diffusivity anisotropy arising from
      different orientations, that is, planar and homeotropic states, was found in the
      nematic and smectic A phases; 2) when substrates were coated with a
      perfluoropolymer, abrupt changes of the thermal diffusivity were observed in the
      nematic phase both on cooling and heating due to the discontinuous anchoring
      transition between planar and homeotropic states. The temperature dependence of
      the thermal diffusivity anisotropy was well described by a power law, with an
      exponent of 0.27 according to the mean-field theory. 

PMID- 24677706
TI  - Mechanisms of osteoarthritis in the knee: MR imaging appearance.
AB  - Osteoarthritis has grown to become a widely prevalent disease that has major
      implications in both individual and public health. Although originally considered
      to be a degenerative disease driven by "wear and tear" of the articular
      cartilage, recent evidence has led to a consensus that osteoarthritis
      pathophysiology should be perceived in the context of the entire joint and
      multiple tissues. MRI is becoming an increasingly more important modality for
      imaging osteoarthritis, due to its excellent soft tissue contrast and ability to
      acquire morphological and biochemical data. This review will describe the
      pathophysiology of osteoarthritis as it is associated with various tissue types,
      highlight several promising MR imaging techniques for osteoarthritis and
      illustrate the expected appearance of osteoarthritis with each technique.

PMID- 24677708
TI  - Synthesis and biological evaluation of 2-substituted-5-(4
      nitrophenylsulfonamido)benzoxazoles as human GST P1-1 inhibitors, and description
      of the binding site features.
AB  - Glutathione-S-transferases (GSTs) are enzymes involved in cellular detoxification
      by catalyzing the nucleophilic attack of glutathione (GSH) on the electrophilic
      center of numerous of toxic compounds and xenobiotics, including chemotherapeutic
      drugs. Human GST P1-1, which is known as the most prevalent isoform of the
      mammalian cytosolic GSTs, is overexpressed in many cancers and contributes to
      multidrug resistance by directly conjugating to chemotherapeutics. It is
      suggested that this resistance is related to the high expression of GST P1-1 in
      cancers, thereby contributing to resistance to chemotherapy. In addition, GSTs
      exhibit sulfonamidase activity, thereby catalyzing the GSH-mediated hydrolysis of
      sulfonamide bonds. Such reactions are of interest as potential tumor-directed
      prodrug activation strategies. Herein we report the design and synthesis of some
      novel sulfonamide-containing benzoxazoles, which are able to inhibit human GST P1
      1. Among the tested compounds, 2-(4-chlorobenzyl)-5-(4
      nitrophenylsulfonamido)benzoxazole (5 f) was found as the most active hGST P1-1
      inhibitor, with an IC50 value of 10.2 MUM, showing potency similar to that of the
      reference drug ethacrynic acid. Molecular docking studies performed with CDocker
      revealed that the newly synthesized 2-substituted-5-(4
      nitrophenylsulfonamido)benzoxazoles act as catalytic inhibitors of hGST P1-1 by
      binding to the H-site and generating conjugates with GSH to form S-(4
      nitrophenyl)GSH (GS-BN complex) via nucleophilic aromatic substitution reaction.
      The 4-nitrobenzenesulfonamido moiety at position 5 of the benzoxazole ring is
      essential for binding to the H-site and for the formation of the GST-mediated GSH
      conjugate.

PMID- 24677709
TI  - Crucial role of Notch signaling in osteogenic differentiation of periodontal
      ligament stem cells in osteoporotic rats.
AB  - Estrogen deficiency-induced osteoporosis typically occurs in postmenopausal women
      and has been strongly associated with periodontal diseases. Periodontal ligament
      stem cells (PDLSCs) isolated from the periodontal ligament can differentiate into
      many types of specialized cells, including osteoblast-like cells that contribute
      to periodontal tissue repair. The Notch signaling pathway is highly conserved and
      associated with self-renewal potential and cell-fate determination. Recently,
      several studies have focused on the relationship between Notch signaling and
      osteogenic differentiation. However, the precise mechanisms underlying this
      relationship are largely unknown. We have successfully isolated PDLSCs from both
      ovariectomized (OVX) and sham-operated rats. Both the mRNA and protein levels of
      Notch1 and Jagged1 were upregulated when PDLSCs were cultured in osteogenic
      induction media. Mineralization assays showed decreased calcium deposits in OVX
      PDLSCs treated with a gamma-secretase inhibitor compared with control cells. Thus
      Notch signaling is important in maintaining the osteogenic differentiation of
      PDLSCs in osteoporotic rats, which help in the development of a potential
      therapeutic strategy for periodontal disease in postmenopausal women. 

PMID- 24677710
TI  - Catalytic asymmetric transannulation of NH-1,2,3-triazoles with olefins.
AB  - A convenient one-pot asymmetric synthesis of 2,3-dihydropyrroles from in situ
      generated triflated triazoles and olefins is described that further expands the
      utility of azavinyl carbene chemistry and provides access to an important class
      of cyclic enamides. Mechanistic investigations support the involvement of
      triflated cyclopropylaldimine intermediates in the formation of 2,3
      dihydropyrrole. To the best of our knowledge, this is the first example of a
      chiral Bronsted acid catalyzed rearrangement of cyclopropylimines into
      enantioenriched 2,3-dihydropyrroles.

PMID- 24677711
TI  - Diabetes induces lysine acetylation of intermediary metabolism enzymes in the
      kidney.
AB  - Cells in which insulin is not required for glucose uptake are susceptible to the
      long-term complications of diabetes. Even in these tissues, however, the major
      perturbations that would otherwise be engendered by the greatly increased
      intracellular glucose concentration are mollified by adaptive changes in the
      enzymes of intermediary metabolism. These include allosteric regulation, product
      inhibition, and covalent modification as well as alterations in gene
      transcription. More recently, advances in proteomic technology have shown that
      reversible acetylation of the epsilon-amino group of lysine provides an
      additional means of modulating protein function and, in particular, enzyme
      activity. Here, we explored the extent of protein acetylation in an organ
      susceptible to the long-term complications of diabetes, examining the kidneys of
      rats with streptozotocin-induced diabetes and kidney cells exposed to high
      glucose. Using high-resolution mass spectrometry coupled with immunoaffinity
      enrichment, we identified 47 lysine-acetylated proteins in the kidneys of
      diabetic rats compared with 11 in control kidneys. Bioinformatic interrogation of
      the acetylome from diabetic animals showed a predominance of metabolic pathway
      involvement including the citrate acid cycle, glycolysis/gluconeogenesis, and
      metabolism of branched chain amino acids. Increased lysine acetylation was also
      noted in mesangial and tubular cells exposed to 25 mmol/L compared with 5.6
      mmol/L glucose. These findings highlight acetylation as a posttranslational
      modification affecting numerous proteins. Current drug discovery efforts to
      develop small molecule inhibitors and activators of various lysine acetylases and
      deacetylases offer a new potential strategy to reduce the likelihood of diabetes
      complications. 

PMID- 24677712
TI  - Incretin effect and glucagon responses to oral and intravenous glucose in
      patients with maturity-onset diabetes of the young--type 2 and type 3.
AB  - Maturity-onset diabetes of the young (MODY) is a clinically and genetically
      heterogeneous subgroup of nonautoimmune diabetes, constituting 1-2% of all
      diabetes. Because little is known about incretin function in patients with MODY,
      we studied the incretin effect and hormone responses to oral and intravenous
      glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte
      nuclear factor 1alpha (HNF1A)-diabetes (MODY3), respectively, and in matched
      healthy control subjects. Both MODY groups exhibited glucose intolerance after
      oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients
      with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon
      responses to OGTT. Both groups of patients with diabetes showed normal
      suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes,
      similar to type 2 diabetes, is characterized by an impaired incretin effect and
      inappropriate glucagon responses, whereas incretin effect and glucagon response
      to oral glucose remain unaffected in GCK-diabetes, reflecting important
      pathogenetic differences between the two MODY forms. 

PMID- 24677714
TI  - The concentration of phosphatidylethanolamine in mitochondria can modulate ATP
      production and glucose metabolism in mice.
AB  - Phosphatidylethanolamine (PE) N-methyltransferase (PEMT) catalyzes the synthesis
      of phosphatidylcholine (PC) in the liver. Mice lacking PEMT are protected against
      diet-induced obesity and insulin resistance. We investigated the role of PEMT in
      hepatic carbohydrate metabolism in chow-fed mice. A pyruvate tolerance test
      revealed that PEMT deficiency greatly attenuated gluconeogenesis. The reduction
      in glucose production was specific for pyruvate; glucose production from glycerol
      was unaffected. Mitochondrial PC levels were lower and PE levels were higher in
      livers from Pemt(-/-) compared with Pemt(+/+) mice, resulting in a 33% reduction
      of the PC-to-PE ratio. Mitochondria from Pemt(-/-) mice were also smaller and
      more elongated. Activities of cytochrome c oxidase and succinate reductase were
      increased in mitochondria of Pemt(-/-) mice. Accordingly, ATP levels in
      hepatocytes from Pemt(-/-) mice were double that in Pemt(+/+) hepatocytes. We
      observed a strong correlation between mitochondrial PC-to-PE ratio and cellular
      ATP levels in hepatoma cells that expressed various amounts of PEMT. Moreover,
      mitochondrial respiration was increased in cells lacking PEMT. In the absence of
      PEMT, changes in mitochondrial phospholipids caused a shift of pyruvate toward
      decarboxylation and energy production away from the carboxylation pathway that
      leads to glucose production. 

PMID- 24677713
TI  - Insulin inhibits cardiac contractility by inducing a Gi-biased beta2-adrenergic
      signaling in hearts.
AB  - Insulin and adrenergic stimulation are two divergent regulatory systems that may
      interact under certain pathophysiological circumstances. Here, we characterized a
      complex consisting of insulin receptor (IR) and beta2-adrenergic receptor
      (beta2AR) in the heart. The IR/beta2AR complex undergoes dynamic dissociation
      under diverse conditions such as Langendorff perfusions of hearts with insulin or
      after euglycemic-hyperinsulinemic clamps in vivo. Activation of IR with insulin
      induces protein kinase A (PKA) and G-protein receptor kinase 2 (GRK2)
      phosphorylation of the beta2AR, which promotes beta2AR coupling to the inhibitory
      G-protein, Gi. The insulin-induced phosphorylation of beta2AR is dependent on
      IRS1 and IRS2. After insulin pretreatment, the activated beta2AR-Gi signaling
      effectively attenuates cAMP/PKA activity after beta-adrenergic stimulation in
      cardiomyocytes and consequently inhibits PKA phosphorylation of phospholamban and
      contractile responses in myocytes in vitro and in Langendorff perfused hearts.
      These data indicate that increased IR signaling, as occurs in hyperinsulinemic
      states, may directly impair betaAR-regulated cardiac contractility. This beta2AR
      dependent IR and betaAR signaling cross-talk offers a molecular basis for the
      broad interaction between these signaling cascades in the heart and other tissues
      or organs that may contribute to the pathophysiology of metabolic and
      cardiovascular dysfunction in insulin-resistant states. 

PMID- 24677715
TI  - A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver
      steatosis.
AB  - MicroRNAs (miRNAs) are endogenous, noncoding, short, single-stranded RNAs that
      are evolutionarily conserved and believed to play a role in controlling a variety
      of biological processes. The roles of miRNAs in insulin resistance and liver
      steatosis, however, are largely unknown. The objective of this study was to
      evaluate the roles of miR-130a in the regulation of insulin sensitivity and liver
      steatosis. In our current study, we observed that overexpression of miR-130a-3p
      increases insulin signaling in both HepG2 cells and primary mouse hepatocytes,
      and silencing of miR-130a-3p has the opposite effects. However, miR-130a-5p has
      no effect in the regulation of insulin signaling. Consistently, whole-body and
      hepatic insulin sensitivity are improved in mice injected with adenoviruses that
      overexpress miR-130a-3p. Furthermore, we provided evidence showing that growth
      factor receptor-bound protein 10 is required for miR-130a-3p-regulated insulin
      sensitivity. On the other hand, we observed that expression of miR-130a-3p is
      decreased in the livers of db/db mice and that adenovirus-mediated overexpression
      of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of
      which is achieved via suppressing fatty acid synthase expression in these mice.
      This study identifies a novel function for hepatic miR-130a-3p in the regulation
      of insulin sensitivity and liver steatosis. 

PMID- 24677716
TI  - Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus
      lactis reverses diabetes in recent-onset NOD mice.
AB  - Growing insight into the pathogenesis of type 1 diabetes (T1D) and numerous
      studies in preclinical models highlight the potential of antigen-specific
      approaches to restore tolerance efficiently and safely. Oral administration of
      protein antigens is a preferred method for tolerance induction, but degradation
      during gastrointestinal passage can impede such protein-based therapies, reducing
      their efficacy and making them cost-ineffective. To overcome these limitations,
      we generated a tolerogenic bacterial delivery technology based on live
      Lactococcus lactis (LL) bacteria for controlled secretion of the T1D autoantigen
      GAD65370-575 and the anti-inflammatory cytokine interleukin-10 in the gut. In
      combination with short-course low-dose anti-CD3, this treatment stabilized
      insulitis, preserved functional beta-cell mass, and restored normoglycemia in
      recent-onset NOD mice, even when hyperglycemia was severe at diagnosis.
      Combination therapy did not eliminate pathogenic effector T cells, but increased
      the presence of functional CD4(+)Foxp3(+)CD25(+) regulatory T cells. These
      preclinical data indicate a great therapeutic potential of orally administered
      autoantigen-secreting LL for tolerance induction in T1D. 

PMID- 24677717
TI  - Bilirubin and progression of nephropathy in type 2 diabetes: a post hoc analysis
      of RENAAL with independent replication in IDNT.
AB  - Bilirubin, a potent endogenous antioxidant, was found to protect against the
      development of diabetic nephropathy (DN) in rodents. In humans, cross-sectional
      studies found an inverse relation between bilirubin and DN. We prospectively
      investigated whether bilirubin is associated with progression of DN toward end
      stage renal disease (ESRD). To this end, we performed a post hoc analysis in the
      Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan
      (RENAAL) trial with independent replication in the Irbesartan Diabetic
      Nephropathy Trial (IDNT). Subjects with type 2 diabetes and nephropathy with
      alanine aminotransferase, aspartate aminotransferase (AST), and bilirubin levels
      <1.5 times the upper limit of normal were included. The renal end point was
      defined as the composite of confirmed doubling of serum creatinine or ESRD.
      Bilirubin was inversely associated with the renal end point in RENAAL independent
      of age, sex, race, BMI, smoking, total cholesterol, diastolic blood pressure,
      HbA1c, treatment, estimated glomerular filtration rate, albumin-to-creatinine
      ratio, and AST. These results were confirmed in IDNT. This study indicates an
      independent inverse association of bilirubin with progression of nephropathy in
      RENAAL and IDNT. These data suggest a protective effect of bilirubin against
      progression of nephropathy in type 2 diabetes. The well-established role of
      bilirubin as an antioxidant is a potential explanation for the findings. 

PMID- 24677718
TI  - Hyaluronan and hyaluronan-binding proteins accumulate in both human type 1
      diabetic islets and lymphoid tissues and associate with inflammatory cells in
      insulitis.
AB  - Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that is present in
      pancreatic islets, but little is known about its involvement in the development
      of human type 1 diabetes (T1D). We have evaluated whether pancreatic islets and
      lymphoid tissues of T1D and nondiabetic organ donors differ in the amount and
      distribution of HA and HA-binding proteins (hyaladherins), such as inter-alpha
      inhibitor (IalphaI), versican, and tumor necrosis factor-stimulated gene-6 (TSG
      6). HA was dramatically increased both within the islet and outside the islet
      endocrine cells, juxtaposed to islet microvessels in T1D. In addition, HA was
      prominent surrounding immune cells in areas of insulitis. IalphaI and versican
      were present in HA-rich areas of islets, and both molecules accumulated in
      diabetic islets and regions exhibiting insulitis. TSG-6 was observed within the
      islet endocrine cells and in inflammatory infiltrates. These patterns were only
      observed in tissues from younger donors with disease duration of <10 years.
      Furthermore, HA and IalphaI amassed in follicular germinal centers and in T-cell
      areas in lymph nodes and spleens in T1D patients compared with control subjects.
      Our observations highlight potential roles for HA and hyaladherins in the
      pathogenesis of diabetes. 

PMID- 24677720
TI  - How do digits emerge? - mathematical models of limb development.
AB  - The mechanism that controls digit formation has long intrigued developmental and
      theoretical biologists, and many different models and mechanisms have been
      proposed. Here we review models of limb development with a specific focus on
      digit and long bone formation. Decades of experiments have revealed the basic
      signaling circuits that control limb development, and recent advances in imaging
      and molecular technologies provide us with unprecedented spatial detail and a
      broader view of the regulatory networks. Computational approaches are important
      to integrate the available information into a consistent framework that will
      allow us to achieve a deeper level of understanding, and that will help with the
      future planning and interpretation of complex experiments, paving the way to in
      silico genetics. Previous models of development had to be focused on very few,
      simple regulatory interactions. Algorithmic developments and increasing computing
      power now enable the generation and validation of increasingly realistic models
      that can be used to test old theories and uncover new mechanisms.

PMID- 24677719
TI  - Digital and analog gene circuits for biotechnology.
AB  - Biotechnology offers the promise of valuable chemical production via microbial
      processing of renewable and inexpensive substrates. Thus far, static metabolic
      engineering strategies have enabled this field to advance industrial
      applications. However, the industrial scaling of statically engineered microbes
      inevitably creates inefficiencies due to variable conditions present in large
      scale microbial cultures. Synthetic gene circuits that dynamically sense and
      regulate different molecules can resolve this issue by enabling cells to
      continuously adapt to variable conditions. These circuits also have the potential
      to enable next-generation production programs capable of autonomous transitioning
      between steps in a bioprocess. Here, we review the design and application of two
      main classes of dynamic gene circuits, digital and analog, for biotechnology.
      Within the context of these classes, we also discuss the potential benefits of
      digital-analog interconversion, memory, and multi-signal integration. Though
      synthetic gene circuits have largely been applied for cellular computation to
      date, we envision that utilizing them in biotechnology will enhance the
      efficiency and scope of biochemical production with living cells. 

PMID- 24677721
TI  - Integrin signaling in skeletal development and function.
AB  - Integrins are cell surface receptors that connect extracellular matrix (ECM)
      components to the actin cytoskeleton and transmit chemical and mechanical signals
      into the cells through adhesion complexes. Integrin-activated downstream pathways
      have been implicated in the regulation of various cellular functions, including
      proliferation, survival, migration, and differentiation. Integrin-based
      attachment to the matrix plays a central role in development, tissue
      morphogenesis, adult tissue homeostasis, remodeling and repair, and disturbance
      of the ECM-integrin-cytoskeleton signaling axis often results in diseases and
      tissue dysfunction. Increasing amount of in vitro and in vivo evidences suggest
      that integrins are pivotal for proper development, function, and regeneration of
      skeletal tissues. In this paper, we will summarize and discuss the role of
      integrins in skeletogenesis and their influence on the physiology and
      pathophysiology of cartilage, bone, and tendon.

PMID- 24677723
TI  - The chondrocytic journey in endochondral bone growth and skeletal dysplasia.
AB  - The endochondral bones of the skeleton develop from a cartilage template and grow
      via a process involving a cascade of chondrocyte differentiation steps
      culminating in formation of a growth plate and the replacement of cartilage by
      bone. This process of endochondral ossification, driven by the generation of
      chondrocytes and their subsequent proliferation, differentiation, and production
      of extracellular matrix constitute a journey, deviation from which inevitably
      disrupts bone growth and development, and is the basis of human skeletal
      dysplasias with a wide range of phenotypic severity, from perinatal lethality to
      progressively deforming. This highly coordinated journey of chondrocyte
      specification and fate determination is controlled by a myriad of intrinsic and
      extrinsic factors. SOX9 is the master transcription factor that, in concert with
      varying partners along the way, directs the different phases of the journey from
      mesenchymal condensation, chondrogenesis, differentiation, proliferation, and
      maturation. Extracellular signals, including bone morphogenetic proteins,
      wingless-related MMTV integration site (WNT), fibroblast growth factor, Indian
      hedgehog, and parathyroid hormone-related peptide, are all indispensable for
      growth plate chondrocytes to align and organize into the appropriate columnar
      architecture and controls their maturation and transition to hypertrophy.
      Chondrocyte hypertrophy, marked by dramatic volume increase in phases, is
      controlled by transcription factors SOX9, Runt-related transcription factor, and
      FOXA2. Hypertrophic chondrocytes mediate the cartilage to bone transition and
      concomitantly face a live-or-die situation, a subject of much debate. We review
      recent insights into the coordination of the phases of the chondrocyte journey,
      and highlight the need for a systems level understanding of the regulatory
      networks that will facilitate the development of therapeutic approaches for
      skeletal dysplasia.

PMID- 24677724
TI  - Chondrocyte hypertrophy in skeletal development, growth, and disease.
AB  - Most of our bones form through the process of endochondral ossification, which is
      tightly regulated by the activity of the cartilage growth plate. Chondrocyte
      maturation through the various stages of growth plate physiology ultimately
      results in hypertrophy. Chondrocyte hypertrophy is an essential contributor to
      longitudinal bone growth, but recent data suggest that these cells also play
      fundamental roles in signaling to other skeletal cells, thus coordinating
      endochondral ossification. On the other hand, ectopic hypertrophy of articular
      chondrocytes has been implicated in the pathogenesis of osteoarthritis. Thus, a
      better understanding of the processes that control chondrocyte hypertrophy in the
      growth plate as well as in articular cartilage is required for improved
      management of both skeletal growth disorders and osteoarthritis. This review
      summarizes recent findings on the regulation of hypertrophic chondrocyte
      differentiation, the cellular mechanisms involved in hypertrophy, and the role of
      chondrocyte hypertrophy in skeletal physiology and pathophysiology.

PMID- 24677722
TI  - TGFbeta signaling in cartilage development and maintenance.
AB  - Members of the transforming growth factor beta (TGFbeta) superfamily of secreted
      factors play essential roles in nearly every aspect of cartilage formation and
      maintenance. However, the mechanisms by which TGFbetas transduce their effects in
      cartilage in vivo remain poorly understood. Mutations in several TGFbeta family
      members, their receptors, extracellular modulators, and intracellular transducers
      have been described, and these usually impact the development of the
      cartilaginous skeleton. Furthermore, genome-wide association studies have linked
      components of the (TGFbeta) superfamily to susceptibility to osteoarthritis. This
      review focuses on recent discoveries from genetic studies in the mouse regarding
      the regulation of TGFbeta signaling in developing growth plate and articular
      cartilage, as well as the different modes of crosstalk between canonical and
      noncanonical TGFbeta signaling. These new insights into TGFbeta signaling in
      cartilage may open new prospects for therapies that maintain healthy articular
      cartilage.

PMID- 24677725
TI  - Coming together is a beginning: the making of an intervertebral disc.
AB  - The intervertebral disc (IVD) is a complex fibrocartilaginous structure located
      between the vertebral bodies that allows for movement and acts as a shock
      absorber in our spine for daily activities. It is composed of three components:
      the nucleus pulposus (NP), annulus fibrosus, and cartilaginous endplate. The
      characteristics of these cells are different, as they produce specific
      extracellular matrix (ECM) for tissue function and the niche in supporting the
      differentiation status of the cells in the IVD. Furthermore, cell heterogeneities
      exist in each compartment. The cells and the supporting ECM change as we age,
      leading to degenerative outcomes that often lead to pathological symptoms such as
      back pain and sciatica. There are speculations as to the potential of cell
      therapy or the use of tissue engineering as treatments. However, the nature of
      the cells present in the IVD that support tissue function is not clear. This
      review looks at the origin of cells in the making of an IVD, from the earliest
      stages of embryogenesis in the formation of the notochord, and its role as a
      signaling center, guiding the formation of spine, and in its journey to become
      the NP at the center of the IVD. While our current understanding of the molecular
      signatures of IVD cells is still limited, the field is moving fast and the
      potential is enormous as we begin to understand the progenitor and differentiated
      cells present, their molecular signatures, and signals that we could harness in
      directing the appropriate in vitro and in vivo cellular responses in our quest to
      regain or maintain a healthy IVD as we age.

PMID- 24677727
TI  - Proteases and proteomics: cutting to the core of human skin pathologies.
AB  - Preserving the integrity of the skin's outermost layer (the epidermis) is vital
      for humans to thrive in hostile surroundings. Covering the entire body, the
      epidermis forms a thin but impenetrable cellular cordon that repels external
      assaults and blocks escape of water and electrolytes from within. This structure
      exists in a perpetual state of regeneration where the production of new cellular
      subunits at the base of the epidermis is offset by the release of terminally
      differentiated corneocytes from the surface. It is becoming increasingly clear
      that proteases hold vital roles in assembling and maintaining the epidermal
      barrier. More than 30 proteases are expressed by keratinocytes or infiltrating
      immune cells and the activity of each must be maintained within narrow limits and
      confined to the correct time and place. Accordingly, over- or under-exertion of
      proteolytic activity is a common factor in a multitude of skin disorders that
      range in severity from relatively mild to life-threatening. This review explores
      the current state of knowledge on the involvement of proteases in skin diseases
      and the latest findings from proteomic and transcriptomic studies focused on
      uncovering novel (patho)physiological roles for these enzymes. 

PMID- 24677726
TI  - Tendon-to-bone attachment: from development to maturity.
AB  - The attachment between tendon and bone occurs across a complex transitional
      tissue that minimizes stress concentrations and allows for load transfer between
      muscles and skeleton. This unique tissue cannot be reconstructed following
      injury, leading to high incidence of recurrent failure and stressing the need for
      new clinical approaches. This review describes the current understanding of the
      development and function of the attachment site between tendon and bone. The
      embryonic attachment unit, namely, the tip of the tendon and the bone eminence
      into which it is inserted, was recently shown to develop modularly from a unique
      population of Sox9- and Scx-positive cells, which are distinct from tendon
      fibroblasts and chondrocytes. The fate and differentiation of these cells is
      regulated by transforming growth factor beta and bone morphogenetic protein
      signaling, respectively. Muscle loads are then necessary for the tissue to mature
      and mineralize. Mineralization of the attachment unit, which occurs postnatally
      at most sites, is largely controlled by an Indian hedgehog/parathyroid hormone
      related protein feedback loop. A number of fundamental questions regarding the
      development of this remarkable attachment system require further study. These
      relate to the signaling mechanism that facilitates the formation of an interface
      with a gradient of cellular and extracellular phenotypes, as well as to the
      interactions between tendon and bone at the point of attachment.

PMID- 24677728
TI  - Structural reevaluation of the electrophilic hypervalent iodine reagent for
      trifluoromethylthiolation supported by the crystalline sponge method for X-ray
      analysis.
AB  - Hypervalent iodine lambda3-benziodoxoles are common electrophilic transfer
      reagents known for their enhanced stability compared to their non-cyclic
      analogues. Herein we present data showing that chlorobenziodoxole reacts with two
      different thiolate nucleophiles (thiocyanate and trifluoromethylthiolate),
      resulting in the formation of stable thioperoxy complexes rather than the
      expected benziodoxole derivatives. We further report a revised structure for the
      earlier described electrophilic trifluoromethylthiolation reagent (1), which was
      previously believed to contain the benziodoxole framework. Our findings, which
      are based on a combination of analytical techniques, including the recently
      introduced crystalline sponge method for X-ray analysis, unambiguously
      demonstrate that 1 is a thioperoxy compound both in solution and the solid state.

PMID- 24677729
TI  - Methodological quality of national guidelines for pediatric inpatient conditions.
AB  - BACKGROUND: Guidelines help inform standardization of care for quality
      improvement (QI). The Pediatric Research in Inpatient Settings network published
      a prioritization list of inpatient conditions with high prevalence, cost, and
      variation in resource utilization across children's hospitals. The methodological
      quality of guidelines for priority conditions is unknown. OBJECTIVE: To rate the
      methodological quality of national guidelines for 20 priority pediatric inpatient
      conditions. DESIGN: We searched sources including PubMed for national guidelines
      published from 2002 to 2012. Guidelines specific to 1 organism, test or
      treatment, or institution were excluded. Guidelines were rated by 2 raters using
      a validated tool (Appraisal of Guidelines for Research and Evaluation) with an
      overall rating on a 7-point scale (7 = the highest). Inter-rater reliability was
      measured with a weighted kappa coefficient. RESULTS: Seventeen guidelines met
      inclusion criteria for 13 conditions; 7 conditions yielded no relevant national
      guidelines. The highest methodological-quality guidelines were for asthma,
      tonsillectomy, and bronchiolitis (mean overall rating 7, 6.5, and 6.5,
      respectively); the lowest were for sickle cell disease (2 guidelines) and dental
      caries (mean overall rating 4, 3.5, and 3, respectively). The overall weighted
      kappa was 0.83 (95% confidence interval 0.78-0.87). CONCLUSIONS: We identified a
      group of moderate to high methodological-quality national guidelines for priority
      pediatric inpatient conditions. Hospitals should consider these guidelines to
      inform QI initiatives.

PMID- 24677730
TI  - Nonylphenol regulates cyclooxygenase-2 expression via Ros-activated NF-kappaB
      pathway in sertoli TM4 cells.
AB  - The aim of this study was to investigate the signaling pathways involved in the
      cyclooxygenase (COX)-2 regulation induced by nonylphenol (NP) in mouse testis
      Sertoli TM4 cells. Our results showed that treatment of TM4 cells with NP
      increased COX-2 protein expression and interleukin-6 (IL)-6 and prostaglandin E2
      (PGE2) secretion in a dose-dependent manner. Pretreatment with reactive oxygen
      species (ROS) scavenger, N-acetylcysteine (NAC), attenuated NP-induced ROS
      production, COX-2 expression, and IL-6 and PGE2 release in TM4 cells. Exposure to
      NP stimulated activation of NF-kappaB, whereas the NF-kappaB inhibitor,
      pyrrolidine dithiocarbamate, attenuated NP-enhanced COX-2 expression and IL-6 and
      PGE2 release in TM4 cells in a dose-dependent manner. Furthermore, NAC blocked NP
      induced activation of NF-kappaB. In addition, inhibition of COX-2 mitigated NP
      induced IL-6 release. In conclusion, NP induced ROS generation, activation of NF
      kappaB pathway, COX-2 upregulation, and IL-6 and PGE2 secretion in TM4 cells. NP
      may regulate COX-2 expression via ROS-activated NF-kappaB pathway in Sertoli TM4
      cells.

PMID- 24677731
TI  - Smokers' strategic responses to sin taxes: evidence from panel data in Thailand.
AB  - In addition to quitting and cutting consumption, smokers faced with higher
      cigarette prices may compensate in several ways that mute the health impact of
      cigarette taxes. This study examines three price avoidance strategies among adult
      male smokers in Thailand: trading down to a lower-priced brand, buying individual
      sticks of cigarettes instead of packs, and substituting roll-your-own tobacco for
      factory-manufactured cigarettes. Using two panels of microlevel data from the
      International Tobacco Control Southeast Asia Study, collected in 2005 and 2006,
      we estimate the effects of a substantial excise tax increase implemented
      throughout Thailand in December 2005. We present estimates of the marginal
      effects and price elasticities for each of five consumer behaviors. We find that,
      controlling for baseline smoking characteristics, sociodemographics, and policy
      variables, quitting is highly sensitive to changes in cigarette prices, but so
      are brand choice, stick-buying, and use of roll-your-own tobacco. Neglecting such
      strategic responses leads to overestimates of a sin tax's health impact, and
      neglecting product substitution distorts estimates of the price elasticity of
      cigarette demand. We discuss the implications for consumer welfare and several
      policies that mitigate the adverse impact of consumer responses.

PMID- 24677732
TI  - Impact of the accuracy of automatic segmentation of cell nuclei clusters on
      classification of thyroid follicular lesions.
AB  - Automatic segmentation of cell nuclei clusters is a key building block in systems
      for quantitative analysis of microscopy cell images. For that reason, it has
      received a great attention over the last decade, and diverse automatic approaches
      to segment clustered nuclei with varying levels of performance under different
      test conditions have been proposed in literature. To the best of our knowledge,
      however, so far there is no comparative study on the methods. This study is a
      first attempt to fill this research gap. More precisely, the purpose of this
      study is to present an objective performance comparison of existing state-of-the
      art segmentation methods. Particularly, the impact of their accuracy on
      classification of thyroid follicular lesions is also investigated
      "quantitatively" under the same experimental condition, to evaluate the
      applicability of the methods. Thirteen different segmentation approaches are
      compared in terms of not only errors in nuclei segmentation and delineation, but
      also their impact on the performance of system to classify thyroid follicular
      lesions using different metrics (e.g., diagnostic accuracy, sensitivity,
      specificity, etc.). Extensive experiments have been conducted on a total of 204
      digitized thyroid biopsy specimens. Our study demonstrates that significant
      diagnostic errors can be avoided using more advanced segmentation approaches. We
      believe that this comprehensive comparative study serves as a reference point and
      guide for developers and practitioners in choosing an appropriate automatic
      segmentation technique adopted for building automated systems for specifically
      classifying follicular thyroid lesions.

PMID- 24677733
TI  - Bidirectional regulation of mRNA translation in mammalian cells by using PUF
      domains.
AB  - The regulation of gene expression is crucial in diverse areas of biological
      science, engineering, and medicine. A genetically encoded system based on the RNA
      binding domain of the Pumilio and FBF (PUF) proteins was developed for the
      bidirectional regulation (i.e., either upregulation or downregulation) of the
      translation of a target mRNA. PUF domains serve as designable scaffolds for the
      recognition of specific RNA elements and the specificity can be easily altered to
      target any 8-nucleotide RNA sequence. The expression of a reporter could be
      varied by over 17-fold when using PUF-based activators and repressors. The
      specificity of the method was established by using wild-type and mutant PUF
      domains. Furthermore, this method could be used to activate the translation of
      target mRNA downstream of PUF binding sites in a light-dependent manner. Such
      specific bidirectional control of mRNA translation could be particularly useful
      in the fields of synthetic biology, developmental biology, and metabolic
      engineering. 

PMID- 24677734
TI  - Minimizing femoral artery access complications during percutaneous coronary
      intervention: a comprehensive review.
AB  - Major bleeding complications after percutaneous coronary intervention (PCI)
      increase patient morbidity, prolong the hospital stay and costs, and are
      associated with reduced survival. Transfemoral access is still preferred at many
      centers given its familiarity and ease of use and is necessary in cases where
      large bore access is needed. Multimodality imaging with fluoroscopy,
      ultrasonography, and angiography can facilitate proper puncture of the common
      femoral artery. A proper technique (which includes femoral artery puncture and
      vascular access site closure) associated with adequate pharmacotherapy (both
      during PCI and peri-procedural, for the treatment of the underlying coronary
      artery disease) has been shown to reduce the risk of bleeding and vascular
      complications associated with femoral artery access. Avoiding the use of arterial
      sheaths >6 French may further reduce the risk of bleeding. Data with vascular
      closure devices as a bleeding avoidance strategy are evolving but when used
      appropriately may further reduce the risk of bleeding and vascular access
      complications, and in this regard are synergistic with bivalirudin. Randomized
      trials to confirm these recommendations are needed.

PMID- 24677735
TI  - Unravelling offending in schizophrenia: factors characterising subgroups of
      offenders.
AB  - BACKGROUND: Previous studies have led to suggestions that there are at least
      three sub-types of offenders with schizophrenia, but these have not previously
      been examined simultaneously in one sample. AIMS: The aims of this study were to
      investigate categorisation of offenders with psychosis as early or late starters
      or late first offenders, and test the hypotheses that, compared with non
      offenders with psychosis, early starters would be characterised by low
      educational or occupational achievement, negative childhood experiences and early
      substance use, whereas positive psychotic symptoms would characterise late
      starters or late first offenders. METHODS: A retrospective file study was
      conducted, yielding 97 early starters, 100 late starters and 26 late first
      offenders identified from a specialist inpatient forensic mental health
      assessment service and 129 non-offenders identified from general psychiatric
      services in the same geographic region, all with schizophreniform psychoses.
      RESULTS: We found little difference between early and later starters in terms of
      measured antecedents, but substance misuse was up to 20 times less likely among
      late first offenders. Persecutory and/or grandiose delusions were more strongly
      associated with each offender group compared with non-offenders, most so with
      late first offenders. CONCLUSIONS: Our findings underscore the importance of
      treating delusions--for safety as well as health. Childhood antecedents may be
      less important indicators of offender sub-types among people with psychosis than
      previously thought. When patients present with grandiose or persecutory delusions
      over the age of 35 years without co-morbid substance misuse disorders, but with a
      history of childhood neglect and low educational achievement, particular care
      should be taken to assess risk of violence.

PMID- 24677736
TI  - Functional variability of glutathione S-transferases in Basque populations.
AB  - OBJECTIVES: Glutathione S-transferases (GSTs) are enzymes involved in Phase II
      reactions. They play a key role in cellular detoxification. Various studies have
      shown that genes coding for the GST are highly polymorphic and some of these
      variants are directly associated with a decrease of enzyme activity making
      individuals more susceptible to different clinical phenotypes. The aim of this
      study is to investigate the genetic variability of GST genes among human
      populations. We have focused our attention on the polymorphic variants of the
      GSTA1, GSTM1, GSTO1, GSTO2, GSTP1, GSTT1, and GSTT2B genes. METHODS: These
      polymorphisms were analyzed in a whole sample of 151 individuals: 112
      autochthonous Navarrese Basques, and 39 non-autochthonous Navarrese Basques. DNA
      extraction from plasma was performed by using the phenol:chloroform:isoamylic
      alcohol method. Genotyping of the gene polymorphisms was performed by PCR
      Multiplex and the PCR-RFLP method. We applied correspondence analysis and built
      frequency-maps to compare the genetic structure in worldwide populations.
      RESULTS: Our results were compared with data available on the Human Genome
      Diversity Project (HGDP) and on the 1,000 Genomes Project to obtain information
      on the functional variability of GSTs in Basques. Our data indicated that Basque
      communities showed a higher differentiation of certain functional GST variants
      (i.e., GSTM1-positive/null genotype, GSTP1*I105V, and GSTT2B*1/0) than other
      European and Mediterranean populations. CONCLUSIONS: This might account for
      epidemiological differences in the predisposition to diseases and drug response
      among Basques and could be used to design and interpret genetic association
      studies for this particular population.

PMID- 24677737
TI  - Sensitive and rapid determination of elemental nanosulfur/sulfur by liquid
      chromatography.
AB  - In order to identify the most suitable method for the estimation of nanosulfur
      for studying its residue dynamics, the present work was taken up. HPLC and GC
      methods were explored for its analysis. A comparative study of the existing
      analytical methods for the quality control of nanosulfur was undertaken. UV
      spectrophotometry and HPLC methods were superior with lower LOD when compared to
      GC-MS, which was not satisfactory due to breakage of catenated S20 into S6 and S8
      . The method has been validated by analyzing various nanosulfur formulations of
      known concentrations. The recovery of the UV and HPLC methods ranged from 80.71
      to 109.51% and 82.31 to 109.84%, respectively. The LOD of UV, GC-MS, and HPLC is
      4, 20, and 1 ppm, respectively. The retention time of sulfur was 13.77 (HPLC),
      2.89 (ultra high performance liquid chromatography), and 12.715 + 21.524 min (GC
      MS). The method was successfully utilized for estimating sulfur in natural
      samples such as water from a sulfur hot spring and wastewater. The method has
      been validated by following the method recommended by the American Society for
      Testing and Materials. The HPLC method emerged as the best analytical method for
      the estimation of elemental sulfur.

PMID- 24677738
TI  - Comments on ethylenediaminetetraacetic acid contained in trypsin detaching cells
      for apoptosis detection.

PMID- 24677739
TI  - Cartilage regeneration using biodegradable oxidized alginate/hyaluronate
      hydrogels.
AB  - Despite the widespread use of alginate (AL) hydrogels in many biomedical
      applications, including tissue engineering, AL is inherently non-degradable under
      physiological conditions. We hypothesized that degradable alginate (dAL) would be
      useful for cartilage regeneration when combined with hyaluronate (HA). We
      prepared dAL by partial oxidation of AL using sodium periodate, and the
      degradation rate of AL hydrogel was able to be regulated by control of sodium
      periodate concentration. The degradable oxidized AL/HA gels were formed in the
      presence of cells and their characteristics were investigated. dAL/HA gels with
      primary chondrocytes were injected subcutaneously into mice. Effective cartilage
      regeneration was observed after 6 weeks of transplantation based on histological
      analysis. Moreover, substantial secretion of sulfated glycosaminoglycans and
      expression of chondrogenic marker genes were also observed compared with non
      dAL/HA gels. These results indicate that dAL/HA hydrogels may be useful in
      cartilage regeneration, and in many tissue engineering applications.

PMID- 24677741
TI  - Simplified silvestrol analogues with potent cytotoxic activity.
AB  - The complex natural products silvestrol (1) and episilvestrol (2) are inhibitors
      of translation initiation through binding to the DEAD-box helicase eukaryotic
      initiation factor 4A (eIF4A). Both compounds are potently cytotoxic to cancer
      cells in vitro, and 1 has demonstrated efficacy in vivo in several xenograft
      cancer models. Here we show that 2 has limited plasma membrane permeability and
      is metabolized in liver microsomes in a manner consistent with that reported for
      1. In addition, we have prepared a series of analogues of these compounds where
      the complex pseudo-sugar at C6 has been replaced with chemically simpler moieties
      to improve drug-likeness. Selected compounds from this work possess excellent
      activity in biochemical and cellular translation assays with potent activity
      against leukemia cell lines. 

PMID- 24677740
TI  - Prevalence and outcome of non-alcoholic fatty liver disease in adolescents and
      young adults undergoing weight loss surgery.
AB  - BACKGROUND/OBJECTIVE: We evaluated the prevalence of non-alcoholic fatty liver
      disease (NAFLD) and non-alcoholic steatohepatitis (NASH) in 27 adolescents
      referred for weight loss surgery (WLS). RESULTS: On biopsy, 18 patients (66.7%)
      had NAFLD, and of those, 10 (37.0%) had NASH and 11 (40.7%) had fibrosis.
      Insulin, HbA1C and homeostatic model assessment of insulin resistance (HOMA-IR)
      were significantly higher in patients with NASH than those without NASH.
      Following WLS, 40% of patients with NASH had persistently elevated
      aminotransferase levels despite weight loss. CONCLUSION: We found that NASH is
      underdiagnosed in adolescents referred for WLS, and that hyperinsulinaemia, HOMA
      IR and HbA1c can aid in identifying high-risk patients.

PMID- 24677742
TI  - Optical imaging of liquid crystals at the nanoscale.
AB  - The instrumentation associated with near-field scanning optical microscopy (NSOM)
      can be exploited to provide three-dimensional structure and dynamic information
      about liquid crystals at scales not possible with diffraction-limited tools. This
      Minireview focuses on our use of NSOM techniques to probe spatial variations of
      the nematic director and the nematic orientational order parameter on length
      scales as small as a few nanometers. 

PMID- 24677743
TI  - Antibody-drug conjugates: an emerging concept in cancer therapy.
AB  - Traditional cancer chemotherapy is often accompanied by systemic toxicity to the
      patient. Monoclonal antibodies against antigens on cancer cells offer an
      alternative tumor-selective treatment approach. However, most monoclonal
      antibodies are not sufficiently potent to be therapeutically active on their own.
      Antibody-drug conjugates (ADCs) use antibodies to deliver a potent cytotoxic
      compound selectively to tumor cells, thus improving the therapeutic index of
      chemotherapeutic agents. The recent approval of two ADCs, brentuximab vedotin and
      ado-trastuzumab emtansine, for cancer treatment has spurred tremendous research
      interest in this field. This Review touches upon the early efforts in the field,
      and describes how the lessons learned from the first-generation ADCs have led to
      improvements in every aspect of this technology, i.e., the antibody, the
      cytotoxic compound, and the linker connecting them, leading to the current
      successes. The design of ADCs currently in clinical development, and results from
      mechanistic studies and preclinical and clinical evaluation are discussed.
      Emerging technologies that seek to further advance this exciting area of research
      are also discussed. 

PMID- 24677744
TI  - Advances in metabolic engineering of yeast Saccharomyces cerevisiae for
      production of chemicals.
AB  - Yeast Saccharomyces cerevisiae is an important industrial host for production of
      enzymes, pharmaceutical and nutraceutical ingredients and recently also commodity
      chemicals and biofuels. Here, we review the advances in modeling and synthetic
      biology tools and how these tools can speed up the development of yeast cell
      factories. We also present an overview of metabolic engineering strategies for
      developing yeast strains for production of polymer monomers: lactic, succinic,
      and cis,cis-muconic acids. S. cerevisiae has already firmly established itself as
      a cell factory in industrial biotechnology and the advances in yeast strain
      engineering will stimulate development of novel yeast-based processes for
      chemicals production. 

PMID- 24677745
TI  - Clinical manifestations of 17 patients affected with mucopolysaccharidosis type
      VI and eight novel ARSB mutations.
AB  - Mucopolysaccharidosis (MPS) type VI or Maroteaux-Lamy syndrome is a very rare
      autosomal recessive lysosomal storage disease, caused by a deficiency of the
      enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB). Clinical
      examination, biochemical studies, and molecular genetic analyses have been
      performed in 17 patients affected with MPS VI from 15 unrelated families from
      Thailand, India, and Turkey. Large ear lobule appears to be a newly recognized
      finding of this syndrome. Mutation analysis of the ARSB gene revealed seven
      missense and three frameshift mutations of which eight were novel. Novel missense
      mutations were p.Asp53Asn, p.Val376Glu, p.Glu390Lys, p.Pro445Leu, and
      p.Trp450Cys, while an Indian patient was homozygous for two novel missense
      mutations (p.Pro445Leu and p.Trp450Cys). Three novel frameshift mutations were
      p.Pro70fsX123, p.Ser403fs, and p.Thr526fs. Two previously reported mutations,
      p.Arg160Gln and p.Leu321Pro, were also observed in our cohort. The amino acid
      Arg160 appears to be the mutational hot spot for the ARSB gene. Five patients
      homozygous for p.Leu321Pro mutation had early onset of the disease, and haplotype
      analysis showed that the mutation is a founder mutation in Turkish population.

PMID- 24677746
TI  - HIF-1alpha and CA-IX as predictors of locoregional control for determining the
      optimal treatment modality for early-stage laryngeal carcinoma.
AB  - BACKGROUND: The purpose of this study was to examine the predictive value of
      hypoxia-inducible factor (HIF)-1alpha, carbonic anhydrase (CA)-IX, glucose
      transporter (GLUT)-1, cyclooxygenase (COX)-2, Ki-67, and erythropoietin receptor
      (EPOR) as immunohistochemical markers for determining the optimal treatment
      modality for early stage laryngeal carcinoma. METHODS: Tissue samples from 42
      early stage laryngeal carcinomas treated with radiotherapy alone were analyzed
      immunohistochemically for the expression of 6 markers. The Kaplan-Meier method,
      univariate and multivariate analyses, and the Cox proportional hazards model were
      used to analyze the associations between patient and tumor characteristics and
      immunohistochemical results, and locoregional control. RESULTS: Increased
      expression of HIF-1alpha and CA-IX was significantly correlated with residual
      tumor; no correlations were observed for the other immunohistochemical markers.
      CONCLUSION: High levels of HIF-1alpha or CA-IX expression were significantly
      correlated with residual tumor after radiotherapy for early stage laryngeal
      carcinomas. Alternative treatment modalities to primary radiotherapy should be
      considered for early stage laryngeal carcinomas showing high HIF-1alpha or CA-IX
      expression.

PMID- 24677747
TI  - Bile analysis using high-throughput FTIR spectroscopy for the diagnosis of
      malignant biliary strictures: a pilot study in 57 patients.
AB  - This study aimed at determining whether FTIR spectroscopy is able to distinguish
      bile samples from patients with and without malignant biliary strictures. Bile
      samples were collected in 19 patients with malignant biliary strictures and 38
      with benign biliary diseases during endoscopic procedures. FTIR spectra were
      acquired on dried drops of whole bile, aqueous and organic phases obtained after
      lipid extraction. Data were analyzed by principal component analysis and by the
      support vector machine classification using a leave-n-out cross validation
      procedure. This was applied to the whole set of spectra and the mean and median
      spectra of each patient. By leaving one patient out, the classifier allowed
      discriminating patients with and without malignant biliary strictures with a
      sensitivity between 82% and 95% and a specificity between 85% and 100%. Using a
      randomized leave-n -out cross-validation with n = 2, 5 and 10 patients, the
      sensitivity decreased slightly by about 5 to 10% while the specificity remained
      stable, suggesting the robustness of the classifier. FTIR spectroscopy combined
      with chemometrics therefore shows potential to differentiate bile from patients
      with and without malignant biliary strictures. Although promising, the results of
      this pilot study cannot be generalized and needs to be confirmed in a larger
      population.

PMID- 24677748
TI  - Ozonated graphene oxide film as a proton-exchange membrane.
AB  - Graphene oxide (GO) contains several chemical functional groups that are attached
      to the graphite basal plane and can be manipulated to tailor GO for specific
      applications. It is now revealed that the reaction of GO with ozone results in a
      high level of oxidation, which leads to significantly improved ionic (protonic)
      conductivity of the GO. Freestanding ozonated GO films were synthesized and used
      as efficient polymer electrolyte fuel cell membranes. The increase in protonic
      conductivity of the ozonated GO originates from enhanced proton hopping, which is
      due to the higher content of oxygenated functional groups in the basal planes and
      edges of ozonated GO as well as the morphology changes in GO that are caused by
      ozonation. The results of this study demonstrate that the modification of
      dispersed GO presents a powerful opportunity for optimizing a nanoscale material
      for proton-exchange membranes.

PMID- 24677749
TI  - BRAF V600E mutational status in pediatric thyroid cancer.
AB  - BACKGROUND: Clinical outcome of papillary thyroid carcinoma (PTC) in children
      differs significantly from that of adults. There is no clear explanation of this
      difference although previous studies have demonstrated a lower prevalence of the
      BRAF(V600E) mutation in PTC of children. However, data are limited due to the
      rarity of this diagnosis. BRAF(V600E) mutation prevalence and its relationship
      with outcome in pediatric PTC remain unclear. PROCEDURE: BRAF(V600E) mutational
      status was determined in 27 PTC patients less than 22 years of age using
      restriction fragment length polymorphism (RFLP) analysis. The relationship
      between BRAF(V600E) mutation status, patient and tumor characteristics as well as
      progression-free survival (PFS) were analyzed. RESULTS: BRAF(V600E) was present
      in 63% of patients and occurred more often in male patients versus females (P =
      0.033). Presence of the mutation did not correlate with any difference in extent
      of disease at diagnosis, tumor size, capsular invasion, vascular invasion, soft
      tissue invasion, or margin status. At 10 years, PFS for BRAF(V600E) positive
      versus negative patients was 55.5% versus 70.0%, respectively (P = 0.48). Overall
      survival was 100% and median follow-up was 13.9 years. CONCLUSIONS: This study of
      pediatric PTC demonstrates that BRAF(V600E) mutations occur in children at a rate
      comparable to adults. We found a correlation of BRAF(V600E) with the male gender,
      but no evidence that the mutation correlates with more extensive or aggressive
      disease. This analysis suggests that differences in disease course of PTC in
      children versus adults are not strongly dependent upon the presence of the
      BRAF(V600E) mutation.

PMID- 24677750
TI  - Alphavbeta6 is required in maintaining the intestinal epithelial barrier
      function.
AB  - Epithelial barrier dysfunction is involved in a large number of diseases, but the
      pathogenesis is unclear. Integrin alphavbeta6 (avb6) in involved in the
      maintenance of the mucosal homeostasis. We have investigated the role of avb6 in
      maintaining the epithelial barrier function. Using T84 monolayers cultures,
      transepithelial electric resistance (TER) and permeability to ovalbumin (OVA)
      were measured as indicators of functioning. The antigenicity of OVA collected
      from the Transwell basal chambers was assessed using OVA-specific T cell
      proliferation. Knockdown of the avb6 genes increased the permeability of T84
      monolayers to OVA, but did not affect TER. The deficiency of avb6-related
      hyperpermeability in T84 monolayers could be compensated by adding exogenous avb6
      to the culture. The OVA samples collected from the basal chambers had strong
      antigenicity as it markedly induced the antigen specific T cell proliferation.
      Addition of recombinant avb6 blocked increases in permeability of T84 monolayers
      to OVA induced by tumor necrosis factor-alpha. 

PMID- 24677752
TI  - Study of the retention behavior of iodinated X-ray contrast agents in hydrophilic
      interaction liquid chromatography, comparing bare silica and zwitterionic
      stationary phases.
AB  - Iodinated X-ray contrast media are the most widely used pharmaceuticals for
      intravascular administration in X-ray diagnostic procedures. The increasing
      concern of the fate of these compounds into the environment has led to the
      development of analytical methods to determine them. However, these methods
      present problems due to the polar character of these analytes. In this paper,
      hydrophilic interaction LC is presented as an alternative technique. The
      retention of iodinated X-ray contrast media was studied in two bare silica phases
      with different particle designs (i.e. porous and Fused CoreTM) and a zwitterionic
      sulfoalkylbetaine phase. The effect of the most important parameters of the
      mobile phase was studied for each stationary phase. It was observed that optimal
      mobile phase conditions included buffers with a high buffering capacity.
      Additionally, the retention mechanisms involved were studied in order to provide
      some insight into the possible occurring interactions. The contributions of
      partition and adsorption and the effect of the temperature on the retention of
      analytes were evaluated on all of the stationary phases. 

PMID- 24677751
TI  - Pax3 and Tbx5 specify whether PDGFRalpha+ cells assume skeletal or cardiac muscle
      fate in differentiating embryonic stem cells.
AB  - Embryonic stem cells (ESCs) represent an ideal model to study how lineage
      decisions are established during embryonic development. Using a doxycycline
      inducible mouse ESC line, we have previously shown that expression of the
      transcriptional activator Pax3 in early mesodermal cells leads to the robust
      generation of paraxial mesoderm progenitors that ultimately differentiate into
      skeletal muscle precursors. Here, we show that the ability of this transcription
      factor to induce the skeletal myogenic cell fate occurs at the expenses of the
      cardiac lineage. Our results show that the PDGFRalpha+FLK1--subfraction
      represents the main population affected by Pax3, through downregulation of
      several transcripts encoding for proteins involved in cardiac development. We
      demonstrate that although Nkx2-5, Tbx5, and Gata4 negatively affect Pax3 skeletal
      myogenic activity, the cardiac potential of embryoid body-derived cultures is
      restored solely by forced expression of Tbx5. Taking advantage of this model, we
      used an unbiased genome-wide approach to identify genes whose expression is
      rescued by Tbx5, and which could represent important regulators of cardiac
      development. These findings elucidate mechanisms regulating the commitment of
      mesodermal cells in the early embryo and identify the Tbx5 cardiac transcriptome.

PMID- 24677753
TI  - Clinical value of chest computerized tomography scans in patients admitted with
      pneumonia.
AB  - Patients admitted with pneumonia often receive a chest computed tomography (CT)
      scan for a variety of reasons. We conducted this study to evaluate our overall
      utilization and the clinical impact of CT scans in patients admitted to our
      institution with pneumonia. Patients admitted to our facility from January 2008
      through November 2011 with a confirmed diagnosis of pneumonia were eligible for
      evaluation. Information related to patient demographics, performance of a CT
      scan, pneumonia-related procedures, severity of illness, and outcomes was
      collected. One hundred ninety-five patients met inclusion criteria. Sixty-nine
      patients had CT scans performed. CT scans were performed more often in younger
      patients (58.1 +/- 19.0 vs 66.8 +/- 18.6, P = 0.002), individuals with lower CURB
      65 (Confusion, Urea, Respiratory rate, Blood pressure, Age > 65) scores (1.7 +/-
      1.4 vs 2.2 +/- 1.4, P = 0.037), and those with no infiltrates or consolidation on
      plain radiographs (26.9% vs 7.1%, P < 0.0001). Patients who had a procedure
      performed had longer average length of stays (15.3 +/- 11.9 vs 6.8 +/- 4.1 days,
      P = 0.016). Pneumonia-related procedures were more likely performed in patients
      who had a CT scan. Specific guidelines and objective rules need to be developed
      to prospectively guide the use of advanced imaging techniques in pneumonia
      patients.

PMID- 24677754
TI  - Use of histopathology and elemental accumulation in different organs of two
      benthophagous fish species as indicators of river pollution.
AB  - The bottom feeding fish species have a good potential to be used for assessments
      of pollution, as they are under pressure from pollutants from both water and
      sediments. In this study, the level of similarity of histopathological responses
      to pollution in gills and liver between barbel (Barbus barbus) and sterlet
      (Acipenser ruthenus) from the Danube River was assessed, and compared with
      elemental concentrations in their gills, liver, and muscle. Results indicate that
      the detected metal concentrations were likely cause of different tissue responses
      in gills and liver of the two investigated fish species. Statistical analysis
      indicated a clear differentiation of the two species based on elemental
      concentrations and the level of histopathological changes in gills and liver.
      Metal concentrations exceeded maximum acceptable concentrations in a number of
      analyzed specimens, which indicates the importance of this type of monitoring.
      Results indicate that barbel is a better indicator for specific, rather narrow
      sites, whereas sterlet is a better indicator of larger (longer) water current
      segments. Obtained information could be of importance for both scientists and
      fishery and water management authorities working on the development of water
      monitoring programs.

PMID- 24677755
TI  - Update on canine MSC markers.

PMID- 24677756
TI  - Do public smoking bans have an impact on active smoking? Evidence from the UK.
AB  - The literature on the effects of public smoking bans on smoking behaviour
      presents conflicting results and there is limited evidence on their impact on
      active smoking. This paper evaluates the impact of smoking bans on active smoking
      using data from the British Household Panel Survey and exploiting the policy
      experiment provided by the differential timing of the introduction of the bans in
      Scotland and England. We assess the short-term impact of the smoking bans by
      employing a series of flexible difference-in-differences fixed effects panel data
      models. We find that the introduction of the public smoking bans in England and
      Scotland had limited short-run effects on both smoking prevalence and the total
      level of smoking. Although we identify significant differences in trends in
      smoking consumption across the survey period by population sub-groups, we find
      insufficient evidence to conclude that these were affected by the introduction of
      the smoking bans. These results challenge those found in the public health
      literature but are in line with the most recent strand of economic literature
      indicating that there is no firm evidence on the effects of smoking bans on
      smoking.

PMID- 24677757
TI  - Laryngeal replacement with an artificial larynx after total laryngectomy: the
      possibility of restoring larynx functionality in the future.
AB  - BACKGROUND: Most patients perceive total laryngectomy as a mutilation carrying
      with it a loss of physical and psychological integrity. Thus, an artificial
      larynx system that can replace the laryngeal functions would significantly
      improve the quality of life for the afflicted patients. METHODS: This report,
      with accompanying video, presents the first case in an ongoing clinical trial of
      laryngeal rehabilitation using an artificial larynx after total laryngectomy for
      squamous cell carcinoma, for an 8-month follow-up period. We depict the
      prosthesis' features, our 2-step surgical procedure, and the outcome. The
      prosthesis is formed of 2 parts: (1) a tracheal prosthesis with a porous titanium
      junction with trachea, which was implanted in the first step to ensure its
      colonization, and (2) a removable part composed of concentric valves that enable
      inhalation and exhalation. The second part was implanted endoscopically. The
      implant was monitored with a retrograde nasofibroscopy of the tracheal prosthesis
      lumen and CT scans over a course of 8 months. RESULTS: The patient's functioning
      in the relevant postoperative problem areas, such as swallowing, breathing, and
      smelling, has significantly improved. The patient was able to talk in a
      whispering fashion while the tracheostomy was temporarily closed. The implant's
      porous part was in the process of being colonized by the surrounding tissue and
      no fistulas were observed as evidenced by barium swallow. CONCLUSION: As the
      current case shows, tracheotomy closure can be performed, and laryngeal functions
      are restored, by means of an implant. With further improvements, this system can
      alleviate the need for a permanent tracheostomy after total laryngectomy, while
      maintaining important larynx functions intact.

PMID- 24677759
TI  - Cryogenic colocalization microscopy for nanometer-distance measurements.
AB  - The main limiting factor in spatial resolution of localization microscopy is the
      number of detected photons. Recently we showed that cryogenic measurements
      improve the photostability of fluorophores, giving access to Angstrom precision
      in localization of single molecules. Here, we extend this method to colocalize
      two fluorophores attached to well-defined positions of a double-stranded DNA. By
      measuring the separations of the fluorophore pairs prepared at different design
      positions, we verify the feasibility of cryogenic distance measurement with sub
      nanometer accuracy. We discuss the important challenges of our method as well as
      its potential for further improvement and various applications.

PMID- 24677761
TI  - Anti-proliferative activity of nano-formulated phenolato titanium(IV) complexes
      against cancer cells.
AB  - Nanoparticles of titanium(IV) complexes of phenolato ligands were formed and
      evaluated for cytotoxicity toward human HT-29 colon cancer, murine T-25 lymphoma,
      and murine HU-2 multidrug-resistant (MDR) cells. The nano-formulation, besides
      increasing the complexes' shelf lives, is particularly efficient in overcoming
      limitations in solubility and cell-penetration, thus enhancing biological
      accessibility; large complexes that were inactive when measured in a non
      formulated form showed marked activity when nano-formulated. For active and
      accessible small complexes, the effect of the formulation was negligible. Most
      complexes showed similar activity toward MDR cells and their drug-sensitive
      analogues, further increasing their therapeutic potential. An exception is a
      particularly hydrophobic complex, which is presumably more accessible to
      interaction with the membrane ABCB1 (MDR1) transporter active in the multidrug
      resistance of HU-2 cells. The most efficient compound is a mononuclear complex of
      a single hexadentate ligand, combining particularly high activity and hydrolytic
      stability with accessibility aided by the nano-formulation. 

PMID- 24677760
TI  - Breathprints of childhood obesity: changes in volatile organic compounds in obese
      children compared with lean controls.
AB  - OBJECTIVE: The objective of this study was to investigate changes in volatile
      organic compounds (VOCs) in exhaled breath in overweight/obese children compared
      with their lean counterparts. STUDY DESIGN: Single exhaled breath was collected
      and analyzed per protocol using selective ion flow tube mass spectrometry (SIFT
      MS). RESULTS: Sixty overweight/obese children and 55 lean controls were included.
      Compared with the lean group, the obese group was significantly older (14.1 +/-
      2.8 vs. 12.1 +/- 3.0 years), taller (164.8 +/- 10.9 vs. 153.3 +/- 17.1 cm) and
      more likely to be Caucasian (60% vs. 35.2%); P < 0.05 for all. A comparison of
      the SIFT-MS results of the obese group with the lean group revealed differences
      in concentration of more than 50 compounds. A panel of four VOCs can identify the
      presence of overweight/obesity with excellent accuracy. Further analysis revealed
      that breath isoprene, 1-decene, 1-octene, ammonia and hydrogen sulfide were
      significantly higher in the obese group compared with the lean group (P value <
      0.01 for all). CONCLUSION: Obese children have a unique pattern of exhaled VOCs.
      Changes in VOCs observed in this study may help to gain insight into
      pathophysiological processes and pathways leading to the development of childhood
      obesity.

PMID- 24677762
TI  - FKBP14-related Ehlers-Danlos syndrome: expansion of the phenotype to include
      vascular complications.
AB  - Biallelic mutations in FKBP14 cause a recessive form of Ehlers-Danlos syndrome
      (EDS) characterized by progressive kyphoscoliosis, myopathy, and hearing loss. To
      date, four children and one adult with this condition have been reported. We
      recently identified a 42-year-old man with severe kyphoscoliosis,
      restrictive/obstructive lung disease, short stature, mild hearing loss, decreased
      muscle mass, and a dissection of the celiac artery at age 41. He also had
      complete occlusion of the superior mesenteric artery with compensatory flow
      through an enlarged and tortuous inferior mesenteric artery. He was homozygous
      for a previously identified FKBP14 mutation, c.362dupC, p.(Glu122Argfs*7). He had
      no mutations in COL3A1, ACTA2, TGFBR1, TGFBR2, or SMAD3. The FKBP14 mutations in
      our patient occurred on the same haplotype as others with this same mutation.
      Although one family member in a previous report was thought to have early
      vascular complications, it could not be confirmed that she had biallelic
      mutations in FKBP14. This report expands the phenotype of FKBP14-related EDS to
      include risk for vascular complications and also raises the question of whether
      the shared haplotype represents a risk allele or founder mutation.

PMID- 24677763
TI  - 1-(1H-indol-3-yl)ethanamine derivatives as potent Staphylococcus aureus NorA
      efflux pump inhibitors.
AB  - The synthesis of 37 1-(1H-indol-3-yl)ethanamine derivatives, including 12 new
      compounds, was achieved through a series of simple and efficient chemical
      modifications. These indole derivatives displayed modest or no intrinsic anti
      staphylococcal activity. By contrast, several of the compounds restored, in a
      concentration-dependent manner, the antibacterial activity of ciprofloxacin
      against Staphylococcus aureus strains that were resistant to fluoroquinolones due
      to overexpression of the NorA efflux pump. Structure-activity relationships
      studies revealed that the indolic aldonitrones halogenated at position 5 of the
      indole core were the most efficient inhibitors of the S. aureus NorA efflux pump.
      Among the compounds, (Z)-N-benzylidene-2-(tert-butoxycarbonylamino)-1-(5-iodo-1H
      indol-3-yl)ethanamine oxide led to a fourfold decrease of the ciprofloxacin
      minimum inhibitory concentration against the SA-1199B strain when used at a
      concentration of 0.5 mg L(-1) . To the best of our knowledge, this activity is
      the highest reported to date for an indolic NorA inhibitor. In addition, a new
      antibacterial compound, tert-butyl (2-(3-hydroxyureido)-2-(1H-indol-3
      yl)ethyl)carbamate, which is not toxic for human cells, was also found. 

PMID- 24677764
TI  - Salvage of side branch by provisional "TAP technique" using AbsorbTM
      bioresorbable vascular scaffolds for bifurcation lesions: first case reports with
      technical considerations.
AB  - Recent technological developments have led to the development of AbsorbTM
      bioresorbable vascular scaffold (BVS) [Abbott Vascular, Santa Clara, USA] for
      percutaneous treatment of coronary artery disease by percutaneous coronary
      intervention (PCI). The BVS is now approved for use in many countries but
      experience in bifurcation lesions is limited and largely unreported and concerns
      still exist about its use across major side branches. We report for the first
      time, the successful use of the "T and Protrusion" (TAP) technique of deploying
      BVS into the side branch (SB) through the struts of main branch (MB) BVS to
      salvage a suboptimal result and threatened closure of a SB in three cases when
      treating bifurcation lesions with a planned single BVS strategy. The TAP
      technique was successful in all cases and there were no complications. All
      patients continue to do well at short-term follow-up. This case report provides
      information regarding the feasibility as well as technical and procedural
      insights when using BVS for bifurcation lesions.

PMID- 24677765
TI  - Synthesis and activity of isoxazoline vinyl ester  pseudopeptides as proteasome
      inhibitors.
AB  - The ubiquitin-proteasome pathway (UPP) influences essential cellular functions
      including cell growth, differentiation, apoptosis, signal transduction, antigen
      processing and inflammatory responses. The main proteolytic component of the UPP
      is the 26S proteasome, which is responsible for the turnover of many cellular
      proteins and represents an attractive target for the treatment of pathologies
      such as cancer, as well as inflammatory, immune and neurodegenerative diseases.
      Natural and synthetic proteasome inhibitors having different chemical structures
      and potency have been discovered. We report herein the synthesis, proteasome
      inhibition and modelling studies of novel C-terminal isoxazoline vinyl ester
      pseudopeptides. Some new compounds that contain a C-terminal extended conjugation
      inhibit beta1 and especially beta5 proteasomal catalytic subunits with IC50
      values ranging from 10 to 100 um. These results will permit further optimization
      based on these structural moieties to develop more active and selective
      molecules.

PMID- 24677766
TI  - Roger Eric Marchant, Ph.D.: March 8, 1951--January 31, 2014.

PMID- 24677767
TI  - Novel porous scaffolds of pH responsive chitosan/carrageenan-based
      polyelectrolyte complexes for tissue engineering.
AB  - Polyelectrolyte complexes (PECs) represent promising materials for drug delivery
      and tissue engineering applications. These substances are obtained in aqueous
      medium without the need for crosslinking agents. PECs can be produced through the
      combination of oppositely charged medical grade polymers, which include the
      stimuli responsive ones. In this work, three-dimensional porous scaffolds were
      produced through the lyophilization of pH sensitive PECs made of chitosan (CS)
      and carrageenan (CRG). CS:CRG molar ratios of 1:1 (CSCRG1), 2:1 (CSCRG2), and 3:1
      (CSCRG3) were used. The chemical compositions of the PECs, as well as their
      influence in the final structure of the scaffolds were meticulously studied. In
      addition, the pH responsiveness of the PECs in a range including the
      physiological pH values of 7.4 (simulating normal physiological conditions) and
      4.5 (simulating inflammatory response) was assessed. Results showed that the PECs
      produced were stable at pH values of 7.4 and under but dissolved as the pH
      increased to nonphysiological values of 9 and 11. However, after dissolution, the
      PEC could be reprecipitated by decreasing the pH to values close to 4.5. The
      scaffolds obtained presented large and interconnected pores, being equally
      sensitive to changes in the pH. CSCRG1 scaffolds appeared to have higher
      hydrophilicity and therefore higher water absorption capacity. The increase in
      the CS:CRG molar ratios improved the scaffold mechanical properties, with CSCRG3
      presenting the higher compressive modulus under wet conditions. Overall, the PEC
      scaffolds appear promising for tissue engineering related applications that
      require the use of pH responsive materials stable at physiological conditions.

PMID- 24677768
TI  - DTB Select: 4 | April 2014.
AB  - Every month, DTB scans sources of information on treatments, disease management
      and other healthcare topics for key items to bring to our readers' attention and
      help them keep up to date. To do this, we produce succinct, contextualised
      summaries of the information concerned. We also include comments on, for example,
      the strengths of the information, whether it contains anomalies, ambiguities,
      apparent error or omissions, or whether or how it affects current practice.

PMID- 24677769
TI  - An efficient and modular route to sequence-defined polymers appended to DNA.
AB  - Inspired by biological polymers, sequence-controlled synthetic polymers are
      highly promising materials that integrate the robustness of synthetic systems
      with the information-derived activity of biological counterparts. Polymer
      biopolymer conjugates are often targeted to achieve this union; however, their
      synthesis remains challenging. We report a stepwise solid-phase approach for the
      generation of completely monodisperse and sequence-defined DNA-polymer conjugates
      using readily available reagents. These polymeric modifications to DNA display
      self-assembly and encapsulation behavior-as evidenced by HPLC, dynamic light
      scattering, and fluorescence studies-which is highly dependent on sequence order.
      The method is general and has the potential to make DNA-polymer conjugates and
      sequence-defined polymers widely available. 

PMID- 24677770
TI  - Anodic nanotubular/porous hematite photoanode for solar water splitting:
      substantial effect of iron substrate purity.
AB  - Anodization of iron substrates is one of the most simple and effective ways to
      fabricate nanotubular (and porous) structures that could be directly used as a
      photoanode for solar water splitting. Up to now, all studies in this field
      focused on achieving a better geometry of the hematite nanostructures for a
      higher efficiency. The present study, however, highlights that the purity of the
      iron substrate used for any anodic-hematite-formation approach is extremely
      important in view of the water-splitting performance. Herein, anodic self
      organized oxide morphologies (nanotubular and nanoporous) are grown on different
      iron substrates under a range of anodization conditions, including elevated
      temperatures and anodization supported by ultrasonication. Substrate purity has
      not only a significant effect on oxide-layer growth rate and tube morphology, but
      also gives rise to a ninefold increase in the photoelectrochemical water
      splitting performance (0.250 vs. 0.028 mA cm-2 at 1.40 V vs. reversible hydrogen
      electrode under AM 1.5 100 mW cm-2 illumination) for 99.99 % versus 99.5 % purity
      iron substrates of similar oxide geometry. Elemental analysis and model alloys
      show that particularly manganese impurities have a strong detrimental effect on
      the water-splitting performance.

PMID- 24677771
TI  - Fungal secretomes enhance sugar beet pulp hydrolysis.
AB  - The recalcitrance of lignocellulose makes enzymatic hydrolysis of plant biomass
      for the production of second generation biofuels a major challenge. This work
      investigates an efficient and economic approach for the enzymatic hydrolysis of
      sugar beet pulp (SBP), which is a difficult to degrade, hemicellulose-rich by
      product of the table sugar industry. Three fungal strains were grown on different
      substrates and the production of various extracellular hydrolytic and oxidative
      enzymes involved in pectin, hemicellulose, and cellulose breakdown were
      monitored. In a second step, the ability of the culture supernatants to hydrolyze
      thermally pretreated SBP was tested in batch experiments. The supernatant of
      Sclerotium rolfsii, a soil-borne facultative plant pathogen, was found to have
      the highest hydrolytic activity on SBP and was selected for further hydrolyzation
      experiments. A low enzyme load of 0.2 mg g(-1) protein from the culture
      supernatant was sufficient to hydrolyze a large fraction of the pectin and
      hemicelluloses present in SBP. The addition of Trichoderma reesei cellulase (1
      17.5 mg g(-1) SBP) resulted in almost complete hydrolyzation of cellulose. It was
      found that the combination of pectinolytic, hemicellulolytic, and cellulolytic
      activities works synergistically on the complex SBP composite, and a combination
      of these hydrolytic enzymes is required to achieve a high degree of enzymatic SBP
      hydrolysis with a low enzyme load. 

PMID- 24677772
TI  - Enantiodifferentiation through frequency-selective pure-shift (1)H nuclear
      magnetic resonance spectroscopy.
AB  - A frequency-selective 1D (1) H nuclear magnetic resonance (NMR) experiment for
      the fast and sensitive determination of chemical-shift differences between
      overlapped resonances is proposed. The resulting fully homodecoupled (1) H NMR
      resonances appear as resolved 1D singlets without their typical J(HH) coupling
      constant multiplet structures. The high signal dispersion that is achieved is
      then exploited in enantiodiscrimination studies by using chiral solvating agents.

PMID- 24677773
TI  - Selective detection of target proteins by peptide-enabled graphene biosensor.
AB  - Direct molecular detection of biomarkers is a promising approach for diagnosis
      and monitoring of numerous diseases, as well as a cornerstone of modern molecular
      medicine and drug discovery. Currently, clinical applications of biomarkers are
      limited by the sensitivity, complexity and low selectivity of available indirect
      detection methods. Electronic 1D and 2D nano-materials such as carbon nanotubes
      and graphene, respectively, offer unique advantages as sensing substrates for
      simple, fast and ultrasensitive detection of biomolecular binding. Versatile
      methods, however, have yet to be developed for simultaneous functionalization and
      passivation of the sensor surface to allow for enhanced detection and selectivity
      of the device. Herein, we demonstrate selective detection of a model protein
      against a background of serum protein using a graphene sensor functionalized via
      self-assembling multifunctional short peptides. The two peptides are engineered
      to bind to graphene and undergo co-assembly in the form of an ordered
      monomolecular film on the substrate. While the probe peptide displays the
      bioactive molecule, the passivating peptide prevents non-specific protein
      adsorption onto the device surface, ensuring target selectivity. In particular,
      we demonstrate a graphene field effect transistor (gFET) biosensor which can
      detect streptavidin against a background of serum bovine albumin at less than 50
      ng/ml. Our nano-sensor design, allows us to restore the graphene surface and
      utilize each sensor in multiple experiments. The peptide-enabled gFET device has
      great potential to address a variety of bio-sensing problems, such as studying
      ligand-receptor interactions, or detection of biomarkers in a clinical setting. 

PMID- 24677774
TI  - Amelioration of the typical cognitive phenotype in a patient with the 5pter
      deletion associated with Cri-du-chat syndrome in addition to a partial
      duplication of CTNND2.
AB  - Cri-du-chat is a rare congenital syndrome characterized by intellectual
      disability, severe speech/developmental delay, dysmorphic features, and
      additional syndromic findings. The etiology of this disorder is well known, and
      is attributed to a large deletion on chromosome 5 that typically ranges from band
      5p15.2 to the short arm terminus. This region contains CTNND2, a gene encoding a
      neuronal-specific protein, delta-catenin, which plays a critical role in cellular
      motility and brain function. The exact involvement of CTNND2 in the cognitive
      functionality of individuals with Cri-du-chat has not been fully deciphered, but
      it is thought to be significant. This report describes an 8-year-old African
      American female with a complex chromosome 5 abnormality and a relatively mild
      case of cri-du-chat syndrome. Because of the surprisingly mild cognitive
      phenotype, although a karyotype had confirmed the 5p deletion at birth, an oligo
      SNP microarray was obtained to further characterize her deletion. The array
      revealed a complex rearrangement, including a breakpoint in the middle of CTNND2,
      which resulted in a partial deletion and partial duplication of that gene. The
      array also verified the expected 5p terminal deletion. Although the patient has a
      significant deletion in CTNND2, half of the gene (including the promoter region)
      is not only preserved, but is duplicated. The patient's milder cognitive and
      behavioral presentation, in conjunction with her atypical 5p alteration, provides
      additional evidence for the role of CTNND2 in the cognitive phenotype of
      individuals with Cri-du-chat.

PMID- 24677776
TI  - Case study interpretation--Fort Lauderdale: Case 3.

PMID- 24677777
TI  - Constructing 3D branched nanowire coated macroporous metal oxide electrodes with
      homogeneous or heterogeneous compositions for efficient solar cells.
AB  - Light-harvesting and charge collection have attracted increasing attention in the
      domain of photovoltaic cells, and can be facilitated dramatically by appropriate
      design of a photonic nanostructure. However, the applicability of current light
      harvesting photoanode materials with single component and/or morphology (such as,
      particles, spheres, wires, sheets) is still limited by drawbacks such as
      insufficient electron-hole separation and/or light-trapping. Herein, we introduce
      a universal method to prepare hierarchical assembly of macroporous material
      nanowire coated homogenous or heterogeneous metal oxide composite electrodes
      (TiO2 -TiO2 , SnO2 -TiO2 , and Zn2 SnO4 -TiO2 ; homogenous refers to a material
      in which the nanowire and the macroporous material have the same composition,
      i.e. both are TiO2 . Heterogeneous refers to a material in which the nanowires
      and the macroporous material have different compositions). The dye-sensitized
      solar cell based on a TiO2 -macroporous material-TiO2 -nanowire homogenous
      composition electrode shows an impressive conversion efficiency of 9.51 %, which
      is much higher than that of pure macroporous material-based photoelectrodes to
      date. 

PMID- 24677775
TI  - Anchoring a cytoactive factor in a wound bed promotes healing.
AB  - Wound healing is a complex process that requires the intervention of cytoactive
      factors. The one-time application of soluble factors to a wound bed does not
      maintain a steady, sufficient concentration. Here we investigated the benefits of
      anchoring a factor in a wound bed via a tether to endogenous collagen. We used a
      collagen-mimetic peptide (CMP) as a pylon. The CMP binds to damaged but not
      intact collagen and thus localizes a pendant cytoactive factor in the regions of
      a wound bed that require intervention. As a model factor, we chose substance P, a
      peptide of the tachykinin family that promotes wound healing. Using splinted
      wounds in db/db mice, we found that the one-time application of a CMP-substance P
      conjugate enhances wound healing compared to unconjugated substance P and other
      controls. Specifically, all 16 wounds treated with the conjugate closed more
      thoroughly and, did so with extensive re-epithelialization and mitigated
      inflammatory activity. These data validate a simple and general strategy for re
      engineering wound beds by the integration of beneficial cytoactive factors.
      Copyright (c) 2014 John Wiley & Sons, Ltd.

PMID- 24677778
TI  - Ethanol extract of Hedyotis diffusa willd upregulates G0/G1 phase arrest and
      induces apoptosis in human leukemia cells by modulating caspase cascade signaling
      and altering associated genes expression was assayed by cDNA microarray.
AB  - The authors' previous study has shown that water extract of Hedyotis diffusa
      Willd (HDW) promoted immune response and exhibited anti-leukemic activity in
      BALB/c leukemic mice in vivo. In this study, the anti-proliferation effects of
      ethanol extract of H. diffusa Willd (EEHDW) on lung cancer cell lines (A549,
      H1355, and LLC), leukemia cell lines (HL-60, WEHI-3), and a mouse melanoma cell
      line (B16F10) in vitro were investigated. The results demonstrated that EEHDW
      suppressed the cell proliferation of A549, H1355, HL-60, WEHI-3, and B16F10 cells
      as well as reduced cell viability in a concentration-dependent manner. We found
      that EEHDW inhibited the cell proliferation of HL-60 cells in concentration
      dependent manner. In addition, EEHDW triggered an arrest of HL-60 cells at G0/G1
      phase and sub-G1 population (apoptotic cells). EEHDW provoked DNA condensation
      and DNA damage in HL-60 cells. The activities of caspase-3, caspase-8, and
      caspase-9 were elevated in EEHDW-treated HL-60 cells. DNA microarray to
      investigate and display the gene levels related to cell growth, signal
      transduction, apoptosis, cell adhesion, cell cycle, DNA damage and repair,
      transcription and translation was also used. These findings suggest that EEHDW
      may be a potential herbal medicine and therapeutic agent for the treatment of
      leukemia.

PMID- 24677779
TI  - Cytotoxic gold(I) N-heterocyclic carbene complexes with phosphane ligands as
      potent enzyme inhibitors.
AB  - Organometallic gold complexes with N-heterocyclic carbene (NHC) ligands have been
      demonstrating promising properties as novel anticancer agents. Gold(I) NHC
      complexes containing different phosphanes as secondary ligands were shown to
      trigger strong cytotoxic effects in cancer cells, and their effective uptake into
      the cells was quantified by atomic absorption spectroscopy. Moreover, the new
      compounds strongly inhibited the activity of the seleno-enzyme thioredoxin
      reductase (TrxR) and of the zinc-finger enzyme poly(ADP-ribose) polymerase 1
      (PARP-1). In the case of TrxR inhibition, their activity depended clearly on the
      size of the alkyl/aryl residues of phosphorus atoms. Density functional theory
      (DFT) calculations showed that the Au-P bond of the triphenylphosphane complex
      [Au(I) (NHC)(PPh3 )]I had a lower bond dissociation energy compared to
      trialkylphosphane complexes [Au(I) (NHC)(PR3 )]I, indicating a higher kinetic
      reactivity of this particular compound. In fact, [Au(I) (NHC)(PPh3 )]I triggered
      an enhanced inhibitory activity against PARP-1.

PMID- 24677780
TI  - Maize (Zea mays L.) seedling leaf nuclear proteome and differentially expressed
      proteins between a hybrid and its parental lines.
AB  - To better understand the underlying molecular basis of leaf development in maize,
      a reference map of nuclear proteins in basal region of seedling leaf was
      established using a combination of 2DE and MALDI-TOF-MS. In total, 441
      reproducible protein spots in nuclear proteome of maize leaf basal region were
      detected with silver staining in a pH range of 3-10, among which 203 spots
      corresponding to 163 different proteins were identified. As expected, proteins
      implicated in RNA and protein-associated functions were overrepresented in
      nuclear proteome. Remarkably, a high percentage (10%) of proteins was identified
      to be involved in cell division and growth. In addition, comparative nuclear
      proteomic analysis in leaf basal region of highly heterotic hybrid Mo17/B73 and
      its parental lines was also performed and 52 of 445 (11.69%) detected protein
      spots were differentially expressed between the hybrid and its parental lines,
      among which 16 protein spots displayed nonadditively expressed pattern. These
      results indicated that hybridization between two parental lines can cause changes
      in the expression of a variety of nuclear proteins, which may be responsible for
      the observed leaf size heterosis. 

PMID- 24677781
TI  - Anticancer potency of small linear and cyclic tetrapeptides and pharmacokinetic
      investigations of peptide binding to human serum albumin.
AB  - We have in the present study explored the anticancer activity against human
      Burkitt's lymphoma cells (Ramos) of a series of small linear and cyclic
      tetrapeptides containing a beta2,2-amino acid with either two 2-naphthyl
      methylene or two para-CF3-benzyl side chains, along with their interaction with
      the main plasma protein human serum albumin (HSA). The cyclic and more
      amphipathic tetrapeptides revealed a notably higher anticancer potency against
      Ramos cells [50% inhibitory concentration (IC50) 11-70 MUM] compared to the
      linear tetrapeptide counterparts (IC50 18.7 to >413 MUM). The most potent cyclic
      tetrapeptide c3 had a 16.5-fold preference for Ramos cells compared to human red
      blood cells, whereas the cyclic tetrapeptide c1 both showed low hemolytic
      activity and displayed the overall highest (2.9-fold) preference for Ramos cells
      (IC50 23 MUM) compared to healthy human lung fibroblast cells (MRC-5).
      Investigating the interaction of selected tetrapeptides and recently reported
      hexapeptides with HSA revealed that the peptides bind to drug site II of HSA in
      the 22-28 MUM range, disregarding size and overall structure. NMR and in silico
      molecular docking experiments identified the lipophilic residues as responsible
      for the interaction, but in vitro studies showed that the anticancer potency of
      the peptides varied in the presence of HSA and that c3 remained the most potent
      peptide. Based on our findings, we call for implementing serum albumin binding in
      development of anticancer peptides, as it may have implications for future
      administration and systemic distribution of peptide-based cancer drugs.

PMID- 24677782
TI  - Transvenous valve-in-valve replacement preserving the function of a transvalvular
      defibrillator lead.
AB  - Although feasibility and efficacy of percutaneous tricuspid valve-in-valve
      implantation have been established, a transtricuspid pacing or defibrillator lead
      might preclude this technique: lead damage can cause lead dysfunction resulting
      in inappropriate or inefficient pacing or shocks. In these cases, lead removal is
      thought to be the only option. We describe a patient who presented with rapid
      clinical deterioration due to tricuspid valve stenosis early after implantation
      of an internal defibrillator with a transvalvular shock-lead. A transvenous valve
      in-valve implantation of the tricuspid valve was performed after protecting the
      defibrillator-lead with a custom-made covered stent. We describe the technical
      issues, the clinical outcome, and the evolution of lead function after
      implantation.

PMID- 24677783
TI  - Effects of functionalization of PLGA-[Asp-PEG]n copolymer surfaces with Arg-Gly
      Asp peptides, hydroxyapatite nanoparticles, and BMP-2-derived peptides on cell
      behavior in vitro.
AB  - Functionalization of polymer surfaces has been recognized as a valuable tool to
      improve their properties that significantly influence cellular behaviors, such as
      adhesion, proliferation, migration, and differentiation. In stem cell-mediated
      bone tissue engineering, surface multifunctionalization of polymeric scaffolds
      with cell-adhesive, osteoconductive, and osteoinductive biomolecules is a
      critical strategy to improve such properties. However, the traditional surface
      modification techniques such as physical deposition/adsorption, chemical
      modification, grafting, and plasma techniques have great limitations for
      immobilization of multiple bioactive molecules due to multistep procedures.
      Recently, a universal technique based on mussel-inspired self-polymerization of
      dopamine is developed for multifunctional coatings in a simple way. In our study,
      we used this newly developed technique to incorporate three biomolecules, cell
      adhesion-promoting (K)16 GRGDSPC peptides, osteoconductive hydroxyapatite (HAp)
      nanoparticles, and osteoinductive bone morphogenetic protein-2-derived P24
      peptides, to functionalize poly(lactide-co-glycolide) (PLGA)-[Asp-PEG]n
      scaffolds, and the effects on biological behaviors of co-cultured rabbit-derived
      bone marrow stromal cells in vitro were investigated. The results showed (K)16
      GRGDSPC, HAp, and P24 could be immobilized onto the scaffolds through
      predeposition of polydopamine (pDA) ad-layer, and the surface-modified scaffolds
      were noncytotoxic as well as the virgin scaffold. The pDA-assisted codeposition
      of (K)16 GRGDSPC, HAp, and P24 on the scaffold surfaces significantly promoted
      cell adhesion, proliferation, osteodifferentiation, and mineralization in vitro
      with synergistic effects. Taken together, the functionalized PLGA-[Asp-PEG]n
      polymeric scaffolds achieved significantly elevated affinity, osteoconductive and
      osteoinductive ability, and may be a potentially promising bone graft substitute
      for bone repair.

PMID- 24677784
TI  - Amine-functionalized amino acid-based ionic liquids as efficient and high
      capacity absorbents for CO(2).
AB  - Ionic liquids (ILs) comprised of ammonium cations and anions of naturally
      occurring amino acids containing an additional amine group (e.g., lysine,
      histidine, asparagine, and glutamine) were examined as high-capacity absorbents
      for CO2. An absorption capacity of 2.1 mol CO2 per mol of IL (3.5 mol CO2 per kg
      IL, 13.1 wt% CO2) was measured for [N66614][Lys] at ambient temperature and about
      1 mol CO2 per mol of IL at 808C (under 1 bar of CO2). This demonstrated that
      desorption is possible under CO2-rich conditions by temperature-swing absorption;
      three consecutive sorption cycles were performed with the IL. The mechanistic and
      kinetic study of the absorption process was further substantiated by NMR
      spectroscopy and in situ attenuated total reflectance FTIR for [N66614][Lys] and
      the homologous phosphonium-based IL [P66614][Lys]. This study revealed that
      carbamic acid was formed with CO2 in both ILs by chemisorption; however, the
      amino acid-carboxyl groups on the anion played an important-but different
      catalytic role for the sorption kinetics in the two ILs. The origin of the
      cationic effect is speculated to be correlated with the strength of the ion
      interactions in the two ILs.

PMID- 24677786
TI  - Extensive scheduled CT and CEA follow-up are equivalent in detecting recurrent
      colorectal cancer that is surgically treatable with curative intent, and superior
      to minimal follow up.

PMID- 24677785
TI  - Robust, microfabricated culture devices with improved control over the soluble
      microenvironment for the culture of embryonic stem cells.
AB  - The commercial use of stem cells continues to be constrained by the difficulty
      and high cost of developing efficient and reliable production protocols. The use
      of microfabricated systems combines good control over the cellular
      microenvironment with reduced use of resources in process optimization. Our
      previously reported microfabricated culture device was shown to be suitable for
      the culture of embryonic stem cells but required improvements to robustness, ease
      of use, and dissolved gas control. In this report, we describe a number of
      improvements to the design of the microfabricated system to significantly improve
      the control over shear stress and soluble factors, particularly dissolved oxygen.
      These control improvements are investigated by finite element modeling. Design
      improvements also make the system easier to use and improve the robustness. The
      culture device could be applied to the optimization of pluripotent stem cell
      growth and differentiation, as well as the development of monitoring and control
      strategies and improved culture systems at various scales. 

PMID- 24677787
TI  - Chromosomal-array analysis reveals partial 11q duplication and partial 12p
      deletion in a mildly affected case.
AB  - Partial trisomy 11q is a rare syndrome and may be observed due to an intra
      chromosomal duplication or an inter-chromosomal insertion. The deletions of the
      short arm of chromosome 12 are also uncommon structural aberrations. Only a small
      fraction of structural chromosome anomalies are related to the unbalanced progeny
      of balanced translocation carrier parents. We here report on a 10-month-old baby
      boy who shows a very mild phenotype related to unique chromosomal abnormality,
      partial trisomy of 11q, and partial monosomy of 12p, due to the maternal balanced
      reciprocal translocation (11;12). The proband showed a 49.64 Mb duplication of
      11q14.1-q25 and 0.44 Mb deletion of 12p13.33 in chromosomal array analysis. Since
      it is known that the duplications may cause a milder phenotype than deletions.
      Dysmorphic facial features, minor cardiac anomalies, respiratory distress,
      central nervous system anomalies, and psychomotor delay observed in the patient
      was similar to the reported pure 11q duplication cases, while behavioral problems
      observed in pure monosomy 12p cases could not be evaluated due to the young age
      of the patient. Phenotype-genotype correlation will be discussed in view of all
      the reported pure partial 11q trisomies and pure partial 12p deletion cases.

PMID- 24677788
TI  - Influence of spiral framework on nonlinear optical materials.
AB  - A series of spiral donor-pi-acceptor frameworks (i.e. 2-2, 3-3, 4-4, and 5-5)
      based on 4-nitrophenyldiphenylamine with pi-conjugated linear acenes
      (naphthalenes, anthracenes, tetracenes, and pentacenes) serving as the electron
      donor and nitro (NO2 ) groups serving as the electron acceptor were designed to
      investigate the relationships between the nonlinear optical (NLO) responses and
      the spirality in the frameworks. A parameter denoted as D was defined to describe
      the extent of the spiral framework. The D value reached its maximum if the number
      of NO2 groups was equal to the number of fused benzene rings contained in the
      linear acene. A longer 4-nitrophenyldiphenylamine chain led to a larger D value
      and, further, to a larger first hyperpolarizability. Different from traditional
      NLO materials with charge transfer occurring in the one-dimensional direction,
      charge transfer in 2-2, 3-3, 4-4, and 5-5 occur in three-dimensional directions
      due to the attractive spiral frameworks, and this is of great importance in the
      design of NLO materials. The origin of such an enhancement in the NLO properties
      of these spiral frameworks was explained with the aid of molecular orbital
      analysis. 

PMID- 24677789
TI  - Decreased generation of procoagulant platelets detected by flow cytometric
      analysis in patients with bleeding diathesis.
AB  - BACKGROUND: A clinically relevant bleeding diathesis is a frequent diagnostic
      challenge, which sometimes remains unexplained despite extensive investigations.
      The aim of our work was to evaluate the diagnostic utility of functional platelet
      testing by flow cytometry in this context. METHODS: In case of negative results
      after standard laboratory workup, flow cytometric analysis (FCA) of platelet
      function was done. We performed analysis of surface glycoproteins Ibalpha, IIb,
      IIIa; P-selectin expression and PAC-1 binding after graded doses of ADP,
      collagen, and thrombin; content/secretion of dense granules; and ability to
      generate procoagulant platelets. RESULTS: Of 437 patients investigated with
      standard tests between January 2007 and December 2011, we identified 67 (15.3%)
      with high bleeding scores and nondiagnostic standard laboratory workup including
      platelet aggregation studies. Among these patients, FCA revealed some potentially
      causative platelet defects: decreased dense granule content/secretion (n = 13);
      decreased alpha-granule secretion induced by ADP (n = 10), convulxin (n = 4), or
      thrombin (n = 3); decreased fibrinogen receptor activation induced by ADP (n =
      11), convulxin (n = 11), or thrombin (n = 8); and decreased generation of COAT
      platelets, that is, highly procoagulant platelets induced by simultaneous
      activation with collagen and thrombin (n = 16). CONCLUSION: Our work confirms
      that storage pool defects are frequent in patients with a bleeding diathesis and
      normal coagulation and platelet aggregations studies. Additionally, FCA is able
      to identify discrete platelet activation defects. In particular, we show for the
      first time that a relevant proportion of these patients has an isolated impaired
      ability to generate COAT platelets--a conceptually new defect in platelet
      procoagulant activity, which is missed by conventional laboratory workup.

PMID- 24677790
TI  - Renin angiotensin system inhibitors may attenuate low LDL cholesterol-related
      cancer risk in type 2 diabetes.
AB  - BACKGROUND: In type 2 diabetes (T2D), copresence of low-density lipoprotein
      cholesterol (LDL-C) < 2.8 mmol/L with triglyceride < 1.7 mmol/L or with
      albuminuria synergistically increased cancer risk. We tested whether use of renin
      angiotensin system inhibitors attenuated the increased cancer risk associated
      with these two risk subphenotypes. METHODS: A prospective cohort of 4307 patients
      with T2D enrolled from December 1996 to January 2005 was analysed using a new
      user cohort design. Cox model analysis was used to obtain hazard ratios and 95%
      confidence intervals. The study measured additive interactions between nonuse of
      renin angiotensin system inhibitors and low LDL-C plus low triglyceride or
      albuminuria for the risk of cancer. A positive interaction suggests a specific
      drug effect on the low LDL-C-related cancer risk. RESULTS: During 18 769 person
      years of follow-up (median follow-up years: 4.44), 4.48% (n = 193) of patients
      developed cancer. Use of renin angiotensin system inhibitors was associated with
      reduced cancer risk among patients with copresence of low LDL-C plus low
      triglyceride or low LDL-C plus albuminuria but not in patients without these
      subphenotypes. In multivariable analysis, renin angiotensin system inhibitor
      usage attenuated the hazard ratio of copresence of low LDL-C plus low
      triglyceride versus lack of this subphenotype for cancer from 2.08 (95% CI: 1.25
      3.47) to 1.13 (0.61-2.11) with significant additive interaction (p = 0.0225).
      Similarly, RAS inhibitor usage attenuated the hazard ratio of copresence of low
      LDL-C plus albuminuria versus lack of this subphenotype for cancer from 1.99 (95%
      CI: 1.12-3.56) to 0.82 (0.43-1.54) with significant additive interaction (p =
      0.0009). CONCLUSION: In T2D, renin angiotensin system inhibitor usage may
      specifically attenuate the low LDL-C-related cancer risk.

PMID- 24677791
TI  - The In Vivo Radiosensitizing Effect of Gold Nanoparticles Based MRI Contrast
      Agents.
AB  - Owing to the high atomic number (Z) of gold element, the gold nanoparticles
      appear as very promising radiosensitizing agents. This character can be exploited
      for improving the selectivity of radiotherapy. However, such an improvement is
      possible only if irradiation is performed when the gold content is high in the
      tumor and low in the surrounding healthy tissue. As a result, the beneficial
      action of irradiation (the eradication of the tumor) should occur while the
      deleterious side effects of radiotherapy should be limited by sparing the healthy
      tissue. The location of the radiosensitizers is therefore required to initiate
      the radiotherapy. Designing gold nanoparticles for monitoring their distribution
      by magnetic resonance imaging (MRI) is an asset due to the high resolution of MRI
      which permits the accurate location of particles and therefore the determination
      of the optimal time for the irradiation. We recently demonstrated that ultrasmall
      gold nanoparticles coated by gadolinium chelates (Au@DTDTPA-Gd) can be followed
      up by MRI after intravenous injection. Herein, Au@DTDTPA and Au@DTDTPA-Gd were
      prepared in order to evaluate their potential for radiosensitization. Comet
      assays and in vivo experiments suggest that these particles appear well suited
      for improving the selectivity of the radiotherapy. The dose which is used for
      inducing similar levels of DNA alteration is divided by two when cells are
      incubated with the gold nanoparticles prior to the irradiation. Moreover, the
      increase in the lifespan of tumor bearing rats is more important when the
      irradiation is performed after the injection of the gold nanoparticles. In the
      case of treatment of rats with a brain tumor (9L gliosarcoma, a radio-resistant
      tumor in a radiosensitive organ), the delay between the intravenous injection and
      the irradiation was determined by MRI.

PMID- 24677793
TI  - Optical devices constructed from multiresponsive microgels.
AB  - Novel multiresponsive microgels based on poly(N-isopropylacrylamide) were
      synthesized to contain triphenylmethane leucohydroxide, and used to construct
      etalons. The optical properties of the resultant etalons were investigated, and
      their response to ultraviolet and visible irradiation, solution pH changes, and
      the presence of a mimic of the nerve agent Tabun characterized. We clearly show
      that the optical properties of the device depended dramatically on these stimuli.
      This investigation illustrates the versatility of the microgel-based etalon
      structure, and showcases the clear utility of such devices for remote actuation,
      color tunable optics, sensing, and potential remotely triggered drug delivery
      applications. 

PMID- 24677792
TI  - Design, synthesis and bioevaluation of an EphA2 receptor-based targeted delivery
      system.
AB  - Because of its overexpression in a range of solid tumors, the EphA2 receptor is a
      validated target for cancer therapeutics. We recently described a new targeted
      delivery system based on specific EphA2-targeting peptides conjugated with the
      chemotherapeutic agent paclitaxel. Here, we investigate the chemical determinants
      responsible for the stability and degradation of these agents in plasma.
      Introducing modifications in both the peptide and the linker between the peptide
      and paclitaxel resulted in drug conjugates that are both long-lived in rat plasma
      and that markedly decrease tumor size in a prostate cancer xenograft model
      compared with paclitaxel alone treatment. These studies identify critical rate
      limiting degradation sites on the peptide-drug conjugates, enabling the design of
      agents with increased stability and efficacy. These results provide support for
      our central hypothesis that peptide-drug conjugates targeting EphA2 represent an
      innovative and potentially effective strategy to selectively deliver cytotoxic
      drugs to cancer cells. 

PMID- 24677795
TI  - An experimental strategy for the identification of AMPylation targets from
      complex protein samples.
AB  - AMPylation is a posttranslational modification (PTM) that has recently caught
      much attention in the context of bacterial infections as pathogens were shown to
      secrete Fic proteins that AMPylate Rho GTPases and thus interfere with host cell
      signaling processes. Although Fic proteins are widespread and found in all
      kingdoms of life, only a small number of AMPylation targets are known to date. A
      major obstacle to target identification is the limited availability of generic
      strategies allowing sensitive and robust identification of AMPylation events.
      Here, we present an unbiased MS-based approach utilizing stable isotope-labeled
      ATP. The ATP isotopes are transferred onto target proteins in crude cell lysates
      by in vitro AMPylation introducing specific reporter ion clusters that allow
      detection of AMPylated peptides in complex biological samples by MS analysis.
      Applying this strategy on the secreted Fic protein Bep2 of Bartonella rochalimae,
      we identified the filamenting protein vimentin as an AMPylation target that was
      confirmed by independent assays. Vimentin represents a new class of target
      proteins and its identification emphasizes our method as a valuable tool to
      systematically uncover AMPylation targets. Furthermore, the approach can be
      generically adapted to study targets of other PTMs that allow incorporation of
      isotopically labeled substrates. 

PMID- 24677796
TI  - Correlation of the intracellular reactive oxygen species levels with textural
      properties of functionalized mesostructured silica.
AB  - Mesostructured silica is frequently used in biomedical applications, being
      considered nontoxic and biocompatible material, suitable for the development of
      drug delivery systems (DDS). Four functionalized MCM-41 silica materials with
      hydrophobic (methyl and vinyl) and hydrophilic (3-aminopropyl and 3
      mercaptopropyl) groups were obtained by post-synthesis functionalization and
      characterized by small-angle X-ray diffraction, infrared spectroscopy, thermal
      analysis, and nitrogen adsorption-desorption isotherms. The main structural and
      textural parameters of the obtained silica were determined. The effect of the
      functionalized silica on fibroblast (NIH3T3) and melanocyte cells (B16F10) was
      studied with respect to the proliferation rate and the levels of reactive oxygen
      species (ROS). It was found that the textural properties of all samples
      influenced the levels of intracellular ROS and consequently, the proliferation
      rate. Both, healthy and malignant cells exhibited linear dependence of ROS levels
      with the specific surface area values, but with different response. The
      contribution of the methyl functionalized silica to the ROS level is apart to the
      general trend.

PMID- 24677797
TI  - Perventricular closure of pulmonary stump in a 16-kg child.
AB  - Blind pouch formation of the pulmonary artery (PA) in patients having undergone a
      Fontan operation can present a serious risk for thromboembolic events. Either
      primary or secondary closure of this stump is necessary to reduce this risk.
      Unfortunately, secondary closure is oftentimes difficult due to the size and
      anatomy of the presenting patient. We describe the insertion of a muscular
      ventricular septal defect (VSD) device via a perventricular approach for
      successful closure of a pulmonary stump in a 3-year old, 16-kg child. To our
      knowledge, this is the first report of a perventricular approach for successful
      closure of a PA stump.

PMID- 24677798
TI  - Aerobic expression of Vitreoscilla hemoglobin efficiently reduces overflow
      metabolism in Escherichia coli.
AB  - Overflow metabolism is a prevalent problem for aerobic cultivations of
      Escherichia coli. Although several process and molecular approaches have been
      applied to prevent overflow metabolism, these approaches often result in
      reductions in growth rate, biomass yield or accumulation of other byproducts. In
      this report, we present an alternative approach based on increasing the
      efficiency of aerobic metabolism by the expression of the Vitreoscilla
      stercoraria hemoglobin (VHb) to avoid overflow metabolism. VHb is expected to
      increase the consumption of NADH in the respiratory chain, leading to increased
      activity of the tricarboxylic acid (TCA) cycle. This would result in a faster
      consumption of acetyl Co-A and a decrease in acetate production. When this
      strategy was tested in E. coli strains, acetate production decreased by 50% in
      MG1655 and more than 90% in W3110, without affecting growth rates or biomass
      yields. VHb expression in mutant strains with higher TCA activity and reduced
      acetate formation resulted in a significant increase in growth and glucose
      consumption rates, whereas acetate production did not increase. The results
      presented here show that enhancing the efficiency of aerobic metabolism is a
      valuable approach to avoid overflow metabolism in E. coli and to attain high cell
      densities in batch mode. 

PMID- 24677799
TI  - Gas separation performance of carbon molecular sieve membranes based on 6FDA
      mPDA/DABA (3:2) polyimide.
AB  - 6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross
      linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The
      membranes were characterized with thermogravimetric analysis, FTIR spectroscopy,
      wide-angle X-ray diffraction, and gas permeation tests. Variations in the d
      spacing, the formation of pore structures, and changes in the pore sizes of the
      CMS membranes were discussed in relation to pyrolysis protocols. The uncross
      linked polymer membranes showed high CO2 /CH4 selectivity, whereas thermally
      crosslinked membranes exhibited significantly improved CO2 permeability and
      excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2
      permeability and CO2 /CH4 selectivity. An increase in the pyrolysis temperature
      resulted in CMS membranes with lower gas permeability but higher selectivity. The
      550  degrees C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750
      Barrer with CO2 /CH4 selectivity of approximately 52. Even 800  degrees C
      pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with
      high CO2 /CH4 selectivity of approximately 118. Both polymer membranes and the
      CMS membranes are very attractive in aggressive natural gas purification
      applications.

PMID- 24677800
TI  - Formation of a familial ring chromosome 18 investigated by SNP-array analysis.

PMID- 24677801
TI  - Role of dendritic cells in the context of acute cellular rejection: Comparison
      between Tacrolimus- or Cyclosporine A-treated heart transplanted recipients.

PMID- 24677802
TI  - RevErbalpha preferentially deforms DNA by induced fit.
AB  - Using free-energy simulations, we have shown that RevErbalpha-induced DNA
      deformation preferentially occurs by induced fit rather than by conformational
      selection, even though the DNA is only slightly distorted in the complex. Our
      study shows that information on the sequence of binding events is needed to
      establish whether conformational selection or induced fit is operative, and that
      the presence of multiple apo-state structures might not be enough to distinguish
      between these binding models

PMID- 24677803
TI  - Porous protein crystals as catalytic vessels for organometallic complexes.
AB  - Porous protein crystals, which are protein assemblies in the solid state, have
      been engineered to form catalytic vessels by the incorporation of organometallic
      complexes. Ruthenium complexes in cross-linked porous hen egg white lysozyme
      (HEWL) crystals catalyzed the enantioselective hydrogen-transfer reduction of
      acetophenone derivatives. The crystals accelerated the catalytic reaction and
      gave different enantiomers based on the crystal form (tetragonal or
      orthorhombic). This method represents a new approach for the construction of
      bioinorganic catalysts from protein crystals. 

PMID- 24677804
TI  - REM sleep twitches rouse nascent cerebellar circuits: Implications for
      sensorimotor development.
AB  - The cerebellum is critical for sensorimotor integration and undergoes extensive
      postnatal development. During the first postnatal week in rats, climbing fibers
      polyinnervate Purkinje cells and, before granule cell migration, mossy fibers
      make transient, direct connections with Purkinje cells. Activity-dependent
      processes are assumed to play a critical role in the development and refinement
      of these and other aspects of cerebellar circuitry. However, the sources and
      patterning of activity have not been described. We hypothesize that sensory
      feedback (i.e., reafference) from myoclonic twitches in sleeping newborn rats is
      a prominent driver of activity for the developing cerebellum. Here, in 6-day-old
      rats, we show that Purkinje cells exhibit substantial state-dependent changes in
      complex and simple spike activity-primarily during active sleep. In addition,
      this activity increases significantly during bouts of twitching. Moreover, the
      surprising observation of twitch-dependent increases in simple spike activity at
      this age suggests a functional engagement of mossy fibers before the parallel
      fiber system has developed. Based on these and other results, we propose that
      twitching comprises a unique class of self-produced movement that drives critical
      aspects of activity-dependent development in the cerebellum and other
      sensorimotor systems.

PMID- 24677806
TI  - MSDA, a proteomics software suite for in-depth Mass Spectrometry Data Analysis
      using grid computing.
AB  - One of the major bottlenecks in the proteomics field today resides in the
      computational interpretation of the massive data generated by the latest
      generation of high-throughput MS instruments. MS/MS datasets are constantly
      increasing in size and complexity and it becomes challenging to comprehensively
      process such huge datasets and afterwards deduce most relevant biological
      information. The Mass Spectrometry Data Analysis (MSDA, https://msda.unistra.fr)
      online software suite provides a series of modules for in-depth MS/MS data
      analysis. It includes a custom databases generation toolbox, modules for
      filtering and extracting high-quality spectra, for running high-performance
      database and de novo searches, and for extracting modified peptides spectra and
      functional annotations. Additionally, MSDA enables running the most
      computationally intensive steps, namely database and de novo searches, on a
      computer grid thus providing a net time gain of up to 99% for data processing. 

PMID- 24677805
TI  - Injectable redox-polymerized methylcellulose hydrogels as potential soft tissue
      filler materials.
AB  - There is a significant clinical need for long-lasting, injectable materials for
      soft tissue reconstruction. Methylcellulose (MC) is an FDA-approved
      polysaccharide derivative of cellulose that is inexpensive, renewable, and
      biocompatible, and may serve as an alternative to existing synthetic and natural
      fillers. In this study, MC was modified with functional methacrylate groups and
      polymerized using a redox-initiation system to produce hydrogels with tunable
      properties. By varying the percent methacrylation and macromer concentration, the
      equilibrium moduli of the hydrogels were found to range between 1.29 +/- 0.46 and
      12.8 +/- 2.94 kPa, on par with human adipose tissue, and also displayed an
      inverse relationship to the swelling properties. Rheological analyses determined
      gelation onset and completion to be in accordance with the ISO standard for
      injectable materials. Cellulase enzymatic treatment resulted in complete
      degradation of the hydrogels by 48 h, presenting the possibility of minimally
      invasive removal of the materials in the event of malposition or host reaction.
      In addition, co-culture experiments with human dermal fibroblasts showed the gels
      to be cytocompatible based on DNA measurements and Live/Dead staining. Taken
      together, these redox-polymerized MC hydrogels may be of use for a wide range of
      clinical indications requiring soft tissue augmentation.

PMID- 24677808
TI  - Role of additives in formation of solid-electrolyte interfaces on carbon
      electrodes and their effect on high-voltage stability.
AB  - The in situ modification of a lithium hexafluorophosphate-based electrolyte using
      a molybdenum oxide catalyst and small amount of water (1 vol %) yields hydrolysis
      products such as mono-, di-, and alkylfluorophosphates. The electrochemical
      stability of ultrahigh-purity, high-surface-area carbon electrodes derived from
      polyfurfuryl alcohol was tested using the modified electrolyte. Favorable
      modification of the solid electrolyte interface (SEI) layer on the activated
      carbon electrode increased the cyclable electrochemical voltage window (4.8-1.2 V
      vs. Li/Li(+)). The chemical modification of the SEI layer induced by electrolyte
      additives was characterized by using X-ray photoelectron spectroscopy.

PMID- 24677807
TI  - Using SV119-gold nanocage conjugates to eradicate cancer stem cells through a
      combination of photothermal and chemo therapies.
AB  - Cancer stem cells (CSCs) are believed to be responsible for the long-term growth
      of a tumor, as well as its metastasis and recurrence after conventional
      therapies. Here, it is demonstrated that the sigma-2 receptor is overexpressed on
      the surface of breast CSCs, and thus could serve as a biomarker for the purpose
      of targeting. Breast CSCs are targeted with Au nanocages (AuNCs) by
      functionalizing their surfaces with SV119, a synthetic small molecule capable of
      binding to the sigma-2 receptor with high specificity. The interiors of the AuNCs
      could also be loaded with an anticancer drug to be selectively delivered to
      breast CSCs and released in a controllable fashion. The results demonstrate that
      the SV119-AuNC conjugate can serve as a new platform to carry out photothermal
      and chemo therapies simultaneously, eradicating breast CSCs more effectively
      through a synergetic effect. 

PMID- 24677809
TI  - A combined cell-free transcription-translation system from Saccharomyces
      cerevisiae for rapid and robust protein synthe.
AB  - Cell-free protein synthesis (CFPS) provides a valuable platform for
      understanding, using, and expanding the capabilities of the translation
      apparatus. For example, high-throughput CFPS is helping to address the increasing
      discrepancy between genome sequence data and their translation products. Here, we
      report the development of a combined cell-free transcription-translation (Tx/Tl)
      system from Saccharomyces cerevisiae that is suitable for such efforts. First, we
      show the ability to enable translation initiation in a cap-independent manner.
      The performance of various genetic elements was assessed, including 5'-UTR, 3'
      UTR, and length of poly(A) tail. A specific vector harboring the 5'-UTR fragment
      of the Omega sequence from the tobacco mosaic virus and a poly(A) tail of 50
      nucleotides led to optimal performance. Second, we developed a simple, two-step
      polymerase chain reaction (PCR) method for high-throughput production of linear
      templates for yeast CFPS. This procedure allows all functional elements needed
      for Tx/Tl to be added to an open-reading frame directly by overlap extension PCR.
      Our two-step PCR method was successfully applied to three reporter proteins:
      luciferase, green fluorescence protein, and chloramphenicol acetyl transferase,
      yielding 7 to 12.5 MUg mL-1 active protein after 1.5-h batch reactions.
      Surprisingly, the linear templates outperformed plasmid DNA by up to 60%. Hence,
      the presented CFPS method has the potential to rapidly prepare tens to thousands
      of DNA templates without time-consuming cloning work. Further, it holds promise
      for fast and convenient optimization of expression constructs, study of internal
      ribosome entry site, and production of protein libraries for genome-scale
      studies. See accompanying commentary by Russ and Dueber DOI:
      10.1002/biot.201400071. 

PMID- 24677810
TI  - Mother and daughter with a novel phenotype of hand and foot anomalies and severe
      pectus excavatum.

PMID- 24677811
TI  - Simultaneous transapical aortic and mitral valve-in-valve implantation for double
      prostheses dysfunction: case report and technical insights.
AB  - Transcatheter "Valve-in-Valve" implantation (ViV) has shown promising results in
      high-risk patients suffering from structural valve deterioration (SVD) of a
      previously implanted heart valve bioprosthesis. We present a case of a 68-year
      old woman with a history of three previous cardiac operations on the aortic and
      mitral valve. At the time of admission she was severely symptomatic due to a
      simultaneous SVD of a 23 mm aortic and of a 29 mm mitral St. Jude Biocor
      bioprosthesis. Because of the history of several cardiac operations and to her
      comorbidities, the patient was considered with an extremely high surgical risk
      profile and was therefore scheduled for double concomitant mitral and aortic ViV.
      Through a trans-apical approach, the patient underwent 23 and 29 mm Edwards
      Sapien XT implantation in the aortic and mitral bioprosthesis, respectively. The
      procedure was uneventful as well as the following hospital stay. At 6-months
      follow-up the patient is in NYHA class I. Echocardiography shows that the aortic
      bioprosthesis has no leak and the mean gradient is 20 mm Hg while the mitral
      valve has mild leak and maximum and mean gradients are 21 and 10 mm Hg,
      respectively. The three main technical aspects that should be carefully
      considered in double concomitant ViV are: sequence of valve deployment (whether
      to implant the mitral or the aortic valve first), choice of access and valve
      sizing. In conclusion, double simultaneous trans-apical mitral and aortic ViV is
      technically feasible. (c) 2014 Wiley Periodicals, Inc. 

PMID- 24677812
TI  - Biomechanical and antibacterial properties of Tobramycin loaded hydroxyapatite
      coated fixation pins.
AB  - The present study investigates the use of nanoporous, biomimetic hydroxyapatite
      (HA) coatings deposited on TiO2 coated fixation pins as functional implant
      surfaces for the local release of Tobramycin in order to prevent bacterial
      colonization. The impact of HA-coating thickness, coating morphology and
      biomechanical forces during insertion into synthetic bone on the drug loading and
      release properties are analyzed. The coatings are shown to exhibit bactericidal
      effects against Staphylococcus aureus in agar medium for a duration of 6 days
      after loading by adsorption with Tobramycin for only 5 min at elevated
      temperature and pressure. Furthermore, high performance liquid chromatography
      analysis shows a drug release in phosphate buffered saline for 8 days with
      antibiotic concentration remaining above the minimal inhibitory concentration for
      S. aureus during the entire release period. Biomechanical insertion tests into
      synthetic bone and conventional scratch testing demonstrate adhesive strength at
      the HA/TiO2 interface. Biocompatibility is verified by cell viability tests.
      Outgrowth endothelial cells, as well as primary osteoblasts, are viable and
      firmly attached to both HA and TiO2 surfaces. The results presented are
      encouraging and support the concept of functional HA coatings as local drug
      delivery vehicles for biomedical applications to treat as well as to prevent post
      surgical infections.

PMID- 24677813
TI  - Structure-dependent mitochondrial dysfunction and hypoxia induced with single
      walled carbon nanotubes.
AB  - Cytotoxicity of nanomaterials on living systems is known to be affected by their
      size, shape, surface chemistry, and other physicochemical properties. Exposure to
      a well-characterized subpopulation of specific nanomaterials is therefore desired
      to reveal more detailed mechanisms. This study develops scalable density gradient
      ultracentrifugation sorting of highly dispersed single-walled carbon nanotubes
      (SWNTs) into four distinct bands based on diameter, aggregation, and structural
      integrity, with greatly improved efficiency, yield, and reproducibility. With
      guarantee of high yield and stability of four SWNT fractions, it is possible for
      the first time, to investigate the structure-dependent bioeffects of four SWNT
      fractions. it is possible Among these, singly-dispersed integral SWNTs show no
      significant effects on the mitochondrial functions and hypoxia. The aggregated
      integral SWNTs show more significant effects on the mitochondrial dysfunction and
      hypoxia compared to the aggregated SWNTs with poor structure integrity. Then, it
      is found that the aggregated integral SWNTs induced the irregular mitochondria
      respiratory and pro-apoptotic proteins activation, while aggregated SWNTs with
      poor structure integrity greatly enhanced reactive oxygen species (ROS) levels.
      This work supports the view that control of the distinct structure
      characteristics of SWNTs helps establish clearer structure-bioeffect correlation
      and health risk assessment. It is also hoped that these results can help in the
      design of nanomaterials with higher efficiency and accuracy in subcellular
      translocation. 

PMID- 24677815
TI  - Synergy, compatibility, and innovation: merging Lewis acids with stereoselective
      enamine catalysis.
AB  - In recent years there has been an accelerated rate of development in the field of
      organocatalysis, with asymmetric organocatalysis now reaching full maturity. The
      invention of new organocatalytic reactions and the exploration of new concepts
      now appear in tandem with the application of organocatalytic techniques in the
      synthesis of natural products and active pharmaceutical ingredients (APIs). After
      a "golden rush" in organocatalysis, researchers are now starting to combine
      different methods, thereby taking advantage of the significant benefits of
      synergy. Metals are used in combination with organocatalytic processes, thus
      reaching complexity that is found in nature, where enzymes take advantage of the
      presence of certain metals to increase the arsenal of organic transformations
      available. In this Focus review, we illustrate the possibility of a "happy
      marriage" between Lewis acids and organocatalytic stereoselective processes.
      Questions have been raised about the combination of Lewis acids and
      organocatalysis owing to the presence of water and/or strong bases in these
      processes. Some Lewis acids have been shown to be compatible with organocatalysis
      and concepts relating to their use will be illustrated herein. To summarize the
      fruitful use of Lewis acids in stereoselective organocatalytic processes, we will
      draw attention to the advantages and selectivity achieved using this method.

PMID- 24677814
TI  - Characterization of individual mouse cerebrospinal fluid proteomes.
AB  - Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the
      CNS. Characterization of murine CSF proteomes can provide a valuable resource for
      studying CNS injury and disease in animal models. However, the small volume of
      CSF in mice has thus far limited individual mouse proteome characterization.
      Through nonterminal CSF extractions in C57Bl/6 mice and high-resolution 2D-LC
      MS/MS analysis of individual murine samples, we report the most comprehensive
      proteome characterization of individual murine CSF to date. We identified a total
      of 566 unique proteins, including 128 proteins from three individual CSF samples
      that have been previously identified in brain tissue. Our methods and analysis
      provide a mechanism for individual murine CSF proteome analysis. The data are
      available in the ProteomeXchange with identifier PXD000248
      (http://proteomecentral.proteomexchange.org/dataset/PXD000248). 

PMID- 24677816
TI  - Abstracts from the 2014 Pediatric Rheumatology Symposium, April 3-6, 2014,
      Orlando, FL.

PMID- 24677884
TI  - A130: Is the CCR5-delta32 Mutation Protective Against Systemic-Onset Juvenile
      Idiopathic Arthritis?
AB  - BACKGROUND/PURPOSE: The CCR5 protein is a chemokine receptor, and is known to be
      expressed on T cells, macrophages, dendritic and microglia cells. It is believed
      that different prevalence of HLA and CCR5- delta32-a 32 base pair deletion in the
      coding region-in various ethnic groups is associated with the severity and
      prevalence of chemokine-mediated autoimmune diseases, systemic-onset Juvenile
      Idiopathic Arthritis (soJIA) being among them (Del Rincon et al., 2003). Since
      the end of the last century the protective role of the CCR5-delta32 mutation
      against JIA is discussed (Hinks et al., 2010), though it seems the role of this
      mutation is less simple than was hitherto thought. The purposes of the study was
      to compare the prevalence of the CCR5-delta32 mutation in children with and
      without soJIA, to assess the association of this mutation with the severity of
      the disease and thus to evaluate its protective role. METHODS: 234 children (193
      of European origin, 25-Hispanic or Latino, 14-Afro-Americans, 3-of Asian origin)
      with soJIA living in the USA and in the Northwestern part of Russia were enrolled
      in the study. Genomic DNA was isolated from blood samples using QIAamp Mini Kit
      and amplified by PCR. The following oligonucleotide primers were used to detect
      CCR5 d32: CCR5- Delta32-F: 5'CTTCATTACACCTGCAGTC3', CCR5-Delta32-R:
      5'TGAAGATAAGCCTCACAGCC3' by following condition: 95 degrees -5'*1; 95 degrees 
      15"->55 degrees -15"->72 degrees -60"*40; 72 degrees -10'*3->4 degrees -infinity;
      the resulting PCR products were separated on 2% agarose gel by electrophoresis
      and visualized by Gel Doc XR Plus. RESULTS: Mutation was revealed only in
      children of European origin. Though the prevalence of the heterozygous CCR5
      delta32 mutation being 16% and 21% in the USA and in Russia correspondingly
      didn't excel from its prevalence in populations in total (10-18% for Northwestern
      Russia, Kofiady, 2008; 11,8%- for white American group, Downer et al, 2002), some
      laboratory and clinical signs of soJIA proved to be related to the mutation (see
      ). Heterozygous CCR5-delta32 genotype was associated with milder so-JIA course
      and predominance of the articular features over systemic. [Table: see text]
      CONCLUSION: The results of the study may be considered rather not supporting the
      idea of the protective role of the CCR5-delta32 mutation against soJIA, though
      the revealed associations-most of them related to the signs of the Macrophage
      Associated Syndrome-can be the basis for a more sophisticated research.

PMID- 24678000
TI  - Focus on technology: How important is resolution in telecytopathology?
AB  - BACKGROUND: The authors conducted an analysis of 2 telepathology systems with
      different resolutions to determine how resolution affects the pathologists'
      ability to provide preliminary diagnoses for fine-needle aspirations (FNA).
      METHODS: FNA cases evaluated by telepathology between February 1, 2011 and
      January 18, 2012 were reviewed. Concordance indices between preliminary and final
      diagnoses were calculated for cases assessed with two proprietary systems (the
      Remote Meeting Technologies iMedHD system and the Olympus NetCam system) using 3
      diagnostic classifications (negative, atypical, and suspicious/positive). A
      Wilcoxon rank-sum test was used to compare the number of passes necessary to
      determine adequacy. RESULTS: In total, 298 NetCam cases and 26 iMedHD cases were
      evaluated. The concordance index, which was calculated using the 3
      classifications, was 0.943 (95% confidence interval, 0.922-0.963) for NetCam
      compared with 0.951 (95% confidence interval, 0.898-1.000) for iMedHD. The mean
      value for the number of passes required to determine adequacy was 2.2 for NetCam
      and 2.1 for iMedHD (P = .838). CONCLUSIONS: The results from statistical analyses
      demonstrated no difference in the concordance indices between preliminary and
      final diagnoses or in the number of passes necessary to render adequacy between
      the 2 telepathology systems. However, because it had higher resolution along with
      other features, the iMedHD system achieved greater user satisfaction.

PMID- 24678001
TI  - Iron oxide nanoparticles embedded in activated carbons prepared from
      hydrothermally treated waste biomass.
AB  - Particles of iron oxide (Fe3O4 ; 20-40 nm) were embedded within activated carbons
      during the activation of hydrothermally carbonized (HTC) biomasses in a flow of
      CO2. Four different HTC biomass samples (horse manure, grass cuttings, beer
      production waste, and biosludge) were used as precursors for the activated
      carbons. Nanoparticles of iron oxide formed from iron catalyst included in the
      HTC biomasses. After systematic optimization, the activated carbons had specific
      surface areas of about 800 m2g1. The pore size distributions of the activated
      carbons depended strongly on the degree of carbonization of the precursors.
      Activated carbons prepared from highly carbonized precursors had mainly
      micropores, whereas those prepared from less carbonized precursors contained
      mainly mesopores. Given the strong magnetism of the activated carbon-nano-Fe3O4
      composites, they could be particularly useful for water purification.

PMID- 24678002
TI  - Engineering of a bispecific affibody molecule towards HER2 and HER3 by addition
      of an albumin-binding domain allows for affinity purification and in vivo half
      life extension.
AB  - Emerging strategies in cancer biotherapy include the generation and application
      of bispecific antibodies, targeting two tumor-associated antigens for improved
      tumor selectivity and potency. Here, an alternative format for bispecific
      molecules was designed and investigated, in which two Affibody molecules were
      linked by an albumin-binding domain (ABD). Affibody molecules are small (6 kDa)
      affinity proteins and this new format allows for engineering of molecules with
      similar function as full-length bispecific antibodies, but in a dramatically
      smaller size (around eight-fold smaller). The ABD was intended to function both
      as a tag for affinity purification as well as for in vivo half-life extension in
      future preclinical and clinical investigations. Affinity-purified bispecific
      Affibody molecules, targeting HER2 and HER3, showed simultaneous binding to the
      three target proteins (HER2, HER3, and albumin) when investigated in biosensor
      assays. Moreover, simultaneous interactions with the receptors and albumin were
      demonstrated using flow cytometry on cancer cells. The bispecific Affibody
      molecules were also able to block ligand-induced phosphorylation of the HER
      receptors, indicating an anti-proliferative effect. We believe that this compact
      and flexible format has great potential for developing new potent bispecific
      affinity proteins in the future, as it combines the benefits of a small size
      (e.g. improved tissue penetration and reduced cost of goods) with a long
      circulatory half-life. 

PMID- 24678003
TI  - Haploinsufficiency of MEIS2 is associated with orofacial clefting and learning
      disability.
AB  - MEIS2 is a homeodomain-containing transcription factor of the TALE superfamily
      that has been proven important for development. We confirm and extend a recent
      single clinical report stating that deletions in MEIS2 can cause cleft palate
      [Crowley et al. (2010); Am J Med Genet 152A:1326-1327]. Here we report on five
      additional patients with 15q14 deletions of sizes 0.6, 0.6, 1.0, 1.9, and 4.8 Mb,
      respectively, all involving MEIS2. In addition, we present a family with four
      affected individuals and an intragenic 58 kb direct duplication disrupting MEIS2.
      In total, 7/9 cases had clefting, from mild (submucous cleft palate) to severe
      (cleft lip and palate), and 3/9 cases had ventricular septal defects. All cases
      had delayed motor development and most had learning disability, at worst in the
      mild intellectual disability range. The cases had overlapping facial features
      (broad forehead, finely arched eyebrows, mildly shortened philtrum, and tented
      upper lip) but individually they were not considered to be dysmorphic. Our
      results show that MEIS2 is a gene needed for palate closure. In syndromic cases
      of cleft palate, MEIS2 should be considered among the candidate genes, for
      example, in cases without 22q11.2 deletions.

PMID- 24678004
TI  - In vivo telemetric determination of shear and axial loads on a regenerative
      cartilage scaffold following ligament disruption.
AB  - Recent interest in repair of chondral and osteochondral cartilage defects to
      prevent osteoarthritis caused by ligament disruption has led to the research and
      development of biomimetic scaffolds combined with cell-based regeneration
      techniques. Current clinical focal defect repair strategies have had limited
      success. New scaffold-based approaches may provide solutions that can repair
      extensive damage and prevent osteoarthritis. This study utilized a novel scaffold
      design that accommodated strain gauges for shear and axial load monitoring in the
      canine stifle joint through implantable telemetry technology. Loading changes
      induced by ligament disruption are widely implicated in the development of injury
      related osteoarthritis. Seeding the scaffold end with progenitor cells resulted
      in higher shear stress than without cell seeding and histology showed
      significantly more bone and cartilage formation. Biomechanically, the effect of
      transecting the anterior cruciate ligament was a significant reduction in braking
      load in shear, but no change axially, and conversely a significant reduction in
      push-off load axially, but no change in shear. This is the first study to report
      shear loads measured directly in knee joint tissue. Further, advances of these
      measurement techniques are critical to developing improved regeneration
      strategies and personalizing reliable rehabilitation protocols.

PMID- 24678005
TI  - Severe muscle depletion predicts postoperative length of stay but is not
      associated with survival after liver transplantation.
AB  - Muscle depletion or sarcopenia is associated with increased mortality in patients
      with cirrhosis; how it affects mortality after liver transplantation requires
      further study. In this study, we aimed to establish whether sarcopenia predicts
      increased morbidity or mortality after liver transplantation. We analyzed 248
      patients with cirrhosis who had a computed tomography (CT) scan including the
      third lumbar vertebra before liver transplantation. Data were recovered from
      medical charts, the skeletal muscle cross-sectional area was measured with CT,
      and sarcopenia was defined with previously published sex- and body mass index
      specific cutoffs. One hundred sixty-nine patients (68%) were male, and the mean
      age at transplantation was 55 +/- 1 years. The etiologies of cirrhosis were
      hepatitis C virus (51%), alcohol (19%), autoimmune liver diseases (15%),
      hepatitis B virus (8%), and other etiologies (7%). Sarcopenia was present in 112
      patients (45%), and it was more frequent in males (P = 0.002), patients with
      ascites (P = 0.02), and patients with higher bilirubin levels (P = 0.05),
      creatinine levels (P = 0.02), international normalized ratios (P = 0.04), Child
      Pugh scores (P = 0.002), and Model for End-Stage Liver Disease scores (P =
      0.002). The median survival period after liver transplantation was 117 +/- 17
      months for sarcopenic patients and 146 +/- 20 months for nonsarcopenic patients
      (P = 0.4). Sarcopenic patients had longer hospital stays (40 +/- 4 versus 25 +/-
      3 days; P = 0.005) and a higher frequency of bacterial infections within the
      first 90 days after liver transplantation (26% versus 15%, P = 0.04) in
      comparison with nonsarcopenic patients. In conclusion, sarcopenia is one of the
      most common complications in patients with cirrhosis and is predictive of longer
      hospital stays and a higher risk of perioperative bacterial infections after
      liver transplantation, but it is not associated with increased mortality.

PMID- 24678006
TI  - Influence of microvascular resistance on fractional flow reserve after successful
      percutaneous coronary intervention.
AB  - OBJECTIVES AND BACKGROUND: Increased microvascular resistance may impair
      hyperemic coronary flow by limiting the maximal and constant vasodilation,
      resulting in increased fractional flow reserve (FFR) due to the underestimation
      of the translesional pressure gradient. We examined whether microvascular
      resistance affects FFR after successful percutaneous coronary intervention (PCI).
      METHODS AND RESULTS: We measured FFR and the index of microcirculatory resistance
      (IMR) in 104 coronary arteries of 98 patients after successful elective stenting.
      FFR values were compared according to the quartiles of the IMR values. Coronary
      flow was assessed using the hyperemic mean transit time (Tmn ). The IMR values
      for the interquartile ranges of 8.5-11.3, 13.9-16.3, 20.9-24.5, and 34.2-61.6
      were 10.2, 15.1, 22.8, and 38.2, respectively. Both FFR and Tmn values differed
      significantly across the IMR quartiles (P < 0.001). The angiographic and
      intravascular ultrasound findings and post-PCI cardiac troponin levels showed no
      significant difference across the IMR quartiles. Multivariate logistic regression
      analysis revealed that the left anterior descending artery lesion location (odds
      ratio [OR] 0.17, 95% confidence interval [CI] 0.06-0.49, P = 0.001), IMR (OR
      1.05, 95% CI 1.01-1.09, P = 0.012), and minimal cross-sectional lumen area (OR
      1.49, 95% CI 1.03-2.17, P = 0.036) were independent predictors of increased FFR.
      CONCLUSIONS: Increased microvascular resistance may reduce coronary flow and
      increase FFR after successful elective PCI.

PMID- 24678007
TI  - Solvothermal-induced self-assembly of Fe2O3/GS aerogels for high Li-storage and
      excellent stability.
AB  - A novel solvothermal-induced self-assembly approach, using colloid sol as
      precursor, is developed to construct monolithic 3D metal oxide/GS (graphene
      sheets) aerogels. During the solvothermal process, graphene oxide (GO) is highly
      reduced to GS and self-assembles into 3D macroscopic hydrogels, accompanying with
      in situ transformation of colloid sol to metal oxides. As a proof of concept, Fe2
      O3 /GS aerogels are synthesized based on Fe(OH)3 sol, in which GS self-assemble
      into an interconnected macroporous framework and Fe2 O3 nanocrystals (20-50 nm)
      uniformly deposit on GS. Benefitting from the integration of macroporous
      structures, large surface area, high electrical conductivity, and good electrode
      homogeneity, the hybrid electrode manifests a superior rate capability (930, 660
      and 520 mAh g(-1) at 500, 2000 and 4000 mA g(-1), respectively) and excellent
      prolonged cycling stability at high rates (733 mAh g(-1) during 1000
      charge/discharge cycles at 2000 mA g(-1)), demonstrating its great potential for
      application in high performance lithium ion batteries. The work described here
      provides a versatile pathway to construct various graphene-based hybrid aerogels.

PMID- 24678008
TI  - Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging
      mass spectrometry.
AB  - Cholangiocarcinoma (CC) is the second most common primary malignancy of the
      liver. Although all CC derive from biliary epithelial cells, two main subtypes,
      hilar (H), and peripheral (P) CC are described. The objective of the study was to
      compare, using MALDI imaging mass spectrometry (MALDI IMS), in situ proteomic
      profiles of H- and P-CC in order to assess whether these subtypes may express
      different markers and to describe their respective localizations. Twenty-seven CC
      (16 P-CC and 11 H-CC) were subjected to MALDI IMS. Proteomic data were submitted
      to a dedicated cross-classification comparative design, enabling comparison of
      the entire generated spectra. Immunohistochemistry was performed for validation.
      Comparative analysis yielded a list of 19 differential protein peaks for the two
      subtypes, 14 of which were overexpressed in H-CC and five in P-CC. Among H-CC
      protein markers, most discriminant were human neutrophil peptides 1-3 that were
      expressed mainly by tumor cells and S100 proteins (A6 and A11) that were
      restricted to the stromal area. In P-CC, thymosin beta4 was diffusely
      overexpressed. These results highlight the potential of MALDI IMS to discover new
      relevant biomarkers of CC and to characterize the heterogeneity of the two
      different subtypes. 

PMID- 24678009
TI  - Phosphine-initiated domino reaction: a convenient method for the preparation of
      spirocyclopentanones.
AB  - An efficient synthetic approach has been developed for the construction of the
      spirocyclopentanone skeleton via a phosphine-catalyzed [3+2] annulation reaction.
      With this novel and economical protocol, various quaternary carbon-centered
      spirocyclopentanones could be readily obtained. 

PMID- 24678010
TI  - Cell morphology in injectable nanostructured biosynthetic hydrogels.
AB  - Even though inducing structural features on the nanometric scale has been shown
      to be a powerful tool in tissue engineering, almost all nanostructuring
      techniques available today cannot be applied to injectable hydrogel scaffolds.
      The current research explores such a novel technique and its effect on scaffold's
      properties, cell morphology, and cell-material interaction. Nanostructuring is
      achieved by covalently binding Pluronic((r)) F127 molecules to biosynthetic
      hydrogels. Analysis of cell morphology revealed spindled cell morphologies at day
      4 in culture. The bound Pluronic((r)) F127 diminished the swelling ability and
      enhanced the Young modulus, thus indicating that the bound molecules crosslink
      the hydrogel. The relation between matrix characteristics and cell morphology was
      analyzed and the importance of nanostructuring was demonstrated.

PMID- 24678011
TI  - Fine-needle aspiration cytology of Merkel cell carcinoma-a review of 69 cases.
AB  - This study reviewed the clinical presentation, cytologic findings, and the
      immunophenotype of 69 Merkel cell carcinoma (MCC) cases sampled by fine-needle
      aspiration (FNA).  Demographic and clinical data, the cytology findings, and
      results of ancillary testing were reviewed.  Median patient age was 78 years (37
      104) with a 1:1.8 female to male ratio. The most common FNA sites sampled
      included lymph nodes in the neck, the axillary region, the inguinal region and
      the parotid gland. Most patients had a history of MCC (68%) and/or non-MCC
      malignancy (70%).  The common cytologic pattern was a cellular smear with
      malignant cells arranged in a dispersed pattern with variable numbers of
      disorganized groups of cells. Cytoplasm was scant or absent and nuclei showed
      mild to moderate anisokaryosis, stippled chromatin, inconspicuous nucleoli, and
      nuclear molding. Numerous apoptotic bodies were often present.  Cell block
      samples (28 cases) were usually positive for cytokeratins in a perinuclear dot
      pattern, including 88% of cases with CK20 positivity. CD56 was the most sensitive
      (95%) neuroendocrine marker on cell blocks and was also positive with flow
      cytometry in nine cases tested.  MCC is most commonly seen in FNA specimens from
      the head and neck of elderly patients, often with a history of previous skin
      lesions. Occasional cases present in younger patients and some may be mistaken
      for other round blue cell tumors, such as lymphoma. CD 56 may be a useful marker
      in cell block preparations and in flow cytometric analysis of MCC.

PMID- 24678012
TI  - Ultrasounds in melted poly(ethylene glycol) promote copper-catalyzed cyanation of
      aryl halides with K(4)[Fe(CN)(6)].
AB  - Melted poly(ethylene glycols) (PEGs) were used for the first time as solvent for
      the sonochemically promoted cyanation of aryl halides employing inexpensive and
      safe K4[Fe(CN)6] and a relatively low amount of Cu-based catalyst. The Mw (weight
      average polymer molecular weight) of PEG proved to notably influence the
      substrate conversion, which is indicative of a strong dependence of the
      sonication efficacy on solvent properties. Gel permeation chromatography (GPC), X
      ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM)
      contributed to the characterization of the polymer and the elucidation of the
      catalytic system.

PMID- 24678013
TI  - Opportunities for cytotechnologists in a changing environment.

PMID- 24678014
TI  - A beta-lactone-based antivirulence drug ameliorates Staphylococcus aureus skin
      infections in mice.
AB  - Skin infections caused by Staphylococcus aureus are a major clinical concern,
      especially if they are caused by multi-resistant strains. In these cases, a
      spread into deeper soft tissues or the bloodstream results in life-threatening
      conditions that are difficult to treat by conventional antibiotics. Previous in
      vitro experiments with a small beta-lactone-based molecule demonstrated that
      antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in
      their virulence and corresponding pathogenicity. In this work, in vivo mouse
      studies show that this methodology is effective for the treatment of skin
      abscesses in mice. A single dose of the beta-lactone significantly decreased
      abscess size even when applied 6 h post-infection. Although the molecule requires
      pharmacological optimization (improved stability, for example), this study
      emphasizes the potential value of antivirulence therapies.

PMID- 24678015
TI  - Future developments in XLHED treatment approaches.
AB  - X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common genetic
      disorder of ectoderm development, presenting with abnormalities of skin, teeth,
      hair, and secretory glands. In the first years of life, XLHED-affected patients
      are at risk for life-threatening hyperthermia and pulmonary infection. Survival
      into childhood and beyond is associated with severe dental abnormalities as well
      as chronic growth, respiratory, skin, eye, and psychosocial disorders. Currently
      there are no approved therapies to restore function in disorders of development
      like XLHED. Over the last two decades, molecular research has provided convincing
      evidence that alterations in the ectodysplasin (EDA) gene that disrupt the
      encoded protein EDA-A1 are causative for XLHED. In mouse and dog XLHED models,
      administration of a single course of an EDA-A1 replacement protein (EDI200)
      resulted in permanent correction of the key phenotypic features, providing the
      first hope for an effective, targeted therapy. Animal models for genetic
      disorders have their strengths and limitations that must be considered when
      modeling clinical studies in human patients. Of greatest significance in the case
      of a developmental disorder may be the relative timeline for normal development
      and the maturation level at birth. With FDA clearance to start EDI200 studies in
      XLHED patients, we are on the verge of converting a decade of animal studies into
      the first test of a novel paradigm for rescue and permanent correction of a human
      developmental disorder.

PMID- 24678016
TI  - Nano/microfibrous polymeric constructs loaded with bioactive agents and designed
      for tissue engineering applications: a review.
AB  - Nano/microfibrous polymeric constructs present various inherent advantages, such
      as highly porous architecture and high surface to volume ratio, making them
      attractive for tissue engineering purposes. Electrospinning is the most preferred
      technique for the fabrication of polymeric nanofibrous assemblies that can mimic
      the physical functions of native extracellular matrix greatly favoring cells
      attachment and thus influencing their morphology and activities. Different
      approaches have been developed to apply polymeric microfiber fabrication
      techniques (e.g. wet-spinning) for the obtainment of scaffolds with a three
      dimensional network of micropores suitable for effective cells migration.
      Progress in additive manufacturing technology has led to the development of
      complex scaffold's shapes and microfibrous structures with a high degree of
      automation, good accuracy and reproducibility. Various loading methods, such as
      direct blending, coaxial electrospinning and microparticles incorporation, are
      enabling to develop customized strategies for the biofunctionalization of
      nano/microfibrous scaffolds with a tailored kinetics of release of different
      bioactive agents, ranging from small molecules, such as antibiotics, to protein
      drugs, such as growth factors, and even cells. Recent activities on the
      combination of different processing techniques and loading methods for the
      obtainment of biofunctionalized polymeric constructs with a complex multiscale
      structure open new possibilities for the development of biomimetic scaffolds
      endowed with a hierarchical architecture and a sophisticated release kinetics of
      different bioactive agents. This review is aimed at summarizing current advances
      in technologies and methods for manufacturing nano/microfibrous polymeric
      constructs suitable as tissue engineering scaffolds, and for their combination
      with different bioactive agents to promote tissue regeneration and therapeutic
      effects.

PMID- 24678017
TI  - Donor-specific alloantibodies are associated with fibrosis progression after
      liver transplantation in hepatitis C virus-infected patients.
AB  - Hepatitis C virus (HCV) fibrosis progression after liver transplantation (LT) is
      accelerated in comparison with fibrosis progression before transplantation. The
      vast majority of the risk factors for fibrosis progression after LT are not
      modifiable. With the goal of identifying modifiable risk factors for fibrosis
      progression, we evaluated the impact of preformed and de novo donor-specific
      human leukocyte antigen alloantibodies (DSAs) on fibrosis progression after LT in
      HCV-viremic patients. After blinding, we analyzed all 507 HCV-viremic patients
      who underwent primary LT from January 2000 to May 2009 and had pretransplant and
      posttransplant samples available for analysis (86% of the total) for preformed
      and de novo class I and class II DSAs with a mean fluorescence intensity >= 5000
      with single-antigen bead technology. Fibrosis was assessed on the basis of
      indication and protocol liver biopsies; compliance with protocol liver biopsies
      at 1, 2, and 5 years was >=80%. Preformed class I DSAs [hazard ratio (HR) = 1.44,
      P = 0.04] and class II DSAs (HR = 1.86, P < 0.001) were independent predictors of
      progression to stage 2-4 fibrosis, and de novo DSAs (HR = 1.41, P = 0.07) had
      borderline significance. In addition, preformed class I DSAs (HR = 1.63, P =
      0.03) and class II DSAs (HR = 1.72, P = 0.03) were statistically significantly
      associated with an increased risk of death. In conclusion, after we controlled
      for donor and recipient characteristics in multivariate modeling, DSAs were
      independently associated with fibrosis progression and death after LT in HCV
      viremic patients.

PMID- 24678018
TI  - Proteoform analysis of lipocalin-type prostaglandin D-synthase from human
      cerebrospinal fluid by isoelectric focusing and superficially porous liquid
      chromatography with Fourier transform mass spectrometry.
AB  - Lipocalin-type prostaglandin D-synthase (L-PGDS) in cerebrospinal fluid
      contributes to the maturation and maintenance of the CNS. L-PGDS PTMs may
      contribute to pathobiology of different CNS diseases, but methods to monitor its
      proteoforms are limited. Herein, we combined off-gel IEF and superficially porous
      LC (SPLC) with Fourier transform MS to characterize common cerebrospinal fluid L
      PGDS proteoforms. Across 3D physiochemical space (pI, hydrophobicity, and mass),
      217 putative proteoforms were observed from 21 to 24 kDa and pI 5-10.
      Glycoprotein accurate mass information, combined with MS/MS analysis of peptides
      generated from 2D-fractionated proteoforms, enabled the putative assignment of
      208 proteoforms with varied PTM positional occupants. Fifteen structurally
      related N-glycans at N29 and N56 were observed, with different N-glycan
      compositional variants being preferred on each amino acid. We also observed that
      sialic acid content was a major factor for pI shifts between L-PGDS proteoforms.
      Other putative PTMs characterized include a core-1 HexHexNAc-O-glycan at S7,
      acetylation at K16 and K138, sulfonation at S41 and T142, and dioxidation at C43
      and C145. The IEF-SPLC-MS platform presented provides 30-40* improved peak
      capacity versus conventional 2DE and shows potential for repeatable proteoform
      analysis of surrogate PTM-based biomarkers. 

PMID- 24678019
TI  - Configurable low-cost plotter device for fabrication of multi-color sub-cellular
      scale microarrays.
AB  - The construction and operation of a low-cost plotter for fabrication of
      microarrays for multiplexed single-cell analyses is reported. The printing head
      consists of polymeric pyramidal pens mounted on a rotation stage installed on an
      aluminium frame. This construction enables printing of microarrays onto glass
      substrates mounted on a tilt stage, controlled by a Lab-View operated user
      interface. The plotter can be assembled by typical academic workshops from
      components of less than 15,000 Euro. The functionality of the instrument is
      demonstrated by printing DNA microarrays on the area of 0.5 cm2 using up to three
      different oligonucleotides. Typical feature sizes are 5 MUm diameter with a pitch
      of 15 MUm, leading to densities of up to 10(4)-10(5) spots/mm2. The fabricated
      DNA microarrays are used to produce sub-cellular scale arrays of bioactive
      epidermal growth factor peptides by means of DNA-directed immobilization. The
      suitability of these biochips for cell biological studies is demonstrated by
      specific recruitment, concentration, and activation of EGF receptors within the
      plasma membrane of adherent living cells. This work illustrates that the
      presented plotter gives access to bio-functionalized arrays usable for
      fundamental research in cell biology, such as the manipulation of signal pathways
      in living cells at subcellular resolution.

PMID- 24678020
TI  - Remote impacts of methyl substituents on the guest-binding ability of self
      assembled cages.
AB  - We synthesized self-assembled coordination cages in which 1,10-phenanthroline
      derivatives serve as capping ligands. Substituents at the 2,9-positions of the
      phenanthroline ligand covered the outside of the cage but had an impact on the
      guest binding inside the cage. Introduction of methyl groups at the 2,9-positions
      allowed the cage to accommodate tetraphenylsilane. Bulky mesityl groups
      overhanging the cage framework significantly shrunk the cage cavity through pi-pi
      interactions with the aromatic panels of the cage. The p-methyl group of the
      mesityl substituent was a determinant of the restricted motion of 4,4'
      dimethoxybenzil inside the cage at high temperature. Thus, the presence or
      absence of one methyl group, which is far from the guest-binding site, makes a
      significant difference in the guest species and motions inside the cage. 

PMID- 24678021
TI  - Shrinking mechanism of a porous collagen matrix immersed in solution.
AB  - The porous structure of collagen-based matrices enables the infiltration of cells
      both in in vitro and clinical applications. Reconstituted porous collagen
      matrices often collapse when they are in contact with aqueous solutions; however,
      the mechanism for the collapse of the pores is not understood. We, therefore,
      investigated the interactions between the collagen matrix and different
      solutions, and discuss the mechanisms for the change in microstructure of the
      matrix on immersing it in solution. When a dried collagen matrix was immersed in
      aqueous solutions, the matrix shrunk and pores close to the surface closed. The
      shrinkage ratio and thickness of the compact microstructure close to the
      superficial area decreased with increasing ethanol content in the solution. The
      original porous structure of the collagen matrix was preserved when the matrix
      was immersed in absolute ethanol. The shrinkage of a porous collagen matrix in
      contact with aqueous solutions was attributed to the liquid/gas interfacial
      tension. The average pore diameter of the matrix also significantly affected the
      shrinkage of the matrix. The shrinkage of the matrix, explained using the Young
      Laplace equation, was found to result from the pressure drop, and especially in
      the pores located superficially, leading to the collapse of the matrix
      microstructure. The integrity of the porous microstructure allows better
      penetration of cells in medical applications. The numbers of NIH/3T3 fibroblasts
      penetrated through the hydrated Col/PBS porous collagen matrices pre-immersed in
      absolute ethanol with subsequent water and DMEM culture medium replacements were
      significantly higher than those through matrices hydrated directly in DMEM.

PMID- 24678023
TI  - Fast Pyrolysis of Wood for Biofuels: Spatiotemporally Resolved Diffuse
      Reflectance In situ Spectroscopy of Particles.
AB  - Fast pyrolysis of woody biomass is a promising process capable of producing
      renewable transportation fuels to replace gasoline, diesel, and chemicals
      currently derived from nonrenewable sources. However, biomass pyrolysis is not
      yet economically viable and requires significant optimization before it can
      contribute to the existing oil-based transportation system. One method of
      optimization uses detailed kinetic models for predicting the products of biomass
      fast pyrolysis, which serve as the basis for the design of pyrolysis reactors
      capable of producing the highest value products. The goal of this work is to
      improve upon current pyrolysis models, usually derived from experiments with low
      heating rates and temperatures, by developing models that account for both
      transport and pyrolysis decomposition kinetics at high heating rates and high
      temperatures (>400  degrees C). A new experimental technique is proposed herein:
      spatiotemporally resolved diffuse reflectance in situ spectroscopy of particles
      (STR-DRiSP), which is capable of measuring biomass composition during fast
      pyrolysis with high spatial (10 MUm) and temporal (1 ms) resolution.
      Compositional data were compared with a comprehensive 2D single-particle model,
      which incorporated a multistep, semiglobal reaction mechanism, prescribed
      particle shrinkage, and thermophysical properties that varied with temperature,
      composition, and orientation. The STR-DRiSP technique can be used to determine
      the transport-limited kinetic parameters of biomass decomposition for a wide
      variety of biomass feedstocks.

PMID- 24678022
TI  - Putting an eye on cytological specimens: an audit of the clinical impact of
      thyroid fine-needle aspiration in different health care settings.
AB  - There is published evidence showing less cost-benefit approaches in the
      evaluation of thyroid nodules. We performed an institutional audit of the
      cytologic diagnosis of thyroid fine-needle aspiration (FNA) in an attempt to
      perceive the clinical impact of this technique on the management of thyroid
      nodules and to compare it in two different types of health care: Primary Care
      Medicine and Endocrinology. We performed a retrospective analysis to the
      electronic records of patients referred from General Practitioners (GP) and
      Endocrinologists (E) for thyroid FNA between 2010 and 2012. Request forms for
      cytological reports where retrieved for analysis of clinical and cytological
      data. The database search retrieved 1655 patients (female gender: 88.2%; GP
      references: 51.8%). Preprocedure clinical information was available from 157 out
      of 2005 nodules (7.8%). Significant differences in cytological diagnosis were
      seen in "Nondiagnostic" (GP: 11.6%; E: 7.5%, chi(2)  = 0.002) and "Benign"
      categories (GP: 75%; E: 81.8%, chi(2)  < 0.001). The main potential cause of
      "Nondiagnostic" samples was nodules smaller than one centimeter (total: 14 cases;
      GP: 7; E: 7). Reasons to request FNA for these nodules were provided in 6 out of
      27 cases (GP: 0/16; E: 6/11, P < 0.001). The rate of insufficient samples was
      inversely correlated with nodule size (tau = -0.242, P = 0.001). When evaluating
      thyroid nodules, clinicians should take into account the limitations of FNA, the
      international recommendations for better cost-benefit approaches and the
      importance of a well-informed cytopathologist for better cytological diagnostic
      results.

PMID- 24678025
TI  - The cranial nerve skywalk: A 3D tutorial of cranial nerves in a virtual platform.
AB  - Visualization of the complex courses of the cranial nerves by students in the
      health-related professions is challenging through either diagrams in books or
      plastic models in the gross laboratory. Furthermore, dissection of the cranial
      nerves in the gross laboratory is an extremely meticulous task. Teaching and
      learning the cranial nerve pathways is difficult using two-dimensional (2D)
      illustrations alone. Three-dimensional (3D) models aid the teacher in describing
      intricate and complex anatomical structures and help students visualize them. The
      study of the cranial nerves can be supplemented with 3D, which permits the
      students to fully visualize their distribution within the craniofacial complex.
      This article describes the construction and usage of a virtual anatomy platform
      in Second LifeTM, which contains 3D models of the cranial nerves III, V, VII, and
      IX. The Cranial Nerve Skywalk features select cranial nerves and the associated
      autonomic pathways in an immersive online environment. This teaching supplement
      was introduced to groups of pre-healthcare professional students in gross anatomy
      courses at both institutions and student feedback is included.

PMID- 24678024
TI  - Design, synthesis and biological evaluation of 4-amino-N- (4
      aminophenyl)benzamide analogues of quinoline-based SGI-1027 as inhibitors of DNA
      methylation.
AB  - Quinoline derivative SGI-1027 (N-(4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl)
      4-(quinolin-4-ylamino)benzamide) was first described in 2009 as a potent
      inhibitor of DNA methyltransferase (DNMT) 1, 3A and 3B. Based on molecular
      modeling studies, performed using the crystal structure of Haemophilus
      haemolyticus cytosine-5 DNA methyltransferase (MHhaI C5 DNMT), which suggested
      that the quinoline and the aminopyridimine moieties of SGI-1027 are important for
      interaction with the substrates and protein, we designed and synthesized 25
      derivatives. Among them, four compounds-namely the derivatives 12, 16, 31 and 32
      exhibited activities comparable to that of the parent compound. Further
      evaluation revealed that these compounds were more potent against human DNMT3A
      than against human DNMT1 and induced the re-expression of a reporter gene,
      controlled by a methylated cytomegalovirus (CMV) promoter, in leukemia KG-1
      cells. These compounds possessed cytotoxicity against leukemia KG-1 cells in the
      micromolar range, comparable with the cytotoxicity of the reference compound, SGI
      1027. Structure-activity relationships were elucidated from the results. First,
      the presence of a methylene or carbonyl group to conjugate the quinoline moiety
      decreased the activity. Second, the size and nature of the aromatic or
      heterocycle subsitutents effects inhibition activity: tricyclic moieties, such as
      acridine, were found to decrease activity, while bicyclic substituents, such as
      quinoline, were well tolerated. The best combination was found to be a bicyclic
      substituent on one side of the compound, and a one-ring moiety on the other side.
      Finally, the orientation of the central amide bond was found to have little
      effect on the biological activity. This study provides new insights in to the
      structure-activity relationships of SGI-1027 and its derivative.

PMID- 24678026
TI  - Biomineralization regulation by nano-sized features in silk fibroin proteins:
      synthesis of water-dispersible nano-hydroxyapatite.
AB  - In the present study, silk fibroin (SF) was used as a template to prepare nano
      hydroxyapatite (nano-HA) via a biomineralization process. We observed that the
      content of SF affected both the morphology and water dispersibility of nano-HA
      particles. Scanning electron microscope (SEM), transmission electron microscopy
      (TEM), X-ray diffraction (XRD), zetasizer, and Fourier transform infrared
      spectroscopy (FTIR) were used to examine nano-HA particle features including the
      surface morphology, aggregation performance, and crystallization. Rod-like nano
      HA particles with desired water dispersibility were achieved when the ratio of
      SF/HA (calculated) was above 7:3. SEM, TEM, and zeta potential results revealed
      that nano-HA particles were enclosed by the SF which formed a negative charge
      layer preventing the aggregation of HA nanoparticles in aqueous solution.
      Moreover, the nano-HA particles were able to re-disperse in water without
      precipitation for two weeks at room temperature, 60 degrees C, and 90 degrees C.
      Our work suggested a facile and effective approach of designing water-dispersible
      nano-HA particles which may have wide potential application in tissue engineering
      especially bone regeneration.

PMID- 24678027
TI  - Suspension trapping (STrap) sample preparation method for bottom-up proteomics
      analysis.
AB  - Despite recent developments in bottom-up proteomics, the need still exists in a
      fast, uncomplicated, and robust method for comprehensive sample processing
      especially when applied to low protein amounts. The suspension trapping method
      combines the advantage of efficient SDS-based protein extraction with rapid
      detergent removal, reactor-type protein digestion, and peptide cleanup. Proteins
      are solubilized in SDS. The sample is acidified and introduced into the
      suspension trapping tip incorporating the depth filter and hydrophobic
      compartments, filled with the neutral pH methanolic solution. The instantly
      formed fine protein suspension is trapped in the depth filter stack-this crucial
      step is aimed at separating the particulate matter in space. SDS and other
      contaminants are removed in the flow-through, and a protease is introduced.
      Following the digestion, the peptides are cleaned up using the tip's hydrophobic
      part. The methodology allows processing of protein loads down to the low
      microgram/submicrogram levels. The detergent removal takes about 5 min, whereas
      the tryptic proteolysis of a cellular lysate is complete in as little as 30 min.
      We have successfully utilized the method for analysis of cellular lysates,
      enriched membrane preparations, and immunoprecipitates. We expect that due to its
      robustness and simplicity, the method will become an essential proteomics tool. 

PMID- 24678028
TI  - Health-related quality of life: two decades after liver transplantation.
AB  - In this study, we describe a cohort of patients who received liver transplants
      before January 1, 1989 at the University of Minnesota Medical Center (UMMC), and
      we evaluate the health-related quality of life (HRQOL) of the survivors of this
      group. One hundred sixty-one patients--66 adults and 95 children--received whole
      deceased donor liver transplants. Thirteen transplants occurred before 1980, and
      all these patients died within 6 months; they were excluded from the survival
      analysis because they came from the pre-cyclosporine era. The survival rates at
      1, 5, 10, and 20 years were 72%, 57%, 49%, and 37%, respectively (34% when pre
      1980 patients were included). The median survival time was approximately 10 years
      for adult and pediatric recipients. The causes of death were ascertained by chart
      reviews. Technical failures were common between the years 1980 and 1984, and they
      decreased to 0% by 1988. As for HRQOL, 53 patients (36%) survived and were
      contacted to complete a 12-item health survey [Short Form 12 (SF-12)].
      Retransplants were excluded. Sixty-eight percent returned the SF-12 survey. The
      median age for all respondents was 31.4 years: the median was 67.4 years for
      adult survivors and 28.8 years for pediatric survivors. The Mental Component
      Summary (MCS) score was 54.6 for adult survivors and 48.6 for pediatric
      survivors. The Physical Component Summary (PCS) score was 39.3 for adult
      survivors and 49.2 for pediatric survivors. Both the MCS and the PCS were norm
      based to the US population with a mean of 50 and a standard deviation of 10. In
      conclusion, 35.8% of liver transplant recipients from UMMC were alive 20 years
      after liver transplantation. Technical failure-related deaths decreased
      dramatically from 1980 to 1988. The mental health of pediatric and adult
      survivors was similar to that of the general population. The physical health of
      the pediatric survivors was equivalent to that of the general population, but it
      was slightly less than what was expected with adjustments for age. The physical
      health of the adult survivors was approximately 1 standard deviation below that
      of the general population.

PMID- 24678029
TI  - Total synthesis of the putative structure of xylarinol B.
AB  - The total synthesis of the putative structure of xylarinol B is described and the
      need to revise its structure is demonstrated. The central benzoxepine skeleton
      was constructed by employing a cobalt-mediated bimolecular [2+2+2] Reppe
      Vollhardt alkyne cycloaddition reaction. 

PMID- 24678030
TI  - Precisely patterning graphene sheets through a liquid-bridge induced strategy.

PMID- 24678031
TI  - Validation of 31 of the most commonly used immunohistochemical antibodies in
      cytology prepared using the Cellient((r)) automated cell block system.
AB  - The Cellient((r)) cell block system has become available as an alternative,
      partially automated method to create cell blocks in cytology. We sought to show a
      validation method for immunohistochemical (IHC) staining on the Cellient cell
      block system (CCB) in comparison with the formalin fixed paraffin embedded
      traditional cell block (TCB). Immunohistochemical staining was performed using 31
      antibodies on 38 patient samples for a total of 326 slides. Split samples were
      processed using both methods by following the Cellient((r)) manufacturer's
      recommendations for the Cellient cell block (CCB) and the Histogel method for
      preparing the traditional cell block (TCB). Interpretation was performed by three
      pathologists and two cytotechnologists. Immunohistochemical stains were scored
      as: 0/1+ (negative) and 2/3+ (positive). Inter-rater agreement for each antibody
      was evaluated for CCB and TCB, as well as the intra-rater agreement between TCB
      and CCB between observers. Interobserver staining concordance for the TCB was
      obtained with statistical significance (P < 0.05) in 24 of 31 antibodies.
      Interobserver staining concordance for the CCB was obtained with statistical
      significance in 27 of 31 antibodies. Intra-observer staining concordance between
      TCB and CCB was obtained with statistical significance in 24 of 31 antibodies
      tested. In conclusions, immunohistochemical stains on cytologic specimens
      processed by the Cellient system are reliable and concordant with stains
      performed on the same split samples processed via a formalin fixed-paraffin
      embedded (FFPE) block. The Cellient system is a welcome adjunct to cytology work
      flow by producing cell block material of sufficient quality to allow the use of
      routine IHC.

PMID- 24678032
TI  - In situ synthesis of nanocomposite membranes: comprehensive improvement strategy
      for direct methanol fuel cells.
AB  - In situ synthesis is a powerful approach to control nanoparticle formation and
      consequently confers extraordinary properties upon composite membranes relative
      to conventional doping methods. Herein, uniform nanoparticles of cesium hydrogen
      salts of phosphotungstic acid (CsPW) are controllably synthesized in situ in
      Nafion to form CsPW-Nafion nanocomposite membranes with both improved proton
      conductivity and methanol-crossover suppression. A 101.3% increase of maximum
      power density has been achieved relative to pristine Nafion in a direct methanol
      fuel cell (DMFC), indicating a potential pathway for large-scale fabrication of
      DMFC alternative membranes.

PMID- 24678033
TI  - Computational and experimental insight into the molecular mechanism of
      carboxamide inhibitors of succinate-ubquinone oxidoreductase.
AB  - Succinate-ubiquinone oxidoreductase (SQR, EC 1.3.5.1), also known as
      mitochondrial respiratory complex II or succinate dehydrogenase (SDH), catalyzes
      the oxidation of succinate to fumarate as part of the tricarboxylic acid cycle.
      SQR has been identified as a novel target of a large family of agricultural
      fungicides. However, the detailed mechanism of action between the fungicides and
      SQR is still unclear, and the bioactive conformation of fungicides in the SQR
      binding pocket has not been identified. In this study, the kinetics of porcine
      SQR inhibition by ten commercial carboxamide fungicides were measured, and
      noncompetitive inhibition was observed with respect to succinate, DCIP, and
      cytochrome c, while competitive inhibition was observed with respect to
      ubiquinone. With the aim to uncover the binding conformation of these fungicides,
      molecular docking, molecular dynamics simulation, and molecular mechanics/Poisson
      Boltzmann surface area (MM/PBSA) calculations were then performed. The excellent
      correlation (r(2) =0.94) between the calculated (DeltaGcal ) and experimental
      (DeltaGexp ) binding free energies indicates that the obtained docking
      conformation could be the bioactive conformation. The acid moiety of carboxamide
      fungicides inserts into the ubiquinone binding site (Q-site) of SQR, forming van
      der Waals (vdW) interactions with C_R46, C_S42, B_I218, and B_P169, while the
      amine moiety extends to the mouth of the Q-site, forming vdW interactions with
      C_W35, C_I43, and C_I30. The carbonyl oxygen atom of the carboxamide forms
      hydrogen bonds with B_W173 and D_Y91. These findings provide valuable information
      for the design of more potent and specific inhibitors of SQR. 

PMID- 24678034
TI  - Effectiveness of three-dimensional digital animation in teaching human anatomy in
      an authentic classroom context.
AB  - Three-dimensional (3D) digital animations were used to teach the human
      musculoskeletal system to first year kinesiology students. The purpose of this
      study was to assess the effectiveness of this method by comparing two groups from
      two different academic years during two of their official required anatomy
      examinations (trunk and upper limb assessments). During the upper limb section,
      the teacher used two-dimensional (2D) drawings embedded into PowerPoint((r))
      slides and 3D digital animations for the first group (2D group) and the second
      (3D group), respectively. The same 3D digital animations were used for both
      groups during the trunk section. The only difference between the two was the
      multimedia used to present the information during the upper limb section. The 2D
      group surprisingly outperformed the 3D group on the trunk assessment. On the
      upper limb assessment no difference in the scores on the overall anatomy
      examination was found. However, the 3D group outperformed the 2D group in
      questions requiring spatial ability. Data supported that 3D digital animations
      were effective instructional multimedia material tools in teaching human anatomy
      especially in recalling anatomical knowledge requiring spatial ability. The
      importance of evaluating the effectiveness of a new instructional material
      outside laboratory environment (e.g., after a complete semester and on official
      examinations) was discussed.

PMID- 24678035
TI  - A mini-review: Cell response to microscale, nanoscale, and hierarchical
      patterning of surface structure.
AB  - Cellular behavior can be influenced by the chemical and physical surface
      characteristics of biomedical substrates. To understand the relationships between
      various topographical surface patterns and cellular activities, various types of
      pattern models have been developed and examined in a range of sizes (microscale,
      nanoscale, and hierarchical structures consisting of both) and shapes (pillar,
      hole, groove, grate, grid, and island). Here, we review fabrication methods for
      obtaining physically patterned microscale and nanoscale surfaces, and discuss the
      relationships between cellular responses and physically patterned surfaces, which
      could be applied to various biomedical scaffolds used in tissue engineering
      applications.

PMID- 24678037
TI  - Phosphorus-containing materials for organic electronics.
AB  - Phosphorus-based materials have received widespread attention in recent years, in
      particular as possible candidates for practical application in organic
      electronics. The geometry and electronic nature of phosphorus make it a favorable
      heteroatom for property tuning in order to obtain better performing organic
      electronics. This Focus Review discusses recent structural modifications and
      syntheses of phosphorus-based materials, illustrates property tuning at the same
      time, and highlights specific examples for device applications. 

PMID- 24678036
TI  - Comparative proteomics and metallomics studies in Arabidopsis thaliana leaf
      tissues: evaluation of the selenium addition in transgenic and nontransgenic
      plants using two-dimensional difference gel electrophoresis and laser ablation
      imaging.
AB  - The main goal of this work is to evaluate some differential protein species in
      transgenic (T) and nontransgenic (NT) Arabidopsis thaliana plants after their
      cultivation in the presence or absence of sodium selenite. The transgenic line
      was obtained through insertion of CaMV 35S controlling nptII gene. Comparative
      proteomics through 2D-DIGE is carried out in four different groups (NT * T; NT *
      Se-NT (where Se is selenium); Se-NT * Se-T, and T * Se-T). Although no
      differential proteins are achieved in the T * Se-T group, for the others, 68
      differential proteins (by applying a regulation factor >=1.5) are achieved, and
      27 of them accurately characterized by ESI-MS/MS. These proteins are classified
      into metabolism, energy, signal transduction, disease/defense categories, and
      some of them are involved in the glycolysis pathway-Photosystems I and II and ROS
      combat. Additionally, laser ablation imaging is used for evaluating the Se and
      sulfur distribution in leaves of different groups, corroborating some results
      obtained and related to proteins involved in the glycolysis pathway. From these
      results, it is possible to conclude that the genetic modification also confers to
      the plant resistance to oxidative stress. 

PMID- 24678038
TI  - Anisotropic etching of graphite flakes with water vapor to produce armchair-edged
      graphene.
AB  - A one-step anisotropic etching method is developed to specifically obtain
      armchair-edged graphene directly from graphite flakes on various substrates. The
      armchair edge structure of the produced graphene is verified by the atomic
      resolution images obtained from the fluid mode peakforce tapping AFM and the
      relatively high intensity of D band in the Raman spectra. 

PMID- 24678039
TI  - Ciliated foregut cyst of the pancreas: a benign lesion with elevated CEA levels.

PMID- 24678040
TI  - Superior pseudocapacitive behavior of confined lignin nanocrystals for renewable
      energy-storage materials.
AB  - Strong demand for high-performance energy-storage devices has currently motivated
      the development of emerging capacitive materials that can resolve their critical
      challenge (i.e., low energy density) and that are renewable and inexpensive
      energy-storage materials from both environmental and economic viewpoints. Herein,
      the pseudocapacitive behavior of lignin nanocrystals confined on reduced graphene
      oxides (RGOs) used for renewable energy-storage materials is demonstrated. The
      excellent capacitive characteristics of the renewable hybrid electrodes were
      achieved by synergizing the fast and reversible redox charge transfer of surface
      confined quinone and the interplay with electron-conducting RGOs. Accordingly,
      pseudocapacitors with remarkable rate and cyclic performances (~96 % retention
      after 3000 cycles) showed a maximum capacitance of 432 F g(-1), which was close
      to the theoretical capacitance of 482 F g(-1) and sixfold higher than that of RGO
      (93 F g(-1)). The chemical strategy delineated herein paves the way to develop
      advanced renewable electrodes for energy-storage applications and understand the
      redox chemistry of electroactive biomaterials.

PMID- 24678042
TI  - The ATLAS project: The effects of a constructionist digital laboratory project on
      undergraduate laboratory performance.
AB  - Anatomical education is a dynamic field where developments in the implementation
      of constructive, situated-learning show promise in improving student achievement.
      The purpose of this study was to examine the effectiveness of an individualized,
      technology heavy project in promoting student performance in a combined anatomy
      and physiology laboratory course. Mixed-methods research was used to compare two
      cohorts of anatomy laboratories separated by the adoption of a new laboratory
      atlas project, which were defined as preceding (PRE) and following the adoption
      of the Anatomical Teaching and Learning Assessment Study (ATLAS; POST). The ATLAS
      project required the creation of a student-generated, photographic atlas via
      acquisition of specimen images taken with tablet technology and digital
      microscope cameras throughout the semester. Images were transferred to laptops,
      digitally labeled and photo edited weekly, and compiled into a digital book using
      Internet publishing freeware for final project submission. An analysis of
      covariance confirmed that student final examination scores were improved (P <
      0.05) following the implementation of the laboratory atlas project (PRE, n = 75;
      POST, n = 90; means +/- SE; 74.9 +/- 0.9 versus 78.1 +/- 0.8, respectively) after
      controlling for cumulative student grade point average. Analysis of
      questionnaires collected (n = 68) from the post group suggested students
      identified with atlas objectives, appreciated the comprehensive value in final
      examination preparation, and the constructionism involved, but recommended
      alterations in assignment logistics and the format of the final version.
      Constructionist, comprehensive term-projects utilizing student-preferred
      technologies could be used to improve performance toward student learning
      outcomes.

PMID- 24678041
TI  - Towards matched pairs of porphyrin-Re(I) /(99m) Tc(I) conjugates that combine
      photodynamic activity with fluorescence and radio imaging.
AB  - We recently prepared two novel water soluble porphyrins bearing a single
      peripheral chelator, either diethylenetriamine (1) or bipyridyl (2), tethered to
      one meso position. The preparation of their conjugates with a fac-{(99m) Tc(CO)3
      }(+) fragment and the potential of these resulting conjugates as fluorescence and
      radio imaging tools were also described. In this work, we focused on the
      corresponding non-radioactive analogues that bear the fac-{Re(CO)3 }(+) fragment
      (diethylenetriamine 3 and bipyridyl 4). We report on the uptake, in vitro PDT
      activity, and cellular localization of Re(I) conjugates 3 and 4 in comparison to
      the parent porphyrins 1 and 2. Compounds 1-4 have modest or negligible
      cytotoxicity in the dark against HeLa human cervical cancer cells but become
      remarkably cytotoxic after exposure to moderate doses of red visible light (590
      700 nm). This phototoxicity was found to be directly proportional to the total
      light dose. Although the four compounds show distinct uptake patterns, they have
      comparable PDT activity. Confocal fluorescence measurements showed that porphyrin
      1 and its Re(I) conjugate 3 have different cellular localization patterns in HeLa
      cells.

PMID- 24678043
TI  - The influence of the framework: an anion-binding study using fused
      [n]polynorbornanes.
AB  - A series of bis-thiourea-functionalized [n]polynorbornane hosts (1-6) with
      increasing size were synthesized and their anion-binding properties were
      evaluated by using 1H NMR spectroscopic titration and Job's plot analysis. The
      larger bis-thiourea-[3]polynorbornane scaffolds 4 and 5 bound acetate in a 1:1
      (cooperative) arrangement, whereas the corresponding smaller norbornane host 2,
      identical in preorganization, bound acetate in a 1:2 (independent) arrangement.
      In contrast, the size of the framework had no influence on the binding of
      dihydrogenphosphate. These results clearly highlight the subtle influence that
      the framework itself can have on host-guest interactions.

PMID- 24678044
TI  - Shedding light on black boxes in protein identification.
AB  - Performing a well thought-out proteomics data analysis can be a daunting task,
      especially for newcomers to the field. Even researchers experienced in the
      proteomics field can find it challenging to follow existing publication
      guidelines for MS-based protein identification and characterization in detail.
      One of the primary goals of bioinformatics is to enable any researcher to
      interpret the vast amounts of data generated in modern biology, by providing user
      friendly and robust end-user applications, clear documentation, and corresponding
      teaching materials. In that spirit, we here present an extensive tutorial for
      peptide and protein identification, available at
      http://compomics.com/bioinformatics-for-proteomics. The material is completely
      based on freely available and open-source tools, and has already been used and
      refined at numerous international courses over the past 3 years. During this
      time, it has demonstrated its ability to allow even complete beginners to
      intuitively conduct advanced bioinformatics workflows, interpret the results, and
      understand their context. This tutorial is thus aimed at fully empowering users,
      by removing black boxes in the proteomics informatics pipeline. 

PMID- 24678045
TI  - Exposure to traffic and early life respiratory infection: A cohort study.
AB  - We examined whether proximity to a major roadway and traffic density around the
      home during pregnancy are associated with risk of early life respiratory
      infection in a pre-birth cohort in the Boston area. We geocoded addresses for
      1,263 mother-child pairs enrolled during the first trimester of pregnancy in
      Project Viva during 1999-2002. We calculated distance from home to nearest major
      roadway and traffic density in a 100 m buffer around the home. We defined
      respiratory infection as maternal report of >=1 doctor-diagnosed pneumonia,
      bronchiolitis, croup, or other respiratory infection from birth until the early
      childhood visit (median age 3.3). We used relative risk regression models
      adjusting for potential confounders to estimate associations between traffic
      exposures and risk of respiratory infection. Distance to roadway during pregnancy
      was associated with risk of respiratory infection. In fully adjusted models,
      relative risks (95% CI) for respiratory infection were: 1.30 (1.08, 1.55) for
      <100 m, 1.15 (0.93, 1.41) for 100 to <200 m, and 0.95 (0.84, 1.07) for 200 to
      <1,000 m compared with living >=1,000 m away from a major roadway. Each
      interquartile range increase in distance to roadway was associated with an 8%
      (95% CI 0.87, 0.98) lower risk, and each interquartile range increase in traffic
      density was associated with a 5% (95% CI 0.98, 1.13) higher risk of respiratory
      infection. Our findings suggest that living close to a major roadway during
      pregnancy may predispose the developing lung to infection in early life. Pediatr
      Pulmonol. 2015; 50:252-259. (c) 2014 Wiley Periodicals, Inc.

PMID- 24678046
TI  - Rice husk-derived graphene with nano-sized domains and clean edges.
AB  - A new synthetic method is demonstrated for transforming rice husks into bulk
      amounts of graphene through its calcination and chemical activation. The bulk
      sample consists of crystalline nano-sized graphene and corrugated individual
      graphene sheets; the material generally contains one, two, or a few layers, and
      corrugated graphene domains are typically observed in monolayers containing
      topological defects within the hexagonal lattice and edges. Both types of
      graphenes exhibit atomically smooth surfaces and edges. 

PMID- 24678047
TI  - Catalytic amination of biomass-based alcohols.

PMID- 24678048
TI  - The intermingled history of occupational therapy and anatomical education: A
      retrospective exploration.
AB  - Few research articles have addressed the anatomical needs of entry-level
      occupational therapy students. Given this paucity of empirical evidence, there is
      a lack of knowledge regarding anatomical education in occupational therapy. This
      article will primarily serve as a retrospective look at the inclusion of
      anatomical education in the occupational therapy curriculum. Focusing on the
      historical inclusion is the first step to address the gap in existing knowledge.
      Examining the history of anatomy in occupational therapy provides an educational
      context for curricular developments and helps current anatomical educators
      understand the evolution of occupational therapy as a profession. Exploring the
      educational history also offers anatomy educators an identity, as significant
      contributors, in the training and preparedness of entry-level professionals while
      focusing on the ideals of occupational therapy. However, there is a critical need
      for empirical evidence of best teaching practices in occupational therapy and
      anatomical education. This manuscript provides a foundation and a starting point
      for further investigation into the anatomical competencies for entry-level
      occupational therapists.

PMID- 24678049
TI  - Coordination-driven hierarchical assembly of silver nanoparticles on MoS2
      nanosheets for improved lithium storage.
AB  - We report a novel strategy for the hierarchical assembly of Ag nanoparticles
      (NPs) on MoS2 nanosheets through coordination by using a multifunctional organic
      ligand. The presence of Ag NPs on the surface of MoS2 nanosheets inhibits their
      agglomeration, thereby providing increased interlayer spacing for easy Li(+) ion
      intercalation. Such a unique hybrid architecture also ensures sufficient
      percolation pathways on the whole surface of the MoS2 nanosheets. Moreover, the
      high rigidity and low deformability of the Ag NPs effectively preserve the hybrid
      architecture during the charge-discharge process, which translates into a high
      cycle stability. A prominent synergistic effect between MoS2 and Ag is witnessed.
      When the Ag content is only 5 wt %, the Ag-MoS2 hybrid delivers a reversible
      capacity as high as 920 mA h g(-1) at a current density of 100 mA g(-1), making
      the Ag-MoS2 hybrid an attractive candidate for next-generation LIBs.

PMID- 24678050
TI  - Electrospun nanofibers as dressings for chronic wound care: advances, challenges,
      and future prospects.
AB  - Chronic non-healing wounds show delayed and incomplete healing processes and in
      turn expose patients to a high risk of infection. Treatment currently focuses on
      dressings that prevent microbial infiltration and keep a balanced moisture and
      gas exchange environment. Antibacterial delivery from dressings has existed for
      some time, with responsive systems now aiming to trigger release only if
      infection occurs. Simultaneously, approaches that stimulate cell proliferation in
      the wound and encourage healing have been developed. Interestingly, few dressings
      appear capable of simultaneously impairing or treating infection and encouraging
      cell proliferation/wound healing. Electrospinning is a simple, cost-effective,
      and reproducible process that can utilize both synthetic and natural polymers to
      address these specific wound challenges. Electrospun meshes provide high-surface
      area, micro-porosity, and the ability to load drugs or other biomolecules into
      the fibers. Electrospun materials have been used as scaffolds for tissue
      engineering for a number of years, but there is surprisingly little literature on
      the interactions of fibers with bacteria and co-cultures of cells and bacteria.
      This Review examines the literature and data available on electrospun wound
      dressings and the research that is required to develop smart multifunctional
      wound dressings capable of treating infection and healing chronic wounds. 

PMID- 24678051
TI  - Glucose tolerance affects pubertal growth and final height of children with
      cystic fibrosis.
AB  - There are few data about the impact of cystic fibrosis-related diabetes (CFRD) on
      growth. We analyzed 17 children with cystic fibrosis (CF) presenting with newly
      diagnosed CFRD during puberty, in comparison with a matched control group of 52
      CF children with normal glucose tolerance (NGT). Anthropometric evaluation showed
      that body mass index at CFRD diagnosis was significantly reduced in children with
      CFRD, in comparison with children with NGT (CFRD: -0.48 +/- 1.08 vs. NGT: 0.2 +/-
      0.99; P=0.01), and the same difference remained evident at the end of follow up
      (CFRD: -0.49 +/- 0.95 vs. NGT: 0.13 +/- 0.89; P=0.04). Height standard deviation
      score (SDS) at baseline was slightly but not significantly lower in CFRD children
      (CFRD: -0.71 +/- 0.83 vs. NGT: -0.25 +/- 1.08; P=0.08), while final height SDS
      was significantly reduced (CFRD: -1.61 +/- 1.12 vs. NGT: -0.61 +/- 1.15;
      P=0.003). Mean final height SDS of the whole group was lower than mean target
      height SDS (final height SDS: -0.86 +/- 1.2 vs. target height SDS: -0.3 +/- 0.85;
      P<0.001). Target adjusted final height was lower in CFRD children, although the
      difference between CFRD and NGT children did not reach statistical significance
      (CFRD: -0.8 +/- 1.03 vs. NGT: -0.47 +/- 0.9; P=0.09). Pubertal growth and final
      height are negatively affected by CFRD. Intensive insulin treatment does not
      appear to be effective in normalizing growth, even when treatment is started
      early in the course of the disease, before the onset of clinical deterioration.

PMID- 24678052
TI  - Porphyrin-based design of bioinspired multitarget quadruplex ligands.
AB  - Secondary nucleic acid structures, such as DNA and RNA quadruplexes, are
      potential targets for cancer therapies. Ligands that interact with these targets
      could thus find application as anticancer agents. Synthetic G-quartets have
      recently found numerous applications, including use as bioinspired G-quadruplex
      ligands. Herein, the design, synthesis and preliminary biophysical evaluation of
      a new prototype multitarget G-quadruplex ligand, (PNA)PorphySQ, are reported,
      where peptidic nucleic acid guanine ((PNA)G) was incorporated in the porphyrin
      templated synthetic G-quartet (PorphySQ). Using fluorescence resonance energy
      transfer (FRET)-melting experiments, PorphySQ was shown to possess enhanced
      quadruplex-interacting properties thanks to the presence of four positively
      charged (PNA)G residues that improve its electrostatic interactions with the
      binding site of both DNA and RNA quadruplexes (i.e., their negatively charged and
      accessible G-quartets), thereby making (PNA)PorphySQ an interesting prototype of
      a multitarget ligand. Both the chemical stability and water solubility of
      (PNA)PorphySQ are improved over the non-PNA derivative (PorphySQ), which are
      desirable properties for drug development, and while improvements remain to be
      made, this ligand is a promising lead for the further development of multitarget
      G-quadruplex ligands.

PMID- 24678053
TI  - Two-photon-triggered drug delivery via fluorescent nanovalves.

PMID- 24678055
TI  - Substitutional doping of carbon nanotubes with heteroatoms and their chemical
      applications.
AB  - The electronic properties of carbon nanotubes (CNTs) can be tuned by
      substitutional doping with heteroatoms (mainly B and N) to expand the
      applications of CNTs. Based on the comprehensive understanding of the
      substitutional doping of CNTs, it should be possible to deliberately design doped
      CNTs for specific purposes. Thus, relevant experimental and theoretical works are
      reviewed herein in an attempt to correlate the synthetic methods, electronic
      properties, and applications of heteroatom-doped CNTs. The distribution and
      arrangement of heteroatoms in the graphitic lattice of CNTs can be modulated
      through the choice of synthetic conditions, which would further lead to different
      electronic properties of CNTs for their chemical applications. 

PMID- 24678054
TI  - Susceptibility to distraction in autism spectrum disorder: probing the integrity
      of oscillatory alpha-band suppression mechanisms.
AB  - When attention is directed to one information stream over another, the brain can
      be configured in advance to selectively process the relevant stream and suppress
      potentially distracting inputs. One key mechanism of suppression is through the
      deployment of anticipatory alpha-band (~10 Hz) oscillatory activity, with greater
      alpha-band power observed in cortical regions that will ultimately process the
      distracting stream. Atypical attention has been implicated in autism spectrum
      disorder (ASD), including greater interference by distracting task-irrelevant
      inputs. Here we tested the integrity of these alpha-band mechanisms in ASD using
      an intersensory attention task. Electroencephalography (EEG) was recorded while
      participants were cued on a trial-by-trial basis to selectively deploy attention
      to the visual or auditory modality in anticipation of a target within the cued
      modality. Whereas typically developing (TD) children showed the predicted alpha
      band modulation, with increased alpha-band power over parieto-occipital scalp
      when attention was deployed to the auditory compared with the visual modality,
      this differential pattern was entirely absent at the group level in the ASD
      cohort. Further, only the ASD group showed impaired performance due to the
      presence of task-irrelevant sensory information. These data suggest that impaired
      modulation of alpha-band activity plays a role in increased distraction from
      extraneous sensory inputs in ASD.

PMID- 24678056
TI  - Consequences of block sequence on the orthogonal folding of triblock copolymers.
AB  - ABA- and BAB-type triblock copolymers possessing pendant, self-assembling motifs
      in the A and B blocks were synthesized, with 2-ureidopyrimidinone (UPy) and
      benzene-1,3,5-tricarboxamide (BTA) for the A and B block, respectively. They were
      investigated to assess if and how the polymer's microstructure influences the
      self-assembly behavior of the supramolecular motifs and, as a result, the single
      chain folding process. BAB-type triblock copolymers were synthesized via atom
      transfer radical polymerization (ATRP) with molecular weights ranging from 30 to
      120 kg mol-1; the BTA and UPy motifs were attached using a post-functionalization
      approach. The ABA-type triblock copolymers were available from previous work. In
      highly dilute solutions, both types of triblock copolymers fold into single-chain
      polymeric nanoparticles (SCPNs) via thermally induced BTA self-assembly and photo
      triggered UPy dimerization. Chain collapse induced by intramolecular UPy
      dimerization was evaluated using size-exclusion chromatography (SEC). The BTA
      self-assembly was monitored by circular dichroism (CD) spectroscopy. The
      microstructures of SCPNs were visualized by atomic force microscopy (AFM). SEC
      analysis indicated a more loose packing for the BAB-type folded nanoparticles
      than for the ABA-type ones, which implies that topological differences in the
      polymer architecture do affect the folding behavior, although only slightly. The
      facile synthetic protocol developed here provides topologically different
      triblock architectures and opens up the area for single-chain folding technology
      that is applicable in artificial enzymatic systems with compartmentalized
      domains.

PMID- 24678058
TI  - Gender differences in objectively assessed physical activity in asthmatic and non
      asthmatic children.
AB  - OBJECTIVE: To compare objectively assessed physical activity levels, between
      asthmatic children and non-asthmatic controls. METHODS: From a random community
      sample of 794 children aged 8-9 years, in a case-control design, 104 children
      with ever doctor's diagnosis of asthma and 99 non-asthmatic controls were
      recruited and had assessment of physical activity with biaxial accelerometers for
      7 days. RESULTS: Children with active (also reporting at least one episode of
      wheezing in the last 12 months) and inactive (no wheezing in past 12 months)
      asthma appeared to have similar physical activity and sedentary activity levels
      compared to non-asthmatic children. However, girls with active asthma had
      significantly lower moderate-to-vigorous physical activity (MVPA) levels than
      their peers with adjusted geometric mean ratio of 0.59 (95% CI: 0.369, 0.929, P
      value = 0.024). No difference in physical and sedentary activity levels was
      observed between asthmatic and non-asthmatic boys. The difference between genders
      in the comparison of MVPA levels in asthmatics and controls was statistically
      significant (P-value of likelihood ratio test [LRT] for effect modification by
      gender = 0.034). CONCLUSIONS: Unlike boys, girls with active asthma appear to be
      less active than their healthy peers, and this gender difference might explain
      the inconsistent evidence from previous reports on physical activity levels in
      asthmatic children. Further studies are needed to confirm the gender interaction
      in the childhood asthma-physical activity relation and the implications on
      current guidelines for physical exercise prescriptions in asthmatic children.

PMID- 24678059
TI  - Effects of the tumor-vasculature-disrupting agent verubulin and two heteroaryl
      analogues on cancer cells, endothelial cells, and blood vessels.
AB  - Two analogues of the discontinued tumor vascular-disrupting agent verubulin
      (Azixa(r), MPC-6827, 1) featuring benzo-1,4-dioxan-6-yl (compound 5 a) and N
      methylindol-5-yl (compound 10) residues instead of the para-anisyl group on the 4
      (methylamino)-2-methylquinazoline pharmacophore, were prepared and found to
      exceed the antitumor efficacy of the lead compound. They were antiproliferative
      with single-digit nanomolar IC50 values against a panel of nine tumor cell lines,
      while not affecting nonmalignant fibroblasts. Indole 10 surpassed verubulin in
      seven tumor cell lines including colon, breast, ovarian, and germ cell cancer
      cell lines. In line with docking studies indicating that compound 10 may bind the
      colchicine binding site of tubulin more tightly (Ebind =-9.8 kcal mol(-1) ) than
      verubulin (Ebind =-8.3 kcal mol(-1) ), 10 suppressed the formation of vessel-like
      tubes in endothelial cells and destroyed the blood vessels in the chorioallantoic
      membrane of fertilized chicken eggs at nanomolar concentrations. When applied to
      nude mice bearing a highly vascularized 1411HP germ cell xenograft tumor,
      compound 10 displayed pronounced vascular-disrupting effects that led to
      hemorrhages and extensive central necrosis in the tumor.

PMID- 24678060
TI  - Nano-intermetallic AuCu3 catalyst for oxygen reduction reaction: performance and
      mechanism.
AB  - This paper introduces a new approach for catalyst design using the non-precious
      metal Cu as one of the catalytic active centers. This differs from previous
      studies that considered precious metals to be responsible for the catalytic
      reaction in precious alloys. Intermetallic AuCu3/C nanoparticles with a diameter
      of 3 nm were developed for the first time, with uniform dispersion and a narrow
      size distribution. The ca. 3 nm as-synthesised AuCu3/C showed superior catalytic
      performance for oxygen reduction reactions (ORR) in alkaline solutions, with
      comparable half-wave potential and 1.5 times mass current density of commercial
      Pt/C at 0.80 V (vs. reversible hydrogen electrode (RHE)). The advanced catalytic
      activities are mainly attributed to the synergetic effects of electro-active
      atomic Au and Cu on the particle surface, in which Cu helps to activate the O2
      molecule and Au benefits OH(-) desorption. The excellent durability and methanol
      tolerance exhibited in alkaline solutions provide another advantage for AuCu3/C
      to be considered as a potential alternative cathode catalyst in alkaline fuel
      cells.

PMID- 24678057
TI  - Bioreducible polycations in nucleic acid delivery: past, present, and future
      trends.
AB  - Polycations that are degradable by reduction of disulfide bonds are developed for
      applications in delivery of nucleic acids. This Feature Article surveys methods
      of synthesis of bioreducible polycations and discusses current understanding of
      the mechanism of action of bioreducible polyplexes. Emphasis is placed on the
      relationship between the biological redox environment and toxicity, trafficking,
      transfection activity, and in vivo behavior of bioreducible polycations and
      polyplexes. 

PMID- 24678061
TI  - From PCP to MXE: a comprehensive review of the non-medical use of dissociative
      drugs.
AB  - PCP or phencyclidine was discovered in 1956 and soon became a popular street
      drug. Dissociatives including PCP, ketamine, and dextromethorphan have been used
      non-medically for their mind-altering effects for over 60 years. Many of these
      compounds have also been used clinically and in legitimate research. At least 14
      derivatives of PCP were sold for non-medical and illict use from the late 1960s
      until the 1990s. With the advent of the Internet, the drug market underwent a
      dramatic evolution. While initially gray-market chemical vendors offering
      dextromethorphan and ketamine thrived, most recently the market has shifted to
      legal high and online-based research chemical vendors. Starting with the first
      dissociative research chemical, 4-MeO-PCP in 2008, the dissociative research
      chemical market has rapidly evolved and currently comprises at least 12
      dissociatives, almost half of which were unknown in the scientific literature
      prior to their introduction. Several of these, including methoxetamine, have
      reached widespread use internationally. A historical account of non-medical use
      of over 30 dissociative compounds was compiled from a diverse collection of
      sources. The first complete portrait of this underground market is presented
      along with the relevant legal, technological, and scientific developments which
      have driven its evolution.

PMID- 24678062
TI  - Sustainable production of green feed from carbon dioxide and hydrogen.
AB  - Carbon dioxide hydrogenation to form hydrocarbons was conducted on two iron-based
      catalysts, prepared according to procedures described in the literature, and on a
      new iron spinel catalyst. The CO2 conversion measured in a packed-bed reactor was
      limited to about 60% because of excessive amounts of water produced in this
      process. Switching to a system of three packed-bed reactors in series with
      interim removal of water and condensed hydrocarbons increased CO2 conversion to
      as much as 89%. The pure spinel catalyst displayed a significantly higher
      activity and selectivity than those of the other iron catalysts. This process
      produces a product called green feed, which is similar in composition to the
      product of a high-temperature, iron-based Fischer-Tropsch process from syngas.
      The green feed can be readily converted into renewable fuels by well-established
      technologies.

PMID- 24678063
TI  - Fullerene sugar balls: a new class of biologically active fullerene derivatives.
AB  - Among the large variety of bioactive C60 derivatives, fullerene derivatives
      substituted with sugar residues, that is, glycofullerenes, are of particular
      interest. The sugar residues are not only solubilizing groups; their intrinsic
      biological properties also provide additional appealing features to the
      conjugates. The most recent advances in the synthesis and the biological
      applications of glycofullerenes are summarized in the present review article with
      special emphasis on globular glycofullerenes, that is, fullerene sugar balls,
      constructed on a hexa-substituted fullerene scaffold. The high local
      concentration of carbohydrates around the C60 core in fullerene sugar balls is
      perfectly suited to the binding of lectins through the "glycoside cluster
      effect", and these compounds are potential anti-adhesive agents against bacterial
      infection. Moreover, mannosylated fullerene sugar balls have shown antiviral
      activity in an Ebola pseudotyped infection model. Finally, when substituted with
      peripheral iminosugars, dramatic multivalent effects have been observed for
      glycosidase inhibition. These unexpected observations have been rationalized by
      the interplay of interactions involving the catalytic site of the enzyme and non
      glycone binding sites with lectin-like abilities. 

PMID- 24678064
TI  - Topical cocaine vs adrenaline in endoscopic sinus surgery: a blinded randomized
      controlled study.
AB  - BACKGROUND: Adequate surgical field visualization is among the most important
      factors in preventing complications in functional endoscopic sinus surgery
      (FESS). The aim of this study was to assess the effect of topical cocaine vs
      adrenaline on surgical field visualization and intraoperative bleeding during
      FESS. METHODS: A randomized controlled trial was conducted. A total of 37
      patients that underwent FESS for chronic rhinosinusitis were randomized to the
      side of the nose that received adrenaline or cocaine-soaked patties, and the side
      that was operated first. The surgeon evaluating the bleeding was blinded to the
      vasoconstrictor allocation. At the commencement of surgery and at regular 15
      minute intervals, the operating surgeon evaluated the extent of bleeding in the
      operative field according to a validated scale. At each assessment, mean arterial
      pressure (MAP), heart rate, and end tidal CO2 were also recorded. At the end of
      each side, total blood loss was measured. RESULTS: There was no difference in the
      mean surgical field scores between the adrenaline and cocaine sides (2.04 +/-
      0.75 vs 2.17 +/- 0.7, p = 0.24), nor the total blood loss (p = 0.43). On the
      cocaine side, there was a correlation between surgical field grade and duration
      of surgery (p < 0.05) as well as blood loss (p < 0.05) and MAP (p < 0.05).
      CONCLUSION: There is no difference in the quality of the surgical field achieved
      through the use of topical cocaine or adrenaline during FESS. Either of these
      agents can be effectively used for topical decongestion at the onset of surgery.

PMID- 24678065
TI  - Multifunctional organized mesoporous tin oxide films templated by graft
      copolymers for dye-sensitized solar cells.
AB  - The synthesis of organized mesoporous SnO2 films with high porosity, larger
      pores, and good interconnectivity, obtained by sol-gel templating with an
      amphiphilic graft copolymer, poly(vinyl chloride)-graft-poly(oxyethylene
      methacrylate), is reported. An improved performance of dye-sensitized solar cells
      (DSSCs) is demonstrated by the introduction of a 400 nm thick organized
      mesoporous SnO2 interfacial (om-SnO2 IF) layer between nanocrystalline TiO2 (nc
      TiO2 ) and a fluorine-doped tin oxide substrate. To elucidate the improved
      efficiency, the structural, optical, and electrochemical properties of the
      devices were characterized by SEM, UV/Vis spectroscopy, noncontact 3D surface
      profilometry, intensity-modulated photocurrent/voltage spectroscopy, incident
      photon-to-electron conversion efficiency, and electrochemical impedance
      spectroscopy measurements. The energy-conversion efficiency of the solid
      polymerized ionic liquid based DSSC fabricated with the om-SnO2 IF/nc-TiO2
      photoanode reached 5.9% at 100 mW cm(-2) ; this is higher than those of neat nc
      TiO2 (3.5%) and organized mesoporous TiO2 interfacial/nc-TiO2 layer (5.4%)
      photoanodes. The improved efficiency is attributed to the antireflective
      property, cascadal energy band gap, good interconnectivity, and high electrical
      conductivity of the om-SnO2 IF layer, which results in enhanced light harvesting,
      increased electron transport, reduced charge recombination, and decreased
      interfacial/internal resistance.

PMID- 24678066
TI  - Early and late complications of endoscopic hemostatic techniques following
      different carotid artery injury characteristics.
AB  - BACKGROUND: The most dreaded hemorrhagic complication in endoscopic endonasal
      surgery is injury to the internal carotid artery (ICA). Although a number of
      treatment protocols are currently used, none have been formally investigated.
      This study aims to compare the efficacy of the muscle patch, bipolar diathermy,
      and aneurysm clip on hemostasis, pseudoaneurysm formation, and long-term vessel
      patency for different injury types in a sheep model of carotid bleeding. METHODS:
      Twenty-seven sheep underwent ICA dissection/isolation followed by the artery
      placement within a modified "sinus model otorhino neuro trainer" (SIMONT) model.
      Standardized linear, punch, and stellate injuries were made. Randomization of
      sheep to receive 1 of 3 hemostatic techniques was performed (muscle, bipolar,
      clip). Specific outcome measures included attainment of primary hemostasis, time
      to hemostasis, blood loss, pseudoaneurysm formation, and carotid patency on
      follow-up magnetic resonance imaging (MRI). RESULTS: Bipolar achieved primary
      hemostasis in 7 of 9 cases and 2 cases of secondary hemorrhage. It had no
      associated pseudoaneurysm formation. Carotid patency was variable on follow-up
      MRI. Muscle patch achieved 100% primary hemostasis with 2 cases of secondary
      hemorrhage. There were 2 cases of pseudoaneurysm and 100% patency rate on follow
      up MRI. Aneurysm clip achieved 100% primary hemostasis with 1 case of secondary
      hemorrhage. No pseudoaneurysm formation and a 50% rate of carotid insufficiency
      on MRI. CONCLUSION: This study shows that the crushed muscle patch and aneurysm
      clip can be viable options in the management of ICA injury with short-term and
      long-term benefits. Complications associated with these techniques were
      comparable if not reduced when compared to the published literature.

PMID- 24678067
TI  - Electrochemical performance of hierarchical porous carbon materials obtained from
      the infiltration of lignin into zeolite templates.
AB  - Hierarchical porous carbon materials prepared by the direct carbonization of
      lignin/zeolite mixtures and the subsequent basic etching of the inorganic
      template have been electrochemically characterized in acidic media. These lignin
      based templated carbons have interesting surface chemistry features, such as a
      variety of surface oxygen groups and also pyridone and pyridinic groups, which
      results in a high capacitance enhancement compared to petroleum-pitch-based
      carbons obtained by the same procedure. Furthermore, they are easily electro
      oxidized in a sulfuric acid electrolyte under positive polarization to produce a
      large amount of surface oxygen groups that boosts the pseudocapacitance. The
      lignin-based templated carbons showed a specific capacitance as high as 250 F g(
      1) at 50 mA g(-1) , with a capacitance retention of 50 % and volumetric
      capacitance of 75 F cm(-3) at current densities higher than 20 A g(-1) thanks to
      their suitable porous texture. These results indicate the potential use of
      inexpensive biomass byproducts, such as lignin, as carbon precursors in the
      production of hierarchical carbon materials for electrodes in electrochemical
      capacitors. 

PMID- 24678069
TI  - Excited state properties of a short pi-electron conjugated peridinin analogue.
AB  - C29-peridinin is a synthetic analogue of the important, naturally-occurring
      carotenoid, peridinin, found in several marine algal species. C29-peridinin has
      five conjugated carbon-carbon double bonds compared to eight possessed by
      peridinin and also lacks the methyl group functionalities typically present along
      the polyene chain of carotenoids. These structural modifications lead to unique
      excited state properties and important insights regarding the factors controlling
      the photophysics of peridinin and other carbonyl-containing carotenoids, which
      are critical components of the light-harvesting systems of many photosynthetic
      organisms.

PMID- 24678068
TI  - Interleukin-7 receptor-alpha gene mutations are not detected in adult T-cell
      acute lymphoblastic leukemia.
AB  - Somatic mutations in cancer cell genes are classified according to their
      functional significance. Those that provide the malignant cells with significant
      advantage are collectively referred to as driver mutations and those that do not,
      are the passenger mutations. Accordingly, analytical criteria to distinguish
      driver mutations from passenger mutations have been recently suggested. Recent
      studies revealed mutations in interleukin-7 receptor-alpha (IL7R) gene in 10% of
      pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients and in only a few
      cases of pediatric B-ALL. IL7R mutations are also frequently found in patients
      with lung cancer, but whereas in pediatric T-ALL IL7R mutations are "drivers"
      (consisting of gain-of-function mutations within a narrow 50-base pair interval
      at exon 6 that confer cytokine-independent cell growth and promote tumor
      transformation), in lung cancer, mutations are substitution mutations randomly
      distributed across the gene and are probably only "passenger" events. Because the
      treatment response of adult T-ALL is significantly poorer than that of childhood
      T-ALL and because exon 6 IL7R mutations play a role in the pathogenesis of
      childhood T-ALL, we sought to determine how the pattern of IL7R mutations varies
      between adult and childhood T-ALL. To that end, we sequenced the 50-base pair
      interval in exon 6 of the IL7R of DNA obtained from bone marrow samples of 35
      randomly selected adult patients with T-ALL. Our analysis revealed that none of
      these 35 samples carried an IL7R mutation in exon 6. Whether differences in the
      genetic makeup of adult and childhood T-ALL explain the differential response to
      therapy remains to be determined.

PMID- 24678070
TI  - Effects of Losartan-based therapy on the incidence of end-stage renal disease and
      associated costs in type 2 diabetes mellitus: A retrospective cost-effectiveness
      analysis in the United Kingdom.
AB  - BACKGROUND: In the Reduction of Endpoints in Non-Insulin-Dependent Diabetes
      Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, the primary
      composite end point was the 2-fold increase in baseline serum creatinine
      concentration, the development of end-stage renal disease (ESRD), or death. The
      effects of losartan used for the prevention or delay of progression of diabetic
      nephropathy to ESRD were compared with those of conventional anti-hypertensive
      treatment (control) (calcium channel blockers, diuretics, alpha-blockers, beta
      blockers, and centrally acting agents), but not angiotensin-converting enzyme
      (ACE) inhibitors or angiotensin II antagonists (AIIAs), in 1513 adults with type
      2 diabetes mellitus (DM-2) and nephropathy. Both treatment groups received
      conventional antihypertensive therapy (calcium channel blockers, diuretics, alpha
      blockers, beta-blockers, and/or centrally acting agents). ACE inhibitors and
      AIIAs were not allowed during the study period. The relative risk (RR) for
      composite outcome was 25% less, and the RR for ESRD was 28% less, in the
      losartantreated group compared with the control group. OBJECTIVE: The aim of this
      retrospective cost-effectiveness analysis was to use data from the RENAAL study
      to determine the survival benefits and lifetime direct medical costs of a
      losartan-based regimen for the prevention of ESRD in patients with DM-2 and
      nephropathy in the setting of the UK National Health Service (NHS). METHODS: This
      analysis used life-years saved as the effectiveness measure. The effect of
      losartan-based treatment on ESRD risk was confined to the trial period (3.5
      years). However, survival and the lifetime direct medical costs of managing ESRD
      were projected beyond the trial period to incorporate the full effects of ESRD on
      survival and resource use. The effect of altering key variables was examined
      using 1-way sensitivity analyses. RESULTS: ESRD-related costs were significantly
      lower in patients receiving losartan-based treatment compared with those in the
      control group (savings per patient, 7390 [95% CI, 11,366-3414; P< 0.001] [1 = US 
      $1.75]). Incorporation of the cost of losartan into the assessment found reduced
      net costs (savings per patient, 6622 [95% CI, 10,591-2653; P= 0.001]). The
      projected mean number of life years saved due to ESRD risk reduction with
      losartan was 0.44 years (95% CI, 0.16-0.71; P = 0.002). Losartan treatment was
      found to save costs in all cases, even if the cost of renal replacement therapy
      for patients with ESRD was reduced by 50%. CONCLUSION: In this retrospective cost
      effectiveness analysis using data from the RENAAL study, losartan-based treatment
      for the prevention or delay of progression of diabetic nephropathy to ESRD in
      patients with DM-2 and nephropathy was found to be potentially cost saving
      compared with conventional anti-hypertensive therapy from the perspective of the
      UK NHS.

PMID- 24678071
TI  - Effects of the addition of high-dose vitamin C to polyethylene glycol solution
      for colonic cleansing: A pilot study in healthy volunteers.
AB  - BACKGROUND: Polyethylene glycol (PEG) solutions, with or without osmotic agents,
      are used to empty the large intestine before procedures such as colonoscopy or
      colonic surgery. Data concerning the effectiveness of vitamin C as an ingredient
      in colonic preparations are scant. OBJECTIVE: The aim of this article was to
      assess the effectiveness, acceptability, and tolerability of 6 preparations of a
      standard PEG electrolyte solution containing different doses of PEG, vitamin C
      (as an osmotic agent), and sodium sulfate in colonic cleansing. METHODS: This
      double-blind, randomized, 2-period crossover study was conducted at the
      Lariboisiere Hospital, Paris, France. Healthy adult volunteers were randomly
      assigned to receive 2 of 6 colonic cleansing preparations, each containing
      different doses of PEG (100 or 125 g/L), vitamin C (0, 5, or 10 g/L, in the form
      of sodium ascorbate, ascorbic acid, or a mixture of both), and sodium sulfate (5
      or 7.5 g/L), diluted in water to a volume of 2 L. Study drug administration was
      separated by a washout period of 7 to 15 days, after which the volunteers
      received an alternate preparation. Stools were collected for 10 hours after the
      start of solution ingestion. The primary efficacy end point was stool volume.
      Secondary end points included acceptability of taste, assessed using a 100-mm
      visual analog scale (VAS) (0 = excellent to 100 = execrable), taste criteria
      (saltiness, acidity, and sweetness, assessed on a 4-point Likert-type scale [0 =
      very pleasant to 3 = intolerable]) and tolerability (clinical effects [changes in
      body weight, blood pressure, heart rate, and nausea and vomiting] and biologic
      effects [changes in serum electrolytes, creatinine, hematocrit, and ascorbic
      acid]). RESULTS: Thirty volunteers (15 men, 15 women; mean [SD] age, 29.8 [8.2]
      years [range, 20-45 years]) were enrolled and completed the study. Mean (SD)
      stool volume obtained with preparations containing 10 g/L of vitamin C did not
      differ significantly from the volume obtained without vitamin C (2.54 [0.54] L vs
      1.93 [0.62] L; 95% CI, -0.13 to 1.47). Mean (SD) VAS scores for acceptability of
      taste ranged from 54.4 (25.0) (preparation E) to 74.4 (20.1) (preparation C) (P =
      0.03 preparation E vs all other preparations). The only significant difference in
      taste criteria was in acidity, with preparation A being the least acidic
      according to patients' ratings on the VAS (1.4 [0.7] vs 1.8 [0.4] [mean of the
      other 5 preparations combined]; P = 0.04 preparation A vs all other
      preparations). Mild dehydration occurred in 6 subjects (1 for each preparation).
      No clinical or biological adverse effects were found. CONCLUSIONS: In this study
      of 6 colonic cleansing preparations in healthy volunteers, the use of high-dose
      vitamin C as an osmotic agent in addition to PEG did not significantly increase
      stool output. All 6 preparations were well tolerated.

PMID- 24678072
TI  - Tolerability and feasibility of eptifibatide in acute coronary syndrome in
      patients at high risk for cardiovascular disease: A retrospective analysis.
AB  - BACKGROUND: Despite the beneficial effects of glycoprotein (GP) IIb/IIIa
      antagonists in patients with unstable angina and non-ST-segment elevation
      myocardial infarction (UA/NSTEMI), GP IIb/IIIa antagonists are rarely
      administered in general internal medicine wards in Israel, where most patients
      with UA/ NSTEMI are admitted, due to lack of adequate monitoring and safety
      concerns. OBJECTIVE: The aims of this study were to compare the prevalence of
      bleeding complications in patients with UA/NSTEMI receiving combination treatment
      with eptifibatide (a GP IIb/IIIa antagonist), the low-molecular-weight heparin
      enoxaparin, and acetylsalicylic acid (ASA) versus that in patients receiving
      enoxaparin and ASA in internal medicine wards in Israel, and to identify risk
      factors for bleeding complications. METHODS: This retrospective analysis included
      information from the database at Rambam Medical Center, Haifa, Israel. The
      database provided information from 4 of the 5 wards (the ward from which data
      were unavailable did not routinely use eptifibatide). Data were included from
      patients aged >=l.8 years who were admitted to the center with a diagnosis of
      UA/NSTEMI, were at high risk for death and/or nonfatal ischemic events based on
      American College of Cardiology/American Heart Association guidelines, were to
      undergo coronary intervention, and who had a Thrombosis in Myocardial Infarction
      risk score >=3 (moderate to high risk). Patients in the eptifibatide group
      received eptifibatide IV (180-MUg/kg bolus followed by a continuous infusion of 2
      MUg/kg . min up to 72 hours), enoxaparin SC (2 mg/kg . d), and ASA (100 mg/d).
      Patients in the control group received enoxaparin SC (2 mg/kg - d up to 96 hours)
      and ASA (100 mg/d). The prevalence of bleeding events was assessed using data up
      to 24 hours after the end of study drug administration. Major bleeding was
      defined as life-threatening bleeding at any site, intracranial hemorrhage, or
      bleeding accompanied by a decrease in plasma hemoglobin concentration of 5 g/dL
      or more. Otherwise, bleeding was considered minor. The risk for bleeding events
      was assessed using multivariate regression analysis. RESULTS: Data from 105
      patients (64 men, 41 women) were included in the analysis. In the eptifibatide
      and control groups, the mean (SD) ages were 68.7 (11.1) and 74.8 (11.0) years,
      respectively. These characteristics were statistically similar between the 2
      groups. The rates of major bleeding were similar between the eptifibatide and
      control groups (2 [3.8%] vs 0 patients). The rate of minor bleeding was
      significantly higher in the eptifibatide group compared with that in controls (11
      [21.2%] vs 4 [7.5%] patients; P = 0.03). The incidence of thrombocytopenia was
      statistically similar between the eptifibatide and control groups (0 vs 2 [3.8%]
      patients). The risk for bleeding was found to be associated with eptifibatide use
      (odds ratio, 4.8; 95% CI, 1.29-17.80), whereas an association with treatment was
      not found in the control group. CONCLUSION: The results of this retrospective
      analysis suggest that the risk for bleeding complications is higher with
      combination treatment with eptifibatide, enoxaparin, and ASA compared with that
      with enoxaparin and ASA in high-risk patients with UA/NSTEMI admitted to internal
      medicine wards in Israel.

PMID- 24678073
TI  - Open-label, randomized, controlled pilot study of the effects of a glucosamine
      complex on Low back pain.
AB  - BACKGROUND: A series of studies has suggested some efficacy of glucosamine in
      arthrosis of the knee, but virtually no documentation exists regarding its
      effects on low back pain. OBJECTIVES: The primary objective of this study was to
      examine whether a 12-week course of a glucosamine complex (GC) could benefit
      patients having low back pain despite a course of noninvasive physical therapy.
      In addition, we sought to delineate the subgroup of responders. METHODS: This
      open-label, randomized, controlled study was conducted at the Division of
      Rheumatology and Physical Medicine, Erasme University Hospital, Brussels,
      Belgium. Male and female outpatients aged 40 to 80 years with low back pain
      (duration, >= 12 weeks; pain score on 10-cm visual analog scale [VAS] [0 = none
      to 10 = worst imaginable], >=3 cm) despite noninvasive physical therapy (massage,
      stretching, heat application, and analgesics for >=4 weeks) were included.
      Patients were randomly assigned to receive, in addition to conventional treatment
      (CT) (physical therapy plus analgesics/antiinflammatories), a GC (enriched with
      sulfonyl methane, silicon, and a botanical extract of Ribes nigrum) or CT alone
      (control) for 12 weeks. Pain at rest and on movement (effort) and early morning
      lumbar stiffness were measured every 4 weeks using the VAS. The primary end point
      was improvement in VAS score for pain at rest at 12 weeks. Two validated
      questionnaires were used to assess improvements in quality of life (QOL)
      (Oswestry Disability Questionnaire [ODQ] [10 items; scale: 0 = no disability to
      60 = maximal disability] and Roland-Morris Disability Questionnaire [RMDQ] [24
      items; scale: 0 = no disability to 24 = severe disability]). Responders were
      defined as patients who positively assessed the efficacy of the GC. At each
      visit, patients were also asked about possible adverse events. RESULTS: Of 36
      enrolled patients, 32 completed the study (18 men, 14 women; mean [SE] age, 64
      [2] years; 17 in the GC group and 15 in the control group). Four patients were
      lost to follow-up. At week 4, changes from baseline VAS scores for pain at rest
      and lumbar stiffness were significantly greater in the GC group compared with the
      control group (P < 0.001 and P = 0.011, respectively). At week 4, QOL was found
      to be improved, as measured using the ODQ, in the GC group compared with the
      control group (P = 0.028), but the between-group difference as measured using the
      RMDQ was not significant. The improvements from baseline on the questionnaires
      were sustained over the 12-week period in the GC group (all, P < 0.001).
      Gastrointestinal adverse effects were reported by 1 GC-treated patient and 1
      patient in the control group, but neither patient withdrew from the study. Of the
      17 GC-treated patients, 9 considered themselves responders, but the profile of a
      responder could not be delineated. CONCLUSIONS: In this study in patients with
      low back pain, analgesic effect and improvement in QOL were found with the use of
      GC. GC was well tolerated.

PMID- 24678074
TI  - Clinical consequences of initial duloxetine dosing strategies: Comparison of 30
      and 60 mg QD starting doses.
AB  - BACKGROUND: To reduce the risk for treatment-emergent adverse events and increase
      patient compliance, clinicians frequently prescribe a suboptimal starting dose of
      antidepressants, with the goal of increasing the dose once the patient has
      demonstrated tolerability. OBJECTIVE: The aim of this study was to examine the
      tolerability and effectiveness associated with an initial week of duloxetine
      hydrochloride treatment at 30 mg QD and subsequent dose increase to 60 mg QD,
      compared with a starting dose of 60 mg QD. METHODS: In this open-label study, all
      patients met the criteria for major depressive disorder (MDD) described in the
      American Psychiatric Association's Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, Text Revision. Patients were required to wash out from
      previous antidepressant medications for 21 days, and were then randomized to
      receive duloxetine 30 or 60 mg QD for 1 week. After 1 week, patients receiving
      duloxetine 30 mg QD had their dose increased to 60 mg QD. Patients returned for
      assessments at weeks 2, 4, 6, 8, and 12. During the remainder of the 12-week
      study period, the duloxetine dose could be titrated based on the degree of
      response from 60 mg QD (minimum) to 120 mg QD (maximum), with 90 mg QD as an
      intermediate dose. Tolerability was assessed by means of discontinuation rates,
      spontaneously reported adverse events, changes in vital signs, and laboratory
      tests. Effectiveness measures included the 17-item Hamilton Rating Scale for
      Depression (HAMD17) total score, HAMD17 core and Maier subscales, individual
      HAMD17 items, the Hamilton Rating Scale for Anxiety total score, and the Clinical
      Global Impression of Severity. RESULTS: One hundred thirty-seven patients were
      enrolled (82 women, 55 men; mean age, 42 years; duloxetine 30 mg QD, 67 patients;
      duloxetine 60 mg QD, 70 patients). The rate of discontinuation due to adverse
      events did not differ significantly between patients starting duloxetine at 30 mg
      QD and 60 mg QD (13.4% vs 18.6%). The most frequently reported adverse events
      across both treatment groups were nausea, headache, dry mouth, insomnia, and
      diarrhea. In the first week of treatment, patients receiving duloxetine 30 mg QD
      had a significantly lower rate of nausea compared with patients receiving 60 mg
      QD (16.4% vs 32.9%; P = 0.03). Over the 12-week acute-treatment phase, patients
      starting duloxetine treatment at 30 mg QD had a significantly lower rate of
      nausea compared with patients initiating treatment at 60 mg QD (P = 0.047).
      Although between-group differences in the HAMD17 total score were not
      statistically significant at any visit, patients starting at 30 mg QD experienced
      significantly less improvement in HAMD17 core and Maier subscales at week 1
      compared with patients starting at 60 mg QD (core, P= 0.044; Maier, P = 0.047).
      After 2 weeks of treatment, the magnitude of improvement among patients starting
      at 30 mg QD did not differ significantly from that observed in patients who
      started treatment at 60 mg QD, and there were no significant between-group
      differences in effectiveness at any subsequent visit. CONCLUSIONS: Results from
      this open-label study in patients with MDD suggest that starting duloxetine
      treatment at 30 mg QD for 1 week, followed by escalation to 60 mg QD, might
      reduce the risk for treatment-emergent nausea in these patients while producing
      only a transitory impact on effectiveness compared with a starting dose of 60 mg
      QD.

PMID- 24678075
TI  - Comparison of preemptive analgesic effects of a single dose of nonopioid
      analgesics for pain management after ambulatory surgery: A prospective,
      randomized, single-blind studyin Turkish patients.
AB  - BACKGROUND: Preemptive analgesia used for postsurgical pain management has been
      shown to reduce the requirements of postoperative analgesics. OBJECTIVE: The aim
      of this study was to compare the preemptive analgesic effects of diflunisal,
      naproxen sodium, meloxicam, acetaminophen, and rofecoxin (no longer available in
      some markets) in patients undergoing ambulatory dental surgery and the need for
      postoperative pain management in these patients. METHODS: This prospective,
      randomized, single-blind study was conducted at the Departments of Anesthesiology
      and Reanimation and Oral and Maxillofacial Surgery, Baskent University, Adana
      Teaching and Medical Research Center, Adana, Turkey. Turkish outpatients aged >=
      16 years with American Society of Anesthesiologists physical status 1 (ie,
      healthy) and scheduled to undergo surgical extraction of an impacted third molar
      were enrolled. Patients were randomly assigned to receive diflunisal 500 mg,
      naproxen sodium 550 mg, meloxicam 7.5 mg, acetaminophen 500 mg, or rofecoxib 12.5
      mg. All medications were administered orally 1 hour before surgery as preemptive
      analgesia and after surgery if needed, up to the maximum recommended dose.
      Surgery was performed with the patient under local anesthesia (articaine
      hydrochloride). Pain intensity was assessed using a 100-mm visual analog scale
      (VAS) (0 = none to 100 = worst possible pain) at 2, 4, 6, and 12 hours after
      ambulatory surgery. The use of additional analgesics was recorded for 24 hours
      using patient diaries. Postoperative adverse events were recorded using the
      diaries. RESULTS: One hundred fifty patients (108 women, 42 men; mean [SE] age,
      26.8 [0.6] years; 30 patients per group) had data available for analysis.
      Demographic data were similar between the 5 groups. No significant differences in
      mean VAS scores were found between the 5 groups at any time point. All mean VAS
      scores indicated minor pain. The rate of additional postoperative analgesics
      required was significantly lower in the diflunisal group compared with groups
      receiving naproxen sodium, meloxicam, acetaminophen, and rofecoxib (3 [10%]
      patients vs 11 [37%], 15 [50%], 15 [50%], and 14 [47%] patients, respectively;
      all, P < 0.05). Bleeding at the surgical site was reported in 2 patients each in
      the diflunisal, naproxen sodium, meloxicam, and acetaminophen groups, and in 1
      patient in the rofecoxib group; the between-group differences were not
      significant. No significant differences in the prevalences of other adverse
      effects (eg, nausea, vomiting, allergy, gastrointestinal symptoms) were found
      between the 5 treatment groups. CONCLUSIONS: In the present study in patients
      undergoing third molar extraction, adequate preemptive analgesia, based on VAS
      scores, was found with all of the nonopioid analgesic agents used. Fewer patients
      required rescue medication with diflunisal. All 5 study drugs were similarly well
      tolerated.

PMID- 24678076
TI  - Effects of pentosan polysulfate in osteoarthritis of the knee: A randomized,
      double-blind, placebo-controlled pilot study.
AB  - BACKGROUND: Recent recommendations from the Group for the Respect of Excellence
      and Ethics in Science for the clinical assessment of the effects of disease
      modifying osteoarthritis (OA) drugs suggest that improvement in joint space
      narrowing, pain, and function relative to a control group should be the primary
      end points. OBJECTIVE: The aim of this study was to assess the ability of sodium
      pentosan polysulfate (NaPPS) to improve pain and function in patients with OA of
      the knee. METHODS: This randomized, double-blind, placebo-controlled pilot study
      was performed at the Queen Elizabeth II Medical Centre, Perth, Australia.
      Patients aged >=18 years with OA of the knee were randomly assigned to receive
      NaPPS 3 mg/kg or Ringer's solution (control), IM QW for 4 weeks. Efficacy was
      assessed at enrollment and weekly during the 4 weeks of treatment and at weeks 8,
      12, 16, and 24. Seven direct clinical assessments were made, including intensity
      of early morning joint stiffness, pain at rest, and pain on walking. A 10-cm
      visual analog scale (VAS) was used to assess pain at rest and on walking and
      early morning joint stiffness. Response was defined as a change from baseline in
      VAS score >=2 cm. Function was assessed using the 10-cm VAS to rate 13 activities
      of daily living (ADLs), including stair climbing and domestic chores. Patient
      global assessment of the overall effectiveness of the study drug comprised a 4
      point Likert scale (0 = not effective to 3 = maximally effective). An aggregate
      score for all ADL functions was calculated as the mean change from baseline score
      of all of the ADLs as determined at 4, 8, 12, 16, and 24 weeks after commencement
      of the study. For tolerability monitoring, hematology and biochemistry were used,
      and patients were questioned about adverse events at each visit. RESULTS: A total
      of 114 patients were enrolled (83 women, 31 men; mean [SD] age, 63.3 [1.5] years;
      NaPPS group, 54 patients; control group, 60 patients). Significant differences in
      scores of 3 of the 7 direct clinical assessments were found between the 2 groups
      (duration of joint stiffness at 4, 8, 12, and 16 weeks [all, P:5 0.015]; pain at
      rest at 8, 12, 16, and 24 weeks [all, P <= 0.017]; and patient global assessment
      at 4, 8, 12, 16, and 24 weeks [all, P <- 0.006]). The rates of trial continuation
      were higher in the NaPPS group compared with those in the control group at 8, 12,
      and 24 weeks (all, P < 0.05). Mean scores for 3 of 13 ADLs were significantly
      higher in the NaPPS group compared with those in the control group at weeks 8 and
      12 (all, P <= 0.03). On combining all of the ADL scores, functional improvement
      from baseline was found at weeks 8 and 12 in the NaPPS group (both, P = 0.02).
      Mild bruising at the injection site occurred in <1% of patients in both treatment
      groups. CONCLUSIONS: In this pilot study, 4 weekly injections of NaPPS were
      associated with significantly improved duration of joint stiffness and pain at
      rest compared with controls for 20 weeks after the cessation of treatment, and
      significantly improved pain on walking and overall function for 8 weeks after the
      cessation of treatment in these patients with OA of the knee.

PMID- 24678077
TI  - Carcinoma with shared pathologic characteristics of both hepatocellular carcinoma
      and cholangiocarcinoma.
AB  - BACKGROUND: alpha-Fetoprotein (AFP) is a useful marker of hepatocellular
      carcinoma (HCC), and protein induced by vitamin K absence or antagonist II (PIVKA
      II) and fucosylated AFP (AFP-L3) are specific tumor markers. OBJECTIVE: The aim
      of this article was to report a case of intrahepatic cholangiocarcinoma (CC) with
      high levels of expression of AFP, AFP-L3, and PIVKA-II. METHODS: A 70-year-old
      man weighing 66 kg with a diagnosis of intrahepatic CC presented with a liver
      tumor 4.0 cm in diameter and elevated concentrations of carbohydrate antigen 19-9
      (575 U/mL), PIVKA-II (379 mAU/mL), and AFP (497 ng/mL; AFP-L3, 88.1%). On
      extended medial hepatic segmentectomy, microscopy showed that the tumor was a CC
      without HCC. The patient subsequently underwent immunohistochemical assessments
      using cytokeratin-19, epithelial membrane antigen (EMA), hepatocyte paraffin-1
      (HP-1), PIVKA-II, and AFP. RESULTS: In all specimens, desmoplasia was observed.
      However, results of immunohistochemistry showed positive results for cytokeratin
      19 and EMA; HP-1 results were negative. Results of PIVKA-II and AFP testing in
      the tumor were positive. CONCLUSIONS: The case presented here showed
      characteristics of CC and HCC, whereas the histologic expression of the tumor
      suggested CC. Based on the literature search, this is the first known report of a
      case of a CC expressing AFP and PIVKA-II confirmed on immunohistochemical
      staining. This case is interesting with regard to the ability of the progenitor
      cells to differentiate HCC and CC.

PMID- 24678078
TI  - Effects of metabolic and myocardial microcirculatory abnormalities on the
      pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A
      prospective study in Japanese patients.
AB  - BACKGROUND: In diabetic patients, cardiac autonomic neuropathy is an important
      factor affecting prognosis. Whether this condition in diabetic patients is caused
      directly by neurovisceral metabolic disorder and/or indirectly by micro
      circulation remains to be clarified. OBJECTIVE: The aim of this study was to
      determine whether cardiac sympathetic nerve dysfunction can be detected using
      adenosine triphosphate (ATP) testing, while also investigating the effects of
      metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of
      cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM
      2) in Japan. METHODS: This prospective study was performed at the Division of
      Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital,
      Tokyo, Japan. Patients aged >= 18 years with DM-2 with no abnormalities on
      electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)
      201 myocardial scintigraphy test (ATP test) and iodine (I)-123
      metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered
      by continuous IV infusion over 6 minutes at 0.16 mg/kg . min. Five minutes after
      the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon
      emission computed tomography (SPECT) imaging was begun immediately after the end
      of ATP infusion and was completed 3 hours after stress to show washout from
      stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the
      front side and a SPECT image (early phase) was obtained 15 to 30 minutes later.
      After 3 hours, a planar image from the front side and a SPECT image (late phase)
      were obtained to show washout from stress to rest. The mean TI washout rate (ATP
      WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images
      and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The
      correlations of these measurements with the mean values of glycosylated
      hemoglobin (HbA1c) and fasting plasma glucose obtained from monthly measurements
      over the previous 6 and 24 months were determined. RESULTS: A total of 25
      patients were enrolled (13 men, 12 women; mean [SD] age, 59.86 [8.28] years).
      Significant negative correlations between both ATP-WR and MIBG-WR and HbA1c were
      found (r = -0.52 [P = 0.02] and -0.47 [P = 0.03], respectively). Although no
      correlation was found between ATP-WR values and the early phase H/M ratio, a
      significant positive correlation was observed between ATP-WR and H/M ratio (r =
      0.54; P = 0.02). CONCLUSIONS: In the present study in Japanese diabetic patients
      without subjective signs of coronary artery disease and without abnormalities on
      ECG or echocardiography, ATP-WR, an indicator of myocardial blood flow, was
      correlated with myocardial sympathetic nerve dysfunction and 24-month glycemic
      control. However, sympathetic nerve dysfunction was not correlated with 24-month
      glycemic control.

PMID- 24678079
TI  - Effects of oral fixed-dose combinations of telmisartan plus ramipril and losartan
      plus ramipril in hypertension: A multicenter, prospective, randomized, double
      blind, phase iii trial in adult indian patients.
AB  - BACKGROUND: A new oral fixed-dose combination (FDC) of telmisartan plus ramipril
      is being introduced in India for the treatment of patients with stage 2
      hypertension. OBJECTIVE: The aim of this study was to compare the effectiveness
      and tolerability of an oral FDC of telmisartan plus ramipril with those of an
      oral FDC of losartan plus ramipril in adult Indian patients with stage 2
      hypertension. METHODS: This multicenter, prospective, randomized, double-blind,
      Phase III study was conducted at 5 centers in India. Indian patients aged 18 to
      65 years with uncomplicated stage 2 essential hypertension (systolic/diastolic
      blood pressure [SBP/DBP], >160/>100 mm Hg) were enrolled. After a 2-week placebo
      run-in period, patients were randomly assigned to receive telmisartan 40 mg plus
      ramipril 5 mg (T + R) or losartan 50 mg plus ramipril 5 mg (L + R), PO (tablet)
      QD (before the morning meal) for 8 weeks. Supine blood pressure (BP) was measured
      at 0 (baseline) and 8 weeks of treatment. The primary end point was the mean
      reduction from baseline in BP. Responders were classified as patients who had a
      DBP <90 mm Hg at the end of 8 weeks of therapy. Tolerability was assessed using
      spontaneous reports of adverse events (AEs) during the follow-up visits and
      laboratory analyses performed at week 8. RESULTS: A total of 289 patients were
      enrolled (155 men, 134 women; mean age, 50.74 years). Of these, 8 patients in the
      T + R group and 7 in the L + R group were lost to follow-up and considered
      withdrawals. At the end of week 8, the mean percentage reduction in SBP was
      significantly greater in the T + R group compared with that in the L + R group
      (24.1% vs 19.4%; P < 0.05). The mean percentage reduction in DBP was also
      significantly greater in the T + R group compared with that in the L + R group
      (17.3% vs 12.5%; P < 0.05). The response rates in the T + R and L + R groups were
      statistically similar (79.1% vs 68.7%). The most common AEs in the T + R and L +
      R groups were cough (9 [6.1%] and 11 [7.8%] patients, respectively) and headache
      (7 [4.7%] and 8 [5.7%] patients, respectively). CONCLUSIONS: The results in this
      study in Indian patients with stage 2 essential hypertension suggest that the FDC
      of T + R controlled BP more effectively compared with the FDC of L + R over 8
      weeks. The response rates were similar between the 2 groups. Both treatments were
      well tolerated.

PMID- 24678081
TI  - Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic
      lesions in Japanese patients with coexisting hepatic disorders.
AB  - BACKGROUND: Many Japanese patients with hepatic disorders confirmed on diagnostic
      imaging and coexisting upper gastrointestinal (GI) peptic lesions receive
      treatment with proton pump inhibitors. Some pharmacotherapies used to treat
      peptic ulcers have been associated with adverse drug reactions (ADRs), including
      elevated liver enzyme levels. OBJECTIVE: The aim of this study was to determine
      the tolerability and effectiveness of rabeprazole sodium in treating peptic
      lesions in patients with coexisting hepatic disorders. METHODS: This open-label,
      practice-based, postmarketing surveillance investigation was conducted at 15
      centers across Japan. Male and female patients aged >=18 years with peptic
      lesions confirmed on upper GI endoscopy and with underlying hepatic disease were
      enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO
      (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using
      monitoring of the incidence of ADRs determined by direct patient questioning,
      spontaneous reporting, and laboratory assessment. All patients who received at
      least 1 dose of study drug were included in the tolerability assessment.
      Effectiveness was assessed at baseline and study end using the rates of
      achievement of improvement on endoscopy, relief of subjective/objective symptoms
      (rates of improvement in epigastric pain and heartburn), and global improvement.
      The effectiveness analysis included all patients with complete data before and
      after treatment. Subanalyses were conducted to determine the effectiveness of
      drug by identification of the proportion of patients with coexisting hepatic
      disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg,
      alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal
      ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement. RESULTS: A
      total of 114 patients were enrolled; 108 patients were included in the
      tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90
      patients; 20-mg dose, 18 patients) and 98 patients were included in the analysis
      of effectiveness. Twenty-one ADRs occurred in 11 (10.2%) patients. Serious ADRs
      occurred in 2 patients (elevated bilirubin level and hepatic encephalopathy, 1
      patient each). Administration of rabeprazole was discontinued in 5 patients due
      to the occurrence of the following ADRs: constipation (1 patient); epigastric
      pain (1); dyslalia, disorientation, tremor, sleep disorder, and hepatic
      encephalopathy (1); diarrhea (1); and elevated alkaline phosphatase and y
      glutamyl transpeptidase levels (1). On endoscopy, the proportion of patients
      achieving improvement with either dose was 30/33 (90.9%). The relief rates
      assessed using subjective symptoms were 47/55 (85.5%) and 47/56 (83.9%) for
      epigastric pain and heartburn, respectively. The proportion of patients achieving
      global improvement with either dose was 80/98 (81.6%) patients (49/62 [79.0%] for
      cirrhosis, 11/16 [68.8%] for chronic hepatitis, and 20/20 [100.0%] for other
      hepatic diseases [alcoholic hepatitis, fatty liver]). CONCLUSION: In this study
      in Japanese patients with hepatic disorders, rabeprazole was well tolerated and
      appeared effective for the treatment of upper GI peptic lesions.

PMID- 24678082
TI  - Effects of atorvastatin 10 mg/d on insulin resistance: A 12-week, open-label
      study in hyperlipidemic patients.
AB  - BACKGROUND: In addition to their cholesterol-lowering effects,
      hydroxymethylglutaryl coenzyme A reductase inhibitors ("statins") might have
      pleiotropic, nonlipid effects. Insulin resistance syndrome is known to increase
      the risk for cardiovascular disease. However, the effects of statins on insulin
      resistance are a subject of controversy. OBJECTIVE: We aimed to investigate the
      effects of atorvastatin on insulin resistance in hyperlipidemic patients.
      METHODS: This 12-week, prospective, nonrandomized, open-label study was conducted
      at the outpatient cardiology clinic, Ege University Medical School, Bornova
      Izmir, Turkey. Hyperlipidemic patients aged >=18 years with insulin resistance
      and no other components of the metabolic syndrome were included in the study.
      Atorvastatin 10 mg QD (after the evening meal) was administered by mouth (tablet)
      over a 12-week period. At baseline and after 12 weeks of treatment, insulin
      sensitivity was assessed using homeostasis model assessment (HOMA) index
      methodology. Serum lipid parameters and fasting levels of plasma glucose and
      insulin (FPG and FPI, respectively) were measured at the same 2 time points. The
      tolerability of atorvastatin was assessed using laboratory analysis and physical
      examination, including vital sign measurements. RESULTS: Fifteen white patients
      (9 women, 6 men; mean [SD] age, 52 [8] years) participated in the study. No
      significant changes in HOMA index were found (mean [SD], 3.1 [1.5] vs 3.2 [1.9]).
      The lipid profile was improved significantly at 12 weeks compared with baseline
      (mean [SD] low-density lipoprotein cholesterol, 173.2 [21.3] vs 110.8 [43.6]
      mg/dL; total cholesterol, 270.9 [21.5] vs 201.2 [46.7] mg/dL; and triglycerides,
      269.5 [46.3] vs 205.5 [49.3] mg/dL; all, P < 0.001). No significant change in
      mean (SD) plasma high-density lipoprotein cholesterol level (45.5 [6.6] vs 43.7
      [8.1] mg/dL) was found. In addition, no significant changes in FPG (85.3 [12.71
      vs 84.8 [10.4] mg/dL), or FPI (13.5 [9.7] vs 13.9 [10.1] MUU/mL) were found. None
      of the patients required withdrawal of medication due to an adverse event.
      CONCLUSION: In this pilot study in hyperlipidemic patients with insulin
      resistance, 12 weeks of treatment with atorvastatin 10 mg QD was effective in
      controlling hyperlipidemia but did not reduce the severity of insulin resistance.

PMID- 24678083
TI  - Mitoxantrone in worsening secondary progressive multiple sclerosis: A
      prospective, open-label study.
AB  - BACKGROUND: An antineoplastic agent, mitoxantrone (MX) is used to treat
      neurologic disability and/or reduce the frequency of clinical relapses in
      patients with secondary progressive, progressive relapsing, or worsening
      relapsing-remitting multiple sclerosis (MS). Based on a MEDLINE search for
      literature concerning the use of IV MX in patients with secondary progressive MS
      (SPMS), there is a paucity of data to identify the clinical characteristics of
      responders. OBJECTIVE: The aim of this study was to monitor the effects of IV MX
      in patients with SPMS and varied clinical characteristics whose condition
      continued to worsen despite receiving IV methylprednisolone treatment. METHODS:
      This prospective, open-label study was conducted at the Multiple Sclerosis
      Clinic, Center for Neurologic Disorders, Milwaukee, Wisconsin. Male and female
      patients aged >=18 years with SPMS whose neurologic condition, as assessed using
      routine neurologic examination, worsened despite at least one 5-day course of IV
      methylprednisolone treatment (1 g/d) were enrolled. Patients received
      premedication with an antiemetic and IV MX 12 mg/m(2) every 12 weeks for up to 2
      years, with a total cumulative dose not to exceed 96 mg/m(2). All patients were
      followed up for 1 year after treatment cessation. Efficacy was assessed at
      baseline, end of treatment, and 1-year follow-up using the Extended Disability
      Status Scale (EDSS) (which measures the functional disability level) (0 = normal
      findings on neurologic examination to 10 = death from MS complications).
      Tolerability was assessed before, during, and immediately after each infusion and
      at 2 weeks after each infusion, using direct questioning of, and spontaneous
      reporting by, the patients; physical examination; and laboratory assessments.
      Cardiac multigated acquisition scanning was performed at baseline and every 24
      weeks during the treatment period. RESULTS: Forty-eight patients were enrolled
      (28 women, 20 men; mean [SD] age, 47.6 [8.6] years; mean [SD] disease duration,
      12.5 [6.0] years; mean [SD] baseline EDSS score, 6.9 [1.2]). Twenty-three
      patients completed the entire course of treatment; the remaining 25 were
      withdrawn after 1 year of treatment due to lack of efficacy (22 patients),
      asymptomatic cardiac ejection fraction <40% (2), and severe septicemia and
      worsening of MS requiring extended respiratory support and hospitalization (1).
      Patients who completed only 1 year of treatment were younger compared with those
      who completed 2 years (mean age, 45.2 vs 50.1 years; P < 0.05). No significant
      change in mean EDSS score was found at the end of treatment or at 1-year
      posttreatment follow-up. In patients whose disability improved by 2-0.5 on the
      EDSS (11 patients at 1 year; 5 patients at 2 years), the degree of improvement
      noted at 1-year follow-up in patients with a baseline EDSS score 3.0 to 5.5
      versus 6.0 to 7.5 and 8.0 to 9.0 was significant (both, P < 0.05). Severe adverse
      effects occurred in 14.6% of patients and included marked leukopenia (peripheral
      white blood cell count, <100 cells/MUL) with urosepsis, requiring hospitalization
      in 7 patients, 1 of whom developed severe septicemia and worsening of MS,
      requiring >4 weeks of respiratory support. Cardiac ejection fraction decreased to
      <40% in 2 patients after 1 year of treatment (total dose, 48 mg/m(2)). These 2
      patients were asymptomatic, but the investigators decided to discontinue
      treatment. Cardiac function returned to normal range (but not to near-baseline
      levels) within 12 weeks after treatment cessation. Although all patients were
      premedicated with antiemetics, 10 (20.8%) reported mild nausea (treated with
      repeat administration of antiemetics), and 2 of 16 (12.5%) premenopausal patients
      reported slightly increased bleeding during menstruation after l year of IV MX
      therapy, requiring no medical therapy or adjustment in the treatment protocol.
      CONCLUSIONS: Based on the results of this study in this small group of patients
      with worsening SPMS, IV MX treatment for up to 2 years was not associated with a
      significant change in EDSS score at the conclusion of treatment or 1 year after
      treatment cessation.

PMID- 24678086
TI  - The Charles R. Ream, MD, award for excellence-2005.

PMID- 24678084
TI  - Prevalence of self-treatment with complementary products and therapies for weight
      loss: A randomized, cross-sectional Study in Overweight and Obese Patients in
      Colombia.
AB  - BACKGROUND: The use of complementary and alternative medicine for weight loss is
      becoming increasingly common worldwide. In overweight or obese patients, this
      practice could be harmful. Available data concerning the use of complementary
      therapies and products (CTPs) for weight loss in these patients in Colombia are
      limited. OBJECTIVES: The aims of this study were to determine the prevalence of
      self-treatment with CTPs in overweight or obese patients in Colombia and to
      explore the relationship between CTP use and demographic, anthropometric, and
      biochemical parameters. METHODS: This randomized, cross-sectional study was
      conducted at a registered dieticians' office located at the Center for
      Nutritional Care, School of Nutrition and Dietetics, University of Antioquia,
      Medellin, Colombia, and at an outpatient clinic attended by a registered
      dietician located at the Pablo Tobon Uribe Hospital, Medellin, Colombia. The
      study enrolled a random sample of overweight (body mass index [BMI], 25-30
      kg/m(2)) or obese (BMI, >30 kg/m(2)) male and female patients aged 20 to 50 years
      received nutritional treatment in Colombia in 2002. Data concerning the use of
      weight-loss CTPs were gathered, and their possible association with demographic,
      anthropometric, and biochemical data was explored. RESULTS: This randomized study
      comprised 94 patients (70 women, 24 men; mean [SD] age, 36.5 [9.7] years; mean
      [SD] BMI, 28.4 [4.2] kg/m(2)). Forty-nine (52.1%) patients reported self
      treatment with weight-loss CTPs; 40 (42.6%) patients used complementary products,
      and 21 (22.3%) used complementary therapies. Among the products, inadequately
      identified herbal medicines (ie, absence of available information concerning the
      composition of the products or information could not be obtained from the patient
      [many of the products used were not authorized for distribution in Colombia]),
      folkloric or home remedies, and commercial diets were most commonly used (40.0%,
      40.0%, and 27.5%, respectively). The use of CTPs was more prevalent in women
      compared with men (P < 0.001; odds ratio [OR] = 6.43). In women, CTP use was
      significantly higher in patients with a higher educational level (P = 0.008; OR =
      3.82) and in those who were single (P = 0.038; OR = 2.97). The use of CTPs was
      also more frequent in patients with a negative view of their current nutritional
      therapy (P = 0.002; OR = 6.8). CONCLUSIONS: In the small group of overweight and
      obese patients in this study, 52.1% used CTPs. In obese women, those with a
      higher educational level and/or who were single were more likely to use CTPs.
      Patients were also more likely to use CTPs if they had a negative view of their
      current nutritional therapy.

PMID- 24678087
TI  - Effects of gliclazide dose escalation on postprandial hyperglycemia in type 2
      diabetes mellitus: A prospective, open-label, case-controlled, dose-escalation
      study.
AB  - OBJECTIVES: The aims of this study were to determine the effects of increasing
      doses of gliclazide on postprandial glucose excursions after a standardized
      breakfast and lunch, and to clarify the relationship between gliclazide dose and
      glucose response. METHODS: This prospective, open-label, case-controlled, dose
      escalation study was conducted at the Addington Hospital Diabetes Clinic,
      eThekwini/Durban, KwaZulu-Natal, South Africa. Male and female patients aged >=18
      years with type 2 diabetes mellitus (DM) and postprandial hyperglycemia (2-hour
      postprandial blood glucose [PPBG2 h] level, >=11.1 mmol/L [>=200 mg/dL]) and
      receiving an oral hypoglycemic agent were eligible. After a 1-week washout period
      during which patients were asked to discontinue treatment with all oral
      hypoglycemic agents, baseline glycemic measurements were performed (fasting blood
      glucose, PPBG2 h, 6-hour postprandial blood glucose [PPBG6 h], mean blood glucose
      [MBG], plasma insulin, fasting serum fructosamine, and glycosylated hemoglobin).
      All patients subsequently received 2 weeks of oral treatment with each of 3 doses
      of gliclazide: 40, 80, and 160 mg/d. Glycemic parameters were measured at the end
      of each dosing interval. Adverse-effect monitoring included direct reporting of
      untoward effects to the resident medical practitioner, clinical examination,
      monitoring of home blood glucose records, hematology, and liver and kidney
      function tests. Compliance was assessed using pill counts, examination of diary
      entries, and patient interview. RESULTS: Thirty-three patients were screened; 14
      entered the dose-escalation phase. Thirteen patients completed the study (7
      women, 6 men; mean [SD] age, 52.0 [11.1] years); 1 was withdrawn because of poor
      compliance. Dose escalation from 40 to 80 mg/d was associated with a significant
      change only in MBG (mean [SD], 11.3 [4.2] vs 10.0 [3.9] mmol/L [203.6 (75.7) vs
      180.1 (70.3) mg/dL]; P<0.001). Dose escalation from 80 to 160 mg/d was associated
      with a significant change only in PPBG6 h (9.5 [4.2] vs 10.3 [4.1] mmol/L [171.1
      (75.7) vs 185.6 (73.9) mg/dL]; P=0.018). No other significant changes in glycemic
      parameters between doses were found throughout the treatment period. No adverse
      effects were reported. CONCLUSIONS: In this small study of gliclazide dose
      escalation in patients with type 2 DM and postprandial hyperglycemia, gliclazide
      80 mg/d was associated with a reduction in postprandial hyperglycemia. Dose
      escalation from 80 to 160 mg/d was not found to be associated with additional
      clinical benefit. Based on these results, we recommend that gliclazide dose
      escalation to the maximum dose recommended by the manufacturer be guided by
      measures of glycemia. All doses were well tolerated.

PMID- 24678088
TI  - Estimation of minimum whole-blood tacrolimus concentration for therapeutic drug
      monitoring with plasma prednisolone concentration: A retrospective cohort study
      in Japanese kidney transplant recipients.
AB  - BACKGROUND: In immunosuppressive therapy administered after organ
      transplantation, therapeutic drug monitoring (TDM) of tacrolimus must be
      performed frequently because of the large variation in its pharmacokinetic
      properties and a progressive decrease in dose requirements. An indicator for
      estimating the target minimum whole-blood tacrolimus concentration (Cmin TAC)
      would be useful to minimize the number of blood samplings required for tacrolimus
      TDM. OBJECTIVES: The primary objective of this study was to investigate whether
      plasma prednisolone concentration, postoperative days (POD) and AUC 0 to 9 hours
      before transplantation (AUC0-9int) are useful indicators of tacrolimus TDM. The
      secondary objective was to determine the usefulness of blood tacrolimus
      concentration as an indicator of the development of nontraumatic, glucocorticoid
      induced necrosis of the femoral head, an adverse event that has been associated
      with the use of prednisolone in vivo. METHODS: This open-label, nonrandomized,
      retrospective study was conducted at the Department of Transplantation and
      Regenerative Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
      Data from 43 male and 22 female patients (mean age, 38 years [range, 9-64 years])
      who received a living-related kidney transplant from 2001 to 2004 were included.
      Multiple blood samplings were performed to determine AUC0-9int, AUC 0 to 9 hours
      after drug administration and after transplantation (AUC0-9), Cmin TAC, Cmax, and
      Tmax after transplantation. The correlations between each parameter were
      determined. The correlation between POD and the changes in tacrolimus
      bioavailability was investigated using the indicator, defined as the tacrolimus
      dose required to maintain the target (10-15 ng/mL) Cmin TAC (dose/C10-15).
      Correlations between dose/C10-15 and AUC0-9int (3 AUC0-9int groups, defined as
      follows: low, medium, and high [<93, ?93-<=152, and ?152 ng.h/mL, respectively])
      were determined. Correlations between mean Cmin values of prednisolone at a dose
      of 40 mg on PODs 4 to 11 (Cmin PSL40) and Cmin TAC, or AUC0-9int were determined.
      A subanalysis was used to determine the relationship between dose/C10-15 and the
      prevalence of nontraumatic, glucocorticoid-induced necrosis of the femoral head.
      RESULTS: Cmin TAC was found to be significantly correlated with AUC0-9int
      (r=0.554; P<0.001) and Cmin PSL40 (r=0.336; P<0.001). In the low-AUC0-9int group,
      dose/C10-15 was higher than that of the other groups (P<0.001). AUC0-9int was
      significantly correlated with Cmin PSL40 (r=0.445; P<0.001)). Dose/C10-15 in the
      patient group that had necrosis of the femoral head was lower than that of the
      group without necrosis (n=6; P<0.01). CONCLUSIONS: The results of this small,
      retrospective study suggest that Cmin PSL40, AUC0-9int, and POD were significant
      predictors of Cmin TAC. These parameters were found to be a useful indicator of
      tacrolimus TDM in these Japanese transplant recipients. Our results also suggest
      that dose/C10-15 and AUC0-9int might be useful indicators for estimating the risk
      for nontraumatic, steroid-induced necrosis of the femoral head. (Curr Ther Res
      Clin Exp. 2006;67: 103-117) Copyright (c) 2006 Excerpta Medica, Inc.

PMID- 24678089
TI  - Effects of vitamins E and C supplementation on hepatic glutathione peroxidase
      activity and tissue injury associated with ethanol ingestion in malnourished
      rats.
AB  - BACKGROUND: Oxidative stress has been associated with tissue injury in alcoholic
      liver disease. Although this close association is well known, whether prevention
      of oxidative stress retards tissue injury has not been thoroughly investigated.
      OBJECTIVE: The aim of this study was to determine the effects of supplementation
      with vitamins E and C on antioxidant enzyme status and histologic changes in
      hepatic tissue in a rat model of alcoholic liver disease. METHODS: This 8-week,
      blinded, controlled study was conducted at the Department of Internal Medicine,
      Trakya University, Edirne, Turkey. Weanling albino female protein-deficient
      Wistar rats weighing ~200 g were randomly assigned to 1 of 6 groups: (1) liquid
      diet+ethanol+vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet+ethanol+vitamin C
      10 mg/kg PO (LDetvitC); (3) liquid diet+ethanol+vitamin E 15 mg/kg+vitamin C 10
      mg/kg PO (LDetvitEC); (4) liquid diet+ethanol (LDet); (5) liquid diet+isocaloric
      sucrose (LDS); and (6) normal diet (control). The primary end point of the study
      was to determine whether antioxidant vitamin E/C combination therapy prevents
      development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After
      being euthanized at week 8, the rats were weighed, and their livers and spleens
      were weighed. Hepatic tissue specimens were histopathologically assessed
      according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide
      dismutase, and catalase activities were determined. Biochemical tissue collagen
      concentrations were measured to determine the presence of hepatic fibrosis.
      RESULTS: Seventy-two rats were included in the study (mean [SE] weight, 205 [21]
      g) (12 rats per group). Initially planned to last 48 weeks, the study was
      terminated at 8 weeks due to the death of 3 rats in each group (except the LDS
      group and control group). The relative liver weight was significantly lower in
      the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%]
      vs 4.8% [0.9%]; P<0.01). Mean (SE) hepatic tissue glutathione peroxidase activity
      was significantly reduced in the LDet-treated rats compared with controls (1.2
      [0.2] vs 2.6 [0.3] U/mg protein; P<0.001). The groups that received
      supplementation with vitamin E, vitamin C, and vitamins E and C combined had
      significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5],
      2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group
      (1.2 [0.2] U/mg protein) (all, P<0.001). No significant between-group differences
      in hepatic superoxide dismutase or catalase activities were found. Compared with
      controls (14.5 [1.9] MUg collagen/mg protein), the mean (SE) histologic hepatic
      collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5
      [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] MUg collagen/mg protein in the
      LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P<0.01,
      P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Compared with the LDet
      group, the mean hepatic collagen concentration was significantly lower in the
      LDetvitE, LDetvitC, and LDetvitEC groups (P<0.01, P<0.05, and P<0.01,
      respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic
      inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P<0.05).
      The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score
      compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P<0.05).
      CONCLUSIONS: The results of this study in protein-deficient rats fed with a high
      fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a
      combination of vitamins E and C was associated with decreased ethanol-induced
      hepatic glutathione peroxidase activity and hepatic fibrosis, and that
      supplementation with vitamins E and C might have attenuated the development of
      hepatomegaly and hepatic necroinflammation, whereas this result was not found in
      the group given a liquid diet and ethanol in this 8-week study. (Curr Ther Res
      Clin Exp. 2006;67:118-137) Copyright (c) 2006 Excerpta Medica, Inc.

PMID- 24678090
TI  - Antitumor and immunomodulatory effects of weikangfu granule compound in tumor
      bearing mice.
AB  - BACKGROUND: Weikangfu granule compound (WKC) is a drug preparation based on a
      clinical prescription drug, Weikangfu-tang, which has been found to have
      therapeutic effects on gastric cancer. WKC comprises 7 components, including
      polysaccharides, saponin, flavonoids, and essential oil. OBJECTIVE: The purpose
      of this study was to assess the antitumor and immunomodulatory effects of WKC in
      a tumor-bearing rodent model. METHODS: Male and female Kuming mice weighing ~20 g
      were subcutaneously implanted with sarcoma 180 (S180) tumor cells and randomly
      assigned to 1 of 5 treatment groups: oral WKC 175, 350, or 525 mg/kg.d, isotonic
      saline (negative control), or intraperitoneal cyclophosphamide 25 mg/kg.d
      (positive control). All treatments were administered daily for 10 days. After
      euthanization on day 11, the mice, tumors, and spleens were weighed. Lymphocyte
      proliferation and cytotoxic T lymphocyte (CTL) activity were determined using the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cellular viability
      assay method. Macrophage phagocytosis was identified using a yeast test. RESULTS:
      Fifty mice were included in the study (10 mice were assigned to each group). The
      tumors of the mice administered WKC 175, 350, and 525 mg/kg.d were significantly
      regressed, as determined using MICs, compared with those in the negative-control
      group (P<0.05, P<0.01, and P<0.01, respectively), and the inhibitory rates were
      30.43%, 46.72%, and 54.35%, respectively. Compared with those in the negative
      control group, CTL activities and lymphocyte proliferations in the presence of
      concanavalin A were significantly greater in the WKC-treated groups at all doses
      (CTL activities: P<0.05, P<0.01, and P<0.01, respectively; lymphocyte
      proliferations: P<0.05, P<0.01, and P<0.01, respectively). In the groups
      receiving WKC 175, 350, and 525 mg/kg.d, the phagocytic rates were 1.5- to 2.0
      fold those in the negative-control group (P<0.05, P<0.01, and P<0.01,
      respectively). In the groups receiving WKC 175, 350, and 525 mg/kg.d, the
      phagocytic indexes were 3.7- to 5.0-fold those in the negative-control group
      (all, P<0.01). In contrast, lymphocyte proliferation in the positive-control
      group was significantly less compared with that in the negative-control group
      (P<0.01), but no significant differences were found in CTL activities or
      macrophage phagocytosis between these 2 groups. CONCLUSION: The results of this
      study in a rodent model suggest that WKC exhibited antitumor and immunomodulatory
      activities in S180-bearing mice, and that WKC improved nonspecific and specific
      immune functions in mice, such as lymphocyte proliferation, CTL activity, and
      macrophage phagocytosis.

PMID- 24678091
TI  - Comparison of two amoxicillin/clavulanic acid-resistant profiles employing two
      types of assay disks: A pilot study in 50 isolates from a tertiary care hospital
      in India.
AB  - BACKGROUND: During a period from January to March 2005, there was a sudden 3.85
      fold increase in isolates with in vitro resistance to amoxicillin/clavulanic acid
      at Sant Parmanand Hospital, a private tertiary care hospital in Delhi, India,
      without an increase in treatment failures. OBJECTIVE: This pilot study was
      designed to assess whether 2 different brands (one exclusively used during the
      last quarter of 2004, one exclusively used during the first quarter of 2005) of
      antibiotic disks used at the hospital were related to the reported change in
      resistance pattern. METHODS: During April 2005, 50 consecutive hospital isolates,
      45 gram negative and 5 gram positive, were tested in parallel, employing 2 brands
      of amoxicillin/clavulanic acid disks: HiMedia disks (HiMedia Laboratories,
      Mumbai, India) and BBL(TM) Sensi-Disc(TM) Antimicrobial Susceptibility Test Discs
      (BD Diagnostic Systems, Sparks, Maryland). RESULTS: Of 50 consecutive hospital
      isolates tested with the HiMedia disks, 40 were resistant and 10 were
      susceptible. Of those tested with the BBL disks, 10 were resistant and 40 were
      susceptible. The susceptibility profiles observed were significantly different
      (P<0.001). CONCLUSION: In this study, significantly different susceptibility
      results were found when 2 different brands of antibiotic disks were used to test
      the amoxicillin/clavulanic susceptibility of 50 consecutive isolates in this
      private hospital in India.

PMID- 24678093
TI  - Effects of orlistat plus diet on postprandial lipemia and brachial artery
      reactivity in normolipidemic, obese women with normal glucose tolerance: A
      prospective, randomized, controlled Study.
AB  - BACKGROUND: Postprandial lipemia (PPL) is an independent predictor of
      earlyatherosclerosis and coronary artery disease. It is defined as a postprandial
      triglyceride (TG) level >=80% higher than the fasting level. Brachial arterial
      reactivity (BAR) is used to identify early-phase atherosclerosis. Data concerning
      whether orlistat improves PPL and endothelial function are lacking. OBJECTIVE:
      The aim of this study was to determine the effects of orlistat on PPL and BAR in
      normolipidemic, obese women with normal glucose tolerance. METHODS: This
      prospective, randomized, controlled study was conducted at Baskent University,
      Ankara, Turkey. Normolipidemic, obese women aged 18 to 65 years with normal
      glucose tolerance were eligible for screening. On screening, demographic
      information, anthropomorphic parameters (body mass index [BMI], waist
      circumference [WC], hip circumference, waist-hip ratio), BAR, laboratory test
      results (level of insulin resistance assessed using the homeostasis model
      assessment-insulin resistance [HOMA-IR] index, serum lipid profile, fasting
      plasma levels of glucose and insulin [FPI]), and oral fat-loading test results
      were recorded as baseline values. The primary end points were the effects of
      orlistat + diet on PPL (assessed using the AUC of TG) and BAR. Women found on
      screening to be PPL positive were randomly assigned in a 2:1 ratio to treatment
      with orlistat 120 mg TID plus low-calorie diet (600-kcal/d deficit; minimum, 1200
      kcal/d) or low-calorie diet only (control) for 12 weeks. After 12 weeks, all of
      the above assessments were repeated, and AUC values for lipid parameters were
      calculated as secondary outcome measures. To assess tolerability and compliance,
      women were monitored by telephone each week and instructed to return every 4
      weeks for clinic visits. RESULTS: Twenty-seven women were identified as PPL
      positive and assigned to the orlistat + diet group (18 subjects) or the control
      group (9) (mean [SD] age, 45.9 [2.3] years; mean [SD] weight, 87.4 [2.5] kg; mean
      [SD] BMI, 36.0 [0.8] kg/m(2)). Treatment with orlistat + diet was associated with
      significantly greater changes from baseline compared with controls in WC (P=
      0.003), fasting and postprandial serum TG levels (P = 0.012 and P < 0.001,
      respectively), FPI level (P = 0.001), and HOMA-IR index (P < 0.001). Logistic
      regression analysis found that 12 weeks of treatment with orlistat + diet was
      associated with a numeric, but statistically non-significant, 4.1-fold change in
      PPL, which was independent of reductions from baseline in weight and WC. Neither
      treatment was associated with significant changes from baseline in BAR. The
      prevalences of gastrointestinal symptoms previously found to be related to
      orlistat use were statistically similar between the orlistat + diet and control
      groups (9 [50.0%] vs 3 [33.3%] subjects). CONCLUSIONS: The results of this small
      study in normolipidemic, obesewomen with normal glucose tolerance suggest that 12
      weeks of treatment with orlistat 120 mg/d plus low-calorie diet was associated
      with a numeric, but statistically nonsignificant, 4.1-fold change from baseline
      in PPL, which was independent of reductions from baseline in weight and WC.
      Treatment with orlistat + diet was associated with significant effects on WC, TG,
      and level of insulin resistance, but not BAR.

PMID- 24678094
TI  - Effects of combination treatment with policosanol and omega-3 fatty acids on
      platelet aggregation: A randomized, double-blind clinical study.
AB  - BACKGROUND: Policosanol is a mixture of long-chain primary aliphatic
      alcoholspurified from sugar cane wax that has cholesterol lowering and
      antiplatelet effects. Omega-3 fatty acids (FA) have triglyceride lowering and
      antiplatelet effects. Combination treatment with policosanol and omega-3 FA
      (Omega23FA) has been associated with significant inhibition of platelet
      aggregation in rabbits compared with either drug alone. OBJECTIVE: The aim of
      this study was to investigate the effects of combination treatment with Omega3FA
      (1 g/d) and policosanol (Omega3FA+Poli) compared with Omega3FA (1 g/d) plus
      placebo (Omega3FA+Pla) on platelet aggregation in human patients with
      hypercholesterolemia. METHODS: This randomized, double-blind, clinical study at
      the Surgical Medical Research Center (Havana City, Cuba) recruited outpatients
      from lipid clinics, with some atherosclerotic risk factors. Outpatients of both
      sexes aged 20 to 75 years with serum total cholesterol (TC) levels >=5 and <6
      mmol/L were eligible to enroll. They were included in the study at the end of a 4
      week diet stabilization period if their platelet aggregation to arachidonic acid
      (AA) was >=50% and serum TC level remained >=5 mmol/L. Patients were then evenly
      randomized to receive Omega3FA (1 g/d) + placebo or Omega3FA (1 g/d) +
      policosanol (10 mg/d) to be taken PO with the evening meal for 21 days. Treatment
      was assigned according to a randomization code using balanced blocks and a 1:1
      allocation ratio. Inhibition of platelet aggregation to AA was the primary
      efficacy variable, while effects on platelet aggregation to collagen and
      epinephrine and on lipid profile were secondary variables. Drug compliance and
      adverse events (AEs) were monitored. Tolerability was assessed using physical
      examinations and laboratory test results. RESULTS: Sixty-four subjects were
      initially enrolled. Fifty-four patients (30 women, 24 men; mean [SD] age, 58.4
      [12] years, [range, 40-70 years]) met the inclusion criteria and were randomized
      to treatment; 2 groups of 27. After 21 days, platelet aggregation to AA was
      significantly inhibited in the 2 groups. Omega3FA+Poli inhibited platelet
      aggregation to all agonists by >=20%. Platelet aggregation to AA 1.0 and 1.5 mM
      was inhibited with combination treatment (39.6% and 33.9%, respectively; both P <
      0.001 vs baseline; P < 0.001 and P < 0.01, respectively, vs Omega3FA+Pla) and
      with Omega3FA+Pla (11.0% and 13.3%; both, P < 0.001). Combination treatment was
      more effective in inhibiting platelet aggregation to AA 1.0 and 1.5 mM in 28.6%
      (P < 0.001) and 20.6% (P < 0.01), respectively. Platelet aggregation to collagen
      1 MUg/mL was significantly inhibited with combination treatment and with
      Omega3FA+Pla compared with baseline (43.2% and 15.1%, respectively; both, P <
      0.001), but the effects of combination treatment were significantly greater (P <
      0.01). Platelet aggregation to epinephrine 0.1 mM was inhibited with
      Omega3FA+Poli and Omega3FA+Pla (34.8% and 20.1%; both, P < 0.001), with similar
      results for both groups. Bleeding time did not change significantly for either
      group and Omega3FA+Pla did not significantly change the lipid profile.
      Combination treatment did significantly reduce levels of low-density lipoprotein
      cholesterol (LDL-C) (17.4%; P < 0.001 vs baseline, P < 0.05 vs Omega3FA+Pla) and
      TC (10.1%; P < 0.001 vs baseline, P < 0.05 vs Omega3FA+Pla), increase high
      density lipoprotein cholesterol (HDL-C) levels (18.0%; P < 0.001 vs baseline),
      but did not significantly change triglyceride levels. Three patients (2 from the
      Omega3FA+Poli group and 1 from the Omega3FA+Pla group) withdrew from the trial,
      though none were due to AEs. Two patients receiving combination treatment
      reported mild AEs (headache). All treatments were well tolerated. CONCLUSIONS: In
      these patients, policosanol (10 mg/d) administered concomitantly with Omega3FA (1
      g/d) enhanced the inhibition of platelet aggregation to AA and collagen, but not
      to epinephrine, compared with Omega3FA+Pla, without significantly affecting
      bleeding time. Concomitant treatment was also associated with reduced levels of
      LDL-C and TC and raised HDL-C levels. All treatments were well tolerated.

PMID- 24678095
TI  - Pharmacokinetics of experimental pentavalent antimony after intramuscular
      administration in adult volunteers.
AB  - BACKGROUND: Pentavalent antimony (SbV) has demonstrated therapeuticeffectiveness
      against clinical manifestations of leishmaniasis, an infection caused by
      Leishmania, a genus of flagellate protozoa comprising parasites of worldwide
      distribution. Approximately 1.8 million new cases are reported annually.
      OBJECTIVE: The aim of this study was to assess the pharmacokinetics of the
      investigational generic SbV, Ulamina (pentachloride of antimony + N
      methylglucamine), in healthy adult volunteers. METHODS: In this study, SbV was
      administered IM as a single 5-mg/kg dose.Blood samples were collected at 0.25,
      0.75, 1, 2, 4, 8, 12, and 24 hours after administration; urine samples were
      collected at 6-hour intervals during the 24-hour postadministration period.
      Determination of trivalent antimony, SbV, and total antimony concentrations in
      blood and urine samples was carried out using atomic absorption spectrometry.
      Clinical history was reviewed and the subjects were monitored before and after
      administration of SbV using physical examination, weight, and hepatic- and renal
      function studies. The pharmacokinetic parameters calculated were Cmax, Tmax,
      absorption constant (Ka), elimination constant (Kel), AUC2-24h, AUC0-infinity,
      elimination phase (t1/2beta), volume of distribution (Vd), and urinary excretion
      rate. RESULTS: Five subjects (3 men, 2 women; mean age, 28 years [range, 18-34
      years]) were included in the study. One hour after drug administration the
      following values were obtained: Cmax, 1.1 MUg/mL; Tmax, 1.3 hours; Ka, 1.87
      hours; Kel, 0.043 hours; AUC0-24h, 12.26 MUg/mL . h; AUC0-infinity, 19.84 MUg/mL
      . h; t1/2beta, 17.45 hours; Vd, 6.6 L/kg; and urinary excretion rate, 2.8 MUg/h;
      these were mean values for the entire study group. The single dose was well
      tolerated by all subjects. CONCLUSIONS: The investigational generic SbV, Ulamina,
      was associated with linearelimination after IM administration of a single 5-mg/kg
      dose. A 2-compartment pharmacokinetic model was observed in these volunteers; the
      mean t1/2beta, was 17.45 hours and the mean Vd was 6.6 L/kg.

PMID- 24678096
TI  - Olprinone/dopamine combination for improving diaphragmatic fatigue in
      pentobarbital-anesthetized dogs.
AB  - BACKGROUND: Diaphragmatic fatigue might contribute to the development of
      respiratory failure. In particular, the spontaneous, natural rate of phrenic
      nerve discharge occurs mainly in low-frequency ranges making low-frequency
      fatigue clinically important in both humans and animals. Olprinone, a
      phosphodiesterase 3 inhibitor, improves contractility in fatigued diaphragm, but
      is also associated with hypotension. Dopamine might be used concomitantly for
      treating related hypotension. OBJECTIVE: The purpose of the study was to assess
      the effect of olprinoneplus dopamine on diaphragmatic fatigue in pentobarbital
      anesthetized dogs. METHODS: This nonblinded study was conducted at the Department
      ofAnesthesiology, Institute of Clinical Medicine, Tsukuba, Japan. Diaphragmatic
      fatigue (assessed by a decrease in diaphragmatic contractility) was induced by
      intermittent supramaximal bilateral electrophrenic stimulation at a frequency of
      20 Hz applied for 30 minutes. Immediately after the fatigue-producing period,
      groups 2, 3, and 4 received an initial 10 MUg/kg dose of olprinone. Group 2 then
      received maintenance olprinone of 0.3 MUg/kg . min; group 3 received maintenance
      olprinone 0.3 MUg/kg . min plus dopamine 2 MUg/kg . min; and group 4 received
      maintenance olprinone 0.3 MUg/kg . min plus dopamine 5 MUg/kg . min. Group 1
      received no study drug. Olprinone and dopamine were administered IV for 30
      minutes. Diaphragmatic contractility was assessed by measuring the maximal
      transdiaphragmatic pressure (Pdi) generated by test stimuli after airway
      occlusion at functional residual capacity. Hypotension induced by the study drugs
      was defined as a >10 mm Hg decrease in mean arterial pressure (MAP), calculated
      by diastolic pressure plus 1/3 pulse pressure, from baseline. RESULTS: Twenty
      eight mongrel dogs (18 males and 10 females, weighing 10-15 kg)were used in the
      study; 7 dogs were randomly assigned to each treatment group. When fatigue was
      established in each group, mean (SD) Pdi at low-frequency (20 Hz) stimulation
      decreased significantly from baseline in all groups (group 1: 15.6 [2.2] vs 11.7
      [2.4] cm H2O, P = 0.008; group 2: 15.4 [1.5] vs 11.6 [1.3] cm H2O, P= 0.005;
      group 3:15.5 [2.0] vs 11.6 [1.8] cm H2O, P= 0.006; group 4: 15.7 [1.4] vs 12.0
      [1.4] cm H2O, P= 0.008), while no significant change existed in Pdi at high
      frequency (100 Hz) stimulation (P = NS). After study drug administration, Pdi in
      groups 2, 3, and 4 increased significantly from fatigued values at both 20 Hz
      stimulation (group 2: 11.6 [1.3] vs 21.8 [2.0] cm H2O, P = 0.001; group 3: 11.6
      [1.8] vs 22.2 [1.8] cm H2O, P = 0.001; group 4: 12.0 [1.4] vs 25.9 [1.9 ] cm H2O,
      P = 0.001) and 100 Hz stimulation (group 2: 22.0 [2.2] vs 29.0 [1.9] cm H2O, P =
      0.002; group 3: 22.1 [2.0] vs 29.3 [2.2] cm H2O, P = 0.002; group 4: 21.8 [2.2]
      vs 31.7 [2.4] cm H2O, P= 0.001). The increase in Pdi was significantly larger in
      group 4 compared with the other 3 groups (all, P < 0.05). Hypotension was not
      observed in group 4. MAP did not change significantly in group 1 or group 4
      compared with baseline or fatigued MAP values (P = NS). Groups 2 and 3 had
      significant decreases in MAP with treatment compared with values in group 1 and
      with baseline and fatigued MAP values (all, P < 0.05). The MAP of group 4 was
      significantly greater than the MAP of groups 2 and 3 with treatment (both, P <
      0.05). CONCLUSIONS: Olprinone 0.3 MUg/kg sd min plus dopamine 5 MUg/kg . min
      improved contractility in fatigued diaphragms and was not associated with
      hypotension in these pentobarbital-anesthetized dogs. Olprinone monotherapy and
      olprinone 0.3 MUg/kg . min plus dopamine 2 MUg/kg . min might improve
      contractility significantly. However, it was also associated with significant
      decreases in MAP.

PMID- 24678098
TI  - Announcing trials from resource-limited settings.

PMID- 24678097
TI  - Effect of perinatal factors on time of first stool passage in preterm newborns:
      An open, prospective study.
AB  - BACKGROUND: Delayed passage of first stool by a newborn after birth might be an
      initial sign of clinical problems, such as meconium ileus, meconium plug
      syndrome, and intestinal atresia. Successful treatment of these conditions
      depends on early diagnosis, so it is imperative to note the time of first stool
      passage. OBJECTIVE: The aim of this study was to assess the timing of first stool
      passage by preterm newborns in relation to antenatal exposure to magnesium
      sulfate (MgSO4) and a glucocorticoid (betamethasone) and to other perinatal
      factors, such as gestational age, respiratory distress syndrome (RDS), and time
      of first enteral feeding. METHODS: The subjects in this prospective, open study
      were preterm newbornswho were born before 37 weeks' gestation and admitted to the
      neonatal intensive care units of Baskent University, Adana Teaching and Research
      Center, and Inonu University, Turgut Ozal Medical Center, between June 2003 and
      August 2004. Effects of antenatal exposure to MgSO4 and glucocorticoid on the
      timing of first stool passage were assessed by comparing findings in exposed
      newborns to findings in an equal-sized group of gestational-age-matched subjects,
      derived from the study cohort, who were not exposed. Relationships between time
      of first stool passage and both gestational age and time of first enteral feeding
      were assessed. RESULTS: Two hundred premature newborns (112 males, 88 females)
      were included in the study. The median age at the time of first stool passage was
      16 hours, and 187 (93.5%) passed their first stool by 72 hours after birth.
      Delayed passage of first stool was noted in 33 (16.5%) newborns. One hundred
      sixty-eight (84.0%) newborns passed stool before enteral feeding was started.
      Gestational age and time to first enteral feeding were both significantly
      correlated with time of first stool passage (gestational age: r = -0.259, P <
      0.001; first enteral feeding: r = 0.168, P = 0.017). Time of first stool passage
      was significantly later in 46 newborns with RDS than in 46 gestation al-age
      matched newborns without RDS (mean [SD], 44.7 [39.7] vs 20.5 [18.4] hours,
      respectively; P < 0.05). The newborns whose mothers had received MgSO4 for
      tocolysis passed their first stool significantly later than gestational-age
      matched controls (mean [SD], 26.5 [26.9] vs 11.3 [12.1] hours, respectively; P <
      0.05). Antenatal exposure to betamethasone was not significantly correlated with
      timing of first stool passage. CONCLUSIONS: The results suggest that delayed
      passage of first stool in thesepreterm newborns was associated with gestational
      immaturity, delayed first enteral feeding, and RDS. Antenatal maternal exposure
      to MgSO4 was associated with later first stool passage in these preterm newborns,
      whereas antenatal exposure to betamethasone was not.

PMID- 24678099
TI  - Prospective, randomized, open-label, pilot clinical trial comparing the effects
      of dexamethasone coadministered with diclofenac potassium or acetaminophen and
      diclofenac potassium monotherapy after third-molar extraction in adults.
AB  - BACKGROUND: Patients who experience pain, swelling, and trismus after third-molar
      extraction are reported to experience a 3-fold higher rate of adverse effects
      (AEs) on quality of life compared with those who are asymptomatic after this
      surgery. Therefore, investigators emphasize the necessity for better control of
      this triad of sequelae. Steroids can reduce the risk for physiologic processes of
      inflammation, thereby suppressing the development of inflammation. OBJECTIVE: The
      aim of this study was to compare the effects of dexamethasone 8 mg IM and
      diclofenac potassium (K) 50 mg PO, dexamethasone 8 mg IM and acetaminophen 1000
      mg PO, and monotherapy with diclofenac K 50 mg PO on postoperative pain,
      swelling, and trismus after surgical removal of third molars. METHODS: This
      prospective, randomized, open-label pilot study was conducted at the Department
      of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos,
      Nigeria. Patients were randomly allocated to 1 of 3 treatment groups: concomitant
      treatment with dexamethasone 8 mg IM and diclofenac K 50 mg PO or acetaminophen
      1000 mg PO, or monotherapy with diclofenac K 50 mg PO. Overall analgesic efficacy
      of the drug combinations was assessed for 7 days postoperatively using a 4-point
      categorical pain-intensity rating scale (0 = no pain; 1 = mild pain; 2 = moderate
      pain; and 3 = severe pain). Facial swelling was measured in 1 dimension on days
      1, 2, and 7 after surgery using a tape measure placed from the tip of the tragus,
      to gonion, to the tip of the contralateral tragus, and trismus was assessed using
      interincisal mouth-opening ability, measured using a vernier-calibrated caliper
      on postoperative days 1, 2, and 7. Tolerability was assessed using direct
      questioning of the patients at follow-up visits. RESULTS: A total of 150 patients
      (50 per treatment group) were included in the analysis (76 women, 74 men; mean
      [SD] age, 26.8 [5.04] years [range, 18-45 years]; 100% Nigerian). The proportion
      of patients reporting no pain on the pain-intensity rating scale was
      significantly higher in the group receiving dexamethasone and diclofenac K
      compared with that in the groups receiving dexamethasone and acetaminophen or
      diclofenac K monotherapy (44% vs 22% and 24%, respectively; both, P < 0.05).
      Facial swelling was significantly less with dexamethasone and diclofenac K or
      dexamethasone and acetaminophen compared with diclofenac K alone (day 1: P =
      0.013 and P = 0.011, respectively; day 2: P = 0.002 and P = 0.004, respectively).
      However, trismus relief was statistically similar between the 3 treatment groups
      on postoperative days 1 and 2. No AEs or complications were recorded. CONCLUSION:
      In this open-label pilot study, concomitant treatment with dexamethasone and
      diclofenac K provided significant relief of postsurgical pain and swelling
      compared with dexamethasone and acetaminophen or monotherapy with diclofenac K
      after third-molar extraction in these patients.

PMID- 24678101
TI  - Steady-state pharmacokinetic properties of aripiprazole 10 mg PO g12h in Han
      Chinese adults with schizophrenia: A prospective, open-label, pilot study.
AB  - OBJECTIVES: The aims of this study were to investigate the pharmacokinetic (PK)
      properties of aripiprazole in the steady state in Han Chinese adults with
      schizophrenia and to compare them between Han Chinese and white populations
      described in the literature. METHODS: This prospective, open4abel, pilot study
      was conducted at the Mental Health Institute, Xiang-ya Second Hospital, Central
      South University, Changsha, China. Male and female hospitalized patients aged 18
      to 45 years diagnosed with Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV)-defined schizophrenia, with a Positive and Negative
      Syndrome Scale (PANSS) total score ?60 (indicating schizophrenia of at least mild
      severity) were eligible. On study days 1 and 2, patients were pretreated with
      aripiprazole 10 mg PO QD, followed by 10 mg g12h on days 3 to 21. Blood samples
      were drawn for analysis on day 21 before dosing and 1, 3, 4, 5, 12, 24, 48, 72,
      96, 144, and 192 hours after the morning dosing of aripiprazole on day 21.
      Patients received low-dose (25-100 mg/d) clozapine on day 25 until day 28. The
      samples were assessed using high-performance liquid chromatography-mass
      spectrometry and compartment model analysis for aripiprazole. PK properties
      included mean residence time (MRT) steady-state Cmax (Css max), time to Css max
      (Tmax), elimination t/12, apparent oral clearance (CL/F), and apparent volume of
      distribution (V/F). Adverse effects were monitored using physical examination
      (including vital sign measurements), electrocardiography, electroencephalography,
      and clinical laboratory testing (including biochemistry, hematology, and
      urinalysis) at baseline and at the end of the study. Patients were asked about
      adverse events on days 1 to 7 and at random intervals thereafter. Patients were
      also instructed to report any spontaneous symptoms they experienced. RESULTS:
      Twelve patients were enrolled (6 men, 6 women; mean [SD] age, 26.1 [7.0] years;
      mean [SD] weight, 56.6 [9.0] kg; mean [SD] PANSS score, 116.8 [12.2]).
      Aripiprazole exhibited linear kinetic characteristics on a 2-compartment model.
      After multiple oral doses (10 mg g12h), the mean (SD) t1/2, Css max, Tmax, MRT,
      V/F, and CL/F were 62.2 (9.0) hours, 557.3 (135.5) ng/mL, 2.6 (1.1) hours, 84.5
      (11.2) hours, 173 (48) L, and 1.9 (0.5) L/h, respectively. In Chinese patients,
      the t/12 values were numerically similar (62.2 [9.0] vs 68.1 [22.9] hours); Css
      max values were numerically higher (557.3 [135.5] vs 393 [181 ] ng/mL); and V/F
      and CL/F values were numerically lower (V/F: 173 [48] vs 196 [66] L; CL/F: 1.9
      [0.5] vs 3.4 [1.6] L/h) compared with healthy white male volunteers. Adverse
      effects were mild to moderate: lightheadedness (5 of 12 patients), somnolence
      (3), tachycardia (3), hypodynamia (2), and extrapyramidal symptoms (EPS) (1). The
      EPS (convulsive movement of the muscles related to the larynx) led to one
      patient's discontinuation of the study. CONCLUSIONS: In this small pilot study of
      the PK properties of aripiprazole 10 mg PO g12h in Han Chinese patients with
      schizophrenia, the mean t1/2 value was numerically similar to that previously
      reported in a population of healthy white male volunteers. However, the mean Css
      max value was numerically higher, and V/F and CL/F values were numerically lower,
      compared with those in healthy white male volunteers.

PMID- 24678100
TI  - Influences of age, sex, and LDL-C change on cardiovascular risk reduction with
      pravastatin treatment in elderly Japanese patients: A post hoc analysis of data
      from the Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE).
AB  - BACKGROUND: The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE)
      found that the prevalence of cardiovascular events (CVEs) was significantly lower
      with standard-dose (10-20 mg/d) pravastatin treatment compared with low-dose (5
      mg/d) pravastatin treatment in elderly (aged ? 60 years) Japanese patients with
      hypercholesterolemia. Small differences in on-treatment total cholesterol and low
      density lipoprotein cholesterol (LDL-C) levels between the 2 dose groups in the
      PATE study were associated with significant differences in CVE prevalence.
      However, the reasons for these differences have not been determined. How sex and
      age differences influence the effectiveness of pravastatin also remains unclear.
      OBJECTIVES: The aims of this study were to determine the relationship between
      reduction in LDL-C level and CVE risk reduction in the PATE study and to assess
      the effects of sex and age on the effectiveness of pravastatin treatment
      (assessed using CVE risk reduction). METHODS: In this post hoc analysis, Cox
      regression analysis was performed to study the relationship between on-treatment
      (pravastatin 5-20 mg/d) LDL-C level and CVE risk reduction using age, sex,
      smoking status, presence of diabetes mellitus and/or hypertension, history of
      cardiovascular disease (CVD), and high-density lipoprotein cholesterol level as
      adjustment factors. To explore risk reduction due to unspecified mechanisms other
      than LDLrC reduction, an estimated Kaplan-Meier curve from the Cox regression
      analysis was calculated and compared with the empirical (observed) Kaplan-Meier
      curve. RESULTS: A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8
      [5.7] years) were enrolled in PATE and were followed up for a mean of 3.9 years
      (range, 3-5 years). Of those patients, 50 men and 173 women were ?75 years of
      age. Data from 619 patients were included in the present analysis. In the
      calculation of model-based Kaplan-Meier curves, data from an additional 32
      patients were excluded from the LDL-C analysis because there were no data on
      pretreatment LDL levels; hence, the data from 587 patients were analyzed. A
      reduction in LDL-C level of 20 mg/dL was associated with an estimated CVE risk
      reduction of 24.7% (hazard ratio [HR] = 0.753; 95% CI, 0.625-0.907; P = 0.003).
      Risk was reduced by 22.2% in patients aged <75 years (HR = 0.778; 95% CI, 0.598
      1.013; P = NS) and 29.9% in patients aged ?75 years (HR = 0.701; 95% CI, 0.526
      0.934; P = 0.015). The risk reductions were 19.8% in women (HR = 0.802; 95% CI,
      0.645-0.996; P = 0.046) and 35.8% in men (HR = 0.642; 95% CI, 0.453-0.911; P =
      0.013). The risk reduction was 32.4% in patients without a history of CVD at
      enrollment (HR = 0.676; 95% CI, 0.525-0.870; P = 0.002) and 15.1% in those with a
      history of CVD (HR = 0.849; 95% CI, 0.630-1.143; P= NS). The estimated Kaplan
      Meier curve strongly suggested that the effects of pravastatin were only
      partially associated with changes in LDLrC level. CONCLUSIONS: The results from
      this post hoc analysis suggest that pravastatin 5 to 20 mg/d might elicit CVE
      risk reduction by mechanisms other than cholesterol-lowering effects alone. They
      also suggest that pravastatin treatment might be effective in reducing the risk
      for CVEs in both female and male patients aged ?75 years.

PMID- 24678102
TI  - Correlation of thiopurine methyltransferase activity and 6-thioguanine nucleotide
      concentration in Han Chinese patients treated with azathioprine 25 to 100 mg: A 1
      year, single-center, prospective study.
AB  - BACKGROUND: Of the enzymes involved in the metabolism of azathioprine, thiopurine
      methyltransferase (TPMT) is the one characterized by genetic polymorphisms and
      ethnic variations. There have been several studies of the ethnic variations in
      phenotype and genotype of TPMT, although few have assessed the possible
      correlation between TPMT activity and 6-thioguanine nucleotide (6-TGN)
      concentrations. OBJECTIVE: The aim of this study was to examine the relationship
      between TPMT activity and the steady-state concentration (Css) of 6-TGN, the
      primary active metabolite of azathioprine, in red blood cells (RBCs) in Han
      Chinese patients treated with azathioprine. METHODS: Han Chinese patients aged 18
      to 60 years with immunosuppression and normal hepatic and renal function who had
      been receiving a stable dose (25-100 mg/d) of oral azathioprine as a part of
      their regular anti-immunosuppression regimen for at least 10 days were recruited
      for this 1-year, single-center, prospective study. Azathioprine was administered
      PO QD in the morning, in combination with a stable regimen of other
      immunosuppressive drugs, for 1 year. At 1 year, blood samples were drawn just
      before the ingestion of azathioprine. TPMT activity and 6-TGN Css in RBCs were
      determined in our laboratory using high-performance liquid chromatography.
      Adverse drug events were monitored by a patient questionnaire and laboratory
      testing. Out of the initial cohort, several patients were concurrently enrolled
      in a subanalysis in which the effect of TPMT polymorphism on the pharmacokinetic
      properties of 6-mercaptopurine, the intermediate metabolite of azathioprine, was
      examined. RESULTS: Nineteen patients (14 women, 5 men; mean [SD] age, 41 [9.6]
      years [range, 22-59 years]; mean [SD] weight, 62 [12] kg) were included in the
      study; 7 were included in the subanalysis. A significant negative correlation was
      found between TPMT activity and 6-TGN Css in RBCs (r = -0.712; P = 0.001); when
      the outlier data were removed, no significant correlation was found. Mean (SD)
      TPMT activity was 12.95 (3.07) nmol/h . mL(-1) RBCs and the interindividual CV
      was 23.68%. Mean (SD) 6-TGN CSS was 42.95 (41.98) ng/8 * 108 RBCs and the
      interindividual CV was 97.74% (N = 19), while the intraindividual CV of 6-TGNs
      within 8 hours after azathioprine ingestion was between 4.23% and 7.37% (n = 7).
      No significant correlation was found between 6-TGN Css in RBCs and the dose of
      azathioprine used. One patient's treatment was discontinued because her white
      blood cell count decreased to < 4 * 109 cells/L, indicating myelotoxicity; the
      t/12 of 6-TGNs in this patient was 5.85 days. Treatment was well tolerated by all
      other patients. CONCLUSION: In this small study, a significant negative
      correlation was found between TPMT activity and 6-TGN concentration in the RBCs
      of these Han Chinese patients. However, the correlation was not significant when
      data from 1 patient with low TPMT activity were excluded.

PMID- 24678103
TI  - Duloxetine in the long-term management of diabetic peripheral neuropathic pain:
      An open-label, 52-week extension of a randomized controlled clinical trial.
AB  - BACKGROUND: Duloxetine hydrochloride, a selective serotonin (5-HT) and
      norepinephrine (NE) reuptake inhibitor, is relatively balanced in its affinity
      for both 5-HT and NE reuptake inhibition and is the first US Food and Drug
      Administration-approved prescription drug for the management of diabetic
      peripheral neuropathic pain (DPNP). OBJECTIVES: The aim of this study was to
      determine whether management of DPNP with duloxetine interferes with the
      treatment of diabetes. It also examined the tolerability of long-term exposure to
      duloxetine with regard to the progression of diabetic complications, and assessed
      the impact of DPNP management with duloxetine versus routine care. METHODS: This
      was a 52-week, multicenter, re-randomized, open-label extension of a parallel,
      double-blind, randomized, placebo-controlled, acute (12-week) study. Patients who
      completed the duloxetine or placebo acute treatment period were randomly
      reassigned in a 2:1 ratio to treatment with duloxetine 60 mg BID or routine care
      for an additional 52 weeks. The study included male and female outpatients aged
      >=18 years with a diagnosis of DPNP caused by type 1 or type 2 diabetes. Over the
      course of the 52-week study, visits were scheduled on the following weeks (of the
      extension phase of the study): 1 (via phone only), 2, 4, 8, 12, 20, 28, 40, and
      52. Tolerability was assessed by review and analyses of discontinuation rates,
      adverse events (AEs), laboratory data, vital signs, electrocardiographic results,
      concomitant medications, and diabetic complications. Treatment-emergent AEs
      (TEAEs) were defined as AEs that appeared during therapy (were not present at
      baseline) or were exacerbated during treatment. Data on AEs and concomitant
      medications were collected at every visit. Data on blood pressure, heart rate,
      and significant hypoglycemic events were collected at every visit starting from
      week 2. Fasting clinical chemistry and electrolyte group laboratory assessments
      were done at every visit, starting from week 4. Electrocardiographic data was
      collected at weeks 4 and 52, and glycosylated hemoglobin and lipid profile data
      were collected at weeks 20 and 52. Hematology and urinalysis laboratory
      assessments and diabetic complication assessments were done at week 52. All
      safety data was assessed in cases of early discontinuation. Treatment differences
      on quality of life (QOL) were compared using the Short Form-36 Health Status
      Survey (SF-36) and the EQ-5D instrument of the European Health-Related Quality of
      Life Measures. This was assessed at the last visit or at early discontinuation.
      RESULTS: The open-label extension-phase study included 337 patients (duloxetine,
      n = 222; routine care, n = 115). For the duloxetine group, mean age was 60.2
      years, 61.3% were male, and 78.4% were white. For the routine-care group, mean
      age was 58.9 years, 60.0% were male, and 74.8% were white. Mean weight was 95.3
      kg for both groups. None of the TEAEs occurred significantly more often in the
      duloxetine-treated group than in the routine-care-treated group. No TEAEs were
      reported by >10% of patients in the duloxetine group. The TEAEs reported by >10%
      of patients in the routine-care group included dizziness (11.3%), somnolence
      (13.0%), headache (10.4%), and vomiting (10.4%). No significant differences were
      found between treatment groups in the occurrence of serious AEs or in the number
      of patients discontinuing because of AEs. Duloxetine was significantly better
      than routine care on the bodily pain subscale of the SF-36 (mean change: 1.5 vs 
      4.1; P= 0.021) and on the EQ-5D (mean change: -0.00 vs -0.09; P = 0.001).
      CONCLUSIONS: Over 52 weeks of follow-up, treatment of these diabetic patients
      with duloxetine for peripheral neuropathic pain was associated with outcomes
      similar to, or significantly better than, that of routine care on most measures
      of tolerability, diabetic complications, and QOL.

PMID- 24678104
TI  - Quality of life in patients with functional dyspepsia: Short- and long-term
      effect of Helicobacter pylori eradication with pantoprazole, amoxicillin, and
      clarithromycin or cisapride therapy: A prospective, parallel-group study.
AB  - BACKGROUND: Quality of life (QOL) is impaired in functional dyspepsia (FD).
      Little is known about the effects of different therapies on the QOL profile in
      patients with this condition. OBJECTIVES: The aims of this study were to measure
      baseline QOL in patients with FD and to assess changes in QOL over time
      associated with Helicobacter pylori eradication and prokinetic treatment. The
      primary and secondary end points were the improvement in QOL 6 weeks and 1 year
      after successful eradication of the infection or prokinetic therapy. METHODS:
      This 1-year, single-center, prospective, open-label, controlled, parallel-group
      trial was conducted at the Department of Gastroenterology, Ferencvdros Health
      Centre, Budapest, Hungary. The Functional Digestive Disorder Quality of Life
      (FDDQoL) Questionnaire (MAPI Research Institute, Lyon, France) was translated and
      validated previously in Hungarian. Male and female subjects aged 20 to 60 years
      were enrolled and classified as H pylori positive (HP+), H pylori negative (HP-)
      with FD, or healthy (control group). The HP+ patients received pantoprazole 40 mg
      BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID for 7 days, followed by
      on-demand ranitidine (150-300 mg/d) for 1 year. The HP- patients received the
      prokinetic cisapride 10 mg TID for 1 month, followed by on-demand cisapride (10
      20 mg/d) for 1 year. The FDDQoL questionnaire was completed by all 3 groups on
      enrollment, at 6 weeks, and 1 year. RESULTS: A total of 101 HP+ patients, 98 HP-
      patients, and 123 healthy controls were included in the study (185 women, 137
      men; mean age, 39.0 ears). The mean (SD) baseline QOL scores were significantly
      lower in the HP+ group (53.3 [9.6]; 95% CI, 54.4-58.2) and the HP- groups (50.0
      [9.8]; 95% CI, 58.0-62.0) compared with that in healthy controls (76.2 [8.7]; 95%
      CI, 74.6-77.8) (both, P < 0.001). Analysis of the short-term domain scores found
      that the HP+ group had significantly decreased scores in 6 of 8 domains: daily
      activities (P = 0.005), anxiety level (P = 0.02), diet (P = 0.008), sleep (P <
      0.001), discomfort (P = 0.004), and disease control (P = 0.02); the HP- group had
      significantly decreased scores in 5 of 8 domains: daily activities (P < 0.001),
      diet (P = 0.004), sleep (P = 0.005), discomfort (P < 0.001), and disease control
      (P = 0.02). Eradication of the infection was successful in 77/101 (76.2%) of the
      patients on intent-to-treat analysis and 77/94 (81.9%) on per-protocol analysis.
      Eradication was associated with an increase in mean (SD) QOL score to 70.8 (10.7)
      at 6 weeks (95% CI, 63.3-73.2; P < 0.001 vs baseline) and to 75.3 (9.3) at 1 year
      (95% CI, 73.2-77.5; P= 0.05 vs 6 weeks). In the HP- group, the QOL score
      increased to 73.3 (9.7) (95% CI, 71.3-75.4; P < 0.001 vs baseline) at 6 weeks of
      cisapride treatment and to 76.5 (8.5) at 1 year (95% CI, 74.5-78.4; P = 0.06 vs 6
      weeks). Most of the impaired domain scores improved significantly after both
      treatments. The short-term effect size was 1.48 in HP+ and 1.35 in HP- patients.
      Adverse events (AEs) occurred in 22 (21.8%) patients in the HP+ group (nausea, 8
      [7.9%] patients; diarrhea, 5 [5.0%]; loss of appetite, 5 [5.0%]; stomatitis, 5
      [5.0%]; abdominal pain, 4 [4.0%]; bloating, 4 [4.0%]; headache, 4 [4.0%];
      vomiting, 4 [4.0%]; constipation, 3 [3.0%]; and vaginitis, 3 [3.0%]). In HP-
      cases, AEs occurred in 9 (9.2%) patients (abdominal cramps, 7 [7.1%]; diarrhea, 4
      [4.1%]; and nausea, 3 [3.1%]). CONCLUSION: In this study in patients with FD and
      healthy controls, eradication of H pylori infection in infected patients and
      cisapride treatment in uninfected patients reversed low QOL scores during the 1
      year follow-up period.

PMID- 24678105
TI  - Combination of fenofibrate plus low-dose nicotinic acid added to statin treatment
      in type 2 diabetes: An open-label, crossover study.
AB  - BACKGROUND: Plasma lipid abnormalities commonly persist in patients with diabetic
      dyslipidemia in spite of statin monotherapy. OBJECTIVE: The aim of this study was
      to determine whether fenofibrate plus low-dose nicotinic acid adequately improves
      the lipoprotein profile in patients with diabetic dyslipidemia who are being
      treated with a statin. METHODS: In this open-label, crossover study, patients
      with type 2 diabetes mellitus who were receiving statin treatment were enrolled
      at the Lipid Clinic of the Veterans Affairs Medical Center, Dallas, Texas, and
      administered simvastatin 20 mg/d for 8 weeks. At the end of the 8-week period,
      fenofibrate 160 mg/d was added for 8 weeks, followed by the addition of extended
      release nicotinic acid 1 g/d for an additional 8 weeks. The first subject was
      recruited on September 25, 2003, and the last subject was recruited on September
      28, 2004. Liver function tests, creatine phosphokinase activity, and blood
      glucose levels were assessed every 4 weeks to assess tolerability. Levels of
      fasting plasma lipids and lipoprotein cholesterol were measured every 8 weeks on
      3 consecutive days in each patient; C-reactive protein, lipoprotein pattern, and
      glycosylated hemoglobin levels were assessed once every 8 weeks. Plasma levels of
      total cholesterol, triglycerides, very-low-density lipoprotein plus intermediate
      density lipoprotein cholesterol (VLDL+IDL-C), low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B
      were also measured. RESULTS: Twenty-six patients were enrolled in the study and
      20 patients (18 men, 2 women; mean [SD] age, 58.8 [6.5] years) completed it. The
      mean plasma triglyceride level was significantly decreased (-29.2%; P= 0.004) and
      the mean HDL-C level was significantly increased (+13.5%; P < 0.001) with 3-drug
      treatment (simvastatin + fenofibrate + extended-release nicotinic acid) compared
      with simvastatin monotherapy. Significant reductions in plasma levels of VLDL+IDL
      C (-35.7%; P = 0.001), VLDL+IDL-apolipoprotein B (-30%; P = 0.005), non-HDL-C (
      12.9%; P = 0.001), and total-apolipoprotein B (-17.9%; P < 0.001) were seen with
      the 3-drug treatment compared with simvastatin alone. Compared with simvastatin
      monotherapy, simvastatin + fenofibrate-treated (2-drug treatment) patients had
      significantly lower plasma levels of triglycerides (-24.9%; P = 0.014) and
      significantly higher levels of HDL-C (+5.4%; P = 0.008). Significant reductions
      were also seen in levels of VLDL+IDL-C (-28.6%; P = 0.004), VLDL+IDL
      apolipoprotein B (-26.7%; P < 0.001), non-HDL-C (-9.1 %; P= 0.004), and total
      apolipoprotein B (-12.3%; P < 0.001) in the 2-drug treatment group compared with
      the simvastatin monotherapy group. The administration of 3-drug treatment was
      associated with improved responses in all lipoprotein fractions, although only
      the increase in HDL-C level was statistically significant (+7.7%; P = 0.008)
      compared with 2-drug treatment. CONCLUSIONS: Treatment with the 3-drug regimen
      was associated with a significant reduction in triglyceride levels compared with
      simvastatin monotherapy. However, there was not a significant incremental
      reduction in triglyceride levels when nicotinic acid was added to the 2-drug
      treatment, suggesting that the triglyceride-lowering effect of fenofibrate +
      nicotinic acid is not cumulative. To obtain clinically meaningful responses,
      particularly for the treatment of elevated HDL-C, higher doses of nicotinic acid
      might be required.

PMID- 24678106
TI  - Effects of a 250-mL enema containing sodium phosphate on electrolyte
      concentrations in healthy volunteers: An open-label, randomized, controlled, two
      period, crossover clinical trial.
AB  - BACKGROUND: Enemas are used by individuals with constipation and are often
      required before certain medical diagnostic procedures and surgical interventions.
      However, abnormalities in serum electrolyte concentrations have been associated
      with enema use. OBJECTIVE: The aim of this study was to determine the changes in
      serum electrolyte concentrations (phosphorus, calcium, sodium, and potassium) and
      urinary phosphorus elimination after the administration of a sodium phosphate
      enema. METHODS: Healthy volunteers aged 35 to 70 years were eligible for this
      open-label, randomized, controlled, 2-period, crossover clinical trial at the
      Clinical Research Unit of the University Hospital of Navarra, Pamplona, Spain.
      The study comprised 2 one-day periods separated by a 7-day washout. All subjects
      were randomly assigned in a 1:1 ratio to 1 of 2 study sequences: (1) a single
      dose of Enema Casen(r) 250 mL in the first period followed by no treatment
      (control) in the second period, or (2) no treatment in the first period followed
      by a single dose of the study drug in the second period. The sequence of
      treatment was assigned using a randomization table that was prepared before the
      beginning of the study. Serum concentrations of phosphorus, sodium, potassium,
      and calcium were measured in both periods. Urinary phosphorus elimination was
      measured for 12 hours after enema administration (Ae0-12) in a subset of the
      subjects in the second period. Adverse events (AEs) were monitored by the
      investigators throughout the study. Normal ranges for the electrolytes were as
      follows: phosphorus, 2.5 to 5 mg/dL; calcium, 8.5 to 10.5 mg/dL; sodium, 135 to
      145 mEq/L; and potassium, 3.5 to 5 mEq/L. RESULTS: Twenty-four subjects (12 men,
      12 women; mean [SD] age, 47.8 [9.6] years [range, 36-68 years]) participated in
      the study. All of the subjects were white and none were smokers. Twelve hours
      after enema administration, mean serum phosphorus and sodium concentrations
      increased by a mean of 1.18 mg/dL and 1.32 mEq/L, respectively (both, P < 0.001).
      Mean serum phosphorus concentrations were above the upper limit of normal (5
      mg/dL) at 30 and 60 minutes after enema administration. In all subjects the
      values returned to normal within 4 hours after enema administration; a meal was
      provided after a 3-hour fast. Four subjects (16.7%) had >=1 serum phosphorus
      concentration measurement >=7 mg/dL, a value that is considered serious
      hyperphosphatemia. A statistically significant correlation was found between
      phosphorus Cmax and enema retention time (r (2) = 0.452; P < 0.001). No abnormal
      serum concentrations were obtained for the other electrolytes measured.
      Phosphorus Ae0-12 was increased after enema administration by 86% (P < 0.001). No
      serious AEs were observed, although 13 AEs were reported in 9 subjects. None of
      the changes in serum electrolyte concentrations were associated with clinical
      symptoms. CONCLUSIONS: Administration of an enema containing 250 mL of sodium
      phosphate was associated with serum phosphorus concentrations of >=7 mg/dL in
      16.7% of the healthy subjects who participated in the study; however, none of
      those subjects experienced hypocalcemia. Enema retention time was significantly
      correlated with the degree of phosphatemia.

PMID- 24678107
TI  - Hormone profile in acute psychotic disorders: A cross-sectional comparison of
      serum hormone concentrations in treated and untreated male patients with
      schizophrenia.
AB  - BACKGROUND: Antipsychotic drugs for the treatment of schizophrenia provide
      effective treatment of psychotic symptoms but might lead to neuroendocrine
      abnormalities. OBJECTIVE: The aim of this study was to assess hypothalamic
      pituitary-gonadal (HPG) axis function by comparing serum hormone profiles of
      newly admitted patients with psychotic disorders who were receiving antipsychotic
      drugs with those who were antipsychotic-drug-free during the preceding 6 months.
      METHODS: Adult male patients admitted during a 1-year period (December 1999 to
      December 2000) to 1 of 2 Brazilian public psychiatric inpatient units that
      provide care for severely ill patients were eligible for this cross-sectional
      study if they had a diagnosis of schizophrenia based on the criteria given in the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and a
      score >24 on the Brief Psychiatric Rating Scale. On the morning after admission,
      serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), sex hormone-binding globulin (SHBG), prolactin, free testosterone (FT), and
      total testosterone (TT) were determined. A commercial laboratory provided the
      normal serum hormone concentrations of healthy Brazilian men in the same age
      range as that of the study patients. RESULTS: Sixty-three adult male patients,
      aged 18 to 55, were included in the study. Forty-eight (76.2%) patients (mean
      [SD] age, 30.6 [8.9] years) were receiving antipsychotic drugs (treated). Fifteen
      (23.8%) patients (mean [SD] age, 36.5 [9.8] years) were antipsychotic-drug-free
      for 6 months before admission (untreated). The only significant between-group
      difference was for disease duration (treated, 7.6 [8.1] years vs untreated, 12.3
      [9.7] years; P = 0.044). Treated patients were more likely to have higher
      dispersed serum hormone concentrations than the untreated patients. Serum
      concentration of FSH was numerically higher in the treated patients than in the
      untreated patients, although the difference was not statistically significant.
      Compared with the control group (1436 men and women for prolactin; 226 men for
      LH; 207 for FSH; 128 for TT; 128 for FT; and 128 for SHBG), patients in the
      treated group had significantly different mean [SD] serum concentrations of all
      hormones (treated vs control: prolactin, 24.3 [23.7] MUg/L vs 6.8 [0.12] MUg/L, P
      < 0.001; LH, 4.9 [3.4] U/L vs 3.3 [0.13] U/L, P = 0.001; FSH, 4.4 [3.9] U/L vs
      3.0 [0.06] U/L, P = 0.025; TT, 17.5 [7.8] nmol/L vs 20.1 [1.64] nmol/L, P =
      0.004; FT, 0.056 [0.08] nmol/L vs 0.06 [0.003] nmol/L, P < 0.001; and SHBG, 33.3
      [18.9] nmol/L vs 48.4 [1.45] nmol/L, P= 0.002). Compared with the control group,
      patients in the untreated group had significantly different mean (SD) serum
      concentrations of all hormones except FSH and TT (untreated vs control:
      prolactin, 19.9 [12.8] MUg/L vs 6.8 [0.12] MUg/L, P = 0.001; LH, 6.0 [1.9] U/L vs
      3.3 [0.13] U/L, P = 0.002; FT, 0.08 [0.04] nmol/L vs 0.06 [0.003] nmol/L, P=
      0.001; and SHBG, 26.6 [11.6] nmol/L vs 48.4 [1.45] nmol/L, P < 0.001). No
      differences were found between the TT distribution curve of the control group and
      that of the untreated patients. CONCLUSION: This study supports further
      investigation of a potential difference in the HPG axis among treated and
      untreated patients with schizophrenia and those who do not have that condition.

PMID- 24678109
TI  - Effects of trypan blue on corneal endothelium and anterior lens capsule in albino
      wistar rats: An investigator-masked, controlled, two-period, experimental study.
AB  - BACKGROUND: The development of continuous curvilinear capsulorrhexis (CCC) has
      contributed significantly to the tolerability and effectiveness of cataract
      extraction and intraocular lens implantation. Staining of the anterior capsule
      has become a popular method of increasing visibility when performing CCC.
      OBJECTIVE: The aim of this study was to determine, using scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM), the highest
      concentrations of trypan blue dye that would not cause long-term toxicity after
      injection into the anterior chamber of rat eyes. METHODS: The eyes of healthy
      female albino Wistar rats were used in this investigator-masked, controlled, 2
      period, experimental study conducted over 12 weeks at the Dicle University
      Experimental Animal Laboratory, Diyarbakir, Turkey. The rats were randomly
      divided into 5 groups of 4 using a random-number table. Each rat was administered
      a 0.05-mL injection of trypan blue into the right eye in 1 of the following
      concentrations: 0.4%, 0.2%, 0.1%, 0.05%, or 0.025%. A 0.05-mL pH-balanced saline
      solution was injected into the left eye of each rat to act as a control. At 1 day
      after injection and 4 weeks after injection (early period), 1 rat from each
      concentration group was euthanized and their eyes were enucleated. At 12 weeks
      after injection (late period) the remaining 2 rats from each group were
      euthanized and their eyes were enucleated. Corneal endothelial cells and the
      anterior lens capsule of the enucleated eyes were analyzed using SEM and TEM, and
      the results were compared with those of the control group. In the TEM analysis,
      the primary end point was the histopathologic changes in the cellular organelles
      when compared with those in the control group. In the SEM analysis, the primary
      end point was changes in cell shape, intracellular junctions, and density of the
      microvilli when compared with those in the control group. RESULTS: Forty eyes
      from 20 albino Wistar rats (mean [SD] age, 8.2 [1.6] weeks; mean [SD] weight,
      175.6 [16.5] g) were used in the study. Each group of rats received a different
      concentration of trypan blue in the right eye. In the early period, both the 0.4%
      and 0.2% concentrations were associated with the impairment of the hexagonal
      structure of corneal endothelial cells and intercellular junctions. Those
      concentrations were also associated with an increased occurrence of cellular
      vacuolation, cytoplasmic edema, extensive granulation of the endoplasmic
      reticulum, pyknotic nuclei, and mitochondrial degeneration. In the late period,
      these changes were observed as persisting in a decreasing manner. With the 0.1%
      and 0.05% concentrations, the density of microvilli decreased, nuclei appeared
      normal, granulation of the endoplasmic reticulum and Golgi apparatus was active,
      and minimal levels of mitochondrial degeneration were observed. CONCLUSIONS: In
      this small experimental study in rat eyes, trypan blue at concentrations >0.025%
      was associated with impaired morphology and structure of corneal endothelial
      cells after short-term exposure. This effect continued in a decreasing fashion
      after long-term exposure. No significant changes were noted in the control group
      or the group administered the 0.025% concentration.

PMID- 24678110
TI  - Nitric oxide synthase inhibitors appear to improve wound healing in endotoxemic
      rats: An investigator-blinded, controlled, experimental study.
AB  - BACKGROUND: Although inflammation is a normal part of wound healing, if the
      inflammatory response is excessive the repair process might be prolonged. Nitric
      oxide (NO) has been implicated in healing inflammation and wounds. OBJECTIVE:
      Endotoxins and cytokines associated with sepsis induce NO synthesis in the
      tissues. This study used tensile strength and tissue hydroxyproline levels as
      proxies for wound healing to determine whether wound healing in the presence of
      endotoxemia is improved when NO synthase is inhibited by N-nitro-l-arginine
      methyl ester (L-NAME) or N (5)-(1-Imino-methyl)-l-ornithine (L-NIO). METHODS: In
      this investigator-blinded, controlled, experimental study, male Wistar albino
      rats (275-300 g) were divided into 4 groups. The first group received an
      intraperitoneal (IP) injection of Escherichia coli endotoxin 10 mg/kg and an SC
      injection of 0.9% sodium cloride (NaCl). The second group received IP E coli 10
      mg/kg and SC L-NAME 2 mg/kg. The third group received IP E coli 10 mg/kg and L
      NIO 10 mg/kg. The control group was administered an IP and an SC injection of
      0.9% NaCl. Each group received both injections at 24 and 16 hours before surgery.
      All rats underwent a 3-cm dorsal midline incision, which was subsequently closed.
      Five days after surgery, all rats were euthanized and skin from the healing wound
      was excised. Hydroxyproline levels and tensile strength were then measured.
      RESULTS: Forty-four male rats (mean age, 16 weeks; mean [SD] weight, 284 [16] g)
      were included in the study. Each of the groups receiving endotoxin (endotoxin, L
      NAME, and L-NIO groups) had 12 rats; the control group consisted of 8 rats. All
      the groups that received endotoxin showed significant declines in hydroxyproline
      levels versus controls (P < 0.001, P = 0.001, and P = 0.002, respectively).
      Compared with the control group, the endotoxin-only group had a significant
      reduction in both mean (SD) hydroxyproline levels and mean (SD) wound tensile
      strength (298.27 [17.66] vs 175.82 [18.73] g/cm2 and 7.16 [0.51] vs 4.01 [0.29]
      MUg/mg wet tissue; both, P < 0.001). Compared with the endotoxin- only group,
      rats that received L-NIO had significantly greater mean (SD) hydroxyproline
      levels and mean (SD) wound tensile strength (6.44 [0.34] vs 4.01 [0.29] MUg/mg
      wet tissue and 280.12 [14.38] vs 175.82 [18.73] g/cm(2); both, P < 0.001). Wound
      tensile strength in the L-NIO group was not significantly different from that in
      the control group. A significant difference was observed between the L-NIO and L
      NAME groups in wound tensile strength (280.12 [14.38] vs 241.38 [20.69] g/cm(2);
      P = 0.001), but not in tissue hydroxyproline levels. CONCLUSION: Inhibition of NO
      synthesis might improve wound tensile strength, which suggests a possible role
      for NO inhibitors in improved wound healing in the presence of endotoxemia.

PMID- 24678111
TI  - Effect of sevoflurane anesthesia on the severity of renal histopathologic changes
      in rabbits pretreated with gentamicin: A controlled, investigator-blinded,
      experimental study.
AB  - BACKGROUND: Inorganic fluoride and compound A are potential nephrotoxic products
      of sevoflurane, a halogenated inhalational general-anesthetic drug. OBJECTIVE:
      The aim of this study was to microscopically examine the effect of sevoflurane on
      the severity of renal histopathologic changes in rabbits pretreated with
      gentamicin. METHODS: In this controlled, investigator-blinded, experimental study
      at the Firat University School of Medicine, Elazig, Turkey, male New Zealand
      white rabbits (age range, 6-8 months; weight range, 2600-3400 g) were randomly
      divided into 4 groups of equal size. The gentamicin group received IM gentamicin
      10 mg/kg . d(-1) for 10 days. Rabbits in the sevoflurane group received pH
      balanced saline solution at a volume of 10 mg/kg . d(-1) for 10 days, equivalent
      to the volume of gentamicin administered to the gentamicin group. On day 11,
      anesthesia was induced with 8% sevoflurane in 50% oxygen and air using a suitable
      facemask. When a sufficient depth of anesthesia (loss of eyelash reflex and
      tolerance to tail-clamp stimuli) was reached (without a muscle relaxant), the
      rabbits were intubated (3-mm ID) and allowed to breathe spontaneously. End-tidal
      or end expiratory concentration of sevoflurane was then decreased to 4% and the
      rabbits were anesthetized at a flow rate of 4 L/min for 4 hours. The rabbits in
      the gentamicin + sevoflurane group were treated with IM gentamicin at a dosage of
      10 mg/kg . d(-1) for 10 days. On day 11, they were exposed to sevoflurane, as
      described for the sevoflurane group. The control group received IM pH-balanced
      saline solution for the duration of the study. Twenty-four hours after treatment
      completion, all rabbits were euthanized and kidney tissue samples were obtained.
      Histopathologic examinations were then carried out using light microscopy.
      Changes in renal histopathology were based on the percentage of acute tubular
      necrosis (ATN) and judged on a scale from none to severe. RESULTS: Forty male New
      Zealand white rabbits (mean [SD] age, 7 [0.49] months; mean [SD] weight, 2900
      [150] g) were divided into 4 groups of 10 rabbits each. Proximal renal tubule
      cell injury in the form of ATN (the mean score) was significantly greater in the
      3 treatment groups than in the control group (all, P < 0.001), especially at the
      corticomedullary junction. In the 3 treatment groups, the most severe renal
      damage observed was rated as mild (10%-25%). More rabbits in the gentamicin +
      sevoflurane group had mild renal damage (7) than in the gentamicin group (4) or
      the sevoflurane group (4), but the between-group differences were not
      statistically significant. CONCLUSION: In this experimental study of the effects
      of sevoflurane on the severity of renal histopathologic changes, a higher
      percentage of rabbits were observed to have greater renal damage in the
      gentamicin + sevoflurane group than the other groups. However, between-group
      differences did not reach statistical significance.

PMID- 24678112
TI  - In vitro effect of D-004, a lipid extract of the fruit of the cuban royal palm
      (Roystonea regia), on prostate steroid 5alpha-reductase activity.
AB  - BACKGROUND: D-004, a lipid extract of the fruit of the Cuban royal palm
      (Roystonea regia), has been found to reduce prostatic hyperplasia (PH) induced
      with testosterone (T), but not PH induced with dihydrotestosterone (DHT), in
      rodents, suggesting the inhibition of prostate 5alpha-reductase activity.
      OBJECTIVES: The aims of this study were to assess whether D-004 inhibits prostate
      5alpha-reductase activity in vitro and to examine the effects of D-004 on enzyme
      kinetics. METHODS: This experimental study was conducted at the Pharmacology
      Department, Center of Natural Products, National Center for Scientific Research,
      Havana, Cuba. Soluble rat prostate preparations were used as the source of 5alpha
      reductase, and ((3)H)-DHT production was measured to determine prostate 5alpha
      reductase activity. Cell-free rat prostate homogenates were pre-incubated with
      carboxymethyl cellulose 2% alone (control tubes) or D-004 (0.24-125 MUg/mL)
      suspended in the vehicle (treated tubes) for 10 minutes prior to adding the
      labeled substrate ((3)H)-T Once the reaction was stopped, sterols were extracted
      with chloroform and aliquots were applied on silica gel plates developed in
      benzene-acetone (4:1, v/v). Areas containing DHT were scraped and radioactivity
      was counted. The median inhibitory concentration (IC50) was determined by
      measuring the conversion of T to DHT The apparent Michaelis-Menten constant (Km)
      and Vmax values before and after adding D-004 were determined in kinetic studies
      using labeled T (0.5-25 MUmol/L). RESULTS: Compared with controls, D-004
      significantly and dose-dependently inhibited the enzymatic reaction at doses of
      1.95 to 125.0 MUg/mL) (all, P < 0.05). The IC50 of D-004 required to inhibit 5a
      reductase activity was 2.25 MUg/mL. Enzyme inhibition was noncompetitive, since D
      004 lowered the Vmax from 15.3 to 10.0 nmol DHT/min . mg(-1) protein, while the
      Km (4.54 MUmol/L) was almost unaffected. CONCLUSIONS: D-004 dose-dependently and
      noncompetitively inhibited in vitro 5alpha-reductase activity in soluble
      fractions of rat prostate. Although the extent of the maximal inhibition was high
      and the value of IC50 was low, the relevance of such inhibition requires further
      study in vivo.

PMID- 24678113
TI  - Plasma levels, tissue distribution, and excretion of radioactivity after single
      dose administration of ((3)H)-oleic acid added to D-004, a lipid extract of the
      fruit of Roystonea regia, in rats.
AB  - BACKGROUND: D-004, a lipid extract of the fruit of Roystonea regia, contains a
      mixture of fatty acids-mainly oleic, lauric, palmitic, and myristic acids, with
      oleic acid being among the most abundant-that has been found to reduce the risk
      for prostatic hyperplasia (PH) induced with testosterone (T) in rats. The
      pharmacokinetic profile of D-004 has not been reported. OBJECTIVE: The objective
      of this study in rats was to assess plasma levels, tissue distribution, and
      excretion of total radioactivity (TR) after single-dose administration of oral D
      004 radiolabeled with ((3)H)-oleic acid, as a surrogate for the pharmacokinetics
      of D-004. METHODS: This experimental study was conducted at the Pharmacology
      Department, Center of Natural Products, National Center for Scientific Research,
      Havana, Cuba. Single doses of suspensions of ((3)H)-oleic acid 0.16 MUCi/mg mixed
      with D-004 400 mg/kg (radioactive dose/animal 7.2 MUCi) were given orally to male
      Wistar rats weighing 150 to 200 g assigned to the treated or control group. Three
      rats were euthanized at each of the following times: 0.25, 0.5, 1, 1.5, 2, 4, 8,
      24, 48, 72, 96, and 144 hours after study drug administration. After
      administration, the rats euthanized at the last experimental time point were
      housed individually in metabolism cages. Urine and feces samples were collected
      daily. At each time point, blood samples were drawn and plasma samples were
      obtained using centrifugation. After euthanization, tissue samples (liver, lungs,
      spleen, brain, kidneys, adipose tissue, muscle, stomach, small and large
      intestines, adrenal glands, heart, testes, prostate, and seminal vesicles) were
      quickly removed, washed, blotted, and homogenized. Plasma (100 MUL), tissue
      aliquots (100 mg), feces (10 mg), and urine (100MUL) were dissolved and TR was
      measured. Samples were assayed in duplicate. Results were expressed in MUgEq of
      radio-labeled oleic acid per milliliter of plasma or urine or gram of tissue or
      feces. Plasma, tissue, feces, and urine samples of rats that did not receive
      ((3)H)-oleic acid were used as controls. Excretion was expressed as the
      percentage of the radioactivity excreted via each route with respect to the total
      radioactive dose administered to each rat. RESULTS: A total of 50 rats were
      included in the experiment (mean age, 4 weeks; mean weight, 310 g). Absorption
      was rapid; mean Cmax was 195.56 (31.12) MUgEq/mL, and mean Tmax was 2 hours.
      Thereafter, a biphasic decay of TR was found: a rapid first phase (t1/2alpha,
      1.33 hours), followed by a slower second elimination phase (t1/2beta, 36.07
      hours). Radioactivity was rapidly and broadly distributed throughout the tissues,
      with more accumulating in the prostate than elsewhere. In the first 8 hours,
      accumulation of TR was greatest in the prostate, followed by the liver, small
      intestine, and plasma. Subsequently, TR increased in the small intestine, while
      it decreased in the liver and plasma. In contrast, over the periods of 24 and 144
      hours after administration, TR increased in the adipose tissue, while it
      decreased in the other tissues and plasma. During those intervals, TR was
      greatest in the prostate, followed by adipose tissue. Mean peak radioactivity in
      the prostate (562.41 MUgEq/g) was reached at 4 hours and decreased slowly
      thereafter. The prostate had the highest values of t1/2beta and cumulative AUC
      compared with the other tissues and plasma. Mean (SD) TR was similar in feces
      (33.48% [4.90%]) and urine (28.96% [5.32%]), with total excretion being 62.40%
      (5.90%) of the administered dose. CONCLUSIONS: In this experimental study, after
      single-dose administration of oral D-004 radiolabeled with ((3)H)-oleic acid in
      rats, TR was rapidly and widely distributed across the tissues, with the prostate
      having the highest accumulation of radioactivity. Excretion of TR was limited,
      with similar amounts being excreted in feces and urine. The broad distribution of
      radiolabeled oleic acid and/or its metabolites suggests (SD) pharmacokinetic
      rationale for the effectiveness of D-004 in reducing the risk for PH induced with
      T in rats.

PMID- 24678115
TI  - Tolerability of intravenous pamidronate for the treatment of osteoporosis and
      other metabolic osteopathies: A retrospective analysis.
AB  - BACKGROUND: Intravenous disodium pamidronate has been described in the treatment
      of several osteopathies. Although tolerability has been found to be good in
      clinical trials, some mild to serious adverse events (AEs) have been reported.
      OBJECTIVES: The aims of this study were to analyze the toelrability of IV
      pamidronate in patients being treated for osteoporosis and other metabolic
      osteopathies and to describe particular patients with relative contraindications,
      because such cases are not commonly seen in daily clinical practice. METHODS: We
      performed a retrospective analysis of patients with different osteopathies who
      were administered IV infusions of pamidronate at doses ranging from 15 to 90
      mg/infusion and 15 to 900 mg/year. The study was conducted in patients who had
      received treatment at the Institute of Metabolic Investigations, University of
      Salvador, Buenos Aires, Argentina, between January 1995 and December 2003. To
      rule out dose-related AEs, a comparison was made between patients who received
      fewer IV infusions and had cumulative doses of 120 to 180 mg/y (less frequent
      administration [LFA] group) and those patients who received regular infusions and
      had cumulative doses of >180 mg/year (frequent administration [FA] group). To
      confirm data obtained from medical records and to assess the occurrence of AEs,
      attempts were made to interview all patients by phone. The following information
      was verified for each patient included in the study: the reason for treatment,
      documented evidence of current diagnostic criteria, and whether the dose
      administered was adequate to treat the patient's condition. RESULTS: Six hundred
      eight patients (464 [76.3%]women, 144 [23.7%]men; mean [SD] age, 69 [10] years)
      with various osteopathies (osteoporosis, 367 [60.4%] of the patients; Paget's
      disease, 172 [28.3%]; Sudeck's disease, 63 [10.4%]; multiple myeloma, 3 [0.5%];
      and bone metastases, 3 [0.5%]) were administered a total of 2933 IV infusions of
      pamidronate during the study period. We were able to confirm the clinical records
      of 69.4% (422/608) of the patients by telephone survey; 29.9% (124/415) of those
      patients experienced extraskeletal AEs (most commonly fever and flu-like symptoms
      [eg, headache, malaise, fatigue, chills, and asthenia]). The percentage of
      patients reporting AEs was significantly higher for the LFA group than that of
      the FA group (91.2 vs 19.5; P < 0.001), although factors other than the frequency
      of treatment might have had a bearing on this finding. All AEs were mild and
      transient in both groups of patients, and there were no reports of jaw
      osteonecrosis in either group. It should be noted that although LFA patients
      received lower doses of pamidronate per infusion than the FA group, they had
      higher cumulative doses/year. Biochemical variables for the entire study
      population were compared with baseline measurements, and no significant changes
      in mean values were observed. Both serum calcium and 25-hydroxy vitamin D levels
      remained within normal ranges. On the other hand, there was a transient decrease
      in white blood cell count (WBCC) in 73 (12.0%) patients, and leukopenia was
      observed in 8 (1.3%) patients. However, 5 of the 6 patients who were leukopenic
      at the beginning of treatment had normal WBCCs during follow-up. Platelet count
      decreased significantly in 20 (3.3%) patients, and 5 (0.8%) patients developed
      thrombocytopenia. Serum creatinine (sCreat) levels increased significantly in 91
      (15.0%) patients. This increase was transient and within normal limits (0.6-1.2
      mg/dL) in 79 (86.8%) of those patients but persistent in the other 12 (13.2%),
      all of whom received higher doses of pamidronate or had other risk factors for
      renal failure such as advanced age, diabetes, multiple myeloma, or an obstructor
      disease. Baseline sCreat level for 7 of these 12 patients was >1.20 mg/dL.
      CONCLUSIONS: Pamidronate administered IV was well tolerated when used for
      treating osteoporosis or other metabolic osteopathies in our study population.
      The clinical AEs observed with IV pamidronate administration were not serious and
      hematologic changes were mild, transient, and not associated with dose, time of
      treatment, or any particular underlying disease. An increase in sCreat level was
      the most frequent biochemical complication and was found in patients with
      additional risk factors for renal failure and particular diseases. Whether
      certain patients with risk factors for osteoporosis may require even fewer IV
      administrations of the drug is an issue that remains to be elucidated.

PMID- 24678116
TI  - Linezolid compared with vancomycin for the prevention of methicillin-resistant
      Staphylococcus aureus or Staphylococcus epidermidis vascular graft infection in
      rats: A randomized, controlled, experimental study.
AB  - BACKGROUND: Graft infections are severe complications of vascular surgery that
      may result in amputation or mortality. Staphylococci are the most frequent cause
      of vascular graft infections. OBJECTIVE: In this study we assessed the
      prophylactic efficacy of linezolid in comparison with vancomycin in preventing
      prosthetic vascular graft infection due to methicillin-resistant Staphylococcus
      aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE).
      METHODS: This randomized, controlled, experimental study using healthy adult
      (aged >5 months) male Wistar rats was conducted in the research laboratory of the
      Pamukkale University, Denizli, Turkey. The study consisted of an uncontaminated
      control group and 3 groups for both staphylococcal strains: a contaminated group
      that did not receive any antibiotic prophylaxis; a contaminated group that
      received preoperative intraperitoneal (IP) prophylaxis with vancomycin; and a
      contaminated group that received preoperative IP prophylaxis with linezolid. All
      rats received a vascular Dacron graft placed inside a subcutaneous pocket created
      on the right side of the median line. Sterile saline solution (1 mL), to which
      MRSA or MRSE at a concentration of 2 * 10(7) colony-forming units per milliliter
      had been added, was inoculated onto the graft surface using a tuberculin syringe
      to fill the pocket. The grafts were explanted 7 days after implantation and
      assessed by quantitative culture. RESULTS: Seventy rats (mean [SD]weight, 323.7
      [17.9]g; mean [SD]age, 5.98 [0.64] months) were evenly divided between the 7
      groups. Statistical analysis of the quantitative graft culture suggested that
      both vancomycin and linezolid were effective in significantly inhibiting
      bacterial growth when compared with the untreated contaminated groups (all, P <
      0.001). However, a statistically significant difference was not observed between
      the bacteria count in the vancomycin and linezolid prophylaxis groups. When a
      comparison was made between the bacterial growth in the contaminated control
      groups, MRSA had significantly greater affinity to the Dacron prostheses than
      MRSE (all, P < 0.001). CONCLUSION: Our study found that linezolid was as
      effective as vancomycin in suppressing colony counts in MRSA- or MRSE-infected
      vascular Dacron grafts in rats.

PMID- 24678117
TI  - The effects of exogenous l-carnitine on lipid peroxidation and tissue damage in
      an experimental warm hepatic ischemia-reperfusion injury model.
AB  - BACKGROUND: l-Carnitine is the essential endogenous factor for the transport of
      long-chain fatty acids from the cytoplasm to within the mitochondrion where the
      beta-oxidation process takes place. l-Carnitine is a superoxide scavenger and an
      antioxidant that possesses an anti-ischemic action and a stabilizing effect on
      cell membranes. It may be of help in liver ischemia reperfusion injury. RESULTS
      regarding the effects of l-carnitine on liver ischemia and reperfusion injury are
      few and conflicting. OBJECTIVE: The aim of this study was to investigate the
      efficacy of exogenous l-carnitine on lipid peroxidation and protecting liver at
      different stages of experimental total warm hepatic ischemia-reperfusion (TWHIR)
      procedure in rats. METHODS: This experimental study in healthy, weanling, male
      Wistar rats (weighing 180-200 g) was conducted at the Experimental Animal
      Research Laboratory of the Faculty of Medicine of Mersin University, Mersin,
      Turkey. Rats were randomly divided into 5 groups: (A) Control group; (B) TWHIR
      procedure only; (C) l-carnitine administered 2 hours before the TWHIR procedure;
      (D) l-carnitine administered just before the TWHIR procedure; and (E) l-carnitine
      administered after total warm hepatic ischemia but just before the reperfusion
      procedure. Total warm hepatic ischemia (via the Pringle maneuver) and reperfusion
      were performed for 45 and 30 minutes, respectively. l-Carnitine (200 mg/kg) was
      administered intravenously. At the end of each procedure a blood sample was drawn
      and total hepatectomy was performed following reperfusion. Malondialdehyde (MDA)
      and myeloperoxidase (MPO) levels of both plasma and liver tissue, total
      antioxidant capacity (TAOC), alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) levels in plasma, and histopathologic examination were
      analyzed to assess lipid peroxidation and damage in liver tissue. RESULTS: Thirty
      four rats (mean [SD]age, 59.26 [1.2]days; mean [SD] weight, 194.1 [5.1] g) were
      used in the study. There was a significant difference observed between groups A
      (n = 5) and B (n = 5) for all evaluation parameters. The TWHIR procedure
      performed in group B was associated with significant increases versus baseline in
      ALT, AST, MDA, and MPO in plasma, and MDA and MPO in liver tissue, but a
      significant decrease of TAOC in plasma. ALT, AST, serum and liver MDA, and MPO
      levels of group B were significantly higher than all groups administered l
      carnitine. l-Carnitine administration between total warm hepatic ischemia and
      reperfusion was associated with a significant attenuation in all parameters. The
      liver MDA levels of groups C (n = 8) and D (n = 8) were significantly lower than
      that of group E (n = 8) (mean [SD]: C, 16.53 [3.32] and D, 18.28 [1.67] vs E,
      23.05 [3.52]; P = 0.001 and P = 0.016, respectively). The mean (SD) liver MPO
      level of group C (1.09 [0.16]) was significantly lower than that of groups D
      (2.12 [0.25]) and E (2.11 [0.28]) (both, P = 0.001). The TAOC of group B (0.77
      [0.12]) was significantly lower than that of groups C (1.34 [0.19]) and D (1.08
      [0.20]) (P = 0.001 and P = 0.015, respectively). The TAOC of group C was
      significantly higher than that of the other l-carnitine groups (E, 0.94 [0.13])
      (P = 0.023 vs group D; and P = 0.001 vs group E). Histopathologic scores of
      groups A, C, and E were significantly lower than that of group B, but the
      difference between groups B and D was not statistically significant. CONCLUSIONS:
      In this experimental study, administration of exogenous l-carnitine was
      associated with significantly decreased lipid peroxidation in plasma and liver
      tissue when administered prior to a TWHIR procedure. In addition, l-carnitine
      seemed to be more effective with regard to decreasing lipid peroxidation in liver
      tissue when administered before warm hepatic ischemia. l-Carnitine was associated
      with significantly decreased leukocyte sequestration in plasma and liver tissue.
      A significant increase in TAOC was associated with l-carnitine administered prior
      to ischemia. These observations suggest that l-carnitine might have a protective
      effect against ischemia-reperfusion injury in rat liver tissue.

PMID- 24678120
TI  - The charles R. Ream, MD, award for excellence-2006.

PMID- 24678118
TI  - A review of the current place of glycopeptides in turkish medical practice.
AB  - BACKGROUND: Glycopeptide antibiotics are considered by many investigators to be
      the last resort in the treatment of gram-positive bacterial infections.
      OBJECTIVE: The aim of this review was to assess the place of glycopeptides in the
      treatment of common gram-positive bacteria in accordance with the current
      epidemiologic data in Turkey. METHODS: A search of both the English- and Turkish
      language literature indexed on MEDLINE, Ulakbim (Turkey), and Pleksus (Turkey)
      was performed using the terms: vancomycin, teicoplanin, and glycopeptides, or
      their Turkish-language counterparts. The complete texts of the articles found in
      these databases were obtained from the electronic library of Gulhane Medical
      Academy, Ankara, Turkey. Articles from regional journals, without the support of
      an electronic format, were obtained by direct communication. Articles of interest
      were those based on studies occurring in Turkish populations, with special
      consideration given to publications in press after 2002. RESULTS: Staphylococci
      were the most frequent gram-positive pathogens encountered in Turkish hospitals.
      Studies have found that ~74% of strains were Staphylococcus aureus and the
      remaining strains were coagulase-negative staphylococci (CoNS). Overall
      methicillin resistance in staphylococci was reported as ~60%. In Turkey, S aureus
      was one of the most common infectious agents found inside hospitals and is deemed
      a growing threat in the community. While the rate of methicillin resistance in
      community-acquired isolates is ~4%, the data from hospitals suggest that reduced
      resistance comprises most of the isolates. In the studies reviewed, older
      quinolones like ciprofloxacin and ofloxacin seem to be ineffective in nearly half
      of the S aureus isolates. Alternatives like rifampicin, gentamicin, tetracycline,
      trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, and erythromycin have had
      substantial resistance profiles in >50% of the strains. In recent Turkish
      studies, in vitro profiles of linezolid, quinupristin/dalfopristin (QD), and
      daptomycin have had positive results. As in the S aureus isolates, resistance
      trends have been observed in the CoNS group of pathogens. The possible use of
      beta-lactams seems restricted, and alternative approaches have become necessary.
      Quinolones, gentamicin, tetracycline, TMP/SMX, clindamycin, and erythromycin have
      resistance profiles of >50%. Although glycopeptide resistance was not detected,
      the frequency of heterogenous vancomycin-intermediate S aureus, a precursor to
      future resistance, was 13% in 1 study. Current studies in Turkey have found that
      Enterococcus faecalis comprises three quarters of enterococci while the rest are
      comprised of Enterococcus faecium. Initial studies performed with linezolid, QD,
      and daptomycin suggest that these drugs might be effective alternatives for
      future enterococcal infections that may have high glycopeptide resistance.
      Approximately 8% of the Streptococcus pneumoniae strains had high-level
      resistance in Turkey. However, 10 million units of crystallized penicillin or 3 g
      of oral amoxicillin maintains the optimum treatment of pneumococcal infections
      outside the central nervous system (CNS). Resistance profiles in third-generation
      cephalosporins in Turkey range between 2% and 2.5%. CONCLUSIONS: In Turkey, a
      review of the existing literature found that the current use of glycopeptides in
      pneumococcal infections is restricted to CNS infections facing therapeutic
      failure in due course. However, the belief that these drugs are the last resort,
      either in staphylococcal or enterococcal infections, is no longer valid. If a
      patient has a critical status due to probable gram-positive microorganisms,
      clinicians should consider the empiric use of glycopeptides. However, new
      molecules such as linezolid, QD, and daptomycin, offered for use in the treatment
      of gram-positive bacterial diseases, should be reserved for the future, when
      glycopeptides eventually become obsolete.

PMID- 24678121
TI  - Comparison of dexmedetomidine and midazolam for monitored anesthesia care
      combined with tramadol via patient-controlled analgesia in endoscopic nasal
      surgery: A prospective, randomized, double-blind, clinical study.
AB  - Abstract. BACKGROUND: Monitored anesthesia care (MAC) may be applied for
      septoplasty or endoscopic sinus surgery in which an adequate sedation and
      analgesia without respiratory depression are desired for comfort of both the
      patient and the surgeon. Several combinations with different agents have been
      used for this purpose in these patients. However, analgesic properties for these
      agents have not been reported. OBJECTIVE: The aim of this study was to
      investigate the analgesic and sedative effects of dexmedetomidine or midazolam
      infusion combined with tramadol that was used via patient-controlled analgesia
      (PCA), and to document the effects of these drugs on early cognitive functions.
      METHODS: This prospective, randomized, double-blind, clinical study enrolled
      patients undergoing septoplasty or endoscopic sinus surgery at the Abant Izzet
      Baysal University Hospital, Bolu, Turkey, between February and September 2006.
      Patients were randomly allocated in a 1:1 ratio into 1 of 2 groups: the
      dexmedetomidine group (group D) patients received IV dexmedetomidine 1 MUg/kg for
      10 minutes followed by continuous infusion of 0.5 MUg/kg . h(-1); and the
      midazolam group (group M) patients were administered a loading dose of IV
      midazolam 40 MUg/kg for 10 minutes followed by infusion at the rate of 50 MUg/kg
      . h(-1). A 1-minute bolus dose of IV tramadol (1.5 mg/kg) was administered in
      both groups 10 minutes after the administration of the primary drug, and
      continued via infusion using a PCA device. After baseline measurements, systolic
      arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial
      pressure (MAP), heart rate (HR), oxygen saturation, and rate of respiration were
      recorded after the loading dose of study drug, after the bolus tramadol dose, at
      10-minute intervals during the operation, and twice in the recovery rooms; 5
      minutes after arrival and 5 minutes before discharge. Verbal rating score (VRS)
      and Ramsay sedation score were determined at baseline (after surgery was
      started), every 10 minutes thereafter until the end of the operation, and 2 times
      during recovery. All patients were assessed with the Wechsler Memory Scale
      Revised at baseline (preoperatively) and 4 hours after the operation. RESULTS:
      Seventy patients were enrolled in the study and randomly assigned to 1 of 2
      groups: group D (sex, male/female, 23/12; mean [SEM] age, 32.53 [2.07] years;
      mean [SEM] weight, 73.03 [2.41] kg) or group M (sex, male/female, 21/14; mean
      [SEM] age, 34.43 [1.83] years; mean [SEM] weight, 67.90 [2.32] kg). All
      hemodynamic parameters (SAP, DAP, MAP, HR) were significantly higher in group M
      compared with group D from the onset of the surgery to discharge time (P < 0.05).
      Pain and sedation scores were similar in both groups, but the amount of PCA
      administered rescue tramadol was significantly higher in group M (P = 0.001). A
      higher, though not statistically significant, prevalence of adverse events (ie,
      hypotension, bradycardia, and perioperative nausea and vomiting) were observed in
      group D. Postoperative logical verbal memory and digit span values were
      significantly higher in group D when compared with group M (P < 0.05).
      Postoperative digit span and visual reproduction scores were significantly higher
      than preoperative values in group D (P < 0.05). Postoperative personality
      functioning scores were significantly higher than preoperative values in group M
      (P < 0.05). CONCLUSIONS: Based on VRS, Ramsay sedation scores, and surgeon and
      anesthesiologist satisfaction scores, dexmedetomidine or midazolam combined with
      tramadol PCA provided adequate analgesia and sedation in these adult patients
      undergoing septoplasty or endoscopic sinus surgery with MAC. A significantly
      larger amount of rescue tramadol was used by group M, suggesting that a better
      analgesic effect was achieved with dexmedetomidine.

PMID- 24678122
TI  - Evaluation of the effectiveness and tolerability of controlled-release diclofenac
      potassium versus immediate-release diclofenac-potassium in the treatment of knee
      osteoarthritis.
AB  - Abstract. BACKGROUND: A controlled-release (CR) form of diclofenac-potassium has
      been developed, which delivers 100 mg over the course of 24 hours. This
      formulation is administered QD and provides steady plasmatic levels of the drug.
      OBJECTIVE: The aim of this study was to compare the effectiveness and
      tolerability of CR diclofenac-potassium versus the immediate-release (IR)
      formulation, when used for treatment of pain in patients with knee
      osteoarthritis. METHODS: This prospective, randomized, double-blind, comparative,
      multi-center, parallel-group study was conducted in male and female patients who
      had been previously diagnosed with knee osteoarthritis. Inclusion criteria
      included knee joint pain and >=3 of the following: age >50 years, morning
      rigidity lasting <30 minutes, crackling in the joint, pain with applied pressure
      to the bones, bone hypertrophy, absence of articular heat, and a radiology status
      of I to III on the Kellgren-Lawrence scale. Patients were randomly divided into 1
      of 2 equal-sized groups: 1 group received diclofenac-potassium IR 50 mg BID for
      30 days and 1 group received diclofenac-potassium CR 100 mg QD for 30 days.
      Patients were assessed at baseline and again at 15 and 30 days after initiation
      of treatment with a physical examination, pain measurement via 100-mm visual
      analog scale (VAS), and Western Ontario McMaster (WOMAC) osteoarthritis index
      questionnaire. Adverse events (AEs) were assessed by direct interrogation,
      hematology controls, blood chemistry, hepatic tests, coagulation tests, and urine
      tests performed on patients before treatment initiation and on day 30. RESULTS:
      Sixty-five patients were screened and 62 patients (mean [SD]age, 61.8 [8.9]
      years; mean [SD] weight, 71.3 [12.4] kg; female sex, 55 [88.9%]) were included in
      the study; each study group had 31 patients. After 30 days, both products were
      equally effective in relieving pain, as measured by VAS (IR, 17.3 vs CR, 21.6; P
      = NS), and changes in the WOMAC score (IR, 14.5 vs CR, 19.2; P = NS).
      Significantly more patients in the IR group reported feeling better after 30 days
      than in the CR group (94% vs 76%; P = 0.002) and, according to the physician's
      opinion, significantly more patients treated with diclofenac-potassium IR felt
      better (97% vs 83%; P = 0.03). Significantly more patients in the IR group
      required rescue medication than those in the CR group (36% vs 26%; P = 0.03). In
      the CR group, 7 patients experienced AEs: 6 were gastrointestinal (ie, pyrosis,
      epigastralgia, dyspepsia) and 1 patient experienced increased arterial pressure.
      One patient from this group discontinued treatment due to a lack of efficacy. In
      the IR group, 6 patients experienced AEs (ie, tachycardia, epigastralgia, and
      pyrosis). One patient discontinued because of AEs, and 3 withdrew due to a lack
      of efficacy. CONCLUSION: Based on the results from this small study in a
      Venezuelan population, both IR and CR formulations of diclofenac-potassium have
      similar effectiveness and tolerability profiles.

PMID- 24678123
TI  - Anti-albuminuric effect of losartan versus amlodipine in hypertensive Japanese
      patients with type 2 diabetes mellitus: A prospective, open-label, randomized,
      comparative study.
AB  - Abstract. BACKGROUND: The antiproteinuric effect of the angiotensin II receptor
      antagonist losartan has been observed in patients with type 2 diabetes mellitus
      (T2DM). Proteinuria is considered to be a predictor of the progression of kidney
      disease. OBJECTIVE: The aims of the present study were to compare and examine the
      ability of losartan and amlodipine to ameliorate albuminuria in hypertensive
      Japanese patients (systolic blood pressure >=140 mm Hg or diastolic blood
      pressure >=90 mm Hg) with T2DM and whether the change in albuminuria was
      associated with a change in glomerular filtration rate (GFR). METHODS: This
      prospective, open-label, randomized, comparative study was conducted over 3
      months at the Kinki University School of Medicine, Osaka-Sayama, Japan.
      Hypertensive patients with T2DM were enrolled and randomly assigned to 1 of 2
      study groups receiving either losartan (25-100 mg/d) or the calcium channel
      blocker amlodipine (2.5-5 mg/d). Urinary albumin excretion (UAE), creatinine
      clearance, and GFR were recorded at study initiation (baseline) and study end
      (month 3). The GFR was measured from the fractional renal accumulation of (99m)Tc
      diethylenetriaminepentaacetic acid. Adverse events (AEs) were monitored by a
      clinical research nurse during the examination. RESULTS: Fifty patients were
      asked to enroll and 38 returned the informed written consent. Thirty-five
      Japanese patients were included in the final study analysis. Seventeen patients
      were assigned to the losartan group (male sex, 10 [58.8%]; mean [SD] age, 58.1
      [8.2] years) and 18 were assigned to the amlodipine group (male sex, 10 [55.6%];
      mean [SD] age, 57.4 [8.9] years); no significant between-group difference in
      demographics was observed. A significant decrease from baseline to month 3 of
      mean (SD) UAE was observed in the losartan group (352.5 [556.6] mg/d vs 275.7
      [466.1] mg/d; P = 0.048). No significant difference in mean (SD) UAE was observed
      in the amlodipine group for the same time period (298.2 [416.6] mg/d vs 322.7
      [415.4] mg/d). There was a statistically significant difference found in the mean
      (SD) percent change of UAE from baseline to month 3 in the losartan group
      compared with the amlodipine group (-23.52 [28.42] vs +27.90 [63.51]; P = 0.004).
      Neither group was associated with a significant change in GFR during the course
      of the study. No patient discontinued the study due to AEs that were considered,
      by the investigator, to be possibly or probably associated with study treatment.
      CONCLUSIONS: Treatment with losartan, but not amlodipine, was associated with a
      reduction in albuminuria in these hypertensive Japanese patients with T2DM within
      a period as short as 3 months. Neither drug was associated with a significant
      change in GFR. Therefore, the reduction of UAE was independent of a change in the
      GFR.

PMID- 24678124
TI  - Risk factors associated with NSAID-induced upper gastrointestinal bleeding
      resulting in hospital admissions: A cross-sectional, retrospective, case series
      analysis in valencia, spain.
AB  - Abstract. BACKGROUND: NSAIDs are a significant cause of drug-related hospital
      admissions and deaths. The therapeutic effects of NSAIDs have been associated
      with the risk for developing adverse events, mainly in the gastrointestinal
      tract. OBJECTIVES: The focus of this study was to identify the most common risk
      factors associated with NSAID-induced upper gastrointestinal bleeding (UGIB)
      resulting in hospital admissions. A secondary end point was the relationship
      between use of gastroprotective treatment and relevant risk factors to NSAID
      induced UGIB in the selected population. METHODS: This study was a cross
      sectional, retrospective, case-series analysis of NSAID-induced UGIB resulting in
      hospital admission to the Requena General Hospital, Valencia, Spain, occurring
      from 1997 to 2005. International Classification of Diseases, Ninth Revision,
      Clinical Modification codes were used to identify UGIB admissions associated with
      NSAIDs. To estimate the probability of association between UGIB and the use of
      NSAIDs, the Naranjo adverse drug reaction probability was used. Patients were
      categorized as high-risk to develop UGIB if they met >=1 of the following risk
      criteria (relevant risk factors): aged >=65 years (age risk factor); peptic ulcer
      disease or NSAID gastropathy occurring in the year before their hospital
      admission (history risk factor); and concomitant use of other NSAIDs, systemic
      corticoids, oral anticoagulants, or platelet aggregation inhibitors (concomitant
      medication risk factor). Patients were categorized as candidates to use
      gastroprotections if they met >=1 of the relevant risk factors. Patients were
      categorized as users of gastroprotective treatment if they used proton pump
      inhibitors, histamine H2-receptor antagonists, or misoprostol at hospital
      admission. RESULTS: This study comprised 209 cases of NSAID-induced UGIB (129
      men, 80 women: mean [SD] age, 71.5 [13.8] years; 128 [61.2%] receiving acetyl
      salicylic acid [ASA], with 72 [34.4%] receiving low-dose [80-325 mg] ASA).
      Prevalence of relevant risk factors for UGIB were as follows: age, 158 (75.6%)
      patients; history, 37 (17.7%); and concomitant medication, 35 (16.7%). One
      hundred seventy-eight (85.2%) patients met >=1 criterion for using a
      gastroprotective agent; 28 (15.6%) were actually using one. Only the history risk
      factor was significantly associated with the use of gastroprotective treatment (P
      = 0.007; odds ratio = 3.17). CONCLUSIONS: In this study of NSAID-induced UGIB
      resulting in hospital admission, age was the most common risk factor. However,
      this criterion was not associated with the use of gastroprotective agents. A
      large number of cases were associated with the use of ASA, primarily in those
      receiving low doses. A significant lack of gastroprotective agent use was
      observed in patients who met the criteria to use them.

PMID- 24678125
TI  - Resistance of uropathogenic bacteria to first-line antibiotics in mexico city: A
      multicenter susceptibility analysis.
AB  - Abstract. BACKGROUND: Growing antibiotic resistance demands the constant
      reassessment of antimicrobial efficacy, particularly in countries with wide
      antibiotic abuse, where higher resistance prevalence is often found. Knowledge of
      resistance trends is particularly important when prescribing antibiotics
      empirically, as is usually the case for urinary tract infections (UTIs).
      Currently, in Mexico City, ampicillin, cotrimoxazole
      (trimethoprim/sulfamethoxazole), and ciprofloxacin are used as "first-line"
      antibiotic treatment for UTI. OBJECTIVE: The aim of this study was to analyze the
      resistance of bacterial isolates to antibiotics, with a focus on first-line
      antibiotics, in Mexican pediatric patients and sexually active or pregnant female
      outpatients. METHODS: In this multicenter susceptibility analysis, bacterial
      isolates from urine samples collected from pediatric patients and sexually-active
      or pregnant female outpatients presenting with acute, uncomplicated UTIs in
      Mexico City from January 2006 through June 2006, were included in the study.
      Samples were tested for susceptibility to 10 antibiotics by the disk-diffusion
      method. RESULTS: Four-hundred and seventeen bacterial isolates were derived from
      sexually active or pregnant female outpatients (324 Escherichia coli) and
      pediatric patients (93 Klebsiella pneumoniae). We found a high prevalence of
      resistance towards the drugs used as "first-line" when treating UTIs: ampicillin,
      cotrimoxazole, and ciprofloxacin (79%, 60%, and 24% resistance, respectively).
      Ninety-eight percent of K pneumoniae isolates were resistant to ampicillin,
      whereas 66% of the E coli isolates were resistant to cotrimoxazole. Resistance
      towards third-generation cephalosporins was also high (6%-8% of E coli and 10%
      28% of K pneumoniae). This was possibly caused by chromosomal beta-lactamases, as
      30% of all isolates were also resistant to amoxicillin/clavulanate. In contrast,
      98% of the E coli isolates and 84% of the K pneumoniae strains (96% of all
      isolates) were found to be susceptible to nitrofurantoin, which has been in
      clinical use for much longer than most other drugs in this study. CONCLUSION: In
      these urine samples from laboratories in Mexico City, resistance of K pneumoniae
      and E coli isolates to first-line treatment (ampicillin, cotrimoxazole, or
      ciprofloxacin) of UTI was high, whereas most E coli and K pneumoniae isolates
      were susceptible to nitrofurantoin and the fourth-generation cephalosporin
      cefepime. (Curr Ther Res Clin Exp. 2007;68:120-126) Copyright (c) 2007 Excerpta
      Medica, Inc.

PMID- 24678126
TI  - A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain
      Stimulation.
AB  - A power-efficient wireless stimulating system for a head-mounted deep brain
      stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC
      supply voltage from a constant AC power carrier utilizing phase control feedback,
      while achieving high AC-DC power conversion efficiency (PCE) through active
      synchronous switching. A current-controlled stimulator adopts closed-loop supply
      control to automatically adjust the stimulation compliance voltage by detecting
      stimulation site potentials through a voltage readout channel, and improve the
      stimulation efficiency. The stimulator also utilizes closed-loop active charge
      balancing to maintain the residual charge at each site within a safe limit, while
      receiving the stimulation parameters wirelessly from the amplitude-shift-keyed
      power carrier. A 4-ch wireless stimulating system prototype was fabricated in a
      0.5-MUm 3M2P standard CMOS process, occupying 2.25 mm2. With 5 V peak AC input at
      2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and
      4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive
      supply control increases the stimulation efficiency up to 30% higher than a fixed
      supply voltage to 58 ~ 68%. The prototype wireless stimulating system was
      verified in vitro.

PMID- 24678127
TI  - Using principles of community participatory research Groundwork for a
      collaboration in Brazil.

PMID- 24678128
TI  - THE VARIED INFLUENCE OF SES ON ENVIRONMENTAL CONCERN.
AB  - OBJECTIVE: Cross-national studies have found positive relationships of
      socioeconomic status (SES) with environmental concern at the individual level but
      have not systematically examined how the relationships may differ across nations.
      Such comparisons have relevance to identifying the generality of theories of
      postmaterialism, affluence, and global environmentalism. METHODS: This study
      specifies how the individual-level influence of SES varies across national
      contexts and tests predictions using four waves of the World Values Survey on up
      to 96 nations. RESULTS: The results show that SES is associated only weakly with
      environmental concern in lower income nations with poor environmental conditions
      but is associated strongly and positively in higher income nations with better
      environmental conditions. CONCLUSION: SES has a contingent relationship with
      environmental concern such that the global environmentalism theory receives
      support for lower income nations, while the postmaterialism and affluence
      theories receive support for higher income nations.

PMID- 24678129
TI  - Synthesis of 4-aryl-6-indolylpyridine-3-carbonitriles and evaluation of their
      antiproliferative activity.
AB  - A novel class of 6-indolypyridine-3-carbonitrilile derivatives were synthesized
      and evaluated for antiproliferative activities to establish structure-activity
      relationship. The synthesis was carried out through one-pot multicomponent
      reaction of 3-acetylindole, aromatic aldehydes, ethyl cyanoacetate, and ammonium
      acetate in the presence of piperidine as a catalyst, using a microwave
      irradiation method or a traditional thermal method. This was followed by
      chlorination for compounds 13a-e and subsequent nucleophilic substitution of the
      chlorine group by ethylenediamine at C2 position of the pyridine ring. The
      antiproliferative activity of these new nicotinonitriles was evaluated against
      human ovarian adenocarcinoma (SK-OV-3), breast adenocarcinoma (MCF-7), and cervix
      adenocarcinoma (HeLa) cells. Among all compounds, 2-((2-aminoethyl)amino)-4-aryl
      6-indolylnicotinonitriles series (15a, 15b, 15d, and 15e) exhibited higher
      antiproliferative activity cells with IC50 values of 4.1-13.4 MUM.

PMID- 24678130
TI  - Impacts of an ethanol-blended fuel release on groundwater and fate of produced
      methane: Simulation of field observations.
AB  - In a field experiment at Vandenberg Air Force Base (VAFB) designed to mimic the
      impact of a small-volume release of E10 (10% ethanol and 90% conventional
      gasoline), two plumes were created by injecting extracted groundwater spiked with
      benzene, toluene, and o-xylene, abbreviated BToX (No-Ethanol Lane) and BToX plus
      ethanol (With-Ethanol Lane) for 283 days. We developed a reactive transport model
      to understand processes controlling the fate of ethanol and BToX. The model was
      calibrated to the extensive field dataset and accounted for concentrations of
      sulfate, iron, acetate, and methane along with iron-reducing bacteria, sulfate
      reducing bacteria, fermentative bacteria, and methanogenic archaea. The benzene
      plume was about 4.5 times longer in the With-Ethanol Lane than in the No-Ethanol
      Lane. Matching this different behavior in the two lanes required inhibiting
      benzene degradation in the presence of ethanol. Inclusion of iron reduction with
      negligible growth of iron-reducers was required to reproduce the observed
      constant degradation rate of benzene. Modeling suggested that vertical dispersion
      and diffusion of sulfate from an adjacent aquitard were important sources of
      sulfate in the aquifer. Matching of methane data required incorporating initial
      fermentation of ethanol to acetate, methane loss by outgassing, and methane
      oxidation coupled to sulfate and iron reduction. Simulation of microbial growth
      using dual Monod kinetics, and including inhibition by more favorable electron
      acceptors, generally resulted in reasonable yields for microbial growth of 0.01
      0.05.

PMID- 24678132
TI  - Frailty Models for Familial Risk with Application to Breast Cancer.
AB  - In evaluating familial risk for disease we have two main statistical tasks:
      assessing the probability of carrying an inherited genetic mutation conferring
      higher risk; and predicting the absolute risk of developing diseases over time,
      for those individuals whose mutation status is known. Despite substantial
      progress, much remains unknown about the role of genetic and environmental risk
      factors, about the sources of variation in risk among families that carry high
      risk mutations, and about the sources of familial aggregation beyond major
      Mendelian effects. These sources of heterogeneity contribute substantial
      variation in risk across families. In this paper we present simple and efficient
      methods for accounting for this variation in familial risk assessment. Our
      methods are based on frailty models. We implemented them in the context of
      generalizing Mendelian models of cancer risk, and compared our approaches to
      others that do not consider heterogeneity across families. Our extensive
      simulation study demonstrates that when predicting the risk of developing a
      disease over time conditional on carrier status, accounting for heterogeneity
      results in a substantial improvement in the area under the curve of the receiver
      operating characteristic. On the other hand, the improvement for carriership
      probability estimation is more limited. We illustrate the utility of the proposed
      approach through the analysis of BRCA1 and BRCA2 mutation carriers in the
      Washington Ashkenazi Kin-Cohort Study of Breast Cancer.

PMID- 24678131
TI  - A Sulfide-Bridged Diiron(II) Complex with a cis-N2H4Ligand.
AB  - A sulfide-bridged diiron(II) complex bearing a cis-N2H4 (hydrazine) ligand has
      been prepared by reaction of LFeII(MU-S)FeIIL (1; L = sterically encumbered
      betadiketiminate ligand) with 2 molar equivalents of N2H4. The metastable
      diiron(II) hydrazine complex LFeII(MU-S)(MUH N-NH2)FeII (3) is formed, as shown
      by crystallography, and NMR, vibrational, and electronic absorption
      spectroscopies. Compound 3 has been crystallographically characterized as its DBU
      (1,8-diazabicyclo[5.4.0]undec-7$ene) adduct, which exhibits weak N-H...DBU
      hydrogen bonding. The synthetic process evolves roughly 2 equivalents of NH3. The
      cis-N2H4 bridge in 3 may be relevant to the structure and function of
      intermediates on the FeMoco of nitrogenase.

PMID- 24678133
TI  - A locally convoluted cluster model for nucleosome positioning signals in chemical
      map.
AB  - Nucleosome is the fundamental packing unit of DNA in eukaryotic cells, and its
      positioning plays a critical role in regulation of gene expression and chromosome
      functions. Using a recently developed chemical mapping method, nucleosomes can be
      potentially mapped with an unprecedented single-base-pair resolution. Existence
      of overlapping nucleosomes due to cell mixture or cell dynamics, however, causes
      convolution of nucleosome positioning signals. In this paper, we introduce a
      locally convoluted cluster model and a maximum likelihood deconvolution approach,
      and illustrate the effectiveness of this approach in quantification of the
      nucleosome positional signal in the chemical mapping data.

PMID- 24678134
TI  - Some Statistical Strategies for DAE-seq Data Analysis: Variable Selection and
      Modeling Dependencies among Observations.
AB  - In DAE (DNA After Enrichment)-seq experiments, genomic regions related with
      certain biological processes are enriched/isolated by an assay and are then
      sequenced on a high-throughput sequencing platform to determine their genomic
      positions. Statistical analysis of DAE-seq data aims to detect genomic regions
      with significant aggregations of isolated DNA fragments ("enriched regions")
      versus all the other regions ("background"). However, many confounding factors
      may influence DAE-seq signals. In addition, the signals in adjacent genomic
      regions may exhibit strong correlations, which invalidate the independence
      assumption employed by many existing methods. To mitigate these issues, we
      develop a novel Autoregressive Hidden Markov Model (AR-HMM) to account for
      covariates effects and violations of the independence assumption. We demonstrate
      that our AR-HMM leads to improved performance in identifying enriched regions in
      both simulated and real datasets, especially in those in epigenetic datasets with
      broader regions of DAE-seq signal enrichment. We also introduce a variable
      selection procedure in the context of the HMM/AR-HMM where the observations are
      not independent and the mean value of each state-specific emission distribution
      is modeled by some covariates. We study the theoretical properties of this
      variable selection procedure and demonstrate its efficacy in simulated and real
      DAE-seq data. In summary, we develop several practical approaches for DAE-seq
      data analysis that are also applicable to more general problems in statistics.

PMID- 24678135
TI  - Feature Selection for Varying Coefficient Models With Ultrahigh Dimensional
      Covariates.
AB  - This paper is concerned with feature screening and variable selection for varying
      coefficient models with ultrahigh dimensional covariates. We propose a new
      feature screening procedure for these models based on conditional correlation
      coefficient. We systematically study the theoretical properties of the proposed
      procedure, and establish their sure screening property and the ranking
      consistency. To enhance the finite sample performance of the proposed procedure,
      we further develop an iterative feature screening procedure. Monte Carlo
      simulation studies were conducted to examine the performance of the proposed
      procedures. In practice, we advocate a two-stage approach for varying coefficient
      models. The two stage approach consists of (a) reducing the ultrahigh
      dimensionality by using the proposed procedure and (b) applying regularization
      methods for dimension-reduced varying coefficient models to make statistical
      inferences on the coefficient functions. We illustrate the proposed two-stage
      approach by a real data example.

PMID- 24678136
TI  - Evidence for Priming Across Intervening Sentences During On-Line Sentence
      Comprehension.
AB  - Three experiments investigated factors contributing to syntactic priming during
      on-line comprehension. In all of the experiments, a prime sentence containing a
      reduced relative clause was presented prior to a target sentence that contained
      the same structure. Previous studies have shown that people respond more quickly
      when a syntactically related prime sentence immediately precedes a target. In the
      current study, ERP and eyetracking measures were used to assess whether priming
      in sentence comprehension persists when one or more unrelated filler sentences
      appear between the prime and the target. In experiment 1, a reduced P600 was
      found to target sentences both when there were no intervening unrelated fillers,
      and when there was one unrelated filler between the prime and the target. Thus,
      processing the prime sentence facilitated processing of the syntactic form of the
      target sentence. Experiments 2 and 3, eye-tracking experiments, showed that
      target sentence processing was facilitated when three filler sentences intervened
      between the prime and the target. These experiments show that priming effects in
      comprehension can be observed when unrelated material appears after a prime
      sentence and before the target. We interpret the results with respect to residual
      activation and implicit learning accounts of priming.

PMID- 24678137
TI  - Coefficient of Variation, Signal-to-Noise Ratio, and Effects of Normalization in
      Validation of Biomarkers from NMR-based Metabonomics Studies.
AB  - A primary goal of metabonomics research is biomarker discovery for human diseases
      based on differences in metabolic profiles between healthy and diseased patient
      populations. One of the most significant challenges in biomarker discovery is
      validation, which implicitly depends on the coefficient of variation (CV)
      associated with the measurement technique. This paper investigates how the CV of
      metabolite resonances measured by nuclear magnetic resonance spectroscopy (NMR)
      depends on signal-to-noise ratio (SNR) and normalization method. CVs were
      calculated for NMR resonance peaks in a series of NMR spectra of five synthetic
      urine samples collected over an eight-month period. An inverse correlation was
      detected between SNR and CV for all normalization methods. Small peaks with
      SNR<15 tended to have larger CVs (15-30%) compared to peaks with the highest
      SNR>150, which typically had smaller CVs (5-10%). The inverse relationship
      between CV and SNR roughly obeyed a log10 dependence. Quotient normalization (QN)
      tended to produce smaller CVs for smaller peaks, but larger CVs for the strongest
      peaks in the data, compared to no normalization, normalization to total intensity
      (NTI) or normalization to an internal standard (NIS). Consequently, quotient
      normalization appears optimal for validating low concentration metabolites. NTI
      or NIS appear superior to QN for samples that have very small variation in total
      signal intensity. While the inverse relationship between CV and log10(SNR) did
      not strictly hold for all metabolites, weaker concentration metabolites will
      likely require more rigorous validation as potential biomarkers since they tend
      to have poorer reproducibility.

PMID- 24678138
TI  - Particle Count Statistics Applied to the Penetration of a Filter Challenged with
      Nanoparticles.
AB  - Statistical confidence in a single measure of filter penetration (P) is dependent
      on the low number of particle counts made downstream of the filter. This paper
      discusses methods for determining an upper confidence limit (UCL) for a single
      measure of penetration. The magnitude of the UCL was then compared to the P
      value, UCL <= 2P, as a penetration acceptance criterion (PAC). This statistical
      method was applied to penetration trials involving an N95 filtering facepiece
      respirator challenged with sodium chloride and four engineered nanoparticles:
      titanium dioxide, iron oxide, silicon dioxide and single-walled carbon nanotubes.
      Ten trials were performed for each particle type with the aim of determining the
      most penetrating particle size (MPPS) and the maximum penetration, Pmax. The PAC
      was applied to the size channel containing the MPPS. With those P values that met
      the PAC for a given set of trials, an average Pmax and MPPS was computed together
      with corresponding standard deviations. Because the size distribution of the
      silicon dioxide aerosol was shifted towards larger particles relative to the
      MPPS, none of the ten trials satisfied the PAC for that aerosol. The remaining
      four particle types resulted in at least 4 trials meeting the criterion. MPPS
      values ranged from 35 - 53 nm with average Pmax values varying from 4.0% for
      titanium dioxide to 7.0% for iron oxide. The use of the penetration acceptance
      criterion is suggested for determining the reliability of penetration
      measurements obtained to determine filter Pmax and MPPS.

PMID- 24678139
TI  - Oviposition habitat selection by container-dwelling mosquitoes: responses to cues
      of larval and detritus abundances in the field.
AB  - Insects' oviposition responses to resource and larval densities can be important
      factors determining distributions and competitive interactions of larvae. Aedes
      albopictus (Skuse) and Aedes aegypti (L.) (Diptera: Culicidae) show aggregated
      distributions of larvae in the field, larval interactions that are affected by
      detritus resources, and oviposition responses to resource and density cues in the
      laboratory. We conducted field experiments testing whether these species choose
      oviposition sites in response to chemical cues indicating detritus resource
      quantity and quality or larval abundances.In experiment 1, both species showed
      interactive responses to water conditioned with high or low quantities of
      senescent live oak leaves and density combinations of A. albopictus and A.
      aegypti larvae. Aedes aegypti preferred high-detritus containers when
      conspecifics were absent. Aedes albopictus tended to prefer high-detritus
      containers when larval density was low. We found no evidence of interspecific
      differences in oviposition preferences.In experiment 2, A. albopictus preferred
      high detritus over low or no detritus, and rapidly-decaying, high-quality
      detritus over low-quality detritus.Oviposition choices by these Aedes are mainly
      determined by resource quantity and quality, with larval densities having minor,
      variable effects. Oviposition responses of these species are unlikely to lead to
      resource partitioning. Aggregated distributions of these species in the field are
      unlikely to be products of oviposition choices based on larval densities.

PMID- 24678140
TI  - Combustion of Biosolids in a Bubbling Fluidized Bed, Part 1: Main Ash-Forming
      Elements and Ash Distribution with a Focus on Phosphorus.
AB  - This is the first in a series of three papers describing combustion of biosolids
      in a 5-kW bubbling fluidized bed, the ash chemistry, and possible application of
      the ash produced as a fertilizing agent. This part of the study aims to clarify
      whether the distribution of main ash forming elements from biosolids can be
      changed by modifying the fuel matrix, the crystalline compounds of which can be
      identified in the raw materials and what role the total composition may play for
      which compounds are formed during combustion. The biosolids were subjected to low
      temperature ashing to investigate which crystalline compounds that were present
      in the raw materials. Combustion experiments of two different types of biosolids
      were conducted in a 5-kW benchscale bubbling fluidized bed at two different bed
      temperatures and with two different additives. The additives were chosen to
      investigate whether the addition of alkali (K2CO3) and alkaline-earth metal
      (CaCO3) would affect the speciation of phosphorus, so the molar ratios targeted
      in modified fuels were P:K = 1:1 and P:K:Ca = 1:1:1, respectively. After
      combustion the ash fractions were collected, the ash distribution was determined
      and the ash fractions were analyzed with regards to elemental composition (ICP
      AES and SEM-EDS) and part of the bed ash was also analyzed qualitatively using
      XRD. There was no evidence of zeolites in the unmodified fuels, based on low
      temperature ashing. During combustion, the biosolid pellets formed large bed ash
      particles, ash pellets, which contained most of the total ash content (54%-95%
      (w/w)). This ash fraction contained most of the phosphorus found in the ash and
      the only phosphate that was identified was a whitlockite, Ca9(K,Mg,Fe)(PO4)7, for
      all fuels and fuel mixtures. With the addition of potassium, cristobalite (SiO2)
      could no longer be identified via X-ray diffraction (XRD) in the bed ash
      particles and leucite (KAlSi2O6) was formed. Most of the alkaline-earth metals
      calcium and magnesium were also found in the bed ash. Both the formation of
      aluminum-containing alkali silicates and inclusion of calcium and magnesium in
      bed ash could assist in preventing bed agglomeration during co-combustion of
      biosolids with other renewable fuels in a full-scale bubbling fluidized bed.

PMID- 24678141
TI  - Iterative graph cuts for image segmentation with a nonlinear statistical shape
      prior.
AB  - Shape-based regularization has proven to be a useful method for delineating
      objects within noisy images where one has prior knowledge of the shape of the
      targeted object. When a collection of possible shapes is available, the
      specification of a shape prior using kernel density estimation is a natural
      technique. Unfortunately, energy functionals arising from kernel density
      estimation are of a form that makes them impossible to directly minimize using
      efficient optimization algorithms such as graph cuts. Our main contribution is to
      show how one may recast the energy functional into a form that is minimizable
      iteratively and efficiently using graph cuts.

PMID- 24678142
TI  - Computationally Efficient Steady-State Solution of the Bloch Equations for Rapid
      Sinusoidal Scans Based on Fourier Expansion in Harmonics of the Scan Frequency.
AB  - Rapid-scan EPR has been shown to improve the signal-to-noise ratio relative to
      conventional continuous wave spectroscopy. Equations are derived for the steady
      state solution to the Bloch equations as a Fourier expansion in the harmonics of
      the scan frequency. This simulation method is about two orders of magnitude
      faster than time-domain numerical integration.

PMID- 24678144
TI  - Hyponatremia in the critically ill: Time for a change.

PMID- 24678145
TI  - Hospital acquired invasive group A streptococcus infections.

PMID- 24678143
TI  - Feasibility of Direct Digital Sampling for Diffuse Optical Frequency Domain
      Spectroscopy in Tissue.
AB  - Frequency domain optical spectroscopy in the diffusive regime is currently being
      investigated for biomedical applications including tumor detection, therapy
      monitoring, exercise metabolism, and others. Analog homodyne or heterodyne
      detection of sinusoidally modulated signals have been the predominant method for
      measuring phase and amplitude of photon density waves that have traversed through
      tissue. Here we demonstrate the feasibility of utilizing direct digital sampling
      of modulated signals using a 3.6 Gigasample/second 12 bit Analog to Digital
      Converter. Digitally synthesized modulated signals between 50MHz and 400MHz were
      measured on tissue simulating phantoms at six near-infrared wavelengths. An
      amplitude and phase precision of 1% and 0.6 degrees were achieved during drift
      tests. Amplitude, phase, scattering and absorption values were compared with a
      well-characterized network analyzer based diffuse optical device. Measured
      optical properties measured with both systems were within 3.6% for absorption and
      2.8% for scattering over a range of biologically relevant values. Direct digital
      sampling represents a viable method for frequency domain diffuse optical
      spectroscopy and has the potential to reduce system complexity, size, and cost.

PMID- 24678146
TI  - Preventability of death in a medical ICU in a developing country.

PMID- 24678147
TI  - Tropical fevers: Management guidelines.
AB  - Tropical fevers were defined as infections that are prevalent in, or are unique
      to tropical and subtropical regions. Some of these occur throughout the year and
      some especially in rainy and post-rainy season. Concerned about high prevalence
      and morbidity and mortality caused by these infections, and overlapping clinical
      presentations, difficulties in arriving at specific diagnoses and need for early
      empiric treatment, Indian Society of Critical Care Medicine (ISCCM) constituted
      an expert committee to develop a consensus statement and guidelines for
      management of these diseases in the emergency and critical care. The committee
      decided to focus on most common infections on the basis of available
      epidemiologic data from India and overall experience of the group. These included
      dengue hemorrhagic fever, rickettsial infections/scrub typhus, malaria (usually
      falciparum), typhoid, and leptospira bacterial sepsis and common viral infections
      like influenza. The committee recommends a 'syndromic approach' to diagnosis and
      treatment of critical tropical infections and has identified five major clinical
      syndromes: undifferentiated fever, fever with rash / thrombocytopenia, fever with
      acute respiratory distress syndrome (ARDS), fever with encephalopathy and fever
      with multi organ dysfunction syndrome. Evidence based algorithms are presented to
      guide critical care specialists to choose reliable rapid diagnostic modalities
      and early empiric therapy based on clinical syndromes. 

PMID- 24678148
TI  - Clinical outcomes after utilizing surviving sepsis campaign in children with
      septic shock and prognostic value of initial plasma NT-proBNP.
AB  - BACKGROUND AND OBJECTIVE: The surviving sepsis campaign treatment guideline (SSC)
      implementation is associated with improved outcome in adults with severe sepsis.
      The effect on outcome of pediatric sepsis is less clear. PURPOSE: To determine
      the clinical outcomes of SSC implementation and to investigate the prognostic
      value of initial plasma NT-proBNP and procalcitonin in children. MATERIALS AND
      METHODS: Infants and children (aged 1month/0-15 years with severe sepsis or
      septic shock) were prospectively enrolled and treated according to the
      guidelines. Initial blood drawn was saved for NT-pro-BNP, procalcitonin
      measurements and clinical data were also recorded. RESULTS: A total of 47
      subjects were recruited. Since the application of the SSC, our mortality rate had
      significantly decreased from 42-19% (P = 0.003) as compared to the data in the
      previous 3 years. Clinical factors that significantly increased the mortality
      rate were: Initial central venous oxygen saturation < 7 0% after fluid
      resuscitation [odds ratio (OR) = 23.3; 95% confidence interval (CI) 3.7-143; P =
      0.001], and initial albumin level (<= 3 g/dl, OR = 6.7; 95% CI 1.2-37.5, P =
      0.03). There was asignificant difference between the initial NT-proBNP levels
      between survivors and non survivors, (6280.3 +/- 9597 ng/L, P < 0.001), but not
      for procalcitonin (12.7 +/- 24.8, 29.3 +/- 46 MUg/L, P = 0.1), respectively. An
      initial NT-proBNP level of more than 11,200 pg/ml predicted Pediatric Intensive
      Care Unit (PICU) mortality with a sensitivity of 85.7% and a specificity of 90%.
      CONCLUSIONS: A modified SSC for severe sepsis and septic shock significantly
      reduced the mortality rate in our PICU. High initial NT-ProBNP level was
      associated with mortality.

PMID- 24678149
TI  - Outbreak of Streptococcus pyogenes emm type 58 in a high dependency unit of a
      level-1 trauma center of India.
AB  - BACKGROUND AND AIMS: Group A Streptococcus (GAS) can cause illnesses ranging from
      self-limited to severe, life-threatening, invasive infections. The objective of
      the following study was to investigate a suspected Streptococcus pyogenes
      outbreak in a high dependency unit (HDU) of our trauma center. MATERIALS AND
      METHODS: All the isolates of beta hemolytic Streptococci were identified by
      standard microbiological methods, Vitek 2 system and latex agglutination tests.
      Antimicrobial susceptibility testing was performed as recommended by Clinical
      Laboratory Standards Institute. Exotoxin genes, including speA, speB, speC, speF,
      smeZ, ssa, speG, speH, speJ, speL, speM and speI were detected by polymerase
      chain reaction (PCR). The emm types of isolates of S. pyogenes were determined by
      sequencing the variable 5' end of emm gene after amplification by PCR. RESULTS:
      In a 28 bedded poly-trauma ward with a four bedded HDU three out of four patients
      developed S. pyogenes emm type 58 infection. The strain was macrolide and
      tetracycline resistant and produced the Streptococcal pyrogenic exotoxins speB,
      speC, speG, speF and smeZ. Surveillance sampling was done for investigation from
      patients, health-care workers and environmental samples. CONCLUSION: An outbreak
      of GAS infections was established caused by the uncommonly reported emm type 58.
      The outbreak was controlled by prompt treatment, intensive surveillance, feedback
      and training.

PMID- 24678150
TI  - Hyponatremia in critically ill patients.
AB  - CONTEXT: Hyponatremia is a common electrolyte disturbance in critically ill hence
      understanding its implications is important. AIMS: This study was carried out to
      ascertain frequency, predisposing conditions and outcome in critically ill
      patients with hyponatremia on intensive care unit (ICU) admission. SETTINGS AND
      DESIGN: This was an observational, prospective study of a series of ICU patients
      during a 12-month period. MATERIALS AND METHODS: THE PATIENTS WERE DIVIDED INTO
      TWO GROUPS: Hyponatremic (serum sodium < 135 mmol/L) and Eunatremic groups (135
      145 mmol/L). Clinical examination included volume status and drug history,
      biochemistries, clinical diagnosis and cause of hyponatremia. STATISTICAL
      ANALYSIS USED: Fisher's exact test, unpaired t-tests Wilcoxon ranksum tests,
      profile-likelihood method, log-rank test and Kaplan-Meier curves were used. P <
      0.05 were considered to be statistically significant. RESULTS: In the
      hyponatremic group, the frequency of hyponatremia on ICU admission was 34.3%,
      most were euvolumic, 58.96%. Females comprised of 36.5%. The mean age was 60.4 +/
      17.2. The Syndrome of inappropriate Antidiuretic Hormone (SIADH) criteria was
      met in ninety-one patients (36.25%), peumonia being the leading cause of SIADH.
      Patients with severe sepsis, elective surgery patients, renal failure and heart
      failure, cirrhosis of liver and subarachnoid hemorrhage were other more likely
      etiologic causes (P < 0.05). The hyponatremic group spent a longer time in the
      ICU (P = 0.02), had longer mechanical ventilator days (P < 0.05) and had an
      increased mortality rate (P = 0.01). CONCLUSIONS: Hyponatremia present on
      admission to the ICU is independent risk factors for poor prognosis.

PMID- 24678151
TI  - Preventability of death in a medical intensive care unit at a university hospital
      in a developing country.
AB  - OBJECTIVE: To determine the incidence and characteristics of preventable in-ICU
      deaths. MATERIALS AND METHODS: A one-year observational study was conducted in a
      medical ICU of a teaching hospital. All patients who died in medical ICU beyond
      24 h were analyzed and reviewed during daily medical meeting. A death was
      considered preventable when it would not have occurred if the patient had
      received ordinary standards of care appropriate for the time of study.
      Preventability of death was classified by using a 1-6 point preventability scale.
      The types of medical errors causing preventable in-ICU deaths and the
      contributory factors to deaths were identified. RESULTS: 120 deaths (47 +/- 19
      years, 57 months-63 weeks) were analyzed (mortality: 23%; 95% confidence interval
      (CI):15-31%). At admission, Acute Physiology and Chronic Health Evaluation
      (APACHE) II score was 18 +/- 7.6 and Charlson comorbidity index was 1.3 +/- 1.6.
      The main diagnosis was infectious disease (57%) and respiratory disease (23%).
      The median period between the ICU admission and death was 5 days. The rate of
      preventable in-ICU deaths was 14.1% (17/120). The most common medical errors
      related to occurrence of preventable in-ICU deaths were therapeutic error (52.9%)
      and inappropriate technical procedure (23.5%). The preventable in-ICU deaths were
      associated with inadequate training or supervision of clinical staff (58.8%), no
      protocol (47.1%), inadequate functioning of hospital departments (29.4%),
      unavailable equipment (23.5%), and inadequate communication (17.6%). CONCLUSION:
      According to our study, one to two in-ICU deaths would be preventable per month.
      Our results suggest that the implementation of supervision and protocols could
      improve outcomes for critically ill patients.

PMID- 24678153
TI  - Delayed onset neuropathy along with recurrent laryngeal nerve palsy due to
      organophosphate poisoning and the role of physiotherapy rehabilitation.
AB  - Organophosphorus poisoning is a major global cause of health problems and the
      leading cause of mortality and morbidity in the developing countries. In this,
      the inhibition of acetyl-choline esterase and neurotoxic esterase along with
      nicotinic receptor involvement produces three well-identified and documented
      clinical phases: The initial cholinergic phase, which is a medical emergency
      often requiring management in an intensive care unit; the intermediate syndrome,
      during which prolonged ventilator care is necessary; and finally delayed
      neurotoxicity. Vocal cord paralysis is rare and leads to aphonia. Role of
      physiotherapy rehabilitation is substantial in all three stages and aims at early
      weaning off from mechanical ventilator until the functional independence and
      community integration of the patient. 

PMID- 24678152
TI  - Intensive care unit acquired weakness in children: Critical illness
      polyneuropathy and myopathy.
AB  - BACKGROUND AND AIMS: Intensive care unit acquired weakness (ICUAW) is a common
      occurrence in patients who are critically ill. It is most often due to critical
      illness polyneuropathy (CIP) or to critical illness myopathy (CIM). ICUAW is
      increasingly being recognized partly as a consequence of improved survival in
      patients with severe sepsis and multi-organ failure, partly related to commonly
      used agents such as steroids and muscle relaxants. There have been occasional
      reports of CIP and CIM in children, but little is known about their prevalence or
      clinical impact in the pediatric population. This review summarizes the current
      understanding of pathophysiology, clinical presentation, diagnosis and treatment
      of CIP and CIM in general with special reference to published literature in the
      pediatric age group. SUBJECTS AND METHODS: Studies were identified through
      MedLine and Embase using relevant MeSH and Key words. Both adult and pediatric
      studies were included. RESULTS: ICUAW in children is a poorly described entity
      with unknown incidence, etiology and unclear long-term prognosis. CONCLUSIONS:
      Critical illness polyneuropathy and myopathy is relatively rare, but clinically
      significant sequelae of multifactorial origin affecting morbidity, length of
      intensive care unit (ICU) stay and possibly mortality in critically ill children
      admitted to pediatric ICU.

PMID- 24678154
TI  - Coiling of central venous catheter in the left subclavian vein, a rare
      complication.
AB  - Invasive monitoring is the need of the hour in today's scenario in intensive care
      units and perioperatively in hemodynamically unstable patients. Despite careful
      placement using proper landmarks and USG guided methods central venous
      canuulation (CVC) is associated sometimes with unforeseen complications. We
      report a rare complication of coiling of CVC in the left subclavian vein. 

PMID- 24678155
TI  - Acute pancreatitis induced thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown cause
      with an estimated incidence of one case per million. The disease is characterized
      by a pentad of symptoms: Thrombocytopenia, microangiopathic hemolytic anemia,
      neurologic changes, renal dysfunction, and fever. It causes thrombosis in the
      microvasculature of several organs, producing diverse manifestations. Acute
      pancreatitis (AP) is a well-described consequence of TTP. Acute pancreatitis
      triggering TTP is uncommon. 

PMID- 24678156
TI  - Spontaneous splenic rupture: A rare presentation of dengue fever.
AB  - Spontaneous rupture of the spleen with hemoperitoneum is a very rare, but serious
      manifestation of dengue fever (DF). We report a case of a young female who was
      presented with atraumatic abdominal pain, hypovolemic shock, anemia, ascites and
      hepatosplenomegaly with a recent history of a febrile illness. Subsequent
      investigations proved the presence of hemoperitoneum with spontaneous splenic
      rupture with seropositivity for DF. Early diagnosis and conservative management
      in this case resulted in a favorable outcome. 

PMID- 24678157
TI  - Severe methemoglobinemia due to insecticide poisoning.
AB  - Methemoglobinemia is an altered state of hemoglobin resulting in impaired oxygen
      delivery to the tissues. Deliberate ingestion of certain insecticides and
      pesticides may result in this condition. We report a case of severe
      methemoglobinemia after deliberate ingestion of an insecticide marketed to be
      safe and containing only biological extracts and fillers. Methemoglobinemia
      should be suspected with low oxygen saturation on pulse oxymetry and the presence
      of chocolate colored blood. The methemoglobin level of 91% in our patient is the
      highest level reported among methemoglobinemia survivors. 

PMID- 24678158
TI  - Acute methemoglobinemia with hemolytic anemia following bio-organic plant
      nutrient compound exposure: Two case reports.
AB  - Two young women, were reffered to our hospital on two different occasions with
      history of breathlessness and mental confusion, following consumption of two
      different bio-organic plant nutrient compounds with a suicidal intent. On
      examination, they had cyanotic mucous membranes, and their blood samples showed
      the classic 'dark chocolate brown' appearance. Work up revealed cyanosis
      unresponsive to oxygen supplementation and absence of cardiopulmonary
      abnormality. Pulse oximetry revealed saturation of 75% in case 1 and 80% in case
      2, on 8 liters oxygen supplementation via face masks, although their arterial
      blood gas analysis was normal, suggestive of "saturation gap". Methemoglobinemia
      was suspected based on these findings and was confirmed by Carbon monoxide
      oximetry (CO-oximetry). Methylene blue was administered and the patients showed
      dramatic improvement. Both the patients developed evidence of hemolysis
      approximately 72 hours following admission which improved with blood transfusion
      and supportive treatment. The patients were eventually discharged without any
      neurological sequalae. 

PMID- 24678160
TI  - Revisiting opioid overdose induced acute respiratory distress syndrome.

PMID- 24678159
TI  - Acute myocardial infarction and cocaine toxicity: One step closer.

PMID- 24678161
TI  - Angiographic catheter as airway exchange device through laryngeal airway mask in
      unanticipated difficult airway in emergency department.

PMID- 24678162
TI  - Malnutrition in a tertiary care hospital.

PMID- 24678163
TI  - Metabolic alkalosis: A less appreciated side effect of Imipenem-cilastin use
      comment.

PMID- 24678164
TI  - Nucleic acid testing-benefits and constraints.

PMID- 24678165
TI  - Mixed field agglutination: Unusual causes and serological approach.

PMID- 24678166
TI  - Autoimmune hemolytic anemia: From lab to bedside.
AB  - Autoimmune hemolytic anemia (AIHA) is not an uncommon clinical disorder and
      requires advanced, efficient immunohematological and transfusion support. Many
      AIHA patients have underlying disorder and therefore, it is incumbent upon the
      clinician to investigate these patients in detail, as the underlying condition
      can be of a serious nature such as lymphoproliferative disorder or connective
      tissue disorder. Despite advances in transfusion medicine, simple
      immunohematological test such as direct antiglobulin test (DAT) still remains the
      diagnostic hallmark of AIHA. The sensitive gel technology has enabled the
      immunohematologist not only to diagnose serologically such patients, but also to
      characterize red cell bound autoantibodies with regard to their class, subclass
      and titer in a rapid and simplified way. Detailed characterization of
      autoantibodies is important, as there is a relationship between in vivo hemolysis
      and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G
      subclass and titer. Transfusing AIHA patient is a challenge to the
      immunohematologist as it is encountered with difficulties in ABO grouping and
      cross matching requiring specialized serological tests such as alloadsorption or
      autoadsorption. At times, it may be almost impossible to find a fully matched
      unit to transfuse these patients. However, transfusion should not be withheld in
      a critically ill patient even in the absence of compatible blood. The "best
      match" or "least incompatible units" can be transfused to such patients under
      close supervision without any serious side-effects. All blood banks should have
      the facilities to perform the necessary investigations required to issue "best
      match" packed red blood cells in AIHA. Specialized techniques such as elution and
      adsorption, which at times are helpful in enhancing blood safety in AIHA should
      be established in all transfusion services. 

PMID- 24678167
TI  - Factors in enhancing blood safety by nucleic acid technology testing for human
      immunodeficiency virus, hepatitis C virus and hepatitis B virus.
AB  - In the last few decades through an awareness of transfusion transmitted
      infections (TTI), a majority of countries have mandated serology based blood
      screening assays for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV),
      and Hepatitis B virus (HBV). However, despite improved serology assays, the
      transfusion transmission of HIV, HCV, and HBV continues, primarily due to release
      of serology negative units that are infectious because of the window period (WP)
      and occult HBV infections (OBI). Effective mode of nucleic acid technology (NAT)
      testing of the viruses can be used to minimize the risk of TTIs. This review
      compiles the examples of NAT testing failures for all three viruses; analyzes the
      causes for failure, and the suggestions from retrospective studies to minimize
      such failures. The results suggest the safest path to be individual donation
      testing (ID) format for highest sensitivity, and detection of multiple regions
      for rapidly mutating and recombining viruses. The role of blood screening in the
      context of the donation and transfusion practices in India, the donor population,
      and the epidemiology is also discussed. World wide, as the public awareness of
      TTIs increases, as the recipient rights for safe blood are legally upheld, as the
      possibility to manage diseases such as hepatitis through expensive and prolonged
      treatment becomes accessible, and the societal responsibility to shoulder the
      health costs as in the case for HIV becomes routine, there is much to gain by
      preventing infections than treating diseases. 

PMID- 24678168
TI  - Hepatitis C virus: Screening, diagnosis, and interpretation of laboratory assays.
AB  - An estimated 3% of the world population is infected with Hepatitis C virus (HCV),
      a hepatotropic RNA virus, transmitted primarily via the blood route. The major
      modes of transmission of the virus include injection drug use, unsafe injection
      practices, blood transfusion etc. HCV causes chronic hepatitis in about 80% of
      those infected by it. The mainstay in diagnosing infection with HCV is to
      initially screen high risk groups for antibodies to HCV (anti-HCV). The inclusion
      of serum to cut-off ratio (S/CO) in recent guidelines is helpful in deciding the
      supplemental assay to be used to confirm initially reactive screening results.
      Nucleic acid amplification tests (NAT) are used as confirmatory tools, and also
      to determine viral load prior to initiating treatment. Quantitative NAT has
      replaced qualitative assays. Genotyping is an important tool in clinical
      management to predict the likelihood of response and determine the optimal
      duration of therapy. The impact of this infection has begun to emerge in India.
      The problem of professional blood donation despite an existing law against it,
      and flourishing unsafe injection practices, are potential sources for the spread
      of hepatitis C in our country. All health care practitioners need to understand
      how to establish or exclude a diagnosis of HCV infection and to interpret the
      tests correctly. In the absence of a preventive or therapeutic vaccine, and also
      of post-exposure prophylaxis against the virus, it is imperative to diagnose
      infection by HCV so as to prevent hepatic insult and the ensuing complications
      that follow, including primary hepatocellular carcinoma (HCC). This review aims
      to help blood bank staff regarding options for diagnosis and management of donors
      positive for HCV. 

PMID- 24678169
TI  - Sensitivity of individual and mini-pool nucleic acid testing assessed by dilution
      of hepatitis B nucleic acid testing yield samples.
AB  - INTRODUCTION: For nucleic acid testing (NAT) of blood donations, either the blood
      samples can be pooled together in a batch of six or eight prior to testing (mini
      pool-NAT [MP-NAT]), or the tests can be run on every individual sample
      (individual donor-NAT [ID-NAT]). It has been debated in various studies whether
      pooling of samples results in decreased sensitivity of detection as the volume of
      individual samples gets lesser in a pool. The objective of this study was to
      investigate the effect of dilution on the sensitivity of tests. MATERIALS AND
      METHODS: The study was performesd on nine plasma samples which were hepatitis B
      reactive exclusively by Procleix Ultrio Plus and not by Procleix Ultrio or
      serology. These nine exclusive UltrioPlus ID-NAT yield samples were diluted in
      1:2, 1:4. 1:6 and 1:8 dilutions using previously tested negative plasma and each
      dilution of every sample along with archived undiluted sample were retested in
      three replicates with Procleix Ultrio Plus Assay. RESULTS: Among NAT yield
      samples, 88.88% of the samples were detected when retested in ID-NAT in undiluted
      form. Samples with higher viral load (sample 5 and 6) were detected by all
      dilutions. When samples with viral load below 20 IU/mL were tested in dilutions
      of 1:6 or 1:8, only 9 out of 27 replicates (33.33%) were detected. This means
      that more than 67% of low viral load samples were missed by MP-NAT of 1:6 or 1:8
      dilution out of total NAT yield samples. CONCLUSION: Individual Donor NAT is
      ideal methodology for NAT as dilution due to pooling may miss samples with low
      viral load as evident in this study.

PMID- 24678170
TI  - Hepatitis E seroprevalence among blood donors: A pilot study from Western India.
AB  - BACKGROUND: Hepatitis E virus (HEV) is emerging as a potential threat to blood
      safety after several cases of transmission by transfusion or transplantation have
      been described. Currently, blood donors in India are not screened for HEV. The
      studies conducted on HEV in recent times in India have focused on epidemiology
      and future perspectives, but there is no published study on blood donors. To
      address possible issues surrounding blood safety and risk of HEV transmission
      within the Indian blood supply, HEV seroprevalence study was conducted in blood
      donors at our center. MATERIALS AND METHODS: A total of 460 male voluntary blood
      donors were selected for the study and after taking their written consent. Serum
      anti-HEV IgM was detected by Dia.Pro HEV kit (Diagnostic Bioprobes Srl, Milano,
      Italy). RESULTS: The study population was composed of 460 male voluntary blood
      donors and their age ranged from 18 to 60 years with a mean age of 30.48 years.
      Out of 460 donors, 22 (4.78%) donors were tested positive for IgM anti-HEV and
      the mean value alanine aminotransferase (ALT) was 26.06 IU/L, the highest being
      93.5 IU/L. Normal reference value of ALT in our center was 40 IU/L. Out of 22
      anti-HEV positive donors, 19 (86.36%) had ALT values above 40 IU/L. CONCLUSION:
      HEV seroprevalence of 4.78% in our center. Though reports of HEV transmission
      through blood has been reported from various parts of the world, before making it
      as a mandatory screening test among blood donors in India, further studies with
      confirmatory assay of HEV need to be done.

PMID- 24678171
TI  - Hepatitis C virus genotypes among multiply transfused hemoglobinopathy patients
      from Northern Iraq.
AB  - BACKGROUND AND AIM: Owing to the scarcity of data on hepatitis C virus (HCV)
      genotypes in Iraq and due to their epidemiological as well as therapy
      implications, this study was initiated aiming at determining these genotypes in
      Northern Iraq. MATERIALS AND METHODS: A total of 70 HCV antibody positive multi
      transfused patients with hemoglobinopathies, who had detectable HCV ribonucleic
      acid, were recruited for genotyping using genotype-specific nested polymerase
      chain reaction. RESULTS: The most frequent genotype detected was genotype 4
      (52.9%) followed by 3a (17.1%), 1b (12.9%) and 1a (1.4%), while mixed genotypes
      (4 with either 3a or 1b) were detected in 7.1%. CONCLUSION: The predominance of
      genotype 4 is similar to other studies from surrounding Eastern Mediterranean
      Arab countries and to the only earlier study from central Iraq, however the
      significant high proportion of 3a and scarcity of 1a, are in contrast to the
      latter study and may be explainable by the differing population interactions in
      this part of Iraq. This study complements previous studies from Eastern
      Mediterranean region and demonstrates relative heterogeneity of HCV genotype
      distribution within Iraq and should trigger further studies in other parts of the
      country.

PMID- 24678172
TI  - Half a decade of mini-pool nucleic acid testing: Cost-effective way for improving
      blood safety in India.
AB  - BACKGROUND AND OBJECTIVES: It is well established that Nucleic acid testing (NAT)
      reduces window phase of transfusion transmissible infections (TTI) and helps
      improve blood safety. NAT testing can be done individually or in pools. The
      objectives of this study were to determine the utility, feasibility and cost
      effectiveness of an in-house minipool-NAT(MP-NAT). MATERIALS AND METHODS: Blood
      donors were screened by history, tested by ELISA and sero-negative samples were
      subjected to an in-house NAT by using reverse transcriptase-polymerase chain
      reaction (RT-PCR). Testing was done in mini-pools of size eight (8). Positive
      pools were repeated with individual samples. RESULTS: During the study period of
      Oct 2005-Sept 2010 (5 years) all blood donors (n=53729) were screened by ELISA.
      Of which 469 (0.87%) were positive for HIV-1, HBV or HCV. Sero-negative samples
      (n=53260) were screened by in-house MP-NAT. HIV-NAT yield was 1/53260 (n=1) and
      HBV NAT yield (n=2) was 1/26630. CONCLUSION: NAT yield was lower than other India
      studies possibly due to the lower sero-reactivity amongst our donors.
      Nevertheless it intercepted 9 lives including the components prepared. The in
      house assay met our objective of improving blood safety at nominal cost and
      showed that it is feasible to set up small molecular biology units in medium
      large sized blood banks and deliver blood within 24-48 hours. The utility of NAT
      (NAT yield) will vary based on the donor population, the type of serological test
      used, the nature of kit employed and the sensitivity of NAT test used. The
      limitations of our in-house MP-NAT consisted of stringent sample preparation
      requirements, with labor and time involved. The benefits of our MP-NAT were that
      it acted as a second level of check for ELISA tests, was relatively inexpensive
      compared to ID-NAT and did not need sophisticated equipment.

PMID- 24678173
TI  - Knowledge, attitude, and beliefs of young, college student blood donors about
      Human immunodeficiency virus.
AB  - INTRODUCTION: Young people, who tend to be healthy, idealistic, and motivated,
      are an excellent pool of potential voluntary unpaid blood donors. Recruiting and
      retaining young blood donors improves the long term safety and sufficiency of a
      country's blood supply. Knowledge, attitude, and beliefs about Human
      immunodeficiency virus (HIV) should play an important role in prevention of
      disease transmission. MATERIALS AND METHODS: This study was a questionnaire based
      survey, conducted to explore the levels of knowledge, attitude, and beliefs about
      HIV in young college student blood donors. RESULTS: The results showed that the
      proportion of participants with comprehensive knowledge of HIV prevention and
      transmission was lesser than expected. Increase in education level and male
      gender was found to be significantly associated with high HIV-related knowledge.
      The responses on the different aspects of HIV-related attitude were also varied
      and there is still stigma associated with Acquired Immunodeficiency Syndrome
      (AIDS) even in the educated groups. DISCUSSION: There was a spectrum of myths and
      misperceptions emphasizing the need of education that recognizes the social
      context of attitude towards HIV. Results from this study may contribute to the
      development of appropriate educational and training material for this group of
      donors which in turn, may assist in achieving the elusive goal of safe blood
      supply in future.

PMID- 24678174
TI  - A single-centre study of vasovagal reaction in blood donors: Influence of age,
      sex, donation status, weight, total blood volume and volume of blood collected.
AB  - CONTEXT: Vasovagal reactions (VVRs) in blood donors. AIM: To find an association
      of age, sex, donation status, weight, total blood volume and volume of blood
      collected with occurrence of immediate VVR. SETTINGS AND DESIGN: Retrospective
      single-centre study. MATERIALS AND METHODS: The study was conducted from March
      2000 to November 2010 at a tertiary care blood transfusion centre. All VVRs with
      or without syncope occurring during or at the end of donation were noted.
      STATISTICAL ANALYSIS USED: For qualitative association, c (2)-test was used.
      Unpaired 't' test was used for assessing difference between two groups with
      respect to VVR status. Simultaneous impact of all risk factors was assessed using
      multivariate logistic regression analysis. The data entry software SPSS (version
      17.0) was used for statistical analysis. A P-value <0.05 was considered
      statistically significant. RESULTS: Overall 1085 VVRs were reported in relation
      to 88,201 donations, resulting in an overall VVR rate of 1.23%, that is, an
      incidence of 1 in every 81 donations. Donors with low blood volume, first-time
      donors, with low weight and female donors had higher absolute donation VVR rates
      than other donors. CONCLUSIONS: Donation-related vasovagal syncopal reactions are
      a multifactorial process determined largely by weight, age, first-time donor
      status and total blood volume. Our study reinforces the fact that blood donation
      is a very safe procedure, which could be made even more event-free by following
      certain friendly, reassuring practices and by ensuring strict pre-donation
      screening procedures.

PMID- 24678175
TI  - The association of transfusion status with antioxidant enzymes and
      malondialdehyde level in Nigerians with sickle cell disease.
AB  - BACKGROUND: Sickle cell disease (SCD) often leads to chronic hemolytic anemia of
      varying severity, and blood transfusion may be employed in the management of SCD
      complications. OBJECTIVE: The aim of the study was to evaluate the effect of
      blood transfusion on the activities of some antioxidant enzymes as well as lipid
      peroxide and to relate transfusion status to these enzymes and malondialdehyde
      (MDA) in SCD patients. MATERIALS AND METHODS: Glutathione peroxidase (GPX),
      superoxide dismutase, catalase, MDA, and lipoproteins were assayed in 87 SCD and
      20 age- and sex-matched subjects with normal hemoglobin. Of the 87 SCD patients,
      30 had multiple transfusions, 21 had been transfused once while 36 had not been
      transfused within the last 3 months. RESULTS: Statistically significant decrease
      in the mean levels of GPX (P = 0.045) and Cu/Zn SOD (P = 0.001) and increased (P
      = 0.001) MDA were observed in the transfused compared to non-transfused patients.
      Similarly, significant decrease (P = 0.001) in Cu/Zn SOD and increase (P = 0.01)
      in MDA were observed in multi transfused compared to those who had been
      transfused once. Transfusion status correlated (P <0.047) inversely with Cu/Zn
      SOD and positively with MDA. CONCLUSION: Reduced activity levels of serum
      antioxidant enzymes and increased mean levels of MDA were observed in transfused
      compared to non-transfused SCD patients and these changes correlated with
      transfusion status.

PMID- 24678176
TI  - Phenotype frequencies of blood group systems (Rh, Kell, Kidd, Duffy, MNS, P,
      Lewis, and Lutheran) in blood donors of south Gujarat, India.
AB  - BACKGROUND: This is the first study on phenotype frequencies of various blood
      group systems in blood donors of south Gujarat, India using conventional tube
      technique. MATERIAL AND METHODS: A total of 115 "O" blood group donors from three
      different blood banks of south Gujarat were typed for D, C, c, E, e, K, Jk(a),
      Le(a), Le(b), P1, M, and N antigens using monoclonal antisera and k, Kp(a),
      Kp(b), Fy(a),Fy(b), Jk(b), S,s, Lu(a), and Lu(b) antigens were typed using
      polyclonal antisera employing Indirect Antiglobulin Test. Antigens and phenotype
      frequencies were expressed as percentages. RESULTS: From the 115 blood donor
      samples used for extended antigen typing in the Rh system, e antigen was found in
      100% donors, followed by D [84.35%], C [81.74%], c [56.32%], and E [21.74%] with
      DCe/DCe (R1 R1, 40.87%) as the most common phenotype. k was found to be positive
      in 100% of donors and no K+k- phenotype was found in Kell system. For Kidd and
      Duffy blood group system, Jk(a+b+) and Fy(a-b-) were the most common phenotypes
      with frequency of 52.17% and 48.69%, respectively. In the MNS system, 39.13%
      donors were typed as M+N+, 37.39% as M+N-, and 23.48% as M-N+. S+s+ was found in
      24.35% of donors, S+s- in 8.69%, and S-s+ as the commonest amongst donors with
      66.96%. No Lu(a+b+) or Lu(a+b-) phenotypes were detected in 115 donors typed for
      Lutheran antigens. A rare Lu(a-b-) phenotype was found in 2.61% donors.
      CONCLUSION: Data base for antigen frequency of various blood group systems in
      local donors help provide antigen negative compatible blood units to patients
      with multiple antibodies in order to formulate in-house red cells for antibody
      detection and identification and for preparing donor registry for rare blood
      groups.

PMID- 24678177
TI  - A case of passenger lymphocyte syndrome following minor ABO incompatible renal
      transplantation.
AB  - Immune hemolysis is one of the adverse effects that can occur following solid
      organ transplantation. Understanding the clinical settings and the various causes
      is necessary for prompt diagnosis and appropriate management. One such condition
      is passenger lymphocyte syndrome (PLS). This case report describes the case of a
      27-year-old male renal allograft recipient of the B-positive blood group who
      received a kidney from an O-positive donor. Postoperatively, the patient showed
      declining hemoglobin (Hb) level and was transfused with B-group packed RBCs
      (PRBCs), following which there was steep fall in Hb level. A request for PRBCs
      was sent to the blood bank and this time cross-match with B-group PRBCs showed
      incompatibility. The patient's RBCs were found to be strongly DAT (direct anti
      globulin test) positive and the eluate showed the presence of anti-B with a titer
      of 32. Thus, diagnosis of probable PLS was made. The patient was managed with
      methylprednisolone, plasmapheresis and O-group PRBCs. Gradually his condition
      improved and was discharged in stable condition. 

PMID- 24678178
TI  - A Rare case of Guillain-Barre syndrome in pregnancy treated with plasma exchange.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune disorder. It is rare in pregnancy
      as there is a decrease in cell-mediated immunity. A case of 28-year-old pregnant
      woman who presented with acute flaccid quadriplegia suffering from GBS is
      discussed in this study. She was treated with plasma exchange in her immediate
      post-partum period. The management of GBS in pregnancy has been discussed. 

PMID- 24678179
TI  - A suspected transfusion transmitted malaria case.

PMID- 24678180
TI  - Investigating weak A subgroups in a healthy lady: The blood bank limitations.

PMID- 24678181
TI  - Testing for hepatitis B virus core antigen and e antigen may confer additional
      safety of donors' blood negative for heptitis B virus surface antigen.

PMID- 24678182
TI  - Seropositive status of dengue virus infection among blood donors in North
      Malaysia.

PMID- 24678183
TI  - Failure of detection of leakage by cell separator during plateletpheresis
      procedures.

PMID- 24678184
TI  - Seropositivity of HIV, Hepatitis B and C, and syphilis among blood donors: A
      retrospective study.

PMID- 24678185
TI  - Barriers to blood donation among non-European migrants in Italy.

PMID- 24678186
TI  - Individual donation nucleic acid technology testing to minimize human
      immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus transfusion
      transmitted infections.

PMID- 24678187
TI  - Anatomy and physiology of peer review process, can it be unbiased?

PMID- 24678188
TI  - Chemoprevention of oral cancer: Green tea experience.
AB  - Oral cancer has a well characterized progression from premalignant oral
      epithelial changes to invasive cancer, making oral squamous cell carcinoma an
      optimal disease for chemoprevention interventions prior to malignant
      transformation. The primary goal of chemoprevention here is to reverse, suppress,
      or inhibit the progression of premalignant lesions to cancer. Due to the extended
      duration of oral pathogenesis, its chemoprevention using natural products has
      been found promising due to their decreased dose and limited toxicity profiles.
      This review discusses with an emphasis on the clinical trials using green tea
      extract (GTE) in chemoprevention of oral premalignant lesions along with use of
      GTE as a chemopreventive agent in various other cancers as well. It is worthwhile
      to include green tea extract in an oral screening program for evaluating the
      premalignant lesions comparing the results between the treated and untreated
      group. Given the wide acceptance of green tea, its benefits may help in effective
      chemoprevention oral cancer. 

PMID- 24678189
TI  - Botulinum toxin: The Midas touch.
AB  - Botulinum Toxin (BT) is a natural molecule produced during growth and autolysis
      of bacterium called Clostridium botulinum. Use of BT for cosmetic purposes has
      gained popularity over past two decades, and recently, other therapeutic uses of
      BT has been extensively studied. BT is considered as a minimally invasive agent
      that can be used in the treatment of various orofacial disorders and improving
      the quality of life in such patients. The objective of this article is to review
      the nature, mechanism of action of BT, and its application in various head and
      neck diseases. 

PMID- 24678190
TI  - Acute respiratory infections among under-5 children in India: A situational
      analysis.
AB  - Acute respiratory infections (ARIs) are the leading cause of death among children
      less than 5 years in India. Emergence of newer pathogenic organisms, reemergence
      of disease previously controlled, wide spread antibiotic resistance, and
      suboptimal immunization coverage even after many innovative efforts are major
      factors responsible for high incidence of ARI. Drastic reduction in the burden of
      ARI by low-cost interventions such as hand washing, breast feeding, availability
      of rapid and feasible array of diagnostics, and introduction of pentavalent
      vaccine under National Immunization Schedule which are ongoing are necessary for
      reduction of ARI. 

PMID- 24678191
TI  - Dentin hypersensitivity following tooth preparation: A clinical study in the
      spectrum of gender.
AB  - OBJECTIVE: The objective of this study was to estimate and compare the incidence
      of dentin hypersensitivity among men and women in an adult population who
      required replacement of missing tooth/teeth with a fixed partial prosthesis
      (FPD). MATERIALS AND METHODS: The study population included 124 subjects (62 men
      and 62 women), who visited the out-patient department in need of FPD for
      replacement of missing teeth. After conducting routine examinations, each
      abutment tooth received two stimuli: Tactile and thermal to assess the
      sensitivity. The measurement of sensitivity was carried out by using a 10 cm
      visual analog scale before preparation and after preparation. The results were
      analyzed statistically using the Mann-Whitney U test. RESULTS: The results showed
      that women reported more dentin hypersensitivity than men before and after tooth
      preparation. CONCLUSION: The results of the present study demonstrated that women
      reported more dentin hypersensitivity than men before and after tooth
      preparation. More studies are needed to explore this nature on gender basis.

PMID- 24678192
TI  - Enhancement of Hippocampal CA3 Neuronal Dendritic Arborization by Glycyrrhiza
      glabra root extract Treatment in Wistar Albino Rats.
AB  - BACKGROUND: In the traditional system of medicine, the roots and rhizomes of
      Glycyrrhiza glabra (Gg) (family: Leguminosae) have been in clinical use for
      centuries. AIM: In the present study, we investigated the role of aqueous extract
      of root of Gg treatment on the dendritic morphology of hippocampal Cornu Ammonis
      area three (CA3) neurons, one of the regions concerned with learning and memory,
      in 1- month- old male Wistar albino rats. MATERIALS AND METHODS: The aqueous
      extract of root of Gg was administered orally in four doses (75, 150, 225 and 300
      mg/kg) for 4 weeks. After the treatment period, all experimental animals were
      subjected to spatial learning (Morris water maze, Hebb-William's maze and
      elevated plus maze) tests. At the end of the spatial memory tests, the rats were
      deeply anesthetized with Pentobarbitone and killed their brains were removed
      rapidly and fixed in rapid Golgi fixative. Hippocampal CA3 neurons were traced
      using camera lucida, and dendritic arborization and intersections were
      quantified. These data were compared to those of age-matched control rats.
      RESULTS: The aqueous root extract of Gg in the dose of 150 and 225 mg/kg/p.o
      showed a significant (P < 0.01) enhancement of dendritic arborization (dendritic
      branching points) and dendritic intersections along the length of both apical and
      basal dendrites in hippocampal (CA3) pyramidal neurons is comparable to control.
      CONCLUSION: Based on our results obtained, we conclude that constituents present
      in aqueous root extract of Gg have neuronal dendritic growth stimulating
      properties.

PMID- 24678193
TI  - Study of extended spectrum beta-lactamase producing Enterobacteriaceae and
      antibiotic coresistance in a tertiary care teaching hospital.
AB  - AIMS: To study the prevalence of extended spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae and coresistance to other commonly used antibiotics
      from the Bhopal region of Central India. SETTINGS AND DESIGN: A prospective study
      was conducted from September 2011 to August 2012 in Microbiology Department of
      our tertiary health care center. MATERIALS AND METHODS: A total of 1044
      Enterobacteriaceae isolates were recovered from various specimens. ESBL
      production was detected by using Clinical Laboratory Standard Institute (CLSI)
      that described the phenotypic confirmatory test along with routine antibiotic
      susceptibility testing. STATISTICAL ANALYSIS: Two-tailed Z-test. RESULTS:
      Escherichia coli was the most common isolate (65.32%). ESBL production was
      confirmed in 504 (48.27%) isolates. The isolates of E. coli (50.14%) were the
      most common ESBL producers. Maximum ESBL isolates were obtained from urine
      samples (52.28%) and male patients (52.54%). Sensitivity to imipenem was 100%
      followed by piperacillin-tazobactam (89.28%), meropenem (87.5%), and amikacin
      (83.92%). Significant resistance was detected against trimethoprim
      sulfomethoxazole, fluoroquinolones, and gentamicin. CONCLUSION: This is the only
      study conducted from Central India and shows high prevalence of ESBL production
      among Enterobacteriaceae. Imipenem seems to be more sensitive than meropenem.
      Piperacillin-tazobactam combination was found to be the best among the beta
      lactam-beta-lactamase inhibitor combinations. Prevalence of ESBL producers were
      more in males than females.

PMID- 24678194
TI  - Elucidating the specificity of non-heparin-based conformational activators of
      antithrombin for factor Xa inhibition.
AB  - INTRODUCTION: Antithrombin, the principal inhibitor of coagulation proteases,
      requires allosteric activation by its physiological cofactor, heparin or heparin
      sulfate to achieve physiologically permissible rates. This forms the basis of
      heparin's use as a clinical anticoagulant. However, heparin therapy is beset with
      severe complications, giving rise to the need to search new non-heparin
      activators of antithrombin, devoid of these complications and with favorable
      safety profiles. MATERIALS AND METHODS: We chose some representative organic
      compounds that have been shown to be involved in coagulation modulation by
      affecting antithrombin and applied a blind docking protocol to find the binding
      energy and interactions of the modified (sulfated) versus unmodified organic
      scaffolds. RESULTS AND CONCLUSION: Increased sulfation plays a key role in
      shifting the specificity of organic compounds like quercetin, diosmin, rutin,
      mangiferin, isomangostin, Trapezifolixanthone and benzofuran towards the heparin
      binding site (HBS). However, in hesperetin and tetrahydroisoquinoline, sulfation
      shifts the specificity away from HBS. We have further tried to elucidate changes
      in the binding affinity of quercetin on account of gradual increase in the number
      of hydroxyl groups being substituted by sulfate groups. The results show gradual
      increase in binding energy with increase in sulfation. A theoretical screening
      approach is an ideal mechanism to predict lead molecules as activators of
      antithrombin and in determining the specificity for antithrombin.

PMID- 24678195
TI  - Enamel hypoplasia of primary canine: Its prevalence and degree of expression.
AB  - BACKGROUND: Enamel hypoplasia is a unique lesion showing wide variations in
      prevalence among populations. The present study aimed to evaluate frequency and
      degree of expression of enamel hypoplasia of primary canine in populations living
      in the eastern part of India. MATERIALS AND METHODS: A prospective cross
      sectional study was performed in randomly selected 3539 school children. Labial
      surfaces of all primary canines were examined. The frequency and degree of
      expression of enamel hypoplasia between different ethnic groups were recorded.
      Based on the location of the defect on the tooth surfaces, the lesions were
      divided as prenatal, perinatal, and postnatal according to stage of
      mineralization. Statistical analysis was carried out using Chi square test.
      RESULTS: The overall prevalence of primary canine hypoplasia was 10.3%. The
      mandibular primary canines were significantly (P = 0.03) more frequently affected
      than maxillary canines among different ethnic groups. The side difference among
      populations was not significant (P = 0.96) statistically. In 8.5% Bengali
      population, 7% Rajbangsi population, and 9.4% in other group of population, the
      defect occurred prenatally. Most of the defects, 64.7% in Bengali, 66.1% in
      Rajbangsi, and 58.8% in others occurred during perinatal stage of mineralization.
      The defect occurred postnatally in 26.8%, 26.7%, and 31.8% in Bengali, Rajbangsi,
      and in other group of population respectively. CONCLUSION: The overall prevalence
      of primary canine hypoplasia was 10.3%. The mandibular primary canines were more
      frequently affected (P = 0.03) than their maxillary counterparts among
      populations. Most of the defects correspond to perinatal stage of mineralization.

PMID- 24678196
TI  - An assessment of etiological spectrum and injury characteristics among
      maxillofacial trauma patients of Government dental college and Research
      Institute, Bangalore.
AB  - BACKGROUND: Maxillofacial injuries pose a therapeutic challenge to trauma,
      maxillofacial and plastic surgeons practicing in developing countries. This was a
      retrospective study carried out to determine the incidence, etiology, injury
      characteristics of maxillofacial injuries reported at our centre. PATIENTS AND
      METHODS: The data for this study were obtained from the medical records of 689
      cases reported to our centre during the period from 2006-2009. Records of
      patients who were either treated in the emergency room as outpatients or the
      Department of Oral and Maxillofacial Surgery as inpatients were analyzed and were
      subjected to statistical analysis using statistical package for social sciences
      (SPSS) for Windows version 17.0. Data was summarized in form of proportions and
      frequency tables for categorical variables and was subjected to Chi-Square test.
      RESULTS: Out of 689 patients, 75.9% were male and 24.1% were female. 42.5% of the
      patients were in the age group of 21 to 30 years. Road traffic accidents
      accounted for the majority (74.3%) of cases of maxillofacial trauma. Mandible was
      seen as the most commonly fractured bone (50.3%) and 53.8% head and neck injuries
      were most common among the associated injuries. CONCLUSION: Road traffic
      accidents were clearly the most prevalent etiological factor for maxillofacial
      trauma. Measures on prevention of road traffic crashes should be strongly
      emphasized in order to reduce the occurrence of these injuries.

PMID- 24678197
TI  - Palatoscopy: An adjunct to forensic odontology: A comparative study among five
      different populations of India.
AB  - OBJECTIVES: This study was conducted to analyze and identify differences in the
      palatal rugae patterns and to identify gender wise changes in the palatal rugae
      shapes in populations of five different states of India. STUDY DESIGN: Study was
      conducted in five different Indian states. 500 sample subjects from Andhra
      Pradesh, Tamil Nadu, Karnataka, Madhya Pradesh and Maharashtra were included.
      Rugae patterns with predominant shapes were analyzed and categorized according to
      different states and both genders, data was statistically analyzed using SPSS
      software 15.0 and the results were obtained by Chi-square analysis. RESULTS:
      "Wavy" type of palatal rugae pattern is the most predominant variant in five
      different study groups in both the genders. CONCLUSION: This study could identify
      variations in distribution of various palatal rugae pattern in five different
      states and confirmed the "wavy" type of palatal rugae patterns to be the most
      predominant variant in five different study groups.

PMID- 24678198
TI  - Frequency distribution of Hepatitis C virus in different geographical regions of
      Punjab: Retrospective study from a tertiary care centre in North India.
AB  - BACKGROUND AND AIM: There is a scarcity of published information on epidemiology
      of Hepatitis C infection in India particularly in Punjab. We conducted a
      retrospective study to assess the frequency distribution, including demographic
      and geographical data of patients with Hepatitis C in different regions of
      Punjab. MATERIALS AND METHODS: We retrospectively collected the clinical,
      demographic and geographical data of 516 patients with Hepatitis C admitted in
      our hospital from January 2010 to December 2010. Punjabi patients with positive
      anti-Hepatitis C virus (HCV)-enzyme linked immune sorbent assay test for the
      detection of anti-HCV antibodies were included. RESULTS: There was predominantly
      rural distribution (67.3%) of patients with maximum cases from Ludhiana district
      (30.04%). Highest frequency of Hepatitis C infection was found in the middle aged
      (41-60 years) patients with male predominance. High proportions (44.8%) of the
      patients included in our study were incidentally detected with Hepatitis C
      infection on routine screening. Various associations of HCV infection with other
      diseases were also identified. CONCLUSIONS: Hepatitis C is an emerging disease in
      Punjab with a sizeable cluster of HCV infected asymptomatic persons who can act
      as a pool for its continuous transmission. The study helps us to predict the
      probable risk factors for Hepatitis C infection in Punjab. The need of the hour
      is to increase awareness about HCV among the public and practicing physicians.

PMID- 24678199
TI  - Prevalence of bronchial asthma and its associated factors among school children
      in urban Puducherry, India.
AB  - BACKGROUND: Bronchial asthma is an important public health problem at the global
      level. There is paucity of studies on bronchial asthma among school children in
      Urban India. OBJECTIVE: To assess the prevalence and associated factors of
      bronchial asthma among school children. MATERIALS AND METHODS: A cross-sectional
      study was conducted among 263 children studying in the 8(th), 9(th), and 10(th)
      standard using the modified International Study on Allergy and Asthma in
      Childhood questionnaire in Urban Puducherry. Data on associated factors that
      include family history of asthma, type of fuel used for cooking, placement of
      kitchen in the house, number of windows in sleeping room, pet animals, smoking
      among family members, birth order, and smoke outlet were collected. Data were
      analyzed by univariate analysis and expressed in proportion or percentages.
      RESULTS: Prevalence of ever bronchial asthma was found to be 5.3%, of which 4.2%
      had current episode of asthma during the last 1-year period. About 72.7% of the
      current asthmatics had cold or rhinitis and 54.5% each had itching or rashes and
      nocturnal dry cough. Prevalence is more among the 12-13 years age group (6.5%)
      compared to the 14-16 years age group (3.6%). Boys (5.4%) and girls (5.2%) had
      comparable prevalence rates. The prevalence was significantly more among those
      with a family history of asthma, having smoking habits in any of the family
      members, and the absence of smoke outlet in the house (P < 0.05). CONCLUSION:
      Bronchial asthma is an important health problem among children in urban
      Puducherry. Intervention on exposure to passive smoking and provision of smoke
      outlets may help to reduce the burden of disease at the community level.

PMID- 24678200
TI  - Study of cognitive functions in newly diagnosed cases of subclinical and clinical
      hypothyroidism.
AB  - INTRODUCTION: Hypothyroidism is associated with significant neurocognitive
      deficits because hypothyroidism prevents the brain from adequately sustaining the
      energy consuming processes needed for neurotransmission, memory, and other higher
      brain functions. Hence, the study was done to assess the cognitive functions of
      newly diagnosed subclinical and clinical hypothyroid patients by evoked response
      potential P300. MATERIALS AND METHODS: 75 patients each of newly diagnosed
      subclinical and clinical hypothyroid patients attending endocrinology clinic and
      75 healthy age and sex matched euthyroid controls were considered for the study.
      P300 was recorded with Record Medicare System Polyrite, Chandigarh using auditory
      "oddball paradigm". The data was analyzed using ANOVA followed by post Tukey's
      test. RESULTS: Newly diagnosed clinical hypothyroid patients showed a significant
      increase in P300 latency compared to control (P < 0.05) and subclinical cases (P
      < 0.01) while there was no significant difference between the P300 latency of
      subclinical cases and control group. Also, there was no significant difference in
      P300 amplitude among the three groups. CONCLUSION: P300 latency in case of newly
      diagnosed hypothyroid clinical cases is significantly increased compared to newly
      diagnosed subclinical cases and control.

PMID- 24678201
TI  - Correlation of oral hygiene practices, smoking and oral health conditions with
      self perceived halitosis amongst undergraduate dental students.
AB  - OBJECTIVE: The present study was undertaken to determine the prevalence of oral
      hygiene practices, smoking habits and halitosis among undergraduate dental
      students and correlating the oral hygiene practices, oral health conditions to
      the prevalence of self perceived oral malodour. MATERIALS AND METHODS: A self
      administered questionnaire was distributed among 277 male and female students. A
      questionnaire was developed to assess the self-reported perception of oral
      breath, awareness of bad breath, timing of bad breath, oral hygiene practices,
      caries and bleeding gums, dryness of the mouth, smoking and tongue coating.
      RESULTS: The results indicate female students had better oral hygiene practices.
      Significantly less self-reported oral bad breath (P = 0.007) was found in female
      dental students (40%) as compared to their male counterparts (58%). It was found
      that smoking and dryness of mouth had statistically significant correlation with
      halitosis (P = 0.026, P = 0.001). Presence of other oral conditions such as
      tongue coating and dental caries and bleeding gums also showed higher prevalence
      of halitosis in dental students. CONCLUSION: A direct correlation exists between
      oral hygiene practices and oral health conditions with halitosis. Females
      exhibited better oral hygiene practices and less prevalence of halitosis as
      compared to male students.

PMID- 24678203
TI  - Immediate implants in anterior maxillary arch.
AB  - AIM: The aim of the study was to evaluate the osseo-integration and soft tissue
      status of the endosseous implants placed in immediate extraction socket.
      METHODOLOGY: Seven patients (4 males and 3 females) aged 20-30 years were
      selected for the study. Nine implants were placed in seven patients in the
      maxillary arch. All the patients were clinically alphand thoroughly examined.
      Under local anesthesia, the indicated tooth was extracted. The extracted socket
      was prepared using standard drills with palatal wall as guide. The longest and
      widest implants were placed (Hi-Tec Implants). All implants showed good primary
      stability. The implants used in the study were tapered design endosseous implants
      with Threaded implants (TI) unit plasma-sprayed surface. Surgical re-entry
      (secondary surgery) was performed to remove the healing cap after 6 months for
      supra crestal fabrication. All patients were reviewed periodically at 3(rd) and
      6(th) month interval and the following clinical parameters including modified
      plaque index (mPlI), modified bleeding index (mBI), probing depth (PD),
      attachment level (AL), and distance between the implant shoulder and mucosal
      margin (DIM), distance between the implant shoulder and first bone-implant
      contact, and Clinical Mobility Index were recorded. The results were computed and
      subjected to statistical evaluation. RESULTS: The mPlI, mBI, PD, AL, and DIM were
      evaluated around the implants at baseline, 3(rd) and 6(th) month intervals and
      analyzed statistically by Friedman T-test. The results of the above were shown to
      be statistically non-significant. The distance between the implant shoulder and
      first bone implant contact was evaluated around the implants at base line, 3(rd)
      and 6(th) month intervals. The results proved to be statistically significant
      (0.01) implying that there was a bone apposition around the implants. CONCLUSION:
      During the course of the study, soft tissue status around implants was found to
      be healthy. Osseointegration as assessed by clinical and radiographic findings
      was found to be sound.

PMID- 24678202
TI  - Insights from computational analysis of full-length beta-ketoacyl-[ACP] synthase
      II cDNA isolated from American and African oil palms.
AB  - BACKGROUND: Palm oil derived from fruits (mesocarp) of African oil palm (Elaeis
      guineensis Jacq. Tenera) and American oil palm (E. oleifera) is important for
      food industry. Due to high yield, Elaeis guineensis (Tenera) is cultivated on
      commercial scale, though its oil contains high (~54%) level of saturated fatty
      acids. The rate-limiting activity of beta-ketoacyl-[ACP] synthase-II (KAS-II) is
      considered mainly responsible for the high (44%) level of palmitic acid (C16:0)
      in the oil obtained from E. guineensis. OBJECTIVE: The objective of this study
      was to annotate KAS-II cDNA isolated from American and African oil palms.
      MATERIALS AND METHODS: The full-length E. oleifera KAS-II (EoKAS-II) cDNA clone
      was isolated using random method of gene isolation. Whereas, the E. guineensis
      KAS-II (EgTKAS-II) cDNA was isolated using reverse transcriptase polymerase chain
      reaction (RT-PCR) technique; and missing ends were obtained by employing 5'and 3'
      RACE technique. RESULTS: The results show that EoKAS-II and EgTKAS-II open
      reading frames (ORFs) are of 1689 and 1721 bp in length, respectively. Further
      analysis of the both EoKAS-II and EgTKAS-II predicted protein illustrates that
      they contains conserved domains for 'KAS-I and II', 'elongating' condensing
      enzymes, 'condensing enzymes super-family', and '3-oxoacyl-[ACP] synthase II'.
      The predicted protein sequences shows 95% similarity with each other.
      Consecutively, the three active sites (Cys, His, and His) were identified in both
      proteins. However, difference in positions of two active Histidine (His) residues
      was noticed. CONCLUSION: These insights may serve as the foundation in
      understanding the variable activity of KAS-II in American and African oil palms;
      and cDNA clones could be useful in the genetic engineering of oil palms.

PMID- 24678205
TI  - Clinico-immunological profile and their correlation with severity of atopic
      dermatitis in Eastern Indian children.
AB  - OBJECTIVE: To study the clinical features, absolute eosinophil count, and total
      immunoglobulin E (IgE) level and their association with severity of atopic
      dermatitis in Eastern Indian children (Bihar). DESIGN: Prospective hospital-based
      study. SETTINGS: Pediatrics out-patient Department (OPD) and Dermatology OPD of a
      Tertiary Care Teaching Hospital located in Rohtas District of Bihar. The study
      was carried out over a period of 2 years during January 2010 to December 2011.
      PARTICIPANTS: One hundred and thirty two children aged 0 month to 15 years were
      diagnosed with atopic dermatitis. MAIN OUTCOME: Demographic profile, common
      clinical features, absolute eosinophil count, and total IgE level and their
      correlation with severity of atopic dermatitis in Eastern Indian children.
      RESULTS: Out of a total 1829 pediatric patients aged 0 month to 15 years with
      some pediatric dermatoses, 132 (7.21%) had atopic dermatitis. Of 132 patients, 57
      (43.2%) were boys and 75 (56.8%) were girls, with a male to female ratio 1:1.3.
      Of these 29 were infants and 103 were children. Two (62.1%) patients belonged to
      rural area whereas 50 (37.9%) belonged to urban area. Personal history, family
      history (up to third degree relatives), and both personal and family history of
      atopy were present in 43.18%, 33.34%, and 12.1% of the subjects respectively.
      Majority (89.4%) of patients had onset before 5 years of age. In infantile Atopic
      dermatitis (AD), mean age +/- SD at onset was 5.2 months +/- 3.01 months. In
      infantile group, 8 (27.6%) had mild, 14 (48.3%) moderate, and 7 (24.1%) had
      severe atopic dermatitis. Infantile AD had statistically significant higher
      SCORing Atopic Dermatitis (SCORAD) index score in all three grades of severity of
      the disease. One hundred and three patients had childhood AD, out of which 40
      (38.8%) were boys and 63 (61.2%) were girls, with a male to female ratio 1:1.57.
      In childhood AD, mean age +/- SD at onset of the disease was 3.47 years +/- 3.02
      years. Sixty three (61.1%) belonged to rural area whereas 40 (38.9%) were from
      urban area. One hundred and thirty (98%) patients presented with itching. Ninety
      two (69.7%) patients had high absolute eosinophils count (AEC) with mean +/- SD
      of 1004.1 +/- 596.2 (range 325-2510). Eighty seven (65.9%) patients had increased
      total serum immunoglobulin E (TsIgE) with mean +/- SD value of 1127.11 IU/ml +/-
      731.69 IU/ml (range: 125-2680 IU/ml). CONCLUSION: Epidemiological data on atopic
      dermatitis in India are mainly hospital-based, true-point prevalence in community
      is still scanty. Although the prevalence of AD is considered to be increasing, it
      still remains low in comparison to developed countries. In Indian children, the
      disease is relatively milder than children of developed countries. This study
      identified that both AEC and TsIgE increased significantly in about 66% patient
      and directly correlated with the severity of the AD.

PMID- 24678204
TI  - Estimation of serum and salivary immunoglobulin G and immunoglobulin A in oral
      pre-cancer: A study in oral submucous fibrosis and oral lichen planus.
AB  - AIM: Oral submucous fibrosis (OSMF) and oral lichen planus (OLP) are two
      frequently reported, potentially malignant disorders with multifactorial
      etiologies and ambiguous pathogenesis. An immunological pathogenesis has been
      hypothesized as a causative factor for both. The present study aims to evaluate
      the role of serum and salivary immunoglobulin G (IgG) and immunoglobulin A (IgA)
      in both these conditions, by their quantitative estimation. MATERIALS AND
      METHODS: Saliva and serum samples were collected from 30 patients, clinically
      diagnosed and histopathologically confirmed with OSMF, 30 with OLP and 30 age and
      sex matched controls. The levels of IgG and IgA were estimated by nephelometry.
      RESULTS: The mean values of serum IgG were marginally higher in both OSMF and OLP
      groups compared to the controls but this difference was not significant and the
      mean values of serum immunoglobulin A were marginally decreased in both the study
      groups compared to the controls but this difference was also not significant.
      Inconclusively low levels of salivary IgG and IgA were obtained in the three
      groups. CONCLUSION: The present study suggests an insignificant association of
      these immunoglobulins in the pathogenesis of both these diseases.

PMID- 24678206
TI  - Correlation of oral health status of socially handicapped children with their
      oral heath knowledge, attitude, and practices from India.
AB  - BACKGROUND: Information on oral health knowledge and practice in orphanage house
      children is essential for healthcare policy makers to promote oral health
      resources and address oral health needs of this unprivileged group of society.
      OBJECTIVES: To assess the source of information, level of knowledge, attitude,
      and practice toward oral hygiene and oral health among socially handicapped
      children from city of Mysore, Karnataka state, India. MATERIALS AND METHODS: A
      cross-sectional survey was conducted among 488 children of 12-14 years of age
      living in five different orphanage houses of Mysore district. Data regarding
      knowledge and practice were collected through structured questionnaire and oral
      health status by type III clinical oral examinations by two trained examiners.
      Decayed, Missing, Filled, Teeth (DMFT) and OH I-S was then correlated with the
      above information. Spearman's correlation test was used to measure the
      correlation. RESULTS: The final data analysis included 488 children, of which 216
      (44.26%) were boys and 272 (55.74%) were girls. A total of 88.5% children showed
      one or more decayed teeth in their oral cavity, with an overall mean DMFT of
      3.55. Among DMF, component D showed maximum value with mean 3.42, followed by
      components F and M. Correlation between source of information, knowledge, and
      attitude for oral health to oral hygiene index (OHI-S; P < 0.05) and gingival
      index (P < 0.001) showed highly significant negative values. Correlation between
      oral hygiene practice to OHI-S, DMFT, and gingival index (P < 0.001) showed
      highly significant (P < 0.001) negative values. CONCLUSIONS: Although children of
      orphanage have positive attitude toward oral health, knowledge and practice among
      children are still below the satisfactory level. The children did not receive
      appropriate information or, if informed, were not re-evaluated or reinforced for
      its practical application by the concerned authority. The findings of this study
      suggest that awareness on the importance of oral health needs to be enhanced
      among the orphanage children of Mysore.

PMID- 24678207
TI  - Docking studies for screening anticancer compounds of Azadirachta indica using
      Saccharomyces cerevisiae as model system.
AB  - INTRODUCTION: Plants have a long history of use in the treatment of cancer. Plant
      derived compounds have played an important role in the development of several
      clinically useful anticancer agents. In the recent years, more emphasis has been
      placed on identifying plant-derived compounds that can be used as an effective
      treatment for life-threatening diseases such as cancer. Cancer is a disease where
      there is abnormal cell proliferation. The proliferation of the cancer cells are
      restrained by cdk/cyclin complexes, which control the normal process of cell
      cycle. MATERIALS AND METHOD: The current study involves the investigation of the
      anticancer property of the chemical compounds present in the leaves of
      Azadirachta indica by performing docking studies with the cell cycle control
      protein using Arguslab. RESULT: The compounds were docked with the cdk1 protein
      to identify suitable inhibitors against the protein function. CONCLUSION: The
      study were conducted on yeast Cdk protein, because these proteins showed homology
      with the human Cdks.

PMID- 24678208
TI  - Immunohistochemical analysis of factors related to apoptosis and cellular
      proliferation in relation to inflammation in dentigerous and odontogenic
      keratocyst.
AB  - BACKGROUND: The effect of inflammation on pathogenesis and biological behavior of
      odontogenic keratocyst (OKC) and dentigerous cyst (DC) is not completely
      understood. Hence, we aimed to analyze the effect of inflammation on biological
      behavior of OKC and DC using a proliferative and anti-apoptotic marker, i.e.,
      proliferative cellular nuclear antigen (PCNA) and Bcl-2, respectively. MATERIALS
      AND METHODS: Immunohistochemical staining was performed using anti-PCNA and Bcl-2
      antibody in 10 cases each of classical OKC, inflamed OKC and classical DC and
      inflamed DC. RESULTS: Inflamed OKC and DC showed a significant increase in PCNA
      expression and decrease in Bcl-2 expression when compared with non-inflamed cyst.
      Correlation between inflammation and proliferative and anti-apoptotic activity
      was found to be statistically non-significant. CONCLUSION: Inflammation is
      responsible for change in behavior of neoplastic epithelium of OKC and hence
      should be treated meticulously, whereas in DC it is responsible for changes in
      the epithelial lining.

PMID- 24678209
TI  - Decadorial of a burn center in Central India.
AB  - INTRODUCTION: Burn injuries are a serious public health problem. In our study we
      have identified different epidemiological factors based on 10 years of our
      experience at a burn unit in central India and recommend some strategies to
      prevent burn injuries. MATERIALS AND METHODS: This is a retrospective analysis
      (2001-2010) of database from burn unit of S.S. Medical College, Rewa, India.
      RESULTS: 2499 patients with burn injury were analysed. 66.8% and 38.2% patients
      were females and males respectively, with a median age of 25 years. Flame (80.1%)
      was most common cause, home (96%) was most common place, traditional Indian stove
      (28.8%), kerosene lamp (26.7%), hot liquid (12.2%) and kerosene stove (10.4%)
      were common causes. Median Total Body Surface Area (TBSA) burn was 40.0%; females
      had significantly greater (P < 0.001) burn than males (median 50% vs 26.0%). High
      mortality (40.3%) seen; female sex (OR 3.22, 95% CI 2.65-3.92); young age (15-29
      year) (OR 3.48, 95% CI 2.45-4.94); flame burn (OR 12.9, 95% CI 1.69-98.32);
      suicidal burn OR 6.82 95%CI 4.44-10.48) and TBSA > 76% (OR 3099, 95%CI 1302-7380)
      were significant risk factors for death. Median hospital stays was 8 days;
      shorter hospital stays seen among TBSA burn > 76% (2 days), suicidal intent (4
      days), and those who expired (4 days). Septicemia (45.8%) and burn shock (41%)
      were the major cause for death. CONCLUSIONS: Cooking and lighting equipments are
      major cause of burn injury among females and young age group. Equipment
      modification to improve safety features and public awareness programs are
      necessary to reduce burn incidents.

PMID- 24678210
TI  - Effect of moisture, saliva, and blood contamination on the shear bond strength of
      brackets bonded with a conventional bonding system and self-etched bonding
      system.
AB  - BACKGROUND: The success of bonding brackets to enamel with resin bonding systems
      is negatively affected by contamination with oral fluids such as blood and
      saliva. The new self-etch primer systems combine conditioning and priming agents
      into a single application, making the procedure more cost effective. OBJECTIVE:
      The purpose of the study was to investigate the effect of moisture, saliva and
      blood contamination on shear bond strength of orthodontic brackets bonded with
      conventional bonding system and self-etch bonding system. MATERIALS AND METHODS:
      Each system was examined under four enamel surface conditions (dry, water,
      saliva, and blood), and 80 human teeth were divided into two groups with four
      subgroups each of 10 according to enamel surface condition. Group 1 used
      conventional bonding system and Group 2 used self-etched bonding system.
      Subgroups 1a and 2a under dry enamel surface conditions; Subgroups 1b and 2b
      under moist enamel surface condition; Subgroups 3a and 3b under saliva enamel
      surface condition and Subgroup 4a and 4b under blood enamel surface condition.
      Brackets were bonded, and all the samples were then submitted to a shear bond
      test with a universal testing machine with a cross head speed of 1mm/sec.
      RESULTS: The results showed that the contamination reduced the shear bond
      strength of all groups. In self-etch bonding system water and saliva had
      significantly higher bond strength when compared to other groups. CONCLUSION: It
      was concluded that the blood contamination showed lowest bond strength from both
      bonding systems. Self-etch bonding system resulted in higher bond strength than
      conventional bonding system under all conditions except the dry enamel surface.

PMID- 24678211
TI  - Serum zinc levels and its association with vitamin A levels among tuberculosis
      patients.
AB  - INTRODUCTION: One-third of the total human population is infected with the
      Mycobacterium tuberculosis. This bacterium causes illness in up to 9 million
      people annually and is responsible for three deaths every minute world-wide.
      OBJECTIVE: To determine the association of serum zinc level with vitamin A level
      in active pulmonary tuberculosis (TB) cases. MATERIALS AND METHODS: It was a
      cross-sectional study of 208 active pulmonary TB patients aged 18-55 years. Blood
      samples were obtained from these patients to determine the serum zinc and serum
      retinol levels. RESULTS: The mean age of the patients was 30.56 (+/-11.38) years
      ranging from 18 years to 55 years. More than half (54.3%) of the patients were
      males and 63% were married. Body mass index of the patients was 18.40 +/- 3.10.
      The serum zinc and vitamin A levels among the patients were 9.60 (+/-0.86)
      MUmol/l and 0.77 (+/-0.22) MUmol/l respectively. However, haemoglobin, white
      blood cell, erythrocyte sedimentation rate, and serum albumin were 10.02 (+/
      1.33) g/dl, 10076.01 (+/-1822.67) cell/mm3, 14.50 (+/-2.95) mm/h and 3.40 (+/
      0.32) g/dl respectively. There was a strong correlation between serum zinc and
      vitamin A levels (r = 0.86, P < 0.01). Vitamin A levels were not significantly
      different among the different age groups; however, this was significantly (P =
      0.001) higher in male (0.82 +/- 0.23, 95% confidence interval [CI] =0.77-0.86)
      patients as compared to females (0.71 +/- 0.20, 95% CI = 0.67-0.75). CONCLUSION:
      Zinc deficiency may indirectly influence the metabolism of Vitamin A via
      reduction of the levels of circulating proteins.

PMID- 24678212
TI  - Out of pocket expenditure among the households of a rural area in Puducherry,
      South India.
AB  - BACKGROUND: As a measure to reduce the out of pocket health spending in our
      country, the high level expert group on Universal Health Coverage recommends a
      National Health Package free of cost to all. Whether availability of services
      free of cost, will reduce out of pocket expenditure? AIM: To assess this, we
      studied the out of pocket health spending among the households of a
      Ramanathpuram, a village in Puducherry, where surplus health services are
      available free of cost. SETTINGS AND DESIGN: An exploratory study was conducted
      in by 200 purposively selected households of Ramanathpuram, during the months of
      March-April 2012. MATERIALS AND METHODS: Information was sought on socio
      demographic details (age, gender, and income), expenditure incurred during OPD
      visits, follow up for chronic diseases, and hospitalization using a pretested
      questionnaire. Recall periods of 1 and 3 months were considered for OPD visits
      and hospitalizations, respectively. RESULTS: Of the total 935 individuals from
      the 200 households included, 51.3% (480) were men and 455 (48.7%) were women. A
      total of 231 visits to health care facilities were recorded from 143 (71.5%)
      households, of which 153 (66.2%) were for acute illness and 68 (29.4%) for follow
      up of chronic diseases and 10 (4.3%) for hospitalization. The mean per visit
      expenditure for acute illness, chronic diseases, and hospitalization were INR72.7
      +/- 143.6, 135.7 +/- 196.2, and 1340 +/- 1192.9, respectively. Government
      facilities were availed for 175 (75.7%) visits. Majority of those who incurred
      health expenditure for acute illness (80.4%) and utilized the private sector for
      acute illness (78.4%) were from higher socioeconomic class (P = 0.001).
      CONCLUSION: Majority (58.1%) of the households did not incur health care
      expenditure. Public health care facilities were preferred (75.5%) for seeking
      care. Availability of services free of cost reduces out of pocket expenditure
      among non-hospitalized cases.

PMID- 24678213
TI  - Anomalies in primary dentition: Their distribution and correlation with permanent
      dentition.
AB  - BACKGROUND: Anomalies in primary dentition are often found to be associated with
      anomalies in permanent dentition. AIMS: This study was performed to evaluate the
      prevalence of supernumerary teeth, hypodontia, double teeth, and talon cusp in
      the primary dentition, and their effect on succedaneous permanent teeth.
      MATERIALS AND METHODS: In this prospective cross-sectional study, we clinically
      investigated 2757 Bengali speaking nursery children (1474 girls and 1283 boys),
      of age four to six years, at their respective schools, and the presence of
      supernumerary teeth, hypodontia, double teeth, and talon cusp in the primary
      dentition were recorded. Children with anomalous primary teeth were further
      subjected to periapical and panoramic radiographic examination, to determine the
      status of the underlying permanent teeth. RESULTS: The total prevalence of all
      anomalies in this study was 1.8%. A total of 38 children (21 girls and 17 boys)
      had anomalies. The prevalence of anomalies was as follows: Supernumerary teeth
      (0.4%), hypodontia (0.5%), double teeth (0.4%), and talon cusp (0.07%), in both
      sexes combined. Radiographic examination showed 50% of the patients (19 children)
      had anomalies in the permanent dentition. CONCLUSIONS: Anomalies in primary
      dentition exhibited a correlation with anomalies in permanent dentition.

PMID- 24678214
TI  - Utilization of maternal health-care services by tribal women in Kerala.
AB  - BACKGROUND: The coverage of maternal care services among the tribal women in
      Kerala is better as compared to other states in India. AIM: This study was done
      to identify the factors contributing to better coverage of maternal care services
      among the tribal women in Kerala and to study the reasons for remaining
      differences that exists in utilization of services between tribal and non-tribal
      pregnant women. SETTINGS AND DESIGN: This was a descriptive cum qualitative study
      conducted in Thariode Gramapanchayat in the Wayanad district of Kerala. MATERIALS
      AND METHODS: Among all women who had registered their pregnancies in the 5 sub
      centres under CHC Thariode and had delivered between September 2009 and October
      2010, equal numbers of tribal and non-tribal ante-natal women, 35 each were
      interviewed in-depth using a semi-structured questionnaire. STATISTICAL ANALYSIS
      USED: Quantitative data was analysed using SPSS Version 16.0. Content analysis
      was done for qualitative data. RESULTS: The determinants of utilization in tribal
      women were general awareness, affordability, accessibility and quality of
      services along with motivation by health workers. Among tribal antenatal women,
      85% utilized maternal health care facilities fully compared to 100% among non
      tribal women. Lower levels of education and lack of transport facilities were
      prime factors contributing to under utilization by tribal women. CONCLUSIONS:
      Affordable, accessible and good quality of services in the public health system
      in Kerala and motivation by health workers were important contributing factors
      for better utilization of maternal care services.

PMID- 24678215
TI  - Detection of species diversity in oral candida colonization and anti-fungal
      susceptibility among non-oral habit adult diabetic patients.
AB  - BACKGROUND AND OBJECTIVES: Patients with diabetes mellitus are prone to secondary
      infections. In this study we aim to determine the prevalence of one such
      secondary infection (oral Candida colonization) and evaluate the influence of
      local and systemic factors on the oral candidal colonization in patients with
      diabetes mellitus. MATERIALS AND METHODS: Forty non-insulin-dependent diabetic
      patients and 40 healthy individuals were included in this study. Samples were
      collected by using the oral rinse method. The candidal species were isolated and
      identified through phenotypic methods. An in vitro antifungal susceptibility
      profile was evaluated. Glycemic control, as determined by the glycosylated
      hemoglobin concentrations (HbA1c) of the study subjects, was correlated with the
      candidal colonization. RESULTS: Patients with diabetes showed a significantly
      higher prevalence of candidal colonization. The rate of carriage and density (P =
      0.001) was higher. Candida albicans was the most predominantly isolated species,
      however, C. dubliniensis, C. tropicalis, and C. parapsilosis were also observed.
      Variable resistance toward the antifungal drugs (amphotericin B and fluconazole)
      was observed in the Candida isolated from diabetics, but not from healthy
      patients. Interestingly, a positive correlation was observed between glycemic
      control and candidal colonization. CONCLUSION: Diabetic patients had a higher
      candidal carriage rate, with a variety of candidal strains, which significantly
      varied in their resistance to routinely used anti-fungal agents. Interestingly
      the higher oral candidal colonization in diabetic patients is related to local
      and systemic factors, independent of their oral habits.

PMID- 24678216
TI  - Outcome of forceps delivery in a teaching hospital: A 2 year experience.
AB  - INTRODUCTION: The art of forceps delivery though existing for centuries has
      earned a disreputation due to the possibility of poor maternal and fetal outcome.
      However, its safe use can reduce the rising cesarean section rates in the present
      times. This study is to see the outcome of its use in a teaching hospital over a
      2 year period. MATERIALS AND METHODS: In this retrospective observational study,
      120 cases of forceps delivery were studied for maternal outcome such as injuries,
      postpartum hemorrhage, and fetal outcome such as Apgar score at birth, neonatal
      intensive care unit admissions, injury, and mortality. RESULTS: The most common
      indication was fetal distress (47.5%). A total of 15 cases (12.5%) of maternal
      injuries occurred, with 2 uterine ruptures one of which was in a previous lower
      segment caesarean section case, 4 complete perineal tears and 9 minor cervical
      and vaginal lacerations. A total of 12 babies (10%) had poor Apgar scores who
      recovered after resuscitation and one out of them died, which was a case of
      multiple instrumentation. CONCLUSION: Forceps is a reasonable option for the
      obstetrician to reduce the caesarean section rates; however, extreme caution,
      proper expertise and judicial use of this instrument are required to prevent
      undue risk to mother and fetus.

PMID- 24678217
TI  - Impact of iron deficiency anemia on cell-mediated and humoral immunity in
      children: A case control study.
AB  - OBJECTIVE: The precise role of iron in immune regulation especially in children
      vulnerable to iron deficiency is not fully known. Hence, this study was conducted
      to evaluate the effects of iron deficiency anemia (IDA) and its treatment with
      oral iron supplementation on cell-mediated immunity (CMI) and humoral immunity
      (HMI) in children. MATERIALS AND METHODS: A total of 40 children (<15 years) with
      IDA and 40 age-matched healthy children after satisfying the inclusion criteria
      were enrolled for this case-control study. Flow cytometric evaluation of absolute
      and relative numbers of cluster of differentiation 4 (CD4) and CD8 (cluster of
      differentiation 8) lymphocyte subgroups was carried out to assess the CMI and
      serum Immunoglobulin G (IgG), Immunoglobulin A (IgA), Immunoglobulin M (IgM) were
      measured to assess the HMI at baseline and 3 months post oral iron
      supplementation. RESULTS: Significantly lower levels (P < 0.05) of CD4+ T-cells
      and decreased CD4:CD8 ratios were observed in the iron deficient children. Iron
      supplementation significantly improved the CD4+ cell counts and CD4:CD8 ratios.
      However, immunoglobulin levels weren't different between the two groups.
      CONCLUSIONS: Although IDA did not influence HMI, it significantly impaired CMI,
      which was improved following iron supplementation for 3 months.

PMID- 24678218
TI  - Incidence of nutrient canals in hypertensive patients: A radiographic study.
AB  - OBJECTIVES: To determine if any correlation exists in the presence of nutrient
      canals in hypertensive patients and nonhypertensive patients, to compare the
      incidence of nutrient canals in different age groups, and also to compare the
      incidence of nutrient canals between dentulous and edentulous patients. MATERIALS
      AND METHODS: This study was carried out on patients, who were divided into a
      control group comprising of healthy individuals, without history of hypertension
      and a study group of patients with the history of hypertension. The necessary
      information like age of the patient, presence or absence of hypertension, its
      duration, and blood pressure were recorded. An intraoral periapical radiograph of
      lower anterior region was made using bisecting angle technique and was
      interpreted. The presence or absence of nutrient canals, bone loss, and the
      levels of bone loss were recorded. The results so obtained were subjected to
      statistical analysis. RESULTS: We found that the incidence of nutrient canals was
      statistically higher in the study group (55.2%) as compared to the control group
      (36.2%). The incidence of nutrient canals was also found to be increased with,
      the age till 60 years, amount of alveolar bone loss and in edentulous patients.
      CONCLUSION: Hypertension being one of the most commonly encountered medical
      problems in dental practice and many cases being undiagnosed, the presence of
      nutrient canal though not entirely indicative of hypertension, should increase
      the suspicion of the condition to be investigated further.

PMID- 24678219
TI  - Tuberculous brain abscess in an immunocompetent adolescent.
AB  - Tuberculous brain abscess (TBA) is one of the rare forms of central nervous
      system tuberculosis. A case of tuberculous cerebellar abscess in a young
      immunocompetent adult male is being described. There was no clinical or
      radiological evidence of active tuberculosis elsewhere in the body. The diagnosis
      of tubercular abscess was confirmed by demonstration of acid fast bacilli in the
      abscess material aspirated via a burr hole. High index of suspicion and timely
      intervention is required to diagnose and treat this potential fatal but easily
      treatable condition. 

PMID- 24678220
TI  - Unilateral multiple variations of renal, phrenic, suprarenal, inferior mesenteric
      and gonadal arteries.
AB  - Knowledge of the branching pattern of the abdominal aorta is clinically important
      for any abdominal surgeon operating on parts of the gut or neighboring
      structures. Variations of these vessels may influences urological, renal
      transplantation and laparoscopic surgeries. We present an unreported case of
      multiple variations of branching pattern of abdominal aorta. It includes double
      renal arteries for left kidney, a common trunk with right and left phrenic, right
      and left superior suprarenal and left middle supra renal arteries, and a common
      trunk originate 2.5 cm above the bifurcation of abdominal aorta gave off inferior
      mesenteric, accessory renal artery to the left kidney and left testicular
      arteries in the middle-aged normal male cadaver. The embryogenesis of such
      multiple variations of branches of abdominal aorta is not clear, but the anatomic
      consequences may have important clinical implications. Knowledge of these
      variations is important for urologists, radiologists and surgeons in general. 

PMID- 24678221
TI  - A rare case of Kartagener's syndrome.
AB  - A young boy presented with cough and intermittent breathlessness for 3 months. He
      used to suffer from frequent cough and cold since childhood. Clinical examination
      revealed bilateral coarse basal crepitations and rhonchi. His apex beat was on
      right 5(th) intercostal space in mid-clavicular line. Investigation revealed
      situs inversus, bi-lateral bronchiectasis, and chronic sinusitis. His semen
      analysis revealed the complete absence of sperm. The Saccharin test revealed
      impaired nasal ciliary movement. Considering all the finding, he was diagnosed as
      a case of Kartagener's syndrome. We are reporting this case because of its rarity
      and rare presence of aspermia in Kartagener's syndrome. 

PMID- 24678222
TI  - Management of palato radicular groove in a maxillary lateral incisor.
AB  - This study is to report the rare localization of a radicular groove on the
      palatal aspect of the maxillary lateral incisor and to discuss the pathology and
      management of the concomitant endo-periodontal defect. Unilateral palato
      radicular groove was located on the Maxillary right lateral incisor of an 18-year
      old female patient. The groove was associated with deep local periodontal pocket
      resulting in pulp necrosis and the formation of a large periapical lesion. A
      collaborative management was carried out using a combination of endodontic
      therapy, surgical enucleation, odontoplasty, and periodontal regenerative
      procedure resulting the successful healing of the periapical lesion. 

PMID- 24678223
TI  - Dexmedetomidine induced catecholamine suppression in pheochromocytoma.
AB  - Pheochromocytoma is a neuroendocrine tumour of chromaffin cells, though rare but
      a known cause of paroxysmal hypertension with a triad of headache, diaphoresis
      and palpitation. The biochemical diagnosis of pheochromocytoma is based on
      estimation of plasma nor-adrenaline, adrenaline and their metabolites in plasma
      or urine. Clonidine suppression test is performed to differentiate the raised
      catecholamine level due to pheochromocytoma or other than heochromocytoma
      especially in cases where plasma nor-adrenaline levels are less than 2000 pg/ml.
      Clonidine is stated to be unable to suppress catecholamine level in cases of
      pheochromocytoma, therefore we tested the other alpha2-agonist Dexmedetomidine
      intravenous in a case of Pheochromocytoma with remarkably raised nor- adrenaline
      (25,183 pg/ml) and found 49.42% suppression. 

PMID- 24678224
TI  - Primary tubercular mastitis masquerading as malignancy.
AB  - The significance of primary tubercular mastitis is due to rare occurrence and
      often overlooked and misdiagnosed as pyogenic breast abscess or malignancy.
      Despite the high incidence of tuberculosis in India, reports of breast
      tuberculosis among the total number of mammary conditions varies between 0.64%
      and 3.59%. We report a case of a 35-year-old lady with breast lump of 3 months
      duration, which simulated malignancy on clinical examination but fine needle
      aspiration cytology revealed granulomatous mastitis secondary to tuberculosis.
      High level of suspicion and simple fine needle aspiration procedure with micro
      biological tests will clinch the final diagnosis. 

PMID- 24678225
TI  - Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract.
      Management and literature review.
AB  - Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of
      patients with extremity soft tissue sarcoma and in 4.5% of patients with
      liposarcoma. Multifocal disease may arise either synchronously or metachronously
      and has been associated with poor prognosis. Herein, we have described a rare
      case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal
      tract that developed 14 months after the resection of a myxoid buttock
      liposarcoma. Diagnostic evaluation and management of the patient are discussed
      along with a review of the relevant literature. We conclude that multifocal
      myxoid liposarcoma is a rare clinical entity that usually represents metastatic
      disease with poor prognosis. A thorough imaging and careful physical examination
      are essential in the preoperative evaluation and postoperative follow-up of
      patients with myxoid extremity liposarcomas, as these tumors are known to have a
      tendency to spread toward extrapulmonary sites, frequently without pulmonary
      metastases. 

PMID- 24678226
TI  - Giant cemento-ossifying fibroma of the mandible.
AB  - Cemento-ossifying fibroma (COF) is classified as a fibro-osseous neoplasm and
      included among the non-odontogenic tumors derived from the mesenchymal blast
      cells of the periodontal ligament, with a potential for forming fibrous tissue,
      cementum and bone, or a combination of such elements. These are slow-growing
      lesions, and are more frequent in women between the third and fourth decades of
      life. Case reports of massive expansile COF, measuring more than 10 cm are rarely
      reported in the literature. We report a case of giant cemento-ossifying fibroma
      of the mandible in a 34 year old female patient. 

PMID- 24678227
TI  - Oral myiasis involving palatal mucosa of a young female.
AB  - In literal terms myiasis is the invasion of the tissues and organs of human
      beings by fly larvae. This phenomenon is well documented in the skin, especially
      among animals and people in developed and developing countries. When the tissues
      of oral cavity are invaded by the parasitic larvae of flies, the condition is
      called as oral myiasis. With the paper we are presenting a case of 19-year-old
      female suffering from oral myiasis of upper lip and palate. The treatment
      consisted of manual removal of the larvae, surgical debridement of the wound and
      oral therapy with doxycycline used as a locally acting drug for faster and better
      recovery. 

PMID- 24678228
TI  - Lymphocutaneous nocardiosis caused by Nocardia otitidiscaviarum: A case report
      and review of literature.
AB  - Nocardia otitidiscaviarum is a rare clinical isolate of primary cutaneous
      infections. This report describes a case of lymphocutaneous nocardiosis caused by
      N. otitidiscaviarum. Analysis of 16S ribosomal RNA gene of the isolate and the
      type strain of N. otitidiscaviarum DSM 43242 showed 100% similarity. The partial
      gene sequence of 1439 bp was submitted to GenBank. (EU031786). The isolate was
      susceptible only to amikacin, minocycline, linezolid and resistant to remaining
      other routine anti-nocardial drugs. The patient was free of nocardiosis after 12
      weeks of treatment with amikacin and linezolid. We reviewed four other cases of
      lymphocutaneous nocardiosis caused by N. otitidiscaviarum. 

PMID- 24678229
TI  - Spontaneous pneumomediastinum with pneumopericardium, surgical emphysema,
      pneumothorax, and epidural pneumotosis: A rare association.
AB  - Pneumomediastinum is usually associated with subcutaneous emphysema and
      pneumopericardium, but rarely associated with pneumothorax and epidural
      pneumotosis. We report extremely rare simultaneous occurrence of self-limiting
      pneumomediastinum, pneumopericardium, surgical emphysema, pneumothorax, and
      epidural pneumotosis in an 18-year-old gentleman in the absence of identifiable
      cause. 

PMID- 24678230
TI  - Laparoscopic appendectomy for mucocele of the appendix.
AB  - Mucocele of the appendix is an aseptic dilatation secondary to obstruction. The
      preoperative clinical diagnosis of appendiceal mucoceles can therefore be
      difficult because of this lack of clinical symptomotology. Surgical excision is
      the treatment of choice in benign mucocele. We report a case presenting to the
      surgeons where initial clinical findings and investigations suggested a cyst in
      the right adnexa. Diagnostic laparoscopy revealed mucocele of the appendix and
      laparoscopic appendicectomy was done. 

PMID- 24678231
TI  - Delivery after augmentation cystoplasty: Implications and precautions.
AB  - A young female with history of genitourinary tuberculosis with solitary
      functioning kidney became pregnant 1 year after augmentation cystoplasty (AC)
      with ureteric reimplantation. Throughout pregnancy she had two episode of febrile
      urinary tract infection. Her renal function remained normal. She was planned for
      cesarian section due to obstetric indications. Despite altered pelvic anatomy, we
      successfully did the lower segment cesarian section. We reviewed the literature
      regarding pregnancy in patients with AC to find that what the treating Urologist
      and Gynecologist should know about these rare cases. Various complications which
      should be anticipated and measures to prevent them are also discussed. 

PMID- 24678232
TI  - External cervical resorption case report and a brief review of literature.
AB  - External cervical resorption (ECR) is the loss of dental hard tissue as a result
      of odontoclastic action; it usually begins on the cervical region of the root
      surface of the teeth. The etiology, predisposing factors, diagnosis, and
      management of ECR have been reviewed here. Effective management and appropriate
      treatment can only be carried out if the true nature and exact location of the
      ECR lesion are known. This paper reports on the management of a case of external
      cervical root resorption (ECRR), which involved root canal treatment and removal
      of the resorbing area of the affected tooth as well as filling the resorbed area
      with mineral trioxide aggregate (MTA) and resin-modified glass ionomer filling
      material (RMGIC). The defect was filled with bone graft material and guided
      tissue regeneration (GTR) membrane. This case highlights the importance of using
      MTA and successful management of cervical resorption with a stable uneventful
      clinical recovery. 

PMID- 24678233
TI  - Low grade endometrial stromal sarcoma in a premenopausal woman.
AB  - Endometrial stromal sarcoma are rare malignant tumors of the uterus and has been
      described as the second most common malignant uterine mesenchymal tumor. The
      diagnosis is confirmed on hysterectomy for a presumed benign disease. In the
      latest World Health Organization (WHO) classification (2003), the term
      endometrial stromal tumor is applied to neoplasms typically composed of cells
      that morphologically resemble endometrial stromal cells of the nonneoplastic
      proliferative phase endometrium. The WHO recognizes three categories of
      endometrial stromal tumors: Endometrial stromal nodule, low-grade endometrial
      stromal sarcomas (LGESS), and undifferentiated endometrial sarcoma. We report
      here an interesting case of a 39-year-old female who presented with irregular
      bleeding per vaginum and urinary retention with a clinical impression of a
      leiomyomatous polyp, which on histological examination showed a LGESS. 

PMID- 24678234
TI  - Dens invagination: A review of literature and report of two cases.
AB  - Dens invaginatus occurs as a result of the invagination of the enamel organ.
      These cases may present difficulties with respect to its diagnosis and treatment
      because of canal morphology. It frequently leads to caries, pulpal, and
      periodontal involvement with necrosis and loss of attachment. The knowledge of
      classification and anatomical variations of teeth with dens invaginatus are of
      great importance for correct treatment. This article presents two case reports of
      two different types of dens invaginatus along with profound review of the
      literature regarding etiology, epidemiology, and histology. It discusses clinical
      appearance and diagnosis, and it provides guidelines for decision-making and
      treatment of invaginated teeth. 

PMID- 24678236
TI  - Stress fracture of ulna due to excessive push-ups.
AB  - Stress fractures are most common in the weight-bearing bones of the lower
      extremities and spine, but are rarely found in non-weight-bearing bones of the
      body. Stress fracture of the ulna is extremely rare. We report a case of complete
      stress fracture of ulna caused due to excessive push ups in a young athlete.
      Conservative management was successful in healing of fracture and returning this
      patient back to his previous activity level. Physician should have high index of
      suspicion, whenever they encounter a young athlete complaining of forearm pain. 

PMID- 24678235
TI  - Oral rhabdomyosarcoma-embryonal subtype in an adult: A rarity.
AB  - Rhabdomyosarcoma is a malignant tumor composed of neoplastic mesenchymal cells,
      with varying degrees of striated muscle cell differentiation. With most cases
      occurring in children younger than 10 years, it is remarkably rare in adults.
      Further in adults, the typical pediatric rhabdomyosarcoma variants (embryonal and
      alveolar sub-types) occur less frequently and exhibit predilection for viscera
      followed by the head and neck region. A rare case of embryonal rhabdomyosarcoma
      arising from the buccal mucosa in a 36-year old male patient is herewith
      reported. Recognition of the correct diagnosis and histological sub-type is of
      critical importance in the therapy of this disease, since the treatment is not
      uniform in the literature because of the rarity of this neoplasm in the adult
      population. 

PMID- 24678237
TI  - Study of life expectancy in urban Pondicherry.

PMID- 24678238
TI  - High-Dimensional Longitudinal Genomic Data: An analysis used for monitoring viral
      infections.

PMID- 24678239
TI  - A facile microwave-assisted protocol for rapid synthesis of N-acetylneuraminic
      acid congeners.
AB  - We developed a simple, rapid and efficient microwave irradiation-assisted
      protocol that is 1- to 2-orders of magnitude faster than conventional techniques,
      providing an expedient access to the sialic acid congeners Neu5Ac1Me (1),
      Neu5Acbeta1,2Me2 (2), Neu5Ac1Me O-peracetate (3) and 4,5-oxazoline of
      Neu5Ac2en1Me O-peracetate (4).

PMID- 24678240
TI  - Comment on "validation of a blood-based laboratory test to aid in the
      confirmation of a diagnosis of schizophrenia".
AB  - COMMENT ON: Schwarz et al. Validation of a Blood-Based Laboratory Test to Aid in
      the Confirmation of a Diagnosis of Schizophrenia. Biomarker Insights. 2010:5 39
      47 doi:10.4137/BMI.S4877.

PMID- 24678242
TI  - Host Cell Reactivation and Transcriptional Activation of Carboplatin-Modified
      BRCA1.
AB  - The breast cancer susceptibility gene 1 (BRCA1) has been shown to maintain
      genomic stability through multiple functions in the regulation of DNA damage
      repair and transcription. Its translated BRCT (BRCA1 C-terminal domain) acts as a
      strong transcriptional activator. BRCA1 damaged by carboplatin treatment may lead
      to a loss of such functions. To address the possibility of the BRCA1 gene as a
      therapeutic target for carboplatin, we investigated the functional consequences
      of the 3'-terminal region of human BRCA1 following in vitro platination with
      carboplatin. A reduction in cellular BRCA1 repair of carboplatin-treated plasmid
      DNA, using a host cell reactivation assay, was dependent on the platination
      levels on the reporter gene. The transcriptional transactivation activity of the
      drug-modified BRCA1, assessed using a one-hybrid GAL4 transcriptional assay, was
      inversely proportional to the carboplatin doses. The data emphasized the
      potential of the BRCA1 gene to be a target for carboplatin treatment. 

PMID- 24678241
TI  - Novel PI3K and mTOR Inhibitor NVP-BEZ235 Radiosensitizes Breast Cancer Cell Lines
      under Normoxic and Hypoxic Conditions.
AB  - In the present study, we assessed, if the novel dual phosphatidylinositol 3
      kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235
      radiosensitizes triple negative (TN) MDA-MB-231 and estrogen receptor (ER)
      positive MCF-7 cells to ionizing radiation under various oxygen conditions,
      simulating different microenvironments as occurring in the majority of breast
      cancers (BCs). Irradiation (IR) of BC cells cultivated in hypoxic conditions
      revealed increased radioresistance compared to normoxic controls. Treatment with
      NVP-BEZ235 completely circumvented this hypoxia-induced effects and
      radiosensitized normoxic, reoxygenated, and hypoxic cells to similar extents.
      Furthermore, NVP-BEZ235 treatment suppressed HIF-1alpha expression and PI3K/mTOR
      signaling, induced autophagy, and caused protracted DNA damage repair in both
      cell lines in all tested oxygen conditions. Moreover, after incubation with NVP
      BEZ235, MCF-7 cells revealed depletion of phospho-AKT and considerable signs of
      apoptosis, which were significantly enhanced by radiation. Our findings clearly
      demonstrate that NVP-BEZ235 has a clinical relevant potential as a
      radiosensitizer in BC treatment. 

PMID- 24678243
TI  - Desmoid tumor in puerperium period: a case report.
AB  - Desmoid tumors (DTs) are rare tumors classified as deep fibromatoses taking
      origin from fascial or musculoaponeurotic structures. With pregnancy and surgical
      scars considered in the etiology, most anterior abdominal wall DTs occur in women
      in their reproductive years, especially during a pregnancy or post-partum.
      Herein, we present development of DT in a female patient in the post-partum
      period following cesarean delivery, which manifested itself with a growing mass
      in anterior abdominal wall. In our case, possibility of hematoma most probably
      located beneath the fascia was considered initially as a complication of cesarean
      section based on ultrasonographic examination and location of the lesion, while
      upon lack of either spontaneous regression with eventual diminish in size or
      resolve of symptoms within six weeks, further investigation via MRI and tru-cut
      biopsy revealed the diagnosis of abdominal DT. Radical tumor extirpation with
      resection of an adequate margin of surrounding normal tissue was applied, and the
      post-operative period was uneventful. 

PMID- 24678244
TI  - Successful revascularization to right coronary artery by percutaneous coronary
      intervention after endovascular therapy for leriche syndrome.
AB  - A 69-year-old man with effort angina was admitted to our institution.
      Echocardiography showed poor left ventricular systolic function with akinesis of
      the anterior wall and severe hypokinesis of the inferior wall. We performed
      coronary angiography, which revealed two diseased vessels including chronic total
      occlusion in the left anterior descending artery and severe stenosis in the right
      coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive
      disease known as Leriche syndrome. As the patient's symptom was stable, we first
      planned to perform endovascular therapy (EVT) for Leriche syndrome to make a
      route for intra-aortic balloon pumping. We prepared a bi-directional approach
      from bi-femoral arteries and a left brachial artery. The guidewire was passed
      through the occlusive area using the retrograde approach. The self-expanding
      stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath
      was inserted from the right radial artery and an intra-aortic balloon pump was
      successfully inserted through the right femoral artery for percutaneous coronary
      intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed
      to RCA after using an atherectomy device (rotablator). We reported the case as a
      successfully performed PCI to the RCA after EVT for Leriche syndrome. 

PMID- 24678245
TI  - Hormonal Therapeutics Enzalutamide and Abiraterone Acetate in the Treatment of
      Metastatic Castration-Resistant Prostate Cancer (mCRPC) Post-docetaxel-an
      Indirect Comparison.
AB  - INTRODUCTION: This study aims to make an indirect comparison between enzalutamide
      and abiraterone acetate for mCRPC post-docetaxel. METHODS: A search for published
      phase 3 trials was performed with PubMed. Indirect comparisons of enzalutamide
      (AFFIRM) to abiraterone acetate (COU-AA-301) on outcomes overall survival (OS),
      time to prostate-specific-antigen (PSA) progression, radiographic progression
      free survival (PFS), and PSA response were constructed in the context of log
      linear regression models. RESULTS: There was no statistically significant
      difference in OS (hazard ratio (HR) 0.85, 95% CI 0.68-1.07). However, there was
      some evidence that enzalutamide may outperform abiraterone acetate with respect
      to secondary outcomes: time to PSA progression (HR 0.40, 95% CI 0.30-0.53),
      radiographic PFS (HR 0.61, 95% CI 0.50-0.74), and PSA response rates (RRs) (OR
      10.69, 95% CI 3.92-29.20). CONCLUSION: While there was no statistically
      significant difference in OS, enzalutamide may be advantageous for secondary
      endpoints. Findings of this indirect comparison serve to be hypothesis-generating
      for future head-to-head trials.

PMID- 24678246
TI  - Molecular insights into systemic lupus erythematosus pathogenesis.

PMID- 24678247
TI  - Exposure to lipophilic chemicals as a cause of neurological impairments,
      neurodevelopmental disorders and neurodegenerative diseases.
AB  - Many studies have associated environmental exposure to chemicals with
      neurological impairments (NIs) including neuropathies, cognitive, motor and
      sensory impairments; neurodevelopmental disorders (NDDs) including autism and
      attention deficit hyperactivity disorder (ADHD); neurodegenerative diseases
      (NDGs) including Alzheimer's disease, Parkinson's disease and amyotrophic lateral
      sclerosis (ALS). The environmental chemicals shown to induce all these diseases
      include persistent organic pollutants (POPs), the plastic exudates bisphenol A
      and phthalates, low molecular weight hydrocarbons (LMWHCs) and polynuclear
      aromatic hydrocarbons (PAHs). It is reported here that though these chemicals
      differ widely in their chemical properties, reactivities and known points of
      attack in humans, a common link does exist between them. All are lipophilic
      species found in serum and they promote the sequential absorption of otherwise
      non-absorbed toxic hydrophilic species causing these diseases. 

PMID- 24678250
TI  - Hemolytic activity and platelet aggregation inhibitory effect of vipoxin's basic
      sPLA2 subunit.
AB  - In the present study we evaluated the effect of secreted phospholipase A2 (sPLA2)
      (the toxic subunit of the heterodimeric neurotoxin vipoxin, isolated from the
      Bulgarian long-nosed viper Vipera ammodytes meridionalis) on hemolysis,
      erythrocyte morphology and platelet aggregation. Hemolytic activity of sPLA2 was
      examined in the presence of saturated (palmitic) and unsaturated (oleic) fatty
      acids and it was found that oleic acid increased the hemolytic activity of sPLA2
      in a concentration-dependent manner, compared to the effect of palmitic acid and
      controls. The addition of heparin to red blood cells (RBC) suspension containing
      sPLA2 or mixture of sPLA2 and the corresponding fatty acid led to an inhibition
      of hemolytic activity. The effect of sPLA2 on RBC morphology resulted in
      formation of echinocytes (spherocyte subtype), suggesting that RBC could be the
      possible targets attacked by sPLA2. Vipoxin sPLA2 inhibited (in a dose-dependent
      manner) platelet aggregation when arachidonic acid and collagen were used as
      inducers, while in the case of ADP its inhibitory effect was inappreciable. 

PMID- 24678249
TI  - Determination of motor activity and anxiety-related behaviour in rodents:
      methodological aspects and role of nitric oxide.
AB  - In various areas of the bio-medical, pharmacological and psychological research a
      multitude of behavioural tests have been used to investigate the effects of
      environmental, genetic and epi-genetic factors as well as pharmacological
      substances or diseased states on behaviour and thus on the physiological and
      psycho-social status of experimental subjects. This article is reviewing the most
      frequently used behavioural tests in animal research (open field, elevated plus
      maze, zero maze, and black and white box). It provides a summary of common
      characteristics as well as differences in the methods used in various studies to
      determine motor activity, anxiety and emotionality. Additionally to
      methodological aspects, strain, sex and stress-related differences as well as the
      involvement of nitric oxide in modulation of motor activity and anxiety of
      rodents were briefly reviewed. 

PMID- 24678251
TI  - Analysis of non-steroidal anti-inflammatory drug use in hospitalized patients and
      perception of their risk.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the most widely
      prescribed and used pharmacological agents worldwide. Data gathered in the last
      decade show increased incidence of thrombotic events during NSAID administration.
      Analysis of NSAID usage and assessment of risk for development of cardiovascular
      adverse effects is needed for improving patient safety. For limiting the impact
      of adverse effects on the health of patients, NSAID users should be informed
      about the possible adverse effects and their symptoms to ensure early detection
      and treatment discontinuation. In the presented study, we retrospectively
      analyzed the administration of NSAIDs in a group of patients (n=428) in need of
      analgesic treatment hospitalized at a department of internal medicine. Factors
      increasing the risk for cardiovascular adverse effects were also investigated. A
      separate questionnaire study was conducted to gather information concerning the
      knowledge of hospitalized NSAID users (n=251) about adverse effects of the
      medication used. For purpose of comparison, we conducted a similar study in a
      group of 234 random respondents from a shopping center. Data were evaluated using
      descriptive statistics, Student's t-test and chi-squared test. Our results
      suggest that the majority of patients treated with NSAIDs have factors indicating
      increased risk of development of adverse effects, most commonly arterial
      hypertension (58.2% of patients). The results of our questionnaire study show
      limited knowledge of NSAID users about the risk of the therapy. Nearly half of
      the respondents were unaware of any adverse effects. We consider as alarming that
      only a limited number of respondents were informed by their physician or
      pharmacist about the possible risks of treatment. In conclusion, we found that
      hospitalized NSAID users often have a history of diseases predisposing to the
      development of cardiovascular adverse effects of NSAIDs. Despite this, their
      knowledge about the risk of treatment is insufficient. 

PMID- 24678252
TI  - Phytochemical and acute toxicity of ethanolic extract of Enantia chlorantha
      (oliv) stem bark in albino rats.
AB  - It is presumed that drugs sourced from herbs have lesser side effects than
      allopathic drugs. Enantia chlorantha is widely used in herbal medicine for the
      treatment of several ailments such as jaundice, malaria, fever, infective
      hepatitis, etc. However its toxicity profiles are not well documented. The
      effects of ethanolic extract of E. chlorantha stem bark on body weight changes,
      biochemical and haematological parameters as well as histology of vital organs
      (heart, kidneys and liver) were assessed. Also, the phytochemical constituent of
      the plant was analysed. Albino rats of both sexes were randomly divided into five
      groups (A-E) of five rats each and the ethanolic extract of E. chlorantha stem
      bark extract was administered by oral gavage in a single dose. Group A rats were
      administered 500 mg/kg of the extract, group B; 1000 mg/kg, group C; 2000 mg/kg,
      group D; 3000 mg/kg and group E rats received distilled water (10 ml/kg) and
      served as control. The extract caused significant (p<0.05) decreases in the
      levels of packed cell volume, haemoglobin concentration and red blood cell counts
      in a dose dependent manner. Further, significant alterations were not observed in
      the serum biochemical parameters analysed (AST, ALP, ALT, blood urea nitrogen,
      total protein, albumin, globulin and bilirubin). In addition, the extract at
      1000, 2000 and 3000 mg/kg caused congestion in the heart and kidney of
      experimental rats. These results suggest that oral administration of E.
      chlorantha may produce severe toxic effects at relatively high doses, thus
      caution should be exercised in its use. 

PMID- 24678248
TI  - Hyaluronan and synovial joint: function, distribution and healing.
AB  - Synovial fluid is a viscous solution found in the cavities of synovial joints.
      The principal role of synovial fluid is to reduce friction between the articular
      cartilages of synovial joints during movement. The presence of high molar mass
      hyaluronan (HA) in this fluid gives it the required viscosity for its function as
      lubricant solution. Inflammation oxidation stress enhances normal degradation of
      hyaluronan causing several diseases related to joints. This review describes
      hyaluronan properties and distribution, applications and its function in synovial
      joints, with short review for using thiol compounds as antioxidants preventing HA
      degradations under inflammation conditions. 

PMID- 24678253
TI  - Evaluation of hepatic antioxidant capacities of Spirogyra neglecta (Hassall)
      Kutzing in rats.
AB  - Free radicals are one of the causes of chronic and degenerative diseases.
      Antioxidants can protect the progression of free radical mediated disorders. The
      aim of this study was to evaluate the antioxidant activity of Spirogyra neglecta
      (Hassall) Kutzing in rats. The rats were divided into 5 groups. Group 1 served as
      control. Groups 2 and 3 were administered hot water extract of S. neglecta at 50
      and 200 mg/kg bw, respectively, while groups 4 and 5 were fed 1% and 4% S.
      neglecta mixed diet, resp., for 13 weeks. Antioxidant enzymes were evaluated in
      livers of the rats. The activities of catalase and glutathione reductase were
      significantly increased in the group fed 50 mg/kg of the extract, compared with
      the control group. Glutathione peroxidase activity was also significantly higher
      in the group fed 50 and 200 mg/kg of the extract. The study suggests that S.
      neglecta may enhance antioxidant systems in the rat liver. 

PMID- 24678254
TI  - Effects of cadmium chloride on mouse inner medullary collecting duct cells.
AB  - Cadmium is a known renal toxin. The cytotoxic effect of cadmium chloride (CdCl2)
      was evaluated on renal inner medullary collecting duct cells (mIMCD3). The 24 hr
      LC50 value for CdCl2 in mIMCD3 cells was 40 uM. The present study showed that
      mIMCD3 cells were sensitive to CdCl2 exposure. 

PMID- 24678256
TI  - Pilot study on agricultural pesticide poisoning in Burkina Faso.
AB  - Epidemiologic data related to agricultural pesticide poisoning cases in Burkina
      Faso were collected. The study was carried out using retrospective (from January
      2002 to June 2010) surveys conducted among farmers and healthcare centers. One
      hundred and fifty-three (153) pest control products were recorded during the
      survey and 56 active ingredients were identified. Out of the 153 pest control
      products, 49 (i.e. 32%) were authorized for sale in Burkina Faso. The main risk
      factors are socio-demographic characteristics of farmers, their low education
      level, and some attitudes and practices on using agricultural pesticides.
      Pesticide poisonings are relatively frequent and their management was not always
      efficacious. Actions are needed to reduce pesticide poisoning as a global public
      health problem and to improve management of pesticide poisoning. To this purpose,
      advanced investigations should be carried out over a longer period of time to
      complement the present pilot study. 

PMID- 24678257
TI  - Testicular membrane lipid damage by complex mixture of leachate from municipal
      battery recycling site as indication of idiopathic male infertility in rat.
AB  - Leachate from a municipal battery recycling site is a potent source of mixed
      metal released into the environment. The present study investigated the degree at
      which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to
      the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected
      the lipid membrane of the testes in in vitro experiment. The results showed
      elevated level of mixed-metals over the permissible levels in drinking water, as
      recommended by regulatory authorities. In the leachate samples, the levels of
      malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05)
      increased in rat testes in a dose-dependent manner. MDA induced by the municipal
      auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate
      from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular
      lipid membrane capacity was compromised following treatment with leachate from
      the municipal battery recycling site, implicating mixed-metal exposure as the
      causative agent of testicular damage and male infertility. 

PMID- 24678258
TI  - Sulfur mustard induced oxidative stress and its alteration using asoxime (HI-6).
AB  - Sulfur mustard (SM) is a blister agent with cytotoxic mechanism of action. There
      is no suitable treatment based on administration of an antidote. In this study,
      Wistar rats were exposed to SM in doses of 0-40 mg/kg body weight and treated
      with the compound HI-6. The treatment provided no significant effect on ferric
      reducing antioxidant power of blood and plasma. However, HI-6 caused an increase
      in the level of thiobarbituric acid reactive substances. This stressogenic
      response was presumably the cause of the significant elevation of the blood level
      of both glutathione reductase and reduced glutathione. HI-6 appears to be
      suitable for enhancing prophylactically oxidative stress protection from small
      oxidative insult. 

PMID- 24678255
TI  - Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance.
AB  - Celiac disease, and, more generally, gluten intolerance, is a growing problem
      worldwide, but especially in North America and Europe, where an estimated 5% of
      the population now suffers from it. Symptoms include nausea, diarrhea, skin
      rashes, macrocytic anemia and depression. It is a multifactorial disease
      associated with numerous nutritional deficiencies as well as reproductive issues
      and increased risk to thyroid disease, kidney failure and cancer. Here, we
      propose that glyphosate, the active ingredient in the herbicide, Roundup((r)), is
      the most important causal factor in this epidemic. Fish exposed to glyphosate
      develop digestive problems that are reminiscent of celiac disease. Celiac disease
      is associated with imbalances in gut bacteria that can be fully explained by the
      known effects of glyphosate on gut bacteria. Characteristics of celiac disease
      point to impairment in many cytochrome P450 enzymes, which are involved with
      detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A,
      and maintaining bile acid production and sulfate supplies to the gut. Glyphosate
      is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt,
      molybdenum, copper and other rare metals associated with celiac disease can be
      attributed to glyphosate's strong ability to chelate these elements. Deficiencies
      in tryptophan, tyrosine, methionine and selenomethionine associated with celiac
      disease match glyphosate's known depletion of these amino acids. Celiac disease
      patients have an increased risk to non-Hodgkin's lymphoma, which has also been
      implicated in glyphosate exposure. Reproductive issues associated with celiac
      disease, such as infertility, miscarriages, and birth defects, can also be
      explained by glyphosate. Glyphosate residues in wheat and other crops are likely
      increasing recently due to the growing practice of crop desiccation just prior to
      the harvest. We argue that the practice of "ripening" sugar cane with glyphosate
      may explain the recent surge in kidney failure among agricultural workers in
      Central America. We conclude with a plea to governments to reconsider policies
      regarding the safety of glyphosate residues in foods. 

PMID- 24678259
TI  - Modulation of keratin 1, 10 and involucrin expression as part of the complex
      response of the human keratinocyte cell line HaCaT to ultraviolet radiation.
AB  - Skin exposure to ultraviolet (UV) light evokes a complex stress response in
      keratinocytes. Keratin filament organization provides structural stability and
      mechanical integrity of keratinocytes. Involucrin is a transglutaminase substrate
      protein contributing to the formation of insoluble cornified envelopes. However,
      a more complex role for keratins and involucrin has been proposed, including the
      regulation of cell stress response. The aim was to evaluate modulations of
      keratin 1, 10 and involucrin expression in HaCaT in the light of the complex
      response of these cells to UV-B radiation, including effects on c-Jun and matrix
      metalloproteinase 1 (MMP-1) gene expression and production of interleukin (IL) 6
      and 8. A UV-B (300+/-5 nm) dose of 10 mJ/cm(2) was selected since this dose
      resulted in a partial decrease in cell viability in contrast to higher UV-B
      doses, which induced complete cell death 48 h after treatment. The UV-B radiation
      induced significant expression of keratin 1 and 10 and decreased expression of
      involucrin. This was accompanied by increased expression of c-Jun and MMP-1 and
      IL-6 and IL-8 production. The data suggest that the expression of keratin 1, 10
      and involucrin is modulated in HaCaT keratinocytes as a part of the complex
      stress response to UV radiation. 

PMID- 24678260
TI  - Antioxidant action and cytotoxicity on HeLa and NIH-3T3 cells of new quercetin
      derivatives.
AB  - Quercetin is a natural polyphenol with proven health beneficial activities. In
      this study 15 new quercetin derivatives were prepared with the aim to enhance
      their bioavailability. Modification of their physicochemical properties could
      herewith improve the action in cells. The prepared compounds were tested for
      their antioxidant and cytotoxic activity. The ability to scavenge free radicals
      as well as ferric reducing antioxidant power of the new derivatives was not
      better than that of unmodified quercetin. But for acetylated esters a better
      cytotoxic activity was found on human cervical cancer cells HeLa than for the
      initial molecule. The best effect revealed chloronaphtoquinone quercetin
      (IC50=13.2 uM). For this compound comparable cytotoxic action on non-cancer
      murine fibroblast cells was detected (IC50=16.5 uM). The obtained results
      indicate that appropriate lipophilization of the quercetin molecule could improve
      its cytotoxic action in cells, probably due to its enhanced bioavailability. 

PMID- 24678261
TI  - The ameliorative effect of ascorbic acid and Ginkgo biloba on learning and memory
      deficits associated with fluoride exposure.
AB  - Chronic exposure to fluoride causes dental and skeletal fluorosis. Fluoride
      exposure is also detrimental to soft tissues and organs. The present study aimed
      at evaluation of the effect of Ginkgo biloba and ascorbic acid on learning and
      memory deficits caused by fluoride exposure. Male Wistar rats were divided into
      five groups (n=6). Group 1 control. Groups 2 to 5 received 100 ppm of sodium
      fluoride over 30 days. Groups 3, 4 and 5 were further treated for 15 days
      receiving respectively 1% gum acacia solution, 100 mg/kg body weight ascorbic
      acid, and 100mg/kg body weight Ginkgo biloba extract. After 45 days, all animals
      were subjected to behavioural tests. The results showed that fluoride affected
      learning and memory. Fluoride causes oxidative stress and neurodegeneration,
      thereby affecting learning and memory. Ascorbic acid and Ginkgo biloba were found
      to augment the reversal of learning and memory deficits caused by fluoride
      ingestion. 

PMID- 24678262
TI  - Habituation of exploratory behaviour in VPA rats: animal model of autism.
AB  - Autism is a neurodevelopmental disorder with multifactorial aetiology,
      represented as impairment in social behaviour, communication and the occurrence
      of repetitive activities, which can be observed in the early life. The core
      features are frequently accompanied by other manifestations, including limited
      environmental exploration. The aim of the presented study, realised on an animal
      model of autism - VPA rats, i.e. animals prenatally affected with valproic acid
      on gestation day 12.5, was to investigate the habituation process of exploratory
      activity (manifested by a gradual decrease in the intensity of locomotor
      activity), which reflects the stage of the central nervous system. VPA rats were
      tested in open-field in three developmental periods - weaning (postnatal day 21 -
      PND 21), puberty (PND 42) and adulthood (PND 72). In each period of ontogenesis,
      the rapidity of habituation was evaluated by using the method of linear
      regression. Compared to controls, VPA rats showed a significant decrease in the
      intensity and an increase in the rapidity of exploratory activity habituation
      during puberty and adulthood. Our results indicate that the animal model of
      autism, i.e. VPA rats, showed disabilities in the development of the nervous
      system. These findings can help confirm not only the validity of this animal
      model of autism but can also help better understand neuronal changes in humans
      with autism. 

PMID- 24678263
TI  - Usability and Feasibility of an Internet-Based Virtual Pedestrian Environment to
      Teach Children to Cross Streets Safely.
AB  - Child pedestrian injury is a preventable global health challenge. Successful
      training efforts focused on child behavior, including individualized streetside
      training and training in large virtual pedestrian environments, are laborious and
      expensive. This study considers the usability and feasibility of a virtual
      pedestrian environment "game" application to teach children safe street-crossing
      behavior via the internet, a medium that could be broadly disseminated at low
      cost. Ten 7- and 8-year-old children participated. They engaged in an internet
      based virtual pedestrian environment and completed a brief assessment survey.
      Researchers rated children's behavior while engaged in the game. Both self-report
      and researcher observations indicated the internet-based system was readily used
      by the children without adult support. The youth understood how to engage in the
      system and used it independently and attentively. The program also was feasible.
      It provided multiple measures of pedestrian safety that could be used for
      research or training purposes. Finally, the program was rated by children as
      engaging and educational. Researcher ratings suggested children used the program
      with minimal fidgeting or boredom. The pilot test suggests an internet-based
      virtual pedestrian environment offers a usable, feasible, engaging, and
      educational environment for child pedestrian safety training. If future research
      finds children learn the cognitive and perceptual skills needed to cross streets
      safely within it, internet-based training may provide a low-cost medium to
      broadly disseminate child pedestrian safety training. The concept may be
      generalized to other domains of health-related functioning such as teen driving
      safety, adolescent sexual risk-taking, and adolescent substance use.

PMID- 24678264
TI  - Comparative analysis of the methanogen diversity in horse and pony by using mcrA
      gene and archaeal 16s rRNA gene clone libraries.
AB  - Comparative analysis of methanogen compositions in the feces of horse and pony
      was carried out by constructing the alpha -subunit of methyl coenzyme-M reductase
      (mcrA) gene and 16S ribosomal RNA gene (16S rRNA) clone libraries. The mcrA clone
      library analysis indicated that Methanomicrobiales was predominant in both horse
      and pony. Furthermore, most of the clones of the 16S rRNA gene library showed
      that Methanomicrobiales was also predominant in horse and pony, but the LIBSHUFF
      analysis showed that the horse and pony libraries were significantly different (P
      < 0.05). Most of operational taxonomic units (OTUs) showed low similarity to the
      identified methanogens in both the mcrA and the 16S rRNA clone libraries. The
      results suggest that horse and pony harbor unidentified and novel methanogens in
      their hindgut. The methanogen population was higher in horse than in pony;
      however, the anaerobic fungal population was similar in horse and pony. The
      methanogen diversity was different between two breeds of Equus caballus. 

PMID- 24678265
TI  - Early methanogenic colonisation in the faeces of Meishan and Yorkshire piglets as
      determined by pyrosequencing analysis.
AB  - Gut methanogenic archaea of monogastric animals are considered to be related to
      energy metabolism and adipose deposition of the host; however, information on
      their development in young piglets is limited. Thus, to investigate early
      methanogenic colonisation in the faeces of Meishan and Yorkshire piglets, faecal
      samples were collected from piglets at 1, 3, 7, and 14 days after birth and used
      to analyse the methanogenic community with 16S rRNA gene pyrosequencing. Results
      showed that the diversity of the methanogenic community in the faeces of neonatal
      piglets decreased from one to 14 days of age, as the total methanogen populations
      increased. The age of piglets, but not the breed, significantly affected the
      diversity of the methanogenic community which was dominated by the genus
      Methanobrevibacter. From the ages of one to 14 days, the abundance of M. smithii
      related operational taxonomic units (OTUs) increased significantly, while the
      abundances of M. thaueri- and M. millerae-related OTUs decreased significantly.
      The substitution of M. smithii for M. thaueri/M. millerae was faster in Yorkshire
      piglets than in Meishan piglets. These results suggest that the early
      establishment of microbiota in neonatal piglets is accompanied by dramatic
      changes in the methanogenic community, and that the changes vary among pigs of
      different genotypes. 

PMID- 24678266
TI  - Development of beta -lactamase as a tool for monitoring conditional gene
      expression by a tetracycline-riboswitch in Methanosarcina acetivorans.
AB  - The use of reporter gene fusions to assess cellular processes such as protein
      targeting and regulation of transcription or translation is established
      technology in archaeal, bacterial, and eukaryal genetics. Fluorescent proteins or
      enzymes resulting in chromogenic substrate turnover, like beta -galactosidase,
      have been particularly useful for microscopic and screening purposes. However,
      application of such methodology is of limited use for strictly anaerobic
      organisms due to the requirement of molecular oxygen for chromophore formation or
      color development. We have developed beta -lactamase from Escherichia coli
      (encoded by bla) in conjunction with the chromogenic substrate nitrocefin into a
      reporter system usable under anaerobic conditions for the methanogenic archaeon
      Methanosarcina acetivorans. By using a signal peptide of a putative flagellin
      from M. acetivorans and different catabolic promoters, we could demonstrate
      growth substrate-dependent secretion of beta -lactamase, facilitating its use in
      colony screening on agar plates. Furthermore, a series of fusions comprised of a
      constitutive promoter and sequences encoding variants of the synthetic
      tetracycline-responsive riboswitch (tc-RS) was created to characterize its
      influence on translation initiation in M. acetivorans. One tc-RS variant resulted
      in more than 11-fold tetracycline-dependent regulation of bla expression, which
      is in the range of regulation by naturally occurring riboswitches. Thus, tc-RS
      fusions represent the first solely cis-active, that is, factor-independent system
      for controlled gene expression in Archaea. 

PMID- 24678267
TI  - Axonal tract tracing for delineating interacting brain regions: implications for
      Alzheimer's disease-associated memory.
AB  - We are studying the projections from the entorhinal cortex to the hippocampal
      formation in the mouse. The dentate gyrus is innervated by the lateral entorhinal
      cortex (lateral perforant path) and medial entorhinal cortex (medial perforant
      path). The entorhinal cortex also projects to hippocampal areas CA3 and CA1, and
      to the subiculum. In young transgenic Alzheimer's disease mouse models (before
      amyloid-beta pathology), the connections are not different from normal mice. In
      Alzheimer's disease mice with pathology, two changes occur: first, dystrophic
      axon endings appear near amyloid-beta plaques, and second, there are sparse
      aberrant axon terminations not in the appropriate area or lamina of the
      hippocampus. Furthermore, MRI-diffusion tensor imaging analysis indicates a
      decrease in the quality of the white matter tracts connecting the hippocampus to
      the brain; in other words, the fimbria/fornix and perforant path. Similar changes
      in white matter integrity have been found in Alzheimer's disease patients and
      could potentially be used as early indicators of disease onset.

PMID- 24678268
TI  - Evolution of transmission mode in obligate symbionts.
AB  - BACKGROUND: A host obtains symbionts by horizontal transmission when infected
      from the environment or contagiously from other hosts in the same generation. In
      contrast, vertical transmission occurs when a host obtains its symbionts directly
      from its parents. Either vertical or horizontal transmission can sustain an
      association between a host and its symbiont. QUESTIONS: What evolutionary forces
      are necessary to evolve from an ancestral state of horizontal transmission to a
      derived state of vertical transmission? MATHEMATICAL METHODS: We explore a
      general model of fitness interaction, including both additive and epistatic
      effects, between host and symbiont genes. Recursion equations allow us to analyse
      the short-term behaviour of the model and to study long-term deterministic
      effects with numerical iterations. KEY ASSUMPTIONS: Obligate interaction between
      a symbiont and a single host species with genetically determined horizontal and
      vertical transmission. No free-living symbionts or uninfected hosts and each host
      is infected by only a single symbiont genetic lineage (no multiple infections).
      No population structure. CONCLUSIONS: Epistasis for fitness between host and
      symbiont genes, like that in a matching alleles model, is a necessary condition
      for the evolution of vertical from horizontal transmission. Stochastic individual
      based simulations show that (1) mutation facilitates the switch to vertical
      transmission and (2) vertical transmission is a stable evolutionary endpoint for
      a matching alleles model.

PMID- 24678269
TI  - Time-Dependent Solid State Polymorphism of a Series of Donor-Acceptor Dyads.
AB  - In order to exploit the use of favorable electrostatic interactions between
      aromatic units in directing the assembly of donor-acceptor (D-A) dyads, the
      present work examines the ability of conjugated aromatic D-A dyads with symmetric
      side chains to exhibit solid-state polymorphism as a function of time during the
      solid formation process. Four such dyads were synthesized and their packing in
      the solid-state from either slower (10-20 days) or faster (1-2 days) evaporation
      from solvent was investigated using single crystal X-ray analysis and powder X
      ray diffraction. Two of the dyads exhibited tail-to-tail (A-A) packing upon
      slower evaporation from solvent and head-to-tail (D-A) packing upon faster
      evaporation from solvent. A combination of single crystal analysis and XRD
      patterns were used to create models wherein a packing model for the other two
      dyads is proposed. Our findings suggest that while side chain interactions in
      asymmetric aromatic dyads can play an important role in enforcing segregated D-A
      dyad assembly, slowly evaporating symmetrically substituted aromatic dyads allows
      for favorable electrostatic interactions between the aromatic moieties to
      facilitate the organization of the dyads in the solid-state.

PMID- 24678270
TI  - On Efficient Large Margin Semisupervised Learning: Method and Theory.
AB  - In classification, semisupervised learning usually involves a large amount of
      unlabeled data with only a small number of labeled data. This imposes a great
      challenge in that it is difficult to achieve good classification performance
      through labeled data alone. To leverage unlabeled data for enhancing
      classification, this article introduces a large margin semisupervised learning
      method within the framework of regularization, based on an efficient margin loss
      for unlabeled data, which seeks efficient extraction of the information from
      unlabeled data for estimating the Bayes decision boundary for classification. For
      implementation, an iterative scheme is derived through conditional expectations.
      Finally, theoretical and numerical analyses are conducted, in addition to an
      application to gene function prediction. They suggest that the proposed method
      enables to recover the performance of its supervised counterpart based on
      complete data in rates of convergence, when possible.

PMID- 24678271
TI  - Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring
      Lifetime Alcohol Dependence.
AB  - This study examined the influences of parental divorce and maternal-paternal
      histories of alcohol problems on adult offspring lifetime alcohol dependence
      using data from the 2001-2002 National Epidemiological Survey on Alcohol and
      Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol
      problems interacted to differentially influence the likelihood of offspring
      lifetime alcohol dependence. Experiencing parental divorce and either maternal or
      paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce
      and history of alcohol problems for both parents tripled the likelihood.
      Offspring of parental divorce may be more vulnerable to developing alcohol
      dependence, particularly when one or both parents have alcohol problems.

PMID- 24678272
TI  - Augmented lagrange based on modified covariance matching criterion method for DOA
      estimation in compressed sensing.
AB  - A novel direction of arrival (DOA) estimation method in compressed sensing (CS)
      is presented, in which DOA estimation is considered as the joint sparse recovery
      from multiple measurement vectors (MMV). The proposed method is obtained by
      minimizing the modified-based covariance matching criterion, which is acquired by
      adding penalties according to the regularization method. This minimization
      problem is shown to be a semidefinite program (SDP) and transformed into a
      constrained quadratic programming problem for reducing computational complexity
      which can be solved by the augmented Lagrange method. The proposed method can
      significantly improve the performance especially in the scenarios with low signal
      to noise ratio (SNR), small number of snapshots, and closely spaced correlated
      sources. In addition, the Cramer-Rao bound (CRB) of the proposed method is
      developed and the performance guarantee is given according to a version of the
      restricted isometry property (RIP). The effectiveness and satisfactory
      performance of the proposed method are illustrated by simulation results. 

PMID- 24678273
TI  - Inferential statistics from Black Hispanic breast cancer survival data.
AB  - In this paper we test the statistical probability models for breast cancer
      survival data for race and ethnicity. Data was collected from breast cancer
      patients diagnosed in United States during the years 1973-2009. We selected a
      stratified random sample of Black Hispanic female patients from the Surveillance
      Epidemiology and End Results (SEER) database to derive the statistical
      probability models. We used three common model building criteria which include
      Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and
      Deviance Information Criteria (DIC) to measure the goodness of fit tests and it
      was found that Black Hispanic female patients survival data better fit the
      exponentiated exponential probability model. A novel Bayesian method was used to
      derive the posterior density function for the model parameters as well as to
      derive the predictive inference for future response. We specifically focused on
      Black Hispanic race. Markov Chain Monte Carlo (MCMC) method was used for
      obtaining the summary results of posterior parameters. Additionally, we reported
      predictive intervals for future survival times. These findings would be of great
      significance in treatment planning and healthcare resource allocation. 

PMID- 24678274
TI  - Low-bit rate feedback strategies for iterative IA-precoded MIMO-OFDM-based
      systems.
AB  - Interference alignment (IA) is a promising technique that allows high-capacity
      gains in interference channels, but which requires the knowledge of the channel
      state information (CSI) for all the system links. We design low-complexity and
      low-bit rate feedback strategies where a quantized version of some CSI parameters
      is fed back from the user terminal (UT) to the base station (BS), which shares it
      with the other BSs through a limited-capacity backhaul network. This information
      is then used by BSs to perform the overall IA design. With the proposed
      strategies, we only need to send part of the CSI information, and this can even
      be sent only once for a set of data blocks transmitted over time-varying
      channels. These strategies are applied to iterative MMSE-based IA techniques for
      the downlink of broadband wireless OFDM systems with limited feedback. A new
      robust iterative IA technique, where channel quantization errors are taken into
      account in IA design, is also proposed and evaluated. With our proposed
      strategies, we need a small number of quantization bits to transmit and share the
      CSI, when comparing with the techniques used in previous works, while allowing
      performance close to the one obtained with perfect channel knowledge. 

PMID- 24678275
TI  - A study of frontier and semifrontier in intuitionistic fuzzy topological spaces.
AB  - Notions of frontier and semifrontier in intuitionistic fuzzy topology have been
      studied and several of their properties, characterizations, and examples
      established. Many counter-examples have been presented to point divergences
      between the IF topology and its classical form. The paper also presents an open
      problem and one of its weaker forms. 

PMID- 24678276
TI  - Some new traveling wave exact solutions of the (2+1)-dimensional Boiti-Leon
      Pempinelli equations.
AB  - We employ the complex method to obtain all meromorphic exact solutions of complex
      (2+1)-dimensional Boiti-Leon-Pempinelli equations (BLP system of equations). The
      idea introduced in this paper can be applied to other nonlinear evolution
      equations. Our results show that all rational and simply periodic traveling wave
      exact solutions of the equations (BLP) are solitary wave solutions, the complex
      method is simpler than other methods, and there exist some rational solutions
      ur,2 (z) and simply periodic solutions us,2-6(z) which are not only new but also
      not degenerated successively by the elliptic function solutions. We believe that
      this method should play an important role for finding exact solutions in the
      mathematical physics. For these new traveling wave solutions, we give some
      computer simulations to illustrate our main results.

PMID- 24678277
TI  - Integration and analysis of neighbor discovery and link quality estimation in
      wireless sensor networks.
AB  - Network connectivity and link quality information are the fundamental
      requirements of wireless sensor network protocols to perform their desired
      functionality. Most of the existing discovery protocols have only focused on the
      neighbor discovery problem, while a few number of them provide an integrated
      neighbor search and link estimation. As these protocols require a careful
      parameter adjustment before network deployment, they cannot provide scalable and
      accurate network initialization in large-scale dense wireless sensor networks
      with random topology. Furthermore, performance of these protocols has not
      entirely been evaluated yet. In this paper, we perform a comprehensive simulation
      study on the efficiency of employing adaptive protocols compared to the existing
      nonadaptive protocols for initializing sensor networks with random topology. In
      this regard, we propose adaptive network initialization protocols which integrate
      the initial neighbor discovery with link quality estimation process to initialize
      large-scale dense wireless sensor networks without requiring any parameter
      adjustment before network deployment. To the best of our knowledge, this work is
      the first attempt to provide a detailed simulation study on the performance of
      integrated neighbor discovery and link quality estimation protocols for
      initializing sensor networks. This study can help system designers to determine
      the most appropriate approach for different applications. 

PMID- 24678278
TI  - Spectral characterization and 3D molecular modeling studies of metal complexes
      involving the O, N-donor environment of quinazoline-4(3H)-one Schiff base and
      their biological studies.
AB  - A simple condensation of 3-amino-2-methylquinazoline-4-one with 2-hydroxy-1
      naphthaldehyde produced new tridentate ONO donor Schiff base ligand with
      efficient yield. The structural characterization of ligand and its Cu(II),
      Ni(II), Co(II), Mn(II), Zn(II), and Cd(II) complexes were achieved by the aid of
      elemental analysis, spectral characterization such as (UV-visible, IR, NMR, mass,
      and ESR), and magnetic data. The analytical and spectroscopic studies suggest the
      octahedral geometries of Cu(II), Co(II), Ni(II) and Mn(II) complexes and
      tetrahedral geometry of Zn(II) and Cd(II) complexes with the tridentate ONO
      Schiff base ligand. Furthermore, the conclusions drawn from these studies afford
      further support to the mode of bonding discussed on the basis of their 3D
      molecular modeling studies by considering different bond lengths, bond angles,
      and bond distance. The ligand and its metal complexes evaluated for their
      antimicrobial activity against Staphylococcus aureus (MTCC number 7443), Bacillus
      subtilis (MTCC number 9878), Escherichia coli (MTCC number 1698), Aspergillus
      niger (MTCC number 281), and Aspergillus flavus (MTCC number 277). The MIC of
      these compounds was found to be most active at 10 MU g/mL concentration in
      inhibiting the growth of the tested organisms. The DNA cleavage activity of all
      the complexes was studied by gel electrophoresis method.

PMID- 24678279
TI  - Functional characterization of sesquiterpene synthase from Polygonum minus.
AB  - Polygonum minus is an aromatic plant, which contains high abundance of
      terpenoids, especially the sesquiterpenes C15H24. Sesquiterpenes were believed to
      contribute to the many useful biological properties in plants. This study aimed
      to functionally characterize a full length sesquiterpene synthase gene from P.
      minus. P. minus sesquiterpene synthase (PmSTS) has a complete open reading frame
      (ORF) of 1689 base pairs encoding a 562 amino acid protein. Similar to other
      sesquiterpene synthases, PmSTS has two large domains: the N-terminal domain and
      the C-terminal metal-binding domain. It also consists of three conserved motifs:
      the DDXXD, NSE/DTE, and RXR. A three-dimensional protein model for PmSTS built
      clearly distinguished the two main domains, where conserved motifs were
      highlighted. We also constructed a phylogenetic tree, which showed that PmSTS
      belongs to the angiosperm sesquiterpene synthase subfamily Tps-a. To examine the
      function of PmSTS, we expressed this gene in Arabidopsis thaliana. Two transgenic
      lines, designated as OE3 and OE7, were further characterized, both molecularly
      and functionally. The transgenic plants demonstrated smaller basal rosette
      leaves, shorter and fewer flowering stems, and fewer seeds compared to wild type
      plants. Gas chromatography-mass spectrometry analysis of the transgenic plants
      showed that PmSTS was responsible for the production of beta -sesquiphellandrene.

PMID- 24678281
TI  - Empirical mode decomposition and neural networks on FPGA for fault diagnosis in
      induction motors.
AB  - Nowadays, many industrial applications require online systems that combine
      several processing techniques in order to offer solutions to complex problems as
      the case of detection and classification of multiple faults in induction motors.
      In this work, a novel digital structure to implement the empirical mode
      decomposition (EMD) for processing nonstationary and nonlinear signals using the
      full spline-cubic function is presented; besides, it is combined with an adaptive
      linear network (ADALINE)-based frequency estimator and a feed forward neural
      network (FFNN)-based classifier to provide an intelligent methodology for the
      automatic diagnosis during the startup transient of motor faults such as: one and
      two broken rotor bars, bearing defects, and unbalance. Moreover, the overall
      methodology implementation into a field-programmable gate array (FPGA) allows an
      online and real-time operation, thanks to its parallelism and high-performance
      capabilities as a system-on-a-chip (SoC) solution. The detection and
      classification results show the effectiveness of the proposed fused techniques;
      besides, the high precision and minimum resource usage of the developed digital
      structures make them a suitable and low-cost solution for this and many other
      industrial applications. 

PMID- 24678280
TI  - Investigation of the effects of curcumin on serum cytokines in obese individuals:
      a randomized controlled trial.
AB  - BACKGROUND: Obesity is a disorder often accompanied by a heightened state of
      systemic inflammation and immunoactivation. The present randomized crossover
      trial aimed to investigate the efficacy of curcumin, a bioactive polyphenol with
      established anti-inflammatory and immunomodulatory effects, on the serum levels
      of a panel of cytokines and mediators in obese individuals. METHODS: Thirty obese
      individuals were randomized to receive curcumin at a daily dose of 1 g or a
      matched placebo for 4 weeks. Following a 2-week wash-out period, each group was
      assigned to the alternate treatment regimen for another 4 weeks. Serum samples
      were collected at the start and end of each study period. Serum levels of IL
      1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFNgamma, EGF, MCP-1, and
      TNF alpha were measured using a multiplex Biochip Array Technology based method.
      RESULTS: Mean serum IL-1beta (P = 0.042), IL-4 (P = 0.008), and VEGF (P = 0.01)
      were found to be significantly reduced by curcumin therapy. In contrast, no
      significant difference was observed in the concentrations of IL-2, IL-6, IL-8, IL
      10, IFNgamma, EGF, and MCP-1. CONCLUSIONS: The findings of the present trial
      suggested that curcumin may exert immunomodulatory effects via altering the
      circulating concentrations of IL-1beta, IL-4, and VEGF.

PMID- 24678282
TI  - Identification of family specific fingerprints in beta-lactamase families.
AB  - Beta-lactamases are a superfamily of enzymes which degrade the beta-lactam class
      of antibiotics. They are produced endogenously by the bacterial cells, which when
      exposed to the beta-lactam class of antibiotics inactivate them by cleaving the
      beta-lactam ring. Based on the presence or absence of metallic ligand, beta
      lactamases have been divided into two broad functional classes. beta-Lactamases
      are a constitutively evolving and expanding superfamily of enzymes, which could
      be further subdivided on the basis of presence/absence of conserved motifs. In
      the present study we have used the MEME/MAST suit to identify the patterns/motifs
      which are specific to a particular family or subfamily of beta-lactamases. The
      family specific patterns/motifs can be also useful in recognizing and assigning
      newly discovered beta-lactamases to one or the other family or subfamily. Cross
      validation showed that the proposed method is highly sensitive and specific. We
      have also designed a webserver, LactFP, for this purpose.

PMID- 24678283
TI  - Characterizing HIV medication adherence for virologic success among individuals
      living with HIV/AIDS: Experience with the CNS HIV Antiretroviral Therapy Effects
      Research (CHARTER) cohort.
AB  - Antiretroviral therapy (ART) has changed HIV related illness from terminal to
      chronic by suppressing viral load which results in immunologic and clinical
      improvement. Success with ART is dependent on optimal adherence, commonly
      categorized as >95%. As medication type, class and frequency of use continue to
      evolve, we assessed adherence levels related to viral suppression. Using a cross
      sectional analysis with secondary data (n = 381) from an ongoing multi-site study
      on impact of ART on the Central Nervous System (CNS), we compared self-reported
      adherence rates with biological outcomes of HIV-RNA copies/ml, and CD4 cell/mm3.
      Adherence to ART measures included taking all prescribed medication as directed
      on schedule and following dietary restrictions. While depression was a barrier to
      adherence, undetectable viral suppression was achieved at pill adherence
      percentages lower than 95%. Practice, research and policy implications are
      discussed in the context of patient-, provider-, and system-level factors
      influencing adherence to ART.

PMID- 24678284
TI  - A Power-Efficient Wireless Capacitor Charging System Through an Inductive Link.
AB  - A power-efficient wireless capacitor charging system for inductively powered
      applications has been presented. A bank of capacitors can be directly charged
      from an ac source by generating a current through a series charge injection
      capacitor and a capacitor charger circuit. The fixed charging current reduces
      energy loss in switches, while maximizing the charging efficiency. An adaptive
      capacitor tuner compensates for the resonant capacitance variations during
      charging to keep the amplitude of the ac input voltage at its peak. We have
      fabricated the capacitor charging system prototype in a 0.35-MUm 4-metal 2-poly
      standard CMOS process in 2.1 mm2 of chip area. It can charge four pairs of
      capacitors sequentially. While receiving 2.7-V peak ac input through a 2-MHz
      inductive link, the capacitor charging system can charge each pair of 1 MUF
      capacitors up to +/-2 V in 420 MUs, achieving a high measured charging efficiency
      of 82%.

PMID- 24678285
TI  - Revising the Representation of Fatty Acid, Glycerolipid, and Glycerophospholipid
      Metabolism in the Consensus Model of Yeast Metabolism.
AB  - Genome-scale metabolic models are built using information from an organism's
      annotated genome and, correspondingly, information on reactions catalyzed by the
      set of metabolic enzymes encoded by the genome. These models have been
      successfully applied to guide metabolic engineering to increase production of
      metabolites of industrial interest. Congruity between simulated and experimental
      metabolic behavior is influenced by the accuracy of the representation of the
      metabolic network in the model. In the interest of applying the consensus model
      of Saccharomyces cerevisiae metabolism for increased productivity of
      triglycerides, we manually evaluated the representation of fatty acid,
      glycerophospholipid, and glycerolipid metabolism in the consensus model (Yeast
      v6.0). These areas of metabolism were chosen due to their tightly interconnected
      nature to triglyceride synthesis. Manual curation was facilitated by custom
      MATLAB functions that return information contained in the model for reactions
      associated with genes and metabolites within the stated areas of metabolism.
      Through manual curation, we have identified inconsistencies between information
      contained in the model and literature knowledge. These inconsistencies include
      incorrect gene-reaction associations, improper definition of substrates/products
      in reactions, inappropriate assignments of reaction directionality, nonfunctional
      beta-oxidation pathways, and missing reactions relevant to the synthesis and
      degradation of triglycerides. Suggestions to amend these inconsistencies in the
      Yeast v6.0 model can be implemented through a MATLAB script provided in
      theSupplementary Materials, Supplementary Data S1(Supplementary Data are
      available online at www.liebertpub.com/ind).

PMID- 24678286
TI  - Central Hypoventilation Syndromes.

PMID- 24678288
TI  - Hormonal response to L-arginine supplementation in physically active individuals.
AB  - BACKGROUND: Nutritional supplements based on the amino acid L-arginine have been
      hypothesized to improve exercise performance by increasing levels of insulin and
      growth hormone (GH). Changes of these parameters in response to L-arginine
      supplementation may clarify the mechanisms underlying its putative physiological
      effects on physical performance. OBJECTIVE: The aim of the study was to evaluate
      the effect of L-arginine supplementation on serum insulin, GH, Growth Factor
      Insulin-like (IGF-1), and cortisol in response to exercise. Exercise performance
      was also evaluated. DESIGN: Fifteen trained runners were divided into groups
      supplemented with 6 g of L-arginine (ARG) or placebo (PLA). Blood samples were
      collected before supplementation (T0), immediately after the first exercise
      session (T1), after the second exercise session (T2), and after 20 min of rest
      (T3). The exercise consisted of two bouts of 5 km time-trial running test.
      RESULTS: There was a significant increase in serum GH (T0: 3.28+/-0.95 vs. 3.21+/
      0.5 ng/mL; T1: 4.35+/-0.23 vs. 4.17+/-0.13 ng/mL; T2: 4.22+/-0.25 vs. 4.17+/-0.09
      ng/mL; T3: 4.14+/-0.29 vs. 4.13+/-0.18 ng/mL) and cortisol (T0: 198.71+/-53.77
      vs. 207.57+/-69.51 nmol/L; T1: 458.16+/-116.12 vs. 433.26+/-101.77 nmol/L; T2:
      454.61+/-125.21 vs. 431.88+/-74.82 nmol/L; T3: 311.14+/-102.91 vs. 362.26+/
      110.42 nmol/L) after T1, T2, and T3, with no significant difference between the
      ARG and PLA groups, respectively. There was also no significant difference
      observed in the variables of IGF-1, insulin, and total running time between the
      ARG and PLA groups. CONCLUSIONS: The supplementation of L-arginine did not appear
      to stimulate the production of insulin, GH, and IGF-1 and, thus, provided no
      benefit in hormonal response or exercise performance in trained runners.

PMID- 24678287
TI  - Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons.
AB  - Phytochemicals are a rich source of anticancer drugs and chemopreventive agents.
      Several of these chemicals appear to exert at least some of their effects through
      interactions with topoisomerase II, an essential enzyme that regulates DNA
      supercoiling and removes knots and tangles from the genome. Topoisomerase II
      active phytochemicals function by stabilizing covalent protein-cleaved DNA
      complexes that are intermediates in the catalytic cycle of the enzyme. As a
      result, these compounds convert topoisomerase II to a cellular toxin that
      fragments the genome. Because of their mode of action, they are referred to as
      topoisomerase II poisons as opposed to catalytic inhibitors. The first sections
      of this article discuss DNA topology, the catalytic cycle of topoisomerase II,
      and the two mechanisms (interfacial vs. covalent) by which different classes of
      topoisomerase II poisons alter enzyme activity. Subsequent sections discuss the
      effects of several phytochemicals on the type II enzyme, including demethyl
      epipodophyllotoxins (semisynthetic anticancer drugs) as well as flavones,
      flavonols, isoflavones, catechins, isothiocyanates, and curcumin (dietary
      chemopreventive agents). Finally, the leukemogenic potential of topoisomerase II
      targeted phytochemicals is described.

PMID- 24678290
TI  - Heritable and inducible gene knockdown in astrocytes or neurons in vivo by a
      combined lentiviral and RNAi approach.
AB  - Gene knockout by homologous recombination is a popular method to study gene
      functions in the mouse in vivo. However, its lack of temporal control has limited
      the interpretation of knockout studies because the complete elimination of a gene
      product often alters developmental processes, and can induce severe malformations
      or lethality. Conditional gene knockdown has emerged as a compelling alternative
      to gene knockout, an approach well-established in vitro but that remains
      challenging in vivo, especially in the adult brain. Here, we report a method for
      conditional and cell-specific gene knockdown in the mouse brain in vivo that
      combines Cre-mediated RNA interference (RNAi) with classical and lentivirus
      mediated transgenesis. The method is based on the inducible expression of a
      silencing short hairpin RNA (shRNA) introduced in mice by lentivirus-mediated
      transgenesis, and on its activation by excision of a floxed stop EGFP reporter
      with an inducible Cre recombinase expressed in astrocytes or in neurons. This
      dual system should be of broad utility for comparative studies of gene functions
      in these two cell types in vivo. 

PMID- 24678289
TI  - The amygdalo-motor pathways and the control of facial expressions.
AB  - Facial expressions reflect decisions about the perceived meaning of social
      stimuli and the expected socio-emotional outcome of responding (or not) with a
      reciprocating expression. The decision to produce a facial expression emerges
      from the joint activity of a network of structures that include the amygdala and
      multiple, interconnected cortical and subcortical motor areas. Reciprocal
      transformations between these sensory and motor signals give rise to distinct
      brain states that promote, or impede the production of facial expressions. The
      muscles of the upper and lower face are controlled by anatomically distinct motor
      areas. Facial expressions engage to a different extent the lower and upper face
      and thus require distinct patterns of neural activity distributed across multiple
      facial motor areas in ventrolateral frontal cortex, the supplementary motor area,
      and two areas in the midcingulate cortex. The distributed nature of the decision
      manifests in the joint activation of multiple motor areas that initiate the
      production of facial expression. Concomitantly multiple areas, including the
      amygdala, monitor ongoing overt behaviors (the expression itself) and the covert,
      autonomic responses that accompany emotional expressions. As the production of
      facial expressions is brought into the framework of formal decision making, an
      important challenge will be to incorporate autonomic and visceral states into
      decisions that govern the receiving-emitting cycle of social signals. 

PMID- 24678291
TI  - Excitability properties of single human motor axons: are all axons identical?

PMID- 24678292
TI  - Is there evidence for neurodegenerative change following traumatic brain injury
      in children and youth? A scoping review.
AB  - While generalized cerebral atrophy and neurodegenerative change following
      traumatic brain injury (TBI) is well recognized in adults, it remains
      comparatively understudied in the pediatric population, suggesting that research
      should address the potential for neurodegenerative change in children and youth
      following TBI. This focused review examines original research findings
      documenting evidence for neurodegenerative change following TBI of all severities
      in children and youth. Our relevant inclusion and exclusion criteria identified a
      total of 16 articles for review. Taken together, the studies reviewed suggest
      there is evidence for long-term neurodegenerative change following TBI in
      children and youth. In particular both cross-sectional and longitudinal studies
      revealed volume loss in selected brain regions including the hippocampus,
      amygdala, globus pallidus, thalamus, periventricular white matter, cerebellum,
      and brain stem as well as overall decreased whole brain volume and increased CSF
      and ventricular space. Diffusion Tensor Imaging (DTI) studies also report
      evidence for decreased cellular integrity, particularly in the corpus callosum.
      Sensitivity of the hippocampus and deep limbic structures in pediatric
      populations are similar to findings in the adult literature and we consider the
      data supporting these changes as well as the need to investigate the possibility
      of neurodegenerative onset in childhood associated with mild traumatic brain
      injury (mTBI). 

PMID- 24678294
TI  - Loss of form vision impairs spatial imagery.
AB  - Previous studies have reported inconsistent results when comparing spatial
      imagery performance in the blind and the sighted, with some, but not all, studies
      demonstrating deficits in the blind. Here, we investigated the effect of visual
      status and individual preferences ("cognitive style") on performance of a spatial
      imagery task. Participants with blindness resulting in the loss of form vision at
      or after age 6, and age- and gender-matched sighted participants, performed a
      spatial imagery task requiring memorization of a 4 * 4 lettered matrix and
      subsequent mental construction of shapes within the matrix from four-letter
      auditory cues. They also completed the Santa Barbara Sense of Direction Scale
      (SBSoDS) and a self-evaluation of cognitive style. The sighted participants also
      completed the Object-Spatial Imagery and Verbal Questionnaire (OSIVQ). Visual
      status affected performance on the spatial imagery task: the blind performed
      significantly worse than the sighted, independently of the age at which form
      vision was completely lost. Visual status did not affect the distribution of
      preferences based on self-reported cognitive style. Across all participants, self
      reported verbalizer scores were significantly negatively correlated with accuracy
      on the spatial imagery task. There was a positive correlation between the SBSoDS
      score and accuracy on the spatial imagery task, across all participants,
      indicating that a better sense of direction is related to a more proficient
      spatial representation and that the imagery task indexes ecologically relevant
      spatial abilities. Moreover, the older the participants were, the worse their
      performance was, indicating a detrimental effect of age on spatial imagery
      performance. Thus, spatial skills represent an important target for
      rehabilitative approaches to visual impairment, and individual differences, which
      can modulate performance, should be taken into account in such approaches. 

PMID- 24678293
TI  - Neuroimaging correlates of handwriting quality as children learn to read and
      write.
AB  - Reading and writing are related but separable processes that are crucial skills
      to possess in modern society. The neurobiological basis of reading acquisition
      and development, which critically depends on phonological processing, and to a
      lesser degree, beginning writing as it relates to letter perception, are
      increasingly being understood. Yet direct relationships between writing and
      reading development, in particular, with phonological processing is not well
      understood. The main goal of the current preliminary study was to examine
      individual differences in neurofunctional and neuroanatomical patterns associated
      with handwriting in beginning writers/readers. In 46 5-6 year-old beginning
      readers/writers, ratings of handwriting quality, were rank-ordered from best to
      worst and correlated with brain activation patterns during a phonological task
      using functional MRI, and with regional gray matter volume from structural T1
      MRI. Results showed that better handwriting was associated negatively with
      activation and positively with gray matter volume in an overlapping region of the
      pars triangularis of right inferior frontal gyrus. This region, in particular in
      the left hemisphere in adults and more bilaterally in young children, is known to
      be important for decoding, phonological processing, and subvocal rehearsal. We
      interpret the dissociation in the directionality of the association in functional
      activation and morphometric properties in the right inferior frontal gyrus in
      terms of neural efficiency, and suggest future studies that interrogate the
      relationship between the neural mechanisms underlying reading and writing
      development. 

PMID- 24678295
TI  - Assessing dynamics, spatial scale, and uncertainty in task-related brain network
      analyses.
AB  - The brain is a complex network of interconnected elements, whose interactions
      evolve dynamically in time to cooperatively perform specific functions. A common
      technique to probe these interactions involves multi-sensor recordings of brain
      activity during a repeated task. Many techniques exist to characterize the
      resulting task-related activity, including establishing functional networks,
      which represent the statistical associations between brain areas. Although
      functional network inference is commonly employed to analyze neural time series
      data, techniques to assess the uncertainty-both in the functional network edges
      and the corresponding aggregate measures of network topology-are lacking. To
      address this, we describe a statistically principled approach for computing
      uncertainty in functional networks and aggregate network measures in task-related
      data. The approach is based on a resampling procedure that utilizes the trial
      structure common in experimental recordings. We show in simulations that this
      approach successfully identifies functional networks and associated measures of
      confidence emergent during a task in a variety of scenarios, including
      dynamically evolving networks. In addition, we describe a principled technique
      for establishing functional networks based on predetermined regions of interest
      using canonical correlation. Doing so provides additional robustness to the
      functional network inference. Finally, we illustrate the use of these methods on
      example invasive brain voltage recordings collected during an overt speech task.
      The general strategy described here-appropriate for static and dynamic network
      inference and different statistical measures of coupling-permits the evaluation
      of confidence in network measures in a variety of settings common to
      neuroscience. 

PMID- 24678296
TI  - Effects of antidromic and orthodromic activation of STN afferent axons during DBS
      in Parkinson's disease: a simulation study.
AB  - Recent studies suggest that subthalamic nucleus (STN)-Deep Brain Stimulation
      (DBS) may exert at least part of its therapeutic effect through the antidromic
      suppression of pathological oscillations in the cortex in 6-OHDA treated rats and
      in parkinsonian patients. STN-DBS may also activate STN neurons by initiating
      action potential propagation in the orthodromic direction, similarly resulting in
      suppression of pathological oscillations in the STN. While experimental studies
      have provided strong evidence in support of antidromic stimulation of cortical
      neurons, it is difficult to separate relative contributions of antidromic and
      orthodromic effects of STN-DBS. The aim of this computational study was to
      examine the effects of antidromic and orthodromic activation on neural firing
      patterns and beta-band (13-30 Hz) oscillations in the STN and cortex during DBS
      of STN afferent axons projecting from the cortex. High frequency antidromic
      stimulation alone effectively suppressed simulated beta activity in both the
      cortex and STN-globus pallidus externa (GPe) network. High frequency orthodromic
      stimulation similarly suppressed beta activity within the STN and GPe through the
      direct stimulation of STN neurons driven by DBS at the same frequency as the
      stimulus. The combined effect of both antidromic and orthodromic stimulation
      modulated cortical activity antidromically while simultaneously orthodromically
      driving STN neurons. While high frequency DBS reduced STN beta-band power, low
      frequency stimulation resulted in resonant effects, increasing beta-band
      activity, consistent with previous experimental observations. The simulation
      results indicate effective suppression of simulated oscillatory activity through
      both antidromic stimulation of cortical neurons and direct orthodromic
      stimulation of STN neurons. The results of the study agree with experimental
      recordings of STN and cortical neurons in rats and support the therapeutic
      potential of stimulation of cortical neurons. 

PMID- 24678297
TI  - QSpike tools: a generic framework for parallel batch preprocessing of
      extracellular neuronal signals recorded by substrate microelectrode arrays.
AB  - Micro-Electrode Arrays (MEAs) have emerged as a mature technique to investigate
      brain (dys)functions in vivo and in in vitro animal models. Often referred to as
      "smart" Petri dishes, MEAs have demonstrated a great potential particularly for
      medium-throughput studies in vitro, both in academic and pharmaceutical
      industrial contexts. Enabling rapid comparison of ionic/pharmacological/genetic
      manipulations with control conditions, MEAs are employed to screen compounds by
      monitoring non-invasively the spontaneous and evoked neuronal electrical activity
      in longitudinal studies, with relatively inexpensive equipment. However, in order
      to acquire sufficient statistical significance, recordings last up to tens of
      minutes and generate large amount of raw data (e.g., 60 channels/MEA, 16 bits A/D
      conversion, 20 kHz sampling rate: approximately 8 GB/MEA,h uncompressed). Thus,
      when the experimental conditions to be tested are numerous, the availability of
      fast, standardized, and automated signal preprocessing becomes pivotal for any
      subsequent analysis and data archiving. To this aim, we developed an in-house
      cloud-computing system, named QSpike Tools, where CPU-intensive operations,
      required for preprocessing of each recorded channel (e.g., filtering, multi-unit
      activity detection, spike-sorting, etc.), are decomposed and batch-queued to a
      multi-core architecture or to a computers cluster. With the commercial
      availability of new and inexpensive high-density MEAs, we believe that
      disseminating QSpike Tools might facilitate its wide adoption and customization,
      and inspire the creation of community-supported cloud-computing facilities for
      MEAs users. 

PMID- 24678298
TI  - Anodal tDCS during face-name associations memory training in Alzheimer's
      patients.
AB  - OBJECTIVE: Given the limited effectiveness of pharmacological treatments, non
      pharmacological interventions to treat Alzheimer's disease (AD) have gained
      attention in recent years. The aim of the present study is to investigate the
      effects of anodal tDCS (AtDCS) combined with memory training on face-name
      associations in an AD patient sample. METHODS: Thirty six AD patients were
      randomly assigned to one of three study groups: Group 1, AtDCS plus
      individualized computerized memory training; Group 2, placebo tDCS plus
      individualized computerized memory training; Group 3, AtDCS plus motor training.
      RESULTS: A general improvement in performance was observed after 2 weeks of
      memory training. Both the anodal tDCS plus individualized computerized memory
      training and the placebo tDCS plus individualized computerized memory training
      groups had significantly improved performances at 2 weeks compared with the AtDCS
      plus motor training group. CONCLUSION: Our findings suggest a beneficial effect
      of individualized memory rehabilitation in AD patients.

PMID- 24678299
TI  - Biomarker-based diagnosis of mild cognitive impairment due to Alzheimer's
      disease: how and what to tell. A kickstart to an ethical discussion.
AB  - New criteria for the diagnosis of Alzheimer's disease (AD) based on biomarker
      results have recently been developed and are currently undergoing extensive
      validation. The next few years may represent a time window where the diagnostic
      validity of biomarkers will be studied in highly specialized research settings.
      Biomarkers results will be used to direct clinical diagnosis and, whenever
      appropriate, therapy and management. This piece aims to stimulate discussion by
      identifying the ethical challenges involved in the use of biomarkers to make a
      diagnosis of mild cognitive impairment due to AD and disclose it to patients. At
      the individual level, these challenges are related to (i) the ethical
      appropriateness of implementing an ecological diagnostic research protocol, (ii)
      the related informed consent process, and (iii) the diagnostic disclosure. We
      justify the ethical legitimacy of implementing a research diagnostic protocol by
      referring to the respect of patients' subjectivity and autonomy, and we suggest
      guidelines for informed consent development and diagnostic disclosure. All of the
      above points are discussed in light of the unique features of AD, currently
      scanty treatment options, and knowledge and uncertainties regarding the
      diagnostic value of biomarkers. 

PMID- 24678300
TI  - Ginseng ginsenoside pharmacology in the nervous system: involvement in the
      regulation of ion channels and receptors.
AB  - Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional
      medicines and is thought to be a tonic. It has been claimed that ginseng may
      improve vitality and health. Recent studies have advanced ginseng pharmacology
      and shown that ginseng has various pharmacological effects in the nervous system.
      Ginsenosides, steroid glycosides extracted from ginseng, were one of the first
      class of biologically active plant glycosides identified. The diverse
      pharmacological effects of ginsenosides have been investigated through the
      regulation of various types of ion channels and receptors in neuronal cells and
      heterologous expression systems. Ginsenoside Rg3 regulates voltage-gated ion
      channels such as Ca(2+), K(+), and Na(+) channels, and ligand-gated ion channels
      such as GABAA, 5-HT3, nicotinic acetylcholine, and N-methyl-D-aspartate (NMDA)
      receptors through interactions with various sites including channel blocker
      binding sites, toxin-binding sites, channel gating regions, and allosteric
      channel regulator binding sites when the respective ion channels or receptors are
      stimulated with depolarization or ligand treatment. Treatment with ginsenoside
      Rg3 has been found to stabilize excitable cells by blocking influxes of cations
      such as Ca(2+) and Na(+), or by enhancing Cl(-) influx. The aim of this review is
      to present recent findings on the pharmacological functions of the ginsenosides
      through the interactions with ion channels and receptors. This review will detail
      the pharmacological applications of ginsenosides as neuroprotective drugs that
      target ion channels and ligand-gated ion channels. 

PMID- 24678301
TI  - Effect of acute resistance exercise on carotid artery stiffness and cerebral
      blood flow pulsatility.
AB  - Arterial stiffness is associated with cerebral flow pulsatility. Arterial
      stiffness increases following acute resistance exercise (RE). Whether this acute
      RE-induced vascular stiffening affects cerebral pulsatility remains unknown.
      PURPOSE: To investigate the effects of acute RE on common carotid artery (CCA)
      stiffness and cerebral blood flow velocity (CBFv) pulsatility. METHODS: Eighteen
      healthy men (22 +/- 1 yr; 23.7 +/- 0.5 kg.m(-2)) underwent acute RE (5 sets, 5-RM
      bench press, 5 sets 10-RM bicep curls with 90 s rest intervals) or a time control
      condition (seated rest) in a randomized order. CCA stiffness (beta-stiffness,
      Elastic Modulus (Ep)) and hemodynamics (pulsatility index, forward wave
      intensity, and reflected wave intensity) were assessed using a combination of
      Doppler ultrasound, wave intensity analysis and applanation tonometry at baseline
      and 3 times post-RE. CBFv pulsatility index was measured with transcranial
      Doppler at the middle cerebral artery (MCA). RESULTS: CCA beta-stiffness, Ep and
      CCA pulse pressure significantly increased post-RE and remained elevated
      throughout post-testing (p < 0.05). No changes in MCA or CCA pulsatility index
      were observed (p > 0.05). There were significant increases in forward wave
      intensity post-RE (p < 0.05) but not reflected wave intensity (p > 0.05).
      CONCLUSION: Although acute RE increases CCA stiffness and pressure pulsatility,
      it does not affect CCA or MCA flow pulsatility. Increases in pressure pulsatility
      may be due to increased forward wave intensity and not pressure from wave
      reflections.

PMID- 24678303
TI  - Skin sympathetic nerve activity in humans during exposure to emotionally-charged
      images: sex differences.
AB  - While it is known that anxiety or emotional arousal affects skin sympathetic
      nerve activity (SSNA), the galvanic skin response (GSR) is the most widely used
      parameter to infer increases in SSNA during stress or emotional studies. We
      recently showed that SSNA provides a more sensitive measure of emotional state
      than effector-organ responses. The aim of the present study was to assess whether
      there are gender differences in the responses of SSNA and other physiological
      parameters such as blood pressure, heart rate, skin blood flow and sweat release,
      while subjects viewed neutral or emotionally-charged images from the
      International Affective Picture System (IAPS). Changes in SSNA were assessed
      using microneurography in 20 subjects (10 male and 10 female). Blocks of
      positively-charged (erotica) or negatively-charge images (mutilation) were
      presented in a quasi-random fashion, following a block of neutral images, with
      each block containing 15 images and lasting 2 min. Images of both erotica and
      mutilation caused significant increases in SSNA, with increases being greater for
      males viewing erotica and greater for females viewing mutilation. The increases
      in SSNA were often coupled with sweat release and cutaneous vasoconstriction;
      however, these markers were not significantly different than those produced by
      viewing neutral images and were not always consistent with the SSNA increases. We
      conclude that SSNA increases with both positively-charged and negatively-charged
      emotional images, yet sex differences are present. 

PMID- 24678302
TI  - Structural alterations of skeletal muscle in copd.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory disease
      associated with a systemic inflammatory response. Peripheral muscle dysfunction
      has been well characterized in individuals with COPD and results from a complex
      interaction between systemic and local factors. OBJECTIVE: In this narrative
      review, we will describe muscle wasting in people with COPD, the associated
      structural changes, muscle regenerative capacity and possible mechanisms for
      muscle wasting. We will also discuss how structural changes relate to impaired
      muscle function and mobility in people with COPD. Key Observations: Approximately
      30-40% of individuals with COPD experience muscle mass depletion. Furthermore,
      muscle atrophy is a predictor of physical function and mortality in this
      population. Associated structural changes include a decreased proportion and size
      of type-I fibers, reduced oxidative capacity and mitochondrial density mainly in
      the quadriceps. Observations related to impaired muscle regenerative capacity in
      individuals with COPD include a lower proportion of central nuclei in the
      presence or absence of muscle atrophy and decreased maximal telomere length,
      which has been correlated with reduced muscle cross-sectional area. Potential
      mechanisms for muscle wasting in COPD may include excessive production of
      reactive oxygen species (ROS), altered amino acid metabolism and lower expression
      of peroxisome proliferator-activated receptors-gamma-coactivator 1-alpha mRNA.
      Despite a moderate relationship between muscle atrophy and function, impairments
      in oxidative metabolism only seems weakly related to muscle function. CONCLUSION:
      This review article demonstrates the cellular modifications in the peripheral
      muscle of people with COPD and describes the evidence of its relationship to
      muscle function. Future research will focus on rehabilitation strategies to
      improve muscle wasting and maximize function.

PMID- 24678304
TI  - Perceptual chunking and its effect on memory in speech processing: ERP and
      behavioral evidence.
AB  - We examined how perceptual chunks of varying size in utterances can influence
      immediate memory of heard items (monosyllabic words). Using behavioral measures
      and event-related potentials (N400) we evaluated the quality of the memory trace
      for targets taken from perceived temporal groups (TGs) of three and four items.
      Variations in the amplitude of the N400 showed a better memory trace for items
      presented in TGs of three compared to those in groups of four. Analyses of
      behavioral responses along with P300 components also revealed effects of chunk
      position in the utterance. This is the first study to measure the online effects
      of perceptual chunks on the memory trace of spoken items. Taken together, the
      N400 and P300 responses demonstrate that the perceptual chunking of speech
      facilitates information buffering and a processing on a chunk-by-chunk basis. 

PMID- 24678305
TI  - Conceptual and empirical problems with game theoretic approaches to language
      evolution.
AB  - The importance of game theoretic models to evolutionary theory has been in
      formulating elegant equations that specify the strategies to be played and the
      conditions to be satisfied for particular traits to evolve. These models, in
      conjunction with experimental tests of their predictions, have successfully
      described and explained the costs and benefits of varying strategies and the
      dynamics for establishing equilibria in a number of evolutionary scenarios,
      including especially cooperation, mating, and aggression. Over the past decade or
      so, game theory has been applied to model the evolution of language. In contrast
      to the aforementioned scenarios, however, we argue that these models are
      problematic due to conceptual confusions and empirical difficiences. In
      particular, these models conflate the comptutations and representations of our
      language faculty (mechanism) with its utility in communication (function); model
      languages as having different fitness functions for which there is no evidence;
      depend on assumptions for the starting state of the system, thereby begging the
      question of how these systems evolved; and to date, have generated no empirical
      studies at all. Game theoretic models of language evolution have therefore failed
      to advance how or why language evolved, or why it has the particular
      representations and computations that it does. We conclude with some brief
      suggestions for how this situation might be ameliorated, enabling this important
      theoretical tool to make substantive empirical contributions. 

PMID- 24678306
TI  - Construction and updating of a public events questionnaire for repeated measures
      longitudinal studies.
AB  - Impairments of retrospective memory and cases of retrograde amnesia are often
      seen in clinical settings. A measure of the proportion of memories retained over
      a specified time can be useful in clinical situations and public events
      questionnaires may be valuable in this respect. However, consistency of retention
      of public events memory has rarely been studied in the same participants. In
      addition, when used in a research context, public events questionnaires require
      updating to ensure questions are of equivalent age with respect to when the test
      is taken. This paper describes an approach to constructing and updating a Public
      Events Questionnaire (PEQ) for use with a sample that is recruited and followed
      up over a long time-period. Internal consistency, parallel-form reliability, test
      retest reliability, and secondary validity analyses were examined for three
      versions of the PEQ that were updated every 6 months. Versions 2 and 3 of the
      questionnaire were reliable across and within versions and for recall and
      recognition. Change over time was comparable across each version of the PEQ.
      These results show that PEQs can be regularly updated in a standardized fashion
      to allow use throughout studies with long recruitment periods. 

PMID- 24678307
TI  - Methods for Surgical Targeting of the STN in Early-Stage Parkinson's Disease.
AB  - Patients with Parkinson's disease (PD) experience progressive neurological
      decline, and future interventional therapies are thought to show most promise in
      early stages of the disease. There is much interest in therapies that target the
      subthalamic nucleus (STN) with surgical access. While locating STN in advanced
      disease patients (Hoehn-Yahr Stage III or IV) is well understood and routinely
      performed at many centers in the context of deep brain stimulation surgery, the
      ability to identify this nucleus in early-stage patients has not previously been
      explored in a sizeable cohort. We report surgical methods used to target the STN
      in 15 patients with early PD (Hoehn-Yahr Stage II), using a combination of image
      guided surgery, microelectrode recordings, and clinical responses to
      macrostimulation of the region surrounding the STN. Measures of electrophysiology
      (firing rates and root mean squared activity) have previously been found to be
      lower than in later-stage patients, however, the patterns of electrophysiology
      seen and dopamimetic macrostimulation effects are qualitatively similar to those
      seen in advanced stages. Our experience with surgical implantation of Parkinson's
      patients with minimal motor symptoms suggest that it remains possible to
      accurately target the STN in early-stage PD using traditional methods. 

PMID- 24678308
TI  - Pan-genome analyses identify lineage- and niche-specific markers of evolution and
      adaptation in Epsilonproteobacteria.
AB  - The rapidly increasing availability of complete bacterial genomes has created new
      opportunities for reconstructing bacterial evolution, but it has also highlighted
      the difficulty to fully understand the genomic and functional variations
      occurring among different lineages. Using the class Epsilonproteobacteria as a
      case study, we investigated the composition, flexibility, and function of its pan
      genomes. Models were constructed to extrapolate the expansion of pan-genomes at
      three different taxonomic levels. The results show that, for
      Epsilonproteobacteria the seemingly large genome variations among strains of the
      same species are less noticeable when compared with groups at higher taxonomic
      ranks, indicating that genome stability is imposed by the potential existence of
      taxonomic boundaries. The analyses of pan-genomes has also defined a set of
      universally conserved core genes, based on which a phylogenetic tree was
      constructed to confirm that thermophilic species from deep-sea hydrothermal vents
      represent the most ancient lineages of Epsilonproteobacteria. Moreover, by
      comparing the flexible genome of a chemoautotrophic deep-sea vent species to (1)
      genomes of species belonging to the same genus, but inhabiting different
      environments, and (2) genomes of other vent species, but belonging to different
      genera, we were able to delineate the relative importance of lineage-specific
      versus niche-specific genes. This result not only emphasizes the overall
      importance of phylogenetic proximity in shaping the variable part of the genome,
      but also highlights the adaptive functions of niche-specific genes. Overall, by
      modeling the expansion of pan-genomes and analyzing core and flexible genes, this
      study provides snapshots on how the complex processes of gene acquisition,
      conservation, and removal affect the evolution of different species, and
      contribute to the metabolic diversity and versatility of Epsilonproteobacteria. 

PMID- 24678309
TI  - PD-1(HIGH) Follicular CD4 T Helper Cell Subsets Residing in Lymph Node Germinal
      Centers Correlate with B Cell Maturation and IgG Production in Rhesus Macaques.
AB  - CD4+ T follicular helper (TFH) cells guide development and maturation of B cells
      and are crucial for effective antibody responses. Here we found rhesus macaque
      TFH cells, defined as CXCR5+CD4 T cells, contain two major populations: PD-1(INT)
      and PD-1(HIGH) cells. Of these, PD-1(HIGH)CD4+ T cells highly co-express ICOS but
      little CCR7, and reside in lymph node germinal centers (GCs), but not in blood.
      These cells secrete IL-21 and express transcriptional factor Bcl-6 at higher
      levels than CXCR5+PD-1(INT)CD4+ T cells. In addition, the frequency of PD
      1(HIGH)CD4+ T cells is low in lymph nodes of newborns, but increases with age.
      Levels of PD-1(HIGH)CD4+ T cells correlate with mature B cells in lymph nodes,
      and PD-1 blockade in PD-1(HIGH)CD4+ T and B cell co-cultures significantly
      inhibits IgG production. In summary, PD-1(HIGH)CD4+ T cells residing in GC
      represent a specific TFH subset that contributes to maturation of B cells and IgG
      production. 

PMID- 24678310
TI  - Differences in the composition of the human antibody repertoire by B cell subsets
      in the blood.
AB  - The vast initial diversity of the antibody repertoire is generated centrally by
      means of a complex series of V(D)J gene rearrangement events, variation in the
      site of gene segment joining, and TdT catalyzed N-region addition. Although the
      diversity is great, close inspection has revealed distinct and unique
      characteristics in the antibody repertoires expressed by different B cell
      developmental subsets. In order to illustrate our approach to repertoire
      analysis, we present an in-depth comparison of V(D)J gene usage, hydrophobicity,
      length, DH reading frame, and amino acid usage between heavy chain repertoires
      expressed by immature, transitional, mature, memory IgD(+), memory IgD(-), and
      plasmacytes isolated from the blood of a single individual. Our results support
      the view that in both human and mouse, the H chain repertoires expressed by
      individual, developmental B cell subsets appear to differ in sequence content.
      Sequencing of unsorted B cells from the blood is thus likely to yield an
      incomplete or compressed view of what is actually happening in the immune
      response of the individual. Our findings support the view that studies designed
      to correlate repertoire expression with diseases of immune function will likely
      require deep sequencing of B cells sorted by subset. 

PMID- 24678312
TI  - Immune privilege and the philosophy of immunology.

PMID- 24678311
TI  - TLR/NCR/KIR: Which One to Use and When?
AB  - By means of a complex receptor array, Natural killer (NK) cells can recognize
      variable patterns of ligands and regulate or amplify accordingly their effector
      functions. Such NK receptors include old, rather conserved, molecules, such as
      toll-like receptors (TLRs), which enable NK cells to respond both to viral and
      bacterial products, and newer and evolving molecules, such as killer Ig-like
      receptors and natural cytotoxicity receptors, which control NK cytotoxicity and
      are responsible for the elimination of virus-infected or tumor cells without
      damaging self-unaltered cells. In addition, to rapidly gain new functions NK
      cells also can acquire new receptors by trogocytosis. Thus, NK cells may have
      adapted their receptors to different functional needs making them able to play a
      key role in the modulation of critical events occurring in several compartments
      of human body (primarily in SLCs but also in decidua during pregnancy). In this
      review, we will discuss on how the various types of receptors can be used to
      address specific functions in different immunological contexts. 

PMID- 24678313
TI  - Clinical Spectrum of SCID: The Key is in the Thymus?

PMID- 24678314
TI  - The Bright Side of Hematopoiesis: Regulatory Roles of ARID3a/Bright in Human and
      Mouse Hematopoiesis.
AB  - ARID3a/Bright is a DNA-binding protein that was originally discovered for its
      ability to increase immunoglobulin transcription in antigen-activated B cells. It
      interacts with DNA as a dimer through its ARID, or A/T-rich interacting domain.
      In association with other proteins, ARID3a increased transcription of the
      immunoglobulin heavy chain and led to improved chromatin accessibility of the
      heavy chain enhancer. Constitutive expression of ARID3a in B lineage cells
      resulted in autoantibody production, suggesting its regulation is important.
      Abnormal ARID3a expression has also been associated with increased proliferative
      capacity and malignancy. Roles for ARID3a in addition to interactions with the
      immunoglobulin locus were suggested by transgenic and knockout mouse models. Over
      expression of ARID3a resulted in skewing of mature B cell subsets and altered
      gene expression patterns of follicular B cells, whereas loss of function resulted
      in loss of B1 lineage B cells and defects in hematopoiesis. More recent studies
      showed that loss of ARID3a in adult somatic cells promoted developmental
      plasticity, alterations in gene expression patterns, and lineage fate decisions.
      Together, these data suggest new regulatory roles for ARID3a. The genes
      influenced by ARID3a are likely to play pivotal roles in lineage decisions,
      highlighting the importance of this understudied transcription factor. 

PMID- 24678315
TI  - Importance of Both Innate Immunity and Acquired Immunity for Rapid Expulsion of
      S. venezuelensis.
AB  - In the first part of this review, we described the relevant roles of endogenous
      IL-33 for accumulation of ILC2 and eosinophils even in the lungs of Rag2(-/-)
      mice. Type II alveolar epithelial (ATII) cells express IL-33 in their nucleus and
      infection with Strongyloides venezuelensis induces IL-33 production by increasing
      the number of ATII cells possibly by the action of chitin. IL-33 from ATII cells
      induces ILC2 proliferation and at the same time activates them to produce IL-5
      and IL-13, which in combination induce lung eosinophilic inflammation, aiding to
      expel infected worms in the lungs. In the second part, we showed that, although
      AID(-/-) mice normally develop Th2 cells and intestinal mastocytosis after
      infection with S. venezuelensis, they need adoptive transfers of immune sera from
      S. venezuelensis infected mice to obtain the capacity to promptly expel S.
      venezuelensis. Thus, intestinal nematode infection induces various Th2 immune
      responses (e.g., Th2 cell, ILC2, goblet cell hyperplasia, intestinal
      mastocytosis, smooth muscle cell contraction, local and systemic eosinophilia,
      and high serum level of IgE and IgG1). However, all of them are not necessary for
      rapid expulsion of intestinal nematodes. Instead, some combinations of Th2 immune
      responses are essentially required. 

PMID- 24678317
TI  - Bioinformatics-an entry-level avenue for biomedical research in Nepal.

PMID- 24678316
TI  - The plant cell wall in the feeding sites of cyst nematodes.
AB  - Plant parasitic cyst nematodes (genera Heterodera and Globodera) are serious
      pests for many crops. They enter the host roots as migratory second stage
      juveniles (J2) and migrate intracellularly toward the vascular cylinder using
      their stylet and a set of cell wall degrading enzymes produced in the pharyngeal
      glands. They select an initial syncytial cell (ISC) within the vascular cylinder
      or inner cortex layers to induce the formation of a multicellular feeding site
      called a syncytium, which is the only source of nutrients for the parasite during
      its entire life. A syncytium can consist of more than hundred cells whose
      protoplasts are fused together through local cell wall dissolutions. While the
      nematode produces a cocktail of cell wall degrading and modifying enzymes during
      migration through the root, the cell wall degradations occurring during syncytium
      development are due to the plants own cell wall modifying and degrading proteins.
      The outer syncytial cell wall thickens to withstand the increasing osmotic
      pressure inside the syncytium. Furthermore, pronounced cell wall ingrowths can be
      formed on the outer syncytial wall at the interface with xylem vessels. They
      increase the surface of the symplast-apoplast interface, thus enhancing nutrient
      uptake into the syncytium. Processes of cell wall degradation, synthesis and
      modification in the syncytium are facilitated by a variety of plant proteins and
      enzymes including expansins, glucanases, pectate lyases and cellulose synthases,
      which are produced inside the syncytium or in cells surrounding the syncytium. 

PMID- 24678318
TI  - Effect of wireless channels on detection and classification of asthma attacks in
      wireless remote health monitoring systems.
AB  - This paper aims to study the performance of support vector machine (SVM)
      classification in detecting asthma attacks in a wireless remote monitoring
      scenario. The effect of wireless channels on decision making of the SVM
      classifier is studied in order to determine the channel conditions under which
      transmission is not recommended from a clinical point of view. The simulation
      results show that the performance of the SVM classification algorithm in
      detecting asthma attacks is highly influenced by the mobility of the user where
      Doppler effects are manifested. The results also show that SVM classifiers
      outperform other methods used for classification of cough signals such as the
      hidden markov model (HMM) based classifier specially when wireless channel
      impairments are considered. 

PMID- 24678319
TI  - High Prevalence of Infertility among Women with Graves' Disease and Hashimoto's
      Thyroiditis.
AB  - Objectives. To evaluate the prevalence of infertility in women with Graves'
      disease (GD) or Hashimoto's thyroiditis (HT) and associated factors. Material and
      Methods. This cross-sectional study was conducted at the Endocrinology Clinic for
      Thyroid Autoimmune Diseases, with 193 women aged 18-50 years with GD and 66 women
      aged 18-60 years with HT. The women were interviewed to obtain data on their
      gynecological and obstetric history and family history of autoimmune diseases.
      Their medical records were reviewed to determine the characteristics of the
      disease and to confirm association with other autoimmune diseases. Infertility
      was defined as 12 months of unprotected sexual intercourse without conception.
      Results. The prevalence of infertility was 52.3% in GD and 47.0% in HT. Mean age
      at diagnosis was 36.5 years and 39.2 years, in GD and HT, respectively. The mean
      number of pregnancies was lower in women who were 35 years old or younger at
      diagnosis and was always lower following diagnosis of the disease, irrespective
      of age. The only variable associated with infertility was a shorter time of the
      disease in HT. Conclusions. The prevalence of infertility was high in women with
      GD and HT and affected the number of pregnancies in young women. 

PMID- 24678320
TI  - False-negative rate of gram-stain microscopy for diagnosis of septic arthritis:
      suggestions for improvement.
AB  - We quantify the false-negative diagnostic rate of septic arthritis using Gram
      stain microscopy of synovial fluid and compare this to values reported in the
      peer-reviewed literature. We propose a method of improving the diagnostic value
      of Gram-stain microscopy using Lithium Heparin containers that prevent synovial
      fluid coagulation. Retrospective study of the Manchester Royal Infirmary
      microbiology database of patients undergoing synovial fluid Gram-stain and
      culture between December 2003 and March 2012 was undertaken. The initial cohort
      of 1896 synovial fluid analyses for suspected septic arthritis was reduced to 143
      after exclusion criteria were applied. Analysis of our Gram-stain microscopy
      yielded 111 false-negative results from a cohort size of 143 positive synovial
      fluid cultures, giving a false-negative rate of 78%. We report a false-negative
      rate of Gram-stain microscopy for septic arthritis of 78%. Clinicians should
      therefore avoid the investigation until a statistically significant data set
      confirms its efficacy. The investigation's value could be improved by using
      Lithium Heparin containers to collect homogenous synovial fluid samples. Ongoing
      research aims to establish how much this could reduce the false-negative rate. 

PMID- 24678322
TI  - Associated factors of acute chest syndrome in children with sickle cell disease
      in French Guiana.
AB  - A matched case-control study was performed in order to identify some associated
      factors for ACS or to confirm the published data. Controls were children
      hospitalized during the same period for pain crisis who did not develop an ACS
      during hospitalization. Between January 2006 and October 2010, there were 24
      episodes of ACS distributed among 19 patients (8 girls and 11 boys). The median
      age was 7.5 years (range: 3 to 17 years) for the cases and 7 years (range: 3-18
      years) for the controls. Four cases and 11 controls were treated with hydroxyurea
      (HU). In 75% of the cases, the ACS had arisen 24-72 hours following admission.
      The independent factors associated with ACS were average Hb rate <8 g/dL (OR =
      4.96, 95% CI = 1.29-27.34, and P = 0.04), annual number of hospitalizations >3
      (OR = 5.44, 95% CI = 3.59-8.21, and P = 0.003), average length of hospitalization
      >7 days (OR = 3.69, 95% CI = 3.59-8.21, and P = 0.003), and a pathological
      transthoracic echocardiography (TTE) (OR = 13.77, 95% CI = 2.07-91.46, and P =
      0.003). Although the retrospective design and small sample size are weaknesses of
      the present study, these results are consistent with those of previous studies
      and allowed identifying associated factors such as a pathological TTE. 

PMID- 24678321
TI  - Factors related to psychosocial quality of life for children with cerebral palsy.
AB  - Background. Current health services interventions focus on the treatment of the
      musculoskeletal impairments of cerebral palsy (CP). The goal of this study was to
      explore whether the severity of physical symptoms correlates with psychosocial
      quality of life (QOL) among pediatric patients with CP. Methods. A sample of 53
      caregivers of children with CP was surveyed and health status information was
      extracted from patient medical records. Descriptive analysis explored the
      association between the main outcome variable, psychosocial QOL (CP QOL-child),
      and patient demographics, comorbidity (e.g., visual, hearing and feeding
      impairments, language delays, and epilepsy), CP severity (GMFCS), and the receipt
      of family centered care (MPOC-20). Results. Child psychosocial QOL decreased with
      increasing comorbidity but was not associated with CP symptom severity or any
      measured demographic factors. Reporting high levels of family centered care (FCC)
      was associated with higher psychosocial QOL in univariate analysis but was not
      significant when controlling for comorbidities. Conclusion. There is no clear
      connection between symptom severity and psychosocial QOL in children with CP.
      Comorbidity however is strongly associated with psychosocial QOL. Focusing on
      reducing CP comorbidities could have a positive impact on psychosocial QOL. 

PMID- 24678323
TI  - Innovation through Wearable Sensors to Collect Real-Life Data among Pediatric
      Patients with Cardiometabolic Risk Factors.
AB  - Background. While increasing evidence links environments to health behavior,
      clinicians lack information about patients' physical activity levels and
      lifestyle environments. We present mobile health tools to collect and use spatio
      behavioural lifestyle data for personalized physical activity plans in clinical
      settings. Methods. The Dyn@mo lifestyle intervention was developed at the Sainte
      Justine University Hospital Center to promote physical activity and reduce
      sedentary time among children with cardiometabolic risk factors. Mobility,
      physical activity, and heart rate were measured in free-living environments
      during seven days. Algorithms processed data to generate spatio-behavioural
      indicators that fed a web-based interactive mapping application for personalised
      counseling. Proof of concept and tools are presented using data collected among
      the first 37 participants recruited in 2011. Results. Valid accelerometer data
      was available for 5.6 (SD = 1.62) days in average, heart rate data for 6.5 days,
      and GPS data was available for 6.1 (2.1) days. Spatio-behavioural indicators were
      shared between patients, parents, and practitioners to support counseling.
      Conclusion. Use of wearable sensors along with data treatment algorithms and
      visualisation tools allow to better measure and describe real-life environments,
      mobility, physical activity, and physiological responses. Increased specificity
      in lifestyle interventions opens new avenues for remote patient monitoring and
      intervention. 

PMID- 24678324
TI  - Is "Bed Sharing" Beneficial and Safe during Infancy? A Systematic Review.
AB  - Background. There is conflicting evidence regarding the safety and efficacy of
      bed sharing during infancy-while it has been shown to facilitate breastfeeding
      and provide protection against hypothermia, it has been identified as a risk
      factor for SIDS. Methods. A systematic search of major databases was conducted.
      Eligible studies were observational studies that enrolled infants in the first 4
      weeks of life and followed them up for a variable period of time thereafter.
      Results. A total of 21 studies were included. Though the quality of evidence was
      low, bed sharing was found to be associated with higher breastfeeding rates at 4
      weeks of age (75.5% versus 50%, OR 3.09 (95% CI 2.67 to 3.58), P = 0.043) and an
      increased risk of SIDS (23.3% versus 11.2%, OR 2.36 (95% CI 1.97 to 2.83), P =
      0.025). Majority of the studies were from developed countries, and the effect was
      almost consistent across the studies. Conclusion. There is low quality evidence
      that bed sharing is associated with higher breast feeding rates at 4 weeks of age
      and an increased risk of SIDS. We need more studies that look at bed sharing,
      breast feeding, and hazardous circumstance that put babies at risk. 

PMID- 24678325
TI  - Hearing and neurological impairment in children with history of exchange
      transfusion for neonatal hyperbilirubinemia.
AB  - The objective was to determine frequency of sensorineural hearing loss (SNHL),
      identified by abnormal threshold in evoked potentials, absence of otoacoustic
      emissions and behavioral responses, auditory neuropathy (AN) (absence of evoked
      potentials, with preservation of otoacoustic emissions), and neurological
      comorbidity in infants with hyperbilirubinemia (HB) treated with exchange
      transfusion (ET). From a total of 7,219 infants, ET was performed on 336 (4.6%).
      Inclusion criteria were fulfilled in 102; 234 children did not meet criteria (182
      outside of the study period, 34 did not have complete audiological evaluation,
      and 18 rejected the followup). Thirty-five children (34%) were born at-term and
      67 (66%) were preterm. Children had a mean age of 5.5 +/- 3.9 years. Main causes
      of ET were Rh isoimmunization in 48 (47%), ABO incompatibility in 28 (27.5%), and
      multifactorial causes in 26 (25.5%). Fifteen (15%) children presented with SNHL.
      Preterm newborns presented more often with SNHL. Indirect bilirubin level was
      higher in children with SNHL (22.2 versus 18.7 mg/dL, P = 0.02). No cases of AN
      were documented. An increased risk of neurologic sequelae was observed in
      children with SNHL. In conclusion, we disclosed a high frequency of SNHL in
      children with neonatal HB and ET and neurological alterations. No cases of AN
      were observed. 

PMID- 24678326
TI  - Neonatal Meningitis by Multidrug Resistant Elizabethkingia meningosepticum
      Identified by 16S Ribosomal RNA Gene Sequencing.
AB  - Clinical and microbiological profile of 9 neonates with meningitis by
      Elizabethkingia meningosepticum identified by 16S ribosomal gene sequencing was
      studied. All the clinical isolates were resistant to cephalosporins,
      aminoglycosides, trimethoprim-sulfamethoxazole, beta -lactam combinations,
      carbapenems and only one isolate was susceptible to ciprofloxacin. All the
      isolates were susceptible to vancomycin. Six of nine neonates died even after
      using vancomycin, based on susceptibility results. E. meningosepticum meningitis
      in neonates results in high mortality rate. Though the organism is susceptible to
      vancomycin in vitro, its efficacy in vivo is questionable and it is difficult to
      determine the most appropriate antibiotic for treating E. meningosepticum
      meningitis in neonates. 

PMID- 24678327
TI  - IVIG Effects on Erythrocyte Sedimentation Rate in Children.
AB  - Background. Erythrocyte sedimentation rate (ESR) is a valuable laboratory tool in
      evaluation of infectious, inflammatory, and malignant diseases. Red blood cells
      in outside from the body precipitate due to their higher density than the plasma.
      In this study we discuss the IVIG effect on ESR in different diseases and
      different ages. Methods and Materials. Fifty patients under 12 years old who had
      indication to receive IVIG enrolled in this study. Total dose of IVIG was 2 gr/kg
      (400 mg/kg in five days or 2 gr/kg in single dose). ESR before infusion of IVIG
      and within 24 hours after administration of the last dose of IVIG was checked.
      Results. 23 (46%) patients were males and 27 (54%) were females. The mean of ESR
      before IVIG was 31.8 +/- 29.04 and after IVIG it was 47.2 +/- 36.9; this
      difference was meaningful (P = 0.05). Results of ESR changes in different age
      groups, 6 patients less than 28 days, 13 patients from 1 month to 1 year, 20
      patients from 1 to 6 years old, and 11 patients from 6 to 12 years have been
      meaningful (P = 0.001, P = 0.025, and P = 0.006, resp.). Conclusion. In patients
      who are receiving IVIG as a therapy, ESR increased falsely (noninflammatory
      rising); therefore use of ESR for monitoring of response to treatment may be
      unreliable. Although these results do not apply to neonatal group, we suggest
      that, in patients who received IVIG, interpretation of ESR should be used
      cautiously on followup. 

PMID- 24678328
TI  - Efficacy and effectiveness of extended-valency pneumococcal conjugate vaccines.
AB  - The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be
      highly efficacious against invasive pneumococcal diseases and effective against
      pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in
      major changes in the epidemiology of pneumococcal diseases. However, pneumococcal
      vaccines induce serotype-specific immunity, and a relative increase in non
      vaccine serotypes has been reported following the widespread use of PCV7, leading
      to a need for extended serotype coverage for protection. PCV10 and PCV13 have
      been licensed on the basis of noninferiority of immunogenicity compared to a
      licensed conjugate vaccine. In this article, we aimed to review important data
      regarding the efficacy and effectiveness of the extended-coverage PCVs published
      or reported thus far and to discuss future implications for pneumococcal vaccines
      in Korea. After the introduction of PCV10 and PCV13, within a short period of
      time, evidence of protection conferred by these vaccines against invasive and
      mucosal infections caused by most of the serotypes included in the vaccines is
      accumulating. The choice of vaccine should be based on the changes in the
      dynamics of pneumococcal serotype distribution and diseases in the region where
      the vaccines are to be used. Continuous surveillance is essential for the
      appropriate use of pneumococcal vaccines and evaluation of the impact of PCVs on
      pneumococcal diseases. 

PMID- 24678329
TI  - Antibiotics resistance of Helicobacter pylori and treatment modalities in
      children with H. pylori infection.
AB  - Pediatric infection with Helicobacter pylori may occur early in childhood and
      persist lifelong. Global pediatric clinical studies have reported a decreasing
      tendency in the overall rate of H. pylori eradication. In pediatric patients with
      H. pylori infection, pediatric patients with peptic ulcer, and the first-degree
      relatives of patients with a history of gastric cancer, it is commonly
      recommended that H. pylori strains be eradicated. Antibiotic drug resistance to
      H. pylori, which has been reported to vary widely between geographic regions, is
      mainly associated with treatment failure in these patients. It is therefore
      imperative that the antibiotic resistance rates of H. pylori in children and
      adolescents be meticulously monitored across countries and throughout geographic
      regions. This paper particularly focuses on the antibiotic drug resistance of H.
      pylori and the thearpy of pediatric H. pylori infection cases. 

PMID- 24678330
TI  - Head circumference alone at birth, is it practical?

PMID- 24678331
TI  - Clinical features of macrocephaly at birth in Korea.
AB  - PURPOSE: This study aimed to investigate the clinical features of macrocephaly at
      birth in Korea using ultrasonography. METHODS: We retrospectively investigated
      the medical records of full-term birth neonates in Cheil General Hospital &
      Women's Healthcare Center from January 2000 to June 2012. The following
      parameters were recorded and analyzed: gestational age, sex, birth weight,
      height, occipitofrontal circumference (OFC), physical examination, perinatal
      problems, and ultrasonography results. Macrocephaly was diagnosed when the OFC
      was greater than two standard deviations, based on the 2007 Korean National
      Growth Charts. RESULTS: There were 75 neonates with macrocephaly at birth (52
      boys and 23 girls), with a mean OFC of 38.1+/-0.49 cm. A comparison of the birth
      weight and height with the OFC value showed that height was correlated with OFC
      (r=0.35) but birth weight was not correlated with OFC (r=0.06). There were no
      remarkable findings in 56 cases (75%). Germinal matrix hemorrhage was identified
      in 10 cases (13%). An enlarged cerebrospinal fluid space was found in 5 cases
      (6.7%). There were 3 cases of mega-cisterna magna (4%), 1 case of
      ventriculomegaly, and 1 case of an enlarged interhemispheric space (6 mm) among
      these patients. In addition, a choroid plexus cyst was seen in 1 case.
      Mineralizing vasculopathy in both basal ganglia with no evidence of congenital
      infection was found in 2 cases and an asymptomatic subarachnoid hemorrhage was
      found in 1 case. CONCLUSION: Our results indicate that macrocephaly at birth has
      benign ultrasonography findings and shows a pattern of male dominance.

PMID- 24678332
TI  - The association of blood pressure with body mass index and waist circumference in
      normal weight and overweight adolescents.
AB  - PURPOSE: Overweight can be defined by the body mass index (BMI) and is likely
      associated with an increased cardiovascular disease risk. However, waist
      circumference (WC), a central adiposity index, may be a better indicator of
      cardiovascular disease risk. Studies comparing the effects of BMI and WC on
      cardiovascular risk factors, such as high blood pressure (BP), are rare in
      adolescents. METHODS: We analyzed the correlations of BMI and WC with BP in 3,363
      Korean adolescents (aged 10-19 years), using data from the Korean National Health
      and Nutrition Examination Surveys (2009-2011). RESULTS: Systolic BP (SBP) in both
      sexes and diastolic BP (DBP) in boys were higher in the high BMI (>85th
      percentile) and high WC (>90th percentile) groups. High BMI and high WC were
      positively correlated with high SBP (>90th percentile) in both sexes, and high
      DBP (>90th percentile), in boys. BMI maintained its positive associations with
      SBP, DBP, high SBP, and high DBP in the normal weight (BMI<=85th percentile) and
      overweight (BMI>85th percentile) groups in both boys and girls, as well as in all
      subjects of both sexes, even after adjustment for WC. However, WC did not
      correlate with SBP, DBP, high SBP, or high DBP after adjustment for BMI in any
      group in either sex. CONCLUSION: In Korean adolescents, BMI correlated better
      with BP and high BP levels than WC. Further, BMI was positively associated with
      BP and high BP in the normal weight group as well as in the overweight group.

PMID- 24678334
TI  - Griscelli syndrome type 2: a novel mutation in RAB27A gene with different
      clinical features in 2 siblings: a diagnostic conundrum.
AB  - Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by
      mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation,
      immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers
      who had GS2 with clinically diverse manifestations. The elder brother presented
      with a purely neurological picture, whereas the younger one presented with fever,
      pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that
      cutaneous hypopigmentation was a common feature between the brothers, genetic
      analysis for Griscelli syndrome was performed. As the elder sibling had died,
      mutation analysis was only performed on the younger sibling, which revealed a
      novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single
      base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same
      mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both
      siblings. The atypical features of GS2 in these cases are a novel mutation,
      isolated neurological involvement in one sibling, association with erythema
      nodosum, and 2 distinct clinical presentations in siblings with the same genetic
      mutation. 

PMID- 24678333
TI  - Characteristics of thyroid nodules in infant with congenital hypothyroidism.
AB  - PURPOSE: This study aimed to assess the characteristics of thyroid nodules among
      infants diagnosed with congenital hypothyroidism. METHODS: A retrospective study
      of 660 infants (374 males, 286 females) diagnosed with congenital hypothyroidism
      was carried out at the Pediatric Endocrine Clinic in Soonchunhyang University
      Hospital, Korea, between May 2003 and February 2013. The average age at diagnosis
      was 1.16+/-1.68 months. RESULTS: Of the 28 patients (4.2%) with thyroid nodules,
      17 (2.6%) had cystic thyroid nodules and 11 (1.6%) had solid thyroid nodules.
      There were no significant differences in gender or age between congenital
      hypothyroidism patients who hadthyroid nodules and those who did not. All nodules
      were asymptomatic. The average age at diagnosis of congenital hypothyroidism with
      nodules was 1.42+/-1.39 months. All detected nodules measured less than 1 cm in
      diameter. Twenty-two of the 28 infants (78.6%) had only one nodule, while
      multiple nodules were found in 6 infants (21.4%). Of the 28 infants diagnosed
      with nodules, 16 underwent thyroid ultrasonography during follow-up and 8 of them
      (50%) showed no signs of nodules at thyroid ultrasonography. CONCLUSION: The
      prevalence of thyroid nodules in infants with congenital hypothyroidism was 4.2%.
      Most thyroid nodules were small in size and benign, disappearing during follow-up
      observation. We therefore conclude that thyroid nodules in infants with
      congenital hypothyroidism can simply be observed and do not require direct
      treatment.

PMID- 24678337
TI  - Cytodiagnosis of scar endometriosis.

PMID- 24678335
TI  - Shiga toxin-associated hemolytic uremic syndrome complicated by intestinal
      perforation in a child with typical hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal
      failure in childhood and is primarily diagnosed in up to 4.5% of children who
      undergo chronic renal replacement therapy. Escherichia coli serotype O157:H7 is
      the predominant bacterial strain identified in patients with HUS; more than 100
      types of Shiga toxin-producing enterohemorrhagic E. coli (EHEC) subtypes have
      also been isolated. The typical HUS manifestations are microangiopathic hemolytic
      anemia, thrombocytopenia, and renal insufficiency. In typical HUS cases, more
      serious EHEC manifestations include severe hemorrhagic colitis, bowel necrosis
      and perforation, rectal prolapse, peritonitis, and intussusceptions. Colonic
      perforation, which has an incidence of 1%-2%, can be a fatal complication. In
      this study, we report a typical Shiga toxin-associated HUS case complicated by
      small intestinal perforation with refractory peritonitis that was possibly
      because of ischemic enteritis. Although the degree of renal damage is the main
      concern in HUS, extrarenal complications should also be considered in severe
      cases, as presented in our case. 

PMID- 24678339
TI  - Introduction: mental capacity and value neutrality.

PMID- 24678338
TI  - Granulomatous inflammation and organizing pneumonia: Role of computed tomography
      guided lung fine needle aspirations, touch preparations and core biopsies in the
      evaluation of common non-neoplastic diagnoses.
AB  - BACKGROUND: Fine-needle aspirations (FNAs) and core biopsies (CBs), with or
      without touch preparations (TPs), are performed to characterize pulmonary
      lesions. Although a positive (P) or suspicious report is sufficient for further
      management, the significance of unsatisfactory (U), negative (N) and atypical (A)
      cytological diagnoses remains uncertain. The aims of the study were to correlate
      U, N and A cytological diagnoses with histological and/or clinical/radiological
      follow-up and evaluate the utility of FNAs, TPs and CBs. MATERIALS AND METHODS:
      We performed a retrospective search and examined 30 consecutive computed
      tomography-guided transthoracic U, N and A lung FNAs (n = 23) and TPs (n = 7)
      with surgical pathology (SP) (n = 17) and/or clinical/radiological follow-up (n =
      13) and compared them to 10 SP-confirmed P FNAs, which served as controls.
      RESULTS: The 30 FNAs and TPs were from 29 patients. All 6 U specimens were
      scantly cellular. Granulomas, the most common specific benign cytological
      diagnosis, were evident in 8 (of 13) and 7 (of 11) N and A cytology cases,
      respectively. Histology corroborated the presence of granulomas identified on
      cytology. Organizing pneumonia was the second leading benign specific diagnosis
      (5/17), but it was rendered on histology (n = 5) and not FNAs or TPs. Evaluation
      of the A cases revealed that type II pneumocytes were the source of "atypical",
      diagnoses often associated with granulomas or organizing pneumonia and lacked 3-D
      clusters evident in all P cases. DISCUSSION: U, N and A FNAs and TPs lacked 3-D
      clusters seen in carcinomas and were negative on follow-up. Granulomas and
      organizing pneumonia were the most common specific benign diagnoses, but the
      latter was recognized on histology only. In the absence of a definitive FNA
      result at the time of on-site assessment, a CB with a TP containing type II
      pneumocytes increases the likelihood of a specific benign diagnosis.

PMID- 24678340
TI  - Capacity, value neutrality and the ability to consider the future.
AB  - Calls for the adoption of a universal capacity approach to replace dedicated
      mental health law are motivated by the idea that the measures designed to protect
      patient autonomy in legislation such as the Mental Capacity Act 2005 should apply
      to everyone, including people with a psychiatric diagnosis. In this article it is
      argued that a diachronic perspective on questions of mental capacity is necessary
      if capacity law is to play this broader role, but that employing this perspective
      in assessments of capacity undermines central patient autonomy preserving
      features of the legislation, which presents a moral dilemma.

PMID- 24678341
TI  - Television's Cultivation of American Adolescents' Beliefs about Alcohol and the
      Moderating Role of Trait Reactance.
AB  - Cultivation research has shown that heavy television viewing is linked to
      audiences' generalized, and often skewed, views of reality. This research
      investigates whether television viewing is related to adolescents' views about
      the consequences of drinking and whether psychological trait reactance moderates
      this cultivation effect. Results from a survey of 445 American teenagers show
      that cumulative exposure to television is linked to reduced beliefs about
      alcohol's negative consequences and greater intentions to drink. These effects
      were greater for adolescents low on trait reactance. This research adds to the
      general psychological research on trait reactance as a moderator of media
      influences and makes a substantive contribution towards furthering our
      understanding of the media and public health concerns that surround risky
      adolescent behaviors.

PMID- 24678342
TI  - Comorbid mental health and substance abuse issues among individuals in recovery
      homes: Prospective environmental mediators.
AB  - Individuals with comorbid internalizing psychological symptoms and substance
      abuse issues often have more negative outcomes and evidence a relative disparity
      in treatment gains compared to those with only substance abuse issues. The
      present study examined social mechanisms over time for individuals living in self
      governed recovery homes (Oxford Houses) such as 12-step group activities and
      social support, which likely influence both abstinence and psychological
      outcomes. Participants (n = 567) from a national United States sample of Oxford
      Houses completed baseline and multiple follow-up self-report assessments over a
      one-year period. A structural equation model was utilized to evaluate predicted
      relationships among baseline symptoms, 12-step activities, social support, and
      outcome variables. Results indicated that internalizing symptoms were associated
      with subsequent mutual help activities, but not directly with social support.
      Living in an Oxford House for six months and number of 12-step meetings attended
      were partially mediated by social support variables in predicting abstinence
      outcomes, but not psychological outcomes. Environments such as Oxford Houses may
      be viable options for recovering individuals with comorbid internalizing
      psychological problems, although social support mechanisms primarily promote
      abstinence. Implications for future research and for Oxford House policies are
      discussed.

PMID- 24678343
TI  - The Aspirin Foundation Scientific Conference: the history, the present state and
      the future of aspirin prophylaxis.
AB  - The 2013 Aspirin Foundation Conference covered a range of topics from clinical
      and medical history, epidemiology, health economics, and the current uses of
      aspirin in general practice and in the treatment and prevention of cancer. The
      use of aspirin as primary prevention in people at risk of atherosclerotic events
      is now well known, but its use as a preventative agent in some cancer types is
      still under discussion, and data on colorectal and lung cancer were presented at
      this meeting. The potential use of aspirin in preventing vascular disease in HIV
      patients was also discussed. The cost effectiveness of aspirin as a primary
      prevention strategy was discussed for the first time in this series of meetings. 

PMID- 24678344
TI  - Cancer trends and risk factors in Cyprus.
AB  - Cyprus, a European Union member state, is a small island in the Mediterranean
      with a population approaching 900,000 people. Cancer is the second leading cause
      of death; more therapeutic options for any patient with the disease are available
      in a central oncology centre in the capital of the island (Nicosia) and fewer
      therapeutic options (e.g. chemotherapy and hormone therapy only) in a few other
      public hospitals. Palliative care is offered in several hospices and hospitals,
      although the field needs improvement. With regards to screening, a national
      breast cancer screening programme has been in place countrywide since 2007 and is
      offered free of charge to women between the ages of 50 and 69 years, while
      colorectal and prostate cancer screening is performed on an individual basis (a
      pilot programme for colorectal cancer screening was recently initiated). Genetic
      testing is available for breast and colon cancer. To improve understanding of the
      causes of cancer in the country, a cancer research centre was established in 2010
      (Mediterranean Centre for Cancer Research). Recent epidemiologic work has
      revealed increasing cancer trends in Cyprus; prostate cancer is the most common
      in men and breast cancer is the most common in women. Interestingly, thyroid
      cancer incidence in women has been rising from 1998 to 2008. Cancer of the colon
      and rectum is also on the rise affecting both sexes. Overall, cancer incidence in
      Cyprus is lower than other EuroMed countries with similar lifestyle and
      geography. 

PMID- 24678345
TI  - Tales from the Jazz ASH: highlights from the 2013 American Society of Haematology
      meeting.
AB  - The 55th annual ASH meeting was held in pleasant New Orleans and was the largest
      in its history, with 22,495 participants coming from 113 nations. A 'bench-to
      bedside and back' attitude characterises haematology probably more than any other
      discipline in medicine and, as usual, this was reflected in the extremely wide
      breadth of the topics covered, including the last results from clinical trials
      and cutting-edge advancements in basic science. This year, the balance was
      arguably skewed: few truly clinical practice-changing results were presented. On
      the other hand, a great number of basic and translational studies significantly
      increased our understanding of the biology of numerous malignancies and heralded
      the coming of age of disruptive technologies. Namely, above all, next generation
      sequencing and T cell engineering-based cell therapy. 

PMID- 24678346
TI  - How much survival benefit is necessary for breast cancer patients to opt for
      adjuvant chemotherapy? Results from a Chilean survey.
AB  - BACKGROUND: Breast cancer (BC) is the leading cause of cancer death in Chilean
      women. Adjuvant chemotherapy decreases recurrence and death from BC. The
      recommendation to indicate chemotherapy is complex. Adjuvant! Online is a
      valuable computational tool to predict survival benefit obtained with adjuvant
      systemic therapy. Previous studies in Caucasian patients with BC showed that they
      are willing to receive chemotherapy for a small benefit. No studies, to our
      knowledge, have been done in the Hispanic or Latino populations. METHODS: We
      interviewed females with BC who had previously received adjuvant chemotherapy.
      Age, stage at presentation, time since last chemotherapy, type of chemotherapy,
      marital status, number of children, and level of education were recorded. We used
      the graphic representation from Adjuvant! Online to question each patient on how
      much survival benefit she required to accept chemotherapy. RESULTS: There were
      101 women surveyed. The average age was 55.9 (+/-10.2), 54.5% had involved lymph
      nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females
      accepted chemotherapy for an absolute survival benefit of 1% or less. In a
      multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018)
      were associated with lower survival benefit required to opt for chemotherapy.
      CONCLUSION: In our study, the acceptance of chemotherapy by the Hispanic
      population requires minimal survival benefit and is in agreement with the
      Caucasian population reported elsewhere. To our knowledge, our report is the
      first study that evaluates the perception of Latino patients regarding the
      benefit of chemotherapy in early BC.

PMID- 24678347
TI  - Behavioral Genetic Approaches and Family Theory.
AB  - Family theories have been founded on research that cannot discriminate genetic
      and environmental influences and, consequently, most theories do not have highly
      developed models of gene-environment interplay in families. Behavioral genetic
      approaches, which can identify gene-environment interplay, have typically not
      been driven by family theories and have lacked adequate measurement of family
      processes. In this article, the authors describe behavioral genetic mechanisms
      and methods using representative examples of research on family processes,
      highlighting the advantages of an integrated approach. New directions in research
      and theory driven by an integrated approach are discussed.

PMID- 24678348
TI  - Effect of Static Pre-stretch Induced Surface Anisotropy on Orientation of
      Mesenchymal Stem Cells.
AB  - Mechanical cues in the cellular environment play important roles in guiding
      various cell behaviors, such as cell alignment, migration, and differentiation.
      Previous studies investigated mechanical stretch guided cell alignment pre
      dominantly with cyclic stretching whereby an external force is applied to stretch
      the substrate dynamically (i.e., cyclically) while the cells are attached onto
      the substrate. In contrast, we created a static pre-stretched anisotropic surface
      in which the cells were seeded subsequent to stretching the substrate. We
      hypothesized that the cell senses the physical environment through a more active
      mechanism, namely, even without external forces the cell can actively apply
      traction and sense an increased stiffness in the stretched direction and align in
      that direction. To test our hypothesis, we quantified the extent of pre-stretch
      induced anisotropy by employing the theory of small deformation superimposed on
      large and predicted the effective stiffness in the stretch direction as well as
      its perpendicular direction. We showed mesenchymal stem cells (MSC) aligned in
      the pre-stretched direction, and the cell alignment and morphology were dependent
      on the pre-stretch magnitude. In addition, the pre-stretched surface demonstrated
      an ability to promote early myoblast differentiation of the MSC. This study is
      the first report on MSC alignment on a statically pre-stretched surface. The cell
      orientation induced by the pre-stretch induced anisotropy could provide insight
      into tissue engineering applications involving cells that aligned in vivo in the
      absence of dynamic mechanical stimuli.

PMID- 24678349
TI  - Clinical outcomes in patients with metastatic renal cell carcinoma receiving
      everolimus or temsirolimus after sunitinib.
AB  - INTRODUCTION: There are little data on the clinical activity of temsirolimus (TM)
      and everolimus (EV) when used as second-line therapy after sunitinib (SU) in
      patients with metastatic renal cell carcinoma (mRCC). METHODS: Patients with mRCC
      treated with EV or TM after SU were included in this retrospective analysis.
      Progression-free survival (PFS), time to sequence failure (TTSF) from the start
      of SU to disease progression with EV/TM and overall survival (OS) were estimated
      using Kaplan-Meier method and compared across groups using the log-rank test. Cox
      proportional hazards models were applied to investigate predictors of TTSF and
      OS. RESULTS: In total, 89 patients (median age 60.0 years) were included. At
      baseline 43% were classified as MSKCC good-risk, 43% as intermediate-risk and 14%
      as poor-risk. Median OS was 36.3 months and median TTSF was 17.2 months. Sixty
      five patients received SU-EV and 24 patients SU-TM. Median PFS after the second
      line treatment was 4.3 months in the EV group and 3.5 months in the TM group (p =
      0.63). Median TTSF was 17.0 and 18.9 months (p = 0.32) and the OS was 35.8 and
      38.3 months (p = 0.73) with SU-EV and SU-TM, respectively. The prognostic role of
      initial MSKCC was confirmed by multivariable analysis (hazard ratio 1.76, 95%
      confidence interval 1.08-2.85. p = 0.023). CONCLUSIONS: This study did not show
      significant differences in terms of disease control and OS between EV and TM in
      the second-line setting. EV remains the preferred mTOR inhibitor for the
      treatment of mRCC patients resistant to prior tyrosine kinase inhibitor
      treatment.

PMID- 24678350
TI  - Is there an urban-rural-gradient in patients with urinary incontinence?
AB  - INTRODUCTION: The objective of this study was to determine whether the responses
      to the same questionnaire differ between women living in a large city and women
      living in a rural area. METHODS: We evaluated the medical records of 88 patients
      living in the large city of Cologne and of 86 patients living in Bruhl and its
      surrounding rural regions. The responses on the International Consultation on
      Incontinence Questionnaire-Short Form (ICIQ-SF) of 88 patients who suffer from
      urinary incontinence and live in a large city were compared to the responses 86
      patients who live the rural region of Bruhl. In addition, ages, frequency of
      micturition, use of pads, prior and desired treatment were compared. Limitations
      of this study include its retrospective study design and the absence of
      sociodemographic data. Furthermore, the use of a pad test could objectify the
      extent of incontinence. RESULTS: On average, patients from Cologne used of 6.2
      pads and patients from Bruhl used 3 pads. Patients from the large city scored 14
      out of 21 points on the ICIQ-SF, and women from Bruhl scored 11 out of 21 points.
      This difference was significant. Patients from Cologne had received medicinal
      treatment or physical therapy significantly more often. CONCLUSION: The results
      suggest that urinary incontinence is perceived as a greater impairment by
      patients residing in (large) cities compared to patients residing in rural areas.
      An urban-rural gradient in patients with urinary incontinence can be described.

PMID- 24678351
TI  - The diagnosis and treatment of primary adrenal lipomatous tumours in Chinese
      patients: A 31-year follow-up study.
AB  - INTRODUCTION: Adrenal lipomatous tumours (ALTs) are rarely encountered in
      clinical practice and consequently little is known about their clinical features.
      METHODS: We analyze the clinical features, diagnosis and treatment of ALTs based
      on cases presenting at a single centre over a 31-year period. We reviewed
      clinical data from patients with primary adrenal tumours treated at the Ruijin
      Hospital, Shanghai between January 1980 and December 2010. RESULTS: A total of 73
      cases of primary ALTs in 22 men and 51 women (mean age 51.1+/-14.2 years) were
      reviewed. The ALTs included 65 myelolipomas (89.0%), 3 lipomas (4.1%), 2
      angiomyolipomas (2.7%), 2 teratomas (2.7%), and 1 liposarcoma (1.4%). Of the
      total 73 patients, 24 of them had tumours in the left adrenal gland, 47 in the
      right gland and 2 had bilateral tumours. In total, 51 patients underwent open
      surgery and 22 laparoscopic surgery. CONCLUSION: Myelolipoma is predominant among
      the various types of lipomatous adrenal gland tumours; it accounts for about 90%
      of all cases. Surgery is recommended for tumours >=3.5 cm in diameter, for all
      cases of symptomatic tumour, and for cases of teratoma or liposarcoma identified
      by preoperative imaging.

PMID- 24678352
TI  - Association between R.E.N.A.L. nephrometry score and perioperative outcomes
      following open partial nephrectomy under cold ischemia.
AB  - INTRODUCTION: We investigate the clinical significance of the R.E.N.A.L.
      nephrometry score for renal neoplasm following open partial nephrectomy (PN)
      under cold ischemia. METHODS: A retrospective analysis was conducted using
      clinical data of 98 consecutive patients with clear cell renal cell carcinoma who
      underwent open PN by a single surgeon from December 2000 to September 2012.
      Tumour complexity was stratified into 3 categories: low (4-6), moderate (7-9) and
      high (10-12) complexity. Perioperative outcomes, such as complications, cold
      ischemic time, estimated blood loss and renal function, were analyzed according
      to the complexity by NS. Complications were stratified using the Clavien-Dindo
      classification system. RESULTS: Tumour complexity according to nephrometry score
      was assessed as low in 16 (16.3%), moderate in 48 (49.0%) and high in 34 (34.7%).
      The median cold ischemic time did not differ significantly among the 3 groups
      (36.0 minutes in low-, 40 minutes in moderate- and 43 minutes in the high
      complexity group, p = 0.421). Total complications did not differ significantly (2
      (2.0%) in low, 4 (4.1%) in moderate and 4 (4.1%) in high, p = 0.984). Each Grade
      3 complication occurred in the moderate (urine leakage) and high groups
      (lymphocele). Postoperative renal functional outcomes were similar among the
      groups (p = 0.729). Only mean estimated blood loss was significantly different
      with nephrometry score (p = 0.049). CONCLUSIONS: The nephrometry score, as used
      in an open PN series under cold ischemia, was not significantly associated with
      perioperative outcomes (i.e., ischemia time, complications, renal functional
      preservation).

PMID- 24678353
TI  - Male circumcision performed with 8-figure non-absorbable suture technique.
AB  - INTRODUCTION: We analyze the outcome of circumcisions performed with 8-figure non
      absorbable suture (8FNS) and assess the feasibility of using the technique in
      male circumcision. METHODS: We randomly divided 317 patients who would undergo
      circumcision between February 2009 and January 2012 into 2 groups. Each group was
      subdivided into children (age range: 7 to 15 years) and adult (range: 16 to 85
      years). In the experiment group (n =166), we used 8FNS and in control group (n =
      151), commonly absorbable suture (CAS) were used for the circumcised wound
      closure. The results of 2 groups were compared. We also performed a cost analysis
      and a mean 6-month follow-up (range: 1-12). Chi-square and Student's t-test were
      used in statistical analysis. Differences were considered significant (p < 0.05).
      RESULTS: No patients were required to remove their sutures postoperatively. Among
      them, the sutures of the 8FNS for circumcision fell off spontaneously within 9
      days (6.2 +/- 1.57). There was no statistically significant difference between
      the 2 groups in surgical duration (16.2 +/- 1.73 vs. 15.8 +/- 2.01) and follow-up
      time (6.4 +/- 3.82 vs. 6.2 +/- 2.39). The overall complication rate of the 2
      groups was 6.63% and 10.53% (p = 0.15), respectively. In addition, the
      complication rate among the adults was significantly lower in the 8FNS group
      compared to children (2.53% vs. 10.34%, p = 0.04). Also, the average cost (in US
      dollars) of 8FNS for circumcision was $20.7 +/- $3.83 less than $35.8 +/- $5.02
      of CAS, which is a very significant difference (p < 0.0001). CONCLUSIONS: 8FNS
      for circumcision is feasible, easy, safe and cost-effective, especially for adult
      males.

PMID- 24678354
TI  - Age-stratified distribution of metastatic sites in bladder cancer: A population
      based analysis.
AB  - INTRODUCTION: Urothelial carcinoma of the urinary bladder (UCUB) is the most
      common malignancy of the urinary tract. We examined the distribution of site
      specific metastases in patients with UCUB according to age and we assessed
      contemporary recommendations proposed by guidelines with regard to distant
      metastases. METHODS: Patients with metastatic UCUB (mUCUB) were abstracted from
      the Nationwide Inpatient Sample (1998-2007). Age was stratified into quartiles:
      <=63, 64-72, 73-79 and >=80 years. Cochran-Armitage trend test and multivariable
      logistic regression analysis tested the relationship between age and the rate of
      metastases. Finally, we identified patients at high risk of brain or bone
      metastases. RESULTS: Within 7543 patients with mUCUB, 25%, 24%, 23%, 19%, 18% and
      3% had lymph node, bone, urinary, lung and liver metastases, respectively.
      Overall, the rate of concomitant metastases was 29%. The rate of multiple
      metastatic sites decreased with increasing age (p < 0.001). This was confirmed in
      patients with lung, bone, liver, urinary system and brain metastases (all p <=
      0.04). The rate of bone metastases was 15.0% in patients with exclusive abdominal
      metastases and 40.0% in patients with abdominal, thoracic and brain metastases.
      The rate of brain metastases was 1% in patients with exclusive abdominal
      metastases and 7% in patients with thoracic and bone metastases. Our findings are
      limited by the retrospective nature of the analyses. CONCLUSIONS: We report a
      higher number of concomitant metastatic sites in young UCUB patients. Bone
      metastases are frequent in all patient groups, whereas brain metastases are
      common in UCUB patients with thoracic and/or bone metastases.

PMID- 24678355
TI  - [Not Available].

PMID- 24678356
TI  - Renal lymphangiectasia presenting with hypertension and polycythemia.
AB  - We report a very rare case of renal lymphangiectasia, an accumulation of lymph in
      the renal lymphatic system secondary to obstruction. Our patient presented to his
      family doctor for an annual check-up which resulted with high blood pressure and
      polycythemia. An ultrasound was performed and revealed a large right perirenal
      collection. A year later, a controlled abdominal computed tomography scan showed
      a progression and compression of perirenal collection on the right kidney, as
      well as apparition of a left perirenal collection. Percutaneous drainage of both
      collections was unsuccessful. Laparoscopy-guided marsupialisation was performed
      and successful. Blood pressure lowered to normal range without medication. The
      patient's hemoglobin level decreased within normal range after 3 additional
      phlebotomies postoperatively. 

PMID- 24678357
TI  - Collecting duct of Bellini renal carcinoma with psoas muscle recurrence: A case
      report and review of literature.
AB  - Collecting duct carcinoma (CDC) is a rare type of renal carcinoma with an
      aggressive course and poor treatment response. Up to date, there are only few
      reports of CDC, which may be due to unrecognized or unfamiliarity of its features
      and characteristics. We report a case of CDC in a 63-year-old male who initially
      presented with localized disease, and developed psoas muscle metastasis 15 months
      after partial nephrectomy with good surgical margins. No guidelines currently
      exist for the management of CDC; however, aggressiveness of the disease warrants
      close surveillance and consideration of adjuvant therapy even in patients with
      localized tumours. We postulate that CDC in its localized stage can be managed by
      partial nephrectomy, while preserving renal function; however, it is also
      important to consider a good oncologic outcome by administering adjuvant therapy,
      such as chemotherapy, and targeted therapy for a better prognostic outcome. 

PMID- 24678358
TI  - A unique case of kidney's collecting system MALT lymphoma.
AB  - Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas)
      are mostly seen in the gastrointestinal tract. MALT lymphomas involving kidney
      are extremely rare. We report on a case of MALT lymphomas of the kidney. A 74
      year-old woman presented with an episode of gross hematuria and right flank pain.
      In renal sonography, we found a hypoecho lesion measuring 61 * 58 * 44 mm in the
      lower pole of right kidney. A computed tomography scan revealed an enlarged
      hypodense soft tissue measuring 62 * 42 * 37 mm within the pelvic brim of the
      right kidney, with extension to the proximal portion of the ipsilateral ureter
      and engulfed it. The patient underwent a right radical nephrectomy. The pathology
      specimen indicated a lymphoprolifrative disorder involving the kidney and ureter.
      To obtain a definitive diagnosis, we used an immunohistochemistry, which
      confirmed the diagnosis of a MALT lymphoma. 

PMID- 24678359
TI  - Concomitant testicular seminoma and ectopic adrenal tissue of the cord in a 45
      year-old male.
AB  - Aberrant adrenal tissue near the adrenal gland is common, but the finding of
      ectopic adrenal tissue in structures around the spermatic cord and testis is
      rare. We describe a case of concomitant seminoma and ectopic adrenal tissue of
      the spermatic cord occurring in an adult patient who had undergone orchidopexy as
      a child. 

PMID- 24678360
TI  - Outpatient tubeless percutaneous nephrolithotomy and concomitant
      cystolitholapaxy.
AB  - Percutaneous nephrolithotomy (PCNL) is a widely employed endourologic procedure
      to remove renal stones. Traditionally, PCNL has been performed on an inpatient
      basis, with patients routinely hospitalized postoperatively. Given the ongoing
      rising healthcare costs, a shift toward outpatient surgery is desirable. We
      report the case of a 21-year-old female who was safely discharged a few hours
      following uncomplicated tubeless PCNL and concomitant cystolitholapaxy for a
      stent with encrustation on its distal coil. To the best of our knowledge, this is
      the first published case of tubeless PCNL with concomitant cystolitholapaxy
      performed on an entirely outpatient basis. 

PMID- 24678361
TI  - A rare case of testicular metastasis of bladder transitional cell carcinoma.
AB  - Metastases from bladder transitional cell carcinoma (TCC) to the testis are very
      rare. These are usually found on autopsy and occur in advanced or metastatic
      bladder cancers. More common, known primary tumors that metastasize to the testis
      include prostate, lungs, melanoma, gastro-intestinal tract and the kidney. We
      report a rare case of solitary and synchronous metastatic TCC of the bladder to
      the testis, discovered on histological examination. This case illustrates that
      metastatic neoplasm to uncommon sites should be considered in the differential
      diagnosis for patients with a history of advanced bladder TCC. 

PMID- 24678362
TI  - Case report and literature review of a rare diagnosis of ossifying renal tumour
      of infancy.
AB  - One must entertain a broad differential diagnosis for infants presenting with
      gross hematuria. Initial workup includes urine analysis, serum laboratory values
      and abdominal ultrasound. We describe an infant presenting with gross hematuria
      found to have a calcified renal mass upon initial ultrasound and subsequent
      computed tomography scan. We considered a differential diagnosis of, but not
      exclusive to, staghorn calculi, nephroblastoma, Wilms' tumour, mesoblastic
      nephroma and ossifying renal tumour of infancy (ORTI). A nephrectomy was
      performed, and the pathology report identified the calcified mass as an ORTI. 

PMID- 24678363
TI  - Ovarian metastasis of clear cell renal cell carcinoma: A case report.
AB  - We report on a 61-year-old woman with a history of right-sided nephrectomy for
      clear cell renal cell carcinoma (RCC) occurring 21 years ago; she currently
      presented with a bilateral ovarian tumour. Histologically, the tumour of both
      ovaries was clear cell carcinoma. Immunohistochemically, the tumour cells were
      positive for vimentin, RCC marker, epithelial membrane antigen, cytokeratin AE1/3
      and CD10. Cytokeratin 7, CA125, HMWCK, estrogen and progesterone receptors were
      all negative. Based on the morphology and immunophenotype of the tumour, we
      established a diagnosis of late metastasis of RCC in the ovaries. A postoperative
      abdominal computed tomography scan, however, revealed a tumour mass solely in the
      left kidney, which had not been visible in the preoperative ultrasound. The
      patient underwent nephron-sparing surgery and a biopsy showed the tumour to be
      clear cell RCC. Metastasis of RCC to the ovaries is rare, and to the best of our
      knowledge, only 24 cases have been reported to date. However, due to the
      different treatments and prognosis, the distinction between a primary ovarian
      tumour and metastasis of RCC is important. 

PMID- 24678364
TI  - Primary giant cell malignant fibrous histiocytoma-associated with renal calculus.
AB  - Malignant fibrous histiocytomas (MFH) are the most commonly seen soft tissue
      sarcomas in adults. It is rarely seen in some visceral organs. Kidneys are the
      parenchymal organs in which MFHs are most frequently seen. More than 50 cases of
      primary renal MFH have been reported. Among these cases, only 1 was reported as
      primary giant cell subtype in association with urolithiasis. This case report is
      the second such case with the these characteristics. 

PMID- 24678365
TI  - Transitional cell carcinoma arising in a calyceal cyst mimicking a cystic renal
      tumour.
AB  - Solitary renal cysts are relatively common. The occurrence of transitional cell
      carcinoma (TCC) in a renal cyst is rare. We present the case of a 59-year-old man
      with a medical history of viral hepatitis B. During a workup for his hepatitis, a
      computed tomography scan revealed a large cystic tumour in the upper region of
      the left kidney. A radical left nephrectomy was performed. Microscopic
      examination of the cystic tumour revealed a grade 2 TCC. The cyst was lined by
      transitional epithelium. This is a case of a TCC growing within a renal calyceal
      cyst. 

PMID- 24678366
TI  - Pudendal schwannoma: A case report and literature review.
AB  - Schwannomas are benign nerve sheath tumours most often associated with the
      cranial nerves and the peripheral nerve system of the neck and extremities.
      Pelvic schwannomas are rare, with only about 25 cases reported. We report the
      case of a 34-year-old man referred for worsening pain of 10 years duration
      involving the right testicle and right penile shaft. Magnetic resonance imaging
      discovered a well-circumscribed pelvic tumour of 3.2 * 2.8 * 3.2 cm. Considering
      the possible complications involved in exposing the pudendal nerve during
      surgical resection, we performed an extensive literature search to aid
      preoperative planning. The most commonly described surgical approach for pelvic
      schwannomas has been open median laparotomy with transperitoneal dissection. To
      our knowledge, pudendal schwannomas have never been described in the literature.
      However, after considering the location and characteristics of the tumour, we
      chose laparoscopy because it offers the advantages of better visualization of
      anatomical structures with minimal invasiveness and faster recovery. At the 3
      week follow-up, the patient described a significant decrease in pain and normal
      neurological and urological examinations. 

PMID- 24678367
TI  - Injury of the ileum during percutaneous nephrolithotomy in a pediatric patient.
AB  - Ileum injury during percutaneous nephrolithotomy (PCNL) is an extremely rare
      complication. We describe the successful management of an inadvertently injured
      ileum during subcostal PCNL in a 12-year-old boy. Mechanism of injury,
      presentation and management will be discussed. 

PMID- 24678368
TI  - Management of renocolic fistula following abdominal trauma from a Gunshot: Two
      cases reports.
AB  - The renocolic fistula is a rare entity. We report 2 cases of renocolic fistula
      penetrating an abdominal trauma from a gunshot. 

PMID- 24678369
TI  - Emphysematous cystitis: An atypical multi-organism presentation.
AB  - An 84-year-old diabetic women receiving in-hospital stroke management began
      suffering from vague lower abdominal pain, increased urge incontinence and gross
      hematuria. Physical examination revealed suprapubic tenderness and a tympanic
      bladder. A computed tomography confirmed a distended bladder with gas foci
      delineating the bladder wall. Microbiology revealed an atypical multi-organism
      presentation of Klebsiella pneumoniae and Enterococcus species. Emphysematous
      cystitis is characterized by air within the bladder wall often found in elderly
      diabetic females. Predominant organisms include Escherichia coli and Klebsiella
      pneumonia. Prompt treatment is essential in this potentially fatal condition. 

PMID- 24678370
TI  - The stone formation in the Memotherm urethral stent implantation area: Is it a
      rare complication?
AB  - Recurrent urethral stricture is one of the biggest problems in urology. Urethral
      stents as an alternative treatment has been used since 1985. The stone formation
      in the Memotherm (Angiomed) urethral stent implantation area is a rare
      complication. We report the case of a 67-year-old man who had a stone in the
      Memotherm urethral stent implantation area 6 years after his urethral stent
      surgery. 

PMID- 24678371
TI  - Computing maximum flow rates.

PMID- 24678372
TI  - How appropriate is circumcision?

PMID- 24678373
TI  - [Not Available].

PMID- 24678374
TI  - Exponential-family random graph models for valued networks.
AB  - Exponential-family random graph models (ERGMs) provide a principled and flexible
      way to model and simulate features common in social networks, such as
      propensities for homophily, mutuality, and friend-of-a-friend triad closure,
      through choice of model terms (sufficient statistics). However, those ERGMs
      modeling the more complex features have, to date, been limited to binary data:
      presence or absence of ties. Thus, analysis of valued networks, such as those
      where counts, measurements, or ranks are observed, has necessitated dichotomizing
      them, losing information and introducing biases. In this work, we generalize
      ERGMs to valued networks. Focusing on modeling counts, we formulate an ERGM for
      networks whose ties are counts and discuss issues that arise when moving beyond
      the binary case. We introduce model terms that generalize and model common social
      network features for such data and apply these methods to a network dataset whose
      values are counts of interactions.

PMID- 24678375
TI  - Congenital arhinia: A rare case.
AB  - PATIENT: Male, 4 months FINAL DIAGNOSIS: Congenital arhynia Symptoms: Absence of
      the nose Medication: - Clinical Procedure: - Specialty: Pediatrics and
      Noenatology * Genetics. OBJECTIVE: Congenital defects. BACKGROUND: Congenital
      nasal absence (arhinia) is an extremely rare malformation. Arhinia causes severe
      airway obstruction and poor feeding in the affected neonate. There is an
      association with other facial anomalies, especially defects of the eyes, ears,
      palate, and midline defects. CASE REPORT: A full-term boy was born via an
      uncomplicated vaginal delivery. The mother was 40 years old and had a normal
      pregnancy. The mother had 4 previous uncomplicated pregnancies. There was no
      history of drug use during pregnancy. CONCLUSIONS: Congenital arhinia is a rare
      defect of embryogenesis, often associated with other anomalies that significantly
      influence the immediate and long-term outcomes of the neonate. It is a
      potentially life-threatening condition and requires the presence of a highly
      skilled neonatal resuscitation team at the time of delivery. Parental counseling
      is vital and a multidisciplinary team approach is required to optimize neonatal
      outcome.

PMID- 24678376
TI  - The challenge of big data in public health: an opportunity for visual analytics.
AB  - Public health (PH) data can generally be characterized as big data. The efficient
      and effective use of this data determines the extent to which PH stakeholders can
      sufficiently address societal health concerns as they engage in a variety of work
      activities. As stakeholders interact with data, they engage in various cognitive
      activities such as analytical reasoning, decision-making, interpreting, and
      problem solving. Performing these activities with big data is a challenge for the
      unaided mind as stakeholders encounter obstacles relating to the data's volume,
      variety, velocity, and veracity. Such being the case, computer-based information
      tools are needed to support PH stakeholders. Unfortunately, while existing
      computational tools are beneficial in addressing certain work activities, they
      fall short in supporting cognitive activities that involve working with large,
      heterogeneous, and complex bodies of data. This paper presents visual analytics
      (VA) tools, a nascent category of computational tools that integrate data
      analytics with interactive visualizations, to facilitate the performance of
      cognitive activities involving big data. Historically, PH has lagged behind other
      sectors in embracing new computational technology. In this paper, we discuss the
      role that VA tools can play in addressing the challenges presented by big data.
      In doing so, we demonstrate the potential benefit of incorporating VA tools into
      PH practice, in addition to highlighting the need for further systematic and
      focused research. 

PMID- 24678377
TI  - Technical Description of the Distribute Project: A Community-based Syndromic
      Surveillance System Implementation.
AB  - This paper describes the design of a syndromic surveillance system implemented
      for community-based monitoring of influenza-like illness. The system began as
      collaboration between colleagues from state and large metropolitan area health
      jurisdictions, academic institutions, and the non-profit, International Society
      for Disease Surveillance. Over the six influenza seasons from 2006 to 2012, the
      system was automated and enhanced, with new features and infrastructure, and the
      resulting, reliable, enterprise grade system supported peer comparisons between
      44 state and local public health jurisdictions who voluntarily contributed
      summarized data on influenza-like illness and gastrointestinal syndromes. The
      system was unusual in that it addressed the needs of a widely distributed,
      voluntary, community engaged in real-time data integration to support operational
      public health. 

PMID- 24678378
TI  - Estimating increased electronic laboratory reporting volumes for meaningful use:
      ?implications for the public health workforce.
AB  - OBJECTIVE: To provide formulas for estimating notifiable disease reporting volume
      from 'meaningful use' electronic laboratory reporting (ELR). METHODS: We analyzed
      two years of comprehensive ELR reporting data from 15 metropolitan hospitals and
      laboratories. Report volumes were divided by population counts to derive
      generalizable estimators. RESULTS: Observed volume of notifiable disease reports
      in a metropolitan area were more than twice national averages. ELR volumes varied
      by institution type, bed count, and by the level of effort required of health
      department staff. CONCLUSIONS: Health departments may experience a significant
      increase in notifiable disease reporting following efforts to fulfill meaningful
      use requirements, resulting in increases in workload that may further strain
      public health resources. Volume estimators provide a method for predicting ELR
      transaction volumes, which may support administrative planning in health
      departments.

PMID- 24678379
TI  - The geographic distribution of mammography resources in Mississippi.
AB  - OBJECTIVE: To determine whether the availability of mammography resources
      affected breast cancer incidence rates, stage of disease at initial diagnosis,
      mortality rates and/or mortality-to-incidence ratios throughout Mississippi.
      METHODS: Mammography facilities were geocoded and the numbers of residents
      residing within a thirty minute drive of a mammography facility were calculated.
      Other data were extracted from the Mississippi Cancer Registry, the U.S. Census,
      and the Mississippi Behavioral Risk Factor Surveillance Survey (BRFSS). RESULTS &
      DISCUSSION: There were no statistically-significant differences between breast
      cancer incidence rates in Black versus White females in Mississippi; however,
      there were significant differences in the use of mammography, percentages of
      advanced-stage initial diagnoses, mortality rates, and mortality-to-incidence
      ratios, where Black females fared worse in each category. No statistically
      significant correlations were observed between breast cancer outcomes and the
      availability of mammography facilities. The use of mammography was negatively
      correlated with advanced stage of disease at initial diagnosis. By combining
      Black and White subsets, a correlation between mammography use and improved
      survival was detected; this was not apparent in either subset alone. There was
      also a correlation between breast cancer mortality-to-incidence ratios and the
      percentage of the population living below the poverty level. CONCLUSIONS: The
      accessibility and use of mammography resources has a greater impact on breast
      cancer in Mississippi than does the geographic resource distribution per se.
      Therefore, intensified mammography campaigns to reduce the percentage of advanced
      stage breast cancers initially diagnosed in Black women, especially in
      communities with high levels of poverty, are warranted in Mississippi.

PMID- 24678381
TI  - Android and ODK based data collection framework to aid in epidemiological
      analysis.
AB  - Periodic collection of field data, analysis and interpretation of data are key to
      a good healthcare service. This data is used by the subsequent decision makers to
      recognize preventive measures, provide timely support to the affected and to help
      measure the effects of their interventions. While the resources required for good
      disease surveillance and proactive healthcare are available more readily in
      developed countries, the lack of these in developing countries may compromise the
      quality of service provided. This combined with the critical nature of some
      diseases makes this an essential issue to be addressed. Taking advantage of the
      rapid growth of cell phone usage and related infrastructure in developed as well
      as developing countries, several systems have been established to address the
      gaps in data collection. Android, being an open sourced platform, has gained
      considerable popularity in this aspect. Open data kit is one such tool developed
      to aid in data collection. The aim of this paper is to present a prototype
      framework built using few such existing tools and technologies to address data
      collection for seasonal influenza, commonly referred to as the flu. 

PMID- 24678380
TI  - Experience of using information systems in public health practice: findings from
      a qualitative study.
AB  - OBJECTIVE: Data collection and management by local health departments (LHDs) is a
      complex endeavor, complicated by system level and organizational factors. The
      purpose of this study was to describe the processes and use of information
      systems (IS) utilized for data collection, management, and sharing by LHD
      employees. METHODS: We interviewed a purposive sample of 12 staff working in the
      key public health practice areas of communicable disease control, immunizations,
      and vital records from three LHDs in different states. Our interview questions
      addressed job descriptions, daily activities, and the use and perceptions of both
      data and IS in support of their work. A content analytic approach was used to
      derive themes and categories common across programmatic areas. RESULTS: Local
      public health involves the use of mix of state-supplied and locally implemented
      IS supported by paper records. Additionally, each LHD in this study used at least
      one shadow system to maintain a duplicate set of information. Experiences with IS
      functionality and the extent to which it supported work varied by programmatic
      area, but inefficiencies, challenges in generating reports, limited data
      accessibility, and workarounds were commonly reported. CONCLUSIONS: Current
      approaches to data management and sharing do not always support efficient public
      health practice or allow data to be used for organizational and community
      decision making. Many of the challenges to effective and efficient public health
      work were not solely technological. These findings suggest the need for
      interorganizational collaboration, increasing organizational capacity, workflow
      redesign, and end user training.

PMID- 24678382
TI  - Electronic health in ghana: current status and future prospects.
AB  - The health-care system in Ghana is similar to those in other developing countries
      and access to health services for remote communities is extremely limited. In
      July, 2010, the Government of Ghana launched the national e health strategy. A
      number of international organizations have initiated various pilot projects,
      including disseminating and collecting data, education initiatives and
      telemedicine. In addition, several institutions and organizations are dedicated
      to the promotion of e-health and a range of Web-based health consultancy services
      have begun. The main objective of this study is to provide an overview of eHealth
      activities in Ghana. It was a daunting task, not least because of the need to
      gather information on eHealth projects and initiatives in Ghana, as there is no
      existing repository of such information. Through literature search in Africa
      journals online, Hinari, Medline, Google.com, Journal of Telemedicine and e
      Health, Journal of Telemedicine and Telecare, Journal of Medical Internet
      Research and Interaction with eHealth experts, followed up with some of the
      authors' for directions to other projects, and following the references in some
      articles. A total of twenty-two (22) pilot projects have been identified in
      Ghana. Mobile devices in use range from PDAs to simple phones and smart phones.
      The key findings of this research are that there are about 22 eHealth project at
      various stages of implementation in Ghana. Some of these projects have wind up
      and others are still being implemented. Mobile devices in use range from PDAs to
      simple mobile phones and smart phones. Most of the projects have been donor
      initiated. Data collection started in March 2010 to June 2013. Although eHealth
      seems to have a limited role in Ghana at present, there is growing interest in
      the opportunities it may offer in terms of improving the delivery and access to
      services, especially in remote locations. Recommendations for further research
      are provided. 

PMID- 24678383
TI  - Lyme Disease in Maine: a Comparison of NEDSS Surveillance Data and Maine Health
      Data Organization Hospital Discharge data.
AB  - BACKGROUND: Lyme disease is the most commonly reported vector borne disease in
      the United States and is a major public health concern in Maine. Maine Center for
      Disease Control and Prevention (Maine CDC) monitors Lyme disease through a
      passive surveillance system. In order to validate the Lyme disease surveillance
      system, Maine CDC was interested in comparing trends with a secondary data
      source. Specifically, Maine CDC was interested in comparing trends by age group,
      gender, geography, and timelines. Also, because hospitalization due to Lyme
      disease is rare, this analysis provided an opportunity to look at the diagnosis
      codes used for Lyme disease visits. The purpose of this paper is to compare the
      data acquired through surveillance to a secondary data source in order to
      evaluate the completeness of the data and verify trends. METHODS: Surveillance
      data was extracted from Maine's NEDSS Base System for the years 2008 - 2011. Only
      confirmed and probable cases were included in data analysis. The Maine Health
      Data Organization (MHDO) collects information on all hospital inpatient and
      outpatient data visits and was used for this comparison. MHDO inpatient and
      outpatient hospital encounters with a diagnosis of 08881 in any diagnosis field
      were extracted from the full dataset from 2008 - 2011. RESULTS: Surveillance data
      showed the 5-14 year old age group had the highest rates of Lyme disease while
      outpatient data showed adults over the age of 45 to have the highest rates.
      Outpatient data showed a higher percentage of females with Lyme disease visits.
      Geographic trends did not match well between surveillance data and MHDO data
      which may be due to the hospital being used as proxy for the patient address.
      Timeliness trends were consistent between all sources, with the majority of Lyme
      disease occurring in the summer months of June, July and August. The majority of
      outpatient visits had Lyme disease listed as their primary diagnosis while the
      majority of inpatient visits had Lyme disease as a secondary or lower diagnosis.
      CONCLUSIONS: There were several limitations to this study including incomplete
      data, and the inability to differentiate between new and old Lyme diagnoses.
      There is reasonably good similarity in the trends of these two systems helping
      validate the usefulness of Maine's Lyme disease surveillance system. Many of the
      discrepancies warrant further investigation, and may lead to future opportunities
      for education or improvement in Lyme disease surveillance.

PMID- 24678384
TI  - mHealth: Using Mobile Technology to Support Healthcare.
AB  - Adherence to long-term therapy in outpatient setting is required to reduce the
      prevalence of chronic diseases such as HIV/AIDS, Diabetes, Tuberculosis and
      Malaria. This paper presents a mobile technology-based medical alert system for
      outpatient adherence in Nigeria. The system makes use of the SMS and voice
      features of mobile phones. The system has the potential of improving adherence to
      medication in outpatient setting by reminding patients of dosing schedules and
      attendance to scheduled appointments through SMS and voice calls. It will also
      inform patients of benefits and risks associated with adherence. Interventions
      aimed at improving adherence would provide significant positive return on
      investment through primary prevention (of risk factors) and secondary prevention
      of adverse health outcomes. 

PMID- 24678385
TI  - Citation-based Estimation of Scholarly Activity Among Domestic Academic Radiation
      Oncologists: Five-Year Update.
AB  - OBJECTIVE: To analyze up-to-date Hirsch index (h-index) data to estimate the
      scholarly productivity of academic radiation oncology faculty. METHODS:
      Bibliometric citation database searches were performed for radiation oncology
      faculty at domestic residency-training institutions. Outcomes analyzed included
      the number of manuscripts, number of citations, and h-index between 1996 and
      2012. Analyses of overall h-index rankings with stratification by academic
      ranking, gender, and departmental faculty size were performed. RESULTS: One
      thousand thirty-seven radiation oncologists from 87 programs were included.
      Overall, the mean h-index was 10.8. Among the top 10% by h-index, 38% were
      chairpersons, all were senior faculty, and 11% were women. As expected, higher h
      index was associated with higher academic ranking and senior faculty status.
      Recursive partitioning analysis revealed an h-index threshold of 20 (p <0.001) as
      an identified breakpoint between senior vs. junior faculty. Furthermore, h-index
      breakpoints of 12 (p <0.001) and 25 (p <0.001) were identified between assistant
      professor vs. associate professor, and associate professor vs. professor levels,
      respectively. Multivariate analysis identified higher academic ranking, male
      gender, and larger departmental faculty size as independent variables associated
      with higher h-index. CONCLUSION: The current results suggest an overall rise in
      scholarly citation metrics among domestic academic radiation oncologists, with a
      current mean h-index of 10.8, vs. 8.5 in 2008. Significant relationships exist
      between h-index and academic rank, gender, and departmental size. The results
      offer up-to-date benchmarks for evaluating academic radiation oncologist to the
      national average and potentially has utility in the process of appointment and
      promotion decisions.

PMID- 24678386
TI  - The influence of rotor type and centrifugation time on the yield and purity of
      extracellular vesicles.
AB  - BACKGROUND: Extracellular vesicles (EV), the collective term for vesicles
      released from cells, consist of vesicle species ranging in size from 30 nm to 5
      um in diameter. These vesicles are most commonly isolated by differential
      centrifugations, which pellets particles based on their differential movement
      through the liquid medium in which they are immersed. Multiple parameters,
      including the utilization of different rotor types, can influence the yield and
      purity of isolated vesicles; however, the understanding of how these factors
      affect is limited. MATERIALS AND METHODS: Here, we compare the influence of
      multiple centrifugation parameters, including the use of swinging bucket and
      fixed angle rotors, as well as different centrifugation times, for the isolation
      of the smallest EVs, "exosomes." In particular, we determine the yields of
      exosomal RNA and protein, as well as the nature of the isolated vesicles and
      possible protein contamination with methods such as electron microscopy, western
      blot and flow cytometry. RESULTS: Our results show that application of a specific
      g-force or rotation speed by itself does not predict the ability of pelleting
      exosomes, and that prolonged centrifugation times can achieve greater yields of
      exosomal RNA and protein, whereas very long centrifugation times result in
      excessive protein concentrations in the exosome pellet. CONCLUSION: In
      conclusion, rotor type, g-force and centrifugation times significantly influence
      exosome yield during centrifugation-based isolation procedures, and current
      commonly recommended isolation protocols may not be fully optimized for yield and
      purity of exosomes.

PMID- 24678387
TI  - The HIV Nef protein modulates cellular and exosomal miRNA profiles in human
      monocytic cells.
AB  - INTRODUCTION: The HIV Nef protein is a multifunctional virulence factor that
      perturbs intracellular membranes and signalling and is secreted into exosomes.
      While Nef-containing exosomes have a distinct proteomic profile, no comprehensive
      analysis of their miRNA cargo has been carried out. Since Nef functions as a
      viral suppressor of RNA interference and disturbs the distribution of RNA-induced
      silencing complex proteins between cells and exosomes, we hypothesized that it
      might also affect the export of miRNAs into exosomes. METHOD: Exosomes were
      purified from human monocytic U937 cells that stably expressed HIV-1 Nef. The RNA
      from cells and exosomes was profiled for 667 miRNAs using a Taqman Low Density
      Array. Selected miRNAs and their mRNA targets were validated by quantitative RT
      PCR. Bioinformatics analyses were used to identify targets and predict pathways.
      RESULTS: Nef expression affected a significant fraction of miRNAs in U937 cells.
      Our analysis showed 47 miRNAs to be selectively secreted into Nef exosomes and 2
      miRNAs to be selectively retained in Nef-expressing cells. The exosomal miRNAs
      were predicted to target several cellular genes in inflammatory cytokine and
      other pathways important for HIV pathogenesis, and an overwhelming majority had
      targets within the HIV genome. CONCLUSIONS: This is the first study to report
      miRnome analysis of HIV Nef expressing monocytes and exosomes. Our results
      demonstrate that Nef causes large-scale dysregulation of cellular miRNAs,
      including their secretion through exosomes. We suggest this to be a novel viral
      strategy to affect pathogenesis and to limit the effects of RNA interference on
      viral replication and persistence.

PMID- 24678388
TI  - Early and late complications related to central venous catheters in hematological
      malignancies: a retrospective analysis of 1102 patients.
AB  - Several severe complications may be associated with the use of central venous
      catheters (CVC). We retrospectively evaluated on a large cohort of patients the
      incidence of CVC-related early and late complications. From 7/99 to 12/2005, 1102
      CVC have been implanted at our Institution in 881 patients with hematological
      malignancies (142,202 total day number of implanted CVC). Early mechanic
      complications were 79 (7.2% - 0.55/1,000 days/CVC). Thirty-nine episodes of early
      infective complications (<1 week from CVC implant) occurred (3.5% - 0.3/1000
      days/CVC): furthermore, 187 episodes of CVC-related sepsis (17% - 1.3/1000
      days/CVC) were recorded. There were 29 episodes (2.6%) of symptomatic CVC-related
      thrombotic complications, with a median interval from CVC implant of 60 days
      (range 7 - 395). The rate of CVC withdrawal due to CVC-related complications was
      26%. The incidence of CVC-related complications in our series is in the range
      reported in the literature notwithstanding cytopenia often coexisting in
      hematological patients. 

PMID- 24678389
TI  - Prevention of beta Thalassemia in Northern Israel - a Cost-Benefit Analysis.
AB  - BACKGROUND: beta Thalassemia major is characterized by hemolytic anemia,
      ineffective erythropoiesis and hemosiderosis. About 4% of the world population
      carries a Thalassemia gene. Management includes blood transfusions and iron
      chelation. However, this treatment is costly, and population screening may be
      significantly more cost beneficial. PURPOSE: The purpose of the current study is
      to analyze the cost of running a prevention program for beta Thalassemia in
      Israel and to compare it to the actual expenses incurred by treating Thalassemia
      patients. METHODS: THREE COST PARAMETERS WERE ANALYZED AND COMPARED: the
      prevention program, routine treatment of patients and treatment of complications.
      An estimation of the expenses needed to treat patients who present with
      complications was calculated based on our ongoing experience in treating
      deteriorating patients. RESULTS AND CONCLUSIONS: The cost of preventing one
      affected newborn was $63,660 compared to $1,971,380 for treatment of a patient
      during 50 years (mean annual cost: $39,427). Thus, the prevention of 45 affected
      newborns over a ten year period represents a net saving of $88.5 million to the
      health budget. Even after deducting the cost of the prevention program
      ($413.795/year), the program still represents a benefit of $76 million over ten
      years. Each prevented case could pay the screening and prevention program for 4.6
      years.

PMID- 24678390
TI  - A Neglected Zoonosis in Albania: why Echinococcosis is Becoming a Surgeon's
      Exclusivity?
AB  - Echinococcosis is an endemic zoonosis in the Mediterranean area, with Albania
      interested actually to a level that is becoming a public health concern. Authors
      describe preliminary data from the only tertiary (university) medical facility of
      Albania, positioned in the capital of the country (Tirana), with 333 new cases
      diagnosed and treated during the period 2005 - 2011. Out of all these 333 new
      cases an impressive majority of 91% had a surgical treatment right from the first
      admission, rendering the disease almost a surgical exclusivity. Even more, 80% of
      all patients from the study group were hospitalized straightforwardly in surgical
      wards, with options of surgical intervention's percentages outrunning figures
      from other sources and authors of the same geographical area. Such a situation,
      together with a very important level of patients' origin from highly urbanized
      areas such as those of the capital, suggest the necessity of well-organized
      interventions, among which might be the mandatory notification of all human cases
      with Echinococcus infection. 

PMID- 24678391
TI  - Tacrolimus associated posterior reversible encephalopathy syndrome - a case
      series and review.
AB  - Tacrolimus is an immunosuppressive drug mainly used to lower the risk of
      transplant rejection in individuals who are post solid organ or hematopoietic
      transplantation. It is a macrolide which reduces peptidyl-propyl isomerase
      activity and inhibits calcineurin, thus inhibiting T-lymphocyte signal
      transduction and interleukin-2 (IL-2) transcription. It has been associated with
      Posterior Reversible Encephalopathy Syndrome (PRES), a disease of sudden onset
      that can present as a host of different symptoms, depending on the affected area
      of the brain. While infectious causes of encephalopathy must always be
      entertained, the differential diagnosis should also include PRES in the
      appropriate context. We report three cases of PRES in patients with acute myeloid
      leukemia (AML) placed on tacrolimus after receiving a bone marrow transplant
      (BMT). The focus of this review is to enhance clinical recognition of PRES as it
      is related to an adverse effect of Tacrolimus in the setting of hematopoietic
      transplantation. 

PMID- 24678392
TI  - Association of Mycobacterium Tuberculosis Lineages with IFN-gamma and TNF-alpha
      Gene Polymorphisms among Pulmonary Tuberculosis Patient.
AB  - The six major lineages of Mycobacterium tuberculosis [MTB] are found to be
      strongly associated with specific geographical outbreaks. But whether these
      bacterial lineages influence the host genetic polymorphism is uncertain. The
      present study was designed to evaluate the relevance of strain diversity and host
      genetic polymorphisms in susceptibility to pulmonary tuberculosis [PTB]. For this
      reason, single -nucleotide polymorphisms [SNPs] in interferon- gamma [IFN-gamma]
      receptor-1[G-611A], IFNG [G+ 2109A] and tumor necrosis factors [TNF-alpha] genes
      [at -238, 308,-857position] in patients [n=151] were analyzed and compared with
      controls [n=83]. The genetic diversity of M. tuberculosis isolates was performed
      using spacer oligonucleotide typing. Thereafter, the profile of IFN-gamma and TNF
      alpha allele frequency were investigated in each subtype of M.tuberculosis. The
      results showed C allele of TNF 857 and A allele of TNF 238 were more frequent in
      PTB cases [[TNF 857 C allele OR [CI95%] 0.6[0.4-0.9], p= 0.02] for TNF 238 A
      allele OR [CI95%] 5.5[3.4-9.0], p= 0.00]]. Similarly, G allele in IFNG+ 2109 A/G
      polymorphism were significantly more in patients than control subject[OR[CI95%]
      0.3; p< 0.05]. The major identified clinical isolates of M. tuberculosis were
      EAI[42; 27.8% ], Haarlem[ 31; 20.5% ], CAS [ 23;15.2% ], Beijing[14; 9.2%], and T
      [11; 7.2% ] lineages. No correction was observed between strains diversity and
      frequency of SNPs in studied PTB cases. In conclusions, we exclude the
      possibility of genetic mutation in IFN-gamma and TNF-alpha gene by different
      subtypes of M. tuberculosis. Although, our results supports a positive
      correlation between host SNPs and susceptibility to PTB. 

PMID- 24678393
TI  - Sorafenib Induced Hand Foot Skin Rash in FLT3 ITD Mutated Acute Myeloid Leukemia
      A Case Report and Review of Literature.
AB  - Sorafenib is a novel small molecule multiple kinase inhibitor which has been used
      for metastatic renal cancer, hepatocellular cancer. Sorafenib induced skin rash
      has been discussed as a side effect in trials in both, FLT3 wild type and mutated
      acute myeloid leukemia (AML), as monotherapy or as combination with other
      chemotherapeutic agents. We describe a patient with FLT 3 ITD mutated AML, who
      was started on adjunctive Sorafenib therapy. Skin reactions manifested as NCI
      Grade III palmoplantar erythrodysesthesia (PPE), requiring drug discontinuation.
      Several pathogenic mechanisms have been implicated in Sorafenib induced skin
      reactions, but none has been conclusively proven. While treatment options are
      varied for early stage skin reactions, drug discontinuation remains the only
      possible therapy presently for severe grade skin reaction. 

PMID- 24678394
TI  - Lymphomatoid granulomatosis of central nervous system and lung driven by epstein
      barr virus proliferation: successful treatment with rituximab-containing
      chemotherapy.
AB  - Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV)
      associated B-cell lymphoproliferative disorder. We report the case of a 41-year
      old man who presented with fever and respiratory symptoms. Computed tomography
      showed multiple nodules in both lung fields. Polymerase chain reaction (PCR)
      analysis for EBV was positive in bronchoalveolar lavage and biopsy of lung node
      yielded a diagnosis of LYG, grade III. Shortly after initiation of treatment with
      agressive chemotherapy, neurological deterioration appeared. Neuroimaging
      findings revealed hydrocephalus and PCR analysis of the cerebrospinal fluid (CSF)
      was positive for EBV. Treatment with intravenous rituximab led to rapid reduction
      of EBV load in CSF, along with clinical and radiological improvement. After
      completion of treatment with immunochemotherapy, an autologous stem cell
      transplantation was performed. Patient stays in remission 18 months after
      diagnosis. 

PMID- 24678395
TI  - Procalcitonin as a biomarker of bacterial infection in sickle cell vaso-occlusive
      crisis.
AB  - Sickle cell anaemia (SCA) patients with vaso-occlusive crisis (VOC) have signs of
      inflammation and it is often difficult to diagnose a bacterial infection in them.
      This study was undertaken to evaluate the role of serum procalcitonin (PCT) as a
      biomarker of bacterial infection in acute sickle cell vaso-occlusive crisis.
      Hundred homozygous SCA patients were studied at Sickle Cell Clinic and Molecular
      Biology Laboratory, V.S.S. Medical College, Burla, Odisha, India. All the
      patients were divided into three categories namely category-A (VOC/ACS with SIRS
      but without evidence of bacterial infection - 66 patients), category-B (VOC/ACS
      with SIRS and either proven or suspected bacterial infection - 24 patients) and
      category-C (SCA patients in steady state without VOC/ACS or SIRS - 10 patients).
      Complete blood count, C-reactive protein (CRP) estimation and PCT measurement
      were done in all the patients. There was no significant difference in TLC and CRP
      values between category-A and B. In category-A, the PCT level was <0.5 ng/mL in
      83.3% and 0.5-2 ng/mL in 16.7% of cases. In category-B, all the patients had PCT
      value >0.5 ng/mL with 87.5% of patients having >2 ng/mL. In category-C, PCT value
      was <0.5 ng/mL. PCT had a high sensitivity (100%) and negative predictive value
      (100%) for bacterial infection at a cutoff value of 0.5 ng/mL; whereas the
      specificity is excellent at a cut-off value of 2 ng/mL. SCA patients with VOC/ACS
      and SIRS having a PCT level of <0.5 ng/mL have a low probability of bacterial
      infection whereas PCT value of >2 ng/mL is indicative of bacterial infection
      necessitating early antimicrobial therapy. 

PMID- 24678396
TI  - Feasibility of collecting umbilical cord blood in jordan and the effect of
      maternal and neonatal factors on hematopoietic stem cell content.
AB  - BACKGROUND: Cord blood transplant is an accepted treatment for many malignant and
      non-malignant diseases. We sought to determine the feasibility of collecting cord
      blood in Jordan and the effect of maternal and fetal factors on the quality of
      the cord blood units. METHODS: A total of 124 cord blood units were collected,
      and 75 (60%) cord blood units were included in this analysis. Cord blood volume,
      total nucleated cell (TNC) count, cell viability and CD34(+) content were
      measured, and clonogenic assay was performed. RESULTS: The mean volume of the
      collected units was 68.9 ml (range 40-115) with mean nucleated cell count of 6.5
      x 10(8) (range 1-23.0). Our results showed a positive correlation between the
      volume of cord blood and TNC count (p=0.008), cell viability (p=0.001), CD34(+)
      content (p=0.034) and the length of the umbilical cord (p=0.011). In addition,
      our results showed an inverse relation between the Colony Forming Unit
      Granulocyte Macrophage (CFU-GM) concentration and the gestation duration
      (p=0.038). CONCLUSION: We conclude that it is feasible to collect cord blood
      units in Jordan with excellent TNC and CD34(+) cell content. The volume of cord
      blood collected was associated with higher TNC count and CD34(+) count. Efforts
      toward establishing public cord blood banks in our area are warranted.

PMID- 24678397
TI  - Azacitidine in chronic myelomonocytic leukemia: an effective and manageable
      approach.
AB  - Chronic myelomonocytic leukemia (CMML) is an uncommon neoplastic hematological
      disorder, typically affecting the elderly, and characterized by a marked clinical
      heterogeneity and a remarkable propensity for transformation into acute myeloid
      leukemia. Hypomethylating agents represent the most innovative management
      approach in this difficult setting. At our institution, between 2010 and 2012, we
      have treated with azacitidine 10 CMML patients with a median age of 75 (62-86)
      years. The overall response rate of 70% was achieved without remarkable
      toxicities; in particular, most therapy-induced side effects were managed on
      outpatient basis. With a median follow-up of 12,5 (2-27) months, 6 patients are
      alive, and 4 of them continue to receive the treatment; the median survival from
      the start of therapy was not reached. In conclusion, also in the light of our
      encouraging experience, azacitidine can offer new chances of treatment also in
      the difficult setting of elderly CMML. 

PMID- 24678398
TI  - Comment to the article "prevention of B thalassemia in northern Israel - a cost
      benefit analysis" by koren et Al.

PMID- 24678401
TI  - Retraction.

PMID- 24678399
TI  - The Price of Mercy: Comment to the Paper Entitled "Prevention of Beta Thalassemia
      In Northern Israel - A Cost-Benefit Analysis" by Koren et Al. recently published
      in Mediterranean Journal of Hematology and Infectious Diseases.

PMID- 24678403
TI  - Human adenovirus: Viral pathogen with increasing importance.
AB  - The aim of this review is to describe the biology of human adenovirus (HAdV), the
      clinical and epidemiological characteristics of adenoviral epidemic
      keratoconjunctivitis and to present a practical update on its diagnosis,
      treatment, and prophylaxis. There are two well-defined adenoviral
      keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis (EKC) and
      pharyngoconjunctival fever (PCF), which are caused by different HAdV serotypes.
      The exact incidence of adenoviral conjunctivitis is still poorly known. However,
      cases are more frequent during warmer months. The virus is endemic in the general
      population, and frequently causes severe disease in immunocompromised patients,
      especially the pediatric patients. Contagion is possible through direct contact
      or fomites, and the virus is extremely resistant to different physical and
      chemical agents. The clinical signs or symptoms of conjunctival infection are
      similar to any other conjunctivitis, with a higher incidence of pseudomembranes.
      In the cornea, adenoviral infection may lead to keratitis nummularis. Diagnosis
      is mainly clinical, but its etiology can be confirmed using cell cultures,
      antigen detection, polymerase chain reaction or immunochromatography. Multiple
      treatments have been tried for this disease, but none of them seem to be
      completely effective. Prevention is the most reliable and recommended strategy to
      control this contagious infection. 

PMID- 24678404
TI  - Development of anti-bovine IgA single chain variable fragment and its application
      in diagnosis of foot-and-mouth disease.
AB  - Recombinant antibody fragments like single chain variable fragments (scFvs)
      represent an attractive yet powerful alternative to immunoglobulins and hold
      great potential in the development of clinical diagnostic/therapeutic reagents.
      Structurally, scFvs are the smallest antibody fragments capable of retaining the
      antigen-binding capacity of whole antibodies and are composed of an
      immunoglobulin (Ig) variable light (VL) and variable heavy (VH) chain joined by a
      flexible polypeptide linker. In the present study, we constructed a scFv against
      bovine IgA from a hybridoma cell line IL-A71 that secretes a monoclonal antibody
      against bovine IgA using recombinant DNA technology. The scFv was expressed in
      Escherichia coli and purified using immobilized metal affinity chromatography
      (IMAC). The binding activity and specificity of the scFv was established by its
      non-reactivity toward other classes of immunoglobulins as determined by enzyme
      linked immunosorbent assay (ELISA) and immunoblot analysis. Kinetic measurement
      of the scFv indicated that the recombinant antibody fragment had an affinity in
      picomolar range toward purified IgA. Furthermore, the scFv was used to develop a
      sensitive ELISA for the detection of foot and mouth disease virus (FMDV) carrier
      animals. 

PMID- 24678405
TI  - Recombinant human antibody fragment against tetanus toxoid produced by phage
      display.
AB  - Phage display technology is a powerful in vitro method for the identification of
      specific monoclonal antibodies (antibody fragments) to an antigenic target and
      allows the rapid generation and selection of high affinity, fully human
      antibodies directed toward any disease target appropriate for antibody therapy.
      In the present study, we exploited the phage display technology for the selection
      of an antigen binding fragment (Fabs) toward tetanus toxoid using human naive
      phage antibody library constructed from peripheral blood lymphocytes of naive
      human donors. The phages displaying Fab were subjected to three rounds of bio
      panning with tetanus toxoid as antigen on a solid phase. The high affinity
      antibody fragments were expressed in HB2151 strain of Escherichia coli and
      purified by immobilized metal affinity chromatography. The binding activity and
      specificity of the antibody fragment was established by its reactivity toward
      tetanus toxoid and non-reactivity toward other related toxins as determined by
      enzyme-linked immunosorbent assay and immunoblot analysis. The selected Fab
      fragment forming the antigen-binding complexes with the toxoid in flocculation
      assay indicates that the Fab may have a potential neutralizing ability toward
      antigen. 

PMID- 24678406
TI  - Generation and characterization of neutralizing monoclonal antibodies against
      baculo-expressed HPV 16 VLPs.
AB  - Human papillomavirus (HPV) is the well-known second most cause of cervical cancer
      in women worldwide. According to the WHO survey, 70% of the total cervical
      cancers are associated with types HPV 16 and 18. Presently used prophylactic
      vaccine for HPV contains mainly capsid protein of L1 virus like particles (VLPs).
      Correct folding of VLPs and display of neutralizing epitopes are the major
      constraint for VLP-based vaccines. Further, monoclonal antibodies (mAbs) play a
      vital role in developing therapeutics and diagnostics. mAbs are also useful for
      the demonstration of VLP conformation, virus typing and product process
      assessment as well. In the present study, we have explored the usefulness of mAbs
      generated against sf-9 expressed HPV 16 VLPs demonstrated as type-specific and
      conformational dependent against HPV 16 VLPs by ELISA. High affinity and high
      pseudovirion neutralization titer of mAbs indicated their potential for the
      development of prophylactic vaccines for HPV. Also, the type-specific and
      conformational reactivity of the mAbs to HPV 16 VLPs in sf-9 cells by
      immunofluorescence assay proved their diagnostic potential. 

PMID- 24678402
TI  - Molecular diagnosis of sepsis: New aspects and recent developments.
AB  - By shortening the time to pathogen identification and allowing for detection of
      organisms missed by blood culture, new molecular methods may provide clinical
      benefits for the management of patients with sepsis. While a number of reviews on
      the diagnosis of sepsis have recently been published we here present up-to-date
      new developments including multiplex PCR, mass spectrometry and array techniques.
      We focus on those techniques that are commercially available and for which
      clinical studies have been performed and published. 

PMID- 24678408
TI  - High seroprevalence of Toxoplasma gondii infection in inmates: A case control
      study in Durango City, Mexico.
AB  - PURPOSE: The seroprevalence of infection with the parasite Toxoplasma gondii and
      the association with risk factors has not been determined in inmates. Through a
      case-control study, 166 inmates from a state correctional facility in Durango
      City, Mexico and 166 age- and gender-matched non-incarcerated subjects were
      examined for the presence of anti-T. gondii IgG and IgM antibodies using enzyme
      linked immunoassays. RESULTS: Seroprevalence of anti-T. gondii IgG antibodies was
      higher in inmates (35, 21.1%) than in controls (14, 8.4%) (OR = 2.90; 95% CI:
      1.43-5.94; P = 0.001). Anti-T. gondii IgM antibodies were detected in two (1.2%)
      inmates and in seven (4.2%) controls (P = 0.17). Multivariate analysis of socio
      demographic, incarceration, and behavioral characteristics of inmates revealed
      that T. gondii seropositivity was associated with being born out of Durango State
      (OR = 3.91; 95% CI: 1.29-11.79; P = 0.01). In addition, T. gondii seroprevalence
      was higher (P = 0.03) in inmates that had suffered from injuries (17/56: 30.4%)
      than those without such history (18/110: 16.4%). CONCLUSIONS: The seroprevalence
      of T. gondii infection in inmates in Durango City is higher than the
      seroprevalences found in the general population in the same city, indicating that
      inmates may represent a new risk group for T. gondii infection. Further research
      on T. gondii infection in inmates is needed.

PMID- 24678409
TI  - Congenital IL-12R1beta receptor deficiency and thrombophilia in a girl homozygous
      for an IL12RB1 mutation and compound heterozygous for MTFHR mutations: A case
      report and literature review.
AB  - Interleukin-12 (IL-12) plays an important role in the production of interferon
      gamma from T cells and natural killer cells and is essential for protection
      against intra-macrophagic pathogens such as Mycobacterium and Salmonella. Here,
      we describe a 16-year-old girl with homozygous mutation in exon 12 of the IL12RB1
      gene, which causes complete IL-12Rbeta1 deficiency in association with
      heterozygous mutation (C677T and A1298C) in the methylenetetrahydrofolate
      reductase gene. She presented with disseminated Mycobacterium tuberculosis
      complex infection, retroperitoneal fungal abscess and also thrombosis in the
      superior mesenteric-portal vein junction. This is the first case report of a
      primary immunodeficiency associated with a genetically determined venous
      thrombosis. 

PMID- 24678407
TI  - Spinal cord pathology in chronic experimental Toxoplasma gondii infection.
AB  - Infection with the protozoan Toxoplasma (T.) gondii causes chronic infection of
      the central nervous system and can lead to life-threatening encephalomyelitis in
      immunocompromised patients. While infection with T. gondii has long time been
      considered asymptomatic in immunocompetent hosts, this view is challenged by
      recent reports describing links between seropositivity and behavioral
      alterations. However, past and current researches are mainly focused on the brain
      during Toxoplasma encephalitis, neglecting the spinal cord as a key structure
      conveying brain signals into motion. Therefore, our study aimed to fill the gap
      and describes the spinal cord pathology in an experimental murine model of
      toxoplasmosis. In the spinal cord, we found distinct histopathological changes,
      inflammatory foci and T. gondii cysts similar to the brain. Furthermore, the
      recruitment of immune cells from the periphery was detected. Moreover, resident
      microglia as well as recruited monocytes displayed an increased MHC classes I and
      II expression. Additionally, the expression of pro- and anti-inflammatory
      cytokines was enhanced in the brain as well as in the spinal cord. In summary,
      the pathology observed in the spinal cord was similar to the previously described
      changes in the brain during the infection. This study provides the first detailed
      description of histopathological and immunological alterations due to
      experimental T. gondii induced myelitis in mice. Thus, our comparison raises
      awareness of the importance of the spinal cord in chronic T. gondii infection. 

PMID- 24678411
TI  - Methotrexate for the treatment of thyroid eye disease.
AB  - Background/Aim. To evaluate the efficacy of methotrexate for the treatment of
      thyroid eye disease (TED). Methods. 36 consecutive patients with active TED,
      previously treated with corticosteroids but stopped due to the occurrence of side
      effects, were commenced on methotrexate therapy. Two different weekly doses were
      administered depending on the weight of the patient (7.5 mg or 10 mg). Clinical
      activity score (7-CAS), visual acuity (VA), ocular motility, exophthalmos, and
      eyelid position were retrospectively evaluated at 3, 6, and 12 months and
      compared with baseline data. Results. There was a statistically significant
      improvement in 7-CAS at 3, 6, and 12 months after treatment (P < 0.0001). There
      was no significant change in visual acuity. Ocular motility disturbances improved
      at 6 and 12 months (P < 0.001). There was no significant change in exophthalmos
      (mean 24 mm, SD 3 mm) or eyelid position (marginal reflex distance mean 6 mm, SD
      1.5 mm) during the follow-up period. No side effects were registered.
      Conclusions. Methotrexate therapy is effective in reducing CAS and ocular
      motility disturbances. No significant improvement in proptosis or eyelid
      retraction should be expected from this treatment. Eventually, it might be
      considered a suitable alternative treatment in TED for patients who cannot
      tolerate steroids. 

PMID- 24678412
TI  - Gender differences in birdshot chorioretinopathy and the white dot syndromes: do
      they exist?
AB  - Inflammatory conditions that affect the posterior pole are diverse. Specifically,
      birdshot chorioretinopathy and the white dot syndromes present with multiple
      white dots in the fundus. These diseases appear to affect similar age groups but
      there is question as to whether or not a difference exists between the genders.
      This review summarizes the current studies on birdshot chorioretinopathy and the
      white dot syndromes as they are related to gender, exploring the differences, if
      any, which may exist between prevalence, clinical presentation, and treatment
      response for these diseases. Though the specific etiology of these diseases
      remains unclear, future treatments may be guided as to how these diseases affect
      the sexes differently. 

PMID- 24678413
TI  - Pulse-Wave Analysis of Optic Nerve Head Circulation Is Significantly Correlated
      with Kidney Function in Patients with and without Chronic Kidney Disease.
AB  - Aim. To determine whether there is a significant correlation between the optic
      nerve head (ONH) circulation determined by laser speckle flowgraphy (LSFG) and
      kidney function. Materials. Seventy-one subjects were investigated. The estimated
      glomerular filtration rate (GFR) and serum creatinine, cystatin C, and urinary
      albumin excretion were measured. The ONH circulation was determined by an
      analysis of the pulse wave of LSFG, and this parameter was named blowout time
      (BOT). Chronic kidney disease (CKD) was defined to be present when the estimated
      GFR was <60 mL/min per 1.73 m(2). Pearson's correlation coefficients were used to
      determine the relationship between the BOT and the kidney function. We also
      examined whether there were significant differences in all parameters in patients
      with and without CKD. Results. BOT was significantly correlated with the level of
      creatinine (r = -0.24, P = 0.04), the estimated GFR (r = 0.42, P = 0.0003),
      cystatin C (r = -0.29, P = 0.01), and urinary albumin excretion (r = -0.29, P =
      0.01). The BOT level in subjects with CKD was significantly lower than that in
      subjects without CKD (P = 0.002). Conclusion. BOT in ONH by LSFG can detect the
      organ damage such as kidney dysfunction, CKD. 

PMID- 24678414
TI  - Sodium intake, dietary knowledge, and illness perceptions of controlled and
      uncontrolled rural hypertensive patients.
AB  - Introduction and Objectives. Nutritional knowledge of the patients is important
      in dietary adherence. This study aimed to determine the relationship between
      illness perceptions and nutritional knowledge with the amounts of sodium intake
      among rural hypertensive patients. Methods. In a cross-sectional study, 671
      hypertensive patients were selected in a multistage random sampling from the
      rural areas of Ardabil city, Iran, in 2013. Data were collected using a
      questionnaire consisting of four sections and were analyzed using Pearson
      correlation and multiple linear regressions by SPSS-18. Results. The mean of
      sodium intake in the uncontrolled hypertensive patients was 3599 +/- 258 mg/day
      and significantly greater than controlled group (2654 +/- 540 mg/day) (P <
      0.001). Knowledge and illness perceptions could predict 47.2% of the variation in
      sodium intake of uncontrolled group. A significant negative relationship was
      found between knowledge and illness perceptions of uncontrolled hypertensive
      patients with dietary sodium intake (r = -0.66, P < 0.001 and r = -0.65, P <
      0.001, resp.). Conclusion. Considering the fact that patients' nutritional
      knowledge and illness perceptions could highly predict their sodium intake, the
      importance of paying more attention to improve patients' information and
      perceptions about hypertension is undeniable, especially among the uncontrolled
      hypertensive patients. 

PMID- 24678416
TI  - The burden of blood-pressure-related cardiovascular mortality in Mexico.
AB  - This study shows that in Mexico, a country at an advanced stage in the
      epidemiologic transition, with the national burden of disease dominated by
      noncommunicable diseases, elevated blood pressure is a major clinical and public
      health problem. 31.7% of the Mexican individuals aged 50 and over had systolic
      hypertension, and 47.3% were at systolic prehypertensive levels. Also,
      approximately half of all cardiovascular deaths that occurred annually in the
      population of Mexico aged >=50 years are attributable to above optimal levels of
      systolic blood pressure. We think these estimates may help order health
      priorities in Mexico (and other middle-income countries) at a time when the costs
      of medical care take a considerable share of the gross national product in most
      countries. 

PMID- 24678417
TI  - Participation of 5-HT and AT1 Receptors within the Rostral Ventrolateral Medulla
      in the Maintenance of Hypertension in the Goldblatt 1 Kidney-1 Clip Model.
AB  - The hypothesis that changes in neurotransmission within the rostral ventrolateral
      medulla (RVLM) are important to maintain the high blood pressure (BP) was tested
      in Goldblatt one kidney-one clip hypertension model (1K-1C). Male Wistar rats
      were anesthetized (urethane 1.2 g/kg, i.v.), and the effects of bilateral
      microinjections into the RVLM of the following drugs were measured in 1K-1C or
      control groups: glutamate (0.1 mol/L, 100 nL) and its antagonist kynurenic acid
      (0.02 mol/L, 100 nL), the angiotensin AT1 receptor antagonist candesartan (0.01
      mol/L, 100 nL), and the nonselective 5-HT receptor antagonist methiothepin (0.06
      mol/L, 100 nL). Experiments in 1K-1C rats were performed 6 weeks after surgery.
      In anesthetized rats glutamate response was larger in hypertensive than in
      normotensive rats (H: Delta67 +/- 6.5; N: Delta43 +/- 3.54 mmHg). In contrast,
      kynurenic acid microinjection into the RVLM did not cause any change in BP in
      either group. The blockade of either AT1 or 5-HT receptors within the RVLM
      decreased BP only in 1K-1C rats. A largest depressor response was caused by 5-HT
      receptor blockade. The data suggest that 5-HT and AT1 receptors act tonically to
      drive RVLM in 1K-1C rats, and these actions within RVLM contribute to the
      pathogenesis of this model of hypertension. 

PMID- 24678415
TI  - Cardiovascular Risk Factors and Chronic Kidney Disease-FGF23: A Key Molecule in
      the Cardiovascular Disease.
AB  - Patients with chronic kidney disease (CKD) are at increased risk of mortality,
      mainly from cardiovascular disease. Moreover, abnormal mineral and bone
      metabolism, the so-called CKD-mineral and bone disorder (MBD), occurs from early
      stages of CKD. This CKD-MBD presents a strong cardiovascular risk for CKD
      patients. Discovery of fibroblast growth factor 23 (FGF23) has altered our
      understanding of CKD-MBD and has revealed more complex cross-talk and endocrine
      feedback loops between the kidney, parathyroid gland, intestines, and bone.
      During the past decade, reports of clinical studies have described the
      association between FGF23 and cardiovascular risks, left ventricular hypertrophy,
      and vascular calcification. Recent translational reports have described the
      existence of FGF23-Klotho axis in the vasculature and the causative effect of
      FGF23 on cardiovascular disease. These findings suggest FGF23 as a promising
      target for novel therapeutic approaches to improve clinical outcomes of CKD
      patients. 

PMID- 24678418
TI  - Lifestyle factors in hypertension drug research: systematic analysis of articles
      in a leading cochrane report.
AB  - Established standards for first-line hypertension management include lifestyle
      modification and behavior change. The degree to which and how lifestyle
      modification is systematically integrated into studies of first-line drug
      management for hypertension is of methodological and clinical relevance. This
      study systematically reviewed the methodology of articles from a recent Cochrane
      review that had been designed to inform first-line medical treatment of
      hypertension and was representative of high quality established clinical trials
      in the field. Source articles (n = 34) were systematically reviewed for lifestyle
      interventions including smoking cessation, diet, weight loss, physical activity
      and exercise, stress reduction, and moderate alcohol consumption. 54% of articles
      did not mention lifestyle modification; 46% contained nonspecific descriptions of
      interventions. We contend that hypertension management research trials (including
      drug studies) need to elucidate the benefits and risks of drug-lifestyle
      interaction, to support the priority of lifestyle modification, and that
      lifestyle modification, rather than drugs, is seen by patients and the public as
      a priority for health professionals. The inclusion of lifestyle modification
      strategies in research designs for hypertension drug trials could enhance current
      research, from trial efficacy to clinical outcome effectiveness, and align
      hypertension best practices of a range of health professionals with evidence
      based knowledge translation. 

PMID- 24678420
TI  - The impact of insurance and a usual source of care on emergency department use in
      the United States.
AB  - Background. Finding a usual source of care (USC) is difficult for certain
      populations. This analysis determines how insurance type and having a USC affect
      the settings in which patients seek care. Methods. In this cross-sectional study
      of the 2000-2011 Medical Expenditure Panel Surveys, we assessed the percentage of
      low-income persons with half or more of their ambulatory visits to the emergency
      department (ED). Respondents were stratified based on insurance type and presence
      of a USC. Results. In 2011, among Medicaid enrollees without USCs, 21.6% had half
      or more of their ambulatory visits to EDs compared to 8.1% for those with USCs.
      Among the uninsured without USCs, 24.1% went to an ED for half or more of their
      ambulatory visits compared to 8.8% for those with USCs in 2011. Among the
      privately insured without USCs, 7.8% went to an ED for half or more of their
      ambulatory visits compared to 5.0% for those with USCs in 2011. These differences
      remained in multivariate analyses. Conclusions. Those who lack USCs, particularly
      the uninsured and Medicaid enrollees, are more likely to rely on EDs. 

PMID- 24678419
TI  - Glucosamine for osteoarthritis: biological effects, clinical efficacy, and safety
      on glucose metabolism.
AB  - Osteoarthritis is a chronic degenerative disorder that currently represents one
      of the main causes of disability within the elderly population and an important
      presenting complaint overall. The pathophysiologic basis of osteoarthritis
      entails a complex group of interactions among biochemical and mechanical factors
      that have been better characterized in light of a recent spike in research on the
      subject. This has led to an ongoing search for ideal therapeutic management
      schemes for these patients, where glucosamine is one of the most frequently used
      alternatives worldwide due to their chondroprotective properties and their long
      term effects. Its use in the treatment of osteoarthritis is well established; yet
      despite being considered effective by many research groups, controversy surrounds
      their true effectiveness. This situation stems from several methodological
      aspects which hinder appropriate data analysis and comparison in this context,
      particularly regarding objectives and target variables. Similar difficulties
      surround the assessment of the potential ability of glucosamine formulations to
      alter glucose metabolism. Nevertheless, evidence supporting diabetogenesis by
      glucosamine remains scarce in humans, and to date, this association should be
      considered only a theoretical possibility. 

PMID- 24678421
TI  - A colorimetric method for monitoring tryptic digestion prior to shotgun
      proteomics.
AB  - Tryptic digestion is an important preanalytical step in shotgun proteomics
      because inadequate or excessive digestion can result in a failed or incomplete
      experiment. Unfortunately, this step is not routinely monitored before mass
      spectrometry because methods available for protein digestion monitoring either
      are time/sample consuming or require expensive equipment. To determine if a
      colorimetric method (ProDM Kit) can be used to identify the extent of tryptic
      digestion that yields the best proteomics outcome, plasma and serum digested for
      8 h and 24 h were screened with ProDM, Bioanalyzer, and LC/MS/MS, and the effect
      of digestion on the number of proteins identified and sequence coverage was
      compared. About 6% and 16% less proteins were identified when >50% of proteins
      were digested in plasma and serum, respectively, compared to when ~46% of
      proteins were digested. Average sequence coverage for albumin, haptoglobin, and
      serotransferrin after 2 h, 8 h, and 24 h digestion was 52%, 45%, and 45% for
      serum and 54%, 47%, and 42% for plasma, respectively. This paper reiterates the
      importance of optimizing the tryptic digestion step and demonstrates the extent
      to which ProDM can be used to monitor and standardize protein digestion to
      achieve better proteomics outcomes. 

PMID- 24678422
TI  - Following up on clinical recommendations in transitions from hospital to nursing
      home.
AB  - Following up on recommendations made at the time of a hospital discharge is
      important to patient safety. While data is lacking, specifically around the
      transition of patient to nursing home, it has been postulated that missed items
      such as laboratory tests may result in adverse patient outcomes. To determine the
      extent of this problem, a retrospective cohort study of subjects discharged from
      an academic medical center and admitted to nursing homes (NH) was followed to
      determine the type of discharge recommendations and the rate of completion. In
      addition, for the purpose of generalizability, the 30-day hospital readmission
      rate was calculated. 152 recommendations were made on 51 subjects. Almost a
      quarter of the recommendations made by the hospital discharging team were not
      acted upon. Furthermore, for the majority of those recommendations that were not
      acted upon, a reason could not be determined. In concert with national data, 20%
      of the subjects returned to the hospital within 30 days. Further investigation is
      warranted to determine if an association exists between missed recommendations
      and hospital readmission from the nursing home setting. 

PMID- 24678423
TI  - Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in
      Patients with Nonalcoholic Fatty Liver.
AB  - Background & Aims. Hepatocyte apoptosis may play a role in progression of
      nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms
      responsible for liver damage. The aim was to determine the association of
      oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte
      apoptosis. Methods. Steatosis severity was defined according to Hamaguchi's
      echographic criteria in 209 patients with nonalcoholic fatty liver. Serum
      cytokeratin-18, urinary 8-iso-prostaglandin F2 alpha , soluble NOX2-derived
      peptide, and adiponectin were measured. Results. Serum cytokeratin-18
      progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176
      (140/190) and 180 (169.5/192.5) MU IU/mL in mild, moderate, and severe steatosis,
      respectively; P < 0.01). After stratification by cytokeratin-18 tertiles, a
      significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso
      PGF2 alpha , soluble NOX2-derived peptide, and of the prevalence of diabetes and
      severe steatosis was found, while HDL-cholesterol and adiponectin progressively
      decreased. A positive correlation between cytokeratin-18 and body mass index,
      HOMA-IR, Hamaguchi's score, urinary 8-iso-PGF2 alpha , and soluble NOX2-derived
      peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and
      adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived
      peptide were independent predictors of serum cytokeratin-18 levels (adjusted R
      (2) = 0.36). Conclusion. We support an association between oxidative stress and
      severity of liver damage in patients with nonalcoholic fatty liver. 

PMID- 24678424
TI  - Analysis of Photosynthetic Characteristics and UV-B Absorbing Compounds in Mung
      Bean Using UV-B and Red LED Radiation.
AB  - Mung bean has been reported to have antioxidant, antidiabetic, anti-inflammatory,
      and antitumor activities. Various factors have important effects on the types and
      contents of plant chemical components. In order to study quality of mung bean
      from different light sources, mung bean seedlings were exposed to red light
      emitting diodes (LEDs) and ultraviolet-B (UV-B). Changes in the growth
      parameters, photosynthetic characteristics, the concentrations of chlorophyll a
      and chlorophyll b and the content of UV-B absorbing compounds were measured. The
      results showed that photosynthetic characteristics and chlorophyll a and
      chlorophyll b concentrations were enhanced by red LEDs. The concentrations of UV
      B absorbing compounds were enhanced by UV-B on the 20th day, while photosynthetic
      characteristics, plant length, and the concentrations of chlorophyll a and
      chlorophyll b were reduced by UV-B on the 40th day; at the same time the values
      of the stem diameter, plant fresh weight, dry weight, and the concentrations of
      UV-B absorbing compounds were enhanced. It is suggested that red LEDs promote the
      elongation of plant root growth and photosynthetic characteristics, while UV-B
      promotes horizontal growth of stems and the synthesis of UV-B absorbing
      compounds. 

PMID- 24678425
TI  - Simple and sensitive analysis of blonanserin and blonanserin C in human plasma by
      liquid chromatography tandem mass spectrometry and its application.
AB  - A highly sensitive, simple, and rapid liquid chromatography tandem mass
      spectrometry method to simultaneously determine blonanserin and blonanserin C in
      human plasma with AD-5332 as internal standard (IS) was established. A simple
      direct protein precipitation method was used for the sample pretreatment, and
      chromatographic separation was performed on a Waters XBridge C8 (4.6 * 150 mm,
      3.5  MU m) column. The mobile phase consists of a mixture of 10 mM ammonium
      formate and 0.1% formic acid in water (A) and 0.1% formic acid in methanol (B).
      To quantify blonanserin, blonanserin C, and IS, multiple reaction monitoring
      (MRM) was performed in positive ESI mode. The calibration curve was linear in the
      concentration range of 0.012-5.78 ng.mL(-1) for blonanserin and 0.023-11.57
      ng.mL(-1) for blonanserin C (r (2) > 0.9990). The intra- and interday precision
      of three quality control (QC) levels in plasma were less than 7.5%. Finally, the
      current simple, sensitive, and accurate LC-MS/MS method was successfully applied
      to investigate the pharmacokinetics of blonanserin and blonanserin C in healthy
      Chinese volunteers. 

PMID- 24678427
TI  - Prototyping of cerebral vasculature physical models.
AB  - BACKGROUND: Prototyping of cerebral vasculature models through stereolithographic
      methods have the ability to accurately depict the 3D structures of complicated
      aneurysms with high accuracy. We describe the method to manufacture such a model
      and review some of its uses in the context of treatment planning, research, and
      surgical training. METHODS: We prospectively used the data from the rotational
      angiography of a 40-year-old female who presented with an unruptured right
      paraclinoid aneurysm. The 3D virtual model was then converted to a physical life
      sized model. RESULTS: The model constructed was shown to be a very accurate
      depiction of the aneurysm and its associated vasculature. It was found to be
      useful, among other things, for surgical training and as a patient education
      tool. CONCLUSION: With improving and more widespread printing options, these
      models have the potential to become an important part of research and training
      modalities.

PMID- 24678426
TI  - NF-kappaB and Rheumatoid Arthritis: Will Understanding Genetic Risk Lead to a
      Therapeutic Reward?
AB  - NF-kappaB has long been known to play an important role in autoimmune diseases
      such as rheumatoid arthritis (RA). Indeed, as our understanding of how NF-kappaB
      is utilized has increased, we have been hard put to find a process not associated
      with this transcription factor family in some way. However, new data originating,
      in part, from genome-wide association studies have demonstrated that very
      specific alterations in components of the NF-kappaB pathway are sufficient to
      confer increased risk of developing disease. Here we review the data which have
      identified specific components of the NF-kappaB pathway, and consider what is
      known of their mechanisms of action and how these mechanisms might play into the
      disease process. In addition, the use of genetic information to predict RA is
      considered.

PMID- 24678428
TI  - External lumbar drain: A pragmatic test for prediction of shunt outcomes in
      idiopathic normal pressure hydrocephalus.
AB  - BACKGROUND: The consensus on most reliable supplemental test to predict the shunt
      responsiveness in patients with idiopathic normal pressure hydrocephalus (iNPH)
      is lacking. The aim of this study is to discuss the utility of external lumbar
      drain (ELD) in evaluation of shunt responsiveness for iNPH patients. METHODS: A
      retrospective review of 66 patients with iNPH was conducted. All patients
      underwent 4-day ELD trial. ELD-positive patients were offered
      ventriculoperitoneal shunt (VPS) surgery. The primary outcome evaluation
      parameters were gait and mini mental status examination (MMSE) assessment. The
      family and patient perception of improvement was accounted for in the outcome
      evaluation. RESULTS: There were 38 male and 28 female with mean age of 74 years
      (range 45-88 years). ELD trial was positive in 86% (57/66) of patients. No major
      complications were encountered with the ELD trial. A total of 60 patients (57 ELD
      positive, 3 ELD-negative) underwent VPS insertion. The negative ELD trial (P =
      0.006) was associated with poor outcomes following shunt insertion. The positive
      ELD trial predicted shunt responsiveness in 96% patients (P < 0.0001, OR = 96.2,
      CI = 11.6-795.3). A receiver operating characteristic (ROC) curve analysis
      revealed that the ELD trial is reasonably accurate in differentiating shunt
      responder from non-responder in iNPH patients (area under curve = 0.8 +/- 0.14, P
      = 0.02, CI = 0.52-1.0). The mean follow-up period was 12-months (range 0.3-3
      years). The significant overall improvement after VPS was seen in 92% (55/60).
      The improvement was sustained in 76% of patients at mean 3-year follow-up. The
      number of comorbid conditions (P = 0.034, OR = 4.15, CI = 1.2-9.04), and a
      history of cerebrovascular accident (CVA) (P = 0.035, OR = 4.4, CI = 1.9-14.6)
      were the predictors of poor outcome following shunt surgery. CONCLUSION: The
      positive ELD test predicted shunt responsiveness in 96% of patients. With
      adequate technique, maximal results with minimal complications can be
      anticipated. The number of comorbidities, history of CVA and negative ELD test
      were significantly associated with poor shunt outcomes.

PMID- 24678429
TI  - Hemangiopericytoma of the foramen magnum in a pregnant patient: A case report and
      literature review.
AB  - BACKGROUND: The presentation of intracranial hemangiopericytomas is very rare,
      and only one case of a hemangiopericytoma during pregnancy has been reported in
      the literature. The management of these lesions poses a great challenge to the
      neurosurgeon, since the physiological and hormonal changes of pregnancy can
      exacerbate the symptoms of this highly vascularized neoplasm and pose different
      risks to both the mother and the fetus. We report the case of a patient who had
      sudden onset of intracranial hypertension at the ninth week of gestation due to a
      hemangiopericytoma of the foramen magnum and review the literature in this
      regard. CASE DESCRIPTION: A 23-year-old female who presented with signs and
      symptoms of intracranial hypertension at the ninth week of gestation was
      initially thought to have hyperemesis gravidarum. Because her symptoms persisted,
      she was found to have intracranial hypertension due to a tumor in the foramen
      magnum. She was treated by means of derivative surgery to allow for her pregnancy
      to progress beyond the first trimester, and at the 22(nd) week of gestation she
      underwent a sub-occipital craniotomy with partial tumor removal. Pathology was
      consistent with hemangiopericytoma. Both the mother and the fetus had positive
      outcomes. CONCLUSIONS: To our knowledge, this is the second intracranial
      hemangiopericytoma presenting during pregnancy to be reported in the literature,
      and it is the first one of its kind to be located in the foramen magnum and
      causing severe intracranial hypertension.

PMID- 24678430
TI  - The "extended" endoscopic endonasal approach for the removal of a mixed
      intrasuprasellar germinoma: Technical case report.
AB  - BACKGROUND: Intracranial germ cell tumors (GCTs) represent less than 5% of
      pediatric brain tumors. Neurosurgical treatment remains essential in the
      management of patients with intracranial nongerminomatous GCT. CASE DESCRIPTION:
      A 12-year-old girl presented with clinical features of neurohypophyseal
      dysfunction and rapidly progressive visual worsening. Magnetic resonance imaging
      (MRI) showed a lesion arising from the sella with a significant suprasellar
      component, compressing the optic chiasm and extending into the third ventricle.
      The tumor was removed via an endoscopic endonasal transtuberculum-transplanum
      approach and the histology revealed a mixed germinoma. In the postoperative
      course, a conspicuous improvement of visual function was observed; an early
      postoperative MRI showed near-total removal of the lesion. The patient was
      referred to pediatric oncologist for the adjunctive chemotherapy and
      radiotherapy. CONCLUSIONS: The management of primary intracranial sellar and
      suprasellar germinomas still remains controversial. With this report we
      highlighted another possible surgical option among therapeutic strategies for
      these highly malignant tumors.

PMID- 24678431
TI  - Successful excision of a pontomesencephalic cavernoma through anterior
      subtemporal route without mapping: Anatomical landmarks as a road map.

PMID- 24678432
TI  - Bilateral telovelar approach: A safe route revisited for resections of various
      large fourth ventricle tumors.
AB  - BACKGROUND: Tumors located in the posterior fossa and especially in the middle
      and upper fourth ventricle are comparatively rare and technically very
      challenging. For some lesions, the telovelar approach has been shown to be a
      suitable approach. The unilateral approach is sufficient in most cases of small
      lesions. However, large fourth ventricle tumors are more problematic since they
      distort the normal anatomy with both vermis and cerebellar peduncles thinned and
      stretched out. This puts the patient at increased risk for a neurological
      deficit, which is minimized with a bilateral telovelar approach. By illustrating
      the adequacy of this technique, we emphasize the suitability of a rather unusual
      bilateral approach, which will provide excellent panoramic visualization of
      entire fourth ventricle and thus avoids complications usually associated with
      resections of large fourth ventricle tumors. CASE DESCRIPTION: Here we present
      three cases of benign intraventricular tumors (meningioma, solitary fibrous tumor
      and ependymoma) in patients with site specific symptoms from local mass effect.
      Typical symptoms of posterior fossa lesions were present preoperatively and
      resolved after surgery. The bilateral telovelar approach was used to remove these
      tumors completely and the pertinent intraoperative steps are described for each
      case. All three patients had excellent postoperative outcome and could be
      discharged after short hospital stays. CONCLUSION: The different pathological
      entities could be completely resected without added neurological deficit
      employing a bilateral approach. In cases of large or giant fourth ventricle
      tumors, the bilateral telovelar approach provides excellent intraoperative
      visibility allowing complete excision of extensive tumors with minimal morbidity.

PMID- 24678433
TI  - Unintended thermal injuries from radiofrequency ablation: organ protection with
      an angioplasty balloon catheter in an animal model.
AB  - OBJECTIVES: The aim of this study was to investigate a novel approach of using a
      balloon catheter as a protective device to separate liver from the diaphragm or
      nearby bowel during radiofrequency ablation (RFA) of hepatic dome tumors in an
      animal model. MATERIALS AND METHODS: All experimental procedures were approved by
      animal Institutional Review Board. Using a 3 cm RF needle electrode, 70 hepatic
      ablation zones were created using ultrasound in 7 pigs. 50 lesions were created
      using balloon interposition between liver and diaphragm; 20 lesions were created
      using the balloon device interposed posteriorly between liver and bowel.
      Additional 21 control lesions were performed. Animals were sacrificed
      immediately; diaphragm and bowel were then visually inspected and sectioned.
      Diaphragmatic and bowel injury was then classified according to the depth of
      thickness. RESULTS: Control lesions caused full thickness injury, either to
      diaphragm or bowel. During ablation of lesions with balloon interposition, there
      was significantly less diaphragmatic injury, P < 0.001 and less bowel injury, P <
      0.01. CONCLUSION: Using balloon interposition as a protective device has
      advantages over previous saline infusion or CO2 insufflation, providing a safe
      way to expand percutaneous RFA of liver tumors located on the undersurface of the
      diaphragm. In addition, this method may be used in protection of other organs
      adjacent to areas being ablated.

PMID- 24678434
TI  - Non-resolving Findings in a Long-term Radiographic Follow-up of an Infant with
      Acute Paraffin Oil Aspiration.
AB  - Acute lipoid pneumonia (LP) in children is a rare disorder caused by the
      aspiration of oil-based substances and is difficult to diagnose due to non
      specific clinical symptoms and radiological findings. We report the case of a 5
      month-old male infant with acute LP caused by accidental aspiration of a large
      amount of mineral oil. We present the imaging findings in the computed tomography
      scans performed during his hospitalization and focus on the residual
      abnormalities seen on a scan performed 7-years after the incident. This, to the
      best of our knowledge, is the longest follow-up report of an acute exogenous LP
      patient and the only case that demonstrates non-resolving abnormalities in a
      pediatric patient after a single acute episode of mineral oil aspiration. 

PMID- 24678435
TI  - Nonfunctional islet cell tumor of the pancreas in a patient with tuberous
      sclerosis: a case report with literature review.
AB  - Islet cell tumors (ICTs) are rare tumors of the pancreas. Association of this
      type of tumor with tuberous sclerosis is extremely rare. Only 13 cases of
      pancreatic ICT with tuberous sclerosis have so far been documented in the
      literature. However, awareness of the association of tuberous sclerosis and ICT
      is important for early diagnosis and appropriate treatment of this condition.
      This article presents the case of a 63-year-old female with angiomyolipoma (AML)
      of the kidney and liver, calcified subependymal nodules and a large mass in the
      pancreas, which was proven to be an ICT on histopathological examination. 

PMID- 24678436
TI  - Malignant melanoma of the rectum.
AB  - Malignant melanoma of the rectum is an extremely rare disease. It typically
      presents in the fifth or sixth decade of life with nonspecific complaints such as
      rectal bleeding or anal pain. A timely diagnosis of anal melanoma is made even
      more difficult by the fact that most of the lesions lack obvious pigmentation and
      are even histologically amelanotic. Prognosis is very poor. Anorectal malignant
      melanomas spread along submucosal planes and are often beyond complete resection
      at the time of diagnosis. We present the radiological and pathological features
      seen in a 43-year-old woman diagnosed with melanoma of the rectum. 

PMID- 24678437
TI  - Symmetrical Chorioretinal Colobomata with Craniovertebral Junction Anomalies in
      CHARGE Syndrome - A Case Report with Review of Literature.
AB  - CHARGE syndrome is a common cause of congenital anomalies. Its rate of incidence
      is about 1:10,000. It is phenotypically heterogeneous, usually a sporadic or
      autosomal dominant disorder resulting from a mutation in the CHD7 (chromodomain
      helicase DNA-binding protein) gene. Since the time it was first described by
      Hall,[1] the knowledge of the clinical characteristics of CHARGE syndrome has
      increased over the years. Recently, basiocciput hypoplasia and basilar
      invagination in patients with CHARGE syndrome have been reported. We report here
      a case of CHARGE syndrome where there is involvement of symmetrical chorioretinal
      colobomata with craniovertebral junction anomalies. The patient had symmetrical
      chorioretinal colobomata, external and inner ear anomalies, sensorineural
      deafness, characteristic facial appearance, retarded growth and development,
      history of patent ductus arteriosus, and craniovertebral junction anomalies.
      Craniovertebral junction anomalies may be an under-diagnosed phenotypic
      expression of CHARGE syndrome. The diagnostic criteria of CHARGE syndrome may
      require further revision to include the addition of craniovertebral junction
      anomalies. 

PMID- 24678438
TI  - Two Cases of Spinal, Extraosseous, Intradural Ewing's sarcoma/Peripheral
      Neuroectodermal Tumor: Radiologic, Pathologic, and Molecular Analysis.
AB  - Extraosseous Ewing's sarcoma/peripheral neuroectodermal tumors (ES/PNETs) are
      rare neoplasms that account for approximately 10%-15% of soft tissue sarcomas in
      children and 5% of soft tissue sarcomas in adults. Primary spinal, extraosseous,
      intradural ES/PNETs are even less common. The diagnosis of ES/PNET is extremely
      challenging, because the tumor can have a nonspecific radiologic appearance, and
      the histologic features are shared by many other "small round cell tumors." Thus,
      ES/PNET should be included in the radiologic and pathologic differential
      diagnosis, even in older patients and in unusual tumor sites. We report two cases
      of spinal, extraosseous, intradural ES/PNETs in adults who presented with back
      pain. Magnetic resonance imaging revealed contrast enhancing, intradural lesions
      in the area of the conus medullaris. The tumor in Case 1 was partially
      intramedullary, while the tumor in Case 2 was exclusively extramedullary. In both
      cases, the radiologic and intraoperative surgical impression favored ependymoma.
      The diagnosis of ES/PNET was established in both cases by histopathologic,
      immunohistochemical, and molecular analysis. 

PMID- 24678439
TI  - The role of veterans affairs in emergency management: a systematic literature
      review.
AB  - The Department of Veterans Affairs (VA) is a key player in emergency management
      for both veterans and civilians. Unfortunately, limited evidence-based research
      findings exist regarding the role and experience of VA during disasters. The
      present study is a systematic literature review of 41 published, peer-reviewed
      articles regarding VA and emergency management. Trained researchers utilized a
      data abstraction tool and conducted a qualitative content analysis. A description
      of article characteristics include methodology, phase of emergency management
      addressed in the research, and study design. Five topic categories emerged from
      the review including effects of disaster on mental health status and services
      use, effects of disaster on general health services use, patient tracking,
      evacuation, and disaster planning/preparation. Findings were used to generate
      suggestions for future research. KEYWORDS: Veterans Affairs, veterans, disaster,
      emergency.

PMID- 24678440
TI  - Review of the OSHA-NIOSH Response to the Deepwater Horizon Oil Spill: Protecting
      the Health and Safety of Cleanup Workers.
AB  - INTRODUCTION: The fire and explosion of the Deepwater Horizon oil rig resulted in
      an enormous oil spill that threatened large distances of coastline. The overall
      response was led by the United States Coast Guard and involved the oil company
      BP, federal agencies, and state and local governments of five states. METHODS:
      The Occupational Safety and Health Administration and the National Institute for
      Occupational Safety and Health focused extensive resources on ensuring that BP
      and its contractors provided safe working conditions for thousands of workers
      involved in the response. Federal personnel visited worksites daily, identifying
      hazards and means of abatement; assessed training programs to ensure that workers
      were adequately trained in languages they could understand; monitored chemical
      exposures and determined that the proper personal protective equipment was
      deployed; insisted on implementation of a heat mitigation program; rostered
      thousands of workers; and conducted extensive outreach in communities impacted by
      the spill. RESULTS: Advance planning, immediate deployment, and collaboration
      across agencies helped ensure that the response operations resulted in no worker
      fatalities, and relatively few injuries and illnesses. CONCLUSIONS: For future
      responses, improvements should be made in how safety and health information, as
      well as the process behind safety and health decisions, are communicated to the
      public. CITATION: Michaels D, Howard J. Review of the OSHA-NIOSH Response to the
      Deepwater Horizon Oil Spill: Protecting the Health and Safety of Cleanup Workers.
      PLoS Currents Disasters. 2012 Jul 18.

PMID- 24678441
TI  - The gender analysis tools applied in natural disasters management: a systematic
      literature review.
AB  - BACKGROUND: Although natural disasters have caused considerable damages around
      the world, and gender analysis can improve community disaster preparedness or
      mitigation, there is little research about the gendered analytical tools and
      methods in communities exposed to natural disasters and hazards. These tools
      evaluate gender vulnerability and capacity in pre-disaster and post-disaster
      phases of the disaster management cycle. OBJECTIVES: Identifying the analytical
      gender tools and the strengths and limitations of them as well as determining
      gender analysis studies which had emphasized on the importance of using gender
      analysis in disasters. METHODS: The literature search was conducted in June 2013
      using PubMed, Web of Sciences, ProQuest Research Library, World Health
      Organization Library, Gender and Disaster Network (GDN) archive. All articles,
      guidelines, fact sheets and other materials that provided an analytical framework
      for a gender analysis approach in disasters were included and the non-English
      documents as well as gender studies of non-disasters area were excluded. Analysis
      of the included studies was done separately by descriptive and thematic analyses.
      RESULTS: A total of 207 documents were retrieved, of which only nine references
      were included. Of these, 45% were in form of checklist, 33% case study report,
      and the remaining 22% were article. All selected papers were published within the
      period 1994-2012. CONCLUSIONS: A focus on women's vulnerability in the related
      research and the lack of valid and reliable gender analysis tools were
      considerable issues identified by the literature review. Although non-English
      literatures with English abstract were included in the study, the possible
      exclusion of non-English ones was found as the limitation of this study.

PMID- 24678442
TI  - Yoga Improves Upper-Extremity Function and Scapular Posturing in Persons with
      Hyperkyphosis.
AB  - OBJECTIVE: Hyperkyphosis (excess thoracic spine curvature) is associated with
      upper-extremity functional limitations and altered scapular posturing. The
      purpose of this study was to quantify the changes in upper-extremity function and
      scapular posturing following a 6-month yogaintervention in persons with
      hyperkyphosis. METHODS: Twenty-one older adults with hyperkyphosis (75.5+7.4 yrs)
      enrolled in the UCLA Yoga for Kyphosis randomized controlled trial, elected to
      participate in this uncontrolled, prepost substudy of upper-extremity function.
      They were measured at baseline and after a 24-week yoga intervention. Maximum
      vertical reach and timed book tests were used to evaluate upper-extremity
      function. Scapular posturing was quantified using a motion analysis system and
      data was obtained under 4 conditions: 1) quiet-standing, 2) normal walking, 3)
      fast walking, and 4) seated. Paired t-tests were used to test for changes between
      baseline and 6-month follow-up measures and Cohen's d was calculated to examine
      effect sizes. RESULTS: Following the 6-month yoga intervention, participants
      improved their book test performance by 26.4% (p < 0.001; d = 1.5). Scapular
      protraction decreased by 2.9% during the static-sitting condition (p < 0.001; d =
      0.5) and the overall excursion of the scapulae decreased for both fast (25.0%, p
      < 0.05; d = 0.6) and self-selected walking (29.4%, p < 0.01; d = 0.9). There were
      no changes in maximum vertical reach. CONCLUSION: Subjects demonstrated
      significant improvements with small to large effect sizes in the timed book test
      and scapular posturing to a less protracted position during both static and
      dynamic conditions after the intervention. These adaptations are likely to reduce
      the risk of scapular impingement and help preserve functional independence in
      older adults.

PMID- 24678443
TI  - Extrinsic Regulation of Satellite Cell Function and Muscle Regeneration Capacity
      during Aging.
AB  - Optimal regeneration of skeletal muscle in response to injury requires the
      contribution of tissue resident stem cells termed satellite cells. Normally
      residing at the interface between the muscle fiber and overlying basal lamina it
      is generally understood with age the satellite cell pool exhibits decline both in
      number and function. Over the past decade mechanisms that contribute to these
      declines have begun to emerge. Implicit in aged-related satellite cell
      dysfunction and decline is the involvement of signals from the environment. Many
      of the signals that become deregulated with age have conserved functions during
      distinct stages of muscle fiber formation both in early development and
      regeneration. In particular, modulations in Wnt, TGFbeta, Notch and FGF emanating
      from aged skeletal muscle fibers or the systemic milieu have emerged as age
      related alterations that significantly impact both the maintenance of the
      satellite cell pool and skeletal muscle regenerative efficacy. In this review we
      will summarize how the aforementioned pathways contribute to skeletal muscle
      development and regeneration. We will then discuss deregulation of these cascades
      with age and how they contribute to satellite cell depletion and dysfunction. The
      review will also summarize some of the challenges we face in trying to draw
      parallels between murine and human satellite cell aging. Finally, we will
      highlight the few examples whereby FDA approved drugs may be exploited to
      modulate specific signaling cascades in effort to preserve skeletal muscle
      regenerative function with age.

PMID- 24678444
TI  - Bilateral gluteal dyskinesia: discussion of a rare movement disorder.
AB  - BACKGROUND: Involuntary movements of gluteal muscles have rarely been reported.
      CASE REPORT: This 46-year-old female with pelvic endometriosis developed
      involuntary rhythmic movements in the left gluteus maximus, which within a year
      became bilateral. The movements gradually increased in intensity and interfered
      with ambulation. Electromyography, at rest, demonstrated almost continuous
      periodic gluteal discharges, with left-sided discharges seeming to lead to those
      on the right. OnabotulinumtoxinA injections into the gluteal muscles improved the
      movements. DISCUSSION: A rare and previously unreported form of gluteal
      involuntary movements with periodic electromyographic discharges is described.
      The cause is uncertain. The differential diagnosis of this unusual movement
      disorder is discussed, with the most likely diagnosis being myoclonus.

PMID- 24678445
TI  - Depression and Disordered Eating in the Obese Person.
AB  - Three mental health problems commonly associated with obesity are major
      depression, binge eating disorder (BED), and Night Eating Syndrome (NES).
      Evidence from both cross-sectional and longitudinal studies support independent
      relationships between obesity and depression, and between obesity and binge
      eating. These problems are most prevalent in severely obese individuals (Class
      III obesity; a body mass index (BMI) of >40kgm(2)), many of whom seek bariatric
      surgery, and we briefly review whether the presence of pre-operative depression,
      BED or NES affects post-operative outcomes. Historically depressed individuals
      have been screened out of weight loss trials due to concerns of worsening mood
      with weight loss. Such practices have precluded the development of effective
      treatments for depressed, obese individuals, leaving large numbers of people
      without appropriate care. We present recent advances in this area, and attempt to
      answer whether depressed individuals can lose clinically significant amounts of
      weight, show improvements in mood, and adhere to the demands of a weight loss
      intervention. 

PMID- 24678446
TI  - Cardiovascular Admissions, Readmissions, and Transitions of Care.
AB  - Hospital 30-day readmissions have become a major priority for hospitals.
      Hospitals face penalties for excessive readmissions for acute myocardial
      infarction (AMI) and heart failure (HF). Thus, it is important for hospitals to
      understand the transitions of care that occur for both of these conditions, and
      what tools are available to guide the processes involved. A multi-disciplinary
      team including Emergency Medical Service providers, Emergency Medicine providers,
      cardiologists, hospitalists, pharmacists, nurses, case managers, and outpatient
      physicians can all be involved in the process of safely transitioning a patient
      between care settings. Small-scale studies in the geriatric population have shown
      improved transitions of care and decreased readmissions with these care teams.
      The emergency department is a key transition point for patients with AMI and HF,
      yet it is rarely identified and utilized as such in transitions of care
      interventions. Future research and implementation projects will need to refine
      and expand the role of the emergency department in the process.

PMID- 24678447
TI  - Hepatic RNA Interference: Delivery by Synthetic Vectors.
AB  - Though the pharmaceutical industry's infatuation with the therapeutic potential
      of RNA interference (RNAi) technology has finally come down from its initial
      lofty levels,[1] hope is by no means lost for the once-burgeoning enterprise, as
      recent clinical trials are beginning to show efficacy in areas ranging from
      amyloidosis to hypercholesterolemia to muscular dystrophy. With such resurgence
      comes a more informed perspective on the needs of such therapeutics: a renewed
      focus on true RNA drug development, and a desire for enhanced site-specific
      delivery.[2] In this review, we will discuss the latter with regard to hepatic
      targeting by synthetic vectors, covering the implications of organ and cellular
      physiology on conjugate structure, particle morphology, and active targeting. In
      presenting efficacy in a variety of disease models, we emphasize as well the
      extraordinary degree to which synthetic formulation improves upon and coordinates
      efforts with oligonucleotide development. Such advances in the understanding of
      and the technology behind RNAi have the potential to finally stabilize the long
      term prospects RNA therapeutic development.

PMID- 24678449
TI  - Creating a Single Sensing Zone within an Alpha-Hemolysin Pore Via Site Directed
      Mutagenesis.
AB  - Although significant progress has recently been made towards realizing the goal
      of direct nanopore based DNA sequencing [1], there are still numerous hurdles
      that need to be overcome. One such hurdle associated with the use of the
      biological nanopore alpha-hemolysin (alphaHL) is the fact that the wild type
      channel contains three very distinct recognition or sensing regions within the
      beta-barrel [2, 3], making identification of the bases residing within or moving
      through the pore very difficult. Through site directed mutagenesis, we have been
      able to selectively remove one of two sensing regions while simultaneously
      enhancing the third. Our approach has led to the creation of alphaHL pores
      containing single sensing zones and provides the basis for engineering alphaHL
      pores suitable for direct DNA sequencing.

PMID- 24678448
TI  - Of plasticity and specificity: dialectics of the micro- and macro-environment and
      the organ phenotype.
AB  - The study of biological form and how it arises is the domain of the developmental
      biologists; but once the form is achieved, the organ poses a fascinating
      conundrum for all the life scientists: how are form and function maintained in
      adult organs throughout most of the life of the organism? That they do appears to
      contradict the inherently plastic nature of organogenesis during development. How
      do cells with the same genetic information arrive at, and maintain such different
      architectures and functions, and how do they keep remembering that they are
      different from each other? It is now clear that narratives based solely on genes
      and an irreversible regulatory dynamics cannot answer these questions
      satisfactorily, and the concept of microenvironmental signaling needs to be added
      to the equation. During development, cells rearrange and differentiate in
      response to diffusive morphogens, juxtacrine signals and the extracellular matrix
      (ECM). These components, which constitute the modular microenvironment, are
      sensitive to cues from other tissues and organs of the developing embryo as well
      as from the external macroenvironment. On the other hand, once the organ is
      formed, these modular constituents integrate and constrain the organ
      architecture, which ensures structural and functional homeostasis and therefore,
      organ specificity. We argue here that a corollary of the above is that once the
      organ architecture is compromised in adults by mutations or by changes in the
      microenvironment such as aging or inflammation, that organ becomes subjected to
      the developmental and embryonic circuits in search of a new identity. But since
      the microenvironment is no longer embryonic, the confusion leads to cancer: hence
      as we have argued, tumors become new evolutionary organs perhaps in search of an
      elusive homeostasis.

PMID- 24678450
TI  - Neuroimaging in Alcohol and Drug Dependence.
AB  - Neuroimaging, including PET, MRI, and MRS, is a powerful approach to the study of
      brain function. This article reviews neuroimaging findings related to alcohol and
      other drugs of abuse that have been published since 2011. Uses of neuroimaging
      are to characterize patients to determine who will fare better in treatment and
      to investigate the reasons underlying the effect on outcomes. Neuroimaging is
      also used to characterize the acute and chronic effects of substances on the
      brain and how those effects are related to dependence, relapse, and other drug
      effects. The data can be used to provide encouraging information for patients, as
      several studies have shown that long-term abstinence is associated with at least
      partial normalization of neurological abnormalities.

PMID- 24678451
TI  - NANOG is multiply phosphorylated and directly modified by ERK2 and CDK1 in vitro.
AB  - NANOG is a divergent homeobox protein and a core component of the transcriptional
      circuitry that sustains pluripotency and self-renewal. Although NANOG has been
      extensively studied on the transcriptional level, little is known regarding its
      posttranslational regulation, likely due to its low abundance and challenging
      physical properties. Here, we identify eleven phosphorylation sites on endogenous
      human NANOG, nine of which mapped to single amino acids. To screen for the
      signaling molecules that impart these modifications, we developed the multiplexed
      assay for kinase specificity (MAKS). MAKS simultaneously tests activity for up to
      ten kinases while directly identifying the substrate and exact site of
      phosphorylation. Using MAKS, we discovered site-specific phosphorylation by ERK2
      and CDK1/CyclinA2, providing a putative link between key signaling pathways and
      NANOG. 

PMID- 24678454
TI  - A Case Study of Hispanics and Hospice Care.
AB  - The issues of death and dying that have given impetus to the hospice movement
      include the effect on people with terminal illnesses and their families,
      impending death, renewed attention to long-term care centers and other
      alternatives to hospitalization, the scarcity of resources, the emphasis on
      holistic health, and recognition of the rights of people who are dying to die
      with dignity. Hospice offers patients compassionate care that is focused the pain
      relief and symptom management so that they can die a good death. In the US,
      hospice is considered the gold standard of care for terminally ill patients. Yet,
      racial and ethnic minorities are under-represented among those who receive this
      type of care. The present research takes a qualitative approach to exploring
      factors that influence hospice care among Hispanics in a hospice care setting. It
      discusses structural and cultural factors that influence the care among older
      adults. The research reveals organizational and professional that exist.

PMID- 24678452
TI  - Isolation of progenitors that exhibit myogenic/osteogenic bipotency in vitro by
      fluorescence-activated cell sorting from human fetal muscle.
AB  - Fluorescence-activated cell sorting (FACS) strategies to purify distinct cell
      types from the pool of fetal human myofiber-associated (hMFA) cells were
      developed. We demonstrate that cells expressing the satellite cell marker PAX7
      are highly enriched within the subset of CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(
      )CD56(int)ITGA7(hi) hMFA cells. These CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(
      )CD56(int)ITGA7(hi) cells lack adipogenic capacity but exhibit robust, bipotent
      myogenic and osteogenic activity in vitro and engraft myofibers when transplanted
      into mouse muscle. In contrast, CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(+) fetal hMFA
      cells represent stromal constituents of muscle that do not express PAX7, lack
      myogenic function, and exhibit adipogenic and osteogenic capacity in vitro. Adult
      muscle likewise contains PAX7(+) CD45(-)CD11b(-)GlyA(-)CD31(-)CD34(
      )CD56(int)ITGA7(hi) hMFA cells with in vitro myogenic and osteogenic activity,
      although these cells are present at lower frequency in comparison to their fetal
      counterparts. The ability to directly isolate functionally distinct progenitor
      cells from human muscle will enable novel insights into muscle lineage
      specification and homeostasis. 

PMID- 24678455
TI  - Harnessing the potential of bacterial ghost for the effective delivery of drugs
      and biotherapeutics.
AB  - It seems to be a necessary need to develop an effective drug carrier system for
      targeted delivery of pharmaceuticals. Bacterial ghosts are emerging drug delivery
      platform that are capable of delivery of proteins, antigens, nucleic acids, and
      pharmaceuticals. Bacterial ghosts are generally produced by lysis of gram
      negative bacteria. Pharmaceutically, these ghosts could be utilized to deliver
      proteins peptides, vaccines, drugs effectively. However, this technology is at
      initial stage and systematic studies are required to implement such system over
      humans. 

PMID- 24678453
TI  - Efficient designer nuclease-based homologous recombination enables direct PCR
      screening for footprintless targeted human pluripotent stem cells.
AB  - Genetic engineering of human induced pluripotent stem cells (hiPSCs) via
      customized designer nucleases has been shown to be significantly more efficient
      than conventional gene targeting, but still typically depends on the introduction
      of additional genetic selection elements. In our study, we demonstrate the
      efficient nonviral and selection-independent gene targeting in human pluripotent
      stem cells (hPSCs). Our high efficiencies of up to 1.6% of gene-targeted hiPSCs,
      accompanied by a low background of randomly inserted transgenes, eliminated the
      need for antibiotic or fluorescence-activated cell sorting selection, and allowed
      the use of short donor oligonucleotides for footprintless gene editing. Gene
      targeted hiPSC clones were established simply by direct PCR screening. This
      optimized approach allows targeted transgene integration into safe harbor sites
      for more predictable and robust expression and enables the straightforward
      generation of disease-corrected, patient-derived iPSC lines for research purposes
      and, ultimately, for future clinical applications. 

PMID- 24678456
TI  - Thermosensitive periodontal sol of ciprofloxacin hydrochloride and
      serratiopeptidase: Pharmaceutical and mechanical analysis.
AB  - AIM: The aim of the present work was to explore the development of a dual
      controlled release periodontal system of a potent broad spectrum first-generation
      fluoroquinolone, ciprofloxacin, and the anti-inflammatory enzyme
      serratiopeptidase (STP). MATERIALS AND METHODS: Based on 3(2) full factorial
      design, thermoreversible periodontal sols capable of controlled dual delivery of
      ciprofloxacin hydrochloride and STP were designed using pluronic F127 and
      carbopol 934P as thermosensitive gelling polymers. Sol gel transition
      characteristics, %cumulative drug release at 48(th) h and exvivo mucoadhesive
      strength were designated as dependent responses. The sols were mucoadhesive,
      syringeable, and inverted into gels at simulated periodontal cavity temperature.
      RESULTS: F9 with optimal drug release was identified as the best formulation.
      Extra design check point generated using Design Expert software 8.02 (Stat-Ease,
      USA) validated the experimental design. Textural analysis revealed that the
      developed sols were syringeable and spreadable enough for periodontal treatment
      so it can be expected that hardness and compressibility of sols would pose no
      problem during clinical application. The in vitro release behavior exhibited
      controlled release of both cipro HCl and STP (>90% release). CONCLUSION: A dual
      controlled release thermoreversible periodontal sol of ciproflaxin and STP was
      successfully developed. Incorporation of STP as anti-inflammatory agent has the
      potential of developing a therapeutically efficacious system of cipro HCl for
      treatment of periodontal inflammatory anaerobic infections.

PMID- 24678457
TI  - Polyethylene glycolated PAMAM dendrimers-Efavirenz conjugates.
AB  - AIM: The preparation of novel PEGylated PAMAM (poly-amidoamine) dendrimers for
      delivery of anti-HIV drug Efavirenz is reported. METHOD AND MATERIALS: About 5.0
      G PAMAM dendrimers are prepared by ethylene diamine core via Michael addition by
      divergent method. PEGylation is done by polyethylene glycol 600 using
      epichlorhydrin as linker. PEGylated 5.0 G PAMAM dendrimers loaded with Efavirenz
      (EFV) are evaluated for FTIR, DSC, SEM, drug release, and stability studies.
      RESULTS AND CONCLUSION: From the results it is proved that this method is less
      time consuming, inexpensive, and reproducible. Drug-release studies indicate,
      PEGylated 5.0 G PAMAM-EFV dendrimers have shown prolonged drug-release property.

PMID- 24678458
TI  - Design, development and evaluation of clopidogrel bisulfate floating tablets.
AB  - OBJECTIVE: The objective of the present work was to formulate and to characterize
      a floating drug delivery system for clopidogrel bisulphate to improve
      bioavailability and to minimize the side effects of the drug such as gastric
      bleeding and drug resistance development. MATERIALS AND METHODS: Clopidogrel
      floating tablets were prepared by direct compression technique by the use of
      three polymers xanthan gum, hydroxypropyl methylcellulose (HPMC) K15M and HPMC
      K4M in different concentrations (20%, 25% and 30% w/w). Sodium bicarbonate (15%
      w/w) and microcrystalline cellulose (30% w/w) were used as gas generating agent
      and diluent respectively. Studies were carried out on floating behavior and
      influence of type of polymer on drug release rate. All the formulations were
      subjected to various quality control and in-vitro dissolution studies in 0.1 N
      hydrochloric acid (1.2 pH) and corresponding dissolution data were fitted to
      popular release kinetic equations in order to evaluate release mechanisms and
      kinetics. RESULTS AND DISCUSSION: All the clopidogrel floating formulations
      followed first order kinetics, Higuchi drug release kinetics with diffusion as
      the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the
      release exponent "n" ranged 0.452-0.654 indicating that drug release from all the
      formulations was by non-Fickian diffusion mechanism. The drug release rate of
      clopidogrel was found to be affected by the type and concentration of the polymer
      used in the formulation (P < 0.05). As the concentration of the polymer was
      increased, the drug release was found to be retarded. CONCLUSION: Based on the
      results, clopidogrel floating tablets prepared by employing xanthan gum at
      concentration 25% w/w (formulation F2) was the best formulation with desired in
      vitro floating time and drug dissolution.

PMID- 24678459
TI  - Preparation and evaluation of sublingual tablets of zolmitriptan.
AB  - AIM: Zolmitriptan is a 5-HT receptor agonist (1B/1D). It is used in the acute
      treatment of migraine having low bioavailability about 40% orally due to hepatic
      first pass metabolism. The purpose of the present research was to formulate fast
      acting sublingual tablets of zolmitriptan. MATERIALS AND METHODS: Sublingual
      tablets were prepared using ispaghula husk powder, gellan gum, sodium alginate as
      super disintegrating polymers and citric acid, tartaric acid and camphor as
      permeation enhancers by direct compressible technique and evaluated for weight
      variation, thickness, friability, content uniformity, hardness, disintegration
      time, wetting time, in-vitro drug release, in-vitro and ex-vivo permeation study.
      Stability study of optimized formulation was performed as per ICH (International
      Conference on Harmonisation) guideline. RESULTS: The in-vitro disintegration time
      of the optimized formulation (D5) was 9 +/- 2 s and all formulations showed 100%
      of dissolution within 6 +/- 2 min. Formulation containing 4% of gellan gum (D5)
      showed highest disintegration and 2% of citric acid formulation (P3) showed
      highest permeation 88% within 30 min and ex-vivo permeation was 52% within 30
      min. Optimized formulation was stable for 1 month during stability study as per
      ICH guideline. CONCLUSION: The sublingual tablet formulation gives better results
      using natural super disintegrant for fast onset of action.

PMID- 24678460
TI  - Preparation and evaluation of chitosan microspheres containing nicorandil.
AB  - OBJECTIVES: The objective of present study was to develop chitosan-based
      sustained release nicorandil microspheres to reduce the dosing frequency.
      MATERIALS AND METHODS: The nicorandil-loaded chitosan microspheres were
      formulated by emulsion crosslinking method. A 3(2) factorial design was employed
      to study the influence of drug: Polymer ratio and volume of glutaraldehyde (GA)
      on percentage entrapment efficiency, particle size, and % drug release at 8 h.
      RESULTS: The entrapment efficiency was found to be 41.67 +/- 1.43-77.33 +/- 1.97%
      and particle size range 65.67 +/- 2.08-146.67 +/- 2.18 MUm. The batch CH5 showed
      79.11 +/- 2.23 and 96.21 +/- 2.41% drug release at 8 and 12 h, respectively.
      CONCLUSIONS: DRUG: Polymer ratio and volume of GA had significant effect on %
      entrapment efficiency, particle size, and % drug release. From the scanning
      electron microscopy (SEM) study observed that microspheres were spherical and
      fairly smooth surface. Fickian diffusion was the mode of drug release from
      nicorandil-loaded chitosan microspheres formulations.

PMID- 24678461
TI  - Formulation and evaluation of polyelectrolyte complex-based matrix tablet of
      Isosorbide Mononitrate.
AB  - INTRODUCTION: The polyelectrolyte Complexes (PECs) are based on ionic cross
      linking. They have been employed to prepare a sustained release matrix tablets.
      These systems are based upon the fact that their structure can entrap the drug
      within them. Isosorbide Mononitrate (ISMN) is an anti-anginal organic nitrate
      vasodilator used in the treatment of various cardiovascular disorders and
      prophylaxis of angina Pectoris, which is poorly absorbed from the upper GIT,
      hence CR formulation is desirable. MATERIALS AND METHODS: Chitosan (CH)/Sodium
      alginate (SA), Guar gum (GG), and Xanthan gum (XG) were used as PECs, and were
      prepared using different proportions i.e., in 1:1 and 1:2 ratio. The optimum
      ratio of CH: SA, CH: GG and CH: XG was in the ratio was 1:2; these are formed due
      to electrostatic interaction between oppositely charged poly ions. These normally
      employ a hydrophilic matrix system. Matrix tablet of ISMN was formulated by using
      PECs as matrix forming agent by wet granulation technique. RESULTS: The tablets
      were evaluated for hardness, wt variation, drug content, and in-vitro dissolution
      studies and found to be within limits. Release kinetics data indicated that ISMN
      released from the PECs-based matrix tablets of CH-SA, CH-GG and CH-XG CP in 1:1
      and 1:2 ratio, followed Fickian and non-Fickian diffusion mechanism respectively.
      Thus, the drug release rate was extended for over a period of more than 12 h
      stability studies. There is no significant difference in the mean % drug released
      from formulation CH-X2 after storing for 3 months at 40 degrees C/75% RH. The FT
      IR spectra revealed that there was no interaction between polymers and drug,
      Statistical analysis showed a significant differences (P < 0.05) for the amount
      of ISMN released from the formulations (MXG) and formulations (CH-X2).
      CONCLUSION: Formulation CH-XG2 (1:2) showed better sustained release of highly
      water-soluble ISMN with the desired release rate. Thus, the formulated PECs-based
      matrix tablets seems to be a potential candidate for sustained drug delivery of
      highly soluble drug ISMN in the symptomatic therapy of angina pectoris.

PMID- 24678462
TI  - Starting the Conversation - A Childhood Obesity Knowledge Project Using an App.
AB  - PURPOSE: Starting the Conversation was a pilot project to test an intervention
      for childhood obesity, a major public health epidemic, using a free smartphone
      application (app). The primary aim was to assess students' knowledge of
      nutritional indicators, physical exercise and use of screen time before and after
      the intervention. METHODS: The study was conducted in 2011-2012. The sample,
      recruited from seven high schools in Snohomish County, Washington, was 65.3%
      minority participants. Of the 118 participants in the sample (n=118), 79
      handwrote their responses (n=78) and 36 responded via the app (n=39). We compared
      the frequency and types of physical exercise, frequency of screen time, and
      nutritional variables of high school students. Participants used the cell phone
      app or a handwritten log to record their daily entries for 20 days. RESULTS: Both
      males (n=43) and females (n=75) grades 9-12 used the app or handwritten entries.
      Participants who used the app ate less fast food and exercised more, as compared
      with those who recorded their entries by hand. Screen time usage decreased over
      the course of the study, based on a comparison of the post-survey level and the
      pre-survey level. Knowledge of recommended daily consumption of vegetables
      increased post-test in the app group and knowledge of water consumption increased
      significantly in both groups. There was no significant difference in BMI pre and
      post-test. CONCLUSIONS: Patterns of nutritional intake, physical exercise and
      knowledge of these issues varied pre and post-test. It is critical to further
      examine factors associated with lack of physical activity and food intake
      patterns of youth using social media to further address the childhood obesity
      epidemic. Future research should focus on specific ethnic subgroups and an
      intervention at the school level aimed at the students with BMI >= 95th
      percentile.

PMID- 24678463
TI  - Utility of total lymphocyte count as a surrogate for absolute CD4 count in the
      adult Indian HIV population: A prospective study.
AB  - BACKGROUND: Standard methods of CD4 counts and plasma viral load estimation
      require specialized equipment, highly trained personnel and are extremely
      expensive. This remains a major challenge for the initiation of anti-retroviral
      therapy for patients in resource-limited settings. OBJECTIVE: To assess the
      clinical utility of the total lymphocyte count (TLC) to serve as a surrogate
      marker for predicting a CD4 counts <350 cell/mm(3) in patients with HIV.
      MATERIALS AND METHODS: A prospective study of 200 consecutive newly detected
      highly active anti-retroviral therapy (HAART) naive HIV patients admitted over a
      one year period was conducted. Linear regression, Pearson correlation and
      receiver operating characteristic (ROC) curves were used to calculate the
      relationship between TLC and CD4 counts. RESULTS: A significant correlation
      between TLC and CD4 count was observed (r = 0.682, P < 0.001). TLC cut off of
      1200 cell/mm(3) as a predictor of CD4 count <350 cell/mm(3) had 73.1%
      sensitivity, 100% specificity, 100% positive predictive value (PPV) and 51.4%
      negative predictive value (NPV). Raising the cutoff to 1500 cells/mm(3) improved
      the sensitivity to 82.1% with 88.2% specificity, 96.5% PPV, 44.4% NPV. The ROC
      curve demonstrated highest area under curve (AUC = 0.8) for TLC of 1500
      cell/mm(3). CONCLUSION: The study showed that TLC cutoff value of 1500
      cells/mm(3) was a cost effective surrogate marker for CD4 counts <350 cells/mm(3)
      in resource-limited settings.

PMID- 24678464
TI  - Risk factors associated with deciduous tooth decay in Iraqi preschool children.
AB  - INTRODUCTION: Tooth decay (TD) is common in children with significant
      consequences on systemic well-being, growth and quality of life, as well as
      increasing the risk of decay in the permanent teeth. AIM: The aim of the present
      study is to define risk factors associated with deciduous TD (DTD) in Iraqi
      preschool children. MATERIALS AND METHODS: From the 1(st) June to 31(st) December
      2012, a case-control study was carried out on 684 children under the age of 6
      years who attended Al-Aulwyiah pediatric teaching hospital in Baghdad. Clinical
      examination and World Health Organization caries diagnostic criteria for decayed,
      missing and filled teeth (DMFT) were applied. Data including gender, residence,
      socio-economic status (SES), parental education level, parental smoking, tooth
      brushing frequency, type of feeding during infancy and the presence of any
      systemic disease in the child were sought. RESULTS: The mean DMFT score in the
      case group was 2.03 +/- 1.39, of which decayed teeth formed 1.93. Males had a
      higher mean DMFT (2.10 +/- 1.08) than females (1.96 +/- 1.70) but with no
      statistically significant difference. The study revealed that residence, SES,
      parental education level and tooth brushing frequency were dependent risk factors
      significantly associated with DTD. However, gender, parental smoking and pattern
      of feeding during infancy were not significantly associated with DTD. Only four
      children with systemic disorders (1.2%), namely asthma and congenital heart
      diseases, were noticed to have DTD. CONCLUSION: Pediatricians and dentists could
      provide dental preventive and screening measures. Confronting relevant risk
      factors associated with DTD and improving access to oral care services are
      suggested. In addition, promotion of oral health programs through school
      curricula is needed.

PMID- 24678465
TI  - Avicenna's contribution to cardiology.
AB  - Ibn Sina, known in the West as Avicenna, was the most famous and influential of
      all the Islamic philosopher-scientists. His most important medical works are the
      Canon of Medicine medical encyclopedia and a treatise on cardiac drugs. His Canon
      of Medicine remained the standard text in both the East and West until the 16(th)
      century. Avicenna's description of cardiac diseases was logically presented
      perhaps for the first time in the history of medicine. Avicenna was the first to
      describe carotid sinus hypersensitivity, which presents with vasovagal syncope.
      He was a pioneer in pulsology and the first correct explanation of pulsation was
      given by Avicenna, after he refined Galen's theory of the pulse. Besides, he
      discussed the action of available drugs on the heart in details and mentioned
      their indications and contraindications. In conclusion, Avicenna made important
      contributions to cardiology. This article describes some of his contributions in
      this field. 

PMID- 24678466
TI  - The first linezolid-resistant Enterococcus faecium in India: High level
      resistance in a patient with no previous antibiotic exposure.
AB  - Linezolid provides high rates of the clinical cure and microbiological success in
      complicated infections due to Enterococcus spp., including vancomycin-resistant
      Enterococcus faecium. However, the emergence of resistance during linezolid
      treatment has been reported for clinical strains of Enterococcus, which is
      alarming given the fact that, this leaves the clinician with very few treatment
      options. We report the first case of linezolid resistant Enterococcus faecium
      from India, which was isolated from the blood culture of a hypoglycemic
      encephalopathy patient. There have been previous reports of linezolid resistant
      enterococci from different parts of the world, with minimum inhibitory
      concentration (MIC) ranging from 16 to 64 MUg/mL and most of them were associated
      with vancomycin resistance but the isolate reported over here had an MIC of 1024
      MUg/mL and interestingly was sensitive to vancomycin. 

PMID- 24678467
TI  - Isolation of Mycobacterium branderi, an unusual species from an acute myelogenous
      leukemia patient.
AB  - We report a case of pulmonary infection caused by Mycobacterium branderi, a slow
      growing non-tuberculosis mycobacteria, in a patient with acute myelogenous
      leukemia. The pulmonary disease was treated successfully with the combination of
      Ciprofloxacin, Doxycycline and Clarithromycin. M. branderi may be considered as
      an opportunistic pathogen, especially among immunologically compromised patients.

PMID- 24678468
TI  - Reactivation of latent melioidosis presenting with acute pyelonephritis and
      bacteremia.
AB  - We report an interesting case involving an 81-year-old male patient who presented
      to our hospital with sepsis secondary to pyelonephritis and bacteremia. Blood
      cultures were positive for a Gram-negative bacillus, Burkholderia pseudomallei.
      His risk factors were diabetes, chronic obstructive pulmonary disease including
      travel to an endemic area. The patient received antibiotic therapy in accordance
      with the national guidelines. This is the first report of reactivation of latent
      melioidosis in the literature manifesting as pyelonephritis and bacteremia. 

PMID- 24678469
TI  - Color-Doppler ultrasound in the diagnosis of oral vascular anomalies.
AB  - In last few years, thanks to laser technology with minimally invasive approach,
      there was a growing need for treatment of oral vascular malformations inside the
      dental offices. Generally, the diagnosis of oral vascular malformations is based
      on clinical history, clinical examination and imaging exams. In the present
      paper, we review, researching by PubMed, the technical aspects, clinical
      indications, potentialities and limitations of color-Doppler ultrasound in the
      work-up of oral vascular malformations. Different imaging modalities are
      encountered for the diagnosis and follow-up of these lesions such as computed
      tomography, magnetic resonance imaging, color-Doppler ultrasound and angiography.
      To date, color-Doppler ultrasound is considered the first-line imaging approach
      since it provides a non-invasive, cost effective, real time evaluation of oral
      vascular anomalies. It provides both morphological and vascular information,
      which are useful to determine the best therapeutic options. Ultrasonography, for
      these reasons, could be considered as a valuable diagnostic tool in the
      preliminary assessment of oral vascular anomalies. 

PMID- 24678470
TI  - Knowledge and attitude of dental professionals of north India toward plagiarism.
AB  - BACKGROUND: Plagiarism is stealing of some others work or idea without proper
      citation. It is one of the biggest challenges faced by the scholarly world and by
      far a grim form of delinquency in academics. AIM: The study was designed to
      explore the knowledge and attitudes of dental professionals toward plagiarism.
      MATERIALS AND METHODS: A questionnaire having 14 questions was sent either via e
      mails or by sending printed copies to 5000 dental professionals, while
      maintaining anonymity of all the participants. RESULT: Most of the dental
      professionals know about plagiarism, and they believe that plagiarism cannot be
      avoided successfully. Pressure to publish was a major reason along with several
      others, which accounts for more and more indulgence in plagiarism. At the same
      time lack of facilities in private institutions and lack of funding for research
      work were the major factors as well, which hinder in creating research
      environment and hence promotes plagiarism and false studies to publish it.
      CONCLUSION: Plagiarism is present in dental professionals and that significant
      reduction can only be brought by awareness, objective check methods and stringent
      punishment. Plagiarism and other forms of academic misconduct must be recognized
      and must not be tolerated.

PMID- 24678471
TI  - Prehospital versus Emergency Room Intubation of Trauma Patients in Qatar: A-2
      year Observational Study.
AB  - BACKGROUND: The impact of prehospital intubation (PHI) in improving outcome of
      trauma patients has not been adequately evaluated in the developing countries.
      AIMS: The present study analyzed the outcome of PHI versus emergency room
      intubation (ERI) among trauma patients in Qatar. MATERIALS AND METHODS: Data were
      retrospectively reviewed for all intubated trauma patients between 2010 and 2011.
      Patients were classified according to location of intubation (PHI: Group-1 versus
      ERI: Group-2). Data were analyzed and compared. RESULTS: Out of 570 intubated
      patients; 482 patients (239 in group-1 and 243 in group-2) met the inclusion
      criteria with a mean age of 32 ? 14.6 years Head injury (P = 0.003) and multiple
      trauma (P = 0.004) were more prevalent in group-1, whereas solid organ injury
      predominated in group-2 (P = 0.02). Group-1 had significantly higher mean injury
      severity scoring (ISS), lower Glasgow coma scale (GCS), greater head abbreviated
      injury score and longer activation, response, scene and total emergency medical
      services times. The mortality was higher in group-1 (53% vs. 18.5%; P = 0.001).
      Multivariate analysis showed that GCS [odds ratio (OR) 0.78, P = 0.005) and ISS
      (OR 1.12, P = 0.001) were independent predictors of mortality. CONCLUSIONS: PHI
      is associated with high mortality when compared with ERI. However, selection bias
      cannot be ruled out and therefore, PHI needs further critical assessment in
      Qatar.

PMID- 24678472
TI  - Comparison of Ice Packs Application and Relaxation Therapy in Pain Reduction
      during Chest Tube Removal Following Cardiac Surgery.
AB  - BACKGROUND: Usually the chest tube removal (CTR) has been described as one of the
      worst experiences by patients in the intensive care unit. AIM: This study aimed
      to compare the effects of cold therapy and relaxation on pain of CTR among the
      patients undergoes coronary artery bypass graft surgery. MATERIALS AND METHODS:
      This single-blinded clinical trial was done on 80 post-cardiac surgery patients
      in the heart hospital of Sari-Iran. The patients were assigned to three
      randomized groups that included cold therapy, relaxation, and control groups.
      Data analysis was done by T-test, Chi-square, generalized estimating equations
      and repeated measures analysis variance tests. RESULTS: The groups had no
      significant differences in pain intensity before CTR (P = 0.84), but immediately
      after CTR there was a significant difference between the treatment (cold
      application and relaxation groups) and control groups (P = 0.001). There was no
      significant difference between relaxation and cold therapy groups. CONCLUSION:
      Regarding the relaxation and cold application methods showed relatively equal
      effects on reducing the pain owing to CTR. Thus, the use of relaxation because of
      economics, without side effects, easy to use and effective is recommended by the
      authors to the practitioners.

PMID- 24678473
TI  - Trichomonas, Candida, and gardnerella in cervical smears of Iranian women for
      cancer screening.
AB  - BACKGROUND: Trichomonas vaginalis, Gardrenella vaginalis, and Candida sp are
      responsible for 90% of vaginitis which has been reported as important risk
      factors for cervical cancer. AIM: This study aimed to find the prevalence of T.
      vaginalis, Candida sp, and G. vaginalis in women attended the cancer clinic
      charity, Babol, Iran and to identify the associated risk factors. MATERIALS AND
      METHODS: This retrospective study carried out from 1996 to July 2012 on women who
      attended to a cancer screening program at the cancer clinics charity, Babol,
      Iran. Papanicolaou test and clinical examinations were performed for each woman.
      In addition to Papanicolaou test results, demographic data were collected. The
      data were analyzed with X(2) test using SPSS software, version 18. RESULTS: In
      total, 2511 out of 33600 (7.5%) cases had vaginal infections. A total of 71
      (0.2%), 2248 (6.7%), and 192 (0.6%) of subjects were infected by T. vaginalis,
      Candida sp, and Gardnerella, respectively. The highest rate of infection was seen
      in 20-30 and 30-40 years age group. The frequency of vaginal ulcers was higher in
      trichomoniasis (14.1%). CONCLUSION: This study demonstrated that the prevalence
      of T. vaginalis, Candida sp, and Gardnerella was low among the studied
      population. Moreover, malignant cytological alternations were not seen in any
      infected women.

PMID- 24678474
TI  - Prevalence of Diabetes Mellitus among Tuberculosis Patients in Urban Puducherry.
AB  - BACKGROUND: Diabetes and Tuberculosis often present together and complicate each
      other at many levels. A collaborative framework for care and control of diabetes
      and tuberculosis developed by World Health Organisation and International Union
      against Tuberculosis and Lung Diseases emphasizes routine bi-directional
      screening for the two diseases. AIMS: The study was to assess the prevalence of
      diabetes in tuberculosis patients currently on treatment. MATERIALS AND METHODS:
      This facility-based cross-sectional study was undertaken in four randomly
      selected peripheral health institutions providing directly observed treatment
      short-course, treatment for tuberculosis patients. All cases of tuberculosis,
      more than 18 years of age were screened for diabetes. Risk factors like age, sex,
      family history of diabetes, alcohol, smoking and obesity were assessed. RESULTS:
      The prevalence of diabetes in tuberculosis patients was found to be 29% (known
      diabetics - 20.7%, new Diabetes cases - 8.3%). Diabetes was significantly
      associated with older age, family history of diabetes, consumption of alcohol and
      sputum positivity. CONCLUSIONS: Screening patients with Tuberculosis for fasting
      blood sugar estimation will help in early detection of diabetes.

PMID- 24678476
TI  - Biliopancreatic Diversion is More Effective Than Sleeve Gastrectomy.

PMID- 24678475
TI  - Comparison of vertical sleeve gastrectomy versus biliopancreatic diversion.
AB  - BACKGROUND: Vertical sleeve gastrectomy (VSG) was originally performed as the
      first-stage of biliopancreatic diversion with duodenal switch (BPD/DS) for
      superobesity as a strategy to reduce perioperative complications and morbidity.
      VSG is now considered a definitive procedure because of its technical simplicity
      and promising outcomes. AIMS: To analyze the outcomes of laparoscopic VSG and to
      compare them with those of single-stage laparoscopic BPD/DS. MATERIALS AND
      METHODS: A retrospective review of 200 consecutive patients who underwent VSG and
      BPD/DS between 2008 and 2011. RESULTS: A total of 100 patients underwent
      laparoscopic VSG and 100 patients underwent laparoscopic BPD/DS. The patients in
      VSG group were older, but gender distribution and body mass index were
      comparable. Mean operative time for VSG was significantly shorter compared with
      that of BPD/DS. A single patient in each groups required open conversion. Staple
      line leak (n = 1) and intraluminal hemorrhage into the newly-created sleeve (n =
      1) occurred in the BPD/DS group. Mean length of stay was shorter after VSG (3.1
      vs. 3.9 days). At 6 months postoperatively, excess weight loss between the two
      groups revealed statistically significant difference, favoring BPD/DS.
      CONCLUSIONS: Despite promising outcomes and technical simplicity of VSG, BPD/DS
      provides significantly superior excess weight loss in morbidly obese patients.

PMID- 24678477
TI  - Evaluation of regression in autism spectrum disorder based on parental reports.
AB  - BACKGROUND: Research indicates that some children with autism spectrum disorder
      (ASD) experience a developmental regression. AIMS: The study examined the
      percentage of children with autism, pervasive developmental disorder (PDD), ASD,
      and Asperger syndrome (AS) who were considered to be delayed (D), regressed (R),
      or delayed and later regressed (DR) and examined any relationship with autism
      severity, time of onset, factors associated with onset, gastrointestinal (GI)
      symptoms, race, age, and gender. MATERIALS AND METHODS: The study reviewed
      developmental and medical information based on parental reports of 135 children
      with a diagnosis of autism, PDD, ASD, or AS. RESULTS: The number of children in
      the D group was 53 (39.2%) with 19 (14.1%) in the DR group and 63 (46.7%) in the
      R group. Thus, 82 children (60.7%) were reported to have R. In regard to onset of
      symptoms, there was a significant difference between the D and R groups as well
      as between the DR and R groups. The analyses showed that there was no significant
      relationship between age, gender, race, severity, or GI symptoms and membership
      in any group; D, DR, or R. The majority of parents reported that the regression
      was preceded by or was associated with vaccinations (57.3%) or another medically
      related event (11.0%). CONCLUSIONS: The findings are consistent with previous
      research and reinforce our understanding of regression in those children with an
      ASD diagnosis.

PMID- 24678478
TI  - The pivotal role of parents in documenting early development.

PMID- 24678479
TI  - Role of Enteric Supplementation of Probiotics on Late-onset Sepsis by Candida
      species in Preterm Low Birth Weight Neonates: A Randomized, Double Blind, Placebo
      controlled Trial.
AB  - BACKGROUND: The increase in invasive fungal infections (IFIs) in neonatal
      intensive care unit (NICU) is jeopardizing the survival of preterm neonates.
      Probiotics modulating the intestinal microflora of preterm neonates may minimize
      enteral fungal colonization. AIMS: This study was to examine whether probiotic
      supplementation in neonates reduced fungal septicemia. MATERIALS AND METHODS:
      This prospective, randomized, double blind trial investigating the
      supplementation of preterm infants with a probiotic was done from May 2012 to
      April 2013, with 112 subjects randomized into two groups. PRIMARY OUTCOME:
      Decreased fungal colonization in gastrointestinal tract. Others: Incidence of
      late onset septicemia; duration of the primary hospital admission; number of days
      until full enteral feeds established. RESULTS: Full feed establishment was
      earlier in probiotics group compared to placebo group (P = 0.016). The duration
      of hospitalization was less in the probiotic group (P = 0.002). Stool fungal
      colonization, an important outcome parameter was 3.03 +/- 2.33 * 10(5) colony
      formation units (CFU) in the probiotics group compared to 3 +/- 1.5 * 10(5) CFU
      in the placebo group (P = 0.03). Fungal infection is less in the study group (P =
      0.001). CONCLUSION: The key features of our study were reduced enteral fungal
      colonization, reduce invasive fungal sepsis, earlier establishment of full
      enteral feeds, and reduced duration of hospital stay in the probiotics group.

PMID- 24678480
TI  - Not all Probiotics are the Same: Gut Microbiota Modulation with a Multistrain
      Probiotics.

PMID- 24678481
TI  - Molecular mechanisms of luteinization.
AB  - Dynamic changes in steroidogenesis occur in ovarian granulosa cells during
      ovulation after the LH surge. The ovulatory LH surge induces rapid up-regulation
      of steroidogenic acute regulatory (StAR) protein and rapid down-regulation of
      aromatase (Cyp19a1) in granulosa cells undergoing luteinization during ovulation.
      These rapid changes in StAR and Cyp19a1 gene expression after the LH surge
      efficiently facilitate progesterone production, which plays a crucial role in
      ovulation and the following luteinization. Recently, it has become clear that
      epigenetic regulation such as histone modifications and DNA methylation play a
      key role in gene expression through the chromatin remodeling of the promoter
      region. This study reports the in vivo evidence that epigenetic mechanisms
      including histone modifications, DNA methylation and chromatin remodeling are
      involved in the rapid changes of StAR and Cyp19a1 gene expression in granulosa
      cells undergoing luteinization during ovulation. 

PMID- 24678482
TI  - Intrauterine therapy for macrocystic congenital cystic adenomatoid malformation
      of the lung.
AB  - OBJECTIVE: To report on our experiences with thoracoamniotic shunting and/or the
      injection of a sclerosing agent (OK-432) to treat fetuses diagnosed with
      macrocystic congenital cystic adenomatoid malformation (CCAM) of the lung.
      METHODS: A retrospective study was undertaken in six fetuses with macrocystic
      CCAM at our institute that had been confirmed by postnatal surgery between August
      1999 and January 2012. RESULTS: Six fetuses that had been diagnosed with
      macrocystic CCAM were analyzed. The median gestational age at diagnosis was 23.5
      weeks (range, 19.5-31.0 weeks), and at the time of primary treatment was 24.0
      weeks (range, 20.5-31.0 weeks). The mean size of the largest cyst at the initial
      assessment was 42.5+/-15 mm. Four fetuses were associated with mediastinal
      shifting, and one also showed fetal hydrops. All fetuses underwent a shunting
      procedure within the cysts, one case among them was also treated with OK-432.
      After the completion of all procedures, the mean size of the largest cyst was all
      decreased (14.2+/-12 mm). The median gestational age at delivery was 38.0 weeks
      (range, 32.4-40.3 weeks). All of the newborns underwent the surgical resection at
      a median age of 6 days (range, 1-136 days) and are currently doing well without
      any complications. CONCLUSION: We suggest that intrauterine decompression therapy
      to manage fetal macrocystic CCAM is recommendable treatment for good perinatal
      outcome.

PMID- 24678483
TI  - Comparison of oxidative stress markers in umbilical cord blood after vaginal and
      cesarean delivery.
AB  - OBJECTIVE: The purpose of our study was to investigate the effect of the mode of
      delivery on the oxidant and antioxidant system in umbilical cord blood. METHODS:
      We performed gas analysis of umbilical venous blood and umbilical arterial blood
      immediately after delivery in 38 women; eighteen women had a vaginal delivery
      while 20 women delivered via cesarean section at over 37 weeks gestation. We
      examined lipid peroxide concentration by thiobarbituric acid reaction, protein
      carbonyl content by 2,4-dinitrophenylhydrazine reaction, and total antioxidant
      capacity by oxygen radical absorbance capacity assay. RESULTS: Lipid peroxide
      levels in umbilical venous blood were significantly higher in patients delivering
      by planned cesarean section (1.81 +/- 0.06 nmol/mg protein) than those with
      vaginal delivery (1.24 +/- 0.05 nmol/mg protein) (P < 0.05). Antioxidant capacity
      in umbilical venous blood was significantly higher in patients delivering by
      planned cesarean section (119.70 +/- 0.13 uM/uL) than those with a vaginal
      delivery (118.70 +/- 0.29 uM/uL) (P < 0.05). There was no significant difference
      in the carbonyl content of umbilical venous blood or in the lipid peroxide,
      carbonyl content, and total antioxidant capacity of umbilical arterial blood.
      CONCLUSION: Lipid peroxidation levels and antioxidant capacity in umbilical
      venous blood were higher in patients delivering by planned cesarean section than
      those with a vaginal delivery. Therefore, we propose that both the mother and
      neonate are exposed to higher oxidative stress during cesarean section delivery.

PMID- 24678484
TI  - Impact of body mass index on the prognosis of Korean women with endometrioid
      adenocarcinoma of the uterus: A cohort study.
AB  - OBJECTIVE: To analyze how pretreatment body mass index relates to known
      endometrial cancer prognostic factors and how it impacts the disease-free
      survival and cause-specific survival of Korean women with endometrial cancer.
      METHODS: The patients were divided into the non-obese (<25 kg/m(2)) and obese
      groups (>=25 kg/m(2)) according to their pretreatment body mass index. The 25
      kg/m(2) body mass index cut-off was based on the World Health Organization
      criteria for Asian people. The two groups were compared in terms of their
      clinicopathological characteristics and survival outcomes. RESULTS: A total of
      213 consecutive patients with endometrioid adenocarcinoma of the uterus met the
      eligibility criteria of this study and were included in the analysis. Of these
      patients, 105 patients had a body mass index less than 25 kg/m(2) (non-obese
      group) and 108 patients had a body mass index equal to or more than 25 kg/m(2)
      (obese group). The two groups did not differ in terms of age, menopause, parity,
      height, FIGO (International Federation of Obstetrics and Gynecology) stage, tumor
      grade, tumor size, myometrial invasion, lymphovascular space invasion, cytology,
      and lymph node metastasis. Body mass index was not a significant factor for
      disease-free and cause-specific survival in univariate analysis, and after
      adjusting for all prognostic factors that were significant in univariate
      analysis, it did not associate significantly with disease-free and cause-specific
      survival. CONCLUSION: In Korean women with endometrioid adenocarcinoma of the
      uterus, a high pretreatment body mass index did not associate with other
      prognostic factors and had little impact on the disease-free survival and cause
      specific survival of these women.

PMID- 24678485
TI  - Surgical impact on serum anti-Mullerian hormone in women with benign ovarian
      cyst: A prospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate the surgical impact of benign
      ovarian mass on ovarian reserve as measured by serum follicle stimulating hormone
      (FSH), estradiol (E2) and anti-Mullerian hormone (AMH) levels, antral follicle
      count (AFC) and ovarian volumes. In addition, the differences in ovarian reserve
      impairment between endometrioma cystectomy and non-endometrioma cystectomy were
      investigated. METHODS: In this prospective study, 22 patients of reproductive age
      (range, 18.35 years) with benign ovarian masses were enrolled to undergo
      laparoscopic cystectomy. Of whom 12 had endometriomas and 10 had non
      endometriomas. On early follicular phase (day 3) of the cycle preceding the
      operation and three months after the laparoscopic cystectomy, serum levels of
      FSH, E2 and AMH, AFC and ovarian volumes were measured in all patients. Data were
      analyzed with Mann-Whitney U-test and Wilcoxon rank test using SPSS ver. 12.0 for
      statistic analysis. RESULTS: Median level of serum AMH was significantly
      decreased from 5.48 ng/mL (interquartile range [IQR], 2.80-7.47) before
      cystectomy to 2.56 ng/mL (IQR, 1.74-4.32) 3 months postoperation (P<0.05). On the
      other hand, no significant differences in FSH, E2, AFC and ovarian volumes were
      found between the preoperative and three months postoperative levels. In a
      subgroup analysis of the pathologic type of the ovarian cyst, postoperative serum
      AMH levels were significantly decreased in the endometrioma group, but not in the
      non-endometrioma group. CONCLUSION: Serum AMH levels were significantly decreased
      after laparoscopic cystectomy without any changes of other ovarian reserve tests.

PMID- 24678486
TI  - Laparoscopic assisted adenomyomectomy using double flap method.
AB  - OBJECTIVE: The purpose of this study was to evaluate postoperative prognosis and
      progression in patients who received laparoscopic-assisted adenomyomectomy using
      the double flap method. METHODS: The pelvic cavity was explored by the
      conventional laparoscopic method, and drainage was achieved through a 5-mm
      trocar. After a small incision in the abdomen, the uterus was incised from the
      fundus to the upper cervical margin until exposing the endometrial cavity.
      Adenomyotic tissue was removed using a scalpel, scissors, or monopolar electrical
      bovie. The endometrial cavity was repaired with interrupted sutures using 2-0
      vicryl. One side of the serosal flap was used to cover the endometrial side of
      the uterus. The second serosal flap covered the first flap after removal of the
      serosal surface of the first flap. RESULTS: From January 2008 to March 2012,
      there were 11 cases of laparoscopic-assisted adenomyomectomy at Chungnam National
      University Hospital. Nine cases were analyzed, excluding two cases with less than
      one year of follow-up. The average patient age was 37.0 years and average follow
      up duration was 32.8 months. All patients showed improvement in dysmenorrhea (P <
      0.001) and hypermenorrhea (P = 0.001) after surgery and were evaluated by visual
      analogue scale score. However, symptoms of adenomyosis were aggravated in three
      patients. Adenomyosis was progressed in the side opposite the site of operation.
      One patient required a total laparoscopic hysterectomy 27 months after surgery.
      CONCLUSION: Laparoscopic-assisted adenomyomectomy using the double flap method is
      effective for uterine reduction and relief of dysmenorrhea and hypermenorrhea.
      Conservative management and careful follow-up are needed because adenomyosis can
      recur or progress in some patients.

PMID- 24678487
TI  - Evaluation of risk factors of vaginal cuff dehiscence after hysterectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate risk factors of vaginal cuff
      dehiscence or evisceration according to the type of operation. METHODS: Medical
      records of 604 women who underwent hysterectomies at Korea University Anam
      Hospital between June 2007 and June 2011 were reviewed. They were allocated to
      six groups. The six types of hysterectomies included robotic hysterectomy (n =
      7), robotic radical hysterectomy and node dissection (RRHND, n = 9), total
      laparoscopic hysterectomy (TLH, n = 274), laparoscopy assisted vaginal
      hysterectomy (LAVH, n = 238), laparoscopic radical hysterectomy and node
      dissection (n = 11), and abdominal radical hysterectomy (ARH, n = 63). The
      characteristics and outcomes of each groups were compared. RESULTS: There was no
      difference in the characteristics of patients between 6 groups. In total of 604
      hysterectomies, 3 evisceration (0.49%) and 21 dehiscences (3.47%) occurred.
      Evisceration were found in RRHND (1/9, 11.1%), TLH (1/276, 0.36%), and ARH (1/63,
      1.56%). Dehiscences occurred in TLH (15/274, 5.42%), LAVH (4/238, 1.68%), and ARH
      (2/63, 3.17%). In 169 cases of TLH with intra-corporeal continuous suture, 1
      evisceration and 4 dehiscences occurred, whereas 11 dehiscences occurred in 105
      TLH cases with vaginal continuous locking suture (2.96% vs. 10.47%, P = 0.02).
      CONCLUSION: The incidence of vaginal cuff dehiscenceand eviscerationwas
      significantly higher in TLH than LAVH. The intra-corporeal cuff suture was
      superior to the vaginal suture to prevent the vaginal cuff complications in TLH.

PMID- 24678488
TI  - Comparison of estrogen receptor-alpha, progesterone receptor and calponin
      expression in gonadotrophin-releasing hormone agonist-sensitive and -resistant
      uterine fibroids.
AB  - OBJECTIVE: This study was aimed to compare immunohistochemical expression of
      estrogen receptor (ER)-alpha, progesterone receptor (PR), and calponin in
      gonadotrophin-releasing hormone agonist (GnRH-a)-sensitive and -resistant uterine
      fibroids. METHODS: We collected data retrospectively. The sensitive group
      consisted of women who had reduction in uterine volume greater than 40% following
      GnRH-a treatment. Uterine volume was either reduced by less than 10%, or was
      increased in the resistant group. A tissue microarray was constructed using
      formalin-fixed, paraffin-embedded tissues, 31 and 26 patients for the sensitive
      and resistant groups, respectively. Tissue sections were immunostained with
      antibodies against ER-alpha, PR, and calponin. The intensity and area of the
      immunohistochemical reactions were evaluated using a semi-quantitative scoring
      system. The Mann-Whitney U-test, Fisher's exact test, and Spearman's rank
      correlation test were used for analysis of data. RESULTS: PR (P = 0.04) and
      calponin (P = 0.03) showed a significantly higher staining intensity in the
      resistant group than in the sensitive group. Both groups showed comparable
      expression of ER-alpha (P = 0.23). In correlation analysis between changes in
      uterine volume after GnRH-a therapy and clinicopathological factors, the
      immunohistochemical intensity of PR (P = 0.04) and calponin (P = 0.03) was
      significantly correlated with changes in uterine volume. CONCLUSION: This study
      shows that GnRH-a resistance of uterine fibroids is not related to ER-alpha
      content, but the expression of PR and calponin is related with GnRH-a resistance.

PMID- 24678489
TI  - Thanatophoric dysplasia in a dichorionic twin confirmed by genetic analysis at
      the early second trimester: A case report and literature review.
AB  - Thanatophoric dysplasia (TD) is caused by mutation of the gene that encodes
      fibroblast growth factor 3 (FGFR3). Owing to the poor prognosis for TD, prenatal
      diagnosis is critical to optimal perinatal management. We report here a case of
      TD in twin pregnancy, which was prenatally diagnosed by DNA analysis following
      amniocentesis at 15 weeks, and was managed by selective fetal termination.
      Prenatal ultrasonography and molecular analysis to detect TD-specific mutations
      enable accurate diagnosis of FGFR3-related TD in utero and appropriate
      obstetrical management at early gestation during twin pregnancy. 

PMID- 24678490
TI  - Arteriovenous malformation in uterine cervix during pregnancy.
AB  - As the development of Doppler ultrasonography, many cases of uterine
      arteriovenous malformation (AVM) have beed diagnosed. But there is no case of
      cervical AVM in pregnant uterus. We present a 33-year-old pregnant woman who was
      diagnosed with AVM of the uterine cervix during the midtrimester. Color Doppler
      sonography and magnetic resonance image were used for diagnosis. We performed
      Cesarean section because of the risk of massive bleeding from the cervical AVM at
      34 weeks' gestation. This is the first case of cervical AVM during pregnancy with
      a successful outcome and an uneventful postpartum course. 

PMID- 24678491
TI  - Successful laparoscopic surgery for 14-month-old infant with ovarian torsion.
AB  - The prevalence of ovarian torsion is 4.9 among 100,000 females between ages 1 to
      20 years. The diagnosis of ovarian torsion in children, especially in infants, is
      very difficult. Since they cannot explain related symptoms accurately, and
      reproductive organs lie high in the abdomen, physical examination shows unclear
      findings. For these reasons, we use imaging studies, such as ultrasonography and
      magnetic resonance imaging, to diagnose ovarian torsion. However, it is of
      limited value to diagnose by using these modalities alone. Therefore, clinical
      suspicion is important for diagnosis. Though pediatric laparoscopic surgery was
      introduced 20 years ago, it has been widely performed since the mid 1990s with
      the development of 3-mm instruments. In addition, usually the pediatric operation
      is done in the pediatric surgery office, even though it is a gynecologic
      procedure. In addition, laparotomy is still more frequently conducted in current
      clinical practice, although the frequency of laparoscopic surgery has increased.
      However, it is thought that expert gynecologic surgeons can perform pediatric
      laparoscopic operations if they pay attention to some precautions. We report
      herein the case of a 14-month-old infant who underwent emergency laparoscopic
      untwisting of ovarian torsion successfully without complications by a gynecologic
      surgeon, with a brief review of the literature. 

PMID- 24678492
TI  - Aggressive angiomyxoma of the vulva: A case report.
AB  - Aggressive angiomyxoma (AA) is an unusual mesenchymal tumor. AA occurs most
      commonly in women of reproductive age and is located in the perineal or pelvic
      region. This is a distinct soft tissue tumor that has a prominent myxoid matrix
      and numerous thin-walled blood vessels and may have an aggressive local
      recurrence. The tumors have the characteristics of large size (usually greater
      than 10 cm) and slow growth, and are not painful. The standard treatment for AA
      is total excision and close follow-up. We announce a case of a 35 year-old female
      presenting with a pedunculated AA on the right labium majora that has not
      relapsed for seven years. 

PMID- 24678493
TI  - A case of vulvar hematoma with rupture of pseudoaneurysm of pudendal artery.
AB  - Vulvar hematomas are uncommon outside of the obstetric population and may be the
      result of trauma to the perineum. Vulvar hematomas most often present with low
      abdominal pain and urologic and neurologic symptoms. The vulva has rich
      vascularization that is supplied by the pudendal artery, a branch of the anterior
      division of the internal iliac artery. We describe a rare case of a 15-cm-sized
      vulvar hematoma with the suggested rupture of a pseudoaneurysm of the left
      pudendal artery without trauma injury. A 14-year-old girl presented with sudden
      pain and swelling in her left labium and was successfully treated with selective
      arterial embolization and surgical evacuation. We provide a literature review and
      discuss patient treatment and management strategies. 

PMID- 24678494
TI  - Inguinal endometriosis in a patient without a previous history of gynecologic
      surgery.
AB  - Endometriosis, defined as growth of endometrial stroma and glands outside the
      uterine cavity, is a chronic and recurrent disease that affects patients' quality
      of life. Ectopic endometrial tissue can proliferate at any location in the body,
      but the pelvic organs and peritoneum are the most frequent implantation sites.
      Among extrapelvic endometriosis, inguinal endometriosis is a very rare
      gynecologic condition usually associated with previous pelvic surgery.
      Endometriosis should be preoperatively distinguished from other inguinal masses
      using computed tomography, magnetic resonance imaging, or ultrasonography. Here,
      we report a case of right inguinal endometriosis in a patient with no previous
      history of gynecologic surgery; in addition, we have provided a brief review of
      relevant literature. 

PMID- 24678495
TI  - A case of cystic adenomyoma of the uterus after complete abortion without
      transcervical curettage.
AB  - We diagnosed a 2-cm, large cystic adenomyoma after complete abortion without
      transcervical curettage, based on symptoms of dysmenorrhea, time of onset, and
      sonographic findings. The cystic adenomyoma was treated successfully with
      laparoscopic mass excision. 

PMID- 24678497
TI  - Rejuvenation.

PMID- 24678498
TI  - Treadmill exercise improves short-term memory by enhancing neurogenesis in
      amyloid beta-induced Alzheimer disease rats.
AB  - Alzheimer's disease is one of the most devastating neurodegenerative disorders,
      and this disease is characterized by severe memory impairment and decline of
      cognition. Hippocampal neurons are vulnerable to injury induced by Alzheimer's
      disease. Physical exercise is known to promote cell survival and functional
      recovery after brain injuries. In the present study, we investigated the effects
      of treadmill exercise on short-term memory in relation with neurogenesis in the
      rats with amyloid beta25-35 (Abeta25-35)-induced Alzheimer's disease. The rat
      model of Alzheimer's disease was induced by the intracerebroventricular (ICV)
      injection of Abeta25-35, using a stereotaxic instrument. The rats in the exercise
      group were forced to run on a treadmill for 30 min once daily for 4 consecutive
      weeks, starting 2 days after Abeta25-35 injection. Presently, short-term memory
      was deteriorated and apical dendritic length in the hippocampus was shortened in
      the hippocampus by Abeta25-35 injection. In contrast, treadmill exercise
      alleviated memory impairment and increased apical dendritic length in the Abeta25
      35-injected rats. Neurogenesis and brain-derived neurotorphic factor (BDNF) and
      tyrosine kinase B (trkB) in the hippocampal dentate gyrus were decreased by
      Abeta25-35 injection. Treadmill exercise increased neurogenesis and expressions
      of BDNF and trkB expressions. The present study shows that treadmill exercise may
      provide therapeutic value for the alleviating symptoms of Alzheimer's disease. 

PMID- 24678499
TI  - Effects of endurance exercise on expressions of glial fibrillary acidic protein
      and myelin basic protein in developing rats with maternal infection-induced
      cerebral palsy.
AB  - Periventricular leukomalacia (PVL) is a common white matter lesion affecting the
      neonatal brain. PVL is closely associated with cerebral palsy (CP) and
      characterized by increase in the number of astrocytes, which can be detected by
      positivity for glial fibrillary acidic protein (GFAP). Change in myelin basic
      protein (MBP) is an early sign of white matter abnormality. Maternal or placental
      infection can damage the neonatal brain. In the present study, we investigated
      the effects of treadmill walking exercise on GFAP and MBP expressions in rats
      with maternal lipopolysaccharide (LPS)-induced PVL. Immunohistochemistry was
      performed for the detection of GFAP and MBP. The present results showed that
      intracervical maternal LPS injection during pregnancy increased GFAP expression
      in the striatum and decreased MBP expression in the corpus callosum of rats. The
      results also showed that treadmill walking exercise suppressed GFAP expression
      and enhanced MBP expression in the brains of rats with maternal LPS-induced PVL.
      The present study revealed that treadmill walking exercise is effective for the
      suppressing astrogliosis and hypomyelination associated with PVL. Here in this
      study, we showed that treadmill walking exercise may be effective therapeutic
      strategy for alleviating the detrimental effects of CP. 

PMID- 24678500
TI  - Treadmill exercise enhances NMDA receptor expression in schizophrenia mice.
AB  - Schizophrenia is a serious psychiatric disorder with several symptoms including
      cognitive dysfunction. Although the causes of schizophrenia are still unclear,
      there is a strong suspicion that the abnormality in N-methyl-D-aspartate (NMDA)
      receptor may contribute to schizophrenia symptoms. In the present study, the
      effect of treadmill exercise on the NMDA receptor expression was evaluated using
      MK-801-induced schizophrenia mice. Immunohistochemistry for expressions of NMDA
      receptor tyrosine hydroxylase (TH) was conducted. Western blot for brain-derived
      neurotrophic factor (BDNF) was also performed. In the present results, the mice
      in the MK-801-treated group displayed reduced NMDA receptor expression. Enhanced
      TH expression and suppressed BDNF expression were also observed in the MK-801
      treated mice. Treadmill exercise improved NMDA receptor expression in the MK-801
      induced schizophrenia mice. Treadmill exercise also suppressed TH expression and
      enhanced BDNF expression in the MK-801-induced schizophrenia mice. The present
      study showed that down-regulation of NMDA receptor demonstrated schizophrenia
      like parameters, meanwhile treadmill running improved schizophrenia-related
      parameters through enhancing NMDA receptor expression. 

PMID- 24678501
TI  - Treadmill exercise ameliorates symptoms of attention deficit/hyperactivity
      disorder through reducing Purkinje cell loss and astrocytic reaction in
      spontaneous hypertensive rats.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder of
      cognition. We investigated the effects of treadmill exercise on Purkinje cell and
      astrocytic reaction in the cerebellum of the ADHD rat. Adult male spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto rats (WKYR) weighing 210+/- 10 g were
      used. The animals were randomly divided into four groups (n= 15): control group,
      ADHD group, ADHD and methylphenidate (MPH)-treated group, ADHD and treadmill
      exercise group. The rats in the MPH-treated group as a positive control received
      1 mg/kg MPH orally once a day for 28 consecutive days. The rats in the treadmill
      exercise group were made to run on a treadmill for 30 min once a day for 28 days.
      Motor coordination and balance were determined by vertical pole test.
      Immunohistochemistry for the expression of calbindinD-28 and glial fibrillary
      acidic protein (GFAP) in the cerebellar vermis and Western blot for GFAP, Bax,
      and Bcl-2 were conducted. In the present results, ADHD significantly decreased
      balance and the number of calbindin-positive cells, while GFAP expression and
      Bax/Bcl-2 ratio in the cerebellum were significantly increased in the ADHD group
      compared to the control group (P< 0.05, respectively). In contrast, treadmill
      exercise and MPH alleviated the ADHD-induced the decrease of balance and the
      number of calbindine-positive cells, and the increase of GFAP expression and
      Bax/Bcl-2 ratio in the cerebellum (P< 0.05, respectively). Therefore, the present
      results suggested that treadmill exercise might exert ameliorating effect on ADHD
      through reduction of Purkinje cell loss and astrocytic reaction in the
      cerebellum. 

PMID- 24678502
TI  - Effects of rehabilitative horse riding on the Sit-to-Stand action of the
      adolescent with brain lesions.
AB  - The purpose of this study was to investigate the balance abilities of the
      adolescent girl with brain lesions by Sit-to-Stand (STS) action analysis before
      and after the rehabilitative horse riding of 16 week program. The subject aged 16
      yr old who had the disabilities of spasticity and hemiplegia was recruited with
      the consent approval. The equilibrium abilities of the subject were tested by Sit
      to-Stand examination with Weight Transfer Time (WTT), Mean Rising Index (MRI),
      Mean Weight Asymmetry (MWA), Max Trunk Flexion Velocity (MTFV), and Max Trunk
      Extension Velocity (MTEV). Research was designed by AB single subject study with
      baseline of 3 times of measurement and rehabilitative horse riding treatments. In
      the results, the enhancement of the subject's equilibrium ability was shown from
      the comparisons between baseline and treatment by the STS test that WTT was 2.37
      sec faster, MRI was 6.64 N/kg higher, and MWA was 8.12% lower, and MTFV was 0.57
      degrees /sec larger than all those means of baseline. It suggested that the
      subject showed her enhanced balance ability while in sitting and standing after
      the rehabilitative horse riding treatments. 

PMID- 24678503
TI  - A 12-week rehabilitation program improves body composition, pain sensation, and
      internal/external torques of baseball pitchers with shoulder impingement symptom.
AB  - The aim of this study was to investigate the effects of a 12-week rehabilitation
      program on body composition, shoulder pain, and isokinetic internal/external
      torques of pitchers with impingement syndrome. A total of 30 pitchers were
      divided into 2 groups: experimental group (EG, n = 16) and control group (CG, n=
      14). The rehabilitation program consisted of physical therapy, warm-up, work-out,
      and cool-down. As results, body weight and fat mass of EG were decreased whereas
      muscle mass of EG was significantly increased after the experiment. The pain
      degrees in resting, normal daily activity, and strenuous activity on the numeric
      pain rating scale were significantly decreased in the EG. The internal and
      external peak torques (PTs) of uninvolved and involved sides of EG were increased
      in EG after 12 weeks. Such results provide a deficit ratio of both sides in EG
      close to normal values. The ratios of internal/external PTs in EG were also close
      to the reference values. The internal and external total works of both sides in
      EG were similar to the values of PT. The fatigue indices of internal and external
      rotators of both sides in EG were decreased. As a conclusion, a 12-week
      rehabilitation program reduced the shoulder pain, improved the body composition
      and enhanced the isokinetic shoulder internal/external rotators in EG with
      impingement symptoms. Also the study suggested that the rehabilitation program
      evened out the ratio between internal and external rotators and lowered the
      fatigue level after the experiment. 

PMID- 24678504
TI  - Factors influencing physical activity in older adults.
AB  - The purpose of this study was to investigate the extent to which Korean seniors
      report employing different motivational and social cognitive strategies related
      to physical activity, and to evaluate which motivational and social cognitive
      strategies were related to physical activity, and which motivational and social
      cognitive strategies differentiate between high active and low-active Korean
      seniors. Community-dwelling older adults (N = 187) participated in the study and
      completed questionnaires assessing self-reported physical activity and a range of
      motivational and social cognitive variables. The results showed that physical
      activity was predicted by quality goal-setting practices, self-efficacy, social
      support from family and physical activity self-regulation subscales of social
      support and exercise planning and scheduling. Between the groups of highly
      physically active and low-active participants, we observed differences in
      satisfaction with life, self-efficacy, quality goal-setting practices, and self
      regulatory strategies related to self-monitoring, goal-setting, social support
      and time management. In conclusion, these findings indicate that physical
      activity promotion efforts among Korean older adults should focus on enhancing
      self-efficacy, social support, and self-regulation skills. 

PMID- 24678505
TI  - Sparse representation for tumor classification based on feature extraction using
      latent low-rank representation.
AB  - Accurate tumor classification is crucial to the proper treatment of cancer. To
      now, sparse representation (SR) has shown its great performance for tumor
      classification. This paper conceives a new SR-based method for tumor
      classification by using gene expression data. In the proposed method, we firstly
      use latent low-rank representation for extracting salient features and removing
      noise from the original samples data. Then we use sparse representation
      classifier (SRC) to build tumor classification model. The experimental results on
      several real-world data sets show that our method is more efficient and more
      effective than the previous classification methods including SVM, SRC, and LASSO.

PMID- 24678506
TI  - D-glucosamine promotes transfection efficiency during electroporation.
AB  - D-Glucosamine is a useful medicament in various fields of medicine and dentistry.
      With respect to stability of the cell membrane, it has been reported that
      bradykinin-induced nociceptive responses are significantly suppressed by the
      direct application of D-glucosamine. Electroporation is usually used to
      effectively introduce foreign genes into tissue culture cells. Buffers for
      electroporation with or without D-glucosamine are used in experiments of
      transfection vectors. This is the first study to indirectly observe the stability
      and protection of the osteoblast membrane against both electric stress and gene
      uptake (the proton sponge hypothesis: osmotic rupture during endosomes prior to
      fusion with lysosomes) in electroporation with D-glucosamine application. The
      transfection efficiency was evaluated as the fluorescence intensity of the
      transfected green fluorescent protein (GFP) in the cultured cells (osteoblasts;
      NOS-1 cells). The transfection efficiency increased over 30% in the
      electroporation samples treated with D-glucosamine-supplemented buffer after one
      day. The membrane absorption of D-glucosamine is the primary mechanism of
      membrane stress induced by electric stress. This new function of D-glucosamine is
      useful and meaningful for developing more effective transformation procedures. 

PMID- 24678507
TI  - Characterization of H3PO4-treated rice husk adsorbent and adsorption of
      copper(II) from aqueous solution.
AB  - Rice husk, a surplus agricultural byproduct, was applied to the sorption of
      copper from aqueous solutions. Chemical modifications by treating rice husk with
      H3PO4 increased the sorption ability of rice husk for Cu(II). This work
      investigated the sorption characteristics for Cu(II) and examined the optimum
      conditions of the sorption processes. The elemental compositions of native rice
      husk and H3PO4-treated rice husk were determined by X-ray fluorescence (XRF)
      analysis. The scanning electron microscopic (SEM) analysis was carried out for
      structural and morphological characteristics of H3PO4-treated rice husk. The
      surface functional groups (i.e., carbonyl, carboxyl, and hydroxyl) of adsorbent
      were examined by Fourier Transform Infrared Technique (FT-IR) and contributed to
      the adsorption for Cu(II). Adsorption isotherm experiments were carried out at
      room temperature and the data obtained from batch studies fitted well with the
      Langmuir and Freundlich models with R (2) of 0.999 and 0.9303, respectively. The
      maximum sorption amount was 17.0358 mg/g at a dosage of 2 g/L after 180 min. The
      results showed that optimum pH was attained at pH 4.0. The equilibrium data was
      well represented by the pseudo-second-order kinetics. The percentage removal for
      Cu(II) approached equilibrium at 180 min with 88.9% removal.

PMID- 24678508
TI  - Female gender and acne disease are jointly and independently associated with the
      risk of major depression and suicide: a national population-based study.
AB  - Acne is a common disease in adolescence with female preponderance. It could cause
      poor self-esteem and social phobia. Previous studies based on questionnaires from
      several thousands of adolescents showed that acne is associated with major
      depression and suicide. However, the gender- and age-specific risk of depression
      and suicide in patients with acne remain largely unknown. Using a database from
      the National Health Insurance, which included 98% of the population of Taiwan in
      2006, we identified patients of acne, major depression, and suicide based on ICD
      9-CM codes. Totally 47111 patients with acne were identified (16568 males and
      30543 females) from 1 million subjects. The youths of 7-12 years had the highest
      prevalence of acne (14.39%). Major depression was more common in those with acne
      (0.77%) than controls (0.56% , P < 0.0001) regardless of gender. Multiple
      logistic regression showed an increased risk of major depression in women without
      acne (OR = 1.85, 95% CI 1.75-1.96). The risk is additive in women with acne (OR =
      2.78, 95% CI 2.43-3.17). Similar additive risk of suicide was noticed in women
      with acne. In conclusion, acne and gender, independently and jointly, are
      associated with major depression and suicide. Special medical support should be
      warranted in females with acne for the risk of major depression and suicide. 

PMID- 24678509
TI  - Booster vaccination: the role of reduced antigen content vaccines as a preschool
      booster.
AB  - The need for boosters for tetanus, diphtheria, pertussis, and polio, starting
      from preschool age, is related to the waning immune protection conferred by
      vaccination, the elimination/reduction of natural boosters due to large-scale
      immunization programs, and the possibility of reintroduction of wild agents from
      endemic areas. Taking into account the relevance of safety/tolerability in the
      compliance with vaccination among the population, it have been assessed whether
      today enough scientific evidences are available to support the use of dTap-IPV
      booster in preschool age. The review of the literature was conducted using the
      PubMed search engine. A total of 41 works has been selected; besides, the
      documentation produced by the World Health Organization, the European Centre for
      Disease Control, and the Italian Ministry of Health has been consulted. Many
      recent papers confirm the opportunity to use a low antigenic dose vaccine
      starting from 4 to 6 years of age. There is also evidence that 10 years after
      immunization the rate of seroprotected subjects against diphtheria does not
      differ significantly between those vaccinated with paediatric dose (DTaP) or
      reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for
      diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1
      schedules). 

PMID- 24678510
TI  - Hemodynamic and tubular changes induced by contrast media.
AB  - The incidence of acute kidney injury induced by contrast media (CI-AKI) is the
      third cause of AKI in hospitalized patients. Contrast media cause relevant
      alterations both in renal hemodynamics and in renal tubular cell function that
      lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main
      hemodynamic change induced by contrast media; the vasoconstriction is accompanied
      by a cascade of events leading to ischemia and reduction of glomerular filtration
      rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with
      consequent formation of casts and worsening of ischemia. There is an interplay
      between the negative effects of contrast media on renal hemodynamics and on
      tubular cell function that leads to activation of renin-angiotensin system and
      increased production of reactive oxygen species (ROS) within the kidney.
      Production of ROS intensifies cellular hypoxia through endothelial dysfunction
      and alteration of mechanisms regulating tubular cells transport. The
      physiochemical characteristics of contrast media play a critical role in the
      incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low
      osmolar contrast media rather than high-osmolar contrast media particularly in
      patients at increased risk of CI-AKI. Older age, presence of atherosclerosis,
      congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics
      may multiply the risk of CI-AKI. 

PMID- 24678512
TI  - The use of Hibiscus esculentus (Okra) gum in sustaining the release of
      propranolol hydrochloride in a solid oral dosage form.
AB  - The effectiveness of Okra gum in sustaining the release of propranolol
      hydrochloride in a tablet was studied. Okra gum was extracted from the pods of
      Hibiscus esculentus using acetone as a drying agent. Dried Okra gum was made into
      powder form and its physical and chemical characteristics such as solubility, pH,
      moisture content, viscosity, morphology study using SEM, infrared study using
      FTIR, crystallinity study using XRD, and thermal study using DSC and TGA were
      carried out. The powder was used in the preparation of tablet using granulation
      and compression methods. Propranolol hydrochloride was used as a model drug and
      the activity of Okra gum as a binder was compared by preparing tablets using a
      synthetic and a semisynthetic binder which are hydroxylmethylpropyl cellulose
      (HPMC) and sodium alginate, respectively. Evaluation of drug release kinetics
      that was attained from dissolution studies showed that Okra gum retarded the
      release up to 24 hours and exhibited the longest release as compared to HPMC and
      sodium alginate. The tensile and crushing strength of tablets was also evaluated
      by conducting hardness and friability tests. Okra gum was observed to produce
      tablets with the highest hardness value and lowest friability. Hence, Okra gum
      was testified as an effective adjuvant to produce favourable sustained release
      tablets with strong tensile and crushing strength. 

PMID- 24678511
TI  - NF-kappaB mediated regulation of adult hippocampal neurogenesis: relevance to
      mood disorders and antidepressant activity.
AB  - Adult hippocampal neurogenesis is a peculiar form of process of neuroplasticity
      that in recent years has gained great attention for its potential implication in
      cognition and in emotional behavior in physiological conditions. Moreover, a vast
      array of experimental studies suggested that adult hippocampal neurogenesis may
      be altered in various neuropsychiatric disorders, including major depression,
      where its disregulation may contribute to cognitive impairment and/or emotional
      aspects associated with those diseases. An intriguing area of interest is the
      potential influence of drugs on adult neurogenesis. In particular, several
      psychoactive drugs, including antidepressants, were shown to positively modulate
      adult hippocampal neurogenesis. Among molecules which could regulate adult
      hippocampal neurogenesis the NF- kappa B family of transcription factors has been
      receiving particular attention from our and other laboratories. Herein we review
      recent data supporting the involvement of NF- kappa B signaling pathways in the
      regulation of adult neurogenesis and in the effects of drugs that are endowed
      with proneurogenic and antidepressant activity. The potential implications of
      these findings on our current understanding of the process of adult neurogenesis
      in physiological and pathological conditions and on the search for novel
      antidepressants are also discussed. 

PMID- 24678513
TI  - SNP rs8099917 in gene IL28B might be associated with risk of chronic infection by
      HCV but not with response to treatment.
AB  - AIM: The aim of this study was to characterize the genetic profile of patients
      with chronic hepatitis C virus (HCV) infection relative to polymorphisms
      rs12979860 and rs8099917 in gene IL28B and the association of those polymorphisms
      with the response to treatment with pegylated interferon and ribavirin, performed
      at a reference center in Brazilian Amazonia. METHODS: A total of 75 individuals
      with chronic hepatitis C and 98 healthy individuals from both genders over 18
      years old were assessed. DNA samples were collected from leukocytes and subjected
      to real-time polymerase chain reaction to genotype polymorphisms rs12979860 and
      rs8099917. RESULTS: Analysis of the allelic and genotypic frequencies of the
      investigated polymorphisms showed that both groups were in Hardy-Weinberg
      equilibrium; polymorphism rs12979860 exhibited no significant difference between
      the groups. For polymorphism rs8099917, allele T was significantly less frequent
      (P = 0.0195) among the patients (63.3%) than the controls (75.5%), and the
      patients were 1.7 times as likely to exhibit allele G. No difference in response
      to treatment was associated with SNP patterns. CONCLUSION: The results suggest a
      possible association of SNP rs8099917 with higher odds of chronic HCV infection
      but do not indicate a putative influence of the investigated SNPs on the
      sustained virologic response.

PMID- 24678515
TI  - Technical advancement of radiation therapy.

PMID- 24678516
TI  - Predicting In-Hospital Mortality of ICU Patients: The PhysioNet/Computing in
      Cardiology Challenge 2012.
AB  - Acuity scores, such as APACHE, SAPS, MPM, and SOFA, are widely used to account
      for population differences in studies aiming to compare how medications, care
      guidelines, surgery, and other interventions impact mortality in Intensive Care
      Unit (ICU) patients. By contrast, the focus of the PhysioNet/CinC Challenge 2012
      is to develop methods for patient-specific prediction of in-hospital mortality.
      The data used for the challenge consisted of 5 general descriptors and 36 time
      series (measurements of vital signs and laboratory results) from the first 48
      hours of the first available ICU stay of 12,000 adult patients from the MIMIC II
      database. The challenge was organized as two events: event 1 measured performance
      of a binary classifier, and event 2 measured performance of a risk estimator. The
      score of event 1 was the lower of sensitivity and positive predictive value. The
      score for event 2 was a range-normalized Hosmer-Lemeshow statistic. A baseline
      algorithm (using SAPS-1) obtained event 1 and 2 scores of 0.3125 and 68.58
      respectively. Most participants submitted entries that outperformed the baseline
      algorithm. The top final scores for events 1 and 2 were 0.5353 and 17.88
      respectively.

PMID- 24678514
TI  - Comparative biomechanical and microstructural analysis of native versus peracetic
      acid-ethanol treated cancellous bone graft.
AB  - Bone transplantation is frequently used for the treatment of large osseous
      defects. The availability of autologous bone grafts as the current biological
      gold standard is limited and there is a risk of donor site morbidity. Allogenic
      bone grafts are an appealing alternative, but disinfection should be considered
      to reduce transmission of infection disorders. Peracetic acid-ethanol (PE)
      treatment has been proven reliable and effective for disinfection of human bone
      allografts. The purpose of this study was to evaluate the effects of PE treatment
      on the biomechanical properties and microstructure of cancellous bone grafts
      (CBG). Forty-eight human CBG cylinders were either treated by PE or frozen at -20
      degrees C and subjected to compression testing and histological and scanning
      electron microscopy (SEM) analysis. The levels of compressive strength, stiffness
      (Young's modulus), and fracture energy were significantly decreased upon PE
      treatment by 54%, 59%, and 36%, respectively. Furthermore, PE-treated CBG
      demonstrated a 42% increase in ultimate strain. SEM revealed a modified
      microstructure of CBG with an exposed collagen fiber network after PE treatment.
      We conclude that the observed reduced compressive strength and reduced stiffness
      may be beneficial during tissue remodeling thereby explaining the excellent
      clinical performance of PE-treated CBG.

PMID- 24678518
TI  - A review on amperometric-type immunosensors based on screen-printed electrodes.
AB  - In this brief review, we summarize the recent research activities involved in the
      development of amperometric-type immunosensors based on screen-printed electrodes
      (SPEs). We focus on the underlying principle involved in these types of sensors,
      their fabrication and electrode surface modification. We also discuss the various
      factors involved in the designing of such immunosensors and how they affect their
      performances. Finally we provide an insight into the drawbacks associated with
      these SPEs. 

PMID- 24678519
TI  - Nicardipine and preterm labour: pulmonary oedema.

PMID- 24678520
TI  - Toxic epidermal necrolysis and related syndromes: a Spanish pharmacovigilance
      review.

PMID- 24678521
TI  - "Grastims" and fatal capillary leak syndrome.

PMID- 24678522
TI  - Pregnant women are still exposed to acitretin.

PMID- 24678523
TI  - Response to Sympathoinhibitory effect of diltiazem and prevention of aneurysm
      formation.

PMID- 24678524
TI  - Response to Effect of serum chloride on mortality in hypertensive patients.

PMID- 24678525
TI  - Response to Prostaglandin E2 mediates connecting tubule glomerular feedback.

PMID- 24678526
TI  - Laparoscopic ventral rectopexy is effective for solitary rectal ulcer syndrome
      when associated with rectal prolapse.
AB  - AIM: Solitary rectal ulcer syndrome (SRUS) is uncommon and its management is
      controversial. The aim of this study was to evaluate the outcome of patients with
      SRUS who underwent laparoscopic ventral rectopexy (LVR). METHOD: A review was
      performed of a prospective database at the Oxford Pelvic Floor Centre to identify
      patients between 2004 and 2012 with a histological diagnosis of SRUS. All were
      initially treated conservatively and surgical treatment was indicated only for
      patients with significant symptoms after failed conservative management. The
      primary end-point was healing of the ulcer. Secondary end-points included changes
      in the Wexner Constipation Score and Faecal Incontinence Severity Index (FISI).
      RESULTS: Thirty-six patients with SRUS were identified (31 women), with a median
      age of 44 (15-81) years. The commonest symptoms were rectal bleeding (75%) and
      obstructed defaecation (64%). The underlying anatomical diagnosis was internal
      rectal prolapse (n = 20), external rectal prolapse (n = 14) or anismus (n = 2).
      Twenty-nine patients underwent LVR and one a stapled transanal rectal resection
      (STARR) procedure. Nine (30%) required a further operation, six required
      posterior STARR for persistent SRUS and two a per-anal stricturoplasty for a
      narrowing at the healed SRUS site. Healing of the SRU was seen in 27 (90%) of the
      30 patients and was associated with significant improvements in Wexner and FISI
      scores at a 3-year follow-up. CONCLUSION: Almost all cases of SRUS in the present
      series were associated with rectal prolapse. LVR resulted in successful healing
      of the SRUS with good function in almost all patients, but a significant number
      will require further surgery such as STARR for persistent obstructed defaecation.

PMID- 24678527
TI  - The Sharpe Knife.

PMID- 24678528
TI  - A systematic comparative evaluation of 90Y-labeled bifunctional chelators for
      their use in targeted therapy.
AB  - This paper describes a systematic comparative evaluation of five commonly used
      bifunctional chelators, namely,p-isothiocyanato benzyl derivatives of
      diethylenetriaminepentacetic acid (DTPA-NCS), trans-cyclohexyl
      diethylenetriaminepentaceticacid (CHX-A"-DTPA-NCS), 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NCS), 1,4,7
      triazacyclononane-1,4,7-triacetic acid (NOTA-NCS), and 3,6,9,15-tetraazabicyclo
      [9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA-NCS), on the basis
      of their ability to complex 90Y at room temperature, in vitro and in vivo
      stability and clearance pattern in biological system. The results of the
      experiments carried out revealed that CHX-A"-DTPA-NCS was the most promising
      option as it could be radiolabeled with 90Y at room temperature with highest
      specific activity and demonstrated high in vitro stability in human serum and in
      presence of challenging metal ions commonly present inhuman plasma. The clearance
      pattern in Swiss mice revealed that 90Y-CHX- A"-DTPA-NCS cleared through the
      kidneys with minimum retention in any other major organ. Thus, the use of
      cyclohexyl-DTPA based bifunctional chelators would increase the scope of making
      90Y-labeled agents suitable for targeted therapy.

PMID- 24678529
TI  - "Welcome to the Machine".

PMID- 24678530
TI  - Treatment of metastatic melanoma with electrochemotherapy.
AB  - Superficially metastatic melanoma still represents a challenging situation for
      oncologists and a distressing condition for patients. In this circumstance, local
      treatment by electrochemotherapy, that is, the combination of brief
      permeabilizing electric pulses with a low-toxicity anticancer drug, can be a
      valuable treatment option in selected patients who are ineligible/refractory to
      systemic treatments or require rapid palliation of symptomatic cutaneous disease.

PMID- 24678531
TI  - Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a
      versatile building block in 18F radiochemistry.
AB  - 4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F
      radiochemistry used in various transition metal-mediated C-C and C-N cross
      coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes
      have been described for the preparation of [18F]FIB. However, to date, no
      automated synthesis of [18F]FIB has been reported to allow access to larger
      amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we
      describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlabTM
      FX automated synthesis unit starting from commercially available(4
      iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was
      prepared in high radiochemical yields of 89 +/- 10% (decay-corrected, n = 7)
      within 60 min, including HPLC purification. The radiochemical purity exceeded
      95%, and specific activity was greater than 40 GBq/MUmol. Typically, from an
      experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of
      [18F]fluoride.

PMID- 24678532
TI  - It is worth taking time to consider the scale and nature of falls among older
      people.

PMID- 24678533
TI  - Systems analysis of human multigene disorders. Preface.

PMID- 24678534
TI  - Research tools: Jump off the page.

PMID- 24678535
TI  - Alzheimer's disease and glaucoma-reply.

PMID- 24678536
TI  - Be here now.

PMID- 24678537
TI  - Wheat lag.

PMID- 24678538
TI  - A parlous state.

PMID- 24678539
TI  - Physics: QBism puts the scientist back into science.

PMID- 24678540
TI  - Preclinical research: Make mouse studies work.

PMID- 24678541
TI  - Response to Sheehan, Brorby, Berman, and Bogen, 'protecting good science.'.

PMID- 24678542
TI  - [Huntington's disease].

PMID- 24678543
TI  - [Inflammation and depression: the role of oxidative stress, hormonal and cellular
      factors].

PMID- 24678544
TI  - Visual vignette.

PMID- 24678545
TI  - 'Not just methadone Tracy': transformations in service-user identity following
      the introduction of hepatitis C treatment into Australian opiate substitution
      settings.
AB  - AIMS: To explore identity transformation among service users attending opiate
      substitution therapy (OST) clinics following the introduction of hepatitis C
      (HCV) care and treatment. DESIGN: An interview-based substudy of the Australian
      ETHOS (Enhancing Treatment for Hepatitis C in Opiate Substitution Settings)
      project. SETTING: Three OST clinics and one community health centre (operating a
      public OST) in New South Wales, Australia. Participants were interviewed at the
      recruitment sites. PARTICIPANTS: The sample consisted of 57 OST service users
      concurrently living with HCV, 16 staff, including specialist HCV clinicians, and
      three peer-support workers, employed on the ETHOS project. MEASUREMENTS: Semi
      structured interviews. FINDINGS: Service-user participants largely welcomed the
      introduction of HCV treatment as a practical, clinical intervention that also
      intimated a more comprehensive, holistic form of care. Negative stereotypes
      characteristic of OST settings-of limited, routinized clinical exchanges and
      minimal social-care interaction-were unsettled, opening up the possibility of new
      relations between staff and service users. The shift in the dynamic of the
      clinical encounter to address health in addition to dependence appeared to
      catalyse transformative possibilities not only for the therapeutic alliance but
      also for service-user understandings of self and identity. CONCLUSION: Trial
      introduction of HCV care and treatment in selected Australian opiate substitution
      therapy (OST) clinics may have facilitated alternative, 'non-addict' identities
      to emerge from a clinical setting where the stigmatizing figure of 'the drug
      user' has traditionally prevailed.

PMID- 24678546
TI  - Bone marrow aspirate showing Histoplasma capsulatum.

PMID- 24678547
TI  - A hairy issue.

PMID- 24678548
TI  - [Limited resources: a challenge ahead].

PMID- 24678550
TI  - Volunteering in Nepal to make a difference.

PMID- 24678549
TI  - iPhones for nurses.

PMID- 24678551
TI  - Educating young Aussie men is key to reducing prostate cancer toll.

PMID- 24678552
TI  - Dads' guide to pregnancy.

PMID- 24678553
TI  - End of an era: tribute to Australian POW nurse.

PMID- 24678554
TI  - Professions rally against changes to Medicare.

PMID- 24678555
TI  - More than just menopause.

PMID- 24678556
TI  - Smokers in denial over health effects.

PMID- 24678557
TI  - Cancer nurse first to benefit from treatment.

PMID- 24678558
TI  - Women may need different blood pressure treatment.

PMID- 24678559
TI  - Ovarian cancer awareness.

PMID- 24678560
TI  - Midwifery services slashed in Queensland.

PMID- 24678561
TI  - Different cultures deliver different births.

PMID- 24678562
TI  - Influence of the workplace on learning physical examination skills.
AB  - BACKGROUND: Hospital clerkships are considered crucial for acquiring competencies
      such as diagnostic reasoning and clinical skills. The actual learning process in
      the hospital remains poorly understood. This study investigates how students
      learn clinical skills in workplaces and factors affecting this. METHODS: Six
      focus group sessions with 32 students in Internal Medicine rotation (4-9 students
      per group; sessions 80-90 minutes). Verbatim transcripts were analysed by
      emerging themes and coded independently by three researchers followed by constant
      comparison and axial coding. RESULTS: Students report to learn the systematics of
      the physical examination, gain agility and become able to recognise pathological
      signs. The learning process combines working alongside others and working
      independently with increasing responsibility for patient care. Helpful behaviour
      includes making findings explicit through patient files or during observation,
      feedback by abnormal findings and taking initiative. Factors affecting the
      process negatively include lack of supervision, uncertainty about tasks and
      expectations, and social context such as hierarchy of learners and perceived
      learning environment. CONCLUSION: Although individual student experiences vary
      greatly between different hospitals, it seems that proactivity and participation
      are central drivers for learning. These results can improve the quality of
      existing programmes and help design new ways to learn physical examination
      skills.

PMID- 24678563
TI  - Effect of covalent fluorescence labeling of plasmid DNA on its intracellular
      processing and transfection with lipid-based carriers.
AB  - The development of biotechnological pharmaceutics, like macro- and nanocarriers,
      can benefit greatly from studying their characteristics in situ using advanced
      fluorescence microscopy methods. While choosing the optimal labeling method for
      visualizing the carrier or its cargo is crucial, it seldom receives attention.
      The possibility that high labeling densities alter the intracellular processing
      of the molecule is considered, but how and at which point this interference
      happens is not yet studied. The aim of this study was to elucidate the effect of
      labeling density on the cellular trafficking of labeled pDNA. Due to the drastic
      effect on expression levels for higher labeling densities, we tried to determine
      at which steps in the intracellular processing labeled pDNA behaves different
      than its nonlabeled counterpart. Therefore, different labeling densities, up to
      the manufacturer's recommended density, were tested. It was found that the
      cellular uptake remains unaffected, while the affinity for lipids is increased,
      which affects dissociation from the lipid-based complex and may affect endosomal
      escape. Also, nuclear injections clearly demonstrated that transcription is
      affected. The information and methodology, included in this work, could be
      helpful in determining if the labeling method and density used yields biological
      relevant results for the intended research question. 

PMID- 24678564
TI  - Driving during alcohol hangover among dutch professional truck drivers.
AB  - OBJECTIVES: Alcohol hangover may impair potentially dangerous daily activities
      such as driving a car or operating heavy machinery. The purpose of the present
      study was to determine (1) whether driving during alcohol hangover is a problem
      of concern among professional Dutch truck drivers and (2) to what extent they
      think their hangover state affects driving performance. METHODS: Three hundred
      forty-three professional truck drivers were interviewed at a Dutch trucker
      festival. In addition to demographics, data were gathered on normal driving,
      alcohol consumption and hangover, and driving style during alcohol hangover.
      RESULTS: More than half of the professional drivers who consume alcohol and
      report occasionally having a hangover (56.4%) acknowledge that they have driven
      while having a hangover during the past year: 26.5 percent only when driving
      private, 2.6 percent only when driving professionally, and 27.4 percent both
      private and professionally. Additionally, 45.3 percent reported driving while
      having a hangover sometimes, whereas 7.7 percent and 1.7 percent reported doing
      so often or always, respectively. During alcohol hangover, professional drivers
      rated their driving style as significantly less relaxed, less safe, and less
      responsible (P < .001). CONCLUSIONS: Driving with a hangover is a common
      phenomenon, and professional drivers acknowledge that their driving is impaired.
      Therefore, future experimental research should examine the magnitude of
      impairment while driving with an alcohol hangover.

PMID- 24678565
TI  - Meta-analysis of on-the-road experimental studies of hypnotics: effects of time
      after intake, dose, and half-life.
AB  - BACKGROUND: The use of hypnotics is prevalent in the general population. Though
      these drugs have been shown to be effective, their residual effects may cause
      significant impairment to the user's driving ability. The objective of this meta
      analysis is to determine whether there is a residual effect on driving and better
      evaluate the safety of hypnotics. METHOD: Randomized double-blind placebo
      controlled studies were selected that employed a commonly used and valid driving
      measure to determine the user's driving ability the day after drug
      administration. The primary outcome measure for the driving task in all included
      studies was the Standard Deviation of Lateral Position (SDLP). Fixed effects
      model meta-analyses were performed. RESULTS: Fourteen studies, published from
      1984 to 2013 (295 subjects), were included in this meta-analysis. Overall,
      significant impairment was found when morning testing (i.e., 10-11 h after
      initiating sleep) was compared to afternoon testing (i.e., 16-17 h after
      initiating sleep; P = .0001). Twice the standard dose also showed significant
      impairment (P = .0001) relative to the standard dose. The time of the test,
      morning versus afternoon, also had an impact on individual drugs. Middle of the
      night administration (MOTN) of zolpidem and zopiclone caused significant
      impairment the following morning, though no such impairment was seen with
      zaleplon. Finally, half-life was also assessed (short: <6 h, intermediate: 6-12
      h, long: >12 h) and both intermediate- and long-acting drugs caused significant
      impairment the morning after bedtime administration, whereas short acting
      hypnotics did not. CONCLUSIONS: These analyses indicate that the half-life, dose
      of the hypnotic, as well as time between treatment and driving, as measured by
      SDLP, all significantly impact the ability to drive a car after taking hypnotic
      drugs.

PMID- 24678567
TI  - Effect of passenger presence on older drivers' risk of fatal crash involvement.
AB  - OBJECTIVE: To determine the association between passenger presence and risk of
      fatal crash involvement in relation to driver and passenger age and gender,
      focusing especially on drivers ages 65 and older. METHODS: Data on US fatal
      crashes were obtained for 2002-2009. Using the quasi-induced exposure
      methodology, logistic regression analysis was used to predict the odds of fatal
      crash involvement as a function of driver age and gender as well as passenger age
      and gender. RESULTS: Overall, risk of fatal crash involvement with passengers was
      43 percent lower for drivers ages 65-74 and 38 percent lower for drivers 75 and
      older. Older drivers' risk of fatal crash involvement was lower with almost all
      combinations of passenger age and gender; there was no reduction in risk with
      passengers ages 75 and older. Effects were stronger at nonintersection locations
      than at intersection locations. CONCLUSION: Older drivers' crash risk is lower
      with almost every combination of passenger age group and gender. It is unclear
      whether the presence of passengers lowers older driver crash risk or whether
      safer drivers tend to ride with passengers.

PMID- 24678566
TI  - Compliance with traffic laws by traffic police officers, non-traffic police
      officers, and civilian drivers.
AB  - OBJECTIVE: The policy of a public organization, such as police, may shape the
      norms and the behavior of the citizens. In line with this, police officers are
      expected by the public to comply with traffic laws and serve as an example for
      the citizenry. This study used on-site observations of civilian and police
      driver, comparing police officers' compliance with traffic laws to that of
      civilians. METHODS: We compared driver compliance with traffic laws for drivers
      in 3 groups of vehicles: traffic police cars, non-traffic police cars, and
      civilian cars. Four hundred sixty-six vehicles were observed and compared by
      vehicle type and whether a uniform was worn by the driver. We observed safety
      belt usage, signaling before turning, cellular phone usage, and giving way to
      traffic (measured by merging time). RESULTS: We found evidence that generally
      drivers in police cars use seat belts while driving more that drivers in civilian
      cars do. In particular, more traffic police car drivers used seat belts than non
      traffic police car drivers do. In addition, drivers in civilian cars and non
      traffic police cars waited longer periods of time before merging right into
      traffic compared to traffic police car drivers. CONCLUSIONS: Our findings
      supported the notion that on-duty police officers, and traffic police officers in
      particular, adhere more closely to traffic laws compared to civilian drivers. As
      the general public compliance with traffic laws is affected by the police
      perceived legitimacy, the publication of these results can both boost public
      cooperation with the police and encourage police officers to continue providing
      positive role models to the public.

PMID- 24678568
TI  - Light-vehicle occupancy and severe injury by vehicle and crash type.
AB  - PURPOSE: This study investigated the number of occupants involved and severely
      injured in light-vehicle crashes by vehicle and crash type. METHODS: 1994-2010
      NASS-CDS data were analyzed to estimate the risk of severely injured occupants
      involved in motor vehicle crashes. Crashes were grouped by front, side, rear, and
      rollovers. The effect of occupancy and vehicle type was investigated. Light
      vehicles were less than 4536 kg with model year 1994+. The annual number of
      Maximum Abbreviated Injury Scale (MAIS) 4+F injuries was estimated and the risk
      was determined using all occupants with known injury (MAIS 0-6+F). RESULTS: There
      were 21,869 MAIS 4+F injuries annually, with 62.7 percent involving passenger
      cars, 15.9 percent sport utility vehicles (SUVs), 15.3 percent trucks, and 6.1
      percent vans. In 36.6 percent of van crashes, MAIS 4+F occurred when there were
      4+ occupants and 13.0 percent with 7+ occupants in the vehicle. Overall, 12.8
      percent of severely injured were in crashes involving 4+ occupants and 1.4
      percent with 7+ occupants. In addition, 30.1 percent of MAIS 4+F occurred in
      rollovers and only 5.8 percent of crashes were rollovers. Rollovers had the
      highest injury risks, irrespective of the number of occupants. There was a trend
      for an increased fraction of injury in frontal crashes and a lower fraction in
      rollovers. There were high risks in side and rear crashes with 5+ occupants.
      CONCLUSIONS: On average, there were 1.35 occupants involved in a crash per
      vehicle. Severely injured occupants were uncommon in 5+ occupancy vehicles. There
      was a trend for increased injury risks with occupancy. The risk was 1.65 times
      higher in vehicles with 7+ occupants compared to those with a driver only.

PMID- 24678569
TI  - The scope and nature of injuries to rear seat passengers in NSW using linked
      hospital admission and police data.
AB  - OBJECTIVE: To compare the pattern of injuries to front and rear seat occupants
      and test the hypothesis that rear seat passengers of different ages sustain
      different patterns of injury. METHOD: Patients admitted to a hospital following
      involvement in a crash in New South Wales (NSW) Australia between 2005 and 2007
      were identified using International Classification of Diseases (10th edition
      [ICD10]) codes. Hospital admissions data were linked with NSW police crash data
      using probabilistic techniques. The profiles and patterns of injury of front and
      rear seat passengers were compared. Logistic regression was used to examine how
      age influenced the pattern of injury among rear seat passengers. RESULTS: Sixty
      three percent of hospital admissions were linked with police records. One in 5
      passengers were rear seat passengers. There were more unrestrained occupants in
      the rear (7%) compared to drivers (3%) and front seat passengers (2%). Younger (9
      15 years) injured passengers were seated in the rear more often than in the front
      passenger position and older injured passengers (>50 years) were seated more
      often in the front passenger position than in the rear (15% rear compared to 5%
      front aged 9-15 years; 22% rear compared to 37% front aged >50 years; chi(2), P <
      .001). There were proportionally more fatal injuries among rear seat passengers
      (10%) than among drivers (5%) and front seat passengers (6%), and the pattern of
      injury between front and rear passengers also varied. Rear seat passengers had
      more head and abdominal injuries and fewer thoracic and knee/lower leg injuries
      than front seat passengers. After adjusting for vehicle age, restraint status,
      travel speed, and whether or not a fatality occurred in the crash, older (>50
      years) rear passengers had 6.3 times the odds of sustaining thoracic injuries
      (95% confidence interval [CI], 2.6-15.0) and lower odds (odds ratio [OR] = 0.4,
      95% CI, 0.2-0.9) of sustaining abdominal/lumbar injuries than the youngest
      occupants (9-15 years).The odds of sustaining a head injury did not vary with
      age, and the odds of sustaining thoracic, abdominal, or lower extremity injuries
      did not differ significantly between rear seat passengers aged 16-50 years and 9
      15 years. CONCLUSIONS: The findings suggest that there is a need for enhanced
      protection for rear seat passengers, because they have proportionally more fatal
      injuries than front-seated occupants. The frequency of abdominal injury and the
      differences between injury patterns observed in front seat passengers suggests a
      potential benefit from adding abdominal injury risk assessment to rear seat
      occupant protection test protocols. There is also scope to improve chest
      protection for older rear seat passengers.

PMID- 24678570
TI  - Elevated risk of sleepiness-related motor vehicle accidents in patients with
      obstructive sleep apnea syndrome: a case-control study.
AB  - OBJECTIVES: The present case-control study aimed to determine whether obstructive
      sleep apnea syndrome (OSAS) patients are at an increased risk for sleepiness
      related motor vehicle accidents (MVAs) than controls and to identify disease
      related factors associated with accident risk. METHODS: Demographic,
      anthropometric, clinical, and polysomnographic parameters of 312 OSAS patients
      were compared with 156 age- and sex-matched primary snoring subjects. RESULTS:
      The rate of OSAS patients reporting accident was higher than snoring subjects
      (21.2% vs. 11.5%, P = .011), and OSAS was associated with an increase in accident
      risk (odds ratio = 2.06, 95% confidence interval [CI], 1.17 to 3.61, P = .012).
      Younger OSAS patients (P = .001) and those who were male (P = .001), had greater
      neck circumference (P = .002), had a higher Epworth sleepiness score (ESS; P <
      .0001), and had a higher apnea-hypopnea index (AHI; p = .039) had more MVAs than
      OSAS patients. Daytime sleepiness was associated with a 2.74-fold increase (95%
      CI, 1.54 to 4.87, P = .001) in accident risk. In multiple logistic regression
      analysis, accident risk was associated with neck circumference (P < .031) and ESS
      (P < .0001). In addition, accident risk could be excluded in OSAS patients with
      neck circumference < 43 cm and ESS < 11 (sensitivity 33.3%, specificity 85.8%).
      CONCLUSIONS: The present results show that OSAS patients have a twofold higher
      risk of traffic accidents than control subjects, and increased neck circumference
      and excessive daytime sleepiness are useful in predicting OSAS patients at higher
      risk of having accidents.

PMID- 24678571
TI  - Buckle up safely (shoalhaven): a process and impact evaluation of a pragmatic,
      multifaceted preschool-based pilot program to increase correct use of age
      appropriate child restraints.
AB  - OBJECTIVE: To conduct a process and impact evaluation of a multifaceted education
      based pilot program targeting correct use of age-appropriate restraints in a
      regional setting with a high proportion of Aboriginal and Torres Strait Islander
      families. METHODS: The program was delivered in 2010 in 3 early learning centers
      where 31 percent of the children were of Aboriginal and Torres Strait Islander
      descent. Each component of the program was assessed for message consistency and
      uptake. To measure program effectiveness, participating children were matched 1:1
      by age, language spoken at home, and annual household income with 71 children
      from the control arm of a contemporaneous trial. The outcome measure in the
      control and program centers (a 4-category ordinal scale of restraint use) was
      compared using ordinal logistic regression accounting for age of the parent.
      RESULTS: Process evaluation found that though program components were delivered
      with a consistency of message, uptake was affected by turnover of all staff at
      one center and by parents experiencing difficulty in paying for subsidized
      restraints at each of the centers. Impact evaluation found that children from the
      centers receiving the program had nearly twice the odds of being in a better
      restraint category than children matched from the control group (adjusted odds
      ratio [ORadj] = 2.06, 95% confidence interval [CI], 1.09-3.90). CONCLUSIONS: This
      was a pragmatic study reflecting the real-life issues of implementing a program
      in preschools where 57 percent of families had a low income and turnover of staff
      was high. Despite these issues, impact evaluation showed that the integrated
      educational program showed promise in increasing correct use of age-appropriate
      restraints. The findings from this pilot study support the use of an integrated
      educational program that includes access to subsidized restraints to promote best
      practice child restraint use among communities that include a high proportion of
      Aboriginal and Torres Strait Islander families in New South Wales. Future trials
      in similar settings should consider offering more support in centers with high
      turnover of staff and offering alternative methods of payment when families
      experience financial difficulties in purchasing the subsidized restraints. If
      proven in larger trials, this approach could reduce death and injuries in child
      passengers in this vulnerable group.

PMID- 24678572
TI  - The use of self-report exposure measures among novice motorcyclists:
      appropriateness and best practice recommendations.
AB  - OBJECTIVES: While self-report methods to collect exposure information have large
      practical advantages in many research contexts, little research has specifically
      investigated the reliability and validity of motorcyclists' self-reported
      exposure. The present study aimed to examine the reliability and validity of
      different self-report exposure measures and to provide recommendations on best
      practice self-report riding exposure questions. METHODS: The reliability and
      validity of different self-report exposure measures were examined amongst novice
      motorcyclists through t-tests, Bland Altman plots, coefficients of variation, and
      correlations. RESULTS: The most valid and reliable data was provided when riding
      exposure was asked for the current average week rather than earlier and longer
      periods, and in units of time rather than distance or number of trips. The
      greater reliability of riding exposure found amongst commuting and rural riders
      compared to recreational and metropolitan riders respectively and at the second
      interview compared to the first suggests that factors such as riding purposes,
      geographical locations, and riding experience can contribute to measurement
      error. CONCLUSIONS: If self-reported odometer readings are used, questions on
      whether the respondents share their own bike or ride more than one bike, and a
      built-in process to ensure respondents report the exact odometer reading on their
      bike are recommended. It is recommended that self-report riding exposure
      questions ask about the hours of riding for the current average week, and data on
      riding purposes, locations, and experience are also collected.

PMID- 24678573
TI  - Distribution and type of crash damage to motorcyclists' clothing: validation of
      the zone approach in the European Standard for motorcycle protective clothing,
      EN13595.
AB  - OBJECTIVE: Though the use of protective clothing reduces the risk of injury for
      motorcycle riders, not all protective clothing performs the same in crashes. A
      European Standard for motorcycle protective clothing (EN13595) was released in
      2002 that specifies 4 zones in motorcycle clothing with different levels of
      protective qualities and 4 different test methods for assessing damage
      resistance. This project examined damage location and type in clothing worn by
      riders following a crash to establish the distribution of impact points and
      validate the zones described in EN13595. METHOD: Data from 117 crashed motorcycle
      riders collected during crash investigation were examined. These data included
      medical data and clothing inspections and contained 576 cases of clothing damage.
      To ensure that the impact point distribution included all possible contact
      locations, an additional 433 distinct injury locations were examined where injury
      had occurred but clothing was either undamaged or not present at that location.
      Descriptive techniques were used in the analysis. RESULTS: The majority of damage
      occurred in areas covering the extremities or pelvic girdle (93%), with most
      occurring on the wrists and hands (18%) and ankles and feet (18%). Clothing
      regions covering the shoulder (10%), forearm (10%), elbow (9%), thigh (7%), lower
      leg (6%), and pelvic-hip region (5%) were also frequently damaged. Other body
      regions contributed only 8 percent of damage seen. Analysis of distinct injury
      locations demonstrated a similar distribution of impact. The most common types of
      clothing damage were abrasion, accounting for 69 percent, and torn material,
      which accounted for 26 percent of all damage. Further, the majority of material
      abrasion and tearing occurred in regions corresponding to zone 1, followed by
      zones 2, 3, and then 4. There were very few instances (3%) of burst and cut
      damage. CONCLUSIONS: The results are in agreement with the general concept of the
      zones used in the EU Standard. However, these results indicate that minor
      adjustments may be warranted. In particular, the number of impacts to the forearm
      and lower leg suggest that these regions might be better protected by considering
      the whole regions as zone 1or 2 rather than the multiple regions as currently
      indicated in the EU Standard. However, the subjective nature of determining the
      zone in which damage (and/or injury) occurred limits these findings and any
      others that attempt to validate the zone principles using real-world data.
      Further validation requires consideration of the severity of impact at different
      zones.

PMID- 24678574
TI  - Involvement of unendorsed motorcycle operators in fatal crashes in Cuyahoga
      County, Ohio, 2005-2011.
AB  - OBJECTIVE: This study examines the role of unendorsed motorcycle operators in
      fatal motorcycle crashes and the interrelationships of endorsement status and
      motorcycle type with operator characteristics like riding impaired. METHODS:
      Cases were drawn from a database tracking fatal crashes occurring within Cuyahoga
      County, Ohio, from 2005 to 2011. Analysis focused on 75 fatal motorcycle crashes
      in which the deceased motorcycle operators were male and coroner's reports,
      police crash reports, and license endorsement status were available. Analysis
      included comparison of means, chi square testing, and binary logistic regression.
      RESULTS: More than half of motorcyclists (53%) did not have motorcycle
      endorsements. Mean age of unendorsed riders was 36.8 years, compared to 44.2
      years for endorsed riders. Motorcyclists were considered at fault in 69 percent
      of cases, most often due to reckless operation, failure to control, or speeding.
      Mean blood alcohol concentration for fatally injured motorcyclists was 0.06
      percent. Marijuana was the most common drug identified in blood tests.
      Nonendorsement was associated with younger age, single-vehicle crash, and having
      a prior license suspension. Neither endorsement status nor bike type was
      associated with likelihood of testing positive for alcohol or drugs of abuse.
      Riders of sport motorcycles were more likely than cruiser/touring bike operators
      to be wearing helmets and less likely to be endorsed. CONCLUSION: The large
      proportion of unendorsed motorcyclists involved in fatal crashes in northeast
      Ohio highlights the need for more stringent licensing requirements that make it
      more difficult to ride without an endorsement and limit learner's permit
      renewals.

PMID- 24678575
TI  - A numerical investigation on the variation in hip injury tolerance with occupant
      posture during frontal collisions.
AB  - OBJECTIVE: More than half of occupant lower extremity (LEX) injuries during
      automotive frontal crashes are in the knee-thigh-hip (KTH) complex. The objective
      of this study is to develop a detailed and biofidelic finite element (FE)
      occupant LEX model that may improve current understanding of mechanisms and
      thresholds of KTH injuries. METHODS: Firstly, the pelvis, thigh-knee-hip, and
      foot models developed in our previous studies were connected into an occupant
      lower limb model. Further validations, including posterior cruciate ligament
      (PCL) stretching, thigh lateral loading, KT, and KTH impact loading were then
      performed to verify the injury predictability of the model under complex frontal
      and lateral loading corresponding to automotive impacts. Finally, a sensitivity
      study was performed with the whole lower limb model to investigate the effect of
      the hip joint angle to acetabulum injury tolerance in frontal impacts. RESULTS:
      The whole lower limb model proved to be stable under severe impacts along the
      knee, foot, and lateral components. In addition, the biomechanical and injury
      responses predicted by the model correlated well with the corresponding test
      data. An increase in hip joint extension angle from -30 to +20 degrees  relative
      to neutral posture showed an increase of 19 to 58 percent hip injury tolerance.
      CONCLUSIONS: The stability and biofidelity response of the pelvis-lower limb
      (PLEX) model indicates its potential application in future frontal and lateral
      impact FE simulations.

PMID- 24678576
TI  - Effects of translational and vibrational excitation on the reaction of HOD+ with
      C2H2 and C2D2: mode- and bond-specific effects in exoergic proton transfer.
AB  - Reactions of mode-selectively excited HOD(+) with C2H2 and C2D2 were studied over
      the center-of-mass collision energy (Ecol) range from 0.15 to 2.9 eV. HOD(+) was
      prepared in each of its fundamental vibrational states: ground state (000), bend
      (010), OD stretch (100), and the OH stretch (001). Charge transfer is the
      dominant reaction at all energies, although it is inhibited by increasing Ecol,
      and is accompanied by hydrogen exchange. The total charge transfer cross section
      is similar for C2H2 and C2D2, however, the tendency toward charge transfer with
      hydrogen exchange (CTHE) is significantly greater for C2D2 compared to C2H2.
      Charge transfer shows no significant effects of HOD(+) vibrational excitation,
      however, CTHE is significantly enhanced by vibration at Ecol < 0.62 eV. Both H(+)
      and D(+) transfer reactions (HT, and DT, respectively) are observed for both C2H2
      and C2D2, with little dependence on collision energy, but with mode- and bond
      specific enhancements from excitation of the OH and OD stretches. Recoil velocity
      measurements show that all channels are direct, except perhaps at the lowest
      collision energies. Mode-specific effects on the recoil velocity distributions
      are also observed, revealing how vibrational excitation affects reaction at
      different collision impact parameters. 

PMID- 24678577
TI  - Mean platelet volume: A novel prognostic factor of rotavirus gastroenteritis?

PMID- 24678578
TI  - Adolescent obesity, joint pain, and hypermobility.
AB  - BACKGROUND: Obesity associated with joint pain of the lower extremities is likely
      due to excessive mechanical load on weight bearing joints. Additional mechanical
      factors may explain the association between obesity and joint pain. FINDINGS: We
      characterized the association between obesity and non-traumatic lower extremity
      (LE) joint pain in adolescents and examined the modifying effect of hypermobility
      on this association.We performed a cross-sectional analysis of data from subjects
      enrolled in a clinical trial examining the impact of weight loss on bone health
      in adolescents. Anthropometric data were collected and body mass index (BMI =
      kg/m2) was calculated. Subjects were categorized as obese or healthy weight
      controls based on CDC 2000 growth curves for age and gender. We assessed any
      musculoskeletal pain and LE pain by the PEDSTM Pediatric Pain QuestionnaireTM.
      Hypermobility was assessed with the modified Beighton scoring system.
      Multivariate logistic regression models adjusted for covariates were performed to
      examine the association between weight status and joint pain.Out of 142 subjects,
      91 were obese and 51 were healthy weight. Obesity was not associated with any
      musculoskeletal pain (OR 0.86, CI 0.49-1.50), LE pain (OR 1.02, CI 0.49-2.15) or
      hypermobility (OR 1.23, CI 0.72-2.14, p = 0.3). There was no effect modification
      on the association between obesity and any musculoskeletal pain (OR 0.80, CI 0.45
      -1.42) or LE pain (OR 0.98, CI 0.46 - 2.08) by hypermobility status. CONCLUSIONS:
      We found no association between LE pain and obesity, and hypermobility did not
      modify this association.

PMID- 24678579
TI  - Selecting an interprofessional education model for a tertiary health care
      setting.
AB  - The World Health Organization describes interprofessional education (IPE) and
      collaboration as necessary components of all health professionals' education - in
      curriculum and in practice. However, no standard framework exists to guide
      healthcare settings in developing or selecting an IPE model that meets the
      learning needs of licensed practitioners in practice and that suits the unique
      needs of their setting. Initially, a broad review of the grey literature
      (organizational websites, government documents and published books) and
      healthcare databases was undertaken for existing IPE models. Subsequently,
      database searches of published papers using Scopus, Scholars Portal and Medline
      was undertaken. Through this search process five IPE models were identified in
      the literature. This paper attempts to: briefly outline the five different models
      of IPE that are presently offered in the literature; and illustrate how a
      healthcare setting can select the IPE model within their context using Reeves'
      seven key trends in developing IPE. In presenting these results, the paper
      contributes to the interprofessional literature by offering an overview of
      possible IPE models that can be used to inform the implementation or modification
      of interprofessional practices in a tertiary healthcare setting.

PMID- 24678580
TI  - A proposed interprofessional oath.
AB  - Identifying and capitalizing on shared professional values, health-care
      professionals have the potential to promote collaboration and facilitate enhanced
      patient outcomes. This paper describes a qualitative study that sought to
      identify values shared among health-care professionals through the development of
      an interprofessional health-care provider oath. Core competencies for
      collaborative practice of all health-care workers were delineated by the recent
      report from the Interprofessional Education Collaborative Expert Panel and these
      include values and ethics of collaboration as well as an understanding of team
      roles. This proposed interprofessional oath was developed from a qualitative
      analysis of oaths developed by interprofessional teams of health-care students.
      Using Colaizzi's method, 18 oaths were evaluated to identify significant
      statements, formulated meanings, and themes. A proposed interprofessional oath
      was developed based on these elements and is offered for consideration along with
      discussion of the potential benefits and challenges of an interprofessional oath.

PMID- 24678581
TI  - Postnatal nutritional iron deficiency impairs dopaminergic-mediated synaptic
      plasticity in the CA1 area of the hippocampus.
AB  - OBJECTIVES: Developmental iron deficiency (ID) has been shown to put children at
      risk for compromised learning and memory capacity, and it has also been shown to
      impair hippocampus-dependent forms of memory as well as hippocampal synaptic
      transmission. Catecholamines are known to play a pivotal role in memory
      consolidation, and studies have demonstrated that perinatal ID alters
      dopaminergic systems in various brain areas. It is not known, however, whether
      perinatal ID impairs dopaminergic synaptic plasticity in learning and memory
      structures such as the hippocampus. The objective of the present study was to
      examine dopaminergic-mediated synaptic efficacy in the hippocampus of mice
      subjected to an ID or control (CN) diet. METHODS: The present study used
      electrophysiological brain slice methods to examine dopaminergic-mediated
      synaptic efficacy in the hippocampus of mice subjected to an ID or CN diet from
      postnatal day (P) P0 through P20. Hippocampal brain slices were prepared in young
      (P26-30) and adult animals (P60-64). Synaptic efficacy was measured in CA1
      neurons by examining population spike amplitude. Slices were treated with the
      dopaminergic agonist SKF-38393. RESULTS: Slices obtained from young and adult CN
      mice exhibited a long-lasting increase in synaptic efficacy as the result of SKF
      38393 perfusion while the young and adult ID slices showed little or no increase.
      DISCUSSION: The present study demonstrates that postnatal ID produces long
      lasting impairments in dopaminergic-dependent synaptic plasticity in the
      hippocampus. These impairments may play a role in the learning and memory
      deficits known to result from ID.

PMID- 24678582
TI  - Reversal of reduced parvalbumin neurons in hippocampus and amygdala of Angelman
      syndrome model mice by chronic treatment of fluoxetine.
AB  - Angelman syndrome (AS) is a neuropsychiatric disorder characterized by autism,
      intellectual disability and motor disturbances. The disease is primarily caused
      by the loss of function of maternally inherited UBE3A. Ube3a maternal-deficient
      mice recapitulates many essential feature of AS. These AS mice have been shown to
      be under chronic stress and exhibits anxiety-like behaviour because of defective
      glucocorticoid receptor signalling. Here, we demonstrate that chronic stress in
      these mice could lead to down-regulation of parvalbumin-positive interneurons in
      the hippocampus and basolateral amygdala from early post-natal days. Down
      regulation of parvalbumin-positive interneurons number could be because of
      decrease in the expression of parvalbumin in these neurons. We also find that
      treatment with fluoxetine, a selective serotonin reuptake inhibitor, results in
      restoration of impaired glucocorticoid signalling, elevated serum corticosterone
      level, parvalbumin-positive interneurons and anxiety-like behaviours. Our
      findings suggest that impaired glucocorticod signalling in hippocampus and
      amygdala of AS mice is critical for the decrease in parvalbumin interneurons
      number, emergence of anxiety and other behavioural deficits and highlights the
      importance of fluoxetine in the recovery of these abnormalities.

PMID- 24678584
TI  - Production, purification, and antibiofilm activity of a novel exopolysaccharide
      from Arthrobacter sp. B4.
AB  - A novel exopolysaccharide (EPS), namely, B4-EPS, is produced by Arthrobacter sp.
      B4. Response surface methodology (RSM) was employed to optimize the fermentation
      medium for increasing B4-EPS production. Based on Plackett-Burman design (PBD),
      glucose, yeast extract, and KH2PO4 were selected as significant variables, which
      were further optimized by a central composite design (CCD). According to response
      surface and canonical analysis, the optimal medium was composed of 16.94 g/L
      glucose, 2.33 g/L yeast extract, and 5.32 g/L KH2PO4. Under this condition, the
      maximum yield of B4-EPS reached about 8.54 g/L after 72 hr of batch fermentation,
      which was pretty close to the predicted value (8.52 g/L). Furthermore, B4-EPS was
      refined by column chromatography. The main homogeneous fraction (B4-EPS1) was
      collected and applied to assay of antibiofilm activity. B4-EPS1 exhibited a dose
      dependent inhibitory effect on biofilm formation of Pseudomonas aeruginosa PAO1
      without antibacterial activity. About 86.1% of biofilm formation of P. aeruginosa
      PAO1 was inhibited in the presence of 50 ug/mL B4-EPS1, which was more effective
      than the peer published data. Moreover, B4-EPS1 could prevent biofilm formation
      of other strains. These data suggest B4-EPS may represent a promising strategy to
      combat bacterial biofilms in the future. 

PMID- 24678585
TI  - Patient experience with a novel patch-like external loop recorder for cardiac
      arrhythmia detection in India.
AB  - Cardiovascular disease (CVD) is reaching pandemic proportions in India. The
      effects of CVD are disastrous for the Indian economy as the disease strikes in
      the prime working ages of the labor force. The great need for therapeutic and
      diagnostic options combined with pressure on cost containment place emphasis on
      the development of low cost, credible, point of care diagnostic tools to pinpoint
      issues in cardiac health for the Indian consumer. A previous study of 125
      patients in India examined a novel external loop recorder (ELR) for ambulatory
      ECG monitoring with high yield and compliance. The current study probes the
      patient experience, inclusive of patient comfort, ease of use, clarity of the
      diagnostic report, and value of the ELR. The analysis shows that 85% found this
      ELR comfortable to wear and deploy, 77% responded with no challenges with the use
      of this ELR, 60% mentioned they were inclined to seek treatment after this ELR
      was deployed, and 60% found good value in the device. The results indicate that
      this particular ELR is a high performing device with excellent patient
      satisfaction, indicating that the device is a suitable tool for diagnosis of
      cardiac arrhythmia in India.

PMID- 24678583
TI  - Associations between inadequate sleep and obesity in the US adult population:
      analysis of the national health interview survey (1977-2009).
AB  - BACKGROUND: Epidemiologic studies show a curvilinear relationship between
      inadequate sleep (< 7 or > 8 hours) and obesity (Body Mass Index > 30 kg/m2),
      which have enormous public health impact. METHODS: Using data from the National
      Health Interview Survey, an ongoing nationally representative cross-sectional
      study of non-institutionalized US adults (>=18 years) (1977 through 2009), we
      examined the hypothesis that inadequate sleep is independently related to
      overweight/obesity, with adjustment for socio-demographic, health risk, and
      medical factors. Self- reported data on health risks, physician-diagnosed medical
      conditions, sleep duration, and body weight and height were used. RESULTS:
      Prevalence of overweight and obesity increased from 31.2% to 36.9% and 10.2% to
      27.7%, respectively. Whereas prevalence of very short sleep (<5 hours) and short
      sleep (5-6 hours) has increased from 1.7% to 2.4% and from 19.7% to 26.7%, it
      decreased from 11.6% to 7.8% for long sleep. According to multivariate-adjusted
      multinomial regression analyses, odds of overweight and obesity associated with
      very short sleep and short sleep increased significantly from 1977 to 2009. Odds
      of overweight and obesity conferred by long sleep did not show consistent and
      significant increases over the years. Analyses based on aggregated data showed
      very short sleepers had 30% greater odds of being overweight or were twice as
      likely to be obese, relative to 7-8 hour sleepers. Likewise, short sleepers had
      20% greater odds of being overweight or 57% greater odds of being obese. Long
      sleepers had 20% greater odds of being obese, but no greater odds of being
      overweight. CONCLUSIONS: Our findings support the hypothesis that prevalence of
      very short and short sleep has gradually increased over the last 32 years.
      Inadequate sleep was associated with overweight and obesity for each available
      year.

PMID- 24678586
TI  - Sulfidation kinetics of silver nanoparticles reacted with metal sulfides.
AB  - Recent studies have documented that the sulfidation of silver nanoparticles (Ag
      NP), possibly released to the environment from consumer products, occurs in
      anoxic zones of urban wastewater systems and that sulfidized Ag-NP exhibit
      dramatically reduced toxic effects. However, whether Ag-NP sulfidation also
      occurs under oxic conditions in the absence of bisulfide has not been addressed,
      yet. In this study we, therefore, investigated whether metal sulfides that are
      more resistant toward oxidation than free sulfide, could enable the sulfidation
      of Ag-NP under oxic conditions. We reacted citrate-stabilized Ag-NP of different
      sizes (10-100 nm) with freshly precipitated and crystalline CuS and ZnS in
      oxygenated aqueous suspensions at pH 7.5. The extent of Ag-NP sulfidation was
      derived from the increase in dissolved Cu(2+) or Zn(2+) over time and linked with
      results from X-ray absorption spectroscopy (XAS) analysis of selected samples.
      The sulfidation of Ag-NP followed pseudo first-order kinetics, with rate
      coefficients increasing with decreasing Ag-NP diameter and increasing metal
      sulfide concentration and depending on the type (CuS and ZnS) and crystallinity
      of the reacting metal sulfide. Results from analytical electron microscopy
      revealed the formation of complex sulfidation patterns that seemed to follow
      preexisting subgrain boundaries in the pristine Ag-NP. The kinetics of Ag-NP
      sulfidation observed in this study in combination with reported ZnS and CuS
      concentrations and predicted Ag-NP concentrations in wastewater and urban surface
      waters indicate that even under oxic conditions and in the absence of free
      sulfide, Ag-NP can be transformed into Ag2S within a few hours to days by
      reaction with metal sulfides. 

PMID- 24678587
TI  - Biting by Anopheles funestus in broad daylight after use of long-lasting
      insecticidal nets: a new challenge to malaria elimination.
AB  - BACKGROUND: Malaria control is mainly based on indoor residual spraying and
      insecticide-treated bed nets. The efficacy of these tools depends on the
      behaviour of mosquitoes, which varies by species. With resistance to
      insecticides, mosquitoes adapt their behaviour to ensure their survival and
      reproduction. The aim of this study was to assess the biting behaviour of
      Anopheles funestus after the implementation of long-lasting insecticidal nets
      (LLINs). METHODS: A study was conducted in Dielmo, a rural Senegalese village,
      after a second massive deployment of LLINs in July 2011. Adult mosquitoes were
      collected by human landing catch and by pyrethrum spray catch monthly between
      July 2011 and April 2013. Anophelines were identified by stereomicroscope and sub
      species by PCR. The presence of circumsporozoite protein of Plasmodium falciparum
      and the blood meal origin were detected by ELISA. RESULTS: Anopheles funestus
      showed a behavioural change in biting activity after introduction of LLINs,
      remaining anthropophilic and endophilic, while adopting diurnal feeding,
      essentially on humans. Six times more An. funestus were captured in broad
      daylight than at night. Only one infected mosquito was found during day capture.
      The mean of day CSP rate was 1.28% while no positive An. funestus was found in
      night captures. CONCLUSION: Mosquito behaviour is an essential component for
      assessing vectorial capacity to transmit malaria. The emergence of new
      behavioural patterns of mosquitoes may significantly increase the risk for
      malaria transmission and represents a new challenge for malaria control.
      Additional vector control strategies are, therefore, necessary.

PMID- 24678588
TI  - Two cases of cardiac device-related endocarditis due to Streptococcus
      dysgalactiae subsp. equisimilis (group C or G streptococci).
AB  - BACKGROUND: Cardiac device-related endocarditis is a very rare clinical
      manifestation of S. dysgalactiae subsp. equisimilis disease. This pathogen is a
      common cause of cellulitis. We here report two cases of cardiac device-related
      endocarditis due to Streptococcus dysgalactiae subsp. equisimilis. Blood cultures
      yielded this pathogen and both patients had recurrent bacteremia. Transthoracic
      and transesophageal echocardiography revealed lead vegetations. This is a new
      description of this pathogen to cause cardiac device-related endocarditis. CASE
      PRESENTATION: The first case is a 79-year-old finnish woman who received a dual
      chamber pacemaker for intermittent complete heart block in April 2011. She had
      three episodes of S. dysgalactiae subsp. equisimilis bacteremia. During first
      episode she had arthritis of glenohumeral joint. Focus was unknown in the second
      and third bacteremic episodes. During third bacteremic episode transesophageal
      echocardiography (TEE) revealed lead vegetation. Patient underwent successful
      complete system removal. She was treated with benzylpenicillin four million IU
      six times a day for four weeks intravenously. The second case is a 92-year-old
      finnish man. A dual-chamber pacemaker was implanted on June 2012 due to total
      heart block. He had recurrent S. dysgalactiae subsp. equisimilis bacteremia with
      cellulitis. During the second bacteremic episode transthoracic echocardiography
      (TTE) was performed because of persistent fever. Echocardiography revealed lead
      vegetation. Abdominal CT revealed also an abscess in the psoas region. This
      elderly patient was very fragile, and the pacemaker system was not extracted.
      Therapy was continued with benzylpenicillin four million IU six times a day for
      six weeks intravenously and thereafter suppressive treatment with amoksisillin
      500 mg three times a day was initiated. CONCLUSION: Streptococcus dysgalactiae
      subsp. equisimilis (group C and G streptococci) seldom cause cardiac device
      endocarditis. Both patients had recurrent bacteremia of S. dysgalactiae subsp.
      equisimilis and echocardiography revealed cardiac device-related endocarditis.
      These cases emphasize the importance of considering endocarditis in elderly
      persons having cardiac devices together with the presence of unexplained
      bacteremia, fever without focus or persistent fever.

PMID- 24678589
TI  - Gene expression profile of IGF1 and MSTN mRNA and their correlation with carcass
      traits in different breeds of geese at 70 d of age.
AB  - 1. The expression of insulin-like growth factor-1 (IGF1) and myostatin (MSTN)
      mRNA in breast and leg muscle was quantified in 70-d-old Taihu and Wanxi geese by
      using a Multiplex Competitive Fluorescent-PCR method and the correlations between
      mRNA levels and carcass traits were analysed. 2. IGF1 mRNA expression in breast
      muscle in Taihu geese was significantly higher than that in Wanxi geese and the
      MSTN mRNA level in leg muscle in Taihu geese was significantly higher than that
      in Wanxi geese. 3. There was no significant difference in breast muscle MSTN or
      leg muscle IGF1 mRNA expression between the two breeds. 4. Within the same breed,
      the IGF1 mRNA expression in leg muscle of male geese was significantly higher
      than that in female geese, and MSTN mRNA expression in leg muscle was
      significantly higher than that in breast muscle. 5. There was no difference in
      the IGF1 mRNA expression between tissues. 6. There was a positive correlation
      between IGF1 mRNA and MSTN mRNA and a negative correlation between IGF1 mRNA
      expression of breast muscle and leg muscle ratio. 7. In Wanxi geese, MSTN mRNA
      expression in leg muscle was negatively associated with body weight and leg
      muscle weight.

PMID- 24678591
TI  - Consistency of metagenomic assignment programs in simulated and real data.
AB  - BACKGROUND: Metagenomics is the genomic study of uncultured environmental
      samples, which has been greatly facilitated by the advent of shotgun-sequencing
      technologies. One of the main focuses of metagenomics is the discovery of
      previously uncultured microorganisms, which makes the assignment of sequences to
      a particular taxon a challenge and a crucial step. Recently, several methods have
      been developed to perform this task, based on different methodologies such as
      sequence composition or sequence similarity. The sequence composition methods
      have the ability to completely assign the whole dataset. However, their use in
      metagenomics and the study of their performance with real data is limited. In
      this work, we assess the consistency of three different methods (BLAST + Lowest
      Common Ancestor, Phymm, and Naive Bayesian Classifier) in assigning real and
      simulated sequence reads. RESULTS: Both in real and in simulated data, BLAST +
      Lowest Common Ancestor (BLAST + LCA), Phymm, and Naive Bayesian Classifier
      consistently assign a larger number of reads in higher taxonomic levels than in
      lower levels. However, discrepancies increase at lower taxonomic levels. In
      simulated data, consistent assignments between all three methods showed greater
      precision than assignments based on Phymm or Bayesian Classifier alone, since the
      BLAST + LCA algorithm performed best. In addition, assignment consistency in real
      data increased with sequence read length, in agreement with previously published
      simulation results. CONCLUSIONS: The use and combination of different approaches
      is advisable to assign metagenomic reads. Although the sensitivity could be
      reduced, the reliability can be increased by using the reads consistently
      assigned to the same taxa by, at least, two methods, and by training the programs
      using all available information.

PMID- 24678590
TI  - Fractionated radiotherapy is the main stimulus for the induction of cell death
      and of Hsp70 release of p53 mutated glioblastoma cell lines.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor
      in adults. Despite a multimodal therapy consisting of resection followed by
      fractionated radiotherapy (RT) combined with the chemotherapeutic agent (CT)
      temozolomide (TMZ), its recurrence is almost inevitable. Since the immune system
      is capable of eliminating small tumor masses, a therapy should also aim to
      stimulate anti-tumor immune responses by induction of immunogenic cell death
      forms. The histone deacetylase inhibitor valproic acid (VPA) might foster this.
      METHODS: Reflecting therapy standards, we applied in our in vitro model
      fractionated RT with a single dose of 2Gy and clinically relevant concentrations
      of CT. Not only the impact of RT and/or CT with TMZ and/or VPA on the clonogenic
      potential and cell cycle of the glioblastoma cell lines T98G, U251MG, and U87MG
      was analyzed, but also the resulting cell death forms and release of danger
      signals such as heat-shock protein70 (Hsp70) and high-mobility group protein B1
      (HMGB1). RESULTS: The clonogenic assays revealed that T98G and U251MG, having
      mutated tumor suppressor protein p53, are more resistant to RT and CT than U87MG
      with wild type (WT) p53. In all glioblastoma cells lines, fractionated RT induced
      a G2 cell cycle arrest, but only in the case of U87MG, TMZ and/or VPA alone
      resulted in this cell cycle block. Further, fractionated RT significantly
      increased the number of apoptotic and necrotic tumor cells in all three cell
      lines. However, only in U87MG, the treatment with TMZ and/or VPA alone, or in
      combination with fractionated RT, induced significantly more cell death compared
      to untreated or irradiated controls. While necrotic glioblastoma cells were
      present after VPA, TMZ especially led to significantly increased amounts of U87MG
      cells in the radiosensitive G2 cell cycle phase. While CT did not impact on the
      release of Hsp70, fractionated RT resulted in significantly increased
      extracellular concentrations of Hsp70 in p53 mutated and WT glioblastoma cells.
      CONCLUSIONS: Our results indicate that fractionated RT is the main stimulus for
      induction of glioblastoma cell death forms with immunogenic potential. The
      generated tumor cell microenvironment might be beneficial to include immune
      therapies for GBM in the future.

PMID- 24678592
TI  - Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud.
      show anti-Mayaro virus activity.
AB  - BACKGROUND: The arthropod-borne Mayaro virus (MAYV) causes 'Mayaro fever', a
      disease of medical significance, primarily affecting individuals in permanent
      contact with forested areas in tropical South America. Recently, MAYV has
      attracted attention due to its likely urbanization. Currently, there are no
      licensed drugs against most mosquito-transmitted viruses. Here, we investigated
      the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives
      from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. METHODS: Flavonoids
      were purified by chromatographic fractionation from leaf extracts of B.
      longifolia and chemically identified as quercetin and quercetin glycosides using
      spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n
      BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while
      their antiviral activity was evaluated by a virus yield inhibition assay.
      RESULTS: The following flavonoids were purified from B. longifolia leaves: non
      glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin,
      and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated
      the highest antiviral activity of all tested substances, while quercetin had the
      highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n
      BuOH fractions inhibited MAYV production by more than 90% at 25 MUg/mL,
      displaying a stronger antiviral effect than the licensed antiviral ribavirin. A
      mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect
      (IC90 = 104.9), while guaijaverin and quercitrin did not show significant
      antiviral activity. CONCLUSIONS: B. longifolia is a good source of flavonoids
      with anti-Mayaro virus activity. This is the first report of the activity of
      quercetin and its derivatives against an alphavirus.

PMID- 24678593
TI  - Association between polymorphisms in period genes and bone density in
      postmenopausal Korean women.
AB  - OBJECTIVE: In the present study, we aimed to investigate the association between
      genetic polymorphisms in period (PER) genes and bone mineral density (BMD) in
      postmenopausal Korean women. METHODS: The PER1 c.2247C> T and c.2884C> G
      polymorphisms; the PER2 c.661G> A and c.3731G> A polymorphisms; the PER3 c.2592G>
      A, c.3029C> T, c.3035C> T, and c.3083T> C polymorphisms, and the 54 bp variable
      number tandem repeats polymorphism were analyzed in 551 postmenopausal Korean
      women. Serum leptin, soluble leptin receptor, osteoprotegerin, soluble receptor
      activator of the nuclear factor-kappaB ligand, and bone markers including bone
      alkaline phosphatase and carboxy-terminal telopeptide of type I collagen were
      measured, and the lumbar spine and femoral neck BMDs were also determined.
      RESULTS: The PER2 c.661G> A, PER3 c.3029C> T and c.3035C> T polymorphisms were
      not observed. The PER2 and PER3 polymorphisms evaluated were not related to BMD,
      whereas associations of the c.2247C> T and c.2884C> G polymorphisms in PER1 with
      the lumbar spine BMD were observed both singly and in combination. The CC
      haplotype homozygotes showed significantly lower lumbar spine BMD than
      participants with other genotypes. Additionally, 2.01-fold higher odds for
      osteoporosis of the lumbar spine were found in the CC haplotype homozygotes
      compared to women not carrying the haplotype CC allele. No significant
      differences in bone markers were detected according to the PER1 haplotype
      genotype. CONCLUSIONS: Our results suggest that both the PER1 c.2247C> T and
      c.2884C> G polymorphisms may be genetic factors affecting the lumbar spine BMD in
      postmenopausal Korean women.

PMID- 24678594
TI  - Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and
      emphysema, but not mucus obstruction, in mice with cystic fibrosis-like lung
      disease.
AB  - RATIONALE: Recent evidence from clinical studies suggests that neutrophil
      elastase (NE) released in neutrophilic airway inflammation is a key risk factor
      for the onset and progression of lung disease in young children with cystic
      fibrosis (CF). However, the role of NE in the complex in vivo pathogenesis of CF
      lung disease remains poorly understood. OBJECTIVES: To elucidate the role of NE
      in the development of key features of CF lung disease including airway
      inflammation, mucus hypersecretion, goblet cell metaplasia, bacterial infection,
      and structural lung damage in vivo. METHODS: We used the Scnn1b-Tg mouse as a
      model of CF lung disease and determined effects of genetic deletion of NE (NE(-/
      )) on the pulmonary phenotype. Furthermore, we used novel Foerster resonance
      energy transfer (FRET)-based NE reporter assays to assess NE activity in
      bronchoalveolar lavage from Scnn1b-Tg mice and sputum from patients with CF.
      MEASUREMENTS AND MAIN RESULTS: Lack of NE significantly reduced airway
      neutrophilia, elevated mucin expression, goblet cell metaplasia, and distal
      airspace enlargement, but had no effect on airway mucus plugging, bacterial
      infection, or pulmonary mortality in Scnn1b-Tg mice. By using FRET reporters, we
      show that NE activity was elevated on the surface of airway neutrophils from
      Scnn1b-Tg mice and patients with CF. CONCLUSIONS: Our results suggest that NE
      plays an important role in the in vivo pathogenesis and may serve as a
      therapeutic target for inflammation, mucus hypersecretion, and structural lung
      damage and indicate that additional rehydration strategies may be required for
      effective treatment of airway mucus obstruction in CF.

PMID- 24678595
TI  - Management of patients with low back pain: a survey of French chiropractors.

PMID- 24678596
TI  - Riluzole effects on behavioral sensitivity and the development of axonal damage
      and spinal modifications that occur after painful nerve root compression.
AB  - OBJECT: Cervical radiculopathy is often attributed to cervical nerve root injury,
      which induces extensive degeneration and reduced axonal flow in primary
      afferents. Riluzole inhibits neuro-excitotoxicity in animal models of neural
      injury. The authors undertook this study to evaluate the antinociceptive and
      neuroprotective properties of riluzole in a rat model of painful nerve root
      compression. METHODS: A single dose of riluzole (3 mg/kg) was administered
      intraperitoneally at Day 1 after a painful nerve root injury. Mechanical
      allodynia and thermal hyperalgesia were evaluated for 7 days after injury. At Day
      7, the spinal cord at the C-7 level and the adjacent nerve roots were harvested
      from a subgroup of rats for immunohistochemical evaluation. Nerve roots were
      labeled for NF200, CGRP, and IB4 to assess the morphology of myelinated,
      peptidergic, and nonpeptidergic axons, respectively. Spinal cord sections were
      labeled for the neuropeptide CGRP and the glutamate transporter GLT-1 to evaluate
      their expression in the dorsal horn. In a separate group of rats,
      electrophysiological recordings were made in the dorsal horn. Evoked action
      potentials were identified by recording extracellular potentials while applying
      mechanical stimuli to the forepaw. RESULTS: Even though riluzole was administered
      after the onset of behavioral sensitivity at Day 1, its administration resulted
      in immediate resolution of mechanical allodynia and thermal hyperalgesia (p <
      0.045), and these effects were maintained for the study duration. At Day 7, axons
      labeled for NF200, CGRP, and IB4 in the compressed roots of animals that received
      riluzole treatment exhibited fewer axonal swellings than those from untreated
      animals. Riluzole also mitigated changes in the spinal distribution of CGRP and
      GLT-1 expression that is induced by a painful root compression, returning the
      spinal expression of both to sham levels. Riluzole also reduced neuronal
      excitability in the dorsal horn that normally develops by Day 7. The frequency of
      neuronal firing significantly increased (p < 0.045) after painful root
      compression, but riluzole treatment maintained neuronal firing at sham levels.
      CONCLUSIONS: These findings suggest that early administration of riluzole is
      sufficient to mitigate nerve root-mediated pain by preventing development of
      neuronal dysfunction in the nerve root and the spinal cord.

PMID- 24678597
TI  - Why do only a minority of men report severe levels of eating disorder
      symptomatology, when so many report substantial body dissatisfaction? Examination
      of exacerbating factors.
AB  - In recent years research employing female samples has indicated that although
      body dissatisfaction may be necessary for the onset of an eating disorder, it is
      not sufficient. This study examined body surveillance and difficulties in
      interpersonal domains (attachment anxiety and social anxiety) as potential
      moderators of the body dissatisfaction-eating disorder symptomatology
      relationship amongst Italian college men (N = 359). As expected, all examined
      variables were found to intensify this relationship such that body
      dissatisfaction was strongly related to men's eating disorder symptomatology when
      each moderator was at its highest level (i.e., 1 SD above the mean). Practical
      implications are discussed. 

PMID- 24678598
TI  - Teaching musculoskeletal examination skills to UK medical students: a comparative
      survey of Rheumatology and Orthopaedic education practice.
AB  - BACKGROUND: Specialists in Rheumatology and Orthopaedics are frequently involved
      in undergraduate teaching of musculoskeletal (MSK) examination skills. Students
      often report that specialty-led teaching is inconsistent, confusing and bears
      little resemblance to the curricula. The Gait, Arms, Legs and Spine (GALS) is a
      MSK screening tool that provides a standardised approach to examination despite
      it being fraught with disapproval and low uptake. Recent studies would appear to
      support innovative instructional methods of engaging learners such as patient
      educators and interactive small group teaching. METHODS: This comparative cross
      sectional survey evaluates the current state of undergraduate teaching in
      Rheumatology and Orthopaedics, including preferred teaching methods, attitudes
      towards GALS, and barriers to effective teaching. An electronic questionnaire was
      sent to specialist trainees and Consultants in the East and West Midlands region,
      representing 5 UK medical schools. Descriptive statistical data analysis was
      performed. RESULTS: There were 76 respondents representing 5 medical schools.
      There was a request for newer teaching methodologies to be used: multi-media
      computer-assisted learning (35.5%), audio-visual aids (31.6%), role-playing
      (19.7%), and social media (3.9%). It is evident that GALS is under-utilised with
      50% of clinicians not using GALS in their teaching. CONCLUSIONS: There is a
      genuine desire for clinical educators to improve their teaching ability,
      collaborate more with curriculum planners, and feel valued by institutions. There
      remains a call for implementing a standardised approach to MSK clinical teaching
      to supersede GALS.

PMID- 24678600
TI  - Helicobacter pylori: an overview on antimicrobials and drug delivery systems for
      its eradication.
AB  - Since the discovery of Helicobacter pylori (H. pylori) in the early 1980s, its
      eradication has been one of the most important global challenges in
      gastroenterology. Various circumstances make the treatment with antimicrobials
      particularly difficult. One problem has been that antibiotics commonly used were
      designed for the treatment of infections throughout the body rather than for
      delivering high concentrations locally within the stomach. Many gastroretentive
      dosage forms were developed in order to eradicate the infection, yet additional
      advancements are still needed to eliminate the infection completely and decrease
      its prevalence worldwide. An overview on different antimicrobials and a
      literature survey about different drug delivery systems used in eradication of H.
      pylori infection are presented in this review. 

PMID- 24678599
TI  - The involvement of the vasa vasorum in the development of vasculitis in animal
      model of Kawasaki disease.
AB  - BACKGROUND: Kawasaki Disease (KD) involves a diffuse and systemic vasculitis of
      unknown etiology that mainly affects infants and children. Although a
      considerable number of analyses of the clinical, histopathological and molecular
      biological details underlying the mechanism responsible for the development of
      coronary arterial lesions, it is still poorly understood.The purpose of this
      study was to analyze the state of angiogenesis, vasculogenesis and the
      distribution of blood vessels using an animal model of KD like vasculitis. We
      investigated the involvement of the vasa vasorum from the adventitia in the
      vascular involvement and the development of the disease state by performing
      sequential histopathology, scanning electron microscopy (SEM) and micro computed
      tomography (CT) studies using a murine model of vasculitis induced by the Candida
      albicans water-soluble fraction (CAWS). METHODS: To prepare the animal model of
      KD like vasculitis, CAWS was intraperitoneally injected into C57BL/6N mice for
      five consecutive days as reported by Ohno et al. We observed the changes of the
      vasa vasorum at the aorta and the orifices of the coronary arteries by SEM and
      micro CT, and also compared the neovascularization at the media and adventitia of
      the aorta by an immunohistochemical analysis. RESULTS: As previously reported,
      obvious inflammation was detected two weeks after the injection of CAWS, and also
      intimal thickening was observed three weeks after the injection. We found that
      the vasa vasorum in the adventitia of the aorta was increased in the model mice.
      The vasa vasorum started increasing one week after the injection of CAWS, before
      any obvious vasculitis was microscopically detected. CONCLUSION: The present
      results indicate that the vasculitis in Kawasaki disease starts as a disorder of
      the vasa vasorum.

PMID- 24678601
TI  - Parental perception of child's weight status and subsequent BMIz change: the
      KOALA birth cohort study.
AB  - BACKGROUND: Parents often fail to correctly perceive their children's weight
      status, but no studies have examined the association between parental weight
      status perception and longitudinal BMIz change (BMI standardized to a reference
      population) at various ages. We investigated whether parents are able to
      accurately perceive their child's weight status at age 5. We also investigated
      predictors of accurate weight status perception. Finally, we investigated the
      predictive value of accurate weight status perception in explaining children's
      longitudinal weight development up to the age of 9, in children who were
      overweight at the age of 5. METHODS: We used longitudinal data from the KOALA
      Birth Cohort Study. At the child's age of 5 years, parents filled out a
      questionnaire regarding child and parent characteristics and their perception of
      their child's weight status. We calculated the children's actual weight status
      from parental reports of weight and height at ages 2, 5, 6, 7, 8, and 9 years.
      Regression analyses were used to identify factors predicting which parents
      accurately perceived their child's weight status. Finally, regression analyses
      were used to predict subsequent longitudinal BMIz change in overweight children.
      RESULTS: Eighty-five percent of the parents of overweight children underestimated
      their child's weight status at age 5. The child's BMIz at age 2 and 5 were
      significant positive predictors of accurate weight status perception (vs.
      underestimation) in normal weight and overweight children. Accurate weight status
      perception was a predictor of higher future BMI in overweight children, corrected
      for actual BMI at baseline. CONCLUSIONS: Children of parents who accurately
      perceived their child's weight status had a higher BMI over time, probably making
      it easier for parents to correctly perceive their child's overweight. Parental
      awareness of the child's overweight as such may not be sufficient for subsequent
      weight management by the parents, implying that parents who recognize their
      child's overweight may not be able or willing to adequately manage the
      overweight.

PMID- 24678602
TI  - Modelling the effects of weather and climate on malaria distributions in West
      Africa.
AB  - BACKGROUND: Malaria is a leading cause of mortality worldwide. There is currently
      conflicting data and interpretation on how variability in climate factors affects
      the incidence of malaria. This study presents a hierarchical Bayesian modelling
      framework for the analysis of malaria versus climate factors in West Africa.
      METHODS: The hierarchical Bayesian framework takes into account spatiotemporal
      dependencies, and in this paper is applied to annual malaria and climate data
      from ten West African countries (Benin, Burkina Faso, Cote d'Ivoire, Gambia,
      Ghana, Liberia, Mali, Senegal, Sierra Leone, and Togo) during the period 1996
      2006. RESULTS: Results show a statistically significant correspondence between
      malaria rates and the climate variables considered. The two most important
      climate factors are found to be average annual temperature and total annual
      precipitation, and they show negative association with malaria incidence.
      CONCLUSIONS: This modelling framework provides a useful approach for studying the
      impact of climate variability on the spread of malaria and may help to resolve
      some conflicting interpretations in the literature.

PMID- 24678603
TI  - Epidemiologic characterization of 30 confirmed cases of human infection with
      avian influenza A(H7N9) virus in Hangzhou, China.
AB  - BACKGROUND: We examined the clinical and epidemiological characteristics of 30
      cases of human infection with avian influenza A(H7N9) virus in Hangzhou and
      investigated their external environments to provide evidence for contact tracing
      and disease prevention and control. METHODS: The cases confirmed from April 1
      through May 1, 2013 were studied. Field epidemiologic surveys were conducted to
      collect the clinical and epidemiologic data. Case-related and environmental
      specimens were collected for etiologic detection. RESULTS: Thirty cases of human
      infection with avian influenza A(H7N9) virus were confirmed in Hangzhou from
      April 1 through May 1, 2013, including one pregnant woman and three deaths. The
      median age of the patients was 62 years (range: 38-86 years). Twenty-three of the
      patients were men (76.67%). The median duration between disease onset and
      occurrence of respiratory failure and confirmed diagnosis was 5 and 6 days,
      respectively. Maximum medical observation of 666 close contacts of the patients
      revealed no irregularity. Of 314 external environmental specimens, the overall
      positive detection rate of H7N9 nucleic acid was 28.98%. Eight districts of
      Hangzhou city had positive detections in the external environments, the highest
      rate being in Yuhang District (78.13%). Statistical analysis of the specimen
      collection locations indicates a significant difference between the case-linked
      locations and the non-case locations (chi2 = 16.563, p < 0.05) in terms of H7N9
      viral nucleic acid detection rate. No epidemiologic link has been found among the
      30 cases. CONCLUSIONS: Most of the infected were retired individuals aged 60
      years or older. Men made the majority. The cases are sporadic at present, with no
      evidence of human-to-human transmission. Exposures to poultry and live poultry
      markets may be important sources of infection.

PMID- 24678604
TI  - Infection control interventions in small rural hospitals with limited resources:
      results of a cluster-randomized feasibility trial.
AB  - BACKGROUND: There are few reports on the feasibility of conducting successful
      infection control (IC) interventions in rural community hospitals. METHODS: Ten
      small rural community hospitals in Idaho and Utah were recruited to participate
      in a cluster-randomized trial of multidimensional IC interventions to determine
      their feasibility in the setting of limited resources. Five hospitals were
      randomized to develop individualized campaigns to promote HH, isolation
      compliance, and outbreak control. Five hospitals were randomized to continue with
      current IC practices. Regular blinded observations of hand hygiene (HH)
      compliance were conducted in all hospitals as the primary outcome measure.
      Additionally, periodic prevalence studies of patient colonization with resistant
      pathogens were performed. The 5-months intervention time period was compared to a
      4-months baseline period, using a multi-level logistic regression model. RESULTS:
      The intervention hospitals implemented a variety of strategies. The estimated
      average absolute change in "complete HH compliance" in intervention hospitals was
      20.1% (range, 7.8% to 35.5%) compared to -3.1% (range -6.3% to 5.9%) in control
      hospitals (p = 0.001). There was an estimated average absolute change in "any HH
      compliance" of 28.4% (range 17.8% to 38.2%) in intervention hospitals compared to
      0.7% (range -16.7 to 20.7%) in control hospitals (p = 0.010). Active surveillance
      culturing demonstrated an overall prevalence of MRSA carriage of 9.7%.
      CONCLUSIONS: A replicable intervention significantly improved hand hygiene as a
      primary outcome measure despite barriers of geographic distance and lack of
      experience with study protocols. Active surveillance culturing identified
      unsuspected reservoirs of MRSA colonization and further promoted IC activity.

PMID- 24678605
TI  - Evaluation of the efficacy of DDT indoor residual spraying and long-lasting
      insecticidal nets against insecticide resistant populations of Anopheles
      arabiensis Patton (Diptera: Culicidae) from Ethiopia using experimental huts.
AB  - BACKGROUND: Indoor Residual Spraying (IRS) and Long-Lasting Insecticidal nets
      (LLINs) are major malaria vector control tools in Ethiopia. However, recent
      reports from different parts of the country showed that populations of Anopheles
      arabiensis, the principal malaria vector, have developed resistance to most
      families of insecticides recommended for public health use which may compromise
      the efficacy of both of these key vector control interventions. Thus, this study
      evaluated the efficacy of DDT IRS and LLINs against resistant populations of An.
      arabiensis using experimental huts in Asendabo area, southwestern Ethiopia.
      METHODS: The susceptibility status of populations of An. arabiensis was assessed
      using WHO test kits to DDT, deltamethrin, malathion, lambda-cyhalothrin,
      fenitrothion and bendiocarb. The efficacy of LLIN (PermaNet 2.0), was evaluated
      using the WHO cone bioassay. Moreover, the effect of the observed resistance
      against malaria vector control interventions (DDT IRS and LLINs) were assessed
      using experimental huts. RESULTS: The findings of this study revealed that
      populations of An. arabiensis were resistant to DDT, deltamethrin, lambda
      cyhalothrin and malathion with mortality rates of 1.3%, 18.8%, 36.3% and 72.5%,
      respectively but susceptible to fenitrothion and bendiocarb with mortality rates
      of 98.81% and 97.5%, respectively. The bio-efficacy test of LLIN (PermaNet 2.0)
      against An. arabiensis revealed that the mosquito population showed moderate
      knockdown (64%) and mortality (78%). Moreover, mosquito mortalities in DDT
      sprayed huts and in huts with LLINs were not significantly different (p > 0.05)
      from their respective controls. CONCLUSION: The evaluation of the efficacy of DDT
      IRS and LLINs using experimental huts showed that both vector control tools had
      only low to moderate efficacy against An. arabiensis populations from Ethiopia.
      Despite DDT being replaced by carbamates for IRS, the low efficacy of LLINs
      against the resistant population of An. arabiensis is still a problem. Thus,
      there is a need for alternative vector control tools and implementation of
      appropriate insecticide resistance management strategies as part of integrated
      vector management by the national malaria control program.

PMID- 24678606
TI  - Feasibility and sustainability of an interactive team-based learning method for
      medical education during a severe faculty shortage in Zimbabwe.
AB  - BACKGROUND: In 2010, in the midst of the human immunodeficiency virus (HIV)
      epidemic in Zimbabwe, 69% of faculty positions in the Department of Medicine of
      the University of Zimbabwe College of Health Sciences (UZ-CHS) were vacant. To
      address the ongoing need to train highly skilled HIV clinicians with only a
      limited number of faculty, we developed and implemented a course for final-year
      medical students focused on HIV care using team-based learning (TBL) methods.
      METHODS: A competency-based HIV curriculum was developed and delivered to final
      year medical students in 10 TBL sessions as part of a 12 week clinical medicine
      attachment. A questionnaire was administered to the students after completion of
      the course to assess their perception of TBL and self-perceived knowledge gained
      in HIV care. Two cohorts of students completed the survey in separate academic
      years, 2011 and 2012. Descriptive analysis of survey results was performed.
      RESULTS: Ninety-six of 120 students (80%) completed surveys. One hundred percent
      of respondents agreed that TBL was an effective way to learn about HIV and 66%
      strongly agreed. The majority of respondents agreed that TBL was more stimulating
      than a lecture course (94%), fostered enthusiasm for the course material (91%),
      and improved teamwork (96%). Students perceived improvements in knowledge gained
      across all of the HIV subjects covered, especially in challenging applied
      clinical topics, such as management of HIV antiretroviral failure (88% with at
      least a "large improvement") and HIV-tuberculosis co-infection (80% with at least
      a "large improvement"). CONCLUSIONS: TBL is feasible as part of medical education
      in an African setting. TBL is a promising way to teach challenging clinical
      topics in a stimulating and interactive learning environment in a low-income
      country setting with a high ratio of students to teachers.

PMID- 24678607
TI  - An experimental study on thermal conductivity and viscosity of nanofluids
      containing carbon nanotubes.
AB  - Recently, there has been considerable interest in the use of nanofluids for
      enhancing thermal performance. It has been shown that carbon nanotubes (CNTs) are
      capable of enhancing the thermal performance of conventional working liquids.
      Although much work has been devoted on the impact of CNT concentrations on the
      thermo-physical properties of nanofluids, the effects of preparation methods on
      the stability, thermal conductivity and viscosity of CNT suspensions are not well
      understood. This study is focused on providing experimental data on the effects
      of ultrasonication, temperature and surfactant on the thermo-physical properties
      of multi-walled carbon nanotube (MWCNT) nanofluids. Three types of surfactants
      were used in the experiments, namely, gum arabic (GA), sodium dodecylbenzene
      sulfonate (SDBS) and sodium dodecyl sulfate (SDS). The thermal conductivity and
      viscosity of the nanofluid suspensions were measured at various temperatures. The
      results showed that the use of GA in the nanofluid leads to superior thermal
      conductivity compared to the use of SDBS and SDS. With distilled water as the
      base liquid, the samples were prepared with 0.5 wt.% MWCNTs and 0.25% GA and
      sonicated at various times. The results showed that the sonication time
      influences the thermal conductivity, viscosity and dispersion of nanofluids. The
      thermal conductivity of nanofluids was typically enhanced with an increase in
      temperature and sonication time. In the present study, the maximum thermal
      conductivity enhancement was found to be 22.31% (the ratio of 1.22) at
      temperature of 45 degrees C and sonication time of 40 min. The viscosity of
      nanofluids exhibited non-Newtonian shear-thinning behaviour. It was found that
      the viscosity of MWCNT nanofluids increases to a maximum value at a sonication
      time of 7 min and subsequently decreases with a further increase in sonication
      time. The presented data clearly indicated that the viscosity and thermal
      conductivity of nanofluids are influenced by the sonication time. Image analysis
      was carried out using TEM in order to observe the dispersion characteristics of
      all samples. The findings revealed that the CNT agglomerates breakup with
      increasing sonication time. At high sonication times, all agglomerates disappear
      and the CNTs are fragmented and their mean length decreases. 

PMID- 24678608
TI  - Differential meta-analysis of RNA-seq data from multiple studies.
AB  - BACKGROUND: High-throughput sequencing is now regularly used for studies of the
      transcriptome (RNA-seq), particularly for comparisons among experimental
      conditions. For the time being, a limited number of biological replicates are
      typically considered in such experiments, leading to low detection power for
      differential expression. As their cost continues to decrease, it is likely that
      additional follow-up studies will be conducted to re-address the same biological
      question. RESULTS: We demonstrate how p-value combination techniques previously
      used for microarray meta-analyses can be used for the differential analysis of
      RNA-seq data from multiple related studies. These techniques are compared to a
      negative binomial generalized linear model (GLM) including a fixed study effect
      on simulated data and real data on human melanoma cell lines. The GLM with fixed
      study effect performed well for low inter-study variation and small numbers of
      studies, but was outperformed by the meta-analysis methods for moderate to large
      inter-study variability and larger numbers of studies. CONCLUSIONS: The p-value
      combination techniques illustrated here are a valuable tool to perform
      differential meta-analyses of RNA-seq data by appropriately accounting for
      biological and technical variability within studies as well as additional study
      specific effects. An R package metaRNASeq is available on the CRAN (http://cran.r
      project.org/web/packages/metaRNASeq).

PMID- 24678609
TI  - Development of a colloidal gold-based lateral flow dipstick immunoassay for rapid
      qualitative and semi-quantitative analysis of artesunate and dihydroartemisinin.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT) plays an indispensable
      role in malaria control and elimination. However, the circulation of counterfeit,
      substandard drugs has greatly threatened malaria elimination campaigns. Most
      methods for the analysis of artemisinin and its derivatives require expensive
      equipment and sophisticated instrumentation. A convenient, easy-to-use diagnostic
      device for rapid evaluation of the quality of artemisinin drugs at the point-of
      care is still lacking. In this study a lateral flow dipstick immunoassay was
      developed for qualitative and semi-quantitative analysis of artesunate (ATS) and
      dihydroartemisinin (DHA) in anti-malarial drugs. METHODS: This assay was based on
      a monoclonal antibody (mAb) raised against ATS. ATS-bovine serum albumin and goat
      anti-mouse IgG, used as the test capture reagent and the control capture reagent,
      were coated on the nitrocellulose membrane to form the test line and control
      line, respectively. The conjugate pad was saturated with the gold-labelled anti
      ATS mAb. RESULTS: The indicator range of the dipsticks, defined as lowest
      concentration of the target analytes between which the test line was not visible,
      were 100-200 and 200-500 ng mL(-1) for ATS and DHA, respectively. No competitive
      inhibition was observed up to 5,000 ng mL(-1) of quinine, chloroquine diphosphate
      salt, primaquine phosphate, pyrimethamine, lumefantrine, amodiaquine, piperaquine
      tetraphosphate tetrahydrate or pyronaridine tetraphosphate. Semi-quantitative
      analysis of ATS and DHA in commercial drugs and raw drug materials with the
      dipsticks produced result agreeable with those determined by high performance
      liquid chromatography (HPLC). Storage test showed that the indicator range for
      artemisinins remained unchanged after a week at 37  degrees C and increased four
      folds after six months of storage at 4  degrees C or ambient temperature.
      CONCLUSIONS: The new selected mAb 3D82G7 with high avidity and broad cross
      reactivity for artemisinins was used to develop and optimize a dipstick
      immunoassay for qualitative and semi-quantitative analysis of ATS and DHA in anti
      malarial drugs. The semi-quantitative analysis of ATS and DHA in commercial drugs
      and raw drug materials, and the specificity test of the artemisinin-related drugs
      both proved the accurate performance of the developed dipsticks for semi
      quantitation of ACT samples. The dipstick may be used as a point-of-care device
      for identifying substandard and counterfeit ATS- and DHA-containing anti-malarial
      drugs.

PMID- 24678610
TI  - Do low-income neighbourhoods have the least green space? A cross-sectional study
      of Australia's most populous cities.
AB  - BACKGROUND: An inequitable distribution of parks and other 'green spaces' could
      exacerbate health inequalities if people on lower incomes, who are already at
      greater risk of preventable diseases, have poorer access. METHODS: The
      availability of green space within 1 kilometre of a Statistical Area 1 (SA1) was
      linked to data from the 2011 Australian census for Sydney (n = 4.6 M residents);
      Melbourne (n = 4.2 M); Brisbane (n = 2.2 M); Perth (n = 1.8 M); and Adelaide (n =
      1.3 M). Socioeconomic circumstances were measured via the percentage population
      of each SA1 living on < $21,000 per annum. Negative binomial and logit regression
      models were used to investigate association between the availability of green
      space in relation to neighbourhood socioeconomic circumstances, adjusting for
      city and population density. RESULTS: Green space availability was substantively
      lower in SA1s with a higher percentage of low income residents (e.g. an incidence
      rate ratio of 0.82 (95% confidence interval (95% CI) 0.75, 0.89) was observed for
      SA1s containing >=20% versus 0-1% low income residents). This association varied
      between cities (p < 0.001). Adelaide reported the least equitable distribution of
      green space, with approximately 20% greenery in the most affluent areas versus
      12% availability in the least affluent. Although Melbourne had a smaller
      proportion of SA1s in the top quintile of green space availability (13.8%), the
      distribution of greenery was the most equitable of all the cities, with only a
      0.5% difference in the availability of green space between SA1s containing 0-1%
      low income households versus those with >=20%. Inequity of access, however, was
      reported across all cities when using logit regression to examine the
      availability of at least 20% (odds ratio 0.74, 95% CI 0.59, 0.93) or 40% (0.45,
      0.29, 0.69) green space availability in the more disadvantaged versus affluent
      neighbourhoods. CONCLUSION: Affirmative action on green space planning is
      required to redress the socioeconomic inequity of access to this important public
      health resource.

PMID- 24678611
TI  - Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae.
AB  - BACKGROUND: KPC-producing carbapenem-resistant Klebsiella pneumoniae (CRKP)
      infections are associated with high mortality; however, their virulence
      determinants are not well defined. METHODS: We investigated the virulence and
      plasmid transferability among KPC-containing K. pneumoniae isolates. RESULTS: KPC
      2 and -3 were successfully conjugated and retained by a virulent K2 K. pneumoniae
      recipient isolate. Antimicrobial susceptibility testing showed KPC-2 and -3 donor
      strains were resistant to more than four classes of antibiotics while the K2
      isolate was only initially resistant to ampicillin. After conjugation of KPC-2
      and -3, the K2 K. pneumoniae transconjugants became resistant to all beta
      lactams. Additionally, the KPC K2 K. pneumoniae transconjugants continued to
      retain its high serum resistance and murine lethality. CONCLUSIONS: Conjugation
      and retainment of KPC by virulent K2 K. pneumoniae and the ability of the
      tranconjugants to maintain its high serum resistance and murine lethality after
      conjugation was demonstrated in this study. These findings are concerning for the
      potential of KPC-like genes to disseminate among virulent K. pneumoniae isolates.

PMID- 24678612
TI  - Effect of combining mosquito repellent and insecticide treated net on malaria
      prevalence in Southern Ethiopia: a cluster-randomised trial.
AB  - BACKGROUND: A mosquito repellent has the potential to prevent malaria infection,
      but there has been few studies demonstrating the effectiveness of combining this
      strategy with the highly effective long-lasting insecticidal nets (LLINs). This
      study aimed to determine the effect of combining community-based mosquito
      repellent with LLINs in the reduction of malaria. METHODS: A community-based
      clustered-randomised trial was conducted in 16 rural villages with 1,235
      households in southern Ethiopia between September and December of 2008. The
      villages were randomly assigned to intervention (mosquito repellent and LLINs,
      eight villages) and control (LLINs alone, eight villages) groups. Households in
      the intervention villages received mosquito repellent (i.e., Buzz-Off petroleum
      jelly, essential oil blend) applied every evening. The baseline survey was
      followed by two follow-up surveys, at one month interval. The primary outcome was
      detection of Plasmodium falciparum, Plasmodium vivax, or both parasites, through
      microscopic examination of blood slides. Analysis was by intention to treat.
      Baseline imbalances and clustering at individual, household and village levels
      were adjusted using a generalized linear mixed model. RESULTS: 3,078 individuals
      in intervention and 3,004 in control group were enrolled into the study. Compared
      with the control arm, the combined use of mosquito repellent and LLINs
      significantly reduced malaria infection of all types over time [adjusted Odds
      Ratio (aOR) = 0.66; 95% CI = 0.45-0.97]. Similarly, a substantial reduction in P.
      falciparum malaria infection during the follow-up surveys was observed in the
      intervention group (aOR = 0.53, 95% CI = 0.31-0.89). The protective efficacy of
      using mosquito repellent and LLINs against malaria infection of both P.
      falciparum/P. vivax and P. falciparum was 34% and 47%, respectively. CONCLUSIONS:
      Daily application of mosquito repellent during the evening followed by the use of
      LLINs during bedtime at community level has significantly reduced malaria
      infection. The finding has strong implication particularly in areas where malaria
      vectors feed mainly in the evening before bedtime. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01160809.

PMID- 24678614
TI  - Treatment of mild and moderate type-2 diabetes: open prospective trial with
      Hintonia latiflora extract.
AB  - BACKGROUND: Extracts from the bark of Hintonia latiflora are used as dietetic
      measures to support the regulation of glucose metabolism and the stabilization of
      blood glucose values. METHODS: A dry concentrated extract from the bark of
      Hintonia latiflora in capsule form was tested in an open, prospective clinical
      study in 41 dietetically stabilized subjects with type 2 diabetes. The effects on
      parameters of blood glucose control were documented over a period of six months.
      RESULTS: Fasting and postprandial glucose and the HbA1c value declined
      significantly. In the case of HbA1c, this meant a reduction of the absolute value
      from 7.49 +/- 0.72% to 6.82 +/- 0.67% (from 58.4 to 51.0 mmol/mol Hb; intention
      to treat (ITT) population). Furthermore, cholesterol and triglycerides were
      slightly reduced and no negative effect on other laboratory parameters and no
      change of the liver values were observed. Tolerance was very good. In particular,
      no side effects and no hypoglycemic episodes or worsening of diabetic symptoms
      occurred. CONCLUSIONS: The study confirms the positive effect of extracts from
      the bark of Hintonia latiflora on blood glucose values suggesting a potential
      benefit in the management of glucose metabolism in cases of type 2 diabetes.
      TRIAL REGISTRATION: Reg.-No. ISRCTN83308122.

PMID- 24678613
TI  - Ethical issues evolving from patients' perspectives on compulsory screening for
      syphilis and voluntary screening for cervical cancer in Kenya.
AB  - BACKGROUND: Public health aims to provide universal safety and progressive
      opportunities to populations to realise their highest level of health through
      prevention of disease, its progression or transmission. Screening asymptomatic
      individuals to detect early unapparent conditions is an important public health
      intervention strategy. It may be designed to be compulsory or voluntary depending
      on the epidemiological characteristics of the disease. Integrated screening,
      including for both syphilis and cancer of the cervix, is a core component of the
      national reproductive health program in Kenya. Screening for syphilis is
      compulsory while it is voluntary for cervical cancer. Participants' perspectives
      of either form of screening approach provide the necessary contextual information
      that clarifies mundane community concerns. METHODS: Focus group discussions with
      female clients screened for syphilis and cancer of the cervix were conducted to
      elicit their perspectives of compulsory and voluntary screening. The discussions
      were audiotaped, transcribed and thematic content analysis performed manually to
      explore emerging ethics issues. RESULTS: The results indicate that real ethical
      challenges exist in either of the approaches. Also, participants were more
      concerned about the benefits of the procedure and whether their dignity is
      respected than the compulsoriness of screening per se. The implication is for the
      policy makers to clarify in the guidelines how to manage ethical challenges,
      while at the operational level, providers need to be judicious to minimize
      potential harms participants and families when screening for disease in women.
      CONCLUSIONS: The context for mounting screening as a public health intervention
      and attendant ethical issues may be more complex than hitherto perceived.
      Interpreting emerging ethics issues in screening requires more nuanced
      considerations of individuals' contextual experiences since these may be
      contradictory to the policy position. In considering mounting screening for
      Syphilis and cervical cancer as a public heal intervention, the community
      interests and perspectives should be inculcated into the program. Population lack
      of information on procedures may influence adversely the demand for screening
      services by the individuals at risk or the community as a collective agent.

PMID- 24678616
TI  - Living on the edge: reconstructing the genetic history of the Finnish wolf
      population.
AB  - BACKGROUND: Many western European carnivore populations became almost or
      completely eradicated during the last ~200 years, but are now recovering.
      Extirpation of wolves started in Finland in the 19th century, and for more than
      150 years the population size of wolves has remained small. To investigate
      historical patterns of genetic variation, we extracted DNA from 114 wolf samples
      collected in zoological museums over the last ~150 years. Fifteen microsatellite
      loci were used to look at genotypic variation in this historical sample.
      Additionally, we amplified a 430 bp sequence of mtDNA control region from the
      same samples. Contemporary wolf samples (N = 298) obtained after the population
      recovery in the mid-1990s, were used as a reference. RESULTS: Our analyses of
      mtDNA revealed reduced variation in the mtDNA control region through the loss of
      historical haplotypes observed prior to wolf declines. Heterozygosity at
      autosomal microsatellite loci did not decrease significantly. However, almost 20%
      of microsatellite alleles were unique to wolves collected before the 1960s. The
      genetic composition of the population changed gradually with the largest changes
      occurring prior to 1920. Half of the oldest historical samples formed a
      distinguishable genetic cluster not detected in the modern-day Finnish or Russian
      samples, and might therefore represent northern genetic variation lost from
      today's gene pool. Point estimates of Ne were small (13.2 and 20.5) suggesting
      population fragmentation. Evidence of a genetic population bottleneck was also
      detected. CONCLUSIONS: Our genetic analyses confirm changes in the genetic
      composition of the Finnish wolf population through time, despite the geographic
      interconnectivity to a much larger population in Russia. Our results emphasize
      the need for restoration of the historical connectivity between the present wolf
      populations to secure long-term viability. This might be challenging, however,
      because the management policies between Western and Eastern Europe often differ
      greatly. Additionally, wolf conservation is still a rather controversial issue,
      and anthropogenic pressure towards wolves remains strong.

PMID- 24678615
TI  - Addressing the needs of traumatic brain injury with clinical proteomics.
AB  - BACKGROUND: Neurotrauma or injuries to the central nervous system (CNS) are a
      serious public health problem worldwide. Approximately 75% of all traumatic brain
      injuries (TBIs) are concussions or other mild TBI (mTBI) forms. Evaluation of
      concussion injury today is limited to an assessment of behavioral symptoms, often
      with delay and subject to motivation. Hence, there is an urgent need for an
      accurate chemical measure in biofluids to serve as a diagnostic tool for
      invisible brain wounds, to monitor severe patient trajectories, and to predict
      survival chances. Although a number of neurotrauma marker candidates have been
      reported, the broad spectrum of TBI limits the significance of small cohort
      studies. Specificity and sensitivity issues compound the development of a
      conclusive diagnostic assay, especially for concussion patients. Thus, the
      neurotrauma field currently has no diagnostic biofluid test in clinical use.
      CONTENT: We discuss the challenges of discovering new and validating identified
      neurotrauma marker candidates using proteomics-based strategies, including
      targeting, selection strategies and the application of mass spectrometry (MS)
      technologies and their potential impact to the neurotrauma field. SUMMARY: Many
      studies use TBI marker candidates based on literature reports, yet progress in
      genomics and proteomics have started to provide neurotrauma protein profiles.
      Choosing meaningful marker candidates from such 'long lists' is still pending, as
      only few can be taken through the process of preclinical verification and large
      scale translational validation. Quantitative mass spectrometry targeting specific
      molecules rather than random sampling of the whole proteome, e.g., multiple
      reaction monitoring (MRM), offers an efficient and effective means to multiplex
      the measurement of several candidates in patient samples, thereby omitting the
      need for antibodies prior to clinical assay design. Sample preparation challenges
      specific to TBI are addressed. A tailored selection strategy combined with a
      multiplex screening approach is helping to arrive at diagnostically suitable
      candidates for clinical assay development. A surrogate marker test will be
      instrumental for critical decisions of TBI patient care and protection of
      concussion victims from repeated exposures that could result in lasting
      neurological deficits.

PMID- 24678617
TI  - Interplay between temperature-activated vibrations and nondipolar effects in the
      valence excitations of the CO2 molecule.
AB  - We report a study on the temperature dependence of the valence electron
      excitation spectrum of CO2 performed using nonresonant inelastic X-ray scattering
      spectroscopy. The excitation spectra were measured at the temperatures of 300 and
      850 K with momentum-transfer values of 0.4-4.8 A(-1), i.e., from the dipole limit
      to the higher-multipole regime, and were simulated using high-level coupled
      cluster calculations on the dipole and quadrupole level. The results demonstrate
      the emergence of dipole-forbidden excitations owing to temperature-induced
      bending mode activation and finite momentum transfer. 

PMID- 24678618
TI  - Cerclage, progesterone and alpha-hydroxyprogeterone caproate treatment in women
      at risk for preterm delivery.
AB  - The most significant action of progesterone appears to be on the cervix and in
      prevention rather than on treatment of preterm delivery. In women with singleton
      gestations, no prior PTB, and CL <20 mm at <24 weeks, vaginal progesterone,
      either 90 mg gel or 200 mg suppository, is associated with reduction of both
      preterm birth (PTB) and perinatal morbidity/mortality. Cerclage is as effective
      as vaginal progesterone in women with CL <25 mm. Treatment of women with previous
      PTB with 17OHP-C from 16 to 20 weeks' gestation until 36 weeks could reduce
      significantly both the risk of delivery at <37, <35 and <32 weeks' gestation, as
      well as the rates of NEC, the need for supplemental oxygen and IVH. In women
      successfully treated with tocolytics progesterone combined with corticosteroid
      therapy lengthens pregnancy, reduces occurrence of respiratory distress syndrome
      and low birth weight. However, there is currently insufficient evidence on the
      role of progesterone after arrested preterm labor. It is reasonable to support an
      approach with CL screening of women with prior PTB starting at 16 to 19 weeks and
      administration of progesterone to women with a short cervix. Cerclage may be
      offered to those with a CL<25 mm. A combination of traditional tocolytics,
      corticosteroids and progesterone might be beneficial.

PMID- 24678620
TI  - Detergent-compatible proteases: microbial production, properties, and stain
      removal analysis.
AB  - Proteases are one of the most important commercial enzymes used in various
      industrial domains such as detergent and leather industries. The alkaline
      proteases as well as other detergent-compatible enzymes such as lipases and
      amylases serve now as the key components in detergent formulations. They break
      down various stains during fabric washing. The search for detergent-compatible
      proteases with better properties is a continuous exercise. The current trend is
      to use detergent-compatible proteases that are stable over a wide temperature
      range. Although the proteases showing stability at elevated pH have the capacity
      to be used in detergent formulations, their usage can be significant if they are
      also stable and compatible with detergent and detergent ingredients, and also
      able to remove protein stains. Despite the existence of some reviews on alkaline
      proteases, there is no specification for the use of alkaline proteases as
      detergent additives. The present review describes the detergent-compatible
      proteases tested as detergent additives. An overview was provided for screening,
      optimization, purification, and properties of detergent compatible proteases,
      with an emphasis on the stability and compatibility of the alkaline proteases
      with the detergent and detergent compounds, as well as stain removal examination
      methods. 

PMID- 24678619
TI  - mAChRs activation induces epithelial-mesenchymal transition on lung epithelial
      cells.
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) has been proposed as a
      mechanism in the progression of airway diseases and cancer. Here, we explored the
      role of acetylcholine (ACh) and the pathway involved in the process of EMT, as
      well as the effects of mAChRs antagonist. METHODS: Human lung epithelial cells
      were stimulated with carbachol, an analogue of ACh, and epithelial and
      mesenchymal marker proteins were evaluated using western blot and
      immunofluorescence analyses. RESULTS: Decreased E-cadherin expression and
      increased vimentin and alpha-SMA expression induced by TGF-beta1 in alveolar
      epithelial cell (A549) were significantly abrogated by the non-selective mAChR
      antagonist atropine and enhanced by the acetylcholinesterase inhibitor
      physostigmine. An EMT event also occurred in response to physostigmine alone.
      Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF
      beta1. Interestingly, ACh analogue carbachol also induced EMT in A549 cells as
      well as in bronchial epithelial cells (16HBE) in a time- and concentration
      dependent manner, the induction of carbachol was abrogated by selective
      antagonist of M1 (pirenzepine) and M3 (4-DAMP) mAChRs, but not by M2
      (methoctramine) antagonist. Moreover, carbachol induced TGF-beta1 production from
      A549 cells concomitantly with the EMT process. Carbachol-induced EMT occurred
      through phosphorylation of Smad2/3 and ERK, which was inhibited by pirenzepine
      and 4-DAMP. CONCLUSIONS: Our findings for the first time indicated that mAChR
      activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo
      EMT and provided insights into novel therapeutic strategies for airway diseases
      in which lung remodeling occurs.

PMID- 24678621
TI  - Cortical vein thrombosis in a case of idiopathic thrombocytopenic purpura.

PMID- 24678622
TI  - Tolvaptan for the treatment of liver cirrhosis oedema.
AB  - No alternative therapeutic option exists if liver cirrhosis patients have
      insufficient response to conventional diuretics and/or experience conventional
      diuretic-related adverse events. In 2013, tolvaptan (7.5 mg/day), an arginine
      vasopressin V2 receptor antagonist, was approved in Japan for the treatment of
      liver cirrhosis with oedema. Short-term use of tolvaptan produced decreases in
      body weight, reduction in ascites volume and increases in urine volume when
      compared to placebo, despite the use of conventional diuretics. Additionally,
      approximately 60% of patients with oedema-related symptoms improved. Low-dose
      tolvaptan, 3.75 mg, was also efficacious. Even in patients with low serum albumin
      (<2.5 g/dL), decrease in body weight was greater with tolvaptan than with
      placebo. For future research, the efficacy and safety of lower tolvaptan doses
      for the treatment of liver cirrhosis patients with oedema should be confirmed in
      Japan. The results of this research could be used as an indicator or a guideline
      for physicians around the world. 

PMID- 24678624
TI  - Analysis of isotopic signals in the Danube River water at Tulln, Austria, based
      on daily grab samples in 2012.
AB  - Results of stable isotope measurements (delta(2)H, delta(18)O) of daily grab
      samples, taken from the Danube River at Tulln (river km 1963) during 2012, show
      seasonal and short-term variations depending on the climatic/hydrological
      conditions and changes in the catchment area (temperature changes, heavy rains
      and snow melt processes). Isotope ratios in river water clearly reflect the
      isotopic composition of precipitation water in the catchment area since
      evaporation influences play a minor role. Average delta(2)H and delta(18)O values
      in 2012 are-780/00 and-11.00/00, respectively, deuterium excess averages 100/00.
      The entire variation amounts to 1.80/00 in delta(18)O and 150/00 in delta(2)H.
      Quick changes of the isotopic composition within a few days emphasise the
      necessity of daily sampling for the investigation of hydrological events, while
      monthly grab sampling seems sufficient for the investigation of long-term hydro
      climatic trends. (3)H results show peaks (half-width 1-2 days, up to about 150
      TU) exceeding the regional environmental level of about 9 TU, probably due to
      releases from nuclear power plants. 

PMID- 24678625
TI  - Facile synthesis of Z-alkenes via uphill catalysis.
AB  - Catalytic access to thermodynamically less stable Z-alkenes has recently received
      considerable attention. These approaches have relied upon kinetic control of the
      reaction to arrive at the thermodynamically less stable geometrical isomer.
      Herein, we present an orthogonal approach which proceeds via photochemically
      catalyzed isomerization of the thermodynamic E-alkene to the less stable Z-isomer
      which occurs via a photochemical pumping mechanism. We consider two potential
      mechanisms. Importantly, the reaction conditions are mild, tolerant, and
      operationally simple and will be easily implemented. 

PMID- 24678626
TI  - Pathogenicity and molecular characteristics of infectious bronchitis virus (IBV)
      strains isolated from broilers showing diarrhoea and respiratory disease.
AB  - Abstract 1. The possibility that infectious bronchitis virus (IBV) variants
      isolated from broilers with enteric and respiratory problems have a different
      tropism and pathological outcome from those IBV strains causing classical
      respiratory disease was investigated. 2. IBV variants were isolated from broiler
      flocks with enteric and respiratory problems in two regions of Brazil. The USP-10
      isolate, of enteric origin, was inoculated via the oral oroculonasal routes into
      IBV-antibody-free broilers and specific pathogen-free (SPF) chickens to determine
      tissue tropism and pathogenicity and compared with an IBV variant (USP-50)
      isolated from chickens showing signs of respiratory disease only. 3. Both USP-10
      and USP-50 strains caused similar pathological patterns by either route of
      inoculation. Both variants were detected in respiratory and non-respiratory
      tissues, including the kidney, intestine and testis. 4. Broilers were more
      susceptible to infection than SPF chickens, and seroconversion was detected in
      all of the chicks. 

PMID- 24678627
TI  - Polyelectrolyte-stabilized graphene oxide liquid crystals against salt, pH, and
      serum.
AB  - Stabilization of colloids is of great significance in nanoscience for their
      fundamental research and practical applications. Electrostatic repulsion
      stabilized anisotropic colloids, such as graphene oxide (GO), can form stable
      liquid crystals (LCs). However, the electrostatic field would be screened by
      ions. To stabilize colloidal LCs against electrolyte is an unsolved challenge.
      Here, an effective strategy is proposed to stabilize GO LCs under harsh
      conditions by association of polyelectrolytes onto GO sheets. Using sodium
      poly(styrene sulfonate) (PSS) and poly[2-(methacryloyloxy)ethyl]dimethyl-(3
      sulfopropyl)ammonium hydroxide (PMEDSAH), a kind of polyzwitterion, GO LCs were
      well-maintained in the presence of NaCl (from 0 M to saturated), extreme pH (from
      1 to 13), and serum. Moreover, PSS- or PMEDSAH-coated chemically reduced GO (rGO)
      also showed stability against electrolyte. 

PMID- 24678628
TI  - Screening: The information individuals need to support their decision: per
      protocol analysis is better than intention-to-treat analysis at quantifying
      potential benefits and harms of screening.
AB  - BACKGROUND: Providing individuals with the information necessary to make informed
      decisions is now considered an ethical standard for health systems and general
      practitioners. DISCUSSION: Results from intention-to-treat analysis have thus far
      been used to illustrate screening benefits and harms, but intention-to-treat
      analysis in most screening trials compares no intervention to invitation to
      screening. Therefore, the intervention arm includes everyone who was invited,
      regardless of actual participation. These results may be misleading for
      individual decision-making. We propose to use a per protocol analysis that
      includes all subjects who presented to screening and compares them to those in
      control arm, adjusting for self-selection bias. Such an analysis can give more
      accurate and useful information for individual decision-making. SUMMARY: Correct
      information for individual decision to participate in screening or not should
      consider the efficacy, benefits, and harms observed for subjects who actually
      participated at least once in screening compared to the control arm, adjusting
      for self-selection bias. Thus, per protocol analysis, even a very conservative
      one, should be used, not a full intention-to-treat analysis.

PMID- 24678629
TI  - Transmigration and phagocytosis of macrophages in an airway infection model using
      four-dimensional techniques.
AB  - During infection, recruited phagocytes transmigrate across the epithelium to
      remove the pathogens deposited on the airway surface. However, it is difficult to
      directly observe cellular behaviors (e.g., transmigration) in single-cell layer
      cultures or in live animals. Combining a three-dimensional (3D) cell coculture
      model mimicking airway infection with time-lapse confocal imaging as a four
      dimensional technique allowed us to image the behaviors of macrophages in 3D over
      time. The airway infection model was moved to a glass-bottomed dish for live-cell
      imaging by confocal laser scanning microscopy. Using time-lapse confocal imaging,
      we recorded macrophages transmigrating across the polyethylene terephthalate
      (PET) membrane of the inserts through the 5-MUm pores in the PET membrane.
      Macrophages on the apical side of the insert exhibited essentially three types of
      movements, one of which was transmigrating across the epithelial cell monolayer
      and arriving at the surface of monolayer. We found that adding Staphylococcus
      aureus to the model increased the transmigration index but not the transmigration
      time of the macrophages. Only in the presence of S. aureus were the macrophages
      able to transmigrate across the epithelial cell monolayer. Apical-to-basal
      transmigration of macrophages was visualized dynamically. We also imaged the
      macrophages phagocytizing S. aureus deposited on the surface of the monolayer in
      the airway infection model. This work provides a useful tool to study the
      cellular behaviors of immune cells spatially and temporally during infection. 

PMID- 24678630
TI  - A critical review of traditional Chinese medicine use amongst women with
      menopausal symptoms.
AB  - OBJECTIVES: To provide the first critical review of traditional Chinese medicine
      (TCM) use amongst symptomatic menopausal women, drawing upon work examining the
      perspectives of both TCM users and TCM practitioners. METHODS: A search was
      conducted in three English-language databases (MEDLINE, CINAHL and AMED) and
      three Chinese-language databases (CNKI, VIP and CBM Disc) for 2002-2013
      international peer-reviewed articles reporting empirical findings of TCM use in
      menopause. RESULTS: A total of 25 journal articles reporting 22 studies were
      identified as meeting the review inclusion criteria. Chinese herbal medicine
      appears to be the most common therapy amongst symptomatic menopausal women, and
      vasomotor symptoms and emotional changes are the most frequent symptoms for which
      TCM is sought. However, evidence regarding the prevalence of TCM use and users'
      profile in menopause is limited. Existing studies are of varied methodological
      quality, often reporting low response rate, extensive recall bias and a lack of
      syndrome differentiation. CONCLUSIONS: This review provides insights for
      practitioners and health policy-makers regarding TCM care to symptomatic
      menopausal women. More nationally representative studies are required to
      rigorously examine TCM use for the management of menopausal symptoms. Syndrome
      differentiation of menopausal women is an area which also warrants further
      attention.

PMID- 24678632
TI  - Slow biotransformation of carbon nanotubes by horseradish peroxidase.
AB  - Due to steady increase in use and mass production carbon nanotubes (CNTs) will
      inevitably end up in the environment. Because of their chemical nature CNTs are
      expected to be recalcitrant and biotransform only at very slow rates. Degradation
      of CNTs within days has recently been reported, but excluding one study,
      conclusions relied solely on qualitative results. We incubated 13 different types
      of CNTs and subjected them to enzymatic oxidation with horseradish peroxidase and
      concluded that the analytical methods commonly employed for studying degradation
      of CNTs did not have the sensitivity to unequivocally demonstrate degradation of
      these materials. To obtain unambiguous results with regard to the
      biotransformability of CNTs in the horseradish peroxidase system we incubated:
      (a) (14)C-labeled multiwalled CNTs, homologous to Baytubes CNTs; and (b) (13)C
      depleted single-walled CNTs, used in previous studies. Our results show that
      (14)C-CO2 evolved linearly at a rate of about 0.020/00 per day, and at the end of
      the 30-day incubations the CO2 evolved amounted to about 0.50/00 of both initial
      substrates, the (14)C-labeled multiwalled and (13)C-depleted single-walled CNTs.
      These results clearly show that CNT material is oxidized in the horseradish
      peroxidase system but with half-lives of about 80 years and not a few days as has
      been reported before. Adequately addressing biotransformation rates of CNTs is
      key toward a better understanding of the fate of these materials in the
      environment. 

PMID- 24678631
TI  - Monitoring, characterization and control of chronic, symptomatic malaria
      infections in rural Zambia through monthly household visits by paid community
      health workers.
AB  - BACKGROUND: Active, population-wide mass screening and treatment (MSAT) for
      chronic Plasmodium falciparum carriage to eliminate infectious reservoirs of
      malaria transmission have proven difficult to apply on large national scales
      through trained clinicians from central health authorities. METHODOLOGY: Fourteen
      population clusters of approximately 1,000 residents centred around health
      facilities (HF) in two rural Zambian districts were each provided with three
      modestly remunerated community health workers (CHWs) conducting active monthly
      household visits to screen and treat all consenting residents for malaria
      infection with rapid diagnostic tests (RDT). Both CHWs and HFs also conducted
      passive case detection among residents who self-reported for screening and
      treatment. RESULTS: Diagnostic positivity was higher among symptomatic patients
      self-reporting to CHWs (42.5%) and HFs (24%) than actively screened residents
      (20.3%), but spatial and temporal variations of diagnostic positivity were highly
      consistent across all three systems. However, most malaria infections (55.6%)
      were identified through active home visits by CHWs rather than self-reporting to
      CHWs or HFs. Most (62%) malaria infections detected actively by CHWs reported one
      or more symptoms of illness. Most reports of fever and vomiting, plus more than a
      quarter of history of fever, headache and diarrhoea, were attributable to malaria
      infection. The minority of residents who participated >12 times had lower rates
      of malaria infection and associated symptoms in later contacts but most residents
      were tested <4 times and high malaria diagnostic positivity (32%) in active
      surveys, as well as incidence (1.7 detected infections per person per year)
      persisted in the population. Per capita cost for active service delivery by CHWs
      was US$5.14 but this would rise to US$10.68 with full community compliance with
      monthly testing at current levels of transmission, and US$6.25 if pre-elimination
      transmission levels and negligible treatment costs were achieved. CONCLUSION:
      Monthly active home visits by CHWs equipped with RDTs were insufficient to
      eliminate the human infection reservoir in this typical African setting, despite
      reasonably high LLIN/IRS coverage. However, dramatic impact upon infection and
      morbidity burden might be attainable and cost-effective if community
      participation in regular testing could be improved and the substantial, but not
      necessarily prohibitive, costs are affordable to national programmes.

PMID- 24678633
TI  - Phylogeny and virulence divergency analyses of Toxoplasma gondii isolates from
      China.
AB  - BACKGROUND: Toxoplasma gondii (T. gondii) is a very successful parasite that can
      infect virtually all warm blooded animals with a worldwide distribution. It
      causes a large range of clinical manifestations in both humans and domesticated
      animals. In addition, marked biological differences exist among T. gondii strains
      in the pathogenicity and geographical distribution. Molecular epidemiology
      studies primarily based on restriction fragment length polymorphism (RFLP) method
      revealed that three main types are predominant in North America and Europe,
      whereas other diverse genotypes are found in other parts of the world.
      Microsatellite (MS) as a type of genetic marker has been widely used in many
      organisms. Limited MS genotyping, however, to fingerprint T. gondii isolates has
      been reported and little is known about the MS data of the strains predominantly
      prevalent in China. METHODS: Genotyping of twenty-eight Chinese T. gondii
      isolates were performed using 15 MS markers located on 12 different chromosomes.
      Results were analyzed in terms of population structure by a Bayesian statistical
      approach. Phylogenetic analysis was obtained from a Neighbor-Net phylogenetic
      network. The virulence analyses of some representative isolates were determined
      by inoculation of mice and cell invasion assays. The gene expressions of some
      virulence-associated factors (VFs) were performed by quantitative real-time PCR
      (qRT- PCR). RESULTS: Three haplogroups were clustered among the 28 isolates
      although minor genetic differences were found within haplogroups. The majority of
      strains belong to one haplogroup corresponding to the previously described
      Chinese 1 type (ToxoDB#9). Phylogenetic networks uncovered a limited diversity of
      T. gondii strains and the virulence differs in the strains sharing the same
      genotype. No remarkable difference, however, was noted in the tested VFs except
      for dense granule protein3 (GRA3), which was found to have a higher expression in
      low virulent TgCtwh6 (Wh6) strain than that in high virulent TgCtwh3 (Wh3)
      strain. CONCLUSION: The profile of microsatellite typing data from Chinese T.
      gondii strains revealed a limited genetic diversity and the selected VFs and
      phylogenetic network analyses displayed less divergence, although the strain
      virulence differs in the Chinese 1 type of T. gondii predominantly prevalent in
      China.

PMID- 24678635
TI  - The relationship among critical inner voices, low self-esteem, and self-criticism
      in eating disorders.
AB  - Hilde Bruch (1978) was one of the first to describe the phenomenon of anorectic
      patients experiencing a critical inner voice. Although several qualitative
      studies regarding eating disorder patients report this experience, few
      quantitative studies have been conducted in which hearing voices was examined in
      eating disorder patients. This motivated us to investigate whether eating
      disorder patients (N = 74) experience critical inner voices significantly more
      often than a healthy control group (N = 58). Is voice hearing related to the
      severity of the eating disorder and to low self-esteem and high self-criticism?
      These questions will be addressed in this article. 

PMID- 24678634
TI  - Mephedrone alters basal ganglia and limbic neurotensin systems.
AB  - Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that
      alters pre-synaptic dopamine (DA) activity like many psychostimulants. However,
      little is known about the post-synaptic dopaminergic impacts of mephedrone. The
      neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and
      limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity
      affects NT tissue levels. This study evaluated how mephedrone alters basal
      ganglia and limbic system NT content and the role of NT receptor activation in
      drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT
      content in basal ganglia (striatum, substantia nigra and globus pallidus) and the
      limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection)
      only increased striatal NT content. Mephedrone-induced increases in basal ganglia
      NT levels were mediated by D1 -like receptors in the striatum and the substantia
      nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone
      increased substance P content, another neuropeptide, in the globus pallidus, but
      not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist
      PD149163 blocked mephedrone self-administration, suggesting reduced NT release,
      as indicated by increased tissue levels, likely contributing to patterns of
      mephedrone consumption.

PMID- 24678636
TI  - Cooperative effects and optimal halogen bonding motifs for self-assembling
      systems.
AB  - Halogen bonding, due to its directionality and tunable strength, is being
      increasingly utilized in self-assembling materials and crystal engineering. Using
      density functional theory (DFT) and molecular mechanics (OPLS/CM1Ax)
      calculations, multiply halogen bonded complexes of brominated imidazole and
      pyridine are investigated along with their potential in construction of self
      assembling architectures. Dimers with 1-10 halogen bonds are considered and
      reveal maximal binding energies of 3-36 kcal/mol. Cooperative (nonadditive)
      effects are found in complexes that extend both along and perpendicular to the
      halogen bonding axes, with interaction energies depending on polarization,
      secondary interactions, and ring spacers. Four structural motifs were identified
      to yield optimal halogen bonding. For the largest systems, the excellent
      agreement found between the DFT and OPLS/CM1Ax results supports the utility of
      the latter approach for analysis and design of self-assembling supramolecular
      structures. 

PMID- 24678637
TI  - Distinct transthyretin oxidation isoform profile in spinal fluid from patients
      with Alzheimer's disease and mild cognitive impairment.
AB  - BACKGROUND: Transthyretin (TTR), an abundant protein in cerebrospinal fluid
      (CSF), contains a free, oxidation-prone cysteine residue that gives rise to TTR
      isoforms. These isoforms may reflect conditions in vivo. Since increased
      oxidative stress has been linked to neurodegenerative disorders such as
      Alzheimer's disease (AD) it is of interest to characterize CSF-TTR isoform
      distribution in AD patients and controls. Here, TTR isoforms are profiled
      directly from CSF by an optimized immunoaffinity-mass spectrometry method in 76
      samples from patients with AD (n = 37), mild cognitive impairment (MCI, n = 17)),
      and normal pressure hydrocephalus (NPH, n = 15), as well as healthy controls (HC,
      n = 7). Fractions of three specific oxidative modifications (S-cysteinylation, S
      cysteinylglycinylation, and S-glutathionylation) were quantitated relative to the
      total TTR protein. Results were correlated with diagnostic information and with
      levels of CSF AD biomarkers tau, phosphorylated tau, and amyloid beta1-42
      peptide. RESULTS: Preliminary data highlighted the high risk of artifactual TTR
      modification due to ex vivo oxidation and thus the samples for this study were
      all collected using strict and uniform guidelines. The results show that TTR is
      significantly more modified on Cys(10) in the AD and MCI groups than in controls
      (NPH and HC) (p <= 0.0012). Furthermore, the NPH group, while having normal TTR
      isoform distribution, had significantly decreased amyloid beta peptide but normal
      tau values. No obvious correlations between levels of routine CSF biomarkers for
      AD and the degree of TTR modification were found. CONCLUSIONS: AD and MCI
      patients display a significantly higher fraction of oxidatively modified TTR in
      CSF than the control groups of NPH patients and HC. Quantitation of CSF-TTR
      isoforms thus may provide diagnostic information in patients with dementia
      symptoms but this should be explored in larger studies including prospective
      studies of MCI patients. The development of methods for simple, robust, and
      reproducible inhibition of in vitro oxidation during CSF sampling and sample
      handling is highly warranted. In addition to the diagnostic information the
      possibility of using TTR as a CSF oxymeter is of potential value in studies
      monitoring disease activity and developing new drugs for neurodegenerative
      diseases.

PMID- 24678638
TI  - Posterior lumbar interbody fusion with stand-alone Trabecular Metal cages for
      repeatedly recurrent lumbar disc herniation and back pain.
AB  - OBJECT: Patients with recurrent sciatica due to repeated reherniation of the
      intervertebral disc carry a poor prognosis for recovery and create a large burden
      on society. There is no consensus about the best treatment for this patient
      group. The goal of this study was to evaluate the 12-month results of the
      placement of stand-alone Trabecular Metal cages in these patients. METHODS: The
      authors performed a retrospective analysis of 26 patients with recurrent disc
      herniations treated with stand-alone posterior lumbar interbody fusion (PLIF)
      with Trabecular Metal cages. At 1 year patients were evaluated using the Roland
      Morris Disability Questionnaire (RMDQ) and a visual analog scale (VAS) for back
      and leg pain. Furthermore, Likert scores of perceived recovery and satisfaction
      with the treatment were recorded. Lumbar spine radiographs after 1 year were
      compared with postoperative radiographs to measure subsidence. Stability of the
      operated segment was assessed using dynamic radiography. RESULTS: The patient
      group consisted of 26 patients (62% male) with a mean age of 45.7 +/- 11.4 years
      (+/- SD). Patients had a history of 1 (31%), 2 (42%), or more (27%) discectomies
      at the same level. The mean follow-up period was 15.3 +/- 7.3 months. At follow
      up the mean VAS score for pain in the affected leg was 36.7 +/- 27.9. The mean
      VAS score for back pain was 42.5 +/- 30.2. The mean RMDQ score at follow-up was
      9.8 +/- 6.2. Twelve (46%) of the 26 patients had a global perceived good
      recovery. With respect to treatment satisfaction, 18 patients (69%) were content
      or very content with the operation and would recommend it. Disc height was
      increased immediately postoperatively, and at the 1-year follow-up it was still
      significantly higher compared with the preoperative height (mean 41% +/- 38.7%,
      range -25.7 to 126.8, paired t-test, both p < 0.001), although a mean of 7.52% +/
      11.6% subsidence occurred (median 2.0% [interquartile range 0.0%-10.9%], p <
      0.003). No significant correlation between subsidence and postoperative back pain
      was found (Spearman's rho -0.2, p = 0.459). Flexion-extension radiographs showed
      instability in 1 patient. CONCLUSIONS: Although only 46% of patients reported a
      good recovery with significant reductions in back and leg pain, 85% of patients
      reported at least some benefit from the operation, and a marked improvement in
      working status at follow-up was noted. In view of previously published poor
      results of instrumented lumbar fusion for patients with failed back surgery
      syndrome, the present data indicate that Trabecular Metal interbody fusion cages
      can be used in a stand-alone fashion and should not always need supplemental
      posterior fixation in patients with recurrent disc herniation without spinal
      instability, although a long-term follow-up study is warranted.

PMID- 24678639
TI  - "Tripping out" with the TRP superfamily and TRPV1 for novel neuroprotection.

PMID- 24678640
TI  - The C-terminal domain of the utrophin tandem calponin-homology domain appears to
      be thermodynamically and kinetically more stable than the full-length protein.
AB  - Domains are in general less stable than the corresponding full-length proteins.
      Human utrophin tandem calponin-homology (CH) domain seems to be an exception.
      Reversible, equilibrium denaturant melts indicate that the isolated C-terminal
      domain (CH2) is thermodynamically more stable than the tandem CH domain. Thermal
      melts show that CH2 unfolds at a temperature higher than that at which the full
      length protein unfolds. Stopped-flow kinetics indicates that CH2 unfolds slower
      than the full-length protein, indicating its higher kinetic stability. Thus, the
      utrophin tandem CH domain may be one of the few proteins in which an isolated
      domain is more stable than the corresponding full-length protein. 

PMID- 24678641
TI  - Renal artery stenosis due to neurofibromatosis type 1: case report and literature
      review.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a relatively common autosomal
      dominant disorder. The most common vascular abnormality in patients with NF1 is
      bilateral or unilateral renal artery stenosis. CASE REPORT: A 16-year-old boy
      presented with a headache of 4-year duration and was found to be moderately
      hypertensive. On physical examination, axillary freckling and multiple cafe-au
      lait spots were revealed over the trunk, while numerous small nodules were
      palpable on the limbs. Biopsy of subcutaneous nodule showed neurofibroma. Lisch
      nodules were identified on slit-lamp examination and grade I hypertensive
      retinopathy was present on fundoscopy. Clinical laboratory investigations
      revealed that renal and liver function tests, blood cells count, urinalysis,
      serum electrolytes, serum levels of renin and aldosterone, and 24-hour urine
      levels of catecholamines were all within normal ranges. Abdominal ultrasound and
      CT were normal. Both kidneys were of normal size. CT angiography showed right
      renal artery stenosis (>90%) at the ostium. The final diagnosis of NF1 with right
      renal artery stenosis and secondary hypertension was then made. The patient was
      treated with Procardin (30 mg/d) and improved with a significant decline in blood
      pressure. The main outcomes were to control blood pressure without necessarily
      proceeding with PTRA. We also present a review of the literature. CONCLUSIONS:
      NF1 may present with hypertension due to renal artery stenosis in children. All
      young patients (<30 year) with hypertension should be clinically screened for
      secondary causes of hypertension, including NF1, so that renal revascularization
      can be offered before permanent end organ damage has occurred. First-line
      management using medication alone could be appropriate, keeping the
      interventional options for when the patient's condition deteriorates.

PMID- 24678642
TI  - Barriers to gene exchange in hybridizing field crickets: the role of male
      courtship effort and cuticular hydrocarbons.
AB  - BACKGROUND: Pre-zygotic barriers often involve some form of sexual selection,
      usually interpreted as female choice, as females are typically the choosier sex.
      However, males typically show some mate preferences, which are increasingly
      reported. Here we document previously uncharacterized male courtship behavior
      (effort and song) and cuticular hydrocarbon (CHC) profiles in the hybridizing
      crickets Gryllus firmus and G. pennsylvanicus. These two species exhibit multiple
      barriers to gene exchange that act throughout their life history, including a
      behavioral barrier that results in increased time to mate in heterospecific
      pairs. RESULTS: We demonstrated that male mate choice (as courtship effort
      allocation) plays a more important role in the prezygotic behavioral barrier than
      previously recognized. In gryllids females ultimately decide whether or not to
      mate, yet we found males were selective by regulating courtship effort intensity
      toward the preferred (conspecific) females. Females were also selective by mating
      with more intensely courting males, which happened to be conspecifics. We report
      no differences in courtship song between the two species and suggest that the
      mechanism that allows males to act differentially towards conspecific and
      heterospecific females is the cuticular hydrocarbon (CHC) composition. CHC
      profiles differed between males and females of both species, and there were clear
      differences in CHC composition between female G. firmus and G. pennsylvanicus but
      not between the males of each species. CONCLUSION: Although many barriers to gene
      exchange are known in this system, the mechanism behind the mate recognition
      leading to reduced heterospecific mating remains unknown. The CHC profiles might
      be the phenotypic cue that allow males to identify conspecifics and thus to
      adjust their courtship intensity accordingly, leading to differential mating
      between species.

PMID- 24678643
TI  - Effects of benazepril on functional activity of endothelial progenitor cells from
      hypertension patients.
AB  - The effect of angiotensin-converting enzyme inhibitors on hypertension patients
      regarding endothelial progenitor cell (EPC) functions is poorly understood. The
      aim of this study was to investigate the effects of benazepril on the
      proliferation, adhesion and migration capacity of EPCs and its possible
      mechanism. The functions of EPCs from hypertension patients were obviously
      reduced compared with control group, and this could be improved by benazepril in
      a dose-dependent manner, whereas this improvement were obviously blocked when
      AMD3100 were used together. Therefore, benazepril could obviously improve
      functions of EPCs from hypertension patients, and the potential mechanism may be
      related to SDF-1/CXCR4 axis.

PMID- 24678644
TI  - Access to functionalized bicyclo[4,3,0]nonenes via palladium-catalyzed oxidative
      cyclization of 2-allylcyclohexyl oximes.
AB  - A new palladium-catalyzed oxidative cyclization process leading to the
      functionalized bicyclo[4,3,0]nonenes is serendipitously discovered during
      attempts to form aza-heterocycle by the amino-Heck reaction of trans-2
      vinylclohexyl phosphinyloxime. Under the influence of Pd(dba)2/Et3N/1:1 N2-O2
      (1:1, v/v) (Method A) or Pd(OAc)2/Et3N/O2 (Method B), the reactions afford the
      substituted cis-1-hydroxyl-8-formyl-bicyclo[4,3,0]non-8(9)-enes or
      bicycle[4,3,0]non-1(9)-en-8-ones in varying yields with the incorporation of
      molecular oxygen into the structures. The 5,6-bicyclic scaffold of these products
      is presumably derived from tandem double intramolecular cyclization followed by
      the ring-opening of an aza-palladium(II) tricyclic intermediate.

PMID- 24678645
TI  - Rheumatology clinicians' experiences of brief training and implementation of
      skills to support patient self-management.
AB  - BACKGROUND: Self-management of arthritis requires informed, activated patients to
      manage its physical and psychosocial consequences. Patient activation and self
      management can be enhanced through the use of cognitive-behavioural approaches,
      which have a strong evidence base and provide insight into the variation in
      outcome of patients with ostensibly the same degree of disease activity. However,
      training for rheumatology health professionals in theory and skills underpinning
      the facilitation of self-management is not widely available. To develop such
      training, this study explored rheumatology clinicians' experiences of a variety
      of brief skills training courses to understand which aspects were helpful or
      unhelpful, and to identify the barriers and facilitators of applying the skills
      in clinical practice. METHODS: 16 clinicians who had previously attended
      communication and self-management skills training participated in semi-structured
      interviews: 3 physicians, 3 physiotherapists, 4 nurses, 6 occupational
      therapists. Transcripts were analysed (ED) using a hybrid inductive and deductive
      thematic approach, with a subset independently analysed (SH, RG-H, RJ). RESULTS:
      3 overarching themes captured views about training undertaken and subsequent use
      of approaches to facilitate self-management. In 'putting theory into practice',
      clinicians felt that generic training was not as relevant as rheumatology
      specific training. They wanted a balance between theory and skills practice, and
      identified the importance of access to ongoing support. In 'challenging
      professional identity', models of care and working cultures influenced learning
      and implementation. Training often challenged a tendency to problem-solve on
      behalf of patients and broadened clinicians' remit from a primary focus on
      physical symptoms to the mind and body interaction. In 'enhanced practice',
      clinicians viewed consultations as enhanced after training. Focus had shifted
      from clinicians' agendas to those of patients, and clinicians reported eliciting
      patients' priorities and the use of theoretically-driven strategies such as goal
      setting. CONCLUSIONS: To varying extents, clinicians were able to learn and
      implement new approaches to support patient self-management after brief training.
      They believed that cognitive behavioural and communication skills to facilitate
      self-management enhanced their practice. To optimise self-management support in
      routine care brief, skills-based, rheumatology-specific training needs to be
      developed, alongside ongoing clinical supervision. Further research should
      examine patients' perspectives of care based on these approaches.

PMID- 24678647
TI  - Delayed, severe thrombocytemia after abciximab infusion for primary angioplasty
      in acute coronary syndromes: Moving between systemic bleeding and stent
      thrombosis.

PMID- 24678646
TI  - Natural history of colonization with methicillin-resistant Staphylococcus aureus
      (MRSA) and vancomycin-resistant Enterococcus (VRE): a systematic review.
AB  - BACKGROUND: No published systematic reviews have assessed the natural history of
      colonization with methicillin-resistant Staphylococcus aureus (MRSA) or
      vancomycin-resistant Enterococcus (VRE). Time to clearance of colonization has
      important implications for patient care and infection control policy. METHODS: We
      performed parallel searches in OVID Medline for studies that reported the time to
      documented clearance of MRSA and VRE colonization in the absence of treatment,
      published between January 1990 and July 2012. RESULTS: For MRSA, we screened 982
      articles, identified 16 eligible studies (13 observational studies and 3
      randomized controlled trials), for a total of 1,804 non-duplicated subjects. For
      VRE, we screened 284 articles, identified 13 eligible studies (12 observational
      studies and 1 randomized controlled trial), for a total of 1,936 non-duplicated
      subjects. Studies reported varying definitions of clearance of colonization; no
      study reported time of initial colonization. Studies varied in the frequency of
      sampling, assays used for sampling, and follow-up period. The median duration of
      total follow-up was 38 weeks for MRSA and 25 weeks for VRE. Based on pooled
      analyses, the model-estimated median time to clearance was 88 weeks after
      documented colonization for MRSA-colonized patients and 26 weeks for VRE
      colonized patients. In a secondary analysis, clearance rates for MRSA and VRE
      were compared by restricting the duration of follow-up for the MRSA studies to
      the maximum observed time point for VRE studies (43 weeks). With this
      restriction, the model-fitted median time to documented clearance for MRSA would
      occur at 41 weeks after documented colonization, demonstrating the sensitivity of
      the pooled estimate to length of study follow-up. CONCLUSIONS: Few available
      studies report the natural history of MRSA and VRE colonization. Lack of a
      consistent definition of clearance, uncertainty regarding the time of initial
      colonization, variation in frequency of sampling for persistent colonization,
      assays employed and variation in duration of follow-up are limitations of the
      existing published literature. The heterogeneity of study characteristics limits
      interpretation of pooled estimates of time to clearance, however, studies
      included in this review suggest an increase in documented clearance over time, a
      result which is sensitive to duration of follow-up.

PMID- 24678649
TI  - Umbilical cord serum lipids between early and late clamping in full-term
      newborns. A systematic assignment treatment group.
AB  - OBJECTIVE: The aim of the current study was to determine any relationship between
      the timing of clamping of the umbilical cord and the lipid levels circulating in
      umbilical artery and vein. METHODS: We studied a clinical trial with systematic
      assignment in 229 single-fetus full-term deliveries with normal gestational
      course and spontaneous delivery; out of these, 111 were subjected to early
      clamping (EC, within 10 s of delivery) and 118 to late clamping (LC, at 2 min).
      In all cases, total cholesterol (TC), triglycerides (TG), and phospholipids were
      measured in sera from umbilical artery and vein. RESULTS: TC and TG values were
      significantly higher in the EC group than in the LC group in both umbilical
      artery and vein. Comparing values between umbilical artery and vein in the two
      clamping groups, in the EC group, all studied lipids TC, TG and phospholipids
      were significantly higher in vein than in artery. In the LC group, only TC was
      higher in vein. CONCLUSION: Umbilical cord lipid levels are related to the timing
      of umbilical cord clamping, finding which is noteworthy, because they are
      essential component of postnatal development. Our study confirms that delivery
      acts as an important modifier of fetal lipid levels.

PMID- 24678648
TI  - Evaluation of the ability of cervical length and fetal fibronectin measurement to
      predict preterm delivery in asymptomatic women with risk factors.
AB  - OBJECTIVE: To evaluate the power of transvaginal ultrasound cervical length (CL)
      and fetal fibronectin (fFN) measurement for the prediction of preterm delivery
      (PTD) in asymptomatic women with risk factors. METHODS: Between January 2010 and
      October 2012, 218 women with singleton pregnancies and a high risk for PTD (i.e.
      prior history of PTD, cervical surgeries, late miscarriages, uterine
      abnormalities or premature rupture of the membranes) were selected. CL was
      measured by transvaginal ultrasonography between 14 and 22 weeks, and a CL<2.5 cm
      was considered to be short. The fFN was measured with a sterile speculum
      examination. The primary outcome was the spontaneous PTD rate at <34(+0) and
      <37(+0) weeks, and the PTD rate was analyzed by either of two methods alone or
      combined. RESULTS: There were 213 cases included in the analysis, and 47 women
      (22.1%) had positive fFN. The average CL of women with positive fFN (2.3 +/- 0.9
      cm) was significantly shorter than that of women with negative fFN (3.1 +/- 0.8
      cm; p=0.02). There were 25 (11.7%) and 38 (18.8%) cases with PTD at <34(+0) and
      <37(+0) weeks, respectively. By individual analyses, the highest PTD rate was
      51.2% in women with positive fFN at <37(+0) weeks. The sensitivity and diagnostic
      efficiency values for PTD prediction by CL were low at <34(+0) and <37(+0) weeks.
      The values of diagnostic efficiency by fFN were >80% at <34(+0) and <37(+0)
      weeks. In the combined analysis, the highest PTD rate was 57.1% in women with CL
      <= 2.5 cm and positive fFN at <37(+0) weeks. The Kaplan-Meier curve indicated
      that there were significant differences among the four groups (chi(2)=54.261;
      p=0.000). CONCLUSIONS: These results indicate a significant correlation between
      fFN and PTD prediction. The PTD prediction could be enhanced by combined CL and
      fFN measurement.

PMID- 24678650
TI  - Obstetrical and neonatal outcomes in renal transplant recipients.
AB  - OBJECTIVE: To measure the incidence and outcomes of pregnancies in renal
      transplant (RT) patients and to identify risk factors of adverse pregnancy
      outcomes. METHODS: We conducted a population-based retrospective cohort study
      using the United States Nationwide Inpatient Sample from 2003-2010. The incidence
      of pregnancies in women with RT was measured and logistic regression analysis was
      used to estimate the adjusted effect of RT on maternal and fetal outcomes.
      RESULTS: We identified 375 deliveries in patients with a RT among 7094300 births
      for an overall incidence of 5.3 cases per 100000 births over 8 years. Maternal
      complications, including preeclampsia OR=9.87 (7.76, 12.55) and blood transfusion
      OR=2.29 (1.69, 3.12) were more common in women with RT as compared to in women
      without. RT pregnancies were also complicated by an increased risk of preterm
      birth OR=4.65 (3.72, 5.81), intrauterine fetal death OR=3.67 (1.89, 7.15) and
      fetal congenital anomalies OR=5.28 (2.81, 9.90). Among women with RT and pre
      existing hypertension, the risk of intrauterine growth restriction (IUGR) was
      considerably increased from 4.3% to 21.8%, OR=3.79 (1.67, 8.62). CONCLUSION:
      Pregnancies in RT patients are associated with an increased risk of maternal and
      fetal morbidities. Among women with RT, pre-existing hypertension strongly
      increases the risk of IUGR.

PMID- 24678651
TI  - Investigating the effects of a family-centered care program on stroke patients'
      adherence to their therapeutic regimens.
AB  - Abstract Background: Stroke survivors have residual neurological impairment,
      which requires long-term support and care. In this situation family involvement
      in care process is necessary. However, as the family caregivers of stroke
      survivors are not necessarily supported by the health-care professionals, and
      they often feel inadequately prepared to deal with the physical, cognitive and
      emotional needs of the stroke survivors. Aim: The aim of this study was to
      investigate the effects of a family-centered care program on stroke patients'
      adherence to their therapeutic regimens. Methods: This is a posttest-only
      randomized controlled trial study, conducted on stroke patients and their family
      care-givers. The control group (n = 30) received only routine hospital services
      and the experimental group (n = 30) received routine hospital services plus a
      family-centered care program consisting of four steps; need assessment, educating
      families based on patients' needs, follow-ups by short phone interviews, and
      referral service. The data were collected via a demographic data form and
      "Adherence to the therapeutic regimens" Questionnaire between July 2011 to March
      2012 and lasted two months for each subject. Data were assessed and analyzed with
      SPSS version 18. Findings: Study findings showed that the levels of adherence to
      the different components of the therapeutic regimens, including rehabilitations,
      medications and dietary regimen are significantly higher in the experimental
      group compared to the control group (P value< 0.001). Conclusion: By empowering
      patients' families and improving their adherence to the therapeutic regimens,
      family-centered care programs will be able to play an important role in
      management of physical and mental health of stroke patients.

PMID- 24678652
TI  - Developing immunologically inert adeno-associated virus (AAV) vectors for gene
      therapy: possibilities and limitations.
AB  - Gene therapy has become a clinical reality as demonstrated by remarkable benefits
      seen in Phase I/II clinical trials for hemophilia B, lipoprotein lipase
      deficiency and Leber's congenital amarousis. The choice of, and the improved
      understanding in vector characteristics have contributed significantly to this
      success. The adeno-associated virus (AAV) vectors used in these trials have been
      long known to be relatively safe and efficacious. However, certain factors, most
      notably host immunity to the vector, prevent their widespread use. In patients
      who have pre-existing antibodies to AAV, these vectors will be rapidly cleared.
      Administration of a relatively high initial dose of vector to achieve and sustain
      a higher margin of therapeutic benefit is limited by concerns of vector dose
      dependent T cell response. Frequent vector administration necessitated by the non
      integrating nature of the virus is difficult due to the variable, yet significant
      host immunological memory. Thus generation of AAV vectors that are
      immunologically inert is pivotal for the long-term success with this promising
      vector system. Several strategies, that aim targeted disruption of antigenic
      sites or those that chemically modify the vectors have been proposed for host
      immune evasion. While these approaches have been successful in the pre-clinical
      model systems, this continues to be a field of intense experimentation and
      constant improvisation due to limited information available on vector immunology
      or data from human studies. This review forms a comprehensive report on current
      strategies available to generate immunologically inert AAV vectors and their
      potential in mediating longterm gene transfer. 

PMID- 24678653
TI  - Effect of phosphoric acid pretreatment of corncobs on the fermentability of
      Clostridium beijerinckii TISTR 1461 for biobutanol production.
AB  - Corncobs pretreated with H2SO4, HNO3, and H3PO4 were compared to evaluate the
      fermentation ability of Clostridium beijerinckii TISTR 1461 to produce biobutanol
      via acetone-butanol-ethanol (ABE) fermentation. It was found that the hydrolysate
      from H3PO4 pretreatment could be used as a substrate without any inhibitor
      removal methods. However, in terms of sugar yield, it gave the lowest total
      sugars in both pretreatment and enzymatic hydrolysis. Response surface
      methodology was applied to optimize enzymatic hydrolysis of the pretreated
      corncobs. The optimized conditions reduced the consumption of enzymes and
      hydrolysis time to 7.68 FPU/g biomass and 63.88 hr, respectively, and yielded
      51.82 g/L reducing sugars. The Celluclast 1.5 L and Novozyme 188 enzyme ratio
      were varied to maximize the hydrolyzed sugars. The ABE fermentation, using
      substrate from phosphoric acid pretreatment of corncobs, with 10 g/L glucose
      supplementation produced 11.64 g/L of total ABE, which was close to the control
      experiment using synthetic medium. This study showed that corncobs pretreated
      with phosphoric acid could potentially be used as a substrate without using a
      detoxification process. 

PMID- 24678654
TI  - A perspective on the epidemiology of acetaminophen exposure and toxicity in the
      United States.
AB  - Acetaminophen is a commonly-used analgesic in the US and, at doses of more than 4
      g/day, can lead to serious hepatotoxicity. Recent FDA and CMS decisions serve to
      limit and monitor exposure to high-dose acetaminophen. This literature review
      aims to describe the exposure to and consequences of high-dose acetaminophen
      among chronic pain patients in the US. Each year in the US, approximately 6% of
      adults are prescribed acetaminophen doses of more than 4 g/day and 30,000
      patients are hospitalized for acetaminophen toxicity. Up to half of acetaminophen
      overdoses are unintentional, largely related to opioid-acetaminophen combinations
      and attempts to achieve better symptom relief. Liver injury occurs in 17% of
      adults with unintentional acetaminophen overdose. 

PMID- 24678655
TI  - Determinants of health insurance ownership among women in Kenya: evidence from
      the 2008-09 Kenya demographic and health survey.
AB  - BACKGROUND: The Government of Kenya is making plans to implement a social health
      insurance program by transforming the National Hospital Insurance Fund (NHIF)
      into a universal health coverage program. The objective of this study was to
      examine the determinants associated with health insurance ownership among women
      in Kenya. METHODS: Data came from the 2008-09 Kenya Demographic and Health
      Survey, a nationally representative survey. The sample comprised 8,435 women aged
      15-49 years. Descriptive statistics and multivariable logistic regression
      analysis were used to describe the characteristics of the sample and to identify
      factors associated with health insurance ownership. RESULTS: Being employed in
      the formal sector, being married, exposure to the mass media, having secondary
      education or higher, residing in households in the middle or rich wealth index
      categories and residing in a female-headed household were associated with having
      health insurance. However, region of residence was associated with a lower
      likelihood of having insurance coverage. Women residing in Central (OR = 0.4; p <
      0.01) and North Eastern (OR = 0.1; p < 0.5) provinces were less likely to be
      insured compared to their counterparts in Nairobi province. CONCLUSIONS: As the
      Kenyan government transforms the NHIF into a universal health program, it is
      important to implement a program that will increase equity and access to health
      care services among the poor and vulnerable groups.

PMID- 24678656
TI  - Technical challenges of providing record linkage services for research.
AB  - BACKGROUND: Record linkage techniques are widely used to enable health
      researchers to gain event based longitudinal information for entire populations.
      The task of record linkage is increasingly being undertaken by specialised
      linkage units (SLUs). In addition to the complexity of undertaking probabilistic
      record linkage, these units face additional technical challenges in providing
      record linkage 'as a service' for research. The extent of this functionality, and
      approaches to solving these issues, has had little focus in the record linkage
      literature. Few, if any, of the record linkage packages or systems currently used
      by SLUs include the full range of functions required. METHODS: This paper
      identifies and discusses some of the functions that are required or undertaken by
      SLUs in the provision of record linkage services. These include managing routine,
      on-going linkage; storing and handling changing data; handling different linkage
      scenarios; accommodating ever increasing datasets. Automated linkage processes
      are one way of ensuring consistency of results and scalability of service.
      RESULTS: Alternative solutions to some of these challenges are presented. By
      maintaining a full history of links, and storing pairwise information, many of
      the challenges around handling 'open' records, and providing automated managed
      extractions are solved. A number of these solutions were implemented as part of
      the development of the National Linkage System (NLS) by the Centre for Data
      Linkage (part of the Population Health Research Network) in Australia.
      CONCLUSIONS: The demand for, and complexity of, linkage services is growing. This
      presents as a challenge to SLUs as they seek to service the varying needs of
      dozens of research projects annually. Linkage units need to be both flexible and
      scalable to meet this demand. It is hoped the solutions presented here can help
      mitigate these difficulties.

PMID- 24678657
TI  - Preliminary ultrasonication affects the rate of the bacteriorhodopsin bleaching
      and the effectiveness of the reconstitution process in bacterioopsin.
AB  - The formation process of polymer films based on bacteriorhodopsin (BR) analogs
      requests a high amount of BR samples one time only. The common technique for
      apomembrane formation (preparation of bacterioopsin, BO) is not designed to be
      operated with high concentrations and high volumes of BR, so the use of this
      technique results in a low rate of BR bleaching. To accelerate the process of BR
      bleaching preliminary sonication was used. It was used just as preliminary
      sonication before bleaching of BR samples, so also sonication was used before
      reconstitution of resulted BO samples. These modifications of the common
      technique lead to an acceleration of BR bleaching and an increase in
      effectiveness of reconstitution of BO in comparison with the nonmodified
      technique. The quantitative results of sonication's effect on the bleaching
      acceleration and the effectiveness of reconstitution are different depending on
      the BR strains. 

PMID- 24678658
TI  - Clinical decision making in response to performance validity test failure in a
      psychiatric setting.
AB  - This study examined the clinical utility of a performance validity test (PVT) for
      screening consecutive referrals (N = 436) to a neuropsychology service at a state
      psychiatric hospital treating both civilly committed and forensic patients. We
      created a contingency table with Test of Memory Malingering (TOMM) pass/fail
      (355/81) and secondary gain present/absent (181/255) to examine pass rates
      associated with patient demographic, clinical and forensic status
      characteristics. Of the 81 failed PVTs, 48 had secondary gain defined as active
      criminal legal charges; 33 failed PVTs with no secondary gain. These individuals
      tended to be older, female, Caucasian, and civilly committed compared with the
      group with secondary gain who failed. From estimations of TOMM False Positive
      Rate and True Positive Rate we estimated base rates of neurocognitive malingering
      for our clinical population using the Test Validation Summary (TVS; Frederick &
      Bowden, 2009 ). Although PVT failure is clearly more common in a group with
      secondary gain (31%), there were a number of false positives (11%). Clinical
      ratings of patients without gain who failed suggested cognitive deficits,
      behavioral issues, and inattention. Low scores on PVTs in the absence of
      secondary gain provide useful information on test engagement and can inform
      clinical decisions about testing. 

PMID- 24678660
TI  - Vertically aligned carbon nanotube-sheathed carbon fibers as pristine
      microelectrodes for selective monitoring of ascorbate in vivo.
AB  - Using as-synthesized vertically aligned carbon nanotube-sheathed carbon fibers
      (VACNT-CFs) as microelectrodes without any postsynthesis functionalization, we
      have developed in this study a new method for in vivo monitoring of ascorbate
      with high selectivity and reproducibility. The VACNT-CFs are formed via pyrolysis
      of iron phthalocyanine (FePc) on the carbon fiber support. After electrochemical
      pretreatment in 1.0 M NaOH solution, the pristine VACNT-CF microelectrodes
      exhibit typical microelectrode behavior with fast electron transfer kinetics for
      electrochemical oxidation of ascorbate and are useful for selective ascorbate
      monitoring even with other electroactive species (e.g., dopamine, uric acid, and
      5-hydroxytryptamine) coexisting in rat brain. Pristine VACNT-CFs are further
      demonstrated to be a reliable and stable microelectrode for in vivo recording of
      the dynamic increase of ascorbate evoked by intracerebral infusion of glutamate.
      Use of a pristine VACNT-CF microelectrode can effectively avoid any manual
      electrode modification and is free from person-to-person and/or electrode-to
      electrode deviations intrinsically associated with conventional CF electrode
      fabrication, which often involves electrode surface modification with randomly
      distributed CNTs or other pretreatments, and hence allows easy fabrication of
      highly selective, reproducible, and stable microelectrodes even by
      nonelectrochemists. Thus, this study offers a new and reliable platform for in
      vivo monitoring of neurochemicals (e.g., ascorbate) to largely facilitate future
      studies on the neurochemical processes involved in various physiological events. 

PMID- 24678659
TI  - In vivo imaging reveals sigmoidal growth kinetic of beta-amyloid plaques.
AB  - A major neuropathological hallmark of Alzheimer's disease is the deposition of
      amyloid plaques in the brains of affected individuals. Amyloid plaques mainly
      consist of fibrillar beta-amyloid, which is a cleavage product of the amyloid
      precursor protein. The amyloid-cascade-hypothesis postulates Abeta accumulation
      as the central event in initiating a toxic cascade leading to Alzheimer's disease
      pathology and, ultimately, loss of cognitive function. We studied the kinetics of
      beta-amyloid deposition in Tg2576 mice, which overexpress human amyloid precursor
      protein with the Swedish mutation. Utilizing long-term two-photon imaging we were
      able to observe the entire kinetics of plaque growth in vivo. Essentially, we
      observed that plaque growth follows a sigmoid-shaped curve comprising a cubic
      growth phase, followed by saturation. In contrast, plaque density kinetics
      exhibited an asymptotic progression. Taking into account the fact that a critical
      concentration of Abeta is required to seed new plaques, we can propose the
      following kinetic model of beta-amyloid deposition in vivo. In the early cubic
      phase, plaque growth is not limited by Abeta concentration and plaque density
      increases very fast. During the transition phase, plaque density stabilizes
      whereas plaque volume increases strongly reflecting a robust growth of the
      plaques. In the late asymptotic phase, Abeta peptide production becomes rate
      limiting for plaque growth. In conclusion, the present study offers a direct link
      between in vitro and in vivo studies facilitating the translation of Abeta
      lowering strategies from laboratory models to patients. 

PMID- 24678661
TI  - A novel method for designing and fabricating low-cost facepiece prototypes.
AB  - In 2010, the National Institute for Occupational Safety and Health (NIOSH)
      published new digital head form models based on their recently updated fit-test
      panel. The new panel, based on the 2000 census to better represent the modern
      work force, created two additional sizes: Short/Wide and Long/Narrow. While
      collecting the anthropometric data that comprised the panel, additional three
      dimensional data were collected on a subset of the subjects. Within each sizing
      category, five individuals' three-dimensional data were used to create the new
      head form models. While NIOSH has recommended a switch to a five-size system for
      designing respirators, little has been done in assessing the potential benefits
      of this change. With commercially available elastomeric facepieces available in
      only three or four size systems, it was necessary to develop the facepieces to
      enable testing. This study aims to develop a method for designing and fabricating
      elastomeric facepieces tailored to the new head form designs for use in fit
      testing studies. This novel method used computed tomography of a solid silicone
      facepiece and a number of computer-aided design programs (VolView, ParaView,
      MEGG3D, and RapidForm XOR) to develop a facepiece model to accommodate the
      Short/Wide head form. The generated model was given a physical form by means of
      three-dimensional printing using stereolithography (SLA). The printed model was
      then used to create a silicone mold from which elastomeric prototypes can be
      cast. The prototype facepieces were cast in two types of silicone for use in
      future fit-testing. 

PMID- 24678662
TI  - Investigating a hyper-endemic focus of Taenia solium in northern Lao PDR.
AB  - BACKGROUND: The Taenia solium cysticercosis-taeniasis complex is a Neglected
      Tropical Disease of significant public health importance in many impoverished
      communities worldwide. The parasite is suspected to be endemic in Lao PDR as a
      result of widespread risk factors including open human defecation, free ranging
      pigs and weak systems for meat inspection and carcass condemnation. Reported
      prevalences of human taeniasis throughout the country have ranged from 0-14%,
      although few of these have definitively diagnosed T. solium, grossly
      indistinguishable from Taenia saginata (beef tapeworm) and Taenia asiatica. This
      short communication details the suspicion of a hyper endemic "hotspot" of T.
      solium in a remote Tai Dam village in northern Lao PDR. FINDINGS: Initial
      antibody serosurveillance of four provinces in Lao PDR in 2011 indicated human
      taeniasis and cysticercosis prevalences of 46.7% and 66.7% respectively, in the
      village of Om Phalong in the north of the country. Subsequent copro-antigen ELISA
      on 92 human faecal samples from this same village, representing a total 27.9% of
      the target community, indicated a taeniasis prevalence of 26.1% (95% CI?=?18.2
      35.9). Subsequent PCR and sequencing of samples (n?=?5) all identified as T.
      solium; the other human tapeworms T. saginata and T. asiatica were not detected
      in any of the samples genotyped. CONCLUSION: This is potentially one of the
      highest documented prevalences of T. solium taeniasis to date in Lao PDR, if not
      the Southeast Asia region. This result raises suspicion that other "hotspots" of
      T. solium hyper endemicity may exist in the region, particularly in communities
      where the consumption of raw pork is commonplace as a result of cultural
      practices.

PMID- 24678663
TI  - Evolutionary origin of gastrulation: insights from sponge development.
AB  - BACKGROUND: The evolutionary origin of gastrulation--defined as a morphogenetic
      event that leads to the establishment of germ layers--remains a vexing question.
      Central to this debate is the evolutionary relationship between the cell layers
      of sponges (poriferans) and eumetazoan germ layers. Despite considerable
      attention, it remains unclear whether sponge cell layers undergo progressive fate
      determination akin to eumetazoan primary germ layer formation during
      gastrulation. RESULTS: Here we show by cell-labelling experiments in the
      demosponge Amphimedon queenslandica that the cell layers established during
      embryogenesis have no relationship to the cell layers of the juvenile. In
      addition, juvenile epithelial cells can transdifferentiate into a range of cell
      types and move between cell layers. Despite the apparent lack of cell layer and
      fate determination and stability in this sponge, the transcription factor GATA, a
      highly conserved eumetazoan endomesodermal marker, is expressed consistently in
      the inner layer of A. queenslandica larvae and juveniles. CONCLUSIONS: Our
      results are compatible with sponge cell layers not undergoing progressive fate
      determination and thus not being homologous to eumetazoan germ layers.
      Nonetheless, the expression of GATA in the sponge inner cell layer suggests a
      shared ancestry with the eumetazoan endomesoderm, and that the ancestral role of
      GATA in specifying internalised cells may antedate the origin of germ layers.
      Together, these results support germ layers and gastrulation evolving early in
      eumetazoan evolution from pre-existing developmental programs used for the simple
      patterning of cells in the first multicellular animals.

PMID- 24678665
TI  - Isoflavone Augmentation in Soybean Cell Cultures Is Optimized Using Response
      Surface Methodology.
AB  - Glycine max contains potential therapeutic isoflavones, and its productivity in
      plants is considerably influenced worldwide by several biotic and abiotic
      factors. Optimization of soybean cell suspension cultures (Indian variety, JS
      335) to maximize the cell growth and isoflavone production in the present study
      was performed using response surface methodology (RSM) with three independent
      variables of plant growth regulators, 2,4-dichlorophenoxyacetic acid (2,4-D), 1
      naphthalene acetic acid (alpha-NAA), and kinetin (Kn). The maximum biomass
      achieved was 70.62 g/L dry weight (dw) using the optimized medium of 2.10 mg/L
      2,4-D, 5.52 mg/L alpha-NAA, and 0.35 mg/L Kn supplemented in the Murashige and
      Skoog (MS) basal medium. The total isoflavone content of 38.59 mg/g of dw was
      obtained in the medium with optimized conditions of 1.33 mg/L 2,4-D, 1.76 mg/L
      alpha-NAA, and 0.15 mg/L Kn. In comparison to field-grown soybean seeds, the cell
      suspension cultures profoundly augmented isoflavone concentrations. The optimized
      conditions for both biomass and total isoflavone content were evaluated by
      superimposing the contour plots. The results suggested that the optimized medium
      of cell suspension cultures possibly be used for scale-up studies in bioreactors
      to offer a high content of bioactive isoflavones.

PMID- 24678664
TI  - Compression fracture in the middle of a chronic instrumented fusion that
      developed into pseudarthrosis after balloon kyphoplasty.
AB  - There are only 2 documented cases of vertebral compression fractures occurring
      within a solid lumbar fusion mass: one within the fusion mass after hardware
      removal and the other within the levels of the existing instrumentation 1 year
      postoperatively. The authors report a case of fracture occurring in a chronic (>
      30 years) solid instrumented fusion mass in a patient who underwent kyphoplasty.
      The pain did not improve after the kyphoplasty procedure, and the patient
      developed a posterior cleft in the fusion mass postoperatively. The patient, a 46
      year-old woman, had undergone a T4-L4 instrumented fusion with placement of a
      Harrington rod when she was 12 years old. Adjacent-segment breakdown developed,
      and her fusion was extended to the pelvis, with pedicle screws placed up to L-3
      to capture the existing fusion mass. Almost 2 years after fusion extension, she
      fell down the stairs and suffered an L-2 compression fracture, which is when
      kyphoplasty was performed without pain relief, and she then developed a cleft in
      the posterior fusion mass that was previously intact. She refused further
      surgical options. This case report is meant to alert surgeons of this possibility
      and allow them to consider the rare occurrence of fracture within the fusion mass
      when planning extension of chronic spinal fusions. 

PMID- 24678666
TI  - A review of methods available to estimate solvent-accessible surface areas of
      soluble proteins in the folded and unfolded states.
AB  - Solvent accessible surface area (SASA) of proteins has always been considered as
      a decisive factor in protein folding and stability studies. It is defined as the
      surface characterized around a protein by a hypothetical centre of a solvent
      sphere with the van der Waals contact surface of the molecule. Based on SASA
      values, amino acid residues of a protein can be classified as buried or exposed.
      There are various types of SASAs starting from relative solvent accessibility to
      absolute surface areas. Direct estimation of accurate SASAs of folded proteins
      experimentally at the atomic level is not possible. However, the SASA of a native
      protein can be estimated computationally from the atomic coordinates. Similarly,
      various simulation methods are available to compute the SASA of a protein in its
      unfolded state. In efforts to estimate the changes in SASA related to the protein
      folding, a number of the unfolded state models have been proposed. In this
      review, we have summarized different algorithms and computational tools for SASA
      estimations. Furthermore, online resources for SASA calculations and
      representations have also been discussed in detail. This review will be useful
      for protein chemists and biologists for the accurate measurements of SASA and its
      subsequent applications for the calculation of various biophysical and
      thermodynamic properties of proteins. 

PMID- 24678667
TI  - The end of the line: can ferredoxin and ferredoxin NADP(H) oxidoreductase
      determine the fate of photosynthetic electrons?
AB  - At the end of the linear photosynthetic electron transfer (PET) chain, the small
      soluble protein ferredoxin (Fd) transfers electrons to Fd:NADP(H) oxidoreductase
      (FNR), which can then reduce NADP+ to support C assimilation. In addition to this
      linear electron flow (LEF), Fd is also thought to mediate electron flow back to
      the membrane complexes by different cyclic electron flow (CEF) pathways: either
      antimycin A sensitive, NAD(P)H complex dependent, or through FNR located at the
      cytochrome b6f complex. Both Fd and FNR are present in higher plant genomes as
      multiple gene copies, and it is now known that specific Fd iso-proteins can
      promote CEF. In addition, FNR iso-proteins vary in their ability to dynamically
      interact with thylakoid membrane complexes, and it has been suggested that this
      may also play a role in CEF. We will highlight work on the different Fd
      isoproteins and FNR-membrane association found in the bundle sheath (BSC) and
      mesophyll (MC) cell chloroplasts of the C4 plant maize. These two cell types
      perform predominantly CEF and LEF, and the properties and activities of Fd and
      FNR in the BSC and MC are therefore specialized for CEF and LEF respectively. A
      diversity of Fd isoproteins and dynamic FNR location has also been recorded in C3
      plants, algae and cyanobacteria. This indicates that the principles learned from
      the extreme electron transport situations in the BSC and MC of maize might be
      usefully applied to understanding the dynamic transition between these states in
      other systems.

PMID- 24678668
TI  - The unique photophysical properties of the Peridinin-Chlorophyll-alpha-Protein.
AB  - Peridinin-Chlorophyll-alpha-Proteins (PCPs) are water-soluble light harvesting
      complexes from dinoflagellates. They have unique light-harvesting and energy
      transfer properties which have been studied in details in the last 15 years. This
      review aims to give an overview on all the main aspects of PCPs photophysics,
      with an emphasis on some aspects which have not been reviewed in details so far,
      such as vibrational spectroscopy studies, theoretical calculations, and magnetic
      resonance studies. A paragraph on the present development of PCPs towards
      technological applications is also included. 

PMID- 24678669
TI  - Light harvesting proteins for solar fuel generation in bioengineered
      photoelectrochemical cells.
AB  - The sun is the primary energy source of our planet and potentially can supply all
      societies with more than just their basic energy needs. Demand of electric energy
      can be satisfied with photovoltaics, however the global demand for fuels is even
      higher. The direct way to produce the solar fuel hydrogen is by water splitting
      in photoelectrochemical (PEC) cells, an artificial mimic of photosynthesis. There
      is currently strong resurging interest for solar fuels produced by PEC cells, but
      some fundamental technological problems need to be solved to make PEC water
      splitting an economic, competitive alternative. One of the problems is to provide
      a low cost, high performing water oxidizing and oxygen evolving photoanode in an
      environmentally benign setting. Hematite, alpha-Fe2O3, satisfies many
      requirements for a good PEC photoanode, but its efficiency is insufficient in its
      pristine form. A promising strategy for enhancing photocurrent density takes
      advantage of photosynthetic proteins. In this paper we give an overview of how
      electrode surfaces in general and hematite photoanodes in particular can be
      functionalized with light harvesting proteins. Specifically, we demonstrate how
      low-cost biomaterials such as cyanobacterial phycocyanin and enzymatically
      produced melanin increase the overall performance of virtually no-cost metal
      oxide photoanodes in a PEC system. The implementation of biomaterials changes the
      overall nature of the photoanode assembly in a way that aggressive alkaline
      electrolytes such as concentrated KOH are not required anymore. Rather, a more
      environmentally benign and pH neutral electrolyte can be used. 

PMID- 24678672
TI  - Controlling photoinduced electron transfer via defects self-organization for
      novel functional macromolecular systems.
AB  - The electrons transfer (ET) from an atom or a molecule, donor (D), to another,
      acceptor (A) is the basis of many fundamental chemical and physical processes.
      The ET mechanism is controlled by spatial arrangements of donor and acceptors:
      it's the particular spatial arrangement and thus the particular distance and the
      orientation between the electron donors and acceptors that controls the
      efficiency in charge separation processes in nature. Here, we stress the
      importance of this concept reviewing how spatial distribution of atomic and
      molecular self-assembly can determine the quality and physical features of ET
      process from biology to material science. In this context, we propose novel lab
      on-chip techniques to be used to control spatial distribution of molecules at
      nanoscale. Synchrotron source brightness jointly to focusing optics fabrication
      allows one nowadays to monitor and visualize structures with sub-micrometric
      spatial resolution. This can give us a new powerful tool to set up sophisticated
      X-ray imaging techniques as well as spectroscopic elemental and chemical mapping
      to investigate the structure-function relationship controlling the spatial
      arrangement of the molecules at nanoscale. Finally, we report intriguing recent
      case studies on the possibility to manipulate and control this spatial
      distribution and material functionality at nanoscale by using X ray illumination.

PMID- 24678671
TI  - Structure/function/dynamics of photosystem II plastoquinone binding sites.
AB  - Photosystem II (PSII) continuously attracts the attention of researchers aiming
      to unravel the riddle of its functioning and efficiency fundamental for all life
      on Earth. Besides, an increasing number of biotechnological applications have
      been envisaged exploiting and mimicking the unique properties of this
      macromolecular pigment-protein complex. The PSII organization and working
      principles have inspired the design of electrochemical water splitting schemes
      and charge separating triads in energy storage systems as well as biochips and
      sensors for environmental, agricultural and industrial screening of toxic
      compounds. An intriguing opportunity is the development of sensor devices,
      exploiting native or manipulated PSII complexes or ad hoc synthesized
      polypeptides mimicking the PSII reaction centre proteins as biosensing elements.
      This review offers a concise overview of the recent improvements in the
      understanding of structure and function of PSII donor side, with focus on the
      interactions of the plastoquinone cofactors with the surrounding environment and
      operational features. Furthermore, studies focused on photosynthetic proteins
      structure/function/dynamics and computational analyses aimed at rational design
      of high-quality bio-recognition elements in biosensor devices are discussed. 

PMID- 24678670
TI  - Regulation of photosynthetic electron transport and photoinhibition.
AB  - Photosynthetic organisms and isolated photosystems are of interest for technical
      applications. In nature, photosynthetic electron transport has to work
      efficiently in contrasting environments such as shade and full sunlight at noon.
      Photosynthetic electron transport is regulated on many levels, starting with the
      energy transfer processes in antenna and ending with how reducing power is
      ultimately partitioned. This review starts by explaining how light energy can be
      dissipated or distributed by the various mechanisms of non-photochemical
      quenching, including thermal dissipation and state transitions, and how these
      processes influence photoinhibition of photosystem II (PSII). Furthermore, we
      will highlight the importance of the various alternative electron transport
      pathways, including the use of oxygen as the terminal electron acceptor and
      cyclic flow around photosystem I (PSI), the latter which seem particularly
      relevant to preventing photoinhibition of photosystem I. The control of
      excitation pressure in combination with the partitioning of reducing power
      influences the light-dependent formation of reactive oxygen species in PSII and
      in PSI, which may be a very important consideration to any artificial
      photosynthetic system or technical device using photosynthetic organisms. 

PMID- 24678673
TI  - Photosynthetic machineries in nano-systems.
AB  - Photosynthetic reaction centres are membrane-spanning proteins, found in several
      classes of autotroph organisms, where a photoinduced charge separation and
      stabilization takes place with a quantum efficiency close to unity. The protein
      remains stable and fully functional also when extracted and purified in
      detergents thereby biotechnological applications are possible, for example,
      assembling it in nano-structures or in optoelectronic systems. Several types of
      bionanocomposite materials have been assembled by using reaction centres and
      different carrier matrices for different purposes in the field of light energy
      conversion (e.g., photovoltaics) or biosensing (e.g., for specific detection of
      pesticides). In this review we will summarize the current status of knowledge,
      the kinds of applications available and the difficulties to be overcome in the
      different applications. We will also show possible research directions for the
      close future in this specific field. 

PMID- 24678675
TI  - 2,4-Diaryl-1,3-chalcogen azoles bearing pentafluorosulfanyl SF5 groups: a
      synthetic and structural study.
AB  - A series of new 2,4-diaryl-1,3-chalcogen azoles having pentafluorosulfanyl SF5
      functional groups has been prepared by means of the two-component cyclization of
      the selenoamide or thioamide with alpha-bromoketones. The selenoamides or
      thioamides were obtained from the reaction of Woollins' reagent or Lawesson's
      reagent with 4-pentafluorosulfanylbenzonitrile, followed by hydrolysis with
      water. All new compounds were characterized by (1)H, (13)C, (77)Se, (19)F NMR
      spectroscopy, and accurate mass measurement. X-ray crystal structure analysis of
      the selenoamide, thioamide, and 2,4-diarylpentafluorosulfanyl-1,3-chalcogen
      azoles reveal that the selenoamide and thioamide have very similar structural
      features along with similar intermolecular interactions such as the pi-pi
      stacking and the weak N-H...E (E = S or Se) hydrogen bonding. The 2,4
      diarylpentafluorosulfanyl-1,3-chalcogen azoles show the newly formed five
      membered N(1)-C(2)-E(3)-C(4)-C(5) ring is either perfectly planar (and coplanar
      with two peripheral aryl ring planes) or near-planar. The pi-pi intermolecular
      interactions and the weak C-H...pi and C-H...X (X = Br, F, O) hydrogen bonding
      are discussed in the cases of 2,4-diarylpentafluorosulfanyl-1,3-chalcogen azoles.

PMID- 24678676
TI  - Hardy personality and burnout syndrome among nursing students in three Brazilian
      universities-an analytic study.
AB  - BACKGROUND: Nursing students may exhibit the characteristics of resistance to
      stress, such as hardiness, which can reduce the risk of burnout. However, we
      found only one published study about these phenomena among nursing students.
      Thus, we investigated the association between hardiness and burnout in such
      students. METHODS: An analytic, cross-sectional study was conducted among 570
      nursing students from three Brazilian universities. Data were collected relating
      to sociodemographic characteristics, hardiness, and burnout, which we analyzed
      using inferential statistics. RESULTS: We observed that 64.04% of nursing
      students in the sample had a high level of emotional exhaustion, 35.79% had a
      high level of cynicism, and 87.72% had a low level of professional efficacy:
      these are dimensions of burnout. We also found that 48.77% had a high level of
      control, 61.40% a high level of commitment, and 35.44% a high level of challenge:
      these are dimensions of hardiness. Only 24.74% of the students experienced
      burnout, and 21.93% met the criteria for a hardy personality. There was a
      statistically significant difference between the frequency of hardiness and
      burnout (p = 0.033), with 68.00% of hardy students not exhibiting burnout.
      CONCLUSIONS: Although nursing students live with educational stressors, burnout
      was not preponderant in our sample students; this may be linked to hardiness.
      Thus, given its benefits to student life and health, we recommend the development
      of strategies to promote hardiness among nursing students.

PMID- 24678677
TI  - The spectrum of cervical glandular neoplasia and issues in differential
      diagnosis.
AB  - CONTEXT: Premalignant and malignant glandular lesions of the cervix are known to
      often cause diagnostic problems with a variety of benign (more common) as well as
      other malignant mimics, the latter setting often being represented by secondary
      involvement by endometrioid endometrial carcinoma especially in small samplings.
      OBJECTIVE: To highlight key histologic features and immunohistochemical markers
      that may be helpful in the distinction of in situ endocervical carcinoma from
      benign glandular proliferations, and those that separate different subtypes of
      invasive endocervical carcinoma, as well as invasive carcinoma from other
      carcinomas secondarily involving the cervix and nonneoplastic proliferations of
      the cervix. CONCLUSIONS: Clinical and morphologic features as well as
      immunohistochemistry results should be used in conjunction in the differential
      diagnosis of glandular proliferations of the cervix, as correct interpretation
      has major clinical consequences for the patient in most instances (especially
      benign versus malignant). Immunohistochemical markers should be used as part of a
      panel of antibodies, as exceptions may occur to the usual pattern of staining,
      and if used singly, they may mislead the pathologist to establish a wrong
      diagnosis.

PMID- 24678678
TI  - Endometrial intraepithelial neoplasia.
AB  - CONTEXT: Developed in conjunction with molecular and progression data, the
      sequence classification schema for endometrial intraepithelial neoplasia
      (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method
      for classification of endometrial biopsies. OBJECTIVE: To review current data
      supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the
      hormone-driven endometrial sequence from anovulation/disordered proliferative
      endometrium through BH and EIN and their diagnostic difficulty. DATA SOURCES: A
      comprehensive review of EIN literature based on literature indexed by PubMed
      (National Library of Medicine) and Google Scholar. CONCLUSIONS: The BH/EIN schema
      is gaining wider acceptance among pathologist and clinicians. The research
      leading to the EIN criteria is based on molecular and progression data. The
      BH/EIN schema has better reproducibility among pathologists, is intuitively easy
      to use, and requires understanding of endometrial physiology and neoplasia.

PMID- 24678679
TI  - Progress toward improved leadership and management training in pathology.
AB  - CONTEXT: Competency gaps in leadership and laboratory management skills continue
      to exist between what training programs deliver and what recent graduates and
      future employers expect. A number of recent surveys substantiate this. Interest
      in delivering content in these areas is challenged by time constraints, the
      presence of knowledgeable faculty role models, and the necessary importance
      placed on diagnostic skills development, which overshadows any priority trainees
      have toward developing these skills. OBJECTIVE: To describe the problem, the near
      future horizon, the current solutions, and the recommendations for improving
      resident training in laboratory management. DATA SOURCES: The demands of new
      health care delivery models and the value being placed on these skills by the
      Pathology Milestones and Next Accreditation System initiative of the
      Accreditation Council for Graduate Medical Education for training programs
      emphasizes their importance. This initiative includes 6 milestone competencies in
      laboratory management. Organizations like the American Society for Clinical
      Pathology, the American Pathology Foundation, the College of American
      Pathologists, and the Association of Pathology Chairs Program Directors Section
      recognize these competencies and are working to create new tools for training
      programs to deploy. CONCLUSIONS: It is our recommendation that (1) every training
      program develop a formal educational strategy for management training, (2)
      greater opportunity and visibility be afforded for peer-reviewed publications on
      management topics in mainstream pathology literature, and (3) pathology
      milestones-oriented tools be developed to assist program directors and their
      trainees in developing this necessary knowledge and skills.

PMID- 24678680
TI  - Progress and potential: training in genomic pathology.
AB  - CONTEXT: Genomic medicine is revolutionizing patient care. Physicians in areas as
      diverse as oncology, obstetrics, and infectious disease have begun using next
      generation sequencing assays as standard diagnostic tools. OBJECTIVE: To review
      the role of pathologists in genomic testing as well as current educational
      programs and future training needs in genomic pathology. DATA SOURCES: Published
      literature as well as personal experience based on committee membership and
      genomic pathology curricular design. CONCLUSIONS: Pathologists, as the directors
      of the clinical laboratories, must be prepared to integrate genomic testing into
      their practice. The pathology community has made significant progress in genomics
      related education. A continued coordinated and proactive effort will ensure a
      future vital role for pathologists in the evolving health care system and also
      the best possible patient care.

PMID- 24678681
TI  - Pathology training in informatics: evolving to meet a growing need.
AB  - CONTEXT: The mechanics of the practice of medicine in general and of pathology in
      particular is evolving rapidly with the rise in the use of electronic information
      systems for managing the care of individual patients, including the ordering and
      reporting of laboratory tests, maintaining the health of served populations, and
      documenting the full range of health care activities. Pathologists currently in
      practice and those in training need to acquire additional skills in informatics
      to be prepared to maintain a central role in patient care. OBJECTIVE: To
      summarize the evolving landscape of pathology informatics, with particular
      attention to the preparation of pathologists for this discipline and to the
      possible influence of the new subspecialty certification in clinical informatics.
      DATA SOURCES: Most of the information discussed is drawn from the authors' direct
      experience with informatics, resident and fellow education, and the organizations
      supporting these activities in pathology. CONCLUSIONS: The increasing reliance of
      medical practice on electronic health records and other clinical information
      systems is creating a greater need for physicians skilled in the use and
      management of these tools. The establishment of clinical informatics as a formal
      subspecialty in medicine will likely help secure a role for physicians within
      information management structures at health care institutions. Pathologists must
      actively engage in informatics to assure that our specialty is appropriately
      recognized and represented in this growing discipline.

PMID- 24678674
TI  - A comparison between plant photosystem I and photosystem II architecture and
      functioning.
AB  - Oxygenic photosynthesis is indispensable both for the development and maintenance
      of life on earth by converting light energy into chemical energy and by producing
      molecular oxygen and consuming carbon dioxide. This latter process has been
      responsible for reducing the CO2 from its very high levels in the primitive
      atmosphere to the present low levels and thus reducing global temperatures to
      levels conducive to the development of life. Photosystem I and photosystem II are
      the two multi-protein complexes that contain the pigments necessary to harvest
      photons and use light energy to catalyse the primary photosynthetic endergonic
      reactions producing high energy compounds. Both photosystems are highly organised
      membrane supercomplexes composed of a core complex, containing the reaction
      centre where electron transport is initiated, and of a peripheral antenna system,
      which is important for light harvesting and photosynthetic activity regulation.
      If on the one hand both the chemical reactions catalysed by the two photosystems
      and their detailed structure are different, on the other hand they share many
      similarities. In this review we discuss and compare various aspects of the
      organisation, functioning and regulation of plant photosystems by comparing them
      for similarities and differences as obtained by structural, biochemical and
      spectroscopic investigations. 

PMID- 24678682
TI  - The American Board of Pathology's Maintenance of Certification program update.
AB  - CONTEXT: The American Board of Pathology (ABP) began issuing time-limited
      certificates in 2006. New diplomates of the ABP are required to participate in
      the ABP's Maintenance of Certification (MOC) program to maintain certification.
      Voluntary participation in the MOC program is also available to diplomates with
      non-time-limited certificates. OBJECTIVE: To update the pathology community on
      the requirements of the ABP's MOC program and some current MOC policies and to
      demonstrate the value of MOC participation for both time-limited and non-time
      limited certificate holders. DATA SOURCES: This review uses ABP-archived minutes
      of the MOC Committee, the ABP MOC Booklet of Information, the ABP Pathway system
      reports, and the collective experiences of the ABP trustees and staff.
      CONCLUSIONS: The ABP's MOC program has active participation by almost 5000
      diplomates of the ABP. The ABP, in conjunction with the American Board of Medical
      Specialties, continually strives to enhance the relevance and value of MOC to our
      diplomates and to the public.

PMID- 24678683
TI  - Selective pathology fellowships: diverse, innovative, and valuable subspecialty
      training.
AB  - CONTEXT: Although selective pathology fellowships have a long-standing history of
      developing trainees with advanced expertise in specific areas of pathology other
      than those of the American Board of Pathology-certified subspecialties, the
      widespread interest in this training continues to grow. OBJECTIVE: To describe
      the historical background and current status of selective pathology fellowships,
      and to provide examples of 3 programs. In addition, Accreditation Council for
      Graduate Medical Education (ACGME)-accredited programs and nonaccredited programs
      in Selective Pathology are compared. DATA SOURCES: ACGME data banks and publicly
      available online materials were used. Program directors of the fellowships
      examples in this paper provided program-specific information. Additionally, an
      online survey of the program directors and program coordinators of ACGME
      accredited programs and nonaccredited programs in selective pathology was
      performed. CONCLUSIONS: There are currently 76 ACGME-accredited selective
      pathology programs. The programs are distributed between 3 major categories:
      surgical pathology, focused anatomic pathology, and focused clinical pathology.
      Although the vast majority of programs are concerned that their funding source
      may be cut in the next 3 years, most programs will not change the number of
      fellowship positions in their programs. Program requirements devoted specifically
      and solely to selective pathology have been developed and are in effect. The
      value of this training is recognized not only by pathologists, but by clinicians
      as well, in both academia and private practice. Importantly, the diversity and
      innovation inherent in selective pathology allow these programs to adeptly
      address new subspecialty areas and technologic advances in the current and
      evolving practice of pathology.

PMID- 24678684
TI  - Fluorescence immunophenotyping and interphase cytogenetics (FICTION) detects BCL6
      abnormalities, including gene amplification, in most cases of nodular lymphocyte
      predominant Hodgkin lymphoma.
AB  - CONTEXT: BCL6 translocations are a frequent finding in B-cell lymphomas of
      diverse subtypes, including some cases of nodular lymphocyte-predominant Hodgkin
      lymphoma (NLPHL). However, reliable analysis of BCL6 rearrangements using
      fluorescence in situ hybridization is difficult in NLPHL because of the relative
      paucity of neoplastic cells. Combined immunofluorescence microscopy and
      fluorescence in situ hybridization, or fluorescence immunophenotyping and
      interphase cytogenetics as a tool for the investigation of neoplasms (FICTION),
      permits targeted analysis of neoplastic cells. OBJECTIVE: To better define the
      spectrum of BCL6 abnormalities in NLPHL using FICTION analysis. DESIGN: We
      performed an optimized FICTION analysis of 24 lymph nodes, including 11 NLPHL, 5
      follicular hyperplasia with prominent progressive transformation of germinal
      centers, and 8 follicular hyperplasia without progressive transformation of
      germinal centers. RESULTS: BCL6 rearrangement was identified in 5 of 11 cases of
      NLPHL (46%). In addition, BCL6 gene amplification, with large clusters of BCL6
      signals in the absence of chromosome 3 aneuploidy, was detected in 3 of 11 cases
      of NLPHL (27%). One NLPHL showed extra copies of BCL6 present in conjunction with
      multiple copies of chromosome 3. Altogether, we detected BCL6 abnormalities in 9
      of 11 cases of NLPHL (82%). None of the progressive transformation of germinal
      centers or follicular hyperplasia cases showed BCL6 abnormalities by FICTION.
      CONCLUSIONS: To our knowledge, this is the first report of BCL6 gene
      amplification in NLPHL. Our optimized protocol for FICTION permits detection of
      cytogenetic abnormalities in most NLPHL cases and may represent a useful
      ancillary diagnostic technique.

PMID- 24678685
TI  - Use of the ADAMTS13 activity assay improved the accuracy and efficiency of the
      diagnosis and treatment of suspected acquired thrombotic thrombocytopenic
      purpura.
AB  - CONTEXT: Acquired thrombotic thrombocytopenic purpura (A-TTP) is a rare but
      significant disease requiring rapid diagnosis and treatment. The diagnosis is
      often difficult because of variability in the presence of specific clinical
      criteria. The primary etiology of A-TTP involves inhibitors directed against
      ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif,
      member 13). Literature has shown that the ADAMTS13 activity assay is sensitive
      and specific for identifying cases of A-TTP, and application of this test as an
      on-site screening method has not been fully explored. OBJECTIVE: Our objective is
      to determine if the ADAMTS13 activity assay can be used as a successful, on-site
      diagnostic modality to rapidly identify cases of A-TTP and prevent unnecessary
      use of prophylactic therapeutic plasma exchange. DESIGN: A retrospective analysis
      was performed including 152 patients with clinically suspected A-TTP, screened
      using the ADAMTS13 activity assay. Results were correlated with potential
      therapeutic plasma exchange treatment for all cases highly suspicious for A-TTP
      and evaluated for unnecessary patient morbidity and financial cost. RESULTS: The
      ADAMTS13 activity assay had an overall sensitivity and specificity of 100% and
      99%, respectively. The positive predictive value was 91% and the negative
      predictive value was 100%. In 95% of the studies ordered, A-TTP was ruled out,
      leading to decreased patient morbidity and $1.7 million of potential treatment
      costs avoided. CONCLUSION: Implementation of the fluorescence energy transfer
      based ADAMTS13 activity assay as a point-of-care laboratory study decreased
      patient morbidity while also directing more efficient employment of therapeutic
      plasma exchange in cases of suspected A-TTP.

PMID- 24678686
TI  - Biopsies of facial dermatoses made simple.
AB  - CONTEXT: Biopsy of the face is rarely done for inflammatory skin diseases, unless
      the entire process is confined to the face. OBJECTIVE: We hypothesized that
      facial dermatitis has a differential diagnosis that is more limited than the
      differential diagnosis of inflammatory skin diseases that affect other parts of
      the body. To our knowledge, the classification of inflammatory skin diseases
      occurring on the face has never been conducted before in the English literature.
      DESIGN: The most-recent 100 facial biopsies of inflammatory skin conditions were
      retrieved from our files, and the cases were categorized into the main
      inflammatory skin patterns. RESULTS: Forty-seven cases (47%) were categorized as
      interface dermatitis, 2 cases (2%) as psoriasiform dermatitis, 11 cases (11%) as
      spongiotic dermatitis, 16 cases (16%) as diffuse and nodular dermatitis, 8 cases
      (8%) as perivascular dermatitis, 14 cases (14%) as folliculitis and
      perifolliculitis, 1 case (1%) as panniculitis, and 1 case (1%) as fibrosing
      dermatitis. The number of diagnostic entities represented within each of these
      patterns was small. CONCLUSIONS: We believe that facial dermatitis should have
      its own more-circumscribed differential diagnosis. From a practical viewpoint,
      many of the inflammatory skin diseases that affect other parts of the body should
      be excluded from the differential diagnosis after the tissue is determined to be
      from a facial skin biopsy, and others should not be considered unless the biopsy
      is from the face.

PMID- 24678687
TI  - Determination of HER2/neu status: a pilot study comparing HER2/neu dual in situ
      hybridization DNA probe cocktail assay performed on cell blocks to
      immunohistochemisty and fluorescence in situ hybridization performed on
      histologic specimens.
AB  - CONTEXT: Validation of new methodologies for determining human epidermal growth
      factor receptor 2 gene (HER2/neu) amplification status is crucial for advancing
      the standard of care and determining treatment for patients with primary and/or
      metastatic breast carcinoma. OBJECTIVE: To compare results of HER2/neu gene
      amplification status by 2-color chromogenic in situ hybridization (ISH) on cell
      block material to HER2/neu status by immunohistochemistry (IHC) and/or
      fluorescence in situ hybridization (FISH) in the corresponding resection specimen
      or previous biopsy specimen. DESIGN: Formalin, thrombin, and Cellient cell blocks
      were prepared from cytologic samples obtained from resection specimens from 27
      patients with invasive breast carcinoma. In situ hybridization was performed on
      cell block sections from 18 of the collected cases, on both the Ventana BenchMark
      ULTRA and the Ventana BenchMark XT, and the HER2/neu gene amplification status
      was determined. This was then compared to the HER2/neu status by IHC and/or FISH
      in the resection specimen or previous biopsy specimen. RESULTS: Comparison of
      HER2/neu status by ISH on the quantifiable cell block sections showed 100%
      correlation with the HER2/neu status determined by IHC or FISH in the
      corresponding histologic specimens. The results from thrombin and formalin cell
      blocks were statistically superior to the results from Cellient cell blocks on
      both Ventana instruments. CONCLUSIONS: While further validation and study are
      needed, preliminary results show that the HER2/neu gene amplification status of
      breast carcinomas can reliably be determined on thrombin and formalin cell block
      material by using ISH. More consistent staining and better signal integrity was
      obtained with the Ventana BenchMark ULTRA than the BenchMark XT.

PMID- 24678688
TI  - Genomic alterations in pulmonary adenocarcinoma in situ in an adolescent patient.
AB  - Lung cancer is a rare event in the pediatric and adolescent population. To date,
      only a few case reports and small case series have been published, and little is
      known about the risk factors associated with this entity in children and
      adolescents. We describe a case of adenocarcinoma in situ in a 15-year-old
      adolescent girl with previous surgical treatment for malignant melanoma. We
      provide a detailed genomic characterization of this neoplasm by comparative
      genomic hybridization, genome-wide single-nucleotide polymorphism array, and
      fluorescence in situ hybridization analyses. We identify chromosomal regions with
      copy number changes and correlate the corresponding genes within these regions
      with the available literature in the area. 

PMID- 24678689
TI  - Blastic plasmacytoid dendritic cell neoplasm: a clinicopathologic review.
AB  - Blastic plasmacytoid dendritic cell neoplasm is a rare entity grouped with the
      acute myeloid leukemia-related precursor neoplasms in the 2008 World Health
      Organization classification. It was previously postulated to originate from
      natural killer cells, T cells, or monocytes but is now believed to arise from the
      plasmacytoid dendritic cell. The pathogenesis of blastic plasmacytoid dendritic
      cell neoplasm is not well understood, although the neoplasm demonstrates frequent
      deletion of tumor suppressor genes, including RB1, CDKN1B, CDKN2A, and TP53.
      Blastic plasmacytoid dendritic cell neoplasm is a clinically aggressive tumor
      that often initially presents as cutaneous lesions and subsequently progresses to
      bone marrow involvement and leukemic dissemination. It is characterized by
      enhanced expression of CD56, CD4, and CD123, which can be detected by flow
      cytometry/immunohistochemistry. The differential diagnoses include myeloid
      sarcoma/acute myeloid leukemia, T-cell lymphoblastic leukemia/lymphoma, NK-cell
      lymphoma/leukemia, and some mature T-cell lymphomas/leukemias. Patients usually
      respond to initial chemotherapy but often relapse. Stem cell transplant may
      improve survival. 

PMID- 24678690
TI  - Four-fold channels are involved in iron diffusion into the inner cavity of plant
      ferritin.
AB  - From an evolutionary point of view, plant and animal ferritins arose from a
      common ancestor, but plant ferritin exhibits different features as compared with
      the animal analogue. One major difference is that the 4-fold channels naturally
      occurring in plant ferritin are hydrophilic, whereas the 4-fold channels in
      animal ferritin are hydrophobic. Prior to this study, however, the function of
      the 4-fold channels in oxidative deposition of iron in phytoferritin remained
      unknown. To elucidate the role of the 4-fold channels in iron oxidative
      deposition in ferritin, three mutants of recombinant soybean seed H-2 ferritin
      (rH-2) were prepared by site-directed mutagenesis, which contained H193A/H197A, a
      4-fold channel mutant, E165I/E167A/E171A, a 3-fold channel mutant, and
      E165I/E167A/E171A/H193A/H197A, where both 3- and 4-channels were mutated. Stopped
      flow, electrode oximetry, and transmission electron microscopy (TEM) results
      showed that H193A/H197A and E165I/E167A/E171A exhibited a similar catalyzing
      activity of iron oxidation with each other, but a pronounced low activity
      compared to rH-2, demonstrating that both the 4-fold and 3-fold hydrophilic
      channels are necessary for iron diffusion in ferritin, followed by oxidation.
      Indeed, among all tested ferritin, the catalyzing activity of
      E165I/E167A/E171A/H193A/H197A was weakest because its 3- and 4- fold channels
      were blocked. These findings advance our understanding of the function of 4-fold
      channels of plant ferritin and the relationship of the structure and function of
      ferritin. 

PMID- 24678691
TI  - Self-reported physical activity and lung function two months after cardiac
      surgery--a prospective cohort study.
AB  - BACKGROUND: Physical activity has well-established positive health-related
      effects. Sedentary behaviour has been associated with postoperative complications
      and mortality after cardiac surgery. Patients undergoing cardiac surgery often
      suffer from impaired lung function postoperatively. The association between
      physical activity and lung function in cardiac surgery patients has not
      previously been reported. METHODS: Patients undergoing cardiac surgery were
      followed up two months postoperatively. Physical activity was assessed on a four
      category scale (sedentary, moderate activity, moderate regular exercise, and
      regular activity and exercise), modified from the Swedish National Institute of
      Public Health's national survey. Formal lung function testing was performed
      preoperatively and two months postoperatively. RESULTS: The sample included 283
      patients (82% male). Two months after surgery, the level of physical activity had
      increased (p < 0.001) in the whole sample. Patients who remained active or
      increased their level of physical activity had significantly better recovery of
      lung function than patients who remained sedentary or had decreased their level
      of activity postoperatively in terms of vital capacity (94 +/- 11% of
      preoperative value vs. 91 +/- 9%; p = 0.03), inspiratory capacity (94 +/- 14% vs.
      88 +/- 19%; p = 0.008), and total lung capacity (96 +/- 11% vs. 90 +/- 11%; p =
      0.01). CONCLUSIONS: An increased level of physical activity, compared to
      preoperative level, was reported as early as two months after surgery. Our data
      shows that there could be a significant association between physical activity and
      recovery of lung function after cardiac surgery. The relationship between
      objectively measured physical activity and postoperative pulmonary recovery needs
      to be further examined to verify these results.

PMID- 24678692
TI  - Modeling the impact of iron-carboxylate photochemistry on radical budget and
      carboxylate degradation in cloud droplets and particles.
AB  - To quantify the effects of an advanced iron photochemistry scheme, the chemical
      aqueous-phase radical mechanism (CAPRAM 3.0i) has been updated with several new
      Fe(III)-carboxylate complex photolysis reactions. Newly introduced ligands are
      malonate, succinate, tartrate, tartronate, pyruvate, and glyoxalate. Model
      simulations show that more than 50% of the total Fe(III) is coordinated by
      oxalate and up to 20% of total Fe(III) is bound in the newly implemented 1:1
      complexes with tartronate, malonate, and pyruvate. Up to 20% of the total Fe(III)
      is found in hydroxo and sulfato complexes. The fraction of [Fe(oxalate)2](-) and
      [Fe(pyruvate)](2+) is significantly higher during nighttime than during daytime,
      which points toward a strong influence of photochemistry on these species.
      Fe(III) complex photolysis is an important additional sink for tartronate,
      pyruvate, and oxalate, with a complex photolysis contribution to overall
      degradation of 46, 40, and 99%, respectively, compared to all possible sink
      reactions with atmospheric aqueous-phase radicals, such as (*)OH, NO3(*), and
      SO4(*) (-). Simulated aerosol particles have a much lower liquid water content
      than cloud droplets, thus leading to high concentrations of species and,
      consequently, an enhancement of the photolysis sink reactions in the aerosol
      particles. The simulations showed that Fe(III) photochemistry should not be
      neglected when considering the fate of carboxylic acids, which constitute a major
      part of aqueous secondary organic aerosol (aqSOA) in tropospheric cloud droplets
      and aqueous particles. Failure to consider this loss pathway has the potential to
      result in a significant overestimate of aqSOA production. 

PMID- 24678693
TI  - Characterization of stem-like cells directly isolated from freshly resected
      laryngeal squamous cell carcinoma specimens.
AB  - Larynx cancer (LCa) is an aggressive malignancy, which is the second most common
      malignant neoplasm of head and neck squamous cell carcinoma. Its incidences have
      been reported to increase and therapeutic options mostly fail to give positive
      clinical response especially for the advanced LCa cases. In this study we aimed
      to isolate stem-like cells from freshly resected LCa tumor specimens and
      characterize them by quantitative real time PCR (qRT-PCR) for expression of
      cancer stem cell markers including SOX2, OCT4, KLF4, ABCG2, CXCR4 and CD44. Our
      results showed that CD133(high) cells directly isolated from freshly resected
      tumor specimens exhibit elevated levels of SOX2, OCT4 and KLF4, and have
      increased expression levels of ABCG2 and CXCR4, which were associated with
      resistance of tumors to regular chemotherapeutic reagents. In conclusion, this
      study offers a useful approach utilizing CD133 to isolate stem cells directly
      from fresh tissues, which gives the opportunity to develop novel therapeutic
      tools specifically targeting these cells through their further characterization. 

PMID- 24678695
TI  - Assessment of the level of agreement in the interpretation of plain radiographs
      of lumbar spondylosis among clinical physiotherapists in Ghana.
AB  - BACKGROUND: Objective physical assessment of patients with lumbar spondylosis
      involves plain film radiographs (PFR) viewing and interpretation by the
      radiologists. Physiotherapists also routinely assess PFR within the scope of
      their practice. However, studies appraising the level of agreement of
      physiotherapists' PFR interpretation with radiologists are not common in Ghana.
      METHOD: Forty-one (41) physiotherapists took part in the cross-sectional survey.
      An assessment guide was developed from findings of the interpretation of three
      PFR of patients with lumbar spondylosis by a radiologist. The three PFR were
      selected from a pool of different radiographs based on clarity, common visible
      pathological features, coverage body segments and short post production period.
      Physiotherapists were required to view the same PFR after which they were
      assessed with the assessment guide according to the number of features identified
      correctly or incorrectly. The score range on the assessment form was 0-24,
      interpreted as follow: 0-8 points (low), 9-16 points (moderate) and 17-24 points
      (high) levels of agreement. Data were analyzed using one sample t-test and
      fisher's exact test at alpha = 0.05. RESULTS: The mean score of interpretation
      for the physiotherapists was 12.7 +/- 2.6 points compared to the radiologist's
      interpretation of 24 points (assessment guide). The physiotherapists' levels were
      found to be significantly associated with their academic qualification (p =
      0.006) and sex (p = 0.001). However, their levels of agreement were not
      significantly associated with their age group (p = 0.098), work settings (p =
      0.171), experience (p = 0.666), preferred PFR view (p = 0.088) and continuing
      education (p = 0.069). CONCLUSIONS: The physiotherapists' skills fall short of
      expectation for interpreting PFR of patients with lumbar spondylosis. The levels
      of agreement with radiologist's interpretation have no link with year of clinial
      practice, age, work settings and continuing education. Thus, routine PFR viewing
      techniques should be made a priority in physiotherapists' continuing professional
      education.

PMID- 24678694
TI  - Cardiovascular function alterations induced by acute paradoxical sleep
      deprivation in rats.
AB  - Sleep loss has been implicated in triggering the hypertension. The goal of the
      present study was investigated the possible mechanisms underlying cardiovascular
      alterations after acute paradoxical sleep deprivation (PSD). Male Wistar rats
      were assigned in two experimental groups: (1) control and (2) PSD for 24 h using
      the modified single platform method. Paradoxical sleep deprived rats exhibited
      higher blood pressure, heart rate (HR) and impaired baroreceptor sensitivity.
      After pharmacological autonomic double blockade (propranolol and methylatropine
      administration), intrinsic heart rate was decreased after PSD. The PSD rats
      showed a reduction in the vagal tone without affecting sympathetic tone.
      Isoproterenol administration (0.001, 0.01 and 1 ug/kg) induced an increase in
      DeltaHR responses in PSD group. Electrocardiographic analysis in response to beta
      adrenergic stimulation indicated that PSD contributed to ventricular cardiac
      arrhythmias. Our findings suggest that acute paradoxical sleep loss induce
      cardiovascular alterations, autonomic imbalance accompanied by impaired
      baroreflex sensitivity and increased arrhythmia susceptibility.

PMID- 24678696
TI  - Characterization, kinetic, and thermodynamic studies of marine pectinase from
      Bacillus subtilis.
AB  - Characterization, kinetic and thermodynamic parameters of purified pectinase from
      Bacillus subtilis, isolated from a marine sediment sample collected from
      Chinchani beach at Tarapore, India, were studied. Marine pectinase produced under
      submerged growth conditions was purified by ammonium sulfate precipitation
      followed by gel filtration chromatography using DEAE cellulose. Partial
      characterization of the marine pectinase was carried out in terms of effect of
      pH, temperature, substrate concentration, and metal ions. It was found that
      pectinase from marine B. subtilis showed maximal activity in alkaline buffer at
      pH 9.0 and at 40 degrees C. It was also found that metal ions, namely, Mn(2+) and
      Fe(2+), stimulate pectinase activity. Marine pectinase followed Michaelis-Menten
      kinetics. The kinetics and thermodynamic parameters of the purified marine
      pectinase from B. subtilis were studied as the characterization of the enzyme is
      vital for its use in industrial processes. 

PMID- 24678697
TI  - Clinical utility of ambulatory blood pressure monitoring in the management of
      hypertension.
AB  - Accurate blood pressure (BP) measurement is essential for the diagnosis,
      monitoring and management of hypertension. However, conventional office-based BP
      readings have several limitations that include a low reproducibility, the white
      coat effect and the existence of masked hypertension. These limitations can be
      addressed through the use of ambulatory BP monitoring. Because ambulatory
      monitoring provides measurements at specific time intervals throughout a 24-hour
      period, this technique represents a better picture of the normal fluctuations in
      BP levels associated with daily activities and sleep. In addition, end-organ
      damage associated with hypertension is more closely related to ambulatory BP than
      office BP measurements and ambulatory BP profile give better prediction of
      clinical outcome than conventional BP measurements. 

PMID- 24678698
TI  - Quantification of structural changes of UHMWPE components in total joint
      replacements.
AB  - BACKGROUND: At present time the number of implantations of joint replacements as
      well as their revisions increases. Higher demands are required on the quality and
      longevity of implants. The aim of this work was to determine the degree of
      oxidative degradation and the amount of free/residual radicals in selected ultra
      high molecular weight polyethylene (UHMWPE) components of the joint replacements
      and demonstrate that the measured values are closely connected with quality and
      lifetime of the polymer components. METHODS: We tested both new (4 samples) and
      explanted (4 samples) UHMWPE polymers for total joint replacements. The samples
      were characterized by infrared spectroscopy (IR), electron spin resonance (ESR)
      and microhardness (MH) test. The IR measurements yielded the values of oxidation
      index and trans-vinylene index. The ESR measurements gave the free radicals
      concentration. RESULTS: In the group of new polyethylene components, we found
      oxidation index values ranging from 0.00-0.03 to 0.24. The trans-vinylene index
      values ranged from 0.044 to 0.080. The value of free radical concentration was
      zero in virgin and also in sample of Beznoska Company and non-zero in the other
      samples. In the group of explanted components, the measured values were
      associated with their history, micromechanical properties and performance in
      vivo. CONCLUSIONS: We demonstrated that measuring of oxidative damage may help
      the orthopaedic surgeon in estimating the quality of UHMWPE replacement component
      and thus radically to avoid early joint replacement failure due to worse
      polyethylene quality.

PMID- 24678699
TI  - Decline in temperature and humidity increases the occurrence of influenza in cold
      climate.
AB  - BACKGROUND: Both temperature and humidity may independently or jointly contribute
      to the risk of influenza infections. We examined the relations between the level
      and decrease of temperature, humidity and the risk of influenza A and B virus
      infections in a subarctic climate. METHODS: We conducted a case-crossover study
      among military conscripts (n = 892) seeking medical attention due to respiratory
      symptoms during their military training period and identified 66 influenza A and
      B cases by PCR or serology. Meteorological data such as measures of average and
      decline in ambient temperature and absolute humidity (AH) during the three
      preceding days of the onset (hazard period) and two reference periods, prior and
      after the onset were obtained. RESULTS: The average temperature preceding the
      influenza onset was -6.8 +/- 5.6 degrees C and AH 3.1 +/- 1.3 g/m3. A decrease in
      both temperature and AH during the hazard period increased the occurrence of
      influenza so that a 1 degrees C decrease in temperature and 0.5 g decrease per m3
      in AH increased the estimated risk by 11% [OR 1.11 (1.03 to 1.20)] and 58% [OR
      1.58 (1.28 to 1.96)], respectively. The occurrence of influenza infections was
      positively associated with both the average temperature [OR 1.10 per 1 degrees C
      (95% confidence interval 1.02 to 1.19)] and AH [OR 1.25 per g/m3 (1.05 to 1.49)]
      during the hazard period prior to onset. CONCLUSION: Our results demonstrate that
      a decrease rather than low temperature and humidity per se during the preceding
      three days increase the risk of influenza episodes in a cold climate.

PMID- 24678700
TI  - Globally visualizing the microtubule-dependent transport behaviors of influenza
      virus in live cells.
AB  - Understanding the microtubule-dependent behaviors of viruses in live cells is
      very meaningful for revealing the mechanisms of virus infection and endocytosis.
      Herein, we used a quantum dots-based single-particle tracking technique to
      dynamically and globally visualize the microtubule-dependent transport behaviors
      of influenza virus in live cells. We found that the intersection configuration of
      microtubules can interfere with the transport behaviors of the virus in live
      cells, which lead to the changing and long-time pausing of the transport behavior
      of viruses. Our results revealed that most of the viruses moved along straight
      microtubules rapidly and unidirectionally from the cell periphery to the
      microtubule organizing center (MTOC) near the bottom of the cell, and the viruses
      were confined in the grid of microtubules near the top of the cell and at the
      MTOC near the bottom of the cell. These results provided deep insights into the
      influence of entire microtubule geometry on the virus infection. 

PMID- 24678702
TI  - Removal of reactive blue 19 from aqueous solution by pomegranate residual-based
      activated carbon: optimization by response surface methodology.
AB  - BACKGROUND: In this research, response surface methodology (RSM) was applied to
      optimize Reactive Blue 19 removal by activated carbon from pomegranate residual.
      A 24 full factorial central composite design (CCD) was applied to evaluate the
      effects of initial pH, adsorbent dose, initial dye concentration, and contact
      time on the dye removal efficiency. METHODOLOGY: The activated carbon prepared by
      50 wt.% phosphoric acid activation under air condition at 500 degrees C. The
      range of pH and initial dye concentration were selected in a way that considered
      a wide range of those variables. Furthermore, the range of contact time and
      adsorbent dose were determined based on initial tests. Levels of selected
      variables and 31 experiments were determined. MiniTab (version 16.1) was used for
      the regression and graphical analyses of the data obtained. RESULTS: It was found
      that the decrease of initial dye concentration and the increase of initial pH,
      adsorbent dose, and contact time are beneficial for improving the dye removal
      efficiency. Analysis of variance (ANOVA) results presented high R2 value of
      99.17% for Reactive Blue 19 dye removal, which indicates the accuracy of the
      polynomial model is acceptable. CONCLUSIONS: Initial pH of 11, adsorbent dose of
      1.025 g/L, initial dye concentration of 100 mg/L, and contact time of 6.8 minutes
      found to be the optimum conditions. Dye removal efficiency of 98.7% was observed
      experimentally at optimum point which confirmed close to model predicted (98.1%)
      result.

PMID- 24678701
TI  - An empirical evaluation of two-stage species tree inference strategies using a
      multilocus dataset from North American pines.
AB  - BACKGROUND: As it becomes increasingly possible to obtain DNA sequences of
      orthologous genes from diverse sets of taxa, species trees are frequently being
      inferred from multilocus data. However, the behavior of many methods for
      performing this inference has remained largely unexplored. Some methods have been
      proven to be consistent given certain evolutionary models, whereas others rely on
      criteria that, although appropriate for many parameter values, have peculiar
      zones of the parameter space in which they fail to converge on the correct
      estimate as data sets increase in size. RESULTS: Here, using North American
      pines, we empirically evaluate the behavior of 24 strategies for species tree
      inference using three alternative outgroups (72 strategies total). The data
      consist of 120 individuals sampled in eight ingroup species from subsection
      Strobus and three outgroup species from subsection Gerardianae, spanning ~47
      kilobases of sequence at 121 loci. Each "strategy" for inferring species trees
      consists of three features: a species tree construction method, a gene tree
      inference method, and a choice of outgroup. We use multivariate analysis
      techniques such as principal components analysis and hierarchical clustering to
      identify tree characteristics that are robustly observed across strategies, as
      well as to identify groups of strategies that produce trees with similar
      features. We find that strategies that construct species trees using only
      topological information cluster together and that strategies that use additional
      non-topological information (e.g., branch lengths) also cluster together.
      Strategies that utilize more than one individual within a species to infer gene
      trees tend to produce estimates of species trees that contain clades present in
      trees estimated by other strategies. Strategies that use the minimize-deep
      coalescences criterion to construct species trees tend to produce species tree
      estimates that contain clades that are not present in trees estimated by the
      Concatenation, RTC, SMRT, STAR, and STEAC methods, and that in general are more
      balanced than those inferred by these other strategies. CONCLUSIONS: When
      constructing a species tree from a multilocus set of sequences, our observations
      provide a basis for interpreting differences in species tree estimates obtained
      via different approaches that have a two-stage structure in common, one step for
      gene tree estimation and a second step for species tree estimation. The methods
      explored here employ a number of distinct features of the data, and our analysis
      suggests that recovery of the same results from multiple methods that tend to
      differ in their patterns of inference can be a valuable tool for obtaining
      reliable estimates.

PMID- 24678704
TI  - Expanding the therapeutic potential of statins by means of nanotechnology enabled
      drug delivery systems.
AB  - Statins are effective lipid lowering agents traditionally used for the primary
      and secondary prevention of cardiovascular disease. Statins also exert a range of
      pleiotropic effects that make them attractive candidates for use in a wide range
      of disorders, in particular inflammatory and immune mediated conditions. However,
      the exploitation of such pleiotropic effects has been greatly hindered by poor
      bioavailability and adverse effects on muscles and the liver at higher doses.
      Nanotechnology is often suggested as the solution to this problem, as it enables
      an increased bioavailability of statins. Moreover, colloidal carriers can offer
      targeted drug delivery approaches that enable localised biological effects of
      statins, further reducing their potential for unwanted toxicity and adverse
      effects. This article reviews the available evidences for the increased potential
      of statin therapy when administered in nano-formulations such as nanocrystals,
      nanoparticles, liposomes, micelles and various nano-enabled devices. 

PMID- 24678703
TI  - Liposomes as nanovaccine delivery systems.
AB  - Since the discovery of liposomes by Alec Bangham in mid-1960s, these phospholipid
      vesicles have been widely used as pharmaceutical carriers. Liposomes have been
      extensively studied in the vaccine delivery field as a carrier and an immune
      stimulating agent. Liposomes are usually formulated as nanoparticles, mimicking
      the properties of pathogens, and have the ability to induce humoral and cell
      mediated immune responses. In this review, we focused on modern nanotechnology
      based approaches for the improvement of liposomal vaccine delivery systems.
      Topics such as size-dependent uptake, processing and activation of antigen
      presenting cells, targeting liposomes and route of administration are discussed.

PMID- 24678705
TI  - Optimisation of synthetic vector systems for cancer gene therapy - the role of
      the excess of cationic dendrimer under physiological conditions.
AB  - We have previously demonstrated in a therapeutic study that a single systemic
      course of DAB-Am16 dendriplexes loaded with plasmid expressing TNFalpha over a
      period of time of 10 days led to a regression of 100% of tumours and to long term
      cures of up to 80% of animals. However, the formulation had a relatively low
      colloidal stability requiring administration soon after nanoparticle preparation.
      Similar to other cationic polyplex and dendrimer DNA delivery systems, DAB-AM16
      dendrimer formulations contained a substantial proportion of free polymer; this
      free polymer is present independently of the specific polymer:DNA ratio and
      increases with increasing proportion of polymer (N:P charge ratio) in the
      formulation. It has previously been shown for this and other systems that the
      excess of polymer plays a role in promoting the transfection efficiency of
      synthetic vectors. This has been linked to effects of the polymer on the
      efficiency of intracellular processing, e.g. endosomal release. However, the free
      polymer may have additional effects that are relevant to the efficiency of the
      formulation. This study therefore considered the effect of free dendrimer on the
      colloidal stability of the complexes, the interaction of the complex with the
      formulation medium, and with biological components, i.e. electrolytes and serum
      proteins after administration. Analysis of the total potential of interaction
      shows that, even at high N:P ratios, the excess of free dendrimer in the medium
      is not enough to induce the aggregation of the formulation due to depletion
      forces. This finding is unusual and can be attributed to the particularly low Mw
      of these dendrimers (1.6 kDa). On the other hand, formulations are highly
      sensitive to the strength of the dendrimer:DNA interactions. These can be
      controlled by the degree of protonation (alpha) of the dendrimer which is
      strongly dependent on bulk pH. Modulation of the protonation level to alpha>=0.4
      allows reproducible production of colloidally stable particles. Finally, we have
      demonstrated that electrolytes and proteins present in physiological media play a
      crucial role to favour the efficiency of these synthetic vectors reducing the
      toxicity associated with their cationic groups. 

PMID- 24678706
TI  - Adsorption of antisense oligonucleotides targeting malarial topoisomerase II on
      cationic nanoemulsions optimized by a full factorial design.
AB  - Cationic nanoemulsions have been recently considered as potential delivery
      systems for oligonucleotides (ON) targeting Plasmodium falciparum topoisomerase
      II gene. This study is aiming to select the best composition of nanoemulsions
      intended to ON adsorption by means of a 2(3) full factorial design. Based on
      their physicochemical properties, two formulations were selected for further
      studies, both composed by medium chain triglycerides, egg-lecithin, and either
      oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Adsorption
      isotherms of phosphodiester or phosphorothioate ON on the optimized nanoemulsions
      were obtained (ultrafiltration/centrifugation procedure). They showed a
      significant higher amount of ON adsorbed on DOTAP nanoemulsion when compared to
      the OA ones. The Langmuir adsorption model provides the most satisfactory
      representation of the adsorption data. Evidence of ON adsorption could be
      detected by the inversion of the zeta-potential and the morphology of the oil
      droplets examined by transmission electron microscopy. Preliminary results
      regarding hemolytic effect and P. falciparum survival after exposure to optimized
      formulations were related to their physicochemical properties and in vitro
      effects. The overall results showed the potential of the optimized nanoemulsions
      as non-viral carriers for antisense ON against malaria parasites. 

PMID- 24678707
TI  - Recent advances in delivery through the blood-brain barrier.
AB  - Current routes of delivering therapeutics to the brain to treat a variety of
      neurologic conditions include intracerebral, intrathecal, and intranasal
      delivery. Though successes have been achieved through the use of these methods,
      each has limitations that warrant a more universal delivery system involving the
      intravenous pathway. Two main barriers to intravenous delivery are the blood
      brain barrier (BBB) and the blood-cerebrospinal fluid barrier. This review
      discusses potential methods for overcoming barriers of intravenous-mediated brain
      targeting as well as highlights aspects of the highly restrictive BBB anatomy
      that are important to consider in the design of successful drug delivery systems.
      Recent advances in intravenous delivery to the brain have exploited receptor
      mediated transcytosis and BBB disruption, as well as control of carrier
      properties. Currently, three predominant synthetic carriers are being studied to
      transport therapeutics across the BBB: liposomes, metallic nanoparticles, and
      polymersomes. This article also focuses on receptors that may be upregulated by
      brain endothelial cells and their ability to significantly increase brain tissue
      drug distribution when specific targeting moieties to these receptors are
      attached to synthetic nanocarriers. 

PMID- 24678709
TI  - In vitro intestinal co-culture cell model to evaluate intestinal absorption of
      edelfosine lipid nanoparticles.
AB  - Nanotechnology is providing a new therapeutic paradigm by enhancing drug efficacy
      and preventing side-effects. Edelfosine is a synthetic ether lipid analogue of
      platelet activating factor with high antitumor activity. The encapsulation of
      this potent antitumor drug in lipid nanoparticles increases its oral
      bioavailability; moreover, it prevents the hemolytic and gastrointestinal side
      effects of the free drug. The literature points towards lymphatic absorption of
      lipid nanoparticles after oral administration, and previous in vitro and in vivo
      studies stress the protection against toxicity that these nanosystems provide.
      The present study is intended to assess the permeability of lipid nanoparticles
      across the intestinal barrier. Caco-2 monoculture and Caco-2/Raji co-culture were
      used as in vitro models of enterocytes and Microfold cells respectively. Results
      showed that free drug is internalized and possibly metabolized in enterocytes.
      These results do not correlate with those observed in vivo when edelfosine-lipid
      nanoparticles were administered orally in mice, which suggests that the microfold
      model is not a good model to study the absorption of edelfosine-lipid
      nanoparticles across the intestinal barrier in vitro.

PMID- 24678708
TI  - Nanocarriers for respiratory diseases treatment: recent advances and current
      challenges.
AB  - Pulmonary delivery of locally-acting drugs encapsulated in nanocarriers provides
      several advantages for the treatment of respiratory diseases such as asthma,
      chronic obstructive pulmonary diseases, cystic fibrosis, tuberculosis and lung
      cancer. These advantages include, among others, sustained drug delivery to the
      lungs, reduced therapeutic dose and improved patient compliance. The aim of this
      review is to give an updated overview on recent advances recorded in the last few
      years in this field as well as on the major challenges still existing and that
      remain to be overcome before any clinical application. After an outline on the
      cellular and extracellular barriers affecting drug delivery to the airways both
      in physiological and pathological conditions, the significant developments
      recorded using inhaled polymeric- and lipid-based nanocarriers for drug and gene
      delivery to the lung are presented. In this discussion, the major challenges
      existing in the field are evidenced including the understanding of the factors
      governing the mucus penetration capability of these nanocarriers and the
      identification of new technologies for delivering drugs to specific regions or
      cell types of the lungs. In this regard, the recognition of receptor expressed
      only at lung level may facilitate drug targeting to this organ and it should
      improve the therapeutic efficacy of nanocarrier-based treatments for respiratory
      diseases. 

PMID- 24678710
TI  - PEGylated lipid nanocapsules with improved drug encapsulation and controlled
      release properties.
AB  - Drugs with poor lipid and water solubility are some of the most challenging to
      formulate in nanocarriers, typically resulting in low encapsulation efficiencies
      and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for
      their amenability to diverse modifications that allow the formation of domains
      with different physicochemical properties, an interesting feature to address a
      drug encapsulation problem. We explored this problem by encapsulating in PEG-NC
      the promising anticancer drug candidate F10320GD1, used herein as a model for
      compounds with such characteristics. The nanocarriers were prepared from
      Miglyol((r)), lecithin and PEG-sterate through a solvent displacement technique.
      The resulting system was a homogeneous suspension of particles with size around
      200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were
      prepared using water as continuous phase; but we were able to improve this value
      to 85% by fixing the pH of the continuous phase to 9. Interestingly, this
      modification also improved the controlled release properties and the chemical
      stability of the formulation during storage. These differences in pharmaceutical
      properties together with physicochemical data suggest that the pH of the
      continuous phase used for PEG-NC preparation can modify drug allocation, from the
      external shell towards the inner lipid core of the nanocapsules. Finally, we
      tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and
      also in endothelial cells. The results indicated that drug encapsulation led to
      an improvement on drug cytotoxicity in tumor cells, but not in non-tumor
      endothelial cells. Altogether, the data confirms that PEG-NC show adequate
      delivery properties for F10320GD1, and underlines its possible utility as an
      anticancer therapy. 

PMID- 24678711
TI  - PEGylated polyester-based nanoncologicals.
AB  - Several PEGylated polyester-based nanoncologicals have been proposed in the
      literature, some of them nowadays being under preclinical/clinical trials or
      marketed. In this review, we describe the main features of PEGylated polyesters
      and their correspondent nanocarriers. A first part is devoted to intravenously
      injectable PEGylated nanocarriers, which represent the systems most investigated
      so far. After describing fundamental design rules dictated by the administration
      route, PEGylated nanocarriers currently under preclinical/clinical investigation
      or in the market will be described from a technological point of view and related
      therapeutic implications discussed. Finally, new perspective of use of PEGylated
      nanocarriers for oral and pulmonary delivery of anticancer drugs will be
      considered. 

PMID- 24678712
TI  - Nanocarriers & drug delivery: rational design and applications.

PMID- 24678713
TI  - Reliability and validity of the German language version of Girls' Disinclination
      for Physical Activity Scale.
AB  - The high prevalence of insufficient physical activity (PA) among adolescents is
      an important public health issue. Studying reasons for disliking PA might help
      researchers better understand its underlying mechanisms, yet this psychological
      construct has been understudied. This study established the psychometric
      properties of the German language version of the Girls' Disinclination for
      Physical Activity Scale (G-DAS-Ger). Data were collected on a sample of 257
      adolescent girls in Austria (mean age: 13.0 +/- 0.7 years) using the G-DAS-Ger
      and the Physical Activity Enjoyment Scale. One week after the first assessment,
      the questionnaires were re-administered to 78 girls. Between two administrations,
      PA of 215 girls was monitored for seven consecutive days using the ActiGraph
      GT3X+ accelerometers. Confirmatory factor analysis of G-DAS-Ger showed good fit
      for a three-factor model (chi(2)/df = 2.025; Bollen-Stine (B-S) p = 0.159; root
      mean square error of approximation = 0.063; standardised root mean square
      residual = 0.054; comparative fit index = 0.950). Cronbach's alphas for G-DAS-Ger
      factors/subscales ranged 0.64-0.76. The test-retest reliability assessed by
      Spearman's rank correlation ranged 0.62-0.75. Only one subscale correlated
      significantly with vigorous-intensity PA (Spearman's rho = -0.16) and none with
      moderate-to-vigorous-intensity PA, which indicated poor predictive validity of
      the G-DAS-Ger. Correlations between G-DAS-Ger subscales and enjoyment of PA
      ranged from -0.29 to -0.41, indicating satisfactory convergent validity. The G
      DAS-Ger may be used in its present form to assess disinclination for PA among
      adolescent girls in German-speaking countries. However, our results put into
      question the stability of the originally proposed factor structure of the
      questionnaire and its predictive validity among German-speaking adolescent girls.
      Methodological refinements to the G-DAS-Ger may be required to improve its
      psychometric properties in this population.

PMID- 24678714
TI  - Evidence-based medicinal value of Rudbeckia hirta L. flowers.
AB  - A phytochemical investigation on the 5-lipoxygenase (5-LOX) inhibitory methanolic
      extract of Rudbeckia hirta L. flowers yielded 10 phenolic metabolites, including
      three phenolic acids, two phenolic acid esters, four flavonol glycosides and a
      trimethylated flavonol. The structures of the isolated metabolites were
      determined on the basis of spectroscopic analyses and by comparison with the
      literature data. Seven of these metabolites were isolated for the first time from
      the genus Rudbeckia. The in vitro 5-LOX inhibitory, immunomodulatory and
      antioxidant (oxygen radical absorbance capacity) activities of the isolated
      compounds were evaluated, and the results provided a new scientific evidence for
      the ethnopharmacological use of the herb in inflammatory conditions. 

PMID- 24678715
TI  - Hand function in the play behavior of children with cerebral palsy.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of hand function
      on the occupational performance of playing for children with cerebral palsy.
      METHODS: Twenty children with cerebral palsy took part in the study, of both
      genders, aged 3-10 years, with motor abilities ranging from I to V and manual
      abilities from II to IV. Data were collected using the Assessment of Ludic
      Behaviour before and after botulinum toxin was applied in the upper limbs to
      reduce spasticity. RESULTS: Significant differences were found between the scores
      before and after the application of botulinum toxin in relation to the total
      Assessment of Ludic Behaviour score (p < 0.001), as well as in basic ludic
      interest (p = 0.003), basic ludic ability (p < 0.001), ludic attitude (p =
      0.008), and communication of needs and feelings (p = 0.025), except for general
      level of interest (p = 0.957). CONCLUSIONS: The reduction of spasticity permits
      better handling of the play materials, which promotes the children's involvement
      in play situations.

PMID- 24678717
TI  - The importance of sphingolipids and reactive oxygen species in cardiovascular
      development.
AB  - The heart is the first organ in the embryo to form. Its structural and functional
      complexity is the result of a thorough developmental program, where sphingolipids
      play an important role in cardiogenesis, heart maturation, angiogenesis, the
      regulation of vascular tone and vessel permeability. Sphingolipids are necessary
      for signal transduction and membrane microdomain formation. In addition, recent
      evidence suggests that sphingolipid metabolism is directly interconnected to the
      modulation of oxidative stress. However, cardiovascular development is highly
      sensitive to excessive reactive species production, and disturbances in
      sphingolipid metabolism can lead to abnormal development and cardiac disease.
      Therefore, in this review, we address the molecular link between sphingolipids
      and oxidative stress, connecting these pathways to cardiovascular development and
      cardiovascular disease. 

PMID- 24678716
TI  - Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate
      cancer incidence and mortality: a systematic review and meta-analysis.
AB  - BACKGROUND: It has been postulated that non-steroidal anti-inflammatory drugs
      (NSAIDs) use leads to decreased prostate cancer (PCa) risk. In recent years,
      NSAIDs' role in PCa development has been extensively studied; however, there is
      not yet a definitive answer. Moreover, the epidemiological results for NSAIDs'
      effect on PCa-specific mortality have been inconsistent. Therefore, we performed
      a meta-analysis to examine the controversy. METHODS: We performed a literature
      database search and included all published studies conducted in the general
      population exposed to any NSAID, extracting an odds ratio (OR) or a hazard ratio
      (HR) with 95% confidence intervals (95% CIs) that compared the incidence of PCa
      or PCa-specific mortality with non-exposure. We derived a pooled OR or HR using
      random or fixed effects models, as appropriate. Subgroup analyses were also
      performed. RESULTS: Thirty-nine studies (20 case-control and 19 cohort studies)
      were included in this analysis. Thirty-one studies were available concerning
      NSAID use and PCa incidence and eight studies on PCa-specific mortality. Compared
      to non-use, aspirin use was statistically significantly associated with PCa
      incidence risk, and the association was slightly stronger for advanced PCa than
      for total PCa (OR = 0.92, 95% CI = 0.87 to 0.97 for total PCa; OR = 0.81, 95% CI
      = 0.73 to 0.89 for advanced PCa). Aspirin use seems also to be associated with a
      modest reduction in PCa-specific mortality (HR = 0.86, 95% CI = 0.78 to 0.96 for
      total PCa; OR = 0.81, 95% CI = 0.71 to 0.92 for advanced PCa). Generally, the
      pooled effects for any NSAIDs, NA-NSAIDs and cyclooxygenase-2 inhibitors
      demonstrated no adverse or beneficial effects on PCa development or PCa-specific
      mortality, but the results were not consistent. The effect estimates did not vary
      markedly when stratified by study design and study quality but varied by
      geographic region. Furthermore, long-term aspirin use (>= 4 years) was also
      significantly associated with reduced PCa incidence (OR = 0.88, 95% CI 0.79 to
      0.99). CONCLUSIONS: The present meta-analysis provides support for the hypothesis
      that aspirin use is inversely related to PCa incidence and PCa-specific
      mortality. The effect estimates, varying by geographic region, deserve further
      investigation.

PMID- 24678718
TI  - Central extracorporeal life support with left ventricular decompression for the
      treatment of refractory cardiogenic shock and lung failure.
AB  - BACKGROUND: The purpose of this prospective study was to evaluate the effects and
      functional outcome of central extracorporeal life support (ECLS) with left
      ventricular decompression for the treatment of refractory cardiogenic shock and
      lung failure. METHODS: Between August 2010 and August 2013, 12 consecutive
      patients (2 female) with a mean age of 31.6 +/- 15.1 years received central ECLS
      with left ventricular decompression for the treatment of refractory cardiogenic
      shock and lung failure. Underlying disease was acute cardiac decompensation due
      to dilated cardiomyopathy (n = 3, 25%), coronary artery disease with acute
      myocardial infarction (AMI) (n = 3, 25%), and acute myocarditis (n = 6, 50%). We
      routinely implemented ECLS by cannulating the ascending aorta, right atrium and
      inserting a left ventricular decompression cannula vent via the right superior
      pulmonary vein. RESULTS: All patients were successfully bridged to either
      recovery (n = 3, 25%), long-term biventricular support (n = 6, 50%) or cardiac
      transplantation (n = 3, 25%). Seven patients (58.3%) were discharged after a mean
      hospital stay of 42 +/- 11.9 days. The overall survival from ECLS implantation to
      the end of the study was 58.3%. The cumulative ICU stay was 23.1 +/- 9.6 days.
      The length of support was 8.0 +/- 4.3 days (range 3-17 days). CONCLUSIONS: We
      strongly recommend left ventricular decompression in refractory cardiogenic shock
      and lung failure to avoid pulmonary edema, left heart distension and facilitate
      myocardial recovery.

PMID- 24678719
TI  - Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor
      suppressor results in neurologic phenotypes related to schizophrenia.
AB  - BACKGROUND: Loss of adenomatous polyposis coli (APC) gene function results in
      constitutive activation of the canonical Wnt pathway and represents the main
      initiating and rate-limiting event in colorectal tumorigenesis. APC is likely to
      participate in a wide spectrum of biological functions via its different
      functional domains and is abundantly expressed in the brain as well as in
      peripheral tissues. However, the neuronal function of APC is poorly understood.
      To investigate the functional role of Apc in the central nervous system, we
      analyzed the neurological phenotypes of Apc1638T/1638T mice, which carry a
      targeted deletion of the 3' terminal third of Apc that does not affect Wnt
      signaling. RESULTS: A series of behavioral tests revealed a working memory
      deficit, increased locomotor activity, reduced anxiety-related behavior, and
      mildly decreased social interaction in Apc1638T/1638T mice. Apc1638T/1638T mice
      showed abnormal morphology of the dendritic spines and impaired long-term
      potentiation of synaptic transmission in the hippocampal CA1 region. Moreover,
      Apc1638T/1638T mice showed abnormal dopamine and serotonin distribution in the
      brain. Some of these behavioral and neuronal phenotypes are related to symptoms
      and endophenotypes of schizophrenia. CONCLUSIONS: Our results demonstrate that
      the C-terminus of the Apc tumor suppressor plays a critical role in cognitive and
      neuropsychiatric functioning. This finding suggests a potential functional link
      between the C-terminus of APC and pathologies of the central nervous system.

PMID- 24678720
TI  - Hearing, Listening, Action: Enhancing nursing practice through aural awareness
      education.
AB  - Abstract Noise overload within the clinical environment has been found to
      interfere with the healing process for patients, as well as nurses ability to
      effectively assess patients. Awareness and responsibility for noise production
      begins during initial nursing training and consequently a program to enhance
      aural awareness skills was designed for graduate entry nursing students in an
      Australian university. The program utilised an innovative combination of music
      education activities to develop the students' ability to distinguishing
      individual sounds (hearing), appreciate patient's experience of sounds
      (listening) and improve their auscultation skills and reduce the negative effects
      of noise on patients (action). Using a mixed methods approach, students' reported
      heightened auscultation skills and greater recognition of both patients' and
      clinicians' aural overload. Results of this pilot suggest that music education
      activities can assist nursing students to develop their aural awareness and to
      action changes within the clinical environment to improve the patient's
      experience of noise.

PMID- 24678721
TI  - 5-methylcytosine recognition by Arabidopsis thaliana DNA glycosylases DEMETER and
      DML3.
AB  - Methylation of cytosine to 5-methylcytosine (5mC) is important for gene
      expression, gene imprinting, X-chromosome inactivation, and transposon silencing.
      Active demethylation in animals is believed to proceed by DNA glycosylase removal
      of deaminated or oxidized 5mC. In plants, 5mC is removed from the genome directly
      by the DEMETER (DME) family of DNA glycosylases. Arabidopsis thaliana DME excises
      5mC to activate expression of maternally imprinted genes. Although the related
      Repressor of Silencing 1 (ROS1) enzyme has been characterized, the molecular
      basis for 5mC recognition by DME has not been investigated. Here, we present a
      structure-function analysis of DME and the related DME-like 3 (DML3) glycosylases
      for 5mC and its oxidized derivatives. Relative to 5mC, DME and DML3 exhibited
      robust activity toward 5-hydroxymethylcytosine, limited activity for 5
      carboxylcytosine, and no activity for 5-formylcytosine. We used homology modeling
      and mutational analysis of base excision and DNA binding to identify residues
      important for recognition of 5mC within the context of DNA and inside the enzyme
      active site. Our results indicate that the 5mC binding pocket is composed of
      residues from discrete domains and is responsible for discrimination against 5mC
      derivatives, and suggest that DME, ROS1, and DML3 utilize subtly different
      mechanisms to probe the DNA duplex for cytosine modifications. 

PMID- 24678722
TI  - Copper-catalyzed intramolecular cyclization of N-propargyl-adenine: synthesis of
      purine-fused tricyclics.
AB  - A novel protocol to construct fluorescent purine-fused tricyclic products via
      intramolecular cyclization of N-propargyl-adenine has been developed. With CuBr
      as the catalyst, a series of purine-fused tricyclic products were obtained in
      good to excellent yields (19 examples, 75-89% yields). When R2 was a hydrogen
      atom in N-propargyl-adenines, the reactions only afforded the endocyclic double
      bond products. When R2 was an aryl group, the electron-donating groups favored
      the endocyclic double bond products, while the electron-withdrawing groups
      favored the exocyclic double bond products.

PMID- 24678723
TI  - Photoelectrochemical behavior of hierarchically structured Si/WO3 core-shell
      tandem photoanodes.
AB  - WO3 thin films have been deposited in a hierarchically structured core-shell
      morphology, with the cores consisting of an array of Si microwires and the shells
      consisting of a controlled morphology WO3 layer. Porosity was introduced into the
      WO3 outer shell by using a self-assembled microsphere colloidal crystal as a mask
      during the deposition of the WO3 shell. Compared to conformal, unstructured WO3
      shells on Si microwires, the hierarchically structured core-shell photoanodes
      exhibited enhanced near-visible spectral response behavior, due to increased
      light absorption and reduced distances over which photogenerated carriers were
      collected. The use of structured substrates also improved the growth rate of
      microsphere-based colloidal crystals and suggests strategies for the use of
      colloidal materials in large-scale applications. 

PMID- 24678724
TI  - Tamarind kernel powder: a novel agro-residue for the production of cellobiose
      dehydrogenase under submerged fermentation by Termitomyces clypeatus.
AB  - The study investigates the potential of substitution of the conventional
      carbohydrate nutrient (cellulose) in media with cheap agro-residues for
      cellobiose dehydrogenase production by Termitomyces clypeatus (CDHtc) under
      submerged conditions. Different agro-residues tested for enzyme production were
      characterized using FTIR and XRD analysis. As CDHtc production was highest with
      tamarind kernel powder (TKP), it was selected for process optimizations through
      shake-flask fermentations. The optimized parameters were then applied to batch
      cultures in a 5 L bioreactor that gave enzyme yield (57.4 U mL-1) similar to that
      obtained under shake-flask fermentations (57.05 U mL-1). The study also made an
      attempt to predict CDHtc production with respect to time of fermentation and
      mycelial growth. The specific growth rate and carrying capacity of the mycelia
      were also determined, and the values lie in the ranges of 0.024-0.027 h-1 and 7.2
      7.1 mg mL-1, respectively.

PMID- 24678725
TI  - Reproductive health knowledge and services utilization among rural adolescents in
      east Gojjam zone, Ethiopia: a community-based cross-sectional study.
AB  - BACKGROUND: According to World Health Organization, adolescents are people
      between 10 and 19 years of age; one-fifth of Ethiopian population constitutes
      adolescents and four-fifth live in rural areas. Local evidence about adolescents'
      reproductive health knowledge, services utilization and associated factors are
      relevant to design age-appropriate program interventions and strategies. Hence,
      this study assessed the level of reproductive health knowledge and services
      utilization among rural adolescents in Machakel district, Northwest Ethiopia.
      METHODS: A community-based cross-sectional study was conducted to assess the
      level of reproductive health knowledge and services utilization of rural
      adolescents in Machakel district. The study employed both quantitative and
      qualitative methods. A systematic random sampling technique was used to select
      415 adolescents from eligible households. Data were collected using pre-tested
      structured questionnaires and in-depth interview guides. The data were entered
      into Epi Info and analyzed by SPSS software for windows. Univariate, bivariate
      and multivariate analyses were done. RESULT: More than two-third (67%) of the
      adolescents had knowledge about reproductive health. Age (AOR = 3.77, 95% CI: 3.1
      8.98), living arrangement (AOR = 2.21, 95% CI: 1.81-6.04) and economic status
      (AOR = 3.37, 95% CI: 1.65-6.87) were associated with reproductive health
      knowledge. However, only one-fifth (21.5%) of the adolescents had ever used
      reproductive health services including family planning, sexually transmitted
      infections treatment and information, education and communication. Reproductive
      health services utilization was significantly associated with age (AOR = 2.18,
      95% CI: 1.13-8.03) and knowledge for reproductive health (AOR = 1.23, 95% CI:
      1.23-4.21). Parent disapproval, lack of basic information and pressure from
      partners were found to deter adolescents from accessing and using reproductive
      health services. CONCLUSION: Reproductive health knowledge and services
      utilization amongst rural adolescents remained low. Age and economic status were
      significantly associated with reproductive health knowledge; moreover,
      reproductive health services utilization was associated with age and respective
      knowledge for reproductive health. Community-conversation in line with adolescent
      to-adolescent-counseling, peer education and parent-adolescent communication
      should address sensitive topics such as sex education and life skill development.

PMID- 24678726
TI  - Pathophysiology, diagnosis and clinical management of hepatorenal syndrome: from
      classic to new drugs.
AB  - Advanced cirrhosis is frequently associated with renal dysfunction. Hepatorenal
      syndrome (HRS) is characterized by the occurrence of kidney injury in cirrhotic
      patients in the absence of other identifiable causes. HRS is classified in 2
      different types. Type 1 is characterized by acute renal failure and rapid
      functional deterioration of other organs, usually related to a precipitating
      event. Type 2 is characterized by slowly progressive renal failure and refractory
      ascites. Advanced liver disease induces the progression of hemodynamic
      alterations such as arterial vasodilation of splanchnic circulation and
      impairment of cardiac function. The resulting ineffective circulating blood
      volume promotes the activation of both the renin-angiotensin-aldosterone and
      sympathetic nervous system, by an increase of antidiuretic hormone activity, in
      an attempt to restore volemia. Despite fluid retention, ascites and dilutional
      hyponatremia, renal function is often initially preserved by renal production of
      vasodilators. However, further insults can lead to an imbalance between systemic
      vasoconstriction and local renal vasodilation, resulting in progressive renal
      failure. Over the last decade, clinical strategies to prevent HRS have been
      improved by a better understanding of the natural history of renal failure in
      cirrhosis, resulting in a reduction of HRS prevalence in cirrhotic patients.
      Vasoconstrictor drugs may improve renal function, but the effect on mortality has
      not yet been established. Vaptans, nonpeptide vasopressin receptor antagonists,
      may also reduce hyponatraemia and ascites, even if the clinical effects in HRS
      remain unknown. This review updates the pathophysiology, diagnosis and management
      of HRS. 

PMID- 24678727
TI  - Effect of pelletization and addition of steam on the cyclic performance of carbon
      templated, CaO-based CO2 sorbents.
AB  - In this work, we report the development of a synthetic CO2 sorbent that possesses
      a high cyclic CO2 uptake capacity and, in addition, sufficient mechanical
      strength to allow it to be used in fluidized-bed reactors. To overcome the
      problem of elutriation of the original powdered material, the synthetic CO2
      sorbent was pelletized. An important aspect of this work was to assess the effect
      of steam on the cyclic CO2 capture capacity of the original, powdered CO2 sorbent
      and the pelletized material. After 30 cycles of repeated calcination and
      carbonation reactions conducted in a fluidized bed, the CO2 uptake of the pellets
      was 0.29 g of CO2/g of sorbent, a value that is 45% higher than that measured for
      the reference limestone. For the case that carbonation/calcination cycles were
      conducted in a thermogravimetric analyzer under steam-free carbonation
      conditions, the CO2 uptake of the best sorbent was 0.33 g of CO2/g of sorbent
      (after 10 cycles). Importantly, it should be noted that, after 10 cycles using
      wet carbonation conditions, the CO2 uptake of this material increased by 55% when
      compared to dry conditions. This observation was attributed to enhanced solid
      state diffusion in the CaCO3 product layer under wet conditions. However,
      independent of the reaction conditions, the pelletized material showed a lower
      cyclic CO2 uptake when compared to the original powder. A detailed morphological
      characterization of the pellets indicated that the destruction of the primary,
      hollow micrometer-sized spheres during pelletization was responsible for the
      lower cyclic CO2 uptake of the pellets. 

PMID- 24678729
TI  - Parafoveal preview benefit in unspaced and spaced Chinese reading.
AB  - In an eye movement experiment during reading, we compared parafoveal preview
      benefit during the reading of Chinese sentences either in the familiar, unspaced
      format or with spaces inserted between the words. Single-character words or the
      first of a two-character word were either presented normally or were replaced by
      a pseudocharacter in the preview. Results indicate that word spacing increased
      the parafoveal preview benefit but only for the one-character target words. We
      hypothesized that the incorrect preview of the first character of the two
      character word prevented parafoveal processing of the ensuing character(s),
      effectively nullifying any benefits from the spacing. Our results suggest that
      word boundary demarcation allows for more precise focusing of attention. 

PMID- 24678730
TI  - Continuously adjusting CRT therapy: clinical impact of adaptive cardiac
      resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce
      morbidity and mortality in patients with moderate and severe symptomatic
      congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic
      right ventricular (RV) conduction results in similar or even better cardiac
      performance compared to biventricular (Biv) pacing. Optimal programming of the
      atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV
      performance since suboptimal programming of AV and VV delays affect LV filling as
      well as cardiac output. CRT optimization using echocardiogram is resource
      dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic,
      automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing)
      and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for
      CRT-indicated patients without permanent atrial fibrillation. It has been shown
      to improve CRT response and reduce morbidity and mortality for patients with
      normal AV conduction. 

PMID- 24678731
TI  - Coregulation of genetic programs by the transcription factors NFIB and STAT5.
AB  - Mammary-specific genetic programs are activated during pregnancy by the common
      transcription factor signal transducer and activator of transcription (STAT) 5.
      More than one third of these genes carry nuclear factor I/B (NFIB) binding motifs
      that coincide with STAT5 in vivo binding, suggesting functional synergy between
      these two transcription factors. The role of NFIB in this governance was
      investigated in mice from which Nfib had been inactivated in mammary stem cells
      or in differentiating alveolar epithelium. Although NFIB was not required for
      alveolar expansion, the combined absence of NFIB and STAT5 prevented the
      formation of functional alveoli. NFIB controlled the expression of mammary
      specific and STAT5-regulated genes and chromatin immunoprecipitation-sequencing
      established STAT5 and NFIB binding at composite regulatory elements containing
      histone H3 lysine dimethylation enhancer marks and progesterone receptor binding.
      By integrating previously published chromatin immunoprecipitation-sequencing data
      sets, the presence of NFIB-STAT5 modules in other cell types was investigated.
      Notably, genomic sites bound by NFIB in hair follicle stem cells were also
      occupied by STAT5 in mammary epithelium and coincided with enhancer marks. Many
      of these genes were under NFIB control in both hair follicle stem cells and
      mammary alveolar epithelium. We propose that NFIB-STAT5 modules, possibly in
      conjunction with other transcription factors, control cell-specific genetic
      programs.

PMID- 24678732
TI  - Regulation of HER2 oncogene transcription by a multifunctional
      coactivator/corepressor complex.
AB  - Transcription of the HER2 oncogene can be repressed by estrogen (E2). We now show
      that, a splice isoform of the nuclear receptor coactivator AIB1, AIB1-Delta4, is
      able to reverse E2 repression of HER2 gene expression in breast cancer cells. The
      first 224 amino acids of AIB1 that are absent in AIB1-Delta4, bind a co
      repressor, ANCO1. Using chromatin immunoprecipitation assay approaches in MCF7
      and BT474 cell lines, we demonstrate that AIB1 and AIB1-Delta4 can bind to the E2
      regulatory site in the first intron of the HER2 gene, after E2 treatment, but
      only full-length AIB1 recruits ANCO1. Consistent with E2-induced chromatin
      repression, the AIB1-ANCO1 complex recruits HDAC3 and HDAC4 to the intronic
      estrogen response element and the proximal promoter acquires the repressive
      chromatin mark H3K9me3 and loses H3K4me1. In contrast, AIB1-Delta4 does not
      recruit ANCO 1, HDAC3, or HDAC4 and the proximal promoter retains activation
      marks of H3K4me1. In cell lines with low levels of ANCO1 (T47D), E2 does not
      repress HER2 gene transcription but the repressive response can be restored by
      overexpression of ANCO1. ANCO1 can also repress other E2-responsive genes,
      indicating that AIB1, AIB1-Delta4 and ANCO1 are important determinants of
      endocrine and growth factor responsiveness in breast cancer. 

PMID- 24678734
TI  - Research resource: EPSLiM: ensemble predictor for short linear motifs in nuclear
      hormone receptors.
AB  - Nuclear receptors (NRs) are a superfamily of transcription factors central to
      regulating many biological processes, including cell growth, death, metabolism,
      and immune responses. NR-mediated gene expression can be modulated by
      coactivators and corepressors through direct physical interaction or protein
      complexes with functional domains in NRs. One class of these domains includes
      short linear motifs (SLiMs), which facilitate protein-protein interactions,
      phosphorylation, and ligand binding primarily in the intrinsically disordered
      regions (IDRs) of proteins. Across all proteins, the number of known SLiMs is
      limited due to the difficulty in studying IDRs experimentally. Computational
      tools provide a systematic and data-driven approach for predicting functional
      motifs that can be used to prioritize experimental efforts. Accordingly, several
      tools have been developed based on sequence conservation or biophysical features;
      however, discrepancies in predictions make it difficult to determine the true
      candidate SLiMs. In this work, we present the ensemble predictor for short linear
      motifs (EPSLiM), a novel strategy to prioritize the residues that are most likely
      to be SLiMs in IDRs. EPSLiM applies a generalized linear model to integrate
      predictions from individual methodologies. We show that EPSLiM outperforms
      individual predictors, and we apply our method to NRs. The androgen receptor is
      an example with an N-terminal domain of 559 disordered amino acids that contains
      several validated SLiMs important for transcriptional activation. We use the
      androgen receptor to illustrate the predictive performance of EPSLiM and make the
      results of all human and mouse NRs publically available through the web service
      http://epslim.bwh.harvard.edu.

PMID- 24678735
TI  - Role of inflammatory markers in Takayasu arteritis disease monitoring.
AB  - BACKGROUND: Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis that
      can result in significant morbidity and mortality secondary to progressive
      stenosis and occlusion. Monitoring disease progression is crucial to preventing
      relapse, but is often complicated by the lack of clinical symptoms in the setting
      of active disease. Although acute phase reactants such as ESR and CRP are
      generally used as an indicator of inflammation and disease activity, mounting
      evidence suggests that these markers cannot reliably distinguish active from
      inactive TA. CASE PRESENTATION: We report a 24-year-old Hispanic female with a 5
      year history of TA who presented with stroke-like symptoms and evidence of left
      MCA occlusion on imaging, despite a history of decreasing inflammatory markers.
      CTA revealed complete occlusion of the left common carotid artery, left
      subclavian, and left MCA from their origins. It also revealed a striking
      compensatory circulation supplying the left anterior circulation as well as the
      left subclavian as a response to progressive stenosis. CONCLUSION: Monitoring ESR
      and CRP levels alone may not be a reliable method to evaluate disease progression
      in patients with TA, and should be taken in context with both patient's clinical
      picture and the imaging. We recommend that serial imaging be performed regularly
      in the setting of active disease to monitor progression and allow for immediate
      therapy in response to evidence of disease advancement, with a relaxation of the
      imaging interval once the disease is presumed inactive.

PMID- 24678736
TI  - Determining immune components necessary for progression of pigment dispersing
      disease to glaucoma in DBA/2J mice.
AB  - BACKGROUND: The molecular mechanisms causing pigment dispersion syndrome (PDS)
      and the pathway(s) by which it progresses to pigmentary glaucoma are not known.
      Mutations in two melanosomal protein genes (Tyrp1(b) and Gpnmb(R150X)) are
      responsible for pigment dispersing iris disease, which progresses to intraocular
      pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal
      defects along with ocular immune abnormalities play a role in the propagation of
      pigment dispersion and progression to IOP elevation. Here, we tested the role of
      specific immune components in the progression of the iris disease and high IOP.
      RESULTS: We tested the role of NK cells in disease etiology by genetically
      modifying the B6.D2-Gpnmb(R150X) Tyrp1(b) strain, which develops the same iris
      disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK
      mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg
      mutation) has any influence on the severity or timing of Gpnmb(R150X) Tyrp1(b)
      mediated iris disease. Since DBA/2J mice are deficient in CD94, an important
      immune modulator that often acts as an immune suppressor, we generated DBA/2J
      mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris
      disease or the subsequent IOP elevation. Additionally CD94 status had no detected
      effect on glaucomatous optic nerve damage. CONCLUSION: Our previous data
      implicate immune components in the manifestation of pigment dispersion and/or IOP
      elevation in DBA/2J mice. The current study eliminates important immune
      components, specifically NK cells and CD94 deficiency, as critical in the
      progression of iris disease and glaucoma. This narrows the field of possible
      immune components responsible for disease progression.

PMID- 24678733
TI  - Minireview: Metabolism of female reproduction: regulatory mechanisms and clinical
      implications.
AB  - Female fertility is highly dependent on successful regulation of energy
      metabolism. Central processes in the hypothalamus monitor the metabolic state of
      the organism and, together with metabolic hormones, drive the peripheral
      availability of energy for cellular functions. In the ovary, the oocyte and
      neighboring somatic cells of the follicle work in unison to achieve successful
      metabolism of carbohydrates, amino acids, and lipids. Metabolic disturbances such
      as anorexia nervosa, obesity, and diabetes mellitus have clinically important
      consequences on human reproduction. In this article, we review the metabolic
      determinants of female reproduction and their role in infertility.

PMID- 24678737
TI  - Resistant hypertension: is renal denervation the current treatment of choice?
AB  - BACKGROUND: Resistant hypertension is simply defined as failure to control blood
      pressure <140/90 mmHg in an adherent non-diabetic patient with normal kidney
      function despite the use of optimal doses of three antihypertensive agents,
      including a diuretic. Also, control of blood pressure in any adherent patient
      with more than four antihypertensive agents defines resistant hypertension. In a
      patient with diabetes or chronic kidney disease, the goal blood pressure is
      <130/80 mmHg. One of the most important pathophysiological mechanisms of
      resistant hypertension is overactivity of the sympathetic nervous system (SNS).
      In selected patients with resistant hypertension, renal denervation has been
      shown to control blood pressure by suppressing SNS overactivity. SUMMARY: This
      review summarizes the results of the studies of renal denervation for resistant
      hypertension and suggests the use of this procedure in several other conditions
      that are associated with SNS overactivity. KEY MESSAGE: Renal denervation seems
      to control blood pressure in patients with resistant hypertension.

PMID- 24678738
TI  - Antibiotic resistance--consequences for animal health, welfare, and food
      production.
AB  - Most of the literature on the consequences of emergence and spread of bacteria
      resistant to antibiotics among animals relate to the potential impact on public
      health. But antibiotics are used to treat sick animals, and resistance in animal
      pathogens may lead to therapy failure. This has received little scientific
      attention, and therefore, in this article, we discuss examples that illustrate
      the possible impact of resistance on animal health and consequences thereof. For
      all animals, there may be a negative effect on health and welfare when diseases
      cannot be treated. Other consequences will vary depending on why and how
      different animal species are kept. Animals kept as companions or for sports often
      receive advanced care, and antibiotic resistance can lead to negative social and
      economic consequences for the owners. Further, spread of hospital-acquired
      infections can have an economic impact on the affected premises. As to animals
      kept for food production, antibiotics are not needed to promote growth, but, if
      infectious diseases cannot be treated when they occur, this can have a negative
      effect on the productivity and economy of affected businesses. Antibiotic
      resistance in animal bacteria can also have positive consequences by creating
      incentives for adoption of alternative regimes for treatment and prevention. It
      is probable that new antibiotic classes placed on the market in the future will
      not reach veterinary medicine, which further emphasizes the need to preserve the
      efficacy of currently available antibiotics through antibiotic stewardship. A
      cornerstone in this work is prevention, as healthy animals do not need
      antibiotics.

PMID- 24678739
TI  - The interleukin-17/interleukin-22 innate axis in the gut as a new drug target in
      allergic-inflammatory and autoimmune diseases. A working hypothesis.
AB  - The innate lymphoid cells (ILCs) have been grouped into three main categories:
      ILC1s [T helper (h)1-like cells], ILC2s (Th2-like cells) and ILC3s (Th17-like
      cells), respectively. In particular, ILC3s are responsible for the secretion of
      both interleukin (IL)-17 and IL-22, which play either protective (antimicrobial
      and repairing activities) or harmful (inflammation and tumor growth) roles into
      the host. Here, some putative interventional studies will be hypothesized, taking
      into account that activation of innate cell receptors, arylhydrocarbon receptor
      and gut microbiota, respectively, contribute to both differentiation and function
      of ILC3s. A series of biological and natural compounds may represent putative
      regulators of these cells in the gut. In this respect, the modulating effects of
      agonist and antagonists of Toll-like receptors and nucleotide binding
      oligomerization domain-like receptors, polyphenols and probiotics will be
      described in detail. 

PMID- 24678740
TI  - Three alkaloids from Reineckia carnea herba and their antitussive and expectorant
      activities.
AB  - Three alkaloids, (3-chloro-2-hydroxypropyl) trimethylammonium chloride (1), p
      (acetylamino)-phenol (2) and 4,4'-diacetamidodiphenyl ether (3), were isolated
      from Reineckia carnea herba. Their structures were determined by detailed
      analysis of their 1D and 2D NMR spectra and MS. Compounds 1 and 3 were new
      natural products. Compound 2 was isolated for the first time from the Reineckia
      genus. Compound 1 displayed significant in vivo antitussive and expectorant
      activities. 

PMID- 24678741
TI  - The efficacy of tourniquet assisted total knee arthroplasty on patient-reported
      and performance-based physical function: a randomized controlled trial protocol.
AB  - BACKGROUND: Surgical treatment of osteoarthritis with total knee arthroplasty
      (TKA) usually takes place in a complete bloodless field using a tourniquet.
      However, doing the surgery without a tourniquet may reduce muscle damage, post
      surgery pain and led to improved functional rehabilitation and mobilization.
      METHODS/DESIGN: A prospective, blinded, parallel-group, controlled superiority
      trial, with balanced randomization [1:1]. Patients aged 50 or older eligible for
      primary TKA for osteoarthritis will be consecutively recruited from Department of
      Orthopedic Surgery and Traumatology, Odense University Hospital, Denmark. A total
      of 80 patients will be randomly allocated to TKA with or without tourniquet
      application providing 40 patients for each of the two treatment arms. The
      tourniquet assisted TKA group will have an automatic, micro-processor-based
      pneumatic tourniquet inflated around the thigh during surgery. The non-tourniquet
      assisted TKA group will have surgery performed without application of a
      tourniquet. The primary aim is to compare tourniquet assisted to non-tourniquet
      assisted TKA on patient-reported physical function (KOOS-ADL). The secondary aim
      is to compare post-surgery pain, function in sports and recreation, quality of
      life, and performance-based physical function. The explorative outcomes include;
      use of pain medication, single-fiber muscle damage, and changes in mechanical
      muscle function. The primary endpoint will be at 3-months following surgical
      treatment, and the time-point for analysis of the primary outcome. However,
      follow-up will continue up to 1 year, and provide medium-term results. The
      treatment effect (difference in KOOS-ADL) will be analyzed using a random effects
      regression model, crude and adjusted results will be reported, if needed.
      Analyses will be based on the intention-to-treat (ITT). Subsequent per-protocol
      analysis may be necessary in the event of a substantial number of patients (>
      15%) being lost during follow-up. The number needed to treat (NNT) for a positive
      effect of treatment (>10 points on KOOS-ADL) will be reported. DISCUSSION: This
      is the first randomized clinical trial comparing the efficacy of tourniquet
      assisted TKA on patient-reported physical function supported by a range of
      performance-based secondary outcome measures. As such it will provide high
      quality evidence that may help determine whether tourniquet should be used in
      future TKA procedures in patients with osteoarthritis of the knee. TRIAL
      REGISTRATION: ClinicalTrials NCT01891266.

PMID- 24678743
TI  - Evaluation of ovarian reserve and function in female patients treated with oral
      isotretinoin for severe acne: an exploratory study.
AB  - BACKGROUND: Isotretinoin affects the levels of female hormones and ovaries in
      patients with severe acne. OBJECTIVE: This study evaluated the effects of
      isotretinoin on the ovarian reserve and levels of female hormones in patients
      with severe acne. METHODS: Thirty-two female patients with severe acne were
      enrolled. All the patients were treated with oral isotretinoin 0.5-2 mg/kg/d. The
      total cumulative dose for a full course was 120-135 mg/kg. The treatment duration
      ranged from 5 to 8 months. The serum follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), and estradiol (E2) levels and antral follicle count
      (AFC) and ovarian volume (OV) were evaluated before and after treatment. RESULTS:
      After treatment, the mean FSH, LH, and E2 levels were significantly lower than
      before treatment. In addition, the mean AFC and OV decreased after treatment,
      although the difference was not significant. CONCLUSION: The results of this
      exploratory study do not demonstrate that oral isotretinoin has an impact in
      ovarian function. In contrast, isotretinoin affects levels of female hormones in
      patients with severe acne.

PMID- 24678742
TI  - Assessment of a synthetic steroid and flutamide on dopamine, GSH and H2O2 levels
      in rat brain in presence of fructose.
AB  - Flutamide is a drug used in the treatment of androgen-dependent disorders.
      However, this treatment is usually accompanied by some adverse side effects. The
      aim of this work was to analyse the effect of flutamide and to compare this
      effect with that of a synthetic steroid - 3beta-propionyloxy-5-androsten-17-one
      (PPA) - on levels of dopamine and some oxidative stress markers. For this, thirty
      six male young Wistar rats (65g) were recruited and divided into 6 groups. The
      groups were then treated as follows: Group 1 (control), dimethyl sulfoxide
      (DMSO); group 2, flutamide (4 mg/kg); group 3, PPA; group 4, DMSO + fructose;
      group 5, flutamide + fructose; and group 6, PPA + fructose. The treatments were
      administered intraperitoneally at a daily dose of 4 mg/kg for 10 days. In the
      last day of treatment, blood samples were obtained and used to assess the levels
      of glucose and cholesterol. The animals were then sacrificed and their prostate
      gland and brains were obtained for measurement of 5alpha-reductase, glutathione
      (GSH), calcium, H2O2, and dopamine in cortex, hemispheres, and medulla/oblongata,
      using previously validated methods. RESULTS: Dopamine levels decreased while GSH
      increased significantly in cortex and hemispheres of animals that received PPA
      plus fructose. Also in the same group, GSH decreased in cerebellum/medulla
      oblongata when compared with control group. Peroxidation decreased significantly
      in all tissues of the groups, while ATPase activity witnessed a significant
      decrease in cortex and an increase in hemispheres of animal groups treated with
      flutamide and PPA both in combination with fructose. CONCLUSION: The steroid,
      3beta-propionyloxy-5-androsten-17-one, may in part act as a neuroprotector
      mediated by the increase of GSH and decrease of H2O2. Besides, imbalance in
      steroid homeostasis may alter the metabolism of dopamine.

PMID- 24678745
TI  - Efficacy and toxicity of antibacterial agents used in wound dressings.
AB  - Wound dressings have been used to facilitate the process of wound healing.
      Prevention and/or control of infection in the wound and the surrounding areas has
      always been an important expectation for these wound dressings. To provide wound
      dressings that meet such expectations, extensive research efforts have been
      devoted to the development of wound dressings that are incorporated with various
      antibacterial agents via different methods. These antibacterial agents are
      usually expected to work effectively against a broad spectrum of microorganisms,
      while causing little toxicity or allergy to those who use the products. This
      article reviews the antibacterial activity and toxicity of the most frequently
      used antimicrobial agents used in current wound dressings. 

PMID- 24678744
TI  - Ocular findings in breast cancer patients using tamoxifen.
AB  - AIM: To examine ocular findings of breast cancer patients using tamoxifen.
      METHODS: The records of 79 consecutive breast cancer patients were examined,
      retrospectively. Female patients who had previously been diagnosed to have breast
      cancer with either stage I, II, or III disease, and were older than 25 years of
      age were included in the study. Results of the ophthalmic examination, color
      discrimination, and contrast sensitivity tests were recorded. Short wavelength
      automated perimetry (SWAP) sensitivity values were obtained, and average
      sensitivity values of test points at 5 degrees , 9 degrees , 15 degrees , and 21
      degrees  from the fixation were calculated. RESULTS: Forty-nine of the patients
      had received 20 mg daily dose of tamoxifen therapy (tamoxifen group), while
      remaining 30 patients had not used tamoxifen (control group). Anterior and
      posterior segment examination revealed no pathologic findings in both groups. Two
      patients (5%) in the tamoxifen group had diffuse color loss, while none did in
      the control group (p = 0.523). Statistically significant differences were not
      detected between two groups when square roots of total error in color vision, red
      green, and blue-yellow partial error scores were compared. Contrast sensitivity
      values were similar in both groups. Average mean deviation (MD) and average
      sensitivity values of test points at each 4 degrees  were statistically
      significantly lower in the tamoxifen group than the control group (p = 0.002, p =
      0.001, p < 0.001 and p < 0.001 for right eye; p = 0.002, p= 0.001, p < 0.001 and
      p < 0.001 for left eye). Strong correlation was detected between MD, and duration
      (r = -0.832 and r = -0.842 for right and left eyes, respectively) and cumulative
      dose of tamoxifen use (r = -0.864 and r = -0.854 for right and left eyes,
      respectively). CONCLUSION: Clinically significant ocular toxicity is not
      frequently encountered in breast cancer patients, however, SWAP changes may occur
      early after tamoxifen utilization.

PMID- 24678746
TI  - Povidone iodine in the treatment of adenoviral conjunctivitis in infants.
AB  - CONTEXT: Adenoviral conjunctivitis. OBJECTIVE: To examine the effects of
      conjunctival irrigation with povidone iodine in infants with adenoviral
      conjunctivitis. MATERIAL AND METHODS: An outbreak of adenovirus conjunctivitis
      occurred between September and December 2012 at the neonatal intensive care unit
      of our hospital. Forty-three infants with adenoviral conjunctivitis were examined
      in this study. Thirty-five eyes of 35 infants who had detailed ophthalmological
      examination and clinical scoring were included. The conjunctiva of 15 infants
      (Group 1) were irrigated with povidone iodine 2.5% solution and then treated with
      preservative-free artificial tears and preservative-free antibiotic drops. Twenty
      infants (Group 2) were treated only with the same drops with the same posology,
      without conjunctival irrigation with povidone iodine. Patients were examined two
      times a week until the complete recovery. Lid edema, conjunctival chemosis,
      fragility of conjunctival vasculature, pseudomembrane formation, and corneal
      involvement were scored clinically. RESULTS: Twenty patients (57%) were female
      and 15 patients (43%) were male and mean age was 3.1 months (ranged from 1 to 4
      months). No relation was found between gender and clinical scores. Statistically
      significant lower clinical scores were obtained from Group 1. The median recovery
      time was earlier in Group 1 (7 d) than Group 2 (12 d) (p = 0.001). CONCLUSION:
      Conjunctival irrigation with 2.5% povidone iodine is effective in the treatment
      of adenoviral conjunctivitis in infants.

PMID- 24678747
TI  - Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis.
AB  - CONTEXT: Allergy to hydrolyzed wheat protein in facial soap has become a major
      social issue in Japan. It has been reported that the most frequent early symptoms
      of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and
      rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by
      long-term use. OBJECTIVE: We evaluated the relation between tear fluid levels of
      specific IgE for wheat and the features of allergic conjunctivitis. METHODS: A
      prospective, non-randomized, cross-sectional study was conducted in 103 patients
      with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and
      sex-matched healthy control subjects (control group). Specific IgE for wheat was
      measured in tear fluid with an immunochromatography assay, and a skin prick test
      (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction,
      ocular itching, and lacrimation) were assessed in each subject along with the
      activities of daily living (ADL) score and the total ocular symptom score for
      allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for
      various changes of the palpebral and bulbar conjunctiva, as well as for limbal
      and corneal lesions associated with allergic conjunctivitis. RESULTS: The IgE
      positive rate and specific IgE score were both higher in the allergic group than
      in the control group (71.8% versus 40.0% and 1.9 +/- 0.7 versus 1.4 +/- 0.5). A
      positive SPT for wheat was also more frequent in the allergic group than in the
      control group (6.8% versus 0.0%). Within the allergic group, patients with a
      positive SPT had higher specific IgE scores than patients with a negative SPT
      (3.3 +/- 0.5 versus 1.8 +/- 0.6, p < 0.001). In the allergic group, the wheat IgE
      level in tear fluid was correlated with the severity of allergic conjunctivitis
      symptoms, including ocular itching (r = 0.665), tearing (r = 0.672), and the
      total ocular symptom score (r = 0.204). Wheat IgE in tear fluid was also
      correlated with the severity of rhinitis symptoms, including sneezing (r =
      0.610), nose blowing (r = 0.640), and nasal obstruction (r = 0.677). Furthermore,
      the tear fluid wheat IgE score was correlated with five objective features of
      allergic conjunctivitis (p < 0.05). CONCLUSIONS: These results suggest that wheat
      allergy may be involved in the development of allergic conjunctivitis.

PMID- 24678748
TI  - Cutaneous anthrax in Southeast Anatolia of Turkey.
AB  - CONTEXT: Anthrax is a rare disease cause by Bacillus anthracis, a Gram-positive,
      rod-shaped endospore-forming capsuled bacterium. Anthrax is manifest in three
      primary forms: cutaneous, respiratory, and gastrointestinal. Cutaneous anthrax
      accounts for approximately 95% of all cases of anthrax in humans. OBJECTIVE: In
      the present study, we evaluated the clinical diagnosis and treatment of cutaneous
      anthrax, a rare disease that nonetheless remains a serious healthcare problem in
      developing countries. METHODS: The complete medical records of patients diagnosed
      with cutaneous anthrax between January 2001 and December 2012 were examined in a
      retrospective manner. Cutaneous anthrax was diagnosed by the identification of
      typical anthrax lesions and/or the presence of Gram-positive-capsuled bacillus
      after staining with Gram stain and methylen blue in pathology samples obtained
      from these lesions and the presence of characteristic scarring with a history of
      severe swelling, black eschar, and positive response to treatment form the basis
      of diagnosis in cases where cultures were negative for the presence of bacillus.
      RESULTS: A total of 58 patients were admitted to the hospital with cutaneous
      anthrax between January 2001 and December 2012. This included 32 (55.2%) males
      and 26 (44.8%) females, with an age range of 15-82 years and a mean age of 38 +/-
      13.8 years. The incubation period for the infection ranged between 1 and 20 d
      (mean 3.7 +/- 1.4 d). The most common symptoms at the time of hospital referral
      were swelling, redness, and black eschar of the skin. The most common lesion site
      was the hand and fingers (41.3%). Isolated of bacteria was used to diagnose the
      disease in six cases (23.8%), detection of Gram-positive bacillus in samples of
      characteristic lesion material was used in seven (28.5%) cases, and the presence
      of a characteristic lesion was the sole diagnostic criteria in 45 (77.6%) cases.
      Treatment consisted of penicillin G (12 cases), ampicillin-sulbactam (30 cases),
      Cefazolin (12 cases), or ciprofloxacin (4 cases). CONCLUSION: Although the
      prevalence of anthrax is a decreasing worldwide, it remains a significant problem
      in developing countries. Rapid identification of the signs and symptoms of
      cutaneous anthrax is essential for effective treatment. Early supportive
      treatment and appropriate antimicrobial measures are necessary to address this
      potentially life-threatening disease.

PMID- 24678749
TI  - Effect of mydriasis induced by topical 0.5% tropicamide instillation on the
      corneal biomechanical properties in healthy individuals measured by ocular
      response analyzer.
AB  - PURPOSE: This observational study aims to investigate the effects of tropicamide
      (0.5%) on corneal biomechanical properties, with the ocular response analyzer
      (ORA), in healthy individuals. METHODS: Corneal hysteresis (CH), corneal
      resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and
      corneal-compensated intraocular pressure (IOPcc) measurements of 38 (21 female
      and 17 male) healthy individuals, before and after 30 min of 0.5% tropicamide
      instillation, were performed by using the ORA. RESULTS: The mean CH, CRF, IOPg
      and IOPcc measurements of the eyes were 10.2 +/- 1.9 mmHg, 10.3 +/- 2.1 mmHg,
      15.7 +/- 3.4 mmHg, 16.4 +/- 3.3 mmHg pre-tropicamide, and 10.4 +/- 1.7 mmHg, 10.3
      +/- 2.1 mmHg, 15.3 +/- 3.4 mmHg, 15.8 +/- 2.7 mmHg post-tropicamide,
      respectively. The differences between the pre- and post-tropicamide measurements
      of the eyes were insignificant (p = 0.184, p = 0.659, p = 0.294, p = 0.150,
      respectively; paired t-test). CONCLUSIONS: A tropicamide instillation does not
      lead to significant changes in the corneal biomechanical properties. Therefore,
      it can be used safely in disease, i.e. in the diagnosis and follow-up ORA as it
      does not cause any change.

PMID- 24678750
TI  - Dermatotoxicologic clinical solutions: textile dye dermatitis patch testing.
AB  - The authors provide a framework for working up and counseling a patient with
      suspected textile dermatitis, focusing on identifying which textile materials are
      most likely to be the cause of the eczematous lesions, the current clinical
      guidelines, the utility and appropriateness of patch testing, the limitations of
      these guidelines, and our pro tempore recommendations. While there are many
      challenges to correctly identify and counsel patients on how to avoid the
      offending textile products in a patient with suspected textile dye dermatitis,
      there is value in following the guidelines set forth to help identify the
      causative textile(s). Although patch tests can be useful, dermatologists should
      understand the limitations of standardized patch testing for patients with
      suspected textile dye-induced dermatitis. These guidelines are expected to
      increase the likelihood of identifying the causative textile(s), so that patch
      testing can be supplemented with swatch testing and chemical dye extraction to
      help discover the allergenic dye. 

PMID- 24678751
TI  - Bilateral acute iris transillumination following a fumigation therapy: a village
      based traditional method for the treatment of ophthalmomyiasis.
AB  - Bilateral acute iris transillumination (BAIT) is a relatively new clinical entity
      characterized by bilateral acute loss of iris pigment epithelium, iris
      transillumination, pigment dispersion in the anterior chamber and atonic pupilla.
      We report herein a 50-year-old female who presented with bilateral ocular pain,
      severe photophobia and red eyes. One month ago, a fly hit her eye, and she
      instantly complained of a discomfort and sensation of a foreign body in both
      eyes. She used a fumigation therapy, a traditional method for the treatment of
      ophthalmomyiasis. During follow-up examinations, intraocular pressures increased
      over 40 mmHg bilaterally despite maximal medical therapy, which necessitated
      trabeculectomy surgery with mitomycin. This is a typical BAIT case with no
      antecedent fluoroquinolone use or viral disease, but a fumigation therapy. There
      might be a possible relationship between BAIT and traditional fumigation therapy
      or this association might be coincidental, both of which need further evaluation.

PMID- 24678752
TI  - Unusual cause of fatal anthrax meningitis.
AB  - We report the case of fatal anthrax meningoencephalitis in the province of Mus
      located in eastern Anatolia, Turkey. The organism isolated from cerebrospinal
      fluid was identified as Bacillus anthracis. The patient was treated with
      crystallized penicillin G (24 MU/day IV) and ciprofloxacin (2 * 400/day IV), but
      died 5 days after hospitalization. Although it is a rare case, we consider that
      the patients who have skin, respiratory and neurological systems might also have
      hemorrhagic meningitis.

PMID- 24678753
TI  - Oral administration of soy peptides suppresses cognitive decline by induction of
      neurotrophic factors in SAMP8 mice.
AB  - SAMP8 mice have a shorter lifespan and show the dysfunction of the central
      nervous system. We here investigated whether soy peptides (SP) composed mainly of
      di- and tripeptides has the potential to prevent age-dependent cognitive
      impairment. SAMP8 and normal aging mice, SAMR1, were fed a diet supplemented with
      SP or a control diet for 26 weeks to investigate the preventive effects on the
      progression of cognitive decline using the Morris water maze. The SP-fed groups
      in SAMP8 and SAMR1 prevented the decline of cognitive ability compared to their
      controls. Increased expression of neurotrophic factors such as BDNF and NT-3 at
      mRNA and protein levels were observed in the brain of SP-fed mice, especially
      SAMP8. Further, the phosphorylated CREB protein level of SAMP8 was markedly up
      regulated by SP feeding. These suggest that SPs have the potential for prevention
      of cognitive impairment via neurotrophic effects. 

PMID- 24678754
TI  - Influence of posture on the ventilatory pattern and the thoraco-abdominal
      kinematics of patients with chronic obstructive pulmonary disease (COPD).
AB  - OBJECTIVE: Evaluate the influence of posture on ventilatory pattern,
      compartmental distribution of volume of chest wall and thoraco-abdominal
      kinematics of patients with severe chronic obstructive pulmonary disease (COPD).
      DESIGN: Cross-sectional study. METHODS: Twelve, male patients with severe COPD
      (Forced Expiratory Volume in the first second (FEV1) = 24.35 +/- 4.52%, Forced
      Vital Capacity% (FVC%) = 60 +/- 13.39% and relationship FEV1/FVC = 53.42 +/-
      14.47). The distribution of the volume of the ribcage [pulmonary rib cage (Rcp),
      abdominal ribcage (Rca) and abdomen (Ab)] during quiet breathing in a sitting
      position without back support (SWB), sitting with backrest (SB) and supine
      position (SUP) was determined using an opto-electronic plethysmograph. RESULTS:
      The following differences were observed: a greater tidal volume in the SWB
      position when compared to the SB position (p = 0.01); greater expiratory time in
      the SUP position in relation to the SWB (p = 0.03) and SB (p = 0.01); and
      increased abdominal contribution to the tidal volume in the SUP position in
      relation to the SWB (p < 0.01) and SB (p < 0.001). No difference was found in the
      thoraco-abdominal synchrony among the positions. CONCLUSION: Sitting position
      without back support enhances the activation of respiratory muscles by increasing
      the tidal volume and supine position seems to favor lung deflation by increasing
      the expiratory time. It seems appropriate to adopt these positions to optimize
      the ventilation/perfusion relationship and physiotherapeutic intervention in
      different clinical conditions.

PMID- 24678755
TI  - Measurement properties of existing clinical assessment methods evaluating
      scapular positioning and function. A systematic review.
AB  - The aims were to compile a schematic overview of clinical scapular assessment
      methods and critically appraise the methodological quality of the involved
      studies. A systematic, computer-assisted literature search using Medline, CINAHL,
      SportDiscus and EMBASE was performed from inception to October 2013. Reference
      lists in articles were also screened for publications. From 50 articles, 54
      method names were identified and categorized into three groups: (1) Static
      positioning assessment (n = 19); (2) Semi-dynamic (n = 13); and (3) Dynamic
      functional assessment (n = 22). Fifteen studies were excluded for evaluation due
      to no/few clinimetric results, leaving 35 studies for evaluation. Graded
      according to the COnsensus-based Standards for the selection of health
      Measurement INstruments (COSMIN checklist), the methodological quality in the
      reliability and validity domains was "fair" (57%) to "poor" (43%), with only one
      study rated as "good". The reliability domain was most often investigated. Few of
      the assessment methods in the included studies that had "fair" or "good"
      measurement property ratings demonstrated acceptable results for both reliability
      and validity. We found a substantially larger number of clinical scapular
      assessment methods than previously reported. Using the COSMIN checklist the
      methodological quality of the included measurement properties in the reliability
      and validity domains were in general "fair" to "poor". None were examined for all
      three domains: (1) reliability; (2) validity; and (3) responsiveness.
      Observational evaluation systems and assessment of scapular upward rotation seem
      suitably evidence-based for clinical use. Future studies should test and improve
      the clinimetric properties, and especially diagnostic accuracy and
      responsiveness, to increase utility for clinical practice.

PMID- 24678756
TI  - Comparison of changes in supraspinatus muscle thickness in persons with
      subacromial impingement syndrome and asymptomatic adults.
AB  - PURPOSE: To compare changes in supraspinatus muscle thickness in persons with
      subacromial impingement syndrome (SAIS) and asymptomatic adults and to determine
      the reliability of the ultrasound imaging (USI) protocol. SUBJECTS: Twenty-two
      persons with SAIS and 22 age- and gender-matched asymptomatic controls. METHODS:
      Ultrasound images of supraspinatus muscle thickness at rest and at 0 degrees , 30
      degrees , 60 degrees , and 90 degrees  of arm elevation were captured and
      measured. To determine same-day intratester reliability, one examiner imaged the
      same subject twice and two examiners took turns capturing images in order to
      determine same-day intertester reliability. SUBJECTS were asked to return for
      between-day intratester reliability. RESULTS: Statistical analyses revealed a
      larger mean supraspinatus thickness in the SAIS group at the 0 degrees  condition
      than in the asymptomatic group (p < 0.05). Same-day intratester and intertester
      reliability was good with ICC(2,3) = 0.73-0.96 for asymptomatic controls and
      ICC(2,3) = 0.61-0.94 for persons with SAIS. Overall, between-day intratester
      reliability was fair to good for most conditions [ICC(2,3) = 0.31-0.90].
      CONCLUSIONS: The thicker supraspinatus muscles at 0 degrees  in the SAIS group
      may indicate a protective spasm. The USI protocol used in the study demonstrated
      good same-day intratester and intertester reliability for both groups.

PMID- 24678757
TI  - Physical therapy clinic therapeutic ultrasound equipment as a source for
      bacterial contamination.
AB  - A procedure commonly used in physical therapy (PT) clinics is therapeutic
      ultrasound (US). This equipment and associated gel comes in contact with patient
      skin, potentially serving as a reservoir for bacteria. In this study, we sampled
      US heads, gel bottle tips and gel from nine outpatient PT clinics in Southeastern
      Tennessee. Samples were collected using sterile swabs. At the microbiology
      laboratory, these swabs were used to inoculate mannitol salt agar and CHROM-MRSA
      agar (for Staphylococcal species) and tryptic soy broth to determine non-specific
      bacterial contamination. US heads, gel bottle tips and gel had variable levels of
      contamination. Tips of gel bottles had the highest contamination, with 52.7%
      positive for non-specific bacterial contamination and 3.6% positive for
      methicillin-resistant Staphylococcus aureus (MRSA). Contamination of gel by non
      specific bacteria was found in 14.5% of bottles sampled. US heads (35.5% of those
      sampled) had non-specific bacterial contamination, with no MRSA detected.
      Disinfecting US heads after initial swabbing resulted in removal of 90.9% of non
      specific contamination. Gel storage at temperatures below 40  degrees C was found
      to encourage the growth of mesophilic bacteria. This study demonstrates the need
      for better cleaning and storage protocols for US heads and gel bottles in PT
      clinics.

PMID- 24678758
TI  - Manual therapy in the treatment of ankle hemophilic arthropathy. A randomized
      pilot study.
AB  - PURPOSE: Although physiotherapy has demonstrated effectiveness in preventing
      ankle arthropathy compared to prophylaxis treatment from early ages, there have
      been no conclusive studies examining physiotherapy intervention once hemophilic
      arthropathy of the ankle has been established. The aim of this study was to
      evaluate the effectiveness of two physiotherapy interventions, in patients with
      hemophilic arthropathy of the ankle that had not been operated on previously.
      METHOD: Nine patients with hemophilia (mean age of 35.7 SD 11.9 years) were
      randomized to a mobilization group (n = 5) and manual therapy group (n = 4). The
      two physiotherapy interventions were: (1) passive mobilization and stretching;
      and (2) manual orthopaedic therapy, both with proprioception training. The study
      lasted for six weeks, with two sessions a week. Ankle mobility and pain
      perception, lower limb proprioception and quality of life were the outcome
      measures. RESULTS: Both treatments improved all ankle movements (p < 0.05). The
      treatment with passive mobilizations also improved the perception of pain and
      quality of life. Six months later, both groups still had improved articular
      movement with the exception of plantar flexion and continued to perceive less
      pain. CONCLUSIONS: Both physiotherapy interventions improved the range of
      movement and lessened pain in patients with ankle arthropathy. No haemarthrosis
      was recorded during treatment or during the follow-up period.

PMID- 24678759
TI  - Implicit beliefs of ability, approach-avoidance goals and cognitive anxiety among
      team sport athletes.
AB  - People's implicit beliefs of ability have been suggested as an antecedent of
      achievement goal adoption, which has in turn been associated with behavioural,
      cognitive and affective outcomes. This study examined a conditional process model
      with team sport athletes' approach-avoidance achievement goals as mediators
      between their implicit beliefs of sport ability and sport-related cognitive
      anxiety. We expected gender to moderate the paths from implicit beliefs of
      ability to approach-avoidance goals and from approach-avoidance goals to
      cognitive anxiety. Team sport athletes with a mean age of 20 years (163 females
      and 152 males) responded to questionnaires about their implicit beliefs of sport
      ability, approach-avoidance goals and sport-related cognitive anxiety.
      Incremental beliefs, gender and the interaction between them predicted mastery
      approach goals. Gender also predicted mastery-avoidance goals, with females
      reporting higher levels than males. Mastery-avoidance goals, gender and the
      interaction between them predicted cognitive anxiety, with females reporting
      higher levels of anxiety than males. Entity beliefs positively predicted
      performance-avoidance goals and the interaction between performance-approach and
      gender predicted anxiety. The indirect effects also showed gender differences in
      relation to performance-approach goals. Taken together, our results suggest that
      coaches trying to create a facilitating climate for their male and female
      athletes may be wise to consider their athletes' anxiety and achievement goal
      patterns as these may affect both the athletes' well-being and performance.

PMID- 24678760
TI  - Reciprocity in microbiome and immune system interactions and its implications in
      disease and health.
AB  - Adaptation of the whole microbial normal flora residing in a host to its natural
      habitat over an evolutionary peroid has resulted in peaceful coexistence with
      mutual benefits for both microbiota and host in steady state. This symbiotic
      relationship between host and microbiota has a significant impact on shaping the
      immune response in the host to achieve an immune tolerance to microbiota but
      retaining the ability to respond to invading pathogens. Perturbation of this
      balance by manipulation of microbial communities in the host can lead to immune
      dysregulation and susceptibility to diseases. By studying the host in the absence
      of microbiota or with alteration of microbiota the complexity of microbial impact
      on the immune system can be resolved. Conversely, the study of microbiota in the
      absence of immune system factors can show how the immune system contributes to
      preservation of the host-microbiota balance. The absence of molecules involved in
      innate or adaptive immunity in knockout models can perturb the balance between
      host and microbiota further adding to more immune dysregulation. A better
      understanding of Microbiome-immune system interaction provides a new opportunity
      to identify biomarkers and drug targets. This will allow the development of new
      therapeutic agents for modulating the immune system to improve health with little
      or no toxicity. The study of interplay between host and microbiota has a
      promising role in the design of therapeutic interventions for immunopathological
      diseases arising from imbalanced host and microbiota interactions. 

PMID- 24678761
TI  - Healthy living in pregnancy: a cluster-randomized controlled trial to prevent
      excessive gestational weight gain - rationale and design of the GeliS study.
AB  - BACKGROUND: Recent studies suggest that excessive gestational weight gain (GWG)
      leads to adverse maternal and fetal outcomes including weight retention in the
      mother and an increased risk of childhood obesity in the offspring.The aim of the
      GeliS study is to examine the effect of a lifestyle intervention programme during
      pregnancy to avoid excessive GWG and, hence, to reduce pregnancy and obstetric
      complications as well as the risk of maternal and offspring obesity. METHODS AND
      DESIGN: The GeliS study is a multicentre cluster-randomized controlled trial. A
      total number of 2500 pregnant women (singleton pregnancy) with a pre-pregnancy
      BMI >= 18.5 kg/m2 and <= 40 kg/m2 will be recruited in practices of
      gynaecologists and midwives in ten Bavarian regions. The intervention comprises
      three structured and individualised counselling sessions on a healthy diet,
      regular physical activity as well as weight monitoring during pregnancy and one
      session after delivery, respectively. The counselling sessions are attached to
      routine pre- and postnatal visits using standardised materials and procedures. In
      the control regions, general recommendations for a healthy lifestyle are given.
      An oral glucose tolerance test is offered to all participants.The primary outcome
      is the proportion of participants with excessive GWG. Secondary outcomes include
      pregnancy and obstetric complications such as frequency of gestational diabetes,
      preeclampsia and caesarean sections as well as weight retention in the mothers
      and BMI and other health variables in the offspring. A 5-year follow-up of both
      mothers and their infants is planned. DISCUSSION: The GeliS lifestyle
      intervention programme has been adapted to the existing routine health care
      system for pregnant women. If shown to be effective, it could be immediately
      implemented in routine care. TRIAL REGISTRATION: The study protocol is registered
      at the ClinicalTrials.gov Protocol Registration System (NCT01958307).

PMID- 24678762
TI  - A combined index to classify prognostic comorbidity in candidates for radical
      prostatectomy.
AB  - BACKGROUND: In patients with early prostate cancer, stratification by comorbidity
      could be of importance in clinical decision making as well as in characterizing
      patients enrolled into clinical trials. In this study, we investigated several
      comorbidity classifications as predictors of overall mortality after radical
      prostatectomy, searching for measures providing complementary prognostic
      information which could be combined into a single score. METHODS: The study
      sample consisted of 2205 consecutive patients selected for radical prostatectomy
      with a mean age of 64 years and a mean follow-up of 9.2 years (median: 8.6).
      Seventy-four patients with incomplete tumor-related data were excluded. In
      addition to age and tumor-related parameters, six comorbidity classifications and
      the body mass index were assessed as possible predictors of overall mortality.
      Kaplan-Meier curves and Mantel-Haenszel hazard ratios were used for univariate
      analysis. The impact of different causes of death was analyzed by competing risk
      analysis. Cox proportional hazard models were calculated to analyze combined
      effects of variables. RESULTS: Age, Gleason score, tumor stage, Charlson score,
      American Society of Anesthesiologists (ASA) physical status class and body mass
      index were identified a significant predictors of overall mortality in the
      multivariate analysis regardless whether two-sided and three-sided
      stratifications were used. Competing risk analysis revealed that the excess
      mortality in patients with a body mass index of 30 kg/m2 or higher was
      attributable to competing mortality including second cancers, but not to prostate
      cancer mortality. CONCLUSION: Stratifying patients by a combined consideration of
      the comorbidity measures Charlson score, ASA classification and body mass index
      may assist clinical decision making in elderly candidates for radical
      prostatectomy.

PMID- 24678763
TI  - Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells
      and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse
      model.
AB  - BACKGROUND: Cancer stem cells (CSCs) play a key role in the posthepatectomy
      recurrence of hepatocellular carcinoma (HCC). CD133+ HCC cells exhibit liver CSC
      like properties, and CSC differentiation-inducing therapy may lead these cells to
      lose their self-renewal ability and may induce terminal differentiation, which
      may in turn allow their malignant potential to be controlled. Because arsenic
      trioxide (As2O3) increases remission rates and prolongs survival among patients
      with acute promyelocytic leukemia by inducing differentiation and apoptosis of
      leukemic cells, we hypothesized that As2O3 might also inhibit HCC recurrence and
      prolong survival time after hepatectomy by inducing differentiation of HCC CSCs.
      METHODS: We evaluated the As2O3 induced differentiation of human HCC CSCs and its
      mechanism in vitro, and we investigated the effects of treatment with As2O3 on
      recurrence rates and median survival in a mouse xenograft model. RESULTS: We
      found that As2O3 induced HCC CSC differentiation by down-regulating the
      expression of CD133 and some stemness genes, thus inhibiting the cells' self
      renewal ability and tumorigenic capacity without inhibiting their proliferation
      in vitro. In vivo experiments indicated that As2O3 decreased recurrence rates
      after radical resection and prolonged survival in a mouse model. As2O3, which
      shows no apparent toxicity, may induce HCC CSC differentiation by down-regulating
      the expression of GLI1. CONCLUSIONS: We found that As2O3 induced HCC CSC
      differentiation, inhibited recurrence, and prolonged survival after hepatectomy
      by targeting GLI1expression. Our results suggest that the clinical safety and
      utility of As2O3 should be further evaluated.

PMID- 24678764
TI  - The safety attitudes questionnaire - ambulatory version: psychometric properties
      of the Norwegian translated version for the primary care setting.
AB  - BACKGROUND: Patient safety culture is how leader and staff interaction,
      attitudes, routines and practices protect patients from adverse events in
      healthcare. The Safety Attitudes Questionnaire is the most widely used instrument
      to measure safety attitudes among health care providers. The instrument may
      identify possible weaknesses in clinical settings, and motivate and guide quality
      improvement interventions and reductions in medical errors. The Safety Attitudes
      Questionnaire - Ambulatory Version was developed for measuring safety culture in
      the primary care setting. The original version includes six major patient safety
      factors: Teamwork climate, Safety climate, Job satisfaction, Perceptions of
      management, Working conditions and Stress recognition. We describe the results of
      a validation study using the Norwegian translation of the questionnaire in the
      primary care setting, and present the psychometric properties of this version.
      METHODS: The study was done in seven Out-of-hours casualty clinics and 17 regular
      GP practices employing a total of 510 primary health care providers (194 nurses
      and 316 medical doctors). In October and November 2012, the translated Safety
      Attitudes Questionnaire - Ambulatory Version was distributed by e-mail. Data were
      collected electronically using the program QuestBack, whereby the participants
      responded anonymously. SPSS was used to estimate the Cronbach's alphas, item-to
      own-factor correlations, intercorrelations of factors and item-descriptive
      statistics. The confirmatory factor analysis was done by AMOS. RESULTS: Of the
      510 invited health care providers, 266 (52%) answered the questionnaire - 72% of
      the registered nurses (n = 139) and 39% of the medical doctors (n = 124). In the
      confirmatory factor analysis, the following five factor model was shown to have
      acceptable goodness-of-fit values in the Norwegian primary care setting: Teamwork
      climate, Safety climate, Job satisfaction, Working conditions and Perceptions of
      management. CONCLUSIONS: The results of our study indicate that the Norwegian
      translated version of the Safety Attitudes Questionnaire - Ambulatory Version,
      with the five confirmed factors, might be a useful tool for measuring several
      aspects of patient safety culture in the primary care setting. Further research
      should investigate whether there is an association between patient safety culture
      in primary care, as measured by the Safety Attitudes Questionnaire - Ambulatory
      Version, and occurrence of medical errors and negative patient outcome.

PMID- 24678765
TI  - Facilitators and barriers to adherence to urate-lowering therapy in African
      Americans with gout: a qualitative study.
AB  - INTRODUCTION: Limited literature exists for qualitative studies of medication
      adherence in gout, especially in African-Americans. The aim of this study was to
      examine the facilitators and barriers to adherence to urate-lowering therapy
      (ULT) in African-Americans with gout. METHODS: In this study, nine nominal groups
      lasting 1 to 1.5 hours each were conducted in African-Americans with gout, six
      with low ULT and three with high ULT adherence (medication possession ratios of
      <0.80 or >=0.80, respectively). Patients presented, discussed, combined and rank
      ordered their concerns. A qualitative analysis was performed. RESULTS: This study
      included 43 patients with mean age 63.9 years (standard deviation, 9.9), 67% men,
      who participated in nine nominal groups (seven in men, two in women): African
      American men (n = 30); African-American women (n = 13). The main facilitators to
      ULT adherence (three groups) were the recognition of the need to take ULT
      regularly to prevent gout flares, prevent pain from becoming chronic/severe and
      to have less dietary restriction; the lack of side effects from ULT; trust in
      physicians; and avoiding the need to seek emergent/urgent care for flares.
      Patients achieved high ULT adherence by organizing their pills using the pillbox
      and the incorporation of ULT intake into their routine to prevent forgetting. The
      main barriers to optimal ULT adherence were (six groups): doubts about
      effectiveness of ULT, concerns about cost and side effects, concomitant
      medications, forgetfulness, refilling the prescriptions on time, pill size and
      difficulty in swallowing, competing priorities, patient preference for
      alternative medicines (that is, cherry juice) and frequent travel. CONCLUSIONS:
      Identification of facilitators and barriers to high ULT adherence in African
      Americans with gout in this study lays the foundation for designing interventions
      to improve ULT adherence in racial minorities.

PMID- 24678766
TI  - Sensitive and comprehensive detection of chemical warfare agents in air by
      atmospheric pressure chemical ionization ion trap tandem mass spectrometry with
      counterflow introduction.
AB  - A highly sensitive and specific real-time field-deployable detection technology,
      based on counterflow air introduction atmospheric pressure chemical ionization,
      has been developed for a wide range of chemical warfare agents (CWAs) comprising
      gaseous (two blood agents, three choking agents), volatile (six nerve gases and
      one precursor agent, five blister agents), and nonvolatile (three lachrymators,
      three vomiting agents) agents in air. The approach can afford effective chemical
      ionization, in both positive and negative ion modes, for ion trap multiple-stage
      mass spectrometry (MS(n)). The volatile and nonvolatile CWAs tested provided
      characteristic ions, which were fragmented into MS(3) product ions in positive
      and negative ion modes. Portions of the fragment ions were assigned by laboratory
      hybrid mass spectrometry (MS) composed of linear ion trap and high-resolution
      mass spectrometers. Gaseous agents were detected by MS or MS(2) in negative ion
      mode. The limits of detection for a 1 s measurement were typically at or below
      the microgram per cubic meter level except for chloropicrin (submilligram per
      cubic meter). Matrix effects by gasoline vapor resulted in minimal false-positive
      signals for all the CWAs and some signal suppression in the case of mustard gas.
      The moisture level did influence the measurement of the CWAs. 

PMID- 24678767
TI  - Terminalia paniculata bark extract attenuates non-alcoholic fatty liver via down
      regulation of fatty acid synthase in high fat diet-fed obese rats.
AB  - BACKGROUND: This study was performed to understand the possible therapeutic
      activity of Terminalia paniculata ethanolic extract (TPEE) on non alcoholic fatty
      liver in rats fed with high fat diet. METHODS: Thirty six SD rats were divided
      into 6 groups (n = 6): Normal control (NC), high fat diet (HFD), remaining four
      groups were fed on HFD along with different doses of TPEE (100,150 and 200 mg/kg
      b.wt) or orlistat, for ten weeks. Liver tissue was homogenized and analyzed for
      lipid profiles, activities of superoxide dismutase (SOD), catalase (CAT) and
      malondialdehyde (MDA) content. Further, the expression levels of FAS and AMPK
      1alpha were also studied in addition to histopathology examination of liver
      tissue in all the groups. RESULTS: HFD significantly increased hepatic liver
      total cholesterol (TC), triglycerides (TG), free fatty acids (FFA) and MDA but
      decreased the activities of SOD and CAT which were subsequently reversed by
      supplementation with TPEE in a dose-dependent manner. In addition, TPEE
      administration significantly down regulated hepatic mRNA expression of FAS but up
      regulated AMPK-1alpha compared to HFD alone fed group. Furthermore, western blot
      analysis of FAS has clearly demonstrated decreased expression of FAS in HFD +
      TPEE (200 mg/kg b.wt) treated group when compared to HFD group at protein level.
      CONCLUSIONS: Our biochemical studies on hepatic lipid profiles and antioxidant
      enzyme activities supported by histological and expression studies suggest a
      potential therapeutic role for TPEE in regulating obesity through FAS.

PMID- 24678768
TI  - Emergence and spread of antibiotic resistance: setting a parameter space.
AB  - The emergence and spread of antibiotic resistance among human pathogens is a
      relevant problem for human health and one of the few evolution processes amenable
      to experimental studies. In the present review, we discuss some basic aspects of
      antibiotic resistance, including mechanisms of resistance, origin of resistance
      genes, and bottlenecks that modulate the acquisition and spread of antibiotic
      resistance among human pathogens. In addition, we analyse several parameters that
      modulate the evolution landscape of antibiotic resistance. Learning why some
      resistance mechanisms emerge but do not evolve after a first burst, whereas
      others can spread over the entire world very rapidly, mimicking a chain reaction,
      is important for predicting the evolution, and relevance for human health, of a
      given mechanism of resistance. Because of this, we propose that the emergence and
      spread of antibiotic resistance can only be understood in a multi-parameter
      space. Measuring the effect on antibiotic resistance of parameters such as
      contact rates, transfer rates, integration rates, replication rates,
      diversification rates, and selection rates, for different genes and organisms,
      growing under different conditions in distinct ecosystems, will allow for a
      better prediction of antibiotic resistance and possibilities of focused
      interventions.

PMID- 24678769
TI  - Phage therapy--constraints and possibilities.
AB  - The rise of antibiotic-resistant bacterial strains, causing intractable
      infections, has resulted in an increased interest in phage therapy. Phage therapy
      preceded antibiotic treatment against bacterial infections and involves the use
      of bacteriophages, bacterial viruses, to fight bacteria. Virulent phages are
      abundant and have proven to be very effective in vitro, where they in most cases
      lyse any bacteria within the hour. Clinical trials on animals and humans show
      promising results but also that the treatments are not completely effective. This
      is partly due to the studies being carried out with few phages, and with limited
      experimental groups, but also the fact that phage therapy has limitations in
      vivo. Phages are large compared with small antibiotic molecules, and each phage
      can only infect one or a few bacterial strains. A very large number of different
      phages are needed to treat infections as these are caused by genetically
      different strains of bacteria. Phages are effective only if enough of them can
      reach the bacteria and increase in number in situ. Taken together, this entails
      high demands on resources for the construction of phage libraries and the testing
      of individual phages. The effectiveness and host range must be characterized, and
      immunological risks must be assessed for every single phage.

PMID- 24678770
TI  - Role of the TLR4 pathway in blood-spinal cord barrier dysfunction during the
      bimodal stage after ischemia/reperfusion injury in rats.
AB  - BACKGROUND: Spinal cord ischemia-reperfusion (I/R) involves two-phase injury,
      including an initial acute ischemic insult and subsequent inflammatory
      reperfusion injury, resulting in blood-spinal cord barrier (BSCB) dysfunction
      involving the TLR4 pathway. However, the correlation between TLR4/MyD88-dependent
      and TLR4/TRIF-dependent pathways in BSCB dysfunction is not fully understood. The
      aim of this study is to characterize inflammatory responses in spinal cord I/R
      and the events that define its clinical progression with delayed neurological
      deficits, supporting a bimodal mechanism of injury. METHODS: Rats were
      intrathecally pretreated with TAK-242, MyD88 inhibitory peptide, or Resveratrol
      at a 12 h interval for 3 days before undergoing 14-minute occlusion of aortic
      arch. Evan's Blue (EB) extravasation and water content were detected at 6, 12,
      18, 24, 36, 48, and 72 h after reperfusion. EB extravasation, water content, and
      NF-kappaB activation were increased with time after reperfusion, suggesting a
      bimodal distribution, as maximal increasing were detected at both 12 and 48 h
      after reperfusion. The changes were directly proportional to TLR4 levels
      determined by Western blot. Double-labeled immunohistochemical analysis was also
      used to detect the relationship between different cell types of BSCB with TLR4.
      Furthermore, NF-kappaB and IL-1beta were analyzed at 12 and 48 h to identify the
      correlation between MyD88-dependent and TRIF-dependent pathways. RESULTS: Rats
      without functional TLR4 and MyD88 attenuated BSCB leakage and inflammatory
      responses at 12 h, suggesting the ischemic event was largely mediated by MyD88
      dependent pathway. Similar protective effects observed in rats with depleted
      TLR4, MyD88, and TRIF receptor at 48 h infer that the ongoing inflammation which
      occurred in late phase was mainly initiated by TRIF-dependent pathway and such
      inflammatory response could be further amplified by MyD88-dependent pathway.
      Additionally, microglia appeared to play a major role in early phase of
      inflammation after I/R injury, while in late responding phase both microglia and
      astrocytes were necessary. CONCLUSIONS: These findings indicate the relevance of
      TLR4/MyD88-dependent and TLR4/TRIF-dependent pathways in bimodal phases of
      inflammatory responses after I/R injury, corresponding with the clinical
      progression of injury and delayed onset of symptoms. The clinical usage of TLR4
      signaling inhibitors at different phases may be a therapeutic option for the
      prevention of delayed injury.

PMID- 24678771
TI  - The influence of trigger factors on hereditary angioedema due to C1-inhibitor
      deficiency.
AB  - BACKGROUND: Hereditary angioedema (HAE) resulting from C1-inhibitor deficiency is
      characterized by attacks of subcutaneous and submucosal edema. Many factors have
      been presumed to induce edema. Our study analyzed these factors in a fairly large
      patient population. METHODS: In the first stage of our study, we analyzed the
      data recorded by 92 subjects in their patient diaries over seven years. The
      second phase included 27 HAE patients, who had been completing the diary entry
      'Trigger factors' every day for seven months whether or not they had experienced
      an attack. RESULTS: During the initial stage, 91% of the subjects described some
      factor possibly related to the onset of an attack. They could identify a trigger
      factor - most commonly (21%) mental stress - in 30% of the 3176 attacks. We found
      a significant (p < 0.001) difference in the distribution of the trigger factors
      of the edematous attacks of different locations. The 27 participants of the
      second phase identified 882 potential trigger factors and recorded 365 attacks.
      Of these, 246 (67%) occurred on days when the patients identified a potential
      trigger factor. The likelihood of edema-formation associated with the latter was
      as follows: menstruation - 63%, infection - 38%, mental stress - 26%, physical
      exertion - 25%, meteorological changes - 21%, fatigue - 17%. CONCLUSION: This
      analysis of the trigger factors explored, for the first time, their potential
      role in inducing HAE attacks. Our findings might open new perspectives in
      extending the indications for edema-prophylaxis, and could contribute to a better
      understanding of the pathomechanism of HAE attacks.

PMID- 24678772
TI  - Association of meteorological factors and seasonality with preeclampsia: a 5-year
      study in northeast of Iran.
AB  - BACKGROUND: Preeclampsia is one of the common causes of maternal and fetal
      mortality, and an important problem of pregnancy. This disorder can cause
      intracranial hemorrhage, intravascular coagulation, pulmonary edema, liver and
      renal failures and placental abruption. OBJECTIVE: To evaluate the effects of
      seasonal and monthly changes of weather, humidity and temperature on the
      incidence rate of preeclampsia according to the conception and delivery times.
      MATERIALS AND METHODS: Retrospective analysis of hospital records of 20,520
      consecutive singleton live birth pregnancies of 20-42 weeks of gestation during
      2002-2008 was performed. After including preeclamptic cases, on the basis of
      American College of obstetricians and gynecologists (ACOG) criteria, gestational
      age and time of conception was estimated and the mean relative temperature and
      humidity of each month was derived from monthly climatological data collection of
      IRAN METEOROLOGICAL ORGANIZATION (IRIMO) between 22 June 2002 and 19 March 2008
      (68 months). Statistics of each month's births were registered separately.
      RESULTS: Mean maternal age of 262 qualified singleton pregnant women with
      preeclampsia out of 20,520 deliveries were 26.48 years old and 85.9% of
      deliveries were done by cesarean section method. Based on time of conception, the
      highest prevalence was detected in summer, especially in September (11.06875%)
      and August (10.3053%) and the lowest prevalence was found in winter and early
      spring, especially in January (5.7552%) and April (5.7252%). CONCLUSION: Seasonal
      (monthly) variations of the weather (humidity and temperature) have a significant
      impression on preeclampsia prevalence.

PMID- 24678773
TI  - Comparison of somatic mutation calling methods in amplicon and whole exome
      sequence data.
AB  - BACKGROUND: High-throughput sequencing is rapidly becoming common practice in
      clinical diagnosis and cancer research. Many algorithms have been developed for
      somatic single nucleotide variant (SNV) detection in matched tumor-normal DNA
      sequencing. Although numerous studies have compared the performance of various
      algorithms on exome data, there has not yet been a systematic evaluation using
      PCR-enriched amplicon data with a range of variant allele fractions. The recently
      developed gold standard variant set for the reference individual NA12878 by the
      NIST-led "Genome in a Bottle" Consortium (NIST-GIAB) provides a good resource to
      evaluate admixtures with various SNV fractions. RESULTS: Using the NIST-GIAB gold
      standard, we compared the performance of five popular somatic SNV calling
      algorithms (GATK UnifiedGenotyper followed by simple subtraction, MuTect,
      Strelka, SomaticSniper and VarScan2) for matched tumor-normal amplicon and exome
      sequencing data. CONCLUSIONS: We demonstrated that the five commonly used somatic
      SNV calling methods are applicable to both targeted amplicon and exome sequencing
      data. However, the sensitivities of these methods vary based on the allelic
      fraction of the mutation in the tumor sample. Our analysis can assist researchers
      in choosing a somatic SNV calling method suitable for their specific needs.

PMID- 24678774
TI  - 4'-C-[(4-trifluoromethyl-1H-1,2,3-triazol-1-yl)methyl]thymidine as a sensitive
      (19)F NMR sensor for the detection of oligonucleotide secondary structures.
AB  - 4'-C-[(4-Trifluoromethyl-1H-1,2,3-triazol-1-yl)methyl]thymidine was synthesized
      and incorporated as a phosphoramidite into oligonucleotide sequences. Its
      applicability as a sensor for the (19)F NMR spectroscopic detection of DNA and
      RNA secondary structures was demonstrated. On DNA, the (19)F NMR measurements
      were focused on monitoring of duplex-triplex conversion, for which this fluorine
      labeled 2'-deoxynucleoside proved to be a powerful sensor. This sensor seemingly
      favors DNA, but its behavior in the RNA environment also turned out to be
      informative. As a demonstration, invasion of a 2'-O-methyl oligoribonucleotide
      into an RNA hairpin model (HIV-1 TAR) was monitored by (19)F NMR spectroscopy.
      According to the thermal denaturation studies by UV spectroscopy, the effect of
      the 4'-C-(4-trifluoromethyl-1H-1,2,3-triazol-1-yl)methyl moiety on the stability
      of these DNA and RNA models was marginal.

PMID- 24678775
TI  - The role of tyrosine kinases in systemic lupus erythematosus and their potential
      as therapeutic targets.
AB  - The autoimmune disease systemic lupus erythematosus is characterized by loss of
      tolerance to nuclear antigens. Breakdown of tolerance is associated with
      alterations in T-cell and B-cell receptor signal transduction, including
      increased protein phosphorylation that may underlie pathogenesis and explain the
      characteristic hyperactivity of T and B cells and other immune cells in active
      disease. Tyrosine kinases play a central role in signaling processes in cells
      known to be important in the pathogenesis of autoimmune diseases. Considerable
      progress has been made in understanding the function of tyrosine kinases in
      immune cell signaling pathways. In this review, we will summarize the function of
      tyrosine kinases and their novel inhibitors from studies made in animal lupus
      models and systemic lupus erythematosus patients.

PMID- 24678776
TI  - De novo VHL germline mutation detected in a patient with mild clinical phenotype
      of von Hippel-Lindau disease.
AB  - Von Hippel-Lindau (VHL) disease is an autosomal dominant multiorgan tumor
      syndrome caused by a germline mutation in the VHL gene. Characteristic tumors
      include CNS hemangioblastomas (HBs), endolymphatic sac tumors, renal cell
      carcinomas, pheochromocytomas, and pancreatic neuroendocrine tumors. Sporadic VHL
      disease with a de novo germline mutation is rare. The authors describe a case of
      multiple CNS HBs in a patient with a heterozygous de novo germline mutation at
      c.239G>T [p.S80I] of VHL. This is the first known case of a sporadic de novo
      germline mutation of VHL at c.239G>T. Clinicians should continue to consider VHL
      disease in patients presenting with sporadic CNS HBs, including those without a
      family history, to confirm or exclude additional VHL-associated visceral lesions.

PMID- 24678777
TI  - Gamma Knife radiosurgery for sellar and parasellar meningiomas: a multicenter
      study.
AB  - OBJECT: Parasellar and sellar meningiomas are challenging tumors owing in part to
      their proximity to important neurovascular and endocrine structures. Complete
      resection can be associated with significant morbidity, and incomplete resections
      are common. In this study, the authors evaluated the outcomes of parasellar and
      sellar meningiomas managed with Gamma Knife radiosurgery (GKRS) both as an
      adjunct to microsurgical removal or conventional radiation therapy and as a
      primary treatment modality. METHODS: A multicenter study of patients with benign
      sellar and parasellar meningiomas was conducted through the North American Gamma
      Knife Consortium. For the period spanning 1988 to 2011 at 10 centers, the authors
      identified all patients with sellar and/or parasellar meningiomas treated with
      GKRS. Patients were also required to have a minimum of 6 months of imaging and
      clinical follow-up after GKRS. Factors predictive of new neurological deficits
      following GKRS were assessed via univariate and multivariate analyses. Kaplan
      Meier analysis and Cox multivariate regression analysis were used to assess
      factors predictive of tumor progression. RESULTS: The authors identified 763
      patients with sellar and/or parasellar meningiomas treated with GKRS. Patients
      were assessed clinically and with neuroimaging at routine intervals following
      GKRS. There were 567 females (74.3%) and 196 males (25.7%) with a median age of
      56 years (range 8-90 years). Three hundred fifty-five patients (50.7%) had
      undergone at least one resection before GKRS, and 3.8% had undergone prior
      radiation therapy. The median follow-up after GKRS was 66.7 months (range 6-216
      months). At the last follow-up, tumor volumes remained stable or decreased in
      90.2% of patients. Actuarial progression-free survival rates at 3, 5, 8, and 10
      years were 98%, 95%, 88%, and 82%, respectively. More than one prior surgery,
      prior radiation therapy, or a tumor margin dose < 13 Gy significantly increased
      the likelihood of tumor progression after GKRS. At the last clinical follow-up,
      86.2% of patients demonstrated no change or improvement in their neurological
      condition, whereas 13.8% of patients experienced symptom progression. New or
      worsening cranial nerve deficits were seen in 9.6% of patients, with cranial
      nerve (CN) V being the most adversely affected nerve. Functional improvements in
      CNs, especially in CNs V and VI, were observed in 34% of patients with
      preexisting deficits. New or worsened endocrinopathies were demonstrated in 1.6%
      of patients; hypothyroidism was the most frequent deficiency. Unfavorable outcome
      with tumor growth and accompanying neurological decline was statistically more
      likely in patients with larger tumor volumes (p = 0.022) and more than 1 prior
      surgery (p = 0.021). CONCLUSIONS: Gamma Knife radiosurgery provides a high rate
      of tumor control for patients with parasellar or sellar meningiomas, and tumor
      control is accompanied by neurological preservation or improvement in most
      patients.

PMID- 24678778
TI  - Resolution of papilledema after endoscopic third ventriculostomy versus
      cerebrospinal fluid shunting in hydrocephalus: a comparative study.
AB  - OBJECT: In this study the authors compare the efficacy of endoscopic third
      ventriculostomy (ETV) versus CSF shunting for resolution of papilledema in
      hydrocephalus. METHODS: This comparative case series study recruited 12 patients
      (24 eyes) with hydrocephalus who underwent either an ETV (Group 1, 6 patients [12
      eyes]) or CSF shunt treatment (Group 2, 6 patients [12 eyes]). A complete
      ophthalmological examination including retinal nerve fiber layer (RNFL)
      evaluation by optical coherence tomography was provided for all patients before
      surgery and in the 1st week, 1st month, and 3rd month postoperatively. The 2
      groups were compared for quantitative changes in RNFL thickness and, thereby,
      resolution of papilledema. Statistical evaluation was performed using the Mann
      Whitney U-test with the aid of SPSS version 16.0. RESULTS: The mean preoperative
      RNFL thickness was 259.7 +/- 35.8 MUm in Group 1 and 244.5 +/- 53.4 MUm in Group
      2 (p = 0.798). The mean decrease in RNFL thickness was 101.3 +/- 38.8 MUm, 141.2
      +/- 34.6 MUm, and 162.0 +/- 35.9 MUm in Group 1 versus 97.0 +/- 44.6 MUm, 143 +/-
      45.6 MUm, and 130.0 +/- 59.8 MUm in Group 2 for the postoperative 1st week, 1st
      month, and 3rd month, respectively. There was no significant difference between
      the two groups with respect to decrease in RNFL thickness during the 1st week,
      1st month, and 3rd month (p = 0.563, p = 0.753, and p = 0.528, respectively).
      CONCLUSIONS: This is the first study to quantitatively evaluate papilledema in
      assessing the success of ETV and CSF shunting. The authors' results indicated
      that ETV is as effective as CSF shunting with respect to decreasing intracranial
      pressure and resolution of papilledema.

PMID- 24678780
TI  - Enhanced expression of proapoptotic and autophagic proteins involved in the cell
      death of glioblastoma induced by synthetic glycans.
AB  - OBJECT: Glioblastoma is the most aggressive malignant brain tumor, and overall
      patient survival has not been prolonged even by conventional therapies.
      Previously, the authors found that chemically synthesized glycans could be
      anticancer agents against growth of a series of cancer cells. In this study, the
      authors examined the effects of glycans on the growth of glioblastoma cells both
      in vitro and in vivo. METHODS: The authors investigated not only the occurrence
      of changes in the cell signaling molecules and expression levels of various
      proteins related to cell death, but also a mouse model involving the injection of
      glioblastoma cells following the administration of synthetic glycans. RESULTS:
      Synthetic glycans inhibited the growth of glioblastoma cells, induced the
      apoptosis of the cells with cleaved poly (adenosine diphosphate-ribose)
      polymerase (PARP) expression and DNA fragmentation, and also caused autophagy, as
      shown by the detection of autophagosome proteins and monodansylcadaverine
      staining. Furthermore, tumor growth in the in vivo mouse model was significantly
      inhibited. A dramatic induction of programmed cell death was found in
      glioblastoma cells after treatment with synthetic glycans. CONCLUSIONS: These
      results suggest that synthetic glycans could be a promising novel anticancer
      agent for performing chemotherapy against glioblastoma.

PMID- 24678781
TI  - Blunt traumatic occlusion of the internal carotid and vertebral arteries.
AB  - OBJECT: The stroke rate, management, and outcome after blunt cerebrovascular
      occlusion (Biffl Grade IV injury) is not well defined, given the rarity of the
      disease. Both hemodynamic failure and embolic mechanisms have been implicated in
      the pathophysiology of subsequent stroke after blunt cerebrovascular occlusion.
      In this study, the authors evaluated their center's experience with Biffl Grade
      IV injuries, focusing on elucidating the mechanisms of stroke and their optimal
      management. METHODS: A retrospective review identified all internal carotid
      artery (ICA) or vertebral artery (VA) Biffl Grade IV injuries over a 7-year
      period at a single institution. RESULTS: Fifty-nine Biffl Grade IV injuries were
      diagnosed affecting 11 ICAs, 44 unilateral VAs, and 2 bilateral VAs. The stroke
      rates were 64%, 9%, and 50%, respectively. Of the 11 Biffl Grade IV ICA injuries,
      5 presented with stroke while 2 developed delayed stroke. An ipsilateral
      posterior communicating artery greater than 1 mm on CT angiography was protective
      against stroke due to hemodynamic failure (p = 0.015). All patients with Biffl
      Grade IV injuries affecting the ICA who had at least 8 emboli per hour on
      transcranial Doppler (TCD) ultrasonography developed an embolic pattern of stroke
      (p = 0.006). Treatment with aspirin versus dual antiplatelet therapy had a
      similar effect on stroke rate in the ICA group (p = 0.5) and all patients who
      suffered stroke either died (n = 3) or required a decompressive hemicraniectomy
      with subsequent poor outcome (n = 4). All 10 strokes associated with Biffl Grade
      IV VA injuries were embolic and clinically asymptomatic. In VA Biffl Grade IV
      injury, neither the presence of emboli nor treatment with antiplatelet agents
      affected stroke rates. CONCLUSIONS: At the authors' institution, traumatic ICA
      occlusion is rare but associated with a high stroke rate. Robust collateral
      circulation may mitigate its severity. Embolic monitoring with TCD
      ultrasonography and prophylactic antiplatelet therapy should be used in all ICA
      Biffl Grade IV injuries. Unilateral VA Biffl Grade IV injury is the most common
      type of traumatic occlusion and is associated with significantly less morbidity.
      Embolic monitoring using TCD and prophylactic antiplatelet therapy do not appear
      to be beneficial in patients with traumatic VA occlusion.

PMID- 24678782
TI  - Endoscopic endonasal surgery for suprasellar meningiomas: experience with 75
      patients.
AB  - OBJECT: Following the introduction of the neurosurgical microscope, the outcomes
      in suprasellar meningioma surgery were dramatically improved. More recently, the
      neurosurgical endoscope has been introduced as a visualization option during
      removal of skull base tumors, both transcranially and endonasally. The authors
      retrospectively reviewed the effectiveness of endoscopic endonasal surgery (EES)
      in the management of suprasellar meningiomas. METHODS: Between 2002 and 2011, 75
      patients (81.3% female) with suprasellar meningiomas underwent EES at the
      University of Pittsburgh Medical Center. The authors present the results of EES
      and analyze the resection rates, visual outcome, and complications. RESULTS:
      Seventy-one patients presented with primary tumors, whereas 4 were previously
      treated elsewhere. Their mean age was 57.3 years (range 36-88 years), and most
      patients presented with visual loss (81.3%). Tumors occupied the tuberculum
      sellae (86.7%) and planum sphenoidale (50.7%), with extension into the optic
      canals in 26.7% (unilateral in 21.3% and bilateral in 5.3%) and the pituitary
      fossa (9.3%). Gross-total tumor resection (Simpson Grade I) was achieved in 76%
      of the cases in the whole cohort and in 81.4% of the patients in whom it was the
      goal of surgery. Tumor location and extension into the optic canals was not a
      limitation for total resection. Tumor size, configuration, and vascular
      encasement were significant factors that influenced the degree of resection (p <
      0.0001). Vision was improved or normalized in 85.7% of the cases. Visual
      deterioration following EES occurred in 2 patients (3.6%). Complications included
      postoperative CSF leaks (25.3% overall, 16.1% in recent years) resulting in
      meningitis in 4 cases. One patient had an intraoperative injury of the artery of
      Heubner resulting in associated neurological deficit. Another elderly patient
      died within 1 month after EES due to cerebral vasospasm and multisystem
      impairment. No patient developed postoperative cerebral contusions, hemorrhage,
      or seizures. During a mean follow-up period of 29 months (range 1-98 months), 4
      patients have shown recurrence, but only 1 required repeat EES. CONCLUSIONS: With
      the goal of gross-total tumor resection and visual improvement, EES can achieve
      very good results, (comparable to microscopic approaches) for the treatment of
      suprasellar meningiomas. Avoidance of brain and optic nerve retraction,
      preservation of the vascularization of the optic apparatus, and wide
      decompression of the optic canals are the main advantages of EES for the
      treatment of suprasellar meningiomas, while CSF leaks remain a disadvantage.

PMID- 24678783
TI  - Proceraside A, a new cardiac glycoside from the root barks of Calotropis procera
      with in vitro anticancer effects.
AB  - We have studied the ethyl acetate fraction of the methanolic extract of the root
      barks of Calotropis procera (Asclepiadaceae) from Egypt. Bioassay-directed
      fractionation and final purification of the extract resulted in the
      identification of a new cardenolide glycoside named proceraside A (1) together
      with two known compounds, frugoside (2) and calotropin (3). Their structures were
      elucidated by extensive NMR studies and mass spectrometric data. The in vitro
      cytotoxicity of the isolated compounds was evaluated against A549 non-small cell
      lung cancer, U373 glioblastoma and PC-3 prostate cancer cell lines. They showed
      potent activity against the tested cancer cell lines with IC50 ranging from 0.005
      to 0.3 MUg/mL. Cisplatin was used as positive control.

PMID- 24678784
TI  - Synthesis, crystal structure, anti-inflammatory and anti-hyperglycemic activities
      of novel 3,4-disubstituted 1,2,4-triazol-5(4H)-one derivatives.
AB  - A new series of 3,4-disubstituted 1,2,4-triazol-5(4H)-one 5a-r, bearing various
      methoxyphenyl, fluorophenyl, tolyl and phenyl groups, was synthesized by the
      dehydrocyclization of hydrazinecarboxamides 4a-r by refluxing in a 2 N sodium
      hydroxide solution. Hydrazinecarboxamides 4a-r was synthesized via the
      condensation of the corresponding aralkanoic acid hydrazides, 3a-g, with fluoro-,
      tolyl- and methoxyphenylisocyanates. The newly synthesized compounds (5a-r) were
      characterized by IR, (1)H NMR and (13)C NMR analyses. The structure of one
      compound 5a was determined by single crystal X-ray diffraction analysis. All of
      the synthesized compounds were screened for their anti-inflammatory and anti
      diabetic (alpha-glucosidase and alpha-amylase inhibition) activity to identify
      new drugs that might be useful in preventing damage related to diabetes and
      inflammation. Compounds 5j, 5k and 5m decrease the expression of type II collagen
      in a dose dependent manner; similarly 5l decrease the COX-2 expression of rabbit
      articular chondrocytes in a dose dependent manner possessing potent anti
      inflammatory potential while some of derivatives including 5c, 5e, 5g and 5h
      cause inflammation. Meanwhile, excellent alpha-glucosidase and moderate alpha
      amylase inhibitory profiles against carbohydrate modulating enzymes were
      demonstrated by compounds 5b, 5f, 5k and 5q compared to the reference standard
      acarbose, and compounds 5g, 5h, 5i, 5j, 5l and 5o exhibited moderate to low
      enzyme inhibition potential among the series.

PMID- 24678785
TI  - Novel selenosemicarbazone metal complexes exert anti-tumor effect via
      alternative, caspase-independent necroptotic cell death.
AB  - The synthesis and chemical characterization of the novel 2,6-diacetylpyridine
      bis(selenosemicarbazone) metal complexes of Zn(II), Cd(II) and Ni(II) were
      published previously. Here we report first evidence on anti-proliferative
      activity of the complexes and molecular patterns that underlie it. The complexes
      and the corresponding ligand are shown to be cytotoxic on the panel of nine,
      malignant and non-malignant cell lines, with the exception of Ni(II) complex that
      did not achieve IC50 value on any of the cell lines tested. Further experiments
      on the selected cell lines including A 549, MRC-5, EA.hy 926 and HeLa, have shown
      that the complexes posses unambiguous property of inducing necrosis in the cells
      treated for 6 hours, with the ligand and Zn(II) complex being the most active on
      all cell lines. On the contrary, only small portion of early apoptotic events was
      detected, under the same experimental condition. This was in complete concordance
      with the results obtained from Western blot analysis of the treated cells that
      showed no or slight increase of the protein amounts of two crucial apoptotic
      mediators: Cytochrome C and Caspase III. We propose the model, under which tested
      complexes induce necroptosis in treated cells, a recently described type of cell
      death with necrotic morphological features and acting via caspase independent
      pathway, and without elevated amounts of intracellular ROS. Endothelial EA.hy 926
      cells have proven to be extremely sensitive on the necrosis-inducing effect of
      the complexes, which could indicate potential anti-angiogenic effect of the novel
      complexes that is to be investigated.

PMID- 24678786
TI  - Apolipoprotein E gene variants of Alzheimer's disease and vascular dementia
      patients in a community population of Nanking.
AB  - To explore apolipoprotein E gene variants distribution among the patients of
      Alzheimer's disease and vascular dementia for the elderly community population in
      Nanking, the polymerase chain reaction and restriction fragment length
      polymorphism techniques were employed to analyze the gene frequency of
      apolipoprotein E (ApoE) for 113 cases with Alzheimer's disease (AD), 85 cases
      with vascular dementia (VaD), 147 cases with questionable dementia (QD), and 396
      dementia-free controls. It was found that ApoE epsilon4 gene container (37.17%)
      and allele frequency (21.24 +/- 2.72) of ApoE epsilon4 in AD group were
      significantly higher than those in both control and VaD group (p < 0.05). With
      the increment of epsilon4 gene dose, the incidence of the AD was significantly
      increased. Compared with the control group, ApoE epsilon4 had risk ratio (RR) of
      1.82 to develop AD (p = 4e-4), and attributable risk percentage (ARP) of 45%.
      These results suggest that ApoE epsilon4 gene may be responsible for up to 45% of
      the genetic component of Alzheimer's disease, and may act as a discriminator
      between AD and VaD as well.

PMID- 24678787
TI  - Experiences of self-management support from GPs among Australian ethnically
      diverse diabetes patients: a qualitative study.
AB  - Ethnically diverse diabetes patients face significant challenges in diabetes self
      management ranging from cultural expectations to inequalities in health care
      provision. This study explored the experiences of ethnically diverse patients
      with diabetes attending group diabetes education in receiving self-management
      support from GPs. An approach based on phenomenology was used to analyse
      participants' experiences in self-management support across three group
      interviews comprising 28 Australian ethnically diverse diabetes patients: Arabic
      speaking group (n = 11), English-speaking group (n = 9) and Vietnamese-speaking
      group (n = 8). Two themes emerged related to the poor quality of information to
      support self-management and challenges in negotiating traditional consultation
      styles. In particular, participants believed they knew more about diabetes self
      management than their GPs but felt unable to influence consultation style and
      communicate their changing needs in self-management support. The health care and
      information needs of ethnically diverse patients continue to be marginalised
      within health systems. This small exploratory study highlights the need for
      further research to illuminate interactions between ethnically diverse diabetes
      patients and GPs in supporting long-term diabetes self-management.

PMID- 24678788
TI  - Female sterilization: update on clinical efficacy, side effects and
      contraindications.
AB  - PURPOSE: The aim of this review is to compare studies concerning female
      sterilization in order to define the most suitable approach and device for each
      patient considering timing, safety, cost-effectiveness, failure rate,
      complication rate and patient satisfaction. METHODS: A systematic literature
      search was conducted in electronic databases MEDLINE-EMBASE-Sciencedirect and
      Cochrane Library between 2000 and 2012. All original descriptions, case reports,
      retrospective and review articles on tubal sterilization methods have been
      considered. Outcome measures were effectiveness, tolerability, procedure
      complications and female satisfaction. RESULTS: The ideal female sterilization
      system should be a simple, safe, highly efficient, easily learned, inexpensive,
      one-time procedure without negative side-effects. Nowadays, the trans-cervical
      approach is associated with minimal postoperative pain, allowing short
      hospitalization and fast resumption of daily activities. Laparoscopic and
      laparotomic approaches are considered second choices, since, particularly in
      developing countries, the transcervical hysteroscopic methods will increasingly
      spread within gynaecological clinical practice. CONCLUSIONS: Safety issues,
      hospital stay, costs and surgeons' experience are important factors in decision
      making of the method for female sterilization. Hysteroscopic devices should be
      preferred when possible. The counselling time remains a fundamental step in
      choice. The decision concerning method depends on the setting, the surgeon's
      experience, the country's economical development and the woman's preference.

PMID- 24678789
TI  - Learning curve for breast mass excision using a vacuum-assisted biopsy system.
AB  - BACKGROUND: Vacuum-assisted breast biopsy system (VAB) is an alternative modality
      to core needle biopsy for the diagnosis of breast lesions. MATERIAL AND METHODS:
      Fifty-four patients who underwent ultrasound-guided VAB procedures were analyzed.
      Patients were categorized into two groups: The first 20 consecutive patients as
      group A and the next 34 consecutive patients as group B. RESULTS: Fifty-two
      patients underwent excision, and two underwent biopsy only. Moving average curves
      showed a plateau phase for performing VAB procedures after the 20(th) patient.
      Total operation times of group B were significantly shorter than those of group A
      (p < 0.001). Complication rates in group B tended to be lower, and VAB probe
      position of group B tended to be better than that of group A, but these
      differences were not statistically significant. CONCLUSION: Our data suggest the
      existence of a learning curve for ultrasound-guided VAB procedures. VAB
      procedures can be performed safely, even during the early learning period.

PMID- 24678790
TI  - Intravitreal Ranibizumab for the Treatment of Irvine-Gass Syndrome.
AB  - PURPOSE: The purpose of our study was to evaluate the potential efficacy and
      safety of intravitreal ranibizumab in patients with pseudophakic cystoid macular
      edema (CME). METHODS: This retrospective study comprised 7 eyes with CME treated
      with intravitreal ranibizumab. Patients were examined at 1 week and 1 month after
      injection and monthly thereafter. Main outcome measures included changes in best
      corrected visual acuity (BCVA) and central retinal thickness (CRT). Safety was
      assessed by ophthalmic examination and report of systemic adverse effects.
      RESULTS: There was a statistically significant difference on BCVA (p < 0.001) and
      CRT (p < 0.001) before and after the ranibizumab injection. One injection
      appeared to be sufficient for the resolution of CME, while recurrence was
      observed in 1 patient, in a long-term follow-up. No observable ocular or systemic
      side effects were found. CONCLUSIONS: Intravitreal ranibizumab seems to be
      effective and safe for the treatment of pseudophakic CME, demonstrating a
      statistically significant difference in BCVA as well as CRT.

PMID- 24678791
TI  - Ocular Manifestations of X-linked Chronic Granulomatous Disease: About Two
      Atypical Case Reports.
AB  - PURPOSE: Two atypical cases of ocular localizations of chronic granulomatous
      disease are reported. METHODS: The first case is about a 22-year-old woman
      carrier of the disease who developed active intraocular inflammation and
      choroidal granulomas successfully treated by steroids. The second is about a 2
      year-old boy consulting for unilateral anterior uveitis and subsequent anterior
      chamber granuloma development as first signs of the disease. RESULTS: X-linked
      chronic granulomatous disease is a rare inherited primary immunodeficiency
      syndrome characterized by disorders of phagocytic cells resulting in recurrent
      infections and development of granulomas. Ophthalmological manifestations are not
      rare and are mainly represented by surface and intraocular inflammation with
      possible choroidal granulomas. The two cases reported here are atypical, one of
      active inflammation in a carrier and the other revealing the disease. CONCLUSION:
      Ophthalmologists must be aware of chronic granulomatous disease and the possible
      ocular involvement of this disorder.

PMID- 24678792
TI  - Complexation of amyloid fibrils with charged conjugated polymers.
AB  - It has been suggested that conjugated charged polymers are amyloid imaging agents
      and promising therapeutic candidates for neurological disorders. However, very
      less is known about their efficacy in modulating the amyloid aggregation pathway.
      Here, we studied the modulation of Parkinson's disease associated alpha-synuclein
      (AS) amyloid assembly kinetics using conjugated polyfluorene polymers (PF,
      cationic; PFS, anionic). We also explored the complexation of these charged
      polymers with the various AS aggregated species including amyloid fibrils and
      oligomers using multidisciplinary biophysical techniques. Our data suggests that
      both polymers irrespective of their different charges in the side chains increase
      the fibrilization kinetics of AS and also remarkably change the morphology of the
      resultant amyloid fibrils. Both polymers were incorporated/aligned onto the AS
      amyloid fibrils as evident from electron microscopy (EM) and atomic force
      microscopy (AFM), and the resultant complexes were structurally distinct from
      their pristine form of both polymers and AS supported by FTIR study.
      Additionally, we observed that the mechanism of interactions between the polymers
      with different species of AS aggregates were markedly different. 

PMID- 24678793
TI  - The reliability of a severity rating scale to measure stuttering in an unfamiliar
      language.
AB  - With increasing multiculturalism, speech-language pathologists (SLPs) are likely
      to work with stuttering clients from linguistic backgrounds that differ from
      their own. No research to date has estimated SLPs' reliability when measuring
      severity of stuttering in an unfamiliar language. Therefore, this study was
      undertaken to estimate the reliability of SLPs' use of a 9-point severity rating
      (SR) scale, to measure severity of stuttering in a language that was different
      from their own. Twenty-six Australian SLPs rated 20 speech samples (10 Australian
      English [AE] and 10 Mandarin) of adults who stutter using a 9-point SR scale on
      two separate occasions. Judges showed poor agreement when using the scale to
      measure stuttering in Mandarin samples. Results also indicated that 50% of
      individual judges were unable to reliably measure the severity of stuttering in
      AE. The results highlight the need for (a) SLPs to develop intra- and inter-judge
      agreement when using the 9-point SR scale to measure severity of stuttering in
      their native language (in this case AE) and in unfamiliar languages; and (b)
      research into the development and evaluation of practice and/or training packages
      to assist SLPs to do so.

PMID- 24678794
TI  - GaAs/AlGaAs nanowire photodetector.
AB  - We demonstrate an efficient core-shell GaAs/AlGaAs nanowire photodetector
      operating at room temperature. The design of this nanoscale detector is based on
      a type-I heterostructure combined with a metal-semiconductor-metal (MSM) radial
      architecture, in which built-in electric fields at the semiconductor
      heterointerface and at the metal/semiconductor Schottky contact promote
      photogenerated charge separation, enhancing photosensitivity. The spectral
      photoconductive response shows that the nanowire supports resonant optical modes
      in the near-infrared region, which lead to large photocurrent density in
      agreement with the predictions of electromagnetic and transport computational
      models. The single nanowire photodetector shows a remarkable peak
      photoresponsivity of 0.57 A/W, comparable to large-area planar GaAs
      photodetectors on the market, and a high detectivity of 7.2 * 10(10) cm.Hz(1/2)/W
      at lambda = 855 nm. This is promising for the design of a new generation of
      highly sensitive single nanowire photodetectors by controlling the optical mode
      confinement, bandgap, density of states, and electrode engineering. 

PMID- 24678795
TI  - Identification of critical phosphorylation sites on the carboxy tail of
      melanopsin.
AB  - Light-activated opsins undergo carboxy-terminal phosphorylation, which
      contributes to the deactivation of their photoresponse. The photopigment
      melanopsin possesses an unusually long carboxy tail containing 37 serine and
      threonine sites that are potential sites for phosphorylation by a G-protein
      dependent kinase (GRK). Here, we show that a small cluster of six to seven sites
      is sufficient for deactivation of light-activated mouse melanopsin. Surprisingly,
      these sites are distinct from those that regulate deactivation of rhodopsin. In
      zebrafish, there are five different melanopsin genes that encode proteins with
      distinct carboxy-terminal domains. Naturally occurring changes in the same
      cluster of phosphorylatable amino acids provides diversity in the deactivation
      kinetics of the zebrafish proteins. These results suggest that variation in
      phosphorylation sites provides flexibility in the duration and kinetics of
      melanopsin-mediated light responses.

PMID- 24678796
TI  - Mortality from cancers of the extra-thoracic airways in relation to radon progeny
      in the Wismut cohort, 1946-2008.
AB  - PURPOSE: Inhalation of radon progeny can cause high lung and respiratory tract
      radiation doses. The aim of this paper was to examine the relationship between
      radon progeny and cancers of the extra-thoracic airways in the German uranium
      miner cohort for an extended follow-up through 2008. METHODS: The cohort included
      58,690 workers employed between 1946 and 1989 at the Wismut company. Exposure to
      radon progeny in Working Level Months (WLM) was determined from a comprehensive
      job-exposure matrix. The mean (max) cumulative exposure to radon among exposed
      cohort members (86%) was 280 WLM (3,224 WLM). Internal Poisson regression models
      were applied to estimate the linear Excess Relative Risk (ERR) per unit of
      cumulative exposure to radon. RESULTS: A small increase in the mortality from all
      cancers of the extra-thoracic airways combined with increasing cumulative
      exposure to radon was found (ERR/100 WLM = 0.036, p = 0.12), based on 234 deaths.
      The estimated ERR per 100 WLM for relevant cancer sub-groups were: 0.017 (p >
      0.5) larynx (n = 94); 0.077 (p = 0.20) pharynx (n = 74); and 0.030 (p > 0.5)
      tongue and mouth (n = 55). CONCLUSION: RESULTS indicated a small but not
      statistically significant increase in mortality from cancers of the extra
      thoracic airways in relation to radon. Low statistical power and uncontrolled
      confounding were limitations of this study.

PMID- 24678797
TI  - Retrospective estimation of Plutonium-239 doses from transfer to the fetus for
      Mayak PA workers.
AB  - PURPOSE: The estimation of plutonium fetal transfer and the calculation of
      individual in utero and postnatal doses for the Mayak Production Association (PA)
      offspring cohort. MATERIALS AND METHODS: The model developed by the International
      Commission on Radiological Protection (ICRP) for the transfer of plutonium to the
      fetus following maternal intakes before and during pregnancy has been adjusted
      for application to analysis of the fetal transfer of (239)Pu for Mayak workers.
      Improved estimates of fetal to maternal concentration ratios (CF:CM) have been
      obtained based on a correlation observed between adult offsprings' measured daily
      urine (239)Pu activity and estimates of their mothers' systemic activity at
      conception. Data on (239)Pu activity in daily urine samples were collected from
      13 selected adults whose mothers worked at the Mayak PA facility during the
      period from 1948-1953, before and/or during pregnancy. RESULTS: A comparison of
      measured and modeled excretion data enabled a mean value of 0.18 +/- 0.02 (n =
      21) to be inferred for the Pu CF:CM ratio, with a coefficient of variation of
      60%. CONCLUSIONS: Point estimates of the individual in utero and postnatal
      absorbed doses for the red bone marrow and liver were in the range 2...13 mGy in
      95% of the cases for the cohort of 1936 offspring.

PMID- 24678798
TI  - Mechanistic aspects of the radiation-chemical reduction of graphene oxide to
      graphene-like materials.
AB  - PURPOSE: The aim of the work was to investigate mechanistic details of the
      preparation of graphene-like materials (GLM) via reduction of graphene oxide (GO)
      in aqueous dispersions by electron beam (EB) generated reducing free radicals.
      MATERIALS AND METHODS: A 10 MeV linear accelerator was employed to irradiate
      aqueous GO dispersions at ambient temperatures. The kinetics of GO reduction was
      followed using UV-Vis spectroscopy. The resulting GLM were characterized by X-ray
      photoelectron spectroscopy (XPS), Transmission electron microscopy (TEM), Raman
      spectroscopy and conductivity measurements. RESULTS: The reduction of GO could be
      afforded with high efficiency within minutes at room temperature via the reaction
      of GO with reducing radicals generated by EB irradiation. The detailed
      investigation of the reduction mechanism allowed a selection of the best reducing
      free radicals in terms of both their efficiency and environmental impact of their
      precursors and final products. CONCLUSIONS: The EB-treatment of aqueous GO
      dispersions is a highly efficient, environmentally friendly, cost-effective and
      easily up-scalable method for the preparation of GLM. The efficiency of the new
      reduction approach is comparable with the best existing methods.

PMID- 24678799
TI  - Autophagy: detection, regulation and its role in cancer and therapy response.
AB  - PURPOSE: Macroautophagy is a catabolic pathway that degrades cellular components
      through the lysosomal machinery. Cytoplasmic components are sequestered in double
      membrane autophagosomes. They fuse with lysosomes where their cargo is delivered
      for degradation and recycling. Autophagy acts as a survival mechanism under
      stress by producing energy and as an intracellular quality management system by
      clearing damaged organelles like mitochondria and proteins. In this review, the
      regulation and the role of autophagy in cancer and therapy response are
      discussed. Furthermore, we will summarize methods for detecting autophagy in
      vitro and in vivo. CONCLUSION: During the early and late stages of cancer
      development, the role of autophagy differs. In the very early stages of
      carcinogenesis, autophagy has an important function by reducing cancer initiating
      genetic instability and aberrant protein aggregates as well as promoting anti
      cancer immune response. In established malignant tumors autophagy confers
      resistance against metabolic stress caused by nutrient deprivation and the rapid
      proliferation of carcinoma cells. This function of autophagy is also important
      for radiation and chemotherapy resistance in cancer. Our laboratory has found
      that Neuropilin-2-induced autophagy is a potent mediator of therapy resistance in
      different cancer types. Autophagy not only promotes the survival of tumor cells,
      but also leads to autophagic cell death. During dysfunctional apoptosis this form
      of cell death mainly sensitizes cancer cells for therapy such as ionizing
      radiation. Therefore, the functions of autophagy during cancer progression and
      therapy are two-sided and further research is needed to understand these in more
      detail.

PMID- 24678800
TI  - New technology for separating resin powder and fiberglass powder from fiberglass
      resin powder of waste printed circuit boards.
AB  - New recycling technologies have been developed lately to enhance the value of the
      fiberglass powder-resin powder fraction (FRP) from waste printed circuit boards.
      The definite aim of the present paper is to present some novel methods that use
      the image forces for the separation of the resin powder and fiberglass powder
      generated from FRP during the corona electrostatic separating process. The
      particle shape charactization and particle trajectory simulation were performed
      on samples of mixed non-metallic particles. The simulation results pointed out
      that particles of resin powder and particles of fiberglass powder had different
      detach trajectories at the conditions of the same size and certain device
      parameters. An experiment carried out using a corona electrostatic separator
      validated the possibility of sorting these particles based on the differences in
      their shape characteristics. The differences in the physical properties of the
      different types of particles provided the technical basis for the development of
      electrostatic separation technologies for the recycling industry. 

PMID- 24678801
TI  - Reductions in expression of growth regulating genes in skeletal muscle with age
      in wild type and myostatin null mice.
AB  - BACKGROUND: Genes that decline in expression with age and are thought to
      coordinate growth cessation have been identified in various organs, but their
      expression in skeletal muscle is unknown. Therefore, our objective was to
      determine expression of these genes (Ezh2, Gpc3, Mdk, Mest, Mycn, Peg3, and
      Plagl1) in skeletal muscle from birth to maturity. We hypothesized that
      expression of these genes would decline with age in skeletal muscle but differ
      between sexes and between wild type and myostatin null mice. RESULTS: Female and
      male wild type and myostatin null mice (C57BL/6J background) were sacrificed by
      carbon dioxide asphyxiation followed by decapitation at d -7, 0, 21, 42, and 70
      days of age. Whole bodies at d -7, all muscles from both hind limbs at d 0, and
      bicep femoris muscle from d 21, 42 and 70 were collected. Gene expression was
      determined by quantitative real-time PCR. In general, expression of these growth
      regulating genes was reduced at d 21 compared with day 0 and d -7. Expression of
      Gpc3, Mest, and Peg3 was further reduced at d 42 and 70 compared with d 21,
      however the expression of Mycn increased from d 21 to d 42 and 70. Myostatin null
      mice, as expected, were heavier with increased biceps femoris weight at d 70.
      However, with respect to sex and genotype, there were few differences in
      expression. Expression of Ezh2 was increased at d 70 and expression of Mdk was
      increased at d 21 in myostatin null mice compared with wild type, but no other
      genotype effects were present. Expression of Mdk was increased in females
      compared to males at d 70, but no other sex effects were present. CONCLUSIONS:
      Overall, these data suggest the downregulation of these growth-regulating genes
      with age might play a role in the coordinated cessation of muscle growth similar
      to organ growth but likely have a limited role in the differences between sexes
      or genotypes.

PMID- 24678802
TI  - Somatosensory perception of running shoe mass.
AB  - Running shoes are often marketed based on mass. A total of 50 young adult males
      participated across two separate experiments to determine how well they could
      perceive the relative masses of five different running shoes using hands versus
      feet. For the foot portion, subjects were blindly fitted with the shoes and asked
      to rank their masses individually using visual analogue scales (VAS) and verbal
      rankings. For the hand portion, two different methods were used, one presenting
      all shoes simultaneously and the other presenting the shoes individually. Verbal
      accuracy and VAS scores correlated across subjects for the hand and foot, but
      accuracy in mass perception by the feet was 30% compared to 92% or 63% by the
      hand (depending on the method). These results indicate the foot perceives mass
      poorly compared to the hand, and that consumers' perception of shoe mass may come
      more from handling shoes versus wearing them. 

PMID- 24678803
TI  - Structural characterization of methylenedianiline regioisomers by ion mobility
      mass spectrometry, tandem mass spectrometry, and computational strategies: I.
      Electrospray spectra of 2-ring isomers.
AB  - Purified methylenedianiline (MDA) regioisomers were structurally characterized
      and differentiated using tandem mass spectrometry (MS/MS), ion mobility-mass
      spectrometry (IM-MS), and IM-MS/MS in conjunction with computational methods. It
      was determined that protonation sites on the isomers can vary depending on the
      position of amino groups, and the resulting protonation sites play a role in the
      gas-phase stability of the isomer. We also observed differences in the relative
      distributions of protonated conformations depending on experimental conditions
      and instrumentation, which is consistent with previous studies on aniline in the
      gas phase. This work demonstrates the utility of a multifaceted approach for the
      study of isobaric species and elucidates why previous MDA studies may have been
      unable to detect and/or differentiate certain isomers. Such analysis may prove
      useful in the characterization of larger MDA multimeric species, industrial MDA
      mixtures, and methylene diphenyl diisocyanate (MDI) mixtures used in polyurethane
      synthesis. 

PMID- 24678804
TI  - A quasi-experimental study of the effects of an integrated care intervention for
      the frail elderly on informal caregivers' satisfaction with care and support.
AB  - BACKGROUND: This study explored the effects of an integrated care model for the
      frail elderly on informal caregivers' satisfaction with care and support
      services. METHODS: A 62-item instrument was developed and deployed in an
      evaluative before/after study using a quasi-experimental design and enrolling a
      control group. The definitive study population (n=63) consisted mainly of female
      informal caregivers who did not live with the care recipient. Analysis of
      separate items involved group comparisons, using paired and unpaired tests, and
      regression analyses, with baseline measurements, control variables (sex, age and
      living together with care recipient) and the intervention as independent
      variables. Subsequently, the underlying factor structure of the theoretical
      dimensions was investigated using primary component analysis. Group comparisons
      and regression analyses were performed on the resulting scales. RESULTS:
      Satisfaction with the degree to which care was provided according to the need for
      care of the recipients increased, while satisfaction with the degree to which
      professionals provided help with administrative tasks, the understandability of
      the information provided and the degree to which informal caregivers knew which
      professionals to call, decreased. Primary component analysis yielded 6 scales for
      satisfaction with care and 5 scales for satisfaction with caregiver support, with
      sufficient reliability. CONCLUSIONS: The results suggest that expectations
      regarding the effects of integrated care on informal caregiver satisfaction may
      not be realistic. However, the results must be seen in light of the small sample
      size and should therefore be considered as preliminary. Nonetheless, this study
      provides guidance for further research and integrated care interventions
      involving informal caregivers. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN05748494. Date of registration: 14/03/2013.

PMID- 24678805
TI  - Per-O-acetylation of cellulose in dimethyl sulfoxide with catalyzed
      transesterification.
AB  - Cellulose acetylation was investigated in dimethyl sulfoxide (DMSO) with
      isopropenyl acetate (IPA) as acetylating reagent and 1,8-diazabicyclo[5,4,0]undec
      7-ene (DBU) as catalyst at 70-130  degrees C for 3-12 h. The degree of
      substitution (DS) of acetylated cellulose was comparatively determined by
      titration and 1H NMR and confirmed by FT-IR analysis. The results indicated that
      per-O-acetylation was achieved at >90  degrees C for a relatively long duration.
      The three well-resolved peaks of carbonyl carbons in 13C NMR spectra also
      provided evidence of per-O-acetylation. The solubility of cellulose acetates in
      common organic solvents was examined, and the result showed that chloroform can
      be an alternative choice as a solvent for fully acetylated cellulose formed in
      this study besides DMSO. The intrinsic viscosity of acetylated cellulose solution
      implied almost no degradation of cellulose during acetylation in DMSO except at
      higher temperature (130  degrees C) for a long time.

PMID- 24678806
TI  - Influence of delivery characteristics and socioeconomic status on giving birth by
      caesarean section - a cross sectional study during 2000-2010 in Finland.
AB  - BACKGROUND: Caesarean section (CS) rates especially without medical indication
      are rising worldwide. Most of indications for CS are relative and CS rates for
      various indications vary widely. There is an increasing tendency to perform CSs
      without medical indication on maternal request. Women with higher socioeconomic
      status (SES) are more likely to give birth by CS. We aimed to study whether
      giving birth by CS was associated with SES and other characteristics among
      singleton births during 2000-2010 in Finland with publicly funded health care.
      METHODS: Data were gathered from the Finnish Medical Birth Register. The
      likelihood of giving birth by CS according to CS type (planned and non-planned),
      parity (nulliparous vs. multiparous), socio-demographic factors, delivery
      characteristics and time periods (2000-2003, 2004-2007 and 2008-2010) was
      determined by using logistic regression analysis. SES was classified as upper
      white collar workers (highest SES), lower white collar workers, blue collar
      workers (lowest SES), others (all unclassifiable cases) and cases with missing
      information. RESULTS: In total, 19.8% (51,511 of 259,736) of the nulliparous
      women and 13.1% (47,271 of 360,727) of the multiparous women gave birth by CS. CS
      was associated with several delivery characteristics, such as placental
      abruption, placenta previa, birth weight and fear of childbirth, among both
      parity groups. After adjustment, the likelihood of giving birth by planned CS was
      reduced by 40% in nulliparous and 55% in multiparous women from 2000-2003 to 2008
      2010, whereas the likelihood of non-planned CSs did not change. Giving birth by
      planned and non-planned CS was up to 9% higher in nulliparous women and up to 17%
      higher in multiparous women in the lowest SES groups compared to the highest SES
      group. CONCLUSIONS: Giving birth by CS varied by clinical indications. Women with
      the lowest SES were more likely to give birth by CS, indicating that the known
      social disparity in pregnancy complications increases the need for operative
      deliveries in these women. Overall, the CS policy in Finland shows favoring a
      trial of labor over planned CS and reflects no inequity in healthcare services.

PMID- 24678807
TI  - The efficacy and safety of arotinolol combined with a different calcium channel
      blocker in the treatment of Chinese patients with essential hypertension: a one
      year follow-up study.
AB  - BACKGROUND: Combined treatment of a calcium antagonist and alpha/beta
      adrenoreceptor blocker is expected to offer some advantages in the management of
      hypertension; however, their antihypertensive efficacy and safety remain
      relatively under-explored. METHODS: The current study addresses the 24-h
      antihypertensive efficacy and safety of arotinolol combined with a different
      calcium channel blocker. One-hundred fifty-two patients were randomly divided
      into three groups: nifedipine, amlodipine and felodipine group. In each group,
      the antihypertensive treatment dose was 30 mg/d, 5 mg/d, 5 mg/d long acting
      nifedipine, amlodipine, felodipine plus 20 mg/d arotinolol, respectively. Blood
      pressure was measured in ABPM devices and mercury manometer. RESULTS: The result
      showed that the effective rate of one year antihypertensive treatment of
      arotinolol combined with nifedipine was 51 of 53, significantly effective (p <
      0.05) among three combinations. It also showed that there was no statistical
      significant difference (p > 0.05) in controlled rate of morning peak blood
      pressure between treatment of arotinolol combined with amlodipine and arotinolol
      combined with nifedipine, but there was a significant difference (p < 0.01) in
      controlled rate of morning peak blood pressure between arotinolol combined with
      nifedipine vs. felodipine and arotinolol combined with amlodipine vs. felodipine.
      CONCLUSIONS: The therapy approached of arotinolol combined with nifedipine or
      amlodipine could be effective and well-tolerated, and they can be used as the
      better chosen antihypertensive drug.

PMID- 24678808
TI  - Postpartum breast involution reveals regression of secretory lobules mediated by
      tissue-remodeling.
AB  - INTRODUCTION: A postpartum diagnosis of breast cancer is an independent predictor
      of metastases, however the reason is unknown. In rodents, the window of
      postpartum mammary gland involution promotes tumor progression, suggesting a role
      for breast involution in the poor prognosis of human postpartum breast cancers.
      Rodent mammary gland involution is characterized by the programmed elimination of
      the secretory lobules laid down in preparation for lactation. This tissue
      involution process involves massive epithelial cell death, stromal remodeling,
      and immune cell infiltration with similarities to microenvironments present
      during wound healing and tumor progression. Here, we characterize breast tissue
      from premenopausal women with known reproductive histories to determine the
      extent, duration and cellular mechanisms of postpartum lobular involution in
      women. METHODS: Adjacent normal breast tissues from premenopausal women (n = 183)
      aged 20 to 45 years, grouped by reproductive categories of nulliparous, pregnant
      and lactating, and by time since last delivery were evaluated histologically and
      by special stain for lobular area, lobular type composition, apoptosis and immune
      cell infiltration using computer assisted quantitative methods. RESULTS: Human
      nulliparous glands were composed dominantly of small (approximately 10 acini per
      lobule) and medium (approximately 35 acini per lobule) sized lobules. With
      pregnancy and lactation, a >10 fold increase in breast epithelial area was
      observed compared to nulliparous cases, and lactating glands were dominated by
      mature lobules (>100 acini per lobule) with secretory morphology. Significant
      losses in mammary epithelial area and mature lobule phenotypes were observed
      within 12 months postpartum. By 18 months postpartum, lobular area content and
      lobule composition were indistinguishable from nulliparous cases, data consistent
      with postpartum involution facilitating regression of the secretory lobules
      developed in preparation for lactation. Analyses of apoptosis and immune cell
      infiltrate confirmed that human postpartum breast involution is characterized by
      wound healing-like tissue remodeling programs that occur within a narrowed time
      frame. CONCLUSIONS: Human postpartum breast involution is a dominant tissue
      remodeling process that returns the total lobular area of the gland to a level
      essentially indistinguishable from the nulliparous gland. Further research is
      warranted to determine whether the normal physiologic process of postpartum
      involution contributes to the poor prognosis of postpartum breast cancer.

PMID- 24678809
TI  - Echocardiographic follow-up of patients with systemic sclerosis by 2D speckle
      tracking echocardiography of the left ventricle.
AB  - BACKGROUND: Subclinical myocardial involvement is common in systemic sclerosis
      (SSc) and associated with poor prognosis. Early detection, particularly during
      follow-up, is important. Two-dimensional speckle tracking echocardiography (STE)
      has already been shown to detect early left ventricular systolic impairment in
      SSc patients with advanced disease. The aim of this study was to assess the
      ability of STE to diagnose changes in left ventricular function in patients with
      SSc with preserved LV ejection fraction (LVEF) and normal pulmonary pressure over
      time. METHODS: This single-center pilot study included nineteen SSc patients
      without pulmonary hypertension and preserved LVEF (55.2 +/- 10.8 years, 13 women,
      mean modified Rodnan Skin Score of 8.2 +/- 6.5, median disease duration 6 +/- 4.5
      years). We performed STE at baseline and after two years (mean 756.6 +/- 8.8
      days). Pulmonary hypertension was ruled out in all patients by right heart
      catheterization (average mean PAP 17.7 +/- 3.5 mmHg). RESULTS: The LVEF remained
      unchanged (63.3 +/- 4.2% vs. 63.2 +/- 5.0%, P = ns), but the global longitudinal
      peak systolic strain of the left ventricle was significantly lower: baseline 
      22.0 +/- 2.3% vs. follow-up -20.8 +/- 2.1% (P = 0.04). The regional analysis
      showed a heterogeneous distribution of segmental systolic dysfunction that did
      not match any particular coronary artery distribution. In contrast, the LV
      diastolic function remained stable during follow-up. CONCLUSION: STE might be a
      sensititive and valuable method to detect early LV systolic impairment in
      patients with SSc and preserved LVEF during two years. Prospective evaluations
      are needed for prognostic implications of these changes.

PMID- 24678811
TI  - In vivo antimalarial efficacy of acetogenins, alkaloids and flavonoids enriched
      fractions from Annona crassiflora Mart.
AB  - Annona crassiflora and Annonaceae plants are known to be used to treat malaria by
      traditional healers. In this work, the antimalarial efficacy of different
      fractions of A. crassiflora, particularly acetogenin, alkaloids and flavonoid
      rich fractions, was determined in vivo using Plasmodium berghei-infected mice
      model and toxicity was accessed by brine shrimp assay. The A. crassiflora
      fractions were administered at doses of 12.5 mg/kg/day in a 4-day test protocol.
      The results showed that some fractions from woods were rich in acetogenins,
      alkaloids and terpenes, and other fractions from leaves were rich in alkaloids
      and flavonoids. The parasitaemia was significantly (p < 0.05, p < 0.001) reduced
      (57-75%) with flavonoid and alkaloid-rich leaf fractions, which also increased
      mean survival time of mice after treatment. Our results confirm the usage of this
      plant in folk medicine as an antimalarial remedy.

PMID- 24678812
TI  - The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases.
AB  - Chemokines are small proteins that control several tissue functions, including
      cell recruitment and activation under homeostatic and inflammatory conditions.
      CXCL8 (interleukin-8) is a member of the chemokine family that acts on CXCR1 and
      CXCR2 receptors. CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL7 are also ELR+
      chemokine members that bind to these receptors, especially CXCR2. The majority of
      studies on the biology of CXCL8 and their receptors have been performed in
      polymorphonuclear leukocytes. However, many other cells express CXCR1/CXCR2,
      including epithelial, endothelial, fibroblasts and neurons, contributing to the
      biological effects of CXCL8. There is substantial amount of experimental data
      suggesting that CXCL8 and receptors contribute to elimination of pathogens, but
      may also contribute significantly to disease-associated processes, including
      tissue injury, fibrosis, angiogenesis and tumorigenesis. Here, we discuss the
      biology of CXCL8 family and the potential therapeutic use of antagonists or
      blockers of these molecules in the context of organ-specific diseases.

PMID- 24678810
TI  - Characterization of the transcriptome and temperature-induced differential gene
      expression in QPX, the thraustochytrid parasite of hard clams.
AB  - BACKGROUND: The hard clam or northern quahog, Mercenaria mercenaria, is one of
      the most valuable seafood products in the United States representing the first
      marine resource in some Northeastern states. Severe episodes of hard clam
      mortality have been consistently associated with infections caused by a
      thraustochytrid parasite called Quahog Parasite Unknown (QPX). QPX is considered
      as a cold/temperate water organism since the disease occurs only in the coastal
      waters of the northwestern Atlantic Ocean from Maritime Canada to Virginia. High
      disease development at cold temperatures was also confirmed in laboratory studies
      and is thought to be caused predominantly by immunosuppression of the clam host
      even though the effect of temperature on QPX virulence has not been fully
      investigated. In this study, the QPX transcriptome was sequenced using Roche 454
      technology to better characterize this microbe and initiate research on the
      molecular basis of QPX virulence towards hard clams. RESULTS: Close to 18,000
      transcriptomic sequences were generated and functionally annotated. Results
      revealed a wide array of QPX putative virulence factors including a variety of
      peptidases, antioxidant enzymes, and proteins involved in extracellular mucus
      production and other secretory proteins potentially involved in interactions with
      the clam host. Furthermore, a 15 K oligonucleotide array was constructed and used
      to investigate the effect of temperature on QPX fitness and virulence factors.
      Results identified a set of QPX molecular chaperones that could explain its
      adaptation to cold temperatures. Finally, several virulence-related factors were
      up-regulated at low temperature providing molecular targets for further
      investigations of increased QPX pathogenicity in cold water conditions.
      CONCLUSIONS: This is one of the first studies to characterize the transcriptome
      of a parasitic labyrinthulid, offering new insights into the molecular bases of
      the pathogenicity of members of this group. Results from the oligoarray study
      demonstrated the ability of QPX to cope with a wide range of environmental
      temperatures, including those considered to be suboptimal for clam immunity (low
      temperature) providing a mechanistic scenario for disease distribution in the
      field and for high disease prevalence and intensity at low temperature. These
      results will serve as basis for studies aimed at a better characterization of
      specific putative virulence factors.

PMID- 24678813
TI  - Experience with a gonadotrophin-releasing hormone agonist prior to myomectomy-
      comparison of twice- vs thrice-monthly doses and a control group.
AB  - The aim of this randomised prospective study was to investigate the impact of
      preoperative gonadotrophin-releasing hormone agonist (GnRHa) compared with a
      control group with myomectomy. A total of 36 women (n = 36, group 1) with
      fibroids were randomised to receive either two monthly doses (n = 18/36, group
      1a) or three monthly doses of goserelin (n = 18/36, group 1b) prior to
      myomectomy. The 32 women who received no treatment (group 2) comprised the
      controls. All patients had similar demographic features. There were no
      significant differences among the three groups with respect to: (1) mean
      intraoperative blood loss; (2) preoperative and postoperative blood transfusion
      or (3) length of hospital stay. The only advantage of administering GnRHa prior
      to myomectomy for symptomatic fibroids in our population was a higher haemoglobin
      level prior to surgery among the women who received three doses of the drug.

PMID- 24678814
TI  - The fetal safety of cetirizine: an observational cohort study and meta-analysis.
AB  - Cetirizine, a second-generation antihistamine, is an active metabolite of
      hydroxyzine used in the treatment of allergies, but the data on fetal safety are
      inconclusive. Pregnant women who were counselled by the 'Motherisk Program'
      regarding cetirizine exposure were enrolled in a cohort study and compared with
      pregnant women counselled for non-teratogenic exposures. The objective was to
      measure the rate of adverse pregnancy outcomes. Subsequently, we also conducted a
      meta-analysis of cohort studies that examined the pregnancy outcomes of women
      exposed to hydroxyzine or cetirizine during pregnancy. In the cohort study, there
      were no significant differences in the rates of major malformations between the
      cetirizine exposed and comparison group. In the meta-analysis, cetirizine was not
      associated with increased teratogenic risk. In contrast, a meta-analysis of
      cetirizine and hydroxyzine studies showed a marginal association with major
      malformations. Cetirizine is not associated with a clinically important increase
      in risk of adverse fetal outcomes.

PMID- 24678815
TI  - Maximum bladder volume as surrogate screening test for detrusor overactivity.
AB  - Maximum bladder volume could be a simple surrogate measure to screen for detrusor
      overactivity (DO) which manifests with a frequency and small volume voids.
      Urodynamic traces from 577 women were reviewed. Maximum bladder volume was
      obtained from bladder diary. The urodynamic traces were reviewed for data and
      were categorised as normal, urodynamic stress incontinence, mixed incontinence
      and DO. The urodynamic data and maximum voided volume were compared between
      different categories and Receiver operating characteristic (ROC) curves were
      constructed. The median value for maximum-voided volume for women with DO was not
      significantly different from the other categories, whereas significant
      differences were found for the median values for urodynamic variables. ROC curves
      demonstrated extremely poor sensitivity and specificity for recorded maximum
      bladder volume and for urodynamic variables. The maximum-voided volume recorded
      on a three-day bladder diary is not discriminatory as a screening test for DO.

PMID- 24678816
TI  - Complications and pregnancy outcome following uterine compression suture for
      postpartum haemorrhage: a single centre experience.
AB  - In the treatment of postpartum haemorrhage from uterine atony, uterine
      compression sutures, such as the B-Lynch suture and its modifications have a role
      with the advantage of preservation of the uterus for fertility. There is however,
      a risk that apposition of the anterior and posterior walls of the uterus will
      impede drainage of lochia, resulting in undesirable complications. We undertook a
      five-year retrospective study of all women who underwent uterine compression
      sutures at the KK Women's and Children's Hospital, between 2008 and 2012. In
      total, 23 women had uterine compression sutures during the study period, of
      which, nineteen women managed to conserve their uterus. Our complication rate was
      25%, which included persistent vaginal discharge, pyometra and endometritis.
      There were three conceptions, with two successful pregnancies. Our study shows
      uterine compression suture to be a safe and effective alternative to avoid
      hysterectomy with preservation of fertility at the time of major postpartum
      haemorrhage. The outcome of subsequent pregnancies is reassuring.

PMID- 24678817
TI  - Chromosome abnormality incidence in fetuses with cerebral ventriculomegaly.
AB  - Ventriculomegaly (VM) is a marker of aneuploidy and warrants a detailed
      examination of fetal anatomy. Chromosomal abnormalities worsen the fetal and
      neonatal prognosis significantly and karyotyping of fetuses is critically
      important when accompanying anomalies are detected. Here, we report the genetic
      results of 140 fetuses with isolated and non-isolated VM detected during a second
      trimester ultrasound examination followed by invasive in utero diagnostic
      procedures for karyotyping. VM was diagnosed in seven (5%) fetuses with abnormal
      karyotype and the chromosomal abnormality incidence was higher in severe VM
      (6.8%) than mild (4.2%). Higher chromosomal abnormality rates were detected when
      VM was isolated (8.6%), rather than associated with any anomaly (3.8%). These
      results suggest that karyotype analysis should be offered to all patients with
      any degree of VM, regardless of its association with structural anomalies.

PMID- 24678818
TI  - Evidence-based triplet delivery: avoiding rocks and hard places.

PMID- 24678819
TI  - Involvement in rehabilitative care and wellbeing for partners of people with an
      amputation.
AB  - The present research aimed to determine if partners' involvement in the
      rehabilitative care of people who have undergone an amputation predicted their
      wellbeing using a quantitative, cross-sectional design. Partners of people with
      an amputation were contacted through amputation-related advocacy groups and asked
      to complete an online questionnaire. Full data were collected from 66
      participants who completed demographic information and measures of perceived
      social support, involvement in partner's rehabilitative care, depression and
      posttraumatic growth. Predictors into the two regression models were chosen based
      on their zero-order correlations with the outcome variables. Only time since
      amputation and degree of prosthesis use were correlated with posttraumatic
      growth. Time since amputation, time in relationship and partner's involvement in
      rehabilitative care were negatively correlated with depression. Both models
      (posttraumatic growth and depression) were significant. Involvement in partner's
      care was an independent significant predictor for depression. More involvement in
      partners' rehabilitative care was a significant predictor of less depression for
      partners of people with an amputation. The present research provides tentative
      evidence in support of the planned inclusion of partners by amputation
      rehabilitation services. Future research is needed to determine how robust this
      finding is.

PMID- 24678821
TI  - Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate-mediated Lossen
      rearrangement: single-pot racemization-free synthesis of hydroxamic acids and
      ureas from carboxylic acids.
AB  - Ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY) mediated Lossen
      rearrangement and its application for the synthesis of ureas is demonstrated.
      Required hydroxamic acids for the Lossen rearrangements were synthesized from
      carboxylic acids using the same reagent. Finally, reaction of an amine with the
      produced isocyanate resulted in urea. Good yields without racemization were
      achieved under milder and simpler reaction conditions. Reactions are compatible
      with common N-protecting groups, such as Boc, Fmoc, Cbz, and benzyl, as well as
      various OH protecting groups, such as (t)Bu and Bzl. Conversion from carboxylic
      acid to urea is achieved in one pot. Most importantly, byproducts Oxyma [ethyl 2
      cyano-2-(hydroxyimino)acetate] and 4-nitrobenzenesulfonic acid can be recovered
      easily and can be recycled to prepare the reagent. Thus, the method is
      environmentally friendly and cost-effective. 

PMID- 24678822
TI  - The kinetics of inhibitor production resulting from hydrothermal deconstruction
      of wheat straw studied using a pressurised microwave reactor.
AB  - BACKGROUND: The use of a microwave synthesis reactor has allowed kinetic data for
      the hydrothermal reactions of straw biomass to be established from short times,
      avoiding corrections required for slow heating in conventional reactors, or two
      step heating. Access to realistic kinetic data is important for predictions of
      optimal reaction conditions for the pretreatment of biomass for bioethanol
      processes, which is required to minimise production of inhibitory compounds and
      to maximise sugar and ethanol yields. RESULTS: The gravimetric loss through
      solubilisation of straw provided a global measure of the extent of hydrothermal
      deconstruction. The kinetic profiles of furan and lignin-derived inhibitors were
      determined in the hydrothermal hydrolysates by UV analysis, with concentrations
      of formic and acetic acid determined by HPLC. Kinetic analyses were either
      carried out by direct fitting to simple first order equations or by numerical
      integration of sequential reactions. CONCLUSIONS: A classical Arrhenius
      activation energy of 148 kJmol-1 has been determined for primary solubilisation,
      which is higher than the activation energy associated with historical measures of
      reaction severity. The gravimetric loss is primarily due to depolymerisation of
      the hemicellulose component of straw, but a minor proportion of lignin is
      solubilised at the same rate and hence may be associated with the more
      hydrophilic lignin-hemicellulose interface. Acetic acid is liberated primarily
      from hydrolysis of pendant acetate groups on hemicellulose, although this occurs
      at a rate that is too slow to provide catalytic enhancement to the primary
      solubilisation reactions. However, the increase in protons may enhance secondary
      reactions leading to the production of furans and formic acid. The work has
      suggested that formic acid may be formed under these hydrothermal conditions via
      direct reaction of sugar end groups rather than furan breakdown. However, furan
      degradation is found to be significant, which may limit ultimate quantities
      generated in hydrolysate liquors.

PMID- 24678820
TI  - Interleukin-17 impedes Schwann cell-mediated myelination.
AB  - BACKGROUND: Pro-inflammatory cytokines are known to have deleterious effects on
      Schwann cells (SCs). Interleukin 17 (IL-17) is a potent pro-inflammatory cytokine
      that exhibits relevant effects during inflammation in the peripheral nervous
      system (PNS), and IL-17-secreting cells have been reported within the endoneurium
      in proximity to the SCs. METHODS: Here, we analyzed the effects of IL-17 on
      myelination and the immunological properties of SCs. Dorsal root ganglia (DRG) co
      cultures containing neurons and SCs from BL6 mice were used to define the impact
      of IL-17 on myelination and on SC differentiation; primary SCs were analyzed for
      RNA and protein expression to define the putative immunological alignment of the
      SCs. RESULTS: SCs were found to functionally express the IL-17 receptors A and B.
      In DRG cultures, stimulation with IL-17 resulted in reduced myelin synthesis,
      while pro-myelin gene expression was suppressed at the mRNA level. Neuronal
      outgrowth and SC viability, as well as structural myelin formation, remained
      unaffected. Co-cultures exhibited SC-relevant pro-inflammatory markers, such as
      matrix metalloproteinase 9 and SCs significantly increased the expression of the
      major histocompatibility complex (MHC) I and exhibited a slight, nonsignificant
      increase in expression of MHCII, and a transporter associated with antigen
      presentation (TAP) II molecules relevant for antigen processing and presentation.
      CONCLUSIONS: IL-17 may act as a myelin-suppressive mediator in the peripheral
      nerve, directly propagating SC-mediated demyelination, paralleled by an
      inflammatory alignment of the SCs. Further analyses are warranted to elucidate
      the role of IL-17 during inflammation in the PNS in vivo, which could be useful
      in the development of target therapies.

PMID- 24678823
TI  - Intraoperative radiotherapy for locally advanced or locally recurrent rectal
      cancer: Does it work at all?
AB  - BACKGROUND: Intraoperative radiotherapy (IORT) has been given for primary and
      locally recurrent rectal cancer for 30 years. Still, its effect is not clear.
      MATERIAL AND METHODS: PubMed and EMBASE search for papers after 1989 on surgical
      treatment and external beam radiotherapy (EBRT) for primary advanced and locally
      recurrent rectal cancer, with and without IORT. From each center the most recent
      paper was generally selected. Survival and local recurrence at five years was
      tabulated for the total groups and separate R-stages. Also, the technique for
      IORT, use of EBRT and chemotherapy as well as surgical approach was registered.
      RESULTS: In primary cancer 18 papers from 14 centers were tabulated, including
      one randomized and five internally comparing studies, as well as seven studies
      without IORT. In locally recurrent cancer 18 papers from 13 centers were
      tabulated, including four internally comparing studies and also five without
      IORT. Overall survival (OS) and local recurrence rate (LRR) were higher for
      primary cancer compared to recurrent cancer. Patients with R0 resections had
      better outcome than patients with R1 or R2 resections. For primary cancer OS and
      LR rate of the total groups and R0 stages was not influenced by IORT. An effect
      on R1/R2 stages cannot be excluded. The only randomized study (primary cancer)
      did not show any effect of IORT. CONCLUSION: IORT does not convincingly improve
      OS and LR rate for primary and locally recurrent rectal cancer. If there is an
      effect of IORT, it is small and cannot be shown outside randomized studies
      analyzing the separate R stages.

PMID- 24678824
TI  - A pilot study of 2 brief forms of dialectical behavior therapy skills training
      for emotion dysregulation in college students.
AB  - OBJECTIVE: To examine the feasibility and initial efficacy of 2 abbreviated
      dialectical behavior therapy (DBT) skills training groups: emotion regulation
      skills only and emotion regulation with mindfulness skills. PARTICIPANTS:
      Participants were 24 undergraduates (aged 18-29) with significant emotion
      dysregulation who participated between February and May of 2010, 2011, and 2012.
      METHODS: Participants participated in 2-hour weekly group sessions for 8 weeks
      and completed outcome measures at baseline, midtreatment, posttreatment, and 4
      week follow-up. RESULTS: Participants in both conditions made significant gains,
      with large effect sizes, across measures of emotion regulation, affect, skills
      use, and functioning. There were no differences between the 2 groups, suggesting
      no additive benefit of mindfulness skills. CONCLUSIONS: This pilot study provides
      support for the acceptability and efficacy of abbreviated DBT skills training in
      colleges, given significant improvements, positive feedback, and low attrition.
      Impediments to feasibility included recruitment difficulties, particularly due to
      scheduling constraints.

PMID- 24678825
TI  - Component analysis of verbal fluency performance in younger participants with
      moderate-to-severe traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To investigate phonemic and semantic verbal fluency
      performance in a group of young adult participants with and without traumatic
      brain injury. RESEARCH DESIGN: Group comparison. METHODS AND PROCEDURES: Twenty
      five participants with moderate-to-severe TBI and 25 participants with no brain
      damage (NBD) were given phonemic and semantic verbal fluency tasks. Responses
      were analysed quantitatively and qualitatively. MAIN OUTCOMES AND RESULTS: Young
      participants with moderate-to-severe TBI generated significantly fewer total
      correct words and sub-categories for both fluency conditions when compared to
      controls. The total number of correct words generated on the phonemic condition
      and for the semantic category of animals was positively correlated with the
      number of category switches produced during the task. CONCLUSIONS: While young
      participants with moderate-to-severe TBI produced fewer total correct words on
      both verbal fluency conditions in comparison to controls, these differences were
      greater on the phonemic condition. Participants with moderate-to-severe TBI
      switched less frequently on both fluency tasks and produced smaller cluster sizes
      only on the phonemic task in comparison to controls. These results are in
      contrast with previous investigations that have observed greater age-related
      declines on semantic tasks when compared to phonemic tasks.

PMID- 24678827
TI  - Electron-beam generated porous dextran gels: experimental and quantum chemical
      studies.
AB  - PURPOSE: The aim of this work was to investigate the reaction mechanism of
      electron-beam generated macroporous dextran cryogels by quantum chemical
      calculation and electron paramagnetic resonance measurements. METHODS: Electron
      beam radiation was used to initiate the cross-linking reaction of methacrylated
      dextran in semifrozen aqueous solutions. The pore morphology of the resulting
      cryogels was visualized by scanning electron microscopy. Quantum chemical
      calculations and electron paramagnetic resonance studies provided information on
      the most probable reaction pathway and the chain growth radicals. RESULTS: The
      most probable reaction pathway was a ring opening reaction and the addition of a
      C-atom to the double-bond of the methacrylated dextran molecule. CONCLUSIONS:
      First detailed quantum chemical calculation on the reaction mechanism of electron
      beam initiated cross-linking reaction of methacrylated dextran are presented.

PMID- 24678826
TI  - Transgenerational epigenetics in the germline cycle of Caenorhabditis elegans.
AB  - Epigenetic mechanisms create variably stable changes in gene expression through
      the establishment of heritable states of chromatin architecture. While many
      epigenetic phenomena are, by definition, heritably passed through cell division
      during animal and plant development, evidence suggests that 'epigenetic states'
      may also be inherited across multiple generations. Work in the nematode
      Caenorhabditis elegans has uncovered a number of mechanisms that participate in
      regulating the transgenerational passage of epigenetic states. These mechanisms
      include some that establish and maintain heritable epigenetic information in the
      form of histone modifications, as well as those that filter the epigenetic
      information that is stably transmitted. The information appears to influence and
      help guide or regulate gene activity and repression in subsequent generations.
      Genome surveillance mechanisms guided by small RNAs appear to be involved in
      identifying and directing heritable repression of genomic elements, and thus may
      participate in filtering information that is inappropriate for stable
      transmission. This review will attempt to summarize recent findings that
      illustrate this simple nematode to be a truly elegant resource for defining
      emerging biological paradigms.As the cell lineage that links generations, the
      germline is the carrier of both genetic and epigenetic information. Like genetic
      information, information in the epigenome can heritably affect gene regulation
      and phenotype; yet unlike genetic information, the epigenome of the germ lineage
      is highly modified within each generation. Despite such alterations, some
      epigenetic information is highly stable across generations, leading to
      transgenerationally stable phenotypes that are unlinked to genetic changes.
      Studies in the nematode C. elegans have uncovered mechanisms that contribute to
      transgenerational repression as well as to the expression of genes that rely on
      histone modifying machinery and/or non-coding RNA-based mechanisms. These studies
      indicate that epigenetic mechanisms operating within the germ cell cycle of this
      organism filter and maintain an epigenetic memory that is required for germ cell
      function and can also influence gene expression in somatic lineages. 

PMID- 24678828
TI  - Computational evidence for the detoxifying mechanism of epsilon class glutathione
      transferase toward the insecticide DDT.
AB  - A combined quantum mechanics/molecular mechanics (QM/MM) computation of the
      detoxifying mechanism of an epsilon class glutathione transferases (GSTs) toward
      organochlorine insecticide DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane,
      has been carried out. The exponential average barrier of the proton transfer
      mechanism is 15.2 kcal/mol, which is 27.6 kcal/mol lower than that of the GS-DDT
      conjugant mechanism. It suggests that the detoxifying reaction proceeds via a
      proton transfer mechanism where GSH acts as a cofactor rather than a conjugate.
      The study reveals that the protein environment has a strong effect on the
      reaction barrier. The experimentally proposed residues Arg112, Glu116 and Phe120
      were found to have a strong influence on the detoxifying reaction. The influence
      of residues Pro13, Cys15, His53, Ile55, Glu67, Ser68, Phe115, and Leu119 was
      detected as well. It is worth noticing that Ile55 facilitates the detoxifying
      reaction most. On the basis of the structure of DDT, structure 2,
      (BrC6H4)2CHCCl3, is the best candidate among all the tested structures in
      resisting the detoxification of enzyme agGSTe2. 

PMID- 24678829
TI  - Carbon-coated Na3V2(PO4)3 embedded in porous carbon matrix: an ultrafast Na
      storage cathode with the potential of outperforming Li cathodes.
AB  - Sodium ion batteries are one of the realistic promising alternatives to the
      lithium analogues. However, neither theoretical energy/power density nor the
      practical values reach the values of Li cathodes. Poorer performance is expected
      owing to larger size, larger mass, and lower cell voltage. Nonetheless, sodium
      ion batteries are considered to be practically relevant in view of the abundance
      of the element Na. The arguments in favor of Li and to the disadvantage of Na
      would be completely obsolete if the specific performance data of the latter would
      match the first. Here we present a cathode consisting of carbon-coated nanosized
      Na3V2(PO4)3 embedded in a porous carbon matrix, which not only matches but even
      outshines lithium cathodes under high rate conditions. It can be (dis)charged in
      6 s with a current density as high as 22 A/g (200 C), still delivering a specific
      capacity of 44 mAh/g, while up to 20 C, the polarization is completely
      negligible. 

PMID- 24678830
TI  - Role of (1,3)(1,4)-beta-glucan in cell walls: interaction with cellulose.
AB  - (1,3)(1,4)-beta-D-Glucan (mixed-linkage glucan or MLG), a characteristic
      hemicellulose in primary cell walls of grasses, was investigated to determine
      both its role in cell walls and its interaction with cellulose and other cell
      wall polysaccharides in vitro. Binding isotherms showed that MLG adsorption onto
      microcrystalline cellulose is slow, irreversible, and temperature-dependent.
      Measurements using quartz crystal microbalance with dissipation monitoring showed
      that MLG adsorbed irreversibly onto amorphous regenerated cellulose, forming a
      thick hydrogel. Oligosaccharide profiling using endo-(1,3)(1,4)-beta-glucanase
      indicated that there was no difference in the frequency and distribution of (1,3)
      and (1,4) links in bound and unbound MLG. The binding of MLG to cellulose was
      reduced if the cellulose samples were first treated with certain cell wall
      polysaccharides, such as xyloglucan and glucuronoarabinoxylan. The tethering
      function of MLG in cell walls was tested by applying endo-(1,3)(1,4)-beta
      glucanase to wall samples in a constant force extensometer. Cell wall extension
      was not induced, which indicates that enzyme-accessible MLG does not tether
      cellulose fibrils into a load-bearing network.

PMID- 24678831
TI  - Plant growth promotion by spermidine-producing Bacillus subtilis OKB105.
AB  - The interaction between plants and plant-growth-promoting rhizobacteria (PGPR) is
      a complex, reciprocal process. On the one hand, plant compounds such as
      carbohydrates and amino acids serve as energy sources for PGPR. On the other
      hand, PGPR promote plant growth by synthesizing plant hormones and increasing
      mineral availability in the soil. Here, we evaluated the growth-promoting
      activity of Bacillus subtilis OKB105 and identified genes associated with this
      activity. The genes yecA (encoding a putative amino acid/polyamine permease) and
      speB (encoding agmatinase) are involved in the secretion or synthesis of
      polyamine in B. subtilis OKB105. Disruption of either gene abolished the growth
      promoting activity of the bacterium, which was restored when polyamine synthesis
      was complemented. Moreover, high-performance liquid chromatography analysis of
      culture filtrates of OKB105 and its derivatives demonstrated that spermidine, a
      common polyamine, is the pivotal plant-growth-promoting compound. In addition,
      real-time polymerase chain reaction analysis revealed that treatment with B.
      subtilis OKB105 induced expansin gene (Nt-EXPA1 and Nt-EXPA2) expression and
      inhibited the expression of the ethylene biosynthesis gene ACO1. Furthermore,
      enzyme-linked immunosorbent assay analysis showed that the ethylene content in
      plant root cells decreased in response to spermidine produced by OKB105.
      Therefore, during plant interactions, OKB105 may produce and secrete spermidine,
      which induces expansin production and lowers ethylene levels. 

PMID- 24678832
TI  - Transcriptome sequencing uncovers the Avr5 avirulence gene of the tomato leaf
      mold pathogen Cladosporium fulvum.
AB  - The Cf-5 gene of tomato confers resistance to strains of the fungal pathogen
      Cladosporium fulvum carrying the avirulence gene Avr5. Although Cf-5 has been
      cloned, Avr5 has remained elusive. We report the cloning of Avr5 using a combined
      bioinformatic and transcriptome sequencing approach. RNA-Seq was performed on the
      sequenced race 0 strain (0WU; carrying Avr5), as well as a race 5 strain (IPO
      1979; lacking a functional Avr5 gene) during infection of susceptible tomato.
      Forty-four in planta-induced C. fulvum candidate effector (CfCE) genes of 0WU
      were identified that putatively encode a secreted, small cysteine-rich protein.
      An expressed transcript sequence comparison between strains revealed two
      polymorphic CfCE genes in IPO 1979. One of these conferred avirulence to IPO 1979
      on Cf-5 tomato following complementation with the corresponding 0WU allele,
      confirming identification of Avr5. Complementation also led to increased fungal
      biomass during infection of susceptible tomato, signifying a role for Avr5 in
      virulence. Seven of eight race 5 strains investigated escape Cf-5-mediated
      resistance through deletion of the Avr5 gene. Avr5 is heavily flanked by
      repetitive elements, suggesting that repeat instability, in combination with Cf-5
      mediated selection pressure, has led to the emergence of race 5 strains deleted
      for the Avr5 gene. 

PMID- 24678833
TI  - The de novo biosynthesis of vitamin B6 is required for disease resistance against
      Botrytis cinerea in tomato.
AB  - Vitamin B6 (VB6), an essential cofactor for numerous metabolic enzymes, has
      recently been shown to act as a potent antioxidant and play important roles in
      developmental processes and stress responses. However, little is known about the
      possible function of VB6 in plant disease resistance response against pathogen
      infection. In the present study, we explored the possible involvement of VB6 in
      defense response against Botrytis cinerea through functional analysis of tomato
      VB6 biosynthetic genes. Three de novo VB6 biosynthetic genes (SlPDX1.2, SlPDX1.3,
      and SlPDX2) and one salvage pathway gene (SlSOS4) were identified and the
      SlPDX1.2, SlPDX1.3, and SlPDX2 genes were shown to encode functional enzymes
      involved in de novo biosynthesis of VB6, as revealed by complementation of the
      VB6 prototrophy in yeast snz1 and sno1 mutants. Expression of SlPDX1.2, SlPDX1.3,
      and SlSOS4 genes was induced by infection with B. cinerea. Virus-induced gene
      silencing-mediated knockdown of SlPDX1.2 or SlPDX1.3 but not SlPDX2 and SlSOS4
      led to increased severity of disease caused by B. cinerea, indicating that the
      VB6 de novo biosynthetic pathway but not the salvage pathway is involved in
      tomato defense response against B. cinerea. Furthermore, the SlPDX1.2- and
      SlPDX1.3-silenced tomato plants exhibited reduced levels of VB6 contents and
      reactive oxygen species scavenging capability, increased levels of superoxide
      anion and H2O2 generation, and increased activity of superoxide dismutase after
      infection by B. cinerea. Our results suggest that VB6 and its de novo
      biosynthetic pathway play important roles in regulation of defense response
      against B. cinerea through modulating cellular antioxidant capacity. 

PMID- 24678834
TI  - Thaxtomin A production and virulence are controlled by several bld gene global
      regulators in Streptomyces scabies.
AB  - Streptomyces scabies is the main causative agent of common scab disease, which
      leads to significant annual losses to potato growers worldwide. The main
      virulence factor produced by S. scabies is a phytotoxic secondary metabolite
      called thaxtomin A, which functions as a cellulose synthesis inhibitor. Thaxtomin
      A production is controlled by the cluster-situated regulator TxtR, which
      activates expression of the thaxtomin biosynthetic genes in response to cello
      oligosaccharides. Here, we demonstrate that at least five additional regulatory
      genes are required for wild-type levels of thaxtomin A production and plant
      pathogenicity in S. scabies. These regulatory genes belong to the bld gene family
      of global regulators that control secondary metabolism or morphological
      differentiation in Streptomyces spp. Quantitative reverse-transcriptase
      polymerase chain reaction showed that expression of the thaxtomin biosynthetic
      genes was significantly downregulated in all five bld mutants and, in four of
      these mutants, this downregulation was attributed to the reduction in expression
      of txtR. Furthermore, all of the mutants displayed reduced expression of other
      known or predicted virulence genes, suggesting that the bld genes may function as
      global regulators of virulence gene expression in S. scabies. 

PMID- 24678835
TI  - Single amino acid mutations in the potato immune receptor R3a expand response to
      Phytophthora effectors.
AB  - Both plants and animals rely on nucleotide-binding domain and leucine-rich repeat
      containing (NB-LRR or NLR) proteins to respond to invading pathogens and activate
      immune responses. How plant NB-LRR proteins respond to pathogens is poorly
      understood. We undertook a gain-of-function random mutagenesis screen of the
      potato NB-LRR immune receptor R3a to study how this protein responds to the
      effector protein AVR3a from the oomycete pathogen Phytophthora infestans. R3a
      response can be extended to the stealthy AVR3aEM isoform of the effector while
      retaining recognition of AVR3aKI. Each one of eight single amino acid mutations
      is sufficient to expand the R3a response to AVR3aEM and other AVR3a variants.
      These mutations occur across the R3a protein, from the N terminus to different
      regions of the LRR domain. Further characterization of these R3a mutants revealed
      that at least one of them was sensitized, exhibiting a stronger response than the
      wild-type R3a protein to AVR3aKI. Remarkably, the N336Y mutation, near the R3a
      nucleotide-binding pocket, conferred response to the effector protein PcAVR3a4
      from the vegetable pathogen P. capsici. This work contributes to understanding
      how NB-LRR receptor specificity can be modulated. Together with knowledge of
      pathogen effector diversity, this strategy can be exploited to develop synthetic
      immune receptors.

PMID- 24678836
TI  - In situ building of a nanoprobe based on fluorescent carbon dots for
      methylmercury detection.
AB  - A new fluorescent assay based on in situ ultrasound-assisted synthesis of carbon
      dots (CDs) as optical nanoprobes for the detection of methylmercury has been
      developed. Application of high-intensity sonication allows simultaneous
      performance of the synthesis of fluorescent CDs within the analytical time scale
      and the selective recognition of the target analyte. Microvolume
      fluorospectrometry is applied for measurement of the fluorescence quenching
      caused by methylmercury. The assay uses low amounts of organic precursors
      (fructose, poly(ethylene glycol), and ethanol) and can be accomplished within 1
      min. A detection limit of 5.9 nM methylmercury and a repeatability expressed as a
      relative standard deviation of 2.2% (N = 7) were obtained. CDs displayed a narrow
      size distribution with an average size of 2.5 nm as determined by electron
      transmission microscopy. To study the quenching mechanism, fluorescence, atomic
      absorption spectrometry, and Fourier transform infrared spectrometry were
      applied. Hydrophobicity of methylmercury and its ability to facilitate a
      nonradiative electron/hole recombination are suggested as the basis of the
      recognition event. A simple and green assay is achieved for quick detection of
      methylmercury without the use of tedious sample preparation procedures or complex
      and expensive instrumentation. 

PMID- 24678837
TI  - Predicting battlefield vigilance: a multivariate approach to assessment of
      attentional resources.
AB  - Technological innovation increasingly requires operators in various applied
      settings to maintain vigilance for extended periods. However, standard
      psychometric tests typically predict less than 10% of performance variance. The
      present study (N = 462) aimed to apply the resource theory of sustained attention
      to construct a multivariate test battery for predicting battlefield vigilance.
      The battery included cognitive ability tests, a high-workload short vigilance
      task and subjective measures of stress response. Four versions of a 60- min
      simulated military battlefield monitoring task were constructed to represent
      different operational requirements. The test battery predicted 24-44% of
      criterion variance, depending on task version, suggesting that it may identify
      vigilant operators in military and other applied contexts. A multiple-groups path
      analysis showed that relationships between ability and vigilance were moderated
      by working memory demands. Findings are consistent with a diffuse theoretical
      concept of 'resources' in which performance energisation depends on multiple,
      loosely coupled processes. 

PMID- 24678838
TI  - Comparative study of cardio-ankle vascular index between Chinese and Japanese
      healthy subjects.
AB  - OBJECTIVES: Arterial stiffness is an independent predictor for vascular diseases.
      Cardio-ankle vascular index (CAVI) is a new index of arterial stiffness. However,
      there was little research about the CAVI value between different countries. The
      aim of the present study was to compare CAVI between Chinese and Japanese
      subjects and to assess related factors. METHODS: 2519 healthy persons [1245
      Chinese (M/F, 524/721) and 1274 Japanese (M/F, 534/740)] from the Department of
      Physical Examination were enrolled into our study. CAVI was recorded using a
      VaseraVS-1000 vascular screening system. RESULTS: CAVI was increasing with aging
      in all subjects. CAVI was significantly lower in Chinese compared with Japanese
      both in male and female. There was difference in lipid metabolism between these
      two groups. Multivariate analysis showed that age, systolic blood pressure (SBP),
      fasting plasma glucose (FPG), plasma creatinine (Cr) were significant independent
      associating factors of CAVI in Chinese persons (beta = 0.548, p < 0.001; beta =
      0.129, p = 0.001; beta = 0.105, p = 0.006; and beta = 0.100, p = 0.012,
      respectively), whereas age, SBP, high-density lipoprotein cholesterol (HDL-C),
      Cr, body mass index (BMI), FPG were significant independent associating factors
      of CAVI in Japanese subjects (beta = 0.669, p < 0.001; beta = 0.198, p < 0.001;
      beta = -0.079, p < 0.001; beta = 0.090, p < 0.001; beta = -0.124, p < 0.001; beta
      = 0.055, p=0.009; respectively). CONCLUSIONS: CAVI was increasing with aging in
      both Chinese and Japanese subjects. CAVI was significantly lower in Chinese than
      in Japanese subjects. Age, SBP, FPG and creatinine were independently associated
      with CAVI in both Chinese and Japanese subjects.

PMID- 24678839
TI  - Developing and implementing a service charter for an integrated regional stroke
      service: an exploratory case study.
AB  - BACKGROUND: Based on practices in commercial organizations and public services,
      healthcare organizations are using service charters to inform patients about the
      quality of service they can expect and to increase patient-centeredness. In the
      Netherlands, an integrated regional stroke service involving five organizations
      has developed and implemented a single service charter. The purpose of this study
      is to determine the organizational enablers for the effective development and
      implementation of this service charter. METHODS: We have conducted an exploratory
      qualitative study using Grounded Theory to determine the organizational enablers
      of charter development and implementation. Individual semi-structured interviews
      were held with all members of the steering committee and the taskforce
      responsible for the service charter. In these twelve interviews, participants
      were retrospectively asked for their opinions of the enablers. Interview
      transcripts have been analysed using Glaser's approach of substantive coding
      consisting of open and selective coding in order to develop a framework of these
      enablers. A tabula rasa approach was used without any preconceived frameworks
      used in the coding process. RESULTS: We have determined seven categories of
      enablers formed of a total of 27 properties. The categories address a broad
      spectrum of enablers dealing with the basic foundations for cooperation, the way
      to manage the project's organization and the way to implement the service
      charter. In addition to the enablers within each individual organization,
      enablers that reflect the whole chain seem to be important for the effective
      development and implementation of this service charter. Strategic alignment of
      goals within the chain, trust between organizations, willingness to cooperate and
      the extent of process integration are all important properties. CONCLUSIONS: This
      first exploratory study into the enablers of the effective development and
      implementation was based on a single case study in the Netherlands. This is the
      only integrated care chain using a single service charter that we could find.
      Nevertheless, the results of our explorative study provide an initial framework
      for the development and implementation of service charters in integrated care
      settings. This research contributes to the literature on service charters, on
      patient-centeredness in integrated care and on the implementation of innovations.

PMID- 24678840
TI  - Synthesis of 2'-hydroxy-4'-isoprenyloxychalcone derivatives with potential
      antidepressant-like activity.
AB  - A series of 2'-hydroxy-4'-isoprenyloxychalcone derivatives was synthesized and
      evaluated for its antidepressant- like activity using the FST and TST. All
      compounds exhibited the potential antidepressant-like activity in the FST and the
      TST through intraperitoneal injection. Among them, compounds 4i, 4l and 4n
      exhibited more potent antidepressant- like activity at a dose of 10 mg/kg. And,
      compounds 4i, 4l and 4n were also adequately absorbed in mice after oral
      administration at a dose of 30 mg/kg. In the 5-HT induced head-twitch test and
      yohimbine induced mortality test, compound 4i could increase the head-twitch and
      rise mortality in mice. The results suggested that the antidepressant effects of
      compound 4i may be related to via the serotonergic and noradrenergic system.

PMID- 24678841
TI  - Selection for complex traits leaves little or no classic signatures of selection.
AB  - BACKGROUND: Selection signatures aim to identify genomic regions underlying
      recent adaptations in populations. However, the effects of selection in the
      genome are difficult to distinguish from random processes, such as genetic drift.
      Often associations between selection signatures and selected variants for complex
      traits is assumed even though this is rarely (if ever) tested. In this paper, we
      use 8 breeds of domestic cattle under strong artificial selection to investigate
      if selection signatures are co-located in genomic regions which are likely to be
      under selection. RESULTS: Our approaches to identify selection signatures
      (haplotype heterozygosity, integrated haplotype score and FST) identified strong
      and recent selection near many loci with mutations affecting simple traits under
      strong selection, such as coat colour. However, there was little evidence for a
      genome-wide association between strong selection signatures and regions affecting
      complex traits under selection, such as milk yield in dairy cattle. Even
      identifying selection signatures near some major loci was hindered by factors
      including allelic heterogeneity, selection for ancestral alleles and interactions
      with nearby selected loci. CONCLUSIONS: Selection signatures detect loci with
      large effects under strong selection. However, the methodology is often assumed
      to also detect loci affecting complex traits where the selection pressure at an
      individual locus is weak. We present empirical evidence to suggests little
      discernible 'selection signature' for complex traits in the genome of dairy
      cattle despite very strong and recent artificial selection.

PMID- 24678843
TI  - Could nitrile derivatives of turnip (Brassica rapa) glucosinolates be hepato- or
      cholangiotoxic in cattle?
AB  - Turnip (Brassica rapa ssp. rapa) and rape (Brassica napus ssp. biennis) and other
      brassica forage crops are regarded as "safe" feed for cattle during late summer
      and fall in the North Island of New Zealand when high Pithomyces chartarum spore
      counts in pastures frequently lead to sporidesmin toxicity (facial eczema).
      Sporadic acute severe cases of turnip photosensitization in dairy cows
      characteristically exhibit high gamma-glutamyl transferase and glutamate
      dehydrogenase serum enzyme activities that mimic those seen in facial eczema. The
      two diseases can, however, be distinguished by histopathology of the liver, where
      lesions, in particular those affecting small bile ducts, differ. To date, the
      hepato-/cholangiotoxic phytochemical causing liver damage in turnip
      photosensitization in cattle is unknown. Of the hydrolysis products of the
      various glucosinolate secondary compounds found in high concentrations in turnip
      and rape, work has shown that nitriles and epithionitriles can be hepatotoxic
      (and nephro- or pancreatotoxic) in rats. These derivatives include beta-hydroxy
      thiiranepropanenitrile and 3-hydroxy-4-pentenenitrile from progoitrin;
      thiiranepropanenitrile and 4-pentenenitrile from gluconapin;
      thiiranebutanenitrile and 5-hexenenitrile from glucobrassicanapin; phenyl-3
      propanenitrile from gluconasturtiin; and indole-3-acetonitrile from
      glucobrassicin. This perspective explores the possibility of the preferential
      formation of such derivatives, especially the epithionitriles, in acidic
      conditions in the bovine rumen, followed by absorption, hepatotoxicity, and
      secondary photosensitization. 

PMID- 24678844
TI  - Mutagenesis analysis of T380R mutation in the envelope protein of yellow fever
      virus.
AB  - BACKGROUND: The RGD motif in the mosquito-borne flaviviruses envelope protein
      domain III (EDIII) FG loop was shown to bind negatively charged cellular
      molecules and mediate virus entry in mammals. However, its importance in virus
      entry in the mosquito has not yet been defined. The sequences of RGD motifs are
      conserved in JEV-serocomplex members primarily transmitted by Culex mosquitoes
      but absent from members of the DENV serocomplex, which utilize Aedes mosquitoes
      as vectors. Interestingly, the RGD sequence is present in the attenuated 17D
      strain of yellow fever virus as a result of the T380R mutation in the EDIII of
      Asibi strain following extensive in vitro passage in mice and chicken embryos and
      was found to contribute to the more rapid clearance in mice challenged with 17D.
      However, viral infectivity and dissemination in mosquitoes had not been evaluated
      for this mutant. FINDINGS: The study utilized the reverse genetics system of YFV
      and Ae. aegypti RexD WE mosquitoes to assess the impact of a T380R mutation in
      YFV Asibi and 17D/Asibi M-E chimera. The T380R mutation led to higher infection
      rates but similar dissemination rates when introduced into the YFV Asibi strain
      and 17D/Asibi M-E chimera. CONCLUSIONS: While the increase of the positive charge
      in EDIII may reduce the virulence of YFV in mice, this mutation favored the
      establishment of the viral infection in Ae. aegypti. However, such gain in viral
      infectivity did not increase dissemination in infected mosquitoes.

PMID- 24678846
TI  - Variation in voxel value distribution and effect of time between exposures in six
      CBCT units.
AB  - The aim of this study is to assess the variation in voxel value distribution in
      volumetric data sets obtained by six cone beam CT (CBCT) units, and the effect of
      time between exposures. Six CBCT units [Cranex((r)) 3D (CRAN; Soredex Oy,
      Tuusula, Finland), Scanora((r)) 3D (SCAN; Soredex Oy), NewTomTM 5G (NEWT; QR Srl,
      Verona, Italy), Promax((r)) Dimax 3 (Planmeca Oy, Helsinki, Finland), i-CAT
      (Imaging Sciences International, Hatfield, PA) and 3D Accuitomo FPD80 (Morita,
      Kyoto, Japan)] were tested. Two volumetric data sets of a dry human skull
      embedded in acrylic were acquired by each CBCT unit in two sessions on separate
      days. Each session consisted of 20 exposures: 10 acquired with 30 min between
      exposures and 10 acquired immediately one after the other. CBCT data were
      exported as digital imaging and communications in medicine (DICOM) files and
      converted to text files. The text files were re-organized to contain x-, y- and z
      position and grey shade for each voxel. The files were merged to contain 1 record
      per voxel position, including the voxel values from the 20 exposures in a
      session. For each voxel, subtractions were performed between Data Set 1 and the
      remaining 19 data sets (1 - 2, 1 - 3, etc) in a session. Means, medians, ranges
      and standard deviations for grey shade variation in the subtraction data sets
      were calculated for each unit and session. For all CBCT units, variation in voxel
      values was observed throughout the 20 exposures. A "fingerprint" for the grey
      shade variation was observed for CRAN, SCAN and NEWT. For the other units, the
      variation was (apparently) randomly distributed. Large discrepancies in voxel
      value distribution are seen in CBCT images. This variation should be considered
      in studies that assess minute changes in CBCT images. 

PMID- 24678845
TI  - Interrogating causal pathways linking genetic variants, small molecule
      metabolites, and circulating lipids.
AB  - BACKGROUND: Emerging technologies based on mass spectrometry or nuclear magnetic
      resonance enable the monitoring of hundreds of small metabolites from tissues or
      body fluids. Profiling of metabolites can help elucidate causal pathways linking
      established genetic variants to known disease risk factors such as blood lipid
      traits. METHODS: We applied statistical methodology to dissect causal
      relationships between single nucleotide polymorphisms, metabolite concentrations,
      and serum lipid traits, focusing on 95 genetic loci reproducibly associated with
      the four main serum lipids (total-, low-density lipoprotein-, and high-density
      lipoprotein- cholesterol and triglycerides). The dataset used included 2,973
      individuals from two independent population-based cohorts with data for 151 small
      molecule metabolites and four main serum lipids. Three statistical approaches,
      namely conditional analysis, Mendelian randomization, and structural equation
      modeling, were compared to investigate causal relationship at sets of a single
      nucleotide polymorphism, a metabolite, and a lipid trait associated with one
      another. RESULTS: A subset of three lipid-associated loci (FADS1, GCKR, and LPA)
      have a statistically significant association with at least one main lipid and one
      metabolite concentration in our data, defining a total of 38 cross-associated
      sets of a single nucleotide polymorphism, a metabolite and a lipid trait.
      Structural equation modeling provided sufficient discrimination to indicate that
      the association of a single nucleotide polymorphism with a lipid trait was
      mediated through a metabolite at 15 of the 38 sets, and involving variants at the
      FADS1 and GCKR loci. CONCLUSIONS: These data provide a framework for evaluating
      the causal role of components of the metabolome (or other intermediate factors)
      in mediating the association between established genetic variants and diseases or
      traits.

PMID- 24678847
TI  - Expression of pro-inflammatory mediators is inhibited by an avocado/soybean
      unsaponifiables and epigallocatechin gallate combination.
AB  - BACKGROUND: Osteoarthritis (OA) is characterized by inflammation, joint
      immobility, and pain. Non-pharmacologic agents modulating pro-inflammatory
      mediator expression offer considerable promise as safe and effective treatments
      for OA. We previously determined the anti-inflammatory effect of an
      avocado/soybean unsaponifiables (ASU) and epigallocatechin gallate (EGCG)
      combination on prostaglandin E2 (PGE2) production and nuclear factor-kappa B (NF
      kappaB) translocation. The aim of this study was to evaluate the effects of ASU +
      EGCG on pro-inflammatory gene expression. FINDINGS: Articular chondrocytes from
      carpal joints of mature horses were pre-incubated for 24 hours with control media
      alone or ASU (8.3 MUg/mL) + EGCG (40 ng/mL), followed by one hour activation with
      interleukin-1 beta (IL-1beta, 10 ng/mL) and tumor necrosis factor-alpha (TNF
      alpha, 1 ng/mL). Total cellular RNA was isolated and real-time PCR performed to
      measure IL-1beta, TNF-alpha, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and
      interleukin-8 (IL-8) gene expression. Intracellular localization of NF-kappaB was
      analyzed by immunohistochemistry and Western blot. Pre-treatment with ASU + EGCG
      significantly (P < 0.001) decreased gene expression of IL-1beta, TNF-alpha, IL-6,
      COX-2, and IL-8 in cytokine-activated chondrocytes. Western blot and
      immunostaining confirmed NF-kappaB translocation inhibition. CONCLUSIONS: We
      demonstrate that ASU + EGCG inhibits cytokine-induced gene expression of IL
      1beta, TNF-alpha, IL-6, COX-2, and IL-8 through modulation of NF-kappaB. Our
      results indicate that the activity of ASU + EGCG affects a wide array of
      inflammatory molecules in addition to decreasing PGE2 synthesis in activated
      chondrocytes. The responsiveness of chondrocytes to this combination supports its
      potential utility for the inhibition of joint inflammation.

PMID- 24678848
TI  - The role of positive alcohol expectancies in underage binge drinking among
      college students.
AB  - OBJECTIVE: This study explored associations between positive alcohol
      expectancies, and demographics, as well as academic status and binge drinking
      among underage college students. PARTICIPANTS: A sample of 1,553 underage college
      students at 3 public universities and 1 college in the Southeast who completed
      the Core Alcohol and Drug Survey in the Spring 2013 semester. METHODS: A series
      of bivariate analyses and logistic regression models were used to examine
      associations between demographic and academic status variables as well as
      positive alcohol expectancies with self-reported binge drinking. Positive alcohol
      expectancies were examined in multivariable models via 2 factors derived from
      principal component analyses. RESULTS: Students who endorsed higher agreement of
      these 2 emergent factors (sociability, sexuality) were more likely to report an
      occurrence of binge drinking in the past 2 weeks. CONCLUSIONS: Study results
      document associations between positive alcohol expectancies and binge drinking
      among underage students; implications for prevention and treatment are discussed.

PMID- 24678849
TI  - Nonracemic synthesis of GK-GKRP disruptor AMG-3969.
AB  - A nonracemic synthesis of the glucokinase-glucokinase regulatory protein
      disruptor AMG-3969 (5) is reported. Key features of the synthetic approach are an
      asymmetric synthesis of the 2-alkynyl piperazine core via a base-promoted
      isomerization and a revised approach to the synthesis of the
      aminopyridinesulfonamide with an improved safety profile.

PMID- 24678850
TI  - Alveolar bone resorption induced by CD4+CD45RB high-density T-cell transfer in
      immunocompromised mice.
AB  - BACKGROUND: The aims of this study are to determine whether the antigen
      inexperienced (naive, CD45RB high-density) T-cell (CD4(+)CD45RB(High) T-cell)
      transfer model is associated with alveolar bone resorption, to elucidate the
      local osteogenic/adipogenic potential of alveolar bone marrow stromal cells
      (ABCs) from T-cell-transferred animals, and to investigate the systemic
      osteogenic potential by transplanting human periodontal ligament stem cells
      (hPDLSCs) into these animals. METHODS: CD4(+)CD45RB(High) and CD4(+)CD45RB(Low)
      (antigen-experienced [memory, CD45RB low-density]) T cells were sorted and
      transferred into severe combined immunodeficiency (SCID) mice to induce
      inflammatory bowel disease-like syndrome (n = 8). hPDLSCs were transplanted into
      T-cell-transferred SCID mice to examine ectopic cementum formation 8 weeks after
      T-cell transfer. The mandibles and tibias of these mice were retrieved for
      microcomputed tomography (micro-CT), histomorphometric analysis, and isolation of
      ABCs 16 weeks after T-cell transfer. The in vitro osteogenic and adipogenic
      potentials of the ABCs were evaluated. RESULTS: Histologic and micro-CT analysis
      revealed that the transfer of CD4(+)CD45RB(High) T-cell subset was sufficient for
      alveolar bone resorption and affected the osteogenic/adipogenic potential of
      ABCs. Furthermore, it was found that CD4(+)CD45RB(High) T-cell-transferred
      animals have decreased systemic osteogenic potential, as evidenced using the in
      vivo ectopic hPDLSC transplantation model. CONCLUSION: CD4(+)CD45RB(High) T-cell
      transfer induced both alveolar bone resorption and reduced systemic osteogenic
      potential, with a concomitant downregulation of the osteogenic potential of ABCs.

PMID- 24678851
TI  - Tumor necrosis factor-alpha and oral inflammation in patients with Crohn disease.
AB  - BACKGROUND: Crohn disease (CD) is a chronic inflammatory bowel disease often
      accompanied by periodontal symptoms. Based on its function in immune response,
      tumor necrosis factor (TNF)-alpha and its genetic variants have been discussed as
      risk indicators in inflammatory processes. Therefore, the aim of the present
      study is to investigate the impact of TNF-alpha polymorphisms on periodontal
      parameters and inflammatory lesions of oral mucosa as a characteristic of CD.
      METHODS: A total of 142 patients with CD were included in the study. Oral soft
      tissue alterations and periodontal parameters were assessed. Genotypes, alleles,
      and haplotypes of TNF-alpha polymorphisms (rs1800629, cDNA-308G > A; and
      rs361525, cDNA-238G > A) were determined by polymerase chain reaction with
      sequence-specific primers (PCR-SSP). RESULTS: Patients with CD who exhibit more
      severe oral soft tissue alterations were significantly more often A allele
      carriers of rs361525 than G allele carriers (14.2% versus 2.2%; P <0.001).
      Furthermore, A allele carriers had a higher mean periodontal probing depth (P
      <0.05), mean clinical attachment level (P <0.05), and sites with bleeding on
      probing (not significant). Similar results were obtained when evaluating A allele
      containing genotypes (AG + AA) and haplotypes (GA). In multivariate analyses
      considering age, sex, smoking, and medication as confounders, the A allele was
      proven to be an independent risk indicator for oral soft tissue alterations in
      patients with CD. No genotype-dependent influence of rs1800629 was observed.
      CONCLUSION: The TNF-alpha A allele of rs361525 represents a significant risk
      indicator for oral soft tissue alterations in patients with CD.

PMID- 24678852
TI  - Next-generation snake venomics: protein-locus resolution through venom proteome
      decomplexation.
AB  - Venom research has been continuously enhanced by technological advances. High
      throughput technologies are changing the classical paradigm of hypothesis-driven
      research to technology-driven approaches. However, the thesis advocated in this
      paper is that full proteome coverage at locus-specific resolution requires
      integrating the best of both worlds into a protocol that includes decomplexation
      of the venom proteome prior to liquid chromatography-tandem mass spectrometry
      matching against a species-specific transcriptome. This approach offers the
      possibility of proof-checking the species-specific contig database using
      proteomics data. Immunoaffinity chromatography constitutes the basis of an
      antivenomics workflow designed to quantify the extent of cross-reactivity of
      antivenoms against homologous and heterologous venom toxins. In the author's
      view, snake venomics and antivenomics form part of a biology-driven conceptual
      framework to unveil the genesis and natural history of venoms, and their within-
      and between-species toxicological and immunological divergences and similarities.
      Understanding evolutionary trends across venoms represents the Rosetta Stone for
      generating broad-ranging polyspecific antivenoms.

PMID- 24678854
TI  - Implementation of the WHO Surgical Safety Checklist in an Ethiopian Referral
      Hospital.
AB  - BACKGROUND: The WHO Surgical Safety Checklist has a growing evidence base to
      support its role in improving perioperative safety, although its impact is likely
      to be directly related to the effectiveness of its implementation. There remains
      a paucity of documented experience from low-resource settings on Checklist
      implementation approaches. We report an implementation strategy in a public
      referral hospital in Addis Ababa, Ethiopia, based on consultation, local
      leadership, formal introduction, and supported supervision with subsequent audit
      and feedback. METHODS: Planning, implementation and assessment took place from
      December 2011 to December 2012. The planning phase, from December 2011 until
      April 2012, involved a multidisciplinary consultative approach using local
      leaders, volunteer clinicians, and staff from non-governmental organisations, to
      draw up a locally agreed and appropriate Checklist. Implementation in April 2012
      involved formal teaching and discussion, simulation sessions and role play, with
      supportive supervision following implementation. Assessment was performed using
      completed Checklist analysis and staff satisfaction questionnaires at one month
      and further Checklist analysis combined with semi-structured interviews in
      December 2012. RESULTS AND DISCUSSION: Checklist compliance rates were 83% for
      general anaesthetics at one month after implementation, with an overall
      compliance rate of 65% at eight months. There was a decrease in Checklist
      compliance over the period of the study to less than 20% by the end of the study
      period. The 'Sign out' section was reported as being the most difficult section
      of the Checklist to complete, and was missed completely in 21% of cases. The most
      commonly missed single item was the team introduction at the start of each case.
      However, we report high staff satisfaction with the Checklist and enthusiasm for
      its continued use. CONCLUSION: We report a detailed implementation strategy for
      introducing the WHO Surgical Safety Checklist to a low-resource setting. We show
      that this approach can lead to high completion rates and high staff satisfaction,
      albeit with a drop in completion rates over time. We argue that maximal benefit
      of the Surgical Safety Checklist is likely to be when it engenders a conversation
      around patient safety within a department, and when there is local ownership of
      this process.

PMID- 24678853
TI  - Breast density and mode of detection in relation to breast cancer specific
      survival: a cohort study.
AB  - BACKGROUND: The aim of this study was to examine breast density in relation to
      breast cancer specific survival and to assess if this potential association was
      modified by mode of detection. An additional aim was to study whether the
      established association between mode of detection and survival is modified by
      breast density. METHODS: The study included 619 cases from a prospective cohort,
      The Malmo Diet and Cancer Study. Breast density estimated qualitatively, was
      analyzed in relation to breast cancer death, in non-symptomatic and symptomatic
      women, using Cox regression calculating hazard ratios (HR) with 95% confidence
      intervals. Adjustments were made in several steps for; diagnostic age, tumour
      size, axillary lymph node involvement, grade, hormone receptor status, body mass
      index (baseline), diagnostic period, use of hormone replacement therapy at
      diagnosis and mode of detection. Detection mode in relation to survival was
      analyzed stratified for breast density. Differences in HR following different
      adjustments were analyzed by Freedmans%. RESULTS: After adjustment for age and
      other prognostic factors, women with dense, as compared to fatty breasts, had an
      increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically
      significant trend over density categories, p = 0.04. In the stratified analysis,
      the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as
      compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic
      women had a higher risk of breast cancer death, regardless of breast density.
      Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period,
      ER and PgR explained 55.5% of the observed differences in mortality between non
      symptomatic and symptomatic cases. Additional adjustment for breast density
      caused only a minor change. CONCLUSIONS: High breast density at diagnosis may be
      associated with decreased breast cancer survival. This association appears to be
      stronger in women with symptomatic cancers but breast density could not explain
      differences in survival according to detection mode.

PMID- 24678855
TI  - Relationship between blood pressure response during step exercise test and
      atherosclerotic markers.
AB  - Abstract The relationship between blood pressure (BP) response to exercise and
      atherosclerotic markers were evaluated in a population based sample of 426
      normotensive subjects. The subjects with greater increase of SBP during exercise
      and delayed recovery of SBP after exercise showed higher hs-CRP and SBP2.
      Multiple regression analysis revealed that the greater BP response and delayed BP
      recovery were independently associated with SBP2 after adjusting for resting SBP,
      age, and gender. These results suggest that early atherosclerosis may contribute
      to greater BP responses to exercise, supporting the concept that exercise BP adds
      incremental information of cardiovascular risks to resting BP. 

PMID- 24678856
TI  - An investigation of the radiation doses to the lower legs and feet of staff
      undertaking interventional procedures.
AB  - OBJECTIVE: Occupational radiation doses from fluoroscopic procedures are some of
      the highest doses of exposure amongst medical staff using radiography. Protective
      equipment and dose monitoring are used to minimize and control the risk from
      these occupational doses. Other studies have considered the effectiveness of this
      protection, but this study further considers whether protection is adequate for
      the lower leg and foot and the extent to which these doses can be reduced.
      METHODS: Scatter air kerma profiles at toe level were measured with an ionization
      chamber. Thermoluminescent dosemeters and lower extremity phantoms were used to
      estimate the dose variation with the height of patient couch. A 7-week period of
      in situ toe dose monitoring of four radiologists was also undertaken. RESULTS:
      The use of protective curtains effectively reduced the exposure to most of the
      lower extremities. Toe doses were found to be high and increased with increase in
      couch height. In situ monitoring indicated annual toe doses of 110 mSv for two of
      the four radiologists monitored. CONCLUSION: Protective curtains should be used,
      but they might have limitations with respect to toe doses. Annual toe doses
      approaching the classification threshold of 150 mSv were measured for two
      radiologists. Caution should be exercised when there is a gap below curtains and,
      when possible, staff should step back from the couch. Lower legs and toes should
      be included in local radiation protection programmes. ADVANCES IN KNOWLEDGE: Toe
      doses in interventional radiology may be higher than expected and may have to be
      included in radiation protection programmes.

PMID- 24678857
TI  - Large-area synthesis of monolayer and few-layer MoSe2 films on SiO2 substrates.
AB  - We present successful synthesis of large area atomically thin MoSe2 films by
      selenization of MoO3 in a vapor transport chemical vapor deposition (CVD) system.
      The homogeneous thin film can reach an area of 1 * 1 cm(2) consisting primarily
      of monolayer and bilayer MoSe2 film. Scanning transmission electron microscopy
      (STEM) images reveal the highly crystalline nature of the thin film and the
      atomic structure of grain boundaries in monolayers. Raman and photoluminescence
      spectroscopy confirm the high quality of as-grown MoSe2 in optics, and electronic
      transport measurements highlight the potential applications of the sample in
      nanoelectronics. 

PMID- 24678858
TI  - Recombinant spider silk genetically functionalized with affinity domains.
AB  - Functionalization of biocompatible materials for presentation of active protein
      domains is an area of growing interest. Herein, we describe a strategy for
      functionalization of recombinant spider silk via gene fusion to affinity domains
      of broad biotechnological use. Four affinity domains of different origin and
      structure; the IgG-binding domains Z and C2, the albumin-binding domain ABD, and
      the biotin-binding domain M4, were all successfully produced as soluble silk
      fusion proteins under nondenaturing purification conditions. Silk films and
      fibers produced from the fusion proteins were demonstrated to be chemically and
      thermally stable. Still, the bioactive domains are concluded to be folded and
      accessible, since their respective targets could be selectively captured from
      complex samples, including rabbit serum and human plasma. Interestingly,
      materials produced from mixtures of two different silk fusion proteins displayed
      combined binding properties, suggesting that tailor-made materials with desired
      stoichiometry and surface distributions of several binding domains can be
      produced. Further, use of the IgG binding ability as a general mean for
      presentation of desired biomolecules could be demonstrated for a human vascular
      endothelial growth factor (hVEGF) model system, via a first capture of anti-VEGF
      IgG to silk containing the Z-domain, followed by incubation with hVEGF. Taken
      together, this study demonstrates the potential of recombinant silk, genetically
      functionalized with affinity domains, for construction of biomaterials capable of
      presentation of almost any desired biomolecule. 

PMID- 24678860
TI  - Microgravimetric thermodynamic modeling for optimization of chemical sensing
      nanomaterials.
AB  - On the basis of microgravimetric sensing data, an analytical modeling method is
      proposed for comprehensive evaluation and optimization of gas sensing or
      adsorbing related functional materials. Resonant microcantilever is loaded with
      the material to be evaluated for a gravimetric sensing experiment. With sensing
      isotherm curves obtained at different temperatures, key thermodynamic and kinetic
      parameters of the material, such as enthalpy DeltaH degrees , Gibbs free energy,
      adsorption rate constant Ka, and coverage theta, etc., can be quantitatively
      extracted for optimal selection and design. On the basis of the gravimetric
      experiment, the modeling method is used on three sorts of trimethylamine sensing
      nanomaterials of mesoporous silica nanoparticles (MSNs). The COOH-functionalized
      material is clearly identified as the best sensing material among the three
      similar ones, thereby validating high accuracy of the proposed model. Broad
      applicability of the modeling method to other sensing materials and/or target
      gases is also experimentally confirmed, where sensing properties of a
      functionalized hyper-branched polymer to organophorous simulant of dimethyl
      methylphosphonate (DMMP) are still evaluated well. In addition to sensing
      materials, the gravimetric experiment-based modeling method can be expanded to
      other functional materials like moisture absorbents or detoxification agents.
      Water adsorbing experiment on KIT-5 mesoporous-silica is modeled, with the low 
      DeltaH degrees  value (i.e., low adsorption heat) result, indicating that the KIT
      5 is a good adsorbent to humidity. Alternatively, the modeled high -DeltaH
      degrees  value (i.e., high reaction heat) shows promising usage of SBA-15
      mesoporous-silica as detoxification material to hazardous organophorous
      chemicals. Therefore, the analytical modeling technology can be used for
      developing and evaluating new adsorbing materials for gas sensing, fixing, and
      detoxification applications. 

PMID- 24678859
TI  - Perfusion reduction at transcatheter intraarterial perfusion MR imaging: a
      promising intraprocedural biomarker to predict transplant-free survival during
      chemoembolization of hepatocellular carcinoma.
AB  - PURPOSE: To investigate the predictive value of transcatheter intraarterial
      perfusion (TRIP) magnetic resonance (MR) imaging-measured tumor perfusion changes
      during transarterial chemoembolization on transplant-free survival (TFS) in
      patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      This HIPAA-compliant prospective study was approved by the institutional review
      board. Written informed consent was obtained from all patients. Fifty-one
      consecutive adult patients with surgically unresectable single or multifocal
      measurable HCC and adequate laboratory parameters who underwent chemoembolization
      in a combined MR imaging-interventional radiology suite between February 2006 and
      June 2010 were studied. Tumor perfusion changes during chemoembolization were
      measured by using TRIP MR imaging with area under the time-signal intensity curve
      calculation. The end point of the study was TFS. The authors assessed the
      correlation between the percentage perfusion reduction in the tumor during
      chemoembolization and TFS by using univariate and multivariate analyses. RESULTS:
      Fifty patients (mean age, 61 years; 39 men aged 42-87 years [mean age, 61 years]
      and 11 women aged 49-83 years [mean age, 62 years]) were eligible for the
      analysis. Patients with 35%-85% intraprocedural tumor area under the time-signal
      intensity curve reduction (n = 32) showed significantly improved median TFS
      compared with patients with an area under the time-signal intensity curve
      reduction outside this range (n = 18) (16.6 months [95% confidence interval:
      11.2, 22.0 months] vs 9.3 months [95% confidence interval: 6.6, 12.0 months],
      respectively; P = .046; hazard ratio: 0.46; 95% confidence interval: 0.21, 1.00).
      The cumulative TFS rates in the 35%-85% and less than 35% or more than 85%
      perfusion reduction groups at 1, 2, and 5 years after chemoembolization were
      66.4%, 42.2%, and 28.2% versus 33.8%, 16.9%, and 0%, respectively. CONCLUSION:
      The study shows evidence of an association between intraprocedural tumor
      perfusion reduction during chemoembolization and TFS and suggests the utility of
      TRIP MR imaging- measured tumor perfusion reduction as an intraprocedural imaging
      biomarker during chemoembolization.

PMID- 24678862
TI  - Evaluation of procedural learning transfer from a virtual environment to a real
      situation: a case study on tank maintenance training.
AB  - Virtual reality opens new opportunities for operator training in complex tasks.
      It lowers costs and has fewer constraints than traditional training. The ultimate
      goal of virtual training is to transfer knowledge gained in a virtual environment
      to an actual real-world setting. This study tested whether a maintenance
      procedure could be learnt equally well by virtual-environment and conventional
      training. Forty-two adults were divided into three equally sized groups: virtual
      training (GVT(r) [generic virtual training]), conventional training (using a real
      tank suspension and preparation station) and control (no training). Participants
      then performed the procedure individually in the real environment. Both training
      types (conventional and virtual) produced similar levels of performance when the
      procedure was carried out in real conditions. Performance level for the two
      trained groups was better in terms of success and time taken to complete the
      task, time spent consulting job instructions and number of times the instructor
      provided guidance. 

PMID- 24678861
TI  - Cytotoxicity of QMixTM endodontic irrigating solution on human bone marrow
      mesenchymal stem cells.
AB  - BACKGROUND: Debridement and disinfection of the root canal system is a crucial
      step in endodontic procedures. The effectiveness of irrigation relies on both the
      mechanical flushing action and the ability of irrigants to dissolve tissue and
      kill bacteria. The objective of the present study is to evaluate and compare the
      cytotoxicity of QMixTM root canal irrigating solution on immortalized human bone
      marrow mesenchymal stem cells (hTERT-MSC-C1) and to compare it with that of
      sodium hypochlorite (NaOCl). METHODS: Immortalized human bone marrow mesenchymal
      stem cells (hTERT-MSCs) were exposed to QMixTM and NaOCl. Cell viability was
      assessed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      and alamarBlue assays. The cell morphology was studied after two hours of
      exposure to QMixTM and NaOCl. Scanning electron microscopy (SEM) analyses were
      performed after 2- and 4-hour incubation periods. Finally, ethidium
      bromide/acridine orange (EB/AO) fluorescent stain was applied to the cells in the
      8-chamber slides after they were incubated with the testing agents for 2 hours to
      detect live and dead cells. The observations were tabulated and analyzed
      statistically. RESULTS: QMixTM exposure resulted in a significantly higher
      percentage of cell viability than NaOCl in the MTT and alamarBlue assays at three
      time points compared to the control. The SEM analysis demonstrated minimal
      morphological changes associated with cells that were exposed to the QMixTM
      solution, with little shrinkage and fragmentation of the cell wall. The live/dead
      analysis showed that the number of live cells after exposure to QMixTM was
      similar to that of the untreated control. No cell structure could be observed
      with the NaOCl group, indicating cell lysis. CONCLUSION: Both the QMixTM and
      NaOCl solutions were toxic to human bone marrow MSCs. Each solution might have
      induced cell death in a different way as evidenced in the cell viability, SEM and
      fluorescent studies. The slower cell death induced by QMixTM might therefore be
      less aggressive and more acceptable to living tissues.

PMID- 24678863
TI  - Environmental and socioeconomic impacts of utilizing waste for biochar in rural
      areas in Indonesia--a systems perspective.
AB  - Biochar is the product of incomplete combustion (pyrolysis) of organic material.
      In rural areas, it can be used as a soil amendment to increase soil fertility.
      Fuel-constrained villagers may however prefer to use biochar briquettes as a
      higher-value fuel for cooking over applying it to soils. A systems-oriented
      analysis using life cycle assessment (LCA) and cost benefit analysis (CBA) was
      conducted to analyze these two alternative uses of biochar, applying the study to
      a rural village system in Indonesia. The results showed soil amendment for
      enhanced agricultural production to be the preferential choice with a positive
      benefit to the baseline scenario of -26 ecopoints (LCA) and -173 USD (CBA)
      annually pr. household. In this case, the positive effects of carbon
      sequestration to the soil and the economic value of the increased agricultural
      production outweighed the negative environmental impacts from biochar production
      and the related production costs. Use of biochar in briquettes for cooking fuel
      yielded negative net effects in both the LCA and CBA (85 ecopoints and 176 USD),
      even when positive health effects from reduced indoor air pollution were
      included. The main reasons for this are that emissions during biochar production
      are not compensated by carbon sequestration and that briquette making is labor
      intensive. The results emphasize the importance of investigating and documenting
      the carbon storage effect and the agricultural benefit in biochar production
      utilization systems for a sustainable use. Further research focus on efficient
      production is necessary due to the large environmental impact of biochar
      production. In addition, biochar should continue to be used in those soils where
      the agricultural effect is most beneficial. 

PMID- 24678864
TI  - Hindsight bias in younger and older adults: the role of access control.
AB  - Hindsight bias is the overestimation of one's earlier knowledge about facts or
      one's prediction of events after learning about the actual facts or events. The
      authors examined age differences in hindsight bias and their relation to visual
      access control. Younger and older adults recalled their numerical answers to
      general-knowledge questions. For half of the items, the correct judgment (CJ) was
      shown during recall. To indicate whether the distracting CJ was visually
      accessed, the authors measured fixations to the CJ. An instructional manipulation
      to ignore the CJ affected fixations and hindsight bias. Older adults showed
      stronger hindsight bias and more fixations to the task-irrelevant CJ, indicating
      an age-related deficit in access control. However, evidence for the effect of CJ
      access on hindsight bias was weak and more pronounced in younger than in older
      adults.

PMID- 24678865
TI  - Commentary: periodontitis is characterized by an immuno-inflammatory host
      mediated destruction of bone and connective tissues that support the teeth.

PMID- 24678866
TI  - Letter to the editor. Re: simplified drilling technique does not decrease dental
      implant osseointegration: a preliminary report.

PMID- 24678867
TI  - Movement sequencing in Huntington disease.
AB  - OBJECTIVES: To examine longitudinal changes in movement sequencing in prodromal
      Huntington's disease (HD) participants (795 prodromal HD; 225 controls) from the
      PREDICT-HD study. METHODS: Prodromal HD participants were tested over seven
      annual visits and were stratified into three groups (low, medium, high) based on
      their CAG-Age Product (CAP) score, which indicates likely increasing proximity to
      diagnosis. A cued movement sequence task assessed the impact of advance cueing on
      response initiation and execution via three levels of advance information.
      RESULTS: Compared to controls, all CAP groups showed longer initiation and
      movement times across all conditions at baseline, demonstrating a disease
      gradient for the majority of outcomes. Across all conditions, the high CAP group
      had the highest mean for baseline testing, but also demonstrated an increase in
      movement time across the study. For initiation time, the high CAP group showed
      the highest mean baseline time across all conditions, but also faster decreasing
      rates of change over time. CONCLUSIONS: With progress to diagnosis, participants
      may increasingly use compensatory strategies, as evidenced by faster initiation.
      However, this occurred in conjunction with slowed execution times, suggesting a
      decline in effectively accessing control processes required to translate movement
      into effective execution.

PMID- 24678869
TI  - The decade of vaccines global vaccine action plan: shaping immunization
      programmes in the current decade.
AB  - Since the establishment of the Expanded Programme on Immunization in 1974, there
      has been considerable progress with scaling up access to immunization globally.
      Currently an estimated 2 to 3 million deaths and an even greater burden of
      morbidity and disability are averted annually through immunization. However, an
      even greater impact can be achieved if the potential of vaccines is fully
      exploited. The Global Vaccine Action Plan (GVAP) provides a framework to make
      life-saving vaccines available to all individuals, regardless of who they are or
      where they live. The first annual progress report of the GVAP noted that while
      there has been progress in several areas, the world is not on track to achieve
      several of the key goals and milestones in the plan. Achieving the vision for the
      decade will require the concerted action of all stakeholders, including national
      governments and communities. 

PMID- 24678870
TI  - Microdebrider use in orbital surgery.
AB  - PURPOSE: To report the novel use of a sinus microdebrider for the removal of
      tissue during orbital surgery. METHODS: This retrospective study reviewed the
      logs of 3 surgeons to identify patients who required orbital surgery during which
      the surgeon chose to use a sinus microdebrider with an open sky technique as a
      means of removing portions of the orbital tissue. Collected data included patient
      demographics, clinical examinations, pathologic diagnoses, radiologic studies,
      operative reports and, when available, photographs and intra-operative video.
      RESULTS: Three patients were identified as having undergone orbital surgery
      assisted by the use of a sinus microdebrider. The first patient had an extensive,
      recurrent left orbital myxoid tumor. Debulking of this gelatinous, infiltrative
      mass was aided by the combined suction and cutting action of the microdebrider.
      Two cases involved orbital exenteration for infiltrative sino-orbital fungus
      infection resulting in a blind eye and frozen globe. Removal of orbital apical
      tissue during exenteration surgery was facilitated with the microdebrider.
      CONCLUSIONS: The characteristics of the sinus microdebrider make it a useful
      adjunct for orbital surgery, particularly in situations where tissue may be
      difficult to grasp and excise. Caution should be exercised whenever using this
      electrically powered tool due to its potential for rapid tissue destruction.
      Therefore, the microdebrider should only be used in cases in which there is
      little risk of damage to essential orbital structures.

PMID- 24678871
TI  - Spontaneous expulsion of lacrimal gland ductule stones by eyelid squeezing: a
      rare event.
AB  - PURPOSE: To report a rare case of lacrimal gland ductule stones. METHODS: Case
      report. RESULTS: A 12-year-old female patient presented with pain, redness and
      swelling in the superotemporal fornix of the left eye of 1-week duration. She had
      experienced four similar episodes over a period of 2 years. Clinical evaluation
      revealed a mass adjacent to the lacrimal gland and some stone edges protruding
      through the lacrimal gland ductules. During preparation for their mechanical
      removal, a spontaneous expulsion of stones occurred. Microbiological examination
      of stones did not show any microorganism or nidus such as cilia. Fourier
      transform infrared spectroscopy revealed the stones to be composed of calcium
      carbonate 90% and magnesium hydrogen phosphates 10%. After spontaneous expulsion,
      the condition subsided without any complications. CONCLUSION: Lacrimal gland
      stones represent a very rare clinical entity and this should be considered in the
      differential diagnosis of recurrent nonspecific conjunctivitis and
      dacryoadenitis.

PMID- 24678868
TI  - Mapping the use of simulation in prehospital care - a literature review.
AB  - BACKGROUND: High energy trauma is rare and, as a result, training of prehospital
      care providers often takes place during the real situation, with the patient as
      the object for the learning process. Such training could instead be carried out
      in the context of simulation, out of danger for both patients and personnel. The
      aim of this study was to provide an overview of the development and foci of
      research on simulation in prehospital care practice. METHODS: An integrative
      literature review were used. Articles based on quantitative as well as
      qualitative research methods were included, resulting in a comprehensive overview
      of existing published research. For published articles to be included in the
      review, the focus of the article had to be prehospital care providers, in
      prehospital settings. Furthermore, included articles must target interventions
      that were carried out in a simulation context. RESULTS: The volume of published
      research is distributed between 1984- 2012 and across the regions North America,
      Europe, Oceania, Asia and Middle East. The simulation methods used were manikins,
      films, images or paper, live actors, animals and virtual reality. The staff
      categories focused upon were paramedics, emergency medical technicians (EMTs),
      medical doctors (MDs), nurse and fire fighters. The main topics of published
      research on simulation with prehospital care providers included: Intubation,
      Trauma care, Cardiac Pulmonary Resuscitation (CPR), Ventilation and Triage.
      CONCLUSION: Simulation were described as a positive training and education method
      for prehospital medical staff. It provides opportunities to train assessment,
      treatment and implementation of procedures and devices under realistic
      conditions. It is crucial that the staff are familiar with and trained on the
      identified topics, i.e., intubation, trauma care, CPR, ventilation and triage,
      which all, to a very large degree, constitute prehospital care. Simulation plays
      an integral role in this. The current state of prehospital care, which this
      review reveals, includes inadequate skills of prehospital staff regarding
      ventilation and CPR, on both children and adults, the lack of skills in
      paediatric resuscitation and the lack of knowledge in assessing and managing
      burns victims. These circumstances suggest critical areas for further training
      and research, at both local and global levels.

PMID- 24678872
TI  - The value of a rate change in determining the tachycardia mechanism: what is the
      mechanism?

PMID- 24678873
TI  - Integration of rural and urban healthcare insurance schemes in China: an
      empirical research.
AB  - BACKGROUND: Despite the broad coverage of the healthcare insurance system in
      China, the imbalances in fairness, accessibility and affordability of healthcare
      services have hindered the universal healthcare progress. To provide better
      financial protection for the Chinese population, China's new medical reform was
      proposed to link up urban employee basic medical insurance scheme (UEBMI), urban
      resident basic medical insurance scheme (URBMI), new rural cooperative medical
      system (NRCMS) and urban and rural medical assistance programs. In this paper, we
      focused on people's expected healthcare insurance model and their willingness
      towards healthcare insurance integration, and we made a couple of relative policy
      suggestions. METHODS: A questionnaire survey was conducted in four cities in
      China. A total of 1178 effective questionnaires were retrieved. Statistical
      analysis was conducted with SPSS and Excel. Chi-square test and logistic
      regression model were applied. RESULTS AND DISCUSSION: The payment intention and
      reimbursement expectation of the three groups varied with NRCMS participants the
      lowest and UEBMI participants the highest. In economic developed areas, rural
      residents had equal or even stronger payment ability than urban residents, and
      the overall payment intention showed a scattered trend; while in less developed
      areas, urban residents had a stronger payment ability than rural residents and a
      more concentrated payment intention was observed. The majority of participants
      favored the integration, with NRCMS enrollees up to 80.5%. In the logistic
      regression model, we found that participants from less developed areas were more
      likely to oppose the integration, which we conceived was mainly due to their
      dissatisfaction with their local healthcare insurance schemes. Also the
      participants with better education background tended to oppose the integration,
      which might be due to their fear of benefit impairment and their concern about
      the challenges ahead. CONCLUSION: Even though there are many challenges for
      healthcare insurance integration, it has received strong support from the mass
      population. However, more emphasis shall be put on equal financing and equal
      benefit when making further policies. As the current healthcare policies share
      the same design concept, principle and method, the ultimate goal of establishing
      a universal healthcare system is promising.

PMID- 24678874
TI  - Special issue: nanotechnology and disease.

PMID- 24678875
TI  - Dynamic remodeling of histone modifications in response to osmotic stress in
      Saccharomyces cerevisiae.
AB  - BACKGROUND: Specific histone modifications play important roles in chromatin
      functions; i.e., activation or repression of gene transcription. This
      participation must occur as a dynamic process. Nevertheless, most of the histone
      modification maps reported to date provide only static pictures that link certain
      modifications with active or silenced states. This study, however, focuses on the
      global histone modification variation that occurs in response to the
      transcriptional reprogramming produced by a physiological perturbation in yeast.
      RESULTS: We did a genome-wide chromatin immunoprecipitation analysis for eight
      specific histone modifications before and after saline stress. The most striking
      change was rapid acetylation loss in lysines 9 and 14 of H3 and in lysine 8 of
      H4, associated with gene repression. The genes activated by saline stress
      increased the acetylation levels at these same sites, but this acetylation
      process was quantitatively minor if compared to that of the deacetylation of
      repressed genes. The changes in the tri-methylation of lysines 4, 36 and 79 of H3
      and the di-methylation of lysine 79 of H3 were slighter than those of
      acetylation. Furthermore, we produced new genome-wide maps for seven histone
      modifications, and we analyzed, for the first time in S. cerevisiae, the genome
      wide profile of acetylation of lysine 8 of H4. CONCLUSIONS: This research reveals
      that the short-term changes observed in the post-stress methylation of histones
      are much more moderate than those of acetylation, and that the dynamics of the
      acetylation state of histones during activation or repression of transcription is
      a much quicker process than methylation.

PMID- 24678877
TI  - Solitary myofibroma of the mandible in an adult with magnetic resonance imaging
      and positron emission tomography findings: a case report.
AB  - Myofibroma is a benign tumor composed of myoid spindle cells. The prevalence of
      myofibroma in the oral cavity is very low, with the mandible being the most
      common site. This report describes an adult case of myofibroma that arose on the
      mandible and includes magnetic resonance imaging (MRI) and positron emission
      tomography (PET) findings. On the MRI T1-weighted images, the tumor appeared with
      signal iso-intensity and was highly and heterogeneously enhanced with contrast
      material. On the T2-weighted images, it appeared with increased signal intensity.
      18 F-fluorodeoxyglucose (FDG)-PET imaging showed abnormal strong accumulation of
      FDG in the left mandibular region. The tumor was removed by marginal resection of
      the left mandible under general anesthesia. Histopathological findings revealed
      that the tumor stroma contained abundant thin-walled vessels. The postoperative
      course was uneventful, and we found no evidence of recurrence at the
      postoperative 34-month follow-up. 

PMID- 24678876
TI  - Calcitriol restores antiestrogen responsiveness in estrogen receptor negative
      breast cancer cells: a potential new therapeutic approach.
AB  - BACKGROUND: Approximately 30% of breast tumors do not express the estrogen
      receptor (ER) alpha, which is necessary for endocrine therapy approaches. Studies
      are ongoing in order to restore ERalpha expression in ERalpha-negative breast
      cancer. The aim of the present study was to determine if calcitriol induces
      ERalpha expression in ER-negative breast cancer cells, thus restoring
      antiestrogen responses. METHODS: Cultured cells derived from ERalpha-negative
      breast tumors and an ERalpha-negative breast cancer cell line (SUM-229PE) were
      treated with calcitriol and ERalpha expression was assessed by real time PCR and
      western blots. The ERalpha functionality was evaluated by prolactin gene
      expression analysis. In addition, the effects of antiestrogens were assessed by
      growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and
      Ether-a-go-go 1 (EAG1) was also evaluated in cells treated with calcitriol alone
      or in combination with estradiol or ICI-182,780. Statistical analyses were
      determined by one-way ANOVA. RESULTS: Calcitriol was able to induce the
      expression of a functional ERalpha in ER-negative breast cancer cells. This
      effect was mediated through the vitamin D receptor (VDR), since it was abrogated
      by a VDR antagonist. Interestingly, the calcitriol-induced ERalpha restored the
      response to antiestrogens by inhibiting cell proliferation. In addition,
      calcitriol-treated cells in the presence of ICI-182,780 resulted in a significant
      reduction of two important cell proliferation regulators CCND1 and EAG1.
      CONCLUSIONS: Calcitriol induced the expression of ERalpha and restored the
      response to antiestrogens in ERalpha-negative breast cancer cells. The combined
      treatment with calcitriol and antiestrogens could represent a new therapeutic
      strategy in ERalpha-negative breast cancer patients.

PMID- 24678879
TI  - [1, 2, 4]-oxadiazoles: synthesis and biological applications.
AB  - In the present article synthesis and medicinal applications of [1, 2, 4]
      oxadiazoles are reviewed. The oxadiazoles have a wide range of applications such
      as Antitussive, Anti-inflammatory, Anaesthetic, Vasodilator, anthelmintic,
      antiallergic, antiplatelet effects in vitro, antithrombotic properties in vivo,
      etc. Many researchers have synthesized novel heterocyclic compounds containing
      oxadiazoles with the concept of bioisosterism. 

PMID- 24678878
TI  - Catalytic asymmetric synthesis of tertiary alkyl fluorides: Negishi cross
      couplings of racemic alpha,alpha-dihaloketones.
AB  - The development of new approaches to the construction of fluorine-containing
      target molecules is important for a variety of scientific disciplines, including
      medicinal chemistry. In this Article, we describe a method for the catalytic
      enantioselective synthesis of tertiary alkyl fluorides through Negishi reactions
      of racemic alpha-halo-alpha-fluoroketones, which represents the first catalytic
      asymmetric cross-coupling that employs geminal dihalides as electrophiles. Thus,
      selective reaction of a C-Br (or C-Cl) bond in the presence of a C-F bond can be
      achieved with the aid of a nickel/bis(oxazoline) catalyst. The products of the
      stereoconvergent cross-couplings, enantioenriched tertiary alpha-fluoroketones,
      can be converted into an array of interesting organofluorine compounds. 

PMID- 24678880
TI  - Update on role of direct renin inhibitor in diabetic kidney disease.
AB  - BACKGROUND: Diabetic kidney disease (DKD) is a leading cause of end-stage renal
      disease (ESRD). Renin-angiotensin-aldosterone system (RAAS) plays a critical role
      in the development of DKD with angiotensin-converting enzyme inhibitors (ACEIs)
      or angiotensin receptor blockers (ARBs) being the mainstay of treatment. Systemic
      RAAS activity has been implicated in the pathogenesis of DKD, but lately interest
      has shifted to intrarenal RAAS effect. With the discovery of the (pro)renin
      receptor and ACE independent pathways of angiotensin II production, our
      understanding of role of renin in end organ damage has improved significantly.
      SUMMARY: We summarize our current understanding of ACE dependent and independent
      pathways in the development of DKD and the preclinical models demonstrating renal
      effects of direct renin inhibitors (DRIs). We then review clinical studies and
      trials performed so far evaluating the efficacy of aliskiren on renal outcomes
      and safety in DKD. KEY MESSAGE: At present, there is little evidence for renal
      benefit of aliskiren in DKD beyond that offered by ACEIs or ARBs. Combining
      aliskiren with ACEI or ARB in DKD did not significantly improve renal outcomes in
      comparison with ACEI or ARB monotherapy in clinical trials. Slightly more adverse
      events including hyperkalemia, acute kidney injury and hypotension were observed
      in the combination therapy as compared to the monotherapy. Thus, current evidence
      suggests that aliskiren, because of its antihypertensive and antiproteinuric
      effects, maybe used as monotherapy in DKD and considered an equivalent
      alternative to ACEIs or ARBs. Careful monitoring for renal adverse effects would
      allow safe clinical use of DRI.

PMID- 24678882
TI  - Discrimination of fennel chemotypes applying IR and Raman spectroscopy: discovery
      of a new gamma-asarone chemotype.
AB  - Various vibrational spectroscopy methods have been applied to classify different
      fennel chemotypes according to their individual profile of volatile substances.
      Intact fennel fruits of different chemotypes could be successfully discriminated
      by attenuated total reflectance Fourier transform infrared (ATR-FTIR) and near
      infrared (NIR) spectroscopy. Solvent extracts (CCl4) of the considered fennel
      fruits showed characteristic fingerprints with marker bands related to the
      individual volatile components (trans-anethole, fenchone, estragole, piperitenone
      oxide, gamma-asarone, limonene) for ATR-FTIR and FT-Raman spectroscopy.
      Especially nuC?C and nuC?O absorption bands contribute to the different spectral
      profiles. On the basis of hierarchical cluster analysis, the considered fennel
      accessions were classified according to gas chromatographic (GC) and vibrational
      spectroscopic data. Furthermore, even a discrimination of "sweet" and "bitter"
      fennel fruits, both belonging to the trans-anethole chemotype, could be
      successfully performed. All vibrational spectroscopical techniques used in this
      study are rapid and easy to apply. Hence, they allow different fennel chemotypes
      to be reliably distinguished and can also be used for on-site measurement in free
      nature. 

PMID- 24678883
TI  - Theoretical studies of structures and vibrational sum frequency generation
      spectra at aqueous interfaces.

PMID- 24678881
TI  - The extracellular matrix in the kidney: a source of novel non-invasive biomarkers
      of kidney fibrosis?
AB  - Interstitial fibrosis is the common endpoint of end-stage chronic kidney disease
      (CKD) leading to kidney failure. The clinical course of many renal diseases, and
      thereby of CKD, is highly variable. One of the major challenges in deciding which
      treatment approach is best suited for a patient but also in the development of
      new treatments is the lack of markers able to identify and stratify patients with
      stable versus progressive disease. At the moment renal biopsy is the only means
      of diagnosing renal interstitial fibrosis. Novel biomarkers should improve
      diagnosis of a disease, estimate its prognosis and assess the response to
      treatment, all in a non-invasive manner. Existing markers of CKD do not fully and
      specifically address these requirements and in particular do not specifically
      reflect renal fibrosis. The aim of this review is to give an insight of the
      involvement of the extracellular matrix (ECM) proteins in kidney diseases and as
      a source of potential novel biomarkers of renal fibrosis. In particular the use
      of the protein fingerprint technology, that identifies neo-epitopes of ECM
      proteins generated by proteolytic cleavage by proteases or other post
      translational modifications, might identify such novel biomarkers of renal
      fibrosis. 

PMID- 24678884
TI  - Recognition of change in the reform of forensic mental health by clinical
      practitioners: a questionnaire survey in Japan.
AB  - In Japan, new legislation regarding forensic mental health, namely, the Act on
      Medical Care and Treatment for Persons Who Have Caused Serious Cases under the
      Condition of Insanity (Medical Treatment and Supervision Act (MTS Act)) was
      enforced in 2005, although community mental health care remains largely
      unchanged. We surveyed local clinical psychiatrists by questionnaire to gather
      information on the influence of the MTS Act on clinical mental health practice.
      We sent a paper questionnaire to almost all the psychiatrists in the Chiba
      prefecture, 56% of whom (N = 306) responded. The participants felt that the MTS
      Act had minimal direct impact on community mental health care. However, some
      relatively new schemes such as a multiple disciplinary team approach or
      supervised outpatient care are given more attention than before. These results
      suggest that this new forensic mental health legislation may assist in the spread
      of new paradigms into clinical practice. 

PMID- 24678885
TI  - Far-infrared graphene plasmonic crystals for plasmonic band engineering.
AB  - We introduce far-infrared graphene plasmonic crystals. Periodic structural
      perturbation-in a proof-of-concept form of hexagonal lattice of apertures-of a
      continuous graphene medium alters delocalized plasmonic dynamics, creating
      plasmonic bands in a manner akin to photonic crystals. Fourier transform infrared
      spectroscopy demonstrates band formation, where far-infrared irradiation excites
      a unique set of plasmonic bands selected by phase matching and symmetry-based
      selection rules. This band engineering may lead to a new class of graphene
      plasmonic devices. 

PMID- 24678886
TI  - Four polymorphisms of VEGF (+405C>G, -460T>C, -2578C>A, and -1154G>A) in
      susceptibility to psoriasis: a meta-analysis.
AB  - The contribution of genetic polymorphisms in the vascular endothelial growth
      factor (VEGF) gene to psoriasis risk is a controversial topic. The aim of this
      meta-analysis was to investigate large-scale evidence to determine the degree to
      which four common VEGF polymorphisms (+405C>G [dbSNP: rs2010963], -460T>C [dbSNP:
      rs833061], -2578C>A [dbSNP: rs699947], and -1154G>A [dbSNP: rs1570360]) are
      associated with susceptibility to psoriasis. A literature search of PubMed,
      Embase, Web of Science, Chinese National Knowledge Infrastructure, and Chinese
      Biomedical Literature Database was conducted to identify all eligible studies
      published before September 15, 2013. The principal outcome measure for evaluating
      the strength of the association was crude odds ratios (ORs) along with their
      corresponding 95% confidence intervals (95% CIs). Two thousand five hundred
      thirty-one patients and 2670 controls from nine case-control studies detailing a
      possible association between the VEGF genotypes and psoriasis risk were selected.
      Our meta-analysis provides evidence that two independent alleles +405G and -460C
      may be a protective factor for psoriasis in Asians, whereas the -1154A allele had
      a slight but statistically significant preventive effect on the development of
      psoriasis in Caucasians. The -2578C>A polymorphism, however, did not correlate
      with any significant difference between patients and healthy controls, even when
      the groups were stratified by ethnicity. Results from the meta-analysis do
      support the hypothesis that single-nucleotide polymorphism markers at +405C>G, 
      460C>T, and -1154G>A of the VEGF gene may serve as biological markers of
      psoriasis. Future studies should investigate interactions among multiple
      genotypes and environmental exposures to identify the role of proangiogenic
      markers in psoriasis and to delineate the underlying mechanisms of psoriasis. 

PMID- 24678887
TI  - Medical prevention of recurrent acute otitis media: an updated overview.
AB  - Acute otitis media (AOM) is one of the most common pediatric diseases; almost all
      children experience at least one episode, and a third have two or more episodes
      in the first three years of life. The disease burden of AOM has important
      medical, social and economic effects. AOM requires considerable financial
      assistance due to needing at least one doctor visit and a prescription for
      antipyretics and/or antibiotics. AOM is also associated with high indirect costs,
      which are mostly related to lost days of work for one parent. Moreover, due to
      its acute symptoms and frequent recurrences, AOM considerably impacts both the
      child and family's quality of life. AOM prevention, particularly recurrent AOM
      (rAOM), is a primary goal of pediatric practice. In this paper, we review current
      evidence regarding the efficacy of medical treatments and vaccines for preventing
      rAOM and suggest the best approaches for AOM-prone children. 

PMID- 24678888
TI  - Quantitative metabolite profiling utilizing parallel column analysis for
      simultaneous reversed-phase and hydrophilic interaction liquid chromatography
      separations combined with tandem mass spectrometry.
AB  - In this work, a fully automated parallel LC column method was established in
      order to perform orthogonal hydrophilic interaction chromatography (HILIC) and
      reversed-phase (RPLC) chromatography within one analytical run for targeted
      quantitative mass spectrometric determination of metabolites from central carbon
      metabolism. In this way, the analytical throughput could be significantly
      improved compared to previously established dual separation work flows involving
      two separate analytical runs. Two sample aliquots were simultaneously injected
      onto a dual column setup columns using a ten-port valve, and parallel separations
      were carried out. Sub 2 MUm particle size stationary phases were employed for
      both separation methods. HILIC and RPLC eluents were combined post column
      followed by ESI-MS/MS detection. The orthogonal separations were optimized,
      aiming at an overall separation with 2 retention time segments, while reversed
      phase separation was accomplished within 5.5 min; metabolites on the HILIC phase
      were retained for a minimum time of 6 min. The overall run time was 15 min. The
      setup was applied to the quantification of 30 primary intercellular metabolites,
      including amino acids, organic acids, and nucleotides employing internal
      standardization by a fully (13)C-labeled yeast extract. The comparison with HILIC
      MS/MS and RPLC-MS/MS in separate analytical runs revealed that an excellent
      analytical performance was achieved by the parallel LC column method. The
      experimental repeatability (N = 5) was on average <5% (only for 2 compounds >5%).
      Moreover, limits of detection for the new approach ranging from 0.002-15 MUM were
      in a good agreement with ones obtained in separate HILIC-MS/MS and RPLC-MS/MS
      runs (ranging from 0.01-44 MUM). 

PMID- 24678889
TI  - Femoral neck shaft angle width is associated with hip-fracture risk in males but
      not independently of femoral neck bone density.
AB  - OBJECTIVE: To investigate the specificity of the neck shaft angle (NSA) to
      predict hip fracture in males. METHODS: We consecutively studied 228 males
      without fracture and 38 with hip fracture. A further 49 males with spine fracture
      were studied to evaluate the specificity of NSA for hip-fracture prediction.
      Femoral neck (FN) bone mineral density (FN-BMD), NSA, hip axis length and FN
      diameter (FND) were measured in each subject by dual X-ray absorptiometry.
      Between-mean differences in the studied variables were tested by the unpaired t
      test. The ability of NSA to predict hip fracture was tested by logistic
      regression. RESULTS: Compared with controls, FN-BMD (p < 0.01) was significantly
      lower in both groups of males with fractures, whereas FND (p < 0.01) and NSA (p =
      0.05) were higher only in the hip-fracture group. A significant inverse
      correlation (p < 0.01) was found between NSA and FN-BMD. By age-, height- and
      weight-corrected logistic regression, none of the tested geometric parameters,
      separately considered from FN-BMD, entered the best model to predict spine
      fracture, whereas NSA (p < 0.03) predicted hip fracture together with age (p <
      0.001). When forced into the regression, FN-BMD (p < 0.001) became the only
      fracture predictor to enter the best model to predict both fracture types.
      CONCLUSION: NSA is associated with hip-fracture risk in males but is not
      independent of FN-BMD. ADVANCES IN KNOWLEDGE: The lack of ability of NSA to
      predict hip fracture in males independent of FN-BMD should depend on its inverse
      correlation with FN-BMD by capturing, as the strongest fracture predictor, some
      of the effects of NSA on the hip fracture. Conversely, NSA in females does not
      correlate with FN-BMD but independently predicts hip fractures.

PMID- 24678890
TI  - Decreased expression of eukaryotic initiation factor 3f is an adverse prognostic
      factor for stage I-III gastric cancer.
AB  - BACKGROUND: It has been demonstrated that eIF3f expression is significantly
      decreased in many human cancers, a fact which plays an important role in human
      cancer. However, the expression of eIF3f in gastric cancer (GC) is not well
      understood to date. Therefore, the aim of this study is to detect the expression
      of eIF3f in GC. METHODS: The expression of eIF3f was examined by
      immunohistochemistry in tissues with stage I to III GC and adjacent non-cancerous
      tissues (ANCT) of 195 gastrectomy specimens; clinicopathological results,
      including survival, were analyzed. RESULTS: The positive expression rate of eIF3f
      was significantly higher in ANCT tissues than in GC. eIF3f levels were correlated
      with more advanced tumor stages and likelihood of recurrence (all P<0.05). The
      Kaplan-Meier survival curves indicated that decreased expression of eIF3f could
      serve as a prognosis marker for poor outcome of GC patients (P=0.04).
      CONCLUSIONS: eIF3f may play an important role in recurrence, thus representing a
      promising predictive marker for the prognosis of GC.

PMID- 24678891
TI  - Fish mercury levels appear to be increasing lately: a report from 40 years of
      monitoring in the province of Ontario, Canada.
AB  - Recent mercury levels and trends reported for North America suggest a mixed
      (positive/negative) outlook for the environmental mercury problem. Using one of
      the largest consistent monitoring data sets in the world, here we present long
      term and recent mercury trends in Walleye, Northern Pike, and Lake Trout from the
      Province of Ontario, Canada, which contains about one-third of the world's fresh
      water and covers a wide geographical area (1.5 and 3 times larger than France and
      Germany, respectively). Overall, the results indicate that the fish mercury
      levels either declined (0.01-0.07 MUg/g decade) or remained stable between the
      1970s and 2012. The rates of mercury decline were substantially greater (mostly
      0.05-0.31 MUg/g decade) during the 1970s/80s possibly in response to reductions
      in mercury emissions. However, Walleye and Pike levels have generally increased
      (0.01-0.27 MUg/g decade) in recent years (1995-2012), especially for northern
      Ontario (effect sizes for differences between the two periods ranged from 0.39 to
      1.04). Proportions of Walleye and Pike locations showing a flat or increasing
      trend increased from 26-44% to 59-73% between the 1970s/80s and 1995-2012.
      Mercury emissions in North America have declined over the last few decades, and
      as such it is logical to expect recovery in fish mercury levels; however, other
      factors such as global emissions, climate change, invasive species, and local
      geochemistry are likely affecting the response time and magnitude. 

PMID- 24678893
TI  - Moving beyond "sticks and stones": chronic psychological trauma predicts
      posttraumatic stress symptoms.
AB  - To date, trauma research has focused on the impact of physical trauma on
      posttraumatic stress (PTS) symptoms. Sometimes psychological trauma is measured
      with instances of physical trauma; however, less is known about solely
      psychological trauma. The current study addresses this by examining psychological
      trauma and PTS symptoms using the chronic relational trauma (CRT) model. The CRT
      model examines physical and possible concurrent psychological childhood, peer,
      and intimate partner trauma; however, psychological trauma alone has yet to be
      tested. A total of 232 female undergraduates (M age = 18.32, SD = 1.60) completed
      a series of questionnaires. Structural equation modeling indicated that
      childhood, peer, and intimate partner psychological trauma predict current PTS
      symptoms. Contributions of these findings are discussed. 

PMID- 24678892
TI  - Effect of different preventive agents on bracket shear bond strength: in vitro
      study.
AB  - BACKGROUND: The effects of fluoride and CPP-ACP before bracket bonding on the
      shear bond strength of orthodontic brackets have been reported with contradicting
      results. The objective of this in vitro study was to evaluate the effect of
      different preventive agents namely; casein phosphopeptide-amorphous-calcium
      phosphate (CPP-ACP), fluoride-containing-CPP-ACP (CPP-ACPF) and 5% sodium
      fluoride (5% NaF), on the enamel-bracket shear bond strength (SBS) and to compare
      their effects when applied before or after acid-etching. METHODS: Human premolar
      teeth were randomly divided into seven groups (16 teeth per group) as follows:
      the control group, where no preventive agent was applied on the enamel and 6
      experimental groups. Teeth in groups 1a, 2a, and 3a were treated with CPP-ACP
      paste, CPP-ACPF paste, and 5% NaF, respectively before acid-etching. Teeth in
      groups 1b, 2b and 3b were treated using the same preventive agents after acid
      etching. The brackets were then bonded and the teeth were thermocycled. The
      brackets' SBS was measured and the adhesive remnant was assessed using adhesive
      remnant index (ARI). Analysis of variance (ANOVA) and Tukey test were performed
      to compare the SBS among different groups. Chi-square test was used to evaluate
      differences in ARI scores between the groups. RESULTS: Enamel surface treatment
      with CPP-ACPF after acid-etching significantly increased SBS compared to the
      control and to its application before acid-etching (P < 0.05). Higher ARI index
      was recorded when the preventive agents were applied after acid-etching.
      CONCLUSION: Brackets' SBS significantly increased when fluoride-containing-CPP
      ACP was applied after acid-etching.

PMID- 24678895
TI  - Could resveratrol be a useful drug for the treatment of malignant hemopathies?
AB  - Resveratrol is a poly-phenol with many beneficial effects: not only as an
      antioxidant, anti-inflammatory, and antiatherogenic agent, as well as a platelet
      aggregation inhibitor, but also as an antiproliferative and proapoptotic factor
      in various types of cancers. There are reviews about the mechanisms responsible
      for its effects in leukemia and lymphomas, emphasizing the chemosensitizing role
      of resveratrol, which allows overcoming the multidrug resistance of cancers. The
      action of resveratrol occurs preferentially on leukemic cells, and not on the
      normal ones. In addition, it is one of the few drugs that act on leukemic stem
      cells. If experimental results are promising, its application in humans
      encounters some difficulties. The paper presents the causes of its low
      bioavailability, as well as recent patents that allow improvement of its
      bioavailability, development of new extraction procedures, obtaining new
      formulae, and associating resveratrol with other drugs in order to increase its
      effects. These patents allow optimizing its effects in order to obtain an
      adjuvant agent for treatment of oncohematological disorders. 

PMID- 24678894
TI  - Identification of biomarkers that distinguish chemical contaminants based on gene
      expression profiles.
AB  - BACKGROUND: High throughput transcriptomics profiles such as those generated
      using microarrays have been useful in identifying biomarkers for different
      classification and toxicity prediction purposes. Here, we investigated the use of
      microarrays to predict chemical toxicants and their possible mechanisms of
      action. RESULTS: In this study, in vitro cultures of primary rat hepatocytes were
      exposed to 105 chemicals and vehicle controls, representing 14 compound classes.
      We comprehensively compared various normalization of gene expression profiles,
      feature selection and classification algorithms for the classification of these
      105 chemicals into14 compound classes. We found that normalization had little
      effect on the averaged classification accuracy. Two support vector machine (SVM)
      methods, LibSVM and sequential minimal optimization, had better classification
      performance than other methods. SVM recursive feature selection (SVM-RFE) had the
      highest overfitting rate when an independent dataset was used for a prediction.
      Therefore, we developed a new feature selection algorithm called gradient method
      that had a relatively high training classification as well as prediction accuracy
      with the lowest overfitting rate of the methods tested. Analysis of biomarkers
      that distinguished the 14 classes of compounds identified a group of genes
      principally involved in cell cycle function that were significantly downregulated
      by metal and inflammatory compounds, but were induced by anti-microbial, cancer
      related drugs, pesticides, and PXR mediators. CONCLUSIONS: Our results indicate
      that using microarrays and a supervised machine learning approach to predict
      chemical toxicants, their potential toxicity and mechanisms of action is
      practical and efficient. Choosing the right feature and classification algorithms
      for this multiple category classification and prediction is critical.

PMID- 24678897
TI  - Mixed layers of beta-lactoglobulin and SDS at air-water interfaces with tunable
      intermolecular interactions.
AB  - Mixtures of beta-lactoglobulin (BLG) and sodium dodecyl sulfate (SDS) were
      studied at pH 3.8 and 6.7 under equilibrium conditions. At these pH conditions,
      BLG carries either a positive or a negative net charge, respectively, which
      enables tunable electrostatic interactions between anionic SDS surfactants and
      BLG proteins. For pH 3.8, vibrational sum-frequency generation (SFG) and
      ellipsometry indicate strong BLG-SDS complex formation at air-water interfaces
      that is caused by attractive electrostatic interactions. The latter complexes are
      already formed in the bulk solution which was confirmed by a thermodynamic study
      of BLG-SDS mixtures using isothermal titration calorimetry (ITC). For acidic
      conditions we determine from our ITC data an exothermal binding enthalpy of -40
      kJ mol(-1). Increasing SDS/BLG molar ratios above 10 leads to a surface excess of
      SDS and thus to a charge reversal from a positive net charge with BLG as the
      dominating surface adsorbed species to a negatively charged layer with SDS as the
      dominating surface species. The latter is evidenced by a pronounced minimum in
      SFG intensities that is also accompanied by a phase change of O-H stretching
      bands due to a reorientation of H2O within the local electric field. This phase
      change which occurs at SDS/BLG molar ratio between 1 and 10 causes a polarity
      change in SFG intensities from BLG aromatic C-H stretching vibrations.
      Conclusions from SFG spectra are corroborated by ellipsometry which shows a
      dramatic increase in layer thicknesses at molar ratios where a charge reversal
      occurs. The formation of interfacial multilayers comprising SDS-BLG complexes is,
      thus, caused by cancellation of electrostatic interactions which leads to
      agglomeration at the interface. In contrast to pH 3.8, behavior of BLG-SDS
      mixtures at pH 6.7 is different due to repulsive electrostatic interactions
      between SDS and BLG which lead to a significantly reduced binding enthalpy of -17
      kJ mol(-1). Finally, it has to be mentioned that SFG spectra show a coexistence
      of BLG and SDS molecules at the interface for BLG-SDS molar ratios > 2. 

PMID- 24678896
TI  - Population screening for colorectal cancer by flexible sigmoidoscopy or CT
      colonography: study protocol for a multicenter randomized trial.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most prevalent type of cancer
      in Europe. A single flexible sigmoidoscopy (FS) screening at around the age of 60
      years prevents about one-third of CRC cases. However, FS screens only the distal
      colon, and thus mortality from proximal CRC is unaffected. Computed tomography
      colonography (CTC) is a highly accurate examination that allows assessment of the
      entire colon. However, the benefit of CTC testing as a CRC screening test is
      uncertain. We designed a randomized trial to compare participation rate,
      detection rates, and costs between CTC (with computer-aided detection) and FS as
      primary tests for population-based screening. METHODS/DESIGN: An invitation
      letter to participate in a randomized screening trial comparing CTC versus FS
      will be mailed to a sample of 20,000 people aged 58 or 60 years, living in the
      Piedmont region and the Verona district of Italy. Individuals with a history of
      CRC, adenomas, inflammatory bowel disease, or recent colonoscopy, or with two
      first-degree relatives with CRC will be excluded from the study by their general
      practitioners. Individuals responding positively to the invitation letter will be
      then randomized to the intervention group (CTC) or control group (FS), and
      scheduled for the screening procedure. The primary outcome parameter of this part
      of the trial is the difference in advanced neoplasia detection between the two
      screening tests. Secondary outcomes are cost-effectiveness analysis, referral
      rates for colonoscopy induced by CTC versus FS, and the expected and perceived
      burden of the procedures. To compare participation rates for CTC versus FS, 2,000
      additional eligible subjects will be randomly assigned to receive an invitation
      for screening with CTC or FS. In the CTC arm, non-responders will be offered
      fecal occult blood test (FOBT) as alternative screening test, while in the FS
      arm, non-responders will receive an invitation letter to undergo screening with
      either FOBT or CTC. Data on reasons for participation and non-participation will
      also be collected. DISCUSSION: This study will provide reliable information
      concerning benefits and risks of the adoption of CTC as a mass screening
      intervention in comparison with FS. The trial will also evaluate the role of
      computer-aided detection in a screening setting. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT01739608.

PMID- 24678898
TI  - Predictors of default from follow-up care in a cervical cancer screening program
      using direct visual inspection in south-western Nigeria.
AB  - BACKGROUND: Increasingly evidence is emerging from south East Asia, southern and
      east Africa on the burden of default to follow up care after a positive cervical
      cancer screening/diagnosis, which impacts negatively on cervical cancer
      prevention and control. Unfortunately little or no information exists on the
      subject in the West Africa sub region. This study was designed to determine the
      proportion of and predictors and reasons for default from follow up care after
      positive cervical cancer screen. METHOD: Women who screen positive at community
      cervical cancer screening using direct visual inspection were followed up to
      determine the proportion of default and associated factors. Multivariate logistic
      regression was used to determine independent predictors of default. RESULTS: One
      hundred and eight (16.1%) women who screened positive to direct visual inspection
      out of 673 were enrolled into the study. Fifty one (47.2%) out of the 108 women
      that screened positive defaulted from follow-up appointment. Women who were
      poorly educated (OR: 3.1, CI: 2.0 - 5.2), or lived more than 10 km from the
      clinic (OR: 2.0, CI: 1.0 - 4.1), or never screened for cervical cancer before
      (OR: 3.5, CI:3:1-8.4) were more likely to default from follow-up after screening
      positive for precancerous lesion of cervix . The main reasons for default were
      cost of transportation (48.6%) and time constraints (25.7%). CONCLUSION: The rate
      of default was high (47.2%) as a result of unaffordable transportation cost and
      limited time to keep the scheduled appointment. A change from the present
      strategy that involves multiple visits to a "see and treat" strategy in which
      both testing and treatment are performed at a single visit is recommended.

PMID- 24678899
TI  - Negative association between plasma aldosterone concentration/plasma renin
      activity and morning blood pressure surge in never-treated hypertensive patients.
AB  - Morning blood pressure (BP) surge (MS) has been known to be a predictor of
      cardiovascular events. Currently, few studies have evaluated the underlying
      mechanism underlying MS, which may include neurohormonal factors and the renin
      angiotensin-aldosterone system (RAAS). This study aimed to examine plasma
      aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters
      with or without MS in never-treated subjects with essential hypertension. This
      cross-sectional study included a total of 261 patients (mean age: 48.8 years;
      60.5% male) with never-treated essential hypertension who were registered in a
      working group at The Catholic University of Korea. The patients were divided into
      the MS group, which was defined as having the highest quartile of morning BP
      increase from sleep (>31 mmHg; n = 66) and the non-MS group (<=31 mmHg; n = 195).
      We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC
      and PRA from all patients. The measured PAC and PRA were lower in the MS group
      than in the non-MS group (PAC: 9.0 +/- 5.4 ng/dl versus 12.2 +/- 8.7 ng/dl, p <
      0.001; PRA: 1.7 +/- 1.3 ng/ml/h versus 2.6 +/- 3.6 ng/ml/h, p = 0.002). The MS
      group had greater variations in daytime, nighttime and 24-h systolic blood
      pressure (SBPs) than the non-MS group (24-h SBP: 15.6 +/- 4.4 mm Hg for the non
      MS group and 18.9 +/- 4.9 mmHg for the MS group; p < 0.001 for each). It is
      generally accepted that the sympathetic nervous system plays a major role in the
      regulation of BP variability. Therefore, further studies on sympathetic nervous
      system activation in hypertensives with extreme MS are needed. MS in enrolled
      patients who were at relatively low risk in this study may be less affected by
      the RAAS.

PMID- 24678901
TI  - Coaxial multishell (In,Ga)As/GaAs nanowires for near-infrared emission on Si
      substrates.
AB  - Efficient infrared light emitters integrated on the mature Si technology platform
      could lead to on-chip optical interconnects as deemed necessary for future
      generations of ultrafast processors as well as to nanoanalytical functionality.
      Toward this goal, we demonstrate the use of GaAs-based nanowires as building
      blocks for the emission of light with micrometer wavelength that are
      monolithically integrated on Si substrates. Free-standing (In,Ga)As/GaAs coaxial
      multishell nanowires were grown catalyst-free on Si(111) by molecular beam
      epitaxy. The emission properties of single radial quantum wells were studied by
      cathodoluminescence spectroscopy and correlated with the growth kinetics.
      Controlling the surface diffusivity of In adatoms along the NW side-walls, we
      improved the spatial homogeneity of the chemical composition along the nanowire
      axis and thus obtained a narrow emission spectrum. Finally, we fabricated a light
      emitting diode consisting of approximately 10(5) nanowires contacted in parallel
      through the Si substrate. Room-temperature electroluminescence at 985 nm was
      demonstrated, proving the great potential of this technology. 

PMID- 24678900
TI  - Spontaneous and adenosine-induced pulmonary vein reconnection after cryoballoon
      ablation with the second-generation device.
AB  - INTRODUCTION: Longer observational time and adenosine challenge have proven to be
      able to detect pulmonary vein (PV) reconnections. The aim of this study was to
      assess incidence of spontaneous and adenosine-induced PV reconnection after
      ablation with second-generation cryoballoon (CB-Adv). METHODS AND RESULTS: Fifty
      consecutive patients (76% male, mean age 60.5 +/- 11.9 years) having undergone PV
      isolation (PVI) using the CB-Adv were enrolled. After isolation, reconnections
      were evaluated using the Achieve catheter over 30 minutes observation and
      adenosine administration during isoproterenol infusion (adenosine challenge).
      Among 200 PVs, isolation was achieved in 190 (95%) during the first application.
      Lower nadir temperature and longer rewarming time were associated with successful
      PVI (P = 0.02 and 0.04). Spontaneous (4 veins) and adenosine-induced (4 veins) PV
      reconnections occurred in the 4% of initially isolated veins (8 veins) in 6
      patients (12%). At receiver-operator curve analysis, nadir temperature <-51 
      degrees C and rewarming time >28 seconds identified absence of reconnections
      (sensitivity 100% and 87%, area under the curve 0.75 and 0.72). Patients with
      right-sided early branching frequently experienced reconnections (P < 0.01).
      After a mean follow-up of 7.0 +/- 1.7 months, 86% of patients were free from
      atrial fibrillation. None of those with PV reconnections experienced recurrences.
      CONCLUSIONS: The incidence of spontaneous and adenosine-induced PV reconnection
      following ablation with the novel CB-Adv is very low occurring in 4% of initially
      isolated veins. Nadir temperature <-51  degrees C and rewarming time >28 seconds
      identified absence of acute reconnections, thus avoiding prolonged waiting time
      and adenosine challenge in such cases.

PMID- 24678902
TI  - A phase II study of cisplatin with intravenous and oral vinorelbine as induction
      chemotherapy followed by concomitant chemoradiotherapy with oral vinorelbine and
      cisplatin for locally advanced non-small cell lung cancer.
AB  - BACKGROUND: Concomitant platinum-based chemotherapy and radiotherapy (CT-RT) is
      the recommended treatment for unresectable locally advanced stage III non-small
      cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy
      and safety of fractionated oral vinorelbine with cisplatin as induction CT
      followed by CT-RT. METHODS: Patients with stage III NSCLC received 2 induction
      cycles of intravenous vinorelbine 25 mg/m2 and cisplatin 80 mg/m2 on day 1 and
      oral vinorelbine 60 mg/m2 on day 8. Responding patients received 2 more cycles of
      cisplatin 80 mg/m2 on day 1 and oral vinorelbine 20 mg on days 1, 3 and 5
      concomitantly with radiotherapy 2 Gy daily, 5 days/week for a total of 66 Gy.
      RESULTS: Seventy patients, median age 61 years, were enrolled. Overall response
      rate (ORR) was 50.0%; Disease Control Rate was 81.42%. Median PFS was 14.58
      months [95% CI, 10.97-18.75]. Median OS was 17.08 months [95% CI, 13.57-29.57].
      One-year and 2-year survival rates were 68.6% [95% CI, 57.7-79.4] and 37%. One
      patient had a grade 3 pulmonary radiation injury and 26.5% had graded 1/2
      esophagitis. CONCLUSION: In non-operable IIIA-IIIB NSCLC, the combination oral
      vinorelbine (fractionated fixed dose) plus cisplatin, during concomitant CT-RT,
      could offer a well-tolerated option, with comparable activity to I.V. vinorelbine
      based chemoradiotherapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01839032.

PMID- 24678904
TI  - Clinical characteristics of second primary cancer in colorectal cancer patients:
      the impact of colorectal cancer or other second cancer occurring first.
AB  - BACKGROUND: Due to improvements in early detection, treatment, and supportive
      care, the number of colorectal cancer (CRC) survivors is increasing; therefore,
      careful attention should always be paid to the second primary cancer (SPC) in
      treating these CRC patients. The present study attempts to determine the
      correlation and clinical aspects of CRC to other cancers in patients suffering
      from SPC involving CRC. METHODS: From January 2002 and June 2010, 1,679 cancer
      cases, CRC was accompanied by SPC in 89 patients (5.3%), including 16 (18%)
      synchronous and 73 (82%) metachronous SPC patients. These patients were
      subsequently classified into two groups: the first group had CRC diagnosed first
      as CRC first (CRCF); and the second group had another type of cancer diagnosed
      before the diagnosis of CRC as other cancer first (OCF). Of these 73 patients, 22
      (30.1%) were in the group of CRCF, whereas 51 (69.9%) were in the group of OCF.
      Patients' clinicopathological characteristics and clinical outcomes were analyzed
      and compared between the two groups. RESULTS: There was a significant difference
      in the sites of cancers between the two groups: 14 (27.5%) patients in the OCF
      group had gastric cancer, compared to one (4.5%) patient in the CRCF group (P =
      0.026). Although there was no difference of hepatitis B virus (HBV) or hepatitis
      C virus (HCV) carriers between the OCF and CRCF groups (P = 0.165), there were
      six (27.3%) CRC patients with hepatocellular carcinoma (HCC) in the CRCF group,
      which was significantly higher than the two (3.9%) patients in the OCF group (P =
      0.003). Furthermore, the cancer-specific survival rate of the CRCF patient group
      was significantly higher than that of the OCF patient group (P = 0.036).
      CONCLUSIONS: In this retrospective analysis, gastric cancer patients compared to
      other secondary cancers were at a higher risk of developing subsequent CRC as
      SPC; alternatively, patients with CRC were at a higher risk of developing HCC as
      SPC subsequently, no matter whether patients were HBV or HCV carriers. Therefore,
      careful attention should always be paid to the possibility of secondary CRC to
      construct effective surveillance when treating cancer patients.

PMID- 24678905
TI  - Synthesis and applications of vinylaziridines and ethynylaziridines.

PMID- 24678903
TI  - Medical therapy of stricturing Crohn's disease: what the gut can learn from other
      organs - a systematic review.
AB  - Crohn's disease (CD) is a chronic remitting and relapsing disease. Fibrostenosing
      complications such as intestinal strictures, stenosis and ultimately obstruction
      are some of its most common long-term complications. Despite recent advances in
      the pathophysiological understanding of CD and a significant improvement of anti
      inflammatory therapeutics, medical therapy for stricturing CD is still
      inadequate. No specific anti-fibrotic therapy exists and the incidence rate of
      strictures has essentially remained unchanged. Therefore, the current therapy of
      established fibrotic strictures comprises mainly endoscopic dilation as well as
      surgical approaches. However, these treatment options are associated with major
      complications as well as high recurrence rates. Thus, a specific anti-fibrotic
      therapy for CD is urgently needed. Importantly, there is now a growing body of
      evidence for prevention as well as effective medical treatment of fibrotic
      diseases of other organs such as the skin, lung, kidney and liver. In face of the
      similarity of molecular mechanisms of fibrogenesis across these organs,
      translation of therapeutic approaches from other fibrotic diseases to the
      intestine appears to be a promising treatment strategy. In particular
      transforming growth factor beta (TGF-beta) neutralization, selective tyrosine
      kinase inhibitors, blockade of components of the renin-angiotensin system, IL-13
      inhibitors and mammalian target of rapamycin (mTOR) inhibitors have emerged as
      potential drug candidates for anti-fibrotic therapy and may retard progression or
      even reverse established intestinal fibrosis. However, major challenges have to
      be overcome in the translation of novel anti-fibrotics into intestinal fibrosis
      therapy, such as the development of appropriate biomarkers that predict the
      development and accurately monitor therapeutic responses. Future clinical studies
      are a prerequisite to evaluate the optimal timing for anti-fibrotic treatment
      approaches, to elucidate the best routes of application, and to evaluate the
      potential of drug candidates to reach the ultimate goal: the prevention or
      reversal of established fibrosis and strictures in CD patients. 

PMID- 24678906
TI  - Efficacy and safety of monotherapy with the novel sodium/glucose cotransporter-2
      inhibitor tofogliflozin in Japanese patients with type 2 diabetes mellitus: a
      combined Phase 2 and 3 randomized, placebo-controlled, double-blind, parallel
      group comparative study.
AB  - BACKGROUND: In recent years, several oral antidiabetic drugs with new mechanisms
      of action have become available, expanding the number of treatment options.
      Sodium/glucose cotransporter-2 (SGLT2) inhibitors are a new class of oral
      antidiabetic drugs with an insulin-independent mechanism promoting urinary
      glucose excretion. We report the results of a combined Phase 2 and 3 clinical
      study (Japic CTI-101349) of the SGLT2 inhibitor tofogliflozin (CSG452, RG7201) in
      Japanese patients with type 2 diabetes mellitus. METHODS: The efficacy and safety
      of tofogliflozin were assessed in this multicenter, placebo-controlled,
      randomized, double-blind parallel-group study involving 230 patients with type 2
      diabetes mellitus with inadequate glycemic control on diet/exercise therapy.
      Between 30 October 2010 and 28 February 2012, patients at 33 centers were
      randomized to either placebo (n = 56) or tofogliflozin (10, 20, or 40 mg; n = 58
      each) orally, once daily for 24 weeks. The primary efficacy endpoint was the
      change from baseline in HbA1c at week 24. RESULTS: Overall, 229 patients were
      included in the full analysis set (placebo: n = 56; tofogliflozin 10 mg: n = 57;
      tofogliflozin 20 and 40 mg: n = 58 each). The least squares (LS) mean change (95%
      confidence interval) from baseline in HbA1c at week 24 was -0.028% (-0.192 to
      0.137) in the placebo group, compared with -0.797% (-0.960 to -0.634) in the
      tofogliflozin 10 mg group, -1.017% (-1.178 to -0.856) in the tofogliflozin 20 mg
      group, and -0.870% (-1.031 to -0.709) in the tofogliflozin 40 mg group (p <
      0.0001 for the LS mean differences in all tofogliflozin groups vs placebo). There
      were also prominent decreases in fasting blood glucose, 2-h postprandial glucose,
      and body weight in all tofogliflozin groups compared with the placebo group. The
      main adverse events were hyperketonemia, ketonuria, and pollakiuria. The
      incidence of hypoglycemia was low. Furthermore, most adverse events were
      classified as mild or moderate in severity. CONCLUSIONS: Tofogliflozin 10, 20, or
      40 mg administered once daily as monotherapy significantly decreased HbA1c and
      body weight, and was generally well tolerated in Japanese patients with type 2
      diabetes mellitus. Phase 3 studies were recently completed and support the
      findings of this combined Phase 2 and 3 study. TRIAL REGISTRATION: This study was
      registered in the JAPIC clinical trials registry (ID: Japic CTI-101349).

PMID- 24678907
TI  - Surface behavior of sphingomyelins with very long chain polyunsaturated fatty
      acids and effects of their conversion to ceramides.
AB  - Molecular species of sphingomyelin (SM) with nonhydroxy (n) and 2-hydroxy (h)
      very long chain polyunsaturated fatty acids (n- and h-28:4, 30:5, and 32:5)
      abound in rat spermatogenic cells and spermatozoa. These SMs are located on the
      sperm head, where they are converted to the corresponding ceramides (Cer) after
      the completion of the acrosomal reaction, as induced in vitro. The aim of this
      study was to look into the surface properties of these unique SM species and how
      these properties change by the SM -> Cer conversion. After isolation by HPLC,
      these SMs were organized in Langmuir films and studied alone, in combination with
      different proportions of Cer, and during their conversion to Cer by
      sphingomyelinase. Compression isotherms for all six SMs under study were
      compatible with a liquid-expanded (LE) state and showed large molecular areas.
      Only the longest SMs (n-32:5 and h-32:5 SM) underwent a phase transition upon
      cooling. Interestingly, the abundant h-28:4 Cer exhibited a highly compressible
      liquid-condensed (LC) phase compatible with a high conformational freedom of Cer
      molecules but with the characteristic low diffusional properties of the LC phase.
      In mixed films of h-28:4 SM/h-28:4 Cer, the components showed favorable mixing in
      the LE phase. The monolayer exhibited h-28:4 Cer-rich domains both in premixed
      films and when formed by the action of sphingomyelinase on pure h-28:4 SM films.
      Whereas the SMs from sperm behaved in a way similar to that of shorter acylated
      SMs, the corresponding Cers showed atypical rheological properties that may be
      relevant to the membrane structural rearrangements that take place on the sperm
      head after the completion of the acrosomal reaction. 

PMID- 24678909
TI  - Cross-validation pitfalls when selecting and assessing regression and
      classification models.
AB  - BACKGROUND: We address the problem of selecting and assessing classification and
      regression models using cross-validation. Current state-of-the-art methods can
      yield models with high variance, rendering them unsuitable for a number of
      practical applications including QSAR. In this paper we describe and evaluate
      best practices which improve reliability and increase confidence in selected
      models. A key operational component of the proposed methods is cloud computing
      which enables routine use of previously infeasible approaches. METHODS: We
      describe in detail an algorithm for repeated grid-search V-fold cross-validation
      for parameter tuning in classification and regression, and we define a repeated
      nested cross-validation algorithm for model assessment. As regards variable
      selection and parameter tuning we define two algorithms (repeated grid-search
      cross-validation and double cross-validation), and provide arguments for using
      the repeated grid-search in the general case. RESULTS: We show results of our
      algorithms on seven QSAR datasets. The variation of the prediction performance,
      which is the result of choosing different splits of the dataset in V-fold cross
      validation, needs to be taken into account when selecting and assessing
      classification and regression models. CONCLUSIONS: We demonstrate the importance
      of repeating cross-validation when selecting an optimal model, as well as the
      importance of repeating nested cross-validation when assessing a prediction
      error.

PMID- 24678910
TI  - Pathways of CH3Hg and Hg ingestion in benthic organisms: an enriched isotope
      approach.
AB  - Mercury is a widespread contaminant in marine food webs, and identifying uptake
      pathways of mercury species, CH3Hg(+) and Hg(2+), into low trophic level
      organisms is important to understanding its entry into marine food webs. Enriched
      stable isotope tracers were used to study benthic vs. pelagic pathways of
      CH3Hg(+) and Hg(2+) uptake via food to the infaunal estuarine amphipod,
      Leptocheirus plumulosus. Algal cells differentially labeled with isotopically
      enriched CH3Hg(+) or Hg(2+) were added simultaneously to the sediment and water
      column of microcosms, and Hg species were monitored in amphipods and in sediment
      and water compartments. Methylation of Hg(2+) occurred during the course of the
      experiment, enhancing the uptake of Hg(2+) spikes. Trophic transfer of Hg from
      algae added to the water column was determined to be the major uptake route for
      amphipods, suggesting inputs of contaminated organic matter from the pelagic zone
      are important to mercury bioaccumulation even in organisms living in sediments. 

PMID- 24678908
TI  - MicroRNAs in hematopoietic development.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short non-coding RNAs involved in the
      posttranscriptional regulation of a wide range of biological processes. By
      binding to complementary sequences on target messenger RNAs, they trigger
      translational repression and degradation of the target, eventually resulting in
      reduced protein output. MiRNA-dependent regulation of protein translation is a
      very widespread and evolutionarily conserved mechanism of posttranscriptional
      control of gene expression. Accordingly, a high proportion of mammalian genes are
      likely to be regulated by miRNAs. In the hematopoietic system, both
      transcriptional and posttranscriptional regulation of gene expression ensure
      proper differentiation and function of stem cells, committed progenitors as well
      as mature cells. RESULTS: In recent years, miRNA expression profiling of various
      cell types in the hematopoietic system, as well as gene-targeting approaches to
      assess the function of individual miRNAs, revealed the importance of this type of
      regulation in the development of both innate and acquired immunity. CONCLUSIONS:
      We discuss the general role of miRNA biogenesis in the development of
      hematopoietic cells, as well as specific functions of individual miRNAs in stem
      cells as well as in mature immune cells.

PMID- 24678911
TI  - The effectiveness of the quality program Pac-IficO to improve pain management in
      hospitalized cancer patients: a before-after cluster phase II trial.
AB  - BACKGROUND: Cancer-related pain continues to be a major healthcare issue
      worldwide. Despite the availability of effective analgesic drugs, published
      guidelines and educational programs for Health Care Professionals (HCPs) the
      symptom is still under-diagnosed and its treatment is not appropriate in many
      patients. The objective of the study is to evaluate the efficacy of the Pac-IFicO
      programme in improving the quality of pain management in hospitalised cancer
      patients. METHODS/DESIGN: This is a before-after cluster phase II study. After
      the before assessment, the experimental intervention - the Pac-IFicO programme -
      will be implemented in ten medicine, oncology and respiratory disease hospital
      wards. The same assessment will be repeated after the completion of the
      intervention. The Pac-IFicO programme is a complex intervention with multiple
      components. It includes focus group with ward professionals for identifying
      possible local obstacles to optimal pain control, informative material for the
      patients, an educational program performed through guides from the wards, and an
      organisational intervention to the ward. The primary end-point of the study is
      the proportion of cancer patients with severe pain. Secondary end-points include
      opioids administered in the wards, knowledge in pain management, and quality of
      pain management. We plan to recruit about 500 cancer patients. This sample size
      should be sufficient, after appropriate statistical adjustments for clustering,
      to detect an absolute decrease in the primary end-point from 20% to 9%.
      DISCUSSION: This trial is aimed at exploring with an experimental approach the
      efficacy of a new quality improvement educational intervention. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02035098.

PMID- 24678912
TI  - Cardiorenal protection in experimental hypertension with renal failure:
      comparison between vasopeptidase inhibition and angiotensin receptor blockade.
AB  - OBJECTIVE: The aim of the present study was to compare the preventive impact of
      treatment with a vasopeptidase inhibitor (VPI) with an angiotensin-receptor
      blocker (ARB) on left ventricular (LV) function and renal damage in rats with
      renal failure after 5/6 renal ablation (Nx). METHODS: Rats (n = 15-20, each
      group) underwent either sham-operation (Sham) or 5/6 renal ablation (Nx). Two
      additional groups of Nx-animals (groups Nx-VPI and Nx-ARB) were treated with the
      VPI ilepatril (AVE7688, 30 mg kg(-1) d(-1)) or with the ARB olmesartan (10 mg kg(
      1 )d(-1)). Animals were followed for 4 weeks. RESULTS: Systolic blood pressure
      (SBP), LV hypertrophy (LVH) and LV end-diastolic pressure (LVEDP) were increased
      4 weeks after Nx (p < 0.05). LV pressure rise (+dP/dt/LVPmax), LV pressure fall (
      dP/dt/LVPmax), and creatinine clearance decreased, while albuminuria and renal
      glomerulosclerosis index (GSI) increased with Nx (p < 0.05, respectively). In
      comparison to Nx, treatment with both VPI and ARB normalized SBP, LVH, LVEDP,
      +dP/dt/LVPmax, and -dP/dt/LVPmax to Sham control levels. GSI, but not creatinine
      clearance, was also normalized in response to both treatments. The significant
      increase in albuminuria observed in Nx (+230-fold versus Sham, p < 0.0001) was
      partially reduced in Nx-VPI (+47-fold versus Sham, p < 0.0001) and fully
      abolished in Nx-ARB. CONCLUSIONS: Both ilepatril and olmesartan conferred strong
      cardiorenal protective effects in rats with renal failure. While cardioprotection
      was clearly comparable with both treatment regimens, the ARB provided a better
      protection against the increase in albuminuria, although renal function and
      structural kidney changes were similarly affected by the VIP and ARB.

PMID- 24678913
TI  - Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene
      polymorphism and type 2 diabetic nephropathy risk: a meta-analysis.
AB  - Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene
      polymorphism and type 2 diabetic nephropathy (T2DN) risk is still unclear. This
      study was performed to evaluate if there is an association between the MTHFR
      A1298C gene polymorphism and T2DN risk using meta-analysis. The relevant reports
      were searched and identified from PubMed, Cochrane Library on 1 October 2013, and
      eligible studies were included and synthesized. Eight reports were recruited into
      this meta-analysis for the association of the MTHFR A1298C gene polymorphism with
      T2DN risk. The MTHFR A1298C C allele or CC genotype was shown to be not
      associated with T2DN risk (C allele: OR = 0.76, 95% CI: 0.43-1.34, p = 0.34; CC
      genotype: OR = 1.18, 95% CI: 0.63-2.22, p = 0.60). Interestingly, AA genotype was
      associated with the T2DN risk (OR = 0.68, 95% CI: 0.49-0.96, p = 0.03). In the
      sensitivity analysis according to the Hardy-Weinberg equilibrium (HWE), the
      results were consistent with those in non-sensitivity analysis. However, in the
      sensitivity analysis according to the control source from hospital, sample size
      of case (>= 100), sample size of case (<100), the MTHFR A1298C gene polymorphism
      was not associated with T2DN risk. In conclusion, the MTHFR A1298C gene
      polymorphism was not associated with T2DN risk. However, additional studies are
      required to firmly establish a correlation between the MTHFR A1298C gene
      polymorphism and T2DN risk.

PMID- 24678914
TI  - Is symmetric dimethylarginine a sensitive biomarker of subclinical kidney injury
      in children born with low birth weight?
AB  - OBJECTIVE: The aim of this study was to investigate if Symmetric Dimethylarginine
      (SDMA) is a sensitive biomarker of renal function and may predict subclinical
      kidney injury in low birth weight (LBW) children. METHODS: We studied 68 LBW
      children and 20 children as reference group. An enzyme-linked immunosorbent assay
      was used to measure serum SDMA and Cystatin C (Cys C). RESULTS: SDMA levels were
      higher in study groups compared to reference groups. There was a strong
      correlation between SDMA and Cys C, also SDMA negatively correlated with eGFR.
      CONCLUSION: Elevated SDMA concentration may play an important role in
      pathogenesis of chronic kidney disease.

PMID- 24678915
TI  - Acute nutrient regulation of the mitochondrial glutathione redox state in
      pancreatic beta-cells.
AB  - The glucose stimulation of insulin secretion by pancreatic beta-cells depends on
      increased production of metabolic coupling factors, among which changes in NADPH
      and ROS (reactive oxygen species) may alter the glutathione redox state (EGSH)
      and signal through changes in thiol oxidation. However, whether nutrients affect
      EGSH in beta-cell subcellular compartments is unknown. Using redox-sensitive GFP2
      fused to glutaredoxin 1 and its mitochondria-targeted form, we studied the acute
      nutrient regulation of EGSH in the cytosol/nucleus or the mitochondrial matrix of
      rat islet cells. These probes were mainly expressed in beta-cells and reacted to
      low concentrations of exogenous H2O2 and menadione. Under control conditions,
      cytosolic/nuclear EGSH was close to -300 mV and unaffected by glucose (from 0 to
      30 mM). In comparison, mitochondrial EGSH was less negative and rapidly regulated
      by glucose and other nutrients, ranging from -280 mV in the absence of glucose to
      -299 mV in 30 mM glucose. These changes were largely independent from changes in
      intracellular Ca(2+) concentration and in mitochondrial pH. They were unaffected
      by overexpression of SOD2 (superoxide dismutase 2) and mitochondria-targeted
      catalase, but were inversely correlated with changes in NAD(P)H autofluorescence,
      suggesting that they indirectly resulted from increased NADPH availability rather
      than from changes in ROS concentration. Interestingly, the opposite regulation of
      mitochondrial EGSH and NAD(P)H autofluorescence by glucose was also observed in
      human islets isolated from two donors. In conclusion, the present study
      demonstrates that glucose and other nutrients acutely reduce mitochondrial, but
      not cytosolic/nuclear, EGSH in pancreatic beta-cells under control conditions.

PMID- 24678916
TI  - Healthy ageing from the perspective of older people: a capability approach to
      resilience.
AB  - A policy focus on healthy ageing has been critiqued for homogenising, oppressing
      and neglecting the physical realities of older age. Current healthy ageing
      discourse places responsibility on individuals for achieving good physical health
      and ignores their broader circumstances. Sen's capability approach provides a
      basis for including the physical changes of ageing and the social environment by
      focusing on what older people themselves value in regards to healthy ageing.
      Accounts of desired living standards in 145 interviews with people aged 63-93
      years in New Zealand were subjected to a thematic analysis which revealed six
      commonly valued 'functionings': physical comfort, social integration,
      contribution, security, autonomy and enjoyment. The capability to achieve the
      valued functionings was of high importance regardless of physical health status
      while this capability was often limited by social and material circumstances. The
      importance of an environment supportive of valued functionings provides a
      framework for understanding health for older adults, whatever their present
      physical abilities. We suggest that health psychology is in a good position to
      reflect critically on the impact of discourses promoting healthy ageing in the
      lives of older adults, and consider broader models that include understandings of
      resilience and capability.

PMID- 24678917
TI  - Cardiovascular guidelines: separate career may help attenuate controversy.
AB  - The release of recent guidelines for high cholesterol, hypertension and diabetes
      in the U.S. has been accompanied by great noise and concerns, both in the
      academic circuits and the lay press. For persons aged 40 to 75 years, with LDL
      cholesterol levels between 70-189 mg/dL and 7.5% or higher estimated 10-year
      risk, the peril of a global "statinization" has been advocated, predicting a 70%
      increase of statin use in this otherwise healthy people. A minority of the Eight
      Joint National Committee panel disagreed with the recommendation to increase the
      target systolic blood pressure from 140 to 150 mmHg in persons aged 60 years or
      older without diabetes mellitus or chronic kidney disease. The 2013-American
      Association of Clinical Endocrinologists algorithm and consensus statement on
      diabetes has been criticized with particular concerns about transparency,
      conflicts of interest, group composition, and the abundant use of personal
      judgment and experience instead of rigorous methodology. Separate careers for
      experts who collect evidence from persons who write the actual guidelines seems a
      good opportunity in order to attenuate the noise associated with release of new
      guidelines, especially those that counter prior practice.

PMID- 24678918
TI  - Exploring recruitment barriers and facilitators in early cancer detection trials:
      the use of pre-trial focus groups.
AB  - BACKGROUND: Recruiting to randomized controlled trials is fraught with
      challenges; with less than one third recruiting to their original target. In
      preparation for a trial evaluating the effectiveness of a blood test to screen
      for lung cancer (the ECLS trial), we conducted a qualitative study to explore the
      potential barriers and facilitators that would impact recruitment. METHODS:
      Thirty two people recruited from community settings took part in four focus
      groups in Glasgow and Dundee (UK). Thematic analysis was used to code the data
      and develop themes. RESULTS: Three sub-themes were developed under the larger
      theme of recruitment strategies. The first of these themes, recruitment options,
      considered that participants largely felt that the invitation to participate
      letter should come from GPs, with postal reminders and face-to-face reminders
      during primary care contacts. The second theme dealt with understanding
      randomization and issues related to the control group (where bloods were taken
      but not tested). Some participants struggled with the concept or need for
      randomization, or for the need for a control group. Some reported that they would
      not consider taking part if allocated to the control group, but others were
      motivated to take part even if allocated to the control group by altruism. The
      final theme considered perceived barriers to participation and included practical
      barriers (such as flexible appointments and reimbursement of travel expenses) and
      psychosocial barriers (such as feeling stigmatized because of their smoking
      status and worries about being coerced into stopping smoking). CONCLUSIONS: Focus
      groups provided useful information which resulted in numerous changes to proposed
      trial documentation and processes. This was in order to address participants
      information needs, improve comprehension of the trial documentation, enhance
      facilitators and remove barriers to participation. The modifications made in
      light of these findings may enhance trial recruitment and future trials may wish
      to consider use of pretrial focus groups.

PMID- 24678919
TI  - Reassessing the link between herpes zoster ophthalmicus and stroke.
AB  - This editorial will assess a proposed link between herpes zoster ophthalmicus and
      subsequent stoke. Herpes zoster (also called shingles) is caused by varicella
      zoster virus (VZV), one of the 9 human herpesviruses. When children contract
      their primary VZV infection, virus often travels to the trigeminal ganglia and
      establishes latency. Upon reactivation in late adulthood, the same virus travels
      anterograde to cause herpes zoster ophthalmicus. In some people, the virus also
      traffics from the same trigeminal ganglion along afferent fibers around the
      carotid artery and its branches. Subsequently VZV-induced inflammation within the
      affected cerebral arteries leads to occlusion and stroke. In one retrospective
      analysis of people with herpes zoster ophthalmicus, there was a 4.5 fold higher
      risk of stroke than in a control group. Two other studies found a less compelling
      association. 

PMID- 24678920
TI  - Risk factors of hepatitis B transmission in northern Palestine: a case - control
      study.
AB  - BACKGROUND: The Hepatitis B (HB) infection is a significant health problem in
      Palestine, which is categorized as an HB virus moderate endemic area, with the HB
      carrier rate ranging from 2-6%. The aim of this study is to determine the risk
      factors of Hepatitis transmission in the northern areas of Palestine in order to
      help prevent and control this prevalent health problem. METHODS: A case-control
      study was implemented to achieve the study objectives. One hundred HB virus
      seropositive cases and another 100 seronegative controls were included in the
      study. Univariate analysis and a logistic regression model were performed to
      examine probable risk factors of acquisition of HB infections. RESULTS:
      Univariate analysis showed that HB case-patients were more likely to report
      having a history of blood transfusion, dental visits, hospitalization, Hejamat,
      sharing shaving equipments, intravenous drug use, or living abroad than controls
      were. The logistic regression model revealed a history of dental visits to be the
      most significant risk factor, (P value <0.001, OR 5.6; 95% CI 2.8-11.1).
      CONCLUSION: The presence of these risk factors emphasizes the need for both
      increasing the uptake of HB vaccine and implementing risk-targeted public health
      education. Development and enforcement of appropriate infection control
      guidelines for dental care services are important to prevent HB virus
      transmission as well.

PMID- 24678921
TI  - Cell adhesion in the assembly of the Drosophila eye.
AB  - Differential adhesion provides a mechanical force to drive cells into stable
      configurations during the assembly of tissues and organs. This is well
      illustrated in the Drosophila eye where differential adhesion plays a role in
      sequential recruitment of all support cells. Cell adhesion, on the other hand, is
      linked to the cytoskeleton and subject to regulation by cell signaling. The
      integration of cell adhesion with the cytoskeleton and cell signaling may provide
      a more thorough explanation for the diversity of forms and shapes seen in tissues
      and organs.

PMID- 24678922
TI  - Discovery and mechanistic studies of facile N-terminal Calpha-C bond cleavages in
      the dissociation of tyrosine-containing peptide radical cations.
AB  - Fascinating N-terminal Calpha-C bond cleavages in a series of nonbasic tyrosine
      containing peptide radical cations have been observed under low-energy collision
      induced dissociation (CID), leading to the generation of rarely observed x-type
      radical fragments, with significant abundances. CID experiments of the radical
      cations of the alanyltyrosylglycine tripeptide and its analogues suggested that
      the N-terminal Calpha-C bond cleavage, yielding its [x2 + H](*+) radical cation,
      does not involve an N-terminal alpha-carbon-centered radical. Theoretical
      examination of a prototypical radical cation of the alanyltyrosine dipeptide,
      using density functional theory calculations, suggested that direct N-terminal
      Calpha-C bond cleavage could produce an ion-molecule complex formed between the
      incipient a1(+) and x1(*) fragments. Subsequent proton transfer from the iminium
      nitrogen atom in a1(+) to the acyl carbon atom in x1(*) results in the observable
      [x1 + H](*+). The barriers against this novel Calpha-C bond cleavage and the
      competitive N-Calpha bond cleavage, forming the complementary [c1 + 2H](+)/[z1 -
      H](*+) ion pair, are similar (ca. 16 kcal mol(-1)). Rice-Ramsperger-Kassel-Marcus
      modeling revealed that [x1 + H](*+) and [c1 + 2H](+) species are formed with
      comparable rates, in agreement with energy-resolved CID experiments for [AY](*+).

PMID- 24678923
TI  - Loss of K+ currents in heart failure is accentuated in KChIP2 deficient mice.
AB  - INTRODUCTION: KV 4 together with KV Channel-Interacting Protein 2 (KChIP2)
      mediate the fast recovering transient outward potassium current (I(to,f)) in the
      heart. KChIP2 is downregulated in human heart failure (HF), potentially
      underlying the loss of I(to,f). We investigated remodeling associated with HF
      hypothesizing that KChIP2 plays a central role in the modulation of outward K(+)
      currents in HF. METHODS AND RESULTS: HF was induced by aortic banding in wild
      type (WT) and KChIP2 deficient (KChIP2(-/-)) mice, evaluated by echocardiography.
      Action potentials were measured by floating microelectrodes in intact hearts.
      Ventricular cardiomyocytes were isolated and whole-cell currents were recorded by
      patch clamp. Left ventricular action potentials in KChIP2(-/-) mice were
      prolonged in a rate dependent manner, consistent with patch-clamp data showing
      loss of a fast recovering outward K(+) current and upregulation of the slow
      recovering I(to,s) and I(Kur). HF decreased all outward K(+) currents in WT mice
      and did not change the relative contribution of I(to,f) in WT mice. Compared to
      WT HF, KChIP2(-/-) HF had a larger reduction of K(+) -current density. However,
      the relative APD prolongation caused by HF was shorter for KChIP2(-/-) compared
      with WT, and the APs of the 2 HF mouse types were indistinguishable. CONCLUSION:
      I(to,f) is just one of many K(+) currents being downregulated in murine HF. The
      downregulation of repolarizing currents in HF is accentuated in KChIP2(-/-) mice.
      However, the prolongation of APs associated with HF is less in KChIP2(-/-)
      compared to WT, suggesting other compensatory mechanism(s) in the KChIP2(-/-)
      mouse.

PMID- 24678924
TI  - Hydration of atmospherically relevant molecular clusters: computational chemistry
      and classical thermodynamics.
AB  - Formation of new particles through clustering of molecules from condensable
      vapors is a significant source for atmospheric aerosols. The smallest clusters
      formed in the very first steps of the condensation process are, however, not
      directly observable by experimental means. We present here a comprehensive series
      of electronic structure calculations on the hydrates of clusters formed by up to
      four molecules of sulfuric acid, and up to two molecules of ammonia or
      dimethylamine. Though clusters containing ammonia, and certainly dimethylamine,
      generally exhibit lower average hydration than the pure acid clusters,
      populations of individual hydrates vary widely. Furthermore, we explore the
      predictions obtained using a thermodynamic model for the description of these
      hydrates. The similar magnitude and trends of hydrate formation predicted by both
      methods illustrate the potential of combining them to obtain more comprehensive
      models. The stabilization of some clusters relative to others due to their
      hydration is highly likely to have significant effects on the overall processes
      that lead to formation of new particles in the atmosphere. 

PMID- 24678925
TI  - Adjusted color probability codes for peripapillary retinal nerve fiber layer
      thickness in healthy Koreans.
AB  - BACKGROUND: Though a newly developed spectral domain optical coherence tomography
      (OCT) is at the center of interests for many ophthalmologic researchers and
      clinicians, its own characteristics are not fully evaluated yet. The main purpose
      of this study was to establish the adjusted color probability codes for
      peripapillary retinal nerve fiber layer (RNFL) thickness in healthy Koreans and
      to compare them with original color codes provided by spectral domain OCT.
      METHODS: Two hundred ninety-five healthy Korean eyes were enrolled and their
      peripapillary RNFL thickness was measured by Cirrus OCT. For each decade of age,
      the normal thickness reference was determined on the basis of z-scores and the
      adjusted color probability codes were established. Then the agreements between
      adjusted and original color codes were calculated using weighted Kappa (Kw)
      coefficient. RESULTS: On the basis of Kw coefficient, the overall agreement
      between the adjusted and original probability color codes was not excellent (Kw
      range of 0.500 to 0.806). If the adjusted probability codes were assumed as a
      standard of comparison, the original color codes showed the false-negative in 11%
      of eyes and the false-positive in 0.3% of eyes for average RNFL thickness.
      CONCLUSIONS: Adjusted color probability codes judged by the Korean normative data
      showed a discrepancy with original codes. It implies that normal reference and
      adjusted probability codes for each ethnicity might be needed to determine
      whether a certain RNFL thickness is within normal range or not.

PMID- 24678926
TI  - Dissociative amnesia in dissociative disorders and borderline personality
      disorder: self-rating assessment in a college population.
AB  - Dissociative amnesia (DA) among subjects with a dissociative disorder and/or
      borderline personality disorder (BPD) recruited from a nonclinical population was
      examined. The Steinberg Dissociative Amnesia Questionnaire (SDAQ), the Childhood
      Trauma Questionnaire, and the self-report screening tool of the BPD section of
      the Structured Clinical Interview for DSM-IV(SCID-BPD) were administered to 1,301
      college students. A total of 80 participants who were diagnosed with BPD
      according to the clinician-administered SCID-BPD and 111 nonborderline controls
      were evaluated using the Structured Clinical Interview for DSM-IV Dissociative
      Disorders (SCID-D) by a psychiatrist blind to diagnosis and scale scores.
      Internal consistency analyses and test-retest evaluations suggested that the SDAQ
      is a reliable instrument for the population studied. Of the participants, 20.6%
      reported an SDAQ score of 20 or above and impairment by DA. Those who had both
      dissociative disorder and BPD (n = 78) had the highest SDAQ scores. Both
      disorders had significant effects on the SCID-D total and amnesia scores in the
      variance analysis. On SDAQ scores, however, only BPD had this effect. There was a
      significant interaction between the 2 disorders for the SCID-D total but not for
      the SDAQ or SCID-D amnesia scores. BPD represented the severity of dissociation
      and childhood trauma in this study group. However, in contrast to the
      dissociative disorders, BPD was characterized by better awareness of DA in self
      report. The discrepancies between self-report and clinical interview associated
      with BPD and dissociative disorders are discussed in the context of betrayal
      theory (J. J. Freyd, 1994) of BPD and perceptual theory (D. B. Beere, 2009) of
      dissociative disorders. 

PMID- 24678927
TI  - A facile methodology for the production of in situ inorganic nanowire
      hydrogels/aerogels.
AB  - Creating inorganic nanowire hydrogels/aerogels using various materials and
      inexpensive means remains an outstanding challenge despite their importance for
      many applications. Here, we present a facile methodology to enable highly porous
      inorganic nanowire hydrogel/aerogel production on a large scale and at low cost.
      The hydrogels/aerogels are obtained from in situ hydrothermal synthesis of one
      dimensional (1D) nanowires that directly form a cross-linking network during the
      synthesis process. Such a method not only offers great simplicity but also allows
      the interconnecting nanowires to have much longer length. The longer length
      offers aerogels with remarkable porosity and surface area extremely low densities
      (as low as 2.9 mg/cm(3)), are mechanically robust, and can have superelasticity
      by tuning the synthesis conditions. The nanowires in the hydrogels/aerogels serve
      both as structural support and active sites, for example, for catalysis or
      absorption. In this work, we have found that the as-grown hydrogels can be used
      directly as water filters to remove pollutants such as heavy metal ions and toxic
      organic contents. Our studies indicate that this method for nanowire
      hydrogels/aerogels production is not only economical but greatly augmented their
      applications in environmental, catalysis, sensing, absorption, energy storage,
      and beyond. 

PMID- 24678928
TI  - Association of classical risk factors and coronary artery disease in type 2
      diabetic patients submitted to coronary angiography.
AB  - BACKGROUND: Coronary artery disease (CAD) is the leading cause of death among
      individuals with type 2 diabetes (T2DM). T2DM accelerates atherosclerosis
      alongside classical risk factors such as dyslipidemia and hypertension. This
      study aims to investigate the association of hyperglycemia and associated risk
      factors with CAD in outpatients with T2DM undergoing coronary angiography.
      METHODS: 818 individuals referred to coronary angiography were evaluated for
      glucose disturbances. After exclusion of those with prediabetes, 347 individuals
      with T2DM and 94 normoglycemic controls were studied for BMI, blood pressure,
      fasting plasma glucose, HbA1c, lipids, HOMA, adiponectin, Framingham risk score,
      number of clinically significant coronary lesions (stenosis > 50%). RESULTS:
      Among T2DM subjects, those with CAD (n = 237) had worse glycemic control (fasting
      glucose 162.3 + 69.8 vs. 143.4 + 48.9 mg/dL, p = 0.004; HbA1c 8.03 + 1.91 vs.
      7.59 + 1.55%, p = 0.03), lower HDL (39.2 + 13.2 vs. 44.4 + 15.9 mg/dL, p =
      0.003), and higher triglycerides (140 [106-204] vs. 121 [78.5-184.25] mg/dL, p =
      0.002), reached more often therapeutic goals for LDL (63.4% vs. 51.4%, p = 0.037)
      and less often goals for HDL (26.6% vs. 37.3%, p = 0.04), when compared to CAD
      free individuals (n = 110). The same differences were not seen in normoglycemic
      controls. In T2DM subjects HbA1c tertiles were associated with progressively
      higher number of significant coronary lesions (median number of lesions 2 [A1c <
      6.8%]; 2.5 [A1c 6.8-8.2%]; 4 [A1c > 8.2%]; p = 0.01 for trend). CONCLUSIONS:
      Classic risk factors such as glycemic control and lipid profile were associated
      with presence of CAD in T2DM subjects undergoing coronary angiography. Glycemic
      control is progressively associated with number and extent of coronary lesions in
      patients with T2DM.

PMID- 24678930
TI  - Automatic control of negative emotions: evidence that structured practice
      increases the efficiency of emotion regulation.
AB  - Emotion regulation (ER) is vital to everyday functioning. However, the effortful
      nature of many forms of ER may lead to regulation being inefficient and
      potentially ineffective. The present research examined whether structured
      practice could increase the efficiency of ER. During three training sessions,
      comprising a total of 150 training trials, participants were presented with
      negatively valenced images and asked either to "attend" (control condition) or
      "reappraise" (ER condition). A further group of participants did not participate
      in training but only completed follow-up measures. Practice increased the
      efficiency of ER as indexed by decreased time required to regulate emotions and
      increased heart rate variability (HRV). Furthermore, participants in the ER
      condition spontaneously regulated their negative emotions two weeks later and
      reported being more habitual in their use of ER. These findings indicate that
      structured practice can facilitate the automatic control of negative emotions and
      that these effects persist beyond training. 

PMID- 24678929
TI  - Identification and functional characterization of a flax UDP-glycosyltransferase
      glucosylating secoisolariciresinol (SECO) into secoisolariciresinol monoglucoside
      (SMG) and diglucoside (SDG).
AB  - BACKGROUND: Lignans are a class of diphenolic nonsteroidal phytoestrogens often
      found glycosylated in planta. Flax seeds are a rich source of
      secoisolariciresinol diglucoside (SDG) lignans. Glycosylation is a process by
      which a glycosyl group is covalently attached to an aglycone substrate and is
      catalyzed by uridine diphosphate glycosyltransferases (UGTs). Until now, very
      little information was available on UGT genes that may play a role in flax SDG
      biosynthesis. Here we report on the identification, structural and functional
      characterization of 5 putative UGTs potentially involved in secoisolariciresinol
      (SECO) glucosylation in flax. RESULTS: Five UGT genes belonging to the
      glycosyltransferases' family 1 (EC 2.4.x.y) were cloned and characterized. They
      fall under four UGT families corresponding to five sub-families referred to as
      UGT74S1, UGT74T1, UGT89B3, UGT94H1, UGT712B1 that all display the characteristic
      plant secondary product glycosyltransferase (PSPG) conserved motif. However,
      diversity was observed within this 44 amino acid sequence, especially in the two
      peptide sequences WAPQV and HCGWNS known to play a key role in the recognition
      and binding of diverse aglycone substrates and in the sugar donor specificity. In
      developing flax seeds, UGT74S1 and UGT94H1 showed a coordinated gene expression
      with that of pinoresinol-lariciresinol reductase (PLR) and their gene expression
      patterns correlated with SDG biosynthesis. Enzyme assays of the five
      heterologously expressed UGTs identified UGT74S1 as the only one using SECO as
      substrate, forming SECO monoglucoside (SMG) and then SDG in a sequential manner.
      CONCLUSION: We have cloned and characterized five flax UGTs and provided evidence
      that UGT74S1 uses SECO as substrate to form SDG in vitro. This study allowed us
      to propose a model for the missing step in SDG lignan biosynthesis.

PMID- 24678931
TI  - Using EFA and FIM rating scales could provide a more complete assessment of
      patients with acquired brain injury.
AB  - PURPOSE: In some hospitals, patients exhibit significant heterogeneity of
      function at admission and discharge. The current study aims to assess if
      concurrent usage of the Early Functional Assessment (EFA) and Functional
      Independence Measure (FIM) is warranted and practical in rehabilitation centers
      with diverse patient groups and outcomes. METHODS: This retrospective study
      examined a data set of all patients with concurrent EFA and FIM scores admitted
      to a single rehabilitation center (4076 scores from 1251 patients). The patients
      had acquired brain injury of multiple etiologies and a range of severities.
      RESULTS: The EFA scale was more able to characterize the function of lower
      functioning patients according to the FIM while the FIM scale was more able to
      characterize the function of higher functioning patients according to the EFA.
      This was highlighted by 21% of assessments with the lowest FIM score (18) having
      corresponding EFA scores of 22-76 and 27% of assessments with the highest EFA
      score (>90) having corresponding FIM scores of 38-126. CONCLUSIONS: In
      rehabilitation centers with diverse patient groups and outcomes, the FIM and EFA
      scale could be used to characterize the heterogeneity of function in patients
      with acquired brain injury. The EFA/FIM scale could be used concurrently in
      certain patients providing a more complete view of patients throughout the
      rehabilitation process.

PMID- 24678932
TI  - "Fastening" porphyrin in highly cross-linked polyphosphazene hybrid
      nanoparticles: powerful red fluorescent probe for detecting mercury ion.
AB  - It is a significant issue to overcome the concentration-quenching effect of the
      small fluorescent probes and maintain the high fluorescent efficiency at high
      concentration for sensitive and selective fluorescent mark or detection. We
      developed a new strategy to "isolate" and "fasten" porphyrin moieties in a highly
      cross-linked poly(tetraphenylporphyrin-co-cyclotriphosphazene) (TPP-PZS) by the
      polycondensation of hexachlorocyclotriphosphazene (HCCP) and 5,10,15,20
      tetrakis(4-hydroxyphenyl)porphyrin (TPP-(OH)4) in a suitable solvent. The
      resulting TPP-PZS particles were characterized with transmission electron
      microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared
      (FTIR), (31)P nuclear magnetic resonance (NMR), and ultraviolet and visible (UV
      vis) absorption spectra. Remarkably, TPP-PZS particles obtained in acetone
      emitted a bright red fluorescence both in powder state and in solution because
      the aggregation of porphyrin moieties in "H-type" (face-to-face) and "J-type"
      (edge-to-edge) was effectively blocked. The fluorescent TPP-PZS particles also
      showed superior resistance to photobleaching, and had a high sensitivity and
      selectivity for the detection of Hg(2+) ions. The TPP-PZS particles were
      therefore used as an ideal material for preparing test strips to quickly
      detect/monitor the Hg(2+) ions in a facile way. 

PMID- 24678933
TI  - Superior mediastinal paraganglioma associated with von Hippel-Lindau syndrome:
      report of a case.
AB  - Extra-adrenal pheochromocytomas are termed paragangliomas. Paragangliomas in the
      mediastinum, especially the superior mediastinum, are extremely rare. It is known
      that paragangliomas or pheochromocytomas occur in combination with von Hippel
      Lindau syndrome. We present the case of a non-functional superior mediastinal
      paraganglioma in a patient with von Hippel-Lindau syndrome, without a familial
      history suggestive of the condition. This case highlights that we should be aware
      of possible sporadic von Hippel-Lindau syndrome in patients with a mediastinal
      paraganglioma. 

PMID- 24678934
TI  - Adsorption of polycyclic aromatic hydrocarbons by graphene and graphene oxide
      nanosheets.
AB  - The adsorption of naphthalene, phenanthrene, and pyrene onto graphene (GNS) and
      graphene oxide (GO) nanosheets was investigated to probe the potential adsorptive
      sites and molecular mechanisms. The microstructure and morphology of GNS and GO
      were characterized by elemental analysis, XPS, FTIR, Raman, SEM, and TEM.
      Graphene displayed high affinity to the polycyclic aromatic hydrocarbons (PAHs),
      whereas GO adsorption was significantly reduced after oxygen-containing groups
      were attached to GNS surfaces. An unexpected peak was found in the curve of
      adsorption coefficients (Kd) with the PAH equilibrium concentrations. The
      hydrophobic properties and molecular sizes of the PAHs affected the adsorption of
      G and GO. The high affinities of the PAHs to GNS are dominated by pi-pi
      interactions to the flat surface and the sieving effect of the powerful groove
      regions formed by wrinkles on GNS surfaces. In contrast, the adsorptive sites of
      GO changed to the carboxyl groups attaching to the edges of GO because the groove
      regions disappeared and the polar nanosheet surfaces limited the pi-pi
      interactions. The TEM and SEM images initially revealed that after loading with
      PAH, the conformation and aggregation of GNS and GO nanosheets dramatically
      changed, which explained the observations that the potential adsorption sites of
      GNS and GO were unusually altered during the adsorption process. 

PMID- 24678935
TI  - The potential of microRNAs as biofluid markers of neurodegenerative diseases--a
      systematic review.
AB  - MicroRNAs (miRNA) are biological molecules transcribed from non-protein coding
      regions of the genome, participating in regulating cellular processes. MiRNAs in
      biofluids may possess neurodegenerative disease biomarker potential for screening
      tests, differential diagnosis and disease progression monitoring. This systematic
      review clarifies biomarker potential of miRNAs detected in biofluids of
      neurodegenerative disease patients. Thirty-three and ten miRNAs displayed
      significant expression between patients with multiple sclerosis and Alzheimer's
      disease, respectively, compared to healthy controls in minimum two studies.
      Thirty-eight miRNAs showed biomarker potential by distinguishing significantly
      between minimum two diseases. Summarized data directs future research towards
      discovering new biomarkers for neurodegenerative diseases.

PMID- 24678936
TI  - Two cases of multiple ossifying fibromas in the jaws.
AB  - BACKGROUND: The clinicopathologic characteristics of multiple ossifying fibroma
      (OF) are unclear due to the condition's rarity, making diagnosis challenging.
      Sporadic multiple OFs must be distinguished from hyperparathyroidism-jaw tumour
      syndrome (HPT-JT) related OF and other fibro-osseous lesions. METHODS: Multiple
      OF cases were identified from ossifying fibroma cases. Clinical data including
      age, sex, anatomic site, radiographic features, clinical impression, treatment
      and available follow-up data as well as serum calcium, phosphorus, and
      parathyroid hormone (PTH) were recorded. GNAS and HRPT2 genetic mutations were
      examined in the two present cases. Case reports of sporadic multiple ossifying
      fibroma and HPT-JT-related OF were also reviewed. RESULTS: The two present cases
      were confirmed as sporadic multiple OF, with no genetic GNAS and HRPT2 mutations
      found. The incidence of sporadic multiple ossifying fibroma was 2.0% (2/102). The
      total 18 sporadic multiform OF cases were characterized as followed: 13 (72.2%)
      female; 5 (27.8%) male; mean age 28.6 years; 2/16 (11.1%) cases only in the
      mandible; 4/18 (22.2%) cases only in the maxilla; and 12/18 (66.7%) cases in both
      the maxilla and mandible. Radiographically, the lesions were radiolucent in 5/18
      (27.8%) cases and mixed density in 13/18 (72.2%) cases. Along with 24 cases of
      HPT-JT related OF were reviewed, sixteen (66.7%) patients were diagnosed with a
      single lesion, and 8 patients (33.3%) were diagnosed with multiple jaw lesions.
      CONCLUSIONS: Sporadic multiple OFs are very rare, but must be distinguished from
      HPT-JT related OF. We strongly recommend that patients diagnosed with multiple
      ossifying fibromas receive serum PTH testing and mutation screening of HRPT2.
      VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/1194507146115753.

PMID- 24678938
TI  - Renal denervation for resistant hypertension?

PMID- 24678940
TI  - Liver X receptor: from metabolism to cancer.
AB  - Cholesterol plays an indispensable role in regulating the properties of cell
      membranes in mammalian cells. Accumulation of cholesterol and its intermediates,
      such as oxysterols, lead to activation of the nuclear receptors LXRs (liver X
      receptors). LXR is an important regulator of cholesterol homoeostasis by
      controlling its transport and its neo-synthesis. Accumulating evidence indicates
      that the endogenous ligands of LXRs, oxysterols, play an active and important
      role in regulating the fate and function of immune cells. Indeed, LXRs are
      negative regu-lators of innate immunity by interfering with macrophage
      activation. Recent advances have highlighted a controversial role for LXR in
      cancer. In this issue of the Biochemical Journal, Wang et al. propose that LXR
      agonist directly controls IFN-gamma (interferon-gamma) expression, which limits
      tumour growth. This protective effect mediated by LXR appears to be dependent on
      IFN-gamma. Thus, despite accumulation of endogenous ligand of LXR in cancer,
      activation of LXR seems protective. This novel evidence provides a new
      perspective for targeting LXR in cancer, although controversial studies can be
      also found in the literature. In order to avoid side effects associated with LXR
      agonists, molecular and cellular studies are required to decipher this unexpected
      action of LXRs. 

PMID- 24678941
TI  - Burden for family carers at the end of life; a mixed-method study of the
      perspectives of family carers and GPs.
AB  - BACKGROUND: Since many patients spend most of the time at home at the end of
      life, this may affect the burden for family carers and constitute a risk factor
      for the patients' hospitalisation. This study aimed to explore family carers'
      burden in the final three months of the patient's life, from the perspective of
      both carers and general practitioners (GPs), and to assess whether family burden,
      as defined by the GP, is associated with hospitalisation. METHODS: A cross
      sectional nationwide survey among GPs and family carers was performed.
      Participants were 194 GPs and 74 family carers of patients who died non-suddenly.
      Additionally, in-depth interviews were conducted with 18 family carers. For the
      quantitative analyses descriptive statistics, weighted Kappa and multivariate
      logistic regression analysis was performed. For the qualitative part thematic
      analysis was conducted. RESULTS: The proportion of family carers experiencing a
      fairly heavy or severe burden increased significantly from 32% (second and third
      months before death) to 66% (one week before death). Most carers (95%) felt an
      emotional burden and 29% felt a physical burden in the final week. Three-quarters
      of carers did not perceive their burden as a problem because caring often felt
      rewarding. No significant association was found between the characteristics of
      family caregivers or professional care and the degree of family caregiver burden.
      Also, there was no significant evidence that patients of family carers for whom
      the GP assessed a fairly heavy to severe burden, were more likely to be
      hospitalised. CONCLUSIONS: The different overall assessment of family carers'
      burden between GPs and family carers and the increasing emotional and physical
      burden of family carers towards the end constitute relevant information for GPs
      that will help them understand and anticipate carers' personal needs.

PMID- 24678943
TI  - The unit size effect of indulgent food: how eating smaller sized items signals
      impulsivity and makes consumers eat less.
AB  - In deciding how much to eat, people are influenced by environmental cues. The
      unit size of food (i.e., the number of units in which a given amount of food is
      divided) provides such a cue. Previous research showed that given equal caloric
      and volumetric content, smaller units of food tend to reduce food consumption. We
      propose that the unit size of food impacts intake as it influences perceptions of
      impulsiveness and appropriateness. Our analysis is based on three experimental
      studies, all employing between subject designs. When consuming similar amounts of
      chocolates in studies 1 (n = 118) and 2 (n = 124), both studies show that
      consumption of five small units of chocolates is considered to be more impulsive,
      excessive and less appropriate than consuming one large unit of chocolate.
      Results of a third study (n = 165) indicate that about 23% less chocolate is
      eaten when it is presented in small unit size vs. a large unit size and this
      effect is mediated by perceptions of impulsivity. All three studies suggest that
      perceptions of impulsivity and excess eating while eating several smaller units
      of food compared to one large unit might be a key factor explaining consumption
      effects in earlier studies on this bias.

PMID- 24678942
TI  - The association between renal stone disease and cholesterol gallstones: the easy
      to believe and not hard to retrieve theory of the metabolic syndrome.
AB  - Renal stone disease and gallstone disease are widely prevalent and costly disease
      across the globe. Both renal stone disease and gallstone disease are associated
      with a variety of diseases including obesity, metabolic syndrome, dyslipidemia,
      hypertension, insulin resistance diabetes and gout. Importantly, the presence of
      either renal stone disease or gallstone disease is associated with an increased
      risk of cardiovascular disease. In a recent study of the Atherosclerosis Risk in
      Communities (ARIC), individuals with a history of gallstones were 54% more likely
      to report a history of nephrolithiasis after adjusting for age, gender, body size
      and other factors. Furthermore, in three large cohorts including over 240,000
      subjects: the Nurses' Health Studies (NHS) I and II and the Health Professionals
      Follow-up Study (HPFS), showed that gallstone disease is independently associated
      with nephrolithiasis. The mechanisms linking gallstone disease and renal stone
      disease are complex and not yet established. Insulin resistance, lithogenic
      diets, alterations of transporters in gallbladder and urinary system, and pH are
      possible potential mechanisms for future exploration. How the liver communicates
      with kidney in individuals with renal stone disease and gallstone disease is not
      well known and whether this communication is similar as in hepto-renal syndrome
      is subject for future research. Further research is needed to determine: (i) the
      underlying mechanisms of renal stone disease and gallstone disease; (ii) the
      potential treatment of renal stone disease and gallstone disease.

PMID- 24678939
TI  - A controlled trial of renal denervation for resistant hypertension.
AB  - BACKGROUND: Prior unblinded studies have suggested that catheter-based renal
      artery denervation reduces blood pressure in patients with resistant
      hypertension. METHODS: We designed a prospective, single-blind, randomized, sham
      controlled trial. Patients with severe resistant hypertension were randomly
      assigned in a 2:1 ratio to undergo renal denervation or a sham procedure. Before
      randomization, patients were receiving a stable antihypertensive regimen
      involving maximally tolerated doses of at least three drugs, including a
      diuretic. The primary efficacy end point was the change in office systolic blood
      pressure at 6 months; a secondary efficacy end point was the change in mean 24
      hour ambulatory systolic blood pressure. The primary safety end point was a
      composite of death, end-stage renal disease, embolic events resulting in end
      organ damage, renovascular complications, or hypertensive crisis at 1 month or
      new renal-artery stenosis of more than 70% at 6 months. RESULTS: A total of 535
      patients underwent randomization. The mean (+/-SD) change in systolic blood
      pressure at 6 months was -14.13+/-23.93 mm Hg in the denervation group as
      compared with -11.74+/-25.94 mm Hg in the sham-procedure group (P<0.001 for both
      comparisons of the change from baseline), for a difference of -2.39 mm Hg (95%
      confidence interval [CI], -6.89 to 2.12; P=0.26 for superiority with a margin of
      5 mm Hg). The change in 24-hour ambulatory systolic blood pressure was -6.75+/
      15.11 mm Hg in the denervation group and -4.79+/-17.25 mm Hg in the sham
      procedure group, for a difference of -1.96 mm Hg (95% CI, -4.97 to 1.06; P=0.98
      for superiority with a margin of 2 mm Hg). There were no significant differences
      in safety between the two groups. CONCLUSIONS: This blinded trial did not show a
      significant reduction of systolic blood pressure in patients with resistant
      hypertension 6 months after renal-artery denervation as compared with a sham
      control. (Funded by Medtronic; SYMPLICITY HTN-3 ClinicalTrials.gov number,
      NCT01418261.).

PMID- 24678944
TI  - Combining irbesartan and trichlormethiazide enhances blood pressure reduction via
      inhibition of sympathetic activity without adverse effects on metabolism in
      hypertensive rats with metabolic syndrome.
AB  - Sympathoexcitation and oxidative stress in the brain have pivotal roles in
      hypertension with metabolic syndrome (MetS). Here, we examined whether oral
      administration of irbesartan (IRB) and trichlormethiazide (TCM) decreases blood
      pressure (BP) via inhibiting sympathetic activity through anti-oxidant effects in
      the brain of spontaneously hypertensive rats (SHR-cp). IRB/TCM treatment
      decreased BP more profoundly than IRB monotherapy. Urinary norepinephrine
      excretion and oxidative stress in the brain were decreased in both IRB and
      IRB/TCM groups without any adverse effect on the metabolic profile. These
      findings suggest that IRB/TCM profoundly decreases BP in SHR-cp by inhibiting
      sympathetic activity via anti-oxidant effects in the brain.

PMID- 24678945
TI  - Septo-optic dysplasia plus: a case report.
AB  - BACKGROUND: Septo-optic dysplasia, also referred to as de Morsier syndrome, is a
      congenital condition characterized by classic triad features: midline brain
      abnormalities, optic nerve hypoplasia and pituitary endocrine dysfunction.
      Sometimes, other various malformations appear within syndrome. CASE PRESENTATION:
      An 11 and 1/2-year-old Caucasian Southeast European female patient with earlier
      established diagnoses of growth hormone deficiency, diabetes insipidus, seizures,
      mental retardation, optic nerve atrophy and right ptosis, was directed to us for
      consultative examination.The girl of short stature and low weight for her age had
      bilateral optic nerve hypoplasia, poor vision, nystagmus and right eye oculomotor
      palsy. Electroencephalogram revealed epileptic changes. Magnetic resonance
      imaging showed an empty sella syndrome, partial hypoplasia of corpus callosum,
      cavum of pellucid septum and diffuse polymicrogyria of the left temporal lobe. We
      found all elements of septo-optic dysplasia plus syndrome with right oculomotor
      nerve involvement. CONCLUSION: By earlier findings and evaluation, we established
      a diagnosis of septo-optic dysplasia plus. The case confirms the existence of
      various malformations within the syndrome and the need for the cooperation of
      several specialists in the diagnosis and treatment of children with the syndrome.

PMID- 24678937
TI  - Transcatheter aortic-valve replacement with a self-expanding prosthesis.
AB  - BACKGROUND: We compared transcatheter aortic-valve replacement (TAVR), using a
      self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic
      valve replacement in patients with severe aortic stenosis and an increased risk
      of death during surgery. METHODS: We recruited patients with severe aortic
      stenosis who were at increased surgical risk as determined by the heart team at
      each study center. Risk assessment included the Society of Thoracic Surgeons
      Predictor Risk of Mortality estimate and consideration of other key risk factors.
      Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self
      expanding transcatheter valve (TAVR group) or to surgical aortic-valve
      replacement (surgical group). The primary end point was the rate of death from
      any cause at 1 year, evaluated with the use of both noninferiority and
      superiority testing. RESULTS: A total of 795 patients underwent randomization at
      45 centers in the United States. In the as-treated analysis, the rate of death
      from any cause at 1 year was significantly lower in the TAVR group than in the
      surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9
      percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001
      for noninferiority; P = 0.04 for superiority). The results were similar in the
      intention-to-treat analysis. In a hierarchical testing procedure, TAVR was
      noninferior with respect to echocardiographic indexes of valve stenosis,
      functional status, and quality of life. Exploratory analyses suggested a
      reduction in the rate of major adverse cardiovascular and cerebrovascular events
      and no increase in the risk of stroke. CONCLUSIONS: In patients with severe
      aortic stenosis who are at increased surgical risk, TAVR with a self-expanding
      transcatheter aortic-valve bioprosthesis was associated with a significantly
      higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded
      by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number,
      NCT01240902.).

PMID- 24678946
TI  - New insights into the dual fluorescence of methyl salicylate: effects of
      intermolecular hydrogen bonding and solvation.
AB  - In this paper, we propose a new and complete mechanism for dual fluorescence of
      methyl salicylate (MS) under different conditions using a combined experimental
      (i.e., steady-state absorption and emission spectra and time-resolved
      fluorescence spectra) and theoretical (i.e., time-dependent density function
      theory) study. First, our theoretical study indicates that the barrier height for
      excited state intramolecular proton transfer (ESIPT) reaction of ketoB depends on
      the solvent polarity. In nonpolar solvents, the ESIPT reaction of ketoB is
      barrierless; the barrier height will increase with increasing solvent polarity.
      Second, we found that, in alcoholic solvents, intermolecular hydrogen bonding
      plays a more important role. The ketoB form of MS can form two hydrogen bonds
      with alcoholic solvents; one will facilitate ESIPT and produce the emission band
      in the blue region; the other one precludes ESIPT and produces the emission band
      in the near-UV region. Our proposed new mechanism can well explain previous
      results as well as our new experimental results. 

PMID- 24678947
TI  - Identification and characterization of small molecule modulators of the Epstein
      Barr virus-induced gene 2 (EBI2) receptor.
AB  - Oxysterols have recently been identified as natural ligands for a G protein
      coupled receptor called EBI2 (aka GPR183) ( Nature 2011 , 475 , 524 ; 519 ). EBI2
      is highly expressed in immune cells ( J. Biol. Chem. 2006 , 281 , 13199 ), and
      its activation has been shown to be critical for the adaptive immune response and
      has been genetically linked to autoimmune diseases such as type I diabetes (
      Nature 2010 , 467 , 460 ). Here we describe the isolation of a potent small
      molecule antagonist for the EBI2 receptor. First, we identified a small molecule
      agonist NIBR51 (1), which enabled identification of inhibitors of receptor
      activation. One antagonist called NIBR127 (2) was used as a starting point for a
      medicinal chemistry campaign, which yielded NIBR189 (4m). This compound was
      extensively characterized in binding and various functional signaling assays.
      Furthermore, we have used 4m to block migration of a monocyte cell line called
      U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune
      cells. 

PMID- 24678949
TI  - Thermo-responsive diblock copolymer worm gels in non-polar solvents.
AB  - Benzyl methacrylate (BzMA) is polymerized using a poly(lauryl methacrylate)
      macromolecular chain transfer agent (PLMA macro-CTA) using reversible addition
      fragmentation chain transfer (RAFT) polymerization at 70  degrees C in n
      dodecane. This choice of solvent leads to an efficient dispersion polymerization,
      with polymerization-induced self-assembly (PISA) occurring via the growing PBzMA
      block to produce a range of PLMA-PBzMA diblock copolymer nano-objects, including
      spheres, worms, and vesicles. In the present study, particular attention is paid
      to the worm phase, which forms soft free-standing gels at 20  degrees C due to
      multiple inter-worm contacts. Such worm gels exhibit thermo-responsive behavior:
      heating above 50  degrees C causes degelation due to the onset of a worm-to
      sphere transition. Degelation occurs because isotropic spheres interact with each
      other much less efficiently than the highly anisotropic worms. This worm-to
      sphere thermal transition is essentially irreversible on heating a dilute
      solution (0.10% w/w) but is more or less reversible on heating a more
      concentrated dispersion (20% w/w). The relatively low volatility of n-dodecane
      facilitates variable-temperature rheological studies, which are consistent with
      eventual reconstitution of the worm phase on cooling to 20  degrees C. Variable
      temperature (1)H NMR studies conducted in d26-dodecane confirm partial solvation
      of the PBzMA block at elevated temperature: surface plasticization of the worm
      cores is invoked to account for the observed change in morphology, because this
      is sufficient to increase the copolymer curvature and hence induce a worm-to
      sphere transition. Small-angle X-ray scattering and TEM are used to investigate
      the structural changes that occur during the worm-to-sphere-to-worm thermal
      cycle; experiments conducted at 1.0 and 5.0% w/w demonstrate the concentration
      dependent (ir)reversibility of these morphological transitions. 

PMID- 24678948
TI  - Contribution of subcutaneous abdominal fat on ultrasonography to carotid
      atherosclerosis in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Whereas visceral abdominal adipose tissue (VAT) is associated with
      cardiometabolic risk, there is debate regarding the role of subcutaneous
      abdominal adipose tissue (SAT). The aim of this study was to investigate the
      relationships of subcutaneous and visceral abdominal fat with carotid
      atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS: A
      total of 234 patients (men 131, women 103, mean age: 53 years) with T2DM were
      enrolled. Carotid intima-media thickness (CIMT), abdominal subcutaneous fat
      thickness (SFT) and visceral fat thickness (VFT) were assessed by high-resolution
      B-mode ultrasonography (US). RESULTS: Compared to women, men had significantly
      higher VFT and lower SFT (p = 0.002, p = 0.04, respectively). In partial
      correlation coefficient analyses between CIMT and abdominal fat thickness after
      adjustment for body mass index (BMI), SFT showed a negative correlation with CIMT
      in men (r = -0.27, p = 0.03). VFT was not correlated with CIMT in either men or
      women. In women, SFT was not correlated with CIMT (r = -0.01, p = 0.93). VFT/SFT
      ratio was not correlated with CIMT in either men or women. In multivariate
      regression analyses adjusted for BMI and other CVD risk factors, SFT but not VFT
      was independently inversely associated with CIMT in men but not in women (p <
      0.001). CONCLUSIONS: SFT assessed by US was inversely associated with carotid
      atherosclerosis in patients with T2DM, particularly men. Further research into
      the different roles of the two types of abdominal adipose tissue in both men and
      women is warranted.

PMID- 24678950
TI  - Facile and precise formation of unsymmetric vesicles using the helix dipole,
      stereocomplex, and steric effects of peptides.
AB  - Unsymmetrical vesicular membranes were prepared from a binary mixture of the A3B
      type and the AB-type host polypeptides, which were composed of the hydrophilic
      block (A) and the hydrophobic helical block (B) but with a different helix sense
      between the two host polypeptides. TEM and DLS revealed the formation of vesicles
      with ca. 100 nm diameter. The molecular assembly was driven by hydrophobic
      interaction, stereocomplex formation, and dipole-dipole interaction between
      hydrophobic helices. Furthermore, the A3B-type host polypeptide extended the
      hydrophilic block to the outer surface of vesicles as a result of the steric
      effect, resulting in the formation of unsymmetrical vesicular membranes. As a
      result, a functionalized AB-type guest polypeptide having the same helix sense
      with the A3B-type host polypeptide exposed the hydrophilic block to the outer
      surface. In contrast, an AB-type guest polypeptide having the same helix sense
      with the AB-type host polypeptide oriented the hydrophilic block to the inner
      surface. Functionalization of either the outer or inner surface of the binary
      vesicle is therefore facile to achieve when using either the right- or the left
      handed helix of the functionalized guest polypeptide. 

PMID- 24678951
TI  - Dehiscence of detached internal limiting membrane in eyes with myopic traction
      maculopathy with spontaneous resolution.
AB  - BACKGROUND: To report the optical coherence tomographic (OCT) findings in 4 eyes
      before and after a spontaneous resolution of a myopic traction maculopathy (MTM).
      METHOD: Retrospective review of medical records including history, examination
      findings, fundus details, and finding of spectral-domain OCT (Cirrus HD-OCT, Carl
      Zeiss Meditec, Spectralis, Heidelberg Engineering, Heidelberg) findings in 4 eyes
      with a spontaneous resolution of MTM. RESULTS: A release of the vitreofoveal
      traction was detected by OCT in 3 eyes before the resolution of the MTM. A
      vitreofoveal separation in one eye and an increase in the length of a vitreous
      strand from the macula in two eyes indicated a reduction in the traction. In 2
      eyes, an internal limiting membrane (ILM) detachment was seen by OCT as a
      membrane above the wrinkled inner retina at the perifoveal lesion, and a
      flattening of the ILM and inner retina was detected after the resolution. The
      detached ILM was shifted centrifugally on the macula and disappeared with the
      flattening of the adjacent retina which suggests that the release of tangential
      traction was caused by the dehiscence of ILM possibly at the proximal edges of
      the ILM detachment. CONCLUSION: Releasing a vitreofoveal traction and flattening
      of the detached ILM may be signs of spontaneous resolution of a MTM. Vitrectomy
      is not required when these signs are detected.

PMID- 24678952
TI  - Multiple primary malignancies of the liver and the colon: a complex diagnostic
      and decisional process with a final unanswered question.
AB  - We herein present the case of a 78-year-old man with an incidental finding of a
      solid hepatic mass without symptoms and only a laparotomic cholecystectomy for
      acute cholecystitis in the past surgical history. A colonoscopy, a magnetic
      resonance imaging scan, a positron emission tomography scan, and a computed
      tomography scan completed the preoperative workup: a neoplastic lesion 4.3*3 cm
      in size was diagnosed at segments IV and V, associated with a neoplastic
      involvement of the splenic flexure without signs of colonic occlusion. After
      colonic resection, a frozen section on a granulomatous-like tissue at gastric
      border suggested a diagnosis of an adenocarcinoma of bilio-pancreatic type,
      changing the surgical strategy to include gastric resection and hepatic pedicle
      node dissection. The discussion turns around the idea that a final diagnosis of
      colon cancer with regional nodal involvement (pT3N1) and metastatic gallbladder
      cancer with multiple peritoneal seedings cannot be excluded.

PMID- 24678953
TI  - Is the dissociative adult suggestible? A test of the trauma and fantasy models of
      dissociation.
AB  - Psychologists have long assumed a connection between traumatic experience and
      psychological dissociation. This hypothesis is referred to as the trauma model of
      dissociation. In the past decade, a series of papers have been published that
      question this traditional causal link, proposing an alternative fantasy model of
      dissociation. In the present research, the relationship among dissociation,
      suggestibility, and fantasy proneness was examined. Suggestibility was measured
      through the Gudjonsson Scale of Interrogative Suggestibility (GSS) as well as an
      autobiographically based version of this measure based on the events of September
      11, 2001. Consistent with prior research and with the trauma model, dissociation
      correlated positively with trauma severity (r = .32, p < .01) and fantasy
      proneness (r = .60, p < .01). Inconsistent with the fantasy model, dissociation
      did not correlate with the neutral form of the GSS and correlated negatively (r =
      -.24, p < .05) with the trauma-focused form of this suggestibility measure.
      Although some participants did become quite emotional during the procedure, the
      risk/benefit ratio was perceived by almost all participants to be positive, with
      more reactive individuals evaluating the procedure more positively. The results
      consistently support the trauma model of dissociation and fail to support the
      fantasy model of dissociation. 

PMID- 24678954
TI  - Visual ModuleOrganizer: a graphical interface for the detection and comparative
      analysis of repeat DNA modules.
AB  - BACKGROUND: DNA repeats, such as transposable elements, minisatellites and
      palindromic sequences, are abundant in sequences and have been shown to have
      significant and functional roles in the evolution of the host genomes. In a
      previous study, we introduced the concept of a repeat DNA module, a flexible
      motif present in at least two occurences in the sequences. This concept was
      embedded into ModuleOrganizer, a tool allowing the detection of repeat modules in
      a set of sequences. However, its implementation remains difficult for larger
      sequences. RESULTS: Here we present Visual ModuleOrganizer, a Java graphical
      interface that enables a new and optimized version of the ModuleOrganizer tool.
      To implement this version, it was recoded in C++ with compressed suffix tree data
      structures. This leads to less memory usage (at least 120-fold decrease in
      average) and decreases by at least four the computation time during the module
      detection process in large sequences. Visual ModuleOrganizer interface allows
      users to easily choose ModuleOrganizer parameters and to graphically display the
      results. Moreover, Visual ModuleOrganizer dynamically handles graphical results
      through four main parameters: gene annotations, overlapping modules with known
      annotations, location of the module in a minimal number of sequences, and the
      minimal length of the modules. As a case study, the analysis of FoldBack4
      sequences clearly demonstrated that our tools can be extended to comparative and
      evolutionary analyses of any repeat sequence elements in a set of genomic
      sequences. With the increasing number of sequences available in public databases,
      it is now possible to perform comparative analyses of repeated DNA modules in a
      graphic and friendly manner within a reasonable time period. AVAILABILITY: Visual
      ModuleOrganizer interface and the new version of the ModuleOrganizer tool are
      freely available at: http://lcb.cnrs-mrs.fr/spip.php?rubrique313.

PMID- 24678956
TI  - Organic pollutant clustered in the plant cuticular membranes: visualizing the
      distribution of phenanthrene in leaf cuticle using two-photon confocal scanning
      laser microscopy.
AB  - Plants play a key role in the transport and fate of organic pollutants. Cuticles
      on plant surfaces represent the first resistance for the uptake of airborne
      toxicants. In this study, a confocal scanning microscope enhanced with a two
      photon laser was applied as a direct and noninvasive probe to explore the in situ
      uptake of a model pollutant, phenanthrene (PHE), into the cuticular membrane of a
      hypostomatic plant, Photinia serrulata. On the leaf cuticle surfaces, PHE forms
      clusters instead of being evenly distributed. The PHE distribution was quantified
      by the PHE fluorescence intensity. When PHE concentrations in water varying over
      5 orders of magnitude were applied to the isolated cuticle, the accumulated PHE
      level by the cuticle was not vastly different, whether PHE was applied to the
      outer or inner side of the cuticle. Notably, PHE was found to diffuse via a
      channel-like pathway into the middle layer of the cuticle matrix, where it was
      identified to be composed of polymeric lipids. The strong affinity of PHE for
      polymeric lipids is a major contributor of the fugacity gradient driving the
      diffusive uptake of PHE in the cuticular membrane. Membrane lipids constitute
      important domains for hydrophobic interaction with pollutants, determining
      significant differentials of fugacities within the membrane microsystem. These,
      under unsteady conditions, contribute to enhance net transport and clustering
      along the z dimension. Moreover, the liquid-like state of polymeric lipids may
      promote mobility by enhancing the diffusion rate. The proposed "diffusive uptake
      and storage" function of polymeric lipids within the membrane characterizes the
      modality of accumulation of the hydrophobic contaminant at the interface between
      the plant and the environment. Assessing the capacity of fugacity of these
      constituents in detail will bring about knowledge of contaminant fate in superior
      plants with a higher level of accuracy. 

PMID- 24678957
TI  - Meningioangiomatosis in a second trimester fetus.
AB  - We describe to our knowledge the first case of meningioangiomatosis identified in
      a second trimester fetus. A 30-year-old pregnant woman was attended at our
      hospital for a second-trimester ultrasound screening scan. With a diagnosis of
      partial agenesis of the corpus callosum, the parents requested termination of the
      pregnancy. At autopsy, frontal serial sections of the fetal brain disclosed a
      short corpus callosum that lacked the posterior splenium, confirming the
      sonographic diagnosis. At close inspection, a slight bilateral hardening of both
      medial aspects of the frontal lobes and anterior genu of the corpus callosum was
      found associated with meningeal adhesion between both frontal lobes.
      Microscopically, cerebral cortex and corpus callosum were permeated by
      intersecting bundles of spindle cells with eosinophilic cytoplasm and bland,
      round nuclei, with a fibroblast or meningothelial-like appearance surrounding
      abundant blood vessels, consistent with the diagnosis of meningioangiomatosis.
      According to this finding, meningioangiomatosis must be included in the
      differential diagnosis of meningocortical fetal lesions.

PMID- 24678958
TI  - Prognostic value of miR-96 in patients with acute myeloid leukemia.
AB  - OBJECTIVE: Aberrant expression of miRNA (miR)-96 is associated with tumorigenesis
      and tumor progression in several solid cancers. However, little is known about
      the expression and prognostic value of miR-96 in acute myeloid leukemia (AML).
      Therefore, the aim of this study was to investigate the correlation of miR-96
      expression with clinicopathological features and prognosis of AML. METHODS: Real
      time quantitative RT-PCR assay was performed to evaluate the expression levels of
      miR-96 in mononuclear cells from bone marrow or peripheral blood specimens in 86
      patients with newly diagnosed AML. RESULTS: Compared with normal controls, miR-96
      expression was significantly downregulated in patients with newly diagnosed AML
      (P < 0.001). In analysis of 14 diagnosis/CR-paired samples, the expression level
      of miR-96 was found markedly elevated in patients after treatment than before (P
      < 0.001). Moreover, lower levels of miR-96 were associated with a higher white
      blood cell count, bone marrow blast count (P < 0.001 and 0.022, respectively),
      and lower hemoglobin and platelet count (P = 0.036 and 0.033, respectively).
      Although the low-expression group seemed to have a lower CR rate (53.85% vs
      70.0%), there was no significant difference between the two groups (P = 0.213).
      The low-expression group had a lower relapse-free survival (RFS) (P = 0.038) and
      overall survival (OS) (P = 0.022) compared with the high-expression group during
      a median follow-up of 20 months. CONCLUSION: Our data demonstrated that the
      expression of miR-96 was downregulated in newly diagnosed AML patients and
      associated with leukemic burden, as well as RFS and OS. This suggests that miR-96
      detection might become a potential biomarker of prognosis and monitoring in AML.
      VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1434808553949498.

PMID- 24678960
TI  - Dynamic acoustic control of individual optically active quantum dot-like emission
      centers in heterostructure nanowires.
AB  - We probe and control the optical properties of emission centers forming in radial
      heterostructure GaAs-Al0.3Ga0.7As nanowires and show that these emitters, located
      in Al0.3Ga0.7As layers, can exhibit quantum-dot like characteristics. We employ a
      radio frequency surface acoustic wave to dynamically control their emission
      energy, and occupancy state on a nanosecond time scale. In the spectral
      oscillations, we identify unambiguous signatures arising from both the mechanical
      and electrical component of the surface acoustic wave. In addition, different
      emission lines of a single emission center exhibit pronounced anticorrelated
      intensity oscillations during the acoustic cycle. These arise from a dynamically
      triggered carrier extraction out of the emission center to a continuum in the
      radial heterostructure. Using finite element modeling and Wentzel-Kramers
      Brillouin theory we identify quantum tunneling as the underlying mechanism. These
      simulation results quantitatively reproduce the observed switching and show that
      in our systems these emission centers are spatially separated from the continuum
      by >10.5 nm. 

PMID- 24678959
TI  - The development and initial validation of the narrative foreclosure scale.
AB  - OBJECTIVES: As people grow older, identity development in later life becomes a
      more and more relevant topic. Studying processes that hinder or promote identity
      development in later life is of importance. Within this broader field, there has
      been a growing interest in narrative foreclosure. Our goal was to develop a
      short, reliable and easy-to-use instrument measuring narrative foreclosure and to
      validate this instrument in two samples. METHODS: The narrative foreclosure scale
      (NFS) was validated in two studies with a sample of middle-aged adults (n = 319)
      and a sample with older adults (n = 174). Several analyses were conducted to
      assess the psychometric properties, the factor-structure and incremental validity
      of the scale. RESULTS: Confirmatory factor analyses generally showed an
      acceptable fit of the two-factor (NF-Future and NF-Past) model to the data in
      both samples. Both factors of the NFS demonstrated adequate to good internal
      consistency, with alpha coefficients ranging from .79 for NF-Past in study 2 to
      .88 for NF-Future in study 1. Construct validity was good as shown by moderate to
      large correlations to related constructs. The scale adds a unique portion of
      explained variance to positive mental health, thereby showing the incremental
      validity of the NFS. CONCLUSION: A reliable scale is now available that allows to
      study the premature hindering of identity development in older populations. The
      use of the NFS as a process measure in studies on the effectiveness of
      interventions aiming at meaning making and identity development, such as life
      review therapy and narrative therapy, is also recommended.

PMID- 24678961
TI  - Sleep and technology: not always strange bedfellows.

PMID- 24678962
TI  - NAD attenuates oxidative DNA damages induced by amyloid beta-peptide in primary
      rat cortical neurons.
AB  - One major pathological hallmark of Alzheimer's disease (AD) is accumulation of
      senile plaques in patients' brains, mainly composed of amyloid beta-peptide
      (Abeta). Nicotinamide adenine dinucleotide (NAD) has emerged as a common mediator
      regulating energy metabolism, mitochondrial function, aging, and cell death, all
      of which are critically involved in neuronal demise observed in AD. In this work,
      we tested the hypothesis that NAD may attenuate Abeta-induced DNA damages,
      thereby conferring neuronal resistance to primary rat cortical cultures. We found
      that co-incubation of NAD dose-dependently attenuated neurotoxicity mediated by
      Abeta25-35 and Abeta1-42 in cultured rat cortical neurons, with the optimal
      protective dosage at 50 mM. NAD also abolished the formation of reactive oxygen
      species (ROS) induced by Abeta25-35. Furthermore, Abetas were capable of inducing
      oxidative DNA damages by increasing the extents of 8-hydroxy-2'-deoxyguanosine (8
      OH-dG), numbers of apurinic/apyrimidinic (AP) sites, genomic DNA single-stranded
      breaks (SSBs), as well as DNA double-stranded breaks (DSBs)/fragmentation, which
      can all be attenuated upon co-incubation with NAD. Our results thus reveal a
      novel finding that NAD is protective against DNA damage induced by existing
      Abeta, leading ultimately to neuroprotection in primary cortical culture.

PMID- 24678963
TI  - Measurement of endotracheal tube secretions volume by micro computed tomography
      (MicroCT) scan: an experimental and clinical study.
AB  - BACKGROUND: Biofilm accumulates within the endotracheal tube (ETT) early after
      intubation. Contaminated secretions in the ETT are associated with increased risk
      for microbial dissemination in the distal airways and increased resistance to
      airflow. We evaluated the effectiveness of micro computed tomography (MicroCT)
      for the quantification of ETT inner volume reduction in critically ill patients.
      METHODS: We injected a known amount of gel into unused ETT to simulate
      secretions. We calculated the volume of gel analyzing MicroCT scans for a length
      of 20 cm. We then collected eleven ETTs after extubation of critically ill
      patients, recording clinical and demographical data. We assessed the amount of
      secretions by MicroCT and obtained ETT microbiological cultures. RESULTS: Gel
      volumes assessed by MicroCT strongly correlated with injected gel volumes (p <
      0.001, r2 = 0.999).MicroCT revealed the accumulation of secretions on all the
      ETTs (median 0.154, IQR:0.02-0.837 mL), corresponding to an average cross
      sectional area reduction of 1.7%. The amount of secretions inversely correlated
      with patients' age (p = 0.011, rho = -0.727) but not with days of intubation,
      SAPS2, PaO2/FiO2 assessed on admission. Accumulation of secretions was higher in
      the cuff region (p = 0.003). Microbial growth occurred in cultures from 9/11
      ETTs, and did not correlate with secretions amount. In 7/11 cases the same
      microbes were identified also in tracheal aspirates. CONCLUSIONS: MicroCT appears
      as a feasible and precise technique to measure volume of secretions within ETTs
      after extubation. In patients, secretions tend to accumulate in the cuff region,
      with high variability among patients.

PMID- 24678964
TI  - Prevalence, impacts and medical managements of premenstrual syndrome among female
      students: cross-sectional study in College of Health Sciences, Mekelle
      University, Mekelle, northern Ethiopia.
AB  - BACKGROUND: Premenstrual syndrome (PMS) is used to describe physical, cognitive,
      affective, and behavioral symptoms that occur cyclically during the luteal phase
      of the menstrual cycle and resolve quickly at or within a few days of the onset
      of menstruation. The primary aim of the study was to assess the prevalence,
      impacts and medical managements of PMS on female medical students of Mekelle
      University College of Health Sciences. METHODS: A cross-sectional study was
      conducted among systematically selected female students of Mekelle University
      College of Health Sciences, Mekelle town, northern Ethiopia from March to April
      2013. A structured and pretested self-administered questionnaire was employed for
      data collection. The collected data were analyzed using the Statistical Package
      for the Social Sciences, SPSS Inc., Chicago, IL (SPSS version 16). The criteria
      proposed by the Diagnostic and Statistical Manual of Mental Disorders, fourth
      edition, text revision (DSM-IV TR) were used to diagnose PMS. RESULT: From the
      total population size of 608; a sample size of 258 was drawn. Age of the study
      participants ranged from 18 to 25 years, with mean age of 20.86 +/- 1.913 years.
      Among the participants, 144(83.2%) have had at least one PM symptoms with their
      menstrual period. The prevalence of PMS according to DSM-IV was 37.0%. About
      49(28.3%) reported frequent class missing, 17(9.8%) exam missing, 14(8.1%) low
      grade scoring and 3(1.7%) of them reported withdrawal from their learning
      associated with their PMS. Only 83(48.0%) participants sought medical treatment
      for their PMS. The treatment modalities used were pain killers, 63(36.4%), hot
      drinks like coffee and tea, 13(7.5%), and massage therapy and exercise, 7(4.0%).
      Binary logistic regression analysis revealed average length of one cycle of
      menstruation (COR = 0.20(0.070-0.569) and academic performance impairment (AOR =
      0.345(0.183-0.653) were significantly associated with the diagnosis of PMS and
      use of PMS treatments respectively. CONCLUSIONS: Our study revealed a high
      prevalence and negative impact of PMS on students of Mekelle University.
      Therefore, health education, appropriate medical treatment and counseling
      services, as part of the overall health service, should be availed and provided
      to affected women.

PMID- 24678965
TI  - Benefit of azilsartan on blood pressure elevation around rest-to-active phase in
      spontaneously hypertensive rats.
AB  - Abnormal elevation of blood pressure in early morning (rest-to-active phase) is
      suggested to cause cardiovascular events. We investigated whether azilsartan
      (AZL), a novel potent angiotensin receptor blocker, suppresses blood pressure
      elevation from the light-rest to dark-active phase in spontaneously hypertensive
      rats (SHRs). AZL has a sustained depressor effect around the rest-to-active phase
      in SHRs to a greater extent than candesartan (CAN), despite their similar
      depressor effects for over 24 h. AZL did not cause sympathoexcitation. These
      results suggest that AZL has a more sustained depressor effect than CAN around
      the rest-to-active phase in SHRs, and might have advantages for early morning
      hypertension.

PMID- 24678966
TI  - Examining electrostatic preorganization in monoamine oxidases A and B by
      structural comparison and pKa calculations.
AB  - Monoamine oxidases (MAO) A and B are important flavoenzymes involved in the
      metabolism of amine neurotransmitters. Orru et al. ( J. Neural Transm. 2013 , 120
      , 847 - 851 ) recently presented experimental results that have challenged the
      prevailing assumption that MAO A and MAO B employ an identical catalytic
      mechanism. We compared the spatial configuration of ionizable groups in both
      isozymes and estimated the time-averaged electrostatic potential by calculating
      the pKa values of five active site residues. Superimposition of both experimental
      structures shows very close overlap and the RMSD in placements of ionizable
      groups within 16 A of the reaction center is only 0.847 A. This similarity is
      also reflected in the calculated pKa values, where the largest difference between
      the MAO A and MAO B pKa values was found for residues Tyr188 in MAO B and the
      corresponding Tyr197 in MAO A assuming 1.23 units. The pKa values for the other
      four studied residues differ by less than 0.75 units. The results show that the
      electrostatic preorganizations in both active sites are very similar, supporting
      the idea that both enzymes work by the same mechanism. 

PMID- 24678967
TI  - Lung capillary injury and repair in left heart disease: a new target for therapy?
AB  - The lungs are the primary organs affected in LHD (left heart disease). Increased
      left atrial pressure leads to pulmonary alveolar-capillary stress failure,
      resulting in cycles of alveolar wall injury and repair. The reparative process
      causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular
      matrix deposition, resulting in thickening of the alveolar wall. Although the
      resultant reduction in vascular permeability is initially protective against
      pulmonary oedema, the process becomes maladaptive causing a restrictive lung
      syndrome with impaired gas exchange. This pathological process may also
      contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have
      specifically evaluated lung structural remodelling and the effect of related
      therapies in LHD. Currently approved treatment for chronic HF (heart failure) may
      have direct beneficial effects on lung structural remodelling. In the future,
      novel therapies specifically targeting the remodelling processes may potentially
      be utilized. In the present review, we summarize data supporting the clinical
      importance and pathophysiological mechanisms of lung structural remodelling in
      LHD and propose that this pathophysiological process should be explored further
      in pre-clinical studies and future therapeutic trials. 

PMID- 24678968
TI  - Muscular activities during sling- and ground-based push-up exercise.
AB  - BACKGROUND: This study aimed to clarify the characteristics of muscle activities
      during push-up exercises performed under sling condition by comparison with those
      performed under ground condition. We hypothesized that sling-based push-ups
      induce higher muscle activities than the ground-based push-ups, and its effects
      are more prominent in dynamic compared to static exercise owing to increased
      demands of stabilization. FINDINGS: Twenty young males performed sling- and
      ground-based push-ups in each of static (maintaining the posture with the elbow
      joint angle at 90 deg) and dynamic (repeating push-ups at a rate of 45 per
      minute) exercises. Surface electromyograms (EMGs) of the pectoralis major,
      latissimus dorsi, triceps brachii, biceps brachii, rectus abdominis, external
      oblique, internal oblique, and erector spinae muscles were recorded during the
      exercises. The EMG data were normalized to those obtained during maximal
      voluntary contraction of each muscle (% EMGmax). In the static exercise, sling
      condition showed significantly higher % EMGmax values than the ground condition
      in the triceps brachii (+27%: relative to ground condition) and biceps brachii
      (+128%) as well as the three abdominal muscles (+15% to +27%). In the dynamic
      exercise, such condition-related differences were more prominent and those in the
      pectoralis major (+29%) in addition to the aforementioned five muscles (+19% to
      +144%) were significant. CONCLUSION: These results supported the hypothesis and
      indicate that sling-based push-up exercise can provide greater activation in
      upper limb and anterior trunk muscles than the ground-based push-up exercise.

PMID- 24678969
TI  - Discovery of a novel series of orally active nociceptin/orphanin FQ (NOP)
      receptor antagonists based on a dihydrospiro(piperidine-4,7'-thieno[2,3-c]pyran)
      scaffold.
AB  - Nociceptin/OFQ (N/OFQ) is a 17 amino acid peptide that is the endogenous ligand
      for the ORL1/NOP receptor. Nociceptin appears to regulate a host of physiological
      functions such as biological reactions to stress, anxiety, mood, and drug abuse,
      in addition to feeding behaviors. To develop tools to study the function of
      nociceptin and NOP receptor, our research effort sought to identify orally
      available NOP antagonists. Our effort led to the discovery of a novel chemical
      series based on the dihydrospiro(piperidine-4,7'-thieno[2,3-c]pyran) scaffold.
      Herein we show that dihydrospiro(piperidine-4,7'-thieno[2,3-c]pyran)-derived
      compounds are potent NOP antagonists with high selectivity versus classical
      opioid receptors (MU, delta, and kappa). Moreover, these compounds exhibit
      sufficient bioavailability to produce a high level of NOP receptor occupancy in
      the brain following oral administration in rats. 

PMID- 24678970
TI  - The effects of adenosine A2B receptor inhibition on VEGF and nitric oxide axis
      mediated renal function in diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is the most common cause of end-stage renal disease
      worldwide. The pathophysiologic mechanisms of diabetic nephropathy are
      incompletely understood but include overproduction of various growth factors and
      cytokines. Upregulation of vascular endothelial growth factor (VEGF) is a
      pathogenic event occurring in most forms of podocytopathy; however, the
      mechanisms that regulate this growth factor induction are not clearly identified.
      A2B receptors have been found to regulate VEGF expression under hypoxic
      environment in different tissues. One proposed hypothesis in mediating diabetic
      nephropathy is the modulation of VEGF-NO balance in renal tissue. We determined
      the role of adenosine A2B receptor in mediating VEGF overproduction and nitrite
      in diabetic nephropathy. The renal content of A2B receptors and VEGF was
      increased after 8 weeks of diabetes induction. The renal and plasma nitrite
      levels were also reduced in these animals. In vivo administration of A2B
      adenosine receptor antagonist (MRS1754) inhibited the renal over expression of
      VEGF and adverse renal function parameters. The antagonist administration also
      improved the kidney tissue nitrite levels. In conclusion, we demonstrated that
      VEGF induction via adenosine signaling might be the critical event in regulating
      VEGF-NO axis in diabetic nephropathy.

PMID- 24678971
TI  - Efficient assembly of threaded molecular machines for sequence-specific
      synthesis.
AB  - We report on an improved strategy for the preparation of artificial molecular
      machines that can pick up and assemble reactive groups in sequence by traveling
      along a track. In the new approach a preformed rotaxane synthon is attached to
      the end of an otherwise fully formed strand of building blocks. This "rotaxane
      capping" protocol is significantly more efficient than the "final-step-threading"
      method employed previously and enables the synthesis of threaded molecular
      machines that operate on extended oligomer, and potentially polymer, tracks. The
      methodology is exemplified through the preparation of a machine that adds four
      amino acid building blocks from a strand in sequence, featuring up to 20-membered
      ring native chemical ligation transition states. 

PMID- 24678973
TI  - Competition between anisometric and aliphatic entities: an unusual phase sequence
      with the induction of a phase in an n-alkane-liquid crystal binary system.
AB  - In this work, we demonstrate two important features that arise out of introducing
      a liquid-crystalline (LC) compound into the rotator phase matrix and the
      consequent competition between the anisometric segments of the LC moieties and
      the aliphatic units. First, we show that the change in the structural character
      of the mixed medium depends on which of the entities forms the minority
      concentration: in the case of this being the alkane, the two components of the
      binary system are nanophase segregated, whereas if the LC molecules are present
      in a small concentration, then the layered structure merely gets roughened
      without any segregation. The second and more significant result of the
      calorimetric and X-ray experiments, at low LC concentrations, is the induction of
      a rotator phase that leads to unusual phase sequence not reported hitherto.
      Possible scenarios for the molecular arrangement are discussed. A Landau model is
      also presented that explains some of the observed features. 

PMID- 24678972
TI  - Assessment of metabolic flux distribution in the thermophilic hydrogen producer
      Caloramator celer as affected by external pH and hydrogen partial pressure.
AB  - BACKGROUND: Caloramator celer is a strict anaerobic, alkalitolerant, thermophilic
      bacterium capable of converting glucose to hydrogen (H2), carbon dioxide,
      acetate, ethanol and formate by a mixed acid fermentation. Depending on the
      growth conditions C. celer can produce H2 at high yields. For a biotechnological
      exploitation of this bacterium for H2 production it is crucial to understand the
      factors that regulate carbon and electron fluxes and therefore the final
      distribution of metabolites to channel the metabolic flux towards the desired
      product. RESULTS: Combining experimental results from batch fermentations with
      genome analysis, reconstruction of central carbon metabolism and metabolic flux
      analysis (MFA), this study shed light on glucose catabolism of the thermophilic
      alkalitolerant bacterium C. celer. Two innate factors pertaining to culture
      conditions have been identified to significantly affect the metabolic flux
      distribution: culture pH and partial pressures of H2 (PH2). Overall, at alkaline
      to neutral pH the rate of biomass synthesis was maximized, whereas at acidic pH
      the lower growth rate and the less efficient biomass formation are accompanied
      with more efficient energy recovery from the substrate indicating high cell
      maintenance possibly to sustain intracellular pH homeostasis. Higher H2 yields
      were associated with fermentation at acidic pH as a consequence of the lower
      synthesis of other reduced by-products such as formate and ethanol. In contrast,
      PH2 did not affect the growth of C. celer on glucose. At high PH2 the cellular
      redox state was balanced by rerouting the flow of carbon and electrons to ethanol
      and formate production allowing unaltered glycolytic flux and growth rate, but
      resulting in a decreased H2 synthesis. CONCLUSION: C. celer possesses a flexible
      fermentative metabolism that allows redistribution of fluxes at key metabolic
      nodes to simultaneously control redox state and efficiently harvest energy from
      substrate even under unfavorable conditions (i.e. low pH and high PH2). With the
      H2 production in mind, acidic pH and low PH2 should be preferred for a high yield
      oriented process, while a high productivity-oriented process can be achieved at
      alkaline pH and high PH2.

PMID- 24678974
TI  - Use of psychotropic medication groups in people with severe mental illness and
      stressful childhood experiences.
AB  - Stressful childhood experiences (SCE) are associated with a variety of health and
      social problems. In people with severe mental illness (SMI) traumatic childhood
      experiences have been linked to more severe and treatment refractory forms of
      psychiatric symptoms, including psychotic symptoms. This study evaluates the use
      of psychotropic medication groups in a population of people with SMI and SCE,
      testing the association between SCE and prescription medication in an SMI
      population. A sample of 183 participants with SMI was divided into 2 exposure
      groups: high SCE (4 to 7 categories of SCE) and low SCE (0 to 3 categories of
      SCE). Both groups were compared in regard to prescribed dosing of psychotropic
      medications (antipsychotics, mood stabilizers, antidepressants, and
      anxiolytics/hypnotics). Participants who endorsed high SCE received higher doses
      of antipsychotic medications and mood stabilizers than those with low exposure.
      The results demonstrate that people with higher SCE categories received a higher
      dosing of psychotropic medication, specifically antipsychotic medication and mood
      stabilizers. 

PMID- 24678975
TI  - Validation of a brain MRI relaxometry protocol to measure effects of preterm
      birth at a flexible postnatal age.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is a useful tool to study brain
      growth and organization in preterm neonates for clinical and research purposes,
      but its practicality can be limited by time and medical constraints. The aim of
      this study was to determine if MRI relaxometry of the deep nuclei, as opposed to
      white matter, would reflect the influence of gestational age at birth on
      structures essential to motor development, regardless of postnatal age at the
      time of imaging. RESULTS: This was a prospective observational study of infants
      without brain injury on conventional neuroimaging who were cared for in the
      neonatal intensive care unit (NICU) at Vanderbilt. Infants were studied using MRI
      relaxometry within a 2-month window of postmenstrual term age. In 45 infants,
      white matter MRI T1 relaxation times were influenced by both gestational age and
      postnatal age at imaging time (R(2) = 0.19 for gestational age vs. R(2) = 0.34
      adjusting for both gestational age and age at imaging; all p < 0.01). Similar
      results were obtained with T2 relaxation times. In contrast, globus pallidus T1
      reflected gestational age but was minimally affected by postnatal age (R(2) =
      0.50 vs. 0.57, p < 0.001). CONCLUSIONS: The results obtained using this imaging
      protocol are consistent with the slow maturation of the globus pallidus,
      essential to normal development of complex motor programs into adulthood. Globus
      pallidus MRI relaxometry measures the impact of gestational age at birth on brain
      development independent of postnatal age in preterm infants and should prove
      useful for predictive modeling in a flexible time-window around postmenstrual
      term age.

PMID- 24678977
TI  - Nesfatin-1 correlates with hypertension in overweight or obese Han Chinese
      population.
AB  - We investigated blood nesfatin-1 levels in hypertension patients. We found that
      fasting plasma nesfatin-1 levels were significantly higher in hypertension
      patients than in control groups, especially in overweight/obese hypertension
      patients (4.5 +/- 2.1 versus 3.3 +/- 1.1 ng/ml, p < 0.01). Body mass index,
      systolic blood pressure and diastolic blood pressure were indeed positively
      correlated with fasting plasma nesfatin-1 levels (r = 0.234, p < 0.05; r = 0.304,
      p < 0.01; r = 0.251, p < 0.05; r = 0.461, p < 0.01; respectively). Logistic
      regression analysis revealed that the plasma level of nesfatin-1 could be
      independent of risk prediction over standard measures (OR = 1.547, 95% CI: 1.153
      6.273, p = 0.026). Nesfatin-1 has the incremental contribution to hypertension
      risk prediction (IDI: 0.014, p = 0.018; NRI: 0.050, p = 0.043). The plasma
      nesfatin-1 level in hypertension patients with microalbuminuria are significantly
      higher than those without microalbuminuria patients (6.4 +/- 2.1 ng/ml versus 3.9
      +/- 1.8 ng/ml, p < 0.01). Nesfatin-1 might play an important role in obesity
      hypertension, and its increase could be a risk factor for obesity-associated
      hypertension.

PMID- 24678976
TI  - Neonatal exposure to permethrin pesticide causes lifelong fear and spatial
      learning deficits and alters hippocampal morphology of synapses.
AB  - BACKGROUND: During the neurodevelopmental period, the brain is potentially more
      susceptible to environmental exposure to pollutants. The aim was to determine if
      neonatal exposure to permethrin (PERM) pesticide, at a low dosage that does not
      produce signs of obvious abnormalities, could represent a risk for the onset of
      diseases later in the life. METHODS: Neonatal rats (from postnatal day 6 to 21)
      were treated daily by gavage with a dose of PERM (34 mg/kg) close to the no
      observed-adverse-effect level (NOAEL), and hippocampal morphology and function of
      synapses were investigated in adulthood. Fear conditioning, passive avoidance and
      Morris water maze tests were used to assess cognitive skills in rats, whereas
      electron microscopy analysis was used to investigate hippocampal morphological
      changes that occurred in adults. RESULTS: In both contextual and tone fear
      conditioning tests, PERM-treated rats showed a decreased freezing. In the passive
      avoidance test, the consolidation of the inhibitory avoidance was time-limited:
      the memory was not impaired for the first 24 h, whereas the information was not
      retained 72 h following training. The same trend was observed in the spatial
      reference memories acquired by Morris water maze. In PERM-treated rats, electron
      microscopy analysis revealed a decrease of synapses and surface densities in the
      stratum moleculare of CA1, in the inner molecular layer of the dentate gyrus and
      in the mossy fibers of the hippocampal areas together with a decrease of
      perforated synapses in the stratum moleculare of CA1 and in the inner molecular
      layer of the dentate gyrus. CONCLUSIONS: Early-life permethrin exposure imparts
      long-lasting consequences on the hippocampus such as impairment of long-term
      memory storage and synaptic morphology.

PMID- 24678978
TI  - The role of P-glycoprotein in drug resistance in multiple myeloma.
AB  - Multiple myeloma (MM) is a malignant neoplastic cancer of the plasma cells that
      involves the bone marrow. The majority of patients with MM initially respond to
      chemotherapy, but they eventually become resistant to later drug therapy. One of
      the reasons for drug resistance in patients with MM is efflux transporters. P
      glycoprotein (P-gp) is the most studied of the multidrug resistance proteins, and
      is up-regulated in response to many chemotherapeutic drugs. This up-regulation of
      P-gp causes a decrease in the intracellular accumulation of these drugs, limiting
      their therapeutic efficacy. In this review, we focus on the role of P-gp in drugs
      used for patients with MM. P-gp has been found to be an important factor with
      regard to drug resistance in many of the drug classes used in the treatment of MM
      (proteasome inhibitors, anthracyclines, alkylating agents and immunomodulators
      are examples). Thus, our further understanding of its mechanism and inhibitory
      effects will help us decrease drug resistance in patients with MM.

PMID- 24678981
TI  - Origin of ferroelectricity in a family of polar oxides: the Dion-Jacobson phases.
AB  - Recent work on layered perovskites has established the group theoretical
      guidelines under which a combination of octahedral distortions and cation
      ordering can break inversion symmetry, leading to polar structures. The
      microscopic mechanism of this form of ferroelectricity-so-called hybrid-improper
      ferroelectricity-has been elucidated in two families of layered perovskites:
      AA'B2O6 double perovskites and Ruddlesden-Popper phases. In this work, we use
      symmetry principles, crystal chemical models, and first-principles calculations
      to unravel the crystal chemical origin of ferroelectricity in the Dion-Jacobson
      phases, and show that the hybrid improper mechanism can provide a unifying
      explanation for the emergence of polar structures in this family of materials. We
      link trends in the magnitude of the induced polarizations to changes in structure
      and composition and discuss possible phase-transition scenarios. Our results
      suggest that the structures of several Dion-Jacobson phases that have previously
      been characterized as centrosymmetric should be re-examined. Our work adds new
      richness to theories of how polar structures emerge in layered perovskites. 

PMID- 24678980
TI  - Medicinal attributes of Solanum xanthocarpum fruit consumed by several tribal
      communities as food: an in vitro antioxidant, anticancer and anti HIV
      perspective.
AB  - BACKGROUND: Solanum xanthocarpum (Solanaceae) has been used for treatment of many
      infectious and degenerative diseases in traditional medicine. Present study
      reports the medicinal efficacy of S. xanthocarpum fruit as antioxidant,
      anticancer and anti HIV agents. METHODS: Extracts were prepared using Soxhlet
      apparatus and partially characterized by thin layer chromatography (TLC). Total
      flavonoid content was determined spectrophotometrically. Reducing power, DPPH
      radical scavenging activity and lipid peroxidation inhibition assays were used
      for measurement of antioxidant potential. Cytotoxic (SRB assay) and anti-HIV RT
      inhibition (RT assay kit, Roche) activities were determined using ELISA. RESULTS:
      TLC revealed the diversity of phytoconstituents in various sequential extracts of
      S. xanthocarpum fruit. Total flavonoid contents in extracts ranged between 10.22
      162.49 MUg quercetin equivalent/mg. Spectroscopic scanning of water soluble
      phenolics showed maximum absorbance at 250 and 280 nm. Polar extracts displayed
      potent radical scavenging activity (>80%). Several sub-fractions (spots) of
      extracts separated on TLC plates also exhibited powerful radical scavenging
      activity. Considerable reducing power was observed in extracts. Hexane fraction
      provided 55% lipoprotection in rat kidney homogenate. Non-polar extracts
      exhibited appreciable cytotoxic activity (70-91%) against leukemia (THP-1) and
      lung cancer (HOP-62) cell lines. Lower inhibitory activity was observed in
      extracts against HIV Reverse Transcriptase enzyme. CONCLUSION: The study
      demonstrated considerable antioxidant and anticancer activities in S.
      xanthocarpum fruit.

PMID- 24678955
TI  - Darapladib for preventing ischemic events in stable coronary heart disease.
AB  - BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes
      the development of vulnerable atherosclerotic plaques, and elevated plasma levels
      of this enzyme are associated with an increased risk of coronary events.
      Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase
      A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with
      stable coronary heart disease to receive either once-daily darapladib (at a dose
      of 160 mg) or placebo. The primary end point was a composite of cardiovascular
      death, myocardial infarction, or stroke. Secondary end points included the
      components of the primary end point as well as major coronary events (death from
      coronary heart disease, myocardial infarction, or urgent coronary
      revascularization for myocardial ischemia) and total coronary events (death from
      coronary heart disease, myocardial infarction, hospitalization for unstable
      angina, or any coronary revascularization). RESULTS: During a median follow-up
      period of 3.7 years, the primary end point occurred in 769 of 7924 patients
      (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo
      group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI],
      0.85 to 1.03; P=0.20). There were also no significant between-group differences
      in the rates of the individual components of the primary end point or in all
      cause mortality. Darapladib, as compared with placebo, reduced the rate of major
      coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00;
      P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI,
      0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart
      disease, darapladib did not significantly reduce the risk of the primary
      composite end point of cardiovascular death, myocardial infarction, or stroke.
      (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

PMID- 24678982
TI  - Laparoscopic surgery for double gastrointestinal stromal tumor of the stomach: a
      report of two cases.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate
      from interstitial cells of Cajal or their stem cell-like precursors. Generally,
      GISTs have specific c-KIT gene mutations. The incidence of GISTs is estimated to
      be 10 to 20 cases/one million individuals, and GISTs typically affect people over
      50 years of age. The majority of GISTs are solitary. However, multifocal GISTs
      have been observed, especially in children. We report on two unusual adult cases
      of double GISTs that were treated by laparoscopic surgery. The first patient
      presented a polypoid mass of the fundus and a second isolated smaller tumor in
      the posterior wall of the lesser curvature of the stomach. A histopathological
      examination confirmed that both tumors were GISTs and were c-KIT-positive. A
      total laparoscopic gastrectomy was performed. In the second patient, GISTs were
      identified at the level of the fundus and the greater curvature of the stomach. A
      laparoscopic partial sleeve gastrectomy was performed. Both surgeries were
      successful with no complications or relapses at three to five years following
      surgery.

PMID- 24678979
TI  - A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.
AB  - BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase
      subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein
      (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to
      evaluate the safety and efficacy of 52 weeks of treatment with evolocumab.
      METHODS: We stratified patients with hyperlipidemia according to the risk
      categories outlined by the Adult Treatment Panel III of the National Cholesterol
      Education Program. On the basis of this classification, patients were started on
      background lipid-lowering therapy with diet alone or diet plus atorvastatin at a
      dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a
      dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period
      of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter
      (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to
      receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end
      point was the percent change from baseline in LDL cholesterol, as measured by
      means of ultracentrifugation, at week 52. RESULTS: Among the 901 patients
      included in the primary analysis, the overall least-squares mean (+/-SE)
      reduction in LDL cholesterol from baseline in the evolocumab group, taking into
      account the change in the placebo group, was 57.0+/-2.1% (P<0.001). The mean
      reduction was 55.7+/-4.2% among patients who underwent background therapy with
      diet alone, 61.6+/-2.6% among those who received 10 mg of atorvastatin, 56.8+/
      5.3% among those who received 80 mg of atorvastatin, and 48.5+/-5.2% among those
      who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe
      (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced
      levels of apolipoprotein B, non-high-density lipoprotein cholesterol,
      lipoprotein(a), and triglycerides. The most common adverse events were
      nasopharyngitis, upper respiratory tract infection, influenza, and back pain.
      CONCLUSIONS: At 52 weeks, evolocumab added to diet alone, to low-dose
      atorvastatin, or to high-dose atorvastatin with or without ezetimibe
      significantly reduced LDL cholesterol levels in patients with a range of
      cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number,
      NCT01516879.).

PMID- 24678984
TI  - Development and validation of the Experiential Avoidance in Caregiving
      Questionnaire (EACQ).
AB  - OBJECTIVE: Providing care to a relative with dementia is associated with negative
      health consequences. Experiential avoidance has been found to be related to
      caregivers' distress. However, no specific measure of experiential avoidance in
      the caregiving context is available. The aim of this study is to develop and
      present the psychometric properties of the Experiential Avoidance in Caregiving
      Questionnaire (EACQ). METHOD: Face-to-face interviews were conducted with 263
      dementia family caregivers (mean age = 61.37; SD = 14.84; 78.3% female). In
      addition to the EACQ, the Action and Acceptance Questionnaire (AAQ) was used.
      Depression, anxiety, alexithymia, cognitive fusion, dysfunctional thoughts about
      caregiving, and mean arterial pressure were also measured. RESULTS: Using
      principal component analysis, three factors were retained that explained 44.75%
      of the variance. These factors were labeled: (1) Active Avoidant Behaviors; (2)
      Intolerance of Negative Thoughts and Emotions Towards the Relative; and (3)
      Apprehension Concerning Negative Internal Experiences Related to Caregiving.
      Acceptable reliability indexes (Cronbach's alpha) were found for each factor (.63
      for factor 1; .71 for factor 2; and .60 for factor 3) and the total scale (alpha
      = .70). Significant positive associations were found between the global scale and
      anxiety, dysfunctional thoughts, alexithymia and the AAQ. CONCLUSION: The EACQ
      shows acceptable psychometric properties and may be a useful tool for clinical
      assessment and therapeutic work with caregivers.

PMID- 24678985
TI  - ClearedLeavesDB: an online database of cleared plant leaf images.
AB  - BACKGROUND: Leaf vein networks are critical to both the structure and function of
      leaves. A growing body of recent work has linked leaf vein network structure to
      the physiology, ecology and evolution of land plants. In the process, multiple
      institutions and individual researchers have assembled collections of cleared
      leaf specimens in which vascular bundles (veins) are rendered visible. In an
      effort to facilitate analysis and digitally preserve these specimens, high
      resolution images are usually created, either of entire leaves or of magnified
      leaf subsections. In a few cases, collections of digital images of cleared leaves
      are available for use online. However, these collections do not share a common
      platform nor is there a means to digitally archive cleared leaf images held by
      individual researchers (in addition to those held by institutions). Hence, there
      is a growing need for a digital archive that enables online viewing, sharing and
      disseminating of cleared leaf image collections held by both institutions and
      individual researchers. DESCRIPTION: The Cleared Leaf Image Database
      (ClearedLeavesDB), is an online web-based resource for a community of researchers
      to contribute, access and share cleared leaf images. ClearedLeavesDB leverages
      resources of large-scale, curated collections while enabling the aggregation of
      small-scale collections within the same online platform. ClearedLeavesDB is built
      on Drupal, an open source content management platform. It allows plant biologists
      to store leaf images online with corresponding meta-data, share image collections
      with a user community and discuss images and collections via a common forum. We
      provide tools to upload processed images and results to the database via a web
      services client application that can be downloaded from the database.
      CONCLUSIONS: We developed ClearedLeavesDB, a database focusing on cleared leaf
      images that combines interactions between users and data via an intuitive web
      interface. The web interface allows storage of large collections and integrates
      with leaf image analysis applications via an open application programming
      interface (API). The open API allows uploading of processed images and other
      trait data to the database, further enabling distribution and documentation of
      analyzed data within the community. The initial database is seeded with nearly
      19,000 cleared leaf images representing over 40 GB of image data. Extensible
      storage and growth of the database is ensured by using the data storage resources
      of the iPlant Discovery Environment. ClearedLeavesDB can be accessed at
      http://clearedleavesdb.org.

PMID- 24678986
TI  - Behind the reactivity of lactones: a computational and spectroscopic study of
      phenol.gamma-butyrolactone.
AB  - In this work, the intermolecular interaction between phenol and gamma
      butyrolactone (GBL) has been studied by a combination of spectroscopic and
      computational techniques. The electronic and vibrational transitions of phenol .
      GBL were measured in a supersonic jet expansion by resonant two-photon ionization
      (R2PI) and ion dip IR (IDIR) spectroscopy. The results obtained were compared
      with calculations carried out with both M06-2X and MP2 molecular orbital methods
      in order to characterize the intermolecular interactions. The singly detected
      conformer is stabilized by a relatively strong hydrogen bond in which phenol acts
      as a proton donor to the carbonyl group of GBL. The phenol . GBL2 cluster has
      also been studied, finding up to three populated conformers. Nevertheless, in the
      three species, the main interaction between the phenolic hydroxyl group and the
      GBL's carbonyl group remains similar to that of phenol . GBL. Furthermore, the C
      ? O . . . H interaction is reinforced.

PMID- 24678983
TI  - Alignment of patient and primary care practice member perspectives of chronic
      illness care: a cross-sectional analysis.
AB  - BACKGROUND: Little is known as to whether primary care teams' perceptions of how
      well they have implemented the Chronic Care Model (CCM) corresponds with their
      patients' own experience of chronic illness care. We examined the extent to which
      practice members' perceptions of how well they organized to deliver care
      consistent with the CCM were associated with their patients' perceptions of the
      chronic illness care they have received. METHODS: Analysis of baseline measures
      from a cluster randomized controlled trial testing a practice facilitation
      intervention to implement the CCM in small, community-based primary care
      practices. All practice "members" (i.e., physician providers, non-physician
      providers, and staff) completed the Assessment of Chronic Illness Care (ACIC)
      survey and adult patients with 1 or more chronic illnesses completed the Patient
      Assessment of Chronic Illness Care (PACIC) questionnaire. RESULTS: Two sets of
      hierarchical linear regression models accounting for nesting of practice members
      (N = 283) and patients (N = 1,769) within 39 practices assessed the association
      between practice member perspectives of CCM implementation (ACIC scores) and
      patients' perspectives of CCM (PACIC). ACIC summary score was not significantly
      associated with PACIC summary score or most of PACIC subscale scores, but four of
      the ACIC subscales [Self-management Support (p < 0.05); Community Linkages (p <
      0.02), Delivery System Design (p < 0.02), and Organizational Support (p < 0.02)]
      were consistently associated with PACIC summary score and the majority of PACIC
      subscale scores after controlling for patient characteristics. The magnitude of
      the coefficients, however, indicates that the level of association is weak.
      CONCLUSIONS: The ACIC and PACIC scales appear to provide complementary and
      relatively unique assessments of how well clinical services are aligned with the
      CCM. Our findings underscore the importance of assessing both patient and
      practice member perspectives when evaluating quality of chronic illness care.
      TRIAL REGISTRATION: NCT00482768.

PMID- 24678987
TI  - Myopericarditis complicated by pulmonary embolism in an immunocompetent patient
      with acute cytomegalovirus infection: a case report.
AB  - BACKGROUND: Primary acute cytomegalovirus infection in immunocompetent patients
      is common worldwide. Infection is most often asymptomatic or occurs sub
      clinically with a self-limited mononucleosis-like syndrome. More rarely, the
      infection may lead to severe organ complications with pneumonia, myocarditis,
      pericarditis, colitis and hemolytic anemia. Recent cases of cytomegalovirus
      associated thrombosis have also been reported sporadically in the medical
      literature. CASE PRESENTATION: We report here a case of simultaneous
      myopericarditis and pulmonary embolism in a 30-year-old man with no medical
      history. The patient was not immunocompromised. We discuss the possible role of
      acute cytomegalovirus infection in the induction of vascular damage and review
      relevant cases in the literature. CONCLUSION: Thrombosis in patients with acute
      cytomegalovirus infection may be more frequent than is generally thought.
      Physicians need to be aware of the possible association between acute
      cytomegalovirus and thrombosis in immunocompetent patients, especially in the
      presence of severe systemic infection, as our case illustrates.

PMID- 24678988
TI  - Umbilical cord shortening: quantification postdelivery and postfixation.
AB  - The length of the umbilical cord is an important data item, and little is known
      about the effects of time and fixation on measurement. Such a change has
      implications for the diagnosis of a long and short cord. This study was conducted
      to examine the effects of time and formalin fixation on cord length in a routine
      practice setting. We measured 90 cords from singleton term pregnancies within 5
      minutes of delivery, again in the fresh state at 1 to 2 hours, and again after 24
      to 48 hours of formalin fixation. The mean cord length was 536.7 mm at delivery.
      Mean cord shortening was 17.6 mm (3% reduction in length) between delivery and
      measurement at 1 to 2 hours, and 62.2 mm (12% reduction) between delivery and
      measurement after 24 to 48 hours fixation. Both values were statistically
      significant (P < 0.001). Studies on cord length should include data on time of
      measurement and fixation status.

PMID- 24678990
TI  - Polyaniline and polypyrrole pseudocapacitor electrodes with excellent cycling
      stability.
AB  - Conducting polymers such as polyaniline and polypyrrole have been widely used as
      pseudocapacitive electrode materials for supercapacitors. However, their
      structural instability resulting from repeated volumetric swelling and shrinking
      during charge/discharge process has been a major hurdle for their practical
      applications. This work demonstrates a simple and general strategy to
      substantially enhance the cycling stability of conductive polymer electrodes by
      deposition of a thin carbonaceous shell onto their surface. Significantly,
      carbonaceous shell-coated polyaniline and polypyrrole electrodes achieved
      remarkable capacitance retentions of ~95 and ~85% after 10,000 cycles. Electron
      microscopy studies revealed that the presence of ~5 nm thick carbonaceous shell
      can effective prevent the structural breakdown of polymer electrodes during
      charge/discharge process. Importantly, the polymer electrodes with a ~5 nm thick
      carbonaceous shell exhibited comparable specific capacitance and pseudocapacitive
      behavior as the bare polymer electrodes. We anticipate that the same strategy can
      be applied for stabilizing other polymer electrode materials. The capability of
      fabricating stable polymer electrodes could open up new opportunities for
      pseudocapacitive devices.

PMID- 24678989
TI  - Timing and intensity of exposure to interferon-gamma critically determines the
      function of monocyte-derived dendritic cells.
AB  - A growing body of evidence suggests that inflammatory cytokines have a dualistic
      role in immunity. In this study, we sought to determine the direct effects of
      interferon-gamma (IFN-gamma) on the differentiation and maturation of human
      peripheral blood monocyte-derived dendritic cells (moDC). Here, we report that
      following differentiation of monocytes into moDC with granulocyte-macrophage
      colony-stimulating factor and interleukin-4, IFN-gamma induces moDC maturation
      and up-regulates the co-stimulatory markers CD80/CD86/CD95 and MHC Class I,
      enabling moDC to effectively generate antigen-specific CD4(+) and CD8(+) T-cell
      responses for multiple viral and tumour antigens. Early exposure of monocytes to
      high concentrations of IFN-gamma during differentiation promotes the formation of
      macrophages. However, under low concentrations of IFN-gamma, monocytes continue
      to differentiate into dendritic cells possessing a unique gene-expression
      profile, resulting in impairments in subsequent maturation by IFN-gamma or
      lipopolysaccharide and an inability to generate effective antigen-specific CD4(+)
      and CD8(+) T-cell responses. These findings demonstrate that IFN-gamma imparts
      differential programmes on moDC that shape the antigen-specific T-cell responses
      they induce. Timing and intensity of exposure to IFN-gamma can therefore
      determine the functional capacity of moDC. 

PMID- 24678991
TI  - Development and practical application of petroleum and dispersant interspecies
      correlation models for aquatic species.
AB  - Assessing the acute toxicity of oil has generally relied on existing
      toxicological data for a relatively few standard test species, which has limited
      the ability to estimate the impacts of spilled oil on aquatic communities.
      Interspecies correlation estimation (ICE) models were developed for petroleum and
      dispersant products to facilitate the prediction of toxicity values to a broader
      range of species and to better understand taxonomic differences in species
      sensitivity. ICE models are log linear regressions that can be used to estimate
      toxicity to a diversity of taxa based on the known toxicity value for a surrogate
      tested species. ICE models have only previously been developed for nonpetroleum
      chemicals. Petroleum and dispersant ICE models were statistically significant for
      93 and 16 unique surrogate-predicted species pairs, respectively. These models
      had adjusted coefficient of determinations (adj-R(2)), square errors (MSE) and
      positive slope ranging from 0.29 to 0.99, 0.0002 to 0.311, and 0.187 to 2.665,
      respectively. Based on model cross-validation, predicted toxicity values for most
      ICE models (>90%) were within 5-fold of the measured values, with no influence of
      taxonomic relatedness on prediction accuracy. A comparison between hazard
      concentrations (HC) derived from empirical and ICE-based species sensitivity
      distributions (SSDs) showed that HC values were within the same order of
      magnitude of each other. These results show that ICE-based SSDs provide a
      statistically valid approach to estimating toxicity to a range of petroleum and
      dispersant products with applicability to oil spill assessment. 

PMID- 24678992
TI  - Assessment of postural stabilization in three task oriented movements in people
      with multiple sclerosis.
AB  - PURPOSE: In accordance with the Task Oriented Approach, clinicians need
      assessment procedures providing information on the execution of multiple tasks.
      Instrumented task assessment can add information regarding sensory-motor
      strategies, difficult to assess purely by clinical observation. It has been shown
      that People with Multiple Sclerosis (PwMS) have difficulties in maintaining
      upright balance, but little is known about their ability to achieve a stable
      posture after the execution of tasks related to activities of daily living. The
      aim of the present study was to assess postural stabilization in a population of
      PwMS. METHODS: Twenty Healthy Subjects (HS) and twenty PwMS were assessed in
      three tasks leading to a quiet erect posture: sit-to-stand, taking a step
      forward, bending forward. Antero-posterior ground reaction force was measured by
      a force platform and interpolated by a model providing information on the initial
      instability after task execution (Transitional_Sway), the time required to
      dissipate this initial instability (Stabilization_Time), and their stability in
      quiet upright posture (Static_Sway). RESULTS: PwMS had statistically significant
      altered performance in comparison to HS: their instability after task execution
      (Transitional_Sway) was higher in bending and sit-to-stand (p < 0.05), their
      stabilization time (Stabilization_Time) was longer in bending and step forward (p
      < 0.05). Static_Sway was higher in all tasks (p < 0.05) indicating imbalance also
      in quiet upright posture.

PMID- 24678993
TI  - Validity of the single limb heel raise test to predict lower extremity
      disablement in patients with sporadic inclusion body myositis.
AB  - PURPOSE: To determine the validity of the single limb heel raise (SLHR) test as a
      potential screening tool to detect lower extremity disability in patients with
      sporadic inclusion body myositis (sIBM). METHODS: We compared gait speed and fall
      history between subjects with sIBM who either could complete one SLHR (SLHR
      group) or could not complete one SLHR. Discriminative validity was established by
      comparing between group differences in functional measures based on group
      assignment. Receiver operating characteristics curve analysis was used to
      determine the predictive validity of completing one repetition on the SLHR test.
      Spearman correlations were used to determine the association between gait
      kinematics and number of repetitions achieved on the SLHR test. RESULTS: Forty
      three subjects (13 females) were studied. The SLHR group (n = 21) showed
      significantly greater gait speed (p < 0.001) and decreased gait aid use (p <
      0.05) compared to the no SLHR group (n = 22). SLHR cut scores of 1, 20, and 22
      repetitions maximized positive likelihood ratios (+LR) for the ability to walk at
      54.9 (+LR. 2.2), 63.2 (+LR. 9.5), and 73.1 m/min (+LR. 5.0), respectively.
      CONCLUSION: The SLHR test demonstrates adequate discriminative and predictive
      validity as a screening tool for lower extremity disablement in patients with
      sIBM. Implications for Rehabilitation The SLHR test has adequate reliability and
      validity to screen for the presence of lower extremity disablement in patients
      with sIBM. Results of this rapid field test may be used to guide the need for
      rehabilitation services to mitigate the effects of slow gait speeds in patients
      with sIBM.

PMID- 24678994
TI  - Chemical constituents from the ethanol extract of Viburnum ternatum.
AB  - Phytochemical investigation of the 70% ethanol extract from Viburnum ternatum
      resulted in the isolation of three new compounds, vibsanol-9'-al (1), 4-methoxy
      vibsanol (2), and 5,7-dihydroxy-4'-methoxyflavanone(8 -> 3')-5,7-dihydroxy-4'
      methoxyflavone (4), together with a known compound vibsanol (3). Their structures
      were determined on the basis of spectroscopic analyses, including 1D and 2D NMR
      (COSY, HMQC, HMBC, and NOESY) and HR-ESI-MS analyses. 

PMID- 24678995
TI  - Decreased expression of the Nkx2.8 gene correlates with tumor progression and a
      poor prognosis in HCC cancer.
AB  - BACKGROUND: Nkx2.8 (Nk2 homeobox 8) is a novel NK-2 gene family member that has
      been implicated in the progression of human cancer. Its role in the progression
      of HCC remains unknown. In this study, we investigated the expression levels and
      prognostic value of Nkx2.8 in hepatocellular carcinoma. METHODS: The expression
      of Nkx2.8 was determined by real-time quantitative RT-PCR (qRT-PCR) and
      immunochemistry in paired cancerous and non-cancerous tissues of 48 patients with
      HCC. The relationships between the Nkx2.8 expression levels, the
      clinicopathological characteristics and patient survival were analyzed. The
      effects of Nkx2.8 overexpression on cellular proliferation ability, including MTT
      and colony formation assays, were investigated. RESULTS: Nkx2.8 expression was
      significantly downregulated in HCC cancer tissues compared with adjacent non
      cancerous tissues. Further immunohistochemical analysis showed low expression of
      Nkx2.8 in HCC cancer tissues, and the clinicopathological analysis showed that
      the Nkx2.8 mRNA and protein expression levels were significantly correlated with
      the TNM stage (p = 0.032; p = 0.026, respectively). Kaplan-Meier survival curves
      revealed that lower Nkx2.8 expression was associated with a poor overall survival
      in HCC patients (P = 0.00172). The overexpression of Nkx2.8 in HCC cell lines
      inhibits cell proliferation and colony formation. CONCLUSIONS: Our data indicated
      that Nkx2.8 plays important roles in the development and progression of HCC and
      might be a valuable prognostic biomarker and potential therapeutic target for
      HCC.

PMID- 24678996
TI  - Role of surface structure on Li-ion energy storage capacity of two-dimensional
      transition-metal carbides.
AB  - A combination of density functional theory (DFT) calculations and experiments is
      used to shed light on the relation between surface structure and Li-ion storage
      capacities of the following functionalized two-dimensional (2D) transition-metal
      carbides or MXenes: Sc2C, Ti2C, Ti3C2, V2C, Cr2C, and Nb2C. The Li-ion storage
      capacities are found to strongly depend on the nature of the surface functional
      groups, with O groups exhibiting the highest theoretical Li-ion storage
      capacities. MXene surfaces can be initially covered with OH groups, removable by
      high-temperature treatment or by reactions in the first lithiation cycle. This
      was verified by annealing f-Nb2C and f-Ti3C2 at 673 and 773 K in vacuum for 40 h
      and in situ X-ray adsorption spectroscopy (XAS) and Li capacity measurements for
      the first lithiation/delithiation cycle of f-Ti3C2. The high-temperature removal
      of water and OH was confirmed using X-ray diffraction and inelastic neutron
      scattering. The voltage profile and X-ray adsorption near edge structure of f
      Ti3C2 revealed surface reactions in the first lithiation cycle. Moreover,
      lithiated oxygen terminated MXenes surfaces are able to adsorb additional Li
      beyond a monolayer, providing a mechanism to substantially increase capacity, as
      observed mainly in delaminated MXenes and confirmed by DFT calculations and XAS.
      The calculated Li diffusion barriers are low, indicative of the measured high
      rate performance. We predict the not yet synthesized Cr2C to possess high Li
      capacity due to the low activation energy of water formation at high temperature,
      while the not yet synthesized Sc2C is predicted to potentially display low Li
      capacity due to higher reaction barriers for OH removal. 

PMID- 24678997
TI  - 11p15 DNA-methylation analysis in monozygotic twins with discordant intrauterine
      development due to severe twin-to-twin transfusion syndrome.
AB  - BACKGROUND: Prenatal growth restriction and low birth weight have been linked to
      long-term alterations of health, presumably via adaptive modifications of the
      epigenome. Recent studies indicate a plasticity of the 11p15 epigenotype in
      response to environmental changes during early stages of human development. STUDY
      DESIGN: We analyzed methylation levels at different 11p15 loci in 20 growth
      discordant monozygotic twin pairs. Intrauterine development was discordant due to
      severe twin-to-twin transfusion syndrome (TTTS), which was treated by fetoscopic
      laser coagulation of communicating vessels before 25 weeks of gestation.
      Methylation levels at age 4 were determined in blood and buccal cell-derived DNA
      by the single nucleotide primer extension reaction ion pair reverse-phase high
      performance liquid chromatography (SNuPE IP RP HPLC) assay. Methylation at LINE-1
      repeats was analyzed as an estimate of global methylation. RESULTS: In general,
      variance of locus-specific methylation levels appeared to be higher in buccal
      cell- as compared to blood cell-derived DNA samples. Paired analyses within the
      twin pairs revealed significant differences at only one CpG site (IGF2 dmr0 SN3
      (blood), +1.9% in donors; P = 0.013). When plotting the twin pair-discordance in
      birth weight against the degree of discordance in site-specific methylation at
      age 4, only a few CpGs were found to interact (one CpG site each at IGF2dmr0 in
      blood/saliva DNA, one CpG at LINE-1 repeats in saliva DNA), with 26 to 36% of the
      intra-twin pair divergence at these sites explained by prenatal growth
      discordance. However, across the entire cohort of 40 children, site-specific
      methylation did not correlate with SD-scores for weight or length at birth.
      Insulin-like growth factor-II serum concentrations showed significant within-twin
      pair correlations at birth (R = 0.57) and at age 4 (R = 0.79), but did not differ
      between donors and recipients. They also did not correlate with the analyzed
      11p15 methylation parameters. CONCLUSION: In a cohort of 20 growth-discordant
      monozygotic twin pairs, severe alteration in placental blood supply due to TTTS
      appears to leave only weak, if any, epigenetic marks at the analyzed CpG sites at
      11p15.

PMID- 24678998
TI  - Visit-to-visit variability in systolic blood pressure: correlated with the
      changes of arterial stiffness and myocardial perfusion in on-treated hypertensive
      patients.
AB  - BACKGROUND: Visit-to-visit variability in blood pressure (BP) was demonstrated to
      correlate with cardiovascular events independent of mean BP. The goal of the
      present study was to investigate the correlation of visit-to-visit BP variability
      with artery stiffness and myocardial perfusion in on-treated hypertensive
      patients. METHODS: BP was measured in 271 hypertensive patients at every visit
      over the course of the antihypertensive treatment, and the standard deviation
      (SD), coefficient of variation (CV), maximum, and minimum in serial BP were
      calculated. Non-invasive pulse wave analysis was performed in all patients.
      RESULTS: Compared with baseline, carotid-femoral pulse wave velocity (cfPWV),
      aortic augmentation index (Aix) and Aix adjusted to a "standard heart rate" of 75
      beats/min (Aix@HR75) were markedly declined, and sub-endocardial viability ratio
      (SEVR) was obviously increased in each group (p < 0.001). The changes of cfPWV,
      SEVR, Aix and Aix@HR75 in patients with lower SD of systolic blood pressure (SBP)
      were significantly greater than those in patients with higher SD of SBP. And the
      changes were statistically correlated with both SD and CV of serial SBP during
      follow-up, even after adjusted for mean SBP and mean diastolic blood pressure
      (DBP). CONCLUSION: Visit-to-visit SBP variability is independently correlated
      with changes of artery stiffness and myocardial perfusion in on-treated
      hypertensive patients.

PMID- 24678999
TI  - Survival with cardiac-resynchronization therapy in mild heart failure.
AB  - BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial with
      Cardiac Resynchronization Therapy (MADIT-CRT) showed that early intervention with
      cardiac-resynchronization therapy with a defibrillator (CRT-D) in patients with
      an electrocardiographic pattern showing left bundle-branch block was associated
      with a significant reduction in heart-failure events over a median follow-up of
      2.4 years, as compared with defibrillator therapy alone. METHODS: We evaluated
      the effect of CRT-D on long-term survival in the MADIT-CRT population. Post-trial
      follow-up over a median period of 5.6 years was assessed among all 1691 surviving
      patients (phase 1) and subsequently among 854 patients who were enrolled in post
      trial registries (phase 2). All reported analyses were performed on an intention
      to-treat basis. RESULTS: At 7 years of follow-up after initial enrollment, the
      cumulative rate of death from any cause among patients with left bundle-branch
      block was 18% among patients randomly assigned to CRT-D, as compared with 29%
      among those randomly assigned to defibrillator therapy alone (adjusted hazard
      ratio in the CRT-D group, 0.59; 95% confidence interval [CI], 0.43 to 0.80;
      P<0.001). The long-term survival benefit of CRT-D in patients with left bundle
      branch block did not differ significantly according to sex, cause of
      cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any
      clinical benefit and possibly with harm in patients without left bundle-branch
      block (adjusted hazard ratio for death from any cause, 1.57; 95% CI, 1.03 to
      2.39; P=0.04; P<0.001 for interaction of treatment with QRS morphologic
      findings). CONCLUSIONS: Our findings indicate that in patients with mild heart
      failure symptoms, left ventricular dysfunction, and left bundle-branch block,
      early intervention with CRT-D was associated with a significant long-term
      survival benefit. (Funded by Boston Scientific; ClinicalTrials.gov numbers,
      NCT00180271, NCT01294449, and NCT02060110.).

PMID- 24679000
TI  - Left bundle-branch block myopathy in heart failure.

PMID- 24679001
TI  - Expressions of TRPM6 and TRPM7 and histopathological evaluation of tissues in
      ischemia reperfusion performed rats.
AB  - There is very little work on the expression of TRPM6/7 in ischemia reperfusion
      models. In previous studies, after ischemia, reperfusion had been kept limited to
      24 h, yet in our study, expressions of these channels were elucidated after its
      modification to 48 h to establish what kind of changes renal tissues undergo. For
      the current study, 20 Wistar albino rats were divided into two groups equally.
      Group I: control group, Group II = I/R group (60 min ischemia + 48 h
      reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a
      reference in order to eliminate genetic differences. The left renal artery (I/R
      generated part) of I/R area was removed from all rats in the second group.
      Likewise, normal tissues of right renal artery were removed from all rats.
      Histopathologic scoring of the tissue samples were achieved semi-quantitatively
      according to normal tissue composition. Consequently, both TRPM6 and TRPM7
      expression levels were decreased in all groups according to control groups, yet
      results were not counted as significant (p > 0.05). Additionally, correlation
      analysis confirmed these results. Also, I/R performed kidneys had more tissue
      damage compared to control group. To conclude, our study results suggest that
      TRPM6/7 expressions may be increased and after 48 h of reperfusion expression
      levels of these two stored to normal levels. At the same time, damages have
      occurred in renal tissues after ischemia. These damages were considered to be
      resulted from the oxidative effects as previously reported.

PMID- 24679002
TI  - Primary oesophageal melanoma - a case report.
AB  - Primary upper gastrointestinal tract melanoma is a rare but well recognised
      entity, with a poor prognosis because of delay in diagnosis. Furthermore, it may
      be difficult to determine whether a gastrointestinal melanoma represents a
      metastasis or a primary tumour. We report a 67-year-old man with a primary
      oesophageal melanoma, treated with surgical resection, who remains disease-free
      two years post resection. 

PMID- 24679003
TI  - Determinants of geriatric patients' quality of life after stroke rehabilitation.
AB  - OBJECTIVES: Geriatric patients' physical disabilities, dependency on care, and
      possible psychological ill-being may negatively affect both the patient's quality
      of life and the informal caregiver burden. Focusing on this interrelationship
      which can be particularly prominent in geriatric patients with stroke, the
      objective of this study was to identify determinants of patients' quality of life
      and informal caregiver burden. METHOD: This is a prospective, multicentre, cohort
      study. Data were collected in 84 geriatric home-dwelling patients with stroke
      three months after their rehabilitation period in skilled nursing facilities
      (SNFs). We assessed patients' quality of life, depressive complaints,
      neuropsychiatric symptoms, balance, (instrumental) activities of daily living,
      and informal caregiver burden. Linear regression models were constructed to study
      the association between the variables. RESULTS: For several domains, high quality
      of life of these geriatric patients was associated with high functional
      independence, less neuropsychiatric symptoms, and less depressive complaints.
      Informal caregiver burden was not associated with patients' quality of life, but
      patients' neuropsychiatric symptoms were a significant determinant of high
      informal caregiver burden. CONCLUSION: The presence of neuropsychiatric symptoms
      (more specifically depressive complaints) negatively affects the quality of life
      of geriatric patients. Their neuropsychiatric symptoms also affect caregiver
      burden. Health care professionals in SNFs can play an important role in providing
      the necessary psychosocial support and aftercare.

PMID- 24679005
TI  - Effect of molecular architecture on single polymer adhesion.
AB  - Several applications require strong noncovalent adhesion of polymers to
      substrates. Graft and branched polymers have proven superior to linear polymers,
      but the molecular mechanism is still unclear. Here, this question is addressed on
      the single molecule level with an atomic force microscopy (AFM) based method. It
      is determined how the presence of side chains and their molecular architecture
      influence the adhesion and the mobility of polymers on solid substrates.
      Surprisingly, the adhesion of mobile polymers cannot significantly be improved by
      side chains or their architecture. Only for immobile polymers a significantly
      higher maximum rupture force for graft, bottle-brush, and branched polymers
      compared to linear chains is measured. Our results suggest that a combination of
      polymer architecture and strong molecular bonds is necessary to increase the
      polymer-surface contact area. An increased contact area together with intrachain
      cohesion (e.g., by entanglements) leads to improved polymer adhesion. These
      findings may prove useful for the design of stable polymer coatings. 

PMID- 24679004
TI  - Comparing local perspectives on women's health with statistics on maternal
      mortality: an ethnobotanical study in Benin and Gabon.
AB  - BACKGROUND: According to the World Health Organization (WHO), reproductive health
      problems are the leading cause of morbidity and mortality for women in Africa. In
      spite of this scenario and the importance of plants in African health care,
      limited research has been conducted linking maternal health and plant-based
      medicine. The objective of our research was to examine how closely Beninese and
      Gabonese women's health perspectives, medicinal plant knowledge, and plant use
      practices reflect the statistical causes of maternal mortality. METHODS: In Benin
      (2011) and Gabon (2012), we conducted 87 ethnobotanical questionnaires with the
      corresponding collection of 800 botanical specimens. We used free-listing
      analysis, citation frequency and species counts to determine women's top health
      concerns. We also interviewed 18 biomedical healthcare providers in national
      hospitals and local clinics. RESULTS: Informants' perceptions of the main causes
      of maternal suffering included malaria, infertility, and menstruation and
      pregnancy concerns. Women were knowledgeable on plants to treat the top causes of
      maternal morbidity, but knew more plants for conditions such as anemia,
      infertility, breast milk production, and the maintenance of menstruation and
      pregnancy. The biomedical staff recognized the role of traditional medicine in
      their patients' lives and expressed concern for herbal remedies to facilitate
      birth, but were restricted by national policies on advising on medicinal plant
      use. CONCLUSIONS: Plants serve as an entry point to understanding Beninese and
      Gabonese women's perceptions of common health concerns and local health
      management strategies. Plant use practices in both countries did not closely
      parallel the top statistical causes of maternal mortality, but highlighted key
      issues such as menstruation and infertility as salient health concerns for women.
      More research is needed on the role of plants in women's gynecological
      healthcare.

PMID- 24679006
TI  - TP53 mutations are frequent events in double-hit B-cell lymphomas with MYC and
      BCL2 but not MYC and BCL6 translocations.
AB  - Double-hit lymphomas (DHL) with MYC and either BCL2 or BCL6 rearrangements are
      rare neoplasms with an aggressive clinical presentation and grim prognosis.
      Moreover, molecular characterization of DHL remains insufficient, and especially
      the role of TP53 pathway disruption is unknown. We employed a next-generation
      sequencing approach to investigate the mutational status of TP53 in DHL and
      correlated genomic data with immunohistochemical reactivity for p53. We
      identified TP53 mutations in MYC+/BCL2+ lymphomas at a frequency intermediate
      between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Remarkably,
      TP53 mutations were particularly scarce in MYC+/BCL6+ lymphomas. Our findings
      indicate a significant difference between these two types of DHL at a molecular
      level with pathogenetic implications, as arguably, TP53 mutations inhibiting p53
      mediated promotion of apoptosis pose a synergistic advantage in clonal evolution
      of cells with malignantly enforced overexpression of BCL2. Immunohistochemical
      staining appears to be a sensitive surrogate of TP53 mutation status with
      moderate specificity.

PMID- 24679007
TI  - A study of gemcitabine, l-asparaginase, ifosfamide, dexamethasone and etoposide
      chemotherapy for newly diagnosed stage IV, relapsed or refractory extranodal
      natural killer/T-cell lymphoma, nasal type.

PMID- 24679008
TI  - A phase I/II study of the pan Bcl-2 inhibitor obatoclax mesylate plus bortezomib
      for relapsed or refractory mantle cell lymphoma.
AB  - Obatoclax, a BH3 mimetic inhibitor of anti-apoptotic Bcl-2 proteins, demonstrates
      synergy with bortezomib in preclinical models of mantle cell lymphoma (MCL). This
      phase I/II study assessed obatoclax plus bortezomib in patients with
      relapsed/refractory MCL. Twenty-three patients received obatoclax 30 or 45 mg
      plus bortezomib 1.0 or 1.3 mg/m(2), administered intravenously on days 1, 4, 8
      and 11 of a 21-day cycle. In phase I, the combination was feasible at all doses.
      Obatoclax 45 mg plus bortezomib 1.3 mg/m(2) was selected for phase II study.
      Common adverse events were somnolence (87%), fatigue (61%) and euphoric mood
      (57%), all primarily grade 1/2. Grade 3/4 events included thrombocytopenia (21%),
      anemia (13%) and fatigue (13%). Objective responses occurred in 4/13 (31%)
      evaluable patients (three complete and one partial response). Six patients (46%)
      had stable disease lasting >= 8 weeks. Obatoclax plus bortezomib was feasible,
      but the synergy demonstrated in preclinical models was not confirmed.

PMID- 24679009
TI  - High success rate of repeat colonoscopy with standard endoscopes in patients
      referred for prior incomplete colonoscopy.
AB  - BACKGROUND: In patients with incomplete colonoscopy, cecal intubation is
      sometimes unsuccessful due to a redundant or tortuous colon. Repeat colonoscopy
      may be successful with the use of alternate endoscopes or careful attention to
      technique but limited outcomes data is available. The aim of this study was to
      describe the technique, success rate and outcomes of consecutive patients
      referred for previous incomplete colonoscopy. METHODS: We conducted a
      retrospective chart review of incomplete colonoscopy procedures in patients age
      18-90 at an academic teaching hospital referred to an endoscopist specializing in
      difficult colonoscopy. RESULTS: Cecal intubation was successful in 96 of 100
      repeat colonoscopies and 83 procedures were completed with a standard endoscope
      (adult, pediatric, or gastroscope). The adenoma detection rate was 28% for
      successful repeat colonoscopies; a majority of these patients had no adenomas
      identified on incomplete exam. In 69.4% of cases, an endoscope was used to
      successfully complete colonoscopy that was not used in the incomplete
      colonoscopy. The median insertion time was significantly less for the complete
      colonoscopy (10.6 min) compared to the incomplete colonoscopy (18.8 min, P =
      0.004). CONCLUSIONS: Repeat colonoscopy has a high success rate and identified a
      significant number of new adenomas. Use of all available endoscopes should be
      considered prior to procedure termination in patients with a tortuous colon.
      Repeat colonoscopy can often be accomplished using a standard endoscope and is
      not attributed to increased endoscope insertion time.

PMID- 24679010
TI  - A personal view of nutrition in Spain.
AB  - This paper stems from the special lecture given by the author at 20th
      International Congress of Nutrition, held from 16 to 20 September 2013 in Granada
      (Spain), following for his appointment as "Living Legend" of the International
      Union of nutritional sciences (IUNS), in recognition of his outstanding
      contribution to research and development in nutritional science. The development
      of nutrition in Spain from the 1960s to the present, which the author had the
      opportunity to experience first hand, is described. The contribution covers an
      extensive period in the history of this science, and highlights the advances made
      in our knowledge of nutrition and several of the misunderstandings that existed
      and still exist in this science: 1) The Anglo-Saxon dietary pattern and the high
      incidence of death from myocardial infarction, and the subsequent recognition of
      the Mediterranean diet as a model of a varied and balanced and healthy eating. 2)
      The relationship between cardiovascular disease and the consumption of oily fish.
      Since the discovery of the syn - thesis of prostaglandins makes it clear that
      fish fat is heart-healthy. 3) The epidemic of prosperity, overweight and obesity
      and the appearance of miracle diets. However, there are not miracles, the only
      solution being a healthy lifestyle and a balanced hypocaloric diet. 4) In the
      field of nutrition, diet and health, the harmful effect of: "In my opinion", a
      single allusion that undermines all science. The author also acknowledges all the
      researchers whose efforts, tenacity and enthusiasm have contributed to the
      advances made in nutrition science in Spain. 

PMID- 24679011
TI  - [Intake of trans fats; situation in Spain].
AB  - Current nutritional recommendations include decreasing the intake of trans fatty
      acids (TFA), since there exists sufficient scientific evidence of its influence
      to cardiovascular disease. During the last decades, in many European countries
      the TFA intake has considerably decreased through the established legislation and
      changes in the technological processes developed by the food industry. In Spain,
      just 2.1 g/day, a 0.7% of the daily energy intake comes from TFA, a lower value
      than the recommended maximum (<1%), according to data from TRANSFAIR study. The
      TFA content of processed products such as margarines, factory-baked goods and
      etc, has declined over recent years and is less than 1% in more than 90% of all
      these products in Spain. However, it is necessary to develop and implement
      regulations, governing the TFA content in the products sold in our country, in
      which there should be the requirement to include this information in the label
      too.

PMID- 24679012
TI  - [Neurological changes related to malnutrition during the spanish civil war (1936
      1939)].
AB  - In this lecture, given at the International Conferences on Neuroscience, in
      Quito, May 31st-June 1st of 2013, the topic of famine situations during the
      Spanish Civil War, 1936-1939, was approached. Madrid, the capital of Spain, was
      under food, water and milk rationing during that period. This situation led to
      conditions that showed the relationships between the nervous system and
      nutrition. The Madrilenian population was submitted to a real experiment of
      hyponutrition, similar to the one that may be reproduced at the laboratory. At
      the end of the war, the National Direction on Health and the Institute of Medical
      Investigations, with the collaboration of the Rockefeller Foundation, carried out
      a series of clinical and food consumption surveys among the Madrilenian
      population. There were three medical situations that were of particular relevance
      during the Civil War and after it: the pellagra epidemics, the onset of
      lathyrism, and the socalled Vallecas syndrome. The occurrence of pellagra cases
      was paramount because it allowed reconsidering all the unspecific symptoms
      observed from an already known vitamin deficiency. Pellagra became the most
      prevalent deficitrelated disease, and most clearly related to nutrition.
      Lathyrism is a chronic intoxication produced by the accumulation of neurotoxins.
      It is due to common intake of chickling peas (Lathyrus sativus). Chickling peas
      are toxic only if they represent more than 30% of the daily calories consumed for
      a prolonged period greater than two to three months. Lathyrism would reoccur in
      the Spanish population after the war, in 1941 and 1942, the so called "famine
      years", when due to the scarcity of foods chickling pea flour was again consumed
      in high amounts. Deficiency-related neuropathies observed in Madrid during the
      Civil War led to new and original clinical descriptions. In children from schools
      of the Vallecas neighborhood, a deficiency syndrome, likely related to vitamin B
      complex deficiency, was described, which manifested by muscle cramps and
      weakness, and was termed the Vallecas syndrome. Poor fat content in the diet and
      a light decrease in calcium levels, which were already very low, were observed in
      the group with cramps. Both the administration of tablets containing an adequate
      amount of calcium and phosphorus and the daily intake of 4-6 milligrams of
      thiamine, achieved a considerable reduction in the frequency and severity of the
      cramps, or their complete resolution. 

PMID- 24679013
TI  - Chinchon declaration; decalogue on low- and no-calorie sweeteners (LNCS).
AB  - Multidisciplinary experts in the areas of nutrition and health met in Chinchon,
      Madrid, on November 25-26, 2013 under the auspices of the Fundacion para la
      Investigacion Nutricional (Nutrition Research Foundation) and with the
      collaboration of the Madrid Regional Government's Health Ministry, the
      International Sweeteners Association and the Carlos III Health Institute CIBER of
      Physiopathology of Obesity and Nutrition. They analyzed the current status of
      scientific knowledge on low- and no-calorie sweeteners (LNCS) and developed a
      consensus Decalogue on their use; this constitutes the Chinchon Declaration.
      Sweeteners, including sugar, represent a subject of undeniable interest and are
      currently a popular topic, although areas relating to their safety and benefits
      remain unknown to segments of academia and the general public. The nature of LNCS
      makes them vulnerable to biased and even contradictory information. They are food
      additives that are broadly used as sugar substitutes to sweeten foods, medicines
      and food supplements when non-nutritional or non-caloric alternatives are needed.
      The Chinchon Decalogue is the outcome of a meeting for reflection and consensus
      by a group of experts with backgrounds in different scientific disciplines
      (toxicology, clinical nutrition, community nutrition, physiology, food science,
      public health, pediatrics, endocrinology and nutrition, nursing, pharmaceutical
      care and food legislation). The Decalogue includes different aspects of LNCS
      related to regulation, use, benefits and safety. In general, benefits of LNCS
      have been traditionally neglected in comparison with the tendency for emphasising
      unexisting or unproven possible risks. The need to strengthen research on LNCS in
      Spain was emphasized, as well as the need to educate both professionals and the
      public. 

PMID- 24679014
TI  - A clinical approach to the nutritional care process in protein-energy wasting
      hemodialysis patients.
AB  - INTRODUCTION: Malnutrition/wasting/cachexia are complex-disease conditions that
      frequently remain undiagnosed and/or untreated in up to 75% of prevalent
      hemodialysis (HD) patients. The nutrition care process (NCP) based on assessment,
      diagnosis, intervention and monitoring of nutritional status is a systematic
      method that nutrition professionals use to make decisions in clinical practice.
      OBJECTIVE: This review examines from a clinical-nutritional practice point of
      view: a) nutritional status as a mortality causative factor; b) phenotypic
      characteristics of malnutrition/wasting/cachexia, and c) current trends of NCP
      with special emphasis on nutritional support and novel nutrient and pharmacologic
      adjunctive therapies in HD patients. METHOD: A literature review was conducted
      using the Pubmed, Science Direct, Scielo, Scopus, and Medline electronic
      scientific basis. Studies which assessing nutritional status and nutritional
      support published from 1990 to 2013 in HD patients were included and discussed.
      RESULTS: From all the epidemiological data analyzed, NCP was the suggested method
      for identifying malnutrition/ wasting or cachexia in clinical practice. Nutrition
      support as an unimodal therapy was not completely able to reverse wasting in HD
      patients. Novel experimental therapeutic strategies including the use of appetite
      stimulants, ghrelin agonist, MC4-R antagonists, anabolic steroids, anti
      inflammatory drugs, cholecalciferol, and other components are still under
      clinical evaluation. CONCLUSION: Nutritional status is a strong predictor of
      morbidity and mortality in HD patients. The terms called malnutrition, wasting
      and cachexia have different nutritional therapeutics implications. The NCP is a
      necessary tool for assessing and monitoring nutritional status in the current
      clinical practice. Novel pharmacological therapies or specific nutrient
      supplementation interventions studies are required.

PMID- 24679015
TI  - [Modified texture diet and useful in patients with nutritional risk].
AB  - In the nutritional management of patients with dysphagia and/or elderly must make
      a multidisciplinary approach and a main tool is changing the texture of food.
      Patients with dysphagia, who need a texture modified diet, generally do not have
      a calorie and nutrient requirements different from those exhibited by people of
      the same age and sex, unless a condition or disease coexist. In these patients,
      Texture of foods should be individualized according to the patient and the time
      course of their disease. The use of texture modified diets without specifying
      produces a clear decrease in caloric and protein intakes and nutritional
      disorders. These patients may have other characteristics associated diseases,
      which would require special modification, as in the case of diabetes mellitus,
      hypertension, osteoporosis and constipation. Sometimes it is necessary to use
      artificial products to achieve different desired textures and precooked dishes,
      too.

PMID- 24679016
TI  - [Hyperuricemia and gout; the role of diet].
AB  - From ancient times, gout has been related with excessive eating and drinking;
      however, it has not been until the last decade that a broader knowledge on
      dietary factors associated with hyperuricemia and gout has been achieved.
      Obesity, excessive intake of red meats and alcoholic beverages were already
      recognized as causal factors from Antiquity. Legumes and purine rich vegetables
      have been exculpated after the studies. New risk factors, not previously
      recognized, have been described such as fructose and sweetened beverages.
      Finally, protective factors have also been described, such as skimmed dairy
      products. Gout is characterized not only by an increase in uric acid, eventual
      episodes of arthritis, and chronic joint damage, but also by association with
      several comorbidities and increased cardiovascular risk. The adoption of more
      healthier dietary habits may contribute to better management of uricemia and also
      to a reduction of associated diseases. The most common practice recommendations
      according to current knowledge and the main treatment guidelines are reviewed.
      Additional studies are needed on the actual efficacy in clinical practice of the
      adoption of specific dietary measures on the management and clinical course of
      patients with hyperuricemia and gout.

PMID- 24679017
TI  - [Adiposity as a risk factor of non alcoholic fat disease; systematic review].
AB  - INTRODUCTION: Adiposity has been described as a risk factor of nonalcoholic fatty
      liver disease (NAFLD). OBJECTIVE: To conduct a systematic review of prospective
      studies assessing risk factors of adiposity indicators for developing NAFLD.
      METHODOLOGY: All prospective studies in English and Spanish from January 2005 to
      December 2013 published in the database MEDLINE/PubMed, with a follow up greater
      than or equal to one year were reviewed. The quality of the articles was assessed
      using GRADE criteria. RESULTS: Total study population was 10,640 (6,394 men and
      4,246 women), and the age range was 20-88 years. Five prospective studies met the
      inclusion criteria and the follow-up ranged from one to seven years. The
      diagnostic criteria used were ultrasonography (4) and computed tomography (1).
      The OR of BMI, waist circumference and weight gain ranged from 1.19 to 1.43, 1.04
      to 2.15 and 1.21 to 1.57, respectively. CONCLUSION: A consistent relationship
      between adiposity indicators and NAFLD was observed.

PMID- 24679018
TI  - Bioactive vegetable proteins and peptides in lipid-lowering; nutraceutical
      potential.
AB  - As the last century saw a decline in the burden of nutritional deficiency and
      infectious disease, the global burden of chronic disease, cardiovascular disease
      (CVD) in particular, is increasing. CVD is the leading cause of death in the
      developed countries. Significant research efforts on the prevention and treatment
      of this disease have identified elevated plasma cholesterol as a primary risk
      factor for CVD. Although CVD progresses with hypercholesterolemia, it seems
      possibility to delay and prevent its development through improvement of diet.
      Recent findings demonstrate that protein concentrates, protein hydrolysates, and
      peptides derived from vegetables may promote a significant decrease in blood
      cholesterol concentration. This reduction in cholesterol and lipid levels by
      protein, protein hydrolysates, and peptides can be the result of dietary changes,
      reduced cholesterol biosynthesis, changes in bile acid synthesis, and reduced
      absorption of lipid cholesterol and bile acid. Combination drug/diet therapies
      may reduce the number of drug prescriptions, the progressive rise in "optimal"
      drug dosage and costs associated with pharmaceutical management of disease. These
      bioactive vegetable proteins, hydrolysates and peptides may be used in
      formulation of functional foods, nutraceuticals, and natural drugs because of
      their health benefit effects suggesting their use as an alternative in treatment
      of various dyslipidemias, and a potential agent for reducing cardiovascular
      diseases risk factors. 

PMID- 24679019
TI  - Clinical undernutrition in 2014; pathogenesis, early diagnosis and consequences;
      undernutrition and trophopathy.
AB  - The last ten years have allowed me to mature some concepts and criteria in
      relation to malnutrition in the clinical practice. A lot of us have devoted all
      our efforts in an attempt to take it under control. The results, however, have
      shown to be insufficient in the clinical practice, because Hospital
      Undernutrition still persists in our hospitals and in fact, its prevalence is
      growing due to an ageing population. I think it is necessary to insist in
      renaming it as Clinical Undernutrition because it not only appears in hospital
      settings but it is present before and persists even after hospitalization; the
      latter reinforces the condition by forcing a change in the habits of the patient
      and the consequences of the treatments. I would also like to sustain that the
      risk is not caused by the undernutrition in itself but rather in the disruption
      of the nutritional balance which is a consequence of the aforementioned
      conditions and which is defined in a term: Trophopathy; that is, a disruption in
      the trophism or in the normal functioning of the nutritional status. This
      disruption constitutes the core risk that is associated with clinical
      undernutrition and the physical consequences of it. The disruption occurs
      internally and it will play havoc on cellular nutrition, tissues and further. It
      appears simultaneously in the blood, so it should be searched and detected there
      as it is the closest possible place to its origin. The new therapeutic procedures
      make it possible to cure some cases that in the past were impossible to treat.
      However, this also means increased risks and so requires a strict control to
      achieve the best results. Both illness and its treatment put homeostasis at risk
      and they will definitely impact the nutritional balance, being the latter the key
      objective in order to achieve or restore the healing process and health. Apart
      from the benefit obtained with the treatment, it is necessary to apply an
      appropriate nutritional support that will guarantee the least amount of risks
      which could derive from an imbalanced nutritional status. The use of automated
      systems to predict and control the risk factors during the clinical phase makes
      it possible to have a more thorough control of the illness from its origins,
      allowing an early diagnosis and treatment of it. 

PMID- 24679020
TI  - Nutritional screening; control of clinical undernutrition with analytical
      parameters.
AB  - OBJECTIVE: To update the system for nutritional screening. The high prevalence of
      nutritional unstability that causes the Clinical Undernutrition (CU), especially
      within the hospitals and assisted residencies, makes it necessary to use
      screening tools for the constant control of undernutrition to combat it during
      its development. CU is not so much due to a nutritional deficiency but to the
      illness and its treatments. However, the screening systems currently used are
      aimed at detecting an already established undernutrition rather than at detecting
      any nutritional risk that may be present. The metabolic changes of the
      nutritional status that have a trophopathic effect, can be easily and
      automatically detected in plasma, which allows to make the necessary changes in
      treatments that might be too aggressive, as well as to apply nutritional support
      according to each case. The manual screening systems can detect those somatic
      changes typical of undernutrition only after many days or weeks, which might be
      too late. Plasma albumin is a very reliable parameter for nutritional control. A
      lowered amount of it, due to whatever reason, is a clear sign of a possible
      deficit as well as of a nutritional risk suffered by the cell way before the
      somatic signs of undernutrition will become apparent. A fast detection of
      nutritional risk, anticipating undernutrition, offers prognostic abilities, which
      makes screening tools based on analytic parameters the most useful, ergonomic,
      reliable and efficient system for nutritional screening and prognosis in the
      clinical practice. CONCLUSION: It is necessary to update some concepts, to leave
      behind old myths and to choose modern screening systems that have proven to be
      efficient. This is the only way achieving the dream of controlling CU among ill
      and vulnerable patients.

PMID- 24679021
TI  - Purple grape juice as a protector against acute x-irradiation induced alterations
      on mobility, anxiety, and feeding behaviour in mice.
AB  - The aim of this work was to test the hypothesis that a moderate intake of organic
      purple grape juice shows a positive radiomodifier effect over early behavioural
      damage following acute X-irradiation in mice. Anxiety-, locomotion-, and feeding
      related responses to 6 Gy total body X-irradiation (TBI) were studied via open
      field, Rotarod, and feeding/drinking recording. Thirty-two male mice weighing 25
      30 g were grouped according grape juice (J) or water (W) ad libitum drinking and
      either non-irradiated (N) or irradiated (R). 24 h post-TBI the access frequency
      to the center and corners of the open field was decreased, and the total stay in
      the corners increased, in RW vs. NW mice. Anxiety-related parameters decreased in
      RJ vs. RW mice. Rotarod latency times increased 72 h post-TBI in RJ vs RW mice.
      No overall changes in food and drink intake were observed along the experimental
      period. On the irradiation day, bout number was increased and bout duration was
      decreased in RW mice. The changes were reversed by purple grape juice intake.
      Grape juice intake before and after TBI can overcome several radiation-induced
      changes in behaviour within 24-72 hours after sub-lethal X-irradiation. This
      beneficial effect on short-term anxiety and mobilityrelated activities could
      probably be included in the list of flavonoid bio-effects. The present findings
      could be relevant in designing preventive interventions aimed to enhance body
      defense mechanisms against short-term irradiation damage. 

PMID- 24679022
TI  - [Maternal actions and problems in managing the child's weight and their
      association with the maternal perception of the weight and age of her child].
AB  - INTRODUCTION: To properly perceive the child's weight may influence the mother to
      start up changes to prevent and manage overweight problems. OBJECTIVES: 1) To
      assess whether the actions and problems to manage the child's weight are
      different according to the nutritional status and the perception on the child's
      weight; and 2) to assess whether the actions and problems are different according
      to the child's age. METHODS: 2840 mothers and sons/daughters (age 2-17 years)
      from North-eastern Mexico participated. The mothers answered: a) I feel my child
      is overweighted? b) What have you done to manage your son's / daughter's weight?
      and c) What are the problems? The children's weight and height were measured.
      Contingency tables were constructed and the Chi squared test was applied.
      RESULTS: When the mothers of children with overweight/ obesity properly perceive
      this situation, dietrelated actions are taken (62.0% and 65.6%) (X(2) = 307.02,
      gl = 9, p < .001) and the problems are recognized (26.2% and 43.7%) (X(2) =
      131.46, gl = 6, p < .001). The mothers of children in 1st to 6th grade are more
      prone to take actions (51.2%) (X(2) = 44.78, gl = 9, p < .001) and recognize more
      problems (21.8%) (X(2) = 61.74, gl = 6, p < .001) CONCLUSIONS: When the problems
      related with the child's weigh are recognized, actions are undertaken and the
      problems are recognized. Interventions are recommended for properly recognizing
      overweight/obesity and providing information on diet-related actions.

PMID- 24679023
TI  - [Accuracy of body mass index derived from self-reported height and weight in a
      spanish sample of children].
AB  - INTRODUCTION: In the children obesity research field, weighing and measuring
      involves high research costs, which could be reduced if the self-reported body
      mass index (BMI) was ascertained to be a valid index. OBJECTIVE: To analyze the
      accuracy of children's selfreported BMI. MATERIALS AND METHODS: 171 school
      students from Madrid participated in the study (Mean age: 10,68 years). They were
      weighed and measured, and were also asked to report their weight and height. Both
      current and selfreported BMI were calculated. RESULTS: The correlation between
      self-reported BMI and the current BMI was r = .803 (p < .001), and the kappa
      indexex ranged from k = .38 to .46. CONCLUSIONS: The self-reported BMI noticeably
      coincide with the current BMI in 10 to 11 year-old children. However, a modest
      concordance was found between the categorization within a weight-related group
      (normal, overweight and obese) based on both indexes, which shows the former
      could be a valid measure when carrying out population studies on obesity and
      overweight.

PMID- 24679024
TI  - [Zinc deficiency and associated factors in colombian children; results from the
      2010 national nutrition survey; a cross sectional study].
AB  - INTRODUCTION: Zinc (Zn) is an essential micronutrient for cell growth, protein
      synthesis and cell differentiation. This deficiency affects the growth,
      development, energy metabolism and immune response in Colombian children's.
      OBJECTIVE: To examine factors associated with Zn deficiency in a representative
      sample of Colombian children. PATIENTS AND METHODS: A cross-sectional descriptive
      study was conducted of data from the 2010 National Nutrition Survey of Colombia
      (ENSIN 2010), in 4.279 children aged between 12-59 months of age. Plasma levels
      of Zn were determined by atomic absorption spectrophotometry, and associated
      factors (sex, age, ethnicity, SISBEN score, and geographic region) were collected
      by structured questionnaire. Associations were established through a
      multivariable regression model. RESULTS: We found a range of Zn of 78.5 MUg/dl,
      (95% CI 76.7 to 80.4 MUg/dl). 43.3% (95% CI 42.2%-44.3%) of children had lower Zn
      levels to 65 MUg/dl. Children belonging to an ethnic groups (indigenous) or
      residing in rural areas; showed Zn deficiency (56.3% and 47.8%) respectively.
      Regression models show that to be indigenous (OR 1.76, 95% CI 1.29 to 2.41), and
      to reside in rural areas (OR 1.39, 95% CI 1.16 to 1.67) were associated with Zn
      deficiency. CONCLUSIONS: The study population shows a high prevalence of Zn
      deficiency, so it is recommended that comprehensive interventions which are
      involved nutritional and educational component.

PMID- 24679025
TI  - Intensive nutritional support improves the nutritional status and body
      composition in severely malnourished children with cerebral palsy.
AB  - OBJECTIVE: To demonstrate that a nutritional support intervention, via naso
      enteral tube-feeding or gastrostomy, has a significant impact on the nutritional
      status and body composition in severely malnourished children with cerebral palsy
      spastic quadriplegia. METHODS: Thirteen patients with moderate/severe
      malnutrition and cerebral palsy spastic quadriplegia who were fed via naso
      enteral tube-feeding or gastrostomy were included in a cohort study.
      Anthropometric measurements and estimated body composition by bioelectric
      impedance analysis were obtained. ANOVA and Wilcoxon tests were used. RESULTS:
      During the four weeks of nutritional recovery, an average weight increase of 2700
      g was achieved. There were significant increases in anthropometric indicators,
      including BMI and weight/length (p < 0.01). The increase in arm fat area was
      significantly higher than the increase in arm muscle area (104.5 vs 17.5%).
      CONCLUSION: Intensive nutritional support for four weeks had a significant effect
      on the nutritional status and body composition of severe and moderately
      malnourished children with cerebral palsy spastic quadriplegia.

PMID- 24679026
TI  - [Use of fish oil lipid emulsions in hospitalized patients under 18 years old with
      abnormal results in liver tests associated with total parental nutrition].
AB  - INTRODUCTION: Prolonged Total Parental Nutrition (TPN) is associated with life
      threatening complications in the pediatric population, being cholestasis one of
      the most important ones. The source of fatty acids, the amount of phytosterols
      and the dose of lipids in the nutritional support, have been linked to the
      development of this complication. PURPOSE: To describe the behavior of liver
      function tests in pediatric patients with TPN where lipid based omega 3 fatty
      acids (OmegavenR) were used. METHODS: A retrospective research was made in a
      population of children under 18 years old where omega 3 fatty acids were used for
      a minimum of 8 days. Patients were initially classified into two groups:
      cholestasis and abnormal liver tests. Levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB)
      gamma glutamyl transferase (GGT) and alkaline phosphatase (AP) before and after
      treatment with OmegavenR was evaluated. RESULTS: 33 patients met the inclusion
      criteria. At the end of treatment with OmegavenR, 82.4% of patients who initially
      presented cholestasis showed resolution or improvement. The group of patients
      with abnormal liver tests 18.8% progressed to cholestasis. CONCLUSIONS: Our study
      suggests that the use of OmegavenR in pediatric patients with TPN and DB >= 2
      mg/dL, seem to reverse or improve cholestasis while in patients with abnormal
      liver tests we still don't have clear effect.

PMID- 24679027
TI  - [Breastfeeding and cognitive development; interference evaluation by "5 digits
      test"].
AB  - BACKGROUND AND OBJECTIVE: Different publications have analyzed the possible
      correlation between breastfeeding length and a better cognitive development
      during school age. The present study evaluates the possible long term beneficial
      effects of breastfeeding during the first months of life on the cognitive
      development, as well as its possible role on the attention deficit and
      hyperactivity prevention. Currently this evaluation is of special interest
      considering the increasing number in western societies of childhood attention
      deficits, with or without, hyper - activity disorders. MATERIAL AND METHODS: 103
      children, during the first year of elementary education, 6 years of age (47 boys
      and 56 girls), were recruited in different schools of the Granada province,
      including urban, semi-urban and rural areas. The speed of cognitive processing
      and the ability to focus attention and reorient after an incident of distraction,
      using the five digits test (5-DGT), - variant of the Stroop interference test-
      were analyzed. RESULTS: Data show a linear correlation between longer
      breastfeeding and better scores in the test. Particularly significant (P <=
      0.001) are the reading and alternation tests for children who were breastfed for
      6 months when compared with those that only received this nutrition during their
      first month of life. CONCLUSION: This study validates the initial hypothesis,
      showing faster resolution speed and less interference in the group of children
      breastfed, at least during the first 6 months of life. Further well designed
      studies are necessary for reinforced breastfeeding recommendation, at least
      during the first 6 months of life, for children underclinical suspicion of
      possible ADHD development.

PMID- 24679028
TI  - [Nutritional content of food, and nonalcoholic beverages advertisements
      broadcasted in children's slot of Colombian national television].
AB  - OBJECTIVE: To describe the nutritional content of foods and non-alcoholic
      beverages advertised in the children's frame vs. the general frame in two
      national, private, free-access, television channels in Colombia. METHODS: Cross
      sectional, descriptive study. The recording was performed in July of 2012, for
      four days randomly chosen from 6:00 am to 12:30 pm. The nutritional content was
      classified according to the nutritional profiles criteria of the Food Standards
      Agency for risk-indicating nutrients, the Health Pan-American Organization for
      trans fat, and the 333 Colombian Resolution of 2011 that classifies foods as
      source of protecting nutrients. Descriptive statistics were used, the Kolmogorov
      Smirnov test to establish the normality, and the Chi square test for variables
      comparison. A p value < 0.05 was considered. RESULTS: During 52 hours of
      recording, 1560 commercials were shown, of which 23.3% (364), advertised foods
      and beverages, of which 56.3% were shown within the children's frame. Regarding
      the nutritional content, a high percentage of foods and non-alcoholic beverages
      classified as "rich" in sugar, sodium, saturated fat was observed within the
      children's' frame (69.0%, 56.0%, 57.1%), as compared to the general frame. By
      contrast, the percentage of foods and nonalcoholic beverages classified as "rich"
      in total fat was higher in the general frame as compared to the children's frame
      (70.4% vs. 29.6%, respectively). CONCLUSIONS: Higher exposure to advertising of
      foods and non-alcoholic beverages was observed within the children's' frame,
      characterized by high content of risk-indicating nutrients and low content of
      foods and non-alcoholic beverages with protective nutrients.

PMID- 24679029
TI  - Metabolic syndrome and associated factors in children and adolescents of a
      Brazilian municipality.
AB  - BACKGROUND: the risk factors associated to metabolic syndrome (MS) have been
      extensively studied in adults, but in children and adolescents it is poorly
      explored. OBJECTIVE: To identify the prevalence of MS and associated factors in
      children and adolescents. METHODS: A cross-sectional study with 540 children and
      adolescents from 7 to 14 years of age. The socioeconomic, demographic and
      lifestyle data and the family history of chronic diseases were reported by the
      individual and/or guardian and recorded in a structured questionnaire.
      Biochemical tests (fasting blood glucose, triacylglycerols, reduced high-density
      lipoprotein, very-low-density lipoprotein, homocysteine and cysteine), an
      anthropometric assessment and a blood pressure measurement were performed. MS was
      defined according to the criteria of The National Cholesterol Education Program
      Adult Treatment Panel III adapted by Ferranti. A Poisson regression was used to
      identify the factors statistically associated with MS. RESULTS: The MS prevalence
      was 12.8%, in which the most frequent component was a decreased high-density
      lipoprotein level (58.2%), followed by hypertriglyceridemia (41.8%), elevated
      blood pressure (29.1%), increased waist circumference (26.7%) and hyperglycemia
      (7.2%). Associations between metabolic syndrome and overweight [prevalence ratio
      (PR): 2.2 (1.22-3.95)], father education [PR: 2.19 (1.10-4.37)], serum very low
      density lipoprotein concentration [PR: 1.08 (1.04-1.11)] and concomitantly
      increased serum homocysteine and cysteine concentrations [PR: 2.58 (1.32-5.04)]
      were observed. CONCLUSIONS: The MS prevalence is high in children and adolescents
      and it is increased in patients with overweight, higher father education,
      increased serum very-low-density lipoprotein concentrations and a concomitant
      serum homocysteine and cysteine high levels.

PMID- 24679030
TI  - [Texture modified diet; digestibility, nutritional value, and contributions to
      menu of hospitals and nursing homes].
AB  - Texture modified diet is a significant loss of the organoleptic qualities of the
      feed, so often associated with suboptimal intake and can increase the risk of
      malnutrition in people with chewing or swallowing difficulties. It is known that
      these diets based on traditional ground, have varying nutritional adequacy. The
      emergence of numerous commercial products lyophilized or ready to eat, with a
      wide variety of nutritional value, according to the range and recipe is
      concerned, represent an important step in the normalization of nutritional value
      and food security in people with dysphagia. This review discussed the possible
      advantages or disadvantages compared to traditional ground, and the possibilities
      of inclusion in the menu of hospitals and nursing homes. 

PMID- 24679031
TI  - Estimation of antioxidants dietary intake in wet age-related macular degeneration
      patients.
AB  - AIMS: The aim of this study was to estimate the intake of antioxidant nutrients
      in wet age-related macular degeneration (AMD) patients, a degenerative and
      progressive disorder of the macula, which is the central part of the retina,
      associated with central vision loss. METHODS: A sample (n = 52, 78.9 +/- 6.6
      years old, 40.4% females and 59.6% males) of patients diagnosed of AMD was
      interviewed. Anthropometric measurements, two 24- h recalls, a semi-quantitative
      food frequency questionnaire and a general questionnaire incorporating questions
      related to socio-demographic and lifestyle variables were used. RESULTS: Most of
      wet AMD patients showed inadequate antioxidant nutrient intake (< 2/3 of
      Recommended Dietary Intake, RDI), and more than 60% of patients showed serious
      deficient intake (< 1/3 RDI) of lutein and zeaxanthin. Most consumed antioxidant
      rich foods only represented low contributions to antioxidant intake. Although
      adiposity is a factor risk for AMD progression; the fat and saturated fatty acids
      (SFA) intake of study participants were higher than the recommendations; the
      prevalence of overweight was 61.9% men and 58.1% in women; and 83% of patients
      (90.5% men and 77.4% women) showed fat mass over the cut-off limits. CONCLUSIONS:
      The food pattern of wet AMD patients should be improved by means of an increase
      in the consumption of antioxidant rich foods, and a decrease in SFA rich foods.L.

PMID- 24679032
TI  - [Roles of rs 6923761 gene variant in glucagon-like peptide 1 receptor on weight,
      cardiovascular risk factor and serum adipokine levels in morbid obese patients].
AB  - BACKGROUND: Studies of the GLP-1 receptor have been directed at identifying
      polymorphisms in the GLP-1 receptor gene that may be a contributing factor in the
      pathogenesis of diabetes mellitus and cardiovascular risk factors. Nevertheless,
      the role of GLP-1 variants on body weight, cardiovascular risk factors and
      adipokines remains unclear in obese patients. OBJECTIVE: Our aim was to analyze
      the effects of rs6923761 GLP-1 receptor polymorphism on body weight,
      cardiovascular risk factors and serum adipokine levels in morbid obese patients.
      DESIGN: A sample of 175 morbid obese patients was enrolled in a prospective way.
      Basal fasting glucose, c-reactive protein (CRP), insulin, insulin resistance
      (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides
      concentration and adipokines were measured. Weights, body mass index, waist
      circumference, fat mass by bioimpedance and blood pressure measures were
      measured. RESULTS: 87 patients (49,7%) had genotype GG and 88 (50,3%) had; GA (71
      patients, 40,6%) or AA (17 patients, 9,7%) (second group). In the group with GG
      genotype, levels of glucose (4,4 +/- 2,3 mg/dl, p < 0,05), tryglicerides (6,8 +/-
      4,3 mg/dl , p < 0,05), insulin (4,5 +/- 2,3 UI/l , p < 0,05) and HOMA (1,5 +/-
      0,9 units, p < 0,05) were higher than mutant group. No differences were detected
      in other parameters. CONCLUSION: Data from our study revealed an association with
      metabolic parameters and rs6923761. Levels of triglycerides, insulin and HOMA
      were higher in subjects with A alelle than non A allele subjects.

PMID- 24679034
TI  - [Association between malnutrition and depression in elderly].
AB  - BACKGROUND: Malnutrition and depression are common geriatric disorders. The aim
      of this study was determined the prevalence of malnutrition and depression in the
      elderly, as well as assess the association between depression and malnutrition.
      METHODS: A cross-sectional study was done with elderly of external consult in a
      Public Specialized Hospital of Mexico City. The nutritional status was classified
      by the Mini Nutritional Assessment (MNA) and Quetelet's Index was categorized
      according to The World Health Organization. Depression was assessed using the
      Geriatric Depression Scale (GDS). The functional autonomy indicators were
      obtained by Katz Index. Differences between groups were analyzed using the
      Chisquare test and t-test. The associations between the MNA and GDS and
      determination of risk factors for malnutrition were analyzed using multivariate
      analysis and the odds ratio (OR) estimates were determined. RESULTS: 96 patients
      were included, 79.2 female; 15.5% were classified as adequate nutritional status,
      72.2% were classified as being at risk of malnutrition and 11.3% as malnourished.
      The prevalence of depression was reported by 63.9%. Multiple logistic regression
      analysis revealed that depression and male sex are independent predictors of
      malnutrition. Depression was positively associated with the risk of malnutrition
      OR 2.4 (95% CI 0.79-7.38). For individuals male the OR for malnutrition was 1.42
      (95% CI 1.0-2.0). CONCLUSION: Depression and male sex was associated with the
      risk of malnutrition in the elderly.

PMID- 24679033
TI  - [Physical fitness evolution in octogenarian population and its relationship with
      a sedentary lifestyle].
AB  - OBJECTIVE: The aim of this study was to determine the changes in physical fitness
      over two years of following up in octogenarian people and to check whether a
      sedentary lifestyle modify these variations. METHODS: Physical fitness of 182
      subject (48 men, 134 women) with a mean age of 82,3 +/- 2,3 years were evaluated
      using 8 different tests. A repeated measures analysis was carried out to see the
      differences between the two evaluation periods and to see the physical fitness
      differences between sedentary people (sit >= 4 hours/day) and non sedentary
      people (sit < 4 hours/day). RESULTS: Between the two evaluation periods, we found
      a significant decrease in the agility test (p < 0.05), walking speed (p < 0.01)
      and endurance (p < 0.01). In relation to the subjects who spent sitting 4
      hours/day there was a decrease in the walking speed test between the two
      evaluations (p < 0.05). Moreover, there was a decrease of walking speed and
      endurance between the two evaluation periods in both sedentary and nonsedentary
      people (p < 0.05). CONCLUSION: In two years of following up, there are adverse
      changes in the level of physical fitness in octogenarians. Long periods of
      sitting time may translate into a loss of agility. Walking speed and endurance
      seem to be the components of physical fitness more affected by the ageing process
      in this population; and this loss is not determined by the hours of sitting per
      day.

PMID- 24679035
TI  - Dietary intake and nutritional status in cancer patients; comparing adults and
      older adults.
AB  - OBJECTIVE: Evaluate the nutrient intake and nutritional status of food in cancer
      patients admitted to a university hospital, with comparison of adult and older
      adult age category. METHODS: Cross-sectional study. This study involved cancer
      patients admitted to a hospital in 2010. Dietary habits were collected using a
      Brazilian food frequency questionnaire. Participants were divided in two groups:
      adults or older adults and in 4-cancer category: hematologic, lung,
      gastrointestinal and others. Body Mass Index evaluated nutritional status.
      RESULTS: A total of 86 patients with a mean age of 56.5 years, with 55% males and
      42% older adults were evaluated. The older adult category had a higher frequency
      of being underweight (24.4% vs 16.3%, p < 0.01) and a lower frequency of being
      overweight (7% vs. 15.1%, p < 0.01) than adults. Both, adult and older adults had
      a high frequency of smoking, alcohol consumption and physical inactivity. The
      older adults had lower consumption of calories, intake of iron and folic acid.
      Inadequacy of vitamin intake was observed in both groups; respectively, 52%, 43%,
      95%, 76% and 88% for Vitamin A, C, D, E and folic acid. The older adults had a
      higher folic acid and calcium inadequacy than the adults (97% vs 82%, p <0.01;
      88% vs 72%, p < 0.01). There was no association of micronutrient intake with
      cancer, nor with nutritional status. CONCLUSION: The food intake, macro and
      micronutrients ingestion is insufficient among cancer individuals. Food intake of
      older adults was inferior, when compared to the adult category. There was a high
      prevalence of BMI excess in the adult group and a worst nutritional status in the
      older adult category.

PMID- 24679036
TI  - Changes in body composition of high competition rugby players during the phases
      of a regular season; influence of diet and exercise load.
AB  - BACKGROUND: Top athletes are subjected to intense training to achieve high
      performance. There are factors such as diet and strenuous exercise that affects
      body composition and can modify the performance. The aim of the study was to
      evaluate the effect of a personalized plan of diet and training on body
      composition. METHODS: We studied the body composition of 18 professional rugby
      players using Kinanthropometry parameters. The study was conducted from the
      preseason to the end of the season taking into account the position of the player
      for measuring exercise intensity, and developing a personalized nutritional and
      training plan to each player. RESULTS: At baseline the players were away from the
      internationally recommended body composition, with high percentages of body fat.
      Appropriate and personalized diet plans and training custom achieved fat
      percentages close to those recommended. CONCLUSIONS: The personalized program of
      diet and training directed has adequate leverage to improve all parameters
      studied them bringing them as close to the ideal.

PMID- 24679037
TI  - High prevalence of inactivity among young patients with type 1 diabetes in south
      Spain.
AB  - OBJECTIVES: To describe usual physical activity level and analyze its association
      with metabolic control and presence of microvascular complications in a cohort of
      patients with type 1 diabetes (DM-1) in south Spain. METHODS: Observational,
      cross-sectional study that included one hundred thirty patients, aged 33.9 +/-
      11.5 years-old with disease duration of 16.5 +/- 9.5 years that consecutively
      were recruited among patients attending the Endocrinology Service of Puerta del
      Mar University Hospital (Cadiz, Spain). Usual physical activity level was
      assessed using the "General Practice Physical Activity Questionnaire" (GPPAQ)
      together with clinical, anthropometric, metabolic parameters and microvascular
      complications. RESULTS: DM-1 patients were grouped in four categories of physical
      activity level: inactive (n = 33; 25.3%), moderately inactive (n = 31; 23.8%),
      moderately active (n = 26; 20.0%) and active (n = 40; 30.9%). We observed no
      significant differences in glycated haemoglobin (HbA1c) level between the
      different physical activity groups analyzed. Patients classified as moderately
      active and active were more often men, significantly younger and presented lower
      plasmatic levels of triglycerides than patients classified as inactive or
      moderately inactive, with no differences in other clinical or anthropometric
      variables. In addition, active and moderately active patients had a lower
      prevalence of diabetic retinopathy and microvascular complications in general
      compared to inactive or moderately inactive patients. CONCLUSIONS: Half of
      patients with type 1 diabetes evaluated were classified as inactive and these
      patients had a higher prevalence of diabetic retinopathy than active patients. No
      difference in HbA1c levels was documented among different groups of physical
      activity.

PMID- 24679038
TI  - [Calibration tools menu and calculation of the composition nutritional food;
      validity and variability].
AB  - INTRODUCTION: Food composition tables (FCT) are a basic tool to know the energy
      content and the nutritional composition of foods. OBJECTIVES: To demonstrate
      through a model menu the existent variability between the different FCTs and the
      databases of the software used. METHODS: A menu was calibrated by using the
      Alimentador software, which was then validated with the software DIAL, EasyDiet,
      and with RedBEDCA, CESNID, Mataix, 2003 y Moreiras O., 2013 FCTs. RESULTS: many
      nutrients could not be compared due to the lack of data. The range of comparable
      data obtained for each nutrient may vary from 8% to 84%, being wider for
      micronutrients than for macronutrients or energy. CONCLUSION: We have shown the
      variability between FCTs and some software programs, which gives way to question
      the scientific validity of the use of these tools that frequently used by
      nutrition professionals.

PMID- 24679039
TI  - Serum uric acid can predict higher C-reactive protein levels in apparently
      healthy men.
AB  - INTRODUCTION: Epidemiological studies have shown an association between coronary
      heart disease and emerging cardiovascular risk factors, such as, levels of
      fibrinogen and high-sensitivity C-reactive protein (hs-CRP). OBJECTIVES: To
      verify the ability of biochemical indicators in discriminating changes in the
      levels of hs-CRP and fibrinogen, in apparently healthy adult men. METHODS: Were
      evaluated 130 apparently healthy men (20-59 years), having measurement of weight
      and height. Biochemical measurements (lipid profile, fasting glucose, uric acid,
      hs-CRP and fibrinogen) were performed. Body mass index, total cholesterol/HDL-c
      and LDL-c/HDL-c ratios were calculated. It was considered as the cutoff point for
      hs-CRP values >= 0.12 mg/dL and for fibrinogen the 50th percentile of the
      evaluated sample. RESULTS: The uric acid showed the best correlation (r = 0.325)
      and the higher area under the ROC curve (0.704 +/- 0.054), showing greater
      ability to discriminate higher levels of hs-CRP (p < 0.01). The total
      cholesterol/HDL-c ratio (r = 0.222) and the LDL-c/HDL-c ratio (r = 0.235) showed
      the best correlations and the higher areas under the ROC curves (0.624 +/- 0.049
      and 0.624 +/- 0.049) in identify higher levels of fibrinogen (p < 0.05).
      CONCLUSION: The uric acid and the total cholesterol/HDL-c and the LDL-c/HDL-c
      ratios showed greater ability to identify changes in the levels of hs-CRP and
      fibrinogen, respectively. It was suggested the use of biochemical markers in the
      clinical practice, in order to establish preventive action for cardiovascular
      disease in apparently healthy adult men.

PMID- 24679040
TI  - [Emotional processing in adult vs adolescent patients with eating behavior
      disorders; emotional recognizing and the mental theory].
AB  - OBJECTIVE AND METHODS: Current research has focused on the impact of difficulties
      in emotional recognition and regulation and deficits in social cognition (ToM) in
      the predisposition and maintenance of eating disorders EDs. Though most studies
      have assessed adult patients, few studies have examined these characteristics in
      adolescent patients. This study assessed difficulties in emotional recognition
      and ToM in 48 adult and adolescent patients (39 Anorexia Nervosa patients, and 9
      Bulimia Nervosa patients) of varying degrees of severity, who were compared with
      a group of healthy controls using the TAS-20, and the RME. RESULTS: The results
      substantiate the initial working hypothesis that difficulties in emotional
      recognition would be greater in both AN and BN patients as compared to controls.
      Moreover, these difficulties were modulated by age and the severity of the
      disorder i.e., severely affected adult patients had more difficulties in
      emotional recognition than less severely affected adolescent patients. No
      differences were observed according to diagnosis or BMI. Contrary to expectation
      in terms of the functioning of social cognition (theory of mind), both adult and
      adolescent AN and BN patients maintained their ability to infer the mental state
      of others, and performance in mentalizing task was similar to controls.
      Performance was slightly lower, but not statistically significant, in longterm
      previously treated patients than in controls. No relationship with low BMI or
      eating symptoms was observed. CONCLUSION: Since all of the ED patients exhibited
      emotional difficulties, techniques designed to enhance emotional recognition are
      vital for successful treatment. As difficulties become more acute as the disorder
      progresses, the treatment of adolescent patients must entail early therapeutic
      interventions designed to arrest further deterioration. In terms of ToM, the
      results suggest difficulties in social cognition can neither be generalized to
      all AN patients nor to those suffering from severe malnutrition. In long-term
      patients mentalization was slightly low and apparently poorly associated to
      difficulties in therapeutic link. These results do not lend support to the
      hypothesis that AN patients share the characteristics of patients affected by
      autistic spectrum disorders, at least not in terms of all the dimensions of ToM.
      These, and other controversial findings in the social cognition of EDs suggest
      that difficulties in mentalization cannot be generalized to all ED patients,
      which underscores the need for further research on the differential
      characteristics of AN patients with ToM disorders that goes beyond the emotional
      difficulties observed.

PMID- 24679041
TI  - [The X of dyslipemias].
AB  - Patients with cholestatic diseases can present secondary hypercholesterolemia, as
      a result of the accumulation of lipoprotein X (Lp-X); an abnormal LDL form,
      considered as the biochemical parameter more sensitive and specific for the
      diagnosis of cholestasis intra or extrahepatic cholestasis. The aim of this
      clinical communication is to illustrate this association. A 54-year-old male with
      severe cholestatic liver disease which in turn presents a progressive total
      cholesterol rise and LDL with presence of lipoprotein X. Total and LDL
      cholesterol were down to normal, also coinciding with the improvement of
      cholestatic liver disease conferring cardiovascular protection pattern.

PMID- 24679042
TI  - The crystal and electronic structures of Cd(3)As(2), the three-dimensional
      electronic analogue of graphene.
AB  - The structure of Cd3As2, a high-mobility semimetal reported to host electrons
      that act as Dirac particles, is reinvestigated by single-crystal X-ray
      diffraction. It is found to be centrosymmetric rather than noncentrosymmetric as
      previously reported. It has a distorted superstructure of the antifluorite (M2X)
      structure type with a tetragonal unit cell of a = 12.633(3) and c = 25.427(7) A
      in the centrosymmetric I41/acd space group. The antifluorite superstructure can
      be envisioned as consisting of distorted Cd6?2 cubes (where ? = an empty cube
      vertex) in parallel columns, stacked with opposing chirality. Electronic
      structure calculations performed using the experimentally determined
      centrosymmetric structure are similar to those performed with the inversion
      symmetry absent but with the important implication that Cd3As2 is a three
      dimensional (3D)-Dirac semimetal with no spin splitting; all bands are spin
      degenerate and there is a 4-fold degenerate bulk Dirac point at the Fermi energy
      along Gamma-Z in the Brillouin zone. This makes Cd3As2 a 3D electronic analogue
      of graphene. Scanning tunneling microscopy experiments identify a 2 * 2 surface
      reconstruction in the (112) cleavage plane of single crystals; needle crystals
      grow with a [110] long axis direction. 

PMID- 24679043
TI  - Microbial synthesis of pinene.
AB  - The volumetric heating values of today's biofuels are too low to power energy
      intensive aircraft, rockets, and missiles. Recently, pinene dimers were shown to
      have a volumetric heating value similar to that of the tactical fuel JP-10. To
      provide a sustainable source of pinene, we engineered Escherichia coli for pinene
      production. We combinatorially expressed three pinene synthases (PS) and three
      geranyl diphosphate synthases (GPPS), with the best combination achieving ~28
      mg/L of pinene. We speculated that pinene toxicity was limiting production;
      however, toxicity should not be limiting at current titers. Because GPPS is
      inhibited by geranyl diphosphate (GPP) and to increase flux through the pathway,
      we combinatorially constructed GPPS-PS protein fusions. The Abies grandis GPPS-PS
      fusion produced 32 mg/L of pinene, a 6-fold improvement over the highest titer
      previously reported in engineered E. coli. Finally, we investigated the pinene
      isomer ratio of our pinene-producing microbe and discovered that the isomer
      profile is determined not only by the identity of the PS used but also by the
      identity of the GPPS with which the PS is paired. We demonstrated that the GPP
      concentration available to PS for cyclization alters the pinene isomer ratio.

PMID- 24679044
TI  - Prenylated benzoylphloroglucinols and xanthones from the leaves of Garcinia
      oblongifolia with antienteroviral activity.
AB  - An acetone extract of the leaves of Garcinia oblongifolia showed antiviral
      activity against enterovirus 71 (EV71) using a cytopathic effect inhibition
      assay. Bioassay-guided fractionation yielded 12 new prenylated
      benzoylphloroglucinols, oblongifolins J-U (1-12), and five known compounds. The
      structures of 1-12 were elucidated by spectroscopic analysis including 1D- and 2D
      NMR and mass spectrometry methods. The absolute configurations were determined by
      a combination of a Mosher ester procedure carried out in NMR tubes and ECD
      calculations. Compared to ribavirin (IC50 253.1 MUM), compounds 1, 4, and 13
      exhibited significant anti-EV71 activity in vitro, with IC50 values of 31.1,
      16.1, and 12.2 MUM, respectively. In addition, the selectivity indices of these
      compounds were 1.5, 2.4, and 3.0 in African green monkey kidney (Vero) cells,
      respectively. 

PMID- 24679045
TI  - Ethnoveterinary medicines in four districts of Jimma zone, Ethiopia: cross
      sectional survey for plant species and mode of use.
AB  - BACKGROUND: Traditional medicines have been used for nearly 90% of livestock
      populations in Ethiopia where complimentary remedies are required to the modern
      health care system. All plants with pharmacological activity complimentarily
      prescribed as best choice against livestock diseases. A community based cross -
      sectional survey was conducted to investigate ethno-veterinary knowledge and
      practices of study area by purposive sampling techniques. The data from
      respondents were collected through face-to face interview using pre-tested semi
      structured questionnaires, which was further accompanied by field observations of
      the medicinal plants. The vast majority of the statistics were analyzed
      descriptively by SPSS 16 Windows version to extrapolate our findings in ethno
      botanical knowledge. RESULTS: In the study, a total of 74 species of
      ethnoveterinary medicinal plant species from 31 families have been identified for
      treating 22 different livestock ailments. The three families: Asteraceae,
      Cucurbitaceae and Solanaceae make up larger proportion of reported medicinal
      plants which accounted for 10.41%, 8.33% and 6.25%, respectively. Of reported
      medicinal plants, 16.7% informant consensus was recorded for the species Croton
      macrostachyus Del., 10.7% for Nicotiana tabacum L. and 9.5% for Olea capensis
      L.Subsp. macrocarpa (C.H. Wright) I.Verd. in treatment of one or more veterinary
      ailments. The greater varieties of medicinal plant species that accounted for
      28.2% were used against management of blackleg which was common livestock
      diseases in the study area. The findings showed, trees accounted for 43.24%,
      followed by shrubs (33.78%) and herbs (14.86%). Eighty one percent of medicinal
      plants reported by respondents were collected from wild habitats, and leaves
      reported to be used by 68% of the informants for ethnoveterinary medicines
      preparations. The preparations were applied through different routes of
      administration; oral administration accounted for (76.2%), followed by
      application of topical (9.53%) and nasal (5.19%). CONCLUSIONS: Ethnoveterinary
      practices significantly suggested to play greater roles in livestock health care
      as an alternative or integral part of modern veterinary practices. The
      traditional knowledge in treatment of livestock diseases of the study districts
      needs further scientific evaluations by phytochemical and antimicrobial
      experimentation to determine safety, efficacy, mode of delivery, drug development
      and dosage in pharmacological laboratory.

PMID- 24679046
TI  - Efficacy of oxytocin administration early after psychotrauma in preventing the
      development of PTSD: study protocol of a randomized controlled trial.
AB  - BACKGROUND: Currently few evidence based interventions are available for the
      prevention of PTSD within the first weeks after trauma. Increased risk for PTSD
      development is associated with dysregulated fear and stress responses prior to
      and shortly after trauma, as well as with a lack of perceived social support
      early after trauma. Oxytocin is a potent regulator of these processes. Therefore,
      we propose that oxytocin may be important in reducing adverse consequences of
      trauma. The 'BONDS' study is conducted in order to assess the efficacy of an
      early intervention with intranasal oxytocin for the prevention of PTSD.
      METHODS/DESIGN: In this multicenter double-blind randomized placebo-controlled
      trial we will recruit 220 Emergency Department patients at increased risk of
      PTSD. Trauma-exposed patients are screened for increased PTSD risk with
      questionnaires assessing peri-traumatic distress and acute PTSD symptoms within 7
      days after trauma. Baseline PTSD symptom severity scores and neuroendocrine and
      psychophysiological measures will be collected within 10 days after trauma.
      Participants will be randomized to 7.5 days of intranasal oxytocin (40 IU) or
      placebo twice a day. Follow-up measurements at 1.5, 3 and 6 months post-trauma
      are collected to assess PTSD symptom severity (the primary outcome measure).
      Other measures of symptoms of psychopathology, and neuroendocrine and
      psychophysiological disorders are secondary outcome measures. DISCUSSION: We
      hypothesize that intranasal oxytocin administered early after trauma is an
      effective pharmacological strategy to prevent PTSD in individuals at increased
      risk, which is both safe and easily applicable. Interindividual and contextual
      factors that may influence the effects of oxytocin treatment will be considered
      in the analysis of the results. TRIAL REGISTRATION: Netherlands Trial Registry:
      NTR3190.

PMID- 24679047
TI  - CXCR3 deficiency enhances tumor progression by promoting macrophage M2
      polarization in a murine breast cancer model.
AB  - Tumor associated macrophages play a vital role in determining the outcome of
      breast cancer. We investigated the contribution of the chemokine receptor CXCR3
      to antitumor immune responses using a cxcr3 deficient mouse orthotopically
      injected with a PyMT breast cancer cell line. We observed that cxcr3 deficient
      mice displayed increased IL-4 production and M2 polarization in the tumors and
      spleens compared to WT mice injected with PyMT cells. This was accompanied by
      larger tumor development in cxcr3(-/-) than in WT mice. Further, tumor-promoting
      myeloid derived immune cell populations accumulated in higher proportions in the
      spleens of cxcr3 deficient mice. Interestingly, cxcr3(-/-) macrophages displayed
      a deficiency in up-regulating inducible nitric oxide synthase after stimulation
      by either IFN-gamma or PyMT supernatants. Stimulation of bone marrow derived
      macrophages by PyMT supernatants also resulted in greater induction of arginase-1
      in cxcr3(-/-) than WT mice. Further, cxcr3(-/-) T cells activated with CD3/CD28
      in vitro produced greater amounts of IL-4 and IL-10 than T cells from WT mice.
      Our data suggests that a greater predisposition of cxcr3 deficient macrophages
      towards M2 polarization contributes to an enhanced tumor promoting environment in
      cxcr3 deficient mice. Although CXCR3 is known to be expressed on some
      macrophages, this is the first report that demonstrates a role for CXCR3 in
      macrophage polarization and subsequent breast tumor outcomes. Targeting CXCR3
      could be a potential therapeutic approach in the management of breast cancer
      tumors. 

PMID- 24679049
TI  - Wafer-scale fabrication of self-catalyzed 1.7 eV GaAsP core-shell nanowire
      photocathode on silicon substrates.
AB  - We present the wafer-scale fabrication of self-catalyzed p-n homojunction 1.7 eV
      GaAsP core-shell nanowire photocathodes grown on silicon substrates by molecular
      beam epitaxy with the incorporation of Pt nanoparticles as hydrogen evolution
      cocatalysts. Under AM 1.5G illumination, the GaAsP nanowire photocathode yielded
      a photocurrent density of 4.5 mA/cm(2) at 0 V versus a reversible hydrogen
      electrode and a solar-to-hydrogen conversion efficiency of 0.5%, which are much
      higher than the values previously reported for wafer-scale III-V nanowire
      photocathodes. In addition, GaAsP has been found to be more resistant to
      photocorrosion than InGaP. These results open up a new approach to develop
      efficient tandem photoelectrochemical devices via fabricating GaAsP nanowires on
      a silicon platform. 

PMID- 24679048
TI  - Frequency of APOE, MTHFR and ACE polymorphisms in the Zambian population.
AB  - BACKGROUND: Polymorphisms within the apolipoprotein-E (APOE),
      Methylenetetrahydrofolate reductase (MTHFR) and Angiotensin I-converting enzyme
      (ACE) genes has been associated with cardiovascular and cerebrovascular
      disorders, Alzheimer's disease and other complex diseases in various populations.
      The aim of the study was to analyze the allelic and genotypic frequencies of
      APOE, MTHFR C677T and ACE I/D gene polymorphisms in the Zambian population.
      RESULTS: The allele frequencies of APOE polymorphism in the Zambian populations
      were 13.8%, 59.5% and 26.7% for the epsilon2, epsilon3 and epsilon4 alleles
      respectively. MTHFR C677T and ACE I/D allele frequencies were 8.6% and 13.8% for
      the T and D minor alleles respectively. The epsilon2epsilon2 genotype and TT
      genotype were absent in the Zambian population. The genetic distances between
      Zambian and other African and non-African major populations revealed an
      independent variability of these polymorphisms. CONCLUSION: We found that the
      APOE epsilon3 allele and the I allele of the ACE were significantly high in our
      study population while there were low frequencies observed for the MTHFR 677 T
      and ACE D alleles. Our analysis of the APOE, MTHFR and ACE polymorphisms may
      provide valuable insight into the understanding of the disease risk in the
      Zambian population.

PMID- 24679050
TI  - Purification of bovine serum paraoxonase and its immobilization on Eupergit C 250
      L by covalent attachment.
AB  - Serum paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme
      that protects lipoproteins, both low-density lipoprotein (LDL) and HDL, against
      oxidation, and is considered as an antioxidative/anti-inflammatory component of
      HDL. In this study, PON1 was purified from bovine serum by ammonium sulfate
      precipitation and hydrophobic interaction chromatography on sepharose-4B-l
      tyrosine-1-napthylamine. It was then immobilized on an unmodified Eupergit(r) C
      250 L support. The immobilized PON1 retained a high catalytic activity and showed
      increased thermal stability compared to the native enzyme.

PMID- 24679051
TI  - Transport mechanisms of a novel antileukemic and antiviral compound 9-norbornyl-6
      chloropurine.
AB  - 6-Chloropurines substituted at the position 9 with variously modified bicyclic
      skeletons represent promising antiviral and anticancer agents. This work aimed to
      investigate the transport mechanisms of 9-[(1R*,2R*,4S*)-bicyclo[2.2.1]hept-2-yl]
      6-chloro-9H-purine (9-norbornyl-6-chloropurine, NCP) and their relationship to
      the metabolism and biological activity of the compound. Transport experiments
      were conducted in CCRF-CEM cells using radiolabeled compound ([(3)H]NCP). The
      pattern of the intracellular uptake of [(3)H]NCP in CCRF-CEM cells pointed to a
      combination of passive and facilitated diffusion as prevailing transport
      mechanisms. NCP intracellular metabolism was found to enhance its uptake by
      modifying NCP concentration gradient. The transport kinetics reached steady state
      under the conditions of MRP and MDR proteins blockade, indicating that NCP is a
      substrate for these efflux pumps. Their inhibition also increased the
      cytotoxicity of NCP. Our findings suggest that the novel nucleoside analog NCP
      has potential to become a new orally available antileukemic agent due to its
      rapid membrane permeation.

PMID- 24679052
TI  - Synthesis and in vitro biological evaluation of new heterocycles based on the
      indole moiety.
AB  - New compounds based on the indole moiety were synthesized via the reaction of
      indole-3-carbinal 1 with different nucleophiles such as 6-aryl-[4-(2
      methoxybenzyl)pyridazin-3-yl] hydrazones 2a-c, benzidine, 3,3'-dimethoxybenzidine
      4a,b and 2,6-diaminopyridine 6 to afford hydrazine derivatives 3a-c and three
      different classes of bis-Schiff bases. The structures of the new compounds were
      elucidated on the basis of their FTIR, (1)H NMR, (13)C NMR spectral data, GC/MS
      and elemental analysis. The antimicrobial activity of the new compounds was
      evaluated using a broth dilution technique in terms of minimal inhibitory
      concentration (MIC) against four pathogenic bacteria and two pathogenic fungi
      strains. Compound 14b showed excellent activity against Escherichia coli and
      Klebsiella pneumoniae. Some of the prepared compounds were tested for anti-cancer
      activity against human cell lines HCT116 (colon), MCF7 (breast) and HELA
      (cervix). From the results of the in vitro assays, compounds 3a,b, and 18a,c
      presented promising anti-cancer activity.

PMID- 24679053
TI  - "Interactive surfaces" technology as a potential tool to stimulate physical
      activity in psychogeriatric nursing home residents.
AB  - Abstract Purpose: The aims of this study were to determine whether and how
      psychogeriatric nursing home residents would respond to the interactive surfaces
      on the floor without receiving instructions and to determine how long residents
      would be physically active. Methods: The "interactive surfaces" technology
      includes different graphic shapes that are projected through a beamer on a floor.
      The surfaces are "activated" by a person's movements in the area of the
      projection field, which is detected by an infrared camera. Every day for 1 h
      during an 11-day period one of seven different projections was shown. Spontaneous
      observed physical responses were counted, clustered and visualized in a tree
      diagram. Duration of physically responses was measured per session and during the
      total observation period of 11 h. Results: During 343 of 490 observations
      residents (n = 58) noticed the interactive surface and in 148 observations they
      engaged physically. In total, 4067 s (1 h, 7 min and 47 s) of physical activity
      were measured. Individual times that residents were active ranged from 3 to 415
      s. Conclusions: Interactive surfaces technology may be a promising tool in
      psychogeriatric nursing home residents to stimulate physical activity. Further
      research is needed to assess its full potential. Implications for Rehabilitation
      Innovative technology used to adapt the environment might stimulate nursing home
      residents to become more physically active. The use of innovative technologies
      may increase physical activity without necessarily increasing the workload of
      care professionals.

PMID- 24679054
TI  - Cryofibrinogenemia After a Liver Transplant: First Reported Case Posttransplant
      and a Case-Based Review of the Nontransplant Literature.
AB  - Cryofibrinogenemia is a rare disorder in which plasma, not serum, forms a
      cryoprecipitate. Patients with cryofibrinogenemia may be asymptomatic, or they
      may have painful ulcers, purpura, livedo reticularis, Raynaud phenomenon,
      perniosis of the extremities, thrombosis, and arthralgia. Cryofibrinogenemia may
      be primary or secondary to an underlying disorder such as connective tissue
      disease, malignancy, infection, drugs, or thromboembolic disease. Here, we
      present a 41-year-old woman with a pancreatic neuroendocrine tumor who underwent
      a Whipple procedure in 2003 followed by 2 liver transplants for hepatic
      metastases. Three years posttransplant, we discovered a biopsy-proven metastatic
      lesion in her femur. Five years posttransplant, she developed acute, severe pain
      in both feet, and was found to have cryofibrinogenemia despite immunosuppression
      post-transplant. Testing for connective tissue diseases and hematologic
      malignancy were negative. She was treated with high-dose prednisone, which
      completely resolved her symptoms. We also conducted a review of the literature
      via a PubMed search to summarize the association of cryofibrinogenemia with
      malignancy and treating cryofibrinogenemia with corticosteroids. Our study is the
      first reported case of cryofibrinogenemia that developed secondary to a
      neuroendocrine tumor posttransplant. Our report suggests that cryofibrinogenemia
      may occur despite immunosuppression adequate to prevent graft rejection, and that
      high-dose corticosteroids are an effective treatment for posttransplant
      cryofibrinogenemia. 

PMID- 24679055
TI  - Skin of patients with large/giant congenital melanocytic nevi shows increased
      mast cells.
AB  - Nevocytes (NC) and mastocytes (MC) have different progenitors but share stem cell
      factor as regulator/activator of NC and for differentiation/proliferation of MC.
      Both cell types express stem cell factor receptor CD117. We hypothesize that
      large/giant congenital melanocytic nevi (L/GCMN) may associate with MC
      hyperplasia. Forty-nine L/GCMN were examined, 12 samples from uninvolved skin of
      L/GCMN patients and 6 control skin samples studied with Giemsa and
      immunohistochemistry for CD117 and MC-tryptase. Picrosirius red (PR) was used to
      assess fibrosis. Digital images were used to count MC/mm(2) using ImageJ
      software. Western blot (WB) for MC-tryptase in 12 GCMN and 12 non-nevus samples
      was performed. Analysis of variance (Tukey) and Pearson statistical tests were
      applied. Increased MCs were observed in nevus tissue (75.1 +/- 35.3 MCs/mm(2))
      and in uninvolved skin (53.74 +/- 27.7 MC/ mm(2)). P  =  0.109 from patients with
      L/GCMN, compared with controls from individuals without L/GCMN (28.74 +/- 8.4
      MC/mm(2)); P  =  0.001 supported by results of WB analysis for tryptase. A
      positive trend toward correlation of MC numbers with fibrosis, assessed by PR
      staining fell short of statistical significance (r  =  0.245; P  =  0.086); no
      difference in fibrosis was found between nevus and non-nevus skin from patients
      with L/GCMN (P  =  0.136). We found a higher density of MC, both in normal
      appearing skin and nevus areas of L/GCMN patients, compared with control skin
      samples from individuals without nevi. Given the abnormal wound healing and
      allergic reactions described in L/GCMN patients, these findings suggest a
      potential role for MC in the biology of L/GCMN, making them a potential target
      for therapeutic intervention.

PMID- 24679056
TI  - Oral gene therapy for hemophilia B using chitosan-formulated FIX mutants.
AB  - BACKGROUND: Oral gene delivery of non-viral vectors is an attractive strategy to
      achieve transgene expression. Although expected efficacy from non-viral delivery
      systems is relatively low, repeated vector administration is possible and may
      help to obtain durable transgene expression in a therapeutic range. OBJECTIVES:
      To test the principle feasibility of using factor (F) IX variants with improved
      function combined with an optimized oral delivery system in hemophilia B (HB)
      mice. METHODS: FIX modifications were introduced by site-directed mutagenesis
      into plasmid- or minicircle-based expression cassettes. Vectors were formulated
      as chitosan nanoparticles for oral delivery to HB mice. Protection of vector DNA
      in nanoparticle constructs and transfection efficiency were characterized. HB
      mice received eGFP-formulated chitosan nanoparticles to confirm gene transfer in
      vivo. FIX expression, phenotype correction and the potential of nanoparticles to
      induce immunotolerance (ITI) against exogenous FIX were evaluated after repeated
      oral administration. RESULTS: Transfection of HEK 293T cells or livers of FIX
      knockout mice with nanoparticles resulted in GFP or functional FIX expression.
      Oral administration of FIX mutants resulted in exclusive FIX expression in the
      small intestine, as confirmed by RT-PCR and fluorescence staining. HB mice
      demonstrated transient FIX expression reaching > 14% of normal activity and
      partial phenotype correction after oral delivery of FIX mutants with high
      specific activity and improved tissue release. CONCLUSION: The feasibility of
      oral, non-viral delivery of FIX was established and improved by bioengineered FIX
      proteins and optimized vectors. Thus, these data might point the way for
      development of a clinically applicable oral gene transfer strategy for hemophilia
      B.

PMID- 24679058
TI  - Three new flavonol glycosides from Suaeda maritima.
AB  - Three new flavonol glycosides isolated from the 70% methanol extract of Suaeda
      maritima (Chenopodiaceae) were characterized based on spectroscopic and chemical
      methods as quercetin 3-O-alpha-l-rhamnopyranosyl(1"' -> 6")-beta-d
      galactopyranoside-7-O-beta-d-glucopyranosyl(1""' -> 2"")-glucopyranoside,
      kaempferol 3-O-alpha-l-rhamnopyranosyl(1"' -> 6")-beta-d-galactopyranoside-7-O
      beta-d-glucopyranosyl(1""' -> 2"")-glucopyranoside, and kaempferol 3-O-alpha-l
      rhamnopyranosyl(1"' -> 6")-beta-d-galactopyranoside-7-O-(2""'-O-trans-feruloyl)
      beta-d-glucopyranosyl-(1""' -> 2"")-beta-d-glucopyranoside. In addition, four
      known compounds, namely, quercetin and kaempferol, methyl cis, trans-ferulate,
      and methyl trans-ferulate were identified. The plant extract and these compounds
      showed cytotoxic activity against the human tumor cell lines MCF7, HCT116, and
      HEPG2. 

PMID- 24679057
TI  - The selective cytotoxic anti-cancer properties and proteomic analysis of
      Trigonella Foenum-Graecum.
AB  - BACKGROUND: There are a number of dietary components that may prove useful in the
      prevention and treatment of cancer. In some cultures, fenugreek seeds are used to
      treat cancer. The current study focuses on the anticancer properties and
      proteomic profiles of fenugreek seeds, and is prompted by the clinical profile of
      a case of primary CNS T cell lymphoma that responded to fenugreek treatment and
      resulted in tumor regression. METHOD: Various normal and cancer cell lines were
      exposed to fenugreek extract at differing concentrations (100 MUg/ml, 200 MUg/ml
      and 300 MUg/ml) and at different time points (0, 24, 48, 72 and 96 hrs). Protein
      fingerprints of fenugreek grain/seed types, obtained from four different
      geographical regions, were analyzed by proteomic expression profiles. RESULTS: We
      observed selective cytotoxic effects of fenugreek extract in vitro to a panel of
      cancer cell lines, including T-cell lymphoma. Additionally, the cluster analysis
      of proteomics data showed that the protein profile of the particular fenugreek
      used by the patient is significantly different from three other regional subtypes
      of fenugreek extract. CONCLUSION: The in vitro effect of fenugreek as a substance
      with significant cytotoxicity to cancer cells points to the potential usefulness
      of fenugreek in the prevention and treatment of cancer.

PMID- 24679059
TI  - Collective asymmetric synthesis of (-)-antofine, (-)-cryptopleurine, (-)
      tylophorine, and (-)-tylocrebrine with tert-butanesulfinamide as a chiral
      auxiliary.
AB  - A collective asymmetric synthesis of phenanthroindolizidine and
      phenanthroquinolizidine alkaloids (-)-antofine, (-)-cryptopleurine, (-)
      tylophorine, and (-)-tylocrebrine was achieved by means of a reaction sequence
      involving efficient generation of chiral homoallylic amine intermediates by
      asymmetric allylation of the corresponding tert-butanesulfinyl imine. From these
      intermediates, the pyrrolidine and piperidine rings were constructed by means of
      an intramolecular SN2 substitution reaction and a ring-closing metathesis
      reaction, respectively. The unusual C5-methoxy-substituted phenanthrene moiety of
      (-)-tylocrebrine was generated by means of an InCl3-catalyzed cycloisomerization
      reaction of an o-propargylbiaryl compound.

PMID- 24679060
TI  - Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes.
AB  - BACKGROUND: In short-term randomized trials (duration, 1 to 2 years), bariatric
      surgery has been associated with improvement in type 2 diabetes mellitus.
      METHODS: We assessed outcomes 3 years after the randomization of 150 obese
      patients with uncontrolled type 2 diabetes to receive either intensive medical
      therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or
      sleeve gastrectomy. The primary end point was a glycated hemoglobin level of 6.0%
      or less. RESULTS: The mean (+/-SD) age of the patients at baseline was 48+/-8
      years, 68% were women, the mean baseline glycated hemoglobin level was 9.3+/
      1.5%, and the mean baseline body-mass index (the weight in kilograms divided by
      the square of the height in meters) was 36.0+/-3.5. A total of 91% of the
      patients completed 36 months of follow-up. At 3 years, the criterion for the
      primary end point was met by 5% of the patients in the medical-therapy group, as
      compared with 38% of those in the gastric-bypass group (P<0.001) and 24% of those
      in the sleeve-gastrectomy group (P=0.01). The use of glucose-lowering
      medications, including insulin, was lower in the surgical groups than in the
      medical-therapy group. Patients in the surgical groups had greater mean
      percentage reductions in weight from baseline, with reductions of 24.5+/-9.1% in
      the gastric-bypass group and 21.1+/-8.9% in the sleeve-gastrectomy group, as
      compared with a reduction of 4.2+/-8.3% in the medical-therapy group (P<0.001 for
      both comparisons). Quality-of-life measures were significantly better in the two
      surgical groups than in the medical-therapy group. There were no major late
      surgical complications. CONCLUSIONS: Among obese patients with uncontrolled type
      2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted
      in glycemic control in significantly more patients than did medical therapy
      alone. Analyses of secondary end points, including body weight, use of glucose
      lowering medications, and quality of life, also showed favorable results at 3
      years in the surgical groups, as compared with the group receiving medical
      therapy alone. (Funded by Ethicon and others; STAMPEDE ClinicalTrials.gov number,
      NCT00432809.).

PMID- 24679063
TI  - The yin and yang of perioperative medicine.

PMID- 24679064
TI  - Ethical pharmaceutical promotion and communications worldwide: codes and
      regulations.
AB  - The international pharmaceutical industry has made significant efforts towards
      ensuring compliant and ethical communication and interaction with physicians and
      patients. This article presents the current status of the worldwide governance of
      communication practices by pharmaceutical companies, concentrating on
      prescription-only medicines. It analyzes legislative, regulatory, and code-based
      compliance control mechanisms and highlights significant developments, including
      the 2006 and 2012 revisions of the International Federation of Pharmaceutical
      Manufacturers and Associations (IFPMA) Code of Practice.Developments in
      international controls, largely built upon long-established rules relating to the
      quality of advertising material, have contributed to clarifying the scope of
      acceptable company interactions with healthcare professionals. This article aims
      to provide policy makers, particularly in developing countries, with an overview
      of the evolution of mechanisms governing the communication practices, such as the
      distribution of promotional or scientific material and interactions with
      healthcare stakeholders, relating to prescription-only medicines. 

PMID- 24679065
TI  - Diagnostic yield of endoscopy in patients with abdominal complaints: incremental
      value of faecal calprotectin on guidelines of appropriateness.
AB  - BACKGROUND: European Panel on the Appropriateness of Gastrointestinal Endoscopy
      (EPAGE) criteria have been developed to increase diagnostic yield, but their
      predictive value is limited. We investigated the incremental diagnostic value of
      faecal calprotectin to EPAGE criteria. METHODS: In a post-hoc analysis of a
      prospective study, EPAGE criteria were applied to 298 of 575 (51.8%) patients who
      had undergone esophagogastroduodenoscopy (EGD), colonoscopy or both for abdominal
      complaints at the Division of Gastroenterology & Hepatology at the University
      Hospital Basel in Switzerland. Faecal calprotectin was measured in stool samples
      collected within 24 hours before the investigation using an enzyme-linked
      immunosorbent assay. Final endoscopic diagnoses were blinded to calprotectin
      values. RESULTS: Of 149 EGDs and 224 colonoscopies, 17.6% and 14.7% respectively
      were judged inappropriate by EPAGE criteria. Appropriate or uncertain indications
      revealed more endoscopic findings in both EGD (46.3% vs. 23.1%, P = 0.049) and
      colonoscopy (23.6% vs. 6.1%, P = 0.041) than inappropriate indications. Median
      calprotectin levels were higher (81.5 MUg/g, interquartile range 26-175, vs. 10
      MUg/g, IQR 10-22, P < 0.001) and testing was more often positive (>50 MUg/g) in
      patients with endoscopic findings, both in EGD (58.2% vs. 33.0%, P = 0.005) and
      in colonoscopy (57.3% vs. 7.4%, P < 0.001). The use of faecal calprotectin in
      addition to EPAGE criteria improved the risk reclassification of patients by
      endoscopic findings. The calculated net reclassification index was 37.8% (P =
      0.002) for EGD and 110.9% (P <0.001) for colonoscopy, thus improving diagnostic
      yield to 56.8% and 70.2%, respectively. CONCLUSIONS: The use of faecal
      calprotectin in addition to EPAGE criteria improved diagnostic yield in patients
      with abdominal complaints.

PMID- 24679066
TI  - Factors contributing to caregiver burden in dementia in a country without formal
      caregiver support.
AB  - OBJECTIVES: To investigate caregiver burden in dementia and explore factors
      associated with different types of burden in a country without formal caregiver
      support using a province in China as a case. METHOD: Cross-sectional
      questionnaire survey was used to collect data. One hundred and fifty-two family
      caregivers of people with dementia in community settings were recruited from 2012
      to 2013 using convenience sampling. Objective burden was measured by caregiving
      hours and dementia-related financial burden. Subjective burden was measured and
      analysed using the Caregiver Burden Inventory and the Neuropsychiatric Inventory
      Questionnaire. Multivariate regression models were employed to analyse factors
      associated with each type of subjective burden. RESULTS: Five types of subjective
      burden were measured by the Caregiver Burden Inventory, namely, physical burden,
      emotional burden, time-dependence burden, developmental burden, and social
      burden. Caregiver distress, as a subjective burden, was measured by the
      Neuropsychiatric Inventory-Questionnaire and reported by relating to the severity
      of care recipients' behavioural and psychological symptoms of dementia. This
      caregiver cohort showed a high level of physical, time-dependence, and
      developmental burdens, but a low level of emotional and social burdens. Factors
      contributing to each type of subjective burden measured by the Caregiver Burden
      Inventory differed from each other. CONCLUSION: The high level of objective and
      subjective burdens identified in this study suggests that government-funded
      formal caregiver support should be established and services should be designed to
      target different types of burdens and factors contributing to these burdens.

PMID- 24679067
TI  - Pattern and factors associated with congenital anomalies among young infants
      admitted at Bugando medical centre, Mwanza, Tanzania.
AB  - BACKGROUND: Congenital anomalies or birth defects are among the leading causes of
      infant mortality and morbidity around the world. The impact of congenital
      anomalies is particularly severe in middle- and low-income countries where health
      care resources are limited. The prevalence of congenital anomalies varies in
      different parts of the world, which could reflect different aetiological factors
      in different geographical regions. METHODS: Between October 2012 and January
      2013, a cross-sectional study was conducted involving young infants below 2
      months of age, admitted at a university teaching hospital in Tanzania. Face-to
      face interviews with parents/caretakers of young infants were carried out to
      collect socio-demographic and clinical information. Physical examinations were
      performed on all young infants. Echocardiography, X-ray, cranial as well as
      abdominal ultrasonographies were performed when indicated. RESULTS: Analysis of
      the data showed that among 445 young infants enrolled in the study, the
      prevalence of congenital anomalies was 29%, with the Central Nervous System (CNS)
      as the most commonly affected organ system. Maternal factors that were
      significantly associated with congenital anomalies included the lack of peri
      conceptional use of folic acid (OR = 3.1; 95% CI = 1.4-6.7; p = 0.005), a
      maternal age of above 35 years (OR = 2.2; 95% CI = 1.1-4.3; p = 0.024) and an
      inadequate attendance to antenatal clinic (OR = 2.1; 95% CI = 1.4-3.3; p <
      0.001). Infant factors that were significantly associated with congenital
      anomalies were female sex, a birth weight of 2.5 kg or more, singleton pregnancy
      and a birth order above 4. CONCLUSIONS: Due to the high prevalence of congenital
      anomalies observed in this particular context, the hospital should mobilize
      additional resources for an optimal and timely management of the patients with
      congenital anomalies. In this study, the proportion of women taking folic acid
      supplements during early pregnancy was very low. Efforts should be made to ensure
      that more women use folic acid during the peri-conceptional period, as the use of
      folic acid supplement has been linked by several authors to a reduced occurrence
      of some congenital anomalies.

PMID- 24679068
TI  - Impact of malaria related messages on insecticide-treated net (ITN) use for
      malaria prevention in Ghana.
AB  - BACKGROUND: Media messages have been used in Ghana to promote insecticide-treated
      net (ITN)/bed net usage in an effort to impact on malaria prevention. The aim of
      this study was to assess the effect of such malaria-related messages delivered
      through electronic/print media and by volunteers/health workers on the use of
      ITNs by children living in a household. METHODS: Data was collected from
      September to November of 2008 using a structured, interviewer-administered
      questionnaire by the Ghana Statistical Service as part of a national demographic
      and health survey (DHS). Secondary data analysis was performed on the collected
      data using multivariate logistic regression for both individual messages and a
      composite (any of) message variable. RESULTS: From the 11,788 households
      surveyed, 45% had at least one net. Households with male heads were more likely
      to have a child sleeping under a bed net the previous night (p = 0.0001).
      Individual Messages delivered by a health worker or a dedicated radio programme,
      had the highest effect for one or more children sleeping under a net the night
      before (OR(adjusted) = 1.65; 95% CI = 1.44 to 1.88 and OR(adjusted) = 1.26; 95%
      CI =1.12 to 1.42 respectively) while hearing any of the eight messages (composite
      score) resulted in the highest odds for one or more children (OR(adjusted) =
      3.06; 95% CI = 2.27 to 4.12) sleeping under a bed net. CONCLUSION: Efforts to
      relate ITN messages to the public are very useful in increasing use of bed nets
      and having multiple ways of reaching the public increases their effect, with the
      biggest effect seen when health workers and volunteers were used to deliver
      malaria-related messages to the public.

PMID- 24679062
TI  - Aspirin in patients undergoing noncardiac surgery.
AB  - BACKGROUND: There is substantial variability in the perioperative administration
      of aspirin in patients undergoing noncardiac surgery, both among patients who are
      already on an aspirin regimen and among those who are not. METHODS: Using a 2-by
      2 factorial trial design, we randomly assigned 10,010 patients who were preparing
      to undergo noncardiac surgery and were at risk for vascular complications to
      receive aspirin or placebo and clonidine or placebo. The results of the aspirin
      trial are reported here. The patients were stratified according to whether they
      had not been taking aspirin before the study (initiation stratum, with 5628
      patients) or they were already on an aspirin regimen (continuation stratum, with
      4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo
      just before surgery and continued it daily (at a dose of 100 mg) for 30 days in
      the initiation stratum and for 7 days in the continuation stratum, after which
      patients resumed their regular aspirin regimen. The primary outcome was a
      composite of death or nonfatal myocardial infarction at 30 days. RESULTS: The
      primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and
      in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin
      group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P=0.92). Major bleeding
      was more common in the aspirin group than in the placebo group (230 patients
      [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49;
      P=0.04). The primary and secondary outcome results were similar in the two
      aspirin strata. CONCLUSIONS: Administration of aspirin before surgery and
      throughout the early postsurgical period had no significant effect on the rate of
      a composite of death or nonfatal myocardial infarction but increased the risk of
      major bleeding. (Funded by the Canadian Institutes of Health Research and others;
      POISE-2 ClinicalTrials.gov number, NCT01082874.).

PMID- 24679061
TI  - Clonidine in patients undergoing noncardiac surgery.
AB  - BACKGROUND: Marked activation of the sympathetic nervous system occurs during and
      after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic
      outflow, may prevent perioperative myocardial infarction and death without
      inducing hemodynamic instability. METHODS: We performed a blinded, randomized
      trial with a 2-by-2 factorial design to allow separate evaluation of low-dose
      clonidine versus placebo and low-dose aspirin versus placebo in patients with, or
      at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A
      total of 10,010 patients at 135 centers in 23 countries were enrolled. For the
      comparison of clonidine with placebo, patients were randomly assigned to receive
      clonidine (0.2 mg per day) or placebo just before surgery, with the study drug
      continued until 72 hours after surgery. The primary outcome was a composite of
      death or nonfatal myocardial infarction at 30 days. RESULTS: Clonidine, as
      compared with placebo, did not reduce the number of primary-outcome events (367
      and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval
      [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients
      (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo
      (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients
      in the clonidine group than in the placebo group had clinically important
      hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32;
      95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was
      associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients]
      vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).
      CONCLUSIONS: Administration of low-dose clonidine in patients undergoing
      noncardiac surgery did not reduce the rate of the composite outcome of death or
      nonfatal myocardial infarction; it did, however, increase the risk of clinically
      important hypotension and nonfatal cardiac arrest. (Funded by the Canadian
      Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number,
      NCT01082874.).

PMID- 24679071
TI  - Protective effect of hydrogen sulfide on gentamicin-induced renal injury.
AB  - OBJECTIVE: We evaluated the potential protective effect of hydrogen sulfide (H2S)
      against GEN-induced nephrotoxicity in rats. MATERIALS AND METHODS: Twenty-four
      rats were randomly divided into four groups, each consisting of six animals as
      follows: (1) the rats were control, (2) intraperitoneally injected with GEN 14
      consecutive days (100 mg/kg/day), (3) treated with GEN plus %0.9 saline
      intraperitoneally for 14 days and (4) treated with GEN plus sodium hydrogen
      sulfide (NaHS)-exogenous H2S donor (56 umol/kg/day) for 14 days. After 15 days,
      rats were sacrificed and their kidneys were taken and blood analysis was
      performed. Twenty-four hours urine collections were obtained in standard
      metabolic cages a day before the rats were sacrificed. Tubular necrosis and
      interstitial fibrosis scoring were determined histopathologically in a part of
      kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH)
      levels were determined in the other part of kidneys. Statistical analyses were
      made by the chi-squared test and one-way analysis of variance. RESULTS: Serum
      urea and creatinine levels were significantly higher in rats treated with GEN
      alone, than the rats in control and GEN + NaHS groups. The GSH levels in renal
      tissue of only GEN-treated rats were significantly lower than those in control
      group, and administration of NaHS to GEN-treated rats significantly increased the
      level of GSH. The group that was given GEN and NaHS had significantly lower MDA
      and NO levels in kidney cortex tissue than those that was given GEN alone. In
      rats treated with GEN + NaHS, despite the presence of mild tubular degeneration
      and tubular necrosis are less severe, and glomeruli maintained a better
      morphology when compared with GEN group. DISCUSSION: We can say that H2S prevent
      kidney damage with antioxidant and anti-inflammatory effect.

PMID- 24679072
TI  - Structure-activity relationships in cytotoxic Au(I)/Au(III) complexes derived
      from 2-(2'-pyridyl)benzimidazole.
AB  - Gold(I) and gold(III) complexes derived from 2-(2'-pyridyl)benzimidazole (pbiH)
      were proven to be a promising class of in vitro antitumor agents against A2780
      human ovarian cancer cells. In this paper, a comparative electrochemical, UV-vis
      absorption, and emission spectroscopic investigation is reported on pbiH, the two
      mononuclear Au(III) complexes [(pbi)AuX2] (X = Cl (1), AcO (2)), the four
      mononuclear Au(I) derivatives [(pbiH)AuCl] (3), [(pbiH)Au(PPh3)]PF6 ((4(+))(PF6(
      ))), [(pbi)Au(PPh3)] (5), and [(pbi)Au(TPA)] (6), the three mixed-valence
      Au(III)/Au(I) complexes [(MU-pbi)Au2Cl3] (7), [(Ph3P)Au(MU-pbi)AuX2]PF6 (X = Cl
      ((8(+))(PF6(-))), AcO ((9(+))(PF6(-)))), and the binuclear Au(I)-Au(I) compound
      [(MU-pbi)Au2(PPh3)2]PF6 ((10(+))(PF6(-))). All complexes feature irreversible
      reduction processes related to the Au(III)/Au(I) or Au(I)/Au(0) processes and
      peculiar luminescent emission at about 360-370 nm in CH2Cl2, with quantum yields
      that are remarkably lower ((0.7-14.5) * 10(-2)) in comparison to that determined
      for the free pbiH ligand (31.5 * 10(-2)) in the same solvent. The spectroscopic
      and electrochemical properties of all complexes were interpreted on the grounds
      of time-dependent PBE0/DFT calculations carried out both in the gas phase and in
      CH2Cl2 implicitly considered within the IEF-PCM SCRF approach. The electronic
      structure of the complexes, and in particular the energy and composition of the
      Kohn-Sham LUMOs, can be related to the antiproliferative properties against the
      A2780 ovarian carcinoma cell line, providing sound quantitative structure
      activity relationships and shedding a light on the role played by the global
      charge and nature of ancillary ligands in the effectiveness of Au-based antitumor
      drugs. 

PMID- 24679070
TI  - Secondary structure in the core of amyloid fibrils formed from human beta2m and
      its truncated variant DeltaN6.
AB  - Amyloid fibrils formed from initially soluble proteins with diverse sequences are
      associated with an array of human diseases. In the human disorder, dialysis
      related amyloidosis (DRA), fibrils contain two major constituents, full-length
      human beta2-microglobulin (hbeta2m) and a truncation variant, DeltaN6 which lacks
      the N-terminal six amino acids. These fibrils are assembled from initially
      natively folded proteins with an all antiparallel beta-stranded structure. Here,
      backbone conformations of wild-type hbeta2m and DeltaN6 in their amyloid forms
      have been determined using a combination of dilute isotopic labeling strategies
      and multidimensional magic angle spinning (MAS) NMR techniques at high magnetic
      fields, providing valuable structural information at the atomic-level about the
      fibril architecture. The secondary structures of both fibril types, determined by
      the assignment of ~80% of the backbone resonances of these 100- and 94-residue
      proteins, respectively, reveal substantial backbone rearrangement compared with
      the location of beta-strands in their native immunoglobulin folds. The
      identification of seven beta-strands in hbeta2m fibrils indicates that
      approximately 70 residues are in a beta-strand conformation in the fibril core.
      By contrast, nine beta-strands comprise the fibrils formed from DeltaN6,
      indicating a more extensive core. The precise location and length of beta-strands
      in the two fibril forms also differ. The results indicate fibrils of DeltaN6 and
      hbeta2m have an extensive core architecture involving the majority of residues in
      the polypeptide sequence. The common elements of the backbone structure of the
      two proteins likely facilitates their ability to copolymerize during amyloid
      fibril assembly.

PMID- 24679073
TI  - Overexpression of lactate dehydrogenase-A in human intrahepatic
      cholangiocarcinoma: its implication for treatment.
AB  - BACKGROUND: Previous studies have shown that lactate dehydrogenase-A (LDH-A) is
      strongly expressed in several malignancies, that LDH-A expression is associated
      with poor prognosis, and that LDH-A inhibition severely diminishes
      tumorigenicity. However, little is known about the implications of LDH-A
      expression in intrahepatic cholangiocarcinoma. The purpose of this study was to
      investigate the expression of LDH-A and to clarify its effect on intrahepatic
      cholangiocarcinoma. METHODS: We studied the expression of LDH-A in tissue samples
      from patients with intrahepatic cholangiocarcinoma (n = 54) using the
      ultrasensitive surfactant protein (S-P) immunohistochemical method. We then
      inhibited LDH-A using small hairpin RNA (shRNA) in the cholangiocarcinoma cell
      line HuCCT-1 in vitro to study the role it plays in promoting growth and escaping
      apoptosis. RESULTS: We report that LDH-A was overexpressed in 52 of 54 (96%)
      paraffin-embedded cancer tissue samples and 0 of 54 para-carcinoma tissue
      samples. Reduction of LDH-A by RNA interference (RNAi) inhibited cell growth and
      induced apoptosis in HuCCT-1 cells. This result correlated with the elevation of
      cytoplasmic reactive oxygen species (ROS) levels. CONCLUSIONS: LDH-A expression
      is closely correlated with histopathological variables of intrahepatic
      cholangiocarcinoma, indicating that LDH-A may serve as a new treatment target.

PMID- 24679074
TI  - Feasibility study of the BrightBrainerTM integrative cognitive rehabilitation
      system for elderly with dementia.
AB  - PURPOSE: To describe the development of BrightBrainerTM integrative cognitive
      rehabilitation system and determine clinical feasibility with nursing home-bound
      dementia patients. METHOD: BrightBrainer cognitive rehabilitation simulations
      were first played uni-manually, then bimanually. Participants sat in front of a
      laptop and interacted through a game controller that measured hand movements in
      3D, as well as flexion of both index fingers. Interactive serious games were
      designed to improve basic and complex attention (concentration, short-term
      memory, dual tasking), memory recall, executive functioning and emotional well
      being. Individual simulations adapted automatically to each participant's level
      of motor functioning. The system underwent feasibility trials spanning 16
      sessions over 8 weeks. Participants were evaluated pre- and post-intervention,
      using standardized neuropsychological measures. Computerized measures of movement
      repetitions and task performance were stored on a remote server. RESULTS: Group
      analysis for 10 participants showed statistically significant improvement in
      decision making (p < 0.01), with trend improvements in depression (p < 0.056).
      Improvements were also seen in processing speed (p < 0.13) and auditory attention
      (p < 0.17); however, these were not statistically significant (partly
      attributable to the modest sample size). Eight of nine neuropsychological tests
      showed changes in the improvement direction indicating an effective
      rehabilitation (p < 0.01). BrightBrainer technology was well tolerated with mean
      satisfaction ratings of 4.9/5.0 across participants. CONCLUSIONS: Preliminary
      findings demonstrate utility within an advanced dementia population, suggesting
      that it will be beneficial to evaluate BrightBrainer through controlled clinical
      trials and to investigate its application in other clinical populations.
      Implications for Rehabilitation It is possible to improve cognitive function in
      older low-functioning patients. Integrative rehabilitation through games
      combining cognitive (memory, focusing, executive function) and physical (bimanual
      whole arm movement, grasping, task sequencing) elements is enjoyable for this
      population. The severity of depression in these elderly can be reduced through
      virtual reality bimanual games. The number of upper extremity active repetitions
      performed in the process of solving cognitive problems with the BrightBrainerTM
      system is 600. This number is 18 times (1875%) larger than those observed by
      other researchers in conventional physical or occupational rehabilitation
      sessions.

PMID- 24679075
TI  - Development of acute pancreatitis caused by sodium valproate in a patient with
      bipolar disorder on hemodialysis for chronic renal failure: a case report.
AB  - BACKGROUND: Cases of acute pancreatitis caused by sodium valproate (VPA) have
      been reported by many authors thus far. However, most of these were cases with
      epilepsy. Chronic renal failure is also regarded as a risk factor for acute
      pancreatitis. Here, we report a case of acute pancreatitis development due to VPA
      in a patient with bipolar disorder on hemodialysis for chronic renal failure.
      CASE PRESENTATION: The patient was a 52-year-old Japanese male who was diagnosed
      as bipolar disorder on hemodialysis for renal failure. He was treated with VPA
      and manic symptoms gradually stabilized. However, the patient complained of
      severe abdominal pain. Blood amylase was found to be markedly high, and computed
      tomography revealed pancreatomegaly and an increased amount of peripancreatic
      fat. Hence, we diagnosed the case as acute pancreatitis caused by VPA. We
      discontinued oral medication, and he was started on a pancreatic enzyme
      inhibitor, antibiotics, and transfusion, and he showed improvement. CONCLUSION:
      It has been reported that acute pancreatitis induced by VPA is caused by
      intermediate metabolites of VPA. We consider that patients with renal failure are
      prone to pancreatitis caused by VPA because of the accumulation of these
      intermediate metabolites. We need close monitoring for serious adverse effects
      such as pancreatitis when we prescribe VPA to patients with bipolar disorder on
      hemodialysis for chronic renal failure, although VPA is safer than other mood
      stabilizers.

PMID- 24679069
TI  - Sublingual immunotherapy: World Allergy Organization position paper 2013 update.
AB  - We have prepared this document, "Sublingual Immunotherapy: World Allergy
      Organization Position Paper 2013 Update", according to the evidence-based
      criteria, revising and updating chapters of the originally published paper,
      "Sublingual Immunotherapy: World Allergy Organization Position Paper 2009",
      available at http://www.waojournal.org. Namely, these comprise: "Mechanisms of
      sublingual immunotherapy;" "Clinical efficacy of sublingual immunotherapy" -
      reporting all the data of all controlled trials published after 2009; "Safety of
      sublingual immunotherapy" - with the recently published Grading System for
      adverse reactions; "Impact of sublingual immunotherapy on the natural history of
      respiratory allergy" - with the relevant evidences published since 2009;
      "Efficacy of SLIT in children" - with detailed analysis of all the studies;
      "Definition of SLIT patient selection" - reporting the criteria for eligibility
      to sublingual immunotherapy; "The future of immunotherapy in the community care
      setting"; "Methodology of clinical trials according to the current scientific and
      regulatory standards"; and "Guideline development: from evidence-based medicine
      to patients' views" - including the evolution of the methods to make clinical
      recommendations.Additionally, we have added new chapters to cover a few emerging
      crucial topics: "Practical aspects of schedules and dosages and counseling for
      adherence" - which is crucial in clinical practice for all treatments;
      "Perspectives and new approaches" - including recombinant allergens, adjuvants,
      modified allergens, and the concept of validity of the single products.
      Furthermore, "Raising public awareness about sublingual immunotherapy", as a need
      for our patients, and strategies to increase awareness of allergen immunotherapy
      (AIT) among patients, the medical community, all healthcare stakeholders, and
      public opinion, are also reported in detail. 

PMID- 24679076
TI  - Integrative network analysis of the signaling cascades in seedling leaves of
      bread wheat by large-scale phosphoproteomic profiling.
AB  - Here, we conducted the first large-scale leaf phosphoproteome analysis of two
      bread wheat cultivars by liquid chromatography-tandem mass spectrometry.
      Altogether, 1802 unambiguous phosphorylation sites representing 1175
      phosphoproteins implicated in various molecular functions and cellular processes
      were identified by gene ontology enrichment analysis. Among the 1175
      phosphoproteins, 141 contained 3-10 phosphorylation sites. The phosphorylation
      sites were located more frequently in the N- and C-terminal regions than in
      internal regions, and ~70% were located outside the conserved regions.
      Conservation analysis showed that 90.5% of the phosphoproteins had phosphorylated
      orthologs in other plant species. Eighteen significantly enriched phosphorylation
      motifs, of which six were new wheat phosphorylation motifs, were identified. In
      particular, 52 phosphorylated transcription factors (TFs), 85 protein kinases
      (PKs), and 16 protein phosphatases (PPs) were classified and analyzed in depth.
      All the Tyr phosphorylation sites were in PKs such as mitogen-activated PKs
      (MAPKs) and SHAGGY-like kinases. A complicated cross-talk phosphorylation
      regulatory network based on PKs such as Snf1-related kinases (SnRKs), calcium
      dependent PKs (CDPKs), and glycogen synthase kinase 3 (GSK3) and PPs including
      PP2C, PP2A, and BRI1 suppressor 1 (BSU1)-like protein (BSL) was constructed and
      was found to be potentially involved in rapid leaf growth. Our results provide a
      series of phosphoproteins and phosphorylation sites in addition to a potential
      network of phosphorylation signaling cascades in wheat seedling leaves. 

PMID- 24679077
TI  - Evolution of hollow TiO2 nanostructures via the Kirkendall effect driven by
      cation exchange with enhanced photoelectrochemical performance.
AB  - Hollow nanostructures are promising building blocks for electrode scaffolds and
      catalyst carriers in energy-related systems. In this paper, we report a discovery
      of hollow TiO2 nanostructure evolution in a vapor-solid deposition system. By
      introducing TiCl4 vapor pulses to ZnO nanowire templates, we obtained TiO2
      tubular nanostructures with well-preserved dimensions and morphology. This
      process involved the cation exchange reaction between TiCl4 vapor and ZnO solid
      and the diffusion of reactants and products in their vapor or solid phases, which
      was likely a manifestation of the Kirkendall effect. The characteristic
      morphologies and the evolution phenomena of the hollow nanostructures from this
      vapor-solid system were in a good agreement with the Kirkendall effect discovered
      in solution systems. Complex hollow TiO2 nanostructures were successfully
      acquired by replicating various ZnO nanomorphologies, suggesting that this unique
      cation exchange process could also be a versatile tool for nanostructure
      replication in vapor-solid growth systems. The evolution of TiO2 nanotubes from
      ZnO NW scaffolds was seamlessly integrated with TiO2 NR branch growth and thus
      realized a pure TiO2-phased 3D NW architecture. Because of the significantly
      enlarged surface area and the trace amount of Zn left in the TiO2 crystals, such
      3D TiO2 nanoforests demonstrated enhanced photoelectrochemical performance
      particularly under AM (air mass) 1.5G illumination, offering a new route for
      hierarchical functional nanomaterial assembly and application. 

PMID- 24679078
TI  - Preoperative neuropsychological and behavioral evaluation of children with
      thalamic tumors.
AB  - OBJECT: Functional involvement of the thalamus in cognitive processing has been
      only anecdotally reported in the literature, and these cases are mostly related
      to thalamic hemorrhages; there is no available information on cognitive
      development in children with thalamic tumors. METHODS: All children admitted with
      a diagnosis of thalamic tumor at the authors' institution between January 2008
      and January 2011 were considered for the present study. Exclusion criteria were
      age less than 18 months and the presence of severe neurological deficits, both of
      which prevented a reliable neuropsychological evaluation. A complete preoperative
      neuropsychological evaluation was performed. RESULTS: Twenty children were
      selected (mean age 102.4 months). Total IQ was in the normal range in all
      patients (mean 90.1, SD 13.87) with a significant difference between verbal IQ
      (mean 97.70, SD 17.77) and performance IQ (mean 84.82, SD 17.01). A significant
      correlation was found between global cognitive impairment and a histological
      finding of low-grade tumors (p < 0.001). Children with a mesial thalamic tumor
      had a higher working memory deficit and delayed recall disorders (p < 0.001).
      Naming disorders were related to the presence of a bilateral (p < 0.001) or
      mesial (p < 0.001) thalamic tumor, without a significant difference between left
      or right hemisphere involvement. A significant correlation was also found between
      the presence of neurolinguistic disorders and mesially located tumors (p <
      0.001). Children with right-sided tumors more frequently had constructional
      apraxia and executive function disorders (p < 0.001). CONCLUSIONS: The present
      study suggests that thalamic tumors in different locations might have specific
      neuropsychological profiles.

PMID- 24679079
TI  - Isolated unilateral rupture of the alar ligament.
AB  - Only 6 cases of isolated unilateral rupture of the alar ligament have been
      previously reported. The authors report a new case and review the literature,
      morbid anatomy, and pathogenesis of this rare injury. The patient in their case,
      a 9-year-old girl, fell head first from a height of 5 feet off the ground. She
      presented with neck pain, a leftward head tilt, and severe limitation of right
      rotation, extension, and right lateral flexion of the neck. Plain radiographs and
      CT revealed no fracture but a shift of the dens toward the right lateral mass of
      C-1. Magnetic resonance imaging of the cervical spine showed signal
      hyperintensity within the left dens-atlas space on both T1- and T2-weighted
      sequences and interruption of the expected dark signal representing the left alar
      ligament, suggestive of its rupture. After 12 weeks of immobilization in a
      Guilford brace, MRI showed lessened dens deviation, and the patient attained full
      and painless neck motion. Including the patient in this case, the 7 patients with
      this injury were between 5 and 21 years old, sustained the injury in traffic
      accidents or falls, presented with marked neck pain, and were treated with
      external immobilization. All patients had good clinical outcome. The mechanism of
      injury is hyperflexion with rotation. Isolated unilateral alar ligament rupture
      is a diagnosis made by excluding associated fracture, dislocation, or disruption
      of other major ligamentous structures in the craniovertebral junction. CT and MRI
      are essential in establishing the diagnosis. External immobilization is adequate
      treatment. 

PMID- 24679080
TI  - Spontaneous improvement in urological dysfunction in children with congenital
      spinal lipomas of the conus medullaris.
AB  - Congenital spinal lipomas of the conus (SLCs) are among the most common closed
      neural tube defects. The treatment of SLC is an area of controversy because the
      true natural history of this condition is unknown. Here, the authors present two
      cases of SLC presenting in infancy with compromised lower urinary tract function,
      which was objectively confirmed by abnormal urodynamic studies. In both cases,
      there was spontaneous improvement in urodynamic parameters, with stable normal
      urinary function at the long-term follow-up. Although cases of spontaneous
      radiological regression of SLC have very infrequently been reported, they have
      not been associated with the reversal of already present neurological deficits.
      This report reinforces the need for further delineation of the true natural
      history of SLC and highlights the dynamic nature of associated neurological
      compromise over time. 

PMID- 24679081
TI  - Surgical management of pediatric brainstem cavernous malformations.
AB  - OBJECT: The goal of this study was to evaluate surgical outcomes of pediatric
      brainstem cavernous malformations (CMs) and identify the risk factors associated
      with postoperative full recovery and rebleeding. METHODS: The clinical charts and
      radiographs from a series of 52 pediatric patients (37 male and 15 female; mean
      age 12.2 years; range 1-17 years) who underwent surgery for brainstem CMs between
      1996 and 2011 were reviewed. Follow-up evaluation measures were obtained
      retrospectively. Neurological function was evaluated using the modified Rankin
      Scale (mRS) score. RESULTS: The lesion locations among the 52 patients included
      the midbrain (n = 7, 13.5%), pons (n = 38, 73.1%), and medulla (n = 7, 13.5%).
      The mean duration of symptoms was 18.5 months, and the preoperative annual
      hemorrhage and rebleeding rates were 12.3% and 32.5% per patient-year,
      respectively. The mean lesion size was 2.1 cm. Gross-total resection without
      surgery-related death was achieved in 49 patients (94.2%). Immediate
      postoperative reduced neurological function was observed in 17 patients (32.7%).
      Surgical morbidities developed in 25 patients (48.1%) and remained in 11 patients
      (21.2%) after 7.9 years of follow-up. The mean mRS scores at admission, discharge
      after surgery, 3 and 6 months postsurgery, and recent evaluation were 2.0, 2.3,
      2.0, 1.5, and 1.0, respectively. The postoperative mRS scores at 6 months (p <
      0.001) and on recent evaluation (p < 0.001) were significantly lower than those
      at admission. Postoperative rebleeding occurred in 2 patients, and the
      postoperative annual rebleeding rate was 0.5% per patient-year. By the most
      recent evaluation, 10 patients (19.2%) had achieved full recovery and all
      patients were either improved (n = 32, 61.5%) or unchanged (n = 20, 38.5%). The
      adverse predictors for full recovery included age >= 12 years (HR 0.230, p =
      0.021), >= 2 preoperative hemorrhages (HR 0.124, p = 0.048), and poor
      preoperative status (HR 0.197, p = 0.040). An HR < 1 predicted poor complete
      recoveries. The single risk factor predicting postoperative rebleeding was
      incomplete resection (chi2 = 4.340, p = 0.037). CONCLUSIONS: Fair outcomes for
      pediatric brainstem CMs could be obtained through surgery, but only a few
      patients achieved full recovery. Thus, to minimize surgical morbidity, surgical
      planning must be tailored to individual patients in all cases in which an
      operation is warranted. Complete resection must be attempted to reduce the risk
      of postoperative rebleeding. The predictors associated with complete
      postoperative recovery were referential for determining treatment.

PMID- 24679082
TI  - Thermodynamic properties of chloramine formation and related reactions during
      water treatment: a G4MP2, G4, and W1BD theoretical study.
AB  - A high-level gas and aqueous phase theoretical thermodynamic study was conducted
      on the primary and related chemical reactions which occur during chloramination
      for water treatment using the G4MP2, G4, and W1BD composite methods with the SMD,
      PCM, and CPCM solvation models. The standard state (298.15 K, 1 atm or 1M)
      formation of mono-, di-, and tri-chloramines from their precursors via
      hypochlorous acid chlorination is substantially exothermic and exergonic in both
      the gas and aqueous phases. The excellent agreement between experimental and
      theoretical values for a range of structural and thermodynamic calculations on a
      suite of calibration compounds suggests that the G4MP2, G4, and W1BD calculations
      meet or exceed criteria for thermochemical accuracy. The temperature influence on
      the thermodynamics of chloramine formation is projected to be negligible
      regardless of phase between 0 and 100 degrees C. Additional thermodynamic
      calculations were undertaken on associated chloramination reactions involving the
      disproportionation of monochloramine, the decomposition of di- and tri
      chloramine, and the reactions of trichloramine with ammonia and dichloramine. The
      results from these investigations not only provide a better understanding of the
      reaction thermodynamics, they also allow for a more rigorous interpretation of
      proposed chloramination mechanisms. 

PMID- 24679084
TI  - Comparison study on observed and estimated concentrations of perfluorooctane
      sulfonate using a fate model in Tokyo Bay of Japan.
AB  - Perfluorooctane sulfonate (PFOS) was quantified in seawater and sediment samples
      collected from Tokyo Bay, Japan, ranging from 2.0 to 7.3 ng/L for surface
      seawater, 2.2 to 5.7 ng/L for intermediate seawater, 1.5 to 5.7 ng/L for bottom
      seawater, and 0.3 to 0.9 ng/g dry wt. for sediment. In addition, a 3-D chemical
      fate prediction model (National Institute of Advanced Industrial Science and
      Technology - Risk Assessment Model: AIST-RAM) has been applied to determine the
      accuracy of estimating PFOS in Tokyo Bay. A decreasing trend of PFOS from the
      northwestern part (i.e., the closed-off section of Tokyo Bay) to the mouth of the
      bay was observed, and the trend obtained from the actual surveys in this study
      was accurately represented by simulation with appropriate input parameters for
      AIST-RAM. From the comparison of observed concentrations with estimated
      concentrations, AIST-RAM showed a high degree of accuracy in estimating the
      concentrations of PFOS in seawater, whereas the estimations of PFOS
      concentrations in sediment had a relatively larger margin of error than those in
      seawater. However, our results indicate that AIST-RAM allows estimation of PFOS
      concentrations in seawater and sediment in Tokyo Bay with satisfactory accuracy.

PMID- 24679083
TI  - Preparation of iron oxide-impregnated spherical granular activated carbon-carbon
      composite and its photocatalytic removal of methylene blue in the presence of
      oxalic acid.
AB  - The spherical granular activated carbon-carbon composites (GAC-Fe) with different
      iron oxide contents (Fe mass% = 0.6-10) were prepared by a pore volume
      impregnation method. The X-ray diffraction (XRD), scanning electron microscopy
      (SEM), and N2-adsorption results confirm the presence of amorphous iron oxide,
      pyrolytic carbon, and graphitized globular carbon nanoparticles covered with
      amorphous carbon in the CAG-Fe. The rate of photodegradation of methylene blue
      (MB) in aqueous solution under UV light in the presence of oxalic acid correlates
      with porosity of the prepared materials. The total MB removal includes the
      combination of adsorption and photodegradation without the addition of H2O2. The
      results of total organic carbon (TOC) analysis reveal that the decolorization of
      MB in aqueous solution containing oxalic acid corresponds to the decomposition of
      organic compounds to CO2 and H2O. 

PMID- 24679085
TI  - Transformation of iso-pentylbenzene by a biofilm-forming strain of Candida
      viswanathii TH1 isolated from oil-polluted sediments collected in coastal zones
      in Vietnam.
AB  - This work is aimed to assess the aerobic biotransformation of a branched side
      chain alkylbenzene, iso-pentylbenzene, by Candida viswanathii TH1. The yeast
      Candida viswanathii TH1 isolated from oil-polluted sediments collected in coastal
      zones in Vietnam exhibited as a strain that could better transform branched
      aromatic hydrocarbons in biofilm (pellicle) than in planktonic form. During
      incubation of TH1 as biofilm with iso-pentylbenzene, the seven intermediates
      produced were benzoic acid, phenylacetic acid, 2-methyl-4-phenyl-butan-1-ol, 2
      hydroxy-phenylacetic acid, 2-methyl-4-phenylbutyric acid, succinic acid and iso
      valerophenone as revealed by gas chromatography/mass spectra and high-performance
      liquid chromatography analyses. The occurrence of these intermediates showed that
      iso-pentylbenzene could be oxidized not only via mono- but also by a sub-terminal
      oxidation pathway. This is the first study on iso-pentylbenzene transformation by
      a biofilm-forming Candida viswanathii strain. The catabolic versatility of the
      biofilm-forming strain TH1 and its use for mono and sub-terminal oxidation during
      the transformation of iso-pentylbenzene enhance our understanding of the
      degradation of branched side chain phenylalkanes and give new insight into the
      potential role of such species in the transformation of other recalcitrant
      aromatic compounds. 

PMID- 24679086
TI  - Health effects and arsenic species in urine of copper smelter workers.
AB  - The aim of this study was to compare indices of exposure in workers employed at
      different work posts in a copper smelter plant using neurophysiological tests and
      to evaluate the relationship between urinary arsenic species with the aid of
      sensitive respiratory and renal biomarkers. We have attempted to elucidate the
      impact of different arsenic speciation forms on the observed health effects. We
      focused on the workers (n = 45) exposed to atmospheres containing specific
      diverse mixtures of metals (such as those occurring in Departments of Furnaces,
      Lead and Electrolysis) compared to controls (n = 16). Subjective symptoms from
      the central (CNS) and the peripheral (PNS) nervous system were recorded and
      visual evoked potential (VEP), electroneurography (ENeG) and
      electroencephalography (EEG) curves were analysed. Levels of airborne lead (PbA),
      zinc (ZnA) and copper (CuA) and Pb levels in blood (PbB) and the relationships
      between airborne As concentrations (AsA) and the urinary levels of the inorganic
      (iAs); As(+3), As(+5) and the organic; methylarsonate (MMA(V)), dimethylarsinate
      (DMA(V)) and arsenobetaine (AsB) arsenic species were determined by Inductively
      Coupled Plasma Mass Spectrometry (ICP-MS). Effects of exposure were expressed in
      terms of biomarker levels: Clara cell protein (CC16) in serum as early pulmonary
      biomarker and beta2-microglobulin (beta2M) in urine and serum, retinol binding
      protein (RBP) as renal markers, measured by sensitive latex-immunoassay (LIA).
      Abnormal results of neurophysiological tests, VEP, EEG and ENeG showed dominant
      subclinical effects in CNS and PNS of workers from Departments of Lead and
      Furnace. In group of smelters from Departments of Furnace exposed to arsenic
      above current TLV, excreted arsenic species As(+3) and As(+5) seemed to reduce
      the level of Clara cell protein (CC16), thereby reducing anti-inflammatory
      potential of the lungs and increasing the levels of renal biomarker (beta2M) and
      copper in urine (CuU). The study confirmed deleterious arsenic effects to the
      kidney by increased levels of low-molecular weight protein in urine and the
      extent of the renal copper accumulation/excretion. The results of our work also
      support the usefulness of application of the sensitive neurophysiologic tests,
      such as VEP, EEG and ENeG, for the detection of early subclinical effects of the
      exposure of the nervous system in copper smelters. 

PMID- 24679087
TI  - Selective Hg(II) adsorption from aqueous solutions of Hg(II) and Pb(II) by
      hydrolyzed acrylamide-grafted PET films.
AB  - Selective Hg(II) adsorption from aqueous solutions of Hg(II) and Pb(II) using
      hydrolyzed acrylamide (AAm)-grafted polyethylene terephthalate (PET) films was
      examined to explore the potential reuse of waste PET materials. Selective
      recovery of Hg(II) from a mixture of soft acids with similar structure, such as
      Hg(II) and Pb(II), is important to allow the reuse of recovered Hg(II). An
      adsorbent for selective Hg(II) adsorption was prepared by gamma-ray-induced
      grafting of AAm onto PET films followed by partial hydrolysis through KOH
      treatment. The adsorption capacity of the AAm-grafted PET films for Hg(II) ions
      increased from 15 to 70 mg/g after partial hydrolysis because of the reduction of
      hydrogen bonding between -CONH2 groups and the corresponding improved access of
      metal ions to the amide groups. The prepared adsorbent was characterized by
      Fourier transform infrared spectroscopy and scanning electron microscopy. The
      absorbent film showed high selectivity for the adsorption of Hg(II) over Pb(II)
      throughout the entire initial metal concentration range (100-500 mg/L) and pH
      range (2.2-5.6) studied. The high selectivity is attributed to the ability of
      Hg(II) ions to form covalent bonds with the amide groups. The calculated
      selectivity coefficient for the adsorbent binding Hg(II) over Pb(II) was 19.2 at
      pH 4.5 with an initial metal concentration of 100 mg/L. Selective Hg(II)
      adsorption equilibrium data followed the Langmuir model and kinetic data were
      well fitted by a pseudo-second-order equation. The adsorbed Hg(II) and Pb(II)
      ions were effectively desorbed from the adsorbent film by acid treatment, and the
      regenerated film showed no marked loss of adsorption capacity upon reuse for
      selective Hg(II) adsorption.

PMID- 24679089
TI  - Characteristics of bacterial and fungal growth in plastic bottled beverages under
      a consuming condition model.
AB  - Microbial contamination in unfinished beverages can occur when drinking directly
      from the bottle. Various microorganisms, including foodborne pathogens, are able
      to grow in these beverages at room temperature or in a refrigerator. In this
      study, we elucidated the characteristics of microorganism growth in bottled
      beverages under consuming condition models. Furthermore, we provide insight into
      the safety of partially consumed bottled beverages with respect to food hygiene.
      We inoculated microorganisms, including foodborne pathogens, into various plastic
      bottled beverages and analysed the dynamic growth of microorganisms as well as
      bacterial toxin production in the beverages. Eight bottled beverage types were
      tested in this study, namely green tea, apple juice drink, tomato juice,
      carbonated drink, sport drink, coffee with milk, isotonic water and mineral
      water, and in these beverages several microorganism types were used: nine
      bacteria including three toxin producers, three yeasts, and five moulds.
      Following inoculation, the bottles were incubated at 35 degrees C for 48 h for
      bacteria, 25 degrees C for 48 h for yeasts, and 25 degrees C for 28 days for
      moulds. During the incubation period, the number of bacteria and yeasts and
      visible changes in mould-growth were determined over time. Our results indicated
      that combinations of the beverage types and microorganism species correlated with
      the degree of growth. Regarding factors that affect the growth and toxin
      productivity of microorganisms in beverages, it is speculated that the pH,
      static/shaking culture, temperature, additives, or ingredients, such as carbon
      dioxide or organic matter (especially of plant origin), may be important for
      microorganism growth in beverages. Our results suggest that various types of
      unfinished beverages have microorganism growth and can include food borne
      pathogens and bacterial toxins. Therefore, our results indicate that in terms of
      food hygiene it is necessary to consume beverages immediately after opening the
      bottle.

PMID- 24679088
TI  - Bioleaching of metals from spent refinery petroleum catalyst using moderately
      thermophilic bacteria: effect of particle size.
AB  - The present work investigated the leaching potential of moderately thermophilic
      bacteria in the recovery of metals from spent petroleum catalyst of varying
      particle sizes. The batch bioleaching experiments were conducted by employing a
      mixed consortium of moderate thermophilic bacteria at 45 degrees C and by using
      five different particle sizes (from 45 to >2000 MUm) of acetone-washed spent
      catalyst. The elemental mapping by FESEM confirmed the presence of Al, Ni, V and
      Mo along with sulfur in the spent catalyst. During bioleaching, Ni (92-97%) and V
      (81-91%) were leached in higher concentrations, whereas leaching yields of Al (23
      38%) were found to be lowest in all particle sizes investigated. Decreasing the
      particle size from >2000 MUm to 45-106 MUm caused an increase in leaching yields
      of metals during initial hours. However, the final metals leaching yields were
      almost independent of particle sizes of catalyst. Leaching kinetics was observed
      to follow the diffusion-controlled model showing the linearity more close than
      the chemical control. The results of the present study suggested that bioleaching
      using moderate thermophilic bacteria was highly effective in removing the metals
      from spent catalyst. Moreover, bioleaching can be conducted using spent catalyst
      of higher particle size (>2000 MUm), thus saving the grinding cost and making
      process attractive for larger scale application.

PMID- 24679090
TI  - The evaluation of heavy metal content in water and sediments of small reservoirs
      in light of various environmental quality regulations.
AB  - This article reports the heavy metal concentrations assessed both in bottom
      sediments and water flowing into two small reservoirs at Krempna and Zeslawice,
      southern Poland. The experiments were carried out in spring, summer, autumn and
      winter 2010-2011. The resulting concentrations of lead, cadmium, nickel, chromium
      and copper were compared with the Environmental Quality Standards, guidelines of
      the Regulation of the Minister of Environmental Protection, regulations of the
      Polish Geological Institute and State Institute of Environment Protection,
      Institute of Soil Science and Plant Cultivation, and with the regulations adopted
      in Germany, Denmark, the United States and Canada. Regarding the total heavy
      metal concentrations, water flowing into the examined reservoirs was not
      polluted. The highest concentrations of heavy metals were found in water flowing
      into the reservoirs in spring and summer. The heavy metal concentrations in
      sediments of the reservoirs at Krempna and Zeslawice were much higher than the
      concentrations of the elements discussed present in waters flowing into these
      reservoirs. 

PMID- 24679091
TI  - Trace level enrichment of lead from environmental water samples utilizing
      dispersive liquid-liquid microextraction and quantitative determination by
      graphite furnace atomic absorption spectrometry.
AB  - Dispersive liquid-liquid microextraction (DLLME) was developed and successfully
      applied, as a sample preconcentration and extraction method, for the
      determination of trace quantities of lead (Pb) in environmental water samples
      utilizing graphite furnace atomic absorption spectrometer (GFAAS). Experimental
      parameters optimized include; extraction and disperser solvent types and their
      volumes, pH, extraction period, effect of the co-existing ions and the amount of
      chelating agent, ammonium pyrrolidine dithiocarbamate (APDC). Under the optimized
      conditions, enrichment factor of 195 at 5 MUg L(-1) level and detection limit of
      0.16 MUg L(-1) were obtained. Linearity from 25-75 MUg L(-1) with R(2) of 0.995
      was achieved. The procedure was validated utilizing four environmental water
      samples at the spiking levels of 10 and 20 MUg L(-1) and the corresponding
      recoveries ranged from 89.6 to 95.1% and 91.6 to 97.1%, respectively, indicating
      the reliability and applicability of the method for selective extraction of trace
      level lead.

PMID- 24679092
TI  - Feasibility of electrochemical degradation of pharmaceutical pollutants in
      different aqueous matrices: optimization through design of experiments.
AB  - Electrochemical degradation of different effluents polluted with carbamazepine, a
      well-known refractory pharmaceutical contaminant, was addressed in this article.
      Ultrapure water (Milli-Q(TM) technology), surface water from a lake and urban
      wastewater were the matrices used to evaluate the feasibility of performing the
      electro-oxidation of carbamazepine. Specific designs of experiments were planned
      for each of the aqueous media. The initial carbamazepine concentration and the
      electric current density were considered as the operational variables. Although
      the optimal values of both variables follow the same trend in the three cases,
      significant differences are observed regarding the comparative influence of each
      variable on the degradation of carbamazepine. 

PMID- 24679093
TI  - Comparison of nitrogen removal rates and nitrous oxide production from enriched
      anaerobic ammonium oxidizing bacteria in suspended and attached growth reactors.
AB  - Attached growth-systems for the anaerobic ammonium oxidation (anammox) process
      have been postulated for implementation in the field. However, information about
      the anammox process in attached growth-systems is limited. This study compared
      nitrogen removal rates and nitrous oxide (N2O) production of enriched anammox
      cultures in both suspended and attached growth sequencing batch reactors (SBRs).
      Suspended growth reactors (SBR-S) and attached growth reactors using polystyrene
      sponge as a medium (SBR-A) were used in these experiments. After inoculation with
      an enriched anammox culture, significant nitrogen removals of ammonium (NH4 (+))
      and nitrite (NO2 (-)) were observed under NH4 (+):NO2 (-) ratios ranging from 1:1
      to 1:2 in both types of SBRs. The specific rates of total nitrogen removal in SBR
      S and SBR-A were 0.52 mg N/mg VSS-d and 0.44 mg N/mg VSS-d, respectively, at an
      NH4 (+):NO2 (-) ratio of 1:2. N2O production by the enriched anammox culture in
      both SBR-S and SBR-A was significantly higher at NH4 (+):NO2 (-) ratio of 1:2
      than at NH4 (+):NO2 (-) ratios of 1:1 and 1:1.32. In addition, N2O production was
      higher at a pH of 6.8 than at pH 7.3, 7.8, and 8.3 in both SBR-S and SBR-A. The
      results of this investigation demonstrate that the anammox process may avoid N2O
      emission by maintaining an NH4 (+):NO2 (-) ratio of less than 1:2 and pH higher
      than 6.8.

PMID- 24679095
TI  - Physiological aspects of the interaction of multi-walled carbon nanotubes with
      Beauveria bassiana (Balsamo) Vuillem in entomopathogenic spores.
AB  - The objective of the study was to evaluate the in vitro effect of aqueous
      suspensions of commercial multi-walled carbon nanotubes (MWCNTs) on spores of
      three entomopathogenic fungus species of Beauveria bassiana. Spores were placed
      in contact with MWCNTs for 1, 24, 72 and 216 h and then an in vitro evaluation in
      the subculture was performed on the linear growth of the vegetative mycelium of
      the spores after the contact with nanomaterial, as well as its sporulation after
      completion of the culture. No fungistatic effect of MWCNTs against B. bassiana
      spores was identified. Modification of vegetative mycelium surface growth in the
      culture of spores after contact with MWCNTs was mainly due to less effective
      inoculation, especially when shorter contact times with nanomaterial were
      applied. For one of the investigated strains, growth stimulation was observed in
      the culture of spores in contact with nanotubes for 72 and 216 h. Based on the
      significant intensification of sporulation observed in combination with the
      longest (216 h) contact with the investigated spore strains before culture with
      MWCNTs, it can be concluded that the tested nanomaterial constitutes a stress
      factor and may modify the metabolism of B. bassiana cells. Detailed evaluation of
      B. bassiana metabolic changes induced by MWCNTs should be conducted.

PMID- 24679094
TI  - Effect of dissolved oxygen and temperature on macromolecular composition and PHB
      storage of activated sludge.
AB  - The macromolecular composition of activated sludge (lipids, intracellular
      proteins and intracellular polysaccharides) was studied together with its
      capacity to store macromolecules such as polyhydroxybutyrate (PHB) in a
      conventional activated sludge system fed with synthetic sewage water at an
      organic load rate of 1.0 kg COD/(m(3).d), varying the dissolved oxygen (DO) and
      temperature. Six DO concentrations (0.8, 1.0, 1.5, 2.0, 2.5 and 8 mg/L) were
      studied at 20 degrees C with a sludge retention time (SRT) of 6 days. In
      addition, four temperatures (10oC, 15oC, 20oC and 30oC) were assessed at constant
      DO (2 mg/L) with 2 days SRT in a second experimental run. The highest lipid
      content in the activated sludge was 95.6 mg/g VSS, obtained at 30 degrees C, 2
      mg/L of DO and a SRT of 2 days. The highest content of intracellular proteins in
      the activated sludge was 87.8 mg/g VSS, obtained at 20 degrees C, 8 mg/L of DO
      and a SRT of 6 days. The highest content of intracellular polysaccharides in the
      activated sludge was 76.6 mg/g VSS, which was achieved at 20 degrees C, a SRT of
      6 days and a wide range of DO. The activated sludge PHB storage was very low for
      all the conditions studied.

PMID- 24679096
TI  - Three new alkaloids from the fruits of Morus alba.
AB  - From the fruits of Morus alba, three new alkaloids, mulbaines A (1), B (2), and C
      (3) were isolated. The structures of these compounds were elucidated on the basis
      of spectroscopic methods (UV, IR, HR-ESI-MS, 1D, and 2D NMR). 

PMID- 24679098
TI  - Scalar relaxation of the second kind. A potential source of information on the
      dynamics of molecular movements. 3. A (13)C nuclear spin relaxation study of
      CBrX3 (X = Cl, CH3, Br) molecules.
AB  - Continuing studies based on measurements of the nuclear spin relaxation rates
      running via the SC2 mechanism (scalar relaxation of the second kind), we present
      in this work the results obtained for three bromo compounds: CBrCl3, (CH3)3CBr,
      and CBr4. A careful separation of saturation-recovery curves, measured for
      signals of (13)C nuclei at 7.05 and 11.7 T on two components, has provided the
      longitudinal SC2 relaxation rates of carbon signals in (79)Br and (81)Br
      containing isotopomers of the investigated compounds. These data have enabled
      experimental determination of spin-spin coupling constants and relaxation rates
      of quadrupole bromine nuclei, both types of parameters being hardly accessible by
      direct measurements. Investigation of the relaxation behavior of these molecules,
      being of similar size and shape, has provided quite different practical and
      interpretational problems which are likely to be encountered in relaxation
      studies of many other carbon-bromine systems. In order to evaluate the quality of
      the obtained experimental results, advanced theoretical calculations of the
      indirect (1)J((13)C,(79)Br) coupling constants, magnetic shielding of carbon
      nuclei, and quadrupole coupling constants of bromines in the investigated
      compounds have been performed and compared with the experimental values.
      Relatively small divergences between experiment and theory have been found. The
      contributions of the relativistic effects to the values of the discussed
      parameters have been tentatively estimated. 

PMID- 24679097
TI  - High levels of procoagulant factors mediate the association between free
      thyroxine and the risk of venous thrombosis: the MEGA study.
AB  - BACKGROUND: Thyroid hormone affects the coagulation system, but its effect on
      clinical disease is not clear. We determined the associations of levels of free
      thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase
      antibodies (antiTPO) with levels of coagulation factors and the risk of venous
      thrombosis. METHODS: In a large population based case-control study (Multiple
      Environmental and Genetic Assessment of risk factors for venous thrombosis study)
      on the etiology of venous thrombosis, we determined the levels of FT4, TSH,
      antiTPO, factor FII, FVII, FVIII, FIX, FX, von Willebrand factor (VWF),
      antithrombin, protein C, protein S and fibrinogen in 2177 cases and 2826
      controls. RESULTS: High levels of FT4 were associated with increased
      concentrations of procoagulant factors, and not with levels of anticoagulant
      factors. High levels of FT4 were also associated with the risk of venous
      thrombosis, up to an odds ratio (OR) of 2.2 (95% confidence interval [CI] 1.0
      4.6) for levels above 24.4 pm relative to FT4 levels between 15.5 and 18.9 pm. In
      11 cases and one control, clinical hyperthyroidism had been diagnosed within a
      year of the thrombotic event, leading to an OR of 17.0 (95% CI 2.2-133.0) for
      thrombosis. The ORs approached unity after adjustment for FVIII and VWF, which
      suggests that the effect was mediated by these factors. Low TSH levels were also,
      but less evidently, associated with thrombosis, whereas there was no association
      between antiTPO and venous thrombosis risk. CONCLUSIONS: High levels of FT4
      increase the concentrations of the procoagulant proteins FVIII, FIX, fibrinogen,
      and VWF, and by this mechanism increase the risk of venous thrombosis.

PMID- 24679099
TI  - Liver toxicity during temozolomide chemotherapy caused by Chinese herbs.
AB  - BACKGROUND: Complementary and alternative medicine is often used by patients with
      malignant glioma. Although several interactions of various alternative agents
      with chemotherapy are known, none has been described for temozolomide so far.
      CASE PRESENTATION: We report the case of severe liver toxicity with jaundice
      during radiochemotherapy with temozolomide likely due to interaction with a
      popular Chinese herbal formula after surgery for glioblastoma. After cessation of
      the herbal formula as well as the chemotherapy liver enzymes slowly normalized.
      Due to tumor progression the patient was retreated with temozolomide for 5 cycles
      without toxicity. Because of further progression combination treatment of
      bevacizumab and irinotecan was started and again no liver toxicity was observed.
      CONCLUSIONS: We conclude that the observed toxicity with jaundice was probably
      caused by an interaction of this popular Chinese formula and temozolomide. This
      is the first report about a relevant interaction of temozolomide and any herbal
      formula.

PMID- 24679100
TI  - Effect of vitamin D supplementation on muscle energy phospho-metabolites: a 31P
      magnetic resonance spectroscopy-based pilot study.
AB  - There are several published reports on the prevalence of low vitamin D levels in
      otherwise healthy Indian population. Vitamin D deficiency has shown variable
      effect on muscle performance and strength but there is paucity of data on the
      effect of vitamin D deficiency on muscle energy metabolism. The present study was
      proposed to investigate the influence of severe vitamin D deficiency on high
      energy metabolite levels in resting skeletal muscle and thereafter, monitor the
      response after vitamin D supplementation using 31P magnetic resonance
      spectroscopy (MRS). Study was conducted on 19 otherwise healthy subjects but with
      low serum 25(OH)D levels (<5 ng/ml). Subjects were supplemented with
      cholecalciferol at a dose of 60,000 IU/week for 12 weeks. MRS measurements of
      inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiester (PDE) and ATP of
      the calf muscle were taken pre- and post-vitamin D supplementation. The study
      revealed significantly increased PCr/Pi ratio and decreased [Pi] and PDE/ATP
      ratio with raised serum 25(OH)D levels after 12 weeks of supplementation. The
      study indicates that serum 25(OH)D level plays an important role in improving the
      skeletal muscle energy metabolism and vitamin D deficiency might be one of the
      primary reasons for prevalence of low PCr/Pi ratio and high PDE values in normal
      Indian population as reported earlier. The findings of this preliminary study are
      highly encouraging and warrant further in-depth research, involving larger number
      of subjects of different age groups, regions and socio-economic sections of the
      society to further strengthen a correlation between vitamin D levels and muscle
      energy metabolism.

PMID- 24679102
TI  - Biofilm prevention on cochlear implants.
AB  - OBJECTIVES: To examine the efficiency of a bacteria-resistant coating for the
      polydimethylsiloxane (PDMS) casing of cochlear implants. METHODS: The coatings
      are based on thin titania films that are made by liquid phase deposition or
      atomic layer deposition. The antibacterial activity of the coating was tested by
      two different detection assays: BCA protein and confocal microscopy. RESULTS:
      Coating the PDMS with thin films (10-40 nm) of titania significantly reduces the
      accumulation of bacteria. DISCUSSION: Thin oxide films made under conditions that
      do not undermine the integrity of polymeric materials can be used as anti
      microbial coatings for soft polymers such as the PDMS that is used as a casing
      for cochlear implants or other medical devices.

PMID- 24679101
TI  - Liver Transplant for Children With Hepatocellular Carcinoma and Hereditary
      Tyrosinemia Type 1.
AB  - OBJECTIVES: This study sought to determine the prevalence of hepatocellular
      carcinoma and other premalignant lesions in children with hereditary tyrosinemia
      type 1 who had undergone an orthotopic liver transplant at the Shiraz Transplant
      Center, in Shiraz, Iran. MATERIALS AND METHODS: Between September 2006, and June
      2011, thirty-six patients with hereditary tyrosinemia type 1 received a liver
      transplant from a deceased (whole or split) or a living-related donor. Clinical
      records and pathologic specimens, before and after surgery, for each case were
      reviewed. In addition, ultrasound, abdominal computed tomographic imaging scan
      findings, and levels of alpha-fetoprotein were recorded. RESULTS: Twenty-two
      patients with hepatic nodules larger than 10 mm underwent a Tru-Cut needle biopsy
      before their liver transplant. In 2 patients, a diagnosis of hepatocellular
      carcinoma was made by pathologic examination; in the other 20, cirrhosis was
      confirmed with no evidence of malignancy. After pathologic examination of the
      explanted livers, the largest nodules in the 36 patients were 35 mm. Five cases
      had at least 1 nodule of hepatocellular carcinoma. Three of the other patients
      had small cell dysplasia in some of nodules. All 5 cases with hepatocellular
      carcinoma were patients older than 2 years of age (19 patients were older than 2
      years of age). All patients with hepatocellular carcinoma received pretransplant
      nitisinone treatment. All patients with hepatocellular carcinoma after their
      liver transplant are alive at the time of this writing. CONCLUSIONS: The
      prevalence of cell dysplasia and hepatocellular carcinoma in children with
      hereditary tyrosinemia type 1 in our study is not as high as that reported
      previously, so it appears that patients older than 2 years of age require a liver
      transplant.

PMID- 24679103
TI  - The penumbra of learning: a statistical theory of synaptic tagging and capture.
AB  - Learning in humans and animals is accompanied by a penumbra: Learning one task
      benefits from learning an unrelated task shortly before or after. At the cellular
      level, the penumbra of learning appears when weak potentiation of one synapse is
      amplified by strong potentiation of another synapse on the same neuron during a
      critical time window. Weak potentiation sets a molecular tag that enables the
      synapse to capture plasticity-related proteins synthesized in response to strong
      potentiation at another synapse. This paper describes a computational model which
      formalizes synaptic tagging and capture in terms of statistical learning
      mechanisms. According to this model, synaptic strength encodes a probabilistic
      inference about the dynamically changing association between pre- and post
      synaptic firing rates. The rate of change is itself inferred, coupling together
      different synapses on the same neuron. When the inputs to one synapse change
      rapidly, the inferred rate of change increases, amplifying learning at other
      synapses.

PMID- 24679104
TI  - Older people's perceived causes of and strategies for dealing with social
      isolation.
AB  - OBJECTIVE: To explicate lay theories relating to social isolation and to identify
      instances of positive deviance to inform future efforts to encourage older people
      to participate in protective behaviors. METHOD: Twelve focus groups and 20
      individual interviews were conducted with Australians aged 40 years and older.
      Data were collected in metropolitan and regional areas. The age threshold was
      based on the need to generate formative research to inform interventions to
      encourage people to engage in preventive behaviors prior to reaching older age
      when they become more susceptible to social isolation. RESULTS: Two primary lay
      theories were identified in the data. These are related to the recognized
      importance of social connection and the belief that forming new social
      connections becomes more difficult with age due to a range of individual and
      external factors. Examples of positive deviance that were identified included
      viewing overcoming social isolation as an incremental process, being prepared to
      be the instigator of social interaction, and adopting an external focus.
      CONCLUSION: The findings suggest that the provision of a broad range of group
      activities may need to be combined with a focused approach to targeting and
      approaching those most at risk to reduce the burden of social isolation at a
      population level.

PMID- 24679106
TI  - How does Nishibayashi's molybdenum complex catalyze dinitrogen reduction to
      ammonia?
AB  - Recently, Nishibayashi et al. reported a dimolybdenum-dinitrogen complex that is
      catalytic for complete reduction of dinitrogen to ammonia. This catalyst is
      different from the Schrock molybdenum catalyst in two fundamental aspects: it
      contains two metal centers, and the oxidation state is Mo(0) instead of Mo(III).
      We show that a remarkable feature of the bimetallic complex is the bond-mediated
      delocalized electronic states, resulting from the two metal centers bridged by a
      dinitrogen ligand. Using first-principles calculations, we found that this
      property makes the bimetallic complex the effective catalyst, as opposed to the
      originally postulated monometallic fragment. A favorable reaction pathway is
      identified, and the nature of the intermediates is examined. Furthermore, studies
      of the intermediate states led us to propose possible deactivation processes of
      the catalyst. The finding that the central bimetallic unit (Mo-N2-Mo) is relevant
      for catalytic activity may provide a guideline for the development of more
      efficient dinitrogen-reducing catalysts. 

PMID- 24679105
TI  - Distinct polymicrobial populations in a chronic foot ulcer with implications for
      diagnostics and anti-infective therapy.
AB  - BACKGROUND: Polymicrobial infections caused by combinations of different bacteria
      are being detected with an increasing frequency. The evidence of such complex
      infections is being revealed through the use of novel molecular and culture
      independent methods. Considerable progress has been made in the last decade
      regarding the diagnostic application of such molecular techniques. In particular,
      16S rDNA-based sequencing and even metagenomic analyses have been successfully
      used to study the microbial diversity in ecosystems and human microbiota. Here,
      we utilized denaturing high-performance liquid chromatography (DHPLC) as a
      diagnostic tool for identifying different bacterial species in complex clinical
      samples of a patient with a chronic foot ulcer. CASE PRESENTATION: A 45-year-old
      female suffered from a chronic 5x5cm large plantar ulcer located in the posterior
      calcaneal area with subcutaneous tissue infection and osteomyelitis. The chronic
      ulcer developed over a period of 8 years. Culture and DHPLC revealed a distinct
      and location-dependent polymicrobial infection of the ulcer. The analysis of a
      superficial biopsy revealed a mixture of Staphylococcus aureus, Proteus vulgaris,
      and Fusobacterium nucleatum, whereas the tissue-deep biopsy harbored a mixture of
      four different bacterial species, namely Gemella morbillorum, Porphyromonas
      asaccharolytica, Bacteroides fragilis, and Arcanobacterium haemolyticum.
      CONCLUSIONS: This clinical case highlights the difficulties in assessing
      polymicrobial infections where a mixture of fastidious, rapid and slow growing
      bacteria as well as anaerobes exists as structured communities within the tissue
      architecture of chronic wound infections. The diagnosis of this multilayered
      polymicrobial infection led to a microbe-adapted antibiotic therapy, targeting
      the polymicrobial nature of this infection in addition to a standard local wound
      treatment. However, a complete wound closure could not be achieved due to the
      long-lasting extensive destruction of tissue.

PMID- 24679107
TI  - Antimicrobial susceptibility patterns of Ureaplasma species and Mycoplasma
      hominis in pregnant women.
AB  - BACKGROUND: Genital mycoplasmas colonise up to 80% of sexually mature women and
      may invade the amniotic cavity during pregnancy and cause complications.
      Tetracyclines and fluoroquinolones are contraindicated in pregnancy and
      erythromycin is often used to treat patients. However, increasing resistance to
      common antimicrobial agents is widely reported. The purpose of this study was to
      investigate antimicrobial susceptibility patterns of genital mycoplasmas in
      pregnant women. METHODS: Self-collected vaginal swabs were obtained from 96
      pregnant women attending an antenatal clinic in Gauteng, South Africa. Specimens
      were screened with the Mycofast Revolution assay for the presence of Ureaplasma
      species and Mycoplasma hominis. The antimicrobial susceptibility to levofloxacin,
      moxifloxacin, erythromycin, clindamycin and tetracycline were determined at
      various breakpoints. A multiplex polymerase chain reaction assay was used to
      speciate Ureaplasma positive specimens as either U. parvum or U. urealyticum.
      RESULTS: Seventy-six percent (73/96) of specimens contained Ureaplasma spp.,
      while 39.7% (29/73) of Ureaplasma positive specimens were also positive for M.
      hominis. Susceptibilities of Ureaplasma spp. to levofloxacin and moxifloxacin
      were 59% (26/44) and 98% (43/44) respectively. Mixed isolates (Ureaplasma species
      and M. hominis) were highly resistant to erythromycin and tetracycline (both 97%
      resistance). Resistance of Ureaplasma spp. to erythromycin was 80% (35/44) and
      tetracycline resistance was detected in 73% (32/44) of Ureaplasma spp. Speciation
      indicated that U. parvum was the predominant Ureaplasma spp. conferring
      antimicrobial resistance. CONCLUSIONS: Treatment options for genital mycoplasma
      infections are becoming limited. More elaborative studies are needed to elucidate
      the diverse antimicrobial susceptibility patterns found in this study when
      compared to similar studies. To prevent complications in pregnant women, the
      foetus and the neonate, routine screening for the presence of genital mycoplasmas
      is recommended. In addition, it is recommended that antimicrobial susceptibility
      patterns are determined.

PMID- 24679108
TI  - Integration of substance use disorder services with primary care: health center
      surveys and qualitative interviews.
AB  - BACKGROUND: Each year, nearly 20 million Americans with alcohol or illicit drug
      dependence do not receive treatment. The Affordable Care Act and parity laws are
      expected to result in increased access to treatment through integration of
      substance use disorder (SUD) services with primary care. However, relatively
      little research exists on the integration of SUD services into primary care
      settings. Our goal was to assess SUD service integration in California primary
      care settings and to identify the practice and policy facilitators and barriers
      encountered by providers who have attempted to integrate these services. METHODS:
      Primary survey and qualitative interview data were collected from the population
      of federally qualified health centers (FQHCs) in five California counties known
      to be engaged in SUD integration efforts was surveyed. From among the
      organizations that responded to the survey (78% response rate), four were
      purposively sampled based on their level of integration. Interviews were
      conducted with management, staff, and patients (n=18) from these organizations to
      collect further qualitative information on the barriers and facilitators of
      integration. RESULTS: Compared to mental health services, there was a trend for
      SUD services to be less integrated with primary care, and SUD services were rated
      significantly less effective. The perceived difference in effectiveness appeared
      to be due to provider training. Policy suggestions included expanding the SUD
      workforce that can bill Medicaid, allowing same-day billing of two services,
      facilitating easier reimbursement for medications, developing the workforce, and
      increasing community SUD specialty care capacity. CONCLUSIONS: Efforts to
      integrate SUD services with primary care face significant barriers, many of which
      arise at the policy level and are addressable.

PMID- 24679110
TI  - Inflammation is associated with a worsening of presbycusis: evidence from the MRC
      national study of hearing.
AB  - OBJECTIVE: Inflammaging, a state of chronic inflammation in the elderly, is now
      thought to be a key element of the ageing process and contributor to age-related
      disease. In a previously published study, we identified a significant association
      between inflammation levels and severity of presbycusis among individuals aged 63
      to 73 ('younger old") within an available audiometric range 0.5 to 4 kHz. Our aim
      was to see if this association would be identified among participants in the MRC
      national study of hearing, and whether the strength of the association would
      increase with greater age, or for very low or very high audiometric frequencies.
      DESIGN: Cross-sectional analysis of cohort data. STUDY SAMPLE: Three hundred and
      sixty community-dwelling adults age 60 years and over, representing all those
      with white blood cell count and audiometric data available. RESULTS: A
      significant independent association between (higher) WBC and (worse) hearing
      level was identified. This effect increased with age. The strongest association
      was among those over 75, for whom average hearing threshold levels among those
      with lower WBC was 17 dB better than those with higher WBC. CONCLUSIONS: The
      current findings support an association between inflammaging (a condition
      potentially amenable to pharmacological treatment or lifestyle management) and
      presbycusis.

PMID- 24679109
TI  - Observation of the extent of smoking in a mental health inpatient facility with a
      smoke-free policy.
AB  - BACKGROUND: People with a mental illness experience a higher burden of smoking
      related disease. Smoke-free policies in mental health facilities provide an
      opportunity to reduce smoking-related harms for patients and staff alike. Limited
      evidence regarding the effect of such policies on preventing smoking in mental
      health facilities has been reported. The aims of this study are to describe the
      extent of smoking and the provision of nicotine replacement therapy (NRT) to
      patients in a mental health facility with a smoke-free policy. METHODS: Cross
      sectional studies of smoking (cigarette butt count and observed smoking) and
      nicotine dependence treatment (patient record audit) were undertaken over 9
      consecutive weekdays in one mental health facility in Australia. A smoke-free
      policy incorporating a total smoking ban and guidelines for treating nicotine
      dependence among patients was implemented in the facility 4 years prior to the
      study. RESULTS: Two thousand one hundred and thirty seven cigarette butts were
      collected and 152 occasions of people smoking were observed. Staff members were
      observed to enforce the policy on 66% of occasions. Use of NRT was recorded for
      53% of patients who were smokers. CONCLUSION: Implementation of the smoke-free
      policy was less than optimal and as a consequence ineffective in eliminating
      smoking and in optimising the provision of NRT. Additional strategies to improve
      the provision of nicotine dependence treatment to patients and the monitoring of
      adherence are needed to ensure the intended benefits of smoke-free policies are
      realised.

PMID- 24679111
TI  - Mechanism of the formation of a Mn-based CO2 reduction catalyst revealed by pulse
      radiolysis with time-resolved infrared detection.
AB  - Using a new technique, which combines pulse radiolysis with nanosecond time
      resolved infrared (TRIR) spectroscopy in the condensed phase, we have conducted a
      detailed kinetic and mechanistic investigation of the formation of a Mn-based CO2
      reduction electrocatalyst, [Mn((t)Bu2-bpy)(CO)3]2 ((t)Bu2-bpy = 4,4'-(t)Bu2-2,2'
      bipyridine), in acetonitrile. The use of TRIR allowed, for the first time, direct
      observation of all the intermediates involved in this process. Addition of excess
      [(n)Bu4N][HCO2] to an acetonitrile solution of fac-MnBr((t)Bu2-bpy)(CO)3 results
      in its quantitative conversion to the Mn-formate complex, fac-Mn(OCHO)((t)Bu2
      bpy)(CO)3, which is a precatalyst for the electrocatalytic reduction of CO2.
      Formation of the catalyst is initiated by one-electron reduction of the Mn
      formate precatalyst, which produces the bpy ligand-based radical. This radical
      undergoes extremely rapid (tau = 77 ns) formate dissociation accompanied by a
      free valence shift to yield the five-coordinate Mn-based radical, Mn(*)((t)Bu2
      bpy)(CO)3. TRIR data also provide evidence that the Mn-centered radical does not
      bind acetonitrile prior to its dimerization. This reaction occurs with a
      characteristically high radical-radical recombination rate (2kdim = (1.3 +/- 0.1)
      * 10(9) M(-1) s(-1)), generating the catalytically active Mn-Mn bound dimer. 

PMID- 24679112
TI  - Monitoring the BK virus in liver transplant recipients: a prospective
      observational study.
AB  - OBJECTIVES: Because of the controversy regarding the effects of BK virus on
      nonrenal solid-organ transplant, we detected the BK virus via different methods
      and its effect on clinical findings, liver and kidney functions, and graft
      dysfunction in liver transplant recipients. MATERIALS AND METHODS: This
      prospective cohort study comprised patients over the age of 18, who consecutively
      received liver transplant from January 1 to December 31, 2011. The patients were
      examined once, every 2 weeks, for the first 3 months after transplant. Clinical
      findings were evaluated on each examination; blood and urine samples were
      collected, BK virus DNA was assessed with real-time polymerase chain reaction,
      and the presence of decoy cells (which are epithelial cells with large nuclei and
      large basophilic inclusions) in the urine was investigated. Patients were
      followed-up for 1 year to see if rejection occurred. RESULTS: Five of 39 patients
      (12.8%) showed BK viremia; 11 patients (28.2%) showed BK viruria, and 13 (33.3%)
      showed decoy cells. No statistically significant differences were found between
      BK virus positive and negative groups, respecting demographic variables, kidney
      and liver functions, and graft survival. BK virus DNA positivity in blood was the
      standard, while decoy cell assessment in urine and BK virus polymerase chain
      reaction test sensitivity in urine was 40%. CONCLUSIONS: No matter the method
      used to detect BK virus in the urine, the negativity of the tests is more
      valuable than their positivity. Although no statistically significant difference
      was found between the groups, we concluded that BK virus is a factor that should
      be considered when unexplained deterioration in kidney and liver function tests
      is observed in liver transplant recipients. Prospective studies with larger
      numbers of patients are warranted.

PMID- 24679113
TI  - Novel in vitro systems for prediction of veterinary drug residues in ovine milk
      and dairy products.
AB  - A new in vitro tool was developed for the identification of veterinary substrates
      of the main drug transporter in the mammary gland. These drugs have a much higher
      chance of being concentrated into ovine milk and thus should be detectable in
      dairy products. Complementarily, a cell model for the identification of compounds
      that can inhibit the secretion of drugs into ovine milk, and thus reduce milk
      residues, was also generated. The ATP-binding cassette transporter G2 (ABCG2) is
      responsible for the concentration of its substrates into milk. The need to
      predict potential drug residues in ruminant milk has prompted the development of
      in vitro cell models over-expressing ABCG2 for these species to detect veterinary
      drugs that interact with this transporter. Using these models, several substrates
      for bovine and caprine ABCG2 have been found, and differences in activity between
      species have been reported. However, despite being of great toxicological
      relevance, no suitable in vitro model to predict substrates of ovine ABCG2 was
      available. New MDCKII and MEF3.8 cell models over-expressing ovine ABCG2 were
      generated for the identification of substrates and inhibitors of ovine ABCG2.
      Five widely used veterinary antibiotics (marbofloxacin, orbifloxacin,
      sarafloxacin, danofloxacin and difloxacin) were discovered as new substrates of
      ovine ABCG2. These results were confirmed for the bovine transporter and its
      Y581S variant using previously generated cell models. In addition, the avermectin
      doramectin was described as a new inhibitor of ruminant ABCG2. This new rapid
      assay to identify veterinary drugs that can be concentrated into ovine milk will
      potentially improve detection and monitoring of veterinary drug residues in ovine
      milk and dairy products. 

PMID- 24679114
TI  - Increased hospital volume is associated with improved outcomes following
      abdominal-based breast reconstruction.
AB  - Previous studies of outcomes following abdominal-based breast reconstruction
      largely use data from single-centre/surgeon experience. Such studies are limited
      in evaluating the effect of operative volume on outcomes. Abdominal-based breast
      reconstructive procedures were identified in the 2009-2010 HCUP Nationwide
      Inpatient Sample. Outcomes included in-hospital microvascular complications in
      free flap cases (requiring exploration/anastomosis revision), procedure-related
      and total complications in all cases, and length of stay (LOS). High-volume
      hospitals were defined as 90th percentile of case volume or higher (>30
      flaps/year). Univariate and multivariate analyses were performed to identify
      predictors of outcomes. Of the 4107 patients identified, mean age was 50.7 years;
      71% were white, 68% underwent free flap reconstruction, and 25% underwent
      bilateral reconstruction. The total complication rate was 13.2%, and the
      microvascular complication rate was 7.0%. Mean LOS was 4.5 days. There were 436
      hospitals; 59% of cases were performed at high-volume institutions. Patients at
      high-volume hospitals more often underwent free flap reconstruction compared to
      low-volume hospitals (82.4% vs 50.5%, p < 0.001). On unadjusted analysis,
      microvascular complication rates of 6.4% vs 8.2% were observed for high-volume
      compared to low-volume hospitals (p = 0.080). After adjusting for case-mix, high
      volume hospitals were associated with a decreased likelihood of suffering a
      microvascular complication (OR = 0.71, p = 0.026), procedure-related complication
      (OR = 0.79, p = 0.033), or total complication (OR = 0.75, p = 0.004). The
      majority of cases nationwide are performed at a small number of high-volume
      hospitals. These hospitals appear to discharge patients earlier and have lower
      microvascular, procedure-related, and total complication rates when controlling
      for case-mix.

PMID- 24679115
TI  - Primary ulnar superficial slip resection in complicated trigger finger.
AB  - Long standing trigger finger, often present for 6 months to years before
      consulting, can result in a lack of extension, which is often painful and may
      persist after section of the A1 pulley. The ulnar superficial slip resection
      (USSR) was introduced by Le Viet to address this problem. It is hypothesised that
      primary section of the A1 pulley with USSR resolves both extension lack and pain
      in longstanding trigger fingers with a painful extension lack. This retrospective
      study reviewed the results of primary USSR for longstanding trigger fingers (6
      months or more) with painful extension lack in 18 patients. Locking was resolved
      and full extension was acquired in all cases (100%). Satisfaction rate was high
      (89%) and disability returned to normal after surgery. In two patients,
      satisfaction was low due to residual loss of flexion as a result of
      osteoarthritis and cold intolerance in another. It is concluded that the USSR
      procedure is a valuable primary surgical option in complicated trigger finger
      with painful extension lack caused by flexor tendon tendinosis.

PMID- 24679116
TI  - Attritional rupture of the extensor pollicis longus tendon by an osseous spur
      more than 30 years after wrist injury: a case report.
AB  - A 46-year-old woman sustained a rupture of the extensor pollicis longus tendon
      more than 30 years after wrist injury. She was successfully treated with palmaris
      longus tendon graft and excision of the osseous spur. Attrition of the extensor
      pollicis longus tendon by a newly formed osseous spur was the major mechanism.

PMID- 24679118
TI  - Comment on Electrolytic manipulation of persulfate reactivity by iron electrodes
      for TCE degradation in groundwater.

PMID- 24679119
TI  - Relationship between child survival and malaria transmission: an analysis of the
      malaria transmission intensity and mortality burden across Africa (MTIMBA)
      project data in Rufiji demographic surveillance system, Tanzania.
AB  - BACKGROUND: The precise nature of the relationship between malaria mortality and
      levels of transmission is unclear. Due to methodological limitations, earlier
      efforts to assess the linkage have lead to inconclusive results. The malaria
      transmission intensity and mortality burden across Africa (MTIMBA) project
      initiated by the INDEPTH Network collected longitudinally entomological data
      within a number of sites in sub-Saharan Africa to study this relationship. This
      work linked the MTIMBA entomology database with the routinely collected vital
      events within the Rufiji Demographic Surveillance System to analyse the
      transmission-mortality relation in the region. METHODS: Bayesian Bernoulli spatio
      temporal Cox proportional hazards models with village clustering, adjusted for
      age and insecticide-treated nets (ITNs), were fitted to assess the relation
      between mortality and malaria transmission measured by entomology inoculation
      rate (EIR). EIR was predicted at household locations using transmission models
      and it was incorporated in the model as a covariate with measure of uncertainty.
      Effects of covariates estimated by the model are reported as hazard ratios (HR)
      with 95% Bayesian confidence interval (BCI) and spatial and temporal parameters
      are presented. RESULTS: Separate analysis was carried out for neonates, infants
      and children 1-4 years of age. No significant relation between all-cause
      mortality and intensity of malaria transmission was indicated at any age in
      childhood. However, a strong age effect was shown. Comparing effects of ITN and
      EIR on mortality at different age categories, a decrease in protective efficacy
      of ITN was observed (i.e. neonates: HR = 0.65; 95% BCI:0.39-1.05; infants: HR =
      0.72; 95% BCI:0.48-1.07; children 1-4 years: HR = 0.88; 95% BCI:0.62-1.23) and
      reduction on the effect of malaria transmission exposure was detected (i.e.
      neonates: HR = 1.15; 95% BCI:0.95-1.36; infants: HR = 1.13; 95% BCI:0.98-1.25;
      children 1-4 years: HR = 1.04; 95% BCI:0.89-1.18). A very strong spatial
      correlation was also observed. CONCLUSION: These results imply that assessing the
      malaria transmission-mortality relation involves more than the knowledge on the
      performance of interventions and control measures. This relation depends on the
      levels of malaria endemicity and transmission intensity, which varies
      significantly between different settings. Thus, sub-regions analyses are
      necessary to validate and assess reproducibility of findings.

PMID- 24679120
TI  - Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.
AB  - Hippocampal functions are influenced by steroid hormones, such as testosterone
      and estradiol. It has been demonstrated that hippocampus-derived steroid hormones
      play important roles in neuronal protection and synapse formation. Our research
      groups have demonstrated that estradiol is de novo synthesized in the rat
      hippocampus. However, the mechanism(s) regulating this synthesis remains unclear.
      It has been reported that tributyltin, an environmental pollutant, binds to the
      retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like
      tumor cells. This compound can penetrate the blood brain barrier, and tends to
      accumulate in the brain. Based on these facts, we hypothesized that tributyltin
      could influence the hippocampal estradiol synthesis. A concentration of 0.1 MUM
      tributyltin induced an increase in the mRNA content of P450(17alpha) and P450arom
      in hippocampal slices, as determined using real-time PCR. The transcript levels
      of other steroidogenic enzymes and a steroidogenic acute regulatory protein were
      not affected. The estradiol level in rat hippocampal slices was subsequently
      determined using a radioimmunoassay. We found that the estradiol synthesis was
      stimulated by ~2-fold following a 48-h treatment with 0.1 MUM tributyltin, and
      this was accompanied by transcriptional activation of P450(17alpha) and P450arom.
      Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the
      transcription of specific steroidogenic enzymes.

PMID- 24679121
TI  - The relationship between verbal and nonverbal auditory signal processing in
      conduction aphasia: behavioral and anatomical evidence for common decoding
      mechanisms.
AB  - The processing of nonverbal auditory stimuli has not yet been sufficiently
      investigated in patients with aphasia. On the basis of a duration discrimination
      task, we examined whether patients with left-sided cerebrovascular lesions were
      able to perceive time differences in the scale of approximately 150 ms. Further
      linguistic and memory-related tasks were used to characterize more exactly the
      relationships in the performances between auditory nonverbal task and selective
      linguistic or mnemonic disturbances. All examined conduction aphasics showed
      increased thresholds in the duration discrimination task. The low thresholds on
      this task were in a strong correlative relation to the reduced performances in
      repetition and working memory task. This was interpreted as an indication of a
      pronounced disturbance in integrating auditory verbal information into a long
      term window (sampling disturbance) resulting in an additional load of working
      memory. In order to determine the lesion topography of patients with sampling
      disturbances, the anatomical and psychophysical data were correlated on the basis
      of a voxelwise statistical approach. It was found that tissue damage extending
      through the insula, the posterior superior temporal gyrus, and the supramarginal
      gyrus causes impairments in sequencing of time-sensitive information. 

PMID- 24679122
TI  - Serotonin transporter and BDNF polymorphisms interact to predict trait worry.
AB  - BACKGROUND AND OBJECTIVES: Excessive worry is associated with a range of
      psychological disorders. While previous studies have examined genes associated
      with a range of different anxiety phenotypes, none have explored genes
      specifically associated with the general tendency to worry. DESIGN: The present
      study tested associations between trait worry and functional polymorphisms of
      three candidate genes: the serotonin transporter-linked polymorphic region (5
      HTTLPR) of the SLC6A4 gene, the Val66Met region of the brain-derived neurotrophic
      factor (BDNF) gene, and the Val158Met region of the catechol-O-methyltransferase
      (COMT) gene. METHODS: A heterogeneous sample of adult participants (n=173)
      completed the Penn State Worry Questionnaire (PSWQ) and provided DNA samples for
      genotyping. RESULTS: Results revealed a significant interaction between 5-HTTLPR
      and BDNF genotypes predicting levels of worry. Specifically, there was a
      significant positive association between 5-HTTLPR short alleles and PSWQ scores,
      but only in BDNF met allele carriers. COMT genotype was not significantly
      associated levels of worry, nor did COMT interact with 5-HTTLPR or BDNF genotypes
      to predict PSWQ scores. CONCLUSIONS: These findings provide preliminary evidence
      about the putative genetic etiology of worrying. Key limitations of the present
      study and corresponding directions for future research on this topic are
      discussed.

PMID- 24679123
TI  - Cellular reprogramming for pancreatic beta-cell regeneration: clinical potential
      of small molecule control.
AB  - Recent scientific breakthroughs in stem cell biology suggest that a sustainable
      treatment approach to cure diabetes mellitus (DM) can be achieved in the near
      future. However, the transplantation complexities and the difficulty in obtaining
      the stem cells from adult cells of pancreas, liver, bone morrow and other cells
      is a major concern. The epoch-making strategy of transcription-factor based
      cellular reprogramming suggest that these barriers could be overcome, and it is
      possible to reprogram any cells into functional beta cells. Contemporary
      biological and analytical techniques help us to predict the key transcription
      factors needed for beta-cell regeneration. These beta cell-specific transcription
      factors could be modulated with diverse reprogramming protocols. Among cellular
      reprogramming strategies, small molecule approach gets proclaimed to have better
      clinical prospects because it does not involve genetic manipulation. Several
      small molecules targeting certain epigenetic enzymes and/or signaling pathways
      have been successful in helping to induce pancreatic beta-cell specification.
      Recently, a synthetic DNA-based small molecule triggered targeted transcriptional
      activation of pancreas-related genes to suggest the possibility of achieving
      desired cellular phenotype in a precise mode. Here, we give a brief overview of
      treating DM by regenerating pancreatic beta-cells from various cell sources.
      Through a comprehensive overview of the available transcription factors, small
      molecules and reprogramming strategies available for pancreatic beta-cell
      regeneration, this review compiles the current progress made towards the
      generation of clinically relevant insulin-producing beta-cells. 

PMID- 24679125
TI  - One-dimensional helical transport in topological insulator nanowire
      interferometers.
AB  - The discovery of three-dimensional (3D) topological insulators opens a gateway to
      generate unusual phases and particles made of the helical surface electrons,
      proposing new applications using unusual spin nature. Demonstration of the
      helical electron transport is a crucial step to both physics and device
      applications of topological insulators. Topological insulator nanowires, of which
      spin-textured surface electrons form 1D band manipulated by enclosed magnetic
      flux, offer a unique nanoscale platform to realize quantum transport of spin
      momentum locking nature. Here, we report an observation of a topologically
      protected 1D mode of surface electrons in topological insulator nanowires
      existing at only two values of half magnetic quantum flux (+/-h/2e) due to a spin
      Berry's phase (pi). The helical 1D mode is robust against disorder but fragile
      against a perpendicular magnetic field breaking-time-reversal symmetry. This
      result demonstrates a device with robust and easily accessible 1D helical
      electronic states from 3D topological insulators, a unique nanoscale electronic
      system to study topological phenomena. 

PMID- 24679126
TI  - Colorectal cancer in patients seen at the teaching hospitals of Guadeloupe and
      Martinique: discrepancies, similarities in clinicopathological features, and p53
      status.
AB  - BACKGROUND: In Guadeloupe and Martinique, two French Overseas Departments,
      colorectal cancer (CRC) has become an essential public health issue. However,
      little is known about CRC characteristics and the p53 status in these
      populations, particularly in Guadeloupe, whereas certification of a cancer
      registry has been recently validated. METHODS: This was a descriptive
      retrospective study of 201 patients who, between 1995 and 2000, underwent surgery
      for CRC in the Guadeloupe Teaching Hospital (GlpeTH; 83 patients) and in the
      Martinique Teaching Hospital (MqueTH; 118 patients). The clinicopathological
      features and the p53 expression, evaluated with immunohistochemistry, were
      compared at the time of diagnosis. A relationship between these parameters and
      the p53 expression was also studied. Data were analysed, using the SPSS computer
      software version 17.0. RESULTS: No statistical difference was found between the
      two groups of patients regarding age (p = 0.60), percentage of young patients
      (<=50 years; p = 0.94)), sex (p = 0.47), histological type (p = 0.073) and tumour
      sites (p = 0.65), although the GlpeTH patients were diagnosed with more distal
      colon cancers (54.2%) than the Mque TH patients (47.4%). By contrast, a
      significant difference was found regarding the tumour grade (p < 0.0001), the
      pTNM stage (p = 0.045) and the pT stage (p < 0.0001). Regarding p53 expression,
      solely for the MqueTH patients, nuclear expression was associated with pTNM, the
      percentage of p53 negative tumours increasing with the progression of the pTNM
      stages (p = 0.029). CONCLUSIONS: For the first time, this study reveals
      discrepancies in clinicopathological features and in the p53 status between the
      two groups of patients. The GlpeTH patients were diagnosed with more moderated
      CRCs but with few CRCs at pTNM IV stage. By contrast, the MqueTH patients were
      diagnosed with more differentiated tumours, but with many more CRCs at pTNM IV
      stage. This paradox may be due to differences in tumour location (distal vs
      proximal), multiplicity of the genetic profiles of patients, or patients getting
      treatment elsewhere. Although our study is limited due to its small size, it
      emphasizes the originality of our results.

PMID- 24679124
TI  - Signaling pathway cross talk in Alzheimer's disease.
AB  - Numerous studies suggest energy failure and accumulative intracellular waste play
      a causal role in the pathogenesis of several neurodegenerative disorders and
      Alzheimer's disease (AD) in particular. AD is characterized by extracellular
      amyloid deposits, intracellular neurofibrillary tangles, cholinergic deficits,
      synaptic loss, inflammation and extensive oxidative stress. These pathobiological
      changes are accompanied by significant behavioral, motor, and cognitive
      impairment leading to accelerated mortality. Currently, the potential role of
      several metabolic pathways associated with AD, including Wnt signaling, 5'
      adenosine monophosphate-activated protein kinase (AMPK), mammalian target of
      rapamycin (mTOR), Sirtuin 1 (Sirt1, silent mating-type information regulator 2
      homolog 1), and peroxisome proliferator-activated receptor gamma co-activator 1
      alpha (PGC-1alpha) have widened, with recent discoveries that they are able to
      modulate several pathological events in AD. These include reduction of amyloid
      beta aggregation and inflammation, regulation of mitochondrial dynamics, and
      increased availability of neuronal energy. This review aims to highlight the
      involvement of these new set of signaling pathways, which we have collectively
      termed "anti-ageing pathways", for their potentiality in multi-target therapies
      against AD where cellular metabolic processes are severely impaired. 

PMID- 24679127
TI  - Effectiveness of cognitive behavior therapy for severe mood disorders in an acute
      psychiatric naturalistic setting: a benchmarking study.
AB  - The current study examined the effectiveness of brief cognitive behavior therapy
      (CBT) for severe mood disorders in an acute naturalistic setting. The sample
      included 951 individuals with either major depressive disorder (n = 857) or
      bipolar disorder with depressed mood (n = 94). Participants completed a battery
      of self-report measures assessing depression, overall well-being, and a range of
      secondary outcomes both before and after treatment. We found significant
      reductions in depressive symptoms, worry, self-harm, emotional lability, and
      substance abuse, as well as significant improvements in well-being and
      interpersonal relationships, post-treatment. Comparable to outpatient studies,
      30% of the sample evidenced recovery from depression. Comparison of findings to
      benchmark studies indicated that, although the current sample started treatment
      with severe depressive symptoms and were in treatment for average of only 10
      days, the overall magnitude of symptom improvement was similar to that of
      randomized controlled trials. Limitations of the study include a lack of control
      group, a limitation of most naturalistic studies. These findings indicate that
      interventions developed in controlled research settings on the efficacy of CBT
      can be transported to naturalistic, "real world" settings, and that brief CBT
      delivered in a partial hospital program is effective for many patients with
      severe depressive symptoms.

PMID- 24679128
TI  - Differentiating levels of cognitive functioning: a comparison of the Brief
      Interview for Mental Status (BIMS) and the Brief Cognitive Assessment Tool (BCAT)
      in a nursing home sample.
AB  - OBJECTIVES: In US nursing homes, cognitive assessment has been an essential
      component of the federally mandated Minimum Data Set assessment system, inclusive
      of the Brief Interview for Mental Status (BIMS) for identifying possible
      cognitive impairment. We compare it with the Brief Cognitive Assessment Tool
      (BCAT) to determine which instrument is more sensitive in differentiating degrees
      of cognitive functioning in nursing home residents. We attempt to cross-validate
      the psychometric properties of both measures. METHOD: Two hundred twenty-nine
      individuals residing in a Maryland skilled nursing facility were referred for
      neurocognitive evaluation over a 10-month period. One hundred eighty-nine of
      these residents met inclusion criteria by completing the BCAT and BIMS, and were
      aged 60 or older. RESULTS: The BIMS and the BCAT were confirmed to have strong
      internal consistency reliability and construct validity. Both cognitive tools
      were found to predict cognitive diagnoses generally, but only the BCAT was able
      to identify residents at all specific cognitive levels. The BIMS did not
      differentiate between residents with normal cognition and those with mild
      cognitive impairment, or between mild and moderate dementia. Both measures
      demonstrated high specificity and positive predictive values for identifying
      severe cognitive impairment or probable dementia. The BIMS had lower sensitivity
      and negative predictive values for identifying dementia compared to the BCAT. The
      BCAT accounted for an additional 47% of the variance in dementia diagnoses over
      and above BIMS scores. CONCLUSION: Based on these findings, the BCAT appears to
      be more sensitive than the BIMS in predicting cognitive level for nursing home
      residents.

PMID- 24679130
TI  - Guest-effected spin-crossover in a novel three-dimensional self-penetrating
      coordination polymer with permanent porosity.
AB  - Porous and nonporous 3D heterobimetallic coordination polymers based on the 1,4
      di(pyridin-4-yl)benzene ligand (dpb), [Fe(dpb){Ag(CN)2}{Ag2(CN)3}].nSolv
      (1.nSolv; nSolv = DMF.EtOH, 2DMF.MeCN) and [Fe(dpb)2{Ag(CN)2}2] (2), have been
      synthesized by diffusion technique, respectively. Single-crystal X-ray analysis
      shows that 1.nSolv consists of a 3D self-penetrating network with in-situ
      generated [Ag2(CN)3](-) species and displays one of the largest volume values of
      porosity (299 A(3) per iron atom) after desolvation for the Hoffman-like porous
      SCO coordination polymers to date. In contrast, nonporous compound 2 is composed
      of two independent interpenetrated 3D nets with in-situ-generated [Ag(dpb)(CN)2](
      ) species. Their significant distinctions of structural architectures lead to
      dramatically different magnetic properties: 1.nSolv displays two-step guest
      effected SCO with hysteresis, whereas 2 presents characteristic paramagnetic
      behavior. 

PMID- 24679129
TI  - Effect of recombinant ADAMTS-13 on microthrombosis and brain injury after
      experimental subarachnoid hemorrhage.
AB  - BACKGROUND: A common complication after aneurysmal subarachnoid hemorrhage (SAH)
      is delayed cerebral ischemia (DCI), which is associated with vasospasm and other
      mechanisms such as microthrombosis. ADAMTS-13 activity plays a role in the
      prevention of thrombus formation in the cerebral microvasculature. Previously, we
      observed that patients with DCI have lower levels of ADAMTS-13. OBJECTIVES: To
      examine whether recombinant human ADAMTS-13 (rADAMTS-13) reduces cerebral
      microthrombus formation and brain injury in an experimental mouse model of SAH
      including wild-type and ADAMTS-13(-/-) mice. METHODS: Experimental SAH was
      induced with the prechiasmatic blood injection model. The following experimental
      groups were investigated: (i) C57BL/6J mice (n = 10); (ii) C57BL/6J mice (n = 10)
      treated with rADAMTS-13 20 min after SAH; (iii) ADAMTS-13(-/-) mice (n = 10); and
      (iv) ADAMTS-13(-/-) mice (n = 10) treated with rADAMTS-13 20 min after SAH. Mice
      were killed at 48 h. Results are presented as means with standard errors of the
      mean. RESULTS: Infusion with rADAMTS-13 reduced the extent of microthrombosis by
      ~ 50% in both wild-type mice (mean fibrinogen area: 0.28% +/- 0.09% vs. 0.15% +/-
      0.04%; P = 0.20) and ADAMTS-13(-/-) mice (mean fibrinogen area: 0.32% +/- 0.05%
      vs. 0.16% +/- 0.03%; P = 0.016). In addition, rADAMTS-13 reduced brain injury by
      > 60% in both wild-type mice (mean microglia area: 0.65% +/- 0.18% vs. 0.18% +/-
      0.04%; P = 0.013) and ADAMTS-13(-/-) mice (mean microglia area: 1.24% +/- 0.36%
      vs. 0.42% +/- 0.13%; P = 0.077). CONCLUSIONS: Our results support the further
      study of rADAMTS-13 as a treatment option for the prevention of microthrombosis
      and brain injury after SAH.

PMID- 24679132
TI  - Isomer-specific product detection of gas-phase xylyl radical rearrangement and
      decomposition using VUV synchrotron photoionization.
AB  - Xylyl radicals are intermediates in combustion processes since their parent
      molecules, xylenes, are present as fuel additives. In this study we report on the
      photoelectron spectra of the three isomeric xylyl radicals and the subsequent
      decomposition reactions of the o-xylyl radical, generated in a tubular reactor
      and probed by mass selected threshold photoelectron spectroscopy and VUV
      synchrotron radiation. Franck-Condon simulations are applied to augment the
      assignment of elusive species. Below 1000 K, o-xylyl radicals decompose by
      hydrogen atom loss to form closed-shell o-xylylene, which equilibrates with
      benzocyclobutene. At higher temperatures relevant to combustion engines, o
      xylylene generates styrene in a multistep rearrangement, whereas the p-xylylene
      isomer is thermally stable, a key point of difference in the combustion of these
      two isomeric fuels. Another striking result is that all three xylyl isomers can
      generate p-xylylene upon decomposition. In addition to C8H8 isomers,
      phenylacetylene and traces of benzocyclobutadiene are observed and identified as
      further reaction products of o-xylylene, while there is also some preliminary
      evidence for benzene and benzyne formation. The experimental results reported
      here are complemented by a comprehensive theoretical C8H8 potential energy
      surface, which together with the spectroscopic assignments can explain the
      complex high-temperature chemistry of o-xylyl radicals. 

PMID- 24679131
TI  - A pharmacist-led follow-up program for patients with coronary heart disease in
      North Norway--a qualitative study exploring patient experiences.
AB  - BACKGROUND: Coronary heart disease (CHD) is one of the leading causes of death
      worldwide. Scientific literature shows that prevention of CHD is inadequate. The
      clinical pharmacist's role in patient-centred care has been shown favourable in a
      large amount of studies, also in relation to reduction of risk factors related to
      CHD. We developed and piloted a pharmacist-led follow-up program for patients
      with established CHD after hospital discharge from a hospital in North Norway.
      The aim of the present study was to explore how participants in the follow-up
      program experienced the program with regard to four main topics; medication
      knowledge, feeling of safety and comfort with medications, the functionality of
      the program and the clinical pharmacist's role in the interdisciplinary team.
      METHODS: We performed semi-structured thematic interviews with four patients
      included in the program. After verbatim transcribing, we analysed the interviews
      using "qualitative content analyses" by Graneheim and Lundman. Trial registration
      http://www.clinicaltrials.gov: NCT01131715. RESULTS: All participants appreciated
      the follow-up program because their medication knowledge had increased,
      participation had made them feel safe, they were reassured about the
      appropriateness of their medications, and they had become more involved in their
      own medication. The participants reported that the program was well structured
      and the clinical pharmacist was said to be an important caretaker in the health
      care system. The importance of collaboration between pharmacists and physicians,
      both in hospital and primary care, was emphasized. CONCLUSION: Our results
      indicate that the follow-up program was highly appreciated among the four
      participants included in this study. The results must be interpreted in the
      context of the health care system in Norway today. Here, few pharmacists are
      working in hospitals or in close relation to the general practitioners. In
      addition, physicians are short of time in order to supply appropriate medication
      information, both in hospital and primary care. Involving pharmacists in follow
      up of patients with CHD seems to be highly appreciated among patients and may be
      a step towards improving patient care. The study is limited by the low number of
      participants.

PMID- 24679133
TI  - Use of a gentamicin-impregnated collagen sheet (Collatamp((r))) in the management
      of major soft tissue complications in pediatric cochlear implants.
AB  - OBJECTIVE AND IMPORTANCE: The objective was to report the effectiveness of
      salvage treatment in soft tissue infection around cochlear implants with an
      absorbable gentamicin collagen sheet and a periosteum and skin rotation flaps.
      CLINICAL PRESENTATION: Three patients with cochlear implant and persistent
      surrounding soft tissue infection are included. All of them underwent antibiotic
      treatment prior to surgery without any response. INTERVENTION: In this study
      preoperative and postoperative audiograms were practiced. Surgical excision of
      infectious skin and a periosteum and skin rotation flaps were performed. The
      cochlear implant was refixed in the temporal bone and a gentamicin-impregnated
      collagen sheet was located covering the cochlear implant. CONCLUSION: headings In
      all patients with soft tissue infection around the cochlear implant, infection
      was completely resolved. It was not necessary to remove the device in any case.
      The use of an absorbable gentamicin-impregnated collagen sheet is not described
      for the management of soft tissue complications in pediatric cochlear implant
      patients. The local application of high concentrations of antibiotic administered
      by this sheet may be effective against resistant bacteria and, in conjunction
      with surgery, may resolve this type of complications.

PMID- 24679135
TI  - Cost-effectiveness analysis of pneumococcal conjugate vaccine 13-valent in older
      adults in Colombia.
AB  - BACKGROUND: Nowadays, there are two vaccination strategies in Colombia to prevent
      pneumococcal diseases in people over 50 years. Our aim is to estimate cost
      effectiveness of pneumococcal conjugate vaccine 13-valent (PCV13) versus
      pneumococcal polysaccharide vaccine 23-valent (PPSV23) to prevent pneumococcal
      diseases and their related mortality in people over 50 years old in Colombia.
      METHODS: A Markov model was developed with national data, including pneumococcal
      serotypes distribution in Colombia between 2005 and 2010. Vaccination of a cohort
      was simulated and a five year time horizon was assumed. Analysis was done from a
      perspective of a third party payer. Direct costs were provided by a national
      insurance company; sensitive univariate and probabilistic analysis were done for
      epidemiological and clinical effectiveness parameters and costs. RESULTS: PCV13
      avoids 3 560 deaths by pneumococcal infections versus PPSV23 and 4 255 deaths
      versus no vaccine. PCV13 prevents 79 633 cases by all-cause pneumonia versus
      PPSV23 and 81 468 cases versus no vaccine. Total costs (healthcare and vaccines
      costs) with PCV13 would be U.S. $ 97,587,113 cheaper than PPSV23 and it would
      save U.S. $ 145,196,578 versus no vaccine. CONCLUSION: PCV13 would be a cost
      saving strategy in the context of a mass vaccination program in Colombia to
      people over 50 years old because it would reduce burden of disease and specific
      mortality by pneumococcal diseases, besides, it saves money versus PPSV23.

PMID- 24679134
TI  - Bringing the heavy: carbon ion therapy in the radiobiological and clinical
      context.
AB  - Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to
      the use of heavier ion species. For a plethora of malignancies, current
      radiotherapy using photons or protons yields marginal benefits in local control
      and survival. One hypothesis is that these malignancies have acquired, or are
      inherently radioresistant to low LET radiation. In the last decade, carbon ion
      radiotherapy facilities have slowly been constructed in Europe and Asia,
      demonstrating favorable results for many of the malignancies that do poorly with
      conventional radiotherapy. However, from a radiobiological perspective, much of
      how this modality works in overcoming radioresistance, and extending local
      control and survival are not yet fully understood. In this review, we will
      explain from a radiobiological perspective how carbon ion radiotherapy can
      overcome the classical and recently postulated contributors of radioresistance
      (alpha/beta ratio, hypoxia, cell proliferation, the tumor microenvironment and
      metabolism, and cancer stem cells). Furthermore, we will make recommendations on
      the important factors to consider, such as anatomical location, in the future
      design and implementation of clinical trials. With the existing data available we
      believe that the expansion of carbon ion facilities into the United States is
      warranted. 

PMID- 24679137
TI  - Fatal Fusarium solani infection after stem cell transplant for aplastic anemia.
AB  - Fusarium is a saprophytic and opportunistic pathogen that can cause local tissue
      infection and life-threatening systemic infection. Systemic infection is rare and
      is observed primarily in immunocompromised patients. The early diagnosis is
      difficult, and the optimal treatment is unclear. However, the mortality is high.
      A 21-year-old man with aplastic anemia was treated with an allogeneic stem cell
      transplant. He developed fatal Fusarium solani infection. Fusarium species may be
      overlooked pathogenic fungi in immunocompromised patients, especially bone marrow
      transplant recipients. 

PMID- 24679136
TI  - Measurement invariance of the depressive symptoms scale during adolescence.
AB  - BACKGROUND: This study examined (1) the factor structure of a depressive symptoms
      scale (DSS), (2) the sex and longitudinal invariance of the DSS, and (3) the
      predictive validity of the DSS scale during adolescence in terms of predicting
      depression and anxiety symptoms in early adulthood. METHODS: Data were drawn from
      the Nicotine Dependence in Teens (NDIT) study, an ongoing prospective cohort
      study of 1,293 adolescents. RESULTS: The analytical sample included 527
      participants who provided complete data or had minimal missing data over follow
      up. Confirmatory factor analysis revealed that an intercorrelated three-factor
      model with somatic, depressive, and anxiety factors provided the best fit.
      Further, this model was invariant across sex and time. Finally, DSS scores at
      Time 3 correlated significantly with depressive and anxiety symptoms measured at
      Time 4. CONCLUSIONS: Results suggest that the DSS is multidimensional and that it
      is a suitable instrument to examine sex differences in somatic, depressive, and
      anxiety symptoms, as well as changes in these symptoms over time in adolescents.
      In addition, it could be used to identify individuals at-risk of psychopathology
      during early adulthood.

PMID- 24679138
TI  - Determination of non-opioid analgesics in adulterated food and dietary
      supplements by LC-MS/MS.
AB  - Commercially available non-opioid analgesics such as acetaminophen and non
      steroidal anti-inflammatory drugs (NSAIDs) have been used to adulterate some
      foods and dietary supplements. Considering the rapid growth of the dietary
      supplement market, it is essential to analyse various analgesics used for
      adulteration over a time period. Acetaminophen and 16 NSAIDs used to adulterate
      food and dietary supplements were simultaneously determined by LC-MS/MS. The
      method was validated by determining the coefficient of determinations, limit of
      quantification and recovery, and samples were analysed for the determination of
      analgesics. Consequently, acetaminophen, diclofenac, ibuprofen, indomethacin,
      naproxen and piroxicam were detected in 53 samples (n = 214). Ibuprofen was the
      most commonly used adulterant, which was detected in a wide concentration range
      (1.06-233.40 mg g(-1)) and was present in about one-third of the adulterated
      samples. Various types of samples, in particular pills and capsules (73.6% of the
      total positive samples), were found to be adulterated with non-opioid analgesics.
      Samples containing high concentrations of analgesics can have a deleterious
      effect on human health, and thus the continued monitoring of adulterated food and
      dietary supplements is essential to maintain a healthy life.

PMID- 24679139
TI  - Response to comment on "Electrolytic manipulation of persulfate reactivity by
      iron electrodes for TCE degradation in groundwater".

PMID- 24679140
TI  - Ultrastructural features of neuroblastic tumours in relation to morphological,
      and molecular findings; a retrospective review study.
AB  - BACKGROUND: Neuroblastoma is the most common solid tumour of infancy and is
      responsible for 15% of childhood cancer deaths. Presence of amplified MYCN in
      neuroblastoma is associated with poor prognosis and rapid tumour progression. The
      aim of this study was to examine and compare the ultrastructural features of high
      risk MYCN amplified neuroblastomas, with lower-risk non-MYCN amplified tumours.
      METHODS: This was a retrospective study evaluating archival diagnostic tissue
      samples, in which Fluorescence in-situ hybridisation (FISH) had been used at
      diagnosis to establish MYCN status. 22 (11 MYCN amplified tumours and 11 non-MYCN
      amplified) tumours of similar light microscopic appearance (poorly differentiated
      neuroblastoma) were then selected for ultrastructural examination. RESULTS: There
      is a relationship between ultrastructural features in neuroblastoma and MYCN
      status, although with marked overlap between groups. MYCN amplified tumours
      generally exhibited a 'less differentiated' ultrastructural phenotype, with
      significantly smaller neurotubules (NT) in the cell body (p < 0.002). Non-MYCN
      amplified tumours show increased features of neuronal differentiation, with fewer
      neurosecretory granules (NSG) and NT in the cytoplasm. CONCLUSIONS: MYCN
      amplification is associated with a less differentiated ultrastructural phenotype,
      and lack of MYCN amplification with relative ultrastructural neuronal
      differentiation.

PMID- 24679141
TI  - Exploring the relationships among humility, negative interaction in the church,
      and depressed affect.
AB  - OBJECTIVE: The purpose of this study is to test three hypotheses involving
      humility. The first hypothesis specifies that people who are more deeply involved
      in religion will be more humble than individuals who are not as involved in
      religion. The second hypothesis predicts that humility will offset the effects of
      negative interaction in the church on depressed affect scores. The third
      hypothesis specifies that there will be a positive relationship between age and
      humility. METHODS: The data come from the Religion, Aging, and Health Survey, a
      nationwide survey of middle-aged and older Christians who attend church on a
      regular basis (N = 1154). RESULTS: The findings suggest that people who are more
      committed to their faith tend to be more humble. The results also reveal that
      negative interaction in the church is greater for people with lower humility
      scores than individuals with higher humility scores. In contrast, the data
      indicate that older adults are not more humble than middle-aged people.
      CONCLUSIONS: The findings are noteworthy because they identify a source of
      resilience that may help middle-aged and older adults cope more effectively with
      the effects of stress.

PMID- 24679142
TI  - Pyrolysis of cellulose under ammonia leads to nitrogen-doped nanoporous carbon
      generated through methane formation.
AB  - Here, we present a simple one-step fabrication methodology for nitrogen-doped (N
      doped) nanoporous carbon membranes via annealing cellulose filter paper under
      NH3. We found that nitrogen doping (up to 10.3 at %) occurs during cellulose
      pyrolysis under NH3 at as low as 550  degrees C. At 700  degrees C or above, N
      doped carbon further reacts with NH3, resulting in a large surface area (up to
      1973.3 m(2)/g). We discovered that the doped nitrogen, in fact, plays an
      important role in the reaction, leading to carbon gasification. CH4 was
      experimentally detected by mass spectrometry as a product in the reaction between
      N-doped carbon and NH3. When compared to conventional activated carbon (1533.6
      m(2)/g), the N-doped nanoporous carbon (1326.5 m(2)/g) exhibits more than double
      the unit area capacitance (90 vs 41 mF/m(2)). 

PMID- 24679144
TI  - Improving of catalase stability properties by encapsulation in alginate/Fe3O4
      magnetic composite beads for enzymatic removal of H2O2.
AB  - The aim of this study was enhancing of stability properties of catalase enzyme by
      encapsulation in alginate/nanomagnetic beads. Amounts of carrier (10-100 mg) and
      enzyme concentrations (0.25-1.5 mg/mL) were analyzed to optimize immobilization
      conditions. Also, the optimum temperature (25-50 degrees C), optimum pH (3.0
      8.0), kinetic parameters, thermal stability (20-70 degrees C), pH stability (4.0
      9.0) operational stability (0-390 min), and reusability were investigated for
      characterization of the immobilized catalase system. The optimum pH levels of
      both free and immobilized catalase were 7.0. At the thermal stability studies,
      the magnetic catalase beads protected 90% activity, while free catalase
      maintained only 10% activity at 70 degrees C. The thermal profile of magnetic
      catalase beads was spread over a large area. Similarly, this system indicated the
      improving of the pH stability. The reusability, which is especially important for
      industrial applications, was also determined. Thus, the activity analysis was
      done 50 times in succession. Catalase encapsulated magnetic alginate beads
      protected 83% activity after 50 cycles. 

PMID- 24679143
TI  - Vulnerability-specific stress generation: an examination of depressogenic
      cognitive vulnerability across multiple domains.
AB  - BACKGROUND AND OBJECTIVES: Although there is supporting evidence for the stress
      generation hypothesis (i.e., the tendency for depression-prone individuals to
      experience more negative dependent events influenced by their behaviors and
      characteristics), additional research is required to advance current
      understanding of the specific types of dependent events relevant to this effect.
      The present study elaborated on the stress generation hypothesis, in which the
      content of negative dependent events experienced by individuals is contingent
      upon, and matches, the nature of their particular vulnerabilities. This extension
      was tested within the context of Cole's competency-based model of depression.
      DESIGN: Participants (n=185) were assessed at two time-points separated by a four
      month interval. METHODS: Self-perceived competence in academic, social, and
      appearance domains at the initial time-point were examined in relation to
      negative life events prospectively occurring over the four-month follow-up
      period, assessed using the "contextual threat" method. RESULTS: Partial support
      was obtained for vulnerability-specific stress generation. Stress-generation
      specificity was found for self-perceived competence in appearance and academic
      domains, but not for self-perceived social competence. CONCLUSIONS: The current
      findings are consistent with the possibility of a more complex relation between
      self-perceived social competence and domain-congruent stress generation.
      Individuals may be more likely to experience negative dependent events in domains
      matching their specific vulnerabilities.

PMID- 24679146
TI  - Is the desire for amputation related to disturbed emotion processing? A multiple
      case study analysis in BIID.
AB  - Body integrity identity disorder (BIID) is characterized by the overwhelming
      desire to amputate one or more healthy limbs or to be paraplegic. Recently, a
      neurological explanation of this condition has been proposed, in part on the
      basis of findings that the insular cortex might present structural anomalies in
      these individuals. While these studies focused on body representation, much less
      is known about emotional processing. Importantly, emotional impairments have been
      found in psychiatric disorders, and a psychiatric etiology is still a valid
      alternative to purely neurological accounts of BIID. In this study, we explored,
      by means of a computerized experiment, facial emotion recognition and emotional
      responses to disgusting images in seven individuals with BIID, taking into
      account their clinical features and investigating in detail disgust processing,
      strongly linked to insular functioning. We demonstrate that BIID is not
      characterized by a general emotional impairment; rather, there is a selectively
      reduced disgust response to violations of the body envelope. Taken together, our
      results support the need to explore this condition under an interdisciplinary
      perspective, taking into account also emotional connotations and the social
      modulation of body representation. 

PMID- 24679147
TI  - The role of post-operative imaging in cochlear implant surgery: a review of 220
      adult cases.
AB  - OBJECTIVES: To determine the incidence of abnormal radiological findings after
      cochlear implantation and their effect on clinical outcomes. METHODS:
      Retrospective review of 220 adult cochlear implants. Clinical records and post
      operative plain X-rays were reviewed and compared with pre-operative and 6-month
      post-operative City University of New York (CUNY) speech scores. RESULTS: There
      were no cases of extra-cochlear array misplacement. Imaging showed 20 cases of
      incomplete array insertion (9.2%), 3 cases of kinking of the array (1.4%), 2
      cases of tip rollover (0.9%), and 1 case of apparent array fracture (0.5%).
      Patient management was not altered by abnormal imaging. Patients with abnormal
      radiological findings had slightly minor improvements (median 39 vs. 56%) in City
      University of New York (CUNY) speech discrimination scores at 6 months (Mann
      Whitney U test, P = 0.043). CONCLUSION: All abnormalities on post-operative
      imaging were minor and did not alter patient management. The future role of post
      operative imaging is discussed.

PMID- 24679148
TI  - Rb2CdBr2I2: a new IR nonlinear optical material with a large laser damage
      threshold.
AB  - This paper describes the synthesis, crystal structure, and photophysical
      properties of a new compound Rb2CdBr2I2. It crystallizes in the
      noncentrosymmetric space group Ama2. In the crystal, all the distorted
      tetrahedron [CdBr2I2](2-) groups are arranged in a way such that all the Cd-I
      bonds are located in the same side of the Cd atoms resulting in a net
      polarization. Rb2CdBr2I2 showed a powder second harmonic generation (SHG)
      response 4 times that of KH2PO4 (KDP). The preliminary measurement indicated that
      it exhibits a large laser-induced damage threshold (LDT) of 190 MW/cm(2) which is
      6 times that of AgGaS2. It also exhibits a wide transparent region (0.37-14 MUm)
      with a relatively high (up to 490  degrees C) thermal stability. All these
      indicate that Rb2CdBr2I2 is a new promising candidate for NLO materials in the IR
      region. 

PMID- 24679151
TI  - Solid-phase synthesis of P-boronated oligonucleotides by the H-boranophosphonate
      method.
AB  - Recently, P-boronated oligonucleotides have been attracting much attention as
      potential therapeutic oligonucleotides. In this study, we developed H
      boranophosphonate oligonucleotide bearing a borano group and hydrogen atom on the
      internucleotidic phosphorus and demonstrated that this novel P-boronated
      oligonucleotide is a versatile precursor to various P-boronated oligonucleotides
      such as boranophosphate, boranophosphorothioate, and boranophosphoramidate. The
      method was also applicable to the synthesis of a locked nucleic acid-modified
      boranophosphate oligonucleotide, which exhibited a dramatically enhanced affinity
      to complementary oligonucleotides.

PMID- 24679150
TI  - Complete structural elucidation of an oxidized polysialic acid drug intermediate
      by nuclear magnetic resonance spectroscopy.
AB  - Polysialic acid (PSA) is a high molecular weight glycan composed of repeat units
      of alpha(2->8) linked 5-N-acetyl-neuraminic acid. Mild periodate oxidation of PSA
      selectively targets the end sialic acid ring containing three adjacent alcohols
      generating a putative aldehyde, which can be used for terminal attachment of PSA
      to therapeutic proteins. The work presented here permitted complete NMR peak
      assignments of not only the repeat units, but also the two terminal units at each
      end of oxidized PSA, an intermediate, which can be used to improve drug
      performance. The assignments were made using a variety of NMR techniques on
      oligomers of sialic acid as well as oxidized PSA with molecular masses of 4 and
      20 kDa. This enabled structure elucidation that showed the actual moiety formed
      was not the expected aldehyde or its hydrate, but is a hemiacetal between the
      oxidation site on the terminal sialic acid ring and the penultimate ring. The
      existence of a hemiacetal structure has major implications on stability,
      reactivity, and conjugation chemistry of oxidized PSA. The assignment process
      also revealed deuterium exchange of the axial hydrogen at the 3- (methylene)
      position of the ring, which was in agreement with the literature. 

PMID- 24679149
TI  - Who children spend time with after school: associations with objectively recorded
      indoor and outdoor physical activity.
AB  - BACKGROUND: Understanding how the determinants of behaviour vary by context may
      support the design of interventions aiming to increase physical activity. Such
      factors include independent mobility, time outdoors and the availability of other
      children. At present little is known about who children spend their time with
      after school, how this relates to time spent indoors or outdoors and activity in
      these locations. This study aimed to quantify who children spend their time with
      when indoors or outdoors and associations with moderate to vigorous physical
      activity (MVPA). METHODS: Participants were 427 children aged 10-11 from Bristol,
      UK. Physical activity was recorded using an accelerometer (Actigraph GT1M) and
      matched to Global Positioning System receiver (Garmin Foretrex 201) data to
      differentiate indoor and outdoor location. Children self-reported who they spent
      time with after school until bed-time using a diary. Each 10 second epoch was
      coded as indoors or outdoors and for 'who with' (alone, friend, brother/sister,
      mum/dad, other grown-up) creating 10 possible physical activity contexts. Time
      spent and MVPA were summarised for each context. Associations between time spent
      in the different contexts and MVPA were examined using multiple linear regression
      adjusting for daylight, age, deprivation and standardised body mass index.
      RESULTS: During the after school period, children were most often with their
      mum/dad or alone, especially when indoors. When outdoors more time was spent with
      friends (girls: 32.1%; boys: 28.6%) than other people or alone. Regression
      analyses suggested hours outdoors with friends were positively associated with
      minutes of MVPA for girls (beta-coefficient [95% CI]: 17.4 [4.47, 30.24]) and
      boys (17.53 [2.76, 32.31]). Being outdoors with brother/sister was associated
      with MVPA for girls (21.2 [14.17, 28.25]) but not boys. Weaker associations were
      observed for time indoors with friends (girls: 4.61 [1.37, 7.85]; boys: (7.42
      [2.99, 11.85]) and other adults (girls: 5.33 [2.95, 7.71]; boys: (4.44 [1.98,
      6.90]). Time spent alone was not associated with MVPA regardless of gender or
      indoor/outdoor location. CONCLUSIONS: Time spent outdoors with other children is
      an important source of MVPA after school. Interventions to increase physical
      activity may benefit from fostering friendship groups and limiting the time
      children spend alone.

PMID- 24679145
TI  - Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the
      STEPH community-based study.
AB  - BACKGROUND: The incidence of superficial vein thrombosis (SVT) in the general
      adult population remains unknown. OBJECTIVES: To assess the annual diagnosis rate
      of symptomatic, objectively confirmed lower limb SVT, associated or not with
      concomitant deep vein thrombosis and/or symptomatic pulmonary embolism.
      METHODS/PATIENTS: We conducted, from November 14, 2011, to November 13, 2012, a
      multicenter, community-based study in the Saint-Etienne urban area, France,
      representing a population of 265 687 adult residents (according to the 2009
      census). All 248 general practitioners located within the area were asked to
      refer any patient with clinically suspected lower limb acute SVT to a vascular
      physician for systematic compression ultrasonography. All 28 vascular physicians
      located within the area participated in the study. The annual diagnosis rate,
      with the corresponding 95% confidence interval (CI), was calculated as the number
      of patients with symptomatic, objectively confirmed SVT divided by the number of
      person-years at risk defined by population data of the area. All venous
      thromboembolic events were validated by an independent central adjudication
      committee. RESULTS: Overall, 171 patients with symptomatic, confirmed SVT were
      reported. The annual diagnosis rate was 0.64& (95% CI, 0.55%-0.74&), was higher
      in women, and increased with advancing age regardless of gender [corrected].
      Concomitant deep vein thrombosis (20 proximal) was observed in 42 patients (24.6%
      [95% CI, 18.3%-31.7%]), and concomitant symptomatic pulmonary embolism was
      observed in eight patients (4.7% [95% CI, 2.0%-9.0%]). CONCLUSIONS: This first
      community-based study showed that symptomatic SVT with confirmed diagnosis is a
      relatively common disease frequently associated with thromboembolic events in the
      deep venous system.

PMID- 24679152
TI  - Cellular Lipid Composition Affects Sensitivity of Plant Pathogens to Fengycin, an
      Antifungal Compound Produced by Bacillus subtilis Strain CU12.
AB  - Fengycin is an antimicrobial cyclic lipopeptide produced by various Bacillus
      subtilis strains, including strain CU12. Direct effects of fengycin include
      membrane pore formation and efflux of cellular contents leading to cell death in
      sensitive microorganisms. In this study, four plant pathogens were studied in
      order to elucidate the role of membrane lipids in their relative sensitivity to
      fengycin. Inhibition of mycelial growth in these pathogens varied considerably.
      Analysis of membrane lipids in these microorganisms indicated that sensitivity
      correlated with low ergosterol content and shorter phospholipid fatty acyl
      chains. Sensitivity to fengycin also correlated with a lower anionic/zwitterionic
      phospholipid ratio. Our data suggest that decreased fluidity buffering capacity,
      as a result of low ergosterol content, and higher intrinsic fluidity afforded by
      short fatty acyl chain length may increase the sensitivity of microbial membranes
      to fengycin. Our results also suggest that lower content in anionic phospholipids
      may increase fengycin insertion into the membrane through reduced electrostatic
      repulsion with the negatively charged fengycin. The intrinsic membrane lipid
      composition may contribute, in part, to the observed level of antimicrobial
      activity of fengycin in various plant pathogens.

PMID- 24679153
TI  - A Tripartite Interaction Between Spartina alterniflora, Fusarium palustre, and
      the Purple Marsh Crab (Sesarma reticulatum) Contributes to Sudden Vegetation
      Dieback of Salt Marshes in New England.
AB  - Tripartite interactions are common and occur when one agent (an arthropod or
      pathogen) changes the host plant in a manner that alters the attack of the
      challenging agent. We examined herbivory from the purple marsh crab (Sesarma
      reticulatum) on Spartina alterniflora following exposure to drought or
      inoculation with Fusarium palustre in mecocosms in the greenhouse and in crab
      infested creek banks along intertidal salt marshes. Initially, drought stress on
      S. alterniflora and disease from F. palustre were examined in the greenhouse.
      Then, a second challenger, the purple marsh crab, was introduced to determine how
      drought and disease from F. palustre affected the attraction and consumption of
      S. alterniflora. Plant height and shoot and root weights were reduced in plants
      subjected to severe drought treatment when compared with normally irrigated
      plants. When the drought treatment was combined with inoculation with F.
      palustre, plants were significantly more stunted and symptomatic, had less fresh
      weight, more diseased roots, and a greater number of Fusarium colonies growing
      from the roots (P < 0.001) than noninoculated plants. The effects were additive,
      and statistical interactions were not detected between drought and inoculation.
      Estimates of herbivory (number of grass blades cut or biomass consumption) by the
      purple marsh crab were significantly greater on drought-stressed, diseased plants
      than on healthy plants irrigated normally. Drought increased attraction to the
      purple marsh crab more than inoculation with F. palustre. However, when only mild
      drought conditions were imposed, plant consumption was greater on inoculated
      plants. Healthy, nonstressed transplants set into plots in crabinfested
      intertidal creek banks were grazed less each year than inoculated plants or
      plants that were exposed to drought. Several hypotheses relating to nutrition,
      chemotaxis, and visual attraction are presented to explain how stress from
      drought or disease might favor herbivory.

PMID- 24679155
TI  - Adiponectin receptor 1 overexpression reduces lipid accumulation and hypertrophy
      in the heart of diet-induced obese mice--possible involvement of oxidative stress
      and autophagy.
AB  - BACKGROUND: Studies show that adiponectin and its receptors (AdipoR1 and 2) play
      important roles in regulating glucose and lipid metabolism in mice. Obesity, type
      II diabetes and cardiovascular disease are highly correlated with downregulated
      adiponectin signaling; however, research has not clarified the functions of
      AdipoR1 in vivo. METHODS: In this study, mice were induced to overexpress the
      AdipoR1 transgene so that its functions could be studied in relation to
      hypertrophic cardiomyopathy. Wild-type and AdipoR1-transgenic male mice were fed
      ad libitum with a standard chow diet or else a high-fat/sucrose diet (HFSD) for
      24 weeks, beginning at 6-7 weeks of age. RESULTS: After receiving the 24-week
      HFSD, AdipoR1-transgenic mice did not become obese, nor did they develop heart
      hypertrophy. The AdipoR1 transgene decreased the elevating cardiac troponin I
      expression caused by the HFSD. While the HFSD induced mRNA expression of CD36 and
      CPTI, AdipoR1 reversed it. Suppression of cardiac SOD mRNA expression by the HFSD
      was improved by the AdipoR1 transgene. The HFSD caused a higher autophagic gene
      expression of Beclin 1 and Lamp 2 A in the heart, whereas the AdipoR1 transgene
      ameliorated them. CONCLUSIONS: The AdipoR1 transgene enabled mice to resist diet
      induced obesity while decreasing lipid accumulation, oxidative stress and
      autophagic damage. These effects might contribute to the improvement of heart
      functions in diet-induced obese mice.

PMID- 24679156
TI  - Association of Raoultella bacteremia with diseases of the biliary tract.

PMID- 24679157
TI  - Direct and indirect relationships between physical activity and happiness levels
      among older adults: a cross-sectional study.
AB  - OBJECTIVES: The purposes of this study were to examine if physical activity (PA)
      is associated to happiness and to investigate if social functioning and health
      status mediate this association. METHOD: Participants of this cross-sectional
      study were 323 men and women, age 60 or over, who were covered by the medical
      insurance of the French National Education System, France. They received by mail
      a self-report questionnaire that asked for information about general health, PA,
      and happiness. RESULTS: In multinomial logistic regressions, the total volume of
      PA was associated to higher levels of happiness, but this association disappeared
      in the presence of social functioning. A structural equation modelling (SEM)
      showed an indirect association between PA and happiness, which was mediated by
      participants' health status and social functioning; in this SEM model, social
      functioning was the only variable directly associated to happiness. CONCLUSION:
      Complex associations among PA, health status, and social functioning appear to
      determine happiness levels in older adults.

PMID- 24679154
TI  - Clinical proteomic biomarkers: relevant issues on study design & technical
      considerations in biomarker development.
AB  - Biomarker research is continuously expanding in the field of clinical proteomics.
      A combination of different proteomic-based methodologies can be applied depending
      on the specific clinical context of use. Moreover, current advancements in
      proteomic analytical platforms are leading to an expansion of biomarker
      candidates that can be identified. Specifically, mass spectrometric techniques
      could provide highly valuable tools for biomarker research. Ideally, these
      advances could provide with biomarkers that are clinically applicable for disease
      diagnosis and/ or prognosis. Unfortunately, in general the biomarker candidates
      fail to be implemented in clinical decision making. To improve on this current
      situation, a well-defined study design has to be established driven by a clear
      clinical need, while several checkpoints between the different phases of
      discovery, verification and validation have to be passed in order to increase the
      probability of establishing valid biomarkers. In this review, we summarize the
      technical proteomic platforms that are available along the different stages in
      the biomarker discovery pipeline, exemplified by clinical applications in the
      field of bladder cancer biomarker research. 

PMID- 24679158
TI  - Inferior vena cava tumor thrombus after partial nephrectomy for renal cell
      carcinoma.
AB  - BACKGROUND: Partial nephrectomy is now the gold standard treatment for small
      renal tumors. Local recurrence is a major problem after partial nephrectomy, and
      local recurrence in the remnant kidney after partial nephrectomy is common. CASE
      PRESENTATION: A 77-year-old man underwent right partial nephrectomy for a T1
      right renal cell carcinoma. Microscopic examination revealed a clear cell renal
      carcinoma, grade 2, stage pT3a. Although the surgical margin was negative, the
      carcinoma invaded the perirenal fat, and vascular involvement was strongly
      positive. Thirty months after partial nephrectomy, an enhanced computed
      tomographic scan showed local recurrence of the renal cell carcinoma extending
      into the inferior vena cava without renal mass. Hence, we performed right radical
      nephrectomy and intracaval thrombectomy. Microscopic examination revealed a clear
      cell carcinoma grade 2, stage pT3a + b. The patient is still alive with no
      evidence of recurrence 10 months post-procedure. CONCLUSION: To our knowledge,
      local recurrence of renal cell carcinoma extending into the inferior vena cava
      after partial nephrectomy has not been reported in the literature. Our case
      report emphasizes the importance of strict surveillance of patients after partial
      nephrectomy, especially for those with renal cell carcinoma positive for
      microvessel involvement.

PMID- 24679160
TI  - Solid-state electrochemistry of a semiconducting MMX-type diplatinum iodide chain
      complex.
AB  - Electron-transfer-facilitated dissolution, ion insertion, and desorption
      associated with an MMX-type quasi-one-dimensional iodide-bridged dinuclear Pt
      complex (MMX chain) have been investigated for the first time.
      K2(NC3N)[Pt2(pop)4I].4H2O (1) (NC3N(2+) = (H3NC3H6NH3)(2+); pop = P2H2O5(2-)) is
      a semiconductor with a three-dimensional coordination-bond and hydrogen-bond
      network included in the chain. The cyclic voltammetry of 1 was studied by using 1
      modified electrodes in contact with acetonitrile solutions containing
      electrolyte. The chemical reversibility for oxidation of 1 depended on the
      electrolyte cation size, with large cations such as tetrabutylammonium (Bu4N(+))
      being too large to penetrate the pores formed by the loss of K(+) and NC3N(2+)
      upon oxidation. The potential for reduction of 1 decreased as the cation size
      increased. The presence of the acid induced additional well-defined processes but
      with gradual solid dissolution, attributed to the breaking of the coordination
      bond networks. 

PMID- 24679159
TI  - Higher risk of renal impairment associated with tenofovir use amongst people
      living with HIV in India: a comparative cohort analysis between Western India and
      United Kingdom.
AB  - BACKGROUND: Data on the renal safety of Tenofovir (TDF) in Low and Middle Income
      Countries (LMICs) is scarce. We compared development of various forms of renal
      impairment with use of TDF-containing antiretroviral therapy (ART) between a
      cohort from the Institute of Infectious Diseases (IID) Pune, Western India and
      the Royal Free Hospital (RFH) London, UK. METHODS: This is a retrospective
      analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and
      24 months post TDF initiation using the Modification of Diet in Renal Disease
      (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with
      pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated
      with progression to eGFR < 60 ml/min/1.73 m2 were calculated using standard
      survival methods. RESULTS: A total of 574 (59% Caucasian) at the RFH, and 708
      (100% Indian ethnicity) PLHIV from IID were included. Baseline median eGFR were
      similar; RFH 102 (IQR 89, 117), IID 100 (82, 119). At 24 months, mean (SD)
      decline in eGFR was -7(21) at RFH (p < 0.0001) and -7(40) at IID (p = 0.001).
      Amongst those with pre-TDF eGFR > 90 ml/min/1.73 m2 PLHIV at IID were more likely
      to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001)
      and had a faster rate of progression estimated using Kaplan Meier methods. Risk
      factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and
      receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4
      [1.2, 4.8] p = 0.01). CONCLUSIONS: There is higher frequency of treatment
      limiting renal impairment events amongst PLHIV receiving TDF in Western India. As
      TDF scale up progresses, programs need to develop capacity for monitoring and
      treatment of renal impairment associated with TDF.

PMID- 24679161
TI  - Circular dichroism spectra of uridine derivatives: ChiraSac study.
AB  - The experimental circular dichroism (CD) spectra of uridine and NH2-uridine that
      were different in the intensity and shape were studied in the light of the
      ChiraSac method. The theoretical CD spectra at several different conformations
      using the symmetry-adapted-cluster configuration-interaction (SAC-CI) theory
      largely depended on the conformational angle, but those of the anti-conformers
      and the Boltzmann average reproduced the experimentally obtained CD spectra of
      both uridine and NH2-uridine. The differences in the CD spectra between the two
      uridine derivatives were analyzed by using the angle theta between the electric
      transition dipole moment (ETDM) and the magnetic transition dipole moment (MTDM).

PMID- 24679162
TI  - Very small embryonic-like stem cells: a scientific debate?

PMID- 24679163
TI  - Equity in human papilloma virus vaccination uptake?: sexual behaviour, knowledge
      and demographics in a cross-sectional study in (un)vaccinated girls in the
      Netherlands.
AB  - BACKGROUND: In the Netherlands, human papillomavirus (HPV) vaccination is part of
      a national program equally accessible for all girls invited for vaccination. To
      assess possible inequalities in vaccine uptake, we investigated differences
      between vaccinated and unvaccinated girls with regard to various characteristics,
      including education and ethnicity, (both associated with non-attendance to the
      national cervical screening program), sexual behaviour and knowledge of HPV.
      METHODS: In 2010, 19,939 nationwide randomly-selected 16-17 year-old girls (2009
      vaccination campaign) were invited to fill out an online questionnaire. A
      knowledge scale score and multivariable analyses identified variables associated
      with vaccination status. RESULTS: 2989 (15%) of the selected girls participated
      (65% vaccinated, 35% unvaccinated). The participants were comparable with regard
      to education, ethnicity, most sexual risk behaviour and had similar knowledge
      scores on HPV transmission and vaccination. However, unvaccinated girls lived in
      more urbanised areas and were more likely to have a religious background.
      Irrespective of vaccination status, 81% of the girls were aware of the causal
      relationship between HPV and cervical cancer, but the awareness of the necessity
      of cervical screening despite being vaccinated was limited. CONCLUSIONS: HPV
      vaccine uptake was not associated with knowledge of HPV and with factors that are
      known to be associated with non-attendance to the cervical cancer screening
      program in the Netherlands. Furthermore, most sexual behaviour was not related to
      vaccination status meaning that teenage unvaccinated girls were not at a
      disproportionally higher risk of being exposed to HPV. Routine HPV vaccination
      may reduce the social inequity of prevention of cervical cancer.

PMID- 24679164
TI  - Cobalt-catalyzed cyclization of carbon monoxide, imine, and epoxide.
AB  - Cobalt-catalyzed cyclization of CO, imine, and epoxide has been developed. A
      convenient catalyst system composed of Co2(CO)8 and LiCl is identified, and the
      substrate scope has been explored. The reaction provides an efficient method for
      the synthesis of substituted 1,3-oxazinan-4-ones. 

PMID- 24679165
TI  - Novel trends for use of microbial tannases.
AB  - Tannases, mainly produced by microorganisms, are able to hydrolyze gallotannins,
      ellagitannins, complex tannins, and gallic acid esters into gallic acid, ellagic
      acid, glucose, or alcohols, and also synthesize gallic acid esters using tannic
      acid or gallic acid with a variety of alcohols in nonaqueous media. Microbial
      tannases have been widely applied especially in beverage processing,
      pharmaceutics, and brewing. However, many factors, especially high production
      costs, severely limit the use of microbial tannases at the industrial level. In
      this minireview, we aim to provide an overview of the advances in applications of
      microbial tannases during the last 15 years, mainly including the following
      respects: hydrolysis of tea cream, modification of green tea catechins,
      production of gallic acid, debittering of fruit juices, degradation of tannery
      effluents, and synthesis of propyl gallate, trying to know the trends and
      prospects for the future in applications of microbial tannases. 

PMID- 24679167
TI  - Making the leap from daily oral dosing to long-acting injectables: lessons from
      the antipsychotics.
AB  - There are now long-acting versions of six antipsychotic drugs on the U.S. market,
      and with them, five unique combinations of molecular form and delivery strategy
      long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses
      of schizophrenia, but their introduction has been slow, taking at least nine
      years after the approval of each oral drug. Oily solutions of lipophilic prodrugs
      were the first to enter the LAIA market, but they relied on esterification of a
      hydroxyl handle that was lost with the emergence of the atypical antipsychotics.
      A review of the literature and patents shows that companies tested many different
      approaches before reaching the currently marketed versions, including aqueous
      suspensions of poorly soluble salts, polymeric microspheres, and new approaches
      to making prodrugs. Yet, very little has been published to support faster
      development of safe long-acting injectables (LAIs). This review introduces some
      of the critical considerations in creating an LAI; then it analyzes the existing
      products and discusses areas where further research is needed. The available
      literature suggests that lipophilic prodrugs may be inherently safer than poorly
      soluble salts as LAIs. Other areas needing additional study include (1) the range
      of physical properties acceptable for LAIs and the effect of prodrug tail length
      in achieving them, and (2) the role of physiological responses at the injection
      site in the release of drug from a depot.

PMID- 24679166
TI  - Survival and prognostic factors in well-differentiated pancreatic neuroendocrine
      tumors.
AB  - OBJECTIVES: Pancreatic neuroendocrine tumors (P-NETs) account for 2-3% of all
      pancreatic neoplasms. The aim of our study was to investigate survival and
      prognostic factors in patients with P-NETs. MATERIAL AND METHODS: We
      retrospectively reviewed the medical records of 114 patients diagnosed with well
      differentiated P-NETs from 1982 through 2010. We studied demographical, clinical,
      radiological, and histopathological characteristics. RESULTS: Median age at
      diagnosis was 57 years (range 32-83); 53% were men and 78% had nonfunctional
      tumors. The most common presenting symptoms were abdominal pain (41%), weight
      loss (36%), and diarrhea (25%); 19% of the tumors were incidental findings.
      Median duration of symptoms before diagnosis was 4 months, 3 months for
      nonfunctional, and 12 months for functional tumors (p < 0.001). At diagnosis,
      32.5% patients had local, 22.8% had regional, and 44.7% had distant disease. Men
      had more often distant disease at diagnosis (p = 0.02). Median survival was 6.6
      years (95% confidence interval [CI]: 4.0-9.2). Overall 5-year survival was 53.9%
      (95% CI: 43.4-63.3). For those with local disease and those with distant disease
      at diagnosis, the 5-year survivals were 70.2% (95% CI: 49.9-83.6) and 33.0% (95%
      CI: 19.7-46.7), respectively. Surgery with curative intent was performed on 46
      patients. Newly detected liver metastases were diagnosed up to 10 years after
      surgery in this group. In patients with metastases, palliative surgery
      (debulking) did not have a significant effect on survival compared to those who
      had no surgery. CONCLUSION: Distant metastases, Ki-67 > 2%, nonfunctional tumors,
      elevated level of chromogranin A, and palliative treatment were associated with
      poor survival.

PMID- 24679168
TI  - Allocentric spatial neglect with posterior cortical atrophy.
AB  - Patients with posterior cortical atrophy (PCA) have been reported to have neglect
      in the egocentric/ body-centered reference frame. This report describes a woman
      with PCA who had a right-sided stimulus-based form of allocentric visual neglect
      on cancellation, reading, and drawing tests. Her brain imaging revealed left
      parietal atrophy. The pathophysiology of this disorder may be related to an
      impairment of the ventral "what" stream's ability to interact with the dorsal
      "where" stream that mediates the allocation of spatial attention, or a deficit in
      the systems that allocate contralateral focal attention. Further research is
      needed to better understand the mechanisms of this disorder and to optimally
      treat it. 

PMID- 24679169
TI  - CD8/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer
      predicts nodal metastasis and survival.
AB  - BACKGROUND AND AIMS: Reliable prognostic markers based on biopsy specimens of
      colorectal cancer (CRC) are currently missing. We hypothesize that assessment of
      T-cell infiltration in biopsies of CRC may predict patient survival and TNM-stage
      before surgery. METHODS: Pre-operative biopsies and matched resection specimens
      from 130 CRC patients treated from 2002-2011 were included in this study. Whole
      tissue sections of biopsy material and primary tumors were immunostained for
      pancytokeratin and CD8 or CD45RO. Stromal (s) and intraepithelial (i) T-cell
      infiltrates were analyzed for prediction of patient survival as well as clinical
      and pathological TNM-stage of the primary tumor. RESULTS: CD8 T-cell infiltration
      in the preoperative biopsy was significantly associated with favorable overall
      survival (CD8i p = 0.0026; CD8s p = 0.0053) in patients with primary CRC
      independently of TNM-stage and postoperative therapy (HR [CD8i] = 0.55 (95% CI:
      0.36-0.82), p = 0.0038; HR [CD8s] = 0.72 (95% CI: 0.57-0.9), p = 0.0049). High
      numbers of CD8i in the biopsy predicted earlier pT-stage (p < 0.0001) as well as
      absence of nodal metastasis (p = 0.0015), tumor deposits (p = 0.0117), lymphatic
      (p = 0.008) and venous invasion (p = 0.0433) in the primary tumor. Infiltration
      by CD45ROs cells was independently associated with longer survival (HR = 0.76
      (95% CI: 0.61-0.96), p = 0.0231) and predicted absence of venous invasion (p =
      0.0025). CD8 counts were positively correlated between biopsies and the primary
      tumor (r = 0.42; p < 0.0001) and were reproducible between observers (ICC [CD8i]
      = 0.95, ICC [CD8s] = 0.75). For CD45RO, reproducibility was poor to moderate (ICC
      [CD45i] = 0.16, ICC [CD45s] = 0.49) and correlation with immune infiltration in
      the primary tumor was fair and non-significant (r[CD45s] = 0.16; p = 0.2864). For
      both markers, no significant relationship was observed with radiographic T-stage,
      N-stage or M-stage, indicating that assessment of T-cells in biopsy material can
      add additional information to clinical staging in the pre-operative setting.
      CONCLUSIONS: T-cell infiltration in pre-operative biopsy specimens of CRC is an
      independent favorable prognostic factor and strongly correlates with absence of
      nodal metastasis in the resection specimen. Quantification of CD8i is highly
      reproducible and allows superior prediction of clinicopathological features as
      compared to CD45RO. The assessment of CD8i infiltration in biopsies is
      recommended for prospective investigation.

PMID- 24679170
TI  - Maternal attention and preterm infant feeding.
AB  - PURPOSE: The purpose of this study was to explore the relationships among the
      mother's internal working model of feeding, attentional process, feeding
      behaviors, and responsiveness accounting for maternal psychological distress,
      which may contribute to preterm infants' feeding difficulties. DESIGN AND
      METHODS: In this descriptive study, 21 mother-preterm infant dyads were
      videotaped during feeding. RESULTS: Surprisingly, the internal working model of
      feeding was a significant negative predictor of maternal feeding behaviors and
      maternal attention. All other correlations were non-significant. CONCLUSIONS:
      Given the early timing of the data collection, it is possible that mothers had
      not developed a frame of reference of their infant as a person. Research to help
      further understand factors and timing affecting maternal feeding behaviors is
      needed.

PMID- 24679171
TI  - The uptake of arginine-rich cell-penetrating peptides: putting the puzzle
      together.
AB  - Over the past 20 years, cell-penetrating peptides (CPPs) have captured the
      attention of biomedical researchers, biophysicists, and (bio)organic chemists.
      These molecules efficiently enter cells and mediate entry of (macro)molecules
      that by themselves do not cross the plasma membrane. Since their discovery,
      models on the mechanism by which uptake occurs have seen major revisions.
      Starting from direct penetration across the plasma membrane, it later became
      apparent that for large molecular weight cargos in particular, endocytosis plays
      a role in uptake and furthermore that the route of uptake is a function of CPP,
      cell-type, cargo, and concentration. For the class of arginine-rich CPPs, this
      dependence on conditions has been elucidated in particular. As I will discuss
      here for this class of CPPs, a downside of this multitude of possibilities has
      been a lack of attention for commonalities in the observation of apparently
      distinct phenomena. At the same time, differences of apparently similar
      observations were not appreciated sufficiently. In addition, there has been
      insufficient acknowledgment of observations that are incompatible with the
      proposed models. Nevertheless, a considerable amount of data can be assembled
      into a quite coherent picture and the data that is left creates the basis for
      concrete future lines of research to resolve the questions that remain. Moreover,
      any uptake mechanism has its distinct structure-activity relationship for uptake
      giving room for the molecular design of molecules to preferentially direct uptake
      to either of them.

PMID- 24679173
TI  - Oxytocin and autism: a systematic review of randomized controlled trials.
AB  - OBJECTIVE: Little is known about the effectiveness of pharmacological
      interventions on autism spectrum disorder (ASD). This is a systematic review of
      the randomized controlled trials (RCTs) of oxytocin interventions in autism, made
      from January 1990 to September 2013. METHOD: A search of computerized databases
      was supplemented by manual search in the bibliographies of key publications. The
      methodological quality of the studies included in the review was evaluated
      independently by two researchers, according to a set of formal criteria.
      Discrepancies in scoring were resolved through discussion. RESULTS: The review
      yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with
      Fragile X syndrome. The main categories of target symptoms tested in the studies
      were repetitive behaviors, eye gaze, and emotion recognition. The studies had a
      medium to high risk of bias. Most studies had small samples (median=15). All the
      studies but one reported statistically significant between-group differences on
      at least one outcome variable. Most findings were characterized by medium effect
      size. Only one study had evidence that the improvement in emotion recognition was
      maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin
      was well tolerated and side effects, when present, were generally rated as mild;
      however, restlessness, increased irritability, and increased energy occurred more
      often under oxytocin. CONCLUSIONS: RCTs of oxytocin interventions in autism
      yielded potentially promising findings in measures of emotion recognition and eye
      gaze, which are impaired early in the course of the ASD condition and might
      disrupt social skills learning in developing children. There is a need for
      larger, more methodologically rigorous RCTs in this area. Future studies should
      be better powered to estimate outcomes with medium to low effect size, and should
      try to enroll female participants, who were rarely considered in previous
      studies. Risk of bias should be minimized. Human long-term administration studies
      are necessary before clinical recommendations can be made.

PMID- 24679174
TI  - Child and adolescent psychiatrists' attitudes and practices prescribing second
      generation antipsychotics.
AB  - OBJECTIVE: The purpose of this study was to examine psychiatrists' attitudes and
      practices in prescribing second-generation antipsychotics (SGA) to children and
      adolescents (referred to here as "children") and identify factors associated with
      off-label SGA use. METHODS: A survey was mailed to a national, randomly selected
      sample of 1600 child and adolescent psychiatrists identified by the American
      Medical Association. Multivariable logistic regression was used to identify
      factors, including psychiatrists' characteristics, practice characteristics, and
      psychiatrists' attitudes, that are associated with off-label SGA use (i.e., SGAs
      used in children with attention-deficit/hyperactivity disorder (ADHD),
      oppositional defiant disorder, conduct disorder, or nonbipolar mood disorders).
      RESULTS: The final sample included 340 psychiatrists. Overall, respondents
      reported higher use and appropriateness of SGAs for United States Food and Drug
      Administration (FDA)-approved disorders, symptoms of aggression, and older child
      age. More than one third (36%) of respondents reported some off-label SGA use.
      Significant predictors of off-label use were: Practicing at inpatient/residential
      facilities (odds ratio [OR]=4.2, p=0.001); white/non-Hispanic race/ethnicity
      (OR=0.3, p<0.0001), agreeing that SGAs should be used for ADHD with aggression
      (OR=7.1, p<0.0001); and agreeing that SGAs should be used for severe delinquent
      behaviors (OR=1.9, p=0.03). CONCLUSIONS: Psychiatrists' attitudes about
      prescribing SGAs to children exhibiting aggressive symptoms were associated with
      off-label SGA use. Research is needed to understand the construct of aggression,
      potential interaction effects of aggression with diagnostic criteria, and their
      impact on SGA use.

PMID- 24679175
TI  - Electroconvulsive therapy in an adolescent with severe major depression and
      anorexia nervosa.

PMID- 24679176
TI  - Lack of detectable serum levels following topical fluoxetine administration in a
      child.

PMID- 24679178
TI  - The cycle of classification: DSM-I through DSM-5.
AB  - The Diagnostic and Statistical Manual of Mental Disorders (DSM) was created in
      1952 by the American Psychiatric Association so that mental health professionals
      in the United States would have a common language to use when diagnosing
      individuals with mental disorders. Since the initial publication of the DSM,
      there have been five subsequent editions of this manual published (including the
      DSM-III-R). This review discusses the structural changes in the six editions and
      the research that influenced those changes. Research is classified into three
      domains: (a) issues related to the DSMs as measurement systems, (b) studies of
      clinicians and how clinicians form diagnoses, and (c) taxonomic issues involving
      the philosophy of science and metatheoretical ideas about how classification
      systems function. The review ends with recommendations about future efforts to
      revise the DSMs. 

PMID- 24679179
TI  - Development of clinical practice guidelines.
AB  - Clinical practice guidelines (CPGs) are intended to improve mental, behavioral,
      and physical health by promoting clinical practices that are based on the best
      available evidence. The American Psychological Association (APA) is committed to
      generating patient-focused CPGs that are scientifically sound, clinically useful,
      and informative for psychologists, other health professionals, training programs,
      policy makers, and the public. The Institute of Medicine (IOM) 2011 standards for
      generating CPGs represent current best practices in the field. These standards
      involve multidisciplinary guideline development panels charged with generating
      recommendations based on comprehensive systematic reviews of the evidence. The
      IOM standards will guide the APA as it generates CPGs that can be used to inform
      the general public and the practice community regarding the benefits and harms of
      various treatment options. CPG recommendations are advisory rather than
      compulsory. When used appropriately, high-quality guidelines can facilitate
      shared decision making and identify gaps in knowledge. 

PMID- 24679181
TI  - Elevated platelet count is a strong predictor of poor prognosis in stage I non
      small cell lung cancer patients.
AB  - Stage I non-small cell lung cancer (NSCLC) show a highly variable biological
      behavior which cannot be accurately predicted by the current available prognostic
      markers. Platelet plays a significant role in cancer cell growth, progression and
      metastasis. This study aimed to investigate whether preoperative platelet count
      correlate with clinical prognosis in localized NSCLC. A retrospective clinical
      analysis was designed for a total of 234 stage I NSCLC patients in our hospital
      between October 2006 and December 2009. Pre-operative platelet count was
      measured. The association of platelet count with clinical pathological factors
      and patient outcome was evaluated. A significant correlation was detected between
      platelet count and tumor cell differentiation and T stage. Patients with elevated
      platelet count had an elevated risk of disease progression and death compared to
      patients with normal platelet count. The hazard ratio was 5.314 (95% confidence
      interval [CI] 2.750-10.269) for disease progression and 3.139 (95% CI 1.227
      8.034) for death. The trend linking increasing platelet count with risk was also
      statistically significant for both the outcomes (p < 0.05). These finding
      demonstrate that preoperative platelet count is a useful predictor of high risk
      progression and poor prognosis in stage I NSCLC patients.

PMID- 24679182
TI  - Radioprotective effects of Nigella sativa oil against oxidative stress in liver
      tissue of rats exposed to total head irradiation.
AB  - OBJECTIVE: Many cancer patients treated with radiotherapy suffer severe side
      effects during and after their treatment. The aim of this study was to
      investigate the effects of irradiation and the addition of Nigella sativa oil
      (NSO) on the oxidant/antioxidant system in the liver tissue of irradiated rats.
      METHODS: A total of 24 Sprague-Dawley rats were randomly distributed into three
      groups of equal numbers. The control group received neither NSO nor irradiation
      but received 1-ml saline orally. The irradiation group (IR) received total head 5
      gray (Gy) of gamma irradiation as a single dose, plus 1-ml saline orally. The IR
      plus NSO group received both total head 5 Gy of gamma irradiation as a single
      dose and 1 g/kg/day NSO orally through an orogastric tube starting one hour
      before irradiation and continuing for 10 days. RESULTS: While liver tissue total
      oxidant status (TOS), lipid hydroperoxide (LOOH) level, and oxidative stress
      index (OSI) were significantly increased in the IR group compared to the control
      group, total antioxidant status (TAS), sulfhydryl (-SH) levels, and PON activity
      were significantly decreased. Cp activity in the IR plus NSO and IR groups was
      higher than in the control group. ARYL activity in the IR plus NSO supplemented
      group was higher than that in other groups. CONCLUSIONS: NSO reduces oxidative
      stress markers and has antioxidant effects, which also augments the antioxidant
      capacity in the liver tissue of rats.

PMID- 24679183
TI  - Even mildly elevated TSH is associated with an atherogenic lipid profile in
      postmenopausal women with subclinical hypothyroidism.
AB  - Postmenopausal women, a population with increased risk of atherosclerosis, also
      have an appreciable risk of subclinical hypothyroidism (SCH). The current study
      sought an association between serum thyrotropin (TSH), the biomarker of SCH and
      atherosclerosis lipid profile changes. A total of 45 postmenopausal women with
      SCH and 27 healthy women matched by age and body mass index were enrolled in this
      observational study. Serum lipid profiles and thyroid function were assessed.
      Compared with healthy controls, the serum levels of TC, TG, LDL-c and oxidized
      LDL (oxLDL) in SCH were increased by ~22.8%, 29.6%, 30.5% and 23.2%,
      respectively. TSH was positively correlated with TC, LDL-c and oxLDL in all of
      the study subjects after adjusting for age and BMI. In particular, the positive
      correlation remained significant after adjusting for serum FT3 and FT4. When
      further stratified by TSH levels, both the subgroup of mildly elevated TSH (4.78
      9.99 mU/L) and overtly elevated TSH (>10.00 mU/L) exhibited significantly higher
      serum levels of TC, TG, LDL-c and oxLDL compared to the normal TSH subgroup. Path
      analysis revealed that the total effects of TSH on TC (total effectsTC,TSH =
      0.4323) included a significant direct effect (direct effectTC,TSH = 0.4932) and
      an indirect effect via an intermediary variable (FT3, FT4). Furthermore, TC
      exhibited a direct effect on LDL-c, as did LDL-c on oxLDL. In conclusion, even
      with a mild elevation of serum TSH, SCH is associated with atherogenic lipid
      profiles in postmenopausal women independent of thyroid hormones.

PMID- 24679185
TI  - Spinal cord injury following operative shoulder intervention: A case report.
AB  - CONTEXT: Cervical myelopathy is a spinal cord dysfunction that results from
      extrinsic compression of the spinal cord, its blood supply, or both. It is the
      most common cause of spinal cord dysfunction in patients greater than 55 years of
      age. FINDINGS: A 57-year-old male with right shoulder septic arthritis underwent
      surgical debridement of his right shoulder and sustained a spinal cord injury
      intraoperatively. The most likely etiology is damage to the cervical spinal cord
      during difficult intubation requiring multiple attempts in this patient with
      underlying asymptomatic severe cervical stenosis. CONCLUSION: Although it is not
      feasible to perform imaging studies on all patients undergoing intubation for
      surgery, this patient's outcome would suggest consideration of inclusion of
      additional pre-surgical screening examination techniques, such as testing for a
      positive Hoffman's reflex, is appropriate to detect asymptomatic patients who may
      have underlying cervical stenosis.

PMID- 24679184
TI  - Single nucleotide polymorphism rs6716901 in SLC25A12 gene is associated with
      Asperger syndrome.
AB  - BACKGROUND: Autism Spectrum Conditions (ASC) are a group of developmental
      conditions which affect communication, social interactions and behaviour.
      Mitochondrial oxidative dysfunction has been suggested as a mechanism of autism
      based on the results of multiple genetic association and expression studies.
      SLC25A12 is a gene encoding a calcium-binding carrier protein that localizes to
      the mitochondria and is involved in the exchange of aspartate for glutamate in
      the inner membrane of the mitochondria regulating the cytosolic redox state.
      rs2056202 SNP in this gene has previously been associated with ASC. SNPs
      rs6716901 and rs3765166 analysed in this study have not been previously explored
      in association with AS. METHODS: We genotyped three SNPs (rs2056202, rs3765166,
      and rs6716901) in SLC25A12 in n?=?117 individuals with Asperger syndrome (AS) and
      n?=?426 controls, all of Caucasian ancestry. RESULTS: rs6716901 showed
      significant association with AS (P?=?0.008) after correcting for multiple
      testing. We did not replicate the previously identified association between
      rs2056202 and AS in our sample. Similarly, rs3765166 (P?=?0.11) showed no
      significant association with AS. CONCLUSION: The present study, in combination
      with previous studies, provides evidence for SLC25A12 as involved in the etiology
      of AS. Further cellular and molecular studies are required to elucidate the role
      of this gene in ASC.

PMID- 24679180
TI  - The behavioral economics of substance use disorders: reinforcement pathologies
      and their repair.
AB  - The field of behavioral economics has made important inroads into the
      understanding of substance use disorders through the concept of reinforcer
      pathology. Reinforcer pathology refers to the joint effects of (a) the
      persistently high valuation of a reinforcer, broadly defined to include tangible
      commodities and experiences, and/or (b) the excessive preference for the
      immediate acquisition or consumption of a commodity despite long-term negative
      outcomes. From this perspective, reinforcer pathology results from the recursive
      interactions of endogenous person-level variables and exogenous environment-level
      factors. The current review describes the basic principles of behavioral
      economics that are central to reinforcer pathology, the processes that engender
      reinforcer pathology, and the approaches and procedures that can repair
      reinforcement pathologies. The overall goal of this review is to present a new
      understanding of substance use disorders as viewed by recent advances in
      behavioral economics. 

PMID- 24679186
TI  - A combined theoretical and Cambridge Structural Database study of pi-hole
      pnicogen bonding complexes between electron rich molecules and both nitro
      compounds and inorganic bromides (YO2Br, Y = N, P, and As).
AB  - Quantum calculations at the DFT-D3/def2-TZVPD level of theory have been used to
      examine complexes between O2YBr (Y?N, P, and As) molecules and several Lewis
      bases, that is, NH3, H2O, and HF. The interactions of the lone pair of the
      ammonia, water, and hydrogen fluoride with the sigma-hole and pi-hole of O2YBr
      molecules have been considered. In general, the complexes where the Lewis base
      lone pair interacts with the pi-hole are more favorable than those with sigma
      hole. The nature of the interactions has been characterized with the Bader theory
      of atoms in molecules (AIM). We have also studied the ability of
      trifluoronitromethane and nitromethane to interact with anions using their pi
      hole along with an analysis the Cambridge Structural Database. We have found a
      large number of hits that provide strong experimental support for ability of the
      nitryl (-NO2) group to interact with anions and Lewis bases. In some X-ray
      structures, the pi-hole interaction is crucial in the crystal packing and has a
      strong influence in the solid state architecture of the complexes. Finally, due
      to the relevance in atmospheric chemistry, we have studied noncovalent sigma/pi
      hole complexes of nitryl bromide with ozone. 

PMID- 24679187
TI  - Empirical treatment for TB in HIV: lessons from a cohort study of people living
      with HIV treated in Recife, Brazil.
AB  - BACKGROUND: Tuberculosis (TB) is the leading cause of death related to HIV
      worldwide. This study analyzes the survival of People Living with HIV (PLHIV)
      reporting cough without bacteriological confirmation of TB and identify factors
      associated with death. METHODS: Prospective cohort with a consecutive sample of
      PLHIV, aged >= 18 years. Patient inclusion criteria were complaint of current
      cough of any duration at the time of the first study interview or during their
      subsequent routine visits to health services and for whom AFB sputum smear was
      either negative or not performed during the whole follow-up period. Kaplan-Meier
      method was used to calculate the probability of survival. We estimated the Hazard
      Ratio (HR) in bivariate and multivariate Cox regression analyses. RESULTS:
      Mortality was 4.6 per 100 py; 73% were receiving HAART at recruitment. Average
      time from the first recorded date of cough until empirical treatment for
      tuberculosis was six months. Mortality was higher when the CD4 count was low (HR
      = 5.3; CI 95%: 3.2-9.0; p = 0.000), in those with anemia (HR = 3.0; CI 95%: 1.6
      5.6; p = 0.001) and with abnormal chest X-rays (HR = 2.4; CI 95%: 1.4-4.0; p =
      0.001). Mortality was higher in those receiving empirical TB treatment (HR = 2.4;
      CI 95%: 1.4-4.0; p = 0.002), but only in those with normal X-rays, no history of
      tuberculosis and no bacteriology requests. Empirical treatment for TB was more
      frequent in PLHIV with low CD4 counts, anemia, history of opportunistic
      infections, weight loss, previous tuberculosis, negative bacteriology test (as
      opposed to not having a test) and abnormal chest X-ray. CONCLUSIONS: Higher
      mortality in PLHIV reporting a current cough without bacteriological confirmation
      of tuberculosis was identified for those with a CD4 cell count <200, abnormal
      chest X-ray, anemia and empirical treatment for tuberculosis. Mortality was not
      significantly higher in those empirically treated for TB, who had three
      characteristics suggestive of the disease (abnormal chest X-ray, history of TB
      treatment, AFB sputum smear or M.tb culture testing). Routine cohorts are not an
      adequate setting to evaluate the impact of empirical treatment for TB on the
      mortality of PLHIV.

PMID- 24679188
TI  - An investigation of a hypothermic to ischemic ratio in patients following out-of
      hospital cardiac arrest presenting with a shockable rhythm.
AB  - Targeted temperature management (TTM) improves outcome after out-of-hospital
      cardiac arrest (OHCA). We hypothesized that there may be a significant
      relationship between the dose of hypothermia, the time to return of spontaneous
      circulation (ROSC), and survival to discharge. Retrospective pilot investigation
      on 99 consecutive OHCA patients with initial shockable rhythm, surviving to
      admission, and undergoing TTM between 2008 and 2011. Dose of hypothermia was
      defined as the sum of the induction interval (time to target temperature [from
      ROSC to 33 degrees C]); the controlled hypothermia interval (from reaching 33
      degrees C until rewarming); and the rewarming interval (from 33 degrees C to 37
      degrees C). Time to ROSC was measured from pulselessness or 911 call time to
      ROSC. The ratio between the two was termed the hypothermic to ischemic ratio.
      Purposeful variable selection for logistic regression modeling was used to assess
      the influence of the hypothermic/ischemic ratio on survival. Odds ratios (OR)
      were used to examine the effects of predictor variables on survival. Of 99
      patients, eight were excluded for deviation from protocol, death during protocol,
      or missing data. From the univariate models, survivors were more likely to be
      younger, have a shorter time to ROSC, and have a larger hypothermic/ischemic
      ratio. Survivors also had a nonsignificant trend toward a longer time to target
      temperature. In multivariable modeling, the hypothermic/ischemic ratio was the
      most significant predictor for survival (OR 2.161 [95% confidence interval 1.371,
      3.404]). In this pilot study, the hypothermic to ischemic ratio was significantly
      associated with survival to discharge for patients with an initial shockable
      rhythm. Further investigation of the relationship between the dose of hypothermia
      and time to ROSC for postresuscitation TTM is needed. 

PMID- 24679189
TI  - Heterogeneity in patient diagnostic pathways: an example from contrast-enhanced
      ultrasound diagnostic scans for focal liver lesions.
AB  - BACKGROUND: The UK's National Institute for Health and Care Excellence (NICE) has
      recommended contrast-enhanced ultrasound (CEUS) for the characterisation of focal
      liver lesions where the results of standard unenhanced ultrasound are
      inconclusive. A further recommendation is for CEUS to replace other imaging
      modalities. However, little is currently known about the diagnostic pathways in
      the National Health Service (NHS) followed by patients with potential liver
      lesions. The aim of this study was to identify the diagnostic pathways for a
      number of representative hospital trusts and record the clinicians' views on
      patient experiences of these processes through a series of semi-structured
      interviews with UK clinicians (radiologists and sonographers) (N = 7). This study
      was undertaken in the broader context of a larger research project where the
      overarching research question is focused on patient preferences for CEUS and
      other imaging modalities, and how these impact on patient quality of life (QOL).
      RESULTS: The results from the semi-structured interviews with UK clinicians
      revealed that there is a great deal of heterogeneity in diagnostic pathways
      followed by patients with potential liver lesions which differ both within and
      between hospitals. In terms of the patient experience, the clinicians believed
      that a combination of the more patient-friendly ultrasound process, and the fact
      that scan results are given to patients in 80-90% of cases on the day, as well as
      the problems inherent to other scan modalities (claustrophobia, anxiety) would
      lead to patients preferring ultrasound compared with other imaging modalities (CT
      or MR). However, current clinical practice means that patient choice is virtually
      non-existent. CONCLUSIONS: The significant variation in diagnostic pathways
      across the NHS will require further standardisation through local agreements if
      contrast-enhanced ultrasound is to replace other imaging modalities in
      characterising focal liver lesions in line with NICE Diagnostics Guidance. The
      gradual development of patient choice of modalities may necessitate a change of
      practice in radiology processes.

PMID- 24679190
TI  - Dual-incision approach for repair of peroneal tendon dislocation associated with
      fractures of the calcaneus.
AB  - Dislocation of the peroneal tendons associated with calcaneus fractures should be
      repaired during fracture fixation to prevent complications. The only documented
      approach for repair is by proximal extension of the vertical limb of the lateral
      extensile approach to the calcaneus. However, enlarging the inherently fragile
      calcaneus flap places it at further risk of damage. Using a separate anterior
      incision to repair the dislocation, thus avoiding problems caused by excessive
      flap elevation, seemed intuitive. This approach proved technically effective and
      reliable in producing favorable outcomes in a series of 14 patients.

PMID- 24679191
TI  - Limb-length discrepancy after total hip arthroplasty: novel treatment and
      proposed algorithm for care.
AB  - Limb-length discrepancy after total hip arthroplasty (THA) leads to patient
      dissatisfaction and can be a cause of orthopedic surgery malpractice cases.
      Nonsurgical and surgical techniques exist to correct limb-length discrepancies.
      Two limb-lengthening methods were used to correct greater than 2-cm limb-length
      discrepancies after THA: lengthening over a femoral nail with an external fixator
      and lengthening with an intramedullary kinetic skeletal distractor. These
      techniques achieved equal length in less than 4 weeks, with both resulting in a
      healed distraction gap within 4 months. No patient had loss of proximal or distal
      joint motion, and mean Harris Hip Score was 90 points at final follow-up. No
      surgical complications were reported with the intramedullary skeletal kinetic
      distractor. Limb lengthening using an intramedullary skeletal kinetic distractor
      is a viable treatment option resulting in reliable lengthening, healing of the
      distraction gap, and progression to full weight bearing.

PMID- 24679192
TI  - Ensuring correct placement of proximal fixation in reconstruction intramedullary
      nailing for subtrochanteric femur fractures.
AB  - Subtrochanteric femur fractures present a challenge to orthopedic surgeons.
      Anatomic reduction and stabilization can be technically difficult. A variety of
      intramedullary and extramedullary devices have been used to stabilize these
      fractures. The authors describe a novel technique for easier proximal interlock
      fixation for reconstruction intramedullary nailing to ensure proper placement
      into the nail. This will likely save time in a patient population that may be
      either frail and elderly or young with high-energy polytrauma, and it may reduce
      radiation exposure for both patients and surgeons.

PMID- 24679193
TI  - Giant cell tumor of bone.
AB  - EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be
      able to: 1. Identify at-risk populations for giant cell tumor of bone. 2.
      Recognize the biology that drives giant cell tumor of bone. 3. Describe modern
      surgical and adjuvant techniques to effectively treat giant cell tumor of bone.
      4. Recognize the complications associated with radiation therapy, poor resection,
      and adjuvant treatments. Giant cell tumor of bone (GCT) is a benign, locally
      aggressive bone tumor. Giant cell tumor of bone primarily affects the young adult
      patient population. The natural history of GCT is progressive bone destruction
      leading to joint deformity and disability. Surgery is the primary mode of
      treatment, but GCT has a tendency to recur locally despite a range of adjuvant
      surgical options. Pulmonary metastasis has been described. However, systemic
      spread of GCT rarely becomes progressive, leading to death. This review presents
      the clinicopathologic features of GCT and a historical perspective that
      highlights the current rationale and controversies regarding the treatment of
      GCT.

PMID- 24679194
TI  - Return to sport after ACL reconstruction.
AB  - Objective guidelines permitting safe return to sport following anterior cruciate
      ligament (ACL) reconstruction are infrequently used. The purpose of this study
      was to determine the published return to sport guidelines following ACL
      reconstruction in Level I randomized controlled trials. A systematic review was
      performed using Preferred Reporting Items for Systematic reviews and Meta
      Analyses (PRISMA) guidelines. Level I randomized controlled trials were included
      if they reported a minimum 2-year follow-up after ACL reconstruction and return
      to sport criteria. Outcomes analyzed were the timing of initiation of return to
      sport, follow-up duration, and use of quantitative/qualitative criteria to
      determine return to sport. Forty-nine studies were included (N=4178; 68% male;
      mean patient age, 27.5+/-3.2 years; mean follow-up, 3.0+/-1.9 years; mean time
      from injury to reconstruction, 379+/-321 days). Ninety-six percent of
      reconstructions used autograft and 87% were single-bundle reconstructions.
      Lysholm score, single-leg hop, isokinetic strength, and KT-1000 or KT-2000
      arthrometer (MEDmetric, San Diego, California) testing were performed in 67%,
      31%, 31%, and 82% of studies, respectively. Only 5 studies reported whether
      patients were able to successfully return to sport. Ninety percent and 65% of
      studies failed to use objective criteria or any criteria, respectively, to permit
      return to sport. Description of permission/allowance to return to sport was
      highly variable and poor. Twenty-four percent of studies failed to report when
      patients were allowed return to sport without restrictions. Overall, 39%, 45%,
      and 51% of studies permitted running at 3 months, return to cutting/pivoting
      sports at 6 months, and return to sport without restrictions at 6 months,
      respectively. Further research into validated return to sport guidelines is
      necessary to fill the existing void in contemporary literature and to guide
      clinical practice. 

PMID- 24679195
TI  - Value of knee MRI in the diagnosis and management of knee disorders.
AB  - The primary objectives of this study were to determine how frequently knee
      magnetic resonance imaging (MRI) changes (1) diagnosis, (2) diagnostic
      confidence, and (3) management. A secondary objective was to correlate these
      changes with specific patient/physician characteristics and develop a prediction
      model using these characteristics. Six orthopedic specialists prospectively
      completed surveys when ordering knee MRI (n=93). Pre-MRI surveys recorded
      history, symptoms, signs, diagnosis, diagnostic confidence, and planned
      management. Post-MRI surveys recorded diagnosis, confidence, and planned
      management. Changes in diagnosis, management, and diagnostic confidence were
      correlated with patient/physician characteristics using chi-square and logistic
      regression tests. A multiple variable model was created with the most significant
      variables from the univariate analysis, and a c-index was used for cross
      validation. Magnetic resonance imaging changed diagnosis in 29.3% and management
      in 25.3% of cases. Confidence in diagnoses after MRI increased, on average, by
      10.6%. Change in diagnosis was significantly correlated with lateral joint line
      pain (P=.012) and tenderness (P=.006). The 3 most significant predictors for
      change in management were ligament pathology (P=.017), medial-sided
      pain/tenderness (P=.051), and age (P=.133). A 3-variable model using these
      predictors was significantly better than chance alone at predicting management
      changes (c-index: model=0.766; cross-validation=0.661). Magnetic resonance
      imaging frequently changed diagnosis and management and improved diagnostic
      confidence in a large minority of patients with internal derangement of the knee,
      even after evaluation by subspecialized physicians. A statistical model using
      specific patient characteristics can be created to predict when MRI will change
      management. 

PMID- 24679196
TI  - Anterior decompression and fusion versus posterior laminoplasty for multilevel
      cervical compressive myelopathy.
AB  - The optimal surgical strategy for anterior or posterior approaches remains
      controversial for multilevel cervical compressive myelopathy caused by
      multisegment cervical spondylotic myelopathy (MCSM) or ossification of the
      posterior longitudinal ligament (OPLL). A systematic review and meta-analysis was
      conducted evaluating the clinical results of anterior decompression and fusion
      (ADF) compared with posterior laminoplasty for patients with multilevel cervical
      compressive myelopathy. PubMed, Embase, and the Cochrane Library were searched
      for randomized controlled trials and nonrandomized cohort studies conducted from
      1990 to May 2013 comparing ADF with posterior laminoplasty for the treatment of
      multilevel cervical compressive myelopathy due to MCSM or OPLL. The following
      outcome measures were extracted: Japanese Orthopedic Association (JOA) score,
      recovery rate, complication rate, reoperation rate, blood loss, and operative
      time. Subgroup analysis was conducted according to the mean number of surgical
      segments. Eleven studies were included in the review, all of which were
      prospective or retrospective cohort studies with relatively low quality indicated
      by GRADE Working Group assessment. A definitive conclusion could not be reached
      regarding which surgical approach is more effective for the treatment of
      multilevel cervical compressive myelopathy. Although ADF was associated with
      better postoperative neural function than posterior laminoplasty in the treatment
      of multilevel cervical compressive myelopathy due to MCSM or OPLL, there was no
      apparent difference in the neural function recovery rate between the 2
      approaches. Higher rates of surgery-related complication and reoperation should
      be taken into consideration when ADF is used for patients with multilevel
      cervical compressive myelopathy. The surgical trauma associated with corpectomy
      was significantly higher than that associated with posterior laminoplasty. 

PMID- 24679197
TI  - Osteoinductive activity of ErhBMP-2 after anterior cervical diskectomy and fusion
      with a beta-TCP interbody cage in a goat model.
AB  - Bone morphogenetic protein (BMP)-2 induces bone and cartilage tissue formation.
      Large amounts of BMP-2 are difficult to purify or to produce in vitro using
      eukaryotic cells. The goal of the present study was to assess the clinical use of
      Escherichia coli-derived recombinant human BMP-2 (ErhBMP-2) on bone fusion after
      cervical and lumbar spine surgery in a goat model, compared with the standard
      autogenous iliac bone grafting. Thirty-six goats were randomized to 3 groups: (A)
      autogenous iliac bone grafting, (B) cervical interbody fusion cage containing
      beta-tricalcium phosphate (beta-TCP), or (C) cervical interbody fusion cage
      containing beta-TCP+ErhBMP-2 (2.5 mg). Cervical bone repair was evaluated using
      radiographs and computed tomography scans at 0, 3, and 6 months. Histological
      analyses were performed on cervical samples. Two goats died from infection. The
      differences in intervertebral height among the groups were not significant 3
      months postoperatively but became significant after 6 months between groups A vs
      B and C (P=.04); there was no difference between groups B and C at 6 months.
      Adding ErhBMP-2 significantly increased cervical fusion at 6 months (P=.04).
      Histological examinations showed that beta-TCP+ErhBMP-2 increased new bone area,
      material degradation rate, and depth of tissue penetration and decreased residual
      material area, all in a time-dependent manner. Escherichia coli-derived rhBMP-2
      combined with an enhanced fusion cage containing beta-TCP induced bone formation
      in a goat model. Furthermore, its ability to promote bone fusion was similar to
      autogenous iliac bone grafting. 

PMID- 24679198
TI  - Disparities in internet use among orthopedic outpatients.
AB  - Internet access has lagged behind for patients with lower incomes and from
      certain ethnic groups. This study investigated the possible improvement of access
      to health-related information on the Internet for all patients in an urban
      outpatient setting, regardless of socioeconomic background. A 28-question survey
      was completed by 100 orthopedic outpatients evaluating associations between their
      age, ethnicity, income, or education level and their access to the Internet. The
      survey also examined how patients used the Internet to obtain information about
      their medical condition, their privacy concerns when conducting online research,
      and their use of mobile phones as a primary means of Internet access. The
      Internet was used by 57% of orthopedic outpatients in this urban setting.
      Internet access decreased with advancing age but increased with increasing income
      and education, findings consistent with similar studies. Despite the inability to
      identify an association between ethnicity and Internet access in this patient
      population, fewer Latinos (33%) than whites (67%) or African Americans (77%)
      sought information about their medical condition. Among patients who used a
      mobile phone as the primary method for online access, 74% were African American
      or Latino and 26% were white. This difference in mobile phone use for online
      access suggests that mobile phones have provided ethnic minorities with greater
      Internet access and thus may have narrowed the digital divide among the races. 

PMID- 24679199
TI  - First metatarsophalangeal joint arthrodesis for the treatment of tophaceous gouty
      arthritis.
AB  - In tophaceous gouty arthritis, surgeons face the choice between preservation of
      the involved joint and arthrodesis after tophi excision. Magnetic resonance
      imaging (MRI) can allow evaluation of the distribution of tophaceous deposits,
      which can be difficult to visualize on radiography. The goal of this study was to
      evaluate the characteristic MRI features of tophaceous lesions and to compare the
      clinical outcomes of arthrodesis after tophi excision with those of simple tophi
      excision. The authors reviewed 16 feet in 15 consecutive patients diagnosed with
      tophaceous gouty arthritis of the first metatarsophalangeal (MTP) joint who
      underwent surgery. Nine feet (group A) were treated with simple tophi excision,
      whereas the other 7 (group B) underwent first MTP joint arthrodesis after tophi
      excision. For clinical evaluation, the visual analog scale (VAS) for pain,
      American Orthopaedic Foot and Ankle Society (AOFAS) score, Tegner activity scale,
      and patient satisfaction assessments were used. Magnetic resonance imaging was
      performed to evaluate the characteristics of tophaceous deposits in the first MTP
      joint. Mean VAS and AOFAS scores and patient satisfaction significantly differed
      between the 2 groups at final follow-up (P=.007, .005, and .002, respectively).
      In group A, progression of arthritis of the first MTP joint was observed in 6 of
      9 cases at final follow-up. The tophaceous lesions of these 6 cases were found to
      be located intra-articularly on MRI. Arthrodesis after tophi excision should be
      considered for treating tophaceous gouty arthritis of the first MTP joint when
      tophi are located intra-articularly and loss of cartilage involved is greater
      than 50% of the entire joint. 

PMID- 24679200
TI  - Cost-effectiveness of MRI to assess for posttraumatic ligamentous cervical spine
      injury.
AB  - Magnetic resonance imaging (MRI) has been shown to be sensitive in identifying
      ligamentous injury to the cervical spine. The major drawbacks to its routine use
      are cost and availability. The purpose of this study was to compare the cost of
      using MRI to rule out ligamentous injury of the cervical spine with the cost of
      immobilization in a cervical collar and outpatient follow-up. Neurologically
      intact and nonobtunded patients with neck pain and normal findings on radiographs
      evaluated for ligamentous injury of the cervical spine were studied. Patients
      were either evaluated with MRI or immobilized in a cervical collar and followed
      up for repeat clinical and radiographic evaluation as outpatients. The authors
      gathered year 2011 fees from their institution and 2011 Medicare reimbursement
      data and compared the costs of MRI with the costs of cervical collar and
      outpatient follow-up. In addition, the median income of the local community was
      used to estimate opportunity costs associated with cervical collar
      immobilization. After 7 days of lost wages at the median local income, MRI became
      a less costly option when comparing hospital fees. Alternatively, when
      considering Medicare reimbursement, MRI became less costly after only 2 days of
      lost wages at the median local income. On the basis of these findings, MRI of the
      cervical spine is less costly than other current management strategies when
      opportunity costs are considered. 

PMID- 24679201
TI  - Efficacy of delayed decompression of lumbar disk herniation causing cauda equina
      syndrome.
AB  - Cauda equina syndrome (CES) is a rare but serious neurosurgical emergency that
      can have devastating long-lasting neurologic consequences. Compression of the
      cauda equina can result in paralysis of bowel and bladder function. Such
      compression has been considered the only absolute indication for surgery in cases
      of lumbar disk disease. Therefore, it is extremely important that physicians be
      aware of the condition so that a surgeon is consulted before neurological damage
      becomes permanent. This article reports the results of delayed surgical
      decompression in cases of lumbar disk herniation with CES. The study group
      comprised 14 patients (11 men and 3 women) with a mean age of 48 years (range, 36
      57 years). Clinical presentation was chronic low back pain, sciatica, and
      impaired sphincter function. All patients had a fenestration at the affected
      level and site, and the disk fragments were excised and the disk space cleared.
      The surgeries were performed 1 to 3 months after onset of sphinctric disturbance.
      Postoperatively, all patients were relieved of back and/or leg pain and showed
      sensory improvement. Twelve patients regained full control of urination and
      defecation. Lower extremity strength improved in 9 patients. The classical
      presentation of CES is not obvious. Even if surgery is performed late due to
      delayed presentation, significant improvement in neurologic and bladder function
      can still be expected. 

PMID- 24679202
TI  - CT characterizing the anatomy of uninjured ankle syndesmosis.
AB  - Although it is expert opinion that transsyndesmotic screws are placed obliquely
      30 degrees  from posterolateral to anteromedial in the transverse plane, this has
      not been formally studied, and there is inconsistency regarding the congruency of
      the distal tibiofibular joint. Thirty-eight computed tomography (CT) scans of the
      lower extremity were used to examine the rotational profile of the axis of the
      syndesmotic joint in relation to the femoral transepicondylar axis and to
      describe the congruency of this joint. The axis of the distal tibiofibular joint
      was 32 degrees +/-6 degrees  externally rotated in relation to the
      transepicondylar axis. The average anterior, central, and posterior widths of the
      syndesmotic joint space 10 mm superior to the joint line were statistically
      significantly different: 1.7+/-0.9 mm, 1.7+/-0.6 mm, and 2.3+/-1.1 mm,
      respectively (P=.004). This study demonstrates that the axis of the uninjured
      distal tibiofibular joint is approximately 30 degrees  externally rotated in
      relation to the transepicondylar axis. Therefore, reduction clamps and screws
      should be placed at this angle to avoid malreduction of the syndesmosis. The
      posterior joint space width is significantly wider than the anterior and central
      joint spaces. This study's results provide a description of the anatomy of the
      uninjured distal tibiofibular joint to guide reduction maneuvers and establish a
      baseline for evaluation of postreduction CT scans. 

PMID- 24679203
TI  - Clinical comparison of 2 implantation systems for single-level cervical disk
      replacement.
AB  - The safety and effectiveness of 2 implantation systems for single-segment
      cervical disk replacement-the Bryan Cervical Disc System (Medtronic Inc,
      Minneapolis, Minnesota) and the ACCEL system (Medtronic Inc)-have not been
      clinically compared. A prospective, nonrandomized controlled study in consecutive
      patients with a minimum 2-year follow-up was performed. Fifty patients with
      single-level cervical disk degeneration who responded poorly to conservative
      treatment and underwent Bryan Cervical Disc replacement were involved. Fifty
      patients were included (24 in group A [Bryan Cervical Disc System] and 26 in
      group B [ACCEL system]).The patients' visual analog scale scores, Neck Disability
      Index (NDI) scores, Short Form 36 (SF-36) scores, Odom scores, operative time,
      blood loss, and complications were compared. Patients' baseline statuses were
      similar (P>.05). Visual analog scale for neck and arm pain, NDI, and SF-36 were
      significantly improved postoperatively (P<.05) in both groups, and no clinical
      differences were found between the groups (P>.05). All Odom scores were better
      than good. Mean operative time and average blood loss in group A (173+/-42.5
      minutes and 250+/-159.8 mL, respectively), were both significantly higher than
      the values in group B (137.5+/-19.3 minutes and 138.1+/-86.7 mL, respectively)
      (P<.05). Complications included intraoperative bleeding, temporary throat
      discomfort, and slight migration of the prosthesis; there was no significant
      difference in the total complication rates between the 2 groups (P>.05). The 2
      implantation systems displayed equal clinical effectiveness and safety, but the
      ACCEL system appears to have the advantages of shorter operative time and less
      blood loss. 

PMID- 24679204
TI  - Biomechanical comparison of volar locked plate constructs using smooth and
      threaded locking pegs.
AB  - The goal of this study was to determine whether there is any biomechanical
      difference in terms of construct strength with axial loading between volar fixed
      angle locking plates with threaded locking vs smooth locking pegs. The control
      group comprised 7 cadaveric specimens with threaded locking pegs, and the test
      group comprised 7 cadaveric specimens from the same donor with smooth locking
      pegs. The DVR plate (Biomet, Warsaw, Indiana) was applied to the volar surface. A
      15-mm dorsal wedge osteotomy was created near the level of Lister's tubercle. The
      radii were potted in polymethylmethacrylate for biomechanical testing. The
      loading protocol consisted of 3 parts: ramp loading, cyclic loading, and failure
      loading. The outcome measures of stiffness and failure were used to test the
      plates fixed with threaded and smooth locking pegs. When comparing each cycle,
      the difference in mean stiffness between threaded and smooth locking pegs was as
      follows: 122 N/mm, -9.09 N/mm, -14.7 N/mm, 49.4 N/mm, 57.4 N/mm, 71.9 N/mm, 52.3
      N/mm, 35.8 N/mm. The difference in mean failure load between the threaded and
      smooth locking pegs was -11.3 N. There was no difference in stiffness throughout
      all cycles. Failure analysis showed no significant difference between the smooth
      (962 N) and threaded (951 N) locking pegs. The difference in stiffness between
      the 2 constructs (smooth minus threaded locking pegs) in ramp loading ranged from
      -122 to 15 N/mm. The results of this study showed no significant differences in
      stiffness and failure load between constructs consisting of threaded locking pegs
      or smooth locking pegs in the distal rows of the DVR distal radius volar locking
      plate. Based on the results of this study, there may be no benefit to using
      threaded locking pegs vs smooth locking pegs when treating distal radius
      fractures with a volar locking plate. 

PMID- 24679205
TI  - Posterior sternoclavicular joint injuries in skeletally immature patients.
AB  - The management of sternoclavicular injuries in skeletally immature patients has
      not been well described. The purpose of this study was to describe the authors'
      experience treating this rare and potentially life-threatening injury. All
      skeletally immature patients who underwent treatment for a medial clavicular
      physeal fracture or sternoclavicular dislocation between 2003 and 2011 were
      identified using ICD-9 diagnostic codes. Sternoclavicular injuries with posterior
      displacement were isolated from this cohort for a thorough chart review. Patients
      were contacted to complete brief phone surveys and shoulder-specific outcome
      instruments. A total of 12 boys (mean age, 14.8+/-2.74 years), followed for an
      average of 10.3 months (range, 0-54 months), were identified. The incidence of
      significant associated symptoms was 8.3% (1 of 12). Eight patients were initially
      treated with closed reduction, 2 (25%) successfully and 6 (75%) requiring
      subsequent open reduction. Four of the 12 patients underwent an immediate open
      reduction. Braided composite sutures were used to treat all injuries that
      underwent open reduction (10 of 12). Complete data were obtained from 6 patients,
      all of whose injuries had been treated with open reduction. All 6 had returned to
      their full activity level, and all self-reported perfect Quick Disabilities of
      the Arm, Shoulder and Hand (QuickDASH) and Simple Shoulder Test scores (0 and 12,
      respectively). Among skeletally immature patients, medial clavicular physeal
      fractures and sternoclavicular dislocations can be effectively managed with
      closed or open reduction. When closed reduction is unsuccessful or is
      contraindicated, open reduction with braided composite sutures is associated with
      excellent results. 

PMID- 24679206
TI  - Seasonality of infection rates after total joint arthroplasty.
AB  - The correlation between season (fall, winter, spring, and summer) and infection
      rate in surgical patients is well defined in many specialties. To the authors'
      knowledge, there are no data in the literature on this phenomenon in patients
      undergoing total joint arthroplasty. They hypothesized that there would be an
      increased infection rate in the summer months in patients undergoing elective
      total joint arthroplasty. They retrospectively reviewed consecutive patients
      undergoing elective total hip or knee arthroplasty at a single institution during
      1 year by a single surgeon. Wound infections were defined as any patient
      requiring oral antibiotics for cellulitis, readmission for intravenous
      antibiotics, a return to the operating room for irrigation and debridement, or
      excisional arthroplasty and placement of a cement spacer within 90 days of the
      initial procedure. Seventeen of 750 patients developed an infection, for an
      overall incidence of 2.2%. There was a statistically significant difference in
      infection rate according to season: 3 (1.5%) infections occurred in winter, 1
      (0.5%) in spring, 9 (4.7%) in summer, and 4 (2.4%) in fall. The incidence was
      highest during July (4.5%), August (5.4%), and September (4.3%). There was a
      statistically significant difference in infection rate between summer/fall (3.6%)
      vs winter/spring (1.0%). There is an increase in the incidence of infection
      during summer months for patients undergoing total joint arthroplasty. The
      authors recommend increased surveillance and more thorough preoperative
      sterilization procedures during these warmer months. 

PMID- 24679207
TI  - Proximal femoral reconstruction with a constrained acetabulum in oncologic
      patients.
AB  - Metallic endoprostheses are used for oncological reconstruction around the
      proximal femur and hip joint. Common modes of failure with hemiarthroplasty or
      standard hip arthroplasty after proximal femoral replacement include dislocation,
      late hip pain, and infection. The authors reviewed hospital records to identify
      patients undergoing constrained tripolar hip arthroplasty for oncological reasons
      between 2002 and 2012. Inclusion criterion was at least 12-cm proximal femoral
      resection, including patients with total femur reconstruction. A total of 33
      patients were reviewed. Information regarding demographics, length of follow-up,
      treatment characteristics, and patient outcomes was extracted. Average follow-up
      for all patients was 912.33 days (30.4 months). Average follow-up was 1396.1 days
      for living patients and 428.6 days for deceased patients. Average estimated blood
      loss was 462.12 cc: an average of 1080 cc for patients undergoing total femoral
      resection and replacement and 315.8 cc for patients undergoing proximal femoral
      resection and replacement. Average operative time was 137.7 minutes: an average
      of 205 minutes for patients undergoing total femoral resection and replacement
      and 119.1 minutes for patients undergoing proximal femoral resection and
      replacement. Average Musculoskeletal Tumor Society score was 21.7. There were no
      dislocations in the cohort. A constrained tripolar device can be safely used for
      oncological proximal femoral reconstructions while minimizing the risk of
      dislocation. Positioning of the acetabular implant in neutral anatomic version in
      conjunction with a neutral-placed femoral component provides the greatest range
      of motion, reduction of liner impingement, and improved hip stability. 

PMID- 24679208
TI  - Assessment of mortality risk in elderly patients after proximal femoral fracture.
AB  - Mortality after hip fracture is a major problem in the Western world, but its
      mechanisms remain uncertain. This study assessed the 2-year mortality rate after
      hip fracture in elderly patients by including hospital factors (eg, intervention
      type, surgical delay), underlying health conditions, and, for a subset, lifestyle
      factors (eg, body mass index, smoking, alcohol). A total of 828 patients (183
      men) 70 to 99 years old experiencing a hip fracture in 2009 in the province of
      Varese were included in the study. The risk factors for death were assessed
      through Kaplan-Meier analysis and Cox proportional hazards analysis. Hip fracture
      incidence per 1000 persons was higher in women (8.4 vs 3.7 in men) and in elderly
      patients (12.4 for 85-99 years vs 4.4 for 70-84 years). The mortality rate after
      1, 6, 12, and 24 months was 4.7%, 16%, 20.7%, and 30.4%, respectively. For the
      province of Varese, sex (hazard ratio, 0.39 for women), age group (hazard ratio,
      2.2 for 85-99 years), and Charlson Comorbidity Index score (hazard ratio, 2.06
      for score greater than 1) were found to be statistically significant. The 2-year
      mortality rate in hip fractures is associated with sex, age, and comorbidities.
      Male sex, age older than 85 years, and Charlson Comorbidity Index score greater
      than 1 are associated with a higher risk. Surgical delay was significant in the
      Kaplan-Meier survival time analysis but not in the Cox hazard analysis,
      suggesting that early surgery reduces risk in patients with numerous
      comorbidities. 

PMID- 24679209
TI  - Treatment of humeral shaft aseptic nonunions in elderly patients with opposite
      structural allograft, BMP-7, and mesenchymal stem cells.
AB  - Humeral shaft aseptic nonunions occur in 2% to 10% of patients managed
      conservatively and 10% to 15% of patients treated surgically. The complex
      muscular and neurovascular anatomy of the upper limb makes the surgical approach
      to the fracture site demanding and risky, especially when previous surgeries have
      been attempted. The clinical consequence of atrophic humeral shaft nonunions is a
      severe functional limitation that may significantly affect activities of daily
      living, especially in the elderly. The surgical treatment of humeral shaft
      nonunions is challenging for orthopedic surgeons. Patients with atrophic
      nonunions require both a stable fixation and enhancement of the biologic response
      because of the weak biologic reaction observed at the fracture site. The gold
      standard of treatment in elderly patients has not been described. Nonetheless,
      older age and comorbidities are associated with potentially malignant nonunions.
      This study reports the authors' experience using opposite cortical allograft
      combined with bone morphogenetic protein 7 and mesenchymal stem cells to treat
      humeral shaft atrophic nonunions in 2 elderly patients. The nonunion site healed
      at 4 months (patient 1) and 8 months (patient 2) postoperatively, with full
      return to activities of daily living and no pain. Neither patient reported
      complications of the radial nerve, which is at high risk of injury during this
      type of surgery. The only reported complication (patient 2) was an intraoperative
      longitudinal partial distal humeral fracture, probably caused by compression
      screw overtightening. The use of a locking plate and opposite cortical allograft,
      combined with BMP-7 and mesenchymal stem cells, represents a safe and effective
      treatment for malignant nonunions in older patients. 

PMID- 24679210
TI  - Ankylosing spondylitis in an athlete with chronic sacroiliac joint pain.
AB  - Ankylosing spondylitis is a disease in which inflammation of joints, most often
      in the axial skeleton, can lead to reactive fibrosis and eventual joint fusion
      with associated immobility and kyphosis. The disease often involves extra
      articular features, such as uveitis and aortic regurgitation, as well as
      associated inflammatory conditions of the intestines. Its etiology is unknown.
      Ankylosing spondylitis most commonly presents in young males (15-30 years old) as
      persistent low back pain and stiffness that is worse in the morning and at night
      and improves with activity. The authors report the case of a young male athlete
      whose symptoms were initially incorrectly diagnosed as sacroiliac joint
      instability and dysfunction and later as a sacroiliac stress fracture before
      further workup revealed a seronegative spondyloarthropathy and the diagnosis of
      ankylosing spondylitis. The patient was prescribed oral indomethacin daily by the
      attending rheumatologist and started on a slow progression of return to running,
      jumping, and weight lifting. Within 4 weeks of beginning this treatment, the
      patient had complete cessation of pain with the medication. At follow-up 1 year
      after graduation from his university, the patient was nearly symptom free and
      working in a non-heavy labor job. The purpose of this case report is to remind
      sports medicine physicians of the prevalence of rheumatologic diseases in general
      and ankylosing spondylitis in particular and of the various ways in which
      spondyloarthropathies may present in athletes. Increased suspicion may lead to
      earlier diagnosis and treatment, potentially reducing illness severity and
      duration and improving the performance of athletes with this condition. 

PMID- 24679211
TI  - Loosening of the patellar component and extra-articular and transcutaneous
      migration after TKA.
AB  - Replacement of the patella during total knee arthroplasty (TKA) remains
      controversial. Despite some attempts to establish guidelines for this procedure,
      there is still no consensus in the literature. When the patella is replaced, the
      patient is subjected to certain complications, including loosening of the
      component. The loosened patellar component most commonly migrates to the intra
      articular region of the knee. However, there have been a few reports of migration
      of the component to the extra-articular region, particularly when release of the
      lateral retinaculum and osteonecrosis of the patella are involved. The authors
      report a case of patellar component loosening and extra-articular and
      transcutaneous migration of the component 9 years after TKA. This report is
      unique because, during the primary procedure, no lateral release was performed
      and no patellar necrosis was evident on radiographs. The component was removed in
      the operating room and the wound cleaned and closed. Because of the probable slow
      migration of the component, there was no communication between the external
      environment and the joint at the time of surgery. There were no further
      complications after the wound healed. This case emphasizes the need for periodic
      radiographic follow-up after TKA. 

PMID- 24679212
TI  - Intra-articular osteoid osteoma of the proximal ulna.
AB  - Osteoid osteoma is a common benign osteogenic bone neoplasm characterized
      histologically by increased osteoid tissue formation with an intracortical nidus
      surrounded by cortical thickening and vascular fibrous stroma and sclerosis. The
      clinical presentation classically includes severe nocturnal pain that is improved
      with nonsteroidal anti-inflammatory drugs. Younger men (second and third decades)
      have the highest incidence, with the most frequent sites of involvement being the
      long bones or axial skeleton. Osteoid osteoma may be missed due to the lesion
      occurring in an atypical location or due to failure to obtain advanced imaging
      studies such as computed tomography (CT). Intralesional or wide excision, or CT
      guided radiofrequency ablation if available, leads to predictable and rapid pain
      relief. The authors report the case of a 24-year-old man who had a painful
      flexion contracture of his dominant right elbow for 1.5 years, secondary to an
      intra-articular osteoid osteoma. Attempted motion, passive or active, produced a
      marked exacerbation of pain. Previous surgeries, including an elbow synovectomy
      and an ulnar nerve transposition, had been unsuccessful in relieving his pain.
      Plain radiographs demonstrated a small area of periosteal thickening adjacent to
      the sublime tubercle. Fine-cut CT scan demonstrated an osteoid osteoma within the
      articular surface of the trochlear notch of the olecranon, adjacent to the
      sublime tubercle. Because of a perceived risk to the surrounding articular
      cartilage, CT-guided radiofrequency ablation was not performed. Wide en bloc
      surgical excision of the nidus was performed, with complete resolution of pain
      and rapid return to normal function. 

PMID- 24679213
TI  - Osteochondritis dissecans of the lateral tibial condyle associated with agenesis
      of both cruciate ligaments.
AB  - Osteochondritis dissecans is a rare cause of painful knees in children. Only 10
      cases of lateral tibial condyle involvement have been reported in the literature.
      Congenital agenesis of both cruciate ligaments has been described even less, and
      its prevalence is unknown. The authors report an atypical association of
      osteochondritis dissecans of the tibia with congenital absence of both cruciate
      ligaments. A 12-year-old male soccer player presented with a painful right knee.
      Magnetic resonance imaging revealed the diagnosis. The child was treated
      conservatively. At 18-month follow-up, radiographs showed osseointegration of the
      osteochondritis dissecans, and the patient had resumed normal athletic activity
      without pain. To the authors' knowledge, this is the only report describing such
      an association. The authors discuss the possible etiology of osteochondritis
      dissecans associated with agenesis of the cruciate ligaments and highlight the
      possibility of this association when osteochondritis dissecans of the tibia is
      diagnosed in a child with a painful knee. In this patient, the strain due to
      anteroposterior instability may have been the cause of osteochondritis.
      Conservative treatment should be considered in this setting. 

PMID- 24679214
TI  - Indicators for detection of septic arthritis in the acutely swollen joint cohort
      of those without joint prostheses.
AB  - Differentiating septic arthritis from culture-negative, acute atraumatic joint
      effusion is difficult. Studies have attempted to elucidate factors that herald
      infection, but, due to overlap, most conclude that the diagnosis ultimately
      relies on clinical judgment. Furthermore, studies are limited by broad inclusion
      criteria. The current retrospective case study sought to examine (1) which
      markers differentiate a culture-positive septic joint from culture-negative
      effusion in patients suspicious for infection despite no growth on Gram stain and
      without previous surgery in the affected joint and (2) whether threshold values
      of these markers exist that predict septic arthritis. The study was performed by
      reviewing records of those who underwent operative irrigation and debridement
      involving the shoulder, elbow, wrist, hip, knee, and ankle. Patients were
      included if they were older than 18 years and had an acutely swollen/painful
      joint and no organisms on initial Gram stain. Exclusion criteria were lack of
      serum markers or synovial fluid aspirate, antibiotics within 1 week, adjacent
      wound or skin infection, recent trauma to the joint, and previous joint infection
      or surgery to the joint. Several clinical, serological, and synovial parameters
      were collected and analyzed using paired t test with Bonferonni correction. Serum
      C-reactive protein was the only significantly different variable between groups.
      Serum C-reactive protein greater than 10.5 mg/dL was predictive of infection. In
      those suspicious for infection despite no growth on Gram stain and without
      previous surgery in the affected joint, C-reactive protein greater than 10.5
      mg/dL is suspicious for joint sepsis and should warrant consideration for urgent
      irrigation and debridement. 

PMID- 24679215
TI  - Quantitative evaluation of colloidal stability of antibody solutions using PEG
      induced liquid-liquid phase separation.
AB  - Colloidal stability of antibody solutions, i.e., the propensity of the folded
      protein to precipitate, is an important consideration in formulation development
      of therapeutic monoclonal antibodies. In a protein solution, different pathways
      including crystallization, colloidal aggregation, and liquid-liquid phase
      separation (LLPS) can lead to the formation of precipitates. The kinetics of
      crystallization and aggregation are often slow and vary from protein to protein.
      Due to the diverse mechanisms of these protein condensation processes, it is a
      challenge to develop a standardized test for an early evaluation of the colloidal
      stability of antibody solutions. LLPS would normally occur in antibody solutions
      at sufficiently low temperature, provided that it is not preempted by freezing of
      the solution. Poly(ethylene glycol) (PEG) can be used to induce LLPS at
      temperatures above the freezing point. Here, we propose a colloidal stability
      test based on inducing LLPS in antibody solutions and measuring the antibody
      concentration of the dilute phase. We demonstrate experimentally that such a PEG
      induced LLPS test can be used to compare colloidal stability of different
      antibodies in different solution conditions and can be readily applied to high
      throughput screening. We have derived an equation for the effects of PEG
      concentration and molecular weight on the results of the LLPS test. Finally, this
      equation defines a binding energy in the condensed phase, which can be determined
      in the PEG-induced LLPS test. This binding energy is a measure of attractive
      interactions between antibody molecules and can be used for quantitative
      characterization of the colloidal stability of antibody solutions. 

PMID- 24679216
TI  - Maternal-embryo interaction leading up to the initiation of implantation of
      pregnancy in cattle.
AB  - Early embryo development following fertilization occurs in the oviduct. However,
      despite being the site of fertilization in cattle, it is possible to by-pass the
      oviduct by producing embryos in vitro and/or by transferring blastocysts
      recovered from one female into the uterus of another. While there is substantial
      evidence for the oviduct having an influence on the quality of the developing
      embryo, manifested in altered morphology, gene expression and cryotolerance,
      evidence for a two-way dialogue is weak. In contrast, successful growth and
      development of the post-hatching blastocyst and pregnancy establishment are a
      result of the two-way interaction between a competent embryo and a receptive
      uterine environment. Progesterone (P4) plays a key role in reproductive events
      associated with establishment and maintenance of pregnancy through its action on
      the uterine endometrium. Elevated concentrations of circulating P4 in the
      immediate post-conception period have been associated with an advancement of
      conceptus elongation, an increase in interferon-tau production and, in some
      studies, higher pregnancy rates in cattle. This review summarizes current
      knowledge on the communication between the developing embryo and the maternal
      reproductive tract. 

PMID- 24679217
TI  - Purification and partial characterization of an acidic alpha-amylase from a newly
      isolated Bacillus subtilis ZJ-1 that may be applied to feed enzyme.
AB  - An amylase-producing strain was isolated from soy sauce and designated as
      Bacillus subtilis ZJ-1. Purification of alpha-amylase from B. subtilis ZJ-1 to
      homogeneity by ethanol fractionation, ultrafiltration, and Sephadex G-100 gel
      filtration resulted in recovery of 8.9% and a specific activity of 542.7 U/mg
      protein. The molecular mass was estimated to be 58 kD by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme reached its maximum
      activity at a pH of 5.0 and a temperature of 50 degrees C. The enzyme remained at
      89.4 +/- 3.0% of its activity at 40 degrees C. The enzyme retained 87.7 +/- 3.7%
      and 63.4 +/- 2.9% of its original activity at 40 degrees C after a 60-min
      incubation in the presence of 5 mM CaCl2 at a pH of 5.0 and 4.0, respectively.
      These properties indicate that the novel enzyme has a theoretically high survival
      rate and excellent starch catalytic efficiency in the typical chicken
      gastrointestinal-tract environment (pH 3.5-7.0, 40 degrees C). In addition, the
      enzyme remained at 78.4 +/- 3.6% of its activity after a 5-min incubation at 80
      degrees C, which demonstrates that the enzyme could maintain a high survival rate
      in the pelleting process of feed production. The characteristics just described
      make this enzyme a good candidate for use as a chicken feed enzyme. 

PMID- 24679218
TI  - A chemoselective route to beta-enamino esters and thioesters.
AB  - Conditions were developed for syntheses of beta-enamino esters, thioesters, and
      amides. These reactions involve hydroxybenzotriazole derivatives in buffered
      media. Illustrative syntheses of some heterocyclic systems are given, including
      some related to protein-protein interface mimics. 

PMID- 24679219
TI  - Increased inequality in mortality from road crashes among Arabs and Jews in
      Israel.
AB  - OBJECTIVE: Previous studies in several countries have shown that the economically
      disadvantaged seem to have a greater risk of being involved in a car crash. The
      aim of the present study was to compare rates and trends in mortality and injury
      from road crashes by age among the Arab and Jewish populations in Israel.
      METHODS: Data on road crashes with casualties (2003-2011) from the Israeli
      Central Bureau of Statistics were analyzed. Age-adjusted road crash injury rates
      and mortality rates for 2003 to 2011 were calculated and time trends for each age
      group and population group are presented. Time trend significance was evaluated
      by linear regression models. RESULTS: Arabs in Israel are at increased risk of
      injury and mortality from road crashes compared to Jews. Road crash injury rates
      have significantly decreased in both populations over the last decade, although
      the rates have been persistently higher among Arabs. Road crash mortality rates
      have also decreased significantly in the Jewish population but not in the Arab
      population. This implies an increase in the disparity in mortality between Jews
      and Arabs. The most prominent differences in road crash injury and mortality
      rates between Arabs and Jews can be observed in young adults and young children.
      CONCLUSIONS: The reduction in road crashes in the last decade is a positive
      achievement. However, the reductions are not equal among Arabs and Jews in
      Israel. Therefore, an increase in the disparities in mortality from road crashes
      is apparent. Public health efforts need to focus specifically on decreasing road
      crashes in the Arab community.

PMID- 24679221
TI  - Antibody modified gold nanoparticles for fast and selective, colorimetric T7
      bacteriophage detection.
AB  - Herein, we report a colorimetric immunosensor for T7 bacteriophage based on gold
      nanoparticles modified with covalently bonded anti-T7 antibodies. The new
      immunosensor allows for a fast, simple, and selective detection of T7 virus. T7
      virions form immunological complexes with the antibody modified gold
      nanoparticles which causes them to aggregate. The aggregation can be observed
      with the naked eye as a color change from red to purple, as well as with a UV-vis
      spectrophotometer. The aggregate formation was confirmed with SEM imaging. Sensor
      selectivity against the M13 bacteriophage was demonstrated. The limit of
      detection (LOD) is 1.08 * 10(10) PFU/mL (18 pM) T7. The new method was compared
      with a traditional plaque test. In contrast to biological tests the colorimetric
      method allows for detection of all T7 phages, not only those biologically active.
      This includes phage ghosts and fragments of virions. T7 virus has been chosen as
      a model organism for adenoviruses. The described method has several advantages
      over the traditional ones. It is much faster than a standard plaque test. It is
      more robust since no bacteria-virus interactions are utilized in the detection
      process. Since antibodies are available for a large variety of pathogenic
      viruses, the described concept is very flexible and can be adapted to detect many
      different viruses, not only bacteriophages. Contrary to the classical
      immunoassays, it is a one-step detection method, and no additional amplification,
      e.g., enzymatic, is needed to read the result. 

PMID- 24679220
TI  - A transgenic zebrafish model for monitoring glucocorticoid receptor activity.
AB  - Gene regulation resulting from glucocorticoid receptor and glucocorticoid
      response element interactions is a hallmark feature of stress response signaling.
      Imbalanced glucocorticoid production and glucocorticoid receptor activity have
      been linked to socioeconomically crippling neuropsychiatric disorders, and
      accordingly there is a need to develop in vivo models to help understand disease
      progression and management. Therefore, we developed the transgenic SR4G zebrafish
      reporter line with six glucocorticoid response elements used to promote
      expression of a short half-life green fluorescent protein following
      glucocorticoid receptor activation. Herein, we document the ability of this
      reporter line to respond to both chronic and acute exogenous glucocorticoid
      treatment. The green fluorescent protein expression in response to transgene
      activation was high in a variety of tissues including the brain, and provided
      single-cell resolution in the effected regions. The specificity of these
      responses is demonstrated using the partial agonist mifepristone and mutation of
      the glucocorticoid receptor. Importantly, the reporter line also modeled the
      temporal dynamics of endogenous stress response signaling, including the
      increased production of the glucocorticoid cortisol following hyperosmotic stress
      and the fluctuations of basal cortisol concentrations with the circadian rhythm.
      Taken together, these results characterize our newly developed reporter line for
      elucidating environmental or genetic modifiers of stress response signaling,
      which may provide insights to the neuronal mechanisms underlying neuropsychiatric
      disorders such as major depressive disorder. 

PMID- 24679223
TI  - Chronotype and sleep duration: the influence of season of assessment.
AB  - Little is known about human entrainment under natural conditions, partly due to
      the complexity of human behavior, torn between biological and social time and
      influenced by zeitgebers (light-dark cycles) that are progressively "polluted"
      (and thereby weakened) by artificial light. In addition, data about seasonal
      variations in sleep parameters are scarce. We, therefore, investigated seasonal
      variation in cross-sectional assessments of sleep/wake times of 9765 subjects
      from four European populations (EGCUT = Estonian Genome Centre, University of
      Tartu in Estonia; KORA = Cooperative Health Research in the Region of Augsburg in
      Germany; KORCULA = The Korcula study in Croatia; and ORCADES = The Orkney Complex
      Disease Study in Scotland). We identified time-of-year dependencies for the
      distribution of chronotype (phase of entrainment assessed as the mid-sleep time
      point on free days adjusted for sleep deficit of workdays) in cohorts from
      Estonia (EGCUT) and Germany (KORA). Our results indicate that season (defined as
      daylight saving time - DST and standard zonetime periods - SZT) specifications of
      photoperiod influence the distribution of chronotype (adjusted for age and sex).
      Second, in the largest investigated sample, from Estonia (EGCUT; N = 5878), we
      could detect that seasonal variation in weekly average sleep duration was
      dependent on individual chronotype. Later chronotypes in this cohort showed
      significant variation in their average sleep duration across the year, especially
      during DST (1 h advance in social time from the end of March to end of October),
      while earlier chronotypes did not. Later chronotypes not only slept less during
      the DST period but the average chronotype of the population assessed during this
      period was earlier than during the SZT (local time for a respective time zone)
      period. More in detail, hierarchical multiple regression analyses showed that,
      beyond season of assessment (DST or SZT), social jetlag (SJl; the discrepancy
      between the mid sleep on free and work days - which varied with age and sex)
      contributed to a greater extent to the variation in sleep duration than
      chronotype (after taking into account factors that are known to influence sleep
      duration, i.e. age, sex and body mass index). Variation in chronotype was also
      dependent on age, sex, season of assessment and SJl (which is highly correlated
      with chronotype - SJl was larger among later chronotypes). In summary, subjective
      assessments of sleep/wake times are very reliable to assess internal time and
      sleep duration (e.g. reproducing sleep duration and timing tendencies related to
      age and sex across the investigated populations), but season of assessment should
      be regarded as a potential confounder. We identified in this study photoperiod
      (seasonal adaptation) and SJl as two main factors influencing seasonal variation
      in chronotype and sleep duration. In conclusion, season of assessment, sex and
      age have an effect on epidemiological variation in sleep duration, chronotype and
      SJl, and should be included in studies investigating associations between these
      phenotypes and health parameters, and on the development of optimal prevention
      strategies. 

PMID- 24679224
TI  - Daily fluctuations in attention at school considering starting time and
      chronotype: an exploratory study.
AB  - Interest to investigate daily fluctuations in cognitive tasks, so-called "school
      rhythms", lies in exploring the most favourable time-of-day for learning
      considering the analysis of variations in performance taking into account
      individual differences. The aim of this study was to describe daily fluctuations
      in attention at three different times of the school day, two different days,
      considering chronotype and three different school start times (08:00, 08:15 and
      08:30 h). Participants were 669 adolescents aged 12-16. Sleep length and
      inductive reasoning were considered as covariates. In general, attention
      increased throughout the school day, boys reached higher attention than girls
      and, moreover, evening type boys reached higher attention than evening type
      girls. No differences between chronotypes were observed. When students were
      familiar with the task, chronotype, sex and time-of-day interactions seem to be
      important factors to consider.

PMID- 24679225
TI  - Nocturnal melatonin regulation in post-traumatic vegetative state: a possible
      role for melatonin supplementation?
AB  - Circadian rhythms were recently proposed as a measure of physiological state and
      prognosis in disorders of consciousness (DOC). So far, melatonin regulation was
      never assessed in vegetative state (VS). Aim of our research was to investigate
      the nocturnal melatonin levels and light-induced melatonin suppression in a
      cohort of VS patients. We assessed six consecutive patients (four men, age 33.3
      +/- 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers
      (five men, age 34.3 +/- 8.9 years) on two consecutive nights: one baseline and
      one light exposure night. During baseline, night subjects were in bed in a dim
      (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30
      am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting
      was used for melatonin suppression test night, except for the exposure to
      monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were
      evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by
      melatonin suppression score (caMSS) and suppression rate. We searched for group
      differences in melatonin levels, differences between repeated samples melatonin
      concentrations during baseline night and light exposure night, and light-induced
      suppression of melatonin secretion. During baseline night, controls showed an
      increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes
      were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was
      significantly lower in VS vs controls (p = 0.036). During light-exposure night,
      controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2,
      p = 0.016 and 0.002, respectively), while VS patients displayed no significant
      changes. The magnitude of light-induced suppression of melatonin levels was
      statistically different between groups considering control adjusted caMSS (p =
      0.000), suppression rate (p = 0.002) and absolute percentage difference (p =
      0.012). These results demonstrate for the first time that VS patients present an
      alteration in night melatonin secretion and reduced light-induced melatonin
      suppression. These findings confirm previous studies demonstrating a disruption
      of the circadian system in DOC and suggest a possible benefit from melatonin
      supplementation in VS. 

PMID- 24679226
TI  - Could mean platelet volume be a promising biomarker of progression of chronic
      kidney disease?
AB  - The mean platelet volume (MPV), a readily available indicator of platelet
      activation and function, is a useful predictive and prognostic biomarker of
      cardiovascular and cerebrovascular disease (CVD). It is associated with a variety
      of prothrombotic and proinflammatory diseases. Larger platelets are more likely
      to aggregate and release greater quantities of adhesive molecules. MPV has seldom
      been investigated in patients with chronic kidney disease (CKD). This study aimed
      to investigate the relationship between MPV levels and the glomerular filtration
      rate (GFR) in patients with CKD. We reviewed the medical records of patients with
      CKD who visited the nephrology outpatient clinics of Soonchunhyang University
      Bucheon Hospital between January 2010 and May 2013. A total of 553 patients were
      included in the present retrospective study. According to the estimated GFR
      (eGFR) calculated by the abbreviated the Modification of Diet in Renal Disease
      (MDRD) equation, the patients were allocated to Group 1 (GFR, 60-89
      ml/minute/1.73 m(2); n = 64), Group 2 (GFR, 30-59 ml/minute/1.73 m(2); n = 268),
      Group 3 (GFR, 15-29 ml/minute/1.73 m(2); n = 147), or Group 4 (GFR, <15
      ml/minute/1.73 m(2) and non-dialysis; n = 74). Data were analyzed by Student's t
      test, the chi-squared test, Pearson's correlation coefficient (r), Tukey's
      honestly significant difference (HSD) test, and one-way analysis of covariance.
      The MPV values had a negative correlation with eGFR in patients with CKD
      (Pearson's correlation coefficient = -0.553, p < 0.001). The mean MPV values in
      Groups 1-4 were 9.81 +/- 0.13 fl, 10.34 +/- 0.08 fl, 10.86 +/- 0.09 fl, and 11.19
      +/- 0.11 fl, respectively (p < 0.001). Multiple comparisons of MPV values in the
      four groups by Tukey's HSD test showed statistically significant intergroup
      differences, with all p values <0.001. Platelet counts and PDW decreased along
      with eGFR, and there were no significant differences with respect to
      plateletcrit. Patients with prevalent coronary artery disease (CAD) or CVD had
      higher MPVs than did those without CAD or CVD. MPV was significantly increased
      with progression of CKD. MPV may be a useful indicator of increased risks of CAD
      or CVD in patients with CKD.

PMID- 24679227
TI  - Possible roles of insulin signaling in osteoblasts.
AB  - Insulin and its downstream signaling pathway are indispensable for postnatal bone
      growth and turnover by having influence on both osteoblast and osteoclast
      development. Insulin signaling regulates both bone formation by osteoblasts and
      bone resorption by osteoclasts; however, the regulation occurs mainly through the
      insulin signaling pathway within osteoblasts. An impairment of osteoblastic
      insulin signaling leads to an impaired bone quality by affecting osteoblast
      proliferation, differentiation and survival. The insulin signaling pathway and
      MAPK and PI3K/Akt pathways play pivotal roles in the differentiation, function
      and survival of bone cells. Current evidence suggests that osteoblastic insulin
      signaling not only modulates bone growth and turnover but is also required for
      energy metabolism. Several mice models with impaired insulin signaling exhibited
      both bone and metabolic phenotypes, including symptoms of low bone mass, obesity,
      glucose intolerance and insulin resistance. In this review, we discuss the key
      findings that suggest a pivotal role of osteoblastic insulin signaling in both
      bone and energy metabolism.

PMID- 24679222
TI  - A randomised controlled trial of the clinical effectiveness and cost
      effectiveness of different knee prostheses: the Knee Arthroplasty Trial (KAT).
AB  - BACKGROUND: In the late 1990s, new developments in knee replacement were
      identified as a priority for research within the NHS. The newer forms of
      arthroplasty were more expensive and information was needed on their safety and
      cost-effectiveness. OBJECTIVES: The Knee Arthroplasty Trial examined the clinical
      effectiveness and cost-effectiveness of four aspects of knee replacement surgery:
      patellar resurfacing, mobile bearings, all-polyethylene tibial components and
      unicompartmental replacement. DESIGN: This study comprised a partial factorial,
      pragmatic, multicentre randomised controlled trial with a trial-based cost
      utility analysis which was conducted from the perspective of the NHS and the
      patients treated. Allocation was computer generated in a 1 : 1 ratio using a
      central system, stratified by eligible comparisons and surgeon, minimised by
      participant age, gender and site of disease. Surgeons were not blinded to
      allocated procedures. Participants were unblinded if they requested to know the
      prosthesis they received. SETTING: The setting for the trial was UK secondary
      care. PARTICIPANTS: Patients were eligible for inclusion if a decision had been
      made for them to have primary knee replacement surgery. Patients were recruited
      to comparisons for which the surgeon was in equipoise about which type of
      operation was most suitable. INTERVENTIONS: Patients were randomised to receive a
      knee replacement with the following: patellar resurfacing or no patellar
      resurfacing irrespective of the design of the prosthesis used; a mobile bearing
      between the tibial and femoral components or a bearing fixed to the tibial
      component; a tibial component made of either only high-density polyethylene ('all
      polyethylene') or a polyethylene bearing fixed to a metal backing plate with
      attached stem; or unicompartmental or total knee replacement. MAIN OUTCOME
      MEASURES: The primary outcome was the Oxford Knee Score (OKS). Other outcomes
      were Short Form 12; EuroQol 5D; intraoperative and postoperative complications;
      additional surgery; cost; and cost-effectiveness. Patients were followed up for a
      median of 10 years; the economic evaluation took a 10-year time horizon,
      discounting costs and quality-adjusted life-years (QALYs) at 3.5% per annum.
      RESULTS: A total of 116 surgeons in 34 centres participated and 2352 participants
      were randomised: 1715 in patellar resurfacing; 539 in mobile bearing; 409 in all
      polyethylene tibial component; and 34 in the unicompartmental comparisons. Of
      those randomised, 345 were randomised to two comparisons. We can be more than 95%
      confident that patellar resurfacing is cost-effective, despite there being no
      significant difference in clinical outcomes, because of increased QALYs [0.187;
      95% confidence interval (CI) -0.025 to 0.399] and reduced costs (-L104; 95% CI 
      L630 to L423). We found no definite advantage or disadvantage of mobile bearings
      in OKS, quality of life, reoperation and revision rates or cost-effectiveness. We
      found improved functional results for metal-backed tibias: complication,
      reoperation and revision rates were similar. The metal-backed tibia was cost
      effective (particularly in the elderly), costing L35 per QALY gained.
      CONCLUSIONS: The results provide evidence to support the routine resurfacing of
      the patella and the use of metal-backed tibial components even in the elderly.
      Further follow-up is required to assess the stability of these findings over time
      and to inform the decision between mobile and fixed bearings. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN45837371. FUNDING: This project was funded by the
      NIHR Health Technology Assessment programme and the orthopaedic industry. It will
      be published in full in Health Technology Assessment; Vol. 18, No. 19. See the
      NIHR Journals Library website for further project information.

PMID- 24679228
TI  - Expanding indications for ESD: mucosal disease (upper and lower gastrointestinal
      tract).
AB  - Endoscopic resection is now considered a curative procedure for early gastric
      cancer. In Japan, it has increasingly replaced surgical resection for this
      indication, although in the West it has not been universally accepted as a first
      line treatment. Recently, endoscopic submucosal dissection has been increasingly
      applied to colorectal disease, although it has not become a standard therapeutic
      procedure for early colorectal carcinoma because of its technical difficulty, the
      relatively long procedure time required, and the risk of complications, such as
      perforation and bleeding. 

PMID- 24679229
TI  - Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors).
AB  - Endoscopic submucosal dissection (ESD) is useful for submucosal tumors (SMTs)
      within the superficial submucosal layer, but perforation frequently occurs during
      ESD for SMTs located at the deeper layer. Endoscopic resection for small
      esophageal SMTs is acceptable, although candidates for endoscopic removal are
      rare. Laparoscopic assistance will be effective for minimally invasive endoscopic
      local resection for certain types of gastric SMT. Endoscopic mucosal resection
      with a ligation device would be better than ESD for rectal carcinoid in terms of
      simplicity and effectiveness. 

PMID- 24679230
TI  - Electrocautery for ESD: settings of the electrical surgical unit VIO300D.
AB  - An electrical surgical unit (ESU) performs incisions and coagulation through
      applying Joule heat, generated by a high-frequency current onto tissue without
      neuromuscular stimulation. Output by the ESU includes incision output and
      coagulation output. Incision output is needed to generate a steam explosion
      (spark) by quickly increasing the intracellular fluid temperature through
      continuous application of Joule heat generated by the high-frequency current
      (unmodulated pulse: continuous wave). To perform safe and successful endoscopic
      submucosal dissection, one must fully understand the principles and features of
      an ESU to use settings that match the device and to adjust the settings
      appropriately for each situation. 

PMID- 24679231
TI  - Endoscopic submucosal dissection (ESD) versus simplified/hybrid ESD.
AB  - The development of endoscopic submucosal dissection (ESD) has enabled en bloc
      resection of lesions regardless of size and shape. However, ESD of colorectal
      tumors is technically difficult. Early stage colorectal tumors can be removed by
      endoscopic mucosal resection (EMR) but larger tumors may require piecemeal
      resection. Therefore, ESD with snaring has been proposed for more reliable EMR
      and easier ESD. This is a good option to fill the gap between EMR and ESD, and a
      good step to the introduction of full ESD. 

PMID- 24679232
TI  - Esophageal ESD: technique and prevention of complications.
AB  - The advantage of endoscopic submucosal dissection (ESD) is the ability to achieve
      high R0 resection, providing low local recurrence rate. Esophageal ESD is
      technically more difficult than gastric ESD due to the narrower space of the
      esophagus for endoscopic maneuvers. Also, the risk of perforation is higher
      because of the thin muscle layer of the esophageal wall. Blind dissection should
      be avoided to prevent perforation. A clip with line method is useful to keep a
      good endoscopic view with countertraction. Only an operator who has adequate
      skill should perform esophageal ESD. 

PMID- 24679233
TI  - Gastric ESD: current status and future directions of devices and training.
AB  - Endoscopic mucosal resection (EMR) of early gastric cancer, which has been proved
      to be safe and effective and is the established standard of care in Japan, has
      become increasingly established worldwide in the past decade. Endoscopic
      submucosal dissection (ESD) is superior to EMR, as it is designed to provide
      precise pathologic staging and long-term curative therapy based on an en bloc R0
      specimen irrespective of the size and/or location of the tumor. However, ESD
      requires highly skilled and experienced endoscopists. The introduction of ESD to
      the Western world necessitates collaborations between Eastern and Western
      endoscopists, pathologists, and surgeons. 

PMID- 24679234
TI  - Duodenal ESD: conquering difficulties.
AB  - Duodenal endoscopic submucosal dissection (ESD) is technically difficult due to
      the unique anatomic features. The risks include intraprocedural complications,
      delayed bleeding, and perforation. A small-caliber-tip transparent hood is
      useful. Mechanical stretching of the submucosal tissue allows safe dissection and
      effective prevention of bleeding with minimum muscle injury under direct
      visualization of the submucosal tissue and blood vessels. A short double-balloon
      endoscope is useful to stabilize control of the endoscope tip in distal duodenal
      ESD. Selection of ESD in the duodenum should be made cautiously considering both
      benefits and risks of the procedure. 

PMID- 24679235
TI  - Colorectal ESD: current indications and latest technical advances.
AB  - The number of medical facilities that perform colorectal endoscopic submucosal
      dissection (ESD) has been growing, and its effectiveness has been increasingly
      reported in recent years. Indications approved by the Japanese government's
      medical insurance system are early colorectal cancers with a maximum tumor size
      of 2-5 cm. ESD was an effective procedure for treating noninvasive colorectal
      tumors difficult to resect en bloc by conventional EMR, resulting in a higher en
      bloc resection rate that is less invasive than surgery. Based on the excellent
      clinical results of colorectal ESDs, the Japanese health care insurance system
      has approved colorectal ESD for coverage. 

PMID- 24679236
TI  - Submucosal endoscopy: from ESD to POEM and beyond.
AB  - Peroral endoscopic myotomy (POEM) is an evolving minimally invasive endoscopic
      surgical procedure, with no skin incision, intended for long-term recovery from
      symptoms of esophageal achalasia. POEM was developed based on both the already
      established surgical principles of esophageal myotomy and the advanced techniques
      of endoscopic submucosal dissection. This article relates how POEM was developed,
      and its use in practice is reported and discussed. As an extension of the POEM
      technique, submucosal endoscopic tumor resection is introduced. 

PMID- 24679237
TI  - Investigating deeper: muscularis propria to natural orifice transluminal
      endoscopic surgery.
AB  - Submucosal endoscopy with a mucosal flap (SEMF) safety valve technique is a
      global concept in which the submucosa is a free working space for endoscopic
      interventions. A purposefully created intramural space provides an endoscopic
      access route to the deeper layers and into the extraluminal cavities. The mucosa
      overlying the intramural space is protective, reducing contamination during
      natural orifice transluminal endoscopic surgery (NOTES) procedures and providing
      a sealant flap to repair the entry point and the submucosal space. In addition to
      NOTES, SEMF enables endoscopic achalasia myotomy, histologic analysis of the
      muscularis propria, and submucosal tumor removal. 

PMID- 24679238
TI  - Regenerative medicine: tissue-engineered cell sheet for the prevention of post
      esophageal ESD stricture.
AB  - Induced pluripotent stem (iPS) cells have captured the world's attention and
      directed an unprecedented focus on regenerative medicine. The potential of iPS
      cells to aid in the development of new treatments for various diseases is
      exciting, and researchers are only beginning to discover their potential benefits
      for humans. iPS cells are more effective if they are interconnected with tissues;
      however, new technologies are needed to create and transplant these tissues. This
      study introduces a new connection between endoscopy and regenerative medicine in
      gastroenterology through specifically addressing how cell sheet technology can be
      a viable method of tissue creation and transplantation. 

PMID- 24679239
TI  - ESD around the world: Asia.
AB  - Endoscopic submucosal dissection (ESD) improves the quality of life of patients
      with early gastric cancer (EGC) and dysplasia by preserving gastric function. ESD
      in the treatment of EGC and dysplasia has become standard in Japan and Korea and
      is being developed and implemented in many major centers in Asia. With a well
      designed prospective study, long-term outcomes of expanded criteria for
      endoscopic resection of EGC are expected to provide reliable indications for
      endoscopic treatment. Ongoing and novel clinical investigations of minimally
      invasive approaches and close collaboration between Western and Asian countries
      are expected to establish the best way to treat EGC. 

PMID- 24679240
TI  - ESD around the world: Europe.
AB  - In Europe, endoscopic mucosal resection (EMR) is widely accepted as an
      appropriate diagnostic approach to obtain specimens for accurate histopathologic
      evaluation, which may change grading and local staging of early neoplasia
      determined by prior biopsies and imaging. In contrast to EMR, endoscopic
      submucosal dissection (ESD) allows resection of even large lesions in a single
      piece. Evidence on the clinical value of ESD is still limited and mainly based on
      data from Japan, and may not be directly applicable to Europe, where the outcome
      of ESD may be less favorable because of the limited Western expertise in this
      challenging technique. 

PMID- 24679241
TI  - ESD around the world: United States.
AB  - Endoscopic submucosal dissection (ESD) is a well-established advanced mucosal
      resection technique used in Japan, where it originated, and some other Asian
      countries. The technical difficulty and potentially higher rates of significant
      complications have been obstacles for its dissemination across the United States,
      on top of the lack of available equipment, candidate lesions in the
      gastrointestinal tract, and adequate training programs. Yet American physicians
      are becoming increasingly aware of the benefits of ESD. Simplification of
      technique, modification of tools and materials, and improved availability of
      training opportunities are essential in order to accelerate the adoption of ESD
      in the United States. 

PMID- 24679242
TI  - Endoscopic submucosal dissection: on the rise from East to West.

PMID- 24679243
TI  - Endoscopic submucosal dissection.

PMID- 24679244
TI  - Food allergen sensitization pattern in adults in relation to severity of atopic
      dermatitis.
AB  - BACKGROUND: Limited data are available on the frequency of IgE mediated food
      sensitization and food allergy (FA) in adults with atopic dermatitis (AD).
      OBJECTIVE: We investigated the pattern of food sensitization in adults with AD in
      relation to AD severity using multiplexed allergen microarray. METHODS: 211 adult
      patients referred between January 2010-July 2011 for evaluation of AD were
      unselectively included. Severity of AD was determined by therapy intensity,
      SASSAD-skin-score and sTARC levels. Allergen specific sIgE levels were measured
      by ImmunoCAP ISAC(r) microarray. FA was defined as convincing history taken by
      physician and sensitization to the corresponding allergen. RESULTS: Sensitization
      to food was found in 74.4% of the AD patients, 54% had a positive history of FA
      and 20.4% asymptomatic sensitization. There was no association between severity
      of AD and frequency of food sensitization or history of FA.Sensitization to PR-10
      related food allergens occurred most frequently (63.5%) and was independent from
      AD severity. Correspondingly, pollen-food syndrome accounted for most of the FA,
      being also independent from AD severity. Of all plant food allergens only
      sensitization to nAra h 1 was significantly more frequent in patients with severe
      AD. In the total group 75 (35.5%) patients with AD showed sensitization to any
      animal food allergen. The percentage was significantly higher in patients with
      severe AD (51.4%) compared to patients with mild/moderate AD (27.7%).
      Sensitization to cow's milk allergens, in particular to nBos d lactoferrin, was
      more frequent in severe AD patients. CONCLUSION: AD was frequently associated
      with food sensitization. The percentage of sensitization to animal food allergens
      was significantly higher in severe AD patients.

PMID- 24679245
TI  - Birds as potential reservoirs of tick-borne pathogens: first evidence of
      bacteraemia with Rickettsia helvetica.
AB  - BACKGROUND: Birds have long been known as carriers of ticks, but data from the
      literature are lacking on their role as a reservoir in the epidemiology of
      certain tick-borne disease-causing agents. Therefore, the aim of this study was
      to evaluate the presence of three emerging, zoonotic tick-borne pathogens in
      blood samples and ticks of birds and to assess the impact of feeding location
      preference and migration distance of bird species on their tick infestation.
      METHODS: Blood samples and ticks of birds were analysed with TaqMan real-time
      PCRs and conventional PCR followed by sequencing. RESULTS: During the spring and
      autumn bird migrations, 128 blood samples and 140 ticks (Ixodes ricinus,
      Haemaphysalis concinna and a Hyalomma specimen) were collected from birds
      belonging to 16 species. The prevalence of tick infestation and the presence of
      tick species were related to the feeding and migration habits of avian hosts.
      Birds were shown to be bacteraemic with Rickettsia helvetica and Anaplasma
      phagocytophilum, but not with Candidatus Neoehrlichia mikurensis. The prevalence
      of rickettsiae was high (51.4%) in ticks, suggesting that some of them may have
      acquired their infection from their avian host. CONCLUSION: Based on the present
      results birds are potential reservoirs of both I. ricinus transmitted zoonotic
      pathogens, R. helvetica and A. phagocytophilum, but their epidemiological role
      appears to be less important concerning the latter, at least in Central Europe.

PMID- 24679246
TI  - Clinical outcome after endoscopic therapy for occult vesicoureteral reflux in
      females: preliminary results of a retrospective case series.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical outcome after
      endoscopic therapy by injection of bulking agent in the treatment of occult
      vesicoureteral reflux (VUR) [no VUR on standard voiding cystourethrography
      (VCUG), but positive (99m)Tc-2,3-dimercaptosuccinic acid (DMSA) scan] in females
      who have recurrent febrile urinary tract infections (UTIs). MATERIAL AND METHODS:
      A case series was retrospectively identified of 24 females (mean age 15.5 years)
      with negative VCUG, but renal scars in one (n = 4) or both (n = 20) kidneys on
      DMSA scan. Endoscopic injection was performed bilaterally in 20 (83.3%) and
      unilaterally in four patients (16.7%). The incidence of postoperative UTIs was
      documented with a mean follow-up of 2.5 years (range 1-6 years). RESULTS: The
      mean renal part function (DMSA scan) on the left and right sides was 53.5% (15
      74%) and 47.3% (26-85%), respectively. Twenty-one out of 24 patients (87.5%)
      showed no evidence of any febrile UTIs postoperatively. One patient (4.2%)
      experienced a further febrile UTI 6 months after treatment. Two other patients
      (8.3%) had one questionable afebrile UTI, 4 and 3 years after therapy. Pressure
      flow electromyography confirmed a dysfunctional voiding pattern in 12 patients
      (50%) treated with pelvic floor therapy and behavioural interventions before
      endoscopic therapy. CONCLUSIONS: Injection of bulking agent seems to be a
      suitable treatment for occult VUR in females to prevent further febrile UTIs.
      Patients with occult VUR should undergo a careful evaluation of possible
      urodynamic disorders such as dysfunctional voiding. These findings should be
      studied in prospective trials before drawing any conclusions.

PMID- 24679247
TI  - Comparison of intermittent and continuous androgen deprivation and quality of
      life between patients with locally advanced and patients with metastatic prostate
      cancer: a post hoc analysis of the randomized FinnProstate Study VII.
AB  - OBJECTIVE: The aim of the study was to compare intermittent (IAD) and continuous
      (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and
      metastatic (M1) prostate cancer, and the effect of ADT on the quality of life.
      MATERIAL AND METHODS: In total, 852 men with advanced prostate cancer were
      enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose
      prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least
      50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT
      was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml
      or above baseline. RESULTS: Median follow-up time was 65 months. Median times
      from randomization to progression, death, prostate cancer death and treatment
      failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7,
      and 41.9 and 20.0 months, respectively (p < 0.001). No significant differences
      emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity
      limitation and social functioning in M1 patients, and a deleterious effect on
      physical capacity in M0 patients and on sexual functioning in both groups. IAD
      offered extra benefit for activity limitation, social functioning and recovery of
      sexual functioning. CONCLUSIONS: IAD is as efficient as CAD in treatment of
      locally advanced and metastatic prostate cancer. ADT improves quality of life in
      M1 patients, with IAD offering extra benefit.

PMID- 24679248
TI  - Ab initio thermodynamic model for magnesium carbonates and hydrates.
AB  - An ab initio thermodynamic framework for predicting properties of hydrated
      magnesium carbonate minerals has been developed using density-functional theory
      linked to macroscopic thermodynamics through the experimental chemical potentials
      for MgO, water, and CO2. Including semiempirical dispersion via the Grimme method
      and small corrections to the generalized gradient approximation of Perdew, Burke,
      and Ernzerhof for the heat of formation yields a model with quantitative
      agreement for the benchmark minerals brucite, magnesite, nesquehonite, and
      hydromagnesite. The model shows how small differences in experimental conditions
      determine whether nesquehonite, hydromagnesite, or magnesite is the result of
      laboratory synthesis from carbonation of brucite, and what transformations are
      expected to occur on geological time scales. Because of the reliance on parameter
      free first-principles methods, the model is reliably extensible to experimental
      conditions not readily accessible to experiment and to any mineral composition
      for which the structure is known or can be hypothesized, including structures
      containing defects, substitutions, or transitional structures during solid state
      transformations induced by temperature changes or processes such as water, CO2,
      or O2 diffusion. Demonstrated applications of the ab initio thermodynamic
      framework include an independent means to evaluate differences in thermodynamic
      data for lansfordite, predicting the properties of Mg analogues of Ca-based
      hydrated carbonates monohydrocalcite and ikaite, which have not been observed in
      nature, and an estimation of the thermodynamics of barringtonite from the
      stoichiometry and a single experimental observation. 

PMID- 24679249
TI  - Intrinsic debromination potential of polybrominated diphenyl ethers in different
      sediment slurries.
AB  - The fate of BDE-153 (BDE = brominated diphenyl ethers) in different mangrove,
      fresh water pond, and marine subsurface sediments collected from Hong Kong SAR
      was investigated. Under anaerobic conditions, all sediments showed good intrinsic
      abilities to reductively debrominate BDE-153, producing debromination products
      ranging from hexa- to mono-BDEs in 90 days. The half-lives of BDE-153 in eight
      different sediments varied from 7.6 to 165 days, with higher debromination in
      mangrove than marine and fresh water pond sediments. All sediments exhibited the
      preference in removing the bromine in para, followed by meta, and the lowest in
      ortho positions; however, fresh water pond sediments had relatively higher
      fractions of meta (BDE-99) and ortho substitution (BDE-118) of the three penta
      BDE products. Mai Po mangrove and fresh water pond subsurface sediments were also
      capable of debrominating BDE-47 in 90 days of anaerobic incubation with half
      lives of 76.2 and 56.9 days, respectively; but not BDE-209. BDE-47, -153, and 
      209 in Mai Po surface sediment were not transformed under 30 day aerobic
      incubation. This study demonstrated that the microbial-mediated debromination of
      BDE-47 and -153 occurred in natural subsurface sediments under anaerobic
      conditions although the rates and pathways varied among the sediment types. 

PMID- 24679250
TI  - Production and purification of recombinant enteropeptidase expressed in an insect
      baculovirus cell system.
AB  - Enteropeptidase (EC 3.4.21.9) is the glycoprotein enzyme in the small intestine
      that triggers the activation of the zymogens in pancreatic juice by converting
      trypsinogen into trypsin. Because of its physiological significance, there have
      been many studies on the expression, purification, and characterization of
      enteropeptidase from different species. The baculovirus expression system has
      been commonly used in research communities and scientific industries for the
      production of high levels of recombinant proteins, which require
      posttranslational modifications for functional activity. In the present study, we
      isolated bovine enteropeptidase catalytic subunit gene from Bos taurus indicus
      (GenBank accession no. KC756844), and cloned it in pFast Bac HT "A" baculovirus
      expression donor vector, under the polyhedrin promoter. Recombinant bovine
      enteropeptidase was expressed in SF-9 insect cells with high expression levels.
      Recombinant enteropeptidase was purified using Ni-NTA affinity chromatography. A
      6-mg quantity of pure active protein was obtained from 100 mL culture using this
      approach. Its activity and kinetic parameters were determined by cleavage of its
      fluorogenic substrate Gly-(Asp) 4-Lys-beta-naphthylamide. The recombinant bovine
      enteropeptidase showed a K m value of 0.75 +/- 0.02 mM with K cat 25 +/- 1 s. 

PMID- 24679251
TI  - Emerging frontiers in detection and control of bacterial biofilms.
AB  - Bacteria form surface-attached biofilm communities in nature. In contrast to free
      living cells, bacterial cells within biofilms resist sanitizers and
      antimicrobials. While building biofilms, cells physiologically adapt to sustain
      the otherwise lethal impacts of a variety of environmental stress conditions. In
      this development, the production and embedding of cells in extracellular
      polymeric substances plays a key role. Biofilm bacteria can cause a range of
      problems to food processing including reduced heat-cold transfer, clogging water
      pipelines, food spoilage and they may cause infections among consumers. Recent
      biofilm investigations with the aim of potential control approaches include a
      combination of bacterial genetics, systems biology, materials and mechanic
      engineering and chemical biology. 

PMID- 24679252
TI  - Genetic engineering of the chloroplast: novel tools and new applications.
AB  - The plastid genome represents an attractive target of genetic engineering in crop
      plants. Plastid transgenes often give high expression levels, can be stacked in
      operons and are largely excluded from pollen transmission. Recent research has
      greatly expanded our toolbox for plastid genome engineering and many new proof-of
      principle applications have highlighted the enormous potential of the
      transplastomic technology in both crop improvement and the development of plants
      as bioreactors for the sustainable and cost-effective production of
      biopharmaceuticals, enzymes and raw materials for the chemical industry. This
      review describes recent technological advances with plastid transformation in
      seed plants. It focuses on novel tools for plastid genome engineering and
      transgene expression and summarizes progress with harnessing the potential of
      plastid transformation in biotechnology. 

PMID- 24679253
TI  - Biotechnological solutions to the nitrogen problem.
AB  - The availability of nitrogen is one of the major limiting factors to crop growth.
      In the developed world, farmers use unsustainable levels of inorganic fertilisers
      to promote crop production. In contrast, in the developing world inorganic
      fertilisers are often not available and small-holder farmers suffer the resultant
      poor yields. Finding alternatives to inorganic fertilisers is critical for
      sustainable and secure food production. Bacteria and Archaea have evolved the
      capability to fix atmospheric nitrogen to ammonia, a form readily usable in
      biological processes. This capability presents an opportunity to improve the
      nutrition of crop plants, through the introduction into cereal crops of either
      the nitrogen fixing bacteria or the nitrogenase enzyme responsible for nitrogen
      fixation. While both approaches are challenging, recent advances have laid the
      groundwork to initiate these biotechnological solutions to the nitrogen problem. 

PMID- 24679254
TI  - Central role of cyclic electron transport around photosystem I in the regulation
      of photosynthesis.
AB  - Cyclic electron transport around photosystem I generates ATP without the
      accumulation of NADPH in chloroplasts. In angiosperms, electron transport
      consists of a PGR5-PGRL1 protein-dependent pathway and a chloroplast NADH
      dehydrogenase-like complex-dependent pathway. Most likely, the PGR5-PGRL1 pathway
      corresponds to the cyclic phosphorylation discovered by Arnon and contributes
      mainly to DeltapH formation in photosynthesis. ATP synthesis utilizes this
      DeltapH formed by both linear and PSI cyclic electron transport. Furthermore,
      acidification of the thylakoid lumen downregulates light energy utilization in
      photosystem II and also electron transport through the cytochrome b6f complex. In
      the absence of PGR5, chloroplast NDH compensates for the reduced DeltapH
      formation to some extent. Additionally, proton conductivity is upregulated,
      probably through ATPase, in pgr5 mutants. The photosynthetic machinery likely
      forms a complex network to maintain high photosynthesis activity under
      fluctuating light conditions. 

PMID- 24679255
TI  - Plant genome sequencing - applications for crop improvement.
AB  - It is over 10 years since the genome sequence of the first crop was published.
      Since then, the number of crop genomes sequenced each year has increased
      steadily. The amazing pace at which genome sequences are becoming available is
      largely due to the improvement in sequencing technologies both in terms of cost
      and speed. Modern sequencing technologies allow the sequencing of multiple
      cultivars of smaller crop genomes at a reasonable cost. Though many of the
      published genomes are considered incomplete, they nevertheless have proved a
      valuable tool to understand important crop traits such as fruit ripening, grain
      traits and flowering time adaptation. 

PMID- 24679256
TI  - Current topics in the biotechnological production of essential amino acids,
      functional amino acids, and dipeptides.
AB  - Amino acids play important roles in both human and animal nutrition and in the
      maintenance of health. Here, amino acids are classified into three groups: first,
      essential amino acids, which are essential to nutrition; second, functional amino
      acids, recently found to be important in the promotion of physiological
      functions; and third, dipeptides, which are used to resolve problematic features
      of specific free amino acids, such as their instability or insolubility. This
      review focusses on recent researches concerning the microbial production of
      essential amino acids (lysine and methionine), functional amino acids (histidine
      and ornithine), and a dipeptide (L-alanyl-L-glutamine).

PMID- 24679257
TI  - Environmental responses and phage susceptibility in foodborne pathogens:
      implications for improving applications in food safety.
AB  - Bacterial foodborne pathogens can rapidly respond to changes in their
      environment, granting them the ability to survive under a broad range of
      conditions. In doing so, they undergo physiological alterations that can
      influence the efficacy of detection and interventions used in the food industry.
      As bacteriophage-based applications in food safety are gaining traction, it is
      crucial that we consider the effect the environment can have on phage-host
      interactions. This review aims to bridge knowledge of the responses of bacterial
      foodborne pathogens to changing environmental conditions with our understanding
      of phage-host interactions. An improved understanding of these intersections will
      aid in the development of bacteriophage-based products for the detection,
      biocontrol and biosanitation of foodborne pathogens. 

PMID- 24679258
TI  - Renewable jet fuel.
AB  - Novel strategies for sustainable replacement of finite fossil fuels are intensely
      pursued in fundamental research, applied science and industry. In the case of jet
      fuels used in gas-turbine engine aircrafts, the production and use of synthetic
      bio-derived kerosenes are advancing rapidly. Microbial biotechnology could
      potentially also be used to complement the renewable production of jet fuel, as
      demonstrated by the production of bioethanol and biodiesel for piston engine
      vehicles. Engineered microbial biosynthesis of medium chain length alkanes, which
      constitute the major fraction of petroleum-based jet fuels, was recently
      demonstrated. Although efficiencies currently are far from that needed for
      commercial application, this discovery has spurred research towards future
      production platforms using both fermentative and direct photobiological routes. 

PMID- 24679259
TI  - Filamentous fungi are large-scale producers of pigments and colorants for the
      food industry.
AB  - With globalization in the research trends, healthier life styles, and the growing
      market for the natural food colorants in the economically fast-growing countries
      all over the world, filamentous fungi are being investigated as readily available
      sources of chemically diverse colorants. With two selected examples, polyketide
      Monascus-like pigments from the new fungal production strains, and the promising
      and yet unexplored hydroxy-anthraquinoid colorants, the present review highlights
      exciting recent findings, which may pave the way for alternative and/or
      additional biotechnological processes for the industrial production of natural
      food colorants of improved functionality. As an additional aspect, marine fungi
      are discussed as potential sources of novel pigments of numerous color hues and
      atypical chemical structures. 

PMID- 24679260
TI  - Novel perspectives for the engineering of abiotic stress tolerance in plants.
AB  - Adverse environmental conditions pose serious limitations to agricultural
      production. Classical biotechnological approaches towards increasing abiotic
      stress tolerance focus on boosting plant endogenous defence mechanisms. However,
      overexpression of regulatory elements or effectors is usually accompanied by
      growth handicap and yield penalties due to crosstalk between developmental and
      stress-response networks. Herein we offer an overview on novel strategies with
      the potential to overcome these limitations based on the engineering of
      regulatory systems involved in the fine-tuning of the plant response to
      environmental hardships, including post-translational modifications, small RNAs,
      epigenetic control of gene expression and hormonal networks. The development and
      application of plant synthetic biology tools and approaches will add new
      functionalities and perspectives to genetic engineering programs for enhancing
      abiotic stress tolerance. 

PMID- 24679261
TI  - Microbial production of antioxidant food ingredients via metabolic engineering.
AB  - Antioxidants are biological molecules with the ability to protect vital
      metabolites from harmful oxidation. Due to this fascinating role, their
      beneficial effects on human health are of paramount importance. Traditional
      approaches using solvent-based extraction from food/non-food sources and chemical
      synthesis are often expensive, exhaustive, and detrimental to the environment.
      With the advent of metabolic engineering tools, the successful reconstitution of
      heterologous pathways in Escherichia coli and other microorganisms provides a
      more exciting and amenable alternative to meet the increasing demand of natural
      antioxidants. In this review, we elucidate the recent progress in metabolic
      engineering efforts for the microbial production of antioxidant food ingredients 
      polyphenols, carotenoids, and antioxidant vitamins.

PMID- 24679262
TI  - Plant cell wall engineering: applications in biofuel production and improved
      human health.
AB  - Plant cell walls consist largely of cellulose, non-cellulosic polysaccharides and
      lignin. Concerted attempts are underway to convert wall polysaccharides from crop
      plant residues into renewable transport fuels and other valuable products, and to
      exploit the dietary benefits of cereal grain wall polysaccharides in human
      health. Attempts to improve plant performance for these applications have
      involved the manipulation of the levels and structures of wall components. Some
      successes in altering non-cellulosic polysaccharides has been achieved, but it
      would appear that drastic changes in cellulose are more difficult to engineer.
      Nevertheless, future prospects for both genetically modified (GM) and non-GM
      technologies to modify plant cell wall composition and structure remain bright,
      and will undoubtedly find applications beyond the current focus on human health
      and biofuel production. 

PMID- 24679264
TI  - Gene clustering in plant specialized metabolism.
AB  - Physically linked clusters of genes that encode the enzymatic information for the
      synthesis of specialized metabolites are a well-established feature of microbial
      secondary metabolism. In contrast, the biosynthesis of plant specialized
      metabolites has until recently been thought to be almost exclusively encoded by
      genes that are randomly scattered in the genome. However, recent reports
      highlight the growing number of examples of gene clusters for specialized
      metabolic pathways in plants. Numerous gene clusters that encode for the
      biosynthesis of different classes of metabolite have now been discovered in a
      variety of plant species. Comparison of these characterized clusters now enables
      us to begin to define their salient features and to exploit plant biosynthetic
      gene clusters for synthetic biology applications. 

PMID- 24679263
TI  - Rational identification of diet-derived postbiotics for improving intestinal
      microbiota function.
AB  - The intestinal microbiota plays an important role in a wide range of functions
      and whole body homeostasis. Recent advances have linked microbiota dysbiosis to
      conditions ranging from Crohn's disease to cancer. The restoration or
      strengthening of the intestinal microbiota through diet-based approaches such as
      probiotics and prebiotics has been proposed for combating the onset or
      progression of these diseases. In this review, we highlight the importance of
      postbiotics for the manipulation of the intestinal microbiota, with special
      emphasis on systems biology computational tools and targeted metabolomics for the
      rational discovery and identification of these bioactive molecules. The
      identification of novel postbiotics and the pathways responsible for their
      production should lead to improved mechanistic understanding of the role that
      specific probiotics, prebiotics, and postbiotics have in restoring intestinal
      microbiota composition and function. 

PMID- 24679265
TI  - Xylan biosynthesis.
AB  - Plant cells are surrounded by a rigid wall made up of cellulose microfibrils,
      pectins, hemicelluloses, and lignin. This cell wall provides structure and
      protection for plant cells. In grasses and in dicot secondary cell walls, the
      major hemicellulose is a polymer of beta-(1,4)-linked xylose units called xylan.
      Unlike cellulose--which is synthesized by large complexes at the plasma membrane-
      xylan is synthesized by enzymes in the Golgi apparatus. Xylan synthesis thus
      requires the coordinated action and regulation of these synthetic enzymes as well
      as others that synthesize and transport substrates into the Golgi. Recent
      research has identified several genes involved in xylan synthesis, some of which
      have already been used in engineering efforts to create plants that are better
      suited for biofuel production.

PMID- 24679266
TI  - Are designer plant cell walls a realistic aspiration or will the plasticity of
      the plant's metabolism win out?
AB  - Plants have been redesigned by humans since the advent of modern agriculture some
      10000 years ago, to provide ever increasing benefits to society. The phenomenal
      success of the green revolution in converting biomass from vegetative tissues
      into grain yield has sustained a growing population. At the dawn of the 21st
      century the need to further optimise plant biomass (largely plant walls) for a
      sustainable future is increasingly evident as our supply of fossil fuels is
      finite and the quality of our crop-based foods (functional foods; also determined
      by the composition of walls) are critical to maintaining a healthy lifestyle. Our
      capacity to engineer 'designer walls' suited to particular purposes is
      challenging plant breeders and biotechnologists in unprecedented ways. In this
      review we provide an overview of the critical steps in the assembly and
      remodelling of walls, the success (or otherwise) of such approaches and highlight
      another complex network, the cell surface, as a cell wall integrity (CWI) sensor
      that exerts control over wall composition and will need to be considered in any
      future modification of walls for agro-industrial purposes. 

PMID- 24679267
TI  - Salt resistant crop plants.
AB  - Soil salinity is a major constraint to agriculture. To improve salinity tolerance
      of crops, various traits can be incorporated, including ion exclusion, osmotic
      tolerance and tissue tolerance. We review the roles of a range of genes involved
      in salt tolerance traits. Different tissues and cells are adapted for specific
      and often diverse function, so it is important to express the genes in specific
      cell-types and to pyramid a range of traits. Modern biotechnology (marker
      assisted selection or genetic engineering) needs to be increasingly used to
      introduce the correct combination of genes into elite crop cultivars.
      Importantly, the effects of introduced genes need to be evaluated in the field to
      determine their effect on salinity tolerance and yield improvement. 

PMID- 24679268
TI  - Promoting epithelium regeneration for esophageal tissue engineering through
      basement membrane reconstitution.
AB  - Scaffolds mimicking hierarchical features of native extracellular matrices may
      facilitate cell growth and anatomical tissue regeneration. In our previous study,
      esophageal basement membrane (BM) was shown to be composed of interwoven fibers
      with mean diameter of 66 +/- 24 nm (range 28-165 nm) and with abundant pores of
      unequal sizes. The main extracellular matrix (ECM) contents found in porcine
      esophageal BM were collagen IV, laminin, entactin, and proteoglycans. In this
      work, biodegradable polycaprolactone (PCL) and silk fibroin (SF) were spun with
      electrospinning technology, both individually and in combination, to fabricate
      fibrous scaffolds with diameters between 64 and 200 nm. The surface morphologies
      of PCL, PCL/SF, and SF scaffolds were observed under scanning electron
      microscopy. Their mechanical properties were tested and the cytocompatibility was
      evaluated in vitro via culture of primary epithelial cells (ECs). The SF or
      PCL/SF scaffold favorably promoted epithelial cell attachment and proliferation
      comparing with PCL scaffold. However, mitochondrial activity of epithelial cells
      was greatly promoted when major BM proteins were coated onto the electrospun
      scaffold to provide an ECM-like structure. Results from in vivo tests revealed
      that the electrospun scaffolds coated with BM protein possess good
      biocompatibility and capability to promote epithelium regeneration. 

PMID- 24679269
TI  - Improved survival rate by temperature control at compression sites in rat model
      of crush syndrome.
AB  - BACKGROUND: Crush syndrome (CS) has been reported in disasters, terrorist
      incidents, and accidents, and the clinical and pathologic picture has gradually
      been clarified. Few lethal and reproducible animal models of CS with use of a
      quantitative load are available. A new model is needed to investigate pathologic
      and therapeutic aspects of this injury. MATERIALS AND METHODS: Using a device
      built from commercially available components, both hindlimbs of anesthetized rats
      were respectively compressed for 6 h using 3.6-kg blocks. The effects of trunk
      warming alone without compressed hindlimbs (Group A), non-warming at room
      temperature (Group B), whole-body warming including compressed hindlimbs (Group
      C), or warming of compressed hindlimbs alone (Group D) during compression were
      examined. Survival rates were compared and hematological and histologic analyses
      were performed at specific time points after compression release. RESULTS: Limb
      or whole-body warming significantly worsened the survival of rats. We found a
      much lower survival rate of 0%-10% in animals, in which the hindlimbs were warmed
      during compression (Groups C and D) at 12 h after compression release, compared
      with 90%-100% in animals without warming of the hindlimbs (Groups A and B).
      Groups C and D showed significantly enhanced hyperkalemia at >=4 h after
      compression release and all blood samples from dead cases showed hyperkalemia
      (>10 mEq/L). CONCLUSIONS: We developed a new lethal and reproducible rat CS model
      with a quantitative load. This study found that warming of compressed limbs
      worsened the survival rate and significantly enhanced hyperkalemia, apparently
      leading to cardiac arrest.

PMID- 24679270
TI  - Fundamental monogamy relation between contextuality and nonlocality.
AB  - We show that the no-disturbance principle imposes a tradeoff between locally
      contextual correlations violating the Klyachko-Can-Binicioglu-Shumovski
      inequality and spatially separated correlations violating the Clauser-Horne
      Shimony-Holt inequality. The violation of one inequality forbids the violation of
      the other. We also obtain the corresponding monogamy relation imposed by quantum
      theory for a qutrit-qubit system. Our results show the existence of fundamental
      monogamy relations between contextuality and nonlocality that suggest that
      entanglement might be a particular form of a more fundamental resource. 

PMID- 24679271
TI  - Can observed randomness be certified to be fully intrinsic?
AB  - In general, any observed random process includes two qualitatively different
      forms of randomness: apparent randomness, which results both from ignorance or
      lack of control of degrees of freedom in the system, and intrinsic randomness,
      which is not ascribable to any such cause. While classical systems only possess
      the first kind of randomness, quantum systems may exhibit some intrinsic
      randomness. In this Letter, we provide quantum processes in which all the
      observed randomness is fully intrinsic. These results are derived under minimal
      assumptions: the validity of the no-signaling principle and an arbitrary (but not
      absolute) lack of freedom of choice. Our results prove that quantum predictions
      cannot be completed already in simple finite scenarios, for instance of three
      parties performing two dichotomic measurements. Moreover, the observed randomness
      tends to a perfect random bit when increasing the number of parties, thus,
      defining an explicit process attaining full randomness amplification. 

PMID- 24679272
TI  - Experimental violation of multipartite Bell inequalities with trapped ions.
AB  - We report on the experimental violation of multipartite Bell inequalities by
      entangled states of trapped ions. First, we consider resource states for
      measurement-based quantum computation of between 3 and 7 ions and show that all
      strongly violate a Bell-type inequality for graph states, where the criterion for
      violation is a sufficiently high fidelity. Second, we analyze Greenberger-Horne
      Zeilinger states of up to 14 ions generated in a previous experiment using
      stronger Mermin-Klyshko inequalities, and show that in this case the violation of
      local realism increases exponentially with system size. These experiments
      represent a violation of multipartite Bell-type inequalities of deterministically
      prepared entangled states. In addition, the detection loophole is closed. 

PMID- 24679273
TI  - Local observation of pair condensation in a Fermi gas at unitarity.
AB  - We present measurements of the local (homogeneous) density-density response
      function of a Fermi gas at unitarity using spatially resolved Bragg spectroscopy.
      By analyzing the Bragg response across one axis of the cloud, we extract the
      response function for a uniform gas which shows a clear signature of the Bose
      Einstein condensation of pairs of fermions when the local temperature drops below
      the superfluid transition temperature. The method we use for local measurement
      generalizes a scheme for obtaining the local pressure in a harmonically trapped
      cloud from the line density and can be adapted to provide any homogeneous
      parameter satisfying the local density approximation. 

PMID- 24679274
TI  - One-dimensional transport of bosons between weakly linked reservoirs.
AB  - We study a flow of ultracold bosonic atoms through a one-dimensional channel that
      connects two macroscopic three-dimensional reservoirs of Bose-condensed atoms via
      weak links implemented as potential barriers between each of the reservoirs and
      the channel. We consider reservoirs at equal chemical potentials so that a
      superflow of the quasicondensate through the channel is driven purely by a phase
      difference 2Phi imprinted between the reservoirs. We find that the superflow
      never has the standard Josephson form ~sin2Phi. Instead, the superflow
      discontinuously flips direction at 2Phi=+/-pi and has metastable branches. We
      show that these features are robust and not smeared by fluctuations or phase
      slips. We describe a possible experimental setup for observing these phenomena. 

PMID- 24679275
TI  - Derivation of hydrodynamics from the Hamiltonian description of particle systems.
AB  - Hamiltonian particle systems may exhibit nonlinear hydrodynamic phenomena as the
      time evolution of the density fields of energy, momentum, and mass. In this
      Letter, an exact equation describing the time evolution is derived assuming the
      local Gibbs distribution at initial time. The key concept in the derivation is an
      identity similar to the fluctuation theorems. The Navier-Stokes equation is
      obtained as a result of simple perturbation expansions in a small parameter that
      represents the scale separation. 

PMID- 24679276
TI  - Systematic parameter errors in inspiraling neutron star binaries.
AB  - The coalescence of two neutron stars is an important gravitational wave source
      for LIGO and other detectors. Numerous studies have considered the precision with
      which binary parameters (masses, spins, Love numbers) can be measured. Here I
      consider the accuracy with which these parameters can be determined in the
      presence of systematic errors due to waveform approximations. These
      approximations include truncation of the post-Newtonian (PN) series and neglect
      of neutron star (NS) spin, tidal deformation, or orbital eccentricity. All of
      these effects can yield systematic errors that exceed statistical errors for
      plausible parameter values. In particular, neglecting spin, eccentricity, or high
      order PN terms causes a significant bias in the NS Love number. Tidal effects
      will not be measurable with PN inspiral waveforms if these systematic errors are
      not controlled. 

PMID- 24679277
TI  - Upper limit on a stochastic background of gravitational waves from seismic
      measurements in the range 0.05-1 Hz.
AB  - In this Letter, we present an upper limit of OmegaGW<1.2*108 on an isotropic
      stochastic gravitational-wave (GW) background integrated over a year in the
      frequency range 0.05-1 Hz, which improves current upper limits from high
      precision laboratory experiments by about 9 orders of magnitude. The limit is
      obtained using the response of Earth itself to GWs via a free-surface effect
      described more than 40 years ago by Dyson. The response was measured by a global
      network of broadband seismometers selected to maximize the sensitivity.

PMID- 24679278
TI  - Hypercharged dark matter and direct detection as a probe of reheating.
AB  - The lack of new physics at the LHC so far weakens the argument for TeV scale
      thermal dark matter. On the other hand, heavier, nonthermal dark matter is
      generally difficult to test experimentally. Here we consider the interesting and
      generic case of hypercharged dark matter, which can allow for heavy dark matter
      masses without spoiling testability. Planned direct detection experiments will be
      able to see a signal for masses up to an incredible 1010  GeV, and this can
      further serve to probe the reheating temperature up to about 109  GeV, as
      determined by the nonthermal dark matter relic abundance. The Z-mediated nature
      of the dark matter scattering may be determined in principle by comparing
      scattering rates on different detector nuclei, which in turn can reveal the dark
      matter mass. We will discuss the extent to which future experiments may be able
      to make such a determination. 

PMID- 24679279
TI  - B(s,d)->l(+)l(-) in the standard model with reduced theoretical uncertainty.
AB  - We combine our new results for the O(alphaem) and O(alphas2) corrections to Bs,d
      >l+l-, and present updated branching ratio predictions for these decays in the
      standard model. Inclusion of the new corrections removes major theoretical
      uncertainties of perturbative origin that have just begun to dominate over the
      parametric ones. For the recently observed muonic decay of the Bs meson, our
      calculation gives B-(Bs->MU+MU-)=(3.65+/-0.23)*10-9. 

PMID- 24679280
TI  - Production of hhjj at the LHC.
AB  - Until now, a phenomenologically complete analysis of the hh+2j channel at the LHC
      has been missing. This is mostly due to the high complexity of the involved one
      loop gluon fusion contribution and the fact that a reliable estimate thereof
      cannot be obtained through simplified calculations in the mt->infinity limit. In
      this Letter, we report on the LHC's potential to access di-Higgs production in
      association with two jets in a fully showered hadron-level analysis. Our study
      includes the finite top and bottom mass dependencies for the gluon fusion
      contribution. 

PMID- 24679281
TI  - Next-to-leading order QCD factorization for semi-inclusive deep inelastic
      scattering at twist 4.
AB  - Within the framework of a high-twist approach, we calculate the next-to-leading
      order (NLO) perturbative QCD corrections to the transverse momentum broadening in
      semi-inclusive hadron production in deeply inelastic e+A collisions, as well as
      lepton pair production in p+A collisions. With explicit calculations of both real
      and virtual contributions, we verify, for the first time, the factorization
      theorem at twist 4 in NLO for the nuclear-enhanced transverse momentum weighted
      differential cross section and demonstrate the universality of the associated
      twist-4 quark-gluon correlation function. We also identify the QCD evolution
      equation for the twist-4 quark-gluon correlation function in a large nucleus,
      which can be solved to determine the scale dependence of the jet transport
      parameter in the study of jet quenching. 

PMID- 24679282
TI  - Universality and the QCD Anderson transition.
AB  - We study the Anderson-type transition previously found in the spectrum of the QCD
      quark Dirac operator in the high-temperature, quark-gluon plasma phase. Using
      finite size scaling for the unfolded level spacing distribution, we show that in
      the thermodynamic limit there is a genuine mobility edge, where the spectral
      statistics changes from Poisson to Wigner-Dyson statistics in a nonanalytic way.
      We determine the correlation length critical exponent nu and find that it is
      compatible with that of the unitary Anderson model. 

PMID- 24679283
TI  - Ab initio calculation of the spectrum and structure of (16)O.
AB  - We present ab initio lattice calculations of the low-energy even-parity states of
      16O using chiral nuclear effective field theory. We find good agreement with the
      empirical energy spectrum, and with the electromagnetic properties and transition
      rates. For the ground state, we find that the nucleons are arranged in a
      tetrahedral configuration of alpha clusters. For the first excited spin-0 state,
      we find that the predominant structure is a square configuration of alpha
      clusters, with rotational excitations that include the first spin-2 state.

PMID- 24679284
TI  - beta decay of (38)Ca: sensitive test of isospin symmetry-breaking corrections
      from mirror superallowed 0+ -> 0+ transitions.
AB  - We report the first branching-ratio measurement of the superallowed 0+->0+beta
      transition from Ca38. The result, 0.7728(16), leads to an ft value of 3062.3(68)
      s with a relative precision of +/-0.2%. This makes possible a high-precision
      comparison of the ft values for the mirror superallowed transitions, Ca38->38mK
      and K38m->Ar38, which sensitively tests the isospin symmetry-breaking corrections
      required to extract Vud, the up-down quark-mixing element of the Cabibbo
      Kobayashi-Maskawa (CKM) matrix, from superallowed beta decay. The result supports
      the corrections currently used and points the way to even tighter constraints on
      CKM unitarity. 

PMID- 24679285
TI  - Extracting phase and amplitude modifications of laser-coupled Fano resonances.
AB  - Fano line shapes observed in absorption spectra encode information on the
      amplitude and phase of the optical dipole response. A change in the Fano line
      shape, e.g., by interaction with short-pulsed laser fields, allows us to extract
      dynamical modifications of the amplitude and phase of the coupled excited quantum
      states. We introduce and apply this physical mechanism to near-resonantly coupled
      doubly excited states in helium. This general approach provides a physical
      understanding of the laser-induced spectral shift of absorption-line maxima on a
      sub-laser-cycle time scale as they are ubiquitously observed in attosecond
      transient-absorption measurements. 

PMID- 24679286
TI  - Terahertz-induced field-free orientation of rotationally excited molecules.
AB  - We have used picosecond THz pulses to induce transient field-free orientation of
      OCS molecules. Coherent optical Raman excitation prepares the molecules in
      rotational superposition states prior to THz irradiation, substantially enhancing
      the degree of orientation. The time-dependent alignment and orientation are
      characterized via Coulomb explosion in an intense probe laser. The degree of OCS
      orientation is an order of magnitude larger than previously observed following
      THz irradiation and is achieved with a significantly smaller THz field.The field
      free orientation level is comparable to that generated using pulsed, two-color
      laser fields but is obtained with negligible target ionization. 

PMID- 24679287
TI  - malpha(7)-order corrections in the hydrogen molecular ions and antiprotonic
      helium.
AB  - We present a calculation of the complete set of QED corrections of order malpha7
      for one-electron two-center systems. Leading corrections of order malpha8 are
      also considered, which allows us to estimate the magnitude of yet uncalculated
      contributions. The theoretical uncertainty on the frequencies of rovibrational
      transitions in the hydrogen molecular ions H2+ and HD+, and of two-photon
      transition in antiprotonic helium is reduced by about 1 order of magnitude, down
      to (3-4)*10-11 and 10-10, respectively. These results open new perspectives for
      improved determination of the proton- and antiproton-to-electron mass ratios by
      precision spectroscopy experiments. 

PMID- 24679288
TI  - Three-body interacting bosons in free space.
AB  - We propose a method of controlling two- and three-body interactions in an
      ultracold Bose gas in any dimension. The method requires us to have two coupled
      internal single-particle states split in energy such that the upper state is
      occupied virtually but amply during collisions. By varying system parameters, one
      can switch off the two-body interaction while maintaining a strong three-body
      one. The mechanism can be implemented for dipolar bosons in the bilayer
      configuration with tunneling or in an atomic system by using radio-frequency
      fields to couple two hyperfine states. One can then aim to observe a purely three
      body interacting gas, dilute self-trapped droplets, the paired superfluid phase,
      Pfaffian state, and other exotic phenomena. 

PMID- 24679289
TI  - Relativistic transfer ionization and the Breit interaction.
AB  - We consider correlated transfer ionization in relativistic collisions between a
      highly charged ion and a light atom. In this process two quasifree electrons of
      the atom interact with each other during the short collision time that results in
      the capture of one of them by the ion and emission of the other. We show that
      this process is strongly influenced by the generalized Breit interaction already
      at modest relativistic impact energies. 

PMID- 24679290
TI  - Electronic friction dominates hydrogen hot-atom relaxation on Pd(100).
AB  - We study the dynamics of transient hot H atoms on Pd(100) that originated from
      dissociative adsorption of H2. The methodology developed here, denoted AIMDEF,
      consists of ab initio molecular dynamics simulations that include a friction
      force to account for the energy transfer to the electronic system. We find that
      the excitation of electron-hole pairs is the main channel for energy dissipation,
      which happens at a rate that is five times faster than energy transfer into Pd
      lattice motion. Our results show that electronic excitations may constitute the
      dominant dissipation channel in the relaxation of hot atoms on surfaces. 

PMID- 24679291
TI  - Spin squeezing in a Rydberg lattice clock.
AB  - We theoretically demonstrate a viable approach to spin squeezing in optical
      lattice clocks via optical dressing of one clock state to a highly excited
      Rydberg state, generating switchable atomic interactions. For realistic
      experimental parameters, these interactions are shown to generate over 10 dB of
      squeezing in large ensembles within a few microseconds and without degrading the
      subsequent clock interrogation. 

PMID- 24679292
TI  - Entangling different-color photons via time-resolved measurement and active feed
      forward.
AB  - Entangling independent photons is not only of fundamental interest but also of
      crucial importance for quantum-information science. Two-photon interference is a
      major method for entangling independent identical photons. If two photons are
      different in color, perfect two-photon coalescence can no longer happen, which
      makes the entangling of different-color photons difficult to realize. In this
      Letter, by exploring and developing time-resolved measurement and active feed
      forward, we have entangled two independent photons of different colors for the
      first time. We find that entanglement with a varying form can be identified for
      different two-photon temporal modes through time-resolved measurement. By using
      active feed forward, we are able to convert the varying entanglement into uniform
      entanglement. Adopting these measures, we have successfully entangled two photons
      with a frequency separation 16 times larger than their linewidths. In addition to
      its fundamental interest, our work also provides an approach for solving the
      frequency-mismatch problem for future quantum networks. 

PMID- 24679293
TI  - Nonlinear mode coupling and synchronization of a vacuum-trapped nanoparticle.
AB  - We study the dynamics of a laser-trapped nanoparticle in high vacuum. Using
      parametric coupling to an external excitation source, the linewidth of the
      nanoparticle's oscillation can be reduced by three orders of magnitude. We show
      that the oscillation of the nanoparticle and the excitation source are
      synchronized, exhibiting a well-defined phase relationship. Furthermore, the
      external source can be used to controllably drive the nanoparticle into the
      nonlinear regime, thereby generating strong coupling between the different
      translational modes of the nanoparticle. Our work contributes to the
      understanding of the nonlinear dynamics of levitated nanoparticles in high vacuum
      and paves the way for studies of pattern formation, chaos, and stochastic
      resonance. 

PMID- 24679294
TI  - Supersensitive polarization microscopy using NOON states of light.
AB  - A quantum polarized light microscope using entangled NOON states with N=2 and N=3
      is shown to provide phase supersensitivity beyond the standard quantum limit. We
      constructed such a microscope and imaged birefringent objects at a very low light
      level of 50 photons per pixel, where shot noise seriously hampers classical
      imaging. The NOON light source is formed by combining a coherent state with
      parametric down-converted light. We were able to show improved phase images with
      sensitivity close to the Heisenberg limit. 

PMID- 24679295
TI  - Front pinning and localized states analogues in long-delayed bistable systems.
AB  - Localized structures have been observed in many spatially extended systems of
      either biological, chemical, or physical nature. Here, we study experimentally
      front pinning and dissipative localized structures in a delayed optical system
      based on a bistable semiconductor laser with optoelectronic feedback. We observe
      that many of the concepts known to apply to spatially localized structures also
      apply in this context, with specificities related to the lack of reversibility
      symmetry. Numerical simulations based on purely prototypical modeling reproduce
      very well the experimental findings, which indicates that the results do not
      depend on the specific physical system under consideration, but are, on the
      contrary, very generic features of time delayed systems. 

PMID- 24679296
TI  - Cavity-enhanced high-harmonic generation with spatially tailored driving fields.
AB  - We theoretically and experimentally investigate high-harmonic generation in a 78
      MHz enhancement cavity with a transverse mode having on-axis intensity maxima at
      the focus and minima at an opening in the following mirror. We find that the
      conversion efficiency is comparable to that achievable with a Gaussian mode,
      whereas the output coupling efficiency can be significantly improved over any
      other demonstrated technique. This approach offers additional power scaling
      advantages and additional degrees of freedom in shaping the harmonic emission,
      paving the way to high-power extreme-ultraviolet frequency combs and the
      generation of multi-MHz repetition-rate-isolated attosecond pulses. 

PMID- 24679297
TI  - Taylor particle dispersion during transition to fully developed two-dimensional
      turbulence.
AB  - We report new measurements of single particle dispersion in turbulent two
      dimensional (2D) flows. Laboratory experiments in electromagnetically driven and
      Faraday wave driven turbulence reveal a transition from weakly dispersing
      superdiffusive regime to strongly dispersing Brownian diffusion as the flow
      energy is increased in a broad range. The transition to fully developed 2D
      turbulence is characterized by the topological changes in the fluid particle
      trajectories and the development of self-similar diffusion. The degree of 2D
      turbulence development can be quantified by a parameter describing the deviation
      of single particle dispersion from the Taylor dispersion. 

PMID- 24679298
TI  - Virtual seafloor reduces internal wave generation by tidal flow.
AB  - Our numerical simulations of tidal flow of a stratified fluid over periodic knife
      edge ridges and random topography reveal that the time-averaged tidal energy
      converted into internal gravity wave radiation arises only from the section of a
      ridge above a virtual seafloor. The average radiated power is approximated by the
      power predicted by linear theory if the height of the ridge is measured relative
      to the virtual floor. The concept of a virtual floor can extend the applicability
      of linear theory to global predictions of the conversion of tidal energy into
      internal wave energy in the oceans. 

PMID- 24679299
TI  - Electrostatic ion cyclotron and ion plasma waves in a symmetric pair-ion plasma
      cylinder.
AB  - Complicated wave behavior observed in the cylindrical pair-ion (fullerene)
      experiments by Oohara and co-workers are now identified to be low harmonic ion
      cyclotron waves combined with ion plasma oscillations inherent to kinetic theory.
      The electrostatic dispersion equation derived is based on an approximation for
      the current from the exact solutions of the characteristic cylindrical geometry
      form of the Vlasov plasma equation in a uniform magnetized plasma cylinder
      surrounded by a larger metal boundary outside a vacuum gap, which thus differs
      from that in unbounded plasmas. Positive and negative ions, differing only in the
      sign of their charge, respond to a potential in the same time scale and cooperate
      to reflect the enhanced kinetic orbital behaviors to the macroscopic propagation
      characteristics. In addition, the experimental value of the Larmor radius
      (comparable to the discharge radius but small enough to make the analytic
      approximation useful) makes higher harmonic ion cyclotron effects both observable
      and calculable with the appropriate approximation for the kinetic theory. 

PMID- 24679301
TI  - Novel characterization of capsule x-ray drive at the National Ignition Facility.
AB  - Indirect drive experiments at the National Ignition Facility are designed to
      achieve fusion by imploding a fuel capsule with x rays from a laser-driven
      hohlraum. Previous experiments have been unable to determine whether a deficit in
      measured ablator implosion velocity relative to simulations is due to inadequate
      models of the hohlraum or ablator physics. ViewFactor experiments allow for the
      first time a direct measure of the x-ray drive from the capsule point of view.
      The experiments show a 15%-25% deficit relative to simulations and thus explain
      nearly all of the disagreement with the velocity data. In addition, the data from
      this open geometry provide much greater constraints on a predictive model of
      laser-driven hohlraum performance than the nominal ignition target. 

PMID- 24679300
TI  - Resolving ultrafast heating of dense cryogenic hydrogen.
AB  - We report on the dynamics of ultrafast heating in cryogenic hydrogen initiated by
      a ?300  fs, 92 eV free electron laser x-ray burst. The rise of the x-ray
      scattering amplitude from a second x-ray pulse probes the transition from dense
      cryogenic molecular hydrogen to a nearly uncorrelated plasmalike structure,
      indicating an electron-ion equilibration time of ~0.9  ps. The rise time agrees
      with radiation hydrodynamics simulations based on a conductivity model for
      partially ionized plasma that is validated by two-temperature density-functional
      theory. 

PMID- 24679302
TI  - Magnetic reconnection in plasma under inertial confinement fusion conditions
      driven by heat flux effects in Ohm's law.
AB  - In the interaction of high-power laser beams with solid density plasma there are
      a number of mechanisms that generate strong magnetic fields. Such fields
      subsequently inhibit or redirect electron flows, but can themselves be advected
      by heat fluxes, resulting in complex interplay between thermal transport and
      magnetic fields. We show that for heating by multiple laser spots reconnection of
      magnetic field lines can occur, mediated by these heat fluxes, using a fully
      implicit 2D Vlasov-Fokker-Planck code. Under such conditions, the reconnection
      rate is dictated by heat flows rather than Alfvenic flows. We find that this
      mechanism is only relevant in a high beta plasma. However, the Hall parameter
      omegactauei can be large so that thermal transport is strongly modified by these
      magnetic fields, which can impact longer time scale temperature homogeneity and
      ion dynamics in the system. 

PMID- 24679303
TI  - Microscopic origin and universality classes of the Efimov three-body parameter.
AB  - The low-energy spectrum of three particles interacting via nearly resonant two
      body interactions in the Efimov regime is set by the so-called three-body
      parameter. We show that the three-body parameter is essentially determined by the
      zero-energy two-body correlation. As a result, we identify two classes of two
      body interactions for which the three-body parameter has a universal value in
      units of their effective range. One class involves the universality of the three
      body parameter recently found in ultracold atom systems. The other is relevant to
      short-range interactions that can be found in nuclear physics and solid-state
      physics. 

PMID- 24679304
TI  - Entropically stabilized dislocations.
AB  - Dislocations are line defects that play a key role in the plasticity of
      crystalline materials and affect their thermal, chemical, and electrical
      properties. Typically dislocations are treated as stable defects; e.g., the
      equilibrium core structure of a dislocation is obtained by minimizing the crystal
      potential energy with respect to atom positions. Here we show for the first time
      the possibility of "entropically stabilized dislocations" that exist due to
      entropic effects without a corresponding potential energy well. An entropically
      stabilized dislocation was discovered in an accelerated multiscale quasicontinuum
      simulation. Its entropic nature was verified with fully atomistic free energy
      calculations and explained by a simple continuum-based model. This result has
      important consequences for the study of dislocations as well as for temporal
      multiscale methods that use information from the potential energy surface to
      accelerate time in molecular simulations. 

PMID- 24679305
TI  - Scaling theory of two-phase dendritic growth in undercooled ternary melts.
AB  - Two-phase dendrites are needlelike crystals with a eutectic internal structure
      growing during solidification of ternary alloys. We present a scaling theory of
      these objects based on Ivantsov's theory of dendritic growth and the Jackson-Hunt
      theory of eutectic growth. The additional introduction of the relationship
      rho~lambda (rho: dendrite tip radius; lambda: eutectic interphase spacing)
      suggested by recent experimental results [S. Akamatsu et al., Phys. Rev. Lett.
      104, 056101 (2010)] leads to a complete solution of theselection problem and to
      the scaling rule rho~lambda -1/2 (v: dendrite tip growth rate).

PMID- 24679306
TI  - Soft modes and nonaffine rearrangements in the inherent structures of supercooled
      liquids.
AB  - We find that the hierarchical organization of the potential energy landscape in a
      model supercooled liquid can be related to a change in the spatial distribution
      of soft normal modes. For groups of nearby minima, between which fast relaxation
      processes typically occur, the localization of the soft modes is very similar.
      The spatial distribution of soft regions changes, instead, for minima between
      which transitions relevant to structural relaxation occur. This may be the reason
      why the soft modes are able to predict spatial heterogeneities in the dynamics.
      Nevertheless, the very softest modes are only weakly correlated with dynamical
      heterogeneities and instead show higher statistical overlap with regions in the
      local minima that would undergo nonaffine rearrangements if subjected to a shear
      deformation. This feature of the supercooled liquid is reminiscent of the
      behavior of nonaffine deformations in amorphous solids, where the very softest
      modes identify the loci of plastic instabilities. 

PMID- 24679307
TI  - Kinetics of nanobubble generation around overheated nanoparticles.
AB  - We report on the formation and growth of nanobubbles around laser-heated gold
      nanoparticles in water. Using a hydrodynamic free-energy model, we show that the
      temporal evolution of the nanobubble radius is asymmetrical: the expansion is
      found to be adiabatic, while the collapse is best described by an isothermal
      evolution. We unveil the critical role of the thermal boundary resistance in the
      kinetics of formation of the nanobubbles: close to the vapor production
      threshold, nanobubble generation is very long, yielding optimal conditions for
      laser-energy conversion. Furthermore, the long appearance times allow
      nanoparticle melting before the onset of vaporization. 

PMID- 24679308
TI  - Physical adsorption: theory of van der Waals interactions between particles and
      clean surfaces.
AB  - van der Waals (vdW) interactions between particles and surfaces are critical for
      the study of physical adsorption. In this work, we develop a method to calculate
      the leading- and higher-order coefficients, describing the dependence of vdW
      interaction on height above the surface. We find that the proposed method can
      produce the vdW coefficients for atoms on surfaces of metals and semiconductors,
      with a mean absolute relative deviation of about 5%. As an important application,
      we study the adsorption energies for rare-gas atoms on noble-metal surfaces by
      combining the present method, which accounts for the long-range part, with
      semilocal density functional theory (DFT), which accounts for the short-range
      part. This combined DFT+vdW approach yields adsorption energies in excellent
      agreement (5%) with experiments. This suggests that the present method may serve
      as a useful dispersion correction to density functional approximations. 

PMID- 24679309
TI  - Stabilization mechanism of ZnO nanoparticles by Fe doping.
AB  - Surprisingly low solubility and toxicity of Fe-doped ZnO nanoparticles is
      elucidated on the basis of first-principles calculations. Various ZnO surfaces
      that could be present in nanoparticles are subject to substitutional Fe doping.
      We show that Fe stabilizes polar instable surfaces, while nonpolar surfaces,
      namely (101_0) and (112_0), remain intact. Polar surfaces can be stabilized
      indirectly through Fe2+-Fe3+ pair-assisted charge transfer, which reduces surface
      polarity and therefore, the solubility in polar solvents. 

PMID- 24679310
TI  - New class of topological superconductors protected by magnetic group symmetries.
AB  - We study a new type of three-dimensional topological superconductor that exhibits
      Majorana zero modes (MZM) protected by a magnetic group symmetry, a combined
      antiunitary symmetry composed of a mirror reflection and time reversal. This new
      symmetry enhances the noninteracting topological classification of a
      superconducting vortex from Z2 to Z, indicating that multiple MZMs can coexist at
      the end of one magnetic vortex of unit flux. Especially, we show that a vortex
      binding two MZMs can be realized on the (001) surface of a topological
      crystalline insulator SnTe with proximity induced BCS Cooper pairing, or in bulk
      superconductor InxSn1-xTe. 

PMID- 24679311
TI  - Spin transfer of quantum information between Majorana modes and a resonator.
AB  - We show that resonant coupling and entanglement between a mechanical resonator
      and Majorana bound states can be achieved via spin currents in a 1D quantum wire
      with strong spin-orbit interactions. The bound states induced by vibrating and
      stationary magnets can hybridize, thus resulting in spin-current induced 4pi
      periodic torques, as a function of the relative field angle, acting on the
      resonator. We study the feasibility of detecting and manipulating Majorana bound
      states with the use of magnetic resonance force microscopy techniques. 

PMID- 24679312
TI  - One-dimensional fermions with neither Luttinger-liquid nor Fermi-liquid behavior.
AB  - It is well known that, generically, one-dimensional interacting fermions cannot
      be described in terms of a Fermi liquid. Instead, they present a different
      phenomenology, that of a Tomonaga-Luttinger liquid: the Landau quasiparticles are
      ill defined, and the fermion occupation number is continuous at the Fermi energy.
      We demonstrate that suitable fine tuning of the interaction between fermions can
      stabilize a peculiar state of one-dimensional matter, which is dissimilar to both
      Tomonaga-Luttinger and Fermi liquids. We propose to call this state a quasi-Fermi
      liquid. Technically speaking, such a liquid exists only when the fermion
      interaction is irrelevant (in the renormalization group sense). The quasi-Fermi
      liquid exhibits the properties of both a Tomonaga-Luttinger liquid and a Fermi
      liquid. Similar to a Tomonaga-Luttinger liquid, no finite-momentum quasiparticles
      are supported by the quasi-Fermi liquid; on the other hand, its fermion
      occupation number demonstrates a finite discontinuity at the Fermi energy, which
      is a hallmark feature of a Fermi liquid. A possible realization of the quasi
      Fermi liquid with the help of cold atoms in an optical trap is discussed. 

PMID- 24679313
TI  - Charge disproportionation without charge transfer in the rare-earth-element
      nickelates as a possible mechanism for the metal-insulator transition.
AB  - We study a model for the metal-insulator (M-I) transition in the rare-earth
      element nickelates RNiO3, based upon a negative charge transfer energy and
      coupling to a rocksaltlike lattice distortion of the NiO6 octahedra. Using exact
      diagonalization and the Hartree-Fock approximation we demonstrate that electrons
      couple strongly to these distortions. For small distortions the system is
      metallic, with a ground state of predominantly d8L character, where L_ denotes a
      ligand hole. For sufficiently large distortions (deltadNi-O~0.05-0.10  A),
      however, a gap opens at the Fermi energy as the system enters a periodically
      distorted state alternating along the three crystallographic axes, with
      (d8L_2)S=0(d8)S=1 character, where S is the total spin. Thus the M-I transition
      may be viewed as being driven by an internal volume "collapse" where the NiO6
      octahedra with two ligand holes shrink around their central Ni, while the
      remaining octahedra expand accordingly, resulting in the (1/2, 1/2, 1/2)
      superstructure observed in x-ray diffraction in the insulating phase. This
      insulating state is an example of charge ordering achieved without any actual
      movement of the charge.

PMID- 24679314
TI  - Exotic magnetic order in the orbital-selective Mott regime of multiorbital
      systems.
AB  - The orbital-selective Mott phase of multiorbital Hubbard models has been
      extensively analyzed before using static and dynamical mean-field approximations.
      In parallel, the properties of block states (antiferromagnetically coupled
      ferromagnetic spin clusters) in Fe-based superconductors have also been much
      discussed. The present effort uses numerically exact techniques in one
      dimensional systems to report the observation of block states within the orbital
      selective Mott phase regime, connecting two seemingly independent areas of
      research, and providing analogies with the physics of double-exchange models. 

PMID- 24679315
TI  - Doping a correlated band insulator: a new route to half-metallic behavior.
AB  - We demonstrate in a simple model the surprising result that turning on an on-site
      Coulomb interaction U in a doped band insulator leads to the formation of a half
      metallic state. In the undoped system, we show that increasing U leads to a first
      order transition at a finite value UAF between a paramagnetic band insulator and
      an antiferomagnetic Mott insulator. Upon doping, the system exhibits half
      metallic ferrimagnetism over a wide range of doping and interaction strengths on
      either side of UAF. Our results, based on dynamical mean field theory, suggest a
      new route to half metallicity, and will hopefully motivate searches for new
      materials for spintronics. 

PMID- 24679316
TI  - Theoretical prediction and spectroscopic fingerprints of an orbital transition in
      CeCu2Si2.
AB  - We show that the heavy-fermion compound CeCu2Si2 undergoes a transition between
      two regimes dominated by different crystal-field states. At low pressure P and
      low temperature T the Ce 4f electron resides in the atomic crystal-field ground
      state, while at high P or T, the electron occupancy and spectral weight is
      transferred to an excited crystal-field level that hybridizes more strongly with
      itinerant states. These findings result from first-principles dynamical-mean
      field-theory calculations. We predict experimental signatures of this orbital
      transition in x-ray spectroscopy. The corresponding fluctuations may be
      responsible for the second high-pressure superconducting dome observed in this
      and similar materials. 

PMID- 24679317
TI  - Universal entanglement crossover of coupled quantum wires.
AB  - We consider the entanglement between two one-dimensional quantum wires (Luttinger
      liquids) coupled by tunneling through a quantum impurity. The physics of the
      system involves a crossover between weak and strong coupling regimes
      characterized by an energy scale TB, and methods of conformal field theory
      therefore cannot be applied. The evolution of the entanglement in this crossover
      has led to many numerical studies, but has remained little understood,
      analytically or even qualitatively. We argue in this Letter that the correct
      universal scaling form of the entanglement entropy S (for an arbitrary interval
      of length L containing the impurity) is ?S/? ln L=f(LTB). In the special case
      where the coupling to the impurity can be refermionized, we show how the
      universal function f(LTB) can be obtained analytically using recent results on
      form factors of twist fields and a defect massless-scattering formalism. Our
      results are carefully checked against numerical simulations. 

PMID- 24679318
TI  - Spin pumping and inverse spin Hall effect in platinum: the essential role of spin
      memory loss at metallic interfaces.
AB  - Through combined ferromagnetic resonance, spin pumping, and inverse spin Hall
      effect experiments in Co|Pt bilayers and Co|Cu|Pt trilayers, we demonstrate
      consistent values of lsfPt=3.4+/-0.4  nm and thetaSHEPt=0.056+/-0.010 for the
      respective spin diffusion length and spin Hall angle for Pt. Our data and model
      emphasize the partial depolarization of the spin current at each interface due to
      spin-memory loss. Our model reconciles the previously published spin Hall angle
      values and explains the different scaling lengths for the ferromagnetic damping
      and the spin Hall effect induced voltage. 

PMID- 24679319
TI  - Solar nanocomposites with complementary charge extraction pathways for electrons
      and holes: Si embedded in ZnS.
AB  - We propose that embedding silicon nanoparticles (NP) into amorphous,
      nonstoichiometric ZnS leads to promising nanocomposites for solar energy
      conversion. Using ab initio molecular dynamics simulations we show that, upon
      high temperature amorphization of the host chalcogenide, sulfur atoms are drawn
      to the NP surface. We find that the sulfur content may be engineered to form a
      type II heterojunction, with complementary charge transport channels for
      electrons and holes, and that sulfur capping is beneficial to lower the
      nanoparticle gap, with respect to that of NPs embedded in oxide matrices. Our
      analysis is conducted using density functional theory with local and hybrid
      functionals and many body perturbation theory at the GW level. 

PMID- 24679320
TI  - Valley-polarized quantum anomalous Hall effect in silicene.
AB  - We find theoretically a new quantum state of matter-the valley-polarized quantum
      anomalous Hall state in silicene. In the presence of Rashba spin-orbit coupling
      and an exchange field, silicene hosts a quantum anomalous Hall state with Chern
      number C=2. We show that through tuning the Rashba spin-orbit coupling, a
      topological phase transition results in a valley-polarized quantum anomalous Hall
      state, i.e., a quantum state that exhibits the electronic properties of both the
      quantum valley Hall state (valley Chern number Cv=3) and quantum anomalous Hall
      state with C=-1. This finding provides a platform for designing dissipationless
      valleytronics in a more robust manner. 

PMID- 24679321
TI  - Measurement of an enhanced superconducting phase and a pronounced anisotropy of
      the energy gap of a strained FeSe single layer in FeSe/Nb:SrTiO3/KTaO3
      heterostructures using photoemission spectroscopy.
AB  - Single-layer FeSe films with an extremely expanded in-plane lattice constant of
      3.99+/-0.02  A are fabricated by epitaxially growing FeSe/Nb:SrTiO3/KTaO3
      heterostructures and studied by in situ angle-resolved photoemission
      spectroscopy. Two elliptical electron pockets at the Brillouin zone corner are
      resolved with negligible hybridization between them, indicating that the symmetry
      of the low-energy electronic structure remains intact as a freestanding single
      layer FeSe, although it is on a substrate. The superconducting gap closes at a
      record high temperature of 70 K for the iron-based superconductors. Intriguingly,
      the superconducting gap distribution is anisotropic but nodeless around the
      electron pockets, with minima at the crossings of the two pockets. Our results
      place strong constraints on current theories. 

PMID- 24679322
TI  - Detection of time-reversal symmetry breaking in the noncentrosymmetric
      superconductor Re6Zr using muon-spin spectroscopy.
AB  - We have investigated the superconducting state of the noncentrosymmetric compound
      Re6Zr using magnetization, heat capacity, and muon-spin relaxation or rotation
      (MUSR) measurements. Re6Zr has a superconducting transition temperature,
      Tc=6.75+/-0.05  K. Transverse-field MUSR experiments, used to probe the
      superfluid density, suggest an s-wave character for the superconducting gap.
      However, zero and longitudinal-field MUSR data reveal the presence of spontaneous
      static magnetic fields below Tc indicating that time-reversal symmetry is broken
      in the superconducting state and an unconventional pairing mechanism. An analysis
      of the pairing symmetries identifies the ground states compatible with time
      reversal symmetry breaking. 

PMID- 24679323
TI  - Direct observation of magnetic metastability in individual iron nanoparticles.
AB  - X-ray photoemission electron microscopy combined with x-ray magnetic circular
      dichroism is used to study the magnetic properties of individual iron
      nanoparticles with sizes ranging from 20 down to 8 nm. While the
      magnetocrystalline anisotropy of bulk iron suggests superparamagnetic behavior in
      this size range, ferromagnetically blocked particles are also found at all sizes.
      Spontaneous transitions from the blocked state to the superparamagnetic state are
      observed in single particles and suggest that the enhanced magnetic energy
      barriers in the ferromagnetic particles are due to metastable, structurally
      excited states with unexpected life times. 

PMID- 24679324
TI  - Nonfrustrated interlayer order and its relevance to the Bose-Einstein
      condensation of magnons in BaCuSi2O6.
AB  - Han purple (BaCuSi2O6) is not only an ancient pigment, but also a valuable model
      material for studying Bose-Einstein condensation of magnons in high magnetic
      fields. Using precise low-temperature structural data and extensive density
      functional calculations, we elucidate magnetic couplings in this compound. The
      resulting magnetic model comprises two types of nonequivalent spin dimers, in
      excellent agreement with the Cu63,65 nuclear magnetic resonance data. We further
      argue that leading interdimer couplings connect the upper site of one dimer to
      the bottom site of the contiguous dimer, and not the upper-to-upper and bottom-to
      bottom sites, as assumed previously. This finding is verified by inelastic
      neutron scattering data and implies the lack of frustration between the layers of
      spin dimers in BaCuSi2O6, thus challenging existing theories of the two
      dimensional-like Bose-Einstein condensation of magnons in this compound. 

PMID- 24679325
TI  - Electronic excitations of a magnetic impurity state in the diluted magnetic
      semiconductor (Ga,Mn)As.
AB  - The electronic structure of doped Mn in (Ga,Mn)As is studied by resonant
      inelastic x-ray scattering. From configuration-interaction cluster-model
      calculations, the line shapes of the Mn L3 resonant inelastic x-ray scattering
      spectra can be explained by d-d excitations from the Mn ground state dominated by
      charge-transferred states, in which hole carriers are bound to the Mn impurities,
      rather than a pure acceptor Mn2+ ground state. Unlike archetypical d-d
      excitation, the peak widths are broader than the experimental energy resolution.
      We attribute the broadening to a finite lifetime of the d-d excitations, which
      decay rapidly to electron-hole pairs in the host valence and conduction bands
      through the hybridization of the Mn 3d orbital with the ligand band. 

PMID- 24679326
TI  - High resolution coherent population trapping on a single hole spin in a
      semiconductor quantum dot.
AB  - We report high resolution coherent population trapping on a single hole spin in a
      semiconductor quantum dot. The absorption dip signifying the formation of a dark
      state exhibits an atomic physicslike dip width of just 10 MHz. We observe
      fluctuations in the absolute frequency of the absorption dip, evidence of very
      slow spin dephasing. We identify the cause of this process as charge noise by,
      first, demonstrating that the hole spin g factor in this configuration (in-plane
      magnetic field) is strongly dependent on the vertical electric field, and second,
      by characterizing the charge noise through its effects on the optical transition
      frequency. An important conclusion is that charge noise is an important hole spin
      dephasing process. 

PMID- 24679327
TI  - Exciton dynamics in carbon nanotubes: from the Luttinger liquid to harmonic
      oscillators.
AB  - We show that the absorption spectrum in semiconducting nanotubes can be
      determined using the bosonization technique combined with mean-field theory and a
      harmonic approximation. In this framework, a multiple band semiconducting
      nanotube reduces to a system of weakly coupled harmonic oscillators. We also find
      that gaps of any size destroy the Luttinger liquid phase in single-walled carbon
      nanotubes and give rise to electron density fluctuations that resemble excitons
      built from quasiparticles. Interband processes, such as multiple exciton
      generation, become progressively weaker as the length to diameter ratio grows
      larger. 

PMID- 24679328
TI  - Radiative topological states in resonant photonic crystals.
AB  - We present a theory of topological edge states in one-dimensional resonant
      photonic crystals with a compound unit cell. Contrary to the conventional
      electronic topological states, the modes under consideration are radiative; i.e.,
      they decay in time due to the light escape through the structure boundaries. We
      demonstrate that the edge states survive despite their radiative decay and can be
      detected both in time- and frequency-dependent light reflection. 

PMID- 24679329
TI  - Nanoparticle diffusion in polymer nanocomposites.
AB  - Large-scale molecular dynamics simulations show that nanoparticle (NP)
      diffusivity in weakly interacting mixtures of NPs and polymer melts has two very
      different classes of behavior depending on their size. NP relaxation times and
      their diffusivities are completely described by the local, Rouse dynamics of the
      polymer chains for NPs smaller than the polymer entanglement mesh size. The
      motion of larger NPs, which are comparable to the entanglement mesh size, is
      significantly slowed by chain entanglements, and is not describable by the Stokes
      Einstein relationship. Our results are in essentially quantitative agreement with
      a force-level generalized Langevin equation theory for all the NP sizes and chain
      lengths explored, and imply that for these lightly entangled systems, activated
      NP hopping is not important. 

PMID- 24679330
TI  - Slow relaxation and aging phenomena at the nanoscale in granular materials.
AB  - Granular matter exhibits a rich variety of dynamic behaviors, for which the role
      of thermal fluctuations is usually ignored. Here we show that thermal
      fluctuations can pronouncedly affect contacting nanoscale asperities at grain
      interfaces and brightly manifest themselves through the influence on nonlinear
      acoustic effects. The proposed mechanism based on intrinsic bistability of
      nanoscale contacts comprises a wealth of slow-dynamics regimes including slow
      relaxations and aging as universal properties of a wide class of systems with
      metastable states. 

PMID- 24679331
TI  - Comment on "Uniqueness of the equation for quantum state vector collapse".

PMID- 24679332
TI  - Gao and Muller reply.

PMID- 24679333
TI  - Endocrine and metabolic mechanisms linking postpartum glucose with early
      embryonic and foetal development in dairy cows.
AB  - Milk and milk solids production per cow is increasing annually in dairy systems.
      Peak milk production is in early lactation when the uterus and ovary are
      recovering from the previous pregnancy. The competing processes of milk
      production and restoration of reproductive function can be at odds, particularly
      if unique homeorhetic mechanisms that typify early lactation become imbalanced
      and cows experience metabolic disease. Homeorhesis leads to an increase in the
      synthesis of glucose that is irreversibly lost to milk lactose. Irreversible loss
      of glucose during lactation can invoke an endocrine and metabolic state that
      impinges upon postpartum uterine health, oestrous cyclicity and subsequent
      establishment of pregnancy. The first 30 days postpartum may be most critical in
      terms of the impact that metabolites and metabolic hormones have on reproduction.
      Depressed immune function caused in part by the postpartum metabolic profile
      leads to a failure in uterine involution and uterine disease. Oestrous cyclicity
      (interval to first ovulation and subsequent periodicity) is affected by the same
      hormones and metabolites that control postpartum immune function. Slower growth
      of the embryo or foetus perhaps explained by the unique metabolic profile during
      lactation may predispose cows to pregnancy loss. Understanding homeorhetic
      mechanisms that involve glucose and collectively affect postpartum uterine
      health, oestrous cyclicity and the establishment of pregnancy should lead to
      methods to improve postpartum fertility in dairy cows. 

PMID- 24679334
TI  - Spectral detection of thalassemia: a preliminary study.
AB  - BACKGROUND: Thalassemias (Thal) are forms of inherited autosomal recessive blood
      disorders arising out of mutations in the chromosomes 11 or 16. These disorders
      lead to poor oxygen delivery to blood vessels and consequent splenomegaly, bone
      deformities, and shorter life spans. The most common detection methods for Thal
      are complete blood count (CBC) followed by electrophoresis and molecular
      diagnosis methods, such as high-performance liquid chromatography (HPLC) and
      polymerase chain reaction (PCR) genotyping. These methods involve sophisticated
      instrumentations and are cumbersome and expensive. RESULTS: In this study an
      innovative spectral detection method, based on the fluorescence spectra of a set
      of biomolecules (tyrosine, tryptophan, nicotinamide adenine dinucleotide, and
      flavin adenine dinucleotide and porphyrins) found in blood components is
      presented. An algorithm based on the spectral features of such biomolecules of
      blood components of 20 Thal patients (10 female and 10 male) and 18 age adjusted
      normal controls (4 female and 14 male) demonstrate reasonable level of
      classification with sensitivity and specificity values exceeding 90%. CONCLUSION:
      This new technique could be of significant value for Thal detection, diagnosis,
      and subsequent genetic counselling and could be adapted for use in small primary
      health centres.

PMID- 24679335
TI  - PEGylated, NH2-terminated PAMAM dendrimers: a microscopic view from atomistic
      computer simulations.
AB  - Poly(amido amine) (PAMAM) dendrimers are promising nanocarriers in a wide range
      of biomedical applications including gene and drug delivery and as imaging
      agents. They have unique structural properties and are characterized by high size
      uniformity, low polydispersity, and a large number of modifiable surface groups.
      Drug-dendrimer systems are usually further modified through the conjugation of
      ligands in order to confer the carriers' specific characteristics designed to
      enhance their efficacy. The chemistry and structure of the solvated ligand
      conjugated dendrimer nanocarriers (DNCs) will dictate how they interact with the
      physiological environment and, therefore, their fate and function. Understanding
      the microstructures of ligand-conjugated DNCs is, therefore, of great relevance
      within the context of drug delivery applications. In this work, we investigate
      the effect of poly(ethylene glycol) (PEG) on the microstructure of solvated, NH2
      terminated PAMAM DNCs using fully atomistic molecular dynamics simulations.
      Several variables including dendrimer generation (2-5), PEGylation density (0
      50%), and PEG Mw (500 and 1000) were investigated. The results obtained showed a
      good match with available experimental results, including size as a function of
      dendrimer degeneration (G2NH2-G5NH2). No back-folding is observed for PAMAM
      dendrimers with generation lower than G5NH2. G2NH2 and G3NH2 showed a dense
      packed, nonglobular structure, and G4NH2 and G5NH2 have a segmented, "open"
      structure. Our results help settle a long-standing debate with respect to "back
      folding" as the microstructural information obtained here is reconciled with
      experimental results. PEGylation was found to influence the microstructure in a
      different way, including an expected increase in the overall size of the DNCs,
      while not affecting much the solvation of unmodified terminal (primary) amines.
      It also serves to expand the core of dendrimers, reduce the surface charge, and
      change solvation behavior of different generation branching amines. We show that
      the microstructure of a PEG layer with the same number of repeat units can be
      significantly altered by changing the grafting density and size of PEG. Potential
      consequences in the design of PEGylated dendrimers for drug delivery and
      targeting are discussed based on the obtained microstructural information. 

PMID- 24679337
TI  - The role of BRAF V600E mutation as a potential marker for prognostic
      stratification of papillary thyroid carcinoma: a long-term follow-up study.
AB  - Abstract Papillary carcinoma is the most prevalent malignancy of thyroid gland,
      and its incidence has been recently increased. The BRAF(V600E) mutation is the
      most frequent genetic alteration in papillary thyroid carcinoma (PTC). The role
      of BRAF(V600E) mutation as a potential prognostic factor has been controversially
      reported in different studies, with short-term follow-up. In this study, we
      evaluated the role of BRAF(V600E) mutation as a potential marker for prognostic
      stratification of patients with PTC in long-term follow-up. We studied 69 PTC
      patients with a mean follow-up period of 63.9 months (median: 60 m). The
      BRAF(V600E) mutation was analyzed by PCR-single-strand conformational
      polymorphism and sequencing. The correlation between the presence or absence of
      the BRAF(V600E) mutation, clinicopathological features and prognosis of PTC
      patients were studied. The BRAF(V600E) mutation was found in 28 of 69 (40.6%) PTC
      patients, and it was significantly more frequent in older patients (p < 0.001),
      in advanced tumor stages (p = 0.006) and in patients with history of radiation
      exposure (p = 0.037). Incomplete response to treatment in PTC patients was
      significantly correlated with certain clinicopathological characteristics (follow
      up time, distant metastases, advanced stage, first thyroglobulin (fTg) level,
      history of reoperation and external radiotherapy and delay in iodine therapy) but
      it was not related to the presence of BRAF(V600E) mutation. Prevalence of
      BRAF(V600E) mutation was 40.6% in patients with papillary thyroid cancer in
      northeast of Iran. The BRAF(V600E) mutation was associated with older age and
      advanced tumor stage but was not correlated with incomplete response during
      follow-up. 

PMID- 24679338
TI  - The physical health status, service utilisation and barriers to accessing care
      for asylum seekers residing in the community: a systematic review of the
      literature.
AB  - OBJECTIVE: To document physical health problems that asylum seekers experience on
      settlement in the community and to assess their utilisation of healthcare
      services and barriers to care, in an international context. METHODS: A systematic
      review of quantitative and qualitative studies was undertaken according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MEDLINE,
      PsycINFO, Embase and CINAHL databases were searched from 2002 to October 2012,
      focusing on adult asylum seekers residing in the community in high-income
      countries. RESULTS: The search yielded 1499 articles, of which 32 studies met the
      inclusion criteria - 23 quantitative and nine qualitative. Asylum seekers had
      complex health profiles spanning a range of infectious diseases, chronic non
      communicable conditions, and reproductive-health issues. They appeared to utilise
      health services at a higher rate than the host population, yet faced significant
      barriers to care. CONCLUSION: The findings of this study highlight the health
      inequities faced by asylum seekers residing in the communities of host countries,
      internationally. National data on asylum seekers' health profiles, service
      utilisation and barriers to care, as well as cross-country policy comparisons,
      are urgently required for the development of effective Australian health programs
      and evidence-based policy. What is known about the topic? The clinical and
      political focus of asylum seekers' health has largely been on the higher
      incidence of mental disorders and the impact of immigration detention. Since
      policy changes made in late 2011, an increasing number of asylum seekers have
      been permitted to live in the community while their claims are processed. There
      is a paucity of research exploring the physical health needs of asylum seekers
      residing in the community. What does this paper add? The international literature
      highlights the complexity of asylum seekers' health profiles. Although they
      appear to utilise health services at a higher rate than the host population, they
      continue to face many barriers to care. What are the implications for
      practitioners? Studies that explore policy options, including cross-country
      comparisons of health policy and guidelines that improve health outcomes, to
      foster equity of access and reduce health inequalities between asylum seekers and
      the host population are urgently required.

PMID- 24679339
TI  - Reactive molecular dynamics simulation on the disintegration of Kapton, POSS
      polyimide, amorphous silica, and teflon during atomic oxygen impact using the
      ReaxFF reactive force-field method.
AB  - Atomic oxygen (AO) is the most abundant element in the low Earth orbit (LEO). It
      is the result of the dissociation of molecular oxygen by ultraviolet radiation
      from the sun. In the LEO, it collides with the materials used on spacecraft
      surfaces and causes degradation of these materials. The degradation of the
      materials on the surface of spacecrafts at LEO has been a significant problem for
      a long time. Kapton polyimide, polyhedral oligomeric silsesquioxane (POSS),
      silica, and Teflon are the materials extensively used in spacecraft industry, and
      like many other materials used in spacecraft industry, AO collision degradation
      is an important issue in their applications on spacecrafts. To investigate the
      surface chemistry of these materials in exposure to space AO, a computational
      chemical evaluation of the Kapton polyimide, POSS, amorphous silica, and Teflon
      was performed in separate simulations under similar conditions. For performing
      these simulations, the ReaxFF reactive force-field program was used, which
      provides the computational speed required to perform molecular dynamics (MD)
      simulations on system sizes sufficiently large to describe the full chemistry of
      the reactions. Using these simulations, the effects of AO impact on different
      materials and the role of impact energies, the content of material, and
      temperature of material on the behavior of the materials are studied. The ReaxFF
      results indicate that Kapton is less resistant than Teflon toward AO damage.
      These results are in good agreement with experiment. These simulations indicate
      that the amorphous silica shows the highest stability among these materials
      before the start of the highly exothermic silicon oxidation. We have verified
      that adding silicon to the bulk of the Kapton structure enhances the stability of
      the Kapton against AO impact. Our canonical MD simulations demonstrate that an
      increase in the heat transfer in materials during AO impact can provide a
      considerable decrease in the disintegration of the material. This effect is
      especially relevant in silica AO collision. Considerable experimental efforts
      have been undertaken to minimize such AO-based degradations. As our simulations
      demonstrate, ReaxFF can provide a cost-effective screening tool for future
      material optimization. 

PMID- 24679336
TI  - Clinical effectiveness of manual therapy for the management of musculoskeletal
      and non-musculoskeletal conditions: systematic review and update of UK evidence
      report.
AB  - BACKGROUND: This systematic review updated and extended the "UK evidence report"
      by Bronfort et al. (Chiropr Osteopath 18:3, 2010) with respect to
      conditions/interventions that received an 'inconclusive' or 'negative' evidence
      rating or were not covered in the report. METHODS: A literature search of more
      than 10 general medical and specialised databases was conducted in August 2011
      and updated in March 2013. Systematic reviews, primary comparative studies and
      qualitative studies of patients with musculoskeletal or non-musculoskeletal
      conditions treated with manual therapy and reporting clinical outcomes were
      included. Study quality was assessed using standardised instruments, studies were
      summarised, and the results were compared against the evidence ratings of
      Bronfort. These were either confirmed, updated, or new categories not assessed by
      Bronfort were added. RESULTS: 25,539 records were found; 178 new and additional
      studies were identified, of which 72 were systematic reviews, 96 were randomised
      controlled trials, and 10 were non-randomised primary studies. Most
      'inconclusive' or 'moderate' evidence ratings of the UK evidence report were
      confirmed. Evidence ratings changed in a positive direction from inconclusive to
      moderate evidence ratings in only three cases (manipulation/mobilisation [with
      exercise] for rotator cuff disorder; spinal mobilisation for cervicogenic
      headache; and mobilisation for miscellaneous headache). In addition, evidence was
      identified on a large number of non-musculoskeletal conditions not previously
      considered; most of this evidence was rated as inconclusive. CONCLUSIONS:
      Overall, there was limited high quality evidence for the effectiveness of manual
      therapy. Most reviewed evidence was of low to moderate quality and inconsistent
      due to substantial methodological and clinical diversity. Areas requiring further
      research are highlighted.

PMID- 24679340
TI  - Platelet adhesion changes during storage studied with a novel method using flow
      cytometry and protein-coated beads.
AB  - The aim of the present study was to set up and evaluate a novel method for
      studies of platelet adhesion and activation in blood and platelet suspensions
      such as platelet concentrate (PC) samples using protein-coated polystyrene beads
      and flow cytometry. To demonstrate its usefulness, we studied PCs during storage.
      PCs were prepared by aphaeresis technique (n = 7). Metabolic variables and
      platelet function was measured on day 1, 5, 7 and 12 of storage. Spontaneous and
      TRAP-6-induced adhesion to fibrinogen- and collagen-coated beads was analyzed by
      flow cytometry. P-selectin and phosphatidyl serine (PS) expression was assessed
      on platelets bound to beads as well as on non-adherent platelets. Platelet
      adhesion to fibrinogen beads had increased by day 12 and adhesion to collagen
      beads at day 7 of storage (p < 0.05). TRAP-6 stimulation significantly increased
      the platelet adhesion to fibrinogen beads (p < 0.05) as well as the P-selectin
      and PS exposure on platelets bound to beads (p < 0.01) during the first 7 days of
      storage, but by day 12, significant changes were no longer induced by TRAP-6
      stimulation. We demonstrate that our adhesion assay using protein-coated
      polystyrene beads can be used to assess the adhesion properties of platelets
      during storage without the addition of red blood cells. Therefore it may offer a
      useful tool for future studies of platelet adhesive capacity in transfusion
      medicine and other settings.

PMID- 24679341
TI  - Effect of exercise on dual-task and balance on elderly in multiple disease
      conditions.
AB  - Investigations on how exercise and physical activity affect dual-task (DT)
      performance in the elderly are growing rapidly due to the fact that DT activities
      are commonplace with activities of daily living. Preliminary evidence has shown
      the benefit in exercise on DT balance, though it is unclear to what extent the
      effect exercise has on DT performance in elderly subjects with disease
      conditions, including subjects with a high risk of falls. Hence, the objective of
      this study was to critically review the existing evidence of a potential
      relationship between exercise and improvement of static and dynamic balance
      during DT conditions as well as secondary outcomes in elderly subjects with
      different disease conditions. A systematic search using online databases was
      performed to source documents. Inclusion criteria sourced articles classified as
      randomized controlled trials (RCT), controlled trials (CT) and uncontrolled
      trials (UT). Moreover, the studies had to administrate an exercise or physical
      activity protocol in the intervention. Seventeen studies met the eligibility
      criteria and were comprised of 12 RCTs, 3 CTs, and 2 UTs. Overall, 13 studies
      supported exercise being effective to improve parameters of static and dynamic
      balance during single or DT conditions. Despite the heterogeneity of pathologic
      conditions, exercise showed similar benefits to improve function in two main
      areas: neurological conditions and frailty conditions. The lack of a common
      method to assess DT performance limited the ability to compare different
      interventions directly. Future research is warranted to study the optimal dose
      and exercise modalities to best reduce the risk of falls in the elderly with
      multiple disease conditions. 

PMID- 24679342
TI  - Partitioning of polybrominated diphenyl ethers to dissolved organic matter
      isolated from Arctic surface waters.
AB  - Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardant
      that is distally transported to the Arctic. Little is known about the fate of
      PBDEs in Arctic surface waters, especially in the presence of dissolved organic
      matter (DOM). DOM has been shown to interact with hydrophobic organic
      contaminants and can alter their mobility, bioavailability, and degradation in
      the environment. In this study, the partitioning of six PBDE congeners between
      Arctic DOM (isolated via solid phase extraction) and water was measured using the
      aqueous solubility enhancement method. Measured dissolved organic carbon (DOC)
      water partition coefficient (KDOC) values were nearly an order of magnitude lower
      than previously reported values for the same PBDE congeners in soil or commercial
      organic matter, ranging from 10(3.97) to 10(5.16) L kg(-1) of organic carbon.
      Measured results compared favorably with values calculated using polyparameter
      linear free energy models for Suwannee River fulvic acid. Log KDOC values
      increased with increasing PBDE hydrophobicity. Slightly lower than expected
      values were observed for the highest brominated congeners, which we attribute to
      steric hindrance. This study is the first to comprehensively measure KDOC values
      for a range of PBDE congeners with DOM isolated from Arctic surface waters. 

PMID- 24679344
TI  - Thromboembolism in lung cancer - an area of urgent unmet need.
AB  - INTRODUCTION: Thromboembolism is common in lung cancer. Current
      thromboprophylaxis guidelines lack specific recommendations for appropriate
      strategies in this high thrombotic risk patient cohort. We profiled lung cancer
      patients receiving anti-cancer therapy. Thromboembolism incidence and
      thromboembolism-related mortality rates are reported and we explored patient,
      disease, and treatment-related risk factors associated with higher thrombotic
      rates. METHODS: Retrospective review of lung cancer patients referred to a
      Comprehensive Cancer Centre between 01/07/2011 and 30/06/2012 for anti-cancer
      therapy. Data were collected from medical, pharmacy, pathology and diagnostic
      imaging electronic records. RESULTS: After a median follow up of 10 months
      (range: 0.03-32 months), 24/222 patients (10.8%) had developed radiologically
      confirmed thromboembolism; 131 events per 1000 person-years (95%CI 87-195).
      Thromboembolism occurred equally in patients with non-small cell and small cell
      lung cancer (10.8% and 10.5% respectively), and more frequently among patients
      with adenocarcinoma compared to squamous cell carcinoma (14.7% and 5.3%
      respectively). Chemotherapy-treated patients experienced thromboembolism more
      often than patients who did not receive chemotherapy (HR 5.7 95%CI 2.2-14.8).
      Radiotherapy was also associated with more frequent thromboembolism (HR 5.2 95%CI
      2.0-13.2). New lung cancer diagnosis, presence of metastatic disease, second
      primary malignancy and Charlson Index >= 5 were also associated with higher rates
      of thromboembolism. Importantly, pharmacological thromboprophylaxis (P-TP) was
      not routinely or systematically prescribed for ambulant lung cancer patients
      during any treatment phase, at this institution. The majority (83%) of
      thromboembolic events occurred in the ambulatory care setting. CONCLUSION:
      Morbidity and mortality from thromboembolism occurs frequently in lung cancer.
      Thromboprophylaxis guidelines should be developed for the ambulatory care
      setting.

PMID- 24679343
TI  - Sphingosine-1-phosphate receptors control B-cell migration through signaling
      components associated with primary immunodeficiencies, chronic lymphocytic
      leukemia, and multiple sclerosis.
AB  - BACKGROUND: Five different G protein-coupled sphingosine-1-phosphate (S1P)
      receptors (S1P1-S1P5) regulate a variety of physiologic and pathophysiologic
      processes, including lymphocyte circulation, multiple sclerosis (MS), and cancer.
      Although B-lymphocyte circulation plays an important role in these processes and
      is essential for normal immune responses, little is known about S1P receptors in
      human B cells. OBJECTIVE: To explore their function and signaling, we studied B
      cell lines and primary B cells from control subjects, patients with leukemia,
      patients with S1P receptor inhibitor-treated MS, and patients with primary
      immunodeficiencies. METHODS: S1P receptor expression was analyzed by using
      multicolor immunofluorescence microscopy and quantitative PCR. Transwell assays
      were used to study cell migration. S1P receptor internalization was visualized by
      means of time-lapse imaging with fluorescent S1P receptor fusion proteins
      expressed by using lentiviral gene transfer. B-lymphocyte subsets were
      characterized by means of flow cytometry and immunofluorescence microscopy.
      RESULTS: Showing that different B-cell populations express different combinations
      of S1P receptors, we found that S1P1 promotes migration, whereas S1P4 modulates
      and S1P2 inhibits S1P1 signals. Expression of CD69 in activated B lymphocytes and
      B cells from patients with chronic lymphocytic leukemia inhibited S1P-induced
      migration. Studying B-cell lines, normal B lymphocytes, and B cells from patients
      with primary immunodeficiencies, we identified Bruton tyrosine kinase, beta
      arrestin 2, LPS-responsive beige-like anchor protein, dedicator of cytokinesis 8,
      and Wiskott-Aldrich syndrome protein as critical signaling components downstream
      of S1P1. CONCLUSION: Thus S1P receptor signaling regulates human B-cell
      circulation and might be a factor contributing to the pathology of MS, chronic
      lymphocytic leukemia, and primary immunodeficiencies.

PMID- 24679345
TI  - Laboratory and experimental hut evaluation of a long-lasting insecticide treated
      blanket for protection against mosquitoes.
AB  - BACKGROUND: Long-lasting insecticide treated blankets (LLIBs) may provide
      additional protection against malaria where use of long lasting insecticidal nets
      (LLIN) is low or impractical such as in disaster or emergency situations.
      METHODS: Initial efficacy testing of a new candidate LLIB was carried out at
      LSHTM and KCMUCo, before and after washing, in cone and ball bioassays and arm-in
      cage tests against pyrethroid susceptible Anopheles gambiae. A small scale field
      trial was conducted using veranda-trap experimental huts in northern Tanzania
      against wild An. arabiensis and Culex quinquefasciatus mosquitoes. Treatments
      included unwashed and 5 times washed permethrin treated LLIB and blankets hand
      treated with permethrin (ITB), untreated blankets, and a holed unwashed Olyset
      net. RESULTS: Cone test mortality was 75% for LLIB when unwashed, but decreased
      to 32% after 5 washes and <10% after 10 washes. In arm-in-cage tests protection
      against biting was 100% for LLIBs regardless of the number of washes while
      reduction in landings was 79% when unwashed, 75% after 5 washes, but declined to
      41% after 10 and 33% after 20 washes. In ball bioassays using pyrethroid
      resistant An. arabiensis, mortality was low in all treatments (<35%) and there
      was no significant difference in mortality between Olyset net, LLIB or ITB (p >
      0.05). Percentage mortality of An. arabiensis in huts with LLIB unwashed (26%)
      was not statistically different to Olyset net (31%, p = 0.5). The 5 times washed
      LLIB reduced blood-feeding by 49% which was equivalent to Olyset net (p > 0.086).
      There was no significant difference in percentage blood-feeding between LLIB and
      ITB unwashed or 5 times washed (p = 0.147 and p = 0.346 respectively). The 5
      times washed LLIB reduced blood-feeding of Culex quinquefasciatus by 40%,
      although the Olyset provided the greatest protection with 85% inhibition. ELISA
      analysis of a sub-sample of blood fed mosquitoes showed that not all had fed on
      humans in the huts, therefore blood-feeding inhibition may have been
      underestimated. CONCLUSIONS: This trial demonstrated the potential of LLIBs to
      provide substantial personal protection even against pyrethroid resistant
      mosquitoes. LLIBs may prove particularly useful where LLINs are unsuitable or net
      usage is low.

PMID- 24679346
TI  - Sinking-magnetic microparticles prepared by the electrospray method for enhanced
      gastric antimicrobial delivery.
AB  - A targeted oral drug delivery system is useful to improve the treatment of
      gastrointestinal diseases. A high density sinking dosage form can sink to the
      bottom of the stomach near the pylori sections to enhance gastric retention.
      However, it is difficult to achieve a high density sinking system using the
      traditional technology. In the current study, novel stomach-specific sinking
      magnetic microparticles (SMMPs) were prepared via the monoaxial electrospray
      method for enhanced gastric antimicrobial delivery. The size of SMMPs was
      approximately 5 MUm, and the Fe3O4 nanoparticles were observed in the SMMPs by
      transmission electron microscopy (TEM). The density of SMMPs increased as the
      concentration of Fe3O4 nanoparticles in the electrospray inlet flow increased,
      with the maximum true density of approximately 3.52 g/cm(3). The SMMPs displayed
      strong magnetism in vitro and in vivo. They can settle down in water within 120 s
      in vitro, and the settling time decreased to 20 s under a magnetic field.
      Furthermore, an in vivo gamma scintigraphy study demonstrated that (131)I labeled
      SMMPs were retained in the stomach for over 8 h, and an external permanent magnet
      can increase their gastric retention time even further. Using Helicobacter pylori
      as a model bacterium, amoxicillin-loaded SMMPs exhibited a significantly greater
      eradication of H. pylori compared to the free drug, in vivo. Our results
      suggested that electrospray is an effective technique to prepare the high density
      gastroretentive dosage forms. We have shown that stomach-specific SMMPs can
      supply better treatment for H. pylori infections and have the potential to be
      used in clinical practice. 

PMID- 24679347
TI  - Commentary: research in neurodevelopmental disorders that takes biology and
      behavior to heart.

PMID- 24679348
TI  - Bone mineral density in adults with Down syndrome, intellectual disability, and
      nondisabled adults.
AB  - Individuals with intellectual disability (ID) or Down syndrome (DS) may be at
      greater risk of osteoporosis. The purpose of this study was to compare bone
      mineral density (BMD) of DS, ID, and non-intellectually disabled (NID)
      populations. In each group, 33 participants between the ages of 28 and 60 years
      were compared. BMD was measured with dual-energy x-ray absorptiometry (DXA)
      scans. BMD (p < .0001) between all groups was significantly different.
      Participants with DS had significantly lower BMD compared to NID participants.
      Individuals with ID had significantly lower BMD compared to NID subjects.
      Participants with DS had the lowest BMD of all groups. DS subjects display a
      greater risk for osteoporosis than ID subjects or control populations.

PMID- 24679350
TI  - Social approach and emotion recognition in fragile X syndrome.
AB  - Evidence is emerging that individuals with Fragile X syndrome (FXS) display
      emotion recognition deficits, which may contribute to their significant social
      difficulties. The current study investigated the emotion recognition abilities,
      and social approachability judgments, of FXS individuals when processing
      emotional stimuli. Relative to chronological age- (CA-) and mental age- (MA-)
      matched controls, the FXS group performed significantly more poorly on the
      emotion recognition tasks, and displayed a bias towards detecting negative
      emotions. Moreover, after controlling for emotion recognition deficits, the FXS
      group displayed significantly reduced ratings of social approachability. These
      findings suggest that a social anxiety pattern, rather than poor socioemotional
      processing, may best explain the social avoidance observed in FXS.

PMID- 24679349
TI  - Children with chromosome 22q11.2 deletion syndrome exhibit impaired spatial
      working memory.
AB  - Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown
      to have impairments in processing spatiotemporal information. The authors
      examined whether children with 22q11.2DS exhibit impairments in spatial working
      memory performance due to these weaknesses, even when controlling for maintenance
      of attention. Children with 22q11.2DS (n  =  47) and typically developing
      controls (n  =  49) ages 6-15 years saw images within a grid and after a delay,
      then indicated the positions of the images in the correct temporal order.
      Children with 22q11.2DS made more spatial and temporal errors than controls.
      Females with 22q11.2DS made more spatial and temporal errors than males. These
      results extend findings of impaired spatiotemporal processing into the memory
      domain in 22q11.2DS by documenting their influence on working memory performance.

PMID- 24679351
TI  - Clinical decision making and preference assessment for individuals with
      intellectual and developmental disabilities.
AB  - Individuals with intellectual or developmental disabilities are able to reliably
      express their likes and dislikes through direct preference assessment. Preferred
      items tend to function as rewards and can therefore be used to facilitate the
      acquisition of new skills and promote task engagement. A number of preference
      assessment methods are available and selecting the appropriate method is crucial
      to provide reliable and meaningful results. The authors conducted a systematic
      review of the preference assessment literature, and developed an evidence
      informed, decision-making model to guide practitioners in the selection of
      preference assessment methods for a given assessment scenario. The proposed
      decision-making model could be a useful tool to increase the usability and uptake
      of preference assessment methodology in applied settings.

PMID- 24679352
TI  - Child behavior problems and parental well-being in families of children with
      autism: the mediating role of mindfulness and acceptance.
AB  - Few research studies have explored how the level of a child's behavior problems
      leads to psychological distress in parents of children with autism. The authors
      explored whether psychological acceptance and mindfulness mediated this
      relationship between child behavior and parental distress. Seventy-one mothers
      and 39 fathers of children with autism participated, by reporting on their own
      positive and negative psychological well-being and their child's behavior
      problems. Psychological acceptance was found to act as a mediator variable for
      maternal anxiety, depression, and stress, and for paternal depression. General
      mindfulness and mindful parenting had significant mediation effects for maternal
      anxiety, depression, and stress. These results contribute to evidence that
      mindfulness and acceptance may be important parental psychological processes,
      with implications for parent support.

PMID- 24679353
TI  - Coping and psychological health of aging parents of adult children with
      developmental disabilities.
AB  - Among aging parents (mean age  =  65, N  =  139) of adults with developmental
      disabilities, we examined the effectiveness of multiple forms of coping with
      caregiver burden. As expected, accommodative strategies of adapting to stress
      (secondary engagement), used frequently in later life, buffered the impact of
      caregiver burden, whereas disengagement and distraction strategies exacerbated
      the effects of burden on depression symptoms. Most effects were similar for
      mothers and fathers, and all coping strategies, including active strategies to
      reduce stress (primary engagement), had greater effects for the parents with co
      resident children. Vulnerability to caregiver burden was greatest when the aging
      parents with co-resident children used disengagement and distraction coping, but
      those who used engagement coping were resilient.

PMID- 24679357
TI  - Economics of fertility in high-yielding dairy cows on confined TMR systems.
AB  - The objective of this review paper was to summarise the latest findings in dairy
      cattle reproductive economics with an emphasis on high yielding, confined total
      mixed ration systems. The economic gain increases as the reproductive efficiency
      improves. These increments follow the law of diminishing returns, but are still
      positive even at high reproductive performance. Reproductive improvement results
      in higher milk productivity and, therefore, higher milk income over feed cost,
      more calf sales and lower culling and breeding expenses. Most high-yielding herds
      in the United States use a combination of timed artificial insemination (TAI) and
      oestrous detection (OD) reproductive programme. The ratio of achievable
      pregnancies between OD and TAI determines the economic value difference between
      both and their combinations. Nonetheless, complex interactions between
      reproductive programme, herd relative milk yield, and type of reproductive
      programme are reported. For example, higher herd relative milk yield would favour
      programme relying more on TAI. In addition, improved reproductive efficiency
      produces extra replacements. The availability of additional replacements could
      allow more aggressive culling policies (e.g. less services for non-pregnant cows)
      to balance on-farm supply and demand of replacements. Balancing heifer
      replacement availability in an efficient reproductive programme brings additional
      economic benefits. New technologies such as the use of earlier chemical tests for
      pregnancy diagnosis could be economically effective depending on the goals and
      characteristics of the farm. Opportunities for individual cow reproductive
      management within defined reproductive programme exist. These decisions would be
      based on economic metrics derived from the value of a cow such as the value of a
      new pregnancy, the cost of a pregnancy loss, or the cost of an extra day open. 

PMID- 24679358
TI  - Lactating and non-lactating rats differ in sensitivity to HgCl(2): Protective
      effect of ZnCl(2).
AB  - This work investigated zinc (Zn) and mercury (Hg) effects on oxidative
      parameters, markers of toxicity and metal levels in different tissues from non
      lactating rats (NLR) and lactating rats (LR). Adult NLR and LR received ZnCl2
      (27mg/kg) or saline (0.9%) subcutaneously and after 24h they received HgCl2
      (5mg/kg) or saline (0.9%). Twenty four hours later, they were sacrificed and the
      preparation of biological material and biochemical analyses were performed. With
      respect to oxidative parameters, Hg exposure decreased kidney total SH levels
      from NLR and LR and hepatic catalase activity (not statistically significant) in
      NLR. Zinc pre-treatment partly prevented the decrease of kidney total SH levels
      in LR. Zinc per se increased hepatic non-protein SH levels of NLR and LR.
      Regarding toxicity markers, Hg exposure inhibited the delta-aminolevulinic acid
      dehydratase (delta-ALA-D) activity from kidney and liver of NLR, inhibited serum
      alanine aminotransferase (ALT) activity of LR and increased serum creatinine and
      urea levels of NLR and LR. Zinc pre-exposure prevented the enzymatic alterations
      caused by Hg. NLR and LR Hg exposed presented accumulation of mercury in the
      kidney, liver, blood and urine. Zinc pre-treatment prevented this accumulation
      partly in NLR liver and blood and completely in LR kidney and liver. These
      results show that NLR and LR are differently sensitive to HgCl2 and that ZnCl2
      showed a promising effect against Hg toxicity. 

PMID- 24679359
TI  - Abdominosacral resection: long-term outcome in 86 patients with locally advanced
      or locally recurrent rectal cancer.
AB  - AIMS: The purpose of this study is to evaluate the outcome of abdominosacral
      resections (ASR) in patients with locally advanced or recurrent rectal cancer.
      METHODS: From 1994 until 2012 patients with locally advanced rectal cancer (LARC)
      and locally recurrent rectal cancer (LRRC) underwent a curative ASR and were
      enrolled in a database. The postoperative complication rates, predictive factors
      on oncological outcome and survival rates were registered. RESULTS: Seventy-two
      patients with LRRC (mean age 63; 44 male, 28 female) and 14 patients with LARC
      (mean age 65; 6 male, 8 female) underwent ASR. R0 resection was achieved in 37
      patients with LRRC and 11 patients with LARC. Twenty-seven patients underwent an
      R1 resection (3 in the LARC group). Eight patients had an R2 resection, compared
      to no patients in the LARC group. In respectively 26 and 1 patients of the LRRC
      and LARC groups a grade 3 or 4 complication occurred and the 30-days mortality
      rate was respectively 3% and 7%. The 5-years overall survival was 28% and 24%
      respectively. CONCLUSION: En bloc radical resection remains the primary goal in
      the treatment of dorsally located (recurrent) rectal cancer. After thorough
      patient selection, ASR is a safe procedure to perform, shows acceptable morbidity
      rates and leads to a good oncological outcome.

PMID- 24679360
TI  - Indirect decompression for a prior severe C1-2 dislocation causing progressive
      quadriparesis.
AB  - Combined anterior and posterior surgery is frequently chosen for the treatment of
      prior, severe C1-2 dislocations that occurred during early childhood because of
      the difficulty in achieving reduction and satisfactory decompression. The authors
      treated a prior, severe C1-2 dislocation that was causing progressive
      quadriparesis. The patient was a 14-year-old boy who had suffered a C1-2 fracture
      dislocation at 3 years of age and had been treated with a Minerva body jacket
      cast. The treatment involved posterior C1-2 segmental screw fixation, without
      direct bone decompression or additional surgery. Satisfactory neural
      decompression was achieved with the techniques used, and complete bone union was
      confirmed. The patient showed satisfactory neurological recovery at the 5-year
      follow-up assessment. 

PMID- 24679361
TI  - Commentary on 'Ultrasound-guided intralesional diode laser treatment of
      congenital extratruncular venous malformations: mid-term results'.

PMID- 24679362
TI  - The effect of two mobilization techniques on dorsiflexion in people with chronic
      ankle instability.
AB  - OBJECTIVE: To compare the effect of two manual therapy techniques, mobilization
      with movement (WB-MWM) and talocrural manipulation (HVLA), for the improvement of
      ankle dorsiflexion in people with chronic ankle instability (CAI) over 48 h.
      DESIGN: Randomized controlled clinical trial. SETTING: University research
      laboratory. PARTICIPANTS: Fifty-two participants (mean +/- SD age, 20.7 +/- 3.4
      years) with CAI were randomized to WB-MWM (n = 18), HVLA (n = 19) or placebo
      group (n = 15). MAIN OUTCOME MEASURES: Weight-bearing ankle dorsiflexion measured
      with the weight-bearing lunge. Measurements were obtained prior to intervention,
      immediately after intervention, and 10 min, 24 h and 48 h post-intervention.
      RESULTS: There was a significant effect * time (F4,192 = 20.65; P < 0.001) and a
      significant time * group interactions (F8,192 = 6.34; P < 0.001). Post hoc
      analysis showed a significant increase of ankle dorsiflexion in both WB-MWM and
      HVLA groups with respect to the placebo group with no differences between both
      active treatment groups. CONCLUSION: A single application of WB-MWM or HVLA
      manual technique improves ankle dorsiflexion in people with CAI, and the effects
      persist for at least two days. Both techniques have similar effectiveness for
      improving ankle dorsiflexion although WB-MWM demonstrated greater effect sizes.

PMID- 24679364
TI  - Nicorandil: ulcer and location.

PMID- 24679363
TI  - Dynamic analysis of platelet deposition to resolve platelet adhesion receptor
      activity in whole blood at arterial shear rate.
AB  - Platelet activation is traditionally quantified using turbidimetric aggregometry,
      which reflects integrin alphaIIbbeta3 activity, an important determinant of
      platelet function during pathophysiological thrombus formation. However,
      aggregometry does not recreate the shear conditions prevailing during thrombosis
      in vivo. Here we describe novel whole-frame analysis of real-time video
      microscopy to quantify platelet adhesion receptor activity under shear in
      parallel-plate flow chambers. We demonstrate that the rate of change of surface
      coverage (designated Platelet Population Mobility, PM) quantifies platelet
      mobility. On collagen, PM falls exponentially to a low level, corresponding to
      firm platelet adhesion, while on other substrates, PM remains high. Different
      receptor-specific thrombogenic surfaces reveal that the PM time constant reflects
      real-time changes in integrins alphaIIbbeta3 and alpha2beta1 activity. This
      ensemble kinetic analysis has the potential to provide valuable diagnostic
      information about platelet thrombus formation with both academic and clinical
      applications. 

PMID- 24679365
TI  - Time spent on daytime direct care activities by personal carers in two Australian
      residential aged care facilities: a time-motion study.
AB  - OBJECTIVE: To examine the time, frequency and duration of each direct care
      activity conducted by personal carers in Australian residential aged care homes.
      METHODS: A time-motion study was conducted to observe 46 personal carers at two
      high-care houses in two facilities (14 days at Site 1 and 16 days at Site 2).
      Twenty-three direct care activities were classified into eight categories for
      analysis. RESULTS: Overall, a personal carer spent approximately 45% of their
      time on direct care, corresponding to 3.5h in an 8-h daytime shift. The two sites
      had similar ratios of personal carers to residents, and each resident received 30
      min of direct care. No significant differences between the two sites were found
      in the time spent on oral communication, personal hygiene and continence
      activities. Personal carers at Site 1 spent significantly less time on toileting
      and mobility activities than those at Site 2, but more time on lunch activity.
      Although oral communication took the longest time (2h), it occurred concurrently
      with other activities (e.g. dressing) for 1.5h. CONCLUSIONS: The findings provide
      information that may assist decision makers in managing the operation of high
      care residential aged care facilities, such as planning for task allocation and
      staffing. What is known about the topic? Overall, 30%-45% of the care staff's
      time is spent on direct care in residential aged care facilities. What does this
      paper add? This paper adds knowledge about how much time is required to conduct
      each direct care activity and the frequency and duration of conducting these
      activities to meet residents' day-to-day care needs in two high-care houses in
      two aged care facilities. What are the implications for practitioners? On
      average, a resident with high-care needs requires 30 min direct care. There may
      exist a basic minimum desirable ratio of personal carers to residents in high
      care facilities. Residents' toileting needs are high after meals. Communication
      with residents represents an essential role in providing care.

PMID- 24679367
TI  - Cryotherapy with dynamic intermittent compression for analgesia after anterior
      cruciate ligament reconstruction. Preliminary study.
AB  - BACKGROUND: Cryotherapy is a useful adjunctive analgesic measure in patients with
      postoperative pain following anterior cruciate ligament (ACL) surgery. Either
      static permanent compression or dynamic intermittent compression can be added to
      increase the analgesic effect of cryotherapy. Our objective was to compare the
      efficacy of these two compression modalities combined with cryotherapy in
      relieving postoperative pain and restoring range of knee motion after ligament
      reconstruction surgery. HYPOTHESIS: When combined with cryotherapy, a dynamic and
      intermittent compression is associated with decreased analgesic drug
      requirements, less postoperative pain, and better range of knee motion compared
      to static compression. MATERIALS AND METHODS: We conducted a case-control study
      of consecutive patients who underwent anterior cruciate ligament reconstruction
      at a single institution over a 3-month period. Both groups received the same
      analgesic drug protocol. One group was managed with cryotherapy and dynamic
      intermittent compression (Game Ready((r))) and the other with cryotherapy and
      static compression (IceBand((r))). RESULTS: Of 39 patients, 20 received dynamic
      and 19 static compression. In the post-anaesthesia recovery unit, the mean visual
      analogue scale (VAS) pain score was 2.4 (range, 0-6) with dynamic compression and
      2.7 (0-7) with static compression (P=0.3); corresponding values were 1.85 (0-9)
      vs. 3 (0-8) (P=0.16) after 6 hours and 0.6 (0-3) vs. 1.14 (0-3) (P=0.12) at
      discharge. The cumulative mean tramadol dose per patient was 57.5mg (0-200mg)
      with dynamic compression and 128.6 mg (0-250 mg) with static compression
      (P=0.023); corresponding values for morphine were 0mg vs. 1.14 mg (0-8 mg)
      (P<0.05). Mean range of knee flexion at discharge was 90.5 degrees  (80 degrees 
      100 degrees ) with dynamic compression and 84.5 degrees  (75 degrees -90 degrees
      ) with static compression (P=0.0015). CONCLUSION: Dynamic intermittent
      compression combined with cryotherapy decreases analgesic drug requirements after
      ACL reconstruction and improves the postoperative recovery of range of knee
      motion. LEVEL OF EVIDENCE: Level III, case-control study.

PMID- 24679366
TI  - Proprioceptive function after isolated single-bundle posterior cruciate ligament
      reconstruction with remnant preservation for chronic posterior cruciate ligament
      injuries.
AB  - INTRODUCTION: Posterior cruciate ligament (PCL) reconstruction using the remnant
      preserving technique may contribute to improved postoperative posterior
      stability, graft healing, and proprioception recovery. Although there have been
      several reports on remnant preserving PCL reconstruction, no study has yet
      evaluated the proprioceptive functions before and after PCL reconstruction with
      remnant preservation. The purpose of this study is to retrospectively evaluate
      the clinical outcomes and proprioceptive function after isolated single-bundle
      PCL reconstruction with remnant preservation for chronic PCL injuries.
      HYPOTHESIS: Isolated single-bundle PCL reconstruction with remnant preservation
      surgery for chronic PCL injuries provides satisfactory clinical outcomes and good
      recovery of the proprioceptive function. METHODS: Nineteen patients who had
      undergone isolated single-bundle PCL reconstruction with remnant preservation for
      chronic PCL injuries were followed up for more than 2 years. The posterior laxity
      was measured by the gravity sag view, stress radiography and the KT-2000 knee
      arthrometer. The proprioceptive function was defined as the threshold to detect
      passive motion (TTDPM). RESULTS: The average Lysholm score significantly improved
      from 63.7+/-13.2 preoperatively to 94.4+/-4.6 at final follow-up. The
      postoperative posterior laxity significantly improved. Regarding TTDPM, there
      were no significant differences between the preoperative score and the score at
      every given time point, regardless of the starting angles and the moving
      directions of the knees. CONCLUSIONS: The proprioceptive function, defined as
      TTDPM, is maintained after single-bundle PCL reconstruction with remnant
      preservation, and the postoperative clinical scores and posterior laxity
      significantly improve. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24679368
TI  - Percutaneous CT-guided radiofrequency thermocoagulation in the treatment of
      osteoid osteoma: a 87 patient series.
AB  - INTRODUCTION: Osteoid osteoma is a painful, benign bone tumor that mainly affects
      young people. Thermocoagulation is one of the recommended percutaneous treatment
      methods. This study sought to assess its efficacy and identify risk factors for
      osteoma recurrence. METHODS: Results were analyzed retrospectively for a group of
      87 patients treated by thermocoagulation between 2002 and 2011. The recurrence
      rate was calculated and analyzed relative to patient and tumor characteristics.
      The treatment efficacy was determined and methods to prevent complications were
      analyzed. RESULTS: The mean follow-up time was 34 months. The average patient age
      was 23 years. There were seven complications including three patients with
      delayed wound healing, mainly at tibial sites. The recurrence rate was 10.4%. The
      success rate for first-line treatment was 89.6% and it was 97.5% for second-line
      treatment. Analysis of patient characteristics and tumor locations revealed no
      risk factors for recurrence. CONCLUSION: Percutaneous thermocoagulation is a
      reliable and effective technique that provides fast, long-lasting pain relief.
      However recurrence can occur even after the nidus is completely resected. These
      recurrences can be effectively managed by repeat treatment. Recent technical
      improvements have reduced the risk of thermocoagulation-related complications.
      LEVEL OF EVIDENCE: IV.

PMID- 24679369
TI  - Percutaneous quadriceps tendon pie-crusting release of extension contracture of
      the knee.
AB  - To release extension contracture of the knee, the authors used a minimally
      invasive technique: percutaneous quadriceps tendon pie-crusting release.
      Percutaneous pie-crusting release was performed using an 18-gauge needle to
      puncture the stiff fibrous band of the distal and lateral quadriceps tendon under
      maximum knee flexion. Quadriceps contracture was gradually released by multiple
      needle punctures. A knee brace was prescribed for one week and knee flexion
      exercises were performed on the first postoperative day. This technique was
      performed in seven post-traumatic stiff knees and five stiff total knee
      arthroplasties. Mean maximum flexion increased from 37 degrees  preoperatively to
      50 degrees  after arthrolysis and 107(o) after pie-crusting. At a mean follow-up
      of eight months, mean maximum flexion was 103 degrees . There were no major
      complications. The technique of quadriceps tendon pie-crusting release is a
      simple, minimally invasive and effective treatment for knee extension
      contracture.

PMID- 24679370
TI  - Arthroscopic treatment of an intra-articular hemangioma in the posterior
      compartment of the knee.
AB  - We report the case of a 37-year-old patient presenting with knee pain and
      recurrent effusion without instability due to an intra-articular hemangioma in
      the posterior compartment of the knee. MRI showed features suggesting a diagnosis
      of hemangioma. Arthroscopic excision of the tumor was performed and the diagnosis
      was confirmed histologically. There was no recurrence after 5 years of follow-up.

PMID- 24679371
TI  - Comparison of modified Hackethal bundle nailing versus anterograde nailing for
      fixation of surgical neck fractures of the humerus: retrospective study of 105
      cases.
AB  - INTRODUCTION: Intramedullary fixation of displaced surgical neck fractures of the
      humerus can be performed either by retrograde pinning or anterograde nailing. The
      goal of the current study was to compare the postoperative reduction and
      stability obtained with these two techniques. HYPOTHESIS: Intramedullary nailing
      will provide the best reduction and stabilization of these fractures. PATIENTS
      AND METHODS: This was a multicenter retrospective study that included patients
      with sub-tuberosity fractures with or without greater tuberosity fragment. These
      patients were treated either by retrograde Hackethal type pinning (group 1) or
      Telegraph anterograde nailing (group 2). To be included, patients needed to have
      A/P and lateral X-rays that had been taken before the surgery, immediately post
      operative, between four and six weeks post-operative, and at the last follow-up.
      The outcomes were head angulation, translation and greater tuberosity position.
      RESULTS: One hundred and five patients (40 retrograde pinning and 65 anterograde
      nailing) with an average age of 69 years (18-97 years) were included. The pre
      operative fracture displacement was similar between the two groups. After the
      surgery, the A/P head angulation had been corrected in 72.5% of patients in group
      1 and 84% in group 2 (no significant difference). Translation was still present
      in 17.5% of patients in group 1 and 1.5% in group 2 (P<0.05). At the last follow
      up, union was achieved without residual angulation on lateral X-rays in 71% of
      patients in group 1 and 88% in group 2 (P<0.05). The fractures had healed with
      residual translation is 19.5% of patients in group 1 and 3% in group 2 (P<0.05).
      DISCUSSION AND CONCLUSION: In cases of displaced surgical neck fractures with or
      without a greater tuberosity fragment, anterograde nailing provides better
      reduction and stability than retrograde pinning. However, fixation of the greater
      tuberosity fragment must be improved. LEVEL OF EVIDENCE: IV (retrospective
      comparative study).

PMID- 24679372
TI  - MR imaging-guided vacuum-assisted breast biopsy: reduction of false-negative
      biopsies by short-term control MRI 24-48 h after biopsy.
AB  - AIM: To evaluate whether another contrast-enhanced (CE) magnetic resonance
      imaging (MRI) examination 24-48 h after MRI-guided vacuum-assisted breast biopsy
      (MRI-VAB) can reduce the rate of false-negative cases. MATERIALS AND METHODS: The
      study included 252 patients who underwent MRI-VAB for the clarification of 299
      lesions. The success of MRI-VAB was assessed at interventional MRI and another CE
      MRI 24-48 h after the intervention. In cases of successful MRI-VAB (complete or
      partial lesion removal) and benign histological results, follow-up breast MRI was
      performed. In cases of unsuccessful biopsy (unchanged lesion), tissue sampling
      was repeated. False-negative cases were calculated to assess the diagnostic value
      of MRI follow-up within 2 days after intervention. RESULTS: Ninety-eight
      malignant (32.8%) and 201 (67.2%) benign lesions were diagnosed using MRI-VAB. At
      immediate unenhanced control MRI, all lesions were assessed as successfully
      biopsied. In 18 benign cases (6%), CE MRI after 24-48 h showed an unsuccessful
      intervention. Further tissue sampling revealed another 13 cancers in these
      patients. This results in a false-negative rate of 11.7%. Follow-up MRI of the
      benign lesions presented no further malignancy. CONCLUSIONS: MRI-VAB with
      immediate unenhanced control offers a success rate of 94%. The rate of false
      negative biopsies (11.7%) could be reduced to zero by using short-term follow-up
      MRI. Therefore, a further CE breast MRI 24-48 h after benign MRI-VAB to eliminate
      missed cancers is recommended.

PMID- 24679373
TI  - Test-retest reliability and comparability of paper and computer questionnaires
      for the Finnish version of the Tampa Scale of Kinesiophobia.
AB  - OBJECTIVES: To estimate the internal consistency, test-retest reliability and
      comparability of paper and computer versions of the Finnish version of the Tampa
      Scale of Kinesiophobia (TSK-FIN) among patients with chronic pain. In addition,
      patients' personal experiences of completing both versions of the TSK-FIN and
      preferences between these two methods of data collection were studied. DESIGN:
      Test-retest reliability study. Paper and computer versions of the TSK-FIN were
      completed twice on two consecutive days. PARTICIPANTS: The sample comprised 94
      consecutive patients with chronic musculoskeletal pain participating in a pain
      management or individual rehabilitation programme. The group rehabilitation
      design consisted of physical and functional exercises, evaluation of the social
      situation, psychological assessment of pain-related stress factors, and personal
      pain management training in order to regain overall function and mitigate the
      inconvenience of pain and fear-avoidance behaviour. RESULTS: The mean TSK-FIN
      score was 37.1 [standard deviation (SD) 8.1] for the computer version and 35.3
      (SD 7.9) for the paper version. The mean difference between the two versions was
      1.9 (95% confidence interval 0.8 to 2.9). Test-retest reliability was 0.89 for
      the paper version and 0.88 for the computer version. Internal consistency was
      considered to be good for both versions. The intraclass correlation coefficient
      for comparability was 0.77 (95% confidence interval 0.66 to 0.85), indicating
      substantial reliability between the two methods. CONCLUSION: Both versions of the
      TSK-FIN demonstrated substantial intertest reliability, good test-retest
      reliability, good internal consistency and acceptable limits of agreement,
      suggesting their suitability for clinical use. However, subjects tended to score
      higher when using the computer version. As such, in an ideal situation, data
      should be collected in a similar manner throughout the course of rehabilitation
      or clinical research.

PMID- 24679374
TI  - Assessment and management of risk factors for the prevention of lifestyle-related
      disease: a cross-sectional survey of current activities, barriers and perceived
      training needs of primary care physiotherapists in the Republic of Ireland.
AB  - OBJECTIVE: To provide a snapshot of current activities, barriers and perceived
      training needs for the assessment and management of behavioural risk factors in
      physiotherapy practice in primary care settings in the Republic of Ireland.
      DESIGN: Cross-sectional survey of primary care physiotherapists. METHOD: Two
      hundred and twenty primary care physiotherapists were invited to participate.
      Each received a questionnaire, consisting of 23 questions, within five key
      sections. Its main focus was the risk factor management practices of
      physiotherapists. Descriptive statistics and frequencies were used to analyse the
      data. RESULTS: A response rate of 74% (163/220) was achieved. Level of physical
      activity was the most common risk factor assessed at initial and follow-up visits
      (78%, 127/163), followed by dietary status (55%, 90/163). Few respondents
      included smoking status and alcohol consumption in their assessment; however, the
      majority considered them as risk factors that should be addressed. The main
      reasons why smoking status and alcohol consumption were not assessed were lack of
      time, limited knowledge and expertise, not traditionally viewed as the
      physiotherapist's role, and patient's lack of interest in changing their
      unhealthy behaviour. CONCLUSION: The findings highlight an untapped potential in
      relation to physiotherapists addressing lifestyle-related risk factors. A number
      of strategies are required to improve the systematic assessment and management of
      these risk factors.

PMID- 24679376
TI  - [Future prospects for hepatitis C treatment: without interferon and ribavirin?].
AB  - The hepatitis C virus is an important health problem worldwide. Currently, the
      standard treatment of genotype 1 chronic hepatitis C is the combination of
      pegylated interferon, ribavirin and a first-generation protease inhibitor:
      telaprevir or boceprevir. This triple therapy has improved the efficacy of
      treatment but has also increased regimen complexity, costs, and the number of
      adverse effects (mainly hematological and cutaneous). Unfortunately, viral
      response rates are still suboptimal in patients with cirrhosis, particularly
      those with a prior null response. Moreover, studies carried out in clinical
      practice have shown that the presence of advanced fibrosis confers a high risk of
      developing severe adverse effects during treatment (infection, decompensation and
      even death). It is therefore essential to select candidates for triple therapy
      according to their risk of complications and possibilities for cure. In this
      scenario, interferon (and ribavirin)-free combinations are very safe and well
      tolerated first-line treatments. This review describes the current treatment of
      hepatitis C as well as the latest results of studies combining distinct direct
      antiviral agents without interferon. It is hoped that these drugs will be
      available shortly, although their cost may be high. Consequently, it is essential
      to identify those patients who could derive the greatest benefit from these
      treatments. 

PMID- 24679375
TI  - [Late gastric metastasis from cutaneous melanoma].

PMID- 24679377
TI  - [An unusual cause of hemobilia: hepatic artery pseudoaneurysm after endoscopic
      retrograde cholangiopancreatography].

PMID- 24679378
TI  - [Implementation and evaluation of a blended learning course on gastroesophageal
      reflux disease for physicians in Latin America].
AB  - Integrating evidence-based clinical practice guidelines on gastroesophageal
      reflux disease into medical practice is of prime importance in Latin America,
      given its high prevalence in this region. The aim of this project was to
      implement and assess an educational intervention on gastroesophageal reflux
      disease, aimed at primary care physicians in Latin America, with contents based
      on current clinical guidelines. The course included initial activities, whether
      face-to-face or through distance learning, and a 2-month period of Internet study
      and interaction. A pilot test was carried out in Uruguay, which was then repeated
      in 5 countries (Mexico, Colombia, Venezuela, Argentina and again in Uruguay). A
      global template was designed, which was then adapted to each of the countries:
      this was done with the participation of local institutions and leaders. Local
      credits were given for recertification. Participation was free. Of 3,110
      physicians invited to participate, 1,143 (36.8%) started the course. Of these,
      587 (51.4%) accessed at least half the contents of the course and 785 (68.7%)
      took part in the clinical discussions. A total of 338 (29.6%) completed all the
      requirements of the course and received a certificate. Among physicians who took
      both the pre- and post-intervention knowledge tests, scores improved from 60 to
      80% (P<.001). Ninety-two percent of planned changes in clinical practice were
      related to the pedagogic aims of the course. In conclusion, a multifaceted, 2
      phase continuing education course was successfully imparted in Latin America,
      with an overall design that was adapted to each country. Determination of
      specific needs and the participation of national experts were fundamental to the
      success of the course. 

PMID- 24679379
TI  - Recent advances to address European Union Health Security from cross border
      chemical health threats.
AB  - The European Union (EU) Decision (1082/2013/EU) on serious cross border threats
      to health was adopted by the European Parliament in November 2013, in recognition
      of the need to strengthen the capacity of Member States to coordinate the public
      health response to cross border threats, whether from biological, chemical,
      environmental events or events which have an unknown origin. Although mechanisms
      have been in place for years for reporting cross border health threats from
      communicable diseases, this has not been the case for incidents involving
      chemicals and/or environmental events. A variety of collaborative EU projects
      have been funded over the past 10 years through the Health Programme to address
      gaps in knowledge on health security and to improve resilience and response to
      major incidents involving chemicals. This paper looks at the EU Health Programme
      that underpins recent research activities to address gaps in resilience,
      planning, responding to and recovering from a cross border chemical incident. It
      also looks at how the outputs from the research programme will contribute to
      improving public health management of transnational incidents that have the
      potential to overwhelm national capabilities, putting this into context with the
      new requirements as the Decision on serious cross border threats to health as
      well as highlighting areas for future development.

PMID- 24679380
TI  - Monitoring lead in hair of children and adolescents of Alcala de Henares, Spain.
      A study by gender and residential areas.
AB  - In recent years there has been an increased interest from the European Union (EU)
      in the development of large Human Bio-monitoring (HBM) studies across Europe,
      especially biomonitoring toxic metals. In Spain, most studies using hair as a
      biomarker have been conducted to determine occupational or industrial exposures,
      and have involved adult populations. Few studies have involved adolescents and
      children, despite these groups being sensitive to environmental contamination and
      pollutants. Therefore, the objective of the present study was to determine the
      degree of lead exposure in children and adolescents residing in Alcala de
      Henares, Spain. Lead poisoning is the number one toxicological threat in the
      environment. So, lead (Pb) was selected as it is a persistent environmental
      contaminant, is measureable and is also a neurotoxin that can affect brain
      development. The city of Alcala de Henares was divided into four zones to
      determine the influence of residence area on Pb levels. A range of other
      variables including age and gender were also considered within the study. The
      study comprised 115 children (6-9 years old) and 96 adolescents (13-16 years
      old). There was a significant difference between the levels of Pb in the hair of
      adolescents, for different gender and area of residence (p<0.001 and p<0.01
      respectively). There was no significant difference in the Pb levels in hair of
      children, for different gender or area of the city. The levels of Pb were
      significantly (p<0.001) elevated in children compared to adolescents (1.48 vs.
      0.70 MUg/g), and there was a significant difference in Pb levels in male and
      female adolescent hair (0.53 vs. 0.77 MUg/g) (p<0.001). The association observed
      between areas of residence and the Pb level in hair of the adolescent group could
      be mainly attributed to dietary habits and/or socioeconomic status.

PMID- 24679381
TI  - A novel hypothesis comprehensively explains shock, heart failure and aerobic
      exhaustion through an assumed central physiological control of the momentary
      cardiovascular performance reserve.
AB  - BACKGROUND: Heart failure (HF) and shock are incomprehensively understood,
      inconclusively defined and lack a single conclusive test. The proceedings that
      preceded and triggered clinical manifestations are occult. The relationships in
      between different shock and HF types and between each HF type and its matched
      shock are poorly understood. THE ASSUMED HYPOTHESIS: We suggest that HF and shock
      are attributed to a momentary cardiovascular performance reserve - "the reserve".
      The reserve is controlled through an assumed central physiological mechanism that
      continuously detects and responds accordingly--"the reserve control". The assumed
      reserve is maximal at rest, and decreases with aerobic activity. When it
      decreases to a given threshold the reserve control alerts by induces
      manifestations of dyspnea and fatigue enforcing activity decrease, follow which
      the manifestations dissolve. HF is a condition of low reserve at baseline; hence,
      fatigue and dyspnea are frequently experienced following mild activity. Shock is
      assumed to occur when the cardiovascular reserve deteriorates below a sustainable
      limit where the reserve control induces a salvage-sacrifice response, preserving
      vital organ perfusion while impairing microcirculation effective perfusion in non
      vital organ in which it causes cellular hypoxia followed by the familiar
      devastating cascade of events seen in shock. DISCUSSION AND CONCLUSIONS: The
      hereby hypothesis may comprehensively explain the heart failure - shock puzzle as
      no alternative theory had ever succeeded. It provides the missing link between
      the different types of HF as of shock and in between. The hypothesis poses a
      great prove challenge but opens new research and clinical possibilities.

PMID- 24679382
TI  - Dietary patterns are associated with the prevalence of elevated depressive
      symptoms and the risk of getting a hospital discharge diagnosis of depression in
      middle-aged or older Finnish men.
AB  - BACKGROUND: Previous studies assessing the role of dietary factors in depression
      have mainly focused on nutrients, while the association between dietary patterns
      and depression is less studied. OBJECTIVE: The aim was to assess the role of
      dietary patterns in depression in both cross-sectional and prospective analyses.
      DESIGN: The study population consisted of 1003 Finnish middle-aged or older men
      from the Kuopio Ischemic Heart Disease Risk Factor Study. Food consumption was
      assessed by food frequency questionnaire in 1991-1993 and dietary patterns from
      25 predefined food groups were extracted by factor analysis. Depressive symptoms
      were assessed with the self-administered Human Population Laboratory Depression
      Scale, cut-off point of five or more indicating elevated depressive symptoms.
      RESULTS: Altogether 72 (7.2%) subjects had elevated depressive symptoms. Three
      dietary patterns were identified: "prudent", "Western" and "mixed". In cross
      sectional analysis, after adjustments for age, examination year, BMI, smoking,
      alcohol consumption, education, marital status, leisure-time physical activity,
      history of mental illness and cardiovascular disease the prudent dietary pattern
      was associated with a 25% lower prevalence of elevated depressive symptoms (OR:
      0.75; 95% CI: 0.57, 0.99; P=0.036), whereas the Western dietary pattern was
      associated with increased prevalence of elevated depressive symptoms (OR: 1.41;
      95% CI: 1.08, 1.84; P=0.011). In the prospective analysis (16.5 follow-up years),
      the prudent dietary pattern was inversely associated with the risk of getting a
      hospital discharge diagnosis of depression (HR: 0.66; 95% CI 0.47, 0.93;
      P=0.018). CONCLUSIONS: Adherence to healthy dietary pattern is associated with
      lower risk of getting a hospital discharge diagnosis of depression.

PMID- 24679383
TI  - Caregiver burden, family accommodation, health, and well-being in relatives of
      individuals with hoarding disorder.
AB  - BACKGROUND: Hoarding Disorder (HD), a new diagnostic entity in DSM-5, is
      associated with substantial functional impairment and family frustration but data
      from well-characterized samples is lacking. METHOD: Participants were 37
      individuals meeting DSM-5 criteria for HD, 55 relatives of individuals meeting
      criteria for HD, and comparison groups of 51 self-identified collectors and 25
      relatives of collectors. All participants completed a clinician-administered
      diagnostic interview for HD and an online battery of standardized measures of
      health, well-being, and impairment. RESULTS: Substantial functional impairment
      was found for both HD individuals and their relatives. HD relatives reported
      significantly greater carer burden and accommodation of hoarding behaviors than
      relatives of collectors. Perceived level of squalor, co-habiting with, and
      increasing age of the HD individual were significant predictors of carer burden
      and functional impairment in the relatives. LIMITATIONS: The use of self
      identified HD individuals may have produced a bias towards participants with
      relatively good insight. Subjective biases in self-reported symptoms cannot be
      ruled out, although the use of informant-report data provided some independent
      validation. CONCLUSIONS: HD is associated with substantial functional impairment
      for both sufferers and their relatives. The level of carer burden experienced by
      HD relatives was comparable to or greater than that reported in the literature by
      relatives of individuals with dementia. The findings indicate that relatives of
      individuals with HD may benefit from increased support and suggest that it may be
      beneficial to involve family members in the treatment of HD.

PMID- 24679384
TI  - Improving the detection and prediction of suicidal behavior among military
      personnel by measuring suicidal beliefs: an evaluation of the Suicide Cognitions
      Scale.
AB  - BACKGROUND: Newer approaches for understanding suicidal behavior suggest the
      assessment of suicide-specific beliefs and cognitions may improve the detection
      and prediction of suicidal thoughts and behaviors. The Suicide Cognitions Scale
      (SCS) was developed to measure suicide-specific beliefs, but it has not been
      tested in a military setting. METHODS: Data were analyzed from two separate
      studies conducted at three military mental health clinics (one U.S. Army, two
      U.S. Air Force). Participants included 175 active duty Army personnel with acute
      suicidal ideation and/or a recent suicide attempt referred for a treatment study
      (Sample 1) and 151 active duty Air Force personnel receiving routine outpatient
      mental health care (Sample 2). In both samples, participants completed self
      report measures and clinician-administered interviews. Follow-up suicide attempts
      were assessed via clinician-administered interview for Sample 1. Statistical
      analyses included confirmatory factor analysis, between-group comparisons by
      history of suicidality, and generalized regression modeling. RESULTS: Two latent
      factors were confirmed for the SCS: Unloveability and Unbearability. Each
      demonstrated good internal consistency, convergent validity, and divergent
      validity. Both scales significantly predicted current suicidal ideation (betas
      >0.316, ps <0.002) and significantly differentiated suicide attempts from
      nonsuicidal self-injury and control groups (F(6, 286)=9.801, p<0.001). Both
      scales significantly predicted future suicide attempts (AORs>1.07, ps <0.050)
      better than other risk factors. LIMITATIONS: Self-report methodology, small
      sample sizes, predominantly male samples. CONCLUSIONS: The SCS is a reliable and
      valid measure that predicts suicidal ideation and suicide attempts among military
      personnel better than other well-established risk factors.

PMID- 24679385
TI  - Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression
      and PON1 Q192R gene polymorphism-smoking interactions differentially predict the
      odds of major depression and bipolar disorder.
AB  - BACKGROUND: Major depression and bipolar disorder are accompanied by the
      activation of immune-inflammatory and Oxidative and Nitrosative Stress (O&NS)
      pathways and lowered levels of antioxidants. Paraoxonase (PON)1 (EC 3.1.8.1) is
      an antioxidant bound to High Density Lipoprotein (HDL). Polymorphisms in the PON1
      Q192R coding sequence determine three functional genotypes, i.e. 192QQ, 192QR and
      192RR. AIMS: This study was carried out to delineate the associations of plasma
      PON1 activity and functional PON1 Q192R genotypes in major depression and bipolar
      disorder. METHODS: PON1 status that is plasma PON1 abundance and three functional
      PON1 Q192R genotypes were assayed in 91 major depressed and 45 bipolar patients
      and compared to 199 normal controls. RESULTS: Major depression, but not bipolar
      disorder, was accompanied by lowered PON1 activity. PON1 activity was decreased
      by smoking and a diagnosis by genotype interaction (i.e. lower PON1 in major
      depression with the QQ genotype). Logistic regression showed that smoking by QQ
      genotype significantly increased the odds of bipolar disorder and that major
      depression was predicted by plasma PON1 activity, serum HDL cholesterol and
      interactions between genotype*smoking. DISCUSSION: The results suggest that
      lowered plasma PON1 activity is a trait marker of major depression and that
      PONQ192R gene-environment (smoking) interactions differentially predict the odds
      of depression and bipolar disorder. LIMITATIONS: Association studies are prone to
      a risk of false positive findings and replication is essential. CONCLUSIONS: The
      findings suggest that there are differential PON1 Q192R functional
      genotype*environment interactions in major depression and bipolar disorder. The
      effects of lowered PON1 activity may contribute to increased O&NS and immune
      inflammatory burden in depression. PON1 status may contribute to the comorbidity
      between depression and other immune- and O&NS-related disorders, e.g.
      cardiovascular disorder.

PMID- 24679386
TI  - Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual
      cingulate cortex for treatment-resistant depression: a systematic review and
      exploratory meta-analysis.
AB  - BACKGROUND: Deep brain stimulation (DBS) applied to the subgenual cingulate
      cortex (SCC) has been recently investigated as a potential treatment for severe
      and chronic treatment-resistant depression (TRD). Given its invasive and
      experimental nature, a comprehensive evaluation of its effectiveness and
      acceptability is of paramount importance. Therefore, we conducted the present
      systematic review and exploratory meta-analysis. METHODS: We searched the
      literature for English language prospective clinical trials on DBS of the SCC for
      TRD from 1999 through December 2012 using MEDLINE, EMBASE, PsycINFO, CENTRAL and
      SCOPUS, and performed a random effects exploratory meta-analysis using Event
      Rates and Hedges' g effect sizes. RESULTS: Data from 4 observational studies were
      included, totaling 66 subjects with severe and chronic TRD. Twelve-month response
      and remission rates following DBS treatment were 39.9% (95% CI=28.4% to 52.8%)
      and 26.3% (95% CI=13% to 45.9%), respectively. Also, depression scores at 12
      months post-DBS were significantly reduced (i.e., pooled Hedges' g effect size=
      1.89 [95% CI=-2.64 to -1.15, p<0.0001]). Also, there was a significant decrease
      in depression scores between 3 and 6 months (Hedges' g=-0.27, p=0.003), but no
      significant changes from months 6 to 12. Finally, dropout rates at 12 months were
      10.8% (95% CI=4.3% to 24.4%). LIMITATIONS: Small number of included studies (most
      of which were open label), and limited long-term effectiveness data. CONCLUSIONS:
      DBS applied to the SCC seems to be associated with relatively large response and
      remission rates in the short- and medium- to long-term in patients with severe
      TRD. Also, its maximal antidepressant effects are mostly observed within the
      first 6 months after device implantation. Nevertheless, these findings are
      clearly preliminary and future controlled trials should include larger and more
      representative samples, and focus on the identification of optimal
      neuroanatomical sites and stimulation parameters.

PMID- 24679387
TI  - Prothrombotic platelet phenotype in major depression: downregulation by
      antidepressant treatment.
AB  - BACKGROUND: Serotonergic mechanisms have been suggested as a link between major
      depression and cardiovascular risk. We investigated the existence of a
      prothrombotic condition in depressed patients and its possible modulation during
      treatment with a selective serotonin-reuptake inhibitor (SSRI). METHODS:
      Modifications in a series of biomarkers of platelet and coagulation activation
      were evaluated in blood from 19 patients with a major depression disorder (MDD)
      at the time of diagnosis, and at 8 and 24 weeks of treatment with escitalopram.
      Response of blood aliquots recirculated through a thrombogenic surface was
      assessed in a thrombosis model. Results were compared with those of 20 healthy
      matched controls. RESULTS: In comparison with controls, platelets from MDD
      patients showed elevated volumes (p<0.01), significantly enhanced aggregating
      response to arachidonic acid and augmented expression of GPIb, fibrinogen, factor
      V, and anionic phospholipids by flow cytometry (p<0.05). Clot firmness and
      procoagulant activity of platelet-associated tissue factor were also
      significantly elevated (p<0.05). Studies with circulating blood revealed
      increased fibrin formation in early diagnosed patients (71.1+/-9.5% vs. 45.8+/
      5.3%; p<0.05 vs. controls). After 24 weeks of treatment with escitalopram, the
      majority of the alterations observed were normalized, except for a residual
      increased expression of GPIIbIIIa (p<0.05) and persistent alterations in
      thromboelatometic parameters. LIMITATIONS: Despite the reduced number of followed
      up patients our findings were consistent reaching statistical significance.
      CONCLUSIONS: Our results reveal a prothrombotic phenotype in MDD patients. While
      continuous treatment with an SSRI downregulated the majority of the biomarkers
      analyzed, alterations in viscoelastic parameters of clot formation remained
      unaffected by the antidepressant treatment.

PMID- 24679388
TI  - Adolescent self-harm: a school-based study in Northern Ireland.
AB  - BACKGROUND: The prevalence of adolescent self-harm in Northern Ireland (NI) and
      its associated factors are unknown. Given the established relationship between
      conflict and mental health, and NI's recent history of conflict, it is important
      to investigate the factors associated with self-harm in NI. This study aimed to
      determine the prevalence of self-harm in NI adolescents and the factors
      associated with it, including exposure to the NI conflict. METHODS: Observational
      study of 3596 school pupils employing an anonymous self-report survey.
      Information was obtained on demographic characteristics, lifestyle, life events
      and problems, exposure to the NI conflict, social and internet influences, and
      psychological variables. RESULTS: Self-harm was reported by 10% of respondents.
      In univariate analyses, exposure to the NI conflict was associated with self-harm
      alongside established risk factors. In multivariate analyses, bullying and
      exposure to self-harm were associated with lifetime self-harm in both girls and
      boys. Alcohol use, drug use, physical and sexual abuse, and self-esteem were also
      associated with self-harm in girls. In boys, absence of exercise, sexual
      orientation concerns, anxiety and impulsivity were additional risk factors. The
      internet/social media and the self-harm of others were also key influences.
      LIMITATIONS: This is a cross-sectional study. CONCLUSIONS: The rate of self-harm
      was lower than elsewhere in the UK/Ireland. The study highlights the factors
      which should be considered in terms of risk assessment. In addition to
      established risk factors, the findings suggest that more research on the legacy
      of the NI conflict as well as the influence of new technologies warrant urgent
      attention.

PMID- 24679389
TI  - A comparison of bipolar disorders in children in Italy and the United States.
AB  - BACKGROUND: The clinical presentation of bipolar disorders, though clearly
      recognized in adolescents, remains controversial in younger children and across
      cultures. The aim of this study was to compare the clinical presentation of
      bipolar disorders in Italian and American children between ages 5 and 12 years.
      METHODS: Sixty-seven children from six outpatient programs were enrolled (Italian
      sample: n=40; American sample: n=28) between January 2010 and June 2011. Children
      and their parents were interviewed by experienced clinicians using the Washington
      University in St. Louis Schedule for Affective Disorders and Schizophrenia for
      School-Age Children-Present, Lifetime Version (WASH-U K-SADS). RESULTS: Italian
      children scored significantly higher on ratings of "elevated mood" (p=0.002),
      whereas American children scored significantly higher on ratings of "flight of
      ideas" (p=0.001) and "productivity" (p=0.001). Rates of comorbidity were
      different between groups. LIMITATIONS: Data were acquired from several sites in
      Italy as compared to from a single American site. Medication and educational
      information were not systematically collected. Furthermore, the sample collected
      may only reflect characteristics of a less severely ill group of bipolar
      children. CONCLUSIONS: Our comparison of Italian and American children with early
      onset bipolar disorders found that the phenotype of bipolar spectrum disorders is
      largely shared across cultures, although psychiatric comorbidities differed.

PMID- 24679390
TI  - Do the dissociative side effects of ketamine mediate its antidepressant effects?
AB  - BACKGROUND: The N-methyl-d-aspartate receptor antagonist ketamine has rapid
      antidepressant effects in major depression. Psychotomimetic symptoms,
      dissociation and hemodynamic changes are known side effects of ketamine, but it
      is unclear if these side effects relate to its antidepressant efficacy. METHODS:
      Data from 108 treatment-resistant inpatients meeting criteria for major
      depressive disorder and bipolar disorder who received a single subanesthetic
      ketamine infusion were analyzed. Pearson correlations were performed to examine
      potential associations between rapid changes in dissociation and psychotomimesis
      with the Clinician-Administered Dissociative States Scale (CADSS) and Brief
      Psychiatric Rating Scale (BPRS), respectively, manic symptoms with Young Mania
      Rating Scale (YMRS), and vital sign changes, with percent change in the 17-item
      Hamilton Depression Rating scale (HDRS) at 40 and 230min and Days 1 and 7.
      RESULTS: Pearson correlations showed significant association between increased
      CADSS score at 40min and percent improvement with ketamine in HDRS at 230min (r=
      0.35, p=0.007) and Day 7 (r=-0.41, p=0.01). Changes in YMRS or BPRS Positive
      Symptom score at 40min were not significantly correlated with percent HDRS
      improvement at any time point with ketamine. Changes in systolic blood pressure,
      diastolic blood pressure, and pulse were also not significantly related to HDRS
      change. LIMITATIONS: Secondary data analysis, combined diagnostic groups,
      potential unblinding. CONCLUSIONS: Among the examined mediators of ketamine's
      antidepressant response, only dissociative side effects predicted a more robust
      and sustained antidepressant. Prospective, mechanistic investigations are
      critically needed to understand why intra-infusion dissociation correlates with a
      more robust antidepressant efficacy of ketamine.

PMID- 24679391
TI  - The association between serum lipid levels, suicide ideation, and central
      serotonergic activity in patients with major depressive disorder.
AB  - BACKGROUND: There is some evidence that low lipid levels cause suicide in
      depressed patients. The purpose of this study was to identify whether low serum
      lipid levels are associated with suicide ideation or are correlated with central
      serotonin function. METHODS: Auditory processing for the loudness dependence of
      auditory evoked potentials (LDAEP) was measured in 73 outpatients with major
      depressive disorder. The Hamilton Depression Rating Scale (HAMD) and the Beck
      Depression Inventory (BDI) were administered on the same day as measurement of
      the LDAEP. In addition, serum levels of total cholesterol, low-density
      lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels
      were measured. All subjects had received antidepressant monotherapy. RESULTS: The
      depressed subjects were divided into those with and without suicide ideation
      according to the score for HAMD item 3 or BDI item 9. TG levels differed
      significantly between the two groups, whereas body mass index (BMI), total
      cholesterol, LDL, HDL, and LDAEP did not. The scores for HAMD item 3 and BDI item
      9 were negatively correlated with TG levels (p=0.045 and 0.026, respectively).
      The LDAEP was negatively correlated with TG levels (p=0.012). Although there was
      tendency toward a negative correlation between the LDAEP and serum LDL, it did
      not reach statistical significance (p=0.068). LIMITATIONS: The cross-sectional
      design of this study means that baseline serum lipid levels were not measured.
      CONCLUSION: The findings of this study revealed a relationship between TG and
      suicide ideation that is independent of both BMI and body weight. Furthermore,
      serum lipid levels were associated with central serotonergic activity, as
      assessed using the LDAEP.

PMID- 24679392
TI  - Children at risk for depression: memory biases, self-schemas, and genotypic
      variation.
AB  - BACKGROUND: Daughters of depressed mothers are at increased risk for developing a
      depressive disorder. We know relatively little, however, about the specific
      factors that contribute to this elevated risk. The present study investigated the
      effects of familial risk for depression and the 5-HTTLPR and COMT Val158Met
      polymorphisms, which have been associated with risk for depression, on biases in
      endorsement of and memory for positive and negative adjectives. METHODS:
      Following a negative mood induction, 60 girls between the ages of 10 and 14 who
      had recurrent depressed mothers (high risk for depression) and 91 age-matched
      daughters of never-disordered mothers (low risk for depression) completed a Self
      Referent Encoding Task in which they decided whether negative and positive
      adjectives described them. Following the task they were asked to recall as many
      of the adjectives as they could. RESULTS: Despite the absence of significant
      group differences in endorsement of positive or negative adjectives, high-risk
      girls with the COMT Val158Met Val/Val polymorphism recalled more positive (but
      not negative) words that they had endorsed than did high-risk girls who were
      homozygous for the Met allele. COMT was not associated with recall of valenced
      adjectives in low-risk girls. Across risk groups, 5-HTTLPR polymorphism was not
      associated with recall of valenced adjectives. LIMITATIONS: Even with over 150
      participants, there were relatively small numbers in some of the cells of this
      study, limiting its statistical power. CONCLUSIONS: These results suggest that
      assessing the interaction of familial risk status and COMT polymorphism is
      important in understanding the development of depressive disorders.

PMID- 24679393
TI  - The impact of lifestyle factors on the 2-year course of depressive and/or anxiety
      disorders.
AB  - BACKGROUND: Although depressed and anxious patients often show an unhealthy
      lifestyle, much is still unclear about its impact on the natural course of
      disorders. This study will examine whether physical activity, smoking and alcohol
      consumption predicted the 2-year course of depressive and/or anxiety disorders.
      METHODS: In a large sample of depressed and/or anxious patients (n=1275), we
      examined whether baseline physical activity, smoking and alcohol consumption
      independently predicted the course of disorders at 2-year follow-up. The
      persistence of DSM-IV depressive and/or anxiety disorders (primary outcome) and
      the severity of depressive and anxiety symptoms (secondary outcomes) were
      considered. Confounding effects of baseline severity of psychopathology,
      sociodemographics, somatic health indicators and treatment factors were taken
      into account. RESULTS: The persistence of disorders was significantly increased
      in patients with low physical activity (61.2%), but not moderate physical
      activity (54.4%), compared to patients with high physical activity (49.2%). This
      association remained significant after adjustment for baseline severity of
      psychopathology, other lifestyle factors (smoking and alcohol consumption),
      sociodemographics, somatic health indicators and treatment factors. Similar
      results were found for the course of depressive and anxiety symptoms. Neither
      smoking nor alcohol consumption was related to the course of depressive and/or
      anxiety disorders. LIMITATIONS: Assessments of lifestyle factors were based on
      self-report and may be subject to recall and social desirability bias.
      CONCLUSIONS: Low physical activity, but not heavy smoking or alcohol consumption,
      was a strong and independent risk factor of an unfavorable course of depressive
      and/or anxiety disorders and may be an important therapeutic target in treatment.

PMID- 24679394
TI  - Polymorphism of circadian clock genes and temperamental dimensions of the TEMPS-A
      in bipolar disorder.
AB  - BACKGROUND: Previously, we found correlations between lithium efficacy in bipolar
      disorder and temperamental dimensions of the TEMPS-A and also genes involved in
      the regulation of biological rhythms ("clock" genes). Here, were attempted to
      investigate an association between multiple, single nucleotide polymorphisms
      (SNPs) of four clock genes (CLOCK, ARNTL, TIM, PER3) and temperamental dimensions
      of the TEMPS-A, in bipolar patients. METHODS: The study included 70 patients with
      bipolar disorder (20 males, 50 females), with a mean age of 59+/-12 years. The
      TEMPS-A questionnaire, 110 questions version, was used assessing five temperament
      domains: depressive, cyclothymic, hyperthymic, irritable and anxious. Genotyping
      was done for 9 SNPs of the CLOCK gene, 18 SNPs of the ARNTL gene, 6 SNPs of the
      TIM gene and 5 SNPs of the PER3 gene. RESULTS: An association with hyperthymic
      temperament was found for three, and with anxious temperament for four SNPs of
      the ARTL gene. An association of cyclothymic temperament was found with two SNPs
      of the TIM gene and of depressive temperament with one SNP of the PER3 gene. No
      association was observed with SNPs of the CLOCK gene. LIMITATIONS: Relatively
      small number of patients studied and insufficient correction for multiple
      testing. CONCLUSIONS: These results may suggest that the ARNTL, TIM and PER3
      genes may be associated with temperamental dimensions measured by the TEMPS-A,
      each of this gene being specific to given temperamental dimension. Of special
      interest may be the polymorphisms of ARNTL gene also connected with
      predisposition to bipolar mood disorder and/or lithium response.

PMID- 24679395
TI  - Cost-effectiveness analysis of a collaborative care programme for depression in
      primary care.
AB  - BACKGROUND: Collaborative care programmes lead to better outcomes in the
      management of depression. A programme of this nature has demonstrated its
      effectiveness in primary care in Spain. Our objective was to evaluate the cost
      effectiveness of this programme compared to usual care. METHODS: A bottom-up cost
      effectiveness analysis was conducted within a randomized controlled trial (2007
      2010). The intervention consisted of a collaborative care programme with
      clinical, educational and organizational procedures. Outcomes were monitored over
      a 12 months period. Primary outcomes were incremental cost-effectiveness ratios
      (ICER): mean differences in costs divided by quality-adjusted life years (QALY)
      and mean differences in costs divided by depression-free days (DFD). Analyses
      were performed from a healthcare system perspective (considering healthcare
      costs) and from a society perspective (including healthcare costs plus loss of
      productivity costs). RESULTS: Three hundred and thirty-eight adult patients with
      major depression were assessed at baseline. Only patients with complete data were
      included in the primary analysis (166 in the intervention group and 126 in the
      control group). From a healthcare perspective, the average incremental cost of
      the programme compared to usual care was ?182.53 (p<0.001). Incremental
      effectiveness was 0.045 QALY (p=0.017) and 40.09 DFD (p=0.011). ICERs were
      ?4,056/QALY and ?4.55/DFD. These estimates and their uncertainty are graphically
      represented in the cost-effectiveness plane. LIMITATIONS: The amount of 13.6% of
      patients with incomplete data may have introduced a bias. Available data about
      non-healthcare costs were limited, although they may represent most of the total
      cost of depression. CONCLUSIONS: The intervention yields better outcomes than
      usual care with a modest increase in costs, resulting in favourable ICERs. This
      supports the recommendation for its implementation.

PMID- 24679396
TI  - Residual symptoms and functional performance in a large sample of euthymic
      bipolar patients in France (the OPTHYMUM study).
AB  - BACKGROUND: Some residual symptoms were found to be associated with impaired
      functioning in euthymic bipolar patients, but their impact and relevance are
      unclear in clinical practice. We re-examined the functional influence of a large
      set of residual symptoms in 525 euthymic bipolar outpatients using self- and
      clinician-rated questionnaires (OPTHYMUM study). METHODS: This was a multi
      centre, cross-sectional, non-interventional study of adult bipolar outpatients.
      All patients were euthymic at the time of assessment (YMRS score <8 and BDRS
      <=8). Patients with low functioning (GAF score <60) were compared with the rest
      of the sample. Patients filled in specific questionnaires concerning their
      perceptions of different residual and subsyndromal symptoms. RESULTS: Ninety
      seven (97) psychiatrists included 525 patients. Of them, 35 patients had a GAF
      score <60. These "low functioning patients" were more frequently unemployed, had
      presented more manic episodes and psychotic symptoms, used more atypical
      antipsychotics or benzodiazepines and received less adjunctive psychotherapy.
      Concerning residual symptoms, they had more frequent emotional subsyndromal
      symptoms, disruption of circadian rhythms and sexual disorders. They perceived
      some cognitive deficits and suffered more social and family stigma. LIMITATIONS:
      Our study used an arbitrary GAF cut-off score (60) to separate bipolar patients
      in two groups (low and satisfactory functioning). CONCLUSIONS: Residual symptoms
      are associated with functional impairment and may represent specific treatment
      targets. A personalized approach through specific psychotherapeutic programs may
      lead to more efficient support by the clinician.

PMID- 24679397
TI  - Maternal anxiety during pregnancy and adverse birth outcomes: a systematic review
      and meta-analysis of prospective cohort studies.
AB  - BACKGROUND: Previous studies concerning the association between maternal anxiety
      during pregnancy and adverse birth outcomes have provided controversial findings.
      METHODS: In this systematic review, a meta-analysis was utilized to investigate
      the association between maternal anxiety and preterm birth (PTB) and/or low birth
      weight (LBW). Literature was searched until June 2013. Only prospective cohort
      studies that reported data on maternal anxiety during pregnancy with PTB and/or
      LBW were included. Pooled relative risks (RRs) with 95% confidence intervals
      (CIs) were calculated using fixed or random effects models depending on the size
      of heterogeneity. RESULTS: Twelve studies totaling 17,304 pregnant women reported
      PTB data; and six studies totaling 4948 pregnant women reported LBW data.
      Maternal anxiety during pregnancy was associated with significant increased risk
      of PTB (pooled RR=1.50, 95% CI=1.33-1.70) and LBW (pooled RR=1.76, 95% CI=1.32
      2.33). LIMITATIONS: Potential moderators could not be adequately considered due
      to insufficient information. In addition, the effects of different types of
      anxiety disorder on the risk of these adverse birth outcomes could not be
      investigated. CONCLUSIONS: The results suggested that maternal anxiety during
      pregnancy was positively related to an increased risk of PTB and LBW. Healthcare
      providers should give close attention to anxiety in pregnant women and provide
      appropriate mental health support in order to improve outcomes for both mothers
      and infants.

PMID- 24679398
TI  - Assessment of prevalence and determinants of posttraumatic stress disorder and
      depression symptoms in adults survivors of earthquake in Haiti after 30 months.
AB  - BACKGROUND: On January 12, 2010, a powerful 7.0 magnitude earthquake struck the
      Republic of Haiti and destroyed Port-au-Prince, the capital and others cities
      across the country. While some studies have examined the long-term traumatic
      effects of the seismic event on children and adolescents victims, so far no study
      has examined the consequences on adults generally. As such, this study aims to
      investigate the traumatic consequences of the earthquake among adults related to
      degree of exposure, peritraumatic distress, depressive symptoms and
      sociodemographic factors two and a half years after. In addition, predictive
      factors of PTSD and depressive symptoms were also identified. METHODS: From June
      to July 2012, a total of 1355 adults (660 women) was assessed by means the
      traumatic exposure questionnaire, the Life Events Checklist subscale, the
      Peritraumatic Distress Inventory (PDI), the Impact of Event Scale - Revised (IES
      R) and the Beck Depression Inventory (BDI), in addition to social demographic
      characteristics. RESULTS: The prevalence rates of PTSD and depressive symptoms
      were 36.75% (498 cases) and 25.98% (352 cases) respectively. The risk factors for
      PTSD and depressive symptoms were young and old age, female gender, unemployed
      status and low level of education. The bests predictives variables were
      peritraumatic distress for PTSD (beta=.57, p<.0001) and for depressive symptoms
      (beta=.21, p<.0001). The commorbidity between PTSD and depression was 13.36%.
      CONCLUSIONS: This study found that psychological symptoms are frequent event 30
      months after the earthquake. The different mental health care providers, the
      public health ministry, NGOs working on the ground in Haiti should design
      programmes in order to aid the psychological wellbeing of the population
      focussing on youth, older and retired adults, females, people with low levels of
      education and those who do not work.

PMID- 24679399
TI  - The effects of psychotherapies for major depression in adults on remission,
      recovery and improvement: a meta-analysis.
AB  - BACKGROUND: Standardised effect sizes have been criticized because they are
      difficult to interpret and offer little clinical information. This meta-analyses
      examine the extent of actual improvement, the absolute numbers of patients no
      longer meeting criteria for major depression, and absolute rates of response and
      remission. METHODS: We conducted a meta-analysis of 92 studies with 181
      conditions (134 psychotherapy and 47 control conditions) with 6937 patients
      meeting criteria for major depressive disorder. Within these conditions, we
      calculated the absolute number of patients no longer meeting criteria for major
      depression, rates of response and remission, and the absolute reduction on the
      BDI, BDI-II, and HAM-D. RESULTS: After treatment, 62% of patients no longer met
      criteria for MDD in the psychotherapy conditions. However, 43% of participants in
      the control conditions and 48% of people in the care-as-usual conditions no
      longer met criteria for MDD, suggesting that the additional value of
      psychotherapy compared to care-as-usual would be 14%. For response and remission,
      comparable results were found, with less than half of the patients meeting
      criteria for response and remission after psychotherapy. Additionally, a
      considerable proportion of response and remission was also found in control
      conditions. In the psychotherapy conditions, scores on the BDI were reduced by
      13.42 points, 15.12 points on the BDI-II, and 10.28 points on the HAM-D. In the
      control conditions, these reductions were 4.56, 4.68, and 5.29. DISCUSSION:
      Psychotherapy contributes to improvement in depressed patients, but improvement
      in control conditions is also considerable.

PMID- 24679400
TI  - Effects of antidepressant medication on emotion regulation in depressed patients:
      an iSPOT-D report.
AB  - BACKGROUND: Antidepressant medication (ADM) is thought to reduce depressive
      symptoms by altering emotion-generative brain systems. However, it is unknown
      whether successful ADM treatment is associated with changes in psychobehavioral
      strategies used to regulate emotions. We examined depressive symptoms and emotion
      regulation strategies before and after ADM in the international Study to Predict
      Optimized Treatment in Depression (iSPOT-D). METHODS: The study enrolled 1008
      adult patients with MDD (18-65 years old) from 18 primary and psychiatric care
      sites worldwide. Patients were randomly assigned to an 8-week course of
      escitalopram, sertraline, or venlafaxine-extended-release. We examined whether
      ADM is associated with changes in suppression, usually associated with
      maladaptive outcomes, and reappraisal, usually associated with adaptive outcomes.
      We also tested whether changes in emotion regulation predict changes in
      depressive symptoms following ADM. RESULTS: We observed more adaptive emotion
      regulation (decreased use of suppression and increased use of reappraisal)
      following ADM. Furthermore, the largest improvements in emotion regulation were
      associated with the best treatment outcomes. LIMITATIONS: Because we assessed
      acute outcomes, it is not yet known if the effects of ADM on emotion regulation
      would persist over time. CONCLUSIONS: ADMs are associated with acute, adaptive
      changes in the psychobehavioral strategies used to regulate emotions.

PMID- 24679401
TI  - Nonverbal dominance behavior among individuals at risk for mania.
AB  - BACKGROUND: Research suggests that people with bipolar disorder may be highly
      motivated to attain dominance and may over-estimate their social power (Johnson
      and Carver, 2012). This manic temperament may provide an adaptive advantage in
      the pursuit of dominance and leadership (Akiskal and Akiskal, 1992). It was
      hypothesized that people at high risk for bipolar disorder, as defined by the
      Hypomanic Personality Scale (HPS), would fail to assume a submissive role when it
      was appropriate to do so. METHOD: Participants (81 undergraduates) completed an
      image description task with a confederate. Participants were randomly assigned to
      interact with a confederate who assumed one of three nonverbal postures: dominant
      (expanded), neutral, or submissive (constricted). Nonverbal dominance behavior
      was defined as the rate at which participants expanded their body span during the
      task. RESULTS: Consistent with hypotheses, an ANOVA indicated an interaction of
      Mania risk x Dominance condition on body expansion. Whereas participants with low
      mania risk (HPS scores) adapted complementary behavior in response to the
      confederate, participants with high mania risk demonstrated a consistently
      dominant (expanded) nonverbal posture. LIMITATIONS: A major limitation of this
      study is the use of an analog measure of mania risk in place of clinical
      diagnoses. CONCLUSIONS: In this experiment, participants at high risk for mania
      maintained a dominant posture even when submissiveness would have been more
      appropriate. It is argued that persistent dominance behavior may play an
      important role in the interpersonal interactions of individuals at risk for
      bipolar disorder.

PMID- 24679402
TI  - Feeling connected again: interventions that increase social identification reduce
      depression symptoms in community and clinical settings.
AB  - BACKGROUND: Clinical depression is often preceded by social withdrawal, however,
      limited research has examined whether depressive symptoms are alleviated by
      interventions that increase social contact. In particular, no research has
      investigated whether social identification (the sense of being part of a group)
      moderates the impact of social interventions. METHOD: We test this in two
      longitudinal intervention studies. In Study 1 (N=52), participants at risk of
      depression joined a community recreation group; in Study 2 (N=92) adults with
      diagnosed depression joined a clinical psychotherapy group. RESULTS: In both the
      studies, social identification predicted recovery from depression after
      controlling for initial depression severity, frequency of attendance, and group
      type. In Study 2, benefits of social identification were larger for depression
      symptoms than for anxiety symptoms or quality of life. LIMITATION: Social
      identification is subjective and psychological, and therefore participants could
      not be randomly assigned to high and low social identification conditions.
      CONCLUSIONS: Findings have implications for health practitioners in clinical and
      community settings, suggesting that facilitating social participation is
      effective and cost-effective in treating depression.

PMID- 24679403
TI  - Under-reporting bipolar disorder in large-scale epidemiologic studies.
AB  - BACKGROUND: To investigate if the prevalence of bipolar disorder in epidemiologic
      studies is an underestimate, as suggested by clinical studies. METHODS: We
      analyzed data from 8 countries that participated in the World Mental Health
      Survey Initiative (n=47,552). We identified 6.8% and 18.9% of the sample who we
      think were screened out inappropriately (SCI) from the euphoric and irritable
      bipolar sections respectively. We compared them to those who were allowed to
      continue the section (CONT, 2.6% of the sample for euphoric; 1.0% for irritable)
      and to the reference group (REF, 69.5% of the sample). RESULTS: The SCI group had
      consistently higher rates of major depression (29.1% vs. 6.4%), earlier age of
      onset (24.3y vs. 32.4y), more suicide attempts (13.3% vs. 5.9%), and more
      episodes (4.2 vs. 2.7) than the REF for the euphoric group. Similar findings
      exist for the irritable group. Also, comorbidity with anxiety, disruptive
      behavior disorders and substance use were much higher than the REF. LIMITATIONS:
      As with all epidemiologic studies, recall bias cannot be ruled out. CONCLUSIONS:
      The findings above suggest that a number of the SCI subjects belong to the
      bipolar group. A revision of instruments used in epidemiologic research will
      probably prove what clinical studies have been showing that bipolar disorder is
      more common than has been reported.

PMID- 24679404
TI  - Reproductive tract inflammatory disease in postpartum dairy cows.
AB  - Up to half of dairy cows are affected by at least one of metritis, purulent
      vaginal discharge, endometritis or cervicitis in the postpartum period. These
      conditions result from inadequate immune response to bacterial infection (failure
      to clear pathogenic bacteria from the uterus) or persistent inflammation that
      impairs rather than enhances reproductive function. The degree of mobilization of
      fat and how effectively it is used as a metabolic fuel is well recognized as a
      risk factor for metabolic and infectious disease. Release of non-esterified fatty
      acids has direct effects on liver and immune function but also produces pro
      inflammatory cytokines (tumor necrosis factor alpha and interleukin-6), which
      contribute to systemic inflammation and to insulin resistance. Therefore,
      reproductive tract inflammatory disease may be a function of both local and
      systemic inflammatory stimuli and regulation as well as regulation of fat
      metabolism. Better understanding of variables associated with insulin resistance
      and inflammatory regulation in the liver and adipose tissue may lead to
      improvement of reproductive tract health. This paper reviews factors that may
      contribute to postpartum reproductive tract inflammatory diseases in dairy cows
      and their inter-relationships, impacts and treatment. 

PMID- 24679406
TI  - Ultra-fast light-curing resin composite with increased conversion and reduced
      monomer elution.
AB  - OBJECTIVES: To test the null hypotheses that photoactive resin composites
      containing a Type I photoinitiator would exhibit reduced DC or increased monomer
      elution at substantially short curing times compared with materials based on a
      Type 2 ketone/amine system. METHODS: Two experimental resin composites were
      prepared, using either Lucirin-TPO or camphorquinone/DMAEMA. Specimens were light
      cured using appropriate spectral emission that coincided with the absorption
      properties of each initiator using different irradiation protocols (0.5, 1, 3, 9s
      at 500, 1000 and 2000mW/cm(2) for Lucirin-TPO based composites and 20 or 40s at
      1000mW/cm(2) for Lucirin-TPO and camphorquinone-based composites). Degree of
      conversion (DC) was measured by Raman spectroscopy, propagating radical
      concentrations were collected by means of electron paramagnetic resonance (EPR)
      and monomer leaching was characterized using high-performance liquid
      chromatography (HPLC). RESULTS: The null hypotheses were rejected, except for a
      single irradiation protocol (0.5s @ 500mW/cm(2)). Lucirin-TPO-based composites
      could cure 20 times faster and release at least 4 times less monomers in
      comparison to camphorquinone-based composites. At 1000mW/cm(2), and 1s
      irradiation time for curing times of 1s, Lucirin-TPO based composites displayed
      10% higher DC. The difference in polymerization efficiency of Lucirin-TPO
      compared with camphorquinone-based resin composites were explained using EPR; the
      former showing a significantly greater yield of radicals which varied
      logarithmically with radiant exposure. SIGNIFICANCE: Lucirin-TPO is substantially
      more efficient at absorbing and converting photon energy when using a curing
      light with an appropriate spectral emission and otherwise a limitation noted in
      several previous publications. At concentrations of 0.0134mol/L, Lucirin-TPO
      based composites require a minimum light intensity of 1000mW/cm(2) and an
      exposure time of 1s to provide significantly improved DC and minimal elution
      compared with a conventional photoinitiator system. The use of a wide range of
      curing protocols in the current experiment has realized the significant potential
      of Lucirin-TPO and its impact for clinical applications, in replacement to
      materials using camphorquinone.

PMID- 24679405
TI  - Epithelial sodium channel modulates platelet collagen activation.
AB  - Activated platelets adhere to the exposed subendothelial extracellular matrix and
      undergo a rapid cytoskeletal rearrangement resulting in shape change and release
      of their intracellular dense and alpha granule contents to avoid hemorrhage. A
      central step in this process is the elevation of the intracellular Ca(2+)
      concentration through its release from intracellular stores and on throughout its
      influx from the extracellular space. The Epithelial sodium channel (ENaC) is a
      highly selective Na(+) channel involved in mechanosensation, nociception, fluid
      volume homeostasis, and control of arterial blood pressure. The present study
      describes the expression, distribution, and participation of ENaC in platelet
      migration and granule secretion using pharmacological inhibition with amiloride.
      Our biochemical and confocal analysis in suspended and adhered platelets suggests
      that ENaC is associated with Intermediate filaments (IF) and with Dystrophin
      associated proteins (DAP) via alpha-syntrophin and beta-dystroglycan. Migration
      assays, quantification of soluble P-selectin, and serotonin release suggest that
      ENaC is dispensable for migration and alpha and dense granule secretion, whereas
      Na(+) influx through this channel is fundamental for platelet collagen
      activation. 

PMID- 24679407
TI  - Chemiluminescence detection of protein in capillary electrophoresis using aptamer
      functionalized gold nanoparticles as biosensing platform.
AB  - Highly sensitive and selective detection of disease-related proteins play
      critical roles in clinical practice and diagnostic assays. Herein, we proposed a
      highly selective and ultrasensitive chemiluminescence (CL) method for protein
      detection in capillary electrophoresis (CE) using aptamer-functionalized gold
      nanoparticles (AuNPs) as biosensing platform. In this protocol, AuNPs were
      synthesized and conjugated with aptamer to form AuNPs-aptamer. Using thrombin and
      thrombin binding aptamer as an initial proof-of-concept recognization pair, AuNPs
      aptamer was linked to thrombin to produce an AuNPs-aptamer-thrombin complex. The
      resulted complex and unbound AuNPs-aptamer were separated in CE and detected with
      luminol-H2O2 CL system. The developed strategy produced an ultrasensitive
      detection of thrombin down to 13.5 fmol/L (S/N=3) with a linear range from 0.033
      to 66.0 pmol/L. The application of the present protocol was demonstrated by
      analyzing thrombin in human plasma samples with the recoveries of 87.6-116.8%.
      This novel strategy has many outstanding merits including high specificity of
      aptamer, excellent catalysis behavior of AuNPs, high sensitivity of CL detection,
      and high separation efficiency of CE.

PMID- 24679408
TI  - Development of on-line comprehensive two-dimensional liquid chromatography method
      for the separation of biomass compounds.
AB  - Comprehensive on-line two-dimensional liquid chromatography (on-line LC * LC) was
      used for the characterization of bio-oils obtained by fast pyrolysis of
      lignocellulosic biomass. The resulting bio-oil contains a large number of
      oxygenated chemical families and must therefore be upgraded before being used as
      drop-in transportation biofuels. The good knowledge of its complex composition is
      essential for optimizing the mandatory bio-oil upgrading process to biofuels,
      thereby requiring powerful separation techniques designed to be hyphenated to
      mass spectrometry detection (LC * LC-MS). In this study, reversed phase
      conditions were optimized in both dimensions for the RPLC * RPLC separation of
      the aqueous fraction of bio-oils. The first step of method development consisted
      in searching for a suitable set of RP-conditions via the screening of a large
      number of RP-systems (made up of different stationary phases and/or mobile phases
      and/or temperature). The practical peak capacity and the degree of orthogonality
      were calculated for a sample of 38 representative compounds, both descriptors
      having been considered as selection criterion. Two different couplings were
      chosen and evaluated for the RPLC * RPLC separation of the 38 representative
      compounds. The best of both, in terms of real practical peak capacity, was
      further successfully applied to the separation of the aqueous phase of a
      partially dehydroxygenated bio-oil.

PMID- 24679409
TI  - Direct separation of the enantiomers of oxaliplatin on a cellulose-based chiral
      stationary phase in hydrophilic interaction liquid chromatography mode.
AB  - (R,R)-oxaliplatin is an anticancer enantiopure active pharmaceutical ingredient.
      Little attention has been devoted to the analysis of its enantiomeric
      composition. The enantioselective HPLC method reported in the current
      Pharmacopoeias shows clear disadvantages with regard to the low resolution and
      long elution times. In this work, it has been proven the applicability of a last
      generation polysaccharide-based chiral stationary phase (CSP), i.e. the Chiralpak
      IC-3, in the enantioseparation of oxaliplatin. Experimental results demonstrated
      the benefits arising from the development of enantioselective hydrophilic
      interaction liquid chromatography (HILIC) based strategies. A baseline separation
      with resolution factor of 5.8 was achieved using a 100mm*4.6mm I.D. IC-3 column
      set at the temperature of 40 degrees C and a mobile phase consisting of
      acetonitrile-water 100:5 mixture. At a flow rate of 1mLmin(-1) the separation was
      completed within 8min. The optimized method was proven to be sensitive with LOD
      and LOQ of the enantiomeric impurity of 0.07 and 0.21MUgmL(-1), respectively. 

PMID- 24679410
TI  - In-port derivatization coupled to different extraction techniques for the
      determination of alkylphenols in environmental water samples.
AB  - Large volume injection (LVI)-in port silylation coupled to gas chromatography
      mass spectrometry (GC-MS) for the determination of alkylphenols (APs) in water
      samples applying four different extraction approaches was evaluated. Among the
      variables studied for in-port derivatization, vent time, cryo-focusing
      temperature and the ratio solvent volume/N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA) volume were optimized using an
      experimental design approach. Regarding the extraction techniques, different
      approaches previously optimized in the research group were tested. On the one
      hand different polymeric materials were tested: silicon rod (SR),
      polyethersulfone (PES) and polydimethylsiloxane (PDMS), the latter in the stir
      bar sorptive extraction format (SBSE-PDMS). PES was chosen among the polymeric
      materials due to the higher recoveries (compared with SR) and lower price
      (compared to PDMS in the stir-bar sorptive extraction, SBSE-PDMS). Both MASE and
      PES protocols were selected at this point for further method validation and
      application to real samples. Finally, the developed methods were validated and
      applied to the determination of target analytes in various aqueous environmental
      matrices, including estuarine water and wastewater. Acceptable repeatability in
      the case of MASE (5-17%) and PES (7-21%) procedures and method detection limits
      (MDLs, 5-123 and 28-328 ng L(-1) for PES and MASE, respectively) were obtained
      for most analytes. In terms of apparent recoveries in the presence of matrix,
      estuarine and effluent samples showed no significant matrix effect (apparent
      recoveries in the 73-121% for PES and 74-128% for MASE), while a stronger matrix
      effect was observed for influent wastewater samples (98-132% for PES and 65-156%
      for MASE). Both MASE and PES extractions combined with LVI-in-port derivatization
      GC-MS were applied to the determination of APs in the estuary of Bilbao (Gulf of
      Biscay, Spain).

PMID- 24679411
TI  - Eco-friendly microextraction method for the quantitative speciation of 13
      haloacetic acids in water.
AB  - This paper describes the first micro liquid-liquid extraction (MLLE) gas
      chromatography-mass spectrometry (GC-MS) method for the speciation of emerging
      iodinated acetic acids, along with conventional chlorinated and brominated acids
      in water. The haloacetic acids (HAAs) were derivatised using 3 reagents for their
      methylation, both in aqueous and organic media. The acidic methanol
      derivatisation in aqueous medium provided the best efficiency, requiring minimal
      sample manipulation. The derivatisation yield was improved through the use of
      microwave energy that drastically reduced reaction time (2 min). The HAA methyl
      esters were finally extracted using 250 MUL of methyl tert-butyl ether. This MLLE
      combined with the use of a large-volume sample injection coupled to a programmed
      temperature vaporiser-GC-MS improved the sensitivity of the method and minimised
      the generation of hazardous residues in accordance with the principles of "Green
      Chemistry". Detection and quantification limits (excepting tribromoacetic acid)
      within the range of 0.01-0.15 MUg/L and 0.03-0.5 MUg/L, respectively, were
      obtained and the relative standard deviation was lower than 10%. The eco-friendly
      method was applied to the speciation of the 13 HAAs in treated (chlorinated and
      chloraminated water) and untreated water. Up to 8 HAAs were found at detectable
      levels in treated water. The highly toxic monoiodoacetic acid was detected in
      almost all the chloraminated water.

PMID- 24679412
TI  - Comparison of cytotoxic and anti-platelet activities of polyphenolic extracts
      from Arnica montana flowers and Juglans regia husks.
AB  - Polyphenolic compounds of plant origin are well known to be beneficial to human
      health: they exert protective effects on haemostasis and have a particular
      influence on blood platelets. However, the anti-platelet properties of
      polyphenolic compounds observed so far have not been weighed against their
      potential cytotoxic action against platelets. The aim of this study was to
      demonstrate that anti-platelet and cytotoxic effects on blood platelets may
      interfere and therefore, may often lead to confusion when evaluating the
      properties of plant extracts or other agents towards blood platelets. The anti
      platelet and cytotoxic in vitro effects of plant extracts obtained from the husks
      of walnuts (J. regia) and flowers of arnica (A. montana) on platelet reactivity
      and viability were examined. Platelet function was assessed using standard
      methods (flow cytometry: P-selectin expression, activation of GPIIbIIIa complex,
      vasodilator-stimulated phosphoprotein, VASP index; turbidimetric and impedance
      aggregometry) and newly set assays (flow cytometric monitoring of platelet
      cytotoxicity). The results reveal that none of the studied plant extracts
      demonstrated cytotoxicity towards blood platelets. The phenolic acid-rich extract
      of A. montana (7.5 and 15 ug/ml) significantly reduced the ADP-induced
      aggregation in both whole blood and PRP, and decreased the platelet reactivity
      index (PRI; VASP phosphorylation) in whole blood, while showing excellent
      antioxidant capacity. The extract of J. regia husks significantly reduced ADP
      induced platelet aggregation in whole blood when applied at 7.5 ug/ml, and only
      slightly decreased the PRI at 15 ug/ml. Both examined extracts suppressed
      platelet hyper-reactivity, and such influence did not interfere with cytotoxic
      effects of the extracts. Thus, its high polyphenol content, excellent antioxidant
      capacity and distinct anti-platelet properties, in combination with its lack of
      toxicity, make the extract of A. montana flowers a possible candidate as an anti
      platelet agent or a compounding diet supplement.

PMID- 24679413
TI  - Adverse medical complications: an under-reported contributory cause of death in
      New York City.
AB  - OBJECTIVES: The current death certification system in the USA fails to accurately
      track deaths due to adverse medical events. The aim of this study was to
      demonstrate the under-reporting of deaths due to adverse medical events due to
      limitations in the current death certification/reporting system, and the benefits
      of using the term 'therapeutic complication' as the manner of death. STUDY
      DESIGN: Retrospective review and comparison of death certificates and vital
      statistical coding. METHODS: The manner of death is certified as a therapeutic
      complication when death is caused by predictable complications of appropriate
      therapy, and would not have occurred but for the medical intervention. Based on
      medical examiner records, complications that caused or contributed to deaths over
      a five-year period were examined retrospectively. These fatalities were compared
      with deaths coded as medical and surgical complications by the New York City
      Bureau of Vital Statistics. RESULTS: The Medical Examiner's Office certified 2471
      deaths as therapeutic complications and 312 deaths as accidents occurring in
      healthcare facilities. In contrast, the New York City Bureau of Vital Statistics
      reported 188 deaths due to complications of medical and surgical care.
      CONCLUSIONS: Use of the term 'therapeutic complication' as the manner of death
      identified nearly 14 times more deaths than were reported by the New York City
      Bureau of Vital Statistics. If these therapeutic complications and medical
      accidents were considered as a 'disease', they would rank as the 10th leading
      cause of death in New York City, surpassing homicides and suicides in some years.
      Nationwide policy shifts that use the term 'therapeutic complication' would
      improve the capture and reporting of these deaths, thus allowing better
      identification of fatal adverse medical events in order to focus on and assess
      preventative strategies.

PMID- 24679414
TI  - Neurotoxin-induced paralysis: a case of tick paralysis in a 2-year-old child.
AB  - BACKGROUND: Tick paralysis is an arthropod-transmitted disease causing
      potentially lethal progressive ascending weakness. The presenting symptoms of
      tick paralysis overlap those of acute inflammatory diseases of the peripheral
      nervous system and spinal cord; thus, the condition is often misdiagnosed,
      leading to unnecessary treatments and prolonged hospitalization. PATIENT: A 2
      year-old girl residing in northern New York and having no history of travel to
      areas endemic to ticks presented with rapidly progressing ascending paralysis,
      hyporeflexia, and intact sensory examination. Investigation included blood and
      serum toxicology screens, cerebrospinal fluid analysis, and brain imaging. With
      all tests negative, the child's condition was initially mistaken for botulism;
      however, an engorged tick was later found attached to the head skin. Following
      tick removal, the patient's weakness promptly improved with no additional
      interventions. CONCLUSION: Our patient illustrates the importance of thorough
      skin examination in all cases of acute progressive weakness and the necessity to
      include tick paralysis in the differential diagnosis of paralysis, even in
      nonendemic areas.

PMID- 24679415
TI  - [Meningitis after spinal anesthesia: think about bupivacaine!].

PMID- 24679416
TI  - Cenesthopathy in adolescence: an appraisal of diagnostic overlaps along the
      anxiety-hypochondriasis-psychosis spectrum.
AB  - OBJECTIVE: To discuss the diagnostic validity of unusual bodily perceptions along
      the spectrum from age-specific, often transitory and normal, to pathological
      phenomena in adolescence to hypochondriasis and finally to psychosis. METHODS:
      Critical literature review of the cornerstone diagnostic groups along the
      spectrum embracing anxiety and cenesthopathy in adolescence, hypochondriasis, and
      cenesthopathy and psychosis, followed by a discussion of the diagnostic overlaps
      along this spectrum. RESULTS: The review highlights significant overlaps between
      the diagnostic cornerstones. It is apparent that adolescents with unusual bodily
      perceptions may conceptually qualify for more than one diagnostic group along the
      spectrum. To determine whether cenesthopathies in adolescence mirror emerging
      psychosis, a number of issues need to be considered, i.e. age and mode of onset,
      gender, level of functioning and drug use. The role of overvalued ideas at the
      border between hypochondriasis and psychosis must be considered. CONCLUSION: As
      unusual bodily symptoms may in some instances meet formal psychosis risk
      criteria, a narrow understanding of these symptoms may lead to both inappropriate
      application of the new DSM-5 attenuated psychosis syndrome and of treatment
      selection. On the other hand, the possibility of a psychotic dimension of unusual
      bodily symptoms in adolescents must always be considered as most severe
      expression of the cenesthopathy spectrum.

PMID- 24679417
TI  - Anatomy and embryology of the biliary tract.
AB  - Working knowledge of extrahepatic biliary anatomy is of paramount importance to
      the general surgeon. The embryologic development of the extrahepatic biliary
      tract is discussed in this article as is the highly variable anatomy of the
      biliary tract and its associated vasculature. The salient conditions related to
      the embryology and anatomy of the extrahepatic biliary tract, including biliary
      atresia, choledochal cysts, gallbladder agenesis, sphincter of Oddi dysfunction,
      and ducts of Luschka, are addressed. 

PMID- 24679418
TI  - Biliary cysts: a review and simplified classification scheme.
AB  - Biliary cystic disease has been known of for centuries. It has traditionally been
      classified as 5 major types of disease, each with different clinical profiles and
      attributes. In this article, the basis for the existing classification schemes is
      reviewed and a simplified classification scheme and treatment regimen are
      suggested. 

PMID- 24679419
TI  - Symptomatic cholelithiasis and functional disorders of the biliary tract.
AB  - Symptomatic cholelithiasis and functional disorders of the biliary tract present
      with similar signs and symptoms. The functional disorders of the biliary tract
      include functional gallbladder disorder, dyskinesia, and the sphincter of Oddi
      disorders. Although the diagnosis and treatment of symptomatic cholelithiasis are
      relatively straightforward, the diagnosis and treatment of functional disorders
      can be much more challenging. Many aspects of the diagnosis and treatment of
      functional disorders are in need of further study. This article discusses
      uncomplicated gallstone disease and the functional disorders of the biliary tract
      to emphasize and update the essential components of diagnosis and management. 

PMID- 24679420
TI  - Gallstone pancreatitis: a review.
AB  - Gallstone disease is the most common cause of acute pancreatitis in the Western
      world. In most cases, gallstone pancreatitis is a mild and self-limiting disease,
      and patients may proceed without complications to cholecystectomy to prevent
      future recurrence. Severe disease occurs in about 20% of cases and is associated
      with significant mortality; meticulous management is critical. A thorough
      understanding of the disease process, diagnosis, severity stratification, and
      principles of management is essential to the appropriate care of patients
      presenting with this disease. This article reviews these topics with a focus on
      surgical management, including appropriate timing and choice of interventions. 

PMID- 24679421
TI  - Technical aspects of bile duct evaluation and exploration.
AB  - Choledocholithiasis is a common manifestation of biliary disease. Intraoperative
      cholangiography can be performed in several ways. Common bile duct exploration
      can be safely performed but necessitates an advanced level of surgical experience
      to limit complications and improve success. An algorithm based on available
      resources and the physician skill set is vital for safe and effective management
      of choledocholithiasis. Endoscopic retrograde cholangiopancreatography requires
      the availability of an advanced endoscopist as well as significant equipment and
      resources. Current training of young surgeons is limited for open biliary
      procedures and common bile duct explorations. Educational guidelines are
      necessary to reduce this educational gap. 

PMID- 24679422
TI  - Iatrogenic biliary injuries: identification, classification, and management.
AB  - Because it offers several advantages over open cholecystectomy, laparoscopic
      cholecystectomy has largely replaced open cholecystectomy for the management of
      symptomatic gallstone disease. The only potential disadvantage is a higher
      incidence of major bile duct injury. Although prevention of these biliary
      injuries is ideal, when they do occur, early identification and appropriate
      treatment are critical to improving the outcomes of patients suffering a major
      bile duct injury. This report delineates the key factors in classification (and
      its relationship to mechanism and management), identification (intraoperative and
      postoperative), and management principles of these bile duct injuries. 

PMID- 24679423
TI  - Proximal biliary tumors.
AB  - Cholangiocarcinoma is an uncommon tumor with a poor prognosis. Presenting
      symptoms are often nonspecific, and jaundice appears late in the disease course.
      Surgical resection and liver transplant are the potentially curative treatments.
      Palliation can be performed by percutaneous, endoscopic, or surgical
      interventions. 

PMID- 24679424
TI  - Distal cholangiocarcinoma.
AB  - Cholangiocarcinoma involving the distal common bile duct (distal
      cholangiocarcinoma [DCC]) is a periampullary neoplasm that is less common than,
      but often difficult to distinguish from, pancreatic adenocarcinoma (PDA). The
      prognosis and cure rate of DCC is improved over that of PDA, but it remains a
      highly lethal disease. Although the diagnostic and therapeutic management of DCC
      is not dissimilar from PDA, the pathophysiology is, in many instances, distinctly
      different. A multi-disciplinary approach toward DCC is important. 

PMID- 24679425
TI  - Gallbladder cancer.
AB  - Gallbladder cancer remains a relatively rare malignancy with a highly variable
      presentation. Gallbladder cancer is the most common biliary tract malignancy with
      the worst overall prognosis. With the advent of the laparoscope, in comparison
      with historical controls, this disease is now more commonly diagnosed
      incidentally and at an earlier stage. However, when symptoms of jaundice and pain
      are present, the prognosis remains dismal. From a surgical perspective,
      gallbladder cancer can be suspected preoperatively, identified intraoperatively,
      or discovered incidentally on final surgical pathology. 

PMID- 24679426
TI  - Bile metabolism and lithogenesis.
AB  - Our understanding of bile metabolism and the molecular effects of bile acids has
      expanded in recent years. Bile acids, which are classically recognized for their
      involvement in dietary lipid absorption, are now known to be involved in many
      aspects of energy metabolism and disease processes in humans. Cholelithiasis, a
      consequence of altered bile metabolism, affects a significant number of American
      adults. An understanding of the disease process, risk factors, and complications
      of gallbladder disease is necessary for the development of novel targeted
      treatments and prophylactic therapies against the development of gallstones. 

PMID- 24679427
TI  - Unusual complications of gallstones.
AB  - Extrinsic compression of the bile duct from gallstone disease is associated with
      bilio-biliary fistulization, requiring biliary-enteric reconstruction. Biliary
      enteric fistulas are associated with intestinal obstruction at various levels.
      The primary goal of therapy is relief of intestinal obstruction; definitive
      repair is performed for selected patients. Hemobilia from gallstone-related
      pseudoaneurysms is preferentially controlled by selective arterial embolization.
      Rapidly increasing jaundice with relatively normal liver enzymes is a diagnostic
      hallmark of bilhemia. Acquired thoraco-biliary fistulas are primarily treated by
      percutaneous and endoscopic interventions. 

PMID- 24679428
TI  - Endoscopic management of biliary disorders: diagnostic and therapeutic.
AB  - The use of peroral endoscopy in the diagnosis of and therapy for biliary
      disorders has evolved immensely since the introduction of flexible fiberoptic
      endoscopes more than 50 years ago. Endoscopic retrograde cholangiopancreatography
      was introduced approximately a decade after flexible upper endoscopy and has
      evolved from a purely diagnostic procedure to almost exclusively a therapeutic
      procedure for managing biliary tract disorders. Endoscopic ultrasound, which
      continues to be a procedure of high diagnostic yield, is becoming a therapeutic
      modality for management of biliary diseases. This article discusses the
      diagnostic and therapeutic aspects of endoscopic retrograde
      cholangiopancreatography and endoscopic ultrasound for evaluation and treatment
      of biliary diseases.

PMID- 24679429
TI  - Biliary issues in the bariatric population.
AB  - Biliary disease is common in the obese population and increases after bariatric
      surgery. This article reviews management of the gallbladder at the time of
      bariatric surgery, as well as imaging modalities in the bariatric surgery
      population and prevention of lithogenesis in the rapid weight loss phase. In
      addition, diagnosis and treatment options for biliary diseases are discussed,
      including laparoscopic-assisted percutaneous transgastric endoscopic retrograde
      cholangiopancreatography in the patient having bariatric surgery. 

PMID- 24679430
TI  - Technical aspects of cholecystectomy.
AB  - The gold standard for the surgical treatment of symptomatic cholelithiasis is
      conventional laparoscopic cholecystectomy (LC). Although it has been associated
      with a slightly higher incidence of bile duct injury (BDI) in comparison with
      open cholecystectomy (OC), LC is considered a very safe operation. Prevention of
      BDI should be routinely performed in every LC. Recent trends include the
      performance of cholecystectomy through a single incision and NOTES (Natural
      Orifice Transluminal Endoscopic Surgery). However, lack of evidence of clinical
      advantages prevents their widespread adoption, and more data are needed to assess
      whether their use is warranted. 

PMID- 24679431
TI  - Cholecystitis.
AB  - Acute cholecystitis is defined as inflammation of the gallbladder and is usually
      caused by obstruction of the cystic duct. Cholescintigraphy is the most sensitive
      imaging modality for cholecystitis. The gold standard treatment of acute
      cholecystitis is laparoscopic cholecystectomy. Operating early in the disease
      course decreases overall hospital stay and avoids increased complications,
      conversion to open procedures, and mortality. Cholecystitis during pregnancy is a
      challenging problem for surgeons. Operative intervention is generally safe for
      both mother and fetus, given the improved morbidity of the laparoscopic approach
      compared with open, although increased caution should be exercised in women with
      gallstone pancreatitis. 

PMID- 24679432
TI  - Small bowel and colon perforation.
AB  - For patients with small bowel and colonic perforations, a definitive diagnosis of
      the cause of perforation is not necessary before operation. Bowel obstruction and
      inflammatory bowel disease are the most common causes of nontraumatic intestinal
      perforations in industrialized countries, whereas infectious causes of intestinal
      perforations are more common in developing countries. Treatment of small bowel
      and colonic perforations generally includes intravenous antibiotics and fluid
      resuscitation, but the specific management of the bowel depends on the underlying
      cause of the perforation. 

PMID- 24679433
TI  - Biliary tract surgery.

PMID- 24679434
TI  - Biliary tract surgery.

PMID- 24679435
TI  - Potential role of selection bias in the association between childhood leukemia
      and residential magnetic fields exposure: a population-based assessment.
AB  - PURPOSE: Data from the Northern California Childhood Leukemia Study (NCCLS) were
      used to assess whether selection bias may explain the association between
      residential magnetic fields (assessed by wire codes) and childhood leukemia as
      previously observed in case-control studies. METHODS: Wiring codes were
      calculated for participating cases, n=310; and non-participating cases, n=66; as
      well as for three control groups: first-choice participating, n=174; first-choice
      non-participating, n=252; and replacement (non-first choice participating
      controls), n=220. RESULTS: Participating controls tended to be of higher
      socioeconomic status than non-participating controls, and lower socioeconomic
      status was related to higher wire-codes. The odds ratio (OR) for developing
      childhood leukemia associated with high wire-codes was 1.18 (95% CI: 0.85, 1.64)
      when all cases were compared to all first-choice controls (participating and non
      participating). The OR for developing childhood leukemia in the high current
      category was 1.43 (95% CI: 0.91, 2.26) when participating cases were compared to
      first-choice participating controls, but no associations were observed when
      participating cases were compared to non-participating controls (OR=1.06, 95% CI:
      0.71, 1.57) or to replacement controls (OR=1.06, 95% CI: 0.71, 1.60).
      CONCLUSIONS: The observed risk estimates vary by type of control group, and no
      statistically significant association between wire codes and childhood leukemia
      is observed in the California population participating in the NCCLS.

PMID- 24679437
TI  - Bias in chemokine receptor signalling.
AB  - Chemokine receptors are widely expressed on a variety of immune cells and play a
      crucial role in normal physiology as well as in inflammatory and infectious
      diseases. The existence of 23 chemokine receptors and 48 chemokine ligands
      guarantees a tight control and fine-tuning of the immune system. Here, we discuss
      the multiple regulatory mechanisms of chemokine signalling at a systemic,
      cellular, and molecular level. In particular, we focus on the impact of biased
      signalling at the receptor level; an emerging concept in molecular pharmacology.
      An improved understanding of these mechanisms may provide a framework for more
      effective drug discovery and development at a target class that is so relevant
      for immune function. 

PMID- 24679436
TI  - The establishment of B versus T cell identity.
AB  - In B cell progenitors, E-proteins E2A and HEB (HeLa E-box binding protein) are
      crucial for the induction of a B lineage-specific program of gene expression and
      for orchestrating the assembly of the immunoglobulin loci. In the thymus E2A and
      HEB act differently, activating the expression of genes closely associated with
      the establishment of T cell identity and promoting the rearrangement of T cell
      receptor (TCR) loci. These findings have raised the question as to how E-proteins
      exert these different activities. We review here the distinct regulatory networks
      that establish B versus T cell identity, and how genomic architecture and
      location of genes is modulated in these lineage decisions. We conclude by
      proposing a model wherein stochasticity in the nuclear location of the early B
      cell factor 1 (Ebf1) locus in multipotent progenitors determines this lineage
      choice. 

PMID- 24679438
TI  - Choice of operating voltage for a transmission electron microscope.
AB  - An accelerating voltage of 100-300kV remains a good choice for the majority of
      TEM or STEM specimens, avoiding the expense of high-voltage microscopy but
      providing the possibility of atomic resolution even in the absence of lens
      aberration correction. For specimens thicker than a few tens of nm, the image
      intensity and scattering contrast are likely to be higher than at lower voltage,
      as is the visibility of ionization edges below 1000eV (as required for EELS
      elemental analysis). In thick (>100nm) specimens, higher voltage ensures less
      beam broadening and better spatial resolution for STEM imaging and EDX
      spectroscopy. Low-voltage (e.g. 30kV) TEM or STEM is attractive for a very thin
      (e.g. 10nm) specimen, as it provides higher scattering contrast and fewer
      problems for valence-excitation EELS. Specimens that are immune to radiolysis
      suffer knock-on damage at high current densities, and this form of radiation
      damage can be reduced or avoided by choosing a low accelerating voltage. Low
      voltage STEM with an aberration-corrected objective lens (together with a high
      angle dark-field detector and/or EELS) offers atomic resolution and elemental
      identification from very thin specimens. Conventional TEM can provide atomic
      resolution in low-voltage phase-contrast images but requires correction of
      chromatic aberration and preferably an electron-beam monochromator. Many non
      conducting (e.g. organic) specimens damage easily by radiolysis and radiation
      damage then determines the TEM image resolution. For bright-field scattering
      contrast, low kV can provide slightly better dose-limited resolution if the
      specimen is very thin (a few nm) but considerably better resolution is possible
      from a thicker specimen, for which higher kV is required. Use of a phase plate in
      a conventional TEM offers the most dose-efficient way of achieving atomic
      resolution from beam-sensitive specimens. 

PMID- 24679439
TI  - Exploring the interface between diagnostics and maps of neglected parasitic
      diseases.
AB  - Although not new, the 'One Health' concept is gaining progressively more
      importance in parasitology. Now more than ever, veterinary and human perspectives
      should be closely joined in diagnosis and surveillance of neglected parasitic
      diseases. We argue that concerted, standardized and harmonized diagnostic and
      surveillance strategies are needed for the control and/or elimination of animal
      and human neglected parasitic infections. A key challenge is to integrate
      parasitological data with available geospatial methods in an accessible and user
      friendly framework. We discuss the capability of new diagnostic devices (e.g.
      Mini-FLOTAC) and geospatial technologies supported by mobile- and electronic
      based approaches as one of the research priorities of the new millennium.

PMID- 24679440
TI  - CT screening in COPD: impact on lung cancer mortality: de Torres JP, Casanova C,
      Marin JM et al. Exploring the impact of screening with low-dose CT on lung cancer
      mortality in mild to moderate COPD patients: a pilot study. Respir med 2013; 107:
      702-707.

PMID- 24679441
TI  - Anti-inflammatory components of Euphorbia humifusa Willd.
AB  - Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester
      (2), along with 24 known compounds (3-26) were isolated from Euphorbia humifusa
      Willd. The effects of these compounds on soluble epoxide hydrolase (sEH)
      inhibitory activity were evaluated. Flavonoid compounds (10-21) exhibited high
      sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited
      sEH enzymatic activity, with IC50 values as low as 18.05+/-1.17, 18.64+/-1.83,
      and 17.23+/-0.84 MUM, respectively. In addition, the effects of these compounds
      on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor
      alpha (TNF-alpha) production by RAW 264.7 cells were investigated. Compounds 3-6,
      8, 18, 20-23, and 25-26 inhibited the production of both NO and TNF-alpha, with
      IC50 values ranging from 11.1+/-0.9 to 45.3+/-1.6 MUM and 14.4+/-0.5 to 44.5+/
      1.2 MUM, respectively.

PMID- 24679442
TI  - Quantitative optical coherence tomography angiography of choroidal
      neovascularization in age-related macular degeneration.
AB  - PURPOSE: To detect and quantify choroidal neovascularization (CNV) in patients
      with age-related macular degeneration (AMD) using optical coherence tomography
      (OCT) angiography. DESIGN: Observational, cross-sectional study. PARTICIPANTS: A
      total of 5 normal subjects and 5 subjects with neovascular AMD were included.
      METHODS: A total of 5 eyes with neovascular AMD and 5 normal age-matched controls
      were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept
      source OCT. The macular angiography scan covered a 3 * 3-mm area and comprised
      200 * 200 * 8 A-scans acquired in 3.5 seconds. Flow was detected using the split
      spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts
      were removed by 3-dimensional (3D) orthogonal registration and merging of 4
      scans. The 3D angiography was segmented into 3 layers: inner retina (to show
      retinal vasculature), outer retina (to identify CNV), and choroid. En face
      maximum projection was used to obtain 2-dimensional angiograms from the 3 layers.
      The CNV area and flow index were computed from the en face OCT angiogram of the
      outer retinal layer. Flow (decorrelation) and structural data were combined in
      composite color angiograms for both en face and cross-sectional views. MAIN
      OUTCOME MEASURES: The CNV angiogram, CNV area, and CNV flow index. RESULTS: En
      face OCT angiograms of CNV showed sizes and locations that were confirmed by
      fluorescein angiography (FA). Optical coherence tomography angiography provided
      more distinct vascular network patterns that were less obscured by subretinal
      hemorrhage. The en face angiograms also showed areas of reduced choroidal flow
      adjacent to the CNV in all cases and significantly reduced retinal flow in 1
      case. Cross-sectional angiograms were used to visualize CNV location relative to
      the retinal pigment epithelium and Bruch's layer and classify type I and type II
      CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were
      associated with larger CNV and type II CNV. CONCLUSIONS: Optical coherence
      tomography angiography provides depth-resolved information and detailed images of
      CNV in neovascular AMD. Quantitative information regarding CNV flow and area can
      be obtained. Further studies are needed to assess the role of quantitative OCT
      angiography in the evaluation and treatment of neovascular AMD.

PMID- 24679443
TI  - Polymorphism in THBS1 gene is associated with post-refractive surgery chronic
      ocular surface inflammation.
AB  - PURPOSE: To determine the association of single nucleotide polymorphisms (SNPs)
      of the thrombospondin 1 (THBS1) gene with development of chronic ocular surface
      inflammation (keratoconjunctivitis) after refractive surgery. DESIGN:
      Retrospective cohort study. PARTICIPANTS: Active duty U.S. Army soldiers (n =
      143) who opted for refractive surgery. METHODS: Conjunctival impression cytology
      samples collected from participants before the surgery were used to harvest DNA
      for genotyping 5 THBS1 SNPs (rs1478604, rs2228262, rs2292305, rs2228262, and
      rs3743125) using the Sequenom iPLEX Gold platform (Sequenom, San Diego, CA).
      Samples collected after surgery were used to harvest RNA for gene expression
      analysis by real-time polymerase chain reaction (PCR). Participants were followed
      for 1 year after surgery to monitor the status of keratoconjunctivitis. MAIN
      OUTCOME MEASURES: Genetic basis of the development of chronic
      keratoconjunctivitis after refractive surgery. RESULTS: Carriers of minor alleles
      of 3 SNPs each were found to be more susceptible to developing chronic
      keratoconjunctivitis (rs1478604: odds ratio [OR], 2.5; 95% confidence interval
      [CI], 1.41-4.47; P = 2.5 * 10(-3); rs2228262 and rs2292305: OR, 1.9; 95% CI, 1.05
      3.51; P = 4.8 * 10(-2)). Carriers of the rs1478604 minor allele expressed
      significantly reduced levels of thrombospondin 1 (TSP1) (P = 0.042) and increased
      levels of an inflammatory cytokine associated with keratoconjunctivitis,
      interleukin-1beta (P = 0.025), in their ocular surface epithelial cells compared
      with homozygous major allele controls. CONCLUSIONS: Genetic variation in the
      THBS1 gene that results in decreased expression of the encoded glycoprotein TSP1
      in ocular surface epithelial cells significantly increases the susceptibility to
      develop chronic ocular surface inflammation after refractive surgery. Further
      investigation of THBS1 SNPs in a larger sample size is warranted.

PMID- 24679444
TI  - Intravitreal aflibercept injection for macular edema due to central retinal vein
      occlusion: two-year results from the COPERNICUS study.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal aflibercept
      injection (IAI) for the treatment of macular edema secondary to central retinal
      vein occlusion (CRVO). DESIGN: Randomized, double-masked, phase 3 trial.
      PARTICIPANTS: A total of 188 patients with macular edema secondary to CRVO.
      METHODS: Patients received IAI 2 mg (IAI 2Q4) (n = 114) or sham injections (n =
      74) every 4 weeks up to week 24. During weeks 24 to 52, patients from both arms
      were evaluated monthly and received IAI as needed, or pro re nata (PRN) (IAI 2Q4
      + PRN and sham + IAI PRN). During weeks 52 to 100, patients were evaluated at
      least quarterly and received IAI PRN. MAIN OUTCOME MEASURES: The primary efficacy
      end point was the proportion of patients who gained >= 15 letters in best
      corrected visual acuity (BCVA) from baseline to week 24. This study reports week
      100 results. RESULTS: The proportion of patients gaining >= 15 letters was 56.1%
      versus 12.3% (P<0.001) at week 24, 55.3% versus 30.1% (P<0.001) at week 52, and
      49.1% versus 23.3% (P<0.001) at week 100 in the IAI 2Q4 + PRN and sham + IAI PRN
      groups, respectively. The mean change from baseline BCVA was also significantly
      higher in the IAI 2Q4 + PRN group compared with the sham + IAI PRN group at week
      24 (+17.3 vs. -4.0 letters; P<0.001), week 52 (+16.2 vs. +3.8 letters; P<0.001),
      and week 100 (+13.0 vs. +1.5 letters; P<0.0001). The mean reduction from baseline
      in central retinal thickness was 457.2 versus 144.8 MUm (P<0.001) at week 24,
      413.0 versus 381.8 MUm at week 52 (P = 0.546), and 390.0 versus 343.3 MUm at week
      100 (P = 0.366) in the IAI 2Q4 + PRN and sham + IAI PRN groups, respectively. The
      mean number (standard deviation) of PRN injections in the IAI 2Q4 + PRN and sham
      + IAI PRN groups was 2.7 +/- 1.7 versus 3.9 +/- 2.0 during weeks 24 to 52 and 3.3
      +/- 2.1 versus 2.9 +/- 2.0 during weeks 52 to 100, respectively. The most
      frequent ocular serious adverse event from baseline to week 100 was vitreous
      hemorrhage (0.9% vs. 6.8% in the IAI 2Q4 + PRN and sham + IAI PRN groups,
      respectively). CONCLUSIONS: The visual and anatomic improvements after fixed
      dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52
      were diminished after continued PRN dosing, with a reduced monitoring frequency
      from weeks 52 to 100.

PMID- 24679445
TI  - [Clostridium difficile infections in Spanish Internal Medicine departments during
      the period 2005-2010: the burden of the disease].
AB  - INTRODUCTION: Clostridium Difficile infection (CDI) is increasing in Spain. A
      review is presented of this infection in order to evaluate the burden of the
      disease in this country. MATERIAL: An analytical retrospective and descriptive
      study was conducted by analyzing the Minimum Basic Data Set of patients admitted
      to Internal Medicine Departments and with and without CDI between the years 2005
      2010. Clinical and demographical variables were compared. RESULTS: Mean age was
      75.5 years (SD 15.4), 54.9% were women and mean stay was 22.2 days (SD 24.8). The
      Cost [(? 5,001 (SD 4,985) vs [? 3,934 (SD 2,738)] and diagnostic complexity [2.04
      (SD 2.62) vs [1.67 (SD 1.47)] were also different. Mortality for all causes was
      12.5% vs 9.8%. Death risk showed a 30% increase (odds ratio 1.30, 95% confidence
      interval;1.21-1.39) and readmission rate was 30.4% vs 13.5%. Distribution of
      cases showed season variations (more cases in winter), and annual incidence
      increased during the study period. Comorbidities associated to increased risk of
      acquiring CDI were: anemia, human immunodeficiency virus, dementia, malnutrition,
      chronic renal failure, and living in a nursing home. CONCLUSION: The results
      showed a clear negative impact of CDI on hospital admissions. A trend towards
      progression in its incidence without changes in mortality or readmission rates
      was observed, in common with the rest of Europe and the Western World.

PMID- 24679446
TI  - [Analysis of co-infections between influenza A and influenza B viruses and other
      respiratory viruses, 2012-2013].

PMID- 24679447
TI  - [Epidemiology of hospitalizations for tuberculosis in Spain: analysis of minimum
      data set 1999-2009].
AB  - INTRODUCTION: The National Hospital Discharge Registry is a clinical
      administrative database on hospital discharges, which is very useful at a
      regional level as a complementary source for surveillance. There are few national
      studies on tuberculosis (TB) using the National Hospital Discharge Registry, thus
      it was considered of interest to study the characteristics and trends of hospital
      discharges for TB in Spain. METHODS: A descriptive study was performed using the
      main variables in the National Hospital Discharge Registry (sex, age, main
      diagnosis, type of discharge, length of stay), and trend analysis of
      hospitalization rates per 100,000 population, as well as primary diagnosis, by
      sex, age group, and type of TB (pulmonary [TBP]/extrapulmonary [TBEP]), for the
      period 1999-2009 in Spain. RESULTS: A total of 65,609 hospital discharges were
      included in the study (66% male, 66% TBP, and 52% between 15-44 years). The
      overall rate of TB for the entire hospitalization period was 13.93 per 100,000
      inhabitants, being 18.83 in males and 9.18 in females. The hospitalization rates
      for TBP and TBEP decreased in the period 1999-2009 in both sexes (TBP in males,
      from 18 to 13, and in females, from 8 to 6; TBEP in males from 4 to 3, and from 3
      to 2 in female hospitalizations/100,000 habitants). In TBP, children are those
      with a smallest decline, and in TBEP there is an increase in males in all age
      groups from 2005. CONCLUSIONS: The results are consistent with those from
      surveillance. The slow decline in rates in children and the increase in
      extrapulmonary forms in males may be related to immigration, so it is necessary
      to improve TB monitoring in these groups.

PMID- 24679448
TI  - [The need for a consensus on human immunodeficiency virus screening and diagnosis
      in emergency departments].

PMID- 24679449
TI  - Effect of fertility on the economics of pasture-based dairy systems.
AB  - There are significant costs associated with reproductive inefficiency in pasture
      based dairy herds. This study has quantified the economic effect of a number of
      key variables associated with reproductive inefficiency in a dairy herd and
      related them to 6-week calving rate for both cows and heifers. These variables
      include: increased culling costs, the effects of sub optimum calving dates,
      increased labour costs and increased artificial insemination (AI) and
      intervention costs. The Moorepark Dairy Systems Model which is a stochastic
      budgetary simulation model was used to simulate the overall economic effect at
      farm level. The effect of change in each of the components was simulated in the
      model and the costs associated with each component was quantified. An analysis of
      national data across a 4-year period using the Irish Cattle Breeding Federation
      database was used to quantify the relationship between the 6-week calving rate of
      a herd with survivability (%), calving interval (days) and the level of AI usage.
      The costs associated with increased culling (%), calving date slippage (day),
      increased AI and intervention costs (0.1 additional inseminations), as well as,
      increased labour costs (10%) were quantified as ?13.68, ?3.86, ?4.56 and
      ?29.6/cow per year. There was a statistically significant association between the
      6-week calving rate and survivability, calving interval and AI usage at farm
      level. A 1% change in 6-week calving rate was associated with ?9.26/cow per annum
      for cows and ?3.51/heifer per annum for heifers. This study does not include the
      indirect costs such as reduced potential for expansion, increased costs
      associated with failing to maintain a closed herd as well as the unrealised
      potential within the herd. 

PMID- 24679450
TI  - [Selective laser trabeculoplasty: results after a first and a second session,
      overall comparison and results for three indications].
AB  - PURPOSE: To compare the results obtained with SLT trabeculoplasty after an
      initial treatment (SLT-1) and after a second treatment (SLT-2). Subgroup analysis
      according to trabecular pigmentation and the existence of a high myopia.
      MATERIALS AND METHODS: Retrospective study of 77 patients, 152 SLT sessions
      performed in the Ophthalmology Department of Clermont-Ferrand University Medical
      Center, 118 SLT-1, 34 SLT-2. Three comparable groups of patients were assembled:
      group 1 (glaucoma patients with normal or subnormal trabecular pigmentation),
      group 2 (glaucoma patients with high myopia), and group 3 (glaucoma patients with
      significant trabecular pigmentation). The results were compared between groups,
      for SLT-1 and SLT-2. RESULTS: Intraocular pressure lowering was consistent with
      data reported in the literature. Comparison of the results of SLT-1 versus SLT-2
      did not find any significant difference in terms of IOP change. However, after
      SLT-2, the IOP response appears significantly greater (P=0.03) in the group with
      significant trabecular pigmentation compared to the non-myopic group with normal
      trabecular pigmentation. DISCUSSION: Our results are consistent with the
      literature for efficacy, tolerance and reproducibility of SLT. No reduction in
      SLT efficacy was observed after a second session. Trabecular pigmentation is not
      a predictor of the response after the first session. In the case of retreatment
      (SLT-2), the differences observed lead to the hypothesis that it may be
      appropriate to perform at least two SLT treatments in patients with significant
      trabecular pigmentation in order to obtain maximal effect. Myopia, a variable not
      previously studied, does not seem to influence SLT outcomes. CONCLUSION:
      Trabecular pigmentation and the presence of myopia do not appear to be predictive
      of a successful first treatment. However, our study leads us to suggest the
      hypothesis that the maximal response of SLT in patients with significant
      trabecular pigmentation is not obtained until after at least two sessions. This
      observation opens an interesting perspective on the therapeutic strategy to adopt
      in the case of pigmentary glaucoma.

PMID- 24679451
TI  - Comparison of transepithelial corneal collagen crosslinking with epithelium-off
      crosslinking in progressive keratoconus.
AB  - PURPOSE: To evaluate the safety and efficacy of transepithelial corneal collagen
      crosslinking (TE-CXL) as compared to epithelium-off crosslinking (epi-off CXL) in
      progressive keratoconus. METHODS: Records of keratoconus patients treated with TE
      CXL or epi-off CXL were reviewed retrospectively. Patients were included if they
      had at least 12months follow-up. Pre- and postoperative measurements of visual
      acuity, refractive errors, keratometry, corneal topography and pachymetry were
      assessed and compared. RESULTS: There was no statistically significant difference
      between two groups at baseline in terms of demographic, refractive and corneal
      parameters. Mean maximum cone apex curvature (apical K) increased from 51.62+/-5.
      Eighty-four diopters (D) to 53.70+/-5.49 D in the TE-CXL group (n=17), and
      decreased from 52.02+/-4.07 D to 51.22+/-3.51 in the epi-off CXL group (n=19) at
      the end of the follow-up period. The difference between two groups was
      statistically significant (P=0.0002). An increase of>=1D in apical K was observed
      in two of 19 eyes (11%) in the epi-off CXL group, and 11 of 17 eyes (65%) in TE
      CXL group at the last follow-up visit, compared to baseline (P<0.0001). Fourteen
      patients in the epi-off CXL group exhibited corneal edema that resolved without
      haze with topical corticosteroid treatment by 4months. No postoperative corneal
      edema was observed in TE-CXL group. CONCLUSIONS: Although it is safe and well
      tolerated, TE-CXL does not effectively halt the progression of keratoconus. Epi
      off CXL appears to be effective in stopping progression and even improves corneal
      parameters.

PMID- 24679452
TI  - [Treatment of retinoblastoma: Senegalese experience].
AB  - INTRODUCTION: Retinoblastoma is a malignant tumor arising from retinal stem cells
      or retinoblasts. Its management has been well determined. The goal of this study
      is to report preliminary results obtained with combined chemotherapy and surgical
      treatment. PATIENTS AND METHODS: Our transverse prospective study includes
      retinoblastomas diagnosed and treated on our service from January 2006 to
      December 2010. Fundus examination under general anesthesia and radiological
      examination, orbital/brain CT or if unavailable, ultrasound, were systematically
      performed. MRI was able to be obtained in one case. The patients received 6
      courses of chemotherapy (vincristin-carboplatin-etoposide or vincristin
      cyclophosphamide), including 2 preoperative courses and 4 postoperative courses.
      A surgical procedure (enucleation or exenteration) supplemented the treatment,
      followed by histologic analysis of the specimen. External radiation therapy and
      conservative management were not available. RESULTS: Fifty-nine patients were
      treated. Median age at time of diagnosis was 9months (range 2months to 7years);
      the gender ratio was 1.18. Tumors were bilateral in 12 cases and unilateral in 47
      cases, intraocular in 34 cases and extraocular in 25 cases. Optic nerve
      involvement was confirmed by histology in 12 cases. Twenty-one patients died from
      recurrence and/or metastatic disease, or during chemotherapy. Seven were lost to
      follow-up, and 31 have survived uneventfully. DISCUSSION: Improvement of
      mortality is still our major concern. Radiation therapy is essential in the
      presence of optic nerve involvement. CONCLUSION: Long-term survival will
      determine the efficacy of this form of management. The contribution of new
      therapeutic means will improve these results.

PMID- 24679453
TI  - Manipulating mitochondrial genomes in the clinic: playing by different rules.
AB  - Recently, several publications have surfaced describing methods to manipulate
      mitochondrial genomes in tissues and embryos. With them, a somewhat
      sensationalistic uproar about the generation of children with 'three parents' has
      dominated the discussion in the lay media. It is important that society
      understands the singularities of mitochondrial genetics to judge these procedures
      in a rational light, so that this ongoing discussion does not preclude the
      helping of patients and families harboring mutated mitochondrial genomes. 

PMID- 24679454
TI  - A survey of biosecurity-related practices, opinions and communications across
      dairy farm veterinarians and advisors.
AB  - Biosecurity at farm-level can often be poorly implemented, and lack of
      information has been cited by many studies as a potential explanation. Veterinary
      practitioners (VPs) and dairy advisors (DAs) play a central role in the provision
      of animal health and management services to dairy farmers. The objective of this
      study was to document and compare biosecurity-related practices and opinions
      across VPs and DAs in Ireland. A selection of veterinary experts (VEs) from
      outside of Ireland was also surveyed. Questionnaires were completed and response
      rates of 47% (VPs), 97% (DAs), and 65% (VEs) were achieved. Significant
      differences were identified in the promotion and implementation of biosecurity
      between VPs and DAs, with a higher proportion of VPs regularly receiving requests
      from (P = 0.004), and dispensing advice to (P < 0.0001), their farm clients.
      Communication between DAs and VPs was sub-optimal with over 60% of each group not
      in regular communication with each other. With regard to the main farmer
      motivation for biosecurity implementation, the majority of VPs (62%) prioritised
      external factors such as 'economic benefit' and 'mandatory obligation', while the
      majority of DAs prioritised health/animal-related factors (69%), which were
      similar to those of farmers (83.1%), although they remained significantly less
      likely (OR = 1.8) than farmers to choose such motivators (P = 0.005).
      Inconsistencies in the implementation of, and in opinions relating to, farm
      biosecurity were highlighted across all the groups surveyed emphasising the need
      for standardised information and improved communication.

PMID- 24679455
TI  - Equine insect bite hypersensitivity: are molecular diagnostic tests the future?

PMID- 24679456
TI  - Effects of opioids on phagocytic function, oxidative burst capacity, cytokine
      production and apoptosis in canine leukocytes.
AB  - Opioids alter immune and apoptotic pathways in several species. They are commonly
      used in companion animals affected with infectious and/or inflammatory disease,
      but the immunomodulatory and apoptotic effects of these drugs in dogs are
      relatively unknown. The aim of the present study was to evaluate the effects of
      morphine, buprenorphine and fentanyl on canine phagocyte function, oxidative
      burst capacity, leukocyte cytokine production, and lymphocyte apoptosis. Blood
      from six healthy adult dogs was incubated in the presence or absence of morphine
      (200 ng/mL), buprenorphine (10 ng/mL) or fentanyl (10 ng/mL) for 3 h (phagocytic
      function; cytokine production) or 8 h (apoptosis). Neutrophil phagocytosis of
      opsonized Escherichia coli, respiratory burst capacity after stimulation with
      opsonized E. coli or phorbol 12-myristate 13-acetate (PMA), and Annexin V-FITC
      staining of apoptotic lymphocytes were evaluated using flow cytometry. Leukocyte
      production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10 was
      assessed after incubation with lipopolysaccharide (LPS), lipoteichoic acid (LTA)
      or peptidoglycan. Morphine promoted a more intense respiratory burst. Morphine,
      buprenorphine and fentanyl all promoted LPS- or LTA-induced TNF-alpha and IL-10
      production. However, the opioids tested did not alter TNF-alpha:IL-10 ratios.
      Morphine, buprenorphine and fentanyl all inhibited neutrophil apoptosis, an
      effect that was not concentration dependent in nature. These data indicate that
      opioids alter immune and apoptotic pathways in dogs. The possible effects of
      opioids on immune and cellular responses should be considered when designing
      studies and interpreting outcomes of studies involving administration of opioids
      in dogs.

PMID- 24679457
TI  - Estimates of genetic parameters of distal limb fracture and superficial digital
      flexor tendon injury in UK Thoroughbred racehorses.
AB  - A retrospective cohort study of distal limb fracture and superficial digital
      flexor tendon (SDFT) injury in Thoroughbred racehorses was conducted using health
      records generated by the British Horseracing Authority (BHA) between 2000 and
      2010. After excluding records of horses that had both flat and jump racing
      starts, repeated records were reduced to a single binary record per horse (n =
      66,507, 2982 sires), and the heritability of each condition was estimated using
      residual maximum likelihood (REML) with animal logistic regression models.
      Similarly, the heritability of each condition was estimated for the flat racing
      and jump racing populations separately. Bivariate mixed models were used to
      generate estimates of genetic correlations between SDFT injury and distal limb
      fracture. The heritability of distal limb fracture ranged from 0.21 to 0.37. The
      heritability of SDFT injury ranged from 0.31 to 0.34. SDFT injury and distal limb
      fracture were positively genetically correlated. These findings suggest that
      reductions in the risk of the conditions studied could be attempted using
      targeted breeding strategies.

PMID- 24679458
TI  - Development of a method for isolating bovine colostrum mononuclear leukocytes for
      phenotyping and functional studies.
AB  - The present study reports a method for isolating bovine colostrum mononuclear
      cells (CMC) for phenotyping and functional studies. As well as being an important
      source of immunoglobulins, colostrum also contains leukocytes that may be of
      greater importance for passive immunity than has previously been thought.
      Different protocols have been reported for isolating leukocytes from bovine
      colostrum, although none of these have been validated, and phenotypic analysis of
      cell populations has not always been performed. In this study, bovine CMC were
      isolated by density gradient centrifugation. Cell populations were identified by
      flow cytometry using antibodies against selected bovine cell surface markers and
      the proliferative capacity of these cells was determined using a (3)H-thymidine
      proliferation assay. The mean cell count of isolated CMC was 3 * 10(4) and 1 *
      10(5) per mL colostrum for the samples used in the flow cytometric assay and the
      proliferation assay, respectively. A mean of 25.4 +/- 17.1% CMC were identified
      as T lymphocytes, 2.9 +/- 3.0% as B lymphocytes and 32.7 +/- 13.7% as
      macrophages. In terms of proliferation, the mean counts per minute were 4.3 *
      10(3) and 1.8 * 10(4) for cells cultured in medium only or in the presence of
      concanavalin A, respectively, showing that CMC are viable and capable of
      responding to mitogen stimulation. Isolation of CMC and the subsequent phenotypic
      analysis of the different subpopulations were repeatable, with agreement indices
      varying between 0.5 and 1.0. Agreement indices for the proliferation assay were
      estimated at 0.8.

PMID- 24679459
TI  - A Virtual Week study of prospective memory function in autism spectrum disorders.
AB  - Prospective memory (PM) refers to the implementation of delayed intentions, a
      cognitive ability that plays a critical role in daily life because of its
      involvement in goal-directed behavior and consequently the development and
      maintenance of independence. Emerging evidence indicates that PM may be disrupted
      in autism spectrum disorders (ASDs), potentially contributing to the functional
      difficulties that characterize this group. However, the degree, nature, and
      specificity of ASD-related impairment remains poorly understood. In the current
      study, children between 8 and 12 years of age who were diagnosed with ASDs (n=30)
      were compared with typically developing children (n=30) on a child-appropriate
      version of the Virtual Week board game. This measure provides an opportunity to
      investigate the different sorts of PM failures that occur. The ASD group showed
      significant PM impairment on measures of time-based (but not event-based)
      prospective remembering. However, only a subtle difference emerged between
      regular and irregular PM tasks, and group differences were consistent across
      these tasks. Because regular and irregular tasks differentially load
      retrospective memory, these data imply that the PM difficulties seen in ASDs may
      primarily reflect a monitoring deficit and not an encoding and memory storage
      deficit. PM performance was poorer under conditions of high ongoing task
      absorption, but the magnitude of this effect did not vary as a function of group.
      In both groups, time-based (but not event-based) PM difficulties were associated
      with functional outcomes in daily life, but only an inconsistent association with
      executive control emerged.

PMID- 24679460
TI  - George Russell Prout Jr., M.D., 1924-2013, founding editor, urologic oncology.

PMID- 24679461
TI  - Incorporating biomarker research in a real-world setting: challenges of a
      prophecy.

PMID- 24679462
TI  - Commentary on "Postoperative radiotherapy after radical prostatectomy for high
      risk prostate cancer: long-term results of a randomised controlled trial (EORTC
      trial 22911)." Bolla M, van Poppel H, Tombal B, Vekemans K, Da Pozzo L, de Reijke
      TM, Verbaeys A, Bosset JF, van Velthoven R, Colombel M, van de Beek C, Verhagen
      P, van den Bergh A, Sternberg C, Gasser T, van Tienhoven G, Scalliet P,
      Haustermans K, Collette L; European Organisation for Research and Treatment of
      Cancer, Radiation Oncology and Genito-Urinary Groups. Department of Radiation
      Oncology, Centre Hospitalier Universitaire A Michallon, Grenoble, France.: Lancet
      2012;380(9858):2018-27. doi: 10.1016/S0140-6736(12)61253-7. [Epub 2012 Oct 19].
AB  - BACKGROUND: We report the long-term results of a trial of immediate postoperative
      irradiation versus a wait-and-see policy in patients with prostate cancer
      extending beyond the prostate, to confirm whether previously reported progression
      free survival was sustained. METHODS: This randomised, phase 3, controlled trial
      recruited patients aged 75 years or younger with untreated cT0-3 prostate cancer
      (WHO performance status 0 or 1) from 37 institutions across Europe. Eligible
      patients were randomly assigned centrally (1:1) to postoperative irradiation (60
      Gy of conventional irradiation to the surgical bed for 6 weeks) or to a wait-and
      see policy until biochemical progression (increase in prostate-specific
      antigen>0.2 MUg/L confirmed twice at least 2 weeks apart). We analysed the
      primary endpoint, biochemical progression-free survival, by intention to treat
      (two-sided test for difference at alpha = 0.05, adjusted for one interim
      analysis) and did exploratory analyses of heterogeneity of effect. This trial is
      registered with ClinicalTrials.gov, number NCT00002511. FINDINGS: 1005 patients
      were randomly assigned to a wait-and-see policy (n = 503) or postoperative
      irradiation (n = 502) and were followed up for a median of 10.6 years (range 2
      months to 16.6 years). Postoperative irradiation significantly improved
      biochemical progression-free survival compared with the wait-and-see policy (198
      [39.4%] of 502 patients in postoperative irradiation group vs 311 [61.8%] of 503
      patients in wait-and-see group had biochemical or clinical progression or died;
      HR 0.49 [95% CI 0.41-0.59]; p<0.0001). Late adverse effects (any type of any
      grade) were more frequent in the postoperative irradiation group than in the wait
      and-see group (10 year cumulative incidence 70.8% [66.6-75.0] vs 59.7% [55.3
      64.1]; p = 0.001). INTERPRETATION: Results at median follow-up of 10.6 years show
      that conventional postoperative irradiation significantly improves biochemical
      progression-free survival and local control compared with a wait-and-see policy,
      supporting results at 5 year follow-up; however, improvements in clinical
      progression-free survival were not maintained. Exploratory analyses suggest that
      postoperative irradiation might improve clinical progression-free survival in
      patients younger than 70 years and in those with positive surgical margins, but
      could have a detrimental effect in patients aged 70 years or older. FUNDING:
      Ligue Nationale contre le Cancer (Comite de l'Isere, Grenoble, France) and the
      European Organisation for Research and Treatment of Cancer (EORTC) Charitable
      Trust.

PMID- 24679463
TI  - Commentary on "Patient-reported outcomes after 3-dimensional conformal, intensity
      modulated, or proton beam radiotherapy for localized prostate cancer." Gray PJ,
      Paly JJ, Yeap BY, Sanda MG, Sandler HM, Michalski JM, Talcott JA, Coen JJ,
      Hamstra DA, Shipley WU, Hahn SM, Zietman AL, Bekelman JE, Efstathiou JA. Harvard
      Radiation Oncology Program, Boston, MA.: Cancer 2013;119(9):1729-35. doi:
      10.1002/cncr.27956. [Epub 2013 Feb 22].
AB  - BACKGROUND: Recent studies have suggested differing toxicity patterns for
      patients with prostate cancer who receive treatment with 3-dimensional conformal
      radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam
      therapy (PBT). METHODS: The authors reviewed patient-reported outcomes data
      collected prospectively using validated instruments that assessed bowel and
      urinary quality of life (QOL) for patients with localized prostate cancer who
      received 3DCRT (n = 123), IMRT (n = 153) or PBT (n = 95). Clinically meaningful
      differences in mean QOL scores were defined as those exceeding half the standard
      deviation of the baseline mean value. Changes from baseline were compared within
      groups at the first post-treatment follow-up (2-3 months from the start of
      treatment) and at 12 months and 24 months. RESULTS: At the first post-treatment
      follow-up, patients who received 3DCRT and IMRT, but not those who received PBT,
      reported a clinically meaningful decrement in bowel QOL. At 12 months and 24
      months, all 3 cohorts reported clinically meaningful decrements in bowel QOL.
      Patients who received IMRT reported clinically meaningful decrements in the
      domains of urinary irritation/obstruction and incontinence at the first post
      treatment follow-up. At 12 months, patients who received PBT, but not those who
      received IMRT or 3DCRT, reported a clinically meaningful decrement in the urinary
      irritation/obstruction domain. At 24 months, none of the 3 cohorts reported
      clinically meaningful changes in urinary QOL. CONCLUSIONS: Patients who received
      3DCRT, IMRT, or PBT reported distinct patterns of treatment-related QOL. Although
      the timing of toxicity varied between the cohorts, patients reported similar
      modest QOL decrements in the bowel domain and minimal QOL decrements in the
      urinary domains at 24 months. Prospective randomized trials are needed to further
      examine these differences.

PMID- 24679464
TI  - Commentary on "Toxicity after external beam radiotherapy for prostate cancer: an
      analysis of late morbidity in men with diabetes mellitus." Kalakota K, Liauw SL,
      Department of Radiation Oncology, Northwestern Memorial Hospital, Chicago, IL.:
      Urology 2013;81(6):1196-201. doi: 10.1016/j.urology.2013.01.047. [Epub 2013 Mar
      26].
AB  - OBJECTIVE: To investigate the influence of diabetes mellitus (DM) on late
      genitourinary (GU) and gastrointestinal (GI) toxicity in patients treated with
      external beam radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: A
      total of 626 men were treated with curative-intent RT for prostate cancer from
      1988 to 2008. Using the National Comprehensive Cancer Network risk category, the
      patients were considered to have low-risk (30%), intermediate-risk (42%), or high
      risk (28%) prostate cancer. The median radiation dose was 74 Gy; 45% received
      androgen deprivation therapy for a median of 4 months. Late GU and GI Radiation
      Therapy Oncology Group toxicity was recorded prospectively at each visit after
      external beam RT. The median follow-up period was 55 months. RESULTS: Of the 626
      men, 102 (16%) had DM that was controlled by diet (8%), oral medications (52%),
      or insulin (39%). The patients with DM were more likely to receive intensity
      modulated RT and androgen deprivation therapy and to have a shorter follow-up
      duration (P <=.05 for all). Univariate analyses demonstrated that greater
      radiation dose, baseline urinary dysfunction, intensity-modulated RT, and DM were
      associated with grade 2 or greater GU toxicity, and transurethral resection of
      the prostate and DM were associated with grade 3 or greater GU toxicity. In
      addition, androgen deprivation therapy use, age >= 70 years, and anticoagulation
      were associated with grade 2 or greater GI toxicity, and age >= 70 years and
      anticoagulation were associated with grade 3 or greater GI toxicity. The
      multivariate analyses for late toxicity demonstrated a greater risk of grade 2 or
      greater (relative risk 1.36, P = .10) and grade 3 or greater GU toxicity
      (relative risk 2.74, P = .04) with DM. CONCLUSION: A greater incidence of late GU
      toxicity was seen in patients with DM treated for prostate cancer. This
      relationship might be useful when considering the treatment of patients with DM,
      especially those receiving dose-escalated RT or with a history of transurethral
      resection of the prostate.

PMID- 24679465
TI  - Commentary on "A systematic review of stereotactic radiotherapy ablation for
      primary renal cell carcinoma." Siva S, Pham D, Gill S, Corcoran NM, Foroudi F.
      Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre,
      Victoria, Australia.: BJU Int 2012;110(11 Pt B):E737-43. doi: 10.1111/j.1464
      410X.2012.11550.x. [Epub 2012 Oct 29].
AB  - What's known on the subject? and What does the study add? At present, little is
      known about the role of stereotactic ablative body radiotherapy in the treatment
      of primary renal cell carcinoma. The published evidence to date totals 126
      patients worldwide. The majority of evidence is retrospective in nature. The
      present study adds context to the current literature by providing an overall
      summary of the evidence. OBJECTIVE: To critically assess the use of stereotactic
      ablative body radiotherapy (SABR) for the treatment of primary renal cell
      carcinoma with particular focus on local control and toxicity outcomes. METHODS:
      A systematic search on PubMed was performed in January 2012 independently by two
      radiation oncologists using structured search terms. Secondary manual searches
      were performed on citations in relevant publications and abstracts in major
      radiotherapy journals. Outcomes, techniques, biological doses and scientific
      rigour of the studies were analysed. RESULTS: In total 10 publications (seven
      retrospective and three prospective) were identified. A wide range of techniques,
      doses and dose fractionation schedules were found. A total of 126 patients were
      treated with between one and six fractions of SABR. Median or mean follow-up
      ranged from 9 to 57.5 months. A weighted local control was reported of 93.91%
      (range 84%-100%). The weighted rate of severe grade 3 or higher adverse events
      was 3.8% (range 0%-19%). The weighted rate of grade 1-2 minor adverse events was
      21.4% (range 0%-93%). The most commonly employed fractionation schedule was 40Gy
      delivered over five fractions. CONCLUSIONS: Current literature suggests that SABR
      for primary renal cell carcinoma can be delivered with promising rates of local
      control and acceptable toxicity. However, there was insufficient evidence to
      recommend a consensus view for dose fractionation or technique. This indicates
      the need for further prospective studies assessing the role of this technique in
      medically inoperable patients.

PMID- 24679466
TI  - Implicit attitudes and self-concepts towards transgression and aggression:
      differences between male community and offender adolescents, and associations
      with psychopathic traits.
AB  - Research suggests that implicit attitudes play a key role in the occurrence of
      antisocial behaviours. This study assessed implicit attitudes and self-concepts
      related to aggression and transgression in community and offender adolescents,
      using a new set of Implicit Association Tests (IATs), and examined their
      association with of psychopathic traits. Thirty-six offenders and 66 community
      adolescents performed 4 IATs assessing 1) implicit attitudes about a) aggression
      and b) transgression as good, and 2) implicit self-concepts about a) aggression
      and b) transgression as self-descriptive. They filled in self-report
      questionnaires: the Youth Psychopathic Traits Inventory, the Child Behaviour
      Checklist, and explicit measures of their attitudes and self-concepts towards
      transgression and aggression. Results showed few differences between community
      and offender adolescents on implicit attitudes and self-concepts, and unexpected
      negative associations between some implicit attitudes and psychopathic traits,
      while the association was positive for the corresponding explicit attitudes.
      Possible explanations of these findings are discussed. 

PMID- 24679467
TI  - Innate lymphoid cells and asthma.
AB  - Asthma is a complex and heterogeneous disease with several phenotypes, including
      an allergic asthma phenotype characterized by TH2 cytokine production and
      associated with allergen sensitization and adaptive immunity. Asthma also
      includes nonallergic asthma phenotypes, such as asthma associated with exposure
      to air pollution, infection, or obesity, that require innate rather than adaptive
      immunity. These innate pathways that lead to asthma involve macrophages,
      neutrophils, natural killer T cells, and innate lymphoid cells, newly described
      cell types that produce a variety of cytokines, including IL-5 and IL-13. We
      review the recent data regarding innate lymphoid cells and their role in asthma. 

PMID- 24679469
TI  - Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response
      in patients with moderate-to-severe psoriasis.
AB  - BACKGROUND: IL-23 expression is increased in psoriatic lesions and might regulate
      TH17 T-cell counts in patients with psoriasis. OBJECTIVES: We sought to test a
      novel IL-23-specific therapeutic agent for the treatment of psoriasis. METHODS:
      In this randomized, double-blind, placebo-controlled study the safety,
      tolerability, and clinical response of guselkumab, an anti-IL-23-specific mAb,
      were evaluated in patients with moderate-to-severe plaque psoriasis. A total of
      24 patients were randomized to receive a single dose of placebo or 10, 30, 100,
      or 300 mg of guselkumab. Clinical response was assessed by using the Psoriasis
      Area and Severity Index (PASI). Additionally, histologic analysis and gene
      expression in skin biopsy specimens from guselkumab-treated patients were
      compared with those from placebo-treated patients. RESULTS: At week 12, 50% (10
      mg), 60% (30 and 100 mg), and 100% (300 mg) of guselkumab-treated patients,
      respectively, achieved a 75% improvement in PASI scores from baseline compared
      with 0% of placebo-treated patients. Improvements in PASI scores were generally
      maintained through week 24 in all guselkumab-treated patients. The proportion of
      patients experiencing an adverse event was comparable between the combined
      guselkumab (13/20 [65.0%]) and placebo (2/4 [50.0%]) groups through week 24.
      Analysis of lesional and nonlesional skin biopsy specimens demonstrated decreases
      in epidermal thickness and T-cell and dendritic cell expression in guselkumab
      treated patients compared with values seen in placebo-treated patients. At week
      12, significant reductions in psoriasis gene expression and serum IL-17A levels
      were observed in guselkumab-treated patients. CONCLUSION: IL-23 inhibition with a
      single dose of guselkumab results in clinical responses in patients with moderate
      to-severe psoriasis, suggesting that neutralization of IL-23 alone is a promising
      therapy for psoriasis.

PMID- 24679471
TI  - Group 2 innate lymphoid cells facilitate sensitization to local, but not
      systemic, TH2-inducing allergen exposures.
AB  - BACKGROUND: Allergic inflammation involves the sensitization of naive CD4(+) T
      cells to allergens, resulting in a TH2-skewed inflammatory response. Although
      antigen presentation by dendritic cells to T cells in the lymph node is crucial
      for TH2 cell development, the innate signals that initiate adaptive type 2
      inflammation and the role of group 2 innate lymphoid cells (ILC2s) are poorly
      understood. OBJECTIVE: We sought to investigate the influence of ILC2s and the
      route of priming on the development of an adaptive type 2 immune response to lung
      allergens. METHODS: Wild-type and ILC2-deficient mice were exposed intranasally
      or systemically to the TH2-inducing antigens house dust mite or ovalbumin in a
      model of allergic airway inflammation or the TH17-inducing bacterial antigen
      Saccharopolyspora rectivirgula in a model of hypersensitivity pneumonitis. The
      formation of an adaptive immune response was evaluated based on serum antibody
      titers and production of T cell-derived cytokines (IL-4, IL-5, IL-13 and IL-17A).
      RESULTS: We find that lung ILC2s play a critical role in priming the adaptive
      type 2 immune response to inhaled allergens, including the recruitment of
      eosinophils, TH2 cytokine production and serum IgE levels. Surprisingly, systemic
      priming with ovalbumin, with or without adjuvants, circumvents the requirement
      for ILC2s in inducing TH2-driven lung inflammation. ILC2s were also found to be
      dispensable for the sensitization to TH1- or TH17-inducing antigens. CONCLUSION:
      These data highlight a critical role for ILC2s in the development of adaptive
      type 2 responses to local, but not systemic, antigen exposure.

PMID- 24679470
TI  - BCG vaccination in patients with severe combined immunodeficiency: complications,
      risks, and vaccination policies.
AB  - BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized
      by profound T-cell deficiency. BCG vaccine is contraindicated in patients with
      SCID. Because most countries encourage BCG vaccination at birth, a high
      percentage of patients with SCID are vaccinated before their immune defect is
      detected. OBJECTIVES: We sought to describe the complications and risks
      associated with BCG vaccination in patients with SCID. METHODS: An extensive
      standardized questionnaire evaluating complications, therapeutics, and outcomes
      regarding BCG vaccination in patients given a diagnosis of SCID was widely
      distributed. Summary statistics and association analysis was performed. RESULTS:
      Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries
      were analyzed. Fifty-one percent of the patients had BCG-associated
      complications, 34% disseminated and 17% localized (a 33,000- and 400-fold
      increase, respectively, over the general population). Patients receiving early
      vaccination (<=1 month) showed an increased prevalence of complications (P =
      .006) and death caused by BCG-associated complications (P < .0001). The odds of
      experiencing complications among patients with T-cell numbers of 250/MUL or less
      at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than
      among those with T-cell numbers of greater than 250/MUL. BCG-associated
      complications were reported in 2 of 78 patients who received antimycobacterial
      therapy while asymptomatic, and no deaths caused by BCG-associated complications
      occurred in this group. In contrast, 46 BCG-associated deaths were reported among
      160 patients treated with antimycobacterial therapy for a symptomatic BCG
      infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of
      complications in patients with SCID, which increase morbidity and mortality
      rates. Until safer and more efficient antituberculosis vaccines become available,
      delay in BCG vaccination should be considered to protect highly vulnerable
      populations from preventable complications.

PMID- 24679473
TI  - Reply: To PMID 23591271.

PMID- 24679472
TI  - Eosinophil count and efficacy of omalizumab treatment.

PMID- 24679474
TI  - Influenza vaccination in asthmatic patients.

PMID- 24679475
TI  - Effect of price capitation on implant selection for primary total hip and knee
      arthroplasty.
AB  - While price capitation strategies may help to control total hip (THA) and knee
      arthroplasty (TKA) implant costs, its effect on premium implant selection is
      unclear. Primary THA and TKA cases 6 months before and after capitated pricing
      implementation were retrospectively identified. After exclusions, 716 THA and 981
      TKA from a large academic hospital and 2 midsize private practice community
      hospitals were reviewed. Academic hospital surgeons increased premium THA implant
      usage (66.5% to 70.6%; P = 0.28), while community surgeons selected fewer premium
      implants (36.4%) compared to academic surgeons, with no practice change (P =
      0.95). Conversely, premium TKA implant usage significantly increased (73.4% to
      89.4%; P < 0.001) for academic surgeons. Community surgeons used premium TKA
      implants at greater rates in both periods, with all cases having >=1 premium
      criterion.

PMID- 24679476
TI  - Comparing parasitological vs serological determination of Schistosoma haematobium
      infection prevalence in preschool and primary school-aged children: implications
      for control programmes.
AB  - To combat schistosomiasis, the World Health Organization (WHO) recommends that
      infection levels are determined prior to designing and implementing control
      programmes, as the treatment regimens depend on the population infection
      prevalence. However, the sensitivity of the parasitological infection diagnostic
      method is less reliable when infection levels are low. The aim of this study was
      to compare levels of Schistosoma haematobium infection obtained by the
      parasitological method vs serological technique. Infection levels in preschool
      and primary school-aged children and their implications for control programmes
      were also investigated. Infection prevalence based on serology was significantly
      higher compared with that based on parasitology for both age groups. The
      difference between infection levels obtained using the two methods increased with
      age. Consequentially, in line with the WHO guidelines, the serological method
      suggested a more frequent treatment regimen for this population compared with
      that implied by the parasitological method. These findings highlighted the
      presence of infection in children aged ?5 years, further reiterating the need for
      their inclusion in control programmes. Furthermore, this study demonstrated the
      importance of using sensitive diagnostic methods as this has implications on the
      required intervention controls for the population.

PMID- 24679477
TI  - Obstetrician-gynecologists and contraception: practice and opinions about the use
      of IUDs in nulliparous women, adolescents and other patient populations.
AB  - OBJECTIVES: Use of intrauterine devices (IUDs) by US women is low despite their
      suitability for most women of reproductive age and in a variety of clinical
      contexts. This study examined obstetrician-gynecologists' practices and opinions
      about the use of IUDs in adolescents, nulliparous women and other patient groups,
      as well as for emergency contraception. DESIGN: A survey questionnaire was sent
      to a computer-generated sample of 3000 fellows who were reflective of the
      American College of Obstetricians and Gynecologists (College) membership.
      RESULTS: After exclusions from the 1552 returned surveys (51.7% response rate),
      1150 eligible questionnaires were analyzed. Almost all obstetrician-gynecologists
      (95.8%) reported providing IUDs, but only 66.8% considered nulliparous women, and
      43.0% considered adolescents appropriate candidates. Even among obstetrician
      gynecologists who recalled reading a College publication about IUDs, only 78.0%
      and 45.0% considered nulliparous women and adolescents appropriate candidates,
      respectively. Few respondents (16.1%) had recommended the copper IUD as emergency
      contraception, and only 73.9% agreed that the copper IUD could be used as
      emergency contraception. A total of 67.3% of respondents agreed that an IUD can
      be inserted immediately after an abortion or miscarriage. Fewer (43.5%) agreed
      that an IUD can be inserted immediately postpartum, and very few provide these
      services (11.4% and 7.2%, respectively). Staying informed about practice
      recommendations for long-acting reversible contraception was associated with
      broader provision of IUDs. CONCLUSIONS: Although most obstetrician-gynecologists
      offer IUDs, many exclude appropriate candidates for IUD use, both for emergency
      contraception and for long-term use, despite evidence-based recommendations.
      IMPLICATIONS: This study shows that obstetrician-gynecologists still do not offer
      IUDs to appropriate candidates, such as nulliparous women and adolescents, and
      rarely provide the copper IUD as emergency contraception.

PMID- 24679478
TI  - Extended use of the intrauterine device: a literature review and recommendations
      for clinical practice.
AB  - There are multiple advantages to "extended use" of the intrauterine device (IUD)
      use beyond the manufacturer-approved time period, including prolongation of
      contraceptive and non-contraceptive benefits. We performed a literature review of
      studies that have reported pregnancy outcomes associated with extended use of
      IUDs, including copper IUDs and the levonorgestrel intrauterine system (LNG-IUS).
      Among parous women who are at least 25 years old at the time of IUD insertion,
      there is good evidence to support extended use of the following devices: the
      TCu380A and the TCu220 for 12 years, the Multiload Cu-375 for 10 years, the
      frameless GyneFix(r) (330 mm2) for 9 years, the levonorgestrel intrauterine
      system 52 mg (Mirena(r)) for 7 years and the Multiload Cu-250 for 4 years. Women
      who are at least 35 years old at the time of insertion of a TCu380A IUD can
      continue use until menopause with a negligible risk of pregnancy. We found no
      data to support use of the LNG-IUS 13.5 mg (Skyla(r)) beyond 3 years. When
      counseling about extended IUD use, clinicians should consider patient
      characteristics and preferences, as well as country- and community-specific
      factors. Future research is necessary to determine the risk of pregnancy
      associated with extended use of the copper IUD and the LNG-IUS among nulliparous
      women and women less than 25 years old at the time of IUD insertion. More data
      are needed on the potential effect of overweight and obesity on the long-term
      efficacy of the LNG-IUS.

PMID- 24679479
TI  - Medical students' attitudes and perceptions on abortion: a cross-sectional survey
      among medical interns in Maharastra, India.
AB  - INTRODUCTION: Although abortion care has been an established routine since
      decades in India, 8% of maternal mortality is attributed to unsafe abortion.
      Increased knowledge and improved attitudes among health care providers have a
      potential to reduce barriers to safe abortion care by reducing stigma and
      reluctance to provide abortion. Previous research has shown that medical
      students' attitudes can predict whether they will perform abortions. The
      objective of our study was to explore attitudes toward abortion among medical
      interns in Maharastra, India. STUDY DESIGN: A cross-sectional survey was carried
      out among 1996 medical interns in Maharastra, India. Descriptive and analytical
      statistics were used to interpret the study instrument. RESULTS: Almost one
      quarter of the respondents considered abortion to be morally wrong, one fifth did
      not find abortions for unmarried women acceptable and one quarter falsely
      believed that a woman needs her partner or spouse's approval to have an abortion.
      Most participants agreed that unsafe abortion is a serious health problem in
      India. A majority of the respondents rated their knowledge of sexual and
      reproductive health as good, but only 13% had any clinical practice in abortion
      care services. CONCLUSION: Disallowing attitudes toward abortion and
      misconceptions about the legal regulations were common among the surveyed medical
      students. Knowledge and attitudes toward abortion among future physicians could
      be improved by amendments to the medical education, potentially increasing the
      number of future providers delivering safe and legal abortion services.
      IMPLICATION PARAGRAPH: Abortion is legal in India since decades, but maternal
      mortality due to unsafe abortions remains high. This survey of attitudes toward
      abortion among medical interns in Maharastra indicates that disallowing views
      prevail. Improved knowledge and clinical training can increase numbers of
      potential abortion providers, thus limit unsafe abortion.

PMID- 24679480
TI  - Effect of pregnancy on endometrial expression of luteolytic pathway components in
      the mare.
AB  - Endometrial oxytocin receptors (OXTR) and prostaglandin-endoperoxide synthase 2
      (PTGS2) are central components of the luteolytic pathway in cyclic mares, and
      their suppression is thought to be critical to luteal maintenance during early
      pregnancy. We examined the effect of pregnancy on endometrial expression of
      potential regulators of prostaglandin (PG) F2alpha secretion in mares. Expression
      of the nuclear progesterone receptor and oestrogen receptor ERalpha was high
      during oestrus, and depressed when progesterone was elevated; the opposite
      applied to the membrane progesterone receptor. PTGS2 was upregulated on Day 14 of
      dioestrus, but not pregnancy. Although OXTR mRNA expression was not elevated on
      Day 14 of dioestrus, protein abundance was; this increase in OXTR protein was
      absent on Day 14 of pregnancy. Intriguingly, gene and protein expression for
      PTGS2 and OXTR increased markedly between Days 14 and 21 of pregnancy suggesting
      that, although initial avoidance of luteolysis during pregnancy involves their
      suppression, this is a transient measure that delays rather than abolishes
      luteolytic pathway generation. The only oxytocin-PGF2alpha feedback loop
      component downregulated on both Days 14 and 21 of pregnancy was the PGF2alpha
      receptor we propose that downregulation of the PGF2alpha receptor uncouples the
      oxytocin-PGF2alpha feedback loop, thereby preventing generation of the large
      PGF2alpha pulses required for luteolysis. 

PMID- 24679481
TI  - [KCNH2 gene new mutation in a patient with prior diagnosis of epilepsy].

PMID- 24679482
TI  - [Musical hallucinations as a presenting manifestation of a left temporo-insular
      glioma].

PMID- 24679484
TI  - Intracranial neurenteric cyst mimicking prepontine subarachnoid hemorrhage.

PMID- 24679483
TI  - [Remote cerebellar hemorrhage following spinal surgery].

PMID- 24679485
TI  - Use of ponazuril paste to treat coccidiosis in shelter-housed cats and dogs.
AB  - Cystoisospora (synonym Isospora) spp. infections are common in dogs and cats
      worldwide, especially in crowded or unsanitary environments. Ponazuril
      (toltrazuril sulfone) is a widely used oral treatment, but protocols that will
      produce oocyst excretion below the detection limit in shelter-housed animals have
      not been determined. The aim of this study was to determine the efficacy of
      ponazuril paste at each of three dosages (dosage 1, 50mg/kg q24 h for 3 days,
      dogs n=14, cats n=16; dosage 2, 50mg/kg as a single dose, dogs n=13, cats n=25;
      or dosage 3, 20mg/kg as a single dose, dogs n=16, cats n=23) in shelter-housed
      dogs (n=43) and cats (n=64) with confirmed coccidiosis. Fecal oocyst counts and
      identification and fecal consistency scoring was performed pre-treatment (Day 1)
      and again at Day 3-4 and Day 8. There were higher proportions of animals with
      oocyst excretion below the detection limit at both Day 3-4 and Day 8 in the
      dosage 1 group (dogs 92.9%, cats 87.5%) than in the other two groups (dosage 2,
      dogs 76.9%, cats 80.0%; dosage 3, dogs 68.8%, cats 47.8%). Animals with high
      fecal oocyst counts at Day 1 were significantly more likely to be infected at Day
      3-4 (dogs, P<0.001; cats, P=0.013). Fecal consistency score at Day 3-4 was not
      significantly related to infection status (dogs, P=0.898; cats, P=0.136). Further
      studies are warranted to investigate a ponazuril protocol that can safely reduce
      fecal oocyst burdens in infected dogs and cats to levels below the detection
      limit. Environmental decontamination is also important to reduce the likelihood
      of re-infection.

PMID- 24679486
TI  - Chromosomal anomalies in primary cutaneous follicle center cell lymphoma do not
      portend a poor prognosis.
AB  - BACKGROUND: The t(14;18)(q32;q21) chromosomal translocation is found in the
      majority of nodal follicular lymphomas but only rarely in primary cutaneous
      follicle center cell lymphomas (PCFCL). Recent studies have postulated that the
      translocation is more prevalent in PCFCL than previously described and that it
      might be a molecular prognostic marker. OBJECTIVES: The purpose of our study was
      to analyze cases of PCFCL for the presence of a t(14;18) translocation using
      fluorescence in situ hybridization to detect balanced translocations involving
      either the BCL2 or MALT1 loci and to correlate the results with growth pattern,
      immunophenotype, and clinical outcome. METHOD: In all, 57 patients with PCFCL
      were extracted from our cutaneous lymphoma database. Retrospective analysis of
      clinical parameters including lesion type, location, diagnostic stage, lactate
      dehydrogenase, initial treatment, relapse rate, and survival was performed.
      RESULTS: In all, 57 patients with PCFCL were included in this study. We detected
      1 BCL2 chromosomal amplification, 4 translocations of BCL2, and 1 IGH/MALT1
      translocation. LIMITATIONS: This was a case series retrospective study.
      CONCLUSIONS: PCFCL has an excellent 5-year overall survival (100% disease
      specific survival). Chromosomal abnormalities of either BCL2 or MALT1 were
      detected in 10% of cases but do not correlate with a specific immune pathology or
      clinical outcome.

PMID- 24679487
TI  - Living with addiction: the perspectives of drug using and non-using individuals
      about sharing space in a hospital setting.
AB  - Hospitals seem to be places where harm reduction approaches could have great
      benefit but few have responded to the needs of people who use drugs. Drawing on
      recent theoretical contributions to harm reduction from health geography, we
      examine how the implementation of harm reduction is shaped by space and contested
      understandings of place and health. We examine how drug use and harm reduction
      approaches pose challenges and offer opportunities in hospital-based care using
      interview data from people living with HIV and who were or had recently been
      admitted to a hospital with an innovative harm reduction policy. Our data reveal
      the contested spatial arrangements (and the related practices and corporeal
      relations) that occur due to the discordance between harm reduction and hospital
      regulatory policy. Rather than de-stigmatising drug use at Casey House Hospital,
      the adoption of the harm reduction policy sparked inter-client conflict,
      reproduced dominant discourses about health and drug users, and highlights the
      challenges of sharing space when drug use is involved. The hospital setting
      produces particular ways of being for people who use and those who do not use
      drugs and the demarcation of space in a drug using context. Moving forward, harm
      reduction practice and research needs to consider more than just interactions
      between drug users and healthcare providers, or the role of administrative
      policies; it needs to position ethics at the forefront of understanding the
      collisions between people, drug use, place, and space. We raise questions about
      the relationship between subjectivity and spatial arrangements in mediating the
      success of harm reduction. 

PMID- 24679488
TI  - [Women-and Child-Friendly Institutional Strategies with an integral approach in
      Colombia].
AB  - It is uncommon to implement and document a maternal and child healthcare strategy
      on a territorial and institutional level is infrequent. Therefore, we aimed to
      describe the experience of a consulting team composed of two physicians, two
      nurses and two nutritionists, whose purpose was to support the introduction of
      the Women- and Child-Friendly Institutional Strategy with an integral approach in
      25 healthcare institutions in three Colombian departments (Cauca, Huila and
      Narino), according to unmet basic needs. The Women- and Child-Friendly
      Institutional Strategy, considered a senior management strategy, promotes a
      specific method that allows monitoring of institutions during the implementation
      of a health and nutritional care strategy for women and children, and offers them
      the possibility of voluntarily becoming accredited as a Women- and Child-Friendly
      Institutions.

PMID- 24679489
TI  - Does the achievement of an intermediate glycemic target reduce organ failure and
      mortality? A post hoc analysis of the Glucontrol trial.
AB  - OBJECTIVE: This research evaluates the impact of the achievement of an
      intermediate target glycemic band on the severity of organ failure and mortality.
      METHODS: Daily Sequential Organ Failure Assessment (SOFA) score and the
      cumulative time in a 4.0 to 7.0 mmol/L band (cTIB) were evaluated daily up to 14
      days in 704 participants of the multicentre Glucontrol trial (16 centers) that
      randomized patients to intensive group A (blood glucose [BG] target: 4.4-6.1
      mmol/L) or conventional group B (BG target: 7.8-10.0 mmol/L). Sequential Organ
      Failure Assessment evolution was measured by percentage of patients with SOFA
      less than or equal to 5 on each day, percentage of individual organ failures, and
      percentage of organ failure-free days. Conditional and joint probability analysis
      of SOFA and cTIB 0.5 or more assessed the impact of achieving 4.0 to 7.0 mmol/L
      target glycemic range on organ failure. Odds ratios (OR) compare the odds risk of
      death for cTIB 0.5 or more vs cTIB less than 0.5, where a ratio greater than 1.0
      indicates an improvement for achieving cTIB 0.5 or more independent of SOFA or
      glycemic target. RESULTS: Groups A and B were matched for demographic and
      severity of illness data. Blood glucose differed between groups A and B (P<.05),
      as expected. There was no difference in the percentage of patients with SOFA less
      than or equal to 5, individual organ failures, and organ failure-free days
      between groups A and B over days 1 to 14. However, 20% to 30% of group A patients
      failed to achieve cTIB 0.5 or more for all days, and significant crossover
      confounds interpretation. Mortality OR was greater than 1.0 for patients with
      cTIB 0.5 or more in both groups but much higher for group A on all days.
      CONCLUSIONS: There was no difference in organ failure in the Glucontrol study
      based on intention to treat to different glycemic targets. Actual outcomes and
      significant crossover indicate that this result may not be due to the difference
      in target or treatment. Odds ratios-associated achieving an intermediate 4.0 to
      7.0 mmol/L range improved outcome.

PMID- 24679490
TI  - Linburg-Comstock anomaly.

PMID- 24679491
TI  - Salvage of distal radius nonunion with a dorsal spanning distraction plate.
AB  - Treatment of nonunion after previous instrumentation of distal radius fractures
      represents a reconstructive challenge. Resultant osteopenia provides a poor
      substrate for fixation, often necessitating wrist fusion for salvage. A spanning
      dorsal distraction plate (bridge plate) can be a useful adjunct to neutralize
      forces across the wrist, alone or in combination with nonspanning plates to
      achieve union, salvage wrist function, and avoid wrist arthrodesis in distal
      radius nonunion. 

PMID- 24679492
TI  - Merkel cell carcinoma of the hand.

PMID- 24679493
TI  - Small intestine submucosa and mesenchymal stem cells composite gel for scarless
      vocal fold regeneration.
AB  - The purpose of this study is to demonstrate scarless vocal fold (VF) regeneration
      by using a composite gel composed of small intestine submucosa (SIS) and
      mesenchymal stem cells (MSCs). A scar was made with an electrocoagulator on both
      VFs in 24 rabbits, followed by injection of either MSCs, SIS, or MSCs-SIS
      composite gel in the right side VF, while the left side VF was left untreated. VF
      scars were evaluated with in vivo fluorescence live imaging system (IFLIS),
      endoscopy, histology, and videokymography (VKG) after eight weeks. IFLIS
      demonstrated that SIS enabled the MSCs to survive and be engrafted in the VF. The
      histological analysis showed increased hyaluronic acid accumulation and
      controlled collagen deposition by MSCs-SIS composite gel. VKG analysis showed
      more favorable vibrations of MSCs-SIS injected VF, compared to other treatment
      group. In conclusion, the injectable SIS supplied a niche for the MSCs to stably
      settle down in scarred VFs and helped to regulate ECM synthesis. The ECM
      remodeling underwent by the surviving MSCs eventually led to the functional
      improvement of the VF. The results of the present investigation suggest that SIS
      MSCs composite gel is a plausible biomaterial for prolonged survival of MSCs in
      VFs and promotes scarless VF healing.

PMID- 24679495
TI  - Invasive and noninvasive methods to diagnose portal hypertension and esophageal
      varices.
AB  - Assessing the presence of clinically significant portal hypertension and
      esophageal varices is clinically important in cirrhosis. The reference standard
      techniques to assess the presence of portal hypertension and varices are the
      measurement of the hepatic vein pressure gradient and esophagogastroduodenoscopy,
      respectively. Some newer methods have shown a good performance, but none has been
      proven precise enough to replace hepatic vein pressure gradient measurement or
      esophagogastroduodenoscopy for the diagnosis of portal hypertension or the
      presence and grade of esophageal varices. 

PMID- 24679496
TI  - Pharmacologic management of portal hypertension.
AB  - Progress in the knowledge of the pathophysiology of portal hypertension has
      disclosed new targets for therapy, resulting in a larger spectrum of drugs with a
      potential role for clinical practice. This review focuses on pharmacologic
      treatments already available for reducing portal pressure and summarizes drugs
      currently under investigation in this field. 

PMID- 24679494
TI  - Pathophysiology of portal hypertension.
AB  - Portal hypertension is a major complication of liver disease that results from a
      variety of pathologic conditions that increase the resistance to the portal blood
      flow into the liver. As portal hypertension develops, the formation of collateral
      vessels and arterial vasodilation progresses, which results in increased blood
      flow to the portal circulation. Hyperdynamic circulatory syndrome develops,
      leading to esophageal varices or ascites. This article summarizes the factors
      that increase (1) intrahepatic vascular resistance and (2) the blood flow in the
      splanchnic and systemic circulations in liver cirrhosis. In addition, the future
      directions of basic/clinical research in portal hypertension are discussed. 

PMID- 24679497
TI  - Role of transjugular intrahepatic portosystemic shunt in the management of portal
      hypertension.
AB  - A transjugular intrahepatic portosystemic shunt (TIPS) is an expandable metal
      stent inserted via the jugular vein that creates a shunt from the portal vein to
      the systemic circulation via an artificial communication through the liver. It is
      used to treat complications of portal hypertension. In addition to rescue
      treatment in variceal bleeding, TIPS can play an important role in prevention of
      rebleeding. TIPS can improve symptoms if medical treatment of ascites or hepatic
      hydrothrorax has failed, but may not improve survival. Selected cases of Budd
      Chiari syndrome improve with TIPS. This article discusses the indications,
      evidence, and complications of TIPS. 

PMID- 24679498
TI  - Primary prophylaxis of variceal bleeding.
AB  - Primary prevention of variceal bleeding is an important and long-debated topic in
      the management of patients with cirrhosis and esophageal varices. Prophylaxis is
      recommended for high-risk patients with small esophageal varices (advanced liver
      disease and/or presence of red wale marks) and those with medium/large varices.
      Nonselective beta-blockers and endoscopic band ligation have been shown to be
      equally effective in primary prevention of variceal bleeding and are the only
      currently recommended therapies. Controversy still exists, however, regarding
      which one of these strategies is preferred. This article reviews the established
      recommendations and recent advances in the prevention of first esophageal
      variceal bleeding. 

PMID- 24679500
TI  - Secondary prophylaxis for esophageal variceal bleeding.
AB  - Combination therapy with beta-blockers and endoscopic band ligation (EBL) is the
      standard prophylaxis of esophageal variceal rebleeding in cirrhosis. Beta
      blockers are the backbone of combination therapy, since their benefit extend to
      other complications of portal hypertension. EBL carries the risk of post-banding
      ulcer bleeding, which explains why overall rebleeding is reduced when beta
      blockers are added to EBL, and not when EBL is added to beta-blockers. TIPS is
      the rescue treatment, but it could be considered as first choice in patients that
      first bleed while on beta-blockers, those with contraindications to beta-blockers
      or with refractory ascites, and those with fundal varices. 

PMID- 24679499
TI  - Management of acute variceal bleeding.
AB  - Acute variceal bleeding (AVB) is the most common cause of upper gastrointestinal
      hemorrhage in patients with cirrhosis. Advances in the management of AVB have
      resulted in decreased mortality. To minimize mortality, a multidisciplinary
      approach addressing airway safety, prompt judicious volume resuscitation,
      vasoactive and antimicrobial pharmacotherapy, and early endoscopy to obliterate
      varices is necessary. Placement of a transjugular intrahepatic portosystemic
      shunt (TIPS) has been used as rescue therapy for patients failing initial
      attempts at hemostasis. Patients who have a high likelihood of failing initial
      attempts at hemostasis may benefit from a more aggressive approach using TIPS
      earlier in their management. 

PMID- 24679501
TI  - Gastric and ectopic varices.
AB  - Although often considered together, gastric and ectopic varices represent
      complications of a heterogeneous group of underlying diseases. Commonly, these
      are known to arise in patients with cirrhosis secondary to portal hypertension;
      however, they also arise in patients with noncirrhotic portal hypertension, most
      often secondary to venous thrombosis of the portal venous system. One of the key
      initial assessments is to define the underlying condition leading to the
      formation of these portal-collateral pathways to guide management. In the
      authors' experience, these patients can be grouped into distinct although
      sometimes overlapping conditions, which can provide a helpful conceptual basis of
      management. 

PMID- 24679502
TI  - Portal hypertensive gastropathy and colopathy.
AB  - Portal hypertensive gastropathy (PHG) and colopathy (PHC) are considered
      complications of portal hypertension. Both entities are clinically relevant
      because they may cause insidious blood loss or even acute massive
      gastrointestinal hemorrhage. Endoscopic evaluation is necessary for the diagnosis
      of PHG and PHC. The existence of different endoscopic criteria for PHG and PHC
      makes consensus difficult and results in a broad range of reported prevalence.
      Therapy targeted at reduction of portal pressure and mucosal blood flow has been
      used to treat acute bleeding; nonselective beta-blockers are the most frequently
      used agents. Further studies are needed to clarify the natural history,
      pathogenesis, and treatment of PHG and PHC. 

PMID- 24679503
TI  - Hepatopulmonary syndrome.
AB  - The hepatopulmonary syndrome (HPS) is a pulmonary complication of cirrhosis
      and/or portal hypertension whereby patients develop hypoxemia as a result of
      alterations in pulmonary microvascular tone and architecture. HPS occurs in up to
      30% of patients with cirrhosis. Although the degree of hypoxemia does not
      reliably correlate with the severity of liver disease, patients with HPS have a
      higher mortality than do patients with cirrhosis without the disorder. There has
      been progress into defining the mechanisms that lead to hypoxemia in HPS, but to
      date there are no therapeutic options for HPS aside from liver transplantation. 

PMID- 24679504
TI  - Portopulmonary hypertension.
AB  - Portopulmonary hypertension (POPH) is the presence of pulmonary arterial
      hypertension in patients with portal hypertension. Among liver transplant (LT)
      candidates, reported incidence rates of POPH range from 4.5% to 8.5%. In patients
      with LT, intraoperative death and immediate post-LT mortality are feared clinical
      events when transplantation is attempted in the setting of untreated, moderate to
      severe POPH; therefore, POPH precludes LT unless the mean pulmonary artery
      pressure can be reduced to a safe level and right ventricular function optimized.
      Specific pulmonary artery vasodilator medications seem effective in reducing
      pulmonary artery pressures and improving right ventricular function and survival.

PMID- 24679505
TI  - Hepatic hydrothorax.
AB  - Hepatic hydrothorax (HH) is an uncommon complication in patients with end-stage
      liver disease. Only 5% to 10% of patients with end-stage liver disease develop
      HH, which may result in dyspnea, hypoxia, and infection, and portends a poor
      prognosis. The most likely explanation for development is passage of fluid from
      the peritoneal space to the pleural space due to small diaphragmatic defects.
      Initial management consists of diuretics with dietary sodium restriction and
      thoracentesis, and a transjugular intrahepatic portosystemic shunt may ultimately
      be required. Afflicted patients can develop morbid and fatal complications, pose
      management dilemmas, and should warrant evaluation for liver transplantation. 

PMID- 24679506
TI  - Non-cirrhotic portal hypertension.
AB  - Non-cirrhotic portal hypertension (NCPH) encompasses a wide range of disorders,
      primarily vascular in origin, presenting with portal hypertension (PHT), but with
      preserved liver synthetic functions and near normal hepatic venous pressure
      gradient (HVPG). Non-cirrhotic portal fibrosis/Idiopathic PHT (NCPF/IPH) and
      extrahepatic portal venous obstruction (EHPVO) are two prototype disorders in the
      category. Etiopathogenesis in both of them centers on infections and
      prothrombotic states. Presentation and management strategies focus on repeated
      well tolerated episodes of variceal bleed and moderate to massive splenomegaly
      and other features of PHT. While the long-term prognosis is generally good in
      NCPF, portal biliopathy and parenchymal extinction after prolonged PHT makes
      outcome somewhat less favorable in EHPVO. While hepatic schistosomiasis,
      congenital hepatic fibrosis and nodular regenerative hyperplasia have their
      distinctive features, they often present with NCPH. 

PMID- 24679507
TI  - Surgery in patients with portal hypertension: a preoperative checklist and
      strategies for attenuating risk.
AB  - Patients with liver disease and portal hypertension are at increased risk of
      complications from surgery. Recent advances have allowed better optimization of
      patients with cirrhosis before surgery and a reduction in postoperative
      complications. Despite this progress, the estimation of surgical risk in a
      patient with cirrhosis is challenging. The MELD score has shown promise in
      predicting postoperative mortality compared with the Child-Turcotte-Pugh score.
      This article addresses current concepts in the perioperative evaluation of
      patients with liver disease and portal tension, including a preoperative liver
      assessment (POLA) checklist that may be useful towards mitigating perioperative
      complications. 

PMID- 24679508
TI  - Portal hypertension.

PMID- 24679510
TI  - Improving accuracy of acoustic source localization in anisotropic plates.
AB  - The acoustic source localization technique for anisotropic plates proposed by the
      authors in an earlier publication ([1] Kundu et al., 2012) is improved in this
      paper by adopting some modifications. The improvements are experimentally
      verified on anisotropic flat and curved composite plates. Difficulties associated
      with the original technique were first investigated before making any
      modification. It was noted that the accuracy of this technique depends strongly
      on the accuracy of the measured time difference of arrivals (TDOA) at different
      receiving sensors placed in close proximity in a sensor cluster. The sensor
      cluster is needed to obtain the direction of the acoustic source without knowing
      the material properties of the plate. Two modifications are proposed to obtain
      the accurate TDOA. The first one is to replace the recorded full time histories
      by only their initial parts - the first dip and peak - for the subsequent signal
      processing. The second modification is to place the sensors in the sensor cluster
      as close as possible. It is shown that the predictions are improved significantly
      with these modifications. These modifications are then applied to another sensor
      cluster based technique called the beamforming technique, to see if similar
      improvements are achieved for that technique also with these modifications. 

PMID- 24679509
TI  - Effects of long-term supplementation of chestnut and valonea extracts on methane
      release, digestibility and nitrogen excretion in sheep.
AB  - The long-term effects of adding chestnut (CHE; Castanea sativa) and valonea (VAL;
      Quercus valonea) tannin-rich extracts to sheep feed were investigated. In
      Experiment 1, sheep (65 kg BW) were fed 842 g/day of a ryegrass-based hay. The
      control-treated animals (CON) received 464 g/day of concentrate, and tannin
      treated animals received the same amount of concentrate additionally containing
      20 g of the respective tannin-rich extract. Hay and concentrates were offered
      together in one meal. After the onset of treatment, methane release was measured
      in respiration chambers for 23.5-h intervals (nine times) in a 190-days period.
      Faeces and urine were collected three times (including once before the onset of
      the tannin treatment) to assess digestibility and urinary excretion of purine
      derivatives. Based on the results obtained from Experiment 1, a second experiment
      (Experiment 2) was initiated, in which the daily tannin dosage was almost doubled
      (from 0.9 (Experiment 1) to 1.7 g/kg BW0.75). With the exception of the dosage
      and duration of the treatment (85 days), Experiment 2 followed the same design as
      Experiment 1, with the same measurements. In an attempt to compare in vitro and
      in vivo effects of tannin supplementation, the same substrates and tannin
      treatments were examined in the Hohenheim gas test. In vitro methane production
      was not significantly different between treatments. None of the tannin-rich
      extract doses induced a reduction in methane in the sheep experiments. On the 1st
      day of tannin feeding in both experiments, tannin inclusion tended to decrease
      methane release, but this trend disappeared by day 14 in both experiments. In
      balance period 3 of Experiment 1, lower dry matter and organic matter
      digestibility was noted for tannin treatments. The digestibility of CP, but not
      NDF or ADF, was reduced in both experiments. A significant shift in N excretion
      from urine to faeces was observed for both tannin-rich extracts in both
      experiments, particularly in Experiment 2. In balance period 2 of Experiment 2,
      an increased intake of metabolisable energy for VAL was observed. The urinary
      excretion of purine derivatives was not significantly different between
      treatments, indicating that microbial protein synthesis was equal for all
      treatments. Thus, we concluded that both tannin-rich extracts temporary affect
      processes in the rumen but did not alter methane release over a longer period. 

PMID- 24679511
TI  - Ultrasonic sensor for predicting sugar concentration using multivariate
      calibration.
AB  - This paper presents a multivariate regression method for the prediction of
      maltose concentration in aqueous solutions. For this purpose, time and frequency
      domain of ultrasonic signals are analyzed. It is shown, that the prediction of
      concentration at different temperatures is possible by using several multivariate
      regression models for individual temperature points. Combining these models by a
      linear approximation of each coefficient over temperature results in a unified
      solution, which takes temperature effects into account. The benefit of the
      proposed method is the low processing time required for analyzing online signals
      as well as the non-invasive sensor setup which can be used in pipelines. Also the
      ultrasonic signal sections used in the presented investigation were extracted out
      of buffer reflections which remain primarily unaffected by bubble and particle
      interferences. Model calibration was performed in order to investigate the
      feasibility of online monitoring in fermentation processes. The temperature range
      investigated was from 10  degrees C to 21  degrees C. This range fits to
      fermentation processes used in the brewing industry. This paper describes the
      processing of ultrasonic signals for regression, the model evaluation as well as
      the input variable selection. The statistical approach used for creating the
      final prediction solution was partial least squares (PLS) regression validated by
      cross validation. The overall minimum root mean squared error achieved was 0.64
      g/100 g.

PMID- 24679512
TI  - A scanning acoustic microscope based on picosecond ultrasonics.
AB  - We report on the development of a new type of scanning acoustic microscope. We
      use a femtosecond light pulse to generate a short sound pulse, and then focus
      this sound onto the sample by means of a specially designed and microfabricated
      acoustic lens of radius a few microns. The sound travels to the sample through a
      thin layer of water. The sound reflected from the sample is collected by the lens
      and then passes through a monolithically integrated optical resonant cavity. The
      induced change in the properties of this cavity are measured using a time-delayed
      probe light pulse. We describe some of the challenges involved in the
      construction and operation of this high-precision metrology apparatus and present
      some preliminary results. 

PMID- 24679513
TI  - Plasma microRNAs as biomarkers for myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) lacks non-invasive and easy to measure
      biomarkers, still largely relying on semi-quantitative tests for diagnostic and
      prognostic purposes. Muscle biopsies provide valuable data, but their use is
      limited by their invasiveness. microRNA (miRNAs) are small non-coding RNAs
      regulating gene expression that are also present in biological fluids and may
      serve as diseases biomarkers. Thus, we tested plasma miRNAs in the blood of 36
      DM1 patients and 36 controls. First, a wide miRNA panel was profiled in a patient
      subset, followed by validation using all recruited subjects. We identified a
      signature of nine deregulated miRNAs in DM1 patients: eight miRNAs were increased
      (miR-133a, miR-193b, miR-191, miR-140-3p, miR-454, miR-574, miR-885-5p, miR-886
      3p) and one (miR-27b) was decreased. Next, the levels of these miRNAs were used
      to calculate a "DM1-miRNAs score". We found that both miR-133a levels and DM1
      miRNAs score discriminated DM1 from controls significantly and Receiver-Operator
      Characteristic curves displayed an area under the curve of 0.94 and 0.97,
      respectively. Interestingly, both miR-133a levels and DM1-miRNAs score displayed
      an inverse correlation with skeletal muscle strength and displayed higher values
      in more compromised patients. In conclusion, we identified a characteristic
      plasma miRNA signature of DM1. Although preliminary, this study indicates miRNAs
      as potential DM1 humoral biomarkers. 

PMID- 24679515
TI  - The impact of social support on psychological distress for U.S. Afghanistan/Iraq
      era veterans with PTSD and other psychiatric diagnoses.
AB  - This study aimed to examine the degree to which posttraumatic stress disorder
      (PTSD) affects the relationship between social support and psychological distress
      for U.S. Afghanistan/Iraq era veterans with and without co-occurring psychiatric
      disorders. Veterans (N=1825) were administered self-report questionnaires and a
      structured diagnostic interview as part of a multi-site study of post-deployment
      mental health through the Department of Veterans Affairs (VA) Mid-Atlantic Mental
      Illness Research, Education and Clinical Center (MIRECC). Main and interaction
      effects models assessed the association between psychological distress and social
      support for three comparisons conditions (Controls vs. PTSD-only, non-PTSD, and
      PTSD plus co-morbid diagnoses). Having PTSD was a critical factor in attenuating
      the strength of this association, more so than other diagnoses. Furthermore,
      those with PTSD plus co-morbid diagnoses did not demonstrate significantly larger
      attenuation in that association compared to the PTSD-only group, indicating that
      psychiatric comorbidity may be less important in considering the role of social
      support in PTSD. By understanding this relationship, new avenues for engaging and
      enhancing treatment outcomes related to social support for veterans of this
      cohort may be identified. Additional longitudinal research could help evaluate
      the effect of PTSD symptom clusters, social support type, and trauma exposure
      type on these relationships. 

PMID- 24679516
TI  - Psychosocial predictors of health outcomes in colorectal cancer: a comprehensive
      review.
AB  - BACKGROUND: A diagnosis of colorectal cancer (CRC) and its long-term treatment
      may lead to significant psychological distress and impaired health-related
      quality of life (HRQoL) for a significant proportion of patients. METHODS: We
      searched the PubMed/MEDLINE electronic database for available literature on the
      associations between personality characteristics, depression, psychological
      distress and HRQoL in CRC. Additional references were identified through the
      citation tracking of the included articles. RESULTS: Recent evidence indicates
      that Type-D (distressed) personality may predict distress among CRC patients.
      Additionally, other personality traits, such as specific ego defense mechanisms,
      influence the coping responses and HRQoL. Although the presence of a stoma has
      been linked to the development of depressive symptoms and impairment in HRQoL in
      CRC patients, more prospective studies are necessary to confirm these
      associations. Sense of coherence (SOC) has both a moderating and mediating effect
      on health (especially mental health and HRQoL), and preliminary data indicate
      that SOC may be an independent predictor of CRC survival. CONCLUSIONS: The
      interplay between personality variables during the elaboration of "the impaired
      role" is complex, and the assessment of personality traits may be incorporated
      into a comprehensive psychosomatic evaluation of CRC patients. More well-designed
      prospective investigations are necessary to establish the contributory role of
      personality dimensions for the development of and protection from distress and
      impairment in the HRQoL of CRC patients, which could eventually lead to the
      development of psychosocial interventions that are personalized to this patient
      population (for example, manual-based psychotherapies).

PMID- 24679514
TI  - Heterogeneous depression responses to chronic pain onset among middle-aged
      adults: a prospective study.
AB  - Studies on depression response to chronic pain are limited by lack of
      clarification of different forms of response patterns and cross-sectional
      measures. The current study examined heterogeneous long-term patterns of
      depression response to chronic pain onset prospectively using the mixture
      modeling technique. Depression symptoms prior to and following pain onset over a
      course of six years were charted in a nationally representative middle-aged
      sample. Four distinct depression symptom trajectories emerged. The resilience
      (72.0%) trajectory describes a pattern of no/minimal depression symptoms prior to
      and following pain onset. The post-pain depression trajectory (11.4%) describes a
      pattern of low depression at baseline and increasing symptoms following pain
      onset. The chronic depression (6.8%) trajectory is characterized by persistently
      high depression symptoms irrespective of pain onset. The prior depression
      improved (9.8%) trajectory describes a pattern of high depression at baseline and
      gradually declining symptoms following pain onset. Self-rated health at both
      baseline and following pain onset predicted the resilience trajectory. Baseline
      self-rated health distinguished the post-pain depression and chronic depression
      trajectories. Individuals in the prior depression improved trajectory were older
      and had more chronic illnesses at baseline but fewer illnesses following pain
      onset, compared to those in the resilience or post-pain depression trajectory. 

PMID- 24679517
TI  - Cryptosporidium infections: molecular advances.
AB  - Cryptosporidium host cell interaction remains fairly obscure compared with other
      apicomplexans such as Plasmodium or Toxoplasma. The reason for this is probably
      the inability of this parasite to complete its life cycle in vitro and the lack
      of a system to genetically modify Cryptosporidium. However, there is a
      substantial set of data about the molecules involved in attachment and invasion
      and about the host cell pathways involved in actin arrangement that are altered
      by the parasite. Here we summarize the recent advances in research on host cell
      infection regarding the excystation process, attachment and invasion, survival in
      the cell, egress and the available data on omics.

PMID- 24679518
TI  - Absence of in vivo-in vitro correlation in per-oral drug delivery.

PMID- 24679519
TI  - Students' and experts' perspectives on three learning and teaching activities.
AB  - Nursing is a profession that closely related to human life, and nurses are
      required to demonstrate critical thinking and creativity in providing health care
      services. However, traditional teaching approaches usually limit students'
      autonomy and freedom of expressing their thoughts and feelings. In order to
      develop the corresponding competence of nursing students, I adopted three
      teaching innovations, namely writing poems, composing songs, and using role plays
      in a nursing problem-based learning class in a university in Hong Kong. According
      to students' reflective notes and comments from two international expert
      reviewers, participating in these activities is a valuable experience and
      students were able to develop clinical reasoning, empathy, team spirit,
      motivation to learn, creativity, and ability to summarise and reconstruct
      knowledge. It is hoped that more innovative learning activities will be
      implemented, to prepare professional and ethical nurses in the future. It is also
      hoped that this study could provide other PBL educators some insights in
      innovative problem-based learning activities. 

PMID- 24679520
TI  - Pulling it all together.

PMID- 24679521
TI  - Discovering the power of single molecules.
AB  - Mechanical manipulations of single biological molecules have revealed highly
      dynamic and mechanical processes at the molecular level. Recent developments have
      permitted examination of the impact of torque on these processes and
      visualization of detailed molecular motions, enabling studies of increasingly
      complex systems. Here we highlight some recent important discoveries. 

PMID- 24679522
TI  - Every cell is special: genome-wide studies add a new dimension to single-cell
      biology.
AB  - Single-cell analyses have provided invaluable insights into studying
      heterogenity, signaling, and stochastic gene expression. Recent technological
      advances now open the door to genome-wide single-cell studies. 

PMID- 24679523
TI  - Looping back to leap forward: transcription enters a new era.
AB  - Comparative genome analyses reveal that organismal complexity scales not with
      gene number but with gene regulation. Recent efforts indicate that the human
      genome likely contains hundreds of thousands of enhancers, with a typical gene
      embedded in a milieu of tens of enhancers. Proliferation of cis-regulatory DNAs
      is accompanied by increased complexity and functional diversification of
      transcriptional machineries recognizing distal enhancers and core promoters and
      by the high-order spatial organization of genetic elements. We review progress in
      unraveling one of the outstanding mysteries of modern biology: the dynamic
      communication of remote enhancers with target promoters in the specification of
      cellular identity. 

PMID- 24679524
TI  - Remote control of gene function by local translation.
AB  - The subcellular position of a protein is a key determinant of its function.
      Mounting evidence indicates that RNA localization, where specific mRNAs are
      transported subcellularly and subsequently translated in response to localized
      signals, is an evolutionarily conserved mechanism to control protein
      localization. On-site synthesis confers novel signaling properties to a protein
      and helps to maintain local proteome homeostasis. Local translation plays
      particularly important roles in distal neuronal compartments, and dysregulated
      RNA localization and translation cause defects in neuronal wiring and survival.
      Here, we discuss key findings in this area and possible implications of this
      adaptable and swift mechanism for spatial control of gene function. 

PMID- 24679526
TI  - Differential scales of protein quality control.
AB  - Proteins are notorious for their unpleasant behavior-continually at risk of
      misfolding, collecting damage, aggregating, and causing toxicity and disease. To
      counter these challenges, cells have evolved elaborate chaperone and quality
      control networks that can resolve damage at the level of the protein, organelle,
      cell, or tissue. On the smallest scale, the integrity of individual proteins is
      monitored during their synthesis. On a larger scale, cells use compartmentalized
      defenses and networks of communication, capable sometimes of signaling between
      cells, to respond to changes in the proteome's health. Together, these layered
      defenses help protect cells from damaged proteins. 

PMID- 24679525
TI  - Nice neighborhood: emerging concepts of the stem cell niche.
AB  - No metazoan cell survives on its own, absent the signals and support of its
      milieu. For multicellular life with specialized tissues to persist, organization
      is everything and so defining the association of position with cell state is
      critical to understanding how tissues function, maintain, and repair. This review
      focuses specifically on place for progenitor and stem cells. Especially
      emphasized are hematopoietic cells that balance free movement and stable position
      and where concepts of regulatory interrelationships have been shown with some
      precision. It reviews classical and emerging concepts of the niche, particularly
      considering how niche functions may participate in neoplastic disease. 

PMID- 24679527
TI  - To be or not to be? How selective autophagy and cell death govern cell fate.
AB  - The health of metazoan organisms requires an effective response to organellar and
      cellular damage either by repair of such damage and/or by elimination of the
      damaged parts of the cells or the damaged cell in its entirety. Here, we consider
      the progress that has been made in the last few decades in determining the fates
      of damaged organelles and damaged cells through discrete, but genetically
      overlapping, pathways involving the selective autophagy and cell death machinery.
      We further discuss the ways in which the autophagy machinery may impact the
      clearance and consequences of dying cells for host physiology. Failure in the
      proper removal of damaged organelles and/or damaged cells by selective autophagy
      and cell death processes is likely to contribute to developmental abnormalities,
      cancer, aging, inflammation, and other diseases.

PMID- 24679528
TI  - The noncoding RNA revolution-trashing old rules to forge new ones.
AB  - Noncoding RNAs (ncRNAs) accomplish a remarkable variety of biological functions.
      They regulate gene expression at the levels of transcription, RNA processing, and
      translation. They protect genomes from foreign nucleic acids. They can guide DNA
      synthesis or genome rearrangement. For ribozymes and riboswitches, the RNA
      structure itself provides the biological function, but most ncRNAs operate as RNA
      protein complexes, including ribosomes, snRNPs, snoRNPs, telomerase, microRNAs,
      and long ncRNAs. Many, though not all, ncRNAs exploit the power of base pairing
      to selectively bind and act on other nucleic acids. Here, we describe the pathway
      of ncRNA research, where every established "rule" seems destined to be
      overturned. 

PMID- 24679529
TI  - Transgenerational epigenetic inheritance: myths and mechanisms.
AB  - Since the human genome was sequenced, the term "epigenetics" is increasingly
      being associated with the hope that we are more than just the sum of our genes.
      Might what we eat, the air we breathe, or even the emotions we feel influence not
      only our genes but those of descendants? The environment can certainly influence
      gene expression and can lead to disease, but transgenerational consequences are
      another matter. Although the inheritance of epigenetic characters can certainly
      occur-particularly in plants-how much is due to the environment and the extent to
      which it happens in humans remain unclear. 

PMID- 24679530
TI  - Rethinking differentiation: stem cells, regeneration, and plasticity.
AB  - Cell differentiation is an essential process for the development, growth,
      reproduction, and longevity of all multicellular organisms, and its regulation
      has been the focus of intense investigation for the past four decades. The study
      of natural and induced stem cells has ushered an age of re-examination of what it
      means to be a stem or a differentiated cell. Past and recent discoveries in
      plants and animals, as well as novel experimental manipulations, are beginning to
      erode many of these established concepts and are forcing a re-evaluation of the
      experimental systems and paradigms presently being used to explore these and
      other biological process. 

PMID- 24679532
TI  - The virome in mammalian physiology and disease.
AB  - The virome contains the most abundant and fastest mutating genetic elements on
      Earth. The mammalian virome is constituted of viruses that infect host cells,
      virus-derived elements in our chromosomes, and viruses that infect the broad
      array of other types of organisms that inhabit us. Virome interactions with the
      host cannot be encompassed by a monotheistic view of viruses as pathogens.
      Instead, the genetic and transcriptional identity of mammals is defined in part
      by our coevolved virome, a concept with profound implications for understanding
      health and disease. 

PMID- 24679533
TI  - Integrating biological redesign: where synthetic biology came from and where it
      needs to go.
AB  - Synthetic biology seeks to extend approaches from engineering and computation to
      redesign of biology, with goals such as generating new chemicals, improving human
      health, and addressing environmental issues. Early on, several guiding principles
      of synthetic biology were articulated, including design according to
      specification, separation of design from fabrication, use of standardized
      biological parts and organisms, and abstraction. We review the utility of these
      principles over the past decade in light of the field's accomplishments in
      building complex systems based on microbial transcription and metabolism and
      describe the progress in mammalian cell engineering. 

PMID- 24679534
TI  - The molecular and systems biology of memory.
AB  - Learning and memory are two of the most magical capabilities of our mind.
      Learning is the biological process of acquiring new knowledge about the world,
      and memory is the process of retaining and reconstructing that knowledge over
      time. Most of our knowledge of the world and most of our skills are not innate
      but learned. Thus, we are who we are in large part because of what we have
      learned and what we remember and forget. In this Review, we examine the
      molecular, cellular, and circuit mechanisms that underlie how memories are made,
      stored, retrieved, and lost. 

PMID- 24679531
TI  - Role of the microbiota in immunity and inflammation.
AB  - The microbiota plays a fundamental role on the induction, training, and function
      of the host immune system. In return, the immune system has largely evolved as a
      means to maintain the symbiotic relationship of the host with these highly
      diverse and evolving microbes. When operating optimally, this immune system
      microbiota alliance allows the induction of protective responses to pathogens and
      the maintenance of regulatory pathways involved in the maintenance of tolerance
      to innocuous antigens. However, in high-income countries, overuse of antibiotics,
      changes in diet, and elimination of constitutive partners, such as nematodes, may
      have selected for a microbiota that lack the resilience and diversity required to
      establish balanced immune responses. This phenomenon is proposed to account for
      some of the dramatic rise in autoimmune and inflammatory disorders in parts of
      the world where our symbiotic relationship with the microbiota has been the most
      affected. 

PMID- 24679535
TI  - A framework for studying emotions across species.
AB  - Since the 19th century, there has been disagreement over the fundamental question
      of whether "emotions" are cause or consequence of their associated behaviors.
      This question of causation is most directly addressable in genetically tractable
      model organisms, including invertebrates such as Drosophila. Yet there is ongoing
      debate about whether such species even have "emotions," as emotions are typically
      defined with reference to human behavior and neuroanatomy. Here, we argue that
      emotional behaviors are a class of behaviors that express internal emotion
      states. These emotion states exhibit certain general functional and adaptive
      properties that apply across any specific human emotions like fear or anger, as
      well as across phylogeny. These general properties, which can be thought of as
      "emotion primitives," can be modeled and studied in evolutionarily distant model
      organisms, allowing functional dissection of their mechanistic bases and tests of
      their causal relationships to behavior. More generally, our approach not only
      aims at better integration of such studies in model organisms with studies of
      emotion in humans, but also suggests a revision of how emotion should be
      operationalized within psychology and psychiatry. 

PMID- 24679537
TI  - The human condition-a molecular approach.
AB  - Research into when and where modern humans originated and how they differ from,
      and interacted with, other now-extinct forms of human has so far been the realm
      of archaeologists and paleoanthropologists. However, over the past decade,
      molecular geneticists have begun to study genomes of extinct humans. Here, I
      discuss where we stand today with respect to understanding how modern humans came
      to differ from Neandertals and other human forms that existed until about 30,000
      years ago. 

PMID- 24679536
TI  - Psychiatric disorders: diagnosis to therapy.
AB  - Recent findings in a range of scientific disciplines are challenging the
      conventional wisdom regarding the etiology, classification, and treatment of
      psychiatric disorders. This Review focuses on the current state of the
      psychiatric diagnostic nosology and recent progress in three areas: genomics,
      neuroimaging, and therapeutics development. The accelerating pace of novel and
      unexpected findings is transforming the understanding of mental illness and
      represents a hopeful sign that the approaches and models that have sustained the
      field for the past 40 years are yielding to a flood of new data and presaging the
      emergence of a new and more powerful scientific paradigm. 

PMID- 24679538
TI  - In search of magic bullets: the golden age of immunotherapeutics.
AB  - Once upon a time, immunology was a black box, inflammatory and autoimmune
      diseases were a mystery, and relatively blunt tools were used to treat these
      diseases. In the last 40 years, advances in molecular biology, DNA recombination
      technology, and genome sequencing allowed immunologists to open the box. As the
      complexity and diversity of the immune response are unveiled, targeted cellular
      and molecular therapies now offer rational approaches to treat immune-mediated
      diseases. Here, we discuss how the tried and true bench-to-bedside strategies
      resulted in some spectacular successes, along with some puzzling failures.
      Conversely, the advent of targeted therapies in the clinic has led to a wealth of
      information that changes how we think about the pathogenesis of immune-mediated
      diseases and how we categorize disease. In turn, these insights can inform next
      generation drug discovery and refine targeted therapies for the appropriate
      patient subsets. 

PMID- 24679539
TI  - Individualized medicine from prewomb to tomb.
AB  - That each of us is truly biologically unique, extending to even monozygotic,
      "identical" twins, is not fully appreciated. Now that it is possible to perform a
      comprehensive "omic" assessment of an individual, including one's DNA and RNA
      sequence and at least some characterization of one's proteome, metabolome,
      microbiome, autoantibodies, and epigenome, it has become abundantly clear that
      each of us has truly one-of-a-kind biological content. Well beyond the allure of
      the matchless fingerprint or snowflake concept, these singular, individual data
      and information set up a remarkable and unprecedented opportunity to improve
      medical treatment and develop preventive strategies to preserve health. 

PMID- 24679541
TI  - Coming full circle-from endless complexity to simplicity and back again.
AB  - Cell has celebrated the powers of reductionist molecular biology and its major
      successes for four decades. Those who have participated in cancer research during
      this period have witnessed wild fluctuations from times where endless
      inexplicable phenomenology reigned supreme to periods of reductionist
      triumphalism and, in recent years, to a move back to confronting the endless
      complexity of this disease. 

PMID- 24679540
TI  - Nuclear Receptors, RXR, and the Big Bang.
AB  - Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and
      thyroid hormone and their structural and functional analysis revealed an
      evolutionarily conserved template for nuclear hormone receptors. This discovery
      sparked identification of numerous genes encoding related proteins, termed orphan
      receptors. Characterization of these orphan receptors and, in particular, of the
      retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the
      "Big Bang" of molecular endocrinology. This Review provides a personal
      perspective on nuclear receptors and explores their integrated and coordinated
      signaling networks that are essential for multicellular life, highlighting the
      RXR heterodimer and its associated ligands and transcriptional mechanism. 

PMID- 24679542
TI  - Non-sinonasal-related olfactory dysfunction: A cohort of 496 patients.
AB  - INTRODUCTION AND AIM: There is a high prevalence of olfactory dysfunction in the
      general population. Several causes of olfactory dysfunction have been reported
      and this disorder is classically divided into sinonasal and non-sinonasal-related
      olfactory dysfunction. The aims of this study were firstly, to evaluate the
      frequency of the various aetiologies of olfactory dysfunction in a population of
      patients with non-sinonasal-related olfactory dysfunction and secondly, to
      evaluate the degree of olfactory impairment associated with these various
      aetiologies. MATERIAL AND METHODS: We retrospectively reviewed a cohort of 496
      patients with non-sinonasal-related olfactory dysfunction. The aetiology of the
      olfactory dysfunction was recorded for each patient. The aetiology was determined
      by a complete clinical assessment, including medical history, complete
      otorhinolaryngological examination, psychophysical testing of olfactory function,
      recording of olfactory event-related potentials and brain magnetic resonance
      imaging. Six groups of patients were defined on the basis of the aetiology of the
      disease and orthonasal and retronasal psychophysical olfactory performances were
      evaluated in each group. RESULTS: Post-infectious and post-traumatic aetiologies
      were the most common causes, representing 37.9% and 33.1% of patients,
      respectively, followed by idiopathic (16.3%), congenital (5.9%), toxic (3.4%) and
      neurological (3.4%) olfactory dysfunction. Anosmia was significantly more
      frequent in congenital (93.1%) and post-traumatic (62.8%) olfactory dysfunction,
      whereas hyposmia was more frequent in the post-infectious group (59.6%).
      Orthonasal and retronasal olfactory function tests were significantly correlated
      in all groups except for the congenital group. CONCLUSIONS: The data of this
      study confirm that the most common causes of non-sinonasal-related olfactory
      dysfunction are post-infectious and post-traumatic. Post-infectious olfactory
      dysfunction is mainly observed in middle-aged women and is mainly associated with
      hyposmia, whereas post-traumatic olfactory dysfunction is mainly observed in
      young men and is associated with a high rate of anosmia.

PMID- 24679544
TI  - A serial 18FDG-PET study of a patient with SSPE who had good prognosis by
      combination therapy with interferon alpha and ribavirin.
AB  - We describe a 15-year-old girl with subacute sclerosing panencephalitis (SSPE) in
      stage II who was treated with isoprinosine, intraventricular interferon alpha
      (IFN-alpha), and ribavirin for 3 years. She is alive at three years from onset
      and studies at school with the assistance of a special educational teacher. To
      assess residual brain function, serial (18)FDG-positron emission tomography (PET)
      was performed three times to measure cortical metabolism: at onset, a year later,
      and three years later. At onset, PET study revealed preserved glucose metabolism
      of the cerebral cortex. In serial PET study, glucose metabolism of the cerebral
      cortex was also preserved even after three years. Although SSPE is a progressive
      disease of the neuronal system, and typically leads to death in approximately 2-3
      years, the neurological prognosis of our case was good. We consider that
      combination therapy in the very early stage without hypometabolism in the
      cerebral cortex may be effective for SSPE. 

PMID- 24679543
TI  - The INDEPTH standard population for low- and middle-income countries, 2013.
AB  - Crude rates such as the crude death rate are functions of both the age-specific
      rates and the age composition of a population. However, differences in the age
      structure between two populations or two time periods can result in specious
      differences in the corresponding crude rates making direct comparisons between
      populations or across time inappropriate. Therefore, when comparing crude rates
      between populations, it is desirable to eliminate or minimize the influence of
      age composition. This task is accomplished by using a standard age structure
      yielding an age-standardized rate. This paper proposes an updated International
      Network for the Demographic Evaluation of Populations and Their Health (INDEPTH)
      standard for use in low- and middle-income countries (LMICs) based on newly
      available data from the health and demographic surveillance system site members
      of the INDEPTH network located throughout Africa and southern Asia. The updated
      INDEPTH standard should better reflect the age structure of LMICs and result in
      more accurate health indicators and demographic rates. We demonstrate use of the
      new INDEPTH standard along with several existing 'world' standards and show how
      resulting age-standardized crude deaths rates differ when using the various
      standard age compositions. 

PMID- 24679545
TI  - Deeper processing is beneficial during episodic memory encoding for adults with
      Williams syndrome.
AB  - Previous research exploring declarative memory in Williams syndrome (WS) has
      revealed impairment in the processing of episodic information accompanied by a
      relative strength in semantic ability. The aim of the current study was to extend
      this literature by examining how relatively spared semantic memory may support
      episodic remembering. Using a level of processing paradigm, older adults with WS
      (aged 35-61 years) were compared to typical adults of the same chronological age
      and typically developing children matched for verbal ability. In the study phase,
      pictures were encoded using either a deep (decide if a picture belongs to a
      particular category) or shallow (perceptual based processing) memory strategy.
      Behavioural indices (reaction time and accuracy) at retrieval were suggestive of
      an overall difficulty in episodic memory for WS adults. Interestingly, however,
      semantic support was evident with a greater recall of items encoded with deep
      compared to shallow processing, indicative of an ability to employ semantic
      encoding strategies to maximise the strength of the memory trace created. Unlike
      individuals with autism who find semantic elaboration strategies problematic, the
      pattern of findings reported here suggests in those domains that are relatively
      impaired in WS, support can be recruited from relatively spared cognitive
      processes. 

PMID- 24679546
TI  - Social support and depression of adults with visual impairments.
AB  - Relatively little research exists with regard to the relationship between social
      support and depression among adults with visual impairments. Such a gap is
      noteworthy when one considers that individuals become more dependent on others as
      they enter middle and late adulthood. The present research will examine the
      association between social networks, social support and depression among adults
      with visual impairments. Seventy-seven adults with visual impairments
      participated in the study. Depression, social network and emotional/practical
      social support were measured with self-report measures. Additionally, the degree
      to which emotional/practical social support received were positive or negative
      and the ability of respondents to self-manage their daily living were assessed.
      Less than a third of respondents scored above the threshold for depressive
      symptoms. Depressive symptoms were not related to gender or vision status.
      Depression was correlated with age, educational level, less positive practical
      support, more negative practical support and more negative emotional support,
      with lower perceptions of self-management representing the most robust predictor
      of depression. Age moderated the relationship between depression and self
      management, and between depression and negative emotional support. Lower
      perceptions of self-management and negative emotional support were significantly
      associated with depressive symptoms. 

PMID- 24679547
TI  - Examining the operant function of challenging behavior in young males with
      fragile X syndrome: a summary of 12 cases.
AB  - This study used experimental functional analyses to examine the operant function
      of challenging behaviors exhibited by 12 males (ages 27-51 months) with fragile X
      syndrome (FXS). Eight children met criteria for negatively reinforced challenging
      behavior in the form of escape from demands and/or escape from social
      interactions. Nine children met criteria for positively reinforced challenging
      behavior in the form of obtaining access to highly preferred items. Attention was
      identified as a maintaining consequence for three children. The functional
      analysis was inconclusive for one child. Results suggest that, for young males
      with FXS, challenging behaviors may more likely be tangibly and escape maintained
      than attention maintained. Our findings affirm past research suggesting a unique
      behavioral phenotype for this population.

PMID- 24679549
TI  - The Model of Care Partner Engagement: use in delirium management.
AB  - Care partner engagement is a central tenant of person-centered care. Despite
      widespread interest in transforming current health care delivery to a more person
      centered system, little is known about effective strategies for engaging care
      partners. The Model of Care Partner Engagement is introduced and described as an
      evidence-informed framework that nurses can use to guide the development of care
      partnerships. The case of hospitalized older adults with cognitive impairment and
      delirium is used to illustrate implementation of the model. Care partner
      engagement is integral to national efforts that promote affordable, equitable,
      high quality care and is a growing expectation of older adults and their
      families. 

PMID- 24679548
TI  - Socioeconomic status, child enrichment factors, and cognitive performance among
      preschool-age children: results from the Follow-Up of Growth and Development
      Experiences study.
AB  - Lower cognitive performance is associated with poorer health and functioning
      throughout the lifespan and disproportionately affects children from lower
      socioeconomic status (SES) populations. Previous studies reporting positive
      associations between child home enrichment and cognitive performance generally
      had a limited distribution of SES. We evaluated the associations of SES and child
      enrichment with cognitive performance in a population with a wide range of SES,
      particularly whether enrichment attenuates associations with SES. Children were
      sampled from a case-control study of small-for-gestational-age (SGA) conducted in
      a public hospital serving a low SES population (final n=198) and a private
      hospital serving a middle-to-high SES population (final n=253). SES (maternal
      education and income) and perinatal factors (SGA, maternal smoking and drinking)
      were obtained from maternal birth interview. Five child home enrichment factors
      (e.g. books in home) and preschool attendance were obtained from follow-up
      interview at age 4.5 years. Cognitive performance was assessed with the
      Differential Ability Scales (DAS), a standardized psychometric test administered
      at follow-up. SES and enrichment scores were created by combining individual
      factors. Analyses were adjusted for perinatal factors. Children from the public
      birth hospital had a significantly lower mean DAS general cognitive ability (GCA)
      score than children born at the private birth hospital (adjusted mean difference 
      21.4, 95% CI: -24.0, -18.7); this was substantially attenuated by adjustment for
      individual SES, child enrichment factors, and preschool attendance (adjusted mean
      difference -5.1, 95% CI: -9.5, -0.7). Individual-level SES score was associated
      with DAS score, beyond the general SES effect associated with hospital of birth.
      Adjustment for preschool attendance and home enrichment score attenuated the
      association between individual SES score and adjusted mean DAS-GCA among children
      born at both of the hospitals. The effect of being in the lower compared to the
      middle tertile of SES score was reduced by approximately a quarter; the effect of
      being in the upper compared to the middle tertile of SES score was reduced by
      nearly half, but this comparison was possible only for children born at the
      private hospital. A child's individual SES was associated with cognitive
      performance within advantaged and disadvantaged populations. Child enrichment was
      associated with better cognitive performance and attenuated the SES influence.
      Health care providers should reinforce guidelines for home enrichment and refer
      children with delays to early intervention and education, particularly children
      from disadvantaged populations. 

PMID- 24679550
TI  - Effects of endurance exercise training on risk components for metabolic syndrome,
      interleukin-6, and the exercise capacity of postmenopausal women.
AB  - We conducted this study to investigate how an exercise program affects the risk
      components of metabolic syndrome (MS), serum interleukin (IL)-6 levels, and
      exercise capacity in postmenopausal women. A randomized clinical trial design was
      used. Women in an exercise group participated in a treadmill-exercise program for
      12 weeks, whereas women in a control group maintained their customary lifestyle.
      Data on variables were collected at baseline and after 12 weeks of the study,
      which was completed by 46 women (mean age, 56.0 +/- 7.0 y). Our results indicate
      endurance exercise exerted significant beneficial effects on waist circumference,
      serum high-density lipoprotein cholesterol (HDL-C) and IL-6 levels, and exercise
      capacity (all P < 0.05). The beneficial effects on IL-6 and exercise capacity
      were correlated with improvements in HDL-C levels (r = -0.33, P = 0.03 and r =
      0.31, P = 0.04, respectively). Our results suggest that health-care providers can
      incorporate an exercise program in treatments to improve the health of
      postmenopausal women.

PMID- 24679551
TI  - [Walking the talk: Quality in the Information Technology era, within the 31st
      SECA Congress].

PMID- 24679552
TI  - Blood docosahexaenoic acid and eicosapentaenoic acid in vegans: Associations with
      age and gender and effects of an algal-derived omega-3 fatty acid supplement.
AB  - BACKGROUND & AIMS: Several studies have demonstrated that vegetarians and vegans
      have much lower plasma concentrations of omega-3 fatty acids (i.e.,
      docosahexaenoic and eicosapentaenoic acids) when compared to those who eat fish.
      The purposes of this study were 1) to define the age and/or sex-specific
      docosahexaenoic plus eicosapentaenoic acids levels in red blood cell membranes
      (expressed as a percent of total fatty acids; hereafter the omega-3 index) in
      long-term vegans, and 2) to determine the effects of a vegetarian omega-3
      supplement (254 mg docosahexaenoic plus eicosapentaenoic acids/day for 4 months)
      on the omega-3 index. METHODS: A sample (n = 165) of vegans was recruited, and
      their omega-3 index was determined using a dried blood spot methodology. A subset
      of 46 subjects with a baseline omega-3 index of <4% was given a vegetarian omega
      3 supplement for 4 months and then retested. RESULTS: The mean +/- SD omega-3
      index was 3.7 +/- 1.0% which was similar to that of a cohort of omnivores
      (deployed US soldiers) from a recently-reported study. Among the vegan cohort,
      the index was significantly higher in females than males (3.9 +/- 1.0% vs. 3.5 +/
      1.0%; p = 0.026) and was directly related to age (p for trend = 0.009). The
      omega-3 index increased from 3.1 +/- 0.6% to 4.8 +/- 0.8% (p = 0.009) in the
      supplementation study. CONCLUSIONS: We conclude that vegans have low baseline
      omega-3 levels, but not lower than omnivores who also consume very little
      docosahexaenoic and eicosapentaenoic acids. The vegans responded robustly to a
      relatively low dose of a vegetarian omega-3 supplement.

PMID- 24679553
TI  - Nutrition care in patients with cancer: A retrospective multicenter analysis of
      current practice - Indications for further studies?
AB  - BACKGROUND & AIMS: Weight loss and malnutrition are frequent problems in oncology
      patients. The aim of this study was to get a perspective of the current practice
      of parenteral nutrition (PN) care in an outpatient setting and to improve patient
      centered nutritional care. METHODS: Fifty-three outpatient oncology centers
      participated in this observational study performed between July 2010 and March
      2011. All participating centers entered data online into a web-based
      documentation form, containing a number of oncology patients, diagnoses, and
      detailed data about oncology patients receiving PN. RESULTS: Two cohorts were
      analyzed. First cohort consisted of all oncology patients in quarter 04/2010.
      Second cohort consisted of patients with PN during the whole studying period. In
      the first cohort 2.46% (n = 626) of 25,424 oncology patients received PN. Most
      frequent diagnoses of patients receiving PN were gastric cancer (n = 119) and
      colorectal cancer (n = 104), however most stated diagnosis was "other" (n = 163).
      In the second cohort (n = 1137), a common indication for PN was impaired
      gastrointestinal passage (n = 177), although here again most stated reason was
      "other" (n = 924). In the course of the PN treatment, patients (n = 1137) showed
      a stable or slowly increasing body mass index (from 21.6 +/- 3.8 kg/m(2) to 21.8
      +/- 3.5 kg/m(2)). CONCLUSION: This is the largest study outlining the
      characteristics of oncology patients in the context of PN in German ambulatory
      centers. They confirm the important role of PN in the care of gastrointestinal
      cancer. Further studies have to be performed to identify if other indications
      than those mentioned in relevant guidelines can trigger initiation of PN.

PMID- 24679554
TI  - Interpreting the evidence: reply to Spruyt et al.

PMID- 24679555
TI  - Moving forward on advance care planning: a novel web site. Commentary on Sudore
      et al.

PMID- 24679556
TI  - Integrating new evidence about an old drug: authors' reply to Franco et al. and
      Bell et al.

PMID- 24679557
TI  - APIC's continuing efforts to help members.

PMID- 24679558
TI  - Are community environmental surfaces near hospitals reservoirs for gram-negative
      nosocomial pathogens?
AB  - BACKGROUND: Hospital visitors and staff visit neighboring businesses, creating
      the potential for contamination of surfaces with hospital flora. METHODS:
      Cultures were obtained from environmental surfaces in hospital lobbies and the
      surrounding community of 6 hospitals in Brooklyn, NY. As a control, cultures were
      taken from surfaces >1.5 miles from any hospital. Screening for beta-lactamases
      was done by polymerase chain reaction (PCR), and select isolates were
      fingerprinted by the repetitive extragenic palindromic sequence-PCR method.
      RESULTS: Of 493 cultures, most (70%) involved doors from local businesses.
      Cephalosporin-resistant Citrobacter freundii (n = 3), Escherichia coli (n = 2),
      and Enterobacter sp (n = 2) were recovered from surfaces near hospitals, but not
      from control sites. One isolate of Stenotrophomonas maltophilia harbored an
      integron-associated VIM-2. Acinetobacter baumannii was recovered in 15 samples,
      including 4.5% of swabs from <=0.5 miles of the hospitals versus 0% from >=0.6
      miles (P = .004). Eleven A baumannii isolates were clonally related by repetitive
      extragenic palindromic sequence-PCR and were also related to a known clinical
      isolate. CONCLUSIONS: Strains of A baumannii and cephalosporin-resistant
      Enterobacteriaceae can be recovered from environmental surfaces surrounding
      hospitals. Finding these pathogens in the perihospital environment suggests hand
      cleansing should be emphasized for all people entering and leaving hospitals. The
      finding of integron-associated VIM-2 in our region is disconcerting, and further
      vigilance is warranted.

PMID- 24679559
TI  - Working relationships of infection prevention and control programs and
      environmental services and associations with antibiotic-resistant organisms in
      Canadian acute care hospitals.
AB  - BACKGROUND: Environmental contamination in hospitals with antibiotic-resistant
      organisms (AROs) is associated with patient contraction of AROs. This study
      examined the working relationship of Infection Prevention and Control (IPAC) and
      Environmental Services and the impact of that relationship on ARO rates. METHODS:
      Lead infection control professionals completed an online survey that assessed the
      IPAC and Environmental Services working relationship in their acute care hospital
      in 2011. The survey assessed cleaning collaborations, staff training, hospital
      cleanliness, and nosocomial methicillin-resistant Staphylococcus aureus (MRSA)
      infection, vancomycin-resistant Enterococcus (VRE) infection, and Clostridium
      difficile infection (CDI). RESULTS: The survey was completed by 58.3% of
      hospitals (119 of 204). Two-thirds (65.8%; 77 of 117) of the respondents reported
      that their cleaners were adequately trained, and 62.4% (73 of 117) reported that
      their hospital was sufficiently clean. Greater cooperation between IPAC and
      Environmental Services was associated with lower rates of MRSA infection (r = 
      0.22; P = .02), and frequent collaboration regarding cleaning protocols was
      associated with lower rates of VRE infection (r = -0.20; P = .03) and CDI (r = 
      0.31; P < .001). CONCLUSIONS: Canadian IPAC programs generally had collaborative
      working relationships with Environmental Services, and this was associated with
      lower rates of ARO. Deficits in the adequacy of cleaning staff training and
      hospital cleanliness were identified. The promotion of collaborative working
      relationships and additional training for Environmental Services workers would be
      expected to lower ARO rates.

PMID- 24679560
TI  - State focus on health care-associated infection prevention in nursing homes.
AB  - BACKGROUND: Despite increased focus on health care-associated infections (HAI),
      between 1.6 and 3.8 million HAI occur annually among the vulnerable population
      residing in US nursing homes (NH). This study characterized state department of
      health (DOH) activities and policies intended to improve quality and reduce HAI
      in NH. METHODS: We created a 17-item standardized data collection tool informed
      by 20 state DOH Web sites, reviewed by experts in the field and piloted by 2
      independent reviewers (Cohen's kappa .45-.73). The tool and corresponding
      protocol were used to systematically evaluate state DOH Web sites and related
      links. RESULTS: Three categories of data were abstracted: (1) consumer-directed
      information intended to increase accountability of and competition between NH,
      including mandatory HAI reporting and NH inspection reports; (2) surveyor
      training for federally-mandated NH inspections; and (3) guidance for NH providers
      to prevent HAI and monitor incidence. Only 5 states included HAI reporting in NH
      with differing HAI types and reporting requirements. CONCLUSION: State DOH
      information and activities focused on NH quality and reducing HAI were
      inconsistent. Systematically characterizing state DOH efforts to reduce HAI in NH
      is important to interpret the effects of these activities.

PMID- 24679561
TI  - The silver lining of disposable sporicidal privacy curtains in an intensive care
      unit.
AB  - BACKGROUND: The environment is a well-known source of health care-acquired
      infection. Because of the known risk of contamination, patient privacy curtains
      require frequent changes to decrease the risk of spread from patients to curtain
      and visa versa. METHODS: Fourteen disposable sporicidal privacy curtains were
      tested from December 2012 to June 2013 while hanging in a busy intensive care
      unit. Significant bacterial pathogens were identified and total bacteria
      enumerated as colony-forming units. Antimicrobial activity of curtain swatches
      was also tested against a range of bacteria in the laboratory. Measurements were
      recorded as zone of inhibition and contact inhibition. A cost analysis to replace
      standard curtains with disposable sporicidal curtains was also undertaken.
      RESULTS: Cultures grew low numbers of skin and environmental microorganisms with
      no methicillin-resistant Staphylococcus aureus, carbapenem-resistant
      Enterobacteriaceae, or Clostridium difficile detected. Vancomycin-resistant
      enterococci were recovered in very low numbers from 2 curtains where vancomycin
      resistant enterococci-infected patients had been located. Privacy curtains
      demonstrated antimicrobial activity against C difficile and 13 additional
      bacterial pathogens. CONCLUSION: We conclude that disposable sporicidal privacy
      curtains are cost-effective and best replaced at 6 months in a high-risk area
      such as an intensive care unit.

PMID- 24679562
TI  - Barriers and facilitators to influenza vaccination and vaccine coverage in a
      cohort of health care personnel.
AB  - BACKGROUND: Annual influenza vaccination is recommended for health care personnel
      (HCP). We describe influenza vaccination coverage among HCP during the 2010-2011
      season and present reported facilitators of and barriers to vaccination. METHODS:
      We enrolled HCP 18 to 65 years of age, working full time, with direct patient
      contact. Participants completed an Internet-based survey at enrollment and the
      end of influenza season. In addition to self-reported data, we collected
      information about the 2010-2011 influenza vaccine from electronic employee health
      and medical records. RESULTS: Vaccination coverage was 77% (1,307/1,701). Factors
      associated with higher vaccination coverage include older age, being married or
      partnered, working as a physician or dentist, prior history of influenza
      vaccination, more years in patient care, and higher job satisfaction. Personal
      protection was reported as the most important reason for vaccination followed
      closely by convenience, protection of patients, and protection of family and
      friends. Concerns about perceived vaccine safety and effectiveness and low
      perceived susceptibility to influenza were the most commonly reported barriers to
      vaccination. About half of the unvaccinated HCP said they would have been
      vaccinated if required by their employer. CONCLUSION: Influenza vaccination in
      this cohort was relatively high but still fell short of the recommended target of
      90% coverage for HCP. Addressing concerns about vaccine safety and effectiveness
      are possible areas for future education or intervention to improve coverage among
      HCP.

PMID- 24679564
TI  - Development and psychometric testing of ventilator bundle questionnaire and
      observation schedule.
AB  - BACKGROUND: There is a current lack of valid and reliable instruments that can be
      used to examine critical care nurses' knowledge and skills in adhering to
      ventilator bundles. The aim of this study was to develop and psychometrically
      test a ventilator bundle questionnaire (VBQ) and ventilator bundle observation
      schedule (VBOS). METHODS: The VBQ and VBOS consisted of a list of pharmacologic
      and nonpharmacologic nurse-led interventions taken from the literature and
      supported by various levels of evidence. After content validation, stability and
      equivalence reliabilities of the VBOS were determined in a randomly selected
      sample of critical care nurses from a single academic center in Finland. RESULTS:
      The final VBQ contained 49 multiple-choice questions, and the VBOS had 86
      dichotomous items, whose overall content validity ranged from 0.99 to 1.0. The
      overall intraclass correlation coefficient of the VBOS ranged from 0.93 to 1.0.
      CONCLUSIONS: The VBQ and VBOS have acceptable psychometric properties and could
      be used to objectively assess whether evidence-based guidelines regarding
      ventilator bundles are being used in clinical practice. Further testing with
      diverse samples is needed to strengthen the validity and reliability of these
      instruments.

PMID- 24679563
TI  - Long-term carriage of Klebsiella pneumoniae carbapenemase-2-producing K
      pneumoniae after a large single-center outbreak in Germany.
AB  - BACKGROUND: The natural progress of intestinal colonization with Klebsiella
      pneumoniae carbapenemase-2-producing K pneumoniae (KPC-2-KP) is almost unknown.
      METHODS: After a large, single-center outbreak of KPC-2-KP, we analyzed carrier
      prevalence through retrospective and prospective investigation of intestinal KPC
      2-KP carriage 1 month, 3 months, 6 months, 1 year, and 2 years after acquisition,
      defined as the earliest date of KPC-2-KP detection. Rectal swabs or stool samples
      were collected at baseline and at each visit and submitted for both culture and
      KPC-specific polymerase chain reaction. Resolution of intestinal KPC-2-KP
      carriage was defined as a minimum of 3 consecutive negative polymerase chain
      reaction test results separated by at least 48 hours. RESULTS: In patients
      available for long-term evaluation 26 out of 84 patients (31%) tested negative
      for KPC-2-KP after 1 month, 14 out of 34 (41%) after 3 months, 17 out of 26 (65%)
      after 6 months, 14 out of 19 (74%) after 1 year, and 5 out of 6 (83%) after 2
      years. Decolonization of KPC-2-KP was hampered in patients with prolonged or
      repeated hospitalization (P = .044-.140, depending on the time interval). Two
      patients retested positive for KPC-2-KP after they had previously shown 3
      consecutive negative tests. The longest positive KPC-2-KP carrier status so far
      was observed after nearly 40 months (1,191 days). CONCLUSIONS: The majority of
      patients experienced spontaneous decolonization within 6 months after
      acquisition, mainly after discharge from the hospital. However, long-term
      carriage of >3 years is possible. Appropriate infection control measures must be
      taken when these patients are readmitted to health care facilities. A series of
      at least 4 consecutive negative rectal swabs or stool samples separated by
      sufficient time intervals appears necessary before the declaration of successful
      KPC-2-KP decolonization is made.

PMID- 24679565
TI  - Effectiveness of an outpatient preoperative care bundle in preventing
      postoperative pneumonia among esophageal cancer patients.
AB  - BACKGROUND: This historical case-control study examined the effectiveness of an
      outpatient preoperative care bundle on the incidence of postoperative pneumonia
      among patients with esophageal cancer. METHODS: We implemented a preoperative
      care bundle that comprised 7 care procedures that previous studies had suggested
      to be effective for decreasing postoperative respiratory complications,
      infections, postoperative hospital stay, and mortality. The care bundle group
      included patients who underwent surgery after the care bundle was implemented,
      whereas the control group included those who underwent surgery before its
      implementation. RESULTS: The incidence of postoperative pneumonia was 3.8% in the
      care bundle group (1/26) and 22.4% in the control group (48/214). A logistic
      regression model showed that implementation of the care bundle had a significant
      effect on prevention of postoperative pneumonia (odds ratio, 0.16; 95% confidence
      interval: 0.01-0.94) after controlling the following confounding factors: sex,
      blood urea nitrogen, amount of blood loss, recurrent laryngeal nerve palsy, and
      preoperative hospital stay. CONCLUSION: Implementation of the procedures of the
      preoperative care bundle was shown to be effective for preventing postoperative
      pneumonia in patients with esophageal cancer.

PMID- 24679566
TI  - Identification of temporal clusters and risk factors of bacteremia by nosocomial
      vancomycin-resistant enterococci.
AB  - BACKGROUND: This study aimed to evaluate a different methodology for addressing
      the evolution of nosocomial bacteremia by vancomycin-resistant enterococci (VRE)
      in a hospital setting. METHODS: In this retrospective cohort study, data were
      collected from the date of first registration up to December 2008 from the
      electronic medical records of patients with VRE bacteremia in a school hospital.
      RESULTS: Thirty cases of VRE bacteremia and 274 cases of vancomycin-susceptible
      enterococci (VSE) bacteremia were identified. The average age of the patients was
      56 years. The rates of Enterococcus faecium and Enterococcus faecalis in the
      hospital's intensive care unit (ICU) and wards showed no statistically
      significant differences. The risk of acquiring VRE bacteremia was at least 3-fold
      higher in the ICU than in the wards. The risk of death was 2.73-fold higher in
      patients with VRE bacteremia compared with those with VSE bacteremia. Only one
      temporal cluster statistically significant of VRE bacteremia was found in the
      study period. CONCLUSIONS: The identification of temporal clusters can be an
      important tool to optimize health actions and thereby reduce the burden of
      operating costs.

PMID- 24679567
TI  - Major biologic characteristics of Acinetobacter baumannii isolates from hospital
      environmental and patients' respiratory tract sources.
AB  - BACKGROUND: This prospective study investigated major biologic characteristics of
      Acinetobacter baumannii isolates from hospital environment and respiratory tract
      samples of patients admitted to adult intensive care units (ICUs) at the Jordan
      University Hospital. METHODS: A baumannii isolates from both sources were
      examined for antimicrobial susceptibility and for presence of specific metallo
      beta-lactamase genes (VIM-2, IMP-1) and OXA-type beta-lactamase genes (OXA-type)
      using polymerase chain reaction and biofilm formation and surviving under various
      temperatures and pH conditions. RESULTS: The majority of A baumannii isolates
      from environmental and patients sources was multidrug resistant (MDR), except for
      colistin and tigecycline. All A baumannii examined carried a blaOXA51-like gene,
      58% has a blaOXA23-like gene, and 38.8% has a blaOXA24-like gene. Representative
      MDR A baumannii isolates from both sources were capable to form biofilm. A
      baumannii environmental isolates were capable to survive for a longer time in
      tap, normal saline, and distilled water than respiratory tract isolates with pH
      range of 4.5 to 8 and temperature between 18 degrees C to 37 degrees C.
      CONCLUSIONS: This study demonstrates that A baumannii isolates from the patients'
      respiratory tract and hospital environment carried much similar multidrug
      resistance patterns and biologic characteristics. In conclusion, this study shows
      that all MDR A baumannii strains survived well in the hospital environment,
      especially in water and moist environment and produced biofilm, which might be
      responsible for high colonization in the respiratory tract of patients in ICU.

PMID- 24679568
TI  - Prevention of gram-positive infections in peritoneal dialysis patients in Hong
      Kong: a cost-effectiveness analysis.
AB  - BACKGROUND: Gram-positive bacteria are the major causative pathogens of
      peritonitis and exit site infection in patients undergoing peritoneal dialysis
      (PD). We investigated the cost-effectiveness of regular application of mupirocin
      at the exit site in PD recipients from the perspective of health care providers
      in Hong Kong. METHODS: A decision tree was designed to simulate outcomes of
      incident PD patients with and without regular application of mupirocin over a 1
      year period. Outcome measures included total direct medical costs, quality
      adjusted life-years (QALYs) gained, and gram-positive infection-related mortality
      rate. Model inputs were derived from the literature. Sensitivity analyses
      evaluated the impact of uncertainty in all model variables. RESULTS: In a base
      case analysis, the mupirocin group had a higher expected QALY value (0.6496 vs
      0.6456), a lower infection-related mortality rate (0.18% vs 1.64%), and a lower
      total cost per patient (US $258 vs $1661) compared with the control group. The
      rate of gram-positive peritonitis without mupirocin and the risk of gram-positive
      peritonitis with mupirocin were influential factors. In 10,000 Monte Carlo
      simulations, the mupirocin group had significantly lower associated costs, higher
      QALYs, and a lower mortality rate 99.9% of the time. CONCLUSIONS: Topical
      mupirocin appears to be a cost-effective preventive measure against gram-positive
      infection in incident patients undergoing PD. The cost-effectiveness of mupirocin
      is affected by the level of infection risk reduction and subject to resistance
      against mupirocin.

PMID- 24679571
TI  - Decreasing cesarean section surgical site infection: an ongoing comprehensive
      quality improvement program.
AB  - This report illustrates how the "plan-do-study-act" method of continuous quality
      improvement can be effective in reducing surgical site infection after cesarean
      delivery. 

PMID- 24679569
TI  - The survival of influenza A(H1N1)pdm09 virus on 4 household surfaces.
AB  - We investigated the survival of a pandemic strain of influenza A H1N1 on a
      variety of common household surfaces where multiple samples were taken from 4
      types of common household fomite at 7 time points. Results showed that influenza
      A H1N1sw virus particles remained infectious for 48 hours on a wooden surface,
      for 24 hours on stainless steel and plastic surfaces, and for 8 hours on a cloth
      surface, although virus recovery from the cloth may have been suboptimal. Our
      results suggest that pandemic influenza A H1N1 can survive on common household
      fomites for extended periods of time, and that good hand hygiene and regular
      disinfection of commonly touched surfaces should be practiced during the
      influenza season to help reduce transmission.

PMID- 24679570
TI  - Effectiveness of improved hydrogen peroxide in decontaminating privacy curtains
      contaminated with multidrug-resistant pathogens.
AB  - We tested the ability of an improved hydrogen peroxide solution to decontaminate
      privacy curtains in inpatient and outpatient areas. The microbial contamination
      of the curtains was assessed before and after the curtains were sprayed with
      improved hydrogen peroxide. The disinfectant reduced the microbial load on the
      privacy curtains by 96.8% in 37 patient rooms. 

PMID- 24679572
TI  - A polymicrobial outbreak of surgical site infections following cardiac surgery at
      a community hospital in Florida, 2011-2012.
AB  - We describe an outbreak of 22 sternal surgical site infections following cardiac
      surgery, including 4 Gordonia infections. Possible operation room environmental
      contamination and suboptimal infection control practices regarding scrub attire
      may have contributed to the outbreak. 

PMID- 24679573
TI  - Occurrence of nosocomial methicillin-resistant Staphylococcus aureus as a marker
      for transmission in a surgical intensive care unit in China.
AB  - In 2008, an intensive care unit (ICU) in a large Chinese hospital was moved from
      a 6-bed old ward to a 20-bed new ward. After the move, the prevalence of
      methicillin-resistant Staphylococcus aureus (MRSA) in patients and environmental
      sites decreased significantly, but the number of ICU-acquired cases per imported
      MRSA case increased from 1.4 to 4.1. This study suggests that the nurse cohorting
      level and hand hygiene compliance are strong predicators of MRSA transmission in
      ICUs. 

PMID- 24679574
TI  - Patient-as-observer approach: an alternative method for hand hygiene auditing in
      an ambulatory care setting.
AB  - A survey pilot asked patients to observe the hand hygiene compliance of their
      health care providers. Patients returned 75.1% of the survey cards distributed,
      and the overall hand hygiene compliance was 96.8%. Survey results and patient
      commentary were used to motivate hand hygiene compliance. The patient-as-observer
      approach appeared to be a viable alternative for hand hygiene auditing in an
      ambulatory care setting because it educated, engaged, and empowered patients to
      play a more active role in their own health care. 

PMID- 24679575
TI  - Hand sanitizer-dispensing door handles increase hand hygiene compliance: a pilot
      study.
AB  - Improving rates of hand hygiene compliance (HHC) has been shown to reduce
      nosocomial disease. We compared the HHC for a traditional wall-mounted unit and a
      novel sanitizer-dispensing door handle device in a hospital inpatient ultrasound
      area. HHC increased 24.5%-77.1% (P < .001) for the exam room with the sanitizer
      dispensing door handle, whereas it remained unchanged for the other rooms.
      Technical improvements like a sanitizer-dispensing door handle can improve
      hospital HHC. 

PMID- 24679576
TI  - Influenza-like illness and presenteeism among school employees.
AB  - We determined the prevalence of influenza-like illness (ILI) among employees of a
      suburban Ohio school district. In a survey of 412 of 841 employees (49%), 120
      (29%) reported ILI symptoms during the school year, and 92 (77%) reported working
      while ill. Age >=50 years and asthma were significantly associated with reporting
      of ILI symptoms. Encouraging school employees to receive the seasonal influenza
      vaccine and to stay home when ill should be part of a comprehensive influenza
      prevention strategy. 

PMID- 24679577
TI  - Idle central venous catheter-days pose infection risk for patients after
      discharge from intensive care.
AB  - This prospective observational study measured idle central venous catheter (CVC)
      days (no medical indication), and ward clinicians' adherence to evidence-based
      practices for preventing short-term central line-associated bloodstream
      infections (CLABSIs). In 340 patients discharged from ICU over a 1-year period,
      208 of 794 CVC-days (26.2%) were idle. Interventions to prevent CLABSIs were
      poorly implemented. Ward clinicians need education regarding risk management
      strategies to prevent CLABSIs, and clear accountability processes for prompt
      catheter removal are recommended. 

PMID- 24679578
TI  - Outbreak of AmpC beta-lactamase-hyper-producing Enterobacter cloacae in a
      neonatal intensive care unit in a French teaching hospital.
AB  - We report the investigation of an outbreak of colonization by a wild-type
      Enterobacter cloacae and its AmpC-hyper-producing derivative E cloacae in a
      neonatal intensive care unit. E cloacae hyper-producing AmpC beta-lactamase
      isolates were found from neonate specimens and from environmental samples. All
      the isolates belonged to the same clone. 

PMID- 24679579
TI  - Incidence of infection in orthopedic surgeries: do we actually know it?

PMID- 24679580
TI  - Fabric softeners impact cleaning, but not disinfection, by a saturated steam
      vapor system.

PMID- 24679581
TI  - Absence of an intervention effect following central line bundle implementation in
      an intensive care unit: An interpretation.

PMID- 24679582
TI  - Environment and body contamination: a comparison of two different removal methods
      in three types of personal protective clothing.
AB  - BACKGROUND: This study aimed to examine the body contamination rates and
      environmental contamination levels during the removal of 3 types of personal
      protective clothing (PPC) by the individual accustomed removal method (IARM) and
      gown removal methods recommended by the Centers for Disease Control and
      Prevention (CDC). METHODS: Fifty participants performed IARM and CDC-recommended
      gown removal methods to remove 3 types of PPC (ie, cotton gown, water resistant
      gown, and plastic apron) in random order at 2 separate sessions after applying
      Glo Germ simulated germ lotion on the gown's surface. A video demonstrating the
      CDC-recommended gown removal method was shown between the 2 sessions. After PPC
      removal, fluorescent stains were counted by an ultraviolet scan under dim light.
      RESULTS: Following IARM, contaminants were splashed in the surroundings,
      particularly on the front part of the subject. The plastic apron and cotton gown
      obtained the highest and lowest contaminative hazards, respectively, to the
      hands, shoes, and environment. Females, nurses, and senior staff had serious hand
      or shoe contamination. The CDC removal method more significantly reduced body and
      environmental contamination of small fluorescent stains (<1 cm(2)), but not of
      large patches (>1 cm(2)), than IARM. CONCLUSION: The effect of gown removal, PPC
      type, discarding PPC location, training of infection control measures, hand
      hygiene, and special work shoes should be considered daily.

PMID- 24679583
TI  - Evaluating the quality of outbreak reports on health care-associated infections
      in Sao Paulo, Brazil, during 2000-2010 using the ORION statement findings and
      recommendations.
AB  - BACKGROUND: The standard of outbreak reports must be improved to a level where
      they are robust enough to properly influence preventive strategies. We aimed to
      verify compliance with mandatory outbreak notification, describing epidemiologic
      characteristics and management, and evaluating the quality of outbreak reports on
      health care-associated infections in Sao Paulo State, Brazil. METHODS: A
      systematic search was carried out on PubMed, the Latin American and Caribbean
      Health Sciences Literature database, Embase, Outbreak Database, the Annals of
      Brazilian Conferences on Healthcare-Associated Infection Prevention and
      Infectious Diseases, and reports from the Sao Paulo State Hospital Infection
      Division. The quality of reports was evaluated according to the Outbreak Reports
      and Intervention studies of Nosocomial Infection (ORION) statement guidelines.
      RESULTS: A total of 87 outbreak reports were identified; however, only 15
      outbreaks (17.2%) were reported to the Sao Paulo State Hospital Infection
      Division. Bloodstream infection and neonatal intensive care units were mostly
      implicated (23% and 19.5%, respectively). Quality, evaluated according to ORION
      statement recommendations, was generally poor. The ORION categories of
      Background, Objectives, Participants, Setting, Infection-Related Outcomes, and
      Generality were properly described in 32.2%, 74.7%, 2.3%, 46%, 2.3%, and 12.6% of
      reports, respectively. Interventions and Culture-Typing were described with
      details in 51.9% and 55.2% of outbreak reports, respectively. CONCLUSIONS: Our
      findings pointed out the need for strategies to improve competence in outbreak
      reports, and the ORION statement guidelines may help in this matter. Efforts to
      promote confidence and consequent compliance with mandatory notification of
      outbreak reports are essential.

PMID- 24679584
TI  - Single-phase and two-phase anaerobic digestion of fruit and vegetable waste:
      comparison of start-up, reactor stability and process performance.
AB  - Single-phase and two-phase digestion of fruit and vegetable waste were studied to
      compare reactor start-up, reactor stability and performance (methane yield,
      volatile solids reduction and energy yield). The single-phase reactor (SPR) was a
      conventional reactor operated at a low loading rate (maximum of 3.5 kgVS/m3 d),
      while the two-phase system consisted of an acidification reactor (TPAR) and a
      methanogenic reactor (TPMR). The TPAR was inoculated with methanogenic sludge
      similar to the SPR, but was operated with step-wise increase in the loading rate
      and with total recirculation of reactor solids to convert it into acidification
      sludge. Before each feeding, part of the sludge from TPAR was centrifuged, the
      centrifuge liquid (solubilized products) was fed to the TPMR and centrifuged
      solids were recycled back to the reactor. Single-phase digestion produced a
      methane yield of 0.45 m3 CH4/kg VS fed and VS removal of 83%. The TPAR shifted to
      acidification mode at an OLR of 10.0 kgVS/m3 d and then achieved stable
      performance at 7.0 kgVS/m3 d and pH 5.5-6.2, with very high substrate
      solubilization rate and a methane yield of 0.30 m3 CH4/kg COD fed. The two-phase
      process was capable of high VS reduction, but material and energy balance showed
      that the single-phase process was superior in terms of volumetric methane
      production and energy yield by 33%. The lower energy yield of the two-phase
      system was due to the loss of energy during hydrolysis in the TPAR and the
      deficit in methane production in the TPMR attributed to COD loss due to biomass
      synthesis and adsorption of hard COD onto the flocs. These results including the
      complicated operational procedure of the two-phase process and the economic
      factors suggested that the single-phase process could be the preferred system for
      FVW.

PMID- 24679585
TI  - NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony
      formation by bone marrow mononuclear cells from high-risk myelodysplastic
      syndrome patients.
AB  - JAK2/STAT signaling promotes survival and expansion of myelodysplastic syndrome
      (MDS) clones, but little is known about the potential of JAK2/STAT as a
      therapeutic target in MDS. We investigated the effect of NS-018, a novel
      antagonist for JAK2, on the colony-forming ability of bone marrow mononuclear
      cells (BMMNCs) from high-risk MDS patients. NS-018 decreased colony-forming unit
      granulocyte/macrophage (CFU-GM) colony numbers from MDS-derived BMMNCs in a dose
      dependent manner, and this effect was significantly more potent than against
      normal BMMNCs. In addition, NS-018 suppressed the phosphorylation of STAT3 in
      colony-forming cells from MDS patients. Collectively, NS-018 could be a new
      therapeutic option for high-risk MDS. 

PMID- 24679586
TI  - IL2/IL-4, OX40L and FDC-like cell line support the in vitro tumor cell growth of
      adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with an
      extremely poor prognosis. Maintaining ATLL cells in vitro is difficult and little
      is known about how they maintain themselves or grow in patients. Elucidating the
      interaction between ATLL cells and surrounding host factors might therefore
      provide important insights into pathophysiology. We cultured primary ATLL cells
      in various culture conditions using IL-2, IL-4 and feeder cells, and established
      two cell lines dependent on IL-2, IL-4 and a follicular dendritic cell-derived
      cell line, HK, in which OX40-ligand was induced. Our study indicates the
      importance of microenvironment in the homeostasis of ATLL. 

PMID- 24679587
TI  - Sequence and structural analyses of NSP4 proteins from human group A rotavirus
      strains detected in Tunisia.
AB  - BACKGROUND: The NSP4 protein of group A rotavirus (RVA) has been recognized as a
      viral enterotoxin and plays important roles in viral pathogenesis and
      morphogenesis. Domains involved in structural and functional interactions have
      been proposed mainly based on the simian SA11 strain. METHODS: NSP4 has been
      classified into 15 different genotypes (E1-E15), and the aim of this study was to
      analyze the sequences of 46 RVA strains in order to determine the aminoacid (aa)
      differences between E1 and E2 genotypes. Another aspect was to characterize the
      structural and physicochemical properties of these strains. RESULTS: Comparison
      of deduced aa sequences of the NSP4 protein showed that divergences between NSP4
      genotypes E1 and E2 were mostly observed in the VP4-binding, the interspecies
      variable domain (ISVD) and the double-layered particle (DLP) binding domains.
      Interestingly, uncommon variations in residues 131 and 138, which are known to be
      important aa in pathogenesis, were found in one unusual animal derived strain
      belonging to the E2 genotype. Concerning the structural aspect, no significant
      differences were noted. CONCLUSION: The presence of punctual aa variations in the
      NSP4 genotypes may indicate that NSP4 mutates mainly via accumulation of point
      mutations.

PMID- 24679588
TI  - The function of elastic fibers in the arteries: beyond elasticity.
AB  - The main components of elastic fibers, elastin and fibrillin-containing
      microfibrils play a structural and mechanical role in the arteries and their
      essential function is to provide elasticity and resilience to the tissues.
      However, through control of the quiescent contractile phenotype of arterial
      smooth muscle cells, elastin also acts as an autocrine factor and, via the
      binding of 'latent transforming growth factor (TGF)-beta binding protein (LTBP) -
      latency-associated peptide (LAP) - TGF-beta' complexes, fibrillins regulate the
      activation and availability of TGF-betas. These recent discoveries are detailed
      in this review. 

PMID- 24679589
TI  - Cross talk between the extracellular matrix and the immune system in the context
      of endocrine pancreatic islet transplantation. A review article.
AB  - This review aims to highlight the importance of the bidirectional influence of
      the extracellular matrix (ECM) and immune cells in the context of type 1 diabetes
      mellitus (T1DM) and endocrine pancreatic islet transplantation. We introduced the
      main classes of molecules and proteins constituting the ECM as well as cells and
      cytokines of the immune system with the aim to further examine their roles in
      T1DM and islet transplantation. Integrins expressed by immune cells and their
      functions are detailed. Finally, this article reviews the roles of the ECM and
      the immune system in islet transplantation as well as ECM-related cytokines and
      their influence on the ECM and immune cells. 

PMID- 24679590
TI  - Occurrence of micropollutants in four major rivers in Korea.
AB  - There has been an increasing concern in recent years over the presence of
      numerous micropollutants in river water. Simultaneously, risk assessment of
      micropollutants has become increasingly important due to their high toxicity.
      Therefore, the aims of this study were to characterize the levels of
      micropollutants in rivers, to identify the sources of these pollutants, and to
      evaluate their risk quotients (RQ) to the ecological system. Monitoring data from
      159 sites distributed across four major rivers in Korea were collected from the
      Ministry of the Environment (KME) reports. Tests were performed to check for the
      presence of 35 pollutants in river waters, from which 29 pollutants were
      detected. Organochlorine pesticides (OCPs) occurred most frequently, at low
      concentrations, whereas volatile organic compounds (VOCs) and phthalates were
      detected at higher concentrations. Based on this study, it was suggested that the
      factories near the sampling sites where pollutants were found represent one of
      the main sources of chemicals. After comparing the industrial activities with the
      measured pollutants, although the released amounts were not reported,
      representative intermediate chemicals were found in the river water. The RQs of
      most VOCs were below one, despite their concentration range being higher,
      compared with other pollutants. Methyl bromide and di-n-octyl phthalate occurred
      frequently in the Han River Basin and the Nakdong River Basin, respectively, and
      their RQs were consistently high, so further studies should focus on their exact
      emission source in order to reduce ecological risk. The results suggest that it
      will be necessary to develop methods of risk assessment that are more tailored to
      the various micropollutants present in river water, in addition to the
      implementation of water treatment systems to reduce ecological risk. 

PMID- 24679591
TI  - Dental caries, cariogenic microorganisms and salivary properties of allergic
      rhinitis children.
AB  - OBJECTIVES: The aim of this study was to observe the caries activities of
      allergic rhinitis patients in relation to salivary properties, salivary levels of
      mutans streptococci (MS) and lactobacillus (LB), oral hygiene and dietary habits.
      METHODS: The study groups composed of 40 allergic rhinitis children and 40
      healthy controls aged between 6 and 13 years old. Demographic data, oral hygiene
      practices and dietary habits were recorded by questionnaire. For permanent teeth,
      caries experience was expressed as DMFT (D=decayed; M=missing; F=filled; T=teeth)
      index. The dmft (d=decayed; m=missing; f=filling; t=teeth) index was used for
      caries prevalence in primary teeth. Unstimulated salivary flow rate, salivary
      buffering capacity, and salivary MS and LB were also determined in children with
      allergic rhinitis and controls. RESULTS: There were no significant differences in
      combined DMFT/dmft, salivary flow rate, buffer capacity of saliva, salivary LB
      levels, and sugary food consumption between cases and controls (p>0.05). However,
      higher salivary MS levels were observed in allergic rhinitis patients, compared
      to controls (P<0.05). CONCLUSIONS: Our results demonstrated that patients with
      allergic rhinitis had an increase in the level of salivary MS.

PMID- 24679593
TI  - The evolution of violence risk assessment.
AB  - Many instruments have been published in recent years to improve the ability of
      mental health clinicians to estimate the likelihood that an individual will
      behave violently toward others. Increasingly, these instruments are being applied
      in response to laws that require specialized risk assessments. In this review, we
      present a framework that goes beyond the "clinical" and "actuarial" dichotomy to
      describe a continuum of structured approaches to risk assessment. Despite
      differences among them, there is little evidence that one instrument predicts
      violence better than another. We believe that these group-based instruments are
      useful for assessing an individual's risk, and that the instrument should be
      chosen based on the purpose of the assessment. 

PMID- 24679592
TI  - Direction of single obstacle circumvention in middle-aged children.
AB  - When required to walk around a stationary object, adults use the location of the
      goal to set up their locomotor axis and obstacles presented along the locomotor
      axis will repel the individual towards the side that affords more space [1].
      Research has yet to examine whether children can identify the locomotor axis and
      choose their paths accordingly. Therefore, the current study examined the factors
      that influence the direction in which children choose to deviate around a single
      obstacle and whether the presence or absence of a goal influences path selection
      and trajectory. Ten children (age: 7.1 years+/-0.8) walked along a 9 m path and
      avoided a single obstacle that was located in one of three locations (midline, 15
      cm to the right or 15 cm to the left). On half the trials, an end-goal was
      visible from the start of the path while the other half of the trials had no
      visible goal. The results demonstrate that: (1) children are able to perceive and
      move towards more open space but are more variable when the end-goal is not
      visible; (2) children are capable of maintaining an elliptical-shaped protective
      envelope when avoiding a single obstacle regardless of whether or not the
      locomotor axis is established; and (3) although children are capable of choosing
      paths that afford the most space, the manner in which they arrive at their goal
      is not driven by factors similar to adults.

PMID- 24679594
TI  - Effects of inoculum source, pH, redox potential and headspace di-hydrogen on
      rumen in vitro fermentation yields.
AB  - This in vitro study aimed at understanding how abiotic, that is chemical and
      electrochemical potentials, and biotic factors combine to impact the outputs of
      rumen volatile fatty acid (VFA). Using a 48-run design optimized by means of an
      exchange algorithm, the curvilinear effects of pH, Eh and partial pressure of
      dihydrogen (H2) on fermentation yields were investigated in 6-h batch cultures of
      mixed rumen microbes, fed on glucose so as to bypass the enzymatic hydrolysis and
      conversion steps preceding the glycolytic pathway. The role played by rumen
      microbiota in the expression of these effects was explored by testing three
      inocula grown on feeds supplying a microflora adapted to fibre, slowly degradable
      or readily degradable starch as the dominant dietary polysaccharide. Data were
      fitted to 2nd-order polynomial models. In fibre-adapted cultures, the yields of
      major VFA were mainly influenced by pH and H2 partial pressure, in opposite ways.
      In wheat grain-adapted cultures, the VFA yields underwent the opposite influences
      of pH, in a curvilinear way for propionate, and Eh since acetate production yield
      was not significantly modified by any factor. In maize grain-adapted cultures,
      acetate production yield was not modified by any factor but H2 in a quadratic way
      when the production yields of higher VFA underwent opposite influences of pH and
      Eh. In conclusion, the effects of environmental factors were dependent on the
      nature of the inoculum, a major source of variation, and more particularly on its
      adaptation to high- or low-fibre diets. These effects were loosely interrelated,
      the pH being the most active factor before the Eh and H2 partial pressure. 

PMID- 24679595
TI  - Food insecurity in French patients with diabetes.

PMID- 24679596
TI  - Fetal blood grouping using cell free DNA - an improved service for RhD negative
      pregnant women.
AB  - Red cell alloimmunisation involves the transplacental movement of maternally
      derived red cell antibodies into the fetal circulation, causing red cell
      haemolysis, fetal anaemia and ultimately fetal death. Current standard UK
      practice is to prevent sensitisation to the D antigen by administering anti-D at
      about 28 weeks' gestation to all RhD negative pregnancies. The determination of
      fetal blood group by non-invasive cell free fetal DNA testing offers an improved
      and more efficient service to RhD negative pregnant women and avoids the
      potential iatrogenic harm associated with standard practice. It also has
      significantly improved the management of women with red cell alloimunisation to D
      and other antigens. This review summarises the past and future management of red
      cell alloimmunisation during pregnancy and the impact of ffDNA tests.

PMID- 24679597
TI  - Implementation of a mandatory donor RHD screening in Switzerland.
AB  - Starting in 2013, blood donors must be tested at least using: (1) one monoclonal
      anti-D and one anti-CDE (alternatively full RhCcEe phenotyping), and (2) all RhD
      negative donors must be tested for RHD exons 5 and 10 plus one further exonic, or
      intronic RHD specificity, according to the guidelines of the Blood Transfusion
      Service of the Swiss Red Cross (BTS SRC). In 2012 an adequate stock of RHD
      screened donors was built. Of all 25,370 RhD negative Swiss donors tested in
      2012, 20,015 tested at BTS Berne and 5355 at BTS Zurich, showed 120 (0.47%) RHD
      positivity. Thirty-seven (0.15%) had to be redefined as RhD positive. Routine
      molecular RHD screening is reliable, rapid and cost-effective and provides safer
      RBC units in Switzerland. 

PMID- 24679598
TI  - Diagnostic tests often fail to lead to changes in patient outcomes.
AB  - OBJECTIVES: To evaluate the effects of diagnostic testing on patient outcomes in
      a large sample of diagnostic randomized controlled trials (D-RCTs) and to examine
      whether the effects for patient outcomes correlate with the effects on management
      and with diagnostic accuracy. STUDY DESIGN AND SETTING: We considered D-RCTs that
      evaluated diagnostic interventions for any condition and reported effectiveness
      data on one or more patient outcomes. We calculated odds ratios for patient
      outcomes and outcomes pertaining to the use of further diagnostic and therapeutic
      interventions and the diagnostic odds ratio (DOR) for the accuracy of
      experimental tests. RESULTS: One hundred forty trials (153 comparisons) were
      eligible. Patient outcomes were significantly improved in 28 comparisons (18%).
      There was no concordance in significance and direction of effects between the
      patient outcome and outcomes for use of further diagnostic or therapeutic
      interventions (weighted kappa 0.02 and 0.09, respectively). The effect size for
      the patient outcome did not correlate with the effect sizes for use of further
      diagnostic (r = 0.05; P = 0.78) or therapeutic interventions (r = 0.18; P = 0.08)
      or the experimental intervention DOR in the same trial (r = -0.24; P = 0.51).
      CONCLUSION: Few tests have well-documented benefits on patient outcomes.
      Diagnostic performance or the effects on management decisions are not necessarily
      indicative of patient benefits.

PMID- 24679599
TI  - [Home care of premature rupture of membranes prior to 37 weeks' gestation].
AB  - OBJECTIVE: To compare maternal and perinatal outcome according to gestational age
      at delivery and length of latency period in a group of patients with preterm
      premature rupture of membranes. To propose and evaluate an antenatal protocol of
      home care in a selected group of them. PATIENTS AND METHODS: Inclusion criteria
      was a delivery in our maternity related to a rupture of membranes prior to 37
      week's gestation. Expectant management was applied. Home care management was
      proposed for patients hospitalised at least 5 days and meeting strict criteria.
      Maternal-fetal clinical monitoring was performed daily and biological and
      ultrasound monitoring weekly until 37 or 38 week's gestation. RESULTS: We
      included 222 patients. There was a significant increase in perinatal
      complications for neonates before 36 week's gestation. Maternal and perinatal
      outcomes were not influenced by the latency period. In the overall patients, 44
      were hospitalised at least 5 days and 9 could return at home. It seems that there
      was no difference concerning maternal and fetal complications between home care
      and hospitalized patients. DISCUSSION AND CONCLUSION: In preterm premature
      rupture of membranes after 34 week's gestation, monitored expectant management
      can reduce prematurity complications without increasing infectious complications.
      After an initial hospitalization, for a small proportion of them, home care seems
      possible without increasing maternal and fetal morbidity.

PMID- 24679600
TI  - [Anonymous sperm donation does not increase the risk for unions between relatives
      nor the incidence of autosomal recessive diseases due to consanguinity].

PMID- 24679601
TI  - [Conservation of the nipple-areola complex in case of mastectomy].
AB  - Nipple-Sparing Mastectomy (NSM) is a procedure with skin-sparing mastectomy and
      nipple-areolar complex preservation in association with immediate reconstruction.
      The aim of this publication is to perform a review of oncological results,
      technical procedure, complications and indications of NSM with discussion of post
      mastectomy radiotherapy indication. Local areolar recurrence is rare and
      treatment is performed by resection of the nipple-areolar complex. The nipple
      areolar complex necrosis rate is a specific complication, observed between 1 to
      30% in literature studies. Incisions and surgical procedure of dissection are
      discussed. 

PMID- 24679602
TI  - [Adverse pregnancy outcomes after Assisted Reproduction Technology in women with
      endometriosis].
AB  - OBJECTIVE: While association between endometriosis and infertility is well
      established, there are few studies about the impact of endometriosis on adverse
      pregnancy outcomes. The aim of this study was to determine the effect of
      endometriosis on obstetric outcomes and whether the severity of the disease had
      an influence on these. PATIENTS AND METHODS: We performed a retrospective study
      to investigate the obstetric outcomes of a population of 1204 subfertile women,
      including 258 with endometriosis, who obtained, thanks to assisted reproduction
      technology, a singleton pregnancy evolving beyond embryonic stage. Two analyzes
      were performed. The first compared women with endometriosis to women with other
      causes of infertility. The second observed adverse pregnancy outcomes according
      to AFS-R stages of endometriosis. RESULTS: The overall rate of live birth
      children was 95.8%. In case of endometriosis, there was a significant increase of
      the incidence of preterm delivery, especially before 32 weeks amenorrhea (6.2% vs
      3.1% in the group "without endometriosis", P = 0.03), antenatal bleeding (5.3% vs
      2.2%, P = 0.01) and placenta previa (4.9% vs 0.9%, P < 0.0001). The incidence of
      gestational diabetes was significantly decreased (0.4% vs 2.7%, P = 0.04). There
      was no correlation between endometriosis and cesarean section or preeclampsia, or
      between the AFS-R stage and adverse pregnancy outcomes. DISCUSSION AND
      CONCLUSION: Endometriosis is a factor of obstetrical risk, independently of the
      infertility it causes. The AFS-R score does not seem to be representative of
      obstetric outcomes beyond first trimester of pregnancy for women with
      endometriosis.

PMID- 24679603
TI  - Hippocampus-specific deficiency in RNA editing of GluA2 in Alzheimer's disease.
AB  - Adenosine to inosine (A-to-I) RNA editing is a base recoding process within
      precursor messenger RNA, catalyzed by members of the adenosine deaminase acting
      on RNA (ADAR) family. A notable example occurs at the Q/R site of the alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor subunit GluA2.
      Abnormally, low editing at this site leads to excessive calcium influx and cell
      death. We studied hippocampus and caudate samples from Alzheimer's disease (AD)
      patients and age-matched healthy controls, using direct sequencing and a high
      accuracy primer-extension technique to assess RNA editing at the Q/R GluA2 site.
      Both techniques revealed lower, more variable RNA editing in AD, specific to the
      hippocampus and the GluA2 site. Deficient editing also characterized the
      hippocampus of apolipoprotein epsilon4 allele carriers, regardless of clinical
      diagnosis. In AD, messenger RNA expression of neuronal markers was decreased in
      the hippocampus, and expression of the Q/R-site editing enzyme ADAR2 was
      decreased in caudate. These findings provide a link between neurodegenerative
      processes and deficient RNA editing of the GluA2 Q/R site, and may contribute to
      both diagnosis and treatment of AD. 

PMID- 24679605
TI  - WITHDRAWN: MiR-200 family and cancer: Function, regulation and signaling.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24679604
TI  - Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain.
AB  - Epigenetic processes play a key role in the central nervous system and altered
      levels of 5-methylcytosine have been associated with a number of neurologic
      phenotypes, including Alzheimer's disease (AD). Recently, 3 additional cytosine
      modifications have been identified (5-hydroxymethylcytosine, 5-formylcytosine,
      and 5-carboxylcytosine), which are thought to be intermediate steps in the
      demethylation of 5-methylcytosine to unmodified cytosine. Little is known about
      the frequency of these modifications in the human brain during health or disease.
      In this study, we used immunofluorescence to confirm the presence of each
      modification in human brain and investigate their cross-tissue abundance in AD
      patients and elderly control samples. We identify a significant AD-associated
      decrease in global 5-hydroxymethylcytosine in entorhinal cortex and cerebellum,
      and differences in 5-formylcytosine levels between brain regions. Our study
      further implicates a role for epigenetic alterations in AD. 

PMID- 24679606
TI  - Progressive dysautonomia in two patients with xeroderma pigmentosum group A.
AB  - BACKGROUND: Xeroderma pigmentosum group A (XPA) is a rare autosomal-recessive
      disorder caused by a defect in nucleotide excision repair. Progressive
      dysautonomia in patients with XPA is rarely described. PATIENTS: Two juvenile
      male patients with XPA suffered from dysphagia, sleep interruption, and dysuria
      from the age of 10 to 19 years, successively. These autonomic symptoms might have
      been caused by progressive descending degeneration of cranial nerves IX and X and
      the sacral parasympathetic nerve, including Onuf's nucleus. One patient died from
      sudden cardiopulmonary arrest during postural change and tracheal suction.
      RESULTS: Heart rate variability analyses of these patients revealed
      parasympathetic dysautonomia, based on decreased high-frequency values.
      CONCLUSIONS: The insidiously progressive dysautonomia in these two patients with
      XPA suggested progressive descending degeneration extending from the medulla
      oblongata to the sacral spinal cord, which is an ominous sign of end-stage
      disease and a risk factor of sudden death attributable to XPA.

PMID- 24679607
TI  - Health-related quality of life in children and adolescents with spinal muscular
      atrophy in the Czech Republic.
AB  - BACKGROUND: Spinal muscular atrophy is a rare hereditary neuromuscular disorder
      (with a prevalence of 1 per 30,000) that greatly debilitates patients and, in
      most cases, shortens their life expectancy. Although there is no causal therapy,
      improvements in symptomatic therapy have extended patients' life expectancy and
      increased their quality of life. Unfortunately, the advancements in care vary
      from country to country. To improve the care for children with spinal muscular
      atrophy in the Czech Republic, we created a survey to obtain the baseline
      information about their quality of life and compared the data with equivalent
      data from the United States. METHODS: We used the Pediatric Quality of Life
      Inventory 3.0 Neuromuscular Measurement Model, which is a health-related quality
      of life questionnaire specific to children with neuromuscular disorders. The
      survey was conducted on 35 children with genetically proven spinal muscular
      atrophy and their parents. RESULTS: Compared with the US data, the Czech data
      generally show a lower quality of life, mainly in the family resources part. The
      greatest score was achieved in the section about communication. Altogether, the
      parents' scores are lower than those of the children. CONCLUSION: In the Czech
      Republic, patients with spinal muscular atrophy and, especially their parents,
      have a significantly lower quality of life compared with US patients, mostly
      because of economic factors and a lack of social support. Our results reveal
      areas toward which improvement should be directed. The need for family support
      through social care as well as civic, patient, or organizational support is
      accentuated.

PMID- 24679608
TI  - Not just cerebral palsy: diastrophic dysplasia presenting as spastic
      quadriparesis.

PMID- 24679609
TI  - Screening for obstructive sleep apnea in children with Down syndrome.
AB  - OBJECTIVE: To compare symptoms of obstructive sleep apnea (OSA) and
      polysomnography (PSG) results in children with Down syndrome and typically
      developing children. STUDY DESIGN: A total of 49 children with Down syndrome
      referred for PSG between 2008 and 2012 were matched with typically developing
      children of the same sex, age, and OSA severity who had undergone PSG in the same
      year. A parent completed a sleep symptom questionnaire for each child. Sleep
      quality and measures of gas exchange were compared between the matched groups.
      RESULTS: The 98 children (46 females, 52 males) had mean age of 6.2 years (range,
      0.3-16.9 years). Fourteen children had primary snoring, and 34 had OSA (9 mild, 7
      moderate, and 19 severe). Children with Down syndrome had more severe OSA
      compared with 278 typically developing children referred in 2012. Symptom scores
      were not different between the matched groups. Those with Down syndrome had a
      higher average pCO2 during sleep (P = .03) and worse McGill oximetry scores.
      CONCLUSION: Compared with closely matched typically developing children with OSA
      of comparable severity, children with Down syndrome had a similar symptom profile
      and slightly worse gas exchange. Referred children with Down syndrome had more
      severe OSA than referred typically developing children, suggesting a relative
      reluctance by parents or doctors to investigate symptoms of OSA in children with
      Down syndrome. These findings highlight the need for formal screening tools for
      OSA in children with Down syndrome to improve detection of the condition in this
      high-risk group.

PMID- 24679610
TI  - Glucose-6-phosphate dehydrogenase activity levels in white newborn infants.
AB  - OBJECTIVE: To define normal levels of glucose-6-phosphate dehydrogenase (G6PD)
      activity in a population of North American white newborns. STUDY DESIGN: We
      studied 2 white newborn populations, >=35 weeks of gestation. In the
      retrospective study, G6PD activity was measured (on clinical indication) in 242
      newborns aged <=7 days. In the prospective study, we measured G6PD activity in
      umbilical cord blood samples in 347 newborns and daily transcutaneous bilirubin
      levels in these infants. RESULTS: The mean G6PD activity level was 12.3 +/- 3.1
      units per gram hemoglobin (U/gHb) in the retrospective population and 13.3 +/-
      1.8 U/gHb in the prospective population, and there was no difference between
      males and females. The distribution of values suggested that infants with
      activity levels <7 U/gHb should be considered deficient and 8 infants (6 males
      and 2 females), all in the retrospective population had such levels. CONCLUSIONS:
      As in other ethnic populations, the mean G6PD activity in white newborn infants
      is substantially greater than that of white adults. The lower limits of normal
      are also similar to those of other newborn ethnic groups and of adults. The
      diagnosis of G6PD deficiency should be considered in any white infant whose G6PD
      activity is <7 U/gHb.

PMID- 24679611
TI  - Prevalence and characteristics of e-cigarette users in Great Britain: Findings
      from a general population survey of smokers.
AB  - BACKGROUND: E-cigarettes may be effective smoking cessation aids and their use by
      smokers has been growing rapidly. It is important to observe and assess natural
      patterns in the use of e-cigarettes whilst experimental data accumulates. This
      paper reports the prevalence of e-cigarette awareness, beliefs and usage,
      including brand choice, and characterises the socio-demographic and smoking
      profile associated with current use, among the general population of smokers and
      recent ex-smokers. METHODS: Data were obtained from 3538 current and 579 recent
      ex-smokers in a cross-sectional online survey of a national sample of smokers in
      Great Britain in November and December 2012. Differences between current and
      recent ex-smokers in the prevalence of e-cigarette awareness, beliefs and usage
      were examined and the socio-demographic and smoking profile associated with
      current use of e-cigarettes was assessed in a series of simple and multiple
      logistic regressions. RESULTS: Ninety-three percent of current and recent ex
      smokers (n=3841) were aware of e-cigarettes. Approximately a fifth (n=884) were
      currently using e-cigarettes, whilst just over a third (n=1507) had ever used
      them. Sixty-seven percent of the sample (n=2758) believed e-cigarettes to be less
      harmful than cigarettes; however, almost a quarter (n=994) remained unsure. Among
      both current and recent ex-smokers, the most popular reasons for using were
      health, cutting down and quitting (each >80%) and 38% used the brand 'E-lites'.
      Among current smokers who were aware of but had never used e-cigarettes,
      approximately half (n=1040) were interested in using them in the future. Among
      current smokers, their use was associated with higher socio-economic status
      (OR=1.48, 95%CI=1.25-1.75), smoking more cigarettes (OR=1.02, 95%CI=1.01-1.03)
      and having a past-year quit attempt (OR=2.82, 95%CI=2.38-3.34). CONCLUSIONS:
      There is a near universal awareness of e-cigarettes and their use appears to be
      common among smokers in Great Britain although a quarter of all smokers are
      unsure as to whether e-cigarettes are less harmful than cigarettes. E-lites - a
      brand that delivers a low dose of nicotine - is the most popular. E-cigarette
      users appear to have higher socio-economic status, to smoke more cigarettes per
      day and to have attempted to quit in the past year.

PMID- 24679613
TI  - Confirm Vivek Murthy for US Surgeon General.

PMID- 24679612
TI  - Compulsive use of Internet-based sexually explicit media: Adaptation and
      validation of the Compulsive Internet Use Scale (CIUS).
AB  - Despite evidence that viewing sexually explicit media (SEM) may contribute to
      greater numbers of sexual partners, sexual risk taking, greater interest in group
      sex, and lower self-esteem among men who have sex with men (MSM), research has
      not addressed compulsive use of Internet-based SEM due to the lack of a validated
      measure for this population. This report investigates the psychometric properties
      of the 14-item Compulsive Internet Use Scale (CIUS; Meerkerk, van den Eijnden,
      Vermulst, & Garretsen, 2009) adapted to assess the severity of compulsive
      Internet SEM use. A total of 265 Internet SEM-viewing MSM participated in an
      online survey about their SEM preferences, viewing habits, and recent sexual
      behaviors. A principal components analysis revealed a single-component, 13-item
      scale to adequately assess the cognitive, emotional, and behavioral aspects of
      this phenomenon, with a high internal consistency (alpha=.92). Greater compulsive
      use of Internet SEM was positively correlated with several relevant variables
      including boredom, sexual frustration, time spent viewing Internet SEM, and
      number of recent male sexual partners. The results offer preliminary evidence for
      the reliability and validity of using an adapted version of the CIUS to
      understand compulsive Internet SEM use, and allow for more research into the
      potential negative consequences of compulsive SEM use.

PMID- 24679614
TI  - Towards a better life with Alzheimer's disease.

PMID- 24679615
TI  - Arts for health's sake.

PMID- 24679616
TI  - Health inequalities and France's national health strategy.

PMID- 24679619
TI  - Philip Cotton: building a medical college in Rwanda.

PMID- 24679620
TI  - Research: increasing value, reducing waste.

PMID- 24679621
TI  - Research: increasing value, reducing waste.

PMID- 24679622
TI  - Research: increasing value, reducing waste.

PMID- 24679623
TI  - Research: increasing value, reducing waste.

PMID- 24679624
TI  - Research: increasing value, reducing waste.

PMID- 24679625
TI  - Research: increasing value, reducing waste.

PMID- 24679626
TI  - Research: increasing value, reducing waste.

PMID- 24679627
TI  - Research: increasing value, reducing waste - Authors' reply.

PMID- 24679628
TI  - Robespierre: the oldest case of sarcoidosis?

PMID- 24679629
TI  - Robespierre: the oldest case of sarcoidosis?

PMID- 24679630
TI  - Robespierre: the oldest case of sarcoidosis? - Authors' reply.

PMID- 24679631
TI  - Salt reduction strategies in China.

PMID- 24679632
TI  - Giant cell arteritis.

PMID- 24679633
TI  - Rituximab with or without bevacizumab for the treatment of patients with relapsed
      follicular lymphoma.
AB  - INTRODUCTION/BACKGROUND: Inhibition of tumor angiogenesis by the interruption of
      VEGF pathway signaling is of therapeutic value in several solid tumors.
      Preclinical evidence supports similar importance of the pathway in non-Hodgkin
      lymphoma. In this randomized phase II trial, we compared the efficacy and
      toxicity of rituximab with bevacizumab versus single-agent rituximab, in patients
      with previously-treated follicular lymphoma. PATIENTS AND METHODS: Patients (n =
      60) were randomized (1:1) to receive rituximab (375 mg/m(2) intravenously [I.V.]
      weekly for 4 weeks) either as a single agent or with bevacizumab (10 mg/kg I.V.
      on days 3 and 15). Patients with an objective response or stable disease at week
      12 received 4 additional doses of rituximab (at months 3, 5, 7, and 9); patients
      who received rituximab/bevacizumab also received bevacizumab 10 mg/kg I.V. every
      2 weeks for 16 doses. RESULTS: After a median follow-up of 34 months, PFS was
      improved in patients who received rituximab/bevacizumab compared with patients
      who received rituximab alone (median 20.7 vs. 10.4 months respectively; HR, 0.40
      (95% confidence interval [CI], 0.20-0.80); P = .007). Overall survival was also
      improved numerically (73% vs. 53% at 4 years), but did not reach statistical
      significance (HR, 0.40 (95% CI, 0.15-1.05); P = .055). The addition of
      bevacizumab increased the toxicity of therapy, but both regimens were well
      tolerated (no grade 4 toxicity). CONCLUSION: The addition of bevacizumab to
      rituximab significantly improved PFS. The role of angiogenesis inhibition in the
      treatment of follicular lymphoma requires further definition in larger clinical
      trials.

PMID- 24679635
TI  - 2013 ASMBS Presidential address 30 years of accomplishments: where do we go from
      here?

PMID- 24679636
TI  - Accreditation in metabolic and bariatric surgery: pro versus con.

PMID- 24679634
TI  - HIV pre-exposure prophylaxis for people who inject drugs: a review of current
      results and an agenda for future research.
AB  - INTRODUCTION: Studies examining the use of pre-exposure prophylaxis (PrEP) to
      prevent HIV transmission among people who inject drugs (PWIDs) have not been
      adequately summarized. Recently, the Bangkok Tenofovir Study has shown that PrEP
      may be effective at reducing new HIV infections among this high-risk group. This
      randomized controlled trial was the first study to specifically examine the
      efficacy of PrEP among PWIDs. In this review, we present the current state of
      evidence regarding the use of PrEP to prevent HIV infection in PWID populations,
      and set an agenda for future research to inform the most effective implementation
      of PrEP in the context of existing evidence-based HIV prevention strategies.
      DISCUSSION: Despite positive trial results confirming that PrEP may prevent HIV
      transmission among PWIDs, there remain many questions regarding the
      interpretation of these results, as well as obstacles to the implementation of
      PrEP regimens within highly diverse drug-using communities. Aside from the
      Bangkok Tenofovir Study, we identified only one other published study that has
      collected empirical data to inform the use of PrEP among PWIDs. The large gap in
      research regarding the use and implementation of PrEP for PWIDs signals the need
      for further research and attention. CONCLUSIONS: We recommend that future
      research efforts focus on elucidating the generalizability of the Bangkok
      Tenofovir Study results in other injection drug-using populations, examining the
      willingness of PWIDs to use PrEP in diverse contexts, identifying barriers to
      adherence to PrEP regimens and determining the most effective ways to implement
      PrEP programmes within the context of existing evidence-based prevention
      strategies, including opioid substitution therapy and needle and syringe
      distribution programmes.

PMID- 24679637
TI  - Comment on: Body mass index and diabetes status do not affect postoperative
      infection rates after bariatric surgery.

PMID- 24679638
TI  - Geographic obesity burden and Internet searches for bariatric surgery: importance
      of a combined search strategy.

PMID- 24679639
TI  - Stakeholder involvement is essential for patient centered applications of Google
      Trends research.

PMID- 24679641
TI  - [Gastric outlet obstruction in a patient with percutaneous gastrostomy].

PMID- 24679642
TI  - [Successful eradication of genotype 4 HCV with telaprevir-based triple antiviral
      therapy].

PMID- 24679643
TI  - Thromboelastographic phenotypes of fibrinogen and its variants: clinical and non
      clinical implications.
AB  - INTRODUCTION: Thromboelastography (TEG), a widely used clinical point of care
      coagulation test, is poorly understood. To investigate its fibrin determinants we
      used normal and variant fibrinogen isolates. MATERIALS AND METHODS: We focused
      mainly on the TEG maximum signal amplitude (MA), a shear modulus and clot
      stiffness indicator. Isolates included normal des-alphaC, cord, and abnormal
      congenital variants with amino acid substitutions or deletions that impaired
      fibrin polymerization. Heterophenotypic congenital isolates were from
      cryoprecipitate-depleted plasma owing to their more diminished clot MA than their
      cryoprecipitate counterparts. By colorimetric assay, the amount of fibrinogen
      adsorbed by untreated TEG cups was 83.5+/-12.4 pM/cm(2), n=18. Thrombin-induced
      clots were obtained at pH6.4 or 7.4, the latter containing 8mM CaCl2, and 14%
      afibrinogenemic plasma with and without gel-sieved platelets. RESULTS AND
      CONCLUSIONS: Measured by the water droplet contact angle, >90% reduction of
      surface hydrophobicity by exposure of TEG cup and pin to ozone plasma decreased
      MA by 74%. Increasing normal fibrinogen or thrombin concentrations progressively
      increased MA. Platelets increased MA further ~2 fold, except for >=10 fold for
      des-alphaC clots. Examined in the absence of platelets, MA of heterophenotypic
      fibrin variants averaged 21%, n=15. The results imply that essential MA
      determinants include hydrophobic fibrinogen/fibrin adsorption and each
      polymerization contact site, with substantial enhancement by platelets. Also,
      cryoprecipitate-harvested soluble fibrinogen/fibrin complexes contained mostly
      normal molecules, while cryoprecipitate-depleted plasma contained mostly variant
      molecules. Moreover, significantly decreased MA by fibrinogen anomalies and/or
      low level thrombin generation can potentially impact clinical interpretation of
      MA.

PMID- 24679644
TI  - Consumer characteristics and perceptions of chiropractic and chiropractic
      services in Australia: results from a cross-sectional survey.
AB  - OBJECTIVE: The purpose of this study was to describe patient characteristics and
      summarize their perceptions of chiropractic in Australia. METHODS: This study is
      part of a broader study aiming to extend the knowledge of the role of
      chiropractic within the current health care environment. A 33-item, paper-based,
      cross-sectional survey of a sample of patients from 100 systematically sampled
      chiropractic clinics from all the states and territories of Australia was
      conducted. The survey focused on patient demographics, socioeconomic status,
      perceived health status, and perceptions of chiropractic and chiropractic
      services. RESULTS: A total of 486 responses were received (24.3% response rate).
      Respondents were predominantly female patients (67.1%) of the 45- to 64-year age
      group. Approximately half of the respondents reported a pretax annual income
      exceeding $40000. Most patients sought chiropractic services because of
      musculoskeletal disorders (68.7%) and for general health (21.2%), and personal
      beliefs motivated most respondents (70.2%) to visit a chiropractor. Most
      respondents would seek the chiropractic services again (97.5%) and were satisfied
      with the service received. CONCLUSIONS: The results of this study show that the
      typical chiropractic patient in Australia is a middle-aged woman with a moderate
      to high income. Although only a small proportion of the Australian population
      sees a chiropractor, this group seems to be satisfied with the service.

PMID- 24679645
TI  - Coarctation of the aorta can no longer be considered a benign condition.

PMID- 24679646
TI  - Reprint of: Effects of the antidepressant venlafaxine on fish brain serotonin and
      predation behavior.
AB  - Antidepressants that enter receiving waters through final treated wastewater
      effluent have exhibited relatively low acute toxicity in traditional fish tests
      at currently measured concentrations. However, the psychotropic mode of action of
      these compounds warrants examination of the behavioral effects these chemicals
      may have on aquatic organisms. Previous research has demonstrated that exposure
      to the antidepressant fluoxetine causes decreased brain serotonin levels in fish
      and results in a decreased ability to capture prey. Another antidepressant,
      venlafaxine, has been found at low MUg/L concentrations in final treated
      wastewater effluent. The objective of this study was to quantify the effects of
      venlafaxine on fish predation behavior and determine if this effect was
      correlated with changes in brain neurotransmitter concentrations. The predator
      prey bioassay used hybrid striped bass (Morone saxatilis x Morone chrysops) as
      the predator and fathead minnows (Pimephales promelas) as prey. Bass were exposed
      to venlafaxine (0-500 MUg/L) for a period of 6 days and then allowed to recover
      for 6 days. During both exposure and recovery, bass were fed four minnows every
      third day. The time to capture the minnows was quantified and compared among
      treatments to determine if there was an effect on predation behavior. Brain
      tissue was analyzed for serotonin, norepinephrine, and dopamine, to determine the
      relationship between exposure concentration, brain monoamine levels, and
      predation behavior. Results indicated that venlafaxine exposures increased time
      to capture prey 1 and 2 by day 6 for the 250 and 500 MUg/L treatments. Time to
      capture prey 3 was increased for all venlafaxine treatments by day 6. Venlafaxine
      caused a statistically significant decrease in brain serotonin concentrations
      that initially decreased in a dose dependent manner before reaching a steady
      state by the end of exposures for all treatments. No significant, dose-dependent
      changes in dopamine or norepinephrine were seen. Brain serotonin alone did not
      adequately explain behavioral results. Serotonin response in other tissues as
      well as peripheral effects may have accounted for additional behavioral responses
      after brain serotonin reached a depressed steady state.

PMID- 24679647
TI  - The role of unconditional cash transfers during a nutritional emergency in Maradi
      region, Niger: a pre-post intervention observational study.
AB  - OBJECTIVE: To assess the effect of an unconditional cash transfer (CT)
      implemented as part of an emergency response to food insecurity during a declared
      state of emergency. DESIGN: Pre-post intervention observational study involving
      two rounds of data collection, i.e. baseline (April 2012) and final survey
      (September 2012), on the same cohort of 'poor' and 'very poor' households
      enrolled by Save the Children in an unconditional CT programme. SETTING: Aguie
      district, Maradi, Niger. SUBJECTS: Households with a non-acutely malnourished
      child aged 6-36 months (n 412). RESULTS: The study showed that the living
      standards of 'poor' and 'very poor' households improved, as indicated by a
      reduction in poverty-related indicators and an improvement in household food
      security. Anthropometric outcomes for children aged 6-36 months improved
      significantly, despite a decline in child health and women's well-being and
      autonomy. Risk factors for becoming acutely malnourished post-intervention were
      being from a very poor household at baseline, starting the lean season with low
      weight-for-height Z-score (WHZ <-1) and the presence of co-morbidity.
      CONCLUSIONS: The results of the study are consistent with the published evidence
      regarding the general impact of CT and suggest it is plausible that giving cash
      during an emergency can help safeguard living standards of the very poor and
      poor. While improvements in childhood nutrition status were seen it is not
      possible to attribute these to the CT programme. However, knowledge of the risk
      factors for acute malnutrition in a particular setting can be used to influence
      the design of future CT interventions for which a controlled trial would be
      recommended if feasible.

PMID- 24679648
TI  - Aneurysmal acute subdural hemorrhage: prognostic factors associated with
      treatment.
AB  - Acute subdural hematoma is an uncommon presentation of aneurysmal hemorrhage that
      has been identified as a poor prognostic sign. Current series are small, have
      short follow-up, or were collected over a long period during which treatment
      evolved. To evaluate prognostic factors, we analyzed a large modern series of
      aneurysmal subdural hematoma (aSDH) with long-term follow-up. A prospectively
      maintained database was queried for patients presenting with aSDH from 2001-2013.
      Thirty patients met the study criteria. Statistical analysis was performed with
      unpaired t-test or Fisher's exact test. Aneurysm treatment involved open clipping
      (n=18), endosaccular coiling (n=8), both (n=1), or no treatment (n=3). Good
      Glasgow Outcome Scale score at discharge was present in 20% and increased to 40%
      at 6-12 months postoperatively. Good clinical presentation was associated with
      good final outcome in 75%, whereas poor clinical presentation correlated with
      good outcome in 30%. Good outcome correlated with younger age (p=0.04), smaller
      aneurysm (p=0.04), and lower Hunt-Hess score (HH) at intervention (p=0.04).
      Favorable outcome did not correlate with sex, race, presence of subarachnoid or
      intraparenchymal hemorrhage, size or laterality of hemorrhage, midline shift,
      aneurysm treatment modality, or HH at admission (p>0.15). There was no difference
      between good and poor outcomes in terms of time to treatment or hematoma
      evacuation. Poor clinical presentation may be exaggerated by mass effect of
      hematoma; aggressive treatment is not futile. Presenting neurological status,
      age, and aneurysm size are predictors of outcome, while laterality and size of
      hematoma and extent of midline shift are not, suggesting that clinical status is
      more important than radiographic findings.

PMID- 24679649
TI  - Visceral organ weights, digestion and carcass characteristics of beef bulls
      differing in residual feed intake offered a high concentrate diet.
AB  - This study examined the relationship of residual feed intake (RFI) with
      digestion, body composition, carcass traits and visceral organ weights in beef
      bulls offered a high concentrate diet. Individual dry matter (DM) intake (DMI)
      and growth were measured in a total of 67 Simmental bulls (mean initial BW 431 kg
      (s.d.=63.7)) over 3 years. Bulls were offered concentrates (860 g/kg rolled
      barley, 60 g/kg soya bean meal, 60 g/kg molasses and 20 g/kg minerals per
      vitamins) ad libitum plus 0.8 kg grass silage DM daily for 105 days pre
      slaughter. Ultrasonic muscle and fat depth, body condition score (BCS),
      muscularity score, skeletal measurements, blood metabolites, rumen fermentation
      and total tract digestibility (indigestible marker) were determined. After
      slaughter, carcasses and perinephric and retroperitoneal fat were weighed,
      carcasses were graded for conformation and fat score and weight of non-carcass
      organs, liver, heart, kidneys, lungs, gall bladder, spleen, reticulo-rumen full
      and empty and intestines full, were determined. The residuals of the regression
      of DMI on average daily gain (ADG), mid-test metabolic BW (BW0.75) and the fixed
      effect of year, using all animals, were used to compute individual RFI
      coefficients. Animals were ranked on RFI and assigned to high (inefficient),
      medium or low groupings. Overall mean ADG and daily DMI were 1.6 kg (s.d.=0.36)
      and 9.4 kg (s.d.=1.16), respectively. High RFI bulls consumed 7 and 14% more DM
      than medium and low RFI bulls, respectively (P<0.001). No differences between
      high and low RFI bulls were detected (P>0.05) for ADG, BW, BCS, skeletal
      measurements, muscularity scores, ultrasonic measurements, carcass weight,
      perinephric and retroperitoneal fat weight, kill-out proportion and carcass
      conformation and fat score. However, regression analysis indicated that a 1 kg
      DM/day increase in RFI was associated with a decrease in kill-out proportion of
      20 g/kg (P<0.05) and a decrease in carcass conformation of 0.74 units (P<0.05).
      Weight of non-carcass organs did not differ (P>0.05) between RFI groups except
      for the empty weight of reticulo-rumen, which was 8% lighter (P=0.05) in low RFI
      compared with high RFI bulls. Regression analysis indicated that a 1 kg DM/day
      increase in RFI was associated with a 1 kg increase in reticulo-rumen empty
      weight (P<0.05). Of the visceral organs measured, the reticulo-rumen may be a
      biologically significant contributory factor to variation in RFI in beef bulls
      finished on a high concentrate diet. 

PMID- 24679650
TI  - [Safety and efficacy of whole breast irradiation with a concomitant boost:
      analysis of 121 cases treated at the Institute of Cancerology of Lorraine].
AB  - PURPOSE: To evaluate the safety and efficacy of whole breast irradiation with a
      concomitant boost. PATIENTS AND MATERIALS: This is a retrospective study of 121
      patients with node negative T1-T2 breast tumors inferior to 3 cm in diameter,
      previously treated by conservative surgery without chemotherapy. A dose of 50 Gy
      was delivered to the whole breast in 2 Gy daily fractions with 5 weekly
      treatments. A concomitant boost to the lumpectomy site delivered a total of 10 Gy
      in 1 Gy fractions twice a week. This would result in an equivalent tumour bed
      dose (assuming an alpha/beta of 4) of approximately 65 Gy in 2 Gy fractions.
      RESULTS: Over 7 years, 121 patients were treated. The median age was 67 years
      (range, 46-86 years). Stage distribution was: 115 T1, 6 T2; 116 tumors had
      positive hormonal receptors, 6 grade SBR3. With a median follow-up of 6 years
      (range, 1.4-11.4 years), 5-year overall survival was 98.2% (95% confidence
      interval [CI] 0.95-1), disease-free survival was 100% and local recurrence-free
      survival 100%. The maximum acute skin toxicity by the end of treatment was grade
      2. Cosmetic outcomes were good on the long term. One spontaneous rib fracture was
      observed 1 year after radiotherapy among 76 patients. CONCLUSIONS: The study
      shows that whole breast radiation therapy with a concomitant boost is safe and
      effective for selected patients with low risk of relapse, and gives excellent
      long term results. This protocol represents a good alternative to longer standard
      whole breast radiation therapy with sequential boost to the lumpectomy bed.

PMID- 24679651
TI  - Thyroid lymphoma on a background of Hashimoto's thyroiditis: PET/CT appearances.
AB  - Primary thyroid lymphoma is a rare thyroid tumor accounting for only 5% of all
      thyroid malignancies. It is more common in patients with a background history of
      chronic thyroiditis. PET/CT is helpful in the initial staging and for follow up
      to assess treatment response. 

PMID- 24679652
TI  - Hepatic fat accumulation with sparing associated with portal vein duplication.
AB  - Duplication of the portal vein is a rare congenital anomaly. We experienced a
      case of duplication of the portal vein associated with hepatic fat accumulation
      with sparing. Fat accumulation was seen in the central portion of the liver,
      which was supplied by the portal vein coursing upward to the porta hepatis
      (Portal Vein 2), and sparing of fatty liver was seen in the peripheral portion of
      the liver, which was supplied by the portal vein entering the liver inferiorly
      (Portal Vein 1). 

PMID- 24679653
TI  - Cefepime monotherapy for febrile neutropenia in patients with lung cancer.
AB  - We assessed the efficacy and safety of cefepime monotherapy (1 g intravenously
      every 8 h) for febrile neutropenia in patients with lung cancer in a multi
      institutional phase II study. Patients treated with chemotherapy with or without
      radiotherapy for lung cancer were eligible for this study. Other eligibility
      criteria included fever (temperature of >=38.0  degrees C) and an absolute
      neutrophil count of <500/mm(3) or <1000/mm(3) with an expected decline to
      <500/mm(3) within the next 48 h. Risk assessment was performed using the
      Multinational Association of Supportive Care in Cancer risk-index score. Cefepime
      1 g was given intravenously every 8 h. The primary endpoint was the response rate
      at the end of cefepime therapy. Co-administration of granulocyte-colony
      stimulating factor was permitted. Of 54 patients enrolled, 39 were classified in
      the low-risk group and 15 in the high-risk group. Overall response rate was 78%
      (95% CI: 64.4-88.0%). The response rates were 85% (95% CI: 69.5-94.1%) in the low
      risk group and 60% (95% CI: 32.3-83.7%) in the high-risk group, respectively. One
      patient died from septic shock due to Enterobacter cloacae bacteremia. There was
      no significant adverse event. Cefepime 1 g intravenously every 8 h appears to be
      effective for febrile neutropenia in patients with lung cancer, especially in
      those with low-risk febrile neutropenia, and is well tolerated. CLINICAL TRIAL
      REGISTRATION: UMIN Clinical Trials Registry, UMIN000006157.

PMID- 24679654
TI  - Recurrence of chronic pulmonary aspergillosis after discontinuation of
      maintenance treatment by antifungal triazoles.
AB  - OBJECTIVE: To assess the prevalence and risk factors of recurrence of chronic
      pulmonary aspergillosis (CPA) after discontinuation of antifungal triazoles.
      METHOD: We reviewed the medical records of CPA patients who achieved resolution
      of clinical and radiographic manifestations and stopped taking antifungal
      triazoles between June 2006 and June 2012 at Tokyo National Hospital. We
      evaluated whether there was CPA recurrence within 1 year after treatment
      cessation and investigated risk factors for relapse. The association of anti
      Aspergillus antibody conversion with CPA recurrence was also reviewed. RESULTS: A
      total of 39 patients were included in this study and there was CPA recurrence in
      14 patients. Compared with the Non-recurrence group, the Recurrence group
      exhibited 1) younger age (p = 0.017), 2) more than one lung lobe affected by CPA
      more frequently (p = 0.008), 3) longer duration needed to remit manifestations of
      chest radiograph (p = 0.031), 4) longer antifungal treatment duration (p =
      0.042). The present study did not reveal an association between negative
      conversion of serum anti-Aspergillus antibody and recurrence risk. Multivariate
      logistic regression analysis revealed that patients with CPA with affected area
      of more than one lung lobe had increased risk (odds ratio, 10.20; 95% confidence
      interval, 1.49-69.77; p = 0.018). CONCLUSION: CPA recurrence can be seen in about
      one-third of cases after discontinuing azole treatment. We should make decisions
      about treatment duration and follow up depending on the severity of each case,
      particularly on the expansion of CPA-affected area.

PMID- 24679656
TI  - Advanced proximal neoplasia of the colon in average-risk adults.
AB  - BACKGROUND: Estimating risk for advanced proximal neoplasia (APN) based on distal
      colon findings can help identify asymptomatic persons who should undergo
      examination of the proximal colon after flexible sigmoidoscopy (FS) screening.
      OBJECTIVE: We aimed to determine the risk of APN by most advanced distal finding
      among an average-risk screening population. DESIGN: Prospective, cross-sectional
      study. SETTING: Teaching hospital and colorectal cancer screening center.
      PATIENTS: A total of 4651 asymptomatic persons at average risk for colorectal
      cancer aged 50 to 74 years (54.4% women [n = 2529] with a mean [+/- standard
      deviation] age of 58.4 +/- 6.2 years). INTERVENTIONS: All participants underwent
      a complete colonoscopy, including endoscopic removal of all polyps. MAIN OUTCOME
      MEASUREMENTS: We explored associations between several risk factors and APN.
      Logistic regression was used to identify independent predictors of APN. RESULTS:
      A total of 142 persons (3.1%) had APN, of whom 85 (1.8%) had isolated APN (with
      no distal findings). APN was associated with older age, a BMI >27 kg/m(2),
      smoking, distal advanced adenoma and/or cancer, and distal non-advanced tubular
      adenoma. Those with a distal advanced neoplasm were more than twice as likely to
      have APN compared with those without distal lesions. LIMITATIONS: Distal findings
      used to estimate risk of APN were derived from colonoscopy rather than FS itself.
      CONCLUSION: In persons at average risk for colorectal cancer, the prevalence of
      isolated APN was low (1.8%). Use of distal findings to predict APN may not be the
      most effective strategy. However, incorporating factors such as age (>65 years),
      sex, BMI (>27 kg/m(2)), and smoking status, in addition to distal findings,
      should be considered for tailoring colonoscopy recommendations. Further
      evaluation of risk stratification approaches in other asymptomatic screening
      populations is warranted.

PMID- 24679655
TI  - Facilitating endoscopic submucosal dissection: the suture-pulley method
      significantly improves procedure time and minimizes technical difficulty compared
      with conventional technique: an ex vivo study (with video).
AB  - BACKGROUND: The lack of countertraction in endoscopic submucosal dissection (ESD)
      results in increased technical demand and procedure time. Although the suture
      pulley method for countertraction has been reported, its effectiveness compared
      with the traditional ESD technique remains unclear. OBJECTIVE: To objectively
      analyze efficacy of countertraction using the suture-pulley method for ESD.
      DESIGN: Prospective ex vivo animal study. SETTING: Animal laboratory.
      INTERVENTIONS: Twenty simulated gastric lesions were created in porcine stomachs
      by using a standard circular template 30 mm in diameter. In the control arm (n =
      10), ESD was performed by using the standard technique. In the suture-pulley arm
      (N = 10), a circumferential incision was made, and an endoscopic suturing device
      was used to place the suture pulley. MAIN OUTCOME MEASUREMENTS: The primary
      outcome of this study was total procedure time. RESULTS: The median total
      procedure time with the suture-pulley method was significantly shorter than the
      traditional ESD technique (median, 25% to 75%, interquartile range [IQR]: 531
      seconds [474.3-549.3 seconds] vs 845 seconds [656.3-1547.5 seconds], P < .001).
      The median time (IQR) for suture-pulley placement was 160.5 seconds (150.0-168.8
      seconds). Although there was a significantly longer procedure time for proximal
      versus middle/lower stomach lesions with traditional ESD (median, 1601 seconds;
      IQR, 1547.5-1708.8 seconds vs median, 663 seconds; IQR, 627.5-681.8 seconds; P =
      .01), there was no significant difference in procedure time for lesions of
      various locations when using the suture-pulley method. Compared with traditional
      ESD, the suture-pulley method was less demanding in all categories evaluated by
      the NASA Task Load Index. LIMITATIONS: Ex vivo study. CONCLUSIONS: The suture
      pulley method facilitates direct visualization of the submucosal layer during ESD
      and significantly reduces procedure time and technical difficulty. In addition,
      the benefit of the suture-pulley method was seen for both simple and more
      complicated ESDs.

PMID- 24679657
TI  - Closure methods in submucosal endoscopy.

PMID- 24679658
TI  - Variation in polyp size estimation among endoscopists and impact on surveillance
      intervals.
AB  - BACKGROUND: Accurate estimation of polyp size is important because it is used to
      determine the surveillance interval after polypectomy. OBJECTIVE: To evaluate the
      variation and accuracy in polyp size estimation among endoscopists and the impact
      on surveillance intervals after polypectomy. DESIGN: Web-based survey.
      PARTICIPANTS: A total of 873 members of the American Society for Gastrointestinal
      Endoscopy. INTERVENTIONS: Participants watched video recordings of 4
      polypectomies and were asked to estimate the polyp sizes. MAIN OUTCOME
      MEASUREMENTS: Proportion of participants with polyp size estimates within 20% of
      the correct measurement and the frequency of incorrect surveillance intervals
      based on inaccurate size estimates. RESULTS: Polyp size estimates were within 20%
      of the correct value for 1362 (48%) of 2812 estimates (range 39%-59% for the 4
      polyps). Polyp size was overestimated by >20% in 889 estimates (32%, range 15%
      49%) and underestimated by >20% in 561 (20%, range 4%-46%) estimates. Incorrect
      surveillance intervals because of overestimation or underestimation occurred in
      272 (10%) of the 2812 estimates (range 5%-14%). Participants in a private
      practice setting overestimated the size of 3 or of all 4 polyps by >20% more
      often than participants in an academic setting (difference = 7%; 95% confidence
      interval, 1%-11%). LIMITATIONS: Survey design with the use of video clips.
      CONCLUSION: Substantial overestimation and underestimation of polyp size occurs
      with visual estimation leading to incorrect surveillance intervals in 10% of
      cases. Our findings support routine use of measurement tools to improve polyp
      size estimates.

PMID- 24679659
TI  - Endoscopic stenting in bile duct cancer increases liver volume.
AB  - BACKGROUND: Objective evaluation tools for assessing the effectiveness of
      stenting in palliative treatment of malignant biliary obstruction are not
      satisfactory. Effects of biliary stenting on liver volume change have never been
      studied. OBJECTIVE: We aimed to use volumetry to analyze liver volume changes
      after endoscopic stenting in bile duct cancer according to the location and
      number of stents. DESIGN: Retrospective review. SETTING: University hospital.
      PATIENTS: Patients with a diagnosis of hilar or distal bile duct cancer and who
      underwent biliary metal stenting. INTERVENTIONS: ERCP with self-expandable metal
      stent placement. MAIN OUTCOME MEASUREMENTS: Liver volume change after biliary
      stenting and its comparison according to the location (hilar vs distal common
      bile duct) and number (hilar bilateral vs hilar unilateral). RESULTS: There were
      60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent
      and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean
      follow-up duration was 11.7 +/- 4.9 weeks. Liver volume increased 17.4 +/- 24.1%.
      The rate of liver growth was rapid during the early period from 4 to 8 weeks.
      Stenting in hilar bile duct cancer tended to increase liver volume more than
      distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer,
      unilateral and bilateral stents showed similar liver volume increases (20.1% and
      25.8%, respectively; P = .512). LIMITATIONS: Single center, retrospective.
      CONCLUSIONS: Biliary stenting markedly increased liver volume in both hilar and
      distal bile duct cancer. Our data suggest that liver volume assessment could be a
      useful tool for evaluating stent efficacy.

PMID- 24679660
TI  - Endoscopic removal of gastric bezoars: an easy technique.

PMID- 24679661
TI  - Technique of FNA and biopsy by using a needle with side fenestration in
      pancreatic cystic lesions.

PMID- 24679662
TI  - Recovering a stuck capsule ... and discovering a rare small-intestinal
      adenocarcinoma.

PMID- 24679663
TI  - An efficient process for lactic acid production from wheat straw by a newly
      isolated Bacillus coagulans strain IPE22.
AB  - A thermophilic lactic acid (LA) producer was isolated and identified as Bacillus
      coagulans strain IPE22. The strain showed remarkable capability to ferment
      pentose, hexose and cellobiose, and was also resistant to inhibitors from
      lignocellulosic hydrolysates. Based on the strain's promising features, an
      efficient process was developed to produce LA from wheat straw. The process
      consisted of biomass pretreatment by dilute sulfuric acid and subsequent SSCF
      (simultaneous saccharification and co-fermentation), while the operations of
      solid-liquid separation and detoxification were avoided. Using this process,
      46.12 g LA could be produced from 100g dry wheat straw with a supplement of 10
      g/L corn steep liquid powder at the cellulase loading of 20 FPU (filter paper
      activity units)/g cellulose. The process by B. coagulans IPE22 provides an
      economical route to produce LA from lignocellulose.

PMID- 24679664
TI  - A vaccine against serogroup B Neisseria meningitidis: dealing with uncertainty.
AB  - Neisseria meningitidis is an important cause of invasive bacterial infection in
      children worldwide. Although serogroup C meningococcal disease has all but
      disappeared in the past decade as a direct result of immunisation programmes in
      Europe, Canada, and Australia, meningitis and septicaemia caused by serogroup B
      meningococci remain uncontrolled. A vaccine (4CMenB) has now been licensed for
      use in the European Union, comprising three immunogenic antigens (identified with
      use of reverse vaccinology) combined with bacterial outer-membrane vesicles. The
      vaccine has the potential to reduce mortality and morbidity associated with
      serogroup B meningococci infections, but uncertainty remains about the breadth of
      protection the vaccine might induce against the diverse serogroup B meningococci
      strains that cause disease. We discuss drawbacks in the techniques used to
      estimate coverage and potential efficacy of the vaccine, and their effects on
      estimates of cost-effectiveness, both with and without herd immunity. For
      parents, and clinicians treating individual patients, the predicted benefits of
      vaccination outweigh existing uncertainties if any cases can be prevented, but
      future use of the vaccine must be followed by rigorous post-implementation
      surveillance to reassess its value to health systems with directly recorded
      epidemiological data. 

PMID- 24679665
TI  - Attentional biases in irritable bowel syndrome patients.
AB  - BACKGROUND AND OBJECTIVE: According to the cognitive behavioural model of
      irritable bowel syndrome (IBS) selective attention to visceral stimuli is one of
      the pathophysiological mechanisms in IBS. We aimed to investigate attentional
      biases in patients with IBS and to explore the relationship between neuroticism,
      trait anxiety, visceral anxiety and indices of attentional biases. METHODS:
      Twenty-seven patients completed the global/local task and the modified Stroop
      task (using 4 word categories: neutral, symptom-related, emotionally and
      situationally relevant) while 28 healthy persons completed the Stroop task only.
      Both groups also filled out a set of psychological questionnaires. RESULTS: The
      results show two distinct attentional biases in patients with irritable bowel
      syndrome. The index of global precedence was negatively correlated with
      neuroticism (r=-.41, P<.05) while there was no correlation of global precedence
      with trait and visceral anxiety. We found Stroop facilitation (F[3,81]=3.98,
      P<.02) specifically for situational threat words. Also, there were positive
      correlations between trait anxiety, visceral anxiety and the Stroop facilitation
      index for situational threat words (r=.43 and r=.47, P<.05). In the control
      group, we found neither Stroop facilitation nor interference. But, facilitation
      index of emotional words was positively correlated with neuroticism (r=.40,
      P<.05), which is in line with the "emotion congruent attentional bias" in the
      general population. CONCLUSIONS: Neuroticism was associated with the reduction in
      global precedence observed in the global/local task. Trait anxiety and visceral
      anxiety were associated with Stroop facilitation elicited by situational threat
      words, which are of particular concern for patients with irritable bowel
      syndrome. These specific situations do not elicit an attentional bias in healthy
      participants, which might indicate that the observed facilitation to situational
      threat words is unique for IBS patients.

PMID- 24679666
TI  - NOD2/CARD15 and IL23R genetic variability in 204 Algerian Crohn's disease.
AB  - NOD2/CARD15 and IL23R gene variants play an important role in the susceptibility
      to Crohn's disease (CD). Studies of genotype-phenotype relationship suggest that
      these variants are associated with the development of the disease and specific
      phenotype. Preliminary reports analyzing the association between these variants
      have never been made on Algerian CD's. In a case-control design, 204 Algerian
      with CD diagnosed for at least 5years and 201 controls were included were
      genotyped for single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene R702W
      (SNP8, rs2066844), G908R (SNP12, rs2066845) and IL23R R381Q (rs11209026) gene
      variants were determined using the TaqMan SNP genotyping assays. NOD2/CARD15 908R
      was carried by 3% of the patients and none in control subjects (chi(2)=8.6,
      Pc=0.003, OR=13.20). NOD2/CARD15 702W was associated to CD outcome (chi(2)=17.2,
      Pc=0.00003, OR=12.5) and early onset of disease (group A1, chi(2)=19.3, Pc=1.10(
      5), OR=14.05, PM-H=2.10(-6)). IL23R 381Q variants was more frequent in CD's
      patients than controls (chi(2)=8, Pc=0.005, OR=3.48), it was associated to
      earlier onset (group A1, chi(2)=7.1, Pc=0.007, OR=1.04, PM-H=0.002), extra
      intestinal manifestations (EIM) outcome (chi(2)=10.6, Pc=0.001, OR=1.05, PM
      H=0.002) and ileocolonic location (chi(2)=6.8, Pc=0.009, OR=1.05, PM-H=0.001). In
      this Algerian cohort, NOD2/CARD15 and IL23R variants were associated with CD's
      outcomes and linked to a particular clinical phenotype. 

PMID- 24679667
TI  - Gene therapy: a novel way to treat respiratory failure?
AB  - Respiratory failure leads to tissue hypoxia and subsequent organ damage. The
      crocodile hemoglobin affinity for oxygen is significantly reduced in the presence
      of CO2, allowing crocodiles to stay under water for more than 1h. The crocodile
      bicarbonate effect can possibly be transplanted into the human hemoglobin by
      replacing only five and seven amino acid residues in the beta-globin and alpha
      globin chains, respectively. The resulting hybrid formed by these modified chains
      has been named Scuba hemoglobin. The in vitro production of Scuba hemoglobin by
      human hematopoietic stem cells and their reintroduction into the blood could be
      an interesting tool to improve tissue oxygenation in patients suffering from
      respiratory failure. 

PMID- 24679668
TI  - Conditioned medium derived from mesenchymal stem cells culture as a intravesical
      therapy for cystitis interstitials.
AB  - The treatment of Interstinal Cystitisis (IC) is still challenge for urologist.
      Available therapies do not result in long-term control of symptoms and do not
      provide pain relive to patients. Unique abilities of mesenchymal stem cells (MSC)
      could be used to develop new treatment approaches for Interstitial Cystitis.
      Conditioned Medium (CM) derived from MSC culture is rich in plenty of growth
      factors, cytokines and trophic agents which were widely reported to enhance
      regeneration of urinary bladder in different conditions. This ready mixture of
      growth factors could be used to develop intravesical therapy for patients with
      IC. MSC-CM has anti-apoptotic, anti-inflammatory, supportive, angiogenic,
      immunosuppressive and immunomodulative properties and seems to be ideal substance
      to prevent IC recurrence and to create favorable environment for regeneration of
      damaged bladder wall. 

PMID- 24679669
TI  - Clinical features of prefrail older individuals and emerging peripheral
      biomarkers: a systematic review.
AB  - Frailty is a geriatric syndrome characterized by the clinical presentation of
      identifiable physical alterations such as loss of muscle mass and strength,
      energy and exercise tolerance, and decreased physiological reserve. Individuals
      with one or two of these alterations are defined as prefrail. The clinical
      features of prefrail older individuals have been investigated to a lesser extent
      compared to the frail population, even though this intermediate stage may provide
      insights into the mechanisms involved in the physical decline associated with
      aging and it is considered to be potentially reversible. We performed searches in
      the Medline, Embase, Scopus, Cinahl, and Cochrane databases from January 1995 to
      July 2013 for papers about the identification of prefrail people aged 65 and
      older published either in English or Spanish, and the reference lists of from the
      articles retrieved were pearled in order to identify any which may have been
      missed in the initial search. Two independent reviewers extracted descriptive
      information on frailty criteria and outcomes from the selected papers: of the 277
      articles retrieved from the searches and 25 articles retrieved from pearling, 84
      met the study inclusion criteria. The prevalence of prefrailty ranges between 35%
      and 50% in individuals aged over 60, is more common in women, and the age and the
      number of comorbidities in these individuals is similar to their frail
      counterparts. Weakness is the most prevalent symptom in prefrail individuals
      although there are some sex differences. Some serum biomarkers seem to
      discriminate prefrail from non-frail individuals but further research would be
      required to confirm this. 

PMID- 24679670
TI  - Antimicrobial use in Hungarian long-term care facilities: high proportion of
      quinolone antibacterials.
AB  - The aim of this survey was to estimate the burden of antimicrobial use and to
      describe the determinants for antimicrobial use in Hungarian long-term care
      facilities (LTCFs) in order to increase the attention given to the proper
      prescription for this vulnerable population. A one-day point-prevalence study was
      undertaken between April and May 2013. Data on resident treated with an
      antibacterial, antimycotic or tuberculostatic for systemic use were collected
      prospectively on a single day in each participating LTCF with over 50 beds.
      Descriptive statistics were used to present the data. 91 LTCFs with 11,823
      residents participated in this survey. 156 residents (1.3%) were given
      antimicrobials. 96.8% of antimicrobials were mostly prescribed for therapy
      included urinary tract infections (40.3%), respiratory tract infections (38.4%)
      and skin and soft tissue infections (13.2%). The most common therapeutic
      antimicrobials (97.5%) belonged to the ATC J01 class of 'antibacterials for
      systemic use'. The most important J01 subclasses were J01M quinolone
      antibacterials (32.7%), J01C beta-lactam antibacterials (25.2%), J01D other beta
      lactam antibacterials (11.3%) and J01F macrolides, lincosamides and
      streptogramins (11.3%). Antimicrobials were mostly prescribed empirically whereas
      3.8% was microbiologically documented treatments. 3.2% of all prescribed
      antimicrobials were prescribed for the prophylaxis of urinary tract infections
      (60%) and ear, nose, mouth infections (40%). Our results emphasize the need of a
      national recommendation for good practice in LTCFs in order to avoid
      inappropriate antimicrobial therapy leading to spread of multidrug resistant
      pathogens. In addition, continuing education of prescribers on antimicrobial
      treatment is essential. 

PMID- 24679671
TI  - Developing medical educators--a mixed method evaluation of a teaching education
      program.
AB  - BACKGROUND: It is well accepted that medical faculty teaching staff require an
      understanding of educational theory and pedagogical methods for effective medical
      teaching. The purpose of this study was to evaluate the effectiveness of a 5-day
      teaching education program. METHODS: An open prospective interventional study
      using quantitative and qualitative instruments was performed, covering all four
      levels of the Kirkpatrick model: Evaluation of 1) 'Reaction' on a professional
      and emotional level using standardized questionnaires; 2) 'Learning' applying a
      multiple choice test; 3) 'Behavior' by self-, peer-, and expert assessment of
      teaching sessions with semistructured interviews; and 4) 'Results' from student
      evaluations. RESULTS: Our data indicate the success of the educational
      intervention at all observed levels. 1) Reaction: The participants showed a high
      acceptance of the instructional content. 2) Learning: There was a significant
      increase in knowledge (P<0.001) as deduced from a pre-post multiple-choice
      questionnaire, which was retained at 6 months (P<0.001). 3) Behavior: Peer-, self
      , and expert-assessment indicated a transfer of learning into teaching
      performance. Semistructured interviews reflected a higher level of
      professionalism in medical teaching by the participants. 4) Results: Teaching
      performance ratings improved in students' evaluations. CONCLUSIONS: Our results
      demonstrate the success of a 5-day education program in embedding knowledge and
      skills to improve performance of medical educators. This multimethodological
      approach, using both qualitative and quantitative measures, may serve as a model
      to evaluate effectiveness of comparable interventions in other settings.

PMID- 24679672
TI  - Cost-effectiveness and cost-utility of selective serotonin reuptake inhibitors,
      serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants in
      depression with comorbid cardiovascular disease.
AB  - OBJECTIVE: There is a lack of clarity in the literature regarding the cost
      effectiveness and cost-utility of antidepressants for treating real-world
      patients. The impact of comorbid cardiovascular disease (CVD) on the economic
      evaluations of antidepressants remains to be determined. METHOD: Adult patients
      prescribed with antidepressants for depression were identified from the National
      Health Insurance Research Database in Taiwan. A cost-effectiveness and cost
      utility analysis was conducted comparing selective serotonin reuptake inhibitors
      (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and tricyclic
      antidepressants (TCAs), and by the presence of comorbid CVD. RESULTS: In terms of
      treatment success rates, SSRIs were the most cost-effective option compared to
      TCAs and SNRIs as revealed in the incremental cost-effectiveness ratios. The cost
      effectiveness acceptability curves further showed differential findings in the
      cost-utility results by the presence of comorbid CVD. CONCLUSION: To improve
      treatment success rates and quality-adjusted life years, SSRIs can be considered
      the most cost-effective option. Future research is needed to further clarify the
      impacts of physical comorbidities and other associated factors on the cost
      effectiveness and cost-utility of pharmacological treatments in patients with
      depression.

PMID- 24679674
TI  - Pharmacological characterization of actin-binding (-)-doliculide.
AB  - Natural compounds offer a broad spectrum of potential drug candidates against
      human malignancies. Several cytostatic drugs, which are in clinical use for
      decades, derive directly from natural sources or are synthetically optimized
      derivatives of natural lead structures. An eukaryote target molecule to which
      many natural derived anti-cancer drugs bind to is the microtubule network. Of
      similar importance for the cell is the actin cytoskeleton, responsible for cell
      movements, migration of cells and cytokinesis. Nature provides also a broad range
      of compounds directed against actin as intracellular target, but none of these
      actin-targeting compounds has ever been brought to clinical trials. One reason
      why actin-binding compounds have not yet been considered for further clinical
      investigations is that little is known about their pharmacological properties in
      cancer cells. Herein, we focused on the closer characterization of doliculide, an
      actin binding natural compound of marine origin in the breast cancer cell lines
      MCF7 and MDA-MB-231. We used fluorescence-recovery-after-photobleaching (FRAP)
      analysis to determine doliculide's early effects on the actin cytoskeleton and
      rhodamin-phalloidin staining for long-term effects on the actin CSK. After
      validating the disruption of the actin network, we further investigated the
      functional effects of doliculide. Doliculide treatment leads to inhibition of
      proliferation and impairs the migratory potential. Finally, we could also show
      that doliculide leads to the induction of apoptosis in both cell lines. Our data
      for the first time provide a closer characterization of doliculide in breast
      cancer cells and propagate doliculide for further investigations as lead
      structure and potential therapeutic option as actin-targeting compound. 

PMID- 24679673
TI  - Structural elucidation and synthesis of vialinin C, a new inhibitor of TNF-alpha
      production.
AB  - A new inhibitor of TNF-alpha production (IC50=0.89 MUM) named vialinin C (1) was
      isolated from dry fruiting bodies of an edible Chinese mushroom, Thelephora
      vialis. The structure of 1 was determined by high-resolution MS, NMR
      spectroscopic analysis, and confirmed by synthesis. Synthesis of ganbajunin B (5)
      obtained from the same origin was also described.

PMID- 24679676
TI  - Management of the complications of traditional bone setting for upper extremity
      fractures: the experiences of a French Forward Surgical Team in Chad.
AB  - The practice of traditional bone setting (TBS) in sub-Saharan Africa often leads
      to severe complications after upper extremity fracture. The purpose of this study
      was to evaluate the management of these complications by a French Forward
      Surgical Team deployed in Chad. An observational, prospective study was conducted
      over a six-month period between 2010 and 2011. During this period 28 patients
      were included. There were 20 males and 8 females with a mean age of 30.6 years
      (range 5-65 years). Thirteen patients (47%) had mal-union of their fracture, nine
      had non-union (32%), three children (10.5%) presented gangrene and three patients
      (10.5%) suffered from other complications. Fifteen (54%) patients did not undergo
      a corrective procedure either because it was not indicated or because they
      declined. Only 13 (46%) patients were operated on. Twelve of these patients were
      reviewed with a mean follow-up of 2.4 months. All of them were satisfied with
      conventional treatment. The infection seemed to be under control in every septic
      patient. Bone union could not be evaluated in most patients because of the short
      follow-up. Management of TBS complications is always challenging, even in a
      deployed Western medical treatment facility. Surgical expectations should be low
      because of the severity of the sequelae and the uncertainty of patient follow-up.
      Prevention remains the best treatment. 

PMID- 24679677
TI  - Low frequency ultrasound (42 kHz) assisted degradation of Acid Blue 113 in the
      presence of visible light driven rare earth nanoclusters loaded TiO2
      nanophotocatalysts.
AB  - An attempt has been made to render the visible light driven photocatalytic
      activity to the TiO2 nanocatalysts by loading 1 wt% of rare earth (RE)
      nanoclusters (Gd(3+), Nd(3+) and Y(3+)) using a low frequency (42 kHz) producing
      commercial sonicator. The STEM-HAADF analysis confirms that the RE nanoclusters
      were residing at the surface of the TiO2. Transmission electron microscopic (TEM)
      and X-ray diffraction (XRD) analyses confirm that the loading of RE nanoclusters
      cannot make any significant changes in the crystal structure of TiO2. However,
      the optical properties of the resulted nanocatalysts were significantly modified
      and the nanocatalysts were employed to study the sonocatalytic, photocatalytic
      and sonophotocatalytic decolorization as well as mineralization of Acid Blue 113
      (AB113). Among the experimented nanocatalysts maximum degradation of AB113 was
      achieved in the presence Y(3+)-TiO2 nanocatalysts. The decolorization of AB113 in
      the presence and absence of Y(3+) loaded TiO2 ensues the following order
      sonolysis<photocatalysis<sonocatalysis<sonophotocatalysis. The sonophotocatalytic
      decolorization of AB113 shows 1.4-fold (synergy index) enhanced rate when
      compared with the two corresponding individual advanced oxidation processes. The
      sonophotocatalytic mineralization shows that 65% of total organic carbon (TOC)
      can be removed from AB113 after the 5h of continuous irradiation however the
      mineralization cannot be able to show the synergetic effect.

PMID- 24679678
TI  - Influence of the meteorological input on the atmospheric transport modelling with
      FLEXPART of radionuclides from the Fukushima Daiichi nuclear accident.
AB  - In the present paper the role of precipitation as FLEXPART model input is
      investigated for one possible release scenario of the Fukushima Daiichi accident.
      Precipitation data from the European Center for Medium-Range Weather Forecast
      (ECMWF), the NOAA's National Center for Environmental Prediction (NCEP), the
      Japan Meteorological Agency's (JMA) mesoscale analysis and a JMA radar-rain gauge
      precipitation analysis product were utilized. The accident of Fukushima in March
      2011 and the following observations enable us to assess the impact of these
      precipitation products at least for this single case. As expected the differences
      in the statistical scores are visible but not large. Increasing the ECMWF
      resolution of all the fields from 0.5 degrees  to 0.2 degrees  rises the
      correlation from 0.71 to 0.80 and an overall rank from 3.38 to 3.44. Substituting
      ECMWF precipitation, while the rest of the variables remains unmodified, by the
      JMA mesoscale precipitation analysis and the JMA radar gauge precipitation data
      yield the best results on a regional scale, specially when a new and more robust
      wet deposition scheme is introduced. The best results are obtained with a
      combination of ECMWF 0.2 degrees  data with precipitation from JMA mesoscale
      analyses and the modified wet deposition with a correlation of 0.83 and an
      overall rank of 3.58. NCEP-based results with the same source term are generally
      poorer, giving correlations around 0.66, and comparatively large negative biases
      and an overall rank of 3.05 that worsens when regional precipitation data is
      introduced. 

PMID- 24679680
TI  - Hypertonic saline with furosemide for the treatment of acute congestive heart
      failure: a systematic review and meta-analysis.
AB  - BACKGROUND: Advanced congestive heart failure (CHF) therapies include intravenous
      inotropic agents, change in class of diuretics, and venous ultrafiltration or
      hemodialysis. These modalities have not been associated with improved prognosis
      and are limited by availability and cost. Compared to high-dose furosemide alone,
      concomitant hypertonic saline solution (HSS) administration has demonstrated
      improved clinical outcomes with good safety profile. METHODS: A literature search
      was conducted for randomized controlled trials that investigated the use of HSS
      in patients admitted to hospital with acute CHF. RESULTS: 1032 patients treated
      with HSS and 1032 controls, demonstrated decreased all-cause mortality in
      patients treat with HSS with RR of 0.56 (95% CI 0.41-0.76,p=0.0003). 1012
      patients treated with HSS and 1020 controls, demonstrated decreased heart failure
      hospital readmission with RR of 0.50 (95% CI 0.33-0.76,p=0.001). Patients treated
      with HSS also demonstrated decreased hospital length of stay (p=0.0002), greater
      weight loss (p<0.00001), and preservation of renal function (p<0.00001).
      CONCLUSION: The results of this meta-analysis demonstrate that in patients with
      advanced CHF concomitant hypertonic saline administration improved weight loss,
      preserved renal function, and decreased length of hospitalization, mortality and
      heart failure rehospitalization. A future adequately powered, multi-centre,
      placebo controlled, randomized, double dummy, blinded trial is needed to assess
      the benefit of hypertonic saline in patients with renal dysfunction, in diverse
      patient populations, as well using a patient population on optimal current heart
      failure treatment. Pending further validation, there is promise for hypertonic
      saline as an advanced therapy for the management of acute advanced CHF.

PMID- 24679681
TI  - Clinical predictors of response to anakinra in patients with heart failure.

PMID- 24679679
TI  - Relative validity and reliability of an FFQ in youth with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the relative validity and reliability of the SEARCH FFQ
      that was modified from the Block Kids Questionnaire. DESIGN: Study participants
      completed the eighty-five-item FFQ twice plus three 24 h dietary recalls within
      one month. We estimated correlations between frequencies obtained from
      participants with the true usual intake for food groups and nutrients, using a
      two-part model for episodically consumed foods and measurement error adjustment.
      SETTING: The multi-centre SEARCH for Diabetes in Youth Nutrition Ancillary Study.
      SUBJECTS: A subgroup of 172 participants aged 10-24 years with type 1 diabetes.
      RESULTS: The mean correlations, adjusted for measurement error, of food groups
      and nutrients between the FFQ and true usual intake were 0.41 and 0.38,
      respectively, with 57 % of food groups and 70 % of nutrients exhibiting
      correlations >0.35. Correlations were high for low-fat dairy (0.80), sugar
      sweetened beverages (0.54), cholesterol (0.59) and saturated fat (0.51), while
      correlations were poor for high-fibre bread and cereal (0.16) and folate (0.11).
      Reliability of FFQ intake based on two FFQ administrations was also reasonable,
      with 54 % of Pearson correlation coefficients >=0.5. Reliability was high for low
      fat dairy (0.7), vegetables (0.6), carbohydrates, fibre, folate and vitamin C
      (all 0.5), but less than desirable for low-fat poultry and high-fibre bread,
      cereal, rice and pasta (0.2-0.3). CONCLUSIONS: While there is some room for
      improvement, our findings suggest that the SEARCH FFQ performs quite well for the
      assessment of many nutrients and food groups in a sample of youth with type 1
      diabetes.

PMID- 24679682
TI  - Ventricular wall stress and late gadolinium enhancement in patients with
      Takotsubo syndrome: more data worth contemplating about.

PMID- 24679683
TI  - Right coronary artery aneurysm due to Kawasaki disease: a comprehensive
      assessment by multislice computed tomography.

PMID- 24679684
TI  - Prognostic role of stress/rest myocardial perfusion scintigraphy in patients with
      cardiac syndrome x.
AB  - AIM: The prognostic utility of myocardial perfusion scintigraphy (MPS) in
      patients with angiographically normal coronary arteries has not been evaluated
      yet. Our aim was to determine the prognostic role of positive MPS in patients
      with angina, positive exercise test and smooth coronary arteries (syndrome X).
      METHODS: A total of 156 patients with angina, positive exercise test, positive
      MPS and normal coronary arteries and 172 patients with angina and positive
      exercise test who had negative MPS were selected for study. The primary endpoint
      was combined all-cause mortality and hospitalizations for cardiac causes. The
      secondary endpoint was hospitalization for cardiac causes. RESULTS: Kaplan-Meier
      analysis showed a greater (p=0.001) incidence of the primary endpoint in patients
      with positive MPS, compared to those with negative MPS. Additionally, Kaplan
      Meier analysis for cardiovascular hospitalization showed a significant difference
      (p=0.003) between the two groups. Cox regression analysis, adjusted for age, sex,
      BMI and antianginal therapy confirmed a significant risk increase for patients
      with positive MPS, with a hazard ratio (HR)=3.20 (CI 95%: 1.14-9.02; p=0.028).
      Cox analysis for cardiovascular hospitalization also showed a significant risk
      increase for patients with positive MPS (HR=3.19; CI 95%: 1.13-9.00; p=0.03).
      Finally, Cox analysis showed that patients with positive MPS tend to have a
      higher risk to remain symptomatic in the follow-up period (HR=1.614; CI 95%:
      0.999-2.607; p=0.51). CONCLUSIONS: This study shows that inducible myocardial
      hypoperfusion at MPS in patients with syndrome X could discriminate patients with
      a more severe prognosis, especially in terms of further hospitalization and
      symptomatic burden.

PMID- 24679685
TI  - Rate ratio for mortality by Poisson's regression analysis: limitation on
      predictive ability for the individual events.

PMID- 24679686
TI  - Dual antiplatelet therapy versus warfarin anticoagulation in patients undergoing
      catheter ablation of atrial fibrillation.

PMID- 24679687
TI  - Medieval roots of modern knowledge regarding carotid sinus syncope.

PMID- 24679688
TI  - Dexamethasone for the prevention of acute mountain sickness: systematic review
      and meta-analysis.
AB  - BACKGROUND: AMS is a disease that occurs when accessing high altitude (HA) or
      upon exposure to a higher altitude after acclimatising over 3,000 m. Evidence
      shows that drugs can prevent AMS. The function of dexamethasone for preventing
      AMS is important. No systematic review has previously been published about the
      effect of dexamethasone. The effect of intervention is unclear, which has limited
      the use of dexamethasone in the prevention of AMS. METHODS: We searched PubMed
      and Embase for studies from inception to July 2013. We selected randomised
      controlled trials including dexamethasone versus placebo as prophylaxis for AMS.
      The studies included were required to provide a clear dose of dexamethasone, the
      final altitude and clear diagnostic criteria used to judge the AMS severity of
      symptoms and incidence. Finally, 8 studies were included in this review. There
      were 116 participants in the experimental groups and 110 in the control groups.
      Three different doses of dexamethasone were used in these studies (8, 12, and 16
      mg/d). RESULT: Eight of the 79 considered studies were eventually added to the
      meta-analysis. We used the fixed-effect model (RevMan 5.0) based on the
      heterogeneity (I(2)=0%, p=0.43). Dexamethasone could reduce the incidence of AMS
      with an odds ratio of 6.03 (95% CI, 2.23 to 21.00) for dexamethasone compared
      with placebo; the p value for overall effect was less than 0.00001. CONCLUSIONS:
      Our systematic review suggests that oral dexamethasone is effective in preventing
      AMS. Additionally, there is some evidence that the effect of dexamethasone is
      related to height and dosage.

PMID- 24679689
TI  - Dynamic induction of pro-angiogenic milieu after transplantation of marrow
      derived mesenchymal stem cells in experimental myocardial infarction.
AB  - BACKGROUND: Cell-based pro-angiogenic therapy by bone marrow mesenchymal stem
      cells (MSCs) has been touted as a means to reducing the adverse effects of
      cardiac remodeling after myocardial infarction (MI). Milieu-dependent regulation
      of pro-angiogenic potential of MSCs after infarction remains to be elucidated. In
      this study, the effects of marrow-derived MSCs on the kinetics of angiogenesis
      signaling factors were investigated in a rabbit model of MI. METHODS: MI was
      induced in rabbits, and the animals were randomized into two groups (cell
      transplantation and control, each group with 21 animals). 1 * 10(6) autologous
      marrow-derived MSCs were injected into the myocardium of the border zone after
      transfection with a green fluorescent protein (GFP) lentiviral reporter vector.
      Control animals received PBS vehicle only. Effect of the transplanted cells on
      the hearts was evaluated over time by pathological, immunofluorescence, western
      blotting, immuno-electron microscopy, and echocardiographic analyses. RESULTS:
      Transplanted GFP-positive MSCs were enriched with time in the peri-infarct border
      zone with differentiation potential into three major cell types of the heart,
      including cardiomyocytes, endothelial cells, and smooth muscle cells, and there
      was significant augmentation of microvascular density. The transplanted cells
      could change the milieu of the injured myocardium to increase the expression
      levels of VEGF as well as the ratio of Ang-2 to Ang-1, and to reduce the ratio of
      phosphorylated Tie2 to Tie2. CONCLUSION: An angiogenesis-promoting milieu was
      induced after the transplantation of marrow MSCs in the injured myocardium.
      Compared with the resident cells, the transplanted cells had a greater rate of
      cellular kinetics in the infarcted myocardium.

PMID- 24679690
TI  - Serial contrast enhanced cardiac computed tomography to assess extensive peri
      aortic abscess following Bentall procedure.

PMID- 24679691
TI  - Altered atherosclerotic-related gene expression signature in circulating
      mononuclear leukocytes from hypercholesterolemic patients with low HDL
      cholesterol levels.

PMID- 24679692
TI  - Frequency of cardiovascular diseases and risk factors treated in France according
      to social deprivation and residence in an overseas territory.
AB  - BACKGROUND: The frequencies of treated cardiovascular disease (CVD) and their
      associated risk factors (CVRF) may vary according to socioeconomic and
      territorial characteristics. METHODS: These frequencies have been described for
      48million policyholders of the French general health insurance scheme, according
      to a metropolitan geographical deprivation index in five quintiles (from the
      least to the most deprived: Q1 to Q5), the existence of universal complementary
      health cover (CMUC) in individuals under the age of 60, and residence in a French
      overseas territory (FOT). The information system (SNIIRAM) was used to identify
      CVDs and anti-diabetic, anti-hypertensive or lipid-lowering treatments by three
      reimbursements in 2010. RESULTS: After age- and sex-specific adjustment, the
      inhabitants of the most deprived areas more often suffered from distal arterial
      disease (Q5/Q1=1.5), coronary artery disease (1.2) and cerebral vascular accident
      (1.1), as did the CMUC beneficiaries compared to non-beneficiaries (ratios of
      1.7, 1.3 and 1.5), and the FOT residents in comparison to the most deprived
      metropolitan quintile (Q1), with the exception of coronary artery disease (1.2,
      0.6 and 1.2). Inhabitants of the most deprived areas more often received anti
      diabetic and anti-hypertensive treatment (Q5/Q1=1.4 and 1.2), as did the people
      on the CMUC (2.0 and 1.2) and the FOT inhabitants (FOT/Q1=2.4 and 1.3). These
      ratios were of 1.1, 1.0 and 0.8 for lipid-lowering drugs. CONCLUSION: These
      results pinpoint populations for which specific preventative initiatives could be
      supported. While health care service utilisation is facilitated (CMUC), it is
      probably not yet effective enough in view of the persistent increased
      cardiovascular risk.

PMID- 24679693
TI  - Does residual aortic regurgitation after transcatheter aortic valve implantation
      increase mortality in all patients? The importance of baseline natriuretic
      peptides.
AB  - BACKGROUND: Aortic regurgitation (AR) is an important complication of
      transcatheter aortic valve implantation (TAVI) and even moderate AR is associated
      with increased mortality after TAVI. The association with decreased survival is
      unclear. We aimed to analyse the impact of AR after TAVI as a function of
      baseline NT-proBNP. METHODS: We included 236 consecutive patients implanted in
      our centre with the SAPIEN and SAPIEN XT valves, via the transfemoral route. AR
      was evaluated by transthoracic echocardiography. NT-proBNP was measured 24h
      before implantation and patients were divided according to the median value.
      RESULTS: Median age was 85 years (80-89) and 137 (58.1%) were women. Patients
      with high NT-proBNP had lower left ventricular ejection fraction: 52% (35-65) vs.
      63% (55-70), p<0.001, larger telediastolic diameters: 56 mm (49-61) vs. 52 mm (46
      56), p=0.01, and more severe aortic stenosis: 0.62 +/- 0.15 cm(2) vs. 0.70 +/-
      0.2 cm(2), p<0.001. Pre-procedural moderate or severe AR (42% vs. 26%, p=0.013)
      and mitral regurgitation (56% vs. 36%, p=0.004) were more common in the high NT
      proBNP group. After TAVI, moderate or severe AR occurred in 26% of patients and
      was associated with increased 2-year mortality only in the low NT-proBNP group,
      while patients in the high NT-proBNP group were not affected. CONCLUSIONS:
      Moderate or severe AR after TAVI was not associated with increased 2-year
      mortality in patients with high baseline NT-proBNP. Our data suggest that the
      impact of AR after TAVI is absent in patients with significant pre-procedural AR
      or mitral regurgitation and more severe aortic stenosis.

PMID- 24679694
TI  - Hybrid percutaneous coronary revascularisation for a patient with left main
      bifurcation and extensive, diffuse coronary artery disease.

PMID- 24679695
TI  - Reduction of alkaline reflux gastritis and marginal ulcer by modified Braun
      enteroenterostomy in gastroenterologic reconstruction after
      pancreaticoduodenectomy.
AB  - BACKGROUND: The incidence of alkaline reflux gastritis (ARG) after
      pancreaticoduodenectomy (PD) is high. Although Braun enteroenterostomy (BEE) may
      reduce ARG, BEE may result in marginal ulcers (MUs) due to the additional
      anastomotic stoma. We conducted this study to compare clinical outcomes of using
      a modified BEE (MBEE) with traditional gastrojejunostomy (TGJ), by inducting a
      purse-string suture instead of an additional anastomotic stoma. MATERIALS AND
      METHODS: All 62 patients underwent standard PD at the Department of
      Hepatobiliopancreatic Surgery of West China Hospital between January 1, 2008 and
      January 31, 2012. Demographics, perioperative and postoperative factors, and
      follow-up morbidity were compared in those patients who underwent MBEE (n = 32,
      three patients were lost to follow-up) to those who underwent TGJ (n = 30, nine
      patients were lost to follow-up). RESULTS: Patients who underwent the MBEE
      experienced a decrease in total morbidity including ARG and MUs, relative to
      those who underwent TGJ (24.1% versus 58.3%, P = 0.011). With regard to the MBEE
      group, the total ARG rate was statistically significantly lower compared with the
      TGJ group (13.8% versus 37.5%, P = 0.046). In addition, the incidence of MUs was
      reduced. CONCLUSIONS: In patients undergoing PD, the MBEE was safely performed
      with significantly more patients having reduced incidence of ARG and related
      sequela compared with those who underwent TGJ. These results support further
      study of patients undergoing gastroenterostomy after resection of the distal
      stomach in larger, randomized studies.

PMID- 24679696
TI  - Determination of protein phosphatase type 2A in monocytes from multiple trauma
      patients: a potential biomarker for sepsis.
AB  - BACKGROUND: Protein phosphatase type 2A (PP2A) can downregulate c-Jun N-terminal
      kinase (JNK) expression in monocytes stimulated by lipopolysaccharide. However,
      this effect has not been evaluated in patients with sepsis. We sought to
      determine whether PP2A/JNK pathway is involved in sepsis and whether PP2A
      expression can be associated with patient outcome. MATERIALS AND METHODS: We
      measured PP2A, c-Jun, and JNK protein as well as PP2A and c-Jun messenger RNA in
      monocytes from trauma patients with (n = 24) or without (n = 22) sepsis 1 and 7 d
      after major trauma and from healthy volunteers (n = 15) by Western blotting and
      quantitative real-time polymerase chain reaction. Patient outcomes, including
      intensive care unit length of stay, Sequential Organ Failure Assessment score,
      and Multiple Organ Dysfunction score were compared between groups. Correlations
      between PP2A and c-Jun/JNK expression as well as patient outcomes were analyzed.
      Receiver operating characteristic analysis was performed to determine the
      diagnostic efficiency of PP2A for sepsis. RESULTS: PP2A protein and messenger RNA
      expression were significantly higher in septic patients compared with nonseptic
      patients or healthy volunteers. Conversely, the expressions of JNK and c-Jun were
      significantly reduced in septic patients and correlated inversely with PP2A
      expression. Furthermore, PP2A expression was positively associated with LOS,
      Sequential Organ Failure Assessment and Multiple Organ Dysfunction score at day 1
      and day 7. Receiver operating characteristic curve yielded a high sensitivity
      (87.5%) of PP2A in discriminating septic versus nonseptic patients. CONCLUSIONS:
      PP2A may serve as a negative regulator of the JNK pathway and a biomarker for
      sepsis.

PMID- 24679697
TI  - Cholecystostomy offers no survival benefit in patients with acute acalculous
      cholecystitis and severe sepsis and shock.
AB  - BACKGROUND: Acute acalculous cholecystitis is often managed with cholecystectomy
      or cholecystostomy, but data guiding surgical practice are lacking. MATERIALS AND
      METHODS: Longitudinal analysis of the California Office of Statewide Health
      Planning and Development Patient Discharge Data was performed from 1995-2009.
      Patients with acute acalculous cholecystitis were identified by International
      Classification of Diseases 9 code. Cox proportional hazard analysis found
      predictors of time to death, adjusting for patient demographics, sepsis, shock,
      frailty, Charlson comorbidity index, length of stay, insurance status, teaching
      hospital status, and year. RESULTS: Of 43,341 patients, 63.5% received a
      cholecystectomy, 2.8% received a cholecystostomy, and 1.2% received both.
      Overall, 30.4% of patients died, with higher mortality among patients with
      cholecystostomy (61.7%) or no procedure (42.0%) than cholecystectomy (23.0%). In
      patients with severe sepsis and shock, there was no difference in survival of
      patients with cholecystostomy versus no intervention (hazard ratio [HR] 1.13, P =
      0.256), although patients with cholecystectomy (with or without prior
      cholecystostomy) had improved survival (HR 0.29, P < 0.001; HR 0.56, P < 0.001).
      Results were similar among patients on the ventilator >96 h. CONCLUSIONS:
      Although cholecystostomy offered no survival benefit for patients with severe
      sepsis and shock, cholecystectomy offered improved survival compared with
      patients without surgical management. Cholecystostomy may not benefit the sickest
      patients in whom cholecystectomy may never be considered.

PMID- 24679698
TI  - Therapeutic potential of transgenic mesenchymal stem cells engineered to mediate
      anti-high mobility group box 1 activity: targeting of colon cancer.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are being developed as a new clinically
      relevant stem cell type to be recruited into and to repair injured tissue. A
      number of studies have focused on the therapeutic potential of MSCs by virtue of
      their immunomodulatory properties. Systemically administered MSCs can also
      migrate to sites of malignancies. Because of this latter phenomenon, we
      transfected human MSCs to secrete anti-high mobility group box (HMGB) 1 proteins.
      They were then injected into mice bearing human colon cancer to evaluate their
      efficacy as an antineoplastic agent. MATERIALS AND METHODS: The ABOX gene was
      used in this model, which encodes part of the HMGB1 protein and acts as an HMGB1
      antagonist. It was cotransduced by electroporation with a FLAG-tag to visualize
      the secreted ABOX protein, levels of which in supernatants from cultured
      transfected MSCs were quantified by immunofluorescence imaging using an anti-FLAG
      antibody. Antiangiogenic effects were evaluated in vitro using a novel optical
      assay device for the quantitative measurement of cellular chemotaxis assessing
      the velocity and direction of endothelial cell movement stimulated by supernatant
      from tumor cells. We found that ABOX proteins released from transfected MSCs
      suppressed migration in this assay. Finally, MSCs were injected subcutaneously
      into Nonobese diabetic/severe combined immunodeficiency mice bearing human colon
      cancer from a cell line, which secreted large amounts of HMGB1. Ten days after
      MSC injection, mice were sacrificed and tumors evaluated by immunohistochemistry.
      RESULTS: From 12 ho through 7 d after gene transfection, ABOX proteins secreted
      from MSCs could be detected by immunofluorescence and enzyme-linked immunosorbent
      assay. Quantitative measurement of cellular chemotaxis demonstrated that ABOX
      proteins secreted from transfected MSCs decreased the velocity and interfered
      with the direction of movement of vascular endothelial cells. Moreover, in an in
      vivo human colon cancer xenograft model, injection of anti-HMGB1-transfected MSCs
      resulted in a decreased tumor volume due to the antiangiogenic properties of the
      secreted ABOX proteins. CONCLUSIONS: MSC modified to secrete HMGB1 antagonist
      proteins have therapeutic antineoplastic potential. These findings may contribute
      to future novel targeting strategies using autologous bone marrow-derived cells
      as gene delivery vectors.

PMID- 24679699
TI  - The novel histone deacetylase inhibitor thailandepsin A inhibits anaplastic
      thyroid cancer growth.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) remains refractory to available
      surgical and medical interventions. Histone deacetylase (HDAC) inhibitors are an
      emerging targeted therapy with antiproliferative activity in a variety of thyroid
      cancer cell lines. Thailandepsin A (TDP-A) is a novel class I HDAC inhibitor
      whose efficacy remains largely unknown in ATC. Therefore, we aimed to
      characterize the effect of TDP-A on ATC. METHODS: Human-derived ATC cells were
      treated with TDP-A. IC50 was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) rapid colorimetric assay, and cell
      proliferation was measured by viable cell count. Molecular mechanisms of cell
      growth inhibition were investigated by Western blot analysis of canonical
      apoptosis markers, intrinsic and extrinsic apoptosis regulators, and cell cycle
      regulatory proteins. Cell cycle staging was determined with propidium iodide flow
      cytometry. RESULTS: TDP-A dose- and time-dependently reduced cell proliferation.
      Increased cleavage of the apoptosis markers Caspase-9, Caspase-3, and poly
      adenosine diphosphate ribose polymerase were observed with TDP-A treatment.
      Levels of the intrinsic apoptosis pathway proteins BAD, Bcl-XL, and BAX remained
      unchanged. Importantly, the extrinsic apoptosis activator cleaved Caspase-8
      increased dose-dependently, and the antiapoptotic proteins Survivin and Bcl-2
      decreased. Among the cell cycle regulatory proteins, levels of CDK inhibitors
      p21/WAF1 and p27/KIP increased. Flow cytometry showed that ATC cells were
      arrested in G2/M phase with diminished S phase after TDP-A treatment.
      CONCLUSIONS: TDP-A induces a notable dose- and time-dependent antiproliferative
      effect on ATC, which is mainly attributed to extrinsic apoptosis with concomitant
      cell cycle arrest. TDP-A therefore warrants further preclinical and clinical
      investigations.

PMID- 24679700
TI  - Discovery of previously undetected intellectual disability by psychological
      assessment: a study of consecutively referred child and adolescent psychiatric
      inpatients.
AB  - Intellectual disability is associated with an increased risk of behavioral
      disturbances and also complicates their treatment. Despite increases in the
      sophistication of medical detection of early risk for intellectual disability,
      there is remarkably little data about the detection of intellectual disability in
      cases referred for psychiatric treatment. In this study, we used a 10-year sample
      of 23,629 consecutive child and adolescent admissions (ages between 6 and 17) to
      inpatient psychiatric treatment. Eleven percent (n=2621) of these cases were
      referred for psychological assessment and were examined with a general measure of
      intellectual functioning (i.e., WISC-IV). Of these cases, 16% had Full Scale IQs
      below 70. Of the cases whose therapists then referred them for formal assessment
      of their adaptive functioning (i.e., ABAS-II) 81% were found to have composite
      scores below 70 as well. Only one of the cases whose Full Scale IQ was less than
      70 had a referral diagnosis of intellectual disability. Cases with previously
      undetected intellectual disability were found to be significantly more likely to
      have a diagnosis of a psychotic disorder and less likely to have a diagnosis of
      mood disorder than cases with IQs over 70. Disruptive behavior disorder diagnoses
      did not differ as a function of intellectual performance. These data suggest a
      high rate of undetected intellectual disability in cases with a psychiatric
      condition serious enough to require hospitalization and this raises the
      possibility that many such cases may be misdiagnosed, the basis of their problems
      may be misconceptualized, and they may be receiving treatments that do not take
      into account their intellectual level.

PMID- 24679701
TI  - Gait characteristics in children and adolescents with cerebral palsy assessed
      with a trunk-worn accelerometer.
AB  - This study aimed to investigate gait characteristics reflecting balance and
      progression in children and adolescents with cerebral palsy (CP) compared with
      typically developing (TD) children. Gait characteristics variables representing
      aspects of balance were trunk acceleration, interstride regularity and asymmetry
      of accelerations while gait characteristics representing progression were gait
      speed, cadence, step time and step length. Children in the age range 5-18 years
      (mean age 11.1 years) with spastic CP (n=41) and a gross motor function
      corresponding to GMFCS I-III and children with TD (n=29) were included. The
      children walked back and forth along a 5m pathway with a tri-axial accelerometer
      worn on the lower back to allow assessment of their gait characteristics. Data
      were recorded along the anterioposterior (AP), mediolateral (ML), and vertical
      (V) axes. To assess the magnitude of potential differences in gait
      characteristics, standard deviation scores were calculated, using TD children as
      reference. Gait parameters related to balance, such as AP, ML, and V
      accelerations, were higher in the children with CP (z-scores between 0.4 and 0.7)
      and increased with increasing GMFCS levels. The differences in accelerations in
      the AP and V directions increased between children with CP and TD children with
      increasing speed. Also asymmetry in trunk accelerations differed significantly
      between the two groups in all three directions (z-scores between 0.8 and 1.8
      higher in the CP group), while interstride regularity differed only slightly
      between children with CP and TD children, and only in the AP direction. Gait
      characteristics also differed between children with the spastic subtypes
      unilateral and bilateral CP, for accelerations and asymmetry in the AP and ML
      directions. Our results showed significant differences in gait characteristics
      between children with CP and TD children. The differences may be more related to
      balance than progression, and these problems seem to rise with increasing gross
      motor impairment and speed.

PMID- 24679702
TI  - Synthesis, antibiotic activity and structure-activity relationship study of some
      3-enaminetetramic acids.
AB  - The synthesis and evaluation of 3-enaminetetramic acids as antibacterial agents
      is reported; contrary to the analogous 3-acyltetramic acids, the enaminetetramic
      acid class of compound exhibits modest antibacterial activity against a limited
      spectrum of organisms, and even that activity is strongly dependent on the
      identity of the tetramate ring substituents. Moreover, these compounds appear to
      have a different mode of action to the analogous 3-acyltetramic acids, and appear
      to offer more limited opportunity for further elaboration in drug discovery. 

PMID- 24679703
TI  - Design, synthesis and evaluation of 1,2,3-triazole-adamantylacetamide hybrids as
      potent inhibitors of Mycobacterium tuberculosis.
AB  - A series of novel 1,2,3-triazole-adamantylacetamide hybrids 5a-u, designed by
      combining bioactive fragments from antitubercular I-A09 and substituted adamantyl
      urea, were synthesized using copper catalyzed click chemistry. N-(1-Adamantyl)-2
      azido acetamide 3 prepared from 1-adamantylamine was reacted with a series of
      alkyl/aryl acetylenes in the presence of copper sulfate and sodium ascorbate to
      give new analogues 5a-u in very good yields. Evaluation of all new compounds for
      in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv
      (ATCC27294), resulted N-(1-adamantan-1-yl)-2-(4-(phenanthren-2-yl)-1H-1,2,3
      triazol-1-yl)acetamide (5t) as most promising lead MIC: 3.12 MUg/mL) with
      selectivity index >15.

PMID- 24679705
TI  - Can proteomics fill the gap between genomics and phenotypes?

PMID- 24679704
TI  - Applications and cost benefits of sexed semen in pasture-based dairy production
      systems.
AB  - Sexed semen technology is now commercially available in many countries around the
      world, and is primarily used in dairy cattle breeding. Sperm are sorted by flow
      cytometry on the basis of a 4% difference in DNA content between sperm containing
      X and Y chromosomes. Despite reliably producing a 90% gender bias, the fertility
      of the sexed semen product is compromised compared with conventional semen. The
      negative implications of the reduced fertility of sexed semen are amplified in
      seasonal systems of dairy production, as the importance of fertility is greater
      in these systems compared with year-round calving systems. A review of the
      literature indicates that conception rates (CR) to 1st service with frozen-thawed
      sexed semen are ~75% to 80% of those achieved with conventional frozen-thawed
      semen. Preliminary results from a large-scale field trial carried out in Ireland
      in 2013 suggest that significant improvements in the performance of sexed semen
      have been made, with CR of 87% of those achieved with conventional semen. The
      improved fertility of a sexed semen product that delivers a 90% gender bias has
      considerable implications for the future of breeding management in pasture-based
      dairy production systems. Sexed semen may facilitate faster, more profitable
      dairy herd expansion by increasing the number of dairy heifer replacements born.
      Biosecurity can be improved by maintaining a closed herd during the period of
      herd expansion. In a non-expansion scenario, sexed semen may be used to increase
      the value of beef output from the dairy herd. The replacement heifer requirements
      for a herd could be met by using sexed semen in the 1st 3 weeks of the breeding
      season, with the remaining animals bred to beef sires, increasing the sale value
      over that of a dairy bull calf. Alternatively, very short gestation sires could
      be used to shorten the calving interval. Market prices have a considerable effect
      on the economics of sexed semen use, and widespread use of sexed semen should be
      restricted to well managed herds that already achieve acceptable herd fertility
      performance. 

PMID- 24679706
TI  - [Progressive prosopagnosia associated with right temporal atrophy in a patient
      with hereditary dementia].

PMID- 24679707
TI  - Allergologia et Immunopathologia: a second step forward.

PMID- 24679708
TI  - A simple field method to identify foot strike pattern during running.
AB  - Identifying foot strike patterns in running is an important issue for sport
      clinicians, coaches and footwear industrials. Current methods allow the
      monitoring of either many steps in laboratory conditions or only a few steps in
      the field. Because measuring running biomechanics during actual practice is
      critical, our purpose is to validate a method aiming at identifying foot strike
      patterns during continuous field measurements. Based on heel and metatarsal
      accelerations, this method requires two uniaxial accelerometers. The time between
      heel and metatarsal acceleration peaks (THM) was compared to the foot strike
      angle in the sagittal plane (alphafoot) obtained by 2D video analysis for various
      conditions of speed, slope, footwear, foot strike and state of fatigue.
      Acceleration and kinematic measurements were performed at 1000Hz and 120Hz,
      respectively, during 2-min treadmill running bouts. Significant correlations were
      observed between THM and alphafoot for 14 out of 15 conditions. The overall
      correlation coefficient was r=0.916 (P<0.0001, n=288). The THM method is thus
      highly reliable for a wide range of speeds and slopes, and for all types of foot
      strike except for extreme forefoot strike during which the heel rarely or never
      strikes the ground, and for different footwears and states of fatigue. We
      proposed a classification based on THM: FFS<-5.49ms<MFS<15.2ms<RFS. With only a
      few precautions being necessary to ensure appropriate use of this method, it is
      reliable for distinguishing rearfoot and non-rearfoot strikers in situ. 

PMID- 24679709
TI  - The contribution of body weight distribution and center of pressure location in
      the control of mediolateral stance.
AB  - The study investigated the mediolateral control of upright stance in 16 healthy,
      young adults. The model analyzed the body weight distribution and center of
      pressure location mechanisms under three stance width conditions (feet close,
      under standard condition, and apart). Our first objective was to discuss some
      methodological requirements to investigate the contribution of both mechanisms by
      means of two platforms. It is proposed that both the amplitude contribution (in
      variability analyses) and active contribution (in cross-correlation analyses)
      need to be studied distinctively. These analyses may be concerned with the
      strength and the degree of active contributions, respectively. Based on this
      theoretical proposition, we expected and found that the amplitude contribution of
      both mechanisms was higher and lower in wide and narrow stances compared with
      that in the standard stance, respectively. Indeed, the closer the two reaction
      forces, the lower their mechanical contribution. As expected, the active
      contribution of both mechanisms was significantly lower and higher in wide and
      narrow stances, respectively. Indeed, the further the feet apart, the less active
      both mechanisms needed to be to control mediolateral stance. Overall, only the
      center of pressure location mechanism really changed its significant contribution
      to control mediolateral stance under the three conditions. The result is
      important because this mechanism is known to be secondary, weaker than the body
      weight distribution mechanism to control mediolateral stance. In practical terms,
      these findings may explain why the mediolateral variability of center of pressure
      displacement was significantly higher in narrow stance but not lower in wide
      stance. 

PMID- 24679711
TI  - Passive aortic counterpulsation: biomechanical rationale and bench validation.
AB  - Aortic counterpulsation (IABP) consists in an ECG-controlled forced deflation and
      inflation of a balloon positioned in the aorta. The device is designed to
      decrease the ventricular afterload during systole and to increase the coronary
      driving pressure during diastole. In biomechanical terms, the IABP improves the
      mechanical matching between the pump and the load, facilitating the transfer of
      ventricular energy. This paper describes a completely passive aortic
      counterpulsation solution, with an intra-aortic balloon without a pumping system,
      designed to improve the mechanical matching between the ventricle and the artery
      at very low cost and complexity. The only requirement is an external reservoir to
      amplify the balloon pulsations due to physiologic arterial pressure pulse. Using
      a cardiovascular simulator and changing the reservoir pressure, a systolic not
      negligible (7.8ml) gas volume exchange between the intra-aortic balloon and the
      reservoir was measured. The same cardiovascular simulator was used to demonstrate
      an increase in stroke volume in three conditions of progressive ventricular
      failure, by detecting a change in systolic and diastolic arterial pressures and
      stroke volume (SV). The maximal arterial pressure always decreased and the
      diastolic pressure increased. The SV increased up to 7.8%, demonstrating an
      arterial elastance reduction and better ventricular-aortic mechanical matching
      and energy transfer. 

PMID- 24679710
TI  - Dynamic stability of individuals with transtibial amputation walking in
      destabilizing environments.
AB  - Lower limb amputation substantially disrupts motor and proprioceptive function.
      People with lower limb amputation experience considerable impairments in walking
      ability, including increased fall risk. Understanding the biomechanical aspects
      of the gait of these patients is crucial in improving their gait function and
      their quality of life. In the present study, 9 persons with unilateral
      transtibial amputation and 13 able-bodied controls walked on a large treadmill in
      a Computer Assisted Rehabilitation Environment (CAREN). While walking, subjects
      were either not perturbed, or were perturbed either by continuous mediolateral
      platform movements or by continuous mediolateral movements of the visual scene.
      Means and standard deviations of both step lengths and step widths increased
      significantly during both perturbation conditions (all p<0.001) for both groups.
      Measures of variability, local and orbital dynamic stability of trunk movements
      likewise exhibited large and highly significant increases during both
      perturbation conditions (all p<0.001) for both groups. Patients with amputation
      exhibited greater step width variability (p=0.01) and greater trunk movement
      variability (p=0.04) during platform perturbations, but did not exhibit greater
      local or orbital instability than healthy controls for either perturbation
      conditions. Our findings suggest that, in the absence of other co-morbidities,
      patients with unilateral transtibial amputation appear to retain sufficient
      sensory and motor function to maintain overall upper body stability during
      walking, even when substantially challenged. Additionally, these patients did not
      appear to rely more heavily on visual feedback to maintain trunk stability during
      these walking tasks. 

PMID- 24679712
TI  - Use of audio biofeedback to reduce tibial impact accelerations during running.
AB  - Visual biofeedback of tibial peak positive acceleration (PPA) during running has
      been used successfully as a method of gait retraining to reduce PPAs. Audio
      biofeedback generated from PPA may present a novel, portable alternative. The
      purpose of this study was to investigate the feasibility of using PPA-generated
      audio biofeedback to reduce PPAs while running. Nine runners were fitted with a
      wireless accelerometer on their left tibia. PPAs were recorded and a custom
      LabVIEW program was used to emit a single beep once the PPA reached a preset
      threshold. The numerical difference between this threshold and peak PPA during
      running was scaled to the pitch of the beep, such that a foot strike with greater
      PPA would result in a beep with higher pitch. Subjects were then instructed to
      (1) run without any beeps, and/or (2) keep the pitch of the beep as low as
      possible. Subjects participated in a single testing session that included a five
      minute warm-up and two rounds of biofeedback, which consisted of five minutes of
      running with biofeedback followed by five minutes of running without biofeedback.
      Subjects were able to significantly reduce PPAs during exposure to audio
      biofeedback. In addition, two rounds of biofeedback were sufficient for subjects
      to retain a reduction in PPAs without biofeedback. PPA-generated audio
      biofeedback therefore appears to be a feasible method of gait retraining to
      reduce PPAs in runners. 

PMID- 24679713
TI  - SHIP1 and the negative control of mast cell/basophil activation by supra-optimal
      antigen concentrations.
AB  - IgE-mediated, antigen-triggered activation of mast cells and basophils often
      results in bell-shaped dose-response curves for the release of various pro
      inflammatory mediators. The degree of suppression of mediator release observed
      following supra-optimal stimulation varies widely for different allergens as well
      as for different experimental agents that cause crosslinking of high-affinity IgE
      receptors (FcERI) on these cells. While the reasons for these differences have
      not yet been resolved it has become increasingly apparent that supra-optimal
      stimulation in many cases causes a shift in the balance of stimulatory and
      inhibitory signal transduction mechanisms arising from FcERI triggering. In
      particular, the lipid phosphatase SHIP1 has been shown to be centrally involved
      in explaining the bell-shaped phenomena in both mast cells and basophils in
      different species and appears to play a fundamental role in limiting the IgE
      responsiveness of these allergic effector cells. Elucidating the nature of this
      inhibitory signaling pathway may provide crucial knowledge in order to optimize
      desensitization strategies in the treatment of allergic diseases. 

PMID- 24679714
TI  - Gardens that take care of us.
AB  - After a long period of absence, hospital and care-facility gardens are making a
      comeback. But these new gardens are not just ornamental. They aim to improve
      wellbeing. Some are even designed to change the outcome of disease-including
      neurological disease. Adrian Burton investigates.

PMID- 24679715
TI  - Molecular detection of canine parvovirus in flies (Diptera) at open and closed
      canine facilities in the eastern United States.
AB  - More than thirty years have passed since canine parvovirus (CPV) emerged as a
      significant pathogen and it continues to pose a severe threat to world canine
      populations. Published information suggests that flies (Diptera) may play a role
      in spreading this virus; however, they have not been studied extensively and the
      degree of their involvement is not known. This investigation was directed toward
      evaluating the vector capacity of such flies and determining their potential role
      in the transmission and ecology of CPV. Molecular diagnostic methods were used in
      this cross-sectional study to detect the presence of CPV in flies trapped at
      thirty-eight canine facilities. The flies involved were identified as belonging
      to the house fly (Mucidae), flesh fly (Sarcophagidae) and blow/bottle fly
      (Calliphoridae) families. A primary surveillance location (PSL) was established
      at a canine facility in south-central South Carolina, USA, to identify fly-virus
      interaction within the canine facility environment. Flies trapped at this
      location were pooled monthly and assayed for CPV using polymerase chain reaction
      (PCR) methods. These insects were found to be positive for CPV every month from
      February through the end of November 2011. Fly vector behavior and seasonality
      were documented and potential environmental risk factors were evaluated.
      Statistical analyses were conducted to compare the mean numbers of each of the
      three fly families captured, and after determining fly CPV status (positive or
      negative), it was determined whether there were significant relationships between
      numbers of flies captured, seasonal numbers of CPV cases, temperature and
      rainfall. Flies were also sampled at thirty-seven additional canine facility
      surveillance locations (ASL) and at four non-canine animal industry locations
      serving as negative field controls. Canine facility risk factors were identified
      and evaluated. Statistical analyses were conducted on the number of CPV cases
      reported within the past year to determine the correlation of fly CPV status
      (positive or negative) for each facility, facility design (open or closed), mean
      number of dogs present monthly and number of flies captured. Significant
      differences occurred between fly CPV positive vs. negative sites with regard to
      their CPV case numbers, fly numbers captured, and number of dogs present. At the
      ASL, a statistically significant relationship was found between PCR-determined
      fly CPV status (positive or negative) and facility design (open vs. closed). Open
      facility designs were likely to have more CPV outbreaks and more likely to have
      flies testing positive for CPV DNA. 

PMID- 24679716
TI  - Simulation modelling of a hypothetical introduction of foot-and-mouth disease
      into Alberta.
AB  - This study describes the use of simulation modelling to evaluate the predicted
      benefits of an effective livestock traceability system in responding to a
      hypothetical introduction of foot-and-mouth disease (FMD) in to the province of
      Alberta, Canada, and whether or not the implementation of emergency ring
      vaccination in addition to a standard stamping-out (SO) strategy would lead to
      smaller and shorter epidemics. Three introduction scenarios were defined, with
      the primary case in either an intensive beef feedlot operation, an extensive cow
      calf operation or in a swine operation. Disease spread was simulated using, three
      levels of tracing effectiveness, five types of vaccination zone, three different
      vaccination start times, three lengths of vaccination campaigns, two levels of
      culling resource and using FMD strains with two different virulence levels. Using
      standard SO procedures (without vaccination), improving traceability
      effectiveness from a level whereby only 65% of movements were traced within 5-7
      days, to a capability whereby all movements were traced within 1 day, led to a
      reduction in the number of infected premises (IPs) between 18.7 and 64.5%, an
      average saving of CAN$29,000,000 in livestock compensation costs alone, and a
      reduction in the length of epidemics ranging from 1 to 22 days. The
      implementation of emergency vaccination also led to a reduction in the number of
      IPs and a shortening of epidemics. The effects were more pronounced when the
      higher virulence settings were used, with a predicted reduction in IPs of 16.6
      68.7% (mean=48.6%) and epidemics shortened by up to 37 days. Multi-variable
      analyses showed these effects were highly significant, after accounting for the
      incursion location, virulence of virus and time of first detection. The results
      clearly demonstrated the benefits of having effective traceability systems with
      rapid query and reporting functionality. The results also supported the value of
      early vaccination as an adjunct to SO in reducing the number of IPs and
      shortening the length of the epidemics. The most effective vaccination strategy
      involved a 3 km or larger suppressive vaccination zone around all IPs, begun as
      soon as practicable after first detection, and which continued until the last IP
      was detected.

PMID- 24679717
TI  - The importance of recognizing pellagra (niacin deficiency) as it still occurs.

PMID- 24679718
TI  - Drug-resistance--a challenge for tuberculosis control in the European Union and
      European Economic Area.

PMID- 24679719
TI  - Molecular surveillance of multi- and extensively drug-resistant tuberculosis
      transmission in the European Union from 2003 to 2011.
AB  - The European Centre for Disease Prevention and Control (ECDC) initiated a project
      on the molecular surveillance of multi- and extensively drug-resistant
      tuberculosis (MDR-/XDR-TB) transmission in the European Union (EU) in the period
      from 2009 to 2011. In total, 2,092 variable number of tandem repeat (VNTR)
      patterns of MDR-/XDR-TB Mycobacterium tuberculosis isolates were collected,
      originating from 24 different countries in the period 2003 to 2011. Of the
      collected VNTR patterns, 45% (n=941) could be assigned to one of the 79 European
      multiple-country molecular fingerprint clusters and 50% of those (n=470) belonged
      to one extremely large cluster caused by Beijing strains of one genotype. We
      conclude that international transmission of MDR-/XDR-TB plays an important role
      in the EU, especially in the eastern part, and is significantly related to the
      spread of one strain or clone of the Beijing genotype. Implementation of
      international cluster investigation in EU countries should reveal underlying
      factors of transmission, and show how TB control can be improved regarding case
      finding, contact tracing, infection control and treatment in order to prevent
      further spread of MDR-/XDR-TB in the EU.

PMID- 24679720
TI  - Extent and origin of resistance to antituberculosis drugs in the Netherlands,
      1993 to 2011.
AB  - The elimination of tuberculosis (TB) is threatened by an apparent increase in the
      level of resistance in Mycobacterium tuberculosis. In the Netherlands, where the
      majority of TB patients are migrants, resistance may also be increasing. We
      conducted a retrospective study, using 18,294 M. tuberculosis isolates from TB
      cases notified between 1993 and 2011. We investigated the trends in
      antituberculosis drug resistance, focusing on the country of birth of the
      patients and whether resistance had developed during treatment or was the result
      of transmission of resistant M. tuberculosis strains. For both scenarios, we
      determined whether this had happened in or outside the Netherlands.
      Antituberculosis drug resistance was found in 13% of all cases analysed and
      showed an increasing trend among patients who had been born in the Netherlands
      (p<0.001) and a decreasing trend among foreign-born (p=0.02) over the study
      period. Since 2005, the proportion of M. tuberculosis resistant strains among all
      strains tested has increased in both groups (p=0.03 and p=0.01, respectively).
      Overall, we found a significantly increasing trend when excluding streptomycin
      resistance (p<0.001). The trend was most markedly increased for isoniazid
      resistance (p = 0.01). Although resistance was mainly due to transmission of
      resistant strains, mostly outside the Netherlands or before 1993 (when DNA
      fingerprinting was not systematically performed), in some cases (n=45),
      resistance was acquired in the Netherlands. We conclude that antituberculosis
      drug resistance is increasing in the Netherlands, mostly related to migration
      from high TB-incidence countries, but also to domestic acquisition.

PMID- 24679721
TI  - Transmission of multidrug-resistant tuberculosis in a low-incidence setting,
      Switzerland, 2006 to 2012.
AB  - The goal of the present study was to examine the transmission dynamics of
      multidrug-resistant tuberculosis (MDR-TB) in Switzerland. Between 2006 and 2012,
      a total of 49 MDR-TB cases were reported to the Swiss Federal Office of Public
      Health, 46 of which were of foreign origin. All 49 initial strains were evaluated
      by molecular epidemiologic methods at the Swiss National Reference Centre for
      Mycobacteria. In 43 strains, unique DNA fingerprint patterns were identified.
      Twelve strains were grouped into six clusters. Data from contact tracing suggest
      likely in-country transmission in four clusters, mostly among close contacts. In
      the remaining two clusters, no contact tracing data were available, but the
      identified genotypes were known to be prevalent in the countries of origin of the
      patients, suggesting the possibility that the infection was acquired there. While
      most MDR-TB cases are imported to Switzerland, at least four of the 49 MDR-TB
      cases were due to transmission within the country. The imported cases, however,
      did not lead to secondary cases outside the circles of close contacts. The
      results also indicate that prevention of MDR-TB transmission among immigrants may
      require closer monitoring.

PMID- 24679722
TI  - Geographical heterogeneity of multidrug-resistant tuberculosis in Georgia,
      January 2009 to June 2011.
AB  - In 2011, Georgia, in the Caucasus, reported that 11% of new and 32% of previously
      treated tuberculosis (TB) cases nationally had multidrug-resistant TB (MDR-TB).
      To help understand the mechanisms driving these high risks of drug-resistance and
      plan for targeted interventions, we identified geographical variability in the
      MDR-TB burden in Georgia and patient-level MDR-TB risk factors. We used routinely
      collected surveillance data on notified TB cases to estimate the MDR-TB
      incidence/100,000 people and the percentage of TB cases with MDR-TB for each of
      65 districts and regression modelling to identify patient-level MDR-TB risk
      factors. 1,795 MDR-TB cases were reported (January 2009-June 2011); the
      nationwide notified MDR-TB incidence was 16.2/100,000 but far higher
      (837/100,000) in the penitentiary system. We found substantial geographical
      heterogeneity between districts in the average annual MDR-TB incidence/100,000
      (range: 0.0-5.0 among new and 0.0-18.9 among previously treated TB cases) and the
      percentage of TB cases with MDR-TB (range: 0.0%-33.3% among new and 0.0%-75.0%
      among previously treated TB cases). Among treatment-naive individuals, those in
      cities had greater MDR-TB risk than those in rural areas (increased odds: 43%;
      95% confidence interval: 20%-72%). These results suggest that interventions for
      interrupting MDR-TB transmission are urgently needed in prisons and urban areas.

PMID- 24679724
TI  - ECDC and WHO/Europe joint report on tuberculosis surveillance and monitoring in
      Europe.

PMID- 24679723
TI  - Laboratory diagnosis of paediatric tuberculosis in the European Union/European
      Economic Area: analysis of routine laboratory data, 2007 to 2011.
AB  - Laboratory confirmation of paediatric tuberculosis (TB) is frequently lacking. We
      reviewed the range of routine laboratory tests and their performance in different
      biological samples used to diagnose active TB in children. A questionnaire-based
      survey was conducted among the European Reference Laboratory Network for TB
      followed by collection of routine laboratory data on 10,549 paediatric samples
      tested in 2007 to 2011 at six reference laboratories (in Croatia, Germany, Italy,
      Latvia, Lithuania and the United Kingdom (UK)). The questionnaire showed that all
      laboratories used rapid assays. Non-respiratory samples were collected more often
      in Germany (135/275, 49.1%) and the UK (490/2,140, 22.9%) compared with Croatia
      (138/2,792, 4.9%), Latvia (222/2,401, 9.2%) and Lithuania (76/1,549, 4.9%).
      Overall laboratory positivity rates (isolation of Mycobacterium tuberculosis
      complex and/or identification of its nucleic acids in a sample) were higher in
      lymph node and gastric aspirate samples (14/203 (6.9%) and 43/1,231 (3.5%)) than
      in sputum samples (89/4,684 (1.9%)). Pooled sensitivity, specificity, positive
      and negative predictive values and accuracy of molecular assays assessed against
      solid or liquid culture were 79.2%, 93.6%, 67.1%, 96.5% and 91.6%, respectively.
      A more intensive approach in obtaining gastric aspirate and non-respiratory
      samples may increase laboratory confirmation of paediatric TB. Major effort is
      needed in optimisation and validation of molecular tests in these samples.

PMID- 24679727
TI  - Herniated disc extruded in the retroperitoneum.

PMID- 24679730
TI  - Stress and allergic diseases--still under recognized and undertreated.

PMID- 24679731
TI  - Integrative approach to allergy and asthma using complementary and alternative
      medicine.

PMID- 24679732
TI  - A 37-year-old man referred for assistance with persistent asthma, atopic
      dermatitis, and chronic conjunctivitis.

PMID- 24679729
TI  - Erlotinib versus radiation therapy for brain metastases in patients with EGFR
      mutant lung adenocarcinoma.
AB  - PURPOSE/OBJECTIVES: Radiation therapy (RT) is the principal modality in the
      treatment of patients with brain metastases (BM). However, given the activity of
      EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain
      whether upfront brain RT is necessary for patients with EGFR-mutant lung
      adenocarcinoma with BM. METHODS AND MATERIALS: Patients with EGFR-mutant lung
      adenocarcinoma and newly diagnosed BM were identified. RESULTS: 222 patients were
      identified. Exclusion criteria included prior erlotinib use, presence of a de
      novo erlotinib resistance mutation, or incomplete data. Of the remaining 110
      patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15
      with stereotactic radiosurgery (SRS). The median overall survival (OS) for the
      whole cohort was 33 months. There was no significant difference in OS between the
      WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients
      treated with SRS had a longer OS than did those in the erlotinib group (median,
      64 months; P=.004). The median time to intracranial progression was 17 months.
      There was a longer time to intracranial progression in patients who received WBRT
      than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04).
      Patients in the erlotinib or SRS group were more likely to experience
      intracranial failure as a component of first failure, whereas WBRT patients were
      more likely to experience failure outside the brain (P=.004). CONCLUSIONS: The
      survival of patients with EGFR-mutant adenocarcinoma with BM is notably long,
      whether they receive upfront erlotinib or brain RT. We observed longer
      intracranial control with WBRT, even though the WBRT patients had a higher burden
      of intracranial disease. Despite the equivalent survival between the WBRT and
      erlotinib group, this study underscores the role of WBRT in producing durable
      intracranial control in comparison with a targeted biologic agent with known
      central nervous system activity.

PMID- 24679733
TI  - Diagnosis and treatment of nasal and ocular allergies: the Allergies,
      Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys.
AB  - BACKGROUND: Allergic rhinoconjunctivitis (ARC) is managed by a number of health
      care professional specialties, whose practice styles may vary. OBJECTIVE: To
      survey patients and health care professionals about the diagnosis and treatment
      of ARC. METHODS: The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS)
      surveys were telephone surveys of randomly selected patients and health care
      professionals in the United States in 2012. Participants were 2,765 people ever
      diagnosed as having nasal and/or ocular allergies and 500 practitioners in 7
      specialties who were treating ARC. RESULTS: Adult respondents to the patient
      survey reported that their allergies had been diagnosed most often by physicians
      in family practice (46%) rather than by allergists/immunologists (17%) or
      otolaryngologists (11%). Children's allergies had been diagnosed most often by
      pediatricians (41%) and family practitioners (22%). Most respondents with
      conditions diagnosed by an allergist/immunologist (94.9%) or otolaryngologist
      (62.7%) had been given an allergy test, but the test was not given to most
      patients with conditions diagnosed by family practitioners (61.3%) or
      pediatricians (64.9%). Most patients (75.8%) were treating their allergies with
      over-the-counter medications, and 53.5% were taking prescription medications.
      Allergen immunotherapy was being used by 33% (adult) or 28% (child) patients of
      allergist/immunologists, 25% (adult) or 24% (child) patients of
      otolaryngologists, and 8% and 10% of patients of family practitioners and
      pediatricians, respectively. CONCLUSION: Most patients took nonprescription
      medications for their allergy symptoms or were treated by general practitioners,
      who did not use allergy testing when diagnosing ARC. Most patients seen by
      allergist/immunologists and otolaryngologists were evaluated with allergy tests,
      and most allergen immunotherapy was provided by allergy specialists.

PMID- 24679735
TI  - Allergen of the month--Western dock.

PMID- 24679734
TI  - Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil
      predominant airway inflammation in a ragweed sensitized murine asthma model.
AB  - BACKGROUND: Neutrophil-predominant asthma is less responsive to steroids and
      associated with poorer disease control. The effects of Antiasthma Simplified
      Herbal Medicine Intervention (ASHMI), a traditional Chinese medicine formula
      reported to be efficacious in asthmatic patients and murine asthma models, on
      neutrophil predominant asthma are unknown. OBJECTIVE: To determine the effects of
      standard ASHMI and refined formula ASHMI (ASHMI(II)) in a neutrophil-predominant
      murine model of ragweed (RW) asthma and explore underlying mechanisms. METHODS:
      BALB/c mice were systemically sensitized, intranasally challenged with RW
      extract, and orally treated with ASHMI, ASHMI(II), or vehicle (water). In a
      separate experiment, some RW sensitized mice were treated with dexamethasone
      before challenge. After RW challenge, airway hyperreactivity (AHR), total and
      differential bronchoalveolar lavage fluid leukocyte counts, lung histologic
      features, and bronchoalveolar lavage fluid cytokine and chemokine levels were
      assessed. RW stimulation of the murine macrophage cell line RAW264.7 was used to
      determine effects of ASHMI active compound ganoderic acid C1 (GAC1) on tumor
      necrosis factor alpha (TNF-alpha) production and regulation of phosphorylated
      IkappaB and histone deacetylase 2 (HDAC2) levels. RESULTS: ASHMI and ASHMI(II)
      markedly reduced AHR, mucous production, neutrophilic inflammation, and TNF
      alpha, interleukin 8, and interleukin 17 levels and decreased eosinophilic
      inflammation and TH2 responses in vivo (P < .01-.001 for all). GAC1 inhibited TNF
      alpha production in RW-stimulated RAW264.7 cells in association with suppression
      of phosphorylated IkappaB and increased HDAC2 expression. Dexamethasone failed to
      reduce AHR and neutrophilic inflammation. CONCLUSION: ASHMI treatment was
      efficacious in a murine model of neutrophil-predominant asthma via modulation of
      innate chemokines, TH2 responses, nuclear factor-kappaB, and HDAC2. ASHMI, and/or
      its constituent GAC1, may be a valuable option for treating neutrophil
      predominant asthma.

PMID- 24679736
TI  - Tremor retrainment as therapeutic strategy in psychogenic (functional) tremor.
AB  - BACKGROUND: Entrainment, the change or elimination of tremor as patients perform
      a voluntary rhythmical movement by the unaffected limb, is a key diagnostic
      hallmark of psychogenic tremor. OBJECTIVE: To evaluate the feasibility of using
      entrainment as a bedside therapeutic strategy ('retrainment') in patients with
      psychogenic tremor. METHODS: Ten patients with psychogenic tremor (5 women, mean
      age, 53.6 +/- 12.8 years; mean disease duration 4.3 +/- 2.7 years) were asked to
      participate in a pilot proof-of-concept study aimed at "retraining" their tremor
      frequency. Retrainment was facilitated by tactile and auditory external cueing
      and real-time visual feedback on a computer screen. The primary outcome measure
      was the Tremor subscale of the Rating Scale for Psychogenic Movement Disorders.
      RESULTS: Tremor improved from 22.2 +/- 13.39 to 4.3 +/- 5.51 (p = 0.0019) at the
      end of retrainment. The benefits were maintained for at least 1 week and up to 6
      months in 6 patients, with relapses occurring in 4 patients between 2 weeks and 6
      months. Three subjects achieved tremor freedom. CONCLUSIONS: Tremor retrainment
      may be an effective short-term treatment strategy in psychogenic tremor. Although
      blinded evaluations are not feasible, future studies should examine the long-term
      benefits of tremor retrainment as adjunctive to psychotherapy or specialized
      physical therapy.

PMID- 24679737
TI  - Severity of depression and anxiety are predictors of response to antidepressant
      treatment in Parkinson's disease.
AB  - BACKGROUND: Antidepressants have appeared to be more effective than placebo
      treatment in treating depressive syndromes in patients with Parkinson's disease
      (PD). OBJECTIVE: To identify factors that predict improvement in depressive
      symptoms during antidepressant treatment in depressed PD patients. METHODS: A
      secondary analysis was performed on the dataset of the Randomized Placebo
      controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received
      active treatment with either paroxetine or venlafaxine extended release (XR), and
      39 patients received placebo treatment. Backward stepwise regression analyses
      were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24)
      score between assessments at baseline and week 12 as the main outcome measure,
      and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale
      section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the
      Clinical Anxiety Scale (CAS) as independent variables. RESULTS: In both the
      active treatment and placebo groups, higher baseline HAMD-24 score and lower
      UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher
      anxiety scores predicted less response in the active treatment group. Higher MMSE
      scores predicted greater response only in the placebo-treated group. Sex and age
      were no predictors of response. CONCLUSIONS: Higher pre-treatment depression
      scores and lower pre-treatment anxiety scores are the two most important
      predictors for improvement during antidepressant treatment in depressed PD
      patients, which is in line with those found in treatment studies of depressed non
      PD patients. Furthermore, our results indicate the requirement for different or
      more intensive treatment for depressed PD patients with more severe anxiety
      symptoms.

PMID- 24679738
TI  - Clinical evaluation of high mobility group box 1 protein in Legionella
      pneumophila pneumonia.
AB  - High mobility group box 1 (HMGB-1) protein is involved in acute lung injury due
      to various etiologies. We evaluated HMGB-1 levels in sera and bronchoalveolar
      fluids in patients with pneumonia caused by Legionella pneumophila. Levels of
      HMGB-1 in the sera of patients with L. pneumophila pneumonia (32 cases) and
      control subjects (24 cases) were determined. Serum HMGB-1 levels in Legionella
      pneumonia were similar to those of the control subjects. No significant
      correlation between HMGB-1 levels and other biomarkers and the outcome of cases
      was observed. In contrast, HMGB-1 levels, as well as interferon-gamma, in
      bronchoalveolar (BA) fluids from severe L. pneumophila pneumonia (7 cases) were
      significantly higher than those in the sera of identical patients. HMGB-1 levels
      in BA fluids were relatively higher in pneumonia cases with ALI than those
      without ALI. Our findings suggest that intra-pulmonary HMGB-1 may be involved in
      the pathophysiology of pneumonia caused by L. pneumophila. 

PMID- 24679739
TI  - Detection of coronary artery disease using coronary flow velocity reserve by
      transthoracic Doppler echocardiography versus multidetector computed tomography
      coronary angiography: influence of calcium score.
AB  - BACKGROUND: There have been no clinical data specifying the degree of calcium
      deposition at which coronary flow velocity reserve (CFVR) measurement using
      transthoracic Doppler echocardiography surpasses 320-row multidetector computed
      tomographic coronary angiography (CTCA) in detecting obstructive coronary artery
      disease. METHODS: One hundred seventy patients who underwent invasive coronary
      angiography, transthoracic Doppler echocardiography, and CTCA were prospectively
      enrolled. Coronary artery stenosis was defined as percentage diameter stenosis >=
      50% on invasive coronary angiography. CFVR < 2.0 and narrowing >= 50% measured
      with CTCA were the thresholds indicating the presence of coronary artery
      stenosis. The degree of coronary artery calcification was also assessed using the
      Agatston calcium score method by computed tomography. RESULTS: The majority of
      patients (89%) were classified as having either high or intermediate pretest
      probability of coronary artery disease. Significant coronary artery stenoses by
      invasive coronary angiography were found in 71 patients and 104 vessels. Although
      the overall diagnostic performance of CTCA was comparable with that of CFVR
      measurement for detecting coronary artery stenosis, only the diagnostic
      performance of CTCA was negatively affected by the extent of a patient's coronary
      artery calcification. Receiver operating characteristic curve analysis indicated
      that only CFVR measurement is diagnostically accurate when calcium scores are
      >319 in the patient-based assessment, 189 for the left anterior descending
      coronary artery, 98 for the left circumflex coronary artery and 282 for the right
      coronary artery. CONCLUSIONS: Transthoracic Doppler echocardiography and 320-row
      multidetector CTCA successfully diagnosed significant coronary artery stenosis
      with high feasibility and accuracy. However, only the diagnostic performance of
      CTCA was negatively affected by the extent of a patient's coronary artery
      calcification, and therefore the diagnostic performance of CFVR measurement for
      detecting coronary artery stenosis surpassed that of CTCA when the calcium score
      exceeded specified cutoff values.

PMID- 24679740
TI  - Right ventricular global longitudinal strain provides prognostic value
      incremental to left ventricular ejection fraction in patients with heart failure.
AB  - BACKGROUND: Right ventricular (RV) global longitudinal strain (RV strain) is a
      sensitive measure of RV mechanics. Its relationship with standard clinical
      markers and long-term events in chronic systolic heart failure is not well
      established. The aim of this study was to examine the ability of RV strain to
      provide incremental prognostic value to left ventricular (LV) ejection fraction
      (LVEF) in patients with chronic systolic heart failure. METHODS: In 171 patients
      with chronic systolic heart failure (LVEF <= 35%), a retrospective substudy of RV
      strain was performed using Velocity Vector Imaging to analyze previously
      recorded, comprehensive echocardiographic images. Death, cardiac transplantation,
      and heart failure hospitalization were tracked for 5 years. RESULTS: In this
      study cohort (mean age, 57 +/- 14 years; mean LVEF, 25 +/- 6%), mean RV strain
      was -11.6 +/- 5.4%. More impaired RV strain was associated with increasing New
      York Heart Association class (rank-sums P < .0001) and greater LV volume (LV end
      systolic volume index: r = 0.35, P < .0001). Worse RV strain was associated with
      reduced LVEF (r = -0.45, P < .0001), worse LV diastolic dysfunction (E/e' septal:
      r = 0.19, P = .017; left atrial volume index: r = 0.18, P = .031), and standard
      indices of RV systolic and diastolic dysfunction (RV s': r = -0.43, P < .0001; RV
      e'/a': r = 0.16, P = .0040; right atrial volume index: r = 0.20, P = .015). RV
      strain predicted long-term adverse events (hazard ratio, 1.30; 95% confidence
      interval, 1.02-1.70; P = .037). Furthermore, RV strain >= -14.8% predicted
      adverse events after adjustment for age, LVEF, RV s', E/e' septal, and right
      atrial volume index. CONCLUSION: In patients with chronic systolic heart failure,
      worse RV strain provides prognostic value incremental to LV function.

PMID- 24679741
TI  - Prognostic meaning of coronary microvascular disease in type 2 diabetes mellitus:
      a transthoracic Doppler echocardiographic study.
AB  - BACKGROUND: The prognostic value of Doppler-derived coronary flow velocity
      reserve (CFVR) of the left anterior descending coronary artery in patients with
      type 2 diabetes with preserved left ventricular systolic function and without
      flow-limiting stenoses on angiography remains undetermined. METHODS: The study
      sample consisted of 144 patients with type 2 diabetes (82 men; mean age 62 +/- 10
      years) with chest pain or angina-equivalent symptoms, no histories of coronary
      artery disease, and echocardiographic ejection fractions >= 50%. All patients
      underwent dipyridamole stress echocardiography with CFVR assessment of the left
      anterior descending coronary artery by transthoracic Doppler echocardiography and
      coronary angiography showing normal coronary arteries or nonobstructive coronary
      artery disease. RESULTS: Mean CFVR was 2.44 +/- 0.57. On individual patient
      analysis, 109 patients (76%) had CFVR > 2, and 35 (24%) had CFVR <= 2. During a
      median follow-up period of 29 months (interquartile range, 14-44 months), 17 hard
      events (five deaths, 12 nonfatal myocardial infarctions) occurred. The annual
      hard-event rate was 13.9% in subjects with CFVR <= 2 and 2.0% in those with CFVR
      > 2. The annual event rate associated with CFVR <= 2 was significantly higher
      both in patients with left ventricular hypertrophy (P < .0001) and in those
      without left ventricular hypertrophy (P = .048). On Cox analysis, CFVR <= 2
      (hazard ratio, 11.20; 95% confidence interval, 3.07-40.92), and male sex (hazard
      ratio, 7.80; 95% confidence interval, 1.74-34.97) were independent prognostic
      indicators, whereas nonobstructive coronary artery disease was not an independent
      predictor of outcomes. CONCLUSIONS: Microvascular dysfunction before the
      occurrence of coronary artery involvement is a strong and independent predictor
      of outcomes in patients with type 2 diabetes. Vasodilator stress CFVR is a
      suitable tool to assess microvascular dysfunction in routine clinical practice.

PMID- 24679742
TI  - Incremental value of three-dimensional echocardiography in the evaluation of left
      ventricular size in mitral regurgitation: a follow-up study after mitral valve
      surgery.
AB  - BACKGROUND: Increased left ventricular (LV) dimensions are an indication for
      surgery in patients with asymptomatic mitral regurgitation, but M-mode or two
      dimensional measurements have known limitations. The aim of this study was to
      determine the value of three-dimensional echocardiography in predicting
      postoperative outcomes after mitral surgery. METHODS: Sixty-seven patients with
      severe asymptomatic or minimally symptomatic mitral regurgitation (69% men; mean
      age, 62 +/- 13 years) who underwent mitral valve surgery from January 2010 to
      December 2011 were studied. In addition to standard echocardiography, baseline
      three-dimensional echocardiography was performed for accurate quantification of
      LV size. Patients were followed over a median time of 1 month (interquartile
      range, 0-8 months) for postoperative development of atrial fibrillation or LV
      dysfunction. A multivariate regression analysis was performed to identify
      associations with events. RESULTS: Postoperative LV dysfunction developed in 15
      patients (22%), and 21 patients (31%) had postoperative atrial fibrillation.
      There was no association between two-dimensional end-systolic volume index and
      outcomes (hazard ratio, 1.02; P = .18). Postoperative atrial fibrillation or LV
      dysfunction was associated with baseline three-dimensional LV end-systolic volume
      index (hazard ratio, 1.06; 95% confidence interval, 1.04-1.16), independent of
      age and presence of coronary artery disease. LVESVi >= 40 mL/m(2) was the best
      cutoff value to predict postoperative events (sensitivity, 80%; specificity,
      85%). After adding LVESVi to a model containing clinical and echocardiographic
      parameters, net reclassification improvement was 0.27 (95% confidence interval,
      0.25-0.29; P = .024). CONCLUSIONS: LVESVi from three-dimensional echocardiography
      is an independent predictor of postoperative outcomes in patients with severe
      mitral regurgitation that is incremental to other clinical and echocardiographic
      variables.

PMID- 24679743
TI  - Identifying the limitations for growth in low performing piglets from birth until
      10 weeks of age.
AB  - The evolution of hyper-prolific pig breeds has led to a higher within-litter
      variation in birth weight and in BW gain during the nursery phase. Based on an
      algorithm developed in previous research, two populations from a pool of 368
      clinically healthy piglets at 6 weeks of age were selected: a low (LP) and a high
      (HP) performing population and their development was monitored until the end of
      the nursery phase (10 weeks of age). To understand the cause of the variation in
      growth between these populations we characterized the LP and HP piglets in terms
      of body morphology, behaviour, voluntary feed intake, BW gain, and apparent total
      tract and ileal nutrient digestibility. Piglets were housed individually and were
      fed a highly digestible diet. At selection, 6 weeks of age, the BW of LP and HP
      piglets were 6.8+/-0.1 and 12.2+/-0.1 kg, respectively. Compared with the LP
      piglets the HP piglets grew faster (203 g/day), ate more (275 g/day) from 6 to 10
      weeks of age and were heavier at 10 weeks (30.0 v. 18.8 kg, all P<0.01). Yet, the
      differences in average daily gain and average daily feed intake disappeared when
      compared per kg BW0.75. Assuming similar maintenance requirements per kg BW0.75
      the efficiency of feed utilization above maintenance was 0.1 g/g lower for the LP
      piglets (P=0.09).The gain : feed ratio was similar for both groups. LP piglets
      tended to take more time to touch a novel object (P=0.10), and spent more time
      eating (P<0.05). At 10 weeks, LP piglets had a higher body length and head
      circumference relative to BW (P<0.01). Relative to BW, LP had a 21% higher small
      intestine weight; 36% longer length, and relative to average FI, the small
      intestinal weight was 4 g/kg higher (both P=<0.01). Apparent total tract and
      ileal dry matter, N and gross energy digestibility were similar between groups
      (P>0.10). We concluded that the low performance of the LP piglets was due to
      their inability to engage compensatory gain or compensatory feed intake as
      efficiency of nutrient utilization and feed intake per kg BW0.75 was unaffected.
      LP piglets tend to be more fearful towards novel objects. The morphological
      comparisons, increased body length and head circumference relative to BW imply
      that LP piglets have an increased priority for skeletal growth. 

PMID- 24679744
TI  - Effect of SPME extraction conditions and humidity on the release of volatile
      lipid oxidation products from spray-dried emulsions.
AB  - The aim of the study was to investigate the effects of headspace solid-phase
      microextraction (HS-SPME) conditions and relative humidity (RH) on the release of
      volatile lipid oxidation products from spray-dried emulsions. Two model spray
      dried sunflower oil emulsions with a Na-caseinate-maltodextrin matrix were
      oxidised, stabilised at five RHs and analysed by HS-SPME-GC-MS for volatiles.
      Increased extraction temperature raised not only the overall release of volatile
      compounds but also altered the volatile profile. The obtained volatile profiles
      were dependent on the RH. This was mainly due to the humidity response of the
      matrix affecting e.g. its binding ability and hydrophilicity. Cross-linking of
      the emulsifying protein had a minor influence on the release. Both matrix-related
      factors and extraction conditions should thus be taken into account in
      interpretation of the HS-SPME results. On the other hand, being sensitive to
      changes in matrix composition and structure, the HS-SPME allows studying of
      matrix-related changes in foods. 

PMID- 24679745
TI  - Carbon isotope ratio (13C/12C) of pine honey and detection of HFCS adulteration.
AB  - Carbon isotope ratio ((13)C/(12)C=delta(13)C) of 100 pine honey samples collected
      from 9 different localities by Mugla region (Turkey) in years 2006, 2007 and 2008
      were investigated. The delta(13)Cprotein value of honey samples ranged between 
      23.7 and -26.60/00, while the delta(13)Choney value varied between -22.7 and 
      270/00. For 90% of the samples, the difference in the C isotope ratio of protein
      and honey fraction (delta(13)Cpro-delta(13)Chon) was -1.00/00 and/or higher.
      Therefore, it can be said that the generally anticipated minimum value of C
      isotope difference (-1.00/00) for honey is also valid for pine honey. On the
      other hand, C4 sugar value (%), which was calculated from the delta(13)Cpro
      delta(13)Chon difference, was found to be linearly correlated with the amount of
      adulterant (HFCS) in pine honey. These results indicate that C4 sugar value is a
      powerful criteria for detecting HFCS adulteration in pine honey. The
      delta(13)Choney and delta(13)Cprotein-delta(13)Choney values of the samples did
      not show any significant differences in terms of both year and locality (P>0.05),
      while the delta(13)Cprotein values showed significant differences due to year
      (P<0.05) but not due to locality (P>0.05).

PMID- 24679746
TI  - Influence of in vitro gastrointestinal digestion of fruit juices enriched with
      pine bark extract on intestinal microflora.
AB  - The selective antimicrobial effect of fruit juices enriched with pine bark
      extract (PBE) (0.5 g/L) has been studied before and after in vitro
      gastrointestinal digestion. PBE (a concentrate of water-soluble bioflavonoids,
      mainly including phenolic compounds) has been proven to have high stability to
      the digestion process. Pure phenolic compounds such as gallic acid had a high
      antimicrobial effect on Staphylococcus aureus and Escherichia coli, maintaining
      the lactic acid bacteria population (~100%). Otherwise, E. coli O157:H7 only
      growth 50% when PBE was added to the culture media, while a slight increase on
      the growth of lactobacilli and bifidobacteria was observed after exposition to
      the bark extract. Fresh fruit juices enriched with PBE showed the highest
      inhibitory effect on pathogenic intestinal bacterial growth, mainly E. coli and
      Enterococcus faecalis. The in vitro digestion process reduced the antibacterial
      effect of juices against most pathogenic bacteria in approximately 10%. However,
      the beneficial effect of fruit juices enriched with PBE (0.5 g/L) on gut
      microbiota is still considerable after digestion.

PMID- 24679747
TI  - Enzyme release of phenolics from muscadine grape (Vitis rotundifolia Michx.)
      skins and seeds.
AB  - Enzyme degradation of plant cell wall polysaccharides can potentially enhance the
      release of bioactive phenolics. The aim of this study was to evaluate various
      combinations of solvent and enzyme, enzyme type (cellulase, pectinase, beta
      glucosidase), and hydrolysis time (1, 4, 8, 24 h) on the release of muscadine
      grape skin and seed phenolics, and their antioxidant activities. Results showed
      that pre-treated muscadine skins and seeds with enzymes decreased total phenolic
      yield compared with solvent (50% ethanol) alone. Enzyme release of phenolics from
      skins of different muscadine varieties was significantly different while release
      from seeds was similar. Enzyme hydrolysis was found to shorten extraction time.
      Most importantly, enzyme hydrolysis modified the galloylated form of polyphenols
      to low molecular weight phenolics, releasing phenolic acids (especially gallic
      acid), and enhancing antioxidant activity.

PMID- 24679748
TI  - Antioxidant property of edible mushrooms collected from Ethiopia.
AB  - Two cultivated (P. ostreatus and L. edodes) and five wild (L. sulphureus, A.
      campestris, T. clypeatus, T. microcarpus and T. letestui) edible mushrooms were
      analyzed for their antioxidant activities, total phenolics, total flavonoids,
      phenolic profile and ergothioneine content. Results showed that A. campestris had
      the greatest antioxidant activity in all assays with lower EC50 (mg/ml) values of
      1.4, 3.6 and 0.035 for scavenging, reducing and chelating activities,
      respectively. To correlate well with activities, A. campestris also exhibited
      greater total phenolics and total flavonoids content of 14.6 mg GAE/g and 1.97 mg
      CE/g, respectively. The maximum concentration (MUg/g) of the individual phenolic
      compounds were 7.80 (P. ostreatus) for caffeic acid, 4.55 (T. letestui) for
      chlorogenic acid, 15.8 (T. microcarpus) for p-coumaric acid, 20.3 (A. campestris)
      for ferulic acid, 561.9 (A. campestris) for gallic acid, 38.7 (A. campestris) for
      p-hydroxybenzoic acid and 7.08 (A. campestris) for myricetin. All samples tested
      contained different amounts of ergothioneine ranging from 0.08 (L. sulphureus) to
      3.78 (P. ostreatus) mg/g in dry weight.

PMID- 24679750
TI  - Study on flavonoid migration from active low-density polyethylene film into
      aqueous food simulants.
AB  - The migration of flavonoids from low-density polyethylene (LDPE) film (0.4%, w/w)
      to aqueous food simulants over 16 weeks at 0, 15, and 30  degrees C was
      investigated. The migration amount of total flavonoids was calculated based on
      the rutin contents determined by high-performance liquid chromatography (HPLC).
      Diffusion and partition coefficients, along with the activation energy (Ea) were
      calculated based on Fick's second law. The results showed that the migration of
      flavonoids was influenced by temperature, time and the simulants. The Ea values
      for flavonoid diffusion were 49.2, 55.9, and 25.8 kJ mol(-1) in distilled water,
      4% acetic acid and 30% ethanol, respectively. This study indicated that the
      flavonoids in LDPE film easily migrated into food simulants; and this behaviour
      was related to the low Ea values of flavonoid diffusion, especially in ethanol at
      0-30  degrees C, when the antioxidants were released from the film.

PMID- 24679749
TI  - Biological activities of selected polyphenol-rich fruits related to immunity and
      gastrointestinal health.
AB  - Small fruits are a rich source of bioactive substances, including polyphenols,
      and are therefore suitable raw materials for the production of functional foods.
      In the current work, we studied the antioxidative properties of six fruits:
      rosehip, chokeberry, hawthorn, blackcurrant, blueberry and rowanberry via
      different methods (ORAC, TRAP, HORAC and inhibition of lipid peroxidation). Their
      effect on the production of reactive oxygen species (ROS) by phagocytes,
      antimicrobial properties against 11 human pathogens, and mitogenic effect on
      hamster spleen lymphocytes were also tested. Rosehip extract showed the highest
      antioxidant activity via ORAC, TRAP and HORAC assays, whereas blueberry extract
      was the most potent inhibitor of lipid peroxidation. All extracts inhibited ROS
      production of opsonized zymosan-activated phagocytes, indicating that extracts
      interfere with the signaling cascade of phagocyte activation upstream to the
      protein kinase C activation. Chokeberry, blackcurrant and rowanberry extracts
      revealed strong antimicrobial properties against a broad spectrum of
      microorganisms and also had the highest mitogenic activity. 

PMID- 24679751
TI  - Full substitution of fish oil with camelina (Camelina sativa) oil, with partial
      substitution of fish meal with camelina meal, in diets for farmed Atlantic salmon
      (Salmo salar) and its effect on tissue lipids and sensory quality.
AB  - Camelina oil (CO) and meal (CM) are potential replacements of fish meal (FM) and
      oil (FO) in aquaculture feeds. CO is high in alpha-linolenic acid (18:3omega3,
      ALA) (30%), with an omega3/omega6 ratio >1. This study tested diets with 100% CO,
      solvent extracted FM (SEFM) and partially substituted FM with 10% CM, in a 16
      week feeding trial with Atlantic salmon (initial weight 240 g fish(-1)). Final
      weight (529-691 g fish(-1)) was not affected by using 100% CO; however it was
      lower in groups fed SEFM and 10% CM diets. Total lipid in salmon flesh fed a diet
      with CO, SEFM and CM (22% ww(-1)) was significantly higher than FO flesh (14% ww(
      1)). There was no difference in the sensory quality of salmon fillets that were
      fed either FO or 100% CO diets. This was the first study to use CO as a complete
      FO replacement in diets for farmed Atlantic salmon.

PMID- 24679752
TI  - Identification of native angiotensin-I converting enzyme inhibitory peptides in
      commercial soybean based infant formulas using HPLC-Q-ToF-MS.
AB  - This work evaluates, the presence of native antihypertensive peptides in five
      soybean-based infant formulas (SBIFs). SBIFs peptide extracts (<10 kDa) and their
      sub-fractions (5-10 kDa, 3-5 kDa, and <3 kDa) from a variety of samples were
      obtained by ultrafiltration and ACE inhibitory activity was determined. The
      highest activities were observed in the smaller (<5 kDa) peptide fractions. A set
      of peptides present in various SBIFs were studied, and identified using HPLC-Q
      ToF-MS. Despite ACE inhibitory activity decreasing after in vitro
      gastrointestinal digestion, it still remained at a high value (IC50 values of
      18.2+/-0.1 and 4.9+/-0.1 MUg/mL). Peptides resisting the action of
      gastrointestinal enzymes were identified and compared to previously identified
      peptides, highlighting the presence of peptide RPSYT. This peptide was
      synthesised, its antihypertensive and antioxidant activity were evaluated, and
      its resistance to in vitro gastrointestinal digestion and to high processing
      temperatures were studied.

PMID- 24679753
TI  - Determination and chemometric evaluation of total aflatoxin, aflatoxin B1,
      ochratoxin A and heavy metals content in corn flours from Turkey.
AB  - Concentrations of the total aflatoxin, aflatoxin B1, aflatoxin B2, aflatoxin G1,
      aflatoxin G2, ochratoxin A, lead, cadmium, mercury, arsenic, copper, zinc and
      chromium in corn flour samples were determined. Eighteen corn flour samples that
      were obtained from different cities and villages in Turkey and 3 corn flour
      samples obtained from the UK. Determination of the different toxins was carried
      out using HPLC instrumentation after pre-separation using immunoaffinity columns
      that work through a mechanism of solid-phase extraction. An ICP-MS instrument was
      used for the heavy metal determinations. The results obtained from HPLC and ICP
      MS analyses of the corn flour samples showed that these samples contain
      detectable levels of most of the analytes but the mercury was at undetectable
      levels. A very strong statistical relationship was observed between Cr and total
      Aflatoxin and Aflatoxin B1; whereas Ochratoxin A was related to Cu and Zn
      concentrations using correlation analyses and principal component analyses. 

PMID- 24679754
TI  - Release properties of gel-type W/O/W encapsulation system prepared using
      enzymatically-modified starch.
AB  - A gel-based encapsulation system was developed by incorporating W/O/W emulsions
      and 4-alpha-glucanotransferase (4alphaGTase) treated starch capable of
      thermoreversible gel formation, and its physical and release characteristics were
      investigated as functions of preparation conditions and temperature. Release
      properties of the W/O/W gels were affected by stability and encapsulation
      efficiency (EE) of W/O/W emulsions embedded within. Lower EE caused by longer
      sonication time increased fast release dye portion, which resulted in higher dye
      release rate, even though emulsion stability improved at longer sonication time.
      Lower dye release rate of W/O/W gels prepared with relatively higher W/O volume
      fractions slightly increased as temperature increased from room temperature to 90
      degrees C. However, samples prepared with relatively lower W/O volume fractions
      showed higher dye release rate and a larger increase at 90  degrees C. The
      4alphaGTase-treated starch gel improved W/O/W emulsion stability and thus
      retarded dye release even at 90  degrees C.

PMID- 24679755
TI  - Metabolomic approaches for orange origin discrimination by ultra-high performance
      liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.
AB  - In this work, hybrid quadrupole time-of-flight mass spectrometer (QTOF MS)
      coupled to ultra high performance liquid chromatography (UHPLC) has been used for
      biomarkers identification for correct authentication of Valencia (Spain) oranges.
      Differentiation from foreign Argentinean, Brazilian and South African oranges has
      been carried out using XCMS application and multivariate analysis to UHPLC-(Q)TOF
      MS data acquired in both, positive and negative ionisation modes. Several markers
      have been found and corroborated by analysing two seasons samples. A seasonal
      independent marker was found and its structure elucidated using accurate mass
      data and MS(E) fragmentation spectrum information. Empirical formula was searched
      in Reaxys database applying sub-structure filtering from the fragments obtained.
      Three possible structures were found and citrusin D, a compound present in sweet
      oranges, has been identified as the most plausible as it fits better with the
      product ion scan performed for this compound. As a result of data obtained in
      this work, citrusin D is suggested as a potential marker to distinguish the
      geographic origin of oranges. 

PMID- 24679756
TI  - Application of 1H NMR for the characterisation of cocoa beans of different
      geographical origins and fermentation levels.
AB  - This study reports for the first time the use of (1)H NMR technique combined with
      chemometrics to study the metabolic profile of cocoa (Theobroma cacao L.) beans
      of different varieties, origin and fermentation levels. Results of PCA applied to
      cocoa bean (1)H NMR dataset showed that the main factor influencing the cocoa
      bean metabolic profile is the fermentation level. In fact well fermented brown
      beans form a group clearly separated from unfermented, slaty, and underfermented,
      violet, beans, independently of the variety or geographical origin. Considering
      only well fermented beans, the metabolic profile obtained by (1)H NMR permitted
      to discriminate between some classes of samples. The National cocoa of Ecuador,
      known as Arriba, showed the most peculiar characteristics, while the samples
      coming from the African region showed some similar traits. The dataset obtained,
      representative of all the classes of soluble compounds of cocoa, was therefore
      useful to characterise fermented cocoa beans as a function of their origin and
      fermentation level. 

PMID- 24679757
TI  - Production and characterization of crude and refined oils obtained from the co
      products of Nile tilapia and hybrid sorubim processing.
AB  - In this study, crude oil was extracted by heating and filtering of the residual
      fat obtained from the processing of mechanically separated meats of Nile tilapia
      (Oreochromis niloticus) and hybrid sorubim (Pseudoplatystoma corruscans*P.
      fasciatum) for protein concentrate obtaining. The crude oil was refined by the
      following steps: degumming with 85% phosphoric acid, neutralization with 20%
      NaOH, washing with hot water at 85  degrees C, drying at 90  degrees C,
      clarification with activated charcoal and filtration with diatomaceous earth and
      anhydrous sodium sulfate. The quality of crude and refined oils was verified by
      acidity, peroxide, iodine, refractive, and saponification indexes, beyond
      moisture, lipid and free fatty acids contents, and density. The results show that
      the refining reduced the acidity index of the crude oil, however, favored the oil
      oxidation, as demonstrated by the increase in peroxide index. In most of the
      cases there was no change in the identity of the fish oils.

PMID- 24679758
TI  - Isothiocyanates may chemically detoxify mutagenic amines formed in heat processed
      meat.
AB  - Meat consumption represents a dietary risk factor increasing the incidence of
      common cancers, probably due to carcinogenic amines (HAAs) formed upon meat
      heating. Interestingly, cancers whose incidence is increased by meat consumption,
      are decreased in populations consuming brassica vegetables regularly. This
      inverse correlation is attributed to brassica anticarcinogenic components,
      especially isothiocyanates (ITCs) that stimulate detoxification of food
      carcinogens. However, ITC reactivity towards amines generating stable thioureas,
      may also decrease mutagenicity of processed meat. We confirmed here that
      combining meat with cabbage (fresh or lyophilized), in proportions found in
      culinary recipes, limited by 17-20% formation of HAAs and significantly lowered
      mutagenic activity of fried burgers. Moreover, MeIQx mutagenicity was lowered in
      the presence of ITCs, as well as for synthetic ITC-MeIQx conjugates. This
      suggests that formation of thioureas could lead to chemical detoxification of
      food carcinogens, reducing the cancer risk associated with meat consumption. 

PMID- 24679759
TI  - Natural co-occurrence of mycotoxins in wheat grains from Italy and Syria.
AB  - This article describes the application of an analytical method for the detection
      of 25 mycotoxins in wheat grain based on simultaneous extraction using matrix
      solid-phase dispersion (MSPD) followed by liquid chromatography coupled to tandem
      mass spectrometry, a hybrid triple quadrupole-linear ion trap mass spectrometer
      (QTrap(r)). Information Dependent Acquisition (IDA), an extra confirmation tool
      for samples that contain the target mycotoxins, was used. The analysis of 40
      Syrian and 46 Italian wheat grain samples interestingly showed that Syrian
      samples were mainly contaminated with ochratoxin A and aflatoxins, whereas
      Italian samples with deoxynivalenol and 15-acetyldeoxynivalenol. Emerging
      Fusarium mycotoxins were predominant in Italian samples compared to the Syrian.
      Among the analysed samples, only one was found containing zeralenone with level
      above the maximum European recommended concentration (100 ppb). These results
      confirm that climatic differences between Syria and Italy, both in Mediterranean
      basin, play a key role in the diversity of fungal genera and mycotoxins in wheat
      grains.

PMID- 24679760
TI  - Extraction of carbamate pesticides in fruit samples by graphene reinforced hollow
      fibre liquid microextraction followed by high performance liquid chromatographic
      detection.
AB  - Graphene reinforced hollow fibre liquid phase microextraction combined with high
      performance liquid chromatography-diode array detection was developed for the
      determination of some carbamate pesticides (metolcarb, carbaryl, isoprocarb, and
      diethofencarb) in fruit samples. The main parameters that affect the extraction
      efficiency for the carbamates were investigated. Under the optimum conditions, a
      good linearity was observed in the range of 1.0-100.0 ng g(-1) for carbaryl and
      3.0-100.0 ng g(-1) for the other three analytes, with the correlation
      coefficients (r) of 0.9965-0.9993. The limits of detection of the method ranged
      from 0.2 to 1.0 ng g(-1). The relative standard deviations were in the range from
      6.2% to 7.8%. The results indicated that the developed method is sensitive and
      efficient for the determination of the carbamate pesticides in fruit samples.

PMID- 24679761
TI  - Effect of pulse electric fields (PEF) on accumulation of magnesium and zinc ions
      in Saccharomyces cerevisiae cells.
AB  - Cultures of Saccharomyces cerevisiae were treated with PEF to improve
      simultaneous accumulation of magnesium and zinc ions in the biomass. The results
      showed that the ions concentration in the medium and their mutual interactions
      affect accumulation in cells. Increasing the concentration of one ion in the
      medium reduced the accumulation of the second one, in the control as well as in
      the cells treated with PEF. Under optimized conditions, that is, on 15 min
      exposure of the 20 h grown culture to PEF of 5.0 kV/cm and 20 MUs pulse width,
      accumulation of magnesium and zinc in yeast biomass reached maximum levels of
      2.85 and 11.41 mg/gd.m., respectively, To summarize, optimization of ion pair
      concentration and PEF parameters caused a 1.5 or 2-fold increase of magnesium and
      zinc accumulation, respectively, in S. cerevisiae.

PMID- 24679762
TI  - Immobilized phospholipase A1-catalyzed modification of phosphatidylcholine with n
      3 polyunsaturated fatty acid.
AB  - n-3 Polyunsaturated fatty acids (n-3 PUFA)-enriched phosphatidylcholine (PC) was
      successfully produced with fatty acid from fish oil and PC from soybean by
      immobilized phospholipase A1-catalyzed acidolysis. Detailed studies of
      immobilization were carried out, and Lewatit VP OC 1600 was selected as a carrier
      for preparation of immobilized phospholipase A1, which was used for modification
      of PC by acidolysis. For acidolysis of PC with n-3 PUFA, the effects of several
      parameters, namely, water content, temperature, and enzyme loading on the
      reaction time course were investigated to determine optimum conditions. The
      optimum water content, temperature, and enzyme loading were 1.0%, 55  degrees C,
      and 20%, respectively. The highest incorporation (57.4 mol%) of n-3 PUFA into PC
      was obtained at 24h and the yield of PC was 16.7 mol%. The yield of PC increased
      significantly by application of vacuum, even though a slight decrease of n-3 PUFA
      incorporation was observed.

PMID- 24679763
TI  - Allergenic properties and differential response of walnut subjected to processing
      treatments.
AB  - The aim of this study was to investigate changes in walnut allergenicity after
      processing treatments by in vitro techniques and physiologically relevant assays.
      The allergenicity of walnuts subjected to high hydrostatic pressure and
      thermal/pressure treatments was evaluated by IgE-immunoblot and antibodies
      against walnut major allergen Jug r 4. The ability of processed walnut to cross
      link IgE on effector cells was evaluated using a rat basophil leukaemia cell line
      and by skin prick testing. Susceptibility to gastric and duodenal digestion was
      also evaluated. The results showed that walnuts subjected to pressure treatment
      at 256 kPa, 138  degrees C, were able to diminish the IgE cross-linking capacity
      on effector cells more efficiently than high pressure treated walnuts. IgE
      immunoblot confirmed these results. Moreover, higher susceptibility to digestion
      of pressure treated walnut proteins was observed. The use of processed walnuts
      with decreased IgE binding capacity could be a potential strategy for walnut
      tolerance induction.

PMID- 24679764
TI  - Relation of sensory perception with chemical composition of bioprocessed
      lingonberry.
AB  - The impact of bioprocessing on lingonberry flavour was studied by sensory
      evaluation and chemical analysis (organic acids, mannitol, phenolic compounds,
      sugars and volatile compounds). Bioprocessing of lingonberries with enzymes,
      lactic acid bacteria (LAB) or yeast, or their combination (excluding pure LAB
      fermentation) affected their perceived flavour and chemical composition.
      Sweetness was associated especially with enzyme treatment but also with
      enzyme+LAB treatment. Yeast fermentation caused significant changes in volatile
      aroma compounds and perceived flavour, whereas minor changes were detected in LAB
      or enzyme-treated berries. Increased concentration of organic acids, ethanol and
      some phenolic acids correlated with perceived fermented odour/flavour in yeast
      fermentations, in which increase in benzoic acid level was significant. In
      enzymatic treatment decreasing anthocyanins correlated well with decreased
      perceived colour intensity. Enzyme treatment is a potential tool to decrease
      naturally acidic flavour of lingonberry. Fermentation, especially with yeast,
      could be an interesting new approach to increase the content of natural
      preservatives, such as antimicrobial benzoic acid. 

PMID- 24679765
TI  - Does a sorghum-cowpea composite porridge hold promise for contributing to
      alleviating oxidative stress?
AB  - The effect of compositing red non-tannin sorghum with cream-coloured cowpea and
      porridge preparation on phenolic profile and radical scavenging activity was
      studied. A maize-soybean composite porridge representing a similar product on the
      South African market was used as reference sample. UPLC-QToF-MS-ESI was used to
      determine phenolic composition of the grain flours, their composites and
      porridges. Total phenolic content was determined using Folin-Ciocalteu method
      while radical scavenging activity was determined using the ABTS, DPPH and NO
      radical scavenging assays. Four benzoic acid derivatives and five cinnamic acid
      derivatives were identified in the samples. The predominant flavonoid subclasses
      identified in sorghum were flavan-3-ols, flavanones and flavones while cowpea had
      mainly flavan-3-ols and flavonols with soybean having mainly isoflavones.
      Compositing the cereals with legumes significantly (p<0.01) increased their total
      flavonoid content and radical scavenging activities. Sorghum-cowpea composite
      porridge showed better promise in contributing to alleviating radical induced
      oxidative stress than maize-soybean composite porridge. 

PMID- 24679766
TI  - Impact of shortwave ultraviolet (UV-C) radiation on the antioxidant activity of
      thyme (Thymus vulgaris L.).
AB  - Thyme is a good source of antioxidant compounds but it can be contaminated by
      microorganisms. An experimental fluid bed ultraviolet (UV) reactor was designed
      for microbial decontamination of thyme samples and the effect of shortwave
      ultraviolet light (UV-C) radiation on antioxidant properties of thyme was
      studied. Samples were exposed to UV-C radiation for 16 or 64 min. UV-C treatment
      led to 1.04 and 1.38 log CFU/g reduction of total aerobic mesophilic bacteria
      (TAMB) counts. Hunter a(*) value was the most sensitive colour parameter during
      UV-C treatment. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging activity of
      extracts was not significantly affected by UV-C. Addition of thyme extracts at
      0.15 and 0.3 MUmol GAE/ml emulsion delayed the formation of lipid hydroperoxides
      and headspace hexanal in the 5.0%(wt) corn oil-in-water emulsion from 4 to 9 and
      14 days, respectively. No significant changes in oxidation rates were observed
      between UV-C treated and untreated samples at same concentrations.

PMID- 24679767
TI  - Influence of pearling process on phenolic and saponin content in quinoa
      (Chenopodium quinoa Willd).
AB  - The aim of this work was to obtain sweet quinoa seeds by a pearling process.
      Thus, two different pearling degrees (20% and 30%) were tested. Moreover, the
      effect of pearling process on saponins and phenolic content in quinoa were
      evaluated. To this end, GC-MS methodology was used to identify and quantify the
      saponins and reversed phase-high performance liquid chromatography coupled to DAD
      and mass spectrometer detectors was applied to study the phenolic composition. As
      expected, whole quinoa had the highest saponins and phenolics contents. An
      abrasion degree of 30% was necessary to obtain sweet quinoa (with a total saponin
      content lower than 110 mg/100 g). Obviously, this process caused a decrease of
      21.5% and 35.2% of free and bound phenolic compounds, respectively. However, this
      decrease was lower if compared with other cereals. Thus, pearling process is a
      promising sustainable method to obtain sweet quinoa with a "green" approach.

PMID- 24679768
TI  - Effect of antioxidant potential of tropical fruit juices on antioxidant enzyme
      profiles and lipid peroxidation in rats.
AB  - Fruits are a rich source of a variety of biologically active compounds that can
      have complementary and overlapping mechanisms of action, including
      detoxification, enzyme modulation and antioxidant effects. Although the effects
      of tropical fruits have been examined individually, the interactive antioxidant
      capacity of the bioactive compounds in these formulations has not been
      sufficiently explored. For this reason, this study investigated the effect of two
      tropical fruit juices (FA and FB) on lipid peroxidation and antioxidant enzymes
      in rats. Seven groups, with eight rats each, were fed a normal diet for 4 weeks,
      and were force-fed daily either water (control), 100, 200, or 400 mg of FA or FB
      per kg. The results showed that the liver superoxide dismutase and catalase
      activities (FA200), erythrocytes glutathione peroxidase (FB400) and
      thiobarbituric acid-reactive substances (FB100, FA400, FB200, FB400) were
      efficiently reduced by fruit juices when compared with control; whereas HDL-c
      increased (FB400).

PMID- 24679769
TI  - Impact of high-intensity ultrasound on the formation of lactulose and Maillard
      reaction glycoconjugates.
AB  - The impact of high-intensity ultrasound (US) on the formation of lactulose during
      lactose isomerization and on the obtention of lysine-glucose glycoconjugates
      during Maillard reaction (MR) has been studied, respectively, in basic and
      neutral media. As compared to equivalent conventional heat treatments, a higher
      formation of furosine, as indicator of initial steps of MR, was observed together
      with more advance of the reaction in US treated samples, this effect being more
      pronounced with the increase of US amplitude (50-70%) and temperature (25-40 
      degrees C). Regarding the influence of US on lactulose formation, in general, in
      a buffered system (pH 10.0), US at 70% of amplitude and 60  degrees C increased
      the rate of lactose isomerization, higher values of lactulose, epilactose and
      galactose being observed in comparison to conventional heating. The results of
      this work showed an acceleration of both reactions by US, indicating its
      usefulness to promote the formation of functional ingredients.

PMID- 24679770
TI  - Determination of synthetic food dyes in commercial soft drinks by TLC and ion
      pair HPLC.
AB  - Synthetic food colourings were analyzed on commercial carbonated orange and grape
      soft drinks produced in Ceara State, Brazil. Tartrazine (E102), Amaranth (E123),
      Sunset Yellow (E110) and Brilliant Blue (E133) were extracted from soft drinks
      using C18 SPE and identified by thin layer chromatography (TLC), this method was
      used to confirm the composition of food colouring in soft drinks stated on label.
      The concentration of food colouring in soft drink was determined by ion-pair high
      performance liquid chromatography with photodiode array detection. The results
      obtained with the samples confirm that the identification and quantification
      methods are recommended for quality control of the synthetic colours in soft
      drinks, as well as to determine whether the levels and lables complies with the
      recommendations of food dyes legislation. 

PMID- 24679771
TI  - Solid phase microextraction coupled to liquid chromatography. Analysis of
      organosulphur compounds avoiding artifacts formation.
AB  - This work proposes the novel application of a microextraction technique, solid
      phase microextraction (SPME), coupled to liquid chromatography with UV detection
      (HPLC-UV) for the analysis of organosulfur compounds (OSCs) in garlic samples.
      Additionally, a comparative study of OSCs profiles obtained by SPME coupled to
      HPLC-UV and gas chromatography with flame photometric detector (GC-FPD),
      respectively; was carried out. This study provided complementary evidence about
      OSCs's lability and "artifacts" formation during the analytical process. Raw,
      cooked and distilled garlic samples were considered. The target analytes were
      diallyl disulphide (DADS), diallyl sulphide (DAS), diallyl trisulphide (DATS),
      allicin, 3-vinyl-4H-1,3-dithiin (3-VD), 2-vinyl-4H-1,2-dithiin (2-VD) and (E)-
      and (Z)-ajoene, which are the most important OSCs with biological activities
      present in raw and processed garlic. The coupling of SPME and HPLC showed to be
      reliable, fast, sensible and selective methodology for OSCs analysis.

PMID- 24679772
TI  - Mass spectrometry-based metabolomics approach to determine differential
      metabolites between regular and non-alcohol beers.
AB  - Non-alcohol beers show taste deficiencies in relation to regular (alcohol) beers
      as shown by consumer evaluation. In this study, multivariate statistical analysis
      of data obtained by ultra-performance liquid chromatography-mass spectrometry
      (UPLC-MS) measurements was applied to determining differential metabolites
      between two regular (R1 and R2) and their related low- and non-alcohol beers (F1
      and F2, respectively) from a Spanish manufacturer, as well as between F1 and F2
      and two non-alcohol beers (F3 and F4) from a non-Spanish producer. Principal
      component analysis (PCA) of data from UPLC-MS measurements with electrospray
      ionization in negative mode was able to separate the six beers. Sugar content was
      6-fold and 2-fold higher in F2 and F1 than in R2 and R1, respectively.
      Isoxanthohumol and hop acid contents decreased in F2 as compared with R2 but kept
      in F1 similar to R1. Results are discussed in relation to valued taste
      characteristics of each beer type. 

PMID- 24679773
TI  - Sulphur-containing compounds of durian activate the thermogenesis-inducing
      receptors TRPA1 and TRPV1.
AB  - Durian (Durio zibethinus Murr.) is classified as a body-warming food in Indian
      herbalism, and its hyperthermic effect is empirically known in Southeast Asia. To
      investigate the mechanism underlying this effect, we focused on the thermogenesis
      inducing receptors, TRPA1 and TRPV1. Durian contains sulphides similar to the
      TRPA1 and TRPV1 agonists of garlic. Accordingly, we hypothesized that the
      thermogenic effect of durian is driven by sulphide-induced TRP channel
      activation. To investigate our hypothesis, we measured the TRPA1 and TRPV1
      activity of the sulphur-containing components of durian and quantified their
      content in durian pulp. These sulphur-containing components had a stronger effect
      on TRPA1 than TRPV1. Furthermore, sulphide content in the durian pulp was
      sufficient to evoke TRP channel activation and the main agonist was diethyl
      disulphide. From these results, we consider that the body-warming effect of
      durian is elicited by TRPA1 activation with its sulphides, as can be seen in
      spices. 

PMID- 24679774
TI  - Immunochemical determination of fluoroquinolone antibiotics in cattle hair: a
      strategy to ensure food safety.
AB  - Enrofloxacin (ERFX) is a synthetic antibiotic of the fluoroquinolone (FQ) family,
      which is commonly administered in veterinary medicine. ERFX and its metabolite,
      ciprofloxacin (CPFX), have been reported to accumulate in hair of treated
      animals. Therefore, hair analysis is an attractive non-invasive alternative to
      control misuse of such antibiotic and to ensure food safety by preventing such
      food derived products arrive to the consumer. In this context, an immunochemical
      analytical protocol has been established to detect ERFX and CPFX residues in
      cattle hair samples. Unpigmented and pigmented hair were collected from ERFX
      treated and non-treated calves, and the aqueous NH4OH extracts were directly
      analyzed by ELISA, being possible to achieve limits of detection in the range of
      10-30 MUg kg(-1). A good concordance between HPLC and ELISA measurements was
      observed. The results demonstrate the potential of the immunochemical procedure
      reported here to rapidly screen and quantitate FQ residues in hair samples.

PMID- 24679775
TI  - Optimising aroma quality in curry sauce products using in vivo aroma release
      measurements.
AB  - Reducing fat content in foods to meet consumers' preferences and to address the
      obesity issue is a key task for food manufacturers but simply reducing fat
      content affects aroma quality adversely. Measuring the aroma release from regular
      and low-fat samples during eating to rebalance the aroma release has proved
      successful in model systems. Here, the reformulation of the spice content in a
      low fat curry sauce is described. Volatile markers of the key spices (coriander,
      cumin and turmeric) were selected and used to measure aroma release in regular
      (10 g oil/100 g) and low (2.5 or 5 g oil/100 g) fat sauces. Regression models
      were used to adjust the ingredient formulation so that the aroma release profiles
      in vivo were the same for the regular and reduced oil curry sauces and sensory
      analysis showed no significant difference between these samples. Despite the
      complexity of spice aromas, rebalancing was successful.

PMID- 24679776
TI  - Effect of phytosterols on textural and melting characteristics of cheese spread.
AB  - In the present study phytosterols (have hypocholesterolemic effect) have been
      used in processed cheese spread (PCS) to enhance its functionality and its effect
      on textural and melting properties have been evaluated at three different levels
      of addition (2%, 3% and 4%). On textural attributes, the firmness of the PCS at
      3% and 4% of phytosterols addition were significantly (p<0.05) higher as compared
      to the control. All the phytosterols incorporated cheese spread samples were
      significantly higher (p<0.05) in work of shear as compared to the control. As the
      levels of phytosterols addition were increased in cheese spread from 0 to 4%, a
      sharp, steady and significant (p<0.05) decrease in work of adhesion was noticed.
      The RVATM cheese melt viscosity index of all the phytosterols incorporated cheese
      spread samples were significantly (p<0.05) lower as compared to the control. 

PMID- 24679777
TI  - Microencapsulation of pulp and ultrafiltered cactus pear (Opuntia ficus-indica)
      extracts and betanin stability during storage.
AB  - Pulp (CP) and ultrafiltered (UF) cactus pear extracts were encapsulated with
      Capsul (C) by applying a central composite design (CP-C and UF-C systems) by
      spray-drying. To evaluate the effect of the extract, microparticles obtained
      under optimal conditions were characterised and stored at 60  degrees C.
      Betacyanin and betaxanthin encapsulation efficiency reached values above 98% for
      both systems studied. This efficiency was attributed to strong interactions
      between betalains and the polymer. Betalain degradation in CP-C and UF-C
      microparticles followed pseudo-first order kinetics. The betacyanin degradation
      rate constant was significantly higher for CP-C than for UF-C. These results
      suggested that the mucilage or higher sugar content of CP increased the
      hygroscopicity of the CP-C microparticles, leading to the degradation of
      betalain. The hydrolysis pathway was the main mechanism of betanin degradation
      during microparticle storage. These results demonstrate the potential utility of
      both CP-C and UF-C microparticles as natural colourants for healthy foods.

PMID- 24679778
TI  - The effect of sugars on the retention of ethyl butyrate by gellan gels.
AB  - The effect of sucrose, glucose and fructose on the retention of ethyl butyrate by
      low acyl gellan gels was investigated by static headspace gas chromatography. The
      air/biopolymer partition coefficient (K) and percentage of retention (R%) were
      determined. When 5 g of sample were left to equilibrate at 37  degrees C for 24
      h, the obtained results were explained in terms of gel rigidity, as increased
      rigidity resulted in increased aroma retention. Glucose showed the greatest aroma
      release among the sugars and resulted in either the same or increased aroma
      release with increasing concentration. Increasing concentrations of fructose and
      sucrose did not alter aroma release significantly. For 15 g of sample mass,
      sucrose exhibited the lowest partition coefficient values among the sugars. The
      two higher sucrose concentrations resulted in decreased coefficient values. For
      fructose and glucose, aroma retention decreased with increasing concentration.
      The percentage of retention values were positive for all sugars, throughout their
      concentration range and for both experiments.

PMID- 24679779
TI  - Assessment of aflatoxins, ochratoxin A and zearalenone in breakfast cereals.
AB  - Aflatoxins (AFs), ochratoxin A (OTA) and zearalenone (ZEN) were analysed in 237
      breakfast cereal samples collected from central areas of Punjab, Pakistan.
      According to the results, 41% of the samples were found contaminated with AFs,
      out of which 16% and 8% samples were found to be above the European Union (EU)
      maximum content for AFB1 and total AFs, respectively. About 48% samples were
      found contaminated with OTA and 30% samples were found to be above the EU maximum
      content. The results have shown that 53% samples of breakfast cereals were found
      contaminated with ZEN and 8% samples were found to be above the permissible limit
      of EU. The highest mean level of AFB1 and total AFs were found in semolina i.e.
      3.60 and 4.55 MUg/kg, respectively. Similarly, semolina was the highest
      contaminated breakfast cereal for OTA (3.90 MUg/kg), while cornflakes (brand B)
      was found highest contaminated with ZEN (13.45 MUg/kg).

PMID- 24679780
TI  - Protective effects of equimolar mixtures of monomer and dimer of dehydrozingerone
      with alpha-tocopherol and/or ascorbyl palmitate during bulk lipid autoxidation.
AB  - Protective effects of recently synthesised dehydrozingerone, M1OH (which is one
      half of the molecule of curcumin) and dimer of dehydrozingerone, D1(OH)2, as
      individual compounds (1 mM) and as equimolar binary (1:1) and ternary (1:1:1)
      mixtures with alpha-tocopherol (TOH) and/or ascorbyl palmitate (AscPH), were
      studied during bulk lipid autoxidation at 80  degrees C. The highest oxidation
      stability of lipid substrate, in the presence of individual compounds, was found
      for TOH, followed by D1(OH)2 and M1OH, determined from the main kinetic
      parameters (antioxidant efficiency, reactivity and capacity). AscPH did not show
      any protective effect. Synergism was obtained for the binary mixtures of
      (TOH+AscPH) [42.4%], (M1OH+TOH) [32.4%] and (M1OH+AscPH) [35.6%] and for the
      ternary mixture of (M1OH+TOH+AscPH) [28.7%]. Different protective effects
      observed were explained on the basis (of results) of TOH regeneration and its
      content determined by HPLC. These antioxidant binary and ternary mixtures can be
      used as functional components of foods with health-promoting effects.

PMID- 24679781
TI  - Role of carotenoid type on the effect of thermal processing on bioaccessibility.
AB  - Cell walls and chromoplast substructures constitute natural structural barriers
      governing carotenoid bioaccessibility. In order to enhance carotenoid
      bioaccessibility, thermal processes were applied to fractions surrounded by
      different levels of structural barriers. The matrices studied were orange
      carrots, red carrots, red tomatoes and atomic red carrots. In the case of
      carrots, no effect of thermal treatments on carotenoid bioaccessibility at the
      chromoplast level was obtained. However, in the case of tomatoes, lycopene
      bioaccessibility decreased upon thermal processing of chromoplasts. At the cell
      cluster level, low intensities of thermal processing resulted in a decrease of
      beta-carotene and lycopene bioaccessibility. Nonetheless, at high intensities of
      thermal processing, only beta-carotene bioaccessibility was increased. This
      observation was confirmed by the results obtained in the matrix rich in both
      types of carotenoids (atomic red carrots). It was therefore suggested, that the
      type of carotenoid constitutes an important factor determining the effect of
      thermal processing on their bioaccessibility. 

PMID- 24679782
TI  - Partial purification and characterization of polyphenol oxidase from persimmon.
AB  - Activity of polyphenol oxidase (PPO) from "Rojo Brillante" persimmon (Diospyros
      kaki L.) fruits was characterized. Crude extracts were used for characterization
      of enzyme activity and stability at different temperatures (60, 70 and 80 
      degrees C), pHs (from 3.5 to 7.5) and substrate concentrations (catechol from 0
      to 0.5M). Maximum enzyme activity was reached at pH 5.5 and 55  degrees C. Enzyme
      stability was higher than PPO activities found in other natural sources, since
      above pH 5.5 the minimum time needed to achieve an enzyme inactivation of 90% was
      70 min at 80  degrees C. However, at pH 4.0 the enzyme stability decreased,
      reaching inactivation levels above 90% after 10 min even at 60  degrees C. Thus
      it was concluded that acidification can circumvent browning problems caused by
      PPO activity. Moreover, polyacrylamide gel electrophoresis of the enriched
      extract revealed the presence of at least four bands with strong oxidase
      activity, suggesting the existence of different PPO isoforms.

PMID- 24679783
TI  - Tannin analysis of chestnut bark samples (Castanea sativa Mill.) by HPLC-DAD-MS.
AB  - In the present investigation, an HPLC-DAD/ESI-MS method for the complete analysis
      of tannins and other phenolic compounds of different commercial chestnut bark
      samples was developed. A total of seven compounds (vescalin, castalin, gallic
      acid, vescalagin, 1-O-galloyl castalagin, castalagin and ellagic acid) were
      separated and quantified, being 1-O-galloyl castalagin tentatively identified and
      found for the first time in chestnut bark samples. Thus, this method provided
      information regarding the composition and quality of chestnut bark samples, which
      is required since these samples are commercialised due to their biochemical
      properties as ingredients of food supplements. 

PMID- 24679784
TI  - Thermomechanical effects of co-solute on the structure formation of bovine serum
      albumin.
AB  - The effect of glucose syrup on the structural properties of bovine serum albumin
      has been addressed in preparations from low to high solids. Fifteen percent
      protein was mixed with the co-solute at concentrations up to 65% and subjected to
      thermal treatment to examine the changes in phase and state transitions.
      Thermomechanics were the working protocol being carried out with micro
      differential scanning calorimetry and small deformation dynamic oscillation.
      Results argue that protein molecules have been extensively stabilised by the
      addition of a co-solute, recorded via a delayed thermal denaturation. Further,
      increasing the glucose syrup enhanced polymer-polymer interactions leading to
      stronger networks following thermal denaturation of the globular protein.
      Condensed BSA/glucose syrup mixtures, i.e. at 80% solids, were cooled at subzero
      temperatures to exhibit a considerable state of vitrification. Molecular
      relaxation phenomena were successfully followed using theoretical concepts from
      synthetic polymer research to yield the mechanical glass transition temperature. 

PMID- 24679785
TI  - The interaction of phenolic acids with Fe(III) in the presence of citrate as
      studied by isothermal titration calorimetry.
AB  - Under physiological conditions, exogenous chelators such as polyphenols might
      interact with non-protein bound ferric complexes, such as Fe(III)-citrate.
      Additionally, Fe(III) and citrate are widely distributed in various fruits and
      vegetables which are also rich in phenolic acids. In this study, we focus on the
      interaction between phenolic acids (gallic acid, methyl gallate and
      protocatechuic acid) and Fe(III) in the presence of excessive citrate by
      isothermal titration calorimetry (ITC) for thermodynamic studies, and stopped
      flow absorption spectrometry for fast kinetic studies. Results reveal that all of
      these three phenolic acids can bind to the Fe(III) with the same stoichiometry
      (3:1). Moreover, the binding constants of these three compounds with Fe(III) are
      greatly dependent on ligand structure, and are much higher than that of Fe(III)
      citrate. Based on their stoichiometry and superhigh binding constants, it is most
      likely that these three phenolic acids can displace the citrate to bind with one
      iron(III) ion to form a stable octahedral geometric structure, albeit at
      different rates. These findings shed light on the interaction between phenolic
      acids and Fe(III) in the presence of citrate under either physiological
      conditions or in a food system. 

PMID- 24679786
TI  - Risks of dietary acrylamide exposure: a systematic review.
AB  - Acrylamide (AA) is a probable human carcinogen found in carbohydrate-rich foods
      that have been heated to high temperatures. AA dietary exposure has been
      associated to development of health problems. We perform a systematic review to
      elucidate the association of dietary AA exposure and human health problems.
      Articles were screened by reading titles and abstracts before the full text of
      eligible articles was read (kappa=0.824). Data were harvested by two reviewers
      and checked by a third. Forty-one articles were analyzed and assessment of
      dietary exposure proved to be far from uniform and suffered from limitations that
      possibly impact on the validity of outcomes with relation to human health. Risk
      assessment of dietary acrylamide exposure is in need of high quality methods for
      evaluating dietary exposure and validated acrylamide content databases. 

PMID- 24679787
TI  - Antioxidant/antiradical properties of microwave-assisted extracts of three wild
      edible mushrooms.
AB  - A microwave-assisted extraction (MAE) process for polyphenols from three wild
      edible mushrooms was studied. The optimal extraction conditions were found to be
      methanol concentration of 80%, extraction temperature of 80  degrees C, and
      extraction time of 5 min. Different antioxidant assays (i.e., total antioxidant
      capacity (TAC) and total phenolic content (TPC)) were utilized to evaluate the
      antioxidant capacity of the methanolic extracts of Terfezia boudieri Chatin,
      Boletus edulis, and Lactarius volemus. The reactive species scavenging activities
      of these extracts were also investigated in vitro. High contents of phenolic and
      flavonoid compounds may be the major contributors to the observed high
      antioxidant activities of these extracts. B. edulis showed the higher TAC and
      TPC; highest inhibitory effect on DPPH and on other studied reactive oxygen
      species (ROS). MAE showed obvious advantages of high extraction efficiency with
      lower solvent consumption in terms of high antioxidant capacity/activity of
      extracts achieved within the shortest time.

PMID- 24679788
TI  - Optimization of enzymatic hydrolysis conditions for extraction of pectin from
      rapeseed cake (Brassica napus L.) using commercial enzymes.
AB  - The aims of this study were to extract pectin from rapeseed cake (RSC) by
      enzymatic hydrolysis using commercial enzymes (Celluclast and Alcalase) and to
      investigate the effects of different reaction conditions, such as enzymatic
      hydrolysis time, enzyme-RSC ratio, and Celluclast-Alcalase ratio, on the
      degradation of RSC and pectin yield. RSC was treated using a combined extraction
      process that consisted of a fat removal process, enzymatic hydrolysis, and
      isopropanol/ethanol precipitation. After the fat removal process and enzymatic
      hydrolysis, defatted-RSC was suitably decomposed, and the loss of liberated
      reducing sugars was minimized when the hydrolysis condition reached a hydrolysis
      time of 270 min or an enzyme-RSC ratio of 1:50. Based on these results, various
      Celluclast-Alcalase ratios were applied. Alcalase led to the destruction of
      protein-carbohydrate complex in defatted-RSC, whereas Celluclast cleaved some
      linkages of carbohydrate slightly. As a result, the highest pectin yield was
      6.85% at the Celluclast-Alcalase ratio of 1:4.

PMID- 24679789
TI  - Development of a novel method for hot-pressure extraction of protein from chicken
      bone and the effect of enzymatic hydrolysis on the extracts.
AB  - To investigate the hot-pressure extraction of protein from chicken bone (CB),
      chicken bone extracts (CBE) was prepared from CB by heating at 130+/-0.5  degrees
      C for 120 min, followed by filtration, standing, defatting, and concentration.
      Effects of enzymatic hydrolysis on the properties of hydrolysates were examined.
      Results showed CBE contained 25.59% of protein, and showed a desirable value of
      protein digestibility-corrected amino acid score for adult. The total amino acid
      (AA) content of CBE is 21.99%, among which 40.62% and 54.66% are essential and
      fresh AA, respectively. Forty kinds of volatile compounds were identified after
      24 h of hydrolysis, with 2,3,5-trimethylpyrazine as the key flavor compound.
      After 8 h of hydrolysis of CBE, the content of small MW of peptides (400-1000 Da)
      increased by 74 times compared with that of 1 h. CBE and its hydrolysates
      demonstrate a new kind of potential suitable nutritional supplement in various
      foods.

PMID- 24679790
TI  - Peptides in common bean fractions inhibit human colorectal cancer cells.
AB  - The aim of this study was to characterize peptides present in common bean non
      digestible fractions (NDF) produced after enzymatic digestion and determine their
      antiproliferative action on human colorectal cancer cells. Five NDF peptides
      represented 70% of total protein (GLTSK, LSGNK, GEGSGA, MPACGSS and MTEEY) with
      antiproliferative activity on human colon cancer cells. Based on the
      antiproliferative effect, HCT116 cell line was most sensitive to bean Azufrado
      Higuera (IC50=0.53 mg/ml) and RKO to Bayo Madero (IC50=0.51 mg/ml) peptide
      extracts. Both cultivars increased significantly (p<0.05) the expression of p53
      in HCT116 by 76% and 68%, respectively. Azufrado Higuera modified the expression
      of cell cycle regulation proteins p21 and cyclin B1. Bayo Madero modified the
      expression of mitochondrial activated apoptotic proteins BAD, cytC, c-casp3,
      Survivin, BIRC7. Results suggest that peptides present in common bean NDF
      contributed to the antiproliferative effect on human colorectal cancer cells by
      modifying molecules involved in either cell cycle arrest or apoptosis.

PMID- 24679791
TI  - Chemical studies on curuba (Passiflora mollissima (Kunth) L. H. Bailey) fruit
      flavour.
AB  - The odour-active volatiles of curuba fruit (Passiflora mollissima (Kunth) L. H.
      Bailey) were isolated by solvent assisted flavour evaporation (SAFE). GC-O and GC
      MS analyses identified linalool, hexyl acetate, 1,8-cineole, and butyl acetate as
      key aroma compounds of this fruit. Other odorants relevant because of their
      contribution to the overall aroma were: 2-methylpropyl acetate, (Z)-3-hexen-1-ol,
      and (Z)-3-hexenyl acetate. Sulphur compounds, 3-sulfanylhexyl acetate and
      methional, were reported here for first time as odour-active volatiles in curuba.
      By HPLC-ESI-MS analyses of glycosidic mixtures and GC-MS analyses of volatiles
      released enzymatically with a glucosidase, (Z)-3-hexenyl beta-D-glucopyranoside
      and linalyl beta-D-glucopyranoside were identified as aroma precursors in P.
      mollissima fruit. Thermal treatment of the glycosidic mixture at native pH of
      fruit gave furanoid cis- and trans-linalool oxides, as well as, alpha-terpineol,
      compounds that exhibit flowery odour notes. Biogenic relationships among odour
      active volatiles and their glycosidic precursors were also proposed.

PMID- 24679792
TI  - Binding of carbonyl flavours to canola, pea and wheat proteins using GC/MS
      approach.
AB  - Interactions of homologous aldehydes (hexanal, heptanal, and octanal) and ketones
      (2-hexanone, 2-heptanone, and 2-octanone) to salt and alkaline-extracted canola
      and pea proteins and commercial wheat gluten were studied using GC/MS. Long-chain
      aldehyde flavours exhibited higher binding affinity, regardless of protein type
      and isolation method. Salt-extracted canola protein isolates (CPIs) revealed the
      highest binding capacity to all aldehydes followed by wheat gluten and salt
      extracted pea protein isolates (PPIs), while binding of ketone flavours decreased
      in the order: PPIs>wheat gluten>CPIs. Two aldolisation products, 2-butyl-2
      octenal and 2-pentyl-2-nonenal, were detected from the interactions between CPIs
      with hexanal and heptanal, respectively. Protein thermal behaviour in the
      presence of these compounds was analysed by differential scanning calorimeter,
      where decreased DeltaH inferred potential conformational changes due to partial
      denaturation of PPIs. Compared to ketones, aldehyde flavours possessed much
      higher "unfolding capacity" (lower DeltaH), which accounted for their higher
      binding affinities. 

PMID- 24679793
TI  - Effect of single-, dual-, and triple-retrogradation treatments on in vitro
      digestibility and structural characteristics of waxy wheat starch.
AB  - The effects of single-retrogradation (SR), dual-retrogradation (DR) and triple
      retrogradation (TR) treatments on in vitro digestibility and structural
      characteristics of waxy wheat starch were investigated. The yield of slowly
      digestible starch in a DR-treated starch with retrogradation time interval of 48
      h reached a maximum of 44.41%. The gelatinization temperature range and
      gelatinization enthalpy of DR-treated starch samples were the lowest. Moreover,
      compared with native starch, X-ray diffraction patterns of treated starches were
      altered from A-type to B-type and relative crystallinity was significantly
      decreased, which was responsible for the interaction between amylose-amylose
      and/or amylose-amylopectin chains that may generate more imperfect structures.
      Scanning electron micrographs revealed that compared with SR-treated and TR
      treated starches, the surface of DR-treated starch with a retrogradation time
      interval of 48 h exhibited a net-like structure with numerous cavities. These
      results suggest that structural changes of waxy wheat starch by cycled
      retrogradation treatment significantly affect digestibility, and DR treatment can
      be used for preparing SDS product.

PMID- 24679794
TI  - Verification of presence of caprolactam in sprouted achenes of Fagopyrum
      esculentum Moench and its influence on plant phenolic compound content.
AB  - The presence of caprolactam, a precursor of Nylon-6, among those synthetic
      polymers which are widely-spread throughout the environment, could be the reason
      for its being found in plants. The aim of this work was to confirm the previously
      described presence of caprolactam in dry and sprouted achenes, as well as in
      achene exudates of common buckwheat (Fagopyrum esculentum Moench). When the
      lyophilized sprouted and dry buckwheat achenes, along with exudates from growth
      experiments, with caprolactam-free medium were analysed by HPLC, no caprolactam
      was found. After addition of caprolactam into the growth medium, we confirmed the
      uptake of caprolactam in the lyophilized sprouted buckwheat achenes. The uptake
      of caprolactam is also a function of light conditions during the growth
      experiments. Caprolactam also inhibits the content of phenolic compounds;
      especially rutin, vitexin, isovitexin, orientin, and homoorientin in buckwheat
      plants. 

PMID- 24679795
TI  - Effect of fining on the colour and pigment composition of young red wines.
AB  - This work aimed to evaluate the effect of four fining agents on the colour and
      pigment composition of red wines of Tannat. The wines were analysed 15 days after
      fining and immediately after separation of sediments and bottling. Colour was
      evaluated by spectrophotometry and polyphenols were analysed by spectrophotometry
      and HPLC-DAD. The colour intensity of wine was significantly decreased by
      bentonite and egg albumin. The most remarkable effects on wine phenolic
      composition were produced by bentonite and gelatin, which significantly decreased
      anthocyanin and tannin concentrations, respectively. Results show that each
      fining agent has very different impact on the wine attributes, and their effects
      depended as well on the composition of the clarified wine. The use of non
      traditional agents of fining, as vegetable proteins, may have less impact on the
      colour and anthocyanin content of red wines.

PMID- 24679796
TI  - Natural occurrence of deoxynivalenol and zearalenone in wheat from Jiangsu
      province, China.
AB  - A three-year (2010-2012) survey was conducted to assess the prevalence and
      concentrations of deoxynivalenol (DON) and zearalenone (ZEN) in wheat from
      several regions of Jiangsu province, China, which are heavily impacted by
      Fusarium head blight. A total of 180 wheat samples were obtained from the
      infected fields that spread 21 counties. DON and ZEN levels were determined by
      liquid chromatography-mass spectrometry (LC-MS/MS). DON was found in 74.4% of
      samples at levels ranging from 14.52 to 41157.13 MUg/kg (mean 488.02 MUg/kg),
      while ZEN was found in 12.8% of samples at levels ranging from 10.13 to 3048.88
      MUg/kg (mean 73.04 MUg/kg). In years and regions of higher rainfall, DON and ZEN
      levels were higher in samples. These results are necessary to take a vigilant
      attitude to prevent human intake of trichothecenes and protect human's health
      from the risk of exposure to these toxins.

PMID- 24679797
TI  - Effect of temperature towards lipid oxidation and non-enzymatic browning
      reactions in krill oil upon storage.
AB  - The main objective of this study was to investigate the effect of temperature
      towards lipid oxidation and non-enzymatic browning reactions in krill oil upon
      storage. Krill oil was incubated at two different temperatures (20 and 40 
      degrees C) for 28 or 42 days. The oxidative stability of krill oil was assessed
      by peroxide value and anisidine value, measurement of lipid derived volatiles,
      lipid classes and antioxidants. The non-enzymatic browning reactions were
      assessed through the measurement of pyrroles, free amino acids content and
      Strecker-derived volatiles. The increase of incubation temperature firstly
      increased the lipid oxidation in krill oil and subsequently the non-enzymatic
      browning reactions. The occurrence of these reactions was most likely due to the
      reaction between alpha-dicarbonyl or carbonyl compounds with amino acids or
      ammonia. In addition to tocopherol and astaxanthin esters, the formation of
      pyrroles might help to protect the krill oil against lipid oxidation.

PMID- 24679798
TI  - Comparison of extraction methods for analysis of citrinin in red fermented rice.
AB  - There is no standard method for the extraction and analysis of citrinin in red
      fermented rice (RFR). In the study, five extraction methods were compared for
      their efficiency to analyse citrinin in RFR by HPLC-FLD (reversed phase high
      performance liquid chromatography with fluorescence detection), including, (1)
      ultrasonic extraction with EW solution (ethanol:water, 7:3, v/v); (2) ultrasonic
      extraction with TEF solvent mixtures (toluene:ethyl acetate:formic acid, 7:3:1,
      v/v); (3) shaking extraction with EW; (4) shaking extraction with EF solvent
      mixtures (ethyl acetate:formic acid, 1:1, v/v); (5) shaking combined with
      ultrasonic extraction in EW. Comparison of chromatograms of citrinin by HPLC-FLD
      with different extraction methods revealed that EW was the best extraction
      solvent. It was also found that shaking combined with ultrasonic extraction in EW
      was the most efficient extraction method to extract citrinin from RFR for
      qualitative and quantitative analysis. 

PMID- 24679799
TI  - A modified QuEChERS method for simultaneous determination of flonicamid and its
      metabolites in paprika using tandem mass spectrometry.
AB  - A modified quick, easy, cheap, effective, rugged and safe (QuEChERS) acetate
      buffered sample preparation method was developed to improve extraction recovery
      of flonicamid and its two metabolites (4-trifluoromethylnicotinic acid and N-(4
      trifluoromethylnicotinoyl)glycine) in paprika followed by analysis using tandem
      mass spectrometry. Acidified acetonitrile (containing 5% acetic acid) was used as
      an extraction solvent and partitioning was carried out using sodium chloride. The
      extract was then cleaned up using C18. The linearity over a concentration range
      of 0.005-1 MUg/mL was good with a determination coefficient (R(2))>0.9997.
      Recovery at three different fortification levels was 82.2-101.7% with a relative
      standard deviation <10 for all analytes. The limit of quantitation of 0.01 mg/kg
      was quite lower than the maximum residue level set by the Korea Food and Drug
      Administration (2mg/kg). The method was successfully applied to determine
      flonicamid and its metabolites from field incurred samples. The undulating
      residue pattern observed for the parent analyte together with its metabolites
      could explain the movement behavior of systemic pesticides into plants over time.

PMID- 24679800
TI  - Application of a voltammetric electronic tongue and near infrared spectroscopy
      for a rapid umami taste assessment.
AB  - The relationships between sensory attribute and analytical measurements,
      performed by electronic tongue (ET) and near-infrared spectroscopy (NIRS), were
      investigated in order to develop a rapid method for the assessment of umami
      taste. Commercially available umami products and some aminoacids were submitted
      to sensory analysis. Results were analysed in comparison with the outcomes of
      analytical measurements. Multivariate exploratory analysis was performed by
      principal component analysis (PCA). Calibration models for prediction of the
      umami taste on the basis of ET and NIR signals were obtained using partial least
      squares (PLS) regression. Different approaches for merging data from the two
      different analytical instruments were considered. Both of the techniques
      demonstrated to provide information related with umami taste. In particular, ET
      signals showed the higher correlation with umami attribute. Data fusion was found
      to be slightly beneficial - not so significantly as to justify the coupled use of
      the two analytical techniques. 

PMID- 24679801
TI  - The extent of ovalbumin in vitro digestion and the nature of generated peptides
      are modulated by the morphology of protein aggregates.
AB  - The impact of heat-induced aggregation on the extent of ovalbumin digestion and
      the nature of peptides released was investigated using an in vitro digestion
      model. The extent of hydrolysis, estimated by the disappearance of intact
      ovalbumin and the appearance of soluble peptides, was greater for the linear
      aggregates as compared to the spherical aggregates. The latter result may be due
      to differences in the surface area to volume ratio of the aggregates, or the
      degree of unfolding of the proteins during aggregate preparation. Peptide
      identification using LC-MS/MS highlighted that ovalbumin aggregation rendered a
      number of peptide bonds accessible to digestive proteases which were not
      accessible in native ovalbumin. Moreover, the peptide bonds that were cleaved
      appeared to be specific depending on the morphology of the aggregates. This work
      illustrates the links existing between food structure and their breakdown during
      the digestive process. Such quantitative and qualitative differences may have
      important nutritional consequences. 

PMID- 24679802
TI  - Mechanisms of folate losses during processing: diffusion vs. heat degradation.
AB  - Though folates are sensitive to heat treatments, leaching appears to be a major
      mechanism involved in folate losses in vegetables during processing. The aim of
      our study was to study folate diffusivity and degradation from spinach and green
      beans, in order to determine the proportion of each mechanism involved in folate
      losses. Folate diffusivity constant, calculated according to Fick's second law
      (Crank, 1975), was 7.4*10(-12) m(2)/s for spinach and 5.8*10(-10) m(2)/s for
      green beans, which is the same order of magnitude as for sugars and acids for
      each vegetable considered. Folate thermal degradation kinetics was not monotonous
      in spinach and green beans especially at 45  degrees C and did not follow a first
      order reaction. The proportion of vitamers changed markedly after thermal
      treatment, with a better retention of formyl derivatives. For spinach, folate
      losses were mainly due to diffusion while for green beans thermal degradation
      seemed to be preponderant.

PMID- 24679803
TI  - Cultivar difference in physicochemical properties of starches and flours from
      temperate rice of Indian Himalayas.
AB  - Starch and flour of seven temperate rice cultivars grown in Himalayan region were
      evaluated for composition, granule structure, crystallinity, Raman spectrometry,
      turbidity, swelling power, solubility, pasting properties and textural
      properties. The rice cultivars showed medium to high amylose content for starch
      (24.69-32.76%) and flour (17.78-24.86%). SKAU-382 showed the highest amount of
      amylose (32.76%). Rice starch showed polyhedral granule shapes and differences in
      their mean granule size (2.3-6.5 MUm) were noted among the samples. The starch
      and flour samples showed type A-pattern with strong reflection at 15, 18, and 23.
      Pasting profile and textural analysis of rice starch and flour showed that all
      the cultivars differences, probably due to variation in amylose content. The
      present study can be used for identifying differences between rice genotypes for
      starch and flour quality and could provide guidance to possible industries for
      their end use.

PMID- 24679804
TI  - Effects of different treatments on the antioxidant properties and phenolic
      compounds of rice bran and rice husk.
AB  - We investigated the changes of antioxidant activity and bioactive compounds in
      bran, rice husk and ground rice husk after three different treatments, namely hot
      air, far-infrared radiation (FIR), and cellulase, compared with raw samples.
      Overall, FIR-treated group showed a higher DPPH radical scavenging activities,
      ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) than
      did hot-air and cellulase treatments for all samples. A significant increase in
      alpha- and gamma-tocopherols was found in FIR irradiated rice bran compared to
      raw bran, while alpha- and gamma-tocopherols in hot-air and cellulase treated
      rice bran were remained unchanged. Cellulase significantly increased the amount
      of vanillic acid; however a dramatic decrease of ferulic acid was observed. The
      contents of gamma-oryzanol in cellulase treated ground rice husk were
      significantly increased. Decreasing particle size in the husk was found to work
      positively for enhancing antioxidant activities, gamma-oryzanol and phenolic
      compounds. 

PMID- 24679807
TI  - Evaluating the effects of amylose and Concord grape extract powder substitution
      on physicochemical properties of wheat flour extrudates produced at different
      temperatures.
AB  - In this study, the effects of Concord grape extract powder (CGEP), high-amylose
      starch, and their combinations on quality parameters of extruded products were
      investigated by substituting wheat flour with those ingredients in the
      formulations. Physical quality parameters such as water absorption, bulk density,
      diametric expansion and hardness of extrudates were evaluated in addition to
      thermal properties, pasting properties and resistant starch contents. Average
      values obtained for 90, 120 and 150  degrees C extrusion temperatures changed
      respectively as follows: 0.916, 0.987 and 0.467 N for hardness; 2.12, 4.07 and
      5.12 ml water/g sample for water absorption; 1.35, 2.09 and 2.51 for diametric
      expansions and 1286.6, 723.6 and 311.1 kg/m(3) for bulk densities. Extrusion
      temperature was found to have more distinct effect on physical quality parameters
      of extrudates than the substitution level of ingredients. Both CGEP and amylose
      additions negatively affected pasting properties, slightly affected resistant
      starch content and prevented gelatinization. However retardation of
      retrogradation was more evident when substitution was with CGEP alone rather than
      its combination with amylose.

PMID- 24679806
TI  - Optimisation of pressurised liquid extraction (PLE) for rapid and efficient
      extraction of superficial and total mineral oil contamination from dry foods.
AB  - Pressurised liquid extraction (PLE) represents a powerful technique which can be
      conveniently used for rapid extraction of mineral oil saturated (MOSH) and
      aromatic hydrocarbons (MOAH) from dry foods with a low fat content, such as
      semolina pasta, rice, and other cereals. Two different PLE methods, one for rapid
      determination of superficial contamination mainly from the packaging, the other
      for efficient extraction of total contamination from different sources, have been
      developed and optimised. The two methods presented good performance
      characteristics in terms of repeatability (relative standard deviation lower than
      5%) and recoveries (higher than 95%). To show their potentiality, the two methods
      have been applied in combination on semolina pasta and rice packaged in direct
      contact with recycled cardboard. In the case of semolina pasta it was possible to
      discriminate between superficial contamination coming from the packaging, and pre
      existing contamination (firmly enclosed into the matrix). 

PMID- 24679805
TI  - Electrochemical determination of estrogenic compound bisphenol F in food
      packaging using carboxyl functionalized multi-walled carbon nanotubes modified
      glassy carbon electrode.
AB  - A simple and highly sensitive electroanalytical method for the determination of
      bisphenol F (BPF) was developed, which was carried out on multi-walled carbon
      nanotubes-COOH (MWCNT-COOH) modified glassy carbon electrode (GCE) using cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV). The results showed
      that MWCNT-COOH remarkably enhanced the oxidation of BPF, which improved the
      anodic peak current of BPF significantly. The mechanism was oxidation of BPF lose
      electrons on the electrode surface via adsorption-controlled process, electrode
      reaction is the two electrons/two protons process. Under the optimised
      conditions, the oxidation peak current was proportional to BPF concentration the
      range from 0.12 to 6.01 MUg mL(-1). The detection limit was 0.11 MUg mL(-1)
      (S/N=3), and the relative standard deviation (R.S.D.) was 3.5% (n=9). Moreover,
      the MWCNT-COOH/GCE electrode showed good reproducibility, stability and anti
      interference. Therefore, the proposed method was successfully applied to
      determine BPF in food packing and the results were satisfactory.

PMID- 24679808
TI  - Analysis of the mineral composition of Italian saffron by ICP-MS and
      classification of geographical origin.
AB  - 27 Saffron spices produced in three Italian regions, Abruzzo (L'Aquila), Umbria
      and Sardinia, were analysed by inductively coupled plasma-mass spectrometry to
      test potentiality of mineral composition for geographical traceability. A linear
      discriminant analysis (LDA) based on concentrations of 12 selected elements, Li,
      B, Na, Ga, Rb, Sr, Zr, Nb, Cs, Ba, Sm, and Hf, allows more than 80% of correct
      predictions in leave-one cross-validation. Four elements (B, Na, Sr and Rb),
      identified by step-wise LDA, provide more than 90% of correct predictions.
      Moreover, saffron spices cultivated in Sardinia and Central Italy can be
      distinguished under more severe validation conditions (20% of samples in the
      prediction set). In summary, mineral composition results a promising indicator of
      saffron geographical origin. 

PMID- 24679809
TI  - Electrochemical determination of bisphenol A in plastic bottled drinking water
      and canned beverages using a molecularly imprinted chitosan-graphene composite
      film modified electrode.
AB  - Herein, a novel electrochemical sensor based on an acetylene black paste
      electrode modified with molecularly imprinted chitosan-graphene composite film
      for sensitive and selective detection of bisphenol A (BPA) has been developed.
      Several important parameters controlling the performance of the sensor were
      investigated and optimised. The imprinted sensor offers a fast response and
      sensitive BPA quantification. Under the optimal conditions, a linear range from
      8.0 nM to 1.0 MUM and 1.0 to 20 MUM for the detection of BPA was observed with
      the detection limit of 6.0 nM (S/N=3). Meanwhile, the fabricated sensor showed
      excellent specific recognition to template molecule among the structural
      similarities and coexistence substances. Furthermore, this imprinted
      electrochemical sensor was successfully employed to detect BPA in plastic bottled
      drinking water and canned beverages.

PMID- 24679810
TI  - Polyamidoamine dendrimers as off-column binding agent and in-column
      pseudostationary phase for efficient and sensitive capillary electrophoretic
      analysis of fluoroquinolones in chicken muscles.
AB  - A capillary electrophoresis method based on polyamidoamine dendrimers has been
      developed for quick and sensitive detection of moxifloxacin, gatifloxacin,
      lomefloxacin, enoxacin, ofloxacin and pazufloxacin. Increasing buffer alkalinity
      led to enhanced sensitivity, whereas the polyamidoamine-fluoroquinolone
      interactions, i.e., in-cavity hydrogen bonding/hydrophobic interaction and
      electrostatic interaction, contributed to the improvement in both separation
      efficiency and detection sensitivity. By using 1 mM polyamidoamine generation 0.5
      as binding agent in sample solution and 0.1 MUM polyamidoamine generation zero as
      pseudostationary phase to the running buffer of 5 mM sodium tetraborate at pH
      9.3, the six fluoroquinolones were baseline separated in <10 min with detection
      limits at ng/mL level. Coupled with liquid-liquid extraction, the proposed method
      was successfully applied in the determination of fluoroquinolones in chicken
      muscle samples.

PMID- 24679811
TI  - Ortho-diphenol profile and antioxidant activity of Algerian black olive
      cultivars: effect of dry salting process.
AB  - Six Algerian olive cultivars (Azeradj, Sigoise, Bouchouk, Abelout, Aberkane and
      Atefah) processed by dry salting were investigated for the total polyphenols,
      ortho-diphenol profile and antioxidant activity. The dry salting affects total
      polyphenol and o-diphenol contents with a loss rate of 6-46% and 7-50%,
      respectively, depending on the cultivar. Consequently, a decrease in the
      antioxidant activity was observed, 10-35% for the reducing power, 29-58% for the
      DPPH radical scavenging activity and 10-48% for the ferrous-chelating power.
      Among the o-diphenols identified in the salted olives, hydroxytyrosol was the
      most abundant followed by verbascoside and caffeic acid. The comparative study
      showed that Sigoise from Relizane which contains the highest levels of
      polyphenols and o-diphenols exhibits the best antioxidant activity. Our results
      suggest that in addition to the processing, the cultivar and the geographical
      origin would have a pronounced influence on both o-diphenol composition and
      antioxidant activity of olives. 

PMID- 24679812
TI  - Magnetic solid phase extraction followed by high-performance liquid
      chromatography for the determination of sulphonamides in milk samples.
AB  - A simple and effective method based on magnetic solid-phase extraction combined
      with high performance liquid chromatography was used for the determination of
      nine sulphonamides in milk samples. The extraction and cleanup via silica-based
      magnetic adsorbent dispersion in milk samples followed by the magnetic isolation
      and desorption of the analytes using NaOH-methanol. Three different magnetic
      phenyl silica adsorbents were synthesized by varying the molar ratio of
      phenyltrimethylsilane and tetramethylorthosilicate; these adsorbents were
      evaluated for sulphonamides retention in terms of their pH and degree of
      hydrophobicity. The optimal conditions were a pH of 6.0 and a magnetic:sorbent
      ratio of 2:1. Under optimal conditions, limits of detection ranging from 7 to 14
      MUg L(-1) were obtained. The method was validated according with the European
      Commision Decision 2002/657/EC. The proposed method was applied to analyse
      sulphonamides in 27 milk samples of different brands. Thirteen samples tested
      were positive for the presence of sulphonamides.

PMID- 24679813
TI  - Fast methodology of analysing major steviol glycosides from Stevia rebaudiana
      leaves.
AB  - The aim of this work is to propose an HPLC method for analysing major steviol
      glycosides as well as to optimise the extraction and clarification conditions for
      obtaining these compounds. Toward this aim, standards of stevioside and
      rebaudioside A with purities ?99.0%, commercial samples from different companies
      and Stevia rebaudiana Bertoni leaves from Paraguay supplied by Insobol, S.L.,
      were used. The analytical method proposed is adequate in terms of selectivity,
      sensitivity and accuracy. Optimum extraction conditions and adequate
      clarification conditions have been set. Moreover, this methodology is safe and
      eco-friendly, as we use only water for extraction and do not use solid-phase
      extraction, which requires solvents that are banned in the food industry to
      condition the cartridge and elute the steviol glycosides. In addition, this
      methodology consumes little time as leaves are not ground and the filtration is
      faster, and the peak resolution is better as we used an HPLC method with gradient
      elution. 

PMID- 24679814
TI  - Effect of experimental parameters in the pressurized solvent extraction of
      polyphenolic compounds from white grape marc.
AB  - A method based on pressurized solvent extraction (PSE) to determine main
      polyphenolic compounds in the grape marc obtained as a byproduct of the white
      winemaking process has been developed. As response variables in the optimisation
      process include main individual polyphenols, as well as spectrophotometric
      indexes. The optimised PSE procedure implies the use of 1 g of sample, without
      preliminary clean-up step, sea sand as dispersant, temperature of 105  degrees C,
      methanol (63%) in water as solvent, and 5 min of extraction time (2 static
      cycles). The performance of the proposed method has been assessed in terms of
      recovery (91-105%), linearity (R(2)>0.995) and precision. The applicability of
      the method was demonstrated by the analysis of bagasse samples collected from 12
      wineries located in Galicia (NW Spain). Data of the in vitro antioxidant
      activities of the PSE extracts are also discussed.

PMID- 24679815
TI  - Composition and antioxidant activity of red fruit liqueurs.
AB  - Fruits traditionally used for liqueurs are a good source of phenolic compounds
      endowed with antioxidant activity. The aim of this study was to compare the
      content of phenolic compounds and anthocyanins and the antioxidant capacity of
      liqueurs made from red fruits. The liqueurs were made from fruits of 10 species:
      chokeberry, cornelian cherry, black rose, blackcurrant, blackberry, raspberry,
      mahonia, sloe, strawberry, and sour cherry. The liqueurs from black rose,
      chokeberry, sloe and mahonia fruits contained the most of substances which react
      with the Folin-Ciocalteu reagent (671, 329, 271 and 218 mg GAE/100 mL,
      respectively) and had the highest antioxidant activity. The samples stored at a
      temperature of 30  degrees C had antioxidant activity from 3% to 11% lower than
      the fresh samples. After 6 months, anthocyanins degraded almost completely in the
      samples stored at 30  degrees C and at 15  degrees C there was from 0%
      (blackcurrant liqueurs) to 47% (sloe liqueurs) of their initial content and
      slightly more in sweet liqueurs.

PMID- 24679816
TI  - Phenolic composition, antioxidant properties, and endothelial cell function of
      red and white cranberry fruits.
AB  - The effects of phenolic constituents in red cranberry extracts (RCE) and white
      cranberry extracts (WCE) on the endothelial cell function were investigated.
      Peonidin-3-O-galactoside, cyanidin-3-O-arabinoside, and cyanidin-3-O-galactoside
      were the predominant anthocyanins characterized, whereas a procyanidin tetramer
      was the predominant proanthocyanidin identified. The antioxidant properties of
      RCE and WCE were not significantly different regardless of antioxidant assays
      (DPPH, FRAP, and TEAC) used. Both RCE and WCE induced the phosphorylation of Akt
      in vitro in human umbilical endothelial cells (HUVEC), resulting in the
      phosphorylation of endothelial nitric oxide synthase, cell migration, and tube
      formation. The enhanced phosphorylation of PI3/Akt kinase in HUVEC, endothelial
      cell wound healing, and tube formation elicited by RCE and WCE suggest that
      overall phenolic constituents rather than individual phenolic compounds within
      the cranberry matrix may be responsible for these biological effects. 

PMID- 24679817
TI  - Simultaneous determination of red and yellow artificial food colourants and
      carotenoid pigments in food products.
AB  - A method for simultaneously determining four artificial food colourants [Red Nos.
      2 (R2) and 40 (R40), Yellow Nos. 5 (Y5) and 6 (Y6)] and three carotenoids
      [lycopene, lutein, and beta-carotene] was developed. They were successfully
      separated by the developed high pressure liquid chromatography (HPLC) method
      combined with a photo diode array detector. The detection limit (at signal to
      noise>4) was from the lowest of 0.2 ng/mL for lutein to the highest of 50.0 ng/mL
      for R40. With a two-phase solvent and ultrasound-assisted extraction, the
      recoveries of the artificial and natural pigments in fifteen different types of
      food products were between 80.5-97.2% and 80.1-98.4%, respectively. This HPLC
      method with the ultrasound-assisted extraction protocol could be used as a
      sensitive and reliable analysis technique in simultaneously identifying and
      quantifying the reddish and yellowish pigments in different foods regardless of
      they are artificial food colourants or/and natural carotenoids.

PMID- 24679818
TI  - Optimised purification and characterisation of lipid transfer protein 1 (LTP1)
      and its lipid-bound isoform LTP1b from barley malt.
AB  - In beer brewing, brewers worldwide strive to obtain product consistency in terms
      of flavour, colour and foam. Important proteins contributing to beer foam are
      lipid transfer proteins (LTPs), in particular LTP1 and its lipid-bound isoform
      LTP1b, which are known to transport lipids in vivo and prevent lipids from
      destabilising the beer foam. LTP1 and LTP1b were successfully purified using only
      five purification steps with a high purified protein yield (160 mg LTP1 and LTP1b
      from 200 g barley). Circular dichroism of LTP1 and LTP1b confirmed that both
      proteins are highly tolerant to high temperatures (>90  degrees C) and are pH
      stable, particularly at a neutral to a more basic pH. Only LTP1 exhibited
      antiyeast and thermo-stable lytic activity, while LTP1b was inactive, indicating
      that the fatty acid moiety compromised the antimicrobial activity of LTP1. This
      lack in antiyeast activity and the positive foam properties of LTP1b would
      benefit beer fermentation and quality.

PMID- 24679819
TI  - Facile synthesis of the Li-rich layered oxide Li1.23Ni0.09Co0.12Mn0.56O2 with
      superior lithium storage performance and new insights into structural
      transformation of the layered oxide material during charge-discharge cycle: in
      situ XRD characterization.
AB  - In this work, the Li-rich oxide Li1.23Ni0.09Co0.12Mn0.56O2 was synthesized
      through a facile route called aqueous solution-evaporation route that is simple
      and without waste water. The as-prepared Li1.23Ni0.09Co0.12Mn0.56O2 oxide was
      confirmed to be a layered LiMO2-Li2MnO3 solid solution through ex situ X-ray
      diffraction (ex situ XRD) and transmission electron microscopy (TEM).
      Electrochemical results showed that the Li-rich oxide Li1.23Ni0.09Co0.12Mn0.56O2
      material can deliver a discharge capacity of 250.8 mAhg(-1) in the 1st cycle at
      0.1 C and capacity retention of 86.0% in 81 cycles. In situ X-ray diffraction
      technique (in situ XRD) and ex situ TEM were applied to study structural changes
      of the Li-rich oxide Li1.23Ni0.09Co0.12Mn0.56O2 material during charge-discharge
      cycles. The study allowed observing experimentally, for the first time, the
      existence of beta-MnO2 phase that is appeared near 4.54 V in the first charge
      process, and a phase transformation of the beta-MnO2 to layered Li0.9MnO2 is
      occurred in the initial discharge process by evidence of in situ XRD pattrens and
      selected area electron diffraction (SAED) patterns at different states of the
      initial charge and discharge process. The results illustrated also that the
      variation of the in situ X-ray reflections during charge-discharge cycling are
      clearly related to the changes of lattice parameters of the as-prepared Li-rich
      oxide during the charge-discharge cycles. 

PMID- 24679820
TI  - Can MALDI-TOF mass spectrometry be used with intravascular catheters?
AB  - INTRODUCTION: The use of the matrix-assisted laser desorption/ionization time of
      flight (MALDI-TOF) mass spectrometry has shown to be effective and fast in some
      clinical specimens for the identification of colonizing microorganisms. The
      objective of the study was to analyze the validity values for the prediction of
      colonization and catheter-related bloodstream infection (C-RBSI) of the MALDI-TOF
      mass spectrometry performed at all intravascular catheters that arrived in the
      microbiology laboratory. METHODS: Catheter tips (after performing the roll-plate
      technique) were tested by MALDI-TOF mass spectrometry during a period of 3
      months. The gold standard for colonization and C-RBSI were, respectively: the
      presence of >=15cfu/plate in the catheter tip culture; and the isolation of the
      same microorganism(s) in blood cultures as well as in the colonized catheter
      (during the 7days before or after catheter withdrawal). RESULTS: A total of 182
      intravascular catheters were collected. The overall colonization rate detected by
      roll-plate technique and MAL-TOF mass spectrometry was 31.9% and 32.4%,
      respectively. Overall, there were 33 (18.1%) episodes of C-RBSI. The validity
      values of the MALDI-TOF mass spectrometry for the identification of colonization
      and C-RBSI were, respectively: sensitivity (69.0%/66.7%), specificity
      (84.7%/75.2%), positive predictive value (65.6%/36.1%), and negative predictive
      value (86.8%/92.6%). Conclusion MALDI-TOF mass spectrometry could be an
      alternative diagnostic tool for ruling out C-RBSI. However, despite it showing to
      be faster than conventional culture, future studies are required in order to
      improve the pre-analytical process.

PMID- 24679821
TI  - Late prenatal dexamethasone and phenotype variations in 46,XX CAH: concerns about
      current protocols and benefits for surgical procedures.
AB  - OBJECTIVE: To describe the action of prenatal dexamethasone (PreDex) on the
      anatomy of female congenital adrenal hyperplasia (CAH) genitalia when started at
      later stages of gestation. MATERIALS AND METHODS: Our group follows a large
      cohort of French CAH patients who underwent PreDex therapy, of whom 258 were
      recently reported. Four 46,XX patients with a delayed PreDex treatment presented
      with a virilized genitalia and required surgical reconstruction. This is a
      retrospective report on genital phenotyping at the time of surgery of these four
      patients who began PreDex therapy at 8, 12, 20, and 28 weeks of gestation.
      RESULTS: Although this series is limited in number, the anatomical description of
      the length of the genital tubercle, the height of the urethra-vaginal confluence,
      and the degree of fusion of the genital folds seems to be dependent upon the
      starting date of PreDex. Most PreDex treatments prescribed up to now have covered
      the full duration of gestation. CONCLUSIONS: Our findings suggest that PreDex
      therapy could be limited to the period of the partitioning window. It is hoped
      that further prospective multicentric clinical studies will obtain ethical
      approval in order to elucidate the place and protocols of PreDex therapy in the
      management of CAH.

PMID- 24679823
TI  - Letter to the Editor Re 'Intravesical botulinum type-A toxin (Dysport(r)) in the
      treatment of idiopathic detrusor overactivity in child'.

PMID- 24679824
TI  - Commentary to 'Does bladder augmentation negatively affect renal transplant
      outcome in PUV patients?'.

PMID- 24679825
TI  - Determination of perfluorooctanoic acid and perfluorooctane sulfonate in cooking
      oil and pig adipose tissue using reversed-phase liquid-liquid extraction followed
      by high performance liquid chromatography tandem mass spectrometry.
AB  - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are two
      perfluorinated compounds (PFCs) ubiquitously present in the environment, which
      could pose potential adverse effects on human health. Contamination and presence
      of PFOA and PFOS should be eliminated or rigidly restricted in food stuffs such
      as cooking oils and lard (from pig adipose tissue). This work describes a rapid,
      simple, reliable and sensitive method for quantitative analysis of PFOA and PFOS
      in cooking oils and pig adipose tissue with liquid chromatography tandem mass
      spectrometry (LC-MS/MS). The pretreatment mainly included a one-step reversed
      phase liquid-liquid extraction using the mixture of basified water/methanol as
      the aqueous system, and dichloromethane (DCM) as the non-polar system. PFOA and
      PFOS can be successfully separated from the two lipid-rich matrices, i.e.,
      cooking oil and adipose tissue, and extracted into the aqueous system, and then
      directly analyzed with LC-MS/MS. This method was validated in terms of accuracy
      (both intra- and inter-batch), precision, recovery, linearity, sensitivity and
      applicability. The intra-batch accuracies for PFOA and PFOS in cooking oil
      samples were within 93.9-101.9% with relative standard deviation (RSD) no more
      than 10.9%, and the inter-batch accuracies were 91.2-96.2% with RSD not exceeding
      10.0%. The intra-batch accuracies of the analytes in pig adipose tissue samples
      were 102.9-113.0% with RSD of 8.8-13.1%. And the quantification ranges of PFOA
      and PFOS were 0.01-25ng/mL. This method has been applied to the analysis of PFOA
      and PFOS in real samples collected from local markets in Guangzhou, China. 

PMID- 24679826
TI  - Screening of neuraminidase inhibitors from traditional Chinese medicines by
      integrating capillary electrophoresis with immobilized enzyme microreactor.
AB  - A simple and effective neuraminidase-immobilized capillary microreactor was
      fabricated by glutaraldehyde cross-linking technology for screening the
      neuraminidase inhibitors from traditional Chinese medicines. The substrate and
      product were separated by CE in short-end injection mode within 2 min. Dual
      wavelength ultraviolet detection was employed to eliminate the interference from
      the screened compounds. The parameters relating to the separation efficiency and
      the activity of immobilized neuraminidase were systematically evaluated. The
      activity of the immobilized neuraminidase remained 90% after 30 days storage at 4
      degrees C. The immobilized NA microreactor could be continuously used for more
      than 200 runs. The Michaelis-Menten constant of neuraminidase was determined by
      the microreactor as 136.6 +/- 10.8 MUM. In addition, six in eighteen natural
      products were found as potent inhibitors and the inhibition potentials were
      ranked in the following order: bavachinin>bavachin>baicalein>baicalin>chrysin and
      vitexin. The half-maximal inhibitory concentrations were 59.52 +/- 4.12, 65.28 +/
      1.07, 44.79 +/- 1.21 and 31.62 +/- 2.04 for baicalein, baicalin, bavachin and
      bavachinin, respectively. The results demonstrated that the neuraminidase
      immobilized capillary microreactor was a very effective tool for screening
      neuraminidase inhibitors from traditional Chinese medicines.

PMID- 24679828
TI  - General retention parameters of chiral analytes in cyclodextrin gas
      chromatographic columns.
AB  - Two thermodynamic parameters - entropy (DeltaS) and enthalpy (DeltaH) - ideally
      describe the thermodynamics of how the retention of an analyte in a stationary
      phase depends on the temperature. The paper examines the conversion of an
      analyte's entropy and enthalpy into chromatographically more meaningful
      equivalents: its characteristic temperature and thermal constant. Thermodynamic
      and characteristic parameters of 29 enantiomer pairs of chiral analytes, analysed
      with four cyclodextrin stationary phases, were measured, tabulated, and
      investigated. The distribution of all newly-measured characteristic parameters
      was found to be similar to the known distribution of these parameters for some
      12,000 pairs of analytes, analysed with several stationary phases. This
      similarity suggests that the peak widths of the investigated analytes in
      temperature-programmed analyses should be generally the same as the peak widths
      of other similarly retained analytes. It also suggests that the previously-known
      optimum general heating rate (about 10 oC/tM, i.e. 10 degrees C per hold-up time)
      is also the general optimum for temperature-programmed enantioselective GC
      analyses with cyclodextrins as stationary phases. The optimum general heating
      rate corresponds to the shortest analysis time for a predetermined peak capacity.
      It can substantially differ from specific optima corresponding to the best
      separation of particular peak pairs. Theoretical prediction of these specific
      optima requires more complex non-ideal thermodynamic models, and more accurate
      measurement of the parameters involved-these topics that are outside the scope of
      this report.

PMID- 24679827
TI  - Chromatographic separation of selenium and arsenic: A potential (72)Se/(72)As
      generator.
AB  - An anion exchange method was developed to separate selenium and arsenic for
      potential utility in a (72)Se/(72)As generator. The separation of the daughter
      (72)As from the (72)Se parent is based on the relative acid-base behavior of the
      two oxo-anions in their highest oxidation states. At pH 1.5, selenate is retained
      on strongly basic anion exchange resin as HSeO4(-) and SeO4(2-), while neutral
      arsenic acid, H3AsO4, is eluted. 

PMID- 24679829
TI  - Evaluation of eligibility and recruitment in breast cancer clinical trials.
AB  - Objectives of the study were to measure recruitment rates in clinical trials and
      to identify patients, physicians or trials characteristics associated with higher
      recruitment rates. Among patients who had a clinical trial available for their
      cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical
      trial. At least one trial was proposed to 33.1% (113/341) of the eligible
      patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5%
      (68/413). In multivariate analyses, trial proposal and enrollment were lower for
      elderly patients and higher in high cancer stages. Trials from pharmaceutical
      industry had higher recruitment rates and trials testing hormonal therapy
      enrolled more patients. Breast cancer patients' accrual to a clinical trial could
      be improved by trying to systematically identify all eligible patients and
      propose a trial to those eligible and to whom the treatment is planned to be
      equivalent to the standard arm of the trial.

PMID- 24679830
TI  - Barriers and facilitators to following the Dietary Guidelines for Americans
      reported by rural, Northern Plains American-Indian children.
AB  - OBJECTIVE: The Dietary Guidelines for Americans (DGA) promote healthy dietary
      choices for all Americans aged 2 years and older; however, the majority of
      Americans do not meet recommendations. The goal of the present study was to
      identify both barriers and facilitators to adherence to DGA recommendations for
      consumption of five recommended food groups: grains (specifically whole grains),
      vegetables, fruits, meat/beans and milk (specifically reduced-fat/non-fat), among
      American-Indian children. DESIGN: Nominal group technique sessions were conducted
      to identify and prioritize children's perceived barriers and facilitators to
      following the DGA, as presented in the 'MyPyramid' consumer education icon. After
      response generation to a single question about each food group (e.g. 'What sorts
      of things make it harder (or easier) for kids to follow the MyPyramid
      recommendation for vegetables?'), children individually ranked their top five
      most salient responses. Ranked responses are presented verbatim. SETTING: A rural
      Northern Plains American-Indian reservation, USA. SUBJECTS: Sixty-one self
      selected fifth-grade children. RESULTS: Core barriers for all food groups studied
      included personal preference (i.e. 'don't like') and environmental (i.e. 'cost
      too much'; 'store is too far to get them'; 'grandma don't have'). Core
      facilitators included suggestions, i.e. 'make a garden and plant vegetables';
      'tell your friends to eat healthy'. CONCLUSIONS: Barriers and facilitators are
      dissimilar for individual food groups, suggesting that dietary interventions
      should target reduction of barriers and promotion of facilitators specific to
      individual food groups recommended by the DGA.

PMID- 24679831
TI  - Prevalence of sarcopenia in geriatric hospitalized patients.
AB  - OBJECTIVES: Sarcopenia, a common syndrome in older individuals, is characterized
      by a progressive loss of muscle mass and muscle strength. Although data exist on
      the prevalence of sarcopenia in community-dwelling older individuals and nursing
      home residents, there has been no systematic research in hospitalized older
      patients according to newly developed criteria. DESIGN: Cross-sectional study
      design. SETTING: Acute geriatric ward of a general hospital. PARTICIPANTS:
      Geriatric inpatients. MEASUREMENTS: Hand grip strength was measured with the
      Jamar dynamometer, skeletal muscle index was calculated from raw data obtained
      from the bioelectrical impedance analysis, and physical function was assessed
      with the Short Physical Performance Battery. Sarcopenia was defined according to
      the criteria of the European Working Group on Sarcopenia in Older People
      (EWGSOP). RESULTS: This study involved 198 patients from a geriatric acute ward.
      Mean age was 82.8 +/- 5.9 years and 70.2% (n = 139) of the study participants
      were women. Thirteen patients (6.6%) were defined as sarcopenic and 37 (18.7%)
      were defined as severely sarcopenic. In a group comparison, patients with
      sarcopenia had a poorer nutritional status. In a binary logistic regression
      analysis, only body mass index was associated with sarcopenia, whereas gender,
      age, length of stay, cognitive function, and self-care capacity were not.
      CONCLUSION: The prevalence of sarcopenia in geriatric hospitalized patients is
      high and does not differ from those of other older individuals. Nutritional
      status is associated with sarcopenia. The predictive value of sarcopenia
      regarding outcome for older individuals still requires evaluation.

PMID- 24679832
TI  - Dose estimation for internal organs during boron neutron capture therapy for body
      trunk tumors.
AB  - Radiation doses during boron neutron capture therapy for body-trunk tumors were
      estimated for various internal organs, using data from patients treated at Kyoto
      University Research Reactor Institute. Dose-volume histograms were constructed
      for tissues of the lung, liver, kidney, pancreas, and bowel. For pleural
      mesothelioma, the target total dose to the normal lung tissues on the diseased
      side is 5Gy-Eq in average for the whole lung. It was confirmed that the dose to
      the liver should be carefully considered in cases of right lung disease. 

PMID- 24679834
TI  - Author reply: To PMID 24084498.

PMID- 24679835
TI  - Myopia in asian subjects with primary angle closure: implications for glaucoma
      trends in East Asia.
AB  - PURPOSE: To evaluate the occurrence of myopia in Asian subjects with angle
      closure and to assess the ocular biometric parameters in these subjects. DESIGN:
      Cross-sectional study. PARTICIPANTS: We prospectively recruited 427 angle-closure
      subjects (143 primary angle-closure suspects, 75 patients with primary angle
      closure, 165 patients with primary angle-closure glaucoma, and 44 patients with
      acute primary angle closure) from a Singapore hospital. METHODS: Refractive
      status was derived from the spherical equivalent of autorefraction. A-scan
      biometry (Nidek Echoscan Ultrasound US-800; Nidek Co., Tokyo, Japan) was
      performed to obtain anterior chamber depth (ACD), axial length (AL), lens
      thickness, and vitreous cavity length (VL). Anterior segment optical coherence
      tomography was performed to measure lens vault. MAIN OUTCOME MEASURES: Refractive
      status was categorized as myopia (<=-0.50 diopter [D]), emmetropia (-0.50 to
      +0.50 D), and hyperopia (>=+0.50 D). RESULTS: The mean age +/- standard deviation
      of study subjects was 65.6 +/- 7.6 years, with most being Chinese (n = 394;
      92.3%) and women (n = 275; 64.4%). Overall, myopia was present in 94 subjects
      (22%), hyperopia was present in 222 subjects (52%), and emmetropia was present in
      111 subjects (26%). Of the 94 myopic angle-closure patients, 28 (29.8%) were
      categorized as having moderate myopia (<=-2.0 to -5.0 D) and 11 (11.7%) were
      categorized as having high myopia (<=-5.00 D). Although myopic angle-closure
      subjects had longer ALs (P<0.001) and VLs (P = 0.001) than their emmetropic and
      hyperopic counterparts, there were no significant differences in ACD (P = 0.77),
      lens thickness (P = 0.44), or lens vault (P = 0.053). CONCLUSIONS: Almost one
      quarter of angle-closure patients were myopic. Myopic angle-closure subjects had
      longer VLs and ALs, but there was no difference in ACD. With the increasing rate
      of myopia in many East Asian populations, there may be many subjects with axial
      myopia but shallow ACD and angle closure. The implication is that
      ophthalmologists should not assume that glaucoma patients who are myopic have
      open angles.

PMID- 24679836
TI  - Re: Abell et al.: anterior capsulotomy integrity after femtosecond laser-assisted
      cataract surgery (ophthalmology 2014;121:17-24).

PMID- 24679833
TI  - The pathogenesis and treatment of large granular lymphocyte leukemia.
AB  - Large granular lymphocyte (LGL) leukemia is a spectrum of rare
      lymphoproliferative diseases of T lymphocytes and natural killer cells. These
      diseases frequently present with splenomegaly, neutropenia, and autoimmune
      diseases like rheumatoid arthritis. LGL leukemia is more commonly of a chronic,
      indolent nature; however, rarely, they have an aggressive course. LGL leukemia is
      thought to arise from chronic antigen stimulation, which drives long-term cell
      survival through the activation of survival signaling pathways and suppression of
      pro-apoptotic signals. These include Jak-Stat, Mapk, Pi3k-Akt, sphingolipid, and
      IL-15/Pdgf signaling. Treatment traditionally includes immunosuppression with low
      dose methotrexate, cyclophosphamide, and other immunosuppressive agents; however,
      prospective and retrospective studies reveal very limited success. New studies
      surrounding Jak-Stat signaling suggest this may reveal new avenues for LGL
      leukemia therapeutics. 

PMID- 24679837
TI  - Determinants of the quality of life in Parkinson's disease: results of a cohort
      study from Southwest China.
AB  - BACKGROUND: The determinants of the quality of life (QoL) of patients with
      Parkinson's disease (PD) in Chinese population remain largely unknown. METHODS: A
      total of 649 PD patients from Southwest China participated in this cross
      sectional study. Non-motor Symptoms Scale (NMSS) was used to evaluate the non
      motor symptoms (NMS), whereas PD Quality of Life Questionnaire (PDQ-39) was used
      to assess the QoL of the PD patients. Multiple stepwise regression analysis was
      conducted to identify the determinants of the QoL. RESULTS: NMS, H-Y stage,
      female, disease duration, UPDRS III score, single/divorced/widowed, and motor
      complications accounted for 66.3% of the variables in the multiple regression
      analysis and were the negative determinants of the QoL. Among these variables,
      NMS and H-Y stage accounted for 46.7% and 14.5%, respectively. NMS were closely
      associated with each domain of PDQ-39. Female sex especially predicted poor
      emotional well-being and bodily discomfort, whereas single/divorced/widowed
      especially predicted poor stigma and social support of PD patients. Comorbidity,
      motor complications and rural living predicted poor mobility, activities of daily
      living and emotional well-being, respectively. CONCLUSION: Both demographic and
      disease-specific factors influence the QoL in PD patients. NMS are the strongest
      independent negative determinant of the overall QoL and closely associated with
      each domain of PDQ-39. The treatment of NMS may help to improve the QoL of PD
      patients.

PMID- 24679838
TI  - Comparative short-term effects of two thoracic spinal manipulation techniques in
      subjects with chronic mechanical neck pain: a randomized controlled trial.
AB  - Spinal Manipulation (SM) has been purported to decrease pain and improve function
      in subjects with non-specific neck pain. Previous research has investigated which
      individuals with non-specific neck pain will be more likely to benefit from SM.
      It has not yet been proven whether or not the effectiveness of thoracic SM
      depends on the specific technique being used. This double-blind randomized trial
      has compared the short-term effects of two thoracic SM maneuvers in subjects with
      chronic non-specific neck pain. Sixty participants were distributed randomly into
      two groups. One group received the Dog technique (n = 30), with the subject in
      supine position, and the other group underwent the Toggle-Recoil technique (n =
      30), with the participant lying prone, T4 being the targeted area in both cases.
      Evaluations were made of self-reported neck pain (Visual Analogue Scale); neck
      mobility (Cervical Range of Motion); and pressure pain threshold at the cervical
      and thoracic levels (C4 and T4 spinous process) and over the site described for
      location of tense bands of the upper trapezius muscle. Measurements were taken
      before intervention, immediately afterward, and 20 min later. Both maneuvers
      improved neck mobility and mechanosensitivity and reduced pain in the short term.
      No major or clinical differences were found between the groups. In the between
      groups comparison slightly better results were observed in the Toggle-Recoil
      group only for cervical extension (p = 0.009), right lateral flexion (p = 0.004)
      and left rotation (p < 0.05).

PMID- 24679839
TI  - Factors predicting development of opioid use disorders among individuals who
      receive an initial opioid prescription: mathematical modeling using a database of
      commercially-insured individuals.
AB  - BACKGROUND: Prescription drug abuse in the United States and elsewhere in the
      world is increasing at an alarming rate with non-medical opioid use, in
      particular, increasing to epidemic proportions over the past two decades. It is
      imperative to identify individuals most likely to develop opioid abuse or
      dependence to inform large-scale, targeted prevention efforts. METHODS: The
      present investigation utilized a large commercial insurance claims database to
      identify demographic, mental health, physical health, and healthcare service
      utilization variables that differentiate persons who receive an opioid abuse or
      dependence diagnosis within two years of filling an opioid prescription (OUDs)
      from those who do not receive such a diagnosis within the same time frame (non
      OUDs). RESULTS: When compared to non-OUDs, OUDs were more likely to: (1) be male
      (59.9% vs. 44.2% for non-OUDs) and younger (M=37.9 vs. 47.7); (2) have a
      prescription history of more opioids (1.7 vs. 1.2), and more days supply of
      opioids (M=272.5, vs. M=33.2; (3) have prescriptions filled at more pharmacies
      (M=3.3 per year vs. M=1.3); (4) have greater rates of psychiatric disorders; (5)
      utilize more medical and psychiatric services; and (6) be prescribed more
      concomitant medications. A predictive model incorporating these findings was
      79.5% concordant with actual OUDs in the data set. CONCLUSIONS: Understanding
      correlates of OUD development can help to predict risk and inform prevention
      efforts.

PMID- 24679840
TI  - The iatrogenic epidemic of prescription drug abuse: county-level determinants of
      opioid availability and abuse.
AB  - BACKGROUND: Opioid use and abuse in the United States continues to expand at an
      alarming rate. In this study, we examine the county-level determinants of the
      availability and abuse of prescription opioids to better understand the socio
      ecological context, and in particular the role of the healthcare delivery system,
      on the prescription drug abuse epidemic. METHODS: We use community-level
      information, data from Indiana's prescription drug monitoring program in 2011,
      and geospatial regression methods to identify county-level correlates of the
      availability and abuse of prescription opioids among Indiana's 92 counties.
      RESULTS: The findings suggest that access to healthcare generally, and to
      dentists and pharmacists in particular, increases the availability of
      prescription opioids in communities, which, in turn, is associated with higher
      rates of opioid abuse. CONCLUSIONS: The results suggest that the structure of the
      local healthcare system is a major determinant of community-level access to
      opioids adding to a growing body of evidence that the problem of prescription
      opioid abuse is, at least in part, an "iatrogenic epidemic."

PMID- 24679841
TI  - Which parenting style is more protective against adolescent substance use?
      Evidence within the European context.
AB  - BACKGROUND: This study examines whether authoritative parenting style
      (characterized by warmth and strictness) is more protective against adolescent
      substances use than authoritarian (strictness but not warmth), indulgent (warmth
      but not strictness) and neglectful (neither warmth nor strictness) parenting
      styles. Emergent research in diverse cultural contexts (mainly Southern European
      and Latin American countries) questions the fact that authoritative would always
      be the optimum parenting style. DESIGN: Multi-factorial MANOVAs. PARTICIPANTS: A
      sample of 7718 adolescents, 3774 males (48.9%), 11-19 year-olds (M=14.63 year
      olds, SD=1.9 years) from Sweden, United Kingdom, Spain, Portugal, Slovenia, and
      the Czech Republic. MEASUREMENTS: Parenting style dimensions (warmth and
      strictness) and adolescent substance use (alcohol, tobacco, and illegal drugs);
      additionally another three adolescent outcomes were also measured (self-esteem,
      school performance and personal disturbances) all of them related in the
      literature with substance use. FINDINGS: Both indulgent and authoritative
      parenting styles were associated with better outcomes than authoritarian and
      neglectful parenting in all the countries studied. Overall, our results support
      the idea that in Europe the indulgent parenting style performs as well as the
      authoritative one since adolescents' scores in the youth outcomes were equal (on
      substance use and personal disturbances) or even better (on self esteem and
      school performance) than for authoritative parenting style. CONCLUSIONS:
      Parenting styles relate to substance use and other outcomes in the same way in
      different countries explored. The so-called indulgent parenting style appears to
      be as good as the authoritative in protecting against substance abuse.

PMID- 24679842
TI  - Longevity of dental implants in type IV bone: a systematic review.
AB  - Bone quality and quantity are important factors with regard to the survival rate
      of dental implants. The aim of this study was to conduct a systematic review of
      dental implants inserted in low-density bone and to determine the survival rate
      of dental implants with surface treatments over time. A systematic review of the
      literature was undertaken by two independent individuals; the Medline/PubMed
      database was searched for the period July 1975 to March 2013. Relevant reports on
      bone quality and osseointegration of dental implants were selected. The search
      retrieved 1018 references, and after inclusion and exclusion criteria were
      applied, 19 studies were selected for review. A total of 3937 patients, who had
      received a total of 12,465 dental implants, were analyzed. The survival rates of
      dental implants according to the bone density were: type I, 97.6%; type II,
      96.2%; type III, 96.5%; and type IV, 88.8%. The survival rate of treated surface
      implants inserted in low-density bone was higher (97.1%) than that of machined
      surface implants (91.6%). Surface-treated dental implants inserted in low-density
      bone have a high survival rate and may be indicated for oral rehabilitation.
      However, more randomized studies are required to better evaluate this issue. 

PMID- 24679843
TI  - Catalytic dechlorination of 2,4-dichlorophenol by Ni/Fe nanoparticles prepared in
      the presence of ultrasonic irradiation.
AB  - In this study, nickle/iron (Ni/Fe) nanoparticles were synthesized by liquid phase
      reductive method in the presence of 20 kHz ultrasonic irradiation to improve
      nanoparticles' disparity and avoid agglomeration. The characterized results
      showed that this method has obviously modified most of the particles in term of
      sizes and specific surface areas. Meanwhile, the improved nanoscale Ni/Fe
      particles were employed for the reductive dechlorination of 2,4-dichlorophenol
      (2,4-DCP) as a function of some influential factors (Ni content, Ni/Fe
      nanoparticles dosage, reaction temperature and initial pH values) and degradation
      path. Experimental results showed that 2,4-DCP was first adsorbed by Ni/Fe
      nanoparticles, then quickly reduced to o-chlorophenol (o-CP), p-chlorophenol (p
      CP), and finally to phenol (P). The application of ultrasonic irradiation for
      Ni/Fe nanoparticles synthesis was found to significantly enhance the removal
      efficiency of 2,4-DCP. Consequently, the phenol production rates increased from
      68% (in the absence of ultrasonic irradiation) to 87% (in the presence of
      ultrasonic irradiation) within 180 min. Nearly 96% of 2,4-DCP was removed after
      300 min reaction with these optimized conditions: Ni content over Fe(0) 3 wt%,
      initial 2,4-DCP concentration 20 mg L(-1), Ni/Fe dosage 3 g L(-1), initial pH
      value 3.0, and reaction temperature 25  degrees C. The degradation of 2,4-DCP
      followed pseudo-first-order kinetics reaction and the apparent pseudo-first-order
      kinetics constant was 0.0737 min(-1). This study suggested that the presence of
      ultrasonic irradiation in the synthesis of nanoscale Ni/Fe particles could be a
      promising technique to enhance nanoparticle's disparity and avoid agglomeration.

PMID- 24679844
TI  - Metabolomics of asthma.

PMID- 24679845
TI  - Incidence of malignancy in patients with moderate-to-severe asthma treated with
      or without omalizumab.
AB  - BACKGROUND: The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical
      Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma
      (EXCELS) assessed the long-term safety of omalizumab in a clinical practice
      setting as part of a phase IV US Food and Drug Administration postmarketing
      commitment. OBJECTIVE: We sought to evaluate long-term safety in omalizumab
      treated and nonomalizumab-treated patients. Primary outcome measures focused on
      assessment of malignancies. METHODS: EXCELS was a prospective observational
      cohort study in patients (>=12 years of age) with moderate-to-severe allergic
      asthma. There were 2 cohorts: omalizumab (taking omalizumab at baseline) and
      nonomalizumab (no history of omalizumab treatment). Primary outcomes included all
      confirmed, incident, study-emergent primary malignancies (malignancies),
      including and excluding nonmelanoma skin cancer (NMSC); all malignancies were
      externally adjudicated. RESULTS: The omalizumab cohort had a higher proportion of
      patients with severe asthma compared with the nonomalizumab cohort (50.0% vs
      23.0%). Median follow-up was approximately 5 years for both cohorts. Crude
      malignancy rates were similar in the omalizumab and nonomalizumab cohorts, with a
      rate ratio of 0.84 (95% CI, 0.62-1.13) for all malignancies and 0.98 (95% CI,
      0.71-1.36) for all malignancies excluding NMSC. Kaplan-Meier plots of time to
      first confirmed study-emergent primary malignancy were similar for the 2
      treatment cohorts. Cox proportional hazards modeling, adjusting for confounders
      and risk factors, resulted in a hazard ratio (omalizumab vs nonomalizumab) of
      1.09 (95% CI, 0.87-1.38) for all malignancies and 1.15 (95% CI, 0.83-1.59) for
      all malignancies excluding NMSC. CONCLUSION: Results from EXCELS suggest that
      omalizumab therapy is not associated with an increased risk of malignancy.

PMID- 24679847
TI  - Reply: To PMID 24369803.

PMID- 24679846
TI  - Immunodeficiency and disseminated mycobacterial infection associated with
      homozygous nonsense mutation of IKKbeta.

PMID- 24679848
TI  - [Acoustic voice analysis using the Praat program: comparative study with the Dr.
      Speech program].
AB  - INTRODUCTION AND OBJECTIVES: The European Laryngological Society (ELS) basic
      protocol for functional assessment of voice pathology includes 5 different
      approaches: perception, videostroboscopy, acoustics, aerodynamics and subjective
      rating by the patient. In this study we focused on acoustic voice analysis. The
      purpose of the present study was to correlate the results obtained by the
      commercial software Dr. Speech and the free software Praat in 2 fields: 1. Narrow
      band spectrogram (the presence of noise according to Yanagihara, and the presence
      of subharmonics) (semi-quantitative). 2. Voice acoustic parameters (jitter,
      shimmer, harmonics-to-noise ratio, fundamental frequency) (quantitative).
      MATERIAL AND METHODS: We studied a total of 99 voice samples from individuals
      with Reinke's oedema diagnosed using videostroboscopy. One independent observer
      used Dr. Speech 3.0 and a second one used the Praat program (Phonetic Sciences,
      University of Amsterdam). The spectrographic analysis consisted of obtaining a
      narrow-band spectrogram from the previous digitalised voice samples by the 2
      independent observers. They then determined the presence of noise in the
      spectrogram, using the Yanagihara grades, as well as the presence of
      subharmonics. As a final result, the acoustic parameters of jitter, shimmer,
      harmonics-to-noise ratio and fundamental frequency were obtained from the 2
      acoustic analysis programs. RESULTS: The results indicated that the sound
      spectrogram and the numerical values obtained for shimmer and jitter were similar
      for both computer programs, even though types 1, 2 and 3 voice samples were
      analysed. CONCLUSIONS: The Praat and Dr. Speech programs provide similar results
      in the acoustic analysis of pathological voices.

PMID- 24679849
TI  - Relative validity of an FFQ for pre-school children in the mother-child 'Rhea'
      birth cohort in Crete, Greece.
AB  - OBJECTIVE: To examine the relative validity of an FFQ based on parental report
      for pre-school children in the mother-child 'Rhea' birth cohort. DESIGN: The
      children's mothers completed an FFQ that referred to the children's dietary
      intake for the previous year by telephone interview. Mothers completed also three
      food records, two on weekdays and one on a weekend day. Spearman correlation
      coefficients were calculated for the energy-adjusted values. Weighted kappa
      statistics (kappa(w)) and the Bland-Altman technique were used to test the degree
      of agreement between the two dietary methods. SETTING: Heraklion, Crete, Greece,
      2011-2012. SUBJECTS: A total of ninety-nine mothers (corresponding to fifty-one
      boys and forty-eight girls) participated in the validation study. RESULTS: The
      mean and median values of all food group and nutrient intakes did not differ
      significantly between the two dietary methods. Overall, fair agreement was
      observed between the FFQ and the food records for ranking participants based on
      their intake, with kappa(w) ranging from 0.21 to 0.40 for most foods and
      nutrients. On average, 88 % of participants were classified into the same or
      adjacent tertiles for nutrient and food group intakes by both dietary methods.
      The degree of agreement was also confirmed by the visual examination of the Bland
      Altman plots. CONCLUSIONS: The study indicates that the Rhea 4 years FFQ is a
      relatively accurate tool for assessing habitual food group and nutrient intakes
      among pre-school children in Crete, Greece.

PMID- 24679850
TI  - Effect of articulatory rehabilitation after oral cancer surgery on higher brain
      activation.
AB  - The present study aimed to verify the importance of postoperative articulatory
      rehabilitation in patients with oral cancer and to clarify the neurological
      changes underlying articulatory functional recovery. A longitudinal assessment of
      oral function and accompanying brain activity was performed using non-invasive
      functional magnetic resonance imaging (fMRI). We assessed 13 patients with
      cancers of the tongue and oral floor before and after ablative surgery.
      Articulatory function was assessed preoperatively and postoperatively using a
      conversation intelligibility test and the Assessment of Motor Speech for
      Dysarthria test. Patients also performed a verbal task during fMRI scans. The
      assessments were then repeated after the patients had undergone 4-6 months of
      articulatory rehabilitation therapy. Compared to pretreatment levels,
      articulatory rehabilitation resulted in a significant increase in activation in
      the supplementary motor cortex, thalamus, and cingulate cortex. The present study
      offers a quantitative assessment of the effects of speech rehabilitation by
      investigating changes in brain activation sites. 

PMID- 24679851
TI  - Does low-level laser therapy decrease swelling and pain resulting from
      orthognathic surgery?
AB  - Low-level laser therapy (LLLT) could be an alternative for the treatment of
      swelling and pain after orthognathic surgery, but there is a paucity of data in
      the literature on the effects of its use. This study verified the efficacy of an
      LLLT protocol to reduce swelling and pain after orthognathic surgery. Ten healthy
      patients who underwent a bilateral sagittal split with Le Fort I osteotomy were
      randomly selected for this study. The LLLT protocol consisted of intraoral and
      extraoral application to one side of the face after surgery (irradiated side);
      application to the other side was simulated (non-irradiated side). The irradiated
      and non-irradiated sides were compared regarding the swelling coefficient and
      were assessed for pain using a visual analogue scale. There were no significant
      differences between the irradiated and non-irradiated sides regarding swelling
      and pain in the immediate postoperative assessment. Swelling decreased
      significantly on the irradiated side in the postoperative assessments on days 3,
      7, 15, and 30. Self-reported pain was less intense on the irradiated side at the
      24-h (1.2 vs. 3.4) and 3-day (0.6 vs. 2.1) assessments, but at 7 days after
      surgery neither side showed pain. This LLLT protocol can improve the tissue
      response and reduce the pain and swelling resulting from orthognathic surgery. 

PMID- 24679852
TI  - Long-term evaluation of swallowing function before and after sagittal split ramus
      osteotomy.
AB  - The aim of this study was to determine whether mandibular setback by sagittal
      split ramus osteotomy (SSRO) influences swallowing function. The subjects were 14
      patients with skeletal class III malocclusions who underwent setback surgery by
      SSRO. Morphological changes were studied on cephalograms, and swallowing function
      was evaluated by videofluorography before the operation (T0) and at 7-10 days
      (T1), 3 months (T2), and 6 months (T3) after surgery. The angle between nasion,
      sella, and hyoid bone (HSN) and the sella-hyoid distance had increased
      significantly at T1. The hyoid bone returned to the preoperative position at T2.
      There were no significant changes in the oropharyngeal space at any time. On
      videofluorographic assessment, lingual movement, soft palate movement, and
      epiglottic movement had decreased at T1, but all patients recovered at T2. The
      oral transit time was significantly longer at T1 than at T0. Our results confirm
      that SSRO influences swallowing function. Swallowing function appears to
      stabilize by 3 months after surgery. 

PMID- 24679853
TI  - Epidermoid cysts of the rumen in a Holstein-Friesian steer.
AB  - Epidermoid cysts were identified in the rumen of a 2-year-old Holstein-Friesian
      steer. Small nodules (<4 mm diameter) filled with paste-like, friable, white
      material were scattered in the rumen wall. Microscopically, the nodules were
      located in the submucosal connective tissue and comprised of cysts lined by
      stratified squamous epithelium surrounding keratin debris, exhibiting features
      identical to those of epidermoid cysts. The cysts were surrounded by chronic
      inflammation. The ruminal mucosa contained vesicles or cystic cavities filled by
      inflammatory exudate, in addition to empty cystic spaces lined by flattened
      endothelial cells, which were possibly of lymphatic origin. The development of
      these epidermoid cysts might have resulted from implantation of exfoliated
      squamous epithelial cells from damaged ruminal epithelium into the submucosal
      connective tissue, although the precise aetiology of this anomaly remains to be
      defined.

PMID- 24679854
TI  - Heat shock protein 90 is associated with hyperplasia and neoplastic
      transformation of canine prostatic epithelial cells.
AB  - Heat shock protein 90 (HSP90) is a molecular chaperone that regulates critical
      signalling proteins of cancer development and progression. Abnormal levels of
      HSP90 have been observed in human prostatic carcinoma (PC), with prognostic and
      therapeutic implications. Since spontaneously arising canine PC is a valuable
      model for the human disease, the aim of this study was to evaluate the
      immunohistochemical expression of HSP90 in two normal canine prostates, 17 canine
      prostates with benign prostatic hyperplasia (BPH) and five canine prostates with
      PC. HSP90 was expressed in the cytoplasm of epithelial cells in all samples, with
      a significant increase in labelled cells in PCs. Nuclear labelling was observed
      occasionally in normal tissue, but was increased in BPH and PC. HSP90
      immunoreactivity in preneoplastic lesions (proliferative inflammatory atrophy and
      prostatic intraepithelial neoplasia) was similar to that in PCs. Increased HSP90
      expression in canine PCs suggests the involvement of this molecule in
      carcinogenesis and tumour progression, supporting HSP90 as a potential target for
      therapeutic intervention. 

PMID- 24679855
TI  - Verminous pneumonia and enteritis due to hyperinfection with Aelurostrongylus
      abstrusus in a kitten.
AB  - Severe infestation with Aelurostrongylus abstrusus was identified in the lungs
      and small intestine of a 2-month-old kitten that died due to verminous pneumonia
      and enteritis. On clinical examination, the kitten had dyspnoea, pneumonia,
      pleural effusion, ascites and diarrhoea. An interstitial pattern was evident
      radiographically in the lungs. The kitten died before treatment could be
      instituted. On gross and histopathological examination, there was severe
      interstitial pneumonia and large numbers of A. abstrusus eggs and larvae were
      present in alveoli, together with fewer adult nematodes in small bronchioles. The
      mucosa of the small intestine was invaded by large numbers of A. abstrusus
      larvae. The findings were consistent with a hyperinfection syndrome due to A.
      abstrusus. 

PMID- 24679856
TI  - Will omics help to cure the flu?
AB  - Influenza virus infections are still a major burden to mankind and our antiviral
      arsenal against these pathogens is limited. The cellular responses to infection
      might provide novel targets for intervention strategies. Josset et al. combined
      comparative transcriptome analysis with literature-based prediction tools for in
      silico identification of novel host-directed drugs. 

PMID- 24679857
TI  - The effects of different core-shell structures on the electrochemical
      performances of Si-Ge nanorod arrays as anodes for micro-lithium ion batteries.
AB  - Connected and airbag isolated Si-Ge nanorod (NR) arrays in different
      configurations have been fabricated on wafer scale Si substrates as anodes in
      micro-lithium ion batteries (LIBs), and the impacts of configurations on
      electrochemical properties of the electrodes were investigated experimentally and
      theoretically. It is demonstrated that the Si inner cores can be effectively
      protected by the connected Ge shells and contribute to the enhanced capacity by
      ~68%, derived from an activation process along with the amorphization of the
      crystalline lattice. The first-principles calculations further verify the smaller
      forces on the Si layers at the atomic level during the restricted volume
      expansion with the covering of Ge layers. This work provides general guidelines
      for designing other composites and core-shell configurations in electrodes of
      micro-LIBs to accomplish higher capacities and longer cycle lives. 

PMID- 24679858
TI  - Editorial comment.

PMID- 24679859
TI  - Editorial comment.

PMID- 24679860
TI  - Editorial comment.

PMID- 24679862
TI  - Editorial comment.

PMID- 24679861
TI  - VURD syndrome--does it really preserve long-term renal function?
AB  - PURPOSE: VURD (posterior urethral valves, unilateral vesicoureteral reflux and
      renal dysplasia) syndrome is the combination of persistent unilateral
      vesicoureteral reflux associated with an ipsilateral dysplastic, poorly
      functioning kidney in patients with posterior urethral valves. It was postulated
      that this syndrome may result in preservation of long-term renal function due to
      a pressure release pop-off mechanism. We determined the effects of VURD long-term
      renal outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of
      boys diagnosed with posterior urethral valves between 1983 and 2009 at a single
      pediatric tertiary hospital. Patients were divided into those with and those
      without VURD syndrome. The outcome of interest was renal impairment, defined as
      stage 3 or greater chronic kidney disease (glomerular filtration rate less than
      60 ml/min/1.73 m(2)). RESULTS: We identified 89 patients, of whom 23 (26%) had
      VURD. Median followup was 77 and 57 months in the VURD and nonVURD groups,
      respectively. Seven patients (30%) with and 26 (39%) without VURD had significant
      renal impairment. Survival analysis using a Cox proportional hazard model showed
      no association between VURD and renal impairment (HR 1.05, 95% CI 0.65-1.70). The
      main predictors of renal function were the creatinine nadir and patient age at
      diagnosis. CONCLUSIONS: VURD syndrome does not seem to have a long-term
      protective effect on renal function.

PMID- 24679863
TI  - Long-term followup of a large cohort of patients with ovotesticular disorder of
      sex development.
AB  - PURPOSE: We present the followup of a large cohort of patients with ovotesticular
      disorder of sex development treated at a single tertiary center. MATERIALS AND
      METHODS: We reviewed the records of 20 patients with ovotesticular disorder of
      sex development. We retrospectively evaluated clinical and surgical
      characteristics. A prospective study was also performed, including evaluation of
      surgical results, gonadal function, sexual activity and voiding symptoms of these
      patients during adulthood. RESULTS: All patients had ambiguous genitalia,
      including 18 with a 46,XX karyotype and 2 with a 46,XX/46,XY karyotype. Gender
      assignment at birth was male in 13 patients and female in 7. Three females were
      later reassigned to the male gender. Bilateral gonadectomy was performed in 10
      patients. Testicular tissue was preserved in 8 males and ovarian tissue was
      preserved in 2 females. Average followup was 25 years (range 4 to 46). Puberty
      started spontaneously in 14 patients between ages 11 and 14 years. Seven patients
      showed spontaneous puberty after conservative gonadal surgery and 4 required
      hormonal replacement during adulthood. The most frequent complications in males
      were urethral fistula in 6 and late urethral stenosis in 3. Two patients with
      urethral stenosis had symptoms 10 years postoperatively. One female presented
      with temporary dyspareunia. In adulthood 8 males and 2 females reported sexual
      activity. All male patients reported orgasm and 2 reported ejaculation.
      CONCLUSIONS: Male gender assignment was more prevalent. Long-term followup
      revealed adequate pubertal development and sexual activity. Complications
      involving the urethra developed frequently in male patients.

PMID- 24679864
TI  - Treatment with the immunomodulator FTY720 (fingolimod) significantly reduces
      renal inflammation in murine unilateral ureteral obstruction.
AB  - PURPOSE: The S1P signaling pathway represents an important potential target for
      the modulation of tissue inflammation/injury. The immunomodulator FTY720, also
      known as fingolimod, is a potent agonist for multiple S1P receptors that was
      approved by the Food and Drug Administration to treat multiple sclerosis. We
      examined the therapeutic role of FTY720 for renal injury secondary to unilateral
      ureteral obstruction. MATERIALS AND METHODS: CB57BL/6 mice underwent a sham
      procedure or unilateral ureteral obstruction and were treated with FTY720 by
      gavage for 1, 3 and 5 days. Control groups received vehicle. Ligated and
      unligated renal tissue was examined for histopathological changes, inflammatory
      and fibrotic markers, TGF-beta1, alpha-SMA, and macrophage infiltration by
      Western blot and immunohistochemistry. Proinflammatory and profibrotic cytokines
      were profiled by quantitative reverse transcriptase-polymerase chain reaction.
      RESULTS: Pathological evaluation revealed that FTY720 treatment resulted in a
      significant reduction in inflammatory infiltration in obstructed kidneys compared
      to controls. Immunohistochemical and Western blot showed that TGF-beta1 and alpha
      SMA protein levels were similarly decreased, as was macrophage infiltration into
      the renal interstitial space, compared to untreated mice. In agreement with these
      observations quantitative reverse transcriptase-polymerase chain reaction
      revealed that inflammatory and fibrotic cytokines (MCP-1, IL-1beta, CXCL1, TNF
      alpha and TGF-beta1) were also significantly decreased in the FTY720 group.
      CONCLUSIONS: This study suggests that in a murine ureteral obstruction model
      FTY720 significantly inhibited the production of inflammatory cytokines and
      factors regulating interstitial fibrosis and extracellular matrix accumulation.
      These findings were associated with decreased evidence of renal injury on
      pathological examination, suggesting that FTY720 or related compounds may be
      valuable modulators of obstruction induced renal injury.

PMID- 24679865
TI  - Pilot randomized, placebo controlled trial to investigate the effect of
      antibiotic prophylaxis on the rate of urinary tract infection in infants with
      prenatal hydronephrosis.
AB  - PURPOSE: We determined the feasibility of a clinical trial of continuous
      antibiotic prophylaxis to prevent urinary tract infections in children with
      prenatal hydronephrosis. MATERIALS AND METHODS: We piloted a blinded, randomized,
      placebo controlled study of the urinary tract infection rate in infants with
      grades III-IV prenatal hydronephrosis at our institution between August 2010 and
      June 2013. Study exclusion criteria were grades I/II prenatal hydronephrosis,
      vesicoureteral reflux, duplication anomalies and age at randomization greater
      than 5 months. Prospectively collected feasibility data were obtained on
      eligibility, enrollment status, adherence to followup schedule, and medication
      and protocol compliance. RESULTS: Of 301 screened patients 220 (73.1%) were
      ineligible for analysis and 2 (1%) missed the randomization window. Of the
      remaining 81 (26.9%) eligible patients 46 were enrolled (56.8%), 29 refused
      (39.5%) and consent is pending in 1 (1.2%). Reasons for declining participation
      included parental preference for or against continuous antibiotic prophylaxis and
      a lack of interest in participating in clinical research. Of 46 enrolled patients
      29 (63%) completed the trial, 12 (26.1%) are still in followup and 5 (10.9%)
      withdrew. Of the 314 medication logs dispensed 263 were returned for a 95% mean
      medication compliance rate. CONCLUSIONS: Based on the results of our pilot study
      a realistic recruitment rate for this group of patients is established, making a
      definitive trial of this topic feasible. However, due to the low number of
      eligible patients multicenter collaboration is critical to address the effect of
      continuous antibiotic prophylaxis on the urinary tract infection rate in this
      population. After study enrollment high medication and followup compliance can be
      expected.

PMID- 24679866
TI  - Risk factors for febrile urinary tract infection in infants with prenatal
      hydronephrosis: comprehensive single center analysis.
AB  - PURPOSE: We assessed risk factors for urinary tract infection in children with
      prenatal hydronephrosis MATERIALS AND METHODS: We identified 376 infants with
      prenatal hydronephrosis in an institutional database. The occurrence of febrile
      urinary tract infection in the first 2 years of life was ascertained by chart
      review. Febrile urinary tract infection was defined as a positive culture from a
      catheterized urine specimen in a patient with a fever of 38.0C or greater.
      Multivariate logistic regression was used to assess gender, circumcision status,
      hydronephrosis grade, vesicoureteral reflux grade and antibiotic prophylaxis as
      predictors of the risk of urinary tract infection. RESULTS: Included in analysis
      were 277 males and 99 females. Hydronephrosis was high grade in 128 infants
      (34.0%) and vesicoureteral reflux was present in 79 (21.0%). Antibiotic
      prophylaxis was prescribed in 60.4% of patients, preferentially to females vs
      males (70.7% vs 56.7%), those with high vs low grade hydronephrosis (70.3% vs
      55.2%) and those with vs without vesicoureteral reflux (96.2% vs 50.8%). On
      multivariate analysis there was an association between high grade hydronephrosis
      and an increased risk of urinary tract infection (adjusted OR 2.40, 95% CI 1.26
      4.56). Females (adjusted OR 3.16, 95% CI 0.98-10.19) and uncircumcised males
      (adjusted OR 3.63, 95% CI 1.18-11.22) were also at higher risk than circumcised
      males. Antibiotic prophylaxis was not associated with a decreased risk of urinary
      tract infection (adjusted OR 0.93, 95% CI 0.45-1.94). CONCLUSIONS: High grade
      hydronephrosis, female gender and uncircumcised status in males are independent
      risk factors for febrile urinary tract infection in infants with prenatal
      hydronephrosis. Antibiotic prophylaxis did not reduce the risk of urinary tract
      infection in the study group.

PMID- 24679867
TI  - Editorial comment.

PMID- 24679868
TI  - Decisional regret after distal hypospadias repair: single institution prospective
      analysis of factors associated with subsequent parental remorse or distress.
AB  - PURPOSE: Hypospadias repair is a commonly performed procedure. Little is known
      about decisional regret in parents who agree to proceed with this surgical
      reconstruction. We present data on this previously underexplored issue. MATERIALS
      AND METHODS: We performed followup analysis of 100 couples prospectively
      evaluated after counseling for surgical correction of distal hypospadias in their
      son with assessment of complications and decisional regret 1 year after surgery.
      Findings were contrasted with baseline demographics, hypospadias knowledge and
      decisional conflict at the time of counseling. RESULTS: Decisional regret was
      found in 116 parents, including mild regret in 41.4% and moderate to severe
      regret in 8.6%. There was no statistically significant difference in paired
      regret analysis between mothers and fathers. Complications were strongly
      associated with decisional regret (p <0.001). On regression analysis
      postoperative complications (OR 14.7, 95% CI 1.6-131.6), parental desire to avoid
      circumcision (OR 7.4, 95% CI 1.1-49.4) and initial decisional conflict level (OR
      1.06, 95% CI 1.02-1.09) were statistically significant predictors of moderate to
      strong decisional regret. These findings remained robust after imputation
      strategies to address missing data. The impact of decisional conflict and
      preference for circumcision were significant even after excluding families who
      experienced complications. CONCLUSIONS: To our knowledge this is the first study
      demonstrating parental decisional regret after providing consent for surgical
      correction of distal hypospadias in their son. Based on the described risk
      factors efforts aimed at minimizing complications and counseling about foreskin
      preservation techniques may be prudent to ameliorate decisional regret. The novel
      association between decisional conflict and regret suggests that conflict
      assessment during counseling may help screen families at risk for postoperative
      regret.

PMID- 24679869
TI  - Cystatin C as a marker of early renal insufficiency in children with congenital
      neuropathic bladder.
AB  - PURPOSE: Due to decreased muscle mass in children with congenital neuropathic
      bladder there may be significant inaccuracy when using the creatinine based
      estimated glomerular filtration rate. Cystatin C is highly sensitive and specific
      for measuring changes in the glomerular filtration rate in children and in
      patients with muscle wasting conditions. We hypothesized that a cystatin C
      calculated glomerular filtration rate would be more sensitive than the standard
      creatinine based modified Schwartz equation to detect renal insufficiency in
      children with congenital neuropathic bladder. MATERIALS AND METHODS: We
      prospectively identified children with congenital neuropathic bladder at a
      multidisciplinary spina bifida clinic who underwent serum creatinine and serum
      cystatin C testing. Clinical history and anthropomorphic variables at the time of
      laboratory testing were catalogued. The creatinine based glomerular filtration
      rate was estimated using the modified (bedside) Schwartz formula and the cystatin
      C based rate was calculated using the Zappitelli cystatin C formula. RESULTS:
      Dual estimated glomerular filtration rate calculation was done in 69 children at
      a total of 74 patient encounters. Absolute creatinine was within age range normal
      limits in each patient, including 1 with chronic kidney disease stage 3A. The
      median creatinine based estimated glomerular filtration rate was 123 ml per
      minute/1.73 m(2) (range 58 to 229). The median cystatin C based estimated rate
      was 103 ml per minute/1.73 m(2) (range 47 to 144) for an absolute median rate
      reduction of 15.4%. Using cystatin C estimates chronic kidney disease stage was
      upgraded from stage 1 to 2 in 13 patients (18.8%). CONCLUSIONS: In children with
      neuropathic bladder the cystatin C estimated glomerular filtration rate is a
      better screening test for early renal insufficiency that is not detected by
      creatinine based rate calculations. To our knowledge it remains to be determined
      whether the cystatin C estimated glomerular filtration rate can ultimately
      improve the clinical outcome in this population.

PMID- 24679870
TI  - Effect of antioxidants on outcome of testicular torsion in rats of different
      ages.
AB  - PURPOSE: We assessed reproductive and testicular function in adult rats after
      testicular torsion created before, during and after puberty, and with vs without
      resveratrol or arginine treatment. MATERIALS AND METHODS: Age matched rats were
      divided into groups, including simulated surgery without testicular torsion, 720
      degree testicular torsion for 4 hours, testicular torsion with resveratrol
      treatment and testicular torsion with arginine treatment. To study reproductive
      function at age 12 weeks each rat mated with 3 females. The males were sacrificed
      at age 14 weeks. Spermatozoids were collected from the epididymal tail and
      evaluated for concentration, motility and viability. Testicular samples were
      collected for morphological analysis. RESULTS: Reproductive function was not
      altered by testicular torsion but antioxidants improved potency. Compared to sham
      operated and contralateral samples all spermatozoid parameters from testicular
      torsion samples were inferior. Resveratrol and arginine did not improve
      spermatozoid quality or quantity in torsed testes but contralateral samples were
      improved by each drug. The seminiferous epithelium of rats submitted to
      testicular torsion during puberty was least affected. Each antioxidant partially
      to totally prevented the morphological alterations found in rats with untreated
      testicular torsion. Rats submitted to testicular torsion before puberty that were
      treated with antioxidants showed the fewest changes. CONCLUSIONS: Testicular
      morphology was altered less in rats when torsion occurred earlier in life, that
      is during puberty. Treatment with antioxidants improved contralateral
      spermatozoid production and some fertility parameters. Each antioxidant also
      prevented testicular morphology alterations after testicular torsion. Prepubertal
      rats benefited most from antioxidant treatment.

PMID- 24679871
TI  - Why does adenotonsillectomy not correct enuresis in all children with sleep
      disordered breathing?
AB  - PURPOSE: We analyzed the outcome of nocturnal enuresis after adenotonsillectomy
      in children with sleep disordered breathing. We also evaluated differences in
      demographic, clinical, laboratory and polysomnography parameters between
      responders and nonresponders after adenotonsillectomy. MATERIALS AND METHODS: We
      prospectively evaluated children 5 to 18 years old diagnosed with sleep
      disordered breathing (snoring or obstructive sleep apnea syndrome) on
      polysomnography and monosymptomatic primary nocturnal enuresis requiring
      adenotonsillectomy to release upper airway obstruction. Plasma antidiuretic
      hormone and brain natriuretic peptide were measured preoperatively and 1 month
      postoperatively. RESULTS: Sleep studies were done in 46 children and 32 also
      underwent blood testing preoperatively and postoperatively. Mean +/- SD patient
      age was 8.79 +/- 2.41 years and the mean number of wet nights weekly was 6.39 +/-
      1.26. Polysomnography revealed obstructive sleep apnea syndrome in 71.7% of
      patients and snoring in 28.3%. After adenotonsillectomy 43.5% of patients became
      dry. Preoperative polysomnography findings indicated that responders, who were
      dry, had significantly more arousals and obstructive apnea episodes but fewer
      awakenings than nonresponders, who were wet. Significant increases in plasma
      antidiuretic hormone and significant decreases in plasma brain natriuretic
      peptide were seen in all children with no difference between responders and
      nonresponders. No difference between the groups was noted in age, gender, race,
      body mass index, constipation, preoperative number of wet nights weekly or type
      of sleep disordered breathing. CONCLUSIONS: Nocturnal enuresis resolved after
      adenotonsillectomy in almost half of the children with sleep disordered
      breathing. Those who became dry had more frequent arousal episodes caused by
      apnea events than those who remained wet.

PMID- 24679872
TI  - Combined cystometrography and electromyography of the external urethral sphincter
      following complete primary repair of bladder exstrophy.
AB  - PURPOSE: Concern in patients with bladder exstrophy after reconstruction
      regarding potential injury to pelvic neurourological anatomy and a resultant
      functional deficit prompted combined (simultaneous) cystometrography and
      electromyography after complete primary repair of bladder exstrophy. We
      determined whether complete primary repair of bladder exstrophy would adversely
      affect the innervation controlling bladder and external urethral sphincter
      function. MATERIALS AND METHODS: Complete primary repair of bladder exstrophy was
      performed via a modified Mitchell technique in newborns without osteotomy.
      Postoperative evaluation included combined cystometrography and needle electrode
      electromyography via the perineum, approximating the external urethral sphincter
      muscle complex. Electromyography was done to evaluate the external urethral
      sphincter response to sacral reflex stimulation and during voiding. RESULTS: Nine
      boys and 4 girls underwent combined cystometrography/electromyography after
      complete primary repair of bladder exstrophy. Age at study and time after
      complete primary repair of bladder exstrophy was 3 months to 10 years (median
      11.5 months). Cystometrography revealed absent detrusor overactivity and the
      presence of a sustained detrusor voiding contraction in all cases.
      Electromyography showed universally normal individual motor unit action
      potentials of biphasic pattern, amplitude and duration. The external urethral
      sphincter sacral reflex response was intact with a normal caliber with respect to
      Valsalva, Crede, bulbocavernosus and anocutaneous (bilateral) stimulation.
      Synergy was documented by abrupt silencing of external urethral sphincter
      electromyography activity during voiding. CONCLUSIONS: After complete primary
      repair of bladder exstrophy combined cystometrography/electromyography in
      patients with bladder exstrophy showed normal neurourological findings, including
      sacral reflex responses, sustained detrusor voiding contraction and synergic
      voiding, in all patients postoperatively. These findings confirm the safety of
      complete primary repair of bladder exstrophy. Based on our results we have
      discontinued routine electromyography in these patients.

PMID- 24679873
TI  - F2-isoprostanes as a biomarker of oxidative stress in the mouse bladder.
AB  - PURPOSE: We theorized that progressive bladder dysfunction due to clinical
      diagnoses such as outlet obstruction occurs as a result of cyclical oxidative
      stress events. We hypothesized that measurement of F2-isoprostane, a marker of
      lipid peroxidation, could serve as a biomarker of oxidative stress in the murine
      bladder. MATERIALS AND METHODS: At age 5 to 6 weeks oophorectomized female mice
      were subjected to 1 of 2 bladder injury models, that is partial bladder outlet
      obstruction or acute bladder distension. The time points studied after injury
      included 4, 8 and 16 weeks after obstruction, and 0 to 48 hours after acute
      bladder distension. In a separate group short-term repetitive acute bladder
      distension was performed every other day for 14 days. Bladder samples were
      analyzed for F2-isoprostane using gas chromatography and mass spectroscopy. Mean
      tissue F2-isoprostane levels were compared. RESULTS: F2-isoprostane increased
      significantly after 4 weeks of partial bladder outlet obstruction from 1.46 ng/gm
      in controls to 2.31 ng/gm at 4 weeks (p = 0.01). Eight and 16 weeks after partial
      bladder outlet obstruction F2-isoprostane remained significantly elevated (2.39
      and 2.48 ng/gm, respectively). Acute bladder distension resulted in a significant
      increase in F2-isoprostane immediately after distension compared to controls (1.6
      vs 0.75 ng/gm, p = 0.04). In mice that underwent repetitive acute bladder
      distension F2-isoprostane did not change. CONCLUSIONS: Measurement of tissue F2
      isoprostane in the bladder reflects the progression of oxidative stress,
      primarily in chronic injury models such as partial bladder outlet obstruction.
      The usefulness of F2-isoprostane measurements in shorter term injury models
      requires further study.

PMID- 24679874
TI  - Risk stratification of pubertal children and postpubertal adolescents with
      clinical stage I testicular nonseminomatous germ cell tumors.
AB  - PURPOSE: The COG (Children's Oncology Group) currently recommends surveillance
      for all children and adolescents with clinical stage I testicular germ cell
      tumors. However, up to 30% of adults with clinical stage I testicular germ cell
      tumors harbor occult metastatic disease. In adults with clinical stage I
      nonseminoma some groups advocate a risk stratified approach. Occult metastases
      were noted in 50% of patients with features such as lymphovascular invasion or
      embryonal carcinoma predominance in the orchiectomy. However, to our knowledge
      there are no data on the impact of high risk features in such pubertal children
      and postpubertal adolescents. MATERIALS AND METHODS: We reviewed an institutional
      testis cancer database for pubertal children and postpubertal adolescents younger
      than 21 years. We tested the hypothesis that lymphovascular invasion, or 40% or
      greater embryonal carcinoma in the orchiectomy specimen, would increase the risk
      of occult metastases, ie relapse during surveillance or positive nodes on
      retroperitoneal lymph node dissection. RESULTS: We identified 23 patients with a
      median age of 18.6 years (range 7.1 to 20.9) at diagnosis. Of these patients 14
      (60.9%) were on surveillance, 9 (39.1%) underwent primary retroperitoneal lymph
      node dissection and none received initial chemotherapy. Seven patients (30.4%)
      had occult metastatic disease. High risk pathological features were found in the
      orchiectomy specimen in 12 patients (52.2%), including all 12 (52.2%) with 40% or
      greater embryonal carcinoma and 3 (13.0%) with lymphovascular invasion. Seven
      patients (58.3%) with high risk features had occult metastatic disease vs none
      (0%) without high risk features (log rank p = 0.031). CONCLUSIONS: Approximately
      half of pubertal children and postpubertal adolescents with high risk clinical
      stage I testicular germ cell tumors harbor occult metastatic disease. These
      results may be useful when discussing prognosis and treatment with patients and
      families.

PMID- 24679875
TI  - The prevalence of bell clapper anomaly in the solitary testis in cases of prior
      perinatal torsion.
AB  - PURPOSE: Bell clapper anomaly is associated with an increased risk of
      intravaginal testicular torsion. However, perinatal torsion is thought to be
      secondary to an extravaginal process. We quantified the contralateral prevalence
      of bell clapper anomaly in children found to have atrophic testicular nubbins
      secondary to presumed torsion during gestation to better define the subsequent
      risk of metachronous testicular torsion. MATERIALS AND METHODS: Inspection
      results for the presence of contralateral bell clapper anomaly was recorded by a
      single surgeon in 50 consecutive cases in which exploration for nonpalpable
      testes revealed a testicular nubbin. For comparison data were collected in 27
      consecutive cases of acute testicular torsion. Anatomy of the normal
      contralateral testis was compared between the 2 groups. RESULTS: Average age at
      surgery in the perinatal torsion group was 15 months vs 12.7 years in the acute
      torsion group. One case of partial contralateral bell clapper anomaly was
      discovered in the perinatal torsion group but no complete anomaly was found. In
      contrast, in older boys with acute testicular torsion complete bell clapper
      anomaly was found in 21 of the 27 contralateral testes (78%). CONCLUSIONS: In
      older boys with acute testicular torsion contralateral bell clapper anomaly is
      highly prevalent, supporting the standard practice of contralateral testicular
      fixation in this clinical situation. However, the prevalence of contralateral
      bell clapper anomaly is exceedingly small in cases of monorchism after perinatal
      torsion, substantiating an insufficient risk of subsequent torsion to justify
      routine fixation of the solitary testis.

PMID- 24679876
TI  - Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in
      spermatogonial stem cells of cryptorchid testes.
AB  - PURPOSE: Gonocytes differentiate into spermatogonial stem cells, which make it
      possible to maintain spermatogenesis continuously throughout life. We previously
      reported attenuated spermatogonial stem cell activity in cryptorchid testes,
      which resulted in altered spermatogenesis and affected fertility. However, few
      groups have examined the differentiation process from gonocytes to spermatogonial
      stem cells. To clarify the underlying mechanisms comprehensively we performed
      microarray analysis to assess differential expression of transcripts between
      normal and undescended testes in juvenile rats. MATERIALS AND METHODS: Using
      microarray analysis we compared whole mRNA expression of normal and cryptorchid
      testes in a rat model. We subsequently validated differential expression of
      candidate genes by real-time reverse transcriptase-polymerase chain reaction and
      performed immunohistochemistry. We also investigated the methylation status of
      histone H3K4 in cryptorchid testes and the GC-1 spermatogonial cell line.
      RESULTS: We detected 24 up-regulated and 39 down-regulated genes. Of these genes
      Kdm5a expression was significantly higher in undescended testes.
      Immunohistochemistry showed that Kdm5a was localized in the nuclei of gonocytes,
      spermatogonia and spermatocytes. H3K4me2/me3 expression levels were decreased in
      undescended testes at 9 days postpartum. Furthermore, Kdm5a over expression in GC
      1 cells led to increased expression of Esr2, Neurog3, Pou5f1, Ret and Thy1.
      CONCLUSIONS: Recent investigations revealed that not only genetic but also
      epigenetic regulation has a role in spermatogenesis. Kdm5a is likely involved in
      the transformation of gonocytes into spermatogonial stem cells by transcriptional
      regulation of specific genes via H3K4 histone modification. To our knowledge this
      is the first report of epigenetic analysis of germ cell differentiation during
      early spermatogenesis.

PMID- 24679877
TI  - Safety and efficacy of testosterone replacement therapy in adolescents with
      Klinefelter syndrome.
AB  - PURPOSE: We investigated the safety and tolerability of testosterone replacement
      therapy in adolescents with Klinefelter syndrome. MATERIALS AND METHODS: We
      reviewed the medical records of all consecutive adolescents with Klinefelter
      syndrome evaluated between 2007 and 2012. Patients receiving testosterone
      replacement and aromatase inhibitor therapy were identified. Data on
      demographics, physical characteristics, medical history and serum hormone
      concentrations were collected for each patient. We evaluated longitudinal changes
      in serum testosterone, luteinizing hormone and follicle-stimulating hormone as
      well as changes in body mass index after the initiation of testosterone
      replacement therapy. RESULTS: We identified 151 adolescents with Klinefelter
      syndrome. Mean age at presentation was 11.6 years. Testosterone replacement
      therapy and aromatase inhibitors were initiated in 110 and 75 patients,
      respectively, at an average age of 13 to 14 years. Topical testosterone
      replacement therapy was used in 95% of patients with good clinical efficacy and
      compliance based on serial serum testosterone values. After the initiation of
      testosterone replacement therapy average serum testosterone improved from 240 to
      650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased
      with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml,
      respectively. No adverse outcomes related to testosterone replacement therapy
      were reported. CONCLUSIONS: Hormone supplementation with testosterone and
      aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe
      and effective for maintaining serum testosterone within the normal range.
      Compliance with topical formulations is high. Topical testosterone replacement
      therapy is not associated with the suppression of endogenous serum luteinizing
      hormone or follicle-stimulating hormone.

PMID- 24679878
TI  - DNA copy number variations in patients with persistent cloaca.
AB  - PURPOSE: Persistent cloaca is a devastating female anomaly associated with renal
      insufficiency/failure, urinary and fecal incontinence and mullerian dysfunction.
      Genetically engineered murine models of persistent cloaca suggest that this
      anomaly could have a genetic component in humans. Genomic copy number variations
      account for previously unexplained genetic diseases by identifying candidate
      genes in various disorders. We assessed whether novel copy number variations are
      present in patients with persistent cloaca. MATERIALS AND METHODS: With
      institutional review board approval we performed a retrospective chart review to
      identify patients with persistent cloaca. Lymphocyte DNA was prospectively tested
      by whole genome array comparative genomic hybridization. HHAT was Sanger
      sequenced from genomic DNA. RESULTS: At study recruitment mean age was 12 years
      (range 0.5 to 23) in 17 females with cloaca. Seven females (41%) had a solitary
      functioning kidney and 2 each had renal insufficiency and renal replacement
      therapy. The common cloaca channel was 1.5 to 6 cm long in 6 newborns. Six
      patients (35%) had vaginal duplication and 4 had spinal anomalies. Array
      comparative genomic hybridization revealed copy number variations in 7 patients
      (41%), including 5 gains and 2 losses. Two copy number variations were novel,
      including a paternally inherited duplication on 16p13.2 and a de novo deletion on
      1q32.1q32.3. Subsequent sequencing of the candidate gene HHAT identified no
      causal mutations. CONCLUSIONS: Persistent cloaca is a rare but morbid birth
      defect. Copy number variations are common in these females but HHAT mutations are
      not common. Further investigation of these genomic rearrangements may lead to the
      identification of genetic causes of persistent cloaca.

PMID- 24679879
TI  - Long-term efficacy and durability of botulinum-A toxin for refractory
      dysfunctional voiding in children.
AB  - PURPOSE: We evaluated our long-term experience with intrasphincteric botulinum
      toxin A injection in children with dysfunctional voiding. MATERIALS AND METHODS:
      From January 2006 through July 2012 we saw 2,172 neurologically normal children
      due to dysfunctional voiding. Of patients who presented to these visits we
      retrospectively identified the charts of 12 with dysfunctional voiding (8
      females) in whom urotherapy and medical management failed and who underwent
      botulinum toxin A injection to the external urinary sphincter. Mean patient age
      at surgery was 10.5 years (range 4 to 19). Average followup was 45 months (range
      20 to 71). Preoperatively and postoperatively all children were evaluated with
      history and physical examination, voiding diary, renal and pelvic ultrasound with
      post-void residual volume measurement and uroflowmetry. RESULTS: Eight of the 12
      children (67%) experienced significant improvement in voiding parameters. Before
      vs after treatment mean +/- SD post-void residual urine volume was 115 +/- 83 vs
      57 +/- 61 ml (p = 0.016) and the mean maximum flow rate was 11.8 +/- 8.1 vs 20.4
      +/- 7.9 ml per second. Half of the cohort required a second injection an average
      of 15 months later. Three of the 4 patients who failed to show improvement had
      neuropsychiatric problems and 1 had evidence of bladder underactivity.
      CONCLUSIONS: Our results demonstrate reasonable efficacy and durability of
      intrasphincteric botulinum toxin A injection in children with refractory
      dysfunctional voiding. Neuropsychiatric issues appear to negatively influence the
      success rate. Long-term followup is vital to identify patients in whom repeat
      injection may be necessary.

PMID- 24679880
TI  - Dissolution therapy versus shock wave lithotripsy for radiolucent renal stones in
      children: a prospective study.
AB  - PURPOSE: We prospectively evaluated the efficacy of dissolution therapy and
      standard shock wave lithotripsy as a noninvasive modality for radiolucent renal
      stones in children. MATERIALS AND METHODS: A total of 87 children with
      radiolucent renal calculi were included in study. Median age was 2.5 years (range
      0.5 to 13). Computerized tomography was done to confirm a stone density of less
      than 500 HU. Median stone length was 12 mm (range 7 to 24). Patients were
      randomly divided into 2 groups. The medical group of 48 patients received
      potassium sodium hydrogen citrate at a dose of 1 mEq/kg per day for 1 to 3
      months. The shock wave lithotripsy group of 39 patients were treated with a
      Lithotripter S (Dornier Medtech, Kennesaw, Georgia) while under general
      anesthesia. Complications in each group were recorded. Patients were considered
      stone free when imaging within 3 months showed no evidence of stones. RESULTS:
      The stone-free rate was 72.9% for dissolution therapy vs 82.1% after a single
      session of shock wave lithotripsy (p = 0.314). One patient per group experienced
      a pyelonephritis episode during followup (p = 0.698). Three of the 13 patients in
      whom medical regimens failed were noncompliant and 5 ingested the medication
      sporadically. CONCLUSIONS: Medical dissolution therapy is a well tolerated,
      effective treatment for radiolucent renal stones in children. It eliminates the
      need for shock wave lithotripsy in up to 73% of cases.

PMID- 24679881
TI  - Editorial comment.

PMID- 24679882
TI  - Retrograde intrarenal surgery monotherapy versus shock wave lithotripsy for
      stones 10 to 20 mm in preschool children: a prospective, randomized study.
AB  - PURPOSE: We compared the outcome of retrograde intrarenal surgery monotherapy vs
      shock wave lithotripsy for stones 10 to 20 mm in preschool children. MATERIALS
      AND METHODS: This prospective study included 60 children with a mean +/- SD age
      of 2.4 +/- 1.3 years. Patients were randomly divided into 2 groups. Group 1
      underwent shock wave lithotripsy and group 2 underwent retrograde intrarenal
      surgery as monotherapy. Retrograde intrarenal surgery was started using a 7.5Fr
      semirigid ureteroscope (Storz(r)) and the holmium laser, and completed by the
      Flex XTM2 flexible ureterorenoscope. A ureteral access sheath was not used and
      only hydrodilatation was performed. Patients were evaluated preoperatively by
      ultrasound and plain abdominopelvic x-ray. Followup was 3 months. RESULTS: The
      stone-free rate after a single session treatment was 70% and 86.6% in groups 1
      and 2, respectively. Mean operative time was 27.9 +/- 3.5 and 40 +/- 7.8 minutes,
      mean fluoroscopy exposure time was 60 +/- 42 and 50 +/- 35 seconds, and mean
      hospital stay was 6 +/- 2 and 12 +/- 8 hours, respectively. No major complication
      occurred in either group and no child in either group received blood transfusion.
      Nine group 1 patients needed a second shock wave lithotripsy session, of whom 2
      required a third session. At 3 months the overall stone-free rate was 93.3% and
      96.6% in groups 1 and 2, respectively. CONCLUSIONS: Retrograde intrarenal surgery
      is an option for treating medium sized renal stones in preschool children with
      results comparable to those of shock wave lithotripsy and a safe short-term
      outcome.

PMID- 24679883
TI  - Sigmoid vaginoplasty with a modified single Monti tube: a pediatric case series.
AB  - PURPOSE: No consensus exists regarding the most effective procedure for neovagina
      formation. We describe our experience with modified single Monti tube
      colovaginoplasty in pediatric patients with disorders of sexual differentiation.
      MATERIALS AND METHODS: Six patients were retrospectively identified who underwent
      primary sigmoid vaginoplasty with a modified single Monti tube between 2009 and
      2012. Data were collected from patient charts. The procedure is performed by
      isolating an 8 to 10 cm segment of distal sigmoid colon or proximal rectum, which
      is detubularized along the anterior mesentery, folded and retubularized
      longitudinally, leaving the mesentery in a cephalad position. A channel is
      dissected in the pelvis to accommodate the neovagina. RESULTS: Mean patient age
      was 12.7 years (range 6 to 17). The primary diagnosis was androgen insensitivity
      in 3 cases (50%), and Mayer-Rokitansky syndrome, partial androgen insensitivity
      and persistent cloaca in 1 each (16.7%). Chromosomal analysis revealed 46XY in 4
      patients (66.7%). Median followup was 7.9 months (range 3 to 41). One patient who
      engages in vaginal intercourse reported satisfactory vaginal length without
      discomfort. In 1 patient an anastomotic stricture developed, which was managed by
      buccal mucosal grafting. CONCLUSIONS: Modified single Monti tube sigmoid
      vaginoplasty is a safe, effective technique for neovagina formation in pediatric
      patients with disorders of sexual differentiation. Compared to other existing
      methods, our technique allows for the use of shorter bowel segments with
      decreased tension of the vascular pedicle.

PMID- 24679885
TI  - Recent trends in the surgical management of primary vesicoureteral reflux in the
      era of dextranomer/hyaluronic acid.
AB  - PURPOSE: Since its inception as a technology in the United States, endoscopic
      correction of vesicoureteral reflux has become a popular treatment option in
      children with vesicoureteral reflux with reported wide use. We determined whether
      the increasing trend in use in the United States after the introduction of
      dextranomer/hyaluronic acid has been sustained. MATERIALS AND METHODS: We
      abstracted data on pediatric patients treated with ureteral reimplantation or
      dextranomer/hyaluronic acid intervention for vesicoureteral reflux from 2004 to
      2011 from the PHIS (Pediatric Health Information System) database. Patients with
      coding data indicating diagnoses other than primary vesicoureteral reflux and
      hospitals reporting less than 80% of ambulatory surgery cases by CPT code were
      excluded from study. RESULTS: We identified 14,430 patients (17,826 procedures),
      of whom 49% underwent reimplantation and 51% underwent dextranomer/hyaluronic
      acid injection. Of the patients 83% were female with a median age at surgery of
      4.7 years (IQR 2.5-7.2). Linear regression showed a significant downward trend in
      the average total number of antireflux operations per institution during the
      study period. This was attributable to a decrease in the average rate of
      dextranomer/hyaluronic acid interventions because the average reimplantation rate
      remained stable during this time. CONCLUSIONS: At freestanding pediatric
      hospitals enrolled in the PHIS database there is a trend toward decreasing
      intervention for primary vesicoureteral reflux, which appears to be due to
      decreased use of injection therapy. This may reflect a philosophical change in
      reflux management by injection therapy.

PMID- 24679886
TI  - Most infants with dilating vesicoureteral reflux can be treated nonoperatively.
AB  - PURPOSE: Dilating vesicoureteral reflux provokes concern for physicians and
      parents that often leads to corrective surgery in young children. Since there are
      limited data describing the natural history of dilating vesicoureteral reflux in
      infants, we identified factors predictive of resolution/improvement in infants
      initially treated nonoperatively. MATERIALS AND METHODS: We reviewed the medical
      records of 90 infants 6 months old or younger from 2004 to 2010 who were referred
      for prenatal hydronephrosis or initial febrile urinary tract infection and found
      to have dilating vesicoureteral reflux (grade 3 or greater). Variables of
      interest included presentation, dimercapto-succinic acid results, sex,
      breakthrough febrile urinary tract infections, reflux grade and bilateral reflux.
      Cox regression analysis was performed to determine predictors of spontaneous
      resolution and/or improvement to reflux grade less than 3 as well as predictors
      of surgical intervention. RESULTS: Included in final analysis were 80 infants
      (113 renal units). Of the patients 51 (64%) experienced spontaneous
      resolution/improvement with a mean followup of 29 months before resolution,
      discharge home and/or end of followup. Only 20 patients (25%) underwent surgery.
      Cox regression analysis revealed that a normal initial dimercapto-succinic acid
      scan, initial reflux grade less than 5 and absent breakthrough febrile urinary
      tract infections were predictive of reflux resolution/improvement (p <0.05).
      Dimercapto-succinic acid scan abnormalities, prenatal hydronephrosis and
      breakthrough febrile urinary tract infections were significant predictors of
      surgery (p <0.05). CONCLUSIONS: Dilating vesicoureteral reflux in infancy often
      resolves/improves spontaneously. Therefore, surgery should be directed toward
      patients unlikely to experience resolution, ie those with an abnormal initial
      dimercapto-succinic acid scan, grade 5 vesicoureteral reflux and breakthrough
      febrile urinary tract infections.

PMID- 24679887
TI  - A comparison of inpatient versus outpatient resistance patterns of pediatric
      urinary tract infection.
AB  - PURPOSE: Prior single center studies showed that antibiotic resistance patterns
      differ between outpatients and inpatients. We compared antibiotic resistance
      patterns for urinary tract infection between outpatients and inpatients on a
      national level. MATERIALS AND METHODS: We examined outpatient and inpatient
      urinary isolates from children younger than 18 years using The Surveillance
      Network (Eurofins Scientific, Luxembourg, Luxembourg), a database of antibiotic
      susceptibility results, as well as patient demographic data from 195 American
      hospitals. We determined the prevalence and antibiotic resistance patterns of the
      6 most common uropathogens, including Escherichia coli, Proteus mirabilis,
      Klebsiella, Enterobacter, Pseudomonas aeruginosa and Enterococcus. We compared
      differences in uropathogen prevalence and resistance patterns for outpatient and
      inpatient isolates using chi-square analysis. RESULTS: We identified 25,418
      outpatient (86% female) and 5,560 inpatient (63% female) urinary isolates.
      Escherichia coli was the most common uropathogen overall but its prevalence
      varied by gender and visit setting, that is 79% of uropathogens overall for
      outpatient isolates, including 83% of females and 50% of males, compared to 54%
      for overall inpatient isolates, including 64% of females and 37% of males (p
      <0.001). Uropathogen resistance to many antibiotics was lower in the outpatient
      vs inpatient setting, including trimethoprim/sulfamethoxazole 24% vs 30% and
      cephalothin 16% vs 22% for E. coli (each p <0.001), cephalothin 7% vs 14% for
      Klebsiella (p = 0.03), ceftriaxone 12% vs 24% and ceftazidime 15% vs 33% for
      Enterobacter (each p <0.001), and ampicillin 3% vs 13% and ciprofloxacin 5% vs
      12% for Enterococcus (each p <0.001). CONCLUSIONS: Uropathogen resistance rates
      of several antibiotics are higher for urinary specimens obtained from inpatients
      vs outpatients. Separate outpatient vs inpatient based antibiograms can aid in
      empirical prescribing for pediatric urinary tract infections.

PMID- 24679888
TI  - Mitrofanoff for valve bladder syndrome: effect on urinary tract and renal
      function.
AB  - PURPOSE: Despite early diagnosis and valve ablation, progressive renal impairment
      develops in a significant proportion of boys born with posterior urethral valves.
      Bladder dysfunction is thought to have an important role in the etiology of this
      renal deterioration. We report the outcome of treating bladder dysfunction with
      clean intermittent catheterization and overnight drainage via a Mitrofanoff
      appendicovesicostomy with respect to upper tract imaging, urodynamic findings and
      renal function. MATERIALS AND METHODS: All patients were established on a clean
      intermittent catheterization program via the Mitrofanoff stoma, including 3 or 4
      daytime catheterizations and overnight drainage with an indwelling catheter. We
      analyzed trends in serum creatinine, renal ultrasound appearance and urodynamic
      data. RESULTS: Mitrofanoff formation was performed in 24 patients with valve
      bladder syndrome. Median followup was 6.2 years. Hydronephrosis, quantified by
      combined anteroposterior diameter measurements of the renal pelvis, significantly
      improved with a mean combined anteroposterior diameter reduction of 14.2 mm (95%
      CI 7.6-20.9, p <= 0.001). Overall bladder dysfunction improved. Capacity was
      decreased in 9 of 12 patients (75%) initially compared with 12 of 21 (57%) after
      Mitrofanoff surgery (p = 0.457). Compliance was poor in 75% of patients initially
      vs 28.6% at followup (p = 0.014). Despite improvements in hydronephrosis and
      urodynamic parameters the mean estimated glomerular filtration rate deteriorated.
      End stage renal failure developed in 35% of cases during followup. CONCLUSIONS:
      Treatment of valve bladder with clean intermittent catheterization and overnight
      drainage via a Mitrofanoff stoma can achieve significant improvements in
      hydronephrosis and bladder dysfunction urodynamic parameters. However, it does
      not prevent renal deterioration.

PMID- 24679889
TI  - Health related quality of life in patients with bladder exstrophy: a call for
      targeted interventions.
AB  - PURPOSE: Research on health related quality of life in patients with bladder
      exstrophy has demonstrated mixed results compared to population samples. Few
      studies have had a comparison group with a urological disorder and none
      correlated body image to health related quality of life. We compared health
      related quality of life in patients with bladder exstrophy to that in patients
      with kidney stones and correlated body image to health related quality of life in
      the bladder exstrophy population. MATERIALS AND METHODS: Participants included 24
      patients with kidney stones and 24 with bladder exstrophy. Patient age was 8 to
      25 years. Participants completed the PedsQL (Pediatric Quality of Life Inventory)
      and the 25-item multiple choice UBIQ (Urological Body Image Questionnaire), which
      was created for the current study. RESULTS: Compared to patients with kidney
      stones those with bladder exstrophy indicated significantly higher scores on
      physical functioning (p = 0.0005) and overall health related quality of life (p =
      0.02) in the 8 to 17-year-old cohort. When health related quality of life was
      compared to body image in patients with bladder exstrophy, lower social scores
      were associated with those who worried about friends finding out about the
      condition (p = 0.01) and about having romantic relationships (p = 0.003). Lower
      social (p = 0.006) and emotional (p = 0.009) functioning scores were associated
      with patients who thought that they were less likely to have romantic
      relationships. CONCLUSIONS: The finding that patients with bladder exstrophy had
      a better physical functioning score than those with kidney stones is not
      surprising, given the morbidity of active stone disease. The negative
      correlations with body image in the bladder exstrophy population may be due to
      the possibility of others discovering the condition and the perceived likelihood
      of not having romantic relationships.

PMID- 24679890
TI  - EMAS position statement: The management of postmenopausal women with vertebral
      osteoporotic fracture.
AB  - INTRODUCTION: Osteoporotic vertebral fractures are associated with significant
      morbidity, excess mortality as well as health and social service expenditure.
      Additionally, women with a prevalent osteoporotic vertebral fracture have a high
      risk of experiencing a further one within one year. It is therefore important for
      the physician to use a diagnostic and therapeutic algorithm for early detection
      and effective treatment of vertebral fractures. AIMS: The aim of this position
      statement is to provide and critically appraise evidence on the management of
      women with a vertebral osteoporotic fracture. MATERIALS AND METHODS: Literature
      review and consensus of expert opinion. RESULTS AND CONCLUSIONS: The management
      of women with osteoporotic vertebral fractures includes measures to reduce pain
      providing early mobility, to support the affected spine ensuring fracture
      healing, as well as starting treatment for osteoporosis itself. Any other
      underlying pathology should be sought and treated. Early detection and treatment
      is essential as there is an increased risk of further fractures in patients with
      vertebral fractures. Treatment will depend on the underlying causes of bone loss,
      efficacy in any particular situation, cost and patient preference.

PMID- 24679891
TI  - Ospemifene, a non-oestrogen selective oestrogen receptor modulator for the
      treatment of vaginal dryness associated with postmenopausal vulvar and vaginal
      atrophy: a randomised, placebo-controlled, phase III trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of ospemifene, a novel selective
      oestrogen receptor modulator, in the treatment of vaginal dryness in
      postmenopausal women with vulvovaginal atrophy (VVA). STUDY DESIGN: A 12 week,
      multicentre, randomised, double-blind, parallel-group phase III study of women
      (40-80 years) with VVA and self-reported vaginal dryness as their most bothersome
      symptom. MAIN OUTCOME MEASURES: The co-primary efficacy endpoints were the change
      from baseline to Week 12 in (1) percentage of parabasal cells in the maturation
      index (MI), (2) percentage of superficial cells in the MI, (3) vaginal pH, and
      (4) severity of vaginal dryness. Safety assessments included physical
      examination, cervical Papanicolaou test and clinical laboratory analyses.
      Endometrial thickness and histology was also assessed. RESULTS: A total of 314
      women were randomised to once-daily ospemifene 60 mg/day (n=160) or placebo
      (n=154). Significant improvements in the percentages of parabasal and superficial
      cells in the MI and vaginal pH were observed with ospemifene compared with
      placebo (p<0.001 for all parameters). The mean change from baseline in severity
      score of vaginal dryness reported by women receiving ospemifene compared with
      those receiving placebo approached statistical significance (p=0.080).
      Improvements in each of the four co-primary endpoints with ospemifene were
      statistically significant compared to placebo in the per protocol population. The
      majority of treatment-emergent adverse events were considered mild to moderate in
      severity. CONCLUSIONS: Once-daily oral ospemifene 60 mg was effective for the
      treatment of VVA in postmenopausal women with vaginal dryness.

PMID- 24679892
TI  - Management of infertility in women over 40.
AB  - Women's fertility potential is declining with age because of multiples intrinsic
      and extrinsic factors such as life style, oxidative stress and/or endocrine
      disruptors and is affecting the ability of these women to conceive naturally.
      This declining fertility potential and the late age of motherhood is increasing
      significantly the number of patients consulting infertility specialists.
      Different strategies of investigation and management are proposed to patients
      over 40 in order to overcome their infertility and improve the live birth rate in
      these patients. Intra Uterine Insemination (IUI) in women over 40 is associated
      with a low rate of ongoing pregnancy and IUI should not therefore be offered
      always as the first line of treatment. When the predictive factors are positive
      IVF/ICSI seem to be good alternatives until 43 years of age. Customized ovarian
      stimulation and flexible laboratory methods such as in vitro maturation (IVM),
      preimplantation genetic diagnosis (PGD), embryo vitrification and transfer after
      thawing in subsequent natural or artificial cycles can improve the success rate
      of ART in patients over 40. Meanwhile, oocyte and embryos donation remain good
      options for patient over 40 with a bad prognosis and can lead to successful
      ongoing pregnancies until 45 years of age. Ovarian tissue cryopreservation,
      oocyte vitrification at the germinal vesicle (GV) stage or metaphase II stage
      present a breakthrough for fertility preservation but the ideal age for starting
      fertility preservation is still debated as well as the minimum number of oocytes
      to be vitrified in order to optimize the chances of pregnancy when needed at an
      older age. This manuscript reports the results of our own experience from
      patients older than 40 in the light of the published data and discusses the
      different therapeutic alternatives which can be proposed to patients over 40
      consulting ART centres.

PMID- 24679893
TI  - EEG/fMRI contributions to our understanding of genetic generalized epilepsies.
AB  - The first reports of combined EEG and fMRI used for evaluation of epileptic
      spikes date back to the mid-90s. At that time, the technique was called EEG
      triggered fMRI--the "triggered" corresponded to an epilepsy specialist reviewing
      live EEG while the patient was located in the scanner; after the spike was
      identified, a scan was initiated to collect the data. Since then major progress
      has been made in combined EEG/fMRI data collection and analyses. These advances
      allow studying the electrophysiology of genetic generalized epilepsies (GGEs) in
      vivo in greater detail than ever. In addition to continuous data collection, we
      now have better methods for removing physiologic and fMRI-related artifacts, more
      advanced understanding of the hemodynamic response functions, and better
      computational methods to address the questions regarding the origins of the
      epileptiform discharge generators in patients with GGEs. These advances have
      allowed us to examine numerous cohorts of children and adults with GGEs while not
      only looking for spike and wave generators but also examining specific types of
      GGEs (e.g., juvenile myoclonic epilepsy or childhood absence epilepsy), drug
      naive patients, effects of medication resistance, or effects of epileptiform
      abnormalities and/or seizures on brain connectivity. While the discussion is
      ongoing, the prevailing thought is that the GGEs as a group are a network
      disorder with participation from multiple nodes including the thalami and cortex
      with the clinical presentation depending on which node of the participating
      network is affected by the disease process. This review discusses the
      contributions of EEG/fMRI to our understanding of GGEs.

PMID- 24679894
TI  - Dietary patterns and risk of death and progression to ESRD in individuals with
      CKD: a cohort study.
AB  - BACKGROUND: Nutrition is linked strongly with health outcomes in chronic kidney
      disease (CKD). However, few studies have examined relationships between dietary
      patterns and health outcomes in persons with CKD. STUDY DESIGN: Observational
      cohort study. SETTING & PARTICIPANTS: 3,972 participants with CKD (defined as
      estimated glomerular filtration rate < 60 mL/min/1.73 m2 or albumin-creatinine
      ratio >= 30 mg/g at baseline) from the Reasons for Geographic and Racial
      Differences in Stroke (REGARDS) Study, a prospective cohort study of 30,239 black
      and white adults at least 45 years of age. PREDICTORS: 5 empirically derived
      dietary patterns identified by factor analysis: "convenience" (Chinese and
      Mexican foods, pizza, and other mixed dishes), "plant-based" (fruits and
      vegetables), "sweets/fats" (sugary foods), "Southern" (fried foods, organ meats,
      and sweetened beverages), and "alcohol/salads" (alcohol, green-leafy vegetables,
      and salad dressing). OUTCOMES: All-cause mortality and end-stage renal disease
      (ESRD). RESULTS: 816 deaths and 141 ESRD events were observed over approximately
      6 years of follow-up. There were no statistically significant associations of
      convenience, sweets/fats, or alcohol/salads pattern scores with all-cause
      mortality after multivariable adjustment. In Cox regression models adjusted for
      sociodemographic factors, energy intake, comorbid conditions, and baseline kidney
      function, higher plant-based pattern scores (indicating greater consistency with
      the pattern) were associated with lower risk of mortality (HR comparing fourth to
      first quartile, 0.77; 95% CI, 0.61-0.97), whereas higher Southern pattern scores
      were associated with greater risk of mortality (HR comparing fourth to first
      quartile, 1.51; 95% CI, 1.19-1.92). There were no associations of dietary
      patterns with incident ESRD in multivariable-adjusted models. LIMITATIONS:
      Missing dietary pattern data, potential residual confounding from lifestyle
      factors. CONCLUSIONS: A Southern dietary pattern rich in processed and fried
      foods was associated independently with mortality in persons with CKD. In
      contrast, a diet rich in fruits and vegetables appeared to be protective.

PMID- 24679895
TI  - Clinical predictors of individual cognitive fluctuations in patients undergoing
      hemodialysis.
AB  - BACKGROUND: Cognitive impairment in hemodialysis (HD) patients is frequent and
      mediated by several factors. It is unclear which patients are more susceptible to
      cognitive variations around the dialysis cycle and which clinical factors may
      play a mediator role. We aimed to answer these issues by investigating
      intraindividual changes within the dialysis cycle. STUDY DESIGN: Cross-sectional
      observational study with repeated measures. SETTING & PARTICIPANTS: 47 HD
      patients and 40 controls without kidney disease, both without history of
      neurologic disease. PREDICTORS: Dialysis vintage, disease duration, vascular risk
      factors, comorbidity index score, intradialytic weight change, frequency of
      hypotensive episodes, and biochemical levels (hemoglobin, leukocytes, urea,
      creatinine, sodium, and potassium). Covariates included demographics (age,
      education, and sex). OUTCOMES & MEASUREMENTS: Significant individual
      deterioration in attention and executive functions (phasic and intrinsic
      alertness, Stroop test, and Trail Making Test) after dialysis, as measured by a
      regression-based reliable change method. Regression models were used to identify
      clinical predictors of individual cognitive decline after dialysis. RESULTS:
      After dialysis, patients primarily showed prolonged reaction times and
      psychomotor slowing. However, individual-based analyses revealed that
      fluctuations in attention and executive functions were present in only a minority
      of patients. Significant individual fluctuations on particular attention and
      executive tasks were associated moderately with intradialytic hypotensive
      episodes, as well as with psychoactive medication, and were predicted weakly by
      blood leukocyte count, sodium level, dialysis vintage, and volume. LIMITATIONS:
      Small sample size; patient group younger and healthier than the overall HD
      population, limiting generalizability. CONCLUSIONS: Only a minority of patients
      exhibit significant individual cognitive fluctuations, predominantly showing
      deterioration after dialysis in attention and executive functions. Susceptibility
      to such fluctuations was predicted in part by both HD-dependent and -independent
      factors.

PMID- 24679896
TI  - Blood pressure goals: how low is safe in CKD?

PMID- 24679897
TI  - New frontiers in sphingolipid biology. Preface.

PMID- 24679898
TI  - Holmes' and palatal tremor following brainstem haemorrhage.

PMID- 24679900
TI  - Survival in Parkinson's disease. Relation with motor and non-motor features.
AB  - BACKGROUND: Survival in patients with Parkinson's disease is reduced as compared
      to the general population. We aimed to identify motor and non-motor features that
      predict mortality in Parkinson's disease. METHODS: A broad range of motor and non
      motor features were assessed in a hospital-based cohort of 414 patients with
      Parkinson's disease, who underwent five annual follow-up examinations including
      vital status assessment. Multivariable Cox's proportional hazards regression
      analysis was used to evaluate the association between baseline characteristics
      and mortality risk. Stepwise regression with backward elimination was carried out
      to determine the best model to predict mortality in Parkinson's disease. RESULTS:
      After a mean follow-up period of 4.3 years, 49 (11.8%) patients had died. In the
      stepwise regression model, predictors of mortality in Parkinson's disease were
      higher age, male sex, cognitive impairment, higher postural instability gait
      disorder score, and the presence of psychotic symptoms. CONCLUSIONS: Higher age,
      male sex, cognitive impairment, higher postural instability gait disorder score,
      and the presence of psychotic symptoms are independent predictors of decreased
      survival in Parkinson's disease. Mortality in Parkinson's disease thus seems to
      be affected mainly by non-dopaminergic and non-motor features.

PMID- 24679899
TI  - Alzheimer's-related changes in non-demented essential tremor patients vs.
      controls: links between tau and tremor?
AB  - BACKGROUND: In addition to tremor, patients with essential tremor (ET) may
      exhibit non-motor features, including a range of cognitive deficits. Several
      prospective, population-based epidemiological studies have reported an
      association between ET and incident dementia, especially Alzheimer's disease
      (AD). Moreover, in a brain repository-based study, a larger than expected
      proportion of ET patients also developed pathological changes characteristic of
      progressive supranuclear palsy, further suggesting a link between ET and tau
      pathology. METHODS: We selected a group of ET patients that were free of dementia
      clinically and without AD on postmortem examination. Our hypothesis was that
      neuronal tauopathic burden would be higher in the brains of these ET patients
      compared to controls. We compared Braak stage for neuronal tangles and Consortium
      to Establish a Registry for Alzheimer's Disease (CERAD) scores for neuritic
      plaques in the two groups. RESULTS: The two groups were similar in age (82.6 +/-
      6.0 vs. 80.4 +/- 8.1, p = 0.22). The 40 ET patients had a higher Braak
      neurofibrillary stage than 32 controls (means: 2.2 +/- 1.2 vs. 1.2 +/- 1.1;
      medians: 2.0 vs. 1.0, p < 0.001). Meanwhile, CERAD scores for neuritic plaques
      were similar in patients and controls (means: 0.6 +/- 0.9 vs. 0.5 +/- 0.6;
      medians: 0.0 vs. 0.0, p = 0.83). CONCLUSION: While ET itself is not a tauopathy
      (i.e., a neurodegenerative disorder among whose main features are accumulation of
      hyperphosphorylated tau protein), ET may predispose individuals to accumulate
      more widespread cellular tau aggregates, and thus tau could play a central role
      in the cognitive impairment that can accompany ET.

PMID- 24679901
TI  - Early phenotypic differences between Parkinson's disease patients with and
      without freezing of gait.
AB  - BACKGROUND: Previous studies have associated freezing of gait in Parkinson's
      disease with the presence of specific phenotypic features such as mood
      disturbances, REM sleep behavior disorder and selective cognitive impairments.
      However, it is not clear whether these features are present in the earlier stages
      of disease or simply represent a more general pattern of progression. To
      investigate this issue, the current study evaluated motor, cognitive, affective
      and autonomic features as well as REM sleep behavior disorder in Parkinson's
      disease patients in the early stages of the condition. METHODS: Thirty-eight
      freezers and fifty-three non-freezers with disease duration of less than five
      years and a Hoehn and Yahr stage of less than three were included in this study.
      The groups were matched on a number of key disease features including age,
      disease duration, motor severity and dopamine dose equivalence. Furthermore,
      patients were assessed on measures of motor, cognitive, affective and autonomic
      features, as well as REM sleep behavior disorder. RESULTS: Compared to non
      freezers, patients with freezing of gait had significantly more non-tremor
      symptoms and a selective impairment on executive functions, such as set-shifting
      ability and working memory. Freezers and non-freezers did not differ on measures
      of tremor, autonomic function, REM sleep behavior disorder, mood or more general
      cognition. CONCLUSION: These results suggest the pathophysiological mechanisms
      underlying freezing of gait in the early clinical stages of Parkinson's disease
      are likely to be related to specific changes in the frontostriatal pathways
      rather than being due to brainstem or more diffuse neuropathology.

PMID- 24679902
TI  - Oral manifestations in patients with neurofibromatosis type-1: a comprehensive
      literature review.
AB  - Oral health status is jeopardized in patients with neurofibromatosis (NF) type-1
      (NF-1). The aim of the present study was to comprehensively review the oral
      manifestations in NF-1 patients. PubMed/Medline and Google-Scholar databases were
      explored using different keywords. Reviews, commentaries, letters to Editor and
      articles published in languages other than English were excluded. RESULTS:
      Neurofibromas of oral and perioral soft tissues with subsequent periodontitis,
      impacted and supernumerary teeth, enlarged alveolar process with dental spacing,
      morphological changes in teeth and class III molar relationship have been
      reported in NF-1 patients. Plexiform neurofibromas were reported both in oral
      soft tissue, maxilla and mandible with evidence of malignant transformation in
      some cases. Facial skeletal abnormalities, including enlargement of mandibular
      foramen, increased dimensions of the coronoid and sigmoid notches and notching of
      the posterior border of the mandible have also been reported. Association between
      dental caries and NF-1 remains unclear.

PMID- 24679903
TI  - Smart and green interfaces: from single bubbles/drops to industrial environmental
      and biomedical applications.
AB  - Interfaces can be called Smart and Green (S&G) when tailored such that the
      required technologies can be implemented with high efficiency, adaptability and
      selectivity. At the same time they also have to be eco-friendly, i.e. products
      must be biodegradable, reusable or simply more durable. Bubble and drop
      interfaces are in many of these smart technologies the fundamental entities and
      help develop smart products of the everyday life. Significant improvements of
      these processes and products can be achieved by implementing and manipulating
      specific properties of these interfaces in a simple and smart way, in order to
      accomplish specific tasks. The severe environmental issues require in addition
      attributing eco-friendly features to these interfaces, by incorporating
      innovative, or, sometimes, recycle materials and conceiving new production
      processes which minimize the use of natural resources and energy. Such concept
      can be extended to include important societal challenges related to support a
      sustainable development and a healthy population. The achievement of such
      ambitious targets requires the technology research to be supported by a robust
      development of theoretical and experimental tools, needed to understand in more
      details the behavior of complex interfaces. A wide but not exhaustive review of
      recent work concerned with green and smart interfaces is presented, addressing
      different scientific and technological fields. The presented approaches reveal a
      huge potential in relation to various technological fields, such as
      nanotechnologies, biotechnologies, medical diagnostics, and new or improved
      materials. 

PMID- 24679904
TI  - Descriptive study of sensitization to methylchloroisothiazolinone and
      methylisothiazolinone in a skin allergy unit.
AB  - BACKGROUND: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) are
      heterocyclic compounds used as preservatives in cosmetic and industrial products.
      They continue to be common allergens, causing positive patch test reactions in 2%
      to 4% of patients tested. MATERIAL AND METHODS: We searched the database at our
      skin allergy unit for all cases of sensitization to MCI/MI and MI diagnosed
      between January 1980 and March 2013. RESULTS: Patch tests were performed with
      MCI/MI in 8705 patients and with MI in 404 patients. In total, 222 patients
      (2.55%) were sensitized to MCI/MI and 21 (5.19%) were sensitized to MI. The
      incidence of MCI/MI cases peaked between 1998 and 2005 and again between 2009 and
      2013. Of the 222 patients with MCI/MI sensitization, 142 were women (64%) and 49
      were men (36%); the mean age was 43 years. The most frequently affected areas
      were the hands (54% of cases), the arms (36%), and the face (35%); 75.67% of
      cases were due to cosmetics and 2.25% were due to paint. Of the 21 patients with
      MI sensitization (mean age, 50 years), 12 were women (57%) and 9 were men (43%).
      The most common site of involvement in this group was the face (71% of cases),
      followed by the arms (38%) and the hands (29%). All the cases were due to
      cosmetics. CONCLUSIONS: Our data show that sensitization to the combination of
      MCI and MI and MI alone has increased in recent years. It would appear to be
      necessary to add MI to the baseline patch test series, although the test
      concentration has yet to be determined.

PMID- 24679906
TI  - Impact of coronary stent designs on acute stent recoil.
AB  - BACKGROUND: Acute stent recoil has been often observed following stent delivery
      balloon deflation in coronary arteries and the recoil rate varies by stent
      design. Accordingly, the purpose of the present study was to evaluate the impact
      of stent designs on acute stent recoil after new generation drug-eluting stent
      implantation. METHODS AND RESULTS: A total of 154 lesions [56 treated with
      biolimus-eluting stent (BES), 46 with cobalt chromium everolimus-eluting stent
      (CoCr-EES), and 52 with platinum chromium everolimus-eluting stent (PtCr-EES)]
      were evaluated. Quantitative coronary angiography was used to measure the minimal
      lumen diameter (MLD). MLD1 was defined as a MLD of complete expansion of the last
      stent delivery balloon at the highest pressure. MLD2 was defined as a MLD
      immediately after the last stent delivery balloon deflation. Acute stent recoil
      was determined by the calculation as (MLD1-MLD2)/MLD1. Acute stent recoil was
      significantly higher in the CoCr-EES group versus the BES group and PtCr-EES
      group (10.1 +/- 6.9%, 6.7 +/- 5.5%, and 6.5 +/- 4.8%, respectively, p = 0.01).
      Multivariate linear regression analysis demonstrated that the use of CoCr-EES and
      the number of stent delivery balloon inflations were independent predictors of
      acute stent recoil (r = 0.26, beta = 0.21, p = 0.01 and r = -0.51, beta = -0.58,
      p < 0.01, respectively). CONCLUSION: Acute stent recoil occurred more frequently
      with the CoCr-EES compared with both BES and PtCr-EES. Strategies with multiple
      balloon inflation might be needed to overcome this recoil phenomenon.

PMID- 24679905
TI  - 1,5-Anhydro-D-glucitol predicts coronary artery disease prevalence and
      complexity.
AB  - BACKGROUND: The relationship between hemoglobin A1c (HbA1c) levels and coronary
      artery disease (CAD) has previously been confirmed. Serum 1,5-anhydro-D-glucitol
      (1,5-AG) levels are a useful clinical marker for short-term glycemic status that
      reflect glycemic excursions with greater sensitivity compared with HbA1c,
      specifically in the postprandial state. Postprandial hyperglycemia is an
      important CAD risk factor. Thus, the aim of this study was to compare HbA1c with
      1,5-AG as a CAD predictor. METHODS: The subjects consisted of 336 consecutive
      patients who underwent their first coronary angiography between July 2011 and
      March 2013. The relationship between CAD prevalence and HbA1c as well as CAD
      prevalence and 1,5-AG levels was evaluated. The correlation between CAD
      complexity and HbA1c or 1,5-AG was also assessed. CAD complexity was evaluated by
      the SYNTAX score. RESULTS: CAD patients presented with significantly lower 1,5-AG
      and higher HbA1c values than patients without CAD (11.6 MUg/ml [6.1, 19.1] vs.
      17.6 MUg/ml [11.9, 25.0], p<0.001, and 6.0% [5.6, 7.1] vs. 5.7% [5.4, 6.2],
      p<0.001, respectively) (median [25th, 75th percentiles]). According to logistic
      regression analysis, 1,5-AG was a predictor of CAD prevalence (odds ratio 0.94,
      95% confidence interval 0.90-0.97). However, HbA1c levels did not present a
      predictive value for CAD. Levels of 1,5-AG and HbA1c were significantly
      correlated with SYNTAX scores (rho=-0.27, p<0.001; and rho=0.23, p<0.001,
      respectively). CONCLUSIONS: The use of 1,5-AG, may be superior to HbA1c in
      predicting CAD prevalence. Both 1,5-AG and HbA1c correlate with CAD complexity.

PMID- 24679907
TI  - The effect of Arbas Cashmere goat bone marrow stromal cells on production of
      transgenic cloned embryos.
AB  - The aim of this study was to develop a method for the in vitro separation and
      culture of Arbas Cashmere goat bone marrow stromal cells (gBMSCs). Arbas Cashmere
      gBMSCs were isolated and cultured in vitro, and cell surface markers were
      identified immunohistochemically. The gBMSCs were differentiated into neurocytes
      and osteoblasts, and the expression of neuron-specific enolase and osteocalcin
      was identified by immunohistochemistry. The gBMSCs and goat fetal fibroblast
      cells (gFFCs) were compared for transient transfection efficiency and fluorescent
      colony-forming efficiency with Arbas Cashmere gFFCs as a control. pDsRed2-1
      encodes DsRed2, a variant of the Discosoma sp. red fluorescent protein (DsRed).
      In addition, the coding sequence for DsRed2 contains a series of silent base-pair
      changes for higher expression in mammalian cells. Of the gBMSCs-pDsRed2-1, one
      fraction was tested for pluripotency, whereas the other fraction was manipulated
      using somatic cell nuclear transfer, and the in vitro growth status of transgenic
      embryos derived from gBMSCs-pDsRed2-1 and gFFCs-pDsRed2-1 was compared. The
      findings showed that gBMSCs were isolated and amplified to express CD29, CD44,
      and CD90 through adherent culture, with no marked signs of aging after multiple
      passages. Expression of neuron-specific enolase and osteocalcin by gBMSCs and
      gBMSCs-pDsRed2-1 was strongly induced by neuronal and osteogenic differentiation,
      whereas the integrated exogenous genes did not influence pluripotency (P > 0.05).
      The transient transfection efficiencies of gBMSCs and gFFCs after 48 hours were
      not significantly different; however, the fluorescent colony-forming efficiency
      of gBMSCs-pDsRed2-1 after G418 screening was approximately 13% higher than that
      of gFFCs-pDsRed2-1. The convergence and cleavage rates of cloned embryos derived
      from gBMSCs-pDsRed2-1 were higher than those derived from gFFCs-pDsRed2-1,
      whereas their eight-cell and blastocyst rates were similar. The red fluorescent
      protein expression levels were higher in transgenic embryos derived from gBMSCs
      pDsRed2-1 compared with those derived from gFFCs-pDsRed2-1 (48.8% vs. 31.1%,
      respectively) (P < 0.01). Real-time quantitative Polymerase Chain Reaction
      analysis showed that DsRed2-1 messenger RNA expression of cloned embryos derived
      from gBMSCs was 2.24 greater than that of embryos derived from gFFCs-pDsRed2-1 (P
      < 0.01). Similarly, Western blot analysis showed that DsRed2 protein expression
      of cloned embryos derived from gBMSCs-pDsRed2-1 was 1.29 greater than that of
      embryos derived from gFFCs-pDsRed2-1 (P < 0.01). In this study, gBMSCs were also
      used for somatic cell nuclear transfer and shown to provide effective nuclear
      donor cells for breeding new genetically modified varieties of livestock.

PMID- 24679908
TI  - The affordable care act and treatment for "substance use disorders:" implications
      of ending segregated behavioral healthcare.
AB  - The Affordable Care Act (2010) and the Mental Health Parity and Addiction Equity
      Act (2008) are expected to transform substance abuse prevention and treatment in
      the United States. In this paper, we outline the potential disruption to the
      existing specialty care delivery system, and describe the opportunities for
      treatment providers and health services researchers. 

PMID- 24679909
TI  - Questions regarding thumb immobilization.

PMID- 24679911
TI  - Carpal fractures.
AB  - Carpal fractures are exceedingly rare clinical entities and are often associated
      with concomitant injuries. In this review, we focus on fractures of the carpus,
      excluding the scaphoid, and provide an update on the current consensus as to
      mechanism, diagnosis, management, outcomes, and complications after such
      injuries. 

PMID- 24679910
TI  - Blood glucose levels in diabetic patients following corticosteroid injections
      into the hand and wrist.
AB  - PURPOSE: To quantify diabetic patients' change in blood glucose levels after
      corticosteroid injection for common hand diseases and to assess which patient
      level risk factors may predict an increase in blood glucose levels. METHODS:
      Patients were recruited for this case-crossover study in the clinic of fellowship
      trained hand surgeons at a tertiary care center. Patients with diabetes mellitus
      type 1 or 2, who received a corticosteroid injection, recorded the morning
      fasting blood glucose levels for 14 days after the injection. Fasting glucose
      levels on days 1 to 7 after injection qualified as case data; levels on days 10
      to 14 provided control data. A mixed model with a priori contrasts was used to
      compare postinjection blood glucose levels with baseline levels. We used a linear
      regression model to determine patient predictors of a postinjection rise in blood
      glucose levels. RESULTS: Of 67 patients recruited for the study returned, 40
      (60%) completed blood glucose logs. There was a significant increase in fasting
      blood glucose levels after injection limited to postinjection days 1 and 2. Among
      patient risk factors in the linear regression model, type 1 diabetes and use of
      insulin each predicted a postinjection increase in blood glucose levels from
      baseline, whereas higher glycated hemoglobin levels did not predict increases.
      CONCLUSIONS: Corticosteroid injections in the hand transiently increase blood
      glucose levels in diabetic patients. Patients with type 1 diabetes and insulin
      dependent diabetics are more likely to experience this transient rise in blood
      glucose levels. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 24679912
TI  - Fracture dislocation of the finger joints.
AB  - Fracture dislocations of the hand are difficult and often unforgiving injuries.
      Keys to treatment include early recognition, stable concentric reduction, and
      protected early active range of motion maintaining joint stability. The balance
      between stability and mobility is difficult to manage; therefore, surgeons need a
      wide array of treatments to tailor management to the specific fracture pattern.
      With appropriate treatment, residual stiffness and pain can be minimized. This
      Current Concepts review aims to provide up-to-date management for proximal
      interphalangeal, distal interphalangeal, and metacarpophalangeal joint fracture
      dislocations. 

PMID- 24679913
TI  - Ulnar mammary syndrome.

PMID- 24679914
TI  - Al-Akhawayni and early differentiation between nerves and tendons.

PMID- 24679915
TI  - Cold intolerance following collagenase Clostridium histolyticum treatment for
      Dupuytren contracture.

PMID- 24679916
TI  - The elastic band (Dhaga) syndrome: physicians and surgeons be aware.

PMID- 24679917
TI  - Updated embryology of the upper limb.

PMID- 24679918
TI  - In reply.

PMID- 24679919
TI  - Identifying parameters that influence efficiency of surgical procedures.

PMID- 24679920
TI  - In reply.

PMID- 24679921
TI  - Reducing time in the analysis of Listeria monocytogenes in meat, dairy and
      vegetable products.
AB  - The microbiological standard for detection of Listeria monocytogenes relies on
      several cultural steps and requires 7 days for final confirmation, and due to
      food distribution and market demands, there is a prevailing need for an
      alternative methodology for its detection. The aim of this study was to compare
      different detection strategies based on real-time PCR (RTi-PCR) for a rapid and
      sensitive detection in an ample range of food products: raw pork and poultry
      meat, raw sheep milk cured cheese, and ready to eat lettuce salad. Four
      parameters were evaluated to reduce the time and cost for final results: the
      initial sample size (25 and 50 g), the dilution of the sample (1:3; 1:5 and 1:10
      dilutions in Half Fraser broth), the incubation times (6, 10 and 24h) and the
      bacterial DNA extraction (simple boiling of the culture after washing the
      bacterial pellet, the use of the Chelex resin, and a commercial silica column.
      The results obtained demonstrate that a combination of an incubation in Half
      Fraser for 24h of a 1:10 diluted-25 g-sample coupled to a DNA extraction using a
      commercial silica column and a real-time PCR assay detected down to 2-4 L.
      monocytogenes CFU per sample in less than 27 h in different types of food
      products. This RTi-PCR-based method is fully compatible with the ISO standard,
      providing results more rapidly and cost-effectively. The results were confirmed
      in a large number of naturally contaminated food samples with at least the same
      analytical performance as the reference method.

PMID- 24679922
TI  - Therapeutic doses of buspirone block D3 receptors in the living primate brain.
AB  - Dopamine D3 receptor (D3R) antagonists may be effective medications for multiple
      substance use disorders (SUDs). However, no selective D3R antagonists are
      currently available for clinical testing. Buspirone, originally characterized as
      a 5-HT1A partial agonist and used as an anxiolytic, also binds to D3R and D4R
      with high affinity, with lower affinity to D2R, and interferes with cocaine
      reward. Here we used PET with [11C]PHNO (D3R-preferring radioligand),
      [11C]raclopride (D2R/D3R radioligand) and [11C]NNC-112 (D1R radioligand) to
      measure occupancy of oral and parenteral buspirone in the primate brain.
      Intramuscular buspirone (0.19 and 0.5 mg/kg) blocked both [11C]PHNO and
      [11C]raclopride binding to striatum, exhibiting high occupancy (50-85%) at 15 min
      and rapid wash-out over 2-6 h. In contrast, oral buspirone (3 mg/kg)
      significantly blocked [11C]PHNO binding in D3-rich regions (globus pallidum and
      midbrain) at 3 h, but had minimal effects on [11C]raclopride binding (28-37% at 1
      h and 10% at 3 h). Buspirone did not block [11C]NNC-112. Our findings provide
      evidence that i.m. buspirone blocks D3R and D2R, whereas oral buspirone is more
      selective towards D3R blockade in vivo, consistent with extensive first pass
      metabolism and supporting the hypothesis that its metabolites (5- and 6'
      hydroxybuspirone) merit evaluation for treating SUDs. They also indicate that for
      oral buspirone to achieve greater than 80% sustained D3R occupancy, as might be
      needed to treat addiction, higher doses (at least three-fold) than those used to
      treat anxiety (maximal 60 mg) will be required. Nonetheless, based on previous
      clinical studies, these doses would be safe and well tolerated. 

PMID- 24679923
TI  - Sexual selection as a driver of population health.

PMID- 24679924
TI  - Changing landscapes, changing practice: negotiating access to sleeping sickness
      services in a post-conflict society.
AB  - For several decades, control programmes for human African trypanosomiasis (HAT,
      or sleeping sickness) in South Sudan have been delivered almost entirely as
      humanitarian interventions: large, well-organised, externally-funded but short
      term programmes with a strategic focus on active screening. When attempts to hand
      over these programmes to local partners fail, resident populations must actively
      seek and negotiate access to tests at hospitals via passive screening. However,
      little is known about the social impact of such humanitarian interventions or the
      consequences of withdrawal on access to and utilisation of remaining services by
      local populations. Based on qualitative and quantitative fieldwork in Nimule,
      South Sudan (2008-2010), where passive screening necessarily became the
      predominant strategy, this paper investigates the reasons why, among two ethnic
      groups (Madi returnees and Dinka displaced populations), service uptake was so
      much higher among the latter. HAT tests were the only form of clinical care for
      which displaced Dinka populations could self-refer; access to all other services
      was negotiated through indigenous area workers. Because of the long history of
      conflict, these encounters were often morally and politically fraught. An open
      door policy to screening supported Dinka people to 'try' HAT tests in the normal
      course of treatment-seeking, thereby empowering them to use HAT services more
      actively. This paper argues that in a context like South Sudan, where HAT control
      increasingly depends upon patient-led approaches to case-detection, it is
      imperative to understand the cultural values and political histories associated
      with the practice of testing and how medical humanitarian programmes shape this
      landscape of care, even after they have been scaled down. 

PMID- 24679925
TI  - Are preceptors adequately prepared for their role in supporting newly qualified
      staff?
AB  - OBJECTIVE: The purpose of this UK based study is to ascertain the support
      provided to preceptors and the qualities they require to carry out their role
      supporting newly qualified professionals. DESIGN: A qualitative descriptive
      approach was adopted to elicit the experiences and perceptions of the preceptors
      in practice. SAMPLE AND METHODS: A cross-section of 30 preceptors were randomised
      across 3 hospital sites within one acute Trust. Questionnaires were distributed
      with a response rate of 37% (n=11). Five preceptors participated in a semi
      structured interview (n=5). FINDINGS AND DISCUSSION: The themes that emerged from
      the analysis were lack of preparation for their role, expectations of the
      preceptors and how they perceive the role and the limitations and difficulties
      associated with being a preceptor. CONCLUSIONS: Preceptor attributes and
      programme approaches have been discussed in the existing literature although
      guidance concerning preparation and training for the role in the UK is less well
      documented. The findings of this small scale study may be useful in planning and
      developing preceptorship programmes in the future to provide sustainable support
      to develop the preceptor as well as the preceptee.

PMID- 24679926
TI  - Cognitive decline after entering a nursing home: a 22-year follow-up study of
      institutionalized and noninstitutionalized elderly people.
AB  - OBJECTIVE: The objective of this study is to compare cognitive decline of elderly
      people after entering an institution with that of elders living in the community
      with similar clinical conditions. DESIGN: The Personnes Agees QUID (PAQUID)
      cohort is a prospective population-based study which included, at baseline, 3777
      community-dwelling people aged 65 years and older. Participants were followed-up
      for 22 years. Among those who were nondemented and living at home at baseline, 2
      groups were compared: participants who entered a nursing home during study follow
      up (n = 558) and those who remained living at home (n = 3117). Cognitive decline
      was assessed with Mini-Mental State Examination (MMSE), Benton visual retention
      test, and verbal fluency Isaacs Set Test. RESULTS: After controlling for numerous
      potential confounders, including baseline MMSE and instrumental activities of
      daily living scores, incident dementia, depressive symptoms, and chronic
      diseases, nursing home placement was significantly associated with a lower score
      on MMSE between the last visit before and after institutionalization (difference
      of 2.8 points, P < .0001) and greater further cognitive decline after
      institutionalization (difference of 0.7 point per year, P < .0001). Similar
      results were found for the Benton memory test. In a second series of analysis in
      which the persons who became demented over the study follow-up were excluded, the
      results remained unchanged. CONCLUSIONS: The present study suggests that
      institutionalized elderly people present a greater cognitive decline than persons
      remaining in the community. The reasons of that decline remain unclear and may be
      related to physical and psychological effects of institutionalization in elderly
      people.

PMID- 24679928
TI  - Effects of decreasing metabolizable protein and rumen-undegradable protein on
      milk production and composition and blood metabolites of Holstein dairy cows in
      early lactation.
AB  - This study was conducted to evaluate the effects of decreasing dietary protein
      and rumen-undegradable protein (RUP) on production performance, nitrogen
      retention, and nutrient digestibility in high-producing Holstein cows in early
      lactation. Twelve multiparous Holstein lactating cows (2 lactations; 50 +/- 7 d
      in milk; 47 kg/d of milk production) were used in a Latin square design with 4
      treatments and 3 replicates (cows). Treatments 1 to 4 consisted of diets
      containing 18, 17.2, 16.4, and 15.6% crude protein (CP), respectively, with the
      18% CP diet considered the control group. Rumen-degradable protein levels were
      constant across the treatments (approximately 10.9% on a dry matter basis),
      whereas RUP was gradually decreased. All diets were calculated to supply a
      postruminal Lys:Met ratio of about 3:1. Dietary CP had no significant effects on
      milk production or milk composition. In fact, 16.4% dietary CP compared with 18%
      dietary CP led to higher milk production; however, this effect was not
      significant. Feed intake was higher for 16.4% CP than for 18% CP (25.7 vs. 24.3
      kg/d). Control cows had greater CP and RUP intakes, which resulted in higher
      concentrations of plasma urea nitrogen and milk urea nitrogen; cows receiving
      16.4 and 15.6% CP, respectively, exhibited lower concentrations of milk urea
      nitrogen (15.2 and 15.1 vs. 17.3 mg/dL). The control diet had a significant
      effect on predicted urinary N. Higher CP digestibility was recorded for 18% CP
      compared with the other diets. Decreasing CP and RUP to 15.6 and 4.6% of dietary
      dry matter, respectively, had no negative effects on milk production or
      composition when the amounts of Lys and Met and the Lys:Met ratio were balanced.
      Furthermore, decreasing CP and RUP to 16.4 and 5.4%, respectively, increased dry
      matter intake.

PMID- 24679927
TI  - Cellular communication and heterogeneity in pancreatic islet insulin secretion
      dynamics.
AB  - Coordinated pulses of electrical activity and insulin secretion are a hallmark of
      the islet of Langerhans. These coordinated behaviors are lost when beta cells are
      dissociated, which also leads to increased insulin secretion at low glucose
      levels. Islets without gap junctions exhibit asynchronous electrical activity
      similar to dispersed cells, but their secretion at low glucose levels is still
      clamped off, putatively by a juxtacrine mechanism. Mice lacking beta cell gap
      junctions have near-normal average insulin levels, but are glucose intolerant due
      to reduced first-phase and pulsatile insulin secretion, illustrating the
      importance of temporal dynamics. Here, we review the quantitative data on islet
      synchronization and the current mathematical models that have been developed to
      explain these behaviors and generate greater understanding of the underlying
      mechanisms. 

PMID- 24679929
TI  - Risk factors that affect reproductive target achievement in fertile dairy cows.
AB  - The aims of the present study were to investigate (1) the risk factors that
      influence the achievement of reproductive targets postpartum (pp) and (2) the key
      factors that influence pregnancy rate following first artificial insemination
      (AI) in dairy cows. Ninety-eight Holstein-Friesian pp cows were blood sampled
      from wk 1 to 4 pp for hematology and biochemistry. Reproductive tract health was
      assessed weekly by ultrasonography and vaginal mucus scoring. Body condition
      score (BCS), lameness score, and milk yield were assessed every 2 wk. Milk
      samples for progesterone assay were collected twice weekly and on d 4, 5, and 7
      after AI. Risk factors associated with achieving reproductive targets depended on
      (1) increased metabolic activity of the liver (increased glutamate dehydrogenase
      at calving and increased gamma-glutamyl transpeptidase in wk 4), (2) a competent
      immune system (increased neutrophils in wk 1; decreased alpha1-acid glycoprotein
      in wk 1, 2, and 3), (3) an endocrine system that was capable of responding by
      producing sufficient triiodothyronine in wk 2 and increased insulin-like growth
      factor I in wk 3 and 4, (4) a lower negative energy balance status (decreased
      nonesterified fatty acid concentration in wk 1; decreased beta-hydroxybutyrate
      concentration in wk 2; BCS loss between calving and d 28 pp <0.5), (5) good
      reproductive tract health [normal uterine scan at d 45 pp; clear vaginal mucus
      discharge at first ovulation and at d 45 pp; resumed ovarian cyclicity by the end
      of the voluntary waiting period (>= d 35 pp)], and (6) adequate diet (to ensure
      increased glutathione peroxidase in wk 2 and 3 and increased magnesium in wk 4).
      Risk factors that increased the odds of a successful first AI were previous
      ovulation(s) (odds ratio=3.17 per ovulation), BCS >2.5 at AI (odds ratio=3.01),
      and clear vaginal mucus (score=0) compared with purulent mucus (score >0) 4 d
      after first AI (odds ratio=2.99). In conclusion, this study identified key risk
      factors in the early pp period that give a higher probability of cows achieving
      their reproductive targets and of having a first-AI pregnancy.

PMID- 24679930
TI  - Hyperketonemia during lipopolysaccharide-induced mastitis affects systemic and
      local intramammary metabolism in dairy cows.
AB  - Hyperketonemia interferes with the metabolic regulation in dairy cows. It is
      assumed that metabolic and endocrine changes during hyperketonemia also affect
      metabolic adaptations during inflammatory processes. We therefore studied
      systemic and local intramammary effects of elevated plasma beta-hydroxybutyrate
      (BHBA) before and during the response to an intramammary lipopolysaccharide (LPS)
      challenge. Thirteen dairy cows received intravenously either a Na-DL-beta-OH
      butyrate infusion (n = 5) to achieve a constant plasma BHBA concentration (1.7 +/
      0.1 mmol/L), with adjustments of the infusion rates made based on immediate
      measurements of plasma BHBA every 15 min, or an infusion with a 0.9% NaCl
      solution (control; n = 8) for 56 h. Infusions started at 0900 h on d 1 and
      continued until 1700 h 2 d later. Two udder quarters were challenged with 200 MUg
      of Escherichia coli LPS and 2 udder quarters were treated with 0.9% saline
      solution as control quarters at 48 h after the start of infusion. Blood samples
      were taken at 1 wk and 2h before the start of infusions as reference samples and
      hourly during the infusion. Mammary gland biopsies were taken 1 wk before, and 48
      and 56 h (8h after LPS challenge) after the start of infusions. The mRNA
      abundance of key factors related to BHBA and fatty acid metabolism, and glucose
      transporters was determined in mammary tissue biopsies. Blood samples were
      analyzed for plasma glucose, BHBA, nonesterified fatty acid, urea, insulin,
      glucagon, and cortisol concentrations. Differences were not different for effects
      of BHBA infusion on the mRNA abundance of any of the measured target genes in the
      mammary gland before LPS challenge. Intramammary LPS challenge increased plasma
      glucose, cortisol, glucagon, and insulin concentrations in both groups but
      increases in plasma glucose and glucagon concentration were less pronounced in
      the Na-DL-beta-OH-butyrate infusion group than in controls. In response to LPS
      challenge, plasma BHBA concentration decreased in controls and decreased also
      slightly in the BHBA-infused animals because the BHBA concentration could not be
      fully maintained despite a rapid increase in BHBA infusion rate. The change in
      mRNA abundance of citrate synthase in LPS quarters was significant between the 2
      treatment groups. The results indicate that elevated circulating BHBA
      concentration inhibits gluconeogenesis before and during immune response to LPS
      challenge, likely because BHBA can replace glucose as an energy source.

PMID- 24679931
TI  - Are evaluations on young genotyped animals benefiting from the past generations?
AB  - Data sets of US Holsteins, Israeli Holsteins, and pigs from PIC (a Genus company,
      Hendersonville, TN) were used to evaluate the effect of different numbers of
      generations on ability to predict genomic breeding values of young genotyped
      animals. The influence of including only 2 generations of ancestors (A2) or all
      ancestors (Af) was also investigated. A total of 34,506 US Holsteins, 1,305
      Israeli Holsteins, and 5,236 pigs were genotyped. The evaluations were computed
      by traditional BLUP and single-step genomic BLUP, and computing performance was
      assessed for the latter method. For the 2 Holstein data sets, coefficients of
      determination (R(2)) and regression (delta) of deregressed evaluations from a
      full data set with records up to 2011 on estimated breeding values and genomic
      estimated breeding values from the truncated data sets were computed. The
      thresholds for data deletion were set by intervals of 5 yr, based on the average
      generation interval in dairy cattle. For the PIC data set, correlations between
      corrected phenotypes and estimated or genomic estimated breeding values were used
      to evaluate predictive ability on young animals born in 2010 and 2011. The
      reduced data set contained data up to 2009, and the thresholds were set based on
      an average generation interval of 3 yr. The number of generations that could be
      deleted without a reduction in accuracy depended on data structure and trait. For
      US Holsteins, removing 3 and 4 generations of data did not reduce accuracy of
      evaluations for final score in Af and A2 scenarios, respectively. For Israeli
      Holsteins, the accuracies for milk, fat, and protein yields were the highest when
      only phenotypes recorded in 2000 and later were included and full pedigrees were
      applied. Of the 135 Israeli bulls with genotypes (validation set) and daughter
      records only in the complete data set, 38 and 97 were sons of Israeli and foreign
      bulls, respectively. Although more phenotypic data increased the prediction
      accuracy for sons of Israeli bulls, the reverse was true for sons of foreign
      bulls. Also, more phenotypic data caused large inflation of genomic estimated
      breeding values for sons of foreign bulls, whereas the opposite was true with the
      deletion of all but the most recent phenotypic data. Results for protein and fat
      percentage were different from those for milk, fat, and protein yields; however,
      relatively, the changes in coefficients of determination and regression were
      smaller for percentage traits. For PIC data set, removing data from up to 5
      generations did not erode predictive ability for genotyped animals for the 2
      reproductive traits used in validation. Given the data used in this study,
      truncating old data reduces computation requirements but does not decrease the
      accuracy. For small populations that include local and imported animals,
      truncation may be beneficial for one group of animals and detrimental to another
      group. 

PMID- 24679932
TI  - Effect of replacing grass silage with red clover silage on nutrient digestion,
      nitrogen metabolism, and milk fat composition in lactating cows fed diets
      containing a 60:40 forage-to-concentrate ratio.
AB  - Diets based on red clover silage (RCS) typically increase the concentration of
      polyunsaturated fatty acids (PUFA) in ruminant meat and milk and lower the
      efficiency of N utilization compared with grass silages (GS). Four multiparous
      Finnish Ayrshire cows (108 d postpartum) fitted with rumen cannulas were used in
      a 4 * 4 Latin square design with 21-d periods to evaluate the effect of
      incremental replacement of GS with RCS on milk production, nutrient digestion,
      whole-body N metabolism, and milk fatty acid composition. Treatments comprised
      total mixed rations offered ad libitum, containing 600 g of forage/kg of diet dry
      matter (DM), with RCS replacing GS in ratios of 0:100, 33:67, 67:33, and 100:0 on
      a DM basis. Intake of DM and milk yield tended to be higher when RCS and GS were
      offered as a mixture than when fed alone. Forage species had no influence on the
      concentration or secretion of total milk fat, whereas replacing GS with RCS
      tended to decrease milk protein concentration and yield. Substitution of GS with
      RCS decreased linearly whole-tract apparent organic matter, fiber, and N
      digestion. Forage species had no effect on total nonammonia N at the omasum,
      whereas the flow of most AA at the omasum was higher for diets based on a mixture
      of forages. Replacing GS with RCS progressively lowered protein degradation in
      the rumen, increased linearly ruminal escape of dietary protein, and decreased
      linearly microbial protein synthesis. Incremental inclusion of RCS in the diet
      tended to lower whole-body N balance, increased linearly the proportion of
      dietary N excreted in feces and urine, and decreased linearly the utilization of
      dietary N for milk protein synthesis. Furthermore, replacing GS with RCS
      decreased linearly milk fat 4:0 to 8:0, 14:0, and 16:0 concentrations and
      increased linearly 18:2n-6 and 18:3n-3 concentrations, in the absence of changes
      in cis-9 18:1, cis-9, trans-11 18:2, or total trans fatty acid concentration.
      Inclusion of RCS in the diet progressively increased the apparent transfer of 18
      carbon PUFA from the diet into milk, but had no effect on the amount of 18:2n-6
      or 18:3n-3 at the omasum recovered in milk. In conclusion, forage species
      modified ruminal N metabolism, the flow of AA at the omasum, and whole-body N
      partitioning. A lower efficiency of N utilization for milk protein synthesis with
      RCS relative to GS was associated with decreased availability of AA for
      absorption, with some evidence of an imbalance in the supply of AA relative to
      requirements. Higher enrichment of PUFA in milk for diets based on RCS was
      related to an increased supply for absorption, with no indication that forage
      species substantially altered PUFA bioavailability.

PMID- 24679933
TI  - Using recursion to compute the inverse of the genomic relationship matrix.
AB  - Computing the inverse of the genomic relationship matrix using recursion was
      investigated. A traditional algorithm to invert the numerator relationship matrix
      is based on the observation that the conditional expectation for an additive
      effect of 1 animal given the effects of all other animals depends on the effects
      of its sire and dam only, each with a coefficient of 0.5. With genomic
      relationships, such an expectation depends on all other genotyped animals, and
      the coefficients do not have any set value. For each animal, the coefficients
      plus the conditional variance can be called a genomic recursion. If such
      recursions are known, the mixed model equations can be solved without explicitly
      creating the inverse of the genomic relationship matrix. Several algorithms were
      developed to create genomic recursions. In an algorithm with sequential updates,
      genomic recursions are created animal by animal. That algorithm can also be used
      to update a known inverse of a genomic relationship matrix for additional
      genotypes. In an algorithm with forward updates, a newly computed recursion is
      immediately applied to update recursions for remaining animals. The computing
      costs for both algorithms depend on the sparsity pattern of the genomic
      recursions, but are lower or equal than for regular inversion. An algorithm for
      proven and young animals assumes that the genomic recursions for young animals
      contain coefficients only for proven animals. Such an algorithm generates exact
      genomic EBV in genomic BLUP and is an approximation in single-step genomic BLUP.
      That algorithm has a cubic cost for the number of proven animals and a linear
      cost for the number of young animals. The genomic recursions can provide new
      insight into genomic evaluation and possibly reduce costs of genetic predictions
      with extremely large numbers of genotypes. 

PMID- 24679934
TI  - Use of just-about-right scales and penalty analysis to determine appropriate
      concentrations of stevia sweeteners for vanilla yogurt.
AB  - With the mainstream emergence of natural sweeteners such as stevia, which is
      available in different commercial formulations, suitability for yogurt needs to
      be validated. The present study aimed to determine the appropriate concentration
      level of 3 processed stevia sweeteners/supplements in commercial plain low-fat
      yogurt flavored with natural vanilla. Three different levels of sucrose,
      aspartame, an erythritol and 95% rebaudiana A stevia sweetener, a 95% pure mix of
      maltodextrin and steviol glycosides, and a cold water stevia extract were used in
      the study. The just-about-right level for each sweetener and consumer
      acceptability of each naturally flavored low-fat vanilla yogurt were evaluated.
      Results from penalty analysis demonstrated that only 0.7% of stevia containing
      maltodextrin and 95% steviol glycoside was necessary, whereas higher levels
      (between 4.0 to 5.5%) were more appropriate for stevia containing erythritol and
      95% rebaudiana A or cold water extract of stevia, respectively. The
      concentrations of stevia sweeteners used influenced the perceived sweetness and
      sourness. In general, consumers disliked the yogurt sweetened with stevia or
      aspartame, and neither disliked nor liked the yogurt sweetened with sucrose,
      which was largely driven by perceived sourness of the base yogurt. The findings
      underline the importance of careful selection of stevia type and concentration as
      well as optimizing yogurt cultures and fermentation conditions before product
      launch. 

PMID- 24679935
TI  - Increased blood-circulating interferon-gamma, interleukin-17, and osteopontin
      levels in bovine paratuberculosis.
AB  - Paratuberculosis-infected cattle initially develop an effective cell-mediated
      immune response that declines as the disease progresses. Blood is one of best
      sources for characterizing the inflammatory status of infected cows and for
      studying mediators related to chronic diseases. The aim of this study was to
      evaluate the cow-level association between blood cytokine concentration, the
      influence of serum on immune cell proliferation, and dairy cows naturally
      infected with Mycobacterium avium ssp. paratuberculosis (MAP). Positive animals
      (n=41) from 19 herds were selected on the basis of 2 positive fecal culture
      results and divided into 2 groups: single-positive, or serum ELISA-negative cows
      (n=32), and double-positive, or cows that gave positive results for both
      mycobacterial culture and serum ELISA (n=9). Negative animals (n=39) were
      selected from paratuberculosis-negative herds in which at least 80% of the
      animals had been diagnosed as negative by fecal culture and ELISA and that did
      not produce positive results during the 2-yr study. Analysis of plasma levels of
      the cytokines IL-4, IL-10, IL-17, IFN-gamma, and osteopontin was performed,
      revealing distinct patterns. The ELISA-positive cows with MAP shedding had
      similar plasma concentrations of IL-4 and IL-10 but elevated levels of IFN-gamma,
      IL-17, and osteopontin, which is indicative of inflammatory disease in these
      subclinical positive cows. In vitro MAP infection of bovine macrophages showed
      increased gene expression of tumor necrosis factor-alpha, IL-1beta, IL-6, IL-23,
      and transforming growth factor-beta as early as 6h postinfection for all of the
      cytokines involved in the establishment of a T-helper type-17 immune response. To
      determine the systemic influence of serum on immune cell functions,
      lymphoproliferation assays were also performed in presence of JD serum. The serum
      from shedding cows showed 15% less proliferation. These results indicate that
      infected cows have a lower systemic capacity to maintain a protective immune
      response and that, as the disease progresses, an emerging T-helper type-17 immune
      response is established. 

PMID- 24679936
TI  - Quantifying veterinarians' beliefs on disease control and exploring the effect of
      new evidence: a Bayesian approach.
AB  - The clinical beliefs (expectations and demands) of veterinarians regarding herd
      level strategies to control mastitis, lameness, and Johne's disease were
      quantified in a numerical format; 94 veterinarians working in England (UK) were
      randomly selected and, during interviews, a statistical technique called
      probabilistic elicitation was used to capture their clinical expectations as
      probability distributions. The results revealed that markedly different clinical
      expectations existed for all 3 diseases, and many pairs of veterinarians had
      expectations with nonoverlapping 95% Bayesian credible intervals. For example,
      for a 3-yr lameness intervention, the most pessimistic veterinarian was centered
      at an 11% population mean reduction in lameness prevalence (95% credible
      interval: 0-21%); the most enthusiastic veterinarian was centered at a 58%
      reduction (95% credible interval: 38-78%). This suggests that a major change in
      beliefs would be required to achieve clinical agreement. Veterinarians' clinical
      expectations were used as priors in Bayesian models where they were combined with
      synthetic data (from randomized clinical trials of different sizes) to explore
      the effect of new evidence on current clinical opinion. The mathematical models
      make predictions based on the assumption that veterinarians will update their
      beliefs logically. For example, for the lameness intervention, a 200-farm
      clinical trial that estimated a 30% mean reduction in lameness prevalence was
      predicted to be reasonably convincing to the most pessimist veterinarian; that
      is, in light of this data, they were predicted to believe there would be a 0.92
      probability of exceeding the median clinical demand of this sample of
      veterinarians, which was a 20% mean reduction in lameness. Currently, controversy
      exists over the extent to which veterinarians update their beliefs logically, and
      further research on this is needed. This study has demonstrated that
      probabilistic elicitation and a Bayesian framework are useful for evaluating the
      diversity and strength of veterinarians' clinical beliefs. The wide variations
      observed have implications for designing future projects. Although many factors
      influence disease control, nonetheless the heterogeneity in beliefs also raises
      concern over the extent to which a broadly consistent approach is currently being
      achieved; it supports the argument for more randomized clinical trials and for
      national programs to control nonstatutory endemic diseases. 

PMID- 24679937
TI  - Incorporating heifer feed efficiency in the Australian selection index using
      genomic selection.
AB  - The economic benefit of expanding the Australian Profit Ranking (APR) index to
      include residual feed intake (RFI) was evaluated using a multitrait selection
      index. This required the estimation of genetic parameters for RFI and genetic
      correlations using single nucleotide polymorphism data (genomic) correlations
      with other traits. Heritabilities of RFI, dry matter intake (DMI), and all the
      traits in the APR (milk, fat, and protein yields; somatic cell count; fertility;
      survival; milking speed; and temperament), and genomic correlations between these
      traits were estimated using a Bayesian framework, using data from 843 growing
      Holstein heifers with phenotypes for DMI and RFI, and bulls with records for the
      other traits. Heritability estimates of DMI and RFI were 0.44 and 0.33,
      respectively, and the genomic correlation between them was 0.03 and
      nonsignificant. The genomic correlations between the feed-efficiency traits and
      milk yield traits were also close to zero, ranging between -0.11 and 0.10.
      Positive genomic correlations were found for DMI with stature (0.16) and with
      overall type (0.14), suggesting that taller cows eat more as heifers. One issue
      was that the genomic correlation estimates for RFI with calving interval (ClvI)
      and with body condition score were both unfavorable (-0.13 and 0.71
      respectively), suggesting an antagonism between feed efficiency and fertility.
      However, because of the relatively small numbers of animals in this study, a
      large 95% probability interval existed for the genomic correlation between RFI
      and ClvI (-0.66, 0.36). Given these parameters, and a genetic correlation between
      heifer and lactating cow RFI of 0.67, inclusion of RFI in the APR index would
      reduce RFI by 1.76 kg/cow per year. Including RFI in the APR would result in the
      national Australian Holstein herd consuming 1.73 * 10(6) kg less feed, which is
      worth 0.55 million Australian dollars (A$) per year and is 3% greater than is
      currently possible to achieve. Other traits contributing to profitability, such
      as milk production and fertility, will also improve through selection on this
      index; for example, ClvI would be reduced by 0.53 d/cow per year, which is 96% of
      the gain for this trait that is achieved without RFI in the APR.

PMID- 24679938
TI  - Genomic evaluation, breed identification, and discovery of a haplotype affecting
      fertility for Ayrshire dairy cattle.
AB  - Genomic evaluations of dairy cattle in the United States have been available for
      Brown Swiss, Holsteins, and Jerseys since 2009. As of January 2013, 1,023
      Ayrshires had genotypes in the North American database. Evaluation accuracy was
      assessed using genomic evaluations based on 646 bulls with 2008 traditional
      evaluations to predict daughter performance of up to 180 bulls in 2012. Mean gain
      in reliability over parent average for all traits was 8.2 percentage points. The
      highest gains were for protein yield (16.9 percentage points), milk yield (16.6
      percentage points), and stature (16.2 percentage points). Twelve single
      nucleotide polymorphisms were useful for Ayrshire breed determination. Fewer
      breed-determining SNP were available for Ayrshires than for Holsteins, Jerseys,
      and Brown Swiss because of the similarity of Ayrshires and Holsteins. A haplotype
      that affects fertility was identified on chromosome 17 and traces back in the
      genotyped population to the bull Selwood Betty's Commander (born in 1953). The
      haplotype carrier frequency for genotyped Ayrshires was 26.1%. Sire conception
      rate was decreased by 4.3 +/- 2.5 percentage points for carriers of the haplotype
      as determined by 618 matings of carrier sire by carrier maternal grandsire.
      Genomic evaluations for Ayrshires were officially implemented in the United
      States in April 2013.

PMID- 24679939
TI  - Relationship between postmilking standing duration and risk of intramammary
      infection in freestall-housed dairy cows milked 3 times per day.
AB  - Recent evidence exists to suggest that the risk of subclinical mastitis,
      particularly those infections caused by environmental pathogens, in dairy cows is
      related to standing and lying patterns. The objective of this study was to
      determine the association between postmilking standing duration (PMSD) of dairy
      cows milked 3*/d and risk of intramammary infection (IMI). Four commercial
      freestall dairy herds in Eastern Ontario, milking 3*/d, were enrolled in a
      longitudinal study. Forty Holstein-Friesian cows per herd were randomly selected
      as focal animals from those cows in each herd that met our selection criteria of
      days in milk (<200 d) and somatic cell count (<100,000 cells/mL). The study
      consisted of three 28-d periods. The study began following a regularly scheduled
      Dairy Herd Improvement test with the collection of quarter-level milk samples
      from all focal animals. Bacteriology was used to confirm infection status at the
      start of the study and for determination of incidence of IMI throughout the
      study. A new IMI was defined as having a culture-positive quarter-level sample
      when the previous sample (28 d prior) had been culture negative for the pathogen
      of interest. Four sets of quarter-level milk samples were obtained for each focal
      animal. Lying behavior was recorded for 5 d after each milk sampling using data
      loggers. For these 5 d, individual milking times, production, and feeding times
      were also recorded. Postmilking standing duration was analyzed by milking event,
      with increased PMSD being positively associated with provision of fresh feed or
      freshly pushed-up feed around the time of milking, greater feed bunk space per
      cow, and lower freestall stocking density. Over the study period, 456 new IMI
      were detected, resulting in a mean herd incidence rate of 3.22 IMI per quarter
      year. Coagulase-negative staphylococci (CNS) and Corynebacterium spp. IMI were
      statistically analyzed to determine relationship with PMSD; they were the 2
      predominant pathogens representing 45 and 31% of IMI, respectively. Only CNS IMI
      was associated with PMSD. A nonlinear relationship between PMSD and incidence of
      CNS IMI was found; cows with a PMSD of 90 to 120 min were at a reduced risk for
      CNS IMI. The risk of experiencing CNS IMI was also reduced with increased
      frequency of feed push-ups and provision of fresh feed 60 min before to 90 min
      after milking and >540 min after milking. These results indicate that management
      practices that promote PMSD of 90 to 120 min, such as the provision of fresh feed
      or freshly pushed-up feed around the time of milking, providing ample feed bunk
      space per cow, and keeping freestall stocking density low, should be encouraged
      to reduce the risk of CNS IMI in freestall-housed cows milked 3*/d.

PMID- 24679940
TI  - Phase reversal technique decreases cortical stimulation time during motor
      mapping.
AB  - Neurophysiologic mapping of the primary motor cortex (PMC) is commonly used in
      supratentorial surgery. Electrical cortical stimulation is guided by anatomic
      landmarks towards the precentral gyrus, with recording of the triggered primary
      motor responses (TPMR) in the contralateral hemibody. Thus, factors such as
      distortion of the pericentral anatomy, small surgical fields, brain shifts and
      miscalibrated neuronavigational systems may lengthen the process and result in
      unnecessary stimulations, increasing the probability of triggering seizures. We
      hypothesized that central sulcus localization via the median somatosensory evoked
      potentials phase reversal technique (MSSEP PRT) accurately guides the surgeon,
      resulting in prompt identification of the PMC with minimal electrical
      stimulation. Multivariate Cox regression was used to study the impact of MSSEP
      PRT on time spent performing electrical cortical stimulation to TPMR. The
      analysis was adjusted for presence of increased cortical excitability, high motor
      thresholds, lesions close to PMC and fMRI data, in 100 consecutive standardized
      motor mapping procedures for brain tumor resection and epilepsy surgery. Phase
      reversal and change morphology of the recorded somatosensory evoked potentials
      quadrupled (hazard ratio [HR] 4.13, p<0.0001) and doubled (HR 2.14, p=0.02) the
      rate of obtaining TPMR, respectively. A 1mA increase in motor threshold decreased
      the rate by 9% (HR 0.91, p=0.0002). Afterdischarges triggered before TPMR and
      lesions in close proximity to PMC decreased the rate of TPMR by 76% (HR 0.23,
      p<0.0001) and 48% (HR 0.52, p=0.04), respectively. Informative PRT decreases
      stimulation time. Afterdischarges triggered before TPMR, high motor thresholds
      and lesions close to the PMC increase it. 

PMID- 24679941
TI  - Sublobar resection for lung adenocarcinoma meeting node-negative criteria on
      preoperative imaging.
AB  - BACKGROUND: This study evaluated the usefulness of sublobar resection for
      patients with clinical stage IA lung adenocarcinoma that met our proposed node
      negative criteria: solid tumor size of less than 0.8 cm on high-resolution
      computed tomography or maximum standardized uptake value of less than 1.5 on
      [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography.
      METHODS: A multicenter database of 618 patients with completely resected clinical
      stage IA lung adenocarcinoma who underwent preoperative high-resolution computed
      tomography and [18F]-fluoro-2-deoxy-d-glucose positron emission
      tomography/computed tomography was used to evaluate the surgical results of
      sublobar resection for patients who met our node-negative criteria. RESULTS: No
      patient who met the node-negative criteria had any pathological lymph node
      metastasis. Recurrence-free survival (RFS) and overall survival (OS) rates at 5
      years were significantly higher for patients who met the node-negative criteria
      (RFS: 96.6%; OS: 95.9%) than for patients who did not (RFS: 75.5%, p<0.0001; OS:
      83.1%, p<0.0001). Among patients who met the node-negative criteria, RFS and OS
      rates at 5 years were not significantly different between those who underwent
      lobectomy (RFS: 96.0%; OS: 95.9%) and those who underwent sublobar resection
      (RFS: 97.2%, p=0.94; OS: 95.9%, p=0.98). Of 264 patients with T1b (2-cm to 3-cm)
      tumors, 106 (40.2%) met the node-negative criteria. CONCLUSIONS: Sublobar
      resection without systematic nodal dissection is feasible for clinical stage IA
      lung adenocarcinoma that meets the above-mentioned node-negative criteria. Even a
      T1b tumor, which is generally unsuitable for intentional sublobar resection, can
      be a candidate for sublobar resection if it meets these node-negative criteria.

PMID- 24679942
TI  - Association of n-3 polyunsaturated fatty acids with soluble thrombomodulin as a
      marker of endothelial damage: a cross-sectional pilot study.
AB  - BACKGROUND: Soluble thrombomodulin (sTM) is a useful marker of vascular
      endothelial damage. Although n-3 polyunsaturated fatty acids (n-3 PUFAs)
      (eicosapentaenoic acid: EPA; docosahexaenoic acid: DHA) have various
      cardiovascular protective effects, their effect in preventing vascular
      endothelial damage remains unclear. Furthermore, little is known about the
      association of EPA and DHA with sTM using the cross-sectional study method.
      METHODS AND RESULTS: This pilot study was designed as a hospital-based cross
      sectional study to investigate the relationships between serum n-3 PUFA levels
      and sTM level in patients with the presence of one or more risk factors for
      atherosclerosis. Of the 534 sequential patients who had routinely been registered
      to a study cohort of our institute, 324 patients without chronic kidney disease
      (because sTM is eliminated by renal excretion and the serum sTM level is
      increased by renal dysfunction) were enrolled in this study. In a multivariate
      analysis after adjustment for atherosclerotic risk factors, elevated EPA+DHA
      level was an independent variable of decreased sTM level (beta=-0.183, p=0.0006).
      The serum levels of EPA and DHA showed a strong correlation (r=0.736, p<0.0001);
      however, multivariate analysis including EPA and DHA revealed that serum DHA
      (beta=-0.243, p=0.003), but not serum EPA (beta=0.049, p=0.538), was identified
      as an independent negative determinant of sTM level. CONCLUSION: Although there
      are numerous unresolved issues in regard to the differences in the cardiovascular
      protective effects between EPA and DHA, DHA may be associated with a decrease in
      sTM. A large-scale trial would be warranted to demonstrate whether the beneficial
      effect of n3-PUFAs therapy on endothelial damage and improvement of endothelial
      function might also result in fewer clinical cardiovascular events.

PMID- 24679943
TI  - Clinical outcomes and causes of death in Japanese patients with long-term
      inferior vena cava filter implants and deep vein thrombosis.
AB  - BACKGROUND AND PURPOSE: We assessed the causes of death and efficacy of permanent
      inferior vena cava (IVC) filters for preventing new pulmonary embolisms (PE) in
      Japanese deep vein thrombosis (DVT) patients with or without PE. METHODS AND
      SUBJECTS: We studied the clinical outcomes during the follow-up period of 1 day
      to 9 years (median: 18 months; mean: 28 months) in 66 of 72 consecutive patients
      (44 with acute PE, 27 with intrapelvic DVT, and 1 with floating femoral vein
      thrombosis). Fifty of 66 patients received anticoagulant therapy after the filter
      placement. RESULTS: Five patients died within 1 month (median 9 days) after the
      filter placement: three from recurrence of PE, one from cancer, and one from
      sepsis. Two of the three patients with recurrence of PE had preexisting
      intracardiac thrombi in the right atrium or main pulmonary artery before filter
      implantation. Ten patients died from the underlying disease (cancer: 7; brain
      hemorrhage: 1; amyotrophic lateral sclerosis: 1; pneumonia: 1) over 1 month after
      the filter placement (median follow-up period: 21 months). No new symptomatic PE
      recurrence was observed over 1 month after the filter placement. The 61 patients
      with long-term follow-up had no deterioration of DVT, and all the 31 patients who
      underwent multi-slice computed tomography showed no PE recurrence or filter
      thrombus occlusion, fracture, or migration. CONCLUSIONS: Underlying diseases and
      preexisting intracardiac thrombi may be the determining factors for the prognosis
      of DVT patients. Permanent IVC filters with anticoagulant therapy may be
      effective for preventing death from new PE in Japanese DVT patients.

PMID- 24679944
TI  - Transplacental passage of vancomycin from mother to neonate.
AB  - OBJECTIVE: The objective of the study was to analyze a large number of patients
      receiving vancomycin chemoprophylaxis and evaluate the maternal and neonatal cord
      blood levels at the time of delivery. STUDY DESIGN: Every mother who entered
      labor with a positive group B streptococcal culture and a high-risk penicillin
      allergy with resistance to clindamycin or unknown sensitivity was consented to
      participate in the study. In the initial phase of the study, patients received
      the standard intravenous dose of 1 g every 12 hours. Based on the results, this
      was changed to a dosing of 15 mg/kg every 12 hours in the second phase and then
      further modified to 20 mg/kg every 8 hours in the third phase. Maternal and cord
      blood vancomycin levels were obtained at delivery and evaluated. RESULTS: A total
      of 55 patients consented to participate in the study, with 31 in phase I, 12 in
      phase II, and 12 in phase III. For the standard-dosing phase I group, only 32% of
      maternal and 9% of cord blood samples were therapeutic at delivery. For phase II,
      50% of maternal and 33% of cord blood values were therapeutic; however, in phase
      III, 83% of mothers and neonates had therapeutic levels at the time of delivery.
      CONCLUSION: With standard dosing, only 9% of neonates have therapeutic vancomycin
      levels at delivery. By using a regimen of 20 mg/kg intravenous every 8 hours
      (maximum individual dose 2 g), the newborn therapeutic level increases above 80%.
      The pharmacological pattern shows that transplacental passage occurs with fetal
      levels equaling maternal levels, but transplacental transport is somewhat slow in
      both directions.

PMID- 24679945
TI  - The utility score of epilepsy with partial seizure measured by TTO, VAS, and EQ
      5D in the general Korean population.
AB  - PURPOSES: This study aimed to measure utilities, which are quantitative terms
      incorporating preferences, for various health states of epilepsy with partial
      seizure in the general population in South Korea. It also aimed to find socio
      demographic characteristics associated with the utility scores. METHODS: Utility
      scores using Time Trade-Off (TTO), Visual Analog Scale (VAS), and EuroQol five
      Dimension (EQ-5D) were obtained from 300 people aged 16 and over by face-to-face
      interviews. We measured utilities for three hypothetical health states of
      epilepsy for which scenarios were defined based on the frequency of partial
      seizure: seizure-free, seizure reduction, and withdrawal. We compared utilities
      with varying seizure frequency using a repeated-measures ANOVA, and analyzed the
      association between utilities and socio-demographic characteristics using a
      generalized estimating equation (GEE). RESULTS: The mean utility scores for
      withdrawal state, seizure reduction state, and seizure-free state were 0.303,
      0.493, and 0.899, respectively, when measured by TTO. VAS yielded the mean
      utility scores of 0.211, 0.424, and 0.752 for respective health states, and
      corresponding scores with EQ-5D were 0.261, 0.645, and 0.959. The utility scores
      for the three health states were statistically different in TTO, VAS, and EQ-5D.
      The withdrawal state had the lowest utility scores. There were differences in
      mean utilities for the three health states across the three methods. Utilities by
      EQ-5D tended to have higher values than those by TTO and VAS. Utilities by VAS
      had the lowest values. In GEE analysis, the severity of epilepsy and household
      income were significantly related to utility scores. CONCLUSION: The withdrawal
      state of epilepsy had the lowest utility value and the seizure-free state had the
      highest by all three techniques of utility measurement used. There were
      significant differences in utilities between one severity level of epilepsy and
      another. Utility was associated with household income and the severity of
      disease. Utility scores for distinct epilepsy states obtained in this study could
      facilitate health economic analyses of epilepsy treatments and thus help decision
      making in resource allocation.

PMID- 24679946
TI  - Effect of antiepileptic therapy on trace elements status in Indian population in
      a tertiary care hospital from northern India: a cross sectional study.
AB  - AIM: Conventional antiepileptics (AEDs) have been shown to alter the homeostasis
      of copper, zinc, and selenium in persons with epilepsy (PWE). The effects of
      newer AEDs on trace elements have not been addressed yet. This cross-sectional
      study evaluated trace elements and electrolytes status in PWE on conventional and
      newer AEDs treatment. METHODS: A total of 307 adult persons with epilepsy and 42
      healthy controls were recruited. Panels of ten trace elements estimated by
      inductively coupled plasma-atomic emission spectrometry, electrolytes, liver and
      renal function status were compared among subjects grouped according to the
      monotherapy of AEDs and type of conventional and newer AEDs. RESULTS: Out of the
      total 307 PWE, 171 were on monotherapy [valproic acid (VPA) (n=50), carbamazepine
      (n=47), phenytoin (n=49), levetiracetam (n=21), lamotrigine (n=4)]. AEDs
      monotherapy groups had no significant difference in the trace element levels,
      except higher nickel level in levetiracetam group and low iron level in
      lamotrigine group compared to VPA group. Compared to control [zinc level 698.0
      (367.8-3084.4)ng/ml], levetiracetam group had higher zinc [1293.1 (997.7
      2419.7)ng/ml, p<0.0001], selenium, copper, iron, aluminium, cadmium, cobalt, and
      nickel levels; similar manganese and lead levels. Other monotherapy groups were
      having similar metal levels as that of levetiracetam group except nickel, iron,
      lead, and selenium levels. CONCLUSION: Trace element status was significantly
      altered with both conventional and newer antiepileptic drugs as compared to
      control; however, there was not much difference in between conventional and new
      drug treated groups. Prospective studies will address its impact on treatment
      response and adverse effect profile. CTRI REGISTRATION NUMBER:
      REF/2013/03/004819.

PMID- 24679947
TI  - Drug-resistant focal sleep related epilepsy: results and predictors of surgical
      outcome.
AB  - In this study we report the results of surgery in a large population of patients
      affected by drug-resistant focal sleep related epilepsy (SRE) and the identified
      prognostic factors. We conducted a retrospective analysis of a case series of 955
      patients operated on for drug-resistant focal epilepsy from 1997 to 2009. Ninety
      five patients with focal SRE and a follow-up of at least 2 years were identified.
      Presurgical, surgical and histopathological variables were analyzed. Risk of
      seizures recurrence was assessed by univariate and multivariate analysis. Mean
      age at epilepsy onset was 5.6 +/- 4.9 years. MRI revealed a focal abnormality in
      78.9% of cases. Sixty-two percent of patients required a Stereo-EEG
      investigation. The cortical resection involved the frontal lobe in 61.1% of
      cases, while in 38.9% an extrafrontal resection was performed. Focal cortical
      dysplasia (FCD) type II was the most frequent histopathological finding. Mean
      postoperative follow-up was 82.3 months. Seventy-three patients (76.8%) were in
      Engel's class I. At univariate analysis, variables associated with a favorable
      outcome were: absence of Stereo-EEG investigation; positive MRI; complete removal
      of the epileptogenic zone (EZ); presence of FCD type II and FCD type IIb. A
      diagnosis of FCD type I was associated with postoperative recurrence of seizures.
      Multivariate analysis identified the complete removal of the EZ and FCD type I as
      independent predictors of a favorable and unfavorable outcome respectively. SRE
      can frequently originate outside the frontal lobe and a favorable surgical
      outcome is achieved in three-fourths of cases independently from the location of
      the EZ.

PMID- 24679948
TI  - Syncing your brain: electric currents to enhance cognition.
AB  - Contemporary studies in cognitive neuroscience demonstrate that cognitive
      performance can be enhanced by applying exogenous low-intensity electric currents
      to the brain. These findings have resulted in a widespread interest from both
      scientists and popular media, particularly, regarding the host of possible
      applications in everyday life functioning. I discuss here the significance and
      current challenges of low-intensity electric current stimulation in enhancing
      cognitive performance. 

PMID- 24679949
TI  - Surfactant-free switchable emulsions using CO2-responsive particles.
AB  - Surfactant-free emulsions are prepared using bi-wetting particles which occupy
      the oil-water interface to effectively reduce the oil-water interfacial area. The
      equilibrium position of the particle at the interface is determined by its
      wettability. CO2-reponsive chemical functional groups are grafted onto the
      surface of silica particles. Particles with only CO2-switchable functional groups
      are capable of stabilizing oil-in-water emulsions. Particles prepared with both
      CO2-responsive and hydrophobic chemical functional groups on its surface are
      capable of stabilizing water-in-oil emulsions. Emulsion stability is disturbed
      when the wettability of the stabilizing particle is altered by introducing CO2
      gas to the biphasic mixture, leading to phase separation of emulsions prepared
      using the functionalized particles. The emulsion stability can be re-established
      by the removal of CO2 through air sparging. The presence of CO2 imposes positive
      surface charge to the responsive particles, increasing wettability and,
      consequently, the ability of the particles to destabilize emulsions. 

PMID- 24679950
TI  - Protein kinase Mzeta is involved in the modulatory effect of fluoxetine on
      hippocampal neurogenesis in vitro.
AB  - The efficacy of chronic selective serotonin reuptake inhibitors (SSRIs) on
      depression is paralleled by the recovery of deficits in hippocampal neurogenesis
      related to sustained stress and elevated glucocorticoids. Previous studies have
      shown that atypical protein kinase C (aPKC) is implicated in the regulation of
      neurogenesis and the antidepressant response. Whether the specific aPKC isoforms
      (PKCzeta, PKMzeta and PKCiota) are involved in SSRI-induced hippocampal
      neurogenesis and the underlying mechanisms is unknown. The present study shows
      that PKMzeta and PKCiota but not PKCzeta are expressed in rat embryonic
      hippocampal neural stem cells (NSCs), whereas PKMzeta but not PKCiota expression
      is increased by the SSRI fluoxetine both in the absence and presence of the
      glucocorticoid receptor agonist dexamethasone. PKMzeta shRNA significantly
      decreased neuronal proliferation and neuron-oriented differentiation, increased
      NSC apoptosis, and blocked the stimulatory effect of fluoxetine on NSC
      neurogenesis. Fluoxetine significantly increased PKMzeta expression in
      hippocampal NSCs in a 5-hydroxytryptamine-1A (5-HT1A) receptor-dependent manner
      in both the absence and presence of dexamethasone. The PKMzeta peptide blocker
      ZIP and MEK inhibitor U0126 significantly inhibited the increase in extracellular
      signal-regulated kinase 1/2 and cyclic adenosine monophosphate response element
      binding protein phosphorylation in the mitogen-activated protein kinase (MAPK)
      pathway and hippocampal NSC neurogenesis in response to fluoxetine and the 5-HT1A
      receptor agonist 8-OH DPAT. Collectively, our results suggest that the SSRI
      fluoxetine increases hippocampal NSC neurogenesis via a PKMzeta-mediated
      mechanism that links 5-HT1A receptor activation with the phosphorylation of the
      downstream MAPK signaling pathway. 

PMID- 24679951
TI  - A pilot study of adjuvant chemotherapy with irinotecan and cisplatin for
      completely resected high-grade pulmonary neuroendocrine carcinoma (large cell
      neuroendocrine carcinoma and small cell lung cancer).
AB  - BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung
      cancer (SCLC) are recognized as high-grade neuroendocrine carcinomas (HGNEC) of
      the lung. In patients with completely resected HGNEC, platinum-based adjuvant
      chemotherapy may be considered. However, the optimum chemotherapy regimen has not
      been determined. We conducted a multicenter single-arm phase II trial to evaluate
      irinotecan and cisplatin in postoperative adjuvant chemotherapy for HGNEC
      patients. PATIENTS AND METHODS: Patients with completely resected stage I-IIIA
      HGNEC received four cycles of irinotecan (60 mg/m(2), day 1, 8, 15) plus
      cisplatin (60 mg/m(2), day 1). This regimen was repeated every 4 weeks. The
      primary endpoint was the rate of completion of chemotherapy (defined as having
      undergone three or four cycles), and secondary endpoints were the rate of 3-year
      relapse-free survival (RFS), rate of 3-year survival and toxicities. RESULTS:
      Forty patients were enrolled between September 2007 and April 2010. Patients'
      characteristics were: median age (range) 65 [45-73] years; male 85%; ECOG-PS 1
      60%; LCNEC 57% and SCLC 43%; stage IA/IB/IIB/IIIA 32/35/8/5%; 95% received
      lobectomy. The rate of completion of chemotherapy was 83% (90%C.I.; 71-90%). The
      rate of overall survival at 3 years was estimated at 81%, and that of RFS at 3
      years was 74%. The rates of overall survival and RFS at 3 years were 86 and 74%
      among 23 LCNEC patients, and 74 and 76% among 17 SCLC patients, respectively.
      Nineteen patients (48%) experienced grade 3 or 4 neutropenia, but only five
      patients (13%) developed febrile neutropenia. Two patients (5%) developed grade 3
      diarrhea, and four patients (10%) had grade 3 nausea. No treatment-related deaths
      were observed in this study. All 40 specimens were also diagnosed as HGNEC by
      central pathological review. CONCLUSIONS: The combination of irinotecan and
      cisplatin as postoperative adjuvant chemotherapy was feasible and possibly
      efficacious for resected HGNEC.

PMID- 24679952
TI  - A genetic sequence variant (GSV) at susceptibility loci of 5p15.33 (TERT-CLPTM1L)
      is associated with survival outcome in locally advanced and metastatic non-small
      cell lung cancer (NSCLC).
AB  - INTRODUCTION: Lung cancer is a leading cause of cancer-related mortality in North
      America. In addition to tobacco smoking, inherited genetic factors can also
      influence the development of lung cancer. These genetic factors may lead to
      biologically distinct subsets of cancers that have different outcomes. We
      evaluated whether genetic sequence variants (GSVs) associated with lung cancer
      risk are associated with overall survival (OS) and progression-free survival
      (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients. METHODS: A
      total of 20 candidate GSVs in 12 genes previously reported to be associated with
      lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC.
      Multivariate Cox proportional hazard models adjusted for potential clinical
      prognostic factors were generated for OS and PFS. RESULTS: After taking into
      account multiple comparisons, one GSV remained significant: rs4975616 on
      chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio
      (aHR) for OS was 0.75 (0.69-0.91), p = 0.002; for PFS aHR was 0.74 (0.62-0.89), p
      < 0.001 for each protective variant allele. Results were similar in both Stage
      III (OS: aHR = 0.70; PFS: aHR = 0.71) and Stage IV patients (OS: aHR = 0.81; PFS:
      aHR = 0.77). CONCLUSION: A GSV on 5p15.33 is not only a risk factor for lung
      cancer but may also be associated with survival in patients with late stage
      NSCLC. If validated, GSVs may define subsets of patients with different risk and
      prognosis of NSCLC.

PMID- 24679953
TI  - High resolution CT in differentiating minimally invasive component in early lung
      adenocarcinoma.
AB  - OBJECTIVES: To analyze high-resolution computed tomography (HRCT) appearances of
      early lung adenocarcinoma and evaluate HRCT in the differentiation of minimally
      invasive component in early lung adenocarcinoma. MATERIALS AND METHODS: HRCT
      appearances of 140 nodules (less than 2 cm in diameter) of early lung
      adenocarcinoma were reviewed retrospectively. All these nodules were proven by
      surgery and pathology including 60 nodules of minimally invasive adenocarcinoma
      (MIA) and 80 nodules of preinvasive lesion (PL). HRCT features of two groups of
      lung nodules, including shape, margin, pattern, diameter, diameter of solid
      component, vascular changes, air bronchogram, vacuole, pleural indentation and
      multiplicity were analyzed and compared using univariate logistic regression
      analysis. Attenuation values of pure ground-glass nodule, pure ground-glass
      component and solid component of mixed ground-glass nodule were compared by using
      unpaired t-test or Wilcoxon rank-sum test. RESULTS: The statistically significant
      differences were found in shape, margin, pattern, diameter, diameter of solid
      component, pulmonary vein changes, air bronchogram and pleural indentation (Odds
      ratio [OR] = 3.115 [P = 0.001], OR = 3.754 [P = 0.011], OR = 9.815 [P = 0.000],
      OR = 1.306 [P = 0.000], OR = 1.361 [P = 0.031], OR= 6.971 [P = 0.000], OR = 6.167
      [P=0.000], OR = 2.296 [P = 0.027], respectively). The statistically significant
      difference was also found in attenuation value of solid component (t = 3.702, P =
      0.000). By multivariate logistic analysis, attenuation value of solid component
      was significantly associated with MIA (OR = 1.005, P = 0.032). MIA was more often
      a larger, lobulated or irregular, mixed ground-glass nodule with a solid
      component larger than 5 mm, and higher attenuation values. In addition, MIA often
      had an abnormality in pulmonary vein, air bronchogram and pleural indentation.
      CONCLUSIONS: HRCT can demonstrate the morphological features of early lung
      adenocarcinoma and identify minimally invasive component.

PMID- 24679954
TI  - Surgical planning, three-dimensional model surgery and preshaped implants in
      treatment of bilateral craniomaxillofacial post-traumatic deformities.
AB  - PURPOSE: The purpose of the present study was to explore the treatment and
      outcomes of bilateral craniomaxillofacial post-traumatic deformities with
      surgical planning, 3-dimensional (3D) model surgery, and preshaped implants.
      MATERIALS AND METHODS: We analyzed the preoperative computed tomography (CT) data
      and designed preliminary surgical plans for 3 patients with bilateral
      craniomaxillofacial post-traumatic deformities. 3D resin skull models were
      produced using rapid prototyping technology, and 3D model surgery was performed
      to determine the location, reduction direction, and shift distance of the
      osteotomy and to optimize the surgical plans. Titanium plates or mesh were
      preshaped on the models and then implanted into the patients. The complications,
      symmetry of the maxillofacial regions, mouth opening, and occlusion were observed
      1 month postoperatively. RESULTS: The patients had good recovery of their facial
      contour, occlusion, and mouth opening and acceptable symmetry of the bilateral
      maxillofacial regions. No complications were observed. CONCLUSIONS: The
      combination of surgical planning, 3D model surgery, and preshaped implants can
      provide surgical accuracy and efficiency and good therapeutic outcomes in the
      treatment of bilateral craniomaxillofacial post-traumatic deformities.

PMID- 24679955
TI  - Self-mutilation of the lower lip in a child with dystonia secondary to
      megalencephalic leukoencephalopathy treated with botox injections: a case report.
AB  - PURPOSE: We report the case of a 10-year old boy who had been diagnosed with
      megalencephalic leukoencephalopathy several years earlier. Because of the
      patient's oral dystonic activity, a traumatic, nonhealing, chronic ulcer had
      developed on his lower lip. MATERIALS AND METHODS: Botox-A was injected into the
      mentalis, orbicularis oris, and bilateral masseter muscles. RESULTS: The patient
      showed decreased dystonia and gradual complete healing of the traumatic ulcer of
      the lower lip. CONCLUSIONS: The treatment of patients with self-mutilation to the
      lips will often be difficult. Traditionally, patients have been treated with
      various medications, oral appliances, and even tooth extraction. The results of
      the present case report suggest that Botox should be considered as a possible
      first-line strategy, along with oral appliances.

PMID- 24679956
TI  - Computed tomography for the diagnosis of mandibular invasion caused by head and
      neck cancer: a systematic review comparing contrast-enhanced and plain computed
      tomography.
AB  - PURPOSE: To detect the diagnostic efficacy of computed tomography (CT) in
      distinguishing mandibular invasion caused by head and neck cancer and to compare
      the accuracy of contrast-enhanced and plain CT in the diagnosis. MATERIALS AND
      METHODS: Studies designed as cohort studies that detected the diagnostic efficacy
      of CT on mandibular invasion (including bone cortex and bone marrow invasion) and
      mandibular medullary alone (bone marrow invasion) were included. The included
      studies were required to use the pathologic diagnosis as the reference standard
      and reported true-positive, false-positive, false-negative, true-positive, and
      related data. Thirteen databases were electronically and manually searched to
      retrieve any possible related studies. Two reviewers independently conducted the
      study inclusion, data extraction, and assessment of the quality of the included
      studies. Meta-diSc, version 1.4, and STATA, version 11.0, were used to conduct
      the meta-analysis. RESULTS: A total of 30 studies with 1459 patients were
      included in the present study. Of those patients, 1,257 underwent CT and were
      accounted for in the meta-analysis. Of the included studies, 1 had a low risk and
      6 had a high risk of bias; 23 studies had an unclear risk of bias. Meta
      regression showed that the slight clinical heterogeneity did not influence the
      outcome (P > .10). The meta-analysis showed that CT for the diagnosis of
      mandibular invasion had a pooled sensitivity of 0.72, specificity of 0.90,
      positive likelihood ratio (+LR) of 5.33, negative likelihood ratio (-LR) of 0.36,
      diagnostic odds ratio (DOR) of 21.41, area under the curve (AUC) of 0.9022, and
      Q* (the value of the sensitivity or specificity when the sensitivity equals the
      specificity on the summary receiver operating characteristics curve) of 0.8336.
      The CT findings for mandibular medullar invasion had a sensitivity of 0.81,
      specificity of 0.85, +LR of 4.76, -LR of 0.24, DOR of 29.49, AUC of 0.9240, and
      Q* of 0.8580. No statistical significance was found in the sensitivity (P =
      .809), specificity (P = .27), AUC (P = .4296), and Q* (P = .4277) between the
      contrast-enhanced and plain CT scans. CONCLUSIONS: The present clinical evidence
      has shown that CT had an acceptable diagnostic value in detecting mandibular
      invasion caused by head and neck cancer. The high specificity of CT predicted it
      would be helpful when it was used to confirm the clinical diagnosis of bone
      invasion. Contrast-enhanced and plain CT scans had a similar diagnostic efficacy.

PMID- 24679957
TI  - Patient-specific polyetheretherketone facial implants in a computer-aided
      planning workflow.
AB  - PURPOSE: In the present study, we report an innovative workflow using
      polyetheretherketone (PEEK) patient-specific implants for esthetic corrections in
      the facial region through onlay grafting. The planning includes implant design
      according to virtual osteotomy and generation of a subtraction volume. The
      implant design was refined by stepwise changing the implant geometry according to
      soft tissue simulations. MATERIALS AND METHODS: One patient was scanned using
      computed tomography. PEEK implants were interactively designed and manufactured
      using rapid prototyping techniques. Positioning intraoperatively was assisted by
      computer-aided navigation. Two months after surgery, a 3-dimensional surface
      model of the patient's face was generated using photogrammetry. Finally, the
      Hausdorff distance calculation was used to quantify the overall error,
      encompassing the failures in soft tissue simulation and implantation. RESULTS:
      The implant positioning process during surgery was satisfactory. The simulated
      soft tissue surface and the photogrammetry scan of the patient showed a high
      correspondence, especially where the skin covered the implants. The mean total
      error (Hausdorff distance) was 0.81 +/- 1.00 mm (median 0.48, interquartile range
      1.11). The spatial deviation remained less than 0.7 mm for the vast majority of
      points. CONCLUSIONS: The proposed workflow provides a complete computer-aided
      design, computer-aided manufacturing, and computer-aided surgery chain for
      implant design, allowing for soft tissue simulation, fabrication of patient
      specific implants, and image-guided surgery to position the implants. Much of the
      surgical complexity resulting from osteotomies of the zygoma, chin, or mandibular
      angle might be transferred into the planning phase of patient-specific implants.

PMID- 24679958
TI  - Strategic use of serology for the diagnosis of bovine tuberculosis after
      intradermal skin testing.
AB  - Diagnostic tests based on cell-mediated immunity are used in programmes for
      eradication of bovine tuberculosis (Mycobacterium bovis). Serological assays
      could be applied as ancillary methods to detect infected animals. Our objective
      was to evaluate two serological techniques: M. bovis Ab Test (IDEXX, USA) and
      EnferplexTM TB assay (Enfer, Ireland) in animals tested simultaneously with the
      single and comparative intradermal tests and the interferon-gamma assay. This
      work was performed at two stages. First, a preliminary panel of samples collected
      prior to intradermal tests from tuberculosis-free (n=60) and M. bovis-infected
      herds (n=78) was assayed, obtaining high specificity: 100% (M. bovis Ab Test) and
      98.3% (Enferplex TB assay) but low sensitivity (detection of M. bovis infected
      animals): 23.9% (M. bovis Ab Test) and 32.6% (Enferplex TB assay). Subsequently,
      the use of serological techniques was further studied in two herds with M. bovis
      infection (n=77) using samples collected prior to, and 72 h and 15 days after PPD
      inoculation. The highest level of detection of infected animals for serology was
      achieved at 15 days post-intradermal tests taking advantage of the anamnestic
      effect: 70.4% and 85.2% in herd A, and 66.7% and 83.3% in herd B, using M. bovis
      Ab Test and Enferplex TB assay, respectively. Quantitative results (average
      values obtained with M. bovis Ab Test ELISA and degree of positivity obtained
      with Enferplex TB assay) were higher in animals showing lesions compatible with
      tuberculosis. No significant differences were observed in the number of confirmed
      infected animals detected with either serological technique.

PMID- 24679959
TI  - Experimental Schmallenberg virus infection of pigs.
AB  - Schmallenberg virus (SBV) is a newly emerged virus responsible for an acute non
      specific syndrome in adult cattle including high fever, decrease in milk
      production and severe diarrhea. It also causes reproductive problems in cattle,
      sheep and goat including abortions, stillbirths and malformations. The role of
      pigs in the epidemiology of SBV has not yet been evaluated while this could be
      interesting seen their suggested role in the epidemiology of the closely related
      Akabane virus. To address this issue, four 12 week old seronegative piglets were
      subcutaneously infected with 1 ml of SBV infectious serum (FLI) and kept into
      contact with four non-infected piglets to examine direct virus transmission.
      Throughout the experiment blood, swabs and feces samples were collected and upon
      euthanasia at 28 dpi different organs (cerebrum, cerebellum, brain stem, lung,
      liver, iliac lymph nodes, kidney and spleen) were sampled. No clinical impact was
      observed and all collected samples tested negative for SBV in rRT-PCR. Despite
      the absence of viremia and virus transmission, low and short lasting amounts of
      neutralizing antibodies were found in 2 out of 4 infected piglets. The limited
      impact of SBV infection in pigs was further supported by the absence of
      neutralizing anti-SBV antibodies in field collected sera from indoor housed
      domestic pigs (n=106). In conclusion, SBV infection of pigs can induce
      seroconversion but is ineffective in terms of virus replication and transmission
      indicating that pigs have no obvious role in the SBV epidemiology.

PMID- 24679961
TI  - Antimicrobial resistance determinants in Staphylococcus spp. recovered from birds
      of prey in Portugal.
AB  - Antibiotic resistance among wild animals represent an emerging public health
      concern. The objective of this study was to analyze the staphylococcal nasal
      microbiota in birds of prey and their content in antimicrobial resistance
      determinants. Nasal samples from 16 birds of prey were collected, swabs were
      dipped and incubated into BHI broth [6.5% NaCl] and later seeded on manitol salt
      agar and oxacillin-resistance screening agar base media. Staphylococcal colonies
      were isolated from both media and were identified by biochemical and molecular
      methods. Susceptibility testing to 18 antimicrobial agents was performed by disk
      diffusion method. Six of the 16 tested animals carried staphylococci (37.5%) and
      7 isolates of the following species were recovered: Staphylococcus aureus,
      Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus sciuri
      rodentium, Staphylococcus cohnii urealitycum, and Staphylococcus gallinarum. The
      S. aureus isolate was penicillin-resistant (with blaZ gene) but methicillin
      susceptible and was ascribed to spa-type t012, sequence-type ST30 and agr-type
      III. The S. epidermidis isolate carried blaZ, mecA, mrs(A/B), mphC, tet(K), drfA,
      and fusC genes, ica operon, and was typed as ST35. The genes ant6'-Ia, tet(K),
      tet(L), dfrG, cat221, cat194, and cat223 were detected in S. saprophyticus or S.
      gallinarum isolates. Birds of prey seem to be a natural reservoir of S. aureus
      and coagulase-negative staphylococci resistant to multiple antibiotics. Due to
      the convergence between habitats, the contact between wildlife, other animals and
      humans is now more common and this involves an increased possibility of
      interchange of these microorganisms in the different ecosystems. 

PMID- 24679960
TI  - The prevalence and genetic diversity of group A rotaviruses on pig farms in the
      Mekong Delta region of Vietnam.
AB  - Group A rotaviruses (ARoVs) are a common cause of severe diarrhea among children
      worldwide and the cause of approximately 45% of pediatric hospitalizations for
      acute diarrhea in Vietnam. ARoVs are known to cause significant economic losses
      to livestock producers by reducing growth performance and production
      efficiencies, however little is known about the implications of asymptomatic
      endemic circulation of ARoV. We aimed to determine the prevalence and predominant
      circulating genotypes of ARoVs on pig farms in a southern province of Vietnam. We
      found overall animal-level and farm-level prevalence of 32.7% (239/730) and 74%
      (77/104), respectively, and identified six different G types and 4 P types in
      various combinations (G2, G3, G4, G5, G9, G11 and P[6], P[13], P[23], and P[34]).
      There was no significant association between ARoV infection and clinical disease
      in pigs, suggesting that endemic asymptomatic circulation of ARoV may complicate
      rotavirus disease attribution during outbreaks of diarrhea in swine. Sequence
      analysis of the detected ARoVs suggested homology to recent human clinical cases
      and extensive genetic diversity. The epidemiological relevance of these findings
      for veterinary practitioners and to ongoing pediatric ARoV vaccine initiatives in
      Vietnam merits further study. 

PMID- 24679962
TI  - [Risk factors of serious bleeding among ambulatory patients taking antivitamin K
      aged 75 and over].
AB  - The benefits of anti-vitamin K (AVK) drugs have been acknowledged in several
      indications. Such indications increasing with increasing age, AVK prescriptions
      also increases with age. At the same time, conditions involving significant
      bleeding are common in this elderly population. It is thus essential to recognize
      the determining factors. This study included all patients taking AVK drugs aged
      75 years and older who sought emergency care at the Cochin Hospital from January
      to December 2011 for significant bleeding. These patients were compared with a
      cohort of patients aged 75 years or older who were taking AVK drugs and who were
      admitted to the same unit during the same time period for other reasons. The case
      control comparison included demographic data, comorbidity factors, multiple
      medications, emergency measured INR, and CHA2DS2VASC level. The hemorrhagic risk
      was evaluated by HEMORR2HAGES and HAS-BLED. A total of 34 patients were studied
      and compared with 70 case-controls. The Charlson comorbidity index was higher in
      patients than case-controls (P<0.05), with a much higher hemorrhagic risk for
      scores >= 9 (OR=2.5; P<0.05). Multiple medication was also more predominant in
      patients (P<0.05). The risk of serious hemorrhage was also higher when the
      hemorrhagic scores were high, especially for HEMORR2HAGES (P<0.0001) and HAS-BLED
      (P<0.001). The risk of serious hemorrhage in elderly outpatients taking AVK drugs
      is related to their higher comorbidity and hemorrhagic levels which need to be
      evaluated before starting or stopping AVK treatment.

PMID- 24679963
TI  - Seminars in Immunology. New vistas on NK cell development and function. Preface.

PMID- 24679964
TI  - Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry
      disease, novel GLA mutation and severe cardiac phenotype.
AB  - BACKGROUND AND OBJECTIVE: Fabry disease is an X-linked multisystemic lysosomal
      storage condition. We describe a large family with a novel GLA mutation:
      p.M187R/g7219 T>G. PATIENTS AND METHODS: Anamnesis/physical-exam, blood/urine
      analysis, alpha-Gal-A activity and/or genetic study of at-risk individuals and
      multidisciplinary evaluation in confirmed cases. RESULTS: 4 males and 13
      heterozygous-females displayed the mutation. Cardiac/renal/neurological disease
      was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in
      females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy.
      Delta wave suggestive of accessory pathway was identified in 1 male and 2
      females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2
      females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz
      Severity-Score-Index was severe for males and females over 40 years. 4/15(26%)
      developed early renal disease. 2 males needed dialysis. 1 male died at 69 years
      in spite of kidney-heart transplant. CONCLUSION: We describe the largest
      genetically confirmed Spanish family using multidisciplinary evaluation and MSSI
      calculation. The novel mutation p.M187R/g7219 T>G is associated with a
      particularly malignant cardiac phenotype in males and females over 40 years.
      Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with
      delta is being reported for the first time.

PMID- 24679965
TI  - Variation of thermal parameters in two different color morphs of a diurnal poison
      toad, Melanophryniscus rubriventris (Anura: Bufonidae).
AB  - We study the variation in thermal parameters in two contrasting populations
      Yungas Redbelly Toads (Melanophryniscus rubriventris) with different discrete
      color phenotypes comparing field body temperatures, critical thermal maximum and
      heating rates. We found significant differences in field body temperatures of the
      different morphs. Temperatures were higher in toads with a high extent of dorsal
      melanization. No variation was registered in operative temperatures between the
      study locations at the moment of capture and processing. Critical thermal maximum
      of toads was positively related with the extent of dorsal melanization.
      Furthermore, we founded significant differences in heating rates between morphs,
      where individuals with a high extent of dorsal melanization showed greater
      heating rates than toads with lower dorsal melanization. The color pattern
      thermal parameter relationship observed may influence the activity patterns and
      body size of individuals. Body temperature is a modulator of physiological and
      behavioral functions in amphibians, influencing daily and seasonal activity,
      locomotor performance, digestion rate and growth rate. It is possible that some
      growth constraints may arise due to the relationship of color pattern-metabolism
      allowing different morphs to attain similar sizes at different locations instead
      of body-size clines. 

PMID- 24679966
TI  - Thermal comfort of various building layouts with a proposed discomfort index
      range for tropical climate.
AB  - Recent years have seen issues related to thermal comfort gaining more momentum in
      tropical countries. The thermal adaptation and thermal comfort index play a
      significant role in evaluating the outdoor thermal comfort. In this study, the
      aim is to capture the thermal sensation of respondents at outdoor environment
      through questionnaire survey and to determine the discomfort index (DI) to
      measure the thermal discomfort level. The results indicated that most respondents
      had thermally accepted the existing environment conditions although they felt
      slightly warm and hot. A strong correlation between thermal sensation and
      measured DI was also identified. As a result, a new discomfort index range had
      been proposed in association with local climate and thermal sensation of
      occupants to evaluate thermal comfort. The results had proved that the
      respondents can adapt to a wider range of thermal conditions.Validation of the
      questionnaire data at Putrajaya was done to prove that the thermal sensation in
      both Putrajaya and UTM was almost similar since they are located in the same
      tropical climate region. Hence, a quantitative field study on building layouts
      was done to facilitate the outdoor human discomfort level based on newly proposed
      discomfort index range. The results showed that slightly shaded building layouts
      of type- A and B exhibited higher temperature and discomfort index. The resultant
      adaptive thermal comfort theory was incorporated into the field studies as well.
      Finally, the study also showed that the DI values were highly dependent on
      ambient temperature and relative humidity but had fewer effects for solar
      radiation intensity. 

PMID- 24679967
TI  - Combined effect of temperature and zinc on Caenorhabditis elegans wild type and
      daf-21 mutant strains.
AB  - Heavy metal pollution in aquatic ecosystems is a far reaching environmental
      problem. The possible influences of heavy metal exposure and the potential harm
      to organisms when combined with other environmental stressors such as temperature
      have been largely unexplored. An aquatic toxicity test of Caenorhabditis elegans
      was performed to estimate the 24h median lethal concentration (LC50) of different
      zinc concentrations at different temperatures (15 degrees C, 20 degrees C, 25
      degrees C, and 30 degrees C). We also examined the time course thermotolerance on
      wild type (N2) and daf-21 null (JT6130) adults exposed to 6.1mM zinc at 37
      degrees C. Hsp90 protein expression level in response to the combined effect of
      temperature and zinc toxicity was also investigated by both Western blots and
      ELISA. Our results show that C. elegans wild type nematodes exhibit severe lethal
      toxicity after a 24h exposure to zinc at higher temperatures. In addition, the
      expression level of Hsp90 was highly inhibited in adult worms subjected to zinc
      stress. This toxicity assay at different temperatures provides insight into
      organism response to combined effects of temperature and zinc toxicity. 

PMID- 24679968
TI  - The thermal tolerance of crayfish could be estimated from respiratory electron
      transport system activity.
AB  - Whether electron transport system (ETS) activity could be used as an estimator of
      crayfish thermal tolerance has been investigated experimentally. Food consumption
      rate, respiration rates in the air and water, the difference between energy
      consumption and respiration costs at a given temperature ('potential growth
      scope', PGS), and ETS activity of Orconectes limosus and Pacifastacus leniusculus
      were determined over a temperature range of 5-30 degrees C. All concerned
      parameters were found to be temperature dependent. The significant correlation
      between ETS activity and PGS indicates that they respond similarly to temperature
      change. The regression analysis of ETS activity as an estimator of thermal
      tolerance at the mitochondrial level and PGS as an indicator of thermal tolerance
      at the organismic level showed the shift of optimum temperature ranges of ETS
      activity to the right for 2 degrees  in O. limosus and for 3 degrees  in P.
      leniusculus. Thus, lower estimated temperature optima and temperatures of optimum
      ranges of PGS compared to ETS activity could indicate higher thermal sensitivity
      at the organismic level than at a lower level of complexity (i.e. at the
      mitochondrial level). The response of ETS activity to temperature change,
      especially at lower and higher temperatures, indicates differences in the
      characteristics of the ETSs in O. limosus and P. leniusculus. O. limosus is less
      sensitive to high temperature. The significant correlation between PGS and ETS
      activity supports our assumption that ETS activity could be used for the rapid
      estimation of thermal tolerance in crayfish species. 

PMID- 24679969
TI  - Temporal patterns of cardiac performance and genes encoding heat shock proteins
      and metabolic sensors of an intertidal limpet Cellana toreuma during sublethal
      heat stress.
AB  - Intertidal invertebrates develop effective physiological adaptations to cope with
      the rapidly changing thermal environment in the intertidal zone. In the present
      study, the temporal patterns of heart rate, protein carbonyl groups, and genes
      encoding heat shock proteins (hsp70 and hsp90) and metabolic sensors (ampkalpha,
      ampkbeta and sirt1) were measured to study the effect of sublethal heat stress on
      the cardiac function, oxidative stress, heat shock response and cellular
      metabolism of an intertidal limpet Cellana toreuma. All the physiological
      parameters are sensitive to temperature and duration of heat stress. Spearman
      correlation analysis revealed that the correlations between heart rate and levels
      of heat shock proteins mRNA and metabolic sensors mRNA were statistically
      significant. These results further suggest that cardiac function plays crucial
      roles in cellular energy metabolism and heat shock responses. The significant
      increase of protein carbonyl groups at 34 degrees C after 4h exposure indicated
      that the failure of cardiac function and the increase of anaerobic metabolism
      partly leads to the increase of protein carbonyl groups. Generally, the
      physiological responses to heat stress are sensitive to temperature and are
      energy-consumptive, as indicated by the upregulation of metabolic sensors mRNA.
      However, the upregulation of heat shock proteins and metabolic sensors at the
      post-transcriptional level and related functions need to be confirmed in further
      experiments. 

PMID- 24679970
TI  - Effect of temperature in multiple biomarkers of oxidative stress in coastal
      shrimp.
AB  - Various studies in captivity and in the wild have pointed to the effect of
      season, and temperature in particular, in the levels of the oxidative stress
      biomarkers currently used for environmental quality assessment. However,
      knowledge on how temperature affects the oxidative stress response is unavailable
      for most species. This study investigated the effect of increasing temperature on
      lipid peroxidation, catalase activity, superoxide dismutase and glutathione-S
      transferase in the shrimps, Palaemon elegans and Palaemon serratus. It was
      concluded that increasing temperatures significantly affect all the biomarkers
      tested in both species, with the exception of superoxide dismutase in P. serratus
      which was not affected by temperature. The oxidative stress response was more
      intense in P. elegans, than in P. serratus, producing higher peaks of all
      biomarkers at temperatures between 22 degrees C and 26 degrees C, followed by low
      levels at higher temperatures. It was concluded that monitoring of ecosystems
      using oxidative stress biomarkers should take into account the species and
      thermal history of the organisms. Sampling should be avoided during heat waves
      and immediately after heat waves. 

PMID- 24679971
TI  - Effect of simultaneous variation in temperature and ammonia concentration on
      percent fertilization and hatching in Crassostrea ariakensis.
AB  - The combined effects of temperature and ammonia concentration on the percent
      fertilization and percent hatching in Crassostrea ariakensis were examined under
      laboratory conditions using the central composite design and response surface
      methodology. The results indicated: (1) The linear effects of temperature and
      ammonia concentration on the percent fertilization were significant (P<0.05), and
      the quadratic effects were highly significant (P<0.01). The interactive effect
      between temperature and ammonia concentration on the percent fertilization was
      not significant (P>0.05). (2) The linear effect of temperature on the percent
      hatching was highly significant (P<0.01), and that of ammonia concentration was
      nonsignificant (P>0.05). The quadratic effects of temperature and ammonia
      concentration on the percent hatching were highly significant (P<0.01). The
      interaction on the percent hatching was not significant (P>0.05). Temperature was
      more important than ammonia in influencing the fertilization and hatching in C.
      ariakensis. (3) The model equations of the percent fertilization and hatching
      towards temperature and ammonia concentration were established, with the
      coefficients of determination R(2)=99.4% and 99.76%, respectively. Through the
      lack-of-fit test, these models were of great adequacy. The predictive
      coefficients of determination for the two model equations were as high as 94.6%
      and 98.03%, respectively, showing that they could be used for practical
      projection. (4) Via the statistical simultaneous optimization technique, the
      optimal factor level combination, i.e., 25 degrees C/0.038mgmL(-1), was derived,
      at which the greatest percent fertilization 95.25% and hatching 83.26% was
      achieved, with the desirability being 97.81%. Our results may provide
      advantageous guidelines for the successful reproduction of C. ariakensis. 

PMID- 24679972
TI  - Thermoregulation and microhabitat use in mountain butterflies of the genus
      Erebia: importance of fine-scale habitat heterogeneity.
AB  - Mountain butterflies have evolved efficient thermoregulation strategies enabling
      their survival in marginal conditions with short flight season and unstable
      weather. Understanding the importance of their behavioural thermoregulation by
      habitat use can provide novel information for predicting the fate of alpine
      Lepidoptera and other insects under ongoing climate change. We studied the link
      between microhabitat use and thermoregulation in adults of seven species of a
      butterfly genus Erebia co-occurring in the Austrian Alps. We captured individuals
      in the field and measured their body temperature in relation to microhabitat and
      air temperature. We asked whether closely related species regulate their body
      temperature differently, and if so, what is the effect of behaviour, species
      traits and individual traits on body to air and body to microhabitat temperature
      differences. Co-occurring species differed in mean body temperature. These
      differences were driven by active microhabitat selection by individuals and also
      by species-specific habitat preferences. Species inhabiting grasslands and rocks
      utilised warmer microclimates to maintain higher body temperature than woodland
      species. Under low air temperatures, species of rocky habitats heated up more
      effectively than species of grasslands and woodlands which allowed them to stay
      active in colder weather. Species morphology and individual traits play rather
      minor roles in the thermoregulatory differences; although large species and young
      individuals maintained higher body temperature. We conclude that diverse
      microhabitat conditions at small spatial scales probably contribute to sympatric
      occurrence of closely related species with different thermal demands and that
      preserving heterogeneous conditions in alpine landscapes might mitigate
      detrimental consequences of predicted climate change. 

PMID- 24679973
TI  - Effect of dietary supplementation of l-tryptophan on thermal tolerance and oxygen
      consumption rate in Cirrhinus mrigala fingerlings under varied stocking density.
AB  - A 60 day feeding trial was conducted to study the effect of dietary l-tryptophan
      on thermal tolerance and oxygen consumption rate of freshwater fish, mrigala,
      Cirrhinus mrigala reared under ambient temperature at low and high stocking
      density. Four hundred eighty fingerlings were distributed into eight experimental
      groups. Four groups each of low density group (10 fishes/75L water) and higher
      density group (30 fishes/75L water) were fed a diet containing 0, 0.68, 1.36 or
      2.72% l-tryptophan in the diet, thus forming eight experimental groups namely,
      Low density control (LC) (basal feed +0% l-tryptophan); LT1 (basal feed+0.68% l
      tryptophan); LT2 (basal feed+1.36% l-tryptophan); LT3 (basal feed+2.72% l
      tryptophan); high density control (HC) (basal feed+0% l-tryptophan); HT1 (basal
      feed+0.68% l-tryptophan); HT2 (basal feed+1.36% l-tryptophan); and HT3 (basal
      feed+2.72% l-tryptophan) were fed at 3% of the body weight. The test diets having
      crude protein 34.33+/-0.23 to 35.81+/-0.18% and lipid 423.49+/-1.76 to 425.85+/
      0.31KCal/100g were prepared using purified ingredients. The possible role of
      dietary l-tryptophan on thermal tolerance and oxygen consumption rate was
      assessed in terms of critical thermal maxima (CTMax), critical thermal minima
      (CTMin), lethal thermal maxima (LTMax) and lethal thermal minima (LTMin). The
      CTMax, CTMin, LTMax and LTMin values were found to be significantly higher
      (p<0.05) in the treatment groups with CTMax 42.94+/-0.037 (LT2); LT Max 43.18+/
      0.070 (LT2); CTMin 10.47+/-0.088 (LT2) and LTMin 9.42+/-0.062 (LT3), whereas the
      control group showed a lower tolerance level. The same trend was observed in the
      high density group (CTMax 42.09+/-0.066 (LT3); LTMax 43 23+/-0.067 (HT3); CTMin
      10.98+/-0.040 (HT3) and LTMin 9.74+/-0.037 (HT3). However, gradual
      supplementation of dietary l-tryptophan in the diet significantly reduced the
      oxygen consumption rate in both the low density group (Y=-26.74x+222.4, r2=0.915)
      and the high density group (Y=-32.96x+296.5, r2=0.8923). Dietary supplementation
      of l-tryptophan at a level of 1.36% improved the thermal tolerance level and
      reduced the oxygen consumption rate in C. mrigala fingerlings. 

PMID- 24679974
TI  - Behavioural thermoregulation and the relative roles of convection and radiation
      in a basking butterfly.
AB  - Poikilothermic animals are often reliant on behavioural thermoregulation to
      elevate core-body temperature above the temperature of their surroundings.
      Butterflies are able to do this by altering body posture and location while
      basking, however the specific mechanisms that achieve such regulation vary among
      species. The role of the wings has been particularly difficult to describe, with
      uncertainty surrounding whether they are positioned to reduce convective heat
      loss or to maximise heat gained through radiation. Characterisation of the extent
      to which these processes affect core-body temperature will provide insights into
      the way in which a species' thermal sensitivity and morphological traits have
      evolved. We conducted field and laboratory measurements to assess how basking
      posture affects the core-body temperature of an Australian butterfly, the common
      brown (Heteronympha merope). We show that, with wings held open, heat lost
      through convection is reduced while heat gained through radiation is
      simultaneously maximised. These responses have been incorporated into a
      biophysical model that accurately predicts the core-body temperature of basking
      specimens in the field, providing a powerful tool to explore how climate
      constrains the distribution and abundance of basking butterflies. 

PMID- 24679975
TI  - Repeated thermal stressor causes chronic elevation of baseline corticosterone and
      suppresses the physiological endocrine sensitivity to acute stressor in the cane
      toad (Rhinella marina).
AB  - Extreme environmental temperature could impact the physiology and ecology of
      animals. The stress endocrine axis provides necessary physiological stress
      response to acute (day-day) stressors. Presently, there are no empirical
      evidences showing that exposure to extreme thermal stressor could cause chronic
      stress in amphibians. This could also modulate the physiological endocrine
      sensitivity to acute stressors and have serious implications for stress coping in
      amphibians, particularly those living in fragmented and disease prone
      environments. We addressed this important question using the cane toad (Rhinella
      marina) model from its introduced range in Queensland, Australia. We quantified
      their physiological endocrine sensitivity to a standard acute (capture and
      handling) stressor after exposing the cane toads to thermal shock at 35 degrees C
      for 30min daily for 34 days. Corticosterone (CORT) responses to the capture and
      handling protocol were measured on three sampling intervals (days 14, 24, and 34)
      to determine whether the physiological endocrine sensitivity was maintained or
      modulated over-time. Two control groups (C1 for baseline CORT measurement only
      and C2 acute handled only) and two temperature treatment groups (T1 received
      daily thermal shock up to day 14 only and a recovery phase of 20 days and T2
      received thermal shock daily for 34 days). Results showed that baseline CORT
      levels remained high on day 14 (combined effect of capture, captivity and thermal
      stress) for both T1 and T2. Furthermore, baseline CORT levels decreased for T1
      once the thermal shock was removed after day 14 and returned to baseline by day
      29. On the contrary, baseline CORT levels kept on increasing for T2 over the 34
      days of daily thermal shocks. Furthermore, the magnitudes of the acute CORT
      responses or physiological endocrine sensitivity were consistently high for both
      C1 and T1. However, acute CORT responses for T2 toads were dramatically reduced
      between days 24 and 34. These novel findings suggest that repeated exposure to
      extreme thermal stressor could cause chronic stress and consequently suppress the
      physiological endocrine sensitivity to acute stressors (e.g. pathogenic diseases)
      in amphibians. 

PMID- 24679976
TI  - Temperature evolution in tissues embedded with large blood vessels during photo
      thermal heating.
AB  - During laser-assisted photo-thermal therapy, the temperature of the heated tissue
      region must rise to the therapeutic value (e.g., 43 degrees C) for complete
      ablation of the target cells. Large blood vessels (larger than 500 micron in
      diameter) at or near the irradiated tissues have a considerable impact on the
      transient temperature distribution in the tissue. In this study, the cooling
      effects of large blood vessels on temperature distribution in tissues during
      laser irradiation are predicted using finite element based simulation. A uniform
      flow is assumed at the entrance and three-dimensional conjugate heat transfer
      equations in the tissue region and the blood region are simultaneously solved for
      different vascular models. A volumetric heat source term based on Beer-Lambert
      law is introduced into the energy equation to account for laser heating. The
      heating pattern is taken to depend on the absorption and scattering coefficients
      of the tissue medium. Experiments are also conducted on tissue mimics in the
      presence and absence of simulated blood vessels to validate the numerical model.
      The coupled heat transfer between thermally significant blood vessels and their
      surrounding tissue for three different tissue-vascular networks are analyzed
      keeping the laser irradiation constant. A surface temperature map is obtained for
      different vascular models and for the bare tissue (without blood vessels). The
      transient temperature distribution is seen to differ according to the nature of
      the vascular network, blood vessel size, flow rate, laser spot size, laser power
      and tissue blood perfusion rate. The simulations suggest that the blood flow
      through large blood vessels in the vicinity of the photothermally heated tissue
      can lead to inefficient heating of the target. 

PMID- 24679977
TI  - Fitness costs associated with different frequencies and magnitudes of temperature
      change in the butterfly Bicyclus anynana.
AB  - Plastic responses to changes in environmental conditions are ubiquitous and
      typically highly effective, but are predicted to incur costs. We here investigate
      the effects of different frequencies and magnitudes of temperature change in the
      tropical butterfly Bicyclus anynana, considering developmental (Experiment 1) and
      adult stage plasticity (Experiment 2). We predicted negative effects of more
      frequent temperature changes on development, immune function and/or reproduction.
      Results from Experiment 1 showed that repeated temperature changes during
      development, if involving large amplitudes, negatively affect larval time, larval
      growth rate and pupal mass, while adult traits remained unaffected. However,
      results from treatment groups with smaller temperature amplitudes yielded no
      clear patterns. In Experiment 2 prolonged but not repeated exposure to 39 degrees
      C increased heat tolerance, potentially reflecting costs of repeatedly activating
      emergency responses. At the same time fecundity was more strongly reduced in the
      group with prolonged heat stress, suggesting a trade-off between heat tolerance
      and reproduction. Clear effects were restricted to conditions involving large
      temperature amplitudes or high temperatures. 

PMID- 24679978
TI  - Thermal energetics of the New-Guinean moss-forest rat (Rattus niobe) in
      comparison with other tropical murid rodents.
AB  - The thermal energetics of rodents from cool, wet tropical highlands are poorly
      known. Metabolic rate, body temperature and thermal conductance were measured in
      the moss-forest rat, Rattus niobe (Rodentia), a small murid endemic to the
      highlands of New Guinea. These data were evaluated in the context of the
      variation observed in the genus Rattus and among tropical murids. In 7 adult R.
      niobe, basal metabolic rate (BMR) averaged 53.6+/-6.6mLO2h(-1), or 103% of the
      value predicted for a body mass of 42.3+/-5.8g. Compared to other species of
      Rattus, R. niobe combines a low body temperature (35.5+/-0.6 degrees C) and a
      moderately low minimal wet thermal conductance cmin (5.88+/-0.7mLO2h(-1) degrees
      C(-1), 95% of predicted) with a small size, all of which lead to reduced energy
      expenditure in a constantly cool environment. The correlations of mean annual
      rainfall and temperature, altitude and body mass with BMR, body temperature and
      cmin were analyzed comparatively among tropical Muridae. Neither BMR, nor cmin or
      body temperature correlated with ambient temperature or altitude. Some of the
      factors which promote high BMR in higher latitude habitats, such as seasonal
      exposure to very low temperature and short reproductive season, are lacking in
      wet montane tropical forests. BMR increased with rainfall, confirming a pattern
      observed among other assemblages of mammals. This correlation was due to the low
      BMR of several desert adapted murids, while R. niobe and other species from wet
      habitats had a moderate BMR. 

PMID- 24679979
TI  - Effects of temperature on complexes I and II mediated respiration, ROS generation
      and oxidative stress status in isolated gill mitochondria of the mud crab Scylla
      serrata.
AB  - Effects of fluctuations in habitat temperature (18-30 degrees ) on mitochondrial
      respiratory behavior and oxidative metabolic responses in the euryhaline
      ectotherm Scylla serrata are not fully understood. In the present study, effects
      of different temperatures ranging from 12 to 40 degrees C on glutamate and
      succinate mediated mitochondrial respiration, respiratory control ratio (RCR),
      ATP generation rate, ratio for the utilization of phosphate molecules per atomic
      oxygen consumption (P/O), levels of lipid peroxidation and H2O2 in isolated gill
      mitochondria of S. serrata are reported. The pattern of variation in the studied
      parameters was similar for the two substrates at different temperatures. The
      values recorded for RCR (>=3) and P/O ratio (1.4-2.7) at the temperature range of
      15-25 degrees C were within the normal range reported for other animals (3-10 for
      RCR and 1.5-3 for P/O). Values for P/O ratio, ATP generation rate and RCR were
      highest at 18 degrees C when compared to the other assay temperatures. However,
      at low and high extreme temperatures, i.e. at 12 and 40 degrees C, states III and
      IV respiration rates were not clearly distinguishable from each other indicating
      that mitochondria were completely uncoupled. Positive correlations were noticed
      between temperature and the levels of both lipid peroxidation and H2O2. It is
      inferred that fluctuations on either side of ambient habitat temperature may
      adversely influence mitochondrial respiration and oxidative metabolism in S.
      serrata. The results provide baseline data to understand the impacts of acute
      changes in temperature on ectotherms inhabiting estuarine or marine environments.

PMID- 24679981
TI  - [Therapeutic education in primary cardiovascular prevention. Interests and
      limits].
AB  - GOAL OF THE STUDY: Lifestyle improvement is useful in the prevention of
      cardiovascular disease, but its practical implementation in the general
      population is limited. Patient therapeutic education can help go beyond these
      limits. PATIENTS AND METHODS: In primary prevention, we propose a personalized
      program including one or several individual and collective sessions to help the
      participants towards a healthier lifestyle. This includes better education about
      six risk factors (tobacco, sedentary lifestyle, overweight, high blood pressure,
      high cholesterol, diabetes) as well as advice on better eating habits. The first
      recommendation is to limit processed meats, the other recommendations advise more
      fish, green vegetables, whole grains and beans, and fruits. Scores are attributed
      to six risk factors and five eating habits. These scores are given at the time of
      the first session and again a year later, thus permitting time comparisons.
      RESULTS: For the first 291 participants in the program, we observed at one year a
      significant improvement in physical activities of endurance and in the
      consumption of the recommended food groups (fish, green vegetables, fruits, whole
      grains and beans). CONCLUSION: The patient's lifestyle has improved as a whole,
      certain parameters more than others. Assessed patient therapeutic education
      should be offered to a larger number of people.

PMID- 24679980
TI  - When is a child with status epilepticus likely to have Dravet syndrome?
AB  - PURPOSE: To identify clinical risk factors for Dravet syndrome (DS) in a
      population of children with status epilepticus (SE). MATERIAL AND METHODS:
      Children aged between 1 month and 16 years with at least one episode of SE were
      referred from 6 pediatric neurology centers in Switzerland. SE was defined as a
      clinical seizure lasting for more than 30min without recovery of normal
      consciousness. The diagnosis of DS was considered likely in previously healthy
      patients with seizures of multiple types starting before 1 year and developmental
      delay on follow-up. The presence of a SCN1A mutation was considered confirmatory
      for the diagnosis. Data such as gender, age at SE, SE clinical presentation and
      recurrence, additional seizure types and epilepsy diagnosis were collected. SCN1A
      analyses were performed in all patients, initially with High Resolution Melting
      Curve Analysis (HRMCA) and then by direct sequencing on selected samples with an
      abnormal HRMCA. Clinical and genetic findings were compared between children with
      DS and those with another diagnosis, and statistical methods were applied for
      significance analysis. RESULTS: 71 children with SE were included. Ten children
      had DS, and 61 had another diagnosis. SCN1A mutations were found in 12 of the 71
      patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy
      with Febrile Seizures+(GEFS+) context). The median age at first SE was 8 months
      in patients with DS, and 41 months in those with another epilepsy syndrome
      (p<0.001). Nine of the 10 DS patients had their initial SE before 18 months.
      Among the 26 patients aged 18 months or less at initial SE, the risk of DS was
      significantly increased for patients with two or more episodes (56.3%), as
      compared with those who had only one episode (0.0%) (p=0.005). CONCLUSION: In a
      population of children with SE, patients most likely to have DS are those who
      present their initial SE episode before 18 months, and who present with recurrent
      SE episodes.

PMID- 24679982
TI  - Blockade of Syk ameliorates the development of murine sclerodermatous chronic
      graft-versus-host disease.
AB  - BACKGROUND: Murine sclerodermatous chronic graft-versus-host disease (Scl-cGVHD)
      is a model for human Scl-cGVHD and systemic sclerosis (SSc). Syk is expressed in
      most of hematopoietic cells, fibroblasts, and endothelial cells. Syk is a protein
      tyrosine kinase that has an important role in transmitting signals from a variety
      of cell surface receptors. OBJECTIVE: This study aims to investigate the effect
      of R788 (fostamatinib sodium), an oral prodrug that is rapidly converted to a
      potent inhibitor of Syk, R406, on Scl-cGVHD. METHODS: R788 was orally
      administered twice a day to allogeneic recipients from day 14 to day 42 after
      bone marrow transplantation (BMT). In vitro, proliferation of GVHD-derived CD4(+)
      T cells and CD11b(+) cells was analyzed by R406. RESULTS: Allogeneic BMT
      increased Syk phosphorylation in T, B, and CD11b(+) cells. The administration of
      R788 attenuated severity and fibrosis of Scl-cGVHD. The elevated expressions of
      CXCR4 on T cells, B cells, and CD11b(+) cells were significantly down-regulated
      by R788 treatment. R788 reduced memory CD4(+) T cells (CD44(hi)CD62L(-)CD4(+)).
      R406 inhibited proliferation of GVHD CD4(+) T cells and CD11b(+) cells in vitro.
      In addition, R788 treatment, inhibited proliferation of CD11b(+) cells in Scl
      cGVHD mice. R788 treatment also reduced skin mRNA expressions of MCP-1, MIP
      1alpha, IFN-gamma, IL-13, IL-17A, and TGF-beta1, but not influenced RANTES,
      CXCL12, and TFN-alpha. CONCLUSION: Blockade of Syk suppressed migration factor of
      immune cells and antigen-specific memory CD4(+) T cells and proliferation and
      activation of GVHD CD4(+) T cells and CD11b(+) cells. The current studies
      suggested that Syk inhibitor is a potential candidate for use in treating
      patients with Scl-cGVHD and SSc.

PMID- 24679983
TI  - Comparison of visual acuity and higher-order aberrations after femtosecond
      lenticule extraction and small-incision lenticule extraction.
AB  - PURPOSE: To compare postoperative visual acuity and higher-order aberrations
      (HOAs) after femtosecond lenticule extraction (FLEX) and after small-incision
      lenticule extraction (SMILE). METHODS: Medical records of refractive lenticule
      extraction patients were retrospectively reviewed. Twenty patients were treated
      with FLEX. A comparable group of 20 SMILE patients were retrospectively
      identified. Only one eye of each patient was randomly chosen for the study.
      Visual acuity, subjective manifest refraction and corneal topography before and 6
      months after the surgery were analyzed for both groups. Total HOAs, spherical
      aberrations, coma and trefoil were calculated from topography data over the 4-
      and 6-mm-diameter central corneal zone. RESULTS: The mean preoperative SE was 
      4.03 +/- 1.61 in the SMILE group and -4.46 +/- 1.61 in the FLEX group. One year
      after surgery, the mean SE was -0.33 +/- 0.25 in the SMILE group and -0.31 +/-
      0.41 in the FLEX group (p=0.86). In the SMILE group a greater number of eyes were
      within +/-0.50D of the target refraction (95% versus 75%); however, the
      difference was not statistically significant (p=0.18). Furthermore, 80% of FLEX
      eyes and 95% of SMILE eyes had an uncorrected distance visual acuity of 20/25 or
      better (p=0.34). Total HOAs, spherical aberration, coma and trefoil increased
      postoperatively in both groups. However, there was no statistically significant
      difference between the groups preoperatively and postoperatively. CONCLUSION:
      FLEX and SMILE result in comparable refractive results. In addition, corneal
      aberrations induced by different techniques of lenticule extraction seemed
      similar to each other.

PMID- 24679984
TI  - Does increasing step width alter knee biomechanics in medial compartment knee
      osteoarthritis patients during stair descent?
AB  - BACKGROUND: Research shows that one of the first complaints from knee
      osteoarthritis (OA) patients is difficulty in stair ambulation due to knee pain.
      Increased step width (SW) has been shown to reduce first and second peak internal
      knee abduction moments, a surrogate variable for medial compartment knee joint
      loading, during stair descent in healthy older adults. This study investigates
      the effects of increased step width (SW) on knee biomechanics and knee pain in
      medial compartment knee OA patients during stair descent. METHODS: Thirteen
      medial compartment knee OA patients were recruited for the study. A motion
      analysis system was used to obtain three-dimensional joint kinematics. An
      instrumented staircase was used to collect ground reaction forces (GRF).
      Participants performed stair descent trials at their self-selected speed using
      preferred, wide, and wider SW. Participants rated their knee pain levels after
      each SW condition. RESULTS: Increased SW had no effect on peak knee abduction
      moments and knee pain. Patients reported low levels of knee pain during all stair
      descent trials. The 2nd peak knee adduction angle and frontal plane GRF at time
      of 2nd peak abduction moment were reduced with increasing SW. CONCLUSIONS: The
      findings suggest that increases in SW may not influence knee loads in medial
      compartment knee OA patients afflicted with low levels of knee pain during stair
      descent.

PMID- 24679985
TI  - Vertical and horizontal polymerization shrinkage in composite restorations.
AB  - OBJECTIVE: Polymerization shrinkage developed in vertical and horizontal
      directions after light activation of light-curing composite restorative
      materials. The purpose of this study was to examine the effects of vertical and
      horizontal polymerization shrinkage on: (a) dimensional changes of resin
      composites in tooth cavities; (b) shear bond strengths to enamel and dentin; and
      (c) marginal gap width in a non-reacting Teflon mold. METHODS: Vertical and
      horizontal polymerization shrinkage in tooth cavities were measured immediately
      (3 min) after light activation. With the same time lapse, shear bond strengths to
      enamel and dentin and marginal gap widths in Teflon mold were also measured.
      RESULTS: There was a significant correlation between vertical and horizontal
      polymerization shrinkage (r=0.647, p=0.043) in the tooth cavity. Composite
      materials which produced small vertical shrinkage also produced smaller
      horizontal shrinkage. Composite materials which produced small vertical shrinkage
      in the tooth cavity exhibited greater shear bond strengths to both enamel (r=
      0.697, p=0.025) and dentin (r=-0.752, p=0.012). Composite materials which
      produced smaller horizontal shrinkage produced smaller marginal gap widths in the
      Teflon mold (r=0.829, p=0.003). No relationships were observed between horizontal
      shrinkage in the tooth cavity and shear bond strengths to both enamel and dentin
      (p>0.05). SIGNIFICANCE: During the early stage of setting (<3 min) in tooth
      cavities, the vertical shrinkage of light-activated composite restorative
      materials was correlated with horizontal shrinkage.

PMID- 24679986
TI  - Type 3 diabetes mellitus. The revival of inhaled insulin?

PMID- 24679987
TI  - Why personality differences matter for social functioning and social structure.
AB  - We outline three main ways how personality differences can affect social
      functioning and social structure. By highlighting the broad and significant
      consequences that personality differences can have for social processes, our
      article might serve as a starting point for a research focus that aims at a
      systematic understanding of these consequences. 

PMID- 24679988
TI  - How to avoid misinterpreting lung function tests in children: a few practical
      tips.
AB  - Assessments of pulmonary function play an integral part in the clinical
      management of school age children as well as providing objective outcome measures
      in clinical and epidemiological research studies. Pulmonary function tests (PFTs)
      can also be undertaken in sleeping infants and in awake young children from 3
      years of age. However, the clinical utility of such assessments, which are
      generally confined to specialist centres, has yet to be established. Whether
      requesting or undertaking paediatric PFTs, or simply reading about how these
      tests have been applied in research studies, it is essential to question whether
      results have been interpreted in a meaningful way. This review summarises some of
      the issues that need to be considered, including: why the tests are being
      performed; which tests are most likely to detect the suspected pathophysiology;
      how often such tests should be repeated; whether results are likely to be
      reliable (in terms of data quality, repeatability and the availability of
      suitable reference equations with which to distinguish the effects of disease
      from those of growth and development), and whether the selected tests are likely
      to be feasible in the individual child or study group under investigation. 

PMID- 24679989
TI  - Resistive switching behavior in gelatin thin films for nonvolatile memory
      application.
AB  - This paper presents the characteristics of gelatin, which can cause reproducible
      resistive switching and bipolar resistive switching in aluminum (Al)/gelatin (35
      nm)/ITO devices. The memory devices exhibited a high ON/OFF ratio of over 10(6)
      and a long retention time of over 10(5) seconds. The resistive switching
      mechanism was investigated using the high-angle dark field transmission electron
      microscopy image of Al/gelatin/ITO devices in the pristine high-resistance state
      (HRS) and then in returning to HRS after the RESET process. The energy-dispersive
      X-ray spectroscopy analysis revealed the aggregation of N and Al elements and the
      simultaneous presence of carbon and oxygen elements in the rupture of filament
      paths. Furthermore, via a current-sensing atomic force microscopy, we found that
      conduction paths in the ON-state are distributed in a highly localized area,
      which is associated with a carbon-rich filamentary switching mechanism. These
      results support that the chelation of N binding with Al ions improves the
      conductivity of the low-resistance state but not the production of metal
      filaments. 

PMID- 24679990
TI  - Serotonin transporter gene hypomethylation predicts impaired antidepressant
      treatment response.
AB  - Variation in the serotonin transporter gene (5-HTT; SERT; SLC6A4) has been
      suggested to pharmacogenetically drive interindividual differences in
      antidepressant treatment response. In the present analysis, a 'pharmaco
      epigenetic' approach was applied by investigating the influence of DNA
      methylation patterns in the 5-HTT transcriptional control region on
      antidepressant treatment response. Ninety-four patients of Caucasian descent with
      major depressive disorder (MDD) (f = 61) were analysed for DNA methylation status
      at nine CpG sites in the 5-HTT transcriptional control region upstream of exon 1A
      via direct sequencing of sodium bisulfite treated DNA extracted from blood cells.
      Patients were also genotyped for the functional 5-HTTLPR/rs25531 polymorphisms.
      Clinical response to treatment with escitalopram was assessed by intra-individual
      changes of HAM-D-21 scores after 6 wk of treatment. Lower average 5-HTT
      methylation across all nine CpGs was found to be associated with impaired
      antidepressant treatment response after 6 wk (p = 0.005). This effect was
      particularly conferred by one individual 5-HTT CpG site (CpG2 (GRCh37 build,
      NC_000017.10 28.563.102; p = 0.002). 5-HTTLPR/rs25531 haplotype was neither
      associated with 5-HTT DNA methylation nor treatment response. This analysis
      suggests that DNA hypomethylation of the 5-HTT transcriptional control region -
      possibly via increased serotonin transporter expression and consecutively
      decreased serotonin availability - might impair antidepressant treatment response
      in Caucasian patients with MDD. This pharmaco-epigenetic approach could
      eventually aid in establishing epigenetic biomarkers of treatment response and
      thereby a more personalized treatment of MDD. 

PMID- 24679993
TI  - Smartphone data as objective measures of bipolar disorder symptoms.
AB  - The daily electronic self-monitoring Smartphone software "MONARCA" was used by 17
      patients with bipolar disorder for 3 consecutive months. Patients were rated
      fortnightly using Hamilton Depression rating Scale 17 items (HDRS-17) and Young
      Mania rating Scale (YMRS) (102 ratings) with blinding for Smartphone data.
      Objective Smartphone measures such as physical and social activity correlated
      with clinically rated depressive symptoms. Self-monitored depressive symptoms
      correlated significantly with HDRS-17 items score. 

PMID- 24679992
TI  - Context and explicit threat cue modulation of the startle reflex: preliminary
      evidence of distinctions between adolescents with principal fear disorders versus
      distress disorders.
AB  - Anxiety and depression are prevalent, impairing disorders. High comorbidity has
      raised questions about how to define and classify them. Structural models
      emphasise distinctions between "fear" and "distress" disorders while other
      initiatives propose they be defined by neurobiological indicators that cut across
      disorders. This study examined startle reflex (SR) modulation in adolescents with
      principal fear disorders (specific phobia; social phobia) (n=20), distress
      disorders (unipolar depressive disorders, dysthymia, generalised anxiety
      disorder; post-traumatic stress disorder) (n=9), and controls (n=29) during (a)
      baseline conditions, (b) threat context conditions (presence of contraction pads
      over the biceps muscle), and (c) an explicit threat cue paradigm involving phases
      that signalled safety from aversive stimuli (early and late stages of safe
      phases; early stages of danger phases) and phases that signalled immediate danger
      of an aversive stimulus (late stages of danger phases). Adolescents with
      principal fear disorders showed larger SRs than other groups throughout safe
      phases and early stages of danger phases. SRs did not differ between groups
      during late danger phases. Adolescents with principal distress disorders showed
      attenuated SRs during baseline and context conditions compared to other groups.
      Preliminary findings support initiatives to redefine emotional disorders based on
      neurobiological functioning. 

PMID- 24679994
TI  - Protective and risk factors for inpatient suicides: a nested case-control study.
AB  - This study aimed at estimating the protective effect of suicide precautions and
      clinical risk factors for inpatient suicides. A standardized precaution system
      was implemented in a large psychiatric center on January 1, 1996. A consecutive
      series of 33,121 admissions from 1998 to 2008 constituted the post-implementation
      cohort and 13,515 admissions from 1985 to 1995 constituted the pre-implementation
      cohort as comparison group. Inpatient suicides were identified via record linkage
      with national mortality database. For each of 41 inpatient suicides, four
      controls were randomly selected based on a nested case-control study. A
      standardized chart review process was employed to collate clinical information
      for each study subject. Risk and protective factors for inpatient suicides was
      estimated by conditional logistic regression. The findings showed that, among
      subjects with shorter lengths of stay, those admitted in post-implementation era
      had a significantly lower adjusted risk ratio (0.157, p=0.048) for inpatient
      suicides. Three depression-related symptoms elevated the risk for inpatient
      suicides: depressed mood (adjusted risk ratio=2.11, P=0.002), loss of energy
      (adjusted risk ratio=1.99, P=0.018), and psychomotor retardation (adjusted risk
      ratio=1.67, P=0.066; with marginal statistical significance). Suicide precautions
      have protective effect against inpatient suicides. A better assessment and
      prevention efforts is needed, particularly for those with depression-related
      symptoms. 

PMID- 24679995
TI  - Cocaine-induced psychotic symptoms in clinical setting.
AB  - Cocaine use is significantly associated with psychiatric co-morbidities of which
      psychotic symptoms are the most typical. The primary goal of this study is to
      estimate the life-time prevalence of cocaine-induced psychotic symptoms (CIPS) in
      a sample of patients without a history of primary psychosis, who attended
      specific out-patient drug-dependence treatment centres (ODDTCs). This is an
      observational, cross-sectional design and a consecutive sampling technique. The
      Scale for Assessment of Positive Symptoms-Cocaine Induced Psychosis (SAPS-CIP)
      was used to interview 114 patients who request treatment at specific ODDTCs for
      problems related to cocaine use. Most patients, 89.5% (95% CIs: 83.8-95.2%) had
      dependence of cocaine and 84.2% (95% CIs: 77.5-90.9%) showed at least one CIPS.
      Patients with CIPS had used cocaine more times throughout their lives and had a
      more frequency of use during the period of higher abuse severity in the last
      year, had higher severity of dependence score and had fewer abstinence periods
      greater than 30 days compared with those without CIPS. Cocaine dependency
      severity scale scores were significantly greater in patients with CIPS compared
      with those without CIPS. 

PMID- 24679996
TI  - Prefrontal grey and white matter neurometabolite changes after atomoxetine and
      methylphenidate in children with attention deficit/hyperactivity disorder: a (1)H
      magnetic resonance spectroscopy study.
AB  - Attention deficit/hyperactivity disorder (ADHD) is the most common
      neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits
      which are responsible for executive and attentional functions has been previously
      shown in ADHD. We investigated the neurometablite changes in areas included in
      dorsolateral prefrontal neural circuits after 2 months of long-acting
      methylphenidate or atomoxetine medication in children with ADHD who were
      responders to treatment. Twenty-one ADHD children were examined by single voxel
      (1)H-magnetic resonance spectroscopy (MRS) before and after 2 months of
      medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra
      were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter
      behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr
      (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr
      (choline/creatine) increased in the right DLPFC after atomoxetine medication.
      Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter
      after methylphenidate medication. We hypothesize that atomoxetine could decrease
      hyperactivation of DLPFC neurons and methylphenidate could lead to increased
      activation of cortical glutamatergic projections with the consequences of
      increased tonic dopamine release in the mesocortical system. 

PMID- 24679998
TI  - The evolution of skin pigmentation and hair texture in people of African
      ancestry.
AB  - Our species, Homo sapiens, evolved in Africa, and humanity's highest levels of
      genetic diversity are maintained there today. Underlying genetic diversity
      combined with the great range of solar regimes and climatic conditions found in
      Africa has contributed to a wide range of human integumentary phenotypes within
      the continent. Millions of Africans have moved, voluntarily and involuntarily, to
      other continents in the past 2000 years, and the range of integumentary
      phenotypes among admixed African diaspora populations is enormous. In this
      contribution, we do not catalog this variation, but provide basic evolutionary
      background as to how it developed in the first place. 

PMID- 24679997
TI  - Redefining the metabolic continuity of chloroplasts and ER.
AB  - As a hub for plant metabolism, plastids extensively exchange metabolites with the
      extraplastid environment. For polar metabolites, membrane transporters mediate
      this exchange, but for many plastid-synthesized nonpolar compounds, such
      transporters remain elusive. Here, we discuss recent data from transorganellar
      complementation studies that demonstrate that enzymes in one organelle can
      directly access nonpolar metabolites from a companion organelle. We propose that
      a mechanism, based on hemifused-membranes at plastid-endoplasmic reticulum (ER)
      contact sites, facilitates interorganellar interactions and allows enzymes
      direct, transporter-independent access to a range of nonpolar compounds in both
      organelle membranes. In a wider context, interorganellar metabolism at hemifusion
      interfaces would allow evolution of membrane-spanning pathways for the many
      thousands of nonpolar metabolites in the plant kingdom to be uncoupled from
      coevolution with nonpolar metabolite transporters. 

PMID- 24679999
TI  - What's new in objective assessment and treatment of facial hyperpigmentation?
AB  - Facial hyperpigmentation is common and challenging to treat in darker-skinned
      populations. A Medline literature search of articles published up to October 2013
      reporting the objective assessment of and/or treatment for melasma,
      postinflammatory hyperpigmentation, dermatosis papulosa nigra, lichen planus
      pigmentosus, and erythema dyschromicum perstans was reviewed. Objective
      assessment was only reported for melasma and postinflammatory hyperpigmentation.
      Furthermore, randomized controlled trial evidence was only reported for melasma.
      Although progress has been made, there is a need to develop more objective
      outcome measures and effective treatments for hyperpigmentation. 

PMID- 24680000
TI  - Cosmeceuticals: efficacy and influence on skin tone.
AB  - Cosmeceuticals are understood to be active cosmetics that are sold over-the
      counter, but have profound effects on skin appearance and functioning. This term
      has no legal meaning in the United States, because only cosmetics and
      pharmaceuticals are recognized by regulatory bodies. Cosmeceuticals are carefully
      developed and tested by the cosmetics industry to deliver consumer-recognizable
      benefits, with an excellent safety profile. Persons use these products worldwide,
      including those of African descent, for improvement of skin tone. This article
      discusses the issues surrounding cosmeceutical use by persons of African descent.

PMID- 24680001
TI  - A systematic approach to Afro-textured hair disorders: dermatoscopy and when to
      biopsy.
AB  - Trichoscopy facilitates the diagnosis of various hair and scalp disorders and is
      often useful in predicting the disease course. However, to date, few studies
      describe the dermoscopic findings unique to Afro-textured hair. This article
      reviews what is currently known regarding trichoscopy and discusses its
      usefulness in this population. 

PMID- 24680002
TI  - Traction alopecia: how to translate study data for public education--closing the
      KAP gap?
AB  - Traction alopecia (TA) affects up to 32% of women and 22% of high school girls
      with Afro-textured hair but can start in the preschool years. Traction induces
      inflammation and follicle damage. The risk of TA increases with symptomatic
      traction and combined hairstyles. To influence the practice of hairdressers and
      at risk individuals and help narrow the knowledge, attitudes, and practices (KAP)
      gap, scientific data should be translated into simple messages like "tolerate
      pain from a hairstyle and risk hair loss" and "no braids or weaves on relaxed
      hair". With appropriate education and public awareness, TA could potentially be
      eradicated. 

PMID- 24680003
TI  - Advances and challenges in hair restoration of curly Afrocentric hair.
AB  - Although the biochemical composition of hair is similar among racial and ethnic
      groups, the hair structure between them varies, and individuals with curly hair
      pose specific challenges and special considerations when a surgical option for
      alopecia is considered. Hair restoration in this population should therefore be
      approached with knowledge on the clinical characteristics of curly hair, hair
      grooming techniques that may influence the management, unique indications for the
      procedure, surgical instrumentation used, and the complications that may arise. 

PMID- 24680004
TI  - Central centrifugal cicatricial alopecia: what has been achieved, current clues
      for future research.
AB  - Central centrifugal cicatricial alopecia is an inflammatory type of central scalp
      hair loss seen primarily in women of African descent. The prevalence is unknown,
      but may vary from 2.7% to 5.7% and increases with age. This review outlines the
      history and current beliefs and identifies clues for future research for this
      enigmatic condition. Despite that the cause of central centrifugal cicatricial
      alopecia is unknown, research is ongoing. The role of cytokeratins, androgens,
      genetics, and various possible sources of chronic inflammation in disease
      pathogenesis remain to be elucidated. 

PMID- 24680005
TI  - Folliculitis keloidalis nuchae and pseudofolliculitis barbae: are prevention and
      effective treatment within reach?
AB  - Pseudofolliculitis barbae and folliculitis keloidalis nuchae are chronic
      follicular disorders disproportionately affecting men of African ancestry. This
      article explores the etiology, pathogenesis, treatment, and prevention strategies
      of these conditions. Effective treatment and prevention of these disorders
      involves pharmacologic and procedural interventions as well as behavioral
      modifications. 

PMID- 24680006
TI  - New insights on keloids, hypertrophic scars, and striae.
AB  - This article presents an overview of the literature regarding treatments for
      keloid disease, hypertrophic scars, and striae distensae in dark pigmented skin.
      Striae, keloid, and hypertrophic scarring present a challenging problem for both
      the clinician and patient. No single therapy is advocated for hypertrophic scars,
      keloid scars, or striae distensae. New therapies have shown promise in the
      treatment of hypertrophic and keloid scars, and in patients with dark pigmented
      skin. This article provides guidance on the assessment and determination of
      patients' suitability for certain treatment options, as well as advice on the
      follow-up of patients affected with problematic scarring and striae. 

PMID- 24680007
TI  - The spectrum of HIV-associated infective and inflammatory dermatoses in pigmented
      skin.
AB  - HIV and AIDS patients often suffer from various skin infections of viral,
      bacterial, and fungal origin. In addition, parasitic infestations are prevalent.
      Common inflammatory dermatoses include seborrheic dermatitis, psoriasis,
      photodermatitis, and pruritic papular eruptions. This article discusses some of
      these conditions with an emphasis on clinical presentation. In patients with
      pigmented skin, diagnosis maybe challenging and complicated by dyspigmentation. 

PMID- 24680008
TI  - Clinical presentations of severe cutaneous drug reactions in HIV-infected
      Africans.
AB  - Sub-Saharan Africa is the epicenter of the HIV pandemic and HIV-infected people
      are more susceptible to inflammatory dermatoses, infections, and drug eruptions.
      Many of the drugs used for HIV-associated opportunistic infections are associated
      with a higher incidence of drug-related toxicities and drug interactions. This
      article discusses the epidemiology, pharmacogenetics, and clinical features of
      idiosyncratic drug reactions in HIV-infected Africans. Special considerations in
      this population, including immune reconstitution inflammatory syndrome, multiple
      drug hypersensitivity syndrome, drug reactions in pregnancy, drug rechallenge in
      lichenoid drug eruptions, and anxiety/depression after cutaneous adverse drug
      reactions, are also briefly discussed. 

PMID- 24680009
TI  - Infective dermatitis associated with HTLV-1 mimics common eczemas in children and
      may be a prelude to severe systemic diseases.
AB  - Infective dermatitis associated with human T-cell lymphotropic virus type 1 (HTLV
      1) (IDH) is a chronic dermatitis that has been observed in a variable proportion
      of HTLV-1-infected children. IDH may serve as an early clinical marker for HTLV-1
      infection and an indicator of increased risk for developing other HTLV-1
      associated conditions. Factors that lead only some infected children to develop
      IDH are poorly understood. The variable clinical presentation of IDH, in
      particular its chronicity, the morphology and distribution of the lesions, and
      its clinical resemblance to other cutaneous inflammatory conditions, make it
      necessary to distinguish it from other common dermatoses. 

PMID- 24680010
TI  - Beyond "ethnicity" in dermatology.

PMID- 24680011
TI  - Phantom organ pain syndrome, a ghostly visitor to the ED.

PMID- 24680012
TI  - An uncommon cause of alteration of consciousness in a patient with systemic lupus
      erythematosus.

PMID- 24680013
TI  - Venezuela: violence, human rights, and health-care realities.

PMID- 24680014
TI  - Breastfeeding, early nutrition, and adult body fat.
AB  - OBJECTIVE: To examine the association between breastfeeding and adult body
      fatness, adjusting for nutritional intake in early childhood. STUDY DESIGN:
      Nutritional intakes of 73 healthy infants born in 1984 who participated in the 2
      decade-long Longitudinal Study of Nutrition and Growth in Children (Etude
      Longitudinale Alimentation Nutrition Croissance des Enfants [ELANCE]) were
      estimated at age 10 months and again at age 2 years. Breastfeeding was defined as
      any breastfeeding, including partial breastfeeding, regardless of duration. At
      age 20 years, weight, height, subscapular skinfold thickness (SF), and fat mass
      (assessed via bioelectrical impedance analysis) were measured. RESULTS: In this
      sample, 64% of the children had been breastfed. In linear regression models
      adjusted for mother's body mass index and father's profession, breastfeeding was
      not associated with any of the body fat measurements at 20 years (all P > .05).
      After adding nutritional intake variables (total energy and % energy from
      nutrients) to the models, breastfeeding became significantly associated with
      lower SF at 20 years. In particular, breastfed subjects had significantly lower %
      SF at 20 years after adjustment for energy and % fat intakes at 2 years of age,
      (beta = -28.25% SF; 95% CI, -50.28% to -6.21%; P = .013) or when adjusting for
      energy and % carbohydrates at 2 years of age (beta = -28.27% SF; 95% CI, -50.64%
      to -5.90%; P = .014). CONCLUSION: Breastfeeding was not associated with adult
      body fatness taking into account the usual confounding factors. However, after
      also adjusting for nutritional intake covariates, a protective effect of
      breastfeeding emerged. Early nutrition needs to be taken into account when
      examining the long-term health effects of breastfeeding.

PMID- 24680017
TI  - Long-term stability of implant-anchored orthodontics in an adult patient with a
      Class II Division 2 malocclusion and a unilateral molar scissors-bite.
AB  - This article reports the successful treatment using miniscrew anchorage of an
      adult patient with a severe deep overbite and a unilateral scissors-bite. A 23
      year-old woman had chief complaints of maxillary incisal crowding and difficulty
      chewing. She was diagnosed with a severe Class II Division 2 malocclusion with
      anterior crowding and a unilateral scissors-bite caused by buccal elongation of
      the maxillary left second molar. The maxillary first premolars were extracted,
      and 3 miniscrews were implanted as skeletal anchorage to resolve the functional
      and esthetic problems. The total active treatment period was 41 months. As a
      result of the implant-anchored orthodontic treatment, both the patient's facial
      profile and occlusion significantly improved. The asymmetric movements of the
      incisor paths and bilateral condyles during lateral excursions disappeared. The
      satisfactory facial profile and resultant occlusion were maintained throughout a
      49-month retention period. The patient was satisfied with the treatment results. 

PMID- 24680018
TI  - Surgically facilitated orthodontic treatment.

PMID- 24680016
TI  - Gland-preserving robotic surgery for benign submandibular gland tumours: a
      comparison between robotic and open techniques.
AB  - Benign tumours of the submandibular gland are usually treated surgically. Gland
      preserving techniques, which can be used to completely remove the tumour,
      preserve the function of the gland and reduce complications, but conventional
      open operations result in obvious scars on the neck. We aimed to investigate the
      feasibility and efficacy of gland-preserving robotic surgery using a hairline
      approach. We compared robotic with open techniques for gland-preserving
      operations to remove benign tumours of the submandibular gland. Patients were
      matched for age and sex (4 in each group). All patients in the robotic surgery
      group had their tumours removed successfully through hairline approaches. No
      patient had operative complications or postoperative functional nerve deficit,
      and an aesthetically pleasing outcome was achieved by concealing the scars within
      the hairline. Robotic operations took longer than open operations. No recurrence
      was noted during follow-up. Gland-preserving robotic surgery is a feasible
      alternative to conventional techniques and has potential advantages for safety
      and aesthetic outcome. 

PMID- 24680015
TI  - Traffic-related air pollution and asthma hospital readmission in children: a
      longitudinal cohort study.
AB  - OBJECTIVE: To examine the association between exposure to traffic-related air
      pollution (TRAP) and hospital readmission for asthma or bronchodilator-responsive
      wheezing. STUDY DESIGN: A population-based cohort of 758 children aged 1-16 years
      admitted for asthma or bronchodilator-responsive wheezing was assessed for asthma
      readmission within 12 months. TRAP exposure was estimated with a land use
      regression model using the home address at index admission, with TRAP
      dichotomized at the sample median (0.37 MUg/m3). Covariates included allergen
      specific IgE, tobacco smoke exposure, and social factors obtained at enrollment.
      Associations between TRAP exposure and readmission were assessed using logistic
      regression and Cox proportional hazards models. RESULTS: The study cohort was 58%
      African American and 32% white; 19% of the patients were readmitted within 12
      months of the original admission. Higher TRAP exposure was associated with a
      higher readmission rate (21% vs. 16%; P = .05); this association was not
      significant after adjusting for covariates (aOR, 1.4; 95% CI, 0.9-2.2). Race
      modified the observed association; white children with high TRAP exposure had 3
      fold higher odds of asthma readmission (OR, 3.0; 95% CI, 1.1-8.1), compared with
      white children with low TRAP exposure. In African American children, TRAP
      exposure was not associated with increased readmission (OR, 1.1; 95% CI, 0.6
      1.8). In children with high TRAP exposure, TRAP exposure was associated with
      decreased time to readmission in white children (hazard ratio, 3.2; 95% CI, 1.5
      6.7) compared with African American children (hazard ratio, 1.0; 95% CI, 0.7
      1.4). African American children had a higher readmission rate overall.
      CONCLUSION: TRAP exposure is associated with increased odds of hospital
      readmission in white children, but not in African American children.

PMID- 24680019
TI  - Orthodontic treatment combined with tooth transplantation for an adult patient
      with a missing mandibular first molar: long-term follow-up.
AB  - A Japanese woman, age 29 years 8 months, had a missing mandibular left first
      molar, bimaxillary dentoalveolar protrusion, and crowding. She had a skeletal
      Class II relationship and a long face with a steep mandible. She had previously
      undergone root canal treatment for the mandibular right second premolar, and the
      mandibular left third molar was impacted. The maxillary left first premolar was
      extracted for autotransplantation to the mandibular left first molar region.
      After confirmation of a favorable prognosis for the transplanted tooth, the
      maxillary right first premolar, the mandibular right second premolar, and the
      impacted mandibular left third molar were extracted for orthodontic treatment.
      The active orthodontic treatment period was 32 months. The patient returned for
      follow-up records 12 years 7 months after the active treatment, and her facial
      profile and occlusion were well maintained. At 13 years 9 months after
      transplantation, no abnormalities were observed with the transplanted tooth in
      the radiographic and clinical evaluations. 

PMID- 24680020
TI  - Ethics in orthodontics. Her trust is in your hands.

PMID- 24680021
TI  - Severe skeletal Class III malocclusion treated with 2-stage orthognathic surgery
      with a mandibular step osteotomy.
AB  - To reduce a large amount of mandibular setback and to prevent pharyngeal airway
      space narrowing when correcting a severe anteroposterior skeletal discrepancy, a
      mandibular step osteotomy is often combined with 2-stage orthognathic surgery.
      This case report describes a successful 2-stage orthognathic treatment combined
      with a mandibular step osteotomy. A 20-year-old man had severe mandibular
      protrusion, facial asymmetry, and macroglossia. Phase 1 surgery included the
      mandibular step osteotomy and a partial glossectomy; then we performed phase 2
      surgery with a 2-piece LeFort I segmental osteotomy and a bilateral intraoral
      vertical ramus osteotomy to correct the patient's mandibular protrusion and
      facial asymmetry. The total treatment period was 30 months, and the final result
      was improvement of the patient's facial appearance. 

PMID- 24680022
TI  - Interdisciplinary treatment of a nonsyndromic oligodontia patient with implant
      anchored orthodontics.
AB  - We successfully treated a nonsyndromic oligodontia patient with implant-anchored
      orthodontics and prosthetic restorations. A woman, age 18 years 11 months, had a
      straight profile and a skeletal Class I jaw-base relationship but had spaced
      arches because of 7 congenitally missing teeth. After leveling and alignment of
      the dentition, a titanium miniscrew was temporarily placed at the distal alveolus
      of the mandibular right first premolar, and the posterior teeth were mesialized
      to reduce the restorative spaces. After determination of the incisor positions, 3
      dental implants were respectively inserted at the sites of the maxillary canines
      and the mandibular left lateral incisor with guided bone regeneration procedures.
      Then, screw-retained temporary prostheses were delivered after subepithelial
      connective tissue grafting and used for molar mesialization as absolute
      anchorage. After 36 months of active orthodontic treatment, an acceptable
      occlusion was achieved, both functionally and esthetically, with the 3 dental
      implants. The maxillary and mandibular molars were mesialized, but the changes of
      incisor position were minimal. As a result, a proper facial profile was
      maintained, and an attractive smile was achieved. The resultant occlusion was
      stable throughout a 3-year retention period. In conclusion, interdisciplinary
      treatment combined with orthodontics, implant surgery, and prosthodontics was
      useful for a nonsyndromic oligodontia patient. Especially, the new strategy
      implant-anchored orthodontics-can facilitate the treatment more simply with
      greater predictability. 

PMID- 24680023
TI  - Litigation and legislation. Accelerated orthodontics or accelerated liability?

PMID- 24680024
TI  - Initial orthodontic alignment effectiveness with self-ligating and conventional
      appliances: a network meta-analysis in practice.
AB  - Systematic reviews of well-designed trials constitute a high level of scientific
      evidence and are important for medical decision making. Meta-analysis facilitates
      integration of the evidence using a transparent and systematic approach, leading
      to a broader interpretation of treatment effectiveness and safety than can be
      attained from individual studies. Traditional meta-analyses are limited to
      comparing just 2 interventions concurrently and cannot combine evidence
      concerning multiple treatments. A relatively recent extension of the traditional
      meta-analytical approach is network meta-analysis, which allows, under certain
      assumptions, the quantitative synthesis of all evidence under a unified framework
      and across a network of all eligible trials. Network meta-analysis combines
      evidence from direct and indirect information via common comparators;
      interventions can therefore be ranked in terms of the analyzed outcome. In this
      article, the network meta-analysis approach is introduced in a nontechnical
      manner using a worked example on the treatment effectiveness of conventional and
      self-ligating appliances. 

PMID- 24680025
TI  - Surgically facilitated orthodontic treatment: a systematic review.
AB  - INTRODUCTION: Corticotomy and dental distraction have been proposed as effective
      and safe methods to shorten orthodontic treatment duration in adolescent and
      adult patients. A systematic review was performed to evaluate the evidence
      supporting these claims. METHODS: PubMed, Embase, and Cochrane databases were
      searched until April 2013 for randomized controlled trials, controlled clinical
      trials, and case series with 5 or more subjects that focused on velocity of tooth
      movement, reduction of treatment duration, or complications with various surgical
      protocols. There were no language restrictions during the search phase.
      Publications were systematically assessed for eligibility, and 2 observers graded
      the methodologic quality of the included studies with a predefined scoring
      system. RESULTS: Eighteen articles met the inclusion criteria. Seven studies were
      clinical trials, with small investigated groups. Only studies of moderate and low
      values of evidence were found. Surgically facilitated treatment was indicated for
      various clinical problems. All publications reported temporarily accelerated
      tooth movement after surgery. No deleterious effects on the periodontium, no
      vitality loss, and no severe root resorption were found in any studies. However,
      the level of evidence to support these findings is limited owing to shortcomings
      in research methodologies and small treated groups. No research concerning long
      term stability could be included. CONCLUSIONS: Evidence based on the currently
      available studies of low-to-moderate quality showed that surgically facilitated
      orthodontics seems to be safe for the oral tissues and is characterized by a
      temporary phase of accelerated tooth movement. This can effectively shorten the
      duration of orthodontic treatment. However, to date, no prospective studies have
      compared overall treatment time and treatment outcome with those of a control
      group. Well-conducted, prospective research is still needed to draw valid
      conclusions.

PMID- 24680026
TI  - Patients', parents', and orthodontists' perceptions of the need for and costs of
      additional procedures to reduce treatment time.
AB  - INTRODUCTION: The purpose of this study was to evaluate patients', parents', and
      orthodontists' perspectives on orthodontic treatment duration and techniques for
      accelerating the rate of tooth movement. METHODS: Adolescent patients (n = 200)
      and their parents (n = 200), and adult patients (n = 50) from a multidoctor
      practice were personally surveyed regarding treatment duration and acceptance of
      appliances and techniques to enhance the speed of orthodontic treatment, and how
      much increase in fees they were willing to pay for these. Members of the American
      Association of Orthodontists were surveyed electronically regarding their
      willingness to use these techniques and appliances and the costs they were
      willing to pay for them. RESULTS: A total of 683 orthodontists replied to the
      electronic survey (7.5%). Approximately 70% of the orthodontists who replied to
      the survey were interested in adopting additional clinical procedures to reduce
      treatment time. No significant association was found between practice
      characteristics and interest in adopting clinical procedures to reduce treatment
      time. The invasiveness of the procedure was inversely related to its acceptance
      in all groups surveyed. Most orthodontists are willing to pay only up to 20% of
      their treatment fee to companies for the use of technologies that reduce
      treatment time, and most patients and parents were willing to pay only up to a
      20% increase in fees for these approaches. Orthodontists thought that increases
      in the rate of tooth movement could pose a problem for fee collection.
      CONCLUSIONS: Orthodontists and patients alike are interested in techniques that
      can accelerate tooth movement. Similarities between all groups were found
      regarding the acceptance of different approaches to accelerate tooth movement and
      the percentage of the orthodontic fee that would be paid for these techniques.
      Less-invasive techniques had greater acceptability in all groups.

PMID- 24680027
TI  - Effects of mechanical stress and growth on the velocity of tooth movement.
AB  - INTRODUCTION: In this study, we investigated the effects of the magnitudes of
      applied stress and growth status on the speed of tooth movement. METHODS: Eighty
      two maxillary canines in 41 subjects were retracted for 84 days by estimated
      stresses of 4, 13, 26, 52, or 78 kPa applied continuously via segmental
      mechanics. Dental impressions made at intervals of 1 to 14 days resulted in 9 or
      10 dental casts per subject. Three-dimensional tooth movements were quantified
      using these casts, custom reference templates, and a measuring microscope. Serial
      height and cephalometric measurements determined growth status. RESULTS: Distal
      tooth movement was linear with no lag phase in 96% of the teeth. Speeds averaged
      0.028, 0.040, 0.050, 0.054, and 0.061 mm per day (standard errors, +/- 0.004) for
      4, 13, 26, 52, and 78 kPa, respectively. The maximum difference in speed between
      teeth was 9:1. Teeth moved significantly faster (P <0.0001) in growing compared
      with nongrowing subjects, on average by 1.6-fold. Stress and speed of tooth
      movement were logarithmically related in growing (R(2) = 0.47) and nongrowing
      (R(2) = 0.34) subjects. Other tooth movements were relatively small, except for
      the distopalatal rotation of teeth moved by 78 kPa that averaged more than 19
      degrees . CONCLUSIONS: The speed of retraction was logarithmically related to the
      applied stress and was significantly faster in actively growing subjects compared
      with those who were not growing.

PMID- 24680028
TI  - Variables affecting orthodontic tooth movement with clear aligners.
AB  - INTRODUCTION: In this study, we examined the impacts of age, sex, root length,
      bone levels, and bone quality on orthodontic tooth movement. METHODS: Clear
      aligners were programmed to move 1 central incisor 1 mm over the course of 8
      weeks. Thirty subjects, ages 19 to 64, were enrolled, and measurements were made
      on digital models (percentage of tooth movement goal achieved). Morphometric
      features and bone quality were assessed with cone-beam computed tomography. Data
      from this study were combined with data from 2 similar studies to increase the
      power for some analyses. RESULTS: The mean percentage of tooth movement goal
      achieved was 57% overall. Linear regression modeling indicated a cubic
      relationship between age and tooth movement, with a decreasing rate of movement
      from ages 18 to 35 years, a slightly increasing rate from ages 35 to 50, and a
      decreasing rate from ages 50 to 70. The final decreasing trend was not apparent
      for women. As would be expected, the correlation was significant between the
      percentage of the goal achieved and the cone-beam computed tomography
      superimposed linear measures of tooth movement. A significant negative
      correlation was found between tooth movement and the measurement apex to the
      center of rotation, but bone quality, as measured by fractal dimension, was not
      correlated with movement. CONCLUSIONS: The relationship between age and tooth
      movement is complex and might differ for male and female patients. Limited
      correlations with cone-beam computed tomography morphology and rate of tooth
      movement were detected.

PMID- 24680029
TI  - How does the amount of surgical insult affect bone around moving teeth?
AB  - INTRODUCTION: The purpose of this study was to determine how the amount of
      surgical insult affects the quantity and maturity of dentoalveolar bone around
      teeth that have been orthodontically moved. METHODS: A split-mouth design with 8
      foxhound dogs was used to evaluate bone surrounding maxillary second premolars
      that were protracted for 15 days and retained for 7 weeks. The maxillary first
      premolars were extracted, and the interseptal bone was removed to within 1 mm of
      the second premolars; on the insult (lesser surgical insult) side, buccal and
      lingual vertical grooves were made in the extraction socket to undermine the
      mesial root of the second premolar; the insult+ (greater surgical insult) side
      was flapped and had modified corticotomies extending to, but not through, the
      lingual cortex 1 mm distal to the distal root, and 3 to 5 mm apical to both
      roots. Microcomputed tomography analyses were used to evaluate the material
      density, bone volume fraction, and trabecular characteristics of surrounding
      bone. Hematoxylin and eosin sections were used to determine osteoclast numbers,
      bone surface areas, and bone volumes. RESULTS: After 7 weeks of consolidation,
      there was significantly (P <0.05) less bone on the insult+ side; it was less
      dense and less mature than the bone on the insult side. Relative to the control
      bone, bone on the insult+ side was significantly less dense but showed no
      differences in bone volume. Preliminary histologic evaluations indicated
      increased numbers of osteoclasts and greater bone surface areas on the insult+
      side than the insult side, but no differences in bone volume. CONCLUSIONS:
      Increased surgical insults produce less dense and less mature bone but have no
      effect on bone volume at 9 weeks after surgery.

PMID- 24680030
TI  - Association of GRM3 polymorphism with white matter integrity in schizophrenia.
AB  - BACKGROUND: While the functional disconnectivity hypothesis of schizophrenia has
      received considerable attention, fewer studies have investigated the contribution
      of genotype to structural connectivity between brain regions either in
      schizophrenia patients or in healthy controls. In this study, we obtained
      diffusion tensor imaging (DTI) data and genome-wide single nucleotide
      polymorphism (SNP) data from 74 cases and 87 age- and gender-matched controls.
      METHODS: We used independent component analysis (ICA) to analyze fractional
      anisotropy (FA) values and correlated FA values with 121 SNPs in genes associated
      with myelination and/or schizophrenia risk. RESULTS: Using ICA, we identified 6
      maximally independent components in which the majority of the voxels corresponded
      to known white matter (WM) tracts. Among these WM-enriched components, two had FA
      values that were significantly decreased in patients. In addition, we examined
      the relationship between FA values and genotype and found that a SNP located in
      the intronic region of the metabotropic glutamate receptor 3 gene, GRM3, shows a
      significant correlation with FA values in a component containing tracts from the
      cortico-cerebellar-thalamic-cortical circuit of patients but not controls.
      CONCLUSIONS: Our findings strengthen the evidence for an association between GRM3
      genotype and schizophrenia and suggest a role for glutamate neurotransmission in
      the establishment and maintenance of myelinated fibers.

PMID- 24680031
TI  - Incomplete penetrance of NRXN1 deletions in families with schizophrenia.
AB  - Neurexin 1 (NRXN1) is a presynaptic neuronal adhesion molecule that interacts
      with postsynaptic neuroligins in both glutamatergic and GABAergic synapses and is
      important in synaptic formation and function. NRXN1 deletions increase the risk
      of schizophrenia, so our aims were to explore this in our family sample, to
      distinguish de novo from inherited mutations, to examine transmission to affected
      and unaffected siblings and to estimate penetrance. We performed copy number
      analyses in NRXN1 using data from Illumina BeadArrays from 635 subjects with
      schizophrenia (276 in genotyped families), 487 of their unaffected parents and
      309 unaffected siblings as well as 635 normal controls, all from the CBDB/NIMH
      Genetic Study of Schizophrenia. Deletions called by software were confirmed by
      quantitative PCR and comparative genome hybridization. There were deletions in 15
      individuals in 11 families, including de novo exonic deletions in one case and
      one unaffected sibling. We observed no deletions in controls, 7 deletions in
      cases (1.10%), and an unexpectedly high deletion frequency in parents (n=5,
      1.02%) and siblings (n=3, 0.97%). Three families showed inheritance from an
      unaffected parent, and in two families an unaffected parent did not transmit to
      the affected offspring. Thus we have added to the evidence that NRXN1 deletions
      are more frequent in patients with schizophrenia than in healthy individuals.
      However, the presence of de novo deletions in unaffected relatives and
      transmission from and to unaffected family members demonstrated that while the
      deletions may well have been necessary for some carriers to develop
      schizophrenia, they were not always sufficient. 

PMID- 24680032
TI  - Long-term durability of bicuspid aortic valve repair.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital cardiac
      malformation, occurring in 1% to 2% of the population. Eventually, 20% develop
      clinically important valvar regurgitation requiring surgical intervention. Aortic
      valve repair avoids anticoagulation and prosthetic valve-related complications.
      This study evaluated long-term durability of BAV repair. METHODS: From 1985 to
      2011, 728 patients, mean age 42+/-12 years, underwent BAV repair at Cleveland
      Clinic. Mean follow-up was 9.0+/-6.2 years (median, 8.3). Factors associated with
      repair durability (expressed as aortic valve reoperations and
      echocardiographically estimated gradients and regurgitation) and survival were
      identified. RESULTS: Hospital mortality was 0.41% (n=3), and stroke occurred in
      0.27% (n=2). Freedom from aortic valve reoperation at 10 years was 78%. Risk of
      reoperation was highest immediately after operation and fell rapidly to
      approximately 2.6%/year up to 15 years. Primary reasons for reoperation were cusp
      prolapse (38%), aortic stenosis or regurgitation (17%), and aortic regurgitation
      from root aneurysm (15%). Aortic valve gradients showed an early initial peak,
      rapidly declined, then rose steadily, accompanied by an increase in left
      ventricular mass. Survival was 94% at 10 years. A risk factor for early death was
      greater preoperative mitral valve regurgitation, and for late death, older age at
      operation, more severe symptoms, and poorer left ventricular function.
      CONCLUSIONS: BAV repair is safe and durable with low mortality, low prevalence of
      reoperation, and good long-term survival. Cusp prolapse from technical errors and
      natural progression of disease are the most common causes for reoperation, but
      progressive natural increase in valve gradient accounts for a substantial
      proportion as well.

PMID- 24680033
TI  - Procedure-based complications to guide informed consent: analysis of society of
      thoracic surgeons-congenital heart surgery database.
AB  - BACKGROUND: Informed consent refers to the process by which physicians and
      patients engage in a dialogue to explain and comprehend the nature, alternatives,
      and risks of a procedure or course of therapy. The goal of this study is to
      better "inform the process of informed consent" by offering empirically derived
      procedural complication lists that provide objective contemporary data that
      surgeons may share with patients and families. METHODS: The Society of Thoracic
      Surgeons Congenital Heart Surgery Database was queried for complications for 12
      congenital heart operations (2010 to 2011) performed across all Society of
      Thoracic Surgeons-European Association of Cardio-Thoracic Surgery Congenital
      Heart Surgery (STAT) risk categories. RESULTS: The 12 index procedures reviewed
      for rates of complications were repair of atrial septal defect (ASD), ventricular
      septal defect (VSD), atrioventricular septal defect (AVSD), tetralogy of Fallot
      (TOF), coarctation, and truncus arteriosus, as well as arterial switch operation
      (ASO), ASO-VSD, BiGlenn, Fontan, Norwood procedure, and systemic to pulmonary
      artery (S-P) shunt. Arrhythmia was the most frequent complication for VSD (5.8%),
      TOF (8.9%), and AVSD (14.7%) repairs. There was a high rate of sternum left open
      (planned, unplanned) for ASO (26%, 7%), ASO-VSD (29%, 10%), truncus repair (41%,
      11%), and Norwood (63%, 7%). The most frequent complications for other procedures
      include ASD (unplanned readmission, 1.9%), BiGlenn (chylothorax, 7%), Fontan
      (pleural effusion, 16%), S-P shunt (reintubation, 10.6%), and coarctation
      (reintubation, 5.2%). CONCLUSIONS: The informed consent process for congenital
      heart surgery may be served by accurate contemporary data on occurrence of
      complications. While a threshold rate of occurrence of individual complications
      may guide the physician, rare but important debilitating complications should
      also be discussed irrespective of frequency. We propose to better inform the
      process of informed consent by providing objective complications data.

PMID- 24680034
TI  - The expanding role of mitral valve repair in triple valve operations:
      contemporary North American outcomes in 8,021 patients.
AB  - BACKGROUND: Although the operative risk of multivalve operations has historically
      been high, current outcomes are poorly understood. We sought to evaluate factors
      influencing contemporary results of triple-valve operations using The Society of
      Thoracic Surgeons Adult Cardiac Surgery Database. METHODS: Among patients
      undergoing combined mitral, aortic, and tricuspid valve (triple- valve)
      operations between 1993 and 2011, aortic valve repair patients were excluded and
      those having aortic valve replacement were analyzed according to whether they
      underwent repair vs replacement of the mitral valve (MV) and tricuspid valve
      (TV). Temporal trends in operative death and clinical outcomes were examined
      using unadjusted and adjusted analyses. RESULTS: A total of 8,021 triple-valve
      patients were studied. The median (25th percentile, 75th percentile) age was 67
      years (59, 77 years), 4,809 (60%) were women, 4,488 (56%) had New York Heart
      Association class III to IV symptoms, and the mean (25th percentile, 75th
      percentile) ejection fraction was 50% (40%, 60%). MV repair was performed in
      2,728 (34%) patients overall and increased over time from 13% (1993 to 1997) to
      41% (2008 to 2011). TV repair was performed in 7,512 (94%) patients overall and
      increased over time from 86% (1993 to 1997) to 96% (2008 to 2011). Unadjusted
      operative mortality decreased from 17% in 1993 to 9% in 2011. Adjusted odds
      ratios (95% confidence intervals) of operative mortality were lower in those
      having MV repair (0.72 [0.61 to 0.85]), TV repair (0.64 [0.50 to 0.83]), and
      MV+TV repair (0.46 [0.34 to 0.63]) compared with those having replacements.
      Unadjusted and adjusted odds of stroke were similar between groups and not
      significant for all. CONCLUSIONS: This large series demonstrates that surgical
      results of triple-valve operations have continued to improve during the past 18
      years. MV and TV repair were associated with improvements in early survival.
      Although further study is required to understand late outcomes, these data
      suggest that broader efforts to perform MV repair instead of replacement in this
      high-risk patient population appear warranted.

PMID- 24680036
TI  - [Post-traumatic lens dislocation presenting as an eclipse in a patient
      demonstrating monocular blindness secondary to post-traumatic glaucoma].

PMID- 24680037
TI  - [Multifocal IOLs in the high myope, 6-year follow-up].
AB  - INTRODUCTION: Currently, the use of multifocal IOL's remains controversial for
      patients with high myopia, especially because of the risk of retinal
      complications and poor quality of vision. Our goal was to evaluate this retinal
      risk and clarify the benefits obtained in this population in terms of visual
      acuity. PATIENTS AND METHODS: Twenty-nine highly myopic patients (52 eyes with
      over 6 diopters of myopia) aged 40-69 years with early cataract by LOCSIII were
      selected for multifocal lens implantation, based on a healthy endothelium and
      retina as well as better visual acuity corrected to at least 0.5 - J2. Thirteen
      of them (21 eyes) had been previously implanted with a phakic IOL. The AT Lisa
      IOL (Zeiss(c)) was chosen because of the low powers available and ease of
      exchange. Data collection was conducted prospectively, at each visit. The main
      study parameters were the development of retinal complications, occurrence of
      PCO, patient satisfaction rate and rate of spectacle independence. RESULTS: At
      the end of the 6-year follow-up, we found 2 rhegmatogenous retinal detachments
      (3.8%) occurring at approximately 20 months and favorably treated without IOL
      explantation. We also found one case of macular atrophy secondary to cystoid
      edema. Twenty-seven uncomplicated YAG posterior capsulotomies were performed for
      posterior capsule opacification. Ninety-eight percent of patients reached best
      corrected visual acuity of at least 0.5 and 38% of at least 0.8 without
      correction. Finally, 85% of patients achieved spectacle independence, and all
      would be willing to undergo the same procedure. DISCUSSION AND CONCLUSION:
      Multifocal IOL implantation in the high myope provided favorable results at 6
      years, in carefully selected cases, providing optimal binocular visual comfort,
      including near vision. However, the fragility of the highly myopic retina
      mandates long-term follow-up. It would be beneficial to compare results of
      multifocal vs. monofocal IOL implantation in terms of visual performance and
      safety.

PMID- 24680035
TI  - Oral health, dental care and mouthwash associated with upper aerodigestive tract
      cancer risk in Europe: the ARCAGE study.
AB  - OBJECTIVE: We aimed to assess the association of oral health (OH), dental care
      (DC) and mouthwash with upper-aerodigestive tract (UADT) cancer risk, and to
      examine the extent that enzymes involved in the metabolism of alcohol modify the
      effect of mouthwash. MATERIALS AND METHODS: The study included 1963 patients with
      incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus
      and 1993 controls. Subjects were interviewed about their oral health and dental
      care behaviors (which were converted to scores of OH and DC respectively), as
      well as smoking, alcohol drinking, diet, occupations, medical conditions and
      socio-economic status. Blood samples were taken for genetic analyses. Mouthwash
      use was analyzed in relation to the presence of polymorphisms of alcohol
      metabolizing genes known to be associated with UADT. Adjusted odds ratios (ORs)
      and 95%-confidence intervals [CI] were estimated with multiple logistic
      regression models adjusting for multiple confounders. RESULTS: Fully adjusted ORs
      of low versus high scores of DC and OH were 2.36[CI=1.51-3.67] and 2.22[CI=1.45
      3.41], respectively, for all UADT sites combined. The OR for frequent use of
      mouthwash use (3 or more times/day) was 3.23[CI=1.68-6.19]. The OR for the rare
      variant ADH7 (coding for fast ethanol metabolism) was lower in mouthwash-users
      (OR=0.53[CI=0.35-0.81]) as compared to never-users (OR=0.97[CI=0.73-1.29])
      indicating effect modification (pheterogeneity=0.065) while no relevant
      differences were observed between users and non-users for the variant alleles of
      ADH1B, ADH1C or ALDH2. CONCLUSIONS: Poor OH and DC seem to be independent risk
      factors for UADT because corresponding risk estimates remain substantially
      elevated after detailed adjustment for multiple confounders. Whether mouthwash
      use may entail some risk through the alcohol content in most formulations on the
      market remains to be fully clarified.

PMID- 24680038
TI  - [Non-organic visual loss].
AB  - Functional or non-organic visual loss is a common problem in neuro-ophthalmologic
      consultation. There is a mismatch between visual acuity and/or visual field and
      the relative normality of the clinical examination. It is important to identify
      these patients so as not to prescribe unnecessary ancillary testing and so as to
      refer patients for a treatment of a possible psychiatric disorder. Conversely,
      there are many organic eye pathologies with a normal or quasi-normal fundus. We
      have at our disposal a large number of clinical and ancillary tests to
      demonstrate the non-organic nature of the visual loss: clinical examination,
      orthoptic testing, visual field, electro-physiologic tests. A rigorous diagnostic
      approach is essential to diagnose non-organic visual loss while avoiding
      diagnostic pitfalls.

PMID- 24680039
TI  - [Retinal macroaneurysms and macular hemorrhages: report of five cases].
AB  - Retinal macroaneurysm is an uncommon condition, found mainly in hypertensive
      women over age 60. We report clinical observations in five cases of complicated
      retinal macroaneurysms. These were all hypertensive women with a mean age of 80.2
      years. All retinal macroaneurysms were located in a temporal distribution
      (superior branch in 80 % of cases), proximal to the third bifurcation, and
      presented with macular hemorrhage. 4 of the 5 patients were treated surgically by
      posterior vitrectomy, and one underwent a subretinal injection of recombinant
      tissue plasminogen activator and gas tamponnade. Functional results were
      variable. Retinal atrophy secondary to the toxicity of the hemorrhage was
      observed in two cases. One macular hole was noted.

PMID- 24680040
TI  - Elevating the quality of disability and rehabilitation research: mandatory use of
      the reporting guidelines.

PMID- 24680041
TI  - Toward an agenda of quality.

PMID- 24680043
TI  - Systematic framework to evaluate the status of physical activity research for
      persons with multiple sclerosis.
AB  - BACKGROUND: Exploring the current state of health behavior research for
      individuals with multiple sclerosis is essential to understanding the next steps
      required to reducing preventable disability. A way to link research to
      translational health promotion programs is by utilizing the Behavioral
      Epidemiological Framework, which describes a sequence of phases used to
      categorize health-related behavioral research. OBJECTIVE: This critical audit of
      the literature examines the current state of physical activity research for
      persons with multiple sclerosis by utilizing the proposed Behavioral
      Epidemiological Framework. METHODS: After searching MEDLINE, PUBMED, PsycINFO,
      Google Scholar and several major areas within EBSCOHOST (2000 to present),
      retrieved articles were categorized according to the framework phases and coding
      rules. RESULTS: Of 139 articles, 49% were in phase 1 (establishing links between
      behavior and health), 18% phase 2 (developing methods for measuring behavior),
      24% phase 3 (identifying factors influencing behavior and implications for
      theory), and 9% phase 4 and 5 (evaluating interventions to change behavior and
      translating research into practice). CONCLUSIONS: Emphasis on phase 1 research
      indicates the field is in its early stages of development. Providing those with
      multiple sclerosis with necessary tools through health promotion programs is
      needed to reduce secondary conditions and co-morbidities. Reassessment of the
      field of physical activity and multiple sclerosis in the future could provide
      insight into whether the field is evolving over time or remaining stagnant.

PMID- 24680042
TI  - Health outcome disparities among subgroups of people with disabilities: a scoping
      review.
AB  - BACKGROUND: A growing body of research has found that people with disabilities
      experience lower health status and an excess burden of disease relative to the
      general US population. However, the population of people with disabilities is
      quite diverse. Thus, it is important to understand health differences between
      subgroups of people with disabilities in order to most effectively target
      interventions to address disparities. An initial step in this process is
      reviewing and synthesizing available research addressing these subgroup
      differences. OBJECTIVES: To conduct a scoping review of literature to describe
      recent research activity that has examined health outcome disparities within
      populations of people with disabilities. METHODS: We searched for relevant
      articles in MEDLINE, PsycINFO, and CINAHL databases. Three staff independently
      reviewed abstracts according to inclusion criteria. Two authors then
      independently extracted data from each included article. RESULTS: For many of the
      health outcomes of interest, there was no published literature in relation to key
      disparity factors (e.g. race, income) within the population of people with
      disabilities. The health outcomes most frequently examined were diabetes and
      heart disease. The most frequently examined disparity factors were the type of
      disabling condition and gender. CONCLUSIONS: There are significant gaps in
      available research. Building a body of research that identifies disparities and
      potentially vulnerable subgroups may improve understanding of the causes of
      disparities and contribute to efforts to improve quality of life and health
      outcomes for individuals with disabilities.

PMID- 24680044
TI  - Nutrition interventions for people with disabilities: a scoping review.
AB  - BACKGROUND: Approximately 19 percent of Americans have a disability. People with
      disabilities are at greater risk for obesity and poor nutrition, as well as
      resulting secondary conditions. CDC recommends interventions for this population
      to address this disparity. OBJECTIVE: The purpose of this article is to present
      the results of a scoping review of studies pertaining to community-based
      nutrition interventions among adults with disabilities. METHODS: Electronic
      databases were searched to discover articles pertaining to community-based
      nutrition interventions for people with disabilities. RESULTS: Sixteen journal
      articles published between 2002 and 2012 were reviewed. The reviewed community
      based nutrition interventions for adults with disabilities showed some success in
      improving health outcomes. CONCLUSIONS: There is a need for future research,
      particularly interventions with objective outcome measures and including people
      with disabilities throughout the development and implementation of programs.

PMID- 24680045
TI  - Social support, depression, and physical disability: age and diagnostic group
      effects.
AB  - BACKGROUND: Social support is an important resource that may benefit individuals
      aging with physical disabilities, although its effects may vary depending on age,
      sex, and type of disability. OBJECTIVES: To (1) examine differences in social
      support--and how support might vary as a function of age and sex--in samples of
      individuals with multiple sclerosis (MS), spinal cord injury (SCI), and muscular
      dystrophy (MD) and (2) understand the extent that associations between different
      support domains and depression might be moderated by disability diagnosis, sex
      and age. METHODS: A convenience sample (N = 1416) of individuals with MS, SCI,
      and MD completed surveys that included measures of perceived social support and
      depressive symptoms. RESULTS: No significant support differences were found
      between diagnostic groups. There was a gradual decrease in social support with
      chronological age, and women reported more support than men, particularly friend
      support. Levels of perceived friend support were negatively associated with
      depression, and the associations between social support and depression did not
      differ as a function of age, sex, or diagnosis. CONCLUSIONS: Social support is
      similarly associated with lower levels of depression for men and women, across
      disability diagnoses and all ages. Being a man and being older may be associated
      with lower levels of perceived support. Research is needed to determine if
      interventions that improve support will decrease depression and improve quality
      of life in persons with disabilities, particularly for men and individuals who
      are aging.

PMID- 24680046
TI  - The association of illness perceptions with depressive symptoms and general
      psychological distress in parents of an offspring with autism spectrum disorder.
AB  - BACKGROUND: Raising a child with an autism spectrum disorder (ASD) is a severe
      stressor and parents often present high levels of depression. Depression is
      associated with illness perceptions but this association has not been studied in
      parents of ASD offspring. OBJECTIVE: We aimed to assess the prevalence of
      psychological distress symptoms and their associations with illness perceptions
      in parents with an ASD offspring. METHODS: In 111 parents of ASD offspring we
      assessed depressive symptoms (PHQ-9), illness perceptions (B-IPQ) and general
      psychological distress (GHQ-28). Multiple linear and logistic regressions were
      used to assess their independent associations. RESULTS: The prevalence of
      parental clinically significant depressive symptoms was 34.2%, while 55%
      presented clinically significant levels of general psychological distress.
      Younger parents and those with lower financial resources had greater
      psychological distress and more severe depressive symptoms. Parents felt that the
      condition impacted their lives and believed it would be chronic. Their beliefs
      about the consequences and the chronicity of the disorder were significant
      independent correlates of their psychological distress and depressive symptoms
      severity. CONCLUSIONS: These findings indicate that a remarkable proportion of
      parents with an ASD offspring present clinically significant depressive symptoms,
      which were associated with illness perceptions relevant to the consequences and
      the chronicity of the disorder. Our data encourage psychotherapeutic
      interventions aiming to support parents to deal with the consequences and
      chronicity of their offspring's disorder, in order to reduce parental
      psychological distress.

PMID- 24680047
TI  - General health, health conditions, and current pregnancy among U.S. women with
      and without chronic physical disabilities.
AB  - BACKGROUND: Although increasing numbers of reproductive-age U.S. women with
      chronic physical disabilities (CPD) are becoming pregnant, little is known about
      their general health or comorbid health conditions. OBJECTIVES: To explore
      general health and comorbid health conditions among women with and without CPD by
      current pregnancy status. METHODS: We analyzed responses of 47,629 civilian,
      noninstitutionalized women ages 18-49 from the 2006-2011 National Health
      Interview Surveys. The survey asks about: various movement difficulties; selected
      adult health conditions; self-reported general health; and current pregnancy. We
      identified women with CPD using responses from 8 movement difficulty questions.
      RESULTS: 6043 (12.7%) women report CPD. Among nondisabled women, 3.8% report
      current pregnancy, as do 2.0% of women with CPD. Among currently pregnant women
      with CPD, 29.1% report fair or poor health, compared with only 3.2% of
      nondisabled pregnant women. Currently pregnant women both with and without CPD
      are significantly less likely to report coexisting health conditions than
      nonpregnant women. Nonetheless, among currently pregnant women with CPD, only
      24.5% report no coexisting conditions, while 28.7% report 1, 22.8% report 2,
      13.2% report 3, and 10.8% report 4-6 health conditions. In a multivariable
      regression controlling for age category, health status, and health conditions,
      CPD is not statistically significantly associated with current pregnancy.
      CONCLUSIONS: According to national survey data, it appears that pregnant women
      with CPD may have a complex mix of health problems and often experience fair or
      poor health. Better understanding the obstetrical and subspecialty needs of these
      women with multimorbidities requires additional investigation.

PMID- 24680048
TI  - The risk of developing a work disability across the adulthood years.
AB  - BACKGROUND: Work disability has implications for individual health, national
      health care expenditures, economic productivity, and the social safety net.
      Knowledge about population dynamics and risk factors associated with work
      disability are not delineated by cross-sectional research. OBJECTIVE: In this
      paper the authors estimate, for the first time, the prospective lifetime risk
      that a head of household will report a work disability. METHODS: Using forty
      years of longitudinal data from the Panel Study of Income Dynamics (PSID), we
      estimate the lifetime risk of developing a work disability and conduct a logistic
      regression analysis to examine personal characteristics that increase the
      likelihood of a self-reported work disability. Life table methods are used to
      calculate lifetime prevalence, and to compute covariate effects. RESULTS: Between
      the ages of 25 and 60, over half (54.6%) of U.S. household heads will self-report
      a work disability, and approximately one quarter (24.1%) will self-report a
      severe work disability. Persons with income below 150% of the federal poverty
      level, or lower educational attainment, have an increased likelihood of reporting
      a work disability. CONCLUSIONS: This study finds that more than half of U.S.
      household heads will self-report a work disability, which is a higher prevalence
      than in existing cross-sectional estimates. The social context for this finding
      is that work disability is a major driver of spending on health care services and
      the social safety net.

PMID- 24680049
TI  - How do disabled individuals spend their leisure time?
AB  - BACKGROUND: Despite the important role that leisure time plays in individuals'
      health, wellness and quality of life, the disability studies addressing leisure
      remain extremely limited. OBJECTIVE/HYPOTHESIS: Examine how people with
      disabilities allocate their time to leisure activities as compared to their non
      disabled counterparts. METHODS: Using data at an individual level from the Time
      Use Survey for Spain in 2002-2003 and the social model of disability as a
      framework, we estimate the determinants of time (minutes per day) spent on three
      aggregate categories (active, passive and social activities) for non-disabled,
      non-limited disabled and limited disabled individuals. RESULTS: Individuals who
      are limited in their daily activities are more likely to allocate their time to
      passive leisure (e.g., reading, television, video, and radio) and less likely to
      spend their time in social entertainment (e.g., theater, culture, and social
      events) as compared to non-disabled individuals. In addition, we find significant
      differences in minutes per day spent on leisure activities by gender, age,
      marital status and number of children. CONCLUSIONS: Accessible facilities and
      leisure installations as well as actions aimed at combating barriers and
      discrimination practices are needed to encourage participation in physical
      activity and social entertainment of people with disabilities. It is necessary to
      define, adapt and implement specific leisure activities that allow people with
      disabilities to fully participate in these activities and increase their levels
      of social integration and life satisfaction.

PMID- 24680050
TI  - Transitions in mobility, ADLs, and IADLs among working-age Medicare
      beneficiaries.
AB  - BACKGROUND: Disability is a dynamic process where functional status may change
      over time. Examination of the Medicare population suggests that, for those over
      age 65, disability status will fluctuate in 30% of beneficiaries each year. Less
      is known about those under age 65. The dynamic nature of disability is of
      relevance since it has important implications for social policies related to
      disability. OBJECTIVES: To: (1) describe the characteristics of Medicare
      beneficiaries eligible due to disability; and (2) estimate the proportion of
      individuals with transitions in functional status over a one-year period
      stratified by baseline characteristics and diagnostic subgroups. METHODS: We used
      the Medicare Current Beneficiary Survey from 1995 to 2005 to examine transitions
      in mobility and daily activities among individuals who were eligible for Medicare
      coverage due to disability. RESULTS: From the standpoint of function in mobility
      and daily activities, the working-age Medicare population with disability is
      fairly stable. While 75%-90% of our sample reported no disability or stable
      disability from one year to the next, depending on the condition and disability
      metric, as many as 13-14% of individuals showed improvement or decline in their
      functional status. CONCLUSIONS: In the working-age population with disability, a
      small percentage of individuals will improve or worsen from one year to the next.
      Since these transitions are associated with a variety of individual
      characteristics including health conditions, further research applied to larger
      samples is required to refine policy relevant models that might inform decisions
      related to ongoing eligibility for disability programs.

PMID- 24680051
TI  - Effectiveness of a multimedia outreach kit for families of wounded veterans.
AB  - BACKGROUND: Young children in military families with a member who has a life
      changing injury can experience emotional difficulties and behavior changes.
      OBJECTIVE: This study evaluated a Sesame Workshop multimedia kit called: Talk,
      Listen, Connect: Changes (TLC-II(C); 2008). The kit, which included video and
      print materials, aimed to help caregivers (i.e., at-home partner, at-home
      relative or family member of a current or discharged military member) assist
      young children as they adjusted to their parent's injury. We expected that the
      materials would be used and their quality evaluated. We hypothesized that use of
      the materials would produce improvements in caregiver and child outcomes as well
      as reductions in perceptions of disruption in the home. We also predicted that
      kit-use would have a positive impact on the family. METHODS: One-hundred and
      fifty three families with children aged 2-8 years were randomly assigned to
      receive the kit being evaluated (TLC-II(C)) or a control kit (Healthy Habits for
      Life (HHL)), also developed by Sesame Workshop. Group outcomes were compared four
      weeks following receipt of the kits using multivariate analysis of variance.
      RESULTS: All materials were well used and highly rated. All caregivers reported
      less social isolation, less child aggression, and significantly less disruptive
      home environments after kit use. Test group caregivers reported significantly
      greater reductions in depressive symptoms and significant increases in children's
      social competence over time in comparison to the control group. CONCLUSIONS:
      These results signal important improvements among families as a consequence of
      using either test or control materials. As a preventative intervention designed
      for families with an injured member, TLC-II(C) was particularly effective at
      improving coping.

PMID- 24680052
TI  - Validity of the Participation and Environment Measure for Children and Youth (PEM
      CY) for Health Impact Assessment (HIA) in sustainable development projects.
AB  - BACKGROUND: Participation in home, school, and community activities is an
      important indicator of child health and well-being. Evaluating environmental
      influences on children's participation can inform efforts to develop sustainable
      built environments, but few validated measures exist. OBJECTIVE: To examine the
      concurrent validity and utility of the Participation and Environment Measure for
      Children and Youth (PEM-CY) for Health Impact Assessment in non-urban sustainable
      development projects affecting children with disabilities. METHODS: Eighty-nine
      parents of children and youth with disabilities who identified as residing in a
      small town or rural community were sampled. Sixty-six caregivers completed the
      PEM-CY online, and 23 caregivers completed the PEM-CY and CHIEF-CP paper forms.
      Spearman correlational analyses were conducted to establish the concurrent
      validity of the PEM-CY environment sections against the CHIEF-CP. Group
      comparisons by child's age, number of functional limitations, and annual
      household income were used to examine differences in summary and item-level
      responses on the PEM-CY community section. RESULTS: Moderate to strong
      associations were found between CHIEF-CP Total Product and Magnitude Scores and
      all PEM-CY Environment Summary Scores. CHIEF-CP Physical/Structural and Policies
      Subscale Scores were most consistently associated with PEM-CY Environment Summary
      Scores. Group differences by household income were found for participation
      frequency and number of supports, including perceived availability and adequacy
      of money and information about programs and services, even when controlling
      child's age and number of functional limitations. CONCLUSION: Study results lend
      support to the use of the PEM-CY in HIA to reliably assess for environmental
      impact on children's participation. Implications for using the PEM-CY to inform
      decision-making in non-urban sustainable development projects affecting families
      of children and youth with disabilities are discussed.

PMID- 24680053
TI  - Smoking behaviors among people with disabilities in Korea.
AB  - BACKGROUND: Most reports concerning smoking behaviors in people with disabilities
      have been from Western societies; knowledge of smoking behaviors in Asian
      countries, including Korea, is insufficient. OBJECTIVES: This study investigates
      the smoking behaviors of people with a disability compared to the general
      population in Korea. METHODS: We compared the smoking behaviors of people with a
      disability with the general population by using datasets from the 2011 National
      Survey of Disabled People and an age- and sex-matched random sample from the 5th
      Korean National Health and Nutrition Examination Survey. Random samples of people
      18 years of age and older with disabilities (n = 5636) and of the general
      population were used (n = 5636). The main outcome measures include smoking
      behaviors by type, severity, and age at disability onset. RESULTS: People with a
      mental or physical impairment have higher current smoking rates (38.1% and 26.3%,
      respectively) than the general population (23.3%). In particular, current smokers
      with psychiatric impairment were more likely to smoke more than 20 cigarettes a
      day (61.2%). People with a disability, regardless of severity or age at onset,
      were less likely than the general population to have attempted to quit smoking.
      CONCLUSIONS: Smoking behaviors differed according to the type of disability.
      These results suggest that interventions for smoking prevention and cessation
      need to be tailored according to disability characteristics.

PMID- 24680054
TI  - A qualitative and quantitative analysis of the New Zealand media portrayal of
      Down syndrome.
AB  - BACKGROUND: There are only a small number of studies that systematically explore
      the tensions between the global shift to universal screening and the media
      representations of the people with Down syndrome. This paper contributes to the
      literature by analyzing the New Zealand media coverage of this topic. OBJECTIVE:
      To describe the content and quality of selected New Zealand media references to
      Down syndrome in light of the claim by New Zealand support group Saving Downs of
      state supported eugenics via universal screening. METHODS: Quantitative content
      analysis was conducted of 140 relevant New Zealand articles (from 2001 to 2011)
      and qualitative critical discourse analysis of 18 relevant articles (from 2009 to
      2011) selected from television, magazine and newspaper. RESULTS: The content
      analysis showed no strong directional reporting although the quality of life for
      people with Down syndrome was represented as slightly negative. Most articles
      focused on issues of society, government and care rather than genetics. The
      qualitative analysis identified themes around quality of life, information and
      bias, preparedness, eugenics, the visualness of disability and the need for
      public debate around genetic screening and testing. CONCLUSION: The New Zealand
      print media coverage of these issues has been relatively balanced. Recent mixed
      media coverage of the topic is critical, complex and socially inclusive of people
      with Down syndrome.

PMID- 24680055
TI  - Work participation among middle-aged persons with cerebral palsy or spina bifida-
      a longitudinal study.
AB  - BACKGROUND: Most studies of work participation among persons with cerebral palsy
      (CP) or spina bifida (SB) have focused on young adults, little is known about
      older adults. OBJECTIVE: The aim of this study was to compare work participation
      in 2009 with 1997 (98). METHODS: Two groups of persons with CP or SB in
      Gothenburg, Sweden with an IQ above 70 were interviewed using a structured
      questionnaire regarding work participation. Group (A) was studied in 1983 (n =
      55), in 1997 (n = 42) and in 2009 (n = 28). Group (B) was studied in 1998 (n =
      30) and in 2009 (n = 25). In this study, the persons interviewed in 2009 were
      compared with their own data from 1997 (8), with a non-parametric test. RESULTS:
      Work participation had significantly decreased (p < 0.004) since 1997 (8); more
      persons worked part time or had stopped working. Thirty-eight percent had
      continued their education during 1997 (8)-2009, most of them worked. Of 34
      persons working in 2009, 56% had wage subsidies, an increase from 42% in 1997
      (8). Of the persons who worked and had continued their education, 37.5% had wage
      subsidies while, among persons without continued education, 72% had this support.
      Transportation to work functioned but not as well as in 1997 (8). More persons
      used transportation for people with a disability in 2009 than in 1997 (8) and
      criticism was expressed about the transportation system. CONCLUSIONS: Results
      showed that work participation for middle-aged persons with CP or SB without
      intellectual disability decreased with age but continued education and wage
      subsidies facilitated work participation.

PMID- 24680056
TI  - Arabinose 5-phosphate isomerase as a target for antibacterial design: studies
      with substrate analogues and inhibitors.
AB  - Structural requirements of D-arabinose 5-phosphate isomerase (KdsD, E.C.
      5.3.1.13) from Pseudomonas aeruginosa were analysed in detail using advanced NMR
      techniques. We performed epitope mapping studies of the binding between the
      enzyme and the most potent KdsD inhibitors found to date, together with studies
      of a set of newly synthesised arabinose 5-phosphate (A5P) mimetics. We report
      here the first experimental evidence that KdsD may bind the furanose form of A5P,
      suggesting that catalysis of ring opening may be an important part of KdsD
      catalysis.

PMID- 24680058
TI  - Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse
      transcriptase inhibitors.
AB  - A series of CR2(OH)-diarylpyrimidine derivatives (CR2(OH)-DAPYs) featuring a
      hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were
      synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All
      the target compounds except for compound 3k displayed inhibitory activity against
      HIV-1 wild-type with EC50 values ranging from 7.21+/-1.99 to 0.067+/-0.006 MUM.
      Among them, compound 3d showed the most potent anti-HIV-1 activity (EC50=0.067+/
      0.006 MUM, SI>592), which was approximately 2-fold more potent than the reference
      drugs nevirapine (NVP) and delaviridine (DLV) in the same assay. In addition, the
      binding modes with HIV-1 RT and the preliminary SAR studies of these new
      derivatives were also investigated.

PMID- 24680059
TI  - Synthesis, molecular docking and biological evaluation of metronidazole
      derivatives containing piperazine skeleton as potential antibacterial agents.
AB  - Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of
      novel metronidazole derivatives were designed and synthesized based on
      nitroimidazole scaffold in order to find some more potent antibacterial drugs.
      For these compounds which were reported for the first time, their antibacterial
      activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis
      and Staphylococcus aureus were tested. These compounds showed good antibacterial
      activities against Gram-positive strains. Compound 4m represented the most potent
      antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 MUg/mL and
      it showed the most potent activity against S. aureus TyrRS with IC50 of 0.0024
      MUM. Molecular docking of 4m into S. aureus tyrosyl-tRNA synthetase active site
      were also performed to determine the probable binding mode.

PMID- 24680060
TI  - Effect of prime-site sequence of retro-inverso-modified HTLV-1 protease
      inhibitor.
AB  - The effects of additional substituents covering the prime-site of retro-inverso
      (RI)-modified HTLV-1 protease inhibitors containing a hydroxyethylamine isoster
      were clarified. Stereo-selective construction of the most potent isoster backbone
      was achieved by the Evans-aldol reaction. Addition of N-acetylated d-amino acid
      corresponding to the P2' site gave an RI-modified inhibitor showing superior
      inhibitory activity to the previous inhibitor. Inhibitory activities of the newly
      synthesized inhibitors suggest that partially modified RI inhibitors would
      interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine
      inhibitor. 

PMID- 24680057
TI  - Drug discovery targeting cell division proteins, microtubules and FtsZ.
AB  - Eukaryotic cell division or cytokinesis has been a major target for anticancer
      drug discovery. After the huge success of paclitaxel and docetaxel, microtubule
      stabilizing agents (MSAs) appear to have gained a premier status in the discovery
      of next-generation anticancer agents. However, the drug resistance caused by MDR,
      point mutations, and overexpression of tubulin subtypes, etc., is a serious issue
      associated with these agents. Accordingly, the discovery and development of new
      generation MSAs that can obviate various drug resistances has a significant
      meaning. In sharp contrast, prokaryotic cell division has been largely
      unexploited for the discovery and development of antibacterial drugs. However,
      recent studies on the mechanism of bacterial cytokinesis revealed that the most
      abundant and highly conserved cell division protein, FtsZ, would be an excellent
      new target for the drug discovery of next-generation antibacterial agents that
      can circumvent drug-resistances to the commonly used drugs for tuberculosis, MRSA
      and other infections. This review describes an account of our research on these
      two fronts in drug discovery, targeting eukaryotic as well as prokaryotic cell
      division. 

PMID- 24680061
TI  - Update on sexed semen technology in cattle.
AB  - The technology in current use for sexing sperm represents remarkable feats of
      engineering. These flow cytometer/cell sorters can make over 30 000 consecutive
      evaluations of individual sperm each second for each nozzle and sort the sperm
      into three containers: X-sperm, Y-sperm and unsexable plus dead sperm. Even at
      these speeds it is not economical to package sperm at standard numbers per
      inseminate. However, with excellent management, pregnancy rates in cattle with 2
      million sexed sperm per insemination dose are about 80% of those with
      conventional semen at normal sperm doses. This lowered fertility, in part due to
      damage to sperm during sorting, plus the extra cost of sexed semen limits the
      applications that are economically feasible. Even so, on the order of 2 million
      doses of bovine semen are sexed annually in the United States. The main
      application is for dairy heifers to have heifer calves, either for herd expansion
      or for sale as replacements, often for eventual export. Breeders of purebred
      cattle often use sexed semen for specific matings; thawing and then sexing frozen
      semen and immediately using the few resulting sexed sperm for in vitro
      fertilization is done with increasing frequency. Beef cattle producers are
      starting to use sexed semen to produce crossbred female replacements. Proprietary
      improvements in sperm sexing procedures, implemented in 2013, are claimed to
      improve fertility between 4 and 6 percentage points, or about 10%. 

PMID- 24680062
TI  - FTY720 impairs CD8 T-cell function independently of the sphingosine-1-phosphate
      pathway.
AB  - Fingolimod (FTY720) is a multiple sclerosis (MS) therapeutic that upon
      phosphorylation causes the internalization of sphingosine-1-phosphate receptors
      (S1PR) and traps CCR7+ T-cells in lymph nodes but relatively spares CCR7-effector
      T-cells. Nonetheless, FTY720-treated patients are more susceptible to viral
      infections, indicating a CD8 T-cell defect. Thus, the effects of FTY720 on CD8 T
      cells were investigated. To this end, we utilized experimental autoimmune
      encephalomyelitis (EAE) and a murine influenza model. CD8 T-cell trafficking,
      IFNgamma and Granzyme B (GrB) production were assessed by flow cytometry. CD8 T
      cell cytotoxic function was assessed in vitro by an LDH release assay. FTY720 not
      only ameliorated EAE by sequestering T-cells, but also reduced IFNgamma and
      Granzyme B (GrB) in splenic CD8 T-cells. Murine influenza infection was
      exacerbated and mortality was increased, as FTY720 inhibited CD8 T-cell GrB
      production and lung infiltration. Remarkably, only the unphosphorylated compound
      was able to reduce IFNgamma and GrB levels in CD8 T-cells and inhibits their
      cytotoxic function in vitro. The phosphorylated moiety had no effect in vitro,
      indicating that CD8 T-cell suppression by FTY720 is independent of S1PR
      modulation. The addition of arachidonic acid rescued CD8 T-cell function,
      suggesting that this effect may be mediated via inhibition of cytosolic
      phospholipase A2. Herein, we demonstrate that FTY720 suppresses CD8 T-cells
      independently of its trafficking effects and S1PR modulation. This provides a
      novel explanation not only for the increased rate of viral infections in FTY720
      treated patients, but also for its efficacy in MS, as CD8 T-cells have emerged as
      crucial mediators of MS pathogenesis.

PMID- 24680063
TI  - Reductions of Shiga toxin-producing Escherichia coli and Salmonella typhimurium
      on beef trim by lactic acid, levulinic acid, and sodium dodecyl sulfate
      treatments.
AB  - Studies were done at 21  degrees C to determine the bactericidal activity of
      lactic acid, levulinic acid, and sodium dodecyl sulfate (SDS) applied
      individually and in combination on Shiga toxin-producing Escherichia coli (STEC)
      in pure culture and to compare the efficacy of lactic acid and levulinic acid
      plus SDS treatments applied by spray or immersion to inactivate STEC and
      Salmonella (10(7) CFU/cm2) on beef trim pieces (10 by 10 by 7.5 cm). Application
      of 3% lactic acid for 2 min to pure cultures was shown to reduce E. coli O26:H11,
      O45:H2, O111:H8, O103:H2, O121:H2, O145:NM, and O157:H7 populations by 2.1, 0.4,
      0.3, 1.4, 0.3, 2.1, and 1.7 log CFU/ml, respectively. Treatment with 0.5%
      levulinic acid plus 0.05% SDS for <1 min reduced the populations of all STEC
      strains to undetectable levels (>6 log/ml reduction). Beef surface temperature
      was found to affect the bactericidal activity of treatment with 3 % levulinic
      acid plus 2% SDS (LV-SDS). Treating cold (4  degrees C) beef trim with LV-SDS at
      21, 62, or 81  degrees C for 30 s reduced E. coli O157:H7 by 1.0, 1.1, or 1.4 log
      CFU/cm2, respectively, whereas treating beef trim at 8  degrees C with LV-SDS at
      12  degrees C for 0.1, 1, 3, or 5 min reduced E. coli O157:H7 by 1.4, 2.4, 2.5,
      or 3.3 log CFU/cm(2), respectively. Spray treatment of beef trim at 4  degrees C
      with 5 % lactic acid only reduced the E. coli O157:H7 population by 1.3 log
      CFU/cm2. Treating beef trim at 8  degrees C with LV-SDS for 1, 2, or 3 min
      reduced Salmonella Typhimurium by 2.1, 2.6, and >5.0 log CFU/cm2, respectively.
      Hand massaging the treated beef trim substantially reduced contamination of both
      pathogens, with no detectable E. coli O157:H7 or Salmonella Typhimurium (<5
      CFU/cm2) on beef trim pieces treated with LV-SDS. Reduction of E. coli O157:H7
      and Salmonella Typhimurium populations was enhanced, but bactericidal activity
      was affected by the meat temperature.

PMID- 24680064
TI  - Immersion in antimicrobial solutions reduces Salmonella enterica and Shiga toxin
      producing Escherichia coli on beef cheek meat.
AB  - The objective of this study was to determine the effect of immersing beef cheek
      meat in antimicrobial solutions on the reduction of O157:H7 Shiga toxin-producing
      Escherichia coli (STEC), non-O157:H7 STEC, and Salmonella enterica. Beef cheek
      meat was inoculated with O157:H7 STEC, non-O157:H7 STEC, and S. enterica on both
      the adipose and muscle surfaces. The inoculated cheek meat was then immersed in
      one of seven antimicrobial solutions for 1, 2.5, or 5 min: (i) 1% Aftec 3000
      (AFTEC), (ii) 2.5% Beefxide (BX), (iii) 300 ppm of hypobromous acid (HOBR), (iv)
      2.5% lactic acid (LA2.5), (v) 5% lactic acid (LA5), (vi) 0.5% levulinic acid and
      0.05% sodium dodecyl sulfate (LEV-SDS), or (vii) 220 ppm of peroxyacetic acid
      (POA). Inoculated cheek meat was also immersed in 80  degrees C tap water (HW)
      for 10 s. In general, increasing immersion duration in antimicrobial solutions
      did not significantly (P >= 0.05) increase effectiveness. Immersion in HW for 10
      s was the most effective intervention, reducing STEC and S. enterica by 2.2 to
      2.3 log CFU/cm2 on the adipose surface and by 1.7 to 1.8 log CFU/cm2 on the
      muscle surface. Immersion for 1 min in AFTEC, BX, LA2.5, LA5, or POA was also
      effective as an intervention, reducing STEC and S. enterica by 0.8 to 2.0 log
      CFU/cm2 on the adipose surface and by 0.6 to 1.4 log CFU/cm2 on the muscle
      surface. Immersion for 1 min in HOBR or LEV-SDS was not an effective intervention
      because STEC and S. enterica reductions ranged from 0.1 to 0.4 log CFU/cm2, which
      were not significantly different (P >= 0.05) from the reductions obtained when
      cheek meat was immersed in room temperature tap water. We conclude that immersion
      of cheek meat in HW for 10 s and immersion for 1 min in AFTEC, BX, LA2.5, LA5, or
      POA effectively reduced levels of STEC and S. enterica.

PMID- 24680065
TI  - Evaluation of an attachment assay on lettuce leaves with temperature- and
      starvation-stressed Escherichia coli O157:H7 MB3885.
AB  - Attachment of enteric pathogens such as Escherichia coli O157:H7 to fresh produce
      is a crucial first step for contamination to occur, and irrigation water (IW) is
      considered a potentially important preharvest introduction route. In a natural
      situation, E. coli O157:H7 may be present in the irrigation water for some time
      and may, therefore, be starved. Most research, however, is performed with freshly
      cultured strains. The aim of this study was to examine the behavior of E. coli
      O157:H7 MB3885 under starvation stress in water used for overhead irrigation in
      the greenhouse and the consequence on its subsequent ability to attach to
      butterhead lettuce leaves. E. coli O157:H7 MB3885 was starvation stressed by
      introducing it at +/-7.5 log CFU/ml into phosphate-buffered saline (PBS), sterile
      distilled water (SDW), or IW. The suspensions were stored at 4 or 20 degrees C
      and were used after 0, 2, and 6 days for an attachment assay on butterhead
      lettuce. E. coli O157:H7 MB3885 levels were determined by plating method and live
      and dead quantitative PCR technique. A decrease in plate counts, an indicator of
      stress, was observed for most of the conditions, whereas a die-off, as revealed
      by the live and dead quantitative PCR data, was only observed in IW stored at 20
      degrees C. Overall, stress appeared to be highest in IW and lowest in PBS. The
      stressed cells were still able to recover, even at 4  degrees C, and to attach to
      the lettuce. Furthermore, our results show that standard laboratory solutions
      such as PBS and SDW may not be the best to simulate stressed cells in IW, in
      which the bacteria may behave significantly differently.

PMID- 24680066
TI  - Development of an algorithm for feed-forward chlorine dosing of lettuce wash
      operations and correlation of chlorine profile with Escherichia coli O157:H7
      inactivation.
AB  - The dynamic interactions of chlorine and organic matter during a simulated fresh
      cut produce wash process and the consequences for Escherichia coli O157:H7
      inactivation were investigated. An algorithm for a chlorine feed-forward dosing
      scheme to maintain a stable chlorine level was further developed and validated.
      Organic loads with chemical oxygen demand of 300 to 800 mg/liter were modeled
      using iceberg lettuce. Sodium hypochlorite (NaOCl) was added to the simulated
      wash solution incrementally. The solution pH, free and total chlorine, and
      oxidation-reduction potential were monitored, and chlorination breakpoint and
      chloramine humps determined. The results indicated that the E. coli O157:H7
      inactivation curve mirrored that of the free chlorine during the chlorine
      replenishment process: a slight reduction in E. coli O157:H7 was observed as the
      combined chlorine hump was approached, while the E. coli O157:H7 cell populations
      declined sharply after chlorination passed the chlorine hump and decreased to
      below the detection limit (<0.75 most probable number per ml) after the
      chlorination breakpoint was reached. While the amounts of NaOCl required for
      reaching the chloramine humps and chlorination breakpoints depended on the
      organic loads, there was a linear correlation between NaOCl input and free
      chlorine in the wash solution once NaOCl dosing passed the chlorination
      breakpoint, regardless of organic load. The data obtained were further exploited
      to develop a NaOCl dosing algorithm for maintaining a stable chlorine
      concentration in the presence of an increasing organic load. The validation tests
      results indicated that free chlorine could be maintained at target levels using
      such an algorithm, while the pH and oxidation-reduction potential were also
      stably maintained using this system. 

PMID- 24680067
TI  - Thermal resistance parameters of acid-adapted and unadapted Escherichia coli
      O157:H7 in apple-carrot juice blends: effect of organic acids and pH.
AB  - Numerous outbreaks involving fresh juices contaminated with Escherichia coli
      O157:H7 have occurred in the United States and around the world, raising concern
      for the safety of these products. Until now, only a few studies regarding the
      thermal tolerance of this pathogen in acidic juices over a wide range of pH
      values have been published. Therefore, the effect of varying the pH with
      different organic acids on the thermal inactivation of non-acid-adapted and acid
      adapted E. coli O157:H7 (strain C7927) was determined. The decimal reduction
      times (D-values) and the change in temperature required for the thermal
      destruction curve to traverse 1 log cycle (z-values) were calculated for non-acid
      adapted E. coli in an apple-carrot juice blend (80:20) adjusted to three pH
      values (3.3, 3.5, and 3.7) by the addition of lactic, malic, or acetic acid and
      at a pH of 4.5 adjusted with NaOH. Thermal parameters were also determined for
      acid-adapted cells in juices acidified with malic acid. The effect of the soluble
      solids content on the thermal tolerance was studied in samples with a pH of 3.7
      at 9.4 to 11.5  degrees Brix. The D-values were determined at 54, 56, and 58 
      degrees C, and trials were conducted in triplicate. Non-acid-adapted E. coli
      exhibited the highest thermal tolerance at pH 4.5 (D-value at 54  degrees C [D54 
      degrees C] of 20 +/- 4 min and z-value of 6.2  degrees C), although on average,
      the D-values increased significantly (P < 0.01) due to acid adaptation. In
      acidified juices, the highest tolerance was observed in acid-adapted E. coli in
      samples adjusted to pH 3.7 with malic acid (D54  degrees C of 9 +/- 2 min and z
      value of 5.4  degrees C) and the lowest in unadapted E. coli at pH 3.3 acidified
      with acetic acid (D58  degrees C of 0.03 +/- 0.01 min and z-value of 10.4 
      degrees C). For juices acidified to the same endpoint pH with different acids, E.
      coli was found to be more tolerant in samples acidified with malic acid, followed
      by lactic and acetic acids. Increasing the soluble solids content from 9.4 to
      11.5  degrees Brix showed no significant effect on the thermal tolerance of E.
      coli (P > 0.01). The data from this study will be useful for establishing
      critical limits for safe thermal processing of pH-controlled juices and similar
      products.

PMID- 24680068
TI  - Quantitative microbial risk assessment of antibacterial hand hygiene products on
      risk of shigellosis.
AB  - There are conflicting reports on whether antibacterial hand hygiene products are
      more effective than nonantibacterial products in reducing bacteria on hands and
      preventing disease. This research used new laboratory data, together with
      simulation techniques, to compare the ability of nonantibacterial and
      antibacterial products to reduce shigellosis risk. One hundred sixtythree
      subjects were used to compare five different hand treatments: two
      nonantibacterial products and three antibacterial products, i.e., 0.46%
      triclosan, 4% chlorhexidine gluconate, or 62% ethyl alcohol. Hands were
      inoculated with 5.5 to 6 log CFU Shigella; the simulated food handlers then
      washed their hands with one of the five products before handling melon balls.
      Each simulation scenario represented an event in which 100 people would be
      exposed to Shigella from melon balls that had been handled by food workers with
      Shigella on their hands. Analysis of experimental data showed that the two
      nonantibacterial treatments produced about a 2-log reduction on hands. The three
      antibacterial treatments showed log reductions greater than 3 but less than 4 on
      hands. All three antibacterial treatments resulted in statistically significantly
      lower concentration on the melon balls relative to the nonantibacterial
      treatments. A simulation that assumed 1 million Shigella bacteria on the hands
      and the use of a nonantibacterial treatment predicted that 50 to 60 cases of
      shigellosis would result (of 100 exposed). Each of the antibacterial treatments
      was predicted to result in an appreciable number of simulations for which the
      number of illness cases would be 0, with the most common number of illness cases
      being 5 (of 100 exposed). These effects maintained statistical significance from
      10(6) Shigella per hand down to as low as 100 Shigella per hand, with some
      evidence to support lower levels. This quantitative microbial risk assessment
      shows that antibacterial hand treatments can significantly reduce Shigella risk. 

PMID- 24680069
TI  - Antibiotic resistance and molecular analysis of Staphylococcus aureus isolated
      from cow's milk and dairy products in northeast Brazil.
AB  - This work aimed to assess the clonal distribution among 94 strains of
      Staphylococcus aureus isolated from cow's milk, raw cheese, and a milking machine
      in 12 dairy farms in northeast Brazil, by analyzing different typing methods and
      detecting resistance and toxigenic profiles. For the first time, isolates of this
      region were assessed simultaneously by the polymorphism of the 3'-end coa gene
      and 16S-23S rDNA, pulsed-field gel electrophoresis, antibiotic resistance
      phenotyping, and toxigenic arsenal. Although pulsed-field gel electrophoresis
      patterns showed a wider variation (discriminatory index 0.83) than the PCR-based
      methods, the internal transcribed spacer-PCR proved to be a useful and
      inexpensive procedure for conducting epidemiological surveys of S. aureus on a
      regional scale. Each dairy farm had its own resistance profile, and in two herds,
      63% of the strains were multiresistant, probably due to the indiscriminate use of
      antibiotics in bovine mastitis treatment. No methicillin-resistant S. aureus
      strains were detected in this study; however, 93.6% of S. aureus strains harbored
      variable profiles of staphylococcal enterotoxin genes seg, seh, sei, and sej.
      Transcriptional analysis revealed that 53.3% of staphylococcal enterotoxin genes
      actually transcribed, pointing out the food poisoning risk of these dairy
      products to consumers in the region. Based on the detection of the most prevalent
      clones in a herd or region, appropriate antibiotic therapy and specific
      immunization can be used for the treatment and control of staphylococcal
      mastitis. 

PMID- 24680070
TI  - Heterologous expression and characterization of tyrosine decarboxylase from
      Enterococcus faecalis R612Z1 and Enterococcus faecium R615Z1.
AB  - Tyrosine decarboxylase (TDC) is responsible for tyramine production and can
      catalyze phenylalanine to produce beta-phenylethylamine. Enterococcus strains are
      a group of bacteria predominantly producing tyramine and beta-phenylethylamine in
      water-boiled salted duck. In this study, the heterologous expression and
      characterization of two TDCs from Enterococcus faecalis R612Z1 (612TDC) and
      Enterococcus faecium R615Z1 (615TDC) were studied. The recombinant putative
      proteins of 612TDC and 615TDC were heterologously expressed in Escherichia coli.
      612TDC is a 620-amino-acid protein with a molecular mass of 70.0 kDa, whereas
      615TDC is a 625-amino-acid protein with a molecular mass of 70.3 kDa. Both 612TDC
      and 615TDC showed an optimum temperature of 25  degrees C for the tyrosine and
      phenylalanine substrates. However, 612TDC revealed maximal activity at pH 5.5,
      whereas 615TDC revealed maximal activity at pH 6.0. Kinetic studies showed that
      612TDC and 615TDC exhibited higher specificity for tyrosine than for
      phenylalanine. The catalysis abilities of both 612TDC and 615TDC for
      phenylalanine were restrained significantly with the increase in NaCl
      concentration, but this was not the case for tyrosine. This study revealed that
      the enzyme properties of the purified recombinant 612TDC and 615TDC were similar,
      although their amino acid sequences had 84% identity.

PMID- 24680071
TI  - Biofilms formed by Mycobacterium tuberculosis on cement, ceramic, and stainless
      steel surfaces and their controls.
AB  - This study assessed the biofilms formed by selected strains of Mycobacterium
      tuberculosis and investigated the efficacy of three different treatments to
      control the biofilms. Two M. tuberculosis strains were inoculated separately in
      150 ml of Middlebrook 7H9-Tween 80 (0.1%) broth with 5% liver extract and 10%
      oleic albumin dextrose catalase (OADC) supplement, 5% liver extract alone, or 10%
      OADC alone in sterile jars, each containing a 2-cm2 coupon of cement, ceramic, or
      stainless steel for biofilm development at 37  degrees C, with agitation for 2,
      3, or 4 weeks. Biofilms on the coupons were exposed to 10 ml of 2% sanitizer A or
      0.5% sanitizer B at 28 and 45  degrees C and to hot water at 85  degrees C for 5
      min. Residual biofilms on treated and untreated coupons were assessed. Both
      strains of M. tuberculosis formed biofilms on the three surfaces; however, one
      strain formed more biofilms. More biofilms were formed when media containing 5%
      liver extract was used. Biofilm mass increased as incubation time increased until
      the third week. More biofilms were formed on cement than on ceramic and stainless
      steel coupons. Sanitizing treatments at 45  degrees C removed more biofilms than
      those at 28  degrees C. However, neither treatment completely eliminated the
      biofilms.

PMID- 24680072
TI  - Identification of autoclave-resistant Anisakis simplex allergens.
AB  - Anisakis simplex is a fish parasite able to induce allergic reactions in humans
      infected when eating raw or undercooked fish parasitized with viable third-stage
      larvae. Some authors claim that exposure to nonviable Anisakis material can
      result in allergic symptoms in previously sensitized patients, indicating that
      parasite allergens are resistant to the thermal treatments of usual cooking
      procedures. Furthermore, some patients report symptoms after eating canned fish.
      The aim of this work was the analysis of parasite allergen stability in heating
      to 121  degrees C in an autoclave to simulate the thermal process applied to
      canned fish. Third-stage larvae were subjected to autoclaving for 20, 40, and 80
      min, and parasite crude extracts were analyzed by electrophoresis,
      immunoblotting, and a flow-cytometric basophil activation test. Allergens
      resistant to autoclaving were separated by reversed-phase high-performance liquid
      chromatography and identified by ion trap mass spectrometry. Protein analysis by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that autoclaving
      considerably reduced the number and intensity of identifiable protein bands in a
      time-dependent manner. Several allergens were detected by immunoblotting with a
      pool of A. simplex allergic patients' sera after autoclaving. Allergens of 9 and
      14 kDa resistant to autoclaving were identified as Ani s 4 and Ani s 1 allergens,
      respectively. Functional analysis showed that allergens retain their capacity to
      activate basophils even after autoclaving for 80 min. In conclusion, some
      relevant A. simplex allergens retain their capacity to bind immunoglobulin E and
      activate basophils after being subjected to autoclaving, which is a method
      equivalent to that used in industrial canning processes.

PMID- 24680073
TI  - Occurrence of Di-(2-ethylhexyl) adipate and phthalate plasticizers in samples of
      meat, fish, and cheese and their packaging films.
AB  - Di-(2-ethylhexyl) adipate (DEHA) and phthalates are commonly used as plasticizers
      to soften polyvinyl chloride products. Because both DEHA and certain phthalates
      have been identified as priority chemicals for assessment of human health risk
      under the Government of Canada's Chemicals Management Plan, a comprehensive
      targeted survey was conducted to investigate the occurrence of DEHA and eight
      phthalates (di-methyl phthalate, di-ethyl phthalate, di-n-butyl phthalate, di-iso
      butyl phthalate, butyl benzyl phthalate, di-n-hexyl phthalate, d-(2-ethylhexyl)
      phthalate, and di-n-octyl phthalate) in a total of 118 samples of meat (beef,
      pork, and chicken), fish, and cheese packaged mostly in cling films. The eight
      phthalates were not detected in any of the food packaging, but DEHA was detected
      in most of the cling films, indicating that although DEHA-plasticized films
      (e.g., polyvinyl chloride film) are currently being used by most grocery stores,
      nonplasticized cling films such as polyethylene film, are also being used by some
      stores. DEHA was not detected in any of the 10 cheese samples packaged in
      nonplasticized rigid plastics but was detected in all 30 cheese samples packaged
      in DEHA-plasticized cling films at levels from 0.71 to 879 MUg/g, with an average
      of 203 MUg/g. Only DEHA was detected in the beef, pork, chicken, and fish samples
      packaged in DEHA-plasticized cling films but at considerably lower levels than
      those found in cheese, with averages of 6.3, 9.1, 2.5, and 5.9 MUg/g,
      respectively. Among the eight phthalates, only di-(2-ethylhexyl) phthalate (DEHP)
      was detected in a few cheese samples at levels from 0.29 to 15 MUg/g, with an
      average of 2.8 MUg/g; these levels were very likely due to environmental
      contamination. Levels of DEHA found in most of the cheese samples from this study
      are above the European specific migration limit of 18 mg/kg for DEHA in food or
      food simulants, and levels of phthalates (i.e., DEHP) were low. 

PMID- 24680074
TI  - Challenges in performance of food safety management systems: a case of fish
      processing companies in Tanzania.
AB  - This study provides insight for food safety (FS) performance in light of the
      current performance of core FS management system (FSMS) activities and context
      riskiness of these systems to identify the opportunities for improvement of the
      FSMS. A FSMS diagnostic instrument was applied to assess the performance levels
      of FSMS activities regarding context riskiness and FS performance in 14 fish
      processing companies in Tanzania. Two clusters (cluster I and II) with average
      FSMS (level 2) operating under moderate-risk context (score 2) were identified.
      Overall, cluster I had better (score 3) FS performance than cluster II (score 2
      to 3). However, a majority of the fish companies need further improvement of
      their FSMS and reduction of context riskiness to assure good FS performance. The
      FSMS activity levels could be improved through hygienic design of equipment and
      facilities, strict raw material control, proper follow-up of critical control
      point analysis, developing specific sanitation procedures and company-specific
      sampling design and measuring plans, independent validation of preventive
      measures, and establishing comprehensive documentation and record-keeping
      systems. The risk level of the context could be reduced through automation of
      production processes (such as filleting, packaging, and sanitation) to restrict
      people's interference, recruitment of permanent high-skilled technological staff,
      and setting requirements on product use (storage and distribution conditions) on
      customers. However, such intervention measures for improvement could be taken in
      phases, starting with less expensive ones (such as sanitation procedures) that
      can be implemented in the short term to more expensive interventions (setting up
      assurance activities) to be adopted in the long term. These measures are
      essential for fish processing companies to move toward FSMS that are more
      effective. 

PMID- 24680076
TI  - Survival of Salmonella during baking of peanut butter cookies.
AB  - Peanuts and peanut-based products have been the source of recent Salmonella
      outbreaks worldwide. Because peanut butter is commonly used as an ingredient in
      baked goods, such as cookies, the potential risk of Salmonella remaining in these
      products after baking needs to be assessed. This research examines the potential
      hazard of Salmonella in peanut butter cookies when it is introduced via the
      peanut-derived ingredient. The survival of Salmonella during the baking of peanut
      butter cookies was determined. Commercial, creamy-style peanut butter was
      artificially inoculated with a five-strain Salmonella cocktail at a target
      concentration of 10(8) CFU/g. The inoculated peanut butter was then used to
      prepare peanut butter cookie dough following a standard recipe. Cookies were
      baked at 350  degrees F (177  degrees C) and were sampled after 10, 11, 12, 13,
      14, and 15 min. Temperature profiles of the oven and cookies were monitored
      during baking. The water activity and pH of the inoculated and uninoculated
      peanut butter, raw dough, and baked cookies were measured. Immediately after
      baking, cookies were cooled, and the survival of Salmonella was determined by
      direct plating or enrichment. After baking cookies for 10 min, the minimum
      reduction of Salmonella observed was 4.8 log. In cookies baked for 13 and 14 min,
      Salmonella was only detectable by enrichment reflecting a Salmonella reduction in
      the range of 5.2 to 6.2 log. Cookies baked for 15 min had no detectable
      Salmonella. Results of this study showed that proper baking will reduce
      Salmonella in peanut butter cookies by 5 log or more.

PMID- 24680075
TI  - Temperature resistance of Salmonella in low-water activity whey protein powder as
      influenced by salt content.
AB  - Salmonella can survive in low-water activity (a(w)) foods for long periods of
      time. Water activity and the presence of solutes may affect its survival during
      heating. Low-a(w) products that contain sodium levels above 0.1 % (wt/wt) and
      that have been involved in major Salmonella outbreaks include peanut products and
      salty snacks. Reduced a(w) protects against thermal inactivation. There is
      conflicting information regarding the role of salt. The aim of this study was to
      determine whether NaCl influences the survival of Salmonella in low-a(w) whey
      protein powder independent of a(w) at 70 and 80  degrees C. Whey protein powders
      of differing NaCl concentrations (0, 8, and 17 % [wt/wt]) were equilibrated to
      target a(w) levels 0.23, 0.33, and 0.58. Powders were inoculated with Salmonella,
      vacuum sealed, and stored at 70 and 80  degrees C for 48 h. Cells were recovered
      on nonselective differential media. Survival data were fit with the Weibull
      model, and first decimal reduction times (delta) (measured in minutes) and shape
      factor values (beta) were estimated. The influence of temperature, a(w), and
      salinity on Weibull model parameters (delta and beta) was analyzed using multiple
      linear regression. Results showed that a(w) significantly influenced the survival
      of Salmonella at both temperatures, increasing resistance at decreasing a(w).
      Sodium chloride did not provide additional protection or inactivation of
      Salmonella at any temperature beyond that attributed to a(w). The Weibull model
      described the survival kinetics of Salmonella well, with R2 adj and root mean
      square error values ranging from 0.59 to 0.97 and 0.27 to 1.07, respectively.
      Temperature and a(w) influenced delta values (P < 0.05), whereas no significant
      differences were found between 70 and 80  degrees C among the different salt
      concentrations (P > 0.05). beta values were not significantly influenced by
      temperature, a(w), or % NaCl (P > 0.05). This study indicates that information on
      salt content in food may not help improve predictions on the inactivation
      kinetics of Salmonella in low-a(w) protein systems within the a(w) levels and
      temperatures studied.

PMID- 24680077
TI  - Seroprevalence of hepatitis E virus in pigs from different farming systems in The
      Netherlands.
AB  - Sporadic nontravel-related hepatitis E virus (HEV) infections have been reported
      in industrialized countries. These infections are caused by zoonotic HEV
      genotypes 3 and 4 that circulate in swine, wild boar, and deer. In The
      Netherlands, HEV RNA has been detected in >50% of the pig farms, and HEV-specific
      antibodies were detected in ~70% of the slaughter pigs. In the current study, HEV
      seroprevalences were investigated in pigs raised on conventional, free-range, and
      organic farms in The Netherlands. Differences in seroprevalence may indicate
      different exposure routes or transmission dynamics within pig herds for HEV. In
      2004, serum samples of 846 fattening pigs were obtained from farms that applied
      conventional (265 pigs at 24 farms), organic (417 pigs at 42 farms), and free
      range (164 pigs at 12 farms) farming. HEV-specific antibodies were detected in
      samples from all conventional and free-range pig farms and in 41 of 42 organic
      pig farms, indicating that the probability of introducing HEV on a farm appeared
      to be equal for the different farming types. The estimated average within-herd
      seroprevalence was significantly higher for pigs raised on organic farms (89%)
      than for pigs raised on conventional farms (72%, P = 0.04) and nearly significant
      for pigs raised on free-range farms (76%, P = 0.06). Six of ten organic farms
      were estimated to have a withinherd seroprevalence of >95%, compared with 1 of 10
      and 4 of 10 of the free-range and conventional pig farms, respectively. This
      suggests a higher force of infection with HEV for pigs reared on organic farms
      compared with pigs reared on conventional or free-range farms. This may be due to
      repetitive exposure to HEV caused by farming system-specific housing conditions,
      such as a greater contact frequency between pigs and more exposure to pig manure,
      increasing the transmission rate. 

PMID- 24680078
TI  - Impact of traditional practices on food safety: a case of acute toxoplasmosis
      related to the consumption of contaminated raw pork sausage in Italy.
AB  - A case of acute toxoplasmosis in an adolescent girl, almost certainly related to
      the consumption of raw sausage, is described. The girl suffered of fever and
      weakness and presented a swollen lymph node in the submandibular region. Serology
      analysis was positive for Toxoplasma gondii and excluded other infections.
      Further analysis, with avidity test and immunoblot, confirmed the acute
      toxoplasmosis. She reported that about a month before the appearance of the
      symptoms, she had eaten a piece of raw sausage while it was being prepared by her
      father. We analyzed sausage samples prepared from this same batch that had been
      frozen for later consumption, and they demonstrated evidence of T. gondii DNA
      when using a specific nested PCR assay. The sausage was prepared from the meat of
      a pig that had been backyard raised and slaughtered at home, a traditional
      practice in rural communities in many countries. The tasting of fresh prepared
      raw sausage is a common practice throughout Italy, and it could be a major cause
      for toxoplasmosis as suggested by the results of a questionnaire administered in
      the province of Palermo, Sicily. Contact with cats and, to a lesser extent, raw
      salad consumption were also referred to as presumptive causes for the symptomatic
      cases. Two additional cases of acute toxoplasmosis reported during questionnaire
      administration were alleged to have been caused by the consumption of fresh
      sausage made with the meat of a pig raised in the yard. Traditional practices in
      animal farming, and the processing of meat from animals raised in the backyard or
      meat from wild game animals, might have a big impact on food safety. 

PMID- 24680079
TI  - Benzopyrone coumarin leads to an inhibition of ochratoxin biosynthesis in
      representatives of Aspergillus and Penicillium spp. via a type of feedback
      response mechanism.
AB  - Growth and mycotoxin biosynthesis of the ochratoxin-producing fungal strains
      Aspergillus carbonarius, Aspergillus steynii, Penicillium verrucosum, and
      Penicillium nordium were analyzed on standard laboratory growth medium
      supplemented with different amounts of coumarin, an organic compound of the
      benzopyrone class. Neither the growth nor the phenotypic morphology of the
      filamentous fungi analyzed was affected by using coumarin concentrations
      equivalent to 2.5 to 25 MUg/ml of medium. In contrast, the ochratoxin
      biosynthesis was strongly inhibited in both strains of the Aspergillus species
      and nearly completely inhibited in both Penicillium strains at coumarin
      concentrations above 8.75 MUg/ml. Analyzing the transcriptional activity of the
      otapksPN polyketide synthase gene in P. nordicum using real-time PCR revealed a
      strong concentration-dependent decrease in gene expression. Taken together, the
      data show that ochratoxin biosynthesis in representative strains of the genera
      Aspergillus and Penicillium could be effectively inhibited by coumarin in a
      concentration-dependent manner. It could be suggested that the molecular
      background behind this inhibition is some kind of feedback response mechanism,
      based on the structural similarity of coumarin to the benzopyrone moiety of the
      ochratoxin molecule. 

PMID- 24680080
TI  - Reliable and simple detection of ochratoxin and fumonisin production in black
      Aspergillus.
AB  - To date, edible fungi such as black Aspergillus (Aspergillus niger aggregates)
      have been considered as safe. However, it has recently been reported that some
      strains have a mycotoxin biosynthetic capability, and this capability must be
      evaluated to determine the safety of edible fungi. In this study, we assessed the
      ability of mycotoxin production in A. niger aggregates isolated from various
      Korean foods using multiplex PCR and high-performance liquid chromatography
      (HPLC) analyses. Multiplex PCR and HPLC analyses of 32 A. niger aggregates showed
      that ochratoxin and fumonisin were produced only by strains exhibiting positive
      PCR patterns with ochratoxin and fumonisin biosynthesis genes. However, several
      strains did not produce mycotoxins, even though they contained mycotoxin
      biosynthesis genes. Using multiplex PCR pattern and HPLC analyses, we selected
      Aspergillus strains that do not produce mycotoxins, which will contribute to the
      development of safer fermented foods. 

PMID- 24680081
TI  - Evaluation of content and estimation of daily intake of cadmium and lead in
      several varieties of potatoes (Solanum tuberosum L.) cultivated in the Canary
      Islands (Spain).
AB  - Monitoring the metal content in foods such as potatoes is an important aspect of
      food safety and regulation. Samples of nine varieties of potatoes (73 samples of
      local potatoes and 77 samples of imported potatoes) were randomly obtained from
      supermarkets, farmers markets, and farmer plots in Tenerife (Canary Islands,
      Spain). The edible portion (pulp) was the only part considered for analysis
      because Spaniards traditionally eat only peeled potatoes. Cadmium (Cd) and lead
      (Pb) were determined using graphite furnace atomic absorption spectrometry. Cd
      concentrations ranged from 0.006 mg/kg in the Cara and Negra varieties to 0.019
      mg/kg in the Bonita variety, and Pb concentrations ranged from 0.007 mg/kg in the
      Up-to-date variety to 0.023 mg/kg in the Recara variety. The mean concentrations
      of Cd (0.01 mg/kg) and Pb (0.014 mg/kg) were below the limits established by
      European regulations for potatoes (0.1 mg/kg of wet weight for each metal). Based
      on a mean consumption of 143.2 g of potato per person per day for the Canary
      Islands population, the mean daily intakes of Cd (0.015 mg/day) and Pb (0.023
      mg/day) were below the legislated respective tolerable weekly intakes. Thus, the
      samples analyzed were considered safe to eat with regard to the metal
      concentrations found. 

PMID- 24680083
TI  - Assessment criteria and approaches for rapid detection methods to be used in the
      food industry.
AB  - The number of commercially available kits and methods for rapid detection of
      foodborne pathogens continues to increase at a considerable pace, and the
      diversity of methods and assay formats is reaching a point where it is very
      difficult even for experts to weigh the advantages and disadvantages of different
      methods and to decide which methods to choose for a certain testing need.
      Although a number of documents outline quantitative criteria that can be used to
      evaluate different detection methods (e.g., exclusivity and inclusivity), a
      diversity of criteria is typically used by industry to select specific methods
      that are used for pathogen detection. This article is intended to provide an
      overall outline of criteria that the food industry can use to evaluate new rapid
      detection methods, with a specific focus on nucleic acid-based detection methods.

PMID- 24680082
TI  - Evaluation of arsenate content of rice and rice bran purchased from local markets
      in the People's Republic of China.
AB  - In previous studies, inorganic arsenic and total arsenic concentrations in rice
      bran have been much higher than those in polished rice obtained from the same
      whole paddy rice. However, the arsenic species distribution between rice and bran
      is still unknown, especially for arsenite (AsIII) and arsenate (AsV). To
      characterize the arsenic species in rice and bran and explain the elevated
      concentrations of inorganic arsenic and total arsenic, four arsenic species,
      AsIII, AsV, dimethylarsinic acid, and monomethylarsonic acid, were evaluated.
      Rice and bran samples (n = 108) purchased from local markets in the People's
      Republic of China were analyzed using high-performance liquid chromatography with
      hydride generation and atomic fluorescence spectrometry and then microwave
      extraction. As expected, most of the arsenic was found in bran, with bran/rice
      ratios of 6.8 for total arsenic species and 6.4 for inorganic arsenic. Among four
      arsenic species, the maximum bran/rice ratio was 104.7 (335/3.2 MUg kg(-1)) for
      AsV followed by 1.2 (69.2/56.1) for AsIII, 1.3 (6.7/5.2) for dimethylarsinic
      acid, and 4.0 (0.8/0.2) for monomethylarsonic acid. Thus, the large difference in
      arsenic concentration between rice and bran was mostly due to the difference in
      the AsV concentration, which account for 96 and 95 % of the difference for total
      arsenic species and inorganic arsenic, respectively. Therefore, the possibility
      of AsV contamination in rice bran and its by-products needs more study. This
      study is the first in which concentrations of AsIII and AsV in rice and bran have
      been documented, revealing that a higher percentage of AsV occurs in bran than in
      rice. 

PMID- 24680084
TI  - Does response to induction chemotherapy (IC) predict locoregional control after
      concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer
      (LAHNC)?

PMID- 24680085
TI  - Prevalence of intracranial stenosis in a Norwegian ischemic stroke population.
AB  - BACKGROUND: There is no data about prevalence of intracranial stenosis (IS) in
      Northern Europe. This study aimed to investigate the prevalence of symptomatic
      and asymptomatic IS in a Norwegian, community-based ischemic stroke population.
      METHODS: In a prospective study, all ischemic stroke or transient ischemic attack
      (TIA) patients were screened for IS by transcranial color-coded sonography,
      magnetic resonance angiography, and/or computed tomography angiography. Patients
      with IS and any cardiac arrhythmia or other possible causes of IS than
      atherosclerosis were excluded. IS was defined as symptomatic if the
      infarct/symptoms were related to the territory of the stenotic artery. Risk
      factors for cerebrovascular disease were registered on admission. RESULTS: During
      an 18-month study period, 607 patients had an ischemic stroke or a TIA. Out of 69
      patients with IS (11.4%), 7 patients were excluded because having atrial
      fibrillation, and IS of possible atherosclerotic etiology was therefore diagnosed
      in 62 patients (10.2%). IS was symptomatic in 45 patients (7.4%). Diabetes
      mellitus was the only risk factor significantly associated with symptomatic IS
      (odds ratio 2.39, 95% confidence interval [CI] 1.03-5.54, P=.04). CONCLUSIONS: IS
      occurs in approximately 10% and is symptomatic in about 7% of a Norwegian
      ischemic stroke/TIA population. Diabetes mellitus appears to be the major risk
      factor for IS.

PMID- 24680086
TI  - Stroke education using an animated cartoon and a manga for junior high school
      students.
AB  - BACKGROUND: We investigated whether junior high school students could be educated
      regarding stroke with an animated cartoon and a Manga that we produced for the
      purpose of dissemination of this knowledge. METHODS: We produced a 10-minute
      animated cartoon and a Manga that provided information regarding stroke risk
      factors, stroke signs and symptoms, and awareness to immediately contact emergent
      medical service (EMS) on identification of stroke signs and symptoms. From
      December 2011 to March 2012, 493 students in 15 classes of the first grade (age
      12-13 years) of 3 junior high schools were enrolled in the study. Each subject
      watched the animated cartoon and read the Manga; this was referred to as
      "training." Lessons about stroke were not given. Questionnaires on stroke
      knowledge were evaluated at baseline, immediately after the training, and 3
      months after the training. RESULTS: The proportion of correct answers given
      immediately after the training was higher for all questions, except those related
      to arrhythmia, compared with baseline. Percentage of correct answers given at 3
      months was higher than that at baseline in questions related to facial palsy (75%
      versus 33%), speech disturbance (91% versus 60%), hemiplegia (79% versus 52%),
      numbness of 1 side (58% versus 51%), calling for EMS (90% versus 85%), alcohol
      intake (96% versus 72%), and smoking (69% versus 54%). At 3 months after the
      training, 56% of students answered the FAST (facial droop, arm weakness, speech
      disturbance, time to call for EMS) mnemonic correctly. CONCLUSIONS: Stroke
      education using these teaching aids of the animated cartoon and the Manga
      improved stroke knowledge in junior high school students.

PMID- 24680087
TI  - Tranexamic acid for spontaneous intracerebral hemorrhage: a randomized controlled
      pilot trial (ISRCTN50867461).
AB  - BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) can be devastating,
      particularly if hematoma expansion (HE) occurs. Tranexamic acid (TA), an
      antifibrinolytic drug, significantly reduced mortality in bleeding patients after
      trauma in the large CRASH-2 trial. The CRASH-2 ICH substudy found that TA
      nonsignificantly reduced mortality and dependency in traumatic ICH. The aim of
      this study was to assess the feasibility of performing a randomized controlled
      trial of tranexamic acid in spontaneous ICH, ahead of a definitive study.
      METHODS: We performed a single-center, prospective, randomized (2:1), double
      blind, placebo-controlled blinded endpoint trial of TA (intravenous 1 g bolus, 1
      g infusion/8 h) in acute (<24 hours) spontaneous ICH. The primary objective was
      to test the feasibility of recruiting to the trial. Other objectives included
      tolerability (adverse events) and the effect of TA on HE and death and
      dependency. RESULTS: The trial was feasible, with 24 patients enrolled (TA, n=16;
      placebo, n=8) between March 2011 and March 2012, and acceptable-only 3 patients
      declined to participate. All patients received the correct randomized treatment;
      1 patient in the TA group did not complete the infusion because of neurologic
      deterioration. There were no significant differences in secondary outcomes
      including adverse events, HE, death, and dependency. One patient in the TA group
      had a deep vein thrombosis . CONCLUSIONS: This, the first randomized controlled
      trial of TA in ICH, found that the protocol could be delivered on schedule (2
      patients/mo) and was feasible. Larger studies are needed to assess safety and
      efficacy of TA in ICH.

PMID- 24680088
TI  - Analysis of the interleukin-1 receptor antagonist gene variable number tandem
      repeats in ischemic stroke.
AB  - BACKGROUND: There is an increasing interest in the role of inflammatory
      mechanisms contributing to the development of stroke. Recent studies have
      reported an association between allele 2 of a variable number tandem repeat of
      the interleukin-1 receptor antagonist (IL1RN) gene in Caucasian patients with
      ischemic stroke. The purpose of this investigation is to independently confirm
      these results in our study population. METHODS: We recruited and genotyped 516
      Caucasian patients with ischemic stroke and 380 matched controls. Tests of
      association were performed to estimate odds ratio (OR) for the IL1RN gene
      variable number tandem repeat polymorphism with case-control status. Genotype
      frequencies of IL1RN gene were compared by case-control and symptom status using
      chi2 contingency tables and logistic regression models. RESULTS: No significant
      association was observed between any of the IL1RN gene genotypes and ischemic
      stroke. The unadjusted association model a, and the fully saturated model e,
      adjusted for age, gender, and stroke risk factors demonstrated no significant
      increase in risk associated with the IL1RN gene 2/2 genotype (a: OR, 1.11; 95%
      confidence interval [CI], .67-1.89; P=.615; and e: OR, .95; 95% CI, .46-1.94;
      P=.574). Analyses of genotypic and allelic frequencies of each Trial of Org 10172
      in Acute Stroke Treatment subtype with control and pairwise comparison between
      stroke subtypes did not show any significant differences in their distributions,
      and all P values were greater than the significance level of .05. CONCLUSION: Our
      results do not confirm an association between the gene and ischemic stroke in
      Caucasian patients.

PMID- 24680090
TI  - The long-term nutritional status in stroke patients and its predictive factors.
AB  - BACKGROUND: Malnutrition is common in the first few months after stroke and
      contributes to a poor overall outcome. We analyzed long-term weight changes and
      their predictive factors. METHODS: A total of 71 first-ever stroke patients were
      included in the study and examined (1) their weight on admission to the acute
      stroke unit (usual weight [UW]), on admission to the rehabilitation unit, on
      discharge from the rehabilitation unit, and then 1 year or more after the stroke
      (median time: 2.5 years), (2) the presence of malnutrition after stroke, and (3)
      possible predictive factors, namely, sociodemographic factors, clinical
      characteristics (concerning the stroke, the patient's current neurologic status
      and the presence of diabetes mellitus and depression), and the present
      nutritional state (including eating difficulties, anorexia, and changes in food
      intake and food preferences). RESULTS: Body weight fell (4.0 kg) during the
      patients' stay in the stroke unit, increased moderately in the rehabilitation
      unit (2.0 kg), and returned to the UW by the long-term measurement. However, at
      the last observation, 40.1% of the patients weighed markedly less than their UW,
      38.0% weighed markedly more, and 21.1% were relatively stable. Predictors of
      weight change were a change in preferences for sweet food products and a change
      in food intake. Malnutrition was frequent (47.9%) and associated with reduced
      food intake, residence in an institution, and diabetes mellitus. CONCLUSIONS:
      Malnutrition was highly prevalent, with an important role of change in food
      intake and food preferences, which could result from brain lesions and specific
      regimens. Living in an institution needs consideration, as its negative effects
      can be prevented.

PMID- 24680089
TI  - Cerebral microbleeds and asymptomatic cerebral infarctions in patients with
      atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is a cardiac arrhythmia that does not
      infrequently induce ischemic strokes; however, little research has been reported
      on focal cerebral microangiopathic lesions in patients with AF. Recently cerebral
      microbleeds (CMBs) have been noticed for their potential implication in cerebral
      small vessel disease. Therefore, we had 2 goals in the present study: (1) to
      compare the prevalence of CMBs in patients with AF with that in patients without
      AF, and (2) to prove that CMBs could be a clinical predictive factor for the
      development of future cerebral microangiopathy in patients with AF without a
      history of symptomatic cerebral infarction in a prospective manner. METHODS: We
      performed yearly brain magnetic resonance imaging (MRI) assessments for a maximum
      of 5 years in 131 patients with AF and 112 control patients. Seventy-seven
      patients with AF underwent more than 3 yearly MRI scans. RESULTS: The Kaplan
      Meier curve showed that the development of an asymptomatic cerebral infarction
      (ACI) was associated with the baseline presence of a CMB (P=.004). A multivariate
      Cox regression analysis revealed that the CMBs at baseline were significantly
      associated with an increment in not only the occurrence of ACIs (hazard ratio
      [HR], 5.414; 95% confidence interval [CI], 1.03-28.43; P=.046) but also in the
      consecutive development of CMBs (HR, 6.274; 95% CI, 1.43-27.56; P=.015).
      CONCLUSIONS: Patients with AF had a significantly higher prevalence of CMBs. The
      presence of CMBs in the baseline MRI may predict the consequent onset of an ACI
      and increase in CMBs in patients with AF.

PMID- 24680091
TI  - Perfect--the enemy of good.
AB  - Our article has limitations, which we thoroughly describe. However, as the
      article highlights, wheelchairs are requiring repairs much too often, the repairs
      are causing significant consequences for users, and the problem is getting worse.
      The commentary concludes that producing a strong study will be difficult and of
      limited value, but offers no call for better, larger studies or suggestions for
      improvements. We believe there is much to be learned from our data, and our
      conclusion is that we need to do better. We need more information, larger
      cohorts, and better methods. It is the best way to cause changes that will
      positively impact the millions of wheelchair users around the world. 

PMID- 24680092
TI  - Headaches after traumatic brain injury.

PMID- 24680093
TI  - Response to letter regarding 'Does the addition of deep breathing exercises to
      physiotherapy-directed early mobilisation on high-risk open upper abdominal
      surgery alter patient outcomes? Cluster randomised controlled trial'.

PMID- 24680094
TI  - Normative data for hand grip strength in healthy children measured with a bulb
      dynamometer: a cross-sectional study.
AB  - OBJECTIVE: To present the normative hand grip strength values measured with a
      bulb dynamometer for children, by gender and age, and to correlate the findings
      with weight, height, body composition and handedness. DESIGN: Cross-sectional
      study. PARTICIPANTS: Data from 295 healthy children of both genders aged 6 to 13
      years were analysed. METHODS: Weight, height, body composition (Biodynamics model
      450 bioimpedance analyser), handedness (Edinburgh scale) and grip strength
      measured with a bulb dynamometer (North Coast) were obtained. RESULTS: Grip
      strength of both hands increased with age in the two genders. Grip strength was
      similar in boys and girls between 6 and 13 years of age. The dominant hand was
      stronger than the non-dominant hand [mean (standard deviation) 7.0 (2.3)psi vs
      6.5 (2.1)psi], with a mean difference of 0.52psi (95% confidence interval of the
      difference 0.46 to 0.58). Grip strength was positively correlated with fat-free
      mass and height (r>=0.75). CONCLUSION: This study provides normative values for
      hand grip strength measured with a bulb dynamometer in children aged 6 to 13
      years. This dynamometer provides a simple method to measure grip strength, and
      the results of this study provide further evidence of its performance in the
      measurement of grip strength.

PMID- 24680095
TI  - Additional thoughts on 'Does the addition of deep breathing exercises to
      physiotherapy-directed mobilisation alter patient outcomes following high-risk
      open upper abdominal surgery? Cluster randomised controlled trial'.

PMID- 24680096
TI  - Calculating the costs of an 8-week, physiotherapy-led exercise intervention in
      deconditioned cancer survivors in the early survivorship period (the PEACH
      trial).
AB  - Strong evidence exists for rehabilitation programmes following a cancer
      diagnosis, although little is known about their cost. The effects of an 8-week,
      physiotherapy-led, structured group intervention during the early survivorship
      phase were evaluated. Significant changes in quality of life and fatigue, and
      promising changes in fitness were found. The overall cost for this programme was
      ?196 per participant, including the salaries of the clinicians, overheads and
      equipment costs. The modest costs associated with this programme may support more
      routine 'cancer rehabilitation', although more robust analyses are required. 

PMID- 24680097
TI  - Statistical parsing of varieties of clinical Finnish.
AB  - OBJECTIVES: In this paper, we study the development and domain-adaptation of
      statistical syntactic parsers for three different clinical domains in Finnish.
      METHODS AND MATERIALS: The materials include text from daily nursing notes
      written by nurses in an intensive care unit, physicians' notes from cardiology
      patients' health records, and daily nursing notes from cardiology patients'
      health records. The parsing is performed with the statistical parser of Bohnet
      (http://code.google.com/p/mate-tools/, accessed: 22 November 2013). RESULTS: A
      parser trained only on general language performs poorly in all clinical
      subdomains, the labelled attachment score (LAS) ranging from 59.4% to 71.4%,
      whereas domain data combined with general language gives better results, the LAS
      varying between 67.2% and 81.7%. However, even a small amount of clinical domain
      data quickly outperforms this and also clinical data from other domains is more
      beneficial (LAS 71.3-80.0%) than general language only. The best results (LAS
      77.4-84.6%) are achieved by using as training data the combination of all the
      clinical treebanks. CONCLUSIONS: In order to develop a good syntactic parser for
      clinical language variants, a general language resource is not mandatory, while
      data from clinical fields is. However, in addition to the exact same clinical
      domain, also data from other clinical domains is useful.

PMID- 24680098
TI  - Perceived effectiveness of teaching methods for point of care ultrasound.
AB  - BACKGROUND: Point of care ultrasound (POCUS) is a rapidly expanding aspect of
      both the practice and education of emergency physicians. The most effective
      methods of teaching these valuable skills have not been explored. OBJECTIVE: This
      project aimed to identify those methods that provide the best educational value
      as determined by the learner. METHODS: Data was collected from pre- and post
      course surveys administered to students of the introductory POCUS course provided
      to emergency medicine residents each year at our facility. Data were collected in
      2010 and 2011. Participants were asked to evaluate the effectiveness of small-
      vs. large-group format, still images vs. video clips, and PowerPoint slides vs.
      live demonstration vs. hands-on scanning. RESULTS: Students felt the most
      effective methods to be small-group format, video-clip examples, and hands-on
      scanning sessions. Students also rated hands-on sessions, still images, and video
      images as more effective in post-course surveys as compared with pre-course
      surveys. CONCLUSIONS: The methods perceived as most effective for POCUS education
      are small-group format, video-clip examples, and hands-on scanning sessions.

PMID- 24680099
TI  - Faux fracture.

PMID- 24680100
TI  - Hand sanitization rates in an urban emergency medical services system.
AB  - BACKGROUND: Hand sanitizing, although often a "forgotten" practice, has been
      demonstrated to be a leading factor in preventing infectious disease transmission
      in health care environments. Previous studies have looked at hand-sanitization
      rates in hospital settings, but we are aware of very few describing this in the
      prehospital setting. Because emergency medical services (EMS) providers are
      potential vectors of infectious disease spread, it is important to know if their
      hand-sanitization practices are sufficient. OBJECTIVE: The objective of this
      study was to describe the hand-sanitization rates for a convenience sample of an
      urban EMS system. METHODS: A convenience sampling of paramedics employed by an
      urban paramedic ambulance service (55,000+ runs/year) underwent prospective,
      blinded observation during a 6-month period. Observations were conducted by
      paramedic students during 8-h and 12-h shifts. Recorded data points included any
      modality of hand sanitizing (e.g., soap/water, anti-germicidal gels or foams,
      anti-germicidal wipes) immediately surrounding all patient contacts and meals.
      Glove use during patient contact was also recorded. Trips to the restroom were
      not directly observed and hand sanitizing after this event was assumed. Duration
      of any sanitizing event was not recorded. Data points were analyzed using simple
      and descriptive statistics. RESULTS: Fifty-three paramedics (of 108 paramedic
      employees) were observed during 258 patient contacts. Paramedics were observed to
      sanitize their hands after 162 of these (62.8%). If hand sanitizing is assumed in
      the 16 immediate trips to the restroom after patient contact, the compliance rate
      increased to 68.9%. Hands were sanitized immediately before patient contact only
      three times (1.1%) and nine times during patient contact (3.5%). Gloves were not
      worn during 32 of the patient contacts (12.4%). Hand sanitizing occurred before 8
      of 42 meals (19%) and after 25 of 42 meals (59.5%). CONCLUSIONS: Hand
      sanitization events were noted in this convenience sample group a majority of
      times in association with patient contact. However, there appears to be
      substantial room for improvement. This suggests that EMS services should work to
      improve hand-sanitization compliance. Increased instruction, education, or access
      to hygiene equipment should be investigated as avenues to improve future
      compliance.

PMID- 24680101
TI  - Altered mental status due to pruno intoxication.
AB  - BACKGROUND: The diagnosis of alcohol intoxication might not be considered in
      patients coming from locations where access to alcohol is severely restricted or
      not permitted. OBJECTIVE: We present a case of alcohol intoxication in a patient
      presenting from a military prison. The patient ingested an alcoholic beverage
      made in his prison cell with produce stolen from the prison cafeteria. We also
      discuss potential complications of "prison-brewed" alcoholic beverages. CASE
      REPORT: A 22-year-old male presented to the emergency department after being
      found in his cell with a depressed level of consciousness and next to a mouthwash
      bottle filled with a foul-smelling liquid. Physical examination revealed a heart
      rate of 111 beats/min, a Glasgow Coma Scale score of 11, no signs of injury or
      track marks on the skin, and intermittent agitation alternating with somnolence.
      Laboratory evaluation was significant for a serum ethanol level of 279 mg/dL.
      After a period of observation, mental status returned to normal and the patient
      admitted to making "pruno." CONCLUSIONS: Alcohol intoxication might be unexpected
      or not considered in patients that should have no access to common sources of
      ethanol. Awareness of methods of novel fermentation, even in incarcerated
      individuals, can assist in the differential diagnosis of patients presenting with
      altered mental status.

PMID- 24680102
TI  - Is pelvic ultrasound associated with an increased time to appendectomy in
      pediatric appendicitis?
AB  - BACKGROUND: Appendicitis is a common pediatric condition requiring urgent
      surgical intervention to prevent complications. Pelvic ultrasound (US) as a
      diagnostic aid has become increasingly common. Despite its advantages, evidence
      suggests US can lead to delayed definitive management. OBJECTIVE: The objective
      was to test the hypothesis that US is associated with an increased time to
      appendectomy in children with acute appendicitis. METHODS: A chart review was
      conducted of all children aged 0-17 years who presented to the pediatric
      emergency department (ED) with a discharge diagnosis of appendicitis. The primary
      outcome variable was the interval between initial evaluation to appendectomy
      between patients who received an US and those who did not. RESULTS: Of 662 cases
      included, 424 patients (64%) underwent a pelvic US and 238 patients underwent an
      appendectomy without US. Median time interval from initial evaluation in the ED
      by a physician to appendectomy among patients who received an US was 9.7 h
      (interquartile range [IQR]: 6.8-15.0 h) compared with 5.5 h (IQR: 3.8-8.6 h)
      among patients who did not receive an US (Mann-Whitney, p < 0.001). The increased
      time to appendectomy in patients who received an US was dependent on the patient
      being female and presenting to the ED after hours (univariate analysis of
      variance test for interaction, p < 0.05). CONCLUSIONS: Female pediatric patients
      and those presenting after hours that undergo an US have a significantly
      increased time to appendectomy compared with those who do not undergo diagnostic
      imaging.

PMID- 24680103
TI  - Unusual complication of a central venous catheter in a thoracoabdominal trauma.

PMID- 24680104
TI  - Incidence of infection after Mohs micrographic and dermatologic surgery before
      and after implementation of new sterilization guidelines.
AB  - BACKGROUND: Clinical guidelines regarding surgical instrument sterilization
      established by accrediting organizations should be based on peer-reviewed
      scientific literature. Few data exist in the scientific literature to support the
      changes in sterilization protocols imposed by accrediting organizations.
      OBJECTIVE: We sought to determine whether recently established guidelines for the
      sterilization of surgical instruments have had any clinical impact on
      postsurgical infection rates. METHODS: Infections rates after excisional and Mohs
      micrographic surgery before and after implementation of new Joint Commission on
      the Accreditation of Healthcare Organizations sterilization guidelines were
      examined retrospectively. All surgeries were performed at an academic outpatient
      office. RESULTS: In all, 1415 patients underwent a total of 1688 surgeries. No
      significant differences were observed in mean patient age (P = .113), mean number
      of Mohs micrographic surgical levels (P = .067), final defect size (P = .305),
      patient gender (P = .072), repair type (P = .691), or infection rate (P = .453).
      No major differences in predisposing factors were identified in patients who
      developed postsurgical infections. LIMITATIONS: This was a retrospective study
      conducted at a single academic institution. CONCLUSIONS: In our practice, recent
      changes in surgical instrument sterilization protocols have had no impact on
      postsurgical infection rates. The implementation of such guidelines places an
      additional burden on the health care system without providing any improvement in
      patient outcomes.

PMID- 24680105
TI  - Effectiveness of standard lavage with supplemental chlorhexidine in patients
      undergoing chemical matricectomy for ingrown toenails: a clinical trial.
AB  - BACKGROUND: Phenolization is often used to treat ingrown toenails. Alcohol lavage
      with or without supplemental chlorhexidine may be used to remove residual phenol,
      which can contribute to side effects such as persistent oozing or drainage.
      OBJECTIVE: We sought to compare the effectiveness in removing residual phenol of
      lavage with alcohol plus chlorhexidine versus alcohol alone. METHODS: We studied
      80 patients who underwent unilateral phenol matricectomy: 40 who received
      irrigation with alcohol alone and 40 who received irrigation with alcohol plus
      chlorhexidine. Phenol levels were measured after each of 5 rounds of 3-mL
      irrigations. RESULTS: After the first irrigation, an average of 44.92% and 38.35%
      of the phenol remained in the nailfold in the alcohol and the
      alcohol/chlorhexidine groups, respectively (P < .05). After all 5 irrigations, no
      difference in efficacy between the 2 solutions was found (P > .005). LIMITATIONS:
      It was not possible to calculate the quantity of phenol initially introduced into
      the nail bed. The percentage remaining was calculated from the total amount of
      phenol recovered. CONCLUSION: When a single irrigation step is performed after
      phenolization, alcohol plus chlorhexidine is more effective than alcohol alone
      for removing residual phenol. When multiple irrigations are performed, the 2
      solutions are equally effective.

PMID- 24680106
TI  - The effects of coral bleaching on settlement preferences and growth of juvenile
      butterflyfishes.
AB  - Coral bleaching and associated mortality is an increasingly prominent threat to
      coral reef ecosystems. Although the effects of bleaching-induced coral mortality
      on reef fishes have been well demonstrated, corals can remain bleached for
      several weeks prior to recovery or death and little is known about how bleaching
      affects resident fishes during this time period. This study compared growth rates
      of two species of juvenile butterflyfishes (Chaetodon aureofasciatus and
      Chaetodon lunulatus) that were restricted to feeding upon either bleached or
      healthy coral tissue of Acropora spathulata or Pocillopora damicornis. Coral
      condition (bleached vs. unbleached) had no significant effects on changes in
      total length or weight over a 23-day period. Likewise, in a habitat choice
      experiment, juvenile butterflyfishes did not discriminate between healthy and
      bleached corals, but actively avoided using recently dead colonies. These results
      indicate that juvenile coral-feeding fishes are relatively robust to short term
      effects of bleaching events, provided that the corals do recover. 

PMID- 24680107
TI  - Histopathological survey of potential biomarkers for the assessment of
      contaminant related biological effects in species of fish and shellfish collected
      from Kuwait Bay, Arabian Gulf.
AB  - The marine environment in Kuwait is dominated by Kuwait Bay, a shallow,
      depositional habitat vital for the breeding and propagation of marine organisms.
      The bay receives effluent inputs from industrial centres, ports, sewage outflows
      along with discharges from power and desalination plants. The major classes of
      pollutant discharged into the bay include petroleum hydrocarbons, metals,
      nutrients, cooling water and hyper-saline water. Further, the bay has been
      historically impacted by a deliberate release of oil and contamination with
      ordnance and shipwrecks during the 1991 Gulf war. With an aim to establish an
      integrated pollution effects monitoring programme in Kuwait, this paper describes
      the application of a quality assured approach to conduct a histopathology
      baseline survey in oriental sole (Synaptura orientalis) and the large-toothed
      flounder (Pseudorhombus arsius), which are two potential sentinel flatfish
      species present in the Arabian Gulf. Liver and gonadal histopathology revealed a
      range of pathologies similar to those previously observed in European and
      American pollution effects surveys that utilise flatfish (including pathology
      markers indicative of possible carcinogenesis and endocrine disruption). Further,
      we extended these studies to invertebrates (Jinga prawn, Metapenaeus affinis and
      the grooved tiger prawn, Penaeus semisulcatus) found within the Arabian Gulf.
      Such baseline data is essential before attempts are made to develop integrated
      monitoring programmes that aim to assess the health of fish and shellfish in
      relation to chemical contamination. 

PMID- 24680108
TI  - Holding the baby: early mother-infant contact after childbirth and outcomes.
AB  - AIM: to describe the timing, type and duration of initial infant contact and
      associated demographic and clinical factors in addition to investigating the
      impact of early contact on breastfeeding and maternal health and well being after
      birth. METHOD: data from a recent population survey of women birthing in
      Queensland, Australia were used to describe the nature of the first hold and
      associated demographic characteristics. Initial comparisons, with subsequent
      adjustment for type of birthing facility and mode of childbirth, were used to
      assess associations between timing, type and duration of initial contact and
      outcomes. Further analyses were conducted to investigate a dose-response
      relationship between duration of first contact and outcomes. FINDINGS: women who
      had an unassisted vaginal birth held their infant sooner, and for longer than
      women who had an assisted vaginal birth or caesarean and were more satisfied with
      their early contact. Multivariate models showed a number of demographic and
      clinical interventions contributing to timing, duration and type of first contact
      with type of birthing facility (public/private), area of residence, and assisted
      birth as prominent factors. For women who had a vaginal birth; early, skin-to
      skin, and longer duration of initial contact were associated with high rates of
      breastfeeding initiation and breastfeeding at discharge, but not breastfeeding at
      13 weeks. Some aspects of early contact were associated with improved maternal
      well being. However, these associations were not found for women who had a
      caesarean birth. With longer durations of first contact, a dose-response effect
      was found for breastfeeding. CONCLUSION: results of the study provide a
      description of current practice in Queensland, Australia and factors impacting on
      early contact. For vaginal births, findings add to the evidence in support of
      early skin-to-skin contact for an extended period. It is suggested that all
      research in this area should consider the effects of early contact separately for
      women having vaginal and caesarean births. IMPLICATIONS FOR PRACTICE: care
      providers should consider extending the period of early contact in routine care
      following vaginal birth and explore the way in which women having a caesarean
      birth might be better supported in benefitting from early contact with their
      infant.

PMID- 24680109
TI  - [Delays for lung cancer treatment: performance with respect to timeliness and
      increase of investigations].

PMID- 24680110
TI  - [Tobacco in words: a semantic and historical journey within total independence].

PMID- 24680111
TI  - [An analysis of treatment delays of thoracic cancers: a prospective study].
AB  - INTRODUCTION: Lung cancer is the main cause of cancer death in France. The
      diagnosis is often late and the delay between the onset of symptoms and
      management is considered an aggravating factor. MATERIAL AND METHODS: Our
      prospective study collected the dates of the start of management of 139
      consecutive patients receiving first line treatment for thoracic cancer in our
      hospital between November 2008 and May 2009. The aim of this study was to
      evaluate the delays in medical or surgical treatments in patients with thoracic
      cancer and to determine the cause of these delays. RESULTS: The median delay
      between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays
      were significantly shorter in the late stages and in small cell cancer (P=0.001).
      There was a tendency for shorter delays in women and for longer delays in older
      patients. CONCLUSION: Evaluation of the delays in treatment, particularly in the
      early stages, is part of the quality control of management of these diseases.

PMID- 24680112
TI  - [Treatment and prognosis of advanced stage non-small-cell lung cancer].
AB  - INTRODUCTION: Lung cancer is the main cause of death from cancer in both men and
      women worldwide. In 70 to 80% of cases, the diagnosis is made at an advanced
      stage. Although the management of non-small-cell lung cancer (NSCLC) has
      continued to improve over the last 5 years, the prognosis remains poor with a 5
      year survival rate of about 16%. The aim of this study was to evaluate the
      management of locally advanced or metastatic NSCLC in our patients and to analyze
      overall survival (OS) and prognostic factors at these stages. MATERIALS AND
      METHODS: A retrospective study, including cases of locally advanced and
      metastatic NSCLC diagnosed in our department between 2008 and 2011. RESULTS: We
      included 150 patients with a mean age of 60.2 years. The cancer was at stage IIIA
      in 21% of cases, IIIB in 14% of cases and IV in 65% of cases. Thoracic surgery
      was performed in 5 patients; 61.4% of patients received chemotherapy and chemo
      radiotherapy was given in 21% of patients. Overall survival was 6 months. Better
      survival was observed in patients aged less than 60 years, having better
      performance status (PS), having no metastatic mediastinal lymph nodes and
      patients who received specific anti-tumor treatment. CONCLUSIONS: The prognostic
      factors in locally advanced and metastatic NSCLC in our patients were: age, PS,
      status of mediastinal lymph nodes at diagnosis and treatment. These factors
      should be considered by physicians when treating patients with advanced stage
      NSCLC.

PMID- 24680113
TI  - [Identification of occupational exposure in thoracic oncology: a Belgian
      experience].
AB  - INTRODUCTION: In Belgium in 2008, the body responsible for compensating and
      indemnifying victims of occupational diseases recognized 62 cases of lung cancer,
      although 702 cases were expected. There is an "underreporting" of occupational
      lung cancer. This study aimed to assess the number of cases of occupational lung
      cancer in a Belgian hospital specialized in oncology. PATIENT AND METHOD: From
      September 1st, 2009 to January 31st, 2011, each new patient with lung cancer has
      been directed to a consultation identifying occupational exposure to lung
      carcinogens. RESULTS: Among 81 occupational histories, 28 patients (35%) were
      found to have been definitely or probably exposed to one or more lung carcinogens
      (known or suspected). These patients were all male, mostly blue collar workers.
      Thirteen compensation claims for occupational disease have been introduced: nine
      recognized, one rejected and three pending. CONCLUSION: This study demonstrates
      the importance of a physician trained in occupational diseases within a thoracic
      oncology unit in reducing the "underreporting" of occupational lung cancer and
      thus providing the victims with the compensation to which they are legitimately
      due.

PMID- 24680114
TI  - [Anxiety-depressive disorders and bronchiectasis].
AB  - INTRODUCTION: Bronchiectasis is a chronic lung disease that may be associated
      with anxiety-depressive disorders affecting the quality of life of patients.
      Detecting these anxiety-depressive disorders may be necessary in the support and
      overall management of a patient with bronchiectasis. AIMS: To evaluate the
      prevalence of anxiety and depression in patients with bronchiectasis and to
      investigate the possible correlation between the severity of the disease and the
      importance of these psychological disorders. PATIENTS AND METHODS: This was a
      prospective study that included 53 patients with stable bronchiectasis and
      without other comorbidities. All the patients underwent a complete clinical
      examination, spirometry and chest computed tomography. All the 53 patients
      responded to the Hospital Anxiety and Depression Scale (HAD) questionnaire.
      RESULTS: Anxiety was present in 22.7% of patients and depression in 20.8%.
      Subjects who had an anxiety disorder had symptoms primarily of dyspnoea
      (P=0.001), a low FEV (P=0.04) and respiratory failure at a stage requiring home
      oxygen therapy (P=0.009). A similar comparison of patients with and without
      depressive disorder again found a high prevalence of dyspnea (P=0.003), a low FEV
      (P=0.04), and chronic respiratory failure in the depressive patients. CONCLUSION:
      Symptoms of depression and anxiety are common in patients with bronchiectasis and
      appear to be associated with dyspnoea. Early detection is necessary in the
      context of the overall management of these patients.

PMID- 24680115
TI  - [Perceptions of cystic fibrosis patients, patient relatives and physicians:
      barriers or motivations to lung transplantation].
AB  - INTRODUCTION: The aims of this study are to describe qualitatively the
      perceptions of three groups involved in the cystic fibrosis transplant decision,
      looking for similarities and differences between groups, and to identify those
      that act as motivations or barriers to transplantation. METHODS: Thirty patients,
      26 patient relatives and 27 physicians were interviewed, and concept maps were
      constructed from those interviews. Their degree of transplant acceptance at the
      time of the interview was measured. RESULTS: There were motivations and barriers
      in the pre-, peri- and post-transplant period. Analysis revealed similar
      perceptions regarding the risks and benefits of transplantation, but also
      different perceptions in the specific concerns of each group. Patients and
      patient relatives expressed many questions and fears in their concept maps, and
      physicians expressed difficulties. CONCLUSIONS: This study highlights the value
      of better understanding the perceptions of patients, relatives and physicians, in
      order to remove some of the barriers to transplantation. It also demonstrates the
      benefits of education and support activities for patients and patient relatives
      prior to transplantation, and continuing education and supervision for
      physicians.

PMID- 24680116
TI  - [Smoking behavior among nursing students in Sousse, Tunisia: a preliminary
      study].
AB  - INTRODUCTION: Smoking is an entirely preventable, man-made, epidemic. It is a
      major, worldwide, public health problem whose social costs are very high. Health
      care workers have an important role to play in tobacco control. We conducted a
      study among nursing students to examine their smoking behavior, their attitudes
      towards smoking, and their participation in prevention. METHODS: This
      descriptive, transverse study was conducted in March 2011 during which an
      anonymous self-completion questionnaire was administered to nursing students.
      RESULTS: The study included 150 students aged between 18 and 25 years with a sex
      ratio of 1:3. The prevalence of smoking was 32.6%. Male students began smoking at
      an earlier age (16.5+/-2.3 years vs 18.9+/-1.1 years). The main initiating
      factors were stress (55%), pleasure (46.9%) and peer influence (36.5%). The
      Fagerstrom score showed a high level of dependency in 26.5% of smokers. More than
      75% of student smokers have tried to quit. Most of the students surveyed (93%)
      think that health care workers should set a good example by not smoking and 91%
      of them think they should help others quit smoking. CONCLUSION: Health care
      workers should be well informed about the harmful effects of tobacco. They should
      be convinced of the need for their participation in smoking prevention and the
      fight against this medico-social scourge. It is essential that their training
      prepares them for this task and that their environment helps them fulfill their
      responsibility.

PMID- 24680117
TI  - [Severe hypercalcemia revealing sarcoidosis precipitated by etanercept].
AB  - INTRODUCTION: The principal secondary effects of anti-TNF alpha therapy are now
      well understood, particularly the risk of opportunistic infections. Other
      paradoxical effects have been described much more occasionally such as the
      developement of sarcoid-like granulomatous reactions. CASE REPORT: We report here
      the case of a woman of 39 years treated for severe rheumatoid arthritis for five
      years with etanercept. She was admitted to hospital as an emergency with vomiting
      and diffuse abdominal pain. Investigations revealed severe hypercalcaemia and
      acute renal failure. After correction of the metabolic disturbances with
      rehydration and biphosphonates, CT scanning of the abdomen, pelvis and thorax
      showed bilateral interstitial infiltration and splenomegaly. The diagnosis of
      sarcoidosis was confirmed by endoscopic bronchial biopsies. Progress was
      satisfactory following withdrawal of the etanercept and corticosteroid therapy in
      reducing dosage. CONCLUSION: The risk of induced sarcoidosis should be understood
      in patients receiving anti-TNF therapy and should be considered in cases of
      hypercalcaemia and/or splenomegaly.

PMID- 24680118
TI  - [Bronchioloalveolar carcinoma: an exceptional cause of diffuse lung disease in a
      patient with acute myeloid leukemia].
AB  - INTRODUCTION: Bronchiolo-alveolar carcinoma is a primary pulmonary adenocarcinoma
      developing in the terminal respiratory unit. CASE REPORT: An 84-year-old non
      smoker woman with a history of untreated acute myeloid leukaemia was referred to
      the intensive care unit for pneumonia and acute respiratory failure. The patient
      reported dyspnoea and a productive cough for 3 months, treated by antibiotics and
      steroids without improvement. Thoracic CT-scan showed alveolar condensations and
      multiple nodular lesions. All microbiological samples were negative and the
      evolution was fatal within 72 hours despite empirical antibiotic therapy and
      noninvasive ventilation. Post-mortem lung biopsies gave a diagnosis of mucinous
      and non-mucinous bronchiolo-alveolar carcinoma with typical lepidic growth
      pattern of tumor cells and discrete septal thickening but no fibrosis,
      inflammation or local invasion. CONCLUSION: Bronchiolo-alveolar carcinoma is an
      alternative diagnosis in alveolar condensations associated with pulmonary nodules
      even in a patient with immunosupression. Early diagnosis allows effective
      treatment in some cases.

PMID- 24680119
TI  - [French Pulmonary Medicine Society. Guidelines for clinical practice. Management
      of COPD. Update 2012: Pulmonary function tests. Full length text].

PMID- 24680120
TI  - Characteristics and outcome of enhancing foci followed on breast MRI with
      management implications.
AB  - AIM: To evaluate the risk of cancer of an enhancing focus identified at breast
      magnetic resonance imaging (MRI) by determining the positive predictive value
      (PPV) associated with specific characteristics of an enhancing focus. MATERIALS
      AND METHODS: Retrospective, institutional review board-approved review of the
      database identified 111 consecutive patients who underwent short-term follow-up
      of 136 enhancing foci in 2008. Kinetic analysis (delayed enhancement pattern) and
      other characteristics, such as interval change and T2 signal intensity, were
      evaluated to calculate the PPV for malignancy. RESULTS: The overall malignancy
      rate of an enhancing focus was 2.9% [4/136, 95% confidence interval (CI): 0.9
      7.6%]. Kinetic analysis showed no statistical difference in PPV between foci with
      washout enhancement [5.1% (2/39)] versus persistent enhancement [3.2% (2/62);
      Fisher's exact test, p = 0.6180]. PPV of a T2 hypointense focus was 8.7% (4/46);
      PPV of a new focus was 13.6% (3/22); PPV of an enlarging focus was 6.7%, (1/15).
      The combination of a focus being new and T2 hypointense had the highest PPV for
      malignancy (27.2%, 3/11, 95% CI: 9.2-57.1%). CONCLUSION: Kinetic analysis was not
      specific for malignancy and should not be used solely to guide management. A new
      enhancing focus with T2 hypointensity had a high PPV for malignancy and may
      warrant immediate biopsy.

PMID- 24680121
TI  - Re: the prevalence of incidentally detected adrenal enlargement on CT. A reply.

PMID- 24680122
TI  - Parturition to resumption of ovarian cyclicity: comparative aspects of beef and
      dairy cows.
AB  - There is a variable anoestrous period following parturition in the cow.
      Follicular growth generally resumes within 7 to 10 days in the majority of cows
      associated with a transient FSH rise that occurs within 3 to 5 days of
      parturition. Dairy cows that are not nutritionally stressed generally ovulate
      their first postpartum dominant follicle (~15 days), whereas beef suckler cows in
      good body condition normally have a mean of 3.2+/-0.2 dominant follicles (~30
      days) to first ovulation; moreover, beef cows in poor body condition have a mean
      of 10.6+/-1.2 dominant follicles (~70 to 100 days) to first ovulation. The lack
      of ovulation of dominant follicles during the postpartum period is associated
      with infrequent LH pulses, with both maternal-offspring bonding and low body
      condition score (BCS) at calving being implicated as the predominant causes of
      delayed resumption of cyclicity in nursed beef cows. In dairy cows, the normal
      pattern of early resumption of ovulation may be delayed in high-yielding Holstein
      type cows generally owing to the effects of severe negative energy balance,
      dystocia, retained placental membranes and uterine infections. First ovulation,
      in both dairy and beef cows, is generally silent (i.e., no behavioural oestrus)
      and followed by a short inter-ovulatory interval (>70%). The key to optimizing
      the resumption of ovulation in both beef and dairy cows is appropriate pre
      calving nutrition and management so that cows calve down in optimal body
      condition (BCS; 2.75 to 3.0) with postpartum body condition loss restricted to
      <0.5 BCS units. 

PMID- 24680123
TI  - Current and future directions of DNA in wildlife forensic science.
AB  - Wildlife forensic science may not have attained the profile of human
      identification, yet the scale of criminal activity related to wildlife is
      extensive by any measure. Service delivery in the arena of wildlife forensic
      science is often ad hoc, unco-ordinated and unregulated, yet many of those
      currently dedicated to wildlife conservation and the protection of endangered
      species are striving to ensure that the highest standards are met. The genetic
      markers and software used to evaluate data in wildlife forensic science are more
      varied than those in human forensic identification and are rarely standardised
      between species. The time and resources required to characterise and validate
      each genetic maker is considerable and in some cases prohibitive. Further, issues
      are regularly encountered in the construction of allelic databases and allelic
      ladders; essential in human identification studies, but also applicable to
      wildlife criminal investigations. Accreditation and certification are essential
      in human identification and are currently being strived for in the forensic
      wildlife community. Examples are provided as to how best practice can be
      demonstrated in all areas of wildlife crime analysis and ensure that this field
      of forensic science gains and maintains the respect it deserves. This review is
      aimed at those conducting human identification to illustrate how research
      concepts in wildlife forensic science can be used in the criminal justice system,
      as well as describing the real importance of this type of forensic analysis. 

PMID- 24680124
TI  - SNP variation with latitude: Analysis of the SNPforID 52-plex markers in north,
      mid-region and south Chilean populations.
AB  - Chile is a disproportionately long and narrow country defined by the southern
      Andes and Pacific coastline where a level of genetic sub-structure resulting from
      distances of several thousand kilometers might be expected across the most
      distantly separated regions. Although STR databases created for the Chilean Legal
      Medical Service indicate an absence of sub-structure, such a characteristic
      requires further exploration when introducing additional forensic markers.
      Notably, Single Nucleotide Polymorphisms (SNPs) have a much lower mutation rate
      than STRs and can show more stable distributions of genetic variation if
      population movement is restricted. In this study we evaluated 451 Chilean urban
      samples from the North, North-Central, Central, South-Central and South regions
      of Chile for the 52 SNPs of the SNPforID forensic identification panel to explore
      the underlying genetic structure of Chilean populations. Results reveal similar
      genetic distances between groups suggesting a single SNP database for the whole
      of Chile is appropriate. To further understand the genetic composition of Chilean
      populations that comprise the bulk of individuals with both European and Native
      American ancestries, ancestral membership proportions were evaluated and pairwise
      comparisons to other American populations were made. 

PMID- 24680125
TI  - DNA extraction for short tandem repeat typing from mixed samples using anti-human
      leukocyte CD45 and ABO blood group antibodies.
AB  - DNA testing from mixed cell samples can be difficult to use successfully in
      criminal investigations. Here, we present a method for the extraction of DNA from
      mixed bloodstains involving plural contributors, after antibody-microbead
      captured cell separation. This method, together with the multiplex short tandem
      repeat typing presented, has proven highly successful in the recovery of DNA
      profiles corresponding to the ABO blood type. Methodological steps include
      magnetic separation using leukocyte specific CD45 antibody-coated microbeads and
      centrifugal separation of leukocyte agglutination by ABO antibody. The detection
      results of variable mixed ratio showed that the target DNA was detected
      accurately as low as 1:512 mixed ratio, regardless of the large amount of the
      background DNA present. The method presented here is applicable to PCR-based
      identification for various kinds of mixed samples. 

PMID- 24680126
TI  - Comparing six commercial autosomal STR kits in a large Dutch population sample.
AB  - Regularly, STR results obtained with different PCR amplification kits are
      compared, for instance with old cases, when revisiting cold cases or when
      addressing cross-border crimes. It is known that differences in primer design for
      the same loci in different kits may give rise to null alleles or shifted alleles.
      In this study, the genotyping results of 2085 Dutch male samples were compared
      for six autosomal STR kits (Promega's PowerPlex((r)) 16, ESX-16 and ESI-17
      Systems, Qiagen's Investigator((r)) ESSplex Kit and Applied Biosystems'
      AmpFlSTR((r)) Identifiler and NGM PCR Amplification Kits). A total of 19
      discordant autosomal genotyping results were obtained that were examined by
      sequence analysis using Roche-454 next generation sequencing and/or Sanger
      sequencing. A further 25 discordances were found and sequenced for the Amelogenin
      locus. The 24 samples showing the same primer binding site mutation at the
      Amelogenin locus were subjected to X-STR analysis in order to assess whether they
      could share a common origin, which appeared not to be the case. Based on the
      sequencing results, we set the final genotypes and determined the allele
      frequencies of 23 autosomal STRs for the Dutch reference database. 

PMID- 24680128
TI  - Convenient and selective "off-on" detection nitric oxide in solution and thin
      film with quinoline based fluorescence sensor.
AB  - Quinoline based fluorescence sensor (1) was synthesized and characterized with
      mass spectra (MS), ((1))H nuclear magnetic resonance (((1))H NMR) spectrometer,
      elemental analyses, and infrared (IR) spectra. Following fluorescence experiments
      demonstrate 1 can coordinate with copper ions, and lead to fluorescence
      completely quenched. The 1-copper complex was used as a "turn-on" fluorescence
      biosensor to convenient and highly effective detect nitric oxide (NO) over other
      radicals in solution and PCL-based thin film. The finding would enable the
      quinoline based fluorescence probe to be an "off-on" convenient NO fluorescence
      probe. 

PMID- 24680127
TI  - The risk of developing a second primary cancer in melanoma patients: a
      comprehensive review of the literature and meta-analysis.
AB  - The number of cutaneous melanoma survivors has been increasing for years due to
      improvements in early diagnosis and subsequent prolonged survival. These patients
      are at increased risk of developing a second melanoma and a second primary
      malignancy (SPM) at other sites as well. We performed a review of scientific
      literature and meta-analysis to evaluate the risk of developing a SPM (other than
      melanoma) among melanoma patients. Twenty-three independent papers and over
      350,000 melanoma patients were included. Risk of cancer among melanoma survivors
      was increased overall (1.57, 95% CI 1.29-1.90) and at several sites: bone (2.09,
      95% CI 1.08-4.05), non-melanoma skin cancer (4.01, 95% CI 1.81-8.87), soft tissue
      (6.80, 95% CI 1.29-35.98), colon-rectum (1.12, 95% CI 1.00-1.25), female breast
      (1.14, 95% CI 1.07-1.22), kidney (1.34, 95% CI 1.23-1.45), prostate (1.25, 95% CI
      1.13-1.37) and non-Hodgkin lymphoma (1.37, 95% CI 1.22-1.54). The overall risk of
      SPM showed a tendency to decrease as the time from melanoma diagnosis lengthened.
      Most of our findings may be explained by the tendency of some exposures, which
      are risk factors for different tumors, to occur simultaneously in the same
      individuals. These results suggest primary and secondary cancer prevention
      counselling for melanoma survivors. 

PMID- 24680129
TI  - How to overcome male infertility after 40: Influence of paternal age on
      fertility.
AB  - The recent trend toward delayed parenthood raises major safety concerns because
      of the adverse effects of aging on couple fertility. Studies have demonstrated
      that aging clearly affects female fertility, but can also affect male fertility.
      Although several theories have been proposed, the exact mechanisms responsible
      for the observed age-related decline in male fertility remain to be elucidated.
      It has been shown that advanced paternal age (PA) is associated with reduced
      semen volume as well as, reduced sperm count, motility and morphology. Recent
      studies have also reported that paternal aging is associated with a significant
      increase in the prevalence of both genomic and epigenomic sperm defects. In the
      context of natural and intrauterine insemination (IUI) conception, advanced
      paternal age has been associated with lower pregnancy rates and increased rates
      of spontaneous abortion (independent of maternal age). In IVF and oocyte donation
      programs, a significant decrease in late blastocyst development has been seen in
      those cycles using spermatozoa of men older than 55. However, no significant
      relationship between paternal age and IVF or ICSI pregnancy rates has been
      observed. Although there are no treatments that can fully restore the age-related
      decline in male fertility, various measures have been shown to optimize male
      fertility potential. Specific therapies (e.g. varicocelectomy) and lifestyle
      changes (e.g. dietary antioxidant supplements) may help minimize some of the age
      related deleterious effects on spermatogenesis, such as, oxidative stress and
      endocrine abnormalities.

PMID- 24680131
TI  - TEE images of inferior vena cava conduit thrombosis following extracardiac total
      cavopulmonary anastomosis.

PMID- 24680130
TI  - Type of anesthesia and postoperative delirium after vascular surgery.
AB  - OBJECTIVE: The purpose of this study was to investigate the association between
      general (GA), regional (RA), and local (LA) anesthetic techniques with respect to
      the development of delirium after vascular surgery. The authors hypothesized that
      patients undergoing GA for vascular surgery would have a higher incidence of
      postoperative delirium. The role of LA with respect to postoperative delirium in
      vascular surgery patients previously has not been reported. DESIGN: Retrospective
      review. SETTING: Tertiary referral center, university hospital. PARTICIPANTS: 500
      patients undergoing vascular surgical procedures. INTERVENTIONS: Based on the
      chosen anesthetic technique, all patients were divided into GA, RA, and LA
      groups, respectively. Exclusion criteria were patients with preoperative dementia
      or abnormal level of consciousness, patients undergoing open abdominal aneurysm
      repair surgery, and patients undergoing carotid endarterectomy. All anesthetic
      techniques were conducted according to routine institutional practices. Patients
      in both the RA and LA groups received intravenous sedation. MEASUREMENTS AND MAIN
      RESULTS: Three hundred ninety-six (79%) patients received GA, 73 (15%) RA, and 31
      (6%) LA. The overall incidence of delirium was 19.4% and rates were similar among
      the 3 groups, with 73 (18.4%) patients in the GA group, 17 (23.2%) in the RA
      group, and 7 (22.5%) in the LA group (p = 0.56). Patients in the LA group were
      more likely to have emergency surgery and also had a higher incidence of previous
      cerebrovascular accidents or transient ischemic attacks. There was no significant
      difference with respect to either onset or duration of delirium among the 3
      groups. Median length of hospital stay and in-hospital mortality were similar
      among the 3 groups. CONCLUSIONS: Delirium rates after vascular surgery were
      similar with local, regional, or general anesthesia techniques. The presence of
      risk factors for the development of postoperative delirium should not influence
      the type of anesthesia provided.

PMID- 24680132
TI  - Risk factors of postoperative acute kidney injury in patients undergoing
      esophageal cancer surgery.
AB  - OBJECTIVE: The purpose of this study was to identify perioperative risk factors
      for postoperative acute kidney injury (AKI) in patients undergoing esophageal
      cancer surgery. DESIGN: A retrospective analysis of the prospectively collected
      medical data. SETTING: A tertiary care university hospital. PARTICIPANTS: All
      consecutive adult patients (n=595) who underwent elective esophageal surgery for
      cancer between January 2005 and April 2012. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: AKI was defined by the AKI Network criteria based on serum
      creatinine changes within the first 48 hours after esophageal cancer surgery. The
      relationship between perioperative variables and AKI was evaluated using
      multivariate logistic regression. Postoperative AKI developed in 210 (35.3%)
      patients. Risk factors for AKI were body mass index (odds ratio [OR] 1.07; 95%
      confidence interval [CI] 1.01-1.14), preoperative serum albumin level (OR 0.52;
      95% CI 0.33-0.84), use of angiotensin-converting enzyme inhibitors or angiotensin
      receptor blockers (OR 1.35; 95% CI 1.05-1.75), colloid infusion during surgery
      (OR 1.11; 95% CI 1.06-1.18), and postoperative 2-day C-reactive protein (OR 1.05;
      95% CI 1.01-1.09). Postoperative AKI was associated with prolonged length of
      hospital stay. CONCLUSIONS: Postoperative AKI is common in patients undergoing
      esophageal surgery for cancer. Closer evaluation and monitoring in patients with
      risk factors for AKI may be warranted.

PMID- 24680133
TI  - Measurement and simulation of Joule heating during treatment of B-16 melanoma
      tumors in mice with nanosecond pulsed electric fields.
AB  - Experimental evidence shows that nanosecond pulsed electric fields (nsPEF)
      trigger apoptosis in skin tumors. We have postulated that the energy delivered by
      nsPEF is insufficient to impart significant heating to the treated tissue. Here
      we use both direct measurements and theoretical modeling of the Joule heating in
      order to validate this assumption. For the temperature measurement, thermo
      sensitive liquid crystals (TLC) were used to determine the surface temperature
      while a micro-thermocouple (made from 30 MUm wires) was used for measuring the
      temperature inside the tissue. The calculation of the temperature distribution
      used an asymptotic approach with the repeated calculation of the electric field,
      Joule heating and heat transfer, and the subsequent readjustment of the
      electrical tissue conductivity. This yields a temperature distribution both in
      space and time. It can be shown that for the measured increase in temperature an
      unexpectedly high electrical conductivity of the tissue would be required, which
      was indeed found by using voltage and current monitoring during the experiment.
      Using impedance measurements within t(after)=50 MUs after the pulse revealed a
      fast decline of the high conductivity state when the electric field ceases. The
      experimentally measured high conductance of a skin fold (mouse) between plate
      electrodes was about 5 times higher than those of the maximally expected
      conductance due to fully electroporated membrane structures
      (G(max)/G(electroporated))~5. Fully electroporated membrane structure assumes
      that 100% of the membranes are conductive which is estimated from an impedance
      measurement at 10 MHz where membranes are capacitively shorted. Since the
      temperature rise in B-16 mouse melanoma tumors due to equally spaced (Deltat=2 s)
      300 ns-pulses with E=40 kV/cm usually does not exceed DeltaTau=3 K at all parts
      of the skin fold between the electrodes, a hyperthermic effect on the tissue can
      be excluded.

PMID- 24680134
TI  - Post-tonsillectomy complications in children less than three years of age: a case
      control study.
AB  - OBJECTIVES: To assess the need for post-tonsillectomy admission in children under
      the age of three years. DESIGN: A retrospective case-control study. METHOD:
      Medical records of 127 children under the age of three years who underwent
      tonsillectomy with or without adenoidectomy were reviewed for complications and
      compared to 127 gender-matched controls between three to four years of age.
      RESULTS: Overall complication rate in the study group was 9.4% (12 of 127). Early
      complications (3.1%) were respiratory related, while late complications (6.3%)
      were due to dehydration and hemorrhage. Comparable complication rate was observed
      in the control group (8.7%, P>0.05); early complication rate of 3.1% and late
      complication rate of 5.5% was ascertained. Similar types of complications
      occurred in the control group. CONCLUSIONS: Post-tonsillectomy complication rates
      were low and no significant difference was observed between the study and control
      groups. This suggests that postoperative admission for children younger than
      three years of age may not be necessary in all cases.

PMID- 24680135
TI  - Otogenic lateral sinus thrombosis: case series and controversies.
AB  - OBJECTIVES: The aim of this study is to (1) report the clinical presentation,
      treatment, and sequelae in a series of pediatric patients with otogenic lateral
      sinus thrombosis and (2) to review the most controversial aspects of management
      of this rare intracranial complication of otitis media. METHODS: Retrospective
      chart review of inpatients treated for central venous thrombosis at a tertiary
      care facility between 1996 and 2012. RESULTS: Five pediatric patients (four male,
      one female) were identified with otogenic lateral sinus thrombosis. Age at
      presentation ranged from 13 months to 15 years. All underwent a surgical
      procedure, ranging from a simple myringotomy with tympanostomy tube placement to
      tympanomastoidectomy and internal jugular vein ligation or craniotomy. Three were
      anticoagulated with unfractionated heparin with subsequent transition to low
      molecular weight heparin of variable duration. One patient developed a non-life
      threatening intracranial hemorrhage while on long-term anticoagulation. Follow-up
      imaging, when available, did not directly correlate complete thrombus resolution
      with use of anticoagulation or with persistent symptoms. CONCLUSIONS: Otogenic
      lateral sinus thrombosis is a rare intracranial complication of otitis media with
      significantly reduced morbidity and mortality in the modern era of antibiotic
      treatment, surgical intervention, and anticoagulation therapy. Due to the rarity
      of this condition today, the recommended extent of surgical intervention and need
      for routine anticoagulation are unclear, and requires further data to determine
      definitively.

PMID- 24680136
TI  - Subcutaneous emphysema--beyond the pneumoperitoneum.
AB  - BACKGROUND: Subcutaneous emphysema and gas extravasation outside of the
      peritoneal cavity during laparoscopy has consequences. Knowledge of the
      circumstances that increase the potential for subcutaneous emphysema is necessary
      for safe laparoscopy. METHODS: A literature review and a PubMed search are the
      basis for this review. CONCLUSIONS: The known risk factors leading to
      subcutaneous emphysema during laparoscopy are multiple attempts at abdominal
      entry, improper cannula placement, loose fitting cannula/skin and fascial entry
      points, use of >5 cannulas, use of cannulas as fulcrums, torque of the
      laparoscope, increased intra-abdominal pressure, procedures lasting >3.5 hours,
      and attention to details. New additional risk factors acting as direct factors
      leading to subcutaneous emphysema risk and occurrence are total gas volume, gas
      flow rate, valveless trocar systems, and robotic fulcrum forces. Recognizing this
      spectrum of factors that leads to subcutaneous emphysema will yield greater
      patient safety during laparoscopic procedures.

PMID- 24680137
TI  - Hostile Abdomen Index Risk stratification and laparoscopic complications.
AB  - BACKGROUND: Common life-threatening complications associated with laparoscopy,
      including bleeding and inadvertent enterotomy, are described in the literature.
      We investigated the application of the Hostile Abdomen Index related to these
      complications. We hypothesize that the preoperative score may guide a surgeon in
      risk stratification. METHODS: We used data from Monmouth Medical Center morbidity
      and mortality conferences and reviewed bleeding and enterotomy complications in
      laparoscopic abdominal surgery. Complications were tracked using the Hostile
      Abdomen Index compared between 2 periods: published early experience with
      laparoscopic surgery (1998-2003) and unpublished late experience (2004-2010). The
      index ascribes a number (1-4) before a laparoscope is inserted and another number
      (1-4) after the laparoscope is inserted into the abdomen. RESULTS: From 1998 to
      2010, 43 patients had bleeding complications (0.45%) and 28 had inadvertent
      enterotomies (0.29%). There was no difference in bleeding between the early and
      late experiences. Enterotomy complications decreased in the late experience (P <
      .001). Our rescue success was 97.2% over 13 years. Those laparoscopic cases with
      high preoperative scores (3-4) had a higher rate of conversion to open
      procedures. CONCLUSIONS: The Hostile Abdomen Index can be used to track 2
      potentially life-threatening laparoscopic complications. The index score has been
      explained to our surgeons on numerous occasions. A higher chance of bleeding and
      enterotomy or risk stratification correlates with a preoperative 3 or 4 score and
      may lead to a more cautious approach toward initial laparotomy or earlier
      conversion.

PMID- 24680138
TI  - Colonoscopic perforation management by laparoendoscopy: an algorithm.
AB  - BACKGROUND AND OBJECTIVES: The role of laparoscopy in the management of
      iatrogenic colonoscopic injuries has increased with surgeons becoming facile with
      minimally invasive methods. However, with a limited number of reported cases of
      successful laparoscopic repair, the exact role of this modality is still being
      defined. Drawing from previous literature and our own experiences, we have
      formulated a simple algorithm that has helped us treat colonoscopic perforations.
      METHODS: A retrospective review was undertaken of patients treated for
      colonoscopic perforations since the algorithm's introduction. For each patient,
      initial clinical assessment, management, and postoperative recovery were
      carefully documented. A Medline search was performed, incorporating the following
      search words: colonoscopy, perforation, and laparoscopy. Twenty-three articles
      involving 106 patients were identified and reviewed. RESULTS: Between May 2009
      and August 2012, 7 consecutive patients with colonoscopic perforations were
      managed by 2 surgeons using the algorithm. There were no complications and no
      deaths, with a mean length of stay of 4.43 days (range, 2-7 days). Of the 7
      patients, 6 required surgery. A single patient was managed conservatively and
      later underwent an elective colon resection. CONCLUSIONS: Traditionally,
      laparotomy was the preferred method for treating colonoscopic perforations. Our
      initial experience reinforces previous views that laparoendoscopic surgery is a
      safe and effective alternative to traditional surgery for managing this
      complication. We have formulated a simple algorithm that we have found helpful
      for surgeons considering a laparoscopic approach to managing this condition.

PMID- 24680139
TI  - Comparison of laparoscopic versus open approach to gastrostomy tubes.
AB  - BACKGROUND AND OBJECTIVES: Gastrostomy tube insertion for enteral access may be
      performed through laparotomy (open) or through the laparoscopic approach. This
      study's purpose is to compare outcomes of these different approaches. METHODS: A
      retrospective chart review of all patients (age >18 years) who underwent
      insertion of a gastrostomy tube as a single elective procedure between 2004 and
      2012 was performed. Primary end points included postoperative overall and tube
      related morbidity, tube revision rates, and operative time. RESULTS: During the
      study period, 71 patients had a gastrostomy tube inserted via either the open (n
      46) or the laparoscopic (n 25) approach. Preoperative variables including age,
      gender, body mass index, albumin, and American Society of Anesthesiologists score
      were statistically comparable between groups. There was no difference in rates of
      previous upper abdominal surgery (24% vs 26%, P = .590) or gastric surgery (12%
      vs 13%, P = .720) in the laparoscopic and open groups, respectively. Previous
      percutaneous endoscopic gastrostomy tube insertion rates were higher in the
      laparoscopic group (32% vs 6.5%, P = .005). Operative time was significantly
      longer in the laparoscopic group (76.8 +/- 7 vs 55.8 +/- 3, P = .003) but was not
      affected by previous abdominal surgery or higher body mass index. Overall
      morbidity, tube-related morbidity, and tube revision rates were similar between
      groups. However, there was a trend toward increased major complication rates in
      the open group (6.5% vs 0%, P = .190). CONCLUSION: Laparoscopic gastrostomy tube
      insertion is safe and feasible, even in patients who have had prior upper
      abdominal surgery. Patients with a prolonged prognosis, obesity, and intact
      neurologic capacity may benefit the most from this approach.

PMID- 24680140
TI  - Single-port laparoscopic parastomal hernia repair with modified sugarbaker
      technique.
AB  - INTRODUCTION: Laparoscopic parastomal hernia repair with modified Sugarbaker
      technique has become increasingly the operation of choice because of its low
      recurrence rates. This study aimed to assess feasibility, safety, and efficiency
      of performing the same operation with single-incision laparoscopic surgery.
      MATERIALS AND METHODS: All patients referred from March 2010 to February 2013
      were considered for single-port laparoscopic repair with modified Sugarbaker
      technique. A SILS port (Covidien, Norwalk, Connecticut, USA) was used together
      with conventional straight dissecting instruments and a 5.5- mm/52-cm/30 degrees 
      laparoscope. Important technical aspects include modified dissection techniques,
      namely, "inline" and "chopsticks" to overcome loss of triangulation, insertion of
      a urinary catheter into an ostomy for ostomy limb identification, safe
      adhesiolysis by avoiding electocautery, saline -jet dissection to demarcate
      tissue planes, dissection of an entire laparotomy scar to expose incidental
      incisional hernias, adequate mobilization of an ostomy limb for lateralization,
      and wide overlapping of defect with antiadhesive mesh. RESULTS: Of 6 patients, 5
      underwent single-port laparoscopic repair, and 1 (whose body mass index [BMI] of
      39.4 kg/m(2) did not permit SILS port placement) underwent multiport repair. Mean
      defect size was 10 cm, and mean mesh size was 660 cm(2) with 4 patients having
      incidental incisional hernias repaired by the same mesh. Mean operation time was
      270 minutes, and mean hospital stay was 4 days. Appliance malfunction ceased
      immediately, and pain associated with parastomal hernia disappeared. There was no
      recurrence with a follow-up of 2 to 36 months. CONCLUSION: Compared with
      multiport repair, single-port laparoscopic parastomal repair with modified
      Sugarbaker technique is safe and efficient, and it may eventually become the
      standard of care.

PMID- 24680141
TI  - Feasibility of a combined percutaneous laparoscopic three-millimeter device.
AB  - BACKGROUND AND OBJECTIVES: Needlescopic 3-mm instruments induce minimal trauma
      and produce excellent cosmetic results. A combination of a 3-mm abdominal wall
      incision and a 5-mm instrument in the abdominal cavity would combine the
      beneficial features of these two different sizes. METHODS: The Percutaneous
      Surgical System (PSS) (Ethicon EndoSurgery, Galway, Ireland) is a new instrument
      consisting of a 3-mm shaft that is introduced percutaneously into the abdominal
      cavity. Through a 5-mm trocar, a loader with a 5-mm attachment such as a Maryland
      dissector is introduced. The attachment is connected to the shaft, and the loader
      is removed from the abdomen. The feasibility of this device was evaluated
      retrospectively in 3 Swedish hospitals between January and September 2012.
      RESULTS: Twenty-eight patients were laparoscopically operated on
      (cholecystectomy, gastric bypass, fundoplication, incisional hernias, and totally
      extraperitoneal repair for inguinal hernia) by use of 1 or 2 PSSs in each
      operation (47 in total). It was feasible to use the PSS in all procedures except
      during the totally extraperitoneal repair procedure because of the limited
      available preperitoneal space. Especially in laparoscopic cholecystectomies, the
      two lateral 5-mm trocars were easily replaced by two 3-mm PSS instruments.
      CONCLUSIONS: The use of the PSS is feasible in a number of laparoscopic
      procedures, where it can replace 5-mm trocars. Randomized controlled trials are
      needed to determine the future role of the PSS versus, for example, needlescopic
      laparoscopy.

PMID- 24680142
TI  - Surgical management of gastrointestinal stromal tumors of the stomach.
AB  - BACKGROUND: Laparoscopy has emerged as the "gold standard" procedure for many
      diseases that require surgical treatment. Our goal was to assess the outcomes of
      laparoscopic vs open partial gastrectomies for the management of gastrointestinal
      stromal tumors of the stomach (gGIST) using a national database. METHODS: Using
      the American College of Surgeons National Surgical Quality Improvement Program
      (ACS NSQIP) database (2006-2009), we identified patients who underwent
      laparoscopic and open partial gastrectomy gGIST. Overall morbidity and mortality
      were assessed. The relationships between anesthesia time, operative duration,
      surgical site infection (SSI), and hospital stay were also examined. Two-sample t
      tests were used. RESULTS: Of 486 patients, 146 (30%) underwent laparoscopic
      resection (LR) and 340 (70%) underwent open resection (OR). Patients who
      underwent LP were older (mean: 65 vs 62 years; P = .062). Patients treated with
      LR experienced shorter anesthesia time (mean: 183 vs 212 minutes; P < .05) and
      shorter operative time (mean: 119 vs 149 minutes; P < .05) compared with those
      who underwent OR. All patients treated with LR had fewer SSIs compared with those
      who underwent OR (0.68% vs 6.7%; P < .001). Patients treated with LR were less
      likely to experience an overall morbidity (mean: 3.9% vs 11.7%; P < .001) or
      mortality (mean: 0.23% vs 0.72%; P < .001) and shorter total hospital stay (mean:
      3.17 vs 7.50 days; P < .001) compared with those who underwent OR. CONCLUSIONS:
      In ACS NSQIP hospitals, laparoscopic resection of gGIST appears to be preferable
      to open surgery. However, prospective studies with large sample sizes comparing
      both surgical approaches with size-matched tumors are strongly suggested.

PMID- 24680143
TI  - Male gender impact on the outcome of laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: Our aim was to assess the impact of male gender on the
      outcomes of laparoscopic cholecystectomy by eliminating associated risk factors
      for conversion. METHODS: A quantitative comparative study was set up on the
      background of our null hypothesis that male gender has no impact on the outcomes
      of laparoscopic cholecystectomy. We performed a retrospective study of 241
      patients and recorded the duration of surgery, length of postoperative hospital
      stay, conversion rate, and procedure-specific complications. Risk factors for
      conversion were excluded. Inferential statistics were applied, and a 2-sided P
      value of < .05 was considered the cutoff point to indicate the amount of evidence
      against the null hypothesis. We used SPSS for Windows, version 12 (IBM, Armonk,
      New York). Parametric data were analyzed with the independent-samples t test, and
      nonparametric data were analyzed with the chi(2) test. RESULTS: A total of 175
      women (72.6%) and 66 men (27.4%) underwent laparoscopic cholecystectomy. The mean
      age was 51.4 +/- 14.8 years for women and 55 +/- 12.7 years for men (P = .08).
      Women had a higher body mass index (28.4 +/- 4.5) than men (26.8 +/- 3.5) (P <
      .005). There were no statistically significant differences in the conversion rate
      and perioperative morbidity rate. The conversion rate was 2.9% for women and 7.5%
      for men (P = .142); the morbidity rate was 10.2% and 12.1%, respectively (P =
      .66). The mean duration of surgery was longer in men, at 67.9 +/- 27.8 minutes,
      than in women, at 56.5 +/- 23.98 minutes (P < .002). Both genders had an equal
      length of postoperative hospital stay, with 1.9 +/- 1.8 days for men and 1.9 +/-
      2.1 days for women (P = .8). CONCLUSIONS: Male gender has no impact on the
      outcomes of laparoscopic cholecystectomy. Gender affects the duration of surgery.
      Larger-scale studies may disclose the factors responsible for variations in the
      operative time.

PMID- 24680144
TI  - Elimination of laparoscopic lens fogging using directional flow of CO2.
AB  - BACKGROUND AND OBJECTIVES: Surgeons constantly struggle with the formation of
      condensation on the lens of a laparoscope, which prolongs procedures and reduces
      visibility of the abdominal cavity. The goal of this project was to build a
      device that would direct a flow of carbon dioxide (CO2) into an open chamber
      surrounding the lens of a laparoscope, acting to keep moisture away from the lens
      and eliminate condensation. METHODS: The device isolates the lens of the
      laparoscope from the humid environment of the intraperitoneal cavity by creating
      a microenvironment of dry CO2. This was accomplished by building a communicating
      sleeve that created an open chamber around the distal 2 to 3 cm of the scope.
      Into this cavity, dry cool CO2 was pumped in from an insufflator so that the path
      of the gas would surround the lens of the scope and escape through a single
      outlet location through which the scope views the intraperitoneal cavity. This
      chamber is proposed to isolate the lens with a high percentage of dry CO2 and low
      humidity. The device was tested in 7 different adverse conditions that were meant
      to challenge the ability of the device to maintain the viewing field with no
      perceptible obstruction. RESULTS: In all of the conditions tested, 25 trials
      total, the device successfully prevented and/or eliminated laparoscopic lens
      fogging. CONCLUSIONS: The device designed for this project points to the
      potential of a simple and effective mechanical method for eliminating
      laparoscopic lens fogging.

PMID- 24680145
TI  - A reproducible ex vivo model for transanal minimally invasive surgery.
AB  - BACKGROUND: Rectal tumors can be excised through a number of minimally invasive
      transanal techniques including transanal excision, transanal endoscopic
      microsurgery, and transanal minimally invasive surgery (TAMIS). Specialty
      training is often required to master the nuances of these approaches. This study
      aimed to create a reproducible transanal excision training model that is suited
      for laparoendoscopic techniques. METHODS: Frozen porcine rectum and anus with
      intact perianal skin were commercially obtained. Thawed specimens were then cut
      to approximately 20 cm in length. The proximal end of the rectum was then everted
      and suction applied to the mucosa to create pseudopolyps of various sizes
      (sessile and pedunculated). Larger pedunculated lesions were made by tying the
      base of the pseudopolyps with 5-0 monofilament sutures to gather more tissue.
      Methylene blue dye was injected submucosally into the lesions to simulate
      tattoos. The proximal rectum was then closed with sutures. The model was
      suspended in a trainer box by clamping the distal end in a ringed clamp and the
      proximal end to the box. Transanal excisions using TAMIS were then performed. The
      procedures were done by trained community colorectal surgeons attending courses
      on transanal minimally invasive surgery. RESULTS: Both partial- and full
      thickness excisions of sessile and pedunculated rectal lesions were successfully
      performed during simulated TAMIS by trained community surgeons learning this
      laparoendoscopic technique. CONCLUSION: Transanal laparoendoscopic procedures to
      excise rectal tumors can be successfully and reproducibly performed in an ex vivo
      porcine anorectal model.

PMID- 24680146
TI  - Port-site metastases after robotic surgery for gynecologic malignancy.
AB  - BACKGROUND AND OBJECTIVES: Robotic-assisted laparoscopic surgery is increasingly
      used for the management of patients with gynecologic malignancies. The rate of
      portsite metastases in patients undergoing these procedures is unknown. METHODS:
      We conducted a retrospective cohort analysis of a prospective database. A total
      of 220 women underwent robotic-assisted surgery from 2007 through 2011.
      Malignancy was detected in 145 cases, and 142 met the inclusion criteria with
      histologically proven cancer and robotically completed surgery. All women who
      underwent surgical treatment for their malignancies were followed up at the study
      site for oncology treatments. RESULTS: There were 710 potential port sites for
      metastasis. We found that 2 of 142 patients each had a single port-site
      metastasis, for an overall rate of 1.41%, or 0.28% per trocar site. Recurrent
      disease was not isolated in the two patients found to have port-site metastases
      because both had concurrent sites of pelvic recurrence. CONCLUSION: The rate of
      port-site metastases in patients undergoing robotic-assisted laparoscopic surgery
      for gynecologic malignancies is similar to the published rate in the literature
      for traditional laparoscopic oncology.

PMID- 24680147
TI  - Surgical management of adnexal masses in pregnancy.
AB  - BACKGROUND AND OBJECTIVES: Our objective was to review the surgical management,
      surgical outcomes, and obstetric outcomes of adnexal masses in pregnancy.
      METHODS: A retrospective review was performed of pregnant women before 20 weeks
      of gestation who underwent laparoscopy or laparotomy for management of an adnexal
      mass during the period of January 2005 to June 2012 at a university-affiliated
      hospital. RESULTS: Thirty-five pregnant women underwent surgical removal of
      adnexal masses during the 7.5-year study period: 21 (60.0%) underwent
      laparoscopic surgery, and 14 (40.0%) underwent laparotomy. The left upper
      quadrant entry technique was used in 20 women. Conversion to laparotomy was
      required in 2 women because of extensive pelvic adhesions. The mean gestational
      age at surgery was 15.2 +/- 1.9 weeks. All women had undergone ovarian
      cystectomy. A malignant mass was found in 3 (8.6%) women. The laparoscopy group
      had a significantly less blood loss (67.4 +/- 55.8 vs 153.6 +/- 181.0 mL, P =
      .048) and shorter mean hospital stay (2.8 +/- 1.0 vs 3.8 +/- 1.1 days, P = .006)
      than the laparotomy group. One woman miscarried soon after surgery. There was no
      significant difference in obstetric outcomes between the laparoscopy and
      laparotomy groups. CONCLUSION: Surgical management of adnexal masses during
      pregnancy appears to have favorable outcomes for the mother and the fetus.

PMID- 24680148
TI  - Transvaginal endoscopic surgery for tubal ectopic pregnancy.
AB  - OBJECTIVE: To explore the feasibility, safety, efficacy, and cosmetic outcomes of
      transvaginal endoscopic salpingectomy for tubal ectopic pregnancy. METHODS: From
      May 2009 to May 2012, we prospectively enrolled 40 patients, each of whom had
      been scheduled for a salpingectomy because of a tubal ectopic pregnancy, and
      randomized them into two groups: transvaginal endoscopic surgery and laparoscopic
      approach. We recorded the estimated blood loss, time of anal exhaust,
      postoperative pain score, length of stay, and scar assessment scale associated
      with transvaginal endoscopic access (n = 18) (natural orifice transluminal
      endoscopic surgery) and laparoscopic salpingectomy (n = 20) (control group) for
      tubal ectopic pregnancy. The transvaginal salpingectomy was performed with a
      double-channel endoscope through a vaginal puncture. A single surgeon performed
      the surgical procedures in patients in both groups. RESULTS: The group that
      underwent the transvaginal endoscopic procedure reported lesser pain at all
      postoperative visits than the group that underwent the laparoscopic approach. The
      duration of time for transvaginal endoscopic surgery was slightly longer than
      that for the laparoscopic approach. However, there was no statistically
      significant difference between the two groups in the duration of operative time.
      The group that underwent transvaginal endoscopic surgery was more satisfied with
      the absence of an external scar than the group that underwent the laparoscopic
      procedure, which left a scar. The estimated blood loss, time of anal exhaust, and
      length of stay were the same in both groups. CONCLUSION: The safety and efficacy
      of transvaginal endoscopic salpingectomy for tubal ectopic pregnancy are
      equivalent to those of the laparoscopic procedure. Lesser postoperative pain and
      a more satisfactory cosmetic outcome were found with the transvaginal endoscopic
      procedure, making it the more preferred method and superior to the laparoscopic
      approach.

PMID- 24680149
TI  - Barbed suture for vaginal cuff closure in laparoscopic hysterectomy.
AB  - BACKGROUND AND OBJECTIVES: Our aim was to evaluate whether the use of barbed
      suture for vaginal cuff closure is associated with a decrease in postoperative
      vaginal bleeding compared with cuff closure with polyglactin 910 in patients who
      have undergone laparoscopic hysterectomy. METHODS: We performed a cohort study of
      patients who underwent laparoscopic hysterectomy between January 2008 and July
      2012 by the minimally invasive gynecologic surgery division of the Gynecology,
      Obstetrics and Human Reproduction Department at Fundacion Santa Fe de Bogota
      University Hospital, Bogota, Colombia. RESULTS: A total of 232 women were
      studied: 163 were in the polyglactin 910 group, and 69 were in the barbed suture
      group. The main outcome, postoperative vaginal bleeding, was documented in 53
      cases (32.5%) in the polyglactin 910 group and in 13 cases (18.8%) in the barbed
      suture group (relative risk, 0.57; 95% confidence interval, 0.34-0.9; P = .03).
      No statistically significant differences were found in other postoperative
      outcomes, such as emergency department admission, vaginal cuff dehiscence,
      infectious complications, and the presence of granulation tissue. CONCLUSION: In
      this study an inverse association was observed between the use of barbed suture
      for vaginal cuff closure during laparoscopic hysterectomy and the presence of
      postoperative vaginal bleeding.

PMID- 24680150
TI  - Laparoscopic hysterectomy and prolapse: a multiprocedural concept.
AB  - BACKGROUND AND OBJECTIVES: Today, laparoscopic intrafascial hysterectomy and
      laparoscopic supracervical hysterectomy are well-accepted techniques. With our
      multimodal concept of laparoscopic hysterectomy for benign indications,
      preservation of the pelvic floor as well as reconstruction of pelvic floor
      structures and pre-existing prolapse situations can be achieved. METHODS: The
      multimodal concept consists of 3 steps: 1. Intrafascial hysterectomy with
      preservation of existing structures. A. Technique 1: Primary uterine artery
      ligation. B. Technique 2: Classic intrafascial hysterectomy. 2. A technique for
      the stable fixation of the vaginal or cervical stump. 3. A new method of
      pectopexy to correct a pre-existing descensus situation. RESULTS AND CONCLUSTION:
      This well-balanced concept can be used by advanced endoscopic gynecologic
      surgeons as well as by novices in our field.

PMID- 24680151
TI  - Gene expression profiling of human kidneys undergoing laparoscopic donor
      nephrectomy.
AB  - BACKGROUND AND OBJECTIVES: The objective was to compare gene expression profiles
      of 6 kidneys from open donor nephrectomy with 6 kidneys removed after
      laparoscopic donor nephrectomy and several hours of carbon dioxide
      pneumoperitoneum with DNA microarrays and identify small-molecule drugs. METHODS:
      The gene expression profile GSE3297 was downloaded from the Gene Expression
      Omnibus database, and the differentially expressed genes were identified by a
      bioinformatics approach. First, Osprey software was used to construct a
      differentially expressed gene associated network. Then, DAVID (Database for
      Annotation, Visualization, and Integrated Discovery) and FuncAssociate were used
      to perform functional analyses. Finally, the Connectivity Map was used to screen
      for small-molecule drugs. RESULTS: A total of 285 differentially expressed genes
      were identified, including 148 down-regulated genes and 137 up-regulated genes.
      In addition, the differentially expressed genes in the most significant Gene
      Ontology term were CASP6, KRAS, SOCS1, ESR1, TSHB, COL1A1, and MMP14.
      Furthermore, several differentially expressed genes, including STAT1, STAT6,
      SOS2, and SOCS1, participated in the most remarkable Janus kinase-signal
      transducer and activator of transcription signaling pathway. Finally, luteolin-
      with the highest score (0.887)--was identified as the small-molecule drug.
      CONCLUSIONS: Our data show an altered renal transcriptome induced by several
      hours of carbon dioxide pneumoperitoneum and laparoscopic surgery characterized
      by up-regulation of genes associated with acute inflammation, apoptosis, and
      immune injury, which could potentially result in renal injury and an enhanced
      immune response in the recipient after transplant.

PMID- 24680152
TI  - Robotic laparoscopic pyeloplasty.
AB  - BACKGROUND AND OBJECTIVES: We aimed to assess the feasibility and outcomes of
      complex ureteropelvic junction obstruction cases submitted to robotic-assisted
      laparoscopic pyeloplasty. METHODS: The records of 131 consecutive patients who
      underwent robotic-assisted laparoscopic pyeloplasty were reviewed. Of this
      initial population of cases, 17 were considered complex, consisting of either
      atypical anatomy (horseshoe kidneys in 3 patients) or previous ureteropelvic
      junction obstruction management (14 patients). The patients were divided into 2
      groups: primary pyeloplasty (group 1) and complex cases (group 2). RESULTS: The
      mean operative time was 117.3 +/- 33.5 minutes in group 1 and 153.5 +/- 31.1
      minutes in group 2 (P = .002). The median hospital stay was 5.19 +/- 1.66 days in
      group 1 and 5.90 +/- 2.33 days in group 2 (P = .326). The surgical findings
      included 53 crossing vessels in group 1 and 5 in group 2. One patient in group 1
      required conversion to open surgery because of technical difficulties. One
      patient in group 2, with a history of hemorrhagic rectocolitis, presented with
      peritonitis postoperatively due to a small colonic injury. A secondary procedure
      was performed after the patient had an uneventful recovery. At 3 months,
      significant improvement (clinical and radiologic) was present in 93% of cases in
      group 1 and 88.2% in group 2. At 1 year, all patients in group 2 showed
      satisfactory results. At a late follow-up visit, 1 patient in group 1 presented
      with a recurrent obstruction. CONCLUSIONS: Robotic pyeloplasty appear to be
      feasible and effective, showing a consistent success rate even in complex
      situations. Particular care should be observed during the colon dissection in
      patients with previous colonic pathology.

PMID- 24680153
TI  - Laparoscopic nephropexy with polymer clips.
AB  - BACKGROUND AND OBJECTIVES: We present our initial experience and long-term
      results with transperitoneal laparoscopic nephropexy with nonabsorbable polymer
      clips. METHODS: Seven patients aged 34 to 47 years previously diagnosed with
      mobile kidney presented with chronic pain refractory to analgesics and underwent
      a transperitoneal laparoscopic nephropexy procedure with nonabsorbable polymer
      clips by fixing the perirenal tissue to the transversus abdominis fascia and
      triangular ligament. RESULTS: Mean operation time was 20 minutes. All patients
      were discharged after 24 hours. Follow-up intravenous pyelogram (IVP) at 60 and
      150 days showed the right kidneys in a more cephalad position, and showed
      pelvicaliceal dilatations and that the ureteral kinks seemed to be resolved. On
      days 15, 60, 90, and 150 of the first- and second-year follow-ups, severity of
      pain was 1 of 10 on the visual analog scale. CONCLUSION: We believe that the
      technique of transperitoneal laparascopic nephropexy with nonabsorbable polymer
      clips on patients with symptomatic mobile kidney is safe and easy to perform and
      shows successful long-term results.

PMID- 24680154
TI  - Laparoscopic resection of symptomatic gastric diverticula.
AB  - Gastric diverticula are rare and usually asymptomatic. This report, however,
      describes two examples of symptomatic gastric diverticula successfully treated by
      laparoscopic resection. Both patients were male and in their sixth decade of
      life. One patient was relatively healthy with no past medical history, whereas
      the other patient had chronic pain issues and at presentation was also undergoing
      evaluation for hyperaldosteronism. The patients presented with gastrointestinal
      symptoms, including nausea, emesis, abdominal pain, and change in bowel function.
      In both cases, a gastric diverticulum was identified by CT scan, and precise
      anatomic position was determined by upper endoscopy. After discussion with the
      treating teams, including a gastroenterologist and surgeon, surgical treatment
      and resection was elected. Successful laparoscopic removal was accomplished in
      both patients, and they were discharged home after tolerating liquid diets. Both
      patients reported resolution of their abdominal symptoms at follow-up. 

PMID- 24680155
TI  - Portal vein thrombosis after laparoscopic cholecystectomy.
AB  - INTRODUCTION: Portal vein thrombosis (PVT) is a relatively uncommon complication
      after abdominal surgery. CASE REPORT: We report an even more unusual case of PVT
      10 days after an uncomplicated laparoscopic cholecystectomy, believed to be only
      the fourth reported case in the literature of this rare complication. CONCLUSION:
      Albeit extremely rare, PVT should be included in the differential diagnosis for
      abdominal symptoms and/or elevated hepatic function tests after laparoscopic
      cholecystectomy.

PMID- 24680156
TI  - Total laparoscopic modified Duhamel operation in combination with transanal
      endoscopic microsurgery.
AB  - INTRODUCTION: Laparoscopic-assisted colonic resection has been well described for
      multiple surgical indications and typically requires an abdominal incision for
      specimen removal that is associated with most of the postoperative pain. We
      report the total laparoscopic modified Duhamel operation for megacolon in
      combination with transanal endoscopic microsurgery for transanal specimen
      retrieval and anastomosis to avoid the additional abdominal extraction incision.
      CASE DESCRIPTION: Two cases are presented: case 1 was a 15-year-old boy who
      presented with intermittent abdominal distention, pain, and constipation for 3
      years' duration and was diagnosed with Hirschsprung disease, and case 2 was a 60
      year-old man who presented with repeated attacks of incomplete intestinal
      obstruction for 2 years' duration and was diagnosed with adult megacolon. They
      were treated by the total laparoscopic modified Duhamel operation without an
      abdominal extraction incision in combination with transanal endoscopic
      microsurgery. The operations were successfully accomplished without conversion to
      open surgery. The patients tolerated the procedure well, complained of minimal
      postoperative pain, and did not require narcotics beyond the day of the
      operation. No surgical complications occurred. Discharge from the hospital
      occurred on the ninth postoperative day in case 1 and the 13th postoperative day
      in case 2. DISCUSSION: The total laparoscopic modified Duhamel operation in
      combination with transanal endoscopic microsurgery is a feasible and minimally
      invasive technique for idiopathic megacolon and adult megacolon. This advanced
      surgical technique was developed by combining laparoscopy with the concept of
      natural orifice transluminal endoscopic surgery.

PMID- 24680157
TI  - Single-incision laparoscopic Ladd's procedure for intestinal malrotation.
AB  - INTRODUCTION: The potential of single-incision laparoscopic surgery (SILS) as a
      less invasive and more cosmetically appealing technique has prompted the
      expansion of its adoption. SILS has been shown to be a safe and feasible
      alternative to traditional multiport cholecystectomy, appendectomy, colectomy,
      and many other laparoscopic procedures. The objective of this study is to provide
      an initial report of the feasibility of correcting intestinal malrotation via a
      single-incision laparoscopic transumbilical approach. CASE DESCRIPTION: A 29-year
      old woman presented with symptomatic congenital intestinal malrotation. She
      elected to undergo a Ladd's procedure using a single-incision laparoscopic
      approach with a SILS port and standard laparoscopic instruments. The procedure
      was accomplished without additional ports or conversion to laparotomy, and no
      intraoperative or postoperative complications were noted. Total operative time
      was 106 minutes. The patient had minimal postoperative pain and was satisfied
      with the cosmetic outcome. CONCLUSION: When performed by a surgeon experienced in
      the SILS technique, single-incision laparoscopic Ladd's procedure for symptomatic
      intestinal malrotation in an adult is feasible and safe, with minimal
      postoperative pain and favorable cosmetic outcome.

PMID- 24680158
TI  - Intraperitoneal and extraperitoneal colonic perforation following diagnostic
      colonoscopy.
AB  - Both intraperitoneal and extraperitoneal colonic perforations have been reported
      after colonoscopy; however, cases with combined types of perforation are rare. We
      present the case of a 55-year-old man with a history of Crohn disease who
      complained of acute abdominal pain after a diagnostic colonoscopy. Abdominal
      computed tomography scan showed extensive pneumoperitoneum,
      pneumoretroperitoneum, pneumomediastinum, and leftsided pneumothorax. Exploratory
      laparotomy was performed, and the patient underwent subtotal colectomy and end
      ileostomy with placement of a left-sided chest drain for the left-sided
      pneumothorax. The patient was discharged home postoperatively in good condition.
      As the utility of colonoscopy continues to broaden, its complications will also
      be more common. Whereas intraperitoneal perforation is a known and not uncommon
      complication, extraperitoneal perforation is an uncommon complication. Combined
      intraperitoneal and extraperitoneal perforation is extremely rare, with only a
      few cases reported in the literature. Early diagnosis and operative management
      resulted in a satisfactory outcome in this particular case. 

PMID- 24680159
TI  - Perforated small bowel diverticulitis after gastric bypass.
AB  - We report a rare case of complicated jejunal diverticulitis in a patient with
      previous bariatric surgery. Small bowel diverticulosis is generally considered an
      inoffensive disease. In this report we describe a case of small bowel perforation
      in an obese subject who had undergone laparoscopic Roux-en-Y gastric bypass. 

PMID- 24680160
TI  - Robot-assisted resection of a retrocaval peridiaphragmatic mass.
AB  - A peridiaphragmatic mass that is located in the retrocaval space typically
      requires a wide incision and retraction of the peritoneal organs or great vessels
      to remove the mass. The laparoscopic method is very challenging because of
      unsatisfactory visual fields and a lack of range of movement from the
      instruments. We present the advantages of robotic surgery in the removal of deep
      retrocaval tumors, a procedure that requires careful dissection and minimal
      retraction. 

PMID- 24680161
TI  - Robot-assisted excision of a large retroperitoneal schwannoma.
AB  - INTRODUCTION: There are few case reports of retroperitoneal tumor excision using
      the robotic technique. We describe a case of a 13 * 9 * 7- cm retroperitoneal
      schwannoma that was excised using robot-assisted surgery to provide a minimally
      invasive benefit to the patient. CASE REPORT: A 45-year-old woman presented with
      a right paracaval retroperitoneal lump with well-defined margins displacing the
      inferior vena cava, the right kidney, the head of pancreas, and the duodenum. She
      underwent a robot-assisted excision of the tumor using the da Vinci Si HD
      surgical system using three robotic arms. The biopsy results revealed a well
      encapsulated schwannoma diffusely positive for S100. The patient was discharged
      on the third postoperative day and was still doing well at 1-month follow-up.
      CONCLUSION: Use of robotic technology assists in providing minimally invasive
      benefits to the patient. It is a safe and effective technique for retroperitoneal
      surgery.

PMID- 24680162
TI  - Laparoscopic splenectomy for isolated splenic sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis is an inflammatory disease with an unknown etiology.
      The pulmonary interstitium is mainly involved, with noncaseating granulomas and
      lymphadenopathy. It is a multisystemic disease, and the differential diagnosis
      should include infectious, neoplastic, and autoimmune diseases to prevent
      inappropriate treatment and unnecessary surgery. Abdominal disease without
      evidence of pulmonary abnormalities on chest radiography in sarcoidosis can be
      found in approximately 25% to 38% of cases. The approach to isolated splenic
      nodules in a patient with nonspecific abdominal symptoms should be focused on
      exclusion of malignancies and infections, and may require computed tomography,
      magnetic resonance imaging, and positron emission tomography- computed tomography
      imaging; scintigraphy; bone marrow biopsy; breast and genital examinations; and
      endoscopies. This report documents a rare case of isolated granulomatous disease
      of the spleen that was diagnosed and treated laparoscopically. CASE: A 29-year
      old woman presented with nonspecific complaints such as nausea, vomiting, and
      epigastric discomfort. Further laboratory test results were normal. Abdominal
      ultrasonography, computed tomography, and magnetic resonance imaging revealed
      multiple splenic lesions. Additional examination findings were negative for
      occult neoplasia or infectious disease. Laparoscopic splenectomy was performed as
      a diagnostic procedure, without complications, and the final diagnosis was
      sarcoidosis. CONCLUSION: Isolated splenic sarcoidosis is a rare manifestation of
      extrapulmonary disease. The final diagnosis may be achieved only by histology,
      requiring biopsy or splenectomy. Minimally invasive surgery is a safe and
      efficient method for diseases of the spleen and should be the first option when
      feasible. The patient did well; however, further monitoring is required to
      diagnose recurrence.

PMID- 24680163
TI  - Hand-assisted laparoscopic surgery for a mesenteric teratoma.
AB  - Mature cystic teratomas are benign neoplasms of germ cell tumors that occur most
      frequently in gonadal sites. The tumors usually contain 2 or 3 well
      differentiated elements of endodermal, ectodermal, and mesodermal origin.
      Although relatively uncommon, teratomas can be composed of mature tissue
      originating from only 1 germ cell layer. This is known as a monodermal teratoma.
      Extragonadal teratomas, especially mesenteric teratomas, are extremely rare.
      Currently, only 21 cases of mesenteric teratoma have been described in the
      English literature. Mesenteric teratomas are rarely diagnosed preoperatively
      because pathological examination is necessary to make a definitive diagnosis. We
      herein report a rare case of mesenteric monodermal teratoma and review the
      literature. To the best of our knowledge, this is the first case of mesenteric
      teratoma treated with hand-assisted laparoscopic surgery. 

PMID- 24680164
TI  - Lethal cervical abscess following bisphosphonate related osteonecrosis of the
      jaw.
AB  - CONTEXT: Bisphosphonates are common drugs used in the management of bone
      metabolic diseases. Because of their recently increased use, their adverse
      effects, especially bisphosphonate-related osteonecrosis of the jaw (BRONJ), are
      monitored more frequently. BRONJ is a critical challenge in craniofacial surgery
      and is difficult to treat. Its occurrence is either spontaneous or follows
      dentoalveolar surgery. Typical complications of BRONJ are painful exposed bone,
      pathological fractures, extra-oral fistula, and local infections. OBJECTIVE: The
      aim of this paper is to report a rare case of bacterial embolism in the internal
      jugular vein after a BRONJ-induced submandibular abscess resulting in bacterial
      sepsis, multi-organ failure syndrome, and death. CASE ILLUSTRATION: A 59-year-old
      female patient developed severe BRONJ (stage II) with recurrent abscesses after
      oral osteoporosis therapy with alendronic acid. A subsequent submandibular
      abscess led to bacterial embolism of the left internal jugular vein, causing
      sepsis and death. DISCUSSION: Prevention, early detection and management of BRONJ
      remain a crucial challenge in craniofacial clinical practice. Despite several
      therapeutic approaches described in the current literature, none have undergone
      bedside application. CONCLUSION: Considering this report of death after recurrent
      abscesses following BRONJ, the use of bisphosphonates should be carefully
      monitored in order to prevent such severe complications.

PMID- 24680165
TI  - Mapping the relationships between work and sustainability and the opportunities
      for ergonomic action.
AB  - A map was drawn up of the relationships between work (in its multiple
      interpretations) and sustainability (sustainable development and corporate
      sustainability) based on a bibliographic analysis of articles that discuss these
      themes jointly in the current academic literature. The position of the discipline
      of ergonomics focused on work was identified from this map and, based on its
      specific academic literature, it was possible to identify where this discipline
      could contribute so that work and workers can be included in the discourse of
      sustainable development and considered in corporate sustainability policies.
      Ergonomics can be actively influential within the organization on issues relating
      to work improvements; it may boost integrated increases in the organization's
      performance and in workers' well-being; it can provide support for changes and
      new (environmental) sustainability-related work requirements to be considered;
      and it can contribute to the definition of the concept of work in a context of
      sustainable development. 

PMID- 24680166
TI  - Fabricating a fiber-reinforced post and zirconia core with CAD/CAM technology.
AB  - This article describes a technique for overcoming the limitations of dental
      scanners in imaging post spaces by using a single fiber-reinforced post and
      computer-aided design and computer-aided manufacturing (CAD/CAM) technology,
      thereby eliminating the need for a 'Scan Post' and the post and core module in
      the CAD. This technique produces an anatomically correct core and ensures the
      correct thickness of crown restorations. 

PMID- 24680167
TI  - Direct composite resin layering techniques for creating lifelike CAD/CAM
      fabricated composite resin veneers and crowns.
AB  - Direct composite resin layering techniques preserve sound tooth structure and
      improve function and esthetics. However, intraoral placement techniques present
      challenges involving isolation, contamination, individual patient
      characteristics, and the predictability of restorative outcomes. Computer-aided
      design and computer-aided manufacturing (CAD/CAM) restorations enable dentists to
      better handle these variables and provide durable restorations in an efficient
      and timely manner; however, milled restorations may appear monochromatic and lack
      proper esthetic characteristics. For these reasons, an uncomplicated composite
      resin layering restoration technique can be used to combine the benefits of
      minimally invasive direct restorations and the ease and precision of indirect
      CAD/CAM restorations. Because most dentists are familiar with and skilled at
      composite resin layering, the use of such a technique can provide predictable and
      highly esthetic results. This article describes the layered composite resin
      restoration technique.

PMID- 24680168
TI  - Cycloartane triterpenes from the leaves of Neoboutonia macrocalyx L.
AB  - Neoboutonia macrocalyx is used by people in south western Uganda around Kibale
      National Park in the treatment of malaria. Phytochemical investigation on the
      leaves of this plant led to the isolation of nine cycloartane triterpenes (1-9)
      and one phenanthrene; 7-methoxy-2,8 dimethyl-9,10-dihydrophenantherene-3,6 diol
      (10) along with three known compounds which included 22-de-O-acetyl-26
      deoxyneoboutomellerone (11), mellerin B (12) and 6-hydroxystigmast-4-en-3-one
      (13). The chemical structures of the compounds were established mainly through a
      combination of spectroscopic techniques. The isolated compounds were evaluated
      for antiplasmodial activity against the chloroquine-resistant FcB1/Colombia
      strain of Plasmodium falciparum and for cytotoxicity against the KB
      (nasopharyngeal epidermoid carcinoma) and MRC-5 (human diploid embryonic lung)
      cells. Seven out of 13 compounds exhibited good antiplasmodial activity with IC50
      of ?5MUg/ml with two compounds exhibiting low cytotoxicity and five compounds
      having significant cytotoxicity. 

PMID- 24680169
TI  - Recent advances in antidotes for direct oral anticoagulants: their arrival is
      imminent.
AB  - The results of early trials evaluating the tolerability, efficacy,and safety of
      specific antidotes for the DOACs are promising (Table 2), but none of these
      agents are as yet approved for clinical use. Until they are approved, clinicians
      attempting to reverse the anticoagulant effects of DOACs will be limited to the
      use of general hemostatic agents, such as(activated) PCCs or rFVIIa,3-12 and to
      hemodialysis or hemofiltration for removal of DOACs that are not highly protein
      bound.The overall goal of using reversal agents is to prevent morbidity and
      mortality.23 Even without specific antidotes, the randomized trials have
      demonstrated that DOACs compared with standard therapies are associated with
      similar or lower rates of major bleeding and lower rates of intracranial
      bleeding,2,24 with similar or lower mortality rates after bleeding.25,26 In order
      to be approved for clinical use, future trials with specific antidotes will need
      to demonstrate their efficacy in clinical studies involving patients treated with
      DOACs. At this stage however, it is unclear whether regulatory agencies will
      require evidence of control of bleeding or whether demonstration of reversal of
      anticoagulant effects of DOACs will be sufficient for their approval.
      Demonstration of hemostatic efficacy will be challenging because bleeding of
      sufficient severity to require reversal of DOACs is uncommon, the half-life of
      DOACs are short, creating a limited window to administer the antidote, and the
      appropriate outcome measure for such studies is uncertain.However, because the
      overall goal of reversal agents is to prevent morbidity and mortality rather than
      to normalize prolonged coagulation tests, demonstration of hemostatic efficacy
      will be essential to establish that specific antidotes for DOACs can also make a
      clinically important difference.

PMID- 24680170
TI  - Next-generation airbags and the possibility of negative outcomes due to thoracic
      injury.
AB  - Airbags have been shown to decrease morbidity and mortality associated with motor
      vehicle accidents when used in conjunction with seat belts. Airbag deployment
      alone however, has recently been implicated as a cause of significant thoracic
      injuries to unrestrained drivers. Resulting injuries include major cardiovascular
      and pulmonary complications. Airbags provide safety to occupants of cars and
      reduce mortality by 25%-30%. When not used in accordance with international
      standards, however, they can cause serious injury. We searched online databases
      from 1970 to January 2013 and included 17 retrospective studies, 12 systematic
      review articles, 18 case reports, 5 prospective studies, 1 lab study, 3 cohort
      studies, and 1 meta-analysis. Outcomes included clinical/functional response,
      left ventricular remodelling, hospitalizations, and mortality. Physicians must
      maintain a high index of suspicion for injury when evaluating drivers who were
      not wearing seat belts when airbags deployed, regardless of the speed of the
      collision, because increased risk of thoracic injury with airbags has been
      described in the literature. Our review indicates that even new technology,
      specifically the side air bag, has been associated with a risk of thoracic
      injury. Considering that regulations are a driving force for airbag technology,
      further research and scrutiny by medical teams is needed to consider the effects
      of airbag technology advancements on morbidity and mortality rates of car
      accidents, to help in guiding further improvement, and to help lawmakers in
      implementing rules that protect the safety of occupants. 

PMID- 24680171
TI  - Optical coherence tomography-guided primary percutaneous coronary intervention in
      ST-segment elevation myocardial infarction patients: a pilot study.
AB  - BACKGROUND: The objective of our study was to assess whether optical coherence
      tomography (OCT) guidance could guide intervention to avoid balloon angioplasty
      and stenting during primary percutaneous coronary intervention. METHODS: One
      hundred patients with ST-segment elevation myocardial infarction and thrombus
      containing lesion were enrolled in this study. Thrombus aspiration was performed
      in all cases followed by an OCT study. After thrombectomy, no stent was implanted
      in residual significant stenosis (> 50%) if examination using OCT suggested that
      the occlusion was mostly thrombotic, provided that the patient was symptom-free
      and the Thrombolysis in Myocardial Infarction (TIMI) flow was >= 2. All patients
      managed only using thrombectomy underwent 1-week and 9-month angiography and OCT.
      Patients with significant lesion or those in whom thrombectomy failed to re
      establish flow underwent standard treatment. RESULTS: Based on the OCT
      information, 20 patients (20%) were treated only with aspiration even in the
      presence of angiographically detected "high-grade stenosis." Angiogram and OCT
      performed at 1 week and 9 months showed a "normal vessel" without significant
      stenosis in all 20 cases. There were no cases of major adverse cardiovascular
      event (including death, myocardial infarction, and target lesion
      revascularization) during the in-hospital period or at the 12-month follow-up.
      CONCLUSIONS: The results of our pilot study suggest that ST segment elevation
      myocardial infarction patients with TIMI 2/3 flow in the angiogram and without
      significant coronary narrowing using OCT examination (even in the presence of
      angiographically detected "high-grade stenosis"), in whom thrombus aspiration is
      performed in addition to optimal medical therapy might benefit only from thrombus
      aspiration without plain old balloon angioplasty/stenting during primary
      percutaneous coronary intervention. Validation of these preliminary data in
      larger randomized studies is warranted.

PMID- 24680172
TI  - Lower blood vitamin D levels are associated with an increased incidence of
      contrast-induced nephropathy in patients undergoing coronary angiography.
AB  - BACKGROUND: Vitamin D deficiency may be associated with an increased risk of
      renovascular disease. We assessed the correlation between vitamin D levels and
      contrast-induced nephropathy (CIN) in patients undergoing coronary angiography
      (CAG). METHODS: Vitamin D and parathyroid hormone (PTH) levels were assessed
      before CAG in 403 patients. Estimated glomerular filtration rate (eGFR) was
      calculated using the Cockcroft-Gault equation. Patients with eGFR < 60
      mL/min/1.73 m(2) were hydrated with 0.9%-saline at 1 mL/kg/h for 12 hours before
      and after CAG. CIN was defined as serum creatinine increase of > 0.5 mg/dL or >
      25% within 48-72 hours after CAG. RESULTS: CIN developed in 74 participants.
      Baseline eGFR, blood urea and creatinine in CIN (+) and (-) groups were not
      significantly different (P = 0.14, P = 0.07, and P = 0.61, respectively). Total
      volume of contrast medium (CM) was higher in the CIN (+) group (132 +/- 64 mL vs
      90 +/- 41 mL; P = 0.01). Vitamin D levels were lower (median 8.5 [range, 0.5
      26.6] ng/mL vs 14.9 [range, 1.9-93.5] ng/mL; P = 0.01) and PTH levels were higher
      (median 73.9 [range, 22-530] pg/mL vs 44.2 [range, 5-361] pg/mL; P = 0.01) in the
      CIN (+) group. Multivariate logistic regression analysis revealed that lower
      vitamin D levels (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.11-1.26;
      P = 0.01) and increased CM volume (OR, 1.01; 95% CI, 1.008-1.017; P = 0.01) were
      independently correlated with CIN. In patients who had undergone percutaneous
      coronary intervention, lower levels of vitamin D were independently associated
      with CIN development. CONCLUSIONS: Lower vitamin D levels, implying possible
      vitamin D deficiency, are associated with a higher incidence of CIN.

PMID- 24680174
TI  - A systematic review of the diagnostic accuracy of cardiovascular magnetic
      resonance for pulmonary hypertension.
AB  - BACKGROUND: The diagnostic accuracy of cardiovascular magnetic resonance (CMR)
      for pulmonary hypertension (PH) compared with right heart catheterization were
      assessed. The purpose of this systematic review was to comprehensively evaluate
      the diagnostic accuracy of CMR in evaluating PH. METHODS: Published literature
      was obtained from PUBMED, Web of Knowledge, Cochrane library, Embase, Biosis
      Preview, China National Knowledge Infrastructure, and Chongqing VIP databases,
      and all studies were inclusive until December 2012. Studies relevant to PH and
      its imaging in CMR and right heart catheterization were included if correlation
      coefficient was elucidated clearly. Quality Assessment of Diagnostic Accuracy
      Studies 2 (QUADAS-2) score was used to assess the quality of studies. Sensitivity
      and specificity were pooled separately and compared with overall accuracy
      measures: diagnostic odds ratio and symmetric summary receiver operating
      characteristic. RESULTS: Sixteen studies were included in the systematic review.
      Of all the studies, the most widely used index was ventricular mass index (VMI)
      of CMR. We performed a meta-analysis for VMI among 429 patients in 5 individual
      studies, which showed a modest diagnostic accuracy of VMI for PH with a summary
      sensitivity and specificity of 84% (95% confidence interval, 79%-87%) and 82%
      (95% confidence interval, 73%-89%), respectively. In addition, the summary
      positive likelihood ratio was 4.894, indicating that VMI of CMR allows a modest
      ability to distinguish PH patients from healthy subjects with a cutoff point of
      0.45 using functional and structural measures. CONCLUSIONS: This systematic
      review and meta-analysis indicates that VMI seems to have a moderate sensitivity
      and specificity for detection of PH. The application values of other parameters
      still need further investigation.

PMID- 24680173
TI  - Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND: The association between habitual caffeine intake with incident atrial
      fibrillation (AF) was unknown. We conducted a meta-analysis to investigate the
      association between chronic exposure of caffeine and the risk of AF and to
      evaluate the potential dose-response relation. METHODS: We searched PubMed,
      EMBASE, and the Cochrane Library up to November 2013 and references of relevant
      retrieved articles. Prospective cohort studies were included with relative risk
      (RR) or hazard ratio and 95% confidence intervals (CIs) for AF according to
      coffee/caffeine intake. RESULTS: Six prospective cohort studies with 228,465
      participants were included. In the primary meta-analysis, caffeine exposure was
      weakly associated with a reduced risk of AF (RR, 0.90; 95% CI, 0.81-1.01; P =
      0.07; I(2) = 73%). In subgroup analyses, pooled results from studies with
      adjustment of potential confounders showed an 11% reduction for low doses (RR,
      0.89; 95% CI, 0.80-0.99, P = 0.032; I(2) = 30.9%, P = 0.227) and 16% for high
      doses (RR, 0.84; 95% CI, 0.75-0.94, P = 0.002; I(2) = 24.1%, P = 0.267) of
      caffeine consumption in AF risk. An inverse relation was found between habitual
      caffeine intake and AF risk (P for overall trend = 0.015; P for nonlinearity =
      0.27) in dose-response meta-analysis and the incidence of AF decreased by 6% (RR,
      0.94; 95% CI, 0.90-0.99) for every 300 mg/d increment in habitual caffeine
      intake. CONCLUSIONS: It is unlikely that caffeine consumption causes or
      contributes to AF. Habitual caffeine consumption might reduce AF risk.

PMID- 24680175
TI  - Pure right ventricular infarction resulting from coronary ectasia: importance of
      diagnostic imaging.
AB  - Isolated right ventricular (RV) infarction may occur during percutaneous coronary
      intervention resulting from selective occlusion of a ventricular branch of the
      right coronary artery (RCA). We present a case of a pure RV infarction without
      iatrogenic origin that at the initial electrocardiographic analysis was
      suggestive of a left anterior descending artery-related acute myocardial
      infarction. Coronary angiography results made us suspect thrombotic occlusion of
      a small branch of the ectatic RCA resulting from slow flow. Final diagnosis was
      confirmed by coronary computed tomographic angiography and cardiac magnetic
      resonance imaging, underlining the essential diagnostic role of these imaging
      modalities. 

PMID- 24680177
TI  - Diagnosing bone lesions: a practical non-pathology centric formulaic approach.
AB  - Bone lesions are perceived to be some of the most difficult lesions that
      pathologists encounter. The reasons for this are multiple and include lack of
      experience/familiarity, the need to rely heavily on non-pathology information and
      data, and the fact that many lesions are associated with either procedures or
      treatments with significant morbidity. However, in fact, the majority of bone
      lesions can be accurately assessed on the basis of data not directly related to
      traditional pathologic based assessment. In order to achieve this state, the
      pathologist must understand the consistent clinical parameters of most bone
      lesions, including their clinical presentation, the bone involved, particularly
      the anatomic site of the bone involved, and a fundamental, basic understanding of
      imaging studies, especially the plain radiograph. Once these principles are
      understood and mastered, the pathologist can easily diagnose most bone lesions,
      using traditional pathologic assessment to confirm the diagnosis.

PMID- 24680176
TI  - Tumor suppression effects of bilberry extracts and enzymatically modified
      isoquercitrin in early preneoplastic liver cell lesions induced by piperonyl
      butoxide promotion in a two-stage rat hepatocarcinogenesis model.
AB  - To investigate the protective effect of bilberry extracts (BBE) and enzymatically
      modified isoquercitrin (EMIQ) on the hepatocarcinogenic process involving
      oxidative stress responses, we used a two-stage hepatocarcinogenesis model in N
      diethylnitrosamine-initiated and piperonyl butoxide (PBO)-promoted rats. We
      examined the modifying effect of co-administration with BBE or EMIQ on the liver
      tissue environment including oxidative stress responses, cell proliferation and
      apoptosis, and phosphatase and tensin homolog (PTEN)/Akt and transforming growth
      factor (TGF)-beta/Smad signalings on the induction mechanism of preneoplastic
      lesions during early stages of hepatocellular tumor promotion. PBO increased the
      numbers and area of glutathione S-transferase placental form (GST-P)(+) liver
      cell foci and the numbers of Ki-67(+) proliferating cells within GST-P(+) foci.
      Co-administration of BBE or EMIQ suppressed these effects with the reductions of
      GST-P(+) foci (area) to 48.9-49.4% and Ki-67(+) cells to 55.5-61.4% of the PBO
      promoted cases. Neither BBE nor EMIQ decreased microsomal reactive oxygen species
      induced by PBO. However, only EMIQ suppressed the level of thiobarbituric acid
      reactive substances to 78.4% of the PBO-promoted cases. PBO increased the
      incidences of phospho-PTEN(-) foci, phospho-Akt substrate(+) foci, phospho-Smad3(
      ) foci and Smad4(-) foci in GST-P(+) foci. Both BBE and EMIQ decreased the
      incidences of phospho-PTEN(-) foci in GST-P(+) foci to 59.8-72.2% and Smad4(-)
      foci to 62.4-71.5% of the PBO-promoted cases, and BBE also suppressed the
      incidence of phospho-Akt substrate(+) foci in GST-P(+) foci to 75.2-75.7% of the
      PBO-promoted cases. These results suggest that PBO-induced tumor promotion
      involves facilitation of PTEN/Akt and disruptive TGF-beta/Smad signalings without
      relation to oxidative stress responses, but this promotion was suppressed by co
      treatment with BBE or EMIQ through suppression of cell proliferation activity of
      preneoplastic liver cells. 

PMID- 24680178
TI  - Cartilage-forming tumors.
AB  - Cartilage-forming tumors as a group are the most common primary bone tumors; this
      is largely due to the common occurrence of asymptomatic benign lesions such as
      osteochondroma and enchondroma. The common feature of these tumors is the
      presence of chondrocytic cells and the formation of cartilaginous tumor matrix.
      Some of these tumors are true neoplasms while others are hamartomas or
      developmental abnormalities. The morphologic heterogeneity of these tumors may be
      explained by a common multipotent mesenchymal cell differentiating along the
      lines of fetal-adult cartilage maturation. Recently mutations in IDH1 and IDH2
      have been detected in a variety of benign and malignant cartilaginous tumors.(1
      4.)

PMID- 24680179
TI  - Osteogenic tumors of bone.
AB  - In this paper we provide an overview of benign and malignant osteogenic bone
      tumors. We describe the diagnostic features, radiographic findings, and pertinent
      ancillary studies needed to diagnose these bone-forming lesions. We begin with
      osteoid osteoma and osteoblastoma, which are histologically bland and eminently
      benign with rare possible exceptions. On the other end of the behavioral spectrum
      is osteosarcoma, which encompasses many subtypes ranging from high-grade
      osteogenic osteosarcoma to less overtly osteogenic lesions such as telangiectatic
      and small cell osteosarcoma. While classic osteogenic osteosarcoma can be easily
      recognized by its high grade morphology and formation of extracellular lace-like
      osteoid, its variants may pose diagnostic dilemmas as their differential
      diagnoses can include benign, fibrous, and vascular lesions, among others.
      Recognition of these variants is essential to avoid diagnostic pitfalls. In
      equivocal cases, some forms of osteosarcoma have shown molecular alterations that
      may prove diagnostically useful. 

PMID- 24680180
TI  - Vascular tumors of bone.
AB  - Vascular tumors of the bone represent a variety of neoplasms, ranging from benign
      hemangiomas and epithelioid hemangiomas to intermediate grade
      hemangioendotheliomas to frankly malignant angiosarcomas. Over the years, there
      has been considerable debate concerning the aggressivity, nomenclature, and mere
      existence of various nosologic entities, due to morphologic similarities and
      uncertainty regarding biologic behavior. Such debate has led to confusion among
      pathologists and clinicians, thus diminishing the prognostic implications in the
      diagnosis of these lesions. Here we review the current knowledge concerning the
      primary vascular neoplasms of the bone and correlate clinicopathologic features
      with tumor behavior. 

PMID- 24680181
TI  - Ewing sarcoma.
AB  - Classification of small round cell tumors of bone is often challenging due to
      overlapping clinicopathologic features. The purpose of this article is to review
      the clinical, radiological, histologic, and molecular features of Ewing sarcoma
      and to provide a discussion of the differential diagnosis of small round cell
      tumors of bone. 

PMID- 24680182
TI  - Primary lymphoma of bone: a review.

PMID- 24680183
TI  - Metastases to bones.
AB  - Metastatic tumors involving the bones may derive from a number of visceral
      primary sites, and they can assume several histological appearances. In selected
      instances, diagnostic confusion with some primary bone tumors may eventuate,
      necessitating the use of adjunctive pathologic studies to reach a final
      interpretation. This review considers metastatic osseous neoplasms in the small
      cell, large-polygonal-cell, and spindle-cell-pleomorphic microscopic categories.
      The use of immunohistology and molecular analysis to study such tumors is
      discussed. 

PMID- 24680184
TI  - Proliferative, reparative, and reactive benign bone lesions that may be confused
      diagnostically with true osseous neoplasms.
AB  - Diagnostic problems attending intraosseous and parosteal pseudoneoplastic lesions
      can be radiographic, or histological, or both. Proliferations in this category
      may contain cellular fibro-osseous or chondro-osseous tissues that are difficult
      to separate microscopically from those seen in various true neoplasms of the
      bones. This review considers the clinicopathologic features of fibrous dysplasia,
      benign fibro-osseous lesions of the jawbones, osteofibrous dysplasia, metaphyseal
      fibrous defect, giant-cell reparative granuloma, "brown tumor" of
      hyperparathyroidism, synovial chondrometaplasia, aneurysmal bone cyst,
      tumefactive chronic osteomyelitis, proliferative Paget disease, and
      polyvinylpyrrolidone storage disease of bone.

PMID- 24680185
TI  - Exposure of natural rubber to personal lubricants--swelling and stress relaxation
      as potential indicators of reduced seal integrity of non-lubricated male condoms.
AB  - BACKGROUND: Male condoms act as mechanical barriers to prevent passage of body
      fluids. For effective use of condoms the mechanical seal is also expected to
      remain intact under reasonable use conditions, including with personal
      lubricants. Absorption of low molecular weight lubricant components into the
      material of male condoms may initiate material changes leading to swelling and
      stress relaxation of the polymer network chains that could affect performance of
      the sealing function of the device. Swelling indicates both a rubber-solvent
      interaction and stress relaxation, the latter of which may indicate and/or result
      in a reduced seal pressure in the current context. METHODS: Swelling and stress
      relaxation of natural rubber latex condoms were assessed in a laboratory model in
      the presence of silicone-, glycol-, and water-based lubricants. RESULTS: Within
      15 minutes, significant swelling (>=6 %) and stress reduction (>=12 %) of condoms
      were observed with 2 out of 4 silicone-based lubricants tested, but neither was
      observed with glycol- or water-based lubricants tested. Under a given strain,
      reduction in stress was prominent during the swelling processes, but not after
      the process was complete. CONCLUSIONS: Lubricant induced swelling and stress
      relaxation may loosen the circumferential stress responsible for the mechanical
      seal. Swelling and stress relaxation behavior of latex condoms in the presence of
      personal lubricants may be useful tests to identify lubricant-rooted changes in
      condom-materials. IMPLICATION: For non-lubricated latex condoms, material
      characteristics--which are relevant to failure--may change in the presence of a
      few silicone-based personal lubricants. These changes may in turn induce a loss
      of condom seal during use, specifically at low strain conditions.

PMID- 24680186
TI  - [The annual Plastic and @esthetic surgery report, the internationally oriented
      Annals].

PMID- 24680187
TI  - Elizabethkingia meningoseptica: an important emerging pathogen causing healthcare
      associated infections.
AB  - Elizabethkingia meningoseptica has been deemed a potentially important threat to
      patients in critical care areas because of its multidrug-resistant phenotype and
      its ability to adapt to various environments. This review considers the
      incidence, factors which predispose to, and clinical features of, E.
      meningoseptica sepsis, along with antimicrobial susceptibility patterns of
      clinical E. meningoseptica isolates and reportedly successful measures for the
      prevention and control of infections caused by this bacterium. The English
      language literature from the PubMed database was reviewed. The incidence of E.
      meningoseptica bacteraemia has increased over the last decade. Patients at high
      risk of E. meningoseptica infection include preterm children, the
      immunocompromised and those exposed to antibiotics in critical care units.
      Vancomycin, rifampicin, newer fluoroquinolones, piperacillin-tazobactam,
      minocycline and possibly tigecycline are preferred empirical choices for E.
      meningoseptica infection according to in-vitro susceptibility data. Combination
      therapy has been used for infections not responding to single agents. Saline,
      lipid, and chlorhexidine gluconate solutions as well as contaminated sinks have
      been implicated as sources of infection following outbreak investigations. In
      addition to reinforcement of standard infection control measures, actions that
      have successfully terminated E. meningoseptica outbreaks include pre-emptive
      contact isolation, systematic investigations to identify the source of the
      bacterium and thorough cleaning of equipment and environmental surfaces. As the
      clinical complexity and incidence of E. meningoseptica infections increase, there
      is a need for heightened awareness of the potential for this bacterium to cause
      outbreaks. This will permit timely initiation of active surveillance for
      infected/colonized patients as well as investigations to identify the likely
      source of the bacterium, which will, in turn, allow implementation of appropriate
      infection control measures. 

PMID- 24680188
TI  - Adaptation of machine translation for multilingual information retrieval in the
      medical domain.
AB  - OBJECTIVE: We investigate machine translation (MT) of user search queries in the
      context of cross-lingual information retrieval (IR) in the medical domain. The
      main focus is on techniques to adapt MT to increase translation quality; however,
      we also explore MT adaptation to improve effectiveness of cross-lingual IR.
      METHODS AND DATA: Our MT system is Moses, a state-of-the-art phrase-based
      statistical machine translation system. The IR system is based on the BM25
      retrieval model implemented in the Lucene search engine. The MT techniques
      employed in this work include in-domain training and tuning, intelligent training
      data selection, optimization of phrase table configuration, compound splitting,
      and exploiting synonyms as translation variants. The IR methods include
      morphological normalization and using multiple translation variants for query
      expansion. The experiments are performed and thoroughly evaluated on three
      language pairs: Czech-English, German-English, and French-English. MT quality is
      evaluated on data sets created within the Khresmoi project and IR effectiveness
      is tested on the CLEF eHealth 2013 data sets. RESULTS: The search query
      translation results achieved in our experiments are outstanding - our systems
      outperform not only our strong baselines, but also Google Translate and Microsoft
      Bing Translator in direct comparison carried out on all the language pairs. The
      baseline BLEU scores increased from 26.59 to 41.45 for Czech-English, from 23.03
      to 40.82 for German-English, and from 32.67 to 40.82 for French-English. This is
      a 55% improvement on average. In terms of the IR performance on this particular
      test collection, a significant improvement over the baseline is achieved only for
      French-English. For Czech-English and German-English, the increased MT quality
      does not lead to better IR results. CONCLUSIONS: Most of the MT techniques
      employed in our experiments improve MT of medical search queries. Especially the
      intelligent training data selection proves to be very successful for domain
      adaptation of MT. Certain improvements are also obtained from German compound
      splitting on the source language side. Translation quality, however, does not
      appear to correlate with the IR performance - better translation does not
      necessarily yield better retrieval. We discuss in detail the contribution of the
      individual techniques and state-of-the-art features and provide future research
      directions.

PMID- 24680189
TI  - Cryopreserved dentin matrix as a scaffold material for dentin-pulp tissue
      regeneration.
AB  - Cryopreservation has been identified as an efficient approach to preserve tissue
      engineered products for a long term. Our prior studies have suggested that the
      treated dentin matrix (TDM) could be an ideal bioactive scaffold for dental
      tissue regeneration. In this study, we hypothesize that the cryopreservation
      could effectively maintain the survival and viability of dentinogenesis-related
      proteins of TDM and the cryopreserved dentin matrix (CDM) would provide the
      suitable biological scaffold and inductive microenvironment for the regeneration
      of dentin-pulp like tissue. CDM-3 and CDM-6 were prepared by cryopreserving TDM
      in liquid nitrogen (-196  degrees C) with cryoprotectant for 3 months and 6
      months, respectively. Various biological characteristics of CDM, including
      mechanical properties, cell proliferation, and odontogenesis ability, were
      investigated. To further evaluate the inductive capacity of CDM, human dental
      follicle cells were encapsulated within CDM, and implanted the scaffold into a
      mouse model for 8 weeks, and the grafts were harvested and assessed
      histologically. The CDM showed superior mechanical properties than TDM. Compared
      to TDM, CDM can release more dentinogenesis-related proteins due to the larger
      pore diameter. Cell proliferation with the addition of CDM extract liquid was
      similar to that of TDM in the first five days. Human dental follicle cells, under
      the effect of CDM extract liquid, highly expressed bone sialoprotein, collagen-1,
      alkaline phosphatase, indicating that CDM, regarded as the inductive
      microenvironment, plays an important role in odontogenesis. Most importantly, in
      vivo, CDM could induce dental follicle cells to regenerate new dentin-pulp like
      tissues, such as dentinal tubules, predentin, collagen fibers, nerves, and blood
      vessels which were positive for dentin sialophosphoprotein, dental matrix protein
      1, Tubulin, and collagen-1. In conclusion, CDM is an ideal biological scaffold
      material for human dentin-pulp like tissue regeneration. These findings indicated
      that TDM could be preserved as the tissue engineering scaffold that is readily
      available for patient treatments. Furthermore, the success of cryopreservation of
      TDM may also provide an insight into preserving other bioactive scaffold
      materials of tissue engineering. 

PMID- 24680191
TI  - Synergistic inhibition of breast cancer by co-delivery of VEGF siRNA and
      paclitaxel via vapreotide-modified core-shell nanoparticles.
AB  - A somatostatin analog, vapreotide (VAP), can be used as a ligand for targeting
      drug delivery based on its high affinity to somatostatin receptors (SSTRs), which
      is overexpressed in many tumor cells. RNA interference plays an important role on
      downregulation of vascular endothelial growth factor (VEGF), which is important
      for tumor growth, progression and metastasis. To improve tumor therapy efficacy,
      the vapreotide-modified core-shell type nanoparticles co-encapsulating VEGF
      targeted siRNA (siVEGF) and paclitaxel (PTX), termed as VAP-PLPC/siRNA NPs, were
      developed in this study. When targeted via somatostatin receptors to tumor cells,
      the VAP-PLPC/siRNA NPs could simultaneously delivery siVEGF and PTX into cells
      and achieve a synergistic inhibition of tumor growth. Interestingly, in vitro
      cell uptake and gene silencing experiments demonstrated that the targeted VAP
      PLPC/siRNA NPs exhibited significant higher intracellular siRNA accumulation and
      VEGF downregulation in human breast cancer MCF-7 cells, compared to those of the
      non-targeted PEG-PLPC/siRNA NPs. More importantly, in vivo results further
      demonstrated that the targeted VAP-PLPC/siRNA NPs had significant stronger drug
      distribution in tumor tissues and tumor growth inhibition efficacy via receptor
      mediated targeting delivery, accompany with an obvious inhibition of
      neovascularization induced by siVEGF silencing. These results suggested that the
      co-delivery of siRNA and paclitaxel via vapreotide-modified core-shell
      nanoparticles would be a promising approach for tumor targeted therapy.

PMID- 24680190
TI  - Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose
      derived cells.
AB  - The major problem in skin grafting is that tissue-engineered skin grafts after
      their transplantation are initially entirely dependent on diffusion. Since this
      process is slow and inefficient, nutrients, growth factors, and oxygen will
      insufficiently be supplied and the regenerating graft will undergo a
      physiological crisis, resulting in scar-like dermal structures and shrinkage. The
      tissue-engineering of a vascular network in human dermo-epidermal skin
      substitutes (DESS) is a promising approach to overcome this limitation. Here we
      report, for the first time, on the use of the adipose stromal vascular fraction
      (SVF)-derived endothelial cell population to tissue-engineer DESS containing a
      highly efficient capillary plexus. To develop vascular networks in vitro, we
      employed optimized 3D fibrin or collagen type I hydrogel systems. Upon
      transplantation onto immune-deficient rats, these pre-formed vascular networks
      anastomosed to the recipient's vasculature within only four days. As a
      consequence, the neo-epidermis efficiently established tissue homeostasis, the
      dermis underwent almost no contraction, and showed sustained epidermal coverage
      in vivo. Overall, the here described rapid and efficient perfusion of SVF-based
      skin grafts opens new perspectives for the treatment of hitherto unmet clinical
      needs in burn/plastic surgery and dermatology.

PMID- 24680193
TI  - Multibit data storage states formed in plasma-treated MoS2 transistors.
AB  - New multibit memory devices are desirable for improving data storage density and
      computing speed. Here, we report that multilayer MoS2 transistors, when treated
      with plasmas, can dramatically serve as low-cost, nonvolatile, highly durable
      memories with binary and multibit data storage capability. We have demonstrated
      binary and 2-bit/transistor (or 4-level) data states suitable for year-scale data
      storage applications as well as 3-bit/transistor (or 8-level) data states for day
      scale data storage. This multibit memory capability is hypothesized to be
      attributed to plasma-induced doping and ripple of the top MoS2 layers in a
      transistor, which could form an ambipolar charge-trapping layer interfacing the
      underlying MoS2 channel. This structure could enable the nonvolatile retention of
      charged carriers as well as the reversible modulation of polarity and amount of
      the trapped charge, ultimately resulting in multilevel data states in memory
      transistors. Our Kelvin force microscopy results strongly support this
      hypothesis. In addition, our research suggests that the programming speed of such
      memories can be improved by using nanoscale-area plasma treatment. We anticipate
      that this work would provide important scientific insights for leveraging the
      unique structural property of atomically layered two-dimensional materials in
      nanoelectronic applications. 

PMID- 24680192
TI  - Danish version of the Tilburg Frailty Indicator--translation, cross-cultural
      adaption and validity pretest by cognitive interviewing.
AB  - The Tilburg Frailty Indicator (TFI) is a self-administered questionnaire with a
      bio-psycho-social integrated approach that measures the degree of frailty in
      elderly persons. The TFI was developed in the Netherlands and tested in a
      population of elderly Dutch men and women. The aim of this study was to translate
      and culturally adapt the TFI to a Danish context, and to test face validity of
      the Danish version by cognitive interviewing. An internationally recognized
      procedure was applied as a basis for the translation process. The primary tasks
      were forward translation, reconciliation, back translation, harmonization and
      pretest. Pretest and review of the preliminary version by cognitive interviewing,
      were performed at a local community center and in an acute medical ward at the
      University Hospital in Aalborg, Denmark respectively. A large agreement regarding
      meaning of the items in the forward translation and reconciliation process was
      seen. Minor discrepancies were solved by consensus. Back translation revealed
      unclear wording in one matter. The harmonization committee agreed on a version
      for cognitive interviewing after revision of minor issues and thirty-four
      participants were interviewed. Two issues became evident and these were revised.
      The cognitive interviews and final lay-out resulted in minor adjustments as text
      type size, specific font, and lining for optimizing readability. In conclusion,
      we consider the TFI to be translated in such rigorous manner that the instrument
      can be further tested in clinical practice. The overall objective of the
      questionnaire being to identify frailty and improve the interventions relating to
      frail elderly persons in Denmark. 

PMID- 24680194
TI  - Improving bovine semen diluents: insights from the male and female reproductive
      tracts, and the potential relevance of cervical mucins.
AB  - The commercial applicability of bovine artificial insemination (AI) depends on
      the effectiveness of diluents for maintaining sperm fertility. Challenges faced
      by the AI industry due to recent advances in assisted reproduction, and the
      limitations inherent in using fresh and frozen-thawed sperm for AI, could be
      overcome with the development of better semen diluents. Research into the
      different microenvironments of bovine sperm as they progress towards maturity,
      capacitation and fertilisation is revealing various mechanisms that could be
      exploited to improve the formulation of semen diluents. These are reviewed here.
      A rationale for a more detailed investigation of bovine cervical mucus for
      factors that may allow further progress towards this goal are also discussed. 

PMID- 24680195
TI  - Clinical instructors' knowledge and perceptions about nursing care of older
      people: a pilot study.
AB  - With an aging population, the majority of nurses will spend their careers working
      with older people. Currently, there is scant research about clinical instructors'
      knowledge and perceptions about nursing care of older people despite their
      instrumental role in preparing nurses for practice. The purpose of this study was
      to explore clinical instructors' knowledge and perceptions about nursing care of
      older people. A mixed methods approach was used. Fifteen clinical instructors and
      15 nurse educators employed on specialized units for older people completed
      questionnaires. Independent t-tests were administered. Five of the clinical
      instructors also participated in semi-structured interviews, which were analyzed
      using thematic analysis. Findings indicated that clinical instructors had
      significantly lower scores on knowledge and perceptions about nursing care of
      older people than practice-based nurse educators. Further, clinical instructors
      found it difficult to integrate specialized knowledge about nursing care of older
      people along with other aspects of their teaching. They also reported that it was
      challenging to support learning about best practices for older people within the
      current clinical context, which was complex and fast-paced. This study reinforces
      the need for professional development opportunities for clinical instructors to
      support their instrumental role in preparing students for practice with older
      people. 

PMID- 24680196
TI  - Of thresholds and "hot spots". Quo vadis transcranial magnetic stimulation?

PMID- 24680198
TI  - Maternal choline supplementation: a nutritional approach for improving offspring
      health?
AB  - The modulatory role of choline on the fetal epigenome and the impact of in utero
      choline supply on fetal programming and health are of great interest. Studies in
      animals and/or humans suggest that maternal choline supplementation during
      pregnancy benefits important physiologic systems such as offspring cognitive
      function, response to stress, and cerebral inhibition. Because alterations in
      offspring phenotype frequently coincide with epigenetic modifications and changes
      in gene expression, maternal choline supplementation may be a nutritional
      strategy to improve lifelong health of the child. Future studies are warranted to
      elucidate further the effect of choline on the fetal epigenome and to determine
      the level of maternal choline intake required for optimal offspring physiologic
      function. 

PMID- 24680197
TI  - Asymmetries in vestibular evoked myogenic potentials in chronic stroke survivors
      with spastic hypertonia: evidence for a vestibulospinal role.
AB  - OBJECTIVE: Indirect evidence suggests that lateralized changes in motoneuron
      behavior post-stroke are potentially due to a depolarizing supraspinal drive to
      the motoneuron pool, but the pathways responsible are unknown. In this study, we
      assessed vestibular evoked myogenic potentials (VEMPs) in the neck muscles of
      hemispheric stroke survivors with contralesional spasticity to quantify the
      relative levels of vestibular drive to the spastic-paretic and contralateral
      motoneuron pools. METHODS: VEMPs were recorded from each sternocleidomastoid
      muscle in chronic stroke survivors. Side-to-side differences in cVEMP amplitude
      were calculated and expressed as an asymmetry ratio, a proxy for the relative
      amount of vestibular drive to each side. RESULTS: Spastic-paretic VEMPs were
      larger than contralateral VEMPs in 13/16 subjects. There was a strong positive
      relationship between the degree of asymmetry and the severity of spasticity in
      this subset of subjects. Remaining subjects had larger contralateral responses.
      CONCLUSION: Vestibular drive to cervical motoneurons is asymmetric in spastic
      stroke survivors, supporting our hypothesis that there is an imbalance in
      descending vestibular drive to motoneuron pools post-stroke. We speculate this
      imbalance is a consequence of the unilateral disruption of inhibitory
      corticobulbar projections to the vestibular nuclei. SIGNIFICANCE: This study
      sheds new light on the underlying mechanisms of post-stroke spasticity.

PMID- 24680199
TI  - [Infanticides in France: can they be identified, counted, and prevented?].

PMID- 24680200
TI  - [Breastfeeding in the French-speaking community of Belgium (2009)].
AB  - PURPOSE: The objectives of this paper were to study the prevalence of
      breastfeeding in the French-speaking community of Belgium, to assess whether the
      targets of the Maternal and Child Health program (MCH) were met (prevalence of
      breastfeeding of 85, 70, 50, and 25% at the maternity hospital and at 3, 6, and
      12 months of age, respectively), and to identify factors associated with
      breastfeeding at the maternity hospital and at 6 months of age. MATERIALS AND
      METHODS: A sample (two-stage cluster sampling) was drawn from the population of
      children aged 18-24 months living in the area. A face-to-face questionnaire was
      administered by trained investigators. Anamnestic data on breastfeeding at the
      maternity hospital and at 3, 6, and 12 months as well sociodemographic
      information were collected from 522 mothers. The survey took place in 2009.
      RESULTS: At the maternity hospital, 75.7% (95%CI [72.7-79.5]) of the mothers were
      breastfeeding: 72.4% among the Belgians (and French) and 89.0% among foreign
      mothers. At 3 months of age, the breastfeeding prevalence was 48.3% (CI, 44.0
      52.6): 42.5% among the Belgians (and French) and 72.0% among foreign mothers
      (p<0.001). At 6 months of age, 26.0% of the mothers were breastfeeding (CI, 22.3
      29.8): 19.3% among the Belgians (and French) and 53.0% among foreign mothers
      (p<0.001). At 12 months of age, 10.0% (CI, 7.4-12.5) of the mothers were
      breastfeeding: 4.8% among the Belgians (and French) and 31.0% among the foreign
      mothers (p<0.001). When fitting a logistic model, the predictors associated with
      breastfeeding at the maternity hospital were educational level, nationality of
      birth, and parity. At 6 months, logistic models were fitted separately in the two
      strata. Among the Belgians, the level of education and attending a MCH
      consultation were significantly associated with breastfeeding. In the stratum of
      foreign mothers, the only factor associated with breastfeeding was working time.
      No association was observed between breastfeeding and the mother's age at the
      maternity hospital or at 6 months. DISCUSSION: The targets of the MCH were not
      reached in Belgian and French mothers, while they were in mothers of other
      nationalities. Until now, transversal surveys have been the only way of knowing
      the prevalence and the factors associated with breastfeeding in the French
      speaking community of Belgium. These first representative data on breastfeeding
      came from the 2009 vaccine coverage survey.

PMID- 24680201
TI  - [Judicial decisions after reporting cases of shaken baby syndrome. Sentences and
      compensation].
AB  - BACKGROUND: Shaken baby syndrome (SBS) is defined by the association of
      intracranial hemorrhage and retinal hemorrhage in infants under 2 years of age,
      with no obvious external trauma. This syndrome leads to frequent neurological
      sequelae. Therefore, these infants can claim compensation for damage if sequelae
      are directly and irrefutably linked to the trauma. Data on the judicial treatment
      are for the most part inexistent in the medical literature, the reason for which
      this study was conducted. POPULATION AND METHODS: We conducted a retrospective
      study over a period of 10 years. We included all cases of SBS reported to the
      High Courts of the Ille-et-Vilaine department (Rennes and St Malo). The cases
      were listed from the archives of the Department of Medical Information, the
      Specialized Unit for Abused Children and Forensic Department at the Rennes
      University Hospital. We were able to look the judicial cases up after receiving
      agreement from the prosecutors of the two courts. RESULTS: Of the 34 cases
      included, 12 could not be used (lost, ongoing, destroyed, transferred to another
      court), 16 led to an order of dismissal or to no further action because of an
      unknown perpetrator, insufficiently described offense, or insufficient evidence.
      Six authors were sentenced. It was the father (n=5) or the childminder (n=1). All
      perpetrators had confessed to part or all of the charges brought against them.
      Five children received compensation: three by the civil court and two by the
      commission of compensation for victims of an offense. CONCLUSION: Most cases led
      to no conviction and no compensation. The identification by the physician of the
      person responsible for the lesions in SBS does not mean that the perpetrator will
      be convicted because of the strict application of criminal law. The nomination of
      an administrator representing the infant could resolve the lack of compensation.

PMID- 24680202
TI  - Interest of platelet inhibition monitoring in intracranial arterial stenosis
      before stenting.

PMID- 24680203
TI  - E-cigarette prevalence and correlates of use among adolescents versus adults: a
      review and comparison.
AB  - Perceived safer than tobacco cigarettes, prevalence of electronic cigarette (e
      cigarette) use is increasing. Analyses of cartridges suggest that e-cigarettes
      may pose health risks. In light of increased use and the potential for
      consequences, we searched Google Scholar and Pubmed in July of 2013 using
      keywords, such as e-cigarette and vaping, to compare differences and similarities
      in prevalence and correlates of e-cigarette use among adolescents (grades 6-12)
      versus adults (aged >=18 years). Twenty-one studies focused on e-cigarette use.
      Ever-use increased among various age groups. In 2011, ever-use was highest among
      young adults (college students and those aged 20-28; 4.9%-7.0%), followed by
      adults (aged >=18; 0.6%-6.2%), and adolescents (grades 6-12 and aged 11-19; <1%
      3.3%). However, in 2012 adolescent ever-use increased to 6.8% and, among high
      school students, went as high as 10.0%. While the identified common correlate of
      e-cigarette use was a history of cigarette smoking, a notable proportion of
      adolescents and young adults who never smoked cigarettes had ever-used e
      cigarettes. E-cigarette use was not consistently associated with attempting to
      quit tobacco among young adults. Adults most often reported e-cigarettes as a
      substitute for tobacco, although not always to quit. Reviewed studies showed a
      somewhat different pattern of e-cigarette use among young people (new e-cigarette
      users who had never used tobacco) versus adults (former or current tobacco
      users). Research is needed to better characterize prevalences, use correlates,
      and motives of use in different population groups, including how adolescent and
      young adult experimentation with e-cigarettes relates to other types of substance
      use behaviors. 

PMID- 24680204
TI  - Anesthesia and analgesia for standing equine surgery.
AB  - Morbidity and mortality rate in equine anesthesia is still unacceptably high.
      Thus it is critical contemplating whether the benefit of general anesthesia for a
      specific patient and procedure outweighs the risks. Sedative protocols that would
      allow performing diagnostic and surgical procedures with the patient remaining
      standing would therefore be ideal. Infusion of short-acting agents allows to
      rapidly achieve a titratable steady state of sedation. Supplementing sedatives
      and tranquilizers with systemic analgesic or regional anesthetic techniques (i.e.
      epidurals) facilitates standing surgical procedures. Multimodal analgesia would
      also provide superior analgesia with potentially fewer side effects than a single
      agent approach. 

PMID- 24680205
TI  - Advances in laparoscopic techniques and instrumentation in standing equine
      surgery.
AB  - Equine standing surgery and laparoscopy are becoming increasingly important
      aspects of equine surgery. Laparoscopic advancements lag behind the human medical
      field, mainly due to decreased access to appropriate training and
      instrumentation. It is nearly impossible to cover the topic of equine standing
      surgery without discussing advances in laparoscopy, because without such
      advances, equine standing surgery lacks potential for forward progress. Although
      novel standing techniques continue to be published, the addition of minimally
      invasive laparoscopic techniques adds an entirely new dimension and provides a
      plethora of procedures to surgeons practicing equine standing surgery. 

PMID- 24680206
TI  - Standing equine sinus surgery.
AB  - Trephination of the equine sinuses is a common surgical procedure in sedated
      standing horses. Standing sinus flap surgery has become increasingly popular in
      equine referral hospitals and offers several advantages over sinusotomy performed
      under general anesthesia, including reduced patient-associated risks and costs;
      less intraoperative hemorrhage, allowing better visualization of the operative
      site; and allows surgeons to take their time. Other minimally invasive surgical
      procedures include sinoscopic surgery, balloon sinuplasty, and transnasal laser
      sinonasal fenestration. Despite the procedure used, appropriate indications for
      surgery, good patient selection, and familiarity with regional anatomy and
      surgical techniques are imperative for good results. 

PMID- 24680207
TI  - Standing equine dental surgery.
AB  - Dental surgeries refer to procedures that affect the dental tissues or their
      supporting structures. With the development of specific, efficacious, and
      conservative treatments, morbidity risks have been lowered and chances of
      benefiting the health of equids improved. Advances in quality of sedation,
      analgesia, and locoregional anesthesia allow a majority of dental surgeries to be
      performed in the standing patient. This update focuses on an orthograde
      endodontic technique, a minimally invasive buccotomy technique, with the
      potential to combine it with a transbuccal screw extraction technique, and
      revisits the AO pinless external fixator for fractures of the body of the
      mandible. 

PMID- 24680208
TI  - Standing ophthalmic surgeries in horses.
AB  - Standing ophthalmic surgery without general anesthesia allows for several routine
      ophthalmic procedures including eyelid lacerations and enucleations to be
      performed in the horse, but does contain increased risk of causing tissue damage
      arising from the inability to eliminate eye and head movements. Heavy sedation
      and local nerve blocks of the involved motor and sensory nerves are essential in
      achieving a good outcome from ophthalmic surgery in the nonanesthetized horse.
      The inability to use an operating microscope in standing surgery in horses
      prevents performing precise corneal and intraocular microsurgeries. 

PMID- 24680209
TI  - Standing equine surgery of the upper respiratory tract.
AB  - The purpose of this article is to review the literature and personal experiences
      of equine surgeons so as to describe procedures that can be performed in the
      standing sedated horse to alleviate conditions that result in upper respiratory
      tract obstruction. Upper respiratory tract surgery requires attention to detail,
      meticulous planning, and careful dissection and execution with little room for
      error. This article describes a selection of standing upper airway procedures,
      the indications for and possible complications of these surgeries, and advantages
      and disadvantages of a particular method. 

PMID- 24680210
TI  - Standing diagnostic and therapeutic equine abdominal surgery.
AB  - The widespread use of laparoscopy in equine surgery has increased interest in the
      standing approach to a wide range of procedures typically regarded as feasible
      only through a ventral midline incision. Although a commonly cited benefit of
      standing surgery relates to avoiding costs of general anesthesia and risks
      associated with it, some procedures and horses are not suitable candidates for
      standing abdominal procedures. Some procedures, such as nephrectomy, colostomy,
      and closure of the nephrosplenic space, are not only suitable for standing
      surgery but are performed more easily and more safely through this approach than
      with general anesthesia. 

PMID- 24680211
TI  - Standing male equine urogenital surgery.
AB  - The advantages of performing standing male urogenital surgeries are numerous when
      compared with performing the same surgery in the anesthetized animal. Some
      traditional standing male urogenital surgeries, such as castrations, may be
      faster and cheaper to perform. Laparoscopic standing male urogenital surgeries
      may allow for improved visualization of the surgical field, decreased hemorrhage,
      and decreased morbidity and convalescence. Limitations of standing procedures may
      include increased danger to the surgeon because of fractious behavior of the
      patient, and increased expense and training associated with instrumentation for
      specialized procedures such as laparoscopy. 

PMID- 24680212
TI  - Urogenital surgery performed with the mare standing.
AB  - Many urogenital procedures of the mare are commonly performed with the mare
      standing. Ovariectomy via colpotomy was described as early as 1903, and the
      Caslick vulvoplasty was first described in 1937. As knowledge expands and
      instruments become more specialized, techniques will improve. With the
      introduction of laparoscopy, clinicians have not only been able to improve the
      previously described urogenital procedures but also to devise new procedures.
      This article describes multiple surgeries of the female urogenital tract, all of
      which can be performed with the mare standing, and describes a variety of
      approaches to some portions of the female urogenital tract.

PMID- 24680213
TI  - Diagnostic and therapeutic arthroscopy in the standing horse.
AB  - This article describes diagnostic arthroscopy and arthroscopic management of
      selected lesions in the standing equine patient. Details on case selection,
      patient and operating room preparation, and surgical technique are presented.
      This information will add techniques that avoid general anesthesia to the equine
      surgeon's armamentarium. 

PMID- 24680214
TI  - Recent advances in standing equine orthopedic surgery.
AB  - In all surgeries with the patient standing under chemical and physical restraint,
      patient compliance is of the utmost importance. All fractures of the third
      metacarpal or metatarsal condyles and sagittal fracture of the first phalanx are
      not amenable to internal fixation with the horse standing, and young unhandled
      horses may not have a suitable disposition for standing surgical treatment of
      septic pedal osteitis, or implantation and removal of transphyseal screws.
      Previous operator experience in performing the procedure or technique under
      general anesthesia is beneficial. Appreciation of appropriate topographic
      anatomic landmarks is important, and intraoperative radiographic control is
      useful. 

PMID- 24680215
TI  - New concepts in standing advanced diagnostic equine imaging.
AB  - This article addresses the clinical application of magnetic resonance imaging
      (MRI) and computed tomography (CT) as applied to the standing equine patient.
      This discussion includes the logistics, advantages, disadvantages, and
      limitations of imaging a standing horse. In addition, a brief review is given of
      the physics of these modalities as applied in clinical practice, and the
      currently available hardware and software required by these techniques for image
      acquisition and artifact reduction. The appropriate selection of clinical cases
      for standing MRI and CT is reviewed, focusing on cases that are capable of
      undergoing standing surgeries following lesion diagnosis. 

PMID- 24680216
TI  - Standing surgery. Preface.

PMID- 24680217
TI  - Topographical and drug specific sensitivity of hair cells of the zebrafish larvae
      to aminoglycoside-induced toxicity.
AB  - The hair cells of the lateral line system of fishes are morphologically and
      physiologically similar to the hair cells of the mammalian inner ear, also
      sharing its molecular characteristics. For this reason, it has been used as a
      powerful animal model to analyze in vivo ototoxicity. In this work, we examined
      the dose-dependent effects of two potent ototoxic aminoglycosides, neomycin and
      gentamicin, on the hair cells of two selected neuromasts (L1 and T1, the first of
      the trunk and the terminal located in the fin, respectively) of the lateral line
      in the ET4 transgenic zebrafish line. The hair cells of this strain selectively
      and constitutively display fluorescence. The fish were treated for 24 h at
      different doses (1, 2.5, 5, 10 and 100 MUM levels) of both aminoglycosides.
      Immediately after treatment the morphology and the number of cells in L1 and T
      were analyzed under a fluorescence microscope. The results show that neomycin and
      gentamicin have different effects on the hair cell death at the same
      concentration, showing also different toxicity in L1 and T1 neuromasts. The
      toxicity observed in the hair cells of T1 neuromast was less than in L1
      especially for the gentamicin treatment. These results demonstrate different
      sensitivity of hair cells of the lateral line to ototoxic drugs according to
      topographical localization and suggest the in vivo assay of the L1 neuromast of
      zebrafish larva and low doses of neomycin as an ideal model to study ototoxicity
      induced by aminoglycosides.

PMID- 24680218
TI  - Substance-abusing mothers and fathers' willingness to allow their children to
      receive mental health treatment.
AB  - The purpose of this study was to examine attitudes of substance-abusing mothers
      and fathers entering outpatient treatment toward allowing their children to
      participate in individual- or family-based interventions. Data were collected
      from a brief anonymous survey completed by adults at intake into a large
      substance abuse treatment program in western New York. Only one-third of parents
      reported that they would be willing to allow their children to participate in any
      form of mental health treatment. Results of chi-square analyses revealed that a
      significantly greater proportion of mothers reported that they would allow their
      children to participate in mental health treatment (41%) compared to fathers
      (28%). Results of logistic regression analyses revealed even after controlling
      for child age, mothers were more likely than fathers to indicate their
      willingness to allow their children to receive mental health treatment; however,
      type of substance abuse (alcohol versus drug abuse) was not associated with
      parents' willingness to allow their children to receive treatment. Parental
      reluctance to allow their children to receive individual or family-based
      treatment is a significant barrier in efforts to intervene with these at-risk
      children. 

PMID- 24680219
TI  - Abuse and diversion of buprenorphine sublingual tablets and film.
AB  - Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three
      sublingual buprenorphine formulations (single ingredient tablets; naloxone
      combination tablets and film) were compared. Data were obtained from the
      Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System
      Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants'
      Patients (SKIP), and College Survey Programs through December 2012. To control
      for drug availability, event ratios (rates) were calculated quarterly, based on
      the number of patients filling prescriptions for each formulation ("unique
      recipients of a dispensed drug," URDD) and averaged and compared using negative
      binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs
      were greatest for single ingredient tablets, and abuse rates in the Poison Center
      Program and illicit diversion rates were greatest for the combination tablets.
      Combination film rates were significantly less than rates for either tablet
      formulation in all programs. No geographic pattern could be discerned.

PMID- 24680220
TI  - One ring to bring them all--the role of Ku in mammalian non-homologous end
      joining.
AB  - The repair of DNA double strand breaks is essential for cell survival and several
      conserved pathways have evolved to ensure their rapid and efficient repair. The
      non-homologous end joining pathway is initiated when Ku binds to the DNA break
      site. Ku is an abundant nuclear heterodimer of Ku70 and Ku80 with a toroidal
      structure that allows the protein to slide over the broken DNA end and bind with
      high affinity. Once locked into placed, Ku acts as a tool-belt to recruit
      multiple interacting proteins, forming one or more non-homologous end joining
      complexes that act in a regulated manner to ensure efficient repair of DNA ends.
      Here we review the structure and functions of Ku and the proteins with which it
      interacts during non-homologous end joining. 

PMID- 24680221
TI  - Cytolethal distending toxin (CDT) is a radiomimetic agent and induces persistent
      levels of DNA double-strand breaks in human fibroblasts.
AB  - Cytolethal distending toxin (CDT) is a unique genotoxin produced by several
      pathogenic bacteria. The tripartite protein toxin is internalized into mammalian
      cells via endocytosis followed by retrograde transport to the ER. Upon
      translocation into the nucleus, CDT catalyzes the formation of DNA double-strand
      breaks (DSBs) due to its intrinsic endonuclease activity. In the present study,
      we compared the DNA damage response (DDR) in human fibroblasts triggered by
      recombinant CDT to that of ionizing radiation (IR), a well-known DSB inducer.
      Furthermore, we dissected the pathways involved in the detection and repair of
      CDT-induced DNA lesions. qRT-PCR array-based mRNA and western blot analyses
      showed a partial overlap in the DDR pattern elicited by CDT and IR, with strong
      activation of both the ATM-Chk2 and the ATR-Chk1 axis. In line with its in vitro
      DNase I-like activity on plasmid DNA, neutral and alkaline Comet assay revealed
      predominant induction of DSBs in CDT-treated fibroblasts, whereas irradiation of
      cells generated higher amounts of SSBs and alkali-labile sites. Using confocal
      microscopy, the dynamics of the DSB surrogate marker gamma-H2AX was monitored
      after pulse treatment with CDT or IR. In contrast to the fast induction and
      disappearance of gamma-H2AX-foci observed in irradiated cells, the number of
      gamma-H2AX-foci induced by CDT were formed with a delay and persisted. 53BP1 foci
      were also generated following CDT treatment and co-localized with gamma-H2AX
      foci. We further demonstrated that ATM-deficient cells are very sensitive to CDT
      induced DNA damage as reflected by increased cell death rates with concomitant
      cleavage of caspase-3 and PARP-1. Finally, we provided novel evidence that both
      homologous recombination (HR) and non-homologous end joining (NHEJ) protect
      against CDT-elicited DSBs. In conclusion, the findings suggest that CDT functions
      as a radiomimetic agent and, therefore, is an attractive tool for selectively
      inducing persistent levels of DSBs and unveiling the associated cellular
      responses.

PMID- 24680222
TI  - Screening for anal malignancies in men and women.

PMID- 24680223
TI  - The effects of hyperuricaemia on flow-mediated and nitroglycerin-mediated
      dilatation in high-risk patients.
AB  - BACKGROUND AND AIMS: Uric acid is emerging as one of the newer risk markers to
      consider in the cardiovascular risk assessment because it is demonstrated to be
      associated with adverse cardiovascular outcomes, particularly in high
      cardiovascular risk patients. One of the proposed mechanisms involving
      hyperuricaemia is the development of vascular damage. The aim of this study is to
      examine the role of hyperuricaemia on vascular function in patients with high
      cardiovascular risk. METHODS AND RESULTS: We examined the clinical significance
      of hyperuricaemia in relation to vasomotor response of the brachial artery by
      using high-resolution ultrasound in 304 subjects with coronary artery disease
      and/or diabetes. Nitroglycerin-mediated dilatation (NMD) was significantly lower
      in the hyperuricaemic group compared with the normouricaemic group (12.8 +/- 6.9%
      vs. 16.2 +/- 7.7%, p < 0.001), but no significant difference was observed in flow
      mediated dilatation (FMD) between the two groups [3.78 (95% CR: 1.5-9.9) vs. 3.88
      (95% CR: -2.6 to 9.9), p = 0.78]. Multivariate analysis demonstrated that smoking
      was the strongest predictor of FMD (b = -0.81, p = 0.02); and that smoking (b = 
      2.62, p = 0.003), SBP (b = -0.11, p = 0.001), hyperuricaemia (b = -2.11, p =
      0.02) and use of nitrates (b = -3.30, p = 0.001) were independent predictors of
      NMD. CONCLUSION: High cardiovascular risk patients with hyperuricaemia had a
      lower NMD than those with normouricaemia. Importantly, hyperuricaemia was
      independently associated with NMD after multivariable adjustments. To further
      understand the pathophysiological mechanisms involving hyperuricaemia,
      particularly in the context of impaired NMD, further experimental and clinical
      studies are needed.

PMID- 24680224
TI  - Prediction of cardiovascular disease by abdominal obesity measures is dependent
      on body weight and sex--results from two community based cohort studies.
AB  - AIM: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal
      diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men
      and women stratified by BMI (cut-off >=25). METHODS AND RESULTS: A cohort of n =
      3741 (53% women) 60-year old individuals without CVD was followed for 11-years
      (375 CVD cases). To replicate the results, we also assessed another large
      independent cohort; The Malmo Diet and Cancer study - cardiovascular cohort
      (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for
      established risk factors in normal-weight women, the hazard ratio (HR) per one
      standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70),
      WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI
      1.40-2.78). In men the association with WHR, WHHR and WC were not significant,
      whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19
      (95% CI 1.04-1.35). After adjustments for established risk factors in
      overweight/obese women, none of the measures were significantly associated with
      CVD risk. In men, however, all measures were significant predictors; WHR; 1.24
      (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and
      WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI >= 25 were
      verified in MDCC. CONCLUSION: In normal weight individuals, WHHR and WHR were the
      best predictors in women, whereas SAD was the only independent predictor in men.
      Among overweight/obese individuals all measures failed to predict CVD in women,
      whereas WHHR was the strongest predictor after adjustments for CVD risk factors
      in men.

PMID- 24680226
TI  - Rethinking the role of worry in generalized anxiety disorder: evidence supporting
      a model of emotional contrast avoidance.
AB  - The Contrast Avoidance model (Newman & Llera, 2011) proposes that individuals
      with generalized anxiety disorder (GAD) are hypersensitive to sharp upward shifts
      in negative emotion that typically accompany negative events, and use worry to
      maintain sustained intrapersonal negativity in an attempt to avoid these shifts.
      Although research shows that worry increases negative emotionality and mutes
      further emotional reactivity to a stressor when compared to the worry period
      (e.g., Llera & Newman, 2010), no study has tracked changes in negative
      emotionality from baseline to worry inductions followed by a range of emotional
      exposures. Further, no study has yet assessed participants' subjective appraisals
      of prior worry on helping to cope with such exposures. The present study tested
      the main tenets of the Contrast Avoidance model by randomly assigning
      participants with GAD (n=48) and nonanxious controls (n=47) to experience worry,
      relaxation, and neutral inductions prior to sequential exposure to fearful, sad,
      and humorous film clips. Both physiological (nonspecific skin conductance
      responses [NS-SCRs]) and self-reported emotional changes were observed. Results
      indicated that worry boosted negative emotionality from baseline, which was
      sustained across negative exposures, whereas low negative emotionality during
      relaxation and neutral inductions allowed for sharp increases in response to
      exposures. Furthermore, GAD participants found worry to be more helpful than
      other conditions in coping with exposures, whereas control participants reported
      the opposite pattern. Results provide preliminary support for the Contrast
      Avoidance model. This suggests that treatment should focus on underlying
      avoidance patterns before attempting to reduce worry behavior. 

PMID- 24680225
TI  - Flow-mediated dilation, carotid wall thickness and HDL function in subjects with
      hyperalphalipoproteinemia.
AB  - BACKGROUND AND AIMS: The relationships between very high plasma HDLc and
      subclinical atherosclerosis are still a matter of debate. METHODS AND RESULTS:
      Twenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the
      highest 10th percentile and absence of overt secondary causes of this condition),
      aged 30-65 years, were compared with 20 age and sex-matched controls. Lipid
      determination, lipoprotein particle distribution (Lipoprint((r))), Cholesterol
      Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG
      genes and of different markers of subclinical vascular disease (ankle-brachial
      index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated
      dilation, FMD) were performed. Fasting HDLc levels were 40 mg/dl higher in HAL
      subjects while LDLc concentration was comparable to control group. CETP gene
      analysis in HAL subjects identified one novel rare Single Nucleotide Polymorphism
      (SNP, Asp131Asn), possibly damaging, while the common SNP p.Val422Ile was highly
      prevalent (50% vs. 27.4% in a control population). No rare mutations associated
      with HAL were found in SR-B1 and LIPG genes. Polyacrylamide gel electrophoresis
      in HAL subjects disclosed larger and more buoyant HDL particles than in controls,
      while LDL profile was much more similar. ABI, cIMT and arterial plaques did not
      differ in cases and controls and the two groups showed comparable FMD at brachial
      artery examination. Similarly, ABCA1 and ABCG1 HDL-mediated CEC, the most
      relevant for atheroprotection, did not discriminate between the groups and only
      ABCG1 pathway seemed somewhat related to arterial reactivity. CONCLUSIONS: HDL
      dimension, function and genetics seem scarcely related to subclinical
      atherosclerosis and vascular reactivity in middle-aged HAL subjects.

PMID- 24680227
TI  - Extreme nonresponse to acute phase cognitive therapy for depression: an attempt
      to replicate and extend.
AB  - As with other interventions for major depressive disorder (MDD), cognitive
      therapy (CT) results in treatment failure for about half of all participants. In
      2007, Coffman and colleagues in Seattle studied this topic by identifying a group
      of patients who demonstrated an extremely poor response to CT (i.e.,
      posttreatment BDI score>=31). They called these patients "extreme nonresponders"
      (ENR) and described the pretreatment characteristics that predicted response
      status. In the current study, we attempt a replication of the Seattle study with
      a larger sample of adults with recurrent MDD (N=473) who received a 16-20 session
      (12-14week) course of CT. The rate of ENR in this large sample was only 6.3%
      (30/473), compared to 22.2% (10/45) in the Seattle sample. Four pretreatment
      measures of symptom severity and functioning differed significantly among ENR and
      non-ENR participants. In each case, higher symptoms or poorer functioning were
      associated with ENR status. However, the combination of these factors in a
      regression model did not predict actual ENR status with the high degree of
      sensitivity or specificity observed in the Seattle study. These findings suggest
      that extreme nonresponse to CT is not as common as previously described and,
      although poor outcomes are associated with pretreatment clinical status, it is
      difficult to predict posttreatment symptom severity with a high degree of
      accuracy across different research samples. 

PMID- 24680229
TI  - Teachers' self-efficacy, perceived effectiveness beliefs, and reported use of
      cognitive-behavioral approaches to bullying among pupils: effects of in-service
      training with the I DECIDE program.
AB  - Despite the promise of being effective in tacking bullying and conduct disorder,
      cognitive-behavioral (C-B) interventions are underused by teachers. Little
      detailed information exists as to why this is the case. The current study with
      junior school teachers in the U.K. (N=249) confirmed this low reported usage and
      showed that while teachers tended to believe that C-B approaches would be
      effective, most held rather low self-efficacy beliefs. Attending a workshop on a
      specific C-B approach, the I DECIDE program had positive effects on perceived
      effectiveness and self-efficacy beliefs, and longer durations of training (3days)
      were more beneficial than shorter durations (half/1day). In line with outcome
      expectancy theory and the theory of planned behavior, self-efficacy and duration
      of training predicted an increase in reported usage of I DECIDE across an 8-month
      period, and self-efficacy fully mediated the association between duration of
      training and increase in reported usage. The implications of these findings for
      overcoming impediments to the more widespread use of C-B approaches by teachers
      to tackling bullying were discussed, particularly the notion that attending
      training of sufficient duration coupled with a more explicit attention on
      fostering self-efficacy will pay dividends. 

PMID- 24680228
TI  - Modular cognitive-behavioral therapy for body dysmorphic disorder: a randomized
      controlled trial.
AB  - There are few effective treatments for body dysmorphic disorder (BDD) and a
      pressing need to develop such treatments. We examined the feasibility,
      acceptability, and efficacy of a manualized modular cognitive-behavioral therapy
      for BDD (CBT-BDD). CBT-BDD utilizes core elements relevant to all BDD patients
      (e.g., exposure, response prevention, perceptual retraining) and optional modules
      to address specific symptoms (e.g., surgery seeking). Thirty-six adults with BDD
      were randomized to 22 sessions of immediate individual CBT-BDD over 24 weeks
      (n=17) or to a 12-week waitlist (n=19). The Yale-Brown Obsessive-Compulsive Scale
      Modified for BDD (BDD-YBOCS), Brown Assessment of Beliefs Scale, and Beck
      Depression Inventory-II were completed pretreatment, monthly, posttreatment, and
      at 3- and 6-month follow-up. The Sheehan Disability Scale and Client Satisfaction
      Inventory (CSI) were also administered. Response to treatment was defined as
      >=30% reduction in BDD-YBOCS total from baseline. By week 12, 50% of participants
      receiving immediate CBT-BDD achieved response versus 12% of waitlisted
      participants (p=0.026). By posttreatment, 81% of all participants (immediate CBT
      BDD plus waitlisted patients subsequently treated with CBT-BDD) met responder
      criteria. While no significant group differences in BDD symptom reduction emerged
      by Week 12, by posttreatment CBT-BDD resulted in significant decreases in BDD
      YBOCS total over time (d=2.1, p<0.0001), with gains maintained during follow-up.
      Depression, insight, and disability also significantly improved. Patient
      satisfaction was high, with a mean CSI score of 87.3% (SD=12.8%) at
      posttreatment. CBT-BDD appears to be a feasible, acceptable, and efficacious
      treatment that warrants more rigorous investigation. 

PMID- 24680230
TI  - Enhancing the benefits of written emotional disclosure through response training.
AB  - Writing about a personal stressful event has been found to have psychological and
      physical health benefits, especially when physiological response increases during
      writing. Response training was developed to amplify appropriate physiological
      reactivity in imagery exposure. The present study examined whether response
      training enhances the benefits of written emotional disclosure. Participants were
      assigned to either a written emotional disclosure condition (n=113) or a neutral
      writing condition (n=133). Participants in each condition wrote for 20 minutes on
      3 occasions and received response training (n=79), stimulus training (n=84) or no
      training (n=83). Heart rate and skin conductance were recorded throughout a 10
      minute baseline, 20-minute writing, and a 10-minute recovery period. Self
      reported emotion was assessed in each session. One month after completing the
      sessions, participants completed follow-up assessments of psychological and
      physical health outcomes. Emotional disclosure elicited greater physiological
      reactivity and self-reported emotion than neutral writing. Response training
      amplified physiological reactivity to emotional disclosure. Greater heart rate
      during emotional disclosure was associated with the greatest reductions in event
      related distress, depression, and physical illness symptoms at follow-up,
      especially among response trained participants. Results support an exposure
      explanation of emotional disclosure effects and are the first to demonstrate that
      response training facilitates emotional processing and may be a beneficial
      adjunct to written emotional disclosure. 

PMID- 24680232
TI  - A pilot randomized controlled trial of the effects of cognitive-behavioral
      therapy for insomnia on sleep and daytime functioning in college students.
AB  - The purpose of this study was to pilot test if cognitive behavioral therapy for
      insomnia (CBT-I) is an effective intervention for insomnia and daytime
      functioning in college students. College students' developmental stage and
      lifestyle are significantly different than the general adult population, yet
      there have been no studies of CBT-I in this age group. Thirty-four college
      students (ages 18-27; M=19.71, SD=2.10) were randomly assigned to and completed
      either six sessions of CBT-I or a 6-week wait list control (WLC). All
      participants completed 1-week sleep diaries and actigraphy, as well as sleep and
      daytime functioning questionnaires at baseline and posttreatment. The treatment
      group repeated all measures at 3-month follow-up. Students who received CBT-I
      showed greater baseline to posttreatment improvements in sleep efficiency, sleep
      onset latency, number of awakenings, time awake after sleep onset, sleep quality,
      insomnia severity, dysfunctional beliefs about sleep, general fatigue, and global
      sleep quality than the WLC group. These improvements were durable at 3-month
      follow-up. Ninety-four percent of participants in the CBT-I condition completed
      at least 4 sessions of treatment. Significantly more participants in the CBT-I
      group than the WLC group responded (68.8% vs 7.7%, respectively) and remitted
      (68.8% vs 15.4%, respectively). CBT-I is an effective treatment for insomnia in
      college students. This study found that treatment responses were similar to
      results from studies in the general population. The treatment appeared to be well
      tolerated based on very low attrition rates. 

PMID- 24680231
TI  - Feasibility study of an interactive multimedia electronic problem solving
      treatment program for depression: a preliminary uncontrolled trial.
AB  - Computer-based depression interventions lacking live therapist support have
      difficulty engaging users. This study evaluated the usability, acceptability,
      credibility, therapeutic alliance and efficacy of a stand-alone multimedia,
      interactive, computer-based Problem Solving Treatment program (ePSTTM) for
      depression. The program simulated live treatment from an expert PST therapist,
      and delivered 6 ePSTTM sessions over 9weeks. Twenty-nine participants with
      moderate-severe symptoms received the intervention; 23 completed a minimally
      adequate dose of ePSTTM (at least 4 sessions). Program usability, acceptability,
      credibility, and therapeutic alliance were assessed at treatment midpoint and
      endpoint. Depressive symptoms and health-related functioning were assessed at
      baseline, treatment midpoint (4weeks), and study endpoint (10weeks). Depression
      outcomes and therapeutic alliance ratings were also compared to previously
      published research on live PST and computer-based depression therapy.
      Participants rated the program as highly usable, acceptable, and credible, and
      reported a therapeutic alliance with the program comparable to that observed in
      live therapy. Depressive symptoms improved significantly over time. These
      findings also provide preliminary evidence that ePSTTM may be effective as a
      depression treatment. Larger clinical trials with diverse samples are indicated. 

PMID- 24680233
TI  - A comprehensive examination of the model underlying acceptance and commitment
      therapy for chronic pain.
AB  - The therapeutic model underlying Acceptance and Commitment Therapy (ACT) is
      reasonably well-established as it applies to chronic pain. Several studies have
      examined measures of single ACT processes, or subsets of processes, and have
      almost uniformly indicated reliable relations with patient functioning. To date,
      however, no study has performed a comprehensive examination of the entire ACT
      model, including all of its component processes, as it relates to functioning.
      The present study performed this examination in 274 individuals with chronic pain
      presenting for an assessment appointment. Participants completed a battery of
      self-report questionnaires, assessing multiple aspects of the ACT model, as well
      as pain intensity, disability, and emotional distress. Initial exploratory factor
      analyses examined measures of the ACT model and measures of patient functioning
      separately with each analysis identifying three factors. Next, the fit of a model
      including ACT processes on the one hand and patient functioning on the other was
      examined using Structural Equation Modeling. Overall model fit was acceptable and
      indicated moderate correlations among the ACT processes themselves, as well as
      significant relations with pain intensity, emotional distress, and disability.
      These analyses build on the existing literature by providing, to our knowledge,
      the most comprehensive evaluation of the ACT theoretical model in chronic pain to
      date. 

PMID- 24680234
TI  - Mechanisms of change in brief couple therapy for depression.
AB  - The goal of the present study was to investigate potential mechanisms of
      previously documented treatment effects for a brief, 5-session, problem-focused
      couple therapy for depression in a sample of 35 depressed women and their
      nondepressed husbands. The primary treatment effects were reducing women's
      depressive symptoms and their husbands' psychological distress and depression
      specific burden. Secondarily, treatment resulted in increased relationship
      satisfaction for both partners. Given these significant treatment changes
      observed in 5 sessions, we sought to examine the mechanisms of change by testing
      the following three factors as potential mediators: (a) negative behaviors and
      attitudes toward depression, (b) support provision, and (c) empathic
      communication towards the depressed female partners. Women's depression and
      husbands' depression-specific burden were alleviated by positive changes in their
      illness-related attitudes and behaviors. Improvements in women's marital
      satisfaction were also mediated by positive change in their illness-related
      attitudes and behaviors, along with perceptions of increased positivity and
      support from their husbands. Findings highlight the importance of targeting
      specific treatment agents in a brief couple therapy for depression such as
      psychoeducation about depression and support-building to increase partners'
      understanding and acceptance of the illness, and teaching communication skills to
      reduce negative behaviors and criticism that are replaced by more empathic
      communication towards the depressed individual. 

PMID- 24680235
TI  - The interaction of extraversion and anxiety sensitivity on social anxiety:
      evidence of specificity relative to depression.
AB  - Neuroticism and extraversion have been linked to the etiologies and course of
      anxiety and mood disorders, such that neuroticism is broadly associated with
      numerous disorders and extraversion is most strongly associated with social
      anxiety and depression. While previous research has established the broad
      associations between temperament and emotional disorders, less is known about the
      specific, proximal factors that are associated with them, and very few studies
      have situated these risk factors into a larger etiological model that specifies
      how they may relate to one another. The current study examined the interaction of
      extraversion and anxiety sensitivity (AS) in predicting social anxiety symptoms
      in a large, diagnostically diverse clinical sample (N=826). Symptoms were
      assessed with self-report and dimensional interview measures, and regression
      analyses were performed examining the main effects and interaction of
      extraversion and AS (examining both total and lower-order components) on social
      anxiety. Results showed that at higher levels of AS, the inverse relationship
      between extraversion and social anxiety was stronger, and the social concerns
      component of AS is responsible for this effect. This interaction was also
      observed with regard to depression symptoms, but the interaction was not present
      after accounting for shared variance (i.e., comorbidity) between depression and
      social anxiety symptoms. Clinical and theoretical implications of the results are
      discussed. 

PMID- 24680236
TI  - Predictors of adherence to a brief behavioral insomnia intervention: daily
      process analysis.
AB  - Behavioral interventions for insomnia are effective in improving sleep, yet
      adherence is variable, and predictors of adherence have not been consistently
      replicated. The relationships between daily variations in state factors at the
      initiation of treatment and adherence have not been investigated. Using 2-week,
      self-report online logs, this study determined, among 53 college students with
      probable insomnia, the associations of pretreatment factors and daily factors
      during treatment on daily variations in adherence to one session of behavioral
      treatments for insomnia. These treatments included stimulus control therapy
      (SCT), sleep restriction therapy (SRT), and sleep hygiene (SH). Low self-efficacy
      was associated with poorer SCT and SH adherence. Participants with a "bed partner
      or pet" at least some of the time had better SCT adherence. Greater total sleep
      time and poorer sleep quality were associated with poor SCT and SRT adherence the
      following night. Greater sleep efficiency was related to greater next night SCT
      and SRT adherence. Alcohol consumption was related to poorer SRT and SH adherence
      the following night. Future studies should test the replicability of these
      findings. Adherence trials may want to test whether discouraging alcohol intake,
      enhancing treatment-related self-efficacy, and monitoring and providing feedback
      on sleep, early in treatment, affects adherence. 

PMID- 24680237
TI  - Lack of association between Press Ganey emergency department patient satisfaction
      scores and emergency department administration of analgesic medications.
AB  - STUDY OBJECTIVE: We explore the relationship between Press Ganey emergency
      department (ED) patient satisfaction scores and ED administration of analgesic
      medications, including amount of opioid analgesics received, among patients who
      completed a patient satisfaction survey. METHODS: We conducted a secondary data
      analysis of Press Ganey ED patient satisfaction surveys from patients discharged
      from 2 academic, urban EDs October 2009 to September 2011. We matched survey
      responses to data on opioid and nonopioid analgesics administered in the ED,
      demographic characteristics, and temporal factors from the ED electronic medical
      records. We used polytomous logistic regression to compare quartiles of overall
      Press Ganey ED patient satisfaction scores to administration of analgesic
      medications, opioid analgesics, and number of morphine equivalents received. We
      adjusted models for demographic and hospital characteristics and temporal
      factors. RESULTS: Of the 4,749 patients who returned surveys, 48.5% received
      analgesic medications, and 29.6% received opioid analgesics during their ED
      visit. Mean overall Press Ganey ED patient satisfaction scores for patients
      receiving either analgesic medications or opioid analgesics were lower than for
      those who did not receive these medications. In the univariable polytomous
      logistic regression analysis, receipt of analgesic medications, opioid
      analgesics, and a greater number of morphine equivalents were associated with
      lower overall scores. However, in the multivariable analysis, receipt of
      analgesic medications or opioid analgesics was not associated with overall
      scores, and receipt of greater morphine equivalents was inconsistently associated
      with lower overall scores. CONCLUSION: Overall Press Ganey ED patient
      satisfaction scores were not primarily based on in-ED receipt of analgesic
      medications or opioid analgesics; other factors appear to be more important.

PMID- 24680238
TI  - Efficacy of right axillary artery perfusion for antegrade cerebral perfusion in
      open total arch repair.
AB  - OBJECTIVE: Right axillary artery (RAxA) perfusion was introduced for selective
      antegrade cerebral perfusion in total aortic arch repair to prevent cerebral
      embolism derived from arterial cannulation. However, the strategic benefits and
      long-term results regarding the cannulation site remain controversial. We
      retrospectively compared the outcomes between propensity score-matched patients
      with and without using RAxA cannulation. METHODS: Between 2006 and 2012, 260
      consecutive patients underwent total arch repair with antegrade cerebral
      perfusion and moderate hypothermia at a single institution. RAxA cannulation was
      added in 142 patients (54.6%), and 70 propensity score-matched pairs were
      obtained. RESULTS: There were no significant differences in 30-day (2.9% [2 of
      70] vs 5.7% [4 of 70]; P = .415 and in-hospital death (5.7% [4 of 70] vs 5.7% [4
      of 70]; P = 1.000) between matched pairs. Although there was no significant
      difference in the occurrence of postoperative stroke (8.6% [6 of 70] vs 8.6% [6
      of 70]; P = 1.000), the new rate of new occurrence of postoperative paraparesis
      was lower in patients with RAxA perfusion (0% [0 of 70] vs 4.3% [3 of 70]; P =
      .067). With a mean follow-up period of 1057 +/- 686 days, the overall 5-year
      survival was 90.6% and was 89.6% for patients with RAxA perfusion. Thee
      difference in survival between patients with and without RAxA perfusion was not
      significant. CONCLUSIONS: RAxA perfusion is a useful option for total aortic arch
      repair, and the midterm outcomes were satisfactory. However, RAxA perfusion did
      not completely prevent stroke in patients with an atherothrombotic aorta.

PMID- 24680239
TI  - Recanalization of the intentionally interrupted inferior vena cava.
AB  - Intentional interruption of the inferior vena cava with caval ligation and a
      Mobin-Uddin filter was once commonly used to prevent recurrent pulmonary emboli
      and was associated with significant mortality and morbidity, including a high
      incidence of post-thrombotic syndrome. Recanalization of an intentionally
      interrupted inferior vena cava has been rarely described in literature and is
      commonly considered futile. We describe two patients with post-thrombotic
      syndrome as a late complication of caval ligation and a thrombosed Mobin-Uddin
      filter, with significant and sustained improvement after endovascular
      recanalization. 

PMID- 24680240
TI  - Correlation of pre-existing radial artery macrocalcifications with late patency
      of primary radiocephalic fistulas in diabetic hemodialysis patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of pre-existing
      radial artery macrocalcification (Monckeberg type of arteriosclerosis) on patency
      rates of radiocephalic fistulas (RCFs) in diabetic end-stage renal disease (ESRD)
      patients undergoing hemodialysis. METHODS: In this observational prospective
      study, the long-term patency rates (primary outcome measures) of RCFs in ESRD
      diabetics who had Monckeberg radial (+/-brachial) artery disease (calcified [C]
      group) were compared with those obtained in ESRD diabetics who had healthy,
      noncalcified vessels before RCF construction (healthy [H] group). Vessel
      calcification was assessed by plain two-dimensional radiography. For inclusion in
      the C-group, uniform linear railroad track-type macrocalcifications of at least 6
      cm in length, in the medial wall of the radial artery ipsilateral to RCF
      creation, were required. Patients were included in the H-group if the radial
      artery ipsilateral to the RCF creation was free of any macrocalcification, of
      either intima or media type. Any intimal-like plaque with irregular and patchy
      distribution was an exclusion criterion for both groups. Patients in both groups
      also were required to have suitable upper limb vascular anatomy on the basis of
      ultrasound imaging before RCF creation (cephalic vein of minimum diameter of 1.6
      mm, without stenosis or thrombosis in all outflow areas, and radial artery of
      minimum diameter of 1.5 mm, without proximal hemodynamically significant
      stenosis). Secondary outcome measures included all-cause mortality. Kaplan-Meier
      statistics were used for comparison between groups. RESULTS: The arm radiograph
      at the site of possible fistula construction showed abnormality in 39 patients (C
      group, 47 RCFs), whereas 33 patients had noncalcified ("healthy") vascular
      anatomy (H-group, 40 RCFs). Mean duration of the diabetic disease at the time of
      RCF creation was 8.9 +/- 5.6 years (range, 2-25 years) for the H-group and 14 +/-
      9.9 years (range, 1-40 years) for the C-group (P = .018). The mean follow-up
      period for H-group and C-group was 51.9 +/- 35.9 months (range, 0.1-126 months)
      and 26.1 +/- 31.6 months (range, 0.1-144 months), respectively (P = .0006). Forty
      four patients died during the follow-up period. Primary patency rates at 12, 24,
      36, and 48 months for C-group vs H-group were 50.2% vs 80%, 36.5% vs 72.3%, 32.4%
      vs 67.9%, and 29.1% vs 59.3% (P = .0019). Respective values for secondary patency
      rates were 52.4% vs 87.5%, 40.9% vs 82.4%, 36.6% vs 78.1%, and 33.2% vs 72.8% (P
      = .00064). Patient survival rates at 24 and 48 months were 56.1% and 46.4% for C
      group and 92.4% and 67.4% for H-group, respectively (P = .05). CONCLUSIONS: ESRD
      diabetics with radial artery Monckeberg calcifications receiving RCFs had worse
      late clinical outcomes compared with ESRD diabetics with healthy distal arm
      vessels receiving the same access. The long-term benefit of RCFs may be lost in
      diabetics with extensively calcified vessels, and preferably the brachial artery
      should be used instead.

PMID- 24680241
TI  - Postapproval outcomes of juxtarenal aortic aneurysms treated with the Zenith
      fenestrated endovascular graft.
AB  - OBJECTIVE: The objective of this study was to evaluate postapproval outcomes of
      patients with juxtarenal aortic aneurysms treated with the Zenith fenestrated
      endovascular graft (Cook Inc, Bloomington, Ind). METHODS: We reviewed clinical
      data of consecutive patients treated with the Zenith fenestrated endovascular
      graft in the United States at seven institutions with early commercial access
      from July 2012 to December 2012. Clinical outcomes and compliance to anatomic
      guidelines were compared with results of the U.S. fenestrated trial (USFT).
      RESULTS: Fifty-seven patients were treated. There were significantly more (P <
      .05) patients with coronary artery disease, myocardial infarction, and
      preoperative renal insufficiency than in the USFT. Thirty-six patients (63.2%)
      did not meet the USFT anatomic criteria of a >4-mm infrarenal neck, and there
      were significantly more mesenteric stents (13 vs 0; P < .05) used in this group
      than in the USFT, reflecting the higher anatomic complexity of these patients.
      The total operative time was 250.2 +/- 14.8 minutes, the fluoroscopy time was
      68.9 +/- 4.47 minutes, and the average volume of contrast material was 108.6 +/-
      5.6 mL. Technical success was 100% in regard to aneurysm exclusion, although the
      left renal fenestration was not able to be aligned in two patients, and one
      patient had a kinked renal stent that was successfully restented. During this
      time period, there were a total of 10 endoleaks, of which two were type III and
      eight were type II. CONCLUSIONS: Despite higher rates of comorbidities and more
      challenging anatomy, early 30-day outcomes of juxtarenal aortic aneurysms treated
      postapproval with the Zenith fenestrated endovascular graft compare well with
      USFT data. Future studies are needed to assess durability of this treatment
      modality as the technology diffuses and data mature.

PMID- 24680242
TI  - Endovascular treatment for symptomatic stent failures in long-segment chronic
      total occlusion of femoropopliteal arteries.
AB  - OBJECTIVE: The objective of this study was to evaluate the outcomes of the
      secondary endovascular treatment (SEVT) for symptomatic recurrences in long
      segment chronic total occlusion (CTO) of femoropopliteal arteries (FPAs) and to
      investigate the factors affecting the outcomes. METHODS: Data of patients
      undergoing FPA stent implantation for primary, long-segment (>10 cm) CTO lesions
      and receiving endovascular intervention for symptomatic recurrences more than
      once in our institution from July 1, 2008, to September 1, 2012, were reviewed.
      Follow-up results referring to SEVT procedures were analyzed, including primary
      patency, limb salvage (LS) rate, technical success rate, and prevalence of
      procedure-related complications. Primary patency and LS were analyzed with Kaplan
      Meier curves. Univariate and multivariable analyses were performed to identify
      factors associated with recurrent restenosis with a Cox proportional hazards
      model. RESULTS: Ninety-one patients (mean age, 75.1 years) were included. The
      indications for SEVT were claudication (38.5%) and critical limb ischemia
      (61.5%). Preprocedural ankle-brachial index was 0.37 +/- 0.16. The median time
      between initial endovascular treatment and SEVT was 6.5 months (range, 1.0-24.4
      months). The arteries in 63 limbs were totally occluded. Fractures were found in
      30 (18.8%) of the initially placed stents. Successful recanalization was achieved
      in 82 limbs (90.1%). The mean postprocedural ankle-brachial index was 0.84 +/-
      0.15 in those limbs that were successfully recanalized. The complication rate was
      9.9%. One patient died of cerebral hemorrhage during catheter-directed
      thrombolysis. Other complications included the development of a groin hematoma (n
      = 5), distal embolization (n = 1), formation of a femoral pseudoaneurysm (n = 1),
      and development of acute heart failure (n = 1). The mean follow-up period was
      11.0 +/- 5.6 months. The cumulative primary patency rate after SEVT was 66.9% and
      52.0% at 12 and 24 months. The LS rate since SEVT was 91.2% and 81.1% at 12 and
      24 months. The multivariate analysis showed that stent fracture and stent overlap
      were independent predictors of recurrent restenosis (hazard ratio, 3.07; 95%
      confidence interval, 1.40-6.74; P = .005; hazard ratio, 4.75; 95% confidence
      interval, 1.77-12.75; P = .002). CONCLUSIONS: Endovascular treatment is feasible
      for FPA stent failure in long-segment CTO. However, SEVT does not achieve durable
      patency. Stent fracture and overlap are related to recurrent restenosis.

PMID- 24680243
TI  - Wave propagation in layered piezoelectric rectangular bar: an extended orthogonal
      polynomial approach.
AB  - Wave propagation in multilayered piezoelectric structures has received much
      attention in past forty years. But the research objects of previous research
      works are only for semi-infinite structures and one-dimensional structures, i.e.,
      structures with a finite dimension in only one direction, such as horizontally
      infinite flat plates and axially infinite hollow cylinders. This paper proposes
      an extension of the orthogonal polynomial series approach to solve the wave
      propagation problem in a two-dimensional (2-D) piezoelectric structure, namely, a
      multilayered piezoelectric bar with a rectangular cross-section. Through
      numerical comparison with the available reference results for a purely elastic
      multilayered rectangular bar, the validity of the extended polynomial series
      approach is illustrated. The dispersion curves and electric potential
      distributions of various multilayered piezoelectric rectangular bars are
      calculated to reveal their wave propagation characteristics. 

PMID- 24680244
TI  - Differential impacts of achieved heart rate and achieved dose of beta-blocker on
      clinical outcomes in heart failure with and without atrial fibrillation.

PMID- 24680245
TI  - Cardiovascular evaluation in Turner Syndrome: the evidence, the reality and the
      challenges.

PMID- 24680246
TI  - Two-year outcomes after first- or second-generation drug-eluting stent
      implantation in patients with in-stent restenosis. A PRODIGY trial substudy.

PMID- 24680247
TI  - Letter regarding Li et al. "prognostic impact of late gadolinium enhancement by
      cardiac magnetic resonance imaging in patients with non-ischaemic dilated
      cardiomyopathy".

PMID- 24680248
TI  - Conversion from persistent to paroxysmal atrial fibrillation after pulmonary vein
      isolation is a good sign.

PMID- 24680249
TI  - Risk markers for coronary plaque progression and destabilization beyond LDL
      cholesterol in acute coronary syndrome.

PMID- 24680251
TI  - Transcatheter intervention following ambrisentan treatment in an adult patient
      with patent ductus arteriosus and severe pulmonary hypertension.

PMID- 24680250
TI  - Bivalirudin in percutaneous coronary intervention: the EUROpean BiValIrudin
      UtiliSatION in Practice (EUROVISION) Registry.
AB  - PURPOSE: The prospective EUROVISION Registry was designed to capture patterns of
      use and short term outcomes in consecutive patients undergoing PCI with
      bivalirudin (BIV) in European centres. METHODS: A total of 2018 consecutive BIV
      treated patients were included from 58 sites in 5 countries (Germany, Italy,
      France, Austria, United Kingdom). In-hospital and 30-day outcomes were
      prospectively collected and included: death, myocardial infarction (MI), stroke,
      urgent revascularization (URV), major and minor bleeding, stent thrombosis (ST)
      and thrombocytopenia (TCP). RESULTS: In this all-comer population, indication for
      PCI included STEMI (34%), NSTEMI (25%), unstable angina (16%) and stable angina
      (26%). Diabetes was present in 24% of patients and 30% of cases were performed
      via radial access. Preloading with a P2Y12 inhibitor was frequent (74%) while
      procedural glycoprotein inhibitor (GPI) use was low at 4.2%. Almost half (45%) of
      patients had received at least one additional anticoagulant prior to receiving
      BIV for PCI. The overall 30-day mortality was 1.0%, with low rates of MI (1.1%),
      URV (0.8%), ST (0.3%) and stroke (0.2%). The rate of ACUITY major bleeding was
      1.6% and no TCP was reported. Dosing variations representing possible under- or
      over-dosing of BIV were frequent at 35%. CONCLUSION: In this prospective registry
      of consecutive patients intended for PCI, use of BIV was associated with low
      rates of ischemic complications and excellent safety.

PMID- 24680252
TI  - First description of arrhythmogenic right ventricular cardiomyopathy in a patient
      with Down syndrome.

PMID- 24680253
TI  - Insufficient use of mineralocorticoid receptor antagonists in patients that
      underwent renal sympathetic denervation for resistant hypertension.

PMID- 24680254
TI  - The complex fractionated atrial electrogram may be the sine qua non of atrial
      fibrillation, but qualitatively or quantitatively?

PMID- 24680255
TI  - The prevalence of antiretroviral multidrug resistance in highly active
      antiretroviral therapy-treated patients with HIV/AIDS between 2004 and 2009 in
      South Korea.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) including protease
      inhibitors (PIs) has been used in South Korea since 1997. Currently, more than 20
      types of antiretroviral drugs are used in the treatment of human immunodeficiency
      virus-infected/acquired immune deficiency syndrome patients in South Korea.
      Despite the rapid development of various antiretroviral drugs, many drug
      resistant variants have been reported after initiating HAART, and the efficiency
      of HAART is limited by these variants. OBJECTIVES: To investigate and estimate
      the annual antiretroviral drug resistance and prevalence of antiretroviral multi
      class drug resistance in Korean patients with experience of treatment. STUDY
      DESIGN: The amplified HIV-1 pol gene in 535 patients requested for genotypic drug
      resistance testing from 2004 to 2009 by the Korea Centers for Disease Control and
      Prevention was sequenced and analyzed annually and totally. The prevalence of
      antiretroviral drug resistance was estimated based on "SIR" interpretation of the
      Stanford sequence database. RESULTS: Of viruses derived from 787 specimens, 380
      samples (48.3%) showed at least one drug class-related resistance. Predicted NRTI
      drug resistance was highest at 41.9%. NNRTI showed 27.2% resistance with 23.3%
      for PI. The percent of annual drug resistance showed similar pattern and slightly
      declined except 2004 and 2005. The prevalence of multi-class drug resistance
      against each drug class was: NRTI/NNRTI/PI, 9.8%; NRTI/PI, 21.9%; NNRTI/PI,
      10.4%; and NRTI/NNRTI, 21.5%. CONCLUSIONS: About 50% and less than 10% of
      patients infected with HIV-1 have multidrug and multiclass resistance linked to
      16 antiretroviral drugs, respectively. The significance of this study lies in its
      larger-scale examination of the prevalence of drug-resistant variants and
      multidrug resistance in HAART-experienced patients in South Korea.

PMID- 24680257
TI  - [Health services should be promoted to improve cardiovascular prevention and
      rehabilitation in China].

PMID- 24680256
TI  - Binge drinking in alcohol-preferring sP rats at the end of the nocturnal period.
AB  - Sardinian alcohol-preferring (sP) rats have been selectively bred for high
      alcohol preference and consumption using the standard 2-bottle "alcohol (10%,
      v/v) vs. water" choice regimen with unlimited access; under this regimen, sP rats
      daily consume 6-7 g/kg alcohol. The present study assessed a new paradigm of
      alcohol intake in which sP rats were exposed to the 4-bottle "alcohol (10%, 20%,
      and 30%, v/v) vs. water" choice regimen during one of the 12 h of the dark phase
      of the daily light/dark cycle; the time of alcohol exposure was changed daily in
      a semi-random order and was unpredictable to rats. Alcohol intake was highly
      positively correlated with the time of the drinking session and averaged
      approximately 2 g/kg when the drinking session occurred during the 12th hour of
      the dark phase. Alcohol drinking during the 12th hour of the dark phase resulted
      in (a) blood alcohol levels averaging approximately 100 mg% and (b) severe signs
      of alcohol intoxication (e.g., impaired performance at a Rota-Rod task). The
      results of a series of additional experiments indicate that (a) both singular
      aspects of this paradigm (i.e., unpredictability of alcohol exposure and
      concurrent availability of multiple alcohol concentrations) contributed to this
      high alcohol intake, (b) alcohol intake followed a circadian rhythm, as it
      decreased progressively over the first 3 h of the light phase and then maintained
      constant levels until the beginning of the dark phase, and (c) sensitivity to
      time schedule was specific to alcohol, as it did not generalize to a highly
      palatable chocolate-flavored beverage. These results demonstrate that
      unpredictable, limited access to multiple alcohol concentrations may result in
      exceptionally high intakes of alcohol in sP rats, modeling - to some extent -
      human binge drinking. A progressively increasing emotional "distress" associated
      to rats' expectation of alcohol might be the neurobehavioral basis of this
      drinking behavior. 

PMID- 24680258
TI  - [Rethinking, comment and query of the 2013 ACC/AHA guideline on the treatment of
      blood cholesterol to reduce atherosclerotic cardiovascular risk in adults].

PMID- 24680259
TI  - [Chinese expert consensus of psychological prescription for patients in
      cardiovascular department].

PMID- 24680260
TI  - [Annex 1 Generalized anxiety disorder 7].

PMID- 24680262
TI  - [Annex 3 Hospital anxiety and depression scale].

PMID- 24680261
TI  - [Annex 2 Patient health questionnaire depression scale].

PMID- 24680263
TI  - [Predictors of in-stent restenosis in coronary heart disease patients
      complicating with diabetes mellitus within 2 years after drug-eluting stents
      implantation].
AB  - OBJECTIVE: To determine predictors for in-stent restenosis (ISR) within 2 years
      after drug-eluting stent (DES) implantation in coronary heart disease patients
      complicating with diabetes mellitus and to establish predictive model. METHODS:
      We retrospectively analyzed clinical data of patients underwent DES implantation
      in our hospital between January 2005 and December 2012. Using random number
      generated by SPSS 17.0, a total of 3 073 cases were randomly divided into two
      cohort, model derivation cohort (MDC) and model validation cohort (MVC). MDC (2
      048 cases) was divided into in-stent restenosis (ISR) group and control group.
      Predictors were identified using univariable and multivariable logistic
      regression analysis in MDC. Integer point values were assigned to each predictor
      based upon their beta coefficient in multivariable logistic regression model to
      establish scoring model. The summed scores of each case in MVC (1 025 cases) were
      calculated to test predictive ability of the model. RESULTS: Of all these 3 073
      cases, 217 cases (7.1%) were diagnosed with ISR within 2 year after DES
      implantation. The incidence of ISR within 2 year after DES implantation was 7.3%
      (149 cases) in MDC and logistic regression analysis identified six ISR risk
      factors: multiple target vessels (OR = 3.69, 95%CI: 2.65-8.93, P = 0.000),
      diffused lesions (OR = 2.92, 95%CI: 2.03-6.46, P = 0.000), GFR < 60 ml*min(
      1).1.73 m(-2) (OR = 4.73, 95%CI: 3.51-10.62, P = 0.000), smoking (OR = 3.37,
      95%CI: 2.39-8.46, P = 0.000), age < 60 years old (OR = 1.44, 95%CI:1.26-4.63, P =
      0.024), HbAlc >= 6.3% (OR = 2.48, 95%CI: 1.84-4.27, P = 0.002). Risk score was
      well associated with the rate of ISR in MVC. Sensitivity was 76.5% (95%CI: 64.6%
      85.9%), specificity was 76.1% (95%CI: 73.2%-78.7%), and areas under the ROC curve
      was 0.851(95%CI:0.813-0.890, P = 0.000) when score was set at 5.5. CONCLUSIONS:
      The incidence of ISR in coronary heart disease patients complicating with
      diabetes mellitus within 2 years after DES implantation is relatively low.
      Several factors are associated with ISR in these patients and risk for ISR could
      be reliably identified by the established scoring model.

PMID- 24680264
TI  - [Impact of simultaneous renal artery and coronary artery stenting on cardiac and
      renal function in patients with renal artery stenosis and coronary artery
      disease].
AB  - OBJECTIVE: To investigate the impact of simultaneous percutaneous transluminal
      renal artery stenting (PTRAS) and percutaneous coronary artery interventions
      (PCI) on cardiac and renal function in patients with renal artery stenosis (RAS)
      and coronary artery disease (CAD), and explore the factors affecting the long
      term prognosis. METHODS: This retrospective cohort study enrolled 169 patients
      with RAS and CAD from January 2006 to January 2010, 149 patients were intervened
      with PTRAS and PCI simultaneously (combined group) and the remaining 20 patients
      were treated with PCI (PCI group). All patients were followed up for at least 2
      years. Clinical data including blood pressure, estimated glomerular filtration
      rate (eGFR), echocardiography and major adverse events were obtained. RESULTS:
      The average stenotic ratio of the left and right renal artery in PCI group were
      significantly lower than those in combined group (both P < 0.01). After 2 years,
      there was a significant decrease in systolic blood pressure compared to baseline
      level in the combined group (P < 0.01). In the PCI group, both systolic blood
      pressure and diastolic blood pressure were significantly lower during follow-up
      than at the baseline level (both P < 0.01) . Echocardiography examination showed
      that left ventricular mass index (LVMI) during follow up was significantly lower
      than the baseline value in both groups, and the reduction extent in the combined
      group was larger than in PCI group (-55.6 g/m(2) vs.-12.8 g/m(2), P < 0.01) . In
      the combined group, the eGFR value decreased from (44.7 +/- 17.4) ml*min(-1)*1.73
      m(-2) to (41.7 +/- 18.9) ml*min(-1)*1.73 m(-2) (P < 0.01). eGFR level remained
      unchanged in PCI group (P > 0.05). Multivariate Cox regression analysis
      demonstrated that baseline renal dysfunction was not significantly related to the
      long-term adverse prognosis in combined group (HR = 0.986, P > 0.05).
      CONCLUSIONS: Simultaneous PTRAS and PCI are safe and effective for treating
      patients with RAS and CAD. Simultaneous PTRAS and PCI are beneficial on
      controlling blood pressure and reducing left ventricular mass index but has no
      impact on renal function change.

PMID- 24680265
TI  - [Effect of intracoronary tirofiban combined with nitroprusside injection through
      thrombus aspiration catheter during primary percutaneous coronary intervention on
      acute anterior myocardial infarction patients with heavy thrombosis burden].
AB  - OBJECTIVE: To explore the impact of intracoronary bolus administration of
      tirofiban combined with nitroprusside through thrombus aspiration catheter or
      thrombus aspiration alone on myocardial reperfusion and major adverse
      cardiovascular events rate in acute anterior myocardial infarction patients with
      heavy thrombosis burden. METHODS: Ninety consecutive acute anterior myocardial
      infarction patients with heavy thrombosis burden [(59.8 +/- 11.5) years old] were
      randomly assigned to thrombus aspiration group (Group A, n = 30), thrombus
      aspiration and intracoronary tirofiban bolus (25 ug/kg prior to the first balloon
      inflation,Group B, n = 30), thrombus aspiration and intracoronary tirofiban
      combined with nitroprusside bolus (200 ug prior to the first balloon inflation,
      Group C, n = 30) with random number table. Baseline clinical data, angiographic
      features before and after percutaneous coronary intervention (PCI) and major
      adverse cardiovascular events after PCI between 3 groups were compared. RESULTS:
      The baseline clinical data and angiographic features among 3 groups were similar
      (all P > 0.05) . The time of pain to balloon was (5.5 +/- 3.8) hours. After
      primary PCI, myocardial tissue perfusion was significantly better in Group C than
      in Group A and Group B: TMP grade < 3 [10.0% (3/30) vs. 40.0% (12/30) and 33.3%
      (10/30), P < 0.01 and P < 0.05]. Left ventricular ejection fraction at 5 to 7
      days after PCI also tended higher in Group C than in the other 2 groups (P =
      0.05). One patient died of heart failure at 7th day after PCI in Group A, and no
      patient died in Group B and C. Thirty days after PCI, there was no re-myocardial
      infarction and target vessel revascularization event among 3 groups. The bleeding
      complication rate during 30 days follow-up was similar among 3 groups (P > 0.05)
      . CONCLUSION: Intracoronary bolus application of tirofiban combined with
      nitroprusside through thrombus aspiration catheter after thrombus aspiration is
      associated with an improvement of myocardial reperfusion without increasing
      bleeding complication and other adverse cardiovascular events rate compared with
      thrombus aspiration alone in patients with acute anterior myocardial infarction
      and heavy thrombosis burden undergoing primary PCI.

PMID- 24680266
TI  - [An experiment study of transcatheter transapical aortic valve implantation with
      a new domestic balloon-expandable bioprosthetic aortic valve in goats].
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of transcatheter
      transapical implantation of a new domestic balloon-expandable bioprosthetic
      aortic valve in goats. METHODS: We developed a new tube-like balloon-expandable
      bioprosthetic aortic valve which was made from cobalt-chromium alloy and bovine
      pericardium. Briefly, fresh bovine pericardium was trimmed into artificial
      leaflets and sutured into the cobalt-chromium alloy stent by hand post cell
      extracting and anti-calcification treatments. A left anterolateral mini
      thoracotomy was performed in the 5(th) intercostal space of 5 goats. After
      opening the pericardium, the apex of the left ventricle was punctured, a stiff
      guidewire was positioned across the aortic arch and anchored in the descending
      aorta. The delivery catheter (22 F) was then introduced through the stiff
      guidewire into the aorta arch under fluoroscopic guidance. After correct valve
      position was confirmed by digital subtraction angiography, the valved stent was
      implanted after rapid inflation of the balloon. The immediate results of
      implanted valved stents were evaluated with angiography and echocardiography.
      RESULTS: Four devices were successfully implanted into aortic valve position of
      goats and one goat died of severe aortic valve regurgitation because the valved
      stent was implanted below the normal position.Immediate observation after
      procedure in 4 goats by angiography and echocardiography showed that the valved
      stents were in the desired position after implantation. Mild paravalvular leakage
      were found in 3 out of the 4 survived goats and there were no moderate to severe
      aortic regurgitation in survived goats. CONCLUSION: The procedure of
      transcatheter transapic aortic valve implantation with our new-type domestic
      balloon-expandable valved stent and delivery system is feasible and effective.

PMID- 24680267
TI  - [The efficacy of permanent epicardial pacing in the treatment of pacing-dependent
      patients with cardiac device related endocarditis].
AB  - OBJECTIVE: Permanent epicardial pacemaker is seldom used clinically and it is
      even less likely to be used for the treatment of seriously ill pacing-dependent
      patients with cardiac electronic device related endocarditis. METHOD: We
      retrospectively analyzed the feasibility and efficacy of permanent epicardial
      pacing for the treatment of 3 pacing-dependent patients with cardiac electronic
      device related endocarditis, who were treated by removal of all pacemaker devices
      and reimplantation of permanent epicardial pacing system combined with
      antibiotics. The reason of using epicardial pacing system was as follows:
      uncontrolled sepsis (case 1); big vegetation on the electrode of pacemaker and
      tricuspid valve but not a candidate for open heart surgery because of high
      operative risk (case 2); occlusion of superior vena cava (case 3). RESULTS: All 3
      patients were cured with the treatment of extraction of infected pacing system,
      re-implanted permanent epicardial pacing system and antibiotics. The permanent
      epicardial pacemaker worked well during the 2-12 months follow-up period and
      there was no recurrence of infection. CONCLUSIONS: Permanent epicardial pacing is
      useful and efficient in treatment of seriously ill and high risk pacing-dependent
      patients with cardiac device related endocarditis.

PMID- 24680268
TI  - [Clinical characteristics of 9 patients with pulmonary artery sarcoma].
AB  - OBJECTIVE: To investigate the clinical characteristics of pulmonary artery
      sarcoma (PAS) and to improve doctors' awareness and the early diagnosis of this
      disease. METHODS: The clinical data of 9 cases confirmed by operation and
      pathology of PAS from November 2001 to November 2012 in Beijing Anzhen Hospital
      were reviewed. The clinical characteristics, laboratory tests, imaging
      manifestation, pathology as well as follow-up were studied. Survival was
      determined by the Kaplan-Merier method. RESULTS: (1)Main clinical manifestations
      were chest distress (8/9), palpitation (2/9), syncope (2/9), cough (2/9), weight
      loss (2/9) and chest pain (1/9). (2)Lactate dehydrogenase (LDH) , high
      sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR)
      were all elevated to different extents, but D-Dimer remained in the normal range.
      (3) Seven cases received CTPA examination and evidenced filling defect in the
      main pulmonary artery trunk (6/7), left pulmonary artery (6/7), right pulmonary
      artery (7/7). 7 cases received TTE examination and showed enlarged right
      ventricle (6/7) : mean right ventricular end-diastolic diameter was (38.54 +/-
      16.30) mm; enlarged right atrium (7/7): mean right atrium diameter was (55.11 +/-
      5.45) mm; and tricuspid insufficiency (7/7) : estimated mean pulmonary artery
      pressure was (81.14 +/- 21.17) mmHg (1 mmHg = 0.133 kPa) , and pulmonary stenosis
      (5/7) . Four cases received deep venous ultrasound examination and deep venous
      thrombosis (DVT) was found in 1 patient. Four cases received Ganz catheter
      examination and the preoperative and postoperative mean pulmonary artery pressure
      was (52.00 +/- 5.23) mmHg and (23.00 +/- 5.60) mmHg, respectively. (4) All 9
      patients received surgery and intimal sarcoma was diagnosed in all of them.
      Leiomyosarcoma was diagnosed in 3 cases, leiomyo-angiosarcoma was diagnosed in 1
      case, undifferentiated sarcomas was diagnosed in 1 case. (5)The 1-, 3- and 5
      month survival was 71.4%, 53.6% and 35.7%, respectively, median survival time was
      5 months post surgery. CONCLUSION: PAS is difficult to differentiate with PTE.
      PAS should be suspected in patient with right atrium, right ventricular
      enlargement and early appeared right heart failure, and normal D-Dimer level.
      Outcome for PAS patients is poor despite surgery in this cohort.

PMID- 24680269
TI  - [Simvastatin attenuates oxidized low density lipoprotein induced oxidative stress
      in human umbilical vein endothelial cells via downregulating NADPH oxidase
      activity].
AB  - OBJECTIVE: To investigate the effects and related mechanism of simvastatin on
      oxidized low density lipoprotein(ox-LDL) induced oxidative stress in human
      umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were cultured in 6
      different culture media: control, ox-LDL, ox-LDL+vehicle, ox-LDL+0.1 umol/L
      simvastatin, ox-LDL+0.5 umol/L simvastatin, ox-LDL+1.0 umol/L simvastatin. HUVECs
      were incubated with ox-LDL (120 ug/ml) for 24 h in the presence or absence of
      different concentrations of simvastatin (0.1,0.5, 1.0 umol/L) . The fluorescence
      intensity for reactive oxygen species (ROS) in HUVECs was measured by a laser
      confocal scanning microscopy and a microplate reader.NADPH oxidase activity was
      measured by lucigenin chemiluminescence. p22(phox), gp91(phox), p47(phox) and
      p67(phox) mRNA expression of HUVECs post various treatments was detected by RT
      PCR. p22(phox) immunoprecipitates were immunoblotted for p47(phox) and total
      p22(phox) levels to identify p47(phox)/p22(phox) interaction. RESULTS:
      Simvastatin attenuated ox-LDL induced ROS generation and NADPH oxidase activity
      in a concentration dependent manner (all P < 0.05). In addition, simvastatin
      significantly downregulated mRNA expression of p22(phox), gp91(phox), p47(phox)
      and p67(phox) (all P < 0.05), as well as the interaction of p47(phox)/p22(phox)
      (P < 0.01). CONCLUSIONS: Simvastatin is an important regulator on NADPH subunits
      mRNA expressions and p47(phox)/p22(phox) interaction. Simvastatin attenuates ox
      LDL-induced oxidative stress in HUVECs via reducing NADPH oxidase activity.

PMID- 24680270
TI  - [Effect of catheter-based renal sympathetic denervation in pigs with rapid pacing
      induced heart failure].
AB  - OBJECTIVE: This study investigated the effect of catheter-based renal sympathetic
      denervation (RDN) in pigs with rapid pacing induced heart failure. METHODS: Heart
      failure was induced by rapid right ventricular pacing in 12 pigs and pigs were
      randomly divided into RDN group (n = 6): pacing+RDN at 7 days post pacing;
      control group (n = 6): pacing only. Echocardiography examination (LVEF, LVEDD and
      LVESD) was performed before pacing and at 1 and 2 weeks post pacing. Serum
      biochemical markers including renin, aldosterone and creatinine were also
      measured at baseline, 1 and 2 weeks after pacing. Repeated renal artery
      angiography was performed at 1 week after RDN. All pigs were sacrificed to
      examine the heart and renal pathology and renal artery sympathetic nerve staining
      at 2 weeks post pacing. RESULTS: LVEF decreased 1 week after rapid pacing from
      (60.5 +/- 6.0)% to (35.3 +/- 9.8)%. LVEF was significantly higher [(42.8 +/- 5.9)
      % vs. (33.4 +/- 9.7)%, P = 0.001 8] while LVESD was significantly lower [(28.4 +/
      3.7) mm vs. (33.0 +/- 2.0) mm, P = 0.001 6] in the RDN group than in the control
      group at 2 weeks post pacing. At 2 weeks after pacing, plasma concentrations of
      renin and aldosterone were significantly lower in RDN group compared to the
      control group (all P < 0.05) . Kidney function and blood pressure were comparable
      between the two groups at 2 weeks post pacing. There were no signs of renal
      damages such as renal artery stenosis, dissection and thrombus in all pigs after
      2 weeks pacing. Sympathetic neurons of adventitia were injured in RND group.
      CONCLUSION: RDN could significantly improve cardiac function and attenuate left
      ventricular remodeling via inhibiting renin-angiotensin-aldosterone system in
      this pacing induced pig heart failure model.

PMID- 24680271
TI  - [An improved protocol for primary culture of cardiomyocyte from neonatal rat].
AB  - OBJECTIVE: The present study describes an improved in vitro culture method for
      obtaining high purity, vital and fully functional cardiomyocytes from neonatal
      rat. METHODS: After cutting ventricular tissue with improved method, ventricular
      tissues were digested with low concentrations of trypsin overnight at 4  degrees
      C, and then underwent collagenase II digestion. Thereafter, cardiomyocytes were
      purified by combined differential adhesion and chemical inhibition methods.
      RESULTS: Adherent cardiomyocytes were seen at 12 h after culture, spontaneously
      beating cardiomyocytes were observed at 24 h after culture, crosslinked
      cardiomyocytes were found at 48 h after culture, adhesion clustered
      cardiomyocytes were seen at 72 h after culture, dense network formed from inter
      connected was evidenced together with radial arranged cell clusters and cell
      pseudopodia 96 h the mutual contact woven into and formed radically ordering cell
      clusters and island-like beating cardiomyocytes at 96 h after culture. The cell
      survival rate and purity were more than 98%. CONCLUSION: Fully functional
      spontaneous beating cardiomyocytes can be obtained by the use of this improved
      primary neonatal rat cardiomyocytes culture method.

PMID- 24680272
TI  - [A meta-analysis on the association between high-density lipoprotein particle
      subfractions and cardiovascular disease events].
AB  - OBJECTIVE: High-density lipoprotein cholesterol (HDL-C) has cardio-protective
      effects. However, results from clinical trials showed that improving HDL-C levels
      alone did not reduce the cardiovascular disease (CVD) events and different HDL
      particles (HDL-P) subfractions may relate to different CVD risk. In this meta
      analysis, we reviewed prospective studies reported relationships of HDL-P
      subfractions with CVD risk. METHODS:  DATA SOURCES: MEDLINE, Cochrane Library and
      China National Knowledge Infrastructure (CNKI) were searched up to July 1st,
      2013. STUDY SELECTION: Prospective studies that reported an association of HDL-P
      subfractions with the incidence of CVD were included and studies did not assess
      the hazard ratio, relative risk, or odds ratio of HDL-P and studies did not
      adjust for any other risk factors were excluded. DATA EXTRACTION AND SYNTHESIS:
      All studies were extracted by 1 researcher and verified by another researcher.
      Full data were extracted from the studies meanwhile the quality was evaluated.
      Heterogeneity was analyzed. Pooled relative risk (RR) and 95% confidence interval
      were calculated. RESULTS: Six studies were enrolled in this meta-analysis. HDL-P
      can be grouped into three subfractions: large HDL-P, medium HDL-P and small HDL
      P. Only higher large HDL-P concentration was associated with decreased risk for
      CVD and pooled RR was 0.65 (95%CI:0.55-0.76). Medium HDL-P and small HDL-P were
      not associated with the incidence of CVD events. CONCLUSION: Higher large HDL-P
      concentration is associated with lower CVD risk. Assessment of HDL-P subfractions
      may thus be of great clinical importance for evaluating the CVD risk.

PMID- 24680273
TI  - [A case report of coronary stenting induced psychiatric symptoms].

PMID- 24680275
TI  - [Mapping, verification and ablation of one patient after ablation of persistent
      atrial fibrillation recurrence regular left atrial polycyclic reentry atrial
      tachycardia].

PMID- 24680274
TI  - [Alcohol septal ablation for obstructive hypertrophic cardiomyopathy in two
      patients with Sigmoid-shaped ventricular septum].

PMID- 24680276
TI  - [Acute inferior and right ventricular myocardial infarction in a teenager with
      nephrotic syndrome].

PMID- 24680277
TI  - [An aged patient with atrial septal defect].

PMID- 24680278
TI  - [Value of propensity score method in percutaneous coronary intervention studies].

PMID- 24680279
TI  - [Progress of trans-radial approach for percutaneous coronary intervention].

PMID- 24680280
TI  - [The current status and prospective application of fractional flow reserve CT
      imaging].

PMID- 24680281
TI  - Lack of donor and recipient age interaction in cardiac transplantation.
AB  - BACKGROUND: The proportion of older donors and recipients is constantly rising in
      heart transplantation (HTX). The impact of age on different outcomes after HTX
      has been studied; however, effects of interaction between donor and recipient age
      remain elusive. METHODS: This retrospective cohort study comprised 1,190 patients
      who underwent HTX between 1984 and 2011 at the Medical University Vienna.
      Multivariable models consisted of a basic set that included donor age, recipient
      age, and transplant eras and were adjusted for 2 sets of 6 possible confounders
      and 3 mediator variables. Cox models were used to estimate the risk of death. To
      search for age-related effects on the development of cardiac allograft
      vasculopathy (CAV), we applied cause-specific Cox models and proportional sub
      distribution hazard models for competing risk data. RESULTS: Survival was 80%,
      77%, 69%, and 56% after 1, 2, 5, and 10 years, respectively. Donor age (hazard
      ratio [HR], 1.1; 95% confidence interval [CI], 1.0-1.2), recipient age (HR, 1.1;
      95% CI, 1.0-1.2), admission from intensive care unit to HTX (HR, 1.5; 95% CI, 1.2
      1.9), and diabetes (HR, 1.4; 95% CI, 1.1-1.7) were identified as significant
      independent risk factors for death. Significant risk factors for CAV were donor
      age (HR, 1.4; 95% CI, 1.3-1.5) and male recipient sex (HR, 1.5; 95% CI, 1.0-2.2).
      Recipient age was inversely associated with initiation of CAV (HR, 0.8; 95% CI,
      0.8-1.0). Analysis of the interaction between donor and recipient age was not
      significant for death (p = 0.8) or CAV (p = 0.6). CONCLUSIONS: We found no
      interaction between donor and recipient age negatively affecting mortality and
      CAV. The identified independent risk factors may have implications for allocation
      strategies in elderly recipients.

PMID- 24680282
TI  - Molecular analysis of Oenococcus oeni and the relationships among and between
      commercial and autochthonous strains.
AB  - The presence and distribution of genotypes from malolactic starter cultures
      between the autochthonous microbiota in fermenting Rioja wines have been studied
      in this paper. The commercial cultures characterization allowed to identify
      different species and common pulsed field gel electrophoresis and randomly
      amplified polymorphic DNA genotypes in several brands of Oenococcus oeni starter
      cultures. Four indistinguishable genotypes were found between the commercial and
      the autochthonous O. oeni strains. These four genotypes appeared during different
      vintages in seven of the 10 sampled wineries despite bacterial starter cultures
      had never been used. Therefore, the detection of commercial LAB genotypes
      indistinguishable from the autochthonous ones involved their removal from a
      selection process. These genotypes represented the 17.7% of autochthonous O. oeni
      isolated in this region during three consecutive years. This fact demonstrated
      that performing similar studies as previous selection criteria is advisable to
      avoid large work and the proposal of one commercialized bacteria.

PMID- 24680283
TI  - Metabolic distance estimation based on principle component analysis of metabolic
      turnover.
AB  - Visualization of metabolic dynamism is important for various types of metabolic
      studies including studies on optimization of bio-production processes and studies
      of metabolism-related diseases. Many methodologies have been developed for
      metabolic studies. Among these, metabolic turnover analysis (MTA) is often used
      to analyze metabolic dynamics. MTA involves observation of changes in the
      isotopomer ratio of metabolites over time following introduction of isotope
      labeled substrates. MTA has several advantages compared with (13)C-metabolic flux
      analysis, including the diversity of applicable samples, the variety of isotope
      tracers, and the wide range of target pathways. However, MTA produces highly
      complex data from which mining useful information becomes difficult. For easy
      understanding of MTA data, a new approach was developed using principal component
      analysis (PCA). The resulting PCA score plot visualizes the metabolic distance,
      which is defined as distance between metabolites on the real metabolic map. And
      the score plot gives us some hints of interesting metabolism for further study.
      We used this method to analyze the central metabolism of Saccharomyces cerevisiae
      under moderated aerobic conditions, and time course data for 77 isotopomers of 14
      metabolites were obtained. The PCA score plot for this dataset represented a
      metabolic map and indicated interesting phenomena such as activity of fumarate
      reductase under aerated condition. These findings show the importance of a
      multivariate analysis to MTA. In addition, because the approach is not biased,
      this method has potential application for analysis of less-studied pathways and
      organisms. 

PMID- 24680284
TI  - Effect of plasma-irradiated silk fibroin in bone regeneration.
AB  - We have recently identified plasma-irradiated silk fibroin (P-AF) as a key
      regulator of bone matrix properties and composition. Bone matrix properties were
      tested in 48 femur critical size defects (3.25 mm in diameter) with the
      expression of osteoblast specific genes at 1 and 2 weeks after surgery. The
      scaffolds were characterized by various states of techniques; the scanning
      electronic microcopy revealed the large sized pores in the aqueous-based silk
      fibroin (A-F) scaffold and showed no alteration into the architecture by the
      addition of plasma irradiation. The contact angle measurements confirmed the
      introduction of plasma helped to change the hydrophobic nature into hydrophilic.
      The histological analyses confirmed the presence of silk fibroin in scaffolds and
      newly formed bone around the scaffolds. Immunohistochemical examination revealed
      the increased expression pattern in a set of osteoblast specific genes (TGF-beta,
      TGF-beta type III receptor, Runx2, type I collagen and osteocalcin). These data
      were the first to show that the properties of bone matrix are regulated,
      specifically through Runx2 pathway in P-AF group. Thus, an employment of P-AF
      increases several compositional properties of bone, including increased bone
      matrix, mineral concentration, cortical thickness, and trabecular bone volume.

PMID- 24680286
TI  - Expression and detection of estrus in dairy cows: the role of new technologies.
AB  - Despite the widespread adoption of hormonal synchronization protocols that allow
      for timed artificial insemination (AI), detection of estrus plays an important
      role in the reproductive management program on most dairies in the United States.
      Increased physical activity is a secondary sign of estrus in dairy cattle, and a
      new generation of electronic systems that continuously monitor physical activity
      to predict timing of AI have been developed and marketed to the dairy industry. A
      variety of management and physiologic challenges inhibit detection of behavioral
      estrus on farms, but the prevalence of anouvular cows near the end of the
      voluntary waiting period is particularly problematic. Only 70% of lactating
      Holstein cows were detected in estrus when using an activity monitoring system,
      with the remaining 20% of cows classified as anovular and 10% ovulating without
      showing signs of activity. Mean time of AI in relation to ovulation based on the
      activity monitoring system was acceptable for most of the cows with increased
      activity, however, variability in the duration of estrus and timing of AI in
      relation to ovulation could result in poor pregnancy outcomes in some cows. Use
      of a Presynch-Ovsynch protocol for submission of cows for first AI has been
      widely adopted by dairies in the United States, and a combined approach in which
      AI based on activity is followed by submission of cows not detected with activity
      to timed AI after synchronization of ovulation may be an effective strategy for
      submission of cows to first AI. Based on a field trial on a large commercial
      dairy in the United States, the activity monitoring system detected 70% of cows
      with increased activity after the second PGF2alpha injection of a Presynch
      Ovsynch protocol, however, cows inseminated to increased activity had fewer
      pregnancies per AI (P/AI) compared with cows with increased activity after the
      second PGF2alpha injection that received timed AI after completing the Presynch
      Ovsynch protocol. Based on an economic model comparing reproductive management
      programs with varying levels of AI to estrus v. timed AI, the rate of estrus
      detection and the P/AI to inseminations based on AI to detected estrus v. timed
      AI affected the decision to inseminate based on activity v. timed AI. In
      conclusion, an activity monitoring system detected increased activity in about
      70% of lactating Holstein cows on a large commercial dairy in the United States,
      however, synchronization of ovulation and timed AI was beneficial to inseminate
      cows not detected with increased activity by the activity monitoring system. 

PMID- 24680285
TI  - Complete ON/OFF photoswitching of the motility of a nanobiomolecular machine.
AB  - To apply motor proteins as natural nanomolecular machines to transporting systems
      in nanotechnology, complete temporal control over ON/OFF switching of the
      motility is necessary. We have studied the photoresponsive inhibition properties
      of azobenzene-tethered peptides for regulation of kinesin-microtubule motility.
      Although a compound containing a peptide having an amino acid sequence derived
      from the kinesin's C-terminus (a known inhibitor of kinesin's motor domain) and
      also featuring a terminal azobenzene unit exhibited an inhibition effect, the
      phototunability of this behavior upon irradiation with UV or visible light was
      only moderate. Unexpectedly, newly synthesized peptides featuring the reverse
      sequence of amino acids of the C-terminus of kinesin exhibited excellent
      photoresponsive inhibition. In particular, azobenzene-CONH-IPKAIQASHGR completely
      stopped and started the motility of kinesin-microtubules in its trans- and cis
      rich states, respectively, obtained after irradiation with visible and UV light,
      respectively. A gliding motility system containing this photoresponsive inhibitor
      allowed in situ control of the motion of microtubules on a kinesin-coated glass
      substrate. It is expected that the present results on the photoresponsive
      nanomotor system open up new opportunities to design nanotransportation systems. 

PMID- 24680288
TI  - Lateral antebrachial cutaneous nerve compression after traumatic rupture of the
      long head of the biceps: a case series.
AB  - BACKGROUND: Lateral antebrachial cutaneous (LABC) nerve compression is a rare but
      debilitating injury. There are limited data on the association of LABC nerve
      compression and proximal biceps rupture. We theorized that because of distal
      migration, the biceps muscle and tendon cause compression on the nerve. METHODS:
      We present 2 cases in which patients had proximal biceps ruptures with tendon
      retraction and developed neurologic symptoms associated with the LABC nerve. To
      demonstrate our theory, we performed a cadaveric experiment. After making an
      incision to expose the entire biceps muscle and the musculocutaneous nerve and
      its branch into the LABC nerve, we marked each structure in 2-cm increments with
      a marking pen. The long head of the biceps was then cut to simulate a proximal
      biceps rupture. RESULTS: The relationship between the 3 structures was then
      studied, showing no change in position of the musculocutaneous nerve or LABC
      nerve. The biceps muscle and tendon had migrated distally toward the LABC nerve,
      demonstrating compression of the nerve. CONCLUSION: Proximal biceps tears
      commonly occur from trauma as well as iatrogenically after a biceps tenotomy for
      treatment of biceps tendinopathy. However, it is unusual for neuropathy of the
      LABC nerve to occur. Patients who develop neuropathy associated with the LABC
      nerve after a proximal biceps rupture can be effectively treated with LABC nerve
      decompression and biceps plasty. We found that this was an effective surgical
      treatment of LABC neuropathy without the need for proximal biceps tenodesis.

PMID- 24680287
TI  - Preoperative CA 15-3 levels predict the prognosis of nonmetastatic luminal A
      breast cancer.
AB  - BACKGROUND: The prognostic value of serum tumor markers (STMs) in nonmetastatic
      breast cancer patients with different molecular subtypes (luminal A, luminal B,
      and nonluminal) remains unknown. It is our institutional policy to assess the
      STMs in nonmetastatic patients. This retrospective single-center study is to
      investigate the association between STMs and clinical outcomes in nonmetastatic
      patients and the impact of molecular subtypes. METHODS: A total of 368 patients
      with available clinical outcomes, tumor node metastasis stages, and STMs levels
      were included. The serum level of preoperative STMs (carcinoembryonic antigen
      [CEA], cancer antigen 125 [CA-125], and cancer antigen 15-3 [CA 15-3]) was
      analyzed and compared among distinct molecular subtypes. Univariate and
      multivariate analyses were used to investigate the relationship among STMs
      concentrations and patient outcomes. RESULTS: The median levels of CA 15-3 were
      10.2, 8.1 and 7.1 U/mL in patients with luminal A, luminal B, and nonluminal
      diseases, respectively (P = 0.015). The levels of CEA and CA-125 were similar
      among the subtypes. Multivariate analysis showed that higher CA 15-3 was
      significantly associated with worse clinical outcomes exclusively in luminal A
      patients (P = 0.033 for metastasis-free survival and P = 0.030 for relapse-free
      survival). In contrast, higher CEA was a significant prognostic factor for worse
      clinical outcomes (P = 0.003 for metastasis-free survival and P = 0.015 for
      metastasis-free survival) in nonluminal groups. CONCLUSIONS: The prognostic value
      of preoperative STMs may be different among molecular subtypes. Patients with
      luminal A diseases had higher levels of CA 15-3. Higher preoperative CA 15-3 was
      associated with worse clinical outcomes exclusively in patients with luminal A
      diseases.

PMID- 24680289
TI  - Encoded protein from ycbR gene of enterohemorrhagic Escherichia coli O157:H7
      associated with adherence to HEp-2 cells.
AB  - Adhesion is one of the significant virulence factors in enterohemorrhagic
      Escherichia coli (EHEC) O157:H7 pathogenesis. It is regulated by specific loci in
      the genome sequence. This study mainly focused on investigating the influence of
      ycbR gene and its encoded YCBR protein on the adhesion of EHEC O157:H7 to HEp-2
      cells. In the first part, mutants of EHEC O157:H7 were constructed through TnphoA
      mutagenesis and assayed for adherent ability. Six mutant strains with lost
      adherence to HEp-2 cells were isolated and then sequenced using a primer that
      hybridized to phoA sequence downstream of the fusion joint. The sequencing
      results indicated that the gene of eae and ycbR, between the initiation codon and
      the -10 sequence of Z4182, yciI, ARAC-type regulator protein, and high-affinity
      gluconate transporter of EHEC were all possibly related to adhesion. Of the six
      genes, the ycbR gene was cloned to the pET28a vector to analyze its function
      further. Recombinant YCBR protein fused to a His tag (YCBR-His) was expressed
      under IPTG induction and purified by Ni-NTA column. The purified protein was
      subcutaneously injected to rabbits to prepare antisera. The results of an
      adherence assay in the presence of anti-YCBR-His antibodies indicated that
      antibodies blocked the adherence of EHEC O157:H7 to HEp-2 cells. These
      observations suggested that ycbR encoded a novel adherence-associated determinant
      of EHEC O157:H7, which could contribute to the adhesive capacity of the bacteria.

PMID- 24680290
TI  - Functional immunocytochemistry of Tragulus placenta: implications for ruminant
      evolution.
AB  - INTRODUCTION AND METHODS: Tragulus, the mouse deer, is considered the most
      primitive ruminant, with a diffuse placenta grossly quite unlike the cotyledonary
      type of the other ruminants. This immunocytochemical investigation of placental
      transporters was designed to elucidate possible mechanisms of evolution to the
      cotyledonary form. RESULTS AND DISCUSSION: Tragulus expresses several of the
      major transport systems characteristic of the ruminants: the trophoblast
      binucleate cell (BNC) dynamics, the requirement for two isoforms, GT1 and GT3,
      for glucose transport, the provision of Aquaporin 3 for water control, and
      uterine milk and histiotrophic secretion from uterine glands. However whereas the
      expression of the 9 kD Calcium Binding Protein (9 CBP) for calcium transport in
      ruminants is restricted to the intercotyledonary trophoblast with its areolae,
      Tragulus, having no intercotyledonary area, expresses 9 CBP throughout the villus
      trophoblast. There is some localised development of areolar-like structures in
      the mid term Tragulus but it is insignificant at term. The strong expression of
      Glucose Transporter 1 (GT1) in the BNC granules is unique to Tragulus.
      CONCLUSION: Tragulus relies on essentially similar transport and BNC dynamics as
      the other ruminants. Thus the evolutionary pressures driving the development of
      the cotyledonary placenta probably lie in the increase in body size and the
      consequent need for a larger placental area to ensure sufficient glucose for the
      fetus. The delivery in Tragulus of GT1 to the maternal facing side may be this
      species unique solution to maintain the glucose supply.

PMID- 24680291
TI  - Roles of glucocorticoids in human parturition: a controversial fact?
AB  - The pivotal role of glucocorticoids in the initiation of parturition has been
      very well documented in several domestic mammalian animal species. However the
      role of glucocorticoids in human parturition remains controversial mainly because
      of the absence of effect of synthetic glucocorticoids, given to promote fetal
      organ maturation in pregnant women with threatened preterm delivery, on the
      length of gestation. This article will review studies of glucocorticoids in human
      parturition and provide evidence for an important role of glucocorticoids in
      human parturition as well but a simultaneous high concentration of estrogen
      within the intrauterine tissues may be necessary for GCs to initiate parturition.
      The synthetic GCs dexamethasone and betamethasone pass through the placenta
      intact resulting in potent negative feedback on the fetal HPA axis and diminished
      production of DHEA from fetal adrenal glands for estrogen synthesis by the
      placenta. This may negate the effect of systemic administration of GCs on the
      induction of labor, especially in cases where the myometrium is not yet fully
      primed by estrogen. Endogenous glucocorticoids are inactivated by the placental
      11beta-HSD2 thus limiting the negative feedback of maternal cortisol on the fetal
      HPA axis and allowing the simultaneous rise of cortisol and estrogen levels
      towards the end of gestation. Therefore, endogenous glucocorticoids, particularly
      glucocorticoids produced locally in the intrauterine tissues may play an
      important role in parturition in humans by enhancing prostaglandin production in
      the fetal membranes and stimulating estrogen and CRH production in the placenta. 

PMID- 24680292
TI  - The role of veno-venous anastomoses in twin-twin transfusion syndrome.
AB  - The aim of this study was to investigate the independent role of veno-venous (VV)
      anastomoses in the development of twin-twin transfusion syndrome (TTTS). Thirty
      TTTS placentas and 41 non-TTTS placentas, routinely injected with colored dye,
      were enrolled in this study. We excluded all cases with arterio-arterial (AA)
      anastomoses and TTTS cases treated with laser surgery. The prevalence of VV
      anastomoses was significantly higher in TTTS cases compared to non-TTTS cases,
      37% (11/30) and 7% (3/41), respectively (P < .01; odds ratio 7.3; 95% confidence
      interval: 1.8-37.1). Our findings suggest that, in the absence of AA anastomoses,
      VV anastomoses may enhance the development of TTTS.

PMID- 24680293
TI  - Pre infusion, post thaw CD34+ peripheral blood stem cell enumeration as a
      predictor of haematopoietic engraftment in autologous haematopoietic cell
      transplantation.
AB  - INTRODUCTION: By convention, peripheral blood stem cell products for autologous
      transplantation are evaluated for quality by CD34(+) cell dose at the time of
      harvesting. A CD34(+) cell dose in excess of 2.0 * 10(6)/kg of recipient body
      weight is considered adequate for haematopoietic engraftment. Viable CD34(+) cell
      numbers are enumerated in most laboratories using the ISHAGE single platform flow
      cytometric method which utilizes monoclonal antibodies to CD45, CD34 and 7 amino
      actinomycin D (7AAD) dye exclusion. METHODS: One hundred and six consecutive
      autologous transplantation procedures underwent viable CD34(+) cell enumeration
      at the time of harvesting and post thaw prior to re-infusion. Neutrophil and
      platelet engraftment and markers of haematopoietic support were analyzed.
      RESULTS: Mean pre-cryopreservation viable CD34(+) numbers were 4.882 * 10(6)/kg.
      Mean post thaw viable CD34(+) numbers were 3.234 * 10(6)/kg. Mean loss of viable
      CD34(+) cells with processing and cryo-preservation was 1.648 * 10(6)/kg (33%).
      For neutrophil engraftment, there was no significant difference between high (?
      3.0 * 10(6)/kg) and low (<1.5 * 10(6)/kg) post thaw viable CD34(+) cell counts
      (p=0.545). For platelet engraftment, there was however a significant difference
      observed between the high and low pre infusion viable CD34(+) groups (p<0.001).
      Additionally, significant differences were seen between the post thaw viable
      CD34(+) cell count and the associated length of hospital admission, days of use
      of G-CSF post transplantation, use of antibiotics in the post transplantation
      period and transfusion support in the post transplantation period. CONCLUSION: A
      significant loss of viable CD34(+) cells occurs during processing,
      cryopreservation and thawing. Low numbers of viable CD34(+) cells infused post
      thaw will still result in adequate neutrophil engraftment however may delay
      platelet engraftment. Low viable CD34(+) cell numbers have significant effects on
      admission duration and use of haematopoietic supportive measures with consequent
      effects on healthcare resources.

PMID- 24680294
TI  - Validation of the diagnosis canine epilepsy in a Swedish animal insurance
      database against practice records.
AB  - Canine epilepsy is one of the most common neurological conditions in dogs but the
      actual incidence of the disease remains unknown. A Swedish animal insurance
      database has previously been shown useful for the study of disease occurrence in
      companion animals. The dogs insured by this company represent a unique population
      for epidemiological studies, because they are representative of the general dog
      population in Sweden and are followed throughout their life allowing studies of
      disease incidence to be performed. The database covers 50% of all insured dogs
      (in the year 2012) which represents 40% of the national dog population. Most
      commonly, dogs are covered by both veterinary care insurance and life insurance.
      Previous studies have shown that the general data quality is good, but the
      validity of a specific diagnosis should be examined carefully before using the
      database for incidence calculations. The aim of the current study was therefore
      to validate the information contained in the insurance database regarding canine
      epilepsy. The validation focused on the positive predictive value and the data
      transfer from the veterinary practice records to the insurance database. The
      positive predictive value was defined as the proportion of recorded cases that
      actually had the disease in question. The quality of the data-transfer was
      assessed by comparing the diagnostic codes in practice records to the codes in
      the insurance database. The positive predictive value of the diagnostic codes for
      canine epilepsy (combining "epileptic convulsions" and "idiopathic epilepsy") in
      the insurance database was validated in a cross-sectional study where insurance
      claims for canine epilepsy were compared to diagnostic information in practice
      records. A random sample of dogs with a reimbursed insurance claim during 2006
      was included in the study sample (n=235). Practice records were requested by mail
      from attending veterinarians. Two independent examiners scrutinized all the
      records. All 235 dogs were coded correctly in the database as they really had
      suffered seizures with or without convulsions, and the quality of the data
      transfer was therefore excellent. In total, 167 dogs (71%) were classified as
      cases of canine epilepsy according to pre-defined criteria, and the positive
      predictive value was therefore considered relatively high. Based on these
      results, it was concluded that the data regarding canine epilepsy in the
      insurance database can be used for further population studies. 

PMID- 24680295
TI  - High-frequency intra-operative ultrasound-guided surgery of superficial intra
      cerebral lesions via a single-burr-hole approach.
AB  - The study described here examined the feasibility of using high-frequency intra
      operative ultrasound (hfioUS) guidance to resect superficial intra-cerebral
      lesions through a single burr hole. A cohort of 23 consecutive patients with a
      total of 24 intra-cerebral lesions (9 intra-cerebral metastases, 8 gliomas, 4
      infections, 2 lymphomas and 1 cavernoma) were studied. All lesions could be
      localized and successfully resected, biopsied or aspirated, and histopathological
      diagnoses were obtained in all cases. The mean operating time was 59.6 +/- 23.9
      min. The mean cross-sectional lesion size was 6.4 +/- 7.6 cm(2), and the mean
      cortex surface-to-lesion distance was 0.6 +/- 0.8 cm. Our results illustrate the
      feasibility of identifying and resecting superficial intra-cerebral lesions under
      hfioUS guidance via a single-burr-hole approach. We were able to achieve short
      resection times with no post-operative complications in all patients, favorable
      conditions under which to start adjuvant therapy when indicated. 

PMID- 24680296
TI  - Change: a constant in orthopaedics.

PMID- 24680298
TI  - Authors' reply.

PMID- 24680299
TI  - Comment on anterior cruciate ligament reconstruction with autografts compared
      with non-irradiated non-chemically treated allografts.

PMID- 24680300
TI  - Mesenchymal stem cells versus fat pad-derived cells.

PMID- 24680301
TI  - Authors' reply.

PMID- 24680302
TI  - Arthroscopic Bankart repair using knot-tying versus knotless suture anchors: is
      there a difference?
AB  - PURPOSE: To compare the clinical outcome between the use of knotless sutures
      versus knot-tying sutures in arthroscopic Bankart repairs. METHODS: Between
      January 2007 and January 2011, 87 patients who underwent arthroscopic Bankart
      repair with the use of knot-tying suture anchors or knotless suture anchors were
      evaluated, with 45 patients in the knot-tying suture group and 42 patients in the
      knotless group. Patients were assigned to either group, with odd-numbered
      patients going to the knot-tying suture arm and even-numbered patients assigned
      to the knotless arm. Outcomes included the Constant score, the visual analog
      scale (VAS) score, patient satisfaction score, and range of motion in forward
      flexion and external rotation with the arm in adduction. Redislocations or
      subluxations with the 2 techniques was also studied. RESULTS: Both groups showed
      a statistically significant improvement between the preoperative and
      postoperative VAS scores and Constant scores. In the knot-tying suture group, the
      VAS score improved from 2.5 +/- 2.3 to 0.7 +/- 0.5 (P < .05) and the Constant
      score improved from 64 +/- 7 to 92 +/- 10 (P < .05). In the knotless group, the
      VAS score improved from 2.8 +/- 2.5 to 0.9 +/- 0.6 (P < .05), and the Constant
      score improved from 62 +/- 6 to 89 +/- 9 (P < .05). The patient satisfaction
      scores were 6.9 and 7.1 for the knot tying and knotless groups, respectively. No
      statistically significant differences were found when comparing the outcomes
      between the 2 groups. The change in the range of forward flexion and external
      rotation was also similar in the 2 groups. There was also no difference in
      recurrence or redislocation rates. CONCLUSIONS: Both the knot-tying and knotless
      suture anchors groups showed statistically significant and similar improvement in
      VAS and Constant scores. Both anchors provided reasonable outcomes. The knotless
      suture anchor is a good alternative to knot-tying suture anchors so that
      arthroscopic Bankart repairs can be performed without knot tying. LEVEL OF
      EVIDENCE: Level II, prospective comparative study.

PMID- 24680303
TI  - Does autologous leukocyte-platelet-rich plasma improve tendon healing in
      arthroscopic repair of large or massive rotator cuff tears?
AB  - PURPOSE: To evaluate the clinical and magnetic resonance imaging (MRI) outcome of
      arthroscopic rotator cuff repair with the use of leukocyte-platelet-rich plasma
      (L-PRP) in patients with large or massive rotator cuff tears. METHODS: A
      comparative cohort of patients with large or massive rotator cuff tears
      undergoing arthroscopic repair was studied. Two consecutive groups of patients
      were included: rotator cuff repairs with L-PRP injection (group 1, n = 35) and
      rotator cuff repairs without L-PRP injection (group 2, n = 35). A double-row
      cross-suture cuff repair was performed by a single surgeon with the same
      rehabilitation protocol. Patients were clinically evaluated with the Constant
      score; Simple Shoulder Test score; University of California, Los Angeles (UCLA)
      score; and strength measurements by use of a handheld dynamometer. Rotator cuff
      healing was evaluated by postoperative MRI using the Sugaya classification (type
      1 to type 5). RESULTS: We prospectively evaluated the 2 groups at a minimum 2
      year follow-up. The results did not show differences in cuff healing between the
      2 groups (P = .16). The size of recurrent tears (type 4 v type 5), however, was
      significantly smaller in group 1 (P = .008). There was no statistically
      significant difference in the recurrent tear rate (types 4 and 5) between the 2
      groups (P = .65). There was no significant difference between group 1 and group 2
      in terms of University of California, Los Angeles score (29.1 and 30.3,
      respectively; P = .90); Simple Shoulder Test score (9.9 and 10.2, respectively; P
      = .94); Constant score (77.3 and 78.1, respectively; P = .82); and strength (7.5
      and 7.0, respectively; P = .51). CONCLUSIONS: In our study the use of autologous
      L-PRP did not improve the quality of tendon healing in patients undergoing
      arthroscopic repair of large or massive rotator cuff tears based on postoperative
      MRI evaluation. The only significant advantage was that the L-PRP patients had
      smaller iterative tears. However, the functional outcome was similar in the 2
      groups of patients. LEVEL OF EVIDENCE: Level III, case-control study.

PMID- 24680304
TI  - Primary versus revision arthroscopic reconstruction with remplissage for shoulder
      instability with moderate bone loss.
AB  - PURPOSE: This study aims to evaluate our outcomes of arthroscopic remplissage in
      this setting. METHODS: A retrospective review was performed to identify patients
      who underwent arthroscopic remplissage of an engaging Hill-Sachs lesion along
      with anterior capsulolabral reconstruction for anterior glenohumeral instability
      with moderate glenohumeral bone loss at our institution. Thirty-five patients,
      with a minimum of 2 years' follow-up, were identified. We assessed the American
      Shoulder and Elbow Surgeons score, incidence of recurrent instability, and
      postoperative Rowe instability score. RESULTS: Follow-up was available for 30
      patients (31 shoulders). The mean age was 24.6 years, with a mean follow-up
      period of 41 months. Prior instability surgery had failed in 11 patients, and
      they underwent capsulolabral reconstruction and remplissage ("revision surgery").
      The failure rate in revision cases (36%) was significantly higher than the
      failure rate in primary surgery cases (0%) (P = .01). Failure resulted from
      trauma in all 4 patients, and none required further surgery. The mean American
      Shoulder and Elbow Surgeons score for all patients improved from 50
      preoperatively to 91 postoperatively (P < .001), with no significant
      postoperative difference between primary and revision patients (P = .13). The
      patients with clinical failure showed nonsignificant improvement from 41
      preoperatively to 72 postoperatively (P = .08). The mean postoperative Rowe score
      for the entire cohort was 90. The Rowe score was significantly lower in the 4
      cases of failure than in the 27 non-failure cases (51 v 96, P < .001).
      CONCLUSIONS: In our experience, aggressive capsulolabral reconstruction with
      remplissage in traumatic instability patients with moderate bone loss and
      engaging humeral Hill-Sachs lesions yields acceptable outcomes for primary
      instability surgery. However, a significantly higher failure rate occurred when
      arthroscopic reconstruction with remplissage was performed in the revision
      setting. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24680305
TI  - The wrist insufflation test: a confirmatory test for detecting intercarpal
      ligament and triangular fibrocartilage complex tears.
AB  - PURPOSE: The purpose of this study was to determine the accuracy of the wrist
      insufflation test based on mean radiocarpal and midcarpal joint space volumes.
      METHODS: Twenty-nine patients underwent 3-4 portal radiocarpal and radial
      midcarpal portal insufflation before wrist arthroscopy. The volume remaining in
      the radiocarpal space at equilibrium was recorded, and the contour of the dorsal
      wrist and distal radioulnar joint was palpated for a fluid wave. After
      insufflation, wrist arthroscopy was performed and diagnoses were recorded. The
      mean volumes of the intact radiocarpal and midcarpal spaces were then compared
      with those of the compromised radiocarpal and midcarpal spaces to determine the
      overall sensitivity and specificity of the test. RESULTS: A total of 29 patients
      (18 male and 11 female) underwent wrist insufflation before wrist arthroscopy.
      The mean age of the patients was 42 years (range, 17 to 69 years). Intact
      radiocarpal spaces accepted a mean of 3.5 +/- 0.16 mL of fluid, whereas
      compromised radiocarpal spaces accepted a mean of 5.5 +/- 0.48 mL of fluid (P <
      .01; 95% confidence interval, 2.87 to 3.30). Intact midcarpal spaces accepted a
      mean of 2.5 +/- 0.18 mL, whereas compromised midcarpal spaces accepted a mean of
      5.6 +/- 0.38 mL (P < .01; 95% confidence interval, 1.70 to 2.30). The overall
      sensitivity of the test was 83.3%, and the overall specificity was 100%.
      CONCLUSIONS: Complete scapholunate interosseous ligament and triangular
      fibrocartilage complex tears can be detected when there is an increased
      radiocarpal joint space volume with insufflation through the 3-4 portal combined
      with a fluid wave over the radial midcarpal space or the distal radioulnar joint.
      Complete scapholunate interosseous ligament and lunotriquetral interosseous
      ligament tears can also be detected when there is an increased midcarpal space
      volume with insufflation through the radial midcarpal portal combined with a
      fluid wave over the radial radiocarpal space or the ulnar radiocarpal space.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24680306
TI  - Radiographic, histologic, and arthroscopic findings in amorphous calcifications
      of the hip labrum.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical, radiographic,
      histologic, and intraoperative findings of an amorphous calcification involving
      the acetabular labrum. METHODS: From October 2008 to April 2013, all patients who
      underwent arthroscopic hip surgery for symptomatic intra-articular hip disorders
      and were found to have the characteristic calcific deposit involving the
      acetabular labrum were included. These patients were reviewed retrospectively on
      prospectively collected data. Radiographs were retrospectively evaluated for
      morphologic features of impingement and characteristics of labral calcification.
      RESULTS: Sixteen patients were identified as having amorphous calcification at
      the time of arthroscopy. There were 15 women and 1 man. Mean age was 37.3 years
      (range, 30 to 50 years). Symptoms were present for a mean of 9.3 months (range, 3
      to 48 months). All patients reported anterior groin pain. Fifteen (94%) patients
      had positive anterior impingement and 9 (56%) had positive results for lateral
      impingement. Calcifications measured on average 3.2 mm (range, 1.9 mm to 5.6 mm),
      and 14 had a clear separation from the rim with increased opacity compared with
      neighboring trabecular bone. Intraoperatively, the characteristic amorphous
      calcium deposit was located in the anterosuperior labrum, with the deposit found
      to be accessible from the capsule-labral recess in all cases. All patients had
      labral tears and all patients had at least one component of femoroacetabular
      impingement (FAI). CONCLUSIONS: Calcification in the anterosuperior acetabular
      labrum presents with a consistent patient demographic and distinct radiographic
      and arthroscopic presentation that is different from os acetabuli. As with os
      acetabuli, one should have a high suspicion for FAI when this lesion is
      encountered. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 24680307
TI  - Efficacy of magnetic resonance imaging evaluation for meniscal tear in acute
      anterior cruciate ligament injuries.
AB  - PURPOSE: The objective of this study was to compare the preoperative magnetic
      resonance imaging (MRI) diagnostic rates of meniscal injuries combined with acute
      anterior cruciate ligament (ACL) injuries, as well as traumatic meniscal injuries
      without ACL injuries. METHODS: From January 2005 through April 2013, 208 patients
      who underwent ACL reconstruction and 1,334 patients with traumatic meniscal tear
      injuries were examined by MRI and arthroscopy. Patients with chronic ACL
      injuries, revisions, fracture histories, or multiple-ligament injuries and
      patients with Outerbridge degenerative changes of grade 3 or greater were
      excluded, yielding 159 patients and 621 patients in the 2 groups, respectively.
      The medial meniscus (MM) and lateral meniscus (LM) examined by MRI and
      arthroscopy for findings of tears were compared in each group. The sensitivity,
      specificity, positive predictive value, and negative predictive value for MM and
      LM tears by MRI were compared and analyzed statistically. RESULTS: The diagnostic
      sensitivity of MRI in the group with ACL injury was significantly lower than that
      in the ACL-intact group for the MM (P < .001) and LM (P = .040). The negative
      predictive value was also lower in the group with ACL injury for both the MM (P =
      .008) and LM (P < .001). There was no statistical difference in specificity and
      positive predictive value between the 2 groups. CONCLUSIONS: This study showed
      that if a patient had an acute ACL tear, the sensitivity and negative predictive
      value of MRI for a meniscal tear were less than if there was no ACL tear, which
      led to the low diagnostic accuracy of MRI. LEVEL OF EVIDENCE: Level III,
      retrospective case-control study.

PMID- 24680308
TI  - Revision rates after anterior cruciate ligament reconstruction using bone
      patellar tendon-bone allograft or autograft in a population 25 years old and
      younger.
AB  - PURPOSE: To compare clinical outcomes and revision rates for anterior cruciate
      ligament (ACL) reconstructions using bone-patellar tendon-bone (BPTB) allografts
      versus BPTB autografts in a population of patients aged 25 years and younger.
      METHODS: A consecutive series of patients 25 years or younger undergoing ACL
      reconstruction with either a patient-selected BPTB allograft or BPTB autograft
      fixed with biocomposite interference screws was retrospectively reviewed.
      Multiligamentous and posterior cruciate ligament tears were excluded. All
      allografts were from a single source and not chemically processed or irradiated.
      Two graft-specific rehabilitation programs were used. The primary outcome measure
      was graft failure. Failure was defined as a subsequent ACL revision surgery, 2+
      Lachman test, positive pivot-shift, or side-to-side KT difference of greater than
      5 mm. Secondary outcome measures included Cincinnati, Lysholm, and International
      Knee Documentation Committee (IKDC) activity scores. RESULTS: In 81 patients at
      least 24 months after surgery (28 allografts; 53 autografts), 7 failures were
      identified: 2 of 28 (7.1%) allografts and 5 of 53 (9.4%) autografts. Mean
      Cincinnati scores improved from 54.6 and 39.5 (allografts and autografts,
      respectively) to 86.2 and 85.1. Mean Lysholm scores improved from 60.3 and 44.8
      (allografts and autografts, respectively) to 89.9 and 87.0. Average KT
      differences were 0.59 mm (allograft) and 0.34 mm (autograft group) (P = .58).
      IKDC activity scores were 2.9 (allografts) and 3.1 (autografts) postoperatively
      (P = .32). CONCLUSIONS: Using a patient-choice ACL graft selection program after
      appropriate counseling and using graft-specific rehabilitation programs, not
      chemically processed or irradiated BPTB allograft reconstructions have no greater
      failure rate than autografts in patients aged 25 years and younger at a minimum 2
      year follow-up. No significant differences in Cincinnati, Lysholm, and IKDC
      activity scores were found between these 2 groups. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 24680309
TI  - Outcomes after repair of chronic bucket-handle tears of medial meniscus.
AB  - PURPOSE: The purpose of this study was to determine the outcomes after repair of
      chronic bucket-handle medial meniscal tears by use of magnetic resonance imaging,
      clinical examination, and patient-reported outcomes. METHODS: A retrospective
      review of patients with chronic bucket-handle medial meniscal tears that had been
      repaired with meniscal sutures was undertaken. The following criteria for
      inclusion were adopted: minimum tear length of 2 cm and chronic medial meniscal
      tear identified at the time of arthroscopy. The tears were susceptible to
      dislocation with probing. Data collected included demographic, clinical,
      radiologic, and surgical data. Postoperative healing was assessed with the
      clinical criteria of Barrett et al. The International Knee Documentation
      Committee rating, Lysholm score, and Tegner activity level were determined, and
      postoperative magnetic resonance imaging was used to evaluate healing in
      accordance with the criteria of Henning et al. RESULTS: Twenty-four patients
      fulfilled the inclusion criteria. The mean time from injury to surgery was 10
      months (range, 2 to 60 months). Sixteen patients underwent anterior cruciate
      ligament reconstruction, 1 patient underwent posterior cruciate ligament
      reconstruction, and 6 patients underwent meniscus repair only. A median of 5
      sutures (range, 3 to 6 sutures) were used for repair. Four cases (all of which
      had undergone meniscus repair only) required revision. Complete healing was
      achieved in 83% of cases according to the criteria of Barrett et al. The mean
      follow-up time was 48 months (range, 24 to 112 months). An International Knee
      Documentation Committee rating of A or B was achieved in the 20 patients who did
      not require revision. The median Lysholm score was 95 (range, 92 to 100). The
      median Tegner activity level before injury was 7, and it remained unchanged after
      surgery in all cases. CONCLUSIONS: This study showed that repair of chronic
      bucket-handle meniscal tears can lead to good clinical outcomes and a relatively
      low (17%) failure rate. In addition, repairs of isolated meniscal tears had a
      significantly higher risk of failure than repairs performed in conjunction with
      anterior cruciate ligament reconstruction. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 24680310
TI  - Evidence-based status of osteochondral cylinder transfer techniques: a systematic
      review of level I and II studies.
AB  - PURPOSE: Our purpose was to examine the Level I and II evidence for the use of
      osteochondral cylinder transfer technique (OCT) for cartilage repair. METHODS: A
      literature search was carried out for Level I and II evidence studies on
      cartilage repair using the PubMed database. All the studies that involved OCT
      were identified. Only Level I and II studies that compared OCT to other
      modalities of treatment such as microfracture (MF) and autologous chondrocyte
      implantation (ACI) were selected. RESULTS: A total of 8 studies matched the
      selection criteria with 2 Level I and 6 Level II studies. Four studies compared
      OCT with MF, 3 compared OCT with ACI, and one compared all 3 techniques. Of 3
      studies, 4 came from a single center. Mean age of patients ranged from 24 to 33
      years, and mean follow-up ranged from 9 to 124 months. The studies from the
      single center showed superior results from OCT over MF, especially in younger
      patients, with one study having long-term follow-up of 10 years. They also showed
      an earlier return to sports. The size of the lesions were small (average < 3
      cm(2)). The 4 other independent studies did not show any difference between OCT
      and ACI, with one study showing inferior outcome in the OCT group. Magnetic
      resonance imaging (MRI) showed good osseous integration of the osteochondral
      plugs to the subchondral bone. Histologic examination showed that there was
      hyaline cartilage in the transplanted osteochondral plugs but no hyaline
      cartilage between the plugs. CONCLUSIONS: From the studies of a single center,
      OCT had an advantage over MF in younger patients with small chondral lesions.
      Comparison of outcomes between OCT and ACI showed no significant difference in 2
      studies and contrasting results in another 2 studies. There was insufficient
      evidence for long-term results for OCT. LEVEL OF EVIDENCE: Level II, systematic
      review of Level I and II studies.

PMID- 24680311
TI  - Management of primary acute anterior shoulder dislocation: systematic review and
      quantitative synthesis of the literature.
AB  - PURPOSE: The aim of this study was to compare the clinical outcome of surgical
      versus conservative treatment of primary acute anterior dislocation of the
      shoulder. METHODS: A systematic review of published studies on the treatment of
      primary acute anterior dislocation of the shoulder was performed. Three
      investigators independently conducted the research. A comprehensive search of
      PubMed, MEDLINE, CINAHL, Cochrane Library, EMBASE, and Google Scholar databases
      using various combinations of the keywords "shoulder," "dislocation,"
      "treatment," "acute," and "primary" over the years 1994 to 2013 was performed.
      The following data were extracted: demographics, soft tissue lesions and bone
      defects, outcome measurements, type of management, recurrence of instability, and
      complications. A quantitative synthesis of the literature was performed to
      compare surgery and conservative management and immobilization by internal and
      external in patients undergoing conservative treatment. RESULTS: Thirty-one
      studies were included in which 2,813 shoulders were evaluated. All patients
      sustained primary acute anterior shoulder dislocation. The mean Coleman
      Methodology Score (CMS) was 67 points (range, 19 to 84). Pooled results from
      comparative studies showed that the rate of recurrence was statistically
      significantly lower in the surgical group than in the conservative group (odds
      ratio, 12.71; 95% confidence interval [CI], 4.88 to 33.10; P < .00001). External
      rotation immobilization provided better results than internal rotation, being
      associated with a lower rate of recurrence (odds ratio, 2.28; 95% CI, 1.34 to
      3.87; P = .002). CONCLUSIONS: Although limited, the available evidence from
      randomized controlled trials (RCTS) supports primary surgery in young adults
      engaged in highly demanding sports or job activities. There is lack of evidence
      to determine whether surgical or nonsurgical treatment is better for other
      categories of injury. LEVEL OF EVIDENCE: Level IV, systematic review of Level I
      to IV studies.

PMID- 24680312
TI  - Trochleoplasty versus nontrochleoplasty procedures in treating patellar
      instability caused by severe trochlear dysplasia.
AB  - PURPOSE: The purpose of this study was to compare the clinical outcomes and
      postoperative complication rates between patients who underwent trochleoplasty or
      nontrochleoplasty procedures in treating patellar instability caused by severe
      trochlear dysplasia (STD). METHODS: The PubMed database was searched using
      specific inclusion and exclusion criteria for clinical studies reporting indexed
      orthopaedic treatments of patellar instability caused by STD (Dejour type B to
      D). Participants within studies were classified into one of the 2 treatment
      groups: (1) the trochleoplasty group (group T) and (2) the nontrochleoplasty
      group (group N). Clinical outcomes and postoperative complications were analyzed.
      RESULTS: Seventeen studies were finally included. There were in total 459 knees
      that underwent the indexed orthopaedic treatments of patellar instability caused
      by STD (Dejour type B to D). Eleven studies, including 329 knees, formed the
      trochleoplasty group (group T), and the remaining 6 studies, including 130 knees,
      composed the nontrochleoplasty group (group N). All the clinical outcomes within
      groups had improved significantly (P < .05) at the final follow-up. No studies
      directly compared the clinical outcomes between the 2 groups. The postoperative
      complication analysis showed superior results for the trochleoplasty group in (1)
      patellar redislocation rate and (2) percentage of patellofemoral osteoarthritis
      (Iwano grade 2 or greater) progression findings but an inferior outcome with
      respect to the range of motion (ROM) deficit compared with the nontrochleoplasty
      group. CONCLUSIONS: This systematic review showed significant postoperative
      improvements both in patients undergoing the trochleoplasty procedures and in
      patients undergoing the nontrochleoplasty procedures for the treatment of
      patellar instability caused by STD in all the included studies. However, there is
      limited evidence regarding the comparative advantages toward the optimal
      treatment. The postoperative complication rate has been considered to be the best
      measurement of operative success. To prevent the patella from redislocating and
      patellofemoral osteoarthritis from progressing, trochleoplasty procedures should
      be considered. Meanwhile, one should be cautious about the postoperative ROM
      deficit before choosing trochleoplasty procedures. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level III and IV studies.

PMID- 24680313
TI  - [Contribution of vascular ultrasonography in patients with ischemic strokes in
      Brazzaville (Congo)].
AB  - OBJECTIVE: To determine the prevalence of the carotid lesions during ischemic
      strokes. METHODS: This was a descriptive cross-sectional study, conducted in
      Brazzaville from January 2011 to June 2012 in a consecutive series of 73
      patients, victims of a transient ischemic attack or ischemic stroke, documented
      by a brain computed tomography. All patients underwent vascular ultrasonography
      of the supra-aortic trunks, carried out within the framework of etiological
      assessment. The examination searched for plaques, parietal infiltration
      (measurement of intima-media thickness), and carotid stenosis or occlusion.
      RESULTS: There were 49 men (67%) and 24 women (33%), mean age 58.7 +/- 11.8
      years. Eleven patients (15%) had a transient ischemic attack and 62 (85%) an
      ischemic stroke. The identified independent vascular risk factors were known and
      treated hypertension (n=66, 90.4%), dyslipidemia (n=16, 22%), diabetes mellitus
      (n=9, 12.3%), and smoking (n=5, 6.8%), with on average 2.5 factors per
      individual. Vascular ultrasonography of the supra-aortic trunks, normal in 44
      patients (60.3%) was pathological in the other 29 (39.7%). The main anomalies
      were atheromatous plaque (n=10, 13.7%), parietal infiltration (n=19, 26%). On
      average intima-media thickness was 0.86 +/- 0.11 mm on the left and 0.83 +/- 0.11
      mm on the right. Two cases of moderate stenosis were noted on the right and left
      internal carotids, respectively. CONCLUSION: This preliminary study confirms the
      existence of carotid atherosclerosis anomalies during ischemic strokes. These
      lesions, though non-significant, must nevertheless be taken into consideration
      when searching for the cause of stroke in high-risk vascular patients.

PMID- 24680315
TI  - What I cannot create, I do not understand: Comment on "Physical methods for
      genetic transformation of fungi and yeast" by Ana Leonor Rivera, Denis Magana
      Ortiz, Miguel Gomez-Lim, Francisco Fernandez and Achim M. Loske.

PMID- 24680314
TI  - Repeated inhalation exposure of rats to an anionic high molecular weight polymer
      aerosol: application of prediction models to better understand pulmonary effects
      and modes of action.
AB  - Opposed to the wealth of information available for kinetic lung overload-related
      effects of poorly-soluble, low-toxicity particles (PSP), only limited information
      is available on biodegradable high molecular weight (HMW) organic polymers
      (molecular weight >20,000 Da). It is hypothesized that such types of polymers may
      exert a somewhat similar volume displacement-related mode of action in alveolar
      macrophages as PSP; however, with a differing biokinetics of the material
      retained in the lung. This polyurethane polymer was examined in single and 2-/13
      week repeated exposure rat inhalation bioassays. The design of studies was
      adapted to that commonly applied for PSP. Rats were nose-only exposed for 6h/day
      for the respective study duration, followed by 1-, 2- and 4-week postexposure
      periods in the single, 2- and 13-week studies, respectively. While the findings
      in bronchoalveolar lavage (BAL) and histopathology were consistent with those
      typical of PSP, they appear to be superimposed by pulmonary phospholipidosis and
      a much faster reversibility of pulmonary inflammation. Kinetic modeling designed
      to estimate the accumulated lung burden of biopersistent PSP was also suitable to
      simulate the overload-dependent outcomes of this biodegradable polymer as long as
      the faster than normal elimination kinetics was observed and an additional 'void
      space volume' was added to adjust for the phagocytosed additional fraction of
      pulmonary phospholipids. The changes observed following repeated inhalation
      exposure appear to be consistent with a retention-related etiopathology (kinetic
      overload). In summary, this study did not reveal evidence of any polymer-specific
      pulmonary irritation or parenchymal injury. Taking all findings into account, 7
      mg polymer/m(3) (exposure 6h/day, 5-days/week on 13 consecutive weeks)
      constitutes the point of departure for lower respiratory tract findings that
      represent a transitional state from effects attributable to an overload-dependent
      pulmonary inflammation and phospholipidosis. In regard to extrapulmonary
      toxicity, no effects were found up to the maximum concentration of 107 mg/m(3)
      examined.

PMID- 24680316
TI  - Is ictal cognitive dysfunction predictable?
AB  - OBJECTIVE: Accurate prediction of electrographic seizure onset may reduce
      injuries and improve quality of life in pharmaco-resistant epileptics. However,
      because sub-clinical, far out-number clinical seizures, indiscriminate issuance
      of warnings may have a paralyzing effect on these patients. This study
      investigates the predictability of ictal cognitive dysfunction. METHODS: Latency
      and percentage of correct responses to a reaction time test triggered by
      automated seizure detections were compared to those obtained inter-ictally in 14
      subjects undergoing surgery evaluation. Since accurate prediction of seizures is
      elusive, early detection was used, as it indirectly but reliably investigates for
      the existence of a cognitive pre-ictal state. RESULTS: Significant differences
      between ictal and inter-ictal cognitive performance were not uncovered until late
      into the temporal evolution of "focal" seizures. CONCLUSIONS: These observations
      suggest that cognitive dysfunction is unpredictable in seizures originating from
      discrete cortical regions, as the transition into unawareness seems abrupt.
      SIGNIFICANCE: Prediction of electrographic seizure onsets with worthwhile
      accuracy would likely result in large numbers of daily warnings, the great
      majority for sub-clinical seizures. This outcome would considerably increase,
      without safety justification, patients' psychological burden inherent to each
      forecast, thus further diminishing quality of life.

PMID- 24680317
TI  - Vestibular function and vestibular evoked myogenic potentials (VEMPs) in
      spasticity.

PMID- 24680318
TI  - Predicting the unpredictable: the challenge or mirage of seizure prediction?

PMID- 24680319
TI  - Eccentric femoral tunnel widening in anatomic anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate femoral tunnel
      widening (TW) and migration of the femoral tunnel aperture after anatomic
      anterior cruciate ligament (ACL) reconstructions with hamstring grafts and bone
      patellar tendon-bone (BPTB) grafts. METHODS: Of the 105 consecutive patients who
      underwent ACL reconstruction, the 52 patients who underwent isolated ACL
      reconstruction and in whom tunnel measurement could be obtained by computed
      tomography were included in this study. In 26 patients, double-bundle
      reconstruction (DBR) of the ACL using hamstring tendons was performed. These
      patients were compared with 26 patients in whom rectangular tunnel ACL
      reconstruction using BPTB grafts (BPTBR) was performed. Femoral tunnel aperture
      positioning and TW were investigated postoperatively using 3-dimensional computed
      tomographic images, which were performed a week and a year after surgery in all
      patients. RESULTS: In DBR, the average diameter of the anteromedial (AM) femoral
      tunnel increased by 34.0% in the horizontal direction and 28.2% in the vertical
      direction, whereas that of the posterolateral (PL) femoral tunnel increased by
      58.2% and 73.4%, respectively, at 1 year after surgery compared with 1 week after
      surgery. The percentage TW value of the PL tunnel was significantly greater than
      that of the AM tunnel. In BPTBR, the average diameter increased by 22.0% and
      17.1%, respectively. The percentage TW value of the PL tunnel in DBR was
      significantly greater than that of the femoral tunnel in BPTBR. Each tunnel
      aperture migrated distally ("shallow") in the horizontal direction and high in
      the vertical direction. AM and PL tunnel apertures in DBR migrated in the
      vertical direction significantly more than they did in BPTBR. No significant
      differences between the 2 groups were found in clinical outcomes. CONCLUSIONS:
      The femoral PL tunnel aperture in DBR showed significantly more widening than did
      the AM tunnel aperture in DBR and the femoral tunnel aperture in BPTBR. Also,
      greater migration of the femoral tunnel aperture in the vertical direction
      because of TW was observed in DBR than in BPTBR. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 24680320
TI  - Arthroscopic irrigation and debridement in the treatment of septic arthritis
      after anterior cruciate ligament reconstruction.
AB  - PURPOSE: To systematically review the literature and characterize the success and
      failure rates of arthroscopic irrigation and debridement (I & D) in the treatment
      of septic arthritis after anterior cruciate ligament (ACL) reconstructions. We
      also aimed to identify which variables affected the failure rate. METHODS: Five
      databases (MEDLINE, Ovid, Medscape, Web of Science, and Google Scholar) were
      screened for clinical studies involving the treatment of septic arthritis after
      ACL reconstruction with arthroscopic I & D. A full-text review of eligible
      studies was conducted. Inclusion and exclusion criteria were applied to the
      searched studies. Failure of I & D was defined as the need for graft removal or
      revision ACL reconstructive surgery because of infection. Data from the selected
      studies were combined for statistical analyses to elucidate factors associated
      with the success or failure. RESULTS: We identified 11 eligible studies involving
      90 patients. These studies described the results of 90 arthroscopic I & D
      procedures with an overall success rate of 85.6%. Repeated I & D was necessary in
      34.5% of patients. Removal of the graft with or without subsequent revision ACL
      reconstruction was reported in 13 (14.4%) cases. Statistical analysis showed that
      cases involving Staphylococcus aureus (P = .053), 2 or more I & D procedures (P =
      .029), and allografts (P < .0001) were at greater risk of failure. CONCLUSIONS:
      Arthroscopic I & D with graft retention is an effective treatment for patients
      with septic arthritis after ACL reconstruction. Factors affecting the failure
      rate may include graft choice and organism virulence. LEVEL OF EVIDENCE: Level
      IV, systematic review of Level IV studies.

PMID- 24680321
TI  - Arthroscopic repair of lateral ankle ligament complex by suture anchor.
AB  - PURPOSE: Arthroscopic repair of the lateral ligament complex with suture anchors
      is increasingly used to treat chronic ankle instability (CAI). Our aims are (1)
      to analyze and evaluate the literature on arthroscopic suture anchor repair of
      the anterior talofibular ligament and (2) to conduct a systematic review of the
      clinical evidence on the reported outcomes and complications of treating CAI with
      this technique. METHODS: We performed a systematic review of the literature using
      PubMed, Ovid, Elsevier ScienceDirect, Web of Science-Conference Proceedings
      Citation Index, and the Cochrane Database of Systematic Reviews from 1987 to
      September 2013. Clinical studies using the arthroscopic suture anchor technique
      to treat CAI were included. Outcome measures consisted of clinical assessment of
      postoperative ligament stability and complications. In addition, the methodologic
      quality of the included studies was assessed by use of the modified Coleman
      Methodology Score. RESULTS: After reviewing 371 studies, we identified 6 studies
      (5 retrospective case series and 1 prospective case series, all Level IV) that
      met the inclusion criteria, with a mean Coleman Methodology Score of 71.8 +/-
      7.52 (range, 63 to 82). In these studies 178 patients (179 ankles) underwent
      arthroscopic suture anchor repair of the anterior talofibular ligament with a
      mean follow-up period of 38.9 months (range, 6 to 117.6 months). All patients
      were reported to have subjective improvement of their ankle instability, with
      complications in 31 cases. CONCLUSIONS: Studies of arthroscopic suture anchor
      technique to treat CAI are sparse, with moderate mean methodologic quality. The
      included studies suggest that the arthroscopic technique is a feasible procedure
      to restore ankle stability; however, on the basis of our review, this technique
      seems to be associated with a relatively high complication rate. Extensive
      cadaveric studies, clinical trials, and comparative studies comparing
      arthroscopic and open repair should be performed in the future. LEVEL OF
      EVIDENCE: Level IV, systematic review of Level IV studies.

PMID- 24680322
TI  - Clinical results after arthroscopic treatment for septic arthritis of the elbow
      joint.
AB  - PURPOSE: The purpose of this study was to examine clinical findings of septic
      arthritis of the elbow joint in a series of immunocompetent patients and to
      evaluate the outcomes after arthroscopic treatment. METHODS: Between October 2006
      and January 2012, 11 patients with septic arthritis of the elbow underwent
      arthroscopic surgery. History, laboratory findings, and radiologic findings were
      reviewed. Functional outcomes were evaluated using the Mayo Elbow Performance
      Score (MEPS). RESULTS: The study included 5 men and 6 women with a mean age of 45
      years. An underlying medical disease was present in 1 patient (diabetes).
      Staphylococcus aureus was the most common organism identified (5 patients). There
      was 1 reoperation and no complications related to the arthroscopic procedure.
      Eight of 11 patients had excellent results assessed by MEPS at the final follow
      up. The mean MEPS was 94.5 at the final follow-up. CONCLUSIONS: Septic arthritis
      of the elbow joint can occur in otherwise healthy patients without pre-existing
      elbow disease. Arthroscopic irrigation and synovectomy are safe and effective in
      patients with septic arthritis and result in good functional outcomes. LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 24680323
TI  - Confirming a prediction of the calcium hypothesis of photoreceptor aging in mice.
AB  - Prior work in healthy rats supported a calcium hypothesis of photoreceptor aging,
      wherein progressive age-related declines in photopic vision are explainable by
      the extent of earlier escalating d-cis-diltiazem-insensitive increases in
      photoreceptor L-type calcium channel (LTCC) activity in vivo. Unlike rats,
      healthy mice have relatively stable photopic vision until after 18 months of age.
      We therefore hypothesized that photoreceptor LTCC activity in mice would not
      progressively increase until after 18 months. In 2-5, 10, 18, and 26 months male
      C57Bl/6J mice, photoreceptor LTCC activity and retinal thickness were evaluated
      in vivo (manganese-enhanced magnetic resonance imaging) with some groups also
      treated with d-cis-diltiazem; visual performance was evaluated (optokinetic
      tracking). Data were calibrated for cone-only responses using mice without rod
      transducin (GNAT1-/-). Photopic vision was stable until after 18 months without
      retinal thinning or progressive increases in retinal manganese uptake. We
      measured an uptake spike at 10 months. This spike, unlike that in the rat, was
      diltiazem sensitive in the dark and diltiazem insensitive in the light. Between
      dark and light, uptake in inner retina of older mice was unequal (unlike that in
      2-5 months mice); outer retinal uptake was similar to that in 2-5 months mice.
      Stable murine photopic visual performance and nonescalating photoreceptor LTCC
      activity before 18 months of age were consistent with a prediction of the calcium
      hypothesis. Stark differences in the temporal evolution of mouse and rat
      photoreceptor LTCC activity suggest the need for personalized identification of
      the retinal mechanisms contributing to declines in photopic vision to ensure
      success of future treatment efforts. 

PMID- 24680324
TI  - Plasma oxidized low-density lipoprotein levels and risk of Alzheimer's disease.
AB  - This study examines the association of plasma oxidized low-density lipoprotein
      (OxLDL) levels with all-cause dementia, including Alzheimer's disease (AD) and
      vascular dementia. Data are taken from the Canadian Study of Health and Aging, a
      population-based study of a representative sample of persons aged more than 65
      years conducted from 1991 to 2002. The present study sample included 670 subjects
      of which, 155 developed all-cause dementia with 109 cases of AD and 32 of
      vascular dementia. In Cox regression models, no association between OxLDL and
      risks of dementia or subtypes was found. A triple interaction between OxLDL, sex,
      and history of cardiovascular disease on the risk of AD (p = 0.0077) was found.
      Increased levels of OxLDL were significantly associated with an increased risk of
      AD in men with a history of cardiovascular disease (hazard ratio = 1.11; 95%
      confidence interval 1.04-1.19); no association in women was found. These findings
      suggest that increased levels of OxLDL are not associated with the risk of
      dementia, AD, and vascular dementia. The association of OxLDL with AD in men with
      a history of cardiovascular disease merits further investigation. 

PMID- 24680325
TI  - Aging increases the susceptibility to motor memory interference and reduces off
      line gains in motor skill learning.
AB  - Declines in the ability to learn motor skills in older adults are commonly
      attributed to deficits in the encoding of sensorimotor information during motor
      practice. We investigated whether aging also impairs motor memory consolidation
      by assessing the susceptibility to memory interference and off-line gains in
      motor skill learning after practice in children, young, and older adults.
      Subjects performed a ballistic task (A) followed by an accuracy-tracking task (B)
      designed to disrupt the consolidation of A. Retention tests of A were performed
      immediately and 24 hours after B. Older adults showed greater susceptibility to
      memory interference and no off-line gains in motor skill learning. Performing B
      produced memory interference and reduced off-line gains only in the older group.
      However, older adults also showed deficits in memory consolidation independent of
      the interfering effects of B. Age-related declines in motor skill learning are
      not produced exclusively by deficits in the encoding of sensorimotor information
      during practice. Aging also increases the susceptibility to memory interference
      and reduces off-line gains in motor skill learning after practice. 

PMID- 24680327
TI  - [To grasp the opportunity for development and to improve the quality of the
      journal].

PMID- 24680328
TI  - [Inheritance and development of otorhinolaryngology head and neck surgery in
      China].

PMID- 24680326
TI  - Accelerated white matter aging in schizophrenia: role of white matter blood
      perfusion.
AB  - Elevated rate of age-related decline in white matter integrity, indexed by
      fractional anisotropy (FA) from diffusion tensor imaging, was reported in
      patients with schizophrenia. Its etiology is unknown. We hypothesized that a
      decline of blood perfusion to the white matter may underlie the accelerated age
      related reduction in FA in schizophrenia. Resting white matter perfusion and FA
      were collected using pseudo-continuous arterial spin labeling and high-angular
      resolution diffusion tensor imaging, respectively, in 50 schizophrenia patients
      and 70 controls (age = 18-63 years). Main outcome measures were the diagnosis-by
      age interaction on whole-brain white matter perfusion, and FA. Significant age
      related decline in brain white matter perfusion and FA were present in both
      groups. Age-by-diagnosis interaction was significant for FA (p < 0.001) but not
      white matter perfusion. Age-by-diagnosis interaction for FA values remained
      significant even after accounting for age-related decline in perfusion.
      Therefore, we replicated the finding of an increased rate of age-related white
      matter FA decline in schizophrenia and observed a significant age-related decline
      in white matter blood perfusion, although the latter did not contribute to the
      accelerated age-related decline in FA. The results suggest that factors other
      than reduced perfusion account for the accelerated age-related decline in white
      matter integrity in schizophrenia.

PMID- 24680329
TI  - [Unmet needs in rhinological research in China].

PMID- 24680330
TI  - [Topical injection and systemic application of glucocorticoids in the treatment
      of idiopathic sudden sensorineural hearing loss by type].
AB  - OBJECTIVE: To investigate the therapeutic effect of topical corticosteroids
      injection and systemic application in the treatment of typing idiopathic sudden
      sensorineural hearing loss (ISSNHL). METHODS: Total of 438 patients with ISSNHL,
      including 76 with hearing loss in low-middle frequencies, 43 in middle-high
      frequencies, 162 in all frequencies and 157 in total deafness, were randomly
      divided into two groups, the systemic application group: dexamethasone (DEX) was
      applied by intravenous injection in dose of 10 mg*3 d followed by 5 mg*4 d, and
      the topical injection group: methylprednisolone sodium succinate of 40 mg was
      injected into cortical bone of mastoid region every three days. According to the
      results of pure-tone threshold audiometry, the curative effect among ISSNHL with
      low-middle frequencies, middle-high frequencies, all frequencies hearing loss,
      and total deafness were evaluated. SPSS 18.0 software was used to analyze the
      data. RESULTS: Among 220 patients with systemic application of DEX, 66 subjects
      (30.0%) cases were recovery, 51 (23.2%) were excellent better, 39 (17.7%) better,
      64 (29.1%) were poor, and the total effective rate was 70.9% (156/220) . There
      was no statistical difference in total effective rate of four typing subgroups
      (chi(2) = 1.60, P > 0.05). And the recovery rate in total deafness subgroup was
      significant lower than that in low-middle and all frequencies subgroups (chi(2) =
      10.63 and 15.94 respectively, both P < 0.05). In the topical injection group, the
      recovery rate was 30.3% (66 cases), excellent better 18.8% (41), better 15.6%
      (34), poor 35.3% (77), and the total effective rate was 64.7% (141/220) . There
      were statistical differences of total effective rate in low-middle frequencies in
      comparison with that in all frequencies (chi(2) = 8.38) and total deafness
      (chi(2) = 7.28) subgroups (both P < 0.05). Regarding recovery rate, there were
      significant differences between each two typing subgroups, except middle-high
      frequencies subgroup vs. all frequencies (chi(2) = 1.60) and total deafness
      (chi(2) = 2.29) subgroups (both P < 0.05). In 76 ISSNHL with hearing loss in low
      middle frequencies, the recovery rate in cases with local corticosteroids
      injection(65.0%) was significantly increased in comparison with that with
      systemic application (41.7%), chi(2) = 4.15, P < 0.05. There were increasing
      tendencies of curative effect in other three typing groups by systemic
      corticosteroids application when compared with local injection, but no
      statistical significances (all P > 0.05). CONCLUSIONS: For low-middle frequencies
      ISSNHL, the corticosteroids administration of local injection should be the
      optimization. Systemic application would be applied for middle-high frequencies,
      all frequencies and total deafness.

PMID- 24680331
TI  - [Transsphenoidal endoscopic endonasal approach for the surgery of pituitary
      abscess].
AB  - OBJECTIVE: To evaluate the effectiveness of transsphenoidal endoscopic endonasal
      approach for the surgery of pituitary abscess. METHODS: Eighteen pathologically
      diagnosed pituitary abscess were resected through transsphenoidal endoscopic
      endonasal approach at Tianjing Huanhu hospital between January 2000 and December
      2011.Retrospective analysis was done upon clinical presentations and imaging
      features. There were 6 males and 12 females. The average age was 48.5 years old
      and the average disease course was 5.8 years. The typical clinical manifestations
      included headache (13 cases), pituitary dysfunction (10 cases), Diabetes
      Insipidus (4 cases) visual interference (8 cases) and fever (4 cases). All cases
      were resected by transsphenoidal endoscopic endonasal approach with general
      anesthesia. The postoperative symptoms and follow-up results were recorded.
      RESULTS: All patients were followed up from 6 months to 6 years. Postoperatively,
      headache was recovered in 13 cases, visual was improved in 6 cases,
      hypopituitarism was relieved in 8 cases and polyuria was disappeared in 3 cases.
      One case was recurrent and cured by transsphenoidal endoscopic endonasal
      approach. CONCLUSIONS: Transsphenoidal endoscopic endonasal approach for the
      surgery of pituitary abscess is effective.

PMID- 24680332
TI  - [Development of the Chinese nasal obstruction symptom evaluation (NOSE)
      questionnaire].
AB  - OBJECTIVE: To develop the Chinese version of the nasal obstruction symptom
      evaluation (NOSE) questionnaire. METHODS: After introduction, forward and
      backward translation, synthesis, expert committee review, pretest, adaptation and
      validation followed the international guidelines, the Chinese version of NOSE
      scale was tested among 223 nasal septal deviation patients and 80 health
      volunteers to further assess its psychometric and clinical properties. SPSS 19.0
      software was used to analyze the data. RESULTS: The Chinese version demonstrated
      satisfactory evaluation results. The acceptance rate of the questionnaire was
      97.6% and 94.1% in the patient group and control group respectively, and the
      completion time was (1.5 +/- 0.5)min and (1.0 +/- 0.5)min. Internal consistency
      reliability (Cronbach's alpha) was calculated to be 0.869. Test-retest
      reliability coefficient was adequate at rs = 0.996. Content validity was approved
      by our expert committee. Criteria validity (Spearman correlation coefficient)
      between NOSE Chinese version and SF-36, as well as VAS was -0.837 and 0.725
      separately. Construct validity of Chinese version was similar to that of the
      original edition. The standardized response mean and the effect size at three
      months postoperatively was respectively 1.34 and 1.21, indicating high
      responsiveness. Calculated by Mann-Whitney U test, the instrument showed
      excellent sensitivity to discriminate the subjects with or without nasal
      obstruction (P < 0.01). The NOSE scores were also correlated with nasal
      resistance by rhinomanometry. CONCLUSIONS: The NOSE Chinese version was
      successfully cross-cultural adapted and validated. It therefore can be
      recommended as a robust tool for future measuring subjective severity of nasal
      obstruction in China.

PMID- 24680333
TI  - [Preliminary study of patterns of level IIb lymph node metastasis in papillary
      thyroid carcinoma].
AB  - OBJECTIVE: To evaluate the factors related to level IIb lymph node(LN) metastasis
      in papillary thyroid carcinoma (PTC). Method The medical records of 63 PTC
      patients were reviewed. The patients underwent neck dissection (ND) between
      January 2011 and December 2012, who were determined with pathologically lateral
      cervical LN metastasis. A total of 67 ND specimens were obtained and analyzed for
      LN involvement with respect to neck levels. The relation of level IIb LN
      metastasis with clinical factors, including age and sex of patients, tumor size,
      location, multifocality, extracapsular spread (ECS) and stage of primary PTC,
      coexistence of lymphocytic thyroiditis, distribution of metastasis LN in
      different levels, fusion and extracapsular invasion of LN were analyzed with
      univariate analysis and chi(2) test. SPSS 14.0 software was used to analyze the
      data. RESULTS: Of 63 patients, 41 patients revealed thyroid tumor maximum
      diameter more than 1 centimeter, 26 patients with tumor located in the upper 1/3
      thyroid lobe, 39 patients with multiplicity of thyroid tumor and 54 patients with
      ECS, 54 patients with pathological T3/T4a stage, 15 patients with coexisting
      lymphocytic thyroiditis. Among the 67 ND specimens, 12 specimens (17.9%) showed
      level IIb LN metastasis and the incidences of LN metastasis at level IIa, III,
      IV, V, VI, IIa+III, III+IV, and IIa+III+IV were 56.7%, 86.6%, 68.7%, 22.4%,
      86.6%, 52.2%, 55.2%, 37.3%, respectively. Of the 38 ND specimens with level IIa
      LN metastases, 10 were positive in level IIb(26.3%). But of 29 ND specimens
      without level IIa LN metastases, only 2 were positive in level IIb. A univariate
      analysis revealed that level IIa LN metastasis was a significant predictive
      factor for level IIb LN metastasis (chi(2) = 4.219, P = 0.040). CONCLUSION: The
      incidence of LN metastasis to level IIb is low in PTC, which is less when level
      IIa is not involved.

PMID- 24680334
TI  - [Surgical treatment for cervicothoracic esophageal carcinoma with tracheal
      involvement].
AB  - OBJECTIVE: To evaluate the surgical treatment and outcome of cervicothoracic
      esophageal carcinoma with tracheal. METHODS: Ten cases of cervicothoracic
      esophageal carcinoma with tracheal invasion underwent surgical treatment between
      2004 and 2011 was reviewed. Operative methods, complications, pathology, and
      prognosis were analyzed. RESULTS: The patients were divided into 2 groups, 5
      patients with cervical tracheal invasion group and 5 patients with
      cervicothoracic tracheal invasion. Thoracotomy and anterior mediastinal
      tracheostomy (AMT) were required for 5 patients with cervicothoracic tracheal
      invasion. The median follow-up was 23 months (ranging from 6 to 76 months). Of 5
      patients with cervical tracheal invasion, 3 patients survived with free of
      disease for more than 5 years postoperatively, 1 patient died of local recurrence
      at 14 months postoperatively, and 1 patient died of cardiac infarction at 26
      months postoperatively. Among 5 patients with cervicothoracic tracheal invasion,
      2 patients died during hospitalization, and 1 patient died of local recurrence at
      16 months postoperatively, and 2 patients died of distant metastasis at 6 and 20
      months after surgery respectively. CONCLUSIONS: Tracheal invasion is not a
      contraindication to radical operation for the cervicothoracic esophageal
      carcinoma. Surgical treatment has a good outcome in cervicothoracic esophageal
      carcinoma with only cervical tracheal invasion. If thoracic trachea is involved,
      especially when the length of the distal trachea is less than 5 cm, operation
      should be performed with caution.

PMID- 24680335
TI  - [Clinical features of inflammatory myofibroblastic tumor in the head and neck].
AB  - OBJECTIVE: To summarize the clinical characteristics of inflammatory
      myofibroblastic tumor (IMT) in head and neck and to discuss its treatment.
      METHODS: Twenty-seven cases of IMT in head and neck diagnosed at the Chinese PLA
      General Hospital from 2004 to 2012 were analyzed retrospectively. Among the 27
      patients, 12 males and 15 females, age ranged from 8 to 77 years, with a median
      43 years old. Treatment included: 1 with radiotherapy, 22 with surgery, 3 with
      surgery and postoperative radiotherapy, one with concurrent chemoradiotherapy
      followed by surgery. Of the 27 cases, 5 located in the neck, 6 in the nasal and
      paranasal sinus, 4 in the temporal bone, 3 in the throat, 2 in the parotid gland,
      2 in the lower pharynx, 1 in the mandible, 1 in the maxilla, 1 in the masseter
      muscle, 1 in the amygdala and 1 in the pharynx nasalis. RESULTS: Following-up
      time was 4-85 months, with a median of 26 months. Six cases lost follow-up, 1
      case with malignant transformation and died, 16 cases survived with no
      recurrence, 4 cases relapsed, of whom 2 were alive with tumors and 2 died.
      CONCLUSIONS: IMT in the head and neck has a tendency to be malignancy, with
      certain recurrence rate and mortality. Radical excision is still the first choice
      of treatment for IMT in head and neck.

PMID- 24680336
TI  - [Identification of cervical lymph node micrometastasis of tongue cancer by color
      Doppler and MRI].
AB  - OBJECTIVE: To assess the values of color Doppler and magnetic resonance imaging
      (MRI) in the identification of cervical lymph node micrometastasis of tongue
      cancer. METHODS: Totally 96 cases of tongue cancer with impalpable neck lymph
      node was examined with color Doppler and MRI within one week before surgery. Chi
      square test was used to assess if the presence of regional lymph node
      micrometastasis, histopathological analysis as a golden standard lymph node
      micrometastasis. RESULTS: For the diagnosis of cervical lymph node
      micrometastasis, color Doppler was significantly better than MRI in sensitivity
      (72.5% vs 50.0%, P = 0.039) and the accuracy (78.1% vs 64.6%, P = 0.038), but no
      significant difference in the specificity (82.1% vs 75.0%, P = 0.357), the
      positive predictive value (74.4% vs 58.8%, P = 0.159) and the negative predictive
      value (80.7% vs 67.7%, P = 0.108). CONCLUSION: Color Doppler is better than MRI
      in the sensitivity and accuracy for the diagnosis of cervical lymph node
      micrometastasis of tongue cancer.

PMID- 24680337
TI  - [Relationship between plasma vascular endothelial growth factor and tumor
      necrosis factor-alpha and obstructive sleep apnea hypopnea syndrome in children].
AB  - OBJECTIVE: To investigate the relation of plasma vascular endothelial growth
      factor(VEGF) and tumor necrosis factor-alpha (TNF-alpha) with obstructive sleep
      apnea-hypopnea syndrome(OSAHS) in children. METHODS: Eighty children were
      recruited from October 2008 to March 2009, including 60 children with snoring and
      20 healthy children without snoring as control. Plasma VEGF or TNF-alpha
      concentration was measured by enzyme-linked immunosorbent assay (ELISA)
      respectively. Sixty children with snoring underwent an overnight polysomnography
      test their PSG data, including whole night mean saturation (MSaO2), lowest oxygen
      saturation (LSaO2), desaturation cumulate time/total sleep time (DCT/TST), oxygen
      desaturation index 3 (ODI3), apnea-hypopnea index (AHI), obstructive apnea index
      (OAI), were collected and analysed. SPSS 13.0 software was used to analyze the
      data. RESULTS: The levels of plasma VEGF and TNF-alpha in children with
      OSAHS(540.45 pg/ml and 311.94 pg/ml) were higher than those in children with
      snoring alone (234.45 pg/ml and 97.55 pg/ml) or those in healthy children (259.80
      pg/ml and 120.70 pg/ml), with statistically significant differences(HC
      value:14.176 and 15.571, P < 0.05, respectively), but with no statistical
      difference between children with snoring alone and healthy children (P > 0.05).
      The differences in plasma VEGF or TNF-alpha levels between children with moderate
      and severe hypoxemia and children with mild hypoxemia were not statistically
      significant (P > 0.05). Spearman rank correlation analysis showed no significant
      correlation between plasma level of VEGF or TNF-alpha and LSaO2, MSaO2, ODI3,
      DCT/TST, OAI, AHI or BMI (r values were <0.5, P > 0.05). CONCLUSION: Plasma
      levels of VEGF and TNF-alpha increase in children with OSAHS.

PMID- 24680338
TI  - [Culture of human nasal polyp epithelial cells at an air-liquid surface].
AB  - OBJECTIVE: To study the human nasal ciliated epithelial cells at an air-liquid
      surface (ALI) so as to establish a reliable cell culture model for nasal
      mucociliary transport study. METHODS: The human nasal ciliated epithelial cells
      were cultured by low-temperature enzymatic digestion method at an air-liquid
      surface, the cell growth behavior was observed under the inverted phase-contrast
      microscope, the proliferation, confluence and differentiation of cultured cells
      were examined by scanning electron microscope and immunocytochemistry, the basal
      and stimulated ciliary beat frequency (CBF) of cultured epithelial cells were
      measured by using high-speed digital microscopic imaging system. Prism 4.0
      software was used to analyze the data. RESULTS: (1) Under microscope, the cells
      on transwell membrane adhered well at 24 h and locked tightly to display with a
      cobblestone-like appearance; the monolayer cells got confluence to 80%-90% after
      one-week submersion culture, and thereafter exposed to air-liquid interface. (2)
      Under scanning electron microscope, the cilia and also the small microvilli could
      be observed to protrude from the cell's surface at ALI day 7; the ciliated cells
      differentiated well and distributed in cluster; goblet cells and nonciliated
      columnar cells distributed between ciliated cells. (3) Immunocytochemistry of
      beta-tubulin IV and zona occludens-1 showed a good confluence and differentiation
      of cilia in cultured epithelial cells at ALI day 14, and the percentage of
      ciliated epithelial cells was 50%-60 %. (4) The basal CBF of cultured epithelial
      cells was (8.42 +/- 1.24), (8.71 +/- 1.11), (9.17 +/- 1.11), (8.89 +/- 0.91),
      (8.99 +/- 0.91) Hz at ALI day 7, 14 , 21, 28, 35, respectively, no significant
      difference was found among them(F = 1.451, P > 0.05). (5) At the concentration of
      100 umol/L ATP, an exogenous stimulating agent, significantly increased the CBF
      of cultured epithelial cells. CONCLUSIONS: Air-liquid interface cultured human
      nasal epithelial cells by enzymatic digestion method manifest with good
      confluence and differentiation status; the cells could maintain differentiated
      morphology and physiological function close to in vivo epithelium for a long
      term, therefore, it may serve as an ideal cell model for mucociliary transport
      study.

PMID- 24680339
TI  - [Endoscopic transnasal approach for nasopharyngeal angiofibroma without arterial
      embolism].
AB  - OBJECTIVE: To explore the feasibility of endoscopic resection without arterial
      embolism for nasopharyngeal angiofibroma and the strategy of decreasing the
      bleeding during the operation. METHODS: The clinical data of twenty-five cases of
      nasopharyngeal angiofibroma were retrospective analyzed, including 3 cases of
      Radowski stageIIa, 5 cases of stageIIb, 4 cases of stageIIc and with 13 cases of
      stage IIIa. All cases did not receive the arterial embolism, and controlled
      hypotension were adopted under endoscopic transnasal approach during the tumor
      resection. Two cases were added the labiogingival incision. During the operation,
      under the opening vision, cutting out the outside of the infratemporal fossa, and
      the pterygoid process to adequate exposure the pterygopalatine fossa and
      infratemporal fossa.Early recognition of anatomical landmarks and establish the
      safety plane, along the periphery of the tumor to proceed with micro-separation,
      early blocking tumor nutrient vessels, en bloc resection of the tumor and some
      other ways to reduce bleeding and tumor resection. RESULTS: Amount of bleeding
      during operation was 600-1500 ml, none of them had internal carotid artery injury
      and intracranial injury or some other complication.Follow-up 2-3 years was
      available in all patients, except 1 case with residual of tumor surrounding the
      optic nerve, the other 24 cases had no residual tumor and relapses. CONCLUSIONS:
      The preoperative occlusion and artery ligation may not be needed.Surgical
      technique is the key to reduce blood loss, and it is feasible to have endoscopic
      resection of nasopharyngeal angiofibroma with proper operating technique.

PMID- 24680340
TI  - [Research on the patterns of upper airway obstructive levels by drug-induced
      sleep endoscopy].
AB  - OBJECTIVE: To identify the patterns of airway collapse in patients with
      obstructive sleep apnea hypopnea syndrome(OSAHS) by dexmedetomidine induced sleep
      endoscopy. METHODS: Forty-five obstructive sleep apnea patients diagnosed by
      polysomnography were given dexmedetomidine intravenously. Once the patient was
      sedated in dorsal position, the electronic nasopharyngoscope was inserted
      transnasally and positioned on five levels of the upper airway sequentially
      (velum, oropharyngeal lateral wall, tongue base, epiglottis and larynx) to
      observe and document the collapse. Each level should be observed no less than
      three apneas. The degree of airway narrowing was calculated by using the
      ImageTool. No obstruction was defined when the degree of airway narrowing <50%,
      and complete obstruction when >= 75%. RESULTS: In 45 patients with OSAHS, 1 case
      showed no obstruction on any level, 6 cases demonstrated obstructions on single
      level only, and 38 cases demonstrated complete obstructions on multilevel,
      including 17 cases with complete obstructions on two levels, 15 cases complete
      obstructions on three levels, and 6 cases complete obstructions on four levels.
      The patterns of collapse found in the trial were: (1) circumferential stricture
      by velum collapse was found in 43 patients, and 41 cases showed complete
      obstructions; (2) the side wall of oropharynx all collapsed in a lateral
      configuration, and 32 cases showed complete obstructions on this level; (3)
      anteroposterior swallowing tongue base was common, 11 cases showed partial
      obstructions on level of tongue base, and 10 cases complete; (4) epiglottic
      collapses occurred in lateral configuration folding as V shape; in
      anteroposterior configuration, epiglottis met posterior wall of the pharynx due
      to swallowing tongue base; the server soften epiglottis obstructed the entrance
      of the larynx, while the mild soften epiglottis and the collapsed side wall of
      pharynx came into being obstructions in concentric configuration; (5) the
      arytenoid area and aryepiglottic fold mucosa inwardly covered the glottis when
      the obstruction occurred in the larynx. CONCLUSIONS: The patterns of hypopharynx
      obstructions in OSAHS patients are multifarious. Lateral oropharyngeal wall,
      epiglottic and tone base collapse play an important role in the obstructions. The
      laryngeal obstruction can also be observed.

PMID- 24680341
TI  - [Epidural hematoma after cochlear implantation: a case report].

PMID- 24680342
TI  - [Endoscopic treatment using ethmoidal artery as pedicle of the septum flap repair
      for iatrogenic meningeal encephalocele with cerebrospinal fluid leak: a case
      report].

PMID- 24680343
TI  - [Live leech tracheobronchial foreign bodies in 2 rural children].

PMID- 24680344
TI  - [Removal of fibrolipoma in orbital and ethmoid sinus by nasal endoscopy].

PMID- 24680345
TI  - [Primary squamous cell carcinoma of thyroid: a case report].

PMID- 24680346
TI  - [A case report of the ameloblastic fibroma in nasal septum].

PMID- 24680347
TI  - [Management of Madelung syndrome: report of 1 case].

PMID- 24680348
TI  - [A case of huge thyroglossal duct cyst blocking throat and trachea].

PMID- 24680349
TI  - [Report of a case with the ultimobranchial body cyst of thyroid].

PMID- 24680351
TI  - [Dialectic of the clinical otologist training].

PMID- 24680350
TI  - [A case of right juvenile nasopharyngeal angiofibroma involved parapharyngeal
      cystic degeneration].

PMID- 24680352
TI  - [Allergic rhinitis and TLR/MyD88 signaling pathway].

PMID- 24680353
TI  - [Progress in application of transoral robotic surgery in parapharyngeal space and
      infratemporal fossa].

PMID- 24680354
TI  - Vertical alignments of graphene sheets spatially and densely piled for fast ion
      diffusion in compact supercapacitors.
AB  - Supercapacitors with porous carbon structures have high energy storage capacity.
      However, the porous nature of the carbon electrode, composed mainly of carbon
      nanotubes (CNTs) and graphene oxide (GO) derivatives, negatively impacts the
      volumetric electrochemical characteristics of the supercapacitors because of poor
      packing density (<0.5 g cm(-3)). Herein, we report a simple method to fabricate
      highly dense and vertically aligned reduced graphene oxide (VArGO) electrodes
      involving simple hand-rolling and cutting processes. Because of their vertically
      aligned and opened-edge graphene structure, VArGO electrodes displayed high
      packing density and highly efficient volumetric and areal electrochemical
      characteristics, very fast electrolyte ion diffusion with rectangular CV curves
      even at a high scan rate (20 V/s), and the highest volumetric capacitance among
      known rGO electrodes. Surprisingly, even when the film thickness of the VArGO
      electrode was increased, its volumetric and areal capacitances were maintained. 

PMID- 24680355
TI  - Effect of thermomechanical aging on bond strength and interface morphology of
      glass fiber and zirconia posts bonded with a self-etch adhesive and a self
      adhesive resin cement to natural teeth.
AB  - STATEMENT OF PROBLEM: Information regarding the effect of thermomechanical aging
      (TMA) on the bond strength of luting cements to root canal dentin and endodontic
      posts is limited. PURPOSE: The purpose of this study was to investigate the
      effect of TMA on the bond strength of fiber and zirconia posts bonded to root
      canal dentin with 2 different resin cements with microtensile and scanning
      electron microscopic evaluation. MATERIAL AND METHODS: Eighty extracted single
      rooted human premolars were endodontically treated and restored with either a
      glass fiber post (FP) or a zirconia post (ZP) with 2 commercially available resin
      luting cements. The teeth were divided into 2 main groups. In the first group,
      posts (n=40) were bonded with a self-etch adhesive cement (SEAC). In the second
      group (n=40), posts were bonded using a self-adhesive cement (SAC). During the
      first aging phase, all specimens in each group were stored in distilled water for
      30 days at 37 degrees C. During the second phase, half of the specimens in each
      group were subjected to the TMA. The test groups were as follows: FP/SEAC,
      FP/SEAC+TMA, ZP/SEAC, ZP/SEAC+TMA, FP/SAC, FP/SAC+TMA, ZP/SAC, and ZP/SAC+TMA.
      The bond strength was measured with a microtensile test. Data were analyzed by 3
      way analysis of variance and the Tukey honest significant different test
      (alpha=.05). RESULTS: FP/SEAC at 30 days was higher than in the other groups.
      However, bond strength values were significantly reduced in this group after TMA
      (P<.001). CONCLUSIONS: Bond strength values and physical properties of SEAC with
      higher filler content were more affected by the TMA than those of SALC. According
      to scanning electron microscopic observation, TMA also affected the
      micromorphologic interface between the posts and the resin cements as well as
      between the resin cements and the root canal dentin.

PMID- 24680356
TI  - Effect of polyhedral silsesquioxane (POSS) on the flexural strength and color of
      interim materials.
AB  - STATEMENT OF PROBLEM: Polyhedral silsesquioxane (POSS) nanofillers can reinforce
      interim materials. However, the interaction between the POSS and the brand and
      its effect on color are unknown. PURPOSE: The purpose of this study was to
      determine the effect on the flexural strength, color, and color stability of 4
      commercially available interim materials modified with 1 wt% POSS. MATERIAL AND
      METHODS: Four commercial interim resin materials were used in this study: Jet,
      Trim, Temphase, and Protemp. The flexural strength of the interim materials was
      measured with and without 1 wt% POSS with an Instron universal testing machine.
      The color of the interim material and the material with 1 wt% POSS were
      evaluated, followed by the evaluation of the color change after coffee staining.
      The data were analyzed with a 2-way analysis of variance (ANOVA) followed by the
      Tukey standardized range test (HSD) to determine statistical significance
      (alpha=.05). RESULTS: POSS enhanced the flexural strength of Protemp and Trim but
      had no effect on Temphase and Jet. POSS had a significant affect on the color
      (L*, a*, b*), but only 2 pairwise differences (in L* Trim versus Trim POSS and in
      a* Temphase versus Temphase POSS) were detected. The effect of POSS on color
      change after coffee staining was minimal. POSS only had a significant effect on
      DeltaL, and only 1 pairwise difference was detected (Temphase versus Temphase
      POSS). The collapsed means revealed significant differences in color change among
      brands after coffee staining. CONCLUSIONS: The reinforcement effect of POSS on
      flexural strength depended on the brand, suggesting that the chemistry of the
      resin affects the ability of POSS to modify mechanical properties. POSS affected
      the initial color of the interim materials but had little effect on the color
      change after coffee staining.

PMID- 24680357
TI  - Effect of modifying the screw access channels of zirconia implant abutment on the
      cement flow pattern and retention of zirconia restorations.
AB  - STATEMENT OF PROBLEM: The effect of managing the screw access channels of
      zirconia implant abutments in the esthetic zone has not been extensively
      evaluated. PURPOSE: The purpose of this study was to determine the effect of an
      insert placed within the screw access channel of an anterior zirconia implant
      abutment on the amount of cement retained within the restoration-abutment system
      and on the dislodging force. MATERIAL AND METHODS: Thirty-six paired zirconia
      abutments and restorations were fabricated by computer-aided design and computer
      aided manufacturing and were divided into 3 groups: open abutment, with the screw
      access channel unfilled; closed abutment, with the screw access channel sealed;
      and insert abutment, with a thin, tubular metal insert projection continuous with
      the screw head and placed into the abutment screw access channel. The
      restorations were cemented to the abutments with preweighed eugenol-free zinc
      oxide cement (TempBond NE). Excess cement was removed, and the weight of the
      cement that remained in the restoration-abutment system was measured. Vertical
      tensile dislodging forces were recorded at a crosshead speed of 5 mm/min after
      incubation in a 37 degrees C water bath for 24 hours. The specimens were examined
      for the cement flow pattern into the screw access channel after dislodgement.
      Data were analyzed with ANOVA, followed by multiple comparisons by using the
      Tukey honestly significant difference test (alpha = .05). RESULTS: The mean
      (standard deviation) of retentive force values ranged from 108.1 +/- 29.9 N to
      148.3 +/- 21.0 N. The retentive force values differed significantly between the
      insert abutment and both the open abutment (P < .05) and closed abutment groups
      (P < .01). Distinct patterns of cement failure were noted. The weight of the
      cement that remained in the system differed significantly, with both open
      abutment and insert abutment being greater than closed abutment (P < .05).
      CONCLUSION: Modifying the internal configuration of the screw access channel of
      an esthetic zirconia implant abutment with a metal insert significantly affected
      both the cement retained within the abutment itself and the retention
      capabilities of the zirconia restoration cemented with TempBond NE cement.

PMID- 24680358
TI  - Myelomatous meningitis: a rare neurological involvement in complete remission of
      Multiple Myeloma.

PMID- 24680360
TI  - Renal tumor contact surface area: a novel parameter for predicting complexity and
      outcomes of partial nephrectomy.
AB  - BACKGROUND: The contact surface area (CSA) of a tumor with adjacent renal
      parenchyma may determine the complexity and thus the perioperative outcomes of
      partial nephrectomy (PN). OBJECTIVE: We devised a novel imaging parameter, renal
      tumor CSA, and correlate it with perioperative outcomes in patients undergoing
      PN. DESIGN, SETTING, AND PARTICIPANTS: Of 200 patients undergoing PN for a tumor
      (January 2010 to August 2011), 162 had renal protocol computed tomography
      scanning data available. CSA was calculated using image-rendering software
      (Synapse 3D, Fujifilm), and interobserver variability was determined between
      three independent observers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: CSA
      was correlated to baseline demographics and perioperative outcomes as a
      continuous and categorical variable using multivariable logistic regression
      analysis. The ability of CSA to predict adverse perioperative events was compared
      with demographic factors and nephrometry scoring systems. RESULTS AND
      LIMITATIONS: The mean tumor size was 3.1cm; CSA was 18.3 cm(2). CSA >=20 cm(2)
      correlated with adverse tumor characteristics (greater tumor size, volume, and
      complexity) and perioperative outcomes (more parenchymal volume loss, blood loss,
      and complications) compared with CSA <20 cm(2). On multivariable logistic
      regression, CSA independently predicted operative time, complications, hospital
      stay, and renal functional outcomes. This predictive ability of CSA was superior
      to the other parameters evaluated. CONCLUSIONS: CSA is a novel imaging parameter
      that quantifies the CSA of renal tumor with adjacent parenchyma. Our preliminary
      data indicate that CSA correlates with PN outcomes. If validated externally in a
      larger cohort, CSA could be incorporated into future versions of nephrometry
      scoring systems. PATIENT SUMMARY: In this study we outline the method of
      calculating the contact surface area (CSA) of renal tumors with the surrounding
      normal kidney using image-rendering software. We found that CSA correlates with a
      number of important surgical outcomes including operative time, loss of renal
      function, and complications.

PMID- 24680359
TI  - Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year
      follow-up of the ARO 96-02/AUO AP 09/95 trial.
AB  - BACKGROUND: Local failure after radical prostatectomy (RP) is common in patients
      with cancer extending beyond the capsule. Three prospectively randomized trials
      demonstrated an advantage for adjuvant radiotherapy (ART) compared with a wait
      and-see (WS) policy. OBJECTIVE: To determine the efficiency of ART after a 10-yr
      follow-up in the ARO 96-02 study. DESIGN, SETTING, AND PARTICIPANTS: After RP,
      388 patients with pT3 pN0 prostate cancer (PCa) were randomized to WS or three
      dimensional conformal ART with 60 Gy. The present analysis focuses on intent-to
      treat patients who achieved an undetectable prostate-specific antigen after RP
      (ITT2 population)--that is, 159 WS plus 148 ART men. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The primary end point of the study was progression-free
      survival (PFS) (events: biochemical recurrence, clinical recurrence, or death).
      Outcomes were compared by log-rank test. Cox regression analysis served to
      identify variables influencing the course of disease. RESULTS AND LIMITATIONS:
      The median follow-up was 111 mo for ART and 113 mo for WS. At 10 yr, PFS was 56%
      for ART and 35% for WS (p<0.0001). In pT3b and R1 patients, the rates for WS even
      dropped to 28% and 27%, respectively. Of all 307 ITT2 patients, 15 died from PCa,
      and 28 died for other or unknown reasons. Neither metastasis-free survival nor
      overall survival was significantly improved by ART. However, the study was
      underpowered for these end points. The worst late sequelae in the ART cohort were
      one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of
      rectum toxicity. No grade 4 events occurred. CONCLUSIONS: Compared with WS, ART
      reduced the risk of (biochemical) progression with a hazard ratio of 0.51 in pT3
      PCa. With only one grade 3 case of late toxicity, ART was safe. PATIENT SUMMARY:
      Precautionary radiotherapy counteracts relapse after surgery for prostate cancer
      with specific risk factors.

PMID- 24680361
TI  - A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy
      for upper tract urothelial carcinoma.
AB  - CONTEXT: The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC)
      remains poorly defined for the management of upper tract urothelial carcinoma
      (UTUC), although some studies suggest a benefit. OBJECTIVE: To update the current
      evidence on the role of NC and AC for UTUC patients. EVIDENCE ACQUISITION: We
      searched for all studies investigating NC or AC for UTUC in Medline, Embase, the
      Cochrane Central Register of Controlled Trials, and abstracts from the American
      Society of Clinical Oncology meetings prior to February 2014. A systematic review
      and meta-analysis were performed. EVIDENCE SYNTHESIS: No randomized trials
      investigated the role of AC for UTUC. There was one prospective study (n=36)
      investigating adjuvant carboplatin-paclitaxel and nine retrospective studies,
      with a total of 482 patients receiving cisplatin-based or non-cisplatin-based AC
      after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three
      cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS)
      was 0.43 (95% confidence interval [CI], 0.21-0.89; p=0.023) compared with those
      who received surgery alone. For disease-free survival (DFS), the pooled HR across
      two studies was 0.49 (95% CI, 0.24-0.99; p=0.048). Benefit was not seen for non
      cisplatin-based regimens. For NC, two phase 2 trials demonstrated favorable
      pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) <=
      93%. Across two retrospective studies investigating NC, there was a DSS benefit,
      with a pooled HR of 0.41 (95% CI, 0.22-0.76; p=0.005). CONCLUSIONS: There appears
      to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is
      limited by the retrospective nature of studies and their relatively small sample
      size. NC appears to be promising, but more trials are needed to confirm its
      utility. PATIENT SUMMARY: After a comprehensive search of studies examining the
      role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows
      that cisplatin-based adjuvant chemotherapy was beneficial for prolonging
      survival.

PMID- 24680362
TI  - Seminal hyperviscosity is not associated with semenogelin degradation or sperm
      deoxyribonucleic acid damage: a prospective study of infertile couples.
AB  - OBJECTIVE: To investigate the association between seminal hyperviscosity, the
      extent of semenogelin degradation, and sperm DNA integrity (DNA fragmentation
      index [DFI] and high DNA stainability [HDS]) in semen from infertile couples.
      DESIGN: Prospective study. SETTING: University-affiliated fertility center.
      PATIENT(S): Twenty-four consecutive infertile couples with moderate or high
      seminal viscosity (hyperviscosity group) and 25 consecutive infertile couples
      with normal semen viscosity (control group) undergoing standard IVF.
      INTERVENTION(S): Semen volume and seminal hyperviscosity, sperm concentration,
      motility, and morphology, level of semenogelin degradation (by immunoblotting),
      and sperm chromatin damage (by sperm chromatin structure assay and expressed as
      %DFI and %HDS) were evaluated. MAIN OUTCOME MEASURES(S): Sperm %DFI and %HDS in
      the hyperviscosity group and the control group and the relationship between the
      extent of semenogelin degradation and seminal viscosity. RESULT(S): Semen volume
      in couples with moderate and high seminal viscosity was significantly lower as
      compared with the control group. In addition, total motility and normal
      morphology were significantly lower in the couples with high seminal viscosity as
      compared with the control group; however, there were no significant differences
      in sperm %DFI and %HDS between the hyperviscosity group and the control group. In
      addition, there was no relationship between the extent of semenogelin degradation
      and seminal viscosity. CONCLUSION(S): Our data suggest that seminal
      hyperviscosity (a posttesticular factor) is not an important cause of sperm DNA
      damage. Moreover, seminal hyperviscosity is not related to the degree of
      semenogelin degradation.

PMID- 24680363
TI  - Recurrent miscarriages, innate immunity, and autoimmune reaction to chlamydial 60
      kDa heat shock protein--is there an association?
AB  - OBJECTIVE: To evaluate a potential association of immunity to the Chlamydia
      trachomatis 60kDa heat shock protein (ChlamHSP60) and recurrent miscarriages.
      DESIGN: Prospective study. SETTING: Outpatient miscarriage clinic of a university
      based hospital. PATIENT(S): 120 asymptomatic women with a history of recurrent
      miscarriages. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Determination of
      serum immunoglobulin G (IgG) antibodies (Ab) to ChlamHSP60 and human HSP60 and,
      in parallel, mannose-binding lectin (MBL) and the total hemolytic complement
      (CH50); medical history and clinical examination, including multiple relevant
      laboratory determinants. RESULT(S): ChlamHSP60 Ab were detected in 24 (20%) of
      120 patients. Antibodies to human HSP60 were found in 19 (15.8%) of 120 patients,
      and more frequently in individuals who tested positive for ChlamHSP60. ChlamHSP60
      were statistically significantly associated with antichlamydial IgG Ab. However,
      antibodies to ChlamHSP60 were not related to medical history, the number of
      abortions, or the time frame of fetal loss. ChlamHSP60 antibodies were not
      associated with the relevant variables of the coagulation cascade, a panel of
      autoimmune parameters including thyroid autoimmunity, deficiencies of the
      complement system (low MBL), or with antibodies to common infectious diseases. No
      statistically significant differences were was found when comparing the
      prevalence of ChlamHSP60 Ab in the study group with recurrent miscarriages and 90
      controls (women attending for an annual pelvic examination). CONCLUSION(S):
      Immunity to ChlamHSP60 does not play a major role in the etiology of recurrent
      miscarriages.

PMID- 24680364
TI  - Is the modified natural in vitro fertilization cycle justified in patients with
      "genuine" poor response to controlled ovarian hyperstimulation?
AB  - OBJECTIVE: To examine whether patients with poor ovarian response (POR) during
      conventional IVF/intracytoplasmic sperm injection (ICSI) treatment cycle may
      benefit from a modified natural cycle (MNC)-IVF. DESIGN: Cohort historic study.
      SETTING: Tertiary, university-affiliated medical center. PATIENT(S): One hundred
      eleven patients with POR, defined according to the Bologna criteria, who
      underwent a subsequent MNC-IVF within 3 months of the previous failed
      conventional IVF/ICSI cycle. The elimination of bias in this selection, for the
      purposes of this study, was achieved by including only a subgroup of "genuine"
      poor responder patients, those who yielded up to three oocytes after controlled
      ovarian hyperstimulation (COH) with a minimal gonadotropin daily dose of 300 IU.
      INTERVENTION(S): Modified natural cycle IVF protocol with GnRH antagonist (GnRH
      a) supplementation. Gonadotropin-releasing hormone antagonist treatment was
      started when a follicle of 13 mm was present. Two to three ampules of hMG were
      coadministered daily during the GnRH-a treatment. MAIN OUTCOME MEASURE(S): Live
      birth rate, pregnancy rate (PR), number of oocytes retrieved, and number of
      embryos transferred. RESULT(S): Live birth rate in "genuine" poor ovarian
      responders was <1%. Furthermore, in the subgroup of patients with POR who
      underwent a previous conventional IVF/ICSI cycle with a yield of only one oocyte,
      no pregnancies were achieved during the MNC-IVF cycle. CONCLUSION(S): Modified
      natural cycle-IVF is of no benefit for genuine poor ovarian responders and the
      option of egg donation should be seriously considered for this population.

PMID- 24680365
TI  - Reply of the authors.

PMID- 24680366
TI  - Hematoureter due to endometriosis.
AB  - OBJECTIVE: To report the laparoscopic management of a rare case of hematoureter
      due to endometriosis in a young woman with multiple genitourinary anomalies.
      DESIGN: Video demonstration of a surgical technique and review of genitourinary
      endometriosis. SETTING: Hospital. PATIENT(S): A 17-year-old nulliparous woman
      with multiple genitourinary anomalies presented with pelvic pain and unilateral
      retroperitoneal mass. The patient had uterine didelphys, a history of left
      nephrectomy, and partial ureter resection as an infant. She had a partial
      resection of a left transverse vaginal septum due to hematocolpos at age 12. A
      preoperative magnetic resonance imaging (MRI) scan revealed a left
      retroperitoneal mass with extension to the paravesical region, reaccumulation of
      the hematocolpos behind the partially resected left transverse vaginal septum,
      and a dilated left uterine horn with hematometra. INTERVENTION(S): Laparoscopic
      management of hematoureter due to intrinsic endometriosis. MAIN OUTCOME
      MEASURE(S): Intraoperative findings showed uterus didelphys with dilated left
      horn, normal right horn, and normal right and left fallopian tubes and ovaries.
      The left transverse vaginal septum was resected vaginally, and the hematocolpos
      and hematometra drained. The left uterine horn and cervix were laparoscopically
      resected. The left-side serpiginous retroperitoneal mass was dissected from the
      pelvic sidewall, ligated, and transected, with spillage of thick, brown liquid.
      The pathology of the mass wall was smooth muscle and transitional epithelium
      consistent with ureter, in addition to hemorrhage and glandular structures
      consistent with endometriosis. Endometriosis was also present in the serosa of
      the left uterine horn. Thus, the left retroperitoneal mass was the left ureter
      remnant, which acquired endometriosis and collected menstrual debris, resulting
      in hematoureter. CONCLUSION(S): Two major pathologic types of ureteral
      endometriosis have been described: intrinsic, as occurred in this patient, and
      extrinsic. Women with mullerian anomalies, vaginal obstruction, or imperforate
      hymen are at higher risk of endometriosis. Prior urogenital surgery can further
      complicate and distort the anatomy. Thus, a preoperative understanding of the
      patient's urogenital anomalies is important to consider the differential
      diagnoses and anticipate surgical needs.

PMID- 24680367
TI  - Male infertility biomarkers and genomic aberrations in azoospermia.

PMID- 24680369
TI  - Anabolic steroid abuse: a paradox of manliness.

PMID- 24680368
TI  - Influence of oral contraceptives on anthropomorphometric, endocrine, and
      metabolic profiles of anovulatory polycystic ovary syndrome patients.
AB  - OBJECTIVE: To evaluate the influence of oral contraceptive pills (OCPs) on
      anthromorphometric, endocrine, and metabolic parameters in women with polycystic
      ovary syndrome (PCOS). DESIGN: Retrospective cross-sectional cohort study for the
      period 1993-2011. SETTING: Tertiary university hospital. PATIENT(S): PCOS
      patients, who never, ever, or at time of screening were using OCPs were included.
      A total of 1,297 patients, of whom 827 were white, were included. All PCOS
      patients diagnosed according to the Rotterdam 2003 consensus criteria were
      divided into three groups: current users, (n = 76; 6% of total), ever users (n =
      1,018; 78%), and never users (n = 203; 16%). Ever users were subdivided based on
      the OCP-free interval. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Anthromorphometric (blood pressure, cycle duration) and ultrasound (follicle
      count, mean ovarian volume) parameters, endocrine (SHBG, testosterone, free
      androgen index, antimullerian hormone [AMH]) and lipid profiles. RESULT(S):
      Current users and ever users were compared with never users. In current users,
      SHBG was increased and androgen levels decreased. Patients with an OCP-free
      interval of <1 year had a higher mean follicle count, higher AMH level, and
      increased serum androgen level compared with never users. SHBG levels remained
      increased until 5-10 years after cessation of OCP use. CONCLUSION(S): OCP use
      causes a milder phenotypic presentation of PCOS regarding hyperandrogenism.
      However, it does not alter parameters associated with increased health risks.

PMID- 24680370
TI  - Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating
      the expression of transgelin 2.
AB  - Paclitaxel (PTX) is a first-line antineoplastic drug that is commonly used in
      clinical chemotherapy for breast cancer treatment. However, the occurrence of
      drug resistance in chemotherapeutic treatment has greatly restricted its use.
      There is thus an urgent need to find ways of reversing paclitaxel chemotherapy
      resistance in breast cancer. Plant-derived agents have great potential in
      preventing the onset of the carcinogenic process and enhancing the efficacy of
      mainstream antitumor drugs. Paeonol, a main compound derived from the root bark
      of Paeonia suffruticosa, has various biological activities, and is reported to
      have reversal drug resistance effects. This study established a paclitaxel
      resistant human breast cancer cell line (MCF-7/PTX) and applied the dual
      luciferase reporter gene assay, MTT assay, flow cytometry, transfection assay,
      Western blotting and the quantitative real-time polymerase chain reaction (qRT
      PCR) to investigate the reversing effects of paeonol and its underlying
      mechanisms. It was found that transgelin 2 may mediate the resistance of MCF
      7/PTX cells to paclitaxel by up-regulating the expressions of the adenosine
      triphosphate binding cassette transporter proteins, including P-glycoprotein (P
      gp), multidrug resistance associated protein 1 (MRP1), and breast cancer
      resistance protein (BCRP). Furthermore, the ability of paeonol to reverse
      paclitaxel resistance in breast cancer was confirmed, with a superior 8.2-fold
      reversal index. In addition, this study found that paeonol down-regulated the
      transgelin 2-mediated paclitaxel resistance by reducing the expressions of P-gp,
      MRP1, and BCRP in MCF-7/PTX cells. These results not only provide insight into
      the potential application of paeonol to the reversal of paclitaxel resistance,
      thus facilitating the sensitivity of breast cancer chemotherapy, but also
      highlight a potential role of transgelin 2 in the development of paclitaxel
      resistance in breast cancer. 

PMID- 24680371
TI  - Concentration of di(2-ethylhexyl) phthalate (DEHP) in foods and its dietary
      exposure in China.
AB  - Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer used in food contact
      materials that has been reported as an endocrine disruptor. In the present study,
      DEHP concentrations were analyzed in foods in order to determine dietary exposure
      among the Chinese population, including the general population (aged 2-100) and
      four age group, that is children aged 2-6, adolescent aged 7-12, young people
      aged 13-17 and adults aged 18 years old and above. 1704 food samples were
      collected during 2011-2012 and categorized into 12 food groups which covered
      major foods in China. Food consumption data were taken from China National
      Nutrient and Health Survey which was performed in 2002 and includes data from
      68,959 subjects. Mean concentrations of DEHP were combined with individual food
      consumption data to estimate dietary exposure. It was found that DEHP levels in
      foods ranged from not detected to 3.41 mg/kg, with highest mean values in meat
      (0.23 mg/kg) and vegetable oils (0.21 mg/kg). Mean dietary intakes of DEHP in the
      general population, children, and adults were 2.34, 4.51, 2.03 MUg/kg bw per day,
      respectively. The 97.5% intakes in these populations were 5.22, 8.43, 3.64 MUg/kg
      bw per day, respectively. The main food sources of DEHP dietary intake were
      cereals (39.44%), drinking water (16.94%) and meat (15.81%) in children, and
      cereals (44.57%), meat (15.70%) and drinking water (12.28%) for adults. These
      findings suggested that dietary exposure to DEHP among Chinese population was
      lower than tolerable daily intake of DEHP and there are no health concerns based
      on generally accepted exposure limits.

PMID- 24680373
TI  - Orexin receptor antagonists: a new treatment for insomnia?

PMID- 24680372
TI  - Safety and efficacy of suvorexant during 1-year treatment of insomnia with
      subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Suvorexant (MK-4305) is an orexin receptor antagonist shown to be
      efficacious for insomnia over 3 months. We aimed to assess its clinical profile
      during and after 1 year of treatment. METHODS: We did a randomised, placebo
      controlled, parallel-group trial at 106 investigational centres in the Americas,
      Australia, Europe, and South Africa from December, 2009, to August, 2011.
      Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were
      assigned using a computer-generated randomised allocation schedule to receive
      nightly suvorexant (40 mg for patients younger than 65 years, 30 mg for patients
      aged 65 years or older) or placebo at a 2:1 ratio for 1 year with a subsequent 2
      month randomised discontinuation phase in which patients on suvorexant either
      continued suvorexant or were abruptly switched to placebo while patients on
      placebo remained on placebo. Treatment assignment was masked from patients and
      investigators. The primary objective was to assess the safety and tolerability of
      suvorexant for up to 1 year. Secondary objectives were to assess the efficacy of
      suvorexant for improving patient-reported subjective total sleep time (sTST) and
      time to sleep onset (sTSO) over the first month of treatment. Efficacy endpoints
      over the first month were assessed with a mixed model with terms for baseline
      value of the response variable, age, sex, region, treatment, time, and treatment
      by time interaction. This trial is registered with ClinicalTrials.gov, number
      NCT01021813. FINDINGS: 322 (62%) of 522 patients randomly assigned to receive
      suvorexant and 162 (63%) of 259 assigned to receive placebo completed the 1-year
      phase. Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced
      any adverse events compared with 164 (64%) of 258 treated with placebo. Serious
      adverse events were recorded in 27 patients (5%) who received suvorexant and 17
      (7%) who received placebo. The most common adverse event, somnolence, was
      reported for 69 patients (13%) who received suvorexant and seven (3%) who
      received placebo. At month 1, suvorexant (517 patients in the efficacy
      population) showed greater efficacy than placebo (254 in the efficacy population)
      in improving sTST (38.7 min vs 16.0 min; difference 22.7, 95% CI 16.4 to 29.0;
      p<0.0001) and sTSO (-18.0 min vs -8.4 min, difference -9.5, -14.6 to -4.5;
      p=0.0002). INTERPRETATION: Our findings show that suvorexant was generally safe
      and well tolerated over 1 year of nightly treatment in patients with insomnia,
      with efficacy noted for subjective measures of sleep onset and maintenance.
      FUNDING: Merck & Co Inc.

PMID- 24680374
TI  - Analytical techniques for characterization of cyclodextrin complexes in aqueous
      solution: a review.
AB  - Cyclodextrins are cyclic oligosaccharides endowed with a hydrophilic outer
      surface and a hydrophobic inner cavity, able to form inclusion complexes with a
      wide variety of guest molecules, positively affecting their physicochemical
      properties. In particular, in the pharmaceutical field, cyclodextrin complexation
      is mainly used to increase the aqueous solubility and dissolution rate of poorly
      soluble drugs, and to enhance their bioavailability and stability. Analytical
      characterization of host-guest interactions is of fundamental importance for
      fully exploiting the potential benefits of complexation, helping in selection of
      the most appropriate cyclodextrin. The assessment of the actual formation of a
      drug-cyclodextrin inclusion complex and its full characterization is not a simple
      task and often requires the use of different analytical methods, whose results
      have to be combined and examined together. The purpose of the present review is
      to give, as much as possible, a general overview of the main analytical tools
      which can be employed for the characterization of drug-cyclodextrin inclusion
      complexes in solution, with emphasis on their respective potential merits,
      disadvantages and limits. Further, the applicability of each examined technique
      is illustrated and discussed by specific examples from literature. 

PMID- 24680375
TI  - Use of herd management programmes to improve the reproductive performance of
      dairy cattle.
AB  - There has been a long history of herd health and production management programmes
      in many dairy industries around the world, but evidence for the efficacy of such
      programmes is limited. In response to a perceived decline in fertility of dairy
      cows, a herd reproductive management programme (InCalf) was introduced in New
      Zealand in 2007. This programme uses a management cycle approach that includes an
      assessment of the current herd status, identification of areas for improvement,
      development of a plan, implementation of this plan and finally a review process.
      The programme uses facilitators who work with farmers either in a one-to-one
      manner or in a formalised group setting that involves a series of meetings over a
      12-month period (the farmer action group). The hypothesis that involvement in a
      reproductive management programme would improve herd reproductive performance was
      tested using a herd-level controlled randomised study (the National Herd
      Fertility Study) involving herds in four geographic regions of New Zealand over 2
      years. Within each region, herds were ranked on the basis of the 6-week in-calf
      rate (i.e. the proportion of the herd pregnant in the first 6 weeks of the
      seasonal breeding programme) in the year preceding commencement of the study and
      then randomly assigned to be involved in a farmer action group or left as
      untreated controls. The key outcome variable of the study was the 6-week in-calf
      rate. Pregnancy diagnosis was undertaken at 12 weeks after the start of the
      seasonal breeding programme, which allowed determination of conception dates and
      hence calculation of the 6-week in-calf rate. Additional measurements including
      heifer live weight and body condition score (pre-calving and pre-mating) were
      undertaken to test whether treatment resulted in measurable changes in some of
      the key determinants of herd reproductive performance. Involvement in the farmer
      action group of InCalf resulted in a 2 percentage point increase in the 6-week in
      calf rate (P=0.05). The following additional observations were made in herds
      involved in the farmer action group relative to control herds: heifers had live
      weight closer to target; the pre-mating body condition score of cows was higher;
      and oestrous detection rates were higher. It was concluded that involvement in
      this herd reproductive management programme improved reproductive outcomes in
      this New Zealand study. However, to achieve substantial improvements in herd
      reproductive performance at the regional or national level a greater response to
      the programme and a high uptake of such programmes is required, as well as use of
      other industry-level tools such as genetic management programmes. 

PMID- 24680376
TI  - Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic
      rats.
AB  - Diabetes mellitus results in neuronal damage caused by increased intracellular
      glucose leading to oxidative stress. Recent evidence revealed the potential of
      ginger for reducing diabetes-induced oxidative stress markers. The aim of this
      study is to investigate, for the first time, whether the antioxidant properties
      of ginger has beneficial effects on the structural brain damage associated with
      diabetes. We investigated the observable neurodegenerative changes in the frontal
      cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin
      (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day).
      Sections of frontal cortex, dentate gyrus, and cerebellum were stained with
      hematoxylin and eosin and examined using light microscopy. In addition,
      quantitative immunohistochemical assessments of the expression of inducible NO
      synthase (iNOS), tumor necrosis factor (TNF)-alpha, caspase-3, glial fibrillary
      acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our
      results revealed a protective role of ginger on the diabetic brain via reducing
      oxidative stress, apoptosis, and inflammation. In addition, this study revealed
      that the beneficial effect of ginger was also mediated by modulating the
      astroglial response to the injury, reducing AChE expression, and improving
      neurogenesis. These results represent a new insight into the beneficial effects
      of ginger on the structural alterations of diabetic brain and suggest that ginger
      might be a potential therapeutic strategy for the treatment of diabetic-induced
      damage in brain.

PMID- 24680377
TI  - Morphological and glycan features of the camel oviduct epithelium.
AB  - This study describes regional differences in the oviduct of the one-humped camel
      (Camelus dromedarius) during the growth phase (GP) and the mature phase (MP) of
      the follicular wave by means of morphometry, scanning electron microscopy (SEM)
      and glycohistochemistry investigations. Epithelium height significantly increased
      in the ampulla and decreased in the isthmus passing from the GP to the MP. Under
      SEM, non-ciliated cells displayed apical blebs (secretory) or short microvilli.
      Cilia glycocalyx expressed glycans terminating with sialic acid linked alpha2,6
      to Gal/GalNAc (SNA affinity) throughout the oviducts of GP and MP and sialic acid
      linked alpha2,3 to Galbeta1,3GalNAc (MAL II and KOH-sialidase (K-s)-PNA staining)
      throughout the MP oviducts. Non-ciliated cells displayed lectin-binding sites
      from the supra-nuclear cytoplasm to the luminal surface. Ampulla non-ciliated
      cells showed O-linked (mucin-type) sialoglycans (MAL II and K-s-PNA) during GP
      and MP and N-linked sialoglycans (SNA) during the MP. Isthmus non-ciliated cells
      expressed SNA reactivity in GP and MP, also K-s-PNA binders in MP, and MAL II and
      PNA affinity (Galbeta1,3GalNAc) during GP. Galbeta1,3GalNAc was sialilated in the
      non-ciliated cells of GP UTJ. Luminal surface lacked of Galbeta1,3GalNAc in GP
      and MP, whereas it expressed alpha2,6- and alpha2,3-linked sialic acids. In GP
      intraluminal substance reacted with SNA, MAL II, K-s-PNA in ampulla and only with
      MAL II in the isthmus and UTJ. These results demonstrate that the morphology and
      the glycan pattern of the camel oviductal epithelium vary during the follicular
      wave and that could relate to the region-specific functions.

PMID- 24680378
TI  - Haematological toxicity in adult patients receiving craniospinal irradiation-
      indication of a dose-bath effect.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the
      correlation between the haematological toxicity observed in patients treated with
      craniospinal irradiation, and the dose distribution in normal tissue,
      specifically the occurrence of large volumes exposed to low dose. MATERIALS AND
      METHODS: Twenty adult male patients were included in this study; eight treated
      with helical tomotherapy (HT), and twelve with three-dimensional conformal
      radiation therapy. The relative volume of red bone marrow and body that was
      exposed to low dose (i.e. the so-called dose bath) was evaluated and correlated
      with nadir blood values during treatment, i.e. the severity of anaemia,
      leukopaenia, and thrombocytopaenia. The correlation was tested for different dose
      levels representing the dose bath using the Pearson product-moment correlation
      method. RESULTS: We found a significant correlation between the volume of red
      bone marrow exposed to low dose and the severity of thrombocytopaenia during
      treatment. Furthermore, for the HT patients, a significant correlation was found
      between the relative volume of the body exposed to low dose and the severity of
      anaemia and leukopenia. CONCLUSIONS: The severity of haematological toxicity
      correlated with the fraction of red bone marrow or body that was exposed to low
      dose.

PMID- 24680379
TI  - TRPM7 is involved in angiotensin II induced cardiac fibrosis development by
      mediating calcium and magnesium influx.
AB  - Cardiac fibrosis is involved in a lot of cardiovascular pathological processes.
      Cardiac fibrosis can block conduction, cause hypoxia, strengthen myocardial
      stiffness, create electrical heterogeneity, and hamper systolic ejection, which
      is associated with the development of arrhythmia, heart failure and sudden
      cardiac death. Besides the initial stimulating factors, the cardiac fibroblasts
      (CFs) are the principal responsible cells in the fibrogenesis cascade of events.
      TRPM7, a member of the TRPM (Melastatin) subfamily, is a non-selective cation
      channel, which permeates both Ca(2+) and Mg(2+). Here we demonstrated TRPM7
      expression in CFs, and 2-APB (TRPM7 inhibitor), inhibited Ang II-induced CTGF,
      alpha-SMA expression and CFs proliferation. Besides, knocking down TRPM7 by
      shRNA, we proved that TRPM7 mediated both calcium and magnesium changes in
      cardiac fibroblasts which contribute to fibrosis progress. This study suggested
      that TRPM7 should play a pivotal role in cardiac fibroblast functions associated
      to cardiac fibrosis development. 

PMID- 24680380
TI  - The effects of calcium channel blockade on proliferation and differentiation of
      cardiac progenitor cells.
AB  - Cardiogenesis depends on a tightly regulated balance between proliferation and
      differentiation of cardiac progenitor cells (CPCs) and their cardiomyocyte
      descendants. While exposure of early mouse embryos to Ca(2+) channel antagonists
      has been associated with abnormal cardiac morphogenesis, less is known about the
      consequences of Ca(2+) channel blockade on proliferation and differentiation of
      CPCs at the cellular level. Here we showed that at embryonic day (E) 11.5, the
      murine ventricles express several L-type and T-type Ca(2+) channel isoforms, and
      that the dihydropyridine Ca(2+) channel antagonist, nifedipine, blunts
      isoproterenol induced increases in intracellular Ca(2+). Nifedipine mediated
      Ca(2+) channel blockade was associated with a reduction in cell cycle activity of
      E11.5 CPCs and impaired assembly of the cardiomyocyte contractile apparatus.
      Furthermore, in cell transplantation experiments, systemic administration of
      nifedipine to adult mice receiving transplanted E11.5 ventricular cells
      (containing CPCs and cardiomyocytes) was associated with smaller graft sizes
      compared to vehicle treated control animals. These data suggest that
      intracellular Ca(2+) is a critical regulator of the balance between CPC
      proliferation and differentiation and demonstrate that interactions between
      pharmacological drugs and transplanted cells could have a significant impact on
      the effectiveness of cell based therapies for myocardial repair. 

PMID- 24680382
TI  - Is autoimmune thyroid dysfunction a risk factor for gestational diabetes?
AB  - OBJECTIVE: Some recent studies have related autoimmune thyroid dysfunction and
      gestational diabetes (GD). The common factor for both conditions could be the
      existence of pro-inflammatory homeostasis. The study objective was therefore to
      assess whether the presence of antithyroid antibodies is related to the
      occurrence of GD. MATERIAL AND METHODS: Fifty-six pregnant women with serum TSH
      levels >= 2.5 mU/mL during the first trimester were retrospectively studied.
      Antithyroid antibodies were measured, and an O'Sullivan test was performed. GD
      was diagnosed based on the criteria of the Spanish Group on Diabetes and
      Pregnancy. RESULTS: Positive antithyroid antibodies were found in 21 (37.50%)
      women. GD was diagnosed in 15 patients, 6 of whom (10.71%) had positive
      antibodies, while 9 (16.07%) had negative antibodies. Data were analyzed using
      exact logistic regression by LogXact-8 Cytel; no statistically significant
      differences were found between GD patients with positive and negative
      autoimmunity (OR = 1.15 [95%CI = 0.28-4.51]; P=1.00). CONCLUSIONS: The presence
      of thyroid autoimmunity in women with TSH above the recommended values at the
      beginning of pregnancy is not associated to development of GD. However, GD
      prevalence was higher in these patients as compared to the Spanish general
      population, suggesting the need for closer monitoring in pregnant women with TSH
      levels >= 2.5 mU/mL.

PMID- 24680383
TI  - Prevalence of hyperandrogenism and polycystic ovary syndrome in female to male
      transsexuals.
AB  - INTRODUCTION: Prevalence of hyperandrogenism (HA), including the polycystic ovary
      syndrome (PCOS), in female-to-male transsexuals (FMT) is high. This has been
      related to metabolic syndrome (MS), which appears to increase cardiovascular
      morbidity and mortality throughout cross-sex hormone (CSH) therapy. OBJECTIVES:
      To assess the prevalence of HA and PCOS in FMT patients before the start of CSH
      therapy, and their association to MS and its components, insulin resistance (IR)
      and other cardiovascular risk (CVR) factors. MATERIALS AND METHODS: Seventy-seven
      FMTs underwent clinical and biochemical assessment for HA before the start of CSH
      therapy. CVR, IR, and other MS parameters were also assessed. RESULTS: Prevalence
      of HA was 49.4% (73.7% were cases of PCOS [Rotterdam criteria]), and prevalence
      of PCOS in the overall sample was 36.4%. Prevalence of MS was 38.4% and 51.7%
      according to ATP-III and IDF criteria respectively). MS (according to ATP-III and
      IDF criteria respectively) was found in 36.8% and 57.9% as compared to 25.6% and
      41% of patients with and without HA respectively (p<0.0001 and P<0.01
      respectively). Of total patients, 54.5% had normal weight (body mass index [BMI]
      18.5-24.9 kg.m(-2)), 26% were overweight (BMI 25-29.9 kg.m(-2)), and 19.5% were
      obese (BMI >= 30 kg.m(-2)). After adjusting for BMI, the comparison of hormonal,
      metabolic, and anthropometric parameters showed statistically significant
      differences in plasma glucose, HOMA-IR, and abdominal circumference (P<0.001 for
      all), as well as HDL cholesterol (HDL) (P=0.033), but not in total testosterone
      or calculated free testosterone levels. In the total sample, 27.3% had HDL levels
      less than 50mg/dL. CONCLUSIONS: Overall HA, and PCOS in particular, are highly
      prevalent in FMTs. HA and PCOS are related to early development of SM, IR, and
      other CVR factors with unknown consequences in adulthood.

PMID- 24680381
TI  - A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in
      children.
AB  - OBJECTIVE: To summarize the published effects of systemic glucocorticoid therapy
      on bone mineral density (BMD) and fractures in children. METHODS: We performed a
      systematic review and meta-analysis of existing literature, using Medline,
      CINAHL, and Cochrane databases to identify studies of BMD or fractures in
      children <=18 years taking systemic glucocorticoid therapy. We excluded studies
      of inhaled glucocorticoids, chemotherapy, and organ transplantation. Two authors
      reviewed abstracts for inclusion, read full-text articles to extract data, and
      rated each study using the Downs-Black scale. RESULTS: A total of 16 studies met
      eligibility criteria, including 10 BMD (287 children) and six fracture (37,819
      children) studies. Spine BMD was significantly lower (-0.18; 95% CI = -0.25; 
      0.10 g/cm(2)) in children taking glucocorticoid therapy, compared to age- and
      gender-matched healthy controls. Spine BMD was also lower (-0.14; 95% CI = -0.27;
      0.00 g/cm(2)) in children taking glucocorticoids, compared to children with the
      same disease not taking glucocorticoids. Incident clinical fracture rates varied
      from 2% to 33%. Morphometric vertebral fracture incidence ranged from 6% to 10%,
      and prevalence was 29-45%. CONCLUSION: Published data suggest that children
      treated with glucocorticoid therapy have lower spine BMD compared to healthy
      children. Whether children receiving glucocorticoid therapy have lower spine BMD
      compared to children with milder disease not requiring such therapy is not
      certain. Clinical and morphometric vertebral fractures are common, although only
      one study assessed fracture rates in healthy controls. Additional well-designed,
      prospective studies are needed to evaluate the skeletal effects of glucocorticoid
      therapy in children.

PMID- 24680384
TI  - Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily
      doses of 75 MUg.
AB  - BACKGROUND AND OBJECTIVES: Treatment of hypothyroid pregnant women is usually
      calculated based on weight (1 MUg/kg/day) and TSH levels. This study assessed the
      usefulness of treating these women with a fixed dose of 75 MUg/day. PATIENTS AND
      METHODS: All women with pregnancy diagnosed from January to August 2012 in the
      Vigo Health Area (Spain) without previous diagnosis of thyroid disease or
      thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by
      consecutive sampling. All 116 women in the sample were treated with a fixed daily
      dose of thyroxine 75 MUg-thyroxine levels were measured at two, four, and six
      months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher
      than 4.5 mUI/ml. RESULTS: A woman had a TSH level less than 0.3 mUI/ml in a test;
      reduction of thyroxine dose to 50 MUg/day allowed for maintaining TSH level
      within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml
      in one test; in all of them, increase in thyroxine dose to 100 MUg/day allowed
      for maintaining the level within the desired range until delivery. CONCLUSIONS:
      Fixed daily doses of thyroxine 75 MUg allowed for achieving goal TSH levels in
      most of our pregnant women with subclinical hypothyroidism, irrespective of their
      weight and baseline TSH level.

PMID- 24680385
TI  - Non-genomic actions of thyroid hormones: Molecular aspects.

PMID- 24680386
TI  - [For an open-door, more comfortable and humane intensive care unit. It is time
      for change].
AB  - The Intensive Care Unit is a wonderful place where lives are saved, but it is
      also a very harsh and unpleasant place where critically ill patients face
      terrible diseases in very adverse environmental conditions. We must change the
      design of the ICU and its organization; we must improve privacy, welfare and
      comfort of patients and families, following their personal and emotional demands.
      To free up the visiting hours and to improve family care are among our most
      urging matters, which we should delay no further. We must equip the ICUs with
      modern monitors and respirators but we must also invest in organization, design,
      environmental comfort and humanization. We need to redesign clinical practise so
      that ICU care becomes more agreeable and humane. We should put off this change no
      longer, since it is an imperative social and professional demand. 

PMID- 24680387
TI  - Cell transplantation therapy for a rat model of secondary lymphedema.
AB  - BACKGROUND: Although lymphedema is a progressive and lifelong condition,
      substantial advances in therapeutic intervention are limited. The development of
      a novel therapy for lymphedema is urgent for those patients suffering from it.
      The aim of this study was to investigate the usefulness of a new cell
      transplantation therapy in the rat tail model of secondary lymphedema. MATERIALS
      AND METHODS: We prepared two cell sources, human dermal microvascular endothelial
      cells (HDMECs) and lymphatic endothelial cells (LECs), which were collected from
      the resected normal dermis of patients with breast cancer. After the animal model
      of secondary lymphedema of the nude rats' tails was established, phosphate
      buffered saline, purified LECs, or unpurified HDMECs were injected in the rats'
      tails five times for more than 14 d. The evaluations were performed by measuring
      the circumference, fluorescence lymphography, and histologic analysis of the
      rats' tails between each group. RESULTS: The isolated cells by the simple
      immunomagnetic sorting from HDMECs were positive for a pan-endothelial marker
      (CD31) and lymphatic-specific markers (podoplanin, lymphatic vessel endothelial
      hyaluronan receptor-1 [LYVE-1], and prospero homebox 1 [Prox-1]), and were
      considered to be LECs. In the cell transplantation group, which was injected with
      human LECs, the circumference, lymphatic flow, and thickness of the skin of the
      rat tail became thinner than the groups injected with unpurified HDMECs or
      phosphate-buffered saline. Immunohistochemistry of the rat tails showed that the
      number of own lymphatic vessels was increased in the purified LEC transplantation
      group compared with the other groups. Furthermore, in the LEC transplantation
      group, some vessels were immunopositive for human-podoplanin or -LYVE-1 and the
      areas adjacent to the vessels were rat-podoplanin or -LYVE-1 immunopositive.
      CONCLUSIONS: Our findings indicate that cell transplantation therapy using human
      LECs improved the secondary lymphedema in the nude rat tail. This therapeutic
      strategy may merit clinical investigation in patients with lymphedema.

PMID- 24680388
TI  - Effect of ammonium nitrogen concentration on the ammonia-oxidizing bacteria
      community in a membrane bioreactor for the treatment of anaerobically digested
      swine wastewater.
AB  - A membrane bioreactor (MBR) was developed for the treatment of anaerobically
      digested swine wastewater and to investigate the effect of ammonium nitrogen
      concentration on biological nitrogen removal and ammonia-oxidizing bacteria (AOB)
      community structures. The MBR achieved a high NH4(+)-N removal efficiency of 0.08
      kgNMLSS(-1)d(-1) and removed 95% of the influent NH4(+)-N. The TN removal rate
      was highest of 82.62% at COD/TN and BOD5/TN ratios of 8.76 +/- 0.30 and 3.02 +/-
      0.09, respectively. With the decrease in ammonium nitrogen concentrations, the
      diversity of the AOB community declined and showed a simple pattern of DGGE.
      However, the AOB population size remained high, with abundance of 10(7)-10(9)
      copies mL(-1). With the decrease of ammonium nitrogen concentrations,
      Nitrosomonas eutropha gradually disappeared, whereas Nitrosomonas sp. OZK11
      showed constant adaptability to survive during each treatment stage. The
      selective effect of ammonium concentration on AOB species could be due to the
      affinity for NH4(+)-N. In this study, the changes of ammonium nitrogen
      concentrations in digested swine wastewater were found to have selective effects
      on the composition of AOB community, and biological nitrogen removal was improved
      by optimising the influencing parameters.

PMID- 24680389
TI  - Chemical vapor deposition growth of crystalline monolayer MoSe2.
AB  - Recently, two-dimensional layers of transition metal dichalcogenides, such as
      MoS2, WS2, MoSe2, and WSe2, have attracted much attention for their potential
      applications in electronic and optoelectronic devices. The selenide analogues of
      MoS2 and WS2 have smaller band gaps and higher electron mobilities, making them
      more appropriate for practical devices. However, reports on scalable growth of
      high quality transition metal diselenide layers and studies of their properties
      have been limited. Here, we demonstrate the chemical vapor deposition (CVD)
      growth of uniform MoSe2 monolayers under ambient pressure, resulting in large
      single crystalline islands. The photoluminescence intensity and peak position
      indicates a direct band gap of 1.5 eV for the MoSe2 monolayers. A back-gated
      field effect transistor based on MoSe2 monolayer shows n-type channel behavior
      with average mobility of 50 cm(2) V(-1) s(-1), a value much higher than the 4-20
      cm(2) V(-1) s(-1) reported for vapor phase grown MoS2. 

PMID- 24680390
TI  - Use of indocyanine green to facilitate intersegmental plane identification during
      robotic anatomic segmentectomy.

PMID- 24680391
TI  - Extracorporeal membrane oxygenation as a bridge to surgery for ischemic papillary
      muscle rupture.

PMID- 24680392
TI  - A novel and simple technique for correction of posterior leaflet prolapse due to
      chordal elongation or rupture.
AB  - OBJECTIVE: The study objective was to evaluate the midterm results of a technique
      for correction of posterior leaflet prolapse without resection or use of
      artificial chordae. METHODS: From May 2009 to October 2013, 96 patients with
      isolated posterior leaflet prolapse (n=36) or bileaflet prolapse (n=60) with or
      without chordal rupture underwent posterior leaflet repair at the Prince Sultan
      Cardiac Center. The novel Uniscallop ("U") technique was used in 46 patients
      (group U), based only on scallop suture without resection or artificial chordae
      application. A conventional approach (quadrangular or triangular resection, focal
      sliding, artificial chordae) was adopted in the remaining 50 patients (group C).
      In both groups, the annulus was reshaped using a 40- or 50-mm-long band.
      Postoperative echocardiography was performed in all patients after a mean follow
      up of 18+/-13 months in group U and 20+/-9 months in group C. RESULTS: There were
      no early or late deaths. No patients in either group showed systolic anterior
      motion. Both surgical strategies were successful in obtaining a significant
      reduction in mitral regurgitation grade. Left ventricular function was
      maintained, and tricuspid regurgitation grade was reduced overall. Moderate
      mitral regurgitation during follow-up developed in only 1 patient in group C, as
      the result of dehiscence of a plication stitch. CONCLUSIONS: Although the
      rationale for the use of the U technique is different from what is generally
      accepted, the midterm results of this approach are comparable to those obtained
      with more conventional techniques, remaining stable after a mean follow-up of 18
      months.

PMID- 24680393
TI  - Intrapartum detection of Group B streptococci colonization by rapid PCR-test on
      labor ward.
AB  - OBJECTIVE: Group B streptococci (GBS) may lead to early onset neonatal sepsis
      with severe morbidity and mortality of newborns. Intrapartum detection of GBS is
      needed. The objective was to compare a PCR-based test performed in the laboratory
      versus labor ward. STUDY DESIGN: 300 patients were included prospectively. In
      phase I, swabs were analyzed by selective culture and rapid PCR in the
      laboratory. In phase II, swabs were analyzed accordingly, but the PCR test was
      conducted in labor ward. Test performances were analyzed and compared. RESULTS:
      In phase I the rapid PCR test had a sensitivity of 85.71% and a specificity of
      95.9%. The GBS colonization rate was 18.67%. Overall 8.5% of the PCR results were
      invalid. In phase II the PCR test showed a sensitivity of 85.71% and a
      specificity of 95.65%. The GBS colonization rate was 23.3%. Overall 23.5% of
      swabs tested with PCR were invalid. Initiation of specific, short 2-hour training
      for operating personnel in the labor ward reduced the invalid test rate to 13.4%.
      CONCLUSION: The rapid PCR-based test yields adequate results to identify GBS
      colonization when performed in labor ward. In order to reduce the number of
      invalid tests a short training period is needed.

PMID- 24680394
TI  - The role of C-reactive protein measurement as a diagnostic aid in early
      pregnancy.
AB  - OBJECTIVE: To investigate the values of C-reactive protein (CRP) in early
      pregnancy for detection of any abnormality of the conceptus and especially the
      condition of extra-uterine pregnancy (EUP). STUDY DESIGN: In this prospective
      observational study, we established reference values for CRP in early pregnancy.
      Next, we tested whether a single, wide-range CRP measurement could serve as a
      diagnostic tool for abnormal first trimester pregnancy by comparing CRP levels in
      three different pregnancy statuses: viable intrauterine pregnancy (Group A), EUP
      (Group B) and delayed abortion (Group C). RESULTS: CRP levels were significantly
      higher in normal pregnancy (Group A) compared to abnormal pregnancy (Group B+C
      and Group B alone). CRP level was influenced only by the pregnancy status
      (normal, EUP or delayed abortion) and not by age, BMI, hematocrit or gravidity.
      The multiple logistic regression model (adjusted for age, gravidity, gestational
      age, hematocrit and BMI) revealed CRP as being a predictor for normal
      intrauterine pregnancy. CONCLUSION: This study examined the association between
      CRP levels and abnormal first trimester pregnancies. Our results support single
      CRP measurement as a diagnostic tool in early pregnancy.

PMID- 24680395
TI  - Preterm delivery risk factors in singletons born after in vitro fertilization
      procedures.
AB  - OBJECTIVES: Women delivering singletons after in vitro fertilization (IVF)
      procedures have a greater risk of preterm delivery (PD). The aim of our study was
      to analyze PD risk factors and to identify those that could possibly be
      prevented. STUDY DESIGN: In our matched controlled study we analyzed 1127
      singleton deliveries after IVF and transfer of fresh embryos performed at the
      University Medical Center Ljubljana between 1 January 2002 and 31 December 2010.
      For every delivery included in the study group we chose three consecutive
      controls matched by maternal age, parity and maternity hospital. The main outcome
      measure was PD (<37 weeks). Investigated variables were: previous PD (PPD),
      conization, pregestational diabetes mellitus, uterine anomaly, operation on the
      uterus, chronic renal disease, maternal age and parity, and body mass index
      (BMI). Variables investigated within the IVF group were: stimulation protocol,
      laboratory procedure, number of retrieved oocytes and number and quality of
      transferred embryos. RESULTS: The PD rate after IVF was 1.5 times higher than
      after natural conception (11.5% in the IVF group and 7.7% in the control group,
      p<0.001). Conization and chronic renal disease were shown to be significant risk
      factors for PD in both the IVF group and the naturally conceiving controls.
      BMI>30 was an important risk factor only in the IVF group (OR 1.86 (1.06-3.27)
      vs. 1.10 (0.67-1.80)) and PPD only in the controls (OR 1.83 (0.78-4.28) vs. 3.22
      (1.55-6.67)). Among the investigated PD risk factors, an IVF procedure was shown
      to be the fifth most important one. On analyzing parameters of the ovarian
      stimulation and IVF procedure, no PD risk factor was identified. CONCLUSIONS: IVF
      was shown to be a significant risk factor for PD. In the IVF population, BMI
      plays a far more important role in PD than in the fertile population. In our
      research PD reoccurrence in IVF group was less than expected, which could perhaps
      be explained by the surgical correction of gynecological pathology and, where
      necessary, its being combined with cerclage. The investigation of parameters
      related to the IVF procedure did not identify any risk factors for PD.

PMID- 24680397
TI  - Giant invasive basal skull prolactinoma with CSF rhinorrhoea and meningitis.

PMID- 24680396
TI  - A comparison of the miscarriage rate between women with and without polycystic
      ovarian syndrome undergoing IVF treatment.
AB  - OBJECTIVE: To investigate if patients with polycystic ovary syndrome (PCOS) who
      conceived via IVF treatment had a higher miscarriage rate than non-PCOS subjects
      after controlling for several important confounding variables relating to
      pregnancy loss. STUDY DESIGN: A retrospective, observational, cohort study
      including a consecutive series of 564 embryo transfer cycles from PCOS patients
      and 7494 embryo transfer cycles from non-PCOS patients. Only the first pregnancy
      arising from IVF treatment was included for subsequent analysis. None of the
      subjects underwent ovarian diathermy or drilling prior to IVF treatment. Low dose
      (<=1000mg daily), short term (<=3 weeks) metformin therapy was used in 50 of the
      301 PCOS subjects included in the study. RESULTS: After controlling for the
      number of embryo transferred, the type of embryos transferred (fresh or frozen
      thawed), and the stage of embryo development at the time of transfer, women with
      PCOS had a consistently higher biochemical pregnancy rate than women without PCOS
      (fresh single day 3 embryo transfer, 46.7% (7/15) vs. 14.5% (27/186),
      respectively, p<0.05; frozen-thawed single day 3 embryo transfer, 25.9% (7/27)
      vs. 6.1% (11/181), p<0.05; fresh double day 3 embryo transfer, 17.1% (12/70) vs.
      7.6% (95/1256), p<0.05; frozen-thawed double day 3 embryo transfer, 7.9% (15/189)
      vs. 3.4% (66/1968), p<0.05). There was no significant difference in the clinical
      miscarriage rate between the two groups of subjects. CONCLUSION: PCOS patients
      who conceived following IVF treatment had higher biochemical loss than women
      without PCOS, but the clinical miscarriage rate was no different between the two
      groups.

PMID- 24680398
TI  - Effect of SAMMPRIS on endovascular interventions for intracranial
      atherosclerosis.

PMID- 24680399
TI  - [Promoting scientific spirit for a better pediatric research].

PMID- 24680400
TI  - [Guiding development of pediatrics in China, focusing on the frontiel of
      scientific research-make an effort to promote the development of Chinese Journal
      of Pediatrics].

PMID- 24680401
TI  - [Multi-center study of premature thelarche and gynecomastia in Chinese infants
      and toddlers].
AB  - OBJECTIVE: The term "premature thelarche" refers to isolated breast development
      before 8 years of age in female, without any other signs of sexual maturation,
      while "gynecomastia" is the presence of breast tissue in males. This study aimed
      to investigate the prevalence of premature thelarche and gynecomastia in Chinese
      infants and toddlers, identify the potential risk factors, and explore the
      influence of early breast development on physical growth, mental development and
      psychomotor development. METHOD: A total of 1 510 full term and healthy children
      at the age of 0-48 months were sampled by stratified cluster random sampling
      method from 8 provinces from 2011-2012. Weight, height and breast development
      were assessed by senior primary pediatricians, while Bayley Scale of Infant
      Development-I (BSID-I) was used to measure the mental developmental index (MDI)
      and psychomotor developmental index (PDI) for children aged 2-30 months. Social
      demographic Questionnaires were completed by the caregivers. RESULT: The combined
      prevalence of premature thelarche and gynecomastia was 1.6% (23/1 475), girls
      2.2% (15/695), boys 1.0% (8/780), all within 2 years of age. The birth weight,
      feeding patterns in first 4 months, delivery mode, weaning time and social
      economic status were not significantly associated with the breast development.
      However, lower father's education level (OR = 3.632, 95%CI = 1.565-8.432) as well
      as smoking mother (OR = 18.960, 95%CI = 1.590-226.304) were significantly related
      to breast development even after adjusting for potential confounders. Lower
      weight (-0.479 +/- 0.648 vs. 0.005 +/- 0.987, P < 0.05) and height (-0.602 +/-
      1.042 vs. 0.008 +/- 0.986, P < 0.05) Z score were found in breast development
      group, even after adjusting for age, gender and father' education level. Neither
      mental development (t = -0.082, P > 0.05) nor psychomotor development (t = 1.054,
      P > 0.05) was associated with breast development. CONCLUSION: We showed a similar
      prevalence of premature thelarche with the data reported in similar studies
      reported from other countries. Among the 0-48 months old infants and toddlers,
      Father's education level and smoking mother were both related to breast
      development. Breast development was significantly associated with physical
      growth, but had no correlation with the mental or psychomotor development.

PMID- 24680402
TI  - [Relationship between birth weight and elevated blood pressure among children
      aged 6-11 years in China].
AB  - OBJECTIVE: To analyze the relationship between birth weight and elevated blood
      pressure among schoolchildren aged 6-11 years in 8 provinces of China. METHOD: A
      stratified random cluster sampling was used from sampling frame of eight
      provinces in the mainland of China. A total of 18 920 students aged 6-11 years
      eventually participated in this study. Height, weight, waist circumference (WC)
      and blood pressure of all the subjects were measured. Korotkoff I and V were
      recorded as systolic blood pressure (SBP) and diastolic blood pressure (DBP).
      Elevated blood pressure was considered for SBP and/or DBP equal to or above the
      reference sex-, age- and height-specific 95th percentile. Birth weight and family
      history of hypertension were collected by self-administered questionnaire.
      Analysis of variance was used to compare body measure indicators among 3 birth
      weight groups. Multivariate Logistic regression analysis was performed to
      identify the relationship between birth weight, current BMI and elevated blood
      pressure among children. RESULT: The level of height, weight, WC, BMI, SBP and
      DBP were on the rise with the increase of the birth weight groups among boys (P <
      0.05), except for WC among boys aged 6-8 years. The level of height, weight, WC,
      BMI and DBP showed a trend of escalation among girls (P < 0.05). But, SBP among 3
      birth weight groups in girls was not significantly different (P = 0.099). After
      adjusting for age and family history of hypertension, compared with the normal
      birth weight group, the odds ratio and 95%CI of having elevated blood pressure
      among boys and girls in high birth weight group were 1.23 (1.06-1.43) and 0.89
      (0.71-1.10), respectively; and the ORs(95%CI) were 1.06 (0.90-1.24) for boys and
      0.73 (0.58-0.91) for girls after adjusting for age, family history of
      hypertension and current BMI of students. The relative risk of elevated blood
      pressure for boys and girls in low birth weight group were not significantly
      different as compared with normal birth weight group. CONCLUSION: Current BMI but
      not birth weight was found to be a strong determinant of elevated blood pressure
      among children aged 6-11 years in China.

PMID- 24680403
TI  - [Epidemiological survey of asthma in children aged 0-14 years in seven districts
      of Shanghai].
AB  - OBJECTIVE: To find out the prevalence of childhood (0-14 years old) asthma in
      Shanghai, to investigate the clinical characteristics and risk factors of asthma,
      and to assess the influence of asthma on patients and their families. METHOD:
      From September to December in 2010, 7 districts of Shanghai were selected by
      clustered sampling, totally 13 500 children aged 0-14 years were included in this
      survey. The investigation included questionnaires to parents and field survey,
      according to the information from questionnaires, the prevalence of asthma and
      clinical characteristics were analyzed, and the risk factors of asthma were
      evaluated by logistic regression analysis. RESULT: Totally 13 179 questionnaires
      were available, the response rate was 97.62%. Among them 998 (7.57%) children
      were diagnosed as asthma (including 895 cases of typical asthma and 103 cases of
      cough variant asthma), of whom 766 (76.75%) cases had asthmatic symptoms in the
      past 2 years, the current two year prevalence of asthma was 5.81%. The prevalence
      in boys was 8.48% (598/7 054) which was much higher than that in girls (6.53%,
      400/6 125, chi(2) = 17.75, P < 0.001). The children aged 3-8 years had higher
      prevalence (10.46%), and more than half of the children (545 cases, 54.61%) had
      the first onset before 3 years of age. Respiratory tract infection was the most
      common trigger for the development of asthma (838 cases, 84.97%). Male (OR =
      0.25, 95%CI: 0.12-0.45) , genetic factors (OR = 2.65, 95%CI: 1.27-5.55) ,
      personal history of allergic diseases (OR = 9.57, 95%CI: 4.59-19.97) , and
      antibiotics exposure in early life (OR = 0.61, 95%CI: 0.49-0.83) would increase
      the risk of asthma onset. Among asthmatic children, 463 (46.39%) cases had been
      treated with inhaled corticosteroids, and 740 (74.15%) cases had been treated
      with bronchodilator. In 501 cases of school-age children's attendance time had
      been influenced because of their disease; 2.51% of parents could not work
      normally. CONCLUSION: There has been a significantly increasing trend of asthma
      prevalence during the past ten years, sex, family history of allergic diseases,
      personal history of allergic diseases and antibiotics exposure in early life are
      risk factors which would influence on the asthma onset. Education on and
      management of asthma are essential for asthma prevention.

PMID- 24680404
TI  - [Magnetic resonance imaging of premature infants with punctate white matter
      damage and short-term neurodevelopmental outcome].
AB  - OBJECTIVE: To investigate the early diagnosis with MRI changes, MRI types and
      short-term neurodevelopmental outcome of preterm infants with punctate white
      matter damage (PWMD). METHOD: There were 44 preterm infants with PWMD (group A)
      from March 2009 to August 2010 at the neonatal ward of Shengjing Hospital of
      China Medical University, according to the number, shape and distribution of the
      lesions, group A was divided into dot injury group (A1), clusters group (A2) and
      linear group (A3), the first MRI and DWI scan of all cases were within 14 days
      after birth, and 17 subjects received re-examination with the MRI in the
      hospital. Twenty preterm infants with normal MRI (group B) received the follow
      up, according to the age, 20 normal full-term infants were selected (group C) as
      the control group using paired design. Mental development index (MDI) and
      psychomotor development index (PDI) were determined using Bayley scales of infant
      development-II. RESULT: First MRI scan:in 44 infants with PWMD, group A1, A2, A3
      separately had, 10, and 9 infants. MRI follow up in 17 cases showed that in 4
      cases of A1 group the dot lesions disappeared; in 3 of 4 cases in clusters group
      who received re-examination, the lesions disappeared, 1 case had periventricular
      leukomalacia (PVL); in 5 of the 9 cases who had re-examination in linear group
      the lesions disappeared, while in 4 cases the lesions evolved into PVL. MDI and
      PDI: Group A [MDI (102.9 +/- 15.5) , PDI (107.7 +/- 17.5) ] was lower than that
      of group B[MDI (114.0 +/- 13.1) , PDI (120.8 +/- 9.4) ], group C [MDI (114.2 +/-
      12.2) , PDI (119.5 +/- 10.7) ] (P < 0.05) . There were no significant differences
      between group B and group C. Group A1 [MDI (112.2 +/- 8.1) , PDI (116.4 +/- 8.5)
      ] had no significant differences compared with group B and group C. Group A2 [MDI
      (100.8 +/- 12.5) , PDI (105.0 +/- 12.1) ] showed significantly reduced values
      compared with group B, Group C, Group A1 (P < 0.05) ,Group A3 [MDI (75.8 +/-
      11.6) , PDI (79.1 +/- 16.2) ] had lower values than group B, Group C, Group A1,
      and Group A2 (P < 0.05) . CONCLUSION: Premature infants with PWMD mainly showed
      dot-like and clustered injury that are easy to be absorbed and disappear, but the
      linear lesions are likely to evolve into PVL. In addition, the cluster-like and
      linear injury have an influence on short-term cognition and motion development,
      especially the outcome of linear injury was the worst.

PMID- 24680405
TI  - [Relationship between expression of microRNA and inflammatory cytokines plasma
      level in pediatric patients with sepsis].
AB  - OBJECTIVE: Sepsis is the major cause of death in pediatric intensive care unit
      (PICU). The clinical manifestations of early sepsis is very similar to systemic
      inflammatory response syndrome (SIRS) caused by non-infectious reason. This study
      aimed to investigate the expression of miRNA and inflammatory cytokines in plasma
      in pediatric sepsis patients and its clinical significance. METHOD: Forty
      children with sepsis seen in Shenzhen children's hospital PICU from April 2012 to
      March 2013 were enrolled in this study, the median age was 0.75 (0.52, 1.90)
      years; 27 were males and 13 females, of whom 16 had severe sepsis. We selected 20
      postsurgical patients with SIRS and 15 healthy children as a control group. The
      expression levels of plasma miR-21, miR-125b, miR-132, miR-146a, miR-155 and miR
      223 were detected by real-time quantitative PCR (qRT-PCR). The predictive value
      of miRNA, PCT and CRP for sepsis were evaluated by Receiver operating
      characteristic curve (ROC). TNF-alpha and IL-10 levels in plasma detected by
      Cytometric Beads Array (CBA). Quantitative data of normal distribution was
      compared with ANOVA among the three groups and LSD-t test between two groups. To
      non-normal distribution of data, multiple comparisons among three groups were
      conducted by Kruskal-Wallis H test and differences between two groups were
      assessed by Mann-Whitney U test for post hoc analysis. RESULT: There were no
      significant differences between the age and gender of each group. Expression of
      miR-21, miR-125b, miR-132 and miR-155 in plasma had no significant difference in
      each group (all P > 0.05). MiR-146a and miR-223 levels in sepsis were upregulated
      compared with SIRS group and control group [(5.7 +/- 3.5)*10(-5) vs. (2.4 +/-
      1.6)*10(-5) and (2.6 +/- 1.2)*10(-5), (12.5 +/- 7.7)*10(-4) vs. (8.3 +/- 3.4)*10(
      4) and (5.3 +/- 2.2)*10(-4), all P < 0.01], expression levels of miR-223 in SIRS
      increased as compared to control group (P < 0.01). MiR-146a levels in severe
      sepsis were higher than those of the general sepsis [ (7.1 +/- 3.3)*10(-5) vs.
      (4.6 +/- 2.6)*10(-5), P < 0.01]. CRP and PCT levels are all higher in sepsis and
      SIRS groups than control group (all P < 0.01). The area under ROC curve (AUC) of
      miR-146a, miR-223, PCT and CRP to predict sepsis were 0.815 (95%CI: 0.708-0.922),
      0.678(95%CI: 0.537-0.818), 0.706 (95%CI: 0.571-0.842) and 0.588 (95%CI: 0.427
      0.748). Expression levels of IL-10 and IL-10/TNF-alpha in sepsis were upregulated
      compared with and SIRS group and the control group (all P < 0.01). There was a
      positive correlation between miR-146a, miR-223 and IL-10 and IL-10/TNF-alpha (r =
      0.545, 0.305, 0.562, 0.373, all P < 0.01). CONCLUSION: The expression levels of
      miR-146a and miR-223 in plasma in pediatric patients with sepsis was
      significantly upregulated, and had a positive correlation with IL-10 and IL
      10/TNF-alpha, which may be used as early diagnostic markers and can reflect the
      severity of condition to a certain degree.

PMID- 24680406
TI  - [Application of three kinds of non-invasive positive pressure ventilation as a
      primary mode of ventilation in premature infants with respiratory distress
      syndrome: a randomized controlled trial].
AB  - OBJECTIVE: Non-invasive positive pressure ventilation has increasingly been
      chosen as the primary ventilation mode in respiratory distress syndrome (RDS) in
      preterm infants. In order to further understand the application of various non
      invasive positive pressure ventilation modes, we compared the advantages and
      disadvantages of three modes as a primary mode of ventilation in premature
      infants with RDS. METHOD: From December 2011 to March 2013, 107 preterm infants
      with RDS who received intubation-pulmonary surfactant (PS) -extubation in our
      NICU were randomly divided (by means of random number table) into three groups
      based on the primary mode of ventilation: nasal continuous positive airway
      pressure [NCPAP, n = 39, male/female ratio was 27/12, mean gestational age (GA)
      was (32.0 +/- 2.1)weeks, mean birth weight (BW) was (1752 +/- 457)g], bi-level
      positive airway pressure [BiPAP, n = 35, male/female ratio was 25/10, GA was
      (31.4 +/- 2.0) weeks, BW was (1530 +/- 318) g], and synchronized bi-level
      positive airway pressure [SBiPAP, n = 33, male/female rate was 25/8, GA was (31.5
      +/- 2.2) weeks, BW was (1622 +/- 447) g]. Ventilation settings including FiO(2)
      were adjusted according to transcutaneous SPO(2) monitoring or blood gas
      analysis. Various settings and adverse events were recorded as well. The main
      parameter was the FiO(2) at 24 h post-positive-pressure ventilation. Statistical
      analyses were performed using chi(2) test, rank sum test, one-way analysis of
      variance for least-significant difference value, paired-sample t-test, two
      related sample Wilcoxon signed rank sum test and Logistic regression. RESULT: The
      PaCO(2) (mmHg, 1 mmHg = 0.133 kPa), oxygen index (OI) at 12-24 h, and FiO(2) at
      24 h post-ventilation in BiPAP and SBiPAP groups were lower than that in NCPAP
      groups with significant difference (44 +/- 9 and 45 +/- 9 vs. 50 +/- 9, 2.76 +/-
      0.96 and 2.79 +/- 0.60 vs. 3.24 +/- 0.72, 0.34 +/- 0.10 and 0.35 +/- 0.07 vs.
      0.39 +/- 0.07; F = 4.456, 5.146 and 4.123; P = 0.014, 0.007 and 0.019,
      respectively). There was no significant difference between BiPAP and SBiPAP
      groups. There was no significant difference among three groups (all P > 0.05) in
      the following events: respiratory index (RI) at 12-24 h post-ventilation,
      abdominal distension, period of non-invasive ventilation, ratio of intubation for
      invasive ventilation if failed noninvasive ventilation, air-leak syndrome,
      neonatal necrotizing enterocolitis, periventricular-intraventricular haemorrhage,
      bronchopulmonary dysplasia, retinopathy of prematurity, mortality rate after 36 h
      of age or rate of abandon for discharge. The independent risk factors for failure
      of non-invasive positive pressure ventilation were gender, gestational age,
      antepartum steroid at 24 h before birth to 7 d, and birth weight, with the OR
      (95% confidence interval) being 14.120 (1.135, 175.662), 2.862 (1.479, 5.535),
      61.084 (3.115, 1 198.031), and 8.306 (1.488, 46.383), respectively. CONCLUSION:
      As the primary mode of ventilation in premature infants with RDS, both BiPAP and
      SBiPAP are more beneficial than NCPAP in improving oxygenation and reducing CO(2)
      retention without increasing the incidence of adverse events.

PMID- 24680407
TI  - [Clinical application of magnetic resonance imaging in congenital anorectal
      malformation].
AB  - OBJECTIVE: To investigate the clinical value of MRI examination in congenital
      anorectal malformation (CARM). METHOD: Forty-four cases with operatively proved
      anorectal malformation from May 2008 to May 2012 in the authors' hospital were
      reviewed. Of the 44 cases, 25 were males and 19 females, their age ranged from 1
      day to 2 years. MRI was performed in all patients. RESULT: Of all 44 cases, 15
      cases had high imperforate anus (34%), rectum blind end were above PC line, the
      distance of rectum blind end and anus nest was (29.12 +/- 2.35) mm; 8 cases had
      median imperforate anus (18%), rectum blind ends were near PC line, the distance
      of rectum blind end and anus nest was (18.98 +/- 2.21) mm; 21 cases had low
      imperforate anus (48%), rectum blind ends were below PC line, the distance of
      rectum blind end and anus nest was (7.54 +/- 1.08) mm. Twenty-five cases with
      fistula in 44 cases were confirmed by rectal angiography and surgery, accounting
      for 57%. In 13 cases with fistula, the lesion could be clearly demonstrated on
      MRI, in the remaining 12 cases with fistula, the lesion could not be visualized
      clearly or no image development occurred on MRI. Of all 44 cases, 1 case had
      tethered cord with filum terminale lipoma, 1 case had tethered cord, 2 cases had
      syringomyelia, 1 case had right kidney agenesis, 1 case had hydrocele. In 44
      cases of multi-planar MRI imaging could clearly show the perianal muscles
      developmental situation, 36 cases had perianal muscles dysplasia, amd showed
      levator ani muscle, puborectalis and anal sphincter asymmetry, muscle belly slim.
      CONCLUSION: MRI examination has a high clinical value in CARM diagnosis, can help
      accurately judge the anal atresia type, display the presence and running of most
      of the fistula, and diagnose perianal muscle development and other systems
      malformations, finally provide a reliable diagnostic basis for surgical program
      and prognostic assessment.

PMID- 24680408
TI  - [Clinical characteristics and antimicrobial resistance of invasive group A beta
      hemolytic streptococcus infection in children].
AB  - OBJECTIVE: Group A beta-hemolytic streptococcus (GAS) or Streptococcus pyogenes
      may be encountered in diverse clinical situations in children. A rising incidence
      of invasive group A streptococcus (IGAS) infections has been noted in children in
      the past three decades. The aim of this study was to summarize the clinical
      characteristics and antimicrobial resistance of IGAS in children, and to raise
      the level of diagnosis and treatment of this infection. METHOD: The clinical data
      from 19 cases of IGAS younger than 14 years old seen from January 2004 to
      December 2011 treated in the authors' hospital were analyzed. IGAS infections are
      defined as the isolation of GAS from a normally sterile site in patients. RESULT:
      The 19 cases were identified as IGAS infections, among whom 15 were male and 4
      were female, and the ratio of them was 3.75. The age ranged from 1 day to 14
      years, with a median age of 4 years. The course of disease was 4 h-10 days. The
      average length of stay was 12.2 days. In 13 cases the episodes of the infection
      occurred in winter and spring. In 18 cases the infection was community-acquired.
      Overall, 10 cases had neck or foot dorsum abscess, four cases had purulent
      peritonitis, and 3 cases were diagnosed as streptococcal toxic shock syndrome
      (STSS) complicated with empyema, pyopneumothorax occurred in 1 case and neonatal
      septicemia in another. Three cases had an underlying disease, including 2 cases
      wounded in a car accident and 1 case of congenital esophageal atresia and
      tracheoesophageal fistula. Before the isolation of GAS, 5 cases had stayed in
      ICUs, the length of ICU stay was 1-32 days, 4 cases had received intubation and
      mechanical ventilation, the ventilation time was 8 h-24 days, 2 cases had
      received major surgery; 5 cases had other pathogen coinfection, including 4 cases
      of abdominal pus at the same time and Escherichia coli was isolated, and 1 case
      had parainfluenza virus type I coinfection. Peripheral blood leucocyte increased
      in 18 cases, one case dropped off. The C-reactive protein (CRP) levels increased
      in all patients, including 16 cases who had 14-160 mg/L, 3 cases had levels
      higher than 160 mg/L. Twenty strains of GAS were isolated from 19 cases' sterile
      sites, of them 10 strains were isolated from abscess, 4 strains were isolated
      from blood and another 4 from ascites. Two strains were from the same patient at
      different times of pleural effusion. All 20 strains displayed a full
      susceptibility to cefazolin, levofloxacin and vancomycin, and the rates of
      resistance to both cefotaxime and penicillin were 10.0%. The rates of resistance
      to erythromycin and clindamycin were 55.0% and 70.0% respectively. Among the
      patients 3 cases were cured, 14 cases improved, and 2 cases died, of whom 1 case
      died of STSS secondary to multiple organ dysfunction, 1 case died of basic
      disease secondary to multiple organ dysfunction. CONCLUSION: Skin and soft
      tissues were the most common IGAS infection sites in children, and IGAS infection
      also can lead to serious STSS and even can be life threatening. Penicillin and
      cephalosporin are still sensitive for children IGAS infections.

PMID- 24680409
TI  - [Clinical investigation of formula feeding in extremely low birth weight
      infants].
AB  - OBJECTIVE: To explore the relationship between gastric retention and full enteral
      feeding during the course of feeding in extremely low birth weight (ELBW, birth
      weight <1 000 g) infants. METHOD: A total of 43 ELBW infants were fed with
      formula according to the strategy for premature infants feeding of Canadian
      Society of Neonatology. The information such as gastric retention, the time they
      finish full enteral feeding and sucking spontaneously and complication were
      recorded. These infants had transition to full enteral feeding step by step since
      initiating formula feeding on the second day of life. The volume of gastric
      retention and the duration of gastric retention was analyzed with the time of
      attaining full enteral feeding and sucking spontaneously by linear regression.
      RESULT: Forty-one infants finished the course, the remaining 2 infants got
      necrotizing enterocolitis (NEC) and were rescued by surgery. The incidence was
      4.6%. In 18 infants full enteral feeding could not be initiated successfully on
      the second day of life, the incidence was 43.9%. The peak duration of gastric
      retention was the first week of feeding. The average time of attaining enteral
      feeding was (26.71 +/- 12.24) days. The proportion of different residual contents
      was simlar, the major content was milky content after 3 weeks of feeding. The
      gastric retention time had a significant effect of on the time of attaining full
      enteral feeding (beta = 1.045, P = 0.001) and sucking well (beta = 0.787, P =
      0.034) . CONCLUSION: The course of formula feeding ELBW infants to attaining full
      enteral feeding was a long period, in the early stage of formula feeding the
      occurrence of gastric retention was high; the amount of formula during the first
      week of feeding should be slowly increased as compared to the second week; the
      present strategy and aggressive strategy should be done 2 weeks later. The time
      of attaining full enteral feeding can be predicted by the duration of gastric
      retention.

PMID- 24680411
TI  - [A Chinese patient with glycogen storage disease type Ib caused by mutations in
      the glucose-6-phosphate translocase gene].

PMID- 24680410
TI  - [Case report: neonatal Prader-Willi syndrome].

PMID- 24680412
TI  - [Two pairs of monozygotic twins with concordant acute lymphoblastic leukemia:
      case report].

PMID- 24680413
TI  - [Neonatal cholestasis associated with fetal paroxysmal supraventricular
      tachycardia].

PMID- 24680414
TI  - [A case of neonatal incomplete Kawasaki disease complicated with aseptic
      meningitis].

PMID- 24680415
TI  - [Advantages and limitations of fetal cardiac intervention].

PMID- 24680416
TI  - [The progress in molecular genetics and clinical features of arthrogryposis-renal
      tubular dysfunction-cholestasis syndrome].

PMID- 24680417
TI  - [Case 136th--intermittent fever for over 20 days and coughing for 2 days].

PMID- 24680418
TI  - [A brief introduction to the 2013 annual conference of Pediatric Academic
      Societies in the United States].

PMID- 24680419
TI  - Immune thrombocytopenic purpura: major progress in knowledge of the
      pathophysiology and the therapeutic strategy, but still a lot of issues.

PMID- 24680420
TI  - [Adrenal gland in 2014].

PMID- 24680421
TI  - Warm autoimmune hemolytic anemia: advances in pathophysiology and treatment.
AB  - Autoimmune hemolytic anemia due to warm antibodies (wAIHA) accounts for
      approximately 70% to 80% of all AIHAs in adults. The pathogenesis of wAIHA is a
      complex multistep process, the last step of which being the abnormal production
      of auto-antibodies directed towards red blood cells' membrane antigens. The
      recent advances in the understanding of the underlying mechanisms leading to the
      breakdown of self-tolerance in wAIHA, mainly thanks to the study of animal models
      are discussed in this review. Treatment of wAIHA has long been empirical and
      mainly based on corticosteroids. In the last decade however, the efficacy of
      rituximab as second-line treatment has been demonstrated first in retrospective
      and more recently throughout prospective studies. Based on these advances, an
      algorithm for the management of primary adult's wAIHA is proposed in this review.

PMID- 24680422
TI  - Thrombopoietic agents: there is still much to learn.
AB  - Thrombopoietic growth factors have had an interesting development path. Many
      studies were done with the first generation agents and this has defined the
      current way that the second generation agents are used. While the first
      generation agents were not surprisingly targeted at chemotherapy-induced
      thrombocytopenia, the second generation ones have been initially developed in
      ITP. Surprisingly, the thrombopoietic agents have not been as simple to work with
      as would have been anticipated in that the relationship of treatment to the
      platelet count, what to expect, in what patient, and with which underlying cause
      of thrombocytopenia has not nearly been as straight forward as it could be.
      Rather than being an "encyclopedic" review, this manuscript is intended to
      provide a state of the art description of what we do and do not know in regard to
      important questions about usage of these still novel agents. 

PMID- 24680423
TI  - Autoimmune neutropenia.
AB  - Autoimmune neutropenia (AIN) is a rare entity caused by antibodies directed
      against neutrophil-specific antigens. It includes primary and secondary
      autoimmune neutropenia. Acute autoimmune neutropenia can be related to drug
      induced mechanism or viral infections. Chronic autoimmune neutropenias occur in
      the context of autoimmune diseases, hematological malignancies, such as large
      granular lymphocyte leukemia, primary immune deficiency syndromes or solid
      tumors. The therapeutic management depends on the etiology. Granulocyte growth
      factor is the main therapeutic option, raising the question of their long-term
      utilization safety. Corticosteroids or immunosuppressive therapy are indicated in
      infection-related AIN or in case of symptomatic autoimmune disease or LGL
      leukemia. 

PMID- 24680424
TI  - Extensive shape shifting underlies functional versatility of arrestins.
AB  - Among four vertebrate arrestins, only two are ubiquitously expressed. Arrestins
      specifically bind active phosphorylated G protein-coupled receptors (GPCRs),
      thereby precluding further G protein activation. Recent discoveries suggest that
      the formation of the arrestin-receptor complex initiates the second round of
      signaling with comparable biological importance. Despite having virtually no
      recognizable sequence motifs known to mediate protein-protein interactions,
      arrestins bind a surprising variety of signaling proteins with mind-boggling
      range of functional consequences. High conformational flexibility allows
      arrestins to show many distinct 'faces' to the world, which allows these
      relatively small ~45kDa proteins to bind various partners under different
      physiological conditions, organizing multi-protein signaling complexes and
      localizing them to distinct subcellular compartments. 

PMID- 24680425
TI  - Role of G protein-coupled receptor kinases in cell migration.
AB  - G protein-coupled receptor kinases (GRKs) are emerging as important integrative
      nodes in cell migration processes. Recent evidence links GRKs (particularly the
      GRK2 isoform) to the complex modulation of diverse aspects of cell motility. In
      addition to its well-established role in the desensitization of G protein-coupled
      receptors involved in chemotaxis, GRK2 can play an effector role in the
      organization of actin and microtubule networks and in adhesion dynamics, by means
      of novel substrates and transient interacting partners, such as the GIT1 scaffold
      or the cytoplasmic alpha-tubulin deacetylase histone deacetylase 6 (HDAC6). The
      overall effect of altering GRK levels or activity on chemotaxis would depend on
      how such different roles are integrated in a given cell type and physiological
      context, and may have relevant implications in inflammatory diseases or cancer
      progression. 

PMID- 24680426
TI  - Recent developments in biased agonism.
AB  - The classic paradigm of G protein-coupled receptor (GPCR) activation was based on
      the understanding that agonist binding to a receptor induces or stabilizes a
      conformational change to an 'active' conformation. In the past decade, however,
      it has been appreciated that ligands can induce distinct 'active' receptor
      conformations with unique downstream functional signaling profiles. Building on
      the initial recognition of the existence of such 'biased ligands', recent years
      have witnessed significant developments in several areas of GPCR biology. These
      include increased understanding of structural and biophysical mechanisms
      underlying biased agonism, improvements in characterization and quantification of
      ligand efficacy, as well as clinical development of these novel ligands. Here we
      review recent major developments in these areas over the past several years. 

PMID- 24680427
TI  - Structural insights into G protein-coupled receptor kinase function.
AB  - The atomic structure of a protein can greatly advance our understanding of
      molecular recognition and catalysis, properties of fundamental importance in
      signal transduction. However, a single structure is incapable of fully describing
      how a protein functions, particularly when allostery is involved. Recent advances
      in the structure and function of G protein-coupled receptor (GPCR) kinases (GRKs)
      have concentrated on the mechanism of their inhibition by small and large
      molecules. These studies have generated a wealth of new information on the
      conformational flexibility of these enzymes, which opens new avenues for the
      development of selective chemical probes and provides deeper insights into the
      molecular basis for activation of these enzymes by GPCRs and phospholipids. 

PMID- 24680429
TI  - Atypical regulation of G protein-coupled receptor intracellular trafficking by
      ubiquitination.
AB  - G protein-coupled receptor (GPCR) signaling is precisely regulated. After
      activation, GPCRs are desensitized, internalized and either recycled to the cell
      surface or sorted to lysosomes for degradation. The main route for GPCR lysosomal
      sorting requires ubiquitination and the endosomal-sorting complex required for
      transport (ESCRT). Four distinct ESCRT adaptor protein complexes act sequentially
      to bind and sort ubiquitinated cargo to lysosomes. Several studies now indicate
      that alternate pathways exist for GPCR lysosomal sorting that require only some
      components of the ESCRT and autophagy machinery. While direct GPCR ubiquitination
      is not required for alternate lysosomal sorting, new evidence suggests that
      ubiquitin may function indirectly to modulate adaptor protein activity. Here, we
      discuss the atypical regulation of GPCR lysosomal sorting by ubiquitination. 

PMID- 24680430
TI  - Tuning up the right signal: chemical and genetic approaches to study GPCR
      functions.
AB  - The G protein-coupled receptor (GPCR) family is among the most druggable families
      in the human proteome. GPCRs are involved in most physiological processes, and
      our ability to modulate their activity is a hallmark of modern pharmacology. The
      means by which the activity of GPCRs can be modulated have been expanded by
      emerging data and concepts in pharmacology, which has created new strategies for
      their control. These new approaches will lead to the generation of more potent,
      selective, and efficient pharmaceutics, while reducing inappropriate actions and
      adverse effects. Herein, we review and comment on some recent advances in
      chemical and genetic approaches to the profiling of GPCR function, as well as the
      validation of orphan GPCRs as potential therapeutic targets using engineered
      receptors. 

PMID- 24680428
TI  - Structural approaches to understanding retinal proteins needed for vision.
AB  - The past decade has witnessed an impressive expansion of our knowledge of retinal
      photoreceptor signal transduction and the regulation of the visual cycle required
      for normal eyesight. Progress in human genetics and next generation sequencing
      technologies have revealed the complexity behind many inherited retinal diseases.
      Structural studies have markedly increased our understanding of the visual
      process. Moreover, technical innovations and improved methodologies in
      proteomics, macromolecular crystallization and high resolution imaging at
      different levels set the scene for even greater advances. Pharmacology combined
      with structural biology of membrane proteins holds great promise for developing
      innovative accessible therapies for millions robbed of their sight or progressing
      toward blindness. 

PMID- 24680431
TI  - Integrated approaches to understanding antipsychotic drug action at GPCRs.
AB  - The G-protein coupled receptor (GPCR) family of genes represents one of the
      largest druggable families of genes in the human genome. This is evident by the
      fact that approximately 30% of currently marketed drugs target GPCRs. However,
      many of these drugs are limited in their clinical potential as they are
      associated with debilitating side effects-a consequence of our incomplete
      understanding of their pharmacology and the signaling pathways regulated by
      GPCRs. Because of the limited range of tools available to resolve these issues,
      integrated approaches are required to fully understand the pharmacological action
      of drugs and the biochemical repertoire regulated by GPCRs. In this review we
      will focus on the action of antipsychotic drugs on certain monoamine GPCRs in the
      central nervous system (CNS) and the approaches being developed to elucidate
      their distinct pharmacology. 

PMID- 24680432
TI  - Role of beta-arrestins and arrestin domain-containing proteins in G protein
      coupled receptor trafficking.
AB  - The arrestin clan can now be broadly divided into three structurally similar
      subgroups: the originally identified arrestins (visual and beta-arrestins), the
      alpha-arrestins and a group of Vps26-related proteins. The visual and beta
      arrestins selectively bind to agonist-occupied phosphorylated G protein-coupled
      receptors (GPCRs) and inhibit GPCR coupling to heterotrimeric G proteins while
      the beta-arrestins also function as adaptor proteins to regulate GPCR trafficking
      and G protein-independent signaling. The alpha-arrestins have also recently been
      implicated in regulating GPCR trafficking while Vps26 regulates retrograde
      trafficking. In this review, we provide an overview of the alpha-arrestins and
      beta-arrestins with a focus on our current understanding of how these adaptor
      proteins regulate GPCR trafficking. 

PMID- 24680434
TI  - Functional and structural perspectives on allosteric modulation of GPCRs.
AB  - Traditionally, optimizing lead molecule interactions with the orthosteric site
      has been viewed as the best means for attaining selectivity at G protein-coupled
      receptors (GPCRs), but GPCRs possess spatially distinct allosteric sites that can
      also modulate receptor activity. Allosteric sites offer a greater potential for
      receptor subtype selectivity, the ability to fine-tune physiological responses,
      and the ability to engender signal pathway bias. The detection and quantification
      of allosteric drug candidates remain an ongoing challenge, but the development of
      novel analytical approaches for quantifying allostery is enriching structure
      activity and structure-function studies of the phenomenon. Very recent
      breakthroughs in both structural and computational biology of GPCRs are also
      beginning to unravel the mechanistic basis of allosteric modulation at the
      molecular level. 

PMID- 24680433
TI  - Endocytic trafficking of chemokine receptors.
AB  - Chemokine receptors belong to the super family of G protein-coupled receptors
      (GPCRs). The cognate ligands for chemokine receptors are small circulating
      proteins known as chemokines. Upon binding to their cognate chemokines, receptors
      are rapidly desensitized, internalized onto early endosomes and sorted either
      into a recycling pathway or degradative pathway. Chemokine receptor trafficking
      is essential because it limits the magnitude and duration of signaling by
      removing receptors from the cell surface thereby limiting access to their
      ligands, but it also delivers bound chemokines to lysosomes for degradation.
      Receptor sorting into the recycling pathway contributes to resensitization of
      receptor signaling, whereas sorting into the degradative pathway leads to long
      term attenuation of signaling. Recent studies have revealed some key information
      regarding the molecular determinants mediating chemokine receptor internalization
      and have shed light on the mechanisms dictating sorting into either the recycling
      or degradative pathways. Here I discuss our current understanding of the
      mechanisms mediating chemokine receptor trafficking with a focus primarily on
      recent findings for the chemokine receptor CXCR4. 

PMID- 24680435
TI  - Functional selectivity of GPCR signaling in animals.
AB  - At one time, G protein-coupled receptors were envisioned to simply relay either
      inhibitory or stimulatory binary signals through engaging particular G proteins.
      These receptors are now viewed as complex, multidimensional triggers of a variety
      of potential signaling cascades. This review will showcase current attempts to
      elucidate biased signaling and functional selectivity in tissues and organs as
      well as in the whole animal. In addition, it will emphasize the challenges that
      are inherent in attributing bias in a living system as well as offer opinions as
      to the manner in which these problems may be approached. 

PMID- 24680436
TI  - GPCR signaling along the endocytic pathway.
AB  - Many G protein-coupled receptors (GPCRs) internalize after agonist-induced
      activation. While endocytosis has long been associated with homeostatic
      attenuation of cellular responsiveness, accumulating evidence from study of a
      wide range of eukaryotes reveals that the endocytic pathway also contributes to
      generating receptor-initiated signals themselves. Here we review recent progress
      in this area, discussing primarily but not exclusively GPCR signaling in
      mammalian cells. 

PMID- 24680437
TI  - Employing novel animal models in the design of clinically efficacious GPCR
      ligands.
AB  - The headline success of targeting GPCRs in human diseases has masked the fact
      that many GPCR drug discovery programmes fail. This is despite a substantial
      increase in our understanding of GPCR pharmacology that has provided an array of
      ligands that target both orthosteric and allosteric sites as well as ligands that
      show stimulus bias. From this plethora of pharmacological possibilities, can we
      design ligand properties that would deliver maximal clinical efficacy with lowest
      toxicity? This may be achieved through animal models that both validate a
      particular GPCR as a target as well as revealing the signalling mechanisms that
      underlie receptor-mediated physiological and clinical responses. In this article,
      we examine recent novel transgenic models being employed to address this issue. 

PMID- 24680438
TI  - Expert witness testimony in urology malpractice litigation.
AB  - OBJECTIVE: To evaluate the credentials of urologists choosing to testify as
      expert witnesses. As health care reform has become an increasingly important
      topic in national debate, medical malpractice and related issues have come to the
      forefront of topics for discussion by the medical community. Physicians are often
      recruited to testify as expert witnesses in malpractice cases. Defining what
      constitutes an expert in this setting has been an area of controversy. METHODS:
      The Westlaw legal database was searched for medical malpractice litigation. Data
      regarding number of years of experience and practice setting were obtained for
      urologists using private practice and hospital listings, academic faculty
      profiles, and state medical licensing databases. Scholarly impact, as measured by
      the h-index, was calculated by the Scopus database. RESULTS: Plaintiff expert
      witnesses were found to have slightly more years of experience vs defendant
      expert witnesses (35.7 vs 32.2 years, P = .01), but had a lower h-index (6.8 vs
      10.2, P = .03), were less likely to practice in the academic setting (39% vs 60%,
      P = .001), and were more likely to testify multiple times. CONCLUSION: Urologists
      testifying for plaintiffs and defendants both had over 30 years of experience on
      average, with those in the latter having slightly less experience. Defendant
      witnesses, however, had greater scholarly impact and were more likely to practice
      in an academic setting. Organizations such as the American Urological Association
      may wish to re-evaluate guidelines on expert witness testimony, particularly
      regarding those who testify frequently.

PMID- 24680439
TI  - Reply: To PMID 24680438.

PMID- 24680440
TI  - Editorial comment.

PMID- 24680441
TI  - Use of outpatient parenteral antimicrobial therapy for transrectal ultrasound
      guided prostate biopsy prophylaxis in the setting of community-associated
      multidrug-resistant Escherichia coli rectal colonization.
AB  - OBJECTIVE: To study the use of ertapenem delivered in an outpatient parenteral
      antimicrobial therapy (OPAT) hospital-based unit setting for targeted transrectal
      ultrasound-guided prostate biopsy (TRUSPBx) prophylaxis in the setting of
      multidrug-resistant (MDR) Escherichia coli rectal colonization. E coli is the
      pathogen most commonly associated with post-TRUSPBx complications, and there is
      increasing prevalence of community-associated MDR E coli. METHODS: Prospective
      data analysis of all patients admitted to the OPAT unit for administration of
      intravenous antibiotics for prophylaxis for TRUSPBx over 18-month period was
      performed. Patients had identification of MDR E coli in rectal swab cultures
      and/or intolerance to available oral agents. Microbiologic data and tolerability
      of administered antibiotics and outcome after TRUSPBx were tabulated. RESULTS:
      Nine patients (median age 74 years) were referred because of antibiotic-resistant
      E coli from rectal swabs (all fluoroquinolone resistant, 7 MDR). All patients
      received ertapenem 1 g intravenously 1 day before TRUSPBx and the day of the
      procedure before TRUSPBx. None of the patients experienced infectious
      complications immediately after TRUSPBx or several weeks or months later, and no
      patient was lost to urologic follow-up. CONCLUSION: Increasing worldwide reports
      of prostatitis, urinary tract infections, and septicemia after TRUSPBx because of
      MDR E coli suggest rectal screening before procedure may be useful in decreasing
      complications. Targeted prophylaxis in these instances is necessary. Although
      carbapenems are used for treatment, they are not routinely used for prophylaxis.
      We report successful use of ertapenem delivered in a hospital-based OPAT unit for
      TRUSPBx prophylaxis.

PMID- 24680442
TI  - Potential benefit of transrectal saturation prostate biopsy as an initial biopsy
      strategy: decreased likelihood of finding significant cancer on future biopsy.
AB  - OBJECTIVE: To identify the ability of transrectal saturation prostate biopsy
      (SPBx) as the initial diagnostic approach to reduce the likelihood of finding
      previously unrecognized prostate cancer (PCa) during repeat prostate biopsy.
      MATERIALS AND METHODS: We reviewed PCa detection in 561 men who underwent first
      repeat SPBx after initial negative biopsy between March 2002 and April 2012. We
      divided the patients on the basis of the number of cores retrieved on initial
      biopsy (group 1, initial negative SPBx [n = 81] and group 2, initial negative
      extended prostate biopsy [n = 480]). The yield of repeat SPBx was compared
      between the 2 groups. Insignificant PCa and low-risk PCa were defined according
      to Epstein criteria and D'Amico risk criteria, respectively. RESULTS: PCa
      detection on first repeat SPBx was 43.1% lower in group 1 (19.8% vs 34.8%; P =
      .008). Moreover, lower rate of significant PCa (31.3% vs 74.3%; P <.001) and
      intermediate- and/or high-risk PCa (25.0% vs 50.9%; P = .048) in group 1.
      Multivariate analysis confirmed that initial negative SPBx decreased PCa
      detection on first repeat SPBx (odds ratio = 0.41, 95% confidence interval 0.22
      0.78). CONCLUSION: Men whose initial biopsy was per transrectal saturation
      technique were less likely to have cancer identified during repeat biopsy.
      Furthermore, PCa diagnosed after negative initial SPBx was much more likely to be
      clinically insignificant. These findings suggest that SPBx may be less likely to
      miss clinically significant cancer during initial prostate biopsy. If confirmed
      in other studies, this suggests that initial biopsy by saturation technique may
      eliminate the need for most men to undergo repeat biopsy.

PMID- 24680444
TI  - Editorial comment.

PMID- 24680443
TI  - Bladder neck incision for female bladder neck obstruction: long-term outcomes.
AB  - OBJECTIVE: To evaluate the long-term outcomes of bladder neck incision (BNI) for
      primary bladder neck obstruction in women. METHODS: Eighty-four women were
      diagnosed on the basis of videourodynamic study. BNI was performed for each
      patient, with incisions made at 2 different sites on the bladder neck. RESULTS:
      Follow-up data were available for 6-78 months (average, 27.4), postoperatively.
      Successful recovery after BNI without serious complications was achieved in 71 of
      84 (84.5%) patients. During follow-up, the mean International Prostate Symptom
      Score decreased from 22.9 to 7.9 (P <.01). Quality of life decreased from 4.1 to
      2.4 (P <.01). The maximum uroflow rate increased from 9.75 to 18.79 mL/s (P
      <.01). The postvoid residual decreased from 115.11 to 23.29 mL (P <.01). The
      maximal detrusor pressure at the maximum uroflow rate decreased from 69.61 to
      20.48 cm H2O (P <.01). Several complications were identified after surgery,
      including hemorrhage, re-BNI, vesicovaginal fistula (VVF), stress urinary
      incontinence (SUI), and urethral stricture. All these complications were grade
      IIIa in the Clavien Classification of Surgical Complications. Three patients
      (3.6%) developed a VVF after BNI; these VVFs were repaired successfully. Four
      (4.7%) patients experienced SUI and recovered after transvaginal tension-free
      vaginal tape-obturator. Postoperative bleeding was identified in 3 patients
      (3.6%), and 1 received a blood transfusion. Three (3.6%) patients experienced
      urethral stricture after BNI and recovered after receiving intermittent urethral
      dilation. CONCLUSION: Primary bladder neck obstruction is uncommon and easily
      treatable when properly diagnosed by videourodynamic study, and BNI has a high
      success rate. Careful, sufficiently deep incisions at the 2- and 10-o'clock
      positions can ensure its success. Complications such as postoperative VVF or SUI
      can occur and must be actively managed.

PMID- 24680445
TI  - Reply: To PMID 24680443.

PMID- 24680447
TI  - Editorial comment.

PMID- 24680448
TI  - Improvement in clinical TNM staging documentation within a prostate cancer
      quality improvement collaborative.
AB  - OBJECTIVE: To assess the effectiveness of a feedback and educational intervention
      to increase documentation of clinical tumor-node-metastasis (TNM) stage among
      urologists in a statewide quality improvement collaborative. METHODS: The
      Michigan Urological Surgery Improvement Collaborative (MUSIC) is a consortium of
      urology practices that aims to improve the quality and cost-efficiency of
      prostate cancer care. In pilot data collection activities, trained abstractors
      recorded medical record documentation of clinical TNM stage by participating
      urologists. We compared levels of TNM stage documentation in 12 MUSIC practices
      at baseline and after performance feedback and a collaborative-wide educational
      intervention. We examined patient and practice characteristics associated with
      documentation of TNM stage. RESULTS: We accrued 491 and 581 men with newly
      diagnosed prostate cancer during the baseline and postfeedback phases of data
      collection, respectively. At baseline, 58% of patients had clinical TNM staging
      in the medical record, ranging from 19% to 96% across 12 practices (P <.05).
      After the intervention, documentation improved to 79% of patients overall, with 7
      individual practices achieving significant improvements (all P <.05). The
      greatest improvements in documentation occurred among patients treated in smaller
      practices (ie, 1-4 urologists). CONCLUSION: After collaborative review of staging
      criteria and feedback of baseline performance, urologists in MUSIC practices
      dramatically improved documentation of clinical TNM stage. This finding
      underscores the behavioral change possible with the collaborative quality
      improvement model and ensures the necessary risk stratification data for our
      ongoing efforts to improve care.

PMID- 24680446
TI  - Short-term outcomes of vaginal mesh placement among female Medicare
      beneficiaries.
AB  - OBJECTIVE: To compare short-term outcomes between prolapse repairs with and
      without mesh using a national data set. Mesh use in surgical treatment of pelvic
      organ prolapse has gained wide popularity. However, mesh complications have
      increased concomitantly with its use. METHODS: Public Use File data were obtained
      for a 5% random national sample of female Medicare beneficiaries aged 65 years
      and older. Women who underwent prolapse surgery were identified using Current
      Procedural Terminology Coding System, Fourth Edition (CPT-4) codes. Because the
      code for mesh placement was effected in 2005, we separated patients into 3
      cohorts as follows: those who underwent prolapse repairs from 1999 to 2000
      (presumably without mesh), those who underwent repairs from 2007 to 2008
      (presumably without mesh), and those with mesh (based on CPT-4 code 57267) from
      2007 to 2008. One-year outcomes were identified using International
      Classification of Diseases, Ninth Revision diagnosis and procedure codes and CPT
      4 procedure codes. RESULTS: A total of 9180 prolapse repairs without mesh were
      performed from 1999 to 2000, 7729 without mesh from 2007 to 2008, and 1804
      prolapse repairs with mesh from 2007 to 2008. Prolapse reoperation within 1 year
      of surgery was higher in nonmesh vs mesh cohorts (6%-7% vs 4%, P <.02). Mesh
      removal rates were higher in mesh vs nonmesh group (4% vs 0%-1%, P <.001). Mesh
      use was associated with more dyspareunia, mesh-related complications, and urinary
      retention, even when controlling for concomitant sling. CONCLUSION: Mesh to treat
      pelvic organ prolapse and stress urinary incontinence was associated with a small
      decrease in early reoperation for prolapse. This decrease came at the expense of
      increased rates of pelvic pain, retention, mesh-related complications, and mesh
      removal.

PMID- 24680449
TI  - Editorial comment.

PMID- 24680450
TI  - Fluorescence-enhanced robotic radical cystectomy using unconjugated indocyanine
      green for pelvic lymphangiography, tumor marking, and mesenteric angiography: the
      initial clinical experience.
AB  - OBJECTIVE: To describe the initial feasibility of fluorescence-enhanced robotic
      radical cystectomy (FERRC) using real-time cystoscopic injection of unconjugated
      indocyanine green (ICG) for tumor marking and identification of sentinel
      lymphatic drainage with additional intravenous injection for mesenteric
      angiography. METHODS: Ten patients with clinically localized high-grade bladder
      cancer underwent FERRC. Before robot docking, rigid cystoscopy was performed,
      during which a 2.5-mg/mL ICG solution was injected in the bladder submucosa and
      detrusor circumferentially around the tumor. After robot docking, parameters
      describing the time course of tissue fluorescence and pelvic lymphangiography
      were systematically recorded. Lymphatic packets containing fluorescent lymph
      nodes were considered the sentinel drainage. Eight patients underwent
      intracorporeal ileal conduit urinary diversion, during which an additional 2-mL
      ICG solution was given intravenously for mesenteric angiography, allowing maximal
      preservation of bowel vascularity to the conduit and remaining bowel segments.
      RESULTS: Bladder tumor marking and identification of sentinel drainage were
      achieved in 9 of 10 (90%) patients. The area of bladder tumor was identified at a
      median of 15 minutes after injection, whereas sentinel drainage was visualized at
      a median of 30 minutes. Mesenteric angiography was successful in 8 of 8 (100%)
      patients at a median time of <1 minutes after intravenous injection and enabled
      identification of bowel arcades before intracorporeal bowel stapling. CONCLUSION:
      FERRC using combined cystoscopic and intravenous injection of ICG is safe and
      feasible. FERRC allows for reliable bladder tumor marking, identification of
      sentinel lymphatic drainage, and identification of mesenteric vasculature in most
      patients.

PMID- 24680451
TI  - Editorial comment.

PMID- 24680452
TI  - Reply: To PMID 24680451.

PMID- 24680453
TI  - Sildenafil improves erectile hardness in Chinese men with erectile dysfunction: a
      real-life study analyzed on age stratification.
AB  - OBJECTIVE: To evaluate the clinical efficacy of sildenafil for the improvement of
      penile erection hardness in erectile dysfunction (ED) patients and to determine
      the relationship between this improvement in erection hardness and social and
      psychological functioning. MATERIALS AND METHODS: From 2007 to 2008, a total of
      4507 men diagnosed with ED were enrolled from 46 centers in China; 4039 of these
      patients were treated with sildenafil and asked to complete the Erectile Function
      domain of the International Index of Erectile Function, Erection Hardness Score,
      and Quality of Erection Questionnaire. The patients were divided into 5 groups on
      the basis of their age (group A: 20-30 years; group B: 31-40 years; group C: 41
      50 years; group D: 51-60 years; and group E: >60 years). RESULTS: A total of 3837
      (95.0%) patients completed the entire study. After sildenafil treatment, the vast
      majority (96.3%) of the men were able to achieve grade 3-4 erection hardness.
      Patients with a better baseline erection hardness were more able to achieve grade
      4 hardness after treatment (P <.001). Comparisons of the Erection Hardness Score
      improvement before and after treatment between the age-categorized groups also
      showed that the erection hardness improvement was much greater in men older than
      50 years. CONCLUSION: Sildenafil can help the vast majority of Chinese ED
      patients achieve grade 3-4 erection hardness. Grade 4 hardness can improve the
      patients' sexual life to a greater extent than grade 3 hardness. A marked
      improvement in erection hardness can be achieved in patients older than 50 years.

PMID- 24680454
TI  - Can treatment of nocturia increase testosterone level in men with late onset
      hypogonadism?
AB  - OBJECTIVE: To assess the effect of desmopressin on serum testosterone level in
      men with nocturia and late onset hypogonadism. METHODS: We prospectively enrolled
      men with nocturia and symptoms of late onset hypogonadism. Desmopressin (0.1 mg)
      was administered once daily to patients for 12 weeks, and we then compared serum
      testosterone levels, electrolytes, frequency volume chart indices, and changes in
      the International Prostate Symptom Score (IPSS), International Index of Erectile
      Function, and Aging Male's Symptom scales before and after treatment. Patients
      with a history of cardiovascular disease or hyponatremia, those using hypnotics,
      and those who had primary hypogonadism or hypogonadotrophic hypogonadism were
      excluded from the study. RESULTS: Sixty-two men (mean age, 68.4 years) completed
      pre- and post-treatment questionnaires and underwent laboratory testing. At the
      end of the study, the testosterone levels in men with low testosterone levels
      (<3.5 ng/mL) increased after the 12-week desmopressin treatment (2.85 +/- 0.58 to
      3.97 +/- 1.44 ng/mL; P = .001). Mean scores had decreased from 17.7 to 13.9
      (IPSS), 3.8 to 3.2 (IPSS-Quality of Life), and 33.7 to 31.1 (Aging Male's
      Symptom). On the frequency volume chart, nocturnal urine volume, nocturnal
      polyuria index, actual number of nocturia events, nocturia index, and nocturnal
      bladder capacity index were significantly decreased. CONCLUSION: Desmopressin
      improved nocturia and other urinary symptoms. Moreover, serum testosterone levels
      increased significantly in men with low testosterone levels after 12-week
      desmopressin treatment.

PMID- 24680456
TI  - Editorial comment.

PMID- 24680455
TI  - Assessing the burden of complications after surgery for clinically localized
      kidney cancer by age and comorbidity status.
AB  - OBJECTIVE: To examine the association between high-risk patient status (age >75
      years or Charlson comorbidity index count >2) and postoperative complications in
      patients undergoing surgical management for clinically localized renal tumors.
      MATERIALS AND METHODS: Patients undergoing radical nephrectomy (RN) or partial
      nephrectomy (PN) (2005-2012) for localized renal cell carcinoma were analyzed.
      Multivariate logistic regressions were used to test the association between high
      risk status and postoperative complications adjusting for patient, tumor, and
      operative characteristics. RESULTS: Of 1092 patients undergoing PN (71.9%) or RN
      (28.1%) for clinically localized renal tumors, 255 (23.4%) were classified as
      high risk, and 175 patients (16%) developed at least 1 complication (mean 1.6 +/-
      1.0). Of note, 22.4% and 14.1% of high- and low-risk patients developed a
      complication, respectively (P = .002). Comparing high- and low-risk patients,
      significant differences in Clavien I-II (20.4% vs 11.1%; P <.001) and medical
      (16.1% vs 8.1%, P <.001) complications were observed, whereas no differences were
      seen in Clavien III-V or surgical complications. No differences in complications
      were observed comparing patients treated with RN and PN, albeit high-risk
      patients were more likely to undergo RN (35.3% vs 25.9%, P = .04). After
      adjustment, the odds of incurring any complication were 1.9 times higher in high-
      compared with low-risk patients (odds ratio 1.9 [confidence interval 1.3-2.8]).
      CONCLUSION: Regardless of surgical type, patients deemed high risk by age and
      comorbidity criteria were more likely to incur a postoperative complication after
      renal mass resection. Improved understanding of surgical risks in the elderly and
      infirmed will help better inform patients deciding between active surveillance
      and resection of renal tumors.

PMID- 24680457
TI  - Biopsy criteria for determining appropriateness for active surveillance in the
      modern era.
AB  - OBJECTIVE: To evaluate algorithms to predict insignificant prostate cancer at
      radical prostatectomy (RP). METHODS: Five hundred and fifty men (410 Caucasian,
      100 African American [AA], and 40 others) with prostate-specific antigen (PSA)
      level <10 ng/dL, T1c, 12-core biopsy, and biopsy Gleason score 3 + 3 = 6 were
      categorized into training and validation sets. Six biopsy algorithms were tested
      for predicting insignificant (0.5 cm(3), organ confined, and Gleason score <=6)
      cancer at RP. Cancers incorrectly predicted to be insignificant were ranked into
      4 groups of increasing aggressiveness. RESULTS: Original (Gleason score <=6, PSA
      density <=0.15, <=2 positive cores, and maximum core involvement <=50%) and
      modified Epstein criteria (Gleason score <=6, PSA density <=0.15, <=2 positive
      cores, and unilateral cancer) had the highest negative predictive values-correct
      classification of insignificant cancer. Among cancers predicted to be
      insignificant in Caucasians, 29.9% cases using the original and 27% cases using
      the modified Epstein criteria had significant cancer at RP. However, more adverse
      findings at RP were misclassified as insignificant in only 3.5% and 2.2% of cases
      using the original and modified Epstein criteria, respectively. Of cancers
      predicted insignificant in AA men, 54.1% cases using the original and 51.6% cases
      using the modified Epstein criteria were misclassified as insignificant. Dominant
      anterior tumors were seen in 117 Caucasian (28.5%) and 44 AA men (44%).
      CONCLUSION: The Epstein criteria maintain their accuracy in the modern era with
      extended biopsy sampling. The negative predictive values are lower in AA men, in
      part due to higher frequency of anterior tumors, where multiparametric magnetic
      resonance imaging should be recommended in AAs considering surveillance.

PMID- 24680458
TI  - Striated muscle in the prostatic apex: does the amount in radical prostatectomy
      specimens predict postprostatectomy urinary incontinence?
AB  - OBJECTIVE: To investigate whether the amount of striated muscle (SM) removed with
      the apical aspect of the prostate at prostatectomy can be predictive of
      postprostatectomy urinary incontinence (UI). METHODS: The records of 61
      consecutive patients seen in follow-up after prostatectomy were reviewed.
      Complete clinical data were collected. Two uropathologists reviewed the
      hematoxylin and eosin sections of the apical margin to semiquantitatively assess
      the amount of SM according to the following scheme: 0 = no SM, 1 = 1%-10% SM (of
      total tissue), 2 = 11%-30% SM, and 3 = >30% SM. Continence status was determined
      based on the last clinical visit, with UI considered as any reported leakage.
      RESULTS: Patients had a median age of 62 years at surgery (interquartile range,
      58-66 years) and had a median follow-up after surgery of 100 weeks (interquartile
      range, 50-176 weeks). Both prostate weight and SM score (P = .045 for both) were
      statistically significant predictors of incontinence on multivariate analysis.
      The odds of a patient with an average SM score of >=2 being incontinent was 11.7
      times that of a patient with an average score of <2. Using an SM score of >=2 had
      a specificity of 98% and a sensitivity of 19% for detecting incontinence in
      patients after radical prostatectomy. CONCLUSION: The amount of SM seen in the
      pathology specimen after radical prostatectomy has a significant effect on
      postoperative UI.

PMID- 24680459
TI  - Primary realignment vs suprapubic cystostomy for the management of pelvic
      fracture-associated urethral injuries: a systematic review and meta-analysis.
AB  - OBJECTIVE: To compare primary urethral realignment (PR) with suprapubic
      cystostomy (SPC) for the management of pelvic fracture-associated posterior
      urethral injuries with regards to rates of stricture, erectile dysfunction, and
      urinary incontinence. METHODS: Two electronic databases (MEDLINE and EMBASE) were
      searched with the assistance of a librarian. Title, abstract, and full text
      screening was carried out by 2 independent reviewers, with discrepancies resolved
      by consensus. Narrative reviews, surveys, and historical articles were excluded.
      Only studies reporting a direct comparison of PR vs SPC for the management of
      posterior urethral injuries associated with blunt trauma in adults were included.
      Quality assessment of the included articles was performed in duplicate. Stricture
      incidence was evaluated for all included studies, as were erectile dysfunction
      and incontinence rates when reported. All outcomes were treated as dichotomous
      data with calculation of odds ratio and were pooled using a random effects model
      with Review Manager 5.1. RESULTS: Our comprehensive search yielded 161 unique
      articles. Nine articles were included in the final meta-analysis. Stricture rate
      was significantly lower in the PR group (odds ratio [OR] = 0.12, 95% confidence
      interval [CI] 0.04-0.41, P <.001). There was no significant difference between
      the 2 interventions with regards to erectile dysfunction (OR = 1.19, 95% CI 0.73
      1.92, P = .49) or incontinence (OR = 0.75, 95% CI 0.38-1.48, P = .41).
      CONCLUSION: PR appears to reduce the incidence of stricture formation after
      pelvic fracture-associated posterior urethral injuries as compared with SPC.

PMID- 24680460
TI  - Controversies in the treatment of male hypogonadism.

PMID- 24680461
TI  - Re: Wong et al.: Is percutaneous nephrolithotomy in solitary kidneys safe?
      (Urology 2013;82:1013-1016).

PMID- 24680462
TI  - Re: Kim et al.: The efficacy of extracorporeal magnetic stimulation for treatment
      of chronic prostatitis/chronic pelvic pain syndrome patients who do not respond
      to pharmacotherapy (Urology 2013;82:894-898).

PMID- 24680463
TI  - Reply by the authors.

PMID- 24680464
TI  - Reply by the authors.

PMID- 24680465
TI  - Re: Saravakos et al.: Cystinuria: current diagnosis and management (Urology
      2013;83:693-699).

PMID- 24680466
TI  - Progressive changes in atrial tachyarrhythmias with reversal of hyperkalemia.

PMID- 24680467
TI  - Biomechanical evaluation of fracture fixation constructs using a variable-angle
      locked periprosthetic femur plate system.
AB  - BACKGROUND: In the United States there are more than 230,000 total hip
      replacements annually, and periprosthetic femoral fractures occur in 0.1-4.5% of
      those patients. The majority of these fractures occur at the tip of the stem
      (Vancouver type B1). The purpose of this study was to compare the biomechanically
      stability and strength of three fixation constructs and identify the most
      desirable construct. METHODS: Fifteen medium adult synthetic femurs were
      implanted with a hip prosthesis and were osteotomized in an oblique plane at the
      level of the implant tip to simulate a Vancouver type B1 periprosthetic fracture.
      Fractures were fixed with a non-contact bridging periprosthetic proximal femur
      plate (Zimmer Inc., Warsaw, IN). Three proximal fixation methods were used: Group
      1, bicortical screws; Group 2, unicortical screws and one cerclage cable; and
      Group 3, three cerclage cables. Distally, all groups had bicortical screws.
      Biomechanical testing was performed using an axial-torsional testing machine in
      three different loading modalities (axial compression, lateral bending, and
      torsional/sagittal bending), next in axial cyclic loading to 10,000 cycles, again
      in the three loading modalities, and finally to failure in torsional/sagittal
      bending. RESULTS: Group 1 had significantly greater load to failure and was
      significantly stiffer in torsional/sagittal bending than Groups 2 and 3. After
      cyclic loading, Group 2 had significantly greater axial stiffness than Groups 1
      and 3. There was no difference between the three groups in lateral bending
      stiffness. The average energy absorbed during cyclic loading was significantly
      lower in Group 2 than in Groups 1 and 3. CONCLUSIONS: Bicortical screw placement
      achieved the highest load to failure and the highest torsional/sagittal bending
      stiffness. Additional unicortical screws improved axial stiffness when using
      cable fixation. Lateral bending was not influenced by differences in proximal
      fixation. CLINICAL RELEVANCE: To treat periprosthetic fractures, bicortical screw
      placement should be attempted to maximize load to failure and torsional/sagittal
      bending stiffness.

PMID- 24680468
TI  - The outcome of patients sustaining a proximal femur fracture who suffer from
      alcohol dependency.
AB  - There are many negative health consequences associated with alcohol dependency.
      Fractures of the proximal femur carry significant morbidity and mortality. This
      study examines the outcomes in patients with alcohol dependency, who sustain a
      fracture of the proximal femur. Twenty-eight consecutive alcohol dependent
      patients who suffered a fracture of the proximal femur were identified over a
      three year period. Data were collected on demographics, co-morbidity, surgical
      factors, mobility and mortality. The median age of patients was 61 years. The
      median weekly alcohol intake was 158 units. Thirteen patients sustained an extra
      capsular fracture and 15 an intra-capsular proximal femoral fracture. Twenty-two
      fractures were treated with internal fixation and six with arthroplasty. The
      overall mortality rate was 29% at a median of 15 months post fracture. The
      failure rate of intra-capsular fractures fixed with cannulated screws was 56% at
      a median time of 43 days. All patients had a reduction in mobility compared to
      their pre-operative function. The reduction in mobility was greatest in patients
      with intra-capsular fractures treated with cannulated screw fixation. Alcohol
      dependent patients sustaining a fracture of the proximal femur are significantly
      younger than non-alcohol dependent patients sustaining the same injury. Despite
      the younger age at presentation the one year mortality rate of this group was
      high (29%). The high rate of complications with fracture fixation and high one
      year mortality suggest that hemiarthroplasty may be the best treatment option for
      intra-capsular fractures in this patient group. 

PMID- 24680469
TI  - Clinical features of periorbital ecchymosis in a series of trauma patients.

PMID- 24680470
TI  - A prospective look at the burden of sharps injuries and splashes among trauma
      health care workers in developing countries: true picture or tip of iceberg.
AB  - OBJECTIVES: Health care workers (HCWs) face constant risk of exposure to cuts and
      splashes as occupational hazard. Hence, a prospective observational study was
      conducted to observe the exposure of HCWs to various sharp injuries and splashes
      during health care and to work up a baseline injury rate among HCWs for future
      comparison in trauma care set ups. METHODS: A 2 year and 5 month study was
      conducted among the voluntarily reported exposed HCWs of the APEX trauma centre.
      Such reported cases were actively followed for 6 months after testing for viral
      markers and counselled. The outcomes of such exposed HCWs and rate of
      seroconversion was noted. To form a future reference point, the injury rate in
      trauma care HCWs based on certain defined parameters along with the rate of under
      reporting were also analysed in this study. RESULTS: In our study, doctors were
      found to have the highest exposure (129, 36.2%), followed by nurses (52, 14.6%)
      and hospital waste disposal staff (27, 7.6%). Of the source patients, a high
      number of them were HBV positive (11, 3.1%), followed by HIV positive patients
      (8, 2.2%). No seroconversion was seen in any of the exposed HCWs. Injuries by
      sharps (303, 85.1%) outnumber those due to splashes (53, 14.9%) which were much
      higher in those working in pressing situations. Underreporting was common, being
      maximally prevalent in hospital waste disposal staff (182, 51.1%). CONCLUSIONS:
      High rates of exposure to sharp injuries and splashes among HCWs call for proper
      safety protocols. Proper methods to prevent it, encouraging voluntary reporting
      and an active surveillance team are the need of the hour.

PMID- 24680471
TI  - A procedural check list for pleural decompression and intercostal catheter
      insertion for adult major trauma.
AB  - BACKGROUND: Intercostal catheter (ICC) insertion is the standard pleural
      decompression and drainage technique for blunt and penetrating traumatic injury.
      Potentially high complication rates are associated with the procedure, with the
      literature quoting over 20% in some cases (1-4). Empyema in particular is a
      serious complication. Risk adverse industries such as the airline industry and
      military services regularly employ checklists to standardise performance and
      decrease human errors. The use of checklists in medical practice is exemplified
      by introduction of the WHO Surgical Safety checklist. METHODS: The Alfred
      Hospital in Melbourne, Australia is an Adult Level 1 Trauma Centre. In August
      2009 The Alfred Trauma Service introduced an evidence-based checklist system for
      the insertion of ICCs, combined with standardised formal training for resident
      medical staff, in an attempt to minimise the incidence of ICC related empyema.
      RESULTS: Between January 2003 and July 2009 the incidence of empyema was 1.44%
      (29 in 2009 insertions). This decreased to 0.57% between August 2009 and December
      2011 (6 in 1060 insertions) when the measures described above were introduced
      [p=0.038 Fisher's exact test, 2-tailed]. CONCLUSION: Quality control checklists -
      such as the ICC checklist described - are a sensible and functional means to
      standardise practice, to decrease procedural error and to reduce complication
      rates during trauma resuscitation.

PMID- 24680472
TI  - Assessing the burden of diabetes mellitus in emergency departments in the United
      States: the National Hospital Ambulatory Medical Care Survey (NHAMCS).
AB  - OBJECTIVE: To evaluate the performance of three alternative methods to identify
      diabetes in patients visiting Emergency Departments (EDs), and to describe the
      characteristics of patients with diabetes who are not identified when the
      alternative methods are used. RESEARCH DESIGN AND METHODS: We used data from the
      National Hospital Ambulatory Medical Care Survey (NHAMCS) 2009 and 2010. We
      assessed the sensitivity and specificity of using providers' diagnoses and
      diabetes medications (both excluding and including biguanides) to identify
      diabetes compared to using the checkbox for diabetes as the gold standard. We
      examined the characteristics of patients whose diabetes was missed using
      multivariate Poisson regression models. RESULTS: The checkbox identified 5,567 ED
      visits by adult patients with diabetes. Compared to the checkbox, the sensitivity
      was 12.5% for providers' diagnoses alone, 20.5% for providers' diagnoses and
      diabetes medications excluding biguanides, and 21.5% for providers' diagnoses and
      diabetes medications including biguanides. The specificity of all three of the
      alternative methods was >99%. Older patients were more likely to have diabetes
      not identified. Patients with self-payment, those who had glucose measured or
      received IV fluids in the ED, and those with more diagnosis codes and
      medications, were more likely to have diabetes identified. CONCLUSIONS: NHAMCS's
      providers' diagnosis codes and medication lists do not identify the majority of
      patients with diabetes visiting EDs. The newly introduced checkbox is helpful in
      measuring ED resource utilization by patients with diabetes.

PMID- 24680473
TI  - Spread of a carbapenem- and colistin-resistant Acinetobacter baumannii ST2 clonal
      strain causing outbreaks in two Sicilian hospitals.
AB  - BACKGROUND: Infections caused by multidrug-resistant (MDR) Acinetobacter
      baumannii have become an important healthcare-associated problem, particularly in
      intensive care units (ICUs). AIM: To investigate the emergence of carbapenem- and
      colistin-resistant A. baumannii infections in two Sicilian hospitals. METHODS:
      From October 2008 to May 2011, a period which included two Italian Nosocomial
      Infections Surveillance in ICUs network (SPIN-UTI) project surveys, all
      carbapenem-resistant A. baumannii isolates from the ICUs of two hospitals in
      Catania, Italy, were prospectively collected. Minimum inhibitory concentrations
      (MICs) were measured by agar dilution, and phenotypic testing for metallo-beta
      lactamase (MBL) production was performed. Carbapenem resistance genes and their
      genetic elements were identified by polymerase chain reaction and sequencing.
      Genotypic relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and
      multi-locus sequence typing. Patient-based surveillance was conducted using the
      SPIN-UTI protocol and previous antibiotic consumption was recorded. FINDINGS:
      Twenty-six carbapenem-resistant A. baumannii were identified. Imipenem and
      meropenem MICs ranged from 4 to >32 mg/L, and 15 isolates exhibited high-level
      colistin resistance (MICs >32 mg/L). PFGE demonstrated that all isolates belonged
      to a unique clonal type and were assigned to ST2 of the international clone II.
      They harboured an intrinsic blaOxA-51-like carbapenemase gene, blaOxA-82, which
      was flanked upstream by ISAba1. CONCLUSIONS: The dissemination of clonally
      related isolates of carbapenem-resistant A. baumannii in two hospitals is
      described. Simultaneous resistance to colistin in more than half of the isolates
      is a problem for effective antibiotic treatment. Prior carbapenem and colistin
      consumption may have acted as triggering factors.

PMID- 24680474
TI  - New hydronephrosis and/or vesicoureteral reflux after bladder outlet surgery
      without augmentation in 75 children with neurogenic bladder.
AB  - OBJECTIVE: We report new upper tract changes in children after bladder neck (BN)
      surgery without augmentation for neurogenic incontinence. MATERIALS AND METHODS:
      Consecutive children with neurogenic sphincteric incompetency had BN surgery
      without augmentation. Postoperative renal sonography and fluoroscopic urodynamics
      were done at 6 months, 12 months, and then annually. RESULTS: There were 75
      patients with mean follow-up of 48 months. Of these, 17 (23%) developed new
      hydronephrosis (HN) or vesicoureteral reflux (VUR). All HN resolved with medical
      management, as did 25% of VUR cases. Persistent VUR was treated by
      dextranomer/hyaluronic acid injection, or re-implantation in two patients
      undergoing re-operative BN surgery. There was no association between these upper
      tract changes and end filling pressures (<40 cm vs. >40 cm) or continence status
      (dry vs. wet). CONCLUSIONS: Upper tract changes developed in 25% of patients with
      neurogenic bladders after BN surgery without augmentation during a follow-up of
      48 months. All new HN and most new VUR resolved with medical management or
      minimally invasive intervention. No patient developed upper tract changes
      requiring augmentation.

PMID- 24680475
TI  - The role of IL-4 gene 70 bp VNTR and ACE gene I/D variants in Familial
      Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever
      and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. It
      is an autosomal recessive disease caused by mutations in the MEFV (MEditerranean
      FeVer) gene. Patients with similar genotypes exhibit phenotypic diversity. As a
      result, the variations in different genes could be responsible for the clinical
      findings of this disease. In previous studies genes encoding Angiotensin
      Converting Enzyme (ACE) and IL-4 (Interleukin-4) were found to be associated with
      rheumatologic and autoimmune diseases. In the present study we hypothesized
      whether ACE I/D or IL-4 70 bp variable tandem repeats (VNTR) genes are associated
      with FMF and its clinical findings in Turkish patients. Genomic DNA obtained from
      670 persons (339 patients with FMF and 331 healthy controls) was used in the
      study. Genotypes for an ACE gene I/D polymorphism and IL-4 gene 70 bp VNTR were
      determined by polymerase chain reaction with specific primers. To our knowledge,
      this is the first study examining ACE gene I/D polymorphism and IL-4 gene 70 bp
      VNTR polymorphism in FMF patients. As a result, there was a statistically
      significant difference between the groups with respect to genotype distribution
      (p<0.001). According to our results, ACE gene DD genotype was associated with an
      increased risk in FMF [p<0.001; OR (95%): 7.715 (4.503-13.22)]. When we examined
      ACE genotype frequencies according to the clinical characteristics, we found a
      statistically significant association between DD+ID genotype and fever (p=0.04).
      In addition IL-4 gene P1P1 genotype was associated with FMF (p<0.001). We propose
      that D allele or DD genotype of ACE gene and P1 allele or P1P1 genotype of IL-4
      gene may be important molecular markers for susceptibility of FMF.

PMID- 24680476
TI  - Human monocytes produce interferon-gamma upon stimulation with LPS.
AB  - Representing a crucial T-helper 1 cytokine, IFN-gamma acts as an important bridge
      between innate and adaptive immunity and is involved in many acute and chronic
      pathologic states, such as autoimmune diseases and solid organ transplant
      rejection. At present, debate still prevails about the ability of human monocytes
      to produce IFN-gamma. We aimed to investigate whether human monocytes possess the
      capacity to produce IFN-gamma at mRNA and protein level. Using real time PCR,
      flow cytometric analysis and ELISA, we investigated the capacity of freshly
      isolated CD14+ monocytes of healthy individuals and kidney transplant recipients
      to produce IFN-gamma after stimulation with IFN-gamma and LPS or LPS alone. We
      observed increased IFN-gamma mRNA levels in CD14+ monocytes after stimulation as
      compared to the unstimulated controls in both populations. In addition,
      stimulation with IFN-gamma and LPS or LPS alone led to a significant increase in
      the percentage of CD14+ monocytes producing TNF-alpha and IFN-gamma at protein
      level (p<0.05). A trend towards increased secreted IFN-gamma production in
      supernatants was also observed after LPS stimulation using ELISA. We conclude
      that human monocytes from healthy individuals and kidney transplant recipients
      possess the capacity to produce IFN-gamma. 

PMID- 24680477
TI  - Antimalarial drugs inhibit IFNalpha-enhanced TNFalpha and STAT4 expression in
      monocytes: implication for systemic lupus erythematosus.
AB  - OBJECTIVES: To analyse the influence of IFNalpha on TNFalpha production by human
      peripheral blood mononuclear cells (PBMCs), as well as the possible interference
      of this cytokine on the effect of antimalarial drugs, TNFalpha regulators widely
      used in the treatment of systemic lupus erythematosus (SLE). METHODS: PBMCs,
      monocytes or T cells were treated with IFNalpha alone or simultaneously to
      cellular stimuli as well as in the presence or absence of chloroquine.
      Supernatants from such cultures were collected to quantify TNFalpha by ELISA.
      TNFalpha and STAT4 expression in cultured cells were analysed by intracellular
      flow cytometry. In addition, STAT4 gene expression and serum levels of TNFalpha
      and IFNalpha were quantified in 53 SLE patients and 45 controls. RESULTS:
      IFNalpha alone did not modify significantly TNFalpha production, but an increase
      was observed in stimulated PBMC. Further analyses showed that monocytes were the
      cellular population responsible for this effect. In addition, IFNalpha treatment
      increased STAT4 in stimulated monocytes, suggesting that TNFalpha upregulation
      could be mediated by STAT4. On the other hand, the analysis of the antimalarial
      effect showed that chloroquine was able to inhibit in vitro the expression of
      TNFalpha and STAT4 enhanced by IFNalpha. In antimalarial-treated SLE patients,
      however, only those with high IFNalpha serum levels presented lower expression of
      STAT4. CONCLUSIONS: IFNalpha treatment enhances the induction of TNFalpha and
      STAT4 in stimulated monocytes, an effect inhibited in vitro by chloroquine
      treatment. However, the consequence of antimalarial treatment on SLE patients
      could be different depending on their IFNalpha serum levels.

PMID- 24680478
TI  - Safety and feasibility of long term administration of recombinant human
      granulocyte-colony stimulating factor in patients with amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neuronal disease
      resulting in a loss of the upper and lower motor neurons and subsequent death
      within three to four years after diagnosis. Mouse models and preliminary human
      exposure data suggest that the treatment with granulocyte-colony stimulating
      factor (G-CSF) has neuro-protective effects and may delay ALS progression. As
      data on long-term administration of G-CSF in patients with normal bone marrow
      (BM) function are scarce, we initiated a compassionate use program including 6
      ALS patients with monthly G-CSF treatment cycles. Here we demonstrate that G-CSF
      injection was safe and feasible throughout our observation period up to three
      years. Significant decrease of mobilization efficiency occurred in one patient
      and a loss of immature erythroid progenitors was observed in all six patients.
      These data imply that follow-up studies analyzing BM function during long-term G
      CSF stimulation are required. 

PMID- 24680479
TI  - Cytokines and chemokines are differentially expressed in patients with
      periodontitis: possible role for TGF-beta1 as a marker for disease progression.
AB  - Periodontitis is a chronic inflammatory disease characterized by destruction of
      periodontal tissue ultimately leading to bone destruction and has been associated
      with other inflammatory diseases, such as atherosclerosis. Attachment loss of
      periodontal tissue is primarily caused by host cell-derived immune responses
      against subgingival biofilm. The aim of the present study was to determine the
      cytokine profile in serum, saliva and gingival crevicular fluid (GCF) patients
      with periodontitis and healthy controls. We show that periodontitis patients
      exhibit higher numbers of periodontal pathogens and their immune responses are
      significantly altered. The levels of IL-6 in saliva and GCF were significantly
      suppressed, and while CXCL8 was not altered in serum, its expression levels were
      significantly suppressed in saliva and elevated in GCF. The T-cell-derived
      cytokine IL-2 did not differ between patients and controls in serum and saliva,
      but there was a significant suppression in GCF of patients. Interestingly, TGF
      beta1 levels were significantly elevated in serum, saliva and GCF in patients
      compared to controls. Furthermore, by using cultured gingival fibroblasts
      stimulated with wild type and proteinase mutant strains of Porphyromonas
      gingivalis, we show that the suppression of CXCL8 and IL-6, and the induction of
      TGF-beta1 is primarily mediated by the proteolytic activity of lysine-specific
      proteinases. These results indicate that P. gingivalis is a major contributor to
      the altered immune responses and the pathology of periodontitis. Furthermore, the
      ease of sampling and analyzing cytokine expression profiles, including TGF-beta1,
      in saliva and GCF may serve to predict the progression of periodontitis and
      associated systemic inflammatory diseases. 

PMID- 24680481
TI  - IL-15 controls T cell functions through its influence on CD30 and OX40 antigens
      in Celiac Disease.
AB  - AIM: To evaluate the ability of interleukin (IL)-15 to control T cell functions
      through its influence on CD30 and OX40 expressing cells in Celiac Disease (CD).
      In peripheral blood (PB), by examining the expression of OX40 in conventional
      effectors cells and T cells with a phenotypic specialization of regulatory cells
      [CD4+CD25high forkhead box protein 3 (Foxp3)+], and the co stimulation of IFN
      gamma and IL-4 production within CD30 and OX40 positive subsets of T cells. At
      the duodenal mucosa, by assessing the expression of CD30 and OX40 in
      intraepithelial (IE) and lamina propria (LP) lymphocytes (IEL, LPL). PATIENTS AND
      METHODS: PB and duodenal mucosal biopsies were obtained from 38 patients with
      classic CD (Cel) and 38 healthy controls (HC). Analysis of cell surface and/or
      intracellular antigens was performed in anti-CD3-treated PB mononuclear cells
      (PBMC) before and after treatment with recombinant IL-15 (rIL-15), and in IE and
      LP cellular suspensions prepared from duodenal biopsies pre-treated with/without
      rIL-15. RESULTS: A subpopulation of CD3+OX40+ T blasts was induced in Cel and HC
      by a 3days treatment of PBMC with anti-CD3 and decreased its size thereafter,
      regardless of the presence of rIL-15. However, the addition of rIL-15 to T blasts
      distinctively induced the survival of T cells with a regulatory phenotype that
      expresses OX40 antigen in Cel (p<0.05). Celiac patients showed higher frequencies
      of IFN-gamma-producing CD3+CD30+ blasts before and after treatment with rIL-15
      (p<0.05, vs. HC). IL-15 increased the frequencies of CD3+CD30+ LPL (HC: p<0.05,
      Cel: p<0.05) but not of CD3+OX40+ LPL, and CD30 or OX40 positive IEL.
      CONCLUSIONS: The distinctive control of OX40+ cells with a T regulatory phenotype
      mediated by the influence of IL-15 comes out as new function of this cytokine in
      the context of CD. The higher production of IFN-gamma by a subpopulation of
      peripheral CD3+CD30+ cells contributes to the type I biased immune response.

PMID- 24680480
TI  - Human neutrophils produce IL-12, IL-10, PGE2 and LTB4 in response to
      Paracoccidioides brasiliensis. Involvement of TLR2, mannose receptor and dectin
      1.
AB  - The functions of phagocytic cells against pathogens are initiated by the
      interaction between membrane receptors and molecular structures which compose the
      cell wall of these microorganisms. Thus our study aimed to identify the
      neutrophil receptors involved in the recognition of different strains of
      Paracoccidioides brasiliensis and the consequent modulation of immune response
      through the production of cytokines and inflammatory mediators. Neutrophils did
      not produce TNF-alfa in response to both strains. However, these cells produce IL
      12, mainly in response to Pb 265, with participation of TLR2 and dectin-1. These
      cells also produce L-10, whose levels were higher for Pb 18 with involvement of
      TLR2 and MR and only TLR2 for Pb 265. The production of PGE2 and LTB4 was
      detected similarly for the two strains. For PGE2, MR and dectin-1 were involved,
      while in relation to LTB4, none of them. In summary, we demonstrated that
      neutrophils have a dynamic role during host immune response to P. brasiliensis,
      since in addition to their role as effector cells of innate immunity; they have
      the capacity to modulate innate and adaptative immune response against this
      fungus by producing cytokines and lipidic mediators. This modulation may be
      toward a pro- or anti-inflammatory pattern in a dependence of P. brasiliensis
      strains and PRR involved in fungus recognition by these cells. 

PMID- 24680483
TI  - Preparation and evaluation of a novel star-shaped polyacid-constructed dental
      glass-ionomer system.
AB  - OBJECTIVE: The objective of this study was to synthesize and characterize novel
      star-shaped poly(acrylic acid-co-itaconic acid)s via chain-transfer radical
      polymerization technique, use these polyacids to formulate the resin-modified
      glass-ionomer cements, and evaluate the mechanical strengths of the formed
      cements MATERIALS AND METHODS: The star-shaped poly(acrylic acid-co-itaconic
      acid)s were synthesized via a chain-transfer radical polymerization reaction
      using a newly synthesized star-shaped chain-transfer agent. The effects of MW, GM
      tethering ratio, P/L ratio and aging on the compressive properties of the formed
      experimental cements were studied. Compressive, diametral tensile as well as
      flexural strengths were evaluated and compared to those of Fuji II and Fuji II LC
      cements. RESULTS: The star-shaped polyacids showed significantly lower
      viscosities in water as compared to their linear counterparts. The cements
      formulated with these novel polyacids showed significantly improved mechanical
      strengths i.e., 49% in yield strength, 41% in modulus, 25% in CS, 20% in DTS and
      36% in FS, higher than commercial Fuji II LC. After aging in water for 30 days,
      the compressive strengths of the experimental cements were significantly changed
      with an increase of 29% in YS, 19% in modulus as well as 23% in CS and a decrease
      of 5% in toughness, indicating that aging in water enhances the salt-bridge
      formation and increases brittleness. CONCLUSIONS: A novel light-cured glass
      ionomer cement system composed of the star-shaped poly(carboxylic acid)s has been
      developed via a cost-effective and time-efficient chain-transfer radical
      polymerization.

PMID- 24680482
TI  - Expression of core-binding factor alpha1 and osteocalcin in fluoride-treated
      fibroblasts and osteoblasts.
AB  - To study the effects and importance of fluoride on FBs in the development of
      extraperiosteal calcification and the ossification of skeletal fluorosis, the
      presence of the osteogenic phenotype, which is indicated by the expression of
      core-binding factor alpha1 (Cbfa1) and osteocalcin (OCN), in an FB cell line
      (L929) and in osteoblasts (OBs) exposed to fluoride was determined. Fibroblasts
      and osteoblasts were exposed to different concentrations of fluoride (0, 0.0001,
      0.001, 0.1, 1.0, 10.0 and 20.0 mg/L F(-)). By using RT-PCR and ELISA, the mRNA
      levels of Cbfa1 and OCN were measured at 48 h, and the protein levels of Cbfa1
      and OCN were measured at 2, 4, 24, 48 and 72 h. The data demonstrated the
      following: (1) The Cbfa1 protein level in fluoride-treated fibroblasts clearly
      increased at 48 h in the groups treated with 0.0001, 0.001, 0.1, 1.0 and 20.0
      mg/L F(-). The Cbfa1 protein level of the group treated with 10 mg/L F(-) at 72 h
      was higher than that of the control group. The level of Cbfa1 mRNA in the
      fibroblasts was much higher at 48 h in the group treated with 10.0 mg/L F(-) than
      in the control group. (2) The OCN protein level in fluoride-treated fibroblasts
      was significantly higher than that of the control group in the 0.0001, 0.1, 1.0,
      10.0 and 20.0 mg/L F(-) groups at 2 h, and in the 0.001 and 0.1 F(-) groups at 4
      h. A slightly higher level of OCN mRNA in fluoride-treated fibroblasts was also
      found in the 1.0 and 20.0 mg/L F(-) groups compared to the control group. (3) The
      expressions of Cbfa1 and OCN in osteoblasts treated with the same experimental
      conditions as the fibroblasts were up-regulated by fluoride following the same
      trend as in the fibroblasts. Our results showed an increase in the expression of
      Cbfa1 and OCN in fibroblasts and osteoblasts exposed to fluoride and suggested
      that the osteogenic function of fibroblasts induced by fluoride could play an
      important role in the development of extraperiosteal ossification during skeletal
      fluorosis.

PMID- 24680484
TI  - Long-term survival after isolated tricuspid valve replacement.
AB  - BACKGROUND: Isolated replacement of the tricuspid valve is rare, and the decision
      to operate is difficult. This study reviews the in-hospital mortality and long
      term survival after tricuspid valve replacement in the absence of concomitant
      left sided valve surgery. It identifies predictors of poor outcome. METHODS: All
      patients who underwent tricuspid valve replacement between January 1995 and
      December 2011 were retrospectively reviewed. Patients having concomitant mitral
      or aortic valve surgery were excluded. Logistic regression was used to identify
      predictors of early and late death. RESULTS: Twenty-nine cases were identified.
      There were six in-hospital deaths (20.6%), and eight late deaths. Ascites was
      associated with in-hospital death (hazard ratio 16.96; p=0.0052). Higher dose of
      Frusemide was associated with late mortality (hazard ratio 1.157 per 20mg
      increase; p=0.0155). Frusemide dose and ascites were both significantly
      associated with death overall (p<0.01). Survival analysis estimated a 50%
      probability of surviving to 12.45 years. CONCLUSIONS: Isolated tricuspid valve
      replacement has a high peri-operative risk. Long-term survival in this study was
      consistent with other reports. Ascites and higher doses of Frusemide were
      associated with poor outcomes.

PMID- 24680485
TI  - Endothelial progenitor cells and pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease characterised by
      lung endothelial cell dysfunction and vascular remodelling. A number of studies
      now suggest that endothelial progenitor cells (EPCs) may induce
      neovascularisation and could be a promising approach for cell based therapy for
      PAH. On the contrary EPCs may contribute to pulmonary vascular remodelling,
      particularly in end-stage pulmonary disease. This review article will provide a
      brief summary of the relationship between PAH and EPCs, the application of the
      EPCs to PAH and highlight the potential clinical application of the EPCs cell
      therapy to PAH. 

PMID- 24680486
TI  - Why the confusion about sinus headache?
AB  - Patients often believe they have a sinus headache when in fact the headache
      frequently has another cause. The diagnosis of sinus headache can be confusing
      because of signs and symptoms in common with migraine. Although not as common a
      diagnosis as migraine, sinus headache and the associated treatments can be found
      extensively in references on the Internet. 

PMID- 24680487
TI  - Diagnosing and understanding adult headache.
AB  - Primary headaches are the most common headache disorders. The most common forms
      are tension-type headaches, migraine, and cluster headache. Knowing the clinical
      presentation coupled with taking a thorough history taking and performing a
      thorough physical examination usually helps in arriving at a correct diagnosis.
      Special attention should be paid to unusual clinical presentations. Further
      diagnostic work-up should be performed in the presence of atypical and worrisome
      signs. 

PMID- 24680488
TI  - Imaging for headache: what the otolaryngologist looks for.
AB  - Diagnosing a rhinogenic cause of headache or facial pain outside of the classic
      definitions of chronic, acute, and subacute sinusitis can be challenging for the
      practicing otolaryngologist. Contact-point headaches have been clinically
      characterized as causing facial pain secondary to abutting mucosal contact from
      the lateral nasal wall to the septum. Imaging landmarks may help identify these
      potential contact points radiographically through revealing anatomic variants
      such as septal spurs and abnormally large lateral nasal structures. However,
      other potential rhinologic sources, such as barosinusitis, recurrent barotrauma,
      or recurrent acute sinusitis occurring between active episodes, are challenging
      to identify through hallmark imaging findings. 

PMID- 24680489
TI  - Imaging for headache: what the neuroradiologist looks for.
AB  - In this article, computed tomography and magnetic resonance imaging anatomy and
      pathology of sinus disease is discussed, specifically relating to facial pain,
      rhinogenic headache, and sinus outflow obstruction. Findings commonly seen in
      acute, chronic, infectious, and inflammatory sinusitis are illustrated, with
      additional examples of secondary intracranial and orbital involvement, and more
      aggressive infectious and neoplastic processes. 

PMID- 24680490
TI  - Medical management of adult headache.
AB  - We review the therapies for primary headache disorders: migraine, chronic
      migraine, tension-type headache, and cluster headache. Recommendations follow the
      evidence-based treatments so far as is possible with expert opinion to give
      clinical guidance. Headache has 2 levels of care: acute treatments designed to
      stop a headache from progressing and alleviate all symptoms associated with the
      headache and preventive therapies for patients whose headache frequency is such
      that by itself produces significant disability and impact on quality of life, or
      where the frequency of use of acute medications, regardless of efficacy, poses
      risks in terms of overuse or adverse events. 

PMID- 24680491
TI  - What the nonneurologist can do to treat headache.
AB  - Nonneurologists who treat patients with headaches should be able recognize common
      headache types and to initiate therapy for tension-type headaches and migraines.
      Patients with complicated headache scenarios should be referred to a neurologist
      for consultation. 

PMID- 24680492
TI  - What do we know about rhinogenic headache? The otolaryngologist's challenge.
AB  - Sinus headache is a common presenting complaint in the otolaryngology office.
      Although most patients with this presentation are found to have migraine
      headache, many do not, and others fail therapy. This review focuses on the
      current understanding of nonneoplastic rhinogenic headache: headaches that are
      caused or exacerbated by nasal or paranasal sinus disease or anatomy. The
      literature regarding this topic is reviewed, along with a review of surgical
      series seeking to correct these abnormalities and the outcomes obtained with
      intervention. Suggestions are provided regarding patient diagnosis and
      management, and options for intervention are reviewed. 

PMID- 24680493
TI  - The otolaryngologist's challenge: the differential diagnosis of the positive
      scan.

PMID- 24680495
TI  - Red flags and comfort signs for ominous secondary headaches.
AB  - Secondary headaches are classified by the cause of the underlying disease process
      that is causing the headache. There are hundreds of secondary headache diagnoses
      and this article is not an exhaustive discussion of secondary headache disorders.
      Maintaining a high level of virulence and having a structured approach to
      evaluating all patients with headache is the key to timely diagnosis of secondary
      headache disorders. Diagnostic testing is indicated based on the suspected
      disorder and management is determined by treatment of the underlying disease
      causing the headache. 

PMID- 24680494
TI  - Evaluation and management of "sinus headache" in the otolaryngology practice.
AB  - Patients, primary care doctors, neurologists and otolaryngologists often have
      differing views on what is truly causing headache in the sinonasal region. This
      review discusses common primary headache diagnoses that can masquerade as "sinus
      headache" or "rhinogenic headache," such as migraine, trigeminal neuralgia,
      tension-type headache, temporomandibular joint dysfunction, giant cell arteritis
      (also known as temporal arteritis) and medication overuse headache, as well as
      the trigeminal autonomic cephalalgias, including cluster headache, paroxysmal
      hemicrania, and hemicrania continua. Diagnostic criteria are discussed and
      evidence outlined that allows physicians to make better clinical diagnoses and
      point patients toward better treatment options. 

PMID- 24680496
TI  - The essential role of the otolaryngologist in the diagnosis and management of
      temporomandibular joint and chronic oral, head, and facial pain disorders.
AB  - This article clarifies the current state of knowledge of chronic oral, head, and
      facial pain (COHFP) conditions with the inclusion of temporomandibular joint
      disorders as just one component of the variety of conditions that can cause head
      and facial pain. Obtaining an accurate diagnosis in a timely manner is extremely
      important because COHFP symptoms can be caused by a variety of pathologic
      conditions that can be inflammatory, degenerative, neurologic, neoplastic, or
      systemic in origin. The essential role of the specialty of otolaryngology in the
      diagnosis and management of patients with these complex COHFP conditions is
      emphasized. 

PMID- 24680497
TI  - Vertiginous headache and its management.
AB  - Vertiginous headache encompasses patients with dizziness or vertigo as well as
      headache, even though the symptoms may not occur in an obvious temporal
      relationship. The type of dizziness experienced by patients is different from the
      heavy-headedness experienced during rhinogenic headache. Patients may have a
      personal or family history of typical or atypical migraine. They should be
      evaluated for possible Meniere syndrome, migraine headaches, and/or eye movement
      disorders. Management is directed to treatment of the underlying abnormality.
      Long-term follow-up of these patients is necessary, because further otologic
      abnormalities may present later. 

PMID- 24680498
TI  - The neurosurgical treatment of neuropathic facial pain.
AB  - This article reviews the definition, etiology and evaluation, and medical and
      neurosurgical treatment of neuropathic facial pain. A neuropathic origin for
      facial pain should be considered when evaluating a patient for rhinologic surgery
      because of complaints of facial pain. Neuropathic facial pain is caused by
      vascular compression of the trigeminal nerve in the prepontine cistern and is
      characterized by an intermittent prickling or stabbing component or a constant
      burning, searing pain. Medical treatment consists of anticonvulsant medication.
      Neurosurgical treatment may require microvascular decompression of the trigeminal
      nerve. 

PMID- 24680499
TI  - Headache in otolaryngology: rhinogenic and beyond.

PMID- 24680500
TI  - Malabsorption and malabsorption tests: do they still matter?

PMID- 24680501
TI  - Functional analysis of c-di-AMP phosphodiesterase, GdpP, in Streptococcus suis
      serotype 2.
AB  - Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes
      serious diseases in pigs and humans. GdpP protein is a recently discovered
      specific phosphodiesterase that degrades cyclic diadenosine monophosphate (c-di
      AMP). It is widely distributed among the firmicutes phylum and altered expression
      of GdpP is associated with several phenotypes in various bacterial strains. We
      investigated the role of GdpP in physiology and virulence in SS2. An in-frame
      mutant of gdpP was constructed using homologous recombination and bacterial
      growth, biofilm formation, hemolytic activity, cell adherence and invasion,
      expression of virulence factors, and virulence were evaluated. Disruption of gdpP
      increased intracellular c-di-AMP level and affected growth and increased biofilm
      formation of SS2. Simultaneously, the gdpP mutant strain exhibited a significant
      decrease in hemolytic activity and adherence to and invasion of HEp-2 cells
      compared with the parental strain. Quantitative reverse transcriptase polymerase
      chain reaction indicated significantly reduced expression of the known virulence
      genes cps2, sly, fpbs, mrp, ef and gdh in the gdpP mutant. In murine infection
      models, the gdpP mutant strain was attenuated, and impaired bacterial growth was
      observed in specific organs. All these findings revealed a significant
      contribution of gdpP and its substrate (c-di-AMP) to the biology and virulence of
      SS2. 

PMID- 24680503
TI  - Expansion of coverage of Carbohydrate Structure Database (CSDB).
AB  - The Bacterial Carbohydrate Structure Database (BCSDB), which has been maintained
      since 2005, was expanded to cover glycans from plants and fungi. The current
      coverage on plant and fungal glycans includes several thousands of the CarbBank
      records, as well as data published before 1996 but not deposited in CarbBank.
      Prior to deposition, the data were verified against the original publications and
      supplemented with additional information, such as NMR spectra. Both the Bacterial
      and Plant and Fungal Carbohydrate Structure Databases are freely available at
      http://csdb.glycoscience.ru. 

PMID- 24680502
TI  - Association of age at depression onset with cognitive functioning in individuals
      with late-life depression and executive dysfunction.
AB  - OBJECTIVE: To compare patterns of cognitive performance in older adults with late
      onset depression (LOD; >=65 years of age) with that of older adults with early
      onset depression (EOD; <65 years). METHODS: Participants were 171 adults aged 60
      years or older with major depression and executive dysfunction who were
      participating in a randomized psychotherapy trial. Participants included 72 LOD
      and 99 EOD individuals. Cognitive performance on measures of verbal learning,
      memory, and executive functioning were evaluated. Demographic and clinical
      characteristics, severity of cerebrovascular risk factors, and disability ratings
      were also compared between groups. RESULTS: The LOD group was older and had fewer
      previous episodes of depression and lower severity of depression compared with
      EOD participants. The LOD group demonstrated poorer performance on measures of
      verbal learning (F(1,161) = 4.28, p = 0.04) and memory (F(1,160) = 4.65, p =
      0.03) than the EOD group. Linear regression analysis demonstrated that LOD and
      fewer years of education were significant predictors of poorer verbal learning
      (F(7,114) = 6.25, p <0.001) and memory (F(7,113)=7.24, p <0.001). Performance on
      measures of executive functioning, severity of vascular risk factors, and
      disability ratings did not differ between the two groups. CONCLUSION: In older
      adults with depression and executive dysfunction, LOD was associated with poorer
      performance on measures of verbal learning and memory. Aging-related brain
      changes associated with LOD may play a more important role, leading to
      dysfunction in these cognitive domains than a history of recurrent depressive
      episodes in older adults with a dysexecutive syndrome.

PMID- 24680504
TI  - Chemical and enzymatic methodologies for the synthesis of enantiomerically pure
      glyceraldehyde 3-phosphates.
AB  - Glyceraldehyde 3-phosphates are important intermediates of many central metabolic
      pathways in a large number of living organisms. d-Glyceraldehyde 3-phosphate (d
      GAP) is a key intermediate during glycolysis and can as well be found in a
      variety of other metabolic pathways. The opposite enantiomer, l-glyceraldehyde 3
      phosphate (l-GAP), has been found in a few exciting new pathways. Here, improved
      syntheses of enantiomerically pure glyceraldehyde 3-phosphates are reported.
      While d-GAP was synthesized by periodate cleavage of d-fructose 6-phosphate, l
      GAP was obtained by enzymatic phosphorylation of l-glyceraldehyde. (1)H- and
      (31)P NMR spectroscopy was applied in order to examine pH-dependent behavior of
      GAP over time and to identify potential degradation products. It was found that
      GAP is stable in acidic aqueous solution below pH 4. At pH 7, methylglyoxal is
      formed, whereas under alkaline conditions, the formation of lactic acid could be
      observed. 

PMID- 24680505
TI  - Preparation of new type of organocatalysts having a carbohydrate scaffold.
AB  - The synthesis of nine new, bifunctional organocatalysts having carbohydrate
      scaffolds has been accomplished. In these catalysts both of the catalytic amino
      and thiourea functions are directly attached to a carbohydrate core. The
      activities of the newly prepared catalysts were tested in a Michael addition. 

PMID- 24680507
TI  - Structural investigation of rhamnose-rich polysaccharides from Streptococcus
      dysgalactiae bovine mastitis isolate.
AB  - Different rhamnose-rich polysaccharides (RRP) were identified in the cell
      envelope of the Gram-positive bovine mastitis isolate Streptococcus dysgalactiae
      2023. Structural investigations of the 1D and 2D nuclear magnetic resonance
      experiments as well as chemical analyses identified as main components l-Rha and
      d-GalNAc. Two main RRP were characterized, namely 1 being composed of the
      repeating unit {->3)-alpha-l-Rhap-(1->2)-[alpha-d-GalpNAc-(1->3)-beta-d-GalpNAc
      (1->3)-]alpha-l-Rhap-(1} and 2 possessing the repeat [->2)-alpha-l-Rhap-(1->3)
      alpha-l-Rhap-(1->]. 

PMID- 24680506
TI  - Conformational changes of 1-4-glucopyranosyl residues of a sulfated C-C linked
      hexasaccharide.
AB  - This work describes the structure of a fully sulfated maltotriose alpha-beta C-C
      linked dimer, where a central glycosidic bond was substituted by a non natural,
      hydrolase-resistant C-C bond. Such compound shows anti-metastatic properties
      being an inhibitor of the heparanase enzymatic activity and of P-selectin
      mediated cell-cell interactions. NMR spectroscopy was applied to investigate the
      structure and conformational properties of this C-C linked hexasaccharide. The
      presence of sulfate substituents and the internal C-C bond drives the two
      internal rings in an unusual (1)C(4) chair conformation, while the external rings
      linked by glycosidic bonds retain the typical (4)C(1) conformation. The NMR
      results were confirmed by molecular mechanics calculations using structure
      corresponding di- and tetrasaccharides as models.

PMID- 24680508
TI  - N-Bridged 1-deoxynojirimycin dimers as selective insect trehalase inhibitors.
AB  - A small set of N-bridged 1-deoxynojirimycin dimers has been synthesized and
      evaluated as potential inhibitors of insect trehalase from midge larvae of
      Chironomus riparius, porcine trehalase as the mammalian counterpart and alpha
      amylase from human saliva. All the tested compounds (2-4) proved to be active
      (micromolar range activity) against insect trehalase, showing selectivity toward
      the insect glycosidase. No activity was observed against alpha-amylase. 

PMID- 24680509
TI  - Sialo-CEST: chemical exchange saturation transfer NMR of oligo- and poly-sialic
      acids and the assignment of their hydroxyl groups using selective- and HSQC
      TOCSY.
AB  - Chemical exchange saturation transfer (CEST) is an NMR method that takes
      advantage of proton exchange between solute and solvent molecules in dynamic
      equilibrium, enabling the detection of the solute NMR signals with enhanced
      sensitivity. Herein, we report that the hydroxyl groups in a naturally occurring
      polysaccharide, alpha-2,8 polysialic acid in aqueous solution, yield very
      significant CEST effects even at 37 degrees C where the resonances of the
      hydroxyl groups are not directly observed. We also report the assignments of the
      hydroxyl groups for the polymer and its oligomeric building blocks, from monomer
      to hexamer. We show that the same assignments can be made by either (1)H-(1)H
      TOCSY methods or (1)H-(13)C HSQC-TOCSY methods, to alleviate spectral overlap.
      Finally, we report the exchange rates of the OH groups with water and show how
      these rates can be used to select and fine-tune CEST effects. 

PMID- 24680510
TI  - Synthesis and biological evaluation of arabinose 5-phosphate mimics modified at
      position five.
AB  - A set of new metabolically stable arabinose 5-phosphate analogues possessing
      phosphate mimetic groups at position 5 was synthesised. Their ability to interact
      with arabinose 5-phosphate isomerase from Pseudomonas aeruginosa was evaluated by
      STD-NMR studies. The synthesised compounds were also characterised for their
      activity in vivo on P. aeruginosa and Escherichia coli strains. Unfortunately,
      none of the synthesised compounds was able neither to bind API nor to inhibit
      bacterial growth. 

PMID- 24680511
TI  - Campylobacter jejuni strain discrimination and temperature-dependent glycome
      expression profiling by lectin microarray.
AB  - Gram-negative Campylobacter jejuni is the leading cause of bacterial
      gastroenteritis in humans worldwide and the most frequently identified infectious
      trigger in patients developing Guillain-Barre syndrome (GBS). While C. jejuni is
      pathogenic in humans, it is a commensal in avian hosts. Bacterial cell surface
      carbohydrates are important virulence factors and play roles in adherence,
      colonisation and infection. The mechanisms leading to infection or persistent
      colonisation of C. jejuni are not well understood but host temperature may
      provide an important stimulus for specific adaptation. Thus, examination of the
      modulation of the total surface glycome of C. jejuni in response to temperature
      may help shed light on commensal and pathogenic mechanisms for this species. C.
      jejuni strains 81116 and 81-176 were cultured at 37 and 42 degrees C to simulate
      human and avian host conditions, respectively, and whole cells were profiled on
      lectin microarrays constructed to include a wide range of binding specificities.
      C. jejuni 81116 profiles indicated that the previously characterised
      lipopolysaccharide (LPS)-like molecule and N-linked glycans were the
      predominantly recognised cell surface structures while capsular polysaccharide
      (CPS), lipooligosaccharides (LOS) and N-linked glycosylation were best recognised
      for strain 81-176 at 37 degrees C. The profiles of both strains varied and were
      distinguishable at both temperatures. At the higher temperature, reduced
      dominance of the LPS-like structure was associated with strain 81116 and a change
      in the relative distribution of CPS and LOS structures was indicated for strain
      81-176. This change in LOS molecular mass species distribution between
      temperatures was confirmed by SDS-PAGE analysis. Additionally, opposite behaviour
      of certain lectins was noted between the plate agglutination assay and the
      microarray platform. Insights into the important glycosylation involved in C.
      jejuni host cell tropism at different growth temperatures were gained using the
      lectin microarray platform. 

PMID- 24680512
TI  - Glycans in immune recognition and response.
AB  - Glycans at the forefront of cells facilitate immune recognition processes. Cancer
      cells commonly present altered cell surface glycosylation, especially manifested
      in the expression of sialic acid at the termini of glycolipids and glycoproteins.
      Although tumor-associated carbohydrate antigens (TACAs) result in expression of
      altered-self, most such carbohydrates do not elicit strong humoral responses.
      Various strategies had been devised to elicit increased immunogenicity of such
      TACA aiming for potent immunotherapeutic antibodies or cancer vaccines. However
      some carbohydrates are immunogenic in humans and hold potential for novel
      glycotherapies. N-Glycolylneuraminic acid (Neu5Gc) is a foreign immunogenic sugar
      in humans originating from the diet (e.g., red meat) and subsequently expressed
      on the cell surface, especially accumulating on carcinoma. Consequently, the
      human immune system detects this non-self carbohydrate generating a broad anti
      Neu5Gc antibody response. The co-existence of Neu5Gc/anti-Neu5Gc within humans
      spurs chronic inflammation mediated disease, including cancer. Concurrently, anti
      Neu5Gc antibodies hold potential for novel targeted therapy. alphaGal is another
      foreign immunogenic carbohydrate antigen in humans and all humans have
      circulating anti-Gal antibodies. This review aims to describe the immunogenicity
      of Neu5Gc and its implications for human diseases, highlighting differences and
      similarities with alphaGal and its potential for novel targeted theranostics. 

PMID- 24680513
TI  - Comparison of separation techniques for the elucidation of IgG N-glycans pooled
      from healthy mammalian species.
AB  - The IgG N-glycome provides sufficient complexity and information content to serve
      as an excellent source for biomarker discovery in mammalian health. Since
      oligosaccharides play a significant role in many biological processes it is very
      important to understand their structure. The glycosylation is cell type specific
      as well as highly variable depending on the species producing the IgG. We
      evaluated the variation of N-linked glycosylation of human, bovine, ovine,
      equine, canine and feline IgG using three orthogonal glycan separation
      techniques: hydrophilic interaction liquid chromatography (HILIC)-UPLC, reversed
      phase (RP)-UPLC and capillary electrophoresis with laser induced fluorescence
      detection (CE-LIF). The separation of the glycans by these high resolution
      methods yielded different profiles due to diverse chemistries. However, the %
      abundance of structures obtained by CE-LIF and HILIC-UPLC were similar, whereas
      the analysis by RP-UPLC was difficult to compare as the structures were separated
      by classes of glycans (highly mannosylated, fucosylated, bisected, fucosylated
      and bisected) resulting in the co-elution of many structures. The IgGs from
      various species were selected due to the complexity and variation in their N
      glycan composition thereby highlighting the complementarity of these separation
      techniques. 

PMID- 24680514
TI  - Chemoenzymatic synthesis of sialosides containing C7-modified sialic acids and
      their application in sialidase substrate specificity studies.
AB  - Modifications at the glycerol side chain of sialic acid in sialosides modulate
      their recognition by sialic acid-binding proteins and sialidases. However,
      limited work has been focused on the synthesis and functional studies of
      sialosides with C7-modified sialic acids. Here we report chemical synthesis of C4
      modified ManNAc and mannose and their application as sialic acid precursors in a
      highly efficient one-pot three-enzyme system for chemoenzymatic synthesis of
      alpha2-3- and alpha2-6-linked sialyl para-nitrophenyl galactosides in which the
      C7-hydroxyl group in sialic acid (N-acetylneuraminic acid, Neu5Ac, or 2-keto-3
      deoxynonulosonic acid, Kdn) was systematically substituted by -F, -OMe, -H, and 
      N3 groups. Substrate specificity study of bacterial and human sialidases using
      the obtained sialoside library containing C7-modified sialic acids showed that
      sialosides containing C7-deoxy Neu5Ac were selective substrates for all bacterial
      sialidases tested but not for human NEU2. The information obtained from sialidase
      substrate specificity can be used to guide the design of new inhibitors that are
      selective against bacterial sialidases. 

PMID- 24680515
TI  - A transitional hydrolase to glycosynthase mutant by Glu to Asp substitution at
      the catalytic nucleophile in a retaining glycosidase.
AB  - Glycosynthases from more than 16 glycosidase families have been developed for the
      efficient synthesis of oligosaccharides and glycoconjugates. beta-1,3-1,4-Glucan
      oligo- and polysaccharides with defined sequences can be quantitatively achieved
      with the glycosynthases derived from Bacillus licheniformis beta-1,3-1,4
      glucanase. The screening of a nucleophile saturation library of this enzyme
      yielded the unexpected E134D mutant which has high glycosynthase efficiency (25%
      higher kcat than the best glycosynthase to date, E134S) but also retains some
      hydrolase activity (2% relative to the wild-type enzyme). Here, we report the
      biochemical and structural analyses of this mutant compared to E134S and wild
      type enzymes. E134D shows a pH profile of general base catalysis for the
      glycosynthase activity, with a kinetic pKa (on kcat/KM) assigned to Glu138 of
      5.8, whereas the same residue acts as a general acid in the hydrolase activity
      with the same pKa value. The pKa of Glu138 in the wt enzyme was 7.0, a high value
      due to the presence of the catalytic nucleophile Glu134 which destabilizes the
      conjugate base of Glu138. Thus, the pKa of Glu138 drops 1.1 pH units in the
      mutant relative to the wild-type enzyme meaning that the larger distance between
      carboxylates in positions 138 and 134 (5.6A for wt, 7.0A for E134D) and/or a new
      hydrogen bonding interaction with a third Asp residue (Asp136) in the mutant
      reduces the effect of the negatively charged Asp134. In consequence, the pKa of
      Glu138 has a similar pKa value in the E134D mutant than in the other
      glycosynthase mutants having a neutral residue in position 134. The behavior of
      the E134D mutant shows that shortening the side chain of the nucleophile, despite
      maintaining a carboxylate group, confers glycosynthase activity. Therefore E134D
      is a transitional hydrolase to glycosynthase mutation. 

PMID- 24680517
TI  - Corneal incisions with femtosecond lasers.

PMID- 24680516
TI  - The majority of sialylated glycoproteins in adult Ixodes ricinus ticks originate
      in the host, not the tick.
AB  - The presence of sialylated structures in tick organs was observed previously
      using lectin staining. Recently, we demonstrated the presence of sialylated N
      glycans using mass spectrometry in tick salivary glands and the gut. However, we
      proposed a host (blood) origin for these glycans and mapped the transport of
      sialylated molecules from the gut to the salivary glands. In this report, we
      performed quantitation of whole sialic acid and of metabolically incorporated
      sialic acid (N-azido neuraminic acid) in Ixodes ricinus tick samples. We show
      that the majority of sialylated molecules in the adult tick originate in the host
      (blood) and are not synthesized by the tick. Similar results were observed for
      tick cell cultures. The almost complete absence of tick sialylated molecules and
      the specific transport and localization of host structures into the tick salivary
      glands and the saliva raises many questions on the role of these molecules in the
      physiology and, specifically, the blood-feeding of ticks. 

PMID- 24680518
TI  - Morphologic study of the cornea by in vivo confocal microscopy and optical
      coherence tomography after bifocal refractive corneal inlay implantation.
AB  - PURPOSE: To evaluate the biocompatibility of the Flexivue Microlens intracorneal
      inlay based on healing of corneal wounds and analysis of corneal structural
      features using in vivo confocal microscopy (IVCM) and anterior segment optical
      coherence tomography (AS-OCT). SETTING: Ophthalmology Department, Misericordia e
      Dolce Hospital, Prato, Italy. DESIGN: Case series. METHODS: The intracorneal
      inlay was inserted in a stromal pocket created in the nondominant eye of
      emmetropic presbyopic patients using a femtosecond laser. In vivo confocal
      microscopy and AS-OCT examinations were performed preoperatively and 1, 6, and 12
      months postoperatively. RESULTS: The mean follow-up was 7.6 months. In the early
      postoperative period, IVCM showed intense cellular activity in the stroma around
      the inlay, edema, inflammation, and degenerative material deposition but normal
      regularity after 12 months. Anterior segment OCT showed a regular planar shape of
      the corneal pocket in all eyes. The mean of the side-cut angles was 30.7 degrees.
      The mean difference between the measured and planned pocket depth was 9.77 MUm.
      At 1 month, hyperreflective areas beneath the inlay and microfolds were observed
      in 21 of the 52 eyes. After 12 months, the anterior segment profile was regular
      and interface pocket reflectivity decreased over time. Six patients had inlay
      removal postoperatively (3 before 6 months; 3 before 12 months); after removal,
      IVCM and AS-OCT showed clear corneas without signs of irregularity. CONCLUSION:
      In vivo confocal microscopy and AS-OCT analysis showed that the inlay elicited a
      low-level wound-healing response in its immediate vicinity with no alteration in
      the corneal structures. FINANCIAL DISCLOSURE: Dr. M. Fantozzi is a member of the
      Presbia medical advisory board. No other author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24680519
TI  - Comparative evaluation of dual Scheimpflug imaging parameters in keratoconus,
      early keratoconus, and normal eyes.
AB  - PURPOSE: To determine the efficacy of various parameters measured by dual
      Scheimpflug imaging technology in differentiating eyes with keratoconus or early
      keratoconus from normal eyes. SETTING: Cornea Service, Wills Eye Institute,
      Philadelphia, Pennsylvania, USA. DESIGN: Comparative case series. METHODS: A
      retrospective evaluation was performed of the parameters provided by the Galilei
      dual Scheimpflug analyzer in keratoconus, early keratoconus, and normal eyes.
      Logistic regression and receiver operating characteristic curve analysis were
      used to compare the mean values and to calculate the sensitivity and specificity
      of these parameters. RESULTS: Many parameters were statistically significantly
      different between keratoconus and normal eyes compared with early keratoconus
      eyes (P<.05). Total cornea power-steep and posterior curvature-steep keratometry
      had the highest area under the curve (AUC) score (0.99) for differentiating
      keratoconus eyes from normal eyes. All anterior curvature parameters were
      statistically significant in differentiating keratoconus eyes from normal eyes,
      whereas only the anterior curvature-steep was statistically significant in
      differentiating early keratoconus eyes from normal eyes. The central pachymetry
      and thinnest pachymetry were statistically significant in differentiating
      keratoconus and early keratoconus eyes from normal eyes. Third-order root mean
      square (RMS) and total RMS had the highest AUC scores (0.83 and 0.82,
      respectively) for differentiating early keratoconus eyes from normal eyes.
      CONCLUSION: Total corneal power, anterior curvature, posterior curvature,
      pachymetry, and corneal aberration data generated from the dual Scheimpflug
      analyzer showed promising results in differentiating keratoconus and early
      keratoconus eyes from normal eyes. FINANCIAL DISCLOSURE: No author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 24680520
TI  - Biometry and intraocular lens power calculation results with a new optical
      biometry device: comparison with the gold standard.
AB  - PURPOSE: To evaluate the agreement in axial length (AL), keratometry (K),
      anterior chamber depth (ACD) measurements; intraocular lens (IOL) power
      calculations; and predictability using a new partial coherence interferometry
      (PCI) optical biometer (AL-Scan) and a reference (gold standard) PCI optical
      biometer (IOLMaster 500). SETTING: Service d'Ophtalmologie, Hopital Bicetre, APHP
      Universite, Paris, France. DESIGN: Evaluation of a diagnostic device. METHODS:
      One eye of consecutive patients scheduled for cataract surgery was measured.
      Biometry was performed with the new biometer and the reference biometer.
      Comparisons were performed for AL, average K at 2.4 mm, ACD, IOL power
      calculations with the Haigis and SRK/T formulas, and postoperative predictability
      of the devices. A P value less than 0.05 was statistically significant. RESULTS:
      The study enrolled 50 patients (mean age 72.6 years+/-4.2 SEM). There was a good
      correlation between biometers for AL, K, and ACD measurements (r=0.999, r=0.933,
      and r=0.701, respectively) and between IOL power calculation with the Haigis
      formula (r=0.972) and the SRK/T formula (r=0.981). The mean absolute error (MAE)
      in IOL power prediction was 0.42+/-0.08 diopter (D) with the new biometer and
      0.44+/-0.08 D with the reference biometer. The MAE was 0.20 D with the Haigis
      formula and 0.19 with the SRK/T formula (P=.36). CONCLUSION: The new PCI biometer
      provided valid measurements compared with the current gold standard, indicating
      that the new device can be used for IOL power calculations for routine cataract
      surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
      in any material or method mentioned.

PMID- 24680521
TI  - In vitro examination of surface light scattering in hydrophobic acrylic
      intraocular lenses.
AB  - PURPOSE: To evaluate laboratory models using accelerated aging to assess surface
      light scattering in hydrophobic acrylic intraocular lenses (IOLs). SETTING:
      Miyata Eye Hospital, Miyazaki, Japan. DESIGN: Experimental study. METHODS:
      Acrysof SA60AT IOLs manufactured before optimization of the IOL production
      process (non-optimized IOLs) and Acrysof SN60WF IOLs that were manufactured after
      optimization of the production process (optimized IOLs) were examined. After the
      IOLs were accelerated aged corresponding to 0, 3, 5, 10, 15, and 20 years,
      surface light scattering was measured with a Scheimpflug camera. Formation of
      water aggregates below the IOL surface was observed with cryogenic focused ion
      beam scanning electron microscopy. RESULTS: In the non-optimized IOLs, surface
      light scattering increased with aging (P<.001, R2=0.87). There was no significant
      increase in surface light scattering in the optimized IOLs. An increase in water
      aggregates with sizes of nanometer order was observed in the aged non-optimized
      IOLs. CONCLUSIONS: An in vitro model using accelerated aging was effective for
      examining the incidence of surface light scattering. The laboratory results
      showed suppression of surface light scattering in the IOL manufactured with the
      optimized process. FINANCIAL DISCLOSURE: No author has a financial or proprietary
      interest in any material or method mentioned.

PMID- 24680522
TI  - Incomplete capsulotomy using femtosecond laser with a pupil expansion device.

PMID- 24680523
TI  - Anterior Chamber Surgical Problem: April consultation #1.

PMID- 24680524
TI  - April consultation #2.

PMID- 24680525
TI  - April consultation #3.

PMID- 24680526
TI  - April consultation #4.

PMID- 24680527
TI  - April consultation #5.

PMID- 24680528
TI  - April consultation #6.

PMID- 24680529
TI  - Reply: To PMID 23988244.

PMID- 24680530
TI  - Endophthalmitis in Europe: data collection conundrum.

PMID- 24680531
TI  - Endophthalmitis in Spain: more than meets the eye?

PMID- 24680532
TI  - Comments on surgical iridotomy technique.

PMID- 24680533
TI  - Comments on surgical iridotomy technique.

PMID- 24680534
TI  - Reply: Comments on surgical iridotomy technique.

PMID- 24680535
TI  - Reply: To PMID 24075156.

PMID- 24680536
TI  - Intracameral triamcinolone acetonide in phacotrabeculectomy.

PMID- 24680537
TI  - Reply: To PMID 24160382.

PMID- 24680538
TI  - Hydrodissection techniques during femtosecond laser-assisted cataract surgery.

PMID- 24680539
TI  - Reply: To PMID 24269138.

PMID- 24680540
TI  - Decadal land cover change dynamics in Bhutan.
AB  - Land cover (LC) is one of the most important and easily detectable indicators of
      change in ecosystem services and livelihood support systems. This paper describes
      the decadal dynamics in LC changes at national and sub-national level in Bhutan
      derived by applying object-based image analysis (OBIA) techniques to 1990, 2000,
      and 2010 Landsat (30 m spatial resolution) data. Ten LC classes were defined in
      order to give a harmonized legend land cover classification system (LCCS). An
      accuracy of 83% was achieved for LC-2010 as determined from spot analysis using
      very high resolution satellite data from Google Earth Pro and limited field
      verification. At the national level, overall forest increased from 25,558 to
      26,732 km(2) between 1990 and 2010, equivalent to an average annual growth rate
      of 59 km(2)/year (0.22%). There was an overall reduction in grassland, shrubland,
      and barren area, but the observations were highly dependent on time of
      acquisition of the satellite data and climatic conditions. The greatest change
      from non-forest to forest (277 km(2)) was in Bumthang district, followed by
      Wangdue Phodrang and Trashigang, with the least (1 km(2)) in Tsirang. Forest and
      scrub forest covers close to 75% of the land area of Bhutan, and just over half
      of the total area (51%) has some form of conservation status. This study
      indicates that numerous applications and analyses can be carried out to support
      improved land cover and land use (LCLU) management. It will be possible to
      replicate this study in the future as comparable new satellite data is scheduled
      to become available. 

PMID- 24680541
TI  - Sensitivity of crop cover to climate variability: insights from two Indian agro
      ecoregions.
AB  - Crop productivity in India varies greatly with inter-annual climate variability
      and is highly dependent on monsoon rainfall and temperature. The sensitivity of
      yields to future climate variability varies with crop type, access to irrigation
      and other biophysical and socio-economic factors. To better understand
      sensitivities to future climate, this study focuses on agro-ecological subregions
      in Central and Western India that span a range of crops, irrigation, biophysical
      conditions and socioeconomic characteristics. Climate variability is derived from
      remotely-sensed data products, Tropical Rainfall Measuring Mission (TRMM -
      precipitation) and Moderate Resolution Imaging Spectroradiometer (MODIS -
      temperature). We examined green-leaf phenologies as proxy for crop productivity
      using the MODIS Enhanced Vegetation Index (EVI) from 2000 to 2012. Using both
      monsoon and winter growing seasons, we assessed phenological sensitivity to inter
      annual variability in precipitation and temperature patterns. Inter-annual EVI
      phenology anomalies ranged from -25% to 25%, with some highly anomalous values up
      to 200%. Monsoon crop phenology in the Central India site is highly sensitive to
      climate, especially the timing of the start and end of the monsoon and intensity
      of precipitation. In the Western India site, monsoon crop phenology is less
      sensitive to precipitation variability, yet shows considerable fluctuations in
      monsoon crop productivity across the years. Temperature is critically important
      for winter productivity across a range of crop and management types, such that
      irrigation might not provide a sufficient buffer against projected temperature
      increases. Better access to weather information and usage of climate-resilient
      crop types would play pivotal role in maintaining future productivity. Effective
      strategies to adapt to projected climate changes in the coming decades would also
      need to be tailored to regional biophysical and socio-economic conditions. 

PMID- 24680542
TI  - Single and multi-component adsorption of salicylic acid, clofibric acid,
      carbamazepine and caffeine from water onto transition metal modified and
      partially calcined inorganic-organic pillared clay fixed beds.
AB  - Fixed-beds of transition metal (Co(2+), Ni(2+) or Cu(2+)) inorganic-organic
      pillared clays (IOCs) were prepared to study single- and multi-component non
      equilibrium adsorption of a set of pharmaceutical and personal care products
      (PPCPs: salicylic acid, clofibric acid, carbamazepine and caffeine) from water.
      Adsorption capacities for single components revealed that the copper(II) IOCs
      have better affinity toward salicylic and clofibric acid. However, multi
      component adsorption tests showed a considerable decrease in adsorption capacity
      for the acids and an unusual selectivity toward carbamazepine depending on the
      transition metal. This was attributed to a combination of competition between
      PPCPs for adsorption sites, adsorbate-adsorbate interactions, and plausible pore
      blocking caused by carbamazepine. The cobalt(II) IOC bed that was partially
      calcined to fractionate the surfactant moiety showcased the best selectivity
      toward caffeine, even during multi-component adsorption. This was due to a
      combination of a mildly hydrophobic surface and interaction between the PPCP and
      cobalt(II). In general, the tests suggest that these IOCs may be a potential
      solution for the removal of PPCPs if employed in a layered-bed configuration, to
      take care of families of adsorbates in a sequence that would produce sharpened
      concentration wavefronts. 

PMID- 24680543
TI  - Monitoring of xenobiotic ligands for human estrogen receptor and aryl hydrocarbon
      receptor in industrial wastewater effluents.
AB  - Industrial wastewater contains a variety of toxic substances, which may severely
      contaminate the aquatic environment if discharged without adequate treatment. In
      this study, effluents from a thin film transistor liquid crystal display
      wastewater treatment plant and the receiving water were analyzed by bioassays and
      liquid chromatography-tandem mass spectrometry to investigate the presence of
      estrogenic compounds, aryl hydrocarbon receptor (AhR) agonists, and
      genotoxicants. Xenobiotic AhR agonists were frequently detected and, in
      particular, strong AhR agonist activity and genotoxicity were found in the
      suspended solids of the aeration tank outflow. The high AhR agonist activity in
      the final effluent (FE) and the downstream river water suggested that the
      treatment plant failed to remove the wastewater-related AhR agonists. In
      contrast, although significant estrogenic potency could be detected in raw
      wastewater or effluents from different treatment processes, the FE and the
      receiving river water exhibited no or weak estrogenicity. Instrumental analysis
      showed that bisphenol A was often detected in water samples. However, the
      investigated estrogenic compounds could only account for a small portion of the
      estrogenicity in the collected samples. Therefore, further investigation is
      necessary to identify the major estrogenic compounds and AhR agonist contaminants
      in the wastewater effluents. 

PMID- 24680544
TI  - [Amyloid goiter in a patient with cystic fibrosis].

PMID- 24680545
TI  - Non-cellulosic polysaccharides from the leaves of small balsam (Impatiens
      parviflora DC.).
AB  - The leaves of the annual plant Impatiens parviflora DC., a herbal medicine in
      Asian countries and invasive in managed forests and natural environments in
      Central Europe, have the potential as a source of bioactive phenolic compounds
      and polysaccharides. Extractives accounted for ~22% of the leaves, whereby, the
      methanolic extract contains mainly caffeic acid, ferulic acid, kaempferol, and
      quercetin derivatives, and 1,2,4-trihydroxynaphthalene-1-O-glucoside. From the
      pre-extracted leaves, non-cellulosic polysaccharides were isolated by a five-step
      extraction procedure using as extractants cold water, 0.05 M EDTA, and DMSO in
      the first three steps, and 1% and 5% NaOH in the last two steps. The isolated
      polysaccharide fractions were characterized by chemical, physicochemical, and
      spectroscopic analyses (FTIR and (1)H NMR). The first three fractions contained
      mainly pectin and the alkali-extracted ones methylglucuronoxylan and
      arabinogalactan. The suggested structural features were confirmed using HSQC NMR
      and COSY experiments for polysaccharides of the EDTA-fraction and the Pronase
      treated 5% NaOH-fraction. The EDTA fraction comprised a pectin with low degree of
      methyl-esterification (DM, 37%) with few rhamnogalacturonan RG I segments bearing
      beta-1,4-galactan as side chains. The alkali-extracted fraction comprised a
      degraded methylglucuronoxylan and type II 3,6-arabinogalactan in about equal
      amounts.

PMID- 24680546
TI  - Insights into enhanced thermostability of a cellulosomal enzyme.
AB  - Improved stability of cellulosomal enzymes is of great significance in order to
      provide efficient degradation of cellulosic derivatives for production of
      biofuels. In previous reports, we created a quadruple mutant of the endoglucanase
      Cel8A from Clostridium thermocellum resulting from a combination of both random
      error-prone PCR and a bioinformatics-based consensus mutagenesis approach. The
      quadruple mutant exhibited an increased half-life of activity by 14-fold at 85
      degrees C with no apparent loss of catalytic activity compared to the wild-type
      form. Connection of the wild-type enzyme to its respective cohesin partner
      conferred increased thermostability, but no increase was observed for the cohesin
      complexed mutant enzyme. The mutant and the wild-type enzymes were integrated
      into divalent chimeric scaffoldins with a family 48 exoglucanase partner, and the
      cellulose-degradation activities of resultant designer cellulosomes were
      examined. Despite the heightened thermostability of the mutant as a free enzyme,
      its substitution for the wild-type endoglucanase within the cellulosome context
      failed to exhibit an improvement in overall degradation of cellulose. 

PMID- 24680547
TI  - The diagnostic accuracy of bedside ocular ultrasonography for the diagnosis of
      retinal detachment: a systematic review and meta-analysis.
AB  - The diagnostic accuracy of emergency department (ED) ocular ultrasonography may
      be sufficient for diagnosing retinal detachment. We systematically reviewed the
      literature to determine the diagnostic accuracy of ED ocular ultrasonography for
      the diagnosis of retinal detachment. This review conformed to the recommendations
      from the Meta-analysis of Observational Studies in Epidemiology statement. An
      experienced medical librarian searched the following databases from their
      inception, without language restrictions: Ovid MEDLINE, PubMed, EMBASE, the
      Cochrane Library, Emergency Medical Abstracts, and Google Scholar. Content
      experts were contacted and bibliographies of relevant studies were reviewed to
      identify additional references. Evidence quality was independently assessed by 2
      investigators using the revised Quality Assessment Tool for Diagnostic Accuracy
      Studies (QUADAS-2). Discrepancies were resolved by consensus or adjudication by a
      third reviewer. Diagnostic test characteristics were summarized and reported with
      95% confidence intervals. Of 7,771 unique citations identified, 78 were selected
      for full-text review, resulting in 4 trials assessed for quality. Agreement
      between authors' QUADAS-2 scoring was good (kappa=0.63). Three trials were deemed
      to have a low risk of bias. They enrolled ED-based patients (N=201) and evaluated
      clinician-performed bedside ocular ultrasonography, using either a 7.5- or 10-MHz
      linear-array probe. Two trials included patients who had retinal detachment from
      trauma. The prevalence of retinal detachment ranged from 15% to 38%. Sensitivity
      and specificity ranged from 97% to 100% and 83% to 100%, respectively. The
      results of the bedside ocular ultrasonography were compared with the reference
      standard of an ophthalmologic evaluation; one trial also included orbital
      computed tomography findings suggestive of retinal detachment. Bedside ocular
      ultrasonography has a high degree of accuracy in identifying retinal detachment,
      according to 3 small prospective investigations. Larger prospective validation of
      these findings would be valuable. 

PMID- 24680548
TI  - Many emergency department patients with severe sepsis and septic shock do not
      meet diagnostic criteria within 3 hours of arrival.
AB  - STUDY OBJECTIVE: Proposed national performance measures for severe sepsis or
      septic shock include interventions within 3 hours of emergency department (ED)
      arrival rather than from time of first meeting diagnostic criteria. We aim to
      determine the percentage of ED patients who first meet criteria greater than 3
      hours after arrival. METHODS: We conducted a retrospective analysis of adult
      patients with severe sepsis or septic shock in 2 EDs (university hospital
      [September 2012 to June 2013] and public trauma center [December 2012 to May
      2013]). Times of ED arrival and first meeting clinical criteria were collected
      for quality assurance programs, which differed between institutions. At the
      university hospital, patients with admission diagnoses consistent with infection
      were included. Clinical presentation was defined as time meeting 2 or more
      systemic inflammatory response syndrome criteria and evidence of end-organ
      dysfunction. At the trauma center, only patients with hospital discharge
      diagnoses consistent with infection were included. Clinical presentation was
      defined by time of end-organ dysfunction. RESULTS: Three hundred seventy-two
      patients met inclusion criteria at the university hospital and 133 at the trauma
      center. Median times from ED arrival to first meeting criteria were 68 minutes
      (interquartile range 34 to 130 minutes) and 31 minutes (interquartile range 8 to
      73 minutes), respectively; 15.3% (95% confidence interval 11.9% to 19.3%) and
      9.8% (95% confidence interval 5.5% to 15.7%) first met criteria greater than 3
      hours from ED arrival, respectively. CONCLUSION: Compliance with a performance
      metric for severe sepsis and septic shock within 3 hours of ED arrival would
      require application of this measure to patients who do not meet diagnostic
      criteria, potentially resulting in unnecessary interventions. Measure developers
      should consider these findings.

PMID- 24680549
TI  - Safety and efficacy of edoxaban in patients undergoing hip fracture surgery.
AB  - INTRODUCTION: Edoxaban is an oral, direct, once-daily factor Xa inhibitor. This
      study evaluated the safety and efficacy of edoxaban compared to subcutaneous
      enoxaparin in Japanese patients undergoing hip fracture surgery. MATERIALS AND
      METHODS: In this multicenter, randomized, open-label, active-comparator, phase 3
      trial, 92 patients were randomized 2:1 to receive edoxaban 30mg once daily (n=62)
      or enoxaparin sodium (enoxaparin) 2000IU (equivalent to 20mg) twice daily (n=30)
      for 11 to 14days. The primary endpoints were the incidence of major or clinically
      relevant non-major (CRNM) bleeding and incidence of any bleeding events (major,
      CRNM, or minor bleeding). Secondary efficacy endpoints included the incidence of
      thromboembolic events, venous thromboembolism-related deaths, and all-cause
      deaths. Additional adverse events were recorded throughout the study. RESULTS: In
      the edoxaban and enoxaparin treatment groups, the incidence of major or CRNM
      bleeding was 3.4% and 6.9%, respectively, while any bleeding event occurred in
      25.4% and 17.2% of patients, respectively. The incidence of thromboembolic events
      was 6.5% in the edoxaban group and 3.7% in the enoxaparin group. All events were
      asymptomatic deep vein thrombosis. The incidence of adverse events was 72.9% and
      82.8% in the edoxaban and enoxaparin groups, respectively. CONCLUSIONS: Compared
      to subcutaneous enoxaparin 2000IU twice daily, oral edoxaban 30mg once daily
      demonstrated similar safety and efficacy in the prevention of thromboembolic
      events in Japanese patients undergoing hip fracture surgery. CLINICAL TRIALS
      REGISTRATION NUMBER: NCT01181141.

PMID- 24680550
TI  - Biodistribution of the recombinant fusion protein linking coagulation factor IX
      with albumin (rIX-FP) in rats.
AB  - INTRODUCTION: The recombinant fusion protein linking coagulation factor IX with
      albumin (rIX-FP) is undergoing clinical trials for prophylaxis and on-demand
      treatment of haemophilia B patients. The aim of this study was to investigate the
      pharmacokinetics, whole-body and knee joint distribution of rIX-FP following
      intravenous administration to rats, compared with a marketed, non-fused rFIX and
      recombinant human albumin. MATERIAL AND METHODS: [(3)H]-rIX-FP, [(3)H]-rFIX or
      [(3)H]-albumin were administered to rats followed by quantitative whole-body
      autoradiography over 24 or 240 hours, and the tissue distribution as well as
      elimination of radioactivity were measured. RESULTS: Elimination of all
      radioactivity derived from the three proteins was shown to occur primarily via
      the urine. The tissue distribution of [(3)H]-rIX-FP and [(3)H]-rFIX (but not of
      [(3)H]-albumin) was comparable, both penetrating predominantly into bone, and
      well-perfused tissues, suggesting that the rIX moiety determines the distribution
      pattern of rIX-FP, while the albumin moity is responsible for the prolonged
      plasma and tissue retention. Detailed knee-joint analysis indicated rapid
      presence of [(3)H]-rIX-FP and [(3)H]-rFIX in synovial and mineralised bone
      tissue, mostly localised to the zone of calcified cartilage. Longest retention
      times were observed in the bone marrow and the endosteum of long bones.
      Intriguingly, [(3)H]-rIX-FP- and [(3)H]-albumin-derived radioactive signals were
      detectable up to 240 hours, while [(3)H]-rFIX-derived radioactivity rapidly
      declined after 1hour post-dosing correlating to the extended plasma half-life of
      [(3)H]-rIX-FP. CONCLUSION: The prolonged plasma and tissue retention of rIX-FP
      achieved by albumin fusion may allow a reduction in dosing frequency leading to
      increased therapeutic compliance and convenience.

PMID- 24680551
TI  - Factors predicting the outcome following medical treatment of mesial temporal
      epilepsy with hippocampal sclerosis.
AB  - PURPOSE: There is a lack of information from South America regarding factors that
      predict the clinical outcomes of patients treated medically for mesial temporal
      lobe epilepsy with hippocampal sclerosis (MTLE-HS). This study was conducted to
      determine which of these factors are the most important. METHODS: This study
      included 110 South American patients with MTLE-HS treated with antiepileptic
      drugs. The factors considered included age, gender, age of epilepsy onset,
      interval between the lesion and the first seizure, central nervous system
      infection, traumatic brain injury, perinatal asphyxia, febrile convulsion,
      history of status epilepticus, types of seizures, site of hippocampal sclerosis
      (HS), extrahippocampal pathology, and electroencephalogram (EEG) abnormalities.
      The patients were divided into two groups based on the response to treatment:
      Group I, seizure free for at least two years; and Group II, not seizure free.
      RESULTS: On the multivariate analysis, the factors associated with a poor
      prognosis in terms of seizure frequency and control following treatment included
      the presence of an early onset of seizure, more than 10 seizures per month before
      treatment, and EEG abnormalities. CONCLUSION: The recognition of risk factors,
      such as early onset of seizures, more than 10 seizures per month before
      treatment, and EEG abnormalities, could lead to the identification of risk groups
      among patients with MTLE-HS and refractory epilepsy, possibly designating these
      individuals as candidates for early epilepsy surgery.

PMID- 24680552
TI  - Syncope, seizure-induced bradycardia and asystole: two cases and review of
      clinical and pathophysiological features.
AB  - Episodes of transient loss of consciousness (TLOC) are commonly due to syncope or
      epileptic seizures. The distinction between both entities on clinical grounds and
      eyewitness accounts can be challenging and is often hampered by similar clinical
      features. We briefly summarize syncope-related symptoms and present the case of a
      female patient who suffered from TLOC episodes due to both reflex syncope and
      epileptic seizures. Seizure-induced syncope is a rare complication particularly
      of non-generalized temporal lobe seizures and may be suspected in people with
      epilepsy who report new semiological features with sudden onset of atonia, TLOC
      and seizure-related falls. We review epidemiological, clinical and
      electroencephalographic aspects of seizure-related asystole and syncope and
      discuss their clinical relevance. The implantation of a cardiac pacemaker appears
      to efficiently prevent seizure-related falls and consecutive injuries and is an
      important treatment option if full seizure-control cannot be achieved in these
      patients. We describe a second case of a patient with refractory temporal lobe
      epilepsy and seizure-related syncope which ceased after the implantation of a
      cardiac pacemaker. 

PMID- 24680553
TI  - Acute postoperative seizures and long-term outcome following pediatric epilepsy
      surgery.
AB  - PURPOSE: Acute post-operative seizures (APOS) after epilepsy surgery, previously
      believed to be benign, are increasingly associated with poor long-term prognosis.
      Prior literature has focused primarily on adult temporal lobe epilepsy. This
      retrospective study aimed to identify the prevalence, prognostic significance and
      risk factors for APOS in pediatric epilepsy surgery at a single center. METHOD:
      Retrospective chart review of all children aged 0-21 years undergoing resective
      surgery for epilepsy between 2009 and 2012 at a single center. APOS were defined
      as seizures within 30 days of resection. Surgical outcome was determined, using a
      minimum of 12 months postoperative follow-up for inclusion. RESULTS: APOS,
      defined as a seizure within 30 days of resection, were identified in 50/112 (44%)
      of patients. APOS were a significant predictor of poor postoperative seizure
      outcome (ILAE 4-6); only 26% of those with APOS had a good outcome (ILAE 1-3),
      compared to 76% without APOS. Timing of postoperative seizure was not correlated
      with outcome. Most (54%) with APOS and good outcome had continued seizures
      between 14-30 days postoperatively. Patients with APOS after temporal (p=0.05)
      and extratemporal (p<0.001) resections had a significantly worse prognosis. APOS
      after hemispherectomy were not associated with a worse prognosis (p=0.22). Key
      risk factors for APOS include lack of ictal EEG lateralization to operated
      hemisphere/side of MRI abnormality. CONCLUSION: This study shows an association
      between APOS and poor outcome in both temporal and extratemporal pediatric
      epilepsy surgery. Findings support the expansion of APOS duration to 30 days.

PMID- 24680554
TI  - Stress-induced cardiomyopathy associated with ipratropium bromide therapy in a
      patient with chronic obstructive pulmonary disease.
AB  - Stress-induced cardiomyopathy, also known as 'broken heart syndrome' or Takotsubo
      cardiomyopathy, is characterized by transient systolic dysfunction of the apical
      and/or mid segments of the left ventricle, in the absence of significant coronary
      artery disease. We report the case of a 56-year-old male patient with chronic
      obstructive pulmonary disease (COPD), with stress-induced cardiomyopathy
      associated with the use of ipratropium bromide, administered in the context of an
      acute exacerbation of COPD. 

PMID- 24680555
TI  - Echocardiographic assessment of right ventricular contractile reserve in patients
      with pulmonary hypertension.
AB  - INTRODUCTION AND AIM: Right ventricular function is a major determinant of
      prognosis in pulmonary hypertension. The aim of this study was to assess and
      compare right ventricular contractile reserve in healthy subjects (controls) and
      in subjects with pulmonary hypertension (cases). METHODS: In this prospective
      study of seven cases and seven controls undergoing treadmill stress
      echocardiography, right ventricular S-wave velocity, tricuspid annular plane
      systolic excursion (TAPSE), right ventricular fractional area change (RVFAC) and
      stroke volume index were assessed at rest and with exercise. The increase in each
      parameter between rest and exercise for cases and controls was analyzed and the
      magnitude of change in each parameter with exercise between cases and controls
      was compared. RESULTS: A significant increase in S-wave velocity was observed in
      cases (rest: 9.4 +/- 3.1; exercise: 13.7 +/- 4.8 cm/s [p < 0.05]). In controls
      there was a statistically significant increase in S-wave velocity (12.9 +/- 2.3
      to 23.0 +/- 7.2 cm/s [p < 0.005]), TAPSE (25.7 +/- 2.4 to 31.0 +/- 3.5 mm [p <
      0.05]) and RVFAC (53.8 +/- 14.7% to 64.4 +/- 9.9% [p < 0.005]). The magnitude of
      change in S-wave velocity (cases: 4.3 +/- 3.3; controls: 10.1 +/- 5.5 cm/s [p <
      0.05]), TAPSE (cases: 0.6 +/- 2.5; controls: 5.3 +/- 3.8 mm [p < 0.05]) and RVFAC
      (cases: -0.4 +/- 11.8; controls: 10.6 +/- 5.9% [p < 0.05]) was significantly
      different between cases and controls. CONCLUSIONS: S-wave velocity, TAPSE and
      RVFAC increased significantly with exercise in controls. S-wave velocity was the
      only parameter that showed a significant increase in cases, although the
      magnitude of this increase was significantly less than in controls.

PMID- 24680556
TI  - Aneurysm of the right sinus of Valsalva dissecting into the interventricular
      septum, submitral aneurysm and left ventricular non-compaction: three rare
      diseases in the same patient.

PMID- 24680557
TI  - Multimarker approach in risk stratification of patients with acute coronary
      syndromes: towards the ideal stratification.

PMID- 24680558
TI  - Dual etiology of dilated cardiomyopathy: the synergistic role of vitamin D
      deficiency.
AB  - Dilated cardiomyopathy is the commonest form of cardiomyopathy in pediatric
      patients. Various causal factors have been identified, including ionic imbalance.
      Calcium ions play an essential role in regulating myocardial contractile
      function, and the harmful role of hypocalcemia as a coadjuvant or even
      precipitating factor of worsening heart failure has been described in rare case
      reports. Multiple causative factors may occasionally be present. We describe the
      first case, to our knowledge, of dilated cardiomyopathy in an infant with severe
      hypocalcemia and viral myocarditis. 

PMID- 24680559
TI  - Clinico-radiological predictors of vascular cognitive impairment (VCI) in
      patients with stroke: a prospective observational study.
AB  - BACKGROUND AND PURPOSE: Cognitive dysfunction occurs commonly following stroke
      and varies in severity. This study was aimed to determine the clinical, neuro
      imaging, laboratory predictors of post stroke cognitive impairment and factors
      related to poor functional outcome in patients with post-stroke vascular
      cognitive impairment (VCI). MATERIAL AND METHODS: We prospectively evaluated 102
      of 240 consecutive stroke patients for 6 months after incident stroke for
      development of VCI. Patients with VCI comprised of those with VCI-no dementia
      (VCIND) and vascular dementia (VaD). Functional outcome was assessed by modified
      Barthel index (MBI). RESULTS: Frequency of post-stroke VCI was 45.1% (46/102):
      26.5% (27/102) having VCI-ND and 18.6% (19/102) having VaD. Patients with VCI
      were more likely to have lower educational and socioeconomic status, diabetes,
      hypertension, prior stroke, multiple risk factors, urinary incontinence, gait
      abnormality, peripheral signs of atherosclerosis, higher blood sugar level on
      admission and LDL levels, strategic site lesion, higher ARWMC (age related white
      matter changes) score, worse stroke severity (NIHSS) and functional outcome
      scores. On logistic regression analysis, lower educational status, strategic site
      lesion, higher ARWMC score and baseline stroke severity score were found to
      independently predict the risk of developing VCI. Worse stroke severity (NIHSS)
      scores and functional status scores at baseline predicted poor outcome in
      patients with VCI. CONCLUSION: Post-stroke cognitive impairment is frequent and
      is associated with poor functional outcome. Predictors like lower educational
      status, strategic site lesion, greater severity of age related white matter
      changes and baseline stroke severity independently contributed to the risk of
      developing VCI in stroke patients.

PMID- 24680560
TI  - Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab.
AB  - IMPORTANCE: Natalizumab was approved in 2004 by the US Food and Drug
      Administration (US-FDA) for treatment of multiple sclerosis (MS), however it was
      temporarily withdrawn after its use was associated with progressive multifocal
      leukoencephalopathy (PML). Other reported adverse events have included melanoma,
      primary central nervous system (CNS) lymphoma, and gastrointestinal
      cryptosporidiosis. An MS exacerbation may occur after discontinuation and immune
      reconstitution inflammatory syndrome (IRIS), particularly in the setting of PML,
      is also possible. We present the first case of cryptococcal meningitis in a
      patient taking natalizumab. Managements of both cryptococcal meningitis and MS
      after discontinuation of natalizumab are the focus of this report. OBSERVATIONS:
      This is a case report describing a 49-year old Caucasian man with relapsing
      remitting MS (RR-MS) on natalizumab. On the twenty-fourth month of natalizumab
      treatment, he developed cryptococcal meningitis, prompting its discontinuation.
      Two months later, off natalizumab, while on antifungal treatment, he developed an
      MS exacerbation. Cerebrospinal fluid (CSF) JC virus polymerase chain reaction
      (PCR) and human immunodeficiency virus (HIV) serology were repeatedly negative.
      CONCLUSIONS AND RELEVANCE: Although specific recommendations for treating
      natalizumab-associated cryptococcal meningitis do not exist, our patient
      discontinued natalizumab and started conventional anti-fungal treatment. Two
      months later, he was treated with steroids due to worsening neurologic status
      from a presumed MS attack. Subsequently, he improved with successful treatment of
      the cryptococcal meningitis, with no new clinical or radiographic exacerbations.

PMID- 24680561
TI  - Dengue-associated hypokalemic paralysis: causal or incidental?
AB  - Dengue-associated hypokalemic paralysis is considered an important but under
      emphasized neuromuscular complication of dengue virus infection. Review of the
      published literature reveals that 35 instances of hypokalemic paralysis
      associated with dengue have been recorded from the Indian subcontinent and all
      but two, were males. The median age of presentation is 29 years and moderate to
      severe grade pure motor quadriparesis is precipitated during the phase of
      defervescence of moderate to high-grade fever. Recovery starts within 12h of
      potassium supplementation and is usually complete in a couple of days.
      Redistribution or increased loss of potassium from the body is speculated as the
      pathophysiological mechanism involved in the causation of hypokalemia. It is not
      possible to derive the exact etiopathological correlation from the published
      literature either due to a lack of comprehensive reporting or inadequate work-up
      of the patients. Curious is the fact that only 35 patients had manifest-paralysis
      when more than two-thirds affected with the dengue virus exhibit hypokalemia;
      whether this indicates a genetically mediated channel disorder or an incidental
      association remains to be seen.

PMID- 24680562
TI  - Neuroprotective effects of JGK-263 in transgenic SOD1-G93A mice of amyotrophic
      lateral sclerosis.
AB  - BACKGROUND: Glycogen synthase kinase-3beta (GSK-3beta) activity plays a central
      role in motor neuron degeneration. GSK-3beta inhibitors have been shown to
      prolong motor neuron survival and suppress disease progression in amyotrophic
      lateral sclerosis (ALS). In this study, we evaluated the therapeutic effects of a
      new GSK-3b inhibitor, JGK-263, on ALS in G93A SOD1 transgenic mice. METHODS:
      Previously, biochemical efficacy of JGK-263 was observed in normal and mutant
      (G93A) hSOD1-transfected motor neuronal cell lines (NSC34). Based on these
      previous results, we administered JGK-263 orally to 93 transgenic mice with the
      human G93A-mutated SOD1 gene. The mice were divided into three groups: a group
      administered 20mg/kg JGK-263, a group administered 50mg/kg JGK-263, and a control
      group not administered with JGK-263. Clinical status, rotarod test, and survival
      rates of transgenic mice with ALS were evaluated. Sixteen mice from each group
      were selected for further biochemical study that involved examination of motor
      neuron count, apoptosis, and cell survival signals. RESULTS: JGK-263
      administration remarkably improved motor function and prolonged the time until
      symptom onset, rotarod failure, and death in transgenic mice with ALS compared to
      control mice. In JGK-263 groups, choline acetyltransferase (ChAT) staining in the
      ventral horn of the lower lumbar spinal cord showed a large number of motor
      neurons, suggesting normal morphology. The neuroprotective effects of JGK-263 in
      ALS mice were also suggested by western blot analysis of spinal cord tissues in
      transgenic mice. CONCLUSION: These results suggest that JGK-263, an oral GSK
      3beta inhibitor, is promising as a novel therapeutic agent for ALS. Still,
      further biochemical studies on the underlying mechanisms and safety of JGK-263
      are necessary.

PMID- 24680563
TI  - Paradoxical reaction in HIV negative tuberculous meningitis.
AB  - This review focusses on paradoxical reactions occurring during the treatment of
      tuberculous meningitis (TBM) in human immunodeficiency virus-negative cases. A
      paradoxical reaction is defined as the worsening of a pre-existing lesion or the
      appearance of new lesion in a patient whose clinical symptoms initially improved
      with anti-tuberculosis treatment. A number of different paradoxical reactions
      have been reported in patients with TBM including expansion of existing cerebral
      tuberculomas, and appearance of new tuberculomas, hydrocephalus, and
      optochiasmatic and spinal arachnoiditis. While the exact mechanism of paradoxical
      reactions is uncertain, an exaggerated immune reaction against Mycobacterium
      tuberculosis-associated antigens is currently the most accepted theory for
      tuberculous paradoxical reaction. Corticosteroids are considered to have a
      beneficial effect in the management of paradoxical reactions. Immuno-modulatory
      drugs, including tumor necrosis factor-alpha antagonists, thalidomide and
      interferon-gamma have been used in isolated cases with more severe forms of
      paradoxical reactions.

PMID- 24680564
TI  - Magnetic resonance imaging reveals Creutzfeldt-Jakob disease in a patient with
      apparent dementia with Lewy bodies.
AB  - The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic
      Creutzfeldt-Jakob disease (CJD) may be challenging. Patients with the original
      diagnosis of possible CJD may occasionally prove to have a pathological diagnosis
      of DLB, while other cases may fulfill the diagnostic clinical criteria for DLB
      but subsequent clinical course, cerebrospinal fluid (CSF) and neuropathology
      findings necessitate diagnostic revision to CJD. We describe a 79-year old
      patient recently diagnosed with dementia with Lewy bodies (DLB) on the basis of
      subacute cognitive decline, visual hallucinations and Parkinsonian features, who
      presented with increasing agitation. Brain neuroimaging with MRI raised the
      diagnostic suspicion of CJD and subsequent diagnostic work-up with
      electroencephalography (EEG) and CSF analysis led to the establishment of CJD
      diagnosis. The present case highlights the clinical utility of novel diagnostic
      CJD criteria that also incorporate neuroimaging findings in the diagnostic CJD
      panel.

PMID- 24680565
TI  - The association of somatic arousal with the symptoms of upper airway resistance
      syndrome.
AB  - OBJECTIVES: We tested the hypothesis that the symptoms of upper airway resistance
      syndrome (UARS) are manifestations of chronic stress. To accomplish this, we
      utilized the score on a self-report questionnaire for somatic arousal (a
      component of stress) to compare somatic arousal between UARS patients and healthy
      controls and, among all participants, to correlate the level of somatic arousal
      with the severity of UARS symptoms. METHODS: We administered the Mood and Anxiety
      Symptom Questionnaire anxious arousal subscale (MASQaas; a 17-item questionnaire
      with increasing levels of arousal scored 17-85) to 12 UARS patients and 12
      healthy controls and compared scores between groups. For all participants, we
      correlated the MASQaas scores with scores for the Epworth Sleepiness Scale (ESS),
      Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale,
      Pittsburgh Sleep Quality Index (PSQI), SF-36 Health Survey, and Perceived
      Deficits Questionnaire (PDQ; assessing cognitive function). RESULTS: Compared to
      healthy controls, UARS patients demonstrated increased somatic arousal (MASQaas
      scores of 18+/-2 and 28+/-7, respectively; p<0.0001). For all participants, the
      MASQaas scores correlated significantly with scores of the ESS (r=0.64;
      p=0.0008), the FACIT-Fatigue scale (r=-0.89; p<0.0001), the PSQI (r=0.70;
      p=0.0002), SF-36 Physical component (r=-0.78; p<0.0001), SF-36 Mental component
      (r=-0.74; p<0.0001), and the PDQ (r=0.89; p<0.0001). CONCLUSIONS: Our findings
      suggest that UARS patients have increased levels of the stress component, somatic
      arousal, proportionate to the severity of their symptoms.

PMID- 24680566
TI  - Takotsubo cardiomyopathy and acute coronary syndrome--overlapping diagnoses will
      lead to confusion.

PMID- 24680567
TI  - Factors influencing readmission after curative gastrectomy for gastric cancer.
AB  - BACKGROUND: The incidence of, and associated risk factors for, readmission after
      potentially curative gastrectomy for patients with gastric cancer has not been
      well studied. We sought to determine the 30-day readmission rate as well as the
      potential risk factors for readmission at our institution in patients undergoing
      gastrectomy for gastric cancer with curative intent. STUDY DESIGN: We performed a
      retrospective analysis of all patients undergoing potentially curative
      gastrectomy for gastric cancer from 1995 to 2011. The 30-day hospital readmission
      rate was determined, and potential clinicopathologic risk factors for readmission
      were examined. RESULTS: Readmission to the hospital within 30 days occurred in
      14.6% (61 of 418) of patients, including 6 patients who were readmitted more than
      once. The most common reasons for readmission included nutritional difficulties
      (n =12, 20%), intra-abdominal fluid collections (n = 11, 18%), and small bowel
      obstruction (n = 6, 10%). Factors associated with a higher 30-day readmission
      rate included type of resection (total gastrectomy, 23% vs subtotal gastrectomy,
      13% vs esophagogastrectomy, 9%, p = 0.016), pre-existing cardiovascular disease
      (17%, p = 0.05), and history of a major postoperative complication (24%, p <
      0.001). Factors not associated with a higher readmission rate included advanced
      age, pre-existing pulmonary disease, T or N stage, extent of lymph node
      dissection, receipt of neoadjuvant chemotherapy or radiotherapy, length of stay
      of the index hospitalization, and destination and level of support on discharge.
      CONCLUSIONS: Readmission after potentially curative gastrectomy for gastric
      cancer is common. Patients with pre-existing cardiovascular disease, those who
      suffer major postoperative complications, and those undergoing total gastric
      resections are at especially high risk for readmission, and strategies designed
      to support these high-risk patients on discharge are warranted.

PMID- 24680568
TI  - Alcohol consumption mitigates apoptosis and mammalian target of rapamycin
      signaling in myocardium.
AB  - BACKGROUND: Epidemiologic studies have shown that individuals who consume low to
      moderate alcohol have a lower risk of cardiovascular disease developing compared
      with abstainers. Although experimental studies confirmed this observation, the
      effect of alcohol on ischemic myocardium is still unclear. We developed a
      clinically relevant animal model of chronic myocardial ischemia to investigate
      the effects of moderate alcohol consumption on the myocardium. STUDY DESIGN:
      Fourteen Yorkshire swine underwent placement of an ameroid constrictor to induce
      chronic myocardial ischemia. Postoperatively, one group was supplemented with 90
      mL 50% EtOH daily (n = 7) and one group was supplemented with 80 g sucrose daily
      to normalize caloric intake between groups (n = 7). After 7 weeks, all animals
      underwent sternotomy, and harvest of the chronically ischemic myocardium and
      nonischemic myocardium. Tissues were analyzed for protein expression and stained
      for apoptosis quantification. RESULTS: In the ischemic myocardium, alcohol down
      regulated the following proapoptotic proteins: tumor necrosis factor-alpha,
      forkhead box protein 03, BCL2-associated death promoter, and cysteine aspartic
      acid-specific protease 9; up-regulated the following prosurvival proteins:
      5'adenosine monophosphate-activated protein kinase, phosphorylated 5'adenosine
      monophosphate-activated protein kinase, and phosphorylated forkhead box protein
      03; and down-regulated mammalian target of rapamycin (MTOR) signaling by down
      regulating MTOR, phosphorylated MTOR, and up-regulating Deptor. In the
      nonischemic myocardium, alcohol up-regulated prosurvival proteins: protein kinase
      B, phosphorylated protein kinase B, phosphorylated B-cell CLL/lymphoma 2,
      5'adenosine monophosphate-activated protein kinase, phosphorylated BCL2
      associated death promoter, phosphorylated forkhead box protein 03, and down
      regulated MTOR signaling by down-regulating phosphorylated MTOR and up-regulating
      Deptor. Alcohol also decreased cell death as measured by terminal
      deoxynucleotidyl transferase mediated dUTP nick-end labeling staining in the
      ischemic and nonischemic myocardium. CONCLUSIONS: Alcohol consumption down
      regulates apoptosis and promotes cell survival in the ischemic and nonischemic
      myocardium. Alcohol also modulates MTOR signaling, which regulates senescence and
      apoptosis. Perhaps MTOR and apoptosis regulation is another mechanism by which
      moderate EtOH consumption is cardioprotective.

PMID- 24680569
TI  - The importance of extreme weight percentile in postoperative morbidity in
      children.
AB  - BACKGROUND: Anthropometric data are important indicators of child health. This
      study sought to determine whether anthropometric data of extreme weight were
      significant predictors of perioperative morbidity in pediatric surgery. STUDY
      DESIGN: This was a cohort study of children 29 days up to 18 years of age
      undergoing surgical procedures at participating American College of Surgeons'
      NSQIP Pediatric hospitals in 2011 and 2012. The primary outcomes were composite
      morbidity and surgical site infection. The primary predictor of interest was
      weight percentile, which was divided into the following categories: <=5(th)
      percentile, 6(th) to 94(th), or >=95(th) percentile. A hierarchical multivariate
      logistic model, adjusting for procedure case mix, demographic, and clinical
      patient characteristic variables, was used to quantify the relationship between
      weight percentile category and outcomes. RESULTS: Children in the <=5th weight
      percentile had 1.19-fold higher odds of overall postoperative morbidity
      developing than children in the nonextreme range (95% CI, 1.10-1.30) when
      controlling for clinical variables. Yet these children did not have higher odds
      of surgical site infection developing. Children in the >=95(th) weight percentile
      did not have a significant increase in overall postoperative morbidity. However,
      they were at 1.35-fold increased odds of surgical site infection compared with
      those in the nonextreme range when controlling for clinical variables (95% CI,
      1.16-1.57). CONCLUSIONS: Both extremely high and extremely low weight percentile
      scores can be associated with increased postoperative complications after
      controlling for clinical variables.

PMID- 24680571
TI  - The general surgery milestones project.

PMID- 24680570
TI  - The migrated liver transplantation candidate: insight into geographic disparities
      in liver distribution.
AB  - BACKGROUND: A minority of liver transplantation (LT) candidates pursue listing at
      multiple centers to achieve transplantation. The purpose of this study was to
      assess the characteristics and outcomes of the migrated LT candidates, that is,
      those who travel to secondary centers seeking LT. STUDY DESIGN: Single-center
      retrospective study from January 1, 2005 to January 1, 2013 at a tertiary care
      center within United Network for Organ Sharing Region 1. Adult recipients who
      were listed at the primary center of interest, but subsequently achieved
      transplantation at a secondary center (Massachusetts General Hospital [MGH]
      migrated; n = 44) were compared with recipients who achieved LT at the primary
      center (MGH-transplanted; n = 279). RESULTS: The MGH-migrated recipients most
      frequently traveled to United Network for Organ Sharing Region 3 (70.5%), with a
      mean (+/-SD) distance traveled of 1,134 (+/-392) miles. The MGH-migrated
      patients, when compared with MGH-transplanted recipients, spent more time on the
      waitlist (907.6 +/- 930.1 days vs 354.9 +/- 533.2 days; p < 0.00001), were more
      likely to have cholestatic liver disease (22.7% vs 6.8%; p = 0.0006) and private
      insurance (80.0% vs 51.6%; p = 0.0005), but were less likely to have alcoholic
      liver disease (2.3% vs 18.6%; p = 0.006) and Model for End-Stage Liver Disease
      exception points (6.8% vs 50.9%; p < 0.00001). On multivariable analysis,
      candidates with private insurance who lacked both alcoholic liver disease and
      Model for End-Stage Liver Disease exception point listing were significantly
      associated with the odds of pursuing migration. Despite achieving LT, MGH
      migrated patients had inferior 5-year patient survival rates (63% vs 80%; p =
      0.03). CONCLUSIONS: A small and distinctive cohort of LT recipients pursue
      migration to achieve transplantation. Travel patterns of migrated LT recipients
      appear to reflect the ongoing geographic disparities in liver distribution and
      underscore the need for alterations in policy to allow for equitable
      distribution.

PMID- 24680572
TI  - Prophylactic mesh vs suture in the closure of the umbilical trocar site after
      laparoscopic cholecystectomy in high-risk patients for incisional hernia. A
      randomized clinical trial.
AB  - BACKGROUND: Prosthetic repair has become the standard method for hernia repair.
      Mesh placement for the prevention of trocar site incisional hernia (TSIH) is
      still a controversial issue. We tested the hypothesis that closure with an
      intraperitoneal prophylactic mesh of the umbilical trocar after a laparoscopic
      cholecystectomy can reduce the incidence of a TSIH in high-risk patients. STUDY
      DESIGN: A randomized clinical trial was conducted among patients undergoing
      elective laparoscopic cholecystectomy who presented the following high-risk
      factors for incisional hernia, according to the literature: age 65 years and
      older, diabetes mellitus, chronic pulmonary disease, and obesity (ie, body mass
      index >=30 kg/m(2)). Patients were assigned to have closure of the umbilical
      trocar site with either nonabsorbable sutures (group A) or intraperitoneal
      polypropylene omega-3 mesh (group B). Trocar site incisional hernia, pain, and
      surgical complications were evaluated at the early postoperative course and at 1,
      6, and 12 months after surgery. RESULTS: A total of 106 patients were randomized
      into the study and 92 patients were finally analyzed, including 47 in group A and
      45 in group B. The TSIH rate was higher in group A (31.9%) than in group B (4.4%)
      (odds ratio = 10.1; 95% CI, 2.15-47.6; p < 0.001)). The wound infection rate was
      4.3%; 8.5% in group A and 0% in group B (odds ratio = 2.04; 95% CI, 1.7-2.5; p =
      0.045). Median postoperative pain evaluated by a visual analogue scale was 3 in
      group A and 2 in group B (p = 0.05). No differences were observed in complication
      rate, operative time, or hospital stay between the groups. CONCLUSIONS:
      Prosthetic closure of the umbilical trocar site after laparoscopic surgery could
      become the standard method for preventing TSIH in high-risk patients.

PMID- 24680573
TI  - Does postoperative drain amylase predict pancreatic fistula after pancreatectomy?
AB  - BACKGROUND: Previous studies suggest that after pancreatectomy, drain fluid
      amylase obtained on postoperative day 1 (DFA1) >5,000 U/L correlates with the
      development of postoperative pancreatic fistula (PF).(1,2) We sought to validate
      whether DFA1 is a clinically useful predictor of PF and to evaluate whether DFA1
      correlates with PF severity. STUDY DESIGN: Using a prospective database, we
      reviewed records from patients having pancreatectomy between 2010 and 2012.
      Presence and grade of PF were determined using the consensus guidelines from the
      International Study Group on Pancreatic Fistula (ISGPF).(1) RESULTS: Sixty-three
      patients who underwent pancreatectomy had a documented DFA1. There were 27 (43%)
      who developed PF: 2 (7%) were grade A, 18 grade B (67%), and 7 were grade C
      (26%). Median DFA1 in patients with PF (4,600 U/L, range 32 to 16,900 U/L) was
      significantly higher than in those without PF (45 U/L, range 2 to 5,840 U/L; p <
      0.001). When DFA1 was analyzed at varying cutoff values, correlation of DFA1 with
      PF was high. Sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) were assessed at varying levels of DFA1. Highest
      sensitivity (96%) and NPV (96%) were obtained with a cutoff DFA1 of <100 U/L. On
      multivariate analysis, DFA1 >100 U/L was the only significant predictor of PF
      when controlling for gland texture, duct size, pathology, and neoadjuvant
      radiation. There was no statistically significant relationship between DFA1 and
      PF grade. CONCLUSIONS: In patients undergoing pancreatic resection, a cutoff DFA1
      of 100 U/L resulted in high sensitivity and NPV. Early drain removal may be safe
      in these patients. Further studies are recommended to validate the role of DFA1
      in excluding PF and assisting in management of surgical drains.

PMID- 24680574
TI  - Laparoscopic vs open right hepatectomy: a value-based analysis.
AB  - BACKGROUND: Current literature lacks sufficient data on outcomes after extensive
      laparoscopic liver resections. We hypothesized that laparoscopic right
      hepatectomy (LRH) is associated with better clinical outcomes and less overall
      hospital costs than open right hepatectomy (ORH), supporting the notion that
      major laparoscopic hepatic resections carry increased value when compared with
      the open approach. STUDY DESIGN: We reviewed medical records of all patients at
      our institution who underwent elective LRH (n = 48) or ORH (n = 57) from May 16,
      2008 to March 1, 2012. Patient demographics, preoperative comorbidities,
      operative details, and postoperative outcomes were compared between the 2 groups.
      Hospital billing data were collected for each case to determine the average
      hospital costs per case. RESULTS: Average operative duration, estimated blood
      loss, intravenous fluid resuscitation requirements, high-grade postoperative
      complications, the need for postoperative admission to the ICU, and hospital
      length of stay were significantly less within the LRH cohort. Thirty-day
      mortality and readmission rates were equivalent between the 2 groups. Despite
      higher operative costs for LRH ($16,605 vs $10,411, p < 0.001), total
      postoperative costs were significantly less ($9,075 for LRH vs $16,341 for ORH, p
      < 0.001), resulting in equivalent overall costs ($25,679 for LRH vs $26,751 for
      ORH, p = 0.65). CONCLUSIONS: Although overall costs between LRH and ORH are
      equivalent, clinical outcomes after LRH are comparable to those after ORH,
      supporting the value of laparoscopy in extensive right hepatic resections.
      Efforts to reduce operative costs of LRH, while maintaining optimal patient
      outcomes, should be the focus of surgeons and hospitals moving forward.

PMID- 24680575
TI  - Impact of a third-year surgical apprenticeship model: perceptions and attitudes
      compared with the traditional medical student clerkship experience.
AB  - BACKGROUND: Current literature suggests that medical students may have negative
      misconceptions of a surgical career partly due to the traditional hierarchical
      structure of the surgical clerkship. We hypothesized that a novel medical student
      apprenticeship would result in positive changes in perceptions of both surgeons
      and surgical careers. STUDY DESIGN: In the 2011 academic year, third-year medical
      students were offered a 2-week apprenticeship elective, in addition to the
      standard 8-week surgical clerkship. Unlike a traditional service, students
      apprenticed directly with participating faculty on a one-on-one basis. At the
      clerkship's end, students received a structured questionnaire assessing
      perceptions and attitudes toward surgeons and a career in surgery. Subjects
      responded anonymously using a 5-point Likert scale. A Wilcoxon Rank-Sum was
      performed comparing students who participated vs those who did not participate in
      the apprenticeship. RESULTS: There was a 99% survey response (105 of 106). Of
      those, 50 (48%) participated in the apprenticeship. Apprenticeship students were
      more likely to view surgeons as content (p < 0.001), well-balanced (p < 0.01),
      respectful (p = 0.01), and as role models (p < 0.005). Apprenticeship students
      were also more likely to participate in the operating room (p < 0.05) and in
      patient management (p < 0.05). There was no difference in an interest to pursue a
      surgical career between groups both before and on completion of the clerkship.
      CONCLUSIONS: Students participating in a surgical apprenticeship had a more
      positive view of surgeons and the field of surgery compared with students not
      participating. An apprenticeship model enhances the surgical clerkship experience
      and improves medical student perceptions of surgery as a career.

PMID- 24680576
TI  - Abnormal vital signs are common after bowel resection and do not predict
      anastomotic leak.
AB  - BACKGROUND: Anastomotic leak is a serious complication of gastrointestinal
      surgery. Abnormal vital signs are often cited in retrospective peer review and
      medicolegal settings as evidence of negligence in the failure to make an early
      diagnosis. We aimed to profile the postoperative courses of patients who undergo
      intestinal anastomosis and determine how reliably abnormal vital signs predict
      anastomotic leaks. STUDY DESIGN: Consecutive patients undergoing bowel resection
      with anastomosis at an academic medical center from July 2009 through July 2011
      were identified from a prospective complication database. The electronic medical
      record was queried for postoperative vital signs and laboratory studies, which
      were digitally abstracted. Abnormal values were defined as temperature >38
      degrees C, white blood cell count <=4,000 or >=12,000 cells/uL, systolic blood
      pressure <=80 mmHg or diastolic blood pressure <=50 mmHg, pulse >=100 beats per
      minute, and respiratory rate >=20 breaths per minute. Patients who developed an
      anastomotic leak were compared with those with an uncomplicated postoperative
      course. RESULTS: Of the 452 patients, 141 (31.2%) suffered a total of 271
      complications, including 19 anastomotic leaks. Even in "uncomplicated"
      recoveries, tachycardia and tachypnea were almost routine, occurring in more than
      half of the patients frequently throughout the postoperative period. Hypotension,
      fever, and leukocytosis were also remarkably common. The positive predictive
      value of any aberrant vital sign or white blood cell count ranged between 4% and
      11%. CONCLUSIONS: Abnormal vital signs are extremely common after bowel resection
      with anastomosis. Even sustained aberrant vital signs and/or leukocytosis are not
      necessarily suggestive of a leak or other postoperative complication.

PMID- 24680578
TI  - Analysis of gene expression changes, caused by exposure to nitrite, in metabolic
      and antioxidant enzymes in the red claw crayfish, Cherax quadricarinatus.
AB  - We evaluated the effect of acute exposure to nitrite on expression of antioxidant
      and metabolic enzyme genes in gill tissue of advanced juvenile Cherax
      quadricarinatus. A 48h nitrite exposure was conducted, using four test
      concentrations (NO2-N=0.5, 1, 1.5 and 2mg L(-1)) plus a control group. The
      relative mRNA expression of mitochondrial manganese superoxide dismutase
      (mMnSOD), cytosolic MnSOD (cMnSOD), extracellular copper/zinc SOD (exCu/ZnSOD),
      catalase (CAT), glutathione S-transferase (GST), arginine kinase (AK), glutamate
      dehydrogenase (GDH), mitochondrial malate dehydrogenase (mMDH), Na(+)/K(+)-ATPase
      alpha-subunit and phosphoenolpyruvate carboxykinase (PEPCK) in gill tissue was
      measured. Significantly increased mRNA expression was observed for all the
      antioxidant enzymes after 12 and 24h. After 48h, they all decreased at high
      nitrite concentrations. The gene expression levels of AK, GDH, mMDH and
      Na(+)/K(+)-ATPase alpha-subunit showed similar trends as the antioxidant enzymes.
      Significant depression of gene expression levels of PEPCK occurred throughout the
      experimental time at high nitrite concentrations. The results indicated that
      nitrite could induce oxidative and metabolic stress in C. quadricarinatus, in a
      time dependent manner, which suggests they could be helpful in predicting
      sublethal nitrite toxicity and useful in environmental monitoring studies.

PMID- 24680577
TI  - Inadequate venous thromboembolism risk stratification predicts venous
      thromboembolic events in surgical intensive care unit patients.
AB  - BACKGROUND: Surgical intensive care unit (SICU) patients are known to be at high
      risk for venous thromboembolism (VTE). The 2005 Caprini Risk Assessment Model
      (RAM) predicts VTE risk in surgical patients. However, a physician's ability to
      accurately complete this RAM and the effect that inaccurate RAM completion might
      have on VTE risk remain unknown. STUDY DESIGN: Between 2009 and 2012, physicians
      completed a 2005 Caprini score for all SICU admissions at our institution. For
      comparison, we used a previously validated, computer-generated score. Regression
      based techniques examined the effect of inadequate risk stratification on
      inpatient VTE risk, when controlling for other confounders. RESULTS: Among 3,338
      consecutive SICU admissions, 55.2% had computer-generated scores that were higher
      than the physician-reported score, and 20.6% of scores were equal. Computer
      generated scores were higher than physician-reported scores for both median (6 vs
      5) and interquartile range (5 to 8 vs 3 to 7). Inter-rater reliability between
      the 2 scores was poor (kappa = 0.238). Risk score underestimation by >=2 points
      was significantly associated with inpatient VTE (7.67% vs 4.59%, p = 0.002).
      Regression analysis demonstrated that each additional day's delay in
      chemoprophylaxis (odds ratio [OR] 1.05, 95% CI 1.01 to 1.08, p = 0.011) and under
      risk stratification by >=2 points (OR 2.46, 95% CI 1.53 to 3.96, p < 0.001) were
      independent predictors of inpatient VTE, as were higher admission APACHE score,
      personal history of VTE, recent pneumonia, and younger age. CONCLUSIONS:
      Physicians under-risk stratify SICU patients when using the 2005 Caprini RAM. As
      hospitals incorporate electronic medical records into daily practice, computer
      calculated Caprini scores may result in more accurate VTE risk stratification.
      Inadequate VTE risk assessment and delay to chemoprophylaxis carry independent
      and significant increased risk for VTE.

PMID- 24680579
TI  - Patient safety and communication: a new assessment for doctors trained in
      countries where language differs from that of the host country: results of a
      pilot using a domain-based assessment.
AB  - OBJECTIVE: Global migration of healthcare workers places responsibility on
      employers to comply with legal employment rights whilst ensuring patient safety
      remains the central goal. We describe the pilot of a communication assessment
      designed for doctors who trained and communicated with patients and colleagues in
      a different language from that of the host country. It is unique in assessing
      clinical communication without assessing knowledge. METHODS: A 14-station OSCE
      was developed using a domain-based marking scheme, covering professional
      communication and English language skills (speaking, listening, reading and
      writing) in routine, acute and emotionally challenging contexts, with patients,
      carers and healthcare teams. Candidates (n=43), non-UK trained volunteers
      applying to the UK Foundation Programme, were provided with relevant station
      information prior to the exam. RESULTS: The criteria for passing the test
      included achieving the pass score and passing 10 or more of the 14 stations. Of
      the 43 candidates, nine failed on the station criteria. Two failed the pass score
      and also the station criteria. The Cronbach's alpha coefficient was 0.866.
      CONCLUSION: This pilot tested 'proof of concept' of a new domain-based
      communication assessment for non-UK trained doctors. PRACTICE IMPLICATIONS: The
      test would enable employers and regulators to verify communication competence and
      safety in clinical contexts, independent of clinical knowledge, for doctors who
      trained in a language different from that of the host country.

PMID- 24680580
TI  - Response to the letter by Vedran Deletis, David B. Mac Donald, Francesco Sala and
      Isabel Fernandez Conejero.

PMID- 24680581
TI  - Under the surface of adolescent psychopathic traits: high-anxious and low-anxious
      subgroups in a community sample of youths.
AB  - In this study, we examined subgroups of adolescents based on their levels of
      psychopathic traits and anxiety. Participants were 914 youths from a community
      sample, with a mean age of 14.28 (SD = .94) years. We used adolescents' self
      reports of psychopathic traits and their parents' reports of the adolescent's
      anxiety to identify distinct subgroups of youths. Using latent class analysis, we
      identified five groups that varied in levels of psychopathic traits and anxiety.
      Two groups were characterized by high levels of psychopathic traits and high or
      low scores on anxiety. Validation of these subgroups revealed that they differed
      significantly from each other in theoretically meaningful ways-the low-anxious
      subgroup reported higher levels of psychopathic traits, lower levels of
      impulsivity and hyperactivity, and lower levels of aggression than the high
      anxious group. These findings are in line with previous empirical research and
      provide support that anxiety discriminates between two subgroups of adolescents
      with psychopathic traits.

PMID- 24680582
TI  - Recommendations for scale-up of community-based misoprostol distribution
      programs.
AB  - Community-based distribution of misoprostol for prevention of postpartum
      hemorrhage (PPH) in resource-poor settings has been shown to be safe and
      effective. However, global recommendations for prenatal distribution and
      monitoring within a community setting are not yet available. In order to
      successfully translate misoprostol and PPH research into policy and practice,
      several critical points must be considered. A focus on engaging the community,
      emphasizing the safe nature of community-based misoprostol distribution, supply
      chain management, effective distribution, coverage, and monitoring plans are
      essential elements to community-based misoprostol program introduction,
      expansion, or scale-up. 

PMID- 24680583
TI  - Obesity crisis in cancer care: gynecologic cancer prevention, treatment, and
      survivorship in obese women in the United States.

PMID- 24680584
TI  - Body mass index, physical activity, and mortality in women diagnosed with ovarian
      cancer: results from the Women's Health Initiative.
AB  - BACKGROUND: Ovarian cancer is often diagnosed at late stages and consequently the
      5-year survival rate is only 44%. However, there is limited knowledge of the
      association of modifiable lifestyle factors, such as physical activity and
      obesity on mortality among women diagnosed with ovarian cancer. The purpose of
      our study was to prospectively investigate the association of (1) measured body
      mass index (BMI), and (2) self-reported physical activity with ovarian cancer
      specific and all-cause mortality in postmenopausal women enrolled in the Women's
      Health Initiative (WHI). METHODS: Participants were 600 women diagnosed with
      primary ovarian cancer subsequent to enrollment in WHI. Exposure data, including
      measured height and weight and reported physical activity from recreation and
      walking, used in this analysis were ascertained at the baseline visit for the
      WHI. Cox proportional hazard regression was used to examine the associations
      between BMI, physical activity and mortality endpoints. RESULTS: Vigorous
      intensity physical activity was associated with a 26% lower risk of ovarian
      cancer specific-mortality (HR=0.74; 95% CI: 0.56-0.98) and a 24% lower risk of
      all-cause mortality (HR=0.76; 95% CI: 0.58-0.98) compared to no vigorous
      intensity physical activity. BMI was not associated with mortality. CONCLUSIONS:
      Participating in vigorous-intensity physical activity, assessed prior to ovarian
      cancer diagnosis, appears to be associated with a lower risk of ovarian cancer
      mortality.

PMID- 24680585
TI  - Measurements of adiposity as clinical biomarkers for first-line bevacizumab-based
      chemotherapy in epithelial ovarian cancer.
AB  - OBJECTIVE: There is a lack of reliable indicators to predict who will benefit
      most from anti-angiogenic therapy, such as bevacizumab. Recognizing obesity is
      associated with increased levels of VEGF, the main target of bevacizumab, we
      sought to assess if adiposity, measured in terms of BMI, subcutaneous fat area
      (SFA), and visceral fat area (VFA) was prognostic. METHODS: Reviewed 46 patients
      with advanced EOC who received primary treatment with bevacizumab-based
      chemotherapy (N=21) or chemotherapy alone (N=25) for whom complete records, CT
      prior to the first cycle of chemo, and serum were available. CT was used to
      measure SFA and VFA by radiologists blinded to outcomes. ELISA was used to
      measure serum levels of VEGF and angiopoietin-2 in the bevacizumab group.
      RESULTS: BMI, SFA, and VFA were dichotomized using the median and categorized as
      "high" or "low". In the bevacizumab group median PFS was shorter for patients
      with high BMI (9.8 vs. 24.7months, p=0.03), while in the chemotherapy group
      median PFS was similar between high and low BMI (17.6 vs. 11.9months, p=0.19). In
      the bevacizumab group patients with a high BMI had higher median levels of VEGF
      and angiopoietin-2, 371.9 vs. 191.4pg/ml (p=0.05) and 45.9 vs. 16.6pg/ml (p=0.09)
      respectively. On multivariate analysis neither BMI, SFA, nor VFA were associated
      with PFS (p=0.13, p=0.86, p=0.16 respectively) or OS (p=0.14, p=0.93, p=0.28
      respectively) in the chemotherapy group. However, in the bevacizumab group BMI
      was significantly associated with PFS (p=0.02); accounting for confounders
      adjusted HR for high vs. low BMI was 5.16 (95% CI 1.31-20.24). Additionally in
      the bevacizumab group SFA was significantly associated with OS (p=0.03);
      accounting for confounders adjusted HR for high vs. low SFA was 3.58 (95% CI 1.12
      11.43). CONCLUSION: Results provide the first evidence in EOC that patients with
      high levels of adiposity may not derive benefit from bevacizumab and that
      measurements of adiposity are likely to be a useful biomarker.

PMID- 24680586
TI  - Impact of obesity on chemotherapy dosing for women with advanced stage serous
      ovarian cancer in the Australian Ovarian Cancer Study (AOCS).
AB  - OBJECTIVES: Obesity is an increasing health problem that is reported to influence
      chemotherapy dosing. The extent to which this occurs and whether this affects
      outcomes in ovarian cancer was unclear. To describe chemotherapy dosing practices
      in normal, overweight and obese patients treated for FIGO Stage III/IV serous
      ovarian cancer in the Australian Ovarian Cancer Study (AOCS). To evaluate the
      relationship between body mass index (BMI), dose intensity of chemotherapy
      received, overall survival (OS) and progression free survival (PFS). METHODS:
      Patient characteristics including age, height, weight, FIGO stage, serum
      creatinine, primary chemotherapy received and outcome data were extracted from
      medical records and entered into the AOCS database. Outcomes were analysed
      against BMI and relative dose intensity (RDI) received, based on calculations
      derived from a standard regimen (carboplatin AUC 5 and paclitaxel 175mg/m(2)).
      RESULTS: 333 women were included in the analysis. 27% were overweight and 21%
      were obese. In cycle 1 66% of obese patients received carboplatin doses more than
      5% below their optimal calculated dose, and 32% received sub-optimal paclitaxel
      doses, compared to 25% and 13% of normal weight patients respectively. Obese
      women were more likely to have received <85% RDI for carboplatin compared to
      normal weight women (p<0.001). BMI group and RDI of carboplatin and paclitaxel
      were not predictors of OS. Women who received less than 85% RDI for carboplatin
      had a worse PFS (univariate analysis, median PFS 11 versus 15 months; p=0.04).
      There was no significant association between RDI and OS or PFS in multivariate
      analysis. CONCLUSIONS: Obesity is common in ovarian cancer patients, and commonly
      results in lower chemotherapy dosing than recommended. Analysis of chemotherapy
      dosing from this study suggests that reduced dose intensity of carboplatin, which
      was more common in obese women, may impact on PFS in patients with advanced
      serous ovarian cancer.

PMID- 24680587
TI  - The impact of obesity on surgical staging, complications, and survival with
      uterine cancer: a Gynecologic Oncology Group LAP2 ancillary data study.
AB  - OBJECTIVE: To determine the association of body mass index (BMI) on
      complications, recurrence, and survival in GOG LAP2, a randomized comparison of
      laparoscopic versus open staging in clinically early stage uterine cancer (EC).
      METHODS: An ancillary data analysis of GOG LAP2 was performed. Categorical
      variables were compared using Pearson chi-square test and continuous variables
      using the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests by BMI group. Survival
      was estimated using the Kaplan-Meier method. Cox proportional hazards model was
      used to evaluate independent prognostic factors on survival. Statistical tests
      were two-tailed with alpha=0.05, except where noted. Statistical analyses
      utilized R programming language. RESULTS: 2596 women were included. BMI (kg/m(2))
      groups were <25 (29.5%), 25-30 (28.2%), 30-35 (21%), 35-40 (10.9%), and >=40
      (10.4%). Stage (p=0.021), grade (p<0.001), and histology (p=0.005) differed by
      BMI. Obese women were less likely to have high risk (HR) disease (+lymph
      nodes/ovaries/cytology) or tumor features that met GOG99 high intermediate risk
      (HIR) criteria (p<0.001). Adjuvant therapy (p=0.151) and recurrence (p=0.46) did
      not vary by BMI. Hospitalization >2days, antibiotic use, wound infection, and
      venous thrombophlebitis were higher with BMI >=40. BMI (p=0.016), age (p<0.0001),
      race (p=0.033), and risk group (p<0.0001) predicted all-cause mortality. BMI was
      not predictive of disease-specific survival (p=0.79), but age (p=0.032) and risk
      group (p<0.0001) were significant factors. CONCLUSION: Obese women have greater
      surgical risk and lower risk of metastatic disease. BMI is associated with all
      cause but not disease-specific mortality, emphasizing the detrimental effect of
      obesity (independent of EC), which deserves particular attention.

PMID- 24680588
TI  - The complex triad of obesity, diabetes and race in Type I and II endometrial
      cancers: prevalence and prognostic significance.
AB  - BACKGROUND: We examined the distribution of obesity, diabetes, and race in Type I
      and Type II endometrial cancers (EC) and their associations with clinical
      outcomes. METHODS: A multi-institutional retrospective analysis of Type I and II
      EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid),
      Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and
      high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared.
      Univariate and multivariate analyses were used to determine time-to-recurrence
      (TTR), recurrence-free survival (RFS), and overall survival (OS). RESULTS: Type I
      EC patients were more frequently obese than Type II (66% versus 51%, p<0.0001)
      and had similar rates of diabetes (25% versus 23%, p=0.69). African-Americans
      (AA) had higher median BMI than Caucasians in both Type I (p<0.001) and II
      (p<0.001) ECs, and were twice as likely to have diabetes (p<0.001). In Type I EC,
      DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR
      1.38, 95%CI 1.01-1.89; OS HR 1.86, 95%CI 1.30-2.67), but not with TTR. BMI was
      associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98,
      95%CI 0.95-1.0), but not with RFS or OS. There was no association between DM or
      BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS
      on adjusted analyses in any group. CONCLUSIONS: Obesity and diabetes are highly
      prevalent in Type I and II ECs, especially in AA. DM was associated with worse
      RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type
      II or HG EC.

PMID- 24680589
TI  - Impact of obesity on the results of fertility-sparing management for atypical
      hyperplasia and grade 1 endometrial cancer.
AB  - OBJECTIVES: The aim of the present study was to evaluate the impact of obesity on
      reproductive and oncologic outcomes on the success of fertility-sparing
      management. METHODS: This retrospective multicenter cohort study included women
      treated conservatively for atypical hyperplasia (AH) and endometrial cancer (EC)
      to preserve fertility. Five inclusion criteria were defined: (i) the presence of
      AH or grade 1 EC confirmed by two pathologists; (ii) adequate radiological
      examination before conservative management; (iii) available body mass index (BMI)
      at the beginning of treatment; and (iv) a minimum follow-up time of six months.
      RESULTS: Forty patients fulfilled the inclusion criteria (17 had EC, and 23 had
      AH), mean age and BMI were 33 years and 29kg/m(2) respectively. Among the 15
      obese patients, after medical treatment, 10 patients responded (67%) and three
      relapsed, whereas in the 25 non-obese patients, 19 responded (76%) and three
      relapsed (p=0.72). The overall pregnancy rate and follow-up time were 35% and 35
      months respectively. Among the 15 obese patients, after medical treatment, two
      patients became pregnant, whereas in the 25 non-obese patients, 12 became
      pregnant (p=0.04). CONCLUSION: Despite similar response and recurrence rates, our
      results suggest that fertility-sparing management for AH and EC is associated
      with a lower probability of pregnancy in obese patients.

PMID- 24680590
TI  - Endometrial cancer in morbidly obese women: do racial disparities affect surgical
      or survival outcomes?
AB  - OBJECTIVE: Endometrial cancer mortality disproportionately affects black women
      and whether greater prevalence of obesity plays a role in this disparity is
      unknown. We examine the effect of race on post-surgical complications, length of
      stay, and mortality specifically in a morbidly obese population. METHODS: Black
      and white women with endometrial cancer diagnosed from 1996 to 2012 were
      identified from the University Pathology Group database in Detroit, Michigan, and
      records were retrospectively reviewed to obtain clinicopathological, demographic,
      and surgical information. Analysis was limited to those with a body mass index of
      40kg/m(2) or greater. Differences in the distribution of variables by race were
      assessed by chi-squared tests and t-tests. Kaplan-Meier and Cox regression
      analyses were performed to examine factors associated with mortality. RESULTS: 97
      white and 89 black morbidly obese women were included in this analysis. Black
      women were more likely to have type II tumors (33.7% versus 15.5% of white women,
      p-value=0.003). Hypertension was more prevalent in black women (76.4% versus
      58.8%, p-value=0.009), and they had longer hospital stays after surgery despite
      similar rates of open vs minimally invasive procedures and lymph node dissection
      (mean days=5.4) compared to whites (mean days=3.5, p-value=0.036). Wound
      infection was the most common complication (16.5% in whites and 14.4% in blacks,
      p-value=0.888). Blacks were more likely to suffer other complications, but
      overall the proportions did not differ by race. In univariate analyses, black
      women had higher risk of endometrial cancer-related death (p-value=0.090). No
      racial differences were noted in adjusted survival analyses. CONCLUSION: A more
      complete investigation, incorporating socio-demographic factors, is warranted to
      understand the effects of morbid obesity and race on endometrial cancer.

PMID- 24680592
TI  - Endometrial polyps in obese asymptomatic pre and postmenopausal patients with
      breast cancer: is screening necessary?
AB  - OBJECTIVE: To evaluate the prevalence of endometrial polyps in obese asymptomatic
      pre and postmenopausal patients with breast cancer and to know if a baseline
      pretamoxifen endometrial assessment should be taken into consideration in these
      women at high risk. METHODS: A cross-sectional study was carried out with 201
      women with breast cancer. A diagnostic hysteroscopy was performed in all women.
      All formations suspected as polyps were removed. The prevalence of endometrial
      polyps was analyzed in all patients (n=182) and in premenopausal (n=49) and
      postmenopausal (n=118) women with estrogen receptor (ER) positive breast cancer
      (BC) according to their body mass index (BMI) and other risk factors. RESULTS:
      Hysteroscopic evaluation was possible in 182 cases (90.5%). Of the total of
      women, 160 (87.9%) were ER(+)BC patients, 133 (73.1%) postmenopausal women and
      41.5% were obese (BMI>=30kg/m(2)). Endometrial polyps were found in 52 cases
      (28.5%) (3 cases of simple hyperplasia harbored within a polyp). In premenopausal
      patients with ER(+)BC, there were no statistical differences in endometrial
      polyps according to their BMI (22.3% in non-obese women vs 31.7% in obese) while
      in all patients (26.4% in non-obese vs 44.0% in obese) and in postmenopausal
      women with ER(+)BC (25.9% in non-obese vs 48.6% in obese) there were statistical
      differences. In all women the relative risk (RR) of endometrial polyps in obese
      patients was 2.24 (1.01-4.83), in obese postmenopausal women with ER(+)BC was
      2.75 (1.01-7.40) and in obese premenopausal patients with ER(+)BC was 1.42 (0.80
      3.29). CONCLUSIONS: Asymptomatic women with breast cancer have a high prevalence
      of baseline subclinical endometrial polyps and it is very high in obese
      postmenopausal patients with estrogen receptor positive breast cancer. Therefore,
      there may be a future role for baseline pretamoxifen screening of some sort for
      the obese asymptomatic postmenopausal patient, especially if they are elderly and
      ER positive.

PMID- 24680591
TI  - Response to an exercise intervention after endometrial cancer: differences
      between obese and non-obese survivors.
AB  - OBJECTIVE: The objective of this paper is to describe baseline differences
      between obese and non-obese endometrial cancer survivor in anthropometrics,
      exercise behavior, fitness, heart rate and blood pressure, and quality of life,
      and to analyze whether the effect of a home-based exercise intervention on these
      outcomes differed for obese and non-obese participants. METHODS: One hundred post
      treatment Stage I-IIIa endometrial cancer survivors participated in a single arm
      6month study in which they received a home-based exercise intervention.
      Cardiorespiratory fitness, anthropometrics, and exercise behavior were measured
      every two months, and quality of life (QOL) and psychological distress were
      measured at baseline and 6months. RESULTS: Adjusting for potential confounders,
      at baseline obese survivors had poorer cardiorespiratory fitness (p=.002), higher
      systolic blood pressure (p=.018), and lower physical functioning (p<.001) and
      ratings of general health (p=.002), and more pain (p=.037) and somatization
      (.002). Significant improvements were seen in exercise behavior, resting heart
      rate, systolic blood pressure, and multiple QOL domains over the course of the
      intervention. Obese survivors had less improvement in exercise behavior and
      cardiorespiratory fitness than non-obese survivors, but there were no differences
      with regard to improvements in QOL and stress. CONCLUSIONS: Home based exercise
      interventions are beneficial to endometrial cancer survivors, including those
      whose BMI is in the obese range. While obese survivors have lower levels of
      physical activity and fitness, they experienced similar activity, fitness,
      quality of life and mental health benefits. Exercise should be encouraged in
      endometrial cancer survivors, including those who are obese.

PMID- 24680593
TI  - Bariatric surgery decreases the risk of uterine malignancy.
AB  - OBJECTIVE: To describe the risk of uterine malignancy among women who have had
      weight loss surgery. METHODS: We performed a retrospective cohort study among
      inpatient admissions of women 18years, or older, registered in the University
      HealthSystem Consortium (UHC) dataset. The rate of uterine malignancy per
      hospital admission was calculated. Rates were compared according to whether
      diagnoses at the time of discharge included history of bariatric surgery, and
      further, according to whether there was a diagnosis of obesity. RESULTS: In
      admissions of patients who did not have a history of prior bariatric surgery, the
      rate of uterine malignancy was 599/100,000 (95% CI 590 to 610). Among obese women
      who had not previously undergone bariatric operations, the rate was 1409/100,000
      (95% CI 1380 to 1440). Of women admitted who had a history of bariatric surgery,
      the rate of uterine malignancy was 408/100,000 (95% CI 370 to 450). The relative
      risk of uterine malignancy in all admissions for women who had prior bariatric
      surgery, compared to obese women who had not had bariatric surgery, was 0.29 (95%
      CI 0.26-0.32). Among women who had bariatric surgery and were not currently
      obese, the relative risk of uterine malignancy was 0.19 (95% CI 0.17-0.22)
      compared to obese women who had not undergone bariatric surgery. CONCLUSION: A
      history of bariatric surgery is associated with a 71% reduced risk for uterine
      malignancy overall, and an 81% reduced risk if normal weight is maintained after
      surgery. This finding suggests that obesity may be a modifiable risk factor
      related to development of endometrial cancer.

PMID- 24680594
TI  - Perceptions of obesity and cancer risk in female bariatric surgery candidates:
      highlighting the need for physician action for unsuspectingly obese and high risk
      patients.
AB  - OBJECTIVES: To determine: 1) whether obese women perceive themselves to be obese
      or at risk for malignancy, 2) perceived impact of obesity on cancer risks, 3)
      compliance with cancer screening, and 4) rates of menstrual dysfunction. METHODS:
      Surveys were administered to female patients presenting for bariatric weight loss
      surgery. Demographics, gynecologic history, perception of cancer risk, and
      screening history were collected/analyzed. Women were categorized as obese (BMI:
      30-39kg/m(2)), morbidly obese (40-49kg/m(2)), super obese (>=50kg/m(2)) and
      compared. RESULTS: Ninety-three women (mean age: 44.9 years, mean BMI:
      48.7kg/m(2)) participated and 45.7% felt they were in 'good', 'very good', or
      'excellent' health despite frequent medical comorbidities. As BMI increased,
      women were more likely to correctly identify themselves as obese (23% of obese
      vs. 77% of morbidly obese vs. 85% of super obese; p<0.001) but there were no
      significant differences in comorbidities. Two-thirds of women correctly
      identified obesity as a risk factor for uterine cancer, yet 48% of those
      retaining a uterus perceived that it was "not likely/not possible" to develop
      uterine cancer. Menstrual irregularities were common as was evaluation and
      interventions for the same; 32% had prior hysterectomy. Participation in cancer
      screening was robust. CONCLUSIONS: Women presenting for bariatric surgery have
      high rates of menstrual dysfunction. While they perceive that obesity increases
      uterine cancer risk, they often do not perceive themselves to be at risk. This
      disconnect may stem from the fact that many failed to identify themselves as
      obese perhaps because overweight/obesity has become the norm in U.S. society.

PMID- 24680595
TI  - Hormone receptor expression patterns in the endometrium of asymptomatic morbidly
      obese women before and after bariatric surgery.
AB  - OBJECTIVE: Obesity increases risk for endometrial neoplasia, but neither the
      pathophysiology nor the effects of weight loss on the risk are well established.
      We attempted to characterize the molecular profile of the endometrium of
      asymptomatic women with morbid obesity before and following bariatric surgery
      induced weight loss. METHODS: 59 asymptomatic, morbidly obese women underwent
      endometrial sampling before bariatric surgery; 46 (78%) of these returned one
      year later for re-biopsy (median weight loss of 41kg). Duplicate samples from
      these specimens were scored for expression of estrogen receptor (ER),
      progesterone receptor (PR), androgen receptor (AR), and Ki-67 by two independent,
      blinded pathologists using an H-score [staining intensity (0-3)*(percent of
      tissue involved)]. RESULTS: The prevalence of hyperplasia pre-operatively was 7%
      overall and 10% among patients not on an anti-estrogen. ER H-scores were similar
      before and after surgery overall (median 190 and 196 respectively, p=0.82), but
      patients with hyperplasia had higher pre-operative H-scores (median 256, p<0.001)
      and experienced greater H-score drops, than those without hyperplasia (-112 vs
      +50, p=0.028). In two patients with persistent hyperplasia at one year, ER H
      scores fell to levels that were similar to those without pathology. One patient
      who developed hyperplasia during the study period had a rising ER H-score.
      Patients with hyperplasia had higher median PR H-scores pre-operatively (284 vs
      188, p=0.01), which normalized through greater drops (75 vs 0, p=0.053). AR H
      scores dropped significantly after surgery (13 vs 2, p=0.015), but were similar
      between patients with and without hyperplasia (p=0.33). Weight loss did not
      affect Ki-67 proliferation index. CONCLUSION: Asymptomatic morbidly obese
      patients have a high prevalence of occult hyperplasia, characterized by
      relatively high hormone receptor expression. These profiles appear to normalize
      with weight loss and in advance of pathologically identifiable changes. These
      data suggest a potential role for screening this population as well as the
      possibility that weight loss may be a valid treatment strategy for risk
      reduction.

PMID- 24680596
TI  - CGRRF1 as a novel biomarker of tissue response to metformin in the context of
      obesity.
AB  - OBJECTIVE: Obesity-associated hyperestrogenism and hyperinsulinemia contribute
      significantly to the pathogenesis of endometrial cancer. We recently demonstrated
      that metformin, a drug long used for treatment of type 2 diabetes, attenuates
      both insulin- and estrogen-mediated proliferative signaling in the obese rat
      endometrium. In this study, we sought to identify tissue biomarkers that may
      prove clinically useful to predict tissue response for both prevention and
      therapeutic studies. We identified CGRRF1 (cell growth regulator with ring finger
      domain 1) as a novel metformin-responsive gene and characterized its possible
      role in endometrial cancer prevention. METHODS: CGRRF1 mRNA expression was
      evaluated by RT-qPCR in the endometrium of obese and lean rats, and also in
      normal and malignant human endometrium. CGRRF1 levels were genetically
      manipulated in endometrial cancer cells, and its effects on proliferation and
      apoptosis were evaluated by MTT and Western blot. RESULTS: CGRRF1 is
      significantly induced by metformin treatment in the obese rat endometrium. In
      vitro studies demonstrate that overexpression of CGRRF1 inhibits endometrial
      cancer cell proliferation. Analysis of human endometrial tumors reveals that
      CGRRF1 expression is significantly lower in hyperplasia, Grade 1, Grade 2, Grade
      3, MMMT, and UPSC endometrial tumors compared to normal human endometrium
      (p<0.05), suggesting that loss of CGRRF1 is associated with the presence of
      disease. CONCLUSION: CGRRF1 represents a novel, reproducible tissue marker of
      metformin response in the obese endometrium. Furthermore, our preliminary data
      suggests that up-regulation of CGRRF1 expression may prove clinically useful in
      the prevention or treatment of endometrial cancer.

PMID- 24680597
TI  - Obesity increases tumor aggressiveness in a genetically engineered mouse model of
      serous ovarian cancer.
AB  - OBJECTIVES: Obesity is associated with increased risk and worse outcomes for
      ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer
      progression in a genetically engineered mouse model of serous ovarian cancer.
      METHODS: We utilized a unique serous ovarian cancer mouse model that specifically
      deletes the tumor suppressor genes, Brca1 and p53, and inactivates the
      retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via
      injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa
      cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60%
      calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat
      in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6
      months after AdCre injection and evaluated histologically. Untargeted metabolomic
      and gene expression profiling was performed to assess differences in the ovarian
      tumors from obese versus non-obese KpB mice. RESULTS: At sacrifice, mice on the
      HFD (obese) were twice the weight of mice on the LFD (non-obese) (51g versus 31g,
      p=0.0003). Ovarian tumors were significantly larger in the obese versus non-obese
      mice (3.7cm(2) versus 1.2cm(2), p=0.0065). Gene expression and metabolomic
      profiling indicated statistically significant differences between the ovarian
      tumors from the obese versus non-obese mice, including metabolically relevant
      pathways.

PMID- 24680598
TI  - The varied contribution of significant others to Complementary and Alternative
      Medicine (CAM) uptake by men with cancer: a qualitative analysis.
AB  - PURPOSE: To explore how men's Significant Others (SOs), including family members
      and close friends, contribute to the uptake and maintenance of specific CAM
      therapies. METHODS: This study was the second, qualitative phase of a mixed
      methods project investigating the use of CAM in an Australian male cancer
      population. Male participants were purposefully selected from a pool of 403
      patients who answered a survey in the first quantitative phase (94% response rate
      and 86% consent rate for follow-up interview). Then semi-structured interviews
      among 26 men with a variety of cancers and 24 SOs were conducted. All 43
      interviews were recorded, transcribed, and analysed thematically. RESULTS: Men
      used CAM/Natural products to cope with physical concerns, and this was actively
      supported by men's SOs who contributed to the uptake and maintenance of these
      CAMs. The shared CAM preparation and consumption functioned to strengthen the
      bond between men and their SOs, and also helped men's SOs to cope with
      uncertainty and regain control. In contrast, men practiced CAM/Mind-body medicine
      to receive emotional benefits, and only rarely shared this practice with their
      SOs, indicating a need for coping with emotions in a private way. CONCLUSIONS:
      Men's CAM use is a multifaceted process that can be better understood by
      considering CAM categories separately. CAM/Natural products help men to cope with
      physical concerns, while CAM/Mind-body medicine assist men to cope with their
      emotions in a private way. Oncology professionals can use this information to
      better promote and implement integrative cancer care services.

PMID- 24680599
TI  - Apropos "Congenital rubella syndrome and immunity status of immigrant women
      living in southern Italy: a cross-sectional, seroepidemiological investigation".

PMID- 24680600
TI  - Childhood vaccination associated adverse events by sex: a literature review.
AB  - BACKGROUND: Most approved medicines, including vaccines can be associated with
      adverse events. A vaccine adverse event is defined as any untoward medical
      occurrence which follows vaccination, but which does not necessarily have a
      causal relationship with the administration of the vaccine. METHODS: The
      objective of this structured literature review is to analyse the adverse events
      reported with vaccinations usually done during childhood and adolescence: human
      papilloma virus vaccine, hepatitis B vaccine and measles-mumps-rubella vaccine.
      We evaluated the vaccine literature on children and adolescents by sex. We
      searched the Cochrane Database, Medline (Pubmed) and Embase using predefined
      terms. RESULTS: Of the 417 publications retrieved from searches in the 3
      databases, 89 papers (21%) were identified as potentially relevant to the review.
      On further scrutiny 41 of these satisfied the criteria for inclusion in the
      analysis. Serious adverse events related to vaccinations were rare. We found some
      possible sex related vaccine adverse events. Few trials however reported adverse
      events by age and sex and very few analyses evaluated the observed differences.
      CONCLUSIONS: Despite earlier calls for sex-specific analyses of clinical studies,
      we found that vaccine trials were rarely reported and published by sex.
      Prospectively collated vaccine safety data in children and adolescents should be
      analysed by age and sex, so that clinical trial results can form an evidence base
      for vaccine practice recommendations.

PMID- 24680601
TI  - Glucagon-like peptide-1 production in the GLUTag cell line is impaired by free
      fatty acids via endoplasmic reticulum stress.
AB  - OBJECTS: Glucagon-like peptide-1 (GLP-1) is secreted from intestinal L cells,
      enhances glucose-stimulated insulin secretion, and protects pancreas beta cells.
      However, few studies have examined hypernutrition stress in L cells and its
      effects on their function. Here, we demonstrated that a high-fat diet reduced
      glucose-stimulated secretion of GLP-1 and induced expression of an endoplasmic
      reticulum (ER) stress markers in the intestine of a diet-induced obesity mouse
      model. METHODS: To clarify whether ER stress in L cells caused the attenuation of
      GLP-1 secretion, we treated the mouse intestinal L cell line, GLUTag cells with
      palmitate or oleate. RESULTS: Palmitate, but not oleate caused ER stress and
      decreased the protein levels of prohormone convertase 1/3 (PC1/3), an essential
      enzyme in GLP-1 production. The same phenomena were observed in GLUTag cells
      treated with in ER stress inducer, thapsigargin. Moreover, oleate improved
      palmitate-induced ER stress, reduced protein and activity levels of PC1/3, and
      attenuated GLP-1 secretion from GLUTag cells. CONCLUSIONS/INTERPRETATION: These
      results suggest that the intake of abundant saturated fatty acids induces ER
      stress in the intestine and decreases GLP-1 production.

PMID- 24680602
TI  - The immuno-pathological conversions of canine demodicosis.
AB  - Canine demodicosis is a common but exigent noncontagious parasitic dermatosis
      caused by overpopulation of the host-specific follicular mites of various Demodex
      species. Receptivity of dogs to demodicosis and progression of the clinical
      disease are influenced by numerous factors including; genetic defect, alteration
      of skin's structure and biochemistry, immunological disorders, hormonal status,
      breed, age, nutritional status, oxidative stress, length of hair coat, stage of
      oestrus cycle, parturition, endoparasitism and debilitating diseases. Of these,
      the immune status is thought to be the most significant. Thus, in the present
      review we intended to edify the immuno-pathological conversions of canine
      demodicosis. Generalized demodicosis requires a cutaneous environment that is
      ecologically and immunologically favorable for extreme colonization of demodectic
      mites. Demodex canis mites can down regulate the CD4+ T cells; possibly by an
      increased rate of apoptosis or immunological exhaustion of CD4+ T cells. An
      increased apoptosis of peripheral leukocytes confers progression of the clinical
      manifestations. Mites induced elevation of TGF-beta and inhibition of TNF-alpha
      mRNA expression might be a key factor for revealing the difference in the
      mechanism of onset between localized and generalized demodicosis. Moreover, an
      elevated serum level of IL-10 could be accountable for the recurrence as well as
      occurrence of demodicosis in dogs. Over production of reactive oxygen species can
      corroborate immunological discrepancies in dogs with demodicosis. 

PMID- 24680603
TI  - A study of the level and dynamics of Eimeria populations in naturally infected,
      grazing beef cattle at various stages of production in the Mid-Atlantic USA.
AB  - There is little information available on the species dynamics of eimerian
      parasites in grazing cattle in the central Appalachian region of the United
      States. Therefore, the objective of this study was to describe the level of
      infection and species dynamics of Eimeria spp. in grazing beef cattle of various
      age groups over the course of a year in the central Appalachian region. Rectal
      fecal samples were collected from male and female calves (n=72) monthly from May
      through October 2005, heifers only (n=36) monthly from November 2005 to April
      2006, and cows (n=72) in May, July, and September, 2005. Eimeria spp. oocysts
      were seen in 399 of 414 (96%) fecal samples collected from the calves from May
      through October. Fecal oocysts counts (FOC) in the calves were lower (P<0.05) in
      May than all other months and no significant differences were detected from June
      through September. Eimeria spp. oocysts were detected in 198 of 213 (92%) of
      fecal samples collected from the 36 replacement heifers monthly from November to
      April and monthly mean FOC did not differ during this time period. The prevalence
      of oocyst shedding increased to 100% in calves in September and remained near
      100% in the replacement heifers during the sampling period. Eimeria spp. oocysts
      were also detected in 150 of 200 (75%) samples collected in May, July, and
      September from the cows and mean FOC did not differ significantly over the
      sampling period. Eimeria spp. composition was dominated by Eimeria bovis in fecal
      samples collected from calves, replacement heifers and cows. Mixed Eimeria spp.
      infections were, however, common in all groups and 13 Eimeria spp. oocysts were
      identified throughout the sampling period.

PMID- 24680604
TI  - Sarcocystis neurona schizonts-associated encephalitis, chorioretinitis, and
      myositis in a two-month-old dog simulating toxoplasmosis, and presence of mature
      sarcocysts in muscles.
AB  - Sarcocystis neurona is an unusual species of the genus Sarcocystis. Opossums
      (Didelphis virginianus, D. albiventris) are the definitive hosts and several
      other species, including dogs, cats, marine mammals, and horses are intermediate
      or aberrant hosts. Sarcocysts are not known to form in aberrant hosts.
      Sarcocystis neurona causes fatal disease in horses (Equine Protozoal
      Myeloencephalitis, EPM). There are numerous reports of fatal EPM-like infections
      in other species, usually with central nervous system signs and associated with
      the schizont stage of S. neurona. Here, we report fatal disseminated S. neurona
      infection in a nine-week-old golden retriever dog from Mississippi, USA.
      Protozoal merozoites were identified in smears of the cerebrospinal fluid.
      Microscopically, lesions and protozoa were identified in eyes, tongue, heart,
      liver, intestines, nasal turbinates, skeletal muscle and brain, which reacted
      intensely with S. neurona polyclonal antibodies. Mature sarcocysts were seen in
      sections of muscles. These sarcocysts were ultrastructurally similar to those of
      S. neurona from experimentally infected animals. These data suggest that the dog
      is another intermediate host for S. neurona. Data suggest that the dog was
      transplacentally infected. 

PMID- 24680605
TI  - Quantification of error in the calculation of Z scores in neonates.

PMID- 24680606
TI  - Silver anniversary-the 25(th) annual scientific sessions.

PMID- 24680608
TI  - From humble beginnings.

PMID- 24680609
TI  - Comment: Delayed cervical esophagogastrostomy: a surgical alternative for
      patients with ischemia of the gastric conduit at time of esophagectomy.

PMID- 24680610
TI  - Benefit or harm: does age matter in stroke outcome after thrombolysis?

PMID- 24680611
TI  - Assessment of intrarenal oxygenation in renal donor with blood oxygenation level
      dependent magnetic resonance imaging.
AB  - OBJECTIVE: To examine change of the apparent relaxation rate R2* values in living
      kidney donors after uninephrectomy using blood oxygenation level-dependent
      magnetic resonance imaging. METHODS: Between July 2011 and January 2012, 45
      kidney donors were enrolled into this study. Blood oxygenation level-dependent
      magnetic resonance imaging scanning was performed before surgery, 3 and 7 days
      postoperatively. Participants were followed up for 1 year. RESULTS: The R2*
      values in medulla (mR2*) were significantly greater than that of cortex (cR2*),
      both in resected kidney and remaining one. cR2* values of the remaining kidney
      was 17.52 +/- 1.36 s(-1) and then decrease significantly by 8.97% to 15.95 +/-
      1.14 s(-1) at 3 days (P <.001) and by 7.82% to 16.15 +/- of 1.05 s(-1) at 7 days.
      No significant modification occurred in mR2* after surgery. Multivariate
      regression analysis showed that the decrease in cR2* values of the remaining
      kidney was positively associated with sex (r = 0.418), body surface area (r =
      0.307), and preoperative cR2* values (r = 0.659). Comparing with glomerular
      filtration rate at 7 days, a further increment in the glomerular filtration rate
      was noted at 1 year in patients with cR2* values decrease of >= 10% at 1 week
      (62.63 +/- 11.69 vs 56.97 +/- 7.51 mL/min/1.73 m(2), P = .02) but not in the
      other patients (66.43 +/- 10.89 vs 62.78 +/- 13.74, P = .064). CONCLUSION: Kidney
      donation will induce early, profound oxygenation modification within the renal
      cortex of the remaining kidney. Donors with cR2* value decrease of >= 10% at 1
      week have a more favorable renal function compensation at 1 year.

PMID- 24680612
TI  - Pinostrobin and Cajanus lactone isolated from Cajanus cajan (L.) leaves inhibits
      TNF-alpha and IL-1beta production: in vitro and in vivo experimentation.
AB  - The tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta)
      inhibitory activities of Cajanus cajan (leaves) crude methanolic extract, its
      fractions and its phytochemical constituents were evaluated in lipopolysaccharide
      (LPS) stimulated RAW 264.7 and J774A.1 cells. Phytochemical investigation of the
      active ethyl acetate (CCE) and n-butanol (CCB) fractions of C. cajan L. leaves
      yielded 14 compounds. It was observed that both pinostrobin (9) and cajanus
      lactone (4) were found to be most active in inhibiting TNF-alpha (IC50<22 MUM)
      and IL-1beta (IC50<40 MUM) whereas compounds 2, 3, 5-8, 10 and 14 showed moderate
      and mild effects (IC50=35.50-81.22 MUM for TNF-alpha and 38.23-89.10 MUM for IL
      1beta) in both the cell lines. Furthermore, at dose of 20mg/kg, both pinostrobin
      (9) and cajanus lactone (4) were found to reduce LPS-induced TNF-alpha levels by
      48.6% and 55.0% respectively and IL-1beta levels by 53.1% and 41.8% respectively
      in Sprague Dawley (SD) rats. These findings suggest that C. cajan L. leaves can
      be developed as an effective herbal remedy for the treatment and prevention of
      inflammation or associated ailments.

PMID- 24680613
TI  - Anti-melanogenic effects of delta-tocotrienol are associated with tyrosinase
      related proteins and MAPK signaling pathway in B16 melanoma cells.
AB  - Tocotrienols are known to possess potent antioxidant, anticancer, and cholesterol
      lowering activities. Being able to rapidly penetrate the skin, these vitamin E
      isoforms have been explored for potential treatment against melanoma. This study
      aimed to elucidate the mechanism involved in the anti-melanogenic effects of
      delta-tocotrienol (deltaT3) in B16 melanoma cells. Results showed that at 20 MUM
      of deltaT3 significantly inhibited melanin formation and ROS generation.
      Treatment with deltaT3 also effectively suppressed the expression of
      melanogenesis-related proteins, including MC1R, MITF, TYRP-1, and TYRP-2. More
      importantly, we observed that the mitogen-activated protein kinase (MAPK) pathway
      was involved in mediating deltaT3's inhibitory effect against melanin production.
      Specifically, deltaT3 treatment markedly induced the activation of extracellular
      signal-regulated kinases (ERK). The use of ERK activation inhibitor (PD98059)
      abrogated the deltaT3-mediated downregulation expression melanogenesis-related
      proteins and restored melanin production. Furthermore, siRNA targeting ERK
      effectively blocked the deltaT3-induced repression of tyrosinase and TYRP-1
      expression. These results suggest that deltaT3's inhibitory effect against
      melanogenesis is mediated by the activation of ERK signaling, thereby resulting
      in downstream repression of melanogenesis-related proteins and the subsequent
      melanin production. These data provide insight to deltaT3's effect and the
      targeting of ERK signaling for treatment against melanogenesis.

PMID- 24680614
TI  - Hypoglycemic and hypolipidemic effects of oxymatrine in high-fat diet and
      streptozotocin-induced diabetic rats.
AB  - Oxymatrine, a quinolizidine alkaloid, has been widely used for the treatment of
      hepatitis. In this study, we investigated the hypoglycemic and hypolipidemic
      effects and new pharmacological activities of oxymatrine, in a high-fat diet and
      streptozotocin (STZ)-induced diabetic rats. The results demonstrated that
      oxymatrine could significantly decrease fasting blood glucose, glycosylated
      hemoglobin (GHb), food and water intake, non-esterified fatty acid (NEFA), total
      cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol levels
      (LDL-c), and increase serum insulin, liver and muscle glycogen, high density
      lipoprotein cholesterol (HDL-c), glucagon-like peptide-1 (GLP-1) and muscle
      glucose transporter-4 (GLUT-4) content in diabetic rats. The results of the
      histological examinations of the pancreas and liver show that oxymatrine
      protected the islet architecture and prevented disordered structure of the liver.
      This study displays that oxymatrine can alleviate hyperglycemia and hyperlipemia
      in a high-fat diet and STZ-induced diabetic rats might by improving insulin
      secretion and sensitivity. 

PMID- 24680615
TI  - Efficacy and safety of Indigo naturalis extract in oil (Lindioil) in treating
      nail psoriasis: a randomized, observer-blind, vehicle-controlled trial.
AB  - Treating nail psoriasis is notoriously difficult and lacks standardized
      therapeutic regimens. Indigo naturalis has been demonstrated to be safe and
      effective in treating skin psoriasis. This trial was conducted to evaluate the
      efficacy and safety of refined indigo naturalis extract in oil (Lindioil) in
      treating nail psoriasis. Thirty-one outpatients with symmetrically comparable
      psoriatic nails were enrolled. Lindioil (experimental group) or olive oil
      (control group) was applied topically to the same subjects' two bilaterally
      symmetrical psoriatic nails twice daily for the first 12 weeks and then subjects
      applied Lindioil to both hands for 12 additional weeks. Outcomes were measured
      using Nail Psoriasis Severity Index (NAPSI) for five nails on one hand and for
      the single most severely affected nail from either hand. The results show a
      reduction of NAPSI scores for the 12-week treatment for the Lindioil group (49.8%
      for one hand and 59.3% for single nail) was superior to the reduction in the
      scores for the control group (22.9%, 16.3%, respectively). There were no adverse
      events during the 24 weeks of treatment. This trial demonstrates that Lindioil is
      a novel, safe and effective therapy for treating nail psoriasis. 

PMID- 24680616
TI  - Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib
      resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein.
AB  - The purpose of this study was to investigate the effects of guggulsterone on
      cyclooxygenase-2 and P-glycoprotein mediated drug resistance in imatinib
      resistant K562 cells (K562/IMA). MTT cytotoxicity assay, flow cytometry, western
      blot analysis, and ELISA were performed to investigate the anti-proliferative
      effect, the reversal action of drug resistance, and the inhibitory effect on
      cyclooxygenase-2, P-glycoprotein, BCR/ABL kinase, and PGE2 release in K562/IMA
      cells by guggulsterone. The results showed that co-administration of
      guggulsterone resulted in a significant increase in chemo-sensitivity of K562/IMA
      cells to imatinib, compared with imatinib treatment alone. Rhodamine123
      accumulation in K562/IMA cells was significantly enhanced after incubation with
      guggulsterone (60, 120 MUM), compared with untreated K562/IMA cells (p<0.05).
      When imatinib (1 MUM) was combined with guggulsterone (60, 120 MUM), the mean
      apoptotic population of K562/IMA cells was 15.47% and 24.91%. It was increased by
      3.82 and 6.79 times, compared with imatinib (1 MUM) treatment alone. Furthermore,
      guggulsterone had significantly inhibitory effects on the levels of
      cyclooxygenase-2, P-glycoprotein and prostaglandin E2. However, guggulsterone had
      little inhibitory effect on the activity of BCR/ABL kinase. The present study
      indicates guggulsterone induces apoptosis by inhibiting cyclooxygenase-2 and down
      regulating P-glycoprotein expression in K562/IMA cells.

PMID- 24680617
TI  - Tetra-acetylajugasterone a new constituent of Vitex cienkowskii with vasorelaxant
      activity.
AB  - Tetra-acetylajugasterone C (TAAC) was found to be one of the naturally occurring
      compounds of the Cameroonian medicinal plant Vitex cienkowskii which is
      responsible for a vasorelaxant activity of an extract of this plant. The
      evaluation of the underlying mechanisms for the relaxing effect of TAAC was
      determined using aortic rings of rats and mice. TAAC produced a concentration
      dependent relaxation in rat artery rings pre-contracted with 1MUM noradrenaline
      (IC50: 8.40MUM) or 60mM KCl (IC50: 36.30MUM). The nitric oxide synthase inhibitor
      l-NAME (100MUM) and the soluble guanylate cyclase inhibitor ODQ (10MUM)
      significantly attenuated the vasodilatory effect of TAAC. TAAC also exerted a
      relaxing effect in aorta of wild-type mice (cGKI(+/+); IC50=13.04MUM) but a
      weaker effect in aorta of mice lacking cGMP-dependent protein kinase I (cGKI(-/
      ); IC50=36.12MUM). The involvement of calcium channels was studied in rings pre
      incubated in calcium-free buffer and primed with 1MUM noradrenaline prior to
      addition of calcium to elicit contraction. TAAC (100MUM) completely inhibited the
      resulting calcium-induced vasoconstriction. The same concentration of TAAC showed
      a stronger effect on the tonic than on the phasic component of noradrenaline
      induced contraction. This study shows that TAAC, a newly detected constituent of
      Vitex cienkowskii contributes to the relaxing effect of an extract of the plant.
      The effect is partially mediated by the involvement of the NO/cGMP pathway of the
      smooth muscle but additionally inhibition of calcium influx into the cell may
      play a role. 

PMID- 24680618
TI  - Anti-tumour and pharmacokinetics study of 2-Formyl-8-hydroxy-quinolinium chloride
      as Galipea longiflora alkaloid analogue.
AB  - The quinolinium chloride salt of 8-hydroxyqinolinecarbaldehyde (2-Formyl-8
      hydroxy-quinolinium chloride) was prepared as Galipea longiflora alkaloid
      analogue and its anticancer activity was evaluated both in vitro and in vivo.
      This chloride salt was found to show certain degree of selectivity between
      hepatoma cells and normal hepatocytes in vitro. Athymic nude mice Hep3B xenograft
      model further demonstrated that this 2-Formyl-8-hydroxy-quinolinium chloride
      could execute strong anti-tumour activity with the identification of extensive
      necrotic feature from the tumour xenograft and limited adverse toxicological
      effect. 

PMID- 24680619
TI  - Gastroprotective effect of epoxy clerodane diterpene isolated from Tinospora
      cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in rats.
AB  - The present study evaluated the gastroprotective effect of epoxy clerodane
      diterpene (ECD), isolated from Tinospora cordifolia on indomethacin-induced
      gastric ulcer in rats. Administration of indomethacin exhibits extreme levels of
      ulcer index (UI) and myeloperoxidase (MPO) activity. Indomethacin down regulated
      PGE2, anti-inflammatory cytokines (IL-4, IL-10) and pro-angiogenic factors (VEGF
      and EGF). The ECD pretreatment considerably increased the levels of PGE2, anti
      inflammatory cytokines and pro-angiogenic factors. The ulcer-healing activity of
      ECD was inhibited by pre-administration of the specific COX-1 inhibitor (SC560)
      and nonspecific NOS inhibitor (L-NAME), which indicates the involvement of PGE2
      and NOS in ECD induced ulcer healing activity. These findings suggest that ECD
      exerts its antiulcer activity by reinforcement of defensive elements and
      diminishing the offensive elements.

PMID- 24680620
TI  - Therapeutic effects of standardized Vitex negundo seeds extract on complete
      Freund's adjuvant induced arthritis in rats.
AB  - The seeds of Vitex negundo L. (Verbenaceae) have been commonly used as a folk
      remedy for the treatment of rheumatism and joint inflammation in Traditional
      Chinese Medicine. This study aimed to evaluate the anti-arthritic activity of the
      extract of V. negundo seeds (EVNS) using Freund's complete adjuvant (CFA) induced
      arthritis (AA) in rat model. As a result, EVNS, with abundant phenylnaphthalene
      type lignans, significantly inhibited the paw edema, decreased the arthritis
      score and spleen index, and reversed the weight loss of CFA-injected rats.
      Histopathological studies showed a marked decrease of synovial inflammatory
      infiltration and synovial lining hyperplasia in the joints of EVNS-treated
      animals. The remarkable decrement of serum inflammatory factors (TNF-alpha, IL
      1beta and IL-6) were observed in EVNS-treated rats, whereas, IL-10, an anti
      inflammatory cytokine, was found to be significantly increased by EVNS. The
      expressions of COX-2 and 5-LOX in PBMC were also inhibited by administration of
      EVNS. Our results demonstrated that V. negundo seeds possessed potential
      therapeutic effect on adjuvant induced arthritis in rats by decreasing the levels
      of TNF-alpha, IL-1beta and IL-6 and increasing that of IL-10 in serum as well as
      down-regulating the levels of COX-2 and 5-LOX, and therefore may be an effective
      cure for the treatment of human rheumatoid arthritis. 

PMID- 24680621
TI  - Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men:
      a randomized, double-blind, placebo-controlled clinical trial.
AB  - In recent years, wide utilization of herbal drugs has encouraged scientists to
      determine their impressive effects on health. Since Nigella sativa L. seed (N.
      sativa) has many uses including infertility in traditional medicine, the effects
      of Nigella sativa L. seed oil on abnormal semen quality in infertile men with
      abnormal semen quality are of interest. This study was conducted on Iranian
      infertile men with inclusion criteria of abnormal sperm morphology less than 30%
      or sperm counts below 20*10(6)/ml or type A and B motility less than 25% and 50%
      respectively. The patients in N. sativa oil group (n=34) received 2.5mlN. sativa
      oil and placebo group (n=34) received 2.5ml liquid paraffin two times a day
      orally for 2 months. At baseline and after 2 months, the sperm count, motility
      and morphology and semen volume, pH and round cells as primary outcomes were
      determined in both groups. Results showed that sperm count, motility and
      morphology and semen volume, pH and round cells were improved significantly in N.
      sativa oil treated group compared with placebo group after 2 months. It is
      concluded that daily intake of 5ml N. sativa oil for two months improves abnormal
      semen quality in infertile men without any adverse effects. 

PMID- 24680623
TI  - Perceptions of health status and survival in patients with metastatic lung
      cancer.
AB  - CONTEXT: Cognitive awareness of having a terminal illness is associated with
      critical treatment decisions and outcomes. However, little is known about the
      course and correlates of such perceptions in patients with metastatic lung
      cancer. OBJECTIVES: We explored changes in perceptions of health status over time
      in patients with metastatic non-small cell lung cancer (NSCLC) and whether
      awareness of having a terminal illness was associated with survival. METHODS: For
      this secondary analysis of clinical trial data, we assessed perceptions of health
      status at baseline, 12, 18, and 24 weeks. At each time point, patients with
      metastatic NSCLC completed a measure of quality of life (Functional Assessment of
      Cancer Therapy-Trial Outcome Index) and also reported whether they were
      "relatively healthy," "seriously but not terminally ill," or "seriously and
      terminally ill." We reviewed patients' medical records to gather data on clinical
      characteristics. RESULTS: At baseline, 49.3% reported being relatively healthy,
      whereas the remainder self-identified as seriously but not terminally ill (38.2%)
      or seriously and terminally ill (12.5%). Over multiple assessments, 24.8%
      reported having a terminal illness. Adjusting for known prognostic factors,
      patients' time-varying perceptions of health status remained a significant
      predictor of survival (hazards ratio = 1.50, 95% CI = 1.07-2.09, P = 0.019).
      CONCLUSION: A minority of patients with metastatic NSCLC acknowledged being
      terminally ill. Those reporting that they were seriously and terminally ill had
      shorter survival compared with those who did not consider themselves terminally
      ill, even after adjusting for decline in physical and functional well-being.

PMID- 24680622
TI  - The alkaloid matrine of the root of Sophora flavescens prevents arrhythmogenic
      effect of ouabain.
AB  - Matrine, a alkaloid of the root of Sophora flavescens, has multiple protective
      effects on the cardiovascular system including cardiac arrhythmias. However, the
      molecular and ionic mechanisms of matrine have not been well investigated. Our
      study aimed at to shed a light on the issue to investigate the antiarrhythmic
      effects of matrine by using ouabain to construct an arrhythmic model of
      cardiomyocytes. In this experiment, matrine significantly and dose-dependently
      increased the doses of ouabain required to induce cardiac arrhythmias and
      decreased the duration of arrhythmias in guinea pigs. In cardiomyocytes of guinea
      pigs, ouabain 10 MUM prolonged action potential duration by 80% (p<0.05) and
      increased L-type Ca(2+) currents and Ca(2+) transients induced by KCl (p<0.05).
      Matrine 100 MUM shortened the prolongation of APD and prevented the increase of L
      type Ca(2+) currents and Ca(2+) transients induced by ouabain. Taken together,
      these findings provide the first evidence that matrine possessed arrhythmogenic
      effect of ouabain by inhibiting of L-type Ca(2+) currents and Ca(2+) overload in
      guinea pigs.

PMID- 24680624
TI  - Care evaluation scale-patient version: measuring the quality of the structure and
      process of palliative care from the patient's perspective.
AB  - CONTEXT: Recently, greater emphasis has been placed on patient-reported outcomes.
      However, there are only a few measures to evaluate the quality of care from the
      patient's perspective. OBJECTIVES: To report the development of a scale to
      measure the quality of the structure and process in palliative care from the
      patient's perspective and examine the reliability and validity of the scale.
      METHODS: A cross-sectional anonymous questionnaire was administered to cancer
      patients who were being treated on an oncology inpatient ward, who visited an
      oncology outpatient clinic at Saitama Medical University International Medical
      Center, or who were in an inpatient palliative unit in Japan between August 2007
      and March 2008. RESULTS: A total of 405 cancer patients participated in the
      study. Factor analysis revealed that the Care Evaluation Scale-Patient version
      (CES-P) consisted of 23 items with eight subscales: physical care by physicians,
      physical care by nurses, psychoexistential care, help with decision making for
      patients, environment, cost, availability, and coordination/consistency. The
      total CES-P score was correlated with satisfaction (r = 0.63) but not with
      quality of life (r = 0.18). The Cronbach alpha coefficient of the total score was
      0.97, and the intraclass correlation coefficient of the total score was 0.67. The
      CES-P total score was not significantly correlated with the self-reported Eastern
      Cooperative Oncology Group performance status (rho = -0.05). CONCLUSION: The CES
      P has sufficient validity and reliability. In addition, this scale is independent
      of the general physical condition of the patient.

PMID- 24680625
TI  - Research priorities in spiritual care: an international survey of palliative care
      researchers and clinicians.
AB  - CONTEXT: Spiritual distress, including meaninglessness and hopelessness, is
      common in advanced disease. Spiritual care is a core component of palliative
      care, yet often neglected by health care professionals owing to the dearth of
      robust evidence to guide practice. OBJECTIVES: To determine research priorities
      of clinicians/researchers and thus inform future research in spiritual care in
      palliative care. METHODS: An online, cross-sectional, mixed-methods survey was
      conducted. Respondents were asked whether there is a need for more research in
      spiritual care, and if so, to select the five most important research priorities
      from a list of 15 topics. Free-text questions were asked about additional
      research priorities and respondents' single most important research question,
      with data analyzed thematically. RESULTS: In total, 971 responses, including 293
      from palliative care physicians, 112 from nurses, and 111 from chaplains, were
      received from 87 countries. Mean age was 48.5 years (standard deviation, 10.7),
      64% were women, and 65% were Christian. Fifty-three percent reported their work
      as "mainly clinical," and less than 2.5% stated that no further research was
      needed. Integrating quantitative and qualitative data demonstrated three priority
      areas for research: 1) development and evaluation of conversation models and
      overcoming barriers to spiritual care in staff attitudes, 2) screening and
      assessment, and 3) development and evaluation of spiritual care interventions and
      determining the effectiveness of spiritual care. CONCLUSION: In this first
      international survey exploring researchers' and clinicians' research priorities
      in spiritual care, we found international support for research in this domain.
      Findings provide an evidence base to direct future research and highlight the
      particular need for methodologically rigorous evaluation studies.

PMID- 24680626
TI  - Clinic-based outpatient palliative care before hospice is associated with longer
      hospice length of service.
AB  - CONTEXT: Outpatient nonhospice palliative care has been shown to provide many
      benefits to patients facing advanced illness, but such services remain uncommon
      in the U.S. Little is known about the association between clinic-based outpatient
      palliative care consultation and the timing of hospice enrollment. OBJECTIVES: To
      determine whether there are differences in hospice length of service (LOS)
      between patients who were seen vs. patients who were not seen in an outpatient
      palliative care clinic before enrollment in hospice. METHODS: Using a
      retrospective study of medical records, a "prior palliative care clinic" group
      was formed of those hospice patients who had had a nonhospice clinic-based
      outpatient palliative care consult before hospice admission (n = 354). For those
      patients, "control" hospice patients without prior clinic-based palliative care
      were chosen who were matched by age, gender, median income of their zip code, and
      diagnostic group. Both groups were restricted to patients who died while enrolled
      in hospice. LOS for these two groups was compared using standard statistical
      methods of survival analysis. RESULTS: Prior palliative care clinic patients had
      a median LOS of 24 days, whereas control patients had a median LOS of 15 days
      (95% CI for difference between the medians 5-13 days). The difference between the
      LOS distribution curves was statistically significant by the log-rank test (P <
      0.001). CONCLUSION: Hospice patients who had clinic-based outpatient palliative
      consults before hospice enrollment tended, on average, to have a longer LOS in
      hospice than patients who did not.

PMID- 24680627
TI  - Measurement and invariance characteristics of psychosocial correlates of youth
      physical activity.
AB  - OBJECTIVES: Physical inactivity needs to be strategically addressed from and
      throughout childhood and adolescence. The youth physical activity promotion model
      provides a comprehensive framework for understanding and promoting physical
      activity in youth. This study examined psychometric characteristics of the
      children's attraction to physical activity scale and the perceived physical
      competence scale, two frequently utilized instruments to measure the underlying
      predisposing factors emphasized in the youth physical activity promotion model.
      DESIGN: A cross-sectional correlational research design was utilized to address
      the research purposes. METHODS: Participants (N=1563) were involved with a large
      school-based initiative involving 19 schools in two U.S. states. The children's
      attraction to physical activity and perceived physical competence scales were
      administered in the schools by the physical education teachers using a customized
      online platform. Confirmatory factory analysis and invariance model testing
      (i.e., configural, metric, and scalar invariances) were conducted with the Linear
      Structural Relations 8.8 software. RESULTS: The results supported the
      multidimensionality of the children's attraction to physical activity scale and
      demonstrated that the 6-factor measurement model was invariant by gender and
      mostly invariant by school level (elementary, middle, high). The scalar non
      invariance across school levels was attributed to weak psychometric properties in
      two of the children's attraction to physical activity subscales (i.e., peer
      acceptance and fun of physical exertion). CONCLUSIONS: The findings support the
      utility of the children's attraction to physical activity and perceived physical
      competence for capturing predisposing factors within the youth physical activity
      promotion model but document the need for refinements in several key subscales.

PMID- 24680628
TI  - Advocating for opioid substitution therapy in Central Asia: much still to be
      done.
AB  - Opioid substitution therapy (OST) was first introduced in the formerly-Soviet
      Central Asian Republics as an HIV prevention intervention for people who inject
      drugs (PWID) in 2002. Presently, pilot programs function in Kazakhstan and
      Tajikistan, and Kyrgyzstan has scaled-up from the pilot phase to the operation of
      over 20 OST sites nation-wide. All three countries have taken steps towards lower
      threshold programs, allowing clients to enroll regardless of HIV status, and, in
      some cases, without documentation of failure to complete other drug treatment
      programs. However, OST programs remain exclusively funded by international
      donors, and political and societal opposition to these programs threaten their
      stability. In order to counter negative campaigns and political attacks on OST,
      organized advocacy efforts are needed. This commentary explores efforts
      undertaken by international donor partners supporting advocacy efforts to scale
      up OST and assure a sustainable future for programming. It examines both
      proactive and reactive efforts, and the variety of target audiences that need to
      be reached to conduct effective advocacy. Ultimately we find that, while a range
      of tools are available for OST advocacy in the hostile environments of the former
      Soviet Union, the strengthening of advocacy groups is needed to assure an
      optimized platform exists for using the evidence and developing relevant
      materials in the appropriate languages (including, but not limited to, Russian)
      for both proactive and reactive efforts; and that more robust monitoring is
      desirable to bring sharper focus to replicable methods. 

PMID- 24680629
TI  - Prevalence and severity of ventricular dysfunction in patients with HIV-related
      pulmonary arterial hypertension.
AB  - OBJECTIVES: To evaluate the occurrence of ventricular systolic dysfunction in
      human immunodeficiency virus (HIV)-related pulmonary arterial hypertension (PAH).
      BACKGROUND: Patients with HIV-related PAH may develop ventricular systolic
      dysfunction both as a consequence of PAH progression or of the myocardial
      involvement from the HIV infection itself. METHODS: Cardiac magnetic resonance
      imaging was applied to measure ejection fraction for the left ventricle and the
      right ventricle in patients with HIV-related PAH (n = 27) and in patients with
      PAH from other aetiologies (n = 115). RESULTS: In HIV-related PAH, ejection
      fraction values were lower and a higher proportion of patients presented with an
      advanced stage of ventricular dysfunction (55% vs. 25%; p = 0.009). In a
      multivariate model, PAH related to HIV infection remained independently
      associated with advanced ventricular dysfunction (p = 0.011). CONCLUSIONS:
      Patients with HIV-related PAH have more prevalent and severe ventricular systolic
      dysfunction compared to patients with PAH from other aetiologies.

PMID- 24680630
TI  - Relative's experiences before and after a heart or lung transplantation.
AB  - BACKGROUND: Relatives take on great responsibilities during patients' heart or
      lung transplant process and an understanding for their situation is required.
      OBJECTIVE: To describe relative's experiences before and during the patient's
      hospital stay as well as during the first 6 months after a heart or lung
      transplantation. METHODS: Using qualitative content analysis, 15 relatives (eight
      women and seven men) aged 36-65 years were interviewed within 6 months of a heart
      or lung transplantation. RESULT: Three categories that illuminate relatives'
      experiences have been identified: "Navigate specific circumstances," "Facilitate
      throughout the transplantation journey" and "Experiences of strength and weakness
      of information and support." The relatives reported involvement in the
      transplantation decision, peer support, information seeking, burden and coping.
      CONCLUSION: Greater awareness about relatives' experiences with identification of
      appropriate support and information exchange between health care professionals
      and relatives is important. This awareness could provide benefits for heart or
      lung transplant patients, families and health care organizations.

PMID- 24680631
TI  - Cervical osteophyte causing cerebellar infarction.

PMID- 24680632
TI  - Smoke-free policies: cleaning the air with money to spare.

PMID- 24680633
TI  - Effect of smoke-free legislation on perinatal and child health: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Smoke-free legislation has the potential to reduce the substantive
      disease burden associated with second-hand smoke exposure, particularly in
      children. We investigated the effect of smoke-free legislation on perinatal and
      child health. METHODS: We searched 14 online databases from January, 1975 to May,
      2013, with no language restrictions, for published studies, and the WHO
      International Clinical Trials Registry Platform for unpublished studies.
      Citations and reference lists of articles of interest were screened and an
      international expert panel was contacted to identify additional studies. We
      included studies undertaken with designs approved by the Cochrane Effective
      Practice and Organisation of Care that reported associations between smoking bans
      in workplaces, public places, or both, and one or more predefined early-life
      health indicator. The primary outcomes were preterm birth, low birthweight, and
      hospital attendances for asthma. Effect estimates were pooled with random-effects
      meta-analysis. This study is registered with PROSPERO, number CRD42013003522.
      FINDINGS: We identified 11 eligible studies (published 2008-13), involving more
      than 2.5 million births and 247,168 asthma exacerbations. All studies used
      interrupted time-series designs. Five North American studies described local bans
      and six European studies described national bans. Risk of bias was high for one
      study, moderate for six studies, and low for four studies. Smoke-free legislation
      was associated with reductions in preterm birth (four studies, 1,366,862
      individuals; -10.4% [95% CI -18.8 to -2.0]; p=0.016) and hospital attendances for
      asthma (three studies, 225,753 events: -10.1% [95% CI -15.2 to -5.0]; p=0.0001).
      No significant effect on low birthweight was identified (six studies, >1.9
      million individuals: -1.7% [95% CI -5.1 to 1.6]; p=0.31). INTERPRETATION: Smoke
      free legislation is associated with substantial reductions in preterm births and
      hospital attendance for asthma. Together with the health benefits in adults, this
      study provides strong support for WHO recommendations to create smoke-free
      environments. FUNDING: Thrasher Fund, Lung Foundation Netherlands, International
      Paediatric Research Foundation, Maastricht University, Commonwealth Fund.

PMID- 24680634
TI  - Validation of the InCaSaQ, a new tool for the evaluation of patient satisfaction
      with clean intermittent self-catheterization.
AB  - AIMS: In neurourology, the choice of catheter is of paramount importance. At the
      time of our study, no simple validated questionnaire has been published,
      evaluating patient satisfaction with the use of urinary catheters. Our objective
      was to construct and validate a specific tool referred to as the Intermittent
      Catheterization Satisfaction Questionnaire (InCaSaQ), for the purposes of
      evaluating patient satisfaction with intermittent self-catheterization. METHODS:
      A simple tool was developed and validated in a neurourology referral centre, with
      113 patients affected by a neurological bladder condition, between November 2011
      and February 2012. Eight items, separated into four categories ("packaging",
      "lubrication", "catheter itself", "after catheterization") were selected. The
      mean score obtained with the eight-question questionnaire was calculated for each
      patient. Face validity was evaluated. Reliability based on internal consistency
      and test-retest reliability using the intraclass correlation coefficient (ICC)
      was carried out. RESULTS: The patients' comprehension and acceptance of the
      questionnaire were good. The questionnaire appears to have been well designed,
      with a significant Cronbach's alpha coefficient, and the ICC demonstrated good
      test-retest reliability. CONCLUSIONS: The InCaSaQ was found to be a valid tool
      for the evaluation of patient satisfaction with a urinary catheter. It is thus
      possible to compare the comfort and effectiveness of different types of catheter,
      and to objectify the need to change the type of catheter, in cases where patients
      express their dissatisfaction.

PMID- 24680635
TI  - Atypical motor behavior in a poststroke subject with agenesis of the corpus
      callosum: a case report.

PMID- 24680636
TI  - Club foot revealing a hypoplasia of the navicular bone: the first case report.

PMID- 24680637
TI  - Carcinoma cuniculatum: an atypical presentation in the foot.
AB  - Carcinoma cuniculatum is a rarely occurring, low-grade variant of squamous cell
      carcinoma most commonly found in the forefoot. It should be suspected in the
      differential diagnosis for chronic nonhealing verrucous wounds. The initial
      diagnosis of carcinoma cuniculatum is difficult and often delayed and can require
      repeated histopathologic evaluation by an experienced pathologist. In many cases,
      the final diagnosis will be made from the microscopic findings correlated with
      the clinical examination findings. Metastasis from carcinoma cuniculatum is rare,
      although it can invade deep into the soft tissues and can extend to the bone.
      Wide local excision with a 5-mm tumor-free margin has been the recommended
      treatment. If the tumor extends into the bone, amputation might be warranted. The
      present report describes the case of an atypical carcinoma cuniculatum found in
      the hindfoot of an adult female and represents the surgical follow-up to the
      histopathologic description of the same patient's lesion as previously described
      in a published report. 

PMID- 24680638
TI  - Paediatric lung recruitment: a review of the clinical evidence.
AB  - Lung recruitment is used as an adjunct to lung protective ventilation strategies.
      Lung recruitment is a brief, deliberate elevation of transpulmonary pressures
      beyond what is achieved during tidal ventilation levels. The aim of lung
      recruitment is to maximise the number of alveoli participating in gas exchange
      particularly in distal and dependant regions of the lung. This may improve
      oxygenation and end expiratory levels. Restoration of end expiratory levels and
      stabilisation of the alveoli may reduce the incidence of ventilator induced lung
      injury (VILI). Various methods of lung recruitment have been studied in adult and
      experimental populations. This review aims to establish the evidence for lung
      recruitment in the pediatric population. 

PMID- 24680639
TI  - Assessment of time-frequency representation techniques for thoracic sounds
      analysis.
AB  - A step forward in the knowledge about the underlying physiological phenomena of
      thoracic sounds requires a reliable estimate of their time-frequency behavior
      that overcomes the disadvantages of the conventional spectrogram. A more detailed
      time-frequency representation could lead to a better feature extraction for
      diseases classification and stratification purposes, among others. In this
      respect, the aim of this study was to look for an omnibus technique to obtain the
      time-frequency representation (TFR) of thoracic sounds by comparing generic
      goodness-of-fit criteria in different simulated thoracic sounds scenarios. The
      performance of ten TFRs for heart, normal tracheal and adventitious lung sounds
      was assessed using time-frequency patterns obtained by mathematical functions of
      the thoracic sounds. To find the best TFR performance measures, such as the 2D
      local (rho(mean)) and global (rho) central correlation, the normalized root-mean
      square error (NRMSE), the cross-correlation coefficient (rho(IF)) and the time
      frequency resolution (res(TF)) were used. Simulation results pointed out that the
      Hilbert-Huang spectrum (HHS) had a superior performance as compared with other
      techniques and then, it can be considered as a reliable TFR for thoracic sounds.
      Furthermore, the goodness of HHS was assessed using noisy simulated signals.
      Additionally, HHS was applied to first and second heart sounds taken from a young
      healthy male subject, to tracheal sound from a middle-age healthy male subject,
      and to abnormal lung sounds acquired from a male patient with diffuse
      interstitial pneumonia. It is expected that the results of this research could be
      used to obtain a better signature of thoracic sounds for pattern recognition
      purpose, among other tasks.

PMID- 24680640
TI  - The frequency and nature of resolution of potential police provoked shooting
      encounters.
AB  - Helping people in acute psychiatric crisis has become an increasingly common part
      of modern community policing. In certain extreme cases, police may be faced with
      a suicidal individual who intends to intentionally provoke police to shoot them.
      While fatalities are fortunately rare, anecdotal reports from frontline police
      suggest that these kinds of encounters are occurring on a regular basis. This
      paper explores 2350 psychiatric crisis incidents over an eight-month period in
      Victoria, Australia, and assesses the frequency and nature of potential police
      provoked shootings resolved through non-fatal means. Contextual factors relating
      to the person's behaviour and police responses, and the person's psychiatric and
      criminal histories were considered to elucidate characteristics common to these
      incidents. Results suggest that police are potentially encountering a person who
      is suicidal and trying to provoke police to shoot them more than twice a week.
      These individuals share a number of common characteristics with those who have
      been fatally shot in similar circumstances and are quite different from those who
      attempt self-inflicted suicide. Results are discussed in relation to the impact
      of previous criminal contact from both the suspect and police perspectives. 

PMID- 24680641
TI  - Walking the line: specialized and standard probation officer perspectives on
      supervising probationers with serious mental illnesses.
AB  - Specialized probation programs were developed to more effectively address the
      unique needs of probationers with serious mental illnesses. Probation officers
      are tasked with serving both law enforcement and rehabilitative functions, and
      officers play an important gatekeeper function in helping probationers with
      serious mental illnesses avoid long incarceration sentences. The purpose of this
      paper was to explore specialized and standard probation officers' work in
      supervising probationers with serious mental illnesses. Twenty-one probation
      officers (11 specialized and 10 standard) participated in semi-structured
      interviews. Qualitative analyses examined: 1 - beliefs on the relationship
      between mental illness and crime; 2 - purpose of specialized and standard
      probation units; and 3 - approaches to supervising probationers with serious
      mental illnesses. Implications for developing more effective probation
      supervision programs are discussed. 

PMID- 24680642
TI  - Expression of estrogen receptors, androgen receptor and steroid receptor
      coactivator-3 is negatively correlated to the differentiation of astrocytic
      tumors.
AB  - Astrocytic tumors are the most common primary brain tumors. It has been reported
      that androgen receptor (AR), estrogen receptors alpha (ERalpha) and beta (ERbeta)
      and their coactivator SRC-1 and SRC-3 are involved in the regulation of the
      growth and development of many tumors, but their expression profiles and
      significances in the astrocytic tumors remain largely unknown. In this study, the
      expression of AR, ERs, and SRCs, and the possible roles of them in astrocytic
      neoplasm were evaluated and compared to normal brain tissues by nickel
      intensified immunohistochemistry with tissue microarrays. The results showed that
      there were no age- or gender-differences regarding to the levels of these
      receptors or coactivators in astrocytic or normal brain tissues. In the high
      grade astrocytic tissue, the levels of AR, ERs and SRC-3 were significantly
      decreased when compared to the low-grade astrocytic tissues, but the levels of
      SRC-1 remain unchanged. Correlation analysis revealed that the levels of AR, ERs
      and SRC-3 were negatively correlated to tumor differentiation, and the levels of
      SRC-3 were positively correlated to that of ERalpha. Furthermore, the decreased
      levels of SRC-3 were associated with an increase of ERbeta in astrocytic tumors
      when compared to that of normal brain tissues. These above results indicate a
      combination of decreased expression of ERs, AR and SRC-3 but not SRC-1 may be
      involved in the tumorigenesis of gliomas, ERalpha/SRC-3 axis may play central
      role in the regulation these tumors. 

PMID- 24680643
TI  - Survival of cancer patients in urban and rural areas of Germany--a comparison.
AB  - BACKGROUND: Cancer care services including cancer prevention activities are
      predominantly localised in central cities, potentially causing a heterogeneous
      geographic access to cancer care. The question of an association between
      residence in either urban or rural areas and cancer survival has been analysed in
      other parts of the world with inconsistent results. This study aims at a
      comparison of age-standardised 5-year survival of cancer patients resident in
      German urban and rural regions using data from 11 population-based cancer
      registries covering a population of 33 million people. MATERIAL AND METHODS:
      Patients diagnosed with cancers of the most frequent and of some rare sites in
      1997-2006 were included in the analyses. Places of residence were assigned to
      rural and urban areas according to administrative district types of settlement
      structure. Period analysis and district type specific population life tables were
      used to calculate overall age-standardised 5-year relative survival estimates for
      the period 2002-2006. Poisson regression models for excess mortality (relative
      survival) were used to test for statistical significance. RESULTS: The 5-year
      relative survival estimates varied little among district types for most of the
      common sites with no consistent trend. Significant differences were found for
      female breast cancer patients and male malignant melanoma patients resident in
      city core regions with slightly better survival compared to all other district
      types, particularly for patients aged 65 years and older. CONCLUSION: With regard
      to residence in urban or rural areas, the results of our study indicate that
      there are no severe differences concerning quality and accessibility of
      oncological care in Germany among different district types of settlement.

PMID- 24680644
TI  - Comparing temporal trends of organochlorines in guillemot eggs and Baltic
      herring: advantages and disadvantage for selecting sentinel species for
      environmental monitoring.
AB  - Within Europe, the Marine Strategy Framework Directive (MSFD) is aimed at
      addressing the chemical status and quality of the marine environment. One of the
      main goals is to achieve Good Environmental Status (GES) in the marine
      environment. Environmental monitoring of biota e.g., Baltic herring and guillemot
      eggs, is conducted annually in Sweden to follow temporal changes in environmental
      contaminants. To determine the suitability of guillemot eggs as a sentinel
      species for investigating GES, we compared temporal trends of polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated
      biphenyls (dl-PCBs) in these two species from single sampling sites within
      Sweden. Lipid content from guillemot eggs was consistently high and stable
      (yearly mean for >40 years, ~12%) compared to that of herring (yearly mean for
      >20 years, ~3%). A significant decreasing trend of SigmaPCDD/F in TEQ WHO1998 was
      observed in guillemot eggs, but no trend was seen in herring. CB118 significantly
      decreased in both species, but in the last 10 years this decrease was not
      significant in herring. A number of advantages, such as high lipid content in the
      egg and a low coefficient of variation make guillemot suitable as a sentinel
      species. The advantages and disadvantages of using either guillemot eggs or
      Baltic herring are compared. 

PMID- 24680645
TI  - Mathematical modeling the pathway of human breast cancer.
AB  - In order to understand the mechanism of human breast cancer we use the growth
      rates of clonal expansion of intermediate cells and mutation rates as parameters
      and build two-six stage models to fit the age-specific incidence of breast
      cancers in the surveillance, epidemiology, and end results (SEER) registry. We
      propose four types of different mechanisms for the human breast cancer and test
      those mechanisms by Chi-square test. Our results suggest that loss of functions
      of instability genes is an early event in the tumorigenesis, which is useful for
      early diagnosis of breast cancer. The clonal expansion of intermediate cells must
      depend on the hormone expression level of females, which implies that it may be
      effective for females to receive hormone blocking therapy for breast cancer
      before their menopause. 

PMID- 24680647
TI  - The immunomodulating role of exercise in metabolic disease.
AB  - A lack of physical activity is linked to the development of many chronic
      diseases. It is now well established that the immune system and inflammation play
      a central role in the development of numerous chronic metabolic diseases
      including insulin resistance, type 2 diabetes, atherosclerosis, nonalcoholic
      fatty liver disease, and specific types of cancer. Physical exercise elicits
      potent anti-inflammatory effects that are likely to account for many of the
      salutary actions of regular exercise on chronic metabolic diseases. Here we
      review the anti-inflammatory and immunomodulatory mechanisms by which the
      beneficial effects of exercise on chronic metabolic diseases may be mediated. 

PMID- 24680648
TI  - Menopausal hormone treatment cardiovascular disease: another look at an
      unresolved conundrum.
AB  - Cardiovascular disease (CVD) is the most common cause of death in women. Before
      the Women's Health Initiative (WHI) hormone trials, evidence favored the concept
      that menopausal hormone treatment (MHT) protects against CVD. WHI studies failed
      to demonstrate CVD benefit, with worse net outcomes for MHT versus placebo in the
      population studied. We review evidence regarding the relationship between MHT and
      CVD with consideration of mechanisms and risk factors for atherogenesis and
      cardiac events, results of observational case-control and cohort studies, and
      outcomes of randomized trials. Estrogen effects on CVD risk factors favor delay
      or amelioration of atherosclerotic plaque development but may increase risk of
      acute events when at-risk plaque is present. Long-term observational studies have
      shown ~40% reductions in risk of myocardial infarction and all-cause mortality.
      Analyses of data from randomized control trials other than the WHI show a ~30%
      cardioprotective effect in recently menopausal women. Review of the literature as
      well as WHI data suggests that younger and/or more recently menopausal women may
      have a better risk-benefit ratio than older or remotely menopausal women and that
      CVD protection may only occur after >5 years; WHI women averaged 63 years of age
      (12 years postmenopausal) and few were studied for >6 years. Thus, a beneficial
      effect of long-term MHT on CVD and mortality is still an open question and is
      likely to remain controversial for the foreseeable future.

PMID- 24680646
TI  - On heart rate variability and autonomic activity in homeostasis and in systemic
      inflammation.
AB  - Analysis of heart rate variability (HRV) is a promising diagnostic technique due
      to the noninvasive nature of the measurements involved and established
      correlations with disease severity, particularly in inflammation-linked
      disorders. However, the complexities underlying the interpretation of HRV
      complicate understanding the mechanisms that cause variability. Despite this,
      such interpretations are often found in literature. In this paper we explored
      mathematical modeling of the relationship between the autonomic nervous system
      and the heart, incorporating basic mechanisms such as perturbing mean values of
      oscillating autonomic activities and saturating signal transduction pathways to
      explore their impacts on HRV. We focused our analysis on human endotoxemia, a
      well-established, controlled experimental model of systemic inflammation that
      provokes changes in HRV representative of acute stress. By contrasting modeling
      results with published experimental data and analyses, we found that even a
      simple model linking the autonomic nervous system and the heart confound the
      interpretation of HRV changes in human endotoxemia. Multiple plausible
      alternative hypotheses, encoded in a model-based framework, equally reconciled
      experimental results. In total, our work illustrates how conventional assumptions
      about the relationships between autonomic activity and frequency-domain HRV
      metrics break down, even in a simple model. This underscores the need for further
      experimental work towards unraveling the underlying mechanisms of autonomic
      dysfunction and HRV changes in systemic inflammation. Understanding the extent of
      information encoded in HRV signals is critical in appropriately analyzing prior
      and future studies. 

PMID- 24680650
TI  - Current recommendations: what is the clinician to do?
AB  - Menopausal hormone therapy (HT) has complex biologic effects but continues to
      have an important clinical role in the management of vasomotor and other
      menopausal symptoms. The rational use of menopausal HT requires balancing the
      potential benefits and risks of treatment. Findings from the Women's Health
      Initiative (WHI) and other randomized clinical trials have helped to clarify the
      benefits and risks of HT and have provided insights to improve decision making.
      Several clinical characteristics have utility in identifying women for whom
      benefits of HT are likely to outweigh the risks. Age and time since menopause are
      strong predictors of health outcomes and absolute risks associated with HT, and
      differences by age have been particularly apparent for estrogen alone. In the WHI
      trial of conjugated equine estrogens (CEE) alone, younger women (50-59 years) had
      more favorable results for all-cause mortality, myocardial infarction, and the
      global index, but not for stroke and venous thrombosis. Age trends were less
      clear for CEE + medroxyprogesterone acetate, owing to increased risks of breast
      cancer, stroke, and venous thrombosis in all age groups. Absolute risks of
      adverse events were lower in younger than in older women in both trials, however.
      Other predictors of lower vascular risk from HT include favorable lipid status
      and absence of the metabolic syndrome. Transdermal administration may be
      associated with lower risks of venous thrombosis and stroke, but additional
      research is needed. The use of risk stratification and personalized risk
      assessment offers promise for improved benefit-risk profile and safety of HT. One
      approach to decision making is presented. Key elements include: assessment of
      whether the patient has moderate to severe menopausal symptoms, the primary
      indication for initiating systemic HT (vaginal estrogen may be used to treat
      genitourinary symptoms in the absence of vasomotor symptoms); understanding the
      patient's own preference regarding therapy; evaluating the patient for the
      presence of any contraindications to HT, as well as the time since menopause
      onset and baseline risks of cardiovascular disease and breast cancer; reviewing
      carefully the benefits and risks of treatment with the patient, giving more
      emphasis to absolute than to relative measures of effect; and, if HT is
      initiated, regularly reviewing the patient's need for continued treatment.

PMID- 24680651
TI  - Evaluations of a mechanistic hypothesis for the influence of extracellular ions
      on electroporation due to high-intensity, nanosecond pulsing.
AB  - The effect of ions present in the extracellular medium on electroporation by high
      intensity, short-duration pulsing is studied through molecular dynamic
      simulations. Our simulation results indicate that mobile ions in the medium might
      play a role in creating stronger local electric fields across membranes that then
      reinforce and strengthen electroporation. Much faster pore formation is predicted
      in higher conductivity media. However, the impact of extracellular conductivity
      on cellular inflows, which depend on transport processes such as electrophoresis,
      could be different as discussed here. Our simulation results also show that
      interactions between cations (Na(+) in this case) and the carbonyl oxygen of the
      lipid headgroups could impede pore resealing. 

PMID- 24680649
TI  - Effects of hormone therapy on cognition and mood.
AB  - OBJECTIVE: Results of the Women's Health Initiative (WHI) and Women's Health
      Initiative Memory Study (WHIMS) suggested that hormone therapy (HT) may be
      detrimental to cognitive health. This article reviews clinical studies that
      address issues relevant to those results. DESIGN: Literature review.
      INTERVENTION(S): A search of Pubmed and Web of Science was conducted using the
      search terms HT and cognition, HT and mood. Clinical and observational studies
      were selected if they were published after the year 2000. Theories of HT
      mechanisms of action, pharmacology, biology, and observational and clinical
      trials are discussed. RESULT(S): Although observational and clinical trials show
      conflicting findings, methodologic considerations must be acknowledged. HT
      formulation and dose, route of administration, timing of initiation, length of
      treatment, and health of participants all contribute to inconsistencies in
      results. Transdermal estradiol and micronized progesterone administered at time
      of menopause are generally associated with cognitive and affective benefit.
      CONCLUSION(S): At the present time, results from existing studies are equivocal
      regarding the benefits of HT on cognition and affect. Future studies, such as the
      Kronos Early Estrogen Prevention Study (KEEPS), should address methodologic
      inconsistencies to provide clearer answers to this important question.

PMID- 24680652
TI  - Isolation and characterization of the plasma membrane from the yeast Pichia
      pastoris.
AB  - Despite similarities of cellular membranes in all eukaryotes, every compartment
      displays characteristic and often unique features which are important for the
      functions of the specific organelles. In the present study, we biochemically
      characterized the plasma membrane of the methylotrophic yeast Pichia pastoris
      with emphasis on the lipids which form the matrix of this compartment.
      Prerequisite for this effort was the design of a standardized and reliable
      isolation protocol of the plasma membrane at high purity. Analysis of isolated
      plasma membrane samples from P. pastoris revealed an increase of
      phosphatidylserine and a decrease of phosphatidylcholine compared to bulk
      membranes. The amount of saturated fatty acids in the plasma membrane was higher
      than in total cell extracts. Ergosterol, the final product of the yeast sterol
      biosynthetic pathway, was found to be enriched in plasma membrane fractions,
      although markedly lower than in Saccharomyces cerevisiae. A further
      characteristic feature of the plasma membrane from P. pastoris was the enrichment
      of inositol phosphorylceramides over neutral sphingolipids, which accumulated in
      internal membranes. The detailed analysis of the P. pastoris plasma membrane is
      discussed in the light of cell biological features of this microorganism
      especially as a microbial cell factory for heterologous protein production. 

PMID- 24680653
TI  - Sticholysin I-membrane interaction: an interplay between the presence of
      sphingomyelin and membrane fluidity.
AB  - Sticholysin I (St I) is a pore-forming toxin (PFT) produced by the Caribbean Sea
      anemone Stichodactyla helianthus belonging to the actinoporin protein family, a
      unique class of eukaryotic PFT exclusively found in sea anemones. As for
      actinoporins, it has been proposed that the presence of sphingomyelin (SM) and
      the coexistence of lipid phases increase binding to the target membrane. However,
      little is known about the role of membrane structure and dynamics (phase state,
      fluidity, presence of lipid domains) on actinoporins' activity or which regions
      of the membrane are the most favorable platforms for protein insertion. To gain
      insight into the role of SM on the interaction of St I to lipid membranes we
      studied their binding to monolayers of phosphatidylcholine (PC) and SM in
      different proportions. Additionally, the effect of acyl chain length and
      unsaturation, two features related to membrane fluidity, was evaluated on St I
      binding to monolayers. This study revealed that St I binds and penetrates
      preferentially and with a faster kinetic to liquid-expanded films with high
      lateral mobility and moderately enriched in SM. A high content of SM induces a
      lower lateral diffusion and/or liquid-condensed phases, which hinder St I binding
      and penetration to the lipid monolayer. Furthermore, the presence of lipid domain
      borders does not appear as an important factor for St I binding to the lipid
      monolayer. 

PMID- 24680654
TI  - Membrane binding of human phospholipid scramblase 1 cytoplasmic domain.
AB  - Human phospholipid scramblase 1 (SCR) consists of a large cytoplasmic domain and
      a small presumed transmembrane domain near the C-terminal end of the protein.
      Previous studies with the SCRDelta mutant lacking the C-terminal portion (last 28
      aa) revealed the importance of this C-terminal moiety for protein function and
      calcium-binding affinity. The present contribution is intended to elucidate the
      effect of the transmembrane domain suppression on SCRDelta binding to model
      membranes (lipid monolayers and bilayers) and on SCRDelta reconstitution in
      proteoliposomes. In all cases the protein cytoplasmic domain showed a great
      affinity for lipid membranes, and behaved in most aspects as an intrinsic
      membrane protein. Assays have been performed in the presence of
      phosphatidylserine, presumably important for the SCR cytoplasmic domain to be
      electrostatically anchored to the plasma membrane inner surface. The fusion
      protein maltose binding protein-SCR has also been studied as an intermediate case
      of a molecule that can insert into the bilayer hydrophobic core, yet it is stable
      in detergent-free buffers. Although the intracellular location of SCR has been
      the object of debate, the present data support the view of SCR as an integral
      membrane protein, in which not only the transmembrane domain but also the
      cytoplasmic moiety play a role in membrane docking of the protein. 

PMID- 24680656
TI  - Transcription analysis of the response of chicken bursa of Fabricius to avian
      leukosis virus subgroup J strain JS09GY3.
AB  - BACKGROUND: Avian leukosis virus subgroup J (ALV-J) causes tumours and
      immunosuppression in chickens. The host-ALV interactions at the transcriptional
      level are unknown. In this study, gene expression profiling was performed to
      analyse the bursa response induced by ALV-J strain JS09GY3 in chickens. RESULTS:
      A total of 594 gene transcripts displaying differential expression during ALV-J
      infection were identified. These differentially expressed genes are involved in
      binding, biological regulation, metabolic processes (MYF6 and FABP3), response to
      stimulus (F13A1 and CNGA3) and immune system processes (LY86, CATHL2, CCL4, and
      OASL), and several differentially expressed genes (e.g., ETV7, MMP9, and NOV) are
      involved in tumourigenesis. Eight differentially expressed genes were confirmed
      by quantitative reverse transcription-PCR (qRT-PCR). Based on pathway analysis,
      the notable signalling pathways mainly included cytokine-cytokine receptor
      interaction, the JAK-STAT signalling pathway and the RIG-1-like receptor
      signalling pathway. CONCLUSIONS: The gene expression profile obtained in this
      study may aid a better understanding of the molecular pathogenesis of ALV-J
      infection in chickens.

PMID- 24680655
TI  - EmrE dimerization depends on membrane environment.
AB  - The small multi-drug resistant (SMR) transporter EmrE functions as a homodimer.
      Although the small size of EmrE would seem to make it an ideal model system, it
      can also make it challenging to work with. As a result, a great deal of
      controversy has surrounded even such basic questions as the oligomeric state.
      Here we show that the purified protein is a homodimer in isotropic bicelles with
      a monomer-dimer equilibrium constant (KMD(2D)) of 0.002-0.009mol% for both the
      substrate-free and substrate-bound states. Thus, the dimer is stabilized in
      bicelles relative to detergent micelles where the KMD(2D) is only 0.8-0.95mol%
      (Butler et al. 2004). In dilauroylphosphatidylcholine (DLPC) liposomes KMD(2D) is
      0.0005-0.0008mol% based on Forster resonance energy transfer (FRET) measurements,
      slightly tighter than bicelles. These results emphasize the importance of the
      lipid membrane in influencing dimer affinity. 

PMID- 24680658
TI  - Is regular depilation really necessary after a pilonidal sinus excision?

PMID- 24680657
TI  - Grass carp reovirus induces apoptosis and oxidative stress in grass carp
      (Ctenopharyngodon idellus) kidney cell line.
AB  - Grass carp hemorrhage is an acute contagious disease caused by grass carp
      reovirus (GCRV). The pathogenesis of GCRV and the relationship between GCRV and
      the host cells remain unclear. The aim of the present study was to investigate
      the relations among apoptosis, intracellular oxidative stress and virus
      replication in GCRV infected-cells. The results showed that GCRV induced
      activation of caspase proteases as early as 12 h, and reached maximum activities
      at 24 h or 48 h post-infection in a grass carp kidney cell line (CIK cells).
      Meanwhile, the levels of tumor necrosis factor (TNF-alpha) and interleukin-1beta
      (IL-1beta) also were increased in GCRV-infected CIK cells and showed a
      statistically significant difference from 24 h to 96 h post-infection. The
      infection of GCRV caused the destruction of entire monolayer and the death of
      host cells. Accompanied by the infection, a severe oxidative stress occurred,
      which led to extensive loss of antioxidants and formation of lipid peroxidation
      after 48 h post-infection. These data suggested that the apoptosis which was
      triggered at an early stage (12-24 h) in the viral infection cycle, might be
      independent of virus replication, while the oxidative stress induced by GCRV was
      mostly related to the virus replication.

PMID- 24680659
TI  - Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of
      metalloproteinases-2 ratio as a predictor of disease progression in patients with
      metastatic renal cell carcinoma receiving sunitinib.
AB  - OBJECTIVES: To assess the significance of circulating matrix metalloproteinases
      (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as predictors of
      disease progression in patients with metastatic renal cell carcinoma (mRCC)
      receiving sunitinib. MATERIALS AND METHODS: Circulating levels of MMP-2, MMP-9,
      TIMP-1, and TIMP-2 in sera from 52 patients with mRCC treated with sunitinib were
      measured at the baseline and on the first day of each treatment cycle until
      progression using enzyme-linked immunosorbent assays. RESULTS: The baseline level
      of MMP-9 in nonresponders to sunitinib was significantly higher than that in
      responders, whereas the baseline level of TIMP-2 in nonresponders was
      significantly lower than that in responders. However, there were no significant
      differences in the serum levels of MMP-2 and TIMP-1 between responders and
      nonresponders. The serum MMP-9/TIMP-2 ratio at the baseline in nonresponders was
      also significantly higher than that in responders. Univariate analysis showed
      that the MMP-9/TIMP-2 ratio, but not MMP-9 and TIMP-2 levels, was significantly
      correlated with progression-free survival, and the MMP-9/TIMP-2 ratio, in
      addition to the Memorial Sloan-Kettering Cancer Center classification and C
      reactive protein level, appeared to be independently associated with progression
      free survival on multivariate analysis. Furthermore, despite the lack of
      significant differences in the serum levels of MMP-9 and TIMP-2 between the
      baseline and the time of progression, the MMP-9/TIMP-2 ratio at the time of
      progression was significantly elevated compared with the baseline ratio.
      CONCLUSIONS: An imbalance between the serum MMP-9 and TIMP-2 levels could be a
      novel biomarker to predict disease progression in patients with mRCC under
      treatment with sunitinib.

PMID- 24680660
TI  - Precystectomy serum levels of carbohydrate antigen 19-9, carbohydrate antigen
      125, and carcinoembryonic antigen: prognostic value in invasive urothelial
      carcinoma of the bladder.
AB  - OBJECTIVES: To evaluate the prognostic value of precystectomy carbohydrate
      antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), and carcinoembryonic
      antigen (CEA) levels in invasive urothelial carcinoma of the bladder (UCB).
      METHODS AND MATERIALS: Preoperatively collected serum samples from patients with
      invasive UCB who underwent radical cystectomy between 2004 and 2009 were used to
      measure CA 19-9, CA 125, and CEA levels. Laboratory cutoff points were used to
      define elevated marker levels (CA 19-9>37 U/ml, CA 125>35 U/ml, and CEA>3.8
      U/ml). The Cox regression model was used to identify independent predictors of
      recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 186
      patients with the mean age of 69 years (range: 36-89) and median follow-up of 4
      years (range: 0.1-7.2) were included in the study. Overall, 94 (51%) patients had
      pathologic organ-confined disease (<=T2) and 92 (49%) had pathologic locally
      advanced UCB (pT3-T4 or positive lymph node or both). The mean CA 19-9, CA 125,
      and CEA levels were 11.6 U/ml (range:<0.6-111), 11.5 U/ml (range: 3-56), and 2.2
      ng/ml (range: 0.3-30.2), respectively. Levels of CA 19-9, CEA, and CA 125 were
      elevated in 7 (3%), 25 (13%), and 3 (1%) patients, respectively. Median 3-year
      RFS and OS were 72%. Using the multivariate Cox regression model, elevated levels
      of CA 19-9 and CEA were found to be independent predictors of worse 3-year OS
      (hazard ratio [HR] = 2.7, P = 0.05 and HR = 2, P = 0.03, respectively), and an
      elevated level of CA 19-9 was an independent predictor of worse 3-year RFS (HR =
      2.8, P = 0.05). Precystectomy CA 125 level was not associated with oncological
      outcome. CONCLUSIONS: Elevated precystectomy serum levels of CA 19-9 and CEA are
      independent predictors of worse oncological outcome in patients with invasive
      UCB. Further studies are needed to elucidate the role of these markers in the
      management of UCB.

PMID- 24680661
TI  - Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for
      the functional regeneration of injured rat uterus.
AB  - Serious injuries of endometrium in women of reproductive age are often followed
      by uterine scar formation and a lack of functional endometrium predisposing to
      infertility or miscarriage. Bone marrow-derived mesenchymal stem cells (BM-MSCs)
      have shown great promise in clinical applications. In the present study, BM-MSCs
      loaded onto degradable collagen membranes were constructed. Collagen membranes
      provided 3-dimmensional architecture for the attachment, growth and migration of
      rat BM-MSCs and did not impair the expression of the stemness genes. We then
      investigated the effect of collagen/BM-MSCs constructs in the healing of severe
      uterine injury in rats (partial full thickness uterine excision). At four weeks
      after the transplantation of collagen/BM-MSCs constructs, BM-MSCs were mainly
      located to the basal membrane of regenerative endometrium. The wounded tissue
      adjacent to collagen/BM-MSCs constructs expressed higher level of bFGF, IGF-1,
      TGFbeta1 and VEGF than the corresponding tissue in rats receiving collagen
      construct alone or in spontaneous regeneration group. Moreover, the collagen/BM
      MSCs system increased proliferative abilities of uterine endometrial and muscular
      cells, facilitated microvasculature regeneration, and restored the ability of
      endometrium to receive the embryo and support its development to a viable stage.
      Our findings indicate that BM-MSCs may support uterine tissue regeneration. 

PMID- 24680662
TI  - Coassembly of amphiphilic peptide EAK16-II with histidinylated analogues and
      implications for functionalization of beta-sheet fibrils in vivo.
AB  - EAK16-II (AEAEAKAKAEAEAKAK) is one of the first building blocks of
      environmentally responsive materials. This self-assembling peptide undergoes
      solution-to-gel transition when transferred from a low to high ionic strength
      environment. Previously we have demonstrated the histidinylated analogue EAKIIH6
      (AEAEAKAKAEAEAKAKHHHHHH) coassembles with the parent peptide to render His-tags
      as a functionalization mechanism in vitro and in vivo. The present study aimed to
      understand the pathways by which the analogue coassembles with EAK16-II. The
      results presented herein suggested two competing but not mutually exclusive
      events in the coassembly. Atomic force microscopic and gel electrophoretic data
      showed that EAKIIH6 self-sorted to high molecular weight species without EAK16
      II. Self-sorting of EAKIIH6 was inhibited by the parent peptide in a
      concentration dependent manner. Injecting mixtures containing EAKIIH6
      subcutaneously rendered His-tags detectable in live mice for at least 312 h,
      despite diluting the histidinylated analogue by 10-50 folds compared to a
      previous formulation. The study provided a formulation by which in vivo display
      of His-tags was attained without excess amphiphilic peptides. By increasing
      coassembling efficiency, the likelihood of generating immunogenic aggregates
      outside the main fibrils could be minimized. These findings provide insights for
      rational functionalization of in situ self-gelling materials.

PMID- 24680663
TI  - Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and Synergistic
      Targeted therapy of residual tumor during HIFU ablation.
AB  - High intensity focused ultrasound (HIFU) has attracted the great attention in
      tumor ablation due to its non-invasive, efficient and economic features. However,
      HIFU ablation has its intrinsic limitations for removing the residual tumor
      cells, thus the tumor recurrence and metastasis cannot be avoided in this case.
      Herein, we developed a multifunctional targeted poly(lactic-co-glycolic acid)
      (PLGA) nanobubbles (NBs), which not only function as an efficient ultrasound
      contrast agent for tumor imaging, but also a targeted anticancer drug carrier and
      excellent synergistic agent for enhancing the therapeutic efficiency of HIFU
      ablation. Methotrexate (MTX)-loaded NBs were synthesized and filled with
      perfluorocarbon gas subsequently using a facile but general double emulsion
      evaporation method. The active tumor-targeting monoclonal anti-HLA-G antibodies
      (mAbHLA-G) were further conjugated onto the surface of nanobubbles. The mAbHLA
      G/MTX/PLGA NBs could enhance the ultrasound imaging both in vitro and in vivo,
      and the targeting efficiency to HLA-G overexpressing JEG-3 cells has been
      demonstrated. The elaborately designed mAbHLA-G/MTX/PLGA NBs can specifically
      target to the tumor cells both in vitro and in vivo, and their blood circulation
      time in vivo was much longer than non-targeted MTX/PLGA NBs. Further therapeutic
      evaluations showed that the targeted NBs as a synergistic agent can significantly
      improve the efficiency of HIFU ablation by changing the acoustic environment, and
      the focused ultrasound can promote the on-demand MTX release both in vitro and in
      vivo. The in vivo histopathology test and immunohistochemical analysis showed
      that the mAbHLA-G/MTX/PLGA NBs plus HIFU group presented most serious coagulative
      necrosis, the lowest proliferation index and the highest apoptotic index.
      Therefore, the successful introduction of targeted mAbHLA-G/MTX/PLGA NBs provides
      an excellent platform for the highly efficient, imaging-guided and non-invasive
      HIFU synergistic therapy of cancer with the supplementary functions of killing
      residual tumor cells and preventing tumor recurrence/metastasis.

PMID- 24680664
TI  - Identification of tomoregulin-1 as a novel addicsin-associated factor.
AB  - Addicsin is a novel factor encoding a 23-kDa hydrophobic protein that is highly
      upregulated in the amygdala nuclei of morphine-administered mice. It is a murine
      homolog of human JWA and rat glutamate transporter-associated protein 3-18
      (GTRAP3-18), a negative modulator of the neural glutamate transporter excitatory
      amino acid carrier 1 (EAAC1). Recent findings demonstrated that addicsin
      participates in various physiological processes by forming hetero- or
      homomultimeric complexes. However, the binding targets and molecular functions of
      addicsin remain largely unknown. To identify potential factors that associate
      with mouse addicsin, we performed a yeast two-hybrid screen using a 17-day-old
      mouse whole embryo cDNA library. We identified tomoregulin-1 (TR1) as a novel
      addicsin-associated factor. TR1, a type I transmembrane protein containing two
      follistatin-like modules and an epidermal growth factor-like domain, participates
      in nodal and bone morphogenetic protein signaling. Immunoprecipitation assays
      demonstrated that TR1 bound to addicsin, and that amino acids 145-188 of addicsin
      and amino acids 228-266 of TR1 were important for the formation of the addicsin
      TR1 heterocomplex. The double-fluorescent immunohistochemical analysis revealed
      that addicsin and TR1 were coexpressed in neurons in the mature mouse brain
      regions tested. Moreover, TR1 showed a punctuate pattern throughout the cell,
      with preferential expression on the cell surface when expressed alone. However,
      TR1 predominantly redistributed to the endoplasmic reticulum (ER) when
      coexpressed with addicsin. Furthermore, coexpression of an addicsin mutant that
      lacked TR1 binding ability had little effect on the distribution of TR1.
      Biotinylation assays showed that coexpression of addicsin with TR1 suppressed the
      cell surface expression of TR1. Wound-healing assays demonstrated that the
      interaction of addicsin with TR1 had a significant effect on cell migration.
      These findings demonstrate that addicsin in the ER controls intracellular TR1
      trafficking from the ER to plasma membrane and regulates cell migration through
      its interaction with TR1.

PMID- 24680666
TI  - Assessing behavioral control across reinforcer solutions on a fixed-ratio
      schedule of reinforcement in rats.
AB  - Instrumental behavior can shift from flexible, goal-directed actions to
      automatic, stimulus-response actions. The satiety-specific devaluation test
      assesses behavioral flexibility by evaluating reward seeking after temporary
      devaluation of the reinforcer via satiety; a decrease in responding compared to
      control conditions indicates goal-directed behavior. We have observed variability
      in the outcome of this test that may be dependent on the reinforcer. Another test
      of habit, contingency degradation, involves changing the action-outcome
      association over the course of retraining and determines whether reward seeking
      is sensitive to changing contingencies. We hypothesized that the outcome of the
      contingency-degradation test would remain consistent across reinforcers, while
      the satiety-specific devaluation test may vary across reinforcers because it
      depends on the ability of the reinforcer to induce satiety. Therefore, we trained
      rats to self-administer 1.5% sucrose, 10% sucrose, 10% ethanol, or 10 mM
      monosodium glutamate (MSG) on a fixed-ratio (FR5) schedule that has been shown to
      promote long-term, goal-directed responding. Next, behavioral flexibility was
      evaluated in three satiety-specific devaluation tests over 6 weeks. Finally, we
      investigated reward seeking after contingency-degradation training. All groups
      displayed sensitivity to satiety-specific devaluation in the first test,
      indicating goal-directed behavior. While the 10% sucrose and ethanol groups
      remained goal-directed, the 1.5% sucrose and MSG groups exhibited habit-like
      behavior in later tests. Nevertheless, all groups displayed decreased responding
      in an extinction session after contingency-degradation training, indicating goal
      directed behavior. These results demonstrate that tests of behavioral flexibility
      can yield dissimilar results in the same rats. Next, rats from the 1.5% sucrose
      group underwent the entire experiment again, now self-administering 10% sucrose.
      These rats showed pronounced goal-directed behavior in satiety-specific and
      contingency-degradation tests under 10% sucrose conditions, further suggesting
      that the reinforcer solution affected the outcome of the satiety-specific
      devaluation test. We conclude that reinforcer characteristics should be
      considered when investigating habit-like behavior in alcohol research. 

PMID- 24680665
TI  - Applications of schedule-induced polydipsia in rodents for the study of an
      excessive ethanol intake phenotype.
AB  - Schedule-induced polydipsia (SIP) is generated by subjecting a highly motivated
      animal to a sub-optimal rate of food reinforcement while also providing access to
      a fluid. SIP is one of several adjunctive (or displacement) behaviors that are
      expressed in an exaggerated form that is deemed 'excessive.' This feature makes
      SIP an attractive model for studying an excessive ethanol drinking phenotype in
      rodents. Multiple experimental variables are crucial for the full manifestation
      of adjunctive drinking, including the degree of food deprivation, the inter
      pellet interval selected, and the size of the food reward offered. Although these
      variables were extensively studied and optimized for water polydipsia in rats, a
      similarly customized approach to ethanol SIP and application of the procedure in
      mice have largely been curtailed in favor of the default variable values
      historically used for water SIP in rats. Further, ethanol SIP also requires
      careful consideration of variables such as taste and ethanol concentration.
      Investigation of the stress axis and neurochemical systems such as dopamine and
      serotonin in mediating adjunctive drinking stemmed from two leading hypotheses
      regarding the underlying mechanisms of SIP generation: 1) SIP as a coping
      strategy to mitigate stress associated with the aversive environmental condition,
      and 2) SIP as a displacement of reward in a highly motivated animal. Ethanol SIP
      is a powerful model of excessive intake because it can generate an ethanol
      dependent state and sustain frequent and intoxicating levels of blood ethanol
      with voluntary oral consumption. The required food deprivation and the loss of
      the excessive drinking phenotype following removal of the generator schedule are
      the two main limitations of the model. Future utility of ethanol SIP will be
      enhanced by more fully dissecting the underlying hormonal and neurochemical
      mechanisms and optimizing experimental variables for ethanol SIP on a per species
      and strain basis. 

PMID- 24680667
TI  - A new fibrinogen-related protein from Argopecten irradians (AiFREP-2) with broad
      recognition spectrum and bacteria agglutination activity.
AB  - Fibrinogen-related proteins (FREPs) are a kind of pattern recognition receptors
      (PRRs) containing fibrinogen-like (FBG) domains, and they play curial roles in
      the innate immune response. In the present study, a new FREP protein was
      identified from bay scallop Argopecten irradians (designated as AiFREP-2). The
      full-length cDNA of AiFREP-2 was of 1299 bp with an open reading frame of 762 bp
      encoding a polypeptide of 253 amino acids, including a signal sequence and an FBG
      domain. The FBG domain in AiFREP-2 was highly similar to those of ficolins,
      tenascins and other FREPs. The mRNA expression of AiFREP-2 could be detected in
      all the examined tissues with the highest level in gill. The mRNA expression of
      AiFREP-2 in hemocytes was significantly up-regulated post the stimulation of
      lipopolysaccharide (LPS), peptidoglycan (PGN) and beta-glucan (GLU) (P < 0.01).
      The recombinant AiFREP-2 (rAiFREP-2) could bind not only different PAMP ligands
      including LPS, PGN and GLU, but also various microbes including Gram-negative
      bacteria (Vibrio anguillarum), Gram-positive bacteria (Staphylococcus aureus) and
      fungus (Pichia pastoris and Yarrowia lipolytica). Additionally, rAiFREP-2
      exhibited obvious agglutination activity towards Gram-negative bacteria V.
      anguillarum and Gram positive bacteria S. aureus. The results indicated that
      AiFREP-2 was involved in the immune response against Gram-negative bacteria, Gram
      positive bacteria and fungus as a PRR in bay scallop, and the information was
      helpful to understand the innate immune defense mechanisms of mollusks.

PMID- 24680669
TI  - Lidocaine effect on flotillin-2 distribution in detergent-resistant membranes of
      equine jejunal smooth muscle in vitro.
AB  - Lidocaine is the most commonly chosen prokinetic for treating postoperative ileus
      in horses, a motility disorder associated with ischaemia-reperfusion injury of
      intestinal tissues. Despite the frequent use of lidocaine, the mechanism
      underlying its prokinetic effects is still unclear. Previous studies suggested
      that lidocaine altered cell membrane characteristics of smooth muscle cells.
      Therefore, the present study aimed to elucidate effects of lidocaine
      administration on characteristics of detergent-resistant membranes in equine
      jejunal smooth muscle. Lidocaine administration caused significant redistribution
      of flotillin-2, a protein marker of detergent-resistant membranes, in fractions
      of sucrose-density-gradients obtained from ischaemia-reperfusion injured smooth
      muscle solubilised with Triton X-100. It was concluded that lidocaine induced
      disruption of detergent-resistant membranes which might affect ion channel
      activity and therefore enhance smooth muscle contractility. 

PMID- 24680668
TI  - A non-active-site SET domain surface crucial for the interaction of MLL1 and the
      RbBP5/Ash2L heterodimer within MLL family core complexes.
AB  - The mixed lineage leukemia-1 (MLL1) enzyme is a histone H3 lysine 4 (H3K4)
      monomethyltransferase and has served as a paradigm for understanding the
      mechanism of action of the human SET1 family of enzymes that include MLL1-MLL4
      and SETd1a,b. Dimethylation of H3K4 requires a sub-complex including WRAD (WDR5,
      RbBP5, Ash2L, and DPY-30), which binds to each SET1 family member forming a
      minimal core complex that is required for multiple lysine methylation. We
      recently demonstrated that WRAD is a novel histone methyltransferase that
      preferentially catalyzes H3K4 dimethylation in a manner that is dependent on an
      unknown non-active-site surface from the MLL1 SET domain. Recent genome
      sequencing studies have identified a number of human disease-associated missense
      mutations that localize to the SET domains of several MLL family members. In this
      investigation, we mapped many of these mutations onto the three-dimensional
      structure of the SET domain and noticed that a subset of MLL2 (KMT2D, ALR, MLL4)
      associated Kabuki syndrome missense mutations map to a common solvent-exposed
      surface that is not expected to alter enzymatic activity. We introduced these
      mutations into the MLL1 SET domain and observed that all are defective for H3K4
      dimethylation by the MLL1 core complex, which is associated with a loss of the
      ability of MLL1 to interact with WRAD or with the RbBP5/Ash2L heterodimer. Our
      results suggest that amino acids from this surface, which we term the Kabuki
      interaction surface or KIS, are required for formation of a second active site
      within SET1 family core complexes. 

PMID- 24680670
TI  - Characterization of the oral microbiota of healthy cats using next-generation
      sequencing.
AB  - The healthy feline oral cavity harbours a rich assemblage of microorganisms,
      which have not previously been well characterized using modern sequencing
      technology. The goal of this study was to accurately describe the oral microbiota
      of 11 healthy cats using next-generation sequencing. Sequencing generated a total
      of 10,177 operational taxonomic units, representing 273 genera from 18 bacterial
      phyla. Eight bacterial phyla made up 97.6% of sequences: Proteobacteria (75.2%),
      Bacteroidetes (9.3%), Firmicutes (6.7%), SR1 (2.7%), Spirochaetes (1.8%),
      Fusobacteria (1.3%), and Actinobacteria (0.6%). The most prevalent genus-level
      phylotypes were: an unclassified Pasteurellaceae (18.7%), Moraxella (10.9%),
      Thermomonas (6.9%), an unclassified Comamonadaceae (5.6%), Neisseria (4.9%), an
      unclassified Moraxellaceae (4.4%), and Pasteurella (4.3%). Results suggest that
      the feline oral microbiota are largely conserved between cats at the phylum
      level, and that the population is highly diverse, rich and even. A strong core
      microbiome was evident among all cats, yet significant differences in oral
      bacterial populations were observed across cats in each household.

PMID- 24680671
TI  - Effect of fatty acid composition of the sow diet on the innate and adaptive
      immunity of the piglets after weaning.
AB  - This study investigated whether the immunocompetence of piglets at weaning was
      modulated by including different sources of n-3 polyunsaturated fatty acids
      (PUFA) in the maternal diet. From day 73 of gestation until weaning at 4 weeks,
      32 pregnant sows were fed a palm oil-based diet (control group) or a diet
      including 1% linseed oil (C18:3n-3), 1% echium oil (C18:3n-3, C18:4n-3, C18:3n-6)
      or 1% fish oil (C20:5n-3, C22:6n-3). It was hypothesized that each diet would
      differently affect immune function through effects such as specific eicosanoid
      production. Piglets were fed a conventional diet without added n-3 PUFA from
      weaning until day 35 post-weaning. At weaning and 21 days post-weaning, four
      piglets per litter were immunized with bovine thyroglobulin. Blood samples were
      taken from weaning until day 35 post-weaning to determine thyroglobulin-specific
      antibodies, serum amyloid A (SAA) concentration and fatty acid composition. The
      fatty acid composition of the maternal diets was reflected in the plasma and red
      blood cells of the weaned piglets. The onset of the thyroglobulin-specific IgM
      response differed between dietary groups, with a delay in response for piglets
      from sows fed the fish oil diet. No significant dietary effects were observed on
      the thyroglobulin-specific IgG and IgA titres or on SAA concentrations in the
      piglet serum. Including n-3 PUFA in the maternal diet at the concentrations used
      in the present study had no major effects on the adaptive and innate immunity of
      the piglets after weaning.

PMID- 24680672
TI  - Efficacy of a control program for bovine trichomonosis based on testing and
      culling infected bulls in beef cattle managed under mountain pastoral systems of
      Northern Spain.
AB  - Bovine trichomonosis (BT) is a sexually transmitted disease that is considered a
      cause of early reproductive failure in cattle under extensive management
      conditions. Recently, Tritrichomonas foetus was detected in 41.5% of herds from
      one representative beef cattle breed (Asturiana de la Montana; AM) reared in
      traditional mountain systems in Spain. The objective of the present study was to
      evaluate the effect of BT on reproductive performance and the economic
      consequences in AM herds. The benefits of a control program based on testing and
      culling infected bulls were also studied by comparing T. foetus prevalence and
      reproductive data before and after the implementation of the control measures. In
      infected herds, T. foetus infection increased calving intervals by 79 days
      (P<0.0001) and resulted in a higher percentage of cows-not-in calf (36% vs. 19%;
      P<0.001). An economic analysis showed that BT could reduce income by 68.7% in AM
      herds. The implementation of the control program decreased calving intervals
      (P<0.0001) and increased calving percentage (P<0.05). T. foetus prevalence showed
      a significant decline compared with the prevalence before implementing the
      control program (P<0.05). Nevertheless, after 2 years, the herd prevalence did
      not decrease (12.7-13.6%; P>0.05) and the herd incidence was 22.72%. The testing
      and culling policy was effective in improving reproductive efficiency but the
      complete elimination of BT without substantial changes in management appears
      unlikely because putative risk factors associated with the disease are present in
      the management of this breed.

PMID- 24680673
TI  - Using the Microsoft Kinect to measure breast volume: thoughts and experiences.

PMID- 24680674
TI  - What is left behind when the lights go off? Comparing the abundance and
      composition of litter in urban areas with different intensity of nightlife use in
      Mar del Plata, Argentina.
AB  - Nightlife activities represents an important source of urban litter; the latter
      often being left behind or abandoned in public places and streets. Mar del Plata
      is a very important city on the Atlantic coast of Argentina and is the main
      tourism destination in the South Atlantic region of South America. However, few
      studies on urban litter related to nightlife activities have been conducted in
      the area. Here we assessed (i) the abundance and composition of litter, and (ii)
      the spatial and temporal variations of its abundance, diversity, richness and
      evenness in urbanized areas with different intensity of nightlife activities from
      April 2008 to March 2009. An overall of 13,503 items were counted. Around 92% of
      the total litter was comprised by cigarette butts, papers and plastics. We found
      significant spatial differences in the abundance of litter between sampling
      sites, with the greatest amounts of litter at the Alem site followed by the
      Hipolito site (both with an intensive nightlife activity) compared with the
      Chauvin site (a quiet high-income neighborhood). The composition of litter of the
      Alem and the Hipolito sites was relatively similar and both sites differ with
      respect to the Chauvin site. Cigarette butts, papers, and plastics were the items
      that contributed most to the dissimilarity between sampling sites. The diversity
      of litter was the single community parameter that significantly differed from the
      other seasons. We discussed the potential effect of nightlife activities on the
      amounts and quality of urban litter in the city of Mar del Plata. 

PMID- 24680675
TI  - Pharmacological modulation of abnormal involuntary DOI-induced head twitch
      response in male DBA/2J mice: I. Effects of D2/D3 and D2 dopamine receptor
      selective compounds.
AB  - Because of the complexity and heterogeneity of human neuropsychiatric disorders,
      it has been difficult to identify animal models that mimic the symptoms of these
      neuropathologies and can be used to screen for antipsychotic agents. For this
      study we selected the murine 5HT2A/2C receptor agonist-induced head twitch
      response (HTR) induced by the administration of 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI), which has been proposed as an animal model of symptoms
      associated with a variety of behavioral and psychiatric conditions. We
      investigated the DOI-induced HTR in male DBA/2J mice using a panel of D2-like
      (D2, D3 and D4) and D2 dopamine receptor selective compounds. When DBA/2J mice
      were administered a daily dose of DOI (5 mg/kg), tolerance to the DOI occurs.
      However, administrations of the same dose of DOI every other day (48 h) or on a
      weekly basis did not lead to tolerance and the ability to induce tolerance after
      daily administration of DOI remains intact after repeated weekly administration
      of DOI. Subsequently, a panel of D2-like dopamine receptor antagonists was found
      to effectively inhibit the DOI-induced HTR in DBA/2J mice. However, the benzamide
      eticlopride, which is a high affinity D2-like antagonist, was a notable
      exception. SV 293, SV-III-130s and N-methylbenperidol, which exhibit a high
      affinity for D2 versus the D3 dopamine receptor subtypes (60- to 100-fold binding
      selectivity), were also found to inhibit the HTR in DBA/2J mice. This observation
      suggests a functional interaction between dopaminergic and serotonergic systems
      through D2 dopamine receptors and the 5-HT2A serotonin receptors in vivo. 

PMID- 24680676
TI  - Two essential peritrophic matrix proteins mediate matrix barrier functions in the
      insect midgut.
AB  - The peritrophic matrix (PM) in the midgut of insects consists primarily of chitin
      and proteins and is thought to support digestion and provide protection from
      abrasive food particles and enteric pathogens. We examined the physiological
      roles of 11 putative peritrophic matrix protein (PMP) genes of the red flour
      beetle, Tribolium castaneum (TcPMPs). TcPMP genes are differentially expressed
      along the length of the midgut epithelium of feeding larvae. RNAi of individual
      PMP genes revealed no abnormal developmental phenotypes for 9 of the 11 TcPMPs.
      However, RNAi for two PMP genes, TcPMP3 and TcPMP5-B, resulted in depletion of
      the fat body, growth arrest, molting defects and mortality. In situ permeability
      assays after oral administration of different-sized FITC-dextran beads
      demonstrated that the exclusion size of the larval peritrophic matrix (PM)
      decreases progressively from >2 MDa to <4 kDa from the anterior to the most
      posterior regions of the midgut. In the median midguts of control larvae, 2 MDa
      dextrans were completely retained within the PM lumen, whereas after RNAi for
      TcPMP3 and TcPMP5-B, these dextrans penetrated the epithelium of the median
      midgut, indicating loss of structural integrity and barrier function of the
      larval PM. In contrast, RNAi for TcPMP5-B, but not RNAi for TcPMP3, resulted in
      breakdown of impermeability to 4 and 40 kDa dextrans in the PM of the posterior
      midgut. These results suggest that specific PMPs are involved in the regulation
      of PM permeability, and that a gradient of barrier function is essential for
      survival and fat body maintenance.

PMID- 24680678
TI  - Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing
      apoptosis.
AB  - Mesenchymal stem cells (MSCs) have generated a great deal of interest in the
      field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known
      to exhibit extensive proliferation potential and can undergo multilineage
      differentiation, sharing similar characteristics to bone marrow-derived MSCs.
      However, as the effect of AdSCs on tumor growth has not been studied
      sufficiently, we assessed the degree to which AdSCs affect the proliferation of
      prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the
      proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3)
      human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in
      fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced
      apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling
      pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both
      LNCaP and PC3 cells was related to the TGF-beta signaling pathway. Consistent
      with our in vitro observations, local transplantation of AdSCs delayed the growth
      of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice.
      This is the first preclinical study to have directly demonstrated that AdSC
      induced PCa cell apoptosis may occur via the TGF-beta signaling pathway,
      irrespective of androgen-responsiveness. Since autologous AdSCs can be easily
      isolated from adipose tissue without any ethical concerns, we suggest that
      therapy with these cells could be a novel approach for patients with PCa. 

PMID- 24680677
TI  - Transient increase in proteinuria, poly-ubiquitylated proteins and ER stress
      markers in podocyte-specific autophagy-deficient mice following unilateral
      nephrectomy.
AB  - Previous studies have revealed that podocytes normally can be associated with a
      very high degree of autophagic activity, and that a lack of autophagic activity
      in podocytes is associated with susceptibility to disease and to late-onset
      glomerulosclerosis. In the present study, we conducted unilateral nephrectomy as
      a surgical model for acute nephron reduction. First, using GFP-LC3 transgenic
      mice to monitor autophagy, we found that glomerular autophagy could be
      transiently suppressed by surgery, but that it was restored quickly. To further
      explore the significance of podocyte autophagy after unilateral nephrectomy, we
      investigated podocyte-specific Atg7-deficient mice. The knockout mice exhibited
      no pathological phenotype compared with wild-type mice before nephrectomy.
      However, 1 day after nephrectomy, significantly higher levels of proteinuria and
      ultrastructural changes that included foot process effacement and a significant
      reduction in podocyte number were detected in mice harboring Atg7-deficient
      podocytes. Moreover, biochemical and immunohistochemical analyses showed a robust
      increase in polyubiquitin levels and ER stress markers in the glomeruli of the
      mice with autophagy-deficient podocytes. These results show the importance of the
      autophagic process in podocytes for maintaining a normal degree of filtration
      function during the adaptation to compensatory kidney hypertrophy following
      unilateral nephrectomy.

PMID- 24680679
TI  - Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte
      apoptosis in metabolic syndrome.
AB  - Metabolic syndrome is a major risk factor for cardiovascular diseases, and
      increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after
      myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor,
      is involved in such various cellular events as apoptosis, proliferation, and
      glucose and lipid metabolism in several cell types. Apoptosis is positively
      correlated with mitochondrial translocation of Nur77 in the cancer cells.
      However, the roles of Nur77 on cardiac myocytes in patients with metabolic
      syndrome remain unclear. The objective of this study was to determine whether
      Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome
      after I/R injury, and, if so, to identify the underlying molecular mechanisms
      responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome
      models. In this report, we observed that, accompanied by the substantial decline
      in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as
      cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes
      cultured in a high-glucose and high-fat medium, we found that excessive H2O2 led
      to the significant alteration in mitochondrial membrane potential and
      translocation of Nur77 from the nucleus to the mitochondria. However, inhibition
      of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes
      in membrane potential mediated by H2O2 and reduced myocardial cell injury.
      Therefore, these data provide a potential underlying mechanism for cardiac
      dysfunction in metabolic syndrome and the suppression of Nur77 translocation may
      provide an effective approach to reduce cardiac injury in the process. 

PMID- 24680680
TI  - Adiponutrin: a multimeric plasma protein.
AB  - The interest in adiponutrin stems from adiponutrin variant I148M, which is
      strongly associated to non-alcoholic fatty liver disease. Adiponutrin has to date
      been considered to be solely an intracellular protein, with a role in lipid
      metabolism in liver and adipose tissue. However, a physiologically relevant role
      for adiponutrin has not been found. The aim of this study was to investigate the
      presence of adiponutrin in human plasma, a new facet of adiponutrin research. We
      demonstrate that adiponutrin is present in plasma as disulfide-bond dependent
      multimers, estimated to circulate at a concentration of 1.25-4 nM. Experiments
      reveal that adiponutrin is released from HepG2 cells in the presence of oleate.
      The presence of adiponutrin in plasma makes it accessible for clinical
      investigations and use as a potential biomarker for metabolic disease.

PMID- 24680681
TI  - The expression of miR-21 and miR-375 predict prognosis of esophageal cancer.
AB  - BACKGROUND: MicroRNA is a class of small, well-conserved, non-coding RNAs, and
      could play a potential role as diagnostic and prognostic biomarkers of esophageal
      cancers. We aimed to review comprehensively the evidence of microRNA as
      prognostic biomarkers in esophageal cancers. METHODS: Studies were identified by
      searching PubMed, Embase and Web of Science until November 2013. Descriptive
      characteristics of studies were described and an additional meta-analysis for
      specific microRNAs which were studied most frequently was performed. Pooled
      hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were
      calculated. Fixed model or random model method was chosen depending on the
      heterogeneity among the studies. RESULTS: Twenty-two studies including a total of
      1946 participants were enrolled after a strict filtering and qualifying process.
      Among 33 prognostic microRNAs identified for esophageal cancer, miR-21 and miR
      375 appeared more frequently. The median study size was 70.5 patients (29-249
      patients) and the median HR was 3.305 (IQR=1.615-7.31). For the studies
      evaluating miR-21's association with overall survival (OS), the pooled HR
      suggested that high level of miR-21 has a negative impact on OS (HR=1.52[1.17
      1.98], P=0.001). As for miR-375, the pooled HR for OS (high/low) was 0.53 (95%
      CI: 0.39-0.73, P<0.001), indicated that low level of miR-375 has a negative
      impact on OS. These results indicated that microRNAs show promising associations
      with prognosis in esophageal cancer. Up-regulation of miR-21 and down-regulation
      of miR-375 can predict unfavourable prognosis in esophageal cancer.

PMID- 24680682
TI  - Early senescence in heterozygous ABCA1 mutation skin fibroblasts: a gene dosage
      effect beyond HDL deficiency?
AB  - PURPOSE: Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects
      reported in heterozygous state regard plasma HDL, cell cholesterol efflux and
      coronary artery disease. We investigated whether in vitro replicative skin
      fibroblast senescence shown in TD proband (Hom), his father (Het), and in a
      healthy control might be induced in a "gene-dosage way". METHODS: Senescence was
      evaluated by staining test for beta-Galactosidase and telomere length (TL) on
      fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density
      lipoprotein receptor) gene expression was also evaluated. RESULTS: Hom cells
      showed early senescent morphology and reduced growth at all passages in vitro.
      The cell positive percentage for beta-Galactosidase test was highly increased in
      Hom compared to Het cells at late replicative status (66.1% vs 41.3%
      respectively). TL was significantly shorter at high stage either in Hom
      (p<0.0001) or in Het (p<0.005). At early replication cycles ABCG1 gene expression
      was about 3-fold higher in Hom compared to Het cells (0.44 vs 0.14 arbitrary
      unit). CONCLUSIONS: ABCA1 gene mutation may have "gene-dosage way" effect on in
      vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene
      expression could highlight a role of ABCA1 on cytoskeleton regulation associated
      to cell cholesterol metabolism.

PMID- 24680683
TI  - RPS27a promotes proliferation, regulates cell cycle progression and inhibits
      apoptosis of leukemia cells.
AB  - Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides
      imparting a role in ribosome biogenesis and post-translational modifications of
      proteins. The high expression level of RPS27a was reported in solid tumors, and
      we found that the expression level of RPS27a was up-regulated in advanced-phase
      chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study,
      we explored the function of RPS27a in leukemia cells by using CML cell line K562
      cells and its imatinib resistant cell line K562/G01 cells. It was observed that
      the expression level of RPS27a was high in K562 cells and even higher in K562/G01
      cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and
      K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and
      G2/M phases and increased cell apoptosis induced by imatinib. Combination of
      shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase
      3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p
      ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown
      cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle
      progression and inhibits apoptosis of leukemia cells. It appears that drugs
      targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a
      novel therapy strategy in TKI resistant CML patients. 

PMID- 24680684
TI  - Impaired motor coordination in Pitx3 overexpression mice.
AB  - Midbrain dopaminergic (DA) neurons are involved in the regulation of voluntary
      movement and in emotion-related behaviors and are affected in Parkinson's disease
      (PD). The homeodomain transcription factor Pitx3, which is uniquely expressed in
      midbrain DA neurons, plays a critical role in the development, function and
      maintenance of midbrain DA neurons. Pitx3 deficiency results in selective
      deficits of midbrain DA neurons in the substantia nigra pars compacta (SNc),
      reminiscent of the specific DA neuronal loss observed in PD. In this study, we
      found that selective overexpression of Pitx3 in intact midbrain DA neurons
      significantly affects the function of midbrain DA neurons. We observed changes in
      DA levels and gene expressions in mice overexpressing Pitx3. Furthermore, motor
      coordination and locomotion activities are significantly affected in mice
      overexpressing Pitx3, suggesting that the expression level of Pitx3 plays an
      important role in the function of midbrain DA neuron in vivo. 

PMID- 24680685
TI  - Emodin-mediated cross-linking enhancement for extracellular matrix homeostasis.
AB  - The extracellular matrix (ECM) is an essential element of mammalian organisms,
      and its cross-linking formation plays a vital role in ECM development and
      postnatal homeostasis. Defects in cross-link formation caused by aging, genetic,
      or environmental factors are known to cause numerous diseases in mammals. To
      augment the cross-linking formation of ECM, the present study established a
      ZsGreen reporter system controlled by the promoter of lysyl oxidase-like 1 gene
      (LOXL1), which serves as both a scaffold element and a cross-linking enzyme in
      the ECM. By using this system in a drug screen, we identified emodin as a strong
      enhancer of LOXL1 expression that promoted cross-linking formation of ECM in all
      the tested systems, including human fibroblast cells, cultured human skin
      tissues, and animals that received long-term emodin treatment. Collectively, the
      results suggest that emodin may serve as an effective drug or supplement for ECM
      homeostasis. 

PMID- 24680686
TI  - The TWEAK-Fn14 dyad is involved in age-associated pathological changes in
      skeletal muscle.
AB  - Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major
      clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its
      receptor Fn14 were identified as key mediators of muscle wasting in various
      catabolic states. However, the role of the TWEAK-Fn14 pathway in pathological
      changes in skeletal muscle during aging remains unknown. In this study, we
      demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month
      old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly
      increased the levels of specific muscle proteins and blunted the age-associated
      fiber atrophy in mice. While gene expression of two prominent muscle-specific E3
      ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated
      proteins and the expression of autophagy-related molecule Atg12 were
      significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice
      during aging. Ablation of Fn14 significantly diminished the DNA-binding activity
      of transcription factor nuclear factor-kappa B (NF-kappaB), gene expression of
      various inflammatory molecules, and interstitial fibrosis in skeletal muscle of
      aged mice. Collectively, our study suggests that the TWEAK-Fn14 signaling axis
      contributes to age-associated muscle atrophy and fibrosis potentially through its
      local activation of proteolytic systems and inflammatory pathways. 

PMID- 24680687
TI  - Cleavable carbamate linkers for controlled protein delivery from hydrogels.
AB  - The reversible attachment of proteins to polymers is one potential strategy to
      control protein release from hydrogels. In this study, we report the reversible
      attachment of lysozyme to poly(ethylene glycol) (PEG) by degradable carbamate
      linkers. Phenyl groups with different substituents were used to control the rate
      of carbamate hydrolysis and the resulting protein release. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis showed modification with 1-3 PEG chains per
      lysozyme molecule. Protein PEGylation and PEG chain elimination occurred without
      changes in secondary protein structure, as demonstrated by circular dichroism
      spectroscopy. The lytic activity of lysozyme was restored to 73.4+/-1.7%-92.5+/
      1.2% during PEG chain elimination. Attached PEG chains were eliminated within 24h
      to 28days, depending on the used linker molecule. When formulated into hydrogels,
      a maximum of about 60% of the initial dose was released within 7days to 21days.
      Linker elimination occurs 'traceless', so that the protein is released in its
      native, unmodified form. Altogether, we believe that tethering proteins by
      degradable carbamate linkers is a promising strategy to control their release
      from hydrogels. 

PMID- 24680689
TI  - The impact of time to surgery on outcomes in patients with traumatic brain
      injury: a literature review.
AB  - AIM: To review the relationship between the time interval to surgery and outcomes
      in patients with traumatic brain injury (TBI). METHODS: A literature review was
      conducted by employing several search strategies, including electronic database
      searches and footnote chasing. The quality of the selected studies was assessed
      in terms of internal and external validity. Data regarding authors, publication
      year, sample size, surgical procedure, time interval to surgery, and outcome was
      extracted. RESULTS: Among 16 finally selected studies, five studies (31.3%) found
      that patient outcome was significantly affected by the timing of surgery and 11
      (68.7%) did not. The impact of time to surgery on outcomes was not significant in
      most (75%) of the studies targeting patients with severe TBI. The effect of time
      to surgery on outcome showed different findings depending on the type of surgical
      procedure. A significant effect of time to surgery on outcome was reported in one
      (14.2%) of the seven studies targeting patients who underwent haematoma
      evacuation and in four (44.4%) of the nine studies on patients who underwent
      decompressive craniectomy. CONCLUSION: This review shows that current opinion is
      still divided regarding when to operate. Despite this discrepancy, most authors
      agree that the timing of decompression is crucial to outcome.

PMID- 24680688
TI  - Phosphorylation of syntaxin 3B by CaMKII regulates the formation of t-SNARE
      complexes.
AB  - Ribbon synapses in the retina lack the t-SNARE (target-soluble N-ethylmaleimide
      sensitive factor attachment protein receptor) syntaxin 1A that is found in
      conventional synapses of the nervous system, but instead contain the related
      isoform syntaxin 3B. Previous studies have demonstrated that syntaxin 3B is
      essential for synaptic vesicle exocytosis in ribbon synapses, but syntaxin 3B is
      less efficient than syntaxin 1A in binding the t-SNARE protein SNAP-25 and
      catalyzing vesicle fusion. We demonstrate here that syntaxin 3B is localized
      mainly on the presynaptic membrane of retinal ribbon synapses and that a subset
      of syntaxin 3B is localized in close proximity to the synaptic ribbon. We show
      further, that syntaxin 3B can be phosphorylated by the Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII). We determine that the phosphorylation site
      is located close to the N-terminus at T14. Syntaxin 3B with a phosphomimetic
      mutation (T14E) had a stronger binding affinity for SNAP-25 compared with wild
      type syntaxin 3B. We propose that phosphorylation of syntaxin 3B by CaMKII can
      modulate the assembly of the SNARE complex in ribbon synapses of the retina, and
      might regulate the exocytosis of synaptic vesicles in ribbon synapses. 

PMID- 24680690
TI  - Isoquercitrin: pharmacology, toxicology, and metabolism.
AB  - The flavonoid isoquercitrin (quercetin-3-O-beta-d-glucopyranoside) is commonly
      found in medicinal herbs, fruits, vegetables and plant-derived foods and
      beverages. This article reviews the occurrence, preparation, bioavailability,
      pharmacokinetics, toxicology and biological activity of isoquercitrin and
      "enzymatically modified (alpha-glucosylated) isoquercitrin" (EMIQ). Pure
      isoquercitrin can now be obtained on a large scale by enzymatic rutin hydrolysis
      with alpha-l-rhamnosidase. Isoquercitrin has higher bioavailability than
      quercetin and displays a number of chemoprotective effects both in vitro and in
      vivo, against oxidative stress, cancer, cardiovascular disorders, diabetes and
      allergic reactions. Although small amounts of intact isoquercitrin can be found
      in plasma and tissues after oral application, it is extensively metabolized in
      the intestine and the liver. Biotransformation of isoquercitrin includes
      deglycosylation, followed by formation of conjugated and methylated derivatives
      of quercetin or degradation to phenolic acids and carbon dioxide. The acceptable
      daily intake of (95%) isoquercitrin and of EMIQ was estimated to be 5.4 and
      4.9mg/kg/day, respectively. Adverse effects of higher doses in rats included
      mostly (benign) chromaturia; nevertheless some drug interactions may occur due to
      the modulation of the activity and/or expression of drug
      metabolizing/transporting systems. With respect to the safety, affordability and
      beneficial pharmacological activities, highly pure isoquercitrin is a prospective
      substance for food supplementation. 

PMID- 24680691
TI  - The effects of bioactive compounds from plant foods on mitochondrial function: a
      focus on apoptotic mechanisms.
AB  - Mitochondria are essential organelles for cellular integrity and functionality
      maintenance and their imparement is implicated in the development of a wide range
      of diseases, including metabolic, cardiovascular, degenerative and
      hyperproliferative pathologies. The identification of different compounds able to
      interact with mitochondria for therapeutic purposes is currently becoming of
      primary importance. Indeed, it is well known that foods, particularly those of
      vegetable origin, present several constituents with beneficial effects on health.
      This review summarizes and updates the most recent findings concerning the
      mechanisms through which different dietary compounds from plant foods affect
      mitochondria functionality in healthy and pathological in vitro and in vivo
      models, paying particular attention to the pathways involved in mitochondrial
      biogenesis and apoptosis. 

PMID- 24680693
TI  - Cotton proteomics for deciphering the mechanism of environment stress response
      and fiber development.
AB  - Cotton fiber is considered as the backbone of the textile industry. The
      productivity of cotton crop is severely hampered by the occurrence of pathogens,
      pests, and various environmental factors. Nevertheless, cotton plant has
      developed sophisticated mechanisms to respond to environment stresses to avoid
      detrimental effects on its growth and development. Therefore, understanding the
      mechanisms of cotton fiber development and environment stress response is of
      considerable interest for designing agriculture breeding strategies to ensure
      sustainable productivity. The application of proteomics technologies to advance
      our knowledge in cotton fiber development and abiotic/biotic stress tolerance has
      increased dramatically in the last 5years as evidenced by the large amount of
      publications in this area. This review summarizes the work which has been
      reported for cotton proteomics and evaluates the findings in context of the
      approaches that are widely employed with the aim to generate novel insight useful
      for cotton improvement. BIOLOGICAL SIGNIFICANCE: Cotton (Gossypium spp.) is
      considered as the foremost commercially important fiber crop grown all over the
      world and is deemed as the backbone of the textile industry. Cotton is also an
      important source of edible oil seed and a nutrient-rich food crop as cottonseed
      contains high-quality protein and oil. The growth and productivity of cotton crop
      are often hampered by various biotic stress factors, such as insect pests and
      pathogens. In addition, cotton plants are frequently subjected to unavoidable
      environmental factors that cause abiotic stress, such as salt, heat and drought.
      Proteomic techniques provide one of the best options for understanding the gene
      function and phenotypic changes during cotton fiber development and stress
      response. This review first summarizes the work which has been reported for
      cotton proteomics about cotton fiber development and abiotic/biotic stress
      tolerance, and also evaluates the findings in context of the approaches that are
      widely employed during last 5years, with the aim to generate novel insight useful
      for cotton improvement. This article is part of a Special Issue entitled:
      Proteomics of non-model organisms.

PMID- 24680692
TI  - Damaging and protective bystander cross-talk between human lung cancer and normal
      cells after proton microbeam irradiation.
AB  - Most of the studies of radiation-induced bystander effects (RIBE) have been
      focused on understanding the radiobiological changes observed in bystander cells
      in response to the signals from irradiated cells in a normal cell population with
      implications to radiation risk assessment. However, reports on RIBE with
      relevance to cancer radiotherapy especially investigating the bidirectional and
      criss-cross bystander communications between cancer and normal cells are limited.
      Hence, in present study employing co-culture approach, we have investigated the
      bystander cross-talk between lung cancer (A549) and normal (WI38) cells after
      proton-microbeam irradiation using gamma-H2AX foci fluorescence as a measure of
      DNA double-strand breaks (DSBs). We observed that in A549-A549 co-cultures,
      irradiated A549 cells exert damaging effects in bystander A549 cells, which were
      found to be mediated through gap junctional intercellular communication (GJIC).
      However, in A549-WI38 co-cultures, irradiated A549 did not affect bystander WI38
      cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue
      effect) in irradiated A549 cells, which was independent of GJIC. On the other
      hand, in response to irradiated WI38 cells neither of the bystander cells (A549
      or WI38) showed significant increase in gamma-H2AX foci. The observed bystander
      signalling between tumour and normal cells may have potential implications in
      therapeutic outcome of cancer radiotherapy. 

PMID- 24680694
TI  - Decreased expression of phosphorylated placental heat shock protein 27 in human
      and ovine intrauterine growth restriction (IUGR).
AB  - INTRODUCTION: Intrauterine growth restriction (IUGR) has been documented to
      increase placental apoptosis at term. HSP27 has been shown to be involved in the
      control of apoptosis. Our objective is to determine the expression of
      phosphorylated HSP27 (p-HSP27) in human IUGR, and to determine the role of HSP27
      during gestation in an ovine hyperthermia induced model of IUGR. METHODS: Human
      placenta tissue samples were collected at term to quantify p-HSP27. Pregnant
      sheep were placed in hyperthermic (HT) conditions to induce IUGR. Placental
      tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days
      gestational age (dGA) to determined phosphorylated and total HSP27 across the
      development of IUGR. RESULTS: Phosphorylated HSP27 was significantly reduced in
      human placenta IUGR compared to controls at term. HSP27 was increased throughout
      gestation during the development of IUGR in the sheep. P-HSP27 was increased in
      early gestation (55 dGA), and decreased near term (130 dGA). The near term
      decrease was localized to the trophoblast cells of the placenta. DISCUSSION AND
      CONCLUSION: We conclude that decreased p-HSP27 at term is present when placental
      apoptosis is increased during IUGR. This could be a factor leading to the
      decreased placental weight observed during IUGR.

PMID- 24680695
TI  - Progesterone receptor membrane component 1 (PGRMC1) expression in fetal membranes
      among women with preterm premature rupture of the membranes (PPROM).
AB  - PGRMC1 function is implicated in maintaining fetal membrane (FM) integrity.
      PGRMC1 was detectable primarily in the cytoplasm of FM cells and was actively
      regulated in FMs and relevant for PGRMC1-mediated progesterone action. By cell
      type, PGRMC1 expression was higher in amnion and chorion compared with decidua.
      By clinical phenotype, PGRMC1 expression was higher among preterm-no-labor and
      term-no-labor subjects compared to PPROM. PGRMC1 expression appears to be
      diminished in PPROM subjects.

PMID- 24680696
TI  - Opportunities and challenges in development of phosphoantigens as Vgamma9Vdelta2
      T cell agonists.
AB  - In contrast to T cells that express the more prevalent alphabeta T cell receptor
      and respond to peptide antigens, T cells that express the Vgamma9Vdelta2 T cell
      receptor detect and respond to non-peptide phosphorous-containing small molecules
      known as phosphoantigens. Because gammadelta T cells are early responders to
      infections and malignancies, it has been suggested that stimulation of their
      activity with small molecule phosphoantigen drugs may hold promise for
      therapeutic interventions. Recent studies have greatly advanced our knowledge of
      phosphoantigens as well as their cellular receptors. At the same time, clinical
      trials of phosphoantigens have suggested that development of these Vgamma9Vdelta2
      T cell agonists has met unexpected challenges. In this commentary, we summarize
      the biology that underlies phosphoantigen activity and discuss the structural
      features of synthetic phosphoantigens that affect both their ability to stimulate
      Vgamma9Vdelta2 T cells and their potential as therapeutic agents. 

PMID- 24680697
TI  - A simple TALEN-based protocol for efficient genome-editing in Drosophila.
AB  - Drosophila is a well-established genetic model organism: thousands of point
      mutations, deficiencies or transposon insertions are available from stock
      centres. However, to date, it is still difficult to modify a specific gene locus
      in a defined manner. A potential solution is the application of transcription
      activator-like effector nucleases (TALENs), which have been used successfully to
      mutate genes in various model organisms. TALENs are constructed by fusion of TALE
      proteins to the endonuclease FokI, resulting in artificial, sequence-specific
      endonucleases. They induce double strand breaks, which are either repaired by
      error-prone non-homologous end joining (NHEJ) or homology directed repair (HDR).
      We developed a simple TALEN-based protocol to mutate any gene of interest in
      Drosophila within approximately 2 months. We inject mRNA coding for two TALEN
      pairs targeting the same gene into embryos, employ T7 endonuclease I screening of
      pooled F1 flies to identify mutations and generate a stable mutant stock in the
      F3 generation. We illustrate the efficacy of our strategy by mutating CG11617, a
      previously uncharacterized putative transcription factor with an unknown function
      in Drosophila. This demonstrates that TALENs are a reliable and efficient
      strategy to mutate any gene of interest in Drosophila.

PMID- 24680698
TI  - TALEN utilization in rice genome modifications.
AB  - Transcription activator-like effector nucleases (TALENs), the newly developed and
      powerful genetic tools for precise genome editing, are fusion proteins of TAL
      effectors as DNA binding domains and the cleavage domain of FokI endonuclease. As
      a pair, the central repeat regions of TALENs determine the DNA binding
      specificity for the two sub-target sites; and the dimeric non-specific FokI
      cleavage domains cause a DNA double strand break (DSB) between the bound
      sequences. In vivo, cells repair the DSBs through either non-homologous end
      joining (NHEJ) pathway or homologous recombination (HR) pathway. Various methods
      have been developed for easy and fast assembly of TALEN genes for their
      utilization in a variety of eukaryotic cells or organisms. Here we present a
      TALEN-based rice genome modification protocol including constructing modularly
      assembled TALENs, rice transformation, and mutant screening. 

PMID- 24680700
TI  - Exploiting ChEMBL database to identify indole analogs as HCV replication
      inhibitors.
AB  - Molecular docking, 3D-QSAR CoMSIA and similarity search were combined in a multi
      step framework with the ultimate goal to identify potent indole analogs, in the
      ChEMBL database, as inhibitors of HCV replication. The crystal structure of HCV
      RNA-dependent RNA polymerase (NS5B GT1b) was utilized and 41 known inhibitors
      were docked into the enzyme "Palm II" active site. In a second step, the docking
      pose of each compound was used in a receptor-based alignment for the generation
      of the CoMSIA fields. A validated 3D-QSAR CoMSIA model was subsequently built to
      accurately estimate the activity values. The proposed framework gives insight
      into the structural characteristics that affect the binding and the inhibitory
      activity of these analogs on HCV polymerase. The obtained in silico model was
      used to predict the activity of novel compounds prior to their synthesis and
      biological testing, within a Virtual Screening framework. The ChEMBL database was
      mined to afford compounds containing the indole scaffold that are predicted to
      possess high activity and thus can be prioritized for biological screening. 

PMID- 24680699
TI  - Strategies for exploring TGF-beta signaling in Drosophila.
AB  - The TGF-beta pathway is an evolutionarily conserved signal transduction module
      that mediates diverse biological processes in animals. In Drosophila, both the
      BMP and Activin branches are required for viability. Studies rooted in classical
      and molecular genetic approaches continue to uncover new developmental roles for
      TGF-beta signaling. We present an overview of the secreted ligands, transmembrane
      receptors and cellular Smad transducer proteins that compose the core pathway in
      Drosophila. An assortment of tools have been developed to conduct tissue-specific
      loss- and gain-of-function experiments for these pathway components. We discuss
      the deployment of these reagents, with an emphasis on appropriate usage and
      limitations of the available tools. Throughout, we note reagents that are in need
      of further improvement or development, and signaling features requiring further
      study. A general theme is that comparison of phenotypes for ligands, receptors,
      and Smads can be used to map tissue interactions, and to separate canonical and
      non-canonical signaling activities. Core TGF-beta signaling components are
      subject to multiple layers of regulation, and are coupled to context-specific
      inputs and outputs. In addition to fleshing out how TGF-beta signaling serves the
      fruit fly, we anticipate that future studies will uncover new regulatory nodes
      and modes and will continue to advance paradigms for how TGF-beta signaling
      regulates general developmental processes. 

PMID- 24680702
TI  - Whole-mount immunostaining of the adult Drosophila gastrointestinal tract.
AB  - The gastrointestinal (GI) tract harbors an essential barrier epithelium that
      separates an organism from its changing external environment. As such, the gut
      epithelium is a fascinating nexus of stem cell biology, immunology and
      physiology. Investigators have sought to mine this rich interface for new
      biological and mechanistic insights. Many of the powerful genetic approaches
      developed in Drosophila have proven effective in the study of the gut. The goal
      of this article is to present a method for dissecting, immunostaining and
      mounting samples of the adult Drosophila GI tract. This protocol combines readily
      with techniques to label cell lineages and/or challenge the system with
      environmental perturbations, which are briefly discussed. 

PMID- 24680703
TI  - Characterization of a stearoyl-acyl carrier protein desaturase gene from
      potential biofuel plant, Pongamia pinnata L.
AB  - A new full length cDNA clone encoding stearoyl-ACP desaturase (SAD) was isolated
      from seeds of Pongamia pinnata, an oil yielding legume plant. The cDNA clone
      (PpSAD) contained a single open reading frame of 1182-bp coding for 393 amino
      acids with a predicted molecular mass of 45.04 kDa, and shares similarity with
      SAD from other plants. Characteristics of the deduced protein were predicted and
      analyzed using molecular homology modeling; its three dimensional structure
      strongly resembled the crystal structure of Ricinus communis (RcSAD). Southern
      blot analysis indicated that 'sad' is a multiple copy gene and was a member of a
      small gene family. Expression analysis using quantitative real-time PCR revealed
      that the gene showed marked distinct expression during different stages of seed
      developments. The results of the expression analysis in this study, combined with
      existing research, suggest that 'sad' gene may be involved in the regulation of
      plant seed growth and development.

PMID- 24680701
TI  - Methods for studying planar cell polarity.
AB  - Planar cell polarity (PCP) is the polarity of epithelial cells in the plane
      orthogonal to the apical-basal axis, and is controlled by a partially defined
      signaling system. PCP related signaling also plays roles in cell migration,
      tissue re-organization and stem cell differentiation during embryonic
      development, and later, in regeneration and repair. Aberrant signaling has been
      linked to a broad range of pathophysiologies including cancer, developmental
      defects, and neurological disorders. The deepest mechanistic insights have come
      from studies of PCP in Drosophila. In this chapter we review tools and methods to
      study PCP signaling in Drosophila epithelia, where it was found to involve
      asymmetric protein localization that is coordinated between adjacent cells. Such
      signaling has been most extensively studied in wing, eye, and abdomen, but also
      in other tissues such as leg and notum. In the adult fly, PCP is manifested in
      the coordinated direction of hairs and bristles, as well as the organization of
      ommatidia in the eye. The polarity of these structures is preceded by asymmetric
      localization of PCP signaling proteins at the apical junctions of epithelial
      cells. Based on genetic and molecular criteria, the proteins that govern PCP can
      be divided into distinct modules, including the core module, the
      Fat/Dachsous/Four-jointed (Fat/Ds/Fj) module (often referred to as the 'global'
      module) as well as tissue specific effector modules. Different tissues and tissue
      regions differ in their sensitivity to disturbances in the various modules of the
      PCP signaling system, leading to controversies about the interactions among the
      modules, and emphasizing the value of studying PCP in multiple contexts. Here, we
      review methods including those generally applicable, as well as some that are
      selectively useful for analyses of PCP in eye (including eye discs), wing
      (including wing discs), pupal and adult abdomen, and the cuticle of larvae and
      embryos.

PMID- 24680704
TI  - A novel mechanism for activation of Aurora-A kinase by Ajuba.
AB  - Aurora-A is a centrosome-localized serine/threonine kinase, which plays a
      critical role in mitotic and meiotic cell division processes. However, the
      regulation of Aurora-A is still not fully understood. Previously, we have found
      an intramolecular inhibitory regulation mechanism of Aurora-A: the N-terminal
      regulatory domain (aa 1-128, Nt) can interact with the C-terminal catalytic
      domain (aa 129-403, Cd) and inhibit the kinase activity of Aurora-A. In this
      study, we found that the PreLIM domain of Ajuba, another important activator of
      Aurora-A, induces the autophosphorylation of the C-terminal kinase domain of
      Aurora-A, and is phosphorylated by the C-terminal. Moreover, the LIM domain of
      Ajuba can competitively bind to the N-terminal of Aurora-A, and inhibited the
      interaction between N-terminal and C-terminal of Aurora A. Taken together, these
      results suggest a novel mechanism for regulation of Aurora-A by Ajuba. 

PMID- 24680705
TI  - Down-regulation of miR-199b associated with imatinib drug resistance in 9q34.1
      deleted BCR/ABL positive CML patients.
AB  - Chronic myeloid leukemia (CML) occurs due to t(9,22) (q34;q11) and molecularly
      BCR/ABL gene fusion. About 15-18% Philadelphia positive CML patients have gene
      deletions around the translocation breakpoints on 9q34.1. The microRNAs (miRNAs),
      namely miR-219-2 and miR-199b, centromeric to the ABL1 gene are frequently lost
      in CML patients. We have designed a study to determine miR-219-2 and miR-199b
      expression levels which would help to understand the prognosis of imatinib
      therapy. A total of 150 CML patients were analyzed to identify 9q deletion.
      Fluorescent in-situ hybridization (FISH) was performed using BCR/ABL dual color,
      dual fusion probe to study the signal pattern and BAC probes for miR-199b and miR
      219-2 (RP11-339B21 and RP11-395P17) to study the miRNA deletions. The expression
      level of miRNA was analyzed by real-time polymerase chain reaction (RT-PCR). FISH
      analysis revealed 9q34.1 deletion in 34 (23%) CML patients. The deletions were
      not detected using BAC probes for miRNAs in 9q deleted patients. The expression
      analysis showed down-regulation of miR-199b and miR-219-2 in the 9q deleted
      patients (34 CML) as compared to a pool of patients without deletion. However,
      miR-199b (9q34.11) was significantly (p=0.001) down-regulated compared to miR-219
      2. The follow-up study showed that the miR-199b was found to be strongly
      associated with imatinib resistance, as 44.11% patients showed resistance to
      imatinib therapy. Hence, the deletion in 9q34.1 region (ABL) plays an important
      role in disease pathogenesis. Eventually, miRNAs can provide new therapeutic
      strategies and can be used as a prognostic indicator.

PMID- 24680706
TI  - Editorial overview: emerging viruses.

PMID- 24680707
TI  - Monte Carlo simulations of enzymatic reactions in crowded media. Effect of the
      enzyme-obstacle relative size.
AB  - We perform Monte Carlo simulations in three-dimensional (3D) lattice in order to
      study diffusion-controlled and mixed activation-diffusion reactions following an
      irreversible Michaelis-Menten scheme in crowded media. The simulation data reveal
      the rate coefficient dependence on time for diffusion-controlled bimolecular
      reactions developing in three-dimensional media with obstacles, as predicted by
      fractal kinetics approach. For the cases of mixed activation-diffusion reactions,
      the fractality of the reaction decreases as the activation control increases. We
      propose a modified form of the Zipf-Mandelbrot equation to describe the time
      dependence of the rate coefficient, k(t)=k0(1+t/tau)(-)(h). This equation
      provides a good description of the fractal regime and it may be split into two
      terms: one that corresponds to the initial rate constant (k0) and the other one
      correlated with the kinetics fractality. Additionally, the proposed equation
      contains and links two limit expressions corresponding to short and large periods
      of time: k1=k0 (for t?tau) that relates to classical kinetics and the well-known
      Kopelman's equation k~t(-)(h) (for t?tau) associated to fractal kinetics. The tau
      parameter has the meaning of a crossover time between these two limiting
      behaviours. The value of k0 is mainly dependent on the excluded volume and the
      enzyme-obstacle relative size. This dependence can be explained in terms of the
      radius of an average confined volume that every enzyme molecule feels, and
      correlates very well with the crossover length obtained in previous studies of
      enzyme diffusion in crowding media. 

PMID- 24680708
TI  - Ultrasound induced cancer immunotherapy.
AB  - Recently, the use of ultrasound (US) has been shown to have potential in cancer
      immunotherapy. High intensity focused US destruction of tumors may lead to
      immunity forming in situ in the body by immune cells being exposed to the tumor
      debris and immune stimulatory substances that are present in the tumor remains.
      Another way of achieving anti-cancer immune responses is by using US in
      combination with microbubbles and nanobubbles to deliver genes and antigens into
      cells. US leads to bubble destruction and the forces released to direct delivery
      of the substances into the cytoplasm of the cells thus circumventing the natural
      barriers. In this way tumor antigens and antigen-encoding genes can be delivered
      to immune cells and immune response stimulating genes can be delivered to cancer
      cells thus enhancing immune responses. Combination of bubbles with cell-targeting
      ligands and US provides an even more sophisticated delivery system whereby the
      therapy is not only site specific but also cell specific. In this review we
      describe how US has been used to achieve immunity and discuss the potential and
      possible obstacles in future development. 

PMID- 24680709
TI  - Imperatorin induces Mcl-1 degradation to cooperatively trigger Bax translocation
      and Bak activation to suppress drug-resistant human hepatoma.
AB  - Imperatorin is a small molecule nature compound isolated from the root of
      Angelica dahurica, and has been shown to exhibit multiple bioeffector functions,
      including anti-cancer activity. However, the molecular mechanism underlying
      imperatorin in suppression of tumor growth is unknown. In this study, we aimed at
      elucidating the molecular mechanisms underlying imperatorin function and
      determining the efficacy of imperatorin in suppression of drug-resistant human
      liver cancer. We observed that imperatorin suppresses tumor cell growth through
      inducing apoptosis, and imperatorin is more effective in induction of multidrug
      resistant human liver cancer cells in vitro. We further determined that
      imperatorin induces apoptosis through both extrinsic and intrinsic apoptosis
      pathway. At the molecular level, we identified Mcl-1 as the molecular target of
      imperatorin and determined that imperatorin induces proteosome-dependent Mcl-1
      degradation to release Bak and Bax to trigger apoptosis in liver cancer cells.
      Consistent with its in vitro apoptosis induction activity, imperatorin exhibited
      potent activity against multidrug-resistant liver cancer xenograft growth in
      vivo. Taken together, we determined that imperatorin is a Mcl-1 degradation
      inducer that can effectively suppress multidrug-resistant human liver cancer
      growth in vivo, and thus holds great promise for development as an effective
      small molecule anti-cancer agent in human liver cancer therapy to overcome drug
      resistance.

PMID- 24680710
TI  - Featuring the special issue guest editor: Dan Peer, Ph.D.

PMID- 24680711
TI  - Adaptive smoothing of multi-shell diffusion weighted magnetic resonance data by
      msPOAS.
AB  - We present a novel multi-shell position-orientation adaptive smoothing (msPOAS)
      method for diffusion weighted magnetic resonance data. Smoothing in voxel and
      diffusion gradient space is embedded in an iterative adaptive multiscale
      approach. The adaptive character avoids blurring of the inherent structures and
      preserves discontinuities. The simultaneous treatment of all q-shells improves
      the stability compared to single-shell approaches such as the original POAS
      method. The msPOAS implementation simplifies and speeds up calculations, compared
      to POAS, facilitating its practical application. Simulations and heuristics
      support the face validity of the technique and its rigorousness. The
      characteristics of msPOAS were evaluated on single and multi-shell diffusion data
      of the human brain. Significant reduction in noise while preserving the fine
      structure was demonstrated for diffusion weighted images, standard DTI analysis
      and advanced diffusion models such as NODDI. MsPOAS effectively improves the poor
      signal-to-noise ratio in highly diffusion weighted multi-shell diffusion data,
      which is required by recent advanced diffusion micro-structure models. We
      demonstrate the superiority of the new method compared to other advanced
      denoising methods. 

PMID- 24680712
TI  - Gray matter volume is associated with rate of subsequent skill learning after a
      long term training intervention.
AB  - The ability to predict learning performance from brain imaging data has
      implications for selecting individuals for training or rehabilitation
      interventions. Here, we used structural MRI to test whether baseline variations
      in gray matter (GM) volume correlated with subsequent performance after a long
      term training of a complex whole-body task. 44 naive participants were scanned
      before undertaking daily juggling practice for 6weeks, following either a high
      intensity or a low intensity training regime. To assess performance across the
      training period participants' practice sessions were filmed. Greater GM volume in
      medial occipito-parietal areas at baseline correlated with steeper learning
      slopes. We also tested whether practice time or performance outcomes modulated
      the degree of structural brain change detected between the baseline scan and
      additional scans performed immediately after training and following a further
      4weeks without training. Participants with better performance had higher
      increases in GM volume during the period following training (i.e., between scans
      2 and 3) in dorsal parietal cortex and M1. When contrasting brain changes between
      the practice intensity groups, we did not find any straightforward effects of
      practice time though practice modulated the relationship between performance and
      GM volume change in dorsolateral prefrontal cortex. These results suggest that
      practice time and performance modulate the degree of structural brain change
      evoked by long-term training regimes. 

PMID- 24680713
TI  - Enhancing the management response to oil spills in the Tuscany Archipelago
      through operational modelling.
AB  - A new approach towards the management of oil pollution accidents in marine
      sensitive areas is presented in this work. A set of nested models in a
      downscaling philosophy was implemented, externally forced by existing regional
      operational products. The 3D hydrodynamics, turbulence and the oil
      transport/weathering models are all linked in the same system, sharing the same
      code, exchanging information in real time and improving its ability to correctly
      reproduce the spill. A wind-generated wave model is also implemented using the
      same downscaling philosophy. Observations from several sources validated the
      numerical components of the system. The results obtained highlight the good
      performance of the system and its ability to be applied for oil spill forecasts
      in the region. The success of the methodology described in this paper was
      underline during the Costa Concordia accident, where a high resolution domain was
      rapidly created and deployed inside the system covering the accident site. 

PMID- 24680714
TI  - Trace elements in tissues of cetacean species rarely stranded along the Israeli
      Mediterranean coast.
AB  - In this paper we present the concentrations of Hg, Cd, Se, Pb, Cu, Mn, Zn and Fe
      in organs of 6 non-common specimens of cetaceans that were stranded along the
      Israeli Mediterranean coast (IMC), during 2002-2010: two fin whales, one minke
      whale, one Cuvier's beaked whale, one rough-toothed dolphin, and one Risso's
      dolphin. Most of the specimens were calves stranded by accident. Concentrations
      of Hg and Cd were low in tissues of the baleen whales and higher in the toothed
      whales, with maximum concentrations of 1067 mg kg(-1) Hg in the liver of the
      Risso's dolphin and 29 mg kg(-1) Cd in the kidney of the Cuvier's beaked whale.
      As far as we are aware, this is the first report of trace elements in baleen
      whales in the Eastern Mediterranean, and the first report of trace elements in
      minke whale and rough-toothed dolphin in the Mediterranean.

PMID- 24680715
TI  - Comparisons of the metabolic responses of two subtidal nassariid gastropods to
      hypoxia and re-oxygenation.
AB  - Changes in the levels of carbohydrate, lipid, protein and anaerobic metabolites
      (succinate, lactate, acetate, fumarate and propionate), upon exposure to hypoxia
      (1.5 mg O2 l(-1)) and after reoxygenation in subtidal gastropods Nassarius
      siquijorensis and N. conoidalis, were compared. A significant decrease of the
      glycogen content was observed under hypoxia in N. conoidalis but not in N.
      siquijorensis. A greater increase in the concentrations of anaerobic metabolites
      was observed in N. conoidalis under hypoxia, and their levels did not return to
      baseline after returning to normoxia for 24h. In contrast, a lower rate of
      accumulation of the metabolites was observed in N. siquijorensis, and complete
      recovery from anaerobic metabolism was observed after reoxygenation. The results
      lend further support to the role of hypoxia in governing the different
      distributional patterns between the two subtidal gastropods in Hong Kong waters.

PMID- 24680716
TI  - Functional and molecular characterization of a lipopeptide surfactant from the
      marine sponge-associated eubacteria Bacillus licheniformis NIOT-AMKV06 of Andaman
      and Nicobar Islands, India.
AB  - The production of a lipopeptide surfactant from the sponge-associated eubacteria
      Bacillus licheniformis NIOT-AMKV06 from the Andaman and Nicobar Islands was
      investigated. The highest production was attained with glucose and yeast extracts
      as the carbon and nitrogen sources (1.789 mg mL(-1)), respectively. The
      surfactant was highly stable over a pH range of 5.0-10 and a temperature range of
      20-70 degrees C with high NaCl concentrations. Excellent emulsification activity
      was exhibited by the purified surfactant with crude oil, kerosene, and diesel. A
      two-fold increase in surfactant production (3.0 mg mL(-1)) was observed using the
      newly formulated medium in this study. The surfactant biosynthesis gene cluster
      (sfp, sfpO, and srfA) from B. licheniformis NIOT-AMKV06 was heterologously
      expressed in Escherichia coli, and the production was increased three-fold (11.78
      g L(-1)) over the original strain. The results confirm the potential of the
      surfactant for use in bioremediation of hydrocarbons in a marine environment and
      for enhanced oil recovery. To our knowledge, this is the first report on the
      ability of a hydrocarbon degrading B. licheniformis from marine sponges for the
      biosynthesis of a potent lipopeptide surfactant possessing characteristics of
      maximum stability, outstanding surfactant activity, and exceptional emulsifying
      capability.

PMID- 24680717
TI  - Petroleum hydrocarbons in water from a Brazilian tropical estuary facing
      industrial and port development.
AB  - A fast paced industrial and port development has occurred at Suape Estuary,
      Northeast Brazil, but no information about hydrocarbon concentrations in water is
      available to this area. Considering that, the contamination level of Suape was
      determined by UV-Fluorescence in terms of dissolved and/or dispersed petroleum
      hydrocarbons (DDPHs), during wet and dry seasons. DDPHs ranged between 0.05 and
      4.59 MUg L(-1) Carmopolis oil equivalents and 0.01-1.39 MUg L(-1) chrysene
      equivalents, indicating DDPHs close to a baseline contamination level. Some
      relatively high concentrations (>1 MUg L(-1)) were probably associated with
      shipyard operations (hull paintings and ship docking), pollutants remobilization
      by dredging operations, occasional industrial discharges and oil derivatives
      released by vessels. DDPHs concentrations were lower in the wet season suggesting
      that the increased dilution rates caused by rainfall dominated upon the wet
      deposition of atmospheric combustion-derived PAHs process. Results in this study
      may be used as baseline to further studies in this area.

PMID- 24680718
TI  - Confidence rating for eutrophication assessments.
AB  - Confidence of monitoring data is dependent on their variability and
      representativeness of sampling in space and time. Whereas variability can be
      assessed as statistical confidence limits, representative sampling is related to
      equidistant sampling, considering gradients or changing rates at sampling gaps.
      By the proposed method both aspects are combined, resulting in balanced results
      for examples of total nitrogen concentrations in the German Bight/North Sea. For
      assessing sampling representativeness surface areas, vertical profiles and time
      periods are divided into regular sections for which individually the
      representativeness is calculated. The sums correspond to the overall
      representativeness of sampling in the defined area/time period. Effects of not
      sampled sections are estimated along parallel rows by reducing their confidence,
      considering their distances to next sampled sections and the interrupted
      gradients/changing rates. Confidence rating of time sections is based on maximum
      differences of sampling rates at regular time steps and related means of
      concentrations. 

PMID- 24680719
TI  - Trematode communities in cockles (Cerastoderma edule) of the Ria de Aveiro
      (Portugal): influence of inorganic contamination.
AB  - This work aims to assess the trematode parasites infecting the edible cockle
      Cerastoderma edule, collected in the Ria de Aveiro lagoon, one of the most
      relevant biodiversity hotspots of the Western Iberia, and evaluate the
      relationship between the observed patterns and environmental descriptors. A total
      of 11 of the 16 trematode species known to infect C. edule were identified,
      including Himasthla continua and Psilostomum brevicolle as new occurrences in
      this lagoon. Parvatrema minutum was the most abundant and dominant species.
      Species richness and prevalence were high. The relationship between trematode
      species abundance, intensity and prevalence, and also environmental variables,
      showed that most parasites preferred muddy sand areas with euhaline conditions in
      opposition to areas with contamination and/or distant from the lagoon entrance.
      This study highlighted the good ecological status of the ecosystem and the
      transitional biogeographic characteristics of the western Portuguese coast where
      northern and subtropical faunas can coexist. 

PMID- 24680720
TI  - Peripheral quantitative computed tomography measures are associated with adult
      fracture risk: the Hertfordshire Cohort Study.
AB  - Peripheral quantitative computed tomography (pQCT) captures novel aspects of bone
      geometry that may contribute to fracture risk and offers the ability to measure
      both volumetric bone mineral density (vBMD) and a separation of trabecular and
      cortical compartments of bone, but longitudinal data relating measures obtained
      from this technique to incident fractures are lacking. Here we report an analysis
      from the Hertfordshire Cohort Study, where we were able to study associations
      between measures obtained from pQCT and DXA in 182 men and 202 women aged 60-75
      years at baseline with incident fractures over 6 years later. Among women, radial
      cortical thickness (HR 1.72, 95% CI 1.16, 2.54, p=0.007) and cortical area (HR
      1.91, 95% CI 1.27, 2.85, p=0.002) at the 66% slice were both associated with
      incident fractures; these results remained significant after adjustment for
      confounders (age, BMI, social class, cigarette smoking and alcohol consumption,
      physical activity, dietary calcium, HRT and years since menopause). Further
      adjustment for aBMD made a little difference to the results. At the tibia,
      cortical area (HR 1.58, 95% CI 1.10, 2.28, p=0.01), thickness (HR 1.49, 95% CI
      1.08, 2.07, p=0.02) and density (HR 1.64, 95% CI 1.18, 2.26, p=0.003) at the 38%
      site were all associated with incident fractures with the cortical area and
      density relationships remaining robust to adjustment for the confounders listed
      above. Further adjustment for aBMD at this site did lead to attenuation of
      relationships. Among men, tibial stress-strain index (SSI) was predictive of
      incident fractures (HR 2.30, 95% CI 1.28, 4.13, p=0.005). Adjustment for
      confounding variables and aBMD did not render this association non-significant.
      In conclusion, we have demonstrated relationships between measures of bone size,
      density and strength obtained by pQCT and incident fracture. These relationships
      were attenuated but in some cases remained significant after adjustment for BMD
      measures obtained by DXA, suggesting that some additional information may be
      conferred by this assessment.

PMID- 24680721
TI  - Bone marrow blood vessel ossification and "microvascular dead space" in rat and
      human long bone.
AB  - Severe calcification of the bone microvascular network was observed in rats,
      whereby the bone marrow blood vessels appeared ossified. This study sought to
      characterize the magnitude of ossification in relation to patent blood vessels
      and adipocyte content in femoral diaphyses. Additionally, this study confirmed
      the presence of ossified vessels in patients with arteriosclerotic vascular
      disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8)
      and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium
      sulfate to visualize patent bone marrow blood vessels. Femoral shafts were
      processed for bone histomorphometry to quantify ossified (Goldner's Trichrome)
      and calcified (Alizarin Red) vessels. Adipocyte content was also determined.
      Additional femora (n=5/age group) were scanned via MUCT to quantify microvascular
      ossification. Bone marrow blood vessels from the rats and the human patients were
      also isolated and examined via microscopy. Ossified vessels (rats and humans) had
      osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning
      into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old
      vs. young rats. Calcified and ossified vessel volumes per tissue volume and
      calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%,
      375% and 263%, respectively, in the old vs. young rats. Ossified and patent
      vessel number was higher (171%) and lower (40%), respectively, in the old vs.
      young rats. Finally, adipocyte volume per patent vessel volume was higher (86%)
      with age. This study is the first to report ossification of bone marrow blood
      vessels in rats and humans. Ossification presumably results in "microvascular
      dead space" in regard to loss of patency and vasomotor function as opposed to
      necrosis. Progression of bone microvascular ossification may provide the common
      link associated with age-related changes in bone and bone marrow. The clinical
      implications may be evident in the difficulties treating bone disease in the
      elderly.

PMID- 24680722
TI  - Auditory observation of stepping actions can cue both spatial and temporal
      components of gait in Parkinson's disease patients.
AB  - OBJECTIVES: A common behavioural symptom of Parkinson's disease (PD) is reduced
      step length (SL). Whilst sensory cueing strategies can be effective in increasing
      SL and reducing gait variability, current cueing strategies conveying spatial or
      temporal information are generally confined to the use of either visual or
      auditory cue modalities, respectively. We describe a novel cueing strategy using
      ecologically-valid 'action-related' sounds (footsteps on gravel) that convey both
      spatial and temporal parameters of a specific action within a single cue.
      METHODS: The current study used a real-time imitation task to examine whether PD
      affects the ability to re-enact changes in spatial characteristics of stepping
      actions, based solely on auditory information. In a second experimental session,
      these procedures were repeated using synthesized sounds derived from recordings
      of the kinetic interactions between the foot and walking surface. A third
      experimental session examined whether adaptations observed when participants
      walked to action-sounds were preserved when participants imagined either real
      recorded or synthesized sounds. RESULTS: Whilst healthy control participants were
      able to re-enact significant changes in SL in all cue conditions, these
      adaptations, in conjunction with reduced variability of SL were only observed in
      the PD group when walking to, or imagining the recorded sounds. CONCLUSIONS: The
      findings show that while recordings of stepping sounds convey action information
      to allow PD patients to re-enact and imagine spatial characteristics of gait,
      synthesis of sounds purely from gait kinetics is insufficient to evoke similar
      changes in behaviour, perhaps indicating that PD patients have a higher threshold
      to cue sensorimotor resonant responses.

PMID- 24680723
TI  - I give you a cup, I get a cup: a kinematic study on social intention.
AB  - While affordances have been intensively studied, the mechanisms according to how
      their activation is modulated by context are poorly understood. We investigated
      how the Agent's reach-to-grasp movement towards a target-object (e.g. a can) is
      influenced by the other's interaction with a second object
      (manipulative/functional) and by his/her eye-gaze communication. To manipulate
      physical context we showed participants two objects that could be linked by a
      spatial relation (e.g. can-knife, typically found in the same context), or by
      different functional relations. The functional relations could imply an action to
      perform with another person (functional-cooperative: e.g. can-glass), or on our
      own (functional-individual: e.g. can-straw). When objects were not related (e.g.
      can-toothbrush) participants had to refrain from responding. In order to respond,
      in the giving condition participants had to move the target object towards the
      other person, in the getting condition towards their own body. When participants
      (Agents) performed a reach-to-grasp movement to give the target object, in
      presence of eye-gaze communication they reached the wrist's acceleration peak
      faster if the Other previously interacted with the second object in accordance
      with its conventional use. Consistently participants reached faster the MFA when
      the objects were related by a functional-individual than a functional-cooperative
      relation. The Agent's getting response strongly affected the grasping component
      of the movement: in case of eye-gaze sharing, MFA was greater when the other
      previously performed a manipulative than a functional grip. Results reveal that
      humans have developed a sophisticated capability in detecting information from
      hand posture and eye-gaze, which are informative as to the Agent's intention. 

PMID- 24680724
TI  - Cross-omics gene and protein expression profiling in juvenile female mice
      highlights disruption of calcium and zinc signalling in the brain following
      dietary exposure to CB-153, BDE-47, HBCD or TCDD.
AB  - The present study assessed if eating a diet of fish, spiked with persistent
      organic pollutants (POPs), affects gene and protein expression in the maturing
      mouse brain. Juvenile female Balb/c mice (22 days of age) were exposed for 28
      days to fish-based diets spiked with the dioxin 2,3,7,8-tetrachlorodibenzodioxin
      (TCDD) or the non dioxin-like (NDL) chemicals hexabromocyclodocecane (HBCD),
      2,2'4,4'-tetrabromodiphenylether (BDE-47) or 2,2'4,4',5,5'-hexachlorobiphenyl (CB
      153) at doses approximating their respective lowest observed adverse effect
      levels (LOAEL). It was found that all POPs elicited changes in neural gene and
      protein expression profiles. Bioinformatic analysis of gene expression data
      highlighted the importance of the aryl hydrocarbon receptor (AHR) in dioxin
      toxicity and revealed that zinc regulation in the brain is targeted by TCDD
      through the AHR. Calcium homeostasis was affected by both TCDD and the NDL
      chemicals. In contrast to the transcriptomic analysis, the proteomics data did
      not allow for a clear distinction between DL and NDL responses in the juvenile
      brain but indicated that proteins associated with excitotoxicity were affected in
      all exposure groups. Integrated interpretation of data led to the conclusion that
      the dietary contaminants investigated in the present study breach the blood brain
      barrier (BBB) and accumulate in the juvenile brain where they may induce
      excitotoxic insults by dysregulation of the otherwise tightly controlled
      homeostasis of calcium and zinc. Overall, the findings of the present study
      highlight the need for further assessment of the risks associated with early life
      exposure to foodborne POPs. 

PMID- 24680725
TI  - Treatment-resistant schizophrenia and DAT and SERT polymorphisms.
AB  - One fifth to one third of all patients diagnosed with schizophrenia are resistant
      to drug treatment, which makes it a major clinical challenge. Genetic studies
      have focused on the association between treatment resistant schizophrenia (TRS)
      and a number of candidate genes, including serotonin and dopamine system genes.
      We explored associations between carefully characterized TRS and DAT-VNTR, SERT
      PR and SERT-in2 polymorphisms. There were 173 patients enrolled in the study that
      were clinically evaluated using Positive and Negative Syndrome Scale and Clinical
      Global Impressions Scales and divided into two groups based on treatment
      resistance (92 patients in TRS group). Patients with a combination of SERT-in2 ll
      and DAT 9/10, 9/11, 9/9 and 6/6 genotypes were more likely to have TRS, compared
      to those with 10/10 or 10/12 genotype (OR=5.1; 95% CI=1.6-16.8). In the group of
      patients with DAT 10/10 or 10/12 genotype, those who also shared SERT-in2 ls or
      ss genotype were more likely to have TRS, compared to ll genotype carriers
      (OR=2.7; 95% CI=1.0-7.0). The model in which interaction between SERT-in2 and DAT
      polymorphisms is linked to TRS can possibly explain contradictory previous
      results regarding role of DAT and SERT in TRS, but further research is needed. 

PMID- 24680727
TI  - A new missense mutation in FGF23 gene in a male with hyperostosis
      hyperphosphatemia syndrome (HHS).
AB  - Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare autosomal recessive
      metabolic disorder, characterized by recurrent painful swelling of long bones,
      periosteal new bone formation and cortical hyperostosis or intramedullary
      sclerosis, hyperphosphatemia and low intact fibroblast growth factor 23 (FGF23)
      protein levels. It is caused by mutations in 2 genes, N
      acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) and FGF23. We have
      performed mutation analysis of the GALNT3 and FGF23 genes in a patient with HHS
      and detected a homozygous mutation in exon 3 of FGF23 gene (NM_020638.2:
      c.471C>A) which results in amino acid change from phenylalanine 157 to leucin
      (p.F157L) in receptor interaction site.

PMID- 24680726
TI  - Conservation and divergence in the frog immunome: pyrosequencing and de novo
      assembly of immune tissue transcriptomes.
AB  - BACKGROUND: Frogs are a diverse group of vertebrates for which limited genomic
      resources are available. Natural frog populations face a multitude of threats,
      including habitat degradation, infectious disease, and environmental change.
      Characterizing the functional genomics of anuran tissues in general - and the
      immune system in particular - will enhance our knowledge of genetic and
      epigenetic responses to environmental threats and inform conservation and
      recovery efforts. RESULTS: To increase the number of species with genomic
      datasets and characterize gene expression in immune-related tissues, we sequenced
      the transcriptomes of three tissues from two frogs (Espadarana prosoblepon and
      Lithobates yavapaiensis) on the Roche 454 GS FLX platform. Our sequencing
      produced 8881 E. prosoblepon and 5428 L. yavapaiensis annotated gene products
      after de novo assembly and Gene Ontology classification. Transcripts of the
      innate and acquired immune system were expressed in all three tissues.
      Inflammatory response and acquired immunity transcripts were significantly more
      diverged between E. prosoblepon and L. yavapaiensis compared to innate immunity
      and immune system development transcripts. Immune-related transcripts did not
      show an overall elevated rate of functional evolution, with the exception of
      glycosyl proteases, which include lysozymes, central bacterial and fungal-killing
      enzymes of the innate immune system. CONCLUSIONS: The three frog transcriptomes
      provide more than 600 Mbp of new genomic data, and will serve as a valuable
      framework for future comparative studies of non-model anurans. Additionally, we
      show that immune gene divergence varies by functional group and that
      transcriptome studies can be useful in comparing rates of evolutionary change
      across gene families.

PMID- 24680728
TI  - Environmental enrichment induces changes in brain monoamine levels in gilthead
      seabream Sparus aurata.
AB  - It is generally accepted that environmental enrichment enhances the performance
      and improves welfare of animals kept in captivity. Similar results have been
      obtained for fish. It has been previously reported that the presence of Blue or
      Red-Brown Substrate (BS and RBS respectively) on tank bottom resulted in growth
      enhancement and suppression of aggressive behavior of gilthead seabream Sparus
      aurata compared to Green Substrate (GS) and tanks without modifications (Control
      C). In an attempt to identify the underlying mechanisms, in the present study the
      effects of this environmental enrichment on brain monoamine neurotransmitters and
      fatty acids of gilthead seabream were evaluated. BS and RBS fish had lower
      serotonergic activity (5-HIAA/5-HT), resulting mainly from lower 5
      hydroxyindoleacetic acid (5-HIAA) levels. BS fish also had lower serotonin levels
      compared to all other treatments. Brain noradrenaline (NA) levels did not show
      significant differences between substrate treatments and control. Brain dopamine
      (DA) levels were lowest in BS and RBS fish, higher in GS fish and highest in C
      fish. No differences were observed for dopamine metabolites or dopaminergic
      activity. Moreover, brain NA was negatively correlated with body weight in BS
      fish and positively correlated in RBS and C fish. A positive correlation was also
      observed for brain DA with body weight in RBS fish. No differences were observed
      for brain fatty acids. Present results support the hypothesis that the beneficial
      effects of the presence of BS and RBS are related to altered social interactions
      and indicate the establishment of a less stressful social organization in
      enriched-reared fish groups. 

PMID- 24680730
TI  - Expression of soluble and active interferon consensus in SUMO fusion expression
      system in E. coli.
AB  - Protein production can be improved if methods for soluble protein expression are
      developed. Interferon consensus (IFN-con) is used to treat hepatitis C. IFN-con
      has superior activity compared to other clinically used interferon alpha
      subtypes. However IFN-con is a challenging protein to produce in a soluble form
      using an Escherichia coli expression system. Here we describe the expression of
      soluble and active recombinant IFN-con in E. coli. The IFN-con gene sequence was
      optimised for expression in E. coli, which was then cloned into the ChampionTM
      pET SUMO expression vector downstream of the SUMO fusion protein and under strong
      T7lac promoter. The SUMO-IFN-con fusion protein was efficiently expressed using
      the SHuffleTM E. coli strain and existed in soluble form as 86-88% of the total
      IFN-con. After removal of the SUMO fusion partner, approximately 50mg of
      recombinant IFN-con of at least 98% purity (by RP-HPLC) was obtained from a 1L
      fermentation culture. Using an A549/EMCV antiviral assay, the specific activity
      of the recombinant IFN-con was determined to be 960*10(6) IU/mg as calculated to
      NIBSC standard for IFN-con (3*10(5)pfu/mL virus titre). Comparison of the
      antiviral activity of the produced IFN-con to IFN alpha-2a showed that IFN-con
      displays 2.8 times greater activity, which is in good agreement with what has
      been reported in the literature for pure protein. IFN-con expression in a soluble
      form from E. coli allowed us to use a simple, two-step purification process to
      yield highly pure and active IFN-con which is more efficient than obtaining IFN
      con from inclusion bodies. 

PMID- 24680729
TI  - Prematurely delivered rats show improved motor coordination during sensory-evoked
      motor responses compared to age-matched controls.
AB  - The amount of postnatal experience for perinatal rats was manipulated by
      delivering pups one day early (postconception day 21; PC21) by cesarean delivery
      and comparing their motor behavior to age-matched controls on PC22 (the typical
      day of birth). On PC22, pups were tested on multiple measures of motor
      coordination: leg extension response (LER), facial wiping, contact righting, and
      fore- and hindlimb stepping. The LER and facial wiping provided measures of
      synchronous hind- and forelimb coordination, respectively, and were sensory
      evoked. Contact righting also was sensory-evoked and provided a measure of axial
      coordination. Stepping provided a measure of alternated forelimb and hindlimb
      coordination and was induced with the serotonin receptor agonist quipazine. Pups
      that were delivered prematurely and spent an additional day in the postnatal
      environment showed more bilateral limb coordination during expression of the LER
      and facial wiping, as well as a more mature righting strategy, compared to
      controls. These findings suggest that experience around the time of birth shapes
      motor coordination and the expression of species-typical behavior in the
      developing rat. 

PMID- 24680731
TI  - High-throughput cloning, expression and purification of glycoside hydrolases
      using Ligation-Independent Cloning (LIC).
AB  - Recent advances in DNA sequencing techniques have led to an explosion in the
      amount of available genome sequencing data and this provided an inexhaustible
      source of uncharacterized glycoside hydrolases (GH) to be studied both
      structurally and enzymatically. Ligation-Independent Cloning (LIC), an
      interesting alternative to traditional, restriction enzyme-based cloning, and
      commercial recombinatorial cloning, was adopted and optimized successfully for a
      high throughput cloning, expression and purification pipeline. Using this
      platform, 130 genes encoding mainly uncharacterized glycoside hydrolases from 13
      different organisms were cloned and submitted to a semi-automated protein
      expression and solubility screening in Escherichia coli, resulting in 73 soluble
      targets. The high throughput approach proved to be a powerful tool for production
      of recombinant glycoside hydrolases for further structural and biochemical
      characterization and confirmed that thioredoxin fusion tag (TRX) is a better
      choice to increase solubility of recombinant glycoside hydrolases expressed in E.
      coli, when compared to His-tag alone. 

PMID- 24680732
TI  - Biochemical properties of glycosylation and characterization of a histidine acid
      phosphatase (phytase) expressed in Pichia pastoris.
AB  - Phytases catalyze the cleavage of phosphate groups from phytic acid. Here, we
      have studied the effects of glycosylation on the properties of Aspergillus
      japonicus C03 phytase expressed in Pichia pastoris. The enzyme ORF of 1338
      nucleotides was cloned from genomic DNA, and encoded a secreted mature protein of
      446 amino acids, which included the sequence motif RHGXRX and dipeptide HD,
      classifying the phytase as a histidine acid phosphate. After transformation and
      72h of induction, P.pastoris GS115 expressed a 75kDa protein showing 526U/mg
      phytase activity and 143mg/L of protein. The amino acid sequence showed 8 and 3
      potential N- and O-glycosylation sites, respectively. Analysis by ESMS showed two
      glycoform masses of 75,467 and 72,793, which after deglycosylation decreased to
      54,327 and 54,128, respectively, indicating a carbohydrate content of 27-30%. A
      single GlcNAc was assigned at Asn6, Asn38, Asn84, Asn99, Asn209, Asn218, Asn355
      and Asn367. The recombinant phytase showed maximum activity at 50 degrees C, a
      half-life of 40min, and farUVCD spectroscopy indicated a secondary structure rich
      in alpha-helix. Thermal denaturation analyses reveal the melting temperature
      varied from 50 degrees C at pH 6 to a maximum of 66 degrees C at pH 3 and pH 4. 

PMID- 24680733
TI  - When less becomes more: optimization of protein expression in HEK293-EBNA1 cells
      using plasmid titration - a case study for NLRs.
AB  - Transient transfection of the human HEK293-EBNA1 cell line using
      polyethyleneimine is widely adopted for recombinant protein production. Whereas
      high expression of many targets is achieved, purification yields of some highly
      expressed proteins remain low due to aggregation. We hypothesized that for these
      proteins the expression rates achieved at standard transfection conditions are
      too high, causing an overload of the protein folding machinery. Here we present
      plasmid titration as an efficient method to vary expression rates for the
      optimization of soluble protein expression. In plasmid titration a dilution
      series of expression vector mixed with dummy plasmid is transfected in small
      scale cultures. Application to GFP shows that plasmid titration achieves a wide
      range of expression levels while maintaining high transfection efficiencies even
      at 500-fold plasmid dilution. Application of plasmid titration to selected Nod
      like receptors (NLRs), which at standard conditions are highly expressed but
      poorly soluble, delays the onset of NLR aggregation and improves cell viability
      and the buildup of biomass. The amount of soluble protein depends on the
      combination of dilution factor and harvest day in a protein specific manner. For
      NOD1 50-fold plasmid dilution increases the amount of soluble protein
      approximately 5-fold. Due to its association with chaperones at all dilution
      factors tested we were unable to purify NOD1 to homogeneity. For NLRC4, which did
      not associate with chaperones, 10-fold plasmid dilution increased the
      purification yield 2-fold. This improvement, obtained with minimal effort due to
      the simplicity of the method, shows that reducing total expression may increase
      soluble protein yield. 

PMID- 24680734
TI  - Smoking and cerebral aneurysms--potential pathobiologic mechanisms.

PMID- 24680735
TI  - Age versus nutritional state in the development of central leptin resistance.
AB  - Leptin, a catabolic adiposity signal acts in the hypothalamus via suppressing
      food intake and inducing hypermetabolism. Age and obesity are accompanied by
      leptin resistance. The present study aimed to clarify which components of the
      catabolic leptin effects are influenced most strongly by aging and which ones by
      nutritional state-induced alterations in body composition. In our biotelemetric
      study the effects of a 7-day intracerebroventricular leptin infusion on various
      parameters of energy balance (food intake, body weight, oxygen consumption, heart
      rate and body temperature) were analyzed in male Wistar rats of different age
      groups (from 3 to 24 months) and nutritional states (normally fed, diet-induced
      obese and calorie-restricted). Leptin resistance of older animals affected
      hypermetabolic actions, whereas leptin induced anorexia in all age-groups. Weight
      reducing effect of leptin diminished in middle-aged and aging animals to become
      significant again in the oldest group. In diet-induced obese rats leptin-induced
      hypermetabolism of the young rats and hypermetabolism plus anorexia of the aging
      ones were suppressed. Calorie-restriction reduced body weight and fat mass to a
      similar extent in all age-groups. It strongly enhanced leptin-induced
      hypermetabolism at all ages and prevented the manifestation of anorexigenic
      actions of leptin with the exception of the oldest group. This latter finding
      suggests an unexpected increase of responsiveness to anorexigenic leptin actions
      in old rats. Accordingly, anorexia and hypermetabolism change in disparate ways
      with aging. Nutritional state predominantly influences hypermetabolic leptin
      actions. Resistance to both hypermetabolic and anorexigenic actions were promoted
      by obesity, while calorie-restriction enhanced responsiveness to leptin,
      especially in old rats. 

PMID- 24680736
TI  - Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical
      obesity in mice.
AB  - OBJECTIVE: Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy
      homeostasis. Single NPY or dynorphin deletion reduces food intake or increases
      fat loss. Future developments of obesity therapeutics involve targeting multiple
      pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis
      independently, thus double NPY and dynorphin ablation would result in greater
      weight and/or fat loss than the absence of NPY or dynorphin alone. DESIGN AND
      METHODS: We generated single and double NPY and dynorphin knockout mice
      (NPYDelta, DYNDelta, NPYDYNDelta) and compared body weight, adiposity, feeding
      behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP
      1) expression to wildtype counterparts. RESULTS: Body weight and adiposity were
      significantly increased in NPYDYNDelta, but not in NPYDelta or DYNDelta. This was
      not due to increased food intake or altered UCP-1 expression, which were not
      significantly altered in double knockouts. NPYDYNDelta mice demonstrated
      increased body weight loss after a 24-h fast, with no effect on serum glucose
      levels after glucose injection. CONCLUSIONS: Contrary to the predicted phenotype
      delineated from single knockouts, double NPY and dynorphin deletion resulted in
      heavier mice, with increased adiposity, despite no significant changes in food
      intake or UCP-1 activity. This indicates that combining long-term opioid
      antagonism with blockade of NPY-ergic systems may not produce anti-obesity
      effects.

PMID- 24680737
TI  - Model predictive control for optimally scheduling intermittent androgen
      suppression of prostate cancer.
AB  - Mathematical modeling of prostate cancer under intermittent androgen suppression
      revealed that we may be able to delay relapse by optimally scheduling the hormone
      therapy for each patient. However, our previous study showed the difficulty of
      the scheduling by minimizing the maximal tumor growth rate because the transient
      dynamics is also important and can help to delay the relapse for a finite time.
      Here, we propose to use model predictive control for scheduling intermittent
      androgen suppression. We find that model predictive control tends to delay the
      relapse of prostate specific antigen more than the method with minimizing the
      maximal tumor growth rate. Therefore, model predictive control is a promising
      approach for practically applying the mathematical model to optimally schedule
      intermittent androgen suppression. 

PMID- 24680738
TI  - On the mechanism underlying tellurite reduction by Aeromonas caviae ST
      dihydrolipoamide dehydrogenase.
AB  - The dihydrolipoamide dehydrogenase (LpdA) from the tellurite-resistant bacterium
      Aeromonas caviae ST reduces tellurite to elemental tellurium. To characterize
      this NADH-dependent activity, the A. caviae lpdA gene was subjected to site
      directed mutagenesis and genes containing C45A, H322Y and E354K substitutions
      were individually transformed into Escherichia coli Deltalpd. Cells expressing
      the modified genes exhibited decreased pyruvate dehydrogenase, dihydrolipoamide
      dehydrogenase and TR activity regarding that observed with the wild type A.
      caviae lpdA gene. In addition, cells expressing the altered lpdA genes showed
      increased oxidative stress levels and tellurite sensitivity than those carrying
      the wild type counterpart. The involvement of Cys residues in LpdA's TR activity
      was analyzed using specific inhibitors that interact with catalytic cysteines
      and/or disulfide bridges such as aurothiomalate, zinc or nickel. TR activity of
      purified LpdA was drastically affected by these compounds. Since LpdA belongs to
      the flavoprotein family, the involvement of the FAD/NAD(P)(+)-binding domain in
      TR activity was determined. FAD removal from purified LpdA results in loss of TR
      activity, which was restored with exogenously added FAD. Substitutions in E354,
      involved in FAD/NADH binding, resulted in low TR activity because of flavin loss.
      Finally, changing H322 (involved in NAD(+)/NADH binding) by tyrosine also
      resulted in altered TR activity.

PMID- 24680740
TI  - Rapid chromosomal evolution in a morphologically cryptic radiation.
AB  - Cryptic species occur within most of the major taxonomic divisions, and a current
      challenge is to determine why some lineages have more cryptic species than
      others. It is expected that cryptic species are more common in groups where there
      are life histories or genetic architectures that promote speciation in the
      absence of apparent morphological differentiation. Chromosomal rearrangements
      have the potential to lead to post-zygotic isolation and might be an important
      factor leading to cryptic species. Here we investigate the potential role of
      chromosomal change in driving speciation in the karyotypically diverse scale
      insect genus Apiomorpha, focussing on four species placed in the same species
      group (the A. minor species group Gullan, 1984). Using mitochondrial and nuclear
      DNA sequence data, we find that Apiomorpha minor is not monophyletic and consists
      of at least nine cryptic species. Diploid chromosome counts range from 2n=4 to
      2n=84 across the four currently recognized species, and some of the chromosomal
      variation exists in the absence of other genetic or host use differences,
      consistent with karyotypic changes being involved in lineage divergence and the
      generation of cryptic species. 

PMID- 24680739
TI  - Dual control of seasonal time keeping in male and female juvenile European
      hamsters.
AB  - In contrast to photoperiodic rodent species, adult circannual European hamsters
      (Cricetus cricetus) do not rely on melatonin as transducer of the photoperiodic
      message. Instead, seasonal entrainment involves a special circadian organisation
      which characterizes a photoperiod-sensitive phase. When days shorten a precise
      activity pattern ("summer pattern") switches to a weak or arrhythmic "winter
      pattern". At the very same day gonadal regression is initiated and the circannual
      clock is reset. In contrast to this difference in photoperiodic time measurement,
      the broad time span in which offspring are born and the birth-season dependent
      timing of puberty is similar to photoperiodic rodents. We investigated how
      juvenile European hamsters measure photoperiod to situate themselves at the
      proper position in the annual cycle. Activity and 6-sulphatoxymelatonin (aMT6s)
      excretion were recorded in pups of five litters born at different seasons. Pups
      of all litters showed an activity pattern identical with the adults' summer
      pattern until postnatal day 78, suggesting that the pathway known to reset the
      circannual clock in adults is functional. The synchronous start of reproduction
      in yearlings supports this. However, since puberty and gonadal regression
      occurred before the switch in the activity pattern, the timing of reproduction in
      the birth year must be controlled by other means. As in photoperiodic species
      melatonin might be involved, since the aMT6s excretion showed daily and seasonal
      rhythms from early life on. 

PMID- 24680741
TI  - Molecular systematics and historical biogeography of the green lizards (Lacerta)
      in Greece: insights from mitochondrial and nuclear DNA.
AB  - The green lizards of the genus Lacerta (Sauria, Lacertidae) comprise nine
      recognized species, which in Europe are mainly restricted to the southern
      peninsulas. Four of them (L. trilineata, L. viridis, L. bilineata and L. agilis)
      occur in Greece. The uncertainty of morphological diversification renders the
      taxonomic assignment into species and subspecies problematic. In this study
      sequence data derived from two mitochondrial (cytochrome b and 16S rRNA) genes
      and one nuclear (NKTR) gene were used to (a) evaluate the taxonomic status of the
      genus Lacerta in Greece with emphasis on L. trilineata group and (b) investigate
      the evolutionary history of the genus through the application of phylogenetic and
      phylogeographic analyses, using Gallotia and Timon as outgroups. The phylogenetic
      analyses revealed the existence of four major clades. The first clade corresponds
      to L. trilineata group, the second to L. media, the third to L. agilis and the
      fourth to a complex of L. viridis and L. bilineata. However, the produced
      phylogenetic relationships are not congruent with the current taxonomy,
      especially in the first clade in which L. trilineata appeared to be paraphyletic
      in regard to L. pamphylica. Six distinct lineages were inferred within L.
      trilineata, despite the current recognition of nine morphological subspecies, the
      genetic differentiation of which exceeds that of other Lacerta species, imposing
      a thorough taxonomic revision of the species. Our results suggested a rapid
      diversification of L. trilineata group during the late Miocene. We believe that
      the present distribution of the genus in Greece is the result of several
      dispersal and vicariant events that took place during the late Miocene and early
      Pliocene. 

PMID- 24680742
TI  - Altered brainstem auditory evoked potentials in a rat central sensitization model
      are similar to those in migraine.
AB  - Migraine symptoms often include auditory discomfort. Nitroglycerin (NTG)
      triggered central sensitization (CS) provides a rodent model of migraine, but
      auditory brainstem pathways have not yet been studied in this example. Our
      objective was to examine brainstem auditory evoked potentials (BAEPs) in rat CS
      as a measure of possible auditory abnormalities. We used four subdermal
      electrodes to record horizontal (h) and vertical (v) dipole channel BAEPs before
      and after injection of NTG or saline. We measured the peak latencies (PLs),
      interpeak latencies (IPLs), and amplitudes for detectable waveforms evoked by 8,
      16, or 32 kHz auditory stimulation. At 8 kHz stimulation, vertical channel
      positive PLs of waves 4, 5, and 6 (vP4, vP5, and vP6), and related IPLs from
      earlier negative or positive peaks (vN1-vP4, vN1-vP5, vN1-vP6; vP3-vP4, vP3-vP6)
      increased significantly 2h after NTG injection compared to the saline group.
      However, BAEP peak amplitudes at all frequencies, PLs and IPLs from the
      horizontal channel at all frequencies, and the vertical channel stimulated at 16
      and 32 kHz showed no significant/consistent change. For the first time in the rat
      CS model, we show that BAEP PLs and IPLs ranging from putative bilateral medial
      superior olivary nuclei (P4) to the more rostral structures such as the medial
      geniculate body (P6) were prolonged 2h after NTG administration. These BAEP
      alterations could reflect changes in neurotransmitters and/or hypoperfusion in
      the midbrain. The similarity of our results with previous human studies further
      validates the rodent CS model for future migraine research.

PMID- 24680743
TI  - Allopurinol reduces levels of urate and dopamine but not dopaminergic neurons in
      a dual pesticide model of Parkinson's disease.
AB  - Robust epidemiological data link higher levels of the antioxidant urate to a
      reduced risk of developing Parkinson's disease (PD) and to a slower rate of its
      progression. Allopurinol, an inhibitor of xanthine oxidoreductase (XOR), blocks
      the oxidation of xanthine to urate. The present study sought to determine whether
      lowering levels of urate using allopurinol results in exacerbated neurotoxicity
      in a dual pesticide mouse model of PD. Although oral allopurinol reduced serum
      and striatal urate levels 4-fold and 1.3-fold, respectively, it did not alter the
      multiple motor deficits induced by chronic (7 week) intermittent (biweekly)
      exposure to intraperitoneal Paraquat (PQ) plus Maneb (MB). However, striatal
      dopamine content, which was unaffected after either allopurinol or chronic
      pesticide exposure alone, was significantly reduced by 22% in mice exposed to the
      combination. Stereological assessment showed that the numbers of dopaminergic
      nigral neurons were significantly reduced by 29% and the tyrosine hydroxylase
      (TH) negative neurons unaffected after PQ+MB treatments. This reduction in TH
      positive neurons was not affected by allopurinol treatment. Of note, despite the
      expectation of exacerbated oxidative damage due to the reduction in urate,
      protein carbonyl levels, a marker of oxidative damage, were actually reduced in
      the presence of allopurinol. Overall, allopurinol lowered urate levels but did
      not exacerbate dopaminergic neuron degeneration, findings suggesting that basal
      levels of urate in mice do not appreciably protect against oxidative damage and
      neurotoxicity in the PQ+MB model of PD, and/or that allopurinol produces an
      antioxidant benefit offsetting its detrimental urate-lowering effect.

PMID- 24680745
TI  - Chronic intermittent hypoxic preconditioning suppresses pilocarpine-induced
      seizures and associated hippocampal neurodegeneration.
AB  - Mild brief hypoxia can protect against neuronal damage induced by epileptic
      seizures, at least in part by inhibiting apoptosis. Further elucidation of the
      antiepileptic mechanisms and optimization of the conditioning protocols are
      required before this strategy can be considered for clinical intervention. In
      this study, we compared the effects of different hypoxic preconditioning
      protocols on spontaneous recurrent seizures (SRS), intracellular free calcium
      concentration ([Ca(2+)]i), and apoptosis rate following pilocarpine-induced
      status epilepticus (SE). Male Sprague Dawley rats were subjected to either
      chronic intermittent hypobaric hypoxia (CIHH) or chronic intermittent normobaric
      hypoxia (CINH) (both for 6h/day * 28 consecutive days) prior to pilocarpine
      induced SE. The possible anticonvulsant and neuroprotective effects of CIHH and
      CINH were compared by video monitoring of behavioral seizure activity (frequency,
      delay), Nissl staining and Fluoro-Jade B (FJB) staining to examine changes in the
      morphology of hippocampal pyramidal neurons, and flow cytometry to detect the
      quantification of [Ca(2+)]i and cell apoptosis. Both hypoxic preconditioning
      protocols reduced the frequency and severity of SRS, suppressed post-ictal
      [Ca(2+)]i elevations, and inhibited neuronal apoptosis in the rat hippocampus
      compared to pilocarpine alone, but CIHH was more effective than CINH. Thus, mild
      hypoxic pretreatment, particularly when delivered as CIHH, may be a novel
      strategy for the clinical prevention and treatment of epilepsy.

PMID- 24680744
TI  - Superior longitudinal fasciculus and language functioning in healthy aging.
AB  - Structural deterioration of brain tissue in older adults is thought to be
      responsible for the majority of age-related cognitive decline. Disruption of
      widespread cortical networks due to a loss of axonal integrity may also play an
      important role. Research examining correlations between structural change and
      functional decline has focused heavily on working memory, processing speed, and
      executive processes while other aspects of cognition, such as language
      functioning, have received less attention. The current study aimed to determine
      whether age-related changes in the superior longitudinal fasciculus (SLF), are
      responsible for the deterioration in language functioning associated with age.
      Subjects included 112 right-handed volunteers (ages 19-76). For each subject, the
      SLF of the left hemisphere was reconstructed from diffusion tensor images (DTI).
      Mean fractional anisotropy (FA) values were extracted from parietal (SLFp) and
      temporal (SLFt) bundles. Language functioning was measured using the Peabody
      Picture Vocabulary Test (PPVT), Boston Naming Test (BNT), Controlled Oral Word
      Association Test (COWAT), and Semantic Fluency Test (SFT). Regression analyses
      revealed that males and females showed a different pattern of decline in FA
      across adulthood. For males, greater SLFt FA was significantly associated with
      increased COWAT performance, and there was a positive relationship between both
      age and SLFp FA with BNT scores. In females, greater SLFp FA was related to lower
      COWAT performance. Taken together, the results suggest that white matter
      integrity of the SLF follows a different pattern of decline in adulthood for
      males and females, and this decline differentially affects language functioning. 

PMID- 24680746
TI  - Improvement of human umbilical cord mesenchymal stem cell transplantation on
      glial cell and behavioral function in a neonatal model of periventricular white
      matter damage.
AB  - Periventricular white matter damage (PWMD) also termed periventricular
      leucomalacia in the preterm infant is of particular importance because no
      targeted therapy is presently available. Human umbilical cord mesenchymal stem
      cells (hUC-MSCs) have been studied in a variety of adult brain injury-related
      neurological disorders. Our aim was to determine whether hUC-MSC transplantation
      improves glial cell function in cerebral white matter and long-term behavioral
      function in a PWMD rat model. Rats on postnatal day (P) 3 underwent a permanent
      ligation of the left common carotid artery followed by 6% O2 for 4h. Immediately
      after the hypoxic-ischemic (HI), rats received a single intraperitoneal injection
      of hUC-MSCs, which were co-cultured with 5-bromodeoxyuridine (BrdU). BrdU(+)
      cells in the brain were tested 24h after transplantation. Second, rats received
      hUC-MSC treatment once a day for 3 consecutive days. Glial cells
      (oligodendrocytes, astrocytes and microglia) were examined on 7 and 18 days post
      HI, and behavioral outcomes were tested 27 days post-HI. Significantly, hUC-MSCs
      migrated mainly into the injured hemisphere. In addition, hUC-MSC treatment
      improved the long-term functional outcomes of rats, increased mature
      oligodendrocyte counts, and decreased the number of reactive astrocytes and
      activated microglia quantities after HI-induced damage in the premature brain.
      These results suggest that hUC-MSCs can pass through the blood-brain barrier and
      migrate towards the lesion site to improve brain damage. Therefore, hUC-MSCs have
      the potential to be utilized as a novel therapeutic strategy for PWMD.

PMID- 24680747
TI  - Methylphenidate enhances acquisition and retention of spatial memory.
AB  - Psychostimulants containing methylphenidate (MPH) are increasingly being used
      both on and off-label to enhance learning and memory. Still, almost no studies
      have investigated MPH's ability to specifically improve spatial or long-term
      memory. Here we examined the effect of training with 1 or 10mg/kg MPH on hidden
      platform learning in the Morris water maze. 10mg/kg MPH improved memory
      acquisition and retention, while 1mg/kg MPH improved memory retention. Taken
      together with prior evidence that low, clinically relevant, doses of MPH (0.01
      1mg/kg MPH) enhance fear memory we conclude that MPH broadly enhances memory. 

PMID- 24680748
TI  - Differential effects of angiotensin II receptor blockers on Abeta generation.
AB  - Angiotensin II receptor blockers (ARBs) are widely prescribed for the medication
      of systemic hypertension and congestive heart failure. It has been reported that
      ARBs can reduce the risk for the onset of Alzheimer's disease (AD) and have
      beneficial effects on dementia. Neurotoxic amyloid beta-protein (Abeta) is
      believed to play a causative role in the development of AD. However, whether ARBs
      regulate Abeta generation remains largely unknown. Here, we studied the effect of
      ARBs on Abeta generation and found that telmisartan significantly increased
      Abeta40 and Abeta42 generation, but decreased the Abeta42/Abeta40 ratio. However,
      losartan, valsartan and candesartan did not increase Abeta generation, while
      olmesartan significantly increased Abeta42 generation. We also found that
      telmisartan increased the Abeta generation through angiotensin type 1a receptor
      (AT1a) and the receptor-related phosphotidylinositide 3-kinases (PI3K) pathway.
      Our findings revealed the different effects of ARBs on Abeta generation and
      provide new evidence for the relationship between antihypertensive treatment and
      AD pathogenesis.

PMID- 24680749
TI  - Effects of amyloid beta-peptide fragment 31-35 on the BK channel-mediated K+
      current and intracellular free Ca2+ concentration of hippocampal CA1 neurons.
AB  - The present study characterizes the effects of Abeta31-35, a short active
      fragment of amyloid beta-peptide (Abeta), upon the BK channel-mediated K+ current
      and intracellular free Ca2+ concentration ([Ca2+]i) of freshly dissociated
      pyramidal cells from rat CA1 hippocampus by using whole-cell patch-clamp
      recording and single cell Ca2+ imaging techniques. The results show that: (1) in
      the presence of voltage- and ATP-gated K+ channel blockers application of 5.0 MUM
      Abeta31-35 significantly diminished transient outward K+ current amplitudes at
      clamped voltages between 0 and 45mV; (2) under the same conditions [Ca2+]i was
      minimally affected by 5.0 MUM but significantly increased by 12.5 MUM and 25 MUM
      Abeta31-35; and (3) when 25 MUM of a larger fragment of the amyloid beta-peptide,
      Abeta25-35, was applied, the results were similar to those obtained with the same
      concentration of Abeta31-35. These results indicate that Abeta31-35 is likely to
      be the shortest active fragment of the full Abeta sequence, and can be as
      effectively as the full-length Abeta peptide in suppressing BK-channel mediated
      K+ currents and significantly elevating [Ca2+]i in hippocampal CA1 neurons.

PMID- 24680750
TI  - Immunological and histological responses to sulfide in the crab Charybdis
      japonica.
AB  - In this study, immunological and histological responses of the crab Charybdis
      japonica to sulfide stress were investigated. The 24, 48, 72, and 96-h LC50
      values of Na2S were 6.634, 4.703, 3.886, and 2.190 mM, respectively. Based on
      these results, the crabs were exposed to 0.25, 0.50, 0.75, 1.00, and 1.25 mM of
      Na2S over a 15-day period, and sampled at 0, 1, 3, 5, 10, and 15 day for
      analyzing changes in immunity-related indicators in the hemolymph (including
      total hemocyte (THC), hemocyanin content, the activities of the phenoloxidase
      (PO), lysozyme (LSZ), superoxide dismutase (SOD) and catalase (CAT), and
      malondialdehyde (MDA) content), and the histological structures of major organs
      (gill, hepatopancreas, and stomach). The results showed that the activities of
      most immune-related factors declined after an initial rise under Na2S-induced
      stress, with the exception of MDA content that showed an overall increasing
      trend. After exposure to Na2S for 15 days, most of the measured indices were
      lower in treatment groups than in the control. Significant negative correlations
      was found between Na2S concentration and the activities of LSZ, SOD, CAT
      (p<0.01), while MDA content was found to be positively correlated with Na2S
      concentration (p<0.05). Noticeable changes in the histological structure of the
      main organs of C. japonica were observed upon exposure to high concentration of
      Na2S: the outer chitin layer of the gills became thin and partialy ruptured;
      hemocytes in the gill hemocoel were severely vacuolized; the morphology of
      glandular epithelium was irregular; the rough endoplasmic reticulum became
      swollen and reduced in number; and several large vacuoles and some residual
      bodies were observed in the gastric epithelium. These results indicate that
      stress induced by high concentration of sulfide can significantly affect the
      activities of immune-related enzymes and the organ structure of C. japonica.
      Furthermore, changes in the activities of LSZ, SOD, and CAT, and the content of
      MDA may be used as indices for evaluating the immune state of C. japonica under
      sulfide stress.

PMID- 24680751
TI  - Exposure to waterborne Cu inhibits cutaneous Na+ uptake in post-hatch larval
      rainbow trout (Oncorhynchus mykiss).
AB  - In freshwater rainbow trout (Oncorhynchus mykiss), two common responses to acute
      waterborne copper (Cu) exposure are reductions in ammonia excretion and Na(+)
      uptake at the gills, with the latter representing the likely lethal mechanism of
      action for Cu in adult fish. Larval fish, however, lack a functional gill
      following hatch and rely predominantly on cutaneous exchange, yet represent the
      most Cu-sensitive life stage. It is not known if Cu toxicity in larval fish
      occurs via the skin or gills. The present study utilized divided chambers to
      assess cutaneous and branchial Cu toxicity over larval development, using
      disruptions in ammonia excretion (Jamm) and Na(+) uptake (Jin(Na)) as
      toxicological endpoints. Early in development (early; 3 days post-hatch; dph),
      approximately 95% of Jamm and 78% of Jin(Na) occurred cutaneously, while in the
      late developmental stage (late; 25 dph), the gills were the dominant site of
      exchange (83 and 87% of Jamm and Jin(Na), respectively). Exposure to 50 MUg/l Cu
      led to a 49% inhibition of Jamm in the late developmental stage only, while in
      the early and middle developmental (mid; 17 dph) stages, Cu had no effect on
      Jamm. Jin(Na), however, was significantly inhibited by Cu exposure at the early
      (53% reduction) and late (47% reduction) stages. Inhibition at the early stage of
      development was mediated by a reduction in cutaneous uptake, representing the
      first evidence of cutaneous metal toxicity in an intact aquatic organism. The
      inhibitions of both Jamm and Jin(Na) in the late developmental stage occurred via
      a reduction in branchial exchange only. The differential responses of the skin
      and gills to Cu exposure suggest that the mechanisms of Jamm and Jin(Na) and/or
      Cu toxicity differ between these tissues. Exposure to 20MUg/l Cu revealed that
      Jamm is the more Cu-sensitive process. The results presented here have important
      implications in predicting metal toxicity in larval fish. The Biotic Ligand Model
      (BLM) is currently used to predict metal toxicity in aquatic organisms. However,
      for rainbow trout this is based on gill binding constants from juvenile fish.
      This may not be appropriate for post-hatch larval fish where the skin is the site
      of toxic action of Cu. Determining Cu binding constants and lethal accumulation
      concentrations for both skin and gills in larval fish may aid in developing a
      larval fish-specific BLM. Overall, the changing site of toxic action and
      physiology of developing larval fish present an interesting and exciting avenue
      for future research.

PMID- 24680752
TI  - Two-signal electrochemical method for evaluation suppression and proliferation of
      MCF-7 cells based on intracellular purine.
AB  - Two electrochemical signals ascribed to xanthine/guanine and hypanthine/adenine
      in MCF-7 cells were detected at 0.726 and 1.053 V, respectively. Based on the
      intensity of signals, the genistein-induced proliferation and suppression of MCF
      7 cells could be evaluated. The results showed that with the increase of
      genistein dose at the range of 10(-9) to 10(-6)M, the two electrochemical signals
      of MCF-7 cell suspension increased due to the proliferation, whereas the tendency
      at the high dosage range of more than 10(-5)M was decreased. The proliferation
      and cytotoxicity obtained by the electrochemical method were in agreement with
      those obtained by cell counting and the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium] method. Thus, the two-signal electrochemical method is an
      effective way to evaluate the effect of drugs on cell activity based on purine
      metabolism.

PMID- 24680753
TI  - Analysis of 3-O-sulfo group-containing heparin tetrasaccharides in heparin by
      liquid chromatography-mass spectrometry.
AB  - Complete heparin digestion with heparin lyase 2 affords a mixture of
      disaccharides and resistant tetrasaccharides with 3-O-sulfo group-containing
      glucosamine residues at their reducing ends. Quantitative online liquid
      chromatography-mass spectrometric analysis of these resistant tetrasaccharides is
      described in this article. The disaccharide and tetrasaccharide compositions of
      seven porcine intestinal heparins and five low-molecular-weight heparins were
      analyzed by this method. These resistant tetrasaccharides account for from 5.3 to
      7.3wt% of heparin and from 6.2 to 8.3wt% of low-molecular-weight heparin. Because
      these tetrasaccharides are derived from heparin's antithrombin III-binding sites,
      we examined whether this method could be applied to estimate the anticoagulant
      activity of heparin. The content of 3-O-sulfo group-containing tetrasaccharides
      in a heparin correlated positively (r=0.8294) to heparin's anticoagulant
      activity. 

PMID- 24680754
TI  - A new liquid chromatography/tandem mass spectrometry method for quantification of
      gangliosides in human plasma.
AB  - Gangliosides are a family of glycosphingolipids characterized by mono- or
      polysialic acid-containing oligosaccharides linked through 1,3- and 1,4-beta
      glycosidic bonds with subtle differences in structure that are abundantly present
      in the central nervous systems of many living organisms. Their cellular surface
      expression and physiological malfunction are believed to be pathologically
      implicated in considerable neurological disorders, including Alzheimer and
      Parkinson diseases. Recently, studies have tentatively elucidated that mental
      retardation or physical stagnation deteriorates as the physiological profile of
      gangliosides becomes progressively and distinctively abnormal during the
      development of these typical neurodegenerative syndromes. In this work, a reverse
      phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay using
      standard addition calibration for determination of GM2, GM3, GD2, and GD3 in
      human plasma has been developed and validated. The analytes and internal standard
      were extracted from human plasma using a simple protein precipitation procedure.
      Then the samples were analyzed by reverse-phase ultra-performance liquid
      chromatography (UPLC)/MS/MS interfaced to mass spectrometry with electrospray
      ionization using a multiple reaction monitoring mode to obtain superior
      sensitivity and specificity. This assay was validated for extraction recovery,
      calibration linearity, precision, and accuracy. Our quick and sensitive method
      can be applied to monitor ganglioside levels in plasma from normal people and
      neurodegenerative patients. 

PMID- 24680755
TI  - Acetylcholine modulates the immune response in Zhikong scallop Chlamys farreri.
AB  - Acetylcholine (ACh) is an indispensable neurotransmitter and neuromodulator in
      the cholinergic nervous system and it is implicated in the dynamic modulation of
      immune response in vertebrates. Although ACh has also been identified in most
      invertebrates, the knowledge about its immunomodulation is still limited. In the
      present study, the immunoreactivities of ACh and acetylcholinesterase (AChE) were
      observed in all the tested tissues of scallop Chlamys farreri, including adductor
      muscle, mantle, gill, hepatopancreas, kidney and gonad. The ACh concentration in
      the supernate of scallop hemolymph increased from 11.59 +/- 0.27 to 14.36 +/-
      0.17 MUM L(-1) at 6 h after LPS (0.5 mg ml(-1)) stimulation, and increased to
      15.51 +/- 1.20 MUM L(-1) at 3 h after the stimulation of tumor necrosis factor
      alpha (TNF-alpha) (50 ng ml(-1)). After LPS stimulation, the mRNA expression
      levels of superoxide dismutase (CfSOD), catalase (CfCAT) and lysozyme (CfLYZ) in
      hemocytes increased significantly at 3 h (P < 0.05), 6 h (P < 0.05) and 12 h (P <
      0.05), respectively. Compared with the LPS treatment, the induction of CfSOD,
      CfCAT and CfLYZ expression in hemocytes was repressed effectively (P < 0.05) by
      the co-stimulation of LPS and ACh (5 * 10(-7) M) at 3 h (P < 0.05), 6 h (P <
      0.05) and 12 h (P < 0.05), respectively. Furthermore, the expression level of
      CfCAT in hemocytes increased significantly after 12 h by the co-stimulation with
      LPS and ACh (P < 0.05). These results indicated collectively that the scallop
      cholinergic nervous system could be activated by immune stimulations, and it
      might play an essential role in immunomodulation of scallops.

PMID- 24680756
TI  - Perspectives on why digital ecologies matter: combining population genetics and
      ecologically informed agent-based models with GIS for managing dipteran livestock
      pests.
AB  - It is becoming clear that handling the inherent complexity found in ecological
      systems is an essential task for finding ways to control insect pests of tropical
      livestock such as tsetse flies, and old and new world screwworms. In particular,
      challenging multivalent management programs, such as Area Wide Integrated Pest
      Management (AW-IPM), face daunting problems of complexity at multiple spatial
      scales, ranging from landscape level processes to those of smaller scales such as
      the parasite loads of individual animals. Daunting temporal challenges also await
      resolution, such as matching management time frames to those found on ecological
      and even evolutionary temporal scales. How does one deal with representing
      processes with models that involve multiple spatial and temporal scales? Agent
      based models (ABM), combined with geographic information systems (GIS), may allow
      for understanding, predicting and managing pest control efforts in livestock
      pests. This paper argues that by incorporating digital ecologies in our
      management efforts clearer and more informed decisions can be made. I also point
      out the power of these models in making better predictions in order to anticipate
      the range of outcomes possible or likely. 

PMID- 24680757
TI  - Individuals with episodic amnesia are not stuck in time.
AB  - The metaphor that individuals with episodic amnesia due to hippocampal damage are
      "stuck in time" persists in science, philosophy, and everyday life despite
      mounting evidence that episodic amnesia can spare many central aspects of
      temporal consciousness. Here we describe some of this evidence, focusing
      specifically on KC, one of the most thoroughly documented and severe cases of
      episodic amnesia on record. KC understands the concept of time, knows that it
      passes, and can orient himself with respect to his personal past and future. He
      expresses typical attitudes toward his past and future, and he is able to make
      future-regarding decisions. Theories claiming that the hippocampus plays an
      essential role in temporal consciousness need to be revised in light of these
      findings. 

PMID- 24680758
TI  - Metabolic surgery for the treatment of hypertriglyceridemia-related pancreatitis
      due to familial lipoprotein lipase deficiency.

PMID- 24680759
TI  - Does the intragastric balloon have a predictive role in subsequent LAP-BAND((r))
      surgery? Italian multicenter study results at 5-year follow-up.
AB  - BACKGROUND: The intragastric balloon has been reported to be a safe and effective
      tool for temporary weight loss. The aim of this study is the evaluation of the
      possible predictive role of intragastric balloon when used before laparoscopic
      adjustable gastric banding. METHODS: A longitudinal multicenter study was
      conducted in patients with body mass index (BMI)>35 kg/m(2) who underwent gastric
      banding with the BioEnterics Intragastric Balloon (BIB). After balloon removal (6
      mo), patients were allocated into 2 group according to their percentage of excess
      weight loss (%EWL): group>25 (%EWL>25%) and group<25 (%EWL<25%). Patients from
      both group underwent laparoscopic adjustable gastric banding (LAGB) 1-3 months
      after BIB removal. The LAP-BAND AP band was placed in all patients via pars
      flaccida. Weight loss parameters were considered in both groups. RESULTS: From
      January 2005 to December 2009, 1357 patients were enrolled in this study. Mean
      BMI at time of BIB positioning was 44.9+/-8.4 (range 29-82.5). After 6 months, at
      time of removal, mean BMI was 39.4+/-7.3. According to the cutoff, patients were
      allocated into group A (n = 699) and group B (n = 658). At this time the mean BMI
      was 36.4+/-6.4 and 42.7+/-6.9 (P = .001) in groups A and B, respectively. At 1
      year follow-up from LAGB, mean BMI was 35.8+/-6.5 and 40.0+/-7.4 (P<.001) in
      groups A and B, respectively. This significant difference was confirmed at 3- and
      5-year follow-ups. A similar pattern was observed with the %EWL. CONCLUSION:
      Satisfactory results with BIB are predictive of a positive outcome of LASB at 1,
      3, and 5 years after the procedure, and poor results do not inevitably indicate a
      negative outcome for gastric banding.

PMID- 24680760
TI  - Hiatal hernia repair and gastroesophageal reflux disease in gastric banding
      patients: analysis of a national database.
AB  - BACKGROUND: Hiatal hernia (HH) is a risk factor for complications after
      laparoscopic adjustable gastric banding (LAGB), with recommendation to repair
      these at the time of LAGB placement. We reviewed the characteristics and outcomes
      of bariatric patients undergoing HH repair during LAGB. The aim of this study was
      to determine the prevalence of HH repair in LAGB patients and its potential
      effect on outcomes. METHODS: Using the Bariatric Outcomes Longitudinal Database,
      we identified patients who had hiatal hernia repair at the time of their LAGB
      (HHR group) and compared them to other LAGB patients without a HH repair (NonHHR
      group). RESULTS: Of 41,611 patients who underwent LAGB during 2007-2010, 8120
      (19.5%) had HH repair (HHR), adding only 4 minutes to the operating time, without
      an increase in blood transfusion, length of stay, or band-related complications.
      Preoperatively, the HHR cohort had a higher incidence of gastroesophageal reflux
      disease (GERD) compared with nonHHR (49% versus 40%, respectively; P<.001) with a
      higher GERD score (1.13 versus .88, respectively; P<.001). Of those with GERD,
      similar percentage of patients in the HHR and nonHHR groups experienced
      improvement 1-year after surgery (53% versus 52%, respectively, P = .4), with
      similar GERD scores at this time point. CONCLUSION: HH are repaired in one fifth
      of LAGB patients, with a surprisingly minimal increase in operative times and no
      change in length of stay, morbidity, or mortality. In patients with GERD, HH
      repair had minimal effect on postoperative improvements in reflux symptoms. These
      findings suggest that many of the repairs may involve small hernias with unclear
      clinical effect.

PMID- 24680761
TI  - Effect of perioperative management on short-term outcomes after sleeve
      gastrectomy: a 600-patient single-center cohort study.
AB  - BACKGROUND: Reports on the postoperative outcomes of sleeve gastrectomy (SG) have
      only been from small, single-center series and meta-analyses of studies with
      variable SG management. The objective of this study was to evaluate post-SG
      outcomes in a specialized bariatric surgery center with a routinely performed
      standardized procedure. METHODS: The postoperative complication rate, operating
      times, and postoperative data were evaluated from all patients undergoing a
      primary SG between November 2004 and February 2012. Results were analyzed for 3
      separate surgical periods, which differed with perioperative management. RESULTS:
      Of 600 patients (mean age: 41.8+/-11.3; mean body mass index [BMI]: 47.2+/-16
      kg/m2; 80% were women who underwent primary SG), 26.8% had a BMI>=50 kg/m2. The
      mean operating time was 84 minutes. The rate of conversion was 1%. There were no
      postoperative deaths. The overall complication rate was 8.5%; the major
      complication rate was 5.6%; the revisional surgery rate was 4.6% and the gastric
      leak rate was 2.5%. Over the course of the 3 study periods, the operating time
      fell from 91+/-32 to 79+/-22 minutes (P<=.001); the length of hospital stay
      decreased from 4.5+/-4.9 to 3.4+/-4.3 days (P = .02); the major complication rate
      fell from 6.4% to 5.5% (P = NS); and the gastric fistula rate decreased from 4.6%
      to 1.9% (P = NS). CONCLUSION: In a specialist bariatric surgery center, SG had an
      acceptable complication rate. Modifications in the perioperative management of SG
      were associated with a shorter mean operating time and hospital stay and did not
      increase the major complication or gastric fistula rates.

PMID- 24680762
TI  - High-risk alcohol use after weight loss surgery.
AB  - BACKGROUND: Bariatric or weight loss surgery (WLS) may alter alcohol metabolism
      resulting in a higher prevalence of problem drinking postoperatively. Few studies
      distinguish those who report improvements in drinking from those who report
      worsening behavior after surgery. The objective of this study was to characterize
      high-risk alcohol use before and after WLS and according to surgery type.
      METHODS: We interviewed patients before and annually after WLS. High-risk alcohol
      use as assessed via a modified version of the Alcohol Use Disorders
      Identification Test-Consumption. RESULTS: Of 541 participants who underwent WLS,
      375 (69% retention) completed the 1-year interview and 328 (63% retention)
      completed the 2-year interview. At 1 year, 13% reported high-risk drinking
      compared to 17% at baseline, P = .10; at year 2, 13% reported high-risk drinking
      compared to 15% at baseline, P = .39; 7% and 6% of patients, respectively,
      reported new high-risk drinking at 1- and 2-year follow-up. At both follow-up
      time points, more than half of those who reported high-risk drinking at baseline
      no longer did so. A larger proportion of gastric bypass patients (71%) reported
      amelioration in high-risk drinking than gastric banding (48%) at year 1, but this
      difference did not reach statistical significance (P = .07); the difference
      largely dissipated by year 2 (50% versus 57%) . CONCLUSION: Although 7% of
      patients report new high-risk alcohol use 1 year after WLS, more than half who
      reported high-risk alcohol use before surgery discontinued high-risk drinking.

PMID- 24680763
TI  - The role of endoscopic stents in the management of chronic anastomotic and staple
      line leaks and chronic strictures after bariatric surgery.
AB  - BACKGROUND: The use of endoluminal stents has been proposed for the management of
      fistulas and anastomotic strictures after bariatric surgery. The objective of our
      study was to determine the success of endoscopically placed, self-expandable
      metal stents (SEMS) in bariatric patients specifically with either chronic
      persistent anastomotic or staple line leaks/fistulas or chronic, persistent
      anastomotic strictures. METHODS: We treated 21 patients including 5 with chronic
      staple line leaks/fistulas (4 from the gastric sleeve after biliopancreatic
      diversion with duodenal switch [BPD/DS] and 1 after removal of an eroding
      laparoscopic adjustable gastric band) and 16 with chronic anastomotic strictures
      (15 at the gastrojejunostomy after Roux-en-Y gastric bypass and 1 at the
      duodenoileal anastomosis after BPD/DS). Patients with early leaks or anastomotic
      strictures were excluded. RESULTS: All but one of these patients had been
      referred to our institution after chronic treatment elsewhere was unsuccessful
      with prior stent placement for fistulas or multiple endoscopic dilations for
      strictures. Their bariatric operations had been performed a mean of 386 days
      beforehand. Stent placement was performed successfully in all patients without
      complications but was successful in only 4 of 21 patients (19%)-2 with chronic
      fistulas and 2 with chronic anastomotic strictures. Stent migration occurred in
      10 patients (47%); the migrated stents were removed/replaced endoscopically in 7
      patients but required elective operative removal in 3 with concomitant correction
      of the leak, fistula, or anastomotic stricture; none were operated emergently.
      CONCLUSION: Only 4 of 21 patients with a chronic persistent leak or anastomotic
      stricture were treated definitively using a SEMS. Although endoluminal stents may
      not lead to resolution of a chronic leak or stricture, SEMS may suppress ongoing
      sepsis and allow patients to undergo nutritional resuscitation orally before
      operative correction.

PMID- 24680764
TI  - A sensitive LC-MS/MS assay for brevisulcenal and brevisulcatic acid toxins
      produced by the dinoflagellate Karenia brevisulcata.
AB  - A toxic dinoflagellate, Karenia brevisulcata, devastated almost all marine life
      in Wellington Harbour, New Zealand during the late summer of 1998. Brevisulcatic
      acids (BSXs) and brevisulcenals (KBTs), both polycyclic ether toxins, have been
      identified as the causative agents. A liquid chromatography tandem mass
      spectrometry (LC-MS/MS) method has been developed and validated for the sensitive
      and specific determination of BSXs and KBTs in culture medium, seawater and
      shellfish. Acidified algal culture, or seawater, was extracted using reverse
      phase solid phase extraction cartridges. Shellfish tissue homogenate was blended
      with methanol-water (9:1) and partitioned with hexane to remove non-polar lipids.
      This extraction protocol is similar to that used for analysis of lipophilic
      shellfish toxins. LC-MS/MS (triple quadrupole) was used for quantitative analysis
      with gradient elution (acidic buffer), positive electrospray ionization and
      multiple-reaction monitoring. Purified toxins were available for 4 KBTs (KBT-F, 
      G, -H and -I) and 4 BSXs (-1, -2, -4, and -5), and were used to calibrate the
      instrument responses. Relative response factors were used for semi-quantitative
      analysis of BSX-3 and BSX-6, using BSX-1 and BSX-4 respectively. Calibration
      curves for all toxins monitored were linear over the concentration range tested
      (5-200 ng mL(-1)) with r(2) values >0.99. The method limit of quantitation was
      determined to be 2 ng mL(-1) for BSXs and KBTs, except KBT-I, which was 5 ng mL(
      1). Validation data was generated for culture medium and shellfish. Toxin
      recoveries were typically >70% with relative standard deviations <20% across all
      of the matrices tested. In addition, toxins specific to K. brevisulcata were able
      to be detected in seawater at a cell concentration of 10,000 cells L(-1), which
      represents the suggested trigger level for this harmful algal species. This
      method shows suitable performance characteristics to be regarded a useful tool to
      monitor toxin levels in a variety of sample matrices during future bloom events. 

PMID- 24680765
TI  - Appraisal of snakebite incidence and mortality in Bolivia.
AB  - No information has been yet published on snakebite in Bolivia. The country
      includes very different ecological situations leading to various epidemiological
      risks. A study has been carried out to evaluate the incidence and location of
      snakebite, particularly in relation with altitude, in order to improve
      management. Investigations on snakebite epidemiology were based on a) cases
      treated in health facilities as reported by health authorities and b) household
      surveys carried out in areas with high variations of altitude, in various regions
      of Bolivia. An average of 700 bites was treated each year in Bolivia (national
      annual incidence = 8 bites per 100,000 people) with a great disparity between
      districts. Household surveys showed annual incidences ranged from 30 to 110 bites
      per 100,000 inhabitants depending on location. Annual mortality ranged 0.1-3.9
      per 100,000 people. A significant and constant inverse correlation was shown
      between snakebite incidence and altitude, which may be explained by both snake
      and human distributions and activities. Notification of snakebite is useful for
      improving patient management and informing antivenom distribution. It should also
      involve the report of deaths and clinical details of envenomation. 

PMID- 24680766
TI  - In vitro investigation of toxicological interactions between the fusariotoxins
      deoxynivalenol and zearalenone.
AB  - It is expected that humans are exposed to combined mycotoxins, which occur
      simultaneously in the food items, than to individual compounds and that can
      increase their potential toxicity. Considering this coincident production,
      deoxynivalenol (DON) and zearalenone (ZEN) as they are produced by several
      Fusarium species, can interfere at a cellular level. Therefore, these two toxins
      were chosen to study their interactive effects on human colon carcinoma cells
      (HCT116), using the endpoints including cell viability, cell cycle analysis,
      mitochondrial transmembrane potential (DeltaPsim) determination and permeability
      transition pore (PTP) opening. Our results showed that DON and ZEN caused a
      marked decrease of cell viability in a dose-dependent manner, mediated by an
      activation of the mitochondrial apoptotic process; characterized by PTP opening
      and the loss of DeltaPsim. Nevertheless, combined DON and ZEN reduced all the
      toxicities observed with the mycotoxins separately. Therefore, the combination of
      the two mycotoxins appears as a sub-additive response. 

PMID- 24680767
TI  - Implications of retinal effects observed in chronic toxicity studies on the
      clinical development of a CNS-active drug candidate.
AB  - The development path described for JNJ-26489112 provides perspectives on
      interpretation of retinal effects observed in nonclinical studies and their
      implications for clinical development. JNJ-26489112 is a CNS-active
      investigational drug that has potential as a novel treatment for treatment
      resistant and bipolar depression, epilepsy, and neuropathic/inflammatory pain. In
      a 6-month toxicity study in albino rats, retinal atrophy was observed at
      supratherapeutic exposures to JNJ-26489112. The histopathological changes and
      topography of the lesions were characteristic of light-induced damage specific to
      albino rats. The species/strain specificity is supported by an absence of any
      ocular effects in dogs and in pigmented and albino rats, housed under standard
      and reduced lighting, respectively. To further evaluate its potential to cause
      ocular effects, in vivo functional and structural ocular analyses were included
      in a 9-month monkey toxicity study. Reductions in rod- and cone-mediated
      electroretinograms were observed at supratherapeutic exposures but without any
      histopathologic changes. These data suggested that the effects of JNJ-26489112 in
      monkeys were neuromodulatory and not neurotoxic. Taken together, data related to
      the light-induced atrophy in albino rats and reversible neuromodulatory effects
      in monkeys, supported the safe evaluation of JNJ-26489112 in a clinical proof-of
      concept study that included comprehensive functional and structural ocular
      monitoring. 

PMID- 24680768
TI  - Assessment of tacrolimus absorption from the human intestinal tract: open-label,
      randomized, 4-way crossover study.
AB  - BACKGROUND: Tacrolimus is an established immunosuppressant used for the
      prevention and treatment of allograft rejection in solid organ transplantation.
      An immediate-release oral formulation of tacrolimus has been commercially
      available since 1994 that is administered orally BID. To improve the compliance
      and quality of life of transplant patients, a once-daily modified release (MR)
      formulation is an attractive option. However, to be successful, the drug of
      interest must be sufficiently well absorbed from the distal region of the
      gastrointestinal tract. OBJECTIVE: To facilitate the development of an MR
      formulation, we investigated the absorption of tacrolimus from different regions
      of the human gastrointestinal tract, proximal and distal small bowels, and
      ascending colon. METHODS: The study was performed as an open-label, randomized, 4
      way crossover design in 6 healthy white male subjects. For each subject, 1 mg (2
      mg/mL) of tacrolimus solution in polyethylene glycol 400 was administered to each
      location in the gastrointestinal tract via a site-specific radiolabeled delivery
      capsule, which can release tacrolimus solution at specific sites of the
      gastrointestinal tract. Real-time visualization of capsule location and
      tacrolimus release at each target site was performed by using gamma-scintigraphy.
      Blood samples were collected to determine tacrolimus levels in the blood. The
      pharmacokinetic parameters Cmax, Tmax after the capsule activation, AUC0-24, and
      mean residence time were determined from the concentration-time profiles.
      RESULTS: Ten healthy male subjects underwent dosing. Six subjects completed all 4
      treatments. Three adverse events (mild headache [n = 1], small amount of blood in
      stool [n = 1], and mild syncopal episode [n = 1]) that were possibly study drug
      related were reported in 3 different subjects. Tacrolimus was absorbed from not
      only the small intestine but also from the colonic region of the gastrointestinal
      tract. Although AUC0-24 values revealed some site-specific absorption tendencies,
      the mean AUC0-24 values obtained were similar regardless of the location of
      tacrolimus release from the capsule. CONCLUSIONS: Tacrolimus was absorbed from
      the duodenum to the colon in these male subjects, although differences were
      observed in the value of AUC0-24, possibly due to variation in cytochrome P450
      3A4 activity in the intestine. Although this study was conducted in small group
      of healthy fasting men, the present results indicate that tacrolimus is suitable
      for MR formulation development due to a wide absorption window throughout the
      intestine in humans.

PMID- 24680769
TI  - MiR-378 as a biomarker for response to anti-angiogenic treatment in ovarian
      cancer.
AB  - OBJECTIVE: To determine the role of miR-378 as a biomarker for anti-angiogenic
      therapy response in ovarian cancer. METHODS: Expression of miR-378 was analyzed
      in ovarian cancer cell lines and human tumors vs. normal ovarian epithelial cells
      by qRT-PCR. After miR-378 transfection in SKOV3 cells, dysregulated genes were
      identified using microarray. Data from The Cancer Genome Atlas (TCGA) was
      utilized to correlate miR-378 expression with progression-free survival (PFS)
      among patients treated with anti-angiogenic therapy by using Kaplan-Meier and Cox
      proportional hazards. RESULTS: MiR-378 was overexpressed in ovarian cancer cells
      and tumors vs. normal ovarian epithelial cells. Overexpressing miR-378 in ovarian
      cancer cells altered expression of genes associated with angiogenesis (ALCAM,
      EHD1, ELK3, TLN1), apoptosis (RPN2, HIPK3), and cell cycle regulation (SWAP-70,
      LSM14A, RDX). In the TCGA dataset, low vs. high miR-378 expression was associated
      with longer PFS in a subset of patients with recurrent ovarian cancer treated
      with bevacizumab (9.2 vs. 4.2months; p=0.04). On multivariate analysis, miR-378
      expression was an independent predictor for PFS after anti-angiogenic treatment
      (HR=2.04, 95% CI: 1.12-3.72; p=0.02). Furthermore, expression levels of two miR
      378 targets (ALCAM and EHD1) were associated with PFS in this subgroup of
      patients who received anti-angiogenic therapy (9.4 vs. 4.2months, p=0.04 for high
      vs. low ALCAM; 7.9 vs. 2.3months, p<0.01 for low vs. high EHD1). CONCLUSIONS: Our
      data suggest that miR-378 is overexpressed in ovarian cancer cells and tumors vs.
      normal ovarian epithelial cells. MiR-378 and its downstream targets may serve as
      markers for response to anti-angiogenic therapy.

PMID- 24680770
TI  - Spatial analysis of adherence to treatment guidelines for advanced-stage ovarian
      cancer and the impact of race and socioeconomic status.
AB  - OBJECTIVE: To determine the impact of geographic location on advanced-stage
      ovarian cancer care adherence to the National Comprehensive Cancer Network (NCCN)
      guidelines in relation to race and socioeconomic status (SES). METHODS: Patients
      diagnosed with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were
      identified from the California Cancer Registry. Generalized additive models were
      created to assess the effect of spatial distributions of geographic location,
      proximity to a high-volume hospital (>=20 cases/year), distance traveled to
      receive care, race, and SES on adherence to NCCN guidelines, with simultaneous
      smoothing of geographic location and adjustment for confounding variables.
      Disparities in geographic predictors of treatment adherence were analyzed with
      the x(2) test for equality of proportions. RESULTS: Of the 11,770 patients
      identified, 45.4% were treated according to NCCN guidelines. Black race (OR=1.49,
      95%CI=1.21-1.83), low-SES (OR=1.46, 95%CI=1.24-1.72), and geographic location
      >=80 km/50 mi from a high-volume hospital (OR=1.88, 95%CI=1.61-2.19) were
      independently associated with an increased risk of non-adherent care, while high
      volume hospital treatment (OR=0.59, 95%CI=0.53-0.66) and travel distance to
      receive care >=32 km/20 mi (OR=0.80, 95%CI=0.69-0.92) were independently
      protective. SES was inversely associated with location >=80 km/50 mi from a high
      volume hospital, ranging from 6.3% (high-SES) to 33.0% (low-SES) (p<0.0001).
      White patients were significantly more likely to travel >=32 km/20 mi to receive
      care (21.8%) compared to Blacks (14.4%), Hispanics (15.9%), and Asian/Pacific
      Islanders (15.5%) (p<0.0001). CONCLUSION: Geographic proximity to a high-volume
      hospital and travel distance to receive treatment are independently associated
      with NCCN guideline adherent care for advanced-stage ovarian cancer. Geographic
      barriers to standard ovarian cancer treatment disproportionately affect racial
      minorities and women of low-SES.

PMID- 24680772
TI  - Reading with peripheral vision: a comparison of reading dynamic scrolling and
      static text with a simulated central scotoma.
AB  - Horizontally scrolling text is, in theory, ideally suited to enhance viewing
      strategies recommended to improve reading performance under conditions of central
      vision loss such as macular disease, although it is largely unproven in this
      regard. This study investigated if the use of scrolling text produced an
      observable improvement in reading performed under conditions of eccentric viewing
      in an artificial scotoma paradigm. Participants (n=17) read scrolling and static
      text with a central artificial scotoma controlled by an eye-tracker. There was an
      improvement in measures of reading accuracy, and adherence to eccentric viewing
      strategies with scrolling, compared to static, text. These findings illustrate
      the potential benefits of scrolling text as a potential reading aid for those
      with central vision loss. 

PMID- 24680771
TI  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and
      proteolytic processing by a disintegrin and metalloproteinases (ADAM): a
      regulator of several pathways.
AB  - HB-EGF is a member of the EGF family of ligands that is initially synthesized as
      a membrane-bound growth factor termed, proHB-EGF. The membrane bound proHB-EGF
      undergoes extensive proteolytic processing by several metalloproteinases capable
      of stimulating cellular proliferation. Soluble, mature HB-EGF binds to and
      activates EGF receptors. HB-EGF is a critical molecular component to a number of
      normal physiological processes including but not limited to tissue injury and
      wound healing, reproduction, angiogenesis and recently, adipogenesis.
      Misexpression of HB-EGF is linked to tumor formation and cancer including
      hepatocellular, pancreatic, gastric, breast, colon and melanoma, gliomas and
      glioblastomas. HB-EGF is a likely tool for therapeutic approaches to enhance
      treatment of injuries as well as a target for prevention of several cancers and
      obesity. 

PMID- 24680773
TI  - Sp1 transcriptionally regulates BRK1 expression in non-small cell lung cancer
      cells.
AB  - Following a previous study reporting that BRK1 is upregulated in non-small cell
      lung cancer (NSCLC), the present study sought to clarify the role of specificity
      protein 1 (Sp1) in the transcriptional regulation of the BRK1 gene. Therefore, a
      construct, named F8, consisting of the -1341 to -1 nt sequence upstream of the
      start codon of the BRK1 gene inserted into pGL4.26 was made. A series of
      truncated fragments was then constructed based on F8. Segment S831, which
      contained the -84 to -1 nt region, displayed the highest transcriptional activity
      in the A549, H1299 and H520 NSCLC cell lines. Bioinformatic analysis showed a
      potential Sp1-binding element at -73 to -64 nt, and a mutation in this region
      suppressed the transcriptional activity of S831. Then the RNAi assays of Sp1 and
      its coworkers Sp3 and Sp4 were performed, and suppression of Sp1 by siRNA
      inhibited the mRNA expression of BRK1. Both an electrophoretic mobility shift
      assay (EMSA) and a chromatin immunoprecipitation (ChIP) assay demonstrated that
      Sp1 bound to the promoter area of the BRK1 gene. Our data identified a functional
      and positive Sp1 regulatory element from -73 to -64 nt in the BRK1 promoter,
      which may likely explain the overexpression of BRK1 in NSCLC.

PMID- 24680774
TI  - Insight into genetic determinants of resting heart rate.
AB  - BACKGROUND: Recent studies suggested that resting heart rate (RHR) might be an
      independent predictor of cardiovascular mortality and morbidity. Nonetheless, the
      interrelation between RHR and cardiovascular diseases is not clear. In order to
      resolve this puzzle, the importance of genetic determinants of RHR has been
      recently suggested, but it needs to be further investigated. OBJECTIVE: The aim
      of this study was to estimate the contribution of common genetic variations on
      RHR using Genome Wide Association Study. METHODS: We performed a Genome Wide
      Association Study in an isolated population cohort of 1737 individuals, the
      Italian Network on Genetic Isolates - Friuli Venezia Giulia (INGI-FVG). Moreover,
      a haplotype analysis was performed. A regression tree analysis was run to
      highlight the effect of each haplotype combination on the phenotype. RESULTS: A
      significant level of association (p<5 * 10(-8)) was detected for Single
      Nucleotide Polymorphisms (SNPs) in two genes expressed in the heart: MAML1 and
      CANX. Founding that the three different variants of the haplotype, which
      encompass both genes, yielded a phenotypic correlation. Indeed, a haplotype in
      homozygosity is significantly associated with the lower quartile of RHR (RHR <=
      58 bpm). Moreover no significant association was found between cardiovascular
      risk factors and the different haplotype combinations. CONCLUSION: Mastermind
      like 1 and Calnexin were found to be associated with RHR. We demonstrated a
      relation between a haplotype and the lower quartile of RHR in our populations.
      Our findings highlight that genetic determinants of RHR may be implicated in
      determining cardiovascular diseases and could allow a better risk stratification.

PMID- 24680775
TI  - Mitogenomic circumscription of a novel percomorph fish clade mainly comprising
      "Syngnathoidei" (Teleostei).
AB  - Percomorpha, comprising about 60% of modern teleost fishes, has been described as
      the "(unresolved) bush at the top" of the tree, with its intrarelationships still
      being ambiguous owing to huge diversity (>15,000 species). Recent molecular
      phylogenetic studies based on extensive taxon and character sampling, however,
      have revealed a number of unexpected clades of Percomorpha, and one of which is
      composed of Syngnathoidei (seahorses, pipefishes, and their relatives) plus
      several groups distributed across three different orders. To circumscribe the
      clade more definitely, we sampled several candidate taxa with reference to the
      previous studies and newly determined whole mitochondrial genome (mitogenome)
      sequences for 16 percomorph species across syngnathoids, dactylopterids, and
      their putatively closely-related fishes (Mullidae, Callionymoidei,
      Malacanthidae). Unambiguously aligned sequences (13,872 bp) from those 16 species
      plus 78 percomorphs and two outgroups (total 96 species) were subjected to
      partitioned Bayesian and maximum likelihood analyses. The resulting trees
      revealed a highly supported clade comprising seven families in Syngnathoidei
      (Gasterosteiformes), Dactylopteridae (Scorpaeniformes), Mullidae in Percoidei and
      two families in Callionymoidei (Perciformes). We herein proposed to call this
      clade "Syngnathiformes" following the latest nuclear DNA studies with some
      revisions on the included families.

PMID- 24680776
TI  - High expression of heat shock protein 90 alpha and its significance in human
      acute leukemia cells.
AB  - This study investigated the expression of heat shock protein 90 alpha
      (Hsp90alpha) in acute leukemia cells. The expression of Hsp90alpha was
      investigated in leukemia cell lines and human bone marrow mononuclear cells
      derived from acute leukemia patients and from healthy individuals using
      polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay.
      Compared with cells from healthy individuals, the expression of Hsp90alpha in the
      untreated patients was higher. Similarly high levels were observed in remission
      patients. Significantly higher expression levels were observed in all the tested
      cell lines, and in cells from refractory and relapsed patients. No obvious
      relationship was observed between the occurrence of graft versus host disease and
      the expression of Hsp90alpha. The untreated patients showing higher expression
      levels of Hsp90alpha had lower complete remission rates. During remission of
      untreated patients, the expression of Hsp90alpha decreased and reached the lowest
      level after transplantation, but the expression increased again before relapse.
      Hsp90alpha was highly expressed in leukemia cells. The expression level of
      Hsp90alpha was associated with leukemia prognosis. However, no obvious
      relationship was observed between the occurrence of graft versus host disease and
      the expression of Hsp90alpha.

PMID- 24680777
TI  - Progranulin polymorphism rs5848 is associated with increased risk of Alzheimer's
      disease.
AB  - Progranulin is the precursor of granulins, and its down-regulation leads to
      neurodegeneration. Recent studies have indicated an association of progranulin
      polymorphism rs5848 with Alzheimer's disease (AD) risk, but the results remain
      controversial. To verify the association between rs5848 and AD risk, we retrieved
      the published literature from PubMed and other databases, and performed a meta
      analysis by pooling all five studies containing 2502 AD cases and 2162 controls.
      The results showed that rs5848 is associated with increased risk of AD in
      homozygous (TT vs. CC: OR, 1.36; 95% CI, 1.11-1.66; P=0.003) and recessive models
      (TT vs. CC+CT: OR, 1.31; 95% CI, 1.08-1.58; P=0.006). This association was
      remained in Caucasian (2227 cases and 1902 controls). Our data indicate that TT
      allele of rs5848 is associated with increased risk of AD, suggesting that genetic
      variant of progranulin gene may play an important role in AD development. 

PMID- 24680778
TI  - Association of VDR-gene variants with factors related to the metabolic syndrome,
      type 2 diabetes and vitamin D deficiency.
AB  - The prevalence of metabolic syndrome (MetS) is rising alarmingly in the Saudi
      Arabian population. This study was conducted to assess the association between
      vitamin D receptor (VDR) polymorphisms and genetic susceptibility to components
      of the metabolic syndrome, type 2 diabetes mellitus (T2DM), and vitamin D
      deficiency in the Saudi Arabian population. Five-hundred-seventy Saudi
      individuals (285 MetS and 285 controls) were enrolled in this cross-sectional
      study. TaqI, BsmI, ApaI and FokI single nucleotide polymorphisms (SNPs) of the
      VDR gene were genotyped. The CT genotype and allele T of BsmI were associated
      with lower HDL-C levels [OR 0.60 (0.37, 0.96), p=0.03] and obesity [OR 1.4 (1.0,
      1.90), p=0.04], respectively. The CT genotype and the dominant model CT+TT of
      BsmI were associated with increased risk of diabetes [OR 1.7 (1.2, 2.4),
      p=0.007], and [OR 1.5 (1.1, 2.2), p=0.01], respectively. On the contrary, the CT
      and CT+CC genotypes of FokI exhibited an association with a reduced risk of
      diabetes [OR 0.70 (0.49, 0.99), p=0.05] and [OR 0.67 (0.48, 0.94), p=0.02],
      respectively. The allele C of FokI was associated with lower risk of developing
      T2DM [OR 0.73 (0.56, 0.95), p=0.02]. The prevalence of vitamin D deficiency was
      lower in subjects with the AC genotype of ApaI [OR, 0.34 (0.14, 0.80), p=0.01].
      Components of the MetS such as obesity, low HDL and T2DM were associated with the
      VDR gene. FokI and BsmI have protective and facilitative effects on the risk for
      T2DM, while the ApaI genotype was associated with reduced vitamin D deficiency.

PMID- 24680780
TI  - Morpho-molecular analysis as a prognostic model for repulsive feedback of the
      medicinal plant "Andrographis paniculata" to allogamy.
AB  - Andrographis paniculata Nees. (AP) is a self-pollinated medicinal herb with a
      wide range of pharmaceutical properties, facing a low diversity in Malaysia.
      Cross-pollination of AP accessions leads to considerable rates of heterosis in
      the agro-morphological characteristics and anticancer phytochemicals of this
      eminent medicinal herb. However, the poor crossability of the plant at the
      interpopulation or intraspecific levels is an obstacle from the evolutionary and
      breeding points of view as an average of 4.56% crossability was recorded for AP
      in this study. Hence, this research aimed to elicit the impact of parental
      genetic distances (GDs) on the rate of crossability of AP using seven accessions
      in 21 possible cross combinations. To this end, a set of 55 randomly amplified
      polymorphic DNA (RAPD) primers and a total of 13 agro-morphological markers were
      employed to test the hypothesis. Twenty-two out of the 55 RAPD primers amplified
      a total of 257 bands of which 107 bands were found to be polymorphic. The
      principal component analysis (PCA) based on the RAPD markers revealed that the
      studied AP accessions were distributed to three distinct groups. Furthermore, it
      was noticed that even a minor increase in GD between two parents can cause a
      decline in their crossability. Unlike, the morphological-based GDs acted
      neutrally to crossability. This finding suggests that, despite the low genetic
      diversity among the Malaysian APs, a population prescreening using RAPD markers
      would be useful to enhance the rate of fruit set through selecting the
      genetically adjacent parents.

PMID- 24680779
TI  - Genetic polymorphisms of IFNG and IFNGR1 in association with the risk of
      pulmonary tuberculosis.
AB  - OBJECTIVE: Genetic host factors play an important role in controlling
      individual's susceptibility to the pathogen. This study aims to explore the
      single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and
      its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese
      Han population. METHODS: This population-based case control study consisted of
      1434 pulmonary tuberculosis patients and 1412 healthy controls. Six tag SNPs in
      IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The
      logistic regression model was carried out to analyze the associations between the
      genotypes and haplotypes and the risk of tuberculosis by calculating the odds
      ratio (OR) and 95% confidence interval (CI). RESULTS: After the Bonferroni
      correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and
      rs7749390) in IFNGR1 gene were observed to be significantly associated with the
      altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C
      allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76
      0.91). The additive model revealed that each additional allele contributed about
      14% decreased risk (OR: 0.86, 95% CI: 0.77-0.95). Moreover, we observed a strong
      linkage disequilibrium between rs2234711 and rs3799488. Compared with the common
      rs2234711C-rs3799488C haplotype, the haplotype rs2234711T-rs3799488C contributed
      to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI:
      1.09-1.41). CONCLUSIONS: Our results suggest that genetic polymorphisms in IFNGR1
      gene are involved in the risk of tuberculosis in the Chinese population. Future
      studies should include a comprehensive sequencing analysis to identify the
      specific causative sequence variants underlying the observed associations.

PMID- 24680781
TI  - Identification of Tf1 integration events in S. pombe under nonselective
      conditions.
AB  - Integration of retroviral elements into the host genome is a phenomena observed
      among many classes of retroviruses. Much information concerning the integration
      of retroviral elements has been documented based on in vitro analysis or
      expression of selectable markers. To identify possible Tf1 integration events
      within silent regions of the Schizosaccharomyces pombe genome, we focused on
      performing an in vivo genome-wide analysis of Tf1 integration events from the
      nonselective phase of the retrotransposition assay. We analyzed 1000 individual
      colonies streaked from four independent Tf1 transposed patches under nonselection
      conditions. Our analysis detected a population of G418(S)/neo(+) Tf1 integration
      events that would have been overlooked during the selective phase of the assay.
      Further RNA analysis from the G418(S)/neo(+) clones revealed 50% of clones
      expressing the neo selectable marker. Our data reveals Tf1's ability to insert
      within silent regions of S. pombe's genome.

PMID- 24680783
TI  - 2dx_automator: implementation of a semiautomatic high-throughput high-resolution
      cryo-electron crystallography pipeline.
AB  - The introduction of direct electron detectors (DED) to cryo-electron microscopy
      has tremendously increased the signal-to-noise ratio (SNR) and quality of the
      recorded images. We discuss the optimal use of DEDs for cryo-electron
      crystallography, introduce a new automatic image processing pipeline, and
      demonstrate the vast improvement in the resolution achieved by the use of both
      together, especially for highly tilted samples. The new processing pipeline (now
      included in the software package 2dx) exploits the high SNR and frame readout
      frequency of DEDs to automatically correct for beam-induced sample movement, and
      reliably processes individual crystal images without human interaction as data
      are being acquired. A new graphical user interface (GUI) condenses all
      information required for quality assessment in one window, allowing the imaging
      conditions to be verified and adjusted during the data collection session. With
      this new pipeline an automatically generated unit cell projection map of each
      recorded 2D crystal is available less than 5 min after the image was recorded.
      The entire processing procedure yielded a three-dimensional reconstruction of the
      2D-crystallized ion-channel membrane protein MloK1 with a much-improved
      resolution of 5A in-plane and 7A in the z-direction, within 2 days of data
      acquisition and simultaneous processing. The results obtained are superior to
      those delivered by conventional photographic film-based methodology of the same
      sample, and demonstrate the importance of drift-correction.

PMID- 24680782
TI  - Atomistic insights into human Cys-loop receptors by solution NMR.
AB  - Cys-loop receptors are pentameric ligand-gated ion channels (pLGICs) mediating
      fast neurotransmission in the central and peripheral nervous systems. They are
      important targets for many currently used clinical drugs, such as general
      anesthetics, and for allosteric modulators with potential therapeutic
      applications. Here, we provide an overview of advances in the use of solution NMR
      in structural and dynamic characterization of ion channels, particularly human
      Cys-loop receptors. We present challenges to overcome and realistic solutions for
      achieving high-resolution structural information for this family of receptors. We
      discuss how subtle structural differences among homologous channels define unique
      channel pharmacological properties and advocate the necessity to determine high
      resolution structures for individual receptor subtypes. Finally, we describe drug
      binding to the TMDs of Cys-loop receptors identified by solution NMR and the
      associated dynamics changes relevant to channel functions.

PMID- 24680784
TI  - A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic
      dynein.
AB  - Dyneins are large protein complexes that act as microtubule based molecular
      motors. The dynein heavy chain contains a motor domain which is a member of the
      AAA+ protein family (ATPases Associated with diverse cellular Activities).
      Proteins of the AAA+ family show a diverse range of functionalities, but share a
      related core AAA+ domain, which often assembles into hexameric rings. Dynein is
      unusual because it has all six AAA+ domains linked together, in one long
      polypeptide. The dynein motor domain generates movement by coupling ATP driven
      conformational changes in the AAA+ ring to the swing of a motile element called
      the linker. Dynein binds to its microtubule track via a long antiparallel coiled
      coil stalk that emanates from the AAA+ ring. Recently the first high resolution
      structures of the dynein motor domain were published. Here we provide a detailed
      structural analysis of the six AAA+ domains using our Saccharomycescerevisiae
      crystal structure. We describe how structural similarities in the dynein AAA+
      domains suggest they share a common evolutionary origin. We analyse how the
      different AAA+ domains have diverged from each other. We discuss how this is
      related to the function of dynein as a motor protein and how the AAA+ domains of
      dynein compare to those of other AAA+ proteins. 

PMID- 24680785
TI  - Axial helix rotation as a mechanism for signal regulation inferred from the
      crystallographic analysis of the E. coli serine chemoreceptor.
AB  - Bacterial chemotaxis receptors are elongated homodimeric coiled-coil bundles,
      which transduce signals generated in an N-terminal sensor domain across 15-20nm
      to a conserved C-terminal signaling subdomain. This signal transduction regulates
      the activity of associated kinases, altering the behavior of the flagellar motor
      and hence cell motility. Signaling is in turn modulated by selective methylation
      and demethylation of specific glutamate and glutamine residues in an adaptation
      subdomain. We have determined the structure of a chimeric protein, consisting of
      the HAMP domain from Archaeoglobus fulgidus Af1503 and the methyl-accepting
      domain of Escherichia coli Tsr. It shows a 21nm coiled coil that alternates
      between two coiled-coil packing modes: canonical knobs-into-holes and
      complementary x-da, a variant form related to the canonical one by axial rotation
      of the helices. Comparison of the obtained structure to the Thermotoga maritima
      chemoreceptor TM1143 reveals that they adopt different axial rotation states in
      their adaptation subdomains. This conformational change is presumably induced by
      the upstream HAMP domain and may modulate the affinity of the chemoreceptor to
      the methylation-demethylation system. The presented findings extend the cogwheel
      model for signal transmission to chemoreceptors. 

PMID- 24680786
TI  - McLean et al.'s paper, ''Incidence and predictors of neck and widespread pain
      after motor vehicle collision among U.S. litigants and nonlitigants''.

PMID- 24680787
TI  - Suppression of the auditory N1-component for heartbeat-related sounds reflects
      interoceptive predictive coding.
AB  - Although many studies have elucidated the neurocognitive mechanisms supporting
      the processing of externally generated sensory signals, less is known about the
      processing of interoceptive signals related to the viscera. Drawing a parallel
      with research on agency and the perception of self-generated action effects, in
      the present EEG study we report a reduced auditory N1 component when participants
      listened to heartbeat-related sounds compared to externally generated sounds. The
      auditory suppression for heartbeat sounds was robust and persisted after
      controlling for ECG-related artifacts, the number of trials involved and the
      phase of the cardiac cycle. In addition, the auditory N1 suppression for
      heartbeat-related sounds had a comparable scalp distribution as the N1
      suppression observed for actively generated sounds. This finding indicates that
      the brain automatically differentiates between heartbeat-related and externally
      generated sounds through a process of sensory suppression, suggesting that a
      comparable predictive mechanism may underlie the processing of heartbeat and
      action-related information. Extending recent behavioral data about cardio-visual
      integration, the present cardio-auditory EEG data reveal that the processing of
      sounds in auditory cortex is systematically modulated by an interoceptive cardiac
      signal. The findings are discussed with respect to theories of interoceptive
      awareness, emotion, predictive coding, and their relevance to bodily self
      consciousness. 

PMID- 24680788
TI  - Treatment of depression in a patient with epilepsy.

PMID- 24680789
TI  - A model of TMS-induced I-waves in motor cortex.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) allows to manipulate neural
      activity non-invasively, and much research is trying to exploit this ability in
      clinical and basic research settings. In a standard TMS paradigm, single-pulse
      stimulation over motor cortex produces repetitive responses in descending motor
      pathways called I-waves. However, the details of how TMS induces neural activity
      patterns in cortical circuits to produce these responses remain poorly
      understood. According to a traditional view, I-waves are due to repetitive
      synaptic inputs to pyramidal neurons in layer 5 (L5) of motor cortex, but the
      potential origin of such repetitive inputs is unclear. OBJECTIVE/HYPOTHESIS: Here
      we aim to test the plausibility of an alternative mechanism behind D- and I-wave
      generation through computational modeling. This mechanism relies on the broad
      distribution of conduction delays of synaptic inputs arriving at different parts
      of L5 cells' dendritic trees and their spike generation mechanism. METHODS: Our
      model consists of a detailed L5 pyramidal cell and a population of layer 2 and 3
      (L2/3) neurons projecting onto it with synapses exhibiting short-term depression.
      I-waves are simulated as superpositions of spike trains from a large population
      of L5 cells. RESULTS: Our model successfully reproduces all basic characteristics
      of I-waves observed in epidural responses during in vivo recordings of conscious
      humans. In addition, it shows how the complex morphology of L5 neurons might play
      an important role in the generation of I-waves. In the model, later I-waves are
      formed due to inputs to distal synapses, while earlier ones are driven by
      synapses closer to the soma. Finally, the model offers an explanation for the
      inhibition and facilitation effects in paired-pulse stimulation protocols.
      CONCLUSIONS: In contrast to previous models, which required either neural
      oscillators or chains of inhibitory interneurons acting upon L5 cells, our model
      is fully feed-forward without lateral connections or loops. It parsimoniously
      explains findings from a range of experiments and should be considered as a
      viable alternative explanation of the generating mechanism of I-waves.

PMID- 24680791
TI  - Addressing the disparity in physical health provision for people with
      schizophrenia: an important role for physiotherapists.

PMID- 24680790
TI  - Baseline serum 25-hydroxyvitamin d levels in men undergoing radical
      prostatectomy: is there an association with adverse pathologic features?
AB  - INTRODUCTION/BACKGROUND: The purpose of this study was to evaluate the prevalence
      of vitamin D (VitD) deficiency in men undergoing radical prostatectomy and
      determine whether an association exists between preoperative VitD levels and
      adverse pathologic features. PATIENTS AND METHODS: Patients scheduled to undergo
      radical prostatectomy for clinically localized disease from January to August
      2012 were prospectively followed and those with available preoperative serum 25
      hydroxyvitamin D levels were included. Men with a known diagnosis of VitD
      deficiency or taking VitD supplementation were excluded. Cox regression analysis
      was performed to determine whether preoperative VitD level is predictive of
      adverse pathologic outcomes. RESULTS: One hundred consecutive men were included.
      Mean age was 62 (range, 42-79) years and mean VitD level was 26 (range, 6-57)
      ng/mL. Overall, 65 men (65%) had suboptimal levels of VitD (< 30 ng/mL), and 32
      (32%) had deficiency (< 20 ng/mL). There was no significant correlation between
      VitD and age (P = .5). In logistic regression analysis, VitD level was not
      predictive of pathologic Gleason (P = .11), pathologic stage (P = .7), or
      positive margin status (P = .8). CONCLUSION: The association between VitD and
      prostate cancer has been controversial and data suggesting an increased risk of
      aggressive cancer in men with low levels of VitD have been inconsistent. We found
      that baseline preoperative VitD level was not associated with any adverse
      pathologic features. However, VitD deficiency is a common finding in this
      population, although unrelated to patient age. These results represent the first
      time the correlation between VitD and prostate cancer has been evaluated in a
      cohort of men undergoing radical prostatectomy.

PMID- 24680792
TI  - Movement and pain patterns in early stage primary/idiopathic adhesive capsulitis:
      a factor analysis.
AB  - OBJECTIVES: To evaluate patients clinically diagnosed with early stage
      primary/idiopathic adhesive capsulitis to determine the existence of any pattern
      of movement loss and associated pain that may facilitate early recognition.
      DESIGN: Cross-sectional study. SETTING: Private upper limb specialty clinic,
      Newcastle, Australia. PARTICIPANTS: Fifty-two patients clinically diagnosed with
      early stage adhesive capsulitis by a medical practitioner or physiotherapist.
      MAIN OUTCOME MEASURES: Percentage loss of active and passive ranges of eight
      shoulder movements and the pain level at the end of each movement. The reason for
      limitation of movement was also recorded. RESULTS: Factor analysis clearly
      identified two groups for percentage loss of active range of movement. Notably
      external rotation movements grouped separately from other movements. A single
      group emerged for percentage loss of passive range of movement suggesting a non
      specific global loss. For both pain at the end of active range of movement and
      passive range of movement two groups emerged, however the delineation between the
      groups was less clear than for percentage loss of active range of movement
      suggesting a pattern of end range pain may be less useful in identifying patients
      in this stage. CONCLUSIONS: External rotation movements in neutral and abduction
      generally group together and behave differently to other shoulder movements in
      patients clinically diagnosed with early stage primary/idiopathic adhesive
      capsulitis. In particular external rotation in abduction has emerged as the most
      painfully limited movement in this sample. This study provides preliminary
      evidence of patterns of range of movement and end range pain that require testing
      in a population of mixed shoulder diagnoses to determine their diagnostic utility
      for early stage adhesive capsulitis.

PMID- 24680793
TI  - The lipid raft-bound alkaline phosphatase activity increases and the level of
      transcripts remains unaffected in liver of merosin-deficient LAMA2dy mouse.
AB  - Alkaline phosphatase (AP) and other proteins add glycosylphosphatidylinositol
      (GPI) before addressing to raft domains of the cell membrane. Our previous report
      showing an increased density of lipid rafts in muscle of dystrophic Lama2dy mice
      prompted us to compare livers of normal (NL) and dystrophic mice (DL) for their
      levels of rafts. With this aim, hepatic rafts were isolated as Triton X-100
      resistant membranes, and identified by their abundance of flotillin-2, alkaline
      phosphatase (AP) and other raft markers. The comparable abundance of cholesterol
      and flotillin-2 in rafts of NL and DL contrasted with the double AP activity both
      in rafts of DL and whole DL. The AP mRNA level was the same in NL and DL.
      Sedimentation analysis profiles revealed AP activity of NL distributed between
      dimeric (dAP) and monomeric AP (mAP), whose proportions and lectin-binding extent
      changed in DL. The increased AP activity and changed AP glycosylation in DL, the
      prevalence of mAP in NL and the enhanced stability of dAP in DL demonstrated the
      critical role that glycosylation and oligomerization play for AP catalysis. The
      higher AP activity of DL probably arises from dystrophy-associated changes in
      glycosyl transferases, which alter AP glycosylation and subunit folding with
      profitable effects for AP stability and catalysis. 

PMID- 24680794
TI  - Trends in stroke rates, risk, and outcomes in the United States, 1988 to 2008.
AB  - BACKGROUND: Stroke is a major cause of morbidity and mortality. We describe
      trends in the incidence, outcomes, and risk factors for stroke in the US Medicare
      population from 1988 to 2008. METHODS: We analyzed data from a 20% sample of
      hospitalized Medicare beneficiaries with a principal discharge diagnosis of
      ischemic (n = 918,124) or hemorrhagic stroke (n = 133,218). Stroke risk factors
      were determined from the National Health and Nutrition Examination Survey (years
      1988-1994, 2001-2008) and medication uptake from the Medicare Current Beneficiary
      Survey (years 1992-2008). Primary outcomes were stroke incidence and 30-day
      mortality after stroke hospitalization. RESULTS: Ischemic stroke incidence
      decreased from 927 per 100,000 in 1988 to 545 per 100,000 in 2008, and
      hemorrhagic stroke decreased from 112 per 100,000 to 94 per 100,000. Risk
      adjusted 30-day mortality decreased from 15.9% in 1988 to 12.7% in 2008 for
      ischemic stroke and from 44.7% to 39.3% for hemorrhagic stroke. Although observed
      stroke rates decreased, the Framingham stroke model actually predicted increased
      stroke risk (mean stroke score 8.3% in 1988-1994, 8.8% in 2005-2008). Statin use
      in the general population increased (4.0% in 1992, 41.4% in 2008), as did
      antihypertensive use (53.0% in 1992, 73.5% in 2008). CONCLUSIONS: Incident
      strokes in the Medicare population aged >=65 years decreased by approximately 40%
      over the last 2 decades, a decline greater than expected on the basis of the
      population's stroke risk factors. Case fatality from stroke also declined.
      Although causality cannot be proven, declining stroke rates paralleled increased
      use of statins and antihypertensive medications.

PMID- 24680795
TI  - Premature mortality and comorbidities in young-onset diabetes: a 7-year
      prospective analysis.
AB  - BACKGROUND: There is an increasing prevalence of young-onset diabetes, especially
      in developing areas. We compared the clinical outcomes and predictors for
      cardiovascular-renal events between Chinese patients with type 2 diabetes with
      young- or late-onset of disease diagnosed before or after the age of 40 years,
      respectively. METHODS: The Hong Kong Diabetes Registry was established in 1995 as
      an ongoing quality improvement initiative with consecutive enrollment of diabetic
      patients from ambulatory settings for documentation of risk factors,
      microvascular and macrovascular complications, and clinical outcomes using a
      structured protocol. RESULTS: In 9509 Chinese patients with type 2 diabetes with
      a median (interquartile range) follow-up period of 7.5 (3.9-10.8) years, 21.3% (n
      = 2066) had young-onset diabetes. Despite 20 years difference in age, patients
      with young-onset diabetes (mean age, 41.3 years) had a similar or worse risk
      profile than those with late-onset disease (mean age, 61.9 years). Compared with
      the patients with late-onset diabetes, those with young-onset diabetes had lower
      rates of cardiovascular disease and chronic kidney disease for the same disease
      duration but a higher cumulative incidence of clinical events at any given age.
      With the use of stepwise Cox proportional hazard analysis, patients with young
      onset diabetes had higher risks for cardiovascular and renal events when adjusted
      by age, but no difference in risks than in the patients with late-onset diabetes
      when further adjusted by disease duration. CONCLUSIONS: Patients with young-onset
      diabetes had a similar or worse metabolic risk profile compared with those with
      late-onset disease. This group had higher risks for cardiovascular-renal
      complications at any given age, driven by longer disease duration.

PMID- 24680797
TI  - Matching energy intake to expenditure of isocaloric exercise at high- and
      moderate-intensities.
AB  - BACKGROUND: Those seeking to manage their bodyweight use a variety of strategies,
      but the most common approaches involve attempting to exercise more and/or consume
      fewer calories. A poor comprehension of the energy cost of exercise and the
      energy content of food may contribute to weight-gain and the poor success rate of
      exercise weight-loss interventions. PURPOSE: The purpose of this study is to
      investigate individuals' ability to consciously match energy intake with energy
      expenditure after isocaloric exercise at moderate and high intensities. METHOD:
      In a counterbalanced cross-over study design, 14 low- to moderately-active, lean
      individuals (7 male, 7 female; mean age 23+/-3 years; mean BMI 22.0+/-3.2 kg.m(
      2)) completed both a moderate-intensity (60% VO2max, MOD) and a high-intensity
      (90% VO2max, HIGH) exercise bout on a treadmill, matched for energy expenditure,
      EE (450 kcal). Participants were blinded to the intensity and duration of each
      bout. Thirty minutes post-exercise, participants were presented with a buffet,
      where they were asked to consume food in an attempt to match energy intake with
      the energy expended during the exercise bout. This was termed the "matching
      task," providing a matching task energy intake value (EI(MATCH)). Upon finishing
      the matching task, a verbal estimate of energy expenditure (EST) was obtained
      before the participant was allowed to return to the buffet to consume any more
      food, if desired. This intake was covertly measured and added to EI(MATCH) to
      obtain an ad libitum intake value (EI(AD LIB)). RESULTS: A significant condition
      * task interaction showed that, in MOD, EST was significantly lower than EE
      (298+/-156 kcal vs. 443+/-22 kcal, p=0.01). In the HIGH condition, EE, EI(MATCH)
      and EST were similar. In both conditions, participants tended to over-eat to a
      similar degree, relative to EST, with EI(MATCH) 20% and 22% greater than EST in
      MOD and HIGH respectively. Between-condition comparisons demonstrated that
      EI(MATCH) and EST were significantly lower in MOD, compared with HIGH (374+/-220
      kcal vs. 530+/-248 kcal, p=0.002 and 298+/-156 kcal vs. 431+/-129 kcal, p=0.002
      respectively). For both conditions, EI(AD LIB) was approximately 2-fold greater
      than EE. DISCUSSION: Participants exhibited a strong ability to estimate exercise
      energy expenditure after high-intensity exercise. Participants appeared to
      perceive moderate-intensity exercise to be less energetic than an isocaloric bout
      of high-intensity exercise. This may have implications for exercise
      recommendations for weight-loss strategies, especially when casual approaches to
      exercise and attempting to eat less are being implemented.

PMID- 24680798
TI  - Application of the equivalency factor concept to the phototoxicity and 
      genotoxicity of furocoumarin mixtures.
AB  - Furocoumarins (FCs) are natural constituents widely occurring in plants used as
      food or in phytomedicines, cosmetics, etc. Some FCs exert dermal photo-toxicity
      and -genotoxicity when combined with UVA irradiation. For a few congeners, skin
      tumor formation has been described in humans and laboratory animals. Since almost
      no information is available on the photo-toxic properties of several congeners,
      we analyzed the photo-cytotoxic, photo-mutagenic, and photo-clastogenic
      properties in V79 cells for thirteen naturally occurring FCs, and for the
      coumarin limettin. Furthermore, nine FC mixtures including one mixture based on
      the FC pattern of an Angelica archangelica extract were tested in the same
      assays. We found that the concept of relative potency factors for photo
      cytotoxic, -mutagenic, and -clastogenicpotencies of FCs, setting the value for 5
      methoxypsoralen at 1.00, was applicable to all congeners tested. The concept was
      used successfully to describe the photo-toxic properties of binary mixtures of 5-
      and 8-methoxypsoralen. Furthermore, the photo-genotoxic (photo-mutagenic and 
      clastogenic) properties of complex FC mixtures comprising up to nine different
      congeners could be predicted. These data suggest that FCs can differ widely in
      their photo-toxic and photo-genotoxic properties but show relatively strict
      additivity with respect to their on target-effects when occurring as complex
      mixtures. 

PMID- 24680796
TI  - Randomized controlled trial of sildenafil for preventing recurrent ischemic
      priapism in sickle cell disease.
AB  - BACKGROUND: Successful preventive therapy for ischemic priapism, a disorder of
      penile erection with major physical and psychologic consequences, is limited. We
      conducted a randomized, double-blind, placebo-controlled clinical trial to assess
      the efficacy and safety of sildenafil by a systematic dosing protocol to prevent
      recurrent ischemic priapism associated with sickle cell disease. METHODS:
      Thirteen patients with sickle cell disease reporting priapism recurrences at
      least twice weekly were randomized to receive sildenafil 50 mg or placebo daily,
      unassociated with sleep or sexual activity, for 8 weeks, followed by open-label
      use of this sildenafil regimen for an additional 8 weeks. RESULTS: Priapism
      frequency reduction by 50% did not differ between sildenafil and placebo groups
      by intention-to-treat or per protocol analyses (P = 1.0). However, during open
      label assessment, 5 of 8 patients (62.5%) by intention-to-treat analysis and 2 of
      3 patients (66.7%) by per protocol analysis met this primary efficacy outcome. No
      significant differences were found between study groups in rates of adverse
      effects, although major priapism episodes were decreased 4-fold in patients
      monitored "on-treatment." CONCLUSIONS: Sildenafil use by systematic dosing may
      offer a strategy to prevent recurrent ischemic priapism in patients with sickle
      cell disease.

PMID- 24680799
TI  - Study of the migration phenomena of specific metals in canned tomato paste before
      and after opening. Validation of a new quality indicator for opened cans.
AB  - A method for the simultaneous determination of Cd-Pb, As-Cu, Cr-Ni and Fe-Mn in
      canned tomato paste samples by Electrothermal Atomic Absorption Spectrometry was
      developed and validated. The validation procedure was conducted according to the
      terms of the European regulation for the official control of contaminants in
      foods. The validated method was applied for the determination of these metals and
      metalloids in 13 different tomato paste samples and the results showed that Cd
      content was higher than the maximum permissible value of 0.050 mg kg(-1) as
      proposed in European Regulation (EC) No 1881/2006 concerning fresh fruits and
      vegetables. Furthermore, a new quality indicator was evaluated in order to
      provide information about tomato paste quality and the appropriate storage time
      of an opened canned tomato paste. Finally, a migration test was accomplished
      based on the calculation of mass balance and the comparison of the elemental
      content in canned tomato paste samples and in aseptic paper pack and it was
      proved that Fe and Pb were the main metals migrating in tomato paste samples.

PMID- 24680800
TI  - Sex differences in attention Deficit Hyperactivity Disorder: candidate genetic
      and endocrine mechanisms.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a developmental condition
      characterised by severe inattention, pathological impulsivity and hyperactivity;
      it is relatively common affecting up to 6% of children, and is associated with a
      risk of long-term adverse educational and social consequences. Males are
      considerably more likely to be diagnosed with ADHD than females; the course of
      the disorder and its associated co-morbidities also appear to be sensitive to
      sex. Here, I discuss fundamental biological (genetic and endocrine) mechanisms
      that have been shown to, or could theoretically, contribute towards these
      sexually dimorphic phenomena. Greater understanding of how and why the sexes
      differ with respect to ADHD vulnerability should allow us to identify and
      characterise novel protective and risk factors for the disorder, and should
      ultimately facilitate improved diagnosis, prognosis and treatment. 

PMID- 24680801
TI  - Patients with hip fracture admitted to critical care: epidemiology, interventions
      and outcome.
AB  - INTRODUCTION: Although there is much current debate about the use of critical
      care to enhance peri-operative care of patients with hip fracture there are
      limited supporting data. We investigated the epidemiology, critical care
      interventions and outcomes of patients with hip fracture admitted to a large UK
      critical care unit. PATIENTS AND METHODS: We reviewed all patients with hip
      fracture (excluding those with multiple trauma, and those with femoral shaft or
      peri-prosthetic fracture) who were admitted to our critical care unit during a
      four year period. We recorded patient characteristics, reason for admission to
      critical care, interventions and organ support performed, and patient outcome.
      RESULTS: We identified 99 patients with a mean age of 81 years; this represented
      1% of patients admitted to critical care, and 2.4% of patients with hip fracture
      admitted to hospital during the study period. Fifty-two patients required no
      organ support; 19 received only respiratory support, 13 only cardiovascular
      support, 12 received both respiratory and cardiovascular support, and 3 received
      respiratory, cardiovascular and renal support. Outcome worsened as the level of
      organ support increased (p=0.01). Fifteen patients died in critical care, acute
      hospital mortality was 33% and 1-year mortality was 54%. No patient for whom
      admission was planned before surgery died in critical care and the 30-day
      mortality for this group was 13%. Outcome was related to the time between surgery
      and critical care admission: patients admitted before surgery or longer than 2
      days after surgery had worse outcomes (p=0.001). The reason for admission to
      critical care also influenced outcome: patients with sepsis had poor outcome with
      one-third dying in critical care and a further one-third not surviving to
      hospital discharge. CONCLUSIONS: The major determinants of outcome in this
      population were reason for admission, and timing of admission to critical care.
      One year survival was better than that for unselected patients aged >80 years
      admitted to critical care. Admission to critical care and use of enhanced peri
      operative care for selected hip fracture patients is entirely appropriate and
      beneficial.

PMID- 24680802
TI  - Some like it raw: an unwanted result of a sushi meal.

PMID- 24680803
TI  - Visual disturbances in total parenteral nutrition dependent liver transplant
      pediatric patient.

PMID- 24680804
TI  - Our new president--John I. Allen, MD, MBA, AGAF.

PMID- 24680805
TI  - Incidentally found unusual polyp on cecum.

PMID- 24680806
TI  - Large abdominal-pelvic tumors: a diagnostic conundrum.

PMID- 24680807
TI  - Sulfated modification of longan polysaccharide and its immunomodulatory and
      antitumor activity in vitro.
AB  - A water-soluble polysaccharide fraction (LP1) was prepared from Dimocarpus longan
      Lour. by hot water extraction, DEAE-cellulose and Sephadex G-100 chromatography.
      Its sulfated derivative (LP1-S) was prepared by the sulfuric acid method.
      Preliminary tests in vitro showed LP1 and LP1-S could stimulate murine
      lymphocytes proliferation, increase pinocytic activity of murine macrophages and
      production of nitric oxide (NO), interleukin 6 (IL-6), IL-1beta and tumor
      necrosis factor-alpha (TNF-alpha) in macrophages. Furthermore, LP1-S exhibited
      higher antiproliferative activity against human nasopharyngeal carcinoma HONE1
      cells in vitro than LP1, which might be caused by the sulfate group in its
      structures. These results indicated that the LP1-S might be useful for developing
      safe antitumor drugs or health food. 

PMID- 24680808
TI  - Structural diversity requires individual optimization of ethanol concentration in
      polysaccharide precipitation.
AB  - Ethanol precipitation is one of the most widely used methods for preparing
      natural polysaccharides, in which ethanol concentration significantly affects the
      precipitate yield, however, is usually set at 70-80%. Whether the standardization
      of ethanol concentration is appropriate has not been investigated. In the present
      study, the precipitation yields produced in varied ethanol concentrations (10
      90%) were qualitatively and quantitatively evaluated by HPGPC (high-performance
      gel-permeation chromatography), using two series of standard glucans, namely
      dextrans and pullulans, as reference samples, and then eight natural samples. The
      results indicated that the response of a polysaccharide's chemical structure,
      with diversity in structural features and molecular sizes, to ethanol
      concentration is the decisive factor in precipitation of these glucans.
      Polysaccharides with different structural features, even though they have similar
      molecular weights, exhibit significantly different precipitation behaviors. For a
      specific glucan, the lower its molecular size, the higher the ethanol
      concentration needed for complete precipitation. The precipitate yield varied
      from 10% to 100% in 80% ethanol as the molecular size increased from 1kDa to
      270kDa. This paper aims to draw scientists' attention to the fact that, in
      extracting natural polysaccharides by ethanol precipitation, the ethanol
      concentration must be individually optimized for each type of material. 

PMID- 24680809
TI  - Facile synthesis of cross linked-chitosan-grafted-polyaniline composite and its
      Cr(VI) uptake studies.
AB  - In the present investigation, the removal of Cr(VI) ions from aqueous solution
      using cross linked-chitosan-grafted-polyaniline composite (CCGP) was compared
      with that of chitosan-grafted-polyaniline (CGP) composite. The composites were
      characterized using FTIR, SEM-EDX, XRD, DSC, and TGA techniques. Batch
      equilibrium method was used for the optimization of various equilibrium
      parameters such as pH, contact time, dosage and initial Cr(VI) ion concentration.
      The removal efficiency by CCGP composite was found to be higher compared to CGP
      composite in all the studied conditions. The adsorption process was well
      described by Freundlich isotherm model for both the composites. The maximum
      adsorption capacity of CGP and CCGP composite for Cr(VI) ions was 165.6mg/g and
      179.2mg/g at 303K. Thermodynamic parameters for the adsorption system were
      calculated and concluded that the nature of sorption was spontaneous and
      endothermic in nature. The Cr(VI) adsorption kinetic process was well described
      by pseudo-second-order kinetic model and the sorption process was being
      controlled by intraparticle diffusion pattern. Desorption and regeneration
      experiments of CGP and CCGP composites were performed and reused for more than
      two consecutive cycles. 

PMID- 24680810
TI  - Bionic design for surface optimization combining hydrophilic and negative charged
      biological macromolecules.
AB  - While polyethersulfone (PES) membrane represents a promising option for blood
      purification, the blood compatibility must be dramatically enhanced to meet
      today's ever-increasing demands for many emerging application. In this study, we
      report a bionic design for optimization and development of a modified PES
      membrane combining hydrophilic and negative charged biological macromolecules on
      its surface. The hydrophilic and ionic charged biological macromolecules
      sulfonated poly(styrene)-b-poly(methyl methacrylate)-b-poly-(styrene) (PSSMSS)
      and poly(vinyl pyrrolidone)-b-poly(methyl methacrylate)-b-poly-(vinyl
      pyrrolidone) were synthesized via reversible addition-fragmentation chain
      transfer polymerization and used together to modify PES membranes by blending
      method. A hydrophilic membrane surface with negative charged surface coating was
      obtained, imitating the hydrophilic and negatively charged structure feature of
      heparin. The modified PES membranes showed suppressed platelet adhesion, and a
      prolonged blood clotting time, and thereby improved blood compatibility. In
      addition, the blood clotting time of the modified membranes increased with the
      blended PSSMSS amounts increment, indicating that both the hydrophilic and
      negative charged groups play important roles in improving the blood compatibility
      of PES membranes. 

PMID- 24680811
TI  - Properties and characteristics of dual-modified rice starch based biodegradable
      films.
AB  - In this study, the dual-modified rice starch was hydroxypropylated with 6-12% of
      propylene oxide followed by crosslinking with 2% sodium trimetaphosphate (STMP)
      and a mixture of 2% STMP and 5% sodium tripolyphosphate (STPP). Increasing the
      propylene oxide concentrations in the DMRS yielded an increase in the molar
      substitution (MS) and degree of substitution (DS). However, the gelatinization
      parameters, paste properties, gel strength and paste clarity showed an inverse
      trend. The biodegradable films from the DMRS showed an increase the tensile
      strength, elongation at break and film solubility, while the transparency value
      decreased when the concentration of propylene oxide increased. However the water
      vapor permeability of the films did not significantly change with an increase in
      the concentration of propylene oxide. In addition, it was found that DMRS films
      crosslinked with 2% STMP demonstrated higher tensile strength, transparency value
      and lower water vapor permeability than the DMRS films crosslinked with a mixture
      of 2% STMP and 5% STPP. The XRD analysis of the DMRS films showed a decrease in
      crystallinity when the propylene oxide concentrations increased and the
      crystallinity of DMRS films with 2% STMP were higher than the DMRS films with a
      mixture of 2% STMP and 5% STPP. 

PMID- 24680812
TI  - A study of neuroprotective and antioxidant activities of heteropolysaccharides
      from six Sargassum species.
AB  - Heteropolysaccharides were extracted from Sargassum integerrimum (S.I), Sargassum
      maclurei (S.M), Sargassum naozhouense (S.N), Spiraea thunbergii (S.T), Sargassum
      hemiphyllum (S.H) and Sargassum fusiforme (S.F), and their neuroprotective
      effects and antioxidant activities were investigated. It showed that S.I, S.N,
      S.T and S.F exhibited neuroprotective activities, whereas S.H and S.M did not.
      For this reason, they were separated by anion-exchange chromatography. It was
      apparent that the fraction 2 represented the principal difference between the
      active and non-active compounds. However, it did not correlate with
      neuroprotective effect. In addition, the results on antioxidant activities showed
      that the hydroxyl-radical scavenging effect contribute to the neuroprotective
      effect of S.T and S.N, and the DPPH-radical scavenging effect and reducing power
      contribute to S.T, S.F and S.I. However, the superoxide-radical scavenging effect
      did not correlate with neuroprotective activity. The conclusion was that the
      neuroprotective activity of the family of compounds investigated depended on a
      variety of factors. 

PMID- 24680813
TI  - Structural characterization of the polysaccharide moiety of an aqueous
      glycopeptide from mannatide.
AB  - A homogeneous glycopeptide with a molecular weight of 1.61*10(5)Da, termed as MT2
      A, was isolated from crude mannatide by DEAE-52 cellulose column and Sephacryl S
      300 gel column. The polysaccharide moiety of MT2-A was mainly composed of mannose
      and trace amount of glucose. Besides, MT2-A contained 16 kinds of amino acids and
      the total amino acid content was 4.41%. The detailed chemical structure of MT2-A
      was elucidated using methylation analysis, Fourier transform infrared
      spectroscopy (FT-IR), partial acid hydrolysis, selective acetolysis and 1D/2D
      nuclear magnetic resonance (NMR) spectroscopy. Based on the experimental results,
      it was concluded that the polysaccharide moiety of MT2-A had a backbone of (1->6)
      alpha-D-mannopyranose residues, which highly branched at O-2 position of (1->2,6)
      alpha-D-mannopyranose residues. The side chains were mainly composed of (1->)
      alpha-D-mannopyranose, (1->2)-alpha-D-mannopyranose and (1->3)-alpha-D
      mannopyranose residues. The length of the side chains could not be longer than
      four mannose residues. 

PMID- 24680814
TI  - Chitosan-ZnO/polyanilne nanocomposite modified glassy carbon electrode for
      selective detection of dopamine.
AB  - In this study, inorganic-organic redox mediators of CS-ZnO/PANI nanocomposite
      were synthesized by simple precipitation and chemical polymerization approach in
      the presence of chitosan (CS), ZnCl2, polyaniline (PANI) and ammonium
      peroxydisulfate (APS) as an initiator. The formation of ZnO nanoparticles onto CS
      PANI matrix was confirmed by SEM, TEM, Raman and FT-IR spectroscopies. Cyclic
      voltammetry and electrochemical impedance spectroscopy (EIS) were used to
      evaluate the electrochemical performance of the CS-ZnO/PANI. The obtained CS0.12
      ZC2.5/PANI nanocomposite modified electrode has been successfully developed for
      selective determination of dopamine (DA) in the presence of ascorbic acid (AsA)
      in 0.2M phosphate buffer solution pH 7.0. The electrochemical oxidation signals
      of AsA and DA are well separated into two distinct peak potential separation of
      303mV in DPV studies, which is large enough to allow the determination of one in
      the presence of the other. A linear response for DA concentrations range from
      20*10(-5) to 180*10(-5), in the presence of 140*10(-5) AsA, with sensitivity of
      0.013MUAMUM(-1) and a detection limit of 0.21MUM, have been obtained. Moreover,
      CS0.12-ZC2.5/PANI modified glassy carbon electrode (GCE) had good stability and
      antifouling properties. The proposed biosensor offers promise for simple and cost
      effective analysis of bio-molecules. 

PMID- 24680815
TI  - RASSF1A methylation may have two biological roles in neuroblastoma tumorigenesis
      depending on the ploidy status and age of patients.
AB  - RASSF1A methylation was frequent in neuroblastomas found in infants by mass
      screening or infants and children diagnosed clinically, whereas CASP8 and DCR2
      methylation was only frequent in tumors in children. When classified according to
      the ploidy status, RASSF1A and PCDHB methylation was only associated with MYCN
      amplification and poor outcomes in infants with a clinically diagnosed diploid,
      not triploid tumor. RASSF1A and PCDHB methylation was associated with poor
      outcomes in children with triploid and diploid tumors, respectively, and with
      MYCN amplification in children with diploid tumor. RASSF1A methylation may have
      two biological roles based on the ploidy status and patient's age. 

PMID- 24680816
TI  - Anti-tumor efficacy of a therapeutic peptide based on thermo-responsive elastin
      like polypeptide in combination with gemcitabine.
AB  - This work describes the effects of elastin-like polypeptide (ELP) with the
      p21(Waf1/Cip1)-derived cell cycle inhibitory peptide (p21) on pancreatic tumor
      cells with gemcitabine. The thermo-responsive property of ELP permits use of a
      mild, local hyperthermia to target tumors for the transport of chemotherapeutics.
      In this study, a p21-ELP construct with Bac cell penetrating peptide was
      designed, and its anticancer activities in pancreatic cancer cell lines was
      examined. In combination with gemcitabine, the peptide demonstrated enhanced in
      vitro cytotoxicity as well as tumor growth inhibition in an animal model. Our
      data suggest that this ELP construct, with gemcitabine, may improve pancreatic
      cancer therapy. 

PMID- 24680817
TI  - Cysteine cathepsins and extracellular matrix degradation.
AB  - BACKGROUND: Cysteine cathepsins are normally found in the lysosomes where they
      are involved in intracellular protein turnover. Their ability to degrade the
      components of the extracellular matrix in vitro was first reported more than
      25years ago. However, cathepsins were for a long time not considered to be among
      the major players in ECM degradation in vivo. During the last decade it has,
      however, become evident that abundant secretion of cysteine cathepsins into
      extracellular milieu is accompanying numerous physiological and disease
      conditions, enabling the cathepsins to degrade extracellular proteins. SCOPE OF
      VIEW: In this review we will focus on cysteine cathepsins and their extracellular
      functions linked with ECM degradation, including regulation of their activity,
      which is often enhanced by acidification of the extracellular microenvironment,
      such as found in the bone resorption lacunae or tumor microenvironment. We will
      further discuss the ECM substrates of cathepsins with a focus on collagen and
      elastin, including the importance of that for pathologies. Finally, we will
      overview the current status of cathepsin inhibitors in clinical development for
      treatment of ECM-linked diseases, in particular osteoporosis. MAJOR CONCLUSIONS:
      Cysteine cathepsins are among the major proteases involved in ECM remodeling, and
      their role is not limited to degradation only. Deregulation of their activity is
      linked with numerous ECM-linked diseases and they are now validated targets in a
      number of them. Cathepsins S and K are the most attractive targets, especially
      cathepsin K as a major therapeutic target for osteoporosis with drugs targeting
      it in advanced clinical trials. GENERAL SIGNIFICANCE: Due to their major role in
      ECM remodeling cysteine cathepsins have emerged as an important group of
      therapeutic targets for a number of ECM-related diseases, including,
      osteoporosis, cancer and cardiovascular diseases. This article is part of a
      Special Issue entitled Matrix-mediated cell behaviour and properties.

PMID- 24680818
TI  - Parvimonas micra as a causative organism of spondylodiscitis: a report of two
      cases and a literature review.
AB  - Spondylodiscitis caused by Parvimonas micra, a rarely reported infection, might
      be under-detected using conventional methods. This report of the detection and
      treatment of two cases of spondylodiscitis due to P. micra and review of the
      literature indicates that the use of gene sequencing methods might improve the
      accuracy of diagnosing this infection. 

PMID- 24680819
TI  - Respiratory symptoms in households as an effective marker for influenza-like
      illness surveillance in the community.
AB  - To effectively track the growth of influenza, we piloted an online system to
      monitor influenza-like illness (ILI) in the community in one district of Hong
      Kong. Four syndromic markers, namely fever, respiratory symptoms, fever with
      respiratory symptoms, fever and/or respiratory symptoms, either of the individual
      or of the household, were collected during the study period from June 2012 to
      October 2013. A total of 132 residents of Tuen Mun District reported syndromic
      markers at the individual and household levels on a weekly basis. Temporal
      patterns of these markers were compared with data derived from laboratory
      surveillance by dynamic linear regression. Household respiratory symptoms were
      found to be an effective syndromic marker, pre-dating overall laboratory virus
      surveillance results on influenza diseases in two influenza seasons by 3-4 weeks.
      To conclude, respiratory symptoms can be a good marker predicting the onset of
      the influenza season in the community, and is particularly useful with regard to
      data from households, even if the sample size may not be a large one. 

PMID- 24680820
TI  - Incidence and predictors of herpes zoster among antiretroviral therapy-naive
      patients initiating HIV treatment in Johannesburg, South Africa.
AB  - OBJECTIVES: To describe the characteristics of HIV-infected patients experiencing
      herpes zoster after antiretroviral therapy (ART) initiation and to describe the
      incidence and predictors of a herpes zoster diagnosis. METHODS: Adult patients
      initiating ART from April 2004 to September 2011 at the Themba Lethu Clinic in
      Johannesburg, South Africa were included. Patients were followed from ART
      initiation until the date of first herpes zoster diagnosis, or death, transfer,
      loss to follow-up, or dataset closure. Herpes zoster is described using incidence
      rates (IR) and predictors of herpes zoster are presented as subdistribution
      hazard ratios (sHR) and 95% confidence intervals (95% CI). RESULTS: Fifteen
      thousand and twenty-five patients were included; 62% were female, the median age
      was 36.6 years, and the median baseline CD4 count was 98 cells/mm(3). Three
      hundred and forty patients (2.3%) experienced herpes zoster in a median of 26.1
      weeks after ART initiation. Most (71.5%) occurred within 1 year of initiation,
      for a 1-year IR of 18.1/1000 person-years. In an adjusted model, patients with
      low CD4 counts (<50 vs. >=200 cells/mm(3); sHR: 1.71, 95% CI: 1.21-2.47) and with
      a prior episode of herpes zoster (sHR: 1.53, 95% CI: 0.97-2.28) were at increased
      risk of incident herpes zoster. CONCLUSIONS: While only 2% of patients were
      diagnosed with herpes zoster in this cohort, patients with low CD4 counts and
      those with prior episodes of herpes zoster were at higher risk for a herpes
      zoster diagnosis.

PMID- 24680821
TI  - Crystal structure of glycoside hydrolase family 127 beta-l-arabinofuranosidase
      from Bifidobacterium longum.
AB  - Enzymes acting on beta-linked arabinofuranosides have been unknown until
      recently, in spite of wide distribution of beta-l-arabinofuranosyl
      oligosaccharides in plant cells. Recently, a beta-l-arabinofuranosidase from the
      glycoside hydrolase family 127 (HypBA1) was discovered in the newly characterized
      degradation system of hydroxyproline-linked beta-l-arabinooligosaccharides in the
      bacterium Bifidobacterium longum. Here, we report the crystal structure of HypBA1
      in the ligand-free and beta-l-arabinofuranose complex forms. The structure of
      HypBA1 consists of a catalytic barrel domain and two additional beta-sandwich
      domains, with one beta-sandwich domain involved in the formation of a dimer.
      Interestingly, there is an unprecedented metal-binding motif with Zn(2+)
      coordinated by glutamate and three cysteines in the active site. The glutamate
      residue is located far from the anomeric carbon of the beta-l-arabinofuranose
      ligand, but one cysteine residue is appropriately located for nucleophilic attack
      for glycosidic bond cleavage. The residues around the active site are highly
      conserved among GH127 members. Based on biochemical experiments and quantum
      mechanical calculations, a possible reaction mechanism involving cysteine as the
      nucleophile is proposed.

PMID- 24680822
TI  - Crystal structures of Pseudomonas putida esterase reveal the functional role of
      residues 187 and 287 in substrate binding and chiral recognition.
AB  - A recombinant carboxylesterase (rPPE) from Pseudomonas putida ECU1011 was
      previously cloned and engineered to give a potential application for resolving
      chiral alpha-hydroxy acids including mandelic acids and derivatives. Two variants
      rPPEW187H and rPPED287A showed a ~100-fold increase in activity towards rac-2
      acetoxy-2-(2'-chlorophenyl) acetate (rac-AcO-CPA), but rPPED287A had a
      significant decrease in enantioselectivity (E=8.7) compared to rPPEW187H and the
      wild-type rPPE (rPPEWT) (E>200). Here we report the crystal structures of rPPEWT
      and rPPEW187H, both by themselves and in complex with the substrate, to elucidate
      the structural basis of this phenomenon. An inactive mutation of nucleophile
      residue S159A was introduced to obtain the structure of rPPES159A/W187H complexed
      with (S)-AcO-CPA. The structural analysis reveals that the side chain of residue
      Asp287 in rPPEWT would have a potential steric conflict with (S)-AcO-CPA when the
      substrate binds at the active site of the enzyme. However, the mutation W187H
      could facilitate the relocation of Asp287, while D287A directly eliminates the
      hindrance of Asp287, both of which offer sufficient space for the binding and
      hydrolysis of substrate. Moreover, Asp287 generates one site of the "three-point
      attachment model" as a hydrogen-bond donor that determines the excellent
      enantioselectivity of rPPE in chiral recognition, and D287A would obviously
      destroy the hydrogen bond and result in the low enantioselectivity of rPPED287A. 

PMID- 24680823
TI  - Influence of olive-derived hydroxytyrosol on the toll-like receptor 4-dependent
      inflammatory response of mouse peritoneal macrophages.
AB  - Macrophages play important roles in the host innate immune response and are
      involved in the onset of diseases caused by inflammation. Toll-like receptor 4
      (TLR4)-mediated inflammatory responses of macrophages may be associated with
      diseases such as diabetes and diseases of the cardiovascular system.
      Hydroxytyrosol (HT) exerts strong antioxidant and anti-inflammatory effects and
      may be applied in the treatment of inflammatory diseases. In the present study
      conducted in vitro, we investigated the effects of the TLR4-dependent anti
      inflammatory effect of HT on peritoneal macrophage of BALB/c mice. We show here
      that the elevated levels of iNOS gene expression and nitric oxide production
      induced by lipopolysaccharide (LPS) (0.25 MUg/ml) were suppressed by HT (12.5
      MUg/ml). LPS-dependent NF-kappaB gene expression and phosphorylation of NF-kappaB
      were not affected by HT under these conditions. In contrast, the expression of
      TNF-alpha was significantly increased in the presence of LPS and HT. These
      results suggest that HT suppressed nitric oxide production by decreasing iNOS
      gene expression through a mechanism independent of the NF-kappaB signaling
      pathway. These novel findings suggest that the modulation by HT of the expression
      of genes involved in inflammation may involve multiple mechanisms.

PMID- 24680824
TI  - Pontin is required for pre-TCR signaling at the beta-selection checkpoint in T
      cell development.
AB  - Pontin is a chromatin remodeling factor that possesses both ATPase and DNA
      helicase activities. Based on high expression in lymphoid tissues, we examined
      whether Pontin has a T cell-specific function. We generated Pontin(f/f);Lck-Cre
      mice, in which Pontin can be conditionally deleted in T cells and then explored T
      cell-specific function of Pontin in vivo. Here, we show that specific abrogation
      of Pontin expression in T cells almost completely blocked development of
      alphabeta T cells at the beta-selection checkpoint by inducing cell apoptosis
      indicating that Pontin is essential for early T cell development. Pontin
      deficient thymocytes show a comparable expression level of T cell receptor
      (TCR)beta chain, but have enhanced activation of p53 and Notch signaling compared
      to wild-type thymocytes. Intriguingly, the developmental block of alphabeta T
      cells can be partially rescued by loss of p53. Together, our data demonstrate a
      novel role of Pontin as a crucial regulator in pre-TCR signaling during T cell
      development.

PMID- 24680825
TI  - Cell-to-cell propagation of intracellular signals fluorescently visualized with
      acridine orange in the gastric glands of guinea pigs.
AB  - Secretion from the gastric gland involves the activation of various types of
      cells in a coordinated manner. In order to elucidate the mechanisms underlying
      the coordination of secretion, we studied live fluorescence images of guinea pig
      gastric glands stained with acridine orange (AO). On 2 MUM AO staining,
      individual cells were characterized by metachromatic colors and various
      intensities of fluorescence. When the gland was stimulated with 100 MUM of
      histamine, green fluorescence was transiently increased in parietal cells and
      intermediate cells and propagated along the gland for a long distance over many
      cells. Local stimulation in a couple of cells with histamine in the presence of
      suramin also induced propagation. However, the fluorescence response was
      suppressed by the addition of H-89, a protein kinase A inhibitor. These findings
      suggest that a cAMP-dependent signal propagates intercellularly through a variety
      of cells to induce coordinated secretion in the entire gastric gland.

PMID- 24680826
TI  - KLF15 regulates slow myosin heavy chain expression through NFATc1 in C2C12
      myotubes.
AB  - A comprehensive understanding of genetic and environmental factors that control
      skeletal muscle fiber type specification and transformation is essential not only
      in sports science, but also in myopathy and metabolic disorders. Kruppel-like
      factors (KLFs) are a subfamily of the zinc-finger class of transcription factors,
      which are involved in the development, homeostasis, and pathology of
      cardiovascular systems. Compared to cardiac and smooth muscles, the role of KLFs
      in skeletal muscle is much less understood. In this study, the endogenous
      expression of KLF15 was analyzed in differentiating C2C12 muscle cells and mouse
      skeletal muscle. Our data indicated that Klf15 was upregulated during myogenic
      differentiation and higher levels of Klf15 mRNA were detected in mouse slow,
      oxidative soleus muscle (SL) compared to that in fast, glycolytic tibialis
      anterior muscle (TA), indicating that KLF15 may play a role in myogenesis or
      myofiber typing. Additional studies revealed that KLF15 regulated the expression
      of MHC-beta/slow rather than muscle cell differentiation. Gene silencing,
      overexpression, and luciferase reporter assay showed that KLF15 regulated MHC
      beta/slow by binding to Nfatc1 promoter, inducing its activity, therefore
      mediating calcineurin/NFAT signaling. Our study contributed to the current
      knowledge on KLFs in skeletal muscle, and it indicated a need for further
      intensive studies on the redundant and divergent functions of KLFs. 

PMID- 24680827
TI  - Epigenetic regulation in amyloid precursor protein and the Lesch-Nyhan syndrome.
AB  - Lesch-Nyhan syndrome (LNS) is a neurogenetic disorder of purine metabolism in
      which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HPRT) is
      defective. A major unsolved question is how the loss of HPRT enzyme function
      affects the brain to cause the neurobehavioural syndrome in LNS and its
      attenuated variants (LNVs). To address this issue, a search for a link between
      LNS and the amyloid precursor protein (APP) is developed. Here, I identified, for
      the first time in fibroblasts from normal subjects as well as from LNS and LNV
      patients: (a) several APP-mRNA isoforms encoding divers APP protein isoforms
      ranging from 120 to 770 amino acids (with or without mutations and/or deletions)
      accounted for epigenetic mechanisms in the regulation of alternative APP pre-mRNA
      splicing and (b) five novel independent polymorphisms in the APP promoter: 
      956A>G, -1023T>C, -1161A>G, -2224G>A, -2335C>T relative to the transcription
      start site. A role for epistasis between mutated HPRT and APP genes affecting the
      regulation of alternative APP pre-mRNA splicing in LNS is suggested. An accurate
      quantification of various APP isoforms in brain tissues for detection of initial
      pathological changes or pathology development is needed. My findings may provide
      new directions not only for investigating the role of APP in neuropathology
      associated with HPRT-deficiency in LNS but also for the research in
      neurodevelopmental and neurodegenerative disorders by which various APP isoforms
      involved in the pathogenesis of the diseases such as Alzheimer's disease. 

PMID- 24680829
TI  - Mechanical and metabolic reflex activation of the sympathetic nervous system in
      younger adults with metabolic syndrome.
AB  - AIM: Based on reports of exaggerated blood pressure responses to whole-body
      exercise in patients with metabolic syndrome (MetSyn), we tested the hypothesis
      that MetSyn adults would exhibit augmented sympathetic and pressor responses to
      mechanoreflex and metaboreflex activation when compared with healthy, age-matched
      control subjects. METHODS: We studied 12 adults with MetSyn (34+/-3years) and 12
      healthy control subjects (34+/-3years). Heart rate (HR; ECG), blood pressure (BP;
      finger photoplethysmography), and MSNA (microneurography of the peroneal nerve)
      were measured during: (1) static handgrip exercise at 15% of maximal voluntary
      contraction (MVC), and (2) static handgrip exercise at 30% MVC to fatigue,
      followed by post-exercise ischemia (PEI). Increases in MSNA, HR, and BP were
      assessed. RESULTS: During static exercise at both 15 and 30% MVC, increases in
      MSNA, HR, and BP were not different between groups. MSNA remained significantly
      elevated from baseline during PEI and responses were not different between
      groups. CONCLUSION: Sympathetic and pressor responses to mechanoreflex and
      metaboreflex activation are not augmented in younger adults with MetSyn.

PMID- 24680828
TI  - Cellular accumulation of Cys326-OGG1 protein complexes under conditions of
      oxidative stress.
AB  - The common Ser326Cys polymorphism in the base excision repair protein 8
      oxoguanine glycosylase 1 is associated with a reduced capacity to repair
      oxidative DNA damage particularly under conditions of intracellular oxidative
      stress and there is evidence that Cys326-OGG1 homozygous individuals have
      increased susceptibility to specific cancer types. Indirect biochemical studies
      have shown that reduced repair capacity is related to OGG1 redox modification and
      also possibly OGG1 dimer formation. In the current study we have used bimolecular
      fluorescence complementation to study for the first time a component of the base
      excision repair pathway and applied it to visualise accumulation of Cys326-OGG1
      protein complexes in the native cellular environment. Fluorescence was observed
      both within and around the cell nucleus, was shown to be specific to cells
      expressing Cys326-OGG1 and only occurred in cells under conditions of cellular
      oxidative stress following depletion of intracellular glutathione levels by
      treatment with buthionine sulphoximine. Furthermore, OGG1 complex formation was
      inhibited by incubation of cells with the thiol reducing agents beta
      mercaptoethanol and dithiothreitol and the antioxidant dimethylsulfoxide
      indicating a causative role for oxidative stress in the formation of OGG1
      cellular complexes. In conclusion, this study has provided for the first time
      evidence of redox sensitive Cys326-OGG1 protein accumulation in cells under
      conditions of intracellular oxidative stress that may be related to the
      previously reported reduced repair capacity of Cys326-OGG1 specifically under
      conditions of oxidative stress.

PMID- 24680830
TI  - In vitro immune functions in thiamine-replete and -depleted lake trout
      (Salvelinus namaycush).
AB  - In this study we examined the impacts of in vivo thiamine deficiency on lake
      trout leukocyte function measured in vitro. When compared outside the context of
      individual-specific thiamine concentrations no significant differences were
      observed in leukocyte bactericidal activity or in concanavalin A (Con A), and
      phytohemagglutinin-P (PHA-P) stimulated leukocyte proliferation. Placing immune
      functions into context with the ratio of in vivo liver thiamine monophosphate
      (TMP--biologically inactive form) to thiamine pyrophosphate (TPP--biologically
      active form) proved to be the best indicator of thiamine depletion impacts as
      determined using regression modeling. These observed relationships indicated
      differential effects on the immune measures with bactericidal activity exhibiting
      an inverse relationship with TMP to TPP ratios, Con A stimulated mitogenesis
      exhibiting a positive relationship with TMP to TPP ratios and PHA-P stimulated
      mitogenesis exhibiting no significant relationships. In addition, these
      relationships showed considerable complexity which included the consistent
      observation of a thiamine-replete subgroup with characteristics similar to those
      seen in the leukocytes from thiamine-depleted fish. When considered together, our
      observations indicate that lake trout leukocytes experience cell-type specific
      impacts as well as an altered physiologic environment when confronted with a
      thiamine-limited state.

PMID- 24680831
TI  - Differential regulation of Tetraodon nigroviridis Mx gene promoter activity by
      constitutively-active forms of STAT1, STAT2, and IRF9.
AB  - Induction of interferons (IFNs) produces an innate immune response through
      activation of the JAK-STAT signaling pathway. Type I IFN signaling activates
      downstream gene expression through the IFN-stimulated gene factor 3 (ISGF3)
      complex, while type II IFN (IFN-gamma) signaling is mediated through active STAT1
      protein. The IFN target gene Mx is involved in the defense against viral
      infection. However, the mechanism by which Tetraodon (pufferfish) Mx is regulated
      by IFN signaling has not been identified. In this study, we describe the cloning
      and expression of Tetraodon STAT1, STAT2, and IFN regulatory factor 9 (IRF9). By
      combining constitutively-active STAT1 (STAT1-JH1) and STAT2 (STA2-JH1) fusion
      proteins with IRF9, we demonstrate that a constitutively-active ISGF3 complex
      increases the transcriptional activity of the Tetraodon Mx promoter via direct
      binding to two IFN-stimulated response element (ISRE) sites. In addition, a
      constitutively-active TnIRF9-S2C containing a fusion of the C-terminal region of
      STAT2 and IRF9 also activated the Mx promoter through binding to the ISRE sites.
      Furthermore, constitutively-active STAT1-JH1 elevates Mx promoter activity
      through two IFN gamma-activated sequence (GAS) elements. The Mx promoter is also
      activated by constitutively-active TnIRF9-S2C and STAT1-JH1 protein, as
      determined using an in vivo luciferase assay. We conclude that the Tetraodon Mx
      gene is activated via Type I (IFN-1) and Type II (IFN-gamma) signaling. These
      results provide mechanistic insights into the role of IFN signaling in teleosts,
      and the in vivo luciferase assay may be suitable as a tool for studying induction
      and regulation by IFNs in teleost fish.

PMID- 24680832
TI  - [Epidemiology, treatment and follow-up of central nervous system
      hemangioblastomas in von Hippel-Lindau disease].
AB  - INTRODUCTION: Central nervous system (CNS) hemangioblastomas (HGB) are rare
      vascular tumors. The goal of this study was to analyze their epidemiology,
      treatment and prognosis in association with von Hippel-Lindau (VHL) disease.
      METHODS: We retrospectively reviewed a series of patients treated in our
      department for a CNS HGB with VHL disease between 1996 and 2008. We analyzed pre-
      and postoperative clinical and radiological characteristics, number of visceral
      lesions (fundoscopy, abdomino-pelvian CT, metanephrines), clinical course
      (modified Rankin Scale and McCormick scale) and late prognosis (Kaplan-Meier
      survival curves). RESULTS: We studied 19 cases (sex-ratio 0.9, mean age 36). The
      mean time to diagnosis was 61days. The main symptom was intracranial hypertension
      for cerebellar lesions (7/15) and a sensitive-motor deficit for medulla oblongata
      (2/5) or spinal lesions (5/11). Preferred locations were cerebellum (15/31),
      often nodulo-cystic appearance, followed by spinal cord (11/31), frequently
      coming with adjacent syringomyelia. Multiple locations and visceral lesions were
      found in two-third of the cases. Surgical removal was complete in more than three
      quarter of the cases. Mean follow-up duration was 9years. Postoperative mortality
      rate was 16%. In cerebellar and medulla oblongata locations together, final mRS
      was <=1 in 17 of the 20 cases. In spinal cord locations, final McCormick score
      was <=2 in all the cases. After delayed follow-up, about two-third of patients
      experienced recurrence or new progressive CNS lesions. CONCLUSION: HGB are rare
      CNS tumors. VHL disease should be considered when an HGB is diagnosed before 30,
      is located at the spinal cord, comes with multiple other CNS lesions or with
      typical peripheral lesions. Microsurgical removal is the gold standard treatment
      and can offer good functional results.

PMID- 24680833
TI  - Activity-based proteomics probes for carbohydrate-processing enzymes: current
      trends and future outlook.
AB  - Carbohydrate-processing enzymes are gaining more attention due to their roles in
      health and disease as these enzymes are involved in the construction and
      deconstruction of vast arrays of glycan structures. As a result, the development
      of methods to identify these enzymes in complex biological systems is of
      increasing interest. Activity-based proteomics probes (ABPPs) are increasingly
      being used in glycobiology to detect and identify functionally related proteins
      (and homologues) within a biological system. This review will describe the design
      of activity-based proteomics probes, provide examples of compounds that have been
      used to profile activity in the area of carbohydrate-processing enzymes, and give
      some future perspectives. 

PMID- 24680835
TI  - Evolutionary analysis revealed the horizontal transfer of the Cyt b gene from
      Fungi to Chromista.
AB  - In this study, the cytochrome b (Cyt b) amino acid sequences were analyzed in 50
      organisms covering all 5 kingdoms of eukaryotes. Six conserved domains, i.e.,
      heme bL binding sites, heme bH binding sites, Qo binding sites, Qi binding sites,
      the interchain domain interface, and the intrachain domain interface were found
      in all investigated sequences. The topology of the phylogenetic trees was largely
      consistent with the well recognized taxonomic relationships, indicating that the
      Cyt b genes originated from a common ancestral gene before the divergence of
      eukaryotic kingdoms. The eukaryotic Cyt b genes likely originated from an ancient
      prokaryotic gene in Alphaproteobacteria based on shared conserved domains. We
      provide evidence that the Cyt b gene of oomycete Pseudoperonospora cubensis was
      horizontally transferred from a fungus in the order Hypocreales. To our
      knowledge, this is the first reported evidence of Horizontal gene transfer (HGT)
      from Fungi to Chromista involving an essential house-keeping gene. Our data
      suggest that HGT events must be considered when evolutionary trees are
      constructed only based on Cyt b genes. Additional analysis of thousands of Cyt b
      sequences from Genbank revealed that introns in mitochondrial Cyt b genes were
      acquired after the endosymbiosis of alphaproteobacteria in eukaryotic cells. 

PMID- 24680836
TI  - Lanthanide and transition metal complexes of bioactive coumarins: molecular
      modeling and spectroscopic studies.
AB  - The present paper summarizes theoretical and spectroscopic investigations on a
      series of active coumarins and their lanthanide and transition metal complexes
      with application in medicine and pharmacy. Molecular modeling as well as IR,
      Raman, NMR and electronic spectral simulations at different levels of theory were
      performed to obtain important molecular descriptors: total energy, formation
      energy, binding energy, stability, conformations, structural parameters, electron
      density distribution, molecular electrostatic potential, Fukui functions, atomic
      charges, and reactive indexes. The computations are performed both in gas phase
      and in solution with consideration of the solvent effect on the molecular
      structural and energetic parameters. The investigations have shown that the
      advanced computational methods are reliable for prediction of the metal-coumarin
      binding mode, electron density distribution, thermodynamic properties as well as
      the strength and nature of the metal-coumarin interaction (not experimentally
      accessible) and correctly interpret the experimental spectroscopic data. Known
      results from biological tests for cytotoxic, antimicrobial, anti-fungal,
      spasmolytic and anti-HIV activities on the studied metal complexes are reported
      and discussed. 

PMID- 24680834
TI  - CDKN2B expression and subcutaneous adipose tissue expandability: possible
      influence of the 9p21 atherosclerosis locus.
AB  - Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent
      genetic determinant of cardiovascular disease. Previous research has demonstrated
      that 9p21 risk variants influence gene expression in vascular tissues, yet the
      biological mechanisms by which this would mediate atherosclerosis merits further
      investigation. To investigate possible influences of this locus on other tissues,
      we explored expression patterns of 9p21-regulated genes in a panel of multiple
      human tissues and found that the tumor suppressor CDKN2B was highly expressed in
      subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity
      status, and this effect was stronger in carriers of 9p21 risk alleles.
      Covariation between expression of CDKN2B and genes implemented in adipogenesis
      was consistent with an inhibitory effect of CDKN2B on SAT proliferation.
      Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B
      is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression
      in SAT correlated with indicators of ectopic fat accumulation, including markers
      of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears
      to play a significant role in the regulation of SAT expandability, which is a
      strong determinant of lipotoxicity and therefore might contribute to the
      development of atherosclerosis. 

PMID- 24680837
TI  - The error processing system in major depressive disorder: cortical phenotypal
      marker hypothesis.
AB  - Major depressive disorder (MDD) ensues reduced goal-directed cognition and
      behaviour. Cognitive and emotional flexibility to disengage and adapt future
      responses was examined in the error processing system (error-related
      negativity/ERN, error-positivity/Pe event-related potentials) of 58 depressed
      patients (21 current, 37 remitted) vs. 27 controls undergoing cognitive and
      affective Go/NoGo paradigms. ERN was equivalent between patient and controls for
      the cognitive task, albeit amplitude attenuated in patients during the affective
      task. Blunted ERN amplitudes were evident between patients and controls in males
      compared to females, plausibly underpinned by disparities in dopaminergic
      pathways. Patients displayed enhanced Pe amplitudes for both cognitive and
      affective tasks. Abberations in cortical error processing in MDD appear specific
      to affective systems for the pre-attentive ERN, opposed to cognitive and
      affective processing for the consciously-integrated Pe. Heightened Pe, observed
      in both current and remitted patients, advocates the possibility of the Pe
      waveform as a candidate intermediate phenotype of depression. 

PMID- 24680839
TI  - Myostatin - From the Mighty Mouse to cardiovascular disease and cachexia.
AB  - In 1997, McPherron et al. created the so-called Mighty Mouse: owing to the knock
      out of a new member of the TGF-beta superfamily of peptides, this mouse line was
      extremely hypermuscular and also characterized by very low body fat. The new
      peptide, a powerful negative muscle regulator, was named myostatin. Apart from
      regulating skeletal muscle growth, myostatin has recently been reported to be
      significantly involved in different cardio-vascular and metabolic pathologies.
      This review is focused on these non-muscular myostatin actions. First, myostatin
      is intricately involved in regulating metabolism: it causes insulin resistance,
      and the advantageous metabolic profile achieved by myostatin inhibition is mainly
      attributable to its effects on skeletal muscle. Myostatin is further expressed in
      myocardium where it exerts anti-hypertrophic, but pro-fibrotic effects.
      Circulating and local myostatin is elevated in chronic heart failure and poses a
      major player in cardiac cachexia. Eventually, the current body of evidence
      regarding myostatin's significant involvement in different entities of the
      cachexia syndrome is summarized. Activin type-2 receptor antagonism and/or
      inhibitory myostatin antibodies have emerged as a promising therapeutic approach
      to treat the cachexia syndrome although the general applicability of this
      therapeutic approach to the human clinical situation has still to be
      demonstrated. 

PMID- 24680838
TI  - Vulnerability of welders to manganese exposure--a neuroimaging study.
AB  - Increased manganese (Mn) exposure is known to cause cognitive, psychiatric and
      motor deficits. Mn exposure occurs in different occupational settings, where the
      airborne Mn level and the size of respirable particulates may vary considerably.
      Recently the importance of the role of the cerebral cortex in Mn toxicity has
      been highlighted, especially in Mn-induced neuropsychological effects. In this
      study we used magnetic resonance imaging (MRI) to evaluate brain Mn accumulation
      using T1 signal intensity indices and to examine changes in brain iron content
      using T2* contrast, as well as magnetic resonance spectroscopy (MRS) to measure
      exposure-induced metabolite changes non-invasively in cortical and deep brain
      regions in Mn-exposed welders, Mn-exposed smelter workers and control factory
      workers with no measurable exposure to Mn. MRS data as well as T1 signal
      intensity indices and T2* values were acquired from the frontal cortex, posterior
      cingulate cortex, hippocampus, and thalamus. Smelters were exposed to higher air
      Mn levels and had a longer duration of exposure, which was reflected in higher Mn
      levels in erythrocytes and urine than in welders. Nonetheless, welders had more
      significant metabolic differences compared to controls than did the smelter
      workers, especially in the frontal cortex. T1 hyperintensities in the globus
      pallidus were observed in both Mn-exposed groups, but only welders showed
      significantly higher thalamic and hippocampal T1 hyperintensities, as well as
      significantly reduced T2* values in the frontal cortex. Our results indicate that
      (1) the cerebral cortex, in particular the frontal cortex, is clearly involved in
      Mn neurotoxic effects and (2) in spite of the lower air Mn levels and shorter
      duration of exposure, welders exhibit more extensive neuroimaging changes
      compared to controls than smelters, including measurable deposition of Mn in more
      brain areas. These results indicate that the type of exposure (particulate sizes,
      dust versus fume) and route of exposure play an important role in the extent of
      Mn-induced toxic effects on the brain. 

PMID- 24680840
TI  - Profile of women seeking medical termination of pregnancy in South India.
AB  - OBJECTIVE: To investigate the demographic and obstetric profile of women seeking
      medical termination of pregnancy (MTP) in South India in accordance with the MTP
      Act of India. METHODS: A registry-based retrospective study was carried out at a
      tertiary care teaching hospital in South India. The hospital records of all
      pregnant women seeking MTP over a 2-year period between January 2011 and December
      2012 were reviewed. RESULTS: A total of 244 women underwent MTP during the study
      period. More than one-third (37.8%) were aged between 26 and 30 years. The
      majority of women underwent MTP during the first trimester (79.5%). Medical
      reasons were cited as the most common reason for undergoing MTP (39.3%), followed
      by unplanned pregnancy (34.8%). The majority of women were seeking MTP for the
      first time (84.8%). More than half of the women (52.9%) opted for post-MTP
      contraception. CONCLUSION: MTP for unplanned pregnancy can be prevented if people
      are well informed about methods of contraception. MTP is an opportunity for
      healthcare professionals to discuss fertility needs and need for contraception
      with women seeking MTP so that appropriate decisions can be taken for suitable
      family planning.

PMID- 24680842
TI  - Fetal brain magnetic resonance imaging and long-term neurodevelopmental
      impairment.
AB  - OBJECTIVE: To determine the incidence of fetal brain injury by fetal brain
      magnetic resonance imaging (MRI) in pregnancies complicated with preterm labor
      (PL), preterm premature rupture of the membranes (PPROM), and intrauterine growth
      restriction (IUGR), and to compare fetal brain MRI with prenatal surveillance
      methods, and with immediate and long-term neurodevelopmental outcome. METHODS:
      Between February 2007 and January 2009, high-risk pregnancies were analyzed by
      MRI at 1.5 Tesla after 24 weeks of gestation at the Clinical Hospital Center
      Zagreb, Croatia. Long-term outcome was defined as neurodevelopmental outcome at
      24 months. RESULTS: Among 70 pregnancies analyzed, 40.0% had abnormal fetal brain
      MRI. The highest incidence occurred in the PL group. There was no correlation
      between abnormal MRI and fetal surveillance methods (ultrasound, Doppler blood
      flow analysis, cardiotocography, biophysical profile) or immediate neonatal
      outcome (1-minute Apgar score, umbilical cord pH). Via MRI, fetal brain injury
      would have been diagnosed for 45.7% of fetuses with a long-term
      neurodevelopmental handicap. Binary logistic regression showed that, as compared
      with other surveillance methods, fetal brain MRI was the best predictor of long
      term neurodevelopmental disability. CONCLUSION: PL, IUGR, and PPROM were
      associated with an early intrauterine CNS insult that was not accurately detected
      by existing prenatal testing options.

PMID- 24680841
TI  - Assessment of "fresh" versus "macerated" as accurate markers of time since
      intrauterine fetal demise in low-income countries.
AB  - OBJECTIVE: To compare provider assessment of fetal maceration with death-to
      delivery interval to evaluate the reliability of appearance as a proxy for time
      of death. METHODS: Cohort chart abstraction was performed for all stillbirth
      deliveries at or above 28 weeks of gestation during a 1-year period in a teaching
      hospital in Ghana. RESULTS: Of 470 stillborn infants, 337 had adequate data for
      analysis. Of 47 fetuses alive on admission with death-to-delivery intervals
      estimated to be less than 8 hours (expected to be reported as fresh), 14 (30%)
      were actually reported as macerated. Of 94 cases in which the fetus was deceased
      on admission with death-to-delivery interval of more than 8 hours (expected to be
      macerated), 17 (18%) were described as fresh. CONCLUSION: Provider description of
      fetal appearance may be an unreliable indicator for time since fetal death. The
      findings have significant implications for stillbirth prevention and assessment.

PMID- 24680843
TI  - Hydrosonographic assessment of the effects of 2 different suturing techniques on
      healing of the uterine scar after cesarean delivery.
AB  - OBJECTIVE: To compare the effects of 2 suturing techniques (single versus double
      layer) on healing of the uterine scar after a cesarean delivery. METHODS: In the
      present randomized, prospective study, 36 women with a term pregnancy who had an
      elective cesarean delivery were randomly assigned to closure of the uterine
      incision with a single-layer locked suture or with a double-layer locked/unlocked
      suture. Six months after the operation, the integrity of the cesarean scar at the
      uterine incision site was assessed by hydrosonography. The healing ratio and the
      thickness of the residual myometrium covering the defect were calculated as
      markers of uterine scar healing. RESULTS: There were no significant differences
      between the groups in terms of estimated blood loss, operation time, or
      additional hemostatic suture. However, the mean thickness of the residual
      myometrium covering the defect was 9.95 +/- 1.94 mm after a double-layer closure
      and 7.53 +/- 2.54 mm after a single-layer closure (P = 0.005). The mean healing
      ratio was significantly higher after a double-layer closure (0.83 +/- 0.10) than
      after a single-layer closure (0.67 +/- 0.15; P = 0.004). CONCLUSION: A double
      layer locked/unlocked closure of the uterine incision at cesarean delivery
      decreases the risk of poor uterine scar healing.

PMID- 24680844
TI  - Guest editorial: pharmacology of male sexual behavior.

PMID- 24680845
TI  - Current opinion in superspreading mechanisms.
AB  - BACKGROUND: An aqueous solution of trisiloxane-ethoxylate surfactants
      (superspreaders) has fascinating surface properties that promote rapid spreading
      over a large area of difficult-to-wet substrates. The overall spread area
      achieved by an aqueous droplet containing superspreaders can be as much as 50
      times greater than water, and 25 times more effective than a conventional
      surfactant on a leaf's surface. The phenomenon that drives superspreading is
      still not well understood and it is under continuous discussion. CONCEPTS AND
      MODELS: The goal of this paper is to review the data published to elucidate the
      concepts and mechanisms presented in the literature and to propose a model for
      superspreading. CONCLUSIONS: A simple model was proposed concerning the surface
      tension gradient (or Marangoni flow) over the curved droplet surface when the
      value of the wetting angle was considered. The model predicted the optimum rate
      of spreading vs. angle at theta = 60 degrees  and was in a satisfactory agreement
      with the experimental observations.

PMID- 24680846
TI  - Perfluorinated chemicals: differential toxicity, inhibition of aromatase activity
      and alteration of cellular lipids in human placental cells.
AB  - The cytotoxicity of eight perfluorinated chemicals (PFCs), namely,
      perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic
      acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA),
      perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and
      perfluorooctanesulfonate (PFOS) was assessed in the human placental
      choriocarcinoma cell line JEG-3. Only the long chain PFCs--PFOS, PFDoA, PFNA,
      PFOA--showed significant cytotoxicity in JEG-3 cells with EC50 values in the
      range of 107 to 647 MUM. The observed cytotoxicity was to some extent related to
      a higher uptake of the longer chain PFCs by cells (PFDoA>PFOS?PFNA>PFOA>PFHxA).
      Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as
      aromatase inhibitors in placental cells with IC50s in the range of 57-80 MUM, the
      inhibitory effect of PFBS being particularly important despite the rather low
      uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of
      the eight PFCs (0.6 MUM each) led to a relative increase (up to 3.4-fold) of
      several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and
      lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids.
      Overall, this work highlights the ability of the PFC mixture to alter cellular
      lipid pattern at concentrations well below those that generate toxicity, and the
      potential of the short chain PFBS, often considered a safe substitute of PFOS, to
      significantly inhibit aromatase activity in placental cells.

PMID- 24680847
TI  - Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in
      vivo.
AB  - The purpose of this study was to investigate the enhancing effect of dioscin on
      the absorption of methotrexate (MTX) and clarify the molecular mechanism involved
      in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial
      flux in the absorptive direction, significantly inhibiting multidrug resistance 1
      (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor kappa-B
      (NF-kappaB) activities in Caco-2 cells. Moreover, inhibitor kappaB-alpha (IkappaB
      alpha) degradation was inhibited by dioscin. Dioscin enhanced the intracellular
      concentration of MTX by down-regulating MDR1 expression through a mechanism that
      involves NF-kappaB signaling pathway inhibition in Caco-2 cells. Dioscin
      strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In
      addition, even though MTX is absorbed into the enterocytes, there was no increase
      in toxicity observed, and that, in fact, decreased toxicity was seen. 

PMID- 24680848
TI  - Effects of dual-mode non-invasive brain stimulation on motor function.
AB  - The purpose of this study was to investigate the effects of dual-mode non
      invasive brain stimulation (NBS) on motor function and cortical excitability
      using both repetitive transcranial magnetic stimulation (rTMS) and transcranial
      direct current stimulation (tDCS) over the bilateral primary motor cortices (M1s)
      of healthy individuals. Fifteen healthy right-handed volunteers (8 women; mean
      age 23.2 years) participated in this sham-controlled random-ordered crossover
      study. All of the participants received four randomly arranged dual-mode
      stimulations with a 24-h washout period: condition 1, preconditioning with
      cathodal tDCS over the left M1 followed by 10 Hz rTMS over the right M1;
      condition 2, preconditioning Lt. anodal tDCS followed by Rt. 10 Hz rTMS;
      condition 3, Lt. sham tDCS followed by Rt. 10 Hz rTMS; and condition 4, Lt. sham
      tDCS followed by Rt. sham rTMS. Corticomotor excitability and motor function were
      assessed in the left hand before and after stimulation. The motor evoked
      potential (MEP) amplitudes significantly increased after dual-mode stimulation in
      conditions 1 and 3, and significantly decreased in condition 2. The MEP latency
      became significantly shorter in condition 1. The motor function tests revealed a
      significant improvement in the Purdue pegboard test in condition 1, and in the
      box and block tests in conditions 1 and 3. The preconditioning tDCS over the
      contralateral M1 modulated the effects of subsequent rTMS on cortical
      excitability and motor function.

PMID- 24680849
TI  - Mesenchymal stromal cells integrate and form longitudinally-aligned layers when
      delivered to injured spinal cord via a novel fibrin scaffold.
AB  - Mesenchymal stromal cells (MSCs) have been shown to promote healing and
      regeneration in a number of CNS injury models and therefore there is much
      interest in the clinical use of these cells. For spinal cord injuries, a standard
      delivery method for MSCs is intraspinal injection, but this can result in
      additional injury and provides little control over how the cells integrate into
      the tissue. The present study examines the use of a novel fibrin scaffold as a
      new method of delivering MSCs to injured spinal cord. Use of the fibrin scaffold
      resulted in the formation of longitudinally-aligned layers of MSCs growing over
      the spinal cord lesion site. Host neurites were able to migrate into this MSC
      architecture and grow longitudinally. The length of the MSC bridge corresponded
      to the length of the fibrin scaffold. MSCs that were delivered via intraspinal
      injection were mainly oriented perpendicular to the plane of the spinal cord and
      remained largely restricted to the lesion site. Host neurites within the injected
      MSC graft were also oriented perpendicular to the plane of the spinal cord. 

PMID- 24680850
TI  - Inhibition of acid-sensing ion channels by chlorogenic acid in rat dorsal root
      ganglion neurons.
AB  - Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in the
      human diet. Recently, it is demonstrated to have potent antinociceptive effect.
      However, little is understood about the mechanism underlying CGA analgesia. Here,
      we have found that CGA can exert an inhibitory effect on the functional activity
      of native acid-sensing ion channels (ASICs) in rat dorsal root ganglion (DRG)
      neurons. First, CGA decreased the peak amplitude of proton-gated currents
      mediated by ASICs in a concentration-dependent manner. Second, CGA shifted the
      proton concentration-response curve downward, with a decrease of 41.76 +/- 8.65%
      in the maximum current response to protons but with no significant change in the
      pH0.5 value. Third, CGA altered acidosis-evoked membrane excitability of rat DRG
      neurons and caused a significant decrease in the amplitude of the depolarization
      and the number of action potentials induced by acid stimuli. Finally, peripheral
      administered CGA attenuated nociceptive response to intraplantar injection of
      acetic acid in rats. ASICs are distributed in peripheral sensory neurons and
      participate in nociception. Our findings CGA inhibition of native ASICs indicated
      that CGA may exert analgesic action by modulating ASICs in the primary afferent
      neurons, which revealed a novel cellular and molecular mechanism underlying CGA
      analgesia.

PMID- 24680851
TI  - Regulation of RPE barrier function by all-trans retinoic acid in myopia.
AB  - To investigate the effect of all-trans retinoic acid (atRA) on the barrier
      function of myopia retinal pigment epithelium (RPE), primary RPE cells from
      guinea pigs were cultured on the filters as monolayer and treated with 10-9 M
      atRA. Epithelial permeability was measured by transepithelial electrical
      resistance (TER) and HRP concentration, western blot was used to observe the
      expression of intercellular junction-associated proteins. Treatment of primary
      cultures of confluent myopia RPE cells with atRA resulted in a progressive
      increase in TER and a progressive decrease of HRP concentration in the
      basolateral compartment. The expression of E-cadherin, Occludin and Claudin-1
      proteins were up-regulated after treatment with atRA for 6h to 48 h. We concluded
      that atRA could promote the epithelial barrier function of myopia RPE monolayer
      possibly by regulating expression of intercellular junction-associated proteins.

PMID- 24680852
TI  - Metabotropic glutamate receptors regulate cortical gamma hyperactivities elicited
      by ketamine in rats.
AB  - Abnormalities in electroencephalogram gamma oscillations have been implicated in
      schizophrenic symptoms. N-methyl-d-aspartate (NMDA) receptor antagonists produce
      behavioral abnormalities that are similar to the symptoms of schizophrenia,
      including social and cognitive impairment, and also increase the power of
      spontaneous gamma oscillations in the frontal cortex in rodents. Both mGlu2/3
      receptor agonists and mGlu1 receptor antagonists reportedly improve behavioral
      abnormalities elicited by NMDA receptor antagonists in rodents. The present study
      evaluated the effects of an mGlu2/3 receptor agonist and an mGlu1 receptor
      antagonist on aberrant basal gamma oscillations elicited by an NMDA receptor
      antagonist, ketamine, in the rat frontal cortex. Ketamine increased spontaneous
      cortical gamma oscillations. Pretreatment with an mGlu2/3 receptor agonist, (-)-2
      oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), or an mGlu1
      receptor antagonist, (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4
      methoxycyclohexyl)-methanone (JNJ16259685), reduced the ketamine-induced basal
      gamma hyperactivity. These findings indicate that the stimulation of mGlu2/3
      receptors and the inhibition of mGlu1 receptors reverse aberrant gamma
      oscillations, and these effects may partially explain the antipsychotic-like
      properties of mGlu2/3 receptor agonists and mGlu1 receptor antagonists.

PMID- 24680853
TI  - Long-distance neural synchrony correlates with processing strategies to compare
      fractions.
AB  - Adults use different processing strategies to work with fractions. Depending on
      task requirements, they may analyze the fraction components separately
      (componential processing strategy, CPS) or consider the fraction as a whole
      (holistic processing strategy, HPS). It is so far unknown what is the brain
      coordination dynamics underlying these types of fraction processing strategies.
      To elucidate this issue, we analyzed oscillatory brain activity during a fraction
      comparison task, presenting pairs of fractions either with or without common
      components. Results show that CPS induces a left frontal-parietal alpha phase
      desynchronization after the onset of fraction pairs, while HPS induces an
      increase of phase synchrony on theta and gamma bands, over frontal and central
      parietal sites, respectively. Additionally, the HPS evokes more negative ERPs
      around 400 ms over the right frontal scalp than the CPS. This ERP activity
      correlates with the increase of Theta phase synchrony. Our results reveal the
      emergence of different functional neural networks depending on the kind of
      cognitive strategy used for processing fractions.

PMID- 24680854
TI  - Bereitschaftspotential in remitted paediatric bipolar disorder.
AB  - Bereitschaftspotential (BP) is an anticipatory slow wave in the brain that
      typically precedes a voluntary motor act and its deficit reflects abnormal motor
      preparatory processes in the brain. Although BP deficits have been consistently
      noticed in schizophrenia, similar research in depression has yielded
      contradictory results; therefore, it is unclear if motor anticipatory processes
      are actually abnormal in mood disorder. We compared both early and late BP
      between thirty remitted paediatric bipolar patients (PBD) and thirty matched
      healthy control group subjects. We did not find any evidence of BP abnormality in
      PBD, indicating normal motor preparatory processes in this condition. This
      finding is in agreement with our previous research reporting normal anticipatory
      slow waves in bipolar subjects. Future research needs to address the specificity
      of normal anticipatory slow waves in bipolar disorder, compared to other major
      Psychoses. 

PMID- 24680855
TI  - Cortical involvement in the StartReact effect.
AB  - The rapid release of prepared movements by a loud acoustic stimulus capable of
      eliciting a startle response has been termed the StartReact effect (Valls-Sole et
      al., 1999), and premotor reaction times (PMTs) of <70 ms are often observed. Two
      explanations have been given for these short latency responses. The subcortical
      storage and triggering hypothesis suggests movements that can be prepared in
      advance of a "go" signal are stored and triggered from subcortical areas by a
      startling acoustic stimulus (SAS) without cortical involvement. Alternatively, it
      has been hypothesized that the SAS can trigger movements from cortical areas
      through a faster pathway ascending from subcortical structures. Two experiments
      were designed to examine the possible role of the primary motor cortex in the
      StartReact effect. In Experiment 1, we used suprathreshold transcranial magnetic
      stimulation (TMS) during the reaction time (RT) interval to induce a cortical
      silent period in the contralateral primary motor cortex (M1). Thirteen
      participants performed 20 degrees  wrist extension movements as fast as possible
      in response to either a control stimulus (82 dB) or SAS (124 dB). PMTs for
      startle trials were faster than for control trials, while TMS significantly
      delayed movement onset compared to No TMS or Sham TMS conditions. In Experiment
      2, we examined the StartReact effect in a highly cortically represented action
      involving speech of a consonant-vowel (CV) syllable. Similar to previous work
      examining limb movements, a robust StartReact effect was found. Collectively,
      these experiments provide evidence for cortical (M1) involvement in the
      StartReact effect.

PMID- 24680856
TI  - The effects of N-acetyl-cysteine and acetyl-L-carnitine on neural survival,
      neuroinflammation and regeneration following spinal cord injury.
AB  - Traumatic spinal cord injury induces a long-standing inflammatory response in the
      spinal cord tissue, leading to a progressive apoptotic death of spinal cord
      neurons and glial cells. We have recently demonstrated that immediate treatment
      with the antioxidants N-acetyl-cysteine (NAC) and acetyl-l-carnitine (ALC)
      attenuates neuroinflammation, induces axonal sprouting, and reduces the death of
      motoneurons in the vicinity of the trauma zone 4weeks after initial trauma. The
      objective of the current study was to investigate the effects of long-term
      antioxidant treatment on the survival of descending rubrospinal neurons after
      spinal cord injury in rats. It also examines the short- and long-term effects of
      treatment on apoptosis, inflammation, and regeneration in the spinal cord trauma
      zone. Spinal cord hemisection performed at the level C3 induced a significant
      loss of rubrospinal neurons 8 weeks after injury. At 2 weeks, an increase in the
      expression of the apoptosis-associated markers BCL-2-associated X protein (BAX)
      and caspase 3, as well as the microglial cell markers OX42 and ectodermal
      dysplasia 1 (ED1), was seen in the trauma zone. After 8 weeks, an increase in
      immunostaining for OX42 and the serotonin marker 5HT was detected in the same
      area. Antioxidant therapy reduced the loss of rubrospinal neurons by
      approximately 50%. Treatment also decreased the expression of BAX, caspase 3,
      OX42 and ED1 after 2 weeks. After 8 weeks, treatment decreased immunoreactivity
      for OX42, whereas it was increased for 5HT. In conclusion, this study provides
      further insight in the effects of treatment with NAC and ALC on descending
      pathways, as well as short- and long-term effects on the spinal cord trauma zone.

PMID- 24680857
TI  - The role of TLR4-mediated PTEN/PI3K/AKT/NF-kappaB signaling pathway in
      neuroinflammation in hippocampal neurons.
AB  - This study investigated a possible role for a toll-like receptor 4 (TLR4)
      mediated PTEN/PI3K/AKT/NF-kappaB signaling pathway in neuroinflammation in rat
      hippocampal neurons. Cultured neurons were treated with lipopolysaccharide (LPS),
      a TLR4 ligand, or pre-treated with TLR4 antibodies to block TLR4 signaling.
      Neurons were also treated with dipotassium bisperoxo (pyridine-2-carboxyl)
      oxovanadate [bpV(pic)] and pyrrolidine dithiocarbamate (PDTC), selective
      inhibitors of PTEN and NF-kappaB, respectively, in the presence of LPS. The
      levels of PTEN, AKT, and their phosphorylated forms were evaluated, along with
      the nuclear localization of NF-kappaB, to assess pathway activation. The
      induction of a neuroinflammatory response was determined by measuring TNF-alpha
      and IL-1beta mRNA and protein levels. The results indicated that while LPS
      stimulation had no effect on PTEN and AKT expression, the levels of
      phosphorylated PTEN (pPTEN) decreased, while phosphorylated AKT (pAKT) levels
      increased. Moreover, LPS treatment induced the nuclear translocation of NF
      kappaB, and increased the expression and secretion of TNF-alpha and IL-1beta.
      Blocking TLR4 increased the levels of pPTEN and decreased the levels of pAKT,
      while pre-treatment with bpV(pic) led to a reduction in levels of pPTEN and pAKT.
      Furthermore, treatment with TLR4 antibody, bpV(pic), and PDTC decreased LPS
      induced nuclear translocation of NF-kappaB, and resulted in a downregulation of
      TNF-alpha and IL-1beta expression. Taken together, these results provide evidence
      for a TLR4-mediated PTEN/PI3K/AKT/NF-kappaB signaling pathway in rat hippocampal
      neurons, which is associated with the activation of a neuroinflammatory response.

PMID- 24680858
TI  - Presence, viral load and characterization of Torque teno sus viruses in liver and
      pork chop samples at retail.
AB  - Torque teno viruses (TTV) are widespread in humans, swine as well as in several
      other animal species. In market ready swine, the reported prevalence ranges
      between 11% and 100%. Through a national retail sampling plan from the Canadian
      Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) program,
      283 and 599 liver and pork chop samples, respectively, were collected over a 12
      month period from commercial establishments in 5 selected geographical regions of
      Canada to assess the presence of Torque teno sus viruses (TTSuVs) in these
      products. TTSuVs were detected in 97.9% of pork chops with viral loads ranging
      between 1*10(4) and 9.9*10(5) genomic copies (gc)/g and 98.6% of liver samples
      with viral loads ranging from 1*10(5) to 9.9*10(6) gc/g. A selection of 20
      positive samples (10 pork chop and 10 liver) from the 5 geographical regions were
      further tested for the production, of a 305bp fragment for TTSuV1 and a 253bp
      fragment for TTSuV2 in the non-coding region. TTSuV1 was present in all 10 liver
      and 10 pork chops samples while TTSuV2 was detected in 10 liver and 9 pork chop
      samples. Two different TTSuV1 sequences were simultaneously detected from 5 of 20
      samples and 2 different TTSuV2 sequences were detected from 6 of 19 samples. The
      omnipresence of TTSuVs in commercial pork samples may allow its use as a viral
      indicator to monitor the effectiveness of cleaning and disinfecting process in
      slaughtering, cutting, slicing and packaging facilities. 

PMID- 24680859
TI  - Laparoscopic-assisted versus open pancreaticoduodenectomy: early favorable
      physical quality-of-life measures.
AB  - BACKGROUND: We compared outcomes and postpancreatectomy quality of life (QOL) in
      paired cohorts of patients undergoing conventional open pancreaticoduodenectomy
      (OPD) or laparoscopic-assisted pancreaticoduodenectomy (LAPD). METHODS:
      Comparative analysis of QOL was performed in a matched cohort of 53 patients
      after OPD or LAPD between 2010 and 2013. The Medical Outcomes Study Short Form-36
      Health Survey and the Karnofsky score were used. RESULTS: Physical component
      score, mental component score, and Karnofsky scores were calculated at multiple
      time points for OPD (n = 25) and LAPD (n = 28). Operative times, complications,
      and readmission rates were equivalent. Time to starting adjuvant therapy trended
      toward clinical importance in LAPD (61 vs 110 days, P = .0878). Duration of stay
      was less in LAPD (7.10 vs 9.44 days, P = .02). LAPD had a superior QOL centered
      on functional status compared with OPD (physical component score 49.09 vs 38.4, P
      = .04; Karnofsky 92.22 vs 66.92%, P = .003). These statistical differences were
      not observed beyond 6 months. CONCLUSION: LAPD provided a more favorable QOL
      within the first 6 months and shorter length of stay compared with conventional
      OPD. LAPD may serve as an alternative operative therapy to potentially minimize
      delays in receipt of and enhance tolerability of adjuvant therapies.

PMID- 24680860
TI  - Metabolic engineering of ammonium release for nitrogen-fixing multispecies
      microbial cell-factories.
AB  - The biological nitrogen fixation carried out by some Bacteria and Archaea is one
      of the most attractive alternatives to synthetic nitrogen fertilizers. In this
      study we compared the effect of controlling the maximum activation state of the
      Azotobacter vinelandii glutamine synthase by a point mutation at the active site
      (D49S mutation) and impairing the ammonium-dependent homeostatic control of
      nitrogen-fixation genes expression by the DeltanifL mutation on ammonium release
      by the cells. Strains bearing the single D49S mutation were more efficient
      ammonium producers under carbon/energy limiting conditions and sustained
      microalgae growth at the expense of atmospheric N2 in synthetic microalgae
      bacteria consortia. Ammonium delivery by the different strains had implications
      for the microalga's cell-size distribution. It was uncovered an extensive cross
      regulation between nitrogen fixation and assimilation that extends current
      knowledge on this key metabolic pathway and might represent valuable hints for
      further improvements of versatile N2-fixing microbial-cell factories. 

PMID- 24680861
TI  - Effects of glycerol on apoptotic signaling pathways during boar spermatozoa
      cryopreservation.
AB  - Artificial insemination (AI) with post-thawed boar spermatozoa results in low
      farrowing rates and reduced litter sizes mainly due to cryoinjury or damages to
      spermatozoa during cryopreservation. Low viability and motility of post-thawed
      boar spermatozoa are highly associated with apoptosis during cryopreservation.
      Although glycerol is widely used a cryoprotectant (CPA) for boar spermatozoa
      cryopreservation, the mechanism and relationship between glycerol and apoptosis
      related gene expression needs to be clarified. In this study, we treated boar
      spermatozoa with different concentrations of glycerol in lactose egg yolk (LEY)
      extender to evaluate the apoptosis-related gene expression and protease
      activities of caspases. These results show that: (1) low concentrations of
      glycerol (2% and 3%) were more suitable for boar spermatozoa cryopreservation;
      (2) apoptosis-related genes involved in intrinsic mitochondrial and extrinsic
      death receptor apoptotic signaling pathways were widely expressed in different
      concentrations of glycerol treated boar spermatozoa; (3) there was a significant
      positive correlation (r=0.840, P=0.037) between the percentage of Annexin
      V(+)/PI(+) staining spermatozoa and caspase-6/9 protease activity. In conclusion,
      2% and 3% glycerol have the best anti-apoptotic effects, and the expression of
      Fas/FasL and Bcl-2/Bax have a strong correlation with spermatozoa parameters.

PMID- 24680862
TI  - Clearance of Pneumocystis murina infection is not dependent on MyD88.
AB  - To determine if myeloid differentiation factor 88 (MyD88), which is necessary for
      signaling by most TLRs and IL-1Rs, is necessary for control of Pneumocystis
      infection, MyD88-deficient and wild-type mice were infected with Pneumocystis by
      exposure to infected seeder mice and were followed for up to 106 days. MyD88
      deficient mice showed clearance of Pneumocystis and development of anti
      Pneumocystis antibody responses with kinetics similar to wild-type mice. Based on
      expression levels of select genes, MyD88-deficient mice developed immune
      responses similar to wild-type mice. Thus, MyD88 and the upstream pathways that
      rely on MyD88 signaling are not required for control of Pneumocystis infection.

PMID- 24680864
TI  - 25-Hydroxyvitamin D: analysis and clinical application.
AB  - 25-Hydroxyvitamin D (25-OHD) is one of the most popular tests requested by
      clinicians nowadays because in addition to bone diseases, many non-skeletal
      disorders have been suggested to be linked to vitamin D deficiency or
      insufficiency. Methodologies used in clinical laboratories include competitive
      vitamin D protein binding assays (CPBA), immunoassays, high performance liquid
      chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC
      MS/MS). In this review article, we introduce the basic metabolism and physiology
      of vitamin D, key issues in the methods for 25-OHD measurement currently used in
      most clinical laboratories, and clinical applications of 25-OHD testing. We
      conclude that although the methodologies for 25-OHD testing have improved
      significantly, considerable bias between different methods and laboratories still
      exists. Therefore, standardization of the method is critical. The optimal 25-OHD
      levels should be determined based on the standardized method. Also, more studies
      are needed to further determine the relationship between vitamin D deficiency or
      insufficiency and non-skeletal diseases as well as daily vitamin D dose
      requirement for reducing the risk of non-skeletal diseases. 

PMID- 24680863
TI  - Kidney protein profiling of Wilms' tumor patients by analysis of formalin-fixed
      paraffin-embedded tissue samples.
AB  - Wilms' tumor (nephroblastoma, WT) is the most frequent renal cancer in children.
      However, molecular details leading to WT have not been characterized sufficiently
      yet. Proteomic studies might provide new insights but are hampered by limited
      availability of fresh frozen tissue specimen. Therefore, we tested formalin-fixed
      paraffin-embedded (FFPE) tissue sections routinely collected for pathological
      inspection for their use in in-depth-proteomic analyses of WT samples in
      comparison to fresh frozen specimen. The overlap of the proteins identified was
      over 65%. Thus we used FFPE material from 7 patients for tandem mass spectrometry
      based comparison of the proteomes of WT and healthy renal tissues. We detected
      262 proteins, which were differentially expressed in tumor compared to healthy
      renal tissue. The majority of these proteins displayed lower levels in the tumor
      tissue and only 30% higher levels. For selected candidates data were confirmed by
      immunohistochemical staining. Correlation analysis of blastemal proportions in WT
      and protein intensities revealed candidates for tumor stratification. CONCLUSION:
      This proof of principle proteomic study of FFPE tissue sections from WT patients
      demonstrates that these archived tissues constitute a valuable resource for
      larger in-depth proteomic studies to identify markers to follow chemotherapy
      efficiency or for stratification of tumor subtypes.

PMID- 24680866
TI  - Methylprednisolone treatment fails to protect mice from the H5N1 influenza A
      virus-induced proinflammatory response and mortality.

PMID- 24680865
TI  - Constitutive activation of the ATM/BRCA1 pathway prevents DNA damage-induced
      apoptosis in 5-azacytidine-resistant cell lines.
AB  - 5-Azacytidine (AZA) exerts its anti-tumor effects by exerting cytotoxicity via
      its incorporation into RNA and DNA, which causes the reactivation of aberrantly
      silenced growth-regulatory genes by promoter demethylation, as well as DNA
      damage. AZA is used for patients with myelodysplastic syndrome and acute myeloid
      leukemia. However, some patients demonstrate resistance to AZA, the mechanisms of
      which are not fully elucidated. We therefore sought to better characterize the
      molecular mechanism of AZA resistance using an in vitro model of AZA resistance.
      We established AZA-resistant cell lines by exposing the human leukemia cell lines
      U937 and HL-60 to clinical concentrations of AZA, and characterized these cells.
      AZA-resistant cells showed a down-regulation of the DNMT3A protein, in
      correlation with their marked genome-wide DNA hypomethylation. Furthermore, genes
      involved in pyrimidine metabolism were down-regulated in both AZA-resistant cell
      lines; AZA sensitivity was restored by inhibition of CTP synthase. Of note is
      that the DNA damage response pathway is constitutively activated in the AZA
      resistant cell lines, but not in the parental cell lines. Inhibition of the DNA
      damage response pathway canceled the AZA resistance, in association with an
      increase in apoptotic cells. We found that the molecular mechanism underlying AZA
      resistance involves pyrimidine metabolism and the DNA damage response through ATM
      kinase. This study therefore sheds light on the mechanisms underlying AZA
      resistance, and will enable better understanding of AZA resistance in patients
      undergoing AZA treatment. 

PMID- 24680867
TI  - Spatial variability of functional brain networks in early-blind and sighted
      subjects.
AB  - To further the understanding how the human brain adapts to early-onset blindness,
      we searched in early-blind and normally-sighted subjects for functional brain
      networks showing the most and least spatial variabilities across subjects. We
      hypothesized that the functional networks compensating for early-onset blindness
      undergo cortical reorganization. To determine whether reorganization of
      functional networks affects spatial variability, we used functional magnetic
      resonance imaging to compare brain networks, derived by independent component
      analysis, of 7 early-blind and 7 sighted subjects while they rested or listened
      to an audio drama. In both conditions, the blind compared with sighted subjects
      showed more spatial variability in a bilateral parietal network (comprising the
      inferior parietal and angular gyri and precuneus) and in a bilateral auditory
      network (comprising the superior temporal gyri). In contrast, a vision-related
      left-hemisphere-lateralized occipital network (comprising the superior, middle
      and inferior occipital gyri, fusiform and lingual gyri, and the calcarine sulcus)
      was less variable in blind than sighted subjects. Another visual network and a
      tactile network were spatially more variable in the blind than sighted subjects
      in one condition. We contemplate whether our results on inter-subject spatial
      variability of brain networks are related to experience-dependent brain
      plasticity, and we suggest that auditory and parietal networks undergo a stronger
      experience-dependent reorganization in the early-blind than sighted subjects
      while the opposite is true for the vision-related occipital network. 

PMID- 24680868
TI  - Automatic anatomical labeling of the complete cerebral vasculature in mouse
      models.
AB  - Study of cerebral vascular structure broadens our understanding of underlying
      variations, such as pathologies that can lead to cerebrovascular disorders. The
      development of high resolution 3D imaging modalities has provided us with the raw
      material to study the blood vessels in small animals such as mice. However, the
      high complexity and 3D nature of the cerebral vasculature make comparison and
      analysis of the vessels difficult, time-consuming and laborious. Here we present
      a framework for automated segmentation and recognition of the cerebral vessels in
      high resolution 3D images that addresses this need. The vasculature is segmented
      by following vessel center lines starting from automatically generated seeds and
      the vascular structure is represented as a graph. Each vessel segment is
      represented as an edge in the graph and has local features such as length,
      diameter, and direction, and relational features representing the connectivity of
      the vessel segments. Using these features, each edge in the graph is
      automatically labeled with its anatomical name using a stochastic relaxation
      algorithm. We have validated our method on micro-CT images of C57Bl/6J mice. A
      leave-one-out test performed on the labeled data set demonstrated the recognition
      rate for all vessels including major named vessels and their minor branches to be
      >75%. This automatic segmentation and recognition methods facilitate the
      comparison of blood vessels in large populations of subjects and allow us to
      study cerebrovascular variations. 

PMID- 24680869
TI  - Restricted Boltzmann machines for neuroimaging: an application in identifying
      intrinsic networks.
AB  - Matrix factorization models are the current dominant approach for resolving
      meaningful data-driven features in neuroimaging data. Among them, independent
      component analysis (ICA) is arguably the most widely used for identifying
      functional networks, and its success has led to a number of versatile extensions
      to group and multimodal data. However there are indications that ICA may have
      reached a limit in flexibility and representational capacity, as the majority of
      such extensions are case-driven, custom-made solutions that are still contained
      within the class of mixture models. In this work, we seek out a principled and
      naturally extensible approach and consider a probabilistic model known as a
      restricted Boltzmann machine (RBM). An RBM separates linear factors from
      functional brain imaging data by fitting a probability distribution model to the
      data. Importantly, the solution can be used as a building block for more complex
      (deep) models, making it naturally suitable for hierarchical and multimodal
      extensions that are not easily captured when using linear factorizations alone.
      We investigate the capability of RBMs to identify intrinsic networks and compare
      its performance to that of well-known linear mixture models, in particular ICA.
      Using synthetic and real task fMRI data, we show that RBMs can be used to
      identify networks and their temporal activations with accuracy that is equal or
      greater than that of factorization models. The demonstrated effectiveness of RBMs
      supports its use as a building block for deeper models, a significant prospect
      for future neuroimaging research. 

PMID- 24680870
TI  - Assessing white matter microstructure of the newborn with multi-shell diffusion
      MRI and biophysical compartment models.
AB  - Brain white matter connections have become a focus of major interest with
      important maturational processes occurring in newborns. To study the complex
      microstructural developmental changes in-vivo, it is imperative that non-invasive
      neuroimaging approaches are developed for this age-group. Multi-b-value diffusion
      weighted imaging data were acquired in 13 newborns, and the biophysical
      compartment diffusion models CHARMED-light and NODDI, providing new
      microstructural parameters such as intra-neurite volume fraction (nuin) and
      neurite orientation dispersion index (ODI), were developed for newborn data.
      Comparative analysis was performed and twenty ROIs in the white matter were
      investigated. Diffusion tensor imaging and both biophysical compartment models
      highlighted the compact and oriented structure of the corpus-callosum with the
      highest FA and nuin values and the smallest ODI values. We could clearly
      differentiate, using the FA, nuin and ODI, the posterior and anterior internal
      capsule representing similar cellular structure but with different maturation
      (i.e. partially myelinated and absence of myelin, respectively). Late maturing
      regions (external capsule and periventricular crossroads of pathways) had lower
      nuin values, but displayed significant differences in ODI. The compartmented
      models CHARMED-light and NODDI bring new indices corroborating the cellular
      architectures, with the lowest nuin, reflecting the late maturation of areas with
      thin non-myelinated fibers, and with highest ODI indicating the presence of fiber
      crossings and fanning. The application of biophysical compartment diffusion
      models adds new insights to the brain white matter development in vivo. 

PMID- 24680871
TI  - Anti-inflammatory effect of Marchantin M contributes to sensitization of prostate
      cancer cells to docetaxel.
AB  - As pro-inflammatory cytokines and chemokines contribute to the malignancy of many
      types of human cancer, we examined the anti-inflammatory effect of bisbibenzyls,
      a diverse bioactive group of naturally occurring compounds. Marchantin M (Mar M)
      was identified through a screening process of these compounds as a potent anti
      inflammatory agent based on its capacity to inhibit LPS-induced IL6, IL1beta and
      CCL2 expression in HUVECs and PBMCs without affecting cell proliferation. Since
      Mar M has been found to exhibit anticancer activity, we observed that Mar M
      treatment also resulted in decreases in the expressions of IL6, IL1beta and
      TNFalpha in metastatic prostate cancer (PCa) cells. This effect was further
      confirmed in other cancer cell lines that express high level of pro-inflammatory
      cytokines. Furthermore, inactivation of NF-kappaB, a critical transcription
      factor controlling many pro-inflammatory cytokine expressions, was observed in
      Mar M-treated PCa cells as evidenced by decreased phosphor-p65 and subsequently
      phosphor-STAT3. Mar M also suppressed phosphorylation of IKBalpha, an inhibitor
      of NF-kappaB in the cytosol. However, reduced phosphor-p65 by Mar M was slightly
      increased when knockdown of IKBalpha, suggesting that Mar M may target upstream
      molecules of IKBalpha/NF-kappaB signaling. Finally, treatment with Mar M resulted
      in more enhanced-sensitivity of PCa cells to docetaxel-induced apoptosis than
      that of the IL6 blocking. Our study demonstrates the potential of the anti
      inflammatory agent Mar M as an adjuvant to improve the efficacy of traditional
      anticancer agents such as docetaxel. 

PMID- 24680872
TI  - Prevalence and correlates of binge eating in seasonal affective disorder.
AB  - Eating pathology in Seasonal Affective Disorder (SAD) may be more severe than
      hyperphagia during winter. Although research has documented elevated rates of
      subclinical binge eating in women with SAD, the prevalence and correlates of
      binge eating disorder (BED) in SAD remain largely uncharacterized. We examined
      the prevalence and correlates of binge eating, weekly binge eating with distress,
      and BED as defined by the DSM-IV-TR in SAD. We also tested whether binge eating
      exhibits a seasonal pattern among individuals with BED. Two samples were combined
      to form a sample of individuals with SAD (N=112). A third sample included non
      depressed adults with clinical (n=12) and subclinical (n=11) BED. All
      participants completed the Questionnaire of Eating and Weight Patterns-Revised
      (QEWP-R) and modified Seasonal Pattern Assessment Questionnaire (M-SPAQ). In the
      SAD sample, 26.5% reported binge eating, 11.6% met criteria for weekly binge
      eating with distress, and 8.9% met criteria for BED. Atypical symptom severity
      predicted binge eating and BED. In the BED sample, 30% endorsed seasonal
      worsening of mood, and 26% reported a winter pattern of binge eating. The
      spectrum of eating pathology in SAD includes symptoms of BED, which are
      associated with atypical depression symptoms, but typical depression symptoms. 

PMID- 24680873
TI  - Attachment anxiety moderates the relationship between childhood maltreatment and
      attention bias for emotion in adults.
AB  - Research indicates that some individuals who were maltreated in childhood
      demonstrate biases in social information processing. However, the mechanisms
      through which these biases develop remain unclear-one possible mechanism is via
      attachment-related processes. Childhood maltreatment increases risk for insecure
      attachment. The internal working models of self and others associated with
      insecure attachment may impact the processing of socially relevant information,
      particularly emotion conveyed in facial expressions. We investigated associations
      among child abuse, attachment anxiety and avoidance, and attention biases for
      emotion in an adult population. Specifically, we examined how self-reported
      attachment influences the relationship between childhood abuse and attention bias
      for emotion. A dot probe task consisting of happy, threatening, and neutral
      female facial stimuli was used to assess possible biases in attention for
      socially relevant stimuli. Our findings indicate that attachment anxiety
      moderated the relationship between maltreatment and attention bias for happy
      emotion; among individuals with a child abuse history, attachment anxiety
      significantly predicted an attention bias away from happy facial stimuli. 

PMID- 24680874
TI  - Screening for personality disorder in drug and alcohol dependence.
AB  - Comorbidity of personality disorders in addiction is common, and there is a need
      for efficient detection methods. This study describes the use of two quick
      screening instruments: the self-reported versions of the Iowa Personality
      Disorder Screen (IPDS-SR) and the Standardised Assessment of Personality
      Abbreviated Scale (SAPAS-SR). The sample included 53 inpatients dependent on
      alcohol and/or drugs, with a 42% prevalence of any DSM-IV personality disorder.
      The Personality Assessment Schedule (PAS) was used as gold standard. Receiver
      Operant-Characteristic (ROC) was used for analysis. The Area Under the Curve for
      the IPDS-SR was 0.84 (95% CI 0.72-0.93) and for the SAPAS-SR was 0.82 (95% CI
      0.70-0.93). An IPDS-SR score of 5 or more correctly classified 77.4% of patients,
      with a sensitivity of 86.4% and a specificity of 71%. A SAPAS-SR score of 4 or
      more correctly classified 73.6% of patients, with a sensitivity of 81.8% and a
      specificity of 67.7%. Both instruments were quick, easy to administer, and
      acceptable to use by this population. They can be implemented in routine clinical
      practice in busy substance misuse departments. However further research into the
      implications of positive screenings is required. 

PMID- 24680875
TI  - Is change in global self-rated health associated with change in affiliation with
      a primary care provider? Findings from a longitudinal study from New Zealand.
AB  - AIMS: To investigate the association of self-rated health and affiliation with a
      primary care provider (PCP) in New Zealand. METHODS: We used data from a New
      Zealand panel study of 22,000 adults. The main exposure was self-rated health,
      and the main outcome measure was affiliation with a PCP. Fixed effects
      conditional logistic models were used to control for observed time-varying and
      unobserved time-invariant confounding. RESULTS: In any given wave, the odds of
      being affiliated with a PCP were higher for those in good and fair/poor health
      relative to those in excellent health. While affiliation for Europeans increased
      as reported health declined, the odds of being affiliated were lower for Maori
      respondents reporting very good or good health relative to those in excellent
      health. No significant differences in the association by age or gender were
      observed. CONCLUSIONS: Our data support the hypothesis that those in poorer
      health are more likely to be affiliated with a PCP. Variations in affiliation for
      Maori could arise for several reasons, including differences in care-seeking
      behaviour and perceived need of care. It may also mean that the message about the
      benefits of primary health care is not getting through equally to all population
      groups.

PMID- 24680876
TI  - Perioperative nurses' experiences of communication in a multicultural operating
      theatre: A qualitative study.
AB  - AIM: To explore the lived experiences of perioperative nurses in a multicultural
      operating theatre in Melbourne, Australia. BACKGROUND: Multiculturalism has
      become the norm in the health workforce of several developed countries due mostly
      to immigration. Within an operating theatre setting where good communication is
      paramount, the presence of nurses and doctors from multiple cultures and
      different training backgrounds could pose a major challenge. METHOD: Using a
      qualitative research methodology underpinned by phenomenology, we interviewed
      fourteen nurses from different sections of an operating theatre. RESULTS: From
      the lived experiences of the participants, difficulties in communication emerged
      as the major theme. Difficulties in communication affected patient care and the
      working atmosphere. In addition, social integration appeared to improve
      communication. CONCLUSIONS: Addressing the needs of patients from culturally and
      linguistically diverse backgrounds in the operating theatre continues to be
      challenging. However, developing a sense of camaraderie and fostering good
      relationships between staff through regular social gatherings can improve
      communication and the working atmosphere.

PMID- 24680877
TI  - Impaired body balance control in adults with strabismus.
AB  - Previous studies revealed that people with binocular vision disorders have poor
      postural stability. However, most of the research was performed only on children
      and under binocular viewing condition, that could negatively affect the results.
      The aim of the current study was to investigate the influence of extra-ocular
      proprioceptive signals on postural stability in young adults with binocular
      vision disorders. Moreover, additional mental task was introduced to detect any
      postural compensation which could possibly hide the real influence of afferent
      extra-ocular signals. 21 Subjects, aged 18-45 yrs, with horizontal strabismus,
      were qualified to binocular vision disorders (BVD) group. 41 subjects, aged 19-45
      yrs, with no strabismus formed the normal binocular vision (NBV) group.
      Posturography data were collected in 2 separate parts: (1) quiet standing (Single
      Task), and (2) performance of a mental task while standing (Dual-Task). Each part
      consisted of three 60-s viewing conditions, with: (1) dominant/fellow eye (DE),
      (2) non-dominant/strabismic eye (NDE), and with (3) both eyes closed (EC).
      Subjects were looking at X located at the distance of 150 cm. Generally, BVD
      group showed elevated body balance during quiet stance compared to NBV group.
      Interestingly, better stabilization in BVD group occurred under NDE viewing.
      Surprisingly, additional mental task improved the postural stability in BVD group
      almost to the level of NBV group. These findings emphasize the role of the eye
      muscle signals in postural control and suggest that suitable vision therapy can
      be the appropriate way to improve body balance/motor functions in people with
      binocular vision disorders.

PMID- 24680879
TI  - Lifetime of high-order thickness resonances of thin silicon membranes.
AB  - Femtosecond laser pulses are used to excite and probe high-order longitudinal
      thickness resonances at a frequency of ~270 GHz in suspended Si membranes with
      thickness ranging from 0.4 to 15 MUm. The measured acoustic lifetime scales
      linearly with the membrane thickness and is shown to be controlled by the surface
      specularity which correlates with roughness characterized by atomic force
      microscopy. Observed Q-factor values up to 2400 at room temperature result from
      the existence of a local maximum of the material Q in the sub-THz range. However,
      surface specularity would need to be improved over measured values of ~0.5 in
      order to achieve high Q values in nanoscale devices. The results support the
      validity of the diffuse boundary scattering model in analyzing thermal transport
      in thin Si membranes.

PMID- 24680880
TI  - Tandem shock waves to enhance genetic transformation of Aspergillus niger.
AB  - Filamentous fungi are used in several industries and in academia to produce
      antibiotics, metabolites, proteins and pharmaceutical compounds. The development
      of valuable strains usually requires the insertion of recombinant
      deoxyribonucleic acid; however, the protocols to transfer DNA to fungal cells are
      highly inefficient. Recently, underwater shock waves were successfully used to
      genetically transform filamentous fungi. The purpose of this research was to
      demonstrate that the efficiency of transformation can be improved significantly
      by enhancing acoustic cavitation using tandem (dual-pulse) shock waves. Results
      revealed that tandem pressure pulses, generated at a delay of 300 MUs, increased
      the transformation efficiency of Aspergillus niger up to 84% in comparison with
      conventional (single-pulse) shock waves. This methodology may also be useful to
      obtain new strains required in basic research and biotechnology.

PMID- 24680881
TI  - The high-mobility group I-Y transcription factor is involved in cerebral ischemia
      and modulates the expression of angiogenic proteins.
AB  - The present study aims to identify transcription factors (TFs) contributing to
      angiogenesis, a mechanism involved in giving plasticity to the brain, as
      potential therapeutic targets after cerebral ischemia. The promoter sequences
      from candidate genes involved in angiogenesis were submitted to a comparative
      analysis by bioinformatics software. High-mobility group I-Y protein (HMGIY) TF
      characterization in a rat permanent focal cerebral ischemia model was performed
      by quantitative real time polymerase chain reaction and Western blot for the TF
      expression profile study. The TF functional study was carried out using a TF-TF
      interaction array and gene silencing by siRNA in rat brain microvascular
      endothelial cells. The results showed that the promoters shared a common TF
      binding site for HMGIY. The expression profile analysis in ischemic rat brain
      showed an increase in HMGIY mRNA in the acute phase and a progressive
      overexpression of protein over time post-ischemia. The interaction array analysis
      revealed that ischemia promotes the interaction of HMGIY with TFs involved in
      different cerebral plasticity processes. In vitro knockdown studies showed that
      angiopoietin 1 and vascular endothelial growth factor expression is controlled by
      HMGIY and that this TF is involved in cell survival in brain endothelial cells.
      These findings suggest that HMGIY is a potential therapeutic target that could
      promote brain repair functions after stroke. 

PMID- 24680878
TI  - DNA-PK: a dynamic enzyme in a versatile DSB repair pathway.
AB  - DNA double stranded breaks (DSBs) are the most cytoxic DNA lesion as the
      inability to properly repair them can lead to genomic instability and
      tumorigenesis. The prominent DSB repair pathway in humans is non-homologous end
      joining (NHEJ). In the simplest sense, NHEJ mediates the direct re-ligation of
      the broken DNA molecule. However, NHEJ is a complex and versatile process that
      can repair DSBs with a variety of damages and ends via the utilization of a
      significant number of proteins. In this review we will describe the important
      factors and mechanisms modulating NHEJ with emphasis given to the versatility of
      this repair process and the DNA-PK complex. 

PMID- 24680882
TI  - Effects of an early experience of reward through maternal contact or its denial
      on the dopaminergic system of the rat brain.
AB  - The mesolimbic/mesocortical dopaminergic pathway plays a pivotal role in the
      reward system. During the neonatal period the mother is the main source of
      rewarding stimuli. We have developed an experimental model in which rat pups
      learn a T-maze during the neonatal period (postnatal day (PND) 10-13) using
      contact with the mother as the reward. One group of animals is allowed contact
      with the mother (receipt of expected reward, RER) while the other was denied
      (denial of expected reward, DER). We determined the effects of these two early
      experiences in the prefrontal cortex (PFC) and the nucleus accumbens (nAc), the
      levels of dopamine (DA) and its metabolites [3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA)] by high-performance liquid chromatography
      and those of D1 and D2 receptors by autoradiographic in vitro binding both on PND
      13 and in adulthood. On PND13, 2h after the end of training, the RER experience
      resulted in higher DA, HVA and D1 receptor levels in the nAc, while the DER in
      lower DA and its metabolites (DOPAC and HVA) in the PFC. These results could be
      related to the reward the RER pups received through the contact with their
      mother. The RER and DER early experience had long-term sex-dependent effects: The
      RER-induced activation of the dopaminergic system in the nAc was also evident in
      adult female rats. In contrast, adult DER males, similar to PND13 animals, had
      reduced dopamine in the PFC. Our results document that early experiences, a key
      determinant of adult brain function, affect the dopaminergic system which is
      disturbed in many psychiatric diseases. 

PMID- 24680883
TI  - The induction of long-term potentiation in spinal dorsal horn after peripheral
      nociceptive stimulation and contribution of spinal TRPV1 in rats.
AB  - During chronic pain states, peripheral nociceptive stimulation can induce long
      term potentiation (LTP) in the spinal dorsal horn, but it is not clear how
      quickly spinal LTP develops after peripheral noxious stimulation. Furthermore,
      transient receptor potential vanilloid type 1 (TRPV1) receptors are abundant in
      spinal cord dorsal horn, especially in the superficial layers, and are thought to
      be involved in synaptic plasticity. In this study, we investigated the time frame
      of LTP induction after inflammatory insult and electrical stimulation and the
      involvement of TRPV1 receptors. By using extracellular recordings of C-fiber
      evoked field potentials in the superficial spinal dorsal horn and teased fiber
      recording in vivo, we found that subcutaneous injection of complete Freund's
      adjuvant (CFA) or 5% formalin induced low-frequency, irregular discharges of C
      fibers and LTP of the C-fiber-evoked field potentials in the spinal dorsal horn
      within 3h. Topical application of the TRPV1 receptor antagonist capsazepine onto
      the spinal cord inhibited the induction of spinal LTP by CFA or formalin.
      Furthermore, capsazepine and another TRPV1 antagonist, (E)-3-(4-t-butylphenyl)-N
      (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide, partially or completely blocked
      the LTP induced by conditioning stimulation with high- and low-frequency
      electrical stimulation. These results suggest that acute peripheral inflammatory
      stimulation by CFA or 5% formalin can induce spinal LTP very early after
      stimulation onset and that TRPV1 receptors in the spinal dorsal horn might
      contribute to this LTP induction. 

PMID- 24680884
TI  - Estradiol rapidly modulates odor responses in mouse vomeronasal sensory neurons.
AB  - In rodents, many social behaviors are driven by the sense of smell. The
      vomeronasal organ (VNO), part of the accessory olfactory system mediates many of
      these chemically driven behaviors. The VNO is heavily vascularized, and is
      readily accessible to circulating peptide or steroid hormones. Potentially, this
      allows circulating hormones to alter behavior through modulating the output of
      the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs).
      Based on this, we hypothesized that steroid hormones, in particular 17beta
      estradiol, would modulate activity of VSNs. In this paper, we show that the
      estrogen receptors, GPR30 and ERalpha, were present in VSNs and that estradiol
      may be synthesized locally in the VNO. Our results also showed that 17beta
      estradiol decreased responses of isolated VSNs to dilute urine, a potent natural
      stimulus, with respect to current amplitudes and depolarization. Further, 17beta
      estradiol increased the latency of the first action potential (AP) and the AP
      amplitude. Additionally, calcium responses to sulfated steroids (present in the
      low molecular weight fraction of urine) that act as ligands for apical
      vomeronasal receptors were decreased by 17beta-estradiol. In conclusion, we show
      that estradiol modulates odorant responses mediated by VSNs and hence paves the
      way for future studies to better understand the mechanisms by which odorant
      mediated behavior is altered by endocrine status of the animal. 

PMID- 24680885
TI  - Toward exact number: young children use one-to-one correspondence to measure set
      identity but not numerical equality.
AB  - Exact integer concepts are fundamental to a wide array of human activities, but
      their origins are obscure. Some have proposed that children are endowed with a
      system of natural number concepts, whereas others have argued that children
      construct these concepts by mastering verbal counting or other numeric symbols.
      This debate remains unresolved, because it is difficult to test children's
      mastery of the logic of integer concepts without using symbols to enumerate large
      sets, and the symbols themselves could be a source of difficulty for children.
      Here, we introduce a new method, focusing on large quantities and avoiding the
      use of words or other symbols for numbers, to study children's understanding of
      an essential property underlying integer concepts: the relation of exact
      numerical equality. Children aged 32-36 months, who possessed no symbols for
      exact numbers beyond 4, were given one-to-one correspondence cues to help them
      track a set of puppets, and their enumeration of the set was assessed by a non
      verbal manual search task. Children used one-to-one correspondence relations to
      reconstruct exact quantities in sets of 5 or 6 objects, as long as the elements
      forming the sets remained the same individuals. In contrast, they failed to track
      exact quantities when one element was added, removed, or substituted for another.
      These results suggest an alternative to both nativist and symbol-based
      constructivist theories of the development of natural number concepts: Before
      learning symbols for exact numbers, children have a partial understanding of the
      properties of exact numbers.

PMID- 24680886
TI  - Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model.
AB  - Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease,
      characterized by ataxia, intellectual disability, epilepsy, and premature death.
      In the majority of cases, PMD is caused by duplication of PLP1 that is expressed
      in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is
      presently no curative therapy for PMD. We used a Plp1 transgenic PMD mouse model
      to test the therapeutic effect of Lonaprisan, an antagonist of the nuclear
      progesterone receptor, in lowering Plp1 mRNA overexpression. We applied placebo
      controlled Lonaprisan therapy to PMD mice for 10 weeks and performed the grid
      slip analysis to assess the clinical phenotype. Additionally, mRNA expression and
      protein accumulation as well as histological analysis of the central nervous
      system were performed. Although Plp1 mRNA levels are increased 1.8-fold in PMD
      mice compared to wild-type controls, daily Lonaprisan treatment reduced
      overexpression at the RNA level to about 1.5-fold, which was sufficient to
      significantly improve the poor motor phenotype. Electron microscopy confirmed a
      25% increase in the number of myelinated axons in the corticospinal tract when
      compared to untreated PMD mice. Microarray analysis revealed the upregulation of
      proapoptotic genes in PMD mice that could be partially rescued by Lonaprisan
      treatment, which also reduced microgliosis, astrogliosis, and lymphocyte
      infiltration.

PMID- 24680887
TI  - Whole-exome sequencing identifies KIZ as a ciliary gene associated with autosomal
      recessive rod-cone dystrophy.
AB  - Rod-cone dystrophy (RCD), also known as retinitis pigmentosa, is a progressive
      inherited retinal disorder characterized by photoreceptor cell death and genetic
      heterogeneity. Mutations in many genes have been implicated in the
      pathophysiology of RCD, but several others remain to be identified. Herein, we
      applied whole-exome sequencing to a consanguineous family with one subject
      affected with RCD and identified a homozygous nonsense mutation, c.226C>T
      (p.Arg76(*)), in KIZ, which encodes centrosomal protein kizuna. Subsequent Sanger
      sequencing of 340 unrelated individuals with sporadic and autosomal-recessive RCD
      identified two other subjects carrying pathogenic variants in KIZ: one with the
      same homozygous nonsense mutation (c.226C>T [p.Arg76(*)]) and another with
      compound-heterozygous mutations c.119_122delAACT (p.Lys40Ilefs(*)14) and c.52G>T
      (p.Glu18(*)). Transcriptomic analysis in mice detected mRNA levels of the mouse
      ortholog (Plk1s1) in rod photoreceptors, as well as its decreased expression when
      photoreceptors degenerated in rd1 mice. The presence of the human KIZ transcript
      was confirmed by quantitative RT-PCR in the retina, the retinal pigment
      epithelium, fibroblasts, and whole-blood cells (highest expression was in the
      retina). RNA in situ hybridization demonstrated the presence of Plk1s1 mRNA in
      the outer nuclear layer of the mouse retina. Immunohistology revealed KIZ
      localization at the basal body of the cilia in human fibroblasts, thus shedding
      light on another ciliary protein implicated in autosomal-recessive RCD. 

PMID- 24680888
TI  - Antisense oligonucleotide-based therapy in human erythropoietic protoporphyria.
AB  - In 90% of people with erythropoietic protoporphyria (EPP), the disease results
      from the inheritance of a common hypomorphic FECH allele, encoding
      ferrochelatase, in trans to a private deleterious FECH mutation. The activity of
      the resulting FECH enzyme falls below the critical threshold of 35%, leading to
      the accumulation of free protoporphyrin IX (PPIX) in bone marrow erythroblasts
      and in red cells. The mechanism of low expression involves a biallelic
      polymorphism (c.315-48T>C) localized in intron 3. The 315-48C allele increases
      usage of the 3' cryptic splice site between exons 3 and 4, resulting in the
      transcription of an unstable mRNA with a premature stop codon, reducing the
      abundance of wild-type FECH mRNA, and finally reducing FECH activity. Through a
      candidate-sequence approach and an antisense-oligonucleotide-tiling method, we
      identified a sequence that, when targeted by an antisense oligonucleotide (ASO
      V1), prevented usage of the cryptic splice site. In lymphoblastoid cell lines
      derived from symptomatic EPP subjects, transfection of ASO-V1 reduced the usage
      of the cryptic splice site and efficiently redirected the splicing of intron 3
      toward the physiological acceptor site, thereby increasing the amount of
      functional FECH mRNA. Moreover, the administration of ASO-V1 into developing
      human erythroblasts from an overtly EPP subject markedly increased the production
      of WT FECH mRNA and reduced the accumulation of PPIX to a level similar to that
      measured in asymptomatic EPP subjects. Thus, EPP is a paradigmatic Mendelian
      disease in which the in vivo correction of a common single splicing defect would
      improve the condition of most affected individuals.

PMID- 24680889
TI  - De novo loss-of-function mutations in SETD5, encoding a methyltransferase in a
      3p25 microdeletion syndrome critical region, cause intellectual disability.
AB  - To identify further Mendelian causes of intellectual disability (ID), we screened
      a cohort of 996 individuals with ID for variants in 565 known or candidate genes
      by using a targeted next-generation sequencing approach. Seven loss-of-function
      (LoF) mutations-four nonsense (c.1195A>T [p.Lys399(*)], c.1333C>T [p.Arg445(*)],
      c.1866C>G [p.Tyr622(*)], and c.3001C>T [p.Arg1001(*)]) and three frameshift
      (c.2177_2178del [p.Thr726Asnfs(*)39], c.3771dup [p.Ser1258Glufs(*)65], and
      c.3856del [p.Ser1286Leufs(*)84])-were identified in SETD5, a gene predicted to
      encode a methyltransferase. All mutations were compatible with de novo dominant
      inheritance. The affected individuals had moderate to severe ID with additional
      variable features of brachycephaly; a prominent high forehead with synophrys or
      striking full and broad eyebrows; a long, thin, and tubular nose; long, narrow
      upslanting palpebral fissures; and large, fleshy low-set ears. Skeletal
      anomalies, including significant leg-length discrepancy, were a frequent finding
      in two individuals. Congenital heart defects, inguinal hernia, or hypospadias
      were also reported. Behavioral problems, including obsessive-compulsive disorder,
      hand flapping with ritualized behavior, and autism, were prominent features.
      SETD5 lies within the critical interval for 3p25 microdeletion syndrome. The
      individuals with SETD5 mutations showed phenotypic similarity to those previously
      reported with a deletion in 3p25, and thus loss of SETD5 might be sufficient to
      account for many of the clinical features observed in this condition. Our
      findings add to the growing evidence that mutations in genes encoding
      methyltransferases regulating histone modification are important causes of ID.
      This analysis provides sufficient evidence that rare de novo LoF mutations in
      SETD5 are a relatively frequent (0.7%) cause of ID.

PMID- 24680890
TI  - Detection of cerebral arterial gas embolism using regional cerebral oxygen
      saturation, quantitative electroencephalography, and brain oxygen tension in the
      swine.
AB  - BACKGROUND: Cerebral air emboli occur as a complication of invasive medical
      procedures. The sensitivity of cerebral monitoring methods for the detection of
      air emboli is not known. This study investigates the utility of
      electroencephalography and non-invasively measured cerebral oxygen saturation in
      the detection of intracerebrovascular air. NEW METHOD: In 12 pigs oxygen
      saturation was continuously measured using transcranial near-infrared
      spectroscopy and oxygen tension was continuously measured using intraparenchymal
      probes. Additionally, quantitative electroencephalography and microdialysis were
      performed. Doses of 0.2, 0.4, 0.8, and 1.6 ml of air were injected into the
      cerebral arterial vasculature through a catheter. RESULTS: Oxygen saturation and
      electroencephalography both reacted almost instantaneously on the air emboli, but
      were less sensitive than the intraparenchymal oxygen tension. There was
      reasonable correlation (rho ranging from 0.417 to 0.898) between oxygen
      saturation, oxygen tension, electroencephalography and microdialysis values.
      COMPARISON WITH EXISTING METHODS: Our study is the first to demonstrate the
      effects of cerebral air emboli using multimodal monitoring, specifically on
      oxygen saturation as measured using near-infrared spectroscopy. CONCLUSIONS: Our
      results show that non-invasively measured oxygen saturation and quantitative
      electroencephalography can detect the local effects of air emboli on cerebral
      oxygenation, but with reduced sensitivity as compared to intraparenchymal oxygen
      tension. Prospective human studies using multimodal monitoring incorporating
      electroencephalography and oxygen saturation should be performed.

PMID- 24680891
TI  - 15-Deoxy-Delta12,14-prostaglandin J2 induces PPARgamma- and p53-independent
      apoptosis in rabbit synovial cells.
AB  - A ligand of peroxisome proliferator-activated receptor gamma (PPARgamma), 15
      deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) induces apoptosis in various
      cells. However, the mechanism appears to be complex and cell-type specific. We
      investigated the mechanism of 15d-PGJ2-induced apoptosis of rabbit synovial
      cells. Exposure to 15d-PGJ2 resulted in DNA fragmentation accompanied by caspase
      3 and -9 activations in the cells, suggesting occurrence of mitochondria-mediated
      apoptosis. Although the exposure also induced remarkable increase in p53 protein,
      its transcriptional activity was rather reduced, suggesting non-necessity of p53
      in 15d-PGJ2-induced apoptosis. Covalent binding of 15d-PGJ2 to cellular proteins
      including p53 resulted in their insolubilization. N-acetylcysteine inhibited not
      only the 15d-PGJ2-induced apoptotic events but also the protein insolubilizations
      via its interaction with 15d-PGJ2. The studies using a PPARgamma-agonist and 
      antagonist showed noninvolvement of PPARgamma in 15d-PGJ2-induced apoptosis. The
      pre-exposure to pro-inflammatory cytokines did not affect the cytotoxicity of 15d
      PGJ2 in synovial cells. Taken together, these results show that 15d-PGJ2 induces
      a mitochondria-mediated apoptotic pathway in p53- and PPARgamma-independent
      manners. 

PMID- 24680893
TI  - Auto and cross regulatory elements control Onecut expression in the ascidian
      nervous system.
AB  - The expression pattern of Onecut genes in the central and peripheral nervous
      systems is highly conserved in invertebrates and vertebrates but the regulatory
      networks in which they are involved are still largely unknown. The presence of
      three gene copies in vertebrates has revealed the functional roles of the Onecut
      genes in liver, pancreas and some populations of motor neurons. Urochordates have
      only one Onecut gene and are the closest living relatives of vertebrates and thus
      represent a good model system to understand its regulatory network and
      involvement in nervous system formation. In order to define the Onecut genetic
      cascade, we extensively characterized the Onecut upstream cis-regulatory DNA in
      the ascidian Ciona intestinalis. Electroporation experiments using a 2.5kb
      genomic fragment and of a series of deletion constructs identified a small region
      of 262bp able to reproduce most of the Onecut expression profile during embryonic
      development. Further analyses, both bioinformatic and in vivo using transient
      transgenes, permitted the identification of transcription factors responsible for
      Onecut endogenous expression. We provide evidence that Neurogenin is a direct
      activator of Onecut and that an autoregulatory loop is responsible for the
      maintenance of its expression. Furthermore, for the first time we propose the
      existence of a direct connection among Neurogenin, Onecut and Rx transcription
      factors in photoreceptor cell formation. 

PMID- 24680892
TI  - AcvR1-mediated BMP signaling in second heart field is required for arterial pole
      development: implications for myocardial differentiation and regional identity.
AB  - BMP signaling plays an essential role in second heart field-derived heart and
      arterial trunk development, including myocardial differentiation, right
      ventricular growth, and interventricular, outflow tract and aortico-pulmonary
      septation. It is mediated by a number of different BMP ligands, and receptors,
      many of which are present simultaneously. The mechanisms by which they regulate
      morphogenetic events and degree of redundancy amongst them have still to be
      elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in
      anterior second heart field-derived cell development, and compared it with that
      of BmpR1a. By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1
      plays an essential role in arterial pole morphogenesis, identifying defects in
      outflow tract wall and cushion morphology that preceded a spectrum of septation
      defects from double outlet right ventricle to common arterial trunk in mutants.
      Its absence caused dysregulation in gene expression important for myocardial
      differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2).
      Although these defects resemble to some degree those in the equivalent Bmpr1a
      mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1
      locus only partially restored septation in Acvr1 mutants. These data show that
      both BmpR1a and AcvR1 are needed for normal heart development, in which they play
      some non-redundant roles, and refine our understanding of the genetic and
      morphogenetic processes underlying Bmp-mediated heart development important in
      human congenital heart disease. 

PMID- 24680894
TI  - Molecular mechanisms and potentials for differentiating inner ear stem cells into
      sensory hair cells.
AB  - In mammals, hair cells may be damaged or lost due to genetic mutation, infectious
      disease, chemical ototoxicity, noise and other factors, causing permanent
      sensorineural deafness. Regeneration of hair cells is a basic pre-requisite for
      recovery of hearing in deaf animals. The inner ear stem cells in the organ of
      Corti and vestibular utricle are the most ideal precursors for regeneration of
      inner ear hair cells. This review highlights some recent findings concerning the
      proliferation and differentiation of inner ear stem cells. The differentiation of
      inner ear stem cells into hair cells involves a series of signaling pathways and
      regulatory factors. This paper offers a comprehensive analysis of the related
      studies. 

PMID- 24680895
TI  - Functional roles of Lgr4 and Lgr5 in embryonic gut, kidney and skin development
      in mice.
AB  - Lgr4 and Lgr5 are known markers of adult and embryonic tissue stem cells in
      various organs. However, whether Lgr4 and Lgr5 are important for embryonic
      development remains unclear. To study their functions during intestinal crypt,
      skin and kidney development we now generated mice lacking either Lgr4 (Lgr4KO),
      Lgr5 (Lgr5KO) or both receptors (Lgr4/5dKO). E16.5 Lgr4KO mice displayed complete
      loss of Lgr5+/Olfm4+intestinal stem cells, compromised Wnt signaling and impaired
      proliferation and differentiation of gut epithelium. Similarly, E16.5 Lgr4KO mice
      showed reduced basal cell proliferation and hair follicle numbers in the
      developing skin, as well as dilated kidney tubules and ectatic Bowman's spaces.
      Although Lgr4KO and Lgr5KO mice both died perinatally, Lgr5 deletion did not
      compromise embryonic development of gut, kidney or skin. Concomitant deletion of
      Lgr4 and Lgr5 did not prevent perinatal lethality, in contrast to a previous
      report that suggested rescue of Lgr5 KO perinatal lethality by a hypomorphic Lgr4
      mutant. While the double deletion did not further promote the phenotypes observed
      in Lgr4KO intestines, impaired kidney cell proliferation, reduced epidermal
      thickness, loss of Lgr5+follicular epithelium and impaired hair follicle
      development were only observed in Lgr4/5dKO mice. This supports complementary
      functions of both receptors. Our findings clearly establish the importance of
      Lgr4 and Lgr5 during embryonic gut, skin and kidney development, with a dominant
      role of Lgr4. 

PMID- 24680896
TI  - Direct transcriptional regulation by nuclear microRNAs.
AB  - The function of microRNAs is well characterized in the cytoplasm, where they
      direct an Argonaute-containing complex to target and repress mRNAs. More
      recently, regulatory roles for microRNAs and Argonaute have also been reported in
      the nucleus where microRNAs guide Argonaute to target gene promoters and directly
      regulate transcription in either a positive or a negative manner. Deep sequencing
      has revealed a high abundance of endogenous microRNAs within the nucleus, and in
      silico target prediction suggests thousands of potential microRNA:promoter
      interaction sites. The predicted high frequency of miRNA:promoter interactions is
      supported by chromatin immunoprecipitation, indicating the microRNA-dependent
      recruitment of Argonaute to thousands of transcriptional start sites and the
      subsequent regulation of RNA polymerase-II occupancy and chromatin modifiers. In
      this review we discuss the evidence for, and mechanisms associated with, direct
      transcriptional regulation by microRNAs which may represent a significant and
      largely unexplored aspect of microRNA function. This article is part of a
      Directed Issue entitled: The non-coding RNA revolution. 

PMID- 24680899
TI  - Lycium ruthenicum polysaccharide attenuates inflammation through inhibiting
      TLR4/NF-kappaB signaling pathway.
AB  - Polysaccharide has been reported to possess diverse biological activities,
      however, the inflammatory activity of polysaccharide isolated from Lycium
      ruthenicum remains unknown so far. In the present study, we investigated the
      effects of L. ruthenicum polysaccharide (LRGP3) on inflammatory reaction induced
      by lipopolysaccharide (LPS) in mouse macrophage RAW264.7 cells and some potential
      underlying mechanisms. Our results showed that LRGP3 treatment significantly
      inhibited the LPS-induced NO production and the mRNA expression of iNOS, as well
      as the level of Toll-like receptor 4 (TLR4). Furthermore, LRGP3 treatment
      prevented the IkappaBalpha degradation and reduced phospho-NF-kappaB p65 protein
      expression in LPS-stimulated RAW264.7 cells. Meanwhile, the levels of pro
      inflammatory cytokines, such as interleukin (IL)-alpha, IL-6, tumor necrosis
      factor (TNF)-alpha were suppressed by LRGP3 in LPS-stimulated RAW264.7 cells.
      Taken together, our results suggested that LRGP3 attenuated LPS-induced
      inflammation via inhibiting TLR4/NF-kappaB signaling pathway. 

PMID- 24680898
TI  - Association between morphometric variables and nocturnal desaturation in sickle
      cell anemia.
AB  - OBJECTIVE: to evaluate associations between morphometric variables, cervical
      circumference (CC), and abdominal circumference (AC) with the presence of
      nocturnal desaturation in children and adolescents with sickle-cell anemia.
      METHODS: all patients were submitted to baseline polysomnography, oral cavity
      measurements (maxillary intermolar distance, mandibular intermolar distance, and
      overjet), and CC and AC measurements. RESULTS: a total of 85 patients were
      evaluated. A positive correlation was observed between the height/age Z-score and
      CC measurement (r = 0.233, p = 0.031). The presence of nocturnal desaturation was
      associated with CC (59.2+/- 9.3 vs. 67.5 +/- 10.7, p = 0.006) and AC measurements
      (27.0 +/- 2.0 vs. 29.0+/- 2.1, p = 0.028). There was a negative correlation
      between desaturation and maxillary intermolar distance (r = -0.365, p = 0.001)
      and mandibular intermolar distance (r = -0.233, p = 0.037). CONCLUSIONS: the
      morphometric variables of CC and AC may contribute to raise suspicion of
      nocturnal desaturation in children and adolescents with sickle-cell anemia.

PMID- 24680900
TI  - Influence of temperature, mono- and divalent cations on dilute solution
      properties of sage seed gum.
AB  - The functional properties of food hydrocolloids are remarkably affected by the
      quality of solvent/cosolutes and temperature in a food system. In this paper,
      dilute solution properties of sage seed gum (SSG) as a function of salt type
      (NaCl, KCl, MgCl2 and CaCl2), salt concentration (10, 50, 100 and 200mM) and
      temperature (25, 45 and 65 degrees C) were investigated. Among various models,
      Higiro model showed a higher performance to determine intrinsic viscosity of SSG
      at all temperatures and cosolutes. From 25 to 65 degrees C for every 20 degrees C
      rise in temperature, intrinsic viscosity decreased about 18.99 and 63.86%,
      respectively. The divalent cations had more reduction effect on intrinsic
      viscosity than monovalet cations. More flexibility of SSG in monovalent salts
      solutions compared with divalent ones was observed. A high value for activation
      energy (2.53*10(7)J/kgmol) and chain flexibility (3046.45) of SSG was obtained,
      which was higher than many hydrocolloids. The shape factor of SSG macromolecules
      at 25-65 degrees C was an oblate or prolate and for all used cosolutes, the shape
      was roughly found to be ellipsoidal. 

PMID- 24680901
TI  - Comparative studies on the removal of heavy metals ions onto cross linked
      chitosan-g-acrylonitrile copolymer.
AB  - The graft copolymerization of acrylonitrile onto cross linked chitosan was
      carried out using ceric ammonium nitrate as an initiator. The prepared cross
      linked chitosan-g-acrylonitrile copolymer was characterized using FT-IR and XRD
      studies. The adsorption behavior of chromium(VI), copper(II) and nickel(II) ions
      from aqueous solution onto cross linked chitosan graft acrylonitrile copolymer
      was investigated through batch method. The efficiency of the adsorbent was
      identified from the varying the contact time, adsorbent dose and pH. The results
      evident that the adsorption of metal ions increases with the increase of shaking
      time and metal ion concentration. An optimum pH was found to be 5.0 for both
      Cr(VI) and Cu(II), whereas the optimum pH is 5.5 for the adsorption of Ni(II)
      onto cross linked chitosan-g-acrylonitrile copolymer. The Langmuir and Freundlich
      adsorption models were applied to describe the isotherms and isotherm constants.
      Adsorption isothermal data could be well interpreted by the Freundlich model. The
      kinetic experimental data properly correlated with the second-order kinetic
      model. From the above results it was concluded that the cross linked chitosan
      graft acrylonitrile copolymer was found to be the efficient adsorbent for
      removing the heavy metals under optimum conditions. 

PMID- 24680897
TI  - Regulation of mammary epithelial cell homeostasis by lncRNAs.
AB  - The epithelial cells of the mammary gland develop primarily after birth and
      undergo surges of hormonally regulated proliferation, differentiation, and
      apoptosis during both puberty and pregnancy. Thus, the mammary gland is a useful
      model to study fundamental processes of development and adult tissue homeostasis,
      such as stem and progenitor cell regulation, cell fate commitment, and
      differentiation. Long noncoding RNAs (lncRNAs) are emerging as prominent
      regulators of these essential processes, as their extraordinary versatility
      allows them to modulate gene expression via diverse mechanisms at both
      transcriptional and post-transcriptional levels. Not surprisingly, lncRNAs are
      also aberrantly expressed in cancer and promote tumorigenesis by disrupting vital
      cellular functions, such as cell cycle, survival, and migration. In this review,
      we first broadly summarize the functions of lncRNAs in mammalian development and
      cancer. Then we focus on what is currently known about the role of lncRNAs in
      mammary gland development and breast cancer. This article is part of a Directed
      Issue entitled: The Non-coding RNA Revolution. 

PMID- 24680902
TI  - Evaluation of antibacterial activity of N-phosphonium chitosan as a novel
      polymeric antibacterial agent.
AB  - N-phosphonium chitosans (NPCSs) with different degrees of substitution (3%, 13%
      and 21%) were synthesized and evaluated as novel polymeric antibacterial agents.
      Their antibacterial activities compared with hydroxypropyltrimethyl ammonium
      chloride chitosan (HACC), parent chitosan and (5-carboxypentyl)
      triphenylphosphonium bromide (CTPB) were tested against Escherichia coli and two
      strains of drug-resistance Staphylococcus aureus by minimal inhibitory
      concentration (MIC), minimum bactericidal concentration (MBC) and biofilm
      prevention assays. The results show that the NPCS with 3% or 13% substitution has
      lower MIC and MBC values and stronger ability to inhibit biofilm formation of all
      the three bacteria than HACC, chitosan and CTPB. In addition, the antibacterial
      activity of NPCSs increases with their substitution decreasing from 21% to 3%.
      Overall, the antibacterial activity of NPCS with 3% or 13% substitution is better
      than that of NPCS with 21% substitution, HACC with 22% substitution, chitosan and
      CTPB. It can be considered that NPCS with appropriate degree of substitution has
      favorable antibacterial activity and is a potential polymeric antibacterial
      agent. 

PMID- 24680903
TI  - The cough suppressive activity of sulfated glucuronoxylan from Fagus sylvatica L.
AB  - Hemicellulose polysaccharides represent a large group of natural renewable
      polymers, however, their application potency is still low. In our study a
      hardwood 4-O-methylglucuronoxylan was isolated by alkali peroxide extraction of
      Fagus sylvatica sawdust and modified into sulfated water soluble derivative
      (MGXS). Highly sulfated MGXS was characterized by HPLC, FTIR and NMR
      spectroscopies, and tested in vivo on chemically induced cough reflex and smooth
      muscles reactivity. Farmacological tests revealed an interesting antitussive
      activity of MGXS. Comparative tests with drug commonly used in a clinical
      practice revealed that antitussive activity of MGXS was lower than that of opioid
      receptor agonist codeine, the strongest antitussive drug. Furthermore, the
      specific reactivity of airways smooth muscle was not significantly affected by
      MGXS, indicating thus that the polymer is not involved in the bronchodilation
      process. 

PMID- 24680904
TI  - Characterization and antioxidative activities of polysaccharide in Chinese
      angelica and its processed products.
AB  - Five polysaccharides from unprocessed Chinese angelica (UCAP), parched one with
      alcohol (ACAP), soil (SCAP), sesame oil (OCAP) and parched into charred (CCAP)
      were extracted and purified. Their structures were identified by Fourier
      transform-infrared spectroscopy (FT-IR), compositions were analyzed by gas
      chromatography-mass spectrometry (GC-MS) and antioxidative activities were
      compared by determining MDA contents and SOD activities of liver tissue in mice
      damaged with CCl4 after gavage. The results showed that the FT-IR spectra of CCAP
      and OCAP displayed lower transmittance at around 1050cm(-1) in comparison with
      that of UCAP. Five polysaccharides were all composed of rhamnose, arabinose,
      mannose, glucose and galactose. In CCAP, ACAP, OCAP and SCAP, the proportions of
      arabinose were significantly increased in comparison with that of UCAP. The SOD
      activities in CCAP and SCAP groups were significantly enhanced, and MDA contents
      in CCAP, OCAP and SCAP groups were significantly decreased as compared with UCAP
      group. This indicated that processing could change the structure, composition and
      enhance antioxidative activity of polysaccharide in Chinese angelica, and CCAP
      possessed the strongest antioxidative activity. 

PMID- 24680905
TI  - Regional differences of microglial accumulation within 72 hours of hypoxia
      ischemia and the effect of acetylcholine receptor agonist on brain damage and
      microglial activation in newborn rats.
AB  - OBJECTIVE: We examined regional specificity of microglial activation in the
      developing rat brain for 72 hours after hypoxia-ischemia (HI) and the effect of
      acetylcholine receptor (AChR) agonist on microglial activation. STUDY DESIGN:
      Seven-day-old Wistar rats were divided into two groups: one receiving a single
      dose of AChR agonist just before hypoxia (carbachol; 0.1mg/kg) to investigate the
      reducing effect on brain damage with decreasing activation of microglia and the
      other group receiving saline as a control. Rats were subjected to left carotid
      artery ligation followed by 8% hypoxia. Brains were analyzed
      immunohistochemically at 24, 48, and 72 hours after HI. TNFalpha production was
      measured at respective times after HI. RESULTS: Activation of microglia on the
      hippocampus of the control group was strong for the first 48 hours and then
      weakened. In contrast, activation of microglia on white matter and the cortex was
      weak at 24 hours and then became stronger. A single dose of carbachol
      significantly reduced brain damage with a marked reduction of microglial
      activation on the hippocampus, whereas it was less effective regarding microglial
      activation on white matter and the cortex. TNFalpha production was low in both
      groups. CONCLUSION: Regional specificity was observed for both microglial
      activation and susceptibility to carbachol for the first 72 hours after HI. Our
      data suggested that timely intervention along with region-specific microglial
      activation, apart from TNFalpha production, may be critical for the prevention of
      further brain damage after HI in the newborn.

PMID- 24680906
TI  - The effects of superoxide dismutase mimetic MnTMPyP on the altered blood-brain
      barrier integrity in experimental preeclampsia with or without seizures in rats.
AB  - We investigated the effects of a cell-permeable superoxide dismutase mimetic,
      manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) on blood-brain
      barrier (BBB) integrity following pentylenetetrazole (PTZ)-induced seizures in
      experimental preeclampsia symptoms induced by N(omega)-nitro-l-arginine methyl
      ester (l-NAME) in pregnant rats. To show the functional and morphological
      alterations in BBB integrity, quantitative analysis of sodium fluorescein (NaFlu)
      extravasation, immunohistochemistry and electron microscopic assessment of
      horseradish peroxidase (HRP) permeability were performed. Varying degrees of
      proteinuria were seen and arterial blood pressure increased in l-NAME-treated
      pregnant rats (p<0.01). MnTMPyP pretreatment and convulsive PTZ challenge
      significantly decreased the immunoreactivity of occludin in hippocampal
      capillaries in l-NAME-treated pregnant rats (p<0.01). BBB permeability to NaFlu
      significantly increased in pregnant rats treated with l-NAME plus PTZ (p<0.01),
      but MnTMPyP pretreatment did not significantly decrease NaFlu penetration into
      the brain parenchyma in these animals. Ultrastructurally, frequent vesicles
      containing HRP reaction products were observed in the capillary endothelial cells
      in the cerebral cortex and hippocampus of pregnant rats treated with l-NAME and l
      NAME plus PTZ with the abundance being more in the latter group. MnTMPyP
      pretreatment caused a marked reduction in the frequency of HRP reaction product
      containing vesicles in both experimental settings. In conclusion, the results of
      the present study provide evidence that MnTMPyP plays an important role in
      limiting the enhanced vesicle-mediated transcellular transport in BBB endothelium
      in a rat model of preeclampsia and the differences in the way of transports of
      NaFlu and HRP might be responsible for the different effects of MnTMPyP on the
      BBB permeability to these two tracers.

PMID- 24680907
TI  - An electrophysiological study of haptic roughness: effects of levels of texture
      and stimulus uncertainty in the P300.
AB  - This study investigated the neural mechanisms implicated in tactile perception
      using a discrimination task. We also investigated the influence of the type of
      presentation on the subject's uncertainty. The stimuli varied across four levels
      of roughness and were presented using a pure/mixed block design. We used an
      oddball paradigm with three target stimuli varying in the level of roughness, and
      a smooth surface as the non-target. Stimuli were presented using a specific
      purpose device. We analyzed the modulation of the P300 amplitude elicited by
      targets and non-targets in both presentation conditions. The results showed that
      the P300 waveform was modulated by roughness, as well as by the order of stimuli
      presentation. The P300 amplitude was more sensitive to roughness when stimuli
      were presented in mixed blocks (higher uncertainty). The results are discussed in
      the context of the attention resources allocation theory applied to tactile
      modality.

PMID- 24680909
TI  - The immunomodulatory effects of pegylated liposomal doxorubicin are amplified in
      BRCA1--deficient ovarian tumors and can be exploited to improve treatment
      response in a mouse model.
AB  - OBJECTIVE: Women with BRCA-associated ovarian cancer demonstrate excellent
      responses to Pegylated Liposomal Doxorubicin (PLD). PLD has also been shown to
      enhance T cell recognition of tumor cells. Here we characterize immunophenotypic
      changes associated with BRCA1 dysfunction in ovarian cancer cells, and evaluate
      the T cell contribution to the therapeutic efficacy of PLD in a BRCA1- ovarian
      cancer model to determine whether enhanced anti-tumor immunity contributes to the
      improved response to PLD in BRCA1- ovarian cancers. METHODS: The immunophenotype
      of BRCA1- and wild-type (WT) ovarian cancer cells and their response to PLD were
      compared in vitro using flow cytometry. T cell recruitment to BRCA1- tumors was
      evaluated with flow cytometry and immunohistochemistry. The contribution of T
      cell populations to the therapeutic effect of PLD in a BRCA1- model was evaluated
      using immunodepleting antibodies with PLD in vivo. RESULTS: The cytotoxic
      response to PLD was similar in BRCA1- and WT cells in vitro. BRCA1- inactivation
      resulted in higher expression of Fas and MHC-I at baseline and after PLD
      exposure. PLD prolonged the survival of BRCA1- tumor bearing mice and increased
      intratumoral T cell recruitment. CD4+ depletion combined with PLD significantly
      prolonged overall survival (p=0.0204) in BRCA1- tumor-bearing mice. CONCLUSION:
      Differences in the immunophenotype of BRCA1- and WT cells are amplified by PLD
      exposure. The enhanced immunomodulatory effects of PLD in BRCA1- tumors may be
      exploited therapeutically by eliminating suppressive CD4+ T cells. Our results
      support further study of combination therapy using PLD and immune agents,
      particularly in women with BRCA gene mutations.

PMID- 24680908
TI  - Semi-automatic quantification of neurite fasciculation in high-density neurite
      images by the neurite directional distribution analysis (NDDA).
AB  - BACKGROUND: Bundling of neurite extensions occur during nerve development and
      regeneration. Understanding the factors that drive neurite bundling is important
      for designing biomaterials for nerve regeneration toward the innervation target
      and preventing nociceptive collateral sprouting. High-density neuron cultures
      including dorsal root ganglia explants are employed for in vitro screening of
      biomaterials designed to control directional outgrowth. Although some semi
      automated image processing methods exist for quantification of neurite outgrowth,
      methods to quantify axonal fasciculation in terms of direction of neurite
      outgrowth are lacking. NEW METHOD: This work presents a semi-automated program to
      analyze micrographs of high-density neurites; the program aims to quantify axonal
      fasciculation by determining the orientational distribution function of the
      tangent vectors of the neurites and calculating its Fourier series coefficients
      ('c' values). RESULTS: We found that neurite directional distribution analysis
      (NDDA) of fasciculated neurites yielded 'c' values of >=~0.25 whereas branched
      outgrowth led to statistically significant lesser values of <~0.2. The 'c' values
      correlated directly to the width of neurite bundles and indirectly to the number
      of branching points. COMPARISON WITH EXISTING METHODS: Information about the
      directional distribution of outgrowth is lost in simple counting methods or
      achieved laboriously through manual analysis. The NDDA supplements previous
      quantitative analyses of axonal bundling using a vector-based approach that
      captures new information about the directionality of outgrowth. CONCLUSION: The
      NDDA is a valuable addition to open source image processing tools available to
      biomedical researchers offering a robust, precise approach to quantification of
      imaged features important in tissue development, disease, and repair.

PMID- 24680910
TI  - Comparision of efficacy of two experimental bovine leptospira vaccines under
      laboratory and field.
AB  - Two different inactivated vaccines for bovine leptospirosis were prepared with
      five different Leptospira serovars namely australis, ballum, hardjo, hebdomadis
      and pomona and adjuvanted with Montanide ISA 206 (Vaccine-I) or adjuvanted with
      Aluminium hydroxide gel (Vaccine-II) to evaluate the efficacy of the vaccines.
      The immunogenicity of the vaccines was studied in rabbits under experimental
      condition and in cattle under field condition for a period of 180 days. Antibody
      response against five different leptospira serovars ranged from 6.84 log2 to 9.64
      log2 (GM-MAT titres) in rabbits at 180 days after vaccination with vaccine I,
      whereas in vaccine II, the titre value ranged from 5.64 log2 to 7.44 log2. In the
      case of cattle under field condition, vaccine I showed GM-MAT titres of 6.84 log2
      to 7.69 log2 against five different serovars at 150 days following vaccination.
      Such titres were maintained following vaccination with vaccine II for 120 days
      only. It is concluded that vaccine I is a better vaccine than vaccine II. However
      both the vaccines showed high immune response of 5.64 log2 at six months of
      immunization. Vaccination did not cause any adverse reaction in the vaccinated
      cattle.

PMID- 24680911
TI  - Expression profiling of pattern recognition receptors and selected cytokines in
      miniature dachshunds with inflammatory colorectal polyps.
AB  - Inflammatory colorectal polyps (ICRPs) are commonly seen in miniature dachshund
      (MD) dogs; typically, multiple polyps form with severe neutrophil infiltration.
      ICRP is thought to be a novel form of inflammatory bowel disease (IBD), but its
      etiology has not been investigated. The innate immune system is implicated in the
      pathogenesis of both human and canine IBD. Therefore, the aim of the current
      study was to evaluate the messenger RNA (mRNA) expression profiles of pattern
      recognition receptors (PRRs) and cytokines in ICRPs. Polyp tissues were collected
      by colonoscopic biopsies from 24 MDs with ICRPs. Non-polypoid colonic mucosa was
      collected from all MDs with ICRPs and 21 clinically healthy beagles (as the
      controls). The expression levels of the mRNAs encoding toll-like receptors (TLRs)
      1-10; nucleotide-binding oligomerization domain (NOD)-like receptors NOD1 and
      NOD2; and cytokines IL-1beta, IL-6, IL-8/CXCL8, and TNF-alpha were evaluated by
      quantitative real-time RT-PCR. Three of the 10 well-known candidate reference
      genes were selected as housekeeper genes based on analyses from the GeNorm,
      NormFinder, and BestKeeper programs. Levels of TLR1, TLR2, TLR4, TLR6, TLR7,
      TLR8, TLR9, TLR10, NOD2, and all cytokines were significantly upregulated in the
      polyps relative to those in the controls. There was significant decrease in the
      expression levels of TLR3 and NOD1 in the polyp tissues compared to the non
      polypoid colonic mucosa obtained from MDs with ICRPs. All upregulated PRR mRNAs
      were positively correlated with all proinflammatory cytokine mRNAs. This study
      demonstrated the dysregulation of PRRs and proinflammatory cytokines in ICRPs of
      MDs, which may play an important role in the pathogenesis of this disease.

PMID- 24680912
TI  - The income body weight gradients in the developing economy of China.
AB  - Existing theories predict the income gradient of individual body weight to change
      sign from positive to negative in process of economic development. However, there
      are only few empirical studies which test this hypothesis. This paper adds to the
      literature on that topic by investigating the case of China. Using individual and
      community data from 1991 to 2009 waves of the China Health and Nutrition Survey
      regression analyses suggest that after controlling for important confounding
      factors (1) higher income is positively related to future growth of individuals'
      BMI in less developed areas (i.e. BMI growth is 0.7-1.5 percentage points higher
      when comparing the richest with the poorest individuals), but negatively related
      to BMI growth in more developed areas (i.e. BMI growth is 0.8-1.6 percentage
      points lower for the richest individuals), and (2) that concentrations of
      overweight are "trickling down" to lower income ranks as regions become more
      developed. Moreover, the reversal of the income gradient appears to happen at
      earlier stages of development for females. 

PMID- 24680913
TI  - Plasma and synovial fluid sclerostin are inversely associated with radiographic
      severity of knee osteoarthritis.
AB  - OBJECTIVE: The purpose of this study was to analyze sclerostin in plasma and
      synovial fluid of knee osteoarthritis (OA) patients and to investigate the
      association between sclerostin levels and radiographic severity. DESIGN AND
      METHODS: A total of 190 subjects (95 knee OA patients and 95 healthy controls)
      were recruited in the present study. Sclerostin levels in plasma and synovial
      fluid were assessed using an enzyme-linked immunosorbent assay. OA grading was
      performed using the Kellgren-Lawrence classification. RESULTS: Plasma sclerostin
      levels were significantly lower in OA patients than in healthy controls
      (P=0.004). Additionally, sclerostin levels in plasma were significantly higher
      with respect to paired synovial fluid (P<0.001). Moreover, sclerostin levels in
      plasma and synovial fluid demonstrated a significant inverse correlation with the
      radiographic severity of knee OA (r=-0.464, P<0.001 and r=-0.592, P<0.001,
      respectively). Subsequent analysis revealed that there was a positive correlation
      between plasma and synovial sclerostin levels (r=0.657, P<0.001). CONCLUSIONS:
      Sclerostin was significantly lower in OA plasma samples when compared with
      healthy controls. Plasma and synovial fluid sclerostin levels were inversely
      associated with the radiographic severity of knee OA. Therefore, sclerostin may
      be utilized as a biochemical marker for reflecting disease severity in primary
      knee OA.

PMID- 24680914
TI  - Phylogenetic relationships within the snapping shrimp genus Synalpheus (Decapoda:
      Alpheidae).
AB  - The snapping shrimp genus Synalpheus (Alpheidae) is one of the most speciose
      decapod genera, with over 160 described species worldwide. Most species live in
      symbiotic relationships with other marine organisms, such as sponges, corals and
      crinoids, and some sponge-dwelling species have a highly organized, social
      structure. The present study is the first worldwide molecular phylogenetic
      analysis of Synalpheus, based on >2,200 bp of sequence data from two
      mitochondrial (COI and 16S) and two nuclear (PEPCK and 18S) loci. Our molecular
      data show strong support for monophyly of three out of six traditionally
      recognized morphology-based species groups: the S. brevicarpus, S. comatularum
      and S. gambarelloides groups. The remaining three species groups (S. paulsoni, S.
      neomeris and S. coutierei groups) are non-monophyletic in their current
      composition and will need to be either abandoned or taxonomically redefined. We
      also identified potential cryptic species of Synalpheus in our dataset, using
      intraspecific and interspecific sequence variation in COI from the taxonomically
      well-studied S. gambarelloides group to establish a genetic divergence threshold.
      We then used both genetic divergence and tree-based criteria (reciprocal
      monophyly) to identify potential cryptic species in the remaining taxa of the
      genus. Our results suggest the presence of multiple cryptic lineages in
      Synalpheus, underlining the need for more integrative taxonomic studies-including
      morphological, ecological, molecular, and color pattern data-in this biologically
      interesting genus.

PMID- 24680915
TI  - The comprehensive phylogeny of the superfamily Elateroidea (Coleoptera:
      Elateriformia).
AB  - Elateriformia consists of Dascilloidea, Buprestoidea (jewel beetles), Byrrhoidea
      and Elateroidea (click beetles, fireflies and relatives). Numerous elateroid
      lineages contain taxa with modified metamorphosis resulting in sexual maturity
      while retaining larval characters. Additionally, they evolved unique defensive
      strategies including clicking mechanism, aposematic coloration and
      bioluminescence. To investigate the phylogenetic position of Elateroidea within
      Coleoptera, we merged 1048 newly produced 18S rRNA, 28S rRNA, rrnL mtDNA, and
      cox1 mtDNA sequences for ~300 elateriform taxa with data from GenBank. The 975
      taxa dataset aligned in BlastAlign was analyzed under maximum likelihood
      criterion. The results agreed in most aspects with the current morphology-based
      classification and results of molecular studies. Elateriformia were monophyletic
      and Elateroidea were sister to Byrrhoidea. Further, we analyzed all-data (513
      elateriform taxa) and pruned matrix (417 elateriform taxa, all fragments present)
      using parsimony and maximum likelihood methods to reveal the phylogenetic
      relationships among elateroid lineages and examine the evolution of soft
      bodiedness, neoteny and bioluminescence. We confirmed the monophyly of
      Elateroidea sensu lato and most of the families, with Telegeusidae inferred in
      most trees within paraphyletic Omethidae. The clade
      Artematopodidae+Telegeusidae+Omethidae was a sister to remaining elateroids. All
      topologies reject the relationships of hard-bodied Elateridae, Eucnemidae,
      Throscidae and Cerophytidae, formerly supposed to be a monophylum. Eucnemidae and
      Throscidae formed independent lineages and the position of Cerophytidae was
      variable - either a sister to Throscidae, or an independent lineage. The
      Lampyridae+Cantharidae clade was in most trees sister to
      Phengodidae+Rhagophthalmidae+Omalisidae+Elateridae. Molecular phylogeny of
      Elateroidea confirmed the multiple origins of soft-bodied, neotenic and light
      emiting lineages. On the basis of our molecular phylogeny, we place former
      Telegeusidae as a subfamily in Omethidae. 

PMID- 24680916
TI  - Transantarctic disjunctions in Schistochilaceae (Marchantiophyta) explained by
      early extinction events, post-Gondwanan radiations and palaeoclimatic changes.
AB  - The liverworts are the first diverging land plant group with origins in the
      Ordovician. The family Schistochilaceae exhibits diverse morphology and widely
      disjunct geographic ranges within the Southern Hemisphere. The family has been
      presented as a classic example of Gondwanan biogeographic distribution, with
      extant species ranges resulting from vicariance events. In this study, we present
      results that elucidate the origin and diversification of Schistochilaceae. We
      conducted a comprehensive time-calibrated, molecular-based phylogenetic analysis
      and different approaches for ancestral range inference of the family.
      Schistochilaceae is inferred to have originated in the Late Cretaceous, in an
      ancestral area including southern South America, West Antarctica and New Zealand.
      Despite a family origin at c. 100Ma, most of the diversification of
      Schistochilaceae occurred in New Zealand after the 80Ma opening of the Tasman Sea
      that isolated New Zealand from the rest of Gondwana. Most dispersals were
      transoceanic. The northward migration of the Schistochilaceae is probably linked
      with the spread of temperate vascular plant forest ecosystems that have Late
      Cretaceous southern origins and have maintained suitable environments for the
      family throughout the Cenozoic. The distribution and biogeographic history of the
      family is very similar to that of Nothofagaceae. 

PMID- 24680917
TI  - Molecular markers from different genomic compartments reveal cryptic diversity
      within glaucophyte species.
AB  - Glaucophytes are the least studied of the three major Archaeplastida (Plantae
      sensu lato) lineages. It has been largely recognized that comprehensive
      investigations of glaucophyte genetic and species diversity will shed light on
      the early evolution of photosynthetic eukaryotes. Here we used molecular
      phylogenetics and genetic distance estimations of diverse molecular markers to
      explore strain and species diversity within the glaucophyte genera Cyanophora and
      Glaucocystis. Single gene and concatenated maximum likelihood analyses of markers
      from three different genetic compartments consistently recovered similar
      intrageneric genetic groups. Distance analyses of plastid (psbA and rbcL) and
      mitochondrial (cob and cox1) genes, and the nuclear internal transcribed spacer
      (ITS) region, revealed substantial genetic divergence between some Cyanophora
      paradoxa and Glaucocystis nostochinearum strains. The genetic distances estimated
      between some glaucophyte strains currently considered the same species are
      similar or greater than divergence values calculated between different species in
      other unicellular algae, such as certain green algae and diatoms. The analyzed
      molecular markers are prospective candidates for future studies of species
      diversity in glaucophytes. Overall, our results unveil previously unrecognized
      cryptic diversity within Cyanophora and Glaucocystis species. 

PMID- 24680918
TI  - Tasks and communication as an avenue to enhance parenting of children birth-5
      years: an integrative review.
AB  - Every day, normative functions of parenting and their significance are under
      investigated. An integrative review of tasks and communication involved in
      parenting young children informed by Horowitz (1995) and Blumer (1969) was
      conducted.Research articles consistent with inclusion criteria were published
      from 1995 to 2013 and focused on parenting tasks and communication. Themes
      consistent with Horowitz and Blumer were identified. Nurses are reminded about
      the significance of attending to the everyday, normative work of parenting young
      children, the potential meaning derived from this work, and the importance of
      assessing parental development as well as the importance of continuing research
      in this area. 

PMID- 24680919
TI  - Acculturation, risk behaviors and physical dating violence victimization among
      Cuban-American adolescents.
AB  - The purpose of this study is to describe the relationships among acculturation,
      risk behaviors, and reported physical dating violence among Cuban-American ninth
      grade adolescents. Participants (N=82) completed a questionnaire that assessed
      their level of acculturation to the U.S. (Americanism), their maintenance of the
      Hispanic culture (Hispanicism), binge drinking, drug use, sexual intercourse,
      condom use and physical dating violence victimization. Multiple logistic
      regression was conducted. Hispanicism was associated with a decrease in odds of
      reporting physical dating violence victimization. Drug use and not using a condom
      were associated with an increase in odds of reporting physical dating violence
      victimization. 

PMID- 24680920
TI  - Stress relaxation behaviors of articular cartilages in porcine temporomandibular
      joint.
AB  - In this study, we tested the compressive stress relaxation behaviors of the
      mandibular condylar and temporal cartilages in the porcine temporomandibular
      joint (TMJ). The aim was to determine the quantitative and qualitative
      similarities and differences of compressive stress relaxation behaviors between
      the two cartilages. Ten porcine TMJs were used; the articular surface was divided
      into 5 regions: anterior, central, posterior, lateral and medial. Compressive
      relaxation test was carried out at a strain level of 5% in each region of the two
      cartilages. The stress relaxation was monitored over a period of 5min. In all the
      regions of the two cartilages, the time-dependent stress relaxation curves showed
      a marked drop in stress within the initial 10s, which can be fitted by a standard
      linear viscoelastic model. The instantaneous moduli in the temporal cartilage
      were dominantly larger than those in the condylar cartilage, while the condylar
      cartilage had slightly larger relaxation moduli than the temporal cartilage
      except for the medial region. The both cartilages showed the regional differences
      in the compressive stress relaxation behavior, and in the temporal cartilage the
      lateral and medial regions revealed the largest values for the instantaneous and
      relaxation moduli. The present results demonstrate that the viscoelastic
      properties of compressive stress relaxation in both cartilages are region
      specific, which might have an important implication for stress distribution and
      transmission along with the TMJ disc. 

PMID- 24680921
TI  - Article by Singla et al.

PMID- 24680922
TI  - A novel integrated strategy for detection of human bocavirus based on a
      heminested PCR assay combined with boiling lysis method of samples in human
      specimens.
AB  - Human bocavirus (HBoV) has been shown to be associated with acute respiratory
      tract infection in children. The aim of the work was to develop a novel
      integrated strategy for human bocavirus detection: heminested PCR assay combined
      with boiling lysis method of samples. The detection limit of the heminested PCR
      assay was 1.2 copies of a recombinant DNA plasmid, and no cross-reaction with
      other respiratory viruses or bacteria was observed. By using the integrated
      strategy, a total of 202 secretions of the lower respiratory tract of children
      with acute respiratory diseases were collected and tested. The samples were
      treated and lysed in boiling lysis buffer rather than extracting viral DNA from
      secretions, then these sample lysates could be templates and tested by heminested
      PCR assay, and the amplification of HBoV DNA was detected by using agarose gel
      electrophoresis. The results showed that, only 7 samples were found to be
      positive by conventional single-round PCR; importantly, the other new 41 samples
      were positive by heminested PCR assay. Additionally, the genomic viral DNA was
      extracted from all positive and some negative specimens, amplified, and
      sequenced. The results were perfectly consistent with those of the integrated
      strategy. Taken together, these results suggest that the novel integrated
      strategy (heminested PCR assay combined with boiling lysis method of samples) is
      a convenient, sensitive, cost-effective and reliable detective method for HBoV
      detection and will have broad application prospects in clinical diagnosis. 

PMID- 24680923
TI  - The volatile anesthetic isoflurane differentially suppresses the induction of
      erythropoietin synthesis elicited by acute anemia and systemic hypoxemia in mice
      in an hypoxia-inducible factor-2-dependent manner.
AB  - Erythropoietin (EPO) is a glycoprotein hormone essential for the regulation of
      erythroid homeostasis. Although EPO production is prominent in the kidney and
      liver, its production in the central nervous system has also been detected.
      Tissue hypoxia due to systemic or local hypoxemia and acute anemia due to blood
      loss occurs frequently during various clinical settings, leading to a high
      possibility of elevated plasma EPO levels. However, it is largely unknown whether
      volatile anesthetic agents affect EPO production elicited by acute hypoxia in
      vivo. Male C57BL/6N CrSlc mice were exposed to a hypoxic insult as a result of
      bleeding-related anemia or hypoxemia while they were under anesthetized using
      various concentrations of isoflurane. EPO protein concentrations were assessed by
      enzyme-linked immunosorbent assay and mRNA levels were measured by quantitative
      real-time reverse transcriptase-polymerase chain reaction. Plasma EPO
      concentration was induced as early as 3h following acute anemic and hypoxemic
      hypoxia and suppressed by clinically relevant doses of isoflurane in a dose
      dependent manner. Anemic hypoxia induced EPO mRNA and protein synthesis in the
      kidney. In the kidney, isoflurane inhibited EPO induction caused by anemia but
      not that caused by hypoxemia. On the other hand, in the brain hypoxemia-induced
      EPO production was suppressed by isoflurane. Finally, qRT-PCR studies demonstrate
      that isoflurane differentially inhibit HIF-1alpha and HIF-2alpha mRNA expression
      in brain and kidney, indicating the involvement of HIF-2 in the hypoxia-induced
      EPO expression and inhibition of the induction by isoflurane. 

PMID- 24680924
TI  - Esters of valerenic acid as potential prodrugs.
AB  - Valerenic acid (VA) is a beta2/3 subunit-specific modulator of gamma-aminobutyric
      acid (GABA) type A (GABAA) receptors inducing anxiolysis. Here we analyze if VA
      esters can serve as prodrugs and if different ester structures have different in
      vitro/in vivo effects. Modulation of GABAA receptors expressed in Xenopus oocytes
      was studied with 2-microelectrode-voltage-clamp. Anxiolytic effects of the VA
      esters were studied on male C57BL/6N mice by means of the elevated plus maze
      test; anticonvulsant properties were deduced from changes in seizure threshold
      upon pentylenetetrazole infusion. VA was detected in plasma confirming hydrolysis
      of the esters and release of VA in vivo. Esterification significantly reduced the
      positive allosteric modulation of GABAA (alpha1beta3gamma2S) receptors in vitro.
      in vivo, the studied VA-ester derivatives induced similar or even stronger
      anxiolytic and anticonvulsant action than VA. While methylation and propylation
      of VA resulted in faster onset of anxiolysis, the action of VA-ethylester was
      longer lasting, but occurred with a significant delay. The later finding is in
      line with the longer lasting anticonvulsant effects of this compound. The
      estimated VA plasma concentrations provided first insight into the release
      kinetics from different VA-esters. This might be an important step for its future
      clinical application as a potential non-sedative anxiolytic and anticonvulsant. 

PMID- 24680925
TI  - Active and peripheral anionic sites of acetylcholinesterase have differential
      modulation effects on cell proliferation, adhesion and neuritogenesis in the
      NG108-15 cell line.
AB  - The classical enzymatic role of acetylcholinesterase (AChE) is to terminate
      impulse transmission at cholinergic synapses through rapid hydrolysis of
      acetylcholine (ACh). Inactivation of this enzyme's catalytic site is the primary
      mechanism of acute toxicity of OP insecticides (e.g. parathion, chlorpyrifos).
      There is now sufficient evidence to suggest that AChE has a neurotrophic function
      that may be altered by organophosphate (OP) exposure, resulting in defects of
      neuronal growth and development, though the clarification of the mechanisms
      involved require further in vitro investigation. In the present study, the mouse
      neuroblastoma*rat glioma hybrid NG108-15 cell line was used to investigate the
      differential effects between inhibition of the catalytic site and peripheral
      anionic site (PAS) of acetylcholinesterase (AChE) on cell adhesion, proliferation
      and neuritogenesis, in the presence and absence of human red blood cell (hRBC)
      AChE (ED3.1.1.7). AChE active-site inhibitor paraoxon (PO; 0.1-1.0MUM), when
      added to NG108-15 cells grown on AChE-coated plates, had no effect on cell
      proliferation, but exerted a significant reduction in strongly adherent viable
      cells accompanied by mostly short process formations, with 18% of cells
      considered to be neuritogenic, similar to that observed on uncoated plates. In
      contrast, PO had no significant effect on cell adhesion and proliferation of
      NG108-15 cells on uncoated plates. The PAS-ligand thioflavin-T (Th-T; 0.5-25MUM),
      however, decreased cell adhesion and proliferation, on both uncoated and ACh-E
      coated plates, with less magnitude on AChE-coated plates. Taken together, these
      results suggest that strong cell adherence and neuritogenesis are sensitive to PO
      in this cell culture model, with no impact on proliferation, in the presence of
      membrane bound AChE-coating, while there is no sensitivity to PO on uncoated
      plates. On the other hand, binding of Th-T directly to the PAS affects both cell
      adherence and proliferation, with less magnitude in the presence of membrane
      bound AChE. The current study indicates that PO is deleterious in neural
      development during critical periods of strong cell adhesion and differentiation,
      interfering with AChE trophic function. 

PMID- 24680926
TI  - Metallothionein prevents intermittent hypoxia-induced cardiac endoplasmic
      reticulum stress and cell death likely via activation of Akt signaling pathway in
      mice.
AB  - Endoplasmic reticulum (ER) stress, an adaptive response normally, causes
      apoptotic cell death under pathological conditions. Cardiac ER stress and
      associated cell death involve in the inflammatory responses that often cause
      cardiac remodeling and dysfunction. Here we examined whether chronic intermittent
      hypoxia (IH) induces cardiac ER stress and associated cell death along with
      inflammatory response and if so, whether these effects can be affected by
      transgenic overexpression or deletion of metallothionein gene (MT-TG or MT-KO).
      IH exposures for 3 days to 4 weeks significantly increased cardiac ER stress and
      apoptosis, shown by the increased expression of GRP78, ATF6 and CHOP, the
      activation of caspase-12 and capase-3, and the decreased Bcl2/Bax expression
      ratio, predominantly in the 3rd week of IH exposures. These effects were
      significantly exacerbated in MT-KO mice, but completely prevented in MT-TG mice.
      In vitro mechanistic study with H9c2 cardiac and primary neonatal cardiomyocytes
      showed that MT protection from ER stress-induced apoptosis was mediated by up
      regulating Akt phosphorylation since inhibition of Akt phosphorylation abolished
      MT's protection MT from ER stress and apoptosis. These findings suggest that
      chronic IH is able to induce cardiac ER stress, cell death and inflammation can
      be prevented by MT, probably via up-regulation of Akt function. 

PMID- 24680927
TI  - Ziyuglycoside II induces cell cycle arrest and apoptosis through activation of
      ROS/JNK pathway in human breast cancer cells.
AB  - Ziyuglycoside II, a triterpenoid saponin compound extracted from Sanguisorba
      officinalis L., has been reported to have a wide range of clinical applications
      including anti-cancer effect. In this study, the anti-proliferative effect of
      ziyuglycoside II in two classic human breast cancer cell lines, MCF-7 and MDA-MB
      231, was extensively investigated. Our study indicated that ziyuglycoside II
      could effectively induce G2/M phase arrest and apoptosis in both cell lines. Cell
      cycle blocking was associated with the down-regulation of Cdc25C, Cdc2, cyclin A
      and cyclin B1 as well as the up-regulation of p21/WAF1, phospho-Cdc25C and
      phospho-Cdc2. Ziyuglycoside II treatment also induced reactive oxygen species
      (ROS) production and apoptosis by activating the extrinsic/Fas/FasL pathway as
      well as the intrinsic/mitochondrial pathway. More importantly, the c-Jun NH2
      terminal kinase (JNK), a downstream target of ROS, was found to be a critical
      mediator of ziyuglycoside II-induced cell apoptosis. Further knockdown of JNK by
      siRNA could inhibit ziyuglycoside II-mediated apoptosis with attenuating the up
      regulation of Bax and Fas/FasL as well as the down-regulation of Bcl-2. Taken
      together, the cell death of breast cancer cells in response to ziyuglycoside II
      was dependent upon cell cycle arrest and cell apoptosis via a ROS-dependent JNK
      activation pathway. Our findings may significantly contribute to the
      understanding of the anti-proliferative effect of ziyuglycoside II, in particular
      to breast carcinoma and provide novel insights into the potential application of
      such compound in breast cancer therapy. 

PMID- 24680928
TI  - Arsenic trioxide attenuates the invasion potential of human liver cancer cells
      through the demethylation-activated microRNA-491.
AB  - Hepatocellular carcinoma (HCC) represents the third leading cause of cancer
      related mortality worldwide. Current standard practices for treatment of HCC are
      less than satisfactory because of metastasis and recurrence. In addition to
      treating acute promyelocytic leukemia (APL), arsenic trioxide (As2O3) also
      suppresses other solid tumors, such as HCC. However, the effects of As2O3 on the
      migration/invasion potential of liver cancer cells and the molecular mechanisms
      underlying in remain unclear. Here we found that As2O3 attenuated the
      migration/invasion potential of HCC cell lines by blocking matrix
      metalloproteinases (MMPs) activities and inducing a mesenchymal to epithelial
      transition (MET). Indeed, As2O3 elevated the expression of microRNA-491 (miR-491)
      via demethylation. On one hand, as a target miRNA of MMP9, miR-491 decreased the
      MMP9 expression. On the other hand, miR-491 blocked the activation of nuclear
      factor kappaB (NF-kappaB), which transcriptionally inactivated MMP2 and induced a
      MET (as determined by the increased expression of E-cadherin and decreased
      expressions of snail, slug, and vimentin). Knockdown of miR-491 abolished the
      As2O3-induced MMPs inactivation, MET, and the migration/invasion potential of HCC
      cell lines. By understanding a novel mechanism how As2O3 inhibits the
      migration/invasion potential of liver cancer cells, our study may help to
      identify potential therapeutic targets for liver cancer. 

PMID- 24680929
TI  - Phenotypes and biomarkers of diabetic retinopathy.
AB  - Diabetic retinopathy (DR) remains a major cause of blindness as the prevalence of
      diabetes is expected to approximately double globally between 2000 and 2030. DR
      progresses over time at different rates in different individuals with only a
      limited number developing significant vision loss due to the two major vision
      threatening complications, clinically significant macular edema and proliferative
      retinopathy. Good metabolic control is important to prevent and delay
      progression, but whereas some patients escape vision loss even with poor control,
      others develop vision loss despite good metabolic control. Our research group has
      been able to identify three different DR phenotypes characterized by different
      dominant retinal alterations and different risks of progression to vision
      threatening complications. Microaneurysm turnover has been validated as a
      prognostic biomarker of development of clinically significant macular edema,
      whereas subclinical macular edema identified by OCT and mfERG appear to be also
      good candidates as organ-specific biomarkers of DR. Hemoglobin A1c remains the
      only confirmed systemic prognostic biomarker of DR progression. The availability
      of biomarkers of DR progression and the identification of different phenotypes of
      DR with different risks for development of vision-threatening complications
      offers new perspectives for understanding DR and for its personalized management.

PMID- 24680930
TI  - Delivery of epidrugs.
AB  - Inhibitors of epigenetic targets have entered clinical trials with some success,
      in particular for combined therapies. Like many other chemotherapeutics these new
      classes of molecules have dose-limiting toxicities and highly active metabolism
      in vivo resulting in lower efficacy than expected. This review presents drug
      delivery strategies proposed to prolong epigenetic inhibitor effects while
      reducing toxicities and metabolic clearance. Inspired from the work done in
      cancer-targeted strategies, prodrugs and nanoparticle-based drug delivery systems
      are discussed in a comprehensive way, detailing the chemical and physiological
      principles of the selected releasing method and, when available, how epigenetic
      chemistry can be exploited. 

PMID- 24680931
TI  - Identification of IgG-kappa type macroprolactin found in the serum of an 8-year
      old girl.
AB  - BACKGROUND: We report a case of macroprolactin (macroPRL) in an 8-year-old girl
      complaining of an enlarged and painful breast who showed elevated PRL levels by
      enzyme immunoassay. METHODS: Size-exclusion high-performance liquid
      chromatography (HPLC) was carried out on a Superose 12 column to estimate the PRL
      molecular profile. To identify the type of immunoglobulin bound to PRL,
      immunoprecipitation reactions were performed using three types of anti-heavy
      chain antibody and two types of anti-light chain. RESULTS: PRL in the patient's
      serum was eluted at a size slightly larger than the IgG peak by size-exclusion
      HPLC on a Superose 12 column. In the immunoprecipitation reaction, the PRL
      concentration of the supernatant mixed with anti-gamma heavy chain and anti-kappa
      light chain was dramatically decreased compared to other types of antiserum.
      These results indicated that macromolecular PRL was composed of PRL and IgG
      kappa. CONCLUSION: A rare case of PRL-IgG-kappa-type complex was identified in
      the serum of the girl and the type of immunoglobulin light chain was determined
      for the first time. When encountering a child with hyperprolactinemia,
      pediatricians should take into account the possibility of macroPRL to avoid
      unnecessary investigation and/or treatment.

PMID- 24680932
TI  - Dissection of a Ciona regulatory element reveals complexity of cross-species
      enhancer activity.
AB  - Vertebrate genomes share numerous conserved non-coding elements, many of which
      function as enhancer elements and are hypothesised to be under evolutionary
      constraint due to a need to be bound by combinations of sequence-specific
      transcription factors. In contrast, few such conserved elements can be detected
      between vertebrates and their closest invertebrate relatives. Despite this lack
      of sequence identity, cross-species transgenesis has identified some cases where
      non-coding DNA from invertebrates drives reporter gene expression in transgenic
      vertebrates in patterns reminiscent of the expression of vertebrate orthologues.
      Such instances are presumed to reflect the presence of conserved suites of
      binding sites in the regulatory regions of invertebrate and vertebrate
      orthologues, such that both regulatory elements can correctly interpret the trans
      activating environment. Shuffling of binding sites has been suggested to lie
      behind loss of sequence conservation; however this has not been experimentally
      tested. Here we examine the underlying basis of enhancer activity for the Ciona
      intestinalis betagamma-crystallin gene, which drives expression in the lens of
      transgenic vertebrates despite the Ciona lineage predating the evolution of the
      lens. We construct an interactive gene regulatory network (GRN) for vertebrate
      lens development, allowing network interactions to be robustly catalogued and
      conserved network components and features to be identified. We show that a small
      number of binding motifs are necessary for Ciona betagamma-crystallin expression,
      and narrow down the likely factors that bind to these motifs. Several of these
      overlap with the conserved core of the vertebrate lens GRN, implicating these
      sites in cross species function. However when we test these motifs in a
      transgenic vertebrate they prove to be dispensable for reporter expression in the
      lens. These results show that current models depicting cross species enhancer
      function as dependent on conserved binding sites can be overly simplistic, with
      sound evolutionary inference requiring detailed dissection of underlying
      mechanisms. 

PMID- 24680933
TI  - Efficient production of lycopene in Saccharomyces cerevisiae by expression of
      synthetic crt genes from a plasmid harboring the ADH2 promoter.
AB  - Lycopene is an effective antioxidant proposed as a possible treatment for some
      cancers and other degenerative human conditions. This study aims at generation of
      a yeast strain (Saccharomyces cerevisiae) of efficient productivity of lycopene
      by overexpressing synthetic genes derived from crtE, crtB and crtI genes of
      Erwinia uredovora. These synthetic genes were constructed in accordance with the
      preferred codon usage in S. cerevisiae but with no changes in amino acid
      sequences of the gene products. S. cerevisiae cells were transformed with these
      synthetic crt genes, whose expression was regulated by the ADH2 promoter, which
      is de-repressed upon glucose depletion. The RT-PCR and Western blotting analyses
      indicated that the synthetic crt genes were efficiently transcribed and
      translated in crt-transformed S. cerevisiae cells. The highest level of lycopene
      in one of the transformed lines was 3.3mglycopene/g dry cell weight, which is
      higher than the previously reported levels of lycopene in other microorganisms
      transformed with the three genes. These results suggest the excellence of using
      the synthetic crt genes and the ADH2 promoter in generation of recombinant S.
      cerevisiae that produces a high level of lycopene. The level of ergosterol was
      reversely correlated to that of lycopene in crt-transformed S. cerevisiae cells,
      suggesting that two pathways for lycopene and ergosterol syntheses compete for
      the use of farnesyl diphosphate. 

PMID- 24680934
TI  - The prevalence of erosive osteoarthritis in carpometacarpal joints and its
      clinical burden in symptomatic community-dwelling adults.
AB  - OBJECTIVE: To estimate the prevalence of erosive disease in first carpometacarpal
      joints (CMCJs) and investigate its clinical impact compared with radiographic
      thumb base (TB) osteoarthritis (OA). PATIENT AND METHODS: Standardized
      assessments with hand radiographs were performed in participants of two
      population-based cohort studies in North Staffordshire with hand symptoms lasting
      >=1 day in the past month. Erosive disease was defined as the presence of eroded
      or remodeled phase in >=1 interphalangeal joint (IPJ) or first CMCJ following the
      Verbruggen-Veys classification. Hand pain and function were assessed with
      Australian/Canadian Hand Osteoarthritis Index (AUSCAN). Prevalence was estimated
      by dividing the number of persons with erosive lesions by population size. Linear
      and logistic regression analyses were used to contrast clinical determinants
      between persons with erosions and with radiographic TB OA. Results were presented
      as mean differences and odds ratios (ORs) with 95% confidence intervals (95% CI),
      adjusted for age, sex and radiographic severity. RESULTS: 1,076 participants were
      studied (60% women, mean age 64.7 years (SD 8.3); 24 persons had erosive disease
      in the TB. The prevalence of erosive disease in first CMCJs was 2.2% (95% CI 1.4,
      3.3). Only 0.5% (95% CI 0.2, 1.2) had erosive disease affecting IPJs and first
      CMCJs combined. More persons with erosive disease of first CMCJs reported pain in
      their TB than persons with radiographic TB OA, AUSCAN pain and function scores
      were similar. CONCLUSION: Erosive disease of first CMCJs was present in 2.2% of
      subjects with hand pain and was often not accompanied by erosions in IPJs.
      Erosive disease was associated with TB pain, but not with the level of pain, when
      compared with radiographic TB OA.

PMID- 24680935
TI  - Cigarette smoking and risk of total knee replacement for severe osteoarthritis
      among Chinese in Singapore--the Singapore Chinese health study.
AB  - PURPOSE: Data on the effects of cigarette smoking with osteoarthritis (OA) are
      inconsistent and no study has examined the effect of smoking cessation. We
      examined smoking status, duration, dosage and cessation in association with risk
      of total knee replacement (TKR) for severe knee OA among elderly Chinese in
      Singapore. METHODS: We used data from the Singapore Chinese Health Study, a
      population-based prospective cohort of 63,257 Chinese men and women aged 45-74
      years during enrollment between 1993 and 1998. Detailed information on smoking,
      current diet and lifestyle factors were obtained through in person interviews. As
      of 31 December 2011, 1,973 incident TKR cases for severe knee OA had been
      identified via linkage with nationwide hospital discharge database. We used Cox
      regression methods to examine smoking in relation to TKR risk with adjustment for
      age, gender, education, body mass index (BMI), comorbidities and physical
      activity level. RESULTS: Compared to never smokers, current smokers had a 51%
      decrease in risk of TKR [Hazards ratio (HR) = 0.49; 95% confidence interval (CI)
      = 0.40-0.60]. Among current smokers, there was a very strong dose-dependent
      association between increasing duration and dosage of smoking with decreasing
      risk of TKR (P for trend <0.0001). Among former smokers, there was a dose
      dependent response between decrease in duration of smoking cessation and
      reduction in TKR risk (P for trend = 0.034). CONCLUSION: Our findings strongly
      implicate smoking as a protective factor for TKR indicated for severe knee OA.
      This concurs with experimental data that nicotine promotes proliferation and
      collagen synthesis in chondrocytes.

PMID- 24680936
TI  - NDEL1 was decreased in the CA3 region but increased in the hippocampal blood
      vessel network during the spontaneous seizure period after pilocarpine-induced
      status epilepticus.
AB  - Nuclear distribution factor E homolog like 1 (NDEL1) plays an important role in
      mitosis, neuronal migration, and microtubule organization during brain
      development by binding to disrupted-in-schizophrenia-1 (DISC1) or lissencephaly
      (LIS1). Although some evidence has suggested that DISC1 expression is altered in
      epilepsy, few studies have reported the relationship between NDEL1 and the
      etiology of epilepsy. In present study, we first investigated the expression of
      NDEL1 and its binding protein DISC1 after pilocarpine-induced epilepsy in male
      C57BL/6 mice. Data revealed that the mRNA and protein expression of NDEL1 and
      DISC1 in the whole hippocampus increased during the spontaneous seizure period
      after status epilepticus (SE). Interestingly, however, the expression of NDEL1
      was decreased in the cornu ammonis 3 (CA3) and dentate gyrus (DG) regions.
      Moreover, SE also increased the number of blood vessels that fed the CA3 and DG
      regions of the hippocampus and increased the incidence of abnormalities in
      capillary network formation where NDEL1 protein was expressed positively.
      Meanwhile, the expression of phosphorylated ERK (p-ERK) was also increased during
      the spontaneous seizure period, with a similar expression pattern as NDEL1 and
      DISC1. Based on these results, we hypothesize that NDEL1 might interact with
      DISC1 to activate ERK signaling and function as a potential protective factor
      during the spontaneous seizure period after pilocarpine-induced SE. 

PMID- 24680937
TI  - Diosmin protects against cerebral ischemia/reperfusion injury through activating
      JAK2/STAT3 signal pathway in mice.
AB  - BACKGROUND AND OBJECT: Apoptosis is a major form of cell death in cerebral
      ischemia/reperfusion (I/R) pathogenesis and may represent a target for treatment.
      Diosmin (DM), a micronized purified flavonoid drug, possesses an anti-apoptotic
      effect in the treatment of varicose veins and renal injury. However, the effect
      of DM in the acute phase of cerebral I/R is not clear. This study investigated
      DM's role in cerebral I/R and its potential mechanism. METHODS: Male CD-1 mice
      were subjected to transient middle cerebral artery occlusion (tMCAO). Experiment
      1 was used to evaluate the time course expression of Janus tyrosine kinase-2
      (JAK2), signal transducer and activator of transcription-3 (STAT3),
      phosphorylated JAK2 (pJAK2) and phosphorylated STAT3 (pSTAT3) after cerebral I/R,
      and six time points were included. In experiment 2, DM was given orally at doses
      of 50mg/kg or 100mg/kg for 6 consecutive days before receiving tMCAO. At 24h
      after reperfusion, neurological deficit, Nissl staining, brain water content and
      infarct volume were examined. Bcl-2, Bax, pJAK2, and pSTAT3 were detected by
      immunohistochemistry, qRT-PCR and Western blot. Confocal microscope was used to
      observe the location of pSTAT3 in the cerebral cortex. RESULTS: Compared with
      Vehicle group, the high dose of DM significantly alleviated neurological deficit,
      brain water content, infarct volume, increased the Nissl-positive cells,
      upregulated the expression of pJAK2, pSTAT3 and Bcl-2 and downregulated Bax
      (P<0.05). CONCLUSION: These results showed that DM protected against cerebral I/R
      injury through activating JAK2/STAT3 signal pathway.

PMID- 24680938
TI  - Activation of prelimbic 5-HT1A receptors produces antidepressant-like effects in
      a unilateral rat model of Parkinson's disease.
AB  - Depression is a common symptom in Parkinson's disease (PD), but its
      pathophysiology remains unclear. Several lines of studies have revealed that the
      prelimbic (PrL) sub-region of the ventral medial prefrontal cortex and 5-HT1A
      receptors are involved in the regulation of depression. In this study, we
      examined whether complete unilateral lesions of the medial forebrain bundle (MFB)
      using 6-hydroxydopamine in rats are able to induce depressive-like behaviors, the
      role of PrL 5-HT1A receptors in the regulation of these behaviors, and co
      localization of 5-HT1A receptor and neuronal glutamate transporter EAAC1
      immunoreactive (EAAC1-ir) neurons in the PrL. The MFB lesions induced depressive
      like responses as measured by the sucrose preference and forced swim tests when
      compared to sham-operated rats. The intra-PrL injection of 5HT1A receptor agonist
      8-OH-DPAT (50, 100, and 500ng/rat) increased sucrose consumption, and decreased
      immobility time in both sham-operated and the lesioned rats, indicating the
      induction of antidepressant effects. Furthermore, the intra-PrL injection of
      5HT1A receptor antagonist WAY-100635 (60, 120, and 240ng/rat) showed a decrease
      in sucrose consumption, and an increase in immobility time, indicating the
      induction of depressive-like responses. However, the effective doses in the
      lesioned rats were higher than those in sham-operated rats, which attribute to
      down-regulation of 5-HT1A receptor expression on EAAC1-ir neurons in the PrL of
      the lesioned rats. These findings suggest that unilateral lesions of the MFB in
      rats may induce depressive-like behaviors, and 5-HT1A receptors of the PrL play
      an important role in the regulation of these behaviors. 

PMID- 24680939
TI  - Impaired CBF regulation and high CBF threshold contribute to the increased
      sensitivity of spontaneously hypertensive rats to cerebral ischemia.
AB  - The correlation between temporal changes of regional cerebral blood flow (rCBF)
      and the severity of transient ischemic stroke in spontaneously hypertensive rats
      (SHR) and Wistar-Kyoto rats (WKY) was investigated using T2-, diffusion- and
      perfusion-weighted magnetic resonance imaging at six different time points:
      before and during 1h of unilateral middle cerebral artery occlusion (MCAO), 1h
      after reperfusion, and 1 day, 4 days and 7 days after MCAO. rCBF values were
      measured in both hemispheres, and the perfusion-deficient lesion (PDL) was
      defined as the area of the brain with a 57% or more reduction in basal CBF.
      Within the PDL, regions were further refined as ischemic core (rCBF=0-6 mL/100
      g/min), ischemic penumbra (rCBF=6-15 mL/100 g/min) and benign oligemia (rCBF>15
      mL/100 g/min). SHR and WKY had identical initial volume of the PDLs (WKY: 32.52
      +/- 4.08% vs. SHR: 33.95 +/- 3.68%; P>0.05) and the maximum rCBF measured within
      those lesions (WKY: 38.20 +/- 3.57 mL/100g/min vs. SHR: 38.46 +/- 6.22 mL/100
      g/min; P>0.05) during MCAO. However, in SHR virtually all of the PDL progressed
      to become the final ischemic lesion (33.02 +/- 5.41%, P>0.05), while the final
      ischemic lesion volume of WKY (12.62 +/- 9.19%) was significantly smaller than
      their original PDL (P<0.01) and similar to the ischemic core (13.13 +/- 2.96%,
      P>0.05). The region with the lowest range of rCBF was positively correlated with
      the final ischemic lesion volume (r=0.716, P<0.01). Both during ischemia and
      after reperfusion, rCBF in either ipsilesional and contralesional brain
      hemispheres of SHR could not be restored to pre-ischemic levels, and remained
      lower than in WKY until up to 4 days after MCAO. The data suggest that impaired
      CBF regulation and relatively high CBF threshold for ischemia are strong
      contributors to the increased susceptibility of SHR to ischemic stroke.

PMID- 24680941
TI  - Emergency ventilation with a Chevalier Jackson's metal tracheostomy tube.
AB  - Chevalier Jackson's metal tracheostomy tube is the oldest tracheostomy tube and
      has survived to the present day. This is probably because it is easy to use and
      cost-effective. However its biggest limitation is that it lacks provision to
      connect to a ventilating circuit in an emergency. Here we describe a simple and
      effective technique for ventilation with Chevalier Jackson's metal tracheostomy
      tube. Ventilation can be achieved by connecting the tracheostomy tube to an
      appropriate size universal 15mm endotracheal tube connector. We have also worked
      out a formula for selection of appropriate connector for various sizes of
      tracheostomy tube. 

PMID- 24680940
TI  - Spinal nNOS regulates phrenic motor facilitation by a 5-HT2B receptor- and NADPH
      oxidase-dependent mechanism.
AB  - Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF) by
      a mechanism that requires spinal serotonin (5-HT) receptor activation and NADPH
      oxidase (NOX) activity. Here, we investigated whether: (1) spinal nitric oxide
      synthase (NOS) activity is necessary for AIH-induced pLTF; (2) episodic exogenous
      nitric oxide (NO) is sufficient to elicit phrenic motor facilitation (pMF)
      without AIH (i.e. pharmacologically); and (3) NO-induced pMF requires spinal 5
      HT2B receptor and NOX activation. In anesthetized, mechanically ventilated adult
      male rats, AIH (3 * 5-min episodes; 10% O2; 5 min) elicited a progressive
      increase in the amplitude of integrated phrenic nerve bursts (i.e. pLTF), which
      lasted 60 min post-AIH (45.1 +/- 8.6% baseline). Pre-treatment with intrathecal
      (i.t.) injections of a neuronal NOS inhibitor (nNOS-inhibitor-1) near the phrenic
      motor nucleus attenuated pLTF (14.7 +/- 2.5%), whereas an inducible NOS (iNOS)
      inhibitor (1400 W) had no effect (56.3 +/- 8.0%). Episodic i.t. injections (3 *
      5MUl volume; 5 min) of a NO donor (sodium nitroprusside; SNP) elicited pMF
      similar in time-course and magnitude (40.4 +/- 6.0%, 60 min post-injection) to
      AIH-induced pLTF. SNP-induced pMF was blocked by a 5-HT2B receptor antagonist
      (SB206553), a superoxide dismutase mimetic (MnTMPyP), and two NOX inhibitors
      (apocynin and DPI). Neither pLTF nor pMF was affected by pre-treatment with a
      protein kinase G (PKG) inhibitor (KT-5823). Thus, spinal nNOS activity is
      necessary for AIH-induced pLTF, and episodic spinal NO is sufficient to elicit
      pMF by a mechanism that requires 5-HT2B receptor activation and NOX-derived ROS
      formation, which indicates AIH (and NO) elicits spinal respiratory plasticity by
      a nitrergic-serotonergic mechanism.

PMID- 24680942
TI  - IL-17 promotes Type 1 T cell response through modulating dendritic cell function
      in acute allograft rejection.
AB  - IL-17 is a cytokine that produced by various type of cell. Previous studies have
      been shown that IL-17 plays a critical role in the pathogenesis of different
      diseases. However, few studies have addressed the source and mechanism of IL-17
      in the development of allograft rejection response. In this study, we present
      that the IL-17 expression reaches the strongest response at the early stage of
      cardiac allograft rejection, and was elevated earlier than DC maturation. The IL
      17 is predominantly produced by CD3(+) T cells, whereas CD11c, CD11b, and NK1.1
      positive cells rarely expressed IL-17. It is worth noting that blockade of
      endogenous IL-17 activity suppressed DC maturation, decreased inflammatory
      cytokines and impaired Th1 immune response during acute allograft rejection.
      Furthermore, adoptive transfer with DCs from IL-17-treated mice had a significant
      longer allograft survival time and decreased number of IFN-gamma produced by T
      cells. Consistently, in an in vitro experiment, recombinant IL-17 significantly
      up-regulate co-stimulatory molecules of bone marrow derived dendritic cells
      (BMDCs), and IL-17-treated BMDCs show that an increased capacity to enhance T
      cell function was also observed. In conclusion, our data provide clear evidence
      that the early elevated level of IL-17 contributes to allograft rejection through
      modulating dendritic cell function. 

PMID- 24680943
TI  - Ginsenoside Re as an adjuvant to enhance the immune response to the inactivated
      rabies virus vaccine in mice.
AB  - The inactivated rabies virus vaccine (RV) is a relatively expensive vaccine,
      prone to failure in some cases. Ginsenoside Re (Re) is a saponin isolated from
      Panax ginseng, and has an adjuvant property. Here the adjuvant effect of Re to
      improve the immune response to the RV is evaluated in mice. ICR mice were
      immunized with saline, 2.50mg/kg Re, 20MUl RV, 100MUl RV, or 20MUl of RV
      adjuvanted with Re (1.25, 2.50 or 5.00mg/kg). Different time points after
      boosting, we measured serum antibodies in blood samples and separated splenocytes
      to detect lymphocyte proliferation and the production of IL-4, IL-10, IL-12, and
      IFN-gamma in vitro. We also compared immunizations containing 20MUl RV and 20MUl
      RV adjuvanted with Re (5.00mg/kg) for the expression of CD4(+) and CD8(+) T-cell
      subsets at different time points. Results indicated that co-administration of Re
      significantly enhanced serum antibody titers, increased the CD4(+):CD8(+) ratio,
      and enhanced both proliferation responses and IL-4, IL-10, IL-12 and IFN-gamma
      secretions. Both Th1 and Th2 immune responses were activated. The supplementation
      of the Re (5.00mg/kg) to 20MUl of RV significantly amplified serum antibody
      responses and Th1/Th2 responses inducing similar protection as did 100MUl of RV.
      This suggests that Re could be used to reduce the dose, and therefore the cost,
      of the RV to achieve the same effective protection. Re merits further studies for
      use with vaccines of mixed Th1/Th2 immune responses. 

PMID- 24680944
TI  - The distortion of gradient profiles in reversed-phase liquid chromatography.
AB  - Severe distortions of the axial concentration profiles of modifiers in steep RPLC
      gradients were recently observed. These distortions are directly explained by the
      results of measurements of the excess adsorption isotherms of the strongest
      mobile phase component, the concentration of which is made to increase linearly
      with time at the column inlet. A front shock or a discontinuity of the organic
      modifier concentration may arise and grow along the column. The position where it
      forms is determined by the reciprocal of the second derivative of the excess
      adsorption isotherm with respect to the concentration of the strongest mobile
      phase component. It forms when two characteristic lines intersect for the first
      time. Gradient profiles are continuous and diffuse as long as characteristic
      lines do not intersect but diverge from each other. However, acetonitrile-water
      gradients are systematically distorted and deviate significantly from assumed
      ideal, linear, non-retained gradients. This challenges the validity of classical
      theories of gradient chromatography regarding the prediction of retention times,
      peak widths, and band compression factors when steep gradients are applied.

PMID- 24680945
TI  - Precision evaluation of chiral capillary electrophoretic methods in the context
      of inter-instrumental transfer: constant current versus constant voltage
      application.
AB  - Capillary electrophoresis (CE) is an electrophoretic separation technique that
      was rapidly increasing in popularity some years ago and that led to high
      expectations. Because of their different separation mechanisms, CE and HPLC are
      alternative and complementary separation techniques. Chiral molecules can be
      directly separated with CE by simply adding a chiral selector to the running
      buffer solution, leading to flexible and cheap methods. Major drawbacks of
      capillary electrophoretic separation methods are, however, the lower precision
      compared to HLPC methods and a more problematic analytical method transfer. Both
      above stated disadvantages limit the generalized use of CE methods in the
      pharmaceutical industry. Multiple solutions have been suggested to improve the
      precision of CE methods. In this work the application of a constant current
      during the electrophoretic separation instead of the more commonly used
      application of a constant voltage was studied on two CE instruments with
      different cooling mechanisms. This was done in the context of optimizing method
      transfer conditions. A constant current may reduce the generation of heat in the
      capillary and the consequentially radial and axial temperature fluctuations that
      both negatively influence the precision of the peak areas, migration times and
      resolutions of a CE method. The repeatability and time-different intermediate
      precision of both electrophoretic separation modes were compared on two different
      CE instruments after a successful analytical method transfer. The chiral
      separations of three beta-blockers, propranolol, sotalol and betaxolol, were used
      as test cases. A constant current led to a general improvement of the
      repeatability and time-different intermediate precision of the relative Area
      Under the Curve of all three beta-blockers, while that of the migration times
      remained rather constant. It also led to more similar electropherograms than the
      application of a constant voltage. 

PMID- 24680946
TI  - 3D geometric split-merge segmentation of brain MRI datasets.
AB  - In this paper, a novel method for MRI volume segmentation based on region
      adaptive splitting and merging is proposed. The method, called Adaptive Geometric
      Split Merge (AGSM) segmentation, aims at finding complex geometrical shapes that
      consist of homogeneous geometrical 3D regions. In each volume splitting step,
      several splitting strategies are examined and the most appropriate is activated.
      A way to find the maximal homogeneity axis of the volume is also introduced.
      Along this axis, the volume splitting technique divides the entire volume in a
      number of large homogeneous 3D regions, while at the same time, it defines more
      clearly small homogeneous regions within the volume in such a way that they have
      greater probabilities of survival at the subsequent merging step. Region merging
      criteria are proposed to this end. The presented segmentation method has been
      applied to brain MRI medical datasets to provide segmentation results when each
      voxel is composed of one tissue type (hard segmentation). The volume splitting
      procedure does not require training data, while it demonstrates improved
      segmentation performance in noisy brain MRI datasets, when compared to the state
      of the art methods. 

PMID- 24680947
TI  - An overview of FDA-approved new molecular entities: 1827-2013.
AB  - The pharmaceutical industry is undergoing fundamental change and its future is
      unclear. We performed a meta-analysis by cataloging FDA-approved legacy drugs and
      new molecular entities (NMEs). Objective information regarding scientific,
      medical and commercial activities was captured and provides insight into
      processes governing drug development. In this report, we review the rates of NME
      introduction through to the end of 2013. Recent trends show the emergence of a
      handful of companies that controls two-thirds of NMEs. We also report growth in
      the number of NMEs controlled by marketing organizations that have little or no
      internal drug discovery or development activities. This trend has increased
      dramatically since 2000 and could raise important questions about the future
      landscape and viability of drug discovery and development. 

PMID- 24680948
TI  - The first characterization of two type I interferons in turbot (Scophthalmus
      maximus) reveals their differential role, expression pattern and gene induction.
AB  - Type I interferons (IFNs) are considered the main cytokines directing the
      antiviral immune response in vertebrates. These molecules are able to induce the
      transcription of interferon-stimulated genes (ISGs) which, using different
      blocking mechanisms, reduce the viral proliferation in the host. In addition, a
      contradictory role of these IFNs in the protection against bacterial challenges
      using murine models has been observed, increasing the survival or having a
      detrimental effect depending on the bacteria species. In teleosts, a variable
      number of type I IFNs has been described with different expression patterns,
      protective capabilities or gene induction profiles even for the different IFNs
      belonging to the same species. In this work, two type I IFNs (ifn1 and ifn2) have
      been characterized for the first time in turbot (Scophthalmus maximus), showing
      different properties. Whereas Ifn1 reflected a clear antiviral activity (over
      expression of ISGs and protection against viral haemorrhagic septicaemia virus),
      Ifn2 was not able to induce this response, although both transcripts were up
      regulated after viral challenge. On the other hand, turbot IFNs did not show any
      protective effect against the bacteria Aeromonas salmonicida, although they were
      induced after bacterial challenge. Both IFNs induced the expression of several
      immune genes, but the effect of Ifn2 was mainly limited to the site of
      administration (intramuscular injection). Interestingly, Ifn2 but not Ifn1
      induced an increase in the expression level of interleukin-1 beta (il1b).
      Therefore, the role of Ifn2 could be more related with the immune regulation,
      being involved mainly in the inflammation process. 

PMID- 24680949
TI  - Management of patients diagnosed with atypical ductal hyperplasia by vacuum
      assisted core biopsy: a prospective assessment of the guidelines used at our
      institution.
AB  - BACKGROUND: Because of underestimation, surgical excision is recommended for
      atypical ductal hyperplasia diagnosed on directional vacuum-assisted biopsies.
      The following guidelines have been established according to our retrospective
      study published in 2008: excision for lesions >= 21 mm, follow-up for lesions <6
      mm with complete removal of microcalcifications, and follow-up or excision for 6
      to 21-mm lesions with respectively less or >2 atypical ductal hyperplasia foci.
      METHODS AND RESULTS: These guidelines were assessed in a prospective series of
      124 patients with a median follow-up of 30 months. Conformity rate was 92%.
      Upgrading was 28% (15 of 53 patients) for conformed surgery and absent for
      surgery performed beyond the scope of guidelines. For the patients with benign
      result at surgery (n = 38) or just followed (n = 61), 3 cancers occurred in
      either breast at 1 to 3 years. CONCLUSIONS: These convenient guidelines can
      safely spare surgery for a subset of patients. However, annual mammographic
      follow-up is recommended since the risk of subsequent cancer remains high for
      both breasts.

PMID- 24680950
TI  - Silicon microfluidic flow focusing devices for the production of size-controlled
      PLGA based drug loaded microparticles.
AB  - The increasing realisation of the impact of size and surface properties on the
      bio-distribution of drug loaded colloidal particles has driven the application of
      micro fabrication technologies for the precise engineering of drug loaded
      microparticles. This paper demonstrates an alternative approach for producing
      size controlled drug loaded PLGA based microparticles using silicon Microfluidic
      Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of
      the flow focusing channel, microparticle size was successfully optimised by
      modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase
      (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 MUm and
      were highly monodisperse (coefficient of variation <5%). A comparison of
      Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional
      production techniques was also performed. MFFDs produced microparticles with a
      narrower size distribution profile, relative to the conventional approaches. In
      vitro release kinetics of CsA was found to be influenced by the production
      technique, with the MFFD approach demonstrating the slowest rate of release over
      7 days (4.99 +/- 0.26%). Finally, MFFDs were utilised to produce pegylated
      microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth
      microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly
      porous surface morphology and rapid CsA release, with 85 +/- 6.68% CsA released
      after 24h. The findings from this study demonstrate the utility of silicon MFFDs
      for the precise control of size and surface morphology of PLGA based
      microparticles with potential drug delivery applications.

PMID- 24680951
TI  - Targeted poly (L-gamma-glutamyl glutamine) nanoparticles of docetaxel against
      folate over-expressed breast cancer cells.
AB  - A novel folate (FA) conjugated poly(l-gamma-glutamyl glutamine) (PGG)
      nanoparticle loaded with docetaxel (DTX) was prepared to take advantage of both
      targeted drug delivery in breast cancer and reducing the overall side effects due
      to the adjuvant free formulation in comparison with Taxotere((r)).
      Nanoprecipitation method was employed to prepare nanoparticles (NPs). The
      chemical structure of PGG synthesized polymers and PGG-FA conjugates and
      polymeric nanoparticles were characterized by H NMR, FTIR spectroscopy, field
      emission scanning electron microscopy, and laser scanning confocal microscopy.
      The average size of optimized nanoparticles with the aid of Box-Behnken
      experimental design was 131.96 +/- 5.34(nm) with polydispersity of 0.089 +/-
      0.019, zeta potential of -25.8 +/- 2.21(mV), and entrapment efficiency of 67.83
      +/- 3.29(%). In vitro cytotoxicity of the designed NPs was investigated by MTT
      assay against three chosen cell lines of MCF7, 4T1, and A549 based on their
      folate receptor expression capacity and was compared with Taxotere((r)).
      Moreover, PGG-FOL NPs were loaded with 6-coumarin for cellular uptake
      investigation. In order to assess the antitumor efficacy and biodistribution of
      targeted NPs, 4T1 murine breast tumors were established on the balb/c mice and in
      vivo studies were performed. The obtained results showed that the novel designed
      system was highly effective against tumor cells and successfully localized in the
      tumor site.

PMID- 24680952
TI  - Potentiation by caffeine of cytogenetic damage induced by steroidal derivatives
      in human lymphocytes in vitro.
AB  - We studied the effects of three newly synthesized steroidal derivatives of
      nitrogen mustards, alone or in combination with caffeine, on sister chromatid
      exchange (SCE) frequencies and on human lymphocyte proliferation kinetics. The
      agents have as alkylator functionalities either P-N,N-bis(2
      chloroethyl)aminophenyl-buturate (CHL) or P-N,N-bis(2-chloroethyl)aminophenyl
      acetate (PHE), esterified with a modified steroidal nucleus. An enhancement of
      SCE frequency was seen with compounds which contain either PHE or CHL as
      alkylators and are esterified with a steroidal nucleus having added a cholestene
      group in the 17-position of the D-ring. The exocyclic insertion of an -NHCO-
      group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of
      PHE) gave a compound showing increased SCE frequency. Enhanced cytogenetic damage
      was observed when lymphocytes were exposed in vitro to caffeine. The compounds,
      alone or in combination with caffeine, caused a concentration-dependent increase
      in SCE frequencies and cell division delays, and caffeine was found to act
      synergistically with the steroidal alkylators. 

PMID- 24680953
TI  - Low-dose combination of Rho kinase and L-type Ca(2+) channel antagonists for
      selective inhibition of depolarization-induced sustained arterial contraction.
AB  - L-type Ca(2+) channels (LTCCs) are involved in the maintenance of tonic arterial
      contractions and regulate the RhoA/Rho-associated kinase (ROCK) sensitization
      cascade. We have tested effects of individual and combined low concentrations of
      LTCCs and ROCK inhibitors to produce arterial relaxation without the adverse side
      effects of LTCCs antagonists. We have also studied whether this pharmacological
      strategy alters Ca(2+)-dependent electrical properties of isolated arterial and
      cardiac myocytes as well as cardiac contractility. Rat basilar, human carotid and
      coronary arterial rings were mounted on a small-vessel myograph to measure
      isometric tension and cardiac contractility was measured in Langendorff-perfused
      rat heart. Simultaneous cytosolic Ca(2+) concentration and arterial diameter were
      measured in intact pressurized arteries loaded with Fura-2. Patch-clamp
      techniques were used to measure electrical properties in isolated cardiac and
      arterial myocytes. Low concentrations of LTCCs and ROCK inhibitors reduced the
      tonic component of moderate depolarization-evoked contraction, leaving the phasic
      component practically unaltered. This selective vasorelaxant effect was more
      marked when the LTCCs and ROCK inhibitors were applied together. In the
      concentration range used (nM), Ca(2+) currents in arterial myocytes, cardiac
      action potentials and heart contractility were unaffected by this pharmacological
      approach. In conclusion, low doses of LTCCs and ROCK inhibitors could be used to
      selectively relax precontracted arteries in pathologic conditions such as
      hypertension, and cerebral or coronary spasms with minor side effects on
      physiological contractile properties of vascular and cardiac myocytes. 

PMID- 24680954
TI  - Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and
      infectivity.
AB  - Dengue virus serotypes 1-4 (DENV1-4) are transmitted by mosquitoes which cause
      most frequent arboviral infections in the world resulting in ~390 million cases
      with ~25,000 deaths annually. There is no vaccine or antiviral drug currently
      available for human use. Compounds containing quinoline scaffold were shown to
      inhibit flavivirus NS2B-NS3 protease (NS2B-NS3pro) with good potencies. In this
      study, we screened quinoline derivatives, which are known antimalarial drugs for
      inhibition of DENV2 and West Nile virus (WNV) replication using the corresponding
      replicon expressing cell-based assays. Amodiaquine (AQ), one of the 4
      aminoquinoline drugs, inhibited DENV2 infectivity measured by plaque assays, with
      EC50 and EC90 values of 1.08+/-0.09MUM and 2.69+/-0.47 MUM, respectively, and
      DENV2 RNA replication measured by Renilla luciferase reporter assay, with EC50
      value of 7.41+/-1.09MUM in the replicon expressing cells. Cytotoxic concentration
      (CC50) in BHK-21 cells was 52.09+/-4.25MUM. The replication inhibition was
      confirmed by plaque assay of the extracellular virions as well as by qRT-PCR of
      the intracellular and extracellular viral RNA levels. AQ was stable for at least
      96h and had minor inhibitory effect on entry, translation, and post-replication
      stages in the viral life cycle. DENV protease, 5'-methyltransferase, and RNA
      dependent RNA polymerase do not seem to be targets of AQ. Both p-hydroxyanilino
      and diethylaminomethyl moieties are important for AQ to inhibit DENV2 replication
      and infectivity. Our results support AQ as a promising candidate for anti
      flaviviral therapy. 

PMID- 24680955
TI  - Evaluation of luciferase and GFP-expressing Nipah viruses for rapid quantitative
      antiviral screening.
AB  - Nipah virus (NiV) outbreaks have occurred in Malaysia, India, and Bangladesh, and
      the virus continues to cause annual outbreaks of fatal human encephalitis in
      Bangladesh due to spillover from its bat host reservoir. Due to its high
      pathogenicity, its potential use for bio/agro-terrorism, and to the current lack
      of approved therapeutics, NiV is designated as an overlap select agent requiring
      biosafety level-4 containment. Although the development of therapeutic monoclonal
      antibodies and soluble protein subunit vaccines have shown great promise, the
      paucity of effective antiviral drugs against NiV merits further exploration of
      compound libraries using rapid quantitative antiviral assays. As a proof-of
      concept study, we evaluated the use of fluorescent and luminescent reporter NiVs
      for antiviral screening. We constructed and rescued NiVs expressing either
      Renilla luciferase or green fluorescent protein, and characterized their reporter
      signal kinetics in different cell types as well as in the presence of several
      inhibitors. The 50% effective concentrations (EC50s) derived for inhibitors
      against both reporter viruses are within range of EC50s derived from virus yield
      based dose-response assays against wild-type NiV (within 1Log10), thus
      demonstrating that both reporter NiVs can serve as robust antiviral screening
      tools. Utilizing these live NiV-based reporter assays requires modest
      instrumentation, and circumvents the time and labor-intensive steps associated
      with cytopathic effect or viral antigen-based assays. These reporter NiVs will
      not only facilitate antiviral screening, but also the study of host cell
      components that influence the virus life cycle. 

PMID- 24680956
TI  - The multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication
      by regulating IRES-dependent translation of viral proteins.
AB  - The activation of ERK and p38 signal cascade in host cells has been demonstrated
      to be essential for picornavirus enterovirus 71 (EV71) replication and up
      regulation of virus-induced cyclooxygenase-2 (COX-2)/prostaglandins E2 (PGE2)
      expression. The aim of this study was to examine the effects of sorafenib, a
      clinically approved anti-cancer multi-targeted kinase inhibitor, on the
      propagation and pathogenesis of EV71, with a view to its possible mechanism and
      potential use in the design of therapy regimes for Hand foot and mouth disease
      (HFMD) patients with life threatening neurological complications. In this study,
      non-toxic concentrations of sorafenib were shown to inhibit the yield of
      infectious progeny EV71 (clinical BC08 strain) by about 90% in three different
      cell types. A similar inhibitory effect of sorafenib was observed on the
      synthesis of both viral genomic RNA and the VP1 protein. Interestingly, sorafenib
      exerted obvious inhibition of the EV71 internal ribosomal entry site (IRES)
      mediated translation, the first step in picornavirus replication, by linking it
      to a firefly luciferase reporter gene. Sorafenib was also able to prevent both
      EV71-induced CPE and the activation of ERK and p38, which contributes to up
      regulation COX-2/PGE2 expression induced by the virus. Overall, this study shows
      that sorafenib strongly inhibits EV71 replication at least in part by regulating
      viral IRES-dependent translation of viral proteins, indicating a novel potential
      strategy for the treatment of HFMD patients with severe neurological
      complications. To our knowledge, this is the first report that investigates the
      mechanism by which sorafenib inhibits EV71 replication. 

PMID- 24680957
TI  - Substituted 2,6-bis(benzimidazol-2-yl)pyridines: a novel chemical class of
      pestivirus inhibitors that targets a hot spot for inhibition of pestivirus
      replication in the RNA-dependent RNA polymerase.
AB  - 2,6-Bis(benzimidazol-2-yl)pyridine (BBP/CSFA-0) was identified in a CPE-based
      screening as a selective inhibitor of the in vitro bovine viral diarrhea virus
      (BVDV) replication. The EC50-values for the inhibition of BVDV-induced cytopathic
      (CPE) effect, viral RNA synthesis and the production of infectious virus were
      0.3+/-0.1MUM, 0.05+/-0.01MUM and 0.3+/-0.04MUM, respectively. Furthermore,
      BBP/CSFA-0 inhibits the in vitro replication of the classical swine fever virus
      (CSFV) with an EC50 of 0.33+/-0.25MUM. BBP/CSFA-0 proved in vitro inactive
      against the hepatitis C virus, that belongs like BVDV and CSFV to the family of
      Flaviviridae. Modification of the substituents on the two 1H-benzimidazole groups
      of BBP resulted in analogues equipotent in anti-BVDV activity (EC50=0.7+/
      0.1MUM), devoid of cytotoxicity (S.I.=142). BBP resistant BVDV was selected for
      and was found to carry the I261M mutation in the viral RNA-dependent RNA
      polymerase (RdRp). Likewise, BBP-resistant CSFV was selected for; this variant
      carries either an I261N or a P262A mutation in NS5B. Molecular modeling revealed
      that I261 and P262 are located in a small cavity near the fingertip domain of the
      pestivirus polymerase. BBP-resistant BVDV and CSFV proved to be cross-resistant
      to earlier reported pestivirus inhibitors (BPIP, AG110 and LZ37) that are known
      to target the same region of the RdRp. BBP did not inhibit the in vitro activity
      of recombinant BVDV RdRp but inhibited the activity of BVDV replication complexes
      (RCs). BBP interacts likely with the fingertip of the pestivirus RdRp at the same
      position as BPIP, AG110 and LZ37. This indicates that this region is a "hot spot"
      for inhibition of pestivirus replication. 

PMID- 24680958
TI  - Pattern recognition of neurotransmitters using multimode sensing.
AB  - BACKGROUND: Pattern recognition is essential in chemical analysis of biological
      fluids. Reliable and sensitive methods for neurotransmitters analysis are needed.
      NEW METHOD: Therefore, we developed for pattern recognition of neurotransmitters:
      dopamine, epinephrine, norepinephrine a method based on multimode sensing.
      Multimode sensing was performed using microsensors based on diamond paste
      modified with 5,10,15,20-tetraphenyl-21H,23H-porphyrine, hemin and protoporphyrin
      IX in stochastic and differential pulse voltammetry modes. RESULTS: Optimized
      working conditions: phosphate buffer solution of pH 3.01 and KCl 0.1mol/L (as
      electrolyte support), were determined using cyclic voltammetry and used in all
      measurements. The lowest limits of quantification were: 10(-10)mol/L for dopamine
      and epinephrine, and 10(-11)mol/L for norepinephrine. The multimode microsensors
      were selective over ascorbic and uric acids and the method facilitated reliable
      assay of neurotransmitters in urine samples, and therefore, the pattern
      recognition showed high reliability (RSD<1% for more than 6 months) for the
      simultaneous determination of dopamine, epinephrine and norepinephrine from urine
      and whole blood samples. COMPARISON WITH EXISTING METHOD(S): The proposed method
      can perform pattern recognition of the three neurotransmitters on biological
      fluids at a lower determination level than chromatographic methods. The sampling
      of the biological fluids referees only to the buffering (1:1, v/v) with a
      phosphate buffer pH 3.01, while for chromatographic methods the sampling is
      laborious. CONCLUSIONS: Accordingly with the statistic evaluation of the results
      at 99.00% confidence level, both modes can be used for pattern recognition and
      quantification of neurotransmitters with high reliability. The best multimode
      microsensor was the one based on diamond paste modified with protoporphyrin IX.

PMID- 24680959
TI  - The interplay between individual, social, and environmental influences on
      chimpanzee food choices.
AB  - The foraging activity of chimpanzees requires individuals to balance personal
      preferences with nutrient requirements, food availability, and interactions with
      members of their social group. To determine whether chimpanzee food preferences
      are fixed or malleable across varying socio-ecological contexts, we presented six
      zoo-housed chimpanzees with pairwise combinations of four different foods under
      two experimental conditions. First, we individually tested each chimpanzee's
      choices for the four foods to ascertain individual preferences. Second, we tested
      the chimpanzees in a situation which more-closely mimicked the foraging pressures
      experienced by wild chimpanzees. In this second condition, the chimpanzees were
      tested in a group setting and the food availability was less predictable, such as
      in a patchy foraging environment. Subjects expressed significant variation in
      their selection of which foods to consume in the two different contexts and also
      appeared more willing to consume less-preferred foods in the unpredictable,
      social environment. These results suggest that chimpanzees' food preferences are
      not fixed, but change with context and are likely mediated by social
      facilitation. This is not only important to understand chimpanzees' foraging
      patterns and dietary requirements, but also has implications for experimental
      paradigms that rely on food preferences. 

PMID- 24680960
TI  - Construction and physiochemical characterisation of a multi-composite, potential
      oral vaccine delivery system (VDS).
AB  - An increasing human population requires a secure food supply and a cost
      effective, oral vaccine delivery system for livestock would help facilitate this
      end. Recombinant antigen adsorbed onto silica beads and coated with myristic
      acid, was released (~15% (w/v)) over 24 h at pH 8.8. At pH 2, the myristic acid
      acted as an enteric coating, protecting the antigen from a variety of proteases.
      The antigen adsorbed onto silica particles, coated in myristic acid had a
      conserved secondary structure (measured by circular dichroism (CD) spectroscopy)
      following its pH-triggered release. Small angle neutron scattering (SANS) was
      used to measure the thickness of the adsorbed antigen, finding that its adsorbed
      conformation was slightly greater than its solution radius of gyration, i.e. 120
      160 A. The addition of myristic acid led to a further increase in particle size,
      with scattering data consistent with an acid thickness slightly greater than a
      monolayer of fully extended alkyl chains and a degree of hydration of around 50%.
      Whilst adsorbed onto the silica and coated in myristic acid, the protein was
      stable over 14 days at 42  degrees C, indicating a reduced need for cold chain
      storage. These data indicate that further investigation is warranted into the
      development of this technology.

PMID- 24680961
TI  - Chitosan lactate wafer as a platform for the buccal delivery of tizanidine HCl:
      in vitro and in vivo performance.
AB  - Tizanidine HCl is a skeletal muscle relaxant that suffers from extensive hepatic
      metabolism resulting in 34-40% oral bioavailability. It also suffers from short
      half-life (2.1-4.2h) that necessitates frequent administration thus reducing
      patient compliance. In addition, tizanidine HCl is water soluble, so it is a
      challenging candidate for controlled drug delivery. In our study, tizanidine was
      encapsulated in chitosan lactate beads cross-linked with sodium tripolyphosphate.
      The beads were further incorporated into chitosan lactate wafer to be easily
      applied to buccal mucosa, aiming to bypass the hepatic metabolism. A central
      composite face-centered design was applied to statistically optimize the
      formulation variables; tripolyphosphate concentration, chitosan lactate
      concentration and polymer/drug ratio. The optimized formula suggested by the
      software composed of; 3.03% tripolyphosphate, 4.92% chitosan lactate and 2.13
      polymer/drug ratio. It provided encapsulation efficiency of 56.5% and controlled
      tizanidine release over 8h. It is also characterized by being mucoadhesive and
      nonirritant. Pharmacokinetic parameters of tizanidine from the optimized formula
      were compared to those of the immediate release tablet, Sirdalud((r)), as
      reference in human volunteers using a randomized crossover design. Significant
      increase was observed for Tmax and AUC(0-infinity). The increase in relative
      bioavailability of TIZ from the optimized formula was 2.27 fold.

PMID- 24680962
TI  - Brinzolamide nanocrystal formulations for ophthalmic delivery: reduction of
      elevated intraocular pressure in vivo.
AB  - Nanocrystal-based drug delivery systems provide important tools for ocular
      formulation development, especially when considering poorly soluble drugs. The
      objective of the study was to formulate ophthalmic, intraocular pressure (IOP)
      reducing, nanocrystal suspensions from a poorly soluble drug, brinzolamide (BRA),
      using a rapid wet milling technique, and to investigate their IOP reducing effect
      in vivo. Different stabilizers for the nanocrystals were screened (hydroxypropyl
      methylcellulose (HPMC), poloxamer F127 and F68, polysorbate 80) and HPMC was
      found to be the only successful stabilizer. In order to investigate both the
      effect of an added absorption enhancer (polysorbate 80) and the impact of the
      free drug in the nanocrystal suspension, formulations in phosphate buffered
      saline (PBS) at pH 7.4 and pH 4.5 were prepared. Particle size, polydispersity
      (PI), solid state (DSC), morphology (SEM) as well as dissolution behavior and the
      uniformity of the formulations were characterized. There was rapid dissolution of
      BRA (in PBS pH 7.4) from all the nanocrystal formulations; after 1 min 100% of
      the drug was fully dissolved. The effect was significantly pronounced at pH 4.5,
      where the dissolved fraction of drug was the highest. The cytotoxicity of
      nanocrystal formulations to human corneal epithelial cell (HCE-T) viability was
      tested. The effects of the nanocrystal formulations and the commercial product on
      the cell viability were comparable. The intraocular pressure (IOP) lowering
      effect was investigated in vivo using a modern rat ocular hypertensive model and
      elevated IOP reduction was seen in vivo with all the formulations. Notably, the
      reduction achieved in experimentally elevated IOP was comparable to that obtained
      with a marketed product. In conclusion, various BRA nanocrystal formulations,
      which all showed advantageous dissolution and absorption behavior, were
      successfully formulated.

PMID- 24680963
TI  - Formulation strategy and evaluation of nanocrystal piroxicam orally
      disintegrating tablets manufacturing by freeze-drying.
AB  - Piroxicam (PRX) is a non-steroidal anti-inflammatory drug characterized by a poor
      water solubility and consequently by a low oral bioavailability. In this work,
      different nanocrystal orally disintegrating tablets (ODT) were prepared to
      enhance piroxicam dissolution rate and saturation solubility. PRX nanocrystals
      were prepared by means of high pressure homogenization technique using poloxamer
      188 as stabilizer. Three different ODTs were prepared with the same
      nanosuspension using different excipients in order to study their effect on the
      PRX dissolution properties. PRX nanocrystal size and zeta potential were
      determined by photon correlation spectroscopy. Additional characterization of PRX
      nanocrystal ODT was carried out by infrared spectroscopy, X-ray powder
      diffractometry, differential scanning calorimetry. Dissolution study was
      performed in distilled water (pH 5.5) and compared with PRX coarse suspension
      ODT, PRX/poloxamer 188 physical mixture, bulk PRX samples and a PRX commercial
      ODT. All PRX nanocrystal ODT formulations showed a higher drug dissolution rate
      than coarse PRX ODT. PRX nanocrystal ODT prepared using gelatin or croscarmellose
      as excipient showed a higher PRX dissolution rate compared with the commercial
      formulation and ODT prepared using xanthan gum. Overall results confirmed that
      improved PRX dissolution rate is due to the increased surface-to-volume ratio due
      to the nanosized drug particle but also revealed the important role of different
      excipients used.

PMID- 24680964
TI  - A 70-year-old woman with dysphagia beginning 6 decades after caustic ingestion.

PMID- 24680965
TI  - Upper gastrointestinal bleed: old is not always gold.

PMID- 24680966
TI  - Is it time to recalibrate the MELD exception points attributed for
      hepatopulmonary syndrome?

PMID- 24680967
TI  - Molecular changes leading to gastric cancer: a suggestion from rare-type gastric
      tumors with GNAS mutations.

PMID- 24680968
TI  - A diagnosis that's up in the air.

PMID- 24680970
TI  - The alcoholic hepatitis histologic score: structured prognostic biopsy evaluation
      comes to alcoholic hepatitis.

PMID- 24680971
TI  - Identifying molecular factors that contribute to resolution of liver fibrosis.

PMID- 24680972
TI  - PTEN methylation involved in benzene-induced hematotoxicity.
AB  - It is well known that benzene is a hematotoxic carcinogen. PTEN promoter
      methylation is a representative example of transcriptional silencing of tumor
      suppressor genes. However, the effect of PTEN methylation on benzene-induced
      hematotoxicity has not yet been elucidated. In this study, the animal model of
      benzene hematotoxicity was successfully established. WBC significantly decreased
      in experimental groups (P < 0.01). Compared with the control group, the weight of
      rats increased slowly and even declined with increasing doses of benzene in the
      benzene-treated groups. An increase in the level of PTEN methylation was observed
      in the low dose group, and PTEN methylation level increased significantly in a
      dose-dependent manner. However, it was interesting that PTEN mRNA expression
      increased in the low dose group, but declined with increasing doses of benzene.
      The decrease of tumor suppressor function caused by PTEN methylation may be an
      important mechanism of benzene hematotoxicity. Furthermore, lymphoblast cell line
      F32 was incubated by benzene and then treated with 5-aza and TSA, alone or in
      combination. A dramatic decrease in the PTEN mRNA expression and a significant
      increase of PTEN methylation level in benzene-treated cells were also shown. PTEN
      mRNA expression was up regulated and PTEN methylation level was reduced by the
      epigenetic inhibitors, 5-aza and TSA. In conclusion, PTEN methylation is involved
      in benzene-induced hematotoxicity through suppressing PTEN mRNA expression.

PMID- 24680973
TI  - Serum cholesterol and triglyceride concentrations in diabetic patients with
      subclinical hypothyroidism.
AB  - OBJECTIVE: To assess whether subclinical hypothyroidism is associated to
      elevations in serum cholesterol and triglyceride levels in patients with type 2
      diabetes. PATIENTS AND METHODS: From a total population of 1,112 patients with
      type 2 diabetes screened for thyroid dysfunction (thyrotropin measurement), a
      group of 325 patients with normal thyroid function and another group of 29
      patients with subclinical hypothyroidism were selected. No patient had known
      dyslipidemia or was taking lipid lowering medication. RESULTS: Patients with
      subclinical hypothyroidism had serum levels of total cholesterol (4.88 +/- 0.74
      mmol/L), HDL cholesterol (1.37 +/- 0.34 mmol/L), LDL cholesterol (2.94 +/- 0.58
      mmol/L), and triglycerides (1.05 [0.88-1.41] mmol/L) that did not significantly
      differ from those found in euthyroid patients (4.79 +/- 0.83, 1.33 +/- 0.36, 2.87
      +/- 0.76, and 1.11 [0.81-1.43] mmol/L, respectively). Multiple regression
      analysis showed no association between TSH and serum lipid levels. CONCLUSION:
      These results suggest that, in our population, there are no significant
      differences in serum cholesterol and triglyceride levels between diabetic
      patients with normal and reduced thyroid function.

PMID- 24680974
TI  - Sensor augmented pump therapy in the management of type 1 diabetes complicated
      with Addison's disease prior to and during pregnancy.

PMID- 24680975
TI  - Feasibility of treating post-transplantation minimal residual disease in children
      with acute leukemia.
AB  - Outcomes are poor for patients with hematologic malignancies who experience overt
      relapse after allogeneic hematopoietic stem cell transplantation (HCT). Data on
      outcomes of post-transplantation minimal residual disease (MRD) are limited. In
      this single-institution, retrospective cohort analysis of children with acute
      leukemia and myelodysplastic syndrome, we document the pattern of relapse with a
      primary focus on outcomes of post-transplantation MRD. Forty of 93 patients (43%)
      who underwent a first allogeneic HCT and had systematic pretransplantation and
      post-transplantation MRD evaluations at +30, +60, +90, +180 days and +1 and +2
      years post-transplantation experienced relapse. The median time to relapse was
      4.8 months post-transplantation, with a median survival of 4 months post-relapse.
      Despite frequent, systematic, routine post-HCT disease restaging evaluation, 31
      patients (78%) presented with overt disease at the time of relapse. Seven
      patients with acute leukemia who had post-transplantation MRD presented at a
      median of 1 month post-transplantation. Owing to rapid disease progression or
      treatment-related mortality, there was no improvement in survival in those
      patients whose leukemia was detected in a state of MRD post-transplantation. Our
      results suggest that early intervention strategies targeting post-transplantation
      MRD for relapse prevention in acute leukemia may not be feasible.

PMID- 24680976
TI  - Immune reconstitution after allogeneic hematopoietic stem cell transplantation is
      associated with selective control of JC virus reactivation.
AB  - JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in
      immunocompromised patients. The mechanism of JCV reactivation and immunity in a
      transplanted immune system remains unclear. We prospectively studied 30 patients
      undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and
      collected blood and urine samples before HSCT and 3, 6, and 12 to 18 months after
      HSCT. Before HSCT, JCV DNA was detected in 7 of 30 urine, 5 of 30 peripheral
      blood mononuclear cells (PBMC) and 6 of 30 plasma samples. Although JC viruria
      remained stable after HSCT with detection in 5 of 21 samples, viremia was
      detected in only 1 of 22 plasma and none of 22 PBMC samples 12 to 18 months after
      HSCT. Prevalence of anti-JCV IgG was 83% before HSCT and decreased to 72% at 12
      to 18 months. Anti-JCV IgM was rarely detected. JCV-specific CD4(+) and CD8(+) T
      cell responses increased 12 to 18 months after HSCT. Although JC viruria
      correlated directly with detection of anti-JCV IgG, the cellular immune response
      to JCV measured by ELISpot was inversely correlated with anti-JCV IgG response.
      The diagnosis of acute myelogenous leukemia and age group were 2 independent
      patient factors associated with significantly reduced cellular immune responses
      to JCV. This prospective study in HSCT patients provides a model of interactions
      between the host immune response and viral activation in multiple compartments
      during the recovery of the immune system.

PMID- 24680977
TI  - Janus kinase inhibitors and allogeneic stem cell transplantation for
      myelofibrosis.
AB  - Myelofibrosis (MF) is a manifestation of several disorders of hematopoiesis,
      collectively referred to as myeloproliferative neoplasms. Allogeneic
      hematopoietic stem cell transplantation (ASCT) is the only therapy with proven
      curative potential. However, most patients with MF are in their 6th or 7th decade
      of life, and only some of these patients have been considered suitable
      transplantation candidates. The development of reduced-intensity conditioning
      regimens with limited toxicity has allowed clinicians to offer ASCT to a growing
      number of older patients. The availability of Janus Kinase (JAK) 1/2 inhibitors
      allows clinicians to provide symptom relief and improved quality of life for MF
      patients. These drugs may also affect the decision regarding, in particular, the
      timing of ASCT. Future studies need to address the role of JAK1/2 inhibitors in
      patients who are transplantation candidates and determine their role before and,
      possibly, after transplantation. The identification of indications for the use of
      JAK1/2 inhibitors in the context of transplantation may lead to new therapeutic
      strategies for patients with MF. 

PMID- 24680978
TI  - Polymorphism of CD44 influences the efficacy of CD34(+) cells mobilization in
      patients with hematological malignancies.
AB  - In the last decade, peripheral blood was the main source of hematopoietic stem
      cells (HSC) for autologous and allogeneic transplantation. The exact mechanisms
      of HSC mobilization are still not clear and the efficacy of the procedure is
      hardly predictable. Ligand-receptor interactions of adhesion molecules, such as
      SDF1/CXCR4, VLA4/VCAM-1, or CD44/osteopontin, play an important role in homing of
      HSC in the hematopoietic niche. There is some evidence that disruption of the
      ligand-receptor complex leads to the egress of HSCs to the peripheral blood. The
      aim of the present study was the evaluation of constitutive polymorphism of genes
      encoding cytokines and receptors present in the HSC niche and their impact on the
      efficacy of mobilization of HSCs in patients with hematological malignancies. We
      enrolled 110 patients (60 females and 50 males) in the study. The median age of
      the patients was 55 (range, 22 to 69) years. The group consisted of patients with
      multiple myeloma (n = 74), non-Hodgkin lymphoma (n = 19), Hodgkin lymphoma (n =
      15), or acute myeloid leukemia (n = 2). The mobilization procedures comprised
      chemotherapy and subsequent granulocyte-colony stimulating factor (G-CSF) at a
      dose of 10 MUg/kg daily. The poor mobilizers group was defined according to
      Italian National Bone Marrow Transplant Registry criteria: patients with peak
      CD34(+) in the peripheral blood < 20/MUL or total yield < 2 * 10(6) CD34(+)
      cells/kg body weight in maximum 3 aphereses. Genotyping was performed using
      standard PCR-based assays. The group of patients (N = 108) who achieved minimal
      threshold for collections (CD34(+) at least 10/MUL) proceeded to apheresis. The
      median total yield of CD34(+) in this group was 5.6 * 10(6) cells/kg body weight,
      whereas the median number of cells collected during the first apheresis was 3.3 *
      10(6) cells/kg body weight. Median number of days of G-CSF treatment before first
      apheresis was 10. Fifteen patients fulfilled the criteria for poor mobilizer. The
      group of poor mobilizers had higher frequency of TT genotype in rs13347 (CD44)
      gene (CC+ CT versus TT P = .047). Patients homozygous for T allele had a lower
      total yield of CD34(+) cells/kg body weight than the group with allele C (median,
      3.7 * 10(6)/kg versus 5.8 * 10(6)/kg; P = .019) and a lower number of CD34(+)
      cells gathered during first apheresis (.95 * 10(6)/kg versus 3.3 * 10(6)/kg, P =
      .04). Multivariate logistic regression analysis revealed that the CD44 TT
      genotype was the only factor associated with 5-fold higher risk of poor
      mobilization (P = .037). Polymorphic variants of CXCR4 and VCAM-1 did not
      significantly influence the efficacy of HSCs mobilization in our group of
      patients. In conclusion, our results indicate that among investigated single
      nucleotide polymorphisms (SNPs), only CD44 rs13347 has an impact on the efficacy
      of HSCs mobilization in patients with hematologic malignancies. CD44 SNPs
      analysis may be helpful for predicting the poor mobilizers population who may
      benefit from newer modalities using adhesion molecules inhibitors.

PMID- 24680979
TI  - Expression of protein gene product 9.5 and Sal-like protein 4 in canine
      seminomas.
AB  - The aim of the present study was to characterize canine classical seminoma (SE)
      and spermatocytic seminoma (SS) by immunohistochemical expression of gonocytic
      and spermatogonial cellular markers (c-Kit, placental alkaline phosphatase
      [PLAP], protein gene product 9.5 [PGP9.5] and Sal-like protein 4 [Sall4]) and
      histochemically by the periodic acid-Schiff (PAS) reaction. Twenty-five cases of
      SE and 23 cases of SS were investigated. Two cases of dysgerminoma were also
      examined. c-Kit was expressed on the cell membrane of 13 of 25 cases of SE (52%)
      and four of 23 cases of SS (16%). This marker was not expressed in dysgerminoma.
      PLAP immunoreactivity was observed in the cytoplasm of neoplastic cells of six of
      25 cases of SE (24%). PLAP was not expressed in cases of SS and dysgerminoma. All
      samples of SE, SS and dysgerminoma showed cytoplasmic expression of PGP9.5 and
      nuclear immunoreactivity for Sall4. There was fine granular cytoplasmic PAS
      staining in neoplastic cells in five of 25 cases of SE (20%), while all samples
      of SS and dysgerminoma cases were PAS negative. These findings suggest that it is
      not possible to differentiate canine SE and SS using these markers. This may be
      because canine SS may be derived from spermatogonia that can differentiate to
      spermatocytes and also because cases of canine SE might consist of neoplastic
      cells that have lost their gonocytic nature. This study was the first to show
      positive immunoreactivity for Sall4 in canine seminomas and dysgerminomas and
      expression of PGP9.5 in canine dysgerminomas. 

PMID- 24680980
TI  - Atmospheric concentrations of persistent organic pollutants over the Pacific
      Ocean near southern Taiwan and the northern Philippines.
AB  - This study investigates the atmospheric occurrence of persistent organic
      pollutants (POPs) over the Pacific Ocean near southern Taiwan and the northern
      Philippines. We determined sixty-six compounds, including polychlorinated dibenzo
      p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls
      (DLPCBs), polybrominated diphenyl ethers (PBDEs), as well as polychlorinated
      diphenyl ethers (PCDEs), polybrominated dibenzo-p-dioxins and dibenzofurans
      (PBDD/Fs), and polybrominated biphenyls (PBBs), in air samples simultaneously
      collected from the offshore oceanic atmosphere (n=6) and over a rural area (n=2).
      We calculated the atmospheric World Health Organization 2005 toxic equivalency
      levels (WHO2005-TEQ), for the total dioxin-like POPs, including PCDD/Fs, DLPCBs,
      and PBDD/Fs, being 0.00612 pg WHO2005-TEQ/m(3) and 0.0138 pg WHO2005-TEQ/m(3)
      over the ocean and land, respectively. We found unexpected lower averaged
      atmospheric PBDE concentrations in the rural area (15.9 pg/m(3)) than over the
      ocean (31.1 pg/m(3)) due to higher levels of the BDE209 congener, although the
      difference was not statistically significant. We have compared and reported our
      field results with previously published datasets over the global oceans, which
      suggest PCBs and PBDEs are the dominant chemical contaminants in the global
      oceanic atmosphere among these halogenated POPs (e.g. PCBs and Sigmadi-hepta
      PBDEs could be found in the range of 0.09-48.7 and 8.07-94.0 pg/m(3),
      respectively, including our dataset). However, there are still very few
      investigations on the global atmospheric levels of PBDD/Fs, PCDEs and PBBs and
      our data sums to these earlier studies. Finally, we point out that the
      halogenated POPs originated from Taiwan or the continental East Asia which could
      easily reach remote ocean sites via atmospheric transport.

PMID- 24680981
TI  - A comparative study of the aneugenic and polyploidy-inducing effects of fisetin
      and two model Aurora kinase inhibitors.
AB  - Fisetin, a plant flavonol commonly found in fruits, nuts and vegetables, is
      frequently added to nutritional supplements due to its reported cardioprotective,
      anti-carcinogenic and antioxidant properties. Earlier reports from our laboratory
      and others have indicated that fisetin has both aneugenic and clastogenic
      properties in cultured cells. More recently, fisetin has also been reported to
      target Aurora B kinase, a Ser/Thr kinase involved in ensuring proper microtubule
      attachment at the spindle assembly checkpoint, and an enzyme that is
      overexpressed in several types of cancer. Here we have further characterized the
      chromosome damage caused by fisetin and compared it with that induced by two
      known Aurora kinase inhibitors, VX-680 and ZM-447439, in cultured TK6 cells using
      the micronucleus assay with CREST staining as well as a flow cytometry-based
      assay that measures multiple types of numerical chromosomal aberrations. The
      three compounds were highly effective in inducing aneuploidy and polyploidy as
      evidenced by increases in kinetochore-positive micronuclei, hyperdiploidy, and
      polyploidy. With fisetin, however, the latter two effects were most significantly
      observed only after cells were allowed to overcome a cell cycle delay, and
      occurred at higher concentrations than those induced by the other Aurora kinase
      inhibitors. Modest increases in kinetochore-negative micronuclei were also seen
      with the model Aurora kinase inhibitors. These results indicate that fisetin
      induces multiple types of chromosome abnormalities in human cells, and indicate a
      need for a thorough investigation of fisetin-augmented dietary supplements.

PMID- 24680982
TI  - Plasma proprotein convertase subtilisin-kexin type 9 is predominantly related to
      intermediate density lipoproteins.
AB  - OBJECTIVES: Proprotein convertase subtilisin-kexin type 9 (PCSK9) is a key
      regulator of low density lipoprotein (LDL) receptor processing, but the PCSK9
      pathway may also be implicated in the metabolism of triglyceride-rich
      lipoproteins. Here we determined the relationship of plasma PCSK9 with very low
      density lipoprotein (VLDL) and LDL subfractions. DESIGN AND METHODS: The
      relationship of plasma PCSK9 (sandwich enzyme-linked immunosorbent assay) with 3
      very low density lipoprotein (VLDL) and 3 low density lipoprotein (LDL)
      subfractions (nuclear magnetic resonance spectroscopy) was determined in 52
      subjects (30 women). RESULTS: In age- and sex-adjusted analysis plasma PCSK9 was
      correlated positively with total cholesterol, non-high density lipoprotein
      cholesterol and LDL cholesterol (r=0.516 to 0.547, all p<0.001), as well as with
      triglycerides (r=0.286, p=0.044). PCSK9 was correlated with the VLDL particle
      concentration (r=0.336, p=0.017) and with the LDL particle concentration
      (r=0.362, p=0.010), but only the relationship with the LDL particle concentration
      remained significant in multivariable linear regression analysis. In an analysis
      which included the 3 LDL subfractions, PCSK9 was independently related to
      intermediate density lipoproteins (IDL) (p<0.001), but not to other LDL
      subfractions. CONCLUSIONS: This study suggests that plasma PCSK9 predominantly
      relates to IDL, a triglyceride-rich LDL subfraction. The PCSK9 pathway may affect
      plasma triglycerides via effects on the metabolism of triglyceride-rich LDL
      particles.

PMID- 24680983
TI  - Using large clinical corpora for query expansion in text-based cohort
      identification.
AB  - In light of the heightened problems of polysemy, synonymy, and hyponymy in
      clinical text, we hypothesize that patient cohort identification can be improved
      by using a large, in-domain clinical corpus for query expansion. We evaluate the
      utility of four auxiliary collections for the Text REtrieval Conference task of
      IR-based cohort retrieval, considering the effects of collection size, the
      inherent difficulty of a query, and the interaction between the collections. Each
      collection was applied to aid in cohort retrieval from the Pittsburgh NLP
      Repository by using a mixture of relevance models. Measured by mean average
      precision, performance using any auxiliary resource (MAP=0.386 and above) is
      shown to improve over the baseline query likelihood model (MAP=0.373).
      Considering subsets of the Mayo Clinic collection, we found that after including
      2.5 billion term instances, retrieval is not improved by adding more instances.
      However, adding the Mayo Clinic collection did improve performance significantly
      over any existing setup, with a system using all four auxiliary collections
      obtaining the best results (MAP=0.4223). Because optimal results in the mixture
      of relevance models would require selective sampling of the collections, the
      common sense approach of "use all available data" is inappropriate. However, we
      found that it was still beneficial to add the Mayo corpus to any mixture of
      relevance models. On the task of IR-based cohort identification, query expansion
      with the Mayo Clinic corpus resulted in consistent and significant improvements.
      As such, any IR query expansion with access to a large clinical corpus could
      benefit from the additional resource. Additionally, we have shown that more data
      is not necessarily better, implying that there is value in collection curation. 

PMID- 24680984
TI  - Formalizing MedDRA to support semantic reasoning on adverse drug reaction terms.
AB  - Although MedDRA has obvious advantages over previous terminologies for coding
      adverse drug reactions and discovering potential signals using data mining
      techniques, its terminological organization constrains users to search terms
      according to predefined categories. Adding formal definitions to MedDRA would
      allow retrieval of terms according to a case definition that may correspond to
      novel categories that are not currently available in the terminology. To achieve
      semantic reasoning with MedDRA, we have associated formal definitions to MedDRA
      terms in an OWL file named OntoADR that is the result of our first step for
      providing an "ontologized" version of MedDRA. MedDRA five-levels original
      hierarchy was converted into a subsumption tree and formal definitions of MedDRA
      terms were designed using several methods: mappings to SNOMED-CT, semi-automatic
      definition algorithms or a fully manual way. This article presents the main steps
      of OntoADR conception process, its structure and content, and discusses problems
      and limits raised by this attempt to "ontologize" MedDRA. 

PMID- 24680985
TI  - The long road to semantic interoperability in support of public health:
      experiences from two states.
AB  - Proliferation of health information technologies creates opportunities to improve
      clinical and public health, including high quality, safer care and lower costs.
      To maximize such potential benefits, health information technologies must readily
      and reliably exchange information with other systems. However, evidence from
      public health surveillance programs in two states suggests that operational
      clinical information systems often fail to use available standards, a barrier to
      semantic interoperability. Furthermore, analysis of existing policies
      incentivizing semantic interoperability suggests they have limited impact and are
      fragmented. In this essay, we discuss three approaches for increasing semantic
      interoperability to support national goals for using health information
      technologies. A clear, comprehensive strategy requiring collaborative efforts by
      clinical and public health stakeholders is suggested as a guide for the long road
      towards better population health data and outcomes. 

PMID- 24680987
TI  - Cranial neural crest: migratory cell behavior and regulatory networks.
AB  - Defects of the head and neck region account for a substantial portion of all
      human birth disorders. The high incidence of malformations in this region may be
      attributed in part to the intricate means by which the facial region is assembled
      during embryonic development. The starting constituent for the majority of
      skeletal and connective tissues in the face is a pluripotent population of cells,
      the cranial neural crest (CNC) cells. This population of cells exhibit remarkable
      migratory abilities and diversity of potential cell types. This review draws on
      extensive research that has been done in the field, focusing specifically on
      findings generated in the last decade on cell behavior and the gene regulatory
      networks of migratory CNC cells. In the later part of this review, the importance
      of the CNC cells in the overall development of the craniofacial region will be
      illustrated with a discussion of a craniofacial birth defect, the Treacher
      Collins syndrome. The next decade will most likely herald in an era of greater
      understanding of the integrative molecular networks at different stages of the
      development of the CNC cells. Such new information is essential towards a better
      understanding the etiology and pathogenesis of the many craniofacial birth
      defects and will ultimately lead to new therapeutic modalities. 

PMID- 24680986
TI  - Pathophysiology and spectrum of diseases caused by defects in lymphocyte
      cytotoxicity.
AB  - In experimental settings, lymphocyte cytotoxicity has been recognized as a
      central mechanism for immune defense against infected and neoplastic cells. More
      recently, molecular determinants of lymphocyte cytotoxicity have been identified
      through studies of rare, inherited hyperinflammatory and lymphoproliferative
      syndromes that include hemophagocytic lymphohistiocytosis (HLH). These studies
      have unraveled a set of genes pivotal for the biogenesis and directed release of
      perforin-containing lysosomes that mediate target cell killing, in addition to
      other pathways including Fas that also contribute to induction of cell death.
      Furthermore, studies of such human primary immunodeficiencies have highlighted
      non-redundant roles of perforin for maintenance of immune homeostasis. Besides
      providing mechanistic insights to lymphocyte cytotoxicity, studies of individuals
      with rare hyperinflammatory diseases are highlighting the relevance of lymphocyte
      cytotoxicity to more common human diseases. It is increasingly recognized that
      mutations abrogating lymphocyte cytotoxicity not only cause HLH, but also are
      associated with susceptibility to cancer and autoimmune syndromes. In addition,
      patients may initially be present with neurological symptoms or severe infectious
      disease masquerading as variable immunodeficiency syndrome. Here, we highlight
      new knowledge regarding the molecular mechanisms regulating lymphocyte
      cytotoxicity and review how mutations in genes associated with HLH cause disease.
      We also discuss the wider implications of impairments in lymphocyte cytotoxicity
      for human disease predisposition. 

PMID- 24680988
TI  - No role for vitamin D or a moderate fat diet in aging induced cognitive decline
      and emotional reactivity in C57BL/6 mice.
AB  - BACKGROUND: Epidemiological studies have shown associations between vitamin D,
      mental health and glucose homeostasis in the elderly. Causal evidence, however,
      is still lacking. OBJECTIVE: The objective of this study was to investigate the
      importance of vitamin D in the prevention of emotional disturbances and cognitive
      decline in aging C57BL/6 mice, with pre-diabetes type II as potential effect
      modifier. METHODS: Mice were exposed to one of four diets from 10 months till 24
      months of age: low fat vitamin D adequate (LFD), LF vitamin D deficient (LF),
      moderate fat vitamin D adequate (MFD), and MF vitamin D deficient (MF). The
      MFD/MF diet was applied to induce a condition resembling pre-diabetes type II.
      Behavior was assessed twice in the same group of mice at 6-8 and at 22-23 months
      of age using the Open Field Test (OFT), Elevated Plus Maze (EPM), Object
      Recognition Test (ORT) and the Morris Water Maze (MWM). RESULTS: We successfully
      induced vitamin D deficiency in the LF/MF mice. Moreover, fasting glucose and
      fasting insulin levels were significantly higher in MFD/MF mice than in LFD/LF
      mice. A significant aging effect was observed for most behavioral parameters. A
      MF(D) diet was shown to delay or prevent the age-related increase in emotional
      reactivity in the EPM. No effect of vitamin D or vitamin D*fat on behavioral
      outcomes was measured. CONCLUSION: Aging significantly affected emotional
      reactivity and cognitive performance. Although other studies have shown effects
      of vitamin D on emotional reactivity and cognitive performance in mice, these
      findings could not be confirmed in aged C57BL/6 mice in this study.

PMID- 24680989
TI  - Documentation and quantitative analysis of local ethnozoological knowledge among
      traditional healers of Theni district, Tamil Nadu, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study investigated the use of animals among
      the traditional healers in Theni district of Tamil Nadu, India. The data
      regarding the medicinal animals/animal products were documented and their usages
      were analyzed quantitatively. MATERIALS AND METHODS: Based on free list
      interviews with the traditional healers, we documented the medicinal usage of
      animals/animal products and calculated the indices such as informant consensus
      factor (Fic) to determine the consensus over the species for an illness category,
      as well as the Index Agreement on Remedies (IAR) to determine the extent of
      potential utilization of each species. RESULTS: In this study, 69 medicinal
      animals/animal products were documented with the help of standardized
      questionnaires among the local healers. The results were tabulated and Fic value
      for each illness category was calculated. Three illness categories viz., jaundice
      (milk of Capra aegagrus hircus), orthopedics (egg white and meat of Gallus gallus
      domesticus) and pediatrics (milk of Equus africanus asinus) had got high Fic
      values. Fifteen illness categories had moderate Fic values. Highly cited animals
      in these illness categories were: Rusa unicolor (antiemetic), Reticulitermes spp.
      (diabetes), flesh of Varanus benghalensis (oral ailments), milk (eye ailments,
      fever) and urine (antidote) of Homo sepians, meat of Trachypithecus johnii
      (respiratory ailments), various parts of C. aegagrus hircus (blood ailments,
      coolants, diarrhea, pulmonary and urinary ailments), flesh of Chamaeleon
      zeyalnica (neural ailments), meat of Passer domesticus (aphrodisiac), curd and
      dung of Bos primigenius taurus (dermatological ailments), meat of G. domesticus
      (musculo-skeletal disorders, analgesic), meat of Lissemys punctata (hemorrhoids),
      and Pherthima posthuma (psychological ailments). Six illness categories had low
      Fic values. CONCLUSION: This study indicated that the animals are still being
      used by the local healers of Theni district, to treat various illnesses. Cross
      disciplinary approaches to explore the full potential of animal-derived medicines
      will help to improve the health of local people.

PMID- 24680990
TI  - Chemical composition and antinociceptive effect of aqueous extract from Rourea
      induta Planch. leaves in acute and chronic pain models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rourea induta Planch. is a small tree or shrub
      growing wild in Brazil and belonging to the Connaraceae family. It is used for
      the treatment of Chagas disease and as antirheumatic in folk medicine. This study
      was designed to investigate the antinociceptive activity of the aqueous extract
      (AERi) of Rourea induta leaves in rodents, as well as isolate and identify
      components that can be responsible for its effect. MATERIAL AND METHODS: The
      antinociceptive effect of orally administered AERi was evaluated in behavioral
      models of acute (formalin) and chronic [complete Freund's adjuvant (CFA)] pain in
      mice. We also investigated the possible involvement of opioid receptors and
      proinflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha) in
      the antinociceptive effect of the AERi. In addition, a nonspecific effect of AERi
      was evaluated by measuring locomotor activity and corporal temperature. Finally,
      we performed a phytochemical analysis of AERi. RESULTS: HPLC titration revealed
      the presence of hyperin (21.6 mg/g), quercetin-3-O-beta-xyloside (4.4 mg/g),
      quercetin-3-O-alpha-arabinofuranoside (12.0 mg/g), and quercetin (2.1 mg/g). It
      was also possible to isolate minor constituents' chlorogenic acid, neochlorogenic
      acid and procyanidin C1. The oral administration of AERi (100 mg/kg)
      significantly inhibited the neurogenic (37 +/- 5%) and inflammatory (34 +/- 7%)
      phases of formalin-induced pain. Acute and repeated treatment of animals with
      AERi (100 mg/kg, p.o.) once a day markedly reduced the mechanical
      hypersensitivity response induced by CFA, and this effect was evident until the
      day 10. Moreover, repeated treatment with AERi (100 mg/kg, p.o.) significantly
      reduced the levels of IL-1beta and TNF-alpha in the paw (22 +/- 7% and 50 +/-
      19%) and in the spinal cord (100% and 100%) when compared to the CFA group. The
      AERi (100 mg/kg, p.o.) markedly reduced biting behavior induced by intrathecal
      injection of TNF-alpha (81 +/- 11%). Finally, the effect of AERi was not
      associated with changes in locomotor activity or the corporal temperature of
      animals. CONCLUSION: These data show that aqueous extract of Rourea induta has
      significant antinociceptive action, which seems to be associated with an
      inhibition of pro-inflammatory cytokines activated pathways. These findings
      support the ethnomedical uses of this plant.

PMID- 24680991
TI  - Phytotherapy of Polish migrants in Misiones, Argentina: legacy and acquired plant
      species.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Analyzing how and why phytotherapeutical
      practices survive a migratory process is important for understanding migrant
      health seeking behaviour and health demand. Contrary to most studies, which focus
      on migrants from warm climates who settle in European and American cities, this
      study explores continuations in the herbal pharmacopoeia of Eastern European
      peasants who settled down in rural subtropical areas of Argentina. The study also
      explores the pharmacopoeia among the descendants of the first generation born in
      Argentina. MATERIAL AND METHODS: Primary and secondary sources were employed in
      the study. Data were collected during over 200 interviews (semi-structured, free
      lists and in-depth) with 94 study participants. Voucher specimens of species
      mentioned were gathered and identified. Illnesses were reported according to
      local ethnomedical terminology and classification. Only reports from informants'
      own experience were included in the analysis. The unit of analysis was a plant
      use report (plant species * plant part * ailment * informant). The frequency of
      mentions was calculated for plant parts used and modes of preparation and
      administration of herbal medicines, and the Informant Diversity Value was also
      estimated. Secondary information was obtained from ethnobotanical and
      ethnomedical literature concerning the whole of Poland. A list was made of
      medicinal plant species known from Poland available in the study area. Then, the
      similarity between the available species and those used by Polish migrants was
      evaluated by applying the Simpson index. RESULTS: An exhaustive list of 129 plant
      species used by the Polish community in Misiones, Argentina, was obtained. Among
      37 species known form Poland and available in Misiones, 19 were used by the
      community. There was low consensus on the treatment of health conditions with
      legacy plants between Polish migrants and the Polish folk pharmacopoeia. The
      reasons for the relatively low use of legacy species are explained. More
      continuation has been observed in forms of application and administration of
      medicinal plants. Most of the continued species are food plants and are
      predominantly applied as medicinal food. CONCLUSIONS: In the migratory process,
      Polish peasants have preserved culturally salient species, which have a wide
      range of therapeutic applications and are easily accessible. Polish migrants and
      their descendants have incorporated a great number of local medicinal plant
      species into their home medicine but at the same time retained traditional ways
      of administration of herbal medicines. Based on the theory of acculturation, the
      observed patterns of medicinal plant use in Polish migrant colonies in Misiones
      indicate good adaptation to the predominant cultural environment.

PMID- 24680992
TI  - In vitro effects of active components of Polygonum Multiflorum Radix on enzymes
      involved in the lipid metabolism.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Raw and processed Polygoni Multiflori Radix (PMR and
      PMRP) are used in the prevention and treatment of non-alcoholic fatty liver
      disease (NAFLD), hyperlipidemia or related diseases. In our previous research, 2,
      3, 5, 4'-tetrahydroxy-stilbene-2-O-beta-D-glucoside (TSG) displayed the most
      important role in the total cholesterol (TC) lowering effect among all the
      chemical constituents of Polygonum multiflorum. Emodin and physcion displayed
      more favorable triglyceride (TG) reducing effects than TSG. However, there are
      few researches focus on the approach and mechanism of how do Polygonum
      multiflorum exhibit good lipid regulation activity. The targeted sites of active
      substances of Polygonum multiflorum are still not clearly elucidated. This
      research pays close attention to how major chemical components of Polygonum
      multiflorum affect the TC and TG contents in liver cells. MATERIALS AND METHODS:
      In this research, a sensitive, accurate and rapid in vitro model, steatosis
      hepatic L02 cell, was used to explore target sites of active chemical substances
      of Polygonum multiflorum for 48h. Steatosis hepatic L02 cell was exposed to
      emodin, physcion and TSG, respectively. The contents of four key enzymes in the
      pathway of synthesis and decomposition of TC and TG were investigated after
      exposure. Meanwhile, the contents of lipid transfer protein were also tested. The
      diacylgycerol acyltransferase 1 (DGAT1) controlled the biosynthesis of TG from
      free fatty acids while 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA
      reductase) limited the biosynthesis of TC. Hepatic triglyceride lipase (HTGL) and
      cholesterol 7alpha-hydroxylase (CYP7A) played the key role in the lipolysis
      procedure of TG and TC. RESULTS: The synthesis of TC and TG in steatosis L02
      cells were apparently increased in the model group compared to the control group.
      Intracellular contents of HMG-CoA reductase and DGAT1 increased 32.33% and
      56.52%, while contents of CYP7A and HTGL decreased 21.61% and 47.37%. Emodin,
      physcion and TSG all showed down-regulation effects on HMG-CoA reductase, while
      up-regulation effects on CYP7A. The most remarkable effect on HMG-CoA reductase
      was found on emodin. Emodin could reduce the DGAT1 content from 438.44 +/- 4.51
      pg/mL in model group to 192.55 +/- 9.85 pg/mL (100 MUm). The content of HTGL in
      300 MUm physcion group was 3.15 +/- 0.15 U/mL, which was more significantly
      effective than the control, lovastatin and fenofibrate group. CONCLUSIONS: TSG
      could raise the content of CYP7A and then promote the lipolysis of cholesterol.
      Moreover, TSG also showed the best LDL-reducing effect. Emodin could inhibit HMG
      CoA reductase and DGAT1, which were key enzymes in the synthesis of TC and TG.
      Physcion increased the content of HTGL, and then could boost the lipolysis of
      triglyceride. At the same time, physcion showed the best VLDL-reducing effect. In
      view of the above conclusions, we contributed the lipid regulation activity to an
      overall synergy of TSG, emodin and physcion.

PMID- 24680993
TI  - Antiarrhythmic effects of dehydroevodiamine in isolated human myocardium and
      cardiomyocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dehydroevodiamine alkaloid (DeHE), a bioactive
      component of the Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), exerted
      antiarrhythmic effect in guinea-pig ventricular myocytes. We further characterize
      the electromechanical effects of DeHE in the human atrial and ventricular tissues
      obtained from hearts of patients undergoing corrective cardiac surgery or heart
      transplantation. MATERIALS AND METHODS: The transmembrane potentials of human
      myocardia were recorded with a traditional microelectrode technique while
      sarcolemmal Na(+) and Ca(2+) currents in single human cardiomyocytes were
      measured by a whole-cell patch-clamp technique. The intracellular pH (pHi) and
      Na(+)-H(+) exchanger (NHE) activity were determined using BCECF-fluorescence in
      human atria. RESULTS: In human atria, DeHE (0.1-0.3 MUM) depressed upstroke
      velocity, amplitude of action potential, and contractile force, both in slow and
      fast response action potential. Moreover, the similar depressant effects of DeHE
      were found in human ventricular myocardium. Both in isolated human atrial and
      ventricular myocytes, DeHE (0.1-1 MUM) reversibly, concentration-dependently
      decreased the Na(+) and Ca(2+)currents. Moreover, DeHE (0.1 and 0.3 MUM)
      suppressed delayed afterdepolarizations and aftercontractions, induced by
      epinephrine and high [Ca(2+)]o in atria. In human ventricular myocardium, the
      strophanthidin-induced triggered activities were attenuated by pretreating DeHE
      (0.3 MUM). The resting pHi and NHE activity were also significantly increased by
      DeHE (0.1-0.3 MUM). CONCLUSIONS: We concluded for the first time that, in the
      human hearts, DeHE could antagonize triggered arrhythmias induced by cardiotonic
      agents through a general reduction of the Na(+) and Ca(2+) inward currents, while
      increase of resting pHi and NHE activity.

PMID- 24680994
TI  - Protective effect of Actiniopteris radiata (Sw.) Link. against CCl4 induced
      oxidative stress in albino rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Actiniopteris radiata is a herb with great
      medicinal value and is evaluated for hepatoprotective activity. To investigate
      the protective effect of ethanolic extract of Actiniopteris radiata (EEAR) on
      CCl4 induced oxidative stress in male Wistar albino rats. MATERIALS AND METHODS:
      EEAR were administered for 8 consecutive weeks to rats. Group I - control; Group
      II - toxin control (30% CCl4); Group III and Group IV received EEAR (250 and 500
      mg/kg respectively). Antioxidant status in liver were estimated by determining
      the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase
      (CAT) and glutathione peroxidase (GPx); as well as by determining the levels of
      lipid peroxidation (LPO) and reduced glutathione (GSH). In addition, isoenzyme
      pattern and mRNA expression of the antioxidants were studied. Partial
      characterization of EEAR was performed by Liquid chromatography-mass spectrometry
      (LC-MS). RESULTS: CCl4 induced oxidative stress as evidenced from increase in LPO
      along with reduction of SOD, CAT, GPx and GSH. Treatment with EEAR (250 and 500
      mg/kg) mitigated the CCl4 induced oxidative stress. An analysis of the isozyme
      pattern of these antioxidant enzymes revealed variations in SOD2, CAT, GPx2 and
      GPx3 in CCl4 treated rats, which were normalized after EEAR treatment.
      Furthermore, expression of genes for the antioxidant enzymes, were down-regulated
      by CCl4 treatment, which were reversed by EEAR. The results of partial
      characterization of EEAR by LC-MS revealed the presence of rutin and other 7
      unknown phenolic derivatives. CONCLUSIONS: These findings suggest the protective
      effect of EEAR against CCl4 induced oxidative stress might be attributed to the
      presence of flavonoids and phenolic compounds.

PMID- 24680995
TI  - Curcumin inhibits microglia inflammation and confers neuroprotection in
      intracerebral hemorrhage.
AB  - Much evidence demonstrates that microglia mediated neuroinflammation is an
      important contributor to the inflammatory injury in intracerebral hemorrhage
      (ICH). Therefore, the compounds that can inhibit neuroinflammation are greatly
      needed. In the current study, we examined whether curcumin, present in a Chinese
      medicinal plant, could prevent ICH induced microglia activation and confer
      protection against neurotoxicity. The cytokines of microglia were measured by
      ELISA, p38MAPK/PKC and NF-kappaB were measured by Western blot and EMSA.
      Microglial toxicity was assessed using MTT and FACS assays. And neurological
      function was evaluated by animal behavioristics. We found that curcumin prevented
      ICH-induced inflammatory molecules through NF-kappaB activation via the
      p38MAPK/PKC pathway in vitro. In addition, curcumin protected hippocampal HT22
      cells from indirect toxicity mediated by ICH-treated microglia cells. Further,
      curcumin also attenuated ICH-induced neurological deficit and cerebral water
      content in vivo. Together, our findings suggest that curcumin could suppress ICH
      induced inflammatory injury and represent a novel herbal sources for ICH
      therapeutical strategy. 

PMID- 24680997
TI  - Editorial comment.

PMID- 24680998
TI  - Editorial comment.

PMID- 24680999
TI  - Meta-analysis of IgE-binding allergen epitopes.
AB  - IgE-binding epitopes are related to allergic symptoms by eliciting degranulation
      of special cells and release of molecules that trigger the hypersensitivity
      reaction. Little is known about what characterises allergen IgE-binding epitopes,
      although advances in analytical methods have led to the identification of a large
      number of them. To assess if a binary classification of allergen regions into
      epitopes or non-epitopes may accurately reflect biological reality, we computed
      the fraction of allergen amino acids that are involved in epitopes. A
      relationship between this fraction and the increasing number of literature
      references was modelled. Due to the wide variety of methods that are used in the
      literature, a peak in the number of matches between an allergen sequence and its
      epitopes confirms their validity. Accordingly, our graphical representation of
      positive assays along sequences provides an overview of epitope localisation,
      which should help to highlight major positions for IgE binding to allergens. 

PMID- 24681000
TI  - The nucleus raphe magnus OFF-cells are involved in diffuse noxious inhibitory
      controls.
AB  - Diffuse noxious inhibitory controls (DNIC) are very powerful long-lasting
      descending inhibitory controls which are pivotal in modulating the activity of
      spinal and trigeminal nociceptive neurons. DNIC are subserved by a loop involving
      supraspinal structures such as the lateral parabrachial nucleus and the
      subnucleus reticularis dorsalis. Surprisingly, though, whether the nucleus raphe
      magnus (NRM), another supraspinal area which is long known to be important in
      pain modulation, is involved in DNIC is still a matter of discussion. Here, we
      reassessed the role of the NRM neurons in DNIC by electrophysiologically
      recording from wide dynamic range (WDR) neurons in the trigeminal subnucleus
      oralis and pharmacologically manipulating the NRM OFF- and ON-cells. In control
      conditions, C-fiber-evoked responses in trigeminal WDR neurons are inhibited by a
      conditioning noxious heat stimulation applied to the hindpaw. We show that
      inactivating the NRM by microinjecting the GABAA receptor agonist, muscimol, both
      facilitates C-fiber-evoked responses of trigeminal WDR neurons and strongly
      attenuates their inhibition by heat applied to the hindpaw. Interestingly,
      selective blockade of ON-cells by microinjecting the broad-spectrum excitatory
      amino acid antagonist, kynurenate, into the NRM neither affects C-fiber-evoked
      responses nor attenuates DNIC of trigeminal WDR neurons. These results indicate
      that the NRM tonically inhibits trigeminal nociceptive inputs and is involved in
      the neuronal network underlying DNIC. Moreover, within NRM, OFF-cells might be
      more specifically involved in both the tonic and phasic descending inhibitory
      controls of trigeminal nociception. 

PMID- 24681001
TI  - Th17 cells in central nervous system autoimmunity.
AB  - Multiple sclerosis (MS) is the most important autoimmune disease of the central
      nervous system (CNS). Its animal model experimental autoimmune encephalomyelitis
      (EAE) has been instrumental in defining the features of the novel T helper cell
      subset Th17. Conversely, the broad characterization of Th17 immune responses has
      substantially advanced our understanding of organ-specific autoimmunity and
      inspired almost a decade of immunological research. Here, we review the current
      knowledge on Th17 cells and their contribution to the immunopathology in EAE and
      MS, covering recent proceedings in the induction, modulation and effector
      mechanisms of this versatile T lymphocyte subset. In particular, we discuss the
      emerging role of mucosal immunity in the regulation of Th17 cells and CNS
      autoimmunity, the accumulating evidence for extensive plasticity in the Th17
      subset, and their molecular mode of action in promoting this debilitating
      disease.

PMID- 24681002
TI  - Rebuilding the nigrostriatal dopamine pathway: 30 years and counting.

PMID- 24681003
TI  - Interdependent epidermal growth factor receptor signalling and trafficking.
AB  - Epidermal growth factor (EGF) receptor (EGFR) signalling regulates diverse
      cellular functions, promoting cell proliferation, differentiation, migration,
      cell growth and survival. EGFR signalling is critical during embryogenesis, in
      particular in epithelial development, and disruption of the EGFR gene results in
      epithelial immaturity and perinatal death. EGFR signalling also functions during
      wound healing responses through accelerating wound re-epithelialisation, inducing
      cell migration, proliferation and angiogenesis. Upregulation of EGFR signalling
      is often observed in carcinomas and has been shown to promote uncontrolled cell
      proliferation and metastasis. Therefore aberrant EGFR signalling is a common
      target for anticancer therapies. Various reports indicate that EGFR signalling
      primarily occurs at the plasma membrane and EGFR degradation following
      endocytosis greatly attenuates signalling. Other studies argue that EGFR
      internalisation is essential for complete activation of downstream signalling
      cascades and that endosomes can serve as signalling platforms. The aim of this
      review is to discuss current understanding of intersection between EGFR
      signalling and trafficking. 

PMID- 24681004
TI  - The glucosyltransferase Xiantuan of the endoplasmic reticulum specifically
      affects E-Cadherin expression and is required for gastrulation movements in
      Drosophila.
AB  - The majority of membrane and secreted proteins, including many developmentally
      important signalling proteins, receptors and adhesion molecules, are
      cotranslationally N-glycosylated in the endoplasmic reticulum. The structure of
      the N-glycan is invariant for all substrates and conserved in eukaryotes.
      Correspondingly, the enzymes are conserved, which successively assemble the
      glycan precursor from activated monosaccharides prior to transfer to nascent
      proteins. Despite the well-defined biochemistry, the physiological and
      developmental role of N-glycosylation and of the responsible enzymes has not been
      much investigated in metazoa. We identified a mutation in the Drosophila gene,
      xiantuan (xit, CG4542), which encodes one of the conserved enzymes involved in
      addition of the terminal glucose residues to the glycan precursor. xit is
      required for timely apical constriction of mesoderm precursor cells and ventral
      furrow formation in early embryogenesis. Furthermore, cell intercalation in the
      lateral epidermis during germband extension is impaired in xit mutants. xit
      affects glycosylation and intracellular distribution of E-Cadherin, albeit not
      the total amount of E-Cadherin protein. As depletion of E-Cadherin by RNAi
      induces a similar cell intercalation defect, E-Cadherin may be the major xit
      target that is functionally relevant for germband extension. 

PMID- 24681005
TI  - MAD 20 alleles of merozoite surface protein-1 (msp-1) are associated with severe
      Plasmodium falciparum malaria in Pakistan.
AB  - BACKGROUND: Various factors determine the outcome of Plasmodium falciparum
      infection such as parasite load, sequestration, adhesion molecules, and immune
      mediators. P. falciparum merozoite surface protein-1 (msp-1) and msp-2 genotypes
      were also found associated with severe disease. We investigated the association
      between msp-1 and msp-2 genotypes in patients with uncomplicated malaria (UM) and
      severe malaria (SM). METHODS: Twenty-two malaria patients with microscopy
      confirmed P. falciparum infection and eight healthy endemic controls were
      selected for analysis. Nested polymerase chain reaction (PCR) was used to
      identify P. falciparum genotypes. The plasma concentration of cytokines [tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interferon-gamma
      (IFN-gamma)] and chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10]
      were evaluated using enzyme-linked immunosorbent assay (ELISA). RESULTS: TNF
      alpha levels were significantly higher in both UM (389 pg/mL, p = 0.020) and SM
      (771 pg/mL, p = 0.004) compared with healthy controls, while they were greater in
      SM (p = 0.012) as compared to UM. CXCL9 levels were significantly raised in SM as
      compared to UM and negative controls (NCs). CXCL10 levels were raised in UM (550
      pg/mL, p = 0.001) and SM (1480 pg/mL, p = 0.01) as compared with NCs. Increased
      levels of IL-6 were found in patients carrying the FC27 allelic type of msp-2. A
      higher prevalence of MAD 20 and K1 msp-1 alleles was observed in the SM group
      compared to UM. CONCLUSION: Overall, a greater prevalence of MAD 20 alleles and
      increased serum TNF-alpha and CXCL9 levels were associated with severe outcome in
      malaria. Understanding the diversity of malaria genotypes is important for
      predicting disease-related outcomes of P. falciparum infection in endemic areas.

PMID- 24681006
TI  - Brain systems underlying the affective and social monitoring of actions: an
      integrative review.
AB  - Action monitoring allows the swift detection of conflicts, errors, and the rapid
      evaluation of outcomes. These processes are crucial for learning, adaptive
      behavior, and for the regulation of cognitive control. Our review discusses
      neuroimaging and electrophysiological studies that have explored the contribution
      of emotional and social factors during action monitoring. Meta-analytic brain
      activation maps demonstrate reliable overlap of error monitoring, emotional, and
      social processes in the dorsal mediofrontal cortex (dMFC), lateral prefrontal
      areas, and anterior insula (AI). Cumulating evidence suggests that action
      monitoring is modulated by trait anxiety and negative affect, and that activity
      of the dMFC and the amygdala during action monitoring might contribute to the
      'affective tagging' of actions along a valence dimension. The role of AI in
      action monitoring may be the integration of outcome information with self-agency
      and social context factors, thereby generating more complex situation-specific
      and conscious emotional feeling states. Our review suggests that action
      monitoring processes operate at multiple levels in the human brain, and are
      shaped by dynamic interactions with affective and social processes.

PMID- 24681007
TI  - Expanding role of SK channels in cardiac electrophysiology.
AB  - The small conductance calcium-activated potassium (SK) channels are an important
      group of potassium-selective ion channels. SK channels display more pronounced
      expression in the atrium relative to the ventricle. Current evidence relating to
      the functional role of SK channels in the atria is conflicting and whether these
      channels contribute to atrial repolarization under physiological circumstances is
      a matter of debate. Multiple studies have, however, reported that SK channels are
      important mediators of proarrhythmogenic electrical remodeling in the atria. In
      keeping with their expression profile, SK channels do not appear to play a
      prominent role in ventricular repolarization. SK channels represent potentially
      attractive therapeutic targets for atrial fibrillation. A number of
      pharmacological modulators of SK channels have been tested in animal models of
      atrial fibrillation. However, these studies have also demonstrated inconsistent
      results and have raised important questions regarding the proarrhythmogenic
      potential of SK channel modulation. These findings have important implications
      for drug development. This review summarizes the role of SK channels in cardiac
      electrophysiology and discusses the potential role of these channels as
      therapeutic targets. 

PMID- 24681008
TI  - Remote ischemic preconditioning reduces peri-procedural myocardial injury in
      elective percutaneous coronary intervention: a meta-analysis.

PMID- 24681009
TI  - Transient ischemic attack due to an atrial septal defect.

PMID- 24681010
TI  - "Nipple" and "hawk's beak" appearances on contrast left ventricular angiography
      in Takotsubo syndrome: what's in a sign?

PMID- 24681011
TI  - Spontaneous coronary artery dissection following a preeclampsia pregnancy.

PMID- 24681012
TI  - Radiotherapy and prevention of thrombosis in a patient with atrial fibrillation.

PMID- 24681013
TI  - Trends in acute myocardial infarction incidence and relative outcomes on a
      certain insular Mediterranean population.

PMID- 24681014
TI  - Cardiovascular risk markers in dilated cardiomyopathy in Emery-Dreifuss muscular
      dystrophy (EDMD).

PMID- 24681015
TI  - Still a (valuable) place for the pulmonary artery catheter.

PMID- 24681016
TI  - Growth differentiation factor-15 in Takotsubo cardiomyopathy: diagnostic and
      prognostic value.
AB  - BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress responsive
      cytokine, has emerged as a marker of adverse outcome in various cardiovascular
      diseases. Since GDF-15 has not been evaluated in patients with Takotsubo
      cardiomyopathy (TTC), the present study sought to investigate the diagnostic and
      prognostic value in this patient cohort. METHODS: A total of 22 patients
      presenting with TTC were matched for age and gender with 22 ST-segment elevation
      myocardial infarction (STEMI) patients. GDF-15 concentrations were measured at
      admission and 1 day thereafter. The primary clinical endpoint of the TTC cohort
      was the composite of death, cardiogenic shock, or new congestive heart failure
      within 6 months. RESULTS: TTC patients showed significantly higher GDF-15 values
      on admission compared to patients presenting with STEMI (median 3047 ng/l
      [interquartile range 2256-7572] versus median 1527 ng/l [interquartile range 1152
      2677]; p=0.002). TTC patients with a biventricular ballooning pattern and
      patients experiencing major adverse cardiac events during the first 6 months
      after acute presentation showed significantly higher GDF-15 concentrations on
      admission (p=0.008 and p=0.005, respectively). Biventricular ballooning was
      identified as a predictor for elevated GDF-15 values on admission (p=0.03). High
      GDF-15 levels on admission were the only significant predictor for the combined
      clinical endpoint in multivariable regression analysis (p=0.02). CONCLUSION: TTC
      patients showed markedly high, but transient elevation of GDF-15 levels.
      Biventricular ballooning was associated with particularly high GDF-15
      concentrations. Elevated GDF-15 values on admission were a strong predictor of
      adverse clinical outcome.

PMID- 24681017
TI  - Improvement of albuminuria after renal denervation.
AB  - OBJECTIVES: The primary objective of this study was the effect of renal
      denervation (RDN) on elevated urinary albumin-to-creatinine ratio (UACR) in
      treatment-resistant hypertensive patients. In addition, patients were stratified
      according their UACR at baseline into micro- (30-300 mg/g, n=37) and
      macroalbuminuria (>= 300 mg/g, <2,200 mg/g, n=22). BACKGROUND: Increased
      albuminuria indicates cardiovascular and renal damage in hypertension. RDN
      emerged as an innovative interventional approach to reduce blood pressure (BP)
      and may thus reduce albumin urinary excretion. METHODS: Fifty-nine treatment
      resistant hypertensive patients with elevated UACR at baseline underwent catheter
      based RDN using the Symplicity FlexTM catheter (Medtronic Inc., Santa Rosa, CA).
      RESULTS: In the whole and pre-specified subgroups both office and 24-h ambulatory
      BP were significantly reduced 6 months after RDN. In parallel, a significant
      reduction in UACR occurred in all patients (160 (65-496) versus 89 (29-319) mg/g
      creatinine, p<0.001) and in both subgroups (microalbuminuria: 83 (49-153) versus
      58 (17-113) mg/g creatinine, p=0.001; macroalbuminuria: (536 (434-1483) versus
      478 (109-1080) mg/g creatinine, p<0.001). In accordance, the prevalence of micro-
      and macroalbuminuria decreased significantly. Regression analysis revealed a
      modest positive relationship between the decrease of UACR and the fall of
      systolic BP (beta=0.340, p=0.039) independent of renal function. Renal function
      remained unchanged after RDN. CONCLUSIONS: In summary, following RDN, the
      magnitude of albuminuria as well as the prevalence of micro- and macroalbuminuria
      decreased in treatment-resistant hypertensive patients. Since albuminuria is an
      independent renal and cardiovascular risk factor, our findings suggest a
      reduction of renal and cardiovascular risk in these patients.

PMID- 24681018
TI  - AXL receptor tyrosine kinase is increased in patients with heart failure.
AB  - BACKGROUND: AXL is a membrane receptor tyrosine kinase highly expressed in the
      heart and has a conspicuous role in cardiovascular physiology. The role of AXL in
      heart failure (HF) has not been previously addressed. METHODS AND RESULTS: AXL
      protein was enhanced 6-fold in myocardial biopsies of end-stage HF patients
      undergoing heart transplantation compared to controls from heart donors
      (P<0.0001). Next, we performed a transversal study of patients with chronic HF
      (n=192) and a group of controls with no HF (n=67). sAXL and BNP circulating
      levels were quantified and clinical and demographic data were collected. sAXL
      levels in serum were higher in HF (86.3 +/- 2.0 ng/mL) than in controls (67.8 +/-
      2.0 ng/mL; P<0.0001). Also, sAXL correlated with several parameters associated
      with worse prognosis in HF. Linear regression analysis indicated that serum
      creatinine, systolic blood pressure and atrial fibrillation, but not BNP levels,
      were predictive of sAXL levels. Cox regression analysis indicated that high sAXL
      values at enrollment time were related to the major HF events (all-cause
      mortality, heart transplantation and HF hospitalizations) at one year follow-up
      (P<0.001), adding predictive value to high BNP levels. CONCLUSIONS: Myocardial
      expression and serum concentration of AXL is elevated in HF patients compared to
      controls. Furthermore, peripheral sAXL correlates with parameters associated with
      the progression of HF and with HF events at short term follow-up. All together
      these results suggest that sAXL could belong to a new molecular pathway involved
      in myocardial damage in HF, independent from BNP.

PMID- 24681019
TI  - Pre-operative inflammation and post-operative atrial fibrillation in coronary
      artery bypass surgery.

PMID- 24681020
TI  - Time dependent changes in high density lipoprotein cholesterol and cardiovascular
      risk.
AB  - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is a strong inverse
      predictor of cardiovascular events. The aim of the current study was to evaluate
      the correlation between changes in HDL-C and subsequent cardiovascular events.
      METHODS: Study population comprised 13,037 subjects free of cardiovascular
      disease with a mean follow up of 6 +/- 3 years. Low HDL-C was defined as < 40
      mg/dl for men and <50mg/dl for women. Participants were divided into three groups
      based on HDL-C levels at the first and second baseline visits: persistently-low
      HDL-C (LL); persistently-high HDL-C (HH); and those with high HDL-C in a one
      visit only: intermittently high HDL-C (LH/HL). The primary endpoint was the first
      occurrence of a cardiovascular event. RESULTS: A total of 529 (4.1%) incident
      events occurred during follow-up. HDL-C levels increased significantly between
      the two landmark visits (47.5 +/- 12.6 vs. 48.1 +/- 12.2, p<0.001). Kaplan-Meier
      survival analysis showed that the cumulative probability of cardiovascular events
      at 6 years was highest among subjects in the LL group (7.6%), and similar among
      LH/HL and HH groups (3.3% and 4%, respectively; log-rank p=0.001). Multivariate
      Cox regression analysis, with HDL-C as time-dependent covariate, showed that
      subjects with persistently low HDL-C during follow up experienced a 51% increased
      cardiovascular risk compared with subjects with persistently high HDL-C
      (p=0.026). Subjects with intermittently high HDL-C during follow up experienced
      similar risk to those with persistently high HDL-C (HR=1.02; p=0.89).
      CONCLUSIONS: Variations in HDL-C levels during follow-up are associated with
      subsequent cardiovascular risk. Patients who retain low HDL-C levels are at the
      cardiovascular highest risk.

PMID- 24681021
TI  - Sinoatrial node electrical activity modulates pulmonary vein arrhythmogenesis.
AB  - BACKGROUND: Sinoatrial node (SAN) dysfunction increases the occurrences of atrial
      fibrillation (AF). The pulmonary veins (PVs) play a critical role in the
      pathophysiology of AF. The purpose of this study was to evaluate whether SAN
      electrical activity can modulate PV arrhythmogenesis. METHODS: Conventional
      microelectrodes and multi-electrode array system were used to simultaneously
      record the electrical activity and conduction properties of rabbit SAN and PV
      tissue preparations with and without SAN-PV interruptions before and after
      perfusion with Anemonia sulcata toxin (ATX)-II (100 nM) or isoproterenol (1 MUM).
      RESULTS: ATX-II significantly increased PV beating rates, which overdrove SAN
      electrical activity with the occurrences of PV burst firings in 5 (56%) of 9
      tissue preparations, and induced SAN-PV conduction block in 6 (67%) of 9
      preparations. After SAN-PV disconnection, ATX-II induced burst firing and early
      afterdepolarizations in 8 (89%) of 9 PVs. Moreover, the multi-electrode array
      found that ATX-II reversed the electrical conduction between the SAN and PV with
      an increase in electrical activity from 1.8 +/- 0.6 to 2.9 +/- 0.6 Hz (P<0.05) in
      SAN-PV preparations (n=7). In contrast, isoproterenol did not reverse electrical
      conduction between the SAN and PV with an increase in electrical activity from
      1.8 +/- 0.2 to 3.0 +/- 0.3 Hz (P<0.005) in SAN-PV preparations (n=7).
      CONCLUSIONS: SAN electrical activity modulates PV arrhythmogenesis. SAN-PV
      conduction blocks can increase PV arrhythmogenesis.

PMID- 24681023
TI  - Arrhythmogenic cardiomyopathy and provocable Brugada ECG in a patient caused by
      missense mutation in plakophilin-2.

PMID- 24681022
TI  - Statin use and incident dementia: a nationwide cohort study of Taiwan.
AB  - BACKGROUND: Statins are widely used in clinical treatment. However, an U.S. Food
      and Drug Administration issued health alert has raised concerns for the adverse
      effects of statin-associated confusion and memory loss in the elderly people. It
      is necessary to clarify the relationship between statin use and risk of incident
      dementia as well as whether class effects exist. METHODS: In this population
      based retrospective cohort study, total 33,398 patients aged >= 60 years were
      selected from a subset of the Taiwan National Health Insurance Research Databases
      and followed up for tracking the occurrence of any type of dementia from 2000 to
      2010. The Cox proportional hazards models were used. RESULTS: Compared to
      nonusers, statin users had a significantly lower risk of incident dementia
      (hazard ratio [HR], 0.78; 95% CI, 0.72-0.85, p<0.001). The potency and the
      cumulative duration of statin utilized were associated with the reducing risk of
      dementia. After stratifying by gender, the risk of incident dementia was lower in
      female statin users (HR, 0.76; 95% CI, 0.68-0.85, p<0.001) than in male statin
      users (HR, 0.86; 95% CI, 0.75-0.98, p=0.024). Higher potency and longer
      cumulative duration of statin use were required for reducing the risk of incident
      dementia in male patients than in female patients. CONCLUSION: Statin use was
      associated with a significantly lower risk of dementia in the elderly patients in
      Taiwan. The potency and the cumulative duration of statin utilized played
      critical roles.

PMID- 24681025
TI  - Decompensated chronic heart failure > Takotsubo syndrome versus Takotsubo
      syndrome > decompensated chronic heart failure: two plausible inverse parallels.

PMID- 24681024
TI  - Multidisciplinary approach to the treatment of cardiac AA amyloidosis and aortic
      stenosis due to Castleman's disease: a hybrid therapy with tocilizumab and aortic
      valve replacement.

PMID- 24681026
TI  - Nontarget-to-nontarget interval determines the nontarget P300 in an auditory
      equiprobable Go/NoGo task.
AB  - Increases in the target-to-target interval (TTI) systematically enhance the
      amplitude of the target P300 ERP component. Research examining changes in
      nontarget P300 related to nontarget-to-nontarget interval (NNI) or sequential
      probability manipulations has produced inconsistent results, with some studies
      reporting no enhancement in nontarget P300 and others finding response profiles
      analogous to TTI effects. Our aim was to clarify these differences. All
      participants completed a specially designed auditory equiprobable Go/NoGo task
      with manipulations of TTI and NNI while their EEG activity was recorded. P300
      amplitudes were extracted using temporal PCA with Varimax rotation. P3b to
      targets and nontargets increased systematically as respective TTIs/NNIs
      increased, but this change did not differ between stimulus types. The Slow Wave
      did not show any effect of interval, but was more positive to targets than
      nontargets when interval was collapsed. P3b findings show that matching-stimulus
      interval effects are not restricted to targets, but discrepancies relative to
      previous research suggest that NNI effects in P3b may depend on additional
      processing of nontarget stimuli.

PMID- 24681027
TI  - A novel silver iodide metalo-drug: experimental and computational modelling
      assessment of its interaction with intracellular DNA, lipoxygenase and
      glutathione.
AB  - The new mixed ligand silver(I) complex of formula [AgI(TPP)2(MBZT)] (1) was
      obtained by reacting 2-mercapto-benzothiazole (MBZT) with triphenylphosphine
      (TPP). The complex was characterized by m.p., vibrational spectroscopy (FT-IR),
      (1)H NMR, UV-vis, ESI-MS spectroscopic techniques and its structure was confirmed
      by X-ray crystallography. Mixed ligand complexes of silver(I) iodide with thiones
      and phosphines are very rare in the literature and to the best of our knowledge
      compound 1 is the first of this kind exhibiting significant biological effects.
      Complex 1 was evaluated for its in vitro cytotoxic activity (cell viability)
      under irradiation with UV light and without irradiation against human cancer cell
      lines: MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), Caki-1
      (renal), A549 (lung), OAW-42 (ovarian), HeLa (cervical) and additionally against
      the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells)
      and normal immortalized human mammary gland epithelial cell line (MTSV17) with
      SRB assay. The results showed that 1 mediates a strong cytotoxic response to the
      tested normal and cancer cell lines. It exhibits equal activity against MDA-MB
      231 cells where estrogen receptors (ERs) are devoid with the one against MCF-7
      where ERs are present. Molecular docking studies have shown that 1 is docked in
      the different pocket than that of the ERs modulators. The binding affinity of 1
      towards the intracellular molecules DNA and lipoxygenase (LOX) was studied for
      the evaluation of the mechanism of its cytostasis. The binding constant (Kb) of 1
      towards CT-DNA was calculated by UV-Vis and fluorescent spectra suggesting
      intercalation or electrostatic interactions of 1 into DNA. Docking studies on DNA
      complex interactions confirm the binding of 1. Moreover, the influence of complex
      1 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by
      the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. In
      addition, since the deactivation of cisplatin caused by glutathione, seems to be
      an important determinant of its cytotoxic effects, the reaction of 1 with
      glutathione (GSH) was investigated by UV-absorption spectroscopy. 

PMID- 24681028
TI  - Semisynthesis, ex vivo evaluation, and SAR studies of coumarin derivatives as
      potential antiasthmatic drugs.
AB  - Asthma is a chronic inflammatory disorder that causes contraction in the smooth
      muscle of the airway and blocking of airflow. Reversal the contractile process is
      a strategy for the search of new drugs that could be used for the treatment of
      asthma. This work reports the semisynthesis, ex vivo relaxing evaluation and SAR
      studies of a series of 18 coumarins. The results pointed that the ether
      derivatives 1-3, 7-9 and 13-15 showed the best activity (Emax = 100%), where
      compound 2 (42 MUM) was the most potent, being 4-times more active than
      theophylline (positive control). The ether homologation (methyl, ethyl and
      propyl) in position 7 or positions 6 and 7 of coumarins lead to relaxing effect,
      meanwhile formation of esters generated less active compounds than ethers. The
      SAR analysis showed that it is necessary the presence of two small ether groups
      and the methyl group at position 4 (site 3) encourage biological activity through
      soft hydrophobic changes in the molecule, without drastically affecting the
      cLogP. 

PMID- 24681029
TI  - Mutation in the type II collagen gene (COL2AI) as a cause of primary
      osteoarthritis associated with mild spondyloepiphyseal involvement.
AB  - OBJECTIVE: To define the clinical, radiologic and molecular characteristics of a
      patient with early progressive osteoarthritis and mild spondyloepiphyseal
      dysplasia. METHODS: We describe an 18-year-old girl with early progressive
      osteoarthritis and mild spondyloepiphyseal dysplasia. The index case underwent a
      physical examination, anthropometric measurements and radiologic and laboratory
      studies. DNA of the patient and her only living parent (mother) was sequenced for
      the type II collagen gene (COL2A1). RESULTS: Mild scoliosis was noticed in the
      proband at the age of 13 years. At the same age, she began to have arthralgia in
      almost all the joints and osteoarthritis progressed fast, necessitating a hip,
      knee and ankle prosthesis at the age of 18 years. She was eumorphic with no
      ocular or hearing abnormalities. Molecular testing of the COL2A1 gene revealed a
      p.Gly204Val mutation. The mutation was absent in the healthy mother. CONCLUSION:
      This patient provides further proof that an early osteoarthritic phenotype can be
      caused by a mutation in the COL2A1 gene.

PMID- 24681030
TI  - Prognosis of patients with acute respiratory distress syndrome on extracorporeal
      membrane oxygenation: the impact of urine output on mortality.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been utilized for
      patients in critical condition, including life-threatening respiratory failure
      and postcardiotomy cardiogenic shock. This study analyzed the outcomes of
      patients with acute respiratory distress syndrome (ARDS) treated by ECMO and
      identified the relationship between prognosis and urine output (UO) obtained on
      the first day of ECMO support. METHODS: This study reviewed the medical records
      of 81 ARDS patients after ECMO support on a specialized cardiovascular surgery
      intensive care unit of a tertiary care university hospital between May 2006 and
      December 2011. Demographic, clinical, and laboratory variables were
      retrospectively collected as survival predictors. RESULTS: The overall mortality
      rate was 55.5%. A multiple logistic regression analysis indicated that the Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score, mean arterial
      pressure, platelet count, and UO on day 1 of ECMO support were independent risk
      factors for hospital mortality. By using the areas under the receiver operating
      characteristic (AUROC) curve, UO obtained on the first day of ECMO support
      demonstrated good discriminative power (AUROC 0.754 +/- 0.056, p < 0.001). Urine
      output had the best discriminative power, the best Youden index, and the highest
      overall correctness of prediction. Cumulative survival rates at the 6-month
      follow-up differed significantly (p < 0.001) for UO 1,432 mL or greater on day 1
      of ECMO support versus those with UO less than 1,432 mL on day 1 of ECMO support.
      CONCLUSIONS: In ARDS patients receiving ECMO support, UO obtained on the first
      day of ECMO support showed good prognostic ability in predicting hospital
      mortality.

PMID- 24681031
TI  - The perimount valve in the aortic position: twenty-year experience with patients
      under 60 years old.
AB  - BACKGROUND: With improved durability of contemporary bioprostheses, surgeons are
      now recommending biologic valves in younger patients. However, long-term outcomes
      of patients younger than 60 years old undergoing biologic aortic valve
      implantation are not well known. METHODS: From November 1991 to March 2011, 144
      patients less than 60 years old underwent aortic valve replacement (AVR) with
      Carpentier-Edwards pericardial valves (Edwards Lifesciences, Irvine, CA). Mean
      follow-up was 10+/-4 years. Outcomes were reported according to published
      guidelines. RESULTS: Seventy-five percent of patients were male, with a mean age
      of 51+/-9 years. Actuarial survival rates including early deaths were 89%+/-3%,
      79%+/-4%, and 57%+/-6% after 5, 10, and 15 years of follow-up, respectively.
      Survival of patients was comparatively lower than a gender- and age-matched
      general population at all time points. The freedom from major adverse cardiac
      events (myocardial infarction, heart failure, hemorrhage, thromboembolic event,
      and endocarditis) was 89%+/-3%, 87%+/-3%, and 75%+/-6% at 5, 10, and 15 years
      after surgery. The freedom rate from prosthetic valve dysfunction was 97%+/-2%,
      84%+/-4%, and 57%+/-6% at 5, 10, and 15 years after surgery. Patients with a
      diagnosis of structural valve deterioration (29 of 37, 78%) underwent reoperation
      11+/-5 years after the initial valve replacement with no perioperative mortality.
      CONCLUSIONS: In patients younger than 60 years undergoing AVR, the Carpentier
      Edwards Perimount bioprosthesis provided satisfactory clinical outcomes. However,
      late survival was inferior to an age- and gender-matched population. Structural
      valve deterioration and the need for reintervention were common late after
      implantation, but reoperation for prosthetic valve dysfunction was associated
      with a very low risk of mortality.

PMID- 24681032
TI  - Acute bowel ischemia after heart operations.
AB  - Acute bowel ischemia is a perioperative complication that is frequently
      unrecognized as a cause of death after cardiac surgical procedures, with an in
      hospital mortality of 50% to 100%. In recent years, controversy regarding the
      most appropriate approach to resolve clinical or laboratory suspicion and the
      limited therapeutic options have led to very little improvement in patient
      prognosis. This article reviews the related literature examining the actual
      prevalence, pathophysiologic mechanisms, predisposing factors, diagnostic tests,
      and therapeutic approaches providing a glance at new promising tools in
      diagnostic workup. 

PMID- 24681033
TI  - Video-assisted thoracoscopic pneumonectomy: retrospective outcome analysis of 47
      consecutive patients.
AB  - BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) lobectomy is
      widely accepted, VATS pneumonectomy remains an uncommon procedure in patients
      with complicated diseases. METHODS: Of 47 consecutive patients who were planned
      to undergo VATS pneumonectomy from May 2000 to May 2012 at the National Hospital
      Organization Himeji Medical Center, VATS pneumonectomy was completed successfully
      in 46 patients (2.1% conversion rate). Appropriate tissue retraction and
      cooperative dissection of hilum structures under only thoracoscopic visualization
      were applied to all candidates. We retrospectively reviewed morbidity, mortality,
      local disease control, and surgical considerations to evaluate the validity of
      this procedure. RESULTS: All patients had malignant tumors, including 45 with
      primary lung cancer. One patient with a severe adhesion around a tumor required
      conversion to open thoracotomy, with no subsequent specific complications. Of 46
      patients in whom VATS pneumonectomy was completed, the mean operation time was
      159 minutes and the mean blood loss was 258 g. Surgery-related death occurred in
      1 patient (mortality rate: 2.2%) with recurrent heart failure after discharge.
      Seven patients (15.2%) had major complications defined as grade 3 or higher
      (Common Terminology Criteria for Adverse Effects, version 4.0) within 30 days
      postoperatively; however, no patients exhibited secretion retention that required
      bronchoscopy. There were no patients with locoregional recurrence within usual
      lymph node dissection areas and the ipsilateral thoracic cavity among 44 patients
      with primary lung cancer who underwent VATS pneumonectomy, with the median follow
      up time of 27 months. CONCLUSIONS: Video-assisted thoracoscopic surgery
      pneumonectomy has developed into a common procedure with acceptable damage and
      lower morbidity among selected patients with complicated diseases.

PMID- 24681034
TI  - Training in minimally invasive lobectomy: thoracoscopic versus robotic
      approaches.
AB  - BACKGROUND: Skills required for thoracoscopic and robotic operations likely
      differ. The needs and abilities of trainees learning these approaches require
      assessment. METHODS: Trainees performed initial components of minimally invasive
      lobectomies using thoracoscopic or robotic approaches. Component difficulty was
      scored by trainees using the NASA task load index (NASATLX). Performance of each
      component was graded by trainees and attending surgeons on a 5-point ordinal
      scale (naive, beginning learner, advanced learner, competent, master). RESULTS:
      Eleven surgical trainees performed 87 replications among three lobectomy
      components (divide pulmonary ligament; dissect level 7/8/9 nodes; dissect level
      4/5 nodes). Before performance NASATLX scores did not differ among components or
      between surgical approaches. Trainees' after performance NASATLX scores
      appropriately calibrated task load for the components. After performance NASATLX
      scores were significantly lower for thoracoscopy than before performance
      estimates; robotic scores were similar before surgery and after performance. Task
      load was higher for robotic than for thoracoscopic approaches. Trainees rated
      their performance higher than did attending surgeons in domains of knowledge and
      thinking, but ratings for other domains were similarly low. Ratings for
      performance improved significantly as component performance repetitions
      increased. CONCLUSIONS: Trainees did not differentiate task load among components
      or surgical approaches before attempting them. Task load scores differentiated
      difficulty among initial components of lobectomy, and were greater for robotic
      than for thoracoscopic approaches. Trainees overestimated their level of
      cognitive performance compared with attending physician evaluation of trainee
      performance. The study provides insights into how to customize training for
      thoracoscopic and robotic lobectomy and identifies tools to assess training
      effectiveness.

PMID- 24681035
TI  - Necessity of temporary epicardial pacing wires after surgery for congenital heart
      disease.
AB  - BACKGROUND: Temporary epicardial pacing wires are commonly placed in patients
      undergoing surgery for congenital heart disease. Though often helpful, these
      wires are not without risk. We aimed to identify characteristics that would
      obviate placement of temporary epicardial pacing wires in this patient
      population. METHODS: A prospective observational study was performed on patients
      admitted to the pediatric intensive care unit after surgery for congenital heart
      disease between October 2011 and October 2012. Logistic regression analysis was
      performed to identify independent predictors of patients in whom wires were not
      helpful postoperatively. RESULTS: Wires were placed in 213 of 249 patients. Wires
      were helpful in 50 patients; 23 for diagnostic purposes only, 17 for therapeutic
      purposes only, and 10 for both. On logistic regression analysis, absence of
      intraoperative arrhythmias (p < 0.01), lower arteriovenous O2 difference (p <
      0.01), and shorter duration of cardiopulmonary bypass (p = 0.050) were
      significant predictors of patients in whom wires were not helpful
      postoperatively. Further, the predicted probability based on logistic regression
      model using these 3 variables correctly identified 93% of patients who did not
      need pacing wires. Four complications (1.9%) related to wires occurred, including
      1 episode of life-threatening bleeding that was found, during emergent
      exploration, to be due to atrial perforation at the wire insertion site.
      CONCLUSIONS: Temporary epicardial pacing wires are not necessary in many patients
      recovering from surgery for congenital heart disease. A conservative approach to
      their use may therefore be warranted.

PMID- 24681036
TI  - Nonspecific pleuritis: optimal duration of follow-up.
AB  - BACKGROUND: Nonspecific pleuritis (NSP) is a frequent diagnosis after parietal
      pleural biopsy, but the clinical significance of this finding and need for
      further follow-up have not been firmly established. Previous reports suggest that
      5% to 25% of patients with NSP are subsequently diagnosed with pleural
      malignancy. METHODS: Our pathology database was queried for patients with
      histologic evidence of NSP from January 01, 2001, to December 31, 2012 (n = 413).
      Patients with less than 1 year of follow-up after biopsy, diagnosis of empyema,
      tuberculous pleuritis, active systemic connective tissue disease or vasculitis,
      or active malignancy were excluded (n = 327). The remaining patients were
      included and their medical records were reviewed. RESULTS: Eighty-six patients
      were included. Mean follow up was 1,824 +/- 1,032 days (range, 409 to 4,599
      days). Three of the 86 patients with NSP (3.5%) were subsequently diagnosed with
      pleural malignancy. All 3 patients were found to have mesothelioma with a mean
      time from biopsies to diagnosis of 205 +/- 126 days (range, 64 to 306 days).
      Twenty-two of 86 patients (25.5%) had a possible identifiable cause of pleural
      inflammation (benign disease). After exclusion of these 22 patients, the
      incidence of malignancy was 3 of 64 (4.7%). CONCLUSIONS: The incidence of
      subsequent pleural malignancy (mesothelioma) among patients found to have NSP
      based on pleural biopsy was 3.5%. Occult mesothelioma in patients with NSP will
      most likely be diagnosed within 1 year of the initial pleural biopsy; therefore,
      these patients should be followed for a minimum of 1 year to allow for timely
      detection of occult pleural malignancy.

PMID- 24681037
TI  - Risk factors for lymph node metastases and prognosticators of survival in
      patients undergoing pulmonary metastasectomy for colorectal cancer.
AB  - BACKGROUND: Systematic lymph node dissection is not routinely performed in
      patients undergoing pulmonary metastasectomy (PM) of colorectal cancer. The aim
      of the study was to identify risk factors for lymph node metastases (LNM) and to
      determine prognosticators for survival in colorectal cancer patients with
      pulmonary metastases. METHODS: We retrospectively reviewed our prospective
      database of 165 patients with colorectal cancer undergoing PM and systematic
      lymph node dissection with curative intent from 1999 to 2009. The chi(2) test,
      regression analyses, Kaplan-Meier analyses, log rank tests, and Cox regression
      analyses were used to determine prognosticators for LNM and survival. RESULTS:
      The prevalence of LNM was 22.4%. Lymph node metastases were more often detected
      in case of rectal cancer and if anatomic resections in term of segmentectomy or
      lobectomy had to be performed for PM. The number of pulmonary metastases showed a
      nonlinear association with the risk of positive postoperative LNM. For 1 to 10
      pulmonary metastases, each additional pulmonary metastasis conferred a 16%
      increase in risk for LNM. Rectal cancer, M-status of the primary tumor, number of
      pulmonary metastases, and disease progression during pre-PM chemotherapy were
      independent prognosticators for survival. Lymph node metastases were not an
      independent prognosticator. CONCLUSIONS: Rectal cancer, required anatomic
      resections, and multiple metastases were risk factors for LNM. Rectal cancer, M
      status of the primary tumor, number of pulmonary metastasis, and disease
      progression during pre-PM chemotherapy were independent negative predictors of
      survival, stratifying patients with poor prognosis who may benefit from
      chemotherapy before or after PM.

PMID- 24681038
TI  - Surgical management of congenital pulmonary malformations after the first decade
      of life.
AB  - BACKGROUND: Most congenital pulmonary malformations are discovered early in life,
      but some are diagnosed in adulthood. We evaluated patients treated surgically
      after the first decade of life. METHODS: All patients who underwent surgical
      treatment for a congenital pulmonary malformation diagnosed after 10 years of age
      at a single institution from 1997 to 2012 were evaluated for presenting symptoms,
      surgical management, perioperative outcomes, and symptom resolution. RESULTS:
      Twenty-two patients met the inclusion criteria. The most common malformations
      were pulmonary sequestration (n = 12, 55%), congenital cystic adenomatoid
      malformation (n = 2, 9%), and bronchial agenesis (n = 2, 9%). The median age at
      diagnosis was 36 years (range, 10-66 years). The most common presenting symptoms
      were dyspnea (n = 6, 27%) and hemoptysis (n = 4; 18%); 4 (18%) asymptomatic
      patients received diagnoses. The median duration of symptoms before operation was
      14 months. An emergency room visit or hospitalization occurred in 11 patients
      (50%) before their referral for surgical evaluation. The surgical approach was
      thoracotomy for 7 patients (32%) and thoracoscopy for 15 patients (68%). All
      vascular anomalies requiring a pneumonectomy (n = 3, 14%) were done by a
      thoracotomy, and 83% (10/12) of pulmonary sequestrations were treated
      thoracoscopically. The median hospital stay was 3 days. There were no
      perioperative deaths, and minor morbidity occurred in 4 patients (18%). Complete
      resolution of symptoms after operation occurred in 94% (16/17) of patients, with
      a median follow-up time of 3 weeks. CONCLUSIONS: Early surgical management of
      congenital pulmonary malformations found after the first decade of life is
      recommended to control symptoms and avoid hospitalizations. Most adult pulmonary
      sequestrations can be treated with minimally invasive techniques.

PMID- 24681039
TI  - Evaluation of anti-inflammatory and mechanism of action of extract of
      Macrosiphonia longiflora (Desf.) Mull. Arg.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Macrosiphonia longiflora (Desf.) Mull. Arg
      (Apocynaceae), popularly known as 'velame' and 'velame branco', is a native
      subshrub that grows in the Brazilian Cerrado. This plant is widely used in
      traditional medicine in the form of decoction and infusion, particularly as anti
      inflammatory, depurative, anti-rheumatic, antisyphilitic and antiulcer remedy.
      There is no available information in the literature that has addressed its
      pharmacological activity and phytochemical analysis. AIM OF THE STUDY: This study
      aimed to evaluate the anti-inflammatory pharmacological profile of the
      hydroethanolic extract of Macrosiphonia longiflora, using in vivo and in vitro
      acute inflammation experimental models, as well as investigate the roles of
      cytokines and nitric oxide in its mechanism of action, and including
      phytochemical analysis constitution of its hydroethanolic extract. MATERIALS AND
      METHODS: Hydroethanolic (70%) extract of Macrosiphonia longiflora (HEMl) was
      prepared by maceration. The preliminary phytochemical analysis was performed
      according to procedures described in the literature. Selected secondary
      metabolites detected were quantified by spectrophotometry and high performance
      liquid chromatography (HPLC). Its cytotoxic potential in Chinese hamster ovary
      (CHO-k1) epithelial cell lines was evaluated using Alamar Blue. in vivo anti
      inflammatory activity was evaluated with carrageenan- and dextran-induced paw
      edemas, carrageenan-induced pleurisy in rats and lipopolysaccharide (LPS)-induced
      peritonitis in mice. The in vitro anti-inflammatory activity was evaluated using
      RAW 264.7 cells stimulated with LPS and interferon (INF)-gamma. Effects of HEMl
      on the inflammatory cytokines (IL-1beta, IL-10, IL-17, INF-gamma and TNF-alpha)
      concentrations in the peritoneal lavage were evaluated using commercial ELISA
      kits, while the Griess method was employed to determine nitric oxide (NO)
      concentrations in the peritoneal lavage, as well as in the supernatants of RAW
      264.7 cells. RESULTS: Preliminary phytochemical analysis, revealed the presence
      of phenolics compounds, terpenoids, alkaloids and flavonoids. Spectrophotometric
      analysis revealed the presence of relatively high content of phenolics and
      flavonoids in HEMl. HPLC analysis confirmed the presence of the quantified
      compounds and demonstrated the presence of ellagic acid in the detected matrix of
      compounds. HEMl appeared to be non-cytotoxic. It effectively inhibited (p<0.05)
      paw edema induced by carrageenan and dextran. Furthermore, HEMl also
      significantly reduced exudates volume and leukocyte migration in the carrageenan
      induced pleurisy and LPS-induced peritonitis, neutrophils counts in LPS-induced
      peritonitis. HEMl also acts by effectively inhibiting the following inflammatory
      cytokines: IL-1beta and IL-10 levels in the peritoneal lavage, but had no effect
      on IL-17 level in the peritonitis model. In addition, HEMl had no effect on the
      levels of tumor necrosis factor alpha (TNF-alpha) present in the peritoneal
      lavage and cells supernatants. The concentration of NO, as assessed by
      measurement of nitrite (NO2(-)), showed that pretreatment with HEMl reduced NO
      significantly in the peritoneal lavage and in RAW 264.7 cells co-stimulated with
      LPS and INF-gamma. CONCLUSION: The results obtained in this study indicate that
      HEMl possesses very low cytotoxic potential. In addition, it demonstrated a
      potent anti-inflammatory activity in both the in vivo and in vitro models of
      acute inflammation. The anti-inflammatory effect is partly related to the
      inhibition of IL-1beta, IL-10, and nitric oxide releases, but independent of TNF
      alpha and IL-17 modulation. Phytochemical analysis revealed the predominant
      presence of the flavonoids (naringin, rutin, myricetin, morin, quercetin, (+/-)
      naringenin, and luteolin) and phenols (ellagic acid), which are possibly involved
      in the anti-inflammatory effect of HEMl. The current study provided supportive
      evidence for the popular use of HEMl in the treatment of inflammatory conditions,
      and shed more light on the possible roles of the inflammatory cytokines in its
      mechanisms of action as anti-inflammatory agent.

PMID- 24681040
TI  - Polarity of extracts and fractions of four Combretum (Combretaceae) species used
      to treat infections and gastrointestinal disorders in southern African
      traditional medicine has a major effect on different relevant in vitro
      activities.
AB  - ETHNOPHARMACOLOGICAL IMPORTANCE: Gastrointestinal disorders and infections are
      the major pathoaetiologies of diarrhoea causing many problems in human health and
      animal production. Many Combretum species are used in traditional medicine to
      treat infectious diseases including diarrhoea and many other ailments by rural
      people in Africa and Asia. Much of the work done to date on this genus was on the
      non-polar or intermediate polarity components. Some parameters that may cause
      diarrhoea and the evaluation of more polar extracts have apparently not been
      investigated. AIMS: The polar components were extracted and fractionated by
      solvent-solvent fractionation to yield fractions with different polarities. The
      activity of these fractions on different parameters that could be involved in
      factors associated with diarrhoea was investigated. The cytotoxic activities of
      the extracts were also determined to evaluate the potential of these extracts to
      combat diarrhoea in production animals. MATERIALS AND METHODS: Phenolic-enriched
      leaf extracts of Combretum bracteosum (COB), Combretum padoides (COP), Combretum
      vendae (COV) and Combretum woodii (COW) were obtained by extracting with a
      mixture of 70% acetone acidified with 1% HCl and n-hexane. Acetone was removed
      from a portion of the 70% acetone extract and it was sequentially treated by
      solvent-solvent fractionation with dichloromethane, ethyl acetate, and butanol to
      yield fractions with a large variation in polarity. The phenolic constituents of
      the extracts and fractions were determined using standard procedures The
      antioxidant activities were determined using the 2,2-diphenyl-1-picrylhydrazyl
      (DPPH); 2,2'-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid (ABTS(+))
      radical scavenging, ferric reducing antioxidant power (FRAP) methods and lipid
      peroxidation inhibitory capacity standard methods. The ferric reducing
      antioxidant activities of the fractions were also determined. The minimum
      inhibitory concentrations (MICs) of the crude extracts and fractions against four
      bacterial and three fungal strains were assessed with a microplate serial
      dilution method. Cyclooxygenase (COX) and lipoxygenase (LOX) enzyme inhibitory
      assays and cytotoxicity studies against Vero cells were also carried out. RESULT:
      Some of the fractions had much higher antioxidant activity than the positive
      controls. The average EC50 values of the extracts for the DPPH and ABTS
      antioxidant assays were 0.21-12ug/ml (COP), 0.25-16ug/ml (COV), 0.33-9.41ug/ml
      (COW) and 4.97-85ug/ml (COB) respectively while the mean EC50 values for the
      positive controls ascorbic acid and trolox were 1.28-1.51 and 1.02-1.19ug/ml
      respectively. All the crude extracts inhibited lipid peroxidation of linoleic
      acid by more than 80% at a concentration of 64 ug/ml. COP had the highest
      antibacterial activity with MICs ranging between 19-2500ug/ml, followed by COV
      with MICs ranging between 39-625ug/ml; COW and COB had similar MICs ranging
      between 39-2500ug/ml. COP also had the highest antifungal activity with MICs
      between 19-625ug/ml. The MIC for COW and COV ranged from 19 to 1250 ug/ml. COB
      had the lowest antifungal activity (MIC values were between 39 and 625 ug/ml). In
      general non-polar fractions had a high antimicrobial activity and polar fractions
      had a high antioxidant activity. The extracts had no activity against COX 1 and 2
      enzymes in the anti-inflammatory assay but had good lipoxygenase inhibition. The
      crude extracts had high concentration of hydrolysable tannin (gallotannin). A
      good correlation (R(2)= 0.99) was found between the antioxidant activity and
      total tannin content indicating that, gallotannins may be responsible for the
      antioxidant activity. CONCLUSION: The results obtained in this study with more
      polar extracts indicate that the use of extracts of these plant species as
      antidiarrhoeal agents may have a scientific basis. The extractant used here
      extracted a much higher percentage of the phytochemicals than acetone. It was
      better for isolating antioxidant compounds (polar) but not good for isolating
      antimicrobial compounds (non-polar) from the same species compared to acetone,
      ethyl acetate, dichloromethane, and hexane.

PMID- 24681041
TI  - MicroRNA-216b/Beclin 1 axis regulates autophagy and apoptosis in human Tenon's
      capsule fibroblasts upon hydroxycamptothecin exposure.
AB  - Proliferation and fibrosis of human Tenon's fibroblasts (HTFs) have significantly
      challenged the outcome of glaucoma filtration surgery. Hydroxycamptothecin (HCPT)
      is considered as a potential chemical to overcome this issue as it was previously
      shown that HCPT inhibited cell proliferation and induced apoptosis in
      fibroblasts. Here, we further dissected the molecular pathway, through which the
      HCPT inhibit the proliferation of HTFs. We showed that HCPT induced significant
      autophagy as well as apoptosis, two self-destructive processes, and down
      regulated the expression of miR-216b in HTFs. Overexpression of miR-216b in HTFs
      suppressed the autophagy and apoptosis induced by HCPT, whereas silence of miR
      216b led to effects that were similar to those caused by the treatment with HCPT.
      Further, we showed that miR-216b could directly target a specific fragment in the
      3' untranslated region of Beclin 1 as demonstrated by luciferase assay, and
      consequently decreased the expression of Beclin 1. Consistently, knocking down
      Beclin 1 significantly decreased HCPT-triggered autophagy and apoptosis, and
      increased the viability of HTFs treated with HCPT, thus implicating that Beclin 1
      functions as a pro-apoptotic molecule in this circumstance. Altogether, we
      concluded that miR-216b regulated both autophagy and apoptosis by modulating
      Beclin 1 in HTFs treated with HCPT. We also demonstrated that HCPT-induced
      autophagy is one of the agent's anti-proliferative effects.

PMID- 24681042
TI  - Interrelated factors favoring physical performance and activity in older adults
      from the NuAge cohort study.
AB  - OBJECTIVES: Contribute evidence towards the complex interrelationships of body
      composition, physical performance and physical activity (PA) in an older
      population to assist in decisions for maintaining functional capacity in older
      adults. DESIGN: This is a cross-sectional analysis of an existing dataset in
      which a literature-supported model linking together the variables of interest is
      tested using path analysis. A proposed model with age, sex, energy intake and
      chronic diseases as predictors associated with body composition components, while
      the latter associated with physical performance and with PA acting both as a
      predictor and as an outcome of physical performance. PARTICIPANTS: A sample of
      847, community dwellers, non-diabetic older men and women from the Quebec
      Longitudinal Study on Nutrition and Successful Aging (NuAge Study). MEASUREMENTS:
      Physical performance tests were reduced to two indices: strength and mobility.
      Muscle mass index (MMI; kg/height(2)) and % body fat were derived from DXA and
      bioimpedance analysis (BIA). PA was assessed by the Physical Activity Scale for
      the Elderly (PASE) and energy intakes were calculated from 24-hour food recalls.
      Data from the NuAge dataset served to test the relationships. The proposed model
      was evaluated using indices of fit. RESULTS: Significant associations were found
      for MMI and % body fat with mobility (beta -0.11 and -0.02, respectively), and
      for MMI with strength (beta=0.60). PA was associated with MMI (beta=0.02) and
      negatively with % body fat (beta=-0.16), while mobility associated with PA
      (beta=0.65). Our hypothesized model, with some paths added, fit the data: chi
      square=4.64, root mean square error of approximation (RMSEA)=0. CONCLUSIONS: PA
      has desirable associations with body composition in older adults and mobility is
      associated with PA. These results stress the importance of taking into account
      the prior level of mobility when recommending PA for this age group. This model
      could explain in part the complex interrelationships that occur with aging and
      the potential factors that could be targeted to assist older individuals in
      maintaining functional capacity.

PMID- 24681043
TI  - Larvicidal activity of Ipomoea cairica (L.) Sweet and Ageratina adenophora
      (Spreng.) King & H. Rob. plant extracts against arboviral and filarial vector,
      Culex quinquefasciatus Say (Diptera: Culicidae).
AB  - Culex quinquefasciatus Say, an arboviral and filarial vector, is one of the most
      widespread mosquitoes in the world, and insecticide-resistant populations have
      been reported worldwide. Due to the emergence of resistance in C.
      quinquefasciatus plant based products or plant extracts may be alternative
      sources in integrated vector management program. The present study was carried
      out to establish the larvicidal activities of crude solvent extracts prepared
      from flowers and leaves of Ipomoea cairica and Ageratina adenophora against third
      instar larvae of C. quinquefasciatus as target species. The plant extracts were
      prepared with petroleum ether, chloroform and methanol solvents using sequential
      extraction method to determine the best extractant for subsequent isolation and
      characterization of active ingredient. The total yield of plant extract in the
      Soxhlet extraction ranged between 0.79% and 19.35%. The qualitative phytochemical
      study of the plant extracts from different solvents showed the presence of
      alkaloids, flavonoids, phenols, terpenes, saponins and tannins in different
      combinations. I. cairica and A. adenophora plant extracts were found to be
      effective against third instar larvae of C. quinquefasciatus causing 77-100%
      mortality at 48h. Highest mortality was observed at 500ppm and the order of
      larvicidal action was observed to be of methanol extract of I. cairica
      flower>petroleum ether extract of A. adenophora leaf>chloroform extract of I.
      cairica leaf. High mortality (100%) with low LC50 and LT50 were observed in
      methanolic flower extract (LC50 - 8.43ppm; LT50 - 2.51h at 48h) of I. cairica,
      and petroleum ether (LC50 - 133.56ppm; LT50 - 9.45h at 48h) leaf extract of A.
      adenophora. Lethal concentration (LC50 and LC90) values gradually decreased with
      the exposure periods, lethal time (LT50 and LT90) decreased with the
      concentration in bioassay experiment with the crude plant extracts. There was a
      significant correlation (three-way factorial ANOVA) was noticed among
      concentration of the plant extracts, exposure time and solvent extraction in
      relation to larval mortality (P<0.0001), which indicates that larval mortality is
      concentration dependent as well as time-dependent. Further in-depth study is
      needed to identify and characterize the active components present in the plant
      solvent extracts and implement the effective arboviral and filarial mosquito
      vector management program. 

PMID- 24681044
TI  - ACC/AHA statement on cost/value methodology in clinical practice guidelines and
      performance measures: a report of the American College of Cardiology/American
      Heart Association Task Force on Performance Measures and Task Force on Practice
      Guidelines.

PMID- 24681045
TI  - Storage stability and skin permeation of vitamin C liposomes improved by pectin
      coating.
AB  - A transdermal drug delivery system was prepared by high methoxyl pectin (HMP) or
      low methoxyl pectin (LMP) coated vitamin C liposomes. HMP coated vitamin C
      liposomes (HMP-L) and LMP coated vitamin C liposomes (LMP-L) exhibited an
      increase in average diameter (from 66.9 nm to 117.3 nm and 129.6 nm,
      respectively), a decrease in zeta potential (from -2.3 mV to -23.9 mV and -35.5
      mV, respectively), and a similar entrapment efficiency (48.3-50.1%). Morphology
      and FTIR analysis confirmed that pectin was successfully coated on the surface of
      vitamin C liposomes mainly through the hydrogen bonding interactions. Besides,
      HMP-L and LMP-L exhibited an obvious improvement in storage stability, with lower
      aggregation, oxidation of lipid and leakage ratio of vitamin C from liposomes,
      and LMP-L showed better physicochemical stability than HMP-L. Moreover, skin
      permeation of vitamin C was improved 1.7-fold for HMP-L and 2.1-fold for LMP-L
      after 24 h, respectively, compared with vitamin C nanoliposomes. Therefore, this
      study suggested that pectin coated liposomes, especially the LMP-L, could be a
      promising transdermal drug delivery system with better storage stability and skin
      permeation.

PMID- 24681046
TI  - A simple and general method for preparing antibody-PEG-PLGA sub-micron particles
      using electrospray technique: an in vitro study of targeted delivery of cisplatin
      to ovarian cancer cells.
AB  - Cisplatin-encapsulating maleimide-polyethylene glycol- Poly(d,l-lactic-co
      glycolide) (cis-encapsulating mal-PEG-PLGA) particles were produced using the
      electrospray technique and bioconjugated with CD44 monoclonal antibody, targeting
      the counterpart receptor. The produced suspension of cis-encapsulating CD44-PEG
      PLGA particles contains an antibody loading of 12.65-15.17 MUg/mL and efficiently
      targets a CD44-overexpressed ovarian cancer cell line, such as CP70 and SKOV-3,
      within 6h of treatment, which was determined by Bradford assay,
      immunofluorescence analysis, and confocal laser scanning microscopic (CLSM)
      study. Most importantly, no tedious multi-step bioconjugation procedures are
      needed to synthesize mal-PEG-PLGA vehicles for antibody and drug loading,
      avoiding the undesirable hydrolysis of mal-PEG moiety and so successfully
      generating the cis-encapsulating mal-PEG-PLGA particles within one step. After
      conjugation of the CD44 antibody, the produced cis-encapsulating CD44-PEG-PLGA
      particles exhibited a better anti-proliferative ability against ovarian cancer
      cells compared to free form of cisplatin and PLGA particles without CD44
      conjugation. Notably, the cis-encapsulating CD44-PEG-PLGA particles have
      approximately 10-14% greater the anti-proliferative ability against CP70 and SKOV
      3 cells at a concentration of 1.25 MUM, which falls within the concentrations
      used in chemotherapy. The proposed antibody-functionalization strategy represents
      an excellent platform for preparing particles with targeting ability in cancer
      therapy in vitro or in vivo.

PMID- 24681047
TI  - Anticancer activity of Moringa oleifera mediated silver nanoparticles on human
      cervical carcinoma cells by apoptosis induction.
AB  - Silver nanomaterial plays a crucial role in the growing field of nanotechnology
      as there is an increasing commercial demand for silver nanoparticles (AgNPs)
      owing to their wide biological applications. The present investigation aims at
      developing anti-cancerous colloidal silver using Moringa olifera stem bark
      extract. Electron and atomic force microscopic images were taken to analyze the
      surface morphology of the synthesized AgNPs. The effects of synthesized AgNPs
      were tested against human cervical carcinoma cells (HeLa) and cell morphology was
      further evaluated using 4,6-diamidino-2-phenylindole (DAPI) staining. The
      efficiency of green synthesized AgNPs was studied with the help of fluorescence
      activated cell sorting (FACS) and was shown to induce apoptosis through reactive
      oxygen species (ROS) generation in HeLa cells. 

PMID- 24681048
TI  - Molecular arrangements and interconnected bilayer formation induced by alcohol or
      polyalcohol in phospholipid vesicles.
AB  - A self-assembled hybrid phospholipid vesicular system containing various
      penetration enhancers - ethanol, Transcutol and propylenglycol - was prepared and
      characterized. The effects of the different alcohol or polyalcohols structure and
      their concentration on the features of the assembled vesicles were evaluated
      using a combination of different techniques, including cryo-transmission electron
      microscopy, laser light scattering, differential scanning calorimetry, small- and
      wide-angle X-ray scattering and rheological analysis. These techniques allow
      explaining the structural rearrangements of the bilayer assembly due to the
      alcohol or polyalcohol addition. X-ray scattering studies showed that such
      addition at the highest concentration (20%) allowed structure modification to
      oligolamellar vesicles and a bilayer transition to interdigitated phase.
      Rheological studies confirmed the importance of alcohol or polyalcohol in the
      structuring dispersions probably due to a partial tilting of phosphatidylcholine
      acyl chains forming interdigitated and interconnected bilayer vesicles. 

PMID- 24681049
TI  - Investigations into aggregate formation with oppositely charged oil-in-water
      emulsions at different pH values.
AB  - The pH-dependent formation and stability of food-grade heteroaggregates from
      oppositely charged oil-in-water (O/W) emulsions was investigated. After screening
      suitable emulsifiers, 10% (w/w) oil in-water emulsions (d32~1 MUm) were prepared
      at pH 3-7 using a positively charged emulsifier (Na-lauroyl-l-arginine ethyl
      ester; LAE) and four negatively charged ones (citric esters of mono- and
      diglycerides, soy lecithin, sugar beet pectin, and Quillaja saponin). The
      oppositely charged emulsions were then combined at constant pH values at a volume
      flow rate ratio of 1:1. Emulsions and heteroaggregates were characterized by
      their surface charge, particle size distribution and microstructure using dynamic
      and static light scattering as well as confocal laser scanning microscopy. The
      emulsifier type was found to greatly influence the type of heteroaggregates
      formed, as well as the pH value, specifically in combined LAE/Quillaja saponin
      emulsions. Larger aggregates particularly were formed with increasing pH values
      (2.71+/-1.21 to 46.53+/-4.30 MUm from pH 3 to 7, respectively), while LAE/pectin
      aggregates appeared not to be affected by pH over the full pH range investigated
      (3.80+/-2.89 to 3.94+/-2.78 MUm from pH 3 to 7, respectively). Our study thus
      provides valuable first insights into the mechanism of the formation of food
      grade heteroaggregates for later use in food systems.

PMID- 24681050
TI  - Construction of replication competent plasmids of hepatitis B virus subgenotypes
      A1, A2 and D3 with authentic endogenous promoters.
AB  - Hepatitis B virus (HBV) is hyperendemic to southern Africa, with genotype A of
      HBV being the predominant genotype, and subgenotype A1 prevailing. Infection with
      this subgenotype is associated with rapid disease progression, and high frequency
      of hepatocellular carcinoma development. The objectives of our study was to
      construct recombinant 1.28 mer replication competent HBV DNA plasmids of
      subgenotypes A1, A2 and D3 containing authentic endogenous HBV promoters and to
      follow their replication in vitro after transfection of Huh7 cells. We found that
      subgenotype D3 replicated at a lower level, as measured by HBsAg and HBV DNA
      levels, when compared to cells transfected with genotype A. There was no
      difference in the intracellular and extracellular HBsAg between cells transfected
      with subgenotypes A1 or A2. Cells transfected with subgenotype A1 had higher
      levels of intracellular replicative intermediates and HBcAg, and lower
      extracellular expression of HBeAg from days 1 to 3, when compared to cells
      transfected with subgenotype A2. In conclusion, the generation of these
      replication competent clones is an important step in the functional
      characterization of subgenotypes of HBV circulating in Africa and their
      comparison to strains circulating in other geographical regions of the world.

PMID- 24681051
TI  - Molecular double-check strategy for the identification and characterization of
      European Lyssaviruses.
AB  - The "gold standard" for post-mortem rabies diagnosis is the direct fluorescent
      antibody test (FAT). However, in the case of ante-mortem non-neural sample
      material or decomposed tissues, the FAT reaches its limit, and the use of
      molecular techniques can be advantageous. In this study, we developed and
      validated a reverse transcription PCR cascade protocol feasible for the
      classification of samples, even those for which there is no epidemiological
      background knowledge. This study emphasises on the most relevant European
      lyssaviruses. In a first step, two independent N- and L-gene based pan-lyssavirus
      intercalating dye assays are performed in a double-check application to increase
      the method's diagnostic safety. For the second step, characterization of the
      lyssavirus positive samples via two independent multiplex PCR-systems was
      performed. Both assays were probe-based, species-specific multiplex PCR-systems
      for Rabies virus, European bat lyssavirus type 1 and 2 as well as Bokeloh bat
      lyssavirus. All assays were validated successfully with a comprehensive panel of
      lyssavirus positive samples, as well as negative material from various host
      species. This double-check strategy allows for both safe and sensitive screening,
      detection and characterization of all lyssavirus species of humans and animals,
      as well as the rapid identification of currently unknown lyssaviruses in bats in
      Europe. 

PMID- 24681052
TI  - Validation of TaqMan(r) SNP genotyping specificity for rs12979860 of IL-28B:
      modeling primer specificity in vitro.
AB  - Members of the type III interferon gene family arose by gene duplication events
      and have retained a high percent identity both in their coding and non-coding
      regions. In this study, the specificity of a widely used TaqMan((r)) SNP
      genotyping assay for rs12979860 is validated. The 66 bp template for SNP
      genotyping has only 3 bp at one 5' end that vary between IL-28B and IL-28A;
      excluding the rs12979860 SNP itself. Conflicting annealing temperatures were
      found for the mismatched 19 bp primer to IL-28B and IL-28A with in silico melting
      temperature algorithms, or with in vitro dissociation curves. In order to prove
      specificity for IL-28B, an in vitro competition assay was setup with genomic DNA
      and synthetic oligonucleotides. When genomic DNA, containing equimolar
      concentrations of rs12979860 and the homologous region of IL-28A are present, no
      off-target amplification was observed. This SNP genotyping assay is therefore
      specific for rs12979860 and all previously reported results are valid. Finally,
      using a completely synthetic in vitro competition assay it was possible to
      calculate the amount of off-target template that will produce 1/2 the maximum on
      target (VIC) fluorescent signal, a value that is between a C/C genotype and a T/T
      genotype. This value is defined in the manuscript as the half maximum positive
      value, KHPV, and in the present assay KHPV is 15.75+/-0.0721, represented as the
      relative fold increase in the amount of IL-28A over rs12979860. This method will
      be of interest to those performing genotyping on highly conserved gene families.

PMID- 24681053
TI  - A simple and novel modification of comet assay for determination of bacteriophage
      mediated bacterial cell lysis.
AB  - The comet assay is the widely used method for in vitro toxicity testing which is
      also an alternative to the use of animal models for in vivo testing. Since, its
      inception in 1984 by Ostling and Johansson, it is being modified frequently for a
      wide range of application. In spite of its wide applicability, unfortunately
      there is no report of its application in bacteriophages research. In this study,
      a novel application of comet assay for the detection of bacteriophage mediated
      bacterial cell lysis was described. The conventional methods in bacteriophage
      research for studying bacterial lysis by bacteriophages are plaque assay method.
      It is time consuming, laborious and costly. The lytic activity of bacteriophage
      devours the bacterial cell which results in the release of bacterial genomic
      material that gets detected by ethidium bromide staining method by the comet
      assay protocol. The objective of this study was to compare efficacy of comet
      assay with different assay used to study phage mediated bacterial lysis. The
      assay was performed on culture isolates (N=80 studies), modified comet assay
      appear to have relatively higher sensitivity and specificity than other assay.
      The results of the study showed that the application of comet assay can be an
      economical, time saving and less laborious alternative to conventional plaque
      assay for the detection of bacteriophage mediated bacterial cell lysis. 

PMID- 24681054
TI  - PAPNC, a novel method to calculate nucleotide diversity from large scale next
      generation sequencing data.
AB  - Estimating viral diversity in infected patients can provide insight into pathogen
      evolution and emergence of drug resistance. With the widespread adoption of deep
      sequencing, it is important to develop tools to accurately calculate population
      diversity from very large datasets. Current methods for estimating diversity that
      are based on multiple alignments are not practical to apply to such data. In this
      study, the authors report a novel method (Pairwise Alignment Positional
      Nucleotide Counting, PAPNC) for estimating population diversity from 454 sequence
      data. The diversity measurements determined using this method were comparable to
      those calculated by average pairwise difference (APD) of multiply aligned
      sequences using MEGA5. Diversities were estimated for 9 patient plasma HIV
      samples sequenced with Titanium 454 technology and by single-genome sequencing
      (SGS). Diversities calculated from deep sequencing using PAPNC ranged from 0.002
      to 0.021 while APD measurements calculated from SGS data ranged proximately from
      0.001 to 0.018, with the difference being attributable to PCR error (contributing
      background diversity of 0.0016 in a control sample). Comparison of APDs estimated
      from 100 sets of sequences drawn at random from 454 generated data and from
      corresponding SGS data showed very close correlation between the two methods with
      R(2) of 0.96, and differing on average by about 1% (after correction for PCR
      error). The authors have developed a novel method that is good for calculating
      genetic diversities for large scale datasets from next generation sequencing. It
      can be implemented easily as a function in available variation calling programs
      like SAMtools or haplotype reconstruction software for nucleotide genetic
      diversity calculation. A Perl script implementing this method is available upon
      request. 

PMID- 24681055
TI  - Effect of troxerutin on synaptic plasticity of hippocampal dentate gyrus neurons
      in a beta-amyloid model of Alzheimer's disease: an electrophysiological study.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with a progressive
      cognitive decline and memory loss. Multiple pathogenetic factors including
      aggregated beta-amyloid (Abeta), neurofibrillary tangles (NFTs), cholinergic
      dysfunction and oxidative stress are involved in AD. Abeta, a major constituent
      of the senile plaques, is a potent neurotoxic peptide and has a pivotal role in
      cognitive deficit and reduced synaptic plasticity in AD. In the present study we
      examined the protective effect of troxerutin, as a multipotent bioflavonoid, on
      Abeta (1-42)-induced impairment of evoked field potential in hippocampal DG
      neurons. Male Wistar rats were divided into four groups including Abeta (42-1),
      Abeta (1-42), Abeta (1-42) plus troxerutin and Abeta (42-1) plus troxerutin
      groups. Abeta was injected intracerebroventricularly (i.c.v.) into right lateral
      ventricle and after two weeks the evoked field potential recorded from perforant
      path-DG synapses to assess paired pulse paradigm and long term potentiation
      (LTP). Administration of Abeta (1-42) drastically attenuated the LTP of DG
      neurons, while there was no significant difference in evoked field potentials
      between Abeta (1-42) plus troxerutin group with respect to Abeta (42-1) group.
      This study revealed that troxerutin improves the synaptic failure induced by
      Abeta peptide and can be introduced as a promising multi-potent pharmacological
      agent in prevention or treatment of AD in the future. 

PMID- 24681056
TI  - The role of the sympathetic nervous system in the resuscitative effect of
      stimulating the central serotonin 1A receptors in haemorrhagic shock in rats.
AB  - Haemorrhagic shock is a life threatening condition, and, as such, it is important
      to understand the mechanisms taking part in its reversal. In the 1990s, it was
      shown that activation of serotonin 1A receptors is responsible for the
      circulatory decompensation and development of the sympathoinhibitory phase. In
      previous reports, it was demonstrated that activation of serotonin 1A receptors
      induces resuscitative effects in haemorrhaged rats. However, the effectory
      mechanisms still require further investigation. The aim of the present study was
      to determine whether the sympathetic nervous system participates in the effects
      of serotonin through central serotonin 1A receptors in haemorrhagic shock in
      rats. In order to determine the role of the sympathetic nervous system alpha-1-,
      alpha-2-, and beta-adrenergic receptor agonists - prazosin, yohimbine and
      propranolol, respectively, were used. We found that stimulation of the central
      serotonin 1A receptors by the administration of a selective agonist - 8-hydroxy-2
      (di-n-propylamino)tetralin, 1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (8-OH
      DPAT) into the lateral brain ventricle is connected with the activation of
      compensation mechanisms leading to the increase in the heart rate and blood
      pressure. The current results demonstrate that the stimulation of peripheral
      alpha-1-, alpha-2- and beta-adrenergic receptors plays an essential role in the
      resuscitative effect triggered by the stimulation of central serotonin 1A
      receptors. 

PMID- 24681057
TI  - Pharmacodynamics of potassium channel openers in cultured neuronal networks.
AB  - A novel class of drugs - potassium (K(+)) channel openers or activators - has
      recently been shown to cause anticonvulsive and neuroprotective effects by
      activating hyperpolarizing K(+) currents, and therefore, may show efficacy for
      treating tinnitus. This study presents measurements of the modulatory effects of
      four K(+) channel openers on the spontaneous activity and action potential
      waveforms of neuronal networks. The networks were derived from mouse embryonic
      auditory cortices and grown on microelectrode arrays. Pentylenetetrazol was used
      to create hyperactivity states in the neuronal networks as a first approximation
      for mimicking tinnitus or tinnitus-like activity. We then compared the
      pharmacodynamics of the four channel activators, retigabine and flupirtine
      (voltage-gated K(+) channel KV7 activators), NS1619 and isopimaric acid ("big
      potassium" BK channel activators). The EC50 of retigabine, flupirtine, NS1619,
      and isopimaric acid were 8.0, 4.0, 5.8, and 7.8uM, respectively. The reduction of
      hyperactivity compared to the reference activity was significant. The present
      results highlight the notion of re-purposing the K(+) channel activators for
      reducing hyperactivity of spontaneously active auditory networks, serving as a
      platform for these drugs to show efficacy toward target identification,
      prevention, as well as treatment of tinnitus. 

PMID- 24681058
TI  - Triple therapy with non-biologic DMARDs for rheumatoid arthritis or biologic
      therapy. Is it the same?

PMID- 24681059
TI  - Increased mitochondrial fission and neuronal dysfunction in Huntington's disease:
      implications for molecular inhibitors of excessive mitochondrial fission.
AB  - Huntington's disease (HD) is a fatal, progressive neurodegenerative disease with
      an autosomal dominant inheritance, characterized by chorea, involuntary movements
      of the limbs and cognitive impairments. Since identification of the HD gene in
      1993, tremendous progress has been made in identifying underlying mechanisms
      involved in HD pathogenesis and progression, and in developing and testing
      molecular therapeutic targets, using cell and animal models of HD. Recent studies
      have found that mutant Huntingtin (mHtt) interacts with Dynamin-related protein 1
      (Drp1), causing excessive fragmentation of mitochondria, leading to abnormal
      mitochondrial dynamics and neuronal damage in HD-affected neurons. Some progress
      has been made in developing molecules that can reduce excessive mitochondrial
      fission while maintaining both the normal balance between mitochondrial fusion
      and fission, and normal mitochondrial function in diseases in which excessive
      mitochondrial fission has been implicated. In this article, we highlight
      investigations that are determining the involvement of excessive mitochondrial
      fission in HD pathogenesis, and that are developing inhibitors of excessive
      mitochondrial fission for potential therapeutic applications. 

PMID- 24681060
TI  - Regeneration of stalled immune responses to transformed and infected cells using
      gammadelta T cells.
AB  - Manipulation of the human immune system is becoming more of a therapeutic focus
      as a treatment option or complement. Prominent examples are the increasing use of
      monoclonal antibodies in combating malignant tumours, and the numerous adoptive
      immunotherapy trials underway. One important aspect of any use of the human
      immune system in this regard is to harness the power of professional antigen
      presenting cells (pAPC), that is, dendritic cells (DC), to direct immune
      responses. Here, we review how recent findings regarding the biology of
      gammadeltaT cells have revealed that they, surprisingly, could serve as
      convenient tools for this purpose, in that they combine innate cytotoxic cell and
      pAPC functions in one cell type, with potential benefits in cancer immunotherapy
      and infectious disease. 

PMID- 24681061
TI  - Office diagnostic and operative hysteroscopy using local anesthesia only: an
      analysis of patient reported pain and other procedural outcomes.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of a multimodality local
      anesthetic protocol for office diagnostic and operative hysteroscopy. DESIGN:
      Retrospective cohort study (Canadian Task Force classification II-3). SETTING:
      Academic community-based institution. PATIENTS: Five hundred sixty-nine women
      undergoing 639 office-based diagnostic or operative hysteroscopic procedures.
      INTERVENTIONS: Multimodality local anesthetic protocol addressing vagina, cervix,
      paracervical region, and endometrial cavity. MEASUREMENTS AND MAIN RESULTS:
      Primary outcomes were numeric pain scores and rate of premature termination
      because of pain. Secondary outcomes included procedure pain and parity, delivery
      route, menopausal status, procedure type, and cost effect on procedure delivery.
      The overall mean (SD) pain score across 535 evaluable procedures was 3.7 (2.5).
      Patients undergoing operative hysteroscopy had a higher mean maximum pain score
      than did those who underwent diagnostic hysteroscopy only (4.1 vs 3.2; p < .001).
      There was no difference among women in different age groups; however, those with
      both cesarean section and vaginal delivery had scores higher than the mean (4.7
      [0.4]; p < .001). The estimated cost savings was almost $2 million. CONCLUSION:
      Using a multimodality approach to local anesthesia, a broad spectrum of
      diagnostic and operative procedures can be performed successfully, comfortably,
      and inexpensively in the context of an office procedure room, without the need
      for procedural sedation.

PMID- 24681062
TI  - Compared with cystectomy, is ovarian vaporization of endometriotic cysts truly
      more effective in maintaining ovarian reserve?
AB  - STUDY OBJECTIVE: To evaluate how endometriotic cystectomy and vaporization affect
      ovarian reserve after conservative surgery. DESIGN: Prospective study (Canadian
      Task Force classification II-1). SETTING: Hokusetsu General Hospital. PATIENTS:
      Ninety-nine women who underwent conservative surgery to treat endometriotic cysts
      from June 2011 to July 2013. INTERVENTIONS: Vaporization with bipolar current was
      performed in nulligravid women, and cystectomy in those who had a child. In women
      with endometriotic cysts, bilateral cystectomy was performed in 28, bilateral
      vaporization in 15, unilateral cystectomy in 40, and unilateral vaporization in
      16. In all patients, preoperative and postoperative serum anti-mullerian hormone
      (AMH) and follicle-stimulating hormone (FSH) concentrations at the early
      proliferative phase were assayed, and the change in concentrations was evaluated
      for each operation. MEASUREMENT AND MAIN RESULTS: In the bilateral cystectomy
      group, the mean (SD) postoperative FSH concentration (19.3 [21.8] IU/mL) was
      statistically higher than the preoperative concentration (9.0 [6.2] IU/mL) (p <
      .01). AMH significantly declined after all operations to treat endometriotic
      cysts, and the rate of decline in the AMH concentration was >50% compared with
      preoperative concentrations. CONCLUSION: Whether endometriotic cysts are
      unilateral or bilateral, both cystectomy and vaporization using bipolar current
      can lower ovarian reserve. Therefore, it is necessary to develop more effective
      surgical procedures to prevent ovarian damage.

PMID- 24681063
TI  - Hysterectomy by transvaginal natural orifice transluminal endoscopic surgery
      (NOTES): a series of 137 patients.
AB  - STUDY OBJECTIVE: To evaluate the feasibility and safety of hysterectomy in benign
      disease using transvaginal natural orifice transluminal endoscopic surgery
      (NOTES). DESIGN: Prospective observational study (Canadian Task Force
      classification II-3). SETTING: Tertiary referral medical center. PATIENTS: From
      May 2010 to August 2011, consecutive patients who were scheduled to undergo
      laparoscopic hysterectomy and without virginity or suspected pelvic inflammation
      or cul-de-sac obliteration were included. INTERVENTION: Total hysterectomy via
      transvaginal NOTES. MEASUREMENTS AND MAIN RESULTS: The study included 137
      patients, with mean (SEM) age 46.0 (0.4) years and body mass index 24.7 (0.4).
      Transvaginal NOTES was successfully performed in 130 patients (94.9%). Fifteen
      patients underwent concurrent adhesiolysis, and 17 underwent adnexal procedures.
      Mean (SEM) uterine weight was 450.0 (24.1) g; in 45 patients (34.6%), uterine
      weight was >500 g, and in 7 (5.4%) it was >1000 g. Operative time was 88.2 (4.1)
      minutes, with blood loss of 257.7 (23.9) mL. In 2 patients there was
      intraoperative hemorrhage or unintended cystotomy, and in another 5 transvaginal
      colpotomy failed because of a narrow vagina, cul-de-sac obliteration by bowel
      adhesions, or mass obstruction. Complications in these 7 patients (5.1%) were
      successfully managed via transabdominal laparoscopy. Five patients (3.6%)
      experienced postoperative urinary retention or febrile morbidity, and recovered
      uneventfully with conservative treatment. CONCLUSION: Transvaginal NOTES is a
      feasible technique for performance of hysterectomy and can be used in procedures
      that are difficult to complete via conventional vaginal surgery because posterior
      colpotomy is achievable. This procedure was not impeded by uterine volume, and
      had the advantage of no abdominal incision.

PMID- 24681064
TI  - Light-guided hysteroscopic resection of complete septate uterus with preservation
      of duplicated cervix.
AB  - The objective of the present study, performed at a tertiary university hospital,
      was to propose a novel method of hysteroscopic resection of complete septate
      uterus with preservation of duplicated cervix. The retrospective study included 5
      women with complete septate uterus and cervical duplication and who also
      experienced infertility with or without pregnancy loss. All patients underwent
      bougie-guided or light-guided hysteroscopic perforation of the uterine septum
      above the endocervix, followed by septum resection. The success rate of complete
      uterine septum perforation under bougie guidance was 60% (3 of 5 procedures), and
      of light guidance was 100% (2 procedures). After hysteroscopic septum resection,
      2 of 5 women achieved pregnancy within 3 months and delivered uneventfully at
      term. It is concluded that light guidance is superior to bougie guidance for
      hysteroscopic perforation of complete septate uterus with preservation of the
      duplicated cervix.

PMID- 24681065
TI  - Recurrent postmenopausal bleeding: a prospective cohort study.
AB  - STUDY OBJECTIVE: To estimate the prevalence of genital tract diseases in women
      with initial and recurrent postmenopausal bleeding (PMB) to help inform
      diagnostic pathways. DESIGN: Prospective cohort study (Canadian Task Force
      classification: II-2). SETTING: Large urban teaching hospital. PATIENTS: Of 1938
      consecutive women with postmenopausal bleeding, 106 (5%) were investigated for a
      recurrent episode after having normal findings of previous investigations.
      INTERVENTIONS: All women underwent pelvic examination and ultrasound scanning. An
      endometrial biopsy was performed when endometrial thickness was >4 mm in women
      with a first episode of PMB, with recourse to outpatient hysteroscopy after
      correlation between clinical and pathologic findings. All women with a recurrent
      PMB episode underwent endometrial biopsy and outpatient hysteroscopy.
      MEASUREMENTS AND MAIN RESULTS: The risk of having endometrial cancer or
      hyperplasia with atypia was significantly less in women with recurrent PMB (9%)
      as compared with those with a first episode of PMB (8%) (p = .002), but were
      significantly more likely to have benign endometrial polyps (28%) compared with
      women with a first episode of PMB (19%) (relative risk, 1.47; 95% confidence
      interval, 1.07-2.02; p = .02). CONCLUSION: Recurrent PMB results in less
      likelihood of premalignant and malignant endometrial disease; however, in 1 of 4
      women PMB is caused by endometrial polyps. First-line investigation in women with
      recurrent PMB should be tests that have high accuracy for enabling diagnosis of
      focal diseases, such as outpatient hysteroscopy or saline infusion sonography.

PMID- 24681066
TI  - Design, synthesis and bioevaluation of N-trisubstituted pyrimidine derivatives as
      potent aurora A kinase inhibitors.
AB  - The design and synthesis of a new series of N-trisubstituted (at C2, C4 and C6
      respectively) pyrimidine derivatives were reported, their in vitro structure
      activity relationships vs. aurora A kinase were also discussed. Our results
      demonstrated that the introduction of characteristic N-substituted side chain at
      C2 of pyrimidines possessed a potent aurora A inhibitory activity, the position
      and the nature of the substituents on the phenyl ring of aniline side chain
      played key roles in cellular kinase inhibitory potency. Most tested compounds
      exhibited good inhibitory activities against aurora A kinase and various human
      tumor cell lines. Compounds 7j, 7m-n and 7p showed strong growth-inhibitory
      activities in the solid CNE-2 tumor cell and selectively blocked cell-cycle
      progression at the G2/M phase. 

PMID- 24681067
TI  - Synthesis and biological evaluation of N-dehydrodipeptidyl-N,N'-dicyclohexylurea
      analogs.
AB  - Some N-[(N-benzoyldehydrophenylalalnyl)glycinyl/cysteinyl]-N,N'-dicyclohexylurea
      analogs (3a-3o) were synthesized by conjugating different substituted N
      benzoyldehydrophenylalanyl glycines/cysteines (differing substitutions on
      benzylidene ring) and dicyclohexyl carbodiimide (DCC) using base as a catalyst.
      The synthesized compounds were characterized and evaluated for biological
      activities. Compounds 3a and 3h with unsubstituted dehydrophenylalanyl
      glycinyl/cysteinyl moiety exhibited moderate anti-inflammatory and analgesic
      activities. Compound 3j bearing 4-hydroxy substitution on benzylidene ring of
      dehydrophenylalanyl cysteinyl moiety displayed potent antimicrobial and
      antioxidant activities. The results obtained from docking studies on compound 3j
      with penicillin binding protein and protease supported the results. 

PMID- 24681068
TI  - Synthesis, structure-activity relationships, and in vitro antibacterial and
      antifungal activity evaluations of novel pyrazole carboxylic and dicarboxylic
      acid derivatives.
AB  - A series of pyrazole-3-carboxylic acid and pyrazole-3,4-dicarboxylic acid
      derivatives were synthesized, the structures were confirmed by their NMR ((1)H
      and (13)C) and FT-IR spectra, and elemental analyses. The antibacterial and
      antifungal activities of the compounds against five bacterial and five fungal
      pathogens were screened using modified agar well diffusion assay. Most of the
      molecules have inhibitory effects on both standard and clinical Candida albicans
      strains. However, only the molecules 8, 10, 21, and 22 demonstrate some
      inhibitory effects on Candida parapsilosis, Candida tropicalis, and Candida
      glabrata strains. The structure-antifungal activity relationships of the
      compounds on the C. albicans strains were investigated by electron-conformational
      method. The pharmacophores and antipharmacophores responsible for the inhibition
      and non-inhibition of the C. albicans strains were obtained by electronic and
      geometrical characteristics of the reactive fragments of the molecules. These
      fragments along with the associated parameters can be used in designing the
      future more potent antifungal agents. It has been shown that both the positions
      of electronegative atoms like F and O in the pyrazole substituents and the amount
      of the associated charges on such atoms are crucial in regulating the strength of
      antifungal activity for the C. albicans strain. 

PMID- 24681069
TI  - Therapeutic potential of leptin receptor modulators.
AB  - Leptin, a pleiotropic molecule mainly produced by adipose tissue, was first
      discovered as a hormone controlling body weight and energy expenditure. In
      addition, leptin can modulate several processes in peripheral tissues such as
      immune response, fertility, hematopoiesis and carcinogenesis. The development of
      molecules that block or stimulate leptin receptor may therefore serve as a potent
      tool for studying the role of leptin in mammalian physiology and pathology, but
      it also may open new possibilities for therapy. This article presents an overview
      of current knowledge on leptin receptor modulators focusing on leptin mutein,
      leptin peptide modulators as well as small molecules with heterocyclic structure.

PMID- 24681070
TI  - Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as
      cholinesterase inhibitors.
AB  - Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently
      synthesized starting from saccharin sodium salt. Pyrazolo[4,3
      c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde,
      followed by the incorporation of a benzimidazole or similar ring systems by
      treatment with arylenediamines. These phenylene-connected hybrid compounds were
      investigated as potential inhibitors of acetylcholinesterase (AChE) and
      butyrylcholinesterase (BuChE). Compounds 12d and 12k were the most potent AChE
      inhibitors with IC50 values of 11 and 13 nM, respectively, while 6j (IC50 = 17
      nM) proved to be the most active inhibitor against BuChE with remarkable
      selectivity for BuChE over AChE. Molecular docking studies were also performed on
      human AChE and BuChE to suggest possible binding modes in which the inhibitor's
      extended structure is accommodated along the active site gorge of both enzymes.

PMID- 24681071
TI  - A cycling workstation to facilitate physical activity in office settings.
AB  - Facilitating physical activity during the workday may help desk-bound workers
      reduce risks associated with sedentary behavior. We 1) evaluated the efficacy of
      a cycling workstation to increase energy expenditure while performing a typing
      task and 2) fabricated a power measurement system to determine the accuracy and
      reliability of an exercise cycle. Ten individuals performed 10 min trials of
      sitting while typing (SIT type) and pedaling while typing (PED type). Expired
      gases were recorded and typing performance was assessed. Metabolic cost during
      PED type was ~ 2.5 * greater compared to SIT type (255 +/- 14 vs. 100 +/- 11 kcal
      h(-1), P < 0.01). Typing time and number of typing errors did not differ between
      PED type and SIT type (7.7 +/- 1.5 vs. 7.6 +/- 1.6 min, P = 0.51, 3.3 +/- 4.6 vs.
      3.8 +/- 2.7 errors, P = 0.80). The exercise cycle overestimated power by 14-138%
      compared to actual power but actual power was reliable (r = 0.998, P < 0.01). A
      cycling workstation can facilitate physical activity without compromising typing
      performance. The exercise cycle's inaccuracy could be misleading to users.

PMID- 24681072
TI  - Police officer in-vehicle discomfort: appointments carriage method and vehicle
      seat features.
AB  - Musculoskeletal pain is commonly reported by police officers. A potential cause
      of officer discomfort is a mismatch between vehicle seats and the method used for
      carrying appointments. Twenty-five police officers rated their discomfort while
      seated in: (1) a standard police vehicle seat, and (2) a vehicle seat custom
      designed for police use. Discomfort was recorded in both seats while wearing
      police appointments on: (1) a traditional appointments belt, and (2) a load
      bearing vest/belt combination (LBV). Sitting in the standard vehicle seat and
      carrying appointments on a traditional appointments belt were both associated
      with significantly elevated discomfort. Four vehicle seat features were most
      implicated as contributing to discomfort: back rest bolster prominence; lumbar
      region support; seat cushion width; and seat cushion bolster depth. Authorising
      the carriage of appointments using a LBV is a lower cost solution with potential
      to reduce officer discomfort. Furthermore, the introduction of custom-designed
      vehicle seats should be considered. 

PMID- 24681074
TI  - Factors associated with readmissions and outcomes of patients hospitalized for
      inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBD) are
      hospitalized frequently. We sought to identify factors associated with risk for
      IBD-related readmission to the hospital. METHODS: We performed a retrospective
      analysis of 26,403 patients hospitalized for IBD from 2004 through 2010 using the
      Canadian Institute for Health Information Discharge Abstract databases. We
      examined whether demographic factors, comorbidity, and hospital IBD admission
      volume were associated with readmission rates, length of stay, bowel resection,
      and mortality. RESULTS: Young, middle-age, and elderly adults were more than
      twice as likely to undergo surgery during hospitalization than pediatric
      patients. Elderly patients with IBD had a nearly 40-fold greater in-hospital
      mortality than pediatric patients (odds ratio, 37.4; 95% confidence interval
      [CI], 5.17-270.0). In-hospital mortality was lower at hospitals with the highest
      volume of IBD patients than at those with low volume (odds ratio, 0.20; 95% CI,
      0.05-0.97). Rates of readmission were lower for patients with ulcerative colitis
      than Crohn's disease (hazard ratio, 0.79; 95% CI, 0.72-0.86). The hazard ratios
      for readmission among young, middle-age, and elderly adults, compared with those
      of pediatric patients, were 0.79 (95% CI, 0.69-0.90), 0.57 (95% CI, 0.49-0.65),
      and 0.44 (95% CI, 0.37-0.53), respectively. Rates of readmission were lower at
      the highest-volume, compared with the lowest-volume, hospitals (hazard ratio,
      0.78; 95% CI, 0.64-0.96). CONCLUSIONS: Based on a retrospective database
      analysis, pediatric patients with IBD are at greater risk for readmission to the
      hospital than older patients. Efforts should be made to determine whether factors
      that contribute to this risk are preventable. The lower risk of readmission at
      the highest-volume hospitals may reflect optimal management during
      hospitalization or follow-up evaluation.

PMID- 24681073
TI  - Preference of endoscopic ablation over medical prevention of esophageal
      adenocarcinoma by patients with Barrett's esophagus.
AB  - BACKGROUND & AIMS: Endoscopic intervention or pharmacologic inhibition of
      cyclooxygenase might be used to prevent progression of Barrett's esophagus (BE)
      to esophageal adenocarcinoma (EAC). We investigated whether patients with BE
      prefer endoscopic therapy or chemoprevention of EAC. METHODS: Eighty-one subjects
      with nondysplastic BE were given a survey that described 2 scenarios. The survey
      explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by
      50%, with 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced
      lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased
      the risk for ulcer by 75%. Subjects indicated their willingness to undergo either
      treatment A and/or treatment B if endoscopic surveillance were required every 3-5
      years, every 10 years, or were not required. Visual aids were included to
      represent risk and benefit percentages. RESULTS: When surveillance was required
      every 3-5 years, more subjects were willing to undergo treatment A than treatment
      B (78%, 63 of 81 vs 53%, 43 of 81; P < .01). There were no differences in age,
      sex, education level, or history of cancer, heart disease, or ulcer between
      patients willing to undergo treatment A and those willing to undergo treatment B.
      Altering the frequency of surveillance did not affect patients' willingness to
      undergo either treatment. CONCLUSIONS: In a simulated scenario, patients with BE
      preferred endoscopic intervention over chemoprevention for EAC. Further
      investigation of the shared decision-making process regarding preventive
      strategies for patients with BE may be warranted.

PMID- 24681075
TI  - Characterization of corticobulbar pharyngeal neurophysiology in dysphagic
      patients with Parkinson's disease.
AB  - BACKGROUND & AIMS: Dysphagia in patients with Parkinson's disease, persisting
      despite dopaminergic treatment, affects intake of nutrients and medication, and
      reduces quality of life (QOL). We investigated the neurophysiologic mechanisms
      that contribute to dysphagia in these patients, on and off L-3,4
      dihydroxyphenylalanine (levodopa), using transcranial magnetic stimulation.
      METHODS: We studied 26 patients with Parkinson's disease (age, 65 +/- 9 y; 10
      men). Dysphagia and QOL were first assessed with qualitative questionnaires.
      Twelve hours after patients were taken off levodopa, they underwent cortical
      transcranial magnetic stimulation mapping of the pharyngeal musculature and
      trigeminal (bulbar) transcranial magnetic stimulation, as well as
      videofluoroscopy to examine swallowing. The analyses were repeated after
      administration of levodopa. RESULTS: Eleven patients initially reported dysphagia
      and reduced QOL scores. Videofluoroscopy identified 10 patients with swallowing
      impairments on and off levodopa, and 6 patients with swallowing impairments only
      on levodopa; the remaining 10 subjects showed no swallowing impairments, on or
      off the drug. While patients were on levodopa, those with swallowing impairments
      had bilateral increases in pharyngeal cortical excitability compared with those
      with no swallowing impairment (P < .05). By contrast, with medication, amplitudes
      of brainstem reflexes were altered only in patients with swallowing impairments
      on levodopa; these were decreased compared with when the patients were off
      levodopa. CONCLUSIONS: In patients with Parkinson's disease, dopaminergic
      medications such as levodopa can negatively affect swallowing. The increased
      cortical excitability observed in dysphagic patients after they begin taking
      levodopa likely results from compensatory mechanisms, perhaps secondary to
      subcortical disease, because we observed associated inhibition of brainstem
      reflexes in patients with affected swallowing on medication. UK clinical trials
      registration no., 9882.

PMID- 24681076
TI  - Measures of adiposity are associated with increased risk of peptic ulcer.
AB  - BACKGROUND & AIMS: Obesity is associated with systemic inflammation, alterations
      in the intestinal microbiome, and decreased epithelial integrity. The association
      between obesity and peptic ulcer has not been investigated thoroughly. METHODS:
      We conducted a prospective cohort study of 47,120 men enrolled in the Health
      Professionals Follow-Up Study (mean age at baseline, 54 y). Biennially, we
      updated information on body mass index (BMI), physical activity, smoking, and use
      of nonsteroidal anti-inflammatory drugs or aspirin. Self-reported waist and hip
      measurements were validated among a subsample of participants. Self-reported
      cases of gastric and duodenal ulcers were confirmed by medical record review.
      Helicobacter pylori status was determined from endoscopic biopsy specimens, serum
      antibody measurements, and/or stool antigen assays documented in the medical
      record. We used Cox proportional hazards modeling to calculate hazard ratios and
      95% confidence intervals (CIs). RESULTS: We documented 272 gastric and 320
      duodenal ulcers over 24 years of follow-up evaluation. The multivariate-adjusted
      hazard ratio for gastric ulcer was 1.83 (95% CI, 1.20-2.78; P(trend) < .01) for
      obese men (BMI, >=30.0 kg/m(2)), compared with men with BMIs of 23.0 to 24.9
      kg/m(2), and 1.88 (95% CI, 1.06-3.33; P(trend) = .04) for men with waist-to-hip
      ratios (WHR) of 1.00 or higher, compared with men with a WHR of 0.85 to 0.89. The
      risk of duodenal ulcer was not associated with BMI (P(trend) = .24) or WHR
      (P(trend) = .68). In secondary analyses, increased BMI and WHR each were
      associated with increased risk of H pylori-negative, but not H pylori-positive,
      ulcers. The effect of BMI on ulcer risk did not change with use of aspirin or
      nonsteroidal anti-inflammatory drugs, alcohol consumption, physical activity, or
      smoking. CONCLUSIONS: In a large prospective cohort of male health professionals,
      central and total obesity were associated with increased risk of peptic ulcer
      particularly gastric and H pylori-negative ulcers.

PMID- 24681077
TI  - Allium vegetables and garlic supplements do not reduce risk of colorectal cancer,
      based on meta-analysis of prospective studies.
AB  - BACKGROUND & AIMS: Laboratory studies have provided evidence that allium
      vegetables and garlic supplements might protect against colorectal cancer (CRC),
      but epidemiologic studies have produced inconsistent findings. METHODS: We
      conducted a meta-analysis of prospective studies evaluating the associations
      between allium vegetables, garlic supplements, and CRC risk. We pooled effect
      measures using fixed- or random-effect models, assessing the highest vs the
      lowest intakes. We used a dose-response regression model to evaluate the
      relationship between allium vegetable intake and CRC risk. RESULTS: Our analysis
      included 8 studies with 20 reports of the effects of allium vegetables (5458
      patients with CRC including 7,125,067 person-years) and 5 studies with 11 reports
      of the effects of garlic supplements (2685 patients with CRC including 2,304,439
      person-years). We found no association between higher intake of allium vegetables
      and CRC risk (relative risk [RR], 1.06; 95% confidence interval [CI], 0.96-1.17;
      P = .26). Intake of allium vegetables did not correspond to CRC risk (P for
      nonlinear = .24, P for linear = .20). In subgroup analysis, a higher consumption
      of allium vegetables was associated marginally with increased risk of colon
      cancer among women (RR, 1.23; 95% CI, 1.01-1.50; P = .05). Use of garlic
      supplements was associated significantly with an increased risk of CRC (RR, 1.18;
      95% CI, 1.02-1.36; P = .03). CONCLUSIONS: In a meta-analysis, we found no
      evidence that higher intake of allium vegetables reduced the risk for CRC. We
      observed that garlic supplements increased the risk for CRC, but this finding
      requires external validation.

PMID- 24681079
TI  - Risk of Clostridium difficile infection in hospitalized patients receiving
      metronidazole for a non-C difficile infection.
AB  - BACKGROUND & AIMS: Antibiotics often are given to prevent infections but also
      constitute a risk factor for Clostridium difficile infection (CDI). Metronidazole
      is an effective treatment for CDI. We investigated whether prophylactic
      administration of metronidazole to patients before they receive other antibiotics
      reduces the risk of CDI. METHODS: We performed a retrospective cohort analysis of
      data collected from 12,026 high-risk patients admitted to Cleveland Clinic
      Foundation Hospitals from 2008 through 2012. High-risk patients were defined as
      age 55 or older who received a broad-spectrum antibiotic (piperacillin-tazobactam
      or ciprofloxacin) and a gastric acid suppressant (a proton pump inhibitor or a
      histamine-2 receptor blocker) during their hospitalization. Development of CDI
      was compared between patients who received metronidazole for non-CDI indications
      before broad-spectrum antibiotics (n = 811) and those who did not (n = 11,215).
      Logistic regression was used to control for patient demographics and
      comorbidities. RESULTS: The rate of CDI was 1.4% (n = 11) among the patients who
      received metronidazole for non-CDI indications and 6.5% (n = 728) among those who
      did not. This was observed to be an 80% reduction in CDI among patients who
      received metronidazole (odds ratio, 0.21; 95% confidence interval, 0.11-0.38; P <
      .001), adjusted for age, sex, and comorbidities. CONCLUSIONS: Based on a
      retrospective analysis, metronidazole might be used to prevent CDI in certain
      high-risk patients. Prospective controlled trials are necessary before making
      further recommendations.

PMID- 24681080
TI  - Effects of topical steroids on tight junction proteins and spongiosis in
      esophageal epithelia of patients with eosinophilic esophagitis.
AB  - BACKGROUND & AIMS: The allergic response associated with eosinophilic esophagitis
      (EoE) occurs when food antigens permeate tight junction-mediated epithelial
      dilated intercellular spaces. We assessed whether levels of tight junction
      proteins correlate with the dilation of intercellular spaces (spongiosis) and the
      effects of topical steroids on these parameters. METHODS: We assessed esophageal
      biopsy samples from 10 patients with active EoE treated with topical fluticasone,
      10 untreated patients, and 10 patients without esophageal disease (controls) for
      degree of spongiosis. Immunohistochemical assays were used to determine the
      levels of the tight junction proteins filaggrin, zonula occludens (ZO)-1, ZO-2,
      ZO-3, and claudin-1. Histology and immunohistochemistry results were assessed
      blindly, with levels of tight junction proteins and degree of spongiosis rated on
      scales of 0 to 3. RESULTS: The mean degrees of spongiosis in untreated and
      treated patients with EoE were 1.3 and 0.4, respectively (P = .016). Esophageal
      epithelia did not stain significantly for ZO-1 or ZO-2. Filaggrin was observed in
      a predominant cytoplasmic pattern, compared with the cytoplasmic and membranous
      patterns of ZO-3 and claudin-1. In biopsy specimens from patients with active
      EoE, the mean staining intensities for filaggrin, ZO-3, and claudin-1 were 1.6,
      1.4, and 0.7, respectively. In biopsy specimens from patients treated with
      fluticasone, levels of filaggrin, ZO-3, and claudin-1 were 2.8 (P = .002 compared
      with untreated patients), 1.7 (P = .46 compared with untreated patients), and 1.3
      (P = .25 compared with untreated patients), respectively. The correlation between
      the level of filaggrin and the degree of spongiosis was r = 0.23, and between ZO
      3 staining and the degree of spongiosis was r = .016 (P = .001 for filaggrin vs
      ZO-3 staining). CONCLUSIONS: Filaggrin, ZO-3, and claudin-1 (but not ZO-1 or ZO
      2) are detected in the esophageal mucosa of patients with EoE treated with
      steroids and individuals without esophageal disease. Without treatment,
      spongiosis increases, corresponding with reduced levels of filaggrin, ZO-3, and
      claudin-1. Loss of tight junction regulators and dilation of intercellular spaces
      appear to be involved in the pathophysiology of EoE and could be targets for
      treatment.

PMID- 24681081
TI  - Effects of Clostridium difficile infection in patients with alcoholic hepatitis.
AB  - BACKGROUND & AIMS: Infection increases mortality in patients with alcoholic
      hepatitis (AH). Little is known about the association between Clostridium
      difficile infection (CDI) and AH. We examined the prevalence and effects of CDI
      in patients with AH, compared with those of other infections. METHODS: We
      performed a cross-sectional analysis using data collected from the Nationwide
      Inpatient Sample, from 2008 through 2011. International Classification of
      Diseases, 9th revision, Clinical Modification codes were used to identify
      patients with AH. We used multivariable logistic regression to determine risk
      factors that affect mortality, negative binomial regression to evaluate the
      effects of CDI on predicted length of stay (LOS), and Poisson regression to
      determine the effects of CDI on predicted hospital charges. Chi-square and
      Wilcoxon rank-sum analyses were used to compare mortality, LOS, and hospital
      charges associated with CDI with those associated with urinary tract infection
      (UTI) and spontaneous bacterial peritonitis (SBP). RESULTS: Of 10,939 patients
      with AH, 177 had CDI (1.62%). Patients with AH and CDI had increased odds of
      inpatient mortality (adjusted odds ratio, 1.75; P = .04), a longer predicted LOS
      (10.63 vs 5.75 d; P < .001), and greater predicted hospital charges ($36,924.30
      vs $29,136.58; P < .001), compared with those without CDI. Compared with UTI, CDI
      was associated with similar mortality but greater LOS (9 vs 6 d; P < .001) and
      hospital charges ($45,607 vs $32,087; P < .001). SBP was associated with higher
      mortality than CDI (17.3% vs 10.1%; P = .045), but similar LOS and hospital
      charges. CONCLUSIONS: In patients with AH, CDI is associated with greater
      mortality and health care use. These effects appear similar to those for UTI and
      SBP. We propose further studies to determine the cost effectiveness of screening
      for CDI among patients with AH.

PMID- 24681082
TI  - Hemosuccus pancreaticus caused by superior mesenteric artery fistula presenting
      as pancreatic panniculitis and anemia.

PMID- 24681078
TI  - Rate of detection of advanced neoplasms in proximal colon by simulated
      sigmoidoscopy vs fecal immunochemical tests.
AB  - BACKGROUND & AIMS: We compared the ability of biennial fecal immunochemical
      testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced
      neoplasms in a population-based, multicenter, nationwide, randomized controlled
      trial. METHODS: We identified asymptomatic men and women, 50-69 years old,
      through community health registries and randomly assigned them to groups that
      received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield
      was simulated from results obtained from the colonoscopy group, according to the
      criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy
      referral. Patients who underwent FIT and were found to have >=75 ng hemoglobin/mL
      were referred for colonoscopy. Data were analyzed from 5059 subjects in the
      colonoscopy group and 10,507 in the FIT group. The main outcome was rate of
      detection of any advanced neoplasm proximal to the splenic flexure. RESULTS:
      Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy
      simulation group compared with 288 (2.7%) in the FIT group (odds ratio for
      sigmoidoscopy, 2.29; 95% confidence interval, 1.93-2.70; P = .0001).
      Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of
      patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20-3.10; P =
      .0001). The methods did not differ significantly in identifying patients with
      advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78
      1.76; P = .44). This was probably due to the lower performance of both strategies
      in detecting patients with proximal lesions (sigmoidoscopy detected these in
      19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy
      detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy,
      but not FIT, detected proximal lesions in lower percentages of women (especially
      those 50-59 years old) than men. CONCLUSIONS: Sigmoidoscopy and FIT have similar
      limitations in detecting advanced proximal neoplasms, which depend on patients'
      characteristics; sigmoidoscopy underperforms for women 50-59 years old. Screening
      strategies should be designed on the basis of target population to increase
      effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997.

PMID- 24681083
TI  - An unusual cause of abnormal liver enzymes, leukocytosis, and right upper
      quadrant abdominal pain.

PMID- 24681084
TI  - Use of the HAS-BLED bleeding score in real-life settings.

PMID- 24681085
TI  - High shear dependent von Willebrand factor self-assembly fostered by platelet
      interaction and controlled by ADAMTS13.
AB  - INTRODUCTION: The paradigm of activation induced platelet aggregation has
      recently been refuted under blood flow conditions with shear rates exceeding
      20,000s(-1). These lead to reversible rolling platelet aggregates, which were
      dependent on the presence of immobilized and soluble von Willebrand factor.
      MATERIAL AND METHODS: In vitro experiments using direct fluorescence video
      microscopy were performed in wall parallel and stagnation point flow chambers
      with shear rates raised from 20,000 to 50,000s(-1). Washed blood cell suspension
      containing recombinant von Willebrand factor (rVWF) was perfused over rVWF or
      collagen coated surfaces. RESULTS: Here we show for the first time with the
      visualization of rVWF that not only colloid and polymer, i.e. platelets and VWF,
      form a composite, but that VWF itself is capable of entirely reversible self
      assembly. On a collagen surface the platelet-VWF-conglomerates did not roll but
      VWF nets bound permanently to the collagen fibers and captured and immobilized
      platelets from the flow. Lowering the shear rate below the threshold of 20,000s(
      1) no longer dissolved these deposits. Ultralarge multimer containing rVWF was
      most effective compared to normal sized rVWF. The presence of ADAMTS13 limited
      rolling aggregate and platelet-VWF-conglomerate formation to a time window of 7
      8minutes. Changing wall parallel flow to stagnation point flow halved the
      required shear rate threshold. CONCLUSION: We conclude that flow dynamics can
      trigger reversible von Willebrand factor self-assembly and platelet-VWF
      conglomerate accrual, which are regulated by ADAMTS13 to a time span needed by
      coagulation to stabilize it, e.g. in case of vessel injury.

PMID- 24681087
TI  - Potential applications of cryogenic technologies to plant genetic improvement and
      pathogen eradication.
AB  - Rapid increases in human populations provide a great challenge to ensure that
      adequate quantities of food are available. Sustainable development of
      agricultural production by breeding more productive cultivars and by increasing
      the productive potential of existing cultivars can help meet this demand. The
      present paper provides information on the potential uses of cryogenic techniques
      in ensuring food security, including: (1) long-term conservation of a diverse
      germplasm and successful establishment of cryo-banks; (2) maintenance of the
      regenerative ability of embryogenic tissues that are frequently the target for
      genetic transformation; (3) enhancement of genetic transformation and plant
      regeneration of transformed cells, and safe, long-term conservation for
      transgenic materials; (4) production and maintenance of viable protoplasts for
      transformation and somatic hybridization; and (5) efficient production of
      pathogen-free plants. These roles demonstrate that cryogenic technologies offer
      opportunities to ensure food security. 

PMID- 24681086
TI  - Monitoring Keap1-Nrf2 interactions in single live cells.
AB  - The transcription factor NF-E2 p45-related factor 2 (Nrf2) and its negative
      regulator Kelch-like ECH associated protein 1 (Keap1) control the expression of
      nearly 500 genes with diverse cytoprotective functions. Keap1, a substrate
      adaptor protein for Cullin3/Rbx1 ubiquitin ligase, normally continuously targets
      Nrf2 for degradation, but loses this ability in response to electrophiles and
      oxidants (termed inducers). Consequently, Nrf2 accumulates and activates
      transcription of its downstream target genes. Many inducers are phytochemicals,
      and cruciferous vegetables represent one of the richest sources of inducer
      activity among the most commonly used edible plants. Here we summarize the
      discovery of the isothiocyanate sulforaphane as a potent inducer which reacts
      with cysteine sensors of Keap1, leading to activation of Nrf2. We then describe
      the development of a quantitative Forster resonance energy transfer (FRET)-based
      methodology combined with multiphoton fluorescence lifetime imaging microscopy
      (FLIM) to investigate the interactions between Keap1 and Nrf2 in single live
      cells, and the effect of sulforaphane, and other cysteine-reactive inducers, on
      the dynamics of the Keap1-Nrf2 protein complex. We present the experimental
      evidence for the "cyclic sequential attachment and regeneration" or "conformation
      cycling" model of Keap1-mediated Nrf2 degradation. Finally, we discuss the
      implications of this mode of regulation of Nrf2 for achieving a fine balance
      under normal physiological conditions, and the consequences and mechanisms of
      disrupting this balance for tumor biology. 

PMID- 24681089
TI  - Cloning, expression and evaluation of diagnostic potential of recombinant capsid
      protein based IgM ELISA for chikungunya virus.
AB  - The resurgence of chikungunya virus in the form of unprecedented explosive
      epidemic with unusual clinical severity after a gap of 32 years is a point of
      major public health concern. Definitive diagnosis is critical in differentiating
      the disease, especially in dengue endemic areas. The immunoglobulin M (IgM)
      enzyme-linked immunosorbent assay (ELISA) is widely used for diagnosis of
      chikungunya infection. However IgM ELISA based on whole virus antigen is
      associated with biohazard risk. The present study describes the development and
      evaluation of recombinant capsid protein based indirect IgM antibody capture
      micro plate enzyme linked immunosorbent assay (ELISA) for rapid and accurate
      diagnosis of chikungunya infection. The gene coding for capsid protein was cloned
      in frame with GST tag in pET41a+ vector and expressed in E. coli followed by
      purification with affinity chromatography. The comparative evaluation of in-house
      chikungunya IgM ELISA vis-a-vis commercially available SD ELISA kit with 90
      chikungunya suspected acute phase human patient serum samples revealed 97%
      accordance. The overall sensitivity and specificity of the reported capsid
      protein based IgM ELISA was 100% and 95% respectively with 96% PPV and 100% NPV.
      These findings clearly demonstrated the usefulness of the recombinant capsid
      protein based CHIKV IgM ELISA for reliable clinical diagnosis of CHIKV infection
      in human patient. 

PMID- 24681088
TI  - Sex differences in Parkinson's disease and other movement disorders.
AB  - Movement disorders including Parkinson's disease (PD), Huntington's disease (HD),
      chorea, tics, and Tourette's syndrome (TS) display sex differences in disease
      susceptibility, disease pathogenesis, and clinical presentation. PD is more
      common in males than in females. Epidemiologic studies suggest that exposure to
      endogenous and exogenous estrogen contributes to these sex differences. There is
      extensive evidence that estrogen prevents dopaminergic neuron depletion induced
      by neurotoxins in PD animal models and therefore is neuroprotective. Estrogen may
      also decrease the efficacy of other neuroprotective substances such as caffeine
      in females but not males. Sex chromosomes can exert effects independent of sex
      steroid hormones on the development and maintenance of the dopamine system. As a
      result of hormone, chromosome and other unknown effects, there are sexual
      dimorphisms in the basal ganglia, and at the molecular levels in dopaminergic
      neurons that may lead to distinct mechanisms of pathogenesis in males and
      females. In this review, we summarize the evidence that estrogen and selective
      estrogen receptor modulators are neuroprotective in PD and discuss potential
      mechanisms of action. We also briefly review how sex differences in basal ganglia
      function and dopaminergic pathways may impact HD, chorea, and tics/Tourette's
      syndrome. Further understanding of these sex differences may lead to novel
      therapeutic strategies for prevention and treatment of these diseases. 

PMID- 24681090
TI  - Valence of physical stimuli, not housing conditions, affects behaviour and
      frontal cortical brain activity in sheep.
AB  - Modulation of short-term emotions by long-term mood is little understood but
      relevant to understand the affective system and of importance in respect to
      animal welfare: a negative mood might taint experiences, whilst a positive mood
      might alleviate single negative events. To induce different mood states in sheep
      housing conditions were varied. Fourteen ewes were group-housed in an
      unpredictable, stimulus-poor and 15 ewes in a predictable, stimulus-rich
      environment. Sheep were tested individually for mood in a behavioural cognitive
      bias paradigm. Also, their reactions to three physical stimuli thought to differ
      in their perceived valence were observed (negative: pricking, intermediate:
      slight pressure, positive: kneading). General behaviour, activity, ear movements
      and positions, and haemodynamic changes in the cortical brain were recorded
      during stimulations. Generalised mixed-effects models and model probabilities
      based on the BIC (Bayesian information criterion) were used. Only weak evidence
      for mood difference was found. Sheep from the unpredictable, stimulus-poor
      housing condition had a somewhat more negative cognitive bias, showed slightly
      more aversive behaviour, were slightly more active and moved their ears somewhat
      more. Sheep most clearly differentiated the negative from the intermediate and
      positive stimulus in that they exhibited more aversive behaviour, less nibbling,
      were more active, showed more ear movements, more forward ear postures, fewer
      backward ear postures, and a stronger decrease in deoxyhaemoglobin when subjected
      to the negative stimulus. In conclusion, sheep reacted towards stimuli according
      to their presumed valence but their mood was not strongly influenced by housing
      conditions. Therefore, behavioural reactions and cortical brain activity towards
      the stimuli were hardly modulated by housing conditions. 

PMID- 24681091
TI  - Natural products from resurrection plants: potential for medical applications.
AB  - Resurrection species are a group of land plants that can tolerate extreme
      desiccation of their vegetative tissues during harsh drought stress, and still
      quickly - often within hours - regain normal physiological and metabolic
      functions following rehydration. At the molecular level, this desiccation
      tolerance is attributed to basal cellular mechanisms including the constitutive
      expression of stress-associated genes and high levels of protective metabolites
      present already in the absence of stress, as well as to transcriptome and
      metabolome reconfigurations rapidly occurring during the initial phases of
      drought stress. Parts of this response are conferred by unique metabolites,
      including a diverse array of sugars, phenolic compounds, and polyols, some of
      which accumulate to high concentrations within the plant cell. In addition to
      drought stress, these metabolites are proposed to contribute to the protection
      against other abiotic stresses and to an increased oxidative stress tolerance.
      Recently, extracts of resurrection species and particular secondary metabolites
      therein were reported to display biological activities of importance to medicine,
      with e.g. antibacterial, anticancer, antifungal, and antiviral activities,
      rendering them possible candidates for the development of novel drug substances
      as well as for cosmetics. Herein, we provide an overview of the metabolite
      composition of resurrection species, summarize the latest reports related to the
      use of natural products from resurrection plants, and outline their potential for
      medical applications. 

PMID- 24681092
TI  - A rational approach to improving the biotechnological production of taxanes in
      plant cell cultures of Taxus spp.
AB  - Taxol is a complex diterpene alkaloid scarcely produced in nature and with a high
      anticancer activity. Biotechnological systems for taxol production based on cell
      cultures of Taxus spp. have been developed, but the growing commercial demand for
      taxol and its precursors requires the optimization of these procedures. In order
      to increase the biotechnological production of taxol and related taxanes in Taxus
      spp. cell cultures, it is necessary not only to take an empirical approach that
      strives to optimize in-put factors (cell line selection, culture conditions,
      elicitation, up-scaling, etc.) and out-put factors (growth, production, yields,
      etc.), but also to carry out molecular biological studies. The latter can provide
      valuable insight into how the enhancement of taxane biosynthesis and accumulation
      affects metabolic profiles and gene expression in Taxus spp. cell cultures.
      Several rational approaches have focused on studying the transcriptomic profiles
      of key genes in the taxol biosynthetic pathway in Taxus spp. cell cultures
      treated with elicitors such as methyl jasmonate, coronatine and cyclodextrins in
      relation with the taxane pattern, production and excretion to the culture medium.
      These studies have provided new insights into the taxol biosynthetic pathway and
      its regulation. Additionally, identifying genes with low levels of expression
      even in the presence of elicitors, together with metabolomics studies, has shed
      light on the limiting steps in taxol biosynthesis and could help define suitable
      metabolic targets for engineering with the main aim of obtaining highly
      productive Taxus cultured cells. In this review, we have summarized the latest
      endeavors to enhance the molecular understanding of the action mechanism of
      elicitors in Taxus spp. cell cultures. Developments in the ongoing search for new
      and more effective elicitation treatments and the application of metabolic
      engineering to design new transgenic cell lines of Taxus with an improved
      capacity for taxane production are described. 

PMID- 24681093
TI  - From nature to bedside: pro-survival and cell death mechanisms as therapeutic
      targets in cancer treatment.
AB  - Cell death is an important physiological regulator during development, tissue
      homeostasis and stress response but it is also a protective tumor suppressive
      mechanism. Tumor cells almost universally acquire the ability to evade cell death
      pathways that in normal cells act as a protective mechanism to remove damaged
      cells. As a result, a population of death-resistant cells with accumulating
      genetic and epigenetic abnormalities contributes to malignant transformation. Any
      alteration of the homeostatic balance between survival and death is therefore a
      critical factor in carcinogenesis. Several forms of cell death exist and cross
      talk among them is emerging; however, we still miss many molecular details. It
      becomes essential to revisit the role of each type of cell death to understand
      interconnections existing between different cell death pathways as well as the
      network of their mediators to eventually develop new effective strategies to kill
      cancer cells. More specifically, new therapies based on compounds selectively
      triggering apoptosis, necrosis or autophagy recently became both appealing and
      challenging. Despite the rather clear classification of the different cell death
      modalities according to morphological criteria and the attempt to describe them
      with distinct signaling pathways, the reality reveals a complex interplay between
      apoptosis, regulated necrosis and autophagy involving a heterogeneous mix of
      molecular mediators. Nature, presenting an almost endless plenitude of bioactive
      scaffolds, can efficiently contribute compounds that allow deciphering the
      intricate pathways of cell death pathways and thus eventually contribute to
      selectively target cancer-type specific pathways in an attempt to personalize
      cancer patient treatment depending on cancer death pathway specificities. The aim
      of this review is to provide first an overview of molecular cell death
      specificities and to highlight how compounds of natural origins, with or without
      hemisynthetic modifications, target unique thanatotic molecular constellations. 

PMID- 24681094
TI  - Colonic wall changes in patients with diverticular disease - is there a
      predisposition for a complicated course?
AB  - BACKGROUND: The aim of this study was to evaluate colonic wall changes and
      enteric neuropathy in patients with either uncomplicated (UDD) or complicated
      diverticular disease (CDD). Furthermore, we evaluated the presence of an anatomic
      sphincter at the rectosigmoid junction (RSJ). METHODS: Samples of colonic tissue
      from fifteen patients with UDD, fifteen patients with CDD and fifteen patients as
      control were collected. Collagen quotient I/III was measured with the Sirius-red
      test, expression of MMP-1, MMP-13, innervation (S100), proliferation (Ki67) and
      apoptosis (TUNEL) in the colonic wall were investigated by immunohistochemical
      studies. Furthermore, measurements of the different layers were performed to
      investigate the RSJ. RESULTS: Patients with either UDD or CDD had lower collagen
      I/III quotients compared to the control group, significant for CDD (p = 0.007).
      For MMP-1 and MMP-13 only a slight increase for patients with CDD was found. The
      percentage of proliferating (Ki67) and apoptotic (TUNEL) cells was significantly
      higher for patients with CDD than in the control group (p = 0.016; p = 0.037).
      Upon investigating the S100-expression a significant reduce in glial cells
      density was found in the myenteric and mucosal plexus for both groups (UDD and
      CDD) compared to the control group. Measurements of the different colon layers
      oral, aboral and at the RSJ revealed equal values. CONCLUSIONS: This study has
      shown that colonic wall changes and enteric neuropathy seem to play a role in the
      pathogenesis of colonic diverticulosis. None of our results suggest a
      predisposition for a complicated diverticular disease. Furthermore, the presence
      of an anatomic sphincter at the rectosigmoid junction could not be detected.

PMID- 24681095
TI  - Development and regulation of RORgammat(+) innate lymphoid cells.
AB  - RORgammat(+) innate lymphoid cells (ILCs), or ILC3, play a fundamental role in
      the development of lymphoid tissues, as well as in homeostasis and defence of
      mucosal tissues. These cells produce IL-22, IL-17A and LTalpha1beta2, key
      cytokines for the activation of epithelial defences and the recruitment of
      polymorphonuclear phagocytes. In the absence of ILC3, the early defence to
      infection and resistance to injury are compromised. Given the importance of ILC3
      in mucosal immunity, significant efforts are made to discover their multiple
      functions and decipher their mode of action and regulation. 

PMID- 24681096
TI  - Subunit CydX of Escherichia coli cytochrome bd ubiquinol oxidase is essential for
      assembly and stability of the di-heme active site.
AB  - Cytochrome bd ubiquinol oxidase uses the electron transport from ubiquinol to
      oxygen to establish a proton gradient across the membrane. The enzyme complex
      consists of subunits CydA and B and contains two b- and one d-type hemes as
      cofactors. Recently, it was proposed that a third subunit named CydX is essential
      for the function of the complex. Here, we show that CydX is indeed a subunit of
      purified Escherichia coli cytochrome bd oxidase and that the small protein is
      needed either for the assembly or the stability of the active site di-heme center
      and, thus, is essential for oxidase activity.

PMID- 24681097
TI  - AROS has a context-dependent effect on SIRT1.
AB  - The modulation of protein deacetylase SIRT1 has a vast therapeutic potential in
      treatment of several aging-associated diseases. Active regulator of SIRT1 (AROS)
      is a small endogenous protein which was originally reported to activate SIRT1
      through a direct interaction in cancer cells. We show that the interaction
      between the two proteins is weak and does not alter the activity of SIRT1 in non
      cancerous human cells. The results of different in vitro SIRT1 activity assays
      disclosed AROS as an inhibitor of SIRT1. The functional relationship between AROS
      and SIRT1 proved to be dependent on the biological context and experimental
      setting. 

PMID- 24681098
TI  - Dynamin related protein 1-dependent mitochondrial fission regulates oxidative
      signalling in T cells.
AB  - In T cells mitochondria-derived reactive oxygen species (ROS) are indispensible
      for activation of the transcription factor NF-kappaB, expression of cytokines and
      the CD95 ligand (CD95L/FasL). Here we show that activation-induced ROS generation
      is dependent on mitochondrial fission. Inhibition of dynamin related protein 1
      (Drp1) results in reduced ROS levels and transcriptional activity of NF-kappaB
      leading to diminished proliferation and CD95L-dependent activation-induced cell
      death (AICD). Upon stimulation Drp1 is S-nitrosylated, which is required for
      oxidative signalling, AICD and cytokine production. In conclusion, we describe a
      novel signalling pathway that links TCR-induced nitric oxide release to
      mitochondrial fission and oxidative signalling. 

PMID- 24681099
TI  - Functional intersection of Human Defensin 5 with the TNF receptor pathway.
AB  - Defensins are cationic antimicrobial peptides that contribute to regulation of
      host cell function also. Here, we report on the regulation of cell death by Human
      Defensin 5, the major antimicrobial peptide of ileal Paneth cells. We find that
      Human Defensin 5-mediated cellular effects depend on functional expression of
      Tumor Necrosis Factor receptors and downstream mediators of TNF signaling. Our
      data indicate the involvement of interactions between Human Defensin 5 and the
      extra-cellular domain of Tumor Necrosis Factor receptor 1. Human Defensin-5 also
      induces apoptosis intrinsically by targeting the mitochondrial membrane. 

PMID- 24681100
TI  - Beneficial modulation of the gut microbiota.
AB  - The human gut microbiota comprises approximately 100 trillion microbial cells and
      has a significant effect on many aspects of human physiology including
      metabolism, nutrient absorption and immune function. Disruption of this
      population has been implicated in many conditions and diseases, including
      examples such as obesity, inflammatory bowel disease and colorectal cancer that
      are highlighted in this review. A logical extension of these observations
      suggests that the manipulation of the gut microbiota can be employed to prevent
      or treat these conditions. Thus, here we highlight a variety of options,
      including the use of changes in diet (including the use of prebiotics),
      antimicrobial-based intervention, probiotics and faecal microbiota
      transplantation, and discuss their relative merits with respect to modulating the
      intestinal community in a beneficial way. 

PMID- 24681101
TI  - Antifreeze activity enhancement by site directed mutagenesis on an antifreeze
      protein from the beetle Rhagium mordax.
AB  - The ice binding motifs of insect antifreeze proteins (AFPs) mainly consist of
      repetitive TxT motifs aligned on a flat face of the protein. However, these
      motifs often contain non-threonines that disrupt the TxT pattern. We substituted
      two such disruptive amino acids located in the ice binding face of an AFP from
      Rhagium mordax with threonine. Furthermore, a mutant with an extra ice facing TxT
      motif was constructed. These mutants showed enhanced antifreeze activity compared
      to the wild type at low concentrations. However, extrapolating the data indicates
      that the wild type will become the most active at concentrations above 270 MUmol.

PMID- 24681103
TI  - Relationship between gut microbiota and development of T cell associated disease.
AB  - The interplay between the immune response and the gut microbiota is complex.
      Although it is well-established that the gut microbiota is essential for the
      proper development of the immune system, recent evidence indicates that the cells
      of the immune system also influence the composition of the gut microbiota. This
      interaction can have important consequences for the development of inflammatory
      diseases, including autoimmune diseases and allergy, and the specific mechanisms
      by which the gut commensals drive the development of different types of immune
      responses are beginning to be understood. Furthermore, sex hormones are now
      thought to play a novel role in this complex relationship, and collaborate with
      both the gut microbiota and immune system to influence the development of
      autoimmune disease. In this review, we will focus on recent studies that have
      transformed our understanding of the importance of the gut microbiota in
      inflammatory responses. 

PMID- 24681102
TI  - Tumor suppressor microRNAs: a novel non-coding alliance against cancer.
AB  - Tumor initiation and progression are the outcomes of a stepwise accumulation of
      genetic alterations. Among these, gene amplification and aberrant expression of
      oncogenic proteins, as well as deletion or inactivation of tumor suppressor
      genes, represent hallmark steps. Mounting evidence collected over the last few
      years has identified different populations of non-coding RNAs as major players in
      tumor suppression in almost all cancer types. Elucidating the diverse molecular
      mechanisms underlying the roles of non-coding RNAs in tumor progression might
      provide illuminating insights, potentially able to assist improved diagnosis,
      better staging and effective treatments of human cancers. Here we focus on
      several groups of tumor suppressor microRNAs, whose downregulation exerts a
      profound oncologic impact and might be harnessed for the benefit of cancer
      patients. 

PMID- 24681104
TI  - Association between intake of nutrients and food groups and liking for fat (The
      Nutrinet-Sante Study).
AB  - Apart from the established association between liking for fat and fat intake,
      little is known about the association between liking for fat and intake of
      specific nutrients or food groups. We investigated the association between
      dietary intake and liking for fat, fat-and-sweet and fat-and-salt. Liking scores
      were constructed using a validated preference questionnaire administered to
      41,595 French adults participating in the Nutrinet-Sante study. Dietary data were
      collected using web-based 24 h records. Relationships between liking and dietary
      intake were assessed using linear regression adjusted for age and energy intake.
      Results are expressed in percentage difference of intake between individuals with
      low liking and those with high liking. Compared with participants with low liking
      for fat, individuals with a strong liking for fat had higher intakes of total
      energy (+10.1% in women (W); +8.4% in men (M)), fats (W: +7.3%; M: +10.0%),
      saturated fats (W: +10.8%; M+15.4%), meat (W: +13.0%; M: +12.6%), butter (W:
      +34.0%; M: +48.1%), sweetened cream desserts (W: +14.8%; M: +21.1%) and croissant
      like pastries (W: +27.2%; M: +36.9). They also consumed lower quantities of omega
      3 fatty acids (W: -6.2%;M: -6.0%), fiber (W: -16.4%; M: -18.9%), fruits (W: 
      28.8%; M: -29.5%), vegetables (W: -16.4%; M: -19.7%) and yogurt (W: -12.1%; M: 
      14.8%). Participants with high liking for fat-and-salt had higher intakes of
      total energy, sodium and alcoholic beverages and lower consumption of total and
      simple carbohydrates and fruit and vegetables than persons with high liking for
      fat-and-sweet. Our study contributes to the understanding of liking as a
      determinant of dietary intake. It highlighted that increased liking for fat,
      especially fat-and-salt liking, was associated with a lower intake of healthy
      foods, such as fruit and vegetables.

PMID- 24681105
TI  - Family dinner frequency, settings and sources, and body weight in US adults.
AB  - Contemporary families and food systems are both becoming more dynamic and
      complex, and current associations between adult family meals and body mass index
      (BMI) are not well understood. This investigation took a new approach by
      examining diverse settings and sources of food for family dinners in relationship
      to BMI in a cross-sectional nationally representative survey of 360 US adults age
      18-85 living with family members. In this sample, 89% of adults ate family
      dinners at least 5 days per week and almost all ate family dinners cooked and
      eaten at home. About half of these adults also ate family dinners at restaurants,
      fast food places, or ate takeout food at home, and less common were family
      dinners at homes of relatives or friends. Family dinners eaten at fast food
      places, but not other settings or sources, were significantly associated with
      higher BMI. Overall, adult family dinners were commonplace, usually involved home
      cooking, and when at fast food places may be related with higher adult body
      weights. 

PMID- 24681106
TI  - Opportunities for healthier child feeding. Does ethnic position matter? - self
      reported evaluation of family diet and impediments to change among parents with
      majority and minority status in Denmark.
AB  - Health inequality between ethnic groups is expressed in differences in the
      prevalence of diet related diseases. The aim of the study was to investigate and
      compare barriers toward eating healthier among ethnic majority and minority
      parents in Denmark. A postal survey was carried out among 2511 parents with
      either Danish or non-western ethnic minority descendant background, investigating
      barriers on cultural, structural, social, individual, and practical levels. The
      results showed that compared with parents of Danish origin, ethnic minority
      parents were more likely to evaluate their own diets negatively (OR 3.0, CI 1.7
      5.3), and to evaluate their children's diets negatively (OR 4.6, CI 2.5-8.4). In
      addition, ethnic minority parents to a higher degree experienced barriers to
      eating healthier than Danish parents did. Most salient was ethnic minority
      parents' expression of a lack of control over their own food intake and the food
      given to their children in everyday life. Such a lack of control was identified
      on practical, social, structural and individual levels. Young age of the parents
      was found to explain some of the differences between ethnic groups. It is
      concluded that dietary interventions directed at parents of small children should
      address not only cultural background but also barriers operating on practical,
      social, structural, and individual levels, as some of these influence ethnic
      minorities and the majority population differently. Further exploration of the
      importance of young age and the interplay between structural and cultural factors
      in the lives of ethnic minority families is needed. 

PMID- 24681107
TI  - Immunomodulation of mesenchymal stromal cells on regulatory T cells and its
      possible mechanism.
AB  - Mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs) have both
      garnered abundant interests from immunologists worldwide, as both MSCs and Tregs
      can be considered immunosuppressive in their own right. But a little attention
      has been paid to the impacts of MSCs on Tregs. To clarify the effects of MSCs on
      Tregs, we performed the coculture systems within MSCs and Tregs. We confirmed
      that MSC-exposed Tregs are capable of more immunosuppressive than Tregs without
      coculturing with MSCs. And this augmenting suppressive capacity was accompanied
      with an upregulation of programmed cell death 1 receptor (PD-1) on Tregs.
      Importantly, we found that cell viability of Tregs was excluded from the
      influences of MSCs. Finally, we showed that PD-1/B7-H1 interactions and IL-10
      might be responsible for the enhanced suppressive capability of MSC-exposed
      Tregs. Further analysis revealed that PD-1/B7-H1 interactions were not
      responsible for the productions of IL-10 and TGF-beta1 in the MSC-Treg coculture
      systems; in contrast, IL-10 rather than TGF-beta1 played a role in the
      upregualtion of PD-1. Furthermore, this is the first explorative study to
      evaluate the immunomodulation of MSCs on the suppressive capacity of Tregs in MSC
      Treg in vitro coculture setting. 

PMID- 24681108
TI  - How are patient populations characterized in studies investigating depression in
      advanced cancer? Results from a systematic literature review.
AB  - CONTEXT: Prevalence rates of depression in patients with advanced cancer vary
      considerably. This may be because of heterogeneous samples and use of different
      assessment methods. Adequate sample descriptions and consistent use of measures
      are needed to be able to generalize research findings and apply them to clinical
      practice. OBJECTIVES: Our objective was twofold: First, to investigate which
      clinically important variables were used to describe the samples in studies of
      depression in patients with advanced cancer; and second, to examine the methods
      used for assessing and classifying depression in these studies. METHODS: PubMed,
      PsycINFO, Embase, and CINAHL were searched combining search term groups
      representing "depression," "palliative care," and "advanced cancer" covering 2007
      2011. Titles and abstracts were screened, and relevant full-text articles were
      evaluated independently by two authors. Information on 32 predefined variables on
      cancer disease, treatment, sociodemographics, depression-related factors, and
      assessment methods was extracted from the articles. RESULTS: After removing
      duplicates, 916 citations were screened of which 59 articles were retained. Age,
      gender, and stage of the cancer disease were the most frequently reported
      variables. Depression-related variables were rarely reported, for example,
      antidepressant use (17%) and previous depressive episodes (12%). Only 25% of the
      studies assessed and classified depression according to a validated diagnostic
      system. CONCLUSION: Current practice for describing sample characteristics and
      assessing depression varies greatly between studies. A more standardized practice
      is recommended to enhance the generalizability and utility of findings.
      Stakeholders are encouraged to work toward a common standard for sample
      descriptions.

PMID- 24681109
TI  - Ethical considerations in the management of analgesia in terminally ill pediatric
      patients.
AB  - Research has demonstrated the significant symptom burden present at the end of
      life of terminally ill children. Medicine has always viewed the relief of pain
      and suffering as a fundamental human right and a moral and ethical obligation. At
      the end of life, pain and dyspnea are symptoms commonly experienced by both
      adults and children. Opioids are the mainstay in treating the suffering
      associated with pain and dyspnea; however, there exist several barriers to the
      use of opioids. We describe a case in which parents prevent a young patient from
      receiving adequate pain management during the course of a terminal illness. We
      discuss the importance of recognizing the barriers to opioid use and the ethical
      ramifications of failing to find common ground with the family. We highlight
      parental responsibilities and limitations of parental authority in decision
      making for their child. 

PMID- 24681110
TI  - Documentation quality of inpatient code status discussions.
AB  - CONTEXT: Accurate documentation of inpatient code status discussions (CSDs) is
      important because of frequent patient care handoffs. OBJECTIVES: To examine the
      quality of inpatient CSD documentation and compare documentation quality across
      physician services. METHODS: This was a retrospective study of patients
      hospitalized between January 1 and June 30, 2011 with a new or canceled do-not
      resuscitate (DNR) order at least 24 hours after hospital admission. We developed
      a chart abstraction tool to assess the documentation of five quality elements: 1)
      who the DNR discussion was held with, 2) patient goals/values, 3) prognosis, 4)
      treatment options and resuscitation outcomes, and 5) health care power of
      attorney (HCPOA). RESULTS: We identified 379 patients, of whom 235 (62%) had a
      note documenting a CSD. After excluding patients lacking a note from their
      primary service, 227 remained for analysis. Sixty-three percent of notes
      contained documentation of who the discussion was held with. Patient goals/values
      were documented in 43%, discussion of prognosis in 14%, treatment options and
      resuscitation outcomes in 40%, and HCPOA in 29%. Hospitalists were more likely
      than residents to document who the discussion was held with (P < 0.001) and
      patient goals/values (P < 0.001), whereas internal medicine residents were more
      likely to document HCPOA (P = 0.04). The mean number of elements documented for
      hospitalists was 2.40, followed by internal medicine residents at 2.07, and non
      internal medicine trainees at 1.30 (P < 0.001). CONCLUSION: Documentation quality
      of inpatient CSDs was poor. Our findings highlight the need to improve the
      quality of resident and attending CSD documentation.

PMID- 24681111
TI  - Psychometric properties of the Polish version of the Multidimensional Fatigue
      Inventory-20 in cancer patients.
AB  - CONTEXT: Multidimensional questionnaires estimating cancer-related fatigue (CRF)
      as a symptom cluster or a clinical syndrome primarily have been used and
      validated in English-speaking populations. However, cultural issues and language
      peculiarities can affect CRF assessment OBJECTIVES: The main aims of this study
      were to evaluate the psychometric properties of the Polish version of the
      Multidimensional Fatigue Inventory-20 (MFI-20) and to deliver to clinicians a
      multidimensional tool for CRF assessment in Polish-speaking patients with cancer.
      METHODS: After forward-backward translation procedures, the Polish version of MFI
      20 was administered to 340 cancer patients. The Polish MFI-20 was appraised in
      terms of acceptability, reliability, and validity. Internal consistency was
      assessed by calculating Cronbach's alpha coefficients. Structural validity was
      evaluated with confirmatory factor analysis. RESULTS: The translated MFI-20 was
      well accepted; 90% of subjects fully completed the questionnaire. The overall
      Cronbach's alpha coefficient was 0.9, ranging from 0.57 to 0.81. All correlation
      coefficients among Numeric Rating Scale-fatigue, fatigue-related items from the
      European Organization for Research and Treatment of Cancer Quality of Life Core
      30 questionnaire, and the MFI--20 were statistically significant (P < 0.001).
      Confirmatory factor analysis demonstrated good structural validity and revealed
      only three dimensions in the Polish version of the MFI-20-physical and mental
      fatigue as well as reduced motivation. CONCLUSION: The Polish version of the MFI
      20 is well accepted by patients, reliable, and a valid instrument to assess CRF
      in Polish cancer patients.

PMID- 24681112
TI  - The protein-vesicle network of autophagy.
AB  - The biogenesis of autophagosomes entails the nucleation and growth of a double
      membrane sheet, the phagophore, which engulfs cytosol for delivery to the
      lysosome. Genetic studies have identified a class of Atg proteins that are
      essential for the process, yet the molecular mechanism of autophagosome
      biogenesis has been elusive. Proteomic, structural, super-resolution imaging, and
      biochemical reconstitution experiments have begun to fill in some of the gaps.
      This review describes progress and prospects for obtaining a four-dimensional
      network model of the nucleation and growth of the phagophore. 

PMID- 24681113
TI  - RNA interference-mediated knockdown of Notch-1 inhibits migration and invasion,
      down-regulates matrix metalloproteinases and suppresses NF-kappaB signaling
      pathway in trophoblast cells.
AB  - Preeclampsia is well known to present with reduced trophoblast invasion into the
      placental bed. Notch-1, a ligand-activated transmembrane receptor, has been
      reported to be down-regulated in preeclamptic human placentas. This study was
      conducted to explore the role of Notch-1 in the cell migration and invasion of a
      human trophoblast cell line, JEG3 cells. Short hairpin RNA (shRNA)-mediated RNA
      interference was performed to effectively suppress the endogenous expression of
      Notch-1 at both mRNA and protein levels in JEG3 cells. Results of wound healing
      and transwell assays showed that knockdown of Notch-1 reduced trophoblast cell
      migration and invasion. The protein expressions and activities of matrix
      metalloproteinase (MMP)-2 and MMP-9 were reduced in JEG3 cell when Notch-1 was
      decreased. Furthermore, the epithelial-cadherin (E-cadherin) expression increased
      in JEG3 cells when Notch-1 was inhibited, whereas its suppressor Snail decreased
      in these cells. Moreover, knockdown of Notch-1 also suppressed NF-kappaB
      signaling pathway by inhibiting the phosphorylation of nuclear factor kappa B (NF
      kappaB p65) inhibitor (IkappaBalpha) and the subsequent nuclear translocation of
      NF-kappaB subunit p65 in JEG3 cells. In summary, we demonstrate that Notch-1
      contributes to trophoblast cell migration and invasion and that it may be
      involved in the pathology of human preeclampsia.

PMID- 24681114
TI  - The inconvenient truth of elevated left atrial pressure and AF recurrence despite
      catheter ablation.

PMID- 24681115
TI  - Atrial fibrillation ablation using open-irrigated tip radiofrequency: experience
      with intraprocedural activated clotting times <=210 seconds.
AB  - BACKGROUND: Atrial fibrillation (AF) ablation procedures generally use
      intraprocedural activated clotting time (ACT) of >300-350 seconds to prevent
      thromboembolic events. OBJECTIVE: To evaluate bleeding and thromboembolic
      procedural complications in patients with symptomatic AF undergoing ablation
      procedures with low intraprocedural ACT. METHODS: We examined a subset of 372 of
      2334 (15.9%) AF ablation procedures using open-irrigated tip radiofrequency
      catheters at 50 W, interrupted oral anticoagulation, and a target ACT of 225
      seconds, with average ACT <=210 seconds. RESULTS: There were 372 ablation
      procedures in 339 patients with average ACT <=210 seconds. Patient demographic
      characteristics were as follows: age 60.9 +/- 9.4 years, men 269 (79.3%), left
      atrial (LA) size 4.27 +/- 0.65 cm, prior stroke/transient ischemic attack 24
      (7.1%), CHADS2 score 0.94 +/- 0.98, and CHA2DS2-VASc score 1.53 +/- 1.35. AF type
      was categorized as paroxysmal in 107 (31.6%), persistent in 200 (59.0%), and long
      standing persistent in 32 (9.4%). Procedural and LA times were 119 +/- 26 and 82
      +/- 24 minutes. Patients underwent preprocedure transesophageal echocardiography.
      The heparin bolus (8738 +/- 2823 units, 93.4 mg/kg) was given after LA access,
      and the maintenance infusion was 1000 units/hour via a single transseptal sheath
      with subsequent adjustments based on ACT values. The average ACT was 202 +/- 7.5
      seconds per procedure, with 116 patients with average ACT <200 seconds and 16
      patients with all ACTs <200 seconds. Complications occurred in 7 of 372 (1.9%)
      ablation procedures, including 2 pericardial tamponades (0.54%), 1 groin
      pseudoaneurysm (0.27%), and 1 pulmonary embolus, several weeks postablation.
      There were no other bleeding events and no strokes/transient ischemic attacks or
      systemic thromboemboli. CONCLUSION: Using open-irrigated tip radiofrequency
      catheters at 50 W and preablation transesophageal echocardiography as well as
      infusing maintenance heparin through a single transseptal sheath, AF ablation can
      be performed safely despite ACT averaging <=210 seconds. While we are not
      advocating target ACTs this low, our data suggest that long ACTs may not be
      absolutely necessary for preventing thromboembolic events. Lower target ACTs may
      potentially reduce bleeding complications.

PMID- 24681116
TI  - Resetting and entrainment of reentrant ventricular tachycardia associated with
      myocardial infarction.
AB  - Resetting and entrainment are specific responses to programmed stimulation that
      are useful in determining the mechanism of ventricular tachycardia (VT),
      localizing critical components of a reentrant circuit to guide ablation,
      determining how antiarrhythmic drugs affect the tachycardia, and developing
      antitachycardia pacing modalities. While resetting and entrainment have certain
      things in common, they differ significantly in the ability to characterize the
      properties of VT. Only resetting, which is the interaction of a single
      extrastimulus with the tachycardia, can characterize the properties of the VT
      itself. Entrainment assesses the effect of overdrive pacing on a reset circuit,
      not the VT itself. The terms for these techniques are often incorrectly used
      interchangeably. The present review details the characteristics and uses of both
      stimulation techniques. 

PMID- 24681117
TI  - Rivaroxaban postmarketing risk of liver injury.
AB  - BACKGROUND & AIMS: Rivaroxaban is an oral direct factor Xa inhibitor that has
      been marketed worldwide since 2008 for the primary and secondary prevention and
      treatment of thromboembolic disorders. Although liver injury was observed in
      premarketing trials of rivaroxaban, there are no published postmarketing cases of
      liver injury associated with rivaroxaban. METHODS: Report of 14 cases of liver
      injury associated with rivaroxaban, including two with liver biopsy, and search
      queries in three large international pharmacovigilance databases for comparable
      cases. RESULTS: Formal causality assessment classified rivaroxaban as the "highly
      probable", "probable", and "possible" cause in 4, 7, and 3 patients,
      respectively. Search results from three large international pharmacovigilance
      databases revealed a considerable number of additional hepatic adverse events
      where rivaroxaban was reported as a suspected cause. CONCLUSIONS: We interpret
      the presented information as a relevant safety signal that should be followed by
      pharmacoepidemiological studies in order to reliably estimate absolute and
      relative risks of liver injury associated with rivaroxaban in support of rational
      risk-benefit assessment. Meanwhile, incident symptoms and signs of liver disease
      in patients treated with rivaroxaban should be considered as a potential adverse
      drug reaction, and if no other likely cause can be identified rivaroxaban should
      be stopped as soon as possible.

PMID- 24681118
TI  - Metallothionein mRNA induction is correlated with the decrease of DNA strand
      breaks in cadmium exposed zebra mussels.
AB  - We have previously shown that cadmium (Cd) and benzo[a]pyrene (BaP) induced early
      DNA damages in zebra mussels, and that the level of DNA strand breaks (SB)
      returned to a basal level after 3 days of exposure to Cd. The aim of the present
      study was to go further in the mechanisms of Cd and BaP detoxification. For that
      purpose, expression of genes encoding for metallothionein (MT), aryl hydrocarbon
      receptor (AHR), P-gp, catalase, glutathione S-transferase and heat shock protein
      70 (HSP70) proteins have been measured using RT-qPCR. Data reported here show
      that Cd is a strong inducer of MT and HSP70 genes, and that BaP is a strong
      inducer of P-gp and AHR genes. Exposure to Cd and BaP resulted in moderate
      changes in antioxidant enzymes mRNA. Since the increase of MT mRNA occurred when
      the DNA SB level returned to its basal level, we can suggest that MT is
      implicated in cadmium detoxification. 

PMID- 24681119
TI  - Spontaneous genetic damage in the tegu lizard (Tupinambis merianae): the effect
      of age.
AB  - Several studies indicate that certain factors such as age, sex or nutritional
      status among others, may affect the level of DNA damage, both induced and
      spontaneous, so it is very important to consider them for a more accurate
      interpretation of the findings. The aim of this study was to analyze the
      influence of age, sex, and nest of origin on spontaneous genetic damage of
      Tupinambis merianae determined by the comet assay (CA) and the micronucleus (MN)
      test, in order to improve reference data for future in vivo studies of
      xenobiotics exposure in this species. Sixty-five tegu lizards of three different
      ages: newborns (NB), juveniles (JUV) and adults (AD), both sexes and from
      different nests of origin were used. Blood samples were collected from the caudal
      vein of all animals and the MN test and CA were applied on peripheral blood
      erythrocytes to determine basal frequency of MN (BFMN) and basal damage index
      (BDI). The comparison between age groups showed statistically significant
      differences in the BFMN and BDI (p<0.05). NB animals showed significantly higher
      BDI values in relation to JUV and AD (p<0.016), but no statistically differences
      were found between the latter two. NB showed lower BFMN respect to other age
      groups, being statistically significant only when compared to AD (p<0.016). BFMN
      or BDI showed no statistically significant differences between sexes or nests of
      origin (p>0.05). A weak negative relationship was found only between BFMN and
      weight of NB tegu lizard (p=0.014; R(2)=0.245). Basal values of genetic damage
      obtained with both biomarkers in the tegu lizard evidenced that age is an
      intrinsic factor that should be taken into account to avoid misunderstanding of
      the results in future biomonitoring studies. 

PMID- 24681120
TI  - Determination of the (137)Cs and (90)Sr radioisotope activity concentrations
      found in digestive organs of sheep fed with different feeds.
AB  - In this study, 12 weanling lambs were fed for 6 months at the Vetenary Control
      and Research Institute of Elazig in Turkey. Sheep were divided into two groups
      according to feeding type. Each group of sheep was fed a different amount of
      feed. The activity concentrations of (137)Cs and (90)Sr were determined in rumen,
      small intestine and large intestine tissue samples of sheep fed various feeds and
      quantities. Transfer coefficients and concentration ratios were estimated. The
      highest average (137)Cs and (90)Sr activity concentrations were 82 +/- 22 Bq kg(
      1) fw in the straw group small intestine sample and 74 +/- 9.0 Bq kg(-1) fw in
      the fresh lucerne group rumen sample, respectively. Radioactivity levels for
      (137)Cs and (90)Sr are under the maximum permitted radioactive pollution level
      for all the samples. The transfer coefficient of (137)Cs and (90)Sr in the
      samples of sheep ranged from 1.0 * 10(-1) to 2.1 * 10(0) d kg(-1) and 1.7 * 10(
      1) to 2.3 * 10(0) d kg(-1), respectively. Calculated transfer coefficients of
      (90)Sr and (137)Cs in the samples of sheep were higher than the expected values.
      Geometric means of Ff and CR for (137)Cs were maximum in the fresh lucerne group
      large intestine sample. Geometric means of Ff and CR for (90)Sr were maximum in
      the fresh lucerne group small intestine sample. 

PMID- 24681121
TI  - Molecular characterization and tissue expression of peptide YY in Schizothorax
      prenanti: effects of periprandial changes and fasting on expression in the
      hypothalamus.
AB  - Peptide YY (PYY) is a potent anorectic neuropeptide implicated in feeding
      regulation in mammals. However, the involvement of PYY in the feeding behavior of
      teleosts has not been well understood. In this study, we employed molecular, real
      time quantitative PCR and physiological studies to characterize the structure,
      distribution, and appetite regulatory effects of PYY in Schizothorax prenanti (S.
      prenanti). A very high conservation in PYY sequences was found in teleosts. PYY
      is widely expressed, with the highest levels of expression in telencephalon,
      medulla oblongata, pituitary and hypothalamus of S. prenanti. The PYY mRNA
      expression in the hypothalamus was highly elevated after a meal, suggesting a
      satiety signal role for PYY in S. prenanti. In addition, PYY gene expression in
      the hypothalamus was decreased after fasting and increased sharply after
      refeeding, which suggested that PYY might be involved in the central regulation
      of appetite in S. prenanti. Overall, our result provides basis for further
      investigation into the regulation of feeding in S. prenanti. 

PMID- 24681122
TI  - Structure-based predictors of resistance to the HIV-1 integrase inhibitor
      Elvitegravir.
AB  - The enzyme integrase (IN) of human immunodeficiency virus type 1 (HIV-1) mediates
      integration of reverse transcribed viral DNA into the human genome, an essential
      step in the HIV-1 replication cycle. Elvitegravir (EVG) is an HIV-1 strand
      transfer inhibitor that binds IN and is the second drug in its class to be
      approved for clinical use in combination with other anti-HIV-1 medications.
      However, certain IN sequence mutational patterns have an effect on inhibitor
      binding, thereby altering the degree of IN mutant susceptibility to EVG.
      Employing a dataset of 115 translated IN sequences, each having a known EVG
      susceptibility value and consisting of a distinct set of amino acid replacements
      relative to the native IN, here we develop and evaluate statistical learning
      models for predicting the phenotypes (i.e., quantified EVG susceptibilities) of
      new IN mutants based solely on their genotypes (i.e., translated IN sequences).
      Each IN mutant is represented as a feature vector of structure-based attributes
      obtained via an in silico mutagenesis procedure that quantifies all anticipated
      IN residue-specific environmental perturbations from wild type upon mutation.
      Cross-validated performance based on four classification models show that
      balanced accuracy reaches 87%, while two regression models yield a Pearson's
      correlation coefficient as high as r=0.78. At the present time, the models may
      potentially be useful for diagnostic purposes, but only in conjunction with other
      tools and techniques, including experimental phenotype assays. However, as
      published experimental phenotypes for new IN variants become available, a larger
      and more diverse training set will likely lead to significantly more accurate
      models. 

PMID- 24681123
TI  - Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine
      epidemic diarrhea virus propagation.
AB  - The unfolded protein response (UPR) is cyto-protective machinery elicited towards
      an influx of large amount of protein synthesis in the endoplasmic reticulum (ER).
      Extensive studies suggest that the UPR can also be activated during virus
      infection. In the present studies, we first evaluated if porcine epidemic
      diarrhea virus (PEDV) infection activated the UPR pathways. Electron microscopy
      analysis demonstrated the morphology changes of ER post-PEDV infection. Western
      blot and real-time PCR identified the differences of UPR genes in response to
      PEDV infection. The results suggested that PEDV infection induced UPR in Vero
      cells. Meanwhile, we silenced the expression of PKR-like ER kinase (PERK) by
      shRNA, we found that the knockdown of PERK increased virus loads in the cells,
      which was consistent with the result on 4-phenylbutyrate (4-PBA) treatment. We
      next determined whether 2-Deoxy-d-glucose (2-DG), an ER stress inducer, possessed
      antiviral activity against PEDV infection. Plaque formation assay, RT-PCR and
      Western blot analysis suggested that 2-DG might inhibit virus infection by
      affecting viral protein translation during the early stage of virus infection.
      Interestingly, we also found that 2-DG treatment could affect virus assembly,
      which is similar to previous studies on influenza virus. All these results
      support the therapeutic potential of using 2-DG or glucose/mannose analogs to
      induce the UPR to block virus replication. 

PMID- 24681124
TI  - A novel neutralizing antibody against diverse clades of H5N1 influenza virus and
      its mutants capable of airborne transmission.
AB  - Highly pathogenic avian influenza A virus H5N1 continues to spread among poultry
      and has frequently broken the species barrier to humans. Recent studies have
      shown that a laboratory-mutated or reassortant H5N1 virus bearing hemagglutinin
      (HA) with as few as four or five mutations was capable of transmitting more
      efficiently via respiratory droplets between ferrets, posing a serious threat to
      public health and underscoring the priority of effective vaccines and
      therapeutics. In this study, we identified a novel monoclonal antibody (mAb)
      named HAb21, that has a broadly neutralizing activity against all tested strains
      of H5N1 covering clades 0, 1, 2.2, 2.3.4, and 2.3.2.1. Importantly, HAb21
      efficiently neutralized diverse H5N1 variants with single or combination forms of
      mutations capable of airborne transmission. We demonstrated that HAb21 blocked
      viral entry during the receptor-binding step by targeting a previously
      uncharacterized epitope at the tip of the HA head. This novel epitope closely
      neighbors the receptor-binding site (RBS) and the interface of HA trimer and is
      highly conserved among divergent H5N1 strains. Our studies provide a new tool for
      use either for therapeutic purposes or as a basis of vaccine development. 

PMID- 24681125
TI  - One Health approach to Rift Valley fever vaccine development.
AB  - Since its discovery in the 1930s, Rift Valley fever virus (RVFV) spread across
      the African continent and invaded the Arabian Peninsula and several islands off
      the coast of Southeast Africa. The virus causes recurrent outbreaks in these
      regions, and its continued spread is of global concern. Next-generation
      veterinary vaccines of improved efficacy and safety are being developed that can
      soon be used for the widespread vaccination of livestock. However, due to
      regulatory and economic challenges, vaccine manufacturers have been reluctant to
      develop a human vaccine. Recent innovations in veterinary vaccinology, animal
      models and licensing strategies can now be used to overcome these hurdles. This
      paper reviews the historical impact of RVFV on human health and proposes
      strategies to develop and license a next-generation vaccine for both animals and
      humans. 

PMID- 24681126
TI  - Giant nonfamilial left atrial myxoma presenting with eye embolism and nonvalvular
      Streptococcus sanguinis endocarditis.

PMID- 24681127
TI  - Effects of ethanol and acetaldehyde in zebrafish brain structures: an in vitro
      approach on glutamate uptake and on toxicity-related parameters.
AB  - Ethanol (EtOH) and its metabolite, acetaldehyde (ALD), induce deleterious effects
      on central nervous system (CNS). Here we investigate the in vitro toxicity of
      EtOH and ALD (concentrations of 0.25%, 0.5%, and 1%) in zebrafish brain
      structures [telencephalon (TE), opticum tectum (OT), and cerebellum (CE)] by
      measuring the functionality of glutamate transporters, MTT reduction, and
      extracellular LDH activity. Both molecules decreased the activity of the Na(+)
      dependent glutamate transporters in all brain structures. The strongest glutamate
      uptake inhibition after EtOH exposure was 58% (TE-1%), and after ALD, 91% (CE
      1%). The results of MTT assay and LDH released demonstrated that the actions of
      EtOH and its metabolite are concentration and structure-dependent, in which ALD
      was more toxic than EtOH. In summary, our findings demonstrate a differential
      toxicity in vitro of EtOH and ALD in zebrafish brain structures, which can
      involve changes on glutamatergic parameters. We suggest that this species may be
      an interesting model for assessing the toxicological actions of alcohol and its
      metabolite in CNS. 

PMID- 24681128
TI  - Idiosyncratic drug-induced liver injury is associated with substantial morbidity
      and mortality within 6 months from onset.
AB  - BACKGROUND & AIMS: Little is known about the incidence of drug-induced liver
      injury (DILI) and risk factors for adverse outcomes. We evaluated short-term
      outcomes of a large cohort of patients with DILI enrolled in an ongoing
      multicenter prospective study. METHODS: Data were collected from 660 adults with
      definite, highly likely, or probable DILI. Regression methods were used to
      identify risk factors for early liver-related death or liver transplantation and
      chronic liver injury. RESULTS: Patients' median age was 51.4 years; 59.5% were
      female and 59.1% required hospitalization. Within 6 months of DILI onset, 30
      patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%
      6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related.
      Asian race, absence of itching, lung disease, low serum albumin levels, low
      platelet counts, and high serum levels of alanine aminotransferase and total
      bilirubin at presentation were independent risk factors for reduced times to
      liver-related death or liver transplantation (C-statistic = 0.87). At 6 months
      after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver
      damage. African-American race, higher serum levels of alkaline phosphatase, and
      prior heart disease or malignancy requiring treatment were independent risk
      factors for chronic DILI (C-statistic = 0.71). CONCLUSIONS: Nearly 1 in 10
      patients die or undergo liver transplantation within 6 months of DILI onset and
      nearly 1 in 5 of the remaining patients have evidence of persistent liver injury
      at 6 months. The profile of liver injury at presentation, initial severity,
      patient's race, and medical comorbidities are important determinants of the
      likelihood of death/transplantation or persistent liver injury within 6 months.

PMID- 24681129
TI  - Tissue engineering in the gut: developments in neuromusculature.
AB  - The complexity of the gastrointestinal (GI) tract lies in its anatomy as well as
      in its physiology. Several different cell types populate the GI tract, adding to
      the complexity of cell sourcing for regenerative medicine. Each cell layer has a
      specialized function in mediating digestion, absorption, secretion, motility, and
      excretion. Tissue engineering and regenerative medicine aim to regenerate the
      specific layers mimicking architecture and recapitulating function.
      Gastrointestinal motility is the underlying program that mediates the diverse
      functions of the intestines, as an organ. Hence, the first logical step in GI
      regenerative medicine is the reconstruction of the tubular smooth musculature
      along with the drivers of their input, the enteric nervous system. Recent
      advances in the field of GI tissue engineering have focused on the use of
      scaffolding biomaterials in combination with cells and bioactive factors. The
      ability to innervate the bioengineered muscle is a critical step to ensure proper
      functionality. Finally, in vivo studies are essential to evaluate implant
      integration with host tissue, survival, and functionality. In this review, we
      focus on the tubular structure of the GI tract, tools for innervation, and,
      finally, evaluation of in vivo strategies for GI replacements. 

PMID- 24681130
TI  - Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma.

PMID- 24681131
TI  - Analysis of the heterochromatin protein 1 (HP1) interactome in Drosophila.
AB  - Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as
      a heterochromatin associated protein required for epigenetic gene silencing. Most
      eukaryotes have at least three HP1 homologs that play differential roles in
      heterochromatin and euchromatin. However, despite the fact that the three HP1
      proteins bind to different regions of the genome, several studies show that most
      of the interactions occur in a manner specific to HP1a. In addition, little is
      known about the overall interaction network of the three Drosophila HP1 homologs,
      HP1a, HP1b, and HP1c. Here, we performed the first comprehensive proteomic
      analysis of Drosophila HP1 homologs by coupling a double-affinity purification
      approach with MudPIT analysis to identify interacting proteins of Drosophila HP1.
      We discovered 160-310 proteins co-eluted with HP1, including a number of novel
      HP1-binding partners along with the previously identified HP1 binding proteins.
      Finally, we showed that slight and unique binding preferences might exist between
      the three HP1 proteins in Drosophila. These studies are the first to
      systematically analyze the interactome of HP1 paralogs and provide the basic
      clues as to the molecular mechanism by which HP1 might control cellular
      processes. BIOLOGICAL SIGNIFICANCE: Most eukaryotes have at least three HP1
      homologs with similar domain structures but with differential roles in
      heterochromatin and euchromatin. However, little is known about the overall
      interactome of the three Drosophila HP1 homologs, HP1a, HP1b, and HP1c. The
      present study compared interacting proteins of three HP1 homologs in Drosophila.
      To better understand the underlying mechanisms for gene regulation of HP1, a
      double-affinity purification and MudPIT mass spectrometry were employed to
      identify differential proteins as well as common binding proteins of HP1.
      Therefore, this study provides not only the comparative proteomic analysis but
      also molecular mechanism underlying the HP1 homolog-specific function.

PMID- 24681132
TI  - The proteomics quantification dilemma.
AB  - Proteomics is dominated today by the protein expression discourse, which
      favorites the bottom-up approach because of its high throughput and its high
      sensitivity. For quantification this proceeding is misleading, if a protein is
      present with more than one protein species in the sample to be analyzed. The
      protein speciation discourse considers this more realistic situation and affords
      the top-down procedures or at least a separation of the protein species in
      advance to identification and quantification. Today all of the top-down
      procedures are one order of magnitude less sensitive than the bottom-up ones. To
      increase sensitivity and to increase throughput are major challenges for
      proteomics of the next years. This article is part of a Special Issue entitled:
      20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini,
      Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. 

PMID- 24681133
TI  - Bleeding after PCI, vascular access, and falsification endpoints in observational
      studies.

PMID- 24681134
TI  - Dark chocolate intake buffers stress reactivity in humans.

PMID- 24681135
TI  - Reply: Bleeding after PCI, vascular access, and falsification endpoints in
      observational studies.

PMID- 24681136
TI  - Revascularization strategies in patients with combined carotid and coronary
      artery disease.

PMID- 24681137
TI  - The missing link between high-density lipoprotein cholesterol and inflammatory
      response in cardiovascular disease.

PMID- 24681138
TI  - Going mobile: enhanced recovery from myocardial infarction via stem cell
      mobilization and homing for tissue repair.

PMID- 24681139
TI  - NOX2-induced myocardial fibrosis and diastolic dysfunction: role of the
      endothelium.

PMID- 24681140
TI  - Significant mitral regurgitation left untreated at the time of aortic valve
      replacement: a comprehensive review of a frequent entity in the transcatheter
      aortic valve replacement era.
AB  - Significant mitral regurgitation (MR) is frequent in patients with severe aortic
      stenosis (AS). In these cases, concomitant mitral valve repair or replacement is
      usually performed at the time of surgical aortic valve replacement (SAVR).
      Transcatheter aortic valve replacement (TAVR) has recently been considered as an
      alternative for patients at high or prohibitive surgical risk. However,
      concomitant significant MR in this setting is typically left untreated. Moderate
      to severe MR after aortic valve replacement is therefore a relevant entity in the
      TAVR era. The purpose of this review is to present the current knowledge on the
      clinical impact and post-procedural evolution of concomitant significant MR in
      patients with severe AS who have undergone aortic valve replacement (SAVR and
      TAVR). This information could contribute to improving both the clinical decision
      making process in and management of this challenging group of patients. 

PMID- 24681141
TI  - Plasminogen regulates cardiac repair after myocardial infarction through its
      noncanonical function in stem cell homing to the infarcted heart.
AB  - OBJECTIVES: The purpose of this study was to investigate the role of plasminogen
      (Plg) in stem cell-mediated cardiac repair and regeneration after myocardial
      infarction (MI). BACKGROUND: An MI induces irreversible tissue damage, eventually
      leading to heart failure. Bone marrow (BM)-derived stem cells promote tissue
      repair and regeneration after MI. Thrombolytic treatment with Plg activators
      significantly improves the clinical outcome in MI by restoring cardiac perfusion.
      However, the role of Plg in stem cell-mediated cardiac repair remains unclear.
      METHODS: An MI was induced in Plg-deficient (Plg(-/-)) and wild-type (Plg(+/+))
      mice by ligation of the left anterior descending coronary artery. Stem cells were
      visualized by in vivo tracking of green fluorescent protein (GFP)-expressing BM
      cells after BM transplantation. Cardiac function, stem cell homing, and signaling
      pathways downstream of Plg were examined. RESULTS: Granulocyte colony-stimulating
      factor, a stem cell mobilizer, significantly promoted BM-derived stem cell
      (GFP(+)c-kit(+) cell) recruitment into the infarcted heart and stem cell-mediated
      cardiac repair in Plg(+/+) mice. However, Plg deficiency markedly inhibited stem
      cell homing and cardiac repair, suggesting that Plg is critical for stem cell
      mediated cardiac repair. Moreover, Plg regulated C-X-C chemokine receptor type 4
      (CXCR4) expression in stem cells in vivo and in vitro through matrix
      metalloproteinase-9. Lentiviral reconstitution of CXCR4 expression in BM cells
      successfully rescued stem cell homing to the infarcted heart in Plg-deficient
      mice, indicating that CXCR4 has a critical role in Plg-mediated stem cell homing
      after MI. CONCLUSIONS: These findings have identified a novel role for Plg in
      stem cell-mediated cardiac repair after MI. Thus, targeting Plg may offer a new
      therapeutic strategy for stem cell-mediated cardiac repair after MI.

PMID- 24681143
TI  - Survival differences in pediatric pulmonary arterial hypertension: clues to a
      better understanding of outcome and optimal treatment strategies.
AB  - OBJECTIVES: In order to describe survival and treatment strategies in pediatric
      pulmonary arterial hypertension (PAH) in the current era of PAH-targeted drugs
      and to identify predictors of outcome, we studied uniformly defined contemporary
      patient cohorts at 3 major referral centers for pediatric PAH (New York [NY],
      Denver, and the Netherlands [NL]). BACKGROUND: In pediatric PAH, discrepancies
      exist in reported survival rates between North American and European patient
      cohorts, and robust data for long-term treatment effects are lacking. METHODS:
      According to uniform inclusion criteria, 275 recently diagnosed consecutive
      pediatric PAH patients who visited the 3 referral centers between 2000 and 2010
      were included. RESULTS: Unadjusted survival rates differed between the center
      cohorts (1-, 3-, and 5-year transplantation-free survival rates: 100%, 96%, and
      90% for NY; 95%, 87%, and 78% for Denver; and 84%, 71%, and 62% for NL,
      respectively; p < 0.001). Based on World Health Organization (WHO) functional
      class and hemodynamic parameters, disease severity at diagnosis differed between
      the center cohorts. Adjustment for diagnosis, WHO functional class, indexed
      pulmonary vascular resistance, and pulmonary-to-systemic arterial pressure ratio
      resolved the observed survival differences. Treatment with PAH-targeted dual and
      triple therapy during the study period was associated with better survival than
      treatment with PAH-targeted monotherapy. CONCLUSIONS: Survival rates of pediatric
      PAH patients differed between 3 major referral centers. This could be explained
      by differences between the center cohorts in patients' diagnoses and measures of
      disease severity, which were identified as important predictors of outcome. In
      this study, treatment with PAH-targeted combination therapy during the study
      period was independently associated with improved survival.

PMID- 24681142
TI  - Insights into echo-attenuated plaques, echolucent plaques, and plaques with
      spotty calcification: novel findings from comparisons among intravascular
      ultrasound, near-infrared spectroscopy, and pathological histology in 2,294 human
      coronary artery segments.
AB  - OBJECTIVES: Three intravascular ultrasound (IVUS) signatures have been associated
      with coronary artery disease instability: echo attenuation, an intraplaque
      echolucent zone, and spotty calcification. The aim of this study was to
      investigate the substrates responsible for these IVUS signatures in a relatively
      large series of post-mortem human coronary samples. BACKGROUND: The exact
      mechanisms and pathological correlates underlying echo attenuation, an
      intraplaque echolucent zone, and spotty calcification remain poorly understood.
      METHODS: IVUS was compared with near-infrared spectroscopic detection of lipid
      core plaque and histopathology in 2,294 vessel segments from 151 coronary
      specimens from 62 patients at necropsy using the modified American Heart
      Association classification. RESULTS: IVUS detected echo-attenuated plaques in
      18.3% of segments, echolucent plaques in 10.5% of segments, and spotty
      calcification in 14.4% of segments. Histopathologically, 91.4% of echo-attenuated
      plaques corresponded to either a fibroatheroma (FA) with a necrotic core (NC) or
      pathological intimal thickening with a lipid pool; almost all segments with
      superficial echo attenuation indicated the presence of an FA with an advanced NC.
      Echolucent plaques indicated the presence of a relatively smaller lipid or NC
      compared with echo-attenuated plaques (thickness: 0.51 mm [interquartile range
      (IQR): 0.35 to 0.64 mm] vs. 0.70 mm [IQR: 0.54 to 0.92 mm] [p < 0.001]; arc: 74.5
      degrees  [IQR: 59.0 degrees  to 101.0 degrees ] vs. 90 degrees  [IQR: 70.0
      degrees  to 112.0 degrees ] [p < 0.001]), although 82.8% of superficial
      echolucent zones indicated an NC-containing FA. IVUS spotty calcification,
      especially when superficial in location (72.6%), was often associated with an FA
      with calcium deposits and had smaller arcs of calcium in the setting of FA
      compared with fibrocalcific plaques (37.5 degrees  [IQR: 23.0 degrees  to 53.0
      degrees ] vs. 59.0 degrees  [IQR: 46.0 degrees  to 69.0 degrees ]; p < 0.001).
      Comparisons between IVUS and near-infrared spectroscopy revealed that echo
      attenuated plaques contained the highest probability of near-infrared
      spectroscopy-derived lipid core plaque, followed by echolucent plaques and spotty
      calcifications. CONCLUSIONS: This study demonstrated that echo-attenuated plaque,
      especially superficial echo attenuation, was the most reliable IVUS signature for
      identifying a high-risk plaque (i.e., an FA containing a large NC).

PMID- 24681144
TI  - Drug-induced brugada syndrome in children: clinical features, device-based
      management, and long-term follow-up.
AB  - OBJECTIVES: The goal of this study was to investigate the clinical features,
      management, and long-term follow-up of children with drug-induced Brugada
      syndrome (BS). BACKGROUND: Patients with BS <12 years of age with a spontaneous
      type I electrocardiogram have a higher risk of arrhythmic events. Data on drug
      induced BS in patients <12 years of age are lacking. METHODS: Among 505 patients
      with ajmaline-induced BS, subjects <=12 years of age at the time of diagnosis
      were considered as children and eligible for this study. RESULTS: Forty children
      (60% male; age 8 +/- 2.8 years) were included. Twenty-four children (60%) had a
      family history of sudden death. Two (5%) had a previous episode of aborted sudden
      death, and 8 (20%) had syncope. Children experienced more frequent episodes of
      sinus node dysfunction (SND) compared with older subjects (7.5% vs. 1.5%; p =
      0.04) and had a comparable incidence of atrial tachyarrhythmias. Children more
      frequently experienced episodes of ajmaline-induced sustained ventricular
      arrhythmias (VAs) compared with older patients (10.0% vs. 1.3%; p = 0.005).
      Twelve children (30%) received an implantable cardioverter-defibrillator (ICD).
      After a mean follow-up time of 83 +/- 51 months, none of the children died
      suddenly. Spontaneous sustained VAs were documented in 1 child (2%). Among
      children with ICD, 1 (8%) experienced an appropriate shock, 4 (33%) had
      inappropriate ICD shocks, and 4 (33%) experienced device-related complications.
      CONCLUSIONS: Drug-induced BS is associated with atrial arrhythmias and SND.
      Children are at higher risk of ajmaline-induced VAs. The rate of device-related
      complications, leading to lead replacement or inappropriate shocks, is
      considerable and even higher than with appropriate interventions. Based on these
      findings, the optimal management of BS in childhood should remain individualized,
      taking into consideration the patient's clinical history and family's wishes.

PMID- 24681145
TI  - Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic
      dysfunction through proinflammatory effects and endothelial-mesenchymal
      transition.
AB  - OBJECTIVES: This study sought to investigate the effect of endothelial
      dysfunction on the development of cardiac hypertrophy and fibrosis. BACKGROUND:
      Endothelial dysfunction accompanies cardiac hypertrophy and fibrosis, but its
      contribution to these conditions is unclear. Increased nicotinamide adenine
      dinucleotide phosphate oxidase-2 (NOX2) activation causes endothelial
      dysfunction. METHODS: Transgenic mice with endothelial-specific NOX2
      overexpression (TG mice) and wild-type littermates received long-term angiotensin
      II (AngII) infusion (1.1 mg/kg/day, 2 weeks) to induce hypertrophy and fibrosis.
      RESULTS: TG mice had systolic hypertension and hypertrophy similar to those seen
      in wild-type mice but developed greater cardiac fibrosis and evidence of isolated
      left ventricular diastolic dysfunction (p < 0.05). TG myocardium had more
      inflammatory cells and VCAM-1-positive vessels than did wild-type myocardium
      after AngII treatment (both p < 0.05). TG microvascular endothelial cells (ECs)
      treated with AngII recruited 2-fold more leukocytes than did wild-type ECs in an
      in vitro adhesion assay (p < 0.05). However, inflammatory cell NOX2 per se was
      not essential for the profibrotic effects of AngII. TG showed a higher level of
      endothelial-mesenchymal transition (EMT) than did wild-type mice after AngII
      infusion. In cultured ECs treated with AngII, NOX2 enhanced EMT as assessed by
      the relative expression of fibroblast versus endothelial-specific markers.
      CONCLUSIONS: AngII-induced endothelial NOX2 activation has profound profibrotic
      effects in the heart in vivo that lead to a diastolic dysfunction phenotype.
      Endothelial NOX2 enhances EMT and has proinflammatory effects. This may be an
      important mechanism underlying cardiac fibrosis and diastolic dysfunction during
      increased renin-angiotensin activation.

PMID- 24681147
TI  - B-type natriuretic peptide in aortic stenosis: new insight in the era of
      biomarkers?

PMID- 24681146
TI  - 2013 ACC/AHA cholesterol treatment guideline: what was done well and what could
      be done better.
AB  - Five years after convening the expert panel, the 2013 ACC/AHA Guideline on the
      Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in
      Adults was released. The American College of Cardiology and American Heart
      Association issued the guideline on the basis of a systematic review of
      cholesterol treatment trials performed by the National Heart, Lung, and Blood
      Institute. This report critically appraises the guideline and provides our view
      of what was done well and what could be done better. In particular, we propose
      that the guideline succeeds in prioritizing statin therapy, expanding the focus
      to atherosclerotic cardiovascular disease (including stroke), and emphasizing
      absolute cardiovascular risk to determine eligibility for statin therapy. We
      contend that the guideline could be enhanced by refining the use of lipid goals
      rather than removing them, enhancing guidance on evaluation of cholesterol, and
      broadening the concept of age underpinning risk-based decision making to include
      vascular and physiological age. We further suggest that the next guideline panel
      could comprehensively review current best evidence, build on existing guidelines,
      and cultivate broader national and international consensus. Overall, we aim to
      continue discussions about the important contributions and shortfalls of the
      guideline and create momentum for effective implementation and timely updates. 

PMID- 24681148
TI  - Coronary computed tomography angiography for the detection of cardiac allograft
      vasculopathy: a meta-analysis of prospective trials.
AB  - OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of coronary
      computed tomography angiography (CCTA) for detecting cardiac allograft
      vasculopathy (CAV) in comparison with conventional coronary angiography (CCAG)
      alone or with intravascular ultrasound (IVUS). BACKGROUND: CAV limits long-term
      survival after heart transplantation, and screening for CAV is performed on
      annual basis. CCTA is currently not recommended for CAV screening due to the
      limited accuracy reported by early studies. Technological advances, however,
      might have resulted in improved test performance and might justify re-evaluation
      of this recommendation. METHODS: A systematic review of Medline, Cochrane, and
      Embase for all prospective trials assessing CAV using CCTA was performed using a
      standard approach for meta-analysis for diagnostic test and a bivariate analysis.
      RESULTS: Thirteen studies evaluating 615 patients (mean age 52 years, 83% male)
      and 9,481 segments fulfilled inclusion criteria. Patient-based analyses comparing
      CCTA versus CCAG for the detection of any CAV (> luminal irregularities) and
      significant CAV (stenosis >=50%), showed mean weighted sensitivities of 97% and
      94%, specificities of 81% and 92%, a negative predictive value (NPV) of 97% and
      99%, a positive predictive value (PPV) of 78% and 67%, and diagnostic accuracies
      of 88% and 94%, respectively. There was a strong trend toward improved
      sensitivity (97% vs. 91%, p = 0.06) and NPV (99% vs. 97%, p = 0.06) to detect
      significant CAV with 64-slice compared with 16-slice CCTA. A patient-based
      analysis of 64-slice CCTA versus IVUS showed a mean weighted sensitivity and
      specificity of 81% and 75% to detect CAV (intimal thickening >0.5 mm), whereas
      the PPV and NPV were 93% and 50%, respectively. CONCLUSIONS: CCTA using currently
      available technology is a reliable noninvasive imaging alternative to coronary
      angiography with an excellent sensitivity, specificity, and NPV for the detection
      of CAV.

PMID- 24681149
TI  - Coronary computed tomography angiography: is it time to replace the conventional
      coronary angiogram in heart transplant patients?

PMID- 24681150
TI  - Learning more from the dabigatran concentrations in the RE-LY study.

PMID- 24681151
TI  - Parental behavior correlates to baseline corticosterone of mates and offspring in
      nesting eastern bluebirds (Sialia sialis).
AB  - Raising nestlings in a biparental species involves a complex and dynamic
      interaction of physiology and behavior among a group of organisms. Parents may be
      predicted to vary their behaviors based not only upon their own state, but also
      in relation to the states of both offspring and the other parent. In this study
      we explore the relationships between parental feeding behaviors and family member
      condition in eastern bluebirds, with a special emphasis on baseline
      corticosterone, a hormone associated with energy mediation and stress. We found
      that the overall number of feeding trips made by both male and female parents
      were positively correlated to the corticosterone levels of nestlings. Maternal,
      but not paternal, baseline corticosterone levels were positively correlated to
      nestling baseline corticosterone levels. Additionally, adult males' feeding
      behavior was positively correlated to adult females' baseline corticosterone
      levels. These findings suggest a complex interplay between parental behavior and
      physiological state not only within a given organism, but also across organisms
      operating within a family unit. In addition, these results provide evidence that
      paternal and maternal efforts are influenced by related but distinct pressures,
      and that male and female parenting may be governed differentially even in species
      with relatively equitable biparental care.

PMID- 24681152
TI  - Environmental acidification is not associated with altered plasma corticosterone
      levels in the stream-side salamander, Desmognathus ochrophaeus.
AB  - As environments become increasingly altered due to anthropogenic factors,
      interest is growing in how endocrine systems respond to pollution and
      environmental degradation. Glucocorticoid hormones (GCs) are a type of stress
      hormones that are released upon activation of the hypothalamic-pituitary-adrenal
      axis and have widespread effects throughout the body. We tested the hypothesis
      that exposure to environmental acidification is associated with altered levels of
      plasma GCs in adult, stream-side Allegheny Mountain dusky salamanders
      (Desmognathus ochrophaeus). We compared plasma corticosterone (CORT) in
      salamanders living in 9 streams that differed in pH. Although capture and
      handling induced a robust increase in plasma CORT in all populations of
      salamanders, we discerned no significant effect of environmental pH on baseline
      CORT or handling-induced CORT levels. In a laboratory study, low pH decreased
      salamander locomotory activity compared to acid-neutral controls, but there was
      no effect of pH on plasma CORT. Decreased locomotory activity is a common
      amphibian response to stress, indicating that low pH has adverse effects on
      Allegheny Mountain dusky salamanders. Overall, we conclude that the effects of
      environmental pH on salamander behavior and other potential responses are not
      mediated by changes in plasma CORT levels. We discuss alternative explanations
      for our results and describe difficulties involved in searching for relationships
      between plasma GCs and environmental degradation.

PMID- 24681153
TI  - Nanosheet Au/Co3O4-based ultrasensitive nonenzymatic immunosensor for melanoma
      adhesion molecule antigen.
AB  - Highly sensitive and enzyme-free detection of melanoma adhesion molecule antigen
      (CD146) remains a challenge in clinical diagnosis. The prepared immunosensor,
      based on amination graphene (GS-NH2) and mesoporous nano-Co3O4 sheet combined
      with gold nanoparticles (Au/Co3O4), exhibited significantly increased electron
      transfer, high sensitivity and stability to CD146. Au/Co3O4 can increase the
      contact surface between the antibody and Au nanoparticles attached on Co3O4 than
      mesoporous Co3O4 only. And the mesoporous Co3O4 nanosheet can capture more
      biomolecules to enhance the sensitivity due to the large effective specific area.
      Amperometric i-t curve and electrochemical impedance spectroscopy (EIS) were used
      to characterize the recognition of CD146. This novel immunosensor, works well
      over a broad linear range of 0.01-15ng/mL, with a low detection limit of 3.4pg/mL
      (S/N=3). The immunosensor was evaluated for the determination of human serum
      sample, and received a satisfactory result. The developed immunosensor provides a
      promising approach for clinical research and diagnostic applications. 

PMID- 24681154
TI  - Carbon nanodots-chitosan composite film: a platform for protein immobilization,
      direct electrochemistry and bioelectrocatalysis.
AB  - A novel composite film based on carbon nanodots (CNDs) and chitosan was readily
      prepared and used as immobilization matrix to entrap a heme protein, hemoglobin
      (Hb) for direct electrochemistry and bioelectrocatalysis. A modified electrode
      was obtained by casting Hb-CNDs-chitosan composites on the glassy carbon (GC)
      electrode surface. Spectroscopic and electrochemical studies showed that Hb
      entrapped in the composite film remained in its native structures, and CNDs in
      the film can greatly facilitate DET between the protein and the GC electrode. The
      electron-transfer kinetics of Hb in composite film was qualitatively evaluated by
      using the Marcus theory, and the apparent heterogeneous electron-transfer rate
      constant (ks) was estimated to be 2.39(+/-0.03)s(-1) with Laviron equations. The
      modified electrode showed excellent electrocatalytic behavior to the substrate,
      hydrogen peroxide (H2O2). The linear current response for H2O2 was from 1*10(-6)
      to 1.18*10(-4)M with a detection limit of 0.27(+/-0.02)MUM at the signal-to-noise
      ratio of 3, and the apparent Michaelis-Menten constant was 0.067(+/-0.02)mM.
      These important features of CNDs-chitosan film have implied to be a promising
      platform for elaborating bioelectrochemical devices such as biosensors and
      biofuel cells. 

PMID- 24681155
TI  - Decreased spinal synaptic inputs to phrenic motor neurons elicit localized
      inactivity-induced phrenic motor facilitation.
AB  - Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since
      even brief disruption in phrenic neural activity is detrimental to life, on-going
      neural activity may play a key role in shaping phrenic motor output. To test the
      hypothesis that spinal mechanisms sense and respond to reduced phrenic activity,
      anesthetized, ventilated rats received micro-injections of procaine in the C2
      ventrolateral funiculus (VLF) to transiently (~30min) block axon conduction in
      bulbospinal axons from medullary respiratory neurons that innervate one phrenic
      motor pool; during procaine injections, contralateral phrenic neural activity was
      maintained. Once axon conduction resumed, a prolonged increase in phrenic burst
      amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity
      induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor
      alpha (TNFalpha) and atypical PKC (aPKC) activity in spinal segments containing
      the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for
      spinal TNFalpha and aPKC in iPMF following unilateral axon conduction block. A
      small phrenic burst amplitude facilitation was also observed contralateral to
      axon conduction block, indicating crossed spinal phrenic motor facilitation
      (csPMF). csPMF was independent of spinal TNFalpha and aPKC. Ipsilateral iPMF and
      csPMF following unilateral withdrawal of phrenic synaptic inputs were associated
      with proportional increases in phrenic responses to chemoreceptor stimulation
      (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These
      data suggest that local, spinal mechanisms sense and respond to reduced synaptic
      inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent
      compensatory mechanisms that assure adequate motor output is maintained in a
      physiological system in which prolonged inactivity ends life. 

PMID- 24681156
TI  - Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain
      injury and associated cognitive deficits.
AB  - Neuroinflammation is a component of secondary injury following traumatic brain
      injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent,
      pro-inflammatory lipid mediators generated from membrane phospholipids. In the
      absence of injury, leukotrienes are undetectable in the brain, but after trauma
      they are rapidly synthesized by a transcellular event involving infiltrating
      neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK
      886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking
      leukotriene synthesis, secondary brain damage, synaptic dysfunction, and
      cognitive impairments after TBI. Male Sprague Dawley rats (9-11weeks) received
      either MK-886 or vehicle after they were subjected to unilateral moderate fluid
      percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors
      for TBI. MK-886 was also administered before FPI to determine the preventative
      potential of FLAP inhibitors. MK-886 given before or after injury significantly
      blocked the production of leukotrienes, measured by reverse-phase liquid
      chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain
      edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886
      significantly attenuated blood-brain barrier disruption in the CA1 hippocampal
      region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses.
      The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by
      fewer deficits in post-injury spatial learning and memory performance in the
      radial arm water maze (RAWM). These results indicate that leukotrienes contribute
      significantly to secondary brain injury and subsequent cognitive deficits. FLAP
      inhibitors represent a novel anti-inflammatory approach for treating human TBI
      that is feasible for both intervention and prevention of brain injury and
      neurologic deficits. 

PMID- 24681157
TI  - The effect of diet on the protective action of D156844 observed in spinal
      muscular atrophy mice.
AB  - Spinal muscular atrophy (SMA) is an early-onset motor neuron disease
      characterized by loss of spinal motor neurons which leads to skeletal muscle
      atrophy. Proximal SMA results from the loss or mutation of the survival motor
      neuron (SMN) gene. In humans, the SMN gene is duplicated to produce two nearly
      identical genes, SMN1 and SMN2. SMN1 is lost in SMA but SMN2 is retained; in
      fact, the number of SMN2 copies correlates with disease severity. The SMN2
      inducer D156844 increases the survival and improves phenotype of SMN?7 SMA mice.
      Maternal diet also modifies the survival and phenotype of these mice. In this
      study, we show the effect of maternal diet on the protective effects of D156844
      in SMN?7 SMA mice. SMA mice maintained on the PicoLab20 Mouse diet survived
      longer when treated with D156844; the effect of diet was additive to the effect
      of D156844 on these mice. Brain levels of D156844 were higher in neonatal mice
      maintained on the PicoLab20 diet than those on the Harlan-Teklad 22/5 diet. SMN
      protein levels in the spinal cord were modestly elevated in D156844-treated,
      PicoLab20-maintained SMA mice. These data show that maternal diet does influence
      the responsiveness of D156844 in neonatal SMN?7 SMA mice. 

PMID- 24681158
TI  - The interplay between microRNAs and histone deacetylases in neurological
      diseases.
AB  - Neurological conditions, such as Alzheimer's disease and stroke, represent a
      prevalent group of devastating illnesses with few treatments. Each of these
      diseases or conditions is in part characterized by the dysregulation of many
      genes, including those that code for microRNAs (miRNAs) and histone deacetylases
      (HDACs). Recently, a complex relationship has been uncovered linking miRNAs and
      HDACs and their ability to regulate one another. This provides a new avenue for
      potential therapeutics as the ability to reinstate a careful balance between
      miRNA and HDACs has lead to improved outcomes in a number of in vitro and in vivo
      models of neurological conditions. In this review, we will discuss recent
      findings on the interplay between miRNAs and HDACs and its implications for
      pathogenesis and treatment of neurological conditions, including amyotrophic
      lateral sclerosis, Alzheimer's disease, Huntington's disease and stroke. 

PMID- 24681159
TI  - New red-fluorescent calcium indicators for optogenetics, photoactivation and
      multi-color imaging.
AB  - Most chemical and, with only a few exceptions, all genetically encoded
      fluorimetric calcium (Ca(2+)) indicators (GECIs) emit green fluorescence. Many of
      these probes are compatible with red-emitting cell- or organelle markers. But the
      bulk of available fluorescent-protein constructs and transgenic animals
      incorporate green or yellow fluorescent protein (GFP and YFP respectively). This
      is, in part, not only heritage from the tendency to aggregate of early-generation
      red-emitting FPs, and due to their complicated photochemistry, but also resulting
      from the compatibility of green-fluorescent probes with standard instrumentation
      readily available in most laboratories and core imaging facilities. Photochemical
      constraints like limited water solubility and low quantum yield have contributed
      to the relative paucity of red-emitting Ca(2+) probes compared to their green
      counterparts, too. The increasing use of GFP and GFP-based functional reporters,
      together with recent developments in optogenetics, photostimulation and super
      resolution microscopies, has intensified the quest for red-emitting Ca(2+)
      probes. In response to this demand more red-emitting chemical and FP-based Ca(2+)
      sensitive indicators have been developed since 2009 than in the thirty years
      before. In this topical review, we survey the physicochemical properties of these
      red-emitting Ca(2+) probes and discuss their utility for biological Ca(2+)
      imaging. Using the spectral separability index Xijk (Oheim M., 2010. Methods in
      Molecular Biology 591: 3-16) we evaluate their performance for multi-color
      excitation/emission experiments, involving the identification of morphological
      landmarks with GFP/YFP and detecting Ca(2+)-dependent fluorescence in the red
      spectral band. We also establish a catalog of criteria for evaluating Ca(2+)
      indicators that ideally should be made available for each probe. This article is
      part of a Special Issue entitled: Calcium signaling in health and disease. Guest
      Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and
      Marc Moreau. 

PMID- 24681160
TI  - Architecture and assembly of the Type VI secretion system.
AB  - The Type VI secretion system (T6SS) delivers protein effectors to diverse cell
      types including prokaryotic and eukaryotic cells, therefore it participates in
      inter-bacterial competition and pathogenesis. The T6SS is constituted of an
      envelope-spanning complex anchoring a cytoplasmic tubular edifice. This tubular
      structure is evolutionarily, functionally and structurally related to the tail of
      contractile phages. It is composed of an inner tube tipped by a spike complex,
      and engulfed within a sheath-like structure. This structure assembles onto a
      platform called "baseplate" that is connected to the membrane sub-complex. The
      T6SS functions as a nano-crossbow: upon contraction of the sheath, the inner tube
      is propelled towards the target cell, allowing effector delivery. This review
      focuses on the architecture and biogenesis of this fascinating secretion machine,
      highlighting recent advances regarding the assembly of the membrane or tail
      complexes. This article is part of a Special Issue entitled: Protein trafficking
      and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. 

PMID- 24681161
TI  - Can rats solve the active place avoidance task without the room-bound cues?
AB  - The active place avoidance task is used in the research of spatial cognition.
      Rats are trained on a rotating arena to avoid an aversive stimulus delivered in a
      part of the room while being transported toward it by the arena rotation. The
      task tests the ability of rats to navigate with respect to distal cues in the
      room and to ignore confusing cues on the arena. The demand for cue segregation
      makes the task suitable for studying neural mechanisms responsible for cognitive
      coordination. An incidental observation made in our laboratory implied that
      overtrained rats may be able to solve the task without the room-bound cues. The
      aim of this study was to test this observation. The room-bound cues were hidden
      by switching off the lights. Rats trained only in darkness did not learn the task
      at all. Rats that were initially pre-trained in light performed considerably
      better. In a few exceptional dark sessions they even reached the level of
      performance observed in light. The rats needed the aversive stimuli to keep off
      the to-be-avoided sector. Without them, they continued their behavior, but with
      no spatial relationship to the to-be-avoided sector. We conclude that rats are
      able to solve the place avoidance task without the room-bound cues, but not as
      efficiently as in their presence. 

PMID- 24681162
TI  - Central injection of relaxin-3 receptor (RXFP3) antagonist peptides reduces
      motivated food seeking and consumption in C57BL/6J mice.
AB  - Behavioural arousal in mammals is regulated by various interacting central
      monoamine- and peptide-neurotransmitter/receptor systems, which function to
      maintain awake, alert and active states required for performance of goal-directed
      activities essential for survival, including food seeking. Existing anatomical
      and functional evidence suggests the highly-conserved neuropeptide, relaxin-3,
      which signals via its cognate Gi/o-protein coupled receptor, RXFP3, contributes
      to behavioural arousal and feeding behaviour in rodents. In studies to
      investigate this possibility further, adult male C57BL/6J mice were treated with
      the selective RXFP3 antagonist peptides, R3(B1-22)R/I5(A) and R3(B1-22)R, and
      motivated food seeking and consumption was assessed as a reflective output of
      behavioural arousal. Compared to vehicle treatment, intracerebroventricular (icv)
      injection of RXFP3 antagonists reduced: (i) food anticipatory activity before
      meal time during food restriction; (ii) consumption of highly palatable food;
      (iii) consumption of regular chow during the initial dark phase, and; (iv)
      consumption of regular chow after mild (~4-h) food deprivation. Effects were not
      due to sedation and appeared to be specifically mediated via antagonism of
      relaxin-3/RXFP3 signalling, as RXFP3 antagonist treatment did not alter locomotor
      activity in wild-type mice or reduce palatable food intake in relaxin-3 deficient
      (knock-out) mice. Notably, in contrast to similar studies in the rat, icv
      injection of RXFP3 agonists and infusion into the paraventricular hypothalamic
      nucleus did not increase food consumption in mice, suggesting species differences
      in relaxin-3/RXFP3-related signalling networks. Together, our data provide
      evidence that endogenous relaxin-3/RXFP3 signalling promotes motivated food
      seeking and consumption, and in light of the established biological and
      translational importance of other arousal systems, relaxin-3/RXFP3 networks
      warrant further experimental investigation. 

PMID- 24681163
TI  - Isolation and characterization of Xenopus soluble epoxide hydrolase.
AB  - Soluble epoxide hydrolase (sEH) contributes to cell growth, but the contribution
      of sEH to embryonic development is not well understood. In this study, Xenopus
      sEH cDNA was isolated from embryos of Xenopus laevis. The Xenopus sEH was
      expressed in Escherichia coli and was purified. The epoxide hydrolase and
      phosphatase activities of purified sEH were investigated. The Xenopus sEH did not
      show phosphatase activity toward 4-methylumbelliferyl phosphate or several
      lysophosphatidic acids although it had EH activity. The amino acid sequence of
      Xenopus sEH was compared with that reported previously. We found amino acid
      substitutions of the 29th Thr to Asn and the 146th Arg to His and prepared a sEH
      mutant (N29T/H146R), designed as mutant 1. Neither wild-type sEH nor mutant 1 had
      phosphatase activity. Additional substitution of the 11th Gly with Asp was found
      by comparison with human sEH which has phosphatase activity, but the Xenopus sEH
      mutant G11D prepared as mutant 2 did not have phosphatase activity. The epoxide
      hydrolase activity of sEH seemed to be similar to that of human sEH, while
      Xenopus sEH did not have phosphatase activity toward several substrates that
      human sEH metabolizes. 

PMID- 24681164
TI  - miR-17 is involved in the regulation of LC-PUFA biosynthesis in vertebrates:
      effects on liver expression of a fatty acyl desaturase in the marine teleost
      Siganus canaliculatus.
AB  - Biosynthesis in vertebrates of long-chain polyunsaturated fatty acids (LC-PUFA)
      such as arachidonic (ARA; 20:4n-6), eicosapentaenoic (EPA; 20:5n-3) and
      docosahexaenoic (DHA; 22:6n-3) acids requires the catalysis by fatty acyl
      desaturases (Fads). A vertebrate Fad with Delta4 activity catalyzing the direct
      conversion of 22:5n-3 to DHA was discovered in the marine teleost rabbitfish
      Siganus canaliculatus. Recent studies in vertebrates have shown that miRNAs may
      participate in the regulation of lipid metabolism at post-transcription level.
      However, their roles in LC-PUFA biosynthesis were not known. In the present
      study, in silico analysis predicts that the rabbitfish Delta4 Fad may be a target
      of miR-17 and thus we cloned miR-17, which is located at the forepart of the miR
      17-92 cluster. Dual luciferase reporter assays demonstrated that miR-17 targeted
      the 3'UTR of Delta4 Fad directly. Furthermore, the expression level of miR-17
      displayed an inverse pattern with that of Delta4 Fad mRNA in gill, liver and
      eyes, and also the Delta4 Fad protein quantity in rabbitfish liver. Incubation of
      rabbitfish primary hepatocytes with linoleic acid (LA; 18:2n-6), alpha-linolenic
      acid (LNA; 18:3n-3), EPA or DHA showed differential effects on miR-17, Delta4 Fad
      and Delta6/Delta5 Fad expression. LNA promoted the expression of miR-17 and
      Delta6/Delta5 Fad, but suppressed the expression of Delta4 Fad. In contrast, LA
      and EPA decreased the expression of miR-17 and Delta6/Delta5 Fad, but had no
      effect on Delta4 Fad. However, all the above were down-regulated by DHA. These
      data indicate that miR-17 was involved in the regulation of LC-PUFA biosynthesis
      in rabbitfish liver by targeting Delta4 Fad.

PMID- 24681166
TI  - Barbed suture vs traditional suture in single-port total laparoscopic
      hysterectomy.
AB  - STUDY OBJECTIVE: To compare surgical outcomes between barbed suture and
      traditional suture used in repair of the vaginal vault during single-port total
      laparoscopic hysterectomy (TLH). DESIGN: Case-control study (Canadian Task Force
      classification II-2). SETTING: Two institutions. PATIENTS: One hundred two
      patients with benign uterine disease. INTERVENTIONS: Single-port TLH using barbed
      suture (n = 43) or traditional suture (n = 59). MEASUREMENTS AND MAIN RESULTS:
      Patient characteristics (age, body mass index, demographic data), procedures
      performed, uterine weight, and uterine disease were similar between the 2 study
      groups. There were also no differences in operative complications, conversion to
      other surgical approaches, operative blood loss, postoperative pain, and duration
      of hospital stay between the 2 groups. Use of barbed suture significantly reduced
      the time required for vaginal cuff suturing (11.4 vs 22.5 minutes; p < .001), as
      well as total operative time (92.0 vs 105.2 minutes; p = .002). Use of barbed
      suture is less technically demanding than traditional suture (p < .001).
      CONCLUSION: Use of barbed suture in single-port TLH may aid surgeons by reducing
      operative time, suturing time, and surgical difficulty.

PMID- 24681165
TI  - A new monoclonal antibody, 4-1a, that binds to the amino terminus of human
      lipoprotein lipase.
AB  - Lipoprotein lipase (LPL) has been highly conserved through vertebrate evolution,
      making it challenging to generate useful antibodies. Some polyclonal antibodies
      against LPL have turned out to be nonspecific, and the available monoclonal
      antibodies (Mabs) against LPL, all of which bind to LPL's carboxyl terminus, have
      drawbacks for some purposes. We report a new LPL-specific monoclonal antibody,
      Mab 4-1a, which binds to the amino terminus of LPL (residues 5-25). Mab 4-1a
      binds human and bovine LPL avidly; it does not inhibit LPL catalytic activity nor
      does it interfere with the binding of LPL to heparin. Mab 4-1a does not bind to
      human hepatic lipase. Mab 4-1a binds to GPIHBP1-bound LPL and does not interfere
      with the ability of the LPL-GPIHBP1 complex to bind triglyceride-rich
      lipoproteins. Mab 4-1a will be a useful reagent for both biochemists and clinical
      laboratories. 

PMID- 24681167
TI  - Impact of myomas on the results of transcervical resection of the endometrium.
AB  - STUDY OBJECTIVE: To investigate long-term hysterectomy rates after transcervical
      resection of the endometrium (TCRE) performed by experienced surgeons in the
      presence and absence of intracavitary myomas. DESIGN: Multicenter case-control
      study (Canadian Task Force classification II-2). PATIENTS: The study group
      comprised 456 women with myomas who met the inclusion criteria, and of these, 82
      (17.98%) later underwent hysterectomy. The control group comprised 1438 women
      without myomas, and of these, 284 (19.75%) later underwent hysterectomy. METHODS:
      From 2001 to 2004, standardized results were extracted from Hyskobase on the
      basis of a total of 1894 women aged 23 to 59 years. The women were identified as
      having or not having myomas, and data from both groups were statistically
      analyzed. Detailed information on myoma size and intramural involvement (type 0,
      1, and 2) was collected. MEASUREMENTS AND MAIN RESULTS: After TCRE, women with
      type 2 myomas, compared with those with type 0 myomas, were found to have a
      significantly higher risk of undergoing hysterectomy (p = .04), and women,
      including controls, with myomas >3.6 cm in greatest diameter were found to have a
      significantly higher risk of undergoing hysterectomy than were those with smaller
      myomas (p = .01). There was no statistically significant difference in risk of
      hysterectomy between type 0 and type 1 myomas or between type 1 and type 2
      myomas. When hysterectomy rates between the myoma and control groups were
      compared, there was an increased risk of hysterectomy in the control group (p =
      .008). Multiple-step multivariate regression analysis of uterine and procedural
      characteristics of TCRE demonstrated that factors that were positive predictors
      of hysterectomy within 66 months after resection were younger age, inaccessible
      uterine corners, enlarged uterus, and pretreatment using gonadotropin-releasing
      hormone agonists. CONCLUSION: When performing TCRE in women with intracavitary
      myomas, the chance of treatment success is worsened if they are of type 2 or
      their diameter is >3.5 cm. In addition, younger age increases the risk of
      hysterectomy and the need for pretreatment with gonadotropin-releasing hormone
      agonists, or if the uterus is enlarged or the uterine corners are difficult to
      access during the procedure.

PMID- 24681168
TI  - Feasibility of resectoscopic operative hysteroscopy in a UK outpatient clinic
      using local anesthetic and traditional reusable equipment, with patient
      experiences and comparative cost analysis.
AB  - STUDY OBJECTIVE: To assess procedural success, patient acceptability, and cost
      saving potential of operative hysteroscopy using conventional equipment and local
      anesthetic in an outpatient clinic. DESIGN: Feasibility study/service evaluation
      (Canadian Task Force classification II-3). SETTING: Outpatient (office) clinic in
      a large UK teaching hospital. PATIENTS: One hundred eighteen women with diagnosed
      or suspected intrauterine myomas or polyps. INTERVENTIONS: Operative hysteroscopy
      (122 monopolar resection procedures using 8- or 10-mm diameter rigid
      resectoscopes with glycine solution for uterine irrigation) with the patient
      under local anesthesia in an outpatient (office) clinic. MEASUREMENTS AND MAIN
      RESULTS: Procedural success, duration of procedure, pathologic measurements,
      glycine irrigant deficit, patient pain scores and satisfaction, and comparative
      costs were recorded. Success of outpatient procedures was 90% (110 of 122
      attempted), with a significantly reduced median procedure duration compared with
      a surgical setting using local (-7 minutes; p = .009) or general (-12.5 minutes;
      p < .001) anesthetic. Glycine irrigant absorption was low (median deficit, 0 mL),
      and no deficit was observed in 81% of patients. Mean (SD) estimated disease
      volume was comparable to that of hysteroscopic resection procedures in a surgical
      setting (3.38 [5.09] cm(3)), and weight was 1.8 (1.84) g. Patients tolerated the
      procedure well and reported low pain scores (highest median periprocedure pain
      measurement was 1.25 of 10), and 7-day follow-up satisfaction responses were
      positive. Retrospective cost analysis demonstrated that operative resection in an
      outpatient clinic was less expensive than in a surgical setting using general
      anesthetic (-$1003) or local anaesthetic (-$234). Reduced staff costs were the
      primary reason for this saving. CONCLUSIONS: Operative hysteroscopic resection of
      myomas and polyps is feasible and well tolerated by patients in an
      outpatient/office setting using local anaesthetic and conventional equipment. The
      outpatient procedure is less expensive and its duration is shorter than in a
      surgical setting.

PMID- 24681169
TI  - Bone morphogenetic protein-4 inhibits adult neurogenesis and is regulated by
      fractone-associated heparan sulfates in the subventricular zone.
AB  - Fractones are extracellular matrix structures that display a fractal
      ultrastructure and that are visualized as puncta after immunolabeling for laminin
      or heparan sulfate proteoglycans. In the adult brain, fractones are found
      throughout the subventricular zone (SVZ). The role of fractones is just emerging.
      We have recently shown that fractones sequester fibroblast growth factor-2 and
      bone morphogenetic protein-7 from the brain ventricles to regulate cell
      proliferation in the SVZ of the lateral ventricle, the primary neural stem cell
      niche and neurogenic zone in adulthood. Here, we have examined in vivo the effect
      of bone morphogenetic protein-4 (BMP-4) on cell proliferation in the SVZ and we
      have determined whether BMP-4 interacts with fractones to promote this effect. To
      examine BMP-4 effect on cell proliferation, BMP-4 was intracerebroventricularly
      injected, and bromodeoxyuridine immunolabeling was performed on frozen sections
      of the adult mouse brain. To identify the location of BMP-4 binding, biotinylated
      BMP-4 was injected, and its binding localized post-mortem with streptavidin,
      Texas red conjugate. Injection of heparitinase-1 was used to desulfate fractones
      and determine whether the binding and the effect of BMP-4 on cell proliferation
      are heparan sulfate-dependent. BMP-4 inhibited cell proliferation in the SVZ
      neurogenic zone. Biotinylated-BMP-4 bound to fractones and some adjacent blood
      vessels. Co-injection of heparitinase-1 and biotinylated-BMP-4 resulted in the
      absence of signal for biotinylated-BMP-4, indicating that the binding was heparan
      sulfate dependent. Moreover, preventing the binding of BMP-4 to fractones by
      heparitinase-1 reinforced the inhibitory effect of BMP-4 on cell proliferation in
      the SVZ. These results show that BMP-4 inhibits cell proliferation in the SVZ
      neurogenic zone and that the binding of BMP-4 to fractone-associated heparan
      sulfates moderates this inhibitory effect. Together with our previous results,
      these data support the view that fractones capture growth factors and modulate
      their activity in the neural tissues lining the ventricles. 

PMID- 24681170
TI  - Sex hormone binding globulin in the rat olfactory system.
AB  - Ovarian steroids are known to act on the olfactory system. Their mode of action,
      however, is mostly unclear to date since nuclear receptors are lacking in sensory
      neurons. Here we used immunocytochemistry and RT-PCR to study expression and
      distribution of sex hormone binding globulin (SHBG) in the rat olfactory system.
      Single sensory cells in the olfactory mucosa and their projections in the
      olfactory bulb showed specific SHBG immunostaining as determined by double
      immunofluorescence with olfactory marker protein OMP. Larger groups of SHBG
      stained sensory cells occurred in the vomeronasal organ (VNO). A portion of the
      olfactory glomeruli in the accessory olfactory bulb showed large networks of SHBG
      positive nerve fibres. Some of the mitral cells showed SHBG immune fluorescence.
      RT-PCR revealed SHBG encoding mRNA in the olfactory mucosa, in the VNO and in the
      olfactory bulbs indicating intrinsic expression of the binding globulin. The VNO
      and its related projections within the limbic system are known to be sensitive to
      gonadal steroid hormones. We conclude that SHBG may be of functional importance
      for rapid effects of olfactory steroids on limbic functions including the control
      of reproductive behaviours through pheromones. 

PMID- 24681171
TI  - Remission from post-traumatic stress disorder in adults: a systematic review and
      meta-analysis of long term outcome studies.
AB  - Posttraumatic stress disorder (PTSD) is a frequent mental disorder associated
      with significant distress and high costs. We conducted the first systematic
      review and meta-analysis on spontaneous long-term remission rates, i. e., without
      specific treatment. Data sources were searches of databases, hand searches, and
      contact with authors. Remission estimates were obtained from observational
      prospective studies of PTSD without specific treatment. Remission was defined as
      the actual percentage of PTSD cases at baseline who are non-cases after a minimum
      of ten months. Forty-two studies with a total of 81,642 participants were
      included. The mean observation period was 40 months. Across all studies, an
      average of 44.0% of individuals with PTSD at baseline were non-cases at follow
      up. Remission varied between 8 and 89%. In studies with the baseline within the
      first five months following trauma the remission rate was 51.7% as compared to
      36.9% in studies with the baseline later than five months following trauma.
      Publications on PTSD related to natural disaster reported the highest mean of
      remission rate (60.0%), whereas those on PTSD related to physical disease
      reported the lowest mean of remission rate from PTSD (31.4%). When publications
      on natural disaster were used as a reference group, the only type of traumatic
      events to differ from natural disaster was physical disease. No other measured
      predictors were associated with remission from PTSD. Long-term remission from
      PTSD without specific treatment varies widely and is higher in studies with the
      baseline within five months following trauma.

PMID- 24681172
TI  - Reply: To PMID 23973920.

PMID- 24681173
TI  - Natural history of eosinophilic esophagitis in asymptomatic patients.

PMID- 24681174
TI  - Liver and atherosclerosis.

PMID- 24681175
TI  - Unusual complication of endoscopic cystogastrostomy.

PMID- 24681176
TI  - Reply: To PMID 23954315.

PMID- 24681177
TI  - Toll-like receptor 2 regulates intestinal inflammation by controlling integrity
      of the enteric nervous system: why were TLR3's roles not tested?

PMID- 24681178
TI  - A rare cause of epigastric pain and diarrhea.

PMID- 24681179
TI  - Preoperative intravenous parecoxib reduces length of stay on ambulatory
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The complexity of pain after laparoscopic cholecystectomy (LC) needs
      multi-module analgesia. Opioids are widely used for perioperative pain but
      associated with numerous adverse effects. We investigated the effect of parecoxib
      administrated preoperatively and postoperatively for analgesia after ambulatory
      laparoscopic cholecystectomy. METHODS: 120 patients scheduled for ambulatory LC
      with general anesthesia were randomly assigned to three groups: group A received
      40 mg parecoxib injection 30-45 min before anesthesia induction and 4 ml saline
      injection when gallbladder was removed; group B received 4 ml saline injection 30
      45 min before anesthesia induction and 40 mg parecoxib injection when gallbladder
      was removed; group C received 4 ml saline injection 30-45 min before anesthesia
      induction and the time when gallbladder was removed. We recorded the time achieve
      to modified Aldrete's score > 9 in the post-anesthesia care unit (PACU) and
      modified Post-Anesthetic Discharge Scoring System (PADSS) > 9 in ambulatory unit.
      The visual analog scale (VAS) was used to assess the degree of the postoperative
      pain in the first 24 h, and the numbers of patients who need additional analgesic
      and postoperative adverse effects were also recorded. RESULTS: Patients of group
      A had a shorter length of stay (LOS) in PACU compared to these of group B and
      group C (32.4 +/- 7.2 min vs. 39.1 +/- 10.4 min and 42.2 +/- 7.6 min, P < 0.05).
      Patients of group A also had a shorter discharge time compared to these of group
      B and group C (148.4 +/- 39.3 min vs. 187.9 +/- 47.7 min and 223.4 +/- 52.5 min,
      P < 0.05). Moreover, patients of group A experienced reduced pain intensity, less
      postoperative side effect, and less additional analgesic requirement. CONCLUSION:
      Preoperative administration of parecoxib for postoperative analgesia provided
      significant effect on reducing PACU length of stay (LOS) and discharge time, and
      improving patient outcome after ambulatory LC.

PMID- 24681181
TI  - Nail dystrophy mystery.

PMID- 24681180
TI  - Respiratory events in infants presenting with apparent life threatening events:
      is there an explanation from esophageal motility?
AB  - OBJECTIVE: To test the hypothesis that proximal aerodigestive clearance
      mechanisms mediated by pharyngoesophageal motility during spontaneous respiratory
      events (SREs) are distinct in infants with apparent life threatening events
      (ALTEs). STUDY DESIGN: Twenty infants (10 with proven ALTE, 10 healthy controls)
      had pharyngoesophageal manometry to investigate motility changes concurrent with
      respiratory events detected by respiratory inductance plethysmography and nasal
      thermistor methods. We measured changes in resting upper esophageal and lower
      esophageal sphincter pressures, esophageal peristalsis characteristics, and
      gastroesophageal reflux. Statistical analysis included mixed models; data
      presented as mean+/-SD, median (range), or percentage. RESULTS: Infants with ALTE
      (vs controls) had: (1) delays in restoring aerodigestive normalcy as indicated by
      more frequent (P=.03) and prolonged SREs (P<.01); (2) a lower magnitude of
      protective upper esophageal sphincter contractile reflexes (P=.01); (3)
      swallowing as the most frequent esophageal event associated with SREs (84%), with
      primary peristalsis as the most prominent aerodigestive clearance mechanism (64%
      vs 38%, P<.01); (4) a higher proportion of failed esophageal propagation (10% vs
      0%, P=.02); and (5) more frequent mixed apneic mechanisms (P<.01) and more
      gasping breaths (P=.04). CONCLUSIONS: In infants with ALTE, prolonged SREs are
      associated with ineffective esophageal motility characterized by frequent primary
      peristalsis and significant propagation failure, thus suggestive of dysfunctional
      regulation of swallow-respiratory junction interactions. Hence, treatment should
      not target gastroesophageal reflux, but rather the proximal aerodigestive tract.

PMID- 24681182
TI  - Smoking and arterial stiffness in youth with type 1 diabetes: the SEARCH
      Cardiovascular Disease Study.
AB  - OBJECTIVE: To evaluate the effects of smoking on early markers of cardiovascular
      disease (arterial stiffness) in adolescents with and without type 1 diabetes
      (T1D) in the SEARCH Cardiovascular Disease Study. STUDY DESIGN: Participants
      included 606 youth (18.9 +/- 3.3 years, 83% non-Hispanic white; 50% male). Six
      groups were defined: (1) smokers with T1D (n = 80); (2) former smokers with T1D
      (n = 88); (3) nonsmokers with T1D (n = 232); (4) smokers without T1D (n = 40);
      (5) former smokers without T1D former (n = 51); and (6) nonsmokers without T1D (n
      = 115). Arterial stiffness measurements included pulse wave velocity (PWV),
      augmentation index, and brachial distensibility. Multivariate linear regression
      was used to assess the independent and joint effects of T1D and smoking on
      arterial stiffness. RESULTS: Nearly 20% of both youth with and without T1D and
      T1D were smokers. In youth without T1D, smokers had higher trunk and arm PWV.
      After adjustment for potential confounders, T1D, but not smoking, was an
      independent predictor of PWV (P < .05). Moreover, smoking status did not modify
      the association between T1D and increased arterial stiffness. CONCLUSIONS: We
      found a high prevalence of smoking among youth with and without T1D; however,
      smoking status was not independently associated with increased arterial stiffness
      in youth with T1D.

PMID- 24681183
TI  - The effectiveness of the Geritalk communication skills course: a real-time
      assessment of skill acquisition and deliberate practice.
AB  - BACKGROUND: Communication skills are critical in Geriatrics and Palliative
      Medicine because these patients confront complex clinical scenarios. We evaluated
      the effectiveness of the Geritalk communication skills course by comparing pre-
      and post-course real-time assessment of the participants leading family meetings.
      We also evaluated the participants' sustained skills practice. MEASURES: We
      compare the participants' skill acquisition before and after Geritalk using a
      direct observation Family Meeting Communication Assessment Tool and assess their
      deliberate practice at follow-up. INTERVENTION: First-year Geriatrics or
      Palliative Medicine fellows at Mount Sinai Medical Center and the James J. Peters
      Bronx VA Medical Center participated in Geritalk. OUTCOMES: Pre- and post-course
      family meeting assessments were compared. An average net gain of 6.8 skills
      represented a greater than 20% improvement in use of applicable skills. At two
      month follow-up, most participants reported deliberate practice of fundamental
      and advanced skills. CONCLUSIONS/LESSONS LEARNED: This intensive training and
      family meeting assessment offers evidence-based communication skills training.

PMID- 24681184
TI  - Benzodiazepines.

PMID- 24681185
TI  - Time course of bronchial cell inflammation following exposure to diesel
      particulate matter using a modified EAVES.
AB  - Electrostatic deposition of particles onto the surface of well-differentiated
      airway cells is a rapid and efficient means to screen for toxicity associated
      with exposure to fine and ultrafine particulate air pollution. This work
      describes the development and application of an electrostatic aerosol in vitro
      exposure system (EAVES) with increased throughput and ease-of-use. The modified
      EAVES accommodates standard tissue culture plates and uses an alternating
      electric field to deposit a net neutral charge of aerosol onto air-interface cell
      cultures. Using this higher-throughput design, we were able to examine the time
      course (1, 3, 6, 9, and 24 h post-exposure) of transcript production and
      cytotoxicity in well-differentiated human bronchial cells exposed to diesel
      particulate matter at levels of 'real-world' significance. Statistically
      significant responses were observed at exposure levels (~0.4 MUg/cm(2)) much
      lower than typically reported in vitro using traditional submerged/resuspended
      techniques. Levels of HO-1, IL-8, CYP1A1, COX-2, and HSP-70 transcripts increased
      immediately following diesel particulate exposure and persisted for several
      hours; cytotoxicity was increased at 24h. The modified EAVES provides a platform
      for higher throughput, more efficient and representative testing of aerosol
      toxicity in vitro.

PMID- 24681186
TI  - Effects of fish oil with a high content of n-3 polyunsaturated fatty acids on
      mouse gut microbiota.
AB  - BACKGROUND AND AIMS: Many studies show that fish oil with high content of n-3
      polyunsaturated fatty acids (PUFAs) plays an important role in human health and
      disease. But the effects of fish oil with high content of PUFAs on gut
      microbiota, which are also known play a significant role in several human
      diseases, is not clear. In the present study we evaluated the effects of fish oil
      with high content of n-3 PUFAs on gut microbiota. METHODS: Changes in gut
      microbiota in ICR mice after supplementation of fish oil (containing
      eicosapentaenoic acid and docosahexaenoic acid: ~40 and 27% respectively) for 15
      days was characterized using the hypervariable V3 region of the 16 rRNA gene
      based polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis
      (DGGE) profiling, DNA sequencing, and phylogenetic analysis techniques. RESULTS:
      Fish oil treatment resulted in a decrease in Helicobacter, Uncultured bacterium
      clone WD2_aaf07d12 (GenBank: EU511712.1), Clostridiales bacterium,
      Sphingomonadales bacterium and Pseudomonas species Firmicutes, and several
      uncultured bacteria. CONCLUSIONS: Fish oil with a high content of n-3 PUFAs are
      capable of producing significant changes in the gut microbiota that may, at least
      in part, explain the health benefits or injury induced by fish oil use.

PMID- 24681187
TI  - (153)Sm-EDTMP for pain relief of bone metastases from prostate and breast cancer
      and other malignancies.
AB  - BACKGROUND AND AIMS: Approximately 85% of patients with cancer suffer severe
      metastatic bone pain for which radionuclide therapy has been employed for pain
      palliation. We undertook this study to evaluate the pain relief effect of (153)Sm
      EDTMP in Mexican patients with severe and painful bone metastases from mainly
      prostate, breast, and renal cancer and other malignancies. METHODS: Patients
      (277) with intense sustained pain caused by bone metastases were referred to the
      Nuclear Medicine Department of the Oncology Hospital of the Mexican Social
      Security Institute. The patients had to have acceptable physical conditions, a
      previous positive (99m)Tc-MDP scan and blood values within normal range. (153)Sm
      EDTMP was prepared at the Instituto Nacional de Investigaciones Nucleares (ININ)
      and 37 MBq/kg of body weight was injected intravenously. Pain palliation was
      evaluated with a visual analogue scale (VAS) and a verbal rating scale (VRS)
      before treatment and 3 and 12 weeks after treatment was started. RESULTS: The age
      interval of the patients was 24-92 years with a mean age of 64 +/- 12 years. Mean
      values for hemoglobin, leukocyte and platelet counts did not statistically differ
      at zero time, 3 and 12 weeks after treatment. Pain intensity and relief
      assessment were statistically different: 9.1 +/- 0.61 units initially; 4.2 +/-
      1.3 units 3 weeks later (54%) and after 12 weeks the pain diminished to 2.4 +/-
      1.4 units (74%) in the pain relief score scales. CONCLUSIONS: (153)Sm-EDTMP was
      readily available, safe and well tolerated. We conclude that (153)Sm-EDTMP was an
      adequate palliative agent and was the best option for our Mexican patients to
      relieve their severe metastatic bone pain.

PMID- 24681188
TI  - Coexistence of tethered cord syndrome, congenital lumbar fusion, and butterfly
      vertebra.

PMID- 24681189
TI  - The osmoregulatory effects of rearing Mozambique tilapia in a tidally changing
      salinity.
AB  - The native distribution of Mozambique tilapia, Oreochromis mossambicus, is
      characterized by estuarine areas subject to salinity variations between fresh
      water (FW) and seawater (SW) with tidal frequency. Osmoregulation in the face of
      changing environmental salinity is largely mediated through the neuroendocrine
      system and involves the activation of ion uptake and extrusion mechanisms in
      osmoregulatory tissues. We compared plasma osmolality, plasma prolactin (PRL),
      pituitary PRL mRNA, and mRNA of branchial ion pumps, transporters, channels, and
      PRL receptors in tilapia reared in FW, SW, brackish water (BW) and in tidally
      changing salinity, which varied between FW (TF) and SW (TS) every 6h. Plasma PRL
      was higher in FW tilapia than in SW, BW, TF, and TS tilapia. Unlike tilapia
      reared in FW or SW, fish in salinities that varied tidally showed no correlation
      between plasma osmolality and PRL. In FW fish, gene expression of PRL receptor 1
      (PRLR1), Na(+)/Cl(-) cotransporter (NCC), aquaporin 3 (AQP3) and two isoforms of
      Na(+)/K(+)-ATPase (NKA alpha1a and NKA alpha1b) was higher than that of SW, BW or
      tidally-changing salinity fish. Gene expression of the Na(+)/K(+)/2Cl(-)
      cotransporter (NKCC1a), and the cystic fibrosis transmembrane conductance
      regulator (CFTR) were higher in fish in SW, BW or a tidally-changing salinity
      than in FW fish. Immunocytochemistry revealed that ionocytes of fish in tidally
      changing salinities resemble ionocytes of SW fish. This study indicated that
      tilapia reared in a tidally-changing salinity can compensate for large changes in
      external osmolality while maintaining osmoregulatory parameters within a narrow
      range closer to that observed in SW-acclimated fish. 

PMID- 24681190
TI  - Castration affects reproductive but not aggressive behavior in a cichlid fish.
AB  - Gonads are the main source of sex steroids, which have been implicated in the
      regulation of sexually differentiated behavior, such as reproductive and
      aggressive displays. In the Mozambique tilapia (Oreochromis mossambicus)
      territorial males have higher androgen levels than non-territorials, express
      reproductive behavior and use a urine-borne pheromone to signal their social
      status towards conspecifics. Here we investigated the effects of gonadectomy on
      the circulating levels of androgens and cortisol, and on the expression of
      aggressive and reproductive behavior (nest building, courtship behavior, and
      nuptial coloration). Males were either castrated, urine bladder damaged, or sham
      operated and visually exposed to a group of females during 8 consecutive days and
      subsequently to a male on day 9. The urine bladder damaged treatment was included
      in the experimental design because a full castration procedure in this species
      causes quite often damage to the urine bladder. Gonadectomy lowers dramatically
      the circulating levels of androgens measured at 4 and 8days post-castration and
      abolishes the expression of nest building, courtship behavior and nuptial
      coloration, but has no effect on the expression of aggressive behavior. These
      results confirm the gonads as the main source of androgens in this species and
      show that androgens are necessary for the expression of reproductive behaviors.
      However, the expression of aggressive behavior seems to be decoupled from gonadal
      steroids, namely androgens, suggesting the action of independent central
      mechanisms. 

PMID- 24681191
TI  - Role of thyroid hormones in different aspects of nervous system regeneration in
      vertebrates.
AB  - Spontaneous functional recovery from injury in the adult human nervous system is
      rare and trying to improve recovery remains a clinical challenge. Nervous system
      regeneration is a complicated sequence of events involving cell death or
      survival, cell proliferation, axon extension and remyelination, and finally
      reinnervation and functional recovery. Successful recovery depends on the cell
      specific and time-dependent activation and repression of a wide variety of growth
      factors and guidance molecules. Thyroid hormones (THs), well known for their
      regulatory role in neurodevelopment, have recently emerged as important
      modulators of neuroregeneration. This review focuses on the endogenous changes in
      the proteins regulating TH availability and action in different cell types of the
      adult mammalian nervous system during regeneration as well as the impact of TH
      supplementation on the consecutive steps in this process. It also addresses
      possible differences in TH involvement between different vertebrate classes,
      early or late developmental stages and peripheral or central nervous system. The
      available data show that THs are able to stimulate many signaling pathways
      necessary for successful neurogeneration. They however also suggest that
      supplementation with T4 and/or T3 may have beneficial or detrimental influences
      depending on the dose and more importantly on the specific phase of the
      regeneration process. 

PMID- 24681192
TI  - Crosstalking between the "gut-brain" hormone ghrelin and the circadian system in
      the goldfish. Effects on clock gene expression and food anticipatory activity.
AB  - Ghrelin is a potent orexigenic signal mainly synthesized in the stomach and
      foregut of vertebrates. Recent studies in rodents point out that ghrelin could
      also act as an input for the circadian system and/or as an output of peripheral
      food-entrainable oscillators, being involved in the food anticipatory activity
      (FAA). In this study we pursue the possible interaction of ghrelin with the
      circadian system in a teleost, the goldfish (Carassius auratus). First, we
      analyzed if ghrelin is able to modulate the core clock functioning by regulating
      clock gene expression in fish under a light/dark cycle 12L:12D and fed at 10 am.
      As expected the acute intraperitoneal (IP) injection of goldfish ghrelin (gGRL[1
      19], 44 pmol/g bw) induced the expression of hypothalamic orexin. Moreover,
      ghrelin also induced (~ 2-fold) some Per clock genes in hypothalamus and liver.
      This effect was partially counteracted in liver by the ghrelin antagonist ([D
      Lys(3)]-GHRP-6, 100 pmol/g bw). Second, we investigated if ghrelin is involved in
      daily FAA rhythms. With this aim locomotor activity was studied in response to IP
      injections (5-10 days) of gGRL[1-19] and [D-Lys(3)]-GHRP-6 at the doses above
      indicated. Ghrelin and saline injected fish showed similar 24h activity patterns.
      However, ghrelin antagonist treatment abolished the FAA in schedule fed fish
      under 24h light, suggesting the involvement of the endogenous ghrelin system in
      this pre-feeding activity. Altogether these results suggest that ghrelin could be
      acting as an input for the entrainment of the food-entrainable oscillators in the
      circadian organization of goldfish.

PMID- 24681193
TI  - Effects of intracerebroventricular administered fluoxetine on cardio-ventilatory
      functions in rainbow trout (Oncorhynchus mykiss).
AB  - Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor present in
      the aquatic environment which is known to bioconcentrate in the brains of exposed
      fish. FLX acts as a disruptor of various neuroendocrine functions in the brain,
      but nothing is known about the possible consequence of FLX exposure on the cardio
      ventilatory system in fish. Here we undertook to investigate the central actions
      of FLX on ventilatory and cardiovascular function in unanesthetized rainbow trout
      (Oncorhynchus mykiss). Intracerebroventricular (ICV) injection of FLX (dosed
      between 5 and 25 MUg) resulted in a significantly elevated total ventilation
      (VTOT), with a maximum hyperventilation of +176% (at a dose of 25MUg) compared
      with vehicle injected controls. This increase was due to an increase in
      ventilatory amplitude (VAMP: +126%) with minor effects on ventilatory frequency.
      The highest dose of FLX (25 MUg) produced a significant increase in mean dorsal
      aortic blood pressure (PDA: +20%) without effects on heart rate (fH). In
      comparison, intra-arterial injections of FLX (500-2,500 MUg) had no effect on
      ventilation but the highest doses increased both PDA and fH. The ICV and IA
      cardio-ventilatory effects of FLX were very similar to those previously observed
      following injections of 5-HT, indicating that FLX probably acts via stimulating
      endogenous 5-HT activity through inhibition of 5-HT transporter(s). Our results
      demonstrate for the first time in fish that FLX administered within the brain
      exerts potent stimulatory effects on ventilation and blood pressure increase. The
      doses of FLX given to fish in our study are higher than the brain concentrations
      of FLX in fish that result from acute exposure to FLX through the water.
      Nonetheless, our results indicate possible disrupting action of long term
      exposure to FLX discharged into the environment on central target sites sensitive
      to 5-HT involved in cardio-ventilatory control.

PMID- 24681194
TI  - A new model to study visual attention in zebrafish.
AB  - The major part of cognitive tasks applied to zebrafish has not fully assessed
      their attentional ability, a process by which the nervous system learns,
      organizes sensory input and generates coordinated behaviour. In an attempt to
      maximize the value of zebrafish as an animal model of cognition, we tested the
      possibility to apply a modified version of novel object recognition test named
      virtual object recognition test (VORT) using 2D geometrical shapes (square,
      triangle, circle, cross, etc.) on two iPod 3.5-inch widescreen displays, located
      on two opposite walls of the water tank. Each fish was subjected to a
      familiarization trial (T1), and after different time delays (from 5 min to 96 h)
      to a novel shape recognition trial (T2). A progressive decrease, across time, of
      memory performance, in terms of mean discrimination index and mean exploration
      time, was shown. The predictive validity was tested using cholinergic drugs.
      Nicotine (0.02 mg/kg intraperitoneally, IP) significantly increased, while
      scopolamine (0.025 mg/kg IP) and mecamylamine decreased, mean discrimination
      index. Zebrafish discriminated different movements (vertical, horizontal,
      oblique) and the discrimination index increased significantly when moving poorly
      discriminated shapes were presented, thus increasing visual attention. Taken
      together these findings demonstrate that VORT is a viable, fast and useful model
      to evaluate sustained attention in zebrafish and for predicting the efficacy of
      pharmacotherapies for cognitive disorders.

PMID- 24681195
TI  - Anxiety, hyperactivity and stereotypy in a zebrafish model of fragile X syndrome
      and autism spectrum disorder.
AB  - Fragile X syndrome (FXS) is the most common form of inherited intellectual
      disability and is caused by a loss of function of the fragile X mental
      retardation (fmr1) gene. Animal fmr1-knockout (KO) models are not only of
      interest for the study of FXS, but have also important implications for our
      understanding of autism spectrum disorder (ASD). Here we report the behavioral
      changes in fmr1-knockout zebrafish in an open field with two white and two
      transparent walls. The neophobic responses that in wild-type (WT) zebrafish
      normally occur during the first 5-10 min in an unfamiliar environment (such as
      freezing, hypo-activity and preferences for the bottom and opaque walls of the
      tank), were weakened in fmr1 mutants, suggesting a reduction of novelty-induced
      anxiety. The fmr1-KO zebrafish showed somewhat increased vertical activity beyond
      the 'neophobic phase', but no overall hyperactivity. The mutants demonstrated a
      clear habituation-independent preference for the transparent walls. Whether this
      was attributable to altered spatial information processing or to reduced
      avoidance of open spaces is discussed. Finally, since restrictive repetitive (or
      stereotypical) behaviors are frequently present in FXS and ASD patients, we
      analyzed relative turning angles, directional and preferential turning ratios and
      performed frequency-domain analysis. However, no indications of abnormal movement
      patterning were detected. The possible reasons for the absence of stereotypical
      behaviors are discussed in terms of behavioral endpoint selection and of
      eliciting conditions. Overall, our findings are consistent with those reported in
      fmr1-KO mice and suggest that further analysis of the fmr1-KO zebrafish model has
      potential to deepen our understanding of FXS and ASD. 

PMID- 24681196
TI  - Serotonergic modulation of zebrafish behavior: towards a paradox.
AB  - Due to the fish-specific genome duplication event (~320-350 mya), some genes
      which code for serotonin proteins were duplicated in teleosts; this duplication
      event was preceded by a reorganization of the serotonergic system, with the
      appearance of the raphe nuclei (dependent on the isthmus organizer) and
      prosencephalic nuclei, including the paraventricular and pretectal complexes.
      With the appearance of amniotes, duplicated genes were lost, and the serotonergic
      system was reduced to a more complex raphe system. From a comparative point of
      view, then, the serotonergic system of zebrafish and that of mammals shows many
      important differences. However, many different behavioral functions of serotonin,
      as well as the effects of drugs which affect the serotonergic system, seem to be
      conserved among species. For example, in both zebrafish and rodents acute
      serotonin reuptake inhibitors (SSRIs) seem to increase anxiety-like behavior,
      while chronic SSRIs decrease it; drugs which act at the 5-HT1A receptor seem to
      decrease anxiety-like behavior in both zebrafish and rodents. In this article, we
      will expose this paradox, reviewing the chemical neuroanatomy of the zebrafish
      serotonergic system, followed by an analysis of the role of serotonin in
      zebrafish fear/anxiety, stress, aggression and the effects of psychedelic drugs.

PMID- 24681197
TI  - A dose for the wiser is enough: the alcohol benefits for associative learning in
      zebrafish.
AB  - This study aimed to test seeking behavior caused by alcohol and the drug effects
      on learning in the zebrafish, Danio rerio. Three treatments were conducted:
      acute, chronic and withdrawal, using 0.10%, 0.25%, and 1.00% alcohol and control
      (0.00%) (vol/vol.%). For the drug seeking behavior, we used a place preference
      paradigm (shuttle box tank) before and after alcohol exposure in acute (single
      exposure) and chronic (7 days) treatments. We observed a change in the basal
      preference due to the association with alcohol only for 0.25% and 1.00% doses in
      both acute and chronic offering, indicating an alcohol-seeking behavior after the
      drug exposure. For the learning task, two treatments were tested: chronic alcohol
      exposure (26 days including the learning period) and alcohol withdrawal (15 days
      of alcohol exposure before the learning period). During the learning period, fish
      received light stimulus followed by food in a pre-defined area of the tank for 8
      consecutive days. The low dose group (0.10%) learned the task by the 3rd day both
      in chronic and withdrawal treatments. The higher doses (0.25% and 1.00%) caused a
      learning impairment in the chronic treatment group, while fish from the alcohol
      withdrawal treatment displayed learning on the final testing day. Therefore, we
      suggest that high alcohol doses impair learning and cause drug seeking behavior,
      even after drug exposure cessation, while low doses positively affect learning
      and do not cause seeking behavior. Given our results we propose that the
      zebrafish is a promising model for identifying active compounds, antibodies or
      genes which modulate the alcohol dual effects: learning improvement and
      reinforcing behavior.

PMID- 24681198
TI  - New pathways for bacterial polythioesters.
AB  - Polythioesters (PTE) contain sulfur in the backbone and represent persistent
      biopolymers, which are produced by certain chemical procedures as well as
      biotechnological in vitro and in vivo techniques. Different building blocks can
      be incorporated, resulting in PTE with variable features that could become
      interesting for special purposes. Particularly, the option to produce PTE in
      large-scale and in accordance with the methods of white biotechnology or green
      chemistry is valuable due to economical potentials and public environmental
      consciousness. This review is focused on the synthesis of PTE by the three
      established bacterial production strains Ralstonia eutropha, Escherichia coli and
      Advenella mimigardefordensis. In addition, an overview of the in vitro production
      and degradation of PTE is depicted. 

PMID- 24681199
TI  - A novel automatic suspicious mass regions identification using Havrda & Charvat
      entropy and Otsu's N thresholding.
AB  - Mass detection is a very important process for breast cancer diagnosis and
      computer aided systems. It can be very complex when the mass is small or
      invisible because of dense breast tissue. Therefore, the extraction of suspicious
      mass region can be very challenging. This paper proposes a novel segmentation
      algorithm to identify mass candidate regions in mammograms. The proposed system
      includes three parts: breast region and pectoral muscle segmentation, image
      enhancement and suspicious mass regions identification. The first two parts have
      been examined in previous studies. In this study, we focused on suspicious mass
      regions identification using a combination of Havrda & Charvat entropy method and
      Otsu's N thresholding method. An open access Mammographic Image Analysis Society
      (MIAS) database, which contains 59 masses, was used for the study. The proposed
      system obtained a 93% sensitivity rate for suspicious mass regions identification
      in 56 abnormal and 40 normal images. 

PMID- 24681200
TI  - Typification of virulent and low virulence Babesia bigemina clones by 18S rRNA
      and rap-1c.
AB  - The population structure of original Babesia bigemina isolates and reference
      strains with a defined phenotypic profile was assessed using 18S rRNA and rap-1c
      genes. Two reference strains, BbiS2P-c (virulent) and BbiS1A-c (low virulence),
      were biologically cloned in vitro. The virulence profile of the strains and
      clones was assessed in vivo. One fully virulent and one low-virulence clone were
      mixed in identical proportions to evaluate their growth efficiency in vitro. Each
      clone was differentiated by two microsatellites and the gene gp45. The 18S rRNA
      and rap-1c genes sequences from B. bigemina biological clones and their parental
      strains, multiplied exclusively in vivo or in vitro, were compared with strain JG
      29. The virulence of clones derived from the BbiS2P-c strain was variable.
      Virulent clone Bbi9P1 grew more efficiently in vitro than did the low-virulence
      clone Bbi2A1. The haplotypes generated by the nucleotide polymorphism, localized
      in the V4 region of the 18S rRNA, allowed the identification of three genotypes.
      The rap-1c haplotypes allowed defining four genotypes. Parental and original
      strains were defined by multiple haplotypes identified in both genes. The rap-1c
      gene, analyzed by high-resolution melting (HRM), allowed discrimination between
      two genotypes according to their phenotype, and both were different from JG-29.
      B. bigemina biological clones made it possible to define the population structure
      of isolates and strains. The polymorphic regions of the 18S rRNA and rap-1c genes
      allowed the identification of different subpopulations within original B.
      bigemina isolates by the definition of several haplotypes and the differentiation
      of fully virulent from low virulence clones. 

PMID- 24681201
TI  - Our stolen figures: the interface of sexual differentiation, endocrine
      disruptors, maternal programming, and energy balance.
AB  - This article is part of a Special Issue "Energy Balance". The prevalence of adult
      obesity has risen markedly in the last quarter of the 20th century and has not
      been reversed in this century. Less well known is the fact that obesity
      prevalence has risen in domestic, laboratory, and feral animals, suggesting that
      all of these species have been exposed to obesogenic factors present in the
      environment. This review emphasizes interactions among three biological processes
      known to influence energy balance: Sexual differentiation, endocrine disruption,
      and maternal programming. Sexual dimorphisms include differences between males
      and females in body weight, adiposity, adipose tissue distribution, ingestive
      behavior, and the underlying neural circuits. These sexual dimorphisms are
      controlled by sex chromosomes, hormones that masculinize or feminize adult body
      weight during perinatal development, and hormones that act during later periods
      of development, such as puberty. Endocrine disruptors are natural and synthetic
      molecules that attenuate or block normal hormonal action during these same
      developmental periods. A growing body of research documents effects of endocrine
      disruptors on the differentiation of adipocytes and the central nervous system
      circuits that control food intake, energy expenditure, and adipose tissue
      storage. In parallel, interest has grown in epigenetic influences, including
      maternal programming, the process by which the mother's experience has permanent
      effects on energy-balancing traits in the offspring. This review highlights the
      points at which maternal programming, sexual differentiation, and endocrine
      disruption might dovetail to influence global changes in energy balancing traits.

PMID- 24681202
TI  - Gene-disease association with literature based enrichment.
AB  - MOTIVATION: Gene set enrichment analysis (GSEA) annotates gene microarray data
      with functional information from the biomedical literature to improve gene
      disease association prediction. We hypothesize that supplementing GSEA with
      comprehensive gene function catalogs built automatically using information
      extracted from the scientific literature will significantly enhance GSEA
      prediction quality. METHODS: Gold standard gene sets for breast cancer (BrCa) and
      colorectal cancer (CRC) were derived from the literature. Two gene function
      catalogs (CMeSH and CUMLS) were automatically generated. 1. By using Entrez Gene
      to associate all recorded human genes with PubMed article IDs. 2. Using the genes
      mentioned in each PubMed article and associating each with the article's MeSH
      terms (in CMeSH) and extracted UMLS concepts (in CUMLS). Microarray data from the
      Gene Expression Omnibus for BrCa and CRC was then annotated using CMeSH and CUMLS
      and for comparison, also with several pre-existing catalogs (C2, C4 and C5 from
      the Molecular Signatures Database). Ranking was done using, a standard GSEA
      implementation (GSEA-p). Gene function predictions for enriched array data were
      evaluated against the gold standard by measuring area under the receiver
      operating characteristic curve (AUC). RESULTS: Comparison of ranking using the
      literature enrichment catalogs, the pre-existing catalogs as well as five
      randomly generated catalogs show the literature derived enrichment catalogs are
      more effective. The AUC for BrCa using the unenriched gene expression dataset was
      0.43, increasing to 0.89 after gene set enrichment with CUMLS. The AUC for CRC
      using the unenriched gene expression dataset was 0.54, increasing to 0.9 after
      enrichment with CMeSH. C2 increased AUC (BrCa 0.76, CRC 0.71) but C4 and C5
      performed poorly (between 0.35 and 0.5). The randomly generated catalogs also
      performed poorly, equivalent to random guessing. DISCUSSION: Gene set enrichment
      significantly improved prediction of gene-disease association. Selection of
      enrichment catalog had a substantial effect on prediction accuracy. The
      literature based catalogs performed better than the MSigDB catalogs, possibly
      because they are more recent. Catalogs generated automatically from the
      literature can be kept up to date. CONCLUSION: Prediction of gene-disease
      association is a fundamental task in biomedical research. GSEA provides a
      promising method when using literature-based enrichment catalogs. AVAILABILITY:
      The literature based catalogs generated and used in this study are available from
      http://www2.chi.unsw.edu.au/literature-enrichment.

PMID- 24681203
TI  - ORC1/CDC6 and MCM7 distinct associate with chromatin through Trypanosoma cruzi
      life cycle.
AB  - Trypanosoma cruzi alternates between replicative and non-replicative stages. We
      analyzed the expression of components of the pre-replication machinery
      TcORC1/CDC6 and TcMCM7 and their interaction with DNA in all T. cruzi stages.
      TcORC1/CDC6 remains in the nuclear space during all stages of the life cycle and
      interacts with DNA in the replicative stages; however, it does not bind to DNA in
      the non-replicative forms. Moreover, TcMCM7 is not present in the non-replicative
      stages. These data suggest that the lacking of DNA replication during the T.
      cruzi life cycle may be a consequence of the blocking of TcORC1/CDC6-DNA
      interaction and of the down regulation of the TcMCM7 expression. 

PMID- 24681204
TI  - Isolation and cultivation of metabolically competent alveolar epithelial cells
      from A/J mice.
AB  - The A/J mouse strain is used in lung cancer studies. To enable mechanistic
      investigations the isolation and cultivation of alveolar epithelial cells (AECs)
      is desirable. Based on four different protocols dispase digestion of lung tissue
      was best and yielded 9.3 +/- 1.5 * 10(6) AECs. Of these 61 +/- 13% and 43 +/- 5%
      were positive for AP and NBT staining, respectively. Purification by
      discontinuous Percoll gradient centrifugation did not change this ratio; however,
      reduced the total cell yield to 4.4 +/- 1.1 * 10(6) AECs. Flow cytometry of
      lectin bound AECs determined 91 +/- 7% and 87 +/- 5% as positive for Helix
      pomatia and Maclura pomifera to evidence type II pneumocytes. On day 3 in culture
      the ethoxyresorufin-O-demethylase activity was 251 +/- 80 pmol/4 h * 1.5 * 10(6)
      and the production of androstenedione proceed at 243.5 +/- 344.4 pmol/24 h * 1.5
      * 10(6) AECs. However, 6-alpha, 6-beta and 16-beta-hydroxytestosterone were
      produced about 20-fold less as compared to androstenedione and the production of
      metabolites depended on the culture media supplemented with 2% mouse serum or 10%
      FCS. Finally, by RT-PCR expression of CYP genes was confirmed in lung tissue and
      AECs; a link between testosterone metabolism and CYP2A12, 3A16 and 2B9/10
      expression was established. Taken collectively, AECs can be successfully isolated
      and cultured for six days while retaining metabolic competence.

PMID- 24681205
TI  - Vandetanib-induced phototoxicity in human keratinocytes NCTC-2544.
AB  - The phototoxicity of the new anticancer drug vandetanib was evaluated using human
      keratinocyte cell line, NCTC-2544. This study was started since many clinical
      cases of vandetanib photosensitizing reactions were recently reported in
      literature. Vandetanib induces a clear drop in human keratinocytes viability
      after cell irradiation in concentration and UV-A dose dependent mode. Since
      vandetanib can photolyze with the formation of two main photoproducts after UV-A
      exposure, the contribution of these new species was also evaluated. These two
      photoproducts did not have a main role in the phototoxicity of their parent drug.
      In our opinion, the main hypothesis for the vandetanib phototoxic potential is
      the formation of a very reactive specie, such as an aryl radical, which can react
      promptly with different targets inside the cells. In fact, a massive DNA
      photodamage was detected both in the in vitro DNA photocleavage experiments, and
      in cells. Moreover, vandetanib was able to photoinduce lipid peroxidation and
      protein oxidations. Vandetanib photoinduced cell death by apoptosis with the
      involvement of mitochondria and lysosomes. 

PMID- 24681207
TI  - Comparison of Enterococcus quantitative polymerase chain reaction analysis
      results from Midwest U.S. river samples using EPA Method 1611 and Method 1609 PCR
      reagents.
AB  - Enterococci target sequence density estimates from analyses of diluted river
      water DNA extracts by EPA Methods 1611 and 1609 and estimates with lower
      detection limits from undiluted DNA extracts by Method 1609 were
      indistinguishable. These methods should be equally suitable for comparison with
      U.S. EPA 2012 Recreational Water Quality Criteria values. 

PMID- 24681206
TI  - Expression analysis of Dact1 in mice using a LacZ reporter.
AB  - The Wnt signaling pathway is essential for cell fate decisions during embryonic
      development as well as for homeostasis after birth. Dapper antagonist of catenin
      1 (Dact1) plays an important role during embryogenesis by regulating Wnt
      signaling pathways. Consequently, targeted disruption of the Dact1 gene in mice
      leads to perinatal lethality due to severe developmental defects involving the
      central nervous system, genitourinary system and distal digestive tract. However,
      the expression and potential function of Dact1 in other tissues during
      development and postnatal life have not been well studied. Here, we have
      generated reporter mice in which LacZ expression is driven by the Dact1 gene
      promoter and characterized Dact1-LacZ expression in embryos and adult tissues.
      Our data show that while Dact1-LacZ is expressed in multiple mesoderm- and
      neuroectoderm-derived tissues during development, high expression of Dact1-LacZ
      is restricted to a small subset of adult tissues, including the brain, eye,
      heart, and some reproductive organs. These results will serve as a basis for
      future investigation of Dact1 function in Wnt-mediated organogenesis and tissue
      homeostasis.

PMID- 24681208
TI  - A unique method for the isolation of nasal olfactory stem cells in living rats.
AB  - Stem cells are attractive tools to develop new therapeutic strategies for a
      variety of disorders. While ethical and technical issues, associated with
      embryonic, fetal and neural stem cells, limit the translation to clinical
      applications, the nasal stem cells identified in the human olfactory mucosa stand
      as a promising candidate for stem cell-based therapies. Located in the back of
      the nose, this multipotent stem cell type is readily accessible in humans, a
      feature that makes these cells highly suitable for the development of autologous
      cell-based therapies. However, preclinical studies based on autologous
      transplantation of rodent olfactory stem cells are impeded because of the narrow
      opening of the nasal cavity. In this study, we report the development of a unique
      method permitting to quickly and safely biopsy olfactory mucosa in rats. Using
      this newly developed technique, rat stem cells expressing the stem cell marker
      Nestin were successfully isolated without requiring the sacrifice of the donor
      animal. As an evidence of the self-renewal capacity of the isolated cells,
      several millions of rat cells were amplified from a single biopsy within four
      weeks. Using an olfactory discrimination test, we additionally showed that this
      novel biopsy method does not affect the sense of smell and the learning and
      memory abilities of the operated animals. This study describes for the first time
      a methodology allowing the derivation of rat nasal cells in a way that is
      suitable for studying the effects of autologous transplantation of any cell type
      present in the olfactory mucosa in a wide variety of rat models. 

PMID- 24681209
TI  - Characterization and structural analysis of human selenium-dependent glutathione
      peroxidase 4 mutant expressed in Escherichia coli.
AB  - Glutathione peroxidase 4 (GPx4) is a monomeric selenium-dependent glutathione
      peroxidase highly expressed in mammalian cells, which can reduce phospholipid
      hydroperoxides. However, it has been difficult to express recombinant mammalian
      GPx4 in Escherichia coli because of the differences in the selenocysteine (Sec)
      incorporation machinery between eukaryotes and prokaryotes. In this study, an E.
      coli BL21(DE3)cys auxotrophic strain was used to express GPx4 mutants. We found
      that untargeted substitution of Cys-2, Cys-37, Cys-75, Cys-107, and Cys-148 with
      Sec led to loss of activity, suggesting that mutation of any of these Cys
      residues in GPx4 could result in a structural change. Additionally, we found that
      the catalytic activity of GPx4 mutants increased as the number of noncatalytic
      Sec residues decreased, indicating that the negative effects could be mitigated
      by replacing these Cys residues with Ser residues. A GPx4 mutant with all Cys
      residues converted to Ser exhibited a "Ping-Pong" mechanism and structure similar
      to that of native GPx4, indicating that it could act as a substitute for GPx4,
      when heterologously expressing the protein in E. coli. This research provides an
      important foundation for biosynthesis of selenium-dependent GPx4 mutants in E.
      coli. 

PMID- 24681210
TI  - Special issue on exercise immunology: current perspectives on aging, health and
      extreme performance.
AB  - The aim of this special issue is to highlight outstanding exemplars of empirical
      research and review papers that reflect the breadth of current developments in
      exercise immunology. The contributions to this issue are categorized according to
      four major themes: (1) exercise and immune-aging; (2) the effects of acute
      exercise on cellular shifts and gene expression; (3) the effects of exercise on
      immune regulation during stress and disease; and (4) extreme performance and the
      impact of dietary counter measures on immunity. We discuss the papers appearing
      in this issue, in accordance with these major themes, and summarize their
      important contributions to this exciting and expanding field. 

PMID- 24681211
TI  - Rosiglitazone stimulates peroxisome proliferator-activated receptor gamma
      expression and directly affects in vitro steroidogenesis in porcine ovarian
      follicles.
AB  - Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARgamma)
      synthetic activator from the group of thiazolidinediones often used in the
      treatment of chronic diseases such as type 2 diabetes and other forms of insulin
      resistance. The present in vitro study assessed the direct effects of
      rosiglitazone at 25 and 50 MUM doses on PPARgamma gene expression, steroid
      secretion (progesterone [P4], androstenedione [A4], testosterone [T], and
      estradiol), and protein expression of PPARgamma, 3betaHSD, CYP17, 17betaHSD,
      CYP19 by porcine ovarian follicles from prepubertal and cycling animals. We
      analyzed also steroid enzymatic activity by conversion of pregnen-3beta-ol-20-one
      to P4, P4 to A4, and A4 to T. Our results indicated that rosiglitazone increased
      significantly PPARgamma expression, P4 secretion, 3betaHSD activity, and protein
      expression. Rosiglitazone decreased A4 and T secretion by reducing the expression
      and activity of CYP17 and 17betaHSD and did not change estradiol secretion and
      CYP19. Similarly results was observed both in prepubertal and cycling pigs. Our
      results indicate that these direct effects of rosiglitazone on ovarian
      steroidogenesis provide a framework for testing several potential new mechanisms
      of PPAR-gamma actions on porcine ovarian function. 

PMID- 24681212
TI  - Fecal endocrine monitoring of reproduction in female snow leopards (Uncia uncia).
AB  - Although the snow leopard (Uncia uncia) is a common endangered felid species in
      zoos, little is known about the complex endocrine interactions controlling
      ovarian function and conception in this species. The goal of this work was to
      characterize ovarian activity throughout the estrous cycle, nonpregnant luteal
      phase (pseudopregnancy), and gestation in female snow leopards. This goal was
      accomplished using an enzyme immunoassay to measure fecal concentrations of
      estrogen metabolites (E) and progesterone metabolites (P). Fecal samples were
      collected from 12 female snow leopards (ages 18 months to 18 years) during one to
      three breeding seasons. In each breeding season, the majority of females (78%,
      88%, and 100%, respectively) began to exhibit ovarian activity in December or
      January. The estrous cycle, defined by the first day of estrus (E >= 2 * basal
      concentration) to the first day of the subsequent estrus, was 12.7 +/- 0.6 days
      (n = 145 cycles). Estrus lasted 4.3 +/- 0.4 days with mean concentrations of
      fecal E during the follicular phase (1661 +/- 139 ng/g feces) increasing 3.2-fold
      above basal concentrations (515 +/- 32 ng/g feces). No spontaneous ovulations
      were observed in any of the cycling females. Nonpregnant luteal phases were
      observed in eight females that bred but did not become pregnant. The length of
      the nonpregnant luteal phase ranged from 11 to 72 days (45.7 +/- 5.7 days; n =
      10) with mean concentrations of fecal P during the luteal phase (12.46 +/- 1.7
      MUg/g feces) increasing 6.2-fold above basal concentrations of P (2.01 +/- 0.2
      MUg/g feces). Three of the females in the study became pregnant and gave birth
      after a gestation of 93 (n = 2) and 95 (n = 1) days. Fecal P concentrations
      during pregnancy increased to 11.64 +/- 1.3 MUg/g feces, or 5.8-fold above basal
      concentrations. The results of this study provide a comprehensive
      characterization of reproductive endocrinology in snow leopards, and confirm that
      fecal hormone monitoring is an effective way to monitor female snow leopards
      throughout the breeding season.

PMID- 24681213
TI  - Use of mesenchymal stem cells or autologous conditioned serum to modulate the
      inflammatory response to spermatozoa in mares.
AB  - Current treatments for Persistent mating-induced endometritis such as uterine
      lavage and oxytocin therapy focus on aiding the uterus in removal of inflammatory
      products, but these treatments do not modulate the inciting inflammatory
      response. Biological treatments, such as autologous conditioned serum (ACS) and
      mesenchymal stem cells (MSCs), have been used in human and veterinary medicine
      for immunomodulation for over 10 years. The objectives of this project were to
      evaluate the ability of ACS or MSCs to modulate the inflammatory response to
      spermatozoa after breeding. Two experiments were performed with six normal mares
      in each study to evaluate the effects of intrauterine administration of ACS,
      dexamethasone, or a placebo (experiment 1), or allogeneic MSCs or a placebo
      (experiment 2) on the inflammatory response to spermatozoa using clinical and
      biochemical endpoints. Treatment with ACS and MSCs significantly (P < 0.05)
      reduced the number of neutrophils in the uterine lumen 6 hours after the sperm
      challenge. An increase (P < 0.05) in the anti-inflammatory cytokine IL-1Ra was
      observed after treatment with MSCs before exposure to spermatozoa. There was no
      difference in IL-1Ra concentration in mares treated with ACS, dexamethasone, or a
      placebo. Mesenchymal stem cells and ACS were able to modulate the immune response
      to spermatozoa in normal mares. The effect may be due to an increase in IL-1Ra in
      MSCs-treated mares, but other bioactive molecules may be responsible for the
      decrease in neutrophils in ACS-treated mares. Autologous conditioned serum and
      bone-derived culture expanded MSCs were able to modulate the uterine inflammatory
      response to spermatozoa in normal mares. Treatment with allogeneic stem cells may
      be beneficial if a similar modulation in inflammatory cytokines occurs in mares
      affected by persistent mating-induced endometritis. 

PMID- 24681214
TI  - ROCK inhibitor Y-27632 prevents porcine oocyte maturation.
AB  - The inhibitor Y-27632 is a specific selective inhibitor of Rho-associated protein
      kinases (ROCKs), which are downstream effectors of Rho guanosine triphosphatease
      (GTPases) and regulate Rho-associated cellular functions, including actin
      cytoskeletal organization. Little is known regarding the effects of Y-27632 on
      mammalian oocyte maturation. In the present study, we investigated the effects of
      Y-27632 on porcine oocyte meiosis and possible regulatory mechanisms of ROCK
      during porcine oocyte maturation. We found that ROCK accumulated not only at
      spindles, but also at the cortex in porcine oocytes. Y-27632 treatment reduced
      ROCK expression, and inhibited porcine oocyte meiotic maturation, which might be
      because of the impairment of actin expression and actin-related spindle
      positioning. Y-27632 treatment also disrupted the formation of actin cap and
      cortical granule-free domain, which further confirmed a spindle positioning
      failure. Thus, Y-27632 has significant effects on the meiotic competence of
      mammalian oocytes by reducing ROCK expression, and the regulation is related to
      its effects on actin-mediated spindle positioning. 

PMID- 24681215
TI  - Chronic enhancement of brain oxytocin levels causes enduring anti-aggressive and
      pro-social explorative behavioral effects in male rats.
AB  - Oxytocin (OXT) has been implicated in the regulation of social behaviors,
      including intermale offensive aggression. Recently, we showed that acute
      enhancement of brain OXT levels markedly suppressed offensive aggression and
      increased social exploration in resident rats confronted with an intruder in
      their home territory. Moreover, a different responsivity to the exogenous
      OXTergic manipulation was observed among individuals based on their baseline
      aggression. In this study we aimed at evaluating the behavioral response to
      chronically enhancing or attenuating central OXT levels, and at scrutinizing
      whether the trait-aggression moderates the treatment-induced behavioral changes.
      To this end, resident male wild-type Groningen rats were continuously (via
      osmotic minipumps) intracerebroventricularly infused with synthetic OXT or a
      selective OXT receptor (OXTR) antagonist for 7days. Changes in behavior were
      assessed performing a resident-intruder test before and at the end of the
      treatment period, as well as after 7days of withdrawal. Chronic infusion of OXT
      was found to selectively suppress aggression and enhance social exploration.
      Chronic blockage of OXTRs instead increased introductory aggressive behavior
      (i.e. lateral threat), yet without affecting the total duration of the
      aggression. The magnitude of the anti-aggressive changes correlated positively
      with the level of baseline aggression. Interestingly, OXT-induced behavioral
      changes persisted 7days after cessation of the treatment. In conclusion, these
      findings provide further evidence that enhanced functional activity of the
      central OXTergic system decreases social offensive aggression while it increases
      social explorative behavior. The data also indicate that chronically enhancing
      brain OXT levels may cause enduring anti-aggressive and pro-social explorative
      behavioral effects. 

PMID- 24681217
TI  - Food hoarding, but not food intake, is attenuated by acute diazepam treatment in
      female Mongolian gerbils (Meriones unguiculatus).
AB  - This article is part of a Special Issue "Energy Balance". Effects of gamma
      aminobutyric acid (GABA) on food hoarding are unknown in rodents, and the effects
      of energy balance and GABA have not been evaluated in females. To evaluate the
      role of food deprivation and GABA on food hoarding, female Mongolian gerbils were
      given i.p. injection of diazepam (1mg/kg and 3mg/kg, respectively), a GABAA
      receptor agonist. Among food-deprived females, there was a bimodal pattern in the
      frequency of gerbils with different levels of food hoarding. High food hoarding
      (HFH) and low food hoarding (LFH) gerbils were analyzed. Diazepam blocked food
      deprivation-induced food hoarding in HFH gerbils, but not in LFH gerbils. This
      blockade was associated with increased cellular activation in selected brain
      areas, such as the nucleus accumbens (NAcc), caudate putamen (CP) and ventral
      tegmental area (VTA), which suggested that direct activation of GABA in the brain
      reward circuitry decreased food hoarding in HFH females. Moreover, diazepam
      increased Fos expression in field CA2 and CA3 of the hippocampus, but had no
      significant effect on Fos expression in field CA1 and dentate gyrus (DG) of the
      hippocampus, indicating that the hippocampus has area-specific effects on food
      hoarding in HFH gerbils. Diazepam did not alter food intake in both HFH and LFH
      gerbils. In addition, serum corticosterone concentrations were higher in the HFH
      than in the LFH ones. Together, these data indicated that food deprivation
      increased food hoarding in female gerbils, diazepam reduced food deprivation
      induced food hoarding in HFH gerbils, and that GABA might influence food hoarding
      via classical reward circuitry via the mesolimbic dopamine system and specific
      hippocampal areas. 

PMID- 24681218
TI  - Differential T-cell responses of semi-immune and susceptible malaria subjects to
      in silico predicted and synthetic peptides of Plasmodium falciparum.
AB  - Malaria remains a public health hazard in tropical countries as a consequence of
      the rise and spread of drug and insecticide resistances; hence the need for a
      vaccine with widespread application. Protective immunity to malaria is known to
      be mediated by both antibody and cellular immune responses, though
      characterization of the latter has been less extensive. The aim of the present
      investigation was to identify novel T-cell epitopes that may contribute to
      naturally acquired immune responses against malaria. Using the Microsoft
      software, EpitomeTM T-cell peptide epitopes on 19 Plasmodium falciparum proteins
      in the Plasmodium Database (www.plasmodb.org.PlasmoDB 9.0) were predicted in
      silico. The peptides were synthesized and used to stimulate peripheral blood
      mononuclear cells (PBMCs) in 14 semi-immune and 21 malaria susceptible subjects
      for interferon-gamma (IFN-gamma) production ex-vivo. The level of IFN-gamma
      production, a marker of T-cell responses, was measured by ELISPOT assay in semi
      immune subjects (SIS) and frequently sick subjects (FSS) from an endemic zone
      with perennial malaria transmission. Of the 19 proteins studied, 17 yielded 27
      pools (189 peptides), which were reactive with the subjects' PBMCs when tested
      for IFN-gamma production, taking a stimulation index (SI) of >=2 as a cutoff
      point for a positive response. There were 10 reactive peptide pools (constituting
      eight protein loci) with an SI of 10 or greater. Of the 19 proteins studied, two
      were known vaccine candidates (MSP-8 and SSP2/TRAP), which reacted both with SIS
      and FSS. Similarly the hypothetical proteins (PFF1030w, PFE0795c, PFD0880w,
      PFC0065c and PF10_0052) also reacted strongly with both SIS and FSS making them
      attractive for further characterization as mediators of protective immunity
      and/or pathogenesis.

PMID- 24681219
TI  - Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the Ouest
      and Sud-Est departments of Haiti.
AB  - Malaria remains a significant public health issue in Haiti, with chloroquine (CQ)
      used almost exclusively for the treatment of uncomplicated infections. Recently,
      single dose primaquine (PQ) was added to the Haitian national malaria treatment
      policy, despite a lack of information on the prevalence of glucose-6-phosphate
      dehydrogenase (G6PD) deficiency within the population. G6PD deficient individuals
      who take PQ are at risk of developing drug induced hemolysis (DIH). In this first
      study to examine G6PD deficiency rates in Haiti, 22.8% (range 14.9%-24.7%) of
      participants were found to be G6PD deficient (class I, II, or III) with 2.0%
      (16/800) of participants having severe deficiency (class I and II). Differences
      in deficiency were observed by gender, with males having a much higher prevalence
      of severe deficiency (4.3% vs. 0.4%) compared to females. Male participants were
      1.6 times more likely to be classified as deficient and 10.6 times more likely to
      be classified as severely deficient compared to females, as expected. Finally,
      10.6% (85/800) of the participants were considered to be at risk for DIH. Males
      also had much higher rates than females (19.3% vs. 4.6%) with 4.9 times greater
      likelihood (p value 0.000) of having an activity level that could lead to DIH.
      These findings provide useful information to policymakers and clinicians who are
      responsible for the implementation of PQ to control and manage malaria in Haiti. 

PMID- 24681216
TI  - On the value of seasonal mammals for identifying mechanisms underlying the
      control of food intake and body weight.
AB  - This article is part of a Special Issue "Energy Balance". Seasonal cycles of
      adiposity and body weight reflecting changes in both food intake and energy
      expenditure are the norm in mammals that have evolved in temperate and polar
      habitats. Innate circannual rhythmicity and direct responses to the annual change
      in photoperiod combine to ensure that behavior and energy metabolism are
      regulated in anticipation of altered energetic demands such as the energetically
      costly processes of hibernation, migration, and lactation. In the last decade,
      major progress has been made into identifying the central mechanisms that
      underlie these profound long-term changes in behavior and physiology.
      Surprisingly they are distinct from the peptidergic and aminergic systems in the
      hypothalamus that have been identified in studies of the laboratory mouse and rat
      and implicated in timing meal intervals and in short-term responses to caloric
      restriction. Comparative studies across rodents, ungulates and birds reveal that
      tanycytes embedded in the ependymal layer of the third ventricle play a critical
      role in seasonal changes because they regulate the local availability of thyroid
      hormone. Understanding how this altered hormonal environment might regulate
      neurogenesis and plasticity in the hypothalamus should provide new insight into
      development of strategies to manage appetite and body weight. 

PMID- 24681220
TI  - In-vitro anti-inflammatory and mosquito larvicidal efficacy of nickel
      nanoparticles phytofabricated from aqueous leaf extracts of Aegle marmelos
      Correa.
AB  - In recent years there is a tremendous growth in the interdisciplinary world of
      nanotechnology across the globe and emergence of its potential applications
      remains as a big revolution to the industry. Fusion of green nanotechnology and
      medicine represents one of the major breakthroughs of modern science with the aim
      of developing nanomaterials for diagnosis, treatment, prevention of various
      diseases and overall improving health for the beneficial of mankind. In the
      present study phytofabrication of nickel nanoparticles (nickel NPs) was carried
      out by using indigenous Aegle marmelos Correa aqueous leaf extracts as a
      reducing, stabilizing and capping agents. Nickel NPs were characterized by UV
      spectroscopy, FTIR, XRD, SEM, AFM and TGA studies. Phytosynthesis of nickel NPs
      was monitored both at room temperature (25 degrees C) and at 60 degrees C for 5h.
      The green synthesis of triangular shape nickel NPs phytofabricated from A.
      marmelos Correa aqueous leaf extracts having face centered cubic structure
      showing an average particle size of 80-100nm which is in consistent with the
      particle size calculated by XRD Scherer equation. We further explored and
      compared nickel NPs of A. marmelos Correa with crude leaf extracts of A. marmelos
      Correa for its in-vitro anti-inflammatory and mosquito larvicidal efficacy
      against three blood feeding parasites. The results obtained clearly gives an idea
      that nickel NPs of A. marmelos Correa (NiNPs of AmC) possess an enhanced anti
      inflammatory and larvicidal activity when compared to crude leaf extracts of A.
      marmelos Correa. 

PMID- 24681221
TI  - Domestic dog health worsens with socio-economic deprivation of their home
      communities.
AB  - Dogs play an important role in infectious disease transmission as reservoir hosts
      of many zoonotic and wildlife pathogens. Nevertheless, unlike wildlife species
      involved in the life cycle of pathogens, whose health status might be a direct
      reflection of their fitness and competitive abilities, dog health condition could
      be sensitive to socio-economic factors impacting the well-being of their owners.
      Here, we compare several dog health indicators in three rural communities of
      Panama with different degrees of socio-economic deprivation. From a total of 78
      individuals, we collected blood and fecal samples, and assessed their body
      condition. With the blood samples, we performed routine hematologic evaluation
      (complete blood counts) and measured cytokine levels (Interferon-gamma and
      Interleukin-10) through enzyme-linked immunosorbent assays. With the fecal
      samples we diagnosed helminthiases. Dogs were also serologically tested for
      exposure to Trypanosoma cruzi and canine distemper virus, and molecular tests
      were done to assess T. cruzi infection status. We found significant differences
      between dog health measurements, pathogen prevalence, parasite richness, and
      economic status of the human communities where the dogs lived. We found dogs that
      were less healthy, more likely to be infected with zoonotic pathogens, and more
      likely to be seropositive to canine distemper virus in the communities with lower
      economic status. This study concludes that isolated communities of lower economic
      status in Panama may have less healthy dogs that could become major reservoirs in
      the transmission of diseases to humans and sympatric wildlife. 

PMID- 24681222
TI  - Laboratory and field evaluation of rodent bait treated with fipronil for feed
      through and systemic control of Phlebotomus papatasi.
AB  - The sand fly Phlebotomus papatasi is the main vector of Leishmania major,
      etiologic agent of zoonotic cutaneous leishmaniasis (ZCL), which is endemic in
      North Africa, the Middle East, and Asia. In North Africa, Meriones shawi is one
      of the two main reservoir hosts of L. major. P. papatasi populations are
      maintained in borrowing rodents such as M. shawi. Three fipronil-treated rodent
      baits were evaluated for systemic and feed through insecticidal activity against
      P. papatasi feeding on M. shawi. Through blood feeding bioassays, mortality rates
      of females P. papatasi increased with the concentration of fipronil in the rodent
      bait varying from 0.001% to 0.005%. In the laboratory, more than 90.0% of P.
      papatasi were killed within 48h after blood feeding on the desert's jirds, M.
      shawi, treated up to 29 days prior with a single application of fipronil at a
      concentration of 0.001%, 0.0025% and 0.005%. Through larval bioassays, mortality
      rates of larvae that have fed on faeces of treated bait for M. shawi increase
      with the concentrations of fipronil. Faeces of orally-treated Meriones were
      significantly toxic to larvae for 5 weeks with a concentration of 0.005%. In the
      field, application of treated bait resulted in 80.0% reduction in the populations
      of P. papatasi up to 6 weeks after a single application of fipronil at a
      concentration of 0.005%. This is the first study to demonstrate field efficacy of
      fipronil-treated rodent baits for P. papatasi control and the first study to
      evaluate this approach in M. shawi, a principal ZCL reservoir host. These results
      suggest that fipronil-treated rodent baits can be used to effectively reduce the
      populations of P. papatasi associated with M. shawi in ZCL endemic areas. 

PMID- 24681223
TI  - Description and analysis of the poultry trading network in the Lake Alaotra
      region, Madagascar: implications for the surveillance and control of Newcastle
      disease.
AB  - Madagascar's 36.5-million-head poultry industry holds a foremost place in its
      economy and the livelihood of its people. Unfortunately, regular Newcastle
      disease outbreaks associated with high mortality causes high losses for
      smallholders and threatens their livelihood. Therefore, Madagascar is seeking
      concrete, achievable and sustainable methods for the surveillance and the control
      of Newcastle disease. In this paper, we present and analyze the results of a
      field study conducted in Madagascar between December 2009 and December 2010. The
      study area was the Lac Alaotra region, a landlocked area in the north-eastern
      part of the country's center. Poultry trading is suspected of playing a major
      role in the spread of avian diseases, especially in developing countries
      characterized by many live-bird markets and middlemen. Therefore, the goals of
      our study were to: (i) describe and analyze smallholders' poultry trading network
      in the Lake Alaotra region using social network analysis; (ii) assess the role of
      the network in the spread of Newcastle disease; and (iii) propose the
      implementation of a targeted disease surveillance based on the characteristics of
      the poultry trading network. We focused our field study on the harvesting of two
      data sets. The first is a complete description of the poultry trading network in
      the landlocked area of Lac Alaotra, including a description of the poultry
      movements between groups of villages. The second set of data measures the
      occurrence of outbreaks in the same area by combining a participatory approach
      with an event-based surveillance method. These data were used to determine the
      attributes of the network, and to statistically assess the association between
      the position of nodes and the occurrence of outbreaks. By using social network
      analysis techniques combined with a classification method and a logistic model,
      we finally identified 3 nodes (set of villages), of the 387 in the initial
      network, to focus on for surveillance and control in the Lac Alaotra area. This
      result is of primary importance in the ongoing efforts to effectively improve the
      wellbeing of people in the region. 

PMID- 24681224
TI  - Bioactive compound loaded stable silver nanoparticle synthesis from microwave
      irradiated aqueous extracellular leaf extracts of Naringi crenulata and its wound
      healing activity in experimental rat model.
AB  - An efficient and eco-friendly protocol for the synthesis of bioactive silver
      nanoparticles was developed using Naringi crenulata leaf extracts via microwave
      irradiation method. Silver nanoparticles were synthesized by treating N.
      crenulata leaf extracts with 1mM of aqueous silver nitrate solution. An effective
      bioactive compound such as alkaloids, phenols, saponins and quinines present in
      the N. crenulata reduces the Ag(+) into Ag(0). The synthesized silver
      nanoparticles were monitored by UV-vis spectrophotometer and further
      characterized by X-ray diffraction (XRD), Fourier Transform Infra Red (FTIR),
      Energy-dispersive X-ray spectroscopy (EDX) and field emission scanning electron
      microscopy (FESEM). UV-vis spectroscopy showed maximum absorbance at 390nm due to
      surface plasmon resonance of AgNPs. From FESEM results, an average crystal size
      of the synthesized nanoparticle was 72-98nm. FT-IR results showed sharp
      absorption peaks and they were assigned to phosphine, alkyl halides and sulfonate
      groups. Silver nanoparticles synthesized were generally found to be spherical and
      cubic shape. Topical application of ointment prepared from silver nanoparticles
      of N. crenulata were formulated and evaluated in vivo using the excision wound
      healing model on Wistar albino rats. The measurement of the wound areas was
      performed on 3rd, 6th, 9th, 12th and 15th days and the percentage of wound
      closures was calculated accordingly. By the 15th day, the ointment base
      containing 5% (w/w) of silver nanoparticles showed 100% wound healing activity
      compared with that of the reference as well as control bases. The results
      strongly suggested that the batch C ointment containing silver nanaoparticles
      synthesized from the leaf extracts of N. crenulata was found to be very effective
      in wound repair and encourages harnessing the potentials of the plant
      biomolecules loaded silver nanoparticle in the treatment of tropical diseases
      including wound healing. 

PMID- 24681225
TI  - PI3K signalling in GnRH actions on dispersed goldfish pituitary cells:
      relationship with PKC-mediated LH and GH release and regulation of long-term
      effects on secretion and total cellular hormone availability.
AB  - Goldfish pituitary cells are exposed to two GnRHs, salmon (s)GnRH and chicken
      (c)GnRH-II. Phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC) both
      participate in acute sGnRH- and cGnRH-II-stimulated LH and GH release. Using
      goldfish pituitary cells, we examined the relationship between PI3K and PKC in
      acute LH and GH secretion, and PI3K involvement in chronic hormone release and
      total LH and GH availability. The PI3K inhibitor LY294002 did not affect PKC
      agonists-induced LH or GH release, and PKC agonists did not alter PI3K p85
      phosphorylation, suggesting PKC activation is not upstream of PI3K in acute
      hormone release. In 2, 6, 12 and 24h treatments, LY294002 did not affect LH
      release but stimulated total LH availability at 6h. sGnRH stimulatory actions on
      LH release and total availability at 12 and 24h, and cGnRH-II effects on these
      parameters at 6h were inhibited by LY294002. LY294002 enhanced basal GH release
      at 2 and 6h, but reduced total GH at 12 and 24h. Increased GH release was seen
      following 6, 12 and 24h of sGnRH, and 2, 6 and 24h of cGnRH-II treatment but
      total GH availability was only elevated by 24h cGnRH-II treatment. Whereas
      LY294002 inhibited GH release responses to sGnRH at 12h and cGnRH-II at 6h, it
      attenuated cGnRH-II-elicited, but not sGnRH-induced, effects on total GH. These
      results indicate that PI3K differentially modulates long-term basal and GnRH
      stimulated hormone release, and total hormone availability, in a time-, cell-type
      , and GnRH isoform-selective manner. 

PMID- 24681226
TI  - Expression pattern of G protein-coupled receptor 30 in human seminiferous tubular
      cells.
AB  - The role of estrogens in male reproductive physiology has been intensively
      studied over the last few years. Yet, the involvement of their specific receptors
      has long been a matter of debate. The selective testicular expression of the
      classic nuclear estrogen receptors (ERalpha and ERbeta) argues in favor of ER
      specific functions in the spermatogenic event. Recently, the existence of a G
      protein-coupled estrogen receptor (GPR30) mediating non-genomic effects of
      estrogens has also been described. However, little is known about the specific
      testicular expression pattern of GPR30, as well as on its participation in the
      control of male reproductive function. Herein, by means of immunohistochemical
      and molecular biology techniques (RT-PCR and Western blot), we aimed to present
      the first exhaustive evaluation of GPR30 expression in non-neoplastic human
      testicular cells. Indeed, we were able to demonstrate that GPR30 was expressed in
      human testicular tissue and that the staining pattern was consistent with its
      cytoplasmic localization. Additionally, by using cultured human Sertoli cells
      (SCs) and isolated haploid and diploid germ cells fractions, we confirmed that
      GPR30 is expressed in SCs and diploid germ cells but not in haploid germ cells.
      This specific expression pattern suggests a role for GPR30 in spermatogenesis.

PMID- 24681227
TI  - Acceptability of immunization in adult contacts of infants: possibility of
      expanding platforms to increase adult vaccine uptake.
AB  - OBJECTIVE: Adult vaccination coverage is low and current strategies are unlikely
      to achieve Healthy People 2020 targets. We determined the attitude of adult
      infant contacts toward recommended adult vaccines and their willingness to
      receive vaccines should they be available during hospital visits or prenatal or
      infant clinic appointments. METHODS: Survey of predominantly Hispanic,
      underinsured and medically underserved infant contacts at a county hospital in
      Houston, Texas where a pertussis cocooning program is offered. RESULTS: Two
      hundred and eighty-five contacts (mean age 32.8 years [18-73]; 94.8% Hispanic)
      participated. Most were fathers (58.2%), followed by aunts (19%), and
      grandparents (12.3%). Participants used many health information sources. 221
      (77.5%) considered healthcare providers the most influential on their decisions
      but only 51.6% reported healthcare visits within the prior year. Forty-one
      (14.4%) discussed family vaccinations during prenatal visits. Preferred locations
      for adult vaccination were hospital or clinic-based (96.5%). Lack of knowledge
      (22.8%), fear of pain/needles (14.7%), work commitments (14%), lack of transport
      (11.2%), cost (10.2%) and fear of side effects (5.3%) were barriers to
      vaccination. More males than females reported fear of pain/needles and work
      commitments (P 0.01 and P 0.02, respectively), and more females lack of transport
      (P<0.001) as barriers. Most planned to (76.1%) or had received (7%) pertussis
      vaccine; if available, 73.3%, 53.3% and 50.5% expressed willingness to receive
      vaccines against influenza, pneumonia and meningitis, respectively. Age,
      ethnicity or education was not associated with willingness to be vaccinated.
      Vaccine acceptance was higher in females than males for pertussis (P 0.04),
      influenza (P 0.008), pneumonia (P 0.04), and meningitis (P 0.006) vaccines by
      multiple regression analysis. CONCLUSIONS: Most adults were willing to be
      vaccinated if offered during hospital visits or clinic appointments for mother or
      infant. Development and expansion of recommended immunization platforms, such as
      the cocooning platform, offers the opportunity to increase adult vaccination
      coverage.

PMID- 24681228
TI  - Immune response to hepatitis B vaccine with high antigen content in non
      responders after standard primary vaccination in Chinese adults.
AB  - CONTEXT: Alternative schedules are needed to provide greater immunogenicity in
      adults who fail to respond to the standard hepatitis B (HB) vaccine regimen.
      OBJECTIVE: To evaluate the immunogenicity and safety of high antigen content HB
      vaccine formulations administered to non-responders after routine primary
      vaccination. DESIGN SETTING, AND PARTICIPANTS: This was a phase III, double
      blind, controlled clinical trial in China. We enrolled healthy participants (16
      60 years old) seronegative for HB surface (HBs) antigen after primary
      vaccination, who had HBs antibody (anti-HBs) titres <10 mIU/ml at 28 days
      following routine vaccination with licensed HB vaccine containing 10 MUg of
      antigen. Participants were randomised (2:2:1) to receive three booster doses of
      HB vaccine formulations containing 60 MUg, 30 MUg or 10 MUg of antigen per dose
      28 days apart. Blood samples were obtained pre-vaccination and 28 days after each
      dose to assess immunogenicity. Reactogenicity and safety were evaluated up to 28
      days after each vaccine dose. RESULTS: Seroconversion rates were >= 92.1% and >=
      87.1% as from the second dose of the 60 MUg and 30 MUg HB vaccine formulations,
      respectively, with geometric mean concentrations (GMCs) of >= 286.0 mIU/ml and >=
      164.0 mIU/ml. In the 10 MUg HB vaccine group the seroconversion rates were >=
      83.0% and the GMCs >= 110.1 mIU/ml as from the second vaccine dose. All HB
      vaccine formulations were well tolerated: 352/1091 (32.3%) participants reported
      at least one injection-site or systemic adverse reaction (145/434 [33.4%] from
      the 60MUg group; 138/435 [31.7%] from the 30 MUg group and 69/222 [31.1%] from
      the 10 MUg group). Most reactions were mild or moderate and resolved within 24h.
      No serious adverse events were reported. CONCLUSION: Booster vaccination with a
      three-dose schedule of a high antigen content HB vaccine formulation was
      immunogenic and well tolerated in healthy adults. Clinicaltrialsgov Identifier:
      NCT01203319.

PMID- 24681229
TI  - Antigen sparing and enhanced protection using a novel rOv-ASP-1 adjuvant in
      aqueous formulation with influenza vaccines.
AB  - Influenza is one of the most common infectious diseases endangering the health of
      humans, especially young children and the elderly. Although vaccination is the
      most effective means of protection against influenza, frequent mutations in viral
      surface antigens, low protective efficacy of the influenza vaccine in the
      elderly, slow production process and the potential of vaccine supply shortage
      during a pandemic are significant limitations of current vaccines. Adjuvants have
      been used to enhance the efficacy of a variety of vaccines; however, no adjuvant
      is included in current influenza vaccines approved in the United States. In this
      study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with
      inactivated influenza vaccine using an aqueous formulation, substantially
      improved the influenza-specific antibody response and protection against lethal
      infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific
      antibody response after immunization with low doses of influenza vaccine,
      allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a
      more rapid response and a stronger Th1-associated antibody response compared to
      vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly,
      rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection
      against challenge with an antigenically distinct strain. These results
      demonstrate that rOv-ASP-1 is an effective adjuvant that: (1) accelerates and
      enhances the specific antibody response induced by influenza vaccine; (2) allows
      for antigen sparing; and (3) augments a Th1-biased and cross-reactive antibody
      response that confers protection against an antigenically distinct strain. 

PMID- 24681230
TI  - Preparation and evaluation of antigen/N-trimethylaminoethylmethacrylate chitosan
      conjugates for nasal immunization.
AB  - The frequent outbreak of respiratory infectious diseases such as influenza and
      pulmonary tuberculosis calls for new immunization strategies with high
      effectiveness. Nasal immunization is one of the most potential methods to prevent
      the diseases infected through the respiratory tract. In this study, we designed a
      water-soluble system based on antigen/N-trimethylaminoethylmethacrylate chitosan
      conjugates for nasal immunization. N-trimethylaminoethylmethacrylate chitosan
      (TMC) was synthesized by free radical polymerization of chitosan and N
      trimethylaminoethylmethacrylate chloride and identified by (1)H NMR and FT-IR.
      Thiolated ovalbumin (OVA) was covalently conjugated to maleimide modified TMC
      with high conjugation efficiency. OVA conjugated TMC (OVA-TMC) significantly
      increased uptake of OVA by Raw 264.7 cells, which was 2.38 times higher than that
      of OVA/TMC physical mixture (OVA+TMC) at 4h. After nasal administration, OVA-TMC
      showed higher transport efficiency to superficial and deep cervical lymph nodes
      than OVA+TMC or OVA alone. Balb/C mice were intranasally given with OVA-TMC three
      times at 2-week internals to evaluate the immunological effect. The serum IgG,
      IgG1 and IgG2a levels of the OVA-TMC group were 17.9-87.9 times higher than that
      of the OVA+TMC group and comparable to that of the intramuscular group. The
      secretory IgA levels in nasal wash and saliva of the OVA-TMC group were 5.2-7.1
      times higher than that of the OVA+TMC group while the secretory IgA levels of the
      intramuscular alum-precipitated OVA group were not increased. After
      immunofluorescence staining of nasal cavity, IgA antibody secreting cells were
      mainly observed in the lamina propria regions and glands of nasal mucosa. OVA-TMC
      showed little toxicity to the nasal epithelia or cilia of rats after nasal
      administration for three consecutive days. These results demonstrated that
      antigen conjugated TMC can induce both systemic and mucosal immune responses
      after nasal administration and may serve as a convenient, safe and effective
      vaccine for preventing respiratory infectious diseases.

PMID- 24681231
TI  - Single particle electron cryo-microscopy of a mammalian ion channel.
AB  - The transient receptor potential (TRP) ion channel family is large and
      functionally diverse, second only to potassium channels. Despite their prominence
      within the animal kingdom, TRP channels have resisted crystallization and
      structural determination for many years. This barrier was recently broken when
      the three-dimensional structure of the vanilloid receptor 1 (TRPV1) was
      determined by single particle electron cryo-microscopy (cryo-EM). Moreover, this
      is the first example in which the near atomic resolution structure of an integral
      membrane protein was elucidated by this technique and in a manner not requiring
      crystals, demonstrating the transformative power of single particle cryo-EM for
      revealing high-resolution structures of integral membrane proteins, particularly
      those of mammalian origin. Here we summarize technical advances, in both
      biochemistry and cryo-EM, that led to this major breakthrough.

PMID- 24681232
TI  - Single-port laparoscopically assisted transumbilical ultraminilaparotomic
      myomectomy.
AB  - The objective of this prospective observational study, performed in a university
      hospital and a tertiary care center, was to describe the surgical technique and
      our initial experience with single-port laparoscopically assisted transumbilical
      ultraminilaparotomic myomectomy (SPLA-TUM). During July and August 2012, 15 women
      with symptomatic subserosal or superficial intramural myomas (<= 8 cm) underwent
      SPLA-TUM. Mean (SD) operative time was 64.9 (9.5) minutes, hemoglobin change was
      1.2 (0.5) g/dL, return of bowel activity was 32.8 (3.5) hours, and length of
      hospital stay was 3.1 (0.4) days. In 1 patient (6.7%), SPLA-TUM did not provide a
      satisfactory surgical field, and thus the procedure was converted to single-port
      laparoscopic myomectomy. There were no surgical or wound complications. Compared
      with single-port laparoscopic myomectomy, SPLA-TUM, which was designed by
      integrating the surgical techniques of single-port laparoscopy and laparotomy,
      can reduce operative time by enabling comfortable suturing and reliable knot
      tying while maintaining the advantages of single-port laparoscopy. SPLA-TUM is a
      feasible alternative in selected patients with symptomatic myomas.

PMID- 24681233
TI  - Immune and stress mediators in response to bilateral adnexectomy: comparison of
      single-port access and conventional laparoscopy in a porcine model.
AB  - STUDY OBJECTIVE: To evaluate systemic markers of immune and stress responses
      after bilateral adnexectomy performed using 2 different laparoscopic techniques
      in pigs. DESIGN: Prospective comparative study (Canadian Task Force
      classification II-2). SETTING: University teaching hospital, research hospital,
      and tertiary care center. ANIMALS: Twenty female Yorkshire pigs undergoing
      laparoscopic surgery. INTERVENTIONS: Animals underwent bilateral salpingo
      oophorectomy (ovary and fallopian tube extraction), performed via conventional
      laparoscopy (n = 10) or the single-port access approach (n = 10). MEASUREMENTS
      AND MAIN RESULTS: Injury provokes an acute-phase response, primarily produced by
      cytokines. The inflammatory response has been well described for major surgery
      and for conventional laparoscopy; however, little information is currently
      available for single-port laparoscopy, and none in the gynecologic field. This is
      the first study to compare serum cytokine interleukin 6 (IL-6) and tumor necrosis
      factor alpha (TNF-alpha) concentrations at baseline and in the early
      postoperative period (2, 4, and 20 hours) after bilateral salpingo-oophorectomy
      performed via conventional laparoscopy (n = 10) or single-port access (n = 10) in
      a porcine model. The stress response was measured using glucose and cortisol
      concentrations and the animals' response to surgery via a 6-category observation
      based behavior test. Both IL-6 and TNF-alpha concentrations peaked at 4 hours
      after surgery, and were significantly lower in the single-port access group (p =
      .02) than in the conventional laparoscopy group (p = .02). In addition, in the
      single-port access group, concentrations of stress markers were slightly lower at
      all intervals recorded and were statistically significant at 2 hours after the
      operation for glucose concentration (mean [SD], 164.50 [26.73] mg/dL for
      conventional laparoscopy vs 86.50 [17.93] mg/dL for single-port access; p = .02).
      CONCLUSION: Evidence of improved inflammatory and stress responses was recorded
      in the minimally invasive single-port group. More clinical investigations are
      needed to further study the applicability of single-port access laparoscopy in
      gynecologic surgery.

PMID- 24681234
TI  - Investigating the role for adaptation of the microbial community to transform
      trace organic chemicals during managed aquifer recharge.
AB  - This study was undertaken to investigate whether adaptation by pre-exposure to
      trace organic chemicals (TOrCs) was necessary for microbial transformation during
      managed aquifer recharge (MAR). Two pairs of laboratory-scale soil columns, each
      receiving a different primary substrate, were utilized to simulate the dominant
      bulk organic carbon present in MAR systems receiving wastewater effluent of
      varying quality and having undergone different degrees of pre-treatment, as well
      as organic carbon prevalent at different stages of subsurface travel. Each pair
      of columns consisted of duplicate set-ups receiving the same feed solution with
      only one pre-exposed to a suite of eight TOrCs for approximately ten months.
      Following the pre-exposure period, a spiking experiment was conducted in which
      the non-exposed columns also received the same suite of TOrCs. TOrC attenuation
      was quantified for the pre- and non-exposed columns of each pair during the
      spiking experiment. The microbial community structure and function of these
      systems were characterized by pyrosequencing of 16S rRNA gene and metagenomics,
      respectively. Biotransformation rather than sorption was identified as the
      dominant removal mechanism for almost all the TOrCs (except triclocarban).
      Similar removal efficiencies were observed between pre-exposed and non-exposed
      columns for most TOrCs. No obvious differences in microbial community structure
      were revealed between pre- and non-exposed columns. Using metagenomics,
      biotransformation capacity potentials of the microbial community present were
      also similar between pre- and non-exposed columns of each pair. Overall, the pre
      exposure of MAR systems to TOrCs at ng/L levels did not affect their attenuation
      and had no obvious influence on the resulting microbial community structure and
      function. Thus, other factors such as bioavailability of the primary substrate
      play a greater role regarding biotransformation of TOrCs. These results indicate
      that MAR systems adapted to a primary substrate are capable of degrading TOrC
      without necessarily being pre-exposed to them, making MAR a robust treatment
      barrier for biodegradable TOrCs. 

PMID- 24681235
TI  - Clear as mud: a meta-analysis on the effects of sedimentation on freshwater fish
      and the effectiveness of sediment-control measures.
AB  - Increase in fine sediments in freshwater resulting from anthropogenic development
      is a potential stressor for fish and thus may cause population declines. Though a
      large body of literature exists on the topic, there have been few attempts to
      synthesize this information in a quantitative manner. Through meta-analysis we
      investigated the effects of sediment in lotic environments on resident
      ichthyofauna using ecologically-relevant endpoints for tolerant (e.g., northern
      pike Esox lucius) and intolerant (e.g., brook trout Salvelinus fontinalis)
      species. Further, the efficiency of sediment-control devices was explored to
      inform mitigation measures. An increase in suspended and deposited sediments was
      demonstrated to have a negative effect on all parameters and tolerances tested
      (feeding behavior [feeding rate, reaction distance to food item]; spawning
      success [survival of fry to eyed stage, fry emergence]; species richness; P <
      0.001) except fish abundance (P = 0.058). Heterogeneity between studies was a
      factor in all analyses. Although there were insufficient studies to conduct meta
      analysis on sediment-control devices, weighted percent efficiency estimates
      revealed that properly installed sediment-control fences tended to have a higher
      percent efficiency (73-80%) than sediment traps and basins (40-52%). These
      results highlight the negative impact that increases in suspended and deposited
      sediments can have on resident fishes from the individual to the population, and
      the need for more transparent and thorough statistical reporting. The analysis
      also identifies a clear need for rigorous experimental studies contrasting
      different sediment-control devices and strategies given that little such work has
      been published. That alone is remarkable given that sediment-control devices are
      often a requirement of regulators for riparian development activities, yet the
      evidence to support the effectiveness of the primary mitigative strategies is
      weak. 

PMID- 24681236
TI  - Gut hormones--team workers or solo trippers?

PMID- 24681238
TI  - Differential effects of fucoidans with low and high molecular weight on the
      viability and function of spleen cells.
AB  - Fucoidan is an edible sulfated polysaccharide purified from brown algae that has
      multiple biological activities. However, the effects of fucoidans of different
      molecular weights on immune cells have not been determined. Thus, we treated
      spleen cells with low- and high-molecular-weight fucoidans (LMF and HMF,
      respectively). Viability assays demonstrated that HMF enhanced the viability and
      prevented the death of spleen cells. Furthermore, functional analysis revealed
      that HMF significantly increased the production of interferon-gamma and nitric
      oxide. In contrast, LMF had low activity and was relatively toxic to spleen
      cells. Taken together, these results indicate that HMF makes the greatest
      contribution to the immunostimulatory activity of fucoidan mixtures.
      Additionally, fucoidans with different molecular weights may have different
      effects on the viability and function of immune cells. This study increases our
      understanding of fucoidans, and may broaden their use in the basic research and
      clinical fields. 

PMID- 24681237
TI  - Resistance of Biomphalaria glabrata 13-16-R1 snails to Schistosoma mansoni PR1 is
      a function of haemocyte abundance and constitutive levels of specific transcripts
      in haemocytes.
AB  - Continuing transmission of human intestinal schistosomiasis depends on the
      parasite's access to susceptible snail intermediate hosts (often Biomphalaria
      glabrata). Transmission fails when parasite larvae enter resistant individuals in
      wild snail populations. The genetic basis for differences in snail
      susceptibility/resistance is being intensively investigated as a means to devise
      novel control strategies based on resistance genes. Reactive oxygen species
      produced by the snail's defence cells (haemocytes) are effectors of resistance.
      We hypothesised that genes relevant to production and consumption of reactive
      oxygen species would be expressed differentially in the haemocytes of snail hosts
      with different susceptibility/resistance phenotypes. By restricting the genetic
      diversity of snails, we sought to facilitate identification of resistance genes.
      By inbreeding, we procured from a 13-16-R1 snail population with both susceptible
      and resistant individuals 52 lines of B. glabrata (expected homozygosity ~87.5%),
      and determined the phenotype of each in regard to susceptibility/resistance to
      Schistosoma mansoni. The inbred lines were found to have line-specific
      differences in numbers of spreading haemocytes; these were enumerated in both
      juvenile and adult snails. Lines with high cell numbers were invariably resistant
      to S. mansoni, whereas lines with lower cell numbers could be resistant or
      susceptible. Transcript levels in haemocytes were quantified for 18 potentially
      defence-related genes. Among snails with low cell numbers, the different
      susceptibility/resistance phenotypes correlated with differences in transcript
      levels for two redox-relevant genes: an inferred phagocyte oxidase component and
      a peroxiredoxin. Allograft inflammatory factor (potentially a regulator of
      leucocyte activation) was expressed at higher levels in resistant snails
      regardless of spread cell number. Having abundant spreading haemocytes is
      inferred to enable a snail to kill parasite sporocysts. In contrast, snails with
      fewer spreading haemocytes seem to achieve resistance only if specific genes are
      expressed constitutively at levels that are high for the species.

PMID- 24681239
TI  - Attitudes toward vaccination and the H1N1 vaccine: poor people's unfounded fears
      or legitimate concerns of the elite?
AB  - In 2009-2010, the H1N1 episode occurred in a general context of decreasing public
      confidence in vaccination. We assumed opposition to vaccination in general to be
      an 'unfounded fear', reflecting ignorance and perceived vulnerability among low
      socioeconomic status (SES) people, and opposition to the H1N1 vaccine a
      'legitimate concern' reflecting the elite's commitment to 'risk culture' in a
      'risk society'. We indirectly tested these assumptions by investigating the
      socioeconomic profiles associated with opposition to vaccination in general and
      opposition to the H1N1 vaccine specifically. Our second aim was to determine
      whether or not opposition to the H1N1 vaccine fuelled opposition to vaccination
      in general. We used data from a telephone survey conducted in 2009-2010 among a
      random sample of French people aged 15-79 (N = 9480). Attitudes toward
      vaccination in general and toward the H1N1 vaccine specifically varied
      significantly between October 2009 and June 2010 with strong correlation being
      observed between these attitudes throughout the whole period. In multivariable
      analysis attitudes toward vaccination in general remained a significant predictor
      of attitudes to the H1N1 vaccine and vice versa, for distinct profiles as
      follows: males, older people, low-SES people for opposition to vaccination in
      general, versus females, people aged 35-49 and those with an intermediate SES for
      opposition to the H1N1 vaccine. Results also differed regarding indicators of
      social vulnerability, proximity to preventive medicine and vaccination history.
      The first profile supported the "unfounded fears expressed by low-SES people"
      hypothesis, while the second echoed previous work related to middle-classes'
      "healthism". Opposition to vaccination should not be reduced to irrational
      reactions reflecting ignorance or misinformation and further research is needed
      to acquire a greater understanding of the motives of opponents.

PMID- 24681240
TI  - Inhibition of kidney ischemia-reperfusion injury through local infusion of a TLR2
      blocker.
AB  - Kidney ischemia-reperfusion injury (IRI) occurs as a result of complex
      interactions of kidney parenchymal cells and immune cells that are initiated by
      hypoxic damage of parenchymal cells. In particular, tubular epithelial cells
      (TECs) not only are susceptible to ischemia but also have an auto-loop system to
      amplify renal inflammation caused by ischemia and reperfusion. Since endogenous
      TLR2 ligands released from TECs trigger renal inflammation leading to kidney IRI
      in an autocrine manner, we hypothesized that local infusion of TLR2 blockers
      would prevent kidney IRI. In this study, we demonstrated that injection of
      antagonist anti-TLR2 mAb through the renal vein after cross-clamping
      significantly reduced the recruitment of NK cells to the kidney after IRI, a
      phenomenon that is governed by TLR2 signaling in TECs. In addition, intrarenal
      blocking of TLR2 signaling was shown to inhibit NK cell-mediated neutrophil
      infiltration and subsequent renal damage. Overall, our simple experiment system
      will be of help in testing the efficacy of candidate blockers targeting kidney
      parenchymal cells in inhibition of kidney IRI. 

PMID- 24681241
TI  - Preventing intense false positive and negative reactions attributed to the
      principle of ELISA to re-investigate antibody studies in autoimmune diseases.
AB  - To study the possible involvement of potential environmental pathogens in the
      pathogenesis of autoimmune diseases, it is essential to investigate antibody
      responses to a variety of environmental agents and autologous components.
      However, none of the conventional ELISA buffers can prevent the false positive
      and negative reactions attributed to its principal, which utilizes the high
      binding affinity of proteins to plastic surfaces. The aims of this study are to
      reveal all types of non-specific reactions associated with conventional buffer
      systems, and to re-investigate antibody responses to potential environmental
      pathogenic and autologous antigens in patients with autoimmune diseases using a
      newly developed buffer system "ChonBlockTM" by ELISA. Compared to conventional
      buffers, the new buffer was highly effective in reducing the most intense false
      positive reaction caused by hydrophobic binding of immunoglobulin in sample
      specimens to plastic surfaces, "background (BG) noise reaction", and other non
      specific reactions without interfering with antigen-antibody reactions. Applying
      this buffer, we found that IgG antibody responses to Escherichia coli O111:B4, E.
      coli lipopolysaccharide (LPS) and peptidoglycan polysaccharide (PG-PS) were
      significantly lower or tended to be lower in patients with rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE), whereas IgA antibody responses to
      these antigens were equal or tended to be higher compared to normal controls. As
      a consequence, the IgA/IgG antibody ratios against these agents were
      significantly higher in patients with RA and SLE, except for Crohn's disease,
      which showed significantly higher IgG responses to these antigens. To assay
      antibodies in human sera, it is indispensable to eliminate false positive and
      negative reactions by using an appropriate buffer system, and to include antigen
      non-coated blank wells to determine BG noise reactions of invidual samples.
      Finally, based on our preliminary analysis in this study, we propose that low IgG
      antibody responses to potential pathogenic environmental factors may be the
      fundamental disorder in autoimmune diseases. 

PMID- 24681242
TI  - Adapting in vitro embryonic stem cell differentiation to the study of locus
      control regions.
AB  - Numerous locus control region (LCR) activities have been discovered in gene loci
      important to immune cell development and function. LCRs are a distinct class of
      cis-acting gene regulatory elements that appear to contain all the DNA sequence
      information required to establish an independently and predictably regulated gene
      expression program at any genomic site in native chromatin of a whole animal. As
      such, LCR-regulated transgenic reporter systems provide invaluable opportunities
      to investigate the mechanisms of gene regulatory DNA action during development.
      Furthermore the qualities of LCR-driven gene expression, including spatiotemporal
      specificity and "integration site-independence" would be highly desirable to
      incorporate into vectors used in therapeutic genetic engineering. Thus,
      advancement in the methods used to investigate LCRs is of considerable basic and
      translational significance. We study the LCR present in the mouse T cell receptor
      (TCR)-alpha gene locus. Until recently, transgenic mice provided the only
      experimental model capable of supporting the entire spectrum of LCR activities.
      We have recently reported complete manifestation of TCRalpha LCR function in T
      cells derived in vitro from mouse embryonic stem cells (ESC), thus validating a
      complete cell culture model for the full range of LCR activities seen in
      transgenic mice. Here we discuss the critical parameters involved in studying LCR
      regulated gene expression during in vitro hematopoietic differentiation from
      ESCs. This advance provides an approach to speed progress in the LCR field, and
      facilitate the clinical application of its findings, particularly to the genetic
      engineering of T cells. 

PMID- 24681243
TI  - Higher-order cognitive factors affect subjective but not proprioceptive aspects
      of self-representation in the rubber hand illusion.
AB  - In the current study we look at whether subjective and proprioceptive aspects of
      selfrepresentation are separable components subserved by distinct systems of
      multisensory integration. We used the rubber hand illusion (RHI) to draw the
      location of the 'self' away from the body, towards extracorporeal space (Out
      Condition), thereby violating top-down information about the body location. This
      was compared with the traditional RHI which drew position of the 'self' towards
      the body (In Condition). We were successfully able to draw proprioceptive
      position of the limbs in and out from the body suggesting body perception is a
      purely bottom-up process, resistant to top-down effects. Conversely, we found
      subjective self-representation was altered by the violation of top-down body
      information - as the strong association of subjective and proprioceptive factors
      found in the In Condition became non-significant in the Out Condition.
      Interestingly, we also found evidence that subjective embodiment can modulate
      tactile perception. 

PMID- 24681244
TI  - Fluctuations in pre-trial attentional state and their influence on goal neglect.
AB  - Fluctuations in attentional state and their relation to goal neglect were
      examined in the current study. Participants performed a variant of the Stroop
      task in which attentional state ratings were given prior to each trial. It was
      found that pre-trial attentional state ratings predicted subsequent trial
      performance, such that when participants rated their current attentional state as
      highly focused on the current task, performance tended to be high compared to
      when participants reported their current attentional state as being unfocused on
      the current task. This effect was larger for incongruent than congruent trials
      leading to differences in the magnitude of the Stroop effect as a function of pre
      trial attentional state. Furthermore, variability in attentional state was
      correlated with overall levels of performance, and when attentional state was
      covaried out, the Stroop effect was greatly reduced. These results suggest a link
      between fluctuations in pre-trial attentional state and goal neglect. 

PMID- 24681245
TI  - Trial effects in single-trial ERP components and autonomic responses at very long
      ISIs.
AB  - Single-trial data from autonomic and ERP measures were used to capture the
      rapidly decreasing initial responses characteristic of the orienting reflex (OR)
      to repeated stimuli. Stimulus-response patterns were compared to determine
      central analogues of autonomic indices of processes leading to the OR, and the OR
      itself. Participants were presented with 12 indifferent tones in an auditory
      dishabituation paradigm. Temporal principal component analysis (PCA) decomposed
      EOG-corrected ERP data for 16 subjects. Response patterns of ERPs, cardiac, and
      respiratory responses were compared to the phasic skin conductance response
      (SCR). SCR decremented over trials, recovered on the change trial, and
      dishabituated to the representation of the standard, meeting the formal
      definition of habituation required of the OR. The evoked cardiac response showed
      no trial effects. Respiratory pause (RP) decreased linearly over trials,
      recovering marginally on the change trial. Nine identifiable ERP components were
      extracted: P1, N1-3, N1-1, processing negativity (PN), P2, P3a, P3b, a novelty
      sensitive P3 component (labelled HabP3), and the slow wave (SW). P3b and SW
      showed decrement over trials, but with no recovery, HabP3 showed decrement and
      increased response on the change trial, while the P1, N1 subcomponents, P2 and
      P3a were insensitive to novelty. Stimulus-response patterns of the RP and HabP3
      suggest sensitivity to novelty processing, while the P1, N1-3, N-1, PN, P2, P3a
      and cardiac deceleration appear to mark processing prior to novelty, such as
      stimulus transient detection (cardiac deceleration) and/or intensity processing.
      This study supports predictions of preliminary process theory, demonstrating
      fractionation of 3 autonomic and 9 ERP components to novelty, and disconfirming
      the unitary nature of the OR.

PMID- 24681246
TI  - Immediate effects of Alpha/theta and Sensory-Motor Rhythm feedback on music
      performance.
AB  - This is one of a series of investigations comparing two EEG-neurofeedback
      protocols - Alpha/theta (A/T) and Sensory-Motor Rhythm (SMR) - for performance
      enhancement in the Arts, here with the focus on music. The original report (Egner
      and Gruzelier, 2003) established a beneficial outcome for elite conservatoire
      musicians following A/T training in two investigations. Subsequently this A/T
      advantage was replicated for both advanced instrumental and novice singing
      abilities, including improvisation, while SMR training benefited novice
      performance only (Gruzelier, Holmes et al., 2014). Here we report a replication
      of the latter study in university instrumentalists who as before were novice
      singers with one design change - post-training performances were conducted within
      the tenth final session instead of on a subsequent occasion. As before expert
      judges rated the domains of Creativity/Musicality, Communication/Presentation and
      Technique. The proximity to training of the music performances within the last
      session likely compromised gains from A/T learning, but perhaps reinforced the
      impact of SMR training efficacy. In support of validation there was evidence of
      strong within- and across-session A/T learning and positive linear trends for
      across-session SMR/theta and SMR/beta-2 ratio learning. In support of mediation
      learning correlated with music performance. The A/T outcome was markedly
      discrepant from previous studies and should dispel any impression that the
      hypnogogic state itself is transferred to the performance context. The effects of
      SMR ratio training are consistent with an impact on lower-order abilities
      required in novice performance such as sustained attention and memory, and
      benefiting all three domains of music assessment. 

PMID- 24681247
TI  - Mismatch negativity indexes illness-specific impairments of cortical plasticity
      in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease.
AB  - Cognitive impairment is an important predictor of functional outcome in patients
      with schizophrenia, yet its neurobiology is still incompletely understood.
      Neuropathological evidence of impaired synaptic connectivity and NMDA receptor
      dependent transmission in superior temporal cortex motivated us to explore the
      correlation of in vivo mismatch negativity (MMN) with cognitive status in
      patients with schizophrenia. MMN elicited in a roving stimulus paradigm displayed
      a response proportional to the number of stimulus repetitions (memory trace
      effect). Preliminary evidence in patients with chronic schizophrenia suggests
      that attenuation of this MMN memory trace effect was correlated with the degree
      of neuropsychological memory dysfunction. Here we present data from a larger
      confirmatory study in patients with schizophrenia, bipolar disorder, probable
      Alzheimer's disease and healthy controls. We observed that the diminution of the
      MMN memory trace effect and its correlation with memory impairment was only found
      in the schizophrenia group. Recent pharmacological studies using the roving
      paradigm suggest that attenuation of the MMN trace effect can be understood as
      abnormal modulation of NMDA receptor-dependent plasticity. We suggest that the
      convergence of the previously identified synaptic pathology in supragranular
      cortical layers with the intracortical locus of MMN generation accounts for the
      remarkable robustness of MMN impairments in schizophrenia. We further speculate
      that this layer-specific synaptic pathology identified in supragranular neurons
      plays a pivotal computational role, by weakening the encoding and propagation of
      prediction errors to higher cortical modules. According to predictive coding
      theory such breakdown will have grave implications not only for perception, but
      also for higher-order cognition and may thus account for the MMN-cognition
      correlations observed here. Finally, MMN is a sensitive and specific biomarker
      for detecting the early prodromal phase of schizophrenia and is well suited for
      the exploration of novel cognition-enhancing agents in humans. 

PMID- 24681248
TI  - The liver is a peculiar organ when it comes to stem cells.
AB  - This Commentary highlights the article by Sekiya and Suzuki, detailing genetic
      lineage tracing to determine the origin of cells that form primitive ductules in
      a mouse model of chronic liver injury. 

PMID- 24681250
TI  - Interleukin-1beta induced activation of the hypothalamus-pituitary-adrenal axis
      is dependent on interleukin-1 receptors on non-hematopoietic cells.
AB  - The proinflammatory cytokine interleukin-1beta (IL-1beta) plays a major role in
      the signal transduction of immune stimuli from the periphery to the central
      nervous system, and has been shown to be an important mediator of the immune
      induced stress hormone release. The signaling pathway by which IL-1beta exerts
      this function involves the blood-brain-barrier and induced central prostaglandin
      synthesis, but the identity of the blood-brain-barrier cells responsible for this
      signal transduction has been unclear, with both endothelial cells and
      perivascular macrophages suggested as critical components. Here, using an
      irradiation and transplantation strategy, we generated mice expressing IL-1 type
      1 receptors (IL-1R1) either in hematopoietic or non-hematopoietic cells and
      subjected these mice to peripheral immune challenge with IL-1beta. Following both
      intraperitoneal and intravenous administration of IL-1beta, mice lacking IL-1R1
      in hematopoietic cells showed induced expression of the activity marker c-Fos in
      the paraventricular hypothalamic nucleus, and increased plasma levels of ACTH and
      corticosterone. In contrast, these responses were not observed in mice with IL
      1R1 expression only in hematopoietic cells. Immunoreactivity for IL-1R1 was
      detected in brain vascular cells that displayed induced expression of the
      prostaglandin synthesizing enzyme cyclooxygenase-2 and that were immunoreactive
      for the endothelial cell marker CD31, but was not seen in cells positive for the
      brain macrophage marker CD206. These results imply that activation of the HPA
      axis by IL-1beta is dependent on IL-1R1s on non-hematopoietic cells, such as
      brain endothelial cells, and that IL-1R1 on perivascular macrophages are not
      involved. 

PMID- 24681249
TI  - Quantitatively controlling expression of miR-17~92 determines colon tumor
      progression in a mouse tumor model.
AB  - The miRNA cluster miR-17~92 targets mRNAs involved in distinct pathways that
      either promote or inhibit tumor progression. However, the cellular and molecular
      mechanisms underlying miR-17~92 cluster-mediated protumorigenic or anti
      tumorigenic effects have not been studied. Herein, we determined that inhibition
      of colon cancer progression is dictated by quantitatively controlling expression
      of the miR-17~92 cluster. miR-19 in the context of the miR-17~92 cluster at
      medium levels promoted tumor metastasis through induction of Wnt/beta-catenin
      mediated epithelial-mesenchymal transition by targeting to the tumor-suppressor
      gene, PTEN. However, higher levels of the miR-17~92 cluster switched from PTEN to
      oncogenes, including Ctnnb1 (beta-catenin) via miR-18a, which resulted in
      inhibition of tumor growth and metastasis. However, overexpression of Ctnnb1in
      tumor cells with high-level miR-17~92 did not lead to an increase in the levels
      of beta-catenin protein, suggesting that other factors regulated by higher levels
      of miR-17~92 might also contribute to inhibition of tumor growth and metastasis.
      Those unidentified factors may negatively regulate the production of beta-catenin
      protein. Collectively, the data presented in this study revealed that higher
      levels of miR-17~92 were a critical negative regulator for activation of the
      Wnt/beta-catenin pathway and could have a potential therapeutic application.

PMID- 24681251
TI  - Diet-induced obesity progressively alters cognition, anxiety-like behavior and
      lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine
      2,3-dioxygenase activation.
AB  - Obesity is associated with a high prevalence of mood symptoms and cognitive
      dysfunctions that emerges as significant risk factors for important health
      complications such as cardiovascular diseases and type 2 diabetes. It is
      therefore important to identify the dynamic of development and the
      pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity
      is also associated with peripheral low-grade inflammation and increased
      susceptibility to immune-mediated diseases. Excessive production of
      proinflammatory cytokines and the resulting activation of the brain tryptophan
      catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote
      neurobehavioral complications, particularly depression. In that context,
      questions arise about the impact of diet-induced obesity on the onset of
      neuropsychiatric alterations and the increased susceptibility to immune-mediated
      diseases displayed by obese patients, particularly through brain IDO activation.
      To answer these questions, we used C57Bl/6 mice exposed to standard diet or
      western diet (WD; consisting of palatable energy-dense food) since weaning and
      for 20 weeks. We then measured inflammatory and behavioral responses to a
      systemic immune challenge with lipopolysaccharide (LPS) in experimental
      conditions known to alter cognitive and emotional behaviors independently of any
      motor impairment. We first showed that in absence of LPS, 9 weeks of WD is
      sufficient to impair spatial recognition memory (in the Y-maze). On the other
      hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze),
      but did not affect depressive-like behavior (in the tail-suspension and forced
      swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior
      compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic
      proinflammatory cytokine expression and brain IDO activation. Taken together,
      these results show that WD exposure alters cognition and anxiety in unstimulated
      conditions and enhances activation of neurobiological mechanisms underlying
      depression after immune stimulation. They suggest therefore that obesity, and
      possibly obesity-associated inflammatory priming, may represent a vulnerability
      state to immune-mediated depressive symptoms.

PMID- 24681252
TI  - CX3CL1-mediated macrophage activation contributed to paclitaxel-induced DRG
      neuronal apoptosis and painful peripheral neuropathy.
AB  - Painful peripheral neuropathy is a dose-limiting side effect of paclitaxel
      therapy, which hampers the optimal clinical management of chemotherapy in cancer
      patients. Currently the underlying mechanisms remain largely unknown. Here we
      showed that the clinically relevant dose of paclitaxel (3*8mg/kg, cumulative dose
      24mg/kg) induced significant upregulation of the chemokine CX3CL1 in the A-fiber
      primary sensory neurons in vivo and in vitro and infiltration of macrophages into
      the dorsal root ganglion (DRG) in rats. Paclitaxel treatment also increased
      cleaved caspase-3 expression, induced the loss of primary afferent terminal
      fibers and decreased sciatic-evoked A-fiber responses in the spinal dorsal horn,
      indicating DRG neuronal apoptosis induced by paclitaxel. In addition, the
      paclitaxel-induced DRG neuronal apoptosis occurred exclusively in the presence of
      macrophage in vitro study. Intrathecal or systemic injection of CX3CL1
      neutralizing antibody blocked paclitaxel-induced macrophage recruitment and
      neuronal apoptosis in the DRG, and also attenuated paclitaxel-induced allodynia.
      Furthermore, depletion of macrophage by systemic administration of clodronate
      inhibited paclitaxel-induced allodynia. Blocking CX3CL1 decreased activation of
      p38 MAPK in the macrophage, and inhibition of p38 MAPK activity blocked the
      neuronal apoptosis and development of mechanical allodynia induced by paclitaxel.
      These findings provide novel evidence that CX3CL1-recruited macrophage
      contributed to paclitaxel-induced DRG neuronal apoptosis and painful peripheral
      neuropathy. 

PMID- 24681253
TI  - Ligustilide ameliorates neuroinflammation and brain injury in focal cerebral
      ischemia/reperfusion rats: involvement of inhibition of TLR4/peroxiredoxin 6
      signaling.
AB  - Blocking TLR4/peroxiredoxin (Prx6) signaling is proposed to be a novel
      therapeutic strategy for ischemic stroke because extracellular Prx6 released from
      ischemic cells may act as an endogenous ligand for TLR4 and initiate destructive
      immune responses in ischemic brain. Our previous studies showed that ligustilide
      (LIG) exerted antineuroinflammatory and neuroprotective effects against ischemic
      insult, but the underlying mechanisms remain unclear. This study investigated
      whether the TLR4/Prx6 pathway is involved in the protective effect of LIG against
      postischemic neuroinflammation and brain injury induced by transient middle
      cerebral artery occlusion (MCAO) in rats. Intraperitoneal LIG administration (20
      and 40 mg/kg/day) at reperfusion onset after MCAO resulted in a reduction of
      brain infarct size and improved neurological outcome over 72 h. LIG-induced
      neuroprotection was accompanied by improvement of neuropathological alterations,
      including neuron loss, astrocyte and microglia/macrophage activation, neutrophil
      and T-lymphocyte invasion, and regulation of inflammatory mediators expression.
      Moreover, LIG significantly inhibited the expression and extracellular release of
      Prx6 and activation of TLR4 signaling, reflected by decreased TLR4 expression,
      extracellular signal-regulated kinase 1/2 phosphorylation, and transcriptional
      activity of NF-kappaB and signal transducer and activator of transcription 3 in
      the ischemic brain. Our results demonstrate that LIG may provide an early and
      direct neuroprotection by inhibiting TLR4/Prx6 signaling and subsequent immunity
      and neuroinflammation after cerebral ischemia. These findings support the
      translational potential of blocking TLR4/Prx6 signaling for the treatment of
      ischemic stroke.

PMID- 24681254
TI  - Involvement of oxidative stress in 4-vinylcyclohexene-induced toxicity in
      Drosophila melanogaster.
AB  - 4-Vinylcyclohexene (VCH) is a dimer of 1,3-butadiene produced as a by-product of
      pesticides, plastic, rubber, flame retardants, and tire production. Although,
      several studies have reported the ovotoxicity of VCH, information on a possible
      involvement of oxidative stress in the toxicity of this occupational chemical is
      scarce. Hence, this study was carried out to investigate further possible
      mechanisms of toxicity of VCH with a specific emphasis on oxidative stress using
      a Drosophila melanogaster model. D. melanogaster (both genders) of 1 to 3 days
      old were exposed to different concentrations of VCH (10 uM-1 mM) in the diet for
      5 days. Subsequently, the survival and negative geotaxis assays and the
      quantification of reactive oxygen species (ROS) generation were determined. In
      addition, we evaluated RT-PCR expressions of selected oxidative stress and
      antioxidant mRNA genes (HSP27, 70, and 83, SOD, Nrf-2, MAPK2, and catalase).
      Furthermore, catalase, glutathione-S-transferase (GST), delta aminolevulinic acid
      dehydratase (delta-ALA-D), and acetylcholinesterase (AChE) activities were
      determined. VCH exposure impaired negative geotaxic behavior and induced the mRNA
      of SOD, Nrf-2, and MAPK2 genes expressions. There were increases in catalase and
      ROS production, as well as inhibitions of GST, delta-ALA-D, and AChE activities
      (P<0.05). Our results suggest that the VCH mechanism of toxicity is associated
      with oxidative damage, as evidenced by the alteration in the oxidative stress
      antioxidant balance, and possible neurotoxic consequences due to decreased AChE
      activity, and impairments in negative geotaxic behavior. Thus, we conclude that
      D. melanogaster is a useful model for investigating the toxicity of VCH exposure,
      and here, we have provided further insights on the mechanism of VCH-induced
      toxicity.

PMID- 24681255
TI  - DJ-1 mediates the resistance of cancer cells to dihydroartemisinin through
      reactive oxygen species removal.
AB  - Dihydroartemisinin (DHA), one of the main metabolites of artemisinin and its
      derivatives, presents anti-cancer potential in vitro and in vivo. To explore the
      mechanisms of resistance toward DHA, a DHA-resistant cell line, HeLa/DHA, was
      established with a resistance factor of 7.26 in vitro. Upon DHA treatment,
      apoptotic cells were significantly elicited in parental HeLa cells but minimally
      induced in HeLa/DHA cells. HeLa/DHA cells also displayed much less sensitivity to
      DHA-induced tumor suppression in cancer xenograft models than HeLa cells.
      Intriguingly, DHA-resistant cells did not display a multidrug-resistant
      phenotype. Based on a proteomic study employing LC-ESI-MS/MS together with
      pathway analysis, DJ-1 (PARK7) was found to be highly expressed in HeLa/DHA
      cells. Western blot and immunofluorescence assays confirmed the higher expression
      of DJ-1 in HeLa/DHA cells than in parental cells in both cell line and xenograft
      models. DJ-1 is translocated to the mitochondria of HeLa/DHA cells and oxidized,
      providing DJ-1 with stronger cytoprotection activity. Further study revealed that
      DJ-1 knockdown in HeLa/DHA cells abolished the observed resistance, whereas
      overexpression of DJ-1 endowed the parental HeLa cells with resistance toward
      DHA. Reactive oxygen species (ROS) were also significantly induced by either DHA
      or hydrogen peroxide in HeLa cells but not in resistant HeLa/DHA cells. When the
      cells were pretreated with N-acetyl-l-cysteine, the effect of DJ-1 knockdown on
      sensitizing HeLa/DHA cells to DHA was significantly attenuated. In summary, our
      study suggests that overexpression and mitochondrial translocation of DJ-1
      provides HeLa/DHA cells with resistance to DHA-induced ROS and apoptosis. 

PMID- 24681257
TI  - Reactive oxygen species are physiological mediators of the noradrenergic
      signaling pathway in the mouse supraoptic nucleus.
AB  - Free radicals are essential for the vasopressin (AVP) response to plasmatic
      hyperosmolarity. Noradrenergic afferents are the major projections on the
      supraoptic nucleus (SON) of the hypothalamus and stimulate the expression of AVP
      via a nitric oxide (NO) pathway. In this study, we investigated the mechanisms
      linking free radicals and noradrenaline (NA)-induced regulation of AVP. Analysis
      of Tg8 transgenic mice, invalidated for the monoamine oxidase-A gene and with
      consequently high levels of brain monoamines and AVP in the SON, showed that free
      radicals are more abundant in their SON than in that of wild-type mice (WT).
      Antioxidant superoxide dismutase 1 and 2 and catalase enzyme activities were also
      higher in these mice than in WT. This may explain the observed absence of
      cytotoxicity that would otherwise be associated with such high level of free
      radicals. Treatment of Tg8 mice with alpha-MPT, a blocking agent for NA
      synthesis, decreased both the production of free radicals and the AVP levels in
      the SON. Furthermore, incubation of ex vivo slices including the SON with NA
      increased the production of free radicals and AVP levels in wild-type mice. When
      NA was associated with alpha-lipoic acid, an antioxidant blocking the production
      of free radicals, AVP remained at its control level, indicating that free
      radicals are required for the effect of NA on the expression of AVP. In slices
      incubated with SNP, a producer of NO, free radicals and AVP levels increased.
      When NA was associated with L-NAME (a NO synthase blocker), the levels of free
      radicals and AVP were the same as in controls. Thus, the noradrenaline-NO
      pathway, which stimulates the expression of vasopressin, involves free radicals.
      This study provides further evidence of the physiological importance of free
      radicals, which should no longer be considered solely as cytotoxic factors. 

PMID- 24681259
TI  - Compliance/adherence to physician-advised diagnostic and therapeutic strategies.

PMID- 24681258
TI  - Secondary prevention after ischemic stroke or transient ischemic attack.
AB  - BACKGROUND: Patients with stroke or transient ischemic attack are at increased
      risk of recurrent stroke. Transient ischemic attack is a harbinger for stroke
      merely hours to days after the initial transient ischemic attack. There is thus a
      narrow window of opportunity to initiate evidence-based therapies for secondary
      prevention of stroke. Our objective was to assess hospital adherence at discharge
      to secondary prevention measures after transient ischemic attack or ischemic
      stroke. METHODS: Observational study of patients in the Get With The Guidelines
      Stroke registry from 2007 to 2011. Patients were divided into 2 cohorts based on
      presentation: transient ischemic attack versus ischemic stroke. Adherence to
      evidence-based secondary prevention and other quality measures were assessed.
      RESULTS: Among the 858,835 patients with transient ischemic attack or ischemic
      stroke, 259,319 (30%) patients presented with a transient ischemic attack and
      599,516 (70%) patients presented with an ischemic stroke. After adjusting for
      patient and hospital characteristics, adherence to secondary prevention measures
      was consistently lower for the transient ischemic attack cohort (vs ischemic
      stroke cohort), who had lower odds of being discharged on antithrombotics (odds
      ratio [OR] 0.63; 95% confidence interval [CI], 0.59-0.66; P <.0001),
      anticoagulants for atrial fibrillation (OR 0.65; 95% CI, 0.61-0.68; P <.0001),
      lipid-lowering medication for LDL >100 mg/dL (OR 0.52; 95% CI, 0.50-0.54; P
      <.0001), intensive statin therapy (OR 0.74; 95% CI, 0.72-0.76; P <.0001), LDL
      cholesterol measurement (OR 0.66; 95% CI, 0.64-0.68; P <.0001), smoking cessation
      counseling (OR 0.83; 95% CI, 0.78-0.89; P <.0001), stroke education (OR 0.71; 95%
      CI, 0.69-0.73; P <.0001), or weight loss recommendations (OR 0.88; 95% CI, 0.85
      0.90; P <.0001). The adherence to evidence-based therapies increased
      significantly (P <.0001) over time (2007-2011) for both the cohorts, but the
      increasing trend was consistently lower for patients who presented with transient
      ischemic attack. CONCLUSIONS: In patients surviving an ischemic stroke or
      transient ischemic attack, adherence to evidence-based secondary prevention
      discharge measures were consistently less for patients with transient ischemic
      attack, thus representing a missed opportunity at instituting preventive measures
      to reduce the risk of recurrent stroke.

PMID- 24681256
TI  - Redox regulation of antioxidants, autophagy, and the response to stress:
      implications for electrophile therapeutics.
AB  - Redox networks in the cell integrate signaling pathways that control metabolism,
      energetics, cell survival, and death. The physiological second messengers that
      modulate these pathways include nitric oxide, hydrogen peroxide, and
      electrophiles. Electrophiles are produced in the cell via both enzymatic and
      nonenzymatic lipid peroxidation and are also relatively abundant constituents of
      the diet. These compounds bind covalently to families of cysteine-containing,
      redox-sensing proteins that constitute the electrophile-responsive proteome, the
      subproteomes of which are found in localized intracellular domains. These include
      those proteins controlling responses to oxidative stress in the cytosol-notably
      the Keap1-Nrf2 pathway, the autophagy-lysosomal pathway, and proteins in other
      compartments including mitochondria and endoplasmic reticulum. The signaling
      pathways through which electrophiles function have unique characteristics that
      could be exploited for novel therapeutic interventions; however, development of
      such therapeutic strategies has been challenging due to a lack of basic
      understanding of the mechanisms controlling this form of redox signaling. In this
      review, we discuss current knowledge of the basic mechanisms of thiol
      electrophile signaling and its potential impact on the translation of this
      important field of redox biology to the clinic. Emerging understanding of thiol
      electrophile interactions and redox signaling suggests replacement of the
      oxidative stress hypothesis with a new redox biology paradigm, which provides an
      exciting and influential framework for guiding translational research.

PMID- 24681260
TI  - The dynamics of shrinking and expanding drug-loaded microspheres: A semi
      empirical approach.
AB  - The dynamics of shrinking and expanding drug-loaded microspheres were studied
      using a diffusion equation in spherical coordinates. A movable boundary condition
      was incorporated as a convection term in the original model. The resulting
      convective-diffusive problem was solved using Laplace transform techniques with
      the Bromwich integral and the residue theorem. Analytical solutions were derived
      for the general case of shrinking or expanding microspheres and three particular
      kinetics expressions: linear growth, exponential swelling and exponential
      shrinking. Simulations show that microspheres with fast-swelling kinetics
      released their therapeutic cargo at a relatively slow rate in the first two
      cases. Ninety-nine percent of the medication was delivered at four times the
      effective time constant. In line with laboratory studies using bovine serum
      albumin, an increase in the shrinking rate led to a fast release of the
      medication from its carrier. The method was applied to analyze insulin transport
      through spherical Ca-alginate beads. A good agreement was noted between predicted
      and experimental data. The theoretical effective time constant was 114.0 min.

PMID- 24681262
TI  - Functional analysis of a highly conserved abundant larval transcript-2 (alt-2)
      intron 2 repeat region of lymphatic filarial parasites.
AB  - The filarial-specific protein abundant larval transcript-2 (ALT-2) is expressed
      exclusively in the infective larval stage (L3) and is a crucial protein for
      establishing immunopathogenesis in human hosts. The alt-2 gene has a conserved
      minisatellite repeat (29 or 27bp) in intron 2 (IR2) whose significance within
      lymphatic filarial species is unknown. Here, we report the role of IR2 in the
      regulation of alt-2 gene expression using an in vitro model. Using
      electrophoretic mobility shift assays, we identified the presence of a putative
      nuclear protein binding region within IR2. Subsequent transient expression
      experiments in eukaryotic cell lines demonstrated that the IR2 downregulated the
      expression of a downstream luciferase reporter gene, which was further validated
      with RT-PCR. We therefore identify IR2 as a suppressor element that regulates L3
      stage-specific expression of alt-2. 

PMID- 24681261
TI  - Towards a phylogenetic approach to the composition of species complexes in the
      North and Central American Triatoma, vectors of Chagas disease.
AB  - Phylogenetic relationships of insect vectors of parasitic diseases are important
      for understanding the evolution of epidemiologically relevant traits, and may be
      useful in vector control. The sub-family Triatominae (Hemiptera:Reduviidae)
      includes ~140 extant species arranged in five tribes comprised of 15 genera. The
      genus Triatoma is the most species-rich and contains important vectors of
      Trypanosoma cruzi, the causative agent of Chagas disease. Triatoma species were
      grouped into complexes originally by morphology and more recently with the
      addition of information from molecular phylogenetics (the four-complex
      hypothesis); however, without a strict adherence to monophyly. To date, the
      validity of proposed species complexes has not been tested by statistical tests
      of topology. The goal of this study was to clarify the systematics of 19 Triatoma
      species from North and Central America. We inferred their evolutionary
      relatedness using two independent data sets: the complete nuclear internal
      transcribed spacer-2 ribosomal DNA (ITS-2 rDNA) and head morphometrics. In
      addition, we used the Shimodaira-Hasegawa statistical test of topology to assess
      the fit of the data to a set of competing systematic hypotheses (topologies). An
      unconstrained topology inferred from the ITS-2 data was compared to topologies
      constrained based on the four-complex hypothesis or one inferred from our
      morphometry results. The unconstrained topology represents a statistically
      significant better fit of the molecular data than either the four-complex or the
      morphometric topology. We propose an update to the composition of species
      complexes in the North and Central American Triatoma, based on a phylogeny
      inferred from ITS-2 as a first step towards updating the phylogeny of the
      complexes based on monophyly and statistical tests of topologies. 

PMID- 24681263
TI  - Chikungunya virus adaptation to a mosquito vector correlates with only few point
      mutations in the viral envelope glycoprotein.
AB  - Like most arthropod-borne viruses (arboviruses), chikungunya virus (CHIKV) is a
      RNA virus maintained in nature in an alternating cycle of replication between
      invertebrate and vertebrate hosts. It has been assumed that host alternation
      restricts arbovirus genome evolution and imposes fitness trade-offs. Despite
      their slower rates of evolution, arboviruses still have the capacity to produce
      variants capable to exploit new environments. To test whether the evolution of
      the newly emerged epidemic variant of CHIKV (E1-226V) is constrained by host
      alternation, the virus was alternately-passaged in hamster-derived BHK-21 cells
      and Aedes aegypti-derived Aag-2 cells. It was also serially-passaged in BHK-21 or
      Aag-2 cells to promote adaptation to one cell type and presumably, fitness cost
      in the bypassed cell type. After 30 passages, obtained CHIKV strains were
      genetically and phenotypically characterized using in vitro and in vivo systems.
      Serially- and alternately-passaged strains can be distinguished by amino-acid
      substitutions in the E2 glycoprotein, responsible for receptor binding. Two
      substitutions at positions E2-64 and E2-208 only lower the dissemination of the
      variant E1-226V in Ae. aegypti. These amino-acid changes in the E2 glycoprotein
      might affect viral infectivity by altering the interaction between CHIKV E1-226V
      and the cellular receptor on the midgut epithelial cells in Ae. aegypti but not
      in Aedesalbopictus. 

PMID- 24681264
TI  - Progress on pursuit of human cytomegalovirus vaccines for prevention of
      congenital infection and disease.
AB  - Congenital infection of human cytomegalovirus (HCMV) is the leading cause of
      childhood hearing loss and mental retardation. Unfortunately, a preventive
      vaccine remains elusive. Two strategies have been employed to develop HCMV
      vaccines, including (1) attenuating HCMV to generate modified virus vaccines and
      (2) isolating subunit viral antigen(s) to create individual antigen vaccines. The
      most studied candidate in each category is live attenuated Towne virus and
      recombinant gB/MF59 vaccine, respectively. Although both were moderately
      efficacious, neither could induce the durable, robust humoral and cellular
      immunity commonly seen in HCMV seropositive subjects. In addition, both vaccines
      failed to induce neutralizing antibodies against viral infection of endothelial
      cells, epithelial cells and leukocytes. This review summarizes the recent
      understanding of host natural immunity to HCMV, including the importance of
      antibodies targeting HCMV epithelial tropism, and discusses its implications for
      vaccine design. We also highlight some recent key discoveries that may lead to
      the development of an effective HCMV vaccine. 

PMID- 24681265
TI  - Hybridization between previously isolated ancestors may explain the persistence
      of exactly two ancient lineages in the genome of the oyster parasite Perkinsus
      marinus.
AB  - Theory predicts that neutral genetic variation accumulates within populations to
      a level determined by gains through mutation and losses by genetic drift. This
      balance results in a characteristic distribution of allelic variation with the
      maximum allelic difference determined by effective population size. Here, we
      report a striking departure from these expectations in the form of allelic
      dimorphism, observed at the majority of seven loci examined in Perkinsus marinus,
      an important oyster parasite that causes Dermo disease. DNA sequences were
      collected from five loci flanking microsatellite repeats and two loci coding for
      superoxide dismutase enzymes that may mediate the parasite's interaction with its
      host. Based on 474 sequences, sampled across 5000 km of the eastern United States
      coastline, no more than two alleles were observed at each locus (discounting
      singletons). Depending on the locus, the common allele ranged in overall
      frequency from 72% to 92%. At each locus the two alleles differed substantially
      (3.8% sequence difference, on average), and the among-locus variance in
      divergences was not sufficient to reject a simultaneous origin for all
      dimorphisms using approximate Bayesian methods. Dimorphic alleles were estimated
      to have diverged from a common ancestral allele at least 0.9 million years ago.
      Across these seven loci, only five other alleles were ever observed, always as
      singletons and differing from the dimorphic alleles by no more than two
      nucleotides. Free recombination could potentially have shuffled these dimorphisms
      into as many as 243 multilocus combinations, but the existence of only ten
      combinations among all samples strongly supports low recombination frequencies
      and is consistent with the observed absence of intragenic recombination. We
      consider several demographic and evolutionary hypotheses to explain these
      patterns. Few can be conclusively rejected with the present data, but we advance
      a recent hybridization of ancient divergent lineages scenario as the most
      parsimonious.

PMID- 24681266
TI  - Isolation and characterization of a Neisseria strain from the liver of a Chinese
      Peking duck.
AB  - A Neisseria strain, Neisseria sp. AH-N10, was isolated from liver of a Chinese
      Peking duck and characterized using a number of phenotypic and genotypic
      approaches. Based on scanning electron microscopy examination, the isolated
      strain has the typical structure of Neisseria species. Sequence comparison of 16S
      rRNA gene and phylogenetic analysis suggest that Neisseria sp. AH-N10 is closely
      related to Neisseria canis, which was previously isolated from a human dog bite
      wound. Animal infection experiments demonstrated that the isolated Neisseria sp.
      AH-N10 is pathogenic in ducks and mice. The pathogenicity to humans and
      evolutional origin of this Neisseria strain should be further investigated. 

PMID- 24681268
TI  - Stromal interaction molecules as important therapeutic targets in diseases with
      dysregulated calcium flux.
AB  - Calcium ions have important roles in cellular processes including intracellular
      signaling, protein folding, enzyme activation and initiation of programmed cell
      death. Cells maintain low levels of calcium in their cytosol in order to regulate
      these processes. When activation of calcium-dependent processes is needed, cells
      can release calcium stored in the endoplasmic reticulum (ER) into the cytosol to
      initiate the processes. This can also initiate activation of plasma membrane
      channels that allow entry of additional calcium from the extracellular milieu.
      The change in calcium levels is referred to as calcium flux. A key protein
      involved in initiation of calcium flux is Stromal Interaction Molecule 1 (STIM1),
      which has recently been identified as a sensor of ER calcium levels. STIM1 is an
      ER transmembrane protein that is activated by a drop in ER calcium levels. Upon
      activation, STIM1 interacts with a plasma membrane protein, ORAI1, to activate
      ORAI-containing calcium-selective plasma membrane channels. Dysregulation of
      calcium flux has been reported in cancers, autoimmune diseases and other
      diseases. STIM1 is a promising target in drug discovery due to its key role early
      in calcium flux. Here we review the involvement and importance of STIM1 in
      diseases and why STIM1 is a viable target for drug discovery. This article is
      part of a Special Issue entitled: Calcium signaling in health and disease. Guest
      Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and
      Marc Moreau. 

PMID- 24681269
TI  - RE: Non-specific effects of co-administration of live measles, yellow fever and
      pentavalent vaccines on mortality?

PMID- 24681267
TI  - Systematic detection of internal symmetry in proteins using CE-Symm.
AB  - Symmetry is an important feature of protein tertiary and quaternary structures
      that has been associated with protein folding, function, evolution, and
      stability. Its emergence and ensuing prevalence has been attributed to gene
      duplications, fusion events, and subsequent evolutionary drift in sequence. This
      process maintains structural similarity and is further supported by this study.
      To further investigate the question of how internal symmetry evolved, how
      symmetry and function are related, and the overall frequency of internal
      symmetry, we developed an algorithm, CE-Symm, to detect pseudo-symmetry within
      the tertiary structure of protein chains. Using a large manually curated
      benchmark of 1007 protein domains, we show that CE-Symm performs significantly
      better than previous approaches. We use CE-Symm to build a census of symmetry
      among domain superfamilies in SCOP and note that 18% of all superfamilies are
      pseudo-symmetric. Our results indicate that more domains are pseudo-symmetric
      than previously estimated. We establish a number of recurring types of symmetry
      function relationships and describe several characteristic cases in detail. With
      the use of the Enzyme Commission classification, symmetry was found to be
      enriched in some enzyme classes but depleted in others. CE-Symm thus provides a
      methodology for a more complete and detailed study of the role of symmetry in
      tertiary protein structure [availability: CE-Symm can be run from the Web at
      http://source.rcsb.org/jfatcatserver/symmetry.jsp. Source code and software
      binaries are also available under the GNU Lesser General Public License (version
      2.1) at https://github.com/rcsb/symmetry. An interactive census of domains
      identified as symmetric by CE-Symm is available from
      http://source.rcsb.org/jfatcatserver/scopResults.jsp]. 

PMID- 24681270
TI  - Impact of a mixed bacterial lysate (OM-85 BV) on the immunogenicity, safety and
      tolerability of inactivated influenza vaccine in children with recurrent
      respiratory tract infection.
AB  - It is known that the immunogenicity and efficacy of conventional inactivated
      influenza vaccines (IIVs) are not completely satisfactory in children. The aim of
      this prospective, randomised, single-blind study was to compare the immune
      response to, and the effectiveness and safety of, an IIV (Fluarix,
      GlaxoSmithKline Biologicals, Rixensart, Belgium) administered to 68 children aged
      36-59 months affected by recurrent respiratory tract infections (RRTIs) who were
      vaccinated with (n=33) or without (n=35) the mixed bacterial lysate OM-85 BV
      (Broncho-vaxom, Vifor Pharma, Geneva, Switzerland). OM-85 BV had no effect on
      seroconversion or seroprotection rates, geometric mean titres, or dendritic
      cells, which were not significantly different between the two groups. Moreover,
      OM-85 BV did not significantly increase the pool of the memory B cells that
      produce IgG and IgM antibodies against the influenza antigens. However,
      respiratory morbidity was significantly lower in the children treated with OM-85
      BV (p<0.05), thus confirming its positive effect on the incidence of RRTIs. There
      was no difference in the incidence of adverse events between the two groups.
      These findings show that the immune response of children to influenza vaccine is
      not significantly influenced by the administration of OM-85 BV. However, the use
      of OM-85 before and at the same time as IIV seems to reduce respiratory
      morbidity, and seems to be safe and well tolerated. 

PMID- 24681271
TI  - Combination of MIDGE-Th1 DNA vaccines with the cationic lipid SAINT-18: studies
      on formulation, biodistribution and vector clearance.
AB  - We have previously shown that the combination of MIDGE-Th1 DNA vectors with the
      cationic lipid SAINT-18 increases the immune response to the encoded antigen in
      mice. Here, we report on experiments to further optimize and characterize this
      approach. We evaluated different formulations of MIDGE-Th1 vectors with SAINT-18
      by assessing their influence on the transfection efficiency in cell culture and
      on the immune response in mice. We found that high amounts of SAINT-18 in
      formulations with a w/w ratio MIDGE Th1/SAINT-18 of 1:4.8 are beneficial for cell
      transfection in vitro. In contrast, the formulation of HBsAg-encoding MIDGE-Th1
      DNA vectors with the lowest amount of SAINT-18 (w/w ratio MIDGE Th1/SAINT-18 of
      1:0.5) resulted in the highest serum IgG1 and IgG2a levels after intradermal
      immunization of mice. Consequently, latter formulation was selected for a
      comparative biodistribution study in rats. Following intradermal administration
      of both naked and formulated MIDGE-Th1 DNA, the vectors localized primarily at
      the site of injection. Vector DNA levels decreased substantially over the two
      months duration of the study. When administered in combination with SAINT-18, the
      vectors were found in significantly higher amounts in draining lymph nodes in
      comparison to administration of naked MIDGE-Th1 DNA. We propose that the high
      immune responses induced by MIDGE-Th1/SAINT-18 lipoplexes are mediated by
      enhanced transfection of cells in vivo, resulting in stronger antigen expression
      and presentation. Importantly, the combination of MIDGE-Th1 vectors with SAINT-18
      was well tolerated in mice and rats and is expected to be safe in human clinical
      applications. 

PMID- 24681272
TI  - Role of viral RNA and lipid in the adverse events associated with the 2010
      Southern Hemisphere trivalent influenza vaccine.
AB  - In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there
      was an unexpected increase in post-marketing adverse event reports of febrile
      seizures (FS) in children under 5 years of age shortly after vaccination with the
      CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous
      CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described
      the contribution to these adverse events of the 2010 SH influenza strains as
      expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from
      whole blood cells and induction of NF-kappaB activation in HEK293 reporter cells.
      The aim of the present study was to identify the root cause components that
      elicited the elevated cytokine/chemokine and NF-kappaB signature. Our studies
      demonstrated that the pyrogenic signal was associated with a heat-labile, viral
      derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral
      lipid-mediated delivery of short, fragmented viral RNA was the key trigger for
      the increased cytokine/chemokine secretion and NF-kappaB activation. It is likely
      that the FS reported in children <5 years were due to a combination of the new
      influenza strains included in the 2010 SH TIV and the CSL standard method of
      manufacture preserving strain-specific viral components of the new influenza
      strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1
      A/California/07/2009). These combined to heighten immune activation of innate
      immune cells, which in a small proportion of children <5 years of age is
      associated with the occurrence of FS. The data also demonstrates that CSL TIVs
      formulated with increased levels of splitting agent (TDOC) for the
      B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro,
      identifying a potential path forward for generating a CSL TIV indicated for use
      in children <5 years. 

PMID- 24681273
TI  - Systematic evaluation of in vitro and in vivo adventitious virus assays for the
      detection of viral contamination of cell banks and biological products.
AB  - Viral vaccines and the cell substrates used to manufacture them are subjected to
      tests for adventitious agents, including viruses, contaminate. Some of the
      compendial methods (in vivo and in vitro in cell culture) were established in the
      mid-20th century. These methods have not been subjected to current assay
      validation, as new methods would need to be. This study was undertaken to provide
      insight into the breadth (selectivity) and sensitivity (limit of detection) of
      the routine methods, two such validation parameters. Sixteen viral stocks were
      prepared and characterized. These stocks were tested in serial dilutions by the
      routine methods to establish which viruses were detected by which methods and
      above what limit of detection. Sixteen out of sixteen viruses were detected in
      vitro, though one (bovine viral diarrhea virus) required special conditions to
      detect and another (rubella virus) was detected with low sensitivity. Many were
      detected at levels below 1 TCID50 or PFU (titers were established on the
      production cell line in most cases). In contrast, in vivo, only 6/11 viruses were
      detected, and 4 of these were detected only at amounts one or more logs above 1
      TCID50 or PFU. Only influenza virus and vesicular stomatitis virus were detected
      at lower amounts in vivo than in vitro. Given the call to reduce, refine, or
      replace (3Rs) the use of animals in product safety testing and the emergence of
      new technologies for the detection of viruses, a re-examination of the current
      adventitious virus testing strategies seems warranted. Suggested pathways forward
      are offered. 

PMID- 24681274
TI  - Ready or not? School preparedness for California's new personal beliefs exemption
      law.
AB  - OBJECTIVE: This paper describes elementary school officials' awareness of and
      preparedness for the implementation of California's new exemption law that went
      into effect on January 1, 2014. The new law prescribes stricter requirements for
      claiming a personal beliefs exemption from mandated school-entry immunizations.
      METHOD: We used cross-sectional data collected from a stratified random sample of
      315 schools with low, middle, and high rates of personal beliefs exemptions. We
      described schools' awareness and specific knowledge of the new legislation and
      tested for differences across school types. We additionally tested for
      associations between outcome variables and school and respondent characteristics
      using ordered logit and negative binomial regression. Finally, we described
      schools' plans and needs for implementing the new legislation. RESULTS:
      Elementary school staff reported an overall low level of awareness and knowledge
      about the new legislation and could identify few of its features. We observed,
      however, that across the exemption-level strata, respondents from high-PBE
      schools reported significantly higher awareness, knowledge and feature
      identification compared to respondents from low-PBE schools. Multivariate
      analyses revealed only one significant association with awareness, knowledge and
      identification: respondent role. Support staff roles were associated with lower
      odds of having high self-rated awareness or knowledge compared to health workers,
      as well as with a reduced log count of features identified. Though most school
      officials were able to identify a communication plan, schools were still in need
      of resources and support for successful implementation, in particular, the need
      for information on the new law. CONCLUSION: Schools need additional information
      and support from state and local agencies in order to successfully implement and
      enforce California's new school immunization law. In particular, our results
      suggest the need to ensure information on the new law reaches all levels of
      school staff.

PMID- 24681275
TI  - Antitoxins for diphtheria and tetanus decline more slowly after vaccination with
      DTwP than with DTaP: a study in a Chinese population.
AB  - OBJECTIVES: DTP vaccines are used for the prevention of pertussis, diphtheria and
      tetanus. In 2007, in Gaobeidian city, China, the DTwP vaccine was replaced with
      DTaP. This study described the diphtheria and tetanus sero-epidemiology in
      subjects vaccinated solely with DTwP or DTaP. METHODS: Blood samples were
      obtained between October 2012 and June 2013 from 587 healthy subjects aged 2-17
      years. Serum IgG antibodies against diphtheria and tetanus were determined using
      ELISA. Interrupted time series analyses examined the changes in antitoxin levels
      over time and analyzed the alterations in diphtheria and tetanus antitoxin levels
      after the vaccine switch. RESULTS: Mean concentrations of diphtheria antitoxin
      and tetanus antitoxin were 0.074 IU/ml (95% CI 0.065-0.084) and 0.063 IU/ml (95%
      CI 0.053-0.076). The protection rates (antitoxins >0.01 IU/ml) for diphtheria and
      tetanus were 88.25% and 82.11%. Mean antitoxin levels for both diphtheria and
      tetanus decreased with increasing age, but this decrease was much slower for DTwP
      than DTaP. CONCLUSIONS: Although the observed protection rates for diphtheria and
      tetanus were sufficient to prevent an outbreak at present, the means levels of
      diphtheria and tetanus antitoxins decreased with increasing age; therefore,
      booster vaccinations at 7 and 12 years of age would be strengthened in Gaobeidian
      city, China.

PMID- 24681276
TI  - The role of mesopores in MTBE removal with granular activated carbon.
AB  - This activated carbon research appraised how pore size and empty-bed contact time
      influenced the removal of methyl tert-butyl ether (MTBE) at part-per-billion
      (ppb) concentrations when MTBE was the sole organic impurity. The study compared
      six granular activated carbons (GACs) from three parent sources; these GACs
      contained a range of pore volume distributions and had uniform slurry pHs of 9.7
      10.4 (i.e. the carbons' bulk surface chemistries were basic). Several of these
      activated carbons had been specifically tailored for enhanced sorption of trace
      organic compounds. In these tests, MTBE was spiked into deionized-distilled water
      (~pH 7); MTBE loading was measured by isotherms and by rapid small-scale column
      tests (RSSCTs) that simulated full-scale empty-bed contact times of 7, 14, and 28
      min. The results showed that both ultra-fine micropores and small-diameter
      mesopores were important for MTBE adsorption. Specifically, full MTBE loading
      during RSSCTs bore a strong correlation (R(2) = 0.94) to the product (mL/g *
      mL/g) of pore volume <=4.06 A wide and pore volume between ~22 A and ~59 A wide.
      This correlation was greater than for the product of any other pore volume
      combinations. Also, this product exhibited a stronger correlation than for just
      one or the other of these two pore ranges. This multiplicative relationship
      implied that both of these pore sizes were important for the optimum GAC
      performance of these six carbons (i.e. favorable mass transfer coupled with
      favorable sorption). The authors also compared MTBE mass loading during RSSCTs
      (MUg MTBE/g GAC) to isotherm capacity (MUg MTBE/g GAC). This RSSCT loading
      "efficiency" ranged from 28% to 96% for the six GACs; this efficiency correlated
      most strongly to pores that were 14-200 A wide (R(2) = 0.94). This correlation
      indicated that only those carbons with a sufficient volume of 14-200 A pores
      could adsorb MTBE to the extent that would be predicted from isotherm data. 

PMID- 24681277
TI  - Exploitation of rolling circle amplification for the construction of large phage
      display antibody libraries.
AB  - Phage display antibody libraries have proven to have a significant role in the
      discovery of therapeutic antibodies and polypeptides with desired biological and
      physicochemical properties. Obtaining a large and diverse phage display antibody
      library, however, is always a challenging task. Various steps of this technique
      can still undergo optimization in order to obtain an efficient library. In the
      construction of a single chain fragment variable (scFv) phage display library,
      the cloning of the scFv fragments into a phagemid vector is of crucial
      importance. An efficient restriction enzyme digestion of the scFv DNA leads to
      its proper ligation with the phagemid followed by its successful cloning and
      expression. Here, we are reporting a different approach to enhance the efficiency
      of the restriction enzyme digestion step. We have exploited rolling circle
      amplification (RCA) to produce a long strand of DNA with tandem repeats of scFv
      sequences, which is found to be highly susceptible to restriction digestion. With
      this important modification, we are able to construct a large phage display
      antibody library of naive SJL/J mice. The size of the library is estimated as
      ~10(8) clones. The number of clones containing a scFv fragment is estimated at
      90%. Hence, the present results could considerably aid the utilization of the
      phage-display technique in order to get an efficiently large antibody library. 

PMID- 24681278
TI  - Comparison of vehicles to collect dentinal fluid for molecular analysis.
AB  - OBJECTIVES: To test the hypothesis that a material with higher water absorption
      than polyvinylidene fluoride (PVDF) could increase the yield of target molecules
      from exposed dentine. METHODS: In a series of standard tests, different cellulose
      membranes were compared to a PVDF counterpart for their ability to absorb water
      and release protein. In a subsequent randomized clinical trial, the cellulose
      material with the most favourable values was compared to PVDF regarding the
      levels of MMP-2 that could be collected from exposed dentine of healthy human
      teeth during filling replacement. MMP-2 levels were determined by enzyme-linked
      immunosorbent assay (ELISA). Data from the laboratory experiments were compared
      between materials using the appropriate parametric tests. The frequency of cases
      yielding quantifiable levels of MMP-2 was compared between materials by Fisher's
      exact test. The level of significance was set at 5%. RESULTS: The cellulose
      membrane with the largest pore size (12-15MUm) absorbed significantly (P<0.05)
      more water than PVDF. It showed a protein release that was similar to that of
      PVDF, while the cellulose membranes with smaller pore size retained significantly
      more protein (P<0.05). Using the large-pore cellulose membrane, MMP-2 could be
      collected at a quantifiable level from the dentine of healthy teeth in 9 of 13
      cases, compared to 1 of 13 with the PVDF membrane (P<0.05). CONCLUSIONS: Under
      the current conditions, a large-pore cellulose membrane yielded more of a
      molecule of diagnostic value compared to a standard PVDF membrane. CLINICAL
      SIGNIFICANCE: Molecular diagnostics of dentinal fluid are hampered by low yields.
      In the current study, it was shown that cellulose membranes are more useful to
      collect MMP-2 from dentinal fluid than PVDF membranes.

PMID- 24681279
TI  - Stereotactic Ablative Radiotherapy for stage I histologically proven non-small
      cell lung cancer: an Italian multicenter observational study.
AB  - OBJECTIVES: Aim of this retrospective multicenter observational study was to
      provide data on outcomes and prognostic factors in patients affected with stage I
      histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy
      (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials.
      MATERIALS AND METHODS: We analyzed a cohort of 196 patients with
      histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years
      old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty
      five patients had stage IA disease (79.1%) and 41 patients stage IB disease
      (20.9%). Total doses ranged from 48 to 60 Gy in 3-8 fractions. Primary endpoints
      of the study were safety (acute and late toxicity) and efficacy (Local Control,
      Disease-Free Survival, Overall and Cancer-Specific Survival). RESULTS: Median
      follow-up time was 30 months. The percentage of grade >=2 pulmonary toxicity was
      3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival
      was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local
      and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years
      of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68%
      and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months,
      while median overall survival time was 54 months. At multivariate analysis, stage
      IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p
      = 0.006; HR 2.38, p = 0.009; HR 4.06, p <= 0.001, respectively). A difference in
      survival according to stage was also evident at the log-rank test (p <= 0.0001
      for CSS and OS). CONCLUSION: The results of the present study support the routine
      use of SABR for stage I NSCLC in a daily practice environment. The only
      prognostic factor that has been confirmed by our analysis was tumor stage (IA vs.
      IB).

PMID- 24681280
TI  - Endobronchial metastasis: an epidemiologic and clinicopathologic study of 174
      consecutive cases.
AB  - PURPOSE: Endobronchial metastases from extrapulmonary solid tumors are a rare
      event and currently available epidemiological and clinico-pathological data
      mainly derive from anecdotal case reports. METHODS: A series of 174 consecutive
      cases of endobronchial metastases from extrathoracic solid tumors were collected
      over a period of 18 years. Immunohistochemistry was performed in 115 cases.
      Complete imaging features were available in 81 patients, and analysis of the
      latency period between primitive tumor diagnosis and occurrence of endobronchial
      metastasis was obtained. RESULTS: Among all bronchoscopic examinations performed
      in the same period for malignancy, a mean of 5.6 cases per year consisted of
      endobronchial metastases (range 2-17 cases), with a statistically significant
      increase when comparing the periods 1992-2000 (65 cases, 37%) and 2001-2009 (109
      cases, 63%) (p = 0.05). Overall, 4% of endobronchial biopsies for suspected
      malignancy disclosed an endobronchial metastasis from extrapulmonary tumor.
      Breast (52 cases, 30%), colorectal (42 cases, 24%), renal (14%), gastric (6%) and
      prostate (4.5%) cancers and melanoma (4.5%) were the most common metastatic
      neoplasms presenting as endobronchial mass. One-hundred fifty-four cases were
      identified after the primitive tumor diagnosis (metachronous cases, 89%), 11
      cases were simultaneously evidenced in extrapulmonary and endobronchial sites
      (synchronous cases, 6%), while 9 occult metastatic cases (5%) first presented as
      endobronchial mass (anachronous cases). Overall, mean latency from extrapulmonary
      tumor diagnosis and endobronchial metastasis was 136 months (range, 1-300
      months). The most frequent symptoms were dyspnea (23%), cough (15%) and
      haemoptysis (12%), while 26% of patients were totally asymptomatic. At radiology,
      53% presented as multiple pulmonary nodules, while other cases presented as hilar
      and mediastinal mass, single peripheral nodule, atelectasis or pleural effusion.
      CONCLUSIONS: Endobronchial metastases from extrapulmonary tumors account for
      about 4% of all bronchoscopic biopsies performed for suspected malignancy and in
      5% of the cases the metastasis is the first manifestation of the neoplasm.

PMID- 24681281
TI  - Computed tomography attenuation predicts the growth of pure ground-glass nodules.
AB  - OBJECTIVES: Cases of lung cancer with pure ground-glass nodules (GGNs) have been
      detected with increasing frequency since the advent of computed tomography (CT),
      and growth is sometimes noted during follow-up. The objective of this study was
      to evaluate the potential predictive factors for pure GGN growth. MATERIALS AND
      METHODS: We retrospectively examined 124 cases involving pure GGNs. Patients were
      monitored for > 2 years using high-resolution CT. After a median follow-up period
      of 57.0 months, GGNs showed growth in 64 of the 124 cases. We compared the
      patient characteristics and tumor properties of cases with and without growth.
      The predictive value of the mean CT attenuation for GGN growth was evaluated
      using receiver operating characteristic curve analysis. RESULTS: Univariate
      analysis revealed significant differences between mean CT attenuation values in
      patients with and without growth (-602.9 +/- 90.7 Hounsfield units [HU] vs -705.7
      +/- 77.7HU, P < 0.0001). The final incidence of growth was estimated to be
      significantly higher for lesions with a mean CT attenuation value of >= -670HU (n
      = 62; 93.2%) than for lesions with values of < -670HU (n = 62; 31.6%; P <
      0.0001). The sensitivity and specificity for predicting tumor growth using this
      cutoff value were 78.1% and 80.0%, respectively (area under the curve, 0.81).
      CONCLUSION: The mean CT attenuation value could be useful in predicting the
      growth of GGNs.

PMID- 24681282
TI  - Understanding PTSD comorbidity and suicidal behavior: associations among
      histories of alcohol dependence, major depressive disorder, and suicidal ideation
      and attempts.
AB  - Individuals with posttraumatic stress disorder (PTSD) are at an elevated risk for
      experiencing suicidal thoughts and actions. However, a relative dearth of
      research has examined factors that may impact this relation, such as common co
      occurring disorders. Utilizing the National Comorbidity Survey-Replication data,
      the current study examined comparisons between comorbid PTSD and major depressive
      disorder (MDD) and comorbid PTSD and alcohol dependence (AD) in relation to
      suicidal ideation and suicide attempts. It was hypothesized that comorbid MDD
      would be associated with an elevated likelihood of suicidal ideation, while
      comorbid AD would be associated with an elevated likelihood of suicide attempt
      history. Results indicated that only PTSD-AD was significantly associated with an
      elevated likelihood of endorsing histories of both suicidal ideation and suicide
      attempts. These findings suggest that AD may be a critical risk factor for
      acquiring the capability for suicide attempts.

PMID- 24681283
TI  - The in vitro maintenance of clock genes expression within the rat pineal gland
      under standard and norepinephrine-synchronized stimulation.
AB  - Although the norepinephrine (NE) synchronization protocol was proved to be an
      important procedure for further modulating in vitro pineal melatonin synthesis,
      the maintenance of clock genes under the same conditions remained to be
      investigated. The aim of this study was to investigate the maintenance of the
      clock genes expression in pineal gland cultures under standard and NE
      synchronized stimulation. The glands were separated into three experimental
      groups: Control, Standard (acute NE-stimulation), and NE-synchronized. The
      expression of Bmal1, Per2, Cry2, Rev-erbalpha, the clock controlled gene Dbp and
      Arylalkylamine-N-acetyltransferase were investigated, as well as melatonin
      content. No oscillations were observed in the expression of the investigated
      genes from the control group. Under Standard NE stimulation, the clock genes did
      not exhibit a rhythmic pattern of expression. However, in the NE-synchronized
      condition, a rhythmic expression pattern was observed in all cases. An
      enhancement in pineal gland responsiveness to NE stimulation, reflected in an
      advanced synthesis of melatonin was also observed. Our results reinforce our
      previous hypothesis that NE synchronization of pineal gland culture mimics the
      natural rhythmic release of NE in the gland, increasing melatonin synthesis and
      keeping the pineal circadian clock synchronized, ensuring the fine adjustments
      that are relied in the clockwork machinery. 

PMID- 24681284
TI  - Ivermectin reduces sexual behavior in female rats.
AB  - Ivermectin (IVM) is an antiparasitic drug that is widely used in domestic
      animals. In mammals, IVM acts as a gamma-aminobutyric acid (GABA) receptor
      agonist. This neurotransmitter plays an important role in the regulation of
      female sexual behavior. The present study investigated the effects of therapeutic
      (0.2 mg/kg) and high (1.0 mg/kg) IVM doses on female sexual behavior in
      physiological and pharmacological conditions. Female rats in estrus or treated
      with estradiol valerate to induce sexual behavior 24 h before the experiments
      were used. Ivermectin was administered 15 min before the sexual observations. The
      number of lordosis events in 10 mounts was recorded to calculate the lordosis
      quotient. The intensity of lordosis (0 [no lordosis], 1 [low lordosis], 2 [normal
      lordosis] and 3 [exaggerated lordosis]) was scored. In estrus and hormonal
      treated female rats, both IVM doses decreased the intensity of the lordosis
      reflex and the percentage of females that presented high levels of lordosis
      (exaggerated lordosis). However, the number of females that presented lordosis
      was unaltered. We conclude that in both hormonal conditions, 0.2mg/kg IVM
      treatment reduced female sexual behavior and the execution of the lordosis
      reflex. The present results may be useful for avoiding the side effects of this
      drug in veterinary practice.

PMID- 24681285
TI  - Neurotoxicity from prenatal and postnatal exposure to methylmercury.
AB  - The extent to which postnatal methylmercury exposure contributes to
      neurobehavioral delays is uncertain. Confounding may occur because the child's
      dietary exposure likely correlates with the mother's. This conundrum was examined
      in the Faroese birth cohort 1 born in 1986-1987. Exposure parameters included
      mercury concentrations in maternal hair at parturition, cord blood, and child
      blood and hair at the age-7 clinical examination (N=923). In regression analyses,
      the child's current blood-mercury at age 7 (N=694) showed only weak associations
      with the neuropsychological test variables, but visuospatial memory revealed a
      significant negative association. Mutual adjustment caused decreases of the
      apparent effect of the prenatal exposure. However, such adjustment may lead to
      underestimations due to the presence of correlated, error-prone exposure
      variables. In structural equation models, all methylmercury exposure parameters
      were instead entered into a latent exposure variable that reflected the total
      methylmercury load. This latent exposure showed significant associations with
      neurodevelopmental deficits, with prenatal exposure providing the main
      information. However, postnatal methylmercury exposure appeared to contribute to
      neurotoxic effects, in particular in regard to visuospatial processing and
      memory. Thus, addition in the regression analysis of exposure information
      obtained at a different point in time was not informative and should be avoided.
      Further studies with better information on exposure profiles are needed to
      characterize the effects of postnatal methylmercury exposure. 

PMID- 24681286
TI  - Fetal lung maturity testing.

PMID- 24681287
TI  - Impact of 17-alpha-hydroxyprogesterone caproate on cytochrome P450s in primary
      cultures of human hepatocytes.
AB  - OBJECTIVE: The aim of this study was to examine the effects of 17-alpha
      hydroxyprogesterone caproate (17OHP-C) on the activity and expression of several
      common hepatic cytochrome P450 (CYP) enzymes. STUDY DESIGN: Primary human
      hepatocytes were pretreated with vehicle or 17OHP-C (0.1 and 1 MUmol/L) for 72
      hours, then incubated for 1 hour with a cocktail of CYP substrates. The activity
      of various CYP enzymes was determined by measuring the formation of the
      metabolites of specific CYP substrates, using liquid chromatography-tandem mass
      spectrometry. The messenger RNA expression of various CYP enzymes was determined
      by real-time polymerase chain reaction. RESULTS: In primary cultures of human
      hepatocytes, 17OHP-C minimally altered the activity or messenger RNA levels of
      CYP1A2, CYP2C9, CYP2D6, and CYP3A. However, 17OHP-C at 1 MUmol/L increased
      CYP2C19 activity by 2.8-fold (P < .01) and CYP2C19 expression by 2.4-fold (P <
      .001), compared with vehicle-treated cells. A strong positive correlation between
      activity and expression of CYP2C19 was also observed (r = 0.9, P < .001).
      CONCLUSION: The activity and expression of hepatic CYP2C19 was significantly
      increased by 17OHP-C in primary cultures of human hepatocytes. This suggests that
      exposure to medications that are metabolized by CYP2C19 may be decreased in
      pregnant patients receiving 17OHP-C. Metabolism of substrates of CYP1A2, CYP2C9,
      CYP2D6, and CYP3A are not expected to be altered in patients receiving 17OHP-C.

PMID- 24681288
TI  - Vaginal dilation treatment in women with vaginal hypoplasia: a prospective one
      year follow-up study.
AB  - OBJECTIVE: Vaginal dilation treatment has been shown to be a (cost) effective
      first-line alternative to surgery in normalizing vaginal length and improving
      sexual function in women with vaginal hypoplasia. There remains, however, a need
      for prospective studies, with long-term assessment of multiple outcomes. STUDY
      DESIGN: This was a prospective, single-centre observational study of 16 women
      with Mayer-Rokitansky-Kuster-Hauser syndrome (n = 12) or 46,XY disorders of sex
      development (n = 4). All women underwent an outpatient vaginal dilation program
      supervised by a psychologist and physiotherapist. At baseline (T0), stop of
      treatment (T1) and 1 year follow-up (T2), semistructured interviews, and
      validated questionnaires assessed sexual function and distress, self-esteem,
      vaginal perceptions, and health-related quality of life. Gynecological
      examinations evaluated vaginal dimensions. RESULTS: Ten women completed the
      program, 3 are still in the program, and dilation failed in 3 and chose
      vaginoplasty. Sixty-nine percent reached a normal vaginal length (>=6.5 cm) in
      5.8 +/- 3.3 months. Seventy percent were sexually active with pleasurable
      experiences at T1, 57% at T2. The significant decrease in sexual distress at T1
      (P < .05) was followed by a nonsignificant increase at T2. Depressive mood
      symptomatology remained high at T1 and T2, related to loss of bodily integrity
      and fertility. The majority refused further psychological counseling. CONCLUSION:
      Vaginal dilation treatment should remain the cornerstone of treatment in women
      with vaginal hypoplasia. However, the diagnosis remains to have a negative impact
      on emotional well-being in the long term. The role of psychological intervention
      as both a primary and adjuvant treatment needs clear evaluation.

PMID- 24681289
TI  - Case-control analysis of maternal prenatal analgesic use and cardiovascular
      malformations: Baltimore-Washington Infant Study.
AB  - OBJECTIVE: We sought to assess maternal prenatal use of analgesics and risk of
      cardiovascular malformations (CVM) in the offspring. STUDY DESIGN: Data from the
      Baltimore-Washington Infant Study, a population-based case-control investigation
      of CVM, were used to examine selected isolated CVM diagnoses and maternal
      analgesic use during the periconceptional period (3 months before and after
      conception). We compared case and control infants on frequency of maternal use of
      analgesics and estimated adjusted odds ratios (adjORs) and 95% confidence
      intervals (CI) with logistic regression models for specific CVM phenotypes.
      RESULTS: Frequency of periconceptional use of any analgesic was 52% among control
      mothers and 53% among case mothers. Analyses by CVM diagnoses identified an
      association of tetralogy of Fallot with maternal acetaminophen use (adjOR, 1.6;
      95% CI, 1.1-2.3) and dextrotransposition of the great arteries with intact
      ventricular septum with maternal nonsteroidal antiinflammatory drug use (adjOR,
      3.2; 95% CI, 1.2-8.7). CONCLUSION: Analgesic use during the periconceptional
      period was not associated with CVM in the aggregate or with most phenotypes of
      CVM examined. Associations with 2 phenotypes of CVM may have occurred by chance.
      These findings warrant corroboration and further study, including further
      evaluation of the observed associations, the dose of analgesic taken, more
      specific timing of analgesic use, and indications for use.

PMID- 24681290
TI  - Predictors of 2-year cognitive performance after laser surgery for twin-twin
      transfusion syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine risk factors for poor
      cognitive performance among children who are treated with in utero selective
      laser photocoagulation of communicating vessels for twin-twin transfusion
      syndrome. STUDY DESIGN: This was a prospectively enrolled cohort study. Cognitive
      performance at age 2 years (+/-6 weeks) was assessed with the Battelle
      Developmental Inventory 2nd Edition (BDI-2). Multilevel regression models
      evaluated risk factors for poor cognitive performance at shared (pregnancy) and
      individual (child) levels. In addition to development, blindness, deafness, and
      cerebral palsy were assessed based on physical examination. A priori power
      analysis determined that a sample of >=100 children was required for adequate
      statistical power (0.80). RESULTS: One hundred children (57 families) were
      evaluated. Total BDI-2 score was within normal range (mean, 101.3 +/- [SD]12.2);
      1 child had a BDI-2 score of <70. Individual child-level risk factors for lower
      BDI-2 included male sex (beta = -0.37; P < .01), lower head circumference (beta =
      0.28; P < .01), and higher diastolic blood pressure (beta = -0.29; P < .01). At
      the pregnancy level, lower maternal education (beta = 0.60; P < .001), higher
      Quintero stage (beta = -0.36; P < .01), and lower gestational age at birth (beta
      = 0.30; P < .01) were associated with worse cognitive outcomes. Donor/recipient
      status, gestational age at surgery, fetal growth restriction, and co-twin fetal
      death were not risk factors. The rate of neurodevelopmental impairment
      (blindness, deafness, cerebral palsy, and/or a BDI-2 score <70) was 4%.
      CONCLUSION: Overall cognitive performance quotients were in the normal range,
      with risk factors for poor outcomes seen at the pregnancy and child levels.
      Clinical and socioeconomic characteristics can identify at-risk children who need
      additional interventions.

PMID- 24681291
TI  - Does prior hysteroscopy affect pregnancy outcome in primigravid infertile women?
AB  - OBJECTIVE: An increasing proportion of infertile women are subjected to
      hysteroscopy. The effect of hysteroscopy on the pregnancy rate in assisted
      reproduction has been demonstrated to be favorable, but cervical dilation in the
      course of hysteroscopy may have an adverse effect on pregnancy outcome. We sought
      to investigate the effect of hysteroscopy on the risk of early miscarriage,
      preterm delivery, low birthweight, and other complications of pregnancy. STUDY
      DESIGN: This was a longitudinal retrospective cohort study at a university
      hospital. Data of 654 first-time singleton pregnancies between January 1997 and
      March 2011 in women with primary infertility were retrieved from a prospective
      data collection. Four cohorts were constructed based on exposure to hysteroscopy
      and pregnancy outcome (early miscarriage vs live birth). The primary endpoint was
      the duration of pregnancy at 37 weeks. Pregnancy outcomes of 167 infertile
      patients exposed to cervical dilation and hysteroscopy were compared with those
      of 327 infertile women unexposed to hysteroscopy. RESULTS: The incidence of
      miscarriage, preterm birth, placenta previa, and premature rupture of membranes
      after maternal exposure to hysteroscopy was similar to that in women not exposed.
      CONCLUSION: Prior hysteroscopy in infertile women does not affect subsequent
      pregnancy outcome.

PMID- 24681293
TI  - MicroRNAs in vascular aging and atherosclerosis.
AB  - Lipid dysfunction, inflammation, immune response and advanced aging are major
      factors involved in the initiation and progression of atherosclerosis. MicroRNAs
      (miRNAs) have emerged as important regulators of gene expression that post
      transcriptionally modify cellular responses and function. MiRNA's are crucially
      involved in several vascular pathologies which show a clear association with
      increasing age (Dimmeler and Nicotera, 2013). Several studies have demonstrated
      that miRNA dysregulation has a crucial role in the development of atherosclerotic
      disease, encompassing every step from plaque formation to destabilization and
      rupture. This review will present the recent advances in the elucidation of the
      complex pathophysiological mechanisms in vascular aging by which miRNAs regulate
      the different phases of atherosclerotic process with a focus on endothelial cells
      and both, innate and adaptive immune systems. Furthermore, the future areas of
      research and potential clinical strategies will be discussed. 

PMID- 24681292
TI  - Non-coding RNA regulation of synaptic plasticity and memory: implications for
      aging.
AB  - Advancing age is associated with the loss of cognitive ability and vulnerability
      to debilitating mental diseases. Although much is known about the development of
      cognitive processes in the brain, the study of the molecular mechanisms governing
      memory decline with aging is still in its infancy. Recently, it has become
      apparent that most of the human genome is transcribed into non-coding RNAs
      (ncRNAs) rather than protein-coding mRNAs. Multiple types of ncRNAs are enriched
      in the central nervous system, and this large group of molecules may regulate the
      molecular complexity of the brain, its neurons, and synapses. Here, we review the
      current knowledge on the role of ncRNAs in synaptic plasticity, learning, and
      memory in the broader context of the aging brain and associated memory loss. We
      also discuss future directions to study the role of ncRNAs in the aging process. 

PMID- 24681294
TI  - Intranasal delivery of systemic-acting drugs: small-molecules and
      biomacromolecules.
AB  - As a non-invasive route, intranasal administration offers patient comfort and
      compliance which are hurdled in parenteral drug therapy. In addition, the current
      recognition that the high permeability and vascularization of nasal mucosa
      coupled to the avoidance of the first-pass elimination and/or gastrointestinal
      decomposition ensure higher systemic drug absorption than oral route has
      contributed to the growing interest for intranasal delivery of drugs that require
      considerable systemic exposure to exert their therapeutic actions (systemic
      acting drugs). Nevertheless, several features may hamper drug absorption through
      the nasal mucosa, particularly the drug molecular weight and intrinsic
      permeability, and, therefore, several strategies have been employed to improve
      it, propelling a constant challenge during nasal drug (formulation) development.
      This review will firstly provide an anatomical, histological and mechanistic
      overview of drug systemic absorption after nasal administration and the relevant
      aspects of the therapeutic interest and limitations of the intranasal systemic
      delivery. The current studies regarding the nasal application of systemic-acting
      small drugs (analgesic drugs, cardiovascular drugs and antiviral drugs) and
      biomacromolecular drugs (peptide/protein drugs and vaccines) will also be
      outlined, addressing drug pharmacokinetics and pharmacodynamic improvements. 

PMID- 24681295
TI  - Development of pH responsive novel emulsion adjuvant for oral immunization and in
      vivo evaluation.
AB  - The present work has been envisaged to develop a pH responsive multiple emulsion
      (W/O/W) adjuvant for successful antigen delivery via oral route. The formulation
      was prepared by double emulsion technique using squalene as oil phase and a
      combination of antigens and Quil A as internal aqueous phase. Squalene emulsion
      (O/W) adjuvants are well accepted for parenteral administration. Instead of using
      conventional surfactants, Quil A was incorporated in the internal aqueous
      compartment for the first time. The microscopic analysis confirmed the formation
      of the W/O/W multiple emulsions with globule diameter ranging from 7 to 12 MUm.
      Considerably, addition of Quil A resulted in marked improvement in both in vitro
      stability and immune response. Furthermore, addition of pectin to the external
      aqueous phase resulted in improved in vitro stability. A formulation with gel
      like structure was formed when pectin was used as stabilizer and also accounted
      with a significant increase in viscosity (from 275.3 cP to 330.4 cP) in the
      simulated gastric fluid, which reverts back to 290.2 cP after exposure to
      simulated intestinal fluid. Induction of strong mucosal and systemic immune
      response suggested that the developed formulation could be useful for the
      delivery of multiple biomolecules via oral route.

PMID- 24681296
TI  - Interactions of beta-blockers with model lipid membranes: molecular view of the
      interaction of acebutolol, oxprenolol, and propranolol with phosphatidylcholine
      vesicles by time-dependent fluorescence shift and molecular dynamics simulations.
AB  - Since pharmacokinetic and pharmacodynamic activities of drugs are often related
      to their interactions with biomembranes, it is of high interest to establish an
      approach for the characterization of these interactions at the molecular level.
      For the present study, beta-blockers (oxprenolol, propranolol, and acebutolol)
      were selected due to their well described nonspecific membrane effects (NME).
      Their interactions with model lipid membranes composed of
      palmitoyloleoylphosphatidylcholine (POPC) were studied using Time-Dependent
      Fluorescence Shift (TDFS) and Generalized Polarization (GP) as well as molecular
      dynamics (MD) simulations. Liposomal vesicles were labeled with fluorescent
      membrane polarity probes (Laurdan, Prodan, and Dtmac). Increasing beta-blocker
      concentrations (0-10 mM for acebutolol and oxprenolol, and 0-1.5 mM for
      propranolol) significantly rigidifies the lipid bilayer at the glycerol and
      headgroup level, which was detected in the steady-state and in the time-resolved
      fluorescence data. The effects of propranolol were considerably stronger than
      those of the two other beta-blockers. The addition of fluorescent probes
      precisely located at different levels within the lipid bilayer revealed the
      insertion of the beta-blockers into the POPC bilayer at the glycerol backbone
      level, which was further confirmed by MD simulations in the case of propranolol.

PMID- 24681297
TI  - Imaging and morphology in reproductive toxicology - progress to date and future
      directions.
AB  - This review looks at the recent development and application of imaging techniques
      for the morphological examination of fetuses from preclinical regulatory
      reproductive toxicology studies. Full replacement of the examination methods
      currently used in routine studies (microdissection, Bouin's fluid
      fixation/sectioning and alizarin red S/alcian blue preparations) by imaging
      techniques has yet to be achieved. Progress, especially in the application of
      micro-CT for skeletal examination, has been made but challenges, particularly the
      financial investment required, remain. Despite this apparent lack of progress the
      application of imaging techniques to "non-routine" preclinical reproductive
      toxicology studies has been used to good effect. The ability to acquire multiple
      images over a time course i.e. longitudinally has enabled the fate, particularly
      of skeletal features, to be determined. The additional evidence gained from such
      studies can be used to better inform the prenatal developmental hazard assessment
      of test compounds. 

PMID- 24681299
TI  - Economic analysis of social services for the elderly in Serbia: two sides of the
      same coin.
AB  - According to demographic trends, the ratio of senior citizens in the overall
      population of the Republic of Serbia is rising. This generates the need to create
      socially acceptable and economically sustainable models for the protection of the
      elderly. The goal of this paper is to stress the necessity of analyzing and
      evaluating the efficiency of social protection services aimed at senior citizens.
      The first part of the paper underlines the need for economic analysis of these
      services; while the second part features the analysis of the two most frequently
      provided services for the elderly in Serbia: admission to social protection
      institutions and home care for senior citizens. Based on the research results,
      the paper also provides a comparative overview of the efficiency of the services
      mentioned. This overview clearly confirms that both services prove to be
      economically justifiable from a social perspective; nevertheless, it also
      indicates that the cost of home care per user is considerably lower than the cost
      of putting a senior citizen into a nursing home. After presenting and discussing
      the results of the studies, the paper also offers recommendations aimed at
      enhancing the development and sustainability of the social protection system for
      the elderly in Serbia. 

PMID- 24681300
TI  - Gasification of torrefied Miscanthus * giganteus in an air-blown bubbling
      fluidized bed gasifier.
AB  - Torrefaction is suggested to be an effective method to improve the fuel
      properties of biomass and gasification of torrefied biomass should provide a
      higher quality product gas than that from unprocessed biomass. In this study,
      both raw and torrefied Miscanthus * giganteus (M*G) were gasified in an air-blown
      bubbling fluidized bed (BFB) gasifier using olivine as the bed material. The
      effects of equivalence ratio (ER) (0.18-0.32) and bed temperature (660-850
      degrees C) on the gasification performance were investigated. The results
      obtained suggest the optimum gasification conditions for the torrefied M * G are
      ER 0.21 and 800 degrees C. The product gas from these process conditions had a
      higher heating value (HHV) of 6.70 MJ/m(3), gas yield 2m(3)/kg biomass (H2 8.6%,
      CO 16.4% and CH4 4.4%) and cold gas efficiency 62.7%. The comparison between raw
      and torrefied M * G indicates that the torrefied M * G is more suitable BFB
      gasification.

PMID- 24681298
TI  - Evolution of acquired resistance to anti-cancer therapy.
AB  - Acquired drug resistance is a major limitation for the successful treatment of
      cancer. Resistance can emerge due to a variety of reasons including host
      environmental factors as well as genetic or epigenetic alterations in the cancer
      cells. Evolutionary theory has contributed to the understanding of the dynamics
      of resistance mutations in a cancer cell population, the risk of resistance pre
      existing before the initiation of therapy, the composition of drug cocktails
      necessary to prevent the emergence of resistance, and optimum drug administration
      schedules for patient populations at risk of evolving acquired resistance. Here
      we review recent advances towards elucidating the evolutionary dynamics of
      acquired drug resistance and outline how evolutionary thinking can contribute to
      outstanding questions in the field. 

PMID- 24681301
TI  - Long-term performance and microbial ecology of a two-stage PN-ANAMMOX process
      treating mature landfill leachate.
AB  - Long-term performance of a two-stage partial nitritation (PN)-anaerobic ammonium
      oxidation (ANAMMOX) process treating mature landfill leachate was investigated.
      Stable partial nitritation performance was achieved in a sequencing batch reactor
      (SBR) using endpoint pH control, providing an effluent with a ratio of NO2(-)
      N/NH4(+)-N at 1.23 +/- 0.23. High rate nitrogen removal over 4 kg N/m(3)/d was
      observed in the ANAMMOX reactor in the first three months. However, during long
      term operation, the ANAMMOX reactor can only stably operate under nitrogen load
      of 1 kg N/m(3)/d, with 85 +/- 1% of nitrogen removal. The ammonium oxidizing
      bacteria (AOB) in the PN-SBR were mainly affiliated to Nitrosomonas sp. IWT514,
      Nitrosomonas eutropha and Nitrosomonas eutropha, the anaerobic ammonium oxidizing
      bacteria (AnAOB) in the ANAMMOX reactor were mainly affiliated to Kuenenia
      stuttgartiensis.

PMID- 24681303
TI  - Pathogenesis of a genotype C strain of bovine parainfluenza virus type 3
      infection in albino guinea pigs.
AB  - Bovine parainfluenza virus type 3 (BPIV3) is one of the most important of the
      known viral respiratory tract agents of both young and adult cattle and
      widespread among cattle around the world. Up to present, three genotypes A, B and
      C of BPIV3 have been described on the basis of genetic and phylogenetic analysis
      and only limited studies on the pathogenesis of the genotype A of BPIV3 infection
      in calves and laboratory animals have been performed. The report about
      experimental infections of the genotypes B and C of BPIV3 in laboratory animals
      and calves was scant. Therefore, an experimental infection of guinea pigs with
      the Chinese BPIV3 strain SD0835 of the genotype C was performed. Sixteen guinea
      pigs were intranasally inoculated with the suspension of SD0835, while eight
      control guinea pigs were also intranasally inoculated with the same volume of
      supernatant from uninfected MDBK cells. The virus-inoculated guinea pigs
      displayed a few observable clinical signs that were related to the respiratory
      tract disease and two of the sixteen experimentally infected guinea pigs died at
      2 and 3 days post inoculation (PI), respectively, and apparent gross pneumonic
      lesions were observed at necropsy. The gross pneumonic lesions in guinea pigs
      inoculated with SD0835 consisted of dark red, slightly depressed, irregular areas
      of consolidation in the lung lobes from the second to 9th day of infection at
      necropsy, and almost complete consolidation and atelectasis of the lung lobes
      were seen at 7 days PI. Histopathological changes including alveoli septa
      thickening and focal cellulose pneumonia were also observed in the lungs of
      guinea pigs experimentally infected with SD0835. Viral replication was detectable
      by virus isolation and titration, real-time RT-PCR and immunohistochemistry (IHC)
      staining in the respiratory tissues of guinea pigs as early as 24h after
      intranasal inoculation with SD0835. The results of virus isolation and titration
      showed that guinea pigs were permissive for SD0835 replication and exhibited a
      higher virus replication level in both lungs and tracheas. As well, the results
      of IHC staining implicated that the lungs and tracheas were the major tissues in
      which SD0835 replicated. Virus-specific serum neutralizing antibodies against
      BPIV3 were detected in virus-inoculated guinea pigs. The aforementioned results
      indicated that BPIV3 strain SD0835 of the genotype C was pathogenic to guinea
      pigs and could cause a few observable clinical signs, and gross and histologic
      lesions in virus-inoculated guinea pigs. Thus guinea pig is an ideal laboratory
      animal infection model for BPIV3 and would cast more light on the genotype C of
      BPIV3 infection process, in vivo tropism and pathogenesis or serve as a useful
      system for monitoring the pathogenesis of SD0835 and other BPIV3 isolates.

PMID- 24681302
TI  - Demographics, bystander CPR, and AED use in out-of-hospital pediatric arrests.
AB  - BACKGROUND: In 2005 the American Heart Association released guidelines calling
      for routine use of automated external defibrillators during pediatric out-of
      hospital arrest. The goal of this study was to determine if these guidelines are
      used during resuscitations. METHODS: We conducted a secondary analysis of
      prospectively collected data from 29 U.S. cities that participate in the Cardiac
      Arrest Registry to Enhance Survival (CARES). Patients were included if they were
      older than 1 year of age and had a documented resuscitation attempt from October
      1, 2005 through December 31, 2009 from an arrest presumed to be cardiac in
      nature. Hierarchical multivariable logistic regression analysis was used to
      estimate the associations between age, demographic factors, and AED use. RESULTS:
      129 patients were 1-8 years of age (younger children), 88 patients were 9-17
      years of age (older children), and 19,338 patients were >=18 years of age
      (adults). When compared to adults, younger children were less likely to be found
      in a shockable rhythm (young children 11.6%, adults 23.7%) and were less likely
      to have an AED used (young children 16.3%, adults 28.3%). Older children had a
      similar prevalence of shockable rhythms as adults (31.8%) and AED use (20.5%). A
      multivariable analysis demonstrated that, when compared to adults, younger
      children had decreased odds of having an AED used (OR 0.42, 95% CI 0.26-0.69),
      but there was no difference in AED use among older children and adults.
      CONCLUSIONS: Young children suffering from presumed out-of-hospital cardiac
      arrests are less likely to have a shockable rhythm when compared to adults, and
      are less likely to have an AED used during resuscitation.

PMID- 24681304
TI  - Qualitative detection of class IIa bacteriocinogenic lactic acid bacteria from
      traditional Chinese fermented food using a YGNGV-motif-based assay.
AB  - In the present study, a YGNGV-motif-based assay was developed and applied. Given
      that there is an increasing demand for natural preservatives, we set out to
      obtain lactic acid bacteria (LAB) that produce bacteriocins against Gram-positive
      and Gram-negative bacteria. We here isolated 123 LAB strains from 5 types of
      traditional Chinese fermented food and screened them for the production of
      bacteriocins using the agar well diffusion assay (AWDA). Then, to acquire LAB
      producing class IIa bacteriocins, we used a YGNGV-motif-based assay that was
      based on 14 degenerate primers matching all class IIa bacteriocin-encoding genes
      currently deposited in NCBI. Eight of the LAB strains identified by AWDA could
      inhibit Gram-positive and Gram-negative bacteria; 5 of these were YGNGV-amplicon
      positive. Among these 5 isolates, amplicons from 2 strains (Y31 and Y33) matched
      class IIa bacteriocin genes. Strain Y31 demonstrated the highest inhibitory
      activity and the best match to a class IIa bacteriocin gene in NCBI, and was
      identified as Enterococcus faecium. The bacteriocin from Enterococcus avium Y33
      was 100% identical to enterocin P. Both of these strains produced bacteriocins
      with strong antimicrobial activity against Listeria monocytogenes, Escherichia
      coli, and Bacillus subtilis, hence these bacteriocins hold promise as potential
      bio-preservatives in the food industry. These findings also indicated that the
      YGNGV-motif-based assay used in this study could identify novel class IIa
      bacteriocinogenic LAB, rapidly and specifically, saving time and labour by by
      passing multiple separation and purification steps. 

PMID- 24681305
TI  - Adaptation of Ti(III)-NTA colorimetric assay for use in detecting microbial
      demethylation of lignin and lignin derived compounds in aerobic conditions.
AB  - An anaerobic colorimetric assay for quantifying microbial demethylation activity
      was adapted for aerobic use in studying lignin and lignin-derived compounds.
      Standard curves of 0-500MUM pyrocatechol with and without 0.3% lignin
      demonstrated the use in either case. This method detects demethylation products
      up to 500MUM without using additional dilutions. 

PMID- 24681306
TI  - Rapid detection of Ganoderma-infected oil palms by microwave ergosterol
      extraction with HPLC and TLC.
AB  - Detection of basal stem rot (BSR) by Ganoderma of oil palms was based on foliar
      symptoms and production of basidiomata. Enzyme-Linked Immunosorbent Assays
      Polyclonal Antibody (ELISA-PAB) and PCR have been proposed as early detection
      methods for the disease. These techniques are complex, time consuming and have
      accuracy limitations. An ergosterol method was developed which correlated well
      with the degree of infection in oil palms, including samples growing in
      plantations. However, the method was capable of being optimised. This current
      study was designed to develop a simpler, more rapid and efficient ergosterol
      method with utility in the field that involved the use of microwave extraction.
      The optimised procedure involved extracting a small amount of Ganoderma, or
      Ganoderma-infected oil palm suspended in low volumes of solvent followed by
      irradiation in a conventional microwave oven at 70 degrees C and medium high
      power for 30s, resulting in simultaneous extraction and saponification.
      Ergosterol was detected by thin layer chromatography (TLC) and quantified using
      high performance liquid chromatography with diode array detection. The TLC method
      was novel and provided a simple, inexpensive method with utility in the field.
      The new method was particularly effective at extracting high yields of ergosterol
      from infected oil palm and enables rapid analysis of field samples on site,
      allowing infected oil palms to be treated or culled very rapidly. Some
      limitations of the method are discussed herein. The procedures lend themselves to
      controlling the disease more effectively and allowing more effective use of land
      currently employed to grow oil palms, thereby reducing pressure to develop new
      plantations. 

PMID- 24681307
TI  - Bifunctional role of a pattern recognition molecule beta-1,3 glucan binding
      protein purified from mangrove crab Episesarma tetragonum.
AB  - beta-1,3-Glucan binding protein (beta-GBP) was purified from the haemolymph of
      Episesarma tetragonum by affinity chromatography with epoxy-activated laminarin
      sepharose CL-6B column. E. tetragonum beta-GBP exhibits a single band with a
      molecular weight of 100 kDa on SDS-PAGE and a pI of 5.9 in isoelectric focusing
      (IEF). The circular dichroism (CD) spectra result of E. tetragonum beta-GBP
      indicates that the negative ellipticity bands near 220 nm and 208 nm correspond
      to the beta-sheets in the secondary structure. Functional analysis results
      demonstrate that the purified E. tetragonum beta-GBP agglutinates fungal cells
      (Candida albicans) containing beta-glucan. This recognition and binding
      specificity leads to the activation of the prophenoloxidase (ProPO) cascade and
      enhance the phenoloxidase (PO) activity in a dose-dependent manner. Our finding
      discloses new insights in the ProPO activation and fungal agglutination of
      purified E. tetragonum beta-GBP. It seems to play a significant role in microbial
      uncovering mechanism in invertebrates.

PMID- 24681308
TI  - Development and evaluation of PEGylated Enoxaparin: a novel approach for enhanced
      anti-Xa activity.
AB  - Enoxaparin (ENX) is one of the most widely prescribed low molecular weight
      heparin inprophylaxis and treatment of venous thromboembolism. In this study,
      Enoxaparin-PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene
      glycol (PEG) and evaluated for its potential for extended duration of action. The
      esterification of the carboxyl groups of the drug moiety with the hydroxyl groups
      of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX
      conjugate was purified by dialysis and characterized by Fourier transform
      infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance ((1)H NMR) and
      matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques.
      FTIR analysis revealed frequency of the carbonyl group in accord with ester
      linkage formation between the drug and the PEG moiety. (1)H NMR of the conjugate
      showed significant change in the chemical shift further indicative of ENX and PEG
      chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z
      confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited
      considerable enhancement in anti-Xa activity (by three-folds) in comparison to
      free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX.
      Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of
      ENX with a potential for decreased dosing frequency. 

PMID- 24681309
TI  - When music tempo affects the temporal congruence between physical practice and
      motor imagery.
AB  - When people listen to music, they hear beat and a metrical structure in the
      rhythm; these perceived patterns enable coordination with the music. A clear
      correspondence between the tempo of actual movement (e.g., walking) and that of
      music has been demonstrated, but whether similar coordination occurs during motor
      imagery is unknown. Twenty participants walked naturally for 8m, either
      physically or mentally, while listening to slow and fast music, or not listening
      to anything at all (control condition). Executed and imagined walking times were
      recorded to assess the temporal congruence between physical practice (PP) and
      motor imagery (MI). Results showed a difference when comparing slow and fast time
      conditions, but each of these durations did not differ from soundless condition
      times, hence showing that body movement may not necessarily change in order to
      synchronize with music. However, the main finding revealed that the ability to
      achieve temporal congruence between PP and MI times was altered when listening to
      either slow or fast music. These data suggest that when physical movement is
      modulated with respect to the musical tempo, the MI efficacy of the corresponding
      movement may be affected by the rhythm of the music. Practical applications in
      sport are discussed as athletes frequently listen to music before competing while
      they mentally practice their movements to be performed. 

PMID- 24681311
TI  - Characterizations of diverse mole of pure and Ni-doped alpha-Fe2O3 synthesized
      nanoparticles through chemical precipitation route.
AB  - In the present study, an attempt has been made for characterization and synthesis
      of pure and Ni-doped alpha-Fe2O3 (hematite) nanoparticles by chemical
      precipitation method. The synthesized products have been studied by X-ray
      diffraction (X-RD), Fourier transform infrared (FTIR) spectroscopy, UV-Vis
      diffuse reflectance spectroscopy (UV-Vis DRS), vibrating sample magnetometer
      (VSM) and scanning electron microscopy (SEM) techniques. The estimated average
      diameter of alpha-Fe2O3 nanoparticles were calculated by using the Debye-Scherrer
      equation and established as 31 nm. SEM micrographs showed the surface morphology
      as well as structures and particles distributions of synthesized samples. The UV
      Vis DRS showed the indirect and direct band gap energies of pure and Ni-doped
      alpha-Fe2O3, these were reduced from 1.9847 to 1.52 eV and 2.0503 to 1.76 eV
      respectively. This result suggested the dopant enhanced the semiconducting
      behavior of iron oxide nanoparticles to an extent proportional to its nickel
      doped in the alpha-Fe2O3. Further, the magnetic properties of the pure and doped
      samples were investigated by vibrating sample magnetometer (VSM) and evaluated
      the information of pure and doped samples exhibited saturated hysteresis loop at
      room temperature, which is indicating that the weak ferromagnetism in nature of
      our synthesized samples. In addition, it has been found from the magnetization
      hysteresis curves of Ni-doping, resulting from increased the saturation of
      magnetization and reduced the coercivity of used samples. Therefore, the present
      study showed the reduction in band gap energies and coercive field for alpha
      Fe2O3 nanoparticles due to nickel doped.

PMID- 24681310
TI  - Minireview: DNA replication in plant mitochondria.
AB  - Higher plant mitochondrial genomes exhibit much greater structural complexity
      compared to most other organisms. Unlike well-characterized metazoan
      mitochondrial DNA (mtDNA) replication, an understanding of the mechanism(s) and
      proteins involved in plant mtDNA replication remains unclear. Several plant mtDNA
      replication proteins, including DNA polymerases, DNA primase/helicase, and
      accessory proteins have been identified. Mitochondrial dynamics, genome
      structure, and the complexity of dual-targeted and dual-function proteins that
      provide at least partial redundancy suggest that plants have a unique model for
      maintaining and replicating mtDNA when compared to the replication mechanism
      utilized by most metazoan organisms. 

PMID- 24681312
TI  - TDDFT study of the polarity controlled ion-pair separation in an excited-state
      proton transfer reaction.
AB  - 6-Hydroxyquinoline (6HQ) is an ideal photoacid system for exploring excited-state
      proton transfer (ESPT) reactions. We have previously (Mahata et al. (2002)) shown
      that the ESPT reaction between 6HQ and trimethylamine (TMA) leads to an "unusual"
      emission in the 440-450 nm range, containing two decay components (~5 ns and ~12
      ns). The observed results suggest the presence of a contact ion-pair and a
      solvent separated ion-pair. In this work, density functional theory (DFT) and
      time-dependent density functional theory (TD-DFT) have been employed to study the
      nature of the contact ion-pair formed between 6HQ and TMA and to determine why
      the decay component ~12 ns is absent in a non-polar solvent. Calculations of the
      hydrogen-bonded complexes formed between 6HQ and TMA and its ESPT reaction
      product, namely 6HQ-TMA and 6HQ-TMA-PT, respectively, have been carried out, both
      in the electronic ground and excited states. Moreover, by using the CPCM model,
      different dielectric constants have been introduced into the calculations. On
      increasing the dielectric constant, the hydrogen bond in 6HQ-TMA-PT becomes
      weaker and the hydrogen bond length becomes larger; this effectively facilitates
      the proton transfer reaction and formation of separated ion-pair. Thus, the
      separation and diffusion of the contact ion-pair can be controlled by changing
      the polarity of the surroundings.

PMID- 24681313
TI  - Dendrophthoe falcata (L.f) Ettingsh (Neem mistletoe): a potent bioresource to
      fabricate silver nanoparticles for anticancer effect against human breast cancer
      cells (MCF-7).
AB  - Fabrication of metal nano scale particles through environmentally acceptable
      greener route has been focused with much interest in the present scenario. In
      this study aqueous leaf extract of mistletoe Dendrophthoe falcata (L.f) Ettingsh
      was successfully employed as a reducing and stabilizing agent to fabricate
      nanosilver particles (AgNPs) for biomedical applications. Various reactions
      conditions such as temperature, pH, concentration of metal ion, incubation time
      and stoichiometric proportion of the reaction mixture were optimized to attain
      narrow size range particles with maximum synthesis rate. Fabricated crystalline
      AgNPs with spherical structure (5-45 nm) were characterized with UV-Visible
      spectroscopy, Field emission scanning electron microscope (FESEM), High
      resolution transmission electron microscope (HRTEM) and Selected area diffraction
      pattern (SEAD). Further the fabricated AgNPs were studied for their stability and
      surface chemistry through Fourier transform infrared spectroscopy (FTIR), Energy
      dispersive X-ray spectroscopy (EDAX) and inductively coupled plasma optical
      emission spectroscopy (ICP-OES). Moreover, fabricated AgNPs and aqueous leaf
      extract were assessed for their cytotoxicity effect against human breast
      carcinoma cell line (MCF-7). It is concluded that colloidal AgNPs can be
      developed as an imminent candidature for cancer therapy.

PMID- 24681314
TI  - The molecular structure of the borate mineral rhodizite (K, Cs)Al4Be4(B, Be)12O28
      -a vibrational spectroscopic study.
AB  - We have studied the borate mineral rhodizite (K, Cs)Al4Be4(B, Be)12O28 using a
      combination of DEM with EDX and vibrational spectroscopic techniques. The mineral
      occurs as colorless, gray, yellow to white crystals in the triclinic crystal
      system. The studied sample is from the Antandrokomby Mine, Sahatany valley,
      Madagascar. The mineral is prized as a semi-precious jewel. Semi-quantitative
      chemical composition shows a Al, Ca, borate with minor amounts of K, Mg and Cs.
      The mineral has a characteristic borate Raman spectrum and bands are assigned to
      the stretching and bending modes of B, Be and Al. No Raman bands in the OH
      stretching region were observed. 

PMID- 24681315
TI  - Two photon absorption energy transfer in the light-harvesting complex of
      photosystem II (LHC-II) modified with organic boron dye.
AB  - The plant light-harvesting complexes of photosystem II (LHC-II) play important
      roles in collecting solar energy and transferring the energy to the reaction
      centers of photosystems I and II. A two photon absorption compound, 4
      (bromomethyl)-N-(4-(dimesitylboryl)phenyl)-N-phenylaniline (DMDP-CH2Br), was
      synthesized and covalently linked to the LHC-II in formation of a LHC-II-dye
      complex, which still maintained the biological activity of LHC-II system. Under
      irradiation with femtosecond laser pulses at 754 nm, the LHC-II-dye complex can
      absorb two photons of the laser light effectively compared with the wild type LHC
      II. The absorbed excitation energy is then transferred to chlorophyll a with an
      obvious fluorescence enhancement. The results may be interesting and give
      potentials for developing hybrid photosystems.

PMID- 24681316
TI  - An experimental and theoretical study of the amino acid side chain Raman bands in
      proteins.
AB  - The Raman spectra of a series of tripeptides with the basic formula GlyAAGly
      where the central amino acid (AA) was tryptophan, tyrosine, phenylalanine,
      glycine, methionine, histidine, lysine and leucine were measured in H2O. The
      theoretical Raman spectra obtained using density functional theory (DFT)
      calculations at the B3LYP/6-311+G(2df,2pd) level of theory allows a precise
      attribution of the vibrational bands. The experimental results show that there is
      a blue shift in the frequencies of several bands of the amino acid side chains in
      tripeptides compared to free amino acids, especially in the case of AAs
      containing aromatic rings. On the other hand, a very good agreement was found
      between the Raman bands of AA residues in tripeptides and those measured on three
      model proteins: bovine serum albumin, beta-lactoglobulin and lysozyme. The
      present analysis contributes to an unambiguous interpretation of the protein
      Raman spectra that is useful in monitoring the biological reactions involving AA
      side chains alteration. 

PMID- 24681317
TI  - Fabrication and characterization of silver nanoparticles using Delonix elata leaf
      broth.
AB  - The synthesis of nanoparticles from plant sources has proved to be an effective
      and alternative method for the novel production of nanoparticles. This paper
      reports the bioreduction of silver nitrate into silver nanoparticle by the leaf
      extract of Delonix elata. The synthesized silver nanoparticles were characterized
      by UV-visible (UV-vis) spectroscopy, Fourier infrared spectroscopy (FT-IR), X-ray
      diffraction (XRD), Scanning Electron Microscopy (SEM) coupled with Energy
      Dispersive Spectroscopy (EDS), high resolution transmission electron microscope
      (HRTEM). In addition the size of the NPs was calculated by using Malvern
      Zetasizer and the stability by zeta potential. UV-vis spectra show the surface
      plasmon resonance (SPR) at 432 nm. This reveals the reduction of silver ions
      (Ag(+)) into silver (Ag degrees ) and indicating the formation of silver
      nanoparticles (AgNPs). SEM analysis revealed the spherical shape of the particles
      with sizes in the range of 35-45 nm and EDS spectrum confirmed the presence of
      silver along with other elements in the plant metabolite. The XRD analysis showed
      that the AgNPs are crystalline in nature and have face-centered cubic structure.
      FT-IR spectra show the existence of biomolecules responsible for the reduction of
      silver nitrate. The size of the AgNPs estimated from particle size distribution
      curve shows the 70 nm. The zeta potential of AgNPs was found to be -18 mV,
      indicating the dispersion and stability.

PMID- 24681318
TI  - Growth and characterization of Ni(x)Zn(1-x)SO4.7H2O single crystals.
AB  - NiSO4.7H2O (morenosite) and ZnSO4.7H2O (goslarite) are hydrogen bonded crystals
      having wide applications in various fields. In an attempt to understand the
      formation and properties of mixed crystals based on NiSO4.7H2O and ZnSO4.7H2O, we
      have grown by the free evaporation method at room temperature and characterized
      Ni(x)Zn(1-x)SO4.7H2O single crystals (with x having the values 0.0, 0.2, 0.4,
      0.5, 0.6, 0.8 and 1.0). The grown crystals were characterized chemically and
      structurally by carrying out density, X-ray powder diffraction, and atomic
      absorption and Fourier transform infrared spectral measurements. The grown
      crystals exhibit good optical transparency in the wavelength range 210-1100 nm.
      The second harmonic generation measurements indicate a maximum efficiency for the
      mixed crystal with x = 0.5. Results of microhardness measurements follow the
      normal indentation size effect. Electrical (AC and DC) measurements indicate that
      the grown crystals exhibit a normal dielectric behavior and the electrical
      conduction is understood to be due to the protonic movement. The present study
      indicates that the mixed crystals with x = 0.2 and 0.5 are not only promising
      nonlinear optical materials but also useful as low dielectric constant materials.

PMID- 24681319
TI  - Disaggregation induced solvatochromic switch: a study of dansylated polyglycerol
      dendrons in binary solvent mixture.
AB  - A reversal in solvatochromic behaviour was observed in second and third
      generation glycerol based dansylated polyether dendrons in water on addition of a
      second solvent like methanol or acetonitrile. Below a certain percentage of the
      nonaqueous solvent there is a negative-solvatochromism observed and above that
      there is a switch to positive-solvatochromism. The negative-solvatochromism is
      attributed to the progressive disaggregation of the dendron aggregates by the
      nonaqueous solvent component. Once the disaggregation process is complete,
      positive-solvatochromism is exhibited by the dendron monomers. Higher the
      hydrophobicity of the dendron more is the amount of the second solvent required
      for disaggregation. 

PMID- 24681320
TI  - Eco-friendly synthesis of silver and gold nanoparticles with enhanced
      bactericidal activity and study of silver catalyzed reduction of 4-nitrophenol.
AB  - The present study reports a simple and robust method for synthesis of silver and
      gold nanoparticles using Coleus forskohlii root extract as reducing and
      stabilizing agent. Stable silver nanoparticles (AgNPs) and gold nanopoarticles
      (AuNPs) were formed on treatment of an aqueous silver nitrate (AgNO3) and
      chloroauric acid (HAuCl4) solutions with the root extract. The nanoparticles
      obtained were characterized by UV-Visible spectroscopy, Transmission electron
      microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared
      spectroscopy (FT-IR). UV-Vis and TEM analysis indicate that with higher
      quantities of root extract, the interaction is enhanced leading to size reduction
      of spherical metal nanoparticles. XRD confirms face-centered cubic phase and the
      diffraction peaks can be attributed to (111), (200), (222) and (311) planes for
      these nanoparticles. These synthesized Ag and Au nanoparticles were found to
      exhibit excellent bactericidal activity against clinically isolated selected
      pathogens such as Escherichia coli (E. coli), Pseudomonas aeruginosa (P.
      aeruginosa) and Staphylococcus aureus (S. aureus). The synthesized AgNPs were
      also found to function as an efficient green catalyst in the reduction of
      anthropogenic pollutant 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) by sodium
      borohydride, which was apparent from the periodical color change from bright
      yellow to colorless, after the addition of AgNPs. 

PMID- 24681321
TI  - Synthesis, crystal structure, fluorescence and electrochemical studies of a new
      tridentate Schiff base ligand and its nickel(II) and palladium(II) complexes.
AB  - A new unsymmetrical tridentate Schiff base ligand was derived from the 1:1M
      condensation of ortho-vanillin with 2-mercaptoethylamine. Nickel and palladium
      complexes were obtained by the reaction of the tridentate Schiff base ligand with
      nickel(II) acetate tetrahydrate and palladium(II) acetate in 2:1M ratio. In
      nickel and palladium complexes the ligand was coordinated to metals via the imine
      N and enolic O atoms. The S groups of Schiff bases were not coordinated to the
      metals and S-S coupling was occured. The complexes have been found to possess 1:2
      Metal:Ligand stoichiometry and the molar conductance data revealed that the metal
      complexes were non-electrolytes. The complexes exhibited octahedral coordination
      geometry. The emission spectra of the ligand and its complexes were studied in
      methanol. Electrochemical properties of the ligand and its metal complexes were
      investigated in the CH3CN solvent at the 100 mV s(-1) scan rate. The ligand and
      metal complexes showed both reversible and quasi-reversible processes at this
      scan rate. The Schiff base and its complexes have been characterized by IR, (1)H
      NMR, UV/Vis, elemental analyses and conductometry. The crystal structure of
      nickel complex has been determined by single crystal X-ray diffraction.

PMID- 24681322
TI  - Modelling nutrition across organizational levels: from individuals to
      superorganisms.
AB  - The Geometric Framework for nutrition has been increasingly used to describe how
      individual animals regulate their intake of multiple nutrients to maintain target
      physiological states maximizing growth and reproduction. However, only a few
      studies have considered the potential influences of the social context in which
      these nutritional decisions are made. Social insects, for instance, have evolved
      extreme levels of nutritional interdependence in which food collection,
      processing, storage and disposal are performed by different individuals with
      different nutritional needs. These social interactions considerably complicate
      nutrition and raise the question of how nutrient regulation is achieved at
      multiple organizational levels, by individuals and groups. Here, we explore the
      connections between individual- and collective-level nutrition by developing a
      modelling framework integrating concepts of nutritional geometry into individual
      based models. Using this approach, we investigate how simple nutritional
      interactions between individuals can mediate a range of emergent collective-level
      phenomena in social arthropods (insects and spiders) and provide examples of
      novel and empirically testable predictions. We discuss how our approach could be
      expanded to a wider range of species and social systems. 

PMID- 24681323
TI  - Rheological measurements on different types of sewage sludge for pumping design.
AB  - Sewage sludge pumping could represent an optimal solution to assure adequate
      treatment of sludge in centralized plants, with a consequent reduction of the
      environmental impact of sludge disposal (volume, odour, putrescence), because
      small wastewater treatment plants usually do not provide an adequate treatment
      due to high costs. An accurate knowledge of rheological parameters is required to
      compute head loss for pipeline design, but only few data are available. In order
      to circumvent the problem of the scarcity of sludge rheological data, we have
      performed tests on different types of sludge, with solids concentration and
      temperature in the typical range of a conventional wastewater treatment plant.
      Bingham rheological parameters and sludge thixotropy values have been processed
      by regression analysis to identify their dependence on solids concentration or
      temperature. The results of this study allow the definition of guidelines and
      optimal strategies for designers in order to reduce pumping costs. 

PMID- 24681324
TI  - TRDistiller: a rapid filter for enrichment of sequence datasets with proteins
      containing tandem repeats.
AB  - The dramatic growth of sequencing data evokes an urgent need to improve
      bioinformatics tools for large-scale proteome analysis. Over the last two
      decades, the foremost efforts of computer scientists were devoted to proteins
      with aperiodic sequences having globular 3D structures. However, a large portion
      of proteins contain periodic sequences representing arrays of repeats that are
      directly adjacent to each other (so called tandem repeats or TRs). These proteins
      frequently fold into elongated fibrous structures carrying different fundamental
      functions. Algorithms specific to the analysis of these regions are urgently
      required since the conventional approaches developed for globular domains have
      had limited success when applied to the TR regions. The protein TRs are
      frequently not perfect, containing a number of mutations, and some of them cannot
      be easily identified. To detect such "hidden" repeats several algorithms have
      been developed. However, the most sensitive among them are time-consuming and,
      therefore, inappropriate for large scale proteome analysis. To speed up the TR
      detection we developed a rapid filter that is based on the comparison of
      composition and order of short strings in the adjacent sequence motifs. Tests
      show that our filter discards up to 22.5% of proteins which are known to be
      without TRs while keeping almost all (99.2%) TR-containing sequences. Thus, we
      are able to decrease the size of the initial sequence dataset enriching it with
      TR-containing proteins which allows a faster subsequent TR detection by other
      methods. The program is available upon request. 

PMID- 24681325
TI  - Crystallographic snapshot of the Escherichia coli EnvZ histidine kinase in an
      active conformation.
AB  - Sensor histidine kinases are important sensors of the extracellular environment
      and relay signals via conformational changes that trigger autophosphorylation of
      the kinase and subsequent phosphorylation of a response regulator. The exact
      mechanism and the regulation of this protein family are a matter of ongoing
      investigation. Here we present a crystal structure of a functional chimeric
      protein encompassing the entire catalytic part of the Escherichia coli EnvZ
      histidine kinase, fused to the HAMP domain of the Archaeoglobus fulgidus Af1503
      receptor. The construct is thus equivalent to the full cytosolic part of EnvZ.
      The structure shows a putatively active conformation of the catalytic domain and
      gives insight into how this conformation could be brought about in response to
      sensory input. Our analysis suggests a sequential flip-flop autokinase mechanism.

PMID- 24681326
TI  - Provider payment methods and health worker motivation in community-based health
      insurance: a mixed-methods study.
AB  - In a community-based health insurance (CBHI) introduced in 2004 in Nouna health
      district, Burkina Faso, poor perceived quality of care by CBHI enrollees has been
      a key factor in observed high drop-out rates. The poor quality perceptions have
      been previously attributed to health worker dissatisfaction with the provider
      payment method used by the scheme and the resulting financial risk of health
      centers. This study applied a mixed-methods approach to investigate how health
      workers working in facilities contracted by the CBHI view the methods of provider
      payment used by the CBHI. In order to analyze these relationships, we conducted
      23 in-depth interviews and a quantitative survey with 98 health workers working
      in the CBHI intervention zone. The qualitative in-depth interviews identified
      that insufficient levels of capitation payments, the infrequent schedule of
      capitation payment, and lack of a payment mechanism for reimbursing service fees
      were perceived as significant sources of health worker dissatisfaction and loss
      of work-related motivation. Combining qualitative interview and quantitative
      survey data in a mixed-methods analysis, this study identified that the declining
      quality of care due to the CBHI provider payment method was a source of
      significant professional stress and role strain for health workers. Health
      workers felt that the following five changes due to the provider payment methods
      introduced by the CBHI impeded their ability to fulfill professional roles and
      responsibilities: (i) increased financial volatility of health facilities, (ii)
      dissatisfaction with eligible costs to be covered by capitation; (iii) increased
      pharmacy stock-outs; (iv) limited financial and material support from the CBHI;
      and (v) the lack of mechanisms to increase provider motivation to support the
      CBHI. To address these challenges and improve CBHI uptake and health outcomes in
      the targeted populations, the health care financing and delivery model in the
      study zone should be reformed. We discuss concrete options for reform based on
      the study findings. 

PMID- 24681327
TI  - Monoclonal antibodies to human laminin alpha4 chain globular domain inhibit tumor
      cell adhesion and migration on laminins 411 and 421, and binding of alpha6beta1
      integrin and MCAM to alpha4-laminins.
AB  - alpha4-Laminins, such as laminins 411 and 421, are mesenchymal laminins expressed
      by vascular and lymphatic endothelial cells, leukocytes and other normal cell
      types. These laminins are recognized by alpha6beta1 and alpha6beta4 integrins and
      MCAM (CD146), and promote adhesion and migration of the cells. alpha4-Laminins
      are also expressed and secreted by some tumor cells and strongly promote tumor
      cell migration. Moreover, the abluminal side of blood and/or lymphatic vessels
      and the nerve perineurium, common tracks of tumor cell dissemination, express
      alpha4-laminins, and these laminin isoforms, when expressed in the stroma, may
      contribute to tumor invasion. In the present study, we examined ten mAbs to human
      laminin alpha4 chain for their reactivity with the isolated laminin alpha4
      globular domain, their ability to inhibit tumor cell adhesion and migration on
      laminins 411 and 421, and their effect on the binding of alpha6beta1 integrin and
      MCAM to both alpha4-laminins. Most of the mAbs reacted with the laminin alpha4
      globular domain, but only two, mAbs FC10 and 084, significantly inhibited tumor
      cell adhesion and migration on laminin-411. When used in combination, these
      antibodies practically abolished the cell adhesion and migration on laminin-411
      and significantly reduced the cellular responses on laminin-421. Accordingly,
      mAbs FC10 and 084 significantly inhibited the binding of purified alpha6beta1
      integrin and MCAM to laminins 411 and 421. These results indicate that mAbs to
      the laminin alpha4 globular domain are able to inhibit tumor cell adhesion and
      migration on laminins 411 and 421, and that alpha6beta1 integrin and MCAM bind
      alpha4-laminins at very close sites on the globular domain. These reagents
      contribute to a better understanding of the biology of alpha4-laminins and may
      have a therapeutic potential in malignant and inflammatory diseases. 

PMID- 24681328
TI  - Neither serotonin nor adenosine-dependent mechanisms preserve ventilatory
      capacity in ALS rats.
AB  - In rats over-expressing SOD1G93A, ventilation is preserved despite significant
      loss of respiratory motor neurons. Thus, unknown forms of compensatory
      respiratory plasticity may offset respiratory motor neuron cell death. Although
      mechanisms of such compensation are unknown, other models of respiratory motor
      plasticity may provide a conceptual guide. Multiple cellular mechanisms give rise
      to phrenic motor facilitation; one mechanism requires spinal serotonin receptor
      and NADPH oxidase activity whereas another requires spinal adenosine receptor
      activation. Here, we studied whether these mechanisms contribute to compensatory
      respiratory plasticity in SOD1G93A rats. Using plethysmography, we assessed
      ventilation in end-stage SOD1G93A rats after: (1) serotonin depletion with
      parachlorophenylalanine (PCPA), (2) serotonin (methysergide) and A2A (MSX-3)
      receptor inhibition, (3) NADPH oxidase inhibition (apocynin), and (4) combined
      treatments. The ability to increase ventilation was not decreased by individual
      or combined treatments; thus, these mechanisms do not maintain breathing capacity
      at end-stage motor neuron disease. Possible mechanisms giving rise to enhanced
      breathing capacity with combined treatment in end-stage SOD1G93A rats are
      discussed.

PMID- 24681329
TI  - Immunomodulatory intervention with interferon-gamma in Escherichia coli
      pyelonephritis.
AB  - PURPOSE: We investigated the efficacy of recombinant human interferon-gamma in
      experimental pyelonephritis due to Escherichia coli. MATERIALS AND METHODS:
      Pyelonephritis was induced by intrapelvic inoculation of bacteria after ureteral
      ligation in 38 rabbits assigned to 1 of 3 groups, including group 1-16 controls,
      group 2-14 rabbits treated with intravenous recombinant human interferon-gamma
      and group 3-8 rabbits treated with intravenous recombinant human interferon-gamma
      plus amikacin. Bacterial counts, cytokines and malondialdehyde were measured in
      blood. Peripheral blood mononuclear cells were isolated to measure TNFalpha
      transcripts, cytokine stimulation and apoptosis. Survival was recorded, and the
      tissue bacterial load and myeloperoxidase activity were measured after sacrifice.
      RESULTS: The mortality rate in groups 1, 2 and 3 was 66.7%, 25% and 12.5%,
      respectively. The circulating bacterial count and tissue bacterial load were less
      in group 2 than in group 1. Circulating malondialdehyde negatively correlated
      with the bacterial load of the spleen. Although the number of TNFalpha
      transcripts in circulating peripheral blood mononuclear cells did not differ,
      peripheral blood mononuclear cells isolated from group 2 at 48 hours produced
      much greater concentrations of tumor necrosis factor-alpha after stimulation with
      Pam3Cys. In parallel, the apoptosis rate of circulating monocytes was increased
      in group 2 at 48 hours. Lung myeloperoxidase activity at 24 hours, serving as
      indirect evidence of neutrophil infiltration, was decreased in group 2.
      CONCLUSIONS: Recombinant human interferon-gamma administration prolonged survival
      in rabbits with experimental E. coli urosepsis. Its action was probably related
      to increased bacterial phagocytosis after modulation of oxidant status and
      reversal of monocyte immunoparalysis.

PMID- 24681330
TI  - Tissue engineered cystoplasty augmentation for treatment of neurogenic bladder
      using small intestinal submucosa: an exploratory study.
AB  - PURPOSE: Bladder augmentation with enterocystoplasty is the gold standard therapy
      for neurogenic bladder. The presence of gastrointestinal segments in the urinary
      tract has been associated with many complications. We investigated an alternative
      approach using small intestinal submucosa as scaffold for reconstruction.
      MATERIALS AND METHODS: We selected 8 candidates with poor bladder capacity and
      compliance for small intestinal submucosa cystoplasty. Candidate age ranged from
      14 to 54 years, and included 6 patients with myelomeningoceles and 2 patients
      with spinal cord injuries. Serial urodynamics, cystograms, ultrasonography and
      serum analyses were used to assess the outcomes of surgery. RESULTS: Followup
      range was 11 to 36 months (mean 12). Compared to the preoperative findings there
      were significant increases in maximum bladder capacity (p<0.05) at the 3 and 12
      month followup (170.1+/-75.7 ml preoperatively, 365.6+/-68.71 ml at 3 months and
      385.5+/-52.8 ml at 12 months), an increase in bladder compliance (p<0.01) at the
      12-month followup (5.9+/-4.0 ml/cm H2O preoperatively and 36.3+/-30.0 ml/cm H2O
      at 12 months) and a decrease in maximum detrusor pressure (p<0.05) at the 12
      month followup (43.6+/-35.7 cm H2O preoperatively and 15.1+/-7.6 cm H2O at 12
      months). Bowel function returned promptly after surgery. No metabolic
      consequences were noted and no urinary calculi were observed. Renal function was
      preserved. CONCLUSIONS: Small intestinal submucosa can be used as a scaffold for
      rebuilding a functional bladder. Tissue engineering technology provides a
      potentially viable option for genitourinary reconstruction in patients with
      neurogenic bladder.

PMID- 24681332
TI  - Adherence to performance measures and outcomes among men treated for prostate
      cancer.
AB  - PURPOSE: We assessed the relationship between health care system performance on
      nationally endorsed prostate cancer quality of care measures and prostate cancer
      treatment outcomes. MATERIALS AND METHODS: This retrospective cohort study
      included 48,050 men from SEER-Medicare linked data diagnosed with localized
      prostate cancer between 2004 and 2009, and followed through 2010. Based on a
      composite quality measure we categorized the health care systems in which these
      men were treated into 1-star (bottom 20%), 2-star (middle 60%) and 3-star (top
      20%) systems. We then examined the association of health care system level
      quality of care with outcomes using multivariable logistic and Cox regression.
      RESULTS: Patients who underwent prostatectomy in 3-star vs 1-star health care
      systems were at lower risk for perioperative complications (OR 0.80, 95% CI 0.64
      1.00). However, they were more likely to undergo a procedure addressing treatment
      related morbidity, eg for sexual morbidity (11.3% vs 7.8%, p = 0.043). In
      patients who received radiotherapy star ranking was not associated with treatment
      related morbidity. In all patients star ranking was not significantly associated
      with all-cause mortality (HR 0.99, 95% CI 0.84-1.15) or secondary cancer therapy
      (HR 1.04, 95% CI 0.91-1.20). CONCLUSIONS: We found no consistent association
      between health care system quality and outcomes, which questions how meaningful
      these measures ultimately are for patients. Thus, future studies should focus on
      developing more discriminative quality measures.

PMID- 24681331
TI  - Alterations in resting state oscillations and connectivity in sensory and motor
      networks in women with interstitial cystitis/painful bladder syndrome.
AB  - PURPOSE: The pathophysiology of interstitial cystitis/painful bladder syndrome
      remains incompletely understood but is thought to involve central disturbance in
      the processing of pain and viscerosensory signals. We identified differences in
      brain activity and connectivity between female patients with interstitial
      cystitis/painful bladder syndrome and healthy controls to advance clinical
      phenotyping and treatment efforts for interstitial cystitis/painful bladder
      syndrome. MATERIALS AND METHODS: We examined oscillation dynamics of intrinsic
      brain activity in a large sample of well phenotyped female patients with
      interstitial cystitis/painful bladder syndrome and female healthy controls. Data
      were collected during 10-minute resting functional magnetic resonance imaging as
      part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain
      Research Network project. The blood oxygen level dependent signal was transformed
      to the frequency domain. Relative power was calculated for multiple frequency
      bands. RESULTS: Results demonstrated altered frequency distributions in
      viscerosensory (post insula), somatosensory (postcentral gyrus) and motor regions
      (anterior paracentral lobule, and medial and ventral supplementary motor areas)
      in patients with interstitial cystitis/painful bladder syndrome. Also, the
      anterior paracentral lobule, and medial and ventral supplementary motor areas
      showed increased functional connectivity to the midbrain (red nucleus) and
      cerebellum. This increased functional connectivity was greatest in patients who
      reported pain during bladder filling. CONCLUSIONS: Findings suggest that women
      with interstitial cystitis/painful bladder syndrome have a sensorimotor component
      to the pathological condition involving an alteration in intrinsic oscillations
      and connectivity in a cortico-cerebellar network previously associated with
      bladder function.

PMID- 24681333
TI  - Defining and treating the spectrum of intermediate risk nonmuscle invasive
      bladder cancer.
AB  - PURPOSE: Low, intermediate and high risk categories have been defined to help
      guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1,
      CIS). However, while low and high risk disease has been well classified, the
      intermediate risk category has traditionally comprised a heterogeneous group that
      does not fit into either of these categories. As a result, many urologists remain
      uncertain about the categorization of patients as intermediate risk as well as
      the selection of the most appropriate therapeutic option for this patient
      population. We review the current literature and clinical practice guidelines on
      intermediate risk nonmuscle invasive bladder cancer and, based on our findings,
      provide urologists with a better understanding of this heterogeneous risk group
      as well as practical recommendations for the treatment of intermediate risk
      patients. MATERIALS AND METHODS: The IBCG analyzed published clinical trials,
      meta-analyses and current clinical practice guidelines on intermediate risk
      nonmuscle invasive bladder cancer available as of September 2013. The definitions
      of intermediate risk, patient outcomes and guideline recommendations were
      considered, as were the limitations of the available literature and additional
      parameters that may be useful in guiding treatment decisions in intermediate risk
      patients. RESULTS: Current definitions and management recommendations for
      intermediate risk nonmuscle invasive bladder cancer vary. The most simple and
      practical definition is that proposed by the IBCG and the AUA of multiple and/or
      recurrent low grade Ta tumors. The IBCG suggests that several factors should be
      considered in clinical decisions in intermediate risk disease, including number
      (greater than 1) and size (greater than 3 cm) of tumors, timing (recurrence
      within 1 year) and frequency (more than 1 per year) of recurrence, and previous
      treatment. In patients without these risk factors a single, immediate
      instillation of chemotherapy is advised. In those with 1 to 2 risk factors
      adjuvant intravesical therapy (intravesical chemotherapy or maintenance bacillus
      Calmette-Guerin) is recommended, and previous intravesical therapy should be
      considered when choosing between these adjuvant therapies. For those patients
      with 3 to 4 risk factors, maintenance bacillus Calmette-Guerin is recommended. It
      is also important that all intermediate risk patients are accurately risk
      stratified at initial diagnosis and during subsequent followup. This requires
      appropriate transurethral resection of the bladder tumor, vigilance to rule out
      carcinoma in situ or other potential high risk tumors, and review of histological
      material directly with the pathologist. CONCLUSIONS: Intermediate risk disease is
      a heterogeneous category, and there is a paucity of independent studies comparing
      therapies and outcomes in subgroups of intermediate risk patients. The IBCG has
      proposed a management algorithm that considers tumor characteristics, timing and
      frequency of recurrence, and previous treatment. Subgroup analyses of
      intermediate risk subjects in pivotal EORTC trials and meta-analyses will be
      important to validate the proposed algorithm and support clear evidence-based
      recommendations for subgroups of intermediate risk patients.

PMID- 24681334
TI  - 2,4-Dialkyl-8,9,10,11-tetrahydrobenzo[g]pyrimido[4,5-c]isoquinoline
      1,3,7,12(2H,4H)-tetraones as new leads against Mycobacterium tuberculosis.
AB  - Given the re-emergence of tuberculosis in Europe and beyond, the search for novel
      bio-active compound classes against this disease is of utmost importance. As a
      result of a high intrinsic tolerance of the etiological agent, Mycobacterium
      tuberculosis, towards most antibiotics and xenobiotics, the search for such new
      compounds is far from trivial. Further exacerbated by the rapid generation and
      spread of drug resistant M. tuberculosis and fuelled by the HIV/AIDS pandemic,
      halting the tuberculosis epidemic is of paramount importance. As part of our
      program to design new 2-aza-anthraquinones with anti-mycobacterial activity,
      various dialkyltetrahydrobenzo[g]pyrimido[4,5-c]isoquinolinetetraones were
      designed and synthesised. The compounds were submitted to a biological evaluation
      in which the activity against M.tb H37Rv(lux) was observed, as well as the acute
      toxicity towards J774 A.1 macrophages. From these results, the selectivity index
      was calculated. Furthermore, the activity of the most promising compounds was
      further studied against a multi-drug resistant LAM-1 strain and against
      intracellular replicating M.tb. The study was further extended with a comet assay
      and a VITOTOXTM assay to investigate the possibility of observable genotoxic
      effects caused by these compounds. 

PMID- 24681336
TI  - Kinetics and mechanism of auto- and copper-catalyzed oxidation of 1,4
      naphthohydroquinone.
AB  - Although quinones represent a class of organic compounds that may exert toxic
      effects both in vitro and in vivo, the molecular mechanisms involved in quinone
      species toxicity are still largely unknown, especially in the presence of
      transition metals, which may both induce the transformation of the various
      quinone species and result in generation of harmful reactive oxygen species. In
      this study, the oxidation of 1,4-naphthohydroquinone (NH2Q) in the absence and
      presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH
      range of 6.5-7.5 has been investigated, with detailed kinetic models developed to
      describe the predominant mechanisms operative in these systems. In the absence of
      copper, the apparent oxidation rate of NH2Q increased with increasing pH and
      initial NH2Q concentration, with concomitant oxygen consumption and peroxide
      generation. The doubly dissociated species, NQ(2-), has been shown to be the
      reactive species with regard to the one-electron oxidation by O2 and
      comproportionation with the quinone species, both generating the semiquinone
      radical (NSQ(.-)). The oxidation of NSQ(.-) by O2 is shown to be the most
      important pathway for superoxide (O2(.-)) generation with a high intrinsic rate
      constant of 1.0*10(8)M(-1)s(-1). Both NSQ(.-) and O2(.-) served as chain
      propagating species in the autoxidation of NH2Q. Cu(II) is capable of catalyzing
      the oxidation of NH2Q in the presence of O2 with the oxidation also accelerated
      by increasing the pH. Both the uncharged (NH2Q(0)) and the mono-anionic (NHQ(-))
      species were found to be the kinetically active forms, reducing Cu(II) with an
      intrinsic rate constant of 4.0*10(4) and 1.2*10(7)M(-1)s(-1), respectively. The
      presence of O2 facilitated the catalytic role of Cu(II) by rapidly regenerating
      Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ(.-)
      resulting in the generation of O2(.-). The half-cell reduction potentials of
      various redox couples at neutral pH indicated good agreement between
      thermodynamic and kinetic considerations for various key reactions involved,
      further validating the proposed mechanisms involved in both the autoxidation and
      the copper-catalyzed oxidation of NH2Q in circumneutral pH solutions.

PMID- 24681335
TI  - 8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase
      activation and alpha-smooth muscle actin polymerization.
AB  - Reactive oxygen species (ROS) are activators of cell signaling and modify
      cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of
      the prominent lesions in oxidatively damaged DNA, whose accumulation is causally
      linked to various diseases and aging processes, whereas its etiological relevance
      is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)
      initiated DNA base excision repair (BER) pathway. OGG1 binds free 8-oxoG and this
      complex functions as an activator of Ras family GTPases. Here we examined whether
      OGG1-initiated BER is associated with the activation of Rho GTPase and mediates
      changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated
      BER in cultured cells and mouse lungs and used molecular approaches such as
      active Rho pull-down assays, siRNA ablation of gene expression, immune blotting,
      and microscopic imaging. We found that OGG1 physically interacts with Rho GTPase
      and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells
      and lungs, which mediates alpha-smooth muscle actin (alpha-SMA) polymerization
      into stress fibers and increases the level of alpha-SMA in insoluble
      cellular/tissue fractions. These changes were absent in cells lacking OGG1. These
      unexpected data and those showing that 8-oxoG repair is a lifetime process
      suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes
      and organ remodeling observed in various chronic diseases. 

PMID- 24681337
TI  - Cooperative interaction of benzo[a]pyrene and ethanol on plasma membrane
      remodeling is responsible for enhanced oxidative stress and cell death in primary
      rat hepatocytes.
AB  - Several epidemiologic studies have shown an interactive effect of heavy smoking
      and heavy alcohol drinking on the development of hepatocellular carcinoma. It has
      also been recently described that chronic hepatocyte death can trigger excessive
      compensatory proliferation resulting later in the formation of tumors in mouse
      liver. As we previously demonstrated that both benzo[a]pyrene (B[a]P), an
      environmental agent found in cigarette smoke, and ethanol possess similar
      targets, especially oxidative stress, to trigger death of liver cells, we decided
      to study here the cellular and molecular mechanisms of the effects of
      B[a]P/ethanol coexposure on cell death. After an 18-h incubation with 100nM
      B[a]P, primary rat hepatocytes were supplemented with 50mM ethanol for 5 or 8h.
      B[a]P/ethanol coexposure led to a greater apoptotic cell death that could be
      linked to an increase in lipid peroxidation. Plasma membrane remodeling, as
      depicted by membrane fluidity elevation and physicochemical alterations in lipid
      rafts, appeared to play a key role, because both toxicants acted with specific
      complementary effects. Membrane remodeling was shown to induce an accumulation of
      lysosomes leading to an important increase in low-molecular-weight iron cellular
      content. Finally, ethanol metabolism, but not that of B[a]P, by providing
      reactive oxygen species, induced the ultimate toxic process. Indeed, in
      lysosomes, ethanol promoted the Fenton reaction, lipid peroxidation, and membrane
      permeabilization, thereby triggering cell death. To conclude, B[a]P exposure, by
      depleting hepatocyte membrane cholesterol content, would constitute a favorable
      ground for a later toxic insult such as ethanol intoxication. Membrane
      stabilization of both plasma membrane and lysosomes might be a potential target
      for further investigation considering cytoprotective strategies. 

PMID- 24681338
TI  - Proteasome activation delays aging in vitro and in vivo.
AB  - Aging is a natural biological process that is characterized by a progressive
      accumulation of macromolecular damage. In the proteome, aging is accompanied by
      decreased protein homeostasis and function of the major cellular proteolytic
      systems, leading to the accumulation of unfolded, misfolded, or aggregated
      proteins. In particular, the proteasome is responsible for the removal of normal
      as well as damaged or misfolded proteins. Extensive work during the past several
      years has clearly demonstrated that proteasome activation by either genetic means
      or use of compounds significantly retards aging. Importantly, this represents a
      common feature across evolution, thereby suggesting proteasome activation to be
      an evolutionarily conserved mechanism of aging and longevity regulation. This
      review article reports on the means of function of these proteasome activators
      and how they regulate aging in various species. 

PMID- 24681339
TI  - Chaperone-like activity of monomeric human 14-3-3zeta on different protein
      substrates.
AB  - Members of the 14-3-3 protein family interact with hundreds of different,
      predominantly phosphorylated, proteins. 14-3-3 dimers are prevalent but exist at
      the equilibrium with the monomers. Our previous studies using the engineered
      monomeric 14-3-3zeta (14-3-3zetam) showed that 14-3-3zeta monomer retained
      binding activity towards selected phosphorylated partners and, in addition, it
      prevented heat-induced aggregation of myosin subfragment 1. Since the chaperone
      like activity of 14-3-3 monomers has been insufficiently studied, here we have
      analyzed the effect of 14-3-3zetam on the aggregation of different model
      proteins. We found that 14-3-3zetam demonstrated considerable chaperone-like
      activity by inhibiting the DTT-induced aggregation of insulin and thermally
      induced aggregation of alcohol dehydrogenase and phosphorylase kinase.
      Importantly, the anti-aggregating activity of 14-3-3zetam was concentration
      dependent and overall, was more pronounced than that of its dimeric counterpart.
      In some cases, the chaperone-like effect of 14-3-3zetam was comparable, or even
      higher, than that of the small heat shock proteins, HspB6 and HspB5. We suggest
      that 14-3-3s not only can bind and regulate the activity of multiple
      phosphoproteins, but also possess moonlighting chaperone-like activity, which is
      especially pronounced in the case of monomeric forms of 14-3-3 which can be
      present under certain stress conditions. 

PMID- 24681340
TI  - Pyrolysis based bio-refinery for the production of bioethanol from demineralized
      ligno-cellulosic biomass.
AB  - This paper evaluates a novel biorefinery approach for the conversion of
      lignocellulosic biomass from pinewood. A combination of thermochemical and
      biochemical conversion was chosen with the main product being ethanol. Fast
      pyrolysis of lignocellulosic biomasss with fractional condensation of the
      products was used as the thermochemical process to obtain a pyrolysis-oil rich in
      anhydro-sugars (levoglucosan) and low in inhibitors. After hydrolysis of these
      anhydro-sugars, glucose was obtained which was successfully fermented, after
      detoxification, to obtain bioethanol. Ethanol yields comparable to traditional
      biochemical processing were achieved (41.3% of theoretical yield based on
      cellulose fraction). Additional benefits of the proposed biorefinery concept
      comprise valuable by-products of the thermochemical conversion like bio-char,
      mono-phenols (production of BTX) and pyrolytic lignin as a source of aromatic
      rich fuel additive. The inhibitory effect of thermochemically derived
      fermentation substrates was quantified numerically to compare the effects of
      different process configurations and upgrading steps within the biorefinery
      approach. 

PMID- 24681341
TI  - Prednisolone increases enterohepatic cycling of bile acids by induction of Asbt
      and promotes reverse cholesterol transport.
AB  - BACKGROUND & AIMS: Glucocorticoids, produced by the adrenal gland under control
      of the hypothalamic-pituitary-adrenal axis, exert their metabolic actions largely
      via activation of the glucocorticoid receptor (GR). Synthetic glucocorticoids are
      widely used as anti-inflammatory and immunosuppressive drugs but their
      application is hampered by adverse metabolic effects. Recently, it has been shown
      that GR may regulate several genes involved in murine bile acid (BA) and
      cholesterol metabolism, yet the physiological relevance hereof is controversial.
      The aim of this study is to provide a mechanistic basis for effects of
      prednisolone on BA and cholesterol homeostasis in mice. METHODS: Male BALB/c mice
      were treated with prednisolone (12.5mg/kg/day) for 7days by subcutaneous
      implantation of slow-release pellets, followed by extensive metabolic profiling.
      RESULTS: Sustained prednisolone treatment induced the expression of the apical
      sodium-dependent bile acid transporter (Asbt) in the ileum, which stimulated BA
      absorption. This resulted in elevated plasma BA levels and enhanced biliary BA
      secretion. Concomitantly, both biliary cholesterol and phospholipid secretion
      rates were increased. Enhanced BA reabsorption suppressed hepatic BA synthesis,
      as evident from hepatic gene expression, reduced plasma C4 levels and reduced
      fecal BA loss. Plasma HDL cholesterol levels were elevated in prednisolone
      treated mice, which likely contributed to the stimulated flux of cholesterol from
      intraperitoneally injected macrophage foam cells into feces. CONCLUSIONS:
      Sustained prednisolone treatment increases enterohepatic recycling of BA, leading
      to elevated plasma levels and reduced synthesis in the absence of cholestasis.
      Under these conditions, prednisolone promotes macrophage-derived reverse
      cholesterol transport.

PMID- 24681343
TI  - FOLFOX-4 vs. doxorubicin for hepatocellular carcinoma: could a negative result be
      accepted as positive?

PMID- 24681342
TI  - Prospective randomized pilot study of Y90+/-sorafenib as bridge to
      transplantation in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: To investigate the safety and adverse event profile of
      sorafenib plus radioembolization (Y90) compared to Y90 alone in patients awaiting
      liver transplantation. METHODS: 20 patients with HCC were randomized to Y90 alone
      (Group A) or Y90+sorafenib (Group B). Adverse events, dose reductions, and peri
      transplant complications were assessed. RESULTS: All patients in the sorafenib
      group necessitated dose reductions. Seventeen of 20 patients underwent liver
      transplantation; median time-to-transplant was 7.8 months (range: 4.2-20.3) and
      similar between groups (p = 0.35). In the sorafenib group, there were 4/8 peri
      transplant (<30 days) biliary complications (p = 0.029) and 3/8 acute rejections
      (p = 0.082); there were none in the Y90-only group. Survival rates were 70%
      (Group A) and 72% (Group B) at 3 years (p = 0.57). CONCLUSIONS: The addition of
      sorafenib to Y90 necessitated dose reductions in all patients awaiting
      transplantation. Preliminary data suggest that the combination was associated
      with more peri-transplant biliary complications and potentially trended towards
      more acute rejections. Caution should be exercised when considering sorafenib in
      the transplant setting. Further investigation is warranted.

PMID- 24681344
TI  - Differential regulation of inflammation and apoptosis in Fas-resistant hepatocyte
      specific Bid-deficient mice.
AB  - BACKGROUND & AIMS: Activation of Fas death receptor results in apoptosis in
      multiple organs, particularly liver, in a process dependent on Bid cleavage. Mice
      injected with an anti-Fas antibody die within hours of acute liver failure
      associated with massive apoptosis and hemorrhage. Our aim was to investigate the
      crosstalk of apoptotic and inflammatory pathways and the contribution of
      selective hepatocellular apoptosis during in vivo Fas activation. METHODS: We
      generated hepatocyte-specific Bid deficient mice (hBid(-/-)). Acute liver injury
      was induced by Fas-activating antibody (Jo2) in a time-course study. RESULTS: In
      contrast to controls, nearly all Jo2 injected hBid(-/-) survived. Their livers
      showed complete protection against hepatocellular apoptosis with minimal focal
      hemorrhagic changes and mainly non-parenchymal cell apoptosis. In agreement, the
      hepatocytes had no mitochondrial cytochrome c release in cytosol, or caspase 3
      activation. hBid(-/-) livers showed marked increase in acute inflammatory foci
      composed of neutrophils and monocytes associated with the increased expression of
      proinflammatory chemokines and cytokines, in the manner dependent on non
      canonical interleukin-1beta activation and amplified in the absence of caspase-3
      activation. In addition, hBid(-/-) mice were completely protected from
      hepatotoxicity and the infiltrated cells were cleared 2 weeks post single Jo2
      injection. CONCLUSIONS: Hepatocyte Bid suppression is critical for the resistance
      to the lethal effects of Fas activation in vivo. Fas signaling induces
      differential activation of non-canonical interleukin-1beta maturation, amplified
      in the absence of apoptotic Bid-mitochondrial loop, in hepatocytes. These
      findings may have important pathophysiological and therapeutic implications in a
      variety of liver disorders associated with Fas activation.

PMID- 24681345
TI  - Epidemiology and outcomes of bloodstream infection in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Bloodstream infections (BSIs) in cirrhotic patients are 10
      fold more common than in non-cirrhotic patients and increasingly caused by
      resistant pathogens. We examined 162 BSI episodes in cirrhotic patients to
      describe the etiology and risk factors for 30-day mortality. METHODS: We
      retrospectively analyzed all consecutive BSIs in patients with liver cirrhosis at
      our 1350-bed teaching hospital (January 2008 to June 2012). Cox-proportional
      hazard regression was used to analyze the impact of disease and treatment-related
      variables on the crude 30-day mortality. RESULTS: BSI episodes were identified in
      162 patients, including 29 mixed infections. Most of episodes were classified as
      hospital acquired or healthcare associated (93%). Gram-negative bacteria (GNB),
      Gram-positive bacteria and Candida spp. caused 64%, 38%, and 10% of episodes,
      respectively. GNB were classified as multi-drug resistant (MDR) and extensively
      drug resistant (XDR) in 25% and 21% of cases, respectively. The overall crude 30
      day mortality rate was 29%. Four risk factors were independently associated with
      30-day crude mortality: worsening of MELD score from baseline (the last MELD
      score available in the 2 weeks prior BSI) to that at BSI onset (HR 1.11 per point
      increase, 95% CI 1.07-1.15, p<0.0001), spontaneous bacterial peritonitis as BSI
      source (HR 4.42, 2.04-9.54, p=0.002), sepsis grading (HR 2.18, 1.39-3.43,
      p=0.0007), and inappropriate antibiotic therapy within 24h from blood cultures
      (HR 2.82, 1.50-5.41, p=0.002). CONCLUSION: An increasing proportion of BSIs in
      cirrhotic patients are caused by resistant GNB and Candida spp. Accurate
      evaluation of risk factors for mortality may improve early appropriate
      therapeutic management.

PMID- 24681346
TI  - Serum ferritin predicts early mortality in patients with decompensated cirrhosis.
AB  - BACKGROUND & AIMS: Serum ferritin is a known marker of hepatic necro-inflammation
      and has been studied to predict 1 year mortality and post-transplant survival in
      decompensated cirrhotics. However, there are no studies evaluating ferritin as a
      predictor of early mortality. We investigated whether serum ferritin levels could
      predict 15 day and 30 day mortality in patients with decompensated cirrhosis.
      METHODS: 318 patients with decompensated cirrhosis were included. RESULTS:
      Patients of decompensated cirrhosis [257 males, mean age of 51 [+/-13]years, were
      followed for a median of 31 days. Serum ferritin levels were significantly
      different between survivors and non-survivors [p<0.001] and showed significant
      correlation with MELD score [p<0.001], CTP score [p<0.001], leucocyte counts
      [TLC] [p<0.001], serum sodium [p<0.001], ACLF grades [p=0.005], spontaneous
      bacterial peritonitis [SBP] [p=0.02], hepatic encephalopathy [HE] [p<0.001] and
      hepatorenal syndrome [HRS] [p=0.012]. Serum ferritin, etiology, MELD, HE, CTP
      score, sodium, TLC, and ACLF grades were significant predictors of mortality on
      univariate analysis. Ferritin [p=0.04, HR 1.66 95% CI (1.02-2.73)] was a
      significant predictor of early mortality on multivariate analysis along with HE
      [p=0.006, HR 3.47 95% CI (2.13-8.41)] (Model 1), TLC [p=0.02, HR 1.81 95% CI
      (1.06-3.07)] (Model 2), ACLF grades [p=0.018, HR 2.013,95% CI (1.126-3.60)], and
      CTP score [p<0.0001, HR 1.36 95% CI (1.17-1.59)] (Model 3). CONCLUSION: Serum
      ferritin levels correlate with severity of hepatic decompensation and are
      associated with early liver related death independent of the MELD score in
      hospitalized patients with decompensated cirrhosis. This could also have a
      potential therapeutic implication.

PMID- 24681347
TI  - KCNE2 modulates cardiac L-type Ca(2+) channel.
AB  - KCNE2 plays an important role in maintaining cardiac electrical stability.
      Mutations in KCNE2 have been linked to long-QT syndrome (LQT6) and atrial
      fibrillation/short QT syndrome. It has been suggested that KCNE2 has the most
      promiscuity of function which can interact with multiple-subunits of voltage
      dependent cation channels and modulate their functions. However, whether KCNE2
      regulates voltage-dependent L-type Ca(2)(+) channel (LCC) remains unknown. This
      study investigated the possible role of KCNE2 in regulating cardiac LCCs and the
      pathophysiological relevance of this regulation. We found that overexpression of
      KCNE2 in Sprague-Dawley rat cardiomyocytes decreased L-type Ca(2+)current
      (ICa,L), whereas KCNE2 knockdown by RNA interference increased ICa,L.
      Upregulation of KCNE2 caused a slight positive shift of the voltage-dependent
      activation and a negative shift of the steady-state voltage-dependent
      inactivation, and slowed the recovery from inactivation of ICa,L, while knockdown
      of KCNE2 had the contrary effects. Similar regulation of ICa,L magnitude had been
      observed in transfected HEK 293 cells. Coimmunoprecipitation and colocalization
      assays in both cardiomyocytes and the transfected cell line suggest that Cav1.2
      physically interacted with KCNE2. Deletion of the N-terminal inhibitory module
      (NTI) of Cav1.2 results in the large loss of KCNE2 regulation of ICa,L and
      interaction with Cav1.2. Furthermore, we found that the familial atrial
      fibrillation related KCNE2 mutation R27C enhanced the effect of KCNE2 on
      suppressing ICa,L. Taken together, our findings indicate that KCNE2 modulates
      ICa,L by regulating NTI function of Cav1.2. The KCNE2 mutation R27C may induce
      familial atrial fibrillation partially through enhancing the suppression of
      ICa,L. 

PMID- 24681348
TI  - Protein quality control, the ubiquitin proteasome system, and autophagy: when
      worlds collide. [Corrected].

PMID- 24681349
TI  - A new technique of bronchial microsampling and proteomic analysis of epithelial
      lining fluid in a rat model of acute lung injury.
AB  - The standard technique to evaluate the proteins present in epithelial lining
      fluid (ELF) is bronchoalveolar lavage (BAL). Bronchoscopic microsampling (BMS)
      method has been developed for humans as a less invasive alternative. We establish
      the usefulness of a rat bronchial microsampling (rBMS) to evaluate various
      proteins in ELF in lipopolysaccharide (LPS)-induced lung injury models in rats.
      In the first experiment of this study, we validate that whether the rBMS can
      obtain information from ELF in place of BAL. Tumor necrosis factor (TNF)-alpha
      concentrations were increased in the rBMS samples similar to BAL 1 and 3h after
      LPS instillation. In the second part of this study, a proteomic analysis of the
      rBMS, using the Protein Chip(R) system, revealed the presence of proteins whose
      molecular weights corresponded to TNF-related proteins in the LPS-treated rats.
      In rats treated with a TNF-alpha converting enzyme inhibitor, the concentrations
      of these proteins in rBMS decreased or disappeared. In the third experiment, rBMS
      was performed without tracheostomy at 6 and 24h after instillation of LPS, and a
      rat multiple cytokines assay system detected heterogeneous variations in the
      concentrations of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, TNF
      alphaand interferon (IFN)-gamma in ELF. The cytokine profile was significantly
      modified by pre-treatment with dexamethasone. This new rBMS technique could be
      used to measure TNF-alpha in LPS-induced acute lung injury (ALI) as well as for
      proteomic analysis, without sacrificing the rats. Furthermore, this procedure
      enables the serial collection of ELF, which would allow the examination of time
      dependent cytokine variations in rat ALI model. 

PMID- 24681350
TI  - Non-neuronal cholinergic airway epithelium biology.
AB  - Acetylcholine, a major regulator of airway function, is not solely produced by
      neurons but also by a variety of non-neurons cells including various airway
      epithelial cells utilizing a molecular machinery of acetylcholine synthesis and
      release that differs from that of neurons. While canonical neuronal cholinergic
      signaling pathways, for example, nerve driven bronchoconstriction, are still
      valid, new pathways of cholinergic communication have emerged which center around
      innate immunity. These include cholinergic luminal signaling via the airway
      lining fluid to reach receptors at the apical side of epithelial cells and on
      macrophages patrolling on the surface, and preneuronal cholinergic signaling
      where sensory neurons are the target of ACh released from a recently identified
      chemosensory cell that monitors the airway lining fluid for the presence of
      potentially hazardous compounds utilizing the classical taste transduction
      cascade. 

PMID- 24681351
TI  - Ligand bias prevents class equality among beta-blockers.
AB  - beta-Blockers are used for a wide range of diseases from hypertension to
      glaucoma. In some diseases/conditions all beta-blockers are effective, while in
      others only certain subgroups are therapeutically beneficial. The best-documented
      example for only a subset of beta-blockers showing clinical efficacy is in heart
      failure, where members of the class have ranged from completely ineffective, to
      drugs of choice for treating the disease. Similarly, beta-blockers were tested in
      murine asthma models and two pilot clinical studies. A different subset was found
      to be effective for this clinical indication. These findings call into question
      the current system of classifying these drugs. To consider 'beta-blockers', as a
      single class is misleading when considering their rigorous pharmacological
      definition and their appropriate clinical application. 

PMID- 24681352
TI  - Mir-23b and miR-130b expression is downregulated in pituitary adenomas.
AB  - MicroRNA (miRNA) deregulation plays a critical role in tumorigenesis. miR-23b and
      miR-130b are induced by thyrotropin in thyroid cells in a cAMP-dependent manner.
      The aim of our work has been to investigate the possible role of miR-23b and miR
      130b in pituitary tumorigenesis. We have analyzed their expression in a panel of
      pituitary adenomas (PAs) including GH and NFPA adenomas. We report that miR-23b
      and miR-130b are drastically reduced in GH, gonadotroph and NFPA adenomas in
      comparison with normal pituitary gland. Interestingly, the overexpression of miR
      23b and miR-130b inhibits cell proliferation arresting the cells in the G1 and G2
      phase of the cell cycle, respectively. Moreover, we demonstrate that miR-23b and
      miR-130b target HMGA2 and cyclin A2 (CCNA2) genes, respectively. Finally,
      downregulation of miR-23b and miR-130b expression is associated with increased
      levels of their respective targets in human PAs. These findings suggest that miR
      23b and miR-130b downregulation may contribute to pituitary tumorigenesis.

PMID- 24681353
TI  - Modulation of response patterns in human auditory cortex during a target
      detection task: an intracranial electrophysiology study.
AB  - Selective attention enhances cortical activity representing an attended sound
      stream in human posterolateral superior temporal gyrus (PLST). It is unclear,
      however, what mechanisms are associated with a target detection task that
      necessitates sustained attention (vigilance) to a sound stream. We compared
      responses elicited by target and non-target sounds, and to sounds presented in a
      passive-listening paradigm. Subjects were neurosurgical patients undergoing
      invasive monitoring for medically refractory epilepsy. Stimuli were complex
      tones, band-limited noise bursts and speech syllables. High gamma cortical
      activity (70-150 Hz) was examined in all subjects using subdural grid electrodes
      implanted over PLST. Additionally, responses were measured from depth electrodes
      implanted within Heschl's gyrus (HG) in one subject. Responses to target sounds
      recorded from PLST were increased when compared to responses elicited by the same
      sounds when they were not-targets, and when they were presented during passive
      listening. Increases in high gamma activity to target sounds occurred during
      later portions (after 250 ms) of the response. These increases were related to
      the task and not to detailed stimulus characteristics. In contrast, earlier
      activity that did not vary across conditions did represent stimulus acoustic
      characteristics. Effects observed on PLST were not noted in HG. No consistent
      effects were noted in the averaged evoked potentials in either cortical region.
      We conclude that task dependence modulates later activity in PLST during
      vigilance. Later activity may represent feedback from higher cortical areas.
      Study of concurrently recorded activity from frontoparietal areas is necessary to
      further clarify task-related modulation of activity on PLST.

PMID- 24681355
TI  - Age-related changes in prefrontal activity during walking in dual-task
      situations: a fNIRS study.
AB  - BACKGROUND: Previous studies suggest that the human gait is under control of
      higher-order cognitive processes, located in the frontal lobes, such that an age
      related degradation of cognitive capabilities has a negative impact on gait.
      METHODS: Using functional Near-Infrared-Spectroscopy (fNIRS) we investigate the
      frontocortical hemodynamic correlates of dual-task walking in two conditions. 15
      young and 10 older individuals walked on a treadmill while completing concurrent
      tasks that had either visual (checking) or verbal-memory (alphabet recall)
      demands. We compared subjects' motor performance, as well as their prefrontal
      activity in single- and dual-task walking. RESULTS: Our behavioral data partly
      confirm previous accounts on higher dual-task costs in stepping parameters (i.e.,
      decreased step duration) in old age, particularly with a visual task and negative
      dual-task cost (i.e., improved performance) during the verbal task in young
      adults. Functional imaging data revealed little change of prefrontal activation
      from single- to dual-task walking in young individuals. In the elderly, however,
      prefrontal activation substantially decreased during dual-task walking with a
      complex visual task. CONCLUSION: We interpret these findings as evidence for a
      shift of processing resources from the prefrontal cortex to other brain regions
      when seniors face the challenge of walking and concurrently executing a visually
      demanding task.

PMID- 24681354
TI  - Neural correlates of auditory scene analysis and perception.
AB  - The auditory system is designed to transform acoustic information from low-level
      sensory representations into perceptual representations. These perceptual
      representations are the computational result of the auditory system's ability to
      group and segregate spectral, spatial and temporal regularities in the acoustic
      environment into stable perceptual units (i.e., sounds or auditory objects).
      Current evidence suggests that the cortex-specifically, the ventral auditory
      pathway-is responsible for the computations most closely related to perceptual
      representations. Here, we discuss how the transformations along the ventral
      auditory pathway relate to auditory percepts, with special attention paid to the
      processing of vocalizations and categorization, and explore recent models of how
      these areas may carry out these computations. 

PMID- 24681356
TI  - Secretion of interleukin-17 by CD8+ T cells expressing CD146 (MCAM).
AB  - Interleukin-17 (IL-17) has been associated with the pathogenesis of numerous
      autoimmune diseases. CD4+ T cells secreting IL-17 are termed Th17 cells. CD8+ T
      cells, designated Tc17 cells, are also capable of secreting IL-17. Here we
      describe a population of Tc17 cells characterized by the expression of surface
      CD146, an endothelial adhesion molecule. These cells display signatures of a
      human Tc17 genotype and phenotype. Circulating CD8+CD146+ T cells are present in
      low levels in healthy adults. Elevations in CD8+CD146+ T cells are found in
      Behcet's disease and birdshot retinochoroidopathy, which have been reported to
      have HLA class I associations. Sarcoidosis does not have a class I association
      and displays an increase in CD4+ CD146+ T cells but not in CD8+CD146+ T cells.
      CD146 on these cells may facilitate their ability to bind to, and migrate
      through, endothelium, as has been reported for CD4+CD146+ T cells.

PMID- 24681357
TI  - Transcriptomic study of 39 ostreid herpesvirus 1 genes during an experimental
      infection.
AB  - Massive mortality outbreaks have been reported in France since 2008 among Pacific
      oysters, Crassostrea gigas, with the detection of a particular OsHV-1 variant
      called MUVar. Virus infection can be induced in healthy spat in experimental
      conditions allowing to better understand the disease process, including viral
      gene expression. Although gene expression of other herpesviruses has been widely
      studied, we provide the first study following viral gene expression of OsHV-1
      over time. In this context, an in vivo transcriptomic study targeting 39 OsHV-1
      genes was carried out during an experimental infection of Pacific oyster spat.
      For the first time, several OsHV-1 mRNAs were detected by real-time PCR at 0 h, 2
      h, 4 h, 18 h, 26 h and 42 h post-injection. Several transcripts were detected at
      2h post-infection and at 18 h post-infection for all selected ORFs.
      Quantification of virus gene expression at different times of infection was also
      carried out using an oyster housekeeping gene, Elongation factor. Developing an
      OsHV-1-specific reverse transcriptase real time PCR targeting 39 viral gene
      appears a new tool in terms of diagnosis and can be used to complement viral DNA
      detection in order to monitor viral replication.

PMID- 24681358
TI  - Establishment of fungal entomopathogens Beauveria bassiana and Bionectria
      ochroleuca (Ascomycota: Hypocreales) as endophytes on artichoke Cynara scolymus.
AB  - Entomopathogenic fungi (EPF) are commonly found in diverse habitats and are known
      to cause mycoses in many different taxa of arthropods. Various unexpected roles
      have been recently reported for fungal entomopathogens, including their presence
      as fungal endophytes, plant disease antagonists, rhizosphere colonizers and plant
      growth promoting fungi. In Tunisia, a wide range of indigenous EPF isolates from
      different species, such as Beauveria bassiana and Bionectria ochroleuca, were
      found to occur in the soil, and to be pathogenic against the artichoke aphid
      Capitophorus elaeagni (Hemiptera: Aphididae). Since endophytic fungi are recently
      regarded as plant-defending mutualists and their presence in internal plant
      tissue has been discussed as an adaptive protection against insects, we were
      interested on elucidating the possible endophytic behavior of B. bassiana and B.
      ochroleuca on artichoke, Cynara scolymus, after foliar spraying tehcnique. The
      leaf spray inoculation method was effective in introducing the inoculated fungi
      into the plant tissues and showed, then, an endophytic activity on artichoke even
      10 days later. According S-N-K test, there was significant differences between
      the two fungal treatments, B. ochroleuca (84% a) and B. bassiana (78% a), and
      controls (0% b). Likewise, the inoculated entomopathogenic fungi were also
      isolated from new leaves even though with significant differences respectively
      between controls (0% c), B. bassiana (56% b) and B. ochroleuca (78% a). These
      results reveals significant new data on the interaction of inoculated fungi with
      artichoke plant as ecological roles that can be exploited for the protection of
      plants.

PMID- 24681359
TI  - Assessment of WSSV prevalence and distribution of disease-resistant shrimp among
      the wild population of Penaeus monodon along the west coast of India.
AB  - Shrimp aquaculture is threatened by many diseases, among which white spot disease
      (WSD) caused by white spot syndrome virus (WSSV) is the leading one. Information
      related to the geographical distribution and seasonal prevalence of WSD is
      necessary to obtain a clear understanding of the disease biology in shrimp.
      Identification of WSD-resistant individual shrimp with DNA markers is also an
      important technique to develop better WSD-free shrimp health management. The
      present study aim is to estimate the occurrence of WSSV in Penaeus monodon
      qualitatively and quantitatively during three different seasons during the years
      2011 to 2013 along the west coast of India. Additionally, the disease resistance
      prevalence using previously developed 71 bp microsatellite and 457 bp RAPD-SCAR
      DNA markers is also investigated. Samples were collected throughout the year from
      four locations along the west coast of India: Kochi, Kerala; Mangalore,
      Karnataka; Vasco-da-Gama, Goa; and Veraval, Gujarat. The results depicted that
      the average WSSV prevalence, as determined by the nested PCR method and taken
      cumulatively over the four locations, was the lowest (0%) during the post-monsoon
      season and the highest (31.6%) during the monsoon season. The WSD prevalence was
      observed to increase when the latitude was decreased along the west coast of
      India (from Veraval to Kochi). Out of the three different seasons, the average
      WSSV copy number was the highest (approximately 10(3) copies MUg(-1) shrimp
      genomic DNA) during the monsoon season. The disease-resistant prevalence, as
      determined using the developed DNA markers, was found to be the highest in Vasco
      da-Gama (59.5%) and the lowest in Kochi (40.9%). The present study suggests
      better options for the efficient collection of disease-free and disease-resistant
      brood stocks, which would be a more cost-effective and safer approach toward
      disease prevention over conventional trends of seed generation from unselected
      wild brood stock.

PMID- 24681360
TI  - Influence of amendments and aided phytostabilization on metal availability and
      mobility in Pb/Zn mine tailings.
AB  - A greenhouse experiment was conducted to evaluate the effect of four different
      amendments, bone mill, bottom ash, furnace slag, and red mud, as immobilizing
      agents and the plant species Miscanthus sinensis and Pteridium aquilinum in aided
      phytostabilization of Pb/Zn mine tailings. The effects of amendments and plants
      on the availability and mobility of heavy metals were evaluated using single
      extraction, sequential extraction, pore-water analysis, and determination of
      heavy metal concentrations in plants. The application of Fe-rich amendments
      significantly reduced the amount of soluble and extractable heavy metals in the
      tailings (p < 0.05). Furnace slag and M. sinensis reduced CaCl2-extractable heavy
      metals by 56-91%, red mud and P. aquilinum treatment was the most effective at
      decreasing bioaccessible Pb, reducing it to 34% of the total Pb. Compared to
      control, water soluble Cd, Cu, Pb, and Zn were reduced by 99, 99, 98, and 99%,
      respectively, in the red mud and P. aquilinum tailings. M. sinensis accumulated
      heavy metals mainly in the root, and had lower translocation factors compared
      with P. aquilinum. The results of this study suggest that M. sinensis can be used
      in aided phytostabilization for these types of mine tailings and Fe-rich
      amendments are effective for the in situ immobilization of metals. 

PMID- 24681361
TI  - Palm tree mulch as substrate for primary treatment wetlands processing high
      strength urban wastewater.
AB  - The life span of subsurface flow treatment wetlands is determined by the clogging
      of the substrate. Thus, the influent should undergo primary treatment to reduce
      loadings of suspended solids and dissolved organic matter. An-organic based
      substrate should be less prone to clogging because of its remarkably higher
      porosity and plasticity. Mulch obtained from branches of the Canarian palm tree
      (Phoenix canariensis) has been tested as substrate for mixed flow, intermittently
      fed treatment wetland mesocosms processing high strength urban wastewater. The
      effect of the presence of plants (Phragmites and Cyperus), influent pressure and
      hydraulic loading rate was studied. The best removals (SS: 89%, COD: 77%,
      turbidity: 82%) have been obtained with planted reactors treating highly
      concentrated influents at the lower hydraulic loading rates tested. The palm tree
      mulch units achieved similar removals of SS, COD and turbidity to one having
      gravel as substrate and planted with common reed. Mulch obtained from stems of
      giant reed (Arundo donax) provided similar removals of SS and turbidity but that
      of COD was lower. The combination of organic-based TWs with gravel-based ones
      provided high removals (SS: 95%, COD: 78%, turbidity: 95%) while the risk of
      clogging was strongly reduced. 

PMID- 24681362
TI  - Mountain pine beetle infestation of lodgepole pine in areas of water diversion.
AB  - The Rocky Mountains have experienced extensive infestations from the mountain
      pine beetle (Dendroctonus ponderosae Hopkins), affecting numerous pine tree
      species including lodgepole pine (Pinus contorta Dougl. var. latifolia). Water
      diversions throughout the Rocky Mountains transport large volumes of water out of
      the basins of origin, resulting in hydrologic modifications to downstream areas.
      This study examines the hypothesis that lodgepole pine located below water
      diversions exhibit an increased incidence of mountain pine beetle infestation and
      mortality. A ground survey verified diversion structures in a portion of Grand
      County, Colorado, and sampling plots were established around two types of
      diversion structures, canals and dams. Field studies assessed mountain pine
      beetle infestation. Lodgepole pines below diversions show 45.1% higher attack and
      38.5% higher mortality than lodgepole pines above diversions. These findings
      suggest that water diversions are associated with increased infestation and
      mortality of lodgepole pines in the basins of extraction, with implications for
      forest and water allocation management. 

PMID- 24681363
TI  - Metal mobilization under alkaline conditions in ash-covered tailings.
AB  - The aim of this study was to determine element mobilization and accumulation in
      mill tailings under alkaline conditions. The tailings were covered with 50 cm of
      fly ash, and above a sludge layer. The tailings were geochemically and
      mineralogically investigated. Sulfides, such as pyrrhotite, sphalerite and galena
      along with gangue minerals such as dolomite, calcite, micas, chlorite, epidote,
      Mn-pyroxene and rhodonite were identified in the unoxidized tailings. The
      dissolution of the fly ash layer resulted in a high pH (close to 12) in the
      underlying tailings. This, together with the presence of organic matter,
      increased the weathering of the tailings and mobilization of elements in the
      uppermost 47 cm of the tailings. All primary minerals were depleted, except
      quartz and feldspar which were covered by blurry secondary carbonates. Sulfide
      associated elements such as Cd, Fe, Pb, S and Zn and silicate-associated elements
      such as Fe, Mg and Mn were released from the depletion zone and accumulated
      deeper down in the tailings where the pH decreased to circum-neutral. Sequential
      extraction suggests that Cd, Cu, Fe, Pb, S and Zn were retained deeper down in
      the tailings and were mainly associated with the sulfide phase. Calcium, Cr, K
      and Ni released from the ash layer were accumulated in the uppermost depletion
      zone of the tailings. 

PMID- 24681365
TI  - Changing behavior towards sustainable practices using Information Technology.
AB  - This article addresses the question of how to change individuals' behavior
      towards more sustainable practices using Information Technology (IT). By
      following a multidisciplinary and socio-technical perspective, this inquiry is
      answered by applying a new framework-The Commonality Framework for IT-enabled
      Change-on a case study of sustainable behavioral change. The framework is
      grounded in practice theory and is used to analyze the implementation of an IT
      system aimed at changing citizens' behavior towards more sustainable transport
      logistics and procurement in Uppsala, Sweden. The article applies case study
      research design and the empirical data consists of surveys, in-depth and semi
      structured interviews, observations and archival documents. The results show how
      the change towards sustainable practices is an entanglement of both social and
      technical-structural elements across time. In this process, structures such as IT
      are the enablers, and the actors and their social activities are the tipping
      point factors that ultimately determine the success of changing individuals'
      behavior towards a more sustainable direction. This article provides a more
      balanced view of how both actor and structure related properties interact during
      the on-going work with change towards greater sustainability practices than
      earlier research has offered. More specifically, the article offers both a lower
      level theory and a method from which we can analyze change processes where
      technology is seen in its context, and where both technology and the human actor
      is brought forth to center stage. 

PMID- 24681364
TI  - Removal of organic compounds and trace metals from oil sands process-affected
      water using zero valent iron enhanced by petroleum coke.
AB  - The oil production generates large volumes of oil sands process-affected water
      (OSPW), referring to the water that has been in contact with oil sands or
      released from tailings deposits. There are concerns about the environmental
      impacts of the release of OSPW because of its toxicity. Zero valent iron alone
      (ZVI) and in combination with petroleum coke (CZVI) were investigated as
      environmentally friendly treatment processes for the removal of naphthenic acids
      (NAs), acid-extractable fraction (AEF), fluorophore organic compounds, and trace
      metals from OSPW. While the application of 25 g/L ZVI to OSPW resulted in 58.4%
      removal of NAs in the presence of oxygen, the addition of 25 g petroleum coke
      (PC) as an electron conductor enhanced the NAs removal up to 90.9%. The increase
      in ZVI concentration enhanced the removals of NAs, AEF, and fluorophore compounds
      from OSPW. It was suggested that the electrons generated from the oxidation of
      ZVI were transferred to oxygen, resulting in the production of hydroxyl radicals
      and oxidation of NAs. When OSPW was de-oxygenated, the NAs removal decreased to
      17.5% and 65.4% during treatment with ZVI and CZVI, respectively. The removal of
      metals in ZVI samples was similar to that obtained during CZVI treatment.
      Although an increase in ZVI concentration did not enhance the removal of metals,
      their concentrations effectively decreased at all ZVI loadings. The Microtox((r))
      bioassay with Vibrio fischeri showed a decrease in the toxicity of ZVI- and CZVI
      treated OSPW. The results obtained in this study showed that the application of
      ZVI in combination with PC is a promising technology for OSPW treatment. 

PMID- 24681366
TI  - Stormwater quality of spring-summer-fall effluent from three partial-infiltration
      permeable pavement systems and conventional asphalt pavement.
AB  - This study examined the spring, summer and fall water quality performance of
      three partial-infiltration permeable pavement (PP) systems and a conventional
      asphalt pavement in Ontario. The study, conducted between 2010 and 2012, compared
      the water quality of effluent from two Interlocking Permeable Concrete Pavements
      (AquaPave((r)) and Eco-Optiloc((r))) and a Hydromedia((r)) Pervious Concrete
      pavement with runoff from an Asphalt control pavement. The usage of permeable
      pavements can mitigate the impact of urbanization on receiving surface water
      systems through quantity control and stormwater treatment. The PP systems
      provided excellent stormwater treatment for petroleum hydrocarbons, total
      suspended solids, metals (copper, iron, manganese and zinc) and nutrients (total
      nitrogen and total-phosphorus) by reducing event mean concentrations (EMC) as
      well as total pollutant loadings. The PPs significantly reduced the concentration
      and loading of ammonia (NH4(+)+NH3), nitrite (NO2(-)) and organic-nitrogen (Org
      N) but increased the concentration and loading of nitrate (NO3(-)). The PP
      systems had mixed performances for the treatment of phosphate (PO4(3-)). The PP
      systems increased the concentration of sodium (Na) and chloride (Cl) but EMCs
      remained well below recommended levels for drinking water quality. Relative to
      the observed runoff, winter road salt was released more slowly from the PP
      systems resulting in elevated spring and early-summer Cl and Na concentrations in
      effluent. PP materials were found to introduce dissolved solids into the
      infiltrating stormwater. The release of these pollutants was verified by
      additional laboratory scale testing of the individual pavement and aggregate
      materials at the University of Guelph. Pollutant concentrations were greatest
      during the first few months after construction and declined rapidly over the
      course of the study. 

PMID- 24681367
TI  - Sustainability of forest management under changing climatic conditions in the
      southern United States: adaptation strategies, economic rents and carbon
      sequestration.
AB  - The impacts of climate change on profitability and carbon storage in even-aged
      forest stands of two dominant commercial pine species, loblolly and slash pine,
      in the southern United States were assessed under alternative assumptions about
      the impact of climate change on forest productivity and catastrophic disturbance
      rates. Potential adaptation strategies to reduce losses from disturbance
      included: 1) alternative planting densities, and 2) planting slash pine instead
      of loblolly pine. In addition, the amount of sequestered carbon was used to
      develop an index of economic efficiency for carbon sequestration, which further
      helps rank the suitability of alternative adaptation strategies. Our results
      indicate that greater economic rents from forests occur with lower planting
      densities and the substitution of slash pine for high density loblolly pine.
      However, less carbon is sequestered by low density loblolly pine compared to
      slash pine and high density loblolly pine. Both adaptation strategies are
      economically more effective in terms of carbon sequestration compared to the
      baseline since they generate more economic revenues per Mg of sequestered carbon.

PMID- 24681368
TI  - [Why people delay seeking care after a positive HIV test: a qualitative study in
      Burkina].
AB  - Delayed care-seeking occurs when a person who received a positive HIV serology
      test result does not immediately seek medical treatment for this HIV infection.
      It has serious consequences for patient survival. This study aims to analyze the
      factors leading to delayed care-seeking in this circumstance. METHODOLOGY:
      Applying a qualitative approach, we conducted individual interviews and focus
      groups in 9 community-based organizations of people living with HIV and AIDS in
      Burkina Faso. In total, 112 people including 70 HIV-positive patients, 30
      healthcare providers, and 12 people leaving the laboratory after an HIV test,
      were interviewed. A thematic content analysis identified the factors that delayed
      care-seeking. RESULTS: Several factors explain the delay in seeking care. The
      weight of the negative representations of HIV and AIDS, its impact on those
      diagnosed with them, and fear of stigmatization (especially by family members)
      are major factors in delayed care. The poor quality of pre- and post-test
      counseling is another factor. This study also shows that financial barriers
      remain important in this delay. CONCLUSION: These findings suggest that earlier
      HIV care may be possible through efforts to reduce stigma, removal of financial
      barriers, and improvement of the quality of pre- and post-test counseling in
      mobile-device strategies and during large-scale testing campaigns.

PMID- 24681369
TI  - Bio-inspired impact-resistant composites.
AB  - Through evolutionary processes, biological composites have been optimized to
      fulfil specific functions. This optimization is exemplified in the mineralized
      dactyl club of the smashing predator stomatopod (specifically, Odontodactylus
      scyllarus). This crustacean's club has been designed to withstand the thousands
      of high-velocity blows that it delivers to its prey. The endocuticle of this
      multiregional structure is characterized by a helicoidal arrangement of
      mineralized fiber layers, an architecture which results in impact resistance and
      energy absorbance. Here, we apply the helicoidal design strategy observed in the
      stomatopod club to the fabrication of high-performance carbon fiber-epoxy
      composites. Through experimental and computational methods, a helicoidal
      architecture is shown to reduce through-thickness damage propagation in a
      composite panel during an impact event and result in an increase in toughness.
      These findings have implications in the design of composite parts for aerospace,
      automotive and armor applications. 

PMID- 24681370
TI  - Eggshell membrane biomaterial as a platform for applications in materials
      science.
AB  - Eggshell membrane (ESM) is a unique biomaterial, which is generally considered as
      waste. However, it has extraordinary properties which can be utilized in various
      fields and its potential applications are therefore now being widely studied. The
      first part of this review focuses on the chemical composition and morphology of
      ESM. The main areas of ESM application are discussed in the second part. These
      applications include its utilization as a biotemplate for the synthesis of
      nanoparticles; as a sorbent of heavy metals, organics, dyes, sulfonates and
      fluorides; as the main component of biosensors; in medicine; and various other
      applications. For each area of interest, a detailed literature survey is given. 

PMID- 24681371
TI  - Characterization of aqueous interactions of copper-doped phosphate-based glasses
      by vapour sorption.
AB  - Owing to their adjustable dissolution properties, phosphate-based glasses (PGs)
      are promising materials for the controlled release of bioinorganics, such as
      copper ions. This study describes a vapour sorption method that allowed for the
      investigation of the kinetics and mechanisms of aqueous interactions of PGs of
      the formulation 50P2O5-30CaO-(20-x)Na2O-xCuO (x=0, 1, 5 and 10mol.%). Initial
      characterization was performed using (31)P magic angle spinning nuclear magnetic
      resonance and attenuated total reflectance-Fourier transform infrared
      spectroscopy. Increasing CuO content resulted in chemical shifts of the
      predominant Q(2) NMR peak and of the (POP)as and (PO(-)) Fourier transform
      infrared absorptions, owing to the higher strength of the POCu bond compared to
      PONa. Vapour sorption and desorption were gravimetrically measured in PG powders
      exposed to variable relative humidity (RH). Sorption was negligible below 70% RH
      and increased exponentially with RH from 70 to 90%, where it exhibited a negative
      correlation with CuO content. Vapour sorption in 0% and 1% CuO glasses resulted
      in phosphate chain hydration and hydrolysis, as evidenced by protonated Q(0)(1H)
      and Q(1)(1H) species. Dissolution rates in deionized water showed a linear
      correlation (R(2)>0.99) with vapour sorption. Furthermore, cation release rates
      could be predicted based on dissolution rates and PG composition. The release of
      orthophosphate and short polyphosphate species corroborates the action of
      hydrolysis and was correlated with pH changes. In conclusion, the agreement
      between vapour sorption and routine characterization techniques in water
      demonstrates the potential of this method for the study of PG aqueous reactions. 

PMID- 24681372
TI  - Accelerated cell-sheet recovery from a surface successively grafted with
      polyacrylamide and poly(N-isopropylacrylamide).
AB  - A double polymeric nanolayer consisting of poly(N-isopropylacrylamide) (PIPAAm)
      and hydrophilic polyacrylamide (PAAm) was deposited on tissue culture polystyrene
      (TCPS) surfaces using electron beam irradiation to form a new temperature
      responsive cell culture surface in which the basal hydrophilic PAAm component in
      the double polymeric layer promotes the hydration of the upper PIPAAm layer and
      induces rapid cell detachment compared to a conventional temperature-responsive
      cell culture surface, PIPAAm-grafted TCPS (PIPAAm-TCPS). Take-off angle-dependent
      X-ray photoelectron spectroscopy spectral analysis demonstrated that the grafted
      PIPAAm and PAAm components were located in the upper and basal regions of the
      double polymeric layer, respectively, suggesting that the double polymeric layer
      forms an inter-penetrating-network-like structure with PAAm at the basal portion
      of the PIPAAm grafted chains. The wettability of the temperature-responsive cell
      culture surfaces with the double polymeric layer tended to be more hydrophilic,
      with an increase in the basal PAAm graft density at a constant PIPAAm graft
      density. However, when the graft densities of the upper PIPAAm and basal PAAm
      were optimized, the resulting temperature-responsive cell culture surface with
      the double polymeric layer exhibited rapid cell detachment while maintaining cell
      adhesive character comparable to that of PIPAAm-TCPS. The cell adhesive character
      was altered from cell-adhesive to cell-repellent with increasing PAAm or PIPAAm
      graft density. The cell adhesive character of the temperature-responsive cell
      culture surfaces was relatively consistent with their contact angles. These
      results strongly suggest that the basal PAAm surface properties affect the degree
      of hydration and dehydration of the subsequently grafted PIPAAm. In addition, the
      roles of the hydrophilic component in accelerating cell detachment are further
      discussed in terms of the mobility of the grafted PIPAAm chains. Applications of
      this insight might be useful for designing temperature-responsive cell culture
      surfaces for achieving efficient cell culture and quick target cell detachment. 

PMID- 24681373
TI  - Three-dimensional hydrogel scaffolds facilitate in vitro self-renewal of human
      skin-derived precursors.
AB  - Skin-derived precursors (SKPs) are multipotent cells with dermal stem cell
      properties. These easily available cells possess the capacity to reconstitute the
      skin in vivo, as well as a broader differentiation potential in vitro, which
      endows them with great prospects in regenerative medicine. However, the present
      authors' group and others previously found that adult human SKPs (hSKPs) expanded
      deficiently in vitro, which largely counteracted their research and practical
      values. Taking the physiological micro-environment of hSKPs into consideration,
      the authors sought to establish a hydrogel scaffold-based three-dimensional (3-D)
      culture system for hSKPs in the present study. After comparing their morphology,
      growth characteristics, signature gene expression and differentiation potential
      in different hydrogels, the present authors found that a chemically defined
      hyaluronic acid and denatured collagen-based hydrogel system that mimicked the
      natural niche of hSKPs in the dermis could alleviate hSKP senescence, support
      hSKP proliferation as spheres, while largely retaining their properties and
      potential. This study suggested that recapitulating the in vivo stem cell niche
      by providing them with 3-D extracellular matrix environments could help them
      achieve better self-renewal in vitro. In addition, the animal-origin-free and
      biocompatible 3-D hydrogel system will certainly benefit fundamental research and
      clinical applications of hSKPs in the near future. 

PMID- 24681374
TI  - A temperature-induced and shear-reversible assembly of latanoprost-loaded
      amphiphilic chitosan colloids: characterization and in vivo glaucoma treatment.
AB  - Hydrogels composed of assembled colloids is a material class that is currently
      receiving much interest and shows great promise for use in biomedical
      applications. This emerging material class presents unique properties derived
      from the combination of nanosized domains in the form of colloidal particles with
      a continuous gel network and an interspersed liquid phase. Here we developed an
      amphiphilic chitosan-based, thermogelling, shear-reversible colloidal gel system
      for improved glaucoma treatment and addressed how preparation procedures and
      loading with the anti-glaucoma drug latanoprost and commonly used preservative
      benzalkonium chloride influenced the mechanical properties of and drug release
      from the colloidal gels. The results highlight that incorporated substances and
      preparation procedures have effects both on mechanical properties and drug
      release, but that the release of drug loaded in the colloidal carriers is mainly
      limited by transport out of the carriers, rather than by diffusion within the
      gel. The developed colloidal chitosan based gels hold outstanding biomedical
      potential, as confirmed by the ease of preparation and administration, low
      cytotoxicity in MTT assay, excellent biocompatibility and lowering of intraocular
      pressure for 40 days in a rabbit glaucoma model. The findings clearly justify
      further investigations towards clinical use in the treatment of glaucoma.
      Furthermore, the use of this shear-reversible colloidal gel could easily be
      extended to localized treatment of a number of critical conditions, from chronic
      disorders to cancer, potentially resulting in a number of new therapeutics with
      improved clinical performance.

PMID- 24681376
TI  - The size of surface microstructures as an osteogenic factor in calcium phosphate
      ceramics.
AB  - The microporosity of calcium phosphate (CaP) ceramics has been shown to have an
      essential role in osteoinduction by CaP ceramics after ectopic implantation. Here
      we show that it is not the microporosity but the size of surface microstructural
      features that is the most likely osteogenic factor. Two tricalcium phosphate
      (TCP) ceramics, namely TCP-S and TCP-B, were fabricated with equivalent chemistry
      and similar microporosity but different sizes of surface microstructural
      features. TCP-S has a grain size of 0.99 +/- 0.20 MUm and a micropore size of
      0.65 +/- 0.25 MUm, while TCP-B displays a grain size of 3.08 +/- 0.52 MUm and a
      micropore size of 1.58 +/- 0.65 MUm. In vitro, both cell proliferation and
      osteogenic differentiation were significantly enhanced when human bone marrow
      stromal cells were cultured on TCP-S without any osteogenic growth factors,
      compared to TCP-B ceramic granules. The possible involvement of direct contact
      between cells and the TCP ceramic surface in osteogenic differentiation is also
      shown with a trans-well culture model. When the ceramic granules were implanted
      in paraspinal muscle of dogs for 12 weeks, abundant bone was formed in TCP-S (21
      +/- 10% bone in the available space), whereas no bone was formed in any of the
      TCP-B implants. The current in vitro and in vivo data reveal that the readily
      controllable cue, i.e. the size of the surface microstructure, could be
      sufficient to induce osteogenic differentiation of mesenchymal stem cells,
      ultimately leading to ectopic bone formation in calcium phosphate ceramics.

PMID- 24681375
TI  - Effect of amorphous phases during the hydraulic conversion of alpha-TCP into
      calcium-deficient hydroxyapatite.
AB  - Powders of alpha-tricalcium phosphate (alpha-TCP), which readily react with water
      to form calcium-deficient hydroxyapatite (CDHA), are frequently used in bone
      cements. As, for clinical applications, it is important to adjust the setting
      reaction of the cements to a reasonable reaction time, exact knowledge of the
      hydration mechanism is essential. It is known that prolonged milling results in
      partial amorphization of alpha-TCP powders and that dissolution of the amorphous
      phase significantly accelerates the hydration, but it is not clear yet when the
      amorphous phase reacts in comparison to the crystalline alpha-TCP. Therefore the
      aim of this study was to investigate the development of quantitative phase
      content of alpha-TCP samples during hydration. For this purpose, three alpha-TCP
      powders, containing 0, 16 and 71wt.% of amorphous phase (ATCP), were mixed with
      either deionized water or a 0.1M Na2HPO4 aqueous solution. The crystalline
      evolution of the paste was assessed quantitatively during the first 48h of
      hydration at 23 degrees C by G-factor quantification. The present investigations
      demonstrate that ATCP reacted earlier than crystalline alpha-TCP. The results
      also suggest the formation of an X-ray amorphous phase during the hydraulic
      conversion formation of alpha-TCP into CDHA. 

PMID- 24681377
TI  - Assessment of relative potential for Legionella species or surrogates inhalation
      exposure from common water uses.
AB  - The Legionella species have been identified as important waterborne pathogens in
      terms of disease morbidity and mortality. Microbial exposure assessment is a tool
      that can be utilized to assess the potential of Legionella species inhalation
      exposure from common water uses. The screening-level exposure assessment
      presented in this paper developed emission factors to model aerosolization,
      quantitatively assessed inhalation exposures of aerosolized Legionella species or
      Legionella species surrogates while evaluating two generalized levels of assumed
      water concentrations, and developed a relative ranking of six common in-home uses
      of water for potential Legionella species inhalation exposure. Considerable
      variability in the calculated exposure dose was identified between the six
      identified exposure pathways, with the doses differing by over five orders of
      magnitude in each of the evaluated exposure scenarios. The assessment of exposure
      pathways that have been epidemiologically associated with legionellosis
      transmission (ultrasonic and cool mist humidifiers) produced higher estimated
      inhalation exposure doses than pathways where epidemiological evidence of
      transmission has been less strong (faucet and shower) or absent (toilets and
      therapy pool). With consideration of the large uncertainties inherent in the
      exposure assessment process used, a relative ranking of exposure pathways from
      highest to lowest exposure doses was produced using culture-based measurement
      data and the assumption of constant water concentration across exposure pathways.
      In this ranking, the ultrasonic and cool mist humidifier exposure pathways were
      estimated to produce the highest exposure doses, followed by the shower and
      faucet exposure pathways, and then the toilet and therapy pool exposure pathways.

PMID- 24681378
TI  - Star-shaped polymers of bio-inspired algae core and poly(acrylamide) and
      poly(acrylic acid) as arms in dissolution of silica/silicate.
AB  - Silica, in natural waters (due to weathering of rocks) decreases system
      performance in water processing industry due to scaling. In view of that, the
      present work involves the synthesis of novel green star shaped additives of algae
      core (a bio-inspired material as diatom maintains silicic acid equilibrium in sea
      water) as silica polymerization inhibitors. Star shaped materials with bio
      inspired core and poly(acrylamide) [poly(AAm)] and poly(acrylic acid) [poly(AAc)]
      arms were synthesized by economical green approach. The proficiency was evaluated
      in 'mini lab' scale for the synthesized APAAm (Algae-g-poly(AAm)) and APAAc
      (Algae-g-poly(AAc)) dendrimers (star shaped) in colloidal silica
      mitigation/inhibition at 35  degrees C and 55  degrees C. Synthesized dendrimers
      were equally proficient in silica inhibition at 12 h and maintains >=450 ppm
      soluble silica. However, APAAm dendrimers of generation 0 confirmed better
      results (~300 ppm) in contrast to APAAc dendrimers in silica inhibition at 55 
      degrees C. Additionally, dendrimers also worked as a nucleator for heterogeneous
      polymerization to inhibit silica homo-polymerization. APAAm dendrimer test set
      showed no silica deposit for more than 10 days of inhibition. EDX
      characterization results support nucleator mechanism with Si content of 6.97%
      10.98% by weight in silica deposits (SiO2-APAAm dendrimer composites). 

PMID- 24681379
TI  - Nitrification in lake sediment with addition of drinking water treatment
      residuals.
AB  - Drinking water treatment residuals (WTRs), non-hazardous by-products generated
      during potable water production, can effectively reduce the lake internal
      phosphorus (P) loading and improve water quality in lakes. It stands to reason
      that special attention regarding the beneficial reuse of WTRs should be given not
      only to the effectiveness of P pollution control, but also to the effects on the
      migration and transformation of other nutrients (e.g., nitrogen (N)). In this
      work, based on laboratory enrichment tests, the effects of WTRs addition on
      nitrification in lake sediment were investigated using batch tests, fluorescence
      in situ hybridization, quantitative polymerase chain reaction and phylogenetic
      analysis techniques. The results indicated that WTRs addition had minor effects
      on the morphologies of AOB and NOB; however, the addition slightly enhanced the
      sediment nitrification potential from 12.8 to 13.2 MUg-N g(-1)-dry sample h(-1)
      and also increased the ammonia oxidation bacteria (AOB) and nitrite oxidizing
      bacteria (NOB) abundances, particularly the AOB abundances (P < 0.05), which
      increased from 1.11 * 10(8) to 1.31 * 10(8) copies g(-1)-dry sample. Moreover,
      WTRs addition was beneficial to the enrichment of Nitrosomonas and Nitrosospira
      multiformis and promoted the emergence of a new Nitrospira cluster, causing the
      increase in AOB and NOB diversities. Further analysis showed that the variations
      of nitrification in lake sediment after WTRs addition were primarily due to the
      decrease of bioavailable P, the introduction of new nitrifiers and the increase
      of favorable carriers for microorganism attachment in sediments. Overall, these
      results suggested that WTRs reuse for the control of lake internal P loading
      would also lead to conditions that are beneficial to nitrification. 

PMID- 24681380
TI  - Seizure outcome after AED failure in pediatric focal epilepsy: impact of
      underlying etiology.
AB  - OBJECTIVE: This study aimed to identify long-term seizure outcome in pediatric
      nonsyndromic focal epilepsy after failure of serial antiepileptic drugs (AEDs)
      due to lack of efficacy. METHODS: Children (1 month-17 years) with new-onset
      focal epilepsy not meeting the criteria for a defined electroclinical syndrome
      diagnosed between 1980 and 2009 while residing in Olmsted County, MN, were
      retrospectively identified. Medical records of those followed for >=2 years were
      reviewed to assess etiology, the number of AEDs that failed due to lack of
      efficacy, and seizure outcome at final follow-up. Etiology was classified into
      structural/metabolic, genetic, or unknown. Favorable outcome was defined as
      seizure freedom >=1 year, on or off AEDs, without prior epilepsy surgery. Poor
      outcome was defined as ongoing seizures in the preceding year or having undergone
      prior epilepsy surgery. RESULTS: Nonsyndromic focal epilepsy accounted for
      275/468 (59%) of all patients with newly diagnosed epilepsy--of these, 256 (93%)
      were followed for a minimum of two years and were included in the study. Median
      duration of follow-up was 10.0 years. At least one AED had failed due to lack of
      efficacy in 100 (39.1%) children. Favorable outcomes occurred in 149/156 (95.5%)
      children with no AED failure, 16/30 (53.3%) with one AED failure, 8/25 (32%) with
      two AED failures, and only 2/45 (4.4%) with three AED failures. After two AED
      failures, the seizures of nearly one-quarter of children who had epilepsy with an
      unknown cause responded favorably to the third AED compared with only 7.8% of the
      cohort that had epilepsy with a structural/metabolic cause. Children with a
      remote brain insult had a significantly higher likelihood of favorable outcome
      with serial AEDs than those with other structural abnormalities. SIGNIFICANCE:
      Etiology is an important determinant of pharmacoresistance in nonsyndromic focal
      epilepsy. Surgical evaluation should be considered after failure of 1-2 AEDs in
      those who have epilepsy with structural causes, excluding remote brain insults.
      Conversely, as surgical success is lower with normal MRI or more diffuse brain
      insults, it appears reasonable to hold off surgical evaluation until 2-3 AEDs
      have failed in such children.

PMID- 24681381
TI  - Responsive neurostimulation in epilepsy therapy: some answers, lingering
      questions.

PMID- 24681382
TI  - The social context of anxiety and depression: exploring the role of anxiety and
      depression in the lives of Australian adults with epilepsy.
AB  - AIM: To examine key determinants of anxiety and depression in a community sample
      of people with epilepsy. METHOD: Data were analyzed from the 2010 Australian
      Epilepsy Longitudinal Survey, examining living with epilepsy in Australia. The
      HADS was analyzed, and Pearson correlations and block recursive regression were
      undertaken to identify key associations between anxiety, depression, and a range
      of variables and to identify key determinants of anxiety and depression. RESULTS:
      Key factors to influence anxiety were social aspects of stigma, effectiveness of
      seizure control, whether in employment, and the number of different epilepsy
      drugs. Determinants for depression were social aspects of stigma, whether in
      employment, and the effectiveness of seizure control. Stigma was also found to be
      an important mediating variable for employment, control, and the number of drugs.
      CONCLUSION: Understanding the mechanisms involved in anxiety and depression in a
      community sample of people with epilepsy requires the inclusion of opportunities
      for paid employment and the effects of psychosocial factors such as stigma.
      Without this fuller social context, there are limitations on understanding
      factors that influence anxiety and depression and how to deal with the outcomes.

PMID- 24681383
TI  - Caregiving in pediatric epilepsy: results of focus groups and implications for
      research and practice.
AB  - The process of caring for youth with epilepsy (YWEs) has been understudied.
      Previous research has identified that caregivers of YWEs report increased
      parenting stress, unanticipated caregiving responsibilities, and negative effects
      on family life. Using the adapted Caregiving Process Model, perceptions of the
      caregiving process were explored in four focus groups of caregivers of youth with
      epilepsy diagnosed at <1 year, between 1 and 5 years, and >5 years. Thematic
      analysis guided the data analysis. The prevalent theme that emerged during the
      data analysis was navigating the noncontingencies (lack of a perceived
      relationship between action and outcome, unpredictability). This was supported by
      the subthemes, namely, blessings and sacrifices, uncertainty today and tomorrow,
      constant vigilance, and caregiving is more than parenting. The focus groups
      displayed similarities and differences in caregiving perceptions across the three
      postdiagnosis time periods, providing support for conceptualization of the
      caregiving as multifactorial, multidirectional, and fluid process. With this
      knowledge, epilepsy health-care professionals are encouraged to promote patient
      and family centeredness, provide information on how to access community
      resources, and work with caregivers to enhance epilepsy self-management skills.

PMID- 24681384
TI  - Knowledge and attitudes towards epilepsy in Zambia: a questionnaire survey.
AB  - Misconception and stigma towards epilepsy have a profound impact on this disease
      in Africa. An unselected sample of Zambian people was interviewed to investigate
      their knowledge and attitudes towards epilepsy. Proper/improper answers were
      scored, and a composite score was developed with negative values for
      unsatisfactory awareness and high stigma levels. The sample comprised 231 people
      residing in urban (107) or in rural (124) areas. The median and interquartile
      range of scores for epilepsy awareness and stigma were, respectively, -1 (-3; +1)
      and +1 (-1; +6). Poor education was the only significant predictor of
      unsatisfactory awareness (p=0.0131), while education and residency were
      significantly associated with stigma (p<0.0001 and p=0.0004). Rural people were
      mostly in the highest stigma level (44.2%) and urban people in the lowest stigma
      level (60.4%). Misconception and negative attitudes towards epilepsy among
      Zambian people reflect poor education and rural residency. 

PMID- 24681385
TI  - Overlap between dissociation and other psychological characteristics in patients
      with psychogenic nonepileptic seizures.
AB  - Patients with psychogenic nonepileptic seizures (PNES) often report symptoms of
      dissociation. However, it is unclear how these symptoms relate to
      psychotherapeutic treatment, for example, with cognitive-behavioral therapy
      (CBT). Here, we investigated the degree of overlap between symptoms of
      dissociation and other psychiatric features that are more traditional targets for
      CBT. We used a hierarchical linear regression to measure the variance associated
      with dissociative symptoms (as assessed by the Dissociative Experiences Scale -
      DES) among 46 individuals with PNESs. The regression predictor variables are
      indices of participants' self-rated mood, self-efficacy, quality of life, locus
      of control, and life outlook (e.g., optimism). Results revealed that 70.2% of the
      variance associated with DES score was explained by psychological distress and
      locus of control. The other factors examined did not make a significant
      contribution to the regression model. These results suggest that traditional CBT
      targets - mood symptoms, mood distress, and dysfunctional beliefs about locus of
      control - overlap substantially with self-reported dissociative symptoms. 

PMID- 24681386
TI  - Screening for depression in people with epilepsy: comparative study among
      neurological disorders depression inventory for epilepsy (NDDI-E), hospital
      anxiety and depression scale depression subscale (HADS-D), and Beck depression
      inventory (BDI).
AB  - PURPOSE: We aimed to assess and compare the psychometric properties of the
      Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Hospital
      Anxiety and Depression Scale Depression Subscale (HADS-D), and Beck Depression
      Inventory (BDI) as screening instruments for depression and suicidality in people
      with epilepsy. METHODS: One hundred twenty-six people (54% women) diagnosed with
      epilepsy were recruited and evaluated on their sociodemographic and clinical
      features. Depression and suicide risk were assessed with a structured psychiatric
      interview, the Mini International Neuropsychiatric Interview (MINI-Plus), and the
      performance of NDDI-E, HADS-D, and BDI was evaluated. RESULTS: The sensitivity
      and specificity of BDI for the diagnosis of depression was around 90%; HADS-D and
      NDDI-E have sensitivity higher than 80%, and specificity was greater than 75%.
      For identifying suicide risk, the NDDI-E sensitivity was 92.9%, and HADS-D
      sensitivity was 85.7%, and a reasonable specificity (68%) was observed for both
      instruments. All instruments showed a negative predictive value of over 90%.
      Comparisons of the areas under the ROC curve for these instruments were not
      significantly different regarding depression or moderate/severe risk of suicide.
      CONCLUSION: All three instruments evaluated have clinical utility in the
      screening of depression in people with epilepsy. Both NDDI-E and HADS-D are brief
      efficient screening instruments to identify depression in people with epilepsy.
      The BDI is a more robust instrument, but it takes longer to apply, which hampers
      its use by busy clinicians and by people with cognitive impairment.

PMID- 24681387
TI  - Cognitive motor interference during walking in multiple sclerosis using an
      alternate-letter alphabet task.
AB  - OBJECTIVE: To examine cognitive motor interference (CMI) during walking using a
      simple, standardized, and well-refined alphabet dual-task (DT) paradigm in
      individuals with multiple sclerosis (MS) in whom cognitive and walking impairment
      often co-occur. DESIGN: A single time point, cross-sectional study. SETTING: A
      university clinical laboratory. PARTICIPANTS: Individuals with MS (N=61; mean age
      +/- SD, 50.8+/-9.3 y) performed 4 walking trials over a 4.6-m walkway to
      determine gait parameters. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Gait parameters were assessed over 4 walking trials. The first 2 walks involved
      the single task (ST) of walking only; the second 2 walks involved participants
      performing the DT of reciting alternate letters of the alphabet while walking.
      The gait parameters recorded during the ST and DT walks were used to compute a
      dual-task cost (DTC) of walking (% change in gait parameter between ST and DT
      walks) as a metric of CMI. RESULTS: Our multivariate analysis with univariate
      follow-ups indicated CMI during walking based on slower velocity (etap(2)=.59;
      F=84.6; P<.001) and cadence (etap(2)=.46; F=51.6; P<.001), shorter step length
      (etap(2)=.38; F=36; P<.001), and increased step time (etap(2)=.34; F=31; P<.001)
      and double-support time (etap(2)=.31; F=27.3; P<.001) in DT versus ST conditions.
      The DTC of walking for the gait parameters was not correlated with clinical
      (disability, disease duration) and demographic (eg, education, age) factors (all
      |r|<=.240). CONCLUSIONS: The alphabet DT paradigm is easily administered and well
      refined. We highlight its ability and acceptability to determine CMI during
      walking in people with MS, independent of disease status.

PMID- 24681388
TI  - Reference values and psychometric properties of the lower extremity motor
      coordination test.
AB  - OBJECTIVES: (1) To create predictive nomograms for the dominant and nondominant
      limbs on the Lower Extremity Motor Coordination Test (LEMOCOT) using reference
      values, and (2) to determine the inter- and intrarater reliability for the
      LEMOCOT; the best scoring method (first vs mean of the first 2 vs mean of the
      last 2 vs mean of 3 vs the highest of 3 trials); the best testing method (direct
      vs video observation); and the ability to detect real change (smallest real
      difference [SRD] and standard error of the measurement [SEM]). DESIGN: Normative
      and methodological study. SETTING: Metropolitan area. PARTICIPANTS: Healthy
      individuals (N=320, 50% women) in 7 age groups: 20 to 29, 30 to 39, 40 to 49, 50
      to 59, 60 to 69, 70 to 79, and >=80 years. Each group had 50 participants, except
      for >=80 years (n=20). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE
      LEMOCOT RESULTS: Age and sex explained 48% of the variance in the LEMOCOT scores
      for the dominant limb and 44% for the nondominant limb (125<F<148; P<.001). No
      significant differences were found regarding the different scoring methods
      (.12<F<1.02; .10<P<.92), and all of them demonstrated good reliability
      (intraclass correlation coefficients between .90 and .99; P<.001). There was
      agreement between scores from direct and video observation (limits of agreement 
      1.99 to 1.85; -1.55 to 1.62). Appropriate SEM (2.27-1.85) and SRD (6.27-5.11)
      values were found. CONCLUSIONS: Reference values were determined for the LEMOCOT,
      and predictive nomograms were created based on age and sex. The LEMOCOT is
      reliable, needing only 1 trial (after familiarization) to generate reliable
      scores; can be scored from either direct or video observation; and has the
      ability to detect real change over time.

PMID- 24681389
TI  - Low molecular weight PEI-appended polyesters as non-viral gene delivery vectors.
AB  - Routine clinical implementation of human gene therapy requires safe and efficient
      gene delivery methods. Linear biodegradable polyesters with carbon-carbon double
      bonds are prepared from unsaturated diacids and diols. Subsequent appending of
      low molecular weight PEI by Michael addition gives target cationic polymers
      efficiently. Agarose gel retardation and fluorescence quenching assays show that
      these materials have good DNA binding ability and can completely retard plasmid
      DNA at weight ratio of 0.8. The formed polyplexes have appropriate sizes around
      275 nm and zeta-potential values about +20-35 mV. The cytotoxicities of these
      polymers assayed by MTT are much lower than that of 25 kDa PEI. In vitro
      transfection toward 7402, HEK293 and U-2OS cells show that polymer P1 may give
      dramatically higher transfection efficiency (TE) than 25 kDa PEI, especially in U
      2OS cells, suggesting that such polymer might be promising non-viral gene
      vectors. 

PMID- 24681390
TI  - 6-Amino-2,4,5-trimethylpyridin-3-ols: a new general synthetic route and
      antiangiogenic activity.
AB  - A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5
      trimethylpyridin-3-ols from pyridoxine.HCl via a six-step sequence has been
      developed. This approach features an introduction of various amino groups to C(6)
      position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate,
      by a Buchwald-Hartwig amination reaction using palladium(0) transition metal,
      which certainly renders an expanded scope of amino substituents. Some analogs
      prepared using the methods described here showed high level of antiangiogenic and
      antitumor activities in chick chorioallantoic membrane (CAM) assay, demonstrating
      the potential of these new aminopyridinols as antiangiogenic agents. 

PMID- 24681391
TI  - New aminobenzenesulfonamide-thiourea conjugates: synthesis and carbonic anhydrase
      inhibition and docking studies.
AB  - A variety of 1-substituted-3-(3-aminosulfonylphenyl)thioureas (3a-k) and two new
      1-aroyl-3-(4-aminosulfonylphenyl)thiourea derivatives (5a and 5b) were
      synthesized by reaction of 3-aminobenzenesulfonamide and 4
      aminobenzenesulfonamide respectively with freshly prepared aroyl/heteroaryl
      isothiocyanates in dry acetonitrile. FTIR, (1)H NMR, (13)C NMR, GC-MS and
      elemental analyses data confirmed the assigned structures to the synthesized
      compounds. Further structure of compound (3g) was also confirmed by single
      crystal XRD analysis. The compounds were investigated as inhibitors of the bovine
      erythrocyte carbonic anhydrase isoform II (bCA II). The inhibition constants of
      these compounds against bCA II were in the range 0.011-17.1 MUM. Among the
      evaluated compounds, 1-substituted -3-(3-aminosulfonylphenyl)thiourea derivatives
      3h and 5a were the most potent inhibitors with IC50 of 0.052 and 0.011 MUM,
      respectively. In silico docking and molecular dynamics simulation studies were
      performed against bCA II and human CA II enzymes to rationalize the inhibitory
      properties of these compounds. 

PMID- 24681392
TI  - Investigating electrochemical removal of bacterial biofilms from stainless steel
      substrates.
AB  - Electrochemical removal of biofilms deserves attention because of its ease of use
      and environmentally friendly nature. We investigated the influence of electrode
      potential and treatment time on the removal of a 10-day old Pseudomonas
      aeruginosa biofilm formed on stainless steel 316 L substrates. At electrode
      potentials more positive than -1.5 V vs. Ag/AgCl, lower removal rates were
      observed and only partial removal of the biofilm was achieved during a 1-min time
      interval. Electrostatic repulsion between the film and electrode surface is
      believed to drive biofilm detachment under these conditions. However, when the
      biofilm-coated substrates were treated at potentials negative of -1.5 V vs.
      Ag/AgCl, complete removal of a biofilm was achieved within seconds. Under these
      conditions, vigorous evolution of hydrogen gas is believed to be responsible for
      the film removal, mechanically detaching the bacteria and extracellular polymeric
      matrix from the substrate. Stainless steel substrates were also subjected to
      repeated cycles of biofilm formation and electrochemical removal. High removal
      efficiencies were maintained throughout this process suggesting the potential of
      the proposed technology for application on conductive surfaces in various
      industrial settings.

PMID- 24681393
TI  - Dendrimer enriched single-use aptasensor for impedimetric detection of activated
      protein C.
AB  - A novel impedimetric aptasensor for detection of human activated protein C (APC)
      was introduced for the first time in the present study. An enhanced sensor
      response was obtained using poly(amidoamine) (PAMAM) dendrimer having 16
      succinamic acid surface groups (generation 2, G2-PS), that was modified onto the
      surface of screen printed graphite electrode (G2-PS/SPE). An amino modified DNA
      aptamer was then immobilized onto the surface of G2-PS modified SPE. The
      selective interaction of APT with its cognate protein, APC was investigated using
      different electrochemical techniques; differential pulse voltammetry (DPV),
      cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The
      microscopic characterization was consecutively performed before/after each
      modification/interaction step using scanning electron microscopy (SEM) and atomic
      force microscopy (AFM). The selectivity of aptasensor was tested in the presence
      of numerous proteins; protein C, thrombin, bovine serum albumin, factor Va and
      chromogenic substrate in different buffer mediums. The APC detection in the
      artificial serum; fetal bovine serum (FBS) was also performed impedimetrically.
      This dendrimer modified aptasensor technology brings several advantages: being
      single-use, fast screening with low-cost per measurement and resulting in
      sensitive detection of APC with the detection limits of 0.74 MUg/mL (0.46 pmol in
      35 MUL sample) in buffer medium, and 2.03 MUg/mL (1.27 pmol in 35 MUL sample) in
      serum.

PMID- 24681394
TI  - Effect of ionic liquids on the different hierarchical order of type I collagen.
AB  - The effect of ionic liquids (ILs) on proteins has been gaining huge interest due
      to easy tunability of cation and anion for generating the desired effect. This
      study explores the effect of alkyl imidazolium chloride ILs on collagen at
      molecular, inter-fibrillar and skin matrix level. Circular dichroic studies
      reveal that at the molecular level, the secondary structure of collagen was not
      affected by imidazolium ILs and there was no change in thermal stability as well.
      However, collagen at the inter-fibrillar level behaved differently. With increase
      in concentration of ILs, remarkable decrease in thermal stability of rat tail
      tendon (RTT) collagen fibers with marginal swelling effect was seen. SEM
      micrographs of skin matrix treated with IL show opening up of pores. This kind of
      exquisite behavior of ILs at different hierarchal order of collagen indicates
      that ILs are endowed with potential lyotropic action, which can be judiciously
      employed for biomedical applications. 

PMID- 24681395
TI  - Bacteria survival probability in bactericidal filter paper.
AB  - Bactericidal filter papers offer the simplicity of gravity filtration to
      simultaneously eradicate microbial contaminants and particulates. We previously
      detailed the development of biocidal block copolymer micelles that could be
      immobilized on a filter paper to actively eradicate bacteria. Despite the many
      advantages offered by this system, its widespread use is hindered by its unknown
      mechanism of action which can result in non-reproducible outcomes. In this work,
      we sought to investigate the mechanism by which a certain percentage of
      Escherichia coli cells survived when passing through the bactericidal filter
      paper. Through the process of elimination, the possibility that the bacterial
      survival probability was controlled by the initial bacterial load or the
      existence of resistant sub-populations of E. coli was dismissed. It was observed
      that increasing the thickness or the number of layers of the filter significantly
      decreased bacterial survival probability for the biocidal filter paper but did
      not affect the efficiency of the blank filter paper (no biocide). The survival
      probability of bacteria passing through the antibacterial filter paper appeared
      to depend strongly on the number of collision between each bacterium and the
      biocide-loaded micelles. It was thus hypothesized that during each collision a
      certain number of biocide molecules were directly transferred from the
      hydrophobic core of the micelle to the bacterial lipid bilayer membrane.
      Therefore, each bacterium must encounter a certain number of collisions to take
      up enough biocide to kill the cell and cells that do not undergo the threshold
      number of collisions are expected to survive. 

PMID- 24681396
TI  - Protein HESylation for half-life extension: synthesis, characterization and
      pharmacokinetics of HESylated anakinra.
AB  - Half-life extension (HLE) is becoming an essential component of the industrial
      development of small-sized therapeutic peptides and proteins. HESylation((r)) is
      a HLE technology based on coupling drug molecules to the biodegradable
      hydroxyethyl starch (HES). In this study, we report on the synthesis,
      characterization and pharmacokinetics of HESylated anakinra, where anakinra was
      conjugated to propionaldehyde-HES using reductive amination, leading to a
      monoHESylated protein. Characterization using size exclusion chromatography and
      dynamic light scattering confirmed conjugation and the increase in molecular
      size, while Fourier transform infrared spectroscopy showed that the secondary
      structure of the conjugate was not affected by coupling. Meanwhile,
      microcalorimetry and aggregation studies showed a significant increase in protein
      stability. Surface plasmon resonance and microscale thermophoresis showed that
      the conjugate retained its nanomolar affinity, and finally, the pharmacokinetics
      of the HESylated protein exhibited a 6.5-fold increase in the half-life, and a 45
      fold increase in the AUC. These results indicate that HESylation((r)) is a
      promising HLE technology. 

PMID- 24681397
TI  - Economic cycles and heart disease in Mexico.
AB  - While a considerable literature has emerged regarding the relationship between
      the business cycles and mortality rates, relatively little is known regarding how
      economic fluctuations are related to morbidity. We investigate the relationship
      between business cycles and heart disease in Mexico using a unique state-level
      dataset of 512 observations consisting of real GDP and heart disease incidence
      rates (overall and by age group) from 1995 to 2010. Our study is one of the first
      to use a state-level panel approach to analyze the relationship between the
      business cycle and morbidity. Further, the state and year fixed effects employed
      in our econometric specification reduce possible omitted variable bias. We find a
      general procyclical, although largely statistically insignificant,
      contemporaneous relationship. However, an increase in GDP per capita sustained
      over five years is associated with considerable increases in the incidence rates
      of ischemic heart disease and hypertension. This procyclical relationship appears
      strongest in the states with the lowest levels of development and for the oldest
      age groups. Our results suggest that economic fluctuations may have important
      lagged effects on heart disease in developing countries.

PMID- 24681398
TI  - Measurement of the Glenoid Track In Vivo as Investigated by 3-Dimensional Motion
      Analysis Using Open MRI.
AB  - BACKGROUND: A Hill-Sachs lesion is a common injury associated with anterior
      glenohumeral instability, and a Hill-Sachs lesion that engages with the anterior
      glenoid rim is 1 factor related to recurrent instability. In a cadaveric study in
      2007, a new concept, the "glenoid track," was proposed to evaluate the risk of
      engagement of Hill-Sachs lesions with the glenoid. PURPOSE: To investigate the
      glenoid track in vivo using a custom-developed noninvasive motion analysis
      system. STUDY DESIGN: Descriptive laboratory study. METHODS: Using a wide-gantry
      magnetic resonance imaging (MRI) scanner, the right shoulders of 30 healthy
      volunteers were examined. The MRI scans were taken of the right arm in 7 static
      supine positions from 0 degrees  to maximum abduction, keeping maximum external
      rotation and horizontal extension. Using the custom motion analysis system, 3
      dimensional models of the scapula and humerus were created from the MRI data.
      Then, the movement of the humerus and scapula was calculated using voxel-based
      registration of each model, and the motion of the glenoid on the humeral head was
      analyzed. RESULTS: The models demonstrated that glenoid contact shifted from the
      inferomedial to the superolateral portion of the humeral head. The mean widths of
      the glenoid track with the arm at 60 degrees , 90 degrees , 120 degrees , and 150
      degrees  of abduction were 20.7 +/- 4.5 mm, 19.4 +/- 3.9 mm, 18.9 +/- 2.7 mm, and
      18.7 +/- 2.5 mm (89%, 83%, 82%, and 81% of the glenoid width), respectively. The
      width of the glenoid track at 60 degrees  of abduction was significantly greater
      than those at 90 degrees , 120 degrees , and 150 degrees  of abduction (P =
      .0472, .0148, and .0083, respectively). There were no significant differences
      among widths measured at 90 degrees , 120 degrees , and 150 degrees  of
      abduction. CONCLUSION: The existence and widths of the glenoid track were
      confirmed in vivo.

PMID- 24681400
TI  - Calcium intake and serum calcium status in Mongolian children.
AB  - Dietary calcium intake in relation to calcium status in Mongolian children was
      investigated. This survey was a cross-sectional survey. A total of 835 children
      were randomly selected from 4 economic regions and Ulaanbaatar city. Information
      on dietary intake was collected from 835 children in the 1-3, 4-7, and 8-14 year
      old groups by a 24-h recall method. The average daily intake of calcium from diet
      was calculated for individuals. Blood samples were collected from 104 children.
      The mean of daily calcium intakes as 273+/-30.0mg in 1-3-year old children,
      309.0+/-30.0mg in 4-7 year old children, and 317.0+/-31.0mg in 8-14 year old
      children, respectively. There were statistically significant differences in
      calcium intakes between the age groups 1-3 years, 4-7 years, and 1-3 years, 8-14
      years of children (p<0.001). Calcium intakes in all studied children of all age
      groups were lower (39%, 30.9%, and 24.4%) than the recommended level of calcium
      intakes. In 22.1% of studied children, the serum total calcium concentration
      levels were below the normal range. Based on the total serum calcium, the
      prevalence of hypocalcemia was higher among children in the age group 8-14 years
      (27.6%) than the prevalence among children in the age group <1 year (p<0.05).
      Based on the corrected serum calcium values, the prevalence of hypocalcemia was
      higher (52.4%, 63.6%, and 51.1%) among children in the age groups 1-3, 4-7, and 8
      14 years. The mean level of corrected serum calcium were low (2.02+/-0.04, 2.05+/
      0.73, and 1.99+/-0.64mg) in children in the age groups 1-3, 4-7, and 8-14 years.
      These findings suggest that low dietary calcium intakes may be reflected by
      hypocalcemia in Mongolian children. In conclusion, there is a need to improve a
      consumption of milk, dairy products in Mongolian children. In addition, there is
      need to use a vitamin D supplementation with a calcium supplementation in
      children with severe vitamin D deficiency rickets. This article is part of a
      Special issue entitled "16th Vitamin D Workshop". 

PMID- 24681399
TI  - Gonadal development and transcript profiling of steroidogenic enzymes in response
      to 17alpha-methyltestosterone in the rare minnow Gobiocypris rarus.
AB  - It is well known that natural and anthropogenic chemicals interfere with the
      hormonal system of vertebrate and invertebrate organisms. How these chemicals
      regulate gonadal steroidogenesis remains to be determined. The main objective of
      this study was to evaluate the effects of 17alpha-methyltestosterone (MT), a
      synthetic model androgen, on gene expression profiles of six key steroidogenic
      genes in adult rare minnow. The full-length cDNA encoding 11beta-hydroxysteroid
      dehydrogenase-2 (11beta-HSD2) was firstly isolated and characterized by RT-PCR
      and RACE methods. The gonadal transcript changes of StAR, cyp11a1, 3beta-HSD,
      cyp17a1, 11beta-HSD2 and cyp19a1a in 6-month adult Gobiocypris rarus exposed to
      MT and 17alpha-ethinylestradiol (EE2) for 7, 14 and 21 days were detected by qRT
      PCR. To make an effort to connect the transcriptional changes of steroidogenic
      enzymes with effects on higher levels of biological organization and on VTG, one
      remarkable sensitive target of steroids, body and gonad weights, histology of
      gonads, and hepatic vtg mRNA level were measured. MT caused varying degree of
      abnormalities in ovaries and testes. The hepatic vtg mRNA level was highly
      inhibited in females and slightly altered in males by MT. Transcripts of several
      steroidogenic genes including StAR, cyp17a1, and cyp11a1 showed high
      responsiveness to MT exposure in G. rarus. The gene expression profiles of these
      steroidogenic genes in MT-treated groups were much distinct with the EE2-treated
      group. 

PMID- 24681402
TI  - Embodiment and second-language: automatic activation of motor responses during
      processing spatially associated L2 words and emotion L2 words in a vertical
      Stroop paradigm.
AB  - Converging evidence suggests that understanding our first-language (L1) results
      in reactivation of experiential sensorimotor traces in the brain. Surprisingly,
      little is known regarding the involvement of these processes during second
      language (L2) processing. Participants saw L1 or L2 words referring to entities
      with a typical location (e.g., star, mole) (Experiment 1 & 2) or to an emotion
      (e.g., happy, sad) (Experiment 3). Participants responded to the words' ink color
      with an upward or downward arm movement. Despite word meaning being fully task
      irrelevant, L2 automatically activated motor responses similar to L1 even when L2
      was acquired rather late in life (age >11). Specifically, words such as star
      facilitated upward, and words such as root facilitated downward responses.
      Additionally, words referring to positive emotions facilitated upward, and words
      referring to negative emotions facilitated downward responses. In summary our
      study suggests that reactivation of experiential traces is not limited to L1
      processing. 

PMID- 24681401
TI  - The neural changes in connectivity of the voice network during voice pitch
      perturbation.
AB  - Voice control is critical to communication. To date, studies have used
      behavioral, electrophysiological and functional data to investigate the neural
      correlates of voice control using perturbation tasks, but have yet to examine the
      interactions of these neural regions. The goal of this study was to use
      structural equation modeling of functional neuroimaging data to examine network
      properties of voice with and without perturbation. Results showed that the
      presence of a pitch shift, which was processed as an error in vocalization,
      altered connections between right STG and left STG. Other regions that revealed
      differences in connectivity during error detection and correction included
      bilateral inferior frontal gyrus, and the primary and pre motor cortices. Results
      indicated that STG plays a critical role in voice control, specifically, during
      error detection and correction. Additionally, pitch perturbation elicits changes
      in the voice network that suggest the right hemisphere is critical to pitch
      modulation. 

PMID- 24681403
TI  - Protein aggregation due to nsSNP resulting in P56S VABP protein is associated
      with amyotrophic lateral sclerosis.
AB  - Mutations in the gene encoding vesicle-associated membrane protein (VAPB) cause
      amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. The VAPB
      gene is mapped to chromosome number 20 and can be found at cytogenetic location
      20q13.33 of the chromosome. VAPB is seen to play a significant role in the
      unfolded protein response (UPR), which is a process that suppresses the
      accumulation of unfolded proteins in the endoplasmic reticulum. Earlier studies
      have reported two points; which we have analyzed in our study. Firstly, the
      mutation P56S in the VAPB is seen to increase the stability of the protein and
      secondly, the mutation P56S in VAPB is seen to interrupt the functioning of the
      gene and loses its ability to be involved in the activation of the IRE1/XBP1
      pathway which leads to ALS. With correlation on the previous research studies on
      the stability of this protein, we carried out Molecular dynamics (MD) simulation.
      We analyzed the SNP results of 17 nsSNPs obtained from dbSNP using SIFT,
      polyphen, I-Mutant, SNP&GO, PhDSNP and Mutpred to predict the role of nsSNPs in
      VAPB. MD simulation is carried out and plots for RMSD, RMSF, Rg, SASA, H-bond and
      PCA are obtained to check and prove the stability of the wild type and the mutant
      protein structure. The protein is checked for its aggregation and the results
      obtained show changes in the protein structure that might result in the loss of
      function. 

PMID- 24681404
TI  - Ant mound as an optimal shape in constructal design: solar irradiation and
      circadian brood/fungi-warming sorties.
AB  - Sizes, shapes, ambient and in-dome temperature, incoming solar radiation and
      illumination are measured on a Formica rufa anthill in a mixed forest of the
      Volga-Kama National Reserve in Russia. These data are used in a conceptual model
      of insolation of a right conical surface by direct-beam, descending atmospheric
      and ascending ground-reflected radiation. Unlike a standard calculation of the
      energy flux intercepted by a solar panel, the anthill is a 3-D structure and
      double-integration of the cosine of the angle between the solar beams and normal
      to the surface is carried out for a "cozy trapezium", where the insects expose
      themselves and the brood to "morning" sunbathing pulses (Jones and Oldroyd,
      2007). Several constructal design problems are formulated with the criteria
      involving either a pure solar energy gained by the dome or this energy, as a
      mathematical criterion, penalized by additive terms of mechanical energy
      (potential and friction) lost by the ants in their diurnal forays from a
      "heartland" of the nest to the sun-basking zone on the surface. The unique and
      global optima are analytically found, with the optimal tilt angle of the cone
      explicitly expressed through the zenith angle of the Sun and meteorological
      constants for the isotropic sky model. 

PMID- 24681405
TI  - "A little information excites us." Consumer sensory experience of Vermont artisan
      cheese as active practice.
AB  - This research is concerned with explaining consumer preference for Vermont
      artisan cheese and the relationship between that preference and sensory
      experience. Artisan cheesemaking is increasingly an important part of Vermont's
      dairy sector, and this tracks a growing trend of artisan agricultural practice in
      the United States. In popular discourse and academic research into products like
      artisan cheese, consumers explain their preferences in terms of intrinsic sensory
      and extrinsic - supposedly nonsensory - food qualities. In laboratory sensory
      studies, however, the relationship between preference, intrinsic, and extrinsic
      qualities changes or disappears. In contrast, this study explains this
      relationship by adopting a social theory of sensory perception as a practice in
      everyday life. This theory is applied to a series of focus group interviews with
      Vermont artisan cheese consumers about their everyday perceptions. Based on the
      data, a conceptual framework for the sensory perception of Vermont artisan cheese
      is suggested: consumers combine information about producer practice, social
      context, and the materiality of the product through an active, learned practice
      of sensory perception. Particular qualities that drive consumer sensory
      experience and preference are identified from the interview data. Many of these
      qualities are difficult to categorize as entirely intrinsic or extrinsic,
      highlighting the need for developing new approaches of sensory evaluation in
      order to fully capture everyday consumer sensory perception. Thus, this research
      demonstrates that social theory provides new and valuable insights into consumer
      sensory preference for Vermont artisan cheese. 

PMID- 24681406
TI  - Adherence to Mediterranean diet in a Spanish university population.
AB  - The aim of this work was to characterize food habits of Spanish University
      students and to assess the quality of their diet and some possible determinant
      factors according to Mediterranean food pattern among other indices. Two hundred
      eighty-four enrolled students during the academic year 2012-2013 participated in
      this survey. For each individual a questionnaire involving anthropometric
      measurements, types of housing, smoking habits and levels of physical activity
      were self-reported. Food consumption was gathered by two nonconsecutive 24 hour
      recalls including one weekend day. BMI within the normal range was showed by
      72.5% of students and 75% of the sample reflected a sedentary lifestyle or low
      physical activity. The percentage of total energy from each macronutrient was
      approximately 17% proteins, 40% carbohydrates and 40% lipids. The ratio of
      polyunsaturated to monounsaturated fat only reached 0.32. Cholesterol consumption
      in men exceeded the intake in women by 70 mg/day but nutritional objectives were
      exceeded in both genders. The main source of protein had an animal origin from
      meat (38.1%), followed by cereals (19.4%) and dairy products (15.6%). The
      assessment of diet quality conducted by Healthy Eating Index (HEI) and
      Mediterranean Diet Score (MDS) revealed a low-intermediate score in both (51.2 +/
      12.8 and 4.0 +/- 1.5, respectively). The main deviations from Mediterranean
      pattern were a low intake of vegetables and fruit and a high consumption of meat
      and dairy products. According to HEI classification, 96.1% of subjects scored
      "poor" or "needs improvement" about the quality of their diet and only 5.3% of
      students achieved a high adherence to Mediterranean diet. It is necessary to
      foster changes toward a healthier diet pattern according to cultural context in
      this population for preventing cardiovascular diseases, type 2 diabetes and
      insulin resistance.

PMID- 24681407
TI  - Exploring the potential of metallic nanoparticles within synthetic biology.
AB  - The fields of metallic nanoparticle study and synthetic biology have a great deal
      to offer one another. Metallic nanoparticles as a class of material have many
      useful properties. Their small size allows for more points of contact than would
      be the case with a similar bulk compound, making nanoparticles excellent
      candidates for catalysts or for when increased levels of binding are required.
      Some nanoparticles have unique optical qualities, making them well suited as
      sensors, while others display para-magnetism, useful in medical imaging,
      especially by magnetic resonance imaging (MRI). Many of these metallic
      nanoparticles could be used in creating tools for synthetic biology, and
      conversely the use of synthetic biology could itself be utilised to create
      nanoparticle tools. Examples given here include the potential use of quantum dots
      (QDs) and gold nanoparticles as sensing mechanisms in synthetic biology, and the
      use of synthetic biology to create nanoparticle-sensing devices based on current
      methods of detecting metals and metalloids such as arsenate. There are a number
      of organisms which are able to produce a range of metallic nanoparticles
      naturally, such as species of the fungus Phoma which produces anti-microbial
      silver nanoparticles. The biological synthesis of nanoparticles may have many
      advantages over their more traditional industrial synthesis. If the proteins
      involved in biological nanoparticle synthesis can be put into a suitable
      bacterial chassis then they might be manipulated and the pathways engineered in
      order to produce more valuable nanoparticles. 

PMID- 24681408
TI  - Ethanol production from glycerol-containing biodiesel waste by Klebsiella
      variicola shows maximum productivity under alkaline conditions.
AB  - Biodiesel fuel (BDF) waste contains large amounts of crude glycerol as a by
      product, and has a high alkaline pH. With regard to microbial conversion of
      ethanol from BDF-derived glycerol, bacteria that can produce ethanol at alkaline
      pH have not been reported to date. Isolation of bacteria that shows maximum
      productivity under alkaline conditions is essential to effective production of
      ethanol from BDF-derived glycerol. In this study, we isolated the Klebsiella
      variicola TB-83 strain, which demonstrated maximum ethanol productivity at
      alkaline pH. Strain TB-83 showed effective usage of crude glycerol with maximum
      ethanol production at pH 8.0-9.0, and the culture pH was finally neutralized by
      formate, a by-product. In addition, the ethanol productivity of strain TB-83
      under various culture conditions was investigated. Ethanol production was more
      efficient with the addition of yeast extract. Strain TB-83 produced 9.8 g/L
      ethanol (0.86 mol/mol glycerol) from cooking oil-derived BDF waste. Ethanol
      production from cooking oil-derived BDF waste was higher than that of new frying
      oil-derived BDF and pure-glycerol. This is the first report to demonstrate that
      the K. variicola strain TB-83 has the ability to produce ethanol from glycerol at
      alkaline pH.

PMID- 24681409
TI  - In-depth proteomic delineation of the colorectal cancer exoproteome: Mechanistic
      insight and identification of potential biomarkers.
AB  - Systemic mining of cancer exoproteome/secretome has emerged as a pivotal strategy
      for delineation of molecular pathways with mechanistic importance in cancer
      development, as well as the discovery of diagnostic/prognostic biomarkers.
      Although major advances in diagnostic and therapeutic management of colorectal
      cancer have been underscored in the last decade, this cancer still remains the
      second leading cause of cancer-related deaths in the developed world. Despite
      previous studies on deciphering the colorectal cancer exoproteome, such studies
      lack adequate depth and robustness due to technological limitations. Here, using
      a well-established LC-MS/MS method on an LTQ-Orbitrap mass spectrometer, we
      extensively delineated the exoproteome of 12 colon cancer cell lines. In total,
      2979 non-redundant proteins were identified with a minimum of two peptides, of
      which ~62% were extracellular or cell membrane-bound, based on prediction
      software. To further characterize this dataset and identify clinical
      opportunities, first, we investigated overrepresented molecular concepts of
      interest via enrichment map analysis and second, we demonstrated translational
      importance of certain proteins, such as olfactomedin-4 and kallikrein-related
      peptidases-6 and -10, by investigating their expression levels in patient tissues
      and/or fluids. Overall, the present study details a comprehensive colorectal
      cancer exoproteome dataset, and may be used as future platform for biomarker
      discovery, and hypothesis-generating studies. BIOLOGICAL SIGNIFICANCE: This
      article represents one of the most extensive and comprehensive proteomic datasets
      regarding the secreted/extracellular proteome of colorectal cancer cell lines.
      The reported datasets may form a platform for a plethora of future, discovery
      based or hypothesis-generating studies, attempting to either delineate putative
      cancer biomarkers for CRC, or elucidate questions of mechanistic importance (e.g.
      investigation of deregulated pathways for CRC progression).

PMID- 24681410
TI  - Effect of dietary fiber/starch balance on the cecal proteome of growing rabbits.
AB  - Dietary fiber/starch imbalance can lead to diarrhea in rabbits. However, the
      underlying molecular mechanisms are largely unknown, and this is the first study
      on the proteome profile of the cecal tissue of diarrheic rabbits. In this study,
      one group of weanling rabbits was fed a high fiber/starch diet (control group),
      and another group was fed a low fiber/starch diet (diarrhea group). We applied 2
      D gel electrophoresis, coupled with histological and biochemical analyses, to
      study dynamic changes in the proteome of the cecal tissue from healthy and
      diarrheic growing rabbits. We identified 29 protein spots showing differential
      abundance between the two groups. We identified the proteins and found that they
      participated in key biological processes, including absorption, digestion and
      transport; cell structure and motility; inflammatory response; glucose and energy
      metabolism; mineral and vitamin metabolism; stress response and cell redox
      homeostasis. Moreover, the results of our proteomics analysis revealed continuous
      impairment and compensatory intestinal repair in the rabbits with diarrhea.
      Therefore, these findings shed light on the main mechanisms and the main proteins
      involved in intestinal degradation in diarrhea. These findings have important
      implications for understanding the mechanism of cecal damage and repair in
      diarrhea in rabbits caused by dietary factors. BIOLOGICAL SIGNIFICANCE: The
      different cecal protein expressions were compared between healthy and diarrhea in
      growing rabbit model fed different fiber/starch diets. Diarrhea caused by feeding
      high-starch diet induced mucosal injury and inflammation. In this work we
      identify protein spots by MALDI-TOF MS and classify by biological function. The
      finding that the expression of all other proteins belonging to seven functional
      groups was significantly increased in the diarrheic rabbits, except for CMBL,
      suggests that many intestinal functional proteins may be related to up
      regulation, such as cell absorption, digestion, transport, structure, motility,
      metabolism (including energy mineral and vitamin), inflammatory response, stress
      response, and redox homeostasis in diarrhea.

PMID- 24681411
TI  - Current management practice for bladder cancer in Hong Kong: a hospital-based
      cross-sectional survey.
AB  - OBJECTIVES: To examine current practice in the management of bladder cancer in
      Hong Kong government and private hospitals. DESIGN: Cross-sectional survey.
      SETTING: All government hospitals and the major private institutions in Hong
      Kong, which provide urological services. PARTICIPANTS: Urologists responding to
      an anonymous, self-administered, web-based questionnaire regarding practices in
      smoking cessation, treatment of non-muscle invasive bladder cancer and muscle
      invasive bladder cancer, and research into bladder cancer. RESULTS: Of the 29
      urologists from 11 government hospitals and eight private institutions who were
      invited, 18 from 11 (100%) government hospitals and seven from six (75%) private
      institutions responded, which amounted to an 86% response rate. In all, 88% of
      the respondents seldom or never referred their bladder cancer patients to smoking
      cessation programmes. Hong Kong urologists showed good compliance in the
      management of non-muscle invasive bladder cancer according to international
      guidelines. There was great variation with regard to regimens for maintenance of
      intravesical immunotherapy. There was underuse of perioperative systemic
      chemotherapy, despite wide acceptance of this practice; fewer than 10% of the
      patients received neo-adjuvant and adjuvant systemic chemotherapy for the
      treatment of muscle invasive bladder cancer. Of the surveyed urologists, 80%
      expressed an inadequacy of resources for bladder cancer research and 96% agreed
      that a local inter-hospital bladder cancer database was needed. CONCLUSIONS: This
      study demonstrated great diversity in the use of intravesical immunotherapy,
      perioperative systemic chemotherapy, and surgical treatment of bladder cancer
      among urology service providers. There is a need for clear recommendations in
      these areas.

PMID- 24681412
TI  - Double free flaps for reconstruction of complex/composite defects in head and
      neck surgery.
AB  - OBJECTIVE. To demonstrate the feasibility of double free flap surgery in head and
      neck reconstruction. DESIGN. Descriptive case series. SETTING. A university
      affiliated hospital in Hong Kong. PATIENTS. Twelve patients with head and neck
      cancer (encountered over a 2.5-year period) who had reconstructive surgery with
      planned simultaneous double free flaps. RESULTS. The mean total operating time
      was 660 minutes and there were no flap failures. Postoperative stays ranged from
      11 to 82 days; nine patients were discharged within 3 weeks and seven were able
      to maintain their weight with oral feeding. The survival rate up to 1 year was
      64%. CONCLUSION. The use of double free flaps is an option worth considering for
      complex head and neck defects in carefully selected patients. 

PMID- 24681413
TI  - [New ethical issues about pharmaceuticals in Western and Central Africa].

PMID- 24681414
TI  - Synthesis of poly(E-caprolactone) nanospheres in the presence of the protective
      agent poly(glutamic acid) and their cytotoxicity, genotoxicity and ability to
      induce oxidative stress in HepG2 cells.
AB  - Nanospheres of poly(E-caprolactone) (PCL) with sizes smaller than 200 nm were
      produced by combining the freeze drying method and the physicochemical
      solvent/non-solvent approach. The influence of various types of cryoprotectants
      (poly(glutamic acid) (PGA) or sacharose) and their concentrations on the outcome
      of freeze-dried poly(E-caprolactone) particles was evaluated. The physiochemical
      properties, structural and morphological characteristics of thereby obtained PCL
      particles were determined by scanning electron microscopy (SEM) and Fourier
      transform infrared spectroscopy (FTIR). The cytotoxicity of the samples was
      examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay (MTT assay). The formation of intracellular reactive oxygen species was
      measured spectrophotometrically using a fluorescent probe (DCFH-DA assay). In
      addition, the genotoxic response of PCL particles obtained using PGA as a
      cryoprotectant was investigated by the Comet assay. This paper focuses on the
      role of PGA in the synthesis of PCL particles and demonstrates that PGA plays a
      dual role in the synthesis, i.e. it acts as a stabilizer but also as a
      cryoprotective agent. The sufficient and optimal concentration of PGA for
      producing uniform, spherical but also biocompatible PCL nanoparticles is
      established to be 0.05%.

PMID- 24681415
TI  - Relationship of immunologic response to antiretroviral therapy with non-AIDS
      defining cancer incidence.
AB  - OBJECTIVE: To estimate the association between immunologic response to
      antiretroviral therapy (ART) and non-AIDS defining cancer (NADC) incidence in HIV
      infected patients. DESIGN: A prospective cohort including patients with at least
      1 cell/MUl CD4 cell count and HIV-1 RNA measure after ART initiation between 1996
      and 2011 in the Centers for AIDS Research Network of Integrated Clinical Systems,
      a collaboration of eight HIV clinics at major academic medical centres in the
      United States. METHODS: Measures of immunologic response were 6-month CD4 post
      ART, latest CD4 and CD4 count-years, a cumulative measure of CD4 lymphopenia. Cox
      regression with inverse probability-of-exposure weights was used to calculate
      adjusted hazard ratios of virus-related and virus-unrelated NADC incidence.
      RESULTS: Among 9389 patients at ART initiation, median CD4 cell count was 200
      cells/MUl [interquartile range (IQR) 60-332)], and median HIV-1 RNA was 4.8 log10
      copies/ml (IQR 4.3-5.4). Median follow-up was 3.3 years (IQR 1.5-6.5). After 6
      months of ART, median CD4 cell count was 304 cells/MUl (IQR 163-469). One hundred
      and sixty-four NADCs were diagnosed during study follow-up, 65 (40%) considered
      virus-related. Virus-related NADCs were inversely associated with 6-month CD4
      cell count (hazard ratio per 100 cells/MUl increase=0.71), latest CD4 cell count
      (hazard ratio per 100 cells/MUl increase=0.70) and CD4 cell count-years (hazard
      ratio per 200 cell-years/MUl increase=0.91) independent of CD4 cell count at ART
      initiation, age and HIV-1 RNA response. No associations were found with virus
      unrelated NADCs. CONCLUSION: Poor CD4 cell count response was strongly associated
      with virus-related NADC incidence, suggesting an important role for T-cell
      mediated immunity in pathogenesis. Lower CD4 cell count proximal to cancer
      diagnosis may be a result of subclinical cancer. Intensified cancer screening
      should be considered for patients on ART with low CD4 cell counts.

PMID- 24681416
TI  - The undiagnosed HIV epidemic in France and its implications for HIV screening
      strategies.
AB  - BACKGROUND: Describing the undiagnosed HIV-infected population is essential for
      guiding HIV screening policy, implementing interventions, and resource planning.
      METHODS: We used French national HIV surveillance data and a back-calculation
      approach to estimate the number of undiagnosed HIV-infected individuals in France
      and the distribution of time since HIV infection among undiagnosed individuals.
      We also used data on CD4+ cell count decline to assess the CD4+ cell count
      distribution among undiagnosed individuals. RESULTS: We estimated that 29,000
      [95% confidence interval (CI): 24,200-33,900] individuals were living with
      undiagnosed HIV infection at the end of 2010. Of these, 28.7% (95% CI: 27.1-30.4)
      were infected less than a year ago, 16.4% (95% CI: 15.0-17.8) more than 5 years
      ago, and 59.6% (95% CI: 59.2-59.8) were eligible for antiretroviral treatment
      (CD4+ cell count less than 500 cells/MUl) according to the 2010 French
      guidelines. Men represented 70.0% of the undiagnosed HIV-infected individuals and
      had lower CD4+ cell counts than women. The numbers of undiagnosed infections in
      MSM, non-French national heterosexuals, and French national heterosexuals were
      similar (9200, 9300, 10,000, respectively). However, because of differences in
      group size, undiagnosed HIV prevalence varied significantly between these groups
      (2.95, 0.36, 0.03%, respectively; P less than 0.001). CONCLUSION: Our findings
      suggest that many undiagnosed HIV-infected individuals were eligible for
      treatment and, thus, lack of HIV diagnosis is a lost chance for them; many more
      heterosexuals than MSM will need to be tested to find those undiagnosed; and
      universal screening of men may be cost-effective, especially in the areas most
      affected by the epidemic, such as the Paris region.

PMID- 24681418
TI  - Acceptability of Health Care-Related Risks: A Literature Review.
AB  - OBJECTIVES: Risk management aims at reducing risks associated with hospital care
      to an acceptable level, both in their frequency and their impact on health. The
      social acceptability of risk on the part of the general population and of the
      health-care professionals, faced with regular information about adverse events,
      is undoubtedly evolving rapidly.In contrast to risk acceptability, the concept of
      risk perception is of limited interest to risk managers because it does not
      inform on the behaviors and actions resulting from these perceptions. The aim of
      this work was to define the concept of social acceptability of risk through an in
      depth examination of a wide-ranging and multidisciplinary literature. METHODS: A
      1990-2010 English and French literature review was carried out in medical,
      epidemiological, and human and social sciences online databases, gray literature,
      and books. RESULTS: Of the 5931 references retrieved, 203 met the inclusion
      criteria. We identified contributions from 5 major research fields: economic,
      sociocognitive, psychometric, sociological/anthropological, and interactionist.
      When assessing risks, individuals use a variety of psychological and social
      processes that include their perception not only of a given risk but also of
      their own personal and social resources. This global perception has a direct
      impact on the responses and actual behavior of individuals and groups, enabling
      them to cope with the risk and/or manage it. CONCLUSIONS: Social acceptability
      includes perceptions related to risks and the stated intentions of individual
      behavior. This concept may therefore be relevant for defining local and national
      patient safety priorities.

PMID- 24681419
TI  - Commentary on Performance Improvement: One Psychiatry Department's Experience.

PMID- 24681417
TI  - Performance of symptom-based tuberculosis screening among people living with HIV:
      not as great as hoped.
AB  - OBJECTIVE: The objective of the present study was to determine the diagnostic
      performance of the symptom-based tuberculosis (TB) screening questionnaire
      recommended by WHO for people living with HIV (PLWH) in resource-limited
      settings, among adults off and on antiretroviral therapy (ART). DESIGN: Cross
      sectional study at two HIV clinics in South Africa. METHODS: A total of 825 PLWH
      completed the screening questionnaire and underwent investigations [chest
      radiography (CXR) and microbiologic testing of sputa]. A positive screen was
      defined as presence of cough, fever, night sweats, or weight loss. Pulmonary
      tuberculosis (PTB) was defined as sputum smear positive for acid-fast bacilli or
      growth of Mycobacterium tuberculosis. RESULTS: Of 737 participants with at least
      one diagnostic sputum specimen, PTB was diagnosed in 31 of 522 (5.9%) on ART, and
      34 of 215 (15.8%) not on ART. The questionnaire missed 15 of 31 (48.4%) PTB cases
      on ART, and three of 34 (8.8%) not on ART. Among participants on ART, post-test
      probability of PTB diagnosis (95% confidence interval) was 6.8% (4.0-10.9%) if
      screening positive, and 5.2% (2.9-8.4%) if screening negative, whereas among
      participants not on ART, post-test probabilities were 20.3% (14.2-27.5%) and 4.8%
      (1.0-13.5%), respectively. Among participants diagnosed with PTB, those on ART
      were significantly less likely to screen positive (adjusted odds ratio 0.04, 95%
      confidence interval: 0.01-0.39). In both groups (ART and no ART), screening was
      more sensitive when CXR was incorporated. CONCLUSION: For case detection and
      exclusion of PTB, the WHO-recommended questionnaire performed adequately among
      PLWH not on ART, and poorly among those on ART. Further research is needed to
      identify feasible and effective TB screening strategies for PLWH in resource
      limited settings.

PMID- 24681420
TI  - Hidden Barriers to Delivery of Pharmacological Venous Thromboembolism
      Prophylaxis: The Role of Nursing Beliefs and Practices.
AB  - BACKGROUND: Standardized electronic order sets for venous thromboembolism
      prophylaxis have increased the proportion of patients receiving venous
      thromboembolism prophylaxis. However, ordering venous thromboembolism prophylaxis
      does not ensure consistent administration. OBJECTIVE: To explore causes of
      variability in the rate of administration of ordered doses of pharmacological
      venous thromboembolism prophylaxis among hospital units. DESIGN: Mixed methods
      study, including qualitative observation and quantitative nursing survey
      administration. SUBJECTS: Nurses included in observations were practicing on an
      inpatient unit, caring for patients with orders to receive venous thromboembolism
      prophylaxis consisting of low-dose unfractionated heparin or low-molecular weight
      heparin. Nurses on 12 inpatient units with disparate rates of administration were
      included in the survey. MEASURES: Qualitative observation data were collected
      until thematic saturation was achieved. Survey was conducted to identify beliefs
      and practices surrounding nursing administration of venous thromboembolism
      prophylaxis. RESULTS: During observations, some nurses presented pharmacological
      venous thromboembolism prophylaxis to their patients as an optional therapy.
      Nurses on low-performing units are more likely to believe that pharmacological
      venous thromboembolism prophylaxis is ordered for patients who do not require it.
      More often, they also acknowledge that nurses use their clinical decision-making
      skills to determine when to omit unnecessary doses of prescribed venous
      thromboembolism prophylaxis. CONCLUSIONS: Nurses on units with low administration
      rates often believe they have the skills to determine which patients require
      pharmacological venous thromboembolism prophylaxis. They are also more likely to
      believe that ordered doses are discretionary and offer the medication as optional
      to patients.

PMID- 24681421
TI  - Safety Culture in Indian Hospitals: A Cultural Adaptation of the Safety Attitudes
      Questionnaire.
AB  - OBJECTIVES: Patient safety is increasingly recognized as a global health concern
      because of a staggering number of health care-related injuries and deaths.
      Although many hospitals are attempting to promote a patient safety agenda, there
      are relatively few options to track progress. The aims of this study were to
      translate and culturally adapt the Safety Attitudes Questionnaire (SAQ) into
      Gujarati and to provide evidence for its reliability and validity in hospitals in
      Gujarat, India. We also present preliminary data on the safety culture in these
      organizations. METHODS: The first phase was the cultural adaptation and
      translation of the SAQ into Gujarati. The second phase was a cross-sectional
      survey of safety attitudes in 4 private hospitals. RESULTS: The survey was
      distributed to 424 health care workers and elicited an overall response rate of
      79%. The questionnaire showed acceptable reliability and preliminary evidence for
      construct validity among health care workers in 4 private hospitals of varying
      size. The initial culture score results showed outcomes similar to international
      standards, with two-thirds of the respondents describing teamwork climate
      positively and more than half of the respondents describing safety climate
      positively. CONCLUSIONS: This study reveals promising initial results for patient
      safety culture in India, but further study is needed. The development and
      validation of the SAQ-Gujarati allow additional hospitals to evaluate their
      patient safety culture. As the first rendition of the SAQ to an Indian setting,
      the tool could help to initiate safety discourse and improve the potential for
      institutions to provide feedback to their staff members.

PMID- 24681422
TI  - State-Mandated Hospital Infection Reporting Is Not Associated With Decreased
      Pediatric Health Care-Associated Infections.
AB  - OBJECTIVES: State governments increasingly mandate public reporting of central
      line-associated blood stream infections (CLABSIs). This study tests if hospitals
      located in states with state-mandated, facility-identified, pediatric-specific
      public CLABSI reporting have lower rates of CLABSIs as defined by the Agency for
      Healthcare Research and Quality's Pediatric Quality Indicator 12 (PDI12).
      METHODS: Utilizing the Kids' Inpatient Databases from 2000 to 2009, we compared
      changes in PDI12 rates across three groups of states: states with public CLABSI
      reporting begun by 2006, states with public reporting begun by 2009 and never
      reporting states. In the baseline period (2000-2003), no states mandated public
      CLABSI reporting. A multivariable, hospital-level random intercept, logistic
      regression was performed comparing changes in PDI12 rates in states with public
      reporting to changes in PDI12 rates in never-reporting states. RESULTS: 4,705,857
      discharge records were eligible for PDI12. PDI12 rates significantly decreased in
      all reporting groups, comparing baseline to the post-public reporting period
      (2009): Never Reporters 88% decrease (95% CI, 86%-89%), Reporting Begun by 2006
      90% decrease (95% CI, 83%-94%), and Reporting Begun by 2009 74% decrease (95% CI,
      72%-76%). The Never Reporting Group had comparable decreases in PDI12 rates to
      the Reporting Begun by 2006 group (P = 0.4) and significantly larger decreases in
      PDI12 rates compared to the Reporting Begun by 2009 group (P < 0.001), despite
      having no states with public reporting. CONCLUSIONS: Public CLABSI reporting
      alone appears to be insufficient to affect administrative data-based measures of
      pediatric CLABSI rates or children may be inadequately targeted in current public
      reporting efforts.

PMID- 24681423
TI  - Is age a factor in the success or failure of remote monitoring in heart failure?
      Telemonitoring and structured telephone support in elderly heart failure
      patients.
AB  - BACKGROUND: There are few data regarding the effectiveness of remote monitoring
      for older people with heart failure. We conducted a post-hoc sub-analysis of a
      previously published large Cochrane systematic review and meta-analysis of
      relevant randomized controlled trials to determine whether structured telephone
      support and telemonitoring were effective in this population. METHODS: A post hoc
      sub-analysis of a systematic review and meta-analysis that applied the Cochrane
      methodology was conducted. Meta-analyses of all-cause mortality, all-cause
      hospitalizations and heart failure-related hospitalizations were performed for
      studies where the mean or median age of participants was 70 or more years.
      RESULTS: The mean or median age of participants was 70 or more years in eight of
      the 16 (n=2659/5613; 47%) structured telephone support studies and four of the 11
      (n=894/2710; 33%) telemonitoring studies. Structured telephone support (RR 0.80;
      95% CI=0.63-1.00) and telemonitoring (RR 0.56; 95% CI=0.41-0.76) interventions
      reduced mortality. Structured telephone support interventions reduced heart
      failure-related hospitalizations (RR 0.81; 95% CI=0.67-0.99). CONCLUSION: Despite
      a systematic bias towards recruitment of individuals younger than the
      epidemiological average into the randomized controlled trials, older people with
      heart failure did benefit from structured telephone support and telemonitoring.
      These post-hoc sub-analysis results were similar to overall effects observed in
      the main meta-analysis. While further research is required to confirm these
      observational findings, the evidence at hand indicates that discrimination by age
      alone may be not be appropriate when inviting participation in a remote
      monitoring service for heart failure.

PMID- 24681425
TI  - Pericytes prevent regression of endothelial cell tubes by accelerating metabolism
      of lysophosphatidic acid.
AB  - Efforts to eradicate pathological vessels in neovascular diseases and induce
      growth of mature, functional vasculature in ischemic diseases are limited by our
      incomplete understanding of molecular mechanisms of vessel stabilization. While
      it is well known that pericytes stabilize blood vessels, the underlying
      mechanisms have not been fully elucidated. The goal of this study was to further
      investigate the mechanisms by which pericytes stabilize vessels. In an in vitro
      model of blood vessels, in which regression is driven by lysophosphatidic acid
      (LPA), pericyte-mediated stabilization was associated with a decrease in the
      concentration of LPA. The decline in the concentration of LPA was not caused by a
      reduction in activity or expression of autotaxin, the main enzyme implicated in
      LPA production. Rather, pericytes accelerated LPA metabolism. Stabilization of
      tubes by pericytes correlated with accelerated LPA dephosphorylation and
      increased expression of lipid phosphate phosphatases (LPPs). Finally, pericytes
      failed to stabilize tubes exposed to an LPA analogue, which was resistant to
      degradation. Our results suggest that pericytes stabilize endothelial cell tubes
      by accelerating the metabolism of LPA. 

PMID- 24681424
TI  - Sp1 modification of human endothelial nitric oxide synthase promoter increases
      the hypoxia-stimulated activity.
AB  - Human endothelial nitric oxide synthase (eNOS) gene has a TATA-less weak promoter
      with a low activity. The aim of this study was to increase eNOS promoter activity
      by modification. Human eNOS promoter was modified by inserting a Sp1 element at a
      -74 bp site and function of the modified promoter was investigated via a hypoxia
      model induced by cobalt chloride in human umbilical vein endothelial cells. The
      results demonstrated that the Sp1-modified promoter resulted in a significant
      increase of normalized luciferase activity in the presence of hypoxia. There was
      a correlation between the transcriptional activity of the Sp1-modified promoter
      and the level of eNOS expression with enhancement of nitric oxide production.
      Together, these data indicate that human eNOS promoter activity is increased by
      inserting Sp1 binding site into the GC-rich region of the promoter in response to
      hypoxia, suggesting that this provides an approach to ameliorate microcirculation
      barrier of some cardiovascular disease and to study its mechanistic process.

PMID- 24681426
TI  - A uniform graphical representation of intensity coding in current-generation
      cochlear implant systems.
AB  - OBJECTIVES: Understanding and predicting the impact of MAP changes on the
      electrical current delivered at the level of cochlear implant (CI) electrodes is
      challenging. However, it is an important prerequisite for effectively programming
      these devices in clinical practice. This article describes a graphical
      representation to illustrate the intensity-coding behavior of four CI systems
      (Cochlear, MED-EL, Advanced Bionics, and Neurelec). DESIGN: For this the authors
      have broken down the intensity coding into two separate transformations: (1) from
      broadband acoustical input to band limited channel amplitude and (2) the mapping
      function within a single channel. These functions have been synthesized and
      presented in a uniform plot across brands. RESULTS: The plot describes the output
      of a CI channel in response to different input signals. This has been
      incorporated in an interactive software application that illustrates the
      different stages of intensity coding and the impact of the relevant fitting
      parameters for each CI brand. CONCLUSIONS: The plot provides the clinician with
      an assistive tool to better understand and predict the behavior of CIs, which may
      lead to more knowledgeable interpretation and CI programming.

PMID- 24681427
TI  - Solid phase extraction of radioyttrium from irradiated strontium target using
      nanostructure ion imprinted polymer formed with 1-hydroxy-4-(prop-2-enyloxy)-9,10
      anthraquinone.
AB  - A new complex of 1-hydroxy-4-(prop-2-enyloxy)-9,10-anthraquinone and Y(III) was
      synthesized and used as the functional monomer for a novel Y(III) nanostructure
      ion-imprinted polymer. This polymer was used as a sorbent for fast and selective
      separation. The separation method was based on radioyttrium sorption from aqueous
      HCl solution containing strontium onto ion-imprinted polymer. Influence of
      various parameters such as pH, mass sorbent, nature, concentration and volume of
      eluent was investigated. The radioyttrium recovery yield was 99.8% and Sr content
      was estimated to be 3 ug mL(-1).

PMID- 24681428
TI  - Determination of age specific 131I S-factor values for thyroid using
      anthropomorphic phantom in Geant4 simulations.
AB  - Using anthropomorphic phantom in Geant4, determination of beta- and gamma
      absorbed fractions and energy absorbed per event due to (131)I activity in
      thyroid of individuals of various age groups and geometrical models, have been
      carried out. In the case of (131)I beta-particles, the values of the absorbed
      fraction increased from 0.88 to 0.97 with fetus age. The maximum difference in
      absorbed energy per decay for soft tissue and water is 7.2% for gamma-rays and
      0.4% for beta-particles. The new mathematical MIRD embedded in Geant4 (MEG) and
      two-lobe ellipsoidal models developed in this work have 4.3% and 2.9% lower value
      of S-factor as compared with the ORNL data.

PMID- 24681429
TI  - Stable isotope analysis of the karst hydrological systems in the Bay of Kvarner
      (Croatia).
AB  - Here we present the results of the first systematic analysis of the stable
      isotope composition of the karst hydrological systems in the Bay of Kvarner.
      Gaussian mixture modelling, time series analysis and autoregressive integrated
      moving average (ARIMA) modelling were applied using the stable isotope
      compositions of the karst groundwater. This study revealed that the recharge is
      dominated by winter precipitation, the dual-porosity system is dominated by
      baseflow, the hinterlands of the individual springs have different degrees of
      karstification and the springs within the Rjecina River catchment have higher
      recharge elevations than the springs in the Bakar Bay catchment. 

PMID- 24681430
TI  - Non-contact video-based vital sign monitoring using ambient light and auto
      regressive models.
AB  - Remote sensing of the reflectance photoplethysmogram using a video camera
      typically positioned 1 m away from the patient's face is a promising method for
      monitoring the vital signs of patients without attaching any electrodes or
      sensors to them. Most of the papers in the literature on non-contact vital sign
      monitoring report results on human volunteers in controlled environments. We have
      been able to obtain estimates of heart rate and respiratory rate and preliminary
      results on changes in oxygen saturation from double-monitored patients undergoing
      haemodialysis in the Oxford Kidney Unit. To achieve this, we have devised a novel
      method of cancelling out aliased frequency components caused by artificial light
      flicker, using auto-regressive (AR) modelling and pole cancellation. Secondly, we
      have been able to construct accurate maps of the spatial distribution of heart
      rate and respiratory rate information from the coefficients of the AR model. In
      stable sections with minimal patient motion, the mean absolute error between the
      camera-derived estimate of heart rate and the reference value from a pulse
      oximeter is similar to the mean absolute error between two pulse oximeter
      measurements at different sites (finger and earlobe). The activities of daily
      living affect the respiratory rate, but the camera-derived estimates of this
      parameter are at least as accurate as those derived from a thoracic expansion
      sensor (chest belt). During a period of obstructive sleep apnoea, we tracked
      changes in oxygen saturation using the ratio of normalized reflectance changes in
      two colour channels (red and blue), but this required calibration against the
      reference data from a pulse oximeter. 

PMID- 24681431
TI  - The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness.
AB  - Different approaches have been followed to characterize the role of 5
      hydroxytryptamine (serotonin) receptor 7 (5-HT7) in the regulation of sleep-wake
      behavior: (1) 5-HT7 receptor knockout mice spend less time in rapid eye movement
      sleep than their wild-type counterparts, mainly during the light period. In
      contrast, there is no difference between the genotypes in time spent in
      wakefulness or slow-wave sleep. (2) Systemic administration of the selective 5
      HT7 receptor agonist LP-211 significantly increased wakefulness (time spent
      awake) and reduced rapid eye movement sleep in the rat. Direct infusion of LP-211
      into the dorsal raphe nucleus, locus coeruleus nucleus, basal forebrain
      (horizontal limb of the diagonal band of Broca), or laterodorsal tegmental
      nucleus also produced a decrease in rapid eye movement sleep. Additionally,
      microinjection of the 5-HT7 receptor agonist into the basal forebrain augmented
      the time animals remained awake. Local injection of the 5-HT7 receptor agonist LP
      44 into the dorsal raphe nucleus also suppressed rapid eye movement sleep in the
      rat. (3) A similar reduction of rapid eye movement sleep has been described
      following intraperitoneal injection of the selective 5-HT7 receptor antagonists
      SB-269970 and SB-656104 in the rat and oral administration of the 5-HT7 receptor
      antagonist NJ-18038683 to rat and man. Local microinjection of SB-269970 into the
      dorsal raphe nucleus and basal forebrain also induced a decrease in rapid eye
      movement sleep in the rat. This tends to suggest that the on-off
      (activation/blockade), two-state ligand-receptor interaction model is not tenable
      for the 5-HT7 receptor.

PMID- 24681432
TI  - Frequent methylation of HOXA9 gene in tumor tissues and plasma samples from human
      hepatocellular carcinomas.
AB  - BACKGROUND: Aberrant DNA methylation is associated with the development of
      hepatocellular carcinoma (HCC), suggesting that gene methylation could be a
      potential biomarker for detection of HCC. The aim of this study is to identify
      potential biomarkers in HCC. METHODS: We used the Infinium methylation array and
      a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC.
      Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9
      (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor
      tissues and in 74 plasma samples, including 40 patients with HCC. RESULTS: Ten
      genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and
      CACNA1G) showed differences in methylation between controls and HCCs. Of these,
      HOXA9 was significantly hypermethylated in HCCs (76.7%; 23/30) compared with
      controls (3.4%; 1/29). In addition, combination analysis of two- and three-gene
      sets for HCC detection showed greater sensitivity (90%-96.7%) and comparable
      specificity (93.1%-96.6%) to each individual gene (33.3%-76.7% and 55.2%-100.0%).
      HOXA9 methylation was further validated by Q-MSP in two independent set of
      clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9
      methylation could be detected in plasma from HCC patients (n=40) but not in
      normal plasma (n=34) (p<0.0005). Combined testing (either parameter positive) for
      alpha-fetoprotein (AFP, a plasma protein biomarker) and HOXA9 methylation showed
      greater sensitivity (94.6%) for detection of HCC than AFP alone (75.7%).
      CONCLUSIONS: These data suggest that methylation of HOXA9 could be a helpful
      biomarker to assist in HCC detection.

PMID- 24681433
TI  - System accuracy evaluation of systems for point-of-care testing of blood glucose:
      a comparison of a patient-use system with six professional-use systems.
AB  - BACKGROUND: Point-of-care testing (POCT) of blood glucose (BG) is performed by
      medical personnel in clinical settings as well as by patients themselves for self
      monitoring of blood glucose (SMBG) at home. We investigated if a system mainly
      intended for SMBG by people with diabetes, but also suitable for BG measurements
      by medical personnel, can achieve measurement accuracy on capillary blood samples
      comparable with professional-use POCT systems. METHODS: System accuracy was
      evaluated under standardised conditions, following the ISO standard 15197:2003.
      For each system (one SMBG system with three test strip lots and six professional
      use systems), measurement results from capillary blood samples of 100 subjects
      were compared with a standardised laboratory glucose oxidase method (YSI 2300
      glucose analyser). RESULTS: The seven evaluated systems showed 99.5% or 100% of
      the measurement results within the required system accuracy limits of ISO
      15197:2003 (+/-0.83 mmol/L at BG concentrations <4.2 mmol/L and +/-20% at BG
      concentrations >=4.2 mmol/L). Applying the more stringent requirements of the
      revision ISO 15197:2013, the systems showed between 99% and 100% of the
      measurement results within the accuracy limits (+/-0.83 mmol/L at BG
      concentrations <5.55 mmol/L and +/-15% at BG concentrations >=5.55 mmol/L) and
      between 82% and 98% when even more restrictive limits were applied (+/-0.56
      mmol/L and +/-10%, respectively). CONCLUSIONS: Data from this study, which
      focused on system accuracy, suggest that SMBG systems can achieve system accuracy
      that is comparable with professional-use systems when measurements are performed
      on capillary blood samples by trained personnel in a standardised and controlled
      setting.

PMID- 24681435
TI  - Task preparation and neural activation in stimulus-specific brain regions: an
      fMRI study with the cued task-switching paradigm.
AB  - To investigate the role of posterior brain regions related to task-relevant
      stimulus processing in task preparation, we used a cued task-switching paradigm
      in which a pre-cue informed participants about the upcoming task on a trial: face
      discrimination or number comparison. Employing an event-related fMRI design, we
      examined for changes of activity in face- and number-related posterior brain
      regions (right fusiform face area (FFA) and right intraparietal sulcus (IPSnum),
      respectively), and explored the functional connectivity of these areas with other
      brain regions, during the (preparation) interval between cue onset and onset of
      the (to-be-responded) target stimulus. The results revealed task-relevant
      posterior brain regions to be modulated during this period: activation in task
      relevant stimulus-specific regions was selectively enhanced and their functional
      connectivity to task-relevant anterior brain regions strengthened (right FFA -
      face task, right IPSnum - number task) while participants prepared for the cued
      task. Additionally, activity in task-relevant posterior brain regions was
      influenced by residual activation from the preceding trial in the right FFA and
      the right IPSnum, respectively. These findings indicate that, during task
      preparation, the activation pattern in currently task-relevant posterior brain
      regions is shaped by residual activation as well as preparatory modulation prior
      to the onset of the critical stimulus, even without participants being instructed
      to imagine the stimulus. 

PMID- 24681434
TI  - A Major Facilitator Superfamily protein encoded by TcMucK gene is not required
      for cuticle pigmentation, growth and development in Tribolium castaneum.
AB  - Insect cuticle pigmentation and sclerotization (tanning) are vital physiological
      processes for insect growth, development and survival. We have previously
      identified several colorless precursor molecules as well as enzymes involved in
      their biosynthesis and processing to yield the mature intensely colored body
      cuticle pigments. A recent study indicated that the Bombyx mori (silkmoth) gene,
      BmMucK, which encodes a protein orthologous to a Culex pipiens quiquefasciatus
      (Southern house mosquito) cis,cis, muconate transporter, is a member of the
      "Major Facilitator Superfamily" (MFS) of transporter proteins and is associated
      with the appearance of pigmented body segments of naturally occurring body color
      mutants of B. mori. While RNA interference of the BmMucK gene failed to result in
      any observable phenotype, RNAi using a dsRNA for an orthologous gene from the red
      flour beetle, Tribolium castaneum, was reported to result in molting defects and
      darkening of the cuticle and some body parts, leading to the suggestion that
      orthologs of MucK genes may differ in their functions among insects. To verify
      the role and essentiality of the ortholog of this gene in development and body
      pigmentation function in T. castaneum we obtained cDNAs for the orthologous gene
      (TcMucK) from RNA isolated from the GA-1 wild-type strain of T. castaneum. The
      sequence of a 1524 nucleotides-long cDNA for TcMucK which encodes the putatively
      full-length protein, was assembled from two overlapping RT-PCR fragments and the
      expression profile of this gene during development was analyzed by real-time PCR.
      This cDNA encodes a 55.8 kDa protein consisting of 507 amino acid residues and
      includes 11 putative transmembrane segments. Transcripts of TcMucK were detected
      throughout all of the developmental stages analyzed. The function of this gene
      was explored by injection of two different double-stranded RNAs targeting
      different regions of the TcMucK gene (dsTcMucKs) into young larvae to down
      regulate transcripts during subsequent stages of insect development until the
      adult stage. RNA interference of TcMucK had no observable effects on larval,
      pupal or adult pigmentation. In addition, it did not affect larval-larval, larval
      pupal and pupal-adult molting or survival. Thus, in contrast to the results of
      Zhao et al. (2012), our study demonstrates that TcMucK is not essential for
      growth, development or cuticle pigmentation of T. castaneum. 

PMID- 24681437
TI  - Plant peptides in defense and signaling.
AB  - This review focuses on plant peptides involved in defense against pathogen
      infection and those involved in the regulation of growth and development. Defense
      peptides, defensins, cyclotides and anti-microbial peptides are compared and
      contrasted. Signaling peptides are classified according to their major sites of
      activity. Finally, a network approach to creating an interactomic peptide map is
      described. 

PMID- 24681436
TI  - The hypotensive effect of intrathecally injected (m)VD-hemopressin(alpha) in
      urethane-anesthetized rats.
AB  - Previous studies suggest that cannabinoids system plays an important role in
      cardiovascular regulation. (m)VD-hemopressin(alpha) (VD-Hpalpha), an 11-residue
      peptide originating from the alpha1 chain of hemoglobin, was recently reported as
      a selective agonist of cannabinoid CB1 receptor. The present study was undertaken
      to investigate the intrathecal (i.t.) action of (m)VD-Hpalpha on blood pressure
      in urethane-anesthetized rats. Our results demonstrated that injections of (m)VD
      Hpalpha (5-30 nmol, i.t.) produced a dose-dependent decrease in mean arterial
      pressure (MAP), similar to that of the non-peptidic cannabinoid receptor agonist
      WIN55212-2 (1.25-10 nmol, i.t.). The hypotensive effect of (m)VD-Hpalpha was not
      influenced by the CB1 receptor antagonist AM251 (20 nmol, i.t.) or the CB2
      receptor antagonist AM630 (20 nmol, i.t.). However, WIN55212-2-induced
      hypotension was almost completely prevented by i.t. administration of AM251, not
      by AM630. The spinal hypotension of (m)VD-Hpalpha and WIN55212-2 was
      significantly reduced by pretreatment with the alpha-adrenoceptor antagonist
      phentolamine (1 mg/kg, i.v.), but not by the beta-adrenoceptor antagonist
      propranolol (2 mg/kg, i.v.) or the muscarinic receptor antagonist atropine (2
      mg/kg, i.v.). In addition, L-NAME (50 mg/kg, i.v.), the inhibitor of nitric oxide
      (NO) synthase, significantly reduced WIN55212-2-induced hypotension, but had no
      effect on the hypotensive response to (m)VD-Hpalpha. Collectively, the results
      show that i.t. administration of (m)VD-Hpalpha induces a decrease in MAP via a
      non-CB1 and non-CB2 mechanism.

PMID- 24681438
TI  - A simple-rapid method to separate uranium, thorium, and protactinium for U-series
      age-dating of materials.
AB  - Uranium-series dating techniques require the isolation of radionuclides in high
      yields and in fractions free of impurities. Within this context, we describe a
      novel-rapid method for the separation and purification of U, Th, and Pa. The
      method takes advantage of differences in the chemistry of U, Th, and Pa,
      utilizing a commercially-available extraction chromatographic resin (TEVA) and
      standard reagents. The elution behavior of U, Th, and Pa were optimized using
      liquid scintillation counting techniques and fractional purity was evaluated by
      alpha-spectrometry. The overall method was further assessed by isotope dilution
      alpha-spectrometry for the preliminary age determination of an ancient carbonate
      sample obtained from the Lake Bonneville site in western Utah (United States).
      Preliminary evaluations of the method produced elemental purity of greater than
      99.99% and radiochemical recoveries exceeding 90% for U and Th and 85% for Pa.
      Excellent purity and yields (76% for U, 96% for Th and 55% for Pa) were also
      obtained for the analysis of the carbonate samples and the preliminary Pa and Th
      ages of about 39,000 years before present are consistent with (14)C-derived age
      of the material. 

PMID- 24681439
TI  - Biochemical systems approaches for the analysis of histone modification readout.
AB  - Chromatin is the macromolecular nucleoprotein complex that governs the
      organization of genetic material in the nucleus of eukaryotic cells. In
      chromatin, DNA is packed with histone proteins into nucleosomes. Core histones
      are prototypes of hyper-modified proteins, being decorated by a large number of
      site-specific reversible and irreversible post-translational modifications
      (PTMs), which contribute to the maintenance and modulation of chromatin
      plasticity, gene activation, and a variety of other biological processes and
      disease states. The observations of the variety, frequency and co-occurrence of
      histone modifications in distinct patterns at specific genomic loci have led to
      the idea that hPTMs can create a molecular barcode, read by effector proteins
      that translate it into a specific transcriptional state, or process, on the
      underlying DNA. However, despite the fact that this histone-code hypothesis was
      proposed more than 10 years ago, the molecular details of its working mechanisms
      are only partially characterized. In particular, two questions deserve specific
      investigation: how the different modifications associate and synergize into
      patterns and how these PTM configurations are read and translated by multi
      protein complexes into a specific functional outcome on the genome. Mass
      spectrometry (MS) has emerged as a versatile tool to investigate chromatin
      biology, useful for both identifying and validating hPTMs, and to dissect the
      molecular determinants of histone modification readout systems. We review here
      the MS techniques and the proteomics methods that have been developed to address
      these fundamental questions in epigenetics research, emphasizing approaches based
      on the proteomic dissection of distinct native chromatin regions, with a critical
      evaluation of their present challenges and future potential. This article is part
      of a Special Issue entitled: Molecular mechanisms of histone modification
      function.

PMID- 24681440
TI  - Myc and mRNA capping.
AB  - c-Myc is upregulated in response to growth factors and transmits the signal to
      proliferate by altering the gene expression landscape. When genetic alterations
      result in growth factor-independent c-Myc expression, it can become an oncogene.
      The majority of human tumour types exhibit a degree of c-Myc deregulation,
      resulting in unrestrained cell proliferation. c-Myc binds proximal to the
      promoter region of genes and recruits co-factors including histone
      acetyltransferases and RNA pol II kinases, which promote transcription. c-Myc
      also promotes formation of the cap structure at the 5' end of mRNA. The cap is 7
      methylguanosine linked to the first transcribed nucleotide of RNA pol II
      transcripts via a 5' to 5' triphosphate bridge. The cap is added to the first
      transcribed nucleotide by the capping enzymes, RNGTT and RNMT-RAM. During the
      early stages of transcription, the capping enzymes are recruited to RNA pol II
      phosphorylated on Serine-5 of the C-terminal domain. The mRNA cap protects
      transcripts from degradation during transcription and recruits factors which
      promote RNA processing including, splicing, export and translation initiation.
      The proportion of transcripts with a cap structure is increased by elevating c
      Myc expression, resulting in increased rates of translation. c-Myc promotes
      capping by promoting RNA pol II phosphorylation and by upregulating the enzyme
      SAHH which neutralises the inhibitory bi-product of methylation reactions, SAH. c
      Myc-induced capping is required for c-Myc-dependent gene expression and cell
      proliferation. Targeting capping may represent a new therapeutic opportunity to
      inhibit c-Myc function in tumours. This article is part of a Special Issue
      entitled: Myc proteins in cell biology and pathology. 

PMID- 24681441
TI  - Analysis of perfusates during hypothermic machine perfusion by NMR spectroscopy:
      a potential tool for predicting kidney graft outcome.
AB  - BACKGROUND: Machine perfusion use has been reported to promote graft outcome in
      case of donation after cardiac death. Our objective was to evaluate the potential
      for nuclear magnetic resonance (NMR) to predict graft outcome by analyzing
      perfusates during machine perfusion time. METHOD: We used a renal
      autotransplantation model mimicking deceased after cardiac death donors with
      pigs. Organs were subjected to 60 min of warm ischemia before the hypothermic
      machine preservation during 22 hr. We studied the correlation between creatinemia
      after transplantation and the NMR data from perfusates. RESULTS: A metabonomic
      analysis allowed us to highlight the evolution of several metabolites during
      perfusion: the concentration of lactate, choline, or amino acids such as valine,
      glycine, or glutamate increased with time, whereas there was a diminution of
      total glutathione during this period. The changes in these biomarkers were less
      severe in the group with the better outcome. Statistical analysis revealed a
      strong association between the level of those metabolites during machine
      perfusion and function recovery (Spearman rank >=0.89; P<0.05). CONCLUSION:
      Multivariate analysis of lesion biomarkers during kidney perfusion using NMR data
      could be an interesting tool to assess graft quality, particularly because
      analyses times (2 hr total) are compatible with clinical application.

PMID- 24681442
TI  - Reduction of heavy metals in residues from the dismantling of waste electrical
      and electronic equipment before incineration.
AB  - Residues disposal from the dismantling of waste electrical and electronic
      equipment are challenging because of the large waste volumes, degradation
      resistance, low density and high heavy metal content. Incineration is
      advantageous for treating these residues but high heavy metal contents may exist
      in incinerator input and output streams. We have developed and studied a
      specialized heavy metal reduction process, which includes sieving and washing for
      treating residues before incineration. The preferable screen aperture for sieving
      was found to be 2.36mm (8 meshes) in this study; using this screen aperture
      resulted in the removal of approximately 47.2% Cu, 65.9% Zn, 26.5% Pb, 55.4% Ni
      and 58.8% Cd from the residues. Subsequent washing further reduces the heavy
      metal content in the residues larger than 2.36mm, with preferable conditions
      being 400rpm rotation speed, 5min washing duration and liquid-to-solid ratio of
      25:1. The highest cumulative removal efficiencies of Cu, Zn, Pb, Ni and Cd after
      sieving and washing reached 81.1%, 61.4%, 75.8%, 97.2% and 72.7%, respectively.
      The combined sieving and washing process is environmentally friendly, can be used
      for the removal of heavy metals from the residues and has benefits in terms of
      heavy metal recycling. 

PMID- 24681443
TI  - Accelerated removal of pyrene and benzo[a]pyrene in freshwater sediments with
      amendment of cyanobacteria-derived organic matter.
AB  - The removal of pyrene and benzo[a]pyrene (BaP) were investigated in freshwater
      sediments with amendment of seven different organic matters including
      cyanobacteria-derived organic matter (COM), plant-derived organic matter (POM),
      and humic substances (HS). During the 210 days of experiments, the amendment of
      COM or HS enhanced significantly the removal of pyrene and BaP in sediments,
      especially with fresh COM (FCOM) treatment much superior to HS. On the contrary,
      degradation of these polycyclic aromatic hydrocarbons (PAHs) was not
      significantly improved and even inhibited in POM-amended sediments. The first
      order rate constants of pyrene and BaP degradation in the FCOM-amended sediments
      reached 0.00540+/-0.00017d(-1) and 0.00517+/-0.00057d(-1), respectively, and were
      about three and five folds of those in the control treatment. The enhanced PAHs
      degradation in FCOM-amended sediments was related to higher PAH-degrading
      bacteria number and bioavailability with a result of biostimulation and priming
      effect by labile carbon and high-value nutrition in FCOM. Thus, this study
      improved our understanding about effects of settled biomass from cyanobacterial
      blooms, which occurred frequently in eutrophic aquatic ecosystems, on the natural
      attenuation of PAHs in sediments. Furthermore, this study would also help develop
      a new promising approach to remediate PAH-contaminated sediments through
      utilization of cyanobacterial bloom biomass. 

PMID- 24681444
TI  - Comparative simulation of pneumococcal serogroup 19 polysaccharide repeating
      units with two carbohydrate force fields.
AB  - Streptococcus pneumoniae causes meningitis, pneumonia and severe invasive disease
      (IPD) in young children. Although widespread infant immunisation with the PCV7
      seven-valent pneumococcal conjugate vaccine has led to a dramatic decrease in
      IPD, infections due to non-vaccine serotypes, particularly serotype 19A, have
      increased. As the 19F polysaccharide differs from 19A at a single linkage
      position, it was assumed that PCV7 (containing 19F) would cross-protect against
      19A disease. However, vaccination with PCV7 results in only 26% effectiveness
      against IPD caused by 19A. We explored the conformations and dynamics of the
      polysaccharide repeating units from serotypes 19F and 19A, comparing free energy
      surfaces for glycosidic linkages with 100ns aqueous molecular dynamics
      simulations of the di- and trisaccharide components. All calculations were
      performed with both the CHARMM and the GLYCAM carbohydrate force fields to
      establish whether the choice of model affects the predicted molecular behaviour.
      Although we identified key differences between the force fields, overall they
      were in agreement in predicting a 19F repeating unit with a wider range of
      conformation families than the more restricted 19A trisaccharide. This suggests a
      probable conformational difference between the 19F and 19A polysaccharides, which
      may explain the low cross-protection of 19F vaccines against 19A disease. 

PMID- 24681445
TI  - Negative impact of a cadmium concentration considered environmentally safe in
      Brazil on the cardiac performance of bullfrog tadpoles.
AB  - A drastic amphibian decline has been observed worldwide, which can be attributed
      (among other factors) to exposure to pollutants. Considering that cadmium
      corresponds to the most rapidly increasing trace metal in the environment, the
      aim of this work was to evaluate whether the exposure (2 and 16 days) of bullfrog
      tadpoles to this trace metal, at the concentration currently considered
      environmentally safe (at 1ppb) in class 1 and 2 waters by the Brazilian
      Environmental Council, can affect the cardiac performance of these animals. The
      acute exposure (2 days) of tadpoles to cadmium resulted in a marked bradycardic
      response, which was correlated with an incomplete cardiac relaxation, without any
      compensation by improved cardiac twitch force (Fc) or contraction velocity (TPT),
      nor even by cardiac hypertrophy. Indeed, after 16 days of exposure, the cardiac
      function of tadpoles became even more depressed due to a marked decrease in Fc, a
      prolongation of TPT, and also incomplete relaxation (i.e. increases in the
      ventricle resting tension), without changes in ventricle relative mass.
      Altogether, the cardiodepressive effects of cadmium (especially after more
      prolonged exposure periods) impose negative alterations on a tadpole's
      development and also impede adequate homeostatic adjustments to respond
      appropriately to the exposure to cadmium with increase in energetic demand to
      counteract the deleterious effects of the xenobiotic. These disturbances can
      impair tadpoles' growth, development and reproduction. It is a fact that allows
      us to strongly suggest that cadmium concentrations, which are currently
      considered environmentally safe in Brazil, should be revised. 

PMID- 24681446
TI  - Effects of lead uptake on microtubule cytoskeleton organization and cell
      viability in the seagrass Cymodocea nodosa.
AB  - The effects of lead uptake on microtubule integrity and cell viability in
      intermediate-juvenile leaf blades of the seagrass Cymodocea nodosa were
      investigated under laboratory conditions in increasing exposure concentrations
      (0.1, 0.25, 0.5, 5, 10, 20 and 40mg/L). Uptake kinetics was generally fitted well
      to the Michaelis-Menten equation. The equilibrium concentration and the velocity
      of lead uptake tended to increase as the exposure concentration increased up to 5
      10mg/L; equilibrium concentration values at most of the treatments were
      comparable to reported lead concentrations in seagrass leaves. Lead caused a
      drastic change in the microtubule organization; microtubule depolymerization was
      observed after 3-7 days of exposure, depending on metal dosage. This observation
      indicates that microtubule integrity could be utilized as an early biomarker of
      emerging lead contamination. Cell death starting to occur at later time than
      microtubule disturbance was also observed at all of the treatments. Microtubule
      depolymerization expressed as percentage of fluorescence intensity reduction and
      cell mortality expressed as percentage of dead cells (blue stained) increased
      with time. Toxic effects were first detected during or at the beginning of the
      steady state-phase of lead uptake. The lowest experimental tissue lead
      concentrations associated with the onset of toxic effects (18.33-20.24MUg/g dry
      wt, 0.1-0.25mg/L treatments, 7th day) were comparable to or lower than lead
      concentrations measured in leaves of C. nodosa and other seagrass species from
      various geographical areas, probably implying that lead may play a important role
      in the worldwide decline of seagrass meadows. These lowest tissue concentrations
      were exceeded up to the 3rd day of incubation at higher exposure concentrations,
      but microtubule depolymerization at 0.5mg/L and cell death at 0.5-20mg/L were
      first detected at later time. The time period required for the onset of
      microtubule depolymerization tended to decrease as lead uptake velocity
      increased; in particular, a significant negative correlation was found between
      these variables. These results suggest that the onset of toxicity appears to be
      related to lead uptake rate rather than to the total tissue lead concentration.
      Thereby, tissue residues should be interpreted in relation to the time frame of
      the exposure, while the estimation of metal uptake rate could be utilized for
      predicting toxic effects. The data presented provide insight on metal uptake
      kinetics, toxicological effects and their linkage in seagrasses, contribute to a
      better understanding of metal toxicity on aquatic organisms and could be utilized
      in biomonitoring programmes for the identification of ecotoxicologically
      significant metal accumulation in coastal environments. 

PMID- 24681447
TI  - Metal concentrations in various fish organs of different fish species from Poyang
      Lake, China.
AB  - Concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the muscle of eleven fish
      species (bighead carp, bream, catfish, carp, crucian, Culter alburnus, grass
      carp, mandarin fish, white semiknife carp, silver carp, and yellow catfish) from
      Poyang Lake were analysed using inductive coupling plasma mass spectrometry.
      Metal levels in other organs (e.g., bladder, gill, kidney, liver, and spleen) of
      bighead carp, carp, grass carp, and silver carp were also determined. The results
      showed that metal concentrations in the muscle of all fish species were
      significantly lower than the proposed limits. Heavy metal concentrations were
      found to be substantially higher in benthic fish than in pelagic fish. Higher Hg
      contents were observed in predatory fish. In addition, various metals showed
      different affinity to fish organs. Hg was the most abundant in muscle, while Ni
      and Pb concentrations were highest in gills, Cd and Zn concentrations were
      highest in kidneys, and Cu was most commonly found in livers. Estimations of
      health risks revealed no evidence of potential threats to consumers. 

PMID- 24681448
TI  - Uptake and accumulation of endosulfan isomers and its metabolite endosulfan
      sulfate in naturally growing plants of contaminated area.
AB  - Endosulfan isomers (alpha+beta) and its main metabolite endosulfan sulfate were
      analyzed in naturally growing vegetation of pesticide contaminated area in
      Ghaziabad, India. Seven species of dominating plants were collected at different
      locations within the contaminated area. Endosulfan residues from plant parts and
      soil were extracted and determined by a gas chromatograph equipped with 63Ni
      electron capture detector (GC-ECD). Endosulfan isomers and endosulfan sulfate
      were present in almost all soil and plant samples. The concentration of total
      endosulfan in plant and soil samples analyzed ranged from 14 to 343ng g(-1) and
      13 to 938ng g(-1) respectively. Out of seven plant species studied, Vetiveria
      zizanioides (Khus Khus) and Sphenoclea zeylamica (Chikenspike) showed the highest
      and lowest accumulation respectively, with a significant difference at p<0.01
      level. Vetiveria zizanioides and Digitaria longiflora (Crab grass) could
      accumulate considerable levels of endosulfan isomers (alpha+beta) (343 and 163ng
      g(-1) respectively) and endosulfan sulfate (21 and 2ng g(-1), respectively). The
      outcomes of the study reflect the value of test species in monitoring purposes
      and their potential for remediation of contaminated sites.

PMID- 24681450
TI  - Facebook, LinkedIn-what about 'hello'?

PMID- 24681449
TI  - Clonal and cellular dynamics in germinal centers.
AB  - Germinal centers (GCs) are the site of antibody affinity maturation, a process
      that involves complex clonal and cellular dynamics. Selection of B cells bearing
      higher-affinity immunoglobulins proceeds via a stereotyped pattern whereby B
      cells migrate cyclically between the GC's two anatomical compartments. This
      process occurs in a timeframe that is well suited to analysis by intravital
      microscopy, and much has been learned in recent years by use of these techniques.
      On a longer time scale, the diversity of B cell clones and variants within
      individual GCs is also thought to change as affinity maturation progresses;
      however, our understanding of clonal dynamics in individual GCs is limited. We
      discuss recent progress in the elucidation of clonal and cellular dynamics
      patterns. 

PMID- 24681451
TI  - Where are the visionary nursing leaders of 1965?
AB  - We need a coherent approach to entry into practice more than ever. 

PMID- 24681452
TI  - Missed care.

PMID- 24681453
TI  - Missed care.

PMID- 24681454
TI  - About staffing.

PMID- 24681455
TI  - Incontinence management.

PMID- 24681456
TI  - Bed bath.

PMID- 24681459
TI  - Emergency care in america gets a near-failing grade.

PMID- 24681460
TI  - E-cigarettes raise concerns.

PMID- 24681462
TI  - Mystery CKD in Central American workers.

PMID- 24681464
TI  - More States limit access to abortions.

PMID- 24681466
TI  - Updated guidelines on hepatitis B protection for health care personnel.
AB  - Those at risk for exposure to blood or body fluids should be vaccinated. 

PMID- 24681468
TI  - The Boston marathon bombings one year later.

PMID- 24681469
TI  - The effect of face-to-face interventions in promoting physical activity.

PMID- 24681475
TI  - Remembering the fall of Bataan, April 1942.

PMID- 24681476
TI  - Developing the review question and inclusion criteria.
AB  - OVERVIEW: This article is the second in a new series on the systematic review
      from the Joanna Briggs Institute, an international collaborative supporting
      evidence-based practice in nursing, medicine, and allied health fields. The
      purpose of the series is to show nurses how to conduct a systematic review-one
      step at a time. This article details the process of articulating a review
      question to guide the search for relevant studies and discusses how to define
      inclusion criteria for the study-selection phase of the review.

PMID- 24681481
TI  - Have you FOAMed?

PMID- 24681482
TI  - Work-arounds slow electronic health record use.
AB  - The Pennsylvania Patient Safety Reporting System is a confidential, statewide
      Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery
      facilities, and birthing centers, as well as some abortion facilities, must file
      information on medical errors.Safety Monitor is a column from Pennsylvania's
      Patient Safety Authority, the authority that informs nurses on issues that can
      affect patient safety and presents strategies they can easily integrate into
      practice. For more information on the authority, visit
      www.patientsafetyauthority.org. For the original article discussed in this column
      or for other articles on patient safety, click on "Patient Safety Advisories" and
      then "Advisory Library" in the left-hand navigation menu. 

PMID- 24681483
TI  - 'Centering' care.
AB  - As part of its Raise the Voice campaign to showcase nurses who are key players in
      transforming health care, the American Academy of Nursing has identified nurses
      they call edge runners -"practical innovators who have led the way in bringing
      new thinking and new methods to a wide range of health care challenges." This is
      the fifth in AJN's series of profiles of these nursing innovators. Read and be
      proud of what nurses can accomplish. 

PMID- 24681484
TI  - The blame game.
AB  - Judging patients for poor life choices is neither right nor professional. 

PMID- 24681486
TI  - Area difference ratio for assessing nociceptive balance during laryngoscopy and
      intubation under intravenous anaesthesia: preliminary investigation of a novel
      photoplethysmographic variable.

PMID- 24681485
TI  - Evolving models for peroxisome biogenesis.
AB  - Significant progress has been made towards our understanding of the mechanism of
      peroxisome formation, in particular concerning sorting of peroxisomal membrane
      proteins, matrix protein import and organelle multiplication. Here we evaluate
      the progress made in recent years. We focus mainly on progress made in yeasts. We
      indicate the gaps in our knowledge and discuss conflicting models. 

PMID- 24681488
TI  - [Patient management: rights and duties. Inaugural conference of Dakar Principal
      Hospital 14th Medical Days (May 30th-June 1st 2013)].

PMID- 24681487
TI  - Loss of the m-AAA protease subunit AFG3L2 causes mitochondrial transport defects
      and tau hyperphosphorylation.
AB  - The m-AAA protease subunit AFG3L2 is involved in degradation and processing of
      substrates in the inner mitochondrial membrane. Mutations in AFG3L2 are
      associated with spinocerebellar ataxia SCA28 in humans and impair axonal
      development and neuronal survival in mice. The loss of AFG3L2 causes
      fragmentation of the mitochondrial network. However, the pathogenic mechanism of
      neurodegeneration in the absence of AFG3L2 is still unclear. Here, we show that
      depletion of AFG3L2 leads to a specific defect of anterograde transport of
      mitochondria in murine cortical neurons. We observe similar transport
      deficiencies upon loss of AFG3L2 in OMA1-deficient neurons, indicating that they
      are not caused by OMA1-mediated degradation of the dynamin-like GTPase OPA1 and
      inhibition of mitochondrial fusion. Treatment of neurons with antioxidants, such
      as N-acetylcysteine or vitamin E, or decreasing tau levels in axons restored
      mitochondrial transport in AFG3L2-depleted neurons. Consistently, tau
      hyperphosphorylation and activation of ERK kinases are detected in mouse neurons
      postnatally deleted for Afg3l2. We propose that reactive oxygen species signaling
      leads to cytoskeletal modifications that impair mitochondrial transport in
      neurons lacking AFG3L2.

PMID- 24681490
TI  - Phytotoxic activity and chemical composition of aqueous volatile fractions from
      Eucalyptus species.
AB  - The essential oils from four Eucalyptus species (E. spathulata, E. salubris, E.
      brockwayii and E. dundasii) have been previously confirmed to have stronger
      inhibitory effects on germination and seedling growth of silverleaf nightshade
      (Solanum elaeagnifolium Cav.). The aqueous volatile fractions (AVFs) were the
      water soluble volatile fractions produced together with the essential oils (water
      insoluble fractions) during the steam distillation process. The aim of this study
      was to further assess the phytotoxicity of AVFs from the four Eucalyptus species
      and their chemical composition. The fresh leaves of the four Eucalyptus species
      were used for the extraction of AVFs. The AVFs were tested for their phytotoxic
      effects on the perennial weed, silverleaf nightshade under laboratory conditions.
      The chemical compositions of the AVFs were determined by gas chromatograph-mass
      spectrometry (GC-MS). Our results showed that the AVFs had strong inhibition on
      the germination and seedling growth of silverleaf nightshade. The inhibition
      index increased with the increasing concentrations of AVFs. The inhibitory
      effects of the AVFs varied between different Eucalyptus species. The AVF from E.
      salubris demonstrated the highest inhibitory activity on the weed tested, with
      complete inhibition on germination and seedling growth at a concentration of 75%.
      The GC-MS analysis revealed that 1,8-cineole, isopentyl isovalerate, isomenthol,
      pinocarvone, trans-pinocarveol, alpha-terpineol and globulol were the main
      compounds in the AVFs. These results indicated that all AVFs tested had
      differential inhibition on the germination and seedling growth of silverleaf
      nightshade, which could be due to the joint effects of compounds present in the
      AVFs as these compounds were present in different quantities and ratio between
      Eucalyptus species. 

PMID- 24681489
TI  - Effect of silica particle size on macrophage inflammatory responses.
AB  - Amorphous silica particles, such as nanoparticles (<100 nm diameter particles),
      are used in a wide variety of products, including pharmaceuticals, paints,
      cosmetics, and food. Nevertheless, the immunotoxicity of these particles and the
      relationship between silica particle size and pro-inflammatory activity are not
      fully understood. In this study, we addressed the relationship between the size
      of amorphous silica (particle dose, diameter, number, and surface area) and the
      inflammatory activity (macrophage phagocytosis, inflammasome activation, IL-1beta
      secretion, cell death and lung inflammation). Irrespective of diameter size,
      silica particles were efficiently internalized by mouse bone marrow-derived
      macrophages via an actin cytoskeleton-dependent pathway, and induced caspase-1,
      but not caspase-11, activation. Of note, 30 nm-1000 nm diameter silica particles
      induced lysosomal destabilization, cell death, and IL-1beta secretion at markedly
      higher levels than did 3000 nm-10000 nm silica particles. Consistent with in
      vitro results, intra-tracheal administration of 30 nm silica particles into mice
      caused more severe lung inflammation than that of 3000 nm silica particles, as
      assessed by measurement of pro-inflammatory cytokines and neutrophil infiltration
      in bronchoalveolar lavage fluid of mice, and by the micro-computed tomography
      analysis. Taken together, these results suggest that silica particle size impacts
      immune responses, with submicron amorphous silica particles inducing higher
      inflammatory responses than silica particles over 1000 nm in size, which is
      ascribed not only to their ability to induce caspase-1 activation but also to
      their cytotoxicity. 

PMID- 24681491
TI  - Scoliosis secondary to ganglioneuroma: a case report and up to date literature
      review.
AB  - Idiopathic scoliosis is the most common form of spinal deformity in children.
      However, secondary causes of scoliosis, such as ganglioneuroma, should be always
      considered to avoid wrong diagnosis, and further investigations are required when
      there are atypical signs. We report a case of ganglioneuroma misdiagnosed as
      idiopathic scoliosis and review the literature to identify the red flags useful
      for physicians during the evaluation of a child with scoliosis. On the basis of
      both clinical and radiographic criteria that emerged from this study, we propose
      an algorithm that could help in the differential diagnosis, suggesting when to
      perform an MRI.

PMID- 24681492
TI  - Superior mesenteric artery syndrome following surgery for adolescent idiopathic
      scoliosis: a case series, review of the literature, and an algorithm for
      management.
AB  - Superior mesenteric artery (SMA) syndrome is a rare but potentially fatal
      complication following spinal fusion for scoliosis. The aims of our study were to
      identify clinical features and evaluate their importance in SMA syndrome
      following posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS)
      patients and to recommend a simple approach for the recognition and management of
      SMA syndrome. This is an IRB-approved study. Three patients in our series and 11
      patients from other published case reports who underwent PSF for adolescent
      idiopathic scoliosis were included in our study. Patient demographics, clinical
      presentation, investigations, and management were recorded and analyzed. In this
      combined series of 14 patients (mean age 14.8 years), the main presenting
      clinical features included vomiting of any kind (92.9%), abdominal
      pain/tenderness (57.1%), abdominal distension (42.9%), bilious vomiting (35.7%),
      and hypoactive bowel sounds (28.6%). Most patients presented within 2 weeks of
      surgery (71.4%). In total, 50% of patients presented with both vomiting (of any
      kind) and abdominal tenderness. The number of presenting symptoms appeared to be
      directly related to the severity of SMA syndrome. Our second patient had
      intermittent vomiting on postoperative day (POD) 3, which was initially
      considered as insignificant; she was discharged on POD 9 and readmitted for
      recurrent vomiting, during which SMA syndrome was diagnosed. Our first patient
      presented in the classical manner. Our third patient had bilious vomiting after
      discharge that started on POD 13 and increased in frequency until readmission on
      POD 27. Vomiting and abdominal pain are nonspecific symptoms following PSF;
      differentiating between SMA syndrome and postoperative ileus can be challenging.
      The highest index of suspicion applies to patients who present within the first
      week with symptoms of vomiting and abdominal pain. We propose an algorithm for
      the management of SMA syndrome, which includes a focused clinical assessment to
      evaluate for intestinal obstruction, followed by an abdominal radiography and
      barium contrast study if clinical assessment is positive. An early referral to
      general surgery should be considered especially for high-risk patients (BMI<5%
      percentile, sagittal kyphosis). Early diagnosis of SMA syndrome allows for early
      intervention, reducing the likelihood of future complications and need for
      surgery.

PMID- 24681493
TI  - [Bone and Stem Cells. Cellular network in bone micro-environment - histological
      and ultrastructural aspects -].
AB  - Bone micro-environment appears to reflect bone turnover, i.e., frequency of bone
      remodeling. There are many bone-synthesizing mature osteoblasts, bone-resorbing
      osteoclasts, and a thick cell layer of preosteoblasts overlying mature
      osteoblasts in the region which shows active bone remodeling. Bone lining cells, 
      flattened, resting form of osteoblasts cover the quiescent bone surface, in
      which, however, osteocyte-lacunar canalicular system tend to be geometrically
      well-arranged. Thus, bone micro-environment seems to be regulated by
      preosteoblasts, bone marrow stromal cells and vascular endothelial cells, as well
      as osteoblasts and osteoclasts. But, precious biological function of
      preosteoblasts and bone marrow stromal cells are still under the investigation,
      e.g., due to many phenotypes of preosteoblasts. In this review, we will introduce
      histological and ultrastructural aspects on cellular involvement in bone micro
      environment. 

PMID- 24681494
TI  - [Bone and Stem Cells. Molecular mechanisms of the differentiation and activation
      of osteoclasts derived from hematopoietic cells].
AB  - Mononuclear myeloid lineage cells, which are attracted to bone surfaces by
      chemokines and other factors, differentiate into multinucleated bone resorbing
      osteoclasts by cell fusion. Receptor activator of nuclear factor-kappaB ligand
      (RANKL) , which is expressed in mesenchymal cells, including osteocytes and
      hypertrophic chondrocytes, is essential for osteoclast differentiation and
      function. Osteoclasts have the capacity to resorb bone and impaired osteoclast
      differentiation and/or function leads to osteopetrosis, a rare disease in which
      mineralized bone cannot be removed. In contrast, excessive osteoclastogenesis
      causes diseases such as osteoporosis. Recent findings suggest that osteoclasts
      can also function as positive and negative regulators of osteoblastic bone
      formation. Thus, understanding of the molecular mechanisms that regulate
      osteoclastogenesis is important to develop therapeutic approaches to prevent bone
      diseases. This paper reviews recent findings of the molecular mechanisms
      regulating osteoclast differentiation and function. 

PMID- 24681495
TI  - [Bone and Stem Cells. The mechanism of osteogenic differentiation from
      mesenchymal stem cell].
AB  - Osteoblasts and osteocytes originate from pluripotent mesenchymal stem cells.
      Mesenchymal stem cells commit to osteogenic lineage and differentiate into mature
      osteoblasts and osteocytes through osteoprogenitor cells and preosteoblasts in
      response to multiple stimuli. The osteoblast commitment, differentiation, and
      functions are governed by several transcription factors. Among these
      transcription factors, runt-related transcription factor 2 (Runx2) is a crucial
      factor in osteoblast differentiation and controls bone formation. Differentiation
      toward these osteogenic lineage is controlled by a multitude of cytokines
      including WNTs, bone morphogenetic protein (BMP) , transforming growth factor
      beta (TGF-beta) , hedgehog, parathyroid hormone (PTH) /parathyroid hormone
      related protein (PTHrP) , insulin-like growth factor-1 (IGF-1) , fibroblast
      growth factor (FGF) , and Notch. Although regulation of Runx2 activity is a point
      of convergence of many of the signal transduction routes, there is also a high
      degree of cross-talk between these pathways. Thus, the combined action of the
      signal transduction pathways induced by some cytokines determines the commitment
      and differentiation of mesenchymal stem cells toward the osteogenic lineage. 

PMID- 24681496
TI  - [Bone and Stem Cells. Regulation of chondrocyte differentiation from mesenchymal
      stem cells].
AB  - Chondrocytes are derived from mesenchymal stem cells and play an essential role
      in endochondral ossification. Transcription factors, Sox9, Runx2, Runx3 and
      Osterix are critical for endochondral ossification, and regulate differentiation
      of mesenchymal stem cells into chondrocytes, and proliferation, maturation and
      apoptosis of chondrocytes. Recent advances in gene cloning approaches utilizing
      microarray and high-throughput sequencing technologies have revealed functional
      regulatory mechanisms of these transcription factors and contributed to
      understanding of molecular mechanisms of complex and harmonious chondrocyte
      differentiation. 

PMID- 24681498
TI  - [Bone and Stem Cells. Regulation of haematopoietic stem cell maintenance and
      mobilization by osteoclasts].
AB  - Haematopoietic stem cells (HSCs) are maintained in a specialized microenvironment
      termed "niche" in bone marrow (BM) cavities. Osteoclasts are required for
      formation of BM cavities, and thus, osteoclast-less animals exhibit BM cavity
      less osteopetrotic phenotypes. Osteoclasts were also reportedly required for
      mobilization of haematopoietic stem and progenitor cells (HSPCs) to the periphery
      from BM cavities, however, how HSCs are maintained and HSPC mobilization is
      regulated in osteoclast-less animals were largely unknown. In this review, roles
      of osteoclasts in HSC maintenance and HSPC mobilization are discussed. 

PMID- 24681497
TI  - [Bone and Stem Cells. Bone marrow microenvironment niches for hematopoietic stem
      and progenitor cells].
AB  - In bone marrow, the special microenvironments known as niches control
      proliferation and differentiation of hematopoietic stem and progenitor cells
      (HSPCs) . However, the identity and functions of the niches has been a subject of
      longstanding debate. Although it has been reported previously that osteoblasts
      lining the bone surface act as HSC niches, their precise role in HSC maintenance
      remains unclear. On the other hand, the adipo-osteogenic progenitors with long
      processes, termed CXCL12-abundant reticular (CAR) cells, which preferentially
      express the chemokine CXCL12, stem cell factor (SCF) , leptin receptor and PDGF
      receptor-beta were identified in the bone marrow. Recent studies revealed that
      endothelial cells of bone marrow vascular sinuses and CAR cells provided niches
      for HSCs. The identity and functions of various other candidate HSC niche cells,
      including nestin-expressing cells and Schwann cells would also be discussed in
      this review. 

PMID- 24681499
TI  - [Bone and Stem Cells. Immune cell regulation by the bone marrow niche].
AB  - Adult hematopoietic stem cells (HSCs) are maintained in the bone marrow and give
      rise to all blood cell types. The maintenance and the differentiation of blood
      cells including immune cells are essential for host defense and oxygen delivery.
      HSCs are maintained in microenvironments called stem cell niches, which consists
      of various cell types in bone marrow. Recently, new visualization technologies
      and assay systems brought advances in studies on the stem cell niche. In
      addition, several reports demonstrated that osteoblasts and osteocytes regulate
      not only HSC homeostasis but also immune cell differentiation, suggesting a close
      relationship between bone cells and HSCs. 

PMID- 24681500
TI  - [Bone and Stem Cells. Intravital imaging of bone marrow microenvironment].
AB  - Various kinds of cell types, such as osteoclasts, osteoblasts, hematopoietic
      cells, and mesenchymal cells, have been reported to exist in the bone marrow and
      communicate with each other. Although there have been many previous studies about
      bone marrow microenvironment, most of them were analyzed by conventional methods
      such as histological analysis and flow cytometry. These methods could not observe
      the dynamic cell movement in living bone marrow. Recently rapid development of
      fluorescent imaging techniques enables us to understand the cellular dynamics in
      vivo . That's why we have originally established an advanced imaging system for
      visualizing living bone tissues with intravital two-photon microscopy. Here we
      show the latest data and the detailed methodology of intravital imaging of bone
      marrow microenvironment, and also discuss its further application. 

PMID- 24681502
TI  - [Bone and Stem Cells. Regulatory mechanism of mesenchymal stem cell
      differentiation to osteoblasts].
AB  - Differentiation of mesenchymal stem cells to osteoblastic lineage cells is
      regulated positively by factors such as mechanical strain and parathyroid
      hormone, and is negatively regulated by factors including aging and
      glucocorticoids. Wnt/beta-catenin pathway plays an important role in controlling
      the bifurcation of mesenchymal stem cell differentiation between osteoblastic and
      adipocytic lineages. In this review, we overview the outline of the mechanism of
      action as well as interrelation of the actions of these factors in controlling
      osteoblast differentiation, with special reference to the role of interleukin-11
      in these processes. 

PMID- 24681501
TI  - [Bone and Stem Cells. Regulation of hematopoietic microenvironment by bone
      metabolism].
AB  - The skeletal and the hematopoietic systems are two different research lines being
      united through the definition of a new function of bone-forming-osteoblasts, as a
      regulatory niche for hematopoietic stem cells (HSCs) . Many molecular pathways
      reveal the interaction between the HSC and osteoblast contributory to the
      maintenance of HSC number and function. Factors that regulate osteoblastic niche
      from surrounding tissues are also known, such as sympathetic nervous system,
      macrophages, and osteocytes. Furthermore, recent study has revealed that the
      skeletal system regulates remote hematopoietic organ as well. The bone acts as a
      central regulator of multiple organs. 

PMID- 24681503
TI  - [Bone and Stem Cells. Mesenchymal stem cells and bone regeneration].
AB  - Mesenchymal stem cells (MSCs) have multi-differentiation potency, and enhance
      wound healing in various kinds of disease. Recently MSC not only differentiate
      into tissue-forming cells, but also secrete various kinds of cytokines and
      chemokines that are anti-apoptotic, immunomodulatory, angiogenic, and the cell
      mobilizing to influence extracellular environment. In addition, we show that MSC
      has a novel intercellular communication mechanism. It hopes to suggest ways to
      make safer and reliable usage of MSC in bone regeneration. 

PMID- 24681504
TI  - [Bone and Stem Cells. Isolation and immunomodulation of mesenchymal stem cells].
AB  - Mesenchymal stem cells (MSCs) are important clinical applications in treating
      immune disorders due to their multipotency, immunosuppressive properties by
      production of cytokines. However, the majority of studies rely on an in vitro
      cell expansion phase, and the properties of MSCs in vivo are still unknown,
      because there is no specific marker for MSCs. The purpose of this review is to
      provide an update on our knowledge of MSCs isolation and their immunosuppressive
      properties, focusing on bone marrow-derived MSCs. 

PMID- 24681505
TI  - [Bone and Stem Cells. Advancement of regenerative medicine in the locomotive
      system using iPS cells].
AB  - The application of iPS cells for diseases in the locomotive system includes the
      cell therapy using bone or cartilage cells and the understanding of pathogenesis
      and drug discovery for intractable diseases using patients' derived iPS cells. To
      promote these researches, the proper knowledge concerning the process from iPS
      cells to multipotential mesenchymal stromal cell (MSC) and terminally
      differentiated cells is inevitable. In addition, because there are several
      different ways to induce terminally differentiation, the biological quality of
      cells induced by each method should be compared in future. 

PMID- 24681506
TI  - [Bone and Stem Cells. The next frontier in allogeneic hematopoietic stem cell
      transplantation].
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially
      curative therapy for a majority of hematologic malignancies. However, this
      treatment procedure can still be associated with significant treatment-related
      mortality and morbidity, including regimen-related toxicity, graft-versus-host
      disease, and opportunistic infections. Recently, the advent of molecularly
      targeted therapy, such as tyrosine kinase inhibitors or antibody drugs, have
      changed the indications and techniques employed for allogeneic HSCT. In addition,
      as molecular pathogenesis of a variety of hematologic malignancies has become
      clear, it has been suggested that mutational profiling can potentially be used
      for risk stratification and to inform therapeutic decisions regarding patients
      with hematologic malignancies. Here, we review the knowledge regarding the
      current status and future directions for allogeneic HSCT in these backgrounds. 

PMID- 24681507
TI  - Recent progress in the chemical synthesis of proteins.
AB  - A methodology for chemical protein synthesis by ligation chemistry has become
      increasingly practical and applied to the synthesis of various proteins and
      glycoproteins for their structural and functional analyses. This is largely due
      to the advances in the synthesis of peptide thioester as well as to the progress
      in the extension of the ligation chemistry to a non-cysteine site, which are
      briefly summarized in this review. 

PMID- 24681508
TI  - Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype.
AB  - We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes
      in a mouse model of the human disease hereditary tyrosinemia. Delivery of
      components of the CRISPR-Cas9 system by hydrodynamic injection resulted in
      initial expression of the wild-type Fah protein in ~1/250 liver cells. Expansion
      of Fah-positive hepatocytes rescued the body weight loss phenotype. Our study
      indicates that CRISPR-Cas9-mediated genome editing is possible in adult animals
      and has potential for correction of human genetic diseases. 

PMID- 24681509
TI  - Environmentally induced transgenerational changes in seed longevity: maternal and
      genetic influence.
AB  - BACKGROUND AND AIMS: Seed longevity, a fundamental plant trait for ex situ
      conservation and persistence in the soil of many species, varies across
      populations and generations that experience different climates. This study
      investigates the extent to which differences in seed longevity are due to genetic
      differences and/or modified by adaptive responses to environmental changes.
      METHODS: Seeds of two wild populations of Silene vulgaris from alpine (wA) and
      lowland (wL) locations and seeds originating from their cultivation in a lowland
      common garden for two generations (cA1, cL1, cA2 and cL2) were exposed to
      controlled ageing at 45  degrees C, 60 % relative humidity and regularly sampled
      for germination and relative mRNA quantification (SvHSP17.4 and SvNRPD12). KEY
      RESULTS: The parental plant growth environment affected the longevity of seeds
      with high plasticity. Seeds of wL were significantly longer lived than those of
      wA. However, when alpine plants were grown in the common garden, longevity
      doubled for the first generation of seeds produced (cA1). Conversely, longevity
      was similar in all lowland seed lots and did not increase in the second
      generation of seeds produced from alpine plants grown in the common garden (cA2).
      Analysis of parental effects on mRNA seed provisioning indicated that the
      accumulation of gene transcripts involved in tolerance to heat stress was highest
      in wL, cL1 and cL2, followed by cA1, cA2 and wA. CONCLUSIONS: Seed longevity has
      a genetic basis, but may show strong adaptive responses, which are associated
      with differential accumulation of mRNA via parental effects. Adaptive adjustments
      of seed longevity due to transgenerational plasticity may play a fundamental role
      in the survival and persistence of the species in the face of future
      environmental challenges. The results suggest that regeneration location may have
      important implications for the conservation of alpine plants held in seed banks.

PMID- 24681510
TI  - Pyruvate carboxylase as a sensitive protein biomarker for exogenous steroid
      chemicals.
AB  - Assessing protein responses to endocrine disrupting chemicals is critical for
      understanding the mechanisms of chemical action and for the assessment of
      hazards. In this study, the response of the liver proteome of male rare minnows
      (Gobiocypris rarus) treated with 17beta-estradiol (E2) and females treated with
      17alpha-methyltestosterone (MT) were analyzed. A total of 23 and 24 proteins were
      identified with differential expression in response to E2 and MT, respectively.
      Pyruvate carboxylase (PC) was the only common differentially expressed protein in
      both males and females after E2- and MT-treatments. The mRNA as well as the
      protein levels of PC were significantly down-regulated compared with that of the
      controls (p < 0.05). Our results suggest that endocrine disruptors interfere with
      genes and proteins of the TCA cycle and PC may be a sensitive biomarker of
      exposure to exogenous steroid chemicals in the liver of fish. 

PMID- 24681511
TI  - Effects of the geophagous earthworm Metaphire guillelmi on sorption,
      mineralization, and bound-residue formation of 4-nonylphenol in an agricultural
      soil.
AB  - Effects of earthworms on fate of nonylphenol (NP) are obscure. Using (14)C-4
      NP111 as a representative, we studied the fate of 4-NP in an agricultural soil
      with or without the earthworm Metaphire guillelmi and in fresh cast of the
      earthworm. Sorption of 4-NP on the cast (Kd 1564) was significantly higher than
      on the parent soil (Kd 1474). Mineralization of 4-NP was significantly lower in
      the cast (13.2%) and the soil with earthworms (10.4%) than in the earthworm-free
      soil (16.0%). One nitro metabolite of 4-NP111 (2-nitro-4-NP111) was identified in
      the soil and cast, and the presence of the earthworm significantly decreased its
      amounts. The presence of earthworm also significantly decreased formation of
      bound residues of 4-NP in the soil. Our results demonstrate that earthworms could
      significantly change the fate of 4-NP, underlining that earthworm effects should
      be considered when evaluating behavior and risk of 4-NP in soil. 

PMID- 24681512
TI  - IL-1Ra selectively protects intestinal crypt epithelial cells, but not tumor
      cells, from chemotoxicity via p53-mediated upregulation of p21(WAF1) and
      p27(KIP1.).
AB  - Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side
      effect, resulting from the nonspecific cytoablative actions of chemoagents,
      including 5-fluorouracil (5-FU) and irinotecan (CPT-11). Preventive strategies
      are urgently needed for the predictable CIM. Previously, we have demonstrated an
      important role of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra)
      in the prevention of cyclophosphamide-induced mucositis in mice. In this study,
      the preventive role of rhIL-1Ra was further evaluated in 5-FU- and CPT-11-induced
      mucositis mouse models. rhIL-1Ra pretreatment reduced the incidence, severity,
      and duration of chemotherapy-induced diarrhea, through attenuating crypt
      apoptosis and improving crypt survival in wild-type mice, but not in IL-1RI(-/-),
      p53(-/-), and p21(-/-) mice. Further studies demonstrated that rhIL-1Ra promoted
      the cell cycle arrest of intestinal crypt epithelia (ICE) through elevating the
      cellular level of p21(WAF1) and p27(KIP1), which was abolished in IL-1RI(-/-) and
      p53(-/-) mice, and in p21(WAF1) and p27(KIP1) silenced IEC-6 cells. Importantly,
      the tumor growth and sensitivity to chemotherapy were not affected by rhIL-1Ra in
      cultures of tumor cell lines and in a syngeneic tumor-transplantation mouse
      model. The present study demonstrated that rhIL-1Ra effectively and specifically
      protected ICE from chemotoxicity through reversible reduction of the basal level
      of IL-1 signaling to promote normal cell cycle arrest, but not tumor cells. Our
      findings support the clinical development of rhIL-1Ra in the prevention of CIM. 

PMID- 24681513
TI  - Role of anorectic N-acylethanolamines in intestinal physiology and satiety
      control with respect to dietary fat.
AB  - Anandamide is a well-known agonist for the cannabinoid receptors. Along with
      endogenous anandamide other non-endocannabinoid N-acylethanolamines are also
      formed, apparently in higher amounts. These include mainly oleoylethanolamide
      (OEA), palmitoyelethanolamide (PEA) and linoleoylethanolamide (LEA), and they
      have biological activity by themselves being anorectic and anti-inflammatory. It
      appears that the major effect of dietary fat on the level of these molecules is
      in the gastrointestinal system, where OEA, PEA and LEA in the enterocytes may
      function as homeostatic signals, which are decreased by prolonged consumption of
      a high-fat diet. These lipid amides appear to mediate their signaling activity
      via activation of PPARalpha in the enterocyte followed by activation of afferent
      vagal fibers leading to the brain. Through this mechanism OEA, PEA and LEA may
      both reduce the consumption of a meal as well as increase the reward value of the
      food. Thus, they may function as homeostatic intestinal signals involving hedonic
      aspects that contribute to the regulation of the amounts of dietary fat to be
      ingested. 

PMID- 24681514
TI  - ZPDC glycoprotein (24 kDa) induces apoptosis and enhances activity of NK cells in
      N-nitrosodiethylamine-injected Balb/c.
AB  - Natural killer (NK) cells have anti-tumor activity in hepatocellular carcinoma
      (HCC) using secreting granules and cytotoxic ability. Recently, we isolated
      glycoprotein from Zanthoxylum piperitum DC (ZPDC) has anti-oxidant effect and
      anti-cancer effect. The objective of this study was to determine whether ZPDC
      glycoprotein enhances activity of NK cells and induces apoptosis of liver cancer
      cells in diethylnitrosamine (DEN)-treated Balb/c mice. This study evaluated the
      secreting of perforin and granzyme B and cytotoxicity of NK cells, interleukin
      (IL)-2 and IL-12, apoptosis-related factors (bid, cytochrome c, and caspase-3) in
      liver tissue using Immunoblot and ELISA. The results demonstrated that ZPDC
      glycoprotein (20mg/kg, BW) induces secretion of perforin and granzyme B and NK
      cells activity. Also, it induces expression of apoptosis-related factors (bid,
      cytochrome c, and caspase-3) in liver tissues. Collectively, ZPDC glycoprotein
      may have potential applications to prevent hepatocarcinogenesis without
      immunosuppression. 

PMID- 24681515
TI  - Distinct molecular basis for endothelial differentiation: gene expression
      profiles of human mesenchymal stem cells versus umbilical vein endothelial cells.
AB  - The capacity for endothelial differentiation has been described in mesenchymal
      stem cells (MSC) from human bone marrow. To identify genes associated with the
      endothelial differentiation potential of this cell-type, and search for the
      optimal regulatory factors, the expression profile of MSC was compared with cDNA
      from primary human umbilical vein endothelial cells as controls, using cDNA chips
      with 4096 genes. The data were corroborated by quantitative PCR, Western
      blotting, and immunocytochemistry. Among the 3948 effective genes, ~84% (3321)
      were co-expressed in both cell-types, and 627 were differentially expressed more
      than twofold in MSC versus EC. MSC highly expressed numerous stem-cell-like
      genes. Early development genes of endothelial cells, though not up-regulated, had
      a high expression in MSC, such as EDF1, MDG1, and EDG2. In contrast, mature
      endothelial growth and signal pathway genes, like VEGF, CXCR4, and CTNNB1, were
      down-regulated in MSC. In conclusion, human MSC have a distinct molecular basis
      for endothelial differentiation. 

PMID- 24681517
TI  - Large electric field-enhanced-hardness effect in a SiO2 film.
AB  - Silicon dioxide films are extensively used in nano and micro-electromechanical
      systems. Here we studied the influence of an external electric field on the
      mechanical properties of a SiO2 film by using nanoindentation technique of atomic
      force microscopy (AFM) and friction force microscopy (FFM). A giant augmentation
      of the relative elastic modulus was observed by increasing the localized electric
      field. A slight decrease in friction coefficients was also clearly observed by
      using FFM with the increase of applied tip voltage. The reduction of the friction
      coefficients is consistent with the great enhancement of sample hardness by
      considering the indentation-induced deformation during the friction measurements.

PMID- 24681516
TI  - The antitumor potential of Interleukin-27 in prostate cancer.
AB  - Prostate cancer (PCa) is of increasing significance worldwide as a consequence of
      the population ageing. Fragile elderly patients may particularly benefit from
      noninvasive and well tolerable immunotherapeutic approaches. Preclinical studies
      have revealed that the immune-regulatory cytokine IL-27 may exert anti-tumor
      activities in a variety of tumor types without discernable toxicity. We, thus,
      investigated whether IL-27 may function as anti-tumor agent in human (h) PCa and
      analyzed the rationale for its clinical application. In vitro, IL-27 treatment
      significantly inhibited proliferation and reduced the angiogenic potential of
      hPCa cells by down-regulating the pro-angiogenesis-related genes fms-related
      tyrosine kinase (FLT)1, prostaglandin G/H synthase 1/cyclooxygenase-1 (PTGS1/COX
      1) and fibroblast growth factor receptor (FGFR)3. In addition, IL-27 up-regulated
      the anti-angiogenesis-related genes such as CXCL10 and TIMP metallopeptidase
      inhibitor 3 (TIMP3). In vivo, IL-27 reduced proliferation and vascularization in
      association with ischemic necrosis of tumors developed after PC3 or DU145 cell
      injection in athymic nude mice. In patients' prostate tissues, IL-27R was
      expressed by normal epithelia and low grade PCa and lost by high tumor grade and
      stages. Nevertheless, IL-27R was expressed by CD11c(+), CD4(+) and CD8(+)
      leukocytes infiltrating the tumor and draining lymph nodes. These data lead to
      the conclusion that i) IL-27's anti-PCa potential may be fully exploited in
      patients with well-differentiated, localized IL-27R positive PCa, since in this
      case it may act on both cancerous epithelia and the tumor microenvironment; ii)
      PCa patients bearing high grade and stage tumor that lack IL-27R may benefit,
      however, from IL-27's immune-stimulatory properties.

PMID- 24681518
TI  - Cell-permeant recombinant Nanog protein promotes pluripotency by inhibiting
      endodermal specification.
AB  - A comprehensive understanding of the functional network of transcription factors
      establishing and maintaining pluripotency is key for the development of
      biomedical applications of stem cells. Nanog plays an important role in early
      development and is essential to induce natural pluripotency in embryonic stem
      cells (ESCs). Inducible gain-of-function systems allowing a precise control over
      time and dosage of Nanog activity would be highly desirable to study its vital
      role in the establishment and maintenance of pluripotency at molecular level.
      Here we engineered a recombinant cell permeable version of Nanog by fusing it
      with the cell penetrating peptide TAT. Nanog-TAT can be readily expressed in and
      purified from E. coli and binds to a consensus Nanog DNA sequence. At cellular
      level it enhances proliferation and self-renewal of ESCs in the absence of
      leukemia inhibitory factor (LIF). Nanog-TAT together with LIF acts
      synergistically as judged by enhanced clonogenicity and activation of an Oct4
      promoter-driven GFP reporter gene. Furthermore Nanog-TAT, in the absence of LIF,
      promotes pluripotency by inhibiting endodermal specification in a Stat3
      independent manner. Our results demonstrate that Nanog protein transduction is an
      attractive tool allowing control over dose and time of addition to the cells for
      studying the molecular control of pluripotency without genetic manipulation. 

PMID- 24681519
TI  - Multiple mechanisms mediate the taurine-induced proliferation of neural
      stem/progenitor cells from the subventricular zone of the adult mouse.
AB  - Taurine was previously reported to increase the proliferation of neural precursor
      cells (NPCs) from subventricular zone of the mouse brain. The results of a study
      that aimed to understand the mechanisms of this effect are presented here.
      Because taurine was not found in NPC nuclei, direct interactions with nuclear
      elements seem unlikely. A gene expression profile analysis indicated that genes
      that are regulated by taurine have roles in i) proliferation, including the Shh
      and Wnt pathways; ii) cellular adhesion; iii) cell survival; and iv)
      mitochondrial functioning. Cell cycle analysis of propidium iodide and CFSE
      labeled cells using flow cytometry revealed an increase in the number of cells in
      the S-phase and a decrease in those in the G0/G1 phase in taurine-treated
      cultures. No changes in the length of the cell cycle were observed.
      Quantification of the viable, apoptotic, and necrotic cells in cultures using
      flow cytometry and calcein-AM, annexin-V, and propidium iodide staining showed
      reductions in the number of apoptotic and necrotic cells (18% to 11% and 13% to
      10%, respectively) and increases in the number of viable cells (61% to 69%) in
      the taurine-treated cultures. Examination of the relative mitochondrial potential
      values by flow cytometry and rhodamine123 or JC-1 staining showed a 44% increase
      in the number of cells with higher mitochondrial potential and a 38% increase in
      the mitochondrial membrane potential in taurine cultures compared with those of
      controls. Taken together, the results suggest that taurine provides more
      favorable conditions for cell proliferation by improving mitochondrial
      functioning. 

PMID- 24681521
TI  - Assessing youth policies. A system of indicators for local government.
AB  - In the current European climate of economic, financial and political crisis and
      the questioning of the welfare state, assessing public policies assume a primary
      and strategic relevance in clarifying the results and contributions of policy
      actions. In this article, we aim to present the current situation in relation to
      youth policy assessment so as to formulate a system of assessment indicators in
      the sphere of Spanish local government youth policy. A review is conducted of
      some of the principal contributions in the field of constructing indicators for
      evaluating youth policies. We have found that most of these evaluation tools
      exist on a national or state level and that there is a dearth of local or
      municipal tools. The article concludes with a concrete proposal for an assessment
      tool: the SIAPJove (Sistema d'Indicadors d'Avaluacio per a les Politiques
      Municipals de Joventut or System of Assessment Indicators for Local Government
      Youth Policies) (web page: http://siapjove.udg.edu/). It provides both
      quantitative and qualitative indicators for local youth policy managers to obtain
      assessment reports with relative ease in 12 possible areas for assessment within
      youth policy. 

PMID- 24681520
TI  - Glycosaminoglycan mimetic improves enrichment and cell functions of human
      endothelial progenitor cell colonies.
AB  - Human circulating endothelial progenitor cells isolated from peripheral blood
      generate in culture cells with features of endothelial cells named late-outgrowth
      endothelial colony-forming cells (ECFC). In adult blood, ECFC display a constant
      quantitative and qualitative decline during life span. Even after expansion, it
      is difficult to reach the cell dose required for cell therapy of vascular
      diseases, thus limiting the clinical use of these cells. Glycosaminoglycans (GAG)
      are components from the extracellular matrix (ECM) that are able to interact and
      potentiate heparin binding growth factor (HBGF) activities. According to these
      relevant biological properties of GAG, we designed a GAG mimetic having the
      capacity to increase the yield of ECFC production from blood and to improve
      functionality of their endothelial outgrowth. We demonstrate that the addition of
      [OTR(4131)] mimetic during the isolation process of ECFC from Cord Blood induces
      a 3 fold increase in the number of colonies. Moreover, addition of [OTR(4131)] to
      cell culture media improves adhesion, proliferation, migration and self-renewal
      of ECFC. We provide evidence showing that GAG mimetics may have great interest
      for cell therapy applied to vascular regeneration therapy and represent an
      alternative to exogenous growth factor treatments to optimize potential
      therapeutic properties of ECFC.

PMID- 24681522
TI  - Atypical Hemolytic-Uremic Syndrome: A Clinical Review.
AB  - Atypical hemolytic-uremic syndrome (HUS) is a rare life-threatening disorder
      characterized by microangiopathic hemolytic anemia, thrombocytopenia, and
      ischemic injury to organs, especially the kidneys. Microvascular injury and
      thrombosis are the dominant histologic findings. Complement activation through
      the alternative pathway plays a critical role in the pathogenesis of atypical
      HUS. Genetic abnormalities involving complement regulatory proteins and
      complement components form the molecular basis for complement activation.
      Endothelial cell dysfunction, probably because of the effects of complement
      activation, is an intermediate stage in the pathophysiologic cascade. Atypical
      HUS has a grave prognosis. Although mortality approaches 25% during the acute
      phase, end-stage renal disease develops in nearly half of patients within a year.
      Atypical HUS has a high recurrence rate after renal transplantation, and
      recurrent disease often leads to graft loss. Plasma therapy in the form of plasma
      exchange or infusion has remained the standard treatment for atypical HUS.
      However, many patients do not respond to plasma therapy and some require
      prolonged treatment. Approved by the Food and Drug Administration in the
      treatment of atypical HUS, eculizumab is a humanized monoclonal antibody that
      blocks cleavage of complement C5 into biologically active mediators of
      inflammation and cytolysis. Although case reports have shown the efficacy of
      eculizumab, randomized clinical trials are lacking. Therapeutic strategies
      targeting endothelial cells have demonstrated promising results in experimental
      settings. Therefore, inhibitors of angiotensin-converting enzyme, HMG-CoA
      reductase, and xanthine oxidase as well as antioxidants, such as ascorbic acid,
      may have salutary effects in patients with atypical HUS. 

PMID- 24681523
TI  - Acute wiiitis representing as thrombosis of the inferior vena cava and left
      pelvic veins.
AB  - Deep venous thrombosis as a result of venous wall injury provoked by trauma is a
      common finding. It often occurs in patients with sportive overstraining, caused
      by over fatigue of the body structures. In 2007, the entity of "acute wiiitis"
      was first described in a letter to the New England Journal of Medicine. Acute
      wiiitis sums up all affections, mainly skeletal and muscle affections, provoked
      by playing Nintendo Wii, a very common and loved video-game system. Deep venous
      thrombosis as a consequence of Nintendo Wii has not been described so far. We
      present a patient with a massive free floating thrombus of the left pelvic veins
      originating from the gluteal veins and reaching into the inferior vena cava after
      playing Nintendo Wii. 

PMID- 24681524
TI  - The distribution and extent of reflux and obstruction in patients with active
      venous ulceration.
AB  - OBJECTIVES: This study was performed to precisely define the underlying
      pathophysiology in patients with active venous ulcers. METHODS: A PubMed search
      was conducted from 1991 to 2013 to select papers reporting the anatomic and
      physiologic etiology of ulceration in CEAP Class 6 patients. Studies which did
      not decipher between active and healed ulcers, did not use clear definitions, or
      did not give detailed accounts on the distribution/extent of venous pathology
      were excluded. Using the PRISMA guidelines, 12 studies were selected for further
      analysis. RESULTS: Primary insufficiency was reportedly the most common etiology
      of ulcers. Reflux most frequently occurred in the superficial system, either
      isolated or in conjunction with perforating and/or deep systems. Combined
      superficial and deep disease was observed in a median of 11.6% of limbs (range of
      0-48%). Triple system disease was seen in a median of 31.6% of limbs (range of 22
      52%). Isolated deep reflux was infrequently reported (2.1-28.4% of limbs).
      Previous deep venous thrombosis, reported in a median of 33% of patients, is
      likely underreported as it may resolve without detectable damage. CONCLUSION:
      There is a lack of data in the literature regarding the etiology of chronic
      active venous ulcers. Insufficiency of the superficial venous system from the
      micro- to the macro-vasculature has been frequently implicated in the development
      of venous ulceration. A prospective randomized controlled study is required for
      more conclusive results.

PMID- 24681525
TI  - Nitro-oxidative species in vivo biosensing: challenges and advances with focus on
      peroxynitrite quantification.
AB  - The importance of the so-called reactive nitrogen and oxygen species (RNOS) in
      biology and food technology has been widely recognized. However when these
      species are in excess, the steady-state maintained by physiological processes is
      disturbed. At this point, the nitro oxidative metabolic stress develops and its
      action in vivo over time leads to nitro-oxidative reactions in food and in living
      organisms, but also results in chronic degenerative diseases. Analytical methods
      enabling the assessment of the total antioxidant activity of a biological sample
      or a plant extract is therefore largely sought after. The ability of biosensors
      for rapid and real-time analysis that decreases the assay time and the
      possibility of automated and multi-analyte analysis at low cost has also allowed
      the quantitative and qualitative detection of RNOS. Among these RNOS,
      peroxynitrite (ONOO(-)) is a well-known inflammatory mediator during a number of
      physiological and pathological processes. Consequently, many efforts are underway
      to detect peroxynitrite in the biomedical field. This urgent demand makes the
      development of ONOO(-) specific probes of great interest. Not only they can be
      useful for the detection of disease states, but they will also allow for a
      screening-type analysis of potential signal transduction pathways in the cells.
      This invited review will critically discuss for the first time the very latest
      advancements and the challenges in the field of peroxynitrite biosensors and
      probes for in vivo and in vitro studies. Also, the main trends will be extracted,
      in order to chart the future directions and hence create an instrumental outlook.

PMID- 24681527
TI  - Commentary: epidemiological mental health research: contribution from low- and
      middle-income countries is essential.

PMID- 24681526
TI  - Hump-shaped density-dependent regulation of mosquito oviposition site-selection
      by conspecific immature stages: theory, field test with Aedes albopictus, and a
      meta-analysis.
AB  - Oviposition site selection by gravid females is an important determinant of the
      distribution, abundance, and dynamics of dipteran hematophagous insects. The
      presence of conspecific immature stages in a potential oviposition site could, on
      the one hand, indicate the suitability of that site but on the other hand could
      indicate the potential for intraspecific competition. In this paper, we present a
      graphic model suggesting that the trade-off between these two opposing forces
      could result in a hump-shaped density-dependent relationship between oviposition
      rate and conspecific immature stage density (hereafter, the "Hump-shaped
      regulation model") with positive effects of aggregation prevailing at low
      densities and negative effect of intraspecific competition prevailing at higher
      densities. We field-tested the predictions of this model at both the egg- and the
      larval levels with Aedes albopictus and evaluated if and how these relationships
      are affected by resource enrichment. We found support for the hump-shaped
      regulation model at both the larval and the egg levels. Using oviposition cups
      containing varying numbers of conspecific larvae, we showed that the oviposition
      activity of Ae. albopictus first increases and then decreases with larvae number.
      Medium enrichment resulted in higher hatching rate, and demonstrated linear
      relations for the no-enrichment treatment where larvae density range was low and
      hump-shaped relationship for the enriched medium that had a wider larvae density
      range. Using pairs of oviposition cups, we showed that at low egg densities
      mosquitoes laid more eggs on substrates containing pre-existing eggs. However, at
      higher egg densities, mosquitoes laid more eggs on a virgin substrate. Based on
      our results and on a meta-analysis, we suggest that due to study design or
      methodological shortcomings the hump-shaped regulation model is often left
      undetected and that it is likely to be more common than currently thought. 

PMID- 24681528
TI  - Assessment of targeted and non-targeted responses in cells deficient in ATM
      function following exposure to low and high dose X-rays.
AB  - Radiation sensitivity at low and high dose exposure to X-rays was investigated by
      means of chromosomal aberration (CA) analysis in heterozygous ATM mutation
      carrier and A-T patient (biallelic ATM mutation) lymphoblastoid cell lines
      (LCLs). Targeted and non-targeted responses to acutely delivered irradiation were
      examined by applying a co-culture system that enables study of both directly
      irradiated cells and medium-mediated bystander effects in the same experimental
      setting. No indication of radiation hypersensitivity was observed at doses of
      0.01 Gy or 0.1 Gy for the ATM mutation carrier LCL. The A-T patient cells also
      did not show low-dose response. There was significant increase in unstable CA
      yields for both ATM mutation carrier and A-T LCLs at 1 and 2 Gy, the A-T cells
      displaying more distinct dose dependency. Both chromosome and chromatid type
      aberrations were induced at an increased rate in the irradiated A-T cells,
      whereas for ATM carrier cells, only unstable chromosomal aberrations were
      increased above the level observed in the wild type cell line. No bystander
      effect could be demonstrated in any of the cell lines or doses applied.
      Characteristics typical for the A-T cell line were detected, i.e., high baseline
      frequency of CA that increased with dose. In addition, dose-dependent loss of
      cell viability was observed. In conclusion, CA analysis did not demonstrate low
      dose (<=100 mGy) radiosensitivity in ATM mutation carrier cells or A-T patient
      cells. However, both cell lines showed increased radiosensitivity at high dose
      exposure. 

PMID- 24681530
TI  - An anaerobic dynamic membrane bioreactor (AnDMBR) for landfill leachate
      treatment: performance and microbial community identification.
AB  - In this study, a pilot-scale anaerobic dynamic membrane bioreactor was operated
      for 142days for treating landfill leachate. Under stable operation, average COD
      removal efficiency of 62.2% was achieved when the reactor was fed with the raw
      leachate containing total ammonium concentration above 3000mg/L and COD above
      13,000mg/L. The methane content in the biogas was in the range of 70-90%, and the
      average methane yield was 0.34L/g CODremoved at the organic loading rate of
      4.87kg COD/(m(3)d). Pyrosequencing analyses indicated that during the operation
      the archaeal community was relatively stable while obvious changes took place in
      the bacterial community. Alkaliphilus, Petrimonas, Fastidiosipila and vadinBC27
      were the abundant fermentation bacteria in bacterial communities. Moreover,
      phylum TM6 gradually became the most dominant bacterial community and reached the
      highest relative abundance of 32.9% as the operation elapsed. In archaeal
      communities, genus Methanosarcina was identified as the dominant methanogen. 

PMID- 24681529
TI  - Tissue engineering bone using autologous progenitor cells in the peritoneum.
AB  - Despite intensive research efforts, there remains a need for novel methods to
      improve the ossification of scaffolds for bone tissue engineering. Based on a
      common phenomenon and known pathological conditions of peritoneal membrane
      ossification following peritoneal dialysis, we have explored the possibility of
      regenerating ossified tissue in the peritoneum. Interestingly, in addition to
      inflammatory cells, we discovered a large number of multipotent mesenchymal stem
      cells (MSCs) in the peritoneal lavage fluid from mice with peritoneal catheter
      implants. The osteogenic potential of these peritoneal progenitor cells was
      demonstrated by their ability to easily infiltrate decalcified bone implants,
      produce osteocalcin and form mineralized bone in 8 weeks. Additionally, when
      poly(l-lactic acid) scaffolds loaded with bone morphogenetic protein-2 (a known
      osteogenic differentiation agent) were implanted into the peritoneum, signs of
      osteogenesis were seen within 8 weeks of implantation. The results of this
      investigation support the concept that scaffolds containing BMP-2 can stimulate
      the formation of bone in the peritoneum via directed autologous stem and
      progenitor cell responses. 

PMID- 24681531
TI  - Urinary 1-methylhistidine and 3-methylhistidine, meat intake, and colorectal
      adenoma risk.
AB  - Self-reported red and processed meat intake has been positively associated with
      colorectal adenoma and cancer; however, measurement error in self-reported data
      can attenuate risk estimates, increasing the need for improved exposure
      assessment methods to better understand this association. A controlled feeding
      study revealed that urinary 1-methylhistidine and 3-methylhistidine levels were
      dose-dependently associated with meat intake; our aim was to examine these
      analytes in relation to colorectal adenoma. Individuals undergoing routine cancer
      screening by sigmoidoscopy or colonoscopy were recruited for a colorectal adenoma
      case-control study; participants completed a food frequency questionnaire and a
      meat questionnaire, and donated urine. Urinary 1-methylhistidine and 3
      methylhistidine levels were measured in 131 case-control pairs (age, sex, and
      smoking matched); odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated by logistic regression. Although the mean self-reported red meat
      intake was higher in cases (59 g/day) than in controls (48 g/day), the mean
      urinary 1-methylhistidine and 3-methylhistidine levels did not differ by case
      status (P=0.72). Neither urinary 1-methylhistidine nor urinary 3-methylhistidine
      was associated with colorectal adenoma (OR continuous=0.90, 95% CI: 0.53-1.54; OR
      continuous=0.90, 95% CI: 0.69-1.17, respectively). A variable combining self
      reported red meat intake with urinary 1-methylhistidine and 3-methylhistidine
      levels was not associated with colorectal adenoma. Analyzing urine samples from
      multiple days from 17 individuals revealed intraclass correlations of 0.52 and
      0.49 for 1-methylhistidine and 3-methylhistidine, respectively; this variability
      could result in attenuated risks. Urinary 1-methylhistidine and 3-methylhistidine
      levels, measured in one sample, were not associated with colorectal adenoma.

PMID- 24681532
TI  - Awareness of colonoscopy as a screening method for colorectal cancer and its
      uptake in Spain.
AB  - The objective of this study was to describe awareness levels of colonoscopy as a
      screening procedure for colorectal cancer (CRC), to study its uptake and analyze
      possible associated factors in Spain. This was a cross-sectional study using data
      from the Oncobarometro survey, carried out by face-to-face interviews with a
      representative national sample of the Spanish population aged 18 years and older.
      Awareness was assessed using the following questions: 'Do you know of any
      examination procedures or medical technique used to detect cancer?' and 'I'm
      going to list some screening procedures (including colonoscopy) to see if you
      know of them as a cancer screening test or whether this is the first time you
      have heard of them'. To evaluate colonoscopy uptake, participants were asked
      whether they had undergone a colonoscopy in the past 2 years. The independent
      variables included sociodemographic, socioeconomic, and health-related factors.
      65.7% of the study population was aware of colonoscopy as a screening tool.
      Individuals from lower socioeconomic groups or those who only had primary
      education showed a lower level of awareness. 12.8% of participants had undergone
      a colonoscopy in the past 2 years. This number increased to 45% in the Spanish
      Autonomous Communities, where screening programs are in place. Colonoscopy
      screening rates are 10.28 times higher among those who had fecal occult blood
      testing during the previous 2 years. There is an inverse relationship between
      social inequality and both awareness and uptake of colonoscopy. Consequently, for
      screening to be more effective, interventions that reduce barriers to access for
      target populations should be implemented. 

PMID- 24681533
TI  - Theories of cancer origin.
AB  - Throughout centuries, many theories have been proposed to explain the origin of
      cancer. In this review, some of them are presented and briefly commented upon.
      The theories discussed are divided into epigenetic and genetic ones, with the
      latter further classified into gene-based and genome-based hypotheses. Multistage
      cancer development leading to the mutator, malignant cell phenotype is also
      described. Finally, the current hot topic of cancer stem cells is presented. 

PMID- 24681534
TI  - [About Snake bites in children at the Fez University Hospital (Morocco)].
AB  - The author stresses the importance of the specificity of immunotherapy and
      identifies the two appropriate antivenoms for North Africa and the Middle East in
      general, and Morocco in particular. Due to the very good tolerance of new
      generation antivenoms, the author recommends systematically administer antivenom
      as early as possible to avoid unfavorable clinical progression, particularly in
      children and pregnant women.. 

PMID- 24681535
TI  - Amphotericin forms an extramembranous and fungicidal sterol sponge.
AB  - For over 50 years, amphotericin has remained the powerful but highly toxic last
      line of defense in treating life-threatening fungal infections in humans with
      minimal development of microbial resistance. Understanding how this small
      molecule kills yeast is thus critical for guiding development of derivatives with
      an improved therapeutic index and other resistance-refractory antimicrobial
      agents. In the widely accepted ion channel model for its mechanism of cytocidal
      action, amphotericin forms aggregates inside lipid bilayers that permeabilize and
      kill cells. In contrast, we report that amphotericin exists primarily in the form
      of large, extramembranous aggregates that kill yeast by extracting ergosterol
      from lipid bilayers. These findings reveal that extraction of a polyfunctional
      lipid underlies the resistance-refractory antimicrobial action of amphotericin
      and suggests a roadmap for separating its cytocidal and membrane-permeabilizing
      activities. This new mechanistic understanding is also guiding development of
      what are to our knowledge the first derivatives of amphotericin that kill yeast
      but not human cells. 

PMID- 24681537
TI  - Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark.
AB  - We report the identification of a new type of histone mark, lysine 2
      hydroxyisobutyrylation (Khib), and identify the mark at 63 human and mouse
      histone Khib sites, including 27 unique lysine sites that are not known to be
      modified by lysine acetylation (Kac) and lysine crotonylation (Kcr). This histone
      mark was initially identified by MS and then validated by chemical and
      biochemical methods. Histone Khib shows distinct genomic distributions from
      histone Kac or histone Kcr during male germ cell differentiation. Using chromatin
      immunoprecipitation sequencing, gene expression analysis and immunodetection, we
      show that in male germ cells, H4K8hib is associated with active gene
      transcription in meiotic and post-meiotic cells. In addition, H4K8ac-associated
      genes are included in and constitute only a subfraction of H4K8hib-labeled genes.
      The histone Khib mark is conserved and widely distributed, has high stoichiometry
      and induces a large structural change. These findings suggest its critical role
      on the regulation of chromatin functions. 

PMID- 24681536
TI  - Golgi sorting regulates organization and activity of GPI proteins at apical
      membranes.
AB  - Here we combined classical biochemistry with new biophysical approaches to study
      the organization of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI
      APs) with high spatial and temporal resolution at the plasma membrane of
      polarized epithelial cells. We show that in polarized MDCK cells, after sorting
      in the Golgi, each GPI-AP reaches the apical surface in homoclusters. Golgi
      derived homoclusters are required for their subsequent plasma membrane
      organization into cholesterol-dependent heteroclusters. By contrast, in
      nonpolarized MDCK cells, GPI-APs are delivered to the surface as monomers in an
      unpolarized manner and are not able to form heteroclusters. We further
      demonstrate that this GPI-AP organization is regulated by the content of
      cholesterol in the Golgi apparatus and is required to maintain the functional
      state of the protein at the apical membrane. Thus, in contrast to fibroblasts, in
      polarized epithelial cells, a selective cholesterol-dependent sorting mechanism
      in the Golgi regulates both the organization and function of GPI-APs at the
      apical surface. 

PMID- 24681539
TI  - High-content screening of yeast mutant libraries by shotgun lipidomics.
AB  - To identify proteins with a functional role in lipid metabolism and homeostasis
      we designed a high-throughput platform for high-content lipidomic screening of
      yeast mutant libraries. To this end, we combined culturing and lipid extraction
      in 96-well format, automated direct infusion nanoelectrospray ionization, high
      resolution Orbitrap mass spectrometry, and a dedicated data processing framework
      to support lipid phenotyping across hundreds of Saccharomyces cerevisiae mutants.
      Our novel approach revealed that the absence of genes with unknown function
      YBR141C and YJR015W, and the transcription factor KAR4 precipitated distinct
      lipid metabolic phenotypes. These results demonstrate that the high-throughput
      shotgun lipidomics platform is a valid and complementary proxy for high-content
      screening of yeast mutant libraries. 

PMID- 24681538
TI  - PSEA: Kinase-specific prediction and analysis of human phosphorylation
      substrates.
AB  - Protein phosphorylation catalysed by kinases plays crucial regulatory roles in
      intracellular signal transduction. With the increasing number of kinase-specific
      phosphorylation sites and disease-related phosphorylation substrates that have
      been identified, the desire to explore the regulatory relationship between
      protein kinases and disease-related phosphorylation substrates is motivated. In
      this work, we analysed the kinases' characteristic of all disease-related
      phosphorylation substrates by using our developed Phosphorylation Set Enrichment
      Analysis (PSEA) method. We evaluated the efficiency of our method with
      independent test and concluded that our approach is reliable for identifying
      kinases responsible for phosphorylated substrates. In addition, we found that
      Mitogen-activated protein kinase (MAPK) and Glycogen synthase kinase (GSK)
      families are more associated with abnormal phosphorylation. It can be anticipated
      that our method might be helpful to identify the mechanism of phosphorylation and
      the relationship between kinase and phosphorylation related diseases. A user
      friendly web interface is now freely available at
      http://bioinfo.ncu.edu.cn/PKPred_Home.aspx. 

PMID- 24681541
TI  - Meta-analysis of the risk of upper gastrointestinal hemorrhage with combination
      therapy of selective serotonin reuptake inhibitors and non-steroidal anti
      inflammatory drugs.
AB  - It is thought that both selective serotonin reuptake inhibitors (SSRIs) and non
      steroidal anti-inflammatory drugs (NSAIDs) can cause the adverse reaction of
      upper gastrointestinal hemorrhage (UGIH). To evaluate differences in the
      probability of UGIH occurring when SSRIs, NSAIDs, or both combined are
      administered, the authors performed a systematic review of related articles and a
      meta-analysis of data in those articles, which were identified by searching the
      literature published between 1999 and 2012 using PubMed, Scirus, and Google
      Scholar. The odds ratios were calculated using the Mantel-Haenszel method. The
      integrated odds ratios for SSRIs only, NSAIDs only, and the combination were 1.73
      (0.65-2.82), 2.55 (1.51-3.59), and 4.02 (2.89-5.15), respectively. Use of the
      combination resulted in an odds ratio 2.32 times higher than use of either alone.
      Since the combination of SSRIs and NSAIDs resulted in a significantly higher risk
      of UGIH than either type of drug alone, clinicians should avoid use of the
      combination as much as possible. If it is necessary to administer both kinds of
      drugs, the minimum dosage should be prescribed for the shortest time period
      possible, and patients, particularly elderly patients, should be closely
      monitored for development of UGIH and other complications. 

PMID- 24681540
TI  - Antidepressant activity of astilbin: involvement of monoaminergic
      neurotransmitters and BDNF signal pathway.
AB  - Depression and related mood disorders are among the world's greatest public
      health problems. Previous studies have demonstrated that astilbin (AST) has broad
      pharmacological functions which may modulate numerous pathways, such as
      antioxidant, scavenging free radicals, anti-inflammatory and so on, similarly to
      some of other flavonoids. In this study, the antidepressant-like effect of AST
      was investigated using chronic unpredictable mild stress (CUMS) model of
      depression in mice. The results showed that chronic administration of AST at
      doses of 10, 20 and 40 mg/kg (intraperitoneally (i.p.), 21 d) reduced depressive
      like behaviors of mice in the forced swim test (FST), tail suspension test (TST)
      and sucrose preference test (SPT) without affecting locomotor activity. AST
      increased the contents of serotonin (5-HT) and dopamine (DA) in the frontal
      cortex of CUMS mice. Additionally, it was shown that AST treatment restored the
      CUMS-induced inhibition of extracellular signal-regulated kinase (ERK) 1/2 and
      AKT phosphorylation in the frontal cortex, conformed to the brain-derived
      neurotrophic factor (BDNF) expression. Our findings suggest that AST has
      antidepressant activities and the mechanisms, at least in part, relate to up
      regulation of monoaminergic neurotransmitters (5-HT and DA) and activation of the
      BDNF signaling pathway. 

PMID- 24681542
TI  - Higher melanoma incidence in coastal versus inland counties in California.
AB  - The incidence of melanoma is increasing and there is significant variation by
      geographical location between and within countries. We sought to determine the
      incidence of melanoma in coastal versus inland counties in California. Data on
      melanoma incidence were obtained for 2000-2009 from the Surveillance,
      Epidemiology, and End Results program of the National Cancer Institute.
      Incidences for melanoma in situ and invasive melanoma for major racial and ethnic
      groups for coastal and inland counties were analyzed using multivariable Poisson
      regression, with adjustment for socioeconomic factors (income, education),
      ultraviolet index, and latitude. Further analyses were carried out for the non
      Hispanic white population through stratification of in-situ versus invasive
      melanoma, age, thickness, and anatomic distribution. The incidence of melanoma in
      situ is greater in coastal counties of California than inland counties (incidence
      rate ratio 1.23, 95% confidence interval 1.04-1.47) after adjusting for
      socioeconomic factors, ultraviolet index, and latitude. In non-Hispanic whites,
      this difference is significant for in-situ and thin (<= 1.00 mm) melanomas, but
      not for melanomas of greater thickness. In melanoma in situ and thin melanomas in
      non-Hispanic whites, the incidence is greater in coastal versus inland counties.
      Causes may include differences in exposures, differences in detection, or
      artifacts such as residual confounding. Our study highlights the need for further
      research in identifying and addressing these differences.

PMID- 24681543
TI  - A liver-X-receptor ligand, T0901317, attenuates IgE production and airway
      remodeling in chronic asthma model of mice.
AB  - The liver-X-receptors have shown anti-inflammatory ability in several animal
      models of respiratory disease. Our purpose is to investigate the effect of LXR
      ligand in allergen-induced airway remodeling in mice. Ovalbumin-sensitized mice
      were chronically challenged with aerosolized ovalbumin for 8 weeks. Some mice
      were administered a LXR agonist, T0901317 (12.5, 25, 50 mg/kg bodyweight) before
      challenge. Then mice were evaluated for airway inflammation, airway
      hyperresponsiveness and airway remodeling. T0901317 failed to attenuate the
      inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid. But the
      application of T0901317 reduced the thickness of airway smooth muscle and the
      collagen deposition. Meanwhile, T0901317 treatment evidently abolished the high
      level of OVA-specific IgE, TGF-beta1 and MMP-9 in lung. So LXRs may attenuate the
      progressing of airway remodeling, providing a potential treatment of asthma. 

PMID- 24681544
TI  - New enzyme insights drive advances in commercial ethanol production.
AB  - Innovations at a small scale through enzyme discovery in the laboratory can have
      large scale impacts when rolled out in an industrial process, and this is
      evidenced in recent advances for commercial ethanol production. In the starch to
      ethanol processes, new enzyme product launches squeeze even more value from an
      already efficient process, as evidenced in new use of proteases for oil release
      and cellulases for downstream processing and ethanol yield. As for biomass to
      ethanol, diverse new thermophilic enzymes, expansins and auxiliary activity (AA)
      collections are growing rapidly. Our mechanistic understanding of the functions
      of AA family 9, cellulose binding modules, and cellulase/xylanase synergy will
      lead to continued improvements in overall enzymatic conversion, thus reducing
      cost for cellulosic ethanol (or other biofuel) production. 

PMID- 24681545
TI  - A macroprolactin level today may keep health care cost and the surgical knife at
      bay.

PMID- 24681546
TI  - Comparison of urinary tract infection rates among 2- to 12-month-old febrile
      infants with RSV infections using 1999 and 2011 AAP diagnostic criteria.
AB  - BACKGROUND: Infants with RSV infections have been found to have a clinically
      significant rate of urinary tract infections (UTIs). The American Academy of
      Pediatrics (AAP) published a revised Clinical Practice Guideline on UTIs in 2011,
      which includes major changes in diagnostic criteria for UTIs. Past research has
      been done using previous diagnostic criteria. The objective of the study is to
      assess the rate of UTIs in febrile infants with respiratory syncytial virus (RSV)
      infections according to the 2011 revised AAP Diagnostic Criteria and compare the
      rate of UTIs against the 1999 AAP Diagnostic Criteria. METHODS: A retrospective
      comparative study of febrile infants (2-12 months) with RSV infections admitted
      to the Inpatient Pediatric unit of Lincoln Medical and Mental Center, Bronx, NY,
      from September through April 2006 to 2012. We applied the AAP's 1999 and 2011
      diagnostic criteria for UTIs separately to assess the rates of UTIs. RESULTS: A
      total of 359 RSV-positive febrile patients who were investigated for UTIs were
      enrolled. Pyuria was found in 11.1% (40/359), positive urine culture 10 000 to 50
      000 was found in 1.4% (5/359) and >=50 000 in 4.7% (17/359). The rate of UTIs
      using AAP's 1999 criteria was 6.1% (22/359), and using the 2011 criteria the rate
      was 1.1% (4/359). The rate of UTIs was significantly different between the 2
      groups (odds ratio [confidence interval] = 0.17 [0.05, 0.5], P = .001).
      CONCLUSIONS: The rate of UTIs in RSV-positive febrile infants is very low (1.1%)
      with the 2011 AAP diagnostic criteria. Previously described increased risk of
      UTIs may represent asymptomatic bacteriuria or contaminated specimens.

PMID- 24681548
TI  - Use of gold nanoparticles as crosslink agent to form chitosan nanocapsules: study
      of the direct interaction in aqueous solutions.
AB  - A systematic study of the interaction between free anionic gold nanoparticles and
      chitosan in a solution is presented. A spectroscopic study of the interaction
      between 10nm gold nanoparticles and low molecular weight chitosan is reported as
      a function of the concentration and pH of the polymer in a solution. Zeta
      potential measurements and TEM images indicate the effective aggregation of the
      nanoparticles in the presence of chitosan. At the same time, anionic gold
      nanoparticles act as crosslink agents to form chitosan nanocapsules with an
      average molecular size of 260nm. The changes of the surface plasmon band due to
      the adsorption of the polymer on the nanoparticle surface allow using of the
      citrate gold nanoparticles as sensors of the polymer for analytical purposes. The
      limit of detection for chitosan biopolymer is 69nM. The optimum pH for the
      interaction between the biopolymer and the nanoparticles is found at a value of
      6.4, obtained from spectrophotometric measurements and applying a deconvolution
      analysis of the experimental data. A simple model based on molecular surface
      electrostatic interactions is proposed to understand the pH dependence of the
      investigated system. 

PMID- 24681547
TI  - Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common
      target, common therapies.
AB  - Cadherin-11 (CDH11), associated with epithelial to mesenchymal transformation in
      development, poor prognosis malignancies and cancer stem cells, is also a major
      therapeutic target in rheumatoid arthritis (RA). CDH11 expressing basal-like
      breast carcinomas and other CDH11 expressing malignancies exhibit poor prognosis.
      We show that CDH11 is increased early in breast cancer and ductal carcinoma in
      situ. CDH11 knockdown and antibodies effective in RA slowed the growth of basal
      like breast tumors and decreased proliferation and colony formation of breast,
      glioblastoma and prostate cancer cells. The repurposed arthritis drug celecoxib,
      which binds to CDH11, and other small molecules designed to bind CDH11 without
      inhibiting COX-2 preferentially affect the growth of CDH11 positive cancer cells
      in vitro and in animals. These data suggest that CDH11 is important for malignant
      progression, and is a therapeutic target in arthritis and cancer with the
      potential for rapid clinical translation. 

PMID- 24681549
TI  - Promising antioxidant and anticancer (human breast cancer) oxidovanadium(IV)
      complex of chlorogenic acid. Synthesis, characterization and spectroscopic
      examination on the transport mechanism with bovine serum albumin.
AB  - A new chlorogenate oxidovanadium complex (Na[VO(chlorog)(H2O)3].4H2O) was
      synthesized by using Schlenk methodology in the course of a reaction at inert
      atmosphere in which deprotonated chlorogenic acid ligand binds to
      oxidovanadium(IV) in a reaction experiment controlled via EPR technique and based
      in a species distribution diagram. The compound was characterized by FTIR, EPR,
      UV-visible and diffuse reflectance spectroscopies and thermogravimetric,
      differential thermal and elemental analyses. The ligand and the complex were
      tested for their antioxidant effects on DPPH (1,1-diphenyl-2-picrylhydrazyl
      radical), ABTS(+) (radical cation of 2,2'-azinobis(3-ethylbenzothiazoline-6
      sulfonic acid) diammonium salt), O2(-), OH and ROO radicals and their cytotoxic
      activity on different cancer cell lines (SKBR3, T47D and MDAMB231) and primary
      human mammary epithelial cells. The complex behaved as good antioxidant agent
      with strongest inhibitory effects on O2(-), OH and ROO radicals and exhibited
      selective cytotoxicity against SKBR3 cancer cell line. Albumin interaction
      experiments denoted high affinity toward the complex and its calculated binding
      constant was indicative of a strong binding to the protein. Based on this study,
      it is hypothesized that Na[VO(chlorog)(H2O)3].4H2O would be a promising candidate
      for further evaluation as an antioxidant and anticancer agent. 

PMID- 24681551
TI  - Oxidative stress, cell cycle arrest and differentiation contribute toward the
      antiproliferative action of BSO and calcitriol on Caco-2 cells.
AB  - The prognosis and incidence of colon cancer are linked to vitamin D3 serum
      levels. To evaluate the effects of D,L-buthionine-S,R-sulfoximine (BSO),
      1,25(OH)2D3 and their combination on intestinal Caco-2 cell growth, to elucidate
      the possible cellular mechanisms involved in their antiproliferative action, and
      to determine whether BSO acts as a sensitizer to 1,25(OH)2D3 treatment, enabling
      minimization of the toxic effects caused by high doses of the steroid. Human
      colon cancer Caco-2 cells were treated with 1,25(OH)2D3, BSO, both, or vehicle.
      Cell proliferation was evaluated by crystal violet staining. Cell cycle and
      mitochondrial membrane potential were measured by flow cytometry. Total
      glutathione, catalase, superoxide dismutase, superoxide anion levels, and
      alkaline phosphatase activities were analyzed by spectrophotometry. DNA
      fragmentation was evaluated using the terminal dUTP nick end labeling assay. BSO
      and 1,25(OH)2D3 inhibited Caco-2 cell growth, an effect that was higher with the
      combined treatment. The antiproliferative effect produced by the combination
      could be protected by ascorbic acid. BSO plus 1,25(OH)2D3 induced cell cycle
      arrest and suppressed cell division. Total glutathione decreased and superoxide
      anion increased with BSO and BSO plus 1,25(OH)2D3. Catalase activity increased
      with the combined treatment. Mitochondrial membrane potential and alkaline
      phosphatase activity were altered by 1,25(OH)2D3 alone or plus BSO. The
      percentage of terminal dUTP nick end labeling-positive cells was increased. BSO
      increases the antiproliferative effect of 1,25(OH)2D3 on Caco-2 cells through
      induction of oxidative stress, which occurs simultaneously with DNA breakage. The
      antioxidant system can partially compensate the damage induced by BSO plus
      1,25(OH)2D3. Cell differentiation induction is also involved in the response to
      the combined treatment. 

PMID- 24681550
TI  - Scleral cross section area and volume and axial length.
AB  - PURPOSE: To examine whether the scleral cross sectional area and estimated
      scleral volume are associated with a longer axial length in human eyes. METHODS:
      Histologic anterior-posterior sections running through the pupil and the optic
      nerve head were examined. Using a light microscope, we measured the thickness of
      the sclera at the limbus, ora serrata, equator, midpoint between equator and
      posterior pole (MPEPP), peripapillary region and posterior pole. Additionally we
      determined the length and the cross section area of the sclera. RESULTS: The
      histomorphometric study included 214 human globes of 214 subjects (mean age:
      62.5+/-13.9 years) (147 eyes enucleated due to malignant choroidal melanoma or
      due to other non-glaucomatous reasons; 67 eyes enucleated due to secondary angle
      closure glaucoma). Mean axial length was 25.1+/-1.8 mm (median: 24.0 mm; range:
      20-35 mm). Scleral thickness measurements decreased with increasing axial length
      for values taken at the equator (P = 0.008; correlation coefficient r = -0.18),
      MPEPP (P<0.001;r:-0.47), optic nerve head border (P<0.001;r = -0.47) and
      posterior pole (P<0.001;r = -0.54). Scleral cross section area decreased
      significantly with increasing axial lengths for the regions at or behind the
      equator (P = 0.002;r = -0.21), at or behind the MPEPP (P = 0.001;r = -0.25), and
      at or behind the optic nerve head border (P = 0.001;r = -0.24). Scleral volume
      measurements were not significantly associated with axial length. CONCLUSIONS:
      Despite an associated increase in surface area, eyes with longer axial length do
      not have an increase in scleral volume. It may point against a scleral volume
      enlargement to play a role in the process of axial elongation.

PMID- 24681552
TI  - Effect of maternal steroid on developing diaphragm integrity.
AB  - Antenatal steroids reduce the severity of initial respiratory distress of
      premature newborn babies but may have an adverse impact on other body organs. The
      study aimed to examine the effect of maternal steroids on postnatal respiratory
      muscle function during development and elucidate the mechanisms underlying the
      potential myopathy in newborn rats. Pregnant rats were treated with intramuscular
      injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn
      diaphragms were dissected for assessment of contractile function at 2 d, 7 d or
      21 d postnatal age (PNA), compared with age-matched controls. The expression of
      myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of
      intracellular molecular signalling were measured using quantitative PCR and/or
      Western blot. With advancing PNA, neonatal MHC gene expression decreased
      progressively while MHC IIb and IIx isoforms increased. Protein metabolic
      signalling showed high baseline activity at 2 d PNA, and significantly declined
      at 7 d and 21 d. Antenatal administration of betamethasone significantly
      decreased diaphragm force production, fatigue resistance, total fast fibre
      content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm.
      These responses were not observed in 2 d or 7 d postnatal diaphragm. Results
      demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic
      dysfunction at 21 d PNA, which is attributed to MHC II protein loss and
      impairment of the anabolic signalling pathway. Developmental modifications in MHC
      fibre composition and protein signalling account for the age-specific diaphragm
      dysfunction. 

PMID- 24681553
TI  - Regression models for log-normal data: comparing different methods for
      quantifying the association between abdominal adiposity and biomarkers of
      inflammation and insulin resistance.
AB  - We compared six methods for regression on log-normal heteroscedastic data with
      respect to the estimated associations with explanatory factors (bias and standard
      error) and the estimated expected outcome (bias and confidence interval). Method
      comparisons were based on results from a simulation study, and also the
      estimation of the association between abdominal adiposity and two biomarkers; C
      Reactive Protein (CRP) (inflammation marker,) and Insulin Resistance (HOMA-IR)
      (marker of insulin resistance). Five of the methods provide unbiased estimates of
      the associations and the expected outcome; two of them provide confidence
      intervals with correct coverage. 

PMID- 24681554
TI  - Length of stay for mental and behavioural disorders postpartum in primiparous
      mothers: a cohort study.
AB  - BACKGROUND: Previous research showed that there was a significant increase in
      psychiatric hospital admission of postpartum mothers. The aim of the current
      study is to describe the length of hospital stays and patient days for mental and
      behavioural disorders (MBD) of new mothers in the first year after birth. METHOD:
      This was a cohort study based on linked population data between the New South
      Wales (NSW) Midwives Data Collection (MDC) and the NSW Admitted Patients Data
      Collection (APDC). The study population included primiparous mothers aged from 18
      to 44 who gave birth between 1 July 2000 and 31 December 2005. The Kaplan-Meier
      method was used to describe the length of hospital stay for MBD. RESULTS: For
      principal diagnoses of MBD, the entire length of hospital stay in the first year
      postpartum was 11.38 days (95% CI: 10.70-12.06) for mean and 6 days (95% CI: 5.87
      6.13) for median. The length of hospital stay per admission was 8.47 days (95%
      CI: 8.03-8.90) for mean and 5 days (95% CI: 4.90-5.10) for median. There were
      5,129 patient days of hospital stay per year for principal diagnoses of
      postpartum MBD in new mothers between 1 July 2000 and 31 December 2005 in NSW,
      Australia. CONCLUSIONS: MBD, especially unipolar depressions, adjustment
      disorders, acute psychotic episodes, and schizophrenia, or schizophrenia-like
      disorders during the first year after birth, placed a significant burden on
      hospital services due to long hospital stays and large number of admissions.

PMID- 24681556
TI  - Degradation of drugs in water with advanced oxidation processes and ozone.
AB  - The aim of this paper is to assess the degradation of a mixture of ibuprofen and
      clofibric acid and to study the mineralization and toxicity following ozone
      treatment. To this end, a comparison is presented of the experimental results
      obtained from ozone treatment using atmospheric air as the feed gas (Experiment
      I, [O3] = 15 gN/m(3)), with and without addition of H2O2, and those obtained
      under the same conditions but using concentrated oxygen as the feed gas, obtained
      by pressure swing adsorption technology (Experiment II, [O3] = 200 gN/m(3)). All
      tests were conducted using a pilot scale reactor. Under (Experiment II)
      conditions, degradation exceeded 99% and up to 60% mineralization was achieved
      for initial compound concentrations, and hydraulic retention time was reduced by
      75% compared to (Experiment I). The results of toxicity tests show through
      increasing the production of ozone gas in (Experiment II), toxicity was
      eliminated at initial study concentrations of <=1 mg/l for all treatment times
      studied. 

PMID- 24681555
TI  - Effects of sludge retention times on nutrient removal and nitrous oxide emission
      in biological nutrient removal processes.
AB  - Sludge retention time (SRT) is an important factor affecting not only the
      performance of the nutrient removal and sludge characteristics, but also the
      production of secondary pollutants such as nitrous oxide (N2O) in biological
      nutrient removal (BNR) processes. Four laboratory-scale sequencing batch reactors
      (SBRs), namely, SBR5, SBR10, SBR20 and SBR40 with the SRT of 5 d, 10 d, 20 d and
      40 d, respectively, were operated to examine effects of SRT on nutrient removal,
      activated sludge characteristics and N2O emissions. The removal of chemical
      oxygen demand or total phosphorus was similar under SRTs of 5-40 d, SRT mainly
      affected the nitrogen removal and the optimal SRT for BNR was 20 d. The molecular
      weight distribution of the effluent organic matters was in the range of 500-3,000
      Da under SRTs of 5-40 d. The lowest concentration of the effluent soluble
      microbial products concentration was obtained at the SRT of 5 d. Nitrifier growth
      was limited at a short SRT and nitrite existed in the effluent of SBR5. With
      increasing SRTs, mixed liquor suspended solids concentration increased while the
      excess sludge production was reduced due to the high endogenous decay rate at
      high SRTs. Endogenous decay coefficients were 0.020 d-1, 0.036 d-1, 0.037 d-1 and
      0.039 d-1 under SRTs of 5-40 d, respectively. In BNR, the N2O emission occurred
      mainly during the aerobic phase and its emission ratio decreased with increasing
      SRTs. The ratio between the N2O-N emission and the removed ammonium nitrogen in
      the aerobic phase was 5%, 3%, 1.8% and 0.8% at the SRT of 5 d, 10 d, 20 d and 40
      d, respectively. With low concentrations of dissolved oxygen and high
      concentrations of oxidized nitrogen, the N2O emission was significantly
      accelerated due to heterotrophic denitrification activities.

PMID- 24681557
TI  - Protein cocrystallization molecules originating from in vitro selected
      macrocyclic peptides.
AB  - Transmembrane proteins are intractable crystallization targets due to their low
      solubility and their substantial hydrophobic outer surfaces must be enclosed
      within a partial micelle composed of detergents to avoid aggregation.
      Unfortunately, encapsulation within a partial micelle diminishes specific protein
      to-protein contacts needed for crystal lattice formation. In addition, the high
      conformational flexibility of certain transmembrane proteins reduces sample
      homogeneity causing difficulty in crystallization. Cocrystallization ligands,
      based on either antibody scaffolds or other proteinaceous non-antibody scaffolds,
      have greatly facilitated the crystallization of transmembrane proteins. Recently,
      in vitro selected macrocyclic peptide ligands have been shown to facilitate
      protein crystallization as well. In this review, we discuss selection strategies
      used for the discovery of macrocyclic peptide ligands and the three-dimensional
      crystal structure of the transporter PfMATE in complex with in vitro selected
      macrocyclic peptides. 

PMID- 24681558
TI  - Family carer perspectives of acute hospital care following a diagnosis of motor
      neuron disease: a qualitative secondary analysis.
AB  - OBJECTIVES: The multifaceted nature of the problems faced by someone with motor
      neuron disease requires a knowledgeable multidisciplinary team approach. Where
      available, generally, such services are only provided on an outpatient basis,
      meaning that hospitalised patients are frequently admitted to non-specialist
      wards where understanding of their needs is limited. Little is known regarding
      the inpatient care received by patients. Our objective was to address this by
      exploring the experience of hospitalisation following a diagnosis of motor neuron
      disease from the perspective of family carers of those diagnosed with the
      illness. METHOD: This was a qualitative secondary analysis of pre-existing data
      from two previously published, separately conducted, qualitative studies. The
      study involved interview data from 18 bereaved carers and 3 current carers of
      family members diagnosed with motor neuron disease in Northwest England. RESULTS:
      The findings reveal dissatisfaction with the inpatient care received, which
      impacted negatively not only on patient and carer enthusiasm for future hospital
      admissions but also on carer bereavement. CONCLUSIONS: Patients with motor neuron
      disease have specialist needs that are not always met during hospital admission,
      particularly to non-specialist units. The inpatient care provided for these
      patients must be improved as must the knowledge and understanding of the illness
      among healthcare professionals who treat them.

PMID- 24681559
TI  - Caring for those who die at home: the use and validation of 'Care Of the Dying
      Evaluation' (CODE) with bereaved relatives.
AB  - BACKGROUND: As well as facilitating patients' wish to die at home, evaluating
      quality of care in this setting is essential. Postbereavement surveys with family
      members represent one assessment method. 'Care Of the Dying Evaluation' (CODE) is
      a 40-item self-completion postbereavement questionnaire, based on the key
      components of best practice for care of the dying. AIM: To assess the validity
      and reliability of CODE by conducting: cognitive 'think aloud' interviews; test
      retest analysis; and assessing internal consistency and construct validity of
      three key composite scales. DESIGN: Postbereavement survey to next-of-kin (NOK).
      SETTING/PARTICIPANTS: 291 NOK to patients who died at home in Northwest England
      from an advanced incurable illness were invited to complete the CODE
      questionnaire. Additionally, potential participants were asked to undertake a
      cognitive interview and/or complete CODE for a second time a month later.
      RESULTS: 72 bereaved relatives (24.7% response rate) returned the completed CODE
      questionnaire, and 25 completed CODE for a second time. 15 cognitive interviews
      were undertaken. All interviewees found CODE sensitively worded and easy to
      understand. Minor revisions were suggested to provide additional clarity. Test
      retest analysis showed all except one question had moderate or good stability.
      Although the ENVIRONMENT scale was not as relevant within the home setting, all
      three key composite scales showed good internal consistency and construct
      validity. CONCLUSIONS: 'CODE' represents a user-friendly, comprehensive outcome
      measure for care of the dying and has been found to be valid and reliable. CODE
      could potentially be used to benchmark individual organisations and identify
      areas for improvement.

PMID- 24681560
TI  - Potential triggers for the holistic assessment of people with severe chronic
      obstructive pulmonary disease: analysis of multiperspective, serial qualitative
      interviews.
AB  - OBJECTIVES: This study explores the narrative accounts of chronic obstructive
      pulmonary disease (COPD) to identify events that potentially could act as
      triggers for provision of supportive and palliative care. Trigger events must
      have meaning for the patient/carer, be visible to professionals, and have value
      in provoking useful actions. METHODS: A purposive sample of people with severe
      COPD, and their informal and professional carers, was recruited from
      primary/secondary care in Scotland. Indepth participant-led interviews allowed
      people to tell their illness story. Events occurring throughout the individual's
      account of the COPD journey were identified, and analysed thematically with
      regard to the meaning, visibility and use as potential triggers. RESULTS: Events
      identified from 92 transcripts (21 patients, 13 family carers, 18 professionals)
      punctuated the disease trajectory and crossed multiprofessional boundaries of
      care. These reflected advancing disease (increasing carer burden, becoming
      housebound, appointment frequency, increasing burden of disease, shifting
      priorities of care) or were an intervention addressing the consequences of
      advancing disease (requesting disabled parking, home adaptations, hospital
      admissions). Despite being meaningful in terms of increasing disability, many
      were invisible to professionals. Others were isolated events symptomatic of
      wider, ongoing disability which could potentially have use as triggers.
      CONCLUSIONS: Meaningful events can be identified within the story of COPD which
      reflect wider needs, are clearly visible to alert professionals, and be of use in
      terms of potentially guiding supportive interventions. To achieve this level of
      usefulness, services will need to promote health and social care integration with
      clear processes to facilitate holistic assessment when a trigger is detected.

PMID- 24681561
TI  - Supramolecular self-assembly of metal-free naphthalocyanine on Au(111).
AB  - The self-assembly of metal-free naphthalocyanine (H2Nc) on the Au(111) surface is
      studied under ultrahigh vacuum conditions at room temperature using a combination
      of scanning tunnelling microscopy (STM), low-energy electron diffraction (LEED)
      and X-ray photoelectron spectroscopy (XPS). The STM measurements reveal that the
      molecules form a well-ordered, defect-free structure with a square-like unit cell
      at monolayer coverage with their molecular plane parallel to the substrate plane.
      The molecular lattice direction is aligned along one of the principal directions
      of the underlying Au(111) substrate while the molecular orientation remains
      unchanged for different domains. XPS measurements show that there is no
      significant difference in the electronic structure of H2Nc between monolayer and
      multilayer coverage. Combining the information obtained from STM, LEED and XPS
      measurements demonstrates that the self-assembled structure of H2Nc on Au(111) is
      mainly stabilized by intermolecular interactions while the molecule-substrate
      interactions are responsible for the rotational alignment of the molecules with
      respect to the principal Au directions. 

PMID- 24681562
TI  - Analysis of crystalline silica in bulk materials.

PMID- 24681563
TI  - [Campaigns for HIV testing, an effective strategy for universal access to
      prevention and treatment? The experience of Burkina Faso].
AB  - OBJECTIVES: Increasing the rate of people who know their HIV status is
      imperative, particularly in sub Saharan Africa, and this requires an assessment
      of strategies for increasing the utilization of testing services. This article
      discusses the relevance, feasibility, and effectiveness of national screening
      campaigns conducted between 2006 and 2010 in Burkina Faso. METHODOLOGY: An
      analysis of all data regarding testing uptake from 2006 to 2010 was conducted,
      along with interviews of key participants in the process. RESULTS: The results
      show that the 8 screening campaigns led to HIV testing of 487,727 people, that
      is, 50% of the total number of people tested and 24.6 % of HIV+ people diagnosed
      during this period. Campaigns succeeded in testing populations that are difficult
      to reach (especially young people), at a low cost. CONCLUSIONS: This strategy is
      relevant and useful for identifying HIV+ people. Its utility for HIV prevention
      campaigns requires further study. Campaigns are effective and cost-effective even
      in this country with a low disease prevalence. These results underline the
      importance of the synergy between community-based organizations and health
      services in the provision of counseling and testing.

PMID- 24681564
TI  - The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by
      antagonizing signaling via the receptor for IL-6.
AB  - The physiological functions of members of the tumor-necrosis factor (TNF)
      receptor (TNFR)-associated factor (TRAF) family in T cell immunity are not well
      understood. We found that in the presence of interleukin 6 (IL-6), naive TRAF5
      deficient CD4(+) T cells showed an enhanced ability to differentiate into the
      TH17 subset of helper T cells. Accordingly, TH17 cell-associated experimental
      autoimmune encephalomyelitis (EAE) was greatly exaggerated in Traf5(-/-) mice.
      Although it is normally linked with TNFR signaling pathways, TRAF5 constitutively
      associated with a cytoplasmic region in the signal-transducing receptor gp130
      that overlaps with the binding site for the transcription activator STAT3 and
      suppressed the recruitment and activation of STAT3 in response to IL-6. Our
      results identify TRAF5 as a negative regulator of the IL-6 receptor signaling
      pathway that limits the induction of proinflammatory CD4(+) T cells that require
      IL-6 for their development. 

PMID- 24681565
TI  - CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1
      and HDAC2.
AB  - Molecular mechanisms that maintain lineage integrity of helper T cells are
      largely unknown. Here we show histone deacetylases 1 and 2 (HDAC1 and HDAC2) as
      crucial regulators of this process. Loss of HDAC1 and HDAC2 during late T cell
      development led to the appearance of major histocompatibility complex (MHC) class
      II-selected CD4(+) helper T cells that expressed CD8-lineage genes such as Cd8a
      and Cd8b1. HDAC1 and HDAC2-deficient T helper type 0 (TH0) and TH1 cells further
      upregulated CD8-lineage genes and acquired a CD8(+) effector T cell program in a
      manner dependent on Runx-CBFbeta complexes, whereas TH2 cells repressed features
      of the CD8(+) lineage independently of HDAC1 and HDAC2. These results demonstrate
      that HDAC1 and HDAC2 maintain integrity of the CD4 lineage by repressing Runx
      CBFbeta complexes that otherwise induce a CD8(+) effector T cell-like program in
      CD4(+) T cells. 

PMID- 24681568
TI  - The unnatural racial naturalism.
AB  - In the recent article, "Against the New Racial Naturalism", Adam Hochman (2013,
      p. 332) argues that new racial naturalists have been too hasty in their racial
      interpretation of genetic clustering results of human populations. While Hochman
      makes a number of good points, the purpose of this paper is to show that
      Hochman's attack on new racial naturalists is misguided due to his definition of
      'racial naturalism'. Thus, I will show that Hochman's critique is merely a
      consequence of an unnatural interpretation of racial naturalism.

PMID- 24681566
TI  - Signaling by IL-6 promotes alternative activation of macrophages to limit
      endotoxemia and obesity-associated resistance to insulin.
AB  - Obesity and resistance to insulin are closely associated with the development of
      low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated
      inflammation; however, its role in this context remains controversial. Here we
      found that mice with an inactivated gene encoding the IL-6Ralpha chain of the
      receptor for IL-6 in myeloid cells (Il6ra(Deltamyel) mice) developed exaggerated
      deterioration of glucose homeostasis during diet-induced obesity, due to enhanced
      resistance to insulin. Tissues targeted by insulin showed increased inflammation
      and a shift in macrophage polarization. IL-6 induced expression of the receptor
      for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous
      manner. Il6ra(Deltamyel) mice were resistant to IL-4-mediated alternative
      polarization of macrophages and exhibited enhanced susceptibility to
      lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via
      IL-6 as an important determinant of the alternative activation of macrophages and
      assign an unexpected homeostatic role to IL-6 in limiting inflammation. 

PMID- 24681567
TI  - Acute pretreatment with chloroquine attenuates renal I/R injury in rats.
AB  - BACKGROUND: Acute kidney injury (AKI) still remains an unresolved problem in
      pharmacotherapy and renal inflammation is a major factor in its development.
      Chloroquine, a well-known antimalarial drug, posses pleitropic effects as well:
      antiinflammatory, anticoagulant and vascular actions. The effects of chloroquine
      on renal function may involve significant increase in urine flow rate, glomerular
      filtration rate and sodium excretion, as well as stimulation of nitric oxide
      synthase. However, its role in experimental models of renal I/R injury is
      unknown. We aimed to analyze the acute effects of a single-dose intravenous
      chloroquine administered at three different times in the experimental model of
      I/R injury in rat. METHODS: Rats were subjected to bilateral renal ischemia (45
      min) followed by reperfusion with saline lasting 4 hours. Chloroquine was
      administered in doses of 0.3 mg/kg i.v. and 3 mg/kg i.v. 30 min before ischemia,
      30 min before reperfusion and 5 min before reperfusion. Selected a hemodynamic,
      biochemical and morphological parameters were followed in the Sham-operated
      animals and rats subjected to I/R injury and pretreated with saline or
      chloroquine. RESULTS: Chloroquine (0.3 and 3 mg/kg, i.v.) protected the I/R
      injured kidney in an U-shaped manner. Both doses were protective regarding
      biochemical and histological markers of the I/R injury (serum urea, creatinine
      and fractional excretion of sodium, as well as total histological score, tubular
      necrosis score and KIM-1 staining score) (P<0.05 vs. corresponding controls, i.e.
      rats subjected to I/R injury and treated with saline only). The protective
      effects of the lower dose of chloroquine were more profound. Time-related
      differences between pretreatments were not observed (P>0.05, all). CONCLUSION:
      Our study shows for the first time that a single dose of chloroquine (0.3 mg/kg
      i.v.) could afford significant protection of the injured rat kidney.

PMID- 24681569
TI  - Virucidal effect of commercially available disinfectants on equine group A
      rotavirus.
AB  - Although many disinfectants are commercially available in the veterinary field,
      information on the virucidal effects of disinfectants against equine group A
      rotavirus (RVA) is limited. We evaluated the performance of commercially
      available disinfectants against equine RVA. Chlorine- and iodine-based
      disinfectants showed virucidal effects, but these were reduced by the presence of
      organic matter. Glutaraldehyde had a virucidal effect regardless of the presence
      of organic matter, but the effect was reduced by low temperature or short
      reaction time, or both. Benzalkonium chloride had the greatest virucidal effect
      among the three quaternary ammonium compounds examined, but its effect was
      reduced by the presence of organic matter or by low temperature or a short
      reaction time. These findings will be useful for preventing the spread of equine
      RVA infection. 

PMID- 24681570
TI  - Updating of attentional and premotor allocation resources as function of previous
      trial outcome.
AB  - The neural bases of the inter-trial validity/invalidity sequential effects in a
      visuo-auditory modified version of the Central Cue Posner's Paradigm (CCPP) are
      analyzed by means of Early Directing Attention Negativity (EDAN), Contingent
      Negative Variation (CNV) and Lateralized Readiness Potential (LRP). ERPs results
      indicated an increase in CNV and LRP in trials preceded by valid trials compared
      to trials preceded by invalid trials. The CNV and LRP pattern would be highly
      related to the behavioral pattern of lower RTs and higher number of anticipations
      in trials preceded by valid with respect to trials preceded by invalid trials.
      This effect was not preceded by a modulation of the EDAN as a result of the
      previous trial condition. The results suggest that there is a trial-by-trial
      dynamic modulation of the attentional system as a function of the validity
      assigned to the cue, in which conditional probabilities between cue and target
      are continuously updated. 

PMID- 24681571
TI  - Arm exercise myocardial perfusion imaging for prognostication of long-term
      outcome.
AB  - INTRODUCTION: Pharmacologic evaluations constitute >=50% of imaging stress tests,
      but exercise reduces adverse effects, improves myocardial perfusion imaging (MPI)
      quality and diagnostic results, and provides powerful prognostic and clinically
      important information on exercise capacity and cardiovascular responses to the
      relevant physiologic stress of exercise. Thus, our purpose was to determine
      whether arm exercise and MPI variables predict long-term outcome in patients who
      cannot perform leg exercise. METHODS: We performed arm exercise MPI stress tests
      in 253 consecutive patients age 64.5 (10.7) yr (mean (SD)) from 1997 to 2002 and
      investigated associations of arm exercise and abnormal MPI variables with all
      cause mortality, myocardial infarction (MI), coronary artery bypass grafting
      (CABG), and percutaneous coronary intervention (PCI) during follow-up of 12.0
      (1.3) yr. RESULTS: There were 156 deaths (61.7%), 47 patients suffered MI
      (18.6%), 24 underwent CABG (9.5%), and 50 had PCI (19.8%). Arm exercise capacity
      and delta HR (peak - resting) were strongly associated with survival after
      adjustment for significant demographic and clinical variables (Cox multivariate P
      < 0.0001 and 0.001, respectively). MPI was abnormal in 157 patients (62.1%). An
      abnormal arm exercise MPI was borderline predictive of mortality by Cox analysis
      (71.8% vs 46.4% for normal study; univariate P < 0.0001; multivariate P = 0.07)
      but resulted in 58% relative incremental integrated discrimination improvement
      over clinical variables for predicting death. Perfusion defect size also strongly
      predicted mortality (Cox multivariate P = 0.003). An abnormal arm exercise MPI
      study, perfusion defect type, and size all prognosticated PCI (all P <= 0.03) but
      not MI or CABG. CONCLUSIONS: Arm exercise MPI is a valuable approach for outcome
      prediction in patients unable to perform leg exercise.

PMID- 24681572
TI  - Nitrate supplementation enhances the contractile properties of human skeletal
      muscle.
AB  - PURPOSE: Dietary nitrate supplementation positively affects cardiovascular
      function at rest and energy metabolism during exercise in humans and has recently
      also been reported to markedly enhance the in vitro contractile properties of
      mouse fast-twitch muscle. The aim of this study was to investigate the effects of
      short-term nitrate supplementation on the in vivo contractile properties of the
      skeletal muscle and voluntary muscle function of humans. METHODS: In a double
      blind, randomized, crossover design, 19 healthy untrained men (21 +/- 3 yr)
      ingested a nitrate-rich concentrated beetroot juice (NIT; nitrate dosage,
      approximately 9.7 mmol.d) and a placebo (PLA) for seven consecutive days. After
      the last supplementation dose, force was recorded while participants completed a
      series of voluntary and involuntary (electrically evoked) unilateral isometric
      contractions of the knee extensors. RESULTS: NIT enhanced the peak force response
      to low-frequency electrical stimulation, as follows: maximal twitch (NIT, 149 +/-
      41 N, vs PLA, 138 +/- 37 N; P = 0.008; effect size, r (ES) = 0.56) and submaximal
      1- to 20-Hz contractions (5%-10%, ES = 0.53-0.63). Whereas explosive (rising
      phase) force production during the first 50 ms of evoked maximal twitch and octet
      contractions (eight electrical impulses at 300 Hz) was also 3%-15% greater after
      NIT compared with that after PLA (P = 0.023-0.048, ES = 0.52-0.59), explosive
      voluntary force remained similar (P = 0.510, ES = 0.16). Maximum voluntary force
      was also unchanged after NIT (P = 0.539, ES = 0.15). CONCLUSIONS: These results
      indicate that 7 d of dietary nitrate supplementation enhanced the in vivo
      contractile properties of the human skeletal muscle. Specifically, nitrate
      supplementation improved excitation-contraction coupling at low frequencies of
      stimulation and enhanced evoked explosive force production but did not affect
      maximum or explosive voluntary force production in untrained individuals.

PMID- 24681573
TI  - Co-crystallization phase transformations in all pi-conjugated block copolymers
      with different main-chain moieties.
AB  - Driven by molecular affinity and balance in the crystallization kinetics, the
      ability to co-crystallize dissimilar yet self-crystallizable blocks of a block
      copolymer (BCP) into a uniform domain may strongly affect its phase diagram. In
      this study, we synthesize a new series of crystalline and monodisperse all-pi
      conjugated poly(2,5-dihexyloxy-p-phenylene)-b-poly(3-(2-ethylhexyl)thiophene)
      (PPP-P3EHT) BCPs and investigate this multi-crystallization effect. Despite
      vastly different side-chain and main-chain structures, PPP and P3EHT blocks are
      able to co-crystallize into a single uniform domain comprising PPP and P3EHT main
      chains with mutually interdigitated side-chains spaced in-between. With
      increasing P3EHT fraction, PPP-P3EHTs undergo sequential phase transitions and
      form hierarchical superstructures including predominately PPP nanofibrils, co
      crystalline nanofibrils, a bilayer co-crystalline/pure P3EHT lamellar structure,
      a microphase-separated bilayer PPP-P3EHT lamellar structure, and finally P3EHT
      nanofibrils. In particular, the presence of the new co-crystalline lamellar
      structure is the manifestation of the interaction balance between self
      crystallization and co-crystallization of the dissimilar polymers on the
      resulting nanostructure of the BCP. The current study demonstrates the co
      crystallization nature of all-conjugated BCPs with different main-chain moieties
      and may provide new guidelines for the organization of pi-conjugated BCPs for
      future optoelectronic applications. 

PMID- 24681575
TI  - Racial residential segregation and preterm birth: built environment as a
      mediator.
AB  - BACKGROUND: Racial residential segregation has been associated with preterm
      birth. Few studies have examined mediating pathways, in part because, with binary
      outcomes, indirect effects estimated from multiplicative models generally lack
      causal interpretation. We develop a method to estimate additive-scale natural
      direct and indirect effects from logistic regression. We then evaluate whether
      segregation operates through poor-quality built environment to affect preterm
      birth. METHODS: To estimate natural direct and indirect effects, we derive risk
      differences from logistic regression coefficients. Birth records (2000-2008) for
      Durham, North Carolina, were linked to neighborhood-level measures of racial
      isolation and a composite construct of poor-quality built environment. We
      decomposed the total effect of racial isolation on preterm birth into direct and
      indirect effects. RESULTS: The adjusted total effect of an interquartile increase
      in racial isolation on preterm birth was an extra 27 preterm events per 1000
      births (risk difference = 0.027 [95% confidence interval = 0.007 to 0.047]). With
      poor-quality built environment held at the level it would take under isolation at
      the 25th percentile, the direct effect of an interquartile increase in isolation
      was 0.022 (-0.001 to 0.042). Poor-quality built environment accounted for 35%
      (11% to 65%) of the total effect. CONCLUSION: Our methodology facilitates the
      estimation of additive-scale natural effects with binary outcomes. In this study,
      the total effect of racial segregation on preterm birth was partially mediated by
      poor-quality built environment.

PMID- 24681574
TI  - Interferon-gamma induces senescence in normal human melanocytes.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) plays an important role in the
      proceedings of vitiligo through recruiting lymphocytes to the lesional skin.
      However, the potential effects of IFN-gamma on skin melanocytes and the
      subsequent contribution to the vitiligo pathogenesis are still unclear.
      OBJECTIVE: To investigate the effects of IFN-gamma on viability and cellular
      functions of melanocytes. METHODS: Primary human melanocytes were treated with
      IFN-gamma. Cell viability, apoptosis, cell cycle melanin content and
      intracellular reactive oxygen species (ROS) level were measured. mRNA expression
      was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock
      protein 70 (HSP-70) was monitored by ELISA. beta-galactosidase staining was
      utilized to evaluate melanocyte senescence. RESULTS: Persistent IFN-gamma
      treatment induced viability loss, apoptosis, cell cycle arrest and senescence in
      melanocytes. Melanocyte senescence was characterized as the changes in
      pigmentation and morphology, as well as the increase of beta-galactosidase
      activity. Increase of p21Cip1/Waf1 protein was evident in melanocytes after IFN
      gamma treatment. IFN-gamma induction of senescence was attenuated by siRNAs
      against p21, Janus kinase 2 (JAK2) or signal transducer and activator of
      transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin
      alpha. IFN-gamma treatment increased the accumulation of intracellular ROS in
      melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited
      IFN-gamma induced p21 expression and melanocyte senescence. IL-6 and HSP-70
      release was significantly induced by IFN-gamma treatment, which was largely
      inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed
      in senescent melanocytes. CONCLUSION: IFN-gamma can induce senescence in
      melanocytes and consequently enhance their immuno-competency, leading to a
      vitiligo-prone milieu.

PMID- 24681576
TI  - Methodological challenges in mendelian randomization.
AB  - We give critical attention to the assumptions underlying Mendelian randomization
      analysis and their biological plausibility. Several scenarios violating the
      Mendelian randomization assumptions are described, including settings with
      inadequate phenotype definition, the setting of time-varying exposures, the
      presence of gene-environment interaction, the existence of measurement error, the
      possibility of reverse causation, and the presence of linkage disequilibrium.
      Data analysis examples are given, illustrating that the inappropriate use of
      instrumental variable techniques when the Mendelian randomization assumptions are
      violated can lead to biases of enormous magnitude. To help address some of the
      strong assumptions being made, three possible approaches are suggested. First,
      the original proposal of Katan (Lancet. 1986;1:507-508) for Mendelian
      randomization was not to use instrumental variable techniques to obtain estimates
      but merely to examine genotype-outcome associations to test for the presence of
      an effect of the exposure on the outcome. We show that this more modest goal and
      approach can circumvent many, though not all, the potential biases described.
      Second, we discuss the use of sensitivity analysis in evaluating the consequences
      of violations in the assumptions and in attempting to correct for those
      violations. Third, we suggest that a focus on negative, rather than positive,
      Mendelian randomization results may turn out to be more reliable. 

PMID- 24681577
TI  - Meat intake and reproductive parameters among young men.
AB  - BACKGROUND: In the United States, anabolic sex steroids are administered to
      cattle for growth promotion. There is concern regarding the reproductive
      consequences of this practice in men who eat beef. We investigated whether meat
      consumption was associated with semen quality parameters and reproductive hormone
      levels in young men. METHODS: Semen samples were obtained from 189 men aged 18-22
      years. Diet was assessed with a previously validated food frequency
      questionnaire. We used linear regression to analyze the cross-sectional
      associations of meat intake with semen quality parameters and reproductive
      hormones while adjusting for potential confounders. RESULTS: There was an inverse
      relation between processed red meat intake and total sperm count. The adjusted
      relative differences in total sperm counts for men in increasing quartiles of
      processed meat intake were 0 (ref), -3 (95% confidence interval = -67 to 37), -14
      (-82 to 28), and -78 (-202 to -5) million (test for trend, P = 0.01). This
      association was strongest among men with abstinence time less than 2 days and was
      driven by a strong inverse relation between processed red meat intake and
      ejaculate volume (test for trend, P = 0.003). CONCLUSIONS: In our population of
      young men, processed meat intake was associated with lower total sperm count. We
      cannot distinguish whether this association is because of residual confounding by
      abstinence time or represents a true biological effect.

PMID- 24681578
TI  - Correlative scanning-transmission electron microscopy reveals that a chimeric
      flavivirus is released as individual particles in secretory vesicles.
AB  - The intracellular morphogenesis of flaviviruses has been well described, but
      flavivirus release from the host cell remains poorly documented. We took
      advantage of the optimized production of an attenuated chimeric yellow
      fever/dengue virus for vaccine purposes to study this phenomenon by microscopic
      approaches. Scanning electron microscopy (SEM) showed the release of numerous
      viral particles at the cell surface through a short-lived process. For
      transmission electron microscopy (TEM) studies of the intracellular
      ultrastructure of the small number of cells releasing viral particles at a given
      time, we developed a new correlative microscopy method: CSEMTEM (for correlative
      scanning electron microscopy - transmission electron microscopy). CSEMTEM
      analysis suggested that chimeric flavivirus particles were released as individual
      particles, in small exocytosis vesicles, via a regulated secretory pathway. Our
      morphological findings provide new insight into interactions between flaviviruses
      and cells and demonstrate that CSEMTEM is a useful new method, complementary to
      SEM observations of biological events by intracellular TEM investigations. 

PMID- 24681579
TI  - Epidural catheter design: history, innovations, and clinical implications.
AB  - Epidural catheters have evolved during the past several decades, as clinicians
      and manufacturers have sought to influence the quality of analgesia and
      anesthesia and reduce the incidence of catheter-related complications. This
      evolution has allowed a transformation from single-shot to continuous-infusion
      techniques and resulted in easier passage into the epidural space, more extensive
      medication distribution, and ultimately, improved patient satisfaction.
      Particular catheter features, including the materials used, tip design, and
      orifice number and arrangement, have been associated with specific outcomes and
      provide direction for future development. 

PMID- 24681580
TI  - Inhibition of the ubiquitin-proteasome pathway does not protect against
      ventilator-induced accelerated proteolysis or atrophy in the diaphragm.
AB  - BACKGROUND: Mechanical ventilation (MV) is a life-saving intervention in patients
      with acute respiratory failure. However, prolonged MV results in ventilator
      induced diaphragm dysfunction (VIDD), a condition characterized by both diaphragm
      fiber atrophy and contractile dysfunction. Previous work has shown that calpain,
      caspase-3, and the ubiquitin-proteasome pathway (UPP) are all activated in the
      diaphragm during prolonged MV. However, although it is established that both
      calpain and caspase-3 are important contributors to VIDD, the role that the UPP
      plays in the development of VIDD remains unknown. These experiments tested the
      hypothesis that inhibition of the UPP will protect the diaphragm against VIDD.
      METHODS: The authors tested this prediction in an established animal model of MV
      using a highly specific UPP inhibitor, epoxomicin, to prevent MV-induced
      activation of the proteasome in the diaphragm (n = 8 per group). RESULTS: The
      results of this study reveal that inhibition of the UPP did not prevent
      ventilator-induced diaphragm muscle fiber atrophy and contractile dysfunction
      during 12 h of MV. Also, inhibition of the UPP does not affect MV-induced
      increases in calpain and caspase-3 activity in the diaphragm. Finally,
      administration of the proteasome inhibitor did not protect against the MV-induced
      increases in the expression of the E3 ligases, muscle ring finger-1 (MuRF1), and
      atrogin-1/MaFbx. CONCLUSION: Collectively, these results indicate that proteasome
      activation does not play a required role in VIDD development during the first 12
      h of MV.

PMID- 24681581
TI  - Temporal structure coding with and without awareness.
AB  - In order to interpret a constantly changing environment, visual events far apart
      in space and time must be integrated into a unified percept. While spatial
      properties of invisible signals are known to be encoded without awareness, the
      fate of temporal properties remains largely unknown. Here, we probed temporal
      integration for two distinct motion stimuli that were either visible or rendered
      invisible using continuous flash suppression. We found that when invisible, both
      the direction of apparent motion and the gender of point-light walkers were
      processed only when defined across short time periods (i.e., respectively 100 ms
      and 1000 ms). This limitation was not observed under full visibility. These
      similar findings at two different hierarchical levels of processing suggest that
      temporal integration windows shrink in the absence of perceptual awareness. We
      discuss this phenomenon as a key prediction of the global neuronal workspace and
      the information integration theories of consciousness.

PMID- 24681582
TI  - Swelling and shrinking properties of thermo-responsive polymeric ionic liquid
      hydrogels with embedded linear pNIPAAM.
AB  - In this study, varying concentrations of linear pNIPAAM have been incorporated
      for the first time into a thermo-responsive polymeric ionic liquid (PIL)
      hydrogel, namely tributyl-hexyl phosphonium 3-sulfopropylacrylate (P-SPA), to
      produce semi-interpenetrating polymer networks. The thermal properties of the
      resulting hydrogels have been investigated along with their thermo-induced
      shrinking and reswelling capabilities. The semi-interpenetrating networks (IPN)
      hydrogels were found to have improved shrinking and reswelling properties
      compared with their PIL counterpart. At elevated temperatures (50-80  degrees C),
      it was found that the semi-IPN with the highest concentration of hydrophobic
      pNIPAAM exhibited the highest shrinking percentage of ~40% compared to the
      conventional P-SPA, (27%). This trend was also found to occur for the reswelling
      measurements, with semi-IPN hydrogels producing the highest reswelling percentage
      of ~67%, with respect to its contracted state. This was attributed to an increase
      in water affinity due to the presence of hydrophilic pNIPAAM. Moreover, the
      presence of linear pNIPAAM in the polymer matrix leads to improved shrinking and
      reswelling response compared to the equivalent PIL. 

PMID- 24681583
TI  - Seed-specific expression of a lysine-rich protein gene, GhLRP, from cotton
      significantly increases the lysine content in maize seeds.
AB  - Maize seed storage proteins are a major source of human and livestock
      consumption. However, these proteins have poor nutritional value, because they
      are deficient in lysine and tryptophan. Much research has been done to elevate
      the lysine content by reducing zein content or regulating the activities of key
      enzymes in lysine metabolism. Using the naturally lysine-rich protein genes,
      sb401 and SBgLR, from potato, we previously increased the lysine and protein
      contents of maize seeds. Here, we examined another natural lysine-rich protein
      gene, GhLRP, from cotton, which increased the lysine content of transgenic maize
      seeds at levels varying from 16.2% to 65.0% relative to the wild-type. The total
      protein content was not distinctly different, except in the six transgenic lines.
      The lipid and starch levels did not differ substantially in Gossypium hirsutum L.
      lysine-rich protein (GhLRP) transgenic kernels when compared to wild-type. The
      agronomic characteristics of all the transgenic maize were also normal. GhLRP is
      a high-lysine protein candidate gene for increasing the lysine content of maize.
      This study provided a valuable model system for improving maize lysine content. 

PMID- 24681584
TI  - Searching for the perfect wave: the effect of radiofrequency electromagnetic
      fields on cells.
AB  - There is a growing concern in the population about the effects that environmental
      exposure to any source of "uncontrolled" radiation may have on public health.
      Anxiety arises from the controversial knowledge about the effect of
      electromagnetic field (EMF) exposure to cells and organisms but most of all
      concerning the possible causal relation to human diseases. Here we reviewed those
      in vitro and in vivo and epidemiological works that gave a new insight about the
      effect of radio frequency (RF) exposure, relating to intracellular molecular
      pathways that lead to biological and functional outcomes. It appears that a
      thorough application of standardized protocols is the key to reliable data
      acquisition and interpretation that could contribute a clearer picture for
      scientists and lay public. Moreover, specific tuning of experimental and clinical
      RF exposure might lead to beneficial health effects. 

PMID- 24681587
TI  - Physiological and behavioral responses reveal 9-month-old infants' sensitivity to
      pleasant touch.
AB  - Caregiving touch has been shown to be essential for the growth and development of
      human infants. However, the physiological and behavioral mechanisms that underpin
      infants' sensitivity to pleasant touch are still poorly understood. In human
      adults, a subclass of unmyelinated peripheral nerve fibers has been shown to
      respond preferentially to medium-velocity soft brushing. It has been theorized
      that this privileged pathway for pleasant touch is used for close affiliative
      interactions with conspecific individuals, especially between caregivers and
      infants. To test whether human infants are sensitive to pleasant touch, we
      examined arousal (heart rate) and attentional engagement (gaze shifts and
      duration of looks) to varying velocities of brushing (slow, medium, and fast) in
      9-month-old infants. Our results provide physiological and behavioral evidence
      that sensitivity to pleasant touch emerges early in development and therefore
      plays an important role in regulating human social interactions. 

PMID- 24681586
TI  - Testosterone reactivity to provocation mediates the effect of early intervention
      on aggressive behavior.
AB  - We tested the hypotheses that the Fast Track intervention program for high-risk
      children would reduce adult aggressive behavior and that this effect would be
      mediated by decreased testosterone responses to social provocation. Participants
      were a subsample of males from the full trial sample, who during kindergarten had
      been randomly assigned to the 10-year Fast Track intervention or to a control
      group. The Fast Track program attempted to develop children's social competencies
      through child social-cognitive and emotional-coping skills training, peer
      relations coaching, academic tutoring, and classroom management, as well as
      training for parents to manage their child's behavior. At a mean age of 26 years,
      participants responded to laboratory provocations. Results indicated that,
      relative to control participants, men assigned to the intervention demonstrated
      reduced aggression and testosterone reactivity to social provocations. Moreover,
      reduced testosterone reactivity mediated the effect of intervention on aggressive
      behavior, which provides evidence for an enduring biological mechanism underlying
      the effect of early psychosocial intervention on aggressive behavior in
      adulthood. 

PMID- 24681585
TI  - Tug of war between survival and death: exploring ATM function in cancer.
AB  - Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of
      genome stability and plays a central role in the DNA damage response (DDR). The
      deregulation of these pathways is strongly linked to cancer initiation and
      progression as well as to the development of therapeutic approaches. These
      observations, along with reports that identify ATM loss of function as an event
      that may promote tumor initiation and progression, point to ATM as a bona fide
      tumor suppressor. The identification of ATM as a positive modulator of several
      signalling networks that sustain tumorigenesis, including oxidative stress,
      hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation,
      raise the question of whether ATM function in cancer may be more complex. This
      review aims to give a complete overview on the work of several labs that links
      ATM to the control of the balance between cell survival, proliferation and death
      in cancer. 

PMID- 24681588
TI  - Sodium fluoride activates ERK and JNK via induction of oxidative stress to
      promote apoptosis and impairs ovarian function in rats.
AB  - The toxicity of sodium fluoride (NaF) to female fertility is currently
      recognized; however, the mechanisms are unclear. Previously, we reported a
      reduction in successful pregnancy rates, ovarian atrophy and dysfunction
      following exposure to NaF. The purpose of this study was to elucidate the
      underlying molecular mechanisms. Female Sprague-Dawley rats (10 rats/group)
      received 100 or 200mg/L NaF in their drinking water for 6 months or were assigned
      to an untreated control group. Apoptotic indices and oxidative stress indicators
      in blood and ovarian tissue were analyzed following sacrifice. The results
      confirmed the NaF-induced ovarian apoptosis, with concomitant activation of
      oxidative stress. Further investigations in ovarian granular cells showed that
      exposure to NaF activated extracellular regulated protein kinase (ERK) and c-Jun
      NH2 kinase (JNK), disrupting the ERK and JNK signaling pathways, while p38 and
      PI3K remained unchanged. These data demonstrated that oxidative stress may play a
      key role in NaF-induced ovarian dysfunction by activating the apoptotic ERK and
      JNK signaling pathways. 

PMID- 24681589
TI  - Modification of cyanobacterial bloom-derived biomass using potassium permanganate
      enhanced the removal of microcystins and adsorption capacity toward cadmium (II).
AB  - Cyanobacterial biomass shows high adsorption capacity toward heavy metal ions.
      However, the cyanotoxins in the cyanobacterial biomass inhibit its application in
      heavy metals removal. In order to safely and effectively remove Cd(II) from water
      using cyanobacterial bloom-derived biomass (CBDB), KMnO4 was used to modify CBDB.
      The results indicated that the microcystins in the CBDB were successfully removed
      by KMnO4. Potassium permanganate oxidation caused the transformation of hydroxyl
      to carboxyl on the CBDB, and formed manganese dioxide on the surface of CBDB. The
      oxidized CBDB showed higher adsorption capacity toward Cd(II) than that of
      unoxidized treatment. The optimal KMnO4 concentration for increasing the
      adsorption capacity of CBDB toward Cd(II) was 0.2g/L. The adsorption isotherm of
      Cd(II) by oxidized- or unoxidized-CBDB was well fitted by Langmuir model,
      indicating that the adsorption of Cd(II) by CBDB was monolayer adsorption. The
      desorption ratio of Cd(II) from oxidized CBDB was higher than that from
      unoxidized CBDB in the desorption process using NH4NO3 and EDTA as desorbent. The
      results presented in this study suggest that KMnO4 modified CBDB may be used as a
      safe and high efficient adsorbent in Cd(II) removal from water. 

PMID- 24681590
TI  - Reduction of hexavalent chromium using Aerva lanata L.: elucidation of reduction
      mechanism and identification of active principles.
AB  - The effluent discharge treatment for controlling the environment from non
      biodegradable metal contaminants using plant extract is an efficient technique.
      The reduction of hexavalent chromium by abundantly available weed, Aerva lanata
      L. was investigated using batch equilibrium technique. The variables studied were
      Cr(VI) concentration, Aerva lanata L. dose, contact time, pH, temperature and
      agitation speed. Cyclic voltammetry and ICP-MS analysis confirmed the reduction
      of Cr(VI) to Cr(III). Electrochemical analysis proved that, the chromium has not
      been degraded and the valency of the chromium has only been changed. ICP-MS
      analysis shows that 100ng/L of hexavalent chromium was reduced to 97.01ng/L
      trivalent chromium. These results suggest that components present in the Aerva
      lanata L. are responsible for the reduction of Cr(VI) to Cr(III). The prime
      components ferulic acid, kaempherol and beta-carboline present in the Aerva
      lanata L. may be responsible for the reduction of Cr(VI) as evident from LC-MS
      analysis. 

PMID- 24681591
TI  - Rare earth elements recycling from waste phosphor by dual hydrochloric acid
      dissolution.
AB  - This paper is a comparative study of recycling rare earth elements from waste
      phosphor, which focuses on the leaching rate and the technical principle. The
      traditional and dual dissolution by hydrochloric acid (DHA) methods were
      compared. The method of dual dissolution by hydrochloric acid has been developed.
      The Red rare earth phosphor (Y0.95Eu0.05)2O3 in waste phosphor is dissolved
      during the first step of acid leaching, while the Green phosphor
      (Ce0.67Tb0.33MgAl11O19) and the Blue phosphor (Ba0.9Eu0.1MgAl10O17) mixed with
      caustic soda are obtained by alkali sintering. The excess caustic soda and NaAlO2
      are removed by washing. The insoluble matter is leached by the hydrochloric acid,
      followed by solvent extraction and precipitation (the DHA method). In comparison,
      the total leaching rate of the rare earth elements was 94.6% by DHA, which is
      much higher than 42.08% achieved by the traditional method. The leaching rate of
      Y, Eu, Ce and Tb reached 94.6%, 99.05%, 71.45%, and 76.22%, respectively. DHA can
      decrease the consumption of chemicals and energy. The suggested DHA method is
      feasible for industrial applications. 

PMID- 24681593
TI  - Garnet-type solid-state fast Li ion conductors for Li batteries: critical review.
AB  - Batteries are electrochemical devices that store electrical energy in the form of
      chemical energy. Among known batteries, Li ion batteries (LiBs) provide the
      highest gravimetric and volumetric energy densities, making them ideal candidates
      for use in portable electronics and plug-in hybrid and electric vehicles.
      Conventional LiBs use an organic polymer electrolyte, which exhibits several
      safety issues including leakage, poor chemical stability and flammability. The
      use of a solid-state (ceramic) electrolyte to produce all-solid-state LiBs can
      overcome all of the above issues. Also, solid-state Li batteries can operate at
      high voltage, thus, producing high power density. Various types of solid Li-ion
      electrolytes have been reported; this review is focused on the most promising
      solid Li-ion electrolytes based on garnet-type metal oxides. The first studied Li
      stuffed garnet-type compounds are Li5La3M2O12 (M = Nb, Ta), which show a Li-ion
      conductivity of ~10(-6) at 25  degrees C. La and M sites can be substituted by
      various metal ions leading to Li-rich garnet-type electrolytes, such as
      Li6ALa2M2O12, (A = Mg, Ca, Sr, Ba, Sr0.5Ba0.5) and Li7La3C2O12 (C = Zr, Sn).
      Among the known Li-stuffed garnets, Li6.4La3Zr1.4Ta0.6O12 exhibits the highest
      bulk Li-ion conductivity of 10(-3) S cm(-1) at 25  degrees C with an activation
      energy of 0.35 eV, which is an order of magnitude lower than that of the
      currently used polymer, but is chemically stable at higher temperatures and
      voltages compared to polymer electrolytes. Here, we discuss the chemical
      composition-structure-ionic conductivity relationship of the Li-stuffed garnet
      type oxides, as well as the Li ion conduction mechanism. 

PMID- 24681592
TI  - Rapid removal of copper with magnetic poly-acrylic weak acid resin: quantitative
      role of bead radius on ion exchange.
AB  - A novel magnetic weak acid resin NDMC was self-synthesized for the removal of
      Cu(2+) from aqueous solutions. NDMC showed superior properties on the removal of
      Cu(2+) compared to commercial resins C106 and IRC-748, which was deeply
      investigated by adsorption isotherms and kinetic tests. The equilibrium
      adsorption amount of Cu(2+) onto NDMC (267.2mg/g) was almost twice as large as
      that onto IRC-748 (120.0mg/g). The adsorption kinetics of Cu(2+) onto the three
      resins fitted well with the pseudo-second-order equation. The initial adsorption
      rate h of NDMC was about 4 times that of C106 and nearly 8 times that of IRC-748
      at the initial concentration of 500mg/L. External surface area was determined to
      be the key factor in rate-controlling by further analyzing the adsorption
      thermodynamics, kinetics parameters and physicochemical properties of the resins.
      NDMC resin with the smallest bead radius possessed the largest external surface
      and therefore exhibited the fastest kinetics. The adsorption amount of Cu(2+)
      onto NDMC was not influenced as the concentration of Na(+) increased from 1.0 to
      10.0mM/L. Dilute HCl solution could effectively desorb Cu(2+). NDMC demonstrated
      high stability during 10 adsorption/desorption cycles, showing great potential in
      the rapid removal of Cu(2+) from wastewater. 

PMID- 24681594
TI  - Structural insights into the transport of small molecules across membranes.
AB  - While hydrophobic small molecules often can freely permeate a lipid bilayer, ions
      and other polar molecules cannot and require transporters to mediate their
      transport. Recently, a number of important structures have been reported which
      have advanced our understanding of how membrane protein transporters function to
      transport small molecules. Structures of TbpA/B and HmuUV provided new insight
      into iron uptake by pathogenic bacteria while the structures of NarK, ASBT, and
      VcINDY revealed molecular details about the transport of nitrate, bile acids and
      dicarboxylates, respectively. The structure of the folate ECF transporter
      indicated that the S component likely undergoes a large conformational shift to
      mediate folate transport, while the cellulose synthase/transporter contains an
      elongated translocation pore for passage through the inner membrane.

PMID- 24681595
TI  - [Collection of mollusk intermediate hosts of Schistosoma at two sites in Lampsar
      (Senegal River valley): quantitative reproducibility].
AB  - We studied the number of mollusks collected according to a specific protocol: 2
      samplers prospecting in opposite directions for 1 min 30 s at 10 collection
      points regularly distributed on the site, for a total of 2 times 15 minutes.
      Because of the good reproducibility of the results of these collections, this
      method can be used for quantitative studies. A sampling effect was noted. 

PMID- 24681596
TI  - Differential expression of the main polycyclic aromatic hydrocarbon responsive
      genes in the extrahepatic tissues of mice.
AB  - The hepatic toxic effects, including carcinogenicity and oxidative stress, of
      polycyclic aromatic hydrocarbons (PAHs) have been extensively studied in recent
      years. Previous reports have demonstrated that 3-methylcholanthrene (3MC) is
      capable of altering the expression of aryl hydrocarbon receptor (AHR)-regulated
      genes and antioxidant genes in liver, but little is known about the expression
      patterns in other tissues. To investigate whether similar effects could occur in
      the extrahepatic tissues, adult male ICR mice were received an intraperitoneal
      injection of 100 mg/kg 3MC and then analyzed after 6 and 24 h. We observed that
      the constitutive expression of AHR- and antioxidant-related genes was in a tissue
      specific manner. Moreover, acute 3MC exposure significantly increased the mRNA
      levels of Cyp1a1 and Cyp1b1 in all the lung, kidney and heart. As to antioxidant
      genes, 3MC induced the transcription of glutathione reductase (Gr) in the lung
      and kidney at 24 h and the transcription of glutathione peroxidase 1 (Gpx1) in
      the lung and kidney at 6 and 24 h. Glutathione-S-transferase A1 (Gsta1) was
      significantly reduced in the kidney at 24 h, while no effect was observed in the
      lung and heart. The mRNA levels of NAD(P)H: quinone oxidoreductase 1 (Nqo1) were
      induced by 3MC in all the lung, kidney and heart. Although the constitutive
      expression of catalase (Cat) is very low in the heart, the transcription of Cat
      was significantly induced both at 6 and 24 h. No significant alternation in the
      transcription of glutathione synthetase (Gss), heme oxygenase 1 (Ho-1) and
      superoxide dismutase 1 (Sod1) was observed in all tissues. Taken together, ours
      findings suggested that the expression of AHR- and antioxidant-related genes in a
      tissue-specific manner with or without treatment of a PAH.

PMID- 24681597
TI  - Kindlin-1 controls Wnt and TGF-beta availability to regulate cutaneous stem cell
      proliferation.
AB  - Kindlin-1 is an integrin tail binding protein that controls integrin activation.
      Mutations in the FERMT-1 gene, which encodes for Kindlin-1, lead to Kindler
      syndrome in man, which is characterized by skin blistering, premature skin aging
      and skin cancer of unknown etiology. Here we show that loss of Kindlin-1 in mouse
      keratinocytes recapitulates Kindler syndrome and also produces enlarged and
      hyperactive stem cell compartments, which lead to hyperthickened epidermis,
      ectopic hair follicle development and increased skin tumor susceptibility.
      Mechanistically, Kindlin-1 controls keratinocyte adhesion through beta1-class
      integrins and proliferation and differentiation of cutaneous epithelial stem
      cells by promoting alpha(v)beta(6) integrin-mediated transforming growth factor
      beta (TGF-beta) activation and inhibiting Wnt-beta-catenin signaling through
      integrin-independent regulation of Wnt ligand expression. Our findings assign
      Kindlin-1 the previously unknown and essential task of controlling cutaneous
      epithelial stem cell homeostasis by balancing TGF-beta-mediated growth-inhibitory
      signals and Wnt-beta-catenin-mediated growth-promoting signals.

PMID- 24681598
TI  - Label-free in vivo imaging of myelinated axons in health and disease with
      spectral confocal reflectance microscopy.
AB  - We report a newly developed technique for high-resolution in vivo imaging of
      myelinated axons in the brain, spinal cord and peripheral nerve that requires no
      fluorescent labeling. This method, based on spectral confocal reflectance
      microscopy (SCoRe), uses a conventional laser-scanning confocal system to
      generate images by merging the simultaneously reflected signals from multiple
      lasers of different wavelengths. Striking color patterns unique to individual
      myelinated fibers are generated that facilitate their tracing in dense axonal
      areas. These patterns highlight nodes of Ranvier and Schmidt-Lanterman incisures
      and can be used to detect various myelin pathologies. Using SCoRe we carried out
      chronic brain imaging up to 400 MUm deep, capturing de novo myelination of mouse
      cortical axons in vivo. We also established the feasibility of imaging myelinated
      axons in the human cerebral cortex. SCoRe adds a powerful component to the
      evolving toolbox for imaging myelination in living animals and potentially in
      humans. 

PMID- 24681599
TI  - Net risk reclassification p values: valid or misleading?
AB  - BACKGROUND: The Net Reclassification Index (NRI) and its P value are used to make
      conclusions about improvements in prediction performance gained by adding a set
      of biomarkers to an existing risk prediction model. Although proposed only 5
      years ago, the NRI has gained enormous traction in the risk prediction
      literature. Concerns have recently been raised about the statistical validity of
      the NRI. METHODS: Using a population dataset of 10000 individuals with an event
      rate of 10.2%, in which four biomarkers have no predictive ability, we repeatedly
      simulated studies and calculated the chance that the NRI statistic provides a
      positive statistically significant result. Subjects for training data (n = 420)
      and test data (n = 420 or 840) were randomly selected from the population, and
      corresponding NRI statistics and P values were calculated. For comparison, the
      change in the area under the receiver operating characteristic curve and
      likelihood ratio statistics were calculated. RESULTS: We found that rates of
      false-positive conclusions based on the NRI statistic were unacceptably high,
      being 63.0% in the training datasets and 18.8% to 34.4% in the test datasets.
      False-positive conclusions were rare when using the change in the area under the
      curve and occurred at the expected rate of approximately 5.0% with the likelihood
      ratio statistic. CONCLUSIONS: Conclusions about biomarker performance that are
      based primarily on a statistically significant NRI statistic should be treated
      with skepticism. Use of NRI P values in scientific reporting should be halted.

PMID- 24681600
TI  - A statistical challenge: developing tests for biomarker utility specific to the
      intended use.

PMID- 24681601
TI  - Colorectal cancer control: providing adequate care to those who need it.

PMID- 24681602
TI  - Challenges and possible solutions to colorectal cancer screening for the
      underserved.
AB  - Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. CRC
      incidence and mortality can be reduced through screening. However, in the United
      States, screening participation remains suboptimal, particularly among
      underserved populations such as the uninsured, recent immigrants, and
      racial/ethnic minority groups. Increasing screening rates among underserved
      populations will reduce the US burden of CRC. In this commentary focusing on
      underserved populations, we highlight the public health impact of CRC screening,
      list key challenges to screening the underserved, and review promising approaches
      to boost screening rates. We identify four key policy and research priorities to
      increase screening among underserved populations: 1) actively promote the
      message, "the best test is the one that gets done"; 2) develop and implement
      methods to identify unscreened individuals within underserved population groups
      for screening interventions; 3) develop and implement approaches for organized
      screening delivery; and 4) fund and enhance programs and policies that provide
      access to screening, diagnostic follow-up, and CRC treatment for underserved
      populations. This commentary represents the consensus of a diverse group of
      experts in cancer control and prevention, epidemiology, gastroenterology, and
      primary care from across the country who formed the Coalition to Boost Screening
      among the Underserved in the United States. The group was organized and held its
      first annual working group meeting in conjunction with the World Endoscopy
      Organization's annual Colorectal Cancer Screening Committee meeting during
      Digestive Disease Week 2012 in San Diego, California. 

PMID- 24681603
TI  - Potentiation of colon cancer susceptibility in mice by colonic epithelial PPAR
      delta/beta overexpression.
AB  - BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor
      delta/beta (PPAR-d) is upregulated in human colorectal cancers, but its role in
      colonic tumorigenesis remains controversial. METHODS: We generated a novel mouse
      model of intestinally targeted PPAR-d overexpression to simulate PPAR-d
      upregulation in human colon carcinogenesis. Colon-specific PPAR-d overexpression
      was confirmed by real-time reverse transcription polymerase chain reaction,
      immunoblotting, and activity assays. Mice with and without targeted PPAR-d
      overexpression were tested for azoxymethane (AOM)-induced colonic tumorigenesis.
      Mouse whole-genome transcriptome microarray analyses were performed to identify
      PPAR-d target genes to promote tumorigenesis. We used linear models to test for
      PPAR-d overexpression trend effects on tumor multiplicity. All statistical tests
      were two-sided. RESULTS: Targeted PPAR-d overexpression markedly increased
      colonic tumor incidence (from 0 of 10 wild-type [WT] littermate mice to 9 of 10
      mice [P < .001] in 2 FVB/N background mouse lines [villin-PPAR-d-1 and villin
      PPAR-d-2] at a 5-mg/kg AOM dose) and multiplicity (number of tumors per mouse per
      mg/kg dose of AOM increased from 0.47 [95% confidence interval [CI] = 0.22 to
      0.72] for the WT littermates to 2.15 [95% CI = 1.90 to 2.40] [P < .001] for the
      villin-PPAR-d-1 mice and from 0.44 [95% CI = 0.09 to 0.79] for the WT littermates
      to 1.91 [95% CI = 1.57 to 2.25] [P < .001] for the villin-PPAR-d-2 mice). PPAR-d
      overexpression reversed resistance to AOM-induced colonic tumorigenesis in
      C57BL/6 mice. PPAR-d overexpression modulated expression of several novel PPAR-d
      target genes in normal-appearing colonic epithelial cells of mice with PPAR-d
      overexpression in a pattern that matched the changes in colonic tumors.
      CONCLUSIONS: Our finding that PPAR-d upregulation profoundly enhances
      susceptibility to colonic tumorigenesis should impact the development of
      strategies of molecularly targeting PPAR-d in cancer and noncancerous diseases.

PMID- 24681604
TI  - Pleiotropic associations of risk variants identified for other cancers with lung
      cancer risk: the PAGE and TRICL consortia.
AB  - BACKGROUND: Genome-wide association studies have identified hundreds of genetic
      variants associated with specific cancers. A few of these risk regions have been
      associated with more than one cancer site; however, a systematic evaluation of
      the associations between risk variants for other cancers and lung cancer risk has
      yet to be performed. METHODS: We included 18023 patients with lung cancer and
      60543 control subjects from two consortia, Population Architecture using Genomics
      and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung
      (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were
      previously associated with at least one of 16 non-lung cancer sites. Study
      specific logistic regression results underwent meta-analysis, and associations
      were also examined by race/ethnicity, histological cell type, sex, and smoking
      status. A Bonferroni-corrected P value of 2.5*10(-5) was used to assign
      statistical significance. RESULTS: The breast cancer SNP LSP1 rs3817198 was
      associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95%
      confidence interval [CI] = 1.05 to 1.14; P = 2.8*10(-6)). This association was
      strongest for women with adenocarcinoma (P = 1.2*10(-4)) and not statistically
      significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma
      risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in
      regions previously associated with lung cancer, were associated with increased
      risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1*10(-8)) and
      squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5*10(-5)),
      respectively. CONCLUSIONS: Our findings demonstrate a novel pleiotropic
      association between the breast cancer LSP1 risk region marked by variant
      rs3817198 and lung cancer risk.

PMID- 24681605
TI  - Effect of cytotoxic chemotherapy on markers of molecular age in patients with
      breast cancer.
AB  - BACKGROUND: Senescent cells, which express p16 (INK4a) , accumulate with aging
      and contribute to age-related pathology. To understand whether cytotoxic agents
      promote molecular aging, we measured expression of p16 (INK4a) and other
      senescence markers in breast cancer patients treated with adjuvant chemotherapy.
      METHODS: Blood and clinical information were prospectively obtained from 33 women
      with stage I to III breast cancer at four time points: before anthracycline-based
      chemotherapy, immediately after anthracycline-based chemotherapy, 3 months after
      anthracycline-based chemotherapy, and 12 months after anthracycline-based
      chemotherapy. Expression of senescence markers p16 (INK4a) and ARF mRNA was
      determined using TaqMan quantitative reverse-transcription polymerase chain
      reaction in CD3(+) T lymphocytes, telomere length was determined by Southern
      analysis, and senescence-associated cytokines were determined by enzyme-linked
      immunosorbent assay. Findings were independently assessed in a cross-sectional
      cohort of 176 breast cancer survivors enrolled a median of 3.4 years after
      treatment; 39% previously received chemotherapy. All statistical tests were two
      sided. RESULTS: In prospectively analyzed patients, expression of p16 (INK4a) and
      ARF increased immediately after chemotherapy and remained elevated 12 months
      after treatment. Median increase in log2 p16 (INK4a) was 0.81 (interquartile
      range = 0.28-1.62; Wilcoxon signed-rank P < .001), or a 75% absolute increase in
      expression, equivalent to the increase observed over 14.7 years of chronological
      aging. ARF expression was comparably increased (P < .001). Increased expression
      of p16 (INK4a) and ARF was associated with dose-dense therapy and hematological
      toxicity. Expression of two senescence-associated cytokines (VEGFA and MCP1) was
      durably increased by adjuvant chemotherapy. Telomere length was not affected by
      chemotherapy. In a cross-sectional cohort, prior chemotherapy exposure was
      independently associated with a log2-increase in p16 (INK4a) expression of 0.57
      (repeated measures model, P < .001), comparable with 10.4 years of chronological
      aging. CONCLUSIONS: Adjuvant chemotherapy for breast cancer is gerontogenic,
      inducing cellular senescence in vivo, thereby accelerating molecular aging of
      hematopoietic tissues.

PMID- 24681606
TI  - Co-targeting the MAPK and PI3K/AKT/mTOR pathways in two genetically engineered
      mouse models of schwann cell tumors reduces tumor grade and multiplicity.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that
      occur spontaneously, or from benign plexiform neurofibromas, in the context of
      the genetic disorder Neurofibromatosis Type 1 (NF1). The current standard
      treatment includes surgical resection, high-dose chemotherapy, and/or radiation.
      To date, most targeted therapies have failed to demonstrate effectiveness against
      plexiform neurofibromas and MPNSTs. Recently, several studies suggested that the
      mTOR and MAPK pathways are involved in the formation and progression of MPNSTs.
      Everolimus (RAD001) inhibits the mTOR and is currently FDA approved for several
      types of solid tumors. PD-0325901 (PD-901) inhibits MEK, a component of the MAPK
      pathway, and is currently in clinical trials. Here, we show in vitro than MPNST
      cell lines are more sensitive to inhibition of cellular growth by Everolimus and
      PD-901 than immortalized human Schwann cells. In combination, these drugs
      synergistically inhibit cell growth and induce apoptosis. In two genetically
      engineered mouse models of MPNST formation, modeling both sporadic and NF1
      associated MPNSTs, Everolimus, or PD-901 treatment alone each transiently reduced
      tumor burden and size, and extended lifespan. However, prolonged treatment of
      each single agent resulted in the development of resistance and reactivation of
      target pathways. Combination therapy using Everolimus and PD-901 had synergistic
      effects on reducing tumor burden and size, and increased lifespan. Combination
      therapy allowed persistent and prolonged reduction in signaling through both
      pathways. These data suggest that co-targeting mTOR and MEK may be effective in
      patients with sporadic or NF1-associated MPNSTs. 

PMID- 24681607
TI  - Effects of newly developed chemotherapy regimens, comorbidities, chemotherapy
      related toxicities on the changing patterns of the leading causes of death in
      elderly patients with colorectal cancer.
AB  - BACKGROUND: Abundant evidences have shown that newly developed chemotherapy
      regimens improved 5-year survival rate of colorectal cancer (CRC) patients over
      the past two decades. However, their impact on risk of death from leading causes
      among elderly patients is still poorly understood. PATIENTS AND METHODS: A
      retrospective cohort study of 69 718 elderly CRC patients with their first
      primary tumors in 1992-2009, identified from the 12 areas of Surveillance,
      Epidemiology, and End Results-Medicare linked database with their Medicare claims
      up to 2010. Multivariate Cox regression models were used to assess the effect of
      newly developed chemotherapy regimens, comorbidities, and chemotherapy related
      toxicities on cause-specific death and their temporal patterns among elderly CRC
      patients. RESULTS: The leading causes of death among CRC patients were CRC,
      circulation disorders, and secondary cancers, which accounted for 51.4%, 25%, and
      4.6% of all-cause death, respectively. Patients diagnosed in more recent
      diagnostic time periods were significantly less likely to die of CRC [period 2: 5
      year hazard ratio = 0.94, 95% confidence interval (CI) 0.90-0.97; period 3: 0.86,
      0.83-0.90], circulation disorders (period 2: 0.94, 0.88-1.00; period 3: 0.80,
      0.75-0.87), and more likely to die of secondary cancer (period 3: 1.42, 1.20
      1.68) compared with those diagnosed in period 1. Charlson comorbidities index and
      the selected pre-existing comorbidities were significantly associated with
      increased 5-year risk of death from all three leading causes. Both hematological
      and gastric toxicity were associated with reduced risk of death from CRC and
      circulation disorders. The association between diagnostic time period and risk
      reduction in death from CRC depended on chemotherapy treatment (P < 0.0001).
      Subgroup analyses showed that the chemotherapy-dependent significant risk
      reduction was seen in patients with stage II-III CRC, patients without
      comorbidities, and patients without toxicities (P < 0.0001 for all). CONCLUSION:
      The newly developed chemotherapy regimens were associated with the decreased risk
      of mortality from CRC.

PMID- 24681608
TI  - Immunogenicity of a recombinant Mycobacterium smegmatis vaccine expressing the
      fusion protein CMX in cattle from Goias State, Brazil.
AB  - This study aimed to evaluate the immunogenicity of a recombinant Mycobacterium
      smegmatis vaccine expressing the CMX fusion protein composed of immunodominant
      epitopes Ag85C, MPT51 and HspX of Mycobacterium tuberculosis, which are important
      mycobacteria virulence factors. A group of Nelore heifers that were 10 to 12
      months of age and negative for the tuberculin skin test (TST) were immunized with
      four doses of the recombinant vaccine mc(2)-CMX (M. smegmatis-Ag85C-MPT51-HspX)
      during a period of one year. Before each immunization, blood was collected to
      obtain sera for antibody analysis. Serological analysis demonstrated that mc(2)
      CMX was able to induce a humoral response with increased levels of specific IgG
      antibodies against CMX, despite minimum antibody levels being detected for
      individual Ag85C, MPT51 or HspX recombinant antigens. However, there was no
      significant increase in specific CD4(+) IFN-gamma-positive T cells.
      Lymphadenomegaly was observed in superficial cervical lymph nodes adjacent to the
      site of vaccination among mc(2)-CMX-vaccinated bovines, and the histopathological
      analysis demonstrated follicular hyperplasia without inflammatory infiltrate or
      granuloma formation. Animals remained negative for the TST until the end of the
      experiments, showing no cross-reactivity with the recombinant vaccine and
      tuberculin proteins. We discuss the potential of mc(2)-CMX to induce an immune
      response in cattle. 

PMID- 24681609
TI  - Risk factors for contact lens-induced papillary conjunctivitis associated with
      silicone hydrogel contact lens wear.
AB  - BACKGROUND: Contact lens-induced papillary conjunctivitis (CLPC) continues to be
      a major cause of dropout during extended wear of contact lenses. This
      retrospective study explores risk factors for the development of CLPC during
      extended wear of silicone hydrogel lenses. METHODS: Data from 205 subjects
      enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens study
      wearing lotrafilcon A silicone hydrogel lenses for up to 30 days of continuous
      wear were used to determine risk factors for CLPC in this secondary analysis of
      the main cohort. The main covariates of interest included substantial lens
      associated bacterial bioburden and topographically determined lens base curve-to
      cornea fitting relationships. Additional covariates of interest included history
      of adverse events, time of year, race, education level, gender, and other subject
      demographics. Statistical analyses included univariate logistic regression to
      assess the impact of potential risk factors on the binary CLPC outcome and Cox
      proportional hazards regression to describe the impact of those factors on time
      to-CLPC diagnosis. RESULTS: Across 12 months of follow-up, 52 subjects (25%)
      experienced CLPC. No associations were found between the CLPC development and the
      presence of bacterial bioburden, lens-to-cornea fitting relationships, history of
      adverse events, gender, or race. Contact lens-induced papillary conjunctivitis
      development followed the same seasonal trends as the local peaks in environmental
      allergens. CONCLUSIONS: Lens fit and biodeposits, in the form of lens-associated
      bacterial bioburden, were not associated with the development of CLPC during
      extended wear with lotrafilcon A silicone hydrogel lenses.

PMID- 24681610
TI  - Triple infection keratitis.
AB  - OBJECTIVE: To analyze the demographics, risk factors, and clinical and
      microbiological characteristics of triple infection keratitis. DESIGN:
      Retrospective case series. PARTICIPANTS: Five patients (five eyes) with triple
      infection keratitis were identified. METHODS: Eyes with polymicrobial keratitis
      were identified from January 2002 to December 2010. Only culture-positive cases
      and eyes infected by three different organisms were included. Demographics, risk
      factors, clinical and microbiological characteristics, and treatment outcomes
      were analyzed. MAIN OUTCOME MEASURES: The size of the corneal infiltrate,
      presence of hypopyon, pre- and post-treatment best-corrected visual acuity,
      antibiotic regimen and sensitivity, types of isolated pathogens, duration of
      infection, and treatment outcomes. RESULTS: The mean age was 39 years (SD, +/
      23.4; range, 21-74). Use of topical steroids was the commonest risk factor (80%).
      Multiple risk factors were identified in four eyes. The average size of corneal
      infiltrate was 23.5 mm (SD, +/-35.2; range, 2.08-85.5), and all eyes developed
      hypopyon. A total of 15 organisms belonging to 10 species (bacteria=7, fungi=3)
      were isolated. Pseudomonas aeruginosa and Candida albicans were the most
      frequently isolated bacteria (n=3) and fungi (n=3), respectively. All patients
      had at least one type of fungal isolate. Infection resolved with medical
      treatment in four eyes and one eye had to be eviscerated as the patient developed
      panophthalmitis. The average time taken for infection to resolve was 30 days (SD,
      +/-19.3; range, 13-61). CONCLUSIONS: A high index of suspicion of polymicrobial
      keratitis should be made in patients with multiple and systemic risk factors. Use
      of topical steroid was the most common risk factor. Prolonged course of disease,
      relatively large infiltrate, and presence of hypopyon and fungal isolates are
      typical features of triple infection keratitis.

PMID- 24681611
TI  - Comparative study of repeatability of phenol red thread test versus Schirmer test
      in normal adults in Saudi Arabia.
AB  - OBJECTIVE: To investigate the repeatability of the phenol red thread (PRT) and
      Schirmer tests in healthy Saudi adults. Additionally, we compared the PRT mean
      value with those reported previously because of significant differences between
      Hong Kong-Chinese, Japanese, and US subjects. METHODS: Thirty healthy young Saudi
      adults (7 men and 23 women; 60 eyes) with a mean age of 22.37+/-2.31 years were
      recruited. Participants provided consent and completed a McMonnies questionnaire.
      Dry eye subjects were excluded based on this questionnaire and slit-lamp
      examination. Both eyes of each subject were examined using the PRT and Schirmer
      tests. Each test was repeated three times for each eye, five minutes apart. The
      PRT test was applied first, followed by the Schirmer test 15 minutes later under
      anesthesia to avoid any inconsistency of the measurements due to reflex tears.
      RESULTS: The PRT and Schirmer tests both demonstrated good repeatability with no
      statistically significant differences. There was a poor correlation between the 2
      tests (r=0.286). There was no statistically significant difference between OD and
      OS in the two tests. The mean PRT values in normal Saudi subjects were higher
      than those reported previously for Hong Kong-Chinese, Japanese, and US subjects.
      CONCLUSIONS: Both the PRT and Schirmer tests displayed good repeatability;
      however, there was a poor correlation between the tests, as reported previously.
      The mean PRT value in normal Saudis was higher, when compared with those reported
      previously for other ethnic groups.

PMID- 24681612
TI  - Corneal reshaping and wavefront aberrations during overnight orthokeratology.
AB  - PURPOSE: To investigate changes of corneal thickness at the vertical and
      horizontal meridians and of wavefront aberrations (WA) over a 30-day period of
      overnight myopia orthokeratology (OK) lens wear. METHODS: Sixteen subjects (11
      women, 5 men, 26.3+/-3.2 years) were enrolled and fitted for OK lenses. Long scan
      depth optical coherence tomography was used to measure corneal thickness profiles
      at both horizontal and vertical meridians at baseline and on days 1, 7, and 30
      days. Corneal and ocular WA of a 6-mm pupil were measured and the root-mean
      square (RMS) of the astigmatism, coma, spherical aberration (SA), and total
      higher-order aberrations (HOAs) were determined. RESULTS: During the 30-day
      period, the central cornea thinned in the horizontal and vertical meridians,
      whereas corneal thickening occurred in the temporal, nasal, and inferior mid
      peripheries. In contrast, the cornea thinned in the mid-peripheral superior.
      There were significant increases in RMS for astigmatism, SA, coma, and positive
      horizontal coma during the study period. After OK, there were significant
      positive correlations between the midperipheral-central thickness change
      difference and the changes in corneal and ocular RMS of total HOAs and SA (r
      range: 0.281 to 0.492, P<0.05). Only the change of corneal coma RMS was
      correlated with midperipheral-central thickness change difference (r=0.270,
      P<0.05). The change in corneal horizontal coma was correlated with the temporal
      nasal thickness change difference (r=-0.289, P<0.05). CONCLUSIONS: Overnight OK
      caused unique changes in corneal thickness profiles at the vertical and
      horizontal meridians and increased corneal and ocular HOAs related to corneal
      reshaping.

PMID- 24681614
TI  - Precursor directed synthesis--"molecular" mechanisms in the Soft Chemistry
      approaches and their use for template-free synthesis of metal, metal oxide and
      metal chalcogenide nanoparticles and nanostructures.
AB  - This review provides an insight into the common reaction mechanisms in Soft
      Chemistry processes involved in nucleation, growth and aggregation of metal,
      metal oxide and chalcogenide nanoparticles starting from metal-organic precursors
      such as metal alkoxides, beta-diketonates, carboxylates and their chalcogene
      analogues and demonstrates how mastering the precursor chemistry permits us to
      control the chemical and phase composition, crystallinity, morphology, porosity
      and surface characteristics of produced nanomaterials. 

PMID- 24681613
TI  - The effect of room illumination on the measurement of anterior segment
      parameters.
AB  - OBJECTIVE: To evaluate the effect of room illumination on the measurement of
      anterior segment parameters. METHODS: In this comparative study, measurements of
      anterior segment parameters of 25 eyes of 25 healthy patients were performed by
      optical low-coherence reflectometry (OLCR). Measurements were taken under
      photopic conditions (150 lux) and under mesopic conditions (3 lux). Paired t test
      by SPSS 16.0 was used to compare the anterior segment measurements performed in
      both conditions. A P value lower than 0.05 was accepted as statistically
      significant. RESULTS: The mean age of the patients was 27.09+/-1.72 years (range,
      20-40 years). Of the anterior segment parameters, axial length and keratometry
      did not show significant difference between photopic and mesopic conditions
      (P=0.541 and P=0.812, respectively). The mean anterior chamber depth measurements
      was 3.04+/-0.35 mm and 3.06+/-0.35 mm, whereas the mean lens thickness was 3.75+/
      0.36 mm and 3.77+/-0.36 mm in the mesopic and photopic conditions, respectively.
      The mean pupil diameter measurement was 4.86+/-0.70 mm under photopic conditions
      and 6.36+/-0.94 mm under mesopic conditions. The anterior chamber depth, lens
      thickness, and pupil diameter showed significant difference between photopic and
      mesopic conditions (P=0.01, P=0.006, and P=0.0001, respectively). CONCLUSION:
      Anterior chamber depth, lens thickness, and pupil diameter were affected by the
      changes in luminance while performing measurements with OLCR. Considering the age
      of the study group, further studies are needed to test the measurement of
      accommodation amplitude.

PMID- 24681616
TI  - Translocations of chromosome end-segments and facultative heterochromatin promote
      meiotic ring formation in evening primroses.
AB  - Due to reciprocal chromosomal translocations, many species of Oenothera (evening
      primrose) form permanent multichromosomal meiotic rings. However, regular
      bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends,
      which makes homologous recombination virtually undetectable. Genetic diversity is
      achieved by changing linkage relations of chromosomes in rings and bivalents via
      hybridization and reciprocal translocations. Although the structural prerequisite
      for this system is enigmatic, whole-arm translocations are widely assumed to be
      the mechanistic driving force. We demonstrate that this prerequisite is genome
      compartmentation into two epigenetically defined chromatin fractions. The first
      one facultatively condenses in cycling cells into chromocenters negative both for
      histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed
      middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in
      differentiating cells. The second fraction is euchromatin confined to distal
      chromosome segments, positive for histone H3 lysine 4 dimethylation and for
      histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical
      telomeres but capped with constitutive heterochromatin. This genomic organization
      promotes translocation breakpoints between the two chromatin fractions, thus
      facilitating exchanges of end-segments. We challenge the whole-arm translocation
      hypothesis by demonstrating why reciprocal translocations of chromosomal end
      segments should strongly promote meiotic rings and evolution toward permanent
      translocation heterozygosity. Reshuffled end-segments, each possessing a major
      crossover hot spot, can furthermore explain meiotic compatibility between genomes
      with different translocation histories. 

PMID- 24681615
TI  - POLYGALACTURONASE INVOLVED IN EXPANSION1 functions in cell elongation and flower
      development in Arabidopsis.
AB  - Pectins are acidic carbohydrates that comprise a significant fraction of the
      primary walls of eudicotyledonous plant cells. They influence wall porosity and
      extensibility, thus controlling cell and organ growth during plant development.
      The regulated degradation of pectins is required for many cell separation events
      in plants, but the role of pectin degradation in cell expansion is poorly
      defined. Using an activation tag screen designed to isolate genes involved in
      wall expansion, we identified a gene encoding a putative polygalacturonase that,
      when overexpressed, resulted in enhanced hypocotyl elongation in etiolated
      Arabidopsis thaliana seedlings. We named this gene POLYGALACTURONASE INVOLVED IN
      EXPANSION1 (PGX1). Plants lacking PGX1 display reduced hypocotyl elongation that
      is complemented by transgenic PGX1 expression. PGX1 is expressed in expanding
      tissues throughout development, including seedlings, roots, leaves, and flowers.
      PGX1-GFP (green fluorescent protein) localizes to the apoplast, and
      heterologously expressed PGX1 displays in vitro polygalacturonase activity,
      supporting a function for this protein in apoplastic pectin degradation. Plants
      either overexpressing or lacking PGX1 display alterations in total
      polygalacturonase activity, pectin molecular mass, and wall composition and also
      display higher proportions of flowers with extra petals, suggesting PGX1's
      involvement in floral organ patterning. These results reveal new roles for
      polygalacturonases in plant development. 

PMID- 24681617
TI  - A cyanobacterial chlorophyll synthase-HliD complex associates with the Ycf39
      protein and the YidC/Alb3 insertase.
AB  - Macromolecular membrane assemblies of chlorophyll-protein complexes efficiently
      harvest and trap light energy for photosynthesis. To investigate the delivery of
      chlorophylls to the newly synthesized photosystem apoproteins, a terminal enzyme
      of chlorophyll biosynthesis, chlorophyll synthase (ChlG), was tagged in the
      cyanobacterium Synechocystis PCC 6803 (Synechocystis) and used as bait in pull
      down experiments. We retrieved an enzymatically active complex comprising ChlG
      and the high-light-inducible protein HliD, which associates with the Ycf39
      protein, a putative assembly factor for photosystem II, and with the YidC/Alb3
      insertase. 2D electrophoresis and immunoblotting also provided evidence for the
      presence of SecY and ribosome subunits. The isolated complex contained
      chlorophyll, chlorophyllide, and carotenoid pigments. Deletion of hliD elevated
      the level of the ChlG substrate, chlorophyllide, more than 6-fold; HliD is
      apparently required for assembly of FLAG-ChlG into larger complexes with other
      proteins such as Ycf39. These data reveal a link between chlorophyll biosynthesis
      and the Sec/YidC-dependent cotranslational insertion of nascent photosystem
      polypeptides into membranes. We expect that this close physical linkage
      coordinates the arrival of pigments and nascent apoproteins to produce
      photosynthetic pigment-protein complexes with minimal risk of accumulating
      phototoxic unbound chlorophylls. 

PMID- 24681618
TI  - Evolutionary origins of a bioactive peptide buried within Preproalbumin.
AB  - The de novo evolution of proteins is now considered a frequented route for
      biological innovation, but the genetic and biochemical processes that lead to
      each newly created protein are often poorly documented. The common sunflower
      (Helianthus annuus) contains the unusual gene PawS1 (Preproalbumin with SFTI-1)
      that encodes a precursor for seed storage albumin; however, in a region usually
      discarded during albumin maturation, its sequence is matured into SFTI-1, a
      protease-inhibiting cyclic peptide with a motif homologous to unrelated
      inhibitors from legumes, cereals, and frogs. To understand how PawS1 acquired
      this additional peptide with novel biochemical functionality, we cloned PawS1
      genes and showed that this dual destiny is over 18 million years old. This new
      family of mostly backbone-cyclic peptides is structurally diverse, but the
      protease-inhibitory motif was restricted to peptides from sunflower and close
      relatives from its subtribe. We describe a widely distributed, potential
      evolutionary intermediate PawS-Like1 (PawL1), which is matured into storage
      albumin, but makes no stable peptide despite possessing residues essential for
      processing and cyclization from within PawS1. Using sequences we cloned, we
      retrodict the likely stepwise creation of PawS1's additional destiny within a
      simple albumin precursor. We propose that relaxed selection enabled SFTI-1 to
      evolve its inhibitor function by converging upon a successful sequence and
      structure. 

PMID- 24681619
TI  - The most deeply conserved noncoding sequences in plants serve similar functions
      to those in vertebrates despite large differences in evolutionary rates.
AB  - In vertebrates, conserved noncoding elements (CNEs) are functionally constrained
      sequences that can show striking conservation over >400 million years of
      evolutionary distance and frequently are located megabases away from target
      developmental genes. Conserved noncoding sequences (CNSs) in plants are much
      shorter, and it has been difficult to detect conservation among distantly related
      genomes. In this article, we show not only that CNS sequences can be detected
      throughout the eudicot clade of flowering plants, but also that a subset of 37
      CNSs can be found in all flowering plants (diverging ~170 million years ago).
      These CNSs are functionally similar to vertebrate CNEs, being highly associated
      with transcription factor and development genes and enriched in transcription
      factor binding sites. Some of the most highly conserved sequences occur in genes
      encoding RNA binding proteins, particularly the RNA splicing-associated SR genes.
      Differences in sequence conservation between plants and animals are likely to
      reflect differences in the biology of the organisms, with plants being much more
      able to tolerate genomic deletions and whole-genome duplication events due, in
      part, to their far greater fecundity compared with vertebrates. 

PMID- 24681620
TI  - Discovery of a chlorophyll binding protein complex involved in the early steps of
      photosystem II assembly in Synechocystis.
AB  - Efficient assembly and repair of the oxygen-evolving photosystem II (PSII)
      complex is vital for maintaining photosynthetic activity in plants, algae, and
      cyanobacteria. How chlorophyll is delivered to PSII during assembly and how
      vulnerable assembly complexes are protected from photodamage are unknown. Here,
      we identify a chlorophyll and beta-carotene binding protein complex in the
      cyanobacterium Synechocystis PCC 6803 important for formation of the D1/D2
      reaction center assembly complex. It is composed of putative short-chain
      dehydrogenase/reductase Ycf39, encoded by the slr0399 gene, and two members of
      the high-light-inducible protein (Hlip) family, HliC and HliD, which are small
      membrane proteins related to the light-harvesting chlorophyll binding complexes
      found in plants. Perturbed chlorophyll recycling in a Ycf39-null mutant and
      copurification of chlorophyll synthase and unassembled D1 with the Ycf39-Hlip
      complex indicate a role in the delivery of chlorophyll to newly synthesized D1.
      Sequence similarities suggest the presence of a related complex in chloroplasts. 

PMID- 24681621
TI  - Characterization and evolution of tetrameric photosystem I from the thermophilic
      cyanobacterium Chroococcidiopsis sp TS-821.
AB  - Photosystem I (PSI) is a reaction center associated with oxygenic photosynthesis.
      Unlike the monomeric reaction centers in green and purple bacteria, PSI forms
      trimeric complexes in most cyanobacteria with a 3-fold rotational symmetry that
      is primarily stabilized via adjacent PsaL subunits; however, in plants/algae, PSI
      is monomeric. In this study, we discovered a tetrameric form of PSI in the
      thermophilic cyanobacterium Chroococcidiopsis sp TS-821 (TS-821). In TS-821, PSI
      forms tetrameric and dimeric species. We investigated these species by Blue
      Native PAGE, Suc density gradient centrifugation, 77K fluorescence, circular
      dichroism, and single-particle analysis. Transmission electron microscopy
      analysis of native membranes confirms the presence of the tetrameric PSI
      structure prior to detergent solubilization. To investigate why TS-821 forms
      tetramers instead of trimers, we cloned and analyzed its psaL gene.
      Interestingly, this gene product contains a short insert between the second and
      third predicted transmembrane helices. Phylogenetic analysis based on PsaL
      protein sequences shows that TS-821 is closely related to heterocyst-forming
      cyanobacteria, some of which also have a tetrameric form of PSI. These results
      are discussed in light of chloroplast evolution, and we propose that PSI evolved
      stepwise from a trimeric form to tetrameric oligomer en route to becoming
      monomeric in plants/algae. 

PMID- 24681623
TI  - Clinical implications of single- versus multiple-site keloid disorder: a
      retrospective study in an Asian population.
AB  - BACKGROUND: There is strong evidence of genetic susceptibility in individuals
      with keloid disorder. The purpose of this cross-sectional study was to determine
      the clinical relevance of our proposed variables on the multiplicity of keloids
      by further investigating the presence of other keloids and a family history.
      METHODS: This was a retrospective review, using institutional review board
      approved questionnaires, of patients with keloids who were seen at Kangbuk
      Samsung Hospital between December 2002 and February 2010. Eight hundred sixty
      eight patients were included in our study. Comparisons between the 2 groups were
      made using Mann-Whitney tests for continuous variables and chi2 tests for
      categorical variables. RESULTS: In our patient group, younger age of onset and
      the presence of family history were significantly associated with the occurrence
      of keloids at multiple sites. The locations of extra-auricular keloids, in order
      of frequency, included the shoulder; anterior chest, including the breasts;
      deltoid; trunk and pubic area; upper extremities; lower extremities; and other
      sites. As compared to secondary keloids, primary keloids were significantly
      associated with both a lower degree of recurrence and the presence of other
      keloids. The presence or absence of family history was significantly associated
      with the presence or absence of other keloids and primary or secondary keloids.
      CONCLUSIONS: Keloid disorder is one of the most frustrating problems in wound
      healing and advances in our understanding of the differences of occurrence at a
      single site versus multiple sites might help in understanding pathogenesis and
      improving treatment.

PMID- 24681622
TI  - Global dissection of alternative splicing in paleopolyploid soybean.
AB  - Alternative splicing (AS) is common in higher eukaryotes and plays an important
      role in gene posttranscriptional regulation. It has been suggested that AS varies
      dramatically among species, tissues, and duplicated gene families of different
      sizes. However, the genomic forces that govern AS variation remain poorly
      understood. Here, through genome-wide identification of AS events in the soybean
      (Glycine max) genome using high-throughput RNA sequencing of 28 samples from
      different developmental stages, we found that more than 63% of multiexonic genes
      underwent AS. More AS events occurred in the younger developmental stages than in
      the older developmental stages for the same type of tissue, and the four main AS
      types, exon skipping, intron retention, alternative donor sites, and alternative
      acceptor sites, exhibited different characteristics. Global computational
      analysis demonstrated that the variations of AS frequency and AS types were
      significantly correlated with the changes of gene features and gene
      transcriptional level. Further investigation suggested that the decrease of AS
      within the genome-wide duplicated genes were due to the diminution of intron
      length, exon number, and transcriptional level. Altogether, our study revealed
      that a large number of genes were alternatively spliced in the soybean genome and
      that variations in gene structure and transcriptional level may play important
      roles in regulating AS. 

PMID- 24681624
TI  - Preparation and evaluation of three mucoadhesive dosage forms using (99m)Tc
      Ofloxacin.
AB  - Preparation of three mucoadhesive formulations was optimized and pharmaceutically
      evaluated. Ofloxacin was radiolabeled with (99m)Tc and radiolabeled complex was
      characterized by HPLC. (99m)Tc-Ofloxacin was added as a tracer to the
      formulations namely Oflox C934, Oflox C940 and Oflox HPMC and the formulations
      were fed orally to rats. Imaging studies were carried out to assess the prolonged
      gastric retention of the formulations. (99m)Tc-Ofloxacin served as a good tracer
      for studying the pharmacokinetics of three controlled release mucoadhesive dosage
      forms by gamma scintigraphy studies. 

PMID- 24681626
TI  - Tracking contributions to human body burden of environmental chemicals by
      correlating environmental measurements with biomarkers.
AB  - The work addresses current knowledge gaps regarding causes for correlations
      between environmental and biomarker measurements and explores the
      underappreciated role of variability in disaggregating exposure attributes that
      contribute to biomarker levels. Our simulation-based study considers variability
      in environmental and food measurements, the relative contribution of various
      exposure sources (indoors and food), and the biological half-life of a compound,
      on the resulting correlations between biomarker and environmental measurements.
      For two hypothetical compounds whose half-lives are on the order of days for one
      and years for the other, we generate synthetic daily environmental concentrations
      and food exposures with different day-to-day and population variability as well
      as different amounts of home- and food-based exposure. Assuming that the total
      intake results only from home-based exposure and food ingestion, we estimate time
      dependent biomarker concentrations using a one-compartment pharmacokinetic model.
      Box plots of modeled R2 values indicate that although the R2 correlation between
      wipe and biological (e.g., serum) measurements is within the same range for the
      two compounds, the relative contribution of the home exposure to the total
      exposure could differ by up to 20%, thus providing the relative indication of
      their contribution to body burden. The novel method introduced in this paper
      provides insights for evaluating scenarios or experiments where sample, exposure,
      and compound variability must be weighed in order to interpret associations
      between exposure data. 

PMID- 24681625
TI  - HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2
      infected patients failing a raltegravir-containing regimen.
AB  - To characterize the HIV-2 integrase gene polymorphisms and the pathways to
      resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied
      63 integrase strand transfer inhibitors (INSTI)-naive patients, and 10 heavily
      pretreated patients exhibiting virological failure while receiving a salvage
      raltegravir-containing regimen. All patients were infected by HIV-2 group A.
      61.4% of the integrase residues were conserved, including the catalytic motif
      residues. No INSTI-major resistance mutations were detected in the virus
      population from naive patients, but two amino acids that are secondary resistance
      mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced
      patients exhibited resistance mutations via three main genetic pathways: N155H,
      Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10
      patients). Other mutations associated to raltegravir resistance in HIV-1 were
      also observed in our HIV-2 population (V151I and D232N), along with several novel
      mutations previously unreported. Data retrieved from this study should help build
      a more robust HIV-2-specific algorithm for the genotypic interpretation of
      raltegravir resistance, and contribute to improve the clinical monitoring of HIV
      2-infected patients. 

PMID- 24681627
TI  - A long QT mutation substitutes cholesterol for phosphatidylinositol-4,5
      bisphosphate in KCNQ1 channel regulation.
AB  - INTRODUCTION: Phosphatidylinositol-4,5-bisphosphate (PIP2) is a cofactor
      necessary for the activity of KCNQ1 channels. Some Long QT mutations of KCNQ1,
      including R243H, R539W and R555C have been shown to decrease KCNQ1 interaction
      with PIP2. A previous study suggested that R539W is paradoxically less sensitive
      to intracellular magnesium inhibition than the WT channel, despite a decreased
      interaction with PIP2. In the present study, we confirm this peculiar behavior of
      R539W and suggest a molecular mechanism underlying it. METHODS AND RESULTS: COS-7
      cells were transfected with WT or mutated KCNE1-KCNQ1 channel, and patch-clamp
      recordings were performed in giant-patch, permeabilized-patch or ruptured-patch
      configuration. Similar to other channels with a decreased PIP2 affinity, we
      observed that the R243H and R555C mutations lead to an accelerated current
      rundown when membrane PIP2 levels are decreasing. As opposed to R243H and R555C
      mutants, R539W is not more but rather less sensitive to PIP2 decrease than the WT
      channel. A molecular model of a fragment of the KCNQ1 C-terminus and the membrane
      bilayer suggested that a potential novel interaction of R539W with cholesterol
      stabilizes the channel opening and hence prevents rundown upon PIP2 depletion. We
      then carried out the same rundown experiments under cholesterol depletion and
      observed an accelerated R539W rundown that is consistent with this model.
      CONCLUSIONS: We show for the first time that a mutation may shift the channel
      interaction with PIP2 to a preference for cholesterol. This de novo interaction
      wanes the sensitivity to PIP2 variations, showing that a mutated channel with a
      decreased affinity to PIP2 could paradoxically present a slowed current rundown
      compared to the WT channel. This suggests that caution is required when using
      measurements of current rundown as an indicator to compare WT and mutant channel
      PIP2 sensitivity.

PMID- 24681629
TI  - Synthesis and anti-tuberculosis activity of the marine natural product caulerpin
      and its analogues.
AB  - Caulerpin (1a), a bis-indole alkaloid from the marine algal Caulerpa sp., was
      synthesized in three reaction steps with an overall yield of 11%. The caulerpin
      analogues (1b-1g) were prepared using the same synthetic pathway with overall
      yields between 3% and 8%. The key reaction involved a radical oxidative aromatic
      substitution involving xanthate (3) and 3-formylindole compounds (4a-4g). All bis
      indole compounds synthesized were evaluated against the Mycobacterium
      tuberculosis strain H37Rv, and 1a was found to display excellent activity (IC50
      0.24 uM).

PMID- 24681628
TI  - Inertial particle separation by differential equilibrium positions in a
      symmetrical serpentine micro-channel.
AB  - This paper presents an inertial microfluidic device with a simple serpentine
      micro-channel to continuously separate particles with high performance.
      Separation of micro/nano-particles has a variety of potential applications in
      biomedicine and industry. Among the existing separation technologies, a label
      free technique without the use of antibody affinity, filter or centrifugation is
      highly desired to ensure minimal damage and alteration to the cells. Inertial
      microfluidics utilising hydrodynamic forces to separate particles is one of the
      most suitable label-free technologies with a high throughput. Our separation
      concept relies on size-based differential equilibrium positions of the particles
      perpendicular to the flow. Highly efficient separation is demonstrated with
      particles of different sizes. The results indicate that the proposed device has
      an integrative advantage to the existing microfluidic separation techniques,
      taking accounts of purity, efficiency, parallelizability, footprint, throughput
      and resolution. Our device is expected to be a good alternative to conventional
      separation methods for sample preparation and clinical diagnosis. 

PMID- 24681630
TI  - Peridinin from the marine symbiotic dinoflagellate, Symbiodinium sp., regulates
      eosinophilia in mice.
AB  - Peridinin and fucoxanthin, which are natural carotenoids isolated from a
      symbiotic dinoflagellate, Symbiodinium sp., and a brown alga, Petalonia fascia,
      respectively, were compared for inhibitory effects on delayed-type
      hypersensitivity in mice. The number of eosinophils at the site of inflammation
      and in peripheral blood was compared for the administration of peridinin and
      fucoxanthin applied by painting and intraperitoneally. Peridinin, but not the
      structurally-related fucoxanthin, significantly suppressed the number of
      eosinophils in both the ear lobe and peripheral blood. Furthermore, peridinin
      applied topically, but not administered intraperitoneally, suppressed the level
      of eotaxin in the ears of sensitized mice. Fucoxanthin weakly suppressed the
      concentration of eotaxin in ears only by intraperitoneal administration. Although
      both carotenoids inhibited the migration of eosinophils toward eotaxin, the
      inhibitory effect of peridinin was higher than that of fucoxanthin. Peridinin may
      be a potential agent for suppressing allergic inflammatory responses, such as
      atopic dermatitis, in which eosinophils play a major role in the increase of
      inflammation. 

PMID- 24681632
TI  - New insight into chemical changes of dissolved organic matter during anaerobic
      digestion of dewatered sewage sludge using EEM-PARAFAC and two-dimensional FTIR
      correlation spectroscopy.
AB  - Dissolved organic matter (DOM) is a key component in reaction network of
      anaerobic digestion. In this study, fluorescent excitation-emission matrix
      parallel factor (EEM-PARAFAC) analysis and two-dimensional (2D) FTIR correlation
      spectroscopy were firstly used to explore chemical changes of soluble
      intermediates in high-solid biogas reactor. EEM-PARAFAC showed that fluorescent
      components (tyrosine-like, tryptophan-like and humic-like groups) in DOM over
      time increased gradually, implying that these groups were reluctant to biodegrade
      (acidogenesis). The resistance to biodegradation presented the following order:
      humic-like group>tyrosine-like group>tryptophan-like group. 2D FTIR correlation
      spectroscopy indicated that the DOM change sequence with time followed the order:
      protein-like groups>structural carbohydrates and carboxylic acids>polysaccharides
      like groups. Fluorescence intensities from EEM-PARAFAC and main bands of FTIR
      spectra correlated significantly with other chemical parameters, e.g. biogas
      production and dissolved organic carbon content. These findings supply novel
      realization for degradation degree and order of individual DOMs during anaerobic
      digestion for dewatered sewage sludge. 

PMID- 24681631
TI  - A practical strategy to discover new antitumor compounds by activating silent
      metabolite production in fungi by diethyl sulphate mutagenesis.
AB  - Many fungal biosynthetic pathways are silent in standard culture conditions, and
      activation of the silent pathways may enable access to new metabolites with
      antitumor activities. The aim of the present study was to develop a practical
      strategy for microbial chemists to access silent metabolites in fungi. We
      demonstrated this strategy using a marine-derived fungus Penicillium purpurogenum
      G59 and a modified diethyl sulphate mutagenesis procedure. Using this strategy,
      we discovered four new antitumor compounds named penicimutanolone (1),
      penicimutanin A (2), penicimutanin B (3), and penicimutatin (4). Structures of
      the new compounds were elucidated by spectroscopic methods, especially extensive
      2D NMR analysis. Antitumor activities were assayed by the MTT method using human
      cancer cell lines. Bioassays and HPLC-photodiode array detector (PDAD)-UV and
      HPLC-electron spray ionization (ESI)-MS analyses were used to estimate the
      activated secondary metabolite production. Compounds 2 and 3 had novel
      structures, and 1 was a new compound belonging to a class of very rare natural
      products from which only four members are so far known. Compounds 1-3 inhibited
      several human cancer cell lines with IC50 values lower than 20 MUM, and 4
      inhibited the cell lines to some extent. These results demonstrated the
      effectiveness of this strategy to discover new compounds by activating silent
      fungal metabolic pathways. These discoveries provide rationale for the increased
      use of chemical mutagenesis strategies in silent fungal metabolite studies.

PMID- 24681633
TI  - About supramolecular systems for dynamically probing cells.
AB  - This article reviews the state of the art in the development of strategies for
      generating supramolecular systems for dynamic cell studies. Dynamic systems are
      crucial to further our understanding of cell biology and are consequently at the
      heart of many medical applications. Increasing interest has therefore been
      focused recently on rendering systems bioactive and dynamic that can subsequently
      be employed to engage with cells. Different approaches using supramolecular
      chemistry are reviewed with particular emphasis on their application in cell
      studies. We conclude with an outlook on future challenges for dynamic cell
      research and applications. 

PMID- 24681634
TI  - Current methods in electrocardiogram characterization.
AB  - The Electrocardiogram (ECG) is the P-QRS-T wave depicting the cardiac activity of
      the heart. The subtle changes in the electric potential patterns of
      repolarization and depolarization are indicative of the disease afflicting the
      patient. These clinical time domain features of the ECG waveform can be used in
      cardiac health diagnosis. Due to the presence of noise and minute morphological
      parameter values, it is very difficult to identify the ECG classes accurately by
      the naked eye. Various computer aided cardiac diagnosis (CACD) systems, analysis
      methods, challenges addressed and the future of cardiovascular disease screening
      are reviewed in this paper. Methods developed for time domain, frequency
      transform domain, and time-frequency domain analysis, such as the wavelet
      transform, cannot by themselves represent the inherent distinguishing features
      accurately. Hence, nonlinear methods which can capture the small variations in
      the ECG signal and provide improved accuracy in the presence of noise are
      discussed in greater detail in this review. A CACD system exploiting these
      nonlinear features can help clinicians to diagnose cardiovascular disease more
      accurately. 

PMID- 24681635
TI  - [Evaluation of France's contributions to the Global Fund to Fight AIDS,
      Tuberculosis and Malaria: Ten years later].
AB  - For 30 years, France has been very committed politically in the international
      combat against AIDS. The discovery of the AIDS virus at the Pasteur Institute in
      1983, the AIDS summit meeting convened by Simone Veil in 1994, the excellence of
      research by French institutions on its virologic and other aspects as well as the
      socioeconomic and anthropological issues, and the strong commitment to
      international technical cooperation against this disease - all these have made
      (and continue to make) France a major political, technical, and financial
      participant in this battle against the combined pandemic of AIDS and
      tuberculosis. More than 10 years after the creation of the Global Fund, 5 years
      after the first evaluation of this Fund, and 2 years before the schedule for
      meeting the Millennium Development Goals, an assessment commissioned in 2013 from
      a French consulting firm of the French contributions is timely. The study was
      expected. Its results are disappointing. Why? Because the team chosen to conduct
      the assessment has a limited knowledge of the history of the interventions
      already funded by France and of the results of earlier assessments. The point was
      not to repeat the same observations but to move forward to see where they lead.
      In addition, the current and coming challenges are not considered. The countries
      to which France is providing cooperation are on the continent that after 30 years
      remains the most heavily affected by the pandemic. Several transitions are
      occurring there simultaneously: epidemiologic, demographic and urban. These
      metamorphoses influencing social values quite substantially, as well as risk
      factors for transmission of the AIDS virus; at the same time, they facilitate
      overcrowding and the propagation of tuberculosis. Nor do the authors consider the
      resistance of these infectious agents to the most commonly used drugs. The
      effects of the propagation of AIDS, of the expansion of armed conflicts in French
      speaking Africa and of the sexual violence alongside them are not mentioned,
      while France is intervening militarily in Mali! I use the observations of this
      assessment to discuss all these questions. 

PMID- 24681636
TI  - A cell-regulatory mechanism involving feedback between contraction and tissue
      formation guides wound healing progression.
AB  - Wound healing is a process driven by cells. The ability of cells to sense
      mechanical stimuli from the extracellular matrix that surrounds them is used to
      regulate the forces that cells exert on the tissue. Stresses exerted by cells
      play a central role in wound contraction and have been broadly modelled.
      Traditionally, these stresses are assumed to be dependent on variables such as
      the extracellular matrix and cell or collagen densities. However, we postulate
      that cells are able to regulate the healing process through a mechanosensing
      mechanism regulated by the contraction that they exert. We propose that cells
      adjust the contraction level to determine the tissue functions regulating all
      main activities, such as proliferation, differentiation and matrix production.
      Hence, a closed-regulatory feedback loop is proposed between contraction and
      tissue formation. The model consists of a system of partial differential
      equations that simulates the evolution of fibroblasts, myofibroblasts, collagen
      and a generic growth factor, as well as the deformation of the extracellular
      matrix. This model is able to predict the wound healing outcome without requiring
      the addition of phenomenological laws to describe the time-dependent contraction
      evolution. We have reproduced two in vivo experiments to evaluate the predictive
      capacity of the model, and we conclude that there is feedback between the level
      of cell contraction and the tissue regenerated in the wound. 

PMID- 24681639
TI  - Strain engineering of selective chemical adsorption on monolayer MoS2.
AB  - Nanomaterials are prone to influence by chemical adsorption because of their
      large surface to volume ratios. This enables sensitive detection of adsorbed
      chemical species which, in turn, can tune the properties of the host material.
      Recent studies discovered that single and multi-layer molybdenum disulfide (MoS2)
      films are ultra-sensitive to several important environmental molecules. Here we
      report new findings from ab inito calculations that reveal substantially enhanced
      adsorption of NO and NH3 on strained monolayer MoS2 with significant impact on
      the properties of the adsorbates and the MoS2 layer. The magnetic moment of
      adsorbed NO can be tuned between 0 and 1 MUB; strain also induces an electronic
      phase transition between the half-metal and the metal. Adsorption of NH3 weakens
      the MoS2 layer considerably, which explains the large discrepancy between the
      experimentally measured strength and breaking strain of MoS2 films and previous
      theoretical predictions. On the other hand, adsorption of NO2, CO, and CO2 is
      insensitive to the strain conditions in the MoS2 layer. This contrasting behavior
      allows sensitive strain engineering of selective chemical adsorption on MoS2 with
      effective tuning of mechanical, electronic, and magnetic properties. These
      results suggest new design strategies for constructing MoS2-based ultrahigh
      sensitivity nanoscale sensors and electromechanical devices. 

PMID- 24681637
TI  - Atg7- and Keap1-dependent autophagy protects breast cancer cell lines against
      mitoquinone-induced oxidative stress.
AB  - The interplay between oxidative stress and autophagy is critical for determining
      the fate of cancer cells exposed to redox-active and cytotoxic chemotherapeutic
      agents. Mitoquinone (MitoQ), a mitochondrially-targeted redox-active ubiquinone
      conjugate, selectively kills breast cancer cells over healthy mammary epithelial
      cells. We reported previously that MitoQ, although a derivative of the
      antioxidant ubiquinone, can generate excess ROS and trigger the Keap1-Nrf2
      antioxidant response in the MDA-MB-231 cell line. Following MitoQ treatment, a
      greater number of cells underwent autophagy than apoptosis. However, the
      relationship between MitoQ-induced oxidative stress and autophagy as a primary
      cellular response was unclear. In this report, we demonstrate that MitoQ induces
      autophagy related gene 7 (Atg7)-dependent, yet Beclin-1-independent, autophagy
      marked by an increase in LC3-II. Both the ATG7-deficient human MDA-MB-231 cells
      and Atg7-knockout mouse embryonic fibroblasts exhibited lower levels of autophagy
      following MitoQ treatment than their respective wild-type counterparts. Increased
      apoptosis was confirmed in these autophagy-deficient isogenic cell line pairs,
      indicating that autophagy was attempted for survival in wild type cell lines.
      Furthermore, we observed higher levels of ROS in Atg7-deficient cells, as
      measured by hydroethidine oxidation. In Atg7-deficient cells, redox-sensitive
      Keap1 degradation was decreased, suggesting autophagy- and Atg7-dependent
      degradation of Keap1. Conversely, downregulation of Keap1 decreased autophagy
      levels, increased Nrf2 activation, upregulated cytoprotective antioxidant gene
      expression, and caused accumulation of p62, suggesting a feedback loop between
      ROS-regulated Keap1-Nrf2 and Atg7-regulated autophagy. Our data indicate that
      excessive ROS causes the upregulation of autophagy, and autophagy acts as an
      antioxidant feedback response triggered by cytotoxic levels of MitoQ. 

PMID- 24681640
TI  - Common experiences of patients following suboptimal treatment outcomes:
      implications for epilepsy surgery.
AB  - Few studies have investigated the patient experience of unsuccessful medical
      interventions, particularly in the epilepsy surgery field. The present review
      aimed to gain insight into the patient experience of seizure recurrence after
      epilepsy surgery by examining the broader literature dealing with suboptimal
      results after medical interventions (including epilepsy surgery). To capture the
      patient experience, the literature search focused on qualitative research of
      patients who had undergone medically unsuccessful interventions, published in
      English in scholarly journals. Twenty-two studies were found of patients
      experiencing a range of suboptimal outcomes, including seizure recurrence, cancer
      recurrence and progression, unsuccessful joint replacement, unsuccessful
      infertility treatment, organ transplant rejection, coronary bypass graft surgery,
      and unsuccessful weight-loss surgery. In order of frequency, the most common
      patient experiences included the following: altered social dynamics and stigma,
      unmet expectations, negative emotions, use of coping strategies, hope and
      optimism, perceived failure of the treating team, psychiatric symptoms, and
      control issues. There is support in the epilepsy surgery literature that unmet
      expectations and psychiatric symptoms are key issues for patients with seizure
      recurrence, while other common patient experiences have been implied but not
      systematically examined. Several epilepsy surgery specific factors influence
      patient perceptions of seizure recurrence, including the nature of postoperative
      seizures, the presence of postoperative complications, and the need for increased
      postoperative medications. Knowledge of common patient experiences can assist in
      the delivery of patient follow-up and rehabilitation services tailored to
      differing outcomes after epilepsy surgery. 

PMID- 24681641
TI  - Adenosine A2A-receptor antagonist istradefylline enhances the motor response of L
      DOPA without worsening dyskinesia in MPTP-treated common marmosets.
AB  - The adenosine A2A-receptor antagonist istradefylline decreases OFF time in
      patients with Parkinson's disease who are already treated with optimal doses of
      dopaminergic medication but can cause an increase in non-troublesome dyskinesia.
      Preclinical experiments have shown that A2A antagonists are most effective in
      potentiating motor function when combined with sub-maximal doses of L-DOPA.
      However, the effects of combining istradefylline with sub-optimal L-DOPA
      treatment on established dyskinesia have not been studied. We now examine the
      effects of acute and repeated administration of istradefylline on dyskinesia in
      MPTP-treated common marmosets previously primed to exhibit involuntary movements
      by prior exposure to L-DOPA. In these animals, single dose acute oral
      administration of istradefylline (10 mg/kg) enhanced and prolonged the anti
      parkinsonian effects of a sub-optimal dose of L-DOPA (2.5 mg/kg). The chronic co
      administration of istradefylline (10 mg/kg) with L-DOPA (2.5 mg/kg) for 21 days
      did not worsen the severity of existing dyskinesia. Rather, the severity of
      dyskinesia tended to be reduced over the 21-day treatment period. These results
      suggest that istradefylline can be used to potentiate the effects of sub-optimal
      doses of L-DOPA in the treatment of Parkinson's disease without causing or
      worsening dyskinesia.

PMID- 24681642
TI  - Radiosynthesis and biological evaluation of N-[18F]labeled glutamic acid as a
      tumor metabolic imaging tracer.
AB  - We have previously reported that N-(2-[18F]fluoropropionyl)-L-methionine
      ([18F]FPMET) selectively accumulates in tumors. However, due to the poor
      pharmacokinetics of [18F]FPMET in vivo, the potential clinical translation of
      this observation is hampered. In this study, we rationally designed and
      synthesized [18F] or [11C]labeled N-position L-glutamic acid analogues for tumor
      imaging. N-(2-[18F]fluoropropionyl)-L-glutamic acid ([18F]FPGLU) was synthesized
      with a 30+/-10% (n = 10, decay-corrected) overall radiochemical yield and a
      specific activity of 40+/-25 GBq/MUmol (n = 10) after 130 min of radiosynthesis.
      In vitro cell experiments showed that [18F]FPGLU was primarily transported
      through the XAG(-) system and was not incorporated into protein. [18F]FPGLU was
      stable in urine, tumor tissues, and blood. We were able to use [18F]FPGLU in PET
      imaging and obtained high tumor to background ratios when visualizing tumors
      tissues in animal models.

PMID- 24681643
TI  - Minimally invasive foraminotomy through tubular retractors via a contralateral
      approach in patients with unilateral radiculopathy.
AB  - BACKGROUND: Radiculopathy caused by foraminal nerve root compression is a common
      pathology in the lumbar spine. Surgical decompression via a conventional open
      foraminotomy is the treatment of choice when surgery is indicated. Minimally
      invasive tubular foraminotomy through a contralateral approach is a potentially
      effective surgical alternative. OBJECTIVE: The aim of this retrospective cohort
      study was to evaluate the efficacy and benefits of this approach for treatment of
      radiculopathy. METHODS: Patients with unilaterally dominant lower extremity
      radiculopathy, who underwent minimally invasive lumbar foraminotomy through
      tubular retractors via a contralateral approach between 2010 and 2012, were
      included. Oswestry Disability Index (ODI) and the Visual Analogue Scale (VAS) for
      back and leg pain were evaluated preoperatively, postoperatively, and at the
      latest follow-up. Functional outcome was evaluated by using the MacNab criteria.
      RESULTS: For the total 32 patients, postoperatively there was significant
      improvement in the ODI (P = .006), VAS back pain (P < .001), and VAS leg pain on
      the pathology and the approach side (P = .004, P = .021, respectively). At follow
      up of 12.3 +/- 1.7 months, there was also significant improvement in the ODI (P <
      .001), VAS back pain (P = .001), and VAS leg pain on the pathology and the
      approach side (P < .001, P = .001, respectively). The functional outcome was
      excellent and good in 95.2%. One patient required fusion (3.1%). CONCLUSION: A
      minimally invasive, facet-sparing contralateral approach is an effective
      technique for treatment of radiculopathy due to foraminal compression. It also
      allows for decompression of lumbar spinal stenosis and bilateral lateral recess
      decompression without the need for fusion.

PMID- 24681644
TI  - Demystifying process mapping: a key step in neurosurgical quality improvement
      initiatives.
AB  - Reliable delivery of optimal care can be challenging for care providers. Health
      care leaders have integrated various business tools to assist them and their
      teams in ensuring consistent delivery of safe and top-quality care. The
      cornerstone to all quality improvement strategies is the detailed understanding
      of the current state of a process, captured by process mapping. Process mapping
      empowers caregivers to audit how they are currently delivering care to
      subsequently strategically plan improvement initiatives. As a community,
      neurosurgery has clearly shown dedication to enhancing patient safety and
      delivering quality care. A care redesign strategy named NERVS (Neurosurgery
      Enhanced Recovery after surgery, Value, and Safety) is currently being developed
      and piloted within our department. Through this initiative, a multidisciplinary
      team led by a clinician neurosurgeon has process mapped the way care is currently
      being delivered throughout the entire episode of care. Neurosurgeons are becoming
      leaders in quality programs, and their education on the quality improvement
      strategies and tools is essential. The authors present a comprehensive review of
      process mapping, demystifying its planning, its building, and its analysis. The
      particularities of using process maps, initially a business tool, in the health
      care arena are discussed, and their specific use in an academic neurosurgical
      department is presented.

PMID- 24681645
TI  - Thermoluminescence properties of the Cu-doped lithium potassium borate glass.
AB  - Characteristics of lithium potassium borate glasses with various copper
      concentrations are reported. The glasses were prepared by the melt quenching
      method and irradiated with photons to doses in the 0.5-4.0 Gy range. Glowing
      curves, dose response curves, reproducibility of the response, dose threshold,
      thermal fading and optical bleaching were studied.

PMID- 24681646
TI  - Pervasive nanoscale deformation twinning as a catalyst for efficient energy
      dissipation in a bioceramic armour.
AB  - Hierarchical composite materials design in biological exoskeletons achieves
      penetration resistance through a variety of energy-dissipating mechanisms while
      simultaneously balancing the need for damage localization to avoid compromising
      the mechanical integrity of the entire structure and to maintain multi-hit
      capability. Here, we show that the shell of the bivalve Placuna placenta (~99 wt%
      calcite), which possesses the unique optical property of ~80% total transmission
      of visible light, simultaneously achieves penetration resistance and deformation
      localization via increasing energy dissipation density (0.290 +/- 0.072 nJ MUm(
      3)) by approximately an order of magnitude relative to single-crystal geological
      calcite (0.034 +/- 0.013 nJ MUm(-3)). P. placenta, which is composed of a layered
      assembly of elongated diamond-shaped calcite crystals, undergoes pervasive
      nanoscale deformation twinning (width ~50 nm) surrounding the penetration zone,
      which catalyses a series of additional inelastic energy dissipating mechanisms
      such as interfacial and intracrystalline nanocracking, viscoplastic stretching of
      interfacial organic material, and nanograin formation and reorientation. 

PMID- 24681647
TI  - Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase
      inhibition.
AB  - Inhibitors of matrix metalloproteinases (MMPs) have been extensively explored to
      treat pathologies where excessive MMP activity contributes to adverse tissue
      remodelling. Although MMP inhibition remains a relevant therapeutic target, MMP
      inhibitors have not translated to clinical application owing to the dose-limiting
      side effects following systemic administration of the drugs. Here, we describe
      the synthesis of a polysaccharide-based hydrogel that can be locally injected
      into tissues and releases a recombinant tissue inhibitor of MMPs (rTIMP-3) in
      response to MMP activity. Specifically, rTIMP-3 is sequestered in the hydrogels
      through electrostatic interactions and is released as crosslinks are degraded by
      active MMPs. Targeted delivery of the hydrogel/rTIMP-3 construct to regions of
      MMP overexpression following a myocardial infarction significantly reduced MMP
      activity and attenuated adverse left ventricular remodelling in a porcine model
      of myocardial infarction. Our findings demonstrate that local, on-demand MMP
      inhibition is achievable through the use of an injectable and bioresponsive
      hydrogel. 

PMID- 24681648
TI  - Flammability properties of British heathland and moorland vegetation: models for
      predicting fire ignition.
AB  - Temperate ecosystems, for example British heathlands and moorlands, are predicted
      to experience an increase in severe summer drought and wildfire frequency over
      the next few decades. The development of fire ignition probability models is
      fundamental for developing fire-danger rating systems and predicting wildfire
      outbreaks. This work assessed the flammability properties of the fuel complex of
      British moorlands as a function of their moisture content under laboratory
      conditions. Specifically, we aimed to develop: (1) models of the probability of
      fire ignition in peat/litter fuel-beds (litter of four different plant species,
      Sphagnum moss and peat); (2) flammability properties in terms of ignitability,
      sustainability, consumability and combustibility of these peat/litter fuel-beds;
      (3) the probability of ignition in a canopy-layer of Calluna vulgaris (the most
      dominant heath/moor species in Britain) as a function of its dead-fuel proportion
      and moisture content; (4) the efficacy of standardized smouldering and flaming
      ignition sources in developing sustained ignitions. For this, a series of
      laboratory experiments simulating the fuel structure of moor vegetation were
      performed. The flammability properties in peat/litter fuel-beds were influenced
      strongly by the fuel moisture content. There were small differences in moisture
      thresholds for experiencing initial flaming ignitions (35-59%), however, the
      threshold for sustained ignitions (i.e. spreading a fixed distance from the
      ignition point) varied across a much wider range (19-55%). Litter/peat fuel-beds
      were classified into three groups: fuel-beds with high ignitability and
      combustibility, fuel-beds with high levels of sustainability, and fuel-beds with
      low levels in all flammability descriptors. The probability of ignition in the
      upper Calluna-vegetation layer was influenced by both the proportion of dead
      fuels and their moisture content, ranging from 19% to 35% of moisture as dead
      fuel proportion increased. Smouldering sources were more efficient in igniting
      peat/litter fuel-beds but in the Calluna-vegetation layer flaming sources
      performed better. This work can assist in improving the predictions of fire
      rating systems implemented in British moorlands, by providing better warnings
      based on critical moisture thresholds for various fuel types. 

PMID- 24681649
TI  - Groundwater pumping effects on contaminant loading management in agricultural
      regions.
AB  - Groundwater pumping changes the behavior of subsurface water, including the
      location of the water table and characteristics of the flow system, and
      eventually affects the fate of contaminants, such as nitrate from agricultural
      fertilizers. The objectives of this study were to demonstrate the importance of
      considering the existing pumping conditions for contaminant loading management
      and to develop a management model to obtain a contaminant loading design more
      appropriate and practical for agricultural regions where groundwater pumping is
      common. Results from this study found that optimal designs for contaminant
      loading could be determined differently when the existing pumping conditions were
      considered. This study also showed that prediction of contamination and
      contaminant loading management without considering pumping activities might be
      unrealistic. Motivated by these results, a management model optimizing the
      permissible on-ground contaminant loading mass together with pumping rates was
      developed and applied to field investigation and monitoring data from Icheon,
      Korea. The analytical solution for 1-D unsaturated solute transport was
      integrated with the 3-D saturated solute transport model in order to approximate
      the fate of contaminants loaded periodically from on-ground sources. This model
      was further expanded to manage agricultural contaminant loading in regions where
      groundwater extraction tends to be concentrated in a specific period of time,
      such as during the rice-growing season, using a method that approximates
      contaminant leaching to a fluctuating water table. The results illustrated that
      the simultaneous management of groundwater quantity and quality was effective and
      appropriate to the agricultural contaminant loading management and the model
      developed in this study, which can consider time-variant pumping, could be used
      to accurately estimate and to reasonably manage contaminant loading in
      agricultural areas. 

PMID- 24681650
TI  - Changes within a single land-use category alter microbial diversity and community
      structure: molecular evidence from wood-inhabiting fungi in forest ecosystems.
AB  - The impact of changes within a single land-use category or land-use intensity on
      microbial communities is poorly understood, especially with respect to fungi.
      Here we assessed how forest management regimes and a change in forest type affect
      the richness and community structure of wood-inhabiting fungi across Germany. We
      used molecular methods based on the length polymorphism of the internal
      transcribed spacers and the 5.8S rRNA gene to assess fungal operational taxonomic
      units (OTUs). A cloning/sequencing approach was used to identify taxonomic
      affinities of the fungal OTUs. Overall, 20-24% and 25-27% of native fungal OTUs
      from forest reserves and semi-natural forests became undetectable or were lost in
      managed and converted forests, respectively. Fungal richness was significantly
      reduced during a regeneration phase in age-class beech forests with a high level
      of wood extraction (P = 0.017), whereas fungal community structures were not
      significantly affected. Conversion of forests from native, deciduous to
      coniferous species caused significant changes in the fungal community structure
      (R = 0.64-0.66, P = 0.0001) and could reduce fungal richness (P < 0.05) which may
      depend on which coniferous species was introduced. Our results showed that
      Ascocoryne cylichnium, Armillaria sp., Exophiala moniliae, Hyphodontia
      subalutacea and Fomes fomentarius, all known for wood-decaying abilities were
      strongly reduced in their abundances when forests were converted from beech to
      coniferous. We conclude that changes within a single land-use category can be
      regarded as a major threat to fungal diversity in temperate forest ecosystems.

PMID- 24681651
TI  - Reconceptualizing 'effectiveness' in environmental projects: can we measure
      values-related achievements?
AB  - There have been recent calls for a shift to an evidence-based paradigm in
      environmental management, grounded in systematic monitoring and evaluation, but
      achieving this will be complex and difficult. Evaluating the educational
      components of environmental initiatives presents particular challenges, because
      these programs often have multiple concurrent goals and may value 'human
      outcomes', such as value change, which are intangible and difficult to quantify.
      This paper describes a fresh approach based on co-creating an entirely new values
      based assessment framework with expert practitioners worldwide. We first discuss
      the development of a generic framework of 'Proto-Indicators' (reference criteria
      constituting prototypes for measurable indicators), and then demonstrate its
      application within a reforestation project in Mexico where indicators and
      assessment tools were localized to enhance context-relevance. Rigorously derived
      using unitary validity, with an emphasis on relevance, practicability and logical
      consistency from user perspectives, this framework represents a step-wise advance
      in the evaluation of non-formal EE/ESD programs. This article also highlights
      three important principles with broader implications for evaluation, valuation
      and assessment processes within environmental management: namely peer
      elicitation, localizability, and an explicit focus on ethical values. We discuss
      these principles in relation to the development of sustainability indicators at
      local and global levels, especially in relation to post-2015 Sustainable
      Development Goals. 

PMID- 24681652
TI  - Motivations for rule compliance in support of forest health: replication and
      extension.
AB  - This study replicates and extends research conducted in 2008. Based on a random
      sample of 800 campers who used Wisconsin state parks and forests in 2010, it
      confirms that calculated, normative, and social motivations are all important
      determinants of firewood movement rule compliance, a context where regulatees
      have primarily sporadic short-term interests, and where costs of compliance and
      non-compliance are both low. The study uses bi-variate statistical tests and
      recursive partitioning (standard and conditional permutation random forests) for
      analysis, and discusses findings from the perspective of a natural resources
      regulator of activities in multiple domains (e.g., business and recreational uses
      of forests in both rural and urban settings). It demonstrates how knowledge of
      motivations for compliance can inform two integrative research and analysis
      frameworks - motivational postures and social marketing, and discusses how affect
      and social norms may be utilized to improve regulator effectiveness. 

PMID- 24681653
TI  - Microscopic colitis and colorectal neoplastic lesion rate in chronic nonbloody
      diarrhea: a prospective, multicenter study.
AB  - BACKGROUND: Lymphocytic and collagenous colitis are emerging as common findings
      in subjects undergoing colonoscopy for chronic non-bloody diarrhea (CNBD). Data
      concerning microscopic colitis (MC) are still limited and affected by
      controversial epidemiological evidences. Recent converging lines of evidence
      suggest that MC correlates a lower risk of colorectal neoplasia. Accordingly, we
      prospectively assessed MC prevalence in a multicenter cohort of subjects
      submitted to colonoscopy for CNBD, thereby defining whether MC influences the
      risk of colorectal neoplasia. METHODS: Consecutive patients with CNBD of unknown
      origin underwent pan-colonoscopy with multiple biopsies. The prevalence of
      neoplastic patients in MC was compared with that observed in negative CNBD
      subjects. RESULTS: Among 8006 colonoscopy, 305 subjects were enrolled for CNBD.
      Patients with CNBD were more likely to be women than men (odds ratio = 1.5; P =
      0.001). Histopathology detected high prevalence of MC (16%) with a clear
      predominance of collagenous colitis (70%). A striking age-dependent rise in MC
      associated risk was observed, depicting outstanding differences among varying age
      groups, as in the number needed to screen 1 new case. Gender distribution was
      balanced within MC patients (Female/Male = 1.5/1), especially among lymphocytic
      colitis (Female/Male = 1.2/1). MC patients were negatively associated with the
      risk of neoplastic polyps compared with negative CNBD subjects (odds ratio =
      0.22; P = 0.035). CONCLUSIONS: MC is the first cause of CNBD in subjects
      submitted to colonoscopy. Multiple biopsies are strongly recommended, even in the
      case of uneventful endoscopic inspection, especially for age >=40 years. MC has a
      reduced risk of colorectal neoplasia, suggesting that this model of chronic
      inflammation plays a protective effect against colorectal carcinogenesis.

PMID- 24681654
TI  - Vitamin D levels in adults with Crohn's disease are responsive to disease
      activity and treatment.
AB  - BACKGROUND: Vitamin D deficiency is common in patients with Crohn's disease (CD),
      although whether this impairs immune responsiveness, and is related to disease
      activity per se, remains unclear. We sought to investigate vitamin D pathways in
      patients with CD according to measures of inflammation and immune response.
      METHODS: Prospectively collected samples of a well-characterized cohort of
      patients with CD were used to measure serum 25(OH)-vitamin D levels by enzyme
      linked immunoassay. Related gene expression was determined by polymerase chain
      reaction in T cells. The effect of vitamin D on the proliferation of isolated CD4
      cells was determined. RESULTS: Patients with active CD had lower serum vitamin D
      levels than those in clinical remission; this measurement was independent of
      season or reported use of vitamin D supplements. Harvey-Bradshaw Index scores,
      but not C-reactive protein, correlated with serum vitamin D levels. Gene
      expression of the vitamin D receptor was higher in peripheral blood T cells from
      patients with active disease than in those in remission. The proportion of CD25hi
      CD4 cells from patients with CD increased in the presence of vitamin D. After
      treatment with infliximab, significant increases in serum vitamin D levels were
      noted in patients. CONCLUSIONS: Low vitamin D levels are associated with disease
      activity in CD and increase after infliximab treatment.

PMID- 24681656
TI  - Systematic review of cuff and pouch cancer in patients with ileal pelvic pouch
      for ulcerative colitis.
AB  - BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the procedure of choice for
      refractory or complicated ulcerative colitis (UC). Since 1990, pouch-related
      adenocarcinomas have been described. The aim of this study was to review the
      literature to evaluate the burden of this complication, seeking for risk factors,
      prevention, and ideal management. METHODS: We performed a systematic review of
      the literature to identify all described pouch-related adenocarcinoma in patients
      operated on with IPAA for UC. Studies were thoroughly evaluated to select
      authentic de novo pouch carcinomas. Some authors were contacted for additional
      information. Data of patients were pooled. Meta-analyses of suitable studies were
      attempted to identify risk factors. RESULTS: Thirty-four articles reported on 49
      patients (2:1, male:female) who developed unequivocal pouch-related
      adenocarcinoma, 14 (28.6%) and 33 (67.3%) arising from the pouch and anorectal
      mucosa, respectively. Origin was not reported in 2 (4%). Pooled cumulative
      incidence of pouch-related adenocarcinoma was 0.33% (95% confidence interval
      [CI], 0.31-0.34) 50 years after the diagnosis and 0.35% (95% CI, 0.34-0.36) 20
      years after IPAA. Primary pouch cancer incidence was below 0.02% 20 years after
      IPAA. Neoplasia on colectomy specimen was the strongest risk factor (odds ratio,
      8.8; 95% CI, 4.61-16.80). Mucosectomy did not abolish the risk of subsequent
      cancer but avoiding it increased 8 times the risk of cancer arising from the
      residual anorectal mucosa (odds ratio, 8; 95% CI, 1.3-48.7; P = 0.02).
      Surveillance is currently performed yearly starting 10 years since diagnosis, but
      cancers escaping this pathway are reported. In patients receiving mucosectomy, a
      5-year delay for surveillance could be proposed. CONCLUSIONS: Pouch-related
      adenocarcinomas are rare. Diagnosis of Crohn's disease in the long term may
      further decrease the rates in UC. Presumed evolution from dysplasia might offer a
      time window for cancer prevention. Abdominoperineal excision should be
      recommended for pouch-related adenocarcinomas.

PMID- 24681655
TI  - Genetic deletion of Klf4 in the mouse intestinal epithelium ameliorates dextran
      sodium sulfate-induced colitis by modulating the NF-kappaB pathway inflammatory
      response.
AB  - BACKGROUND: Kruppel-like factor 4 (KLF4) is a zinc finger transcription factor
      expressed in the differentiated epithelial cells lining of the intestine. Under
      physiological conditions, KLF4 inhibits cell proliferation. Conversely, KLF4
      mediates proinflammatory signaling in macrophages and its overexpression in the
      esophageal epithelium activates cytokines, leading to inflammation-mediated
      esophageal squamous cell cancer formation in mice. Here, we tested whether KLF4
      has a proinflammatory activity in experimental colitis in mice. METHODS: Villin
      Cre;Klf4 mice with intestine-specific Klf4 deletion (Klf4) and control mice with
      floxed Klf4 gene (Klf4) were treated or not with 3% dextran sodium sulfate (DSS)
      for 7 days to induce colitis. Additionally, WT mice were administered or not,
      nanoparticles loaded with scrambled or Klf4-siRNA, and concomitantly given DSS.
      RESULTS: Compared with DSS-treated Klf4 mice, DSS-treated Klf4 mice were
      significantly less sensitive to DSS-induced colitis. DSS treatment of Klf4 mice
      induced Klf4 expression in the crypt zone of the colonic epithelium. DSS-treated
      Klf4 mice had increased proliferation relative to DSS-treated control mice. DSS
      treatment induced NF-kappaB signaling pathway in Klf4 mice colon but not Klf4
      mice. Additionally, WT mice given DSS and nanoparticle/Klf4-siRNA were less
      sensitive to colitis and had reduced Klf4 expression and while maintaining the
      proliferative response in the colonic epithelium. CONCLUSIONS: Our results
      indicate that Klf4 is an important mediator of DSS-induced colonic inflammation
      by modulating NF-kappaB signaling pathway and could be involved in the
      pathogenesis and/or propagation of inflammatory bowel disease. Thus, Klf4 may
      represent a novel therapeutic target in inflammatory bowel disease.

PMID- 24681657
TI  - The risk of hypertension after preoperative discontinuation of angiotensin
      converting enzyme inhibitors or angiotensin receptor antagonists in ambulatory
      and same-day admission patients.
AB  - BACKGROUND: The continued use of angiotensin-converting enzyme inhibitors (ACEIs)
      and angiotensin II subtype I receptor antagonists (ARBs) medications in the
      preoperative period has been reported to be associated with intraoperative
      hypotension that can be unresponsive to pressor drugs. As a result, several
      investigators suggested discontinuation of these medications before scheduled
      surgery but did not report on unintended consequences that might result from
      discontinuation. We conducted a prospective, single-blind, randomized trial to
      observe the effect of the medications on preoperative arterial blood pressure
      recordings in patients presenting for ambulatory and same-day surgery. METHODS:
      Six hundred forty-four patients presenting for ambulatory and same-day surgery
      were enrolled prospectively between 2006 and 2011 and randomly assigned to 2
      groups based on continuation or discontinuation of ACEIs and ARBs. An intention
      to-treat analysis was performed. The primary outcome was presence of hypertension
      (HTN) immediately before surgery. Secondary outcomes included surgical
      cancellations due to HTN, prolongation of hospitalization, adverse clinical
      events, and HTN in the postoperative period. RESULTS: Data for 526 patients were
      analyzed. There were 262 patients in the discontinuation group and 264 patients
      in the continuation group. Discontinuation of ACEIs and ARBs on the day of
      surgery was not associated with increased prevalence of preoperative HTN (P =
      0.775). The upper bound of a 95% confidence interval for the difference in
      prevalence of Stage 1 and 2 HTN between study arms indicates that discontinuation
      of study medication is unlikely to be associated with an increase in Stage 1 HTN
      of >4.8 percentage points and in Stage 2 HTN of no >5.8 percentage points.
      Discontinuation was not associated with an increase in postoperative HTN, with
      prolongation of hospitalization or with adverse clinical events. CONCLUSIONS:
      Discontinuing ACEIs and ARBs in patients on the day of surgery did not result in
      a substantively increased incidence of pre- or postoperative HTN compared with
      patients who continued these medications on the day of surgery. The results
      provide an evidentiary basis for the safety of discontinuing ACEIs and ARBs on
      the day of surgery without increasing adverse hemodynamic outcomes.

PMID- 24681658
TI  - The incidence and prevention of hypothermia in newborn bonding after cesarean
      delivery: a randomized controlled trial.
AB  - BACKGROUND: Little is known about thermoregulation of the newborn while bonding
      on the mother's chest immediately after cesarean delivery. Newborn hypothermia is
      associated with serious complications and should be avoided. Therefore, we
      evaluated whether newborns develop hypothermia during intraoperative bonding
      while positioned on their mothers' chests and investigated the effects of active
      cutaneous warming of the mothers and babies during a 20-minute intraoperative
      bonding period. METHODS: We enrolled 40 parturients scheduled for elective
      cesarean delivery under spinal anesthesia. Mothers and their newborns were
      randomized to receive either passive insulation or forced-air skin-surface
      warming during the surgical procedure and bonding period. The primary outcome was
      neonatal core temperature at the end of the bonding period. Core temperatures of
      the newborns were measured with a rectal probe. Body temperatures of the mothers
      were assessed by sublingual measurements. Skin temperatures, thermal comfort of
      the mothers, and perioperative shivering were evaluated. RESULTS: Without active
      warming from the beginning of the surgical procedure until the end of the bonding
      period, the mean (SD) neonatal core temperature decreased to 35.9 (0.6) degrees
      C. Seventeen of 21 (81%) newborns became hypothermic (defined as a core
      temperature below 36.5 degrees C). Active skin-surface warming from the beginning
      of the surgical procedure until the end of the bonding period resulted in a
      neonatal core temperature of 37.0 (0.2) degrees C and a decreased incidence of
      hypothermia (1 of 19 (5%) newborns (P < 0.0001)). In addition, active warming
      increased the mean skin temperatures of the infants, maternal core and skin
      temperatures, maternal thermal comfort, and reduced perioperative shivering.
      CONCLUSIONS: Active forced-air warming of mothers and newborns immediately after
      cesarean delivery reduces the incidence of infant and maternal hypothermia and
      maternal shivering, and increases maternal comfort.

PMID- 24681659
TI  - Assessing the accuracy of common pediatric age-based weight estimation formulae.
AB  - BACKGROUND: Many of the common equations for weight estimation in children were
      either introduced before the widespread prevalence of childhood obesity or have
      not been assessed in overweight/obese children. Therefore, we assessed the
      accuracy of 3 common age-based weight estimation formulae (Advanced Pediatric
      Life Support, Luscombe, and Theron) for predicting the weight of children
      undergoing elective, noncardiac operations. We also developed and validated a new
      age-based weight estimation formula. METHODS: We used preoperative anthropometric
      and clinical data on 13,933 children aged 2 to 12 years to evaluate the
      performance of 3 pediatric age-based weight estimation formulae. Ability of the
      formulae to predict measured weights was assessed in a derivation cohort (75%
      randomly selected from the study sample). We also developed and validated a new
      age-based formula (the Michigan formula) that could be used to estimate the
      weight of contemporary American children. RESULTS: Among the 10,488 children in
      the derivation cohort, 31.8% were overweight or obese while 55.7% were boys. The
      accuracy of the formulae varied considerably. The Luscombe formula demonstrated
      the lowest mean bias of 3.4 kg (95% confidence interval, 3.2-3.5 kg) and 89.7% of
      estimates within 10% of measured weight. Our derived linear regression equation
      the "Michigan Formula" demonstrated the highest accuracy compared with the
      existing formulae with a bias of 4.6 kg (95% confidence interval, = 4.36-4.84 kg)
      and 92% of estimates within 10% of measured weights. CONCLUSIONS: Accuracies of
      current weight estimation formulae varied greatly. Our derived equation (Michigan
      formula: weight (kg) = 3 x age (yr) + 10) demonstrated high accuracy when
      compared with existing formulae and may be more applicable for estimating the
      weight of contemporary American children.

PMID- 24681660
TI  - A prospective comparison of a noninvasive cardiac output monitor versus
      esophageal Doppler monitor for goal-directed fluid therapy in colorectal surgery
      patients.
AB  - BACKGROUND: Goal-directed fluid therapy (GDFT) is associated with improved
      outcomes after surgery. The esophageal Doppler monitor (EDM) is widely used, but
      has several limitations. The NICOM, a completely noninvasive cardiac output
      monitor (Cheetah Medical), may be appropriate for guiding GDFT. No prospective
      studies have compared the NICOM and the EDM. We hypothesized that the NICOM is
      not significantly different from the EDM for monitoring during GDFT. METHODS: One
      hundred adult patients undergoing elective colorectal surgery participated in
      this study. Patients in phase I (n = 50) had intraoperative GDFT guided by the
      EDM while the NICOM was connected, and patients in phase II (n = 50) had
      intraoperative GDFT guided by the NICOM while the EDM was connected. Each
      patient's stroke volume was optimized using 250-mL colloid boluses. Agreement
      between the monitors was assessed, and patient outcomes (postoperative pain,
      nausea, and return of bowel function), complications (renal, pulmonary,
      infectious, and wound complications), and length of hospital stay (LOS) were
      compared. RESULTS: Using a 10% increase in stroke volume after fluid challenge,
      agreement between monitors was 60% at 5 minutes, 61% at 10 minutes, and 66% at 15
      minutes, with no significant systematic disagreement (McNemar P > 0.05) at any
      time point. The EDM had significantly more missing data than the NICOM. No
      clinically significant differences were found in total LOS or other outcomes. The
      mean LOS was 6.56 +/- 4.32 days in phase I and 6.07 +/- 2.85 days in phase II,
      and 95% confidence limits for the difference were -0.96 to +1.95 days (P =
      0.5016). CONCLUSIONS: The NICOM performs similarly to the EDM in guiding GDFT,
      with no clinically significant differences in outcomes, and offers increased ease
      of use as well as fewer missing data points. The NICOM may be a viable
      alternative monitor to guide GDFT.

PMID- 24681662
TI  - Recent developments of thiacalixarene based molecular motifs.
AB  - Thiacalixarenes, a subclass of "third generation" calixarenes, exhibit many
      interesting features such as enlarged ring size, facile chemical modification,
      and metal complexation due to the presence of bridging sulfur atoms. The
      thiacalixarene scaffold is a unique host with vast possibilities for
      functionalization not only at the upper and lower rim but also at the bridging
      sulfide groups. Modified thiacalixarenes have been used for many applications
      such as the detection and separation of biologically important cations, anions,
      and bio-analytes, mimicking molecular logic gates and devices, and synthesis of
      self-assembled coordination cages, multinuclear complexes, magnetic materials and
      luminescent materials. This review article summarizes recent developments in the
      derivatization methods of thiacalixarenes and their utilization in various
      applications. 

PMID- 24681661
TI  - Isolation of microplastics in biota-rich seawater samples and marine organisms.
AB  - Microplastic litter is a pervasive pollutant present in aquatic systems across
      the globe. A range of marine organisms have the capacity to ingest microplastics,
      resulting in adverse health effects. Developing methods to accurately quantify
      microplastics in productive marine waters, and those internalized by marine
      organisms, is of growing importance. Here we investigate the efficacy of using
      acid, alkaline and enzymatic digestion techniques in mineralizing biological
      material from marine surface trawls to reveal any microplastics present. Our
      optimized enzymatic protocol can digest >97% (by weight) of the material present
      in plankton-rich seawater samples without destroying any microplastic debris
      present. In applying the method to replicate marine samples from the western
      English Channel, we identified 0.27 microplastics m(-3). The protocol was further
      used to extract microplastics ingested by marine zooplankton under laboratory
      conditions. Our findings illustrate that enzymatic digestion can aid the
      detection of microplastic debris within seawater samples and marine biota. 

PMID- 24681664
TI  - Non-invasive assessment of Alzheimer's disease neurofibrillary pathology using
      18F-THK5105 PET.
AB  - Non-invasive imaging of tau pathology in the living brain would be useful for
      accurately diagnosing Alzheimer's disease, tracking disease progression, and
      evaluating the treatment efficacy of disease-specific therapeutics. In this
      study, we evaluated the clinical usefulness of a novel tau-imaging positron
      emission tomography tracer 18F-THK5105 in 16 human subjects including eight
      patients with Alzheimer's disease (three male and five females, 66-82 years) and
      eight healthy elderly controls (three male and five females, 63-76 years). All
      participants underwent neuropsychological examination and 3D magnetic resonance
      imaging, as well as both 18F-THK5105 and 11C-Pittsburgh compound B positron
      emission tomography scans. Standard uptake value ratios at 90-100 min and 40-70
      min post-injection were calculated for 18F-THK5105 and 11C-Pittsburgh compound B,
      respectively, using the cerebellar cortex as the reference region. As a result,
      significantly higher 18F-THK5105 retention was observed in the temporal,
      parietal, posterior cingulate, frontal and mesial temporal cortices of patients
      with Alzheimer's disease compared with healthy control subjects. In patients with
      Alzheimer's disease, the inferior temporal cortex, which is an area known to
      contain high densities of neurofibrillary tangles in the Alzheimer's disease
      brain, showed prominent 18F-THK5105 retention. Compared with high frequency
      (100%) of 18F-THK5105 retention in the temporal cortex of patients with
      Alzheimer's disease, frontal 18F-THK5105 retention was less frequent (37.5%) and
      was only observed in cases with moderate-to-severe Alzheimer's disease. In
      contrast, 11C-Pittsburgh compound B retention was highest in the posterior
      cingulate cortex, followed by the ventrolateral prefrontal, anterior cingulate,
      and superior temporal cortices, and did not correlate with 18F-THK5105 retention
      in the neocortex. In healthy control subjects, 18F-THK5105 retention was ~10%
      higher in the mesial temporal cortex than in the neocortex. Notably, unlike 11C
      Pittsburgh compound B, 18F-THK5105 retention was significantly correlated with
      cognitive parameters, hippocampal and whole brain grey matter volumes, which was
      consistent with findings from previous post-mortem studies showing significant
      correlations of neurofibrillary tangle density with dementia severity or neuronal
      loss. From these results, 18F-THK5105 positron emission tomography is considered
      to be useful for the non-invasive assessment of tau pathology in the living
      brain. This technique would be applicable to the longitudinal evaluation of tau
      deposition and allow a better understanding of the pathophysiology of Alzheimer's
      disease.

PMID- 24681663
TI  - Polyethylene glycol-coupled IGF1 delays motor function defects in a mouse model
      of spinal muscular atrophy with respiratory distress type 1.
AB  - Spinal muscular atrophy with respiratory distress type 1 is a neuromuscular
      disorder characterized by progressive weakness and atrophy of the diaphragm and
      skeletal muscles, leading to death in childhood. No effective treatment is
      available. The neuromuscular degeneration (Nmd(2J)) mouse shares a crucial
      mutation in the immunoglobulin mu-binding protein 2 gene (Ighmbp2) with spinal
      muscular atrophy with respiratory distress type 1 patients and also displays some
      basic features of the human disease. This model serves as a promising tool in
      understanding the complex mechanisms of the disease and in exploring novel
      treatment modalities such as insulin-like growth factor 1 (IGF1) which supports
      myogenic and neurogenic survival and stimulates differentiation during
      development. Here we investigated the treatment effects with polyethylene glycol
      coupled IGF1 and its mechanisms of action in neurons and muscles. Polyethylene
      glycol-coupled IGF1 was applied subcutaneously every second day from post-natal
      Day 14 to post-natal Day 42 and the outcome was assessed by morphology,
      electromyography, and molecular studies. We found reduced IGF1 serum levels in
      Nmd(2J) mice 2 weeks after birth, which was normalized by polyethylene glycol
      coupled IGF1 treatment. Nmd(2J) mice showed marked neurogenic muscle fibre
      atrophy in the gastrocnemius muscle and polyethylene glycol-coupled IGF1
      treatment resulted in muscle fibre hypertrophy and slowed fibre degeneration
      along with significantly higher numbers of functionally active axonal sprouts. In
      the diaphragm with predominant myogenic changes a profound protection from muscle
      fibre degeneration was observed under treatment. No effects of polyethylene
      glycol-coupled IGF1 were monitored at the level of motor neuron survival. The
      beneficial effects of polyethylene glycol-coupled IGF1 corresponded to a marked
      activation of the IGF1 receptor, resulting in enhanced phosphorylation of Akt
      (protein kinase B) and the ribosomal protein S6 kinase in striated muscles and
      spinal cord from Nmd(2J) mice. Based on these findings, polyethylene glycol
      coupled IGF1 may hold promise as a candidate for future treatment trials in human
      patients with spinal muscular atrophy with respiratory distress type 1. 

PMID- 24681665
TI  - Embedding quantum into classical: contextualization vs conditionalization.
AB  - We compare two approaches to embedding joint distributions of random variables
      recorded under different conditions (such as spins of entangled particles for
      different settings) into the framework of classical, Kolmogorovian probability
      theory. In the contextualization approach each random variable is "automatically"
      labeled by all conditions under which it is recorded, and the random variables
      across a set of mutually exclusive conditions are probabilistically coupled
      (imposed a joint distribution upon). Analysis of all possible probabilistic
      couplings for a given set of random variables allows one to characterize various
      relations between their separate distributions (such as Bell-type inequalities or
      quantum-mechanical constraints). In the conditionalization approach one considers
      the conditions under which the random variables are recorded as if they were
      values of another random variable, so that the observed distributions are
      interpreted as conditional ones. This approach is uninformative with respect to
      relations between the distributions observed under different conditions because
      any set of such distributions is compatible with any distribution assigned to the
      conditions. 

PMID- 24681667
TI  - Reduced graphene oxides: the thinnest and most lightweight materials with highly
      efficient microwave attenuation performances of the carbon world.
AB  - In this work, reduced graphene oxide (r-GO) and graphite nanosheet (GN) were
      obtained via the chemical approach. Furthermore, r-GO composites and GN
      composites were prepared with a paraffin wax host. r-GO composites show high
      dielectric properties and electromagnetic interference shielding efficiency (EMI
      SE). Compared with the GN composites, the loss tangent and EMI SE of the r-GO
      composites with the same mass ratio are enhanced ~5 to 10 times and ~3 to 10
      times, respectively. The enhanced attenuation capacity arises from higher
      specific surface area, clustered defects and residual bonds of the r-GOs, which
      increase the polarization loss, scattering and conductivity of the composite.
      Moreover, the higher conductivity of r-GO composites leads to higher EMI SE
      compared with that of GN composites. These results suggest that r-GOs are highly
      promising fillers for microwave attenuation in the carbon family and that r-GO
      composites are high-performance EMI shielding materials with application
      anticipated to many fields. 

PMID- 24681666
TI  - The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of
      cancer cell movement in mesenchymal and amoeboid migration style.
AB  - The receptor for the urokinase plasminogen activator (uPAR) is up-regulated in
      malignant tumors. Historically the function of uPAR in cancer cell invasion is
      strictly related to its property to promote uPA-dependent proteolysis of
      extracellular matrix and to open a path to malignant cells. These features are
      typical of mesenchymal motility. Here we show that the full-length form of uPAR
      is required when prostate and melanoma cancer cells convert their migration style
      from the "path generating" mesenchymal to the "path finding" amoeboid one, thus
      conferring a plasticity to tumor cell invasiveness across three-dimensional
      matrices. Indeed, in response to a protease inhibitors-rich milieu, prostate and
      melanoma cells activated an amoeboid invasion program connoted by retraction of
      cell protrusions, RhoA-mediated rounding of the cell body, formation of a
      cortical ring of actin and a reduction of Rac-1 activation. While the mesenchymal
      movement was reduced upon silencing of uPAR expression, the amoeboid one was
      almost completely abolished, in parallel with a deregulation of small Rho-GTPases
      activity. In melanoma and prostate cancer cells we have shown uPAR colocalization
      with beta1/beta3 integrins and actin cytoskeleton, as well integrins-actin co
      localization under both mesenchymal and amoeboid conditions. Such co
      localizations were lost upon treatment of cells with a peptide that inhibits uPAR
      integrin interactions. Similarly to uPAR silencing, the peptide reduced
      mesenchymal invasion and almost abolished the amoeboid one. These results
      indicate that full-length uPAR bridges the mesenchymal and amoeboid style of
      movement by an inward-oriented activity based on its property to promote integrin
      actin interactions and the following cytoskeleton assembly. 

PMID- 24681668
TI  - A novel approach to ECG classification based upon two-layered HMMs in body sensor
      networks.
AB  - This paper presents a novel approach to ECG signal filtering and classification.
      Unlike the traditional techniques which aim at collecting and processing the ECG
      signals with the patient being still, lying in bed in hospitals, our proposed
      algorithm is intentionally designed for monitoring and classifying the patient's
      ECG signals in the free-living environment. The patients are equipped with
      wearable ambulatory devices the whole day, which facilitates the real-time heart
      attack detection. In ECG preprocessing, an integral-coefficient-band-stop (ICBS)
      filter is applied, which omits time-consuming floating-point computations. In
      addition, two-layered Hidden Markov Models (HMMs) are applied to achieve ECG
      feature extraction and classification. The periodic ECG waveforms are segmented
      into ISO intervals, P subwave, QRS complex and T subwave respectively in the
      first HMM layer where expert-annotation assisted Baum-Welch algorithm is utilized
      in HMM modeling. Then the corresponding interval features are selected and
      applied to categorize the ECG into normal type or abnormal type (PVC, APC) in the
      second HMM layer. For verifying the effectiveness of our algorithm on abnormal
      signal detection, we have developed an ECG body sensor network (BSN) platform,
      whereby real-time ECG signals are collected, transmitted, displayed and the
      corresponding classification outcomes are deduced and shown on the BSN screen. 

PMID- 24681669
TI  - A novel teaching system for industrial robots.
AB  - The most important tool for controlling an industrial robotic arm is a teach
      pendant, which controls the robotic arm movement in work spaces and accomplishes
      teaching tasks. A good teaching tool should be easy to operate and can complete
      teaching tasks rapidly and effortlessly. In this study, a new teaching system is
      proposed for enabling users to operate robotic arms and accomplish teaching tasks
      easily. The proposed teaching system consists of the teach pen, optical markers
      on the pen, a motion capture system, and the pen tip estimation algorithm. With
      the marker positions captured by the motion capture system, the pose of the teach
      pen is accurately calculated by the pen tip algorithm and used to control the
      robot tool frame. In addition, Fitts' Law is adopted to verify the usefulness of
      this new system, and the results show that the system provides high accuracy,
      excellent operation performance, and a stable error rate. In addition, the system
      maintains superior performance, even when users work on platforms with different
      inclination angles. 

PMID- 24681670
TI  - Fruit detectability analysis for different camera positions in sweet-pepper.
AB  - For robotic harvesting of sweet-pepper fruits in greenhouses a sensor system is
      required to detect and localize the fruits on the plants. Due to the complex
      structure of the plant, most fruits are (partially) occluded when an image is
      taken from one viewpoint only. In this research the effect of multiple camera
      positions and viewing angles on fruit visibility and detectability was
      investigated. A recording device was built which allowed to place the camera
      under different azimuth and zenith angles and to move the camera horizontally
      along the crop row. Fourteen camera positions were chosen and the fruit
      visibility in the recorded images was manually determined for each position. For
      images taken from one position only with the criterion of maximum 50% occlusion
      per fruit, the fruit detectability (FD) was in no case higher than 69%. The best
      single positions were the front views and looking with a zenith angle of 60
      degrees  upwards. The FD increased when a combination was made of multiple
      viewpoint positions. With a combination of five favourite positions the maximum
      FD was 90%. 

PMID- 24681671
TI  - Ambient intelligence application based on environmental measurements performed
      with an assistant mobile robot.
AB  - This paper proposes the use of an autonomous assistant mobile robot in order to
      monitor the environmental conditions of a large indoor area and develop an
      ambient intelligence application. The mobile robot uses single high performance
      embedded sensors in order to collect and geo-reference environmental information
      such as ambient temperature, air velocity and orientation and gas concentration.
      The data collected with the assistant mobile robot is analyzed in order to detect
      unusual measurements or discrepancies and develop focused corrective ambient
      actions. This paper shows an example of the measurements performed in a research
      facility which have enabled the detection and location of an uncomfortable
      temperature profile inside an office of the research facility. The ambient
      intelligent application has been developed by performing some localized ambient
      measurements that have been analyzed in order to propose some ambient actuations
      to correct the uncomfortable temperature profile. 

PMID- 24681672
TI  - Electroless deposition and nanolithography can control the formation of materials
      at the nano-scale for plasmonic applications.
AB  - The new revolution in materials science is being driven by our ability to
      manipulate matter at the molecular level to create structures with novel
      functions and properties. The aim of this paper is to explore new strategies to
      obtain plasmonic metal nanostructures through the combination of a top down
      method, that is electron beam lithography, and a bottom up technique, that is the
      chemical electroless deposition. This technique allows a tight control over the
      shape and size of bi- and three-dimensional metal patterns at the nano scale. The
      resulting nanostructures can be used as constituents of Surface Enhanced Raman
      Spectroscopy (SERS) substrates, where the electromagnetic field is strongly
      amplified. Our results indicate that, in electroless growth, high quality metal
      nanostructures with sizes below 50 nm may be easily obtained. These findings were
      explained within the framework of a diffusion limited aggregation (DLA) model,
      that is a simulation model that makes it possible to decipher, at an atomic
      level, the rules governing the evolution of the growth front; moreover, we give a
      description of the physical mechanisms of growth at a basic level. In the
      discussion, we show how these findings can be utilized to fabricate dimers of
      silver nanospheres where the size and shape of those spheres is controlled with
      extreme precision and can be used for very large area SERS substrates and nano
      optics, for single molecule detection. 

PMID- 24681673
TI  - Oxygen sensing for industrial safety - evolution and new approaches.
AB  - The requirement for the detection of oxygen in industrial safety applications has
      historically been met by electrochemical technologies based on the consumption of
      metal anodes. Products using this approach have been technically and commercially
      successful for more than three decades. However, a combination of new
      requirements is driving the development of alternative approaches offering fresh
      opportunities and challenges. This paper reviews some key aspects in the
      evolution of consumable anode products and highlights recent developments in
      alternative technologies aimed at meeting current and anticipated future needs in
      this important application. 

PMID- 24681674
TI  - A pseudolite-based positioning system for legacy GNSS receivers.
AB  - The ephemeris data format of legacy GPS receivers is improper for positioning
      stationary pseudolites on the ground. Therefore, to utilize pseudolites for
      navigation, GPS receivers must be modified so that they can handle the modified
      data formats of the pseudolites. Because of this problem, the practical use of
      pseudolites has so far been limited. This paper proposes a pseudolite-based
      positioning system that can be used with unmodified legacy GPS receivers. In the
      proposed system, pseudolites transmit simulated GPS signals. The signals use
      standard GPS ephemeris data format and contain ephemeris data of simulated GPS
      satellites, not those of pseudolites. The use of the standard format enables the
      GPS receiver to process pseudolite signals without any modification. However, the
      position output of the GPS receiver is not the correct position in this system,
      because there are additional signal delays from each pseudolite to the receiver.
      A post-calculation process was added to obtain the correct receiver position
      using GPS receiver output. This re-estimation is possible because it is based on
      known information about the simulated signals, pseudolites, and positioning
      process of the GPS receiver. Simulations using generated data and live GPS data
      are conducted for various geometries to verify the proposed system. The test
      results show that the proposed system provides the desired user position using
      pseudolite signals without requiring any modifications to the legacy GPS
      receiver. In this initial study, a pseudolite-only indoor system was assumed.
      However, it can be expanded to a GPS-pseudolite system outdoors. 

PMID- 24681675
TI  - [The role of endoscopic ultrasound in the diagnosis and therapy of
      gastrointestinal disorders].
AB  - Endoscopic ultrasound is one of those diagnostic methods in gastrointestinal
      endoscopy which has developed rapidly in the last decade and has became
      exceedingly available to visualize the walls of the internal organs in details
      corresponding to histological layers, or analyze the adjacent structures. Fine
      needles and other endoscopic accessories can be introduced into the neighbouring
      tissues under the guidance of endoscopic ultrasound, and diagnostic and minimally
      invasive therapeutic interventions can be performed. The endoscopic ultrasound
      became more widely available in Hungary in recent years. This review focuses on
      the indications, benefits and complications of diagnostic and therapeutic
      endoscopic ultrasound. We recommend this article to gastroenterologists,
      surgeons, internists, pulmonologists, and to specialists in oncology and
      radiology. This recommendation was based on the consensus of the Board members of
      the Endoscopic Ultrasound Section of the Hungarian Gastroenterological Society.

PMID- 24681676
TI  - [The use of gliclazide in individualized sulfonylurea therapy].
AB  - In addition to the common blood glucose lowering effect, sulfonylurea compounds
      are different in many aspects from each other. Based on earlier findings the
      second generation gliclazide has special advantages within this group. Although
      the number of experimental and clinical observations on gliclazide is
      continuously increasing, these novel findings are not in the focus anymore due to
      the appearance of new antidiabetics. This article reviews recent experimental
      (effect on receptors, the absence of Epac2 activation, antioxidant properties,
      possible incentive of factors participating in beta-cell differentiation) and
      pharmacogenomic data, and compares them with clinical observations obtained from
      gliclazide treatment (hypoglycemias, parameters of cardiovascular outcome). The
      data underline the advantages of gliclazide, the highly pancreas-selective
      nature, preservation of the ischemic precondition, favourable hemodynamic
      properties and potential reduction of the beta-cell loss as compared to other
      compounds of the group. However, gliclazide is not free from disadvantages
      characteristic to sulfonylureas in general (blood glucose independent insulin
      stimulation, beta-cell depletion). Comparing gliclazide with other derivatives of
      the group, the above data indicate individual benefits for the application when
      sulfonylurea compound is the drug of choice.

PMID- 24681677
TI  - [Tissue fixation in clinical practice: the 120-year-old formalin].
AB  - Formalin, the saturated watery solution of formaldehyde is used in every health
      care institution worldwide as an effective and cheap tissue fixative. The
      beneficial effect of the formaldehyde solution was discovered and published
      exactly 120 years ago and, despite significant technological developments, the
      formula is still used in the same way. However, tissue based molecular techniques
      including multiple gene mutation testing from isolated DNA require a highly
      standardized tissue preservation procedure and the strict control of the
      composition of the fixative solution applied.

PMID- 24681678
TI  - [Professor Ferenc Farago, Head of the Institute of Microbiology, 1948-1950].

PMID- 24681680
TI  - Imaging in multiple sclerosis and related disorders.

PMID- 24681682
TI  - Role of nitrification in the biodegradation of selected artificial sweetening
      agents in biological wastewater treatment process.
AB  - The biodegradation of the six artificial sweetening agents including acesulfame
      (ACE), aspartame (ASP), cyclamate (CYC), neohesperidindihydrochalcone (NHDC),
      saccharin (SAC), and sucralose (SUC) by nitrifying activated sludge was first
      examined. Experimental results showed that ASP and NHDC were the most easily
      degradable compounds even in the control tests. CYC and SAC were efficiently
      biodegraded by the nitrifying activated sludge, whereas ACE and SUC were poorly
      removed. However, the biodegradation efficiencies of the ASs were increased with
      the increase in initial ammonium concentrations in the bioreactors. The
      association between nitrification and co-metabolic degradation was investigated
      and a linear relationship between nitrification rate and co-metabolic
      biodegradation rate was observed for the target artificial sweeteners (ASs). The
      contribution of heterotrophic microorganisms and autotrophic ammonia oxidizers in
      biodegradation of the ASs was elucidated, of which autotrophic ammonia oxidizers
      played an important role in the biodegradation of the ASs, particularly with
      regards to ACE and SUC. 

PMID- 24681681
TI  - Hydrogen production from cheese whey with ethanol-type fermentation: effect of
      hydraulic retention time on the microbial community composition.
AB  - The effects of different hydraulic retention times (HRTs) of 4, 2, and 1h and
      varying sources of inoculum (sludge from swine and sludge from poultry) on the
      hydrogen production in two anaerobic fluidized bed reactors (AFBRs) were
      evaluated. Cheese whey was used as a substrate, and 5000mgCODL(-1) was applied.
      The highest hydrogen yield (HY) of 1.33molmol(-1) lactose and highest ethanol
      yield (EtOHY) of 1.22molEtOHmol(-1) lactose were obtained at the highest HRT
      (4h). When the reactors were operated at an HRT of 1h, methane (0.68LCH4h(-1)L(
      1)) was produced concurrently with hydrogen (0.51LH2h(-1)L(-1)). The major
      metabolites observed were soluble ethanol, methanol, acetic acid, and butyric
      acid. Cloning of the 16S rRNA gene sequences indicated that the microbial
      community were affiliated with the genera Selenomonas sp. (69% of the sequences),
      and Methanobacterium sp. (98% of the sequences). 

PMID- 24681683
TI  - Pilot-scale continuous recycling of growth medium for the mass culture of a
      halotolerant Tetraselmis sp. in raceway ponds under increasing salinity: a novel
      protocol for commercial microalgal biomass production.
AB  - The opportunity to recycle microalgal culture medium for further cultivation is
      often hampered by salinity increases from evaporation and fouling by dissolved
      and particulate matter. In this study, the impact of culture re-use after electro
      flocculation of seawater-based medium on growth and biomass productivity of the
      halotolerant green algal strain Tetraselmis sp., MUR 233, was investigated in
      pilot-scale open raceway ponds over 5months. Despite a salinity increase from
      5.5% to 12% (w/v) NaCl, Tetraselmis MUR 233 grown on naturally DOC-enriched
      recycled medium produced 48-160% more ash free dry weight (AFDW) biomass daily
      per unit pond area than when grown on non-recycled medium. A peak productivity of
      37.5+/-3.1gAFDWm(-2)d(-1) was reached in the recycled medium upon transition from
      ~14% to ~7% NaCl. The combination of high biomass-yielding mixotrophic growth
      under high salinity has been proven to be a successful sustainable cultivation
      strategy. 

PMID- 24681684
TI  - Depletion of the Trypanosome Pumilio domain protein PUF2 or of some other
      essential proteins causes transcriptome changes related to coding region length.
AB  - Pumilio domain RNA-binding proteins are known mainly as posttranscriptional
      repressors of gene expression that reduce mRNA translation and stability.
      Trypanosoma brucei has 11 PUF proteins. We show here that PUF2 is in the cytosol,
      with roughly the same number of molecules per cell as there are mRNAs. Although
      PUF2 exhibits a low level of in vivo RNA binding, it is not associated with
      polysomes. PUF2 also decreased reporter mRNA levels in a tethering assay,
      consistent with a repressive role. Depletion of PUF2 inhibited growth of
      bloodstream-form trypanosomes, causing selective loss of mRNAs with long open
      reading frames and increases in mRNAs with shorter open reading frames.
      Reexamination of published RNASeq data revealed the same trend in cells depleted
      of some other proteins. We speculate that these length effects could be caused by
      inhibition of the elongation phase of transcription or by an influence of
      translation status or polysomal conformation on mRNA decay. 

PMID- 24681685
TI  - Modeling the transcriptional regulatory network that controls the early hypoxic
      response in Candida albicans.
AB  - We determined the changes in transcriptional profiles that occur in the first
      hour following the transfer of Candida albicans to hypoxic growth conditions. The
      impressive speed of this response is not compatible with current models of fungal
      adaptation to hypoxia that depend on the depletion of sterol and heme. Functional
      analysis using Gene Set Enrichment Analysis (GSEA) identified the Sit4
      phosphatase, Ccr4 mRNA deacetylase, and Sko1 transcription factor (TF) as
      potential regulators of the early hypoxic response. Cells mutated in these and
      other regulators exhibit a delay in their transcriptional responses to hypoxia.
      Promoter occupancy data for 29 TFs were combined with the transcriptional
      profiles of 3,111 in vivo target genes in a Network Component Analysis (NCA) to
      produce a model of the dynamic and highly interconnected TF network that controls
      this process. With data from the TF network obtained from a variety of sources,
      we generated an edge and node model that was capable of separating many of the
      hypoxia-upregulated and -downregulated genes. Upregulated genes are centered on
      Tye7, Upc2, and Mrr1, which are associated with many of the gene promoters that
      exhibit the strongest activations. The connectivity of the model illustrates the
      high redundancy of this response system and the challenges that lie in
      determining the individual contributions of specific TFs. Finally, treating cells
      with an inhibitor of the oxidative phosphorylation chain mimics most of the early
      hypoxic profile, which suggests that this response may be initiated by a drop in
      ATP production. 

PMID- 24681689
TI  - Introduction to Special Issue on Design Parameters for Cluster Randomized Trials
      in Education.

PMID- 24681687
TI  - Role of force-sensitive amyloid-like interactions in fungal catch bonding and
      biofilms.
AB  - The Candida albicans Als adhesin Als5p has an amyloid-forming sequence that is
      required for aggregation and formation of model biofilms on polystyrene. Because
      amyloid formation can be triggered by force, we investigated whether laminar flow
      could activate amyloid formation and increase binding to surfaces. Shearing
      Saccharomyces cerevisiae cells expressing Als5p or C. albicans at 0.8 dyne/cm(2)
      increased the quantity and strength of cell-to-surface and cell-to-cell binding
      compared to that at 0.02 dyne/cm(2). Thioflavin T fluorescence showed that the
      laminar flow also induced adhesin aggregation into surface amyloid nanodomains in
      Als5p-expressing cells. Inhibitory concentrations of the amyloid dyes thioflavin
      S and Congo red or a sequence-specific anti-amyloid peptide decreased binding and
      biofilm formation under flow. Shear-induced binding also led to formation of
      robust biofilms. There was less shear-activated increase in adhesion, thioflavin
      fluorescence, and biofilm formation in cells expressing the amyloid-impaired
      V326N-substituted Als5p. Similarly, S. cerevisiae cells expressing Flo1p or
      Flo11p flocculins also showed shear-dependent binding, amyloid formation, biofilm
      formation, and inhibition by anti-amyloid compounds. Together, these results show
      that laminar flow activated amyloid formation and led to enhanced adhesion of
      yeast cells to surfaces and to biofilm formation. 

PMID- 24681686
TI  - Calcineurin-Crz1 signaling in lower eukaryotes.
AB  - Calcium ions are ubiquitous intracellular messengers. An increase in the
      cytosolic Ca(2+) concentration activates many proteins, including calmodulin and
      the Ca(2+)/calmodulin-dependent protein phosphatase calcineurin. The phosphatase
      is conserved from yeast to humans (except in plants), and many target proteins of
      calcineurin have been identified. The most prominent and best-investigated
      targets, however, are the transcription factors NFAT (nuclear factor of activated
      T cells) in mammals and Crz1 (calcineurin-responsive zinc finger 1) in yeast. In
      recent years, many orthologues of Crz1 have been identified and characterized in
      various species of fungi, amoebae, and other lower eukaryotes. It has been shown
      that the functions of calcineurin-Crz1 signaling, ranging from ion homeostasis
      through cell wall biogenesis to the building of filamentous structures, are
      conserved in the different organisms. Furthermore, frequency-modulated gene
      expression through Crz1 has been discovered as a striking new mechanism by which
      cells can coordinate their response to a signal. In this review, I focus on the
      latest findings concerning calcineurin-Crz1 signaling in fungi, amoebae and other
      lower eukaryotes. I discuss the potential of Crz1 and its orthologues as putative
      drug targets, and I also discuss possible parallels with calcineurin-NFAT
      signaling in mammals. 

PMID- 24681690
TI  - Sensitivity plots for confounder bias in the single mediator model.
AB  - BACKGROUND: Causal inference continues to be a critical aspect of evaluation
      research. Recent research in causal inference for statistical mediation has
      focused on addressing the sequential ignorability assumption; specifically, that
      there is no confounding between the mediator and the outcome variable.
      OBJECTIVES: This article compares and contrasts three different methods for
      assessing sensitivity to confounding and describes the graphical depiction of
      these methods. DESIGN: Two types of data were used to fully examine the plots for
      sensitivity analysis. The first type was generated data from a single mediator
      model with a confounder influencing both the mediator and the outcome variable.
      The second was data from an actual intervention study. With both types of data,
      situations are examined where confounding has a large effect and a small effect.
      SUBJECTS: The nonsimulated data were from a large intervention study to decrease
      intentions to use steroids among high school football players. We demonstrate one
      situation where confounding is likely and another situation where confounding is
      unlikely. CONCLUSIONS: We discuss how these methods could be implemented in
      future mediation studies as well as the limitations and future directions for
      these methods.

PMID- 24681692
TI  - Semantic fluency: cognitive basis and diagnostic performance in focal dementias
      and Alzheimer's disease.
AB  - Semantic fluency is widely used both as a clinical test and as a basic tool for
      understanding how humans extract information from the semantic store. Recently,
      major efforts have been made to devise fine-grained scoring procedures to measure
      the multiple cognitive processes underlying fluency performance. Nevertheless, it
      is still unclear how many and which independent components are necessary to
      thoroughly describe performance on the fluency task. Furthermore, whether a
      combination of multiple indices can improve the diagnostic performance of the
      test should be assessed. In this study, we extracted multiple indices of
      performance on the semantic fluency test from a large sample of healthy controls
      (n = 307) and patients (n = 145) suffering from three types of focal dementia or
      Alzheimer's Disease (AD). We found that five independent components underlie
      semantic fluency performance. We argue that these components functionally map
      onto the generation and application of a search strategy (component 2), to the
      monitoring of the overall sequence to avoid repetitions (component 3) and out-of
      category items (component 4), and to the full integrity of the semantic store
      (component 5). The integrated and effective work of all these components would
      relate to a "general effectiveness" component (component 1). Importantly, while
      all the focal dementia groups were equally impaired on general effectiveness
      measures, they showed differential patterns of failure in the other components.
      This finding suggests that the cognitive deficit that impairs fluency differs
      among the three focal dementia groups: a semantic store deficit in the semantic
      variant of primary progressive aphasia (sv-PPA), a strategy deficit in the non
      fluent variant of primary progressive aphasia (nfv-PPA), and an initiation
      deficit in the behavioural variant of fronto-temporal dementia (bv-FTD). Finally,
      we showed that the concurrent use of multiple fluency indices improves the
      diagnostic accuracy of semantic fluency both for focal dementias and for AD. More
      generally, our study suggests that a formal evaluation of fine-grained patterns
      of performance would improve the diagnostic accuracy of neuropsychological tests.

PMID- 24681691
TI  - A biochemical analysis of the interaction of Porphyromonas gingivalis HU PG0121
      protein with DNA.
AB  - K-antigen capsule, a key virulence determinant of the oral pathogen Porphyromonas
      gingivalis, is synthesized by proteins encoded in a series of genes transcribed
      as a large polycistronic message. Previously, we identified a 77-base pair
      inverted repeat region with the potential to form a large stem-loop structure at
      the 5' end of this locus. PG0121, one of two genes flanking the capsule operon,
      was found to be co-transcribed with the operon and to share high similarity to
      the DNA binding protein HU from Escherichia coli. A null mutation in PG0121
      results in down-regulation of transcription of the capsule synthesis genes and
      production of capsule. Furthermore, we have also shown that PG0121 gene can
      complement multiple deficiencies in a strain of E. coli that is deficient for
      both the alpha and beta subunits of HU. Here, we examined the biochemical
      properties of the interaction of PG0121 to DNA with the emphasis on the kinds of
      nucleic acid architectures that may be encountered at the 77-bp inverted repeat.
      We have concluded that although some DNA binding characteristics are shared with
      E. coli HU, HU PG0121 also shows some distinct characteristics that set it apart
      from other HU-like proteins tested to date. We discuss our results in the context
      of how PG0121 may affect the regulation of the K-antigen capsule expression. 

PMID- 24681693
TI  - Transcriptional profiling of cells sorted by RNA abundance.
AB  - We have developed a quantitative technique for sorting cells on the basis of
      endogenous RNA abundance, with a molecular resolution of 10-20 transcripts. We
      demonstrate efficient and unbiased RNA extraction from transcriptionally sorted
      cells and report a high-fidelity transcriptome measurement of mouse induced
      pluripotent stem cells (iPSCs) isolated from a heterogeneous reprogramming
      culture. This method is broadly applicable to profiling transcriptionally
      distinct cellular states without requiring antibodies or transgenic fluorescent
      proteins. 

PMID- 24681695
TI  - Abandonment of childhood cancer treatment in Western Kenya.
AB  - BACKGROUND: The most important reason for childhood cancer treatment failure in
      low-income countries is treatment abandonment. OBJECTIVE: The aim of this study
      was to explore reasons for childhood cancer treatment abandonment and assess the
      clinical condition of these children. DESIGN: This was a descriptive study using
      semistructured questionnaires. Home visits were conducted to interview families
      of childhood cancer patients, diagnosed between January 2007 and January 2009,
      who had abandoned treatment at the Moi Teaching and Referral Hospital (MTRH).
      RESULTS: Between January 2007 and January 2009, 222 children were newly diagnosed
      with a malignancy at MTRH. Treatment outcome was documented in 180 patients. Of
      these 180 patients, 98 (54%) children abandoned treatment. From December 2011
      until August 2012, 53 (54%) of the 98 families were contacted. Due to lack of
      contact information, 45 families were untraceable. From 53 contacted families, 46
      (87%) families agreed to be interviewed. Reasons for abandonment were reported by
      26 families, and they were diverse. Most common reasons were financial
      difficulties (46%), inadequate access to health insurance (27%) and
      transportation difficulties (23%). Most patients (72%) abandoned treatment after
      the first 3 months had been completed. Of the 46 children who abandoned
      treatment, 9 (20%) were still alive: 6 (67%) of these children looked healthy and
      3 (33%) ill. The remaining 37 (80%) children had passed away. CONCLUSIONS:
      Prevention of childhood cancer treatment abandonment requires improved access to
      health insurance, financial or transportation support, proper parental education,
      psychosocial guidance and ameliorated communication skills of healthcare
      providers.

PMID- 24681694
TI  - Quantifying Drosophila food intake: comparative analysis of current methodology.
AB  - Food intake is a fundamental parameter in animal studies. Despite the prevalent
      use of Drosophila in laboratory research, precise measurements of food intake
      remain challenging in this model organism. Here, we compare several common
      Drosophila feeding assays: the capillary feeder (CAFE), food labeling with a
      radioactive tracer or colorimetric dye and observations of proboscis extension
      (PE). We show that the CAFE and radioisotope labeling provide the most consistent
      results, have the highest sensitivity and can resolve differences in feeding that
      dye labeling and PE fail to distinguish. We conclude that performing the
      radiolabeling and CAFE assays in parallel is currently the best approach for
      quantifying Drosophila food intake. Understanding the strengths and limitations
      of methods for measuring food intake will greatly advance Drosophila studies of
      nutrition, behavior and disease. 

PMID- 24681696
TI  - Deaf culture: competencies and best practices.
AB  - To successfully navigate in the hearing world, deaf individuals must be able to
      read and write to bridge the gap when others do not know American Sign Language.
      Unfortunately, 90% of deaf children are born to hearing parents and do not
      develop language skills early on, which negatively impacts their ability to
      access health information and healthcare. Healthcare providers must ensure they
      provide culturally competent care and their practices accommodate the needs of
      deaf patients to mitigate communication barriers and ensure equitable care with
      positive health outcomes.

PMID- 24681697
TI  - Herpes zoster: A rash demanding careful evaluation.
AB  - This article discusses the incidence, epidemiology, clinical presentation,
      diagnosis, and treatment of herpes zoster, complications such as postherpetic
      neuralgia, and prevention through vaccination. Information on vaccine cost and
      insurance coverage is provided as well as two case studies illustrating various
      clinical presentations.

PMID- 24681699
TI  - Pentachlorophenol toxicity to a mixture of Microcystis aeruginosa and Chlorella
      vulgaris cultures.
AB  - Pentachlorophenol (PCP) is a priority pollutant due to its persistence and high
      toxicity. For the first time, PCP effects were investigated at laboratory scale
      on co-cultures of two ubiquitous freshwater phytoplankton species: the
      cyanobacterium Microcystis aeruginosa and the microalgae Chlorella vulgaris. The
      cells were exposed to environmental levels of PCP for 10 days in Fraquil culture
      medium, at nominal concentrations from 0.1 to 10,000 MUg L(-1). Growth was
      assessed by area under growth curve (cell count vs. time). The phytoplankton
      community structure can be changed as a consequence of a PCP contamination. Low
      MUg L(-1) levels of PCP are advantageous to M. aeruginosa. This is the first
      report of the promoting effect of PCP on the growth of aquatic cyanobacteria,
      using mixtures with microalgae. As a result of the direct toxic effects of high
      PCP concentrations on M. aeruginosa, C. vulgaris cell count increased given that
      in biological controls M. aeruginosa inhibited the C. vulgaris growth. At 16.7 mg
      L(-1), PCP already had direct toxic effects also on the microalga. The pH of
      culture medium tended to decrease with increasing PCP concentrations, which was
      mostly related to the growth inhibition of cyanobacterium caused by PCP. The PCP
      concentration was stable in the co-cultures, which differed from what has been
      observed in monocultures of the same two species. Short-term laboratory assays
      with two phytoplankton species gives important information on the species
      interactions, namely possible direct and indirect effects of a toxicant, and must
      be considered in ecotoxicity studies regarding environmental extrapolations.

PMID- 24681698
TI  - Gabapentin inhibits bortezomib-induced mechanical allodynia through supraspinal
      action in mice.
AB  - Bortezomib, an inhibitor of proteasome holoenzyme, is used to treat relapsed and
      refractory multiple myeloma. Peripheral neuropathy is a treatment-limiting
      adverse effect of bortezomib and is very difficult to control. In this study, we
      examined the efficacy of gabapentin in inhibiting bortezomib-induced peripheral
      neuropathy. Single intravenous injections of bortezomib (0.03 - 0.3 mg/kg) dose
      dependently induced mechanical allodynia with a peak effect 12 days after
      injection. Bortezomib (0.3 mg/kg) also caused mechanical hyperalgesia, but
      neither affected thermal nociception nor induced cold allodynia. Bortezomib
      increased the response of the saphenous nerve to weak punctate stimulation but
      not response to cool stimulation of the skin. When administered 12 days after
      bortezomib injection, oral and intracisternal gabapentin markedly inhibited
      mechanical allodynia. Intrathecal, but not intraplantar, gabapentin had a
      tendency to reduce mechanical allodynia. The antiallodynic activity of orally
      administered gabapentin was suppressed by noradrenaline, but not serotonin,
      depletion in the spinal cord. Bortezomib did not affect the expression levels of
      the calcium channel alpha2delta-1 subunit, a high-affinity binding site of
      gabapentin, in the plantar skin, spinal cord, medulla oblongata, and pons. These
      results suggest that gabapentin inhibits bortezomib-induced mechanical allodynia,
      most likely through the activation of the descending noradrenergic system.

PMID- 24681700
TI  - Balance between herbicidal activity and toxicity effect: a case study of the
      joint effects of triazine and phenylurea herbicides on Selenastrum capricornutum
      and Photobacterium phosphoreum.
AB  - The use of herbicide mixtures has become a cost-effective strategy against the
      evolution of herbicide resistance to protect global food production. Much
      research has focused on investigating either the herbicidal activities or the
      toxicity effects of herbicides; however, few of them have investigated both
      factors. This study investigates the balance between herbicidal activity for
      Selenastrum capricornutum and toxicity effect toward Photobacterium phosphoreum
      by determining the joint effects of triazine (simetryn, atrazine, prometon and
      prometryn) and phenylurea (fenuron, monuron, monolinuron and diuron) herbicides.
      The results showed that among the four triazines, only simetryn exhibited a
      unique effect (formation of a pi-sigma bond with the D1 microalga protein and an
      H-bond with the Luc photobacterial protein); and among 16 triazine-phenylurea
      binary mixtures, only the mixtures containing simetryn resulted in TU1 values
      (herbicidal activities of mixtures on S. capricornutum) >TU2 values (toxicity
      effects of mixtures on P. phosphoreum). However, the other 12 mixtures, which did
      not contain simetryn, showed the opposite result (TU1<TU2). A comparison of TU1
      with TU2 showed that additive effects occurred more frequently for TU1, whereas
      antagonism effects occurred more frequently for TU2. Based on these results, a
      preliminary mechanistic hypothesis of herbicide mixtures was proposed. Meanwhile,
      some suggestions are provided firstly for herbicide combinations based on the
      balance between herbicidal activity and toxicity effect, which will encourage
      thoughtful efforts for how to best combine herbicides in a sustainable way.

PMID- 24681701
TI  - Stress resilience in male adolescents and subsequent stroke risk: cohort study.
AB  - OBJECTIVE: Exposure to psychosocial stress has been identified as a possible
      stroke risk, but the role of stress resilience which may be relevant to chronic
      exposure is uncertain. We investigated the association of stress resilience in
      adolescence with subsequent stroke risk. METHODS: Register-based cohort study.
      Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010
      using information from Swedish registers. Cox regression estimated the
      association of stress resilience with stroke, after adjustment for established
      stroke risk factors. RESULTS: Some 3411 diagnoses of first stroke were
      identified. Lowest stress resilience (21.8%) compared with the highest (23.7%)
      was associated with increased stroke risk, producing unadjusted HR (with 95% CIs)
      of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to
      1.63) after adjustment for markers of socioeconomic circumstances in childhood;
      and after further adjustment for markers of development and disease in
      adolescence (blood pressure, cognitive function and pre-existing cardiovascular
      disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further
      adjustment for markers of physical fitness (BMI and physical working capacity) in
      adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was
      subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude
      associations for fatal rather than non-fatal, and for haemorrhagic rather than
      ischaemic stroke. CONCLUSIONS: Stress susceptibility and, therefore, psychosocial
      stress may be implicated in the aetiology of stroke. This association may be
      explained, in part, by poorer physical fitness. Effective prevention might focus
      on behaviour/lifestyle and psychosocial stress.

PMID- 24681702
TI  - A risk factor analysis of prospective symptomatic haemorrhage in adult patients
      with cerebral cavernous malformation.
AB  - OBJECTIVE: The purpose of this study was to assess the risk factors of
      prospective symptomatic haemorrhage in a large series of adult patients with
      cerebral cavernous malformation (CM). METHODS: Three hundred twenty-six patients
      >18 years of age with 410 CMs were evaluated retrospectively. Symptomatic
      haemorrhage was defined as new clinical symptoms with radiographic features of
      haemorrhage. Clinical data and the characteristics of CM were analysed. MR
      appearance was divided into three groups according to Zabramski's classification.
      RESULTS: The overall haemorrhage rate of CM was 4.46% per lesion-year. The
      overall annual haemorrhage rate according to MR appearance was as follows: type
      I, 9.47%; type II, 4.74%; and type III, 1.43%. A multivariate analysis revealed
      that prior symptomatic haemorrhage (p<0.001) and MR appearance (p<0.001) were
      statistically significant. After multiple comparisons, type I (p<0.001) and type
      II (p=0.016) showed higher haemorrhage risk than type III. However, no
      significant difference in haemorrhage rate was observed between type I and type
      II (p=0.105). Other variables including female gender, age, location,
      multiplicity, hypertension, size and associated venous angioma were not
      significant. The haemorrhage rates based on risk factors were estimated at 3
      years as follows: 33.77% in patients with prior haemorrhage versus 7.54% in
      patients without prior haemorrhage (p<0.001); type I, 27.62% vs type II, 15.44%
      vs type III, 5.38% (p<0.001). CONCLUSIONS: Prior symptomatic haemorrhage and MR
      appearance could be related to prospective symptomatic CM haemorrhage in adults.
      A prospective multicentre observational study is necessary to confirm our
      results.

PMID- 24681703
TI  - Comparison of platelet parameters in thrombocytopenic patients associated with
      acute myeloid leukemia and primary immune thrombocytopenia.
AB  - Thrombocytopenia is caused by insufficient production and excessive destruction
      of platelets. Recent improvement of automated blood cell analyzers has allowed
      measurement of several platelet parameters, providing better understanding of the
      underlying mechanisms of thrombocytopenia. We investigated the significance of
      platelet parameters in thrombocytopenic patients. Thrombocytopenic patients
      (platelet <100 * 10/MUl) who were newly diagnosed with acute myeloid leukemia and
      primary immune thrombocytopenia were enrolled, and platelet, mean platelet
      volume, platelet distribution width, platelet crit, mean platelet component, mean
      platelet mass, and large platelet count were measured, and the percentages of
      large platelets were calculated. The parameters were also measured in the
      reference population. The mean values of each parameter were as follows:
      platelet, 259 * 10/MUl; mean platelet volume, 7.9 fl; platelet distribution
      width, 51.3%; platelet crit, 0.20%; mean platelet component, 26.0 g/dl; mean
      platelet mass, 1.9 pg; large platelet, 4.7 * 10/MUl; large platelet percentage,
      1.7%. In comparison with acute myeloid leukemia patients, patients with primary
      immune thrombocytopenia showed significantly higher mean platelet volume,
      platelet distribution width, mean platelet component, mean platelet mass, large
      platelet, and large platelet % (P < 0.05). Because of increased destruction of
      platelets, primary immune thrombocytopenia patients have increased mean platelet
      volume, platelet distribution width, mean platelet component, mean platelet mass,
      large platelet, and large platelet percentage compared with acute myeloid
      leukemia patients who have ineffective platelet production. Parameters measured
      by automated analyzer provide better understanding of thrombopoiesis in the bone
      marrow and the status of the peripheral blood in the clinical field. 

PMID- 24681705
TI  - Differences of isolated dental stem cells dependent on donor age and consequences
      for autologous tooth replacement.
AB  - OBJECTIVE: Autologous therapy via stem cell-based tissue regeneration is an aim
      to rebuild natural teeth. One option is the use of adult stem cells from the
      dental pulp (DPSCs), which have been shown to differentiate into several types of
      tissue in vitro and in vivo, especially into tooth-like structures. DPSCs are
      mainly isolated from the dental pulp of third molars routinely extracted for
      orthodontic reasons. Due to the extraction of third molars at various phases of
      life, DPSCs are isolated at different developmental stages of the tooth. DESIGN:
      The present study addressed the question whether DPSCs from patients of different
      ages were similar in their growth characteristics with respect to the stage of
      tooth development. Therefore DPSCs from third molars of 12-30 year-old patients
      were extracted, and growth characteristics, e.g. doubling time and maximal cell
      division potential were analysed. In addition, pulp and hard dental material
      weight were recorded. RESULTS: Irrespective of the age of patients almost all
      isolated cells reached 40-60 generations with no correlation between maximal cell
      division potential and patient age. Cells from patients <22 years showed a
      significantly faster doubling time than the cells from patients >=22 years.
      CONCLUSION: The age of patients at the time of stem cell isolation is not a
      crucial factor concerning maximal cell division potential, but does have an
      impact on the doubling time. However, differences in individuals regarding growth
      characteristics were more pronounced than age-dependent differences.

PMID- 24681704
TI  - Monitoring anticoagulation in patients with an unreliable prothrombin
      time/international normalized ratio: factor II versus chromogenic factor X
      testing.
AB  - The international normalized ratio (INR) can be unreliable in patients with lupus
      anticoagulants (LACs) or other conditions affecting baseline testing. Alternative
      methods to assess anticoagulation on warfarin through measures of vitamin K
      dependent factor activity by clot based or chromogenic assays may be necessary.
      In this patient population, the ideal method is unknown. Thirty-six patients
      stable on warfarin with LAC or unreliable INR testing had an INR, a prothrombin
      time-based clotting assay for factor II (FII) activity, and a chromogenic assay
      for factor X (CFX) activity were performed simultaneously. Eighty-nine sets of
      measurements were obtained of which 83 sets included all three assays. CFX and
      FII levels were well correlated (r = 0.92) in all patients and in 26 patients
      with a documented antiphospholipid antibody (r = 0.93). Parallel testing was seen
      in 99% of FII assays. Sixty-one percent of CFX and 57% of FII were within the
      therapeutic range. In 32 CFX and FII pairs wherein assessment of anticoagulation
      was discordant, 16 CFX agreed with INR and 13 FII agreed with INR (McNemar's, chi
      = 0.14, P = 0.7). The number of times tests were discrepant was not statistically
      different between CFX and FII (P = 0.36). CFX and FII activity are well
      correlated in patients that require alternative monitoring of warfarin. Either
      test can be used in this population. 

PMID- 24681706
TI  - Pleomorphic adenoma of oral minor salivary glands: An investigation of its
      neoplastic potential based on apoptosis, mucosecretory activity and cellular
      proliferation.
AB  - OBJECTIVE: The aim of this study was to investigate the neoplastic potential of
      the PA of minor oral salivary glands measured by apoptosis (Bcl-2, Bax and p53),
      mucosecretory activity (MUC1), and cellular proliferation (Ki-67). DESIGN: Thirty
      one cases of PA of the oral cavity and four controls (C) taken from normal oral
      minor salivary glands were analyzed using the immunohistochemistry technique. The
      proteins were detected utilizing a semi-quantitative method (scores) as follows:
      (-) negative <=5%, (+) low 6-25%, (++) moderate 26-50% and (+++) high >50% of
      positive tumour cells. The apoptotic indices were evaluated by the ratio Bcl
      2/Bax. Non-parametric comparison and correlation tests were used for analysis.
      RESULTS: The data showed high staining of anti-apoptotic protein Bcl-2 in both
      groups (PA=57.9%; C=67.7%) and a significantly lower expression of pro-apoptotic
      protein Bax (PA=22.7%; C=97.7%) and MUC1 (PA=14%; C=82.3%) in PA than in C
      (p<0.001). On the other hand, a similar expression of Ki-67 and p53 proteins
      (<=5%) was seen in both PA and C. In PA, only 2/31 cases showed the ratio Bcl
      2/Bax<1.There was no difference in cellular expression with regard to clinical
      variables or clinical outcome (p>0.05). CONCLUSION: The neoplastic potential of
      PA could be associated with an imbalance in apoptotic processes and a lower index
      of cellular proliferation. Mucosecretory activity does not play a significant
      role in primary PA.

PMID- 24681708
TI  - Remarkably enhanced photocatalytic activity of ordered mesoporous carbon/g-C3N4
      composite photocatalysts under visible light.
AB  - Ordered mesoporous carbon/g-C3N4 (OMC/g-C3N4) composites with efficient
      photocatalytic activity under visible light irradiation were prepared by a facile
      heating method. The as-prepared OMC/g-C3N4 composites were thoroughly
      characterized by X-ray diffraction, Fourier transform infrared spectroscopy,
      elemental analyses, transmission electron microscopy with energy dispersion X-ray
      spectroscopy, N2 adsorption-desorption analysis, UV-vis diffuse reflectance
      spectroscopy and photoluminescence spectroscopy. The photocatalytic activities
      were evaluated by degrading Rhodamine B dye, and OMC/g-C3N4 composites exhibited
      much higher photocatalytic activities than pristine g-C3N4. Moreover, the
      catalysts retained good stability and the photodegradation efficiency hardly
      changed after five cycles. The degradation rate of the OMC/g-C3N4 photocatalyst
      was almost 10 times as high as that of the pristine g-C3N4, which indicated that
      OMC played an important role in the remarkable improvement of photocatalytic
      activity. The significant enhancement in photodegradation activity over the OMC/g
      C3N4 catalyst could be ascribed to the combined effects coming from the enhanced
      visible light adsorption, enriched adsorption of the dye on the catalyst and
      subsequent efficient separation of photogenerated electrons and holes. In
      addition, a possible mechanism for the photodegradation process was proposed on
      the basis of active species scavenging experiments. 

PMID- 24681707
TI  - Identification of heat shock protein 32 (Hsp32) as a novel target in acute
      lymphoblastic leukemia.
AB  - Heat shock proteins (Hsp) are increasingly employed as therapeutic targets in
      oncology. We have shown that Hsp32, also known as heme oxygenase-1 (HO-1), serves
      as survival factor and potential target in Ph+ chronic myeloid leukemia. We here
      report that primary cells and cell lines derived from patients with acute
      lymphoblastic leukemia (ALL) express Hsp32 mRNA and the Hsp32 protein in a
      constitutive manner. Highly enriched CD34+/CD38- ALL stem cells also expressed
      Hsp32. Two Hsp32-targeting drugs, pegylated zinc protoporphyrine (PEG-ZnPP) and
      styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), induced apoptosis and
      growth arrest in the BCR/ABL1+ cell lines, in Ph- lymphoblastic cell lines and in
      primary Ph+ and Ph- ALL cells. The effects of PEG-ZnPP and SMA-ZnPP on growth of
      leukemic cells were dose-dependent. In Ph+ ALL, major growth-inhibitory effects
      of the Hsp32-targeting drugs were observed in imatinib-sensitive and imatinib
      resistant cells. Hsp32-targeting drugs were found to synergize with imatinib,
      nilotinib, and bendamustine in producing growth inhibition and apoptosis in Ph+
      ALL cells. A siRNA against Hsp32 was found to inhibit growth and survival of ALL
      cells and to synergize with imatinib in suppressing the growth of ALL cells. In
      conclusion, Hsp32 is an essential survival factor and potential new target in
      ALL. 

PMID- 24681710
TI  - Oenological prefermentation practices strongly impact yeast population dynamics
      and alcoholic fermentation kinetics in Chardonnay grape must.
AB  - Yeast species of Hanseniaspora and Candida genus are predominant during the early
      stages of winemaking, while species of Metschnikowia, Pichia, Zygoascus,
      Issatchenkia, Torulaspora and other genera are present at lower population
      levels. The impact of common oenological practices on yeast dynamics during the
      prefermentative stage and the early stage of alcoholic fermentation (AF) remains
      elusive. In this work, the effect of four prefermentative oenological practices
      (clarification degree, temperature, sulphite and starter yeast addition) on yeast
      dynamics was evaluated in a Chardonnay grape must. The growth curves of four
      genus or species, namely Saccharomyces spp., Hanseniaspora spp., Candida
      zemplinina and Torulaspora delbrueckii, were followed by quantitative PCR. The
      fermentation kinetics were also recorded, as well as the production of acetic
      acid. Variance analysis allowed determining the effect of each practice and their
      interaction factors, as well as their relative importance on yeast dynamics and
      fermentation kinetics. Our experimental design showed that the population
      dynamics of the four species were differently impacted by the oenological
      practices, with some species being more sensitive than others to the
      clarification degree (C. zemplinina), sulphite addition (Saccharomyces spp.),
      starter yeast inoculation (Hanseniaspora spp.) or prefermentation temperature (T.
      delbrueckii). Significant interaction effects between practices were revealed,
      highlighting the interest of experimental design allowing interaction analysis,
      as some factors may buffer the effect of other ones. Hanseniaspora genus showed
      atypical behaviour: growth dynamics showed a decrease during AF that we
      interpreted as early cellular lysis. In conclusion, this study provides new
      insights on the impact of common oenological practices on the dynamics of non
      Saccharomyces yeast that will be useful for a better management of mixed
      fermentation between S. cerevisiae and non-Saccharomyces yeasts. 

PMID- 24681709
TI  - Real-time light scattering tracking of gold nanoparticles- bioconjugated
      respiratory syncytial virus infecting HEp-2 cells.
AB  - Real-time tracking of virus invasion is crucial for understanding viral infection
      mechanism, which, however, needs simple and efficient labeling chemistry with
      improved signal-to-noise ratio. For that purpose, herein we investigated the
      invasion dynamics of respiratory syncytial virus (RSV) through dark-field
      microscopic imaging (iDFM) technique by using Au nanoparticles (AuNPs) as light
      scattering labels. RSV, a ubiquitous, non-segmented, pleiomorphic and negative
      sense RNA virus, is an important human pathogen in infants, the elderly, and the
      immunocompromised. In order to label the enveloped virus of paramyxoviridae
      family, an efficient streptavidin (SA)-biotin binding chemistry was employed,
      wherein AuNPs and RSV particles modified with SA and biotin, respectively,
      allowing the AuNP-modified RSVs to maintain their virulence without affecting the
      native activities of RSV, making the long dynamic visualization successful for
      the RSV infections into human epidermis larynx carcinoma cells. 

PMID- 24681711
TI  - Acetic acid bacteria isolated from grapes of South Australian vineyards.
AB  - Acetic acid bacteria (AAB) diversity from healthy, mould-infected and rot
      affected grapes collected from three vineyards of Adelaide Hills (South
      Australia) was analyzed by molecular typing and identification methods. Nine
      different AAB species were identified from the 624 isolates recovered: Four
      species from Gluconobacter genus, two from Asaia and one from Acetobacter were
      identified by the analysis of 16S rRNA gene and 16S-23S rRNA gene internal
      transcribed spacer. However, the identification of other isolates that were
      assigned as Asaia sp. and Ameyamaea chiangmaiensis required more analysis for a
      correct species classification. The species of Gluconobacter cerinus was the main
      one identified; while one genotype of Asaia siamensis presented the highest
      number of isolates. The number of colonies recovered and genotypes identified was
      strongly affected by the infection status of the grapes; the rot-affected with
      the highest number. However, the species diversity was similar in all the cases.
      High AAB diversity was detected with a specific genotype distribution for each
      vineyard. 

PMID- 24681712
TI  - Surgical site infection in women undergoing surgery for gynecologic cancer.
AB  - OBJECTIVES: The objectives of this study were to describe the rate and predictors
      of surgical site infection (SSI) after gynecologic cancer surgery and identify
      any association between SSI and postoperative outcome. MATERIALS AND METHODS:
      Patients with endometrial, cervical, or ovarian cancers from 2005 to 2011 were
      identified from the American College of Surgeons National Surgical Quality
      Improvement Program. The extent of surgical intervention was categorized into
      modified surgical complexity scoring (MSCS) system. Univariate and multivariate
      logistic regression analyses were used. Odds ratios were adjusted for patient
      demographics, comorbidities, preoperative laboratory values, and operative
      factors. RESULTS: Of 6854 patients, 369 (5.4%) were diagnosed with SSI. Surgical
      site infection after laparotomy was 3.5 times higher compared with minimally
      invasive surgery (7% vs 2%; P < 0.001). Among laparotomy group, independent
      predictors of SSI included endometrial cancer diagnosis, obesity, ascites,
      preoperative anemia, American Society of Anesthesiologists class greater than or
      equal to 3, MSCS greater than or equal to 3, and perioperative blood transfusion.
      Among laparoscopic cases, independent predictors of SSI included only
      preoperative leukocytosis and overweight. For patients with deep or organ space
      SSI, significant predictors included hypoalbuminemia, preoperative weight loss,
      respiratory comorbidities, MSCS greater than 4, and perioperative blood
      transfusion for laparotomy and only preoperative leukocytosis for minimally
      invasive surgery. Surgical site infection was associated with longer mean
      hospital stay and higher rate of reoperation, sepsis, and wound dehiscence.
      Surgical site infection was not associated with increased risk of acute renal
      failure or 30-day mortality. These findings were consistent in subset of patients
      with deep or organ space SSI. CONCLUSIONS: Seven percent of patients undergoing
      laparotomy for gynecologic malignancy developed SSI. Surgical site infection is
      associated with longer hospital stay and more than 5-fold increased risk of
      reoperation. In this study, we identified several risk factors for developing SSI
      among gynecologic cancer patients. These findings may contribute toward
      identification of patients at risk for SSI and the development of strategies to
      reduce SSI rate and potentially reduce the cost of care in gynecologic cancer
      surgery.

PMID- 24681713
TI  - Impact of ischemia-reperfusion on extracellular matrix processing and structure
      of the basement membrane of the heart.
AB  - PURPOSE: Acute ischemic injury is a strong inductor of cardiac remodelling,
      resulting in structural changes of the extracellular matrix (ECM) and basement
      membrane (BM). In a large animal model of ischemia-reperfusion (I/R) we
      investigated the post-ischemic liberation of the collagen-IV-fragments Tumstatin
      (TUM; 28 kDa-fragment of collagen-IV-alpha-3), Arresten (ARR; 26 kDa-fragment of
      collagen-IV-alpha-1) and Endorepellin (LG3, 85 kDa-fragment of perlecan) which
      are biologically active in angiogenesis and vascularization in the post-ischemic
      myocardium. METHODS AND RESULTS: In this blinded study, 30 pigs were randomized
      to 60 min of global I/R at either 4 degrees C or 32 degrees C or served as
      control. Three transmyocardial tissue samples were collected prior to ischemia
      and within 30 min and 150 min of reperfusion. Tissue content of TUM, ARR and LG3
      was analyzed by western blotting and immunostaining. Within 150 min of mild
      hypothermic I/R a significantly increased tissue content of ARR (0.17+/-0.14 vs.
      0.56+/-0.56; p = 0.001) and LG3 (1.13+/-0.34 vs. 2.51+/-1.71, p<0.001) was
      observed. In contrast, deep hypothermic I/R was not associated with a significant
      release of cleavage products. Cleavage of TUM remained unchanged irrespective of
      temperature. Increased matrix processing following mild hypothermia I/R is
      further supported by a >11fold elevation of creatine kinase (2075+/-2595 U/l vs.
      23248+/-6551 U/l; p<0.001) in the coronary sinus plasma samples. Immunostaining
      demonstrated no changes for ARR and LG3 presentation irrespective of temperature.
      In contrast, TUM significantly decreased in the BM surrounding cardiomyocytes and
      capillaries after mild and deep hypothermic I/R, thus representing structural
      alterations of the BM in these groups. CONCLUSION: The study demonstrates an
      early temperature-dependent processing of Col-IV as major component of the BM of
      cardiomyocytes and vascular endothelium. These observations support the
      protective effects of deep hypothermia during I/R. Furthermore, the results
      suggest an increased structural remodelling of the myocardial basement membrane
      with potential functional impairment during mild hypothermic I/R which may
      contribute to the progression to post-ischemic heart failure.

PMID- 24681714
TI  - A qPCR assay to detect and quantify Shiga toxin-producing E. coli (STEC) in
      cattle and on farms: a potential predictive tool for STEC culture-positive farms.
AB  - Shiga toxin-producing E. coli (STEC), of various serogroups harboring the intimin
      gene, form a serious threat to human health. They are asymptomatically carried by
      cattle. In this study, a quantitative real-time PCR (qPCR) method was developed
      as a molecular method to detect and quantify Shiga toxin genes stx1 and stx2 and
      the intimin gene eae. Subsequently, 59 fecal samples from six farms were tested
      using qPCR and a culture method as a reference. Three farms had contaminated
      animals as demonstrated by the culture method. Culture-positive farms showed
      moderate significantly higher stx prevalences than culture-negative farms (p =
      0.05). This is the first study which showed preliminary results that qPCR can
      predict STEC farm contamination, with a specificity of 77% and a sensitivity of
      83%, as compared with the culture method. Furthermore, the presence or quantity
      of stx genes in feces was not correlated to the isolation of STEC from the
      individual animal. Quantitative data thus did not add value to the results.
      Finally, the detection of both stx and eae genes within the same fecal sample or
      farm using qPCR was not correlated with the isolation of an eae-harboring STEC
      strain from the respective sample or farm using the culture method. 

PMID- 24681715
TI  - Cardiopulmonary exercise testing before and after blood transfusion: a
      prospective clinical study.
AB  - BACKGROUND: Cardiopulmonary exercise testing (CPET) is used to risk-stratify
      patients undergoing major elective surgery, with a poor exercise capacity being
      associated with an increased risk of complications and death. Patients with
      anaemia have a decreased exercise capacity and an increased risk of morbidity and
      mortality after major surgery. Blood transfusion is often used to correct anaemia
      in the perioperative period but the effect of this intervention on exercise
      capacity is not well described. We sought to measure the effect of blood
      transfusion on exercise capacity measured objectively with CPET. METHODS:
      Patients with stable haematological conditions requiring blood transfusion
      underwent CPET before and 2-6 days after transfusion. RESULTS: Twenty patients
      were enrolled and completed both pre- and post-transfusion tests. The mean (sd)
      haemoglobin (Hb) concentration increased from 8.3 (1.2) to 11.2 (1.4) g dl(-1)
      after transfusion of a median (range) of 3 (1-4) units of packed red cells. The
      anaerobic threshold increased from a mean (sd) of 10.4 (2.4) to 11.6 (2.5) ml kg(
      1) min(-1) (P=0.018), a mean difference of 1.2 ml kg(-1) min(-1) (95% confidence
      interval (CI)=0.2-2.2). When corrected for the change in Hb concentration, the
      anaerobic threshold increased by a mean (sd) of 0.39 (0.74) ml kg(-1) min(-1) per
      g dl(-1) Hb. CONCLUSIONS: Transfusion of allogeneic packed red cells in anaemic
      adults led to a significant increase in their capacity to exercise. This increase
      was seen in the anaerobic threshold, and other CPET variables.

PMID- 24681716
TI  - Excavation of Pid3 orthologs with differential resistance spectra to Magnaporthe
      oryzae in rice resource.
AB  - Twenty-six orthologs of the rice blast resistance gene Pid3 from cultivated
      varieties and wild rice accessions distributed in different areas were cloned by
      allele mining. Sequence analysis showed that while each of the orthologous genes
      from indica varieties and most wild accessions encodes a complete NBS-LRR
      protein, each of the proteins encoded by those from japonica varieties and few
      wild rice accessions presents a premature termination. Eleven of the 26 orthologs
      were selected for blast resistance testing by transforming into the blast
      susceptible rice variety TP309, respectively. Inoculation of 23 M. oryzae strains
      collected from diverse regions of China to the respective transgenic plants
      revealed that 6 Pid3 orthologs showed susceptible to all the tested strains,
      while the other 5 orthologs showed differential resistance spectra in a gradually
      spectrum-widen order as Pid3-W3, Pid3-W4, Pid3-I3, Pid3-W5 and Pid3-I1. Amino
      acid sequences alignment of these orthologs indicated that the sequence
      diversities between the blast resistance orthologs were mostly located in the LRR
      domain such as the substitutions of Q694H,D856H,Q896R,D899E etc. However, the
      differences between the resistance orthologs and the susceptible ones were mostly
      located in the NBS domain. The present experiments provide an example of that the
      ortholog evaluation of plant R genes could be an efficient way to expand the rice
      blast resistance and some other plant disease resistance as well for breeding. 

PMID- 24681717
TI  - Acceptability of online self-help to people with depression: users' views of
      MoodGYM versus informational websites.
AB  - BACKGROUND: Little is known about the factors that influence acceptability of and
      adherence to online psychological interventions. Evidence is needed to guide
      further development of promising programs. OBJECTIVE: Our goal was to investigate
      users' views of two online approaches to self-help for depression: computerized
      cognitive behavior therapy (cCBT) and informational websites, in a workplace
      context. Computerized CBT offers an inexpensive and accessible alternative to
      face-to-face therapy, and employers have an interest in reducing the working time
      lost to depression or stress. Yet little is known about how employees, who have
      actual experience of using online approaches, judge the intervention as a
      process. METHODS: The qualitative data reported here were collected within an
      online randomized controlled trial whose participants had diagnosable depression.
      The experimental intervention was a 5-week cCBT program called MoodGYM, and the
      control condition was five informational websites about mental health. Data were
      collected via online questionnaires. There was no evidence of the superiority of
      either in terms of treatment outcomes. In parallel, using brief rating scales and
      open-ended questions designed for this purpose, we examined the relative
      acceptability of each approach over time, including perceptions of cCBT compared
      to seeing a health care professional. RESULTS: At least 60% of participants held
      online therapy to be at least as acceptable as seeing a professional about mental
      health issues, and they were more likely to retain this opinion over time if they
      used the interactive program, MoodGYM, rather than informational websites alone.
      Barriers to cCBT use fell into four categories: intrinsic, intrapersonal
      problems; extrinsic technical problems; generic issues mostly pertaining to
      perceptions of cCBT; and specific issues about the intervention or control
      condition. These indicate strategies for improving engagement. CONCLUSIONS: As
      first-aid for mild to moderate mental health problems, evidence-based
      computerized approaches have broad acceptability. This could be increased by
      attending to the barriers noted here and by proactively managing users'
      expectations at individual and organizational levels. The findings have
      implications for occupational health providers and others addressing the needs of
      working-age adults with depression. They also raise methodological issues for
      online research. TRIAL REGISTRATION: International Standard Randomized Controlled
      Trial Number (ISRCTN): 24529487; http://www.controlled-trials.com/ISRCTN24529487
      (Archived by Webcite at http://www.webcitation.org/6O8cCL4mh).

PMID- 24681718
TI  - Reply to: "a fair comparison".

PMID- 24681719
TI  - A fair comparison.

PMID- 24681720
TI  - Single-cell in situ RNA profiling by sequential hybridization.

PMID- 24681721
TI  - MutationTaster2: mutation prediction for the deep-sequencing age.

PMID- 24681722
TI  - Cancer genomes: discerning drivers from passengers.

PMID- 24681723
TI  - Next-gen immunohistochemistry.

PMID- 24681724
TI  - Gold-catalysed cyclisation of N-propargylic beta-enaminones to form 3-methylene-1
      pyrroline derivatives.
AB  - A gold(I) catalysed reaction between N-propargylic beta-enaminones and arynes was
      developed to access 3-methylene-1-pyrrolines. The title compounds were obtained
      in 57-78% yields. This reaction is useful for the generation of substituted 1
      pyrrolines exhibiting significant molecular complexity.

PMID- 24681725
TI  - What is the role of preoperative scintigraphic imaging and the intraoperative
      gamma probe in secondary hyperparathyroidism?

PMID- 24681728
TI  - The surprising lability of bis(2,2':6',2''-terpyridine)chromium(III) complexes.
AB  - The complex [Cr(tpy)(O3SCF3)3] (tpy = 2,2':6',2''-terpyridine) is readily made
      from [Cr(tpy)Cl3] and is a convenient precursor to [Cr(tpy)2][PF6]3 and to
      [Cr(tpy)(4'-(4-tolyl)tpy)][PF6]3 and [Cr(tpy)(5,5''-Me2tpy)][PF6]3 (4'-(4
      tolyl)tpy = 4'-(4-tolyl)-2,2':6',2''-terpyridine; 5,5''-Me2tpy = 5,5''-dimethyl
      2,2':6',2''-terpyridine); these are the first examples of heteroleptic bis(tpy)
      chromium(III) complexes. The single crystal structures of
      2{[Cr(tpy)2][PF6]3}.5MeCN, [Cr(tpy)(4'-(4-tolyl)tpy)][PF6]3.3MeCN and
      [Cr(tpy)(5,5''-Me2tpy)][PF6]3.3MeCN have been determined. Each cation contains
      the expected octahedral {Cr(tpy)2}(3+) unit; in all three structures, the need to
      accommodate three anions per cation and the solvent molecules prevents the
      formation of a grid-like array of cations that is typical of many lattices
      containing {M(tpy)2}(2+) motifs. Three reversible electrochemical processes are
      observed for [Cr(tpy)(4'-(4-tolyl)tpy)][PF6]3 and [Cr(tpy)(5,5''-Me2tpy)][PF6]3,
      consistent with those documented for [Cr(tpy)2](3+). At pH 6.36, aqueous
      solutions of [Cr(tpy)2][PF6]3 are stable for at least two months. However,
      contrary to the expectations of the d(3) Cr(3+) ion being a kinetically inert
      metal centre, the tpy ligands in [Cr(tpy)2](3+) are labile in the presence of
      base; absorption and (1)H NMR spectroscopies have been used to monitor the
      effects of adding NaOH to aqueous and CD3OD solutions, respectively, of the homo-
      and heteroleptic complexes. Ligand dissociation is also observed when [Bu4N]F is
      added to CD3OD solutions of the complexes, but in aqueous solution,
      [Cr(tpy)2][PF6]3 is stable in the presence of fluoride ion.

PMID- 24681727
TI  - MAP4K4 deletion inhibits proliferation and activation of CD4(+) T cell and
      promotes T regulatory cell generation in vitro.
AB  - CD4(+) T cells are critical for adaptive immunity. MAP4K4 is a key member of
      germinal center kinase group. However, the physiological function of MAP4K4 in
      primary CD4(+) T cells is still unclear. In this study, it was demonstrated that
      in vitro, MAP4K4 deletion remarkably suppressed CD4(+) T cell proliferation in
      response to phorbol 12-myristate 13-acetate (PMA) and ionomycin, which was not
      due to enhancing cell apoptosis. Additionally, MAP4K4 was required for the
      activation of CD4(+) T cells. MAP4K4 deletion significantly down-regulated
      expression of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), while
      notably up-regulating the expression of regulatory T cells (Treg) transcription
      factor Foxp3 in peripheral CD4(+) T cells. Furthermore, western blot analysis
      indicated that CD4(+) T cells lacking MAP4K4 failed to phosphorylate Jnk, Erk,
      p38 and PKC-theta. Thus, our results provide the evidence that MAP4K4 is
      essential for CD4(+) T cell proliferation, activation and cytokine production. 

PMID- 24681729
TI  - Multifocal FIGO stage 1A1 cervical squamous carcinomas have an extremely good
      prognosis equivalent to unifocal lesions.
AB  - Early invasive squamous carcinomas of the cervix are sometimes multifocal. There
      are few guidelines regarding how to measure multifocal carcinomas and options
      include measuring from the edge of 1 invasive focus to the edge of the furthest
      invasive focus, adding the maximum horizontal dimension of each invasive focus
      together or regarding multiple foci as representing distinct small areas of
      invasion and if clearly separate measure them individually. For tumors with a
      shallow depth of invasion (<3 mm), this has implications for staging and
      management because if the maximum horizontal dimension is taken from the edge of
      1 invasive focus to the edge of the furthest invasive focus, this could represent
      a International Federation of Gynaecology and Obstetrics (FIGO) 1B1 carcinoma,
      whereas alternatively these could be regarded as separate foci of 1A1 disease. It
      has been our practice to regard such lesions as representing multiple foci of
      invasion (multifocal FIGO 1A1 carcinomas) if clearly separate, arbitrarily
      defined by us as a minimum of 2 mm between each separate focus of invasion. In
      this study, we have obtained follow-up in a series of "multifocal 1A1 cervical
      squamous carcinomas" treated by local excisional methods (large loop excision of
      transformation zone or cone biopsy) with margins clear of premalignant and
      malignant disease. The study included 22 cases, 11 of which (50%) would have been
      regarded as FIGO stage 1B1 if the horizontal dimension had been measured from the
      edge of 1 invasive focus to the edge of the furthest invasive focus. In none of
      the cases was there evidence of recurrence of premalignant or malignant disease
      during follow-up (9-91 mo; mean and median 48 and 45.5 mo, respectively).
      Although limited by a relatively small number of cases, our results support the
      hypothesis that with regard to tumor staging and management, it is best to
      consider multifocal lesions as representing separate individual foci of invasion,
      to measure each focus separately, and to determine the FIGO stage on the basis of
      the highest FIGO stage of an individual focus. 

PMID- 24681730
TI  - Increased EZH2 expression is associated with proliferation and progression of
      cervical cancer and indicates a poor prognosis.
AB  - The objective of this study was to illustrate the role of enhancer zeste homolog
      2 (EZH2) overexpression in the proliferation, progression, and prognosis of
      cervical cancer. We detected EZH2 and Ki-67 expression levels using
      immunohistochemical (IHC) studies in 20 normal cervical tissues, 50 cervical
      intraepithelial neoplasia (including 25 low-grade intraepithelial lesions and 25
      high-grade intraepithelial lesions), and 101 cervical cancer tissues. The
      relationships between EZH2 expression and Ki-67 expression, conventional
      clinicopathologic characteristics of cervical cancer, and patient outcomes were
      evaluated. The effect of EZH2 expression on cancer-specific survival was assessed
      by multivariate Cox regression analysis. Positive expression of EZH2 was detected
      in 10% (2/20) of the normal cervical tissues, 52% (13/25) of the low-grade
      squamous intraepithelial lesions, 64% (16/25) of the high-grade squamous
      intraepithelial lesions, and 68.3% (69/101) of the cervical cancer tissues. The
      expression of Ki-67 was positively correlated with EZH2 expression: 5% (1/20) in
      normal cervical tissues, 48% (12/25) in low-grade squamous intraepithelial
      lesions, 52% (13/25) in high-grade squamous intraepithelial lesions, and 57.4%
      (58/101) in cervical cancer tissues. Overexpression of EZH2 was adversely
      associated with clinical stage, histologic differentiation, infiltration depth,
      and lymph node metastasis (P<0.05). Patients with EZH2-positive expression showed
      a decreased overall survival compared with those with EZH2-negative expression
      (P=0.003, log-rank test). Multivariate Cox regression analysis suggested that
      overexpression of EZH2 was an independent predictor of poor prognosis in cervical
      cancer. Overexpression of EZH2 was closely associated with the carcinogenesis,
      proliferation, clinical and biologic behaviors, and the prognosis of cervical
      cancer, suggesting that it might be used as a potential predictor of prognosis in
      cervical cancer. 

PMID- 24681732
TI  - Acquired vulvar lymphangioma: a case series with emphasis on expanding clinical
      contexts.
AB  - Vulvar lymphangioma circumscriptum (LC) is an unusual benign condition,
      congenital or acquired, related to interference in the lymph drainage. Acquired
      cases are usually related to oncological surgical procedures. We report 6 cases
      of vulvar LC: 3 have been caused by surgery and radiotherapy for gynecologic
      cancer, whereas the other 3 have originated under benign conditions--Crohn
      disease, recurring episodes of cellulits, and lower limb lymphedema. In 3 of
      them, the initial clinical diagnosis was genital wart. Surgical exeresis was
      performed as the treatment of choice in 5 patients and there were 3 cases of
      recurrences. Diagnosis of this unusual condition is not always easy even after
      histopathologic examination. The possibility of vulvar LC should be taken into
      account as a possible diagnosis in patients with previous oncological surgery or
      genital warts refractory to the conventional treatment. In these cases, a biopsy
      of not only the epidermis but also the superficial dermis is recommendable to
      rule out inflammatory or tumoral processes. Knowledge on the features of this
      lesion can avoid unnecessary clinical and therapeutic procedures.

PMID- 24681731
TI  - Cox-2, EGFR, and ERBB-2 expression in cervical intraepithelial neoplasia and
      cervical cancer using an automated imaging system.
AB  - We hypothesized that the activation of cyclooxygenase (COX)-2, epidermal growth
      factor receptor (EGFR), and ErbB-2 signaling is required for cervical
      intraepithelial neoplasia (CIN) lesions to progress to cervical cancer. A
      retrospective analysis was performed in 179 patients with Stage I squamous cell
      carcinoma (SCC) and 233 patients with CIN (112 CIN I, 47 CIN II, and 74 CIN III).
      COX-2, EGFR, and ErbB-2 expression was analyzed by immunohistochemistry using the
      ACIS III automated imaging system. The mean expression of COX-2, EGFR, and ErbB-2
      was compared between the various stages of CIN and SCC. COX-2 mean expression was
      predominantly cytoplasmic, increasing significantly from CIN I to CIN II, CIN
      III, and SCC (P<0.001). EGFR mean expression also rose significantly during tumor
      progression from CIN I to SCC (P=0.001). CIN I samples were negative for ErbB-2
      expression. CIN II, CIN III, and SCC were considered positive for ErbB-2
      expression in 2.2%, 14%, and 16.2% of cases, respectively. There was also a
      statistically significant correlation between increase of ErbB-2 positivity from
      CIN to SCC. We conclude that COX-2, EGFR, and ErbB-2 expression increase
      significantly during the progression of CIN to cancer. 

PMID- 24681733
TI  - The staining patterns of 53BP1 nuclear foci and 53BP1 mRNA level are associated
      with cervical cancer progression and metastasis.
AB  - p53-binding protein 1 (53BP1) plays a key role in DNA damage response mechanism,
      which protects genome integrity and guards against cancer. Although abnormal DNA
      damage response type of 53BP1 nuclear foci (NF) have been indicated to be
      associated with many types of malignancies, how the staining pattern of 53BP1 NF
      and the mRNA level of 53BP1 correlate with the clinicopathologic characteristics
      of cervical cancer is still unclear. In this study, we examined the staining
      pattern and mRNA level of 53BP1 in cervical premalignant and malignant lesions
      and normal cervical tissue by immunofluorescence staining and quantitative real
      time polymerase chain reaction. We found that the level of 53BP1 NF increased in
      the following order: normal cervical tissues, cervical intraepithelial neoplasia
      (CIN) 1, CIN2/3, and cervical cancers, indicating that the level of 53BP1 NF
      increases as cervical cancer initiates and progresses. In addition, we also found
      that abnormal DNA damage response type of 53BP1 NF and low mRNA level of 53BP1
      was significantly correlated with high histologic grade of cervical cancer, and
      low mRNA level of 53BP1 was also significantly associated with positive lymph
      node metastasis of cervical cancer. 

PMID- 24681734
TI  - Colloid carcinoma of the uterine cervix: a case report with respect to
      immunohistochemical analyses.
AB  - Colloid carcinoma, characterized by the presence of a large amount of
      extracellular mucin that results in the formation of mucous lakes with a relative
      paucity of neoplastic glandular cells within them, is extremely rare in the
      uterine cervix. Herein, we report an additional case of colloid carcinoma of the
      cervix and discuss the immunohistochemical characteristics and histogenesis of
      this extremely rare tumor. A 47-year-old Japanese female without any history of
      carcinomas was found to have a bulky mass in the cervix. Biopsy from the cervix
      revealed adenocarcinoma; subsequently, total hysterectomy was performed.
      Histopathologic study demonstrated that columnar or cuboidal neoplastic glandular
      cells forming cribriform or tubular structures floated within the mucous lakes
      involving almost the entire layer of the cervical wall. Adenocarcinoma in situ
      (AIS) component was also observed. Immunohistochemically, tumor cells of the
      colloid carcinoma were positive for cytokeratin 7, MUC5AC, MUC6, and p16
      (diffuse), but negative for cytokeratin 20, MUC2, and cdx-2. In addition, human
      papillomavirus 16 was detected in both colloid carcinoma and AIS components. This
      is the first reported case of endocervical type colloid carcinoma, and the second
      documented case of cervical colloid carcinoma with immunohistochemical analyses
      of mucin. The present case had an endocervical type AIS component, which suggests
      that AIS may be a precursor lesion of colloid carcinoma. Moreover, this case
      clearly demonstrates that the occurrence of cervical colloid carcinoma correlates
      with high-risk human papillomavirus. 

PMID- 24681735
TI  - Infiltrating adenomyosis of the cervix with features of a low-grade stromal
      sarcoma: a case report and a literature review.
AB  - Adenomyosis is a common, non-neoplastic, chronic gynecologic disorder that is
      detected in 5% to 70% of hysterectomy specimens. It is characterized by the
      presence of ectopic endometrial glands and stroma within the myometrium, and it
      occurs mostly in late reproductive age women. Adenomyosis has a propensity to
      present in the uterine fundus and is rarely seen in the cervix. At present, the
      most reliable way to diagnose adenomyosis is by pathologic examination of the
      hysterectomy specimens. Herein, we report a case of infiltrating adenomyosis in
      the cervix with unusual clinical and pathologic findings. 

PMID- 24681736
TI  - Vulval intestinal/enteric heterotopia with a 10-yr follow-up: a case report and
      review of the literature.
AB  - The occurrence of ectopic intestinal/enteric-type epithelium at the vulva is a
      rare entity sometimes mimicking intraepithelial neoplasia or malignant disease.
      Here, we report a case of an 82-yr-old woman with a long-standing (10 yr) white
      papillary lesion with some reddish areas at her left labium, extending into the
      vaginal introitus. Biopsy reports revealed colonic-type glandular epithelium with
      positive immunostaining against CDX-2, p53, CK 7, and CEA, whereas staining
      against estrogen and progesterone receptor, mammoglobin, GCDFP-15, and CK 20 was
      reported to be negative. A follow-up of 10 yr appeared uneventful. The occurrence
      of celomic-type glandular epithelium at the vulva may represent the result of
      dysontogenetic replacement of embryonic stem cells, which undergo mucinous
      differentiation. Thus, the proper diagnostic term may be glandular heterotopia.
      Although some lesions, especially in the proximity to orthotopic vulval glands,
      may be of metaplastic origin. Immunohistochemical staining patterns (CEA, CK 7
      positive, and CK 20 negative) indicate an intestinal/enteric phenotype (i.e.
      intestinal/enteric heterotopia). Because of the reported increased risk of
      malignant transformation of glandular vulval lesions, close clinical follow-up is
      recommended. 

PMID- 24681737
TI  - ASPL-TFE3 translocation in vulvovaginal alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma of the vulvovaginal region is limited to only 8
      reported vaginal cases and 1 vulvar case in the English literature. The
      histogenesis of the tumor remains intriguing with postulates favoring a myogenic
      versus nonmyogenic origin. A reciprocal translocation for ASPL-TFE3 gene fusion,
      frequently detected in ~90% of cases, combined with TFE3 protein immunoexpression
      are highly sensitive and specific methods for diagnostic confirmation. The
      current report describes a unique case of vulvovaginal alveolar soft part sarcoma
      showing the classic morphologic features with documentation of TFE3 protein
      expression and the ASPL-TFE3 gene rearrangement. Furthermore, a brief review of
      the literature of vulvar and vaginal alveolar soft part sarcoma cases with the
      various treatment modalities is outlined. 

PMID- 24681738
TI  - Risk factors for recurrence and prognosis of low-grade endometrial
      adenocarcinoma; vaginal versus other sites.
AB  - Endometrial adenocarcinoma is the most common gynecologic cancer in the United
      States. The prognosis is generally favorable, however, a significant number of
      patients do develop local or distant recurrence. The most common site of
      recurrence is vaginal. Our aim was to better characterize patients with vaginal
      recurrence of low-grade endometrioid adenocarcinoma with respect to associated
      tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO
      Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph
      node dissection. A total of 113 cases with positive lymph nodes or recurrent
      disease were included in our study group. Seventy-three cases (13 Grade 1, 60
      Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2)
      developed vaginal recurrence. We evaluated numerous tumor parameters including:
      percentage myoinvasion, presence of microcystic, elongated, and fragmented
      pattern of myoinvasion, lymphovascular space invasion, and cervical involvement.
      Clinical follow-up showed that 30% (34/113) of all patients with recurrent
      disease died as a result of their disease during our follow-up period, including
      31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal
      recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent
      extravaginal recurrence before death. Vaginal recurrence patients show increased
      cervical involvement by tumor, but lack other risk factors associated with
      recurrent disease at other sites. There were no deaths among patients with
      isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker
      of aggressive tumor biology. 

PMID- 24681740
TI  - Immunohistochemical loss of BRCA1 protein in uterine serous carcinoma.
AB  - Uterine serous carcinoma is a uncommon aggressive variant of endometrial cancer
      whose biologic origin is unclear. Mutations in p53 and BRCA1 genes play a key
      role in ovarian serous carcinogenesis. We investigated whether the loss of BRCA1
      expression plays a similar role in uterine serous carcinoma. Loss of BRCA1
      expression and Wilms tumor 1 (WT-1) overexpression were detected by
      immunohistochemical analysis. Depth of myometrial invasion, the presence of
      precursor lesions or polyps, and clinical parameters (age, history of breast
      cancer, and germline BRCA1 mutation status) were recorded. A total of 27 cases
      were available for evaluation. Three tumors (11.1%, 95% confidence interval, 2%
      29%) showed the loss of BRCA1 expression. Two of these had known germline
      mutation in BRCA1, and the third had not been analyzed. Two of these cases
      expressed WT-1 or showed some morphologic features suggestive of drop metastasis
      from the adnexa, but no case showed detectable serous tubal intraepithelial
      carcinoma or features of an ovarian primary tumor. Overall, 5 women in the group
      had a personal history of breast cancer, and the finding was significantly
      associated with BRCA1 staining (P=0.049). A subset of uterine serous carcinomas
      shows the loss of BRCA1 protein and is associated with germline mutation. 

PMID- 24681741
TI  - Loss of expressions of Dusp6, Sprouty4, and Sef, negative regulators of
      FGF2/ERK1/2 signaling, in the endometrium of women with adenomyosis.
AB  - Dual-specificity phosphatase 6 (Dusp6), Sprouty4, and similar expression to FGF
      (Sef) are negative modulators of FGF2/ERK1/2 signaling. The objective of the
      study was to evaluate the expressions of Dusp6, Sprouty4, and Sef in eutopic
      endometria of patients with adenomyosis. Endometria from 30 women with
      adenomyosis and 29 women without adenomyosis were used in this study. The
      expressions of Dusp6, Sprouty4, and Sef were investigated by immunohistochemical
      analysis. We found that Dusp6, Sprouty4, and Sef expressions were present in
      endometrial epithelial cells of normal endometria and eutopic endometria of
      adenomyosis. Weak immunostainings were noted in stromal cells in both endometria.
      No cyclical change was noted either in normal endometria or in eutopic endometria
      of adenomyosis during menstrual cycle. By immunohistochemical analysis, we found
      that eutopic endometria of adenomyosis showed significantly decreased Dusp6,
      Sprouty4, and Sef expressions compared with normal endometria. By in situ
      hybridization analysis, we found that the mRNA expressions of Dusp6, Sprouty4,
      and Sef were downregulated in eutopic endometria of adenomyosis compared with
      normal endometria. We conclude that downregulation of Dusp6, Sprouty4, and Sef-
      negative modulators of FGF2/ERK1/2 signaling--was present in eutopic endometria
      of adenomyosis, which may play critical roles in the development of adenomyosis.

PMID- 24681742
TI  - Verrucous carcinoma of the endometrium: a rare and challenging diagnosis.
AB  - Verrucous carcinoma of the endometrium is an exceedingly rare disease with only a
      few cases reported in the literature. We describe the case of a 68-year-old
      postmenopausal patient who presented with vaginal discharge. PAP smears were
      repeatedly reported negative and an endometrial curettage 2 years prior to the
      diagnosis only showed fragments of benign squamous epithelium. Because of
      continuous symptoms a hysterectomy was performed and revealed extensive squamous
      metaplasia of the endometrium with focal transition to verrucous carcinoma. This
      case demonstrates that benign appearing squamous epithelium in curettage
      specimens, especially when abundant, is not necessarily ordinary portio
      epithelium. In this setting, the clinical presentation becomes paramount for
      considering a well differentiated squamous carcinoma of the endometrium and
      avoiding diagnostic delay. 

PMID- 24681743
TI  - Stage IIIC ovarian/peritoneal serous carcinoma: a heterogeneous group of patients
      with different prognoses.
AB  - Primary ovarian serous carcinoma patients presenting with regional lymph node
      metastasis without extrapelvic peritoneal metastasis are considered International
      Federation of Gynecology and Obstetrics (FIGO) Stage IIIC. We studied their
      controversial survival compared with patients with extrapelvic peritoneal
      metastasis in same Stage IIIC. We included primary peritoneal carcinoma patients
      with lymph node metastasis to investigate whether primary site of tumor has a
      prognostic role. Charts of patients treated at the MD Anderson Cancer Center in
      Houston, TX; from 1992 to 2010 were reviewed. Primary ovarian serous carcinoma
      patients were grouped into patients with lymph node metastasis without
      extrapelvic involvement (Group 1, n=13) and patients with additional extrapelvic
      peritoneal involvement (Group 2, n=43). Group 3 patients (n=38) were selected
      using similar criteria as Group 2 but with negative lymph nodes. Group 4 patients
      were those with primary peritoneal serous carcinoma with lymph node metastasis
      (n=13). Group 1 patients had statistically significant better overall survival
      compared with the rest of the groups. Overall survival was significantly better
      in Groups 4 versus 2 and Groups 3 versus 2. Primary ovarian serous carcinoma
      patients with lymph node metastasis without extrapelvic peritoneal involvement
      have better survival than those with additional extrapelvic peritoneal
      involvement. Primary peritoneal serous carcinoma patients with lymph node
      metastasis have better survival than those with primary ovarian serous carcinoma
      with peritoneal and lymph node metastasis. Ovarian serous carcinoma patients with
      extrapelvic peritoneal involvement alone have better survival than those with
      extrapelvic peritoneal involvement and lymph node metastasis. These findings
      support the proposition to revise the FIGO staging system, especially for Stage
      IIIC patients, in order to reflect these prognostic differences. 

PMID- 24681744
TI  - Quantitative analysis of gamma-H2AX and p53 nuclear expression levels in ovarian
      and fallopian tube epithelium from risk-reducing salpingo-oophorectomies in BRCA1
      and BRCA2 mutation carriers.
AB  - Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast
      and ovarian cancer. Increased lifetime ovarian cancer risk among BRCA1/BRCA2
      mutation carriers can be substantially decreased by risk-reducing salpingo
      oophorectomy (RRSO), which also provides material for molecular research on early
      pathogenesis of serous ovarian cancer. RRSO studies have suggested fallopian tube
      as a primary site of serous high-grade ovarian cancer. In this study, the nuclear
      expression levels of gamma-H2AX and p53 using immunohistochemical (IHC) study was
      quantitatively assessed in ovarian and fallopian tube epithelium derived from
      RRSOs in 29 BRCA1 and BRCA2 mutation carriers and in 1 patient with a strong
      family history of breast and ovarian cancer but showing an unknown BRCA status.
      Both p53 and gamma-H2AX nuclear staining levels were significantly higher in
      BRCA1/2 mutation-positive fallopian tube epithelium compared with the control
      fallopian tube epithelium (P<0.006 and P=0.011, respectively). Nuclear expression
      levels of p53 and gamma-H2AX were similar between the BRCA1/2 mutation-positive
      ovarian epithelium and controls. Both gamma-H2AX and p53 showed significantly
      higher nuclear expression levels in BRCA1/2 mutation-positive fallopian tube
      epithelium compared with BRCA1/2 mutation-positive ovarian epithelium (P<0.0001
      and P<0.0001, respectively). BRCA1/2 mutation-positive fallopian tube epithelium
      showed a positive correlation between the gamma-H2AX and p53 nuclear expression
      levels (Pearson r=0.508, P=0.003). Our results of quantitative nuclear p53 and
      gamma-H2AX expression levels in ovarian and fallopian tube epithelium derived
      from RRSO in high-risk patients support the previously suggested role of
      fallopian tube epithelium serving as a possible site of initial serous ovarian
      carcinogenesis. 

PMID- 24681745
TI  - Extramedullary hematopoiesis associated with organizing peritoneal hemorrhage: a
      report of 5 cases in patients presenting with primary gynecologic disorders.
AB  - Extramedullary hematopoiesis (EMH) usually occurs in patients with severe anemia
      or myelofibrosis, and involvement of the serous cavities is uncommon. A total of
      5 cases of peritoneal EMH are presented in patients presenting with primary
      gynecologic pathology including endometrial adenosarcoma (n=2), ovarian
      leiomyosarcoma, and ovarian endometrioid adenocarcinoma (each n=1), all of which
      were associated with peritoneal metastases; the remaining patient had a
      hemorrhagic benign ovarian cyst. All cases were associated with organizing
      peritoneal hemorrhage, and EMH was localized to the reactive granulation tissue.
      EMH was not identified within the tumor tissue in the 4 neoplastic cases.
      Erythroid precursors were present in all cases and granulocytic precursors and
      megakaryocytes were identified in two and three cases, respectively. There was no
      evidence of EMH in the corresponding peritoneal fluid cytology preparations
      examined in 4 cases. None of the patients had a significant hematological
      abnormality at the time of presentation or during a mean follow-up period of 35
      mo (range, 2-66 mo). The mechanism of peritoneal EMH in these cases is uncertain
      but most likely related to tissue hemorrhage and repair as described in other
      sites such as dura, myocardium, and synovium. Pathologists should be aware that
      EMH may involve the peritoneum to avoid misinterpretation of the findings,
      particularly in small biopsy or cytology samples. 

PMID- 24681739
TI  - Differential vimentin expression in ovarian and uterine corpus endometrioid
      adenocarcinomas: diagnostic utility in distinguishing double primaries from
      metastatic tumors.
AB  - This study aimed to assess the diagnostic value of vimentin expression in
      differentiating endometrioid adenocarcinoma of primary uterine corpus and ovarian
      origin. Immunohistochemical analyses for the expression of vimentin in tumoral
      epithelial cells were performed on 149 endometrioid adenocarcinomas wherein the
      primary sites were not in question, including whole tissue sections of 27
      carcinomas of uterine corpus origin (and no synchronous ovarian tumor), 7
      carcinomas of ovarian origin (and no synchronous uterine corpus tumor) and a
      tissue microarray (TMA) containing 91 primary uterine corpus and 24 primary
      ovarian carcinomas. We also assessed 15 cases that synchronously involved the
      uterine corpus and ovary, 15 cases of metastasis to organs/tissues other than
      uterine corpus or ovary as well as 7 lymph node metastases. Vimentin was negative
      in 97% (30/31) of primary ovarian carcinomas. In contrast, 82% (97/118) of
      primary uterine corpus carcinomas were vimentin-positive. Vimentin expression was
      discordant in 53% of synchronous tumors. The sensitivity and specificity of
      negative vimentin staining in predicting an ovarian primary were 97% and 82%,
      respectively, whereas parallel values for positive vimentin staining in
      predicting a primary uterine tumor were 82% and 97%, respectively. The pattern of
      vimentin expression in all cases was maintained in their respective regional
      lymph nodes and distant metastases. In conclusion, ovarian and uterine corpus
      endometrioid adenocarcinomas have different patterns of vimentin expression. If
      validated in larger and/or different data sets, these findings may have
      diagnostic value in distinguishing metastatic lesions from double primary tumors
      involving both sites. 

PMID- 24681747
TI  - Investigation of multi-junction solar cells using electrostatic force microscopy
      methods.
AB  - Multi-junction III-V solar cells are designed to have a much broader absorption
      of the solar spectrum than Si-based or single junctions, thus yield the highest
      conversion. The conversion efficiency can be further scaled with sun
      concentration. The ability of high conversion efficiencies makes multi-junction
      prime candidates for fine-tuning explorations aimed at getting closer to the
      theoretical efficiencies. In this paper, we report on electrostatic force
      microscopy (EFM) measurements of the built-in potential of multi-junction III-V
      semiconductor-based solar cells. Kelvin probe force microscopy (KPFM) was
      employed to qualitatively study the width and electrical properties of individual
      junctions, i.e., built-in potential, activity, and thickness of the p-n
      junctions. In addition, the voltage drops across individual solar cell p-n
      junctions were measured using Kelvin probe microscopy under various operation
      conditions: dark; illuminated; short-circuit; and biased. We present a method
      which enables the measurement of a working structure, while focusing on the
      electrical characteristics of an individual junction by virtue of selecting the
      spectral range of the illumination used. We show that these pragmatic studies can
      provide a feedback to improve photovoltaic device design, particularly of
      operation under a current mismatched situation. This new analysis technique
      offers additional insights into behavior of the multi-junction solar cell and
      shows promise for further progress in this field. 

PMID- 24681749
TI  - The bright side of transposons in crop evolution.
AB  - The past decades have revealed an unexpected yet prominent role of so-called
      'junk DNA' in the regulation of gene expression, thereby challenging our view of
      the mechanisms underlying phenotypic evolution. In particular, several mechanisms
      through which transposable elements (TEs) participate in functional genome
      diversity have been depicted, bringing to light the 'TEs bright side'. However,
      the relative contribution of those mechanisms and, more generally, the importance
      of TE-based polymorphisms on past and present phenotypic variation in crops
      species remain poorly understood. Here, we review current knowledge on both
      issues, and discuss how analyses of massively parallel sequencing data combined
      with statistical methodologies and functional validations will help unravelling
      the impact of TEs on crop evolution in a near future. 

PMID- 24681748
TI  - Using the nonhuman primate model of HCMV to guide vaccine development.
AB  - The natural history of human cytomegalovirus (HCMV) is inextricably associated
      with mucosal surfaces. The vast preponderance of primary infections occur
      following mucosal exposure to infectious virions, and the high seroprevalence of
      HCMV throughout the world is due to long-term excretion of HCMV in bodily fluids
      from multiple mucosal sites. Accumulating evidence presents a model where the
      earliest virus-host interactions following infection dictate the long-term
      pattern of infection, alter innate immune responses that skew adaptive responses
      to enable persistence within an immune host, and are essential for reinfection of
      a host with prior immunity. HCMV has evolved a complex repertoire of viral
      functions fine-tuned to manipulate the immune environment both locally at the
      sites of infection and systemically within an infected host. Collectively, viral
      immune modulation represents a significant impediment for an HCMV vaccine. As
      HCMV can disseminate beyond mucosal surfaces to reinfect immune hosts, it may not
      matter whether prior immunity results from prior infection or immunization. A
      better understanding of the earliest virus-hosts interactions at mucosal surfaces
      may identify elements of the viral proteome that are especially susceptible to
      vaccine-mediated disruption and prevent challenge virus from disseminating to
      distal sites, particularly the maternal-fetal interface. 

PMID- 24681750
TI  - Enzymatic characterization of Chlamydomonas reinhardtii glycolate dehydrogenase
      and its nearest proteobacterial homologue.
AB  - Chlamydomonas reinhardtii contains a unique glycolate dehydrogenase (CrGlcDH) for
      glycolate oxidation in photorespiration that is different in structure from the
      GlcDH enzymes of heteroptrophic prokaryotes and the glycolate oxidases of higher
      plants. Here, we purified the recombinantly overexpressed enzyme and
      characterized its enzymatic properties. CrGlcDH uses D-lactate, but not l
      lactate, as an alternative substrate with similar catalytic efficiency compared
      to glycolate. Other short-chain organic acids are only very slowly oxidized. Only
      the artificial electron acceptors DCIP and PMS, but neither flavine mono- or
      dinucleotides nor nicotinamide dinucleotides or cytochrome c, were used as
      electron acceptors by the recombinant enzyme. The enzyme is sensitive to CuSO4
      suggesting function of reactive sulfhydryl groups in catalysis. Accordingly,
      mutational analysis of a putative Fe-S cluster indicated an important function of
      this domain in catalysis. Evolutionary sequence analysis confirmed that CrGlcDH
      belongs to a so far biochemically uncharacterized group of enzymes that is found
      in chlorophytes and some proteobacteria. The most related proteobacterial
      homologue was only active with d-lactate, but not glycolate as a substrate. Our
      results indicate that in the chlorophytes an existing enzyme changed its
      substrate specificity to support photorespiratory glycolate oxidation. 

PMID- 24681751
TI  - Developmental stimuli and stress factors affect expression of ClGLP1, an emerging
      allergen-related gene in Citrus limon.
AB  - Germins and germin-like proteins (GLPs) constitute an ubiquitous family of plant
      proteins that seem to be involved in many developmental and stress related
      processes. A novel GLP cDNA was isolated from Citrus limon and structural
      features and genomic organization were investigated by in silico and Southern
      blots analysis. In lemon, the ClGLP1 encodes a 24.38 kDa which possesses a
      conserved motif of plant GLPs proteins. A phylogetic analysis mapped ClGLP1 as
      belonging to the GER3 subfamily into the GLP1 group of large GLP family. ClGLP1
      was differentially expressed in the various organs and was highest in mature
      fruit. Moreover, expression in the fruit was tissue- and stage-related as well as
      dependent on agricultural practice (organic vs conventional). ClGLP1 transcripts
      increased during the transition from the green (180 days after blooming) to the
      yellow (240 days after blooming) mature fruit and were strongly enhanced in
      yellow mature fruit from organic compared with conventional culture. A sudden and
      systemic increase in ClGLP1 expression level was observed in leaves injured by
      wounding, together with an increase of endogenous H2O2 amount. Notably, an
      enhancement of H202 was observed in fruit peel during transition from green to
      yellow fruit stage. All together our data showed that ClGLP1 expression can be
      modulated in relation to both developmental stimuli and culture practices;
      evidence is also provided that through an oxidase activity this gene could play a
      role in fruit maturation as well as in stress responses. 

PMID- 24681752
TI  - Polyamine-induced nitric oxide generation and its potential requirement for
      peroxide in suspension cells of soybean cotyledon node callus.
AB  - Polyamines (PAs) induce nitric oxide (NO) generation in plant tissues; however,
      their mechanism is still unclear. In the present study, suspension cells of
      soybean cotyledon-node callus were employed. Using a NO-specific fluorescent dye,
      DAF-FM-DA (3-amino, 4-aminomethyl-2', 7'-difluorescein, diacetate), and laser
      confocal scanning microscopy, changes in NO generation induced by exogenous PAs
      were examined. The results of this study showed that NO fluorescence was
      significantly induced above endogenous levels when callus cells were treated with
      0.05 mM PAs. However, putrescine (Put) was the most active PA. The observed NO
      release by PAs was rapid and without an apparent lag phase. The response was
      quenched when the suspension cells were treated with the NO-specific scavenger
      cPTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-1-oxy-3-oxide). When
      0.01 mM l-aminoguanidine (L-AG) was applied prior to the PA treatments, the NO
      fluorescence was diminished, and the inhibition of NO fluorescence was correlated
      with a decrease in diamine oxidase (DAO) activity. When callus cells were
      incubated with 0.1 mM catalase (CAT) and 1.0 mM N'N-dimethylthiourea (DMTU) prior
      to PA application, NO release was significantly reduced. In sum, our data
      provided evidence for PA-induced NO generation in suspension cells of soybean
      cotyledon node callus and demonstrated that peroxide, potentially derived from PA
      oxidative degradation, was involved in NO release induced by PAs. 

PMID- 24681753
TI  - Meta-analysis of infectious agents and depression.
AB  - Depression is a debilitating psychiatric disorder and a growing global public
      health issue. However, the relationships between microbial infections and
      depression remains uncertain. A computerized literature search of Medline, ISI
      Web of Knowledge, PsycINFO, and the Cochrane Library was conducted up to May
      2013, and 6362 studies were initially identified for screening. Case-control
      studies detected biomarker of microorganism were included. Based on inclusion and
      exclusion criteria, 28 studies were finally included to compare the detection of
      16 infectious agents in unipolar depressed patients and healthy controls with a
      positive incident being defined as a positive biochemical marker of microbial
      infection. A customized form was used for data extraction. Pooled analysis
      revealed that the majority of the 16 infectious agents were not significantly
      associated with depression. However, there were statistically significant
      associations between depression and infection with Borna disease virus, herpes
      simplex virus-1, varicella zoster virus, Epstein-Barr virus, and Chlamydophila
      trachomatis. 

PMID- 24681754
TI  - Colocalization of thin-cap fibroatheroma and spotty calcification is a powerful
      predictor of procedure-related myocardial injury after elective coronary stent
      implantation.
AB  - OBJECTIVES: Percutaneous coronary intervention (PCI)-related cardiac enzyme
      elevation is an independent risk factor for adverse clinical outcomes, but
      preprocedural predictors of this complication have not been established. This
      study evaluated the morphological characteristics of culprit lesions by frequency
      domain optical coherence tomography (FD-OCT), and examined their predictive value
      for procedure-related myocardial injury in patients undergoing elective PCI.
      METHODS: Sixty-eight patients treated by FD-OCT-guided elective PCI were studied.
      On the basis of the presence or absence of postprocedural plasma cardiac troponin
      T (cTnT) elevation, patients were divided into elevation (cTnT-E, n=25) and
      nonelevation (cTnT-nonE, n=43) groups. FD-OCT examinations of culprit lesions
      were performed before and after stent implantation, and tissue characteristics
      were evaluated within a 10-mm-long segment of each lesion. RESULTS: Clinical
      parameters were similar between the two groups. Stent length was significantly
      longer in the cTnT-E group than in the cTnT-nonE group. On baseline OCT images,
      thin-cap fibroatheroma and calcium deposition were more frequently observed
      within culprit segments of the cTnT-E group compared with the cTnT-nonE group
      (32.0 vs. 11.6%, P=0.043, and 72.0 vs. 46.5%, P=0.039, respectively). In
      addition, colocalization of these two findings was a powerful predictor of PCI
      related cTnT elevation (odds ratio 8.40, 95% confidence interval 1.65-52.78,
      P<0.01). Further, the predictive value of this colocalization was enhanced when
      the analysis included only spotty calcification (odds ratio 21.00, 95% confidence
      interval 2.65-454.22, P=0.003). CONCLUSION: FD-OCT examination showed that
      colocalization of thin-cap fibroatheroma and spotty calcification was a powerful
      predictor of PCI-related cTnT elevation. FD-OCT is useful for stratifying risk
      during PCI to avoid procedure-related complications.

PMID- 24681755
TI  - Characterizing photoinhibition and photosynthesis in juvenile-red versus mature
      green leaves of Jatropha curcas L.
AB  - The new leaves of Jatropha curcas (L.) appear dark red in colour due to the
      presence of anthocyanin pigments, these leaves subsequently turn green on
      maturity. The aim of the study was to characterize the photosynthetic efficiency
      of the juvenile red and mature green leaves and to understand the possible role
      of anthocyanin pigment in the juvenile leaves of J. curcas. We studied the
      localization of anthocyanin pigment, reflectance properties, diurnal gas-exchange
      performance, carboxylation efficiency and photosynthetic efficiency under
      different light intensities by investigation of the photochemical and non
      photochemical energy dissipation processes related to Photosystem II (PSII) and
      Photosystem I (PSI), of the juvenile and the mature leaves of J. curcas. The JIP
      test analysis of chlorophyll a fluorescence transients and the gas-exchange
      studies revels the low photosynthetic efficiency of red leaves is due to the
      immaturity of the leaf. The low value of quantum yield of non-photochemical
      energy dissipation due to acceptor side limitation, Y (NA) under high light in
      the red leaf, suggests that over-reduction of PSI acceptor side was prevented and
      it results in the accumulation of oxidized P700, which dissipates excess light
      energy harmlessly as heat and thereby alleviate photoinhibition of PSI in case of
      the juvenile red leaves. Further our results of photoinhibition and relaxation on
      exposure of red and green leaves to monochromatic blue light showed that
      effective quantum yield of PSII recovers faster and completely under darkness in
      juvenile red leaves as compared to mature green leaves, supporting the role of
      anthocyanin pigments in protecting both PSII and PSI in the red leaves. 

PMID- 24681756
TI  - Comparative proteomics of Euphorbia kansui Liou milky sap at two different
      developmental stages.
AB  - Euphorbia kansui Liou is a unique traditional Chinese medicinal herb. Its milky
      sap proteins play important roles in laticifer development, synthesis and
      transport of its biologically active substances. A proteomic approach was applied
      to analyze the E. kansui latex proteins related to laticifer development and
      secondary metabolite synthesis by using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and two-dimensional polyacrylamide gel electrophoresis. A total
      of 125 milky sap proteins associated with development of laticifers, disease and
      defense, and general metabolism were identified, and 19 differentially expressed
      proteins at two different developmental stages of laticifers were successfully
      detected. Peroxidase, cytochrome P450 mono-oxygenase superfamily, lipoxygenase,
      and multidrug resistance protein ABC transporter family may be involved in
      laticifer development, secondary metabolite synthesis and transport, and plant
      physiology. 

PMID- 24681757
TI  - A newer conversion equation for the correlation between HbA1c and glycated
      albumin.
AB  - Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as
      glycemic control markers. These markers are influenced by either altered
      hemoglobin metabolism or albumin metabolism. We investigated the correlation
      between HbA1c and GA by collecting only data that had not been affected by the
      turnover of either HbA1c or GA and proposed a novel equation for accurately
      estimating the extrapolated HbA1c (eHbA1c) value based on the GA value. Data sets
      for a total of 2461 occasions were obtained from 731 patients (including non
      diabetes patients) whose HbA1c and GA values were simultaneously measured. Data
      sets obtained from patients undergoing hemodialysis, patients with hematological
      malignancies, pregnancy, chronic liver diseases, hyperthyroidism, steroid
      treatment or a blood transfusion during the past 3 months, or patients without
      albumin, hemoglobin, eGFR, or urinary protein measurements and data sets with an
      eGFR of less than 30 mL/min/1.73 m(2), a hemoglobin level of less than 10 mg/dL,
      an albumin level of below 3.0 g/mL, or a urinary protein level of 3+ were
      excluded. Finally, we selected 284 data sets. We then analyzed these data sets,
      performed a scatter plot to examine the correlation between HbA1c and GA, and
      established an equation describing the resulting correlation. Based on all the
      data points, the resulting equation was HbA1c = 0.216 * GA + 2.978 [R(2) =
      0.5882, P < 0.001]. 

PMID- 24681758
TI  - Protamine-containing insulin but not analog insulin and duration of insulin use
      are risk factors for the production of insulin autoantibodies in insulin-treated
      patients with diabetes mellitus.
AB  - Insulin autoantibodies can be produced by insulin injections but rarely cause
      severe side effects such as glucose instability and insulin allergy. We study the
      characteristics of insulin autoantibody-positive diabetic patients with a medical
      history of insulin therapy using single and multiple (adjusted for age, sex, type
      of diabetes) logistic regression analyses. Associations between insulin
      autoantibodies and age, sex, type of diabetes, HbA1c, and serum creatinine were
      not significant, but the association between insulin autoantibodies and duration
      of insulin use was significant. Unadjusted and adjusted odds ratios were 1.08
      (1.02-1.14) and 1.07 (1.01-1.14), respectively. Unadjusted and adjusted odds
      ratios for protamine-containing insulin were 3.08 (1.49-6.34) and 4.27 (1.90
      9.58), respectively. The adjusted odds ratios for premixed biphasic insulin and
      intermediate-acting insulin were 2.21 (1.03-4.73) and 2.35 (1.01-5.49),
      respectively. Associations between insulin autoantibodies and any insulin analog
      were not significant. These results suggest that protamine-containing insulin and
      duration of insulin use are risk factors for the production of insulin
      autoantibodies. If patients with poorly controlled diabetes have a history of
      protamine-containing insulin therapy over a long time, the appearance of insulin
      autoantibodies should be monitored. 

PMID- 24681760
TI  - Mouse models of anemia of cancer.
AB  - Anemia of cancer (AC) may contribute to cancer-related fatigue and impair quality
      of life. Improved understanding of the pathogenesis of AC could facilitate better
      treatment, but animal models to study AC are lacking. We characterized four
      syngeneic C57BL/6 mouse cancers that cause AC. Mice with two different rapidly
      growing metastatic lung cancers developed the characteristic findings of anemia
      of inflammation (AI), with dramatically different degrees of anemia. Mice with
      rapidly-growing metastatic melanoma also developed a severe anemia by 14 days,
      with hematologic and inflammatory parameters similar to AI. Mice with a slow
      growing peritoneal ovarian cancer developed an iron-deficiency anemia, likely
      secondary to chronically impaired nutrition and bleeding into the peritoneal
      cavity. Of the four models, hepcidin mRNA levels were increased only in the
      milder lung cancer model. Unlike in our model of systemic inflammation induced by
      heat-killed Brucella abortus, ablation of hepcidin in the ovarian cancer and the
      milder lung cancer mouse models did not affect the severity of anemia. Hepcidin
      independent mechanisms play an important role in these murine models of AC. 

PMID- 24681759
TI  - Neospora caninum calcium-dependent protein kinase 1 is an effective drug target
      for neosporosis therapy.
AB  - Despite the enormous economic importance of Neospora caninum related veterinary
      diseases, the number of effective therapeutic agents is relatively small.
      Development of new therapeutic strategies to combat the economic impact of
      neosporosis remains an important scientific endeavor. This study demonstrates
      molecular, structural and phenotypic evidence that N. caninum calcium-dependent
      protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug
      development. Recombinant NcCDPK1 was expressed, purified and screened against a
      select group of bumped kinase inhibitors (BKIs) previously shown to have low
      IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was
      inhibited by low concentrations of BKIs. The three-dimensional structure of
      NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1
      structures demonstrated the structural basis for potency and selectivity. Calcium
      dependent conformational changes in solution as characterized by small-angle X
      ray scattering are consistent with previous structures in low Calcium-state but
      different in the Calcium-bound active state than predicted by X-ray
      crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation
      in vitro. Electron microscopic analysis of N. caninum cells revealed ultra
      structural changes in the presence of BKI compound 1294. BKI compound 1294
      interfered with an early step in Neospora tachyzoite host cell invasion and
      egress. Prolonged incubation in the presence of 1294 interfered produced
      observable interference with viability and replication. Oral dosing of BKI
      compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted
      in a 10-fold reduced cerebral parasite burden compared to untreated control.
      Further experiments are needed to determine the PK, optimal dosage, and duration
      for effective treatment in cattle and dogs, but these data demonstrate proof-of
      concept for BKIs, and 1294 specifically, for therapy of bovine and canine
      neosporosis. 

PMID- 24681761
TI  - Does brief telephone support improve engagement with a web-based weight
      management intervention? Randomized controlled trial.
AB  - BACKGROUND: Recent reviews suggest Web-based interventions are promising
      approaches for weight management but they identify difficulties with suboptimal
      usage. The literature suggests that offering some degree of human support to
      website users may boost usage and outcomes. OBJECTIVE: We disseminated the POWeR
      ("Positive Online Weight Reduction") Web-based weight management intervention in
      a community setting. POWeR consisted of weekly online sessions that emphasized
      self-monitoring, goal-setting, and cognitive/behavioral strategies. Our primary
      outcome was intervention usage and we investigated whether this was enhanced by
      the addition of brief telephone coaching. We also explored group differences in
      short-term self-reported weight loss. METHODS: Participants were recruited using
      a range of methods including targeted mailouts, advertisements in the local
      press, notices on organizational websites, and social media. A total of 786
      adults were randomized at an individual level through an online procedure to (1)
      POWeR only (n=264), (2) POWeR plus coaching (n=247), or (3) a waiting list
      control group (n=275). Those in the POWeR plus coaching arm were contacted at
      approximately 7 and 28 days after randomization for short coaching telephone
      calls aimed at promoting continued usage of the website. Website usage was
      tracked automatically. Weight was assessed by online self-report. RESULTS: Of the
      511 participants allocated to the two intervention groups, the median number of
      POWeR sessions completed was just one (IQR 0-2 for POWeR only, IQR 0-3 for POWeR
      plus coach). Nonetheless, a substantial minority completed at least the core
      three sessions of POWeR: 47 participants (17.8%, 47/264) in the POWeR-only arm
      and 64 participants (25.9%, 64/247) in the POWeR plus coaching arm. Participants
      in the POWeR plus coaching group persisted with the intervention for longer and
      were 1.61 times more likely to complete the core three sessions than the POWeR
      only group (chi(2) 1=4.93; OR 1.61, 95% CI 1.06-2.47; n=511). An intention-to
      treat analysis showed between-group differences in weight loss (F2,782=12.421,
      P<.001). Both intervention groups reported more weight loss than the waiting list
      control group. Weight loss was slightly, but not significantly, greater in the
      POWeR plus coaching group. A large proportion of participants assigned to POWeR
      plus coaching refused phone calls or were not contactable (57.9%, 143/247).
      Exploratory analyses identified health and sociodemographic differences between
      those who did and did not engage in coaching when it was made available to them.
      Users who engaged with coaching used the intervention more and lost more weight
      than those who did not. CONCLUSIONS: In common with most Web-based intervention
      studies, usage of POWeR was suboptimal overall. However, our findings suggest
      that supplementing Web-based weight management with brief human support could
      improve usage and outcomes in those who take it up. TRIAL REGISTRATION:
      International Standard Randomized Controlled Trial Number (ISRCTN): 98176068;
      http://www.controlled-trials.com/ISRCTN98176068 (Archived by WebCite at
      http://www.webcitation.org/6OKRjM2oy).

PMID- 24681763
TI  - Patient-assessed short-term positive response to cardiac resynchronization
      therapy is an independent predictor of long-term mortality.
AB  - AIMS: Cardiac resynchronization therapy (CRT) has a well-documented positive
      effect on mortality and heart failure morbidity. The aim of this study was to
      assess the long-term survival and the predictive value of self-assessed
      functional status on the long-term prognosis of patients treated with CRT
      pacemaker (CRT-P). METHODS AND RESULTS: Data were retrospectively collected from
      medical records of 446 consecutive patients implanted with CRT-P at a large
      volume Swedish tertiary care centre. Primary outcome was all-cause mortality,
      predictive variables were assessed by log-rank test and univariate cox
      regression. Three hundred and nine patients had reliable information available on
      early improvement after implantation and were included in the multivariate
      analyses. The cohort was followed for a median of 79 months and was similar in
      baseline characteristics compared with major controlled trials. During follow-up
      204 patients died, yearly mortality was 11.7%. Early improvement of self-assessed
      functional status was a strong independent predictor of survival [hazard ratio,
      HR 0.59, confidence interval (CI) 0.40-0.87, P = 0.007], together with well-known
      predictors; NYHA III-IV vs I-II (HR 1.66, CI 1.09-2.536, P = 0.018), age (HR
      1.05, CI 1.03-1.08, P < 0.001), male gender (HR 2.0, CI 1.11-3.45, P = 0.021),
      and loop diuretic use (HR 4.41, CI 1.08-18.02). Patients with early improvement
      of self-assessed functional status had better 2-year and 5-year survival (P <
      0.001). CONCLUSIONS: Real-life patient characteristics and predictors of outcome
      compare well with those in published prospective trials. Self-assessed functional
      status is a strong predictor of long-term survival, which may have implications
      for a more active follow-up of patients without spontaneous improvement.

PMID- 24681762
TI  - Is the 12-lead electrocardiogram during antidromic circus movement tachycardia
      helpful in predicting the ablation site in atriofascicular pathways?
AB  - AIMS: Unlike in the Wolff-Parkinson-White syndrome, there has been no systematic
      study on the role of the pre-excitation pattern in predicting the ablation site
      in patients with atriofascicular (AF) pathways. We assessed in a large cohort the
      value of the 12-lead electrocardiogram (ECG) during antidromic tachycardia (ADT)
      to predict the site of ablation. METHODS AND RESULTS: Forty-five patients were
      studied, 23 males (51%), mean age of 27 +/- 12 years with 46 AF pathways and 48
      ADT using the AF pathway for A-V conduction. Inclusion required induction of a
      sustained ADT and successful ablation. Ablation site was assessed during LAO 45
      degrees  projection and clockwise classified as hours in posteroseptal,
      posterolateral, lateral, anterolateral, and anteroseptal tricuspid annulus as
      follows: 05:00-07:00, >07:00-08:00, >08:00-09:00, >09:00-11:00, and >11:00-13:00
      o'clock. The QRS axis was assessed during ADT and classified as normal (>+15
      degrees ), horizontal (+15 degrees  to -30 degrees ), and superior (<-30 degrees
      ). During ADT axis was superior (-57 degrees  +/- 10 degrees ) in 15 (31%),
      horizontal (-11 degrees  +/- 14 degrees ) in 22 (46%), and normal (+45 degrees 
      +/- 16 degrees ) in 11 (23%) patients. The correct ablation site did not differ
      between the different groups of QRS axis. QRS width during ADT was narrower in
      patients with a normal when compared with a horizontal and leftward axis (127 +/-
      14 vs. 145 +/- 12 ms, P < 0.0001), and the V-H interval was shorter (4 +/- 3 ms
      vs. 19 +/- 22 ms, P = 0.03). CONCLUSIONS: There was no correlation between the AF
      pathway ablation site and the QRS axis during ADT. The 12-lead ECG during maximal
      pre-excitation does not predict the proper site of tricuspid annulus ablation in
      patients with A-V conduction over an AF pathway.

PMID- 24681764
TI  - Preparation of an aminopropyl imidazole-modified silica gel as a sorbent for
      solid-phase extraction of carboxylic acid compounds and polycyclic aromatic
      hydrocarbons.
AB  - In this paper, a kind of aminopropyl imidazole-modified silica sorbent was
      synthesized and used as a solid-phase extraction (SPE) sorbent for the
      determination of carboxylic acid compounds and polycyclic aromatic hydrocarbons
      (PAHs). The resultant aminopropyl imidazole-modified silica sorbent was
      characterized by Fourier transform infrared spectroscopy (FT-IR) and elemental
      analysis (EA) to ensure the successful binding of aminopropyl imidazole on the
      surface of silica gel. Then the aminopropyl imidazole-modified silica sorbent
      served as a SPE sorbent for the enrichment of carboxylic acid compounds and PAHs.
      The new sorbent exhibited high extraction efficiency towards the tested compounds
      and the results show that such a sorbent can offer multiple intermolecular
      interactions: electrostatic, pi-pi, and hydrophobic interactions. Several
      parameters affecting the extraction recovery, such as the pH of sample solution,
      the pH of eluent, the solubility of eluent, the volume of eluent, and sample
      loading, were also investigated. Under the optimized conditions, the proposed
      method was applied to the analysis of four carboxylic acid compounds and four
      PAHs in environmental water samples. Good linearities were obtained for all the
      tested compounds with R(2) larger than 0.9903. The limits of detection were found
      to be in the range of 0.0065-0.5 MUg L(-1). The recovery values of spiked river
      water samples were from 63.2% to 112.3% with relative standard deviations (RSDs)
      less than 10.1% (n = 4). 

PMID- 24681765
TI  - Evaluation of delineation of image details in semiconductor PET utilizing the
      normalized mutual information technique.
AB  - OBJECTIVE: PET using semiconductor detectors provides high-quality images of the
      human brain because of its high spatial resolution. To quantitatively evaluate
      the delineation of image details in clinical PET images, we used normalized
      mutual information (NMI) to quantify the similarity with images obtained through
      MRI. NMI is used to evaluate image quality by determining similarity with a
      reference image. The aim of this study was to evaluate quantitatively the
      delineation of image details provided by semiconductor PET. MATERIALS AND
      METHODS: To quantitatively evaluate anatomical delineation in clinical PET
      images, MRI scans of patients were used as T1-weighted images. [(18)F]
      fluorodeoxyglucose ((18)F-FDG) PET brain images were obtained from six patients
      using (a) a Hitachi semiconductor PET scanner and (b) a ECAT HR+ scintillator PET
      scanner. The NMI calculated from the semiconductor PET and MRI was denoted by
      NMIsemic, whereas the NMI calculated from conventional scintillator PET and MRI
      was denoted by NMIconve. The higher the value of NMI, the greater the similarity
      to MRI. RESULTS: NMIsemic ranged from 1.22 to 1.29, whereas NMIconve ranged from
      1.13 to 1.18 (P<0.05). Furthermore, all the NMI values of the semiconductor PET
      were higher than those of the conventional scintillator PET. CONCLUSION:
      Utilizing NMI, we quantitatively evaluated the delineation of image details in
      clinical PET images. The results reveal that semiconductor PET has superior
      anatomical delineation and physical performance compared with conventional
      scintillator PET. This improved delineation of image details makes semiconductor
      PET promising for clinical applications.

PMID- 24681766
TI  - Evaluation of left ventricular myocardial perfusion and function using gated
      SPECT in patients with hypertrophic obstruction cardiomyopathy following
      percutaneous transluminal septal myocardial ablation.
AB  - OBJECTIVE: This study was designed to evaluate the left ventricular myocardial
      perfusion and function in hypertrophic obstruction cardiomyopathy patients
      following percutaneous transluminal septal myocardial ablation (PTSMA) using rest
      single-photon emission computed tomography (SPECT) myocardial perfusion imaging.
      PATIENTS AND METHODS: Thirty-five patients (24 men and 11 women, 48+/-11 years
      old) with hypertrophic obstruction cardiomyopathy underwent rest-gated Tc-MIBI
      SPECT imaging 4+/-10 days before (baseline) and 4.7+/-1.0 days (short-term) and
      15.5+/-8.2 months (mid-term) after PTSMA. Semiquantitative and QGS quantitative
      evaluations of perfusion and function were carried out in 17 left ventricular
      segments. RESULTS: Myocardial perfusion of the septum following PTSMA was
      significantly reduced compared with baseline in all patients (P<0.05), but the
      myocardial perfusion in the basal septum was significantly higher at mid-term
      compared with short-term following PTSMA (P<0.05). Left ventricular ejection
      fraction was significantly decreased following PTSMA (P<0.05). Regional wall
      motion assessed in the basal anterior, basal septum, and basal inferior areas
      following PTSMA was significantly reduced compared with baseline (P<0.05), and
      wall thickening of the interventricular septum was decreased following PTSMA
      (P<0.05). CONCLUSION: Rest-gated SPECT imaging can be used to assess left
      ventricular myocardial perfusion and function and to investigate the efficacy of
      PTSMA during follow-up.

PMID- 24681767
TI  - Does CEA and CA 19-9 combined increase the likelihood of 18F-FDG in detecting
      recurrence in colorectal patients with negative CeCT?
AB  - AIM: The purpose of this prospective study was to investigate the role of 2
      (fluorine-18)-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/computed tomography (CT)
      in the diagnosis of recurrent colorectal cancer (CRC) in patients with increased
      tumor markers and negative contrast-enhanced computed tomography (CeCT) results.
      MATERIAL AND METHODS: Forty-three patients (27 male; median age 66 years, range
      31-93 years) with increasing tumor markers and negative CeCT during follow-up for
      treated CRC underwent (18)F-FDG PET/CT examinations. The serum values of
      carcinoembryonic antigen (CEA) (n=29) and CA 19-9 (n=20) were normal after
      completion of treatment, with subsequent increasing concentrations. RESULTS:
      Among the 43 patients, (18)F-FDG PET/CT was true positive in 32 (74.4%), false
      positive in two (4.7%), false negative in one (2.3%), and true negative in eight
      (1%) patients. On the patient-basis analysis, (18)F-FDG PET/CT had a sensitivity
      of 97% (confidence interval: 0.82-0.99), a specificity of 80% (0.44-0.96), a
      positive predictive value of 94% (0.78-0.98), and a negative predictive value of
      88% (0.5-0.99). There was no statistically significant correlation between CRC
      recurrence and CEA and CA19-9 levels (P=0.561 and 0.55, respectively). Only in
      the group of patients (n=6) with both tumor markers increased did (18)F-FDG
      PET/CT have 100% accuracy in revealing recurrent disease. CONCLUSION: (18)F-FDG
      PET/CT is highly sensitive in the diagnosis of recurrent CRC in patients with
      increasing levels of tumor markers and negative CeCT regardless of the type or
      level of tumor marker; however, the combination of elevated CEA and CA 19-9
      increases the likelihood of (18)F-FDG in detecting recurrence.

PMID- 24681768
TI  - A sensitive, rapid and inexpensive method to assess aluminium(III) ions in
      technetium eluates.
AB  - The aim of the study was to validate a semiquantitative analytical method to
      identify the aluminium(III) [Al(III)] concentration in 99Mo/99mTc generator
      eluates to check the European Pharmacopoeia (Ph. Eur.) requirement (<5 MUg/ml).
      Three different solutions measuring 20 ml - 0.2% 1,10-phenanthroline, 0.05%
      chrome azurol S and 20% hexamethylenetetramine - were prepared. A cellulose
      filter paper was subsequently immersed in them, dried overnight at room
      temperature and cut into rectangles. A volume of 5 MUl of first eluates of
      various 99Mo/99mTc generators was placed onto a reagent paper and the spot colour
      was compared with a standard aluminium solutions scale (0-100 MUg/ml). A
      cyan/magenta/yellow/key (CMYK) model analysis was adapted to quantify the
      intensity of colour on the paper, and the presence of aluminium in the eluates
      was detected by a spectrophotometer. Small changes in standard solution pH (4.1
      5.2) and chrome azurol S concentration did not affect the analysis. The cyan
      channel image analysis was proportional to the Al3+ solution concentration (y=25
      019x+1489, R2=0.9554 within 2.5-8 MUg/ml). The detection limit for aluminium by
      the visual test method is about 1 MUg/ml, and fading is absent. The cyan channel
      image analysis method is independent of the observer and is applicable for the
      evaluation of the chemical purity of 99Mo/99mTc generator eluates. Our
      colorimetric 'spot test' is advantageous for the visual evaluation of Al
      pertechnetate concentrations as required by Ph. Eur. showing a sensitivity and a
      limit of detection superior to that of commercially available spot systems.

PMID- 24681769
TI  - Exploring the utility of analogies in motor learning after stroke: a feasibility
      study.
AB  - Individuals who have experienced a stroke need to (re)learn motor skills. Analogy
      learning has been shown to facilitate motor learning in sports and may also be an
      attractive alternative to traditional approaches in therapy. The aim of this
      study was to assess the feasibility and utility of analogies to improve the
      walking performance in long-term stroke survivors. Three men aged 76, 87 and 70
      years who were 6, 1 and 3 years poststroke, respectively, presented with
      different walking deficits. An analogy, targeted at improving the walking
      performance was designed with the help of each participant. During a 3-week
      intervention period, the analogy was practiced once weekly under supervision and
      daily at home. To assess feasibility, a structured interview was conducted at the
      end of the intervention period. To assess utility, walking performance was
      assessed using the 10-Metre Walking Test. All three participants were supportive
      of the feasibility and benefits of analogy learning. Two of the participants had
      a meaningful improvement on the 10-Metre Walking Test (0.1 and 0.3 m/s). The
      third participant did not improve most likely because of medication issues during
      the week of the retest. Developing analogies in therapy is a creative and
      challenging process, as analogies must not only guide the correct movement
      pattern, but also be meaningful to the individual. However, as participants were
      supportive of the use of analogies, and positive trends were seen in walking
      speed it seems worthwhile to pursue the use of analogies in future research. 

PMID- 24681770
TI  - Stroke patients after neurological inpatient rehabilitation: a prospective study
      to determine whether functional status or health-related quality of life predict
      living at home 2.5 years after discharge.
AB  - We carried out a prospective study to determine whether stroke patients'
      functional status or health-related quality of life would predict whether they
      lived at home 2.5 years after discharge from neurological inpatient
      rehabilitation. We carried out a single-center prospective cohort study. The
      outcome 'home care' versus 'death' or 'institutionalization' (nursing home
      admission) was evaluated 30 months after discharge. A total of 204 stroke
      survivors with remaining moderate to severe functional deficits at admission to
      neurological inpatient rehabilitation were included. Clinical data were obtained
      at admission to and/or discharge from inpatient rehabilitation. Functional status
      was determined using the Barthel Index; health-related quality of life was
      assessed using the SF-36 and EQ-5D. The outcome was assessed by telephone
      interview. Predictors of living at home were calculated using binary logistic
      regression analysis. In total, 30 months after discharge, 75% of the stroke
      survivors were still living at home. Multivariate analysis showed that patients
      continued to live at home significantly more frequently when they had fewer
      mortality-relevant comorbidities (P=0.001), a higher BMI (P=0.040), a higher
      increase in functional independence during inpatient rehabilitation (P=0.017),
      and above all, a better health-related quality of life, measured using the EQ-5D
      (P<0.001), at discharge. Stroke survivors' health-related quality of life
      measured with the EQ-5D and the change in functional status during multimodal
      neurological rehabilitation appear to be the strongest clinically relevant long
      term predictors of staying at home. 

PMID- 24681771
TI  - Acute pediatric septic arthritis: a systematic review of literature and current
      controversies.
AB  - We present a review of the current literature and the author's opinion regarding
      Septic arthritis in the pediatric age group. The etiopathogenesis, clinical
      features, the laboratory parameters for diagnosis and monitoring of treatment,
      radiological features, are discussed along-with the debatable issues pertaining
      to the choice of antibiotics, their duration, and the need and mode of surgical
      drainage and mobilization of the joint.

PMID- 24681772
TI  - BHATTACHARYYA MEDIAN OF SYMMETRIC POSITIVE-DEFINITE MATRICES AND APPLICATION TO
      THE DENOISING OF DIFFUSION-TENSOR FIELDS.
AB  - In this paper, we present algorithms for the computation of the median of a set
      of symmetric positive-definite matrices using different distances/divergences.
      The novelty of this paper lies in the median computation using the Bhattacharya
      distance on diffusion tensors. The numerical computation of the median is
      achieved using the gradient descent algorithm and the fixed point algorithm. We
      present an application namely, one of denoising tensor-valued data using median
      filters constructed using several distance/divergences and compare their
      performance.

PMID- 24681773
TI  - The use of localised orbitals for the bonding and mechanistic analysis of
      organometallic compounds.
AB  - Through a series of examples we show how, upon orbital localisation, the outcome
      of an electronic structure calculation reveals features, such as bonding and
      oxidation states, which are controversial to grasp by alternative methods. The
      approach can also be applied to the analysis of reaction mechanisms. Because of
      the insight it provides in a limited execution time, we believe that this
      approach, known since the early developments of computational quantum chemistry,
      could find wider applications in the organometallic community than it actually
      has and facilitate communication between computational and experimental chemists.

PMID- 24681774
TI  - Anti-inflammatory and antioxidant effects of Aloe saponaria Haw in a model of UVB
      induced paw sunburn in rats.
AB  - Ultraviolet B (UVB) irradiation mainly affects biological tissues by inducing an
      increase in reactive oxygen species (ROS) production which leads to deleterious
      outcomes for the skin, including pain and inflammation. As a protective strategy,
      many studies have focused on the use of natural products. The aim of this study
      was to investigate the effects of Aloe saponaria on nociceptive, inflammatory,
      and oxidative parameters in a model of UVB-induced sunburn in adult male Wistar
      rats. Sunburned animals were topically treated with vehicle (base cream), 1%
      silver sulfadiazine (positive control) or A. saponaria (10%) once a day for
      6days. UVB-induced nociception (allodynia and hyperalgesia), inflammation (edema
      and leukocyte infiltration) and oxidative stress (increases in H2O2, protein
      carbonyl levels and lipid peroxidation and a decrease in non protein thiol
      content) were reduced by both A. saponaria and sulfadiazine topical treatment.
      Furthermore, A. saponaria or its constituents aloin and rutin reduced the
      oxidative stress induced by H2O2 in skin homogenates in vitro. Our results
      demonstrate that topical A. saponaria treatment displayed anti-nociceptive and
      anti-inflammatory effects in a UVB-induced sunburn model, and these effects seem
      to be related to its antioxidant components. 

PMID- 24681775
TI  - Dynamic relaxation of a levitated nanoparticle from a non-equilibrium steady
      state.
AB  - Fluctuation theorems are a generalization of thermodynamics on small scales and
      provide the tools to characterize the fluctuations of thermodynamic quantities in
      non-equilibrium nanoscale systems. They are particularly important for
      understanding irreversibility and the second law in fundamental chemical and
      biological processes that are actively driven, thus operating far from thermal
      equilibrium. Here, we apply the framework of fluctuation theorems to investigate
      the important case of a system relaxing from a non-equilibrium state towards
      equilibrium. Using a vacuum-trapped nanoparticle, we demonstrate experimentally
      the validity of a fluctuation theorem for the relative entropy change occurring
      during relaxation from a non-equilibrium steady state. The platform established
      here allows non-equilibrium fluctuation theorems to be studied experimentally for
      arbitrary steady states and can be extended to investigate quantum fluctuation
      theorems as well as systems that do not obey detailed balance. 

PMID- 24681776
TI  - Multifunctional wearable devices for diagnosis and therapy of movement disorders.
AB  - Wearable systems that monitor muscle activity, store data and deliver feedback
      therapy are the next frontier in personalized medicine and healthcare. However,
      technical challenges, such as the fabrication of high-performance, energy
      efficient sensors and memory modules that are in intimate mechanical contact with
      soft tissues, in conjunction with controlled delivery of therapeutic agents,
      limit the wide-scale adoption of such systems. Here, we describe materials,
      mechanics and designs for multifunctional, wearable-on-the-skin systems that
      address these challenges via monolithic integration of nanomembranes fabricated
      with a top-down approach, nanoparticles assembled by bottom-up methods, and
      stretchable electronics on a tissue-like polymeric substrate. Representative
      examples of such systems include physiological sensors, non-volatile memory and
      drug-release actuators. Quantitative analyses of the electronics, mechanics, heat
      transfer and drug-diffusion characteristics validate the operation of individual
      components, thereby enabling system-level multifunctionalities. 

PMID- 24681777
TI  - Electronic control of optical Anderson localization modes.
AB  - Anderson localization of light has been demonstrated in a few different
      dielectric materials and lithographically fabricated structures. However, such
      localization is difficult to control, and requires strong magnetic fields or
      nonlinear optical effects, and electronic control has not been demonstrated.
      Here, we show control of optical Anderson localization using charge carriers
      injected into more than 100 submicrometre-scale p-n diodes. The diodes are
      embedded into the cross-section of the optical waveguide and are fabricated with
      a technology compatible with the current electronics industry. Large variations
      in the output signal, exceeding a factor of 100, were measured with 1 V and a
      control current of 1 mA. The transverse footprint of our device is only 0.125
      um(2), about five orders of magnitude smaller than optical two-dimensional
      lattices. Whereas all-electronic localization has a narrow usable bandwidth,
      electronically controlled optical localization can access more than a gigahertz
      of bandwidth and creates new possibilities for controlling localization at
      radiofrequencies, which can benefit applications such as random lasers, optical
      limiters, imagers, quantum optics and measurement devices.

PMID- 24681779
TI  - Gene identification of potential malignant parathyroid tumors phenotype in
      Chinese population.
AB  - Parathyroid carcinoma is a rare tumor associated with poor prognosis, thus early
      preoperative recognition and surgical resection are critical. However, because of
      a lack of definitive diagnostic markers and typical clinical features, it is
      difficult to diagnose this disease in its early stages and it is often
      misdiagnosed as parathyroid adenoma. Additionally, little is known about the
      molecular pathogenesis of parathyroid carcinoma because of its rarity. To better
      understand the molecular genetics of parathyroid carcinoma in the Chinese
      population, we undertook gene expression profiling of eight parathyroid tumors
      (five parathyroid adenomas and three parathyroid carcinomas) and five normal
      parathyroid samples. Differential gene sets between the groups were identified,
      which may serve as diagnostic biomarkers. Using both gene and protein expression,
      we demonstrated that CD24, HMOX1, VCAM1 and KCNA3 are useful markers for
      parathyroid carcinoma. Our findings provide insights into the molecular
      mechanisms of parathyroid tumorigenesis and may help to improve the diagnosis and
      treatment of parathyroid carcinoma. 

PMID- 24681780
TI  - The endocrine role between beta cells and intra-islet endothelial cells.
AB  - The islets of Langerhans is the endocrine function region of pancreas, which
      exist in five cell types. The majority of endocrine cells are insulin-secreting
      beta cells, mixed up with glucagon-secreting alpha-cells. The islets of
      Langerhans are highly vascularized, and the capillary network around the islet is
      about five times denser than that in the exocrine tissues. It guarantees
      endocrine cells adequately contact with the capillary networks. Above mentioned
      is the basis of deep study the interaction between beta cells and capillary.
      Increasing number of studies contribute to the consensus that endothelial cells
      have positive effects in the islet microenvironment. Endothelial cells can act as
      endocrine cells which release many active substances, such as hepatocyte growth
      factors (HGF), thrombospondin-1(TSP-1), laminins, and collagens by means of
      different molecule pathways, inducing beta cells differentiation, proliferation,
      survivor, and insulin release next to the vessels. Apart from the effect of
      endothelial cells on beta cells by paracrine fashion, the islets can utilize VEGF
      A, angiopoietin-1 and insulin signaling to increase the interaction with
      endothelial cells. As the endocrine role of endothelial cells to beta cells, it
      may be a novel target to stimulate beta cells regeneration, promote
      vascularization post islet transplantation strategy in the treatment of diabetes
      mellitus. 

PMID- 24681781
TI  - Nitrogen-incorporated ultrananocrystalline diamond and multi-layer-graphene-like
      hybrid carbon films.
AB  - Nitrogen-incorporated ultrananocrystalline diamond (N-UNCD) and multi-layer
      graphene-like hybrid carbon films have been synthesized by microwave plasma
      enhanced chemical vapor deposition (MPECVD) on oxidized silicon which is pre
      seeded with diamond nanoparticles. MPECVD of N-UNCD on nanodiamond seeds produces
      a base layer, from which carbon structures nucleate and grow perpendicularly to
      form standing carbon platelets. High-resolution transmission electron microscopy
      and Raman scattering measurements reveal that these carbon platelets are
      comprised of ultrananocrystalline diamond embedded in multilayer-graphene-like
      carbon structures. The hybrid carbon films are of low electrical resistivity.
      UNCD grains in the N-UNCD base layer and the hybrid carbon platelets serve as
      high-density diamond nuclei for the deposition of an electrically insulating UNCD
      film on it. Biocompatible carbon-based heaters made of low-resistivity hybrid
      carbon heaters encapsulated by insulating UNCD for possible electrosurgical
      applications have been demonstrated. 

PMID- 24681778
TI  - High thermal conductivity of chain-oriented amorphous polythiophene.
AB  - Polymers are usually considered thermal insulators, because the amorphous
      arrangement of the molecular chains reduces the mean free path of heat-conducting
      phonons. The most common method to increase thermal conductivity is to draw
      polymeric fibres, which increases chain alignment and crystallinity, but creates
      a material that currently has limited thermal applications. Here we show that
      pure polythiophene nanofibres can have a thermal conductivity up to ~ 4.4 W m(-1)
      K(-1) (more than 20 times higher than the bulk polymer value) while remaining
      amorphous. This enhancement results from significant molecular chain orientation
      along the fibre axis that is obtained during electropolymerization using
      nanoscale templates. Thermal conductivity data suggest that, unlike in drawn
      crystalline fibres, in our fibres the dominant phonon-scattering process at room
      temperature is still related to structural disorder. Using vertically aligned
      arrays of nanofibres, we demonstrate effective heat transfer at critical contacts
      in electronic devices operating under high-power conditions at 200  degrees C
      over numerous cycles.

PMID- 24681782
TI  - Alcohol disinhibition of behaviors in C. elegans.
AB  - Alcohol has a wide variety of effects on physiology and behavior. One of the most
      well-recognized behavioral effects is disinhibition, where behaviors that are
      normally suppressed are displayed following intoxication. A large body of
      evidence has shown that alcohol-induced disinhibition in humans affects
      attention, verbal, sexual, and locomotor behaviors. Similar behavioral
      disinhibition is also seen in many animal models of ethanol response, from
      invertebrates to mammals and primates. Here we describe several examples of
      disinhibition in the nematode C. elegans. The nematode displays distinct
      behavioral states associated with locomotion (crawling on land and swimming in
      water) that are mediated by dopamine. On land, animals crawl and feed freely, but
      these behaviors are inhibited in water. We found that additional behaviors,
      including a variety of escape responses are also inhibited in water. Whereas
      alcohol non-specifically impaired locomotion, feeding, and escape responses in
      worms on land, alcohol specifically disinhibited these behaviors in worms
      immersed in water. Loss of dopamine signaling relieved disinhibition of feeding
      behavior, while loss of the D1-like dopamine receptor DOP-4 impaired the ethanol
      induced disinhibition of crawling. The powerful genetics and simple nervous
      system of C. elegans may help uncover conserved molecular mechanisms that
      underlie alcohol-induced disinhibition of behaviors in higher animals. 

PMID- 24681783
TI  - Basal body proteins regulate Notch signaling through endosomal trafficking.
AB  - Proteins associated with primary cilia and basal bodies mediate numerous
      signaling pathways, but little is known about their role in Notch signaling.
      Here, we report that loss of the Bardet-Biedl syndrome proteins BBS1 or BBS4
      produces increased Notch-directed transcription in a zebrafish reporter line and
      in human cell lines. Pathway overactivation is accompanied by reduced
      localization of Notch receptor at both the plasma membrane and the cilium. In
      Drosophila mutants, overactivation of Notch can result from receptor accumulation
      in endosomes, and recent studies implicate ciliary proteins in endosomal
      trafficking, suggesting a possible mechanism by which overactivation occurs in
      BBS mutants. Consistent with this, we observe genetic interaction of BBS1 and
      BBS4 with the endosomal sorting complexes required for transport (ESCRT) gene
      TSG101 and accumulation of receptor in late endosomes, reduced endosomal
      recycling and reduced receptor degradation in lysosomes. We observe similar
      defects with disruption of BBS3. Loss of another basal body protein, ALMS1, also
      enhances Notch activation and the accumulation of receptor in late endosomes, but
      does not disrupt recycling. These findings suggest a role for these proteins in
      the regulation of Notch through endosomal trafficking of the receptor. 

PMID- 24681785
TI  - Coumarins, a class of drugs with a unique contribution to medicine: the tale of
      their discovery.

PMID- 24681784
TI  - GEF-H1 functions in apical constriction and cell intercalations and is essential
      for vertebrate neural tube closure.
AB  - Rho family GTPases regulate many morphogenetic processes during vertebrate
      development including neural tube closure. Here we report a function for GEF
      H1/Lfc/ArhGEF2, a RhoA-specific guanine nucleotide exchange factor that functions
      in neurulation in Xenopus embryos. Morpholino-mediated depletion of GEF-H1
      resulted in severe neural tube defects, which were rescued by GEF-H1 RNA. Lineage
      tracing of GEF-H1 morphants at different developmental stages revealed abnormal
      cell intercalation and apical constriction, suggesting that GEF-H1 regulates
      these cell behaviors. Molecular marker analysis documented defects in myosin II
      light chain (MLC) phosphorylation, Rab11 and F-actin accumulation in GEF-H1
      depleted cells. In gain-of-function studies, overexpressed GEF-H1 induced Rho
      associated kinase-dependent ectopic apical constriction - marked by apical
      accumulation of phosphorylated MLC, gamma-tubulin and F-actin in superficial
      ectoderm - and stimulated apical protrusive activity of deep ectoderm cells.
      Taken together, our observations newly identify functions of GEF-H1 in
      morphogenetic movements that lead to neural tube closure. 

PMID- 24681786
TI  - Risk factors clustering within the metabolic syndrome: a pattern or by chance?
AB  - INTRODUCTION: An accumulation of various cardiovascular risk factors has been
      noted to occur within the clinical diagnosis of metabolic syndrome. However, it
      remains unclear whether specific risk factors aggregate following a predefined
      pattern or whether this happens by chance. METHODS: This cross-sectional study
      involved 1715 adults, 37% males and 63% females, aged 34-80 years, who were
      consecutively recruited from cardiology and endocrinology outpatient clinics, and
      from internal medicine specialists in the primary healthcare physician office
      setting in Serbia, on a one-third basis. According to the AHA/NHLBI criteria, the
      actual prevalence of a combination of 3 or more of the following risk factors was
      determined: abnormal waist circumference, hypertension, high triglycerides, low
      high-density lipoprotein cholesterol, and abnormal fasting glucose. In addition,
      the prevalence of a corresponding combination of 3 factors was predicted from the
      prevalence of each factor in a given population, assuming that their combination
      occurred as the result of chance. RESULTS: The most frequent risk factor was
      hypertension (87%), followed by waist circumference (60%), dyslipidemia (55%),
      and abnormal fasting glucose level (50%). Metabolic syndrome was identified in
      1135 participants (66.2%). The actual prevalence of the combination of increased
      waist circumference, elevated blood sugar and hypertension was found to be 5
      times more frequent than would be expected to occur by chance (10% actual vs. 2%
      predicted; p<0.0001). CONCLUSIONS: A predefined aggregation pattern of risk
      factors within the metabolic syndrome was found for abdominal obesity, abnormal
      fasting glucose and hypertension. These risk factors do cluster more frequently
      than coincidental phenomena in the subjects of the given population, implying
      common underlying pathophysiological mechanisms.

PMID- 24681787
TI  - H2O2 evokes injury of cardiomyocytes through upregulating HMGB1.
AB  - INTRODUCTION: Reactive oxygen species (ROS) have been shown to induce cell
      apoptosis in cardiomyocytes. However, the underlying mechanism remains unclear.
      This study aimed to investigate the role of high-mobility group box 1 protein
      (HMGB1) in cardiomyocytes undergoing H2O2 treatment. METHODS: Neonatal rat
      cardiomyocytes were treated with H2O2 (100, 200, 500 uM) or pre-treated with
      antioxidant N-acetylcysteine (NAC 200 uM) or HMGB1 neutralizing antibody (20
      ug/ml) in an appropriate concentration of H2O2 (200 uM). The cell viability,
      apoptosis rate, lactate dehydrogenase (LDH), and the activity of superoxide
      dismutase were measured. HMGB1 expression was assessed by immunoblotting.
      RESULTS: H2O2-induced ROS significantly decreased cell viability, promoted the
      apoptosis of neonatal myocytes, and upregulated the expression of HMGB1 in a dose
      dependent manner. However, NAC or HMGB1 neutralizing antibody suppressed the loss
      of cell viability and the rate of cell apoptosis induced by H2O2. NAC or HMGB1
      neutralizing antibody also significantly suppressed the release of LDH and the
      expression of HMGB1. CONCLUSION: The present study suggests that H2O2-induced ROS
      evoke injury to cardiomyocytes that may be associated with upregulating HMGB1.

PMID- 24681788
TI  - How to measure the right ventricular outflow tract with cardiovascular magnetic
      resonance imaging: a head-to-head comparison of methods.
AB  - INTRODUCTION: Structural abnormalities of the right ventricular outflow tract
      (RVOT) have been described in several clinical conditions. The aim of our study
      was to prospectively compare the available approaches to measuring the RVOT area
      and diameter by cardiovascular magnetic resonance imaging (CMR) and establish
      reference values in healthy volunteers. In addition, we sought to introduce a new
      algorithm for dedicated RVOT area evaluation determined by the RVOT axis.
      METHODS: In 50 healthy volunteers CMR was performed to measure the RVOT area: 1)
      on axial images using turbo spin echo imaging (axial TSE), 2) on steady state
      free precession (axial SSFP), 3) on short axis slices using SSFP (SAX SSFP), and
      4) on a plane determined by the RVOT axis using SSFP (RVOT axis SSFP).
      Additionally, the RVOT diameter was measured on SSFP SAX images. RESULTS: RVOT
      measurements on axial TSE (8.4 +/- 1.4 cm(2)) and on RVOT axis SSFP images were
      comparable (8.4 +/- 0.1 cm(2), p=0.99). The axial SSFP (10.2 +/- 1.5 cm(2)) and
      SAX SSFP (11.0 +/- 1.9 cm(2)) images resulted in significantly larger RVOT areas
      than on the axial TSE images (p<0.0001) and on the RVOT axis SSFP images
      (p<0.0001). The RVOT diameter measured was 22.4 +/- 0.3 mm. RVOT assessment on
      the axial SSFP and RVOT axis SSFP images revealed the best intra- and
      interobserver reliability. CONCLUSION: RVOT area measurements differ
      significantly in healthy volunteers, depending on the imaging plane and
      technique. In view of the excellent intra- and interobserver reliability and the
      precise image plane positioning, we recommend the new RVOT axis approach for
      dedicated RVOT measurements.

PMID- 24681789
TI  - Early cardiac gene transcript levels in peripheral blood mononuclear cells
      reflect severity in stable coronary artery disease.
AB  - INTRODUCTION: The early cardiac marker genes myocardin, GATA4 and Nkx2.5, play a
      role in both embryonic cardiovascular development and adult cardiovascular
      disease. We evaluated transcript levels of myocardin, GATA4 and Nkx2.5 in
      peripheral blood mononuclear cells (PBMCs) in patients with stable coronary
      artery disease (CAD) and we examined the relationship between these levels and
      the severity of the disease, estimated by the number of stenotic vessels
      involved. METHODS: Ninety-eight patients with stable CAD (age 66 +/- 9 years) who
      underwent coronary angiography participated in the study; 66 healthy individuals
      (age 58 +/- 13 years) were also included for comparison. Gene transcript levels
      were determined by quantitative real-time reverse transcription polymerase chain
      reaction. RESULTS: Patients with 3-vessel CAD had elevated transcript levels of
      myocardin (median difference 2.7, p=0.001, 95% confidence interval, CI: 1-5.8),
      GATA4 (median difference 0.3, p=0.015, 95% CI: 0.1-1.9) and Nkx2.5 (median
      difference 16.1, p<0.001, 95% CI: 4.5-23) compared to healthy controls. Patients
      with 3-vessel CAD also showed elevated transcript levels of myocardin (median
      difference 2.3, p=0.001, 95% CI: 0.49-5.5) and Nkx2.5 (median difference 11.8,
      p<0.001, 95% CI: 1.5-21.5) compared to patients with 1-vessel CAD. CONCLUSIONS:
      Early cardiac marker gene transcript levels are significantly higher in the PBMCs
      of patients with severe stable CAD than in those of healthy controls, and show
      alterations in their expression profile according to the disease severity status.
      Our results indicate for the first time that changes in the early cardiac gene
      expression in the peripheral blood of stable CAD patients, possibly as a result
      of alterations in circulating cardiovascular progenitor cells that express these
      genes, may reflect the level of disease severity.

PMID- 24681790
TI  - Genetic variant in the CYP17 gene and risk of premature coronary artery disease.
AB  - INTRODUCTION: Sex hormones are well known to increase the risk of coronary artery
      disease (CAD). The CYP17 gene encodes the enzyme cytochrome P450c17, which
      functions at key steps during the process of human sex steroid hormone synthesis.
      A T/C polymorphism in the 5 promoter region of the CYP17 gene influences its
      expression and the resulting serum levels of androgens and estrogens. The aim of
      this casecontrol study was to investigate the role of a T/C CYP17 polymorphism in
      premature CAD and the occurrence of myocardial infarction (MI) in the Caucasian
      Greek population. METHODS: Our study group consisted of 230 CAD patients, aged
      less than 58 years, while 200 healthy individuals served as controls. The
      genotyping of the T/C CYP17 polymorphism was carried out using the PCRRFLP
      method. RESULTS: The frequencies of TT, TC, and CC genotypes were 0.38, 0.42, and
      0.20, respectively, in the patient group, and 0.35, 0.44, and 0.21, respectively,
      in the control group. Allele frequencies for the patient group were 0.58 and 0.42
      for T and C, respectively, and 0.57 and 0.43, respectively, for the control
      group. Statistical analysis revealed no significant differences between patients
      and controls in genotype frequencies (p=0.8746) or allele frequencies (p=0.6783).
      CONCLUSIONS: These findings do not support the hypothesis that the genetic
      variation T/C of the promoter of the CYP17 gene is an important contributing
      factor in the aetiology of premature CAD or occurrence of MI in the Caucasian
      Greek population.

PMID- 24681791
TI  - Surgical septal myectomy for hypertrophic cardiomyopathy in Greece: a single
      center initial experience.
AB  - INTRODUCTION: Surgical septal myectomy is thought to be the gold standard of
      treatment for obstructive hypertrophic cardiomyopathy (HCM) with obstruction
      symptoms refractory to optimal medical therapy. In Europe, during the last 2
      decades, myectomy has been set aside, while alcohol septal ablation has been
      widely promoted. In this paper, we analyze our first experience of surgical
      septal myectomy in a small cohort of patients with HCM coming from a single
      tertiary center. METHODS: Thirty-two patients (16 male, 50%) with a mean age of
      58.1 +/- 14.4 (range 12-79 years) underwent myectomy for HCM symptoms refractory
      to negative inotropic agents. The technique used for the myectomy was the one
      introduced by Andrew Morrow. Mean follow-up time after procedure was 16.8 +/-
      13.3 months with a median of 13 months (range 4-58 months). RESULTS: Post
      myectomy, there was a significant improvement in patients' NYHA class (from 3.3
      +/- 0.46 to 1.38 +/- 0.49, p<0.0005), while interventricular septum thickness was
      reduced from 2.3 +/- 0.4 cm to 1.6 +/- 0.4 cm (p<0.0005), and peak gradient at
      the site of obstruction from 94.9 +/- 29 to 16.7 +/- 7.9 mmHg (p<0.0005). During
      the follow-up period, only 1 out of 32 patients died, from non-cardiovascular
      causes, with the overall survival post-myectomy being 97.2% (95%CI: 94.5-99.9%)
      at 1-year follow up. CONCLUSIONS: Surgical septal myectomy in patients with HCM
      and drug-refractory symptoms is a safe procedure that greatly improves symptoms
      and quality of life. Further follow-up of our patients is mandatory in order to
      determine whether the good survival rate achieved at 1 year will persist.

PMID- 24681792
TI  - Epidemiology of acute coronary syndromes in the Mediterranean island of Cyprus
      (CYPACS study, Cyprus study of acute coronary syndromes).
AB  - INTRODUCTION: So far, no studies have been performed regarding the epidemiology
      and management of acute coronary syndromes (ACS) in Cyprus. The aim of the
      present study was to enroll a representative sample of patients in order to study
      the epidemiology and management of ACS in the Mediterranean island of Cyprus.
      METHODS: For a period of 12 months, all patients admitted to Nicosia General
      Hospital with an ACS were studied. The calculation of the annual incidence of ACS
      was based on the number of all ACS cases registered during one year in the
      Nicosia district. The results from the province of Nicosia can be considered as
      representative of the whole ACS profile in Cyprus. RESULTS: The annual incidence
      of ACS in the Nicosia district was 160 per 100,000 inhabitants (41 per 100,000
      women and 282 per 100,000 men). This percentage translates into 1342 ACS episodes
      annually among the Cypriot population. The ratio of men to women was 6.8:1. More
      female ACS patients than men had hypertension (67.3% vs. 46.3%, p=0.005) and were
      passive smokers (53.8% vs. 47.7%, p=0.4), while male patients with ACS included a
      significantly greater percentage of smokers compared to women (51.3% vs. 13.5%,
      p<0.001). Regarding the type of ACS, 45% of patients were diagnosed with STEMI,
      41.3% with NSTEMI and 13.7% with unstable angina. The majority of patients with
      STEMI were treated with medical reperfusion. The in-hospital mortality rate was
      3.5%. CONCLUSIONS: The annual incidence of ACS in Cyprus is below the European
      average. The management of ACS is similar to that in southern Europe. The
      majority of patients with STEMI are treated with pharmacological reperfusion. The
      small geographical area of the island provides the advantage of early reperfusion
      to the majority of patients, which results in very low in-hospital mortality.

PMID- 24681793
TI  - Long-term prognostic value of longitudinal strain of right ventricle in patients
      with moderate heart failure.
AB  - INTRODUCTION: Right ventricular (RV) systolic dysfunction is a strong prognostic
      predictor in chronic heart failure (HF). However, assessment of RV function
      remains difficult. We investigated the prognostic value of different
      echocardiographic parameters for evaluating RV function in 60 patients with
      chronic HF and a low left ventricular ejection fraction (<40%) who were on
      optimal medical treatment. METHODS: RV function was assessed using standard and
      tissue Doppler echocardiography. The following parameters were measured:
      tricuspid annular plane systolic excursion (TAPSE), right ventricular fractional
      area change (RVFAC), right myocardial performance index (MPI), tissue Doppler
      peak myocardial velocity (Sm) and longitudinal strain of the right ventricular
      wall in the basal and middle segments. RESULTS: During a mean follow-up of 32 +/-
      13 months, 6 patients died and 16 were hospitalised for HF. TAPSE, RVFAC, right
      MPI and Sm did not predict cardiovascular events. The only variable associated
      with either cardiac death or HF hospitalisation (p=0.002), or HF hospitalisation
      only (p<0.0001) was systolic longitudinal strain in the basal and middle segments
      of the RV wall. CONCLUSION: Our study demonstrates that longitudinal RV strain is
      a powerful prognostic variable for the prediction of major cardiac events in
      patients with chronic HF.

PMID- 24681794
TI  - Genetics and coronary artery disease: present and future.

PMID- 24681795
TI  - Three-dimensional echocardiography for transcatheter mitral valve paravalvular
      leak closure.

PMID- 24681796
TI  - Left atrial thrombus mimicking a myxoma in a patient with systemic lupus
      erythematosus.
AB  - Atrial masses are uncommon, and mainly consist of tumors, vegetations and
      thrombi. Despite the availability of several imaging modalities, it may still be
      difficult to distinguish between them. Atrial thrombi seen in patients with
      systemic lupus erythematosus (SLE) usually occur in the setting of anti
      phospholipid antibody syndrome, which confers a hypercoagulable state. We report
      a case of left atrial thrombus mimicking a myxoma in a patient with SLE but
      negative anti-phospholipid antibodies. 

PMID- 24681797
TI  - Echocardiographic demonstration of coronary artery to left ventricle fistulas:
      case report and review of the literature.
AB  - We describe the case of a 45-year-old female patient with coronary fistulas
      arising from both the left and right coronary artery system and emptying in the
      left ventricle. Only sporadically do coronary artery fistulas drain into the left
      ventricle. In our patient, the most likely explanation of the fistulous
      communications was a congenital cause. We review the literature on coronary
      cameral fistulas and discuss the etiology of the diagnostic findings. Small
      coronary artery fistulas are generally well-tolerated and should impose no
      significant restriction on daily routine and activities. Nevertheless, small
      fistulas may under certain conditions produce a "steal" phenomenon and shunt
      blood flow away from the myocardial capillary network, causing ischemia. 

PMID- 24681798
TI  - Transapical approach for closure of mitral periprosthetic leak.

PMID- 24681799
TI  - Stable coronary artery disease.

PMID- 24681800
TI  - Education and growth: a continuing priority.

PMID- 24681802
TI  - Independence and dependence in human causal reasoning.
AB  - Causal graphical models (CGMs) are a popular formalism used to model human causal
      reasoning and learning. The key property of CGMs is the causal Markov condition,
      which stipulates patterns of independence and dependence among causally related
      variables. Five experiments found that while adult's causal inferences exhibited
      aspects of veridical causal reasoning, they also exhibited a small but tenacious
      tendency to violate the Markov condition. They also failed to exhibit robust
      discounting in which the presence of one cause as an explanation of an effect
      makes the presence of another less likely. Instead, subjects often reasoned
      "associatively," that is, assumed that the presence of one variable implied the
      presence of other, causally related variables, even those that were (according to
      the Markov condition) conditionally independent. This tendency was unaffected by
      manipulations (e.g., response deadlines) known to influence fast and intuitive
      reasoning processes, suggesting that an associative response to a causal
      reasoning question is sometimes the product of careful and deliberate thinking.
      That about 60% of the erroneous associative inferences were made by about a
      quarter of the subjects suggests the presence of substantial individual
      differences in this tendency. There was also evidence that inferences were
      influenced by subjects' assumptions about factors that disable causal relations
      and their use of a conjunctive reasoning strategy. Theories that strive to
      provide high fidelity accounts of human causal reasoning will need to relax the
      independence constraints imposed by CGMs. 

PMID- 24681801
TI  - A high-throughput colorimetric screening assay for terpene synthase activity
      based on substrate consumption.
AB  - Terpene synthases catalyze the formation of a variety of terpene chemical
      structures. Systematic mutagenesis studies have been effective in providing
      insights into the characteristic and complex mechanisms of C-C bond formations
      and in exploring the enzymatic potential for inventing new chemical structures.
      In addition, there is growing demand to increase terpene synthase activity in
      heterologous hosts, given the maturation of metabolic engineering and host
      breeding for terpenoid synthesis. We have developed a simple screening method for
      the cellular activities of terpene synthases by scoring their substrate
      consumption based on the color loss of the cell harboring carotenoid pathways. We
      demonstrate that this method can be used to detect activities of various terpene
      synthase or prenyltransferase genes in a high-throughput manner, irrespective of
      the product type, enabling the mutation analysis and directed evolution of
      terpene synthases. We also report the possibility for substrate-specific
      screening system of terpene synthases by taking advantage of the substrate-size
      specificity of C30 and C40 carotenoid pathways. 

PMID- 24681803
TI  - Reconstructing the public in old and new governance: a Korean case of nuclear
      energy policy.
AB  - Korean nuclear energy regulatory policies started to change from earlier
      exclusively technocratic policies into open dialogues after several anti-nuclear
      protests in the 1990s. However, technocratic policies still coexist with the new
      regulatory orientation towards openness, participation and institutional
      accountability. This paper analyzes Korean nuclear regulatory policies since
      approximately 2005 as a blend of old and new governance. The aim of the paper is
      not to decide whether new nuclear governance is deliberative or not by completely
      reviewing Korean nuclear policies after the 2000s. Instead, it provides an
      empirical account of how seemingly more participatory processes in decision
      making entail new problems while they work with and reproduce social assumptions
      of different groups of the public. 

PMID- 24681804
TI  - Representations of energy policy and technology in British and Finnish newspaper
      media: a comparative perspective.
AB  - This article analyses media representations of the strengthening technological
      energy policy orientation in the UK and Finland. Drawing from over 1200 newspaper
      articles from 1991 to 2006, it scrutinises how energy policy in general and
      energy technologies in particular have been discussed by the media in these two
      countries, and how the media representations have changed over time. The results
      point to the importance of national political, economic and cultural features in
      shaping media discussions. At the same time, international political events and
      ideas of technology-driven economic growth have transformed media perceptions of
      energy technologies. While the British media have been rather critical towards
      national policies throughout the period of analysis, the Finnish newspaper
      Helsingin Sanomat has supported successive national governments. In both
      countries, energy technologies have increasingly become linked to global societal
      and political questions. 

PMID- 24681807
TI  - Skin tears: best practices for care and prevention.

PMID- 24681806
TI  - Performance of QuantiFERON-TB Gold In-Tube test and Tuberculin Skin Test for
      diagnosis of latent tuberculosis infection in BCG vaccinated health care workers.
AB  - BACKGROUND: Tuberculin skin test (TST) has been used for years as an aid in
      diagnosing latent tuberculosis infection (LTBI) but it suffers from a number of
      well-documented performance and logistic problems. Quantiferon-TB Gold In Tube
      test (QFT-GIT) has been reported to have better sensitivity and specifity than
      TST. In this study, it was aimed to compare the performance of a commercial IFN
      gamma release assay (QFT-GIT) with TST in the diagnosis of HCWs at risk for
      latent TB infection in BCG vaccinated population. MATERIAL AND METHODS: Hundred
      healthy volunteer health care workers were enrolled. All were subjected to TST
      and QFT-GIT. Results were compared among Health Care Workers (HCWs) groups in
      terms of profession, workplace, working duration. RESULTS: TST is affected by
      previous BCG vaccinations and number of cases with QFT-GIT positivity is
      increased in accordance with the TST induration diameter range. QFT-GIT result
      was negative in 17 of 32 TST positive (>= 15 mm) cases and positive in 4 of 61
      cases whose TST diameters are between 6-14 mm, that is attritutable to previous
      BCG vaccination(s). It was negative in all cases with TST diameters between 0-5
      mm. HCWs with positive QFT-GIT results were significantly older than the ones
      with negative results. Furthermore duration of work was significantly longer in
      QFT-GIT positive than in negative HCWs. CONCLUSIONS: There was a moderate
      concordance between QFT-GIT and TST, when TST result was defined as positive with
      a >= 15 mm diameter of induration. We suggest that QFT-GIT can be used as an
      alternative to TST for detection of LTBI, especially in groups with high risk of
      LTBI and in population with routine BCG vaccination program.

PMID- 24681809
TI  - Layered germanium tin antimony tellurides: element distribution, nanostructures
      and thermoelectric properties.
AB  - In the system Ge-Sn-Sb-Te, there is a complete solid solution series between
      GeSb2Te4 and SnSb2Te4. As Sn2Sb2Te5 does not exist, Sn can only partially replace
      Ge in Ge2Sb2Te5; samples with 75% or more Sn are not homogeneous. The joint
      refinement of high-resolution synchrotron data measured at the K-absorption edges
      of Sn, Sb and Te combined with data measured at off-edge wavelengths
      unambiguously yields the element distribution in 21R-Ge(0.6)Sn(0.4)Sb2Te4 and 9P
      Ge(1.3)Sn(0.7)Sb2Te5. In both cases, Sb predominantly concentrates on the
      position near the van der Waals gaps between distorted rocksalt-type slabs
      whereas Ge prefers the position in the middle of the slabs. No significant
      antisite disorder is present. Comparable trends can be found in related
      compounds; they are due to the single-side coordination of the Te atoms at the
      van der Waals gap, which can be compensated more effectively by Sb(3+) due to its
      higher charge in comparison to Ge(2+). The structure model of 21R
      Ge(0.6)Sn(0.4)Sb2Te4 was confirmed by high-resolution electron microscopy and
      electron diffraction. In contrast, electron diffraction patterns of 9P
      Ge(1.3)Sn(0.7)Sb2Te5 reveal a significant extent of stacking disorder as
      evidenced by diffuse streaks along the stacking direction. The Seebeck
      coefficient is unaffected by the Sn substitution but the thermal conductivity
      drops by a factor of 2 which results in a thermoelectric figure of merit ZT =
      ~0.25 at 450  degrees C for both Ge(0.6)Sn(0.4)Sb2Te4 and Ge(1.3)Sn(0.7)Sb2Te5,
      which is higher than ~0.20 for unsubstituted stable layered Ge-Sb-Te compounds.

PMID- 24681808
TI  - SLC25A1, or CIC, is a novel transcriptional target of mutant p53 and a negative
      tumor prognostic marker.
AB  - Mutations of the p53 gene hallmark many human cancers. Several p53 mutant
      proteins acquire the capability to promote cancer progression and metastasis, a
      phenomenon defined as Gain of Oncogenic Function (GOF). The downstream targets by
      which GOF p53 mutants perturb cellular programs relevant to oncogenesis are only
      partially known. We have previously demonstrated that SLC25A1 (CIC) promotes
      tumorigenesis, while its inhibition blunts tumor growth. We now report that CIC
      is a direct transcriptional target of several p53 mutants. We identify a novel
      interaction between mutant p53 (mutp53) and the transcription factor FOXO-1 which
      is responsible for regulation of CIC expression levels. Tumor cells harboring
      mutp53 display higher CIC levels relative to p53 null or wild-type tumors, and
      inhibition of CIC activity blunts mutp53-driven tumor growth, partially
      overcoming GOF activity. CIC inhibition also enhances the chemotherapeutic
      potential of platinum-based agents. Finally, we found that elevated CIC levels
      predict poor survival outcome in tumors hallmarked by high frequency of p53
      mutations. Our results identify CIC as a novel target of mutp53 and imply that
      the employment of CIC inhibitors may improve survival rates and reduce chemo
      resistance in tumors harboring these types of mutations, which are among the most
      intractable forms of cancers. 

PMID- 24681810
TI  - Extended-release quetiapine fumarate (quetiapine XR) versus risperidone in the
      treatment of depressive symptoms in patients with schizoaffective disorder or
      schizophrenia: a randomized, open-label, parallel-group, flexible-dose study.
AB  - Depressive symptoms are associated with poor outcomes, increased risk of relapse,
      and high suicide rates in patients with schizophrenia and schizoaffective
      disorder. This randomized, open-label, parallel-group, flexible-dose study
      (NCT00640562) assessed the efficacy of quetiapine extended release (XR) versus
      risperidone on depressive symptoms in this patient population. Noninferiority of
      quetiapine XR versus risperidone from baseline to week 12 was assessed by least
      squares mean (LSM) reduction in the Calgary Depression Scale for Schizophrenia
      (CDSS). Noninferiority was indicated if the difference in CDSS reductions between
      quetiapine XR and risperidone had a 95% confidence interval (CI) lower limit of
      more than -2.7. Overall, 216 patients received quetiapine XR (n = 109; 400-800
      mg/day) or risperidone (n = 107; 4-6 mg/day). In the per-protocol population, LSM
      CDSS reductions for quetiapine XR and risperidone were 8.4 and 6.2 points,
      respectively (95% CI 0.8-3.7). As the lower limit of the 95% CI was more than 
      2.7 and the LSM reduction for quetiapine XR was 2.2 points higher than that for
      risperidone, noninferiority of quetiapine XR versus risperidone was demonstrated.
      Adverse events for quetiapine XR and risperidone were comparable. In this study,
      quetiapine XR was noninferior to risperidone at reducing depressive symptoms in
      patients with schizophrenia or schizoaffective disorder.

PMID- 24681811
TI  - Effectiveness of long-acting injectable antipsychotics in delusional disorders
      with nonprominent hallucinations and without hallucinations.
AB  - The presence of nonprominent hallucinations in delusional disorder (DD) has been
      accepted by the current Diagnostic and Statistical Manual of Mental Disorders,
      5th ed. A recent meta-analysis revealed that patients with schizophrenia treated
      with long-acting atypical antipsychotics showed a significant improvement in
      psychotic symptoms. However, little research has been conducted on DD. Our goal
      was to investigate demographic and clinical differences between two subgroups of
      DD patients, those with nonprominent hallucinations and those without
      hallucinations, and to determine treatment effectiveness of long-acting
      antipsychotics in these patients. We conducted a longitudinal observational study
      with a 6-month follow-up period in a clinical group of 45 DD outpatients.
      Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance
      Scale, and Hamilton Rating Scale for Depression-17 (HRSD-17) were used for
      assessment. Age at onset of DD, scores in baseline assessment scales, and drug
      compliance were included in the analysis as potential confounders. When
      uncorrected for influencing factors, patients treated with long-acting
      antipsychotics showed lower scores in PANSS positive and negative subscales.
      There were no statistically significant clinical subgroup*treatment group
      interactions for any of the scores in assessment scales at 6 months. After
      adjustment, patients treated with long-acting antipsychotics showed lower scores
      in the PANSS negative subscale and a tendency toward improvement in scores in the
      PANSS positive subscale. Our study suggests that risperidone long-acting
      injection and paliperidone palmitate long-acting injection may be useful in the
      treatment of DD patients, specifically those with nonprominent hallucinations. 

PMID- 24681812
TI  - High catalytic activity and stability of nickel sulfide and cobalt sulfide
      hierarchical nanospheres on the counter electrodes for dye-sensitized solar
      cells.
AB  - In situ grown nickel sulfide and cobalt sulfide hierarchical nanospheres on F
      doped SnO2 (FTO) substrates exhibited comparable catalytic activities to
      sputtering Pt on the counter electrodes for dye-sensitized solar cells (DSSCs).
      The fresh cells with the nickel sulfide and cobalt sulfide on the counter
      electrodes could reach power conversion efficiencies of 6.81% and 6.59%
      respectively, approaching an efficiency of 6.85% based on the sputtering Pt
      counter electrode. Both nickel sulfide and cobalt sulfide counter electrodes
      could maintain the cell's relatively high performance in the long-term stability
      test in 504 hours. 

PMID- 24681813
TI  - Preventing dengue through mobile phones: evidence from a field experiment in
      Peru.
AB  - Dengue is the most rapidly spreading mosquito-borne viral disease in the world
      (WHO, 2009). During the last two decades, the dramatic rise in the number of
      dengue infections has been particularly evident in Latin American and the
      Caribbean countries. This paper examines the experimental evidence of the
      effectiveness of mobile phone technology in improving households' health
      preventive behavior in dengue-endemic areas. The main results suggest that
      repeated exposure to health information encourages households' uptake of
      preventive measures against dengue. As a result, the Breteau Index in treatment
      households, an objective measure of dengue risk transmission, is 0.10 standard
      deviations below the mean of the control group, which shows a reduction in the
      number of containers per household that test positive for dengue larvae. The
      estimates also show marginally significant effects of the intervention on self
      reported dengue symptoms. Moreover, we use a multiple treatment framework that
      randomly assigns households to one of the four treatment groups in order to
      analyze the impacts of framing on health behavior. Different variants emphasized
      information on monetary and non-monetary benefits and costs. The main results
      show no statistical differences among treatment groups. 

PMID- 24681815
TI  - Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and
      cardiovascular events among patients undergoing angiography or cardiac
      revascularization: a meta-analysis of observational studies.
AB  - OBJECTIVE: The aim of this study was to investigate whether neutrophil to
      lymphocyte ratio (NLR) was an independent predictor for all-cause mortality or
      cardiovascular events in patients undergoing angiography or cardiac
      revascularization with observational studies by meta-analysis. METHODS: Pubmed
      and Embase were searched without language restrictions for cohort studies
      published prior to November 2013. Citations were independently screened by 2
      authors, and those meeting the inclusion criteria defined a priori were retained.
      Data on authors, year of publication, location, target participant, comparison of
      NLR, outcome assessment, number of event and sample size, duration and
      statistical adjustments were abstracted. RESULTS: Eight studies were identified
      that reported on all-cause mortality and five studies were identified that
      reported on cardiovascular events. The pooled relative risk (RR) of all-cause
      mortality was 2.33 (95% CI 1.88-2.88) and the RR of cardiovascular events was
      1.89 (95% CI 1.42, 2.52) comparing the highest with the lowest category of NLR.
      CONCLUSIONS: The meta-analysis indicates that NLR is a predictor of all-cause
      mortality and cardiovascular events. Further well-designed trials are warranted
      to confirm this association.

PMID- 24681814
TI  - Glucagon-like Peptide-1 receptor signaling in the lateral parabrachial nucleus
      contributes to the control of food intake and motivation to feed.
AB  - Central glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake
      and the motivation to work for food, but the neurons and circuits mediating these
      effects are not fully understood. Although lateral parabrachial nucleus (lPBN)
      neurons are implicated in the control of food intake and reward, the specific
      role of GLP-1R-expressing lPBN neurons is unexplored. Here, neuroanatomical
      tracing, immunohistochemical, and behavioral/pharmacological techniques are used
      to test the hypothesis that lPBN neurons contribute to the anorexic effect of
      central GLP-1R activation. Results indicate that GLP-1-producing neurons in the
      nucleus tractus solitarius project monosynaptically to the lPBN, providing a
      potential endogenous mechanism by which lPBN GLP-1R signaling may exert effects
      on food intake control. Pharmacological activation of GLP-1R in the lPBN reduced
      food intake, and conversely, antagonism of GLP-1R in the lPBN increased food
      intake. In addition, lPBN GLP-1R activation reduced the motivation to work for
      food under a progressive ratio schedule of reinforcement. Taken together, these
      data establish the lPBN as a novel site of action for GLP-1R-mediated control of
      food intake and reward. 

PMID- 24681817
TI  - Going up in ashes? Smoking-attributable morbidity, hospital admissions and
      expenditure in Greece.
AB  - Our aim was to calculate the morbidity, hospitalizations and subsequent hospital
      costs for the treatment of the smoking-attributable fraction of diseases in
      Greece using a prevalence-based annual cost approach. In 2011, smoking accounted
      for 199,028 hospital admissions (8.9% of the national total), with attributable
      hospital treatment costs calculated at more than ?554 million, which represents
      10.7% of the national hospital budget. These results pose a compelling reason for
      the European Union to champion tobacco control as a means of reducing the
      financial and social burden of disease in Greece and other countries currently
      facing a financial maelstrom. 

PMID- 24681816
TI  - Association of the novel single-nucleotide polymorphism which increases oxidized
      low-density lipoprotein levels with cerebrovascular disease events.
AB  - BACKGROUND AND PURPOSE: Patients with genetic background for high circulating
      oxidized low-density lipoprotein (oxLDL) levels might be at an increased risk of
      cerebrovascular disease (CVD). METHODS: The association of oxLDL-variant rs676210
      with CVD events was studied in patients undergoing coronary angiography (study A;
      N = 2913 [271 cases]). We sought to replicate the results in a large genome-wide
      association study meta-analysis of ischaemic stroke (study B; N = 3548 cases,
      5972 controls). RESULTS: In study A, the prevalence of hypertension, diabetes and
      >50% carotid stenosis as well as the levels of LDL cholesterol differed
      significantly between cases and controls. In a logistic regression model adjusted
      for the significant covariates, rs676210 associated with CVD events (p = 0.030;
      odds ratio = 1.29 [95% confidence interval 1.03-1.63] for risk allele G). In
      study B, rs676210 did not associate with the history of ischaemic stroke.
      CONCLUSIONS: The oxLDL levels increasing variant rs676210 associates with CVD
      events in patients undergoing coronary angiography.

PMID- 24681818
TI  - Cultures of evidence across policy sectors: systematic review of qualitative
      evidence.
AB  - BACKGROUND: It is important to understand the decision-making process, and the
      role of research evidence within it, across sectors other than health, as
      interventions delivered within these sectors may have substantial impacts on
      public health and health inequalities. METHODS: Systematic review of qualitative
      evidence. Twenty-eight databases covering a range of sectors were searched.
      Studies were eligible if they included local decision-makers in a policy field
      relevant to the social determinants of health (including housing, transport,
      urban planning and regeneration, crime, licensing or trading standards), were
      conducted in a high-income country, and reported primary qualitative data on
      perceptions of research evidence. Study quality was assessed and a thematic
      synthesis undertaken. RESULTS: Sixteen studies were included, most using
      interview designs, and most focusing on planning or transport policy. Several
      factors are seen to influence decision-makers' views of evidence, including
      practical factors such as resources or organizational support; the credibility of
      the evidence; its relevance or applicability to practice; considerations of
      political support or feasibility; and legislative constraints. There are limited
      data on how evidence is used: it is sometimes used to not only support decision
      making, but also to lend legitimacy to decisions that have already been made.
      CONCLUSION: Although cultures of evidence in non-health sectors are similar to
      those in health in some ways, there are some key differences, particularly as
      regards the political context of decision-making. Intersectoral public health
      research could benefit from taking into account non-health decision makers' needs
      and preferences, particularly around relevance and political feasibility.

PMID- 24681819
TI  - Non-random DNA fragmentation in next-generation sequencing.
AB  - Next Generation Sequencing (NGS) technology is based on cutting DNA into small
      fragments, and their massive parallel sequencing. The multiple overlapping
      segments termed "reads" are assembled into a contiguous sequence. To reduce
      sequencing errors, every genome region should be sequenced several dozen times.
      This sequencing approach is based on the assumption that genomic DNA breaks are
      random and sequence-independent. However, previously we showed that for the
      sonicated restriction DNA fragments the rates of double-stranded breaks depend on
      the nucleotide sequence. In this work we analyzed genomic reads from NGS data and
      discovered that fragmentation methods based on the action of the hydrodynamic
      forces on DNA, produce similar bias. Consideration of this non-random DNA
      fragmentation may allow one to unravel what factors and to what extent influence
      the non-uniform coverage of various genomic regions. 

PMID- 24681820
TI  - Genetic variations in microRNAs and the risk and survival of renal cell cancer.
AB  - MicroRNAs (miRNAs) are a class of short non-coding, single-stranded RNAs, which
      perform posttranscriptional regulatory functions as tumor suppressors or
      oncogenes. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) genes are
      currently being identified for contributing to cancer risk, prognosis and
      survival. We investigated whether genetic variations of miRNAs were associated
      with the risk and prognosis of renal cell carcinoma (RCC). We genotyped four
      common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2
      rs11614913 and miR-499 rs3746444) to assess their associations with RCC risk in a
      two-stage case-control study (355 cases and 362 controls in discovery set,
      meanwhile 647 cases and 660 controls in validation set), as well as RCC survival
      in 311 patients. We found that the miR-196a2 SNP rs11614913 was associated with
      RCC susceptibility in recessive model [CC versus TT/TC, adjusted odds ratio =
      0.65, 95% confidence interval (CI) = 0.52-0.83] and with survival of RCC in
      dominant model (TC/CC versus TT, adjusted hazard ratio = 0.40, 95% CI = 0.18
      0.89). Meanwhile, the rs11614913 CC genotype was associated with the
      significantly decreased expression of miR-196a-5p in 26 renal cancer tissues (P =
      0.018). Moreover, luciferase reporter assays revealed the potential effect of
      rs11614913 SNP on the binding of miR-196a-3p to its targets. These results
      suggested that the miR-196a2 rs11614913 may contribute to the genetic
      susceptibility and prognosis for RCC, which may act as a biomarker for RCC
      occurrence and prognosis.

PMID- 24681821
TI  - Subgrouping of low back pain patients for targeting treatments: evidence from
      genetic, psychological, and activity-related behavioral approaches.
AB  - INTRODUCTION: Many patients with low back pain (LBP) are treated in a similar
      manner as if they were a homogenous group. However, scientific evidence is
      available that pain is a complex perceptual experience influenced by a wide range
      of genetic, psychological, and activity-related factors. The leading question for
      clinical practice should be what works for whom. OBJECTIVES: The main aim of the
      present review is to discuss the current state of evidence of subgrouping based
      on genetic, psychosocial, and activity-related factors in order to understand
      their contribution to individual differences. RESULTS: Based on these
      perspectives, it is important to identify patients based on their specific
      characteristics. For genetics, very promising results are available from other
      chronic musculoskeletal pain conditions. However, more research is warranted in
      LBP. With regard to subgroups based on psychosocial factors, the results underpin
      the importance of matching patients' characteristics to treatment. Combining this
      psychosocial profile with the activity-related behavioral style may be of added
      value in tailoring the patient's treatment to his/her specific needs.
      CONCLUSIONS: For future research and treatment it might be challenging to develop
      theoretical frameworks combining different subgrouping classifications. On the
      basis of this framework, tailoring treatments more specifically to the patient
      needs may result in improvements in treatment programs for patients with LBP.

PMID- 24681822
TI  - gdf6a is required for cone photoreceptor subtype differentiation and for the
      actions of tbx2b in determining rod versus cone photoreceptor fate.
AB  - Functional vision restoration is within reach via stem cell therapy, but one of
      the largest obstacles is the derivation of colour-sensitive cone photoreceptors
      that are required for high-acuity daytime vision. To enhance progress made using
      nocturnal murine models, we instead utilize cone-rich zebrafish and herein
      investigate relationships between gdf6a and tbx2b in cone photoreceptor
      development. Growth/differentiation factor 6a (gdf6a), a bone morphogenetic
      protein family ligand, is an emerging factor in photoreceptor degenerative
      diseases. The T-box transcription factor tbx2b is required to specify UV cone
      photoreceptor fate instead of rod photoreceptor fate. Interactions between these
      factors in cone development would be unanticipated, considering the discrete
      phenotypes in their respective mutants. However, gdf6a positively modulates the
      abundance of tbx2b transcript during early eye morphogenesis, and we extended
      this conclusion to later stages of retinal development comprising the times when
      photoreceptors differentiate. Despite this, gdf6a-/- larvae possess a normal
      relative number of UV cones and instead present with a low abundance of blue cone
      photoreceptors, approximately half that of siblings (p<0.001), supporting a
      differential role for gdf6a amongst the spectral subtypes of cone photoreceptors.
      Further, gdf6a-/- larvae from breeding of compound heterozygous gdf6a+/-;tbx2b+/-
      mutants exhibit the recessive lots-of-rods phenotype (which also shows a paucity
      of UV cones) at significantly elevated rates (44% or 48% for each of two tbx2b
      alleles, chi2 p<=0.007 for each compared to expected Mendelian 25%). Thus the
      gdf6a-/- background sensitizes fish such that the recessive lots-of-rods
      phenotype can appear in heterozygous tbx2b+/- fish. Overall, this work
      establishes a novel link between tbx2b and gdf6a in determining photoreceptor
      fates, defining the nexus of an intricate pathway influencing the abundance of
      cone spectral subtypes and specifying rod vs. cone photoreceptors. Understanding
      this interaction is a necessary step in the refinement of stem cell-based
      restoration of daytime vision in humans. 

PMID- 24681823
TI  - Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma
      by ultra high performance liquid chromatography tandem mass spectrometry and its
      application to a bioequivalence study.
AB  - An ultra high performance liquid chromatography tandem mass spectrometry (U-HPLC
      MS/MS) method was developed and validated to determine irbesartan (IRB) and
      hydrochlorothiazide (HCTZ) in human plasma simultaneously. Plasma samples were
      prepared using protein precipitation with acetonitrile, the two analytes and the
      internal standard losartan were separated on an Acquity U-HPLC BEH C18 column and
      mass spectrometric analysis was performed using a QTrap5500 mass spectrometer
      coupled with an electro-spray ionization (ESI) source in the negative ion mode.
      The MRM transitions of m/z 427.2->206.9 and m/z 296.1->204.9 were used to
      quantify for IRB and HCTZ, respectively. The linearity of this method was found
      to be within the concentration range of 5-3000ng/mL for IRB, and 0.5-300ng/mL for
      HCTZ in human plasma, respectively. The lower limit of quantification (LLOQ) was
      5ng/mL and 0.5ng/mL for IRB and HCTZ in human plasma, respectively. The relative
      standard deviations (RSD) of intra and inter precision were less than 12% for
      both IRB and HCTZ. The analysis time of per sample was 2.5min. The developed and
      validated method was successfully applied to a bioequivalence study of IRB
      (300mg) with HCTZ (12.5mg) tablet in Chinese healthy volunteers (N=20). 

PMID- 24681824
TI  - The role of high mobility group box 1 (HMGB1) in colorectal cancer.
AB  - BACKGROUND: HMGB1, the most important member of the high mobility group box
      protein family, is a nuclear protein with different functions in the cell; it has
      a role in cancer progression, angiogenesis, invasion, and metastasis development.
      We studied the expression of HMGB1 and whether it is a prognostic factor in
      colorectal carcinoma. MATERIAL AND METHODS: The study included 110 cases that
      were histopathologically diagnosed with colorectal carcinoma from the tissue
      samples acquired by surgical resection and biopsy in Antalya Education and
      Research Hospital between 2008 and 2012. HMGB1 expression was examined via
      immunohistochemical method. RESULTS: HMGB1 expression was evaluated as negative
      in 32 (44.4%) of the patients and as positive in 40 (55.6%) patients. There was
      no relation between the HMGB1 expression and sex, age, tumor invasion depth, and
      histological type. However, a significant relation was detected between the HMGB1
      expression and lymph node status, metastasis status, and stage (p:<0.001,
      p:<0.001, p:<0.001, respectively). Similar results were obtained for the
      relations between the HMGB1 and histological grade, perineural invasion,
      lymphovascular invasion, and lymphocytic response (p<0.001, p<0.001, p<0.001, and
      p<0.001, respectively). CONCLUSIONS: The results of our study demonstrate that
      HMGB1 overexpression has a significant role in tumor progression (especially
      migration of tumor cells) and tumor ability to metastasize in colorectal cancers;
      thus, it corroborates the idea that it might be an important prognostic factor.

PMID- 24681825
TI  - The NLR-related protein NWD1 is associated with prostate cancer and modulates
      androgen receptor signaling.
AB  - Prostate cancer (PCa) is among the leading causes of cancer-related death in men.
      Androgen receptor (AR) signaling plays a seminal role in prostate development and
      homeostasis, and dysregulation of this pathway is intimately linked to prostate
      cancer pathogenesis and progression. Here, we identify the cytosolic NLR-related
      protein NWD1 as a novel modulator of AR signaling. We determined that expression
      of NWD1 becomes elevated during prostate cancer progression, based on analysis of
      primary tumor specimens. Experiments with cultured cells showed that NWD1
      expression is up-regulated by the sex-determining region Y (SRY) family proteins.
      Gene silencing procedures, in conjunction with transcriptional profiling, showed
      that NWD1 is required for expression of PDEF (prostate-derived Ets factor), which
      is known to bind and co-regulate AR. Of note, NWD1 modulates AR protein levels.
      Depleting NWD1 in PCa cell lines reduces AR levels and suppresses activity of
      androgen-driven reporter genes. NWD1 knockdown potently suppressed growth of
      androgen-dependent LNCaP prostate cancer cells, thus showing its functional
      importance in an AR-dependent tumor cell model. Proteomic analysis suggested that
      NWD1 associates with various molecular chaperones commonly related to AR
      complexes. Altogether, these data suggest a role for tumor-associated over
      expression of NWD1 in dysregulation of AR signaling in PCa. 

PMID- 24681826
TI  - Virtual reality therapy for adults post-stroke: a systematic review and meta
      analysis exploring virtual environments and commercial games in therapy.
AB  - BACKGROUND: The objective of this analysis was to systematically review the
      evidence for virtual reality (VR) therapy in an adult post-stroke population in
      both custom built virtual environments (VE) and commercially available gaming
      systems (CG). METHODS: MEDLINE, CINAHL, EMBASE, ERIC, PSYCInfo, DARE, PEDro,
      Cochrane Central Register of Controlled Trials, and Cochrane Database of
      Systematic Reviews were systematically searched from the earliest available date
      until April 4, 2013. Controlled trials that compared VR to conventional therapy
      were included. Population criteria included adults (>18) post-stroke, excluding
      children, cerebral palsy, and other neurological disorders. Included studies were
      reported in English. Quality of studies was assessed with the Physiotherapy
      Evidence Database Scale (PEDro). RESULTS: Twenty-six studies met the inclusion
      criteria. For body function outcomes, there was a significant benefit of VR
      therapy compared to conventional therapy controls, G = 0.48, 95% CI = [0.27,
      0.70], and no significant difference between VE and CG interventions (P = 0.38).
      For activity outcomes, there was a significant benefit of VR therapy, G = 0.58,
      95% CI = [0.32, 0.85], and no significant difference between VE and CG
      interventions (P = 0.66). For participation outcomes, the overall effect size was
      G = 0.56, 95% CI = [0.02, 1.10]. All participation outcomes came from VE studies.
      DISCUSSION: VR rehabilitation moderately improves outcomes compared to
      conventional therapy in adults post-stroke. Current CG interventions have been
      too few and too small to assess potential benefits of CG. Future research in this
      area should aim to clearly define conventional therapy, report on participation
      measures, consider motivational components of therapy, and investigate
      commercially available systems in larger RCTs. TRIAL REGISTRATION: Prospero
      CRD42013004338.

PMID- 24681828
TI  - Estradiol stimulates mitochondrial biogenesis and adiponectin expression in
      skeletal muscle.
AB  - Sexual dimorphism has been found in mitochondrial features of skeletal muscle,
      with female rats showing greater mitochondrial mass and function compared with
      males. Adiponectin is an insulin-sensitizing adipokine whose expression has been
      related to mitochondrial function and that is also expressed in skeletal muscle,
      where it exerts local metabolic effects. The aim of this research was to
      elucidate the role of sex hormones in modulation of mitochondrial function, as
      well as its relationship with adiponectin production in rat skeletal muscle. An
      in vivo study with ovariectomized Wistar rats receiving or not receiving 17beta
      estradiol (E2) (10 MUg/kg per 48 h for 4 weeks) was carried out, in parallel with
      an assay of cultured myotubes (L6E9) treated with E2 (10 nM), progesterone (Pg; 1
      MUM), or testosterone (1 MUM). E2 upregulated the markers of mitochondrial
      biogenesis and dynamics, and also of mitochondrial function in skeletal muscle
      and L6E9. Although in vivo E2 supplementation only partially restored the
      decreased adiponectin expression levels induced by ovariectomy, these were
      enhanced by E2 and Pg treatment in cultured myotubes, whereas testosterone showed
      no effects. Adiponectin receptor 1 expression was increased by E2 treatment, both
      in vivo and in vitro, but testosterone decreased it. In conclusion, our results
      are in agreement with the sexual dimorphism previously reported in skeletal
      muscle mitochondrial function and indicate E2 to be its main effector, as it
      enhances mitochondrial function and diminishes oxidative stress. Moreover, our
      data support the idea of the existence of a link between mitochondrial function
      and adiponectin expression in skeletal muscle, which could be modulated by sex
      hormones. 

PMID- 24681829
TI  - Advanced glycation end products are associated with arterial stiffness in type 1
      diabetes.
AB  - The aim of this study was to investigate the relationship between advanced
      glycation end products (AGEs) and arterial stiffness (AS) in subjects with type 1
      diabetes without clinical cardiovascular events. A set of 68 patients with type 1
      diabetes and 68 age- and sex-matched healthy subjects were evaluated. AGEs were
      assessed using serum concentrations of N-carboxy-methyl-lysine (CML) and using
      skin autofluorescence. AS was assessed by aortic pulse wave velocity (aPWV),
      using applanation tonometry. Patients with type 1 diabetes had higher serum
      concentrations of CML (1.18 vs 0.96 MUg/ml; P=0.008) and higher levels of skin
      autofluorescence (2.10 vs 1.70; P<0.001) compared with controls. These
      differences remained significant after adjustment for classical cardiovascular
      risk factors. Skin autofluorescence was positively associated with aPWV in type 1
      diabetes (r=0.370; P=0.003). No association was found between CML and aPWV. Skin
      autofluorescence was independently and significantly associated with aPWV in
      subjects with type 1 diabetes (beta=0.380; P<0.001) after adjustment for
      classical cardiovascular risk factors. Additional adjustments for HbA1c, disease
      duration, and low-grade inflammation did not change these results. In conclusion,
      skin accumulation of autofluorescent AGEs is associated with AS in subjects with
      type 1 diabetes and no previous cardiovascular events. These findings indicate
      that determination of tissue AGE accumulation may be a useful marker for AS in
      type 1 diabetes. 

PMID- 24681830
TI  - Vection in patients with glaucoma.
AB  - PURPOSE: Large moving scenes can induce a sensation of self-motion in stationary
      observers. This illusion is called "vection." Glaucoma progressively affects the
      functioning of peripheral vision, which plays an important role in inducing
      vection. It is still not known whether vection can be induced in these patients
      and, if it can, whether the interaction between visual and vestibular inputs is
      solved appropriately. The aim of this study was to investigate vection responses
      in patients with mild to moderate open-angle glaucoma. METHODS: Fifteen patients
      with mild to moderate glaucoma and 15 age-matched controls were exposed to a
      random-dot pattern at a short viewing distance and in a dark room. The pattern
      was projected on a large screen and rotated clockwise with an angular speed of 45
      degrees per second to induce a sensation of self-rotation. Vection latency,
      vection duration, and objective and subjective measures of tilt were obtained in
      three viewing conditions (binocular, and monocular with each eye). Each condition
      lasted 2 minutes. RESULTS: Patients with glaucoma had longer vection latencies (p
      = 0.005) than, but the same vection duration as, age-matched controls. Viewing
      condition did not affect vection responses for either group. The control group
      estimated the tilt angle as being significantly larger than the actual maximum
      tilt angle measured with the tilt sensor (p = 0.038). There was no relationship
      between vection measures and visual field sensitivity for the glaucoma group.
      CONCLUSIONS: These findings suggest that, despite an altered visual input that
      delays vection, the neural responses involved in canceling the illusion of self
      motion remain intact in patients with mild peripheral visual field loss.

PMID- 24681827
TI  - Protein phosphatases in pancreatic islets.
AB  - The prevalence of diabetes is increasing rapidly worldwide. A cardinal feature of
      most forms of diabetes is the lack of insulin-producing capability, due to the
      loss of insulin-producing beta-cells, impaired glucose-sensitive insulin
      secretion from the beta-cell, or a combination thereof, the reasons for which
      largely remain elusive. Reversible phosphorylation is an important and versatile
      mechanism for regulating the biological activity of many intracellular proteins,
      which, in turn, controls a variety of cellular functions. For instance,
      significant changes in protein kinase activities and in protein phosphorylation
      patterns occur subsequent to the stimulation of insulin release by glucose.
      Therefore, the molecular mechanisms regulating the phosphorylation of proteins
      involved in the insulin secretory process by the beta-cell have been extensively
      investigated. However, far less is known about the role and regulation of protein
      dephosphorylation by various protein phosphatases. Herein, we review extant data
      implicating serine/threonine and tyrosine phosphatases in various aspects of
      healthy and diabetic islet biology, ranging from control of hormonal stimulus
      secretion coupling to mitogenesis and apoptosis. 

PMID- 24681831
TI  - Vergence facility with stereoscopic and nonstereoscopic targets.
AB  - PURPOSE: To compare vergence facility with nonstereo and stereo targets in
      binocular symptomatic and asymptomatic subjects. METHODS: Sixty-six students were
      divided into symptomatic and asymptomatic groups according to the Convergence
      Insufficiency Symptom Survey Questionnaire score. Vergence facility was tested at
      40 cm by flipper prism 3Delta BI/12Delta BO (BI, base-in; BO, base-out). The
      targets used were a nonstereo target (a vertical column of small letter "E" of
      ~20/30 size), a stereo-local target (fifth set of circles of the Titmus test with
      stereoacuity of 100 arcsec), and a stereo-global target (page 6 of the TNO test
      with stereoacuity of 120 arcsec). RESULTS: Repeated-measures analysis of variance
      showed differences in the mean vergence facility with different targets in all
      subjects and separately in two symptom groups (p < 0.001). In all subjects and
      separately in the symptomatic subjects, this difference was statistically
      significant among the three different targets (p < 0.05). In the asymptomatic
      subjects, this difference was not significant between the measured values with
      nonstereo and stereo-local targets (p > 0.05) but significant for the comparison
      of stereo-global targets with the other two targets. The receiver operating
      characteristic curve analysis showed the cutoff points 10.5, 10.5, and 9.75
      cycles per minute with nonstereo, stereo-local, and stereo-global targets,
      respectively. The sensitivity of the three targets used was the same (97%).
      Specificity was 0.93 or higher with all three targets, with the highest
      specificity obtained with the stereo-global target (100%). CONCLUSIONS: The
      highest vergence facility was obtained with a nonstereo target and the lowest was
      obtained with a stereo-global target. High sensitivity with all three targets
      means that there are few false-negative results with them, and the high
      specificity is indicative of low false-positive results. Hence, the vergence
      facility predictive value would be high in diagnosing binocular symptomatic
      patients using a 3Delta BI/12Delta BO prism flipper at near and a response cutoff
      of about 10 cycles per minute or less.

PMID- 24681832
TI  - Optical quality and vision with iris-coloring soft contact lenses.
AB  - PURPOSE: To study the influence of iris-coloring soft contact lenses, designed
      for changing apparent iris color, on optical quality and vision. METHODS: Eighty
      subjects were included in this study. All participants were classified as
      emmetropic, with monocular best-corrected visual acuity of 20/20 or better. For
      40 subjects, we measured the optical quality (aberrations, the Strehl ratio, and
      the objective scattering index) and visual performance before and after wearing
      the cosmetic soft contact lenses. We also measured the optical quality and visual
      performance for the other 40 subjects but with a different kind of lens (fantasy
      soft contact lenses). RESULTS: Iris-coloring soft contact lenses significantly
      increased coma-like and total higher-order aberrations and objective scattering
      index (p < 0.05). We also found a significant deterioration in the Strehl ratio.
      The contrast sensitivity function significantly decreased only after wearing the
      fantasy soft contact lenses (p = 0.047). CONCLUSIONS: Iris-coloring soft contact
      lenses deteriorate the optical quality and worsen the contrast sensitivity
      function. Iris-coloring soft contact lens wearers should be informed about the
      effects on optical quality and visual function.

PMID- 24681833
TI  - Terrien's marginal degeneration accompanied by latticed stromal opacities.
AB  - PURPOSE: We report a case of Terrien's marginal degeneration (TMD) with a
      unilaterally typical narrow band of peripheral corneal stroma thinning,
      accompanied by the presence of an unusual network of opacities diffusing
      throughout the anterior stroma layers. CASE REPORT: A 43-year-old woman presented
      with superior nasal peripheral corneal thinning and an unusual network of
      polygonal stromal opacities in the anterior corneal stroma of the right eye.
      Latticed corneal changes were unusually extensive and distributed diffusely in
      the stroma. No abnormalities were found in the corneal epithelium and in the
      basal epithelial cells. No noticeable changes were found in the left eye. Because
      of a progressively worse ocular irritation of the right eye, a diagnosis of TMD
      was made for this patient. CONCLUSIONS: This case of TMD accompanied by
      keratopathy was unusual. The branching stromal lattice pattern of the corneal
      opacities was difficult to distinguish from lattice corneal dystrophy. In this
      case, the polygonal stromal opacities were located in the anterior corneal stroma
      and therefore were distinguished from a similar manifestation in posterior
      crocodile shagreen.

PMID- 24681834
TI  - Sensitive detection of polynucleotide kinase using rolling circle amplification
      induced chemiluminescence.
AB  - We develop a new method for the sensitive detection of polynucleotide kinase
      (PNK) using rolling circle amplification-induced chemiluminescence. This method
      exhibits high sensitivity with a detection limit of 2.20 * 10(-4) U mL(-1), which
      is superior to most reported approaches. Moreover, this method can be used to
      screen both the inhibitors and the activators of PNK, and can be further applied
      for real sample analysis. 

PMID- 24681835
TI  - Revised crystal structure and luminescent properties of gadolinium oxyfluoride
      Gd4O3F6 doped with Eu3+ ions.
AB  - The structure of gadolinium oxyfluoride nanoparticles was revised. Extensive
      studies including X-ray diffraction and Rietveld refinement as well as Fourier
      transform infrared spectroscopy and Raman spectroscopy confirmed the monoclinic
      P12/c1 crystal structure of Gd4O3F6. Morphological analysis using transmission
      electron microscopy showed the nanocrystallinity of the materials prepared via
      the sol-gel Pechini's method. The luminescent properties of the prepared
      materials with different concentrations of Eu(3+) ions were characterized by
      emission spectroscopy. The phosphors obtained were investigated in the vacuum
      ultraviolet range using synchrotron radiation. The Judd-Ofelt parameters (Omega2,
      Omega4) and emission efficiencies eta were calculated and are discussed in
      detail. 

PMID- 24681836
TI  - Glucocorticoids and irreversible damage in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: The aim of this study was to analyse the relationship between
      glucocorticoids and damage accrual in SLE. METHODS: We report an observational
      cohort study including 230 patients with SLE enrolled at diagnosis with 5 years
      of follow-up. Damage was calculated using the SLICC damage index. Glucocorticoid
      related damage was defined as avascular osteonecrosis, osteoporotic fractures,
      diabetes mellitus or cataracts. Prednisone doses were calculated at the end of
      the fourth year of follow-up (prednisone-4). A categorical prednisone-4 variable
      was constructed: no prednisone, <=7.5 mg/day (low dose), >7.5 mg/day (medium-high
      dose). The relationship between methylprednisolone pulses and damage was also
      tested. RESULTS: By the fifth year, 188 patients (82%) had been treated with
      prednisone. Eighty-seven patients (37.8%) had accrued damage at 5 years. Patients
      with damage at year 5 had received a higher mean daily prednisone-4 dose (10.4 vs
      6 mg/day, P < 0.001). The mean daily prednisone-4 dose was higher in patients
      accruing glucocorticoid-attributable damage (11 vs 7 mg/day, P = 0.04). Patients
      taking medium-high doses of prednisone-4 had a higher risk of accruing damage
      than those taking no prednisone [adjusted odds ratio (OR) 5.39, 95% CI 1.59,
      18.27]. Patients taking medium-high doses of prednisone-4 were more likely to
      develop glucocorticoid-related damage than those on no prednisone (adjusted OR
      9.9, 95% CI 1.1, 84). No differences were seen between patients on low doses and
      those on no prednisone. The cumulative dose of i.v. methylprednisolone-4 was not
      associated with global or glucocorticoid-related damage. CONCLUSION: Prednisone
      causes damage in SLE. Doses <7.5 mg/day and methylprednisolone pulses are not
      associated with damage accrual.

PMID- 24681837
TI  - Alopecia induced by tumour necrosis factor-alpha antagonists: description of 52
      cases and disproportionality analysis in a nationwide pharmacovigilance database.
AB  - OBJECTIVES: The aim of this research was to describe the cases of TNF-alpha
      antagonist-related alopecia reported in the French Pharmacovigilance Database
      (FPVD) and to investigate the association between exposure to TNF-alpha
      antagonists and occurrence of alopecia. METHODS: All spontaneous reports of TNF
      alpha antagonist-related alopecia recorded in the FPVD between January 2000 and
      April 2012 were colligated and described. We conducted disproportionality
      analyses (case/non-case method) to assess the link between the occurrence of
      alopecia and exposure to TNF-alpha antagonists. Cases were all reports of
      alopecia and non-cases were all other reports recorded during the study period.
      Exposure to TNF-alpha antagonists was sought in cases and in non-cases. Reporting
      odds ratios (RORs) were calculated to assess the association. Docetaxel was used
      as positive control and acetaminophen as negative control. We performed
      sensitivity analyses excluding cases of androgenic alopecia and those occurring
      in psoriatic patients. RESULTS: Among 282 590 spontaneous reports of adverse drug
      reactions (ADRs) collated in the FPVD, 1068 cases (alopecia reports) were
      identified. Of these cases, 52 (4.9%) occurred during exposure to TNF-alpha
      antagonists (18 involved infliximab, 17 adalimumab, 15 etanercept and 2
      certolizumab). Exposure to TNF-alpha antagonists was more frequent among alopecia
      reports than among other ADR reports for all TNF-alpha antagonists pooled (ROR
      3.0, 95% CI 2.3, 4.0) as well as for each antagonist separately, with similar
      values. Sensitivity analyses yielded similar results. The RORs were 29.9 (95% CI
      25.3, 35.5) with docetaxel and 0.3 (95% CI 0.2, 0.4) with acetaminophen.
      CONCLUSION: The present study confirms a strong link between TNF-alpha antagonist
      exposure (class effect) and the occurrence of alopecia.

PMID- 24681838
TI  - Comment on: A case of certolizumab-induced interstitial lung disease in a patient
      with rheumatoid arthritis.

PMID- 24681839
TI  - Utility of fluorodeoxyglucose positron emission tomography/computed tomography
      for early diagnosis and evaluation of disease activity of relapsing
      polychondritis: a case series and literature review.
AB  - OBJECTIVE: Relapsing polychondritis (RPC) is relatively rare and early diagnosis
      is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for
      the diagnosis of RPC and evaluation of disease activity. METHODS: Five RPC
      patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were
      studied. Eight RPC cases examined by PET reported in the literature were also
      assessed. Data from a total of 13 patients were analysed. RESULTS: Typical FDG
      accumulation was noted in the tracheobronchial trees of nine patients, the costal
      cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses
      of three, auricles of three, lymph nodes of three and the aorta of one. One
      patient showed nasal chondritis on a PET scan despite the absence of nasal
      changes on physical examination. Of five patients with costochondritis, four
      remained asymptomatic. Of nine patients with airway FDG accumulation, eight
      developed respiratory symptoms and all had CT abnormalities. In the other
      patient, airway FDG accumulation was evident despite the absence of airway
      symptoms and a lack of abnormalities in the respiratory function test and CT. PET
      also revealed bronchial chondritis in asymptomatic patients. The mean maximum
      standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d.
      2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after
      treatment, FDG accumulation had diminished with symptomatic and inflammatory
      improvement. CONCLUSION: FDG-PET/CT is a potentially powerful tool for the early
      diagnosis of RPC, especially in patients without easily biopsied organ
      involvement. This modality also facilitates evaluation of disease extent and
      disease activity during treatment.

PMID- 24681840
TI  - Safety of resuming tumour necrosis factor inhibitors in patients who developed
      tuberculosis as a complication of previous TNF inhibitors.
AB  - OBJECTIVES: There is no consensus on whether restarting TNF inhibitors (TNFis)
      after treatment of an active tuberculosis (TB) infection caused by previous TNFi
      exposure is safe. In this study we sought to determine the safety of resuming
      TNFis in patients following TB treatment. METHODS: The medical records of all
      patients (n = 683) that received TNFi treatment at a single rheumatology clinic
      between June 2003 and December 2012 were retrospectively reviewed. Among them,
      data from patients who developed active TB infection were collected and patient
      outcomes were evaluated for those who resumed TNFis after TB treatment. RESULTS:
      Of 683 patients, 13 patients developed an active TB infection during TNFi
      treatment (4 on etanercept, 4 on adalimumab and 5 on infliximab). The median
      duration of TNFi treatment before TB infection was 20 months. TNFi treatment was
      reinitiated in six patients: four within 2 months after TB treatment and two
      after completion of TB treatment. Four patients reinitiated with the same TNFi,
      whereas two patients started with another TNFi. During a mean follow-up of 30.6
      months, all six patients successfully completed TB treatment with no TB infection
      relapses. CONCLUSION: Our results suggest that resuming TNFi therapy in patients
      following adequate TB treatment is safe, even before completion of TB treatment.

PMID- 24681841
TI  - Comment on: A case of certolizumab-induced interstitial lung disease in a patient
      with rheumatoid arthritis: reply.

PMID- 24681842
TI  - Fluorescence-based visualization of autophagic activity predicts mouse embryo
      viability.
AB  - Embryo quality is a critical parameter in assisted reproductive technologies.
      Although embryo quality can be evaluated morphologically, embryo morphology does
      not correlate perfectly with embryo viability. To improve this, it is important
      to understand which molecular mechanisms are involved in embryo quality control.
      Autophagy is an evolutionarily conserved catabolic process in which cytoplasmic
      materials sequestered by autophagosomes are degraded in lysosomes. We previously
      demonstrated that autophagy is highly activated after fertilization and is
      essential for further embryonic development. Here, we developed a simple
      fluorescence-based method for visualizing autophagic activity in live mouse
      embryos. Our method is based on imaging of the fluorescence intensity of GFP-LC3,
      a versatile marker for autophagy, which is microinjected into the embryos. Using
      this method, we show that embryonic autophagic activity declines with advancing
      maternal age, probably due to a decline in the activity of lysosomal hydrolases.
      We also demonstrate that embryonic autophagic activity is associated with the
      developmental viability of the embryo. Our results suggest that embryonic
      autophagic activity can be utilized as a novel indicator of embryo quality. 

PMID- 24681843
TI  - Development, production, and postmarketing surveillance of hepatitis A vaccines
      in China.
AB  - China has long experience using live attenuated and inactivated vaccines against
      hepatitis A virus (HAV) infection. We summarize this experience and provide
      recent data on adverse events after immunization (AEFIs) with hepatitis A
      vaccines in China. We reviewed the published literature (in Chinese and English)
      and the published Chinese regulatory documents on hepatitis A vaccine
      development, production, and postmarketing surveillance of AEFI. We described the
      safety, immunogenicity, and efficacy of hepatitis A vaccines and horizontal
      transmission of live HAV vaccine in China. In clinical trials, live HAV vaccine
      was associated with fever (0.4%-5% of vaccinees), rash (0%-1.1%), and elevated
      alanine aminotransferase (0.015%). Inactivated HAV vaccine was associated with
      fever (1%-8%), but no serious AEFIs were reported. Live HAV vaccine had
      seroconversion rates of 83% to 91%, while inactivated HAV vaccine had
      seroconversion rates of 95% to 100%. Community trials showed efficacy rates of
      90% to 95% for live HAV and 95% to 100% for inactivated HAV vaccine.
      Postmarketing surveillance showed that HAV vaccination resulted in an AEFI
      incidence rate of 34 per million vaccinees, which accounted for 0.7% of adverse
      events reported to the China AEFI monitoring system. There was no difference in
      AEFI rates between live and inactivated HAV vaccines. Live and inactivated HAV
      vaccines manufactured in China were immunogenic, effective, and safe. Live HAV
      vaccine had substantial horizontal transmission due to vaccine virus shedding;
      thus, further monitoring of the safety of virus shedding is warranted.

PMID- 24681844
TI  - Pediatricians' practice location choice-Evaluating the effect of Japan's 2004
      postgraduate training program on the spatial distribution of pediatricians.
AB  - OBJECTIVES: To explore determinants of change in pediatrician supply in Japan,
      and examine impacts of a 2004 reform of postgraduate medical education on
      pediatricians' practice location choice. METHODS: Data were compiled from
      secondary data sources. The dependent variable was the change in the number of
      pediatricians at the municipality ("secondary tier of medical care" [STM]) level.
      To analyze the determinants of pediatrician location choices, we considered the
      following predictors: initial ratio of pediatricians per 1000 children under five
      years of age (pediatrician density) and under-5 mortality as measures of local
      area need, as well as measures of residential quality. Ordinary least-squares
      regression models were used to estimate the associations. A coefficient equality
      test was performed to examine differences in predictors before and after 2004.
      Basic comparisons of pediatrician coverage in the top and bottom 10% of STMs were
      conducted to assess inequality in pediatrician supply. RESULTS: Increased supply
      was inversely associated with baseline pediatrician density both in the pre
      period and post-period. Estimated impact of pediatrician density declined over
      time (P = 0.026), while opposite trends were observed for measures of residential
      quality. More specifically, urban centers and the SES composite index were
      positively associated with pediatrician supply for the post-period, but no such
      associations were found for the pre-period. Inequality in pediatrician
      distribution increased substantially after the reform, with the best-served 10%
      of communities benefitting from five times the pediatrician coverage compared to
      the least-served 10%. CONCLUSIONS: Residential quality increasingly became a
      function of location preference rather than public health needs after the reform.
      New placement schemes should be developed to achieve more equity in access to
      pediatric care.

PMID- 24681845
TI  - Expert perspectives on evidence-based treatment planning for patients with
      hepatocellular carcinoma.

PMID- 24681846
TI  - Development of a T cell receptor targeting an HLA-A*0201 restricted epitope from
      the cancer-testis antigen SSX2 for adoptive immunotherapy of cancer.
AB  - The clinical success of adoptive immunotherapy of cancer relies on the selection
      of target antigens that are highly expressed in tumor cells but absent in
      essential normal tissues. A group of genes that encode the cancer/testis or
      cancer germline antigens have been proposed as ideal targets for immunotherapy
      due to their high expression in multiple cancer types and their restricted
      expression in immunoprivileged normal tissues. In the present work we report the
      isolation and characterization of human T cell receptors (TCRs) with specificity
      for synovial sarcoma X breakpoint 2 (SSX2), a cancer/testis antigen expressed in
      melanoma, prostate cancer, lymphoma, multiple myeloma and pancreatic cancer,
      among other tumors. We isolated seven HLA-A2 restricted T cell receptors from
      natural T cell clones derived from tumor-infiltrated lymph nodes of two SSX2
      seropositive melanoma patients, and selected four TCRs for cloning into
      retroviral vectors. Peripheral blood lymphocytes (PBL) transduced with three of
      four SSX2 TCRs showed SSX241-49 (KASEKIFYV) peptide specific reactivity, tumor
      cell recognition and tetramer binding. One of these, TCR-5, exhibited tetramer
      binding in both CD4 and CD8 cells and was selected for further studies. Antigen
      specific and HLA-A*0201-restricted interferon-gamma release, cell lysis and
      lymphocyte proliferation was observed following culture of TCR engineered human
      PBL with relevant tumor cell lines. Codon optimization was found to increase TCR
      5 expression in transduced T cells, and this construct has been selected for
      development of clinical grade viral vector producing cells. The tumor-specific
      pattern of expression of SSX2, along with the potent and selective activity of
      TCR-5, makes this TCR an attractive candidate for potential TCR gene therapy to
      treat multiple cancer histologies. 

PMID- 24681848
TI  - Conditions and mechanism for the appearance of interlobar fissures as 5-line
      signs in axial maximum intensity projection images.
AB  - PURPOSE: To assess the conditions and mechanism for the 5-line sign of normal
      interlobar fissures revealed on axial maximum intensity projection (MIP).
      SUBJECTS AND METHODS: Fifty subjects (32 males and 18 females aged 16 to 76
      years) whose conditions were diagnosed as normal on computed tomography (CT) of
      the chest were presented. Images for the fissures with a slice thickness of 1.25
      mm, a space thickness of 1.25 mm, and an MIP slab thickness of 6.25 mm were
      reconstructed. RESULTS: A 5-line shadow of normal interlobar fissures was shown
      on axial MIP imaging using a slab thickness of 6.25 mm. On axial MIP imaging, 93%
      of interlobar fissure parts were manifested as clear or barely clear.
      CONCLUSIONS: On axial MIP imaging using a slab thickness of 6.25 mm, normal
      interlobar fissures were displayed as 5-line signs, which, similar to the beaded
      small lung vessels shown on MIP imaging, might be a partial volume-averaging
      phenomenon.

PMID- 24681847
TI  - The immunocytokine NHS-IL12 as a potential cancer therapeutic.
AB  - Targeted delivery of IL-12 might turn this cytokine into a safer, more effective
      cancer therapeutic. Here we describe a novel immunocytokine, NHS-IL12, consisting
      of two molecules of IL-12 fused to a tumor necrosis-targeting human IgG1 (NHS76).
      The addition of the human IgG1 moiety resulted in a longer plasma half-life of
      NHS-IL12 than recombinant IL-12, and a selective targeting to murine tumors in
      vivo. Data from both in vitro assays using human PBMCs and in vivo primate
      studies showed that IFN-gamma production by immune cells is attenuated following
      treatment with the immunocytokine, suggesting an improved toxicity profile than
      seen with recombinant IL-12 alone. NHS-IL12 was superior to recombinant IL-12
      when evaluated as an anti-tumor agent in three murine tumor models. Mechanistic
      studies utilizing immune cell subset-depleting antibodies, flow cytometric
      methods, and in vitro cytotoxicity and ELISA assays all indicated that the anti
      tumor effects of NHS-IL12 were primarily CD8+ T cell-dependent and likely IL-12
      mediated. Combining NHS-IL12 treatment with a cancer vaccine, radiation, or
      chemotherapy resulted in greater anti-tumor effects than each individual therapy
      alone. These preclinical findings provide a rationale for the clinical testing of
      this immunocytokine, both as a single agent and in combination with vaccines,
      radiation and chemotherapy. 

PMID- 24681849
TI  - Value of enhancement technique in 3D-T2-STIR images of the brachial plexus.
AB  - OBJECTIVE: Imaging the brachial plexus is a challenge because of its complicated
      structure. The purpose of this study is to improve the diagnostic ability for
      brachial plexus via 3-dimensional T2-weighted short inversion time inversion
      recovery (3D-T2-STIR) technique with contrast agent administration. METHODS:
      Thirty patients with brachial plexopathies were recruited. The STIR sequences
      without and with contrast agent administration were performed on each subject.
      The grade of the diagnostic ability and the contrast ratio were assessed.
      RESULTS: After contrast agent administration, signals of the adjacent vessels
      were suppressed because of reduced T1 relaxation time similar to that of fat
      tissues. The outlines of nerves would be prominent with respect to surrounding
      tissues. Both diagnostic ability and contrast ratio were improved on 3D-T2-STIR
      with contrast agent administration. CONCLUSIONS: The maximum-intensity projection
      image of 3D-T2-STIR technique with contrast agent was superior to that without.
      It might be a better way to evaluate anatomies and pathologies of the brachial
      plexus. These advantages would improve the understanding and neurosurgical
      planning for brachial plexopathies in the future.

PMID- 24681850
TI  - Postoperative low-dose follow-up computed tomography for patients with stomach
      cancer: optimal blending ratio of adaptive statistical iterative reconstruction
      for image quality and diagnostic performance.
AB  - OBJECTIVE: To compare the diagnostic performance of adaptive statistical
      iterative reconstruction applied low-dose computed tomography (CT) (LDCT) with
      that of the standard-dose CT (SDCT) for local recurrence in patients with stomach
      cancer. METHODS: Seventy-nine consecutive patients who had undergone surgical
      resection for stomach cancer were enrolled. To monitor recurrence, SDCT (120
      kilovolt peak [kVp], 200mAs) had been performed. The LDCT (120 kVp, 100 mA s) was
      taken, and images were reconstructed with 4 levels of adaptive statistical
      iterative reconstruction (ASIR) blending (0%, 30%, 50%, and 70%). Two blinded
      radiologists recorded the diagnostic confidence scores for local recurrence in
      each data set using a 5-point scale. Endoscopic biopsy results served as the
      reference standard. Receiver operating characteristic (ROC) curve analysis was
      used to calculate the diagnostic performance. RESULTS: The diagnostic performance
      of LDCT with variable ASIR blending ratios was comparable to that of SDCT (area
      under ROC curve, 0.727-0.734, 0.687, respectively, P > 0.05). CONCLUSIONS: The
      diagnostic performance of ASIR applied LDCT is comparable to that of SDCT.

PMID- 24681851
TI  - Functional volumetric MRI in assessing treatment response to intra-arterial
      therapy of primary and secondary liver tumors.
AB  - The assessment of tumor response after intra-arterial therapy (IAT) is useful to
      determine treatment success, to guide future treatments, and to predict patient
      outcome. Changes in tumor size in the axial plane after transarterial therapies
      might be delayed with the traditional criteria, whereas cellular tumor changes
      can be detected earlier by functional metrics such as vascular enhancement and
      cellular integrity in the entire tumor volume. Magnetic resonance imaging has
      become an important tool in the evaluation of early tumor response with the
      introduction of new techniques, such as diffusion-weighted imaging and apparent
      diffusion coefficient maps, and the development of advanced software to quantify
      vascular enhancement after IATs. This review discusses the role of treatment
      response by functional volumetric imaging after IAT in patients with primary and
      secondary liver tumors. 

PMID- 24681852
TI  - Change in postsurgical cavity size within the first 30 days correlates with
      extent of surrounding edema: consequences for postoperative radiosurgery.
AB  - OBJECTIVE: Resection cavity diameter of less than 40 mm is required to be
      eligible for stereotactic radiosurgery (SRS), after gross total resection of
      brain metastasis at our institution. Our study evaluates the correlation between
      vasogenic edema and change in cavity size for 30 days. METHODS: Cavity size was
      measured on the postoperative and follow-up magnetic resonance imaging. Vasogenic
      edema was quantified as the largest axial measurement of T2 hyperintensity
      surrounding the resection cavity (postoperative magnetic resonance imaging).
      RESULTS: Thirty-nine resection cavities (37 patients) were reviewed. There was a
      statistically significant (Pearson coefficient = -0.35; P = 0.02) negative
      correlation between edema and change in cavity size. An arbitrary cutoff value of
      a 15-mm edema yielded a sensitivity of 96% and a specificity of 65% (P < 0.001)
      to predict 10% decrease in cavity size. CONCLUSIONS: In patients with cavity size
      close to the size cutoff for SRS, rescanning closer to the date of SRS should be
      considered, especially if there is significant edema surrounding the cavity.

PMID- 24681853
TI  - Validation of compliance zone at cerebral arterial bifurcation using phantom and
      computational fluid dynamics simulation.
AB  - OBJECTIVE: A zone compliant to pulsatile flow (compliance zone) showing
      evagination and flattening at the apex of the cerebral arterial bifurcation was
      documented in our previous report using electrocardiogram-gated computed
      tomographic and magnetic resonance angiography. We aimed to validate the
      existence of compliance zones and examine their relationship to local thin
      elastic walls. METHODS: We examined different bifurcating vascular models: a
      phantom with a thin elastic region at the apex and computational fluid dynamics
      models with either an elastic or rigid region at the apex of a bifurcation.
      RESULTS: In the phantom, the elastic region at the apex of the bifurcation showed
      evagination and flattening in time with the pulsatile circulating fluids. The
      size of the evaginations increased when the outlet side was tilted down below the
      level of the flow-generating pump. Pulsatile evagination could be simulated in
      the computational fluid dynamics model with an elastic region at the bifurcation
      apex, and the pressure gradient was highest in the evaginating apex in peak
      systolic phase. CONCLUSIONS: We were able to demonstrate a compliance zone, which
      responds to pressure gradients, experimentally, in the form of a thin elastic
      region at an arterial bifurcation.

PMID- 24681854
TI  - The effect of respiratory and cardiac motion in liver diffusion tensor imaging
      (DTI).
AB  - OBJECTIVE: To evaluate the effect of respiratory and cardiac motion on diffusion
      tensor imaging (DTI) metrics in healthy human liver. METHODS: Fifteen healthy
      subjects, participating in either part of this study, were scanned using a 1.5-T
      magnetic resonance imaging (MRI) device. Coronal liver DTI (6 diffusion-encoding
      directions; b, 300 mm/s) during breath holding was compared to free breathing.
      Cardiac motion effects were evaluated by comparing breath-held DTI scans acquired
      during both diastole and systole. RESULTS: Free breathing resulted in a
      significantly increased mean diffusivity (P < 0.05), lambda1 (P < 0.01), lambda2
      (P < 0.05), and lambda3 (P < 0.01) compared to breath holding. During systole
      significant increases in fractional anisotropy (P < 0.05), mean diffusivity (P <
      0.05), and lambda1 (P < 0.05), compared to systole, were found in the left lobe.
      The right lobe, which is less affected by cardiac motion, showed no significant
      change in DTI metrics over the cardiac cycle. CONCLUSIONS: Respiratory and
      cardiac motion tends to increase liver DTI metrics.

PMID- 24681855
TI  - Role of whole-body magnetic resonance imaging in the evaluation of extrapulmonary
      tuberculosis in immunocompetent patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of whole-body magnetic
      resonance imaging (WB-MRI) in imaging of extrapulmonary tuberculosis. METHODS:
      Eighteen patients with single-site extrapulmonary tuberculosis were evaluated
      with contrast-enhanced dedicated MRI of the clinically symptomatic site followed
      by WB-MRI using contrast-enhanced 3-dimensional (3D) modified DIXON technique (m
      DIXON) and diffusion-weighted WB imaging with background body signal suppression
      (DWIBS) sequences. Studies were read by 2 experienced radiologists, and
      additional lesions seen on WB-MRI were separately charted. RESULTS: Of 18
      patients, 14 were found to have asymptomatic involvement of other organs on WB
      MRI. In 5 patients, the information was helpful in choosing an easily accessible
      site for biopsy/aspiration. Postcontrast 3D m-DIXON was better in picking up
      brain and lymph nodal lesions, whereas DWIBS was better in detecting vertebral
      lesions. CONCLUSIONS: Whole-body MRI may be used for assessing the asymptomatic
      involvement of other body organs in tuberculosis. The combination of postcontrast
      3D m-DIXON and DWIBS is complementary and may provide a road map for biopsy of
      accessible lesions.

PMID- 24681856
TI  - Good correlation of goutallier rating of supraspinatus fatty changes on axial and
      reformatted parasagittal computed tomographic images.
AB  - Traumatic tendon tear of the rotator cuff occurs frequently and leads to fatty
      muscle infiltration. With regard to the outcome, fatty infiltration of the
      rotator cuff muscles constitutes a major negative predictive factor after rotator
      cuff surgery. In 1989, Goutallier et al established his classification system for
      assessment of fatty infiltration of the rotator cuff muscles. He used computed
      tomographic (CT) images in the axial plane. Today, the assessment of rotator cuff
      muscles on axial CT images has been widely replaced by assessment on parasagittal
      acquired magnetic resonance images. This change raised 2 important questions.
      First, there is a controversy whether the Goutallier classification can simply be
      adopted for magnetic resonance imaging. The second question is whether the muscle
      assessment in the axial plane is interchangeable with that in the parasagittal
      plane. We hypothesize that the assessment of fatty muscle infiltration is the
      same on reformatted parasagittal CT images as on axial CT images METHODS: Three
      independent readers, 2 radiologists and one shoulder surgeon, rated fatty changes
      of the supraspinatus muscle on CT scans of 91 shoulders. Goutallier grades were
      assessed on axial and reformatted parasagittal CT images in 2 separate reading
      sessions. The paired t test was used to find differences between grading results
      on axial and reformatted parasagittal images. The Pearson correlation coefficient
      and weighted kappa statistics were used to quantify linear correlation,
      intrareader, and interreader agreement. RESULTS: Mean (SD) Goutallier grading
      among all readers was 0.80 (1.16) (range, 0-4) on axial images and 0.89 (1.05)
      (range, 004) on parasagittal reconstructions. We detected a trend toward a
      slightly higher Goutallier grading on parasagittal reconstructions; however, this
      result was not significant (P = 0.07). The Pearson correlation coefficient was
      0.702 (P < 0.001). Weighted kappa statistics indicated a moderately good to good
      intrareader (range of weighted kappa, 0.53-0.62) and interreader (weighted kappa,
      axial images, 0.55; reformatted parasagittal images, 0.65) agreement. CONCLUSION:
      Grading of fatty infiltration of the supraspinatus muscle on parasagittal CT
      images is comparable with the standard Goutallier grading on axial images and is
      characterized by a moderately good to good intrareader and interreader agreement.
      Assessment of parasagittal images is characterized by a slightly higher
      interreader agreement and may therefore be the preferable modality.

PMID- 24681857
TI  - Comparison of RECIST, mRECIST, and choi criteria for early response evaluation of
      hepatocellular carcinoma after transarterial chemoembolization using drug-eluting
      beads.
AB  - OBJECTIVE: To determine appropriate imaging criteria for early response
      evaluation in patients with hepatocellular carcinoma treated with transarterial
      chemoembolization (TACE) using drug-eluting beads. METHODS: Seventy-six patients
      who underwent TACE with drug-eluting beads as a first-line treatment were
      included. Responses at 1 month after treatment were evaluated by comparing
      contrast-enhanced computed tomography or magnetic resonance imaging performed
      before TACE. Evaluations were performed according to Response Evaluation Criteria
      in Solid Tumors (RECIST), modified RECIST (mRECIST), and Choi criteria.
      Correlation with progression-free survival (PFS) was compared using the Kaplan
      Meier method and log-rank test. RESULTS: Modified RECIST yielded a significant
      difference in PFS across the different response categories (P < 0.01); the Choi
      criteria exhibited a satisfactory difference in PFS, although the number of
      nonresponder patients was small (n = 5 [8.6%]). CONCLUSION: Application of
      mRECIST criteria at the 1-month follow-up computed tomography may be a reliable
      early predictor of outcome response in patients with hepatocellular carcinoma
      treated with TACE using drug-eluting beads.

PMID- 24681858
TI  - High spatial resolution, respiratory-gated, t1-weighted magnetic resonance
      imaging of the liver and the biliary tract during the hepatobiliary phase of
      gadoxetic Acid-enhanced magnetic resonance imaging.
AB  - PURPOSE: The aim of this study was to demonstrate the clinical feasibility of a
      recently developed navigator-gated, 3-dimensional gradient echo (3D-GRE) sequence
      for high-resolution, T1-weighted imaging (HR-T1WI) during the hepatobiliary phase
      (HBP) of gadoxetic acid-enhanced liver magnetic resonance imaging (MRI).
      MATERIALS AND METHODS: Eighty-seven consecutive patients who underwent gadoxetic
      acid-enhanced liver MRI were included in this study. To obtain HR-T1WI (acquired
      resolution, 1 * 1 * 2 mm), a gated 3D-GRE sequence (gated volumetric interpolated
      breath-hold examination [VIBE]; Siemens) with fat suppression was performed
      during the HBP and was then compared with standard breath-hold (BH)-GRE sequence
      (BH-VIBE). For the respiration gating, the phase ordering using the automatic
      window selection technique was used. Three readers independently scored the
      artifacts and the imaging quality (IQ) of both image sets and also classified BH
      VIBE images into acceptable or unacceptable IQ. Noise and signal-noise ratio of
      the BH-VIBE and gated-VIBE sequences were compared, and image quality improvement
      using gated VIBE compared with BH-VIBE was determined when BH-VIBE shows
      unacceptable IQ. RESULTS: The gated-VIBE sequence successfully provided HR-T1WI,
      having diagnosable image quality in all patients except 4 patients in 1 reader
      (95.4%, 83/87). The gated-VIBE sequence showed relatively higher levels of noise
      (mean [SD], 6.04 [3.18] vs. 3.57 [0.66]) but similar signal-noise ratio (93.60
      [39.47] vs. 100.05 [28.94]) compared with BH-VIBE (P = 0.15). In the qualitative
      analysis, the gated 3D-GRE sequence showed higher scores for depicting focal
      liver lesions and the sharpness of the hepatic edges (P < 0.0001) but lower
      subjective overall IQ than did the BH-VIBE (P < 0.01). However, in the patients
      showing unacceptable BH-VIBE image quality, the degree of improvement of the IQ
      using the gated-VIBE technique was significantly higher than that seen in the
      patients showing acceptable BH-VIBE image quality (P < 0.01). CONCLUSIONS: T1
      weighted gated-VIBE showed technical feasibility for HR-T1WI during HBP imaging
      of gadoxetic acid-enhanced MRI.

PMID- 24681859
TI  - The round window diameter in congenital aural atresia and comparison with
      sensorineural hearing loss and control group.
AB  - OBJECTIVE: The aim of this study was to measure round window (RW) diameters in
      patients with congenital aural atresia (CAA) or sensorineural hearing loss (SNHL)
      and a normal control group and to analyze whether differences exist between these
      groups. METHODS: Temporal bone computed tomographic scans of 12 patients with CAA
      (5 males, 7 females) aged 1 to 50 years (median age, 6 years), 12 patients with
      SNHL (8 males, 4 females) aged 2 to 32 years (median age, 5 years), and 11
      patients (3 males, 7 females) aged 2 months to 53 years (median age, 8 years)
      randomly selected from a pool of patients with unilateral chronic otitis media or
      cholesteatoma were reviewed. We measured RW diameter on oblique reconstruction
      planes. To prevent possible individual differences, skull width was measured.
      RESULTS: There were no statistically significant differences between all groups
      for skull width. Both RW diameter and RW membrane width were found smaller in the
      CAA group than both SNHL group and control group with statistical significance,
      whereas there were no statistically significant differences between the SNHL
      group and the control group. CONCLUSIONS: We found that both the RW diameter and
      RW membrane width in CAA were smaller than those in the control group. If this
      finding is supported in future studies, the production of floating mass
      transducer with different sizes may be useful. We suggest that RW diameter should
      be measured in each patient before operation and thus a floating mass transducer
      with the appropriate caliber should be chosen.

PMID- 24681860
TI  - A preliminary investigation of computed tomographic angiography in the assessment
      of coronary artery distensibility.
AB  - OBJECTIVE: To test 2 hypotheses: first, that coronary distensibility can be
      measured noninvasively using 64-slice computed tomographic angiography (CTA); and
      second, that the extent of coronary artery disease (CAD) in any individual
      patient is related to the degree of distensibility detected by CTA. MATERIALS AND
      METHODS: Computed tomographic angiography was performed in 30 healthy adults and
      in 30 patients. All subjects were younger than 55 years. The main lesion located
      in the left anterior descending branch in patients with CAD. The cross-sectional
      coronary area of the left main and the left anterior descending arteries were
      measured in each phase (5%-95%, 10% each), and any change in the ratio was
      quantified. A distensibility value (D value) was determined for each artery.
      RESULTS: Compared with healthy subjects, the coronary area of the patients with
      CAD was significantly decreased in 65% to 85% (P < 0.05). There was a significant
      difference in the D value between healthy subjects and patients with both single
      vessel and 2-vessel disease (P < 0.05). CONCLUSIONS: Coronary artery
      distensibility can be measured noninvasively using data obtained from CTA. The
      distensibility of the coronary artery decreased with the increasing number of
      involved pathological coronary vessels. The distensibility of the coronary artery
      correlated with the extent of CAD.

PMID- 24681861
TI  - Can full-dose contrast-enhanced CT be omitted from an FDG-PET/CT staging
      examination in newly diagnosed FDG-avid lymphoma?
AB  - OBJECTIVE: To determine whether full-dose contrast-enhanced computed tomography
      (CT) (CECT) can be omitted from an F-fluoro-2-deoxy-D-glucose (FDG) positron
      emission tomography (PET) (FDG-PET)/CT staging examination in newly diagnosed FDG
      avid lymphoma. METHODS: Twenty-nine patients with newly diagnosed FDG-avid
      lymphoma prospectively underwent unenhanced low-dose FDG-PET/CT and CECT.
      Different observers evaluated unenhanced low-dose FDG-PET/CT and CECT in a
      blinded manner. Ann Arbor stages according to unenhanced low-dose FDG-PET/CT and
      CECT were compared, and discrepancies between the 2 imaging modalities were
      resolved using bone marrow biopsy and posttreatment FDG-PET/CT as reference
      standard. Finally, it was assessed as to how many cases therapy would have been
      changed based on additional CECT findings. RESULTS: In 27 of 29 patients (93%;
      95% confidence interval, 78%-98%), CECT either did not change or did not
      correctly change the Ann Arbor stage that was assigned according to unenhanced
      low-dose FDG-PET findings. In 2 of 29 patients (7%; 95% confidence interval, 2%
      22%), CECT correctly provided another Ann Arbor stage than unenhanced low-dose
      FDG-PET/CT. In the latter 2 cases, therapy would not have been changed based on
      additional CECT findings. CONCLUSIONS: Unenhanced low-dose FDG-PET/CT alone is
      suggested as the primary imaging modality of choice for staging patients with
      newly diagnosed FDG-avid lymphoma. This diagnostic approach is particularly
      indicated in younger patients in whom diagnostic radiation exposure should be
      minimized and in patients who are at increased risk of CT contrast-induced
      allergic reactions or nephropathy.

PMID- 24681862
TI  - Calcium score: semiautomatic calculation using different vendors versus fully
      automatic software.
AB  - OBJECTIVES: Recent advances in technology have resulted in a multitude of cardiac
      imaging postprocessing software products from vendors unrelated to the scanner on
      which the cardiac study was initially performed. A fully automatic calcium score
      software has also become available. We assess the intervendor variability of
      calcium score measurement using the semiautomatic software provided by the
      scanner vendor versus an unrelated vendor versus fully automatic software.
      METHODS: All consecutive patients who had a calcium score performed from March
      2007 to January 2008 were included in this study. The studies were performed on
      two 64-slice computed tomographic scanners from 2 different vendors. The
      allocation of the patient to the specific scanner was done according to scanner
      and technologist availability. The studies were read twice by a cardiac
      radiologist and a general radiologist with at least 3 months' interval at a
      workstation specified by the computed tomographic scanner vendor and then at an
      unrelated workstation, with semiautomatic software. Calcium score was also
      independently performed by the fully automatic software, blinded to the results
      of previous readings. Agreement was tested with Pearson correlation coefficient,
      Bland-Altman graphs, and the Fleiss kappa test. RESULTS: The study population
      included 101 patients: 70 patients scanned at 1 scanner and 31 at a different
      scanner. Intervendor variability for the 2 groups had kappa = 0.98 +/- 0.01 and
      kappa = 0.96 +/- 0.02; interobserver variability had kappa = 1. Semiautomatic
      versus automatic variability showed kappa = 0.88 to 0.94. CONCLUSIONS: Because of
      very strong agreement between the calcium score measurements obtained by
      semiautomatic and fully automatic software by different vendors, calcium score
      measurements can be performed robustly at vendor-specific software, nonrelated
      software, or fully automatic software.

PMID- 24681863
TI  - Initial performance evaluation of iterative model reconstruction in abdominal
      computed tomography.
AB  - OBJECTIVE: The aim of this study was to present initial evaluation of the
      performance of the iterative model reconstruction algorithm (IMR) in abdominal
      computed tomography (CT). METHODS: Computed tomographic examinations were
      performed for clinical study of 36 patients and for phantom study. We
      reconstructed the raw data with 1.0- and 5.0-mm slice thicknesses using filtered
      back projection (FBP), iDose4, and IMR and evaluated image quality objectively
      and subjectively. RESULTS: For almost all subjective characteristics, the image
      quality was better using IMR than iDose4. Objective image noise was significantly
      less using IMR than iDose4 (P < 0.0001). The contrast-noise ratio of both slice
      thicknesses increased in order from FBP to iDose4 to IMR. The spatial resolution
      of reconstructed images was almost identical using IMR, FBP, and iDose4.
      CONCLUSIONS: The IMR can significantly improve image noise and low-contrast
      resolution and maintain edge sharpness in abdominal CT images compared with
      iDose4 or FBP.

PMID- 24681865
TI  - The combined effect of multidetector-row computed tomographic tube voltage, tube
      current, and image reconstruction algorithm on the detection of pneumothorax
      after intervention.
AB  - OBJECTIVES: The objective of the study was to determine the lowest multidetector
      row computed tomographic radiation dose parameters for the detection of
      pneumothorax after thoracic intervention. MATERIALS AND METHODS: An
      anthropomorphic chest phantom containing pneumothoraces was imaged with different
      tube voltages (80, 100, and 120 kV[p]) and tube currents (10, 20, 40, 75, and 110
      mAs). The images were reconstructed with both filtered back projection (FBP) and
      iterative reconstruction (IR) algorithms. Two blinded radiologists scored images
      independently for the presence or absence of pneumothorax. Effective dose, image
      noise, contrast-to-noise ratio, and signal-to-noise ratio were recorded. RESULTS:
      At radiation dose below 0.48 mSv, sensitivity for the detection of pneumothorax
      decreased in both reconstruction algorithms (80% for FBP vs 83% for IR; P >
      0.05). Interobserver agreement was good (k = 0.78). The IR data sets showed lower
      image noise as well as higher signal-to-noise ratio and contrast-to-noise ratio
      when compared with FBP on all acquisition parameters (P < 0.0001). CONCLUSIONS:
      Very low computed tomographic dose parameters may be suitable for confident
      detection of small pneumothoraces after intervention.

PMID- 24681864
TI  - Imaging features of growing teratoma syndrome following a malignant ovarian germ
      cell tumor.
AB  - OBJECTIVE: To access imaging findings of growing teratoma syndrome (GTS), which
      is a rare complication of malignant ovarian germ cell tumor (GCT) after
      chemotherapy. METHODS: Five patients met the criteria for GTS. Computed
      tomography and magnetic resonance images were retrospectively reviewed by 2
      radiologists in consensus for margin, attenuation, and the presence of gross fat
      or calcification of GTS lesions, which were compared with primary GCTs regarding
      tumor composition. RESULTS: Growing teratoma syndrome lesions were characterized
      as follows: poorly circumscribed, diffuse peritoneal masses in 2 patients; well
      circumscribed, localized peritoneal masses in 1 patient, and ovarian masses in 2
      patients. Features more noticeable in GTS lesions were more prominent fatty
      components in 4 patients and purely cystic lesion in 1 patient. CONCLUSIONS:
      Growing teratoma syndrome can be manifested as intraperitoneal masses with an
      increased fatty or cystic component. Radiologists should consider GTS when there
      are such masses on follow-up imaging studies in patients with malignant ovarian
      GCT.

PMID- 24681866
TI  - CT of preoperative and postoperative acetabular fractures revisited.
AB  - OBJECTIVE: We compared preoperative and postoperative computed tomography (CT)
      versus radiographic imaging in the evaluation of acetabular fractures (AFs).
      METHODS: Fifty-four patients who underwent imaging for AFs were retrospectively
      evaluated. Postoperative reduction quality was assessed on radiographs and CT
      scan by 2 observers. Rate of reintervention was noted. Radiation exposure from CT
      was calculated. RESULTS: After reduction, 24 patients had significant findings on
      postoperative CT. Five patients required reintervention, all of whom had
      significant postoperative CT findings and complex fractures. Notably, only 1 of
      the 5 patients had an indication for reintervention based on radiographs
      alone.The average dose for preoperative/postoperative CT study was 11.5/12.3 mSv,
      respectively, with a cumulative average dose of 23.8 mSv. CONCLUSIONS: Although
      reoperation rate is low after fixation of AFs, CT is required to identify those
      requiring reintervention. However, postoperative CT should be used judicially,
      only in patients presenting with complex acetabular fractures.

PMID- 24681867
TI  - Clinical application and diagnostic value of noninvasive spinal angiography in
      spinal vascular malformations.
AB  - OBJECTIVE: The purpose of this study was to explore the value of computed
      tomographic (CT) spinal angiography with 256-slice CT and fast dynamic contrast
      enhanced 3-dimensional magnetic resonance angiography (MRA) at 3.0 T in the
      diagnosis of spinal vascular malformations. METHODS: Seventeen patients who
      presented with suspected spinal vascular diseases by initial magnetic resonance
      and clinical findings all underwent CT spinal angiography. Among these, 10
      patients underwent MRA, 15 patients underwent digital subtraction angiography
      (DSA) within 3 to 5 days, and 8 patients finally underwent surgical treatment.
      RESULTS: Computed tomographic angiography examination clearly showed the abnormal
      vascular lesions in 16 of the 17 patients, including 7 patients with the
      diagnosis of spinal dural arteriovenous fistula, 7 patients with perimedullary
      arteriovenous fistula, and 2 patients with spinal arteriovenous malformations.
      The results were consistent with the diagnosis of DSA or surgery. One patient was
      poorly diagnosed. The fistulas could be seen in 12 patients; feeding arteries
      were correctly displayed in 12 patients. The fistulas and feeding arteries were
      accurately shown in 7 of 10 patients by MRA; DSA results were also negative in
      the other 3 patients. CONCLUSIONS: Spinal angiography with 256-slice CT and
      contrast-enhanced MRA at 3.0 T can clearly show the extent of spinal vascular
      malformations, feeding arteries, and fistulas. They are safe, noninvasive, as
      well as rapid and can shorten the time of DSA diagnosis and treatment.

PMID- 24681869
TI  - Diffusion tensor imaging of the normal foot at 3 T.
AB  - OBJECTIVE: The objective of this study was to establish normative diffusion
      tensor imaging (DTI) eigenvalues (lambda1,lambda2,lambda3), apparent diffusion
      coefficient, and fractional anisotropy in asymptomatic foot muscles. METHODS: Ten
      healthy adults (mean [SD], 25.9 [4.3] years) were examined using a 3-T magnetic
      resonance imaging scanner. Diffusion tensor imaging indices were evaluated in 5
      muscles in the foot: quadratus plantae, abductor hallucis, flexor hallucis
      brevis, flexor digitorum brevis, and abductor digiti minimi. Signal-to-noise
      ratio was also measured for each muscle. RESULTS: In the various foot muscles,
      lambda1 ranged from 1.88 * 10 to 2.14 * 10 mm/s, lambda2 ranged from 1.39 * 10 to
      1.48 * 10 mm/s, and lambda3 ranged from 0.91 * 10 to 1.27 * 10 mm/s; apparent
      diffusion coefficient ranged from 1.48 * 10 to 1.55 * 10 mm/s; and fractional
      anisotropy ranged from 0.21 to 0.40. Statistical differences were seen in some
      eigenvalues between muscle pairs. Mean signal-to-noise ranged from 47.5 to 69.1
      in the various muscles examined. CONCLUSIONS: Assessment of anisotropy of water
      diffusion in foot muscles was feasible using DTI. The measured DTI metrics in the
      foot were similar to those in calf and thigh skeletal muscles.

PMID- 24681868
TI  - Bony landmarks on computed tomographic localizer radiographs to prescribe a
      reduced scan range in patients undergoing multidetector computed tomography for
      suspected urolithiasis.
AB  - OBJECTIVE: The objective of this study was to determine bony landmarks that can
      be used on computed tomographic (CT) localizer radiographs to prescribe a reduced
      scan range for noncontrast CT (NCCT) for suspected urolithiasis. METHODS: This
      retrospective review comprised 243 patients who underwent NCCT for suspected
      urolithiasis. Scout line mode was used to correlate axial images with the z-axis
      location on CT localizer radiographs. The most inferior vertebral body end plate
      (superior or inferior) that was above the superiormost aspect of the highest
      kidney was recorded. The superior or inferior border of the pubic symphysis was
      determined to be below the inferiormost aspect of the bladder. The CT studies
      were then viewed to identify any findings that would be missed above or below the
      defined bony landmarks. RESULTS: Using the top or bottom of T10 included both
      kidneys in their entirety in 243 (100%) of 243 cases. Using the top or bottom of
      T11 included both kidneys in 241 (99%) of the 243 and 189 (78%) of the 243 cases,
      respectively. Using the top or bottom of the pubic symphysis included the entire
      bladder in 158 (65%) of the 243 and 243 (100%) of the 243 cases, respectively.
      The mean reduction in scan length was 5.17 cm (11.3%) above the bottom of T10 and
      2.89 cm (6.3%) below the pubic symphysis, for a total reduction of 8.06 cm
      (17.7%). CONCLUSIONS: Reducing the scan length is an effective technique to
      reduce radiation dose in patients undergoing NCCT for suspected urolithiasis. The
      bottom of T10 and the bottom of the pubic symphysis should be used as landmarks
      on the CT localizer radiograph.

PMID- 24681870
TI  - Liver computed tomography with low tube voltage and model-based iterative
      reconstruction algorithm for hepatic vessel evaluation in living liver donor
      candidates.
AB  - OBJECTIVE: The objective of this study was to investigate the image quality and
      diagnostic performance of model-based iterative reconstruction (MBIR) for hepatic
      vessel evaluation on low-tube-voltage (100 kilovolt [peak]) liver computed
      tomography (CT) for living donors. METHODS: Fifty-one liver donor candidates (low
      kilovolt group) underwent low-tube-voltage CT, which was reconstructed using
      filtered back projection, adaptive statistical iterative reconstruction, and
      MBIR. Additional 51 donor candidates who underwent 120-kilovolt (peak) CT using
      FBP were selected as matching control (standard group). The volume CT dose index,
      image noise, contrast-to-noise ratios, diagnostic accuracy, and confidence of
      hepatic vasculatures were evaluated. RESULTS: Significant dose reduction was
      obtained with low-tube-voltage CT. The MBIR images of the low-kilovolt group
      showed significantly lower image noise and higher contrast-to-noise ratios than
      did the other image sets (P < 0.001). Regarding diagnostic accuracy and
      confidence of hepatic vessel anatomic variations with surgical correlation, the
      MBIR images provided results equivalent to those of other images (P > 0.05).
      CONCLUSIONS: Low-tube-voltage liver CT using MBIR may increase image quality and
      preserve diagnostic performance of hepatic vessel evaluation at reduced radiation
      dose.

PMID- 24681871
TI  - Adaptive genetic divergence along narrow environmental gradients in four stream
      insects.
AB  - A central question linking ecology with evolutionary biology is how environmental
      heterogeneity can drive adaptive genetic divergence among populations. We
      examined adaptive divergence of four stream insects from six adjacent catchments
      in Japan by combining field measures of habitat and resource components with
      genome scans of non-neutral Amplified Fragment Length Polymorphism (AFLP) loci.
      Neutral genetic variation was used to measure gene flow and non-neutral genetic
      variation was used to test for adaptive divergence. We identified the
      environmental characteristics contributing to divergence by comparing genetic
      distances at non-neutral loci between sites with Euclidean distances for each of
      15 environmental variables. Comparisons were made using partial Mantel tests to
      control for geographic distance. In all four species, we found strong evidence
      for non-neutral divergence along environmental gradients at between 6 and 21 loci
      per species. The relative contribution of these environmental variables to each
      species' ecological niche was quantified as the specialization index, S, based on
      ecological data. In each species, the variable most significantly correlated with
      genetic distance at non-neutral loci was the same variable along which each
      species was most narrowly distributed (i.e., highest S). These were gradients of
      elevation (two species), chlorophyll-a, and ammonia-nitrogen. This adaptive
      divergence occurred in the face of ongoing gene flow (Fst = 0.01-0.04),
      indicating that selection was strong enough to overcome homogenization at the
      landscape scale. Our results suggest that adaptive divergence is pronounced,
      occurs along different environmental gradients for different species, and may
      consistently occur along the narrowest components of species' niche. 

PMID- 24681873
TI  - Hydrothermal synthesis, structure and magnetic properties of a three-dimensional
      cobalt(II) - aminophenyltetrazolate coordination polymer.
AB  - The hydrothermal reaction of cobalt(II) acetate tetrahydrate, 4-aminophenyl
      tetrazole and water at 135  degrees C for 48 hours provided orange crystals of
      [Co3(OH)2(H2O)2(aptet)4] (1) (aptet = 4-aminophenyltetrazolate). The three
      dimensional structure of compound 1 is constructed from chains of corner- and
      edge-sharing Co(II) octahedra linked into a framework through the dipodal ligand
      tethers. The cobalt sites of the chain are linked through tetrazolate groups in
      the N2,N3-bridging mode, as well as through MU3-hydroxyl groups into trinuclear
      Co3 substructures. The magnetic properties are consistent with a ferrimagnetic
      chain with the non-compensating resultant moment of one Co(II) per trinuclear
      Co(II) subunit. The temperature dependence of the ac magnetic susceptibility
      indicates glassy-like magnetic behavior.

PMID- 24681872
TI  - Candesartan induces a prolonged proangiogenic effect and augments endothelium
      mediated neuroprotection after oxygen and glucose deprivation: role of vascular
      endothelial growth factors A and B.
AB  - Angiogenesis is a key component of recovery after stroke. Angiotensin II receptor
      blocker (ARB) treatment improves neurobehavioral outcome and is associated with
      enhanced angiogenesis after stroke. The purpose of this study is to investigate
      the temporal pattern of the ARB proangiogenic effect in the ischemic brain and
      its association with vascular endothelial growth factors VEGF-A and VEGF-B.
      Wistar rats were exposed to 90-minute middle cerebral artery occlusion and
      treated with candesartan (1 mg/kg) at reperfusion. The proangiogenic potential of
      the cerebrospinal fluid was determined at 8, 24, 48, and 72 hours using an in
      vitro Matrigel tube formation assay. In addition, the expression of VEGF-A and
      VEGF-B was measured in brain homogenates using Western blotting at the same time
      points. A single candesartan dose induced a prolonged proangiogenic effect and a
      prolonged upregulation of VEGF-A and VEGF-B in vivo. In the ischemic hemisphere,
      candesartan treatment was associated with stabilization of hypoxia-inducible
      factor-1alpha and preservation of angiopoietin-1. The effect of ARB treatment on
      endothelial cells was studied in vitro. Our results identified brain endothelial
      cells as one target for the action of ARBs and a source of the upregulated VEGF-A
      and VEGF-B, which exerted an autocrine angiogenic response, in addition to a
      paracrine neuroprotective effect. Taken together, this study highlights the
      potential usefulness of augmenting the endogenous restorative capacity of the
      brain through the administration of ARBs. 

PMID- 24681875
TI  - Can statistically determined prognostic factors predict the long-term survival of
      patients with pancreatic ductal adenocarcinoma following surgical resection?:
      Clinicopathological analysis of 82 long-term survivors.
AB  - OBJECTIVE: The objective of this study were to analyze and describe the
      clinicopathological characteristics of long-term pancreatic ductal adenocarcinoma
      survivors and to determine if statistically identified prognostic factors can be
      used to predict the actual survival. METHODS: Between January 2000 and December
      2007, 537 patients with resectable pancreatic ductal adenocarcinoma underwent
      surgical resection at a single institute. Medical records were retrospectively
      reviewed, and 9 patients were excluded. Of the remaining 528, patients who
      survived for more than 5 years were classified as long-term survivors. RESULTS:
      The actual 5-year survival rate of all 528 included patients was 15.5% (82
      patients; median follow-up period, 82.7 months). Fifty-eight patients (70.7%)
      were diagnosed with cancers located in the head of pancreas, and the median size
      was 2.5 cm (range, 0.8-12.0 cm). Three patients had focal involvement noted on
      the resected surfaces. Poorly differentiated carcinoma (9.8%), lymph node
      metastasis (32.9%), lymphovascular invasion (25.6%), and perineural invasion
      (48.8%) were detected. Fifty-five of the 82 long-term survivors whose
      clinicopathological characteristics included several dismal predictors survived
      for more than 5 years without recurrence. CONCLUSIONS: The long-term survivors
      identified in this study did not meet the appropriate prognostic criteria.
      Therefore, there are limitations in the use of statistically determined
      prognostic factors for estimating in the long term.

PMID- 24681874
TI  - KRAS mutations in codon 12 or 13 are associated with worse prognosis in
      pancreatic ductal adenocarcinoma.
AB  - OBJECTIVE: Mutations in the KRAS and P53 genes belong to the most frequently
      observed genetic alterations in pancreatic ductal adenocarcinoma. The aim of this
      study was to examine the frequency and prognostic impact of KRAS mutations. In
      addition, we attempted to define molecular subgroups with distinct biologic
      behavior by combination of KRAS sequencing data with p53 protein expression data.
      METHODS: KRAS mutational analyses were performed in a study group of 153 patients
      by Sanger sequencing. Immunohistochemistry for p53 was performed on tissue
      microarrays. RESULTS: KRAS mutations in codon 12 or 13 were found in 68% of
      cases. Nuclear staining for p53 was detectable in 110 (68%) of 162 evaluable
      cases. We found no correlation between KRAS mutational status and p53 expression.
      KRAS mutational status but not p53 immunohistochemistry was an independent
      prognostic factor in the study group (P = 0.02). In a stratified analysis
      according to KRAS mutational status, p53 expression failed to define prognostic
      groups beyond the impact of KRAS mutational status. CONCLUSIONS: Our results
      support the crucial role of KRAS mutational status in pancreatic cancer biology.
      KRAS mutational status may serve as a prognostic marker. However, its predictive
      role for targeted therapies remains to be evaluated.

PMID- 24681876
TI  - A population-based evaluation of readmissions after first hospitalization for
      acute pancreatitis.
AB  - OBJECTIVE: This study aimed to evaluate the burden and pattern of pancreatitis
      related readmissions after index hospitalization for acute pancreatitis (AP).
      METHODS: We identified all unique white or black Allegheny County residents with
      first hospital admission for AP from 1996 to 2005 using the Pennsylvania Health
      Care Cost Containment Council data set. The final study population consisted of
      patients (n = 6010) who survived index admission and had follow-up data on
      readmissions. The etiology was determined using associated diagnosis codes. We
      analyzed pancreatitis-related readmissions until the third quarter of 2007
      (median follow-up time, 39 months). RESULTS: The absolute risk and total burden
      of readmissions were 21.9% and 2947 for primary AP, respectively, 5.8% and 812
      for primary chronic pancreatitis (CP), respectively, and 32.3% and 6612 for any
      pancreatitis diagnosis, respectively. Patients with alcohol etiology (etiology on
      index admission in 20.3%; responsible for 41.6%-50.4% readmissions) and
      subsequent diagnosis of CP (any CP diagnosis, 12.8%; responsible for 73%
      readmissions) accounted for a disproportionately higher fraction of readmissions.
      Readmission risk decreased with increasing age. A small fraction of patients
      accounted for most readmissions. CONCLUSIONS: Readmission after AP is influenced
      by demographics, etiology, and subsequent CP diagnosis. Future studies should
      focus on understanding the factors driving readmissions in high-risk individuals
      to develop strategies for reducing pancreatitis-related readmissions and health
      care costs.

PMID- 24681878
TI  - Retrospective comparison between preoperative diagnosis by International
      Consensus Diagnostic Criteria and histological diagnosis in patients with focal
      autoimmune pancreatitis who underwent surgery with suspicion of cancer.
AB  - OBJECTIVE: The objective of this study was to compare the preoperative diagnosis
      by International Consensus Diagnostic Criteria (ICDC) with histological diagnosis
      in patients with focal autoimmune pancreatitis (AIP) who underwent surgery.
      METHODS: Thirty patients (type 1 AIP in 23 and type 2 AIP in 7) with a diagnosis
      of AIP based on histology of surgical specimens were classified according to ICDC
      based on their preoperative data. RESULTS: Pancreatic core biopsies and
      diagnostic steroid trial were not preoperatively performed in any of the
      patients. Based on preoperative data, ICDC diagnosed 6 patients (20%) as having
      type 1 AIP and 24 (80%) as probable AIP. Assuming all patients had responded to a
      steroid trial preoperatively, ICDC would have diagnosed 8 patients (27%) as
      having type 1 AIP, 4 (13%) as type 2 AIP, 10 as AIP-not otherwise specified
      (33%), and 8 (27%) as probable AIP. In the hypothetical situation, 7 of 8 type 1
      AIP patients and 3 of 3 type 2 AIP patients would have been classified into the
      correct subtype of AIP. CONCLUSIONS: A steroid trial enhances the possibility of
      correctly diagnosing AIP by ICDC despite the lack of histology. However, some
      patients cannot be diagnosed as having AIP or be classified into the correct
      subtype without histology.

PMID- 24681879
TI  - Does the presence of obesity and/or metabolic syndrome affect the course of acute
      pancreatitis?: A prospective study.
AB  - OBJECTIVE: The incidence of acute pancreatitis (AP) is rising with increased
      prevalence of obesity, which exacerbates pancreatic injury. Metabolic syndrome
      (MS) is defined as a cluster condition of cardiovascular risk factors, including
      hyperglycemia, dyslipidemia, hypertension, and central obesity. We analyze if the
      presence of obesity and/or MS affects the course of pancreatitis. METHODS: Data
      were collected from 140 patients with AP between January 2010 and February 2013.
      Anthropometric data, including body mass index and waist circumference, were
      measured. Biochemical tests were used including fasting glucose, triglyceride,
      low- and high-density lipoprotein cholesterol levels, and total cholesterol
      level. Atlanta criteria, Acute Physiology and Chronic Health Evaluation II, and
      Ranson scoring system were used to define severe AP. Patients were classified as
      having MS based on the International Diabetic Federation criteria. RESULTS: The
      mean body mass index was 30.15 kg/m(2). Sixteen (11.4%) patients had severe AP,
      whereas 124 (88.6%) patients had mild AP. We found that 62.8% of patients with AP
      fulfilled the criteria of MS (P = 0.000). Body weight can be used to predict
      clinical severity of AP with significant P value (P = 0.009). CONCLUSIONS: The
      presence of MS in patients with pancreatitis is noticeable, but it does not
      affect the course of disease severity, whereas obesity correlates with
      pancreatitis severity.

PMID- 24681877
TI  - Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas and acute and
      chronic pancreatitis and effect of their activation by a CX3CR1 agonist.
AB  - OBJECTIVES: Numerous studies suggest important roles of the chemokine,
      fractalkine (CX3CL1), in acute/chronic pancreatitis; however, the possible
      mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play
      important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as
      well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1)
      occurrence in normal pancreas and pancreatitis (acute/chronic) tissues and the
      effects of CX3CL1 on activated PSCs. METHODS: CX3CR1 expression/localization in
      normal pancreas and pancreatitis (acute/chronic) tissues was evaluated with
      immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on
      activated PSCs were examined with real-time polymerase chain reaction, BrdU (5
      bromo-2-deoxyuridine) assays, and Western blotting. RESULTS: In normal pancreas,
      acinar cells expressed CX3CR1 within granule-like formations in the cytoplasm,
      whereas in acute/chronic pancreatitis, acinar, ductal, and activated PSCs
      expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is
      increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1 did not
      induce inflammatory genes expression in activated PSCs, but induced
      proliferation. CONCLUSIONS: CX3CR1s are expressed in normal pancreas. Expression
      is increased in acute/chronic pancreatitis, and the CX3CR1s are activated. CX3CL1
      induces proliferation of activated PSCs without increasing release of
      inflammatory mediators. These results suggest that CX3CR1 activation of PSCs
      could be important in their effects in pancreatitis, especially to PSC
      proliferation in pancreatitis where CX3CL1 levels are elevated.

PMID- 24681881
TI  - The key residue for SSB-RecO interaction is dispensable for Deinococcus
      radiodurans DNA repair in vivo.
AB  - The RecFOR DNA repair pathway is one of the major RecA-dependent recombinatorial
      repair pathways in bacteria and plays an important role in double-strand breaks
      repair. RecO, one of the major recombination mediator proteins in the RecFOR
      pathway, has been shown to assist RecA loading onto single-stranded binding
      protein (SSB) coated single-stranded DNA (ssDNA). However, it has not been
      characterized whether the protein-protein interaction between RecO and SSB
      contributes to that process in vivo. Here, we identified the residue arginine-121
      of Deinococcus radiodurans RecO (drRecO-R121) as the key residue for RecO-SSB
      interaction. The substitution of drRecO-R121 with alanine greatly abolished the
      binding of RecO to SSB but not the binding to RecR. Meanwhile, SSB-coated ssDNA
      annealing activity was also compromised by the mutation of the residue of drRecO.
      However, the drRecO-R121A strain showed only modest sensitivity to DNA damaging
      agents. Taking these data together, arginine-121 of drRecO is the key residue for
      SSB-RecO interaction, which may not play a vital role in the SSB displacement and
      RecA loading process of RecFOR DNA repair pathway in vivo. 

PMID- 24681882
TI  - A multi-epitope vaccine based on Chlamydia trachomatis major outer membrane
      protein induces specific immunity in mice.
AB  - We evaluated the immunogenicity and efficacy of a candidate vaccine comprising
      the major outer membrane protein (MOMP) multi-epitope of Chlamydia trachomatis. A
      short gene of multi-epitope derived from MOMP containing multiple T- and B-cell
      epitopes was artificially synthesized. The recombinant plasmid pET32a(+)
      containing codon optimized MOMP multi-epitope gene was constructed. Expression of
      the fusion protein Trx-His-MOMP multi-epitope in Escherichia coli was confirmed
      by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot
      analysis. Balb/c mice were inoculated with the purified fusion protein
      subcutaneously three times with 2-week intervals. Results showed that the MOMP
      multi-epitope elicited not only strong humoral immune responses to C. trachomatis
      by generating significantly high levels of specific antibodies (IgG1 and IgG2a),
      but also a cellular immune response by inducing robust cytotoxic T lymphocyte
      responses in mice. Furthermore, the MOMP multi-epitope substantially primed
      secretion of IFN-gamma, revealing that this vaccine could induce a strong Th1
      response. Finally, the mice vaccinated with the MOMP multi-epitope displayed a
      reduction of C. trachomatis shedding upon a chlamydial challenge and an
      accelerated clearance of the infected C. trachomatis. In conclusion, the MOMP
      multi-epitope vaccine may have the potentiality for the development of effective
      prophylactic and therapeutic vaccines against the C. trachomatis infection. 

PMID- 24681880
TI  - Long-term function of islets encapsulated in a redesigned alginate microcapsule
      construct in omentum pouches of immune-competent diabetic rats.
AB  - OBJECTIVE: Our study aim was to determine encapsulated islet graft viability in
      an omentum pouch and the effect of fibroblast growth factor 1 (FGF-1) released
      from our redesigned alginate microcapsules on the function of the graft. METHODS:
      Isolated rat islets were encapsulated in an inner core made with 1.5% low
      viscosity-high-mannuronic-acid alginate followed by an external layer made with
      1.25% low-viscosity high-guluronic acid alginate with or without FGF-1, in
      microcapsules measuring 300 to 400 um in diameter. The 2 alginate layers were
      separated by a perm-selective membrane made with 0.1% poly-L-ornithine, and the
      inner low-viscosity-high-mannuronic-acid core was partially chelated using 55 mM
      sodium citrate for 2 minutes. RESULTS: A marginal mass of encapsulated islet
      allografts (~2000 islets/kg) in streptozotocin-diabetic Lewis rats caused
      significant reduction in blood glucose levels similar to the effect observed with
      encapsulated islet isografts. Transplantation of alloislets coencapsulated with
      FGF-1 did not result in better glycemic control, but induced greater body weight
      maintenance in transplant recipients compared with those that received only
      alloislets. Histological examination of the retrieved tissue demonstrated
      morphologically and functionally intact islets in the microcapsules, with no
      signs of fibrosis. CONCLUSIONS: We conclude that the omentum is a viable site for
      encapsulated islet transplantation.

PMID- 24681883
TI  - Prion protein and cancers.
AB  - The normal cellular prion protein, PrP(C) is a highly conserved and widely
      expressed cell surface glycoprotein in all mammals. The expression of PrP is
      pivotal in the pathogenesis of prion diseases; however, the normal physiological
      functions of PrP(C) remain incompletely understood. Based on the studies in cell
      models, a plethora of functions have been attributed to PrP(C). In this paper, we
      reviewed the potential roles that PrP(C) plays in cell physiology and focused on
      its contribution to tumorigenesis.

PMID- 24681884
TI  - Effect of Smac and Taxol on non-small-cell lung cancer.
AB  - A series of structurally unique second mitochondria-derived activator of caspases
      (Smacs) that act as antagonists of the inhibitor of apoptosis proteins (IAPs)
      directly have been discovered. They play crucial roles in mitochondrial apoptosis
      pathways and promote chemotherapy-induced apoptosis. In this study, we
      constructed a eukaryotic expression vector pcDNA3.1/Smac and transfected it into
      A549 human lung cancer cells. Then we analyzed the cell invasive and cloning
      ability, as well as cell apoptosis induced by Taxol. The results showed that over
      expressed Smac significantly inhibited A549 cell invasive and cloning ability and
      promoted apoptosis following Taxol treatment. This finding provides a potential
      approach for the biological therapy of lung cancer. 

PMID- 24681885
TI  - Circadian clock gene expression regulates cancer cell growth through glutaminase.
AB  - Glutamine is an essential amino acid for malignant tumor cells. Glutaminase that
      metabolizes glutamine reaches a maximum expression in tumors immediately before
      the maximum proliferation rate. Tumor cells grow at different rates during the
      day. We postulated that the activity of glutaminase in tumor cells is subject to
      the regulation of circadian clock gene. We measured glutaminase by western blot
      analysis and circadian clock gene expression by real-time polymerase chain
      reaction in the liver and tumor cells at six equispaced time points of the day in
      individual mice of a 12/12 h light/dark schedule. The results showed that the
      tumor-bearing mice, under normal diurnal conditions, are circadianly entrained,
      as reflected by the normal host locomotor activity rhythms and rhythmic liver
      clock gene expression. The tumors within these mice are also circadianly
      organized, as reflected by circadian clock gene (Bmal1) expression. What is most
      remarkable is that kidney-type glutaminase also showed circadian rhythms in the
      same pattern with tumor circadian clock gene expression in liver cancer xenograft
      model, indicating that conditionally inhibiting glutaminase activity may provide
      a new target for cancer therapy. 

PMID- 24681886
TI  - The retrovirus HERVH is a long noncoding RNA required for human embryonic stem
      cell identity.
AB  - Human endogenous retrovirus subfamily H (HERVH) is a class of transposable
      elements expressed preferentially in human embryonic stem cells (hESCs). Here, we
      report that the long terminal repeats of HERVH function as enhancers and that
      HERVH is a nuclear long noncoding RNA required to maintain hESC identity.
      Furthermore, HERVH is associated with OCT4, coactivators and Mediator subunits.
      Together, these results uncover a new role of species-specific transposable
      elements in hESCs. 

PMID- 24681888
TI  - Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative
      stress response and iron immunology.
AB  - The connection between gene regulation and metabolism is an old issue that
      warrants revisiting in order to understand both normal as well as pathogenic
      processes in higher eukaryotes. Metabolites affect the gene expression by either
      binding to transcription factors or serving as donors for post-translational
      modification, such as that involving acetylation and methylation. The focus of
      this review is heme, a prosthetic group of proteins that includes hemoglobin and
      cytochromes. Heme has been shown to bind to several transcription factors,
      including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the
      transcriptional repressor activity of Bach1, resulting in the derepression of its
      target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse
      cell types. Since Bach2 is important for class switch recombination and somatic
      hypermutation of immunoglobulin genes as well as regulatory and effector T cell
      differentiation and the macrophage function, the heme-Bach2 axis may regulate the
      immune response as a signaling cascade. We discuss future issues regarding the
      topic of the iron/heme-gene regulation network based on current understanding of
      the heme-Bach axis, including the concept of "iron immunology" as the synthesis
      of the iron metabolism and the immune response. 

PMID- 24681887
TI  - Global effects of the CSR-1 RNA interference pathway on the transcriptional
      landscape.
AB  - Argonaute proteins and their small RNA cofactors short interfering RNAs are known
      to inhibit gene expression at the transcriptional and post-transcriptional
      levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of
      endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts.
      However, its role in gene expression regulation remains controversial. Here we
      used genome-wide profiling of nascent RNA transcripts and found that the CSR-1
      RNA interference pathway promoted sense-oriented RNA polymerase II transcription.
      Moreover, a loss of CSR-1 function resulted in global increase in antisense
      transcription and ectopic transcription of silent chromatin domains, which led to
      reduced chromatin incorporation of centromere-specific histone H3. On the basis
      of these findings, we propose that the CSR-1 pathway helps maintain the
      directionality of active transcription, thereby propagating the distinction
      between transcriptionally active and silent genomic regions. 

PMID- 24681889
TI  - The common occurrence of epistasis in the determination of human pigmentation and
      its impact on DNA-based pigmentation phenotype prediction.
AB  - The role of epistatic effects in the determination of complex traits is often
      underlined but its significance in the prediction of pigmentation phenotypes has
      not been evaluated so far. The prediction of pigmentation from genetic data can
      be useful in forensic science to describe the physical appearance of an unknown
      offender, victim, or missing person who cannot be identified via conventional DNA
      profiling. Available forensic DNA prediction systems enable the reliable
      prediction of several eye and hair colour categories. However, there is still
      space for improvement. Here we verified the association of 38 candidate DNA
      polymorphisms from 13 genes and explored the extent to which interactions between
      them may be involved in human pigmentation and their impact on forensic DNA
      prediction in particular. The model-building set included 718 Polish samples and
      the model-verification set included 307 independent Polish samples and additional
      72 samples from Japan. In total, 29 significant SNP-SNP interactions were found
      with 5 of them showing an effect on phenotype prediction. For predicting green
      eye colour, interactions between HERC2 rs12913832 and OCA2 rs1800407 as well as
      TYRP1 rs1408799 raised the prediction accuracy expressed by AUC from 0.667 to
      0.697 and increased the prediction sensitivity by >3%. Interaction between MC1R
      'R' variants and VDR rs731236 increased the sensitivity for light skin by >1% and
      by almost 3% for dark skin colour prediction. Interactions between VDR rs1544410
      and TYR rs1042602 as well as between MC1R 'R' variants and HERC2 rs12913832
      provided an increase in red/non-red hair prediction accuracy from an AUC of 0.902
      0.930. Our results thus underline epistasis as a common phenomenon in human
      pigmentation genetics and demonstrate that considering SNP-SNP interactions in
      forensic DNA phenotyping has little impact on eye, hair and skin colour
      prediction. 

PMID- 24681890
TI  - Energy propagation throughout chemical networks.
AB  - In order to maintain their metabolism from an energy source, living cells rely on
      chains of energy transfer involving functionally identified components and
      organizations. However, propagation of a sustained energy flux through a cascade
      of reaction cycles has only been recently reproduced at a steady state in simple
      chemical systems. As observed in living cells, the spontaneous onset of energy
      transfer chains notably drives local generation of singular dissipative chemical
      structures: continuous matter fluxes are dynamically maintained at boundaries
      between spatially and chemically segregated zones but in the absence of any
      membrane or predetermined material structure. 

PMID- 24681891
TI  - Childhood adversity, recent life stressors and suicidal behavior in Chinese
      college students.
AB  - BACKGROUND: Although the independent effects of childhood adversities and of
      recent negative events on suicidality have been well-documented, the combinative
      role of childhood and recent adversities on risk for suicidality is still
      underexplored, especially in the context of Chinese culture and in consideration
      of specific types of negative events. METHOD: 5989 students, randomly sampled
      from six universities in central China, completed the online survey for this
      study. Suicidal behavior, life adversity during childhood and stressful events in
      recent school life were assessed with designed questionnaires. RESULTS: Students
      experiencing recent stressful life events more often reported an experience of
      life adversity during childhood. While recent stressful life events and childhood
      life adversity both were associated with an increased risk for suicidal behavior,
      the two exposures presented conjunctively and acted interactively to increase the
      risk. There was noticeable variation of effects associated with specific
      childhood life adversities, and sexual abuse, poor parental relationship, divorce
      of parents and loss of a parent were among the adversities associated with the
      highest increased risk. Recent conflicts with classmates, poor school performance
      and rupture of romantic relationships were the recent school life stressors
      associated with the highest increased risk. CONCLUSIONS: Childhood adversity and
      recent school life stressors had a combinative role in predicting suicidality of
      young people studying in Chinese colleges. Unhappy family life during childhood
      and recent interpersonal conflicts in school were the most important predictors
      of suicidality in this population.

PMID- 24681892
TI  - Biglycan enhances gastric cancer invasion by activating FAK signaling pathway.
AB  - Biglycan (BGN) is an important member of small leucine-rich proteoglycans family,
      and has been implicated in oncogenesis and development of various human cancer
      types. Here we report that BGN promotes tumor invasion and metastasis of gastric
      cancer both in vitro and in vivo. BGN expression is significantly higher in
      gastric cancer tissues and associated with lymph node metastasis, depth of tumor
      invasion and TNM stage. BGN enhances gastric cancer cell wound healing, migration
      and invasion ability as well as the tube formation ability of endothelial cells
      in vitro. Animal experiments results in vivo are consistent with outcomes in
      vitro. BGN induces increased phosphorylation of FAK (Tyr576/577, Tyr925 and
      Tyr397) and Paxillin. These results indicate that BGN is upregulated, and plays
      an oncogenic role, in gastric cancer metastasis by activating the FAK signaling
      pathway. 

PMID- 24681893
TI  - Pharmacological basis for the medicinal use of Wrightia tinctoria in hypertension
      and dyslipidemia.
AB  - This study was aimed to offer a possible pharmacological basis regarding the
      remedial utilization of Wrightia tinctoria in hypertension and dyslipidemia in
      certain South Asian traditional systems of medicine, using in vivo and in vitro
      assays. The aqueous methanolic extract of W. tinctoria seeds (Wt.Cr) caused a
      dose-dependent (1-10 mg/kg) decrease in arterial pressure in anesthetized rats.
      In the right atria of isolated guinea pigs, Wt.Cr equally inhibited force and
      rate of spontaneous atrial contractions. When tested on phenylephrine-, high K(+)
      , and low K(+)-induced vasoconstrictions in isolated rat aorta, Wt.Cr produced a
      concentration-dependent vasorelaxation, the most potent being against low K(+)
      induced contraction. It also created a rightward shift in the Ca(++)
      concentration-response curves and suppressed phenylephrine control peaks in a
      Ca(++)-free environment. In the rat model of tyloxapol-induced dyslipidemia,
      Wt.Cr produced a decline in the serum levels of total cholesterol and
      triglycerides. In high fat diet-induced dyslipidemia, it decreased serum total
      cholesterol and low-density lipoprotein cholesterol, improved high-density
      lipoprotein cholesterol, and prevented the increase in average body weights by
      causing a decrease in diet consumption. These data suggest that Wt.Cr(++) lowers
      blood pressure through a combination of K(+)-channel opening and Ca(++)-channel
      blocking effects along with antidyslipidemic and weight-reducing properties.

PMID- 24681895
TI  - Discovery of a novel inhibitor of NAD(P)(+)-dependent malic enzyme (ME2) by high
      throughput screening.
AB  - AIM: Malic enzymes are oxidative decarboxylases with NAD(+) or NAD(P)(+) as
      cofactor that catalyze the conversion of L-malate to pyruvate and CO2. The aim of
      this study was to discover and characterize a potent inhibitor of human NAD(P)(+)
      dependent malic enzyme 2 (ME2). METHODS: Recombinant human ME2-His-Tag fusion
      protein was overexpressed in E coli and purified with Ni-NTA resin. A high
      throughput screening (HTS) assay was developed to find ME2 inhibitors. Detergent
      Brij-35 was used to exclude false positives. The characteristics of the inhibitor
      were analyzed with enzyme kinetics analysis. A thermal shift assay for ME2 was
      carried out to verify the binding of the inhibitor with the enzyme. RESULTS: An
      HTS system for discovering ME2 inhibitors was established with a Z' factor value
      of 0.775 and a signal-to-noise ratio (S/N) of 9.80. A library containing 12 683
      natural products was screened. From 47 hits, NPD387 was identified as an
      inhibitor of ME2. The primary structure-activity relationship study on NPD387
      derivatives showed that one derivative NPD389 was more potent than the parent
      compound NPD387 (the IC50 of NPD389 was 4.63 +/- 0.36 MUmol/L or 5.59 +/- 0.38
      MUmol/L, respectively, in the absence or presence of 0.01% Brij-35 in the assay
      system). The enzyme kinetics analysis showed that NPD389 was a fast-binding
      uncompetitive inhibitor with respect to the substrate NAD(+) and a mixed-type
      inhibitor with respect to the substrate L-malate. CONCLUSION: NPD389 is a potent
      ME2 inhibitor that binds to the enzyme in a fast-binding mode, acting as an
      uncompetitive inhibitor with respect to the substrate NAD(+) and a mixed-type
      inhibitor with respect to the substrate L-malate.

PMID- 24681897
TI  - Effects of a sucrose-enriched diet on the pattern of gene expression, contraction
      and Ca(2+) transport in Goto-Kakizaki type 2 diabetic rat heart.
AB  - There has been a spectacular rise in the global prevalence of type 2 diabetes
      mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and
      mortality in diabetic patients. A variety of diastolic and systolic dysfunctions
      have been demonstrated in type 2 diabetic heart. The consumption of sugar
      sweetened beverages has been linked to rising rates of obesity, which in turn is
      a risk factor for development of T2DM. In this study, the effects of a sucrose
      enriched diet on the pattern of gene expression, contraction and Ca(2+) transport
      in the Goto-Kakizaki T2DM rat heart were investigated. Genes encoding cardiac
      muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), intercellular proteins
      (Gja4), cell membrane transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and
      Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding
      potassium channels (Kcnb1) were downregulated in GK compared with control rats.
      Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), intercellular
      proteins (Gja1 and Gja4), intracellular Ca(2+) transport (Atp2a1 and Ryr2), cell
      membrane transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and
      Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were
      downregulated in control rats fed sucrose compared with control rats. Genes
      encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11)
      were downregulated in control and GK rats fed sucrose compared with control and
      GK rats, respectively. The amplitude of shortening was reduced in myocytes from
      the control-sucrose group compared with control rats and in the GK-sucrose group
      compared with GK rats. The amplitude of the Ca(2+) transient was increased in
      myocytes from control-sucrose compared with control rats and decreased in GK
      sucrose compared with GK rats. Subtle alterations in the pattern of expression of
      genes encoding a variety of cardiac muscle proteins are associated with changes
      in shortening and intracellular Ca(2+) transport in ventricular myocytes from GK
      T2DM and control rats fed a sucrose-enriched diet.

PMID- 24681896
TI  - Discovery and characterization of novel small molecule agonists of G protein
      coupled receptor 119.
AB  - AIM: GPR119 is a G protein-coupled receptor (GPCR) that is highly expressed in
      pancreatic beta-cells and intestinal L-cells and facilitates glucose-stimulated
      insulin secretion (GSIS). GPR119 may represent a novel target for the treatment
      of metabolic disorders. Here, we sought to identify novel small-molecule GPR119
      agonists. METHODS: A cell-based high-throughput screening assay was established
      using HEK293 cells stably expressing GPR119 and pCRE-luc reporter plasmid
      (HEK293/GPR119/pCRE-luc). A compound library composed of 1440 compounds was
      screened. Mouse beta-cell line MIN-6 and isolated mouse islets were used to
      evaluate the effects of candidate compounds on GSIS in vitro. RESULTS: Three
      compounds with novel structures (ZSY-04, -06, and -13) were found to activate
      GPR119-mediated signaling and to induce GPR119 desensitization. The EC50 values
      of ZSY-04, -06, and -13 in stimulating intracellular cAMP accumulation in
      HEK293/GPR119 cells were 2.758, 3.046, and 0.778 MUmol/L, respectively.
      Furthermore, all three compounds displayed high selectivity for GPR119, and did
      not activate other 9 GPCRs tested. Moreover, all three compounds significantly
      increased GSIS in both MIN-6 mouse beta-cells and isolated mouse islets at
      concentration of 10 MUmol/L. CONCLUSION: Three novel small-molecule GPR119
      agonists (ZSY-04, -06, and -13) with high receptor selectivity and capacity to
      induce GSIS in vitro were discovered. These compounds are potential candidates to
      be structurally optimized into drugs for the treatment of type 2 diabetes.

PMID- 24681898
TI  - Psychopharmacological treatment of ADHD in adults aged 50+: an empirical study.
AB  - OBJECTIVE: To study pharmacotherapy in adults aged 50+ with ADHD. METHOD: A
      survey was administered to adults with ADHD (>= 50 years old). Participants on
      medication for ADHD were compared with those not on medications. RESULTS: Mean
      age of participants was 55.8 years, and mean age when diagnosed with ADHD was
      50.3 years. Ninety-five participants (63.8%) reported current
      psychopharmacological treatment for ADHD, 36 (24.2%) had stopped
      psychopharmacological treatment, and 18 (12.0%) were psychopharmacological
      treatment naive for ADHD. Those currently being treated psychopharmacologically
      for ADHD reported significantly improved attention relative to the two
      nonmedicated groups (p < .01). Among examined sample characteristics (including
      current psychopharmacological treatment for ADHD), employment was associated with
      a better outcome (odds ratio = 3.3, p = .006). CONCLUSION: The majority of adults
      aged 50+ with ADHD reported regular pharmacotherapy for ADHD. Participants
      currently receiving psychopharmacological treatment for ADHD reported better
      attention than those not receiving pharmacotherapy. Employment was associated
      with more favorable outcomes.

PMID- 24681894
TI  - Glutamate transporters in brain ischemia: to modulate or not?
AB  - In this review, we briefly describe glutamate (Glu) metabolism and its specific
      transports and receptors in the central nervous system (CNS). Thereafter, we
      focus on excitatory amino acid transporters, cystine/glutamate antiporters
      (system xc-) and vesicular glutamate transporters, specifically addressing their
      location and roles in CNS and the molecular mechanisms underlying the regulation
      of Glu transporters. We provide evidence from in vitro or in vivo studies
      concerning alterations in Glu transporter expression in response to hypoxia or
      ischemia, including limited human data that supports the role of Glu transporters
      in stroke patients. Moreover, the potential to induce brain tolerance to ischemia
      through modulation of the expression and/or activities of Glu transporters is
      also discussed. Finally we present strategies involving the application of
      ischemic preconditioning and pharmacological agents, eg beta-lactam antibiotics,
      amitriptyline, riluzole and N-acetylcysteine, which result in the significant
      protection of nervous tissues against ischemia. 

PMID- 24681899
TI  - Emotion Dysregulation Is Associated With Social Impairment Among Young
      Adolescents With ADHD.
AB  - OBJECTIVE: The purpose of this study was to evaluate aspects of emotion
      dysregulation (ED) that characterize young adolescents with ADHD, examine the
      effects of subtype and comorbidity, and determine the extent to which ED is
      related to aggression and rule-breaking and social impairment. METHOD: We
      examined which aspects of ED are most relevant to ADHD in 180 young adolescents
      (75% boys), as well as whether ED differs across ADHD subtypes or comorbid
      oppositional defiant disorder (ODD) status. We also examined the association
      between ED and aggression, rule-breaking, and social impairment. RESULTS: Young
      adolescent females and males with ADHD exhibited various manifestations of ED,
      including behavioral dyscontrol in the presence of strong emotions and
      inflexibility/slow return to emotional baseline. ED did not differ as a function
      of ADHD subtype or comorbid ODD. Three aspects of ED, namely, low threshold for
      emotional excitability/impatience, behavioral dyscontrol in the face of strong
      emotions, and inflexibility/slow return to baseline, predicted three of six
      measured indices of parent- and self-reported social impairment, above and beyond
      comorbid ODD. CONCLUSIONS: ED is associated with ADHD among young adolescents,
      does not differ based on ADHD subtype or ODD status, and is associated with
      social impairment.

PMID- 24681900
TI  - The joint effect of bilingualism and ADHD on executive functions.
AB  - OBJECTIVE: The current study investigated the combined effect of ADHD, previously
      associated with executive function (EF) deficits, and of bilingualism, previously
      associated with EF enhancement, on EF. METHOD: Eighty University students, Hebrew
      monolinguals and Russian Hebrew bilinguals, with and without ADHD participated.
      Inhibition tasks were a Numeric Stroop task and a Simon arrows task. Shifting
      tasks were the Trail Making Test (TMT) and a task-switching paradigm. RESULTS:
      Participants with ADHD performed worse than controls, but we did not find a
      bilingual advantage in EF. The negative impact of ADHD was more pronounced for
      bilinguals than for monolinguals, but only in interference suppression tasks.
      Bilingual participants with ADHD had the lowest performance. CONCLUSION:
      Bilingualism might prove to be an added burden for adults with ADHD, leading to
      reduced EF abilities. Alternatively, the current findings might be ascribed to
      over- or under-diagnosis of ADHD due to cultural differences between groups.
      These issues should be pursued in future research.

PMID- 24681901
TI  - Enhanced stability of a naringenin/2,6-dimethyl beta-cyclodextrin inclusion
      complex: molecular dynamics and free energy calculations based on MM- and QM
      PBSA/GBSA.
AB  - The structure, dynamic behavior and binding affinity of the inclusion complexes
      between naringenin and the two cyclodextrins (CDs), beta-CD and its 2,6-dimethyl
      derivative (DM-beta-CD), were theoretically studied by multiple molecular
      dynamics simulations and free energy calculations. Naringenin most likely prefers
      to bind with CDs through the phenyl ring. Although a lower hydrogen bond
      formation of naringenin with the 3-hydroxyl group of DM-beta-CD (relative to beta
      CD) was observed, the higher cavity could encapsulate almost the whole naringenin
      molecule. In contrast for the naringenin/beta-CD complex, the phenyl ring
      feasibly passed through the primary rim resulting in the chromone ring binding
      inside instead. MM-PBSA/GBSA and QM-PBSA/GBSA binding free energies strongly
      suggested a greater stability of the naringenin/DM-beta-CD inclusion complex. Van
      der Waals force played an important role as the key guest-host interaction for
      the complexation between naringenin and each cyclodextrin.

PMID- 24681902
TI  - Delta12-Fatty acid desaturase from Candida parapsilosis is a multifunctional
      desaturase producing a range of polyunsaturated and hydroxylated fatty acids.
AB  - Numerous Delta12-, Delta15- and multifunctional membrane fatty acid desaturases
      (FADs) have been identified in fungi, revealing great variability in the
      enzymatic specificities of FADs involved in biosynthesis of polyunsaturated fatty
      acids (PUFAs). Here, we report gene isolation and characterization of novel
      Delta12/Delta15- and Delta15-FADs named CpFad2 and CpFad3, respectively, from the
      opportunistic pathogenic yeast Candida parapsilosis. Overexpression of CpFad3 in
      Saccharomyces cerevisiae strains supplemented with linoleic acid (Delta9,Delta12
      18:2) and hexadecadienoic acid (Delta9,Delta12-16:2) leads to accumulation of
      Delta15-PUFAs, i.e., alpha-linolenic acid (Delta9,Delta12,Delta15-18:3) and
      hexadecatrienoic acid with an unusual terminal double bond
      (Delta9,Delta12,Delta15-16:3). CpFad2 produces a range of Delta12- and Delta15
      PUFAs. The major products of CpFad2 are linoleic and hexadecadienoic acid
      (Delta9,Delta12-16:2), accompanied by alpha-linolenic acid and hexadecatrienoic
      acid (Delta9,Delta12,Delta15-16:3). Using GC/MS analysis of trimethylsilyl
      derivatives, we identified ricinoleic acid (12-hydroxy-9-octadecenoic acid) as an
      additional product of CpFad2. These results demonstrate that CpFAD2 is a
      multifunctional FAD and indicate that detailed analysis of fatty acid derivatives
      might uncover a range of enzymatic selectivities in other Delta12-FADs from
      budding yeasts (Ascomycota: Saccharomycotina). 

PMID- 24681903
TI  - Census 2: isobaric labeling data analysis.
AB  - MOTIVATION: We introduce Census 2, an update of a mass spectrometry data analysis
      tool for peptide/protein quantification. New features for analysis of isobaric
      labeling, such as Tandem Mass Tag (TMT) or Isobaric Tags for Relative and
      Absolute Quantification (iTRAQ), have been added in this version, including a
      reporter ion impurity correction, a reporter ion intensity threshold filter and
      an option for weighted normalization to correct mixing errors. TMT/iTRAQ analysis
      can be performed on experiments using HCD (High Energy Collision Dissociation)
      only, CID (Collision Induced Dissociation)/HCD (High Energy Collision
      Dissociation) dual scans or HCD triple-stage mass spectrometry data. To improve
      measurement accuracy, we implemented weighted normalization, multiple tandem
      spectral approach, impurity correction and dynamic intensity threshold features.
      AVAILABILITY AND IMPLEMENTATION: Census 2 supports multiple input file formats
      including MS1/MS2, DTASelect, mzXML and pepXML. It requires JAVA version 6 or
      later to run. Free download of Census 2 for academic users is available at
      http://fields.scripps.edu/census/index.php. CONTACT: jyates@scripps.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24681904
TI  - CorMut: an R/Bioconductor package for computing correlated mutations based on
      selection pressure.
AB  - Correlated mutations constitute a fundamental idea in evolutionary biology, and
      understanding correlated mutations will, in turn, facilitate an understanding of
      the genetic mechanisms governing evolution. CorMut is an R package designed to
      compute correlated mutations in the unit of codon or amino acid mutation. Three
      classical methods were incorporated, and the computation results can be
      represented as correlation mutation networks. CorMut also enables the comparison
      of correlated mutations between two different evolutionary conditions.
      AVAILABILITY AND IMPLEMENTATION: CorMut is released under the GNU General Public
      License within bioconductor project, and freely available at
      http://bioconductor.org/packages/release/bioc/html/CorMut.html.

PMID- 24681905
TI  - Motifs tree: a new method for predicting post-translational modifications.
AB  - MOTIVATION: Post-translational modifications (PTMs) are important steps in the
      maturation of proteins. Several models exist to predict specific PTMs, from
      manually detected patterns to machine learning methods. On one hand, the manual
      detection of patterns does not provide the most efficient classifiers and
      requires an important workload, and on the other hand, models built by machine
      learning methods are hard to interpret and do not increase biological knowledge.
      Therefore, we developed a novel method based on patterns discovery and decision
      trees to predict PTMs. The proposed algorithm builds a decision tree, by coupling
      the C4.5 algorithm with genetic algorithms, producing high-performance white box
      classifiers. Our method was tested on the initiator methionine cleavage (IMC) and
      N(alpha)-terminal acetylation (N-Ac), two of the most common PTMs. RESULTS: The
      resulting classifiers perform well when compared with existing models. On a set
      of eukaryotic proteins, they display a cross-validated Matthews correlation
      coefficient of 0.83 (IMC) and 0.65 (N-Ac). When used to predict potential
      substrates of N-terminal acetyltransferaseB and N-terminal acetyltransferaseC,
      our classifiers display better performance than the state of the art. Moreover,
      we present an analysis of the model predicting IMC for Homo sapiens proteins and
      demonstrate that we are able to extract experimentally known facts without prior
      knowledge. Those results validate the fact that our method produces white box
      models. AVAILABILITY AND IMPLEMENTATION: Predictors for IMC and N-Ac and all
      datasets are freely available at http://terminus.unige.ch/.

PMID- 24681906
TI  - GAP: towards almost 100 percent prediction for beta-strand-mediated aggregating
      peptides with distinct morphologies.
AB  - MOTIVATION: Distinguishing between amyloid fibril-forming and amorphous beta
      aggregating aggregation-prone regions (APRs) in proteins and peptides is crucial
      for designing novel biomaterials and improved aggregation inhibitors for
      biotechnological and therapeutic purposes. RESULTS: Adjacent and alternate
      position residue pairs in hexapeptides show distinct preferences for occurrence
      in amyloid fibrils and amorphous beta-aggregates. These observations were
      converted into energy potentials that were, in turn, machine learned. The
      resulting tool, called Generalized Aggregation Proneness (GAP), could
      successfully distinguish between amyloid fibril-forming and amorphous beta
      aggregating hexapeptides with almost 100 percent accuracies in validation tests
      performed using non-redundant datasets. CONCLUSION: Accuracies of the predictions
      made by GAP are significantly improved compared with other methods capable of
      predicting either general beta-aggregation or amyloid fibril-forming APRs. This
      work demonstrates that amino acid side chains play important roles in determining
      the morphological fate of beta-mediated aggregates formed by short peptides.
      AVAILABILITY AND IMPLEMENTATION: http://www.iitm.ac.in/bioinfo/GAP/.

PMID- 24681907
TI  - VariantAnnotation: a Bioconductor package for exploration and annotation of
      genetic variants.
AB  - VariantAnnotation is an R / Bioconductor package for the exploration and
      annotation of genetic variants. Capabilities exist for reading, writing and
      filtering variant call format (VCF) files. VariantAnnotation allows ready access
      to additional R / Bioconductor facilities for advanced statistical analysis, data
      transformation, visualization and integration with diverse genomic resources.
      AVAILABILITY AND IMPLEMENTATION: This package is implemented in R and available
      for download at the Bioconductor Web site
      (http://bioconductor.org/packages/2.13/bioc/html/VariantAnnotation.html). The
      package contains extensive help pages for individual functions and a 'vignette'
      outlining typical work flows; it is made available under the open source
      'Artistic-2.0' license. Version 1.9.38 was used in this article.

PMID- 24681908
TI  - molBLOCKS: decomposing small molecule sets and uncovering enriched fragments.
AB  - The chemical structures of biomolecules, whether naturally occurring or
      synthetic, are composed of functionally important building blocks. Given a set of
      small molecules-for example, those known to bind a particular protein
      computationally decomposing them into chemically meaningful fragments can help
      elucidate their functional properties, and may be useful for designing novel
      compounds with similar properties. Here we introduce molBLOCKS, a suite of
      programs for breaking down sets of small molecules into fragments according to a
      predefined set of chemical rules, clustering the resulting fragments, and
      uncovering statistically enriched fragments. Among other applications, our
      software should be a great aid in large-scale chemical analysis of ligands
      binding specific targets of interest. AVAILABILITY AND IMPLEMENTATION: molBLOCKS
      is available as GPL C++ source code at http://compbio.cs.princeton.edu/molblocks.

PMID- 24681909
TI  - flowFit: a Bioconductor package to estimate proliferation in cell-tracking dye
      studies.
AB  - SUMMARY: Herein we introduce flowFit, a Bioconductor package designed to perform
      quantitative analysis of cell proliferation in tracking dye-based experiments.
      The software, distributed as an R Bioconductor library, is based on a
      mathematical model that takes into account the height of each peak, the size and
      position of the parental population (labeled but not proliferating) and the
      estimated distance between the brightness of a cell and the brightness of its
      daughter (in which the dye is assumed to undergo a 2-fold dilution). Although the
      algorithm does not make any inference on cell types, rates of cell divisions or
      rates of cell death, it deconvolutes the actual collected data into a set of
      peaks, whereby each peak corresponds to a subpopulation of cells that have
      divided N times. We validated flowFit by retrospective analysis of published
      proliferation-tracking experiments and demonstrated that the algorithm predicts
      the same percentage of cells/generation either in samples with discernible peaks
      (in which the peaks are visible in the collected raw data) or in samples with non
      discernible peaks (in which the peaks are fused together). To the best of our
      knowledge, flowFit represents the first open-source algorithm in its category and
      might be applied to numerous areas of cell biology in which quantitative
      deconvolution of tracking dye-based experiments is desired, including stem cell
      research. AVAILABILITY AND IMPLEMENTATION:
      http://www.bioconductor.org/packages/devel/bioc/html/flowFit.html (Bioconductor
      software page).
      http://www.bioconductor.org/packages/2.13/bioc/vignettes/flowFit/inst/doc/HowTo
      flowFit.pdf (package vignette). http://rpubs.com/tucano/flowFit (online
      tutorial).

PMID- 24681910
TI  - Second-generation antipsychotic drug use in hospital inpatients with dementia:
      the impact of a safety warning on rates of prescribing.
AB  - BACKGROUND: Behavioural and psychological symptoms of dementia are distressing
      for patients and are frequently treated with second-generation antipsychotics.
      Concerns about the drugs' safety resulted in a Medicines and Healthcare Products
      Regulatory Agency (MHRA) warning against their use in March 2009. METHODS: Second
      generation antipsychotic drug use was determined amongst patients with dementia
      admitted to the University Hospitals Birmingham National Health Service
      Foundation Trust, between July 2005 and December 2011. An interrupted time series
      analysis was carried out to investigate changes in rates of prescribing following
      the safety warning. Risperidone was analysed separately, in accordance with its
      limited licence for use in older adults with dementia, granted in October 2008.
      RESULTS: Before the safety warning, second-generation antipsychotic use was
      increasing in patients with dementia. After the MHRA warning, their use fell by
      1.9% per month compared with that before. Use of risperidone continued to rise
      over the same period, often against the terms of its licence. CONCLUSIONS: Drug
      safety warnings may influence prescribing practice, although continued use of
      antipsychotics in dementia could reflect a lack of alternative treatment options.

PMID- 24681911
TI  - Association of metabolically abnormal but normal weight (MANW) and metabolically
      healthy but obese (MHO) individuals with arterial stiffness and carotid
      atherosclerosis.
AB  - OBJECTIVE: Despite recent interest in differential impact of body size phenotypes
      on cardiovascular outcomes and mortality, studies evaluating the association
      between body size phenotypes and indicators of atherosclerosis are limited. This
      study investigated the relationship of metabolically abnormal but normal weight
      (MANW) and metabolically healthy but obese (MHO) individuals with arterial
      stiffness and carotid atherosclerosis in Korean adults without cardiovascular
      disease. METHODS: A total of 1012 participants (575 men and 437 women, mean age
      50.8 years), who underwent a health examination between April 2012 and May 2013
      were prospectively enrolled based on inclusion and exclusion criteria. Study
      subjects were classified according to body mass index (BMI) and the
      presence/absence of metabolic syndrome. RESULTS: The prevalence of metabolically
      healthy normal weight (MHNW), MANW, MHO, and metabolically abnormal obese (MAO)
      were 54.84%, 6.42%, 22.83%, and 15.91%, respectively. Individuals with MANW had
      significantly higher brachial-ankle pulse wave velocity and maximal carotid
      intima-media thickness values than those with MHO, after adjusting for age and
      gender (P = 0.026 and P = 0.018, respectively). The odds ratio (OR) of arterial
      stiffness and carotid atherosclerosis in the MANW group were significantly higher
      than in the MHNW group in unadjusted models. Furthermore, multivariable models
      showed that increased OR of carotid atherosclerosis in the MANW group persisted
      even after adjusting for confounding factors (OR = 2.98, 95% CI = [1.54, 5.73], P
      = 0.011). CONCLUSIONS: Compared to MHNW or MHO subjects, Korean men and women
      with the MANW phenotype exhibited increased arterial stiffness and carotid
      atherosclerosis. CLINICAL TRIALS NO: NCT01594710.

PMID- 24681912
TI  - High-potency statins increase the risk of acute kidney injury: evidence from a
      large population-based study.
AB  - OBJECTIVE: To assess the association between acute kidney injury and exposure to
      either high-potency statins or low-potency statins. DESIGN: A population-based,
      nested case-control study was performed on a cohort of 316,449 patients from
      Lombardy (Italy) newly treated with statins between 2007 and 2010 aged 40 years
      or older. 458 patients experienced acute kidney injury within six months after
      initial statin prescription. Up to four controls were randomly selected for each
      case. Logistic regression was used to model the outcome risk associated with high
      potency contrasted with low-potency statins dispensed at starting therapy, and
      during follow-up. RESULTS: Patients at whom high-potency statins were initially
      dispensed were more likely to be hospitalized for acute kidney injury within six
      months after starting treatment than those on low-potency statins (adjusted OR
      1.54, 95% confidence interval 1.25-1.91). Patients receiving high-potency statins
      within three weeks before the outcome onset had a significant increased risk
      respect to those who did not receive statins during the same time-window
      (adjusted OR 1.45, 95% confidence interval 1.04-2.03). When follow-up was
      extended from 6 months to 12 months the difference was not significant anymore
      (adjusted OR 1.17, 95% confidence interval 0.89-1.54). CONCLUSIONS: Use of high
      potency statins is associated with an increased risk of acute kidney injury
      compared with low-potency statins in the first 6 months after starting therapy.

PMID- 24681913
TI  - Normative and mean carotid intima-media thickness values according to metabolic
      syndrome in Koreans: the Namwon study.
AB  - OBJECTIVES: We determined the gender- and age-specific normative values of
      carotid intima-media thickness (IMT) in a healthy Korean population. We also
      present the mean age-specific carotid IMT values according to the presence of
      metabolic syndrome (MetS) and the number of MetS components. METHODS: A total of
      9374 subjects from the Namwon Study aged 45-74 years were included in the
      analysis. Subjects without hypertension, diabetes, dyslipidemia, obesity, and
      current smoking were classified as the healthy reference population (n = 2595).
      MetS was identified by the presence of three or more of the following five
      components: abdominal obesity, high triglycerides, low high-density lipoprotein
      cholesterol, high blood pressure, and high fasting blood glucose. Common carotid
      artery IMT (CCA-IMT) and carotid bulb IMT values were determined in a region free
      of plaque by B-mode carotid ultrasonography. RESULTS: The mean normative CCA-IMT
      values of 45-49, 50-54, 55-59, 60-64, 65-69, and 70-74 year old males were 0.614,
      0.671, 0.711, 0.759, 0.783, and 0.787 mm and 0.613, 0.653, 0.689, 0.718, 0.753,
      and 0.778 mm for females, respectively. An increase in CCA-IMT of 0.007 mm/year
      was estimated in both genders. The mean CCA-IMT values of subjects with 0, 1, 2,
      3, 4, and 5 MetS components were 0.744, 0.753, 0.765, 0.766, 0.771, and 0.798 mm
      for males and 0.688, 0.705, 0.724, 0.734, 0.757, and 0.762 mm for females,
      respectively. CONCLUSION: The gender-specific normative carotid IMT values were
      determined in a large healthy Korean population. An increasing trend in the CCA
      IMT values was observed with an increasing number of MetS components in both
      genders.

PMID- 24681914
TI  - Cancer pain assessment.
AB  - PURPOSE OF REVIEW: Adequate cancer pain assessment using valid and reliable tools
      is essential for proper cancer pain management. Because cancer pain can be a
      complex construct, assessment of its many domains should be conducted using
      multidimensional tools. Furthermore, there is a need to develop a standard,
      consensus classification system for prognosis of cancer pain. RECENT FINDINGS:
      Unidimensional tools for assessing cancer pain are useful for measuring cancer
      pain intensity. Other domains and symptoms of the cancer pain experience are
      assessed using a variety of multidimensional tools. There is a lack of agreement
      on a standard assessment tool or a standard classification system for cancer
      pain, although research continues to be undertaken to develop such resources for
      clinical and research purposes. SUMMARY: Many pain and symptom assessment tools
      exist for use in the cancer patient, including the Brief Pain Inventory, the
      McGill Pain Questionnaire, the MD Anderson Symptom Inventory, and the Edmonton
      Symptom Assessment System, among others. Recent literature reveals the move
      toward translating these and other tools to electronic applications. Further
      study is also underway to create a standard, prognostic classification system for
      cancer pain.

PMID- 24681915
TI  - Developing trends in aptamer-based biosensor devices and their applications.
AB  - Aptamers are, in general, easier to produce, easier to store and are able to bind
      to a wider variety of targets than antibodies. For these reasons, aptamers are
      gaining increasing popularity in environmental monitoring as well as disease
      detection and disease management applications. This review article examines the
      research and design of RNA and DNA aptamer based biosensor systems and
      applications as well as their potential for integration in effective biosensor
      devices. As single stranded DNA or RNA molecules that can bind to specific
      targets, aptamers are well suited for biomolecular recognition and sensing
      applications. Beyond being able to be designed for a near endless number of
      specific targets, aptamers can also be made which change their conformation in a
      predictable and consistent way upon binding. This can lead to many unique and
      effective detection methods using a variety of optical and electrochemical means.

PMID- 24681916
TI  - A surface-stress-based microcantilever aptasensor.
AB  - Biosensors based on microcantilevers convert biological recognition events into
      measurable mechanical displacements. They offer advantages such as small size,
      low sample volume, label-free detection, ease of integration, high-throughput
      analysis, and low development cost. The design and development of a
      microcantilever-based aptasensor employing SU-8 polymer as the fabrication
      material is presented in this paper. Aptamers are employed as bioreceptor
      elements because they exhibit superior specificity compared to antibodies due to
      their small size and physicochemical stability. To immobilise thrombin DNA
      aptamer on the bare SU-8 surface of the aptasensor, a combined plasma mode
      treatment method is implemented which modifies the surface of the aptasensor.
      Label-free detection of thrombin molecules using the fabricated aptasensor is
      successfully demonstrated. The measured deflection is one order of magnitude
      higher than that of a silicon nitride microcantilever biosensor. The developed
      aptasensor also demonstrates high specificity. 

PMID- 24681917
TI  - Thermally controlled electrochemical CMOS microsystem for protein array
      biosensors.
AB  - Because many proteins useful in biosensors exhibit temperature dependent
      activity, this paper explores the opportunity to integrate thermal control within
      a protein array biosensor microsystem. A CMOS microhotplate array tailored to
      protein interfaces was developed for thermoregulation in a liquid sample
      environment. The microhotplates were shown to provide suitable thermal control
      for biosensor temperature ranges without the process complexity of most
      previously reported microhotplates. When combined with a CMOS analog thermal
      controller, the on-chip array was shown to set and hold temperatures for each
      protein site within +/-1( degrees ) C, and array elements were found to be almost
      completely thermally isolated from each other at distances beyond 0.4 mm. The
      compact size and low power of this controller enable it to be combined with the
      thermal control structures and instantiated for every element in a sensor array
      to increase biosensor interrogation throughput. 

PMID- 24681918
TI  - Stochastic multiple-valued gene networks.
AB  - Among various approaches to modeling gene regulatory networks (GRNs), Boolean
      networks (BNs) and its probabilistic extension, probabilistic Boolean networks
      (PBNs), have been studied to gain insights into the dynamics of GRNs. To further
      exploit the simplicity of logical models, a multiple-valued network employs gene
      states that are not limited to binary values, thus providing a finer granularity
      in the modeling of GRNs. In this paper, stochastic multiple-valued networks
      (SMNs) are proposed for modeling the effects of noise and gene perturbation in a
      GRN. An SMN enables an accurate and efficient simulation of a probabilistic
      multiple-valued network (as an extension of a PBN). In a k-level SMN of n genes,
      it requires a complexity of O(nLk(n)) to compute the state transition matrix,
      where L is a factor related to the minimum sequence length in the SMN for
      achieving a desired accuracy. The use of randomly permuted stochastic sequences
      further increases computational efficiency and allows for a tunable tradeoff
      between accuracy and efficiency. The analysis of a p53-Mdm2 network and a WNT5A
      network shows that the proposed SMN approach is efficient in evaluating the
      network dynamics and steady state distribution of gene networks under random gene
      perturbation. 

PMID- 24681919
TI  - The RNA polymerase flow model of gene transcription.
AB  - Gene expression is a fundamental cellular process by which proteins are
      synthesized based on the information coded in the genes. The two major steps of
      this process are the transcription of the DNA segment corresponding to a gene to
      mRNA molecules and the translation of the mRNA molecules to proteins by the
      ribosome. Thus, understanding, modeling and engineering the different stages of
      this process have both important biotechnological applications and contributions
      to basic life science. In previous studies we have introduced the Homogenous
      Ribosome Flow Model (HRFM) and demonstrated its advantages in analyses of the
      translation process. In this study we introduce the RNA Polymerase Flow Model
      (RPFM), a non trivial extension of the HRFM, which also includes a backward flow
      and can be used for modeling transcription and maybe other similar processes. We
      compare the HRFM and the RPFM in the three regimes of the transcription process:
      rate limiting initiation, rate limiting elongation and rate limiting termination
      via a simulative and analytical analysis. In addition, based on experimental
      data, we show that RPFM is a better choice for modeling transcription process. 

PMID- 24681920
TI  - A Newtonian framework for community detection in undirected biological networks.
AB  - Community detection is a key problem of interest in network analysis, with
      applications in a variety of domains such as biological networks, social network
      modeling, and communication pattern analysis. In this paper, we present a novel
      framework for community detection that is motivated by a physical system analogy.
      We model a network as a system of point masses, and drive the process of
      community detection, by leveraging the Newtonian interactions between the point
      masses. Our framework is designed to be generic and extensible relative to the
      model parameters that are most suited for the problem domain. We illustrate the
      applicability of our approach by applying the Newtonian Community Detection
      algorithm on protein-protein interaction networks of E. coli , C. elegans, and S.
      cerevisiae. We obtain results that are comparable in quality to those obtained
      from the Newman-Girvan algorithm, a widely employed divisive algorithm for
      community detection. We also present a detailed analysis of the structural
      properties of the communities produced by our proposed algorithm, together with a
      biological interpretation using E. coli protein network as a case study. A
      functional enrichment heat map is constructed with the Gene Ontology functional
      mapping, in addition to a pathway analysis for each community. The analysis
      illustrates that the proposed algorithm elicits communities that are not only
      meaningful from a topological standpoint, but also possess biological relevance.
      We believe that our algorithm has the potential to serve as a key computational
      tool for driving therapeutic applications involving targeted drug development for
      personalized care delivery. 

PMID- 24681922
TI  - Identification and evolution of structurally dominant nodes in protein-protein
      interaction networks.
AB  - It is well known that protein-protein interaction (PPI) networks are typical
      evolving complex networks. Identification of important nodes has been an emerging
      popular topic in complex networks. Many indexes have been proposed to measure the
      importance of nodes in complex networks, such as degree, closeness, betweenness,
      k-shell, clustering coefficient, semi-local centrality, eigenvector centrality.
      Based on multivariate statistical analysis, through integrating the above indexes
      and further considering the appearances of nodes in network motifs, this paper
      aims at developing a new measure to characterize the structurally dominant
      proteins (SDP) in PPI networks. Moreover, we will further investigate the
      evolution of the defined dominant nodes in temporal evolving real-world and
      artificial PPI networks. Our results indicate that the constructed artificial
      networks have some similar statistical properties as those of the real-world
      evolving networks. In this case, the artificial PPI networks can be used to
      further investigate the above evolution characteristics of the real-world
      evolving networks. Simulation results reveal that SDP in the yeast PPI networks
      are evolutionary conserved, however, the undominant nodes evolve rapidly.
      Furthermore, PPI networks are very robust against random mutations, while fragile
      yet with certain robustness to targeted mutations on SDP. Our investigations shed
      some light on the future applications of the evolving characteristics of bio
      molecular networks, such as reengineering of particular networks for
      technological, synthetic or pharmacological purposes. 

PMID- 24681921
TI  - Time-varying causal inference from phosphoproteomic measurements in macrophage
      cells.
AB  - Cellular signaling circuitry in eukaryotes can be studied by analyzing the
      regulation of protein phosphorylation and its impact on downstream mechanisms
      leading to a phenotype. A primary role of phosphorylation is to act as a switch
      to turn "on" or "off" a protein activity or a cellular pathway. Specifically,
      protein phosphorylation is a major leit motif for transducing molecular signals
      inside the cell. Errors in transferring cellular information can alter the normal
      function and may lead to diseases such as cancer; an accurate reconstruction of
      the "true" signaling network is essential for understanding the molecular
      machinery involved in normal and pathological function. In this study, we have
      developed a novel framework for time-dependent reconstruction of signaling
      networks involved in the activation of macrophage cells leading to an
      inflammatory response. Several signaling pathways have been identified in
      macrophage cells, but the time-varying causal relationship that can produce a
      dynamic directed graph of these molecules has not been explored in detail. Here,
      we use the notion of Granger causality, and apply a vector autoregressive model
      to phosphoprotein time-course data in RAW 264.7 macrophage cells. Through the
      reconstruction of the phosphoprotein network, we were able to estimate the
      directionality and the dynamics of information flow. Significant interactions
      were selected through statistical hypothesis testing ( t-test) of the
      coefficients of a linear model and were used to reconstruct the phosphoprotein
      signaling network. Our approach results in a three-stage phosphoprotein network
      that represents the evolution of the causal interactions in the intracellular
      signaling pathways. 

PMID- 24681923
TI  - An event-based neural network architecture with an asynchronous programmable
      synaptic memory.
AB  - We present a hybrid analog/digital very large scale integration (VLSI)
      implementation of a spiking neural network with programmable synaptic weights.
      The synaptic weight values are stored in an asynchronous Static Random Access
      Memory (SRAM) module, which is interfaced to a fast current-mode event-driven DAC
      for producing synaptic currents with the appropriate amplitude values. These
      currents are further integrated by current-mode integrator synapses to produce
      biophysically realistic temporal dynamics. The synapse output currents are then
      integrated by compact and efficient integrate and fire silicon neuron circuits
      with spike-frequency adaptation and adjustable refractory period and spike-reset
      voltage settings. The fabricated chip comprises a total of 32 * 32 SRAM cells, 4
      * 32 synapse circuits and 32 * 1 silicon neurons. It acts as a transceiver,
      receiving asynchronous events in input, performing neural computation with hybrid
      analog/digital circuits on the input spikes, and eventually producing digital
      asynchronous events in output. Input, output, and synaptic weight values are
      transmitted to/from the chip using a common communication protocol based on the
      Address Event Representation (AER). Using this representation it is possible to
      interface the device to a workstation or a micro-controller and explore the
      effect of different types of Spike-Timing Dependent Plasticity (STDP) learning
      algorithms for updating the synaptic weights values in the SRAM module. We
      present experimental results demonstrating the correct operation of all the
      circuits present on the chip. 

PMID- 24681924
TI  - Safety ensuring retinal prosthesis with precise charge balance and low power
      consumption.
AB  - Ensuring safe operation of stimulators is the most important issue in neural
      stimulation. Safety, in terms of stimulators' electrical performances, can be
      related mainly to two factors; the zero-net charge transfer to tissue and the
      heat generated by power dissipation at tissue. This paper presents a safety
      ensuring neuro-stimulator for retinal vision prostheses, featuring precise charge
      balancing capability and low power consumption, using a 0.35 MUm HV (high
      voltage) CMOS process. Also, the required matching accuracy of the biphasic
      current pulse for safe stimulation is mathematically derived. Accurate charge
      balance is achieved by employing a dynamic current mirror at the output of a
      stimulator. In experiments, using a simple electrode model (a resistor (R) and a
      capacitor (C) in parallel), the proposed stimulator ensures less than 30 nA DC
      current flowing into tissue over all stimulation current ranges (32 MUA-1 mA),
      without shorting. With shorting enabled, further reduction is achieved down to
      1.5 nA. Low power consumption was achieved by utilising small bias current,
      sharing of key biasing blocks, and utilising a short duty cycle for stimulation.
      Less than 30 MUW was consumed during stand-by mode, mostly by bias circuitry. 

PMID- 24681925
TI  - Multi-frequency electrical impedance tomography system with automatic self
      calibration for long-term monitoring.
AB  - Electrical Impedance Tomography (EIT) is a safe medical imaging technology,
      requiring no ionizing or heating radiation, as opposed to most other imaging
      modalities. This has led to a clinical interest in its use for long-term
      monitoring, possibly at the bedside, for ventilation monitoring, bleeding
      detection, gastric emptying and epilepsy foci diagnosis. These long-term
      applications demand auto-calibration and high stability over long time periods.
      To address this need we have developed a new multi-frequency EIT system called
      the KHU Mark2.5 with automatic self-calibration and cooperation with other
      devices via a timing signal for synchronization with other medical instruments.
      The impedance measurement module (IMM) for flexible configuration as a key
      component includes an independent constant current source, an independent
      differential voltmeter, and a current source calibrator, which allows automatic
      self-calibration of the current source within each IMM. We installed a resistor
      phantom inside the KHU Mark2.5 EIT system for intra-channel and inter-channel
      calibrations of all voltmeters in multiple IMMs. We show the deterioration of
      performance of an EIT system over time and the improvement due to automatic self
      calibration. The system is able to maintain SNR of 80 dB for frequencies up to
      250 kHz and below 0.5% reciprocity error over continuous operation for 24 hours.
      Automatic calibration at least every 3 days is shown to maintain SNR above 75 dB
      and reciprocity error below 0.7% over 7 days at 1 kHz. A clear degradation in
      performance results with increasing time between automatic calibrations allowing
      the tailoring of calibration to suit the performance requirements of each
      application. 

PMID- 24681926
TI  - Data compression in brain-machine/computer interfaces based on the Walsh-Hadamard
      transform.
AB  - This paper reports on the application of the Walsh-Hadamard transform (WHT) for
      data compression in brain-machine/brain-computer interfaces. Using the proposed
      technique, the amount of the neural data transmitted off the implant is
      compressed by a factor of at least 63 at the expense of as low as 4.66% RMS error
      between the signal reconstructed on the external host and the original neural
      signal on the implant side. Based on the proposed idea, a 128-channel WHT
      processor was designed in a 0.18- MUm CMOS process occupying 1.64 mm(2) of
      silicon area. The circuit consumes 81 MUW (0.63 MUW per channel) from a 1.8-V
      power supply at 250 kHz. A prototype of the proposed processor was implemented
      and successfully tested using prerecorded neural signals. 

PMID- 24681927
TI  - A 0.5 cm(3) four-channel 1.1 mW wireless biosignal interface with 20 m range.
AB  - This paper presents a self-contained, single-chip biosignal monitoring system
      with wireless programmability and telemetry interface suitable for mainstream
      healthcare applications. The system consists of low-noise front end amplifiers,
      ADC, MICS/ISM transmitter and infrared programming capability to configure the
      state of the chip. An on-chip packetizer ensures easy pairing with standard off
      the-shelf receivers. The chip is realized in the IBM 130 nm CMOS process with an
      area of 2*2 mm(2). The entire system consumes 1.07 mW from a 1.2 V supply. It
      weighs 0.6 g including a zinc-air battery. The system has been extensively tested
      in in vivo biological experiments and requires minimal human interaction or
      calibration. 

PMID- 24681929
TI  - Electrochemical redox responsive polymeric micelles formed from amphiphilic
      supramolecular brushes.
AB  - The end-decorated homopolymer poly(epsilon-caprolactone)-ferrocene threaded onto
      a beta-cyclodextrin-functionalized main-chain polymer can form a class of
      amphiphilic noncovalent graft copolymers based on the host-guest interactions of
      the terminal groups on the side chains. These new supramolecular polymer brushes
      can further self-assemble into micellar aggregates that exhibit reversible
      assembly and disassembly behavior under an electrochemical redox trigger, which
      opens up a new route to building dynamic block copolymer topologies. 

PMID- 24681930
TI  - [Picture in clinical hematology no. 71: Case of fungemia caused by Fusarium
      complicated with intractable acute myeloid leukemia].

PMID- 24681931
TI  - [Clinical aspects of primary myelofibrosis in Japan].

PMID- 24681932
TI  - [Future therapeutic strategy for multiple myeloma through the targeting of cell
      signaling pathways].

PMID- 24681933
TI  - [Determinants of sensitivity to proteasome inhibitors and strategies to overcome
      acquired resistance to bortezomib in multiple myeloma].

PMID- 24681934
TI  - [Recommendation for the optimal use of bendamustine in Japan].

PMID- 24681935
TI  - [Methotrexate-related lymphomatoid granulomatosis successfully treated with
      discontinuation of methotrexate and radiotherapy to brain].
AB  - A 70-year-old woman with rheumatoid arthritis treated with methotrexate (MTX)
      complained of right arm weakness. On CT and MRI, tumors were found in the right
      frontal lobe, bilateral lungs, and left renal parenchyma. She was diagnosed as
      having lymphomatoid granulomatosis (LYG) grade 2 on thoracoscopic biopsy of the
      left lung. We discontinued MTX and treated a mass lesion in the right frontal
      lobe with stereotactic radiotherapy. As a result, the tumors showed a gradual
      reduction in size, and the patient achieved complete remission. LYG is a rare
      lymphoproliferative disorder, and has various clinical characteristics. We
      describe herein a patient with LYG grade 2 with cerebral, pulmonary, and renal
      lesions, who has maintained a complete remission for six months, to date, after
      treatment.

PMID- 24681936
TI  - [Efficacy of chemotherapy combined with bortezomib for two cases of
      relapsed/refractory acute lymphoblastic leukemia].
AB  - Bortezomib (BZM), a proteasome inhibitor, was recently reported to be effective
      against acute lymphoblastic leukemia (ALL). We report two cases of
      relapsed/refractory ALL, who were treated with BZM (1.3 mg/m2/dose, 2 doses/week
      for 2 weeks) in combination with vincristine, doxorubicin, dexamethasone, and L
      asparaginase (L-ASP). The first patient was a 16-year-old girl who developed a
      bone marrow relapse 8 months after the initial diagnosis during consolidation
      chemotherapy. She received BZM-combined chemotherapy without L-ASP considering
      her previous history of an allergic reaction to L-ASP. The BZM-combined regimen
      was discontinued due to interstitial pneumonia development on day 13, and the
      interstitial pneumonia was successfully treated with steroid pulse therapy.
      Although her elevated serum LDH transiently normalized on day 16, blasts in
      peripheral blood did not disappear, and she died of leukemia without achieving
      remission. The second patient was a 17-year-old girl who developed a third bone
      marrow relapse after cord blood transplantation. She was given the same BZM
      combined regimen. Although the BZM-combined regimen was discontinued due to acute
      pancreatitis development on day 12, complete remission without platelet recovery
      was confirmed on day 62. Our experience suggests not only the effectiveness of
      BZM-combined chemotherapy but also the importance of controlling its toxicities
      when administered as a salvage therapy for advanced ALL patients.

PMID- 24681937
TI  - [Primary systemic AL amyloidosis with remarkable calcification in the spleen].
AB  - We report a 50-year-old female patient with diffuse and rapidly progressing
      splenic calcification. She had developed nephrotic syndrome and been diagnosed
      with renal amyloid light-chain amyloidosis in 2010. Although she had been given
      melphalan and dexamethasone therapy and high-dose melphalan followed by
      autologous blood stem-cell transplantation, her renal function worsened and
      hemodialysis was started in May 2011. Since November 2011, splenic calcification,
      probably associated with amyloidosis, had progressed, and diffuse calcification
      was observed throughout the splenic area in September 2012. During the same
      period, the patient was hospitalized for thrombocytopenia. Although splenic
      dysfunction due to calcification was suspected to be the cause of
      thrombocytopenia, the association between the two could not be established. The
      platelet count rose with an improvement in hepatic congestion due to reinforced
      fluid removal during dialysis.

PMID- 24681938
TI  - [Mucosa-associated lymphoid tissue lymphoma of the larynx].
AB  - A 63-year-old female suffering from hepatitis C virus infection and manic
      depression was admitted with a 4-month history of hoarseness. Endoscopic
      examination revealed the presence of a neoplasm with a smooth surface in the left
      supraglottic region extending to the left false vocal cord. Based on the
      histological findings, together with the results of systemic evaluation, the
      patient was diagnosed as having a mucosa-associated lymphoid tissue (MALT)
      lymphoma in clinical stage IE, according to the Ann Arbor classification. After
      one month of follow-up, the patient presented with involvement of multiple
      subcutaneous regions in the left neck area, etc. Biopsies revealed the same type
      of lymphoma as that in the supraglottis. The disease was considered to have
      progressed to clinical stage IV. Six courses of R-CVP (rituximab,
      cyclophosphamide, vincristine and prednisolone) treatment resulted in complete
      remission of all lesions. Primary MALT lymphoma in the larynx is extremely rare.
      Since the first description by Diebold et al in 1990, only 43 cases have been
      reported. Among these reported cases, only 7 (16%) with progressive stages were
      described. The R-CVP regimen appears to be effective for the treatment of
      progressive primary MALT lymphoma of the larynx. Furthermore, hepatitis C virus
      infection is thought to be closely associated with the aggressive malignant
      process and subcutaneous dissemination.

PMID- 24681939
TI  - [Copper deficiency anemia morphologically mimicking myelodysplastic syndrome].
AB  - A 64-year-old man underwent kidney transplantation for progressive chronic renal
      failure which had developed 8 years after allogeneic bone marrow transplantation
      for acute myeloid leukemia. Because of post-operative complications, he had been
      placed on intravenous hyperalimentation. Three months after the transplantation,
      anemia rapidly progressed (hemoglobin, 7.9 g/dl). The proportion of reticulocytes
      was 0.2%, but white blood cell and platelet counts remained within normal ranges.
      Serum iron, vitamin B12, and folate levels were normal. Bone marrow examination
      showed the presence of ringed sideroblasts and cytoplasmic vacuoles in a fraction
      of erythroid cells. Megakaryocytes were adequate in number with normal
      morphology. Although the findings were consistent with refractory anemia with
      ringed sideroblasts according to the WHO classification, cytoplasmic vacuolations
      were also observed in myeloid cells, suggesting copper deficiency. Indeed, serum
      copper and ceruloplasmin levels were found to be low (33 MUg/dl and 11 mg/dl,
      respectively), and oral copper supplementation at a daily dose of 1 mg was
      initiated. There was a prompt increase in reticulocytes, and the hemoglobin level
      was normalized within one month, in response to this regimen. In progressive
      anemia cases with ringed sideroblasts in the bone marrow, copper deficiency
      should be considered in the differential diagnosis.

PMID- 24681940
TI  - [Efficacy of rituximab for TAFRO syndrome, a variant type of multicentric
      Castleman's disease].
AB  - A 48-year-old woman was hospitalized because of severe thrombocytopenia, leg
      edema, and fever. Intravenous immunoglobulin therapy was administered, but no
      efficacy was obtained. Her bone marrow was dry-tap, and fibrosis was found in the
      biopsy specimens. A positron emission tomographic study showed FDG-avid
      lymphadenopathy and hepatomegaly. Biopsy specimens of axillary lymph nodes showed
      Castleman's disease-like findings. Since she then developed severe proteinuria
      and massive pleural effusion, steroid therapy was started, providing temporary
      relief of symptoms other than the thrombocytopenia. However, rapid worsening of
      her general condition prompted us to attempt rituximab as salvage therapy. The
      pleural effusion, edema, and proteinuria disappeared soon after starting
      rituximab administration. Platelet counts also normalized and fibrosis of the
      bone marrow showed amelioration. Recently, a variant of multicentric Castleman's
      disease, termed the TAFRO syndrome, has been proposed, and our patient's features
      fit the diagnosis of this syndrome. Rituximab might be considered as a
      therapeutic option in such cases.

PMID- 24681941
TI  - [Cytomegalovirus mononucleosis complicated with peripheral facial palsy].
AB  - A 36-year-old woman was admitted to our hospital for further examination of an
      acute febrile illness with liver dysfunction. A peripheral blood smear displayed
      atypical lymphocytes. Cytomegalovirus (CMV) mononucleosis was diagnosed based on
      the detection of CMV-specific IgM and conventional CMV pp65 antigen. The physical
      examination on admission revealed signs of lower motor neuron right facial palsy.
      There were no significant cerebrospinal fluid findings, nor were there other
      neurological abnormalities. After receiving a short-course of oral
      corticosteroids, the patient gradually recovered from the facial paralysis. A one
      month follow-up examination indicated that she had fully recovered
      neurologically, showing disappearance of CMV-DNA and a significant increase in
      the anti-CMV IgG titer. To our knowledge, there has been only one previous report
      describing CMV as the cause of an isolated facial palsy combined with CMV
      mononucleosis.

PMID- 24681942
TI  - [Polycythemia vera developed after a major molecular response to imatinib
      mesylate treatment in a patient with chronic myelogenous leukemia].
AB  - A 68-year-old man complained of dizziness and was referred to our hospital by his
      primary physician for evaluation of an elevated leukocyte count. In April 2002,
      soon after the chronic phase of chronic myeloid leukemia had been diagnosed, he
      was treated with imatinib. In March 2010, imatinib treatment was completed and
      the BCR/ABL fusion gene had become undetectable by real time quantitative PCR.
      Subsequently, leukocyte counts and the hematocrit gradually rose. In August 2012,
      a bone marrow aspirate showed hypercellular marrow with marked erythroid
      hyperplasia and the presence of the JAK2 gene V617F mutation. He was diagnosed
      with polycythemia vera. Phlebotomy and chemotherapy were started in addition to
      imatinib administration. Shortly thereafter complete blood counts returned to
      normal levels.

PMID- 24681945
TI  - Ecological validity of performance validity testing.
AB  - Performance validity tests (PVTs) have been shown to relate to neuropsychological
      performance, but no studies have looked at the ecological validity of these
      measures. Data from 131 veterans with a history of mild traumatic brain injury
      from a multicenter Veterans Administration consortium were examined to determine
      the relation between scores on a self-report version of the Mayo-Portland
      Adaptability Inventory Participation Index, a measure of community participation,
      and the Word Memory Test, a PVT. A restricted regression model, including
      education, age, history of loss of consciousness, cognitive measures, and a
      measure of symptom validity test performance, was not significantly associated
      with self-reported community reintegration. Adding PVT results to the restricted
      model, however, did significantly improve the prediction of community
      reintegration as PVT failure was associated with lower self-reported community
      participation. The results of this study indicate that PVTs may also serve as an
      indicator of patients' functioning in the community. 

PMID- 24681944
TI  - Spin biochemistry modulates reactive oxygen species (ROS) production by radio
      frequency magnetic fields.
AB  - The effects of weak magnetic fields on the biological production of reactive
      oxygen species (ROS) from intracellular superoxide (O2*-) and extracellular
      hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial
      smooth muscle cells (rPASMC). A decrease in O2*- and an increase in H2O2
      concentrations were observed in the presence of a 7 MHz radio frequency (RF) at
      10 MUTRMS and static 45 MUT magnetic fields. We propose that O2*- and H2O2
      production in some metabolic processes occur through singlet-triplet modulation
      of semiquinone flavin (FADH*) enzymes and O2*- spin-correlated radical pairs.
      Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that
      presumably decouple flavin hyperfine interactions during spin coherence. RF
      flavin hyperfine decoupling results in an increase of H2O2 singlet state
      products, which creates cellular oxidative stress and acts as a secondary
      messenger that affects cellular proliferation. This study demonstrates the
      interplay between O2*- and H2O2 production when influenced by RF magnetic fields
      and underscores the subtle effects of low-frequency magnetic fields on oxidative
      metabolism, ROS signaling, and cellular growth. 

PMID- 24681946
TI  - SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that has a
      central role in the regulation of tumour metabolism under hypoxic conditions. HIF
      1alpha stimulates glycolytic energy production and promotes tumour growth.
      Sirtuins are NAD(+)-dependent protein deacetylases that regulate cellular
      metabolism in response to stress; however, their involvement in the hypoxic
      response remains unclear. In this study, it is shown that SIRT2-mediated
      deacetylation of HIF-1alpha regulates its stability in tumour cells. SIRT2
      overexpression destabilized HIF-1alpha under hypoxic conditions, whereas HIF
      1alpha protein levels were high in SIRT2-deficient cells. SIRT2 directly
      interacted with HIF-1alpha and deacetylated Lys709 of HIF-1alpha. Deacetylation
      of HIF-1alpha by SIRT2 resulted in increased binding affinity for prolyl
      hydroxylase 2, a key regulator of HIF-1alpha stability, and increased HIF-1alpha
      hydroxylation and ubiquitination. Moreover, a pharmacological agent that
      increased the intracellular NAD(+)/NADH ratio led to the degradation of HIF
      1alpha by increasing SIRT2-mediated deacetylation and subsequent hydroxylation.
      These findings suggest that SIRT2-mediated HIF-1alpha deacetylation is critical
      for the destablization of HIF-1alpha and the hypoxic response of tumour cells. 

PMID- 24681947
TI  - EGF inhibits constitutive internalization and palmitoylation-dependent
      degradation of membrane-spanning procancer CDCP1 promoting its availability on
      the cell surface.
AB  - Many cancers are dependent on inappropriate activation of epidermal growth factor
      receptor (EGFR), and drugs targeting this receptor can improve patient survival,
      although benefits are generally short-lived. We reveal a novel mechanism linking
      EGFR and the membrane-spanning, cancer-promoting protein CDCP1 (CUB domain
      containing protein 1). Under basal conditions, cell surface CDCP1 constitutively
      internalizes and undergoes palmitoylation-dependent degradation by a mechanism in
      which it is palmitoylated in at least one of its four cytoplasmic cysteines. This
      mechanism is functional in vivo as CDCP1 is elevated and palmitoylated in high
      grade serous ovarian tumors. Interestingly, activation of the EGFR system with
      EGF inhibits proteasome-mediated, palmitoylation-dependent degradation of CDCP1,
      promoting recycling of CDCP1 to the cell surface where it is available to mediate
      its procancer effects. We also show that mechanisms inducing relocalization of
      CDCP1 to the cell surface, including disruption of its palmitoylation and EGF
      treatment, promote cell migration. Our data provide the first evidence that the
      EGFR system can function to increase the lifespan of a protein and also promote
      its recycling to the cell surface. This information may be useful for
      understanding mechanisms of resistance to EGFR therapies and assist in the design
      of treatments for EGFR-dependent cancers. 

PMID- 24681948
TI  - A targeted knockdown screen of genes coding for phosphoinositide modulators
      identifies PIP4K2A as required for acute myeloid leukemia cell proliferation and
      survival.
AB  - Given the importance of deregulated phosphoinositide (PI) signaling in leukemic
      hematopoiesis, genes coding for proteins that regulate PI metabolism may have
      significant and as yet unappreciated roles in leukemia. We performed a targeted
      knockdown (KD) screen of PI modulator genes in human acute myeloid leukemia (AML)
      cells and identified candidates required to sustain proliferation or prevent
      apoptosis. One of these, the lipid kinase phosphatidylinositol-5-phosphate 4
      kinase, type II, alpha (PIP4K2A) regulates cellular levels of
      phosphatidylinositol-5-phosphate (PtsIns5P) and phosphatidylinositol 4,5
      bisphosphate (PtdIns(4,5)P2). We found PIP4K2A to be essential for the clonogenic
      and leukemia-initiating potential of human AML cells, and for the clonogenic
      potential of murine MLL-AF9 AML cells. Importantly, PIP4K2A is also required for
      the clonogenic potential of primary human AML cells. Its KD results in
      accumulation of the cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, G1 cell
      cycle arrest and apoptosis. Both CDKN1A accumulation and apoptosis were partially
      dependent on activation of the mTOR pathway. Critically, however, PIP4K2A KD in
      normal hematopoietic stem and progenitor cells, both murine and human, did not
      adversely impact either clonogenic or multilineage differentiation potential,
      indicating a selective dependency that we suggest may be the consequence of the
      regulation of different transcriptional programs in normal versus malignant
      cells. Thus, PIP4K2A is a novel candidate therapeutic target in myeloid
      malignancy.

PMID- 24681949
TI  - Regulation of the mitogen-activated protein kinase kinase (MEK)-1 by NAD(+)
      dependent deacetylases.
AB  - Sirtuins are class III deacetylases that regulate many essential processes,
      including cellular stress, genome stability and metabolism. Although these NAD(+)
      dependent deacetylases control adaptive cellular responses, identification of
      sirtuin-regulated signaling targets remain under-studied. Here, we demonstrate
      that acetylation of the mitogen-activated protein kinase kinase-1 (MEK1)
      stimulates its kinase activity, and that acetylated MEK1 is under the regulatory
      control of the sirtuin family members SIRT1 and SIRT2. Treatment of cells with
      sirtuin inhibitors, or siRNA knockdown of SIRT1 or SIRT2 proteins, increases MEK1
      acetylation and subsequent phosphorylation of the extracellular signal-regulated
      kinase. Generation of an acetyl-specific MEK1 antibody demonstrates that
      endogenous acetylated MEK1 is extensively enriched in the nucleus following
      epidermal growth factor  stimulation. An acetyl-mimic of MEK1 increases
      inappropriate growth properties, suggesting that acetylation of MEK1 has
      oncogenic potential. 

PMID- 24681950
TI  - A novel mechanism for the control of translation of specific mRNAs by tumor
      suppressor protein Pdcd4: inhibition of translation elongation.
AB  - The tumor suppressor gene Pdcd4 (programmed cell death gene 4) has drawn
      considerable attention because its downregulation is involved in the development
      of several types of cancer. Because Pdcd4 interacts with the translation
      initiation factor eIF4A and inhibits its helicase activity, Pdcd4 has been
      implicated in the translational suppression of cellular mRNAs containing
      structured 5'-untranslated regions. However, Pdcd4's role in translation
      regulation is still poorly understood, because only very few physiological Pdcd4
      target mRNAs are known. By using a Pdcd4-deficient clone of the chicken B-cell
      line DT40, we have discovered that the mRNA of the A-myb proto-oncogene is a
      novel Pdcd4 target RNA whose translation is suppressed by Pdcd4. Interestingly,
      the inhibitory effect of Pdcd4 is independent of the Pdcd4-eIF4A interaction, but
      is dependent on an RNA-binding domain at the N terminus of Pdcd4 and on sequences
      located within the coding region of A-myb mRNA, indicating that Pdcd4 suppresses
      A-myb translation by a novel mechanism. Our data show that the Pdcd4 RNA-binding
      domain preferentially recognizes an RNA secondary structure element formed by the
      part of the A-myb coding region that mediates Pdcd4-dependent suppression.
      Previously, we have shown that Pdcd4 also suppresses the translation of the c-myb
      mRNA by a similar mechanism involving binding of Pdcd4 to RNA secondary structure
      formed by the c-myb coding region. Surprisingly, our data show that Pdcd4 exerts
      its inhibitory activity only when the target region of Pdcd4 in A-myb and c-myb
      mRNA is itself translated, consistent with a mechanism in which Pdcd4 suppresses
      translation by interfering with translation elongation. Taken together, our work
      reveals a novel mechanism by which Pdcd4 affects the translational of cellular
      RNAs. Furthermore, as c-myb and A-myb are members of the Myb proto-oncogene
      family whose deregulation has been implicated in tumorigenesis, inhibiting their
      translation might contribute to the tumor-suppressive activity of Pdcd4. 

PMID- 24681951
TI  - Decreased TIP30 promotes Snail-mediated epithelial-mesenchymal transition and
      tumor-initiating properties in hepatocellular carcinoma.
AB  - The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to tumor
      recurrence and metastases. Recently, epithelial-mesenchymal transition (EMT) has
      been implicated in tumor invasion and metastasis. However, the underlying
      molecular mechanisms are yet to be elucidated. Here, we show that 30-kDa Tat
      interacting protein (TIP30), also called CC3, is significantly downregulated
      during transforming growth factor-beta-induced EMT. In our in vitro and in vivo
      studies, we show that decreased TIP30 expression leads to EMT, as well as
      enhanced motility and invasion of HCC cells. Also, increased self-renewal ability
      and chemotherapeutic resistance are observed with TIP30 depletion. Moreover,
      Snail is one of the key transcription factors promoting EMT, and overexpression
      of TIP30 greatly decreased nucleic accumulation in Snail through the regulation
      of intracellular localization. Small interfering RNAs targeting Snail attenuated
      EMT and tumor-initiating properties induced by TIP30 deficiency. We further
      confirmed that TIP30 competitively interrupted the interaction of Snail with
      importin-beta2 to block the nuclear import of Snail. Consistently, TIP30
      expression significantly correlates with E-cadherin expression in HCC patients.
      TIP30 or combination of E-cadherin is a powerful marker in predicting the
      prognosis of HCC. Taken together, our results suggest a novel and critical role
      of TIP30 involved in HCC progression and aggressiveness. 

PMID- 24681952
TI  - PATHOME: an algorithm for accurately detecting differentially expressed
      subpathways.
AB  - The translation of high-throughput gene expression data into biologically
      meaningful information remains a bottleneck. We developed a novel computational
      algorithm, PATHOME, for detecting differentially expressed biological pathways.
      This algorithm employs straightforward statistical tests to evaluate the
      significance of differential expression patterns along subpathways. Applying it
      to gene expression data sets of gastric cancer (GC), we compared its performance
      with those of other leading programs. Based on a literature-driven reference set,
      PATHOME showed greater consistency in identifying known cancer-related pathways.
      For the WNT pathway uniquely identified by PATHOME, we validated its involvement
      in gastric carcinogenesis through experimental perturbation of both cell lines
      and animal models. We identified HNF4alpha-WNT5A regulation in the cross-talk
      between the AMPK metabolic pathway and the WNT signaling pathway, and further
      identified WNT5A as a potential therapeutic target for GC. We have demonstrated
      PATHOME to be a powerful tool, with improved sensitivity for identifying disease
      related dysregulated pathways. 

PMID- 24681953
TI  - Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene
      regulation.
AB  - STAT (Signal Transducer and Activator of Transcription) transcription factors are
      constitutively activated in most hematopoietic cancers. We previously identified
      a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner
      in lipoma), induced by constitutive activation of STAT5, but not by transient
      cytokine-activated STAT5. miR-28 exerts negative effects on thrombopoietin
      receptor signaling and platelet formation. Here, we demonstrate that, in
      transformed hematopoietic cells, STAT5 and p53 must be synergistically bound to
      chromatin for induction of LPP/miR-28 transcription. Genome-wide association
      studies show that both STAT5 and p53 are co-localized on the chromatin at 463
      genomic positions in proximal promoters. Chromatin binding of p53 is dependent on
      persistent STAT5 activation at these proximal promoters. The transcriptional
      activity of selected promoters bound by STAT5 and p53 was significantly changed
      upon STAT5 or p53 inhibition. Abnormal expression of several STAT5-p53 target
      genes (LEP, ATP5J, GTF2A2, VEGFC, NPY1R and NPY5R) is frequently detected in
      platelets of myeloproliferative neoplasm (MPN) patients, but not in platelets
      from healthy controls. In conclusion, persistently active STAT5 can recruit
      normal p53, like in the case of MPN cells, but also p53 mutants, such as p53
      M133K in human erythroleukemia cells, leading to pathologic gene expression that
      differs from canonical STAT5 or p53 transcriptional programs. 

PMID- 24681954
TI  - The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively
      regulates PKC-mediated signaling pathway.
AB  - The receptor for activated C-kinase (RACK1), a scaffolding protein that
      participates in the protein kinase C (PKC) signaling pathway, has an important
      role in shuttling active PKCs to its substrate. Indeed, recent studies have
      revealed that RACK1 has an important role in tumorigenesis and that enhancement
      of the feed-forward mechanism of the c-Jun N-terminal kinase (JNK)-Jun pathway
      via RACK1 is associated with constitutive activation of MEK (MAPK-ERK kinase)-ERK
      (extracellular signal-regulated kinase) signaling in human melanoma cells. Taken
      together, RACK1 additionally has a very important role in the mitogen-activated
      protein kinase (MAPK) signaling pathway. Here, we show that one of the tripartite
      motif-containing (TRIM) family ubiquitin ligases, TRIM45, is a novel RACK1
      interacting protein and downregulates MAPK signal transduction. Importantly, the
      expression of TRIM45 is induced when growth-promoting extracellular stimuli
      activate the MAPK signaling pathway, resulting in attenuation of activation of
      the MAPK pathway. These findings suggest that TRIM45 functions as a member of the
      negative feedback loop of the MAPK pathway. 

PMID- 24681956
TI  - B-cell lymphoma/leukemia 10 promotes oral cancer progression through
      STAT1/ATF4/S100P signaling pathway.
AB  - B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to
      advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC).
      However, the regulatory mechanism of BCL10 in OSCC progression is still unknown.
      Here, we showed that knockdown of endogenous BCL10 could significantly reduce
      cell migration and invasion abilities, retard cell proliferation by G0/G1 phase
      accumulation and inhibit tumorigenicity in vivo. In molecular level, we
      identified S100P as a crucial downstream effector of BCL10-inhibited OSCC
      progression by high-throughput microarray analysis. S100P messenger RNA and
      protein expression levels were significantly diminished in silenced-BCL10 clones,
      and transfected S100P expression plasmids restored migration, invasion,
      proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore,
      we provided evidence that BCL10 regulated S100P expression through signal
      transducers and activators of transcription 1 (STAT1) and activating
      transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter
      activity, but showed no effect in truncated STAT1/ATF4 S100P promoter.  In
      addition, we also found that the P50/P65 signaling pathway was involved in BCL10
      enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly
      reverse P65 activation via outside-in signaling. Taken together, we discovered a
      novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65
      signaling, which could predict the prognosis of OSCC and will be beneficial for
      developing therapeutic strategy against advanced OSCC. 

PMID- 24681955
TI  - SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating
      cells.
AB  - Melanoma is one of the most aggressive types of human cancer, characterized by
      enhanced heterogeneity and resistance to conventional therapy at advanced stages.
      We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is
      required for melanoma growth and for survival and expansion of melanoma
      initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates
      a set of genes typically expressed in embryonic stem cells, including SOX2 (sex
      determining region Y (SRY)-Box2). Here we address the function of SOX2 in human
      melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2
      is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases
      self-renewal in melanoma spheres and in putative melanoma stem cells with high
      aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of
      SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also
      inhibits cell growth and induces apoptosis in melanoma cells. In addition,
      depletion of SOX2 progressively abrogates tumor growth and leads to a significant
      decrease in tumor-initiating capability of ALDH(high) MICs upon
      xenotransplantation, suggesting that SOX2 is required for tumor initiation and
      for continuous tumor growth. We show that SOX2 is regulated by HH signaling and
      that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI
      signaling, bind to the proximal promoter region of SOX2 in primary melanoma
      cells. In functional studies, we find that SOX2 function is required for HH
      induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a
      critical factor for self-renewal and tumorigenicity of MICs and an important
      mediator of HH-GLI signaling in melanoma. These findings could provide the basis
      for novel therapeutic strategies based on the inhibition of SOX2 for the
      treatment of a subset of human melanomas. 

PMID- 24681957
TI  - The Parkinson's gene PINK1 regulates cell cycle progression and promotes cancer
      associated phenotypes.
AB  - PINK1 (phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced
      kinase 1), a Parkinson's disease-associated gene, was identified originally
      because of its induction by the tumor-suppressor PTEN. PINK1 promotes cell
      survival and potentially metastatic functions and protects against cell stressors
      including chemotherapeutic agents. However, the mechanisms underlying PINK1
      function in cancer cell biology are unclear. Here, using several model systems,
      we show that PINK1 deletion significantly reduced cancer-associated phenotypes
      including cell proliferation, colony formation and invasiveness, which were
      restored by human PINK1 overexpression. Results show that PINK1 deletion causes
      major defects in cell cycle progression in immortalized mouse embryonic
      fibroblasts (MEFs) from PINK1(-/-) mice, and in BE(2)-M17 cells stably transduced
      with short hairpin RNA against PINK1. Detailed cell cycle analyses of MEF cell
      lines from several PINK1(-/-) mice demonstrate an increased proportion of cells
      in G2/M and decreased number of cells in G1 following release from nocodazole
      block. This was concomitant with increased double and multi-nucleated cells, a
      reduced ability to undergo cytokinesis and to re-enter G1, and significant
      alterations in cell cycle markers, including failure to increase cyclin D1, all
      indicative of mitotic arrest. PINK1(-/-) cells also demonstrated ineffective cell
      cycle exit following serum deprivation. Cell cycle defects associated with PINK1
      deficiency occur at points critical for cell division, growth and stress
      resistance in cancer cells were rescued by ectopic expression of human PINK1 and
      demonstrated PINK1 kinase dependence. The importance of PINK1 for cell cycle
      control is further supported by results showing that cell cycle deficits induced
      by PINK1 deletion were linked mechanistically to aberrant mitochondrial fission
      and its regulation by dynamin-related protein-1 (Drp1), known to be critical for
      progression of mitosis. Our data indicate that PINK1 has tumor-promoting
      properties and demonstrates a new function for PINK1 as a regulator of the cell
      cycle. 

PMID- 24681958
TI  - High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel
      binding targets and prognostic role for SOX11 in mantle cell lymphoma.
AB  - Sex determining region Y-box 11 (SOX11) expression is specific for mantle cell
      lymphoma (MCL) as compared with other non-Hodgkin's lymphomas. However, the
      function and direct-binding targets of SOX11 in MCL are largely unknown. We used
      high-resolution chromatin immunoprecipitation sequencing to identify the direct
      target genes of SOX11 in a genome-wide, unbiased manner and elucidate its
      functional significance. Pathway analysis identified WNT, PKA and TGF-beta
      signaling pathways as significantly enriched by SOX11-target genes. Quantitative
      chromatin immunoprecipitation sequencing and promoter reporter assays confirmed
      that SOX11 directly binds to individual genes and modulates their transcription
      activities in these pathways in MCL. Functional studies using RNA interference
      demonstrate that SOX11 directly regulates WNT in MCL. We analyzed SOX11
      expression in three independent well-annotated tissue microarrays from the
      University of Wisconsin (UW), Karolinska Institute and British Columbia Cancer
      Agency. Our findings suggest that high SOX11 expression is associated with
      improved survival in a subset of MCL patients, particularly those treated with
      intensive chemotherapy. Transcriptional regulation of WNT and other biological
      pathways affected by SOX11-target genes may help explain the impact of SOX11
      expression on patient outcomes. 

PMID- 24681960
TI  - Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III
      guidelines, and European Society of Cardiology guidelines for cardiovascular
      disease prevention in a European cohort.
AB  - IMPORTANCE: The 2013 American College of Cardiology/American Heart Association
      (ACC/AHA) guidelines introduced a prediction model and lowered the threshold for
      treatment with statins to a 7.5% 10-year hard atherosclerotic cardiovascular
      disease (ASCVD) risk. Implications of the new guideline's threshold and model
      have not been addressed in non-US populations or compared with previous
      guidelines. OBJECTIVE: To determine population-wide implications of the ACC/AHA,
      the Adult Treatment Panel III (ATP-III), and the European Society of Cardiology
      (ESC) guidelines using a cohort of Dutch individuals aged 55 years or older.
      DESIGN, SETTING, AND PARTICIPANTS: We included 4854 Rotterdam Study participants
      recruited in 1997-2001. We calculated 10-year risks for "hard" ASCVD events
      (including fatal and nonfatal coronary heart disease [CHD] and stroke) (ACC/AHA),
      hard CHD events (fatal and nonfatal myocardial infarction, CHD mortality) (ATP
      III), and atherosclerotic CVD mortality (ESC). MAIN OUTCOMES AND MEASURES: Events
      were assessed until January 1, 2012. Per guideline, we calculated proportions of
      individuals for whom statins would be recommended and determined calibration and
      discrimination of risk models. RESULTS: The mean age was 65.5 (SD, 5.2) years.
      Statins would be recommended for 96.4% (95% CI, 95.4%-97.1%; n = 1825) of men and
      65.8% (95% CI, 63.8%-67.7%; n = 1523) of women by the ACC/AHA, 52.0% (95% CI,
      49.8%-54.3%; n = 985) of men and 35.5% (95% CI, 33.5%-37.5%; n = 821) of women by
      the ATP-III, and 66.1% (95% CI, 64.0%-68.3%; n = 1253) of men and 39.1% (95% CI,
      37.1%-41.2%; n = 906) of women by ESC guidelines. With the ACC/AHA model, average
      predicted risk vs observed cumulative incidence of hard ASCVD events was 21.5%
      (95% CI, 20.9%-22.1%) vs 12.7% (95% CI, 11.1%-14.5%) for men (192 events) and
      11.6% (95% CI, 11.2%-12.0%) vs 7.9% (95% CI, 6.7%-9.2%) for women (151 events).
      Similar overestimation occurred with the ATP-III model (98 events in men and 62
      events in women) and ESC model (50 events in men and 37 events in women). The C
      statistic was 0.67 (95% CI, 0.63-0.71) in men and 0.68 (95% CI, 0.64-0.73) in
      women for hard ASCVD (ACC/AHA), 0.67 (95% CI, 0.62-0.72) in men and 0.69 (95% CI,
      0.63-0.75) in women for hard CHD (ATP-III), and 0.76 (95% CI, 0.70-0.82) in men
      and 0.77 (95% CI, 0.71-0.83) in women for CVD mortality (ESC). CONCLUSIONS AND
      RELEVANCE: In this European population aged 55 years or older, proportions of
      individuals eligible for statins differed substantially among the guidelines. The
      ACC/AHA guideline would recommend statins for nearly all men and two-thirds of
      women, proportions exceeding those with the ATP-III or ESC guidelines. All 3 risk
      models provided poor calibration and moderate to good discrimination. Improving
      risk predictions and setting appropriate population-wide thresholds are necessary
      to facilitate better clinical decision making.

PMID- 24681961
TI  - 5-Azacytidine treatment sensitizes tumor cells to T-cell mediated cytotoxicity
      and modulates NK cells in patients with myeloid malignancies.
AB  - Treatment with the demethylating agent 5-Azacytidine leads to prolonged survival
      for patients with myelodysplastic syndrome, and the demethylation induces
      upregulation of cancer-testis antigens. Cancer-testis antigens are well-known
      targets for immune recognition in cancer, and the immune system may have a role
      in this treatment regimen. We show here that 5-Azacytidine treatment leads to
      increased T-cell recognition of tumor cells. T-cell responses against a large
      panel of cancer-testis antigens were detected before treatment, and these
      responses were further induced upon initiation of treatment. These
      characteristics point to an ideal combination of 5-Azacytidine and immune therapy
      to preferentially boost T-cell responses against cancer-testis antigens. To
      initiate such combination therapy, essential knowledge is required about the
      general immune modulatory effect of 5-Azacytidine. We therefore examined
      potential treatment effects on both immune stimulatory (CD8 and CD4 T cells and
      Natural Killer (NK) cells) and immune inhibitory cell subsets (myeloid-derived
      suppressor cells and regulatory T cells). We observed a minor decrease and
      modulation of NK cells, but for all other populations no effects could be
      detected. Together, these data support a strategy for combining 5-Azacytidine
      treatment with immune therapy for potential clinical benefit. 

PMID- 24681959
TI  - Drug-repositioning screening identified piperlongumine as a direct STAT3
      inhibitor with potent activity against breast cancer.
AB  - Signal transducer and activator of transcription (STAT) 3 regulates many cardinal
      features of cancer including cancer cell growth, apoptosis resistance, DNA damage
      response, metastasis, immune escape, tumor angiogenesis, the Warburg effect and
      oncogene addiction and has been validated as a drug target for cancer therapy.
      Several strategies have been used to identify agents that target Stat3 in breast
      cancer but none has yet entered into clinical use. We used a high-throughput
      fluorescence microscopy search strategy to identify compounds in a drug
      repositioning library (Prestwick library) that block ligand-induced nuclear
      translocation of Stat3 and identified piperlongumine (PL), a natural product
      isolated from the fruit of the pepper Piper longum. PL inhibited Stat3 nuclear
      translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation,
      and modulated expression of multiple Stat3-regulated genes. Surface plasmon
      resonance assay revealed that PL directly inhibited binding of Stat3 to its
      phosphotyrosyl peptide ligand. Phosphoprotein antibody array analysis revealed
      that PL does not modulate kinases known to activate Stat3 such as Janus kinases,
      Src kinase family members or receptor tyrosine kinases. PL inhibited anchorage
      independent and anchorage-dependent growth of multiple breast cancer cell lines
      having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited
      mammosphere formation by tumor cells from patient-derived xenografts. PL's
      antitumorigenic function was causally linked to its Stat3-inhibitory effect. PL
      was non-toxic in mice up to a dose of 30 mg/kg/day for 14 days and caused
      regression of breast cancer cell line xenografts in nude mice. Thus, PL
      represents a promising new agent for rapid entry into the clinic for use in
      treating breast cancer, as well as other cancers in which Stat3 has a role. 

PMID- 24681962
TI  - Novel function of the chromosome 7 open reading frame 41 gene to promote leukemic
      megakaryocyte differentiation by modulating TPA-induced signaling.
AB  - 12-O-tetradecanoylphorbol-13-acetate (TPA) activates multiple signaling pathways,
      alters gene expression and causes leukemic cell differentiation. How TPA-induced
      genes contribute to leukemic cell differentiation remains elusive. We noticed
      that chromosome 7 open reading frame 41 (C7ORF41) was a TPA-responsive gene and
      its upregulation concurred with human megakaryocyte differentiation. In K562
      cells, ectopic expression of C7ORF41 significantly increased CD61 expression,
      enhanced ERK and JNK signaling, and upregulated RUNX1 and FLI1, whereas C7ORF41
      knockdown caused an opposite phenotype. These observations suggest that C7ORF41
      may promote megakaryocyte differentiation partially through modulating ERK and
      JNK signaling that leads to upregulation of RUNX1 and FLI1. In supporting this,
      C7ORF41 overexpression rescued megakaryocyte differentiation blocked by ERK
      inhibition while JNK inhibition abrogated the upregulation of FLI1 by C7ORF41.
      Furthermore, we found that Y34F mutant C7ORF41 inhibited megakaryocyte
      differentiation. nuclear factor kappa-light-chain-enhancer of activated B cells
      (NF-kappaB) was the major activator of C7ORF41 that in turn repressed NF-kappaB
      activity by inhibiting its phosphorylation at serine 536, while MAPK/ERK was the
      potent repressor of C7ORF41. Finally, we showed that C7ORF41 knockdown in mouse
      fetal liver cells impaired megakaryocyte differentiation. Taken together, we have
      identified the function of a novel gene C7ORF41 that forms interplaying
      regulatory network in TPA-induced signaling and promotes leukemic and normal
      megakaryocyte differentiation. 

PMID- 24681963
TI  - The effects of a Gly16Arg ADRB2 polymorphism on responses to salmeterol or
      montelukast in Japanese patients with mild persistent asthma.
AB  - BACKGROUND: Long-acting beta2-agonists and leukotriene receptor antagonists are
      two principal agents that can be added to inhaled corticosteroids (ICS) for
      patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg
      genotype of the beta2-adrenergic receptor (ADRB2) gene may influence the
      bronchodilator effects of beta2-agonists. We hypothesized that differential
      responses to long-acting beta2-agonists or leukotriene receptor antagonists might
      be determined partly by the Gly16Arg polymorphism in Japanese asthma patients.
      MATERIALS AND METHODS: This randomized, genotype-stratified, two-period crossover
      study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45
      Gly/Gly individuals). The primary study outcome was the difference in peak
      expiratory flow (DeltaPEF) (DeltaPEF, l/min) by genotype after 16 weeks of
      treatment with salmeterol (DeltaPEFsal) or montelukast (DeltaPEFmon). In
      addition, multivariate analyses were used to identify independent factors that
      were predictive of responses to each treatment. RESULTS: The mean DeltaPEFsal
      DeltaPEFmon was 19.3+/-46.6 among Arg/Arg individuals and 16.8+/-51.5 among
      Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the
      differential bronchodilator effect of the two agents. Multivariate analysis
      showed that higher peripheral eosinophil counts were associated with better
      response to salmeterol (P<0.05). CONCLUSION: The Gly16Arg genotype did not
      influence the differential bronchodilator effect of salmeterol or montelukast as
      an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral
      eosinophil counts may be associated with better responses to salmeterol in
      combination with ICS.

PMID- 24681964
TI  - Associations between polymorphisms in target, metabolism, or transport proteins
      of mycophenolate sodium and therapeutic or adverse effects in kidney transplant
      patients.
AB  - OBJECTIVES: Different associations between single nucleotide polymorphisms (SNPs)
      in cellular target, metabolism enzymes or transport proteins, and biopsy-proven
      acute rejection (BPAR) or adverse events have been reported in transplant
      patients receiving mycophenolate mofetil. This work aimed to study these in
      patients on enteric-coated mycophenolate sodium (EC-MPS). PATIENTS AND METHODS:
      The study included 189 renal transplant patients from the DOMINOS trial. Fifteen
      SNPs in IMPDH2, IMPDH1, ABCC2, SLCO1B3, UGT1A8, UGT1A9, UGT2B7, CYP2C8, HUS1, and
      IL12A were genotyped in all patients. Associations between SNPs and the first
      event of BPAR or diarrhea were investigated using multivariate logistic
      regressions. Associations between SNPs and leukopenia or anemia at nine different
      visits between days 0 and 190 after transplantation were studied using time
      dependent Cox proportional hazards regression models. RESULTS: Multivariate
      analyses showed that the CYP2C8 rs11572076 wild-type genotype was associated
      significantly with a lower risk of leukopenia [GG vs. GA: hazard ratio (95%
      confidence interval) 0.14 (0.03, 0.59), P=0.00783]. Higher EC-MPS doses and the
      UGT2B7 c.-840 G>A variant allele were associated with an increased risk of anemia
      [EC-MPS per unit dose increase: 1.004 (1.003, 1.005), P<0.0001; UGT2B7 GA vs. AA:
      1.65 (1.12, 2.43), P=0.01043; GG vs. AA: 1.88 (1.23, 2.88), P=0.00343]. However,
      no significant association was found between any of the SNPs studied and diarrhea
      or BPAR. CONCLUSION: Two pharmacogenetic associations reported previously with
      mycophenolate mofetil were found in a population of 189 renal transplant patients
      treated with EC-MPS.

PMID- 24681965
TI  - PharmGKB summary: very important pharmacogene information for SLC22A1.

PMID- 24681966
TI  - In vitro characterization of 6S RNA release-defective mutants uncovers features
      of pRNA-dependent release from RNA polymerase in E. coli.
AB  - 6S RNA is a noncoding RNA that inhibits bacterial transcription by sequestering
      RNA polymerase holoenzyme (Esigma(70)) in low-nutrient conditions. This
      transcriptional block can be relieved by the synthesis of a short product RNA
      (pRNA) using the 6S RNA as a template. Here, we selected a range of 6S RNA
      release-defective mutants from a high diversity in vitro pool. Studying the
      release-defective variant R9-33 uncovered complex interactions between three
      regions of the 6S RNA. As expected, mutating the transcriptional start site (TSS)
      slowed and partially inhibited release. Surprisingly, additional mutations near
      the TSS were found that rescued this effect. Likewise, three mutations in the top
      strand of the large open bubble (LOB) could considerably slow release but were
      rescued by the addition of upstream mutations found between a highly conserved "
      35" motif and the LOB. Combining the three top strand LOB mutations with
      mutations near the TSS, however, was particularly effective at preventing
      release, and this effect could be further enhanced by inclusion of the upstream
      mutations. Overexpressing R9-33 and a series of milder release-defective mutants
      in Escherichia coli resulted in a delayed entry into exponential phase together
      with a decrease in cell survival that correlated well with the severity of the in
      vitro phenotypes. The complex crosstalk observed between distinct regions of the
      6S RNA supports a scrunching type model of 6S RNA release, where at least three
      regions of the 6S RNA must interact with Esigma(70) in a cooperative manner so as
      to ensure effective pRNA-dependent release. 

PMID- 24681967
TI  - The crystal structure of S. cerevisiae Sad1, a catalytically inactive
      deubiquitinase that is broadly required for pre-mRNA splicing.
AB  - Sad1 is an essential splicing factor initially identified in a genetic screen in
      Saccharomyces cerevisiae for snRNP assembly defects. Based on sequence homology,
      Sad1, or USP39 in humans, is predicted to comprise two domains: a zinc finger
      ubiquitin binding domain (ZnF-UBP) and an inactive ubiquitin-specific protease
      (iUSP) domain, both of which are well conserved. The role of these domains in
      splicing and their interaction with ubiquitin are unknown. We first used splicing
      microarrays to analyze Sad1 function in vivo and found that Sad1 is critical for
      the splicing of nearly all yeast intron-containing genes. By using in vitro
      assays, we then showed that it is required for the assembly of the active
      spliceosome. To gain structural insights into Sad1 function, we determined the
      crystal structure of the full-length protein at 1.8 A resolution. In the
      structure, the iUSP domain forms the characteristic ubiquitin binding pocket,
      though with an amino acid substitution in the active site that results in
      complete inactivation of the enzymatic activity of the domain. The ZnF-UBP domain
      of Sad1 shares high structural similarly to other ZnF-UBPs; however, Sad1's ZnF
      UBP does not possess the canonical ubiquitin binding motif. Given the precedents
      for ZnF-UBP domains to function as activators for their neighboring USP domains,
      we propose that Sad1's ZnF-UBP acts in a ubiquitin-independent capacity to
      recruit and/or activate Sad1's iUSP domain to interact with the spliceosome. 

PMID- 24681969
TI  - The association between sleep disturbance, depressive symptoms, and health
      related quality of life among cardiac rehabilitation participants.
AB  - PURPOSE: Recent guidelines from the Canadian Association of Cardiac
      Rehabilitation highlight the importance of addressing sleep disturbance among
      participants of cardiac rehabilitation (CR) programs. The primary objective of
      this study was to examine the relationship between depressive symptoms, health
      related quality of life, and sleep disturbance in CR participants. The secondary
      objective was to estimate the prevalence of sleep disturbance among CR
      participants with and without depressive symptoms and explore demographic,
      medical, and psychological predictors of poor sleep quality. METHODS: Cardiac
      rehabilitation participants (N = 259) were included in this study. Participants
      completed a standardized questionnaire package including demographic, health
      related, and psychosocial measures. Physiologic and anthropometric measurements
      were taken at baseline. Descriptive statistics were calculated for all variables,
      and data were analyzed using multivariate logistic regression. RESULTS: Poor
      sleep quality was reported by 52% of participants in the sample, and 47% of
      participants in the sample reported experiencing at least mild depressive
      symptoms. Poor sleep occurred more often in individuals with depressive symptoms,
      and after adjustment for medical factors and health-related quality of life,
      participants with symptoms of depression were still more likely to experience
      sleep disturbance than those without depressive symptoms (OR = 2.80; 95% CI, 1.37
      5.77). An important gender difference emerged in the relationship between
      symptoms of depression and sleep disturbance. CONCLUSION: Among participants of a
      CR program, disturbed sleep was strongly associated with depressive symptoms and
      decreased health-related quality of life. Results demonstrate the importance of
      sleep evaluation in CR programs.

PMID- 24681968
TI  - The beta-actin mRNA zipcode regulates epithelial adherens junction assembly but
      not maintenance.
AB  - Epithelial cell-cell contact stimulates actin cytoskeleton remodeling to down
      regulate branched filament polymerization-driven lamellar protrusion and
      subsequently to assemble linear actin filaments required for E-cadherin anchoring
      during adherens junction complex assembly. In this manuscript, we demonstrate
      that de novo protein synthesis, the beta-actin 3' UTR, and the beta-actin mRNA
      zipcode are required for epithelial adherens junction complex assembly but not
      maintenance. Specifically, we demonstrate that perturbing cell-cell contact
      localized beta-actin monomer synthesis causes epithelial adherens junction
      assembly defects. Consequently, inhibiting beta-actin mRNA zipcode/ZBP1
      interactions with beta-actin mRNA zipcode antisense oligonucleotides, to
      intentionally delocalize beta-actin monomer synthesis, is sufficient to perturb
      adherens junction assembly following epithelial cell-cell contact. Additionally,
      we demonstrate active RhoA, the signal required to drive zipcode-mediated beta
      actin mRNA targeting, is localized at epithelial cell-cell contact sites in a
      beta-actin mRNA zipcode-dependent manner. Moreover, chemically inhibiting Src
      kinase activity prevents the local stimulation of beta-actin monomer synthesis at
      cell-cell contact sites while inhibiting epithelial adherens junction assembly.
      Together, these data demonstrate that epithelial cell-cell contact stimulates
      beta-actin mRNA zipcode-mediated monomer synthesis to spatially regulate actin
      filament remodeling, thereby controlling adherens junction assembly to modulate
      cell and tissue adhesion. 

PMID- 24681970
TI  - Parents' experiences of raising pre-school aged children in an outer-Melbourne
      growth corridor.
AB  - There is growing concern about the outer-suburbs in Australia as healthy places
      to raise children. This paper aimed to explore this from the perspectives of
      parents raising preschool-age children in an outer-Melbourne municipality.
      Findings showed that parents were positive about the natural environment as well
      as the provision of recreation areas and generally felt their neighbourhoods were
      a safe place for raising children. However, car-dependency, housing estate design
      and limited local job opportunities all appeared to contribute to social
      isolation amongst families. Using the Environments for Health Framework, this
      paper makes suggestions to improve liveability for families in this municipality.

PMID- 24681971
TI  - Skeletal age estimation for forensic purposes: A comparison of GP, TW2 and TW3
      methods on an Italian sample.
AB  - BACKGROUND: Paediatricians, radiologists, anthropologists and medico-legal
      specialists are often called as experts in order to provide age estimation (AE)
      for forensic purposes. The literature recommends performing the X-rays of the
      left hand and wrist (HW-XR) for skeletal age estimation. The method most
      frequently employed is the Greulich and Pyle (GP) method. In addition, the so
      called bone-specific techniques are also applied including the method of Tanner
      Whitehouse (TW) in the latest versions TW2 and TW3. AIM: To compare skeletal age
      and chronological age in a large sample of children and adolescents using GP, TW2
      and TW3 methods in order to establish which of these is the most reliable for
      forensic purposes. MATERIAL AND METHODS: The sample consisted of 307 HW-XRs of
      Italian children or adolescents, 145 females and 162 males aged between 6 and 20
      years. The radiographies were scored according to the GP, TW2RUS and TW3RUS
      methods by one investigator. The results' reliability was assessed using
      intraclass correlation coefficient. Wilcoxon signed-rank test and Student t-test
      were performed to search for significant differences between skeletal and
      chronological ages. RESULTS: The distributions of the differences between
      estimated and chronological age, by means of boxplots, show how median
      differences for TW3 and GP methods are generally very close to 0. Hypothesis
      tests' results were obtained, with respect to the sex, both for the entire group
      of individuals and people grouped by age. Results show no significant differences
      among estimated and chronological age for TW3 and, to a lesser extent, GP. The
      TW2 proved to be the worst of the three methods. CONCLUSIONS: Our results support
      the conclusion that the TW2 method is not reliable for AE for forensic purpose.
      The GP and TW3 methods have proved to be reliable in males. For females, the best
      method was found to be TW3. When performing forensic age estimation in subjects
      around 14 years of age, it could be advisable to use and associate the TW3 and GP
      methods.

PMID- 24681972
TI  - Discrimination of human and animal blood traces via Raman spectroscopy.
AB  - The characterization of suspected blood stains is an important aspect of forensic
      science. In particular, determining the origin of a blood stain is a critical,
      yet overlooked, step in establishing its relevance to the crime. Currently,
      assays for determining human origin for blood are time consuming and destructive
      to the sample. The research presented here demonstrates that Raman spectroscopy
      can be effectively applied as a non-destructive technique for differentiating
      human blood from a wide survey of animal blood. A Partial Least Squares
      Discriminant Analysis (PLS-DA) model was built from a training set of the near
      infrared Raman spectra from 11 species. Various performance measures, including a
      blind test and external validation, confirm the discriminatory performance of the
      chemometric model. The model demonstrated 100% accuracy in its differentiation
      between human and nonhuman blood. These findings further demonstrate a great
      potential of Raman spectroscopy to the field of serology, especially for species
      identification of a suspected blood stain. 

PMID- 24681974
TI  - Health and Grandparent-Grandchild Well-Being: One-Year Longitudinal Findings for
      Custodial Grandfamilies.
AB  - OBJECTIVE: Comparatively little longitudinal data exist focusing on grandparent
      caregiving, to say nothing of health's impact over time on grandparent and
      grandchild well-being. Accordingly, the present study explored relationships
      among grandparent caregiver physical health, well-being, and adjustment, as well
      as with grandchild well-being across a 1-year period. METHOD: Participants were
      79 grandparents who had full-time responsibility for their grandchildren.
      Measures of grandparent physical health, well-being, and grandchild well-being
      were completed across two assessments, 1 year apart. RESULTS: Cross-lagged
      analyses exploring potential causality over time suggested that with one
      exception, the relationships between health and well-being appeared to be
      bidirectional. DISCUSSION: In general, these longitudinal data indicate that
      better perceived health may provide an adaptive advantage for both grandparent
      caregivers and their grandchildren, yet also underscore to the potentially causal
      role that proactivity in the face of adversity plays in the maintenance and
      improvement of grandparent caregiver health over time.

PMID- 24681973
TI  - Age-related macular degeneration and the incidence of cardiovascular disease: a
      systematic review and meta-analysis.
AB  - IMPORTANCE: Research has indicated some shared pathogenic mechanisms between age
      related macular degeneration (AMD) and cardiovascular disease (CVD). However,
      results from prior epidemiologic studies have been inconsistent as to whether AMD
      is predictive of future CVD risk. OBJECTIVE: To systematically review population
      based cohort studies of the association between AMD and risk of total CVD and CVD
      subtypes, coronary heart disease (CHD) and stroke. DATA SOURCES: A systematic
      search of the PubMed and EMBASE databases and reference lists of key retrieved
      articles up to December 20, 2012 without language restriction. DATA EXTRACTION:
      Two reviewers independently extracted data on baseline AMD status, risk estimates
      of CVD and methods used to assess AMD and CVD. We pooled relative risks using
      random or fixed effects models as appropriate. RESULTS: Thirteen cohort studies
      (8 prospective and 5 retrospective studies) with a total of 1,593,390
      participants with 155,500 CVD events (92,039 stroke and 62,737 CHD) were included
      in this meta-analysis. Among all studies, early AMD was associated with a 15%
      (95% CI, 1.08-1.22) increased risk of total CVD. The relative risk was similar
      but not significant for late AMD (RR, 1.17; 95% CI, 0.98-1.40). In analyses
      restricted to the subset of prospective studies, the risk associated with early
      AMD did not appreciably change; however, there was a marked 66% (95% CI, 1.31
      2.10) increased risk of CVD among those with late AMD. CONCLUSION: Whereas the
      results from all cohort studies suggest that both early and late AMD are
      predictive of a small increase in risk of future CVD, subgroup analyses limited
      to prospective studies demonstrate a markedly increased risk of CVD among people
      with late AMD. Retrospective studies using healthcare databases may have inherent
      methodological limitations that obscure such association. Additional prospective
      studies are needed to further elucidate the associations between AMD and specific
      CVD outcomes.

PMID- 24681975
TI  - Effects of Cognitive Speed of Processing Training Among Older Adults With Heart
      Failure.
AB  - OBJECTIVE: Cognitive deficits pose serious problems for older adults with heart
      failure (HF). Cognitive speed of processing training improves cognition among
      older adults but has not been examined among older adults with HF. METHOD: Data
      from the ACTIVE study were used to examine the effects of cognitive speed of
      processing training on cognitive and functional performance among older adults
      with HF. RESULTS: Of the 54 participants included in the analyses, 23 who were
      randomized to cognitive training performed significantly better on a composite of
      everyday speed of processing from pre- to post-training compared with 31
      participants who were randomized to the control group, F(1, 51) = 28.67, p <=
      .001, [Formula: see text] = .360. DISCUSSION: Results indicate that speed of
      processing training may improve everyday cognitive performance among older adults
      with HF. Future studies should investigate the longitudinal effects of cognitive
      training with HF patients.

PMID- 24681976
TI  - Rejuvenating clinician-scientist training.
AB  - Clinician-scientists are becoming increasingly rare in medicine as a whole, but
      especially in ophthalmology. There is a structural gap between MD-PhD training
      and K-series awards where interested candidates go through residency and
      fellowship without any structured research exposure or involvement. Furthermore,
      the success rate of the MD-PhD and K awards leaves much to be desired. The
      authors propose a redeployment of training resources to reconfigure residency and
      fellowship training programs for interested candidates with sufficient additional
      time for a credible research project, augmented salary, and sound mentoring.
      Opportunities for research training in nontraditional pathways to diversify skill
      sets and build interdisciplinary teams also would be a prime objective of this
      novel "Learn-and-Earn" approach. 

PMID- 24681978
TI  - Training the next physician scientists.

PMID- 24681977
TI  - MMPs in the neuroretina and optic nerve: modulators of glaucoma pathogenesis and
      repair?
AB  - Multiple studies in glaucoma patients and in animal models of spontaneous and
      experimentally-induced glaucoma, reported changes in the expression and activity
      of several matrix metalloproteinases (MMPs) in the retina, optic nerve, aqueous
      humor, and trabecular meshwork. These data have led to the hypothesis that MMPs
      might be involved in glaucoma onset and/or disease progression. However, reports
      are conflicting and research aiming at providing a clear definition of their
      causative role is lacking. In glaucoma, MMPs are thought to act at two different
      levels. In the trabecular meshwork, they fine-tune the aqueous humor outflow rate
      and intraocular pressure, in the neuroretina and optic nerve, however, their role
      during glaucoma disease progression is much less clear. This review provides a
      comprehensive overview of the research conducted on the expression and function
      of MMPs in the retina and optic nerve, and on the elucidation of their potential
      involvement during glaucoma pathogenesis. Additionally, we describe the insecure
      balance between detrimental and potential beneficial MMP activities during
      central nervous system recovery and how MMP-based therapies could help to
      overcome the current pitfalls in the development of retinal ganglion cell
      neuroprotection and axon regeneration approaches for the treatment of glaucoma. 

PMID- 24681979
TI  - One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4
      oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines.
AB  - A series of N-benzyl-1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2
      yl)methanamines were synthesized via one-pot reaction of appropriate benzylamine,
      pyrrole-2-carbaldehyde, (N-isocyanimino)triphenylphosphorane, and a carboxylic
      acid. The anti-tumor potential of title compounds was tested against several
      cancer cell lines by using MTT assay. Some tested compounds including 5e, 5p and
      5q exhibited comparable or better cytotoxic activity against A549, HT29 or HT1080
      cells in comparison to the reference drug doxorubicin. Also, the cytotoxic
      activity of compounds 5d and 5n against MCF-7 was better than that of
      doxorubicin. Compound 5n with IC50 value of 4.3 MUM was 4-fold more potent than
      doxorubicin. The structure-activity relationship study revealed that the
      introduction of halogen atoms on both 5-phenyl ring and N-benzyl part improved
      the cytotoxic activity against all tested cell lines. 

PMID- 24681980
TI  - Fluorinated benzophenone derivatives: balanced multipotent agents for Alzheimer's
      disease.
AB  - In an effort to develop multipotent agents against beta-secretase (BACE-1) and
      acetylcholinesterase (AChE), able to counteract intracellular ROS formation as
      well, the structure of the fluorinated benzophenone 3 served as starting point
      for the synthesis of a small library of 3-fluoro-4-hydroxy- analogues. Among the
      series, derivatives 5 and 12, carrying chemically different amino functions,
      showed a balanced micromolar potency against the selected targets. In particular,
      compound 12, completely devoid of toxic effects, seems to be a promising lead for
      obtaining effective anti-AD drug candidates. 

PMID- 24681981
TI  - Synthesis, crystal structure and biological evaluation of some novel 1,2,4
      triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines.
AB  - Nitrogen-containing heterocycles are of particular interest and significant
      importance for the discovery of potent bioactive agents in pharmaceutical
      industry. The present study reports the synthesis of a library of new conjugated
      heterocycles including 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4
      thiadiazoles (4a-g and 5a-e) and 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4
      thiadiazines (6a-h), by cyclocondensation reaction of 4-amino-5-(pyridin-4-yl)-4H
      1,2,4-triazole-3-thiol 3 with various substituted aromatic acids and phenacyl
      bromides, respectively. The structures of newly synthesized compounds were
      characterized by elemental analysis, IR, (1)H and (13)C NMR spectroscopy and in
      case of 4c by X-ray crystallographic analysis. Newly synthesized
      triazolothiadiazoles and thiadiazines were screened for acetyl- and butyryl
      cholinesterases and alkaline phosphatase inhibition. Almost all of the compounds
      showed good to excellent activities against acetylcholinesterase more than the
      reference drugs. Compound 5d exhibited IC50 value 0.77 +/- 0.08 MUM against
      acetylcholinesterase and 4a showed IC50 9.57 +/- 1.42 MUM against
      butyrylcholinesterase. Among all the tested compounds, 4a also proved as
      excellent inhibitor of alkaline phosphatase with IC50 0.92 +/- 0.03 MUM. These
      heteroaromatic hybrid structures were also tested for their anticancer activity
      against lung carcinoma (H157) and kidney fibroblast (BHK-21) cell lines and
      leishmanias. Variable cell growth inhibitory activities were obtained and many
      compounds exhibit potent %inhibition. 

PMID- 24681982
TI  - Discovery of azaisoerianin derivatives as potential antitumors agents.
AB  - A series of N-methyl-diarylamines 2 was designed and synthesized as a novel class
      of CA-4 and isoCA-4 analogues. Compounds 2b and 2m showed excellent
      antiproliferative activity with mean GI50 values at a nanomolar level in a
      diverse set of human cancer cells. These compounds also inhibited tubulin
      assembly at a micromolar range, arrested the cellular cycle in the G2/M phase and
      induced apoptosis at very low concentrations. Preliminary in vitro results
      revealed that 2b and 2m displayed substantial efficacy as potent antivascular
      agents. Docking studies indicates that these lead compounds showed a binding mode
      similar to those observed with isoCA-4 at the colchicine binding site of tubulin.

PMID- 24681983
TI  - 11a-N-Tosyl-5-deoxi-pterocarpan (LQB-223), a promising prototype for targeting
      MDR leukemia cell lines.
AB  - Aza-deoxi-pterocarpans (1) were synthesized through palladium-catalyzed aza
      arylation of dihydronaphtalen, and showed antineoplastic effect on MDR leukemic
      cell lines (K562, Lucena-1 and FEPS). Compounds 1c-d were prepared to identify
      the pharmacophoric group responsible for the activity as well as compounds 2a-c
      were prepared to evaluate the structural requirements in the D-ring. LQB-223 (1b)
      is the most promising antileukemic agent since it was the most active on MDR
      cells without detectable toxicity to normal immune system cells. 

PMID- 24681984
TI  - One-pot synthesis and radical scavenging activity of novel polyhydroxylated 3
      arylcoumarins.
AB  - An unexpected domino rearrangement brought about the development of a novel one
      pot procedure for synthesis of coumarins. This protocol allowed the gram-scale
      synthesis of a variety of polyhydroxylated derivatives 3a-p, from readily
      available starting materials at a low cost. Based on two proven intermediates, a
      probable mechanism consisting of boron tribromide induced demethylation/lactone
      ring opening/elimination/isomerization/lactone ring closure reaction sequence of
      in situ formed 3-aryl-3,4-dihydroisocoumarin-4-carboxylic acids was deduced.
      Compared to the common methods, used for the synthesis of coumarins, the proposed
      herein possesses great advantages, such as mild conditions, good yields for short
      reaction time, simple work-up procedure and easy isolation of the final products.
      The structure of the newly synthesized compounds 3a-p was established by
      spectroscopic methods ((1)H NMR, (13)C NMR, IR, MS and HRMS) and their radical
      scavenging activity was evaluated in vitro against 1,1-diphenyl-2-picrylhydrazyl
      free radical (DPPH). The results obtained show that compounds 3g-p posses higher
      radical scavenging activity (3.16 <= SC50 [MUM] <= 6.82) than well-known
      antioxidants such as trolox, protocatechuic acid, caffeic acid and gallic acid
      (SC50 [MUM] = 9.34, 8.83, 9.48, 5.33, respectively), which is a precondition for
      promising antioxidant activity of these compounds to be expected. 

PMID- 24681985
TI  - Synthesis, characterization and pharmacological screening of some novel 5
      imidazopyrazole incorporated polyhydroquinoline derivatives.
AB  - A new category of polyhydroquinoline derivatives 8a-t were synthesized in
      moderate to good yield (64-85%) by one-pot three-component cyclocondensation
      reaction of 5-(1H-imidazol-1-yl)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde 3
      with various enaminones 6a-h and different active methylene compounds
      (malononitrile 7a, ethylcaynoacetate 7b and caynoacetamide 7c) in absolute
      ethanol. The newly synthesized compounds were evaluated for their in vitro
      antimalarial activity against Plasmodium falciparum, in vitro antibacterial
      activity against a panel of pathogenic strains of bacteria and fungi and also for
      their antitubercular activity against Mycobacterium tuberculosis H37Rv strain.
      Two of them (8n, 8t) exhibited excellent antimalarial activity. Some of them
      exhibited excellent antibacterial activity and moderate antituberculosis activity
      compared with the first line drugs. 

PMID- 24681987
TI  - Cytotoxic properties of D-gluco-, D-galacto- and D-manno-configured 2-amino-2
      deoxy-glycerolipids against epithelial cancer cell lines and BT-474 breast cancer
      stem cells.
AB  - Glycosylated antitumor ether lipids (GAELs) 6 and 7 containing a alpha- or beta-D
      gluco-configured 2-amino-2-deoxy (2-NH2-Glc) sugar moiety linked to a
      glycerolipid aglycone kill cancer cell lines via a non-apoptotic mechanism that
      could be exploited to kill cancer stem cells. To test this hypothesis and develop
      novel potent GAEL analogs, we synthesized GAELS which contain D-galacto- and D
      manno-configured 2-amino-2-deoxy sugar moieties (2-NH2-Gal or 2-NH2-Man) and
      investigated their cytotoxicity against human epithelial cancer cell lines and
      cancer stem cells derived from BT-474 breast cancer cells. Within the class of D
      galacto-configured GAELs, we prepared both O- and S-glycosidic linkages as well
      as their corresponding alpha- and beta-anomers and screened against breast (BT
      474, JIMT-1 and BT-549), pancreas (MiaPaCa2) and prostate cancer (DU145, PC3)
      cancer cell lines. The alpha-anomeric 2-NH2-Gal-based lipid 1 was the most active
      of all the compounds tested with CC50 values of 4.4-8 MUM and is the most active
      GAEL synthesized to date. The beta-anomer 2 was 4->5-fold less active than 1.
      Replacement of the alpha-O-glycosidic by an alpha-S-glycosidic linkage resulted
      in a 2-4-fold reduction in activity, while the beta-S-glycolipid 4 was inactive.
      In comparison, alpha-configured 2-NH2-Man-based glycerolipid 5 displayed very
      little activity with CC50 > 30 MUM. The effect of the most active GAELs, 1, 6, or
      7, on cancer stem cell viability revealed that all three inhibited the formation
      of tumorspheres from BT-474 cancer stem cell lines, caused the disintegration of
      preformed tumorspheres and resulted in total loss of cell viability of the cancer
      stem cells at concentrations of 20 MUM. In contrast, the related antitumor ether
      lipid gold standard, edelfosine that is in clinical development was much less
      effective in preventing tumorsphere formation and affecting the viability of the
      cancer stem cells. Taken together our study demonstrates that alpha-GAEL anomers
      are more potent than their corresponding beta-anomers and that the nature of the
      CHO moiety as well as the glycosidic bond significantly affects activity. The
      study also showed that GAELs are effective in killing CSCs while the apoptosis
      inducing edelfosine is not.

PMID- 24681986
TI  - Synthesis and kinase inhibitory activity of new sulfonamide derivatives of
      pyrazolo[4,3-e][1,2,4]triazines.
AB  - A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine has
      been synthesized and characterized. Their anticancer activity was tested in vitro
      against multiple human cancer cell lines and were found to have dose-dependent
      antiproliferative effects. Furthermore, some of the new compounds inhibited the
      Abl protein kinase with low micromolar IC50 values and exhibited selective
      activity against the Bcr-Abl positive K562 and BV173 cell lines, providing
      starting points for the further development of this new kinase inhibitor
      scaffold. 

PMID- 24681988
TI  - Novel binding regioselectivity in the interpenetration of a non-symmetric axle
      into a non-symmetric pillar[5]arene wheel.
AB  - We describe the regioselective complexation of a non-symmetric 5
      bromovaleronitrile axle by a non-symmetric pillar[5]arene bearing different alkyl
      (methyl and pentyl) rims, forming an oriented interpenetrated complex with the
      directionality of CN@methyl rim and Br@pentyl rim. 

PMID- 24681991
TI  - [Comparison of intestinal bacteria composition identified by various analytical
      methods].
AB  - Many different kinds of bacteria are normally found in the intestines of healthy
      humans and animals. To study the ecology and function of these intestinal
      bacteria, the culture method was fundamental until recent years, and suitable
      agar plates such as non-selective agar plates and several selective agar plates
      have been developed. Furthermore, the roll-tube, glove box, and plate-in-bottle
      methods have also been developed for the cultivation of fastidious anaerobes that
      predominantly colonize the intestine. Until recently, the evaluation of
      functional foods such as pre- and probiotics was mainly done using culture
      methods, and many valuable data were produced. On the other hand, genomic
      analysis such as the fluorescence in situ hybridization (FISH), quantitative PCR
      (qPCR), clone-library, denaturing gradient gel electrophoresis (DGGE),
      temperature gradient gel electrophoresis (TGGE), terminal-restriction fragment
      length polymorphism (T-RFLP) methods, and metagenome analysis have been used for
      the investigation of intestinal microbiota in recent years. The identification of
      bacteria is done by investigation of the phenotypic characteristics in culture
      methods, while rRNA genes are used as targets in genomic analysis. Here, I
      compare the fecal bacteria identified by various analytical methods. 

PMID- 24681990
TI  - [Little animals observed by Antony van Leeuwenhoek].
AB  - Antony van Leeuwenhoek is the discoverer of bacteria and other microorganisms.
      However, his name is currently not as well-known as those of Louis Pasteur,
      Robert Koch or Shibasaburo Kitasato. Why not? To answer this question I read a
      book published in 1932 by Clifford Dobell, an English protozoologist, and found
      some answers. First, Leeuwenhoek was not a professional scientist in any
      university or scientific institute, but merely an average citizen in Delft,
      Holland, working as a merchant in his own shop, and later he also served as an
      office-holder in Delft city hall. Second, he made and invented his own
      microscopes but never made his work on microscopes and observation techniques
      widely known to the public. Accordingly, after his death, his excellent
      techniques for observing microorganisms were not handed down to the next
      generation and eventually became forgotten by the scientific community. Although
      he did not write any scientific paper, he did write about his observations in
      many letters addressed to the Royal Society of London. Dr. Dobell had translated
      most of them into English and included them in his book. I picked up and
      translated several of these letters into Japanese and have included them in this
      review to show how he described his observations and also what he thought about
      the presence of such small animals invisible to the naked eye. By reading this
      review I hope you will come to understand the efforts and abilities of a citizen
      in Delft about 340 years ago. 

PMID- 24681992
TI  - [Bacterial infections, what we can learn from each outbreak].
AB  - Studies on outbreaks or incidences of infectious diseases and food poisonings are
      the starting points in research. Analyses of the outbreaks will provide the
      mechanism by which the illnesses occur and the establishment of countermeasure.
      We report here some sensational outbreaks which recently occurred in Japan: 1)
      enterohemorrhagic Escherichia coli (EHEC) O157 outbreaks by pickled Chinese
      cabbage in Hokkaido, 2) EHEC O157/O111 outbreaks by raw beef in Toyama
      Prefecture, 3) parasitic food poisoning due to raw olive flounder consumption in
      the western Japan, and 4) botulism due to the consumption of vacuum packed food
      in Tottori Prefecture. 

PMID- 24681995
TI  - From local to global: CDPKs in systemic defense signaling upon microbial and
      herbivore attack.
AB  - Calcium-dependent protein kinases (CDPKs) are multifunctional proteins in which a
      calmodulin-like calcium-sensor and a protein kinase effector domain are combined
      in one molecule. Not surprisingly, CDPKs were primarily recognized as signaling
      mediators, which perceive rapid intracellular changes of Ca(2+) ion
      concentration, for example triggered by environmental stress cues, and relay them
      into specific phosphorylation events to induce further downstream stress
      responses. In the context of both, plant exposure to biotrophic pathogens-derived
      signals as well as plant attack by herbivores and wounding, CDPKs were shown to
      undergo rapid biochemical activation within seconds to minutes after stimulation
      and to induce local defence-responses including respective changes in gene
      expression patterns. In addition, CDPK function was correlated with the control
      of either salicylic acid-mediated or jasmonic acid-mediated phytohormone
      signaling pathways, mediating long term resistance to either biotrophic bacterial
      pathogens or herbivores also in distal parts of a plant. It has long been unclear
      how an individual enzyme can affect both rapid local as well as long-term distal
      immune responses. Here, we discuss recently raised topics from the field of CDPK
      research, in particular with a view on the identification of in vivo
      phosphorylation targets, which provide first mechanistic insights into the dual
      role of these enzymes: On the one hand as component of a self-activating circuit
      responsible for rapid plasma-membrane anchored cell-to-cell signal propagation
      from local to distal plant sites. On the other hand as nuclear-located regulators
      of transcription factor activity. Finally, we will highlight the dual function of
      calcium sensors in plasma-membrane/calcium-mediated signal propagation and in
      phytohormone signaling-dependent systemic resistance in immune responses to both,
      bacterial pathogens and herbivores. 

PMID- 24681996
TI  - Association between HACEK bacteraemia and endocarditis.
AB  - We retrospectively examined medical records of 87 patients with bacteraemia
      caused by members of the HACEK group (Haemophilus parainfluenzae, Aggregatibacter
      actinomycetemcomitans, Aggregatibacter aphrophilus, Aggregatibacter
      paraphrophilus, Cardiobacterium spp., Eikenella corrodens and Kingella spp.) to
      determine whether endocarditis was present, as defined by the Duke criteria. The
      overall positive predictive value (PPV) of HACEK bacteraemia for endocarditis was
      60 %. The PPV varied with different HACEK species from 0 % (E. corrodens) to 100
      % (A. actinomycetemcomitans).

PMID- 24681993
TI  - HLA alleles association with changes in bone mineral density in HIV-1-infected
      adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.
AB  - BACKGROUND: There are limited data regarding the influence of human leukocyte
      antigen (HLA) polymorphisms on reduced bone mineral density (BMD). We
      investigated the relationship between HLA supertypes and BMD in HIV-infected
      adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC) or
      abacavir-lamivudine (ABC-3TC) in the STEAL study. METHODS: Lumbar spine and right
      hip BMD were measured by Dual-energy X-ray absorptiometry (DXA). HLA genotypes at
      the 2-digit level were classified into class I and II supertypes. Student's t
      tests were used to test the association between HLA supertypes and changes in hip
      and spine BMD over 96 weeks for the whole cohort and stratified by randomised
      groups. The relationship between HLA supertypes and BMD was also assessed in the
      subgroup of participants that were naive to both ABC and TDF at study entry.
      RESULTS: Class II supertypes were mainly associated with hip BMD change. Overall,
      compared to participants not carrying HLA-DQ3, participants expressing DQ3 had
      less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. -0.006
      g/cm2, 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. -0.006 g/cm2, 95%CI
      0.001 to 0.023, p = 0.041). In participants that were naive to both ABC and TDF
      at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less
      bone loss compared with those not carrying DQ3 (hip: 0.001 vs. -0.032 g/cm2; diff
      0.033; 95%CI 0.017 to 0.049; p<0.001; spine: 0.007 vs. -0.023 g/cm2; diff 0.035;
      95%CI 0.014 to 0.056; p = 0.001). CONCLUSIONS: In this cohort of HIV-infected
      adults, there was an association between bone status and HLA supertypes,
      particularly HLA-DQ3. TRIAL REGISTRATION: Clinicaltrials.gov NCT00192634.

PMID- 24681998
TI  - Parkinson's disease: a brief review.

PMID- 24681999
TI  - Honoring the Medicine: searching for the embodiment of spiritual commitment and
      philosophy for student physicians.
AB  - Honoring the Medicine is a project that grew from an assignment that I created
      for an online course I developed entitled "Introduction to Spirituality and
      Medicine." In an effort to create a consciousness that would explore the sacred
      oaths of the practice of medicine, I asked medical students who took the course
      to write their own sacred oath of healing that they would carry into their
      practice of medicine. Participants were asked to read the Hippocratic Oath and
      the Osteopathic Oath and to reflect on the ethical and humanistic aspects of
      each. Participants identified various areas of importance including the
      integration of mind, body and soul, empathy, compassion, and respect. Every
      participant identified their own attributes of healing. This exemplifies how 1
      community--the medical community--can search deeper inside themselves to create a
      sacred model for humanistic medicine. This model is one that identifies
      attributes that all communities can practice in their lives, for the humanistic
      model touches every community and every community member.

PMID- 24681994
TI  - Association of glycogen synthase kinase-3beta with Parkinson's disease (review).
AB  - Glycogen synthase kinase-3 (GSK-3) is a pleiotropic serine/threonine protein
      kinase found in almost all eukaryotes. It is structurally highly conserved and
      has been identified as a multifaceted enzyme affecting a wide range of biological
      functions, including gene expression and cellular processes. There are two
      closely related isoforms of GSK-3; GSK-3alpha and GSK-3beta. The latter appears
      to play crucial roles in regulating the pathogenesis of diverse diseases,
      including neurodegenerative disease. The present review focuses on the
      involvement of this protein in Parkinson's disease (PD), a common
      neurodegenerative disorder characterized by the gradually progressive and
      selective loss of dopaminergic neurons, and by intracellular inclusions known as
      Lewy bodies (LBs) expressed in surviving neurons of the substantia nigra (SN).
      GSK-3beta is involved in multiple signaling pathways and has several
      phosphorylation targets. Numerous apoptotic conditions can be facilitated by the
      GSK-3beta signaling pathways. Studies have shown that GSK-3beta inhibition
      protects the dopaminergic neurons from various stress-induced injuries,
      indicating the involvement of GSK-3beta in PD pathogenesis. However, the
      underlying mechanisms of the protective effect of GSK-3beta inhibition on
      dopaminergic neurons in PD is not completely understood. Multiple pathological
      events have been recognized to be responsible for the loss of dopaminergic
      neurons in PD, including mitochondrial dysfunction, oxidative stress, protein
      aggregation and neuroinflammation. The present review stresses the regulatory
      roles of GSK-3beta in these events and in dopaminergic neuron degeneration, in an
      attempt to gain an improved understanding of the underlying mechanisms and to
      provide a potential effective therapeutic target for PD.

PMID- 24681997
TI  - Microfluidic immunocapture of circulating pancreatic cells using parallel EpCAM
      and MUC1 capture: characterization, optimization and downstream analysis.
AB  - We have developed and optimized a microfluidic device platform for the capture
      and analysis of circulating pancreatic cells (CPCs) and pancreatic circulating
      tumor cells (CTCs). Our platform uses parallel anti-EpCAM and cancer-specific
      mucin 1 (MUC1) immunocapture in a silicon microdevice. Using a combination of
      anti-EpCAM and anti-MUC1 capture in a single device, we are able to achieve
      efficient capture while extending immunocapture beyond single marker recognition.
      We also have detected a known oncogenic KRAS mutation in cells spiked in whole
      blood using immunocapture, RNA extraction, RT-PCR and Sanger sequencing. To allow
      for downstream single-cell genetic analysis, intact nuclei were released from
      captured cells by using targeted membrane lysis. We have developed a staining
      protocol for clinical samples, including standard CTC markers; DAPI, cytokeratin
      (CK) and CD45, and a novel marker of carcinogenesis in CPCs, mucin 4 (MUC4). We
      have also demonstrated a semi-automated approach to image analysis and CPC
      identification, suitable for clinical hypothesis generation. Initial results from
      immunocapture of a clinical pancreatic cancer patient sample show that parallel
      capture may capture more of the heterogeneity of the CPC population. With this
      platform, we aim to develop a diagnostic biomarker for early pancreatic
      carcinogenesis and patient risk stratification. 

PMID- 24682000
TI  - An open-label study to elucidate the effects of standardized Bacopa monnieri
      extract in the management of symptoms of attention-deficit hyperactivity disorder
      in children.
AB  - CONTEXT: Attention-deficit hyperactivity disorder (ADHD) is a clinically
      heterogeneous disorder of inattention, hyperactivity, and impulsivity or
      difficulty in controlling behavior. Psychostimulant medications remain the
      mainline treatment for children with ADHD; however, the average response rate to
      these medications is 70%, and up to 30% of children do not respond to these
      medications or are unable to tolerate such potential adverse effects as nausea,
      insomnia, and weight loss. OBJECTIVE: The study investigated the effectiveness of
      standardized Bacopa monnieri extract (SBME) in ameliorating the severity of the
      symptoms of ADHD in children. DESIGN: The clinical trial was conducted as an open
      label study. SETTING: The study was conducted at the Center for Research in
      Mental Retardation (CREMERE) in Mumbai, India, from 2008 to 2010. PARTICIPANTS:
      Thirty-one children were participants in the trial. They were 6-12 y of age, with
      an age of onset of ADHD before 7 y of age, as defined by the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-IV) criteria for ADHD. INTERVENTION:
      The children received SBME at a dose of 225 mg/d for a period of 6 mo. The
      specific SBME used in the study was BacoMind (M/s Natural Remedies, Bangalore,
      India). OUTCOME MEASURES: Subsequent to the screening of participants, the
      research team administered the Parent Rating Scale to assess the ADHD symptom
      scores at baseline, and the team administered it again at the end of the 6 mo of
      treatment. RESULTS: SBME significantly reduced the subtests scores of ADHD
      symptoms, except for social problems. The symptom scores for restlessness were
      reduced in 93% of children, whereas improvement in self-control was observed in
      89% of the children. The attention-deficit symptoms were reduced in 85% of
      children. Similarly, symptom scores for learning problems, impulsivity, and
      psychiatric problems were reduced for 78%, 67%, and 52% of children,
      respectively. It was observed that 74% of the children exhibited up to a 20%
      reduction, while 26% of children showed between a 21% and a 50% reduction in the
      total subtests scores. CONCLUSION: Standardized extract of B monnieri was found
      to be effective in alleviating the symptoms of ADHD and was well-tolerated by the
      children.

PMID- 24682001
TI  - The effect of humor on short-term memory in older adults: a new component for
      whole-person wellness.
AB  - CONTEXT: For older adults, the damaging effects of aging and stress can impair
      the ability to learn and sustain memory. Humor, with its associated mirthful
      laughter, can reduce stress and cortisol, a stress hormone. Chronic release of
      cortisol can damage hippocampus neurons, leading to impairment of learning and
      memory. OBJECTIVES: The primary goal of this study was to determine whether
      watching a humorous video had an effect on short-term memory in an older
      population. DESIGN: The research team designed a randomized, controlled trial.
      SETTING: The study took place at Loma Linda University in Loma Linda, California.
      PARTICIPANTS: The research team recruited 20 normal, healthy, older adults, 11
      males and 9 females. INTERVENTION: The humor group (n = 10, mean = 69.3 +/- 3.7
      y) self-selected 1 of 2 humorous videos--a Red Skelton comedy or a montage of
      America's Funniest Home Videos--and watched it for 20 min. A control group (n =
      10, mean = 68.7 +/- 5.5 y) sat calmly for 20 min and were not allowed to read,
      sleep, or talk on a cell phone. OUTCOME MEASURES: The Rey Auditory Verbal
      Learning Test was used to assess short-term memory--learning ability, delayed
      recall, and visual recognition. Salivary cortisol levels were measured at
      predetermined times. RESULTS: Learning ability improved by 38.5% and 24.0% in the
      humor and control groups, respectively (P = .014). Delayed recall improved by
      43.6% and 20.3% in the humor and control groups, respectively (P =.029). Within
      the humor group, delayed recall (43.6%) was significant compared with learning
      ability (38.5%) (P = .002). At 3 predetermined time points, significant decreases
      in salivary cortisol were observed in the humor group (P = .047, P = .046, and P
      = .062, respectively). CONCLUSION: The study's findings suggest that humor can
      have clinical benefits and rehabilitative implications and can be implemented in
      programs that support whole-person wellness for older adults. Learning ability
      and delayed recall are important to these individuals for a better quality of
      life--considering mind, body, spirit, social, and economic aspects. Older adults
      may have age-associated memory deficiencies. However, medical practitioners now
      can offer positive, enjoyable, and beneficial humor therapies to improve these
      deficiencies.

PMID- 24682002
TI  - William Walsh, PhD: epigenetics as a source of mental health dysfunction and the
      nutrient-based solution.

PMID- 24682003
TI  - The impact of stimulus valence and emotion regulation on sustained brain
      activation: task-rest switching in emotion.
AB  - Task-rest interactions, defined as the modulation of brain activation during
      fixation periods depending on the preceding stimulation and experimental
      manipulation, have been described repeatedly for different cognitively demanding
      tasks in various regions across the brain. However, task-rest interactions in
      emotive paradigms have received considerably less attention. In this study, we
      therefore investigated task-rest interactions evoked by the induction and
      instructed regulation of negative emotion. Whole-brain, functional MRI data were
      acquired from 55 healthy participants. Two-level general linear model statistics
      were computed to test for differences between conditions, separately for
      stimulation and for fixation periods, as well as for interactions between
      stimulation and fixation (task-rest interactions). Results showed that the
      regulation of negative emotion led to reverse task-rest interactions (decreased
      activation during stimulation but increased activation during fixation) in the
      amygdala as well as in visual cortex regions and to concordant task-rest
      interactions (increased activation during both, stimulation and fixation) in the
      dorsolateral prefrontal cortex as well as in a number of brain regions at the
      intersection of the default mode and the dorsal attention networks. Thus, this
      first whole-brain investigation of task-rest interactions following the induction
      and regulation of negative emotion identified a widespread specific modulation of
      brain activation in regions subserving emotion generation and regulation as well
      as regions implicated in attention and default mode. 

PMID- 24682004
TI  - Transforming growth factor-beta signaling network regulates plasticity and
      lineage commitment of lung cancer cells.
AB  - Identification of target cells in lung tumorigenesis and characterization of the
      signals that control their behavior is an important step toward improving early
      cancer diagnosis and predicting tumor behavior. We identified a population of
      cells in the adult lung that bear the EpCAM+CD104+CD49f+CD44+CD24loSCA1+
      phenotype and can be clonally expanded in culture, consistent with the properties
      of early progenitor cells. We show that these cells, rather than being restricted
      to one tumor type, can give rise to several different types of cancer, including
      adenocarcinoma and squamous cell carcinoma. We further demonstrate that these
      cells can be converted from one cancer type to the other, and this plasticity is
      determined by their responsiveness to transforming growth factor (TGF)-beta
      signaling. Our data establish a mechanistic link between TGF-beta signaling and
      SOX2 expression, and identify the TGF-beta/SMAD/SOX2 signaling network as a key
      regulator of lineage commitment and differentiation of lung cancer cells. 

PMID- 24682006
TI  - Analysis of macular and peripapillary choroidal thickness in glaucoma patients by
      enhanced depth imaging optical coherence tomography.
AB  - BACKGROUND: To compare the macular and peripapillary choroidal thickness between
      normal and glaucoma eyes and find out factors related to choroidal thickness
      using enhanced depth imaging (EDI) of Heidelberg Spectralis SD-OCT. STUDY DESIGN:
      Cross-sectional transverse study. METHODS: A total of 108 glaucoma patients and
      48 healthy controls were included in the analysis. Choroidal thickness was
      measured from 6 mm length radial B-scans at the macular and the optic nerve head
      by EDI OCT. Choroidal thickness was compared between normal controls, normal
      tension glaucoma (NTG) patients, and primary open-angle glaucoma (POAG) patients.
      Factors related to choroidal thickness were analyzed by regression analysis.
      RESULTS: There were no differences in average, temporal, nasal, superior, and
      inferior macular choroidal thickness between normal, NTG, and POAG eyes. The
      peripapillary thickness did not differ between normal and POAG eyes; however,
      average, temporal, nasal, superior, and inferior peripapillary choroidal
      thickness were significantly thinner in NTG eyes. Axial length (beta=-11.36,
      P<0.001) was the most significant factor associated with peripapillary choroidal
      thickness, followed by age (beta=-5.10, P<0.001). Glaucoma type (beta=-11.28,
      P<0.001) were also significantly associated with peripapillary choroidal
      thickness. CONCLUSIONS: Peripapillary choroidal thickness was significantly
      reduced in NTG eyes based on EDI OCT measurements in vivo.

PMID- 24682005
TI  - Decreased mitochondrial priming determines chemoresistance of colon cancer stem
      cells.
AB  - Tumor heterogeneity is in part determined by the existence of cancer stem cells
      (CSCs) and more differentiated tumor cells. CSCs are considered to be the
      tumorigenic root of cancers and suggested to be chemotherapy resistant. Here we
      exploited an assay that allowed us to measure chemotherapy-induced cell death in
      CSCs and differentiated tumor cells simultaneously. This confirmed that CSCs are
      selectively resistant to conventional chemotherapy, which we revealed is
      determined by decreased mitochondrial priming. In agreement, lowering the anti
      apoptotic threshold using ABT-737 and WEHI-539 was sufficient to enhance
      chemotherapy efficacy, whereas ABT-199 failed to sensitize CSCs. Our data
      therefore point to a crucial role of BCLXL in protecting CSCs from chemotherapy
      and suggest that BH3 mimetics, in combination with chemotherapy, can be an
      efficient way to target chemotherapy-resistant CSCs. 

PMID- 24682007
TI  - Royal jelly-like protein localization reveals differences in hypopharyngeal
      glands buildup and conserved expression pattern in brains of bumblebees and
      honeybees.
AB  - Royal jelly proteins (MRJPs) of the honeybee bear several open questions. One of
      them is their expression in tissues other than the hypopharyngeal glands (HGs),
      the site of royal jelly production. The sole MRJP-like gene of the bumblebee,
      Bombus terrestris (BtRJPL), represents a pre-diversification stage of the MRJP
      gene evolution in bees. Here we investigate the expression of BtRJPL in the HGs
      and the brain of bumblebees. Comparison of the HGs of bumblebees and honeybees
      revealed striking differences in their morphology with respect to sex- and caste
      specific appearance, number of cells per acinus, and filamentous actin (F-actin)
      rings. At the cellular level, we found a temporary F-actin-covered meshwork in
      the secretory cells, which suggests a role for actin in the biogenesis of the end
      apparatus in HGs. Using immunohistochemical localization, we show that BtRJPL is
      expressed in the bumblebee brain, predominantly in the Kenyon cells of the
      mushroom bodies, the site of sensory integration in insects, and in the optic
      lobes. Our data suggest that a dual gland-brain function preceded the
      multiplication of MRJPs in the honeybee lineage. In the course of the honeybee
      evolution, HGs dramatically changed their morphology in order to serve a food
      producing function. 

PMID- 24682008
TI  - Interaction among Saccharomyces cerevisiae pheromone receptors during
      endocytosis.
AB  - This study investigates endocytosis of Saccharomyces cerevisiae alpha-factor
      receptor and the role that receptor oligomerization plays in this process. alpha
      factor receptor contains signal sequences in the cytoplasmic C-terminal domain
      that are essential for ligand-mediated endocytosis. In an endocytosis
      complementation assay, we found that oligomeric complexes of the receptor undergo
      ligand-mediated endocytosis when the alpha-factor binding site and the
      endocytosis signal sequences are located in different receptors. Both in vitro
      and in vivo assays suggested that ligand-induced conformational changes in one
      Ste2 subunit do not affect neighboring subunits. Therefore, recognition of the
      endocytosis signal sequence and recognition of the ligand-induced conformational
      change are likely to be two independent events. 

PMID- 24682009
TI  - Properties of a non-bioactive fluorescent derivative of differentiation-inducing
      factor-3, an anti-tumor agent found in Dictyostelium discoideum.
AB  - Differentiation-inducing factor-3 (DIF-3), found in the cellular slime mold
      Dictyostelium discoideum, and its derivatives, such as butoxy-DIF-3 (Bu-DIF-3),
      are potent anti-tumor agents. To investigate the activity of DIF-like molecules
      in tumor cells, we recently synthesized a green fluorescent DIF-3 derivative,
      BODIPY-DIF-3G, and analyzed its bioactivity and cellular localization. In this
      study, we synthesized a red (orange) fluorescent DIF-3 derivative, BODIPY-DIF-3R,
      and compared the cellular localization and bioactivities of the two BODIPY-DIF-3s
      in HeLa human cervical cancer cells. Both fluorescent compounds penetrated the
      extracellular membrane within 0.5&emsp14;h and localized mainly to the
      mitochondria. In formalin-fixed cells, the two BODIPY-DIF-3s also localized to
      the mitochondria, indicating that the BODIPY-DIF-3s were incorporated into
      mitochondria independently of the mitochondrial membrane potential. After
      treatment for 3 days, BODIPY-DIF-3G, but not BODIPY-DIF-3R, induced mitochondrial
      swelling and suppressed cell proliferation. Interestingly, the swollen
      mitochondria were stainable with BODIPY-DIF-3G but not with BODIPY-DIF-3R. When
      added to isolated mitochondria in vitro, BODIPY-DIF-3G increased dose-dependently
      the rate of O2 consumption, but BODIPY-DIF-3R did not. These results suggest that
      the bioactive BODIPY-DIF-3G suppresses cell proliferation, at least in part, by
      altering mitochondrial activity, whereas the non-bioactive BODIPY-DIF-3R
      localizes to the mitochondria but does not affect mitochondrial activity or cell
      proliferation. 

PMID- 24682010
TI  - Selection of valves for TAVR: is the CHOICE clear?

PMID- 24682011
TI  - Sediment particle size and initial radiocesium accumulation in ponds following
      the Fukushima DNPP accident.
AB  - This study used particle size analysis to investigate the initial accumulation
      and trap efficiency of radiocesium ((137)Cs) in four irrigation ponds, ~4-5
      months after the Fukushima Dai-ichi nuclear power plant (DNPP) accident. Trap
      efficiency, represented by the inventory of (137)Cs in pond sediment to the
      inventory of radiocesium in soil surrounding the pond (i.e., total (137)Cs
      inventory), was less than 100% for all but one pond. Trap efficiency decreased as
      sediment particle size increased, indicating that sediments with a smaller
      particle size accumulate more (137)Cs. In ponds showing low trap efficiency, fine
      sediment containing high concentrations of (137)Cs appeared to be removed from
      the system by hydraulic flushing, leaving behind mostly coarse sediment. The
      results of this study suggest that sediment particle size can be used to estimate
      the initial accumulation and trap efficiency of (137)Cs in pond sediment, as well
      as the amount lost through hydraulic flushing. 

PMID- 24682012
TI  - Estimation of the respiratory tract burden resulting from a prolonged inhalation
      exposure to aerosols of DU, based on the U in a 24-h urine sample taken years
      after exposure.
AB  - A procedure is presented to estimate the respiratory tract burden from a
      prolonged inhalation exposure to particulate matter of depleted uranium, in cases
      where the rate of deposition is an unknown function. The precise range of
      possible values is identified. The calculations are based on the amount of
      depleted uranium measured in a single 24-h urine sample. In order to present an
      example, a simplified pharmacokinetical model is introduced. The results
      presented in this article are valid for any pharmacokinetical model represented
      by homogeneous linear differential equations with constant coefficients and non
      zero initial values, and that clearly includes the International Commission on
      Radiological Protection model. In fact, they are applicable to any monitorable
      quantity measured over a short period of time, a monitorable quantity with a
      kinetic that can be described using a structurally similar system of differential
      equations to one describing these pharmacokinetical models. 

PMID- 24682013
TI  - Pharmacokinetics and liver distribution study of unbound curdione and curcumol in
      rats by microdialysis coupled with rapid resolution liquid chromatography (RRLC)
      and tandem mass spectrometry.
AB  - A sensitive, specific, convenient and endogenous interference-free microdialysis
      sampling method coupled with RRLC-MS was successfully developed and applied to
      the determination of protein-unbound curdione and curcumol in biological samples.
      Microdialysis probes were simultaneously inserted into the jugular vein toward
      heart and the median lobe near the center of liver of rats under anesthesia. The
      separation was accomplished on a Zorbax SB-C18 column (2.1 mm * 50 mm, 1.8 MUm)
      with a gradient elution and chromatography was conducted with RRLC system.
      Analytes were detected by positive ion electrospray tandem mass spectrometry and
      quantified on the basis of extracted ion chromatography (EIC) peak area signal.
      The calibration curves were linear over the range of 3.3-213.2 ng/mL for curdione
      and 8.1-519.2 ng/mL for curcumol. All the validation data, such as accuracy,
      precision, stability and matrix effect were satisfactory and within the required
      limits. The validated method was successfully applied to the pharmacokinetic
      study of curdione and curcumol in rat blood and liver after oral administration
      of Rhizoma Curcumae extracts. The results could provide a meaningful basis for
      better understanding of the intracorporal process of Rhizoma Curcumae, which
      would be helpful for further study both in clinic and laboratory.

PMID- 24682014
TI  - Optical biosensor analysis in studying new synthesized bicalutamide analogs
      binding to androgen receptor.
AB  - Bicalutamide (Casodex(r)) is a non-steroidal anti-androgen drug used in the
      treatment of prostate cancer, which represents the second most common malignancy
      diagnosed in men worldwide. In this work, we analyze the ability of some novel
      bicalutamide analogs to bind the androgen receptor, by using an optical
      biosensor. Androgen receptor was covalently immobilized on a carboxy methyl
      dextran matrix. The immobilized receptor chip was then used for the binding
      experiments of the bicalutamide analogs. The (R)-bicalutamide dissociation
      constant was in good agreement to the value reported in literature obtained by
      using radiolabeled targets. Most of the new synthesized compounds showed higher
      androgen receptor binding level, when compared to the reference. Our results
      clearly indicate that the surface plasmon resonance (SPR) technique offers many
      advantages with respect to other available technologies in terms of studying
      biomolecular interactions. Moreover, this study provides an effective methodology
      for determining the binding affinity of novel chemical entities for the isolated
      androgen receptor, thus excluding possible off-target interactions occurring in
      conventional cell-based techniques.

PMID- 24682015
TI  - A novel UPLC/MS/MS method for rapid determination of metapristone in rat plasma,
      a new cancer metastasis chemopreventive agent derived from mifepristone (RU486).
AB  - Mifepristone (RU486) is a chemical abortifacient used by hundreds of millions of
      women world-wide. It has recently been used in clinical trials for psychotic
      depression and cancer chemotherapy. Metapristone is the most predominant
      biological active metabolite of mifepristone, and being developed as a novel
      cancer metastasis chemopreventive agent based on its unique pharmacological
      properties. In this study, a novel rapid and sensitive method using UPLC/MS/MS
      was developed and validated for quantitative analysis of metapristone in plasma,
      which used less plasma volume and was demonstrated to be more simple and low-cost
      than the published methods. Metapristone in plasma was recovered by liquid-liquid
      extraction using 1 mL of ethyl acetate and chromatographic separation was carried
      on a C18 column at 35  degrees C, with a gradient mobile phase consisting of
      methanol and water containing 0.1% (v/v) formic acid at a flow rate of 0.3
      mL/min. The mass spectrometric detection was carried out using a triple
      quadrupole system via positive electrospray ionization. Multiple reaction
      monitoring was used for quantitation of m/z transitions from 416.3 to 119.9 for
      metapristone and from 313.1 to 109 for levonorgestrel (internal standard). Good
      linearity (r2> 0.9926) was achieved over a concentration range from 7.1 to 2840
      ng/mL with a lower limit of quantification of 7.1 ng/mL for metapristone. The
      intra- and inter-day variations of the assay were 2.4-10.0% relative standard
      deviation with an accuracy of -5.6 to 8.6% relative error. This newly developed
      method was successfully applied to a pharmacokinetic study that revealed, for the
      first time, that there was a significant difference in pharmacokinetic profile
      between genders.

PMID- 24682016
TI  - A carbon nanotubes based fluorescent aptasensor for highly sensitive detection of
      adenosine deaminase activity and inhibitor screening in natural extracts.
AB  - A carbon nanotubes (CNTs) based fluorescent aptasensor was developed for
      adenosine deaminase (ADA) activity detection and inhibitor screening by using
      adenosine (AD) as the substrate. This sensing system consists of CNTs, AD, split
      anti-AD aptamer fragment and dye-labeled aptamer fragment. In the absence of ADA,
      two aptamer fragments bind simultaneously with AD to form an AD-aptamer complex.
      This AD-aptamer complex cannot adsorb onto CNTs, and has high fluorescence
      intensity. When ADA is introduced into this system, ADA can convert AD into
      inosine, which has not affinity to the split anti-AD aptamer fragment. Thus, the
      split anti-AD aptamer fragments were adsorbed onto CNTs via strong pi-pi stacking
      interactions, resulting in the quenching of the fluorescence of the dye-labeled
      aptamer fragment. The proposed aptasensor can detect ADA activity from 0.005 to
      0.2U/mL with a low detection limit of 0.002 U/mL. Moreover, it has been also
      demonstrated that this CNTs-based fluorescence aptasensor is suitable for ADA
      inhibitor screening from traditional Chinese medicine (TCM). Considering the
      superior sensitivity and specificity, the proposed CNTs-based fluorescent
      aptasensor can be expected to provide a simple, cost-effective and sensitive
      platform for the detection of ADA activity and screening of potential drugs.

PMID- 24682017
TI  - Locating the binding sites of antitumor drug tamoxifen and its metabolites with
      DNA.
AB  - We located the binding sites of antitumor drugs tamoxifen, 4-hydroxytamoxifen and
      endoxifen with calf-thymus DNA. FTIR, CD, UV-vis and fluorescence spectroscopic
      methods as well as molecular modeling were used to characterize the drug binding
      sites, binding constant and the effect of drug binding on DNA stability and
      conformation. Structural analysis showed that tamoxifen and its metabolites bind
      DNA via hydrophobic and hydrophilic interactions with overall binding constants
      of K(tam-DNA)=3.5 (+/-0.2)*104 M-1, K(4-hydroxytam-DNA)=3.3 (+/-0.4) * 104 M-1
      and K(endox)-DNA=2.8 (+/-0.8)*104 M-1. The number of binding sites occupied by
      drug is 1 (tamoxifen), 0.8 (4-hydroxitamoxifen) and 1.2 (endoxifen). Docking
      showed the participation of several nucleobases in drug-DNA complexes with the
      free binding energy of -3.85 (tamoxifen), -4.18 (4-hydroxtamoxifen) and -3.74
      kcal/mol (endoxifen). The order of binding is 4-hydroxy
      tamoxen>tamoxifen>endoxifen. Drug binding did not alter DNA conformation from B
      family structure, while major biopolymer aggregation occurred at high drug
      concentrations. The drug binding mode is correlated with the mechanism of action
      of antitumor activity of tamoxifen and its metabolites.

PMID- 24682018
TI  - Validation of a method for the simultaneous quantification of chloroquine,
      desethylchloroquine and primaquine in plasma by HPLC-DAD.
AB  - One of the most important aspects regarding the therapeutic efficacy of
      antimalarials is its quantification in biologic fluids. The detection and
      measurement of antimalarial drug levels is important for demonstrating (1)
      adequate absorption of the drug being given, (2) compliance in taking the full
      regimen required for treatment and (3) the level of drug in the blood at any time
      during the test period that parasites reappear. There is a lack of validated
      methods that simultaneously quantify different antimalarials administered at the
      same time, such as the use of chloroquine (CQ) and primaquine (PQ) in infections
      caused by Plasmodium vivax. In this study, a bioanalytical method was validated
      for the simultaneous quantification of primaquine (PQ), chloroquine (CQ) and
      desethylchloroquine (DSCQ) in human plasma using liquid-liquid extraction and
      high performance liquid chromatography with a diode array detector (HPLC-DAD).
      The PQ was evaluated over a concentration range of 100-3000 nM and the CQ and
      DSCQ was evaluated over a concentration range of 20-2000 nM. The selectivity of
      the method was verified by checking for interference by commonly used
      antimalarials and plasma samples. The accuracy and precision of the method was
      assessed for drugs spiked into human plasma and recoveries of 83.7%, 92.3%, and
      76.5% were obtained for CQ, DSCQ, and PQ, respectively. The applicability of this
      method was also demonstrated with blood samples from patients with vivax malaria
      that received combination CQ plus PQ treatment. The simultaneous detection and
      accurate measurement of CQ, DSCQ, and PQ levels in human plasma provides an
      important and economical method for validating and monitoring
      sensitivity/resistance of P. vivax to more common treatment regimen.

PMID- 24682020
TI  - Organic-free colloidal semiconductor nanocrystals as luminescent sensors for
      metal ions and nitroaromatic explosives.
AB  - Exposed surfaces of organic-free colloidal semiconductor nanocrystals act as
      generic luminescent sensors for multiple analytes. S(2-) capped CdSe/CdSeS/CdS
      core/gradient-shell/shell nanocrystals are turn-on sensors for Cd(2+) ions (110
      pM) in an aqueous medium with physiological pH 7.4. A similar organic-free
      semiconductor nanocrystal shows luminescence turn-off sensing for 2,4,6
      trinitrophenol, a known explosive. 

PMID- 24682019
TI  - Cyclotide structure-activity relationships: qualitative and quantitative
      approaches linking cytotoxic and anthelmintic activity to the clustering of
      physicochemical forces.
AB  - Cyclotides are a family of plant-derived proteins that are characterized by a
      cyclic backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK)
      motif makes them exceptionally resistant to thermal, chemical, and enzymatic
      degradation. Cyclotides exert much of their biological activity via interactions
      with cell membranes. In this work, we qualitatively and quantitatively analyze
      the cytotoxic and anthelmintic membrane activities of cyclotides. The qualitative
      and quantitative models describe the potency of cyclotides using four simple
      physicochemical terms relevant to membrane contact. Specifically, surface areas
      of the cyclotides representing lipophilic and hydrogen bond donating properties
      were quantified and their distribution across the molecular surface was
      determined. The resulting quantitative structure-activity relation (QSAR) models
      suggest that the activity of the cyclotides is proportional to their lipophilic
      and positively charged surface areas, provided that the distribution of these
      surfaces is asymmetric. In addition, we qualitatively analyzed the
      physicochemical differences between the various cyclotide subfamilies and their
      effects on the cyclotides' orientation on the membrane and membrane activity. 

PMID- 24682021
TI  - Perceptions among women with gestational diabetes.
AB  - Women with gestational diabetes are at high risk of developing type 2 diabetes,
      which could be prevented or delayed by lifestyle modification. Lifestyle
      interventions need to take into account the specific situation of women with
      gestational diabetes. We aimed to gain a deeper understanding of women's
      experiences of gestational diabetes, their diabetes risk perceptions, and their
      views on type 2 diabetes prevention, to inform future lifestyle interventions. We
      conducted a metasynthesis that included 16 qualitative studies and identified 11
      themes. Factors that require consideration when developing a type 2 diabetes
      prevention intervention in this population include addressing the emotional
      impact of gestational diabetes; providing women with clear and timely information
      about future diabetes risk; and offering an intervention that fits with women's
      multiple roles as caregivers, workers, and patients, and focuses on the health of
      the whole family. 

PMID- 24682022
TI  - Morinda citrifolia leaves enhance osteogenic differentiation and mineralization
      of human periodontal ligament cells.
AB  - This present study investigated the potential of Morinda citrifolia leaf aqueous
      extract to induce osteogenic differentiation and matrix mineralization of human
      periodontal ligament (hPDL) cells. Human periodontal ligament cells were cultured
      in complete medium, ascorbic acid with beta-glycerophosphate, or Morinda
      citrifolia leaf aqueous extract. Morinda citrifolia leaf aqueous extract
      significantly increased alkaline phosphatase activity compared to culturing in
      complete medium or ascorbic acid with beta-glycerophosphate. Matrixcontaining
      mineralized nodules were formed only when the cells were cultured in the presence
      of Morinda citrifolia leaf aqueous extract. These nodules showed positive
      alizarin red S staining and were rich in calcium and phosphorus according to
      energy dispersive X-ray analysis. In conclusion, Morinda citrifolia leaf extract
      promoted osteogenic differentiation and matrix mineralization in human
      periodontal ligament cells, a clear indication of the therapeutic potential of
      Morinda citrifolia leaves in bone and periodontal tissue regeneration. 

PMID- 24682023
TI  - Differentiation potential of osteoblast from cultured C2C12 cells on zirconia
      disk.
AB  - We examined the adaptability of zirconia as a fixture for implants. A mouse
      myoblast cell line (C2C12) was seeded on Ce-TZP and titanium disks, and on poly-L
      lysine-coated glass slides. Proliferation potency was determined by cell counting
      and mineral induction by BMP2 was studied. The osteoblastic differentiation
      potency was determined by alkaline phosphatase (ALP) and alizarin red (ARS)
      staining. ALP activity and calcium concentrations were colorimetrically measured.
      The number of cells on all materials was approximately equal. ALP and ARS
      staining showed densely-stained images, demonstrating the induction of C2C12
      cells to express the osteoblastic phenotype. RT-PCR showed that mRNA expressions
      of type I collagen, osteocalcin, osterix and ALP were up-regulated. With regard
      to ALP activity and calcium concentration of C2C12 cells, no significant
      differences were observed between Ce-TZP and titanium disks. We conclude that Ce
      TZP has the biological activity comparable to titanium and has the utility as
      fixture of dental implants. 

PMID- 24682024
TI  - Salvage treatment of methicillin-resistant staphylococcal endocarditis with
      ceftaroline: a multicentre observational study.

PMID- 24682025
TI  - Packaging commercial CMOS chips for lab on a chip integration.
AB  - Combining integrated circuitry with microfluidics enables lab-on-a-chip (LOC)
      devices to perform sensing, freeing them from benchtop equipment. However, this
      integration is challenging with small chips, as is briefly reviewed with
      reference to key metrics for package comparison. In this paper we present a
      simple packaging method for including mm-sized, foundry-fabricated dies
      containing complementary metal oxide semiconductor (CMOS) circuits within LOCs.
      The chip is embedded in an epoxy handle wafer to yield a level, large-area
      surface, allowing subsequent photolithographic post-processing and microfluidic
      integration. Electrical connection off-chip is provided by thin film metal traces
      passivated with parylene-C. The parylene is patterned to selectively expose the
      active sensing area of the chip, allowing direct interaction with a fluidic
      environment. The method accommodates any die size and automatically levels the
      die and handle wafer surfaces. Functionality was demonstrated by packaging two
      different types of CMOS sensor ICs, a bioamplifier chip with an array of surface
      electrodes connected to internal amplifiers for recording extracellular
      electrical signals and a capacitance sensor chip for monitoring cell adhesion and
      viability. Cells were cultured on the surface of both types of chips, and data
      were acquired using a PC. Long term culture (weeks) showed the packaging
      materials to be biocompatible. Package lifetime was demonstrated by exposure to
      fluids over a longer duration (months), and the package was robust enough to
      allow repeated sterilization and re-use. The ease of fabrication and good
      performance of this packaging method should allow wide adoption, thereby spurring
      advances in miniaturized sensing systems. 

PMID- 24682026
TI  - Comparison of balloon-expandable vs self-expandable valves in patients undergoing
      transcatheter aortic valve replacement: the CHOICE randomized clinical trial.
AB  - IMPORTANCE: Transcatheter aortic valve replacement (TAVR) is an effective
      treatment option for high-risk patients with severe aortic stenosis. Different
      from surgery, transcatheter deployment of valves requires either a balloon
      expandable or self-expandable system. A randomized comparison of these 2 systems
      has not been performed. OBJECTIVE: To determine whether the balloon-expandable
      device is associated with a better success rate than the self-expandable device.
      DESIGN, SETTING, AND PATIENTS: The CHOICE study was an investigator-initiated
      trial in high-risk patients with severe aortic stenosis and an anatomy suitable
      for the transfemoral TAVR procedure. One hundred twenty-one patients were
      randomly assigned to receive a balloon-expandable valve (Edwards Sapien XT) and
      120 were assigned to receive a self-expandable valve (Medtronic CoreValve).
      Patients were enrolled between March 2012 and December 2013 at 5 centers in
      Germany. INTERVENTIONS: Transfemoral TAVR with a balloon-expandable or self
      expandable device. MAIN OUTCOMES AND MEASURES: The primary end point was device
      success, which is a composite end point including successful vascular access and
      deployment of the device and retrieval of the delivery system, correct position
      of the device, intended performance of the heart valve without moderate or severe
      regurgitation, and only 1 valve implanted in the proper anatomical location.
      Secondary end points included cardiovascular mortality, bleeding and vascular
      complications, postprocedural pacemaker placement, and a combined safety end
      point at 30 days, including all-cause mortality, major stroke, and other serious
      complications. RESULTS: Device success occurred in 116 of 121 patients (95.9%) in
      the balloon-expandable valve group and 93 of 120 patients (77.5%) in the self
      expandable valve group (relative risk [RR], 1.24, 95% CI, 1.12-1.37, P < .001).
      This was attributed to a significantly lower frequency of residual more-than-mild
      aortic regurgitation (4.1% vs 18.3%; RR, 0.23; 95% CI, 0.09-0.58; P < .001) and
      the less frequent need for implanting more than 1 valve (0.8% vs 5.8%, P = .03)
      in the balloon-expandable valve group. Cardiovascular mortality at 30 days was
      4.1% in the balloon-expandable valve group and 4.3% in the self-expandable valve
      group (RR, 0.97; 95% CI, 0.29-3.25; P = .99). Bleeding and vascular complications
      were not significantly different, and the combined safety end point occurred in
      18.2% of those in the balloon-expandable valve group and 23.1% of the self
      expandable valve group (RR, 0.79; 95% CI, 0.48-1.30; P = .42). Placement of a new
      permanent pacemaker was less frequent in the balloon-expandable valve group
      (17.3% vs 37.6%, P = .001). CONCLUSIONS AND RELEVANCE: Among patients with high
      risk aortic stenosis undergoing TAVR, the use of a balloon-expandable valve
      resulted in a greater rate of device success than use of a self-expandable valve.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01645202.

PMID- 24682027
TI  - Mutagenesis of the hydrocarbon monooxygenase indicates a metal centre in subunit
      C, and not subunit-B, is essential for copper-containing membrane monooxygenase
      activity.
AB  - The hydrocarbon monooxygenase (HMO) of Mycobacterium NBB4 is a member of the
      copper-containing membrane monooxygenase (CuMMO) superfamily, which also contains
      particulate methane monooxygenases (pMMOs) and ammonia monooxygenases (AMOs).
      CuMMOs have broad applications due to their ability to catalyse the oxidation of
      difficult substrates of environmental and industrial relevance. Most of our
      understanding of CuMMO biochemistry is based on pMMOs and AMOs as models. All
      three available structures are from pMMOs. These share two metal sites: a
      dicopper centre coordinated by histidine residues in subunit-B and a 'variable
      metal' site coordinated by carboxylate and histidine residues from subunit-C. The
      exact nature and role of these sites is strongly debated. Significant barriers to
      progress have been the physiologically specialized nature of methanotrophs and
      autotrophic ammonia-oxidizers, lack of a recombinant expression system for either
      enzyme and difficulty in purification of active protein. In this study we use the
      newly developed HMO model system to perform site-directed mutagenesis on the
      predicted metal-binding residues in the HmoB and HmoC of NBB4 HMO. All mutations
      of predicted HmoC metal centre ligands abolished enzyme activity. Mutation of a
      predicted copper-binding residue of HmoB (B-H155V) reduced activity by 81 %.
      Mutation of a site that shows conservation within physiologically defined
      subgroups of CuMMOs was shown to reduce relative HMO activity towards larger
      alkanes. The study demonstrates that the modelled dicopper site of subunit-B is
      not sufficient for HMO activity and that a metal centre predicted to be
      coordinated by residues in subunit-C is essential for activity. 

PMID- 24682028
TI  - Response to "clinically actionable genotypes among Brazilians".

PMID- 24682029
TI  - Prediction of clinical irrelevance of PK differences in atorvastatin using PK/PD
      models derived from literature-based meta-analyses.
AB  - To support the development of a fixed-dose combination (FDC) of ezetimibe and
      atorvastatin for the treatment of dyslipidemia, bioequivalence (BE) studies were
      conducted across a combined dose range (10/10, 10/20, 10/40, and 10/80 mg of
      ezetimibe/atorvastatin). In the BE trials, all parameters met traditional BE
      bounds except for atorvastatin peak plasma concentration (Cmax) at two
      intermediate doses. Literature-based metadata analysis predicted that the
      observed difference in Cmax between an ezetimibe+atorvastatin FDC and
      coadministration of these agents translates directly into a non-clinically
      significant change of <1.2% absolute difference in the percentage lowering of low
      density-lipoprotein cholesterol . Both FDC doses were confirmed to be clinically
      equivalent to coadministration in the subsequent clinical equivalence trials.
      These data suggest that modeling of dose-response relationships may be useful in
      predicting clinical equivalence, lowering cost/timelines through effective
      powering of studies, and predicting the effectiveness of new dosage formulations
      without the need for additional clinical efficacy trials in regulatory settings. 

PMID- 24682030
TI  - Using positron emission tomography to study transporter-mediated drug-drug
      interactions in tissues.
AB  - Drug disposition is highly regulated by membrane transporters. Some transporter
      mediated drug-drug interactions (DDIs) may not manifest themselves in changes in
      systemic exposure but rather in changes in tissue exposure of drugs. To better
      assess the impact of transporter-mediated DDIs in tissues, positron emission
      tomography (PET)-a noninvasive imaging method--plays an increasingly important
      role. In this article, we provide examples of how PET can be used to assess
      transporter-mediated DDIs in different organs.

PMID- 24682031
TI  - Effect of mineral constituents in the bioleaching of uranium from uraniferous
      sedimentary rock samples, Southwestern Sinai, Egypt.
AB  - Bioleaching, like Biotechnology uses microorganisms to extract metals from their
      ore materials, whereas microbial activity has an appreciable effect on the
      dissolution of toxic metals and radionuclides. Bioleaching of uranium was carried
      out with isolated fungi from uraniferous sedimentary rocks from Southwestern
      Sinai, Egypt. Eight fungal species were isolated from different grades of
      uraniferous samples. The bio-dissolution experiments showed that Aspergillus
      niger and Aspergillus terreus exhibited the highest leaching efficiencies of
      uranium from the studied samples. Through monitoring the bio-dissolution process,
      the uranium grade and mineralogic constituents of the ore material proved to play
      an important role in the bioleaching process. The tested samples asserted that
      the optimum conditions of uranium leaching are: 7 days incubation time, 3% pulp
      density, 30  degrees C incubation temperature and pH 3. Both fungi produced the
      organic acids, namely; oxalic, acetic, citric, formic, malonic, galic and
      ascorbic in the culture filtrate, indicating an important role in the bioleaching
      processes. 

PMID- 24682032
TI  - Third trimester fetal hemodynamics and cardiovascular outcomes in childhood: the
      Generation R study.
AB  - OBJECTIVE: Low birth weight is associated with cardiovascular disease in
      adulthood. Hemodynamic adaptations related to fetal growth restriction may
      underlie these associations, through persistent influences on cardiovascular
      development. We examined the associations of third trimester fetal hemodynamics
      with cardiovascular outcomes in childhood. METHODS: In a prospective cohort study
      among 917 pregnant women and their children, we measured fetal growth, and fetal
      arterial and cardiac hemodynamic variables with ultrasound and Doppler
      examinations at a gestational age of 30.3 (95% range 28.8-32.3) weeks. At the age
      of 6 years, we measured blood pressure, carotid-femoral pulse wave velocity, and
      left cardiac structures and function. RESULTS: We observed that fetal
      hemodynamics were not associated with childhood blood pressure and carotid
      femoral pulse wave velocity. The fetal aorta ascendens diameter and left cardiac
      output were positively associated with childhood aortic root diameter [0.14
      standard deviation score (SDS), 95% confidence interval (CI) 0.07-0.22 and 0.08
      SDS, 95% CI 0.01-0.15 per SDS change in diameter and output, respectively]. Fetal
      left ventricular diastolic filling pattern was inversely associated with aortic
      root diameter (-0.07 SDS, 95% CI -0.13 to 0.00 per SDS change in E/A ratio) at 6
      years. Analyses adjusted and stratified for estimated fetal weight showed no
      differences in results. CONCLUSION: Our results suggest that third trimester
      fetal vascular resistance parameters do not affect blood pressure or arterial
      stiffness in childhood. Fetal cardiac functional and structural measures are
      associated with cardiac outcomes in childhood. Whether these early adaptations
      lead to greater risks of cardiovascular disease should be further studied.

PMID- 24682034
TI  - Efficient visible upconversion luminescence in Er3+ and Er3+/Yb3+ co-doped Y2O3
      phosphors obtained by solution combustion reaction.
AB  - Combustion derived Er(3+) -doped Y2O3 and Er(3+)/Yb(3+)co-doped Y2O3 powders have
      been characterized by X-ray diffraction, energy dispersive X-ray analysis,
      Fourier transform infrared spectroscopy and laser excited spectroscopy. Formation
      of Y2O3 phosphor was confirmed by X-ray diffraction and energy dispersive X-ray
      analysis. The vibrational properties of Y2O3 powder was studied by Fourier
      transform infrared spectroscopy. The luminescence spectra of Er(3+) -doped and
      Er(3+)/Yb(3+) co-doped Y2O3 powders were studied under 379nm excitation. The
      strong up-conversion luminescence for Er(3+) -doped and Er(3+)/Yb(3+) co-doped
      Y2O3 powders have been observed under 978nm laser excitation. The effect of
      Yb(3+) addition on optical and luminescence properties of Er(3+):Y2O3 powders
      were studied. The ratio of red to green intensity has been enhanced when Er(3+) 
      doped Y2O3 is co-doped with Yb(3+) ions. The effect of co-doping of Yb(3+) ions
      on the visible luminescence intensity of Er(3+) has been studied and the
      mechanism responsible for the variation in the green and red intensity is
      discussed. 

PMID- 24682033
TI  - The mechanism for processing random-dot motion at various speeds in early visual
      cortices.
AB  - All moving objects generate sequential retinotopic activations representing a
      series of discrete locations in space and time (motion trajectory). How direction
      selective neurons in mammalian early visual cortices process motion trajectory
      remains to be clarified. Using single-cell recording and optical imaging of
      intrinsic signals along with mathematical simulation, we studied response
      properties of cat visual areas 17 and 18 to random dots moving at various speeds.
      We found that, the motion trajectory at low speed was encoded primarily as a
      direction signal by groups of neurons preferring that motion direction. Above
      certain transition speeds, the motion trajectory is perceived as a spatial
      orientation representing the motion axis of the moving dots. In both areas
      studied, above these speeds, other groups of direction-selective neurons with
      perpendicular direction preferences were activated to encode the motion
      trajectory as motion-axis information. This applied to both simple and complex
      neurons. The average transition speed for switching between encoding motion
      direction and axis was about 31 degrees /s in area 18 and 15 degrees /s in area
      17. A spatio-temporal energy model predicted the transition speeds accurately in
      both areas, but not the direction-selective indexes to random-dot stimuli in area
      18. In addition, above transition speeds, the change of direction preferences of
      population responses recorded by optical imaging can be revealed using vector
      maximum but not vector summation method. Together, this combined processing of
      motion direction and axis by neurons with orthogonal direction preferences
      associated with speed may serve as a common principle of early visual motion
      processing. 

PMID- 24682035
TI  - Identification of novel reference genes based on MeSH categories.
AB  - Transcriptome experiments are performed to assess protein abundance through mRNA
      expression analysis. Expression levels of genes vary depending on the
      experimental conditions and the cell response. Transcriptome data must be diverse
      and yet comparable in reference to stably expressed genes, even if they are
      generated from different experiments on the same biological context from various
      laboratories. In this study, expression patterns of 9090 microarray samples
      grouped into 381 NCBI-GEO datasets were investigated to identify novel candidate
      reference genes using randomizations and Receiver Operating Characteristic (ROC)
      curves. The analysis demonstrated that cell type specific reference gene sets
      display less variability than a united set for all tissues. Therefore,
      constitutively and stably expressed, origin specific novel reference gene sets
      were identified based on their coefficient of variation and percentage of
      occurrence in all GEO datasets, which were classified using Medical Subject
      Headings (MeSH). A large number of MeSH grouped reference gene lists are
      presented as novel tissue specific reference gene lists. The most commonly
      observed 17 genes in these sets were compared for their expression in 8
      hepatocellular, 5 breast and 3 colon carcinoma cells by RT-qPCR to verify tissue
      specificity. Indeed, commonly used housekeeping genes GAPDH, Actin and EEF2 had
      tissue specific variations, whereas several ribosomal genes were among the most
      stably expressed genes in vitro. Our results confirm that two or more reference
      genes should be used in combination for differential expression analysis of large
      scale data obtained from microarray or next generation sequencing studies.
      Therefore context dependent reference gene sets, as presented in this study, are
      required for normalization of expression data from diverse technological
      backgrounds. 

PMID- 24682036
TI  - Evaluation of polycaprolactone matrices for the intravaginal delivery of
      metronidazole in the treatment of bacterial vaginosis.
AB  - Microporous, poly (E-caprolactone) (PCL) matrices loaded with the antibacterial,
      metronidazole were produced by rapidly cooling suspensions of drug powder in PCL
      solutions in acetone. Drug incorporation in the matrices increased from 2.0% to
      10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w
      measured with respect to the PCL content. Drug loading efficiencies of 40-53%
      were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was
      recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF),
      due to the presence of large amounts of drug on matrix surface as revealed by
      Raman microscopy. Gradual release of around 80% of the drug content occurred over
      the following 12 days. Metronidazole released from PCL matrices in SVF retained
      antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97%
      compared to the free drug. Basic modelling predicted that the concentrations of
      metronidazole released into vaginal fluid in vivo from a PCL matrix in the form
      of an intravaginal ring would exceed the minimum inhibitory concentration of
      metronidazole against G. vaginalis. These findings recommend further
      investigation of PCL matrices as intravaginal devices for controlled delivery of
      metronidazole in the treatment and prevention of bacterial vaginosis.

PMID- 24682037
TI  - Guiding the orientation of smooth muscle cells on random and aligned
      polyurethane/collagen nanofibers.
AB  - Fabricating scaffolds that can simulate the architecture and functionality of
      native extracellular matrix is a huge challenge in vascular tissue engineering.
      Various kinds of materials are engineered via nano-technological approaches to
      meet the current challenges in vascular tissue regeneration. During this study,
      nanofibers from pure polyurethane and hybrid polyurethane/collagen in two
      different morphologies (random and aligned) and in three different ratios of
      polyurethane:collagen (75:25; 50:50; 25:75) are fabricated by electrospinning.
      The fiber diameters of the nanofibrous scaffolds are in the range of 174-453 nm
      and 145-419 for random and aligned fibers, respectively, where they closely mimic
      the nanoscale dimensions of native extracellular matrix. The aligned
      polyurethane/collagen nanofibers expressed anisotropic wettability with
      mechanical properties which is suitable for regeneration of the artery. After 12
      days of human aortic smooth muscle cells culture on different scaffolds, the
      proliferation of smooth muscle cells on hybrid polyurethane/collagen (3:1)
      nanofibers was 173% and 212% higher than on pure polyurethane scaffolds for
      random and aligned scaffolds, respectively. The results of cell morphology and
      protein staining showed that the aligned polyurethane/collagen (3:1) scaffold
      promote smooth muscle cells alignment through contact guidance, while the random
      polyurethane/collagen (3:1) also guided cell orientation most probably due to the
      inherent biochemical composition. Our studies demonstrate the potential of
      aligned and random polyurethane/collagen (3:1) as promising substrates for
      vascular tissue regeneration.

PMID- 24682039
TI  - Temperature and cyanobacterial bloom biomass influence phosphorous cycling in
      eutrophic lake sediments.
AB  - Cyanobacterial blooms frequently occur in freshwater lakes, subsequently,
      substantial amounts of decaying cyanobacterial bloom biomass (CBB) settles onto
      the lake sediments where anaerobic mineralization reactions prevail. Coupled Fe/S
      cycling processes can influence the mobilization of phosphorus (P) in sediments,
      with high releases often resulting in eutrophication. To better understand
      eutrophication in Lake Taihu (PRC), we investigated the effects of CBB and
      temperature on phosphorus cycling in lake sediments. Results indicated that added
      CBB not only enhanced sedimentary iron reduction, but also resulted in a change
      from net sulfur oxidation to sulfate reduction, which jointly resulted in a spike
      of soluble Fe(II) and the formation of FeS/FeS2. Phosphate release was also
      enhanced with CBB amendment along with increases in reduced sulfur. Further
      release of phosphate was associated with increases in incubation temperature. In
      addition, CBB amendment resulted in a shift in P from the Fe-adsorbed P and the
      relatively unreactive Residual-P pools to the more reactive Al-adsorbed P, Ca
      bound P and organic-P pools. Phosphorus cycling rates increased on addition of
      CBB and were higher at elevated temperatures, resulting in increased phosphorus
      release from sediments. These findings suggest that settling of CBB into
      sediments will likely increase the extent of eutrophication in aquatic
      environments and these processes will be magnified at higher temperatures. 

PMID- 24682038
TI  - Clinical comparison of distal pancreatectomy with or without splenectomy: a meta
      analysis.
AB  - OBJECTIVE: A distal pancreatectomy has routinely been used for removing
      benign/borderline malignant tumors of the body and tail of the pancreas; however,
      controversy exists whether or not the spleen should be saved. Therefore, we
      conducted this meta-analysis for comparing the clinical outcomes of patients who
      underwent distal pancreatectomy with or without splenectomy. METHODS: A
      literature research from the databases of Medline, Embase, and Cochrane library
      was performed to evaluate and compare the clinical outcomes between spleen
      preserving distal pancreatectomy (SPDP) and distal pancreatectomy with
      splenectomy (DPS). Pooled odds ratio (OR) and weighted mean difference (WMD) with
      95% confidence interval (95% CI) were calculated using fixed-effects or random
      effects models. RESULTS: Eleven non-randomized controlled studies involving 897
      patients were selected to satisfy the inclusion criteria; 355 patients underwent
      SPDP and 542 patients underwent DPS. Compared with DPS, SPDP required a shorter
      hospital stay (WMD = 1.16, 95% CI = -2.00 to -0.31, P = 0.007), and had a lower
      incidence of intra-abdominal abscesses (OR = 0.48, 95% CI = 0.27 to 0.83, P =
      0.009). In addition, spleen infarctions occurred in SPDP, most of which involved
      use of the Warshaw method for preserving the spleen. There were no differences
      between the SPDP and DPS groups with respect to operative time, operative blood
      loss, requirement for blood transfusion, pancreatic fistulas, thromboses, post
      operative bleeding, wound infections and re-operation rates. CONCLUSION: SPDP
      should be performed due to the benefits of the immune system and quick post
      operative recovery. It is also essential to preserve the splenic artery and vein.
      Large randomized controlled trials are further needed to verify the results of
      this meta-analysis.

PMID- 24682040
TI  - Predictive combinatorial design of mRNA translation initiation regions for
      systematic optimization of gene expression levels.
AB  - Balancing the amounts of enzymes is one of the important factors to achieve
      optimum performance of a designed metabolic pathway. However, the random
      mutagenesis approach is impractical since it requires searching an unnecessarily
      large number of variants and often results in searching a narrow range of
      expression levels which are out of optimal level. Here, we developed a predictive
      combinatorial design method, called UTR Library Designer, which systematically
      searches a large combinatorial space of expression levels. It accomplishes this
      by designing synthetic translation initiation region of mRNAs in a predictive way
      based on a thermodynamic model and genetic algorithm. Using this approach, we
      successfully enhanced lysine and hydrogen production in Escherichia coli. Our
      method significantly reduced the number of variants to be explored for covering
      large combinatorial space and efficiently enhanced pathway efficiency, thereby
      facilitating future efforts in metabolic engineering and synthetic biology. 

PMID- 24682041
TI  - International scientific collaboration in HIV and HPV: a network analysis.
AB  - Research endeavours require the collaborative effort of an increasing number of
      individuals. International scientific collaborations are particularly important
      for HIV and HPV co-infection studies, since the burden of disease is rising in
      developing countries, but most experts and research funds are found in developed
      countries, where the prevalence of HIV is low. The objective of our study was to
      investigate patterns of international scientific collaboration in HIV and HPV
      research using social network analysis. Through a systematic review of the
      literature, we obtained epidemiological data, as well as data on countries and
      authors involved in co-infection studies. The collaboration network was analysed
      in respect to the following: centrality, density, modularity, connected
      components, distance, clustering and spectral clustering. We observed that for
      many low- and middle-income countries there were no epidemiological estimates of
      HPV infection of the cervix among HIV-infected individuals. Most studies found
      only involved researchers from the same country (64%). Studies derived from
      international collaborations including high-income countries and either low- or
      middle-income countries had on average three times larger sample sizes than those
      including only high-income countries or low-income countries. The high global
      clustering coefficient (0.9) coupled with a short average distance between
      researchers (4.34) suggests a "small-world phenomenon." Researchers from high
      income countries seem to have higher degree centrality and tend to cluster
      together in densely connected communities. We found a large well-connected
      community, which encompasses 70% of researchers, and 49 other small isolated
      communities. Our findings suggest that in the field of HIV and HPV, there seems
      to be both room and incentives for researchers to engage in collaborations
      between countries of different income-level. Through international collaboration
      resources available to researchers in high-income countries can be efficiently
      used to enroll more participants in low- and middle-income countries. 

PMID- 24682042
TI  - alpha-Spinasterol from Melandrium firmum attenuates benign prostatic hyperplasia
      in a rat model.
AB  - Spinasterol, a biologically active compound, exhibits a number of pharmacological
      activities, including antitumor, antiulcerogenic and anticarcinogenic activity,
      and originates from the aerial parts of Aster scaber Thunb (Asteraceae). The
      present study investigated whether alpha-spinasterol isolated from Melandrium
      firmum Rohrbach could prevent benign prostatic hyperplasia (BPH) induced by
      testosterone propionate (TP) in rats. Male Wistar rats were randomly divided into
      four groups of eight rats following castration. A negative control group received
      subcutaneous injections of corn oil. Treatments were administered orally 1 h
      prior to TP injection. All the rats were sacrificed at the scheduled termination
      time and their prostates were removed, cleaned and weighed. The prostate size
      ratio (prostate weight/rat body weight) was then calculated. Additional
      histopathological examinations were conducted, and the levels of TP and
      dihydrotestosterone (DHT) in the serum and prostate were measured. TP
      significantly increased the prostate size ratio (P<0.01), and DHT and
      testosterone levels in the serum and prostate. The TP-induced increase was
      significantly inhibited in alpha-spinasterol-treated rats when compared with the
      negative controls (P<0.05). In addition, histopathological examination
      demonstrated that alpha-spinasterol treatment suppressed TP-induced prostatic
      hyperplasia. It is concluded that alpha-spinasterol can prevent TP-induced
      prostatic hyperplasia and may be beneficial in the management of BPH.

PMID- 24682043
TI  - Pharmacological mobilization of endogenous stem cells significantly promotes skin
      regeneration after full-thickness excision: the synergistic activity of AMD3100
      and tacrolimus.
AB  - Stem cell therapy has shown promise in treating a variety of pathologies
      including skin wounds, but practical applications remain elusive. Here, we
      demonstrate that endogenous stem cell mobilization produced by AMD3100 and low
      dose tacrolimus is able to reduce by 25% the time of complete healing of full
      thickness wounds created by surgical excision. Equally important, healing was
      accompanied by reduced scar formation and regeneration of hair follicles.
      Searching for mechanisms, we found that AMD3100 combined with low-dose tacrolimus
      mobilized increased number of lineage-negative c-Kit+, CD34+, and CD133+ stem
      cells. Low-dose tacrolimus also increased the number of SDF-1-bearing macrophages
      in the wound sites amplifying the "pull" of mobilized stem cells into the wound.
      Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced
      capillary and hair follicle neogenesis, contributing to more rapid and perfect
      healing. Our findings offer a significant therapeutic approach to wound healing
      and tissue regeneration. 

PMID- 24682046
TI  - [Randomized controlled trial of pancreaticoduodenectomy with and without
      drainage].

PMID- 24682045
TI  - Identification of CHRNA5 rare variants in African-American heavy smokers.
AB  - BACKGROUND: The common CHRNA5 mis-sense coding single-nucleotide polymorphism
      (SNP) rs16969968:G>A (D398N) has repeatedly been shown to confer risk for heavy
      smoking in individuals who carry the 'A' allele (encoding the 398N amino acid).
      The mis-sense SNP has a minor allele frequency of ~40% in European-Americans, but
      only ~7% in African-Americans (http://www.ncbi.nlm.nih.gov/projects/SNP/). We
      reasoned that there might be other mis-sense variants among African-Americans
      that could confer the heavy smoking phenotype (defined here as >=20 cigarettes
      per day), perhaps in a manner similar to that of the D398N polymorphism in
      Europeans. MATERIALS AND METHODS: As such, we resequenced 250 African-American
      heavy smokers, most of whom were homozygous 'G' at rs16969968:G>A (minor allele
      frequency of 9.6% within the population). RESULTS: Although many novel coding
      SNPs were not observed, we report an interesting, although rare (perhaps
      personal), variant in CHRNA5 that could result in nonsense-mediated decay of the
      aberrant transcript. CONCLUSION: We conclude that, in African-Americans, variants
      (common or rare) in genes other than CHRNA5 most likely contribute toward the
      nicotine-dependent phenotype, either independently or in combination with
      variants in CHRNA5. The functional significance, on CHRNA5 expression or protein
      function, of the variants found here should be determined in future studies.

PMID- 24682047
TI  - Mass spectrometry for real-time quantitative breath analysis.
AB  - Breath analysis research is being successfully pursued using a variety of
      analytical methods, prominent amongst which are gas chromatography with mass
      spectrometry, GC-MS, ion mobility spectrometry, IMS, and the fast flow and flow
      drift tube techniques called selected ion flow tube mass spectrometry, SIFT-MS,
      and proton transfer reaction mass spectrometry, PTR-MS. In this paper the case is
      made for real-time breath analysis by obviating sample collection into bags or
      onto traps that can suffer from partial degradation of breath metabolites or the
      introduction of impurities. Real-time analysis of a broad range of volatile
      chemical compounds can be best achieved using SIFT-MS and PTR-MS, which are
      sufficiently sensitive and rapid to allow the simultaneous analyses of several
      trace gas metabolites in single breath exhalations. The basic principles and the
      ion chemistry that underpin these two analytical techniques are briefly described
      and the differences between them, including their respective strengths and
      weaknesses, are revealed, especially with reference to the analysis of the
      complex matrix that is exhaled breath. A recent innovation is described that
      combines time-of-flight mass spectrometry with the proton transfer flow-drift
      tube reactor, PTR-TOFMS, which provides greater resolution in the analytical mass
      spectrometer and allows separation of protonated isobaric molecules. Examples are
      presented of some recent data that well illustrate the quality and real-time
      feature of SIFT-MS and PTR-MS for the analysis of exhaled breath for
      physiological/biochemical/pharmacokinetics studies and for the identification and
      quantification of biomarkers relating to specific disease states. 

PMID- 24682048
TI  - Predictive design of engineered multifunctional solid catalysts.
AB  - The ability to devise and design multifunctional active sites at the nanoscale,
      by drawing on the intricate ability of enzymes to evolve single-sites with
      distinctive catalytic function, has prompted complimentary and concordant
      developments in the field of catalyst design and in situ operando spectroscopy.
      Innovations in design-application approach have led to a more fundamental
      understanding of the nature of the active site and its mechanistic influence at a
      molecular level, that have enabled robust structure-property correlations to be
      established, which has facilitated the dextrous manipulation and predictive
      design of redox and solid-acid sites for industrially-significant, sustainable
      catalytic transformations. 

PMID- 24682049
TI  - City block distance and rough-fuzzy clustering for identification of co-expressed
      microRNAs.
AB  - The microRNAs or miRNAs are short, endogenous RNAs having ability to regulate
      mRNA expression at the post-transcriptional level. Various studies have revealed
      that miRNAs tend to cluster on chromosomes. The members of a cluster that are in
      close proximity on chromosomes are highly likely to be processed as co
      transcribed units. Therefore, a large proportion of miRNAs are co-expressed.
      Expression profiling of miRNAs generates a huge volume of data. Complicated
      networks of miRNA-mRNA interaction increase the challenges of comprehending and
      interpreting the resulting mass of data. In this regard, this paper presents a
      clustering algorithm in order to extract meaningful information from miRNA
      expression data. It judiciously integrates the merits of rough sets, fuzzy sets,
      the c-means algorithm, and the normalized range-normalized city block distance to
      discover co-expressed miRNA clusters. While the membership functions of fuzzy
      sets enable efficient handling of overlapping partitions in a noisy environment,
      the concept of lower and upper approximations of rough sets deals with
      uncertainty, vagueness, and incompleteness in cluster definition. The city block
      distance is used to compute the membership functions of fuzzy sets and to find
      initial partition of a data set, and therefore helps to handle minute differences
      between two miRNA expression profiles. The effectiveness of the proposed
      approach, along with a comparison with other related methods, is demonstrated for
      several miRNA expression data sets using different cluster validity indices.
      Moreover, the gene ontology is used to analyze the functional consistency and
      biological significance of generated miRNA clusters. 

PMID- 24682050
TI  - Charge transfer optical absorption and fluorescence emission of 4-(9
      acridyl)julolidine from long-range-corrected time dependent density functional
      theory in polarizable continuum approach.
AB  - A long-range-corrected time-dependent density functional theory (LC-TDDFT) in
      combination with polarizable continuum model (PCM) have been applied to study
      charge transfer (CT) optical absorption and fluorescence emission energies basing
      on parameterized LC-BLYP xc-potential. The molecule of 4-(9-acridyl)julolidine
      selected for this study represents typical CT donor-acceptor dye with strongly
      solvent dependent optical absorption and fluorescence emission spectra. The
      result of calculations are compared with experimental spectra reported in the
      literature to derive an optimal value of the model screening parameter omega. The
      first absorption band appears to be quite well predictable within DFT/TDDFT/PCM
      with the screening parameter omega to be solvent independent (omega ~ 0.245 Bohr(
      1)) whereas the fluorescence emission exhibits a strong dependence on the range
      separation with omega-value varying on a rising solvent polarity from about 0.225
      to 0.151 Bohr(-1). Dipolar properties of the initial state participating in the
      electronic transition have crucial impact on the effective screening.

PMID- 24682051
TI  - Synthesis, characterization and multi-spectroscopic DNA interaction studies of a
      new platinum complex containing the drug metformin.
AB  - A new platinum(II) complex; [Pt(Met)(DMSO)Cl]Cl in which Met = metformin and
      DMSO: dimethylsulfoxide, was synthesized and characterized by (1)H NMR, IR, UV
      Vis spectra, molar conductivity and computational methods. Binding interaction of
      this complex with calf thymus (CT) DNA has been investigated by using absorption,
      emission, circular dichroism, viscosity measurements, differential pulse
      voltammetry and cleavage studies by agarose gel electrophoresis. UV-Vis
      absorption studies showed hyperchromism. CD studies showed less perturbation on
      the base stacking and helicity bands in the CD spectrum of CT-DNA (B->C
      structural transition). In fluorimeteric studies, the Pt(II) complex can bind
      with DNA-NR complex and forms a new non-fluorescence adduct. The anodic peak
      current in the differential pulse voltammogram of the Pt(II) complex decreased
      gradually with the addition of DNA. Cleavage experiments showed that the Pt(II)
      complex does not induce any cleavage under the experimental setup. Finally all
      results indicated that Pt(II) complex interact with DNA via groove binding mode.

PMID- 24682052
TI  - Synthesis, spectral, electrochemical and X-ray single crystal studies on Ni(II)
      and Co(II) complexes derived from 1-benzoyl-3-(4-methylpyridin-2-yl) thiourea.
AB  - 1-Benzoyl-3-(4-methylpyridin-2-yl) thiourea ligand was coordinated with Ni(II)
      and Co(II) perchlorate salts to isolate complexes. All the prepared compounds are
      deliberately investigated by all possible spectral tools. A comparative study for
      IR spectra reveals the neutral bidentate coordinating nature of the ligand
      towards the two metal ions. The UV/Vis spectra of the complexes display d-d
      transition bands proposed an octahedral geometry for the complexes. MS analysis
      data are concerned especially with the base peak which is corresponding to
      C28H25N6O2S2 M ion. The fragmentation patterns are relatively matched with each
      others. Electrochemical studies were carried out using platinum wire and Ag/AgNO3
      as counter and reference electrodes, respectively. The data reflect the
      irreversible nature of the electrode couple and showed two successive one
      electron transfer process. X-ray single crystal studies are used to verifying the
      octahedral geometry proposed as well as calculating crystal parameters beside the
      structural refinements. 

PMID- 24682053
TI  - A new approach for bisphenol A detection employing fluorosurfactant-capped gold
      nanoparticle-amplified chemiluminescence from cobalt(II) and peroxymonocarbonate.
AB  - In this work, we utilized the nonionic fluorosurfactant-capped gold nanoparticles
      (GNPs) as a novel chemiluminescence (CL) probe for the determination of trace
      bisphenol A. Bisphenol A can induce a sharp decrease in CL intensity from the GNP
      Co(2+)-peroxymonocarbonate (HCO4(-)) system. Under the selected experimental
      conditions, a linear relationship was obtained between the CL intensity and the
      logarithm of concentration of bisphenol A in the range of 0.05-50 MUM (R(2) =
      0.9936), and the detection limit at a signal-to-noise ratio of 3 for bisphenol A
      was 10 nM. The applicability of the proposed method has been validated by
      determining bisphenol A in real polycarbonate samples with satisfactory results.
      The recoveries for bisphenol A in spiked samples were found to be between 94.4%
      and 105.0%. The relative standard deviation (RSD) for 12 repeated measurements of
      0.5 MUM bisphenol A was 2.2%. The proposed method described herein was simple,
      selective and obviated the need of extensive sample pretreatment.

PMID- 24682054
TI  - Hyper-Rayleigh scattering from gold nanoparticles: effect of size and shape.
AB  - We report hyper-Rayleigh scattering (HRS) properties of gold nanoparticles (GNPs)
      of five different shapes, quasi-spherical (~10 and ~20 nm diameter), rod (aspect
      ratio ~2), and branched shapes, tetrapod, flower and star with 800 nm, 150 fs
      laser excitation. Using ~10 nm spherical GNPs as reference, the first
      hyperpolarizability (beta) values were calculated for all other shapes. Star and
      flower shaped GNPs have the highest hyperpolarizability (~130 and ~52 times
      higher, respectively), while rod and tetrapod shaped GNPs only have modest
      enhancement (~7 times), which is similar to ~20 nm size quasi-spherical
      particles. These enhancements are attributed to reduced symmetry as well as the
      presence of sharp tips on GNP surface. When the beta values are normalized with
      respect to the number of atoms per particle, the flower and star shaped GNPs
      still have the highest hyperpolarizability values. The polar plots of vertically
      polarized HRS signal as a function of the angle of polarization of the incoming
      incident light shows two lobes, indicating that excitation is predominantly
      dipolar in nature although the size of some GNPs are big enough to show a
      quadrupolar response. It is believed that the presence of sharp tips at the
      surface of these large sized GNPs is responsible for the observed dipolar
      response. This study shows that GNPs having sharp tips might be a better
      candidate when their nonlinear properties are used for sensing applications.

PMID- 24682055
TI  - Synthesis, characterization and spectroscopic investigation of Cr3+ doped
      wollastonite nanophosphor.
AB  - This work explores the preparation of nanocrystalline Cr(3+) (1-5 mol%) doped
      CaSiO3 phosphors by solution combustion process and study of its
      photoluminescence (PL) behavior. The nanopowders are well characterized by powder
      X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM) and Fourier transform infra-red (FTIR) spectroscopy.
      PXRD results confirm monoclinic phase upon calcination at 950 degrees C for 3h.
      SEM micrographs indicates that the powder is highly porous and agglomerated. The
      TEM images show the powder to consist of spherical shaped particles of size ~30
      60 nm. Upon 323 nm excitation, the emission profile of CaSiO3:Cr(3+) exhibits a
      narrow red emission peak at 641nm due to (2)E->(4)A2 transition and broad band at
      722 nm due to (4)T2g->(4)A2g. It is observed that PL intensity increases with
      increase in Cr(3+) concentration and highest PL intensity is observed for 3 mol%
      doped sample. The PL intensity decreases with further increase in Cr(3+) doping.
      This decrease in PL intensity beyond 3 mol% is ascribed to concentration
      quenching. Racah parameters are calculated to describe the effects of electron
      electron repulsion within the crystal lattice. The parameters show 21% reduction
      in the Racah parameter of free ion and the complex, indicating the moderate
      nephelauxetic effect in the lattice.

PMID- 24682056
TI  - The molecular structure of the phosphate mineral beraunite
      Fe(2+)Fe5(3+)(PO4)4(OH)5?4H2O--a vibrational spectroscopic study.
AB  - The mineral beraunite from Boca Rica pegmatite in Minas Gerais with theoretical
      formula Fe(2+)Fe5(3+)(PO4)4(OH)5?4H2O has been studied using a combination of
      electron microscopy with EDX and vibrational spectroscopic techniques. Raman
      spectroscopy identifies an intense band at 990 cm(-1) and 1011 cm(-1). These
      bands are attributed to the PO4(3)(-) nu1 symmetric stretching mode. The nu3
      antisymmetric stretching modes are observed by a large number of Raman bands. The
      Raman bands at 1034, 1051, 1058, 1069 and 1084 together with the Raman bands at
      1098, 1116, 1133, 1155 and 1174 cm(-1) are assigned to the nu3 antisymmetric
      stretching vibrations of PO4(3-) and the HOPO3(2-) units. The observation of
      these multiple Raman bands in the symmetric and antisymmetric stretching region
      gives credence to the concept that both phosphate and hydrogen phosphate units
      exist in the structure of beraunite. The series of Raman bands at 567, 582, 601,
      644, 661, 673, and 687 cm(-1) are assigned to the PO4(3-) nu2 bending modes. The
      series of Raman bands at 437, 468, 478, 491, 503 cm(-1) are attributed to the
      PO4(3-) and HOPO3(2-) nu4 bending modes. No Raman bands of beraunite which could
      be attributed to the hydroxyl stretching unit were observed. Infrared bands at
      3511 and 3359 cm(-1) are ascribed to the OH stretching vibration of the OH units.
      Very broad bands at 3022 and 3299 cm(-1) are attributed to the OH stretching
      vibrations of water. Vibrational spectroscopy offers insights into the molecular
      structure of the phosphate mineral beraunite.

PMID- 24682057
TI  - Phase transformation of calcium oxalate dihydrate-monohydrate: effects of
      relative humidity and new spectroscopic data.
AB  - New data on vibrational properties of calcium oxalates and their controversial
      transformation mechanism are presented. We have focused on whewellite
      (CaC2O4.H2O) and weddellite [CaC2O4.(2+x) H2O], the most common phases of calcium
      oxalate; these compounds occur in many organisms, in kidney stones and in
      particular kinds of films found on the surface of many works of art. Low
      temperature experiments carried out by Fourier transform infrared spectroscopy
      have highlighted both the high structural order in the crystalline state of
      whewellite and the disordered distribution of the zeolitic water molecules in
      weddellite. The synthesised nanocrystals of weddellite have been kept under
      different hygrometric conditions in order to study, by X-ray powder diffraction,
      the role of "external" water molecules on their stability. Moreover, in order to
      identify the different kinds of water molecules, a re-investigation, supported by
      quantum chemical calculations, of the observed vibrational spectra (IR and Raman)
      of whewellite has been conducted. 

PMID- 24682058
TI  - Natural dye extract of lawsonia inermis seed as photo sensitizer for titanium
      dioxide based dye sensitized solar cells.
AB  - Natural dye extract of lawsonia inermis seed were used as photo sensitizer to
      fabricate titanium dioxide nanoparticles based dye sensitized solar cells. Pure
      titanium dioxide (TiO2) nanoparticles in anatase phase were synthesized by sol
      gel technique and pre dye treated TiO2 nanoparticles were synthesized using
      modified sol-gel technique by mixing lawsone pigment rich natural dye during the
      synthesis itself. This pre dye treatment with natural dye has yielded colored
      TiO2 nanoparticles with uniform adsorption of natural dye, reduced agglomeration,
      less dye aggregation and improved morphology. The pure and pre dye treated TiO2
      nanoparticles were subjected to structural, optical, spectral and morphological
      studies. Dye sensitized solar cells (DSSC) fabricated using the pre dye treated
      and pure TiO2 nanoparticles sensitized by natural dye extract of lawsonia inermis
      seed showed a promising solar light to electron conversion efficiency of 1.47%
      and 1% respectively. The pre dye treated TiO2 based DSSC showed an improved
      efficiency of 47% when compared to that of conventional DSSC. 

PMID- 24682059
TI  - Synthesis, thermal and spectroscopic behaviors of metal-drug complexes: La(III),
      Ce(III), Sm(III) and Y(III) amoxicillin trihydrate antibiotic drug complexes.
AB  - The metal complexes of Amoxicillin trihydrate with La(III), Ce(III), Sm(III) and
      Y(III) are synthesized with 1:1 (metal:Amox) molar ratio. The suggested formula
      structures of the complexes are based on the results of the elemental analyses,
      molar conductivity, (infrared, UV-visible and fluorescence) spectra, effective
      magnetic moment in Bohr magnetons, as well as the thermal analysis (TG), and
      characterized by X-ray powder diffraction (XRD) and scanning electron microscopy
      (SEM). The results obtained suggested that Amoxicillin reacted with metal ions as
      tridentate ligands, coordinating the metal ion through its amino, imino, and beta
      lactamic carbonyl. The kinetic thermodynamic parameters such as: Ea, DeltaH(*),
      DeltaS(*) and DeltaG(*) were estimated from the DTG curves. 

PMID- 24682060
TI  - A comparative study of experimental and theoretical results of conformations of
      oxovanadium(IV) complexes with 4-acyl pyrazolone ligands using DFT method.
AB  - The optimized structures and electronic properties of the oxovanadium(IV)
      complexes containing 4-acyl pyrazolone ligands were calculated using density
      functional theory. The total energies of both the complexes were calculated e.g.
      syn and anti conformation of complex 1 and complex 2 with and without solvent.
      The calculated total energy for syn conformation was -10.162 keV, while total
      energy for anti conformation was -10.155 keV. Similarly, the calculated total
      energy for complex 2 with solvent was obtained -10.793 keV, while total energy
      for complex 2 without solvent was -10.158 keV. The total energy calculation shows
      that syn conformation is more stable in complex 1, while complex 2 is more stable
      in twisted geometry with solvent. In order to investigate the electronic
      properties of ligands and complexes, quantum chemical parameters, such as the
      highest occupied molecular orbital energy (HOMO), the lowest unoccupied molecular
      orbital energy (LUMO), and energy gap were calculated. The theoretically
      calculated data of the complexes are in good agreement with the data obtained by
      the single-crystal X-ray diffraction analysis.

PMID- 24682061
TI  - New aromatic/heteroaromatic propanesulfonylhydrazone compounds: synthesis,
      physical properties and inhibition studies against carbonic anhydrase II (CAII)
      enzyme.
AB  - Some new aromatic/heteroaromatic propanesulfonylhydrazone derivatives (1-8) were
      synthesized and characterized by elemental analyses, FT-IR, (1)H NMR, (13)C NMR,
      LC/MS techniques. The geometry optimizations and spectral calculations were
      performed by using DFT/B3LYP/6-311G(d,p) basis set in Gaussian 09 program. The
      inhibition activities of the synthesized compounds on carbonic anhydrase II
      (CAII) isoenzyme have been investigated by comparing IC50 values. Acetazolamide
      (5-acetamido-1,3,4-thiadiazole-2-sulfonamide) AAZ, a clinically used in CAII
      inhibition has also been investigated as standard inhibitor. The best
      aromatic/heteroaromatic propanesulfonylhydrazone inhibitors of this isoform were
      o-aminobenzaldehydepropanesulfonylhydrazone (1) and thiophenecarboxyaldehyde
      propanesulfonylhydrazone (5) having the same IC50 (0.55 mM) value. The molecular
      descriptors for propanesulfonylhydrazones were obtained to develop structure
      activity relationship (SAR) model between experimental IC50 values and the
      molecular descriptors calculated by PM3-based SAR models in Hyperchem 8,
      respectively. The obtained models confirm the good carbonic anhydrase II (CAII)
      inhibition activity of the propanesulfonylhydrazone derivatives. The selected
      descriptors are sensitive both to the imine (CH=N) and NH2 groups that are
      responsible from higher activities of (1) and (5) in their series.

PMID- 24682062
TI  - TDDFT study of UV-vis spectra of permethrin, cypermethrin and their beta
      cyclodextrin inclusion complexes: a comparison of dispersion correction DFT (DFT
      D3) and DFT.
AB  - A comparative study of DFT and DFT-D3 has been carried out on the UV-vis
      absorption of permethrin, cypermethrin and their beta-cyclodextrin inclusion
      complexes. The TDDFT method with PCM (or COSMO) model was adopted and B3LYP, BLYP
      and BLYP-D3 functionals were selected. Comparing the simulated spectra with
      experimental one, we can notice that pure BLYP functional can better reproduce
      the UV-vis spectra than hybrid B3LYP, but empirical dispersion corrections BLYP
      D3 has better performance than BLYP. BLYP-D3 calculations reveal that the main
      absorption bands of permethrin and cypermethrin arise from the pi->pi(*)
      transition, after encapsulated by beta-CD to form inclusion complexes, the host
      guest intermolecular charge transfer (ICT) makes the main absorption bands to be
      changed significantly in wavelength and intensity. 

PMID- 24682063
TI  - TiO2 nanoparticles versus TiO2-SiO2 nanocomposites: a comparative study of photo
      catalysis on acid red 88.
AB  - A novel, simple, less time-consuming and cost-effective wet chemical technique
      was used to synthesis TiO2 nanoparticles and TiO2-SiO2 nanocomposites using
      Titanium tetra isopropoxide (TTIP) as a precursor relatively at low temperature
      in acidic pH. Titania sol was prepared by hydrolysis of TTIP and was mixed with
      silicic acid and tetrahydrofuran mixture. The reaction was carried out under
      vigorous stirring for 6h and dried at room temperature. The resulting powders
      were characterized by UV-Visible spectroscopy, Fourier transform infrared (FT
      IR), X-ray diffraction, scanning electron microscope (SEM) and transmission
      electron microscope (TEM). The grain size of the particles was calculated by X
      ray diffraction, surface morphology and chemical composition was determined from
      scanning electron microscopy-energy dispersive spectroscopy, metal oxide
      stretching was confirmed from FT-IR spectroscopy, band gap was calculated using
      UV-Visible spectroscopy. Surface area of the composite as calculated by BET
      analyzer and it was found to be 65 and 75 m(2)/g for TiO2 and TiO2-SiO2
      respectively. The photocatalytic experiments were performed with aqueous solution
      of acid red 88 with TiO2 and TiO2-SiO2 batch studies for 4h irradiation, direct
      photolysis of TiO2 and TiO2-SiO2 contributed 94.2% and 96.5% decomposition in
      solar radiation for the optimized concentration of acid red 88.

PMID- 24682064
TI  - A dansyl-rhodamine chemosensor for Fe(III) based on off-on FRET.
AB  - A novel fluorescent chemosensor bearing a rhodamine and a dansyl moiety was
      developed for highly selective detection of Fe(3+) based on fluorescence
      resonance energy transfer (FRET) mechanism. Binding of Fe(3+) to the chemosensor
      induced spirolactam ring opening in the rhodamine moiety and subsequent off-on
      FRET from the dansyl energy donor to the rhodamine energy acceptor due to the
      spectral overlap between the emission of the dansyl moiety and the absorption of
      the ring opened rhodamine moiety. Job's plot analysis indicated a 1:1 binding
      stoichiometry between the chemosensor and Fe(3+). The association constant was
      estimated to be 2.72*10(3) M(-1) according to the Benesi-Hildebrand method. With
      the feature of easy synthesis, simple structural skeleton and excellent sensing
      ability, the newly synthesized chemosensor provided the potential for applying as
      a highly selective fluorescent probe in complex samples containing various
      competitive metal ions and developing other metal ion chemosensors to fulfill
      various needs of biological and environmental field.

PMID- 24682065
TI  - A study of the phase transition of reheated diphenyl carbazide (DPC) by using UV
      spectroscopy.
AB  - Phase transition phenomenon in reheated diphenyl carbazide (DPC) is studied here
      using UV spectroscopy. The optical band gap for reheated DPC is obtained by
      measuring the optical diffused reflectance (DR) and equals to 3.55 eV. Also, the
      optical band gap is calculated using UV technique and equals to 3.548 eV. The
      absorbance of reheated DPC is studied at some selected temperatures in order to
      check the presence of phase transitions at 90 degrees C and 125 degrees C.
      According to the present work, the band gaps are calculated at 80 degrees C, 110
      degrees C and 130 degrees C and equal to 3.548 eV. But at 100 degrees C, the
      optical band gap has changed to 4.139 eV. It was found that each phase of
      reheated DPC belongs to a certain definite crystal structure. The presence of the
      phase transitions are checked and confirmed by scanning electron microscopy
      (SEM). The structural properties and morphology of reheated diphenyl carbazide
      are investigated by SEM. The SEM images are taken at some selected temperatures
      to confirm the presence of phase transitions.

PMID- 24682066
TI  - Indium-chlorine and gallium-chlorine tetrasubstituted phthalocyanines in a bulk
      system, Langmuir monolayers and Langmuir-Blodgett nanolayers--spectroscopic
      investigations.
AB  - The paper deals with spectroscopic characterization of metallic phthalocyanines
      (Pc's) (indium and gallium) complexed with chlorine and substituted with four
      benzyloxyphenoxy peripheral groups in bulk systems, 2D Langmuir monolayers and
      Langmuir-Blodgett nanolayers. An influence of the molecular structure of dyes
      (the presence of metal and of substitutes attached to the phthalocyanine
      macroring) on the in situ measurements of light absorption is reported. Molecular
      arrangement of the phthalocyanine molecular skeleton in the Langmuir monolayers
      on water substrate and in the Langmuir-Blodgett nanolayers is evaluated. A
      comparison of the light absorption spectra of the phthalocyanine monolayers with
      the spectra of the dyes in solution supports the existence of dye aggregates in
      the monolayer. It was shown that the type of dye aggregates (oblique and H types)
      depends markedly on the dye molecular structures. The NIR-IR, IR reflection
      absorption and Raman spectra are also monitored for Langmuir-Blodgett nanolayers
      in non-polarized and polarized light. It was shown that the dye molecules in the
      Langmuir-Blodgett layers are oriented nearly vertically with respect to a gold
      substrate. 

PMID- 24682067
TI  - Genomics of sex determination.
AB  - Sex determination is a major switch in the evolutionary history of angiosperm,
      resulting 11% monoecious and dioecious species. The genomic sequences of papaya
      sex chromosomes unveiled the molecular basis of recombination suppression in the
      sex determination region, and candidate genes for sex determination.
      Identification and analyses of sex determination genes in cucurbits and maize
      demonstrated conservation of sex determination mechanism in one lineage and
      divergence between the two systems. Epigenetic control and hormonal influence of
      sex determination were elucidated in both plants and animals. Intensive
      investigation of potential sex determination genes in model species will improve
      our understanding of sex determination gene network. Such network will in turn
      accelerate the identification of sex determination genes in dioecious species
      with sex chromosomes, which are burdensome due to no recombination in sex
      determining regions. The sex determination genes in dioecious species are crucial
      for understanding the origin of dioecy and sex chromosomes, particularly in their
      early stage of evolution. 

PMID- 24682068
TI  - Invited editorial for special issue on affective disorders.

PMID- 24682070
TI  - Transboundary smoke haze pollution in Malaysia: inpatient health impacts and
      economic valuation.
AB  - This study assessed the economic value of health impacts of transboundary smoke
      haze pollution in Kuala Lumpur and adjacent areas in the state of Selangor,
      Malaysia. Daily inpatient data from 2005, 2006, 2008, and 2009 for 14 haze
      related illnesses were collected from four hospitals. On average, there were 19
      hazy days each year during which the air pollution levels were within the Lower
      Moderate to Hazardous categories. No seasonal variation in inpatient cases was
      observed. A smoke haze occurrence was associated with an increase in inpatient
      cases by 2.4 per 10,000 populations each year, representing an increase of 31
      percent from normal days. The average annual economic loss due to the inpatient
      health impact of haze was valued at MYR273,000 ($91,000 USD). 

PMID- 24682071
TI  - Metal composition of fine particulate air pollution and acute changes in
      cardiorespiratory physiology.
AB  - BACKGROUND: Studying the physiologic effects of components of fine particulate
      mass (PM2.5) could contribute to a better understanding of the nature of toxicity
      of air pollution. OBJECTIVES: We examined the relation between acute changes in
      cardiovascular and respiratory function, and PM2.5-associated-metals. METHODS:
      Using generalized linear mixed models, daily changes in ambient PM2.5-associated
      metals were compared to daily changes in physiologic measures in 59 healthy
      subjects who spent 5-days near a steel plant and 5-days on a college campus.
      RESULTS: Interquartile increases in calcium, cadmium, lead, strontium, tin,
      vanadium and zinc were associated with statistically significant increases in
      heart rate of 1-3 beats per minute, increases of 1-3 mmHg in blood pressure
      and/or lung function decreases of up to 4% for total lung capacity. CONCLUSION:
      Metals contained in PM2.5 were found to be associated with acute changes in
      cardiovascular and respiratory physiology.

PMID- 24682072
TI  - Relating metal bioavailability to risk assessment for aquatic species: Daliao
      River watershed, China.
AB  - The spatial distribution of metal bioavailability (Ni, Cu, Zn, and Pb) was first
      evaluated within the waters of Daliao River watershed, using the diffusive
      gradient in thin films (DGT) and chemical equilibrium models. To assess potential
      risks associated with metal bioavailability, site-specific 95% protection levels
      (HC5), risk characterizations ratios (RCR) and ratios of DGT-labile/HC5 were
      derived, using species sensitivity distribution (SSD). The highest
      bioavailability values for metals were recorded in the main channel of the Daliao
      River, followed by the Taizi River. Dynamic concentrations predicted by WHAM 7.0
      and NICA-Donnan for Cu and Zn agreed well with DGT results. The estuary of the
      Daliao River was found to have the highest risks related to Ni, Cu, and Zn. The
      number of sites at risk increased when considering the total toxicity of Ni, Cu,
      and Zn. 

PMID- 24682073
TI  - Lead and other elements in house dust of Japanese residences--source of lead and
      health risks due to metal exposure.
AB  - The levels of 25 elements in house dust collected from 100 general Japanese
      residences were measured. Factor analysis was applied on the multi-element data
      to explore source of Pb (median concentration 49.1 mg/kg) in house dust. Six
      factors were extracted and Pb was found to have great loading on the fifth factor
      with Sb and Sn, suggesting solder (Sn), and plastic and metals (Sb) may be the
      sources of Pb in the house dust of Japanese residences. No significant loading
      was found on soil-related factors indicating non-significant contribution of Pb
      in track-in soil. Seven heavy metals (Cd, Cu, Mo, Pb, Sb, Sn, and Zn) were found
      in house dust at >10 times more condensed than crustal abundance. Health risk of
      these elements to children via the ingestion of house dust was estimated based on
      the comparison with tolerable daily intake and found to be non-significant for
      most of the elements.

PMID- 24682074
TI  - The impact of gypsum mine water: a case study on morphology and DNA integrity in
      the freshwater invertebrate, Gammarus balcanicus.
AB  - The aim of our study was to investigate how exposure to heavy metal-rich waters
      from gypsum mining affects the morphology and levels of primary DNA damage in
      Gammarus balcanicus. Chemical analysis revealed increased concentrations of
      metals in water and sediment collected at a site impacted by gypsum mine
      wastewaters. The specimens also showed elevated total tissue metal levels when
      compared with the organisms collected at the reference site. The most prominent
      increase was observed for strontium, followed by iron, nickel, vanadium,
      aluminium, and manganese. The major pathway of entry for these toxic substances
      was through the degraded exoskeleton as a consequence of excessive strontium
      input (unbalanced calcium/strontium ratio) and altered permeability. Disturbed
      exoskeleton integrity was observed only in individuals collected downstream of
      the gypsum mine, which was confirmed by electron microscopy. Levels of primary
      DNA damage were evaluated using the alkaline comet assay in the haemolymph of the
      specimens. 

PMID- 24682075
TI  - High-throughput sequencing and de novo assembly of Brassica oleracea var.
      Capitata L. for transcriptome analysis.
AB  - BACKGROUND: The cabbage, Brassica oleracea var. capitata L., has a
      distinguishable phenotype within the genus Brassica. Despite the economic and
      genetic importance of cabbage, there is little genomic data for cabbage, and most
      studies of Brassica are focused on other species or other B. oleracea subspecies.
      The lack of genomic data for cabbage, a non-model organism, hinders research on
      its molecular biology. Hence, the construction of reliable transcriptomic data
      based on high-throughput sequencing technologies is needed to enhance our
      understanding of cabbage and provide genomic information for future work.
      METHODOLOGY/PRINCIPAL FINDINGS: We constructed cDNAs from total RNA isolated from
      the roots, leaves, flowers, seedlings, and calcium-limited seedling tissues of
      two cabbage genotypes: 102043 and 107140. We sequenced a total of six different
      samples using the Illumina HiSeq platform, producing 40.5 Gbp of sequence data
      comprising 401,454,986 short reads. We assembled 205,046 transcripts (>= 200 bp)
      using the Velvet and Oases assembler and predicted 53,562 loci from the
      transcripts. We annotated 35,274 of the loci with 55,916 plant peptides in the
      Phytozome database. The average length of the annotated loci was 1,419 bp. We
      confirmed the reliability of the sequencing assembly using reverse-transcriptase
      PCR to identify tissue-specific gene candidates among the annotated loci.
      CONCLUSION: Our study provides valuable transcriptome sequence data for B.
      oleracea var. capitata L., offering a new resource for studying B. oleracea and
      closely related species. Our transcriptomic sequences will enhance the quality of
      gene annotation and functional analysis of the cabbage genome and serve as a
      material basis for future genomic research on cabbage. The sequencing data from
      this study can be used to develop molecular markers and to identify the extreme
      differences among the phenotypes of different species in the genus Brassica.

PMID- 24682076
TI  - The regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung
      tumor promotion by estradiol in female A/J mice.
AB  - Epidemiological studies indicate that women are at a higher risk developing lung
      cancer than men are. It is suggested that estrogen is one of the most important
      factors in lung cancer development in females. Additionally, cigarette smoke, and
      environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may
      play salient roles in female lung carcinogenesis. However, the mechanisms
      responsible for the interaction of these factors in the promotion of lung cancer
      are still poorly understood. The present study was designed to explore two ideas:
      first, the synergistic lung tumorigenic effects of 4-(methylnitrosamino)-1-(3
      pyridyl)-butanol (NNK) combined with TCDD, 17beta-estradiol (E2) or both through
      a long-term treatment experiment, and second, to identify early changes in the
      inflammatory and signaling pathways through short-term treatment experiments. The
      results indicate that A/J mice given E2 had strong effects in potentiating NNK
      induced activation of MAPK signaling, NFkappaB, and COX-2 expression. In the long
      term exposure model, E2 had a strong tumor promoting effect, whereas TCDD
      antagonized this effect in A/J mice. We conclude that treatment with NNK combined
      with either E2 or TCDD induces lung carcinogenesis and the promotion effects
      could be correlated with lung inflammation. E2 was shown to potentiate NNK
      induced inflammation, cell proliferation, thereby leading to lung tumorigenesis. 

PMID- 24682077
TI  - Alignment-free visualization of metagenomic data by nonlinear dimension
      reduction.
AB  - The visualization of metagenomic data, especially without prior taxonomic
      identification of reconstructed genomic fragments, is a challenging problem in
      computational biology. An ideal visualization method should, among others, enable
      clear distinction of congruent groups of sequences of closely related taxa, be
      applicable to fragments of lengths typically achievable following assembly, and
      allow the efficient analysis of the growing amounts of community genomic sequence
      data. Here, we report a scalable approach for the visualization of metagenomic
      data that is based on nonlinear dimension reduction via Barnes-Hut Stochastic
      Neighbor Embedding of centered log-ratio transformed oligonucleotide signatures
      extracted from assembled genomic sequence fragments. The approach allows for
      alignment-free assessment of the data-inherent taxonomic structure, and it can
      potentially facilitate the downstream binning of genomic fragments into uniform
      clusters reflecting organismal origin. We demonstrate the performance of our
      approach by visualizing community genomic sequence data from simulated as well as
      groundwater, human-derived and marine microbial communities. 

PMID- 24682078
TI  - Convulsions in 2 patients after bilateral ultrasound-guided transversus abdominis
      plane blocks for cesarean analgesia.
AB  - OBJECTIVE: Transversus abdominis plane (TAP) block is commonly used for
      postcesarean section analgesia and compares favorably with other systemic and
      regional analgesia techniques. No major complications of ultrasound-guided TAP
      block have previously been reported in this indication. We report 2 cases of
      systemic local anesthetic toxicity in this context leading to seizures and
      treated with lipid emulsion. CASE REPORT: The first event occurred 10 minutes
      after ultrasound-guided bilateral injections, each consisting of 20 mL of
      levobupivacaine 3.75 mg/mL. Two episodes of tonic-clonic seizure required
      resuscitation measures and 200 mL of lipid emulsion. The second case 25 minutes
      after a 20-mL bilateral injection of ropivacaine 7.5 mg/mL. One generalized tonic
      clonic seizure required bag-mask ventilation and 250 mL of lipid emulsion. In
      both cases, patients were successfully treated and fully recovered. CONCLUSIONS:
      These cases cast a cautionary note for the use of TAP blocks after cesarean
      delivery. The risk of systemic local anesthetic toxicity after this procedure
      remains unknown in this population and plasma concentration of local anesthetics
      should be measured in case of suspected toxicity. To limit this risk, a low
      concentration of local anesthetic solution should be chosen when a "20 mL
      bilaterally" regimen is necessary to achieve the required spread for a successful
      block.

PMID- 24682079
TI  - A prospective randomized observer-blinded study to assess postoperative analgesia
      provided by an ultrasound-guided bilateral thoracic paravertebral block for
      children undergoing the Nuss procedure.
AB  - BACKGROUND AND OBJECTIVES: This prospective, randomized, single-blinded study
      evaluates the effectiveness of the ultrasound-guided bilateral thoracic
      paravertebral (BTPV) block for providing postoperative pain control in children
      undergoing the Nuss procedure. METHODS: Thirty American Society of
      Anesthesiologists I-II children with pectus excavatum, scheduled for the Nuss
      procedure, were enrolled at West China Hospital of Sichuan University. The
      patients were randomly allocated into the BTPV block group or the control group.
      In the BTPV group, 0.25% ropivacaine 0.5 mL/kg with 1:200,000 epinephrine was
      injected under ultrasound guidance on each side at the level of the fifth
      thoracic vertebra. Postoperative pain was evaluated in both groups for the first
      48 hours. Total opioid administered and cumulative attempts on the patient/parent
      controlled intravenous analgesia (PCA) pump were recorded. Postoperative negative
      behavioral changes in the children were evaluated on postoperative days 1, 7, and
      30, respectively, using the posthospital behavior questionnaire. RESULTS: The
      pain scores were significantly reduced in the postanesthesia care unit and for
      the first 48 hours postoperatively in the BTPV group compared to the control
      group (P < 0.01). The sufentanil use in the postanesthesia care unit was
      significantly greater in the control group [mean (SD), 0.2 (0) mcg/kg] compared
      to the BTPV group [mean (SD), 0.05 (0.06) mcg/kg] (P < 0.01). The postoperative
      sufentanil use was significantly higher in the control group during the first 24
      hours (P < 0.01). Numbers of attempts on the PCA pump were significantly greater
      in the control group (P < 0.01). The posthospital behavior questionnaire score
      was lower in the BTPV group on day 1, day 7, and 1 month, respectively (P <
      0.01). CONCLUSIONS: Ultrasound-guided BTPV block provides improved postoperative
      analgesia for children undergoing the Nuss procedure as compared with intravenous
      PCA and decreases the incidence of postoperative behavioral disturbance.

PMID- 24682080
TI  - Continuous versus single-injection sciatic nerve block added to continuous
      femoral nerve block for analgesia after total knee arthroplasty: a prospective,
      randomized, double-blind study.
AB  - BACKGROUND AND OBJECTIVES: The benefit of adding sciatic nerve block (SNB) to
      femoral nerve block to improve analgesia after total knee arthroplasty (TKA) is
      uncertain. We hypothesized that the effective duration of single-injection SNB is
      too short to improve postoperative analgesia and that this contributes to
      conflicting results on the efficacy of SNB after TKA. We evaluated this
      hypothesis in a prospective double-blind randomized controlled trial. METHODS:
      Sixty patients undergoing TKA were randomly allocated to a continuous SNB group
      or a single-injection SNB group. All patients received femoral nerve block (0.5%
      ropivacaine 20 mL) and SNB (0.2% ropivacaine 20 mL) and catheters were inserted
      into both peripheral nerve block sites before surgery. Both groups received
      continuous femoral nerve block and patient-controlled intravenous analgesia with
      morphine. Continuous SNB (0.2% ropivacaine 5 mL/h; continuous SNB group) or sham
      continuous SNB (0.9% normal saline 5 mL/h; single-injection SNB group) was
      provided after surgery. The primary outcome was total morphine consumption for 48
      hours after surgery. RESULTS: Total morphine consumption in the 48-hour period
      after surgery was significantly lower in the continuous SNB group compared with
      the single-injection SNB group [4.9 (5.9) vs 9.7 (9.5) mg, P = 0.002]. Visual
      analog scale pain scores at rest were also significantly lower in the continuous
      SNB group (P = 0.035). CONCLUSIONS: The combination of continuous femoral and SNB
      provides a superior opioid sparing effect and improves analgesia after TKA.

PMID- 24682082
TI  - Off side! A simple modification to the parasagittal in-plane approach for
      paravertebral block.
AB  - The use of thoracic paravertebral blocks (PVBs) for breast cancer surgery confers
      important analgesic benefits. Several ultrasound (US)-guided PVB approaches have
      been described, but still elusive is the ideal technique that (1) permits
      continuous visualization of the entire needle shaft and tip, (2) avoids aiming
      the needle tip and injectate directly toward the neuraxis, and (3) is easy to
      perform. Although the parasagittal view in-plane PVB approach satisfies the
      former 2 criteria, maneuvering the needle to reach the targeted paravertebral
      space can be difficult as its trajectory is often obstructed by the bony
      transverse processes. This brief technical report describes the "off-side"
      technique--a simple solution to the technical challenge posed by the double
      fulcrum effect exerted first by the transducer and then by the adjacent inferior
      transverse process. Our "off-side" technique marks a departure from conventional
      US-guided regional anesthesia teaching that recommends positioning the target in
      the middle of the US field and may be useful in similar types of US-guided
      regional anesthesia procedures such as neuraxial blockade.

PMID- 24682081
TI  - Relationship between endogenous opioid function and opioid analgesic adverse
      effects.
AB  - BACKGROUND AND OBJECTIVES: Our recent work indicates that endogenous opioid
      activity influences analgesic responses to opioid medications. This secondary
      analysis evaluated whether endogenous opioid activity is associated with degree
      of opioid analgesic adverse effects, and whether chronic pain status and sex
      affect these adverse effects. METHODS: Using a double-blind, randomized, placebo
      controlled, crossover design, 51 subjects with chronic low back pain and 38
      healthy controls participated in 3 separate sessions, undergoing 2 laboratory
      evoked pain tasks (ischemic and thermal) after receiving placebo, naloxone, or
      morphine. Endogenous opioid system function was indexed by the difference in pain
      responses between the placebo and naloxone conditions. These measures were
      examined for associations with morphine-related adverse effects. RESULTS: Chronic
      pain subjects reported significantly greater itching and unpleasant bodily
      sensations with morphine than controls (P < 0.05). Across groups, only 6 of 112
      possible associations between adverse effects and blockade effects were
      significant. For the ischemic task, higher endogenous opioid function was
      associated with greater itching (visual analog scale [VAS]; P < 0.05), numbness
      (tolerance; P < 0.001), dry mouth (tolerance; P < 0.05), and unpleasant bodily
      sensations (VAS; P < 0.05). For the thermal task, higher endogenous opioid
      function was associated with greater numbness (VAS; P < 0.05) and feeling
      carefree (VAS; P < 0.05). There were no significant main or interaction effects
      of chronic pain status or sex on these findings. CONCLUSIONS: No consistent
      relationships were observed between endogenous opioid function and morphine
      related adverse effects. This is in stark contrast to our previous observation of
      strong relationships between elevated endogenous opioid function and smaller
      morphine analgesic effects.

PMID- 24682083
TI  - Anesthesia, outcomes, and public health: changing health care while "asleep".
AB  - More than 50 million surgical procedures are performed annually in the United
      States, with perioperative complications and related long-term adverse outcomes
      profoundly affecting the nation's health. A growing number of studies recognize
      that type of anesthesia, a main determinant of perioperative care, is associated
      with perioperative morbidity and mortality. Emerging data suggest, for example,
      that anesthesia may be a determinant of cancer recurrence after surgery. Further
      research is needed to elucidate the impact of anesthesia-related factors on short
      and long-term health outcomes. Progress in this area of medicine and its public
      health consequences will depend largely on the interest of the public,
      researchers, and health care policy makers. 

PMID- 24682085
TI  - Antitumor activity of combination treatment with gefitinib and docetaxel in EGFR
      TKI-sensitive, primary resistant and acquired resistant human non-small cell lung
      cancer cells.
AB  - In a number of large clinical studies, concurrent administration of the epidermal
      growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with cytotoxic
      chemotherapy has failed to improve the survival rate in unselected patients with
      advanced non-small cell lung cancer (NSCLC). The purpose of the current study was
      to investigate the antitumor effects of gefitinib in combination with docetaxel
      in EGFR-TKI-sensitive, primary resistant and acquired resistant human lung cancer
      cell lines and the associated molecular mechanisms. EGFR-TKI-sensitive and EGFR
      TKI-resistant human lung cancer cell lines were exposed to gefitinib or docetaxel
      alone, or in combination. Cell viability was assessed using the MTT assay. Cell
      cycle distribution and apoptosis were measured by flow cytometry and alterations
      in signaling pathways were examined by immunoblotting. The cytotoxic interaction
      between docetaxel and gefitinib was determined by combination index (CI)
      analysis. Coadministration of gefitinib and docetaxel was observed to result in
      superior inhibition of tumor cell proliferation, however, increased rates of
      apoptosis were only observed in EGFR-TKI-sensitive cells, whereas, antagonistic
      activity was observed in the EGFR-TKI-resistant cell lines. Gefitinib arrested
      the cell cycle at the G1 phase, whereas docetaxel arrested the cell cycle at the
      S phase. In addition, in cells exhibiting a synergistic interaction between
      gefitinib and docetaxel, an increase in p-EGFR and p-AKT was observed following
      chemotherapy exposure. By contrast, in cells exhibiting no change or a decrease
      in p-EGFR and p-AKT following docetaxel treatment, an antagonistic interaction
      between the two agents was observed. In conclusion, the combination of docetaxel
      and gefitinib generated synergistic effects in EGFR-TKI-sensitive cells and
      antagonistic effects in EGFR-TKI-primary and acquired resistant cells, suggesting
      that EGFR-TKIs, combined with docetaxel, may be beneficial to NSCLC patients with
      EGFR mutations. The results also indicate that the interactions between gefitinib
      and docetaxel may be associated with the effect of docetaxel on EGFR
      phosphorylation.

PMID- 24682084
TI  - Arabidopsis transcriptome analysis reveals key roles of melatonin in plant
      defense systems.
AB  - Melatonin is a ubiquitous molecule and exists across kingdoms including plant
      species. Studies on melatonin in plants have mainly focused on its physiological
      influence on growth and development, and on its biosynthesis. Much less attention
      has been drawn to its affect on genome-wide gene expression. To comprehensively
      investigate the role(s) of melatonin at the genomics level, we utilized mRNA-seq
      technology to analyze Arabidopsis plants subjected to a 16-hour 100 pM (low) and
      1 mM (high) melatonin treatment. The expression profiles were analyzed to
      identify differentially expressed genes. 100 pM melatonin treatment significantly
      affected the expression of only 81 genes with 51 down-regulated and 30 up
      regulated. However, 1 mM melatonin significantly altered 1308 genes with 566 up
      regulated and 742 down-regulated. Not all genes altered by low melatonin were
      affected by high melatonin, indicating different roles of melatonin in regulation
      of plant growth and development under low and high concentrations. Furthermore, a
      large number of genes altered by melatonin were involved in plant stress defense.
      Transcript levels for many stress receptors, kinases, and stress-associated
      calcium signals were up-regulated. The majority of transcription factors
      identified were also involved in plant stress defense. Additionally, most
      identified genes in ABA, ET, SA and JA pathways were up-regulated, while genes
      pertaining to auxin responses and signaling, peroxidases, and those associated
      with cell wall synthesis and modifications were mostly down-regulated. Our
      results indicate critical roles of melatonin in plant defense against various
      environmental stresses, and provide a framework for functional analysis of genes
      in melatonin-mediated signaling pathways. 

PMID- 24682086
TI  - The cost of fear: avoidant decision making in a spider gambling task.
AB  - Individuals with anxiety disorders typically avoid fear-relevant stimuli even if
      they miss potential rewards. However, few studies have accounted for such costs
      of fear-related avoidance in doing so. In this study, 51 spider fearful and 49
      non-fearful participants completed the Spider Gambling Task, our modification of
      the Iowa Gambling Task, to investigate whether fear-relevant stimuli trigger
      avoidant decisions in the presence of potential rewards. In one version,
      advantageous choices were associated with pictures of spiders, whereas the same
      pictures were associated with disadvantageous choices in another version. Fearful
      participants generally avoided choices associated with pictures of spiders, which
      resulted in lower overall gains in the version with advantageous spider decks.
      Although this relative avoidance was sustained, fearful participants
      progressively approach more advantageous spider choices. These findings
      demonstrate that phobic fear results in irrational avoidant decisions which can
      result in considerable cost. Potential long-term rewards for approach may,
      however, diminish absolute avoidance behavior.

PMID- 24682069
TI  - Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in
      patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial.
AB  - IMPORTANCE: No therapy directed against diabetes has been shown to unequivocally
      reduce the excess risk of cardiovascular complications. Aleglitazar is a dual
      agonist of peroxisome proliferator-activated receptors with insulin-sensitizing
      and glucose-lowering actions and favorable effects on lipid profiles. OBJECTIVE:
      To determine whether the addition of aleglitazar to standard medical therapy
      reduces cardiovascular morbidity and mortality among patients with type 2
      diabetes mellitus and a recent acute coronary syndrome (ACS). DESIGN, SETTING,
      AND PARTICIPANTS: AleCardio was a phase 3, multicenter, randomized, double-blind,
      placebo-controlled trial conducted in 720 hospitals in 26 countries throughout
      North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of
      7226 patients hospitalized for ACS (myocardial infarction or unstable angina)
      with type 2 diabetes occurred between February 2010 and May 2012; treatment was
      planned to continue until patients were followed-up for at least 2.5 years and
      950 primary end point events were positively adjudicated. INTERVENTIONS:
      Randomized in a 1:1 ratio to receive aleglitazar 150 ug or placebo daily. MAIN
      OUTCOMES AND MEASURES: The primary efficacy end point was time to cardiovascular
      death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end
      points were hospitalization due to heart failure and changes in renal function.
      RESULTS: The trial was terminated on July 2, 2013, after a median follow-up of
      104 weeks, upon recommendation of the data and safety monitoring board due to
      futility for efficacy at an unplanned interim analysis and increased rates of
      safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of
      patients withdrew consent. The primary end point occurred in 344 patients (9.5%)
      in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard
      ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events,
      including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14),
      gastrointestinal hemorrhages (2.4% for aleglitazar vs 1.7% for placebo, P = .03),
      and renal dysfunction (7.4% for aleglitazar vs 2.7% for placebo, P < .001) were
      increased. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes and
      recent ACS, use of aleglitazar did not reduce the risk of cardiovascular
      outcomes. These findings do not support the use of aleglitazar in this setting
      with a goal of reducing cardiovascular risk. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01042769.

PMID- 24682087
TI  - The role of alpha-1 and alpha-2 adrenoceptors in restraint stress-induced liver
      injury in mice.
AB  - Acute stress affects cellular integrity in many tissues including the liver, but
      its underlying mechanism is still unclear. The aim of the present study was to
      investigate the potential involvement of catecholamines and adrenoceptors in the
      regulation of acute restraint stress-induced liver injury. Restraint was achieved
      by placing mice in restraint tubes. Mice were treated with either an alpha-l
      antagonist, prazosin, an alpha-2 antagonist, yohimbine, a beta-l antagonist,
      betaxolol, a beta-2 antagonist, ICI 118551, or a central and peripheral
      catecholamine depleting agent, reserpine, and followed by restraint stress.
      Assessment of liver injury (serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) , hepatic total GSH, GSSG and GSH/GSSG ratio) ,
      histopathology and of apoptosis, by TUNEL (terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labelling) assay and western blotting, was performed.
      Three hours of restraint stress resulted in liver injury, as indexed by elevated
      serum transaminase levels, decreased hepatic total GSH levels and GSH/GSSG ratio,
      increased hepatic GSSG levels as well as enhanced hepatocytes apoptosis. Either
      reserpine or prazosin or yohimbine was found to attenuate liver injury.
      Furthermore, prazosin and yohimbine protected against restraint-induced
      hepatocytes apoptosis through attenuating the activation of caspases-9 and -3 and
      reducing the Bax/Bcl-2 ratio. These results suggest that alpha-1 and alpha-2
      adrenoceptors mediate restraint-induced liver oxidative injury through caspase-9
      and Bcl-2 family of apoptotic regulatory proteins. 

PMID- 24682089
TI  - [Fiber optic endoscopic evaluation of swallowing on the stroke unit.]

PMID- 24682090
TI  - sp(3)C-H bond alkylation of ketones with alkenes via ruthenium(II) catalysed
      dehydrogenation of alcohols.
AB  - The sp(3)C-H bond functionalisation of 2-pyridyl ethanols upon reaction with
      alkenes, in the presence of a [RuCl2(arene)]2 catalyst and Cu(OAc)2.H2O, is
      performed under mild conditions without additional base. This reaction proceeds
      via a tandem alcohol dehydrogenation/alkylation with alkenes of the resulting
      ketone at its alpha sp(3)C-H bond. 

PMID- 24682091
TI  - Intake of fruit juice and incidence of type 2 diabetes: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Several prospective studies have been conducted to examine the
      relationship between fruit juice intake and risk of incident type 2 diabetes, but
      results have been mixed. In the present study, we aimed to estimate the
      association between fruit juice intake and risk of type 2 diabetes. METHODS:
      PubMed and Embase databases were searched up to December 2013. All prospective
      cohort studies of fruit juice intake with risk of type 2 diabetes were included.
      The pooled relative risks (RRs) with 95% confidence intervals (CIs) for highest
      vs. lowest category of fruit juice intake were estimated using a random-effects
      model. RESULTS: A total of four studies (191,686 participants, including 12,375
      with type 2 diabetes) investigated the association between sugar-sweetened fruit
      juice and risk of incident type 2 diabetes, and four studies (137,663
      participants and 4,906 cases) investigated the association between 100% fruit
      juice and risk of incident type 2 diabetes. A higher intake of sugar-sweetened
      fruit juice was significantly associated with risk of type 2 diabetes (RR = 1.28,
      95%CI = 1.04-1.59, p = 0.02), while intake of 100% fruit juice was not associated
      with risk of developing type 2 diabetes (RR = 1.03, 95% CI = 0.91-1.18, p =
      0.62). CONCLUSIONS: Our findings support dietary recommendations to limit sugar
      sweetened beverages, such as fruit juice with added sugar, to prevent the
      development of type 2 diabetes.

PMID- 24682088
TI  - The changes of liver stiffness and its associated factors for chronic hepatitis B
      patients with entecavir therapy.
AB  - Liver stiffness measurement (LSM) using transient elastography has been proposed
      to assess liver fibrosis well in various liver diseases. This study was to
      determine the changes of LSM and its associated factors for chronic hepatitis B
      (CHB) patients undergoing Entecavir therapy. Consecutive CHB patients underwent
      Entecavir therapy with two LSMs were enrolled. Patients with aspartate
      transaminase (AST) and/or alanine transaminase ?200 IU/L were excluded. The
      retrospective study enrolled 233 patients including 132 without cirrhosis (group
      1) and 101 with cirrhosis (group 2). The mean values of initial liver stiffness
      were 7.9 and 16.6 kPa for patients in group 1 and group 2, respectively
      (p<0.001). In addition to the decline of transaminase levels, there was
      significant reduction of liver stiffness value in a mean interval of 52.8 and
      61.9 weeks between the two LSMs for patients in group 1 and 2, respectively
      (p<0.001). Multivariate analysis showed that higher initial LSM value and
      presence of hepatitis B e-antigen were associated with a greater decline of LSM
      value, whereas follow-up AST?40 IU/L with increased LSM value for group 1
      patients. For group 2 patients, longer interval between the two LSMs, higher
      initial LSM value and AST?40 IU/L were associated with a greater decline of LSM
      value, whereas presence of diabetes mellitus (DM) contributed to increased LSM
      value. In conclusion, CHB patients improved their LSM values after Entecavir
      therapy. Higher initial LSM value contributed to greater LSM reduction. However,
      in cirrhotic patients, DM was associated with an increased LSM value after
      therapy. 

PMID- 24682093
TI  - Antifungal susceptibility of Candida isolates at one institution.
AB  - Species distribution and antifungal susceptibility of Candida isolates at one
      institution were evaluated. Detection rates of fungi were examined for 5 years
      between 2007 and 2011. Sensitivities of fungi to amphotericin B, flucytosine,
      fluconazole, micafungin, itraconazole, and voriconazole were evaluated in blood
      culture-positive patients. A total of 3,832 fungal isolates were detected,
      including Candida albicans 66.5%, Candida glabrata 20.3%, Candida parapsilosis
      6.2%, Candida tropicalis 5.5%, and others 1.5%. Candidemia was diagnosed in 131
      patients, and C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and
      others were present in 42.0%, 27.5%, 16.0%, 8.4%, and 6.1% of these patients,
      respectively. Voriconazole had the lowest MIC90s against C. albicans and C.
      parapsilosis (0.015 and 0.25). Micafungin had a low MIC90 against C. glabrata and
      C. tropicalis. C. albicans was the most common fungus in patients with
      candidemia. Voriconazole and micafungin were effective against C. albicans.
      Amphotericin B was effective for C. parapsilosis, and micafungin showed good
      efficacy against C. glabrata and C. tropicalis. 

PMID- 24682094
TI  - Case of Paecilomyces lilacinus infection occurring in necrotizing fasciitis
      associated skin ulcers on the face and surrounding a tracheotomy stoma.
AB  - A 28-year-old man undergoing treatment for hemophagocytic syndrome developed
      Paecilomyces lilacinus infection in skin ulcers on the face and in the
      tracheotomy stoma. While his bone marrow was suppressed by chemotherapy with
      dexamethasone, cyclosporin and etoposide for hemophagocytic syndrome, dental
      infection led to subacute necrotizing fasciitis caused by Pseudomonas aeruginosa
      on the right side of the face, resulting in a large area of soft tissue defects.
      Etoposide was discontinued, and prophylactic treatment with itraconazole was
      initiated. The ulcers resulting from necrotizing fasciitis were treated
      conservatively using trafermin and alprostadil alfadex ointment 0.003 %, and near
      complete re-epithelialization occurred, except on the right lower eyelid, right
      buccal mucosa and perioral area. However, 6 weeks later, pustules/crusts started
      to form and break down repeatedly, leading to expansion of tissue defects on the
      face. Direct microscopic examination revealed fungal elements, and fungal culture
      identified Paecilomyces lilacinus suspicious twice some other day. Based on DNA
      extraction from the isolated fungus, this fungal strain was identified as
      Paecilomyces lilacinus. Cyclosporin and itraconazole were discontinued, and
      treatment with liposomal amphotericin B and a tapering dose of steroids was
      initiated. Cure was achieved in approximately 2.5 months after treatment
      initiation, and no relapse has been observed. The most important factor that
      ultimately contributed to the resolution of fungal infection might have been
      release of immunosuppression by discontinuing cyclosporin and tapering steroids. 

PMID- 24682092
TI  - The pharmacological rationale for combining muscarinic receptor antagonists and
      beta-adrenoceptor agonists in the treatment of airway and bladder disease.
AB  - Muscarinic receptor antagonists and beta-adrenoceptor agonists are used in the
      treatment of obstructive airway disease and overactive bladder syndrome. Here we
      review the pharmacological rationale for their combination. Muscarinic receptors
      and beta-adrenoceptors are physiological antagonists for smooth muscle tone in
      airways and bladder. Muscarinic agonism may attenuate beta-adrenoceptor-mediated
      relaxation more than other contractile stimuli. Chronic treatment with one drug
      class may regulate expression of the target receptor but also that of the
      opposing receptor. Prejunctional beta2-adrenoceptors can enhance neuronal
      acetylcholine release. Moreover, at least in the airways, muscarinic receptors
      and beta-adrenoceptors are expressed in different locations, indicating that only
      a combined modulation of both systems may cause dilatation along the entire
      bronchial tree. While all of these factors contribute to a rationale for a
      combination of muscarinic receptor antagonists and beta-adrenoceptor agonists,
      the full value of such combination as compared to monotherapy can only be
      determined in clinical studies. 

PMID- 24682095
TI  - Immunohistopathology of Prototheca wickerhamii in cutaneous lesions of
      protothecosis.
AB  - Protothecosis is a rare infection caused by pathogenic algae of the genus
      Prototheca. Prototheca wickerhamii causes cutaneous/subcutaneous opportunistic
      infections in humans and small animals. The diagnosis of protothecosis is based
      on histopathological examination of this organism, which can be confused with
      other fungi and inflammatory cells in infected tissues. In this study,
      immunohistopathological investigation was made of infected cutaneous human and
      animal tissues exhibiting protothecosis using rabbit antiserum against P.
      wickerhamii. Serum detected P. wickerhamii in human and feline protothecosis
      tissues, and did not react with Candida albicans in the human kidney tissues
      showing candidiasis. This antiserum can therefore differentiate P. wickerhamii
      cells from the yeast-like cells of C. albicans and Prototheca zopfii in target
      tissues. 

PMID- 24682096
TI  - Protection of mice from oral Candidiasis by heat-killed enterococcus faecalis,
      possibly through its direct binding to Candida albicans.
AB  - To develop a new therapy against oral candidiasis, a commensal microorganism,
      Enterococcus faecalis was tested for its ability to modulate Candida growth in
      vitro and its therapeutic activities against a murine model in vivo. Addition of
      heat-killed E. faecalis strain EF2001 (EF2001) isolated from healthy human feces
      to the culture of C. albicans strain TIMM1768 inhibited adherence of the latter
      to a microtiter plate in a dose dependent manner and Candida cells surrounded by
      EF2001 were increased. To examine the protective activities of EF2001 in vivo,
      heat-killed EF2001 was applied orally before and after inoculation of Candida to
      the tongue of mice previously immunosuppressed. Two days after inoculation this
      inoculation, both the symptom score and CFU from swabbed-tongue were
      significantly reduced in the EF2001-treated animals. Histological analysis
      indicated that EF2001 may potentiate the accumulation of polymorphnuclear cells
      near a Candida-infected region. These results suggest that oral administration of
      EF2001 has protective activity against oral candidiasis and that the in vivo
      activity may be reflected by direct interaction between EF2001 and Candida cells
      in vitro and the potentiation of an immunostimulatory effect of EF2001. 

PMID- 24682097
TI  - [Basic mycology].

PMID- 24682098
TI  - [Changes in nomenclature on filamentous fungi].

PMID- 24682099
TI  - [Case of the abscess type cutaneous nocardiosis].
AB  - A 58-year-old woman, who had write infull (ITP) and angina, developed a rash
      similar to an insect bite on the left Achilles tendon one week before visiting
      our hospital. The rash evolved into pustule. Three or 4 days later she had
      redness and swelling on her left leg, which was pain full.She went to a clinic,
      where she was given cefdinir (CFDN) and referred to our hospital.When she came to
      our hospital, she had an abscess on her left heel, and linear redness and heat
      along lymph ducts in her left leg and lymph node swelling in her left groin.We
      diagnosed bacterial lymphangitis, and gave her cefcapene (CFPN-PI) and gentamicin
      (GM) ointment. Six days later, she recovered.Later abscess culture yielded an
      organism which was suspected to be Nocardia sp. We identified the organism as
      Nocardia brasiliensis and diagnosed abscess-type cutaneous nocardiosis. We
      administered sulfametthoxazole / trimethoprim for one week and checked her whole
      body on CT, which revealed no lesions.This case was considered to be cutaneous
      nocardiosis, for which beta-lactam antimicrobial drug or external application of
      GM ointment would be effective, and abscess-type cutaneous nocardiosis, which
      recovered with medical treatment for a general bacterial infection was suggested.

PMID- 24682101
TI  - [Handling and culture collection of clinical isolate: focus on preservation and
      distribution of microbial strains for industrial use].

PMID- 24682102
TI  - Tetrathiafulvalene mono- and bis-1,2,3-triazole precursors by click chemistry:
      structural diversity and reactivity.
AB  - The donor ortho-dimethyl-TTF-(N-n-Bu-1,2,3-triazole) 1,5-isomer has been
      synthesized by click chemistry following a ruthenium-catalyzed azide-alkyne
      cycloaddition procedure. The single crystal X-ray analysis showed a planar
      conformation between the TTF and triazole units and a set of intermolecular
      interactions at the supramolecular level in the solid state. The same procedure
      allowed the preparation of the corresponding ortho-dimethyl-TTF-bis(triazole)
      which was also structurally characterized. Because of the steric hindrance, the
      triazole units are no longer planar with the TTF backbone. The reactivity of the
      triazole ring has been investigated in protonation and alkylation reactions,
      monitored by UV-visible spectroscopy, which clearly showed the red shift of the
      intramolecular charge transfer band. A TTF-methyl-triazolium salt has been
      isolated and analyzed by single crystal X-ray analysis. All of the TTF-triazoles
      and triazolium salts are valuable precursors for radical cation salts due to
      their oxidation potentials and variety of possible intermolecular interactions. 

PMID- 24682103
TI  - Unravelling the prostate-specific antigen controversy: a West of Scotland
      perspective.
AB  - BACKGROUND: The use of serum prostate-specific antigen (PSA) as a screening tool
      for prostate cancer in asymptomatic men is hugely controversial in the light of
      randomised controlled trials failing to demonstrate a benefit without risk of
      significant overtreatment. However, PSA can be used as a tool to risk assess
      disease progression in men with lower urinary tract symptoms suggestive of benign
      prostatic enlargement (LUTS/BPE). The aim of this study was to canvas the
      opinions of West of Scotland Urologists regarding the use of PSA in both
      symptomatic and asymptomatic patients. METHODS: A questionnaire-based survey was
      sent to all the Consultants and Trainees in the West of Scotland. RESULTS: Survey
      response rate was 45% (47/105). In patients <70 years, 93% would perform a PSA
      testing in patients symptomatic of LUTS/BPE, but only 17% would offer PSA
      screening to asymptomatic patients. In patients >70 years, only 48% of urologists
      would perform a PSA if patients were symptomatic and none would offer PSA
      screening. In terms of self-testing, 59% of urologists would have a PSA test if
      symptomatic and 31% of urologists would have PSA screening. CONCLUSIONS: This
      study highlights significant variability in the use of PSA for both asymptomatic
      and symptomatic men. Despite a lack of evidence, PSA screening is still offered
      to asymptomatic men. Further randomised studies are required to determine the
      utility of PSA-based screening algorithms for prostate cancer detection.

PMID- 24682104
TI  - Pseudoaneurysm of the sural artery: a rare complication of lower limb
      angioplasty.
AB  - INTRODUCTION: Percutaneous transluminal angioplasty (PTA) is a common therapeutic
      option for the treatment of peripheral vascular disease. Pseudoaneurysm at the
      puncture site is a well-documented complication in patients. CASE PRESENTATION:
      This case report describes a patient who presented to hospital several days
      following a left superficial femoral and popliteal artery PTA with lower limb
      pain and swelling. The working diagnosis included a deep vein thrombosis based on
      the Wells criteria. However, a combination of a duplex scan and computed
      tomography angiography confirmed a clinically rare occurrence of pseudoaneurysm
      of the sural artery, a branch of the popliteal artery. This was managed
      successfully with a thrombin injection, leading to complete resolution of the
      patient's symptoms. CONCLUSION: This case highlights the importance of the
      technical aspects of performing a PTA. We believe that the guide-wire position
      was not confirmed to be completely in the popliteal artery upon inflation of the
      balloon.

PMID- 24682106
TI  - Real-time breath analysis with active capillary plasma ionization-ambient mass
      spectrometry.
AB  - On-line analysis of exhaled human breath is a growing area in analytical science,
      for applications such as fast and non-invasive medical diagnosis and monitoring.
      In this work, we present a novel approach based on ambient ionization of
      compounds in breath and subsequent real-time mass spectrometric analysis. We
      introduce a plasma ionization source for this purpose, which has no need for
      additional gases, is very small, and is easily interfaced with virtually any
      commercial atmospheric pressure ionization mass spectrometer (API-MS) without
      major modifications. If an API-MS instrument exists in a laboratory, the cost to
      implement this technology is only around [Formula: see text]500, far less than
      the investment for a specialized mass spectrometric system designed for volatile
      organic compounds (VOCs) analysis. In this proof-of-principle study we were able
      to measure mass spectra of exhaled human breath and found these to be comparable
      to spectra obtained with other electrospray-based methods. We detected over 100
      VOCs, including relevant metabolites like fatty acids, with molecular weights
      extending up to 340 Da. In addition, we were able to monitor the time-dependent
      evolution of the peaks and show the enhancement of the metabolism after a meal.
      We conclude that this approach may complement current methods to analyze breath
      or other types of vapors, offering an affordable option to upgrade any pre
      existing API-MS to a real-time breath analyzer. 

PMID- 24682105
TI  - A key role for neuropeptide Y in lifespan extension and cancer suppression via
      dietary restriction.
AB  - Knowledge of genes essential for the life-extending effect of dietary restriction
      (DR) in mammals is incomplete. In this study, we found that neuropeptide Y (Npy),
      which mediates physiological adaptations to energy deficits, is an essential link
      between DR and longevity in mice. The lifespan-prolonging effect of lifelong 30%
      DR was attenuated in Npy-null mice, as was the effect on the occurrence of
      spontaneous tumors and oxidative stress responses in comparison to wild-type
      mice. In contrast, the physiological processes activated during adaptation to DR,
      including inhibition of anabolic signaling molecules (insulin and insulin-like
      growth factor-1), modulation of adipokine and corticosterone levels, and
      preferential fatty acid oxidation, were unaffected by the absence of Npy. These
      results suggest a key role for Npy in mediating the effects of DR. We also
      provide evidence that most of the physiological adaptations to DR could be
      achieved in mice without Npy. 

PMID- 24682107
TI  - Evaluation of the effect of static magnetic fields combined with human hepatocyte
      growth factor on human satellite cell cultures.
AB  - Tissue engineering is a promising research field, which aims to create new
      functional muscle tissue in vitro, by utilizing the myogenic differentiation
      potential of human stem cells. The objective of the present study was to
      determine the effect of static magnetic fields (SMF), combined with the use of
      the myogenic differentiation enhancing hepatocyte growth factor (HGF), on human
      satellite cell cultures, which are one of the preferred stem cell sources in
      skeletal muscle tissue engineering. We performed almarBlue(r) proliferation
      assays and semi-quantitative reverse transcription polymerase chain reaction (RT
      PCR) for the following myogenic markers: desmin (DES), myogenic factor 5 (MYF5),
      myogenic differentiation antigen 1 (MYOD1), myogenin (MYOG), myosin heavy chain
      (MYH) and alpha1 actin (ACTA1) to detect the effects on myogenic maturation.
      Additionally, immunohistochemical staining (ICC) and fusion index (FI)
      determination as independent markers of differentiation were performed on
      satellite cell cultures stimulated with HGF and HGF + SMF with an intensity of 80
      mT. ICC verified the muscle phenotype at all time points. SMF enhanced the
      proliferation of satellite cell cultures treated with HGF. RT-PCR analysis, ICC
      and FI calculation revealed the effects of HGF/SMF on the investigated
      differentiation markers and stimulation with HGF and SMF verified the continuing
      maturation, however no significant increase in analysed markers could be detected
      when compared with control cultures treated with serum cessation. In conclusion,
      HGF or HGF + SMF stimulation of human satellite cell cultures did not lead to the
      desired enhancement of myogenic maturation of human satellite cell cultures
      compared with cell cultures stimulated with growth factor reduction.

PMID- 24682108
TI  - Prevalence of obesity by occupation among US workers: the National Health
      Interview Survey 2004-2011.
AB  - OBJECTIVE: To estimate the prevalence of obesity and the change of prevalence of
      obesity between 2004-2007 and 2008-20011 by occupation among US workers in the
      National Health Interview Survey. METHODS: Self-reported weight and height were
      collected and used to assess obesity (body mass index >= 30 kg/m). Gender-,
      race/ethnicity-, and occupation-specific prevalence of obesity were calculated.
      RESULTS: Prevalence of obesity steadily increased from 2004 through 2008 across
      gender and race/ethnicity but leveled off from 2008 through 2011. Non-Hispanic
      black female workers in health care support (49.2%) and transportation/material
      moving (46.6%) had the highest prevalence of obesity. Prevalence of obesity in
      relatively low-obesity (white-collar) occupations significantly increased between
      2004-2007 and 2008-2011, whereas it did not change significantly in high-obesity
      (blue-collar) occupations. CONCLUSIONS: Workers in all occupational categories
      are appropriate targets for health promotion and intervention programs to reduce
      obesity.

PMID- 24682109
TI  - Emotion and internal experience in Obsessive Compulsive Disorder: reviewing the
      role of alexithymia, anxiety sensitivity and distress tolerance.
AB  - Increasing attention has focused on the role of emotion and internal experience
      in Obsessive Compulsive Disorder (OCD). This review examines three key constructs
      that capture different aspects of understanding, appraisal and tolerance of
      internal states in OCD - alexithymia, anxiety sensitivity (AS) and distress
      tolerance (DT). The review examines the evidence for the role each of these
      constructs plays in OCD and considers whether conclusions can be drawn about the
      implications for our understanding and treatment of OCD. There is evidence that
      all three are elevated in clinical cases compared to controls, but there is no
      evidence that any of the three shows specificity for OCD over other anxiety
      disorders. However, the review has highlighted significant methodological
      heterogeneity and consequent variation in findings that currently limits broader
      conclusions from being drawn. There is an indication that this is a valuable area
      to explore and future studies should focus on deriving greater conceptual clarity
      around these constructs, independently replicating findings, and establishing a
      common methodology to enhance the comparability of studies. Studies exploring the
      ways in which internal experience, cognitions and symptoms may relate to one
      another would be of significant value in developing models that then lead to
      improved treatment approaches. 

PMID- 24682110
TI  - Applying quantitative structure-activity relationship (QSAR) methodology for
      modeling postmortem redistribution of benzodiazepines and tricyclic
      antidepressants.
AB  - Postmortem redistribution (PMR) constitutes a multifaceted process, which
      complicates the interpretation of drug concentrations by forensic toxicologists.
      The present study aimed to apply quantitative structure-activity relationship
      (QSAR) analysis for modeling PMR data of structurally related drugs, 10
      benzodiazepines and 10 tricyclic antidepressants. For benzodiazepines, an
      adequate QSAR model was obtained (R(2) = 0.98, Q(2) = 0.88, RMSEE = 0.12), in
      which energy, ionization and molecular size exerted significant impact. For
      tricyclic antidepressants, an adequate QSAR model with slightly inferior
      statistics (R(2) = 0.95, Q(2) = 0.87, RMSEE = 0.29) was established after
      exclusion of maprotiline, in which energy parameters, basicity character and
      lipophilicity exerted significant contribution. Thus, QSAR analysis could be used
      as a complementary tool to provide an informative illustration of the
      contributing molecular, physicochemical and structural properties in PMR process.
      However, the complexity, non-static and time-dependent nature of PMR endpoints
      raises serious concerns whether QSAR methodology could predict the degree of
      redistribution, highlighting the need for animal-derived PMR data. 

PMID- 24682111
TI  - In vitro metabolism of 3,4-methylenedioxymethamphetamine in human hepatocytes.
AB  - Users of the illicit drug, 3,4-methylenedioxymethamphetamine (MDMA), show signs
      of neurotoxicity. However, the precise mechanism of neurotoxicity caused by use
      of MDMA has not yet been elucidated. Synthetic glutathione (GSH) conjugates of
      MDMA are transported into the brain by the GSH transporter and subsequently
      produce neurotoxicity. The objective of this research is to show direct evidence
      of the formation of GSH adducts of MDMA in human hepatocytes. High-performance
      liquid chromatography coupled with tandem mass spectrometry was utilized to
      examine in vitro incubations of MDMA with cryopreserved human hepatocytes. The
      use of hydrophilic liquid chromatography in combination with linear ion trap mass
      spectrometry permitted the identification of two possible GSH metabolites.
      Enhanced product ion scans of m/z = 499 and 487 amu of extracts from hepatocytes
      treated with 1.0 mM MDMA show a distinct fragmentation pattern (m/z 194.2, 163,
      135, 105), suggesting the formation of MDMA-GSH conjugate, MDMA-SG and 3,4
      dihydroxymethamphetamine-SG. The formation of an MDMA-GSH conjugate was further
      supported by the apparent lack of the same fragmentation pattern from hepatocyte
      samples without MDMA treatment. The results generated from this study yield
      valuable qualitative and quantitative information about the neurotoxic thioether
      metabolites formed from MDMA in humans. 

PMID- 24682112
TI  - Exserohilum infections: review of 48 cases before the 2012 United States
      outbreak.
AB  - Exserohilum species are soilborne fungi that have been uncommon causes of human
      disease. The ongoing outbreak in the United States warrants improved
      understanding of this pathogen. We systematically reviewed all cases of
      Exserohilum spp. infections published before the outbreak in 2012 in order to
      provide a better understanding of the organism and its wider spectrum of human
      disease. Cases of Exserohilum infections were retrieved by searching PubMed.
      Demographic data, underlying conditions, microbiology, clinical manifestations,
      therapy, and outcome were recorded and analyzed. Forty-eight evaluable cases were
      identified from 1975 to 2012. The number of reported cases increased more than
      twofold during the study period (P < 0.01). Most cases occurred in the southern
      United States, India, and Israel. Median age of patients was 25 years, with a
      male predominance. Most infections were due to E. rostratum (60.4%), followed by
      E. longirostratum (6.3%) and E. mcginnisii (2%), while 31.3% were unidentified
      species. The most frequent underlying conditions were immunosuppression (27.2%),
      trauma (16.6%), and atopy (12.5%). Exserohilum disease manifested as systemic
      (73%), cutaneous (25%), corneal (16.7%), and subcutaneous (10.4%) infection.
      Antifungal therapy consisted mainly of amphotericin B (44%) alone or combined
      with a triazole. Surgery was used in 48% of cases and was combined with
      antifungal therapy in 31%. The all-cause mortality was 23%, which was higher in
      patients with preexisting immunosuppression (56.2%; odds ratio 15.4; 95%
      confidence interval, 2.7-88.6). This review of the pre-outbreak reported cases
      highlights several aspects of epidemiology, clinical presentation, risk factors,
      and management of this unusual pathogen.

PMID- 24682113
TI  - Molecular identification, genotyping, and antifungal susceptibility testing of
      clinically relevant Trichosporon species from Argentina.
AB  - Trichosporon species are emerging causative agents of mycoses; most are
      documented in immunocompromised patients. Species identification is important for
      epidemiological purposes in order to better define species clinical associations
      and to improve antifungal treatment. Here, we studied a collection of 41
      Trichosporon strains recovered from hospitalized patients in Argentina. All
      strains were identified by sequencing the D1/D2 domain of 26S, internal
      transcribed spacer (ITS) regions, and intergenic spacer 1 (IGS1) region. In
      addition, we determined the IGS1 region genotypes of the suspected T. asahii
      strains. Antifungal susceptibility of all strains was investigated. Thirty-eight
      of the 41 strains in this study were identified as follows: 29 T. asahii, 3 T.
      inkin, 3 T. montevideense, 2 T. faecale, and 1 T. dermatis. The identity of the
      three remaining strains could not be confirmed. Strain DMic 114126 (Culture
      collection of the Mycology Department (DMic), National Institute of Infectious
      Diseases "Dr. Carlos G. Malbran".) may represent a T. asahii subspecies or a new
      Trichosporon species, strain DMic 94750 was identified as T. cf. guehoae and
      strain DMic 114132 as T. cf. akiyoshidainum. The distribution of T. asahii
      genotypes was as follows: 12 genotype 3, 9 genotype 1, 4 genotype 4, 2 genotype
      5, and 2 genotype 7. Amphotericin B minimal inhibitory concentrations (MICs) were
      <=1 mg/l for 78% (32/41) of the strains. Fluconazole MICs were >=2 mg/l for 90%
      of the strains. However, itraconazole, voriconazole, ketoconazole, and
      posaconazole MICs were <=1 mg/l for 100% of the strains. Terbinafine MICs were
      <=1 mg/l for 98% 40/41 of the strains.

PMID- 24682115
TI  - Is a decline in estimated GFR an appropriate surrogate end point for
      renoprotection drug trials?

PMID- 24682117
TI  - Alternatively activated macrophages as therapeutic agents for kidney disease: in
      vivo stability is a key factor.
AB  - Infusing ex vivo-generated alternatively activated macrophages (AAM) has shown
      promise in experimental systems as a therapeutic strategy for inflammatory kidney
      disease. In the mouse Adriamycin nephropathy model, however, Cao et al. report
      that AAM derived from bone marrow precursors fail to ameliorate disease severity.
      Absence of the anticipated protective effect resulted from a loss of macrophage
      anti-inflammatory (M2) phenotype following trafficking to injured kidney-an
      effect that was mediated by localized colony-stimulating factor-1-dependent
      macrophage proliferation. 

PMID- 24682118
TI  - Sphingosine-1-phosphate receptor signaling during acute kidney injury: the tissue
      is the issue.
AB  - Sphingosine-1-phosphate is a lipid mediator that has been implicated in
      protection from acute kidney injury (AKI) by activation of the sphingosine-1
      phosphate 1 receptor (S1P1R). The research team of H. Thomas Lee demonstrates
      that mice with induced deletion of S1P1R on endothelial cells experience
      increased ischemia-induced AKI. These findings have important translational
      implications. Indeed, S1P1R agonists have been used for the treatment of patients
      suffering from autoimmune encephalitis. Endothelial S1P1R signaling could be
      targeted for AKI prevention in surgical patients. 

PMID- 24682119
TI  - Urine proteomics for acute kidney injury prognosis: another player and the long
      road ahead.
AB  - Urine represents a mine for proteomic markers of renal diseases, but its analysis
      is hindered by unresolved technical issues. Aregger et al. used an unbiased
      proteomics approach to analyze urine of critically ill patients. They discovered
      insulin-like growth factor-binding protein 7 (IGFBP-7) and linked it to acute
      kidney injury (AKI) outcome. Future efforts should address the biology of IGFBP-7
      and related proteins to determine their role in AKI. 

PMID- 24682120
TI  - Estimation of fluid volumes in hemodialysis patients: comparing bioimpedance with
      isotopic and dilution methods.
AB  - Both single-frequency bioimpedance and multiple-frequency spectroscopy are
      equally accurate in measuring total-body water and intracellular fluid. Estimates
      are consistent at a population level but not at the individual level, because of
      wide limits of agreement. There is no real 'gold standard' method providing
      estimates with absolute accuracy (in liters). Bioelectrical impedance vector
      analysis allows comparison of the actual body impedance with that of the
      reference population (in Omega/m). Hemodialysis prescription can be optimized
      with the use of this feedback. 

PMID- 24682121
TI  - Selecting the optimal peritoneal dialysis catheter.
AB  - As the incidence of end stage renal disease increases across the globe, so too do
      the survival rates of peritoneal dialysis patients. It is notable though, that
      peritoneal dialysis utilization does not follow at the same pace, attributable
      into the high technique failure rates, mainly due to peritoneal catheter
      dysfunction. A new systematic review and meta-analysis by Hagen et al. reveals
      that the use of straight catheters may improve outcomes and technique survival. 

PMID- 24682122
TI  - A window into immunosuppressant immunoregulation: recipient conversion to
      rapamycin increases potentially tolerogenic immune cells.
AB  - Mechanistic target of rapamycin inhibitors (mTORi) have a complex
      immunoregulatory profile in both animal models and transplant patients. Studies
      suggest that mTORi act as tolerance-supporting and regulatory T cell (Treg)
      promoting immunosuppressants. Yet proinflammatory influences on myeloid dendritic
      cells have been established. Insight is needed into the impact of mTORi on immune
      cells. Stallone et al. describe a clinical study identifying a potential
      immunoregulatory pathway involving plasmacytoid dendritic cells and Tregs in
      renal transplant patients on mTORi. 

PMID- 24682123
TI  - The perils of clinical trials.
AB  - When the maximal reabsorptive capacity for glucose is lowered by blockade of the
      activity of sodium-glucose cotransporter-2 (SGLT2), glucosuria occurs in
      proportion to the plasma glucose and glomerular filtration rate. Accordingly, the
      modest, 0.44%, hemoglobin A1c reduction found by Kohan et al. in diabetic
      patients with relatively good glycemic control and chronic kidney disease stage 3
      treated with an SGLT2 inhibitor might have been anticipated. The 0.32% fall in
      hemoglobin A1c in the placebo group, however, seems less expected. 

PMID- 24682124
TI  - The challenges and surprises of a definitive molecular genetic diagnosis.
AB  - Making precise molecular genetic diagnoses in inherited kidney diseases is
      important. Gee et al. describe families with end-stage renal disease secondary to
      a presumed diagnosis of a nephronophthisis-related ciliopathy (NPHP-RC), in whom
      a combination of approaches allowed genetic diagnoses to be made. New genetic
      approaches to the diagnosis of childhood renal failure are becoming mainstream
      and will hopefully improve patient management, avoid clinical misdiagnoses,
      reduce the need for invasive investigations, and allow screening of at-risk
      relatives. 

PMID- 24682125
TI  - Diffusion-weighted magnetic resonance imaging: a non-nephrotoxic prompt
      assessment of kidney involvement in IgG4-related disease.

PMID- 24682126
TI  - Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing
      regulatory T cells through splenocyte interactions.

PMID- 24682127
TI  - Serum beta2-microglobulin predicts mortality and transplant outcomes.

PMID- 24682128
TI  - Pyeloureteritis cystica.

PMID- 24682129
TI  - Posterior nutcracker syndrome: an infrequent cause of hematuria.

PMID- 24682130
TI  - The case | A hemodialysis patient with bullous skin lesions.

PMID- 24682133
TI  - Elephantiasis nostras verrucosa.

PMID- 24682131
TI  - Developmental trajectories of cortical-subcortical interactions underlying the
      evaluation of trust in adolescence.
AB  - Social decision making is guided by the ability to intuitively judge personal
      attributes, including analysis of facial features to infer the trustworthiness of
      others. Although the neural basis for trustworthiness evaluation is well
      characterized in adults, less is known about its development during adolescence.
      We used event-related functional magnetic resonance imaging to examine age
      related changes in neural activation and functional connectivity during the
      evaluation of trust in faces in a sample of adolescent females. During scanning,
      participants viewed masked presentations of faces and rated their
      trustworthiness. Parametric modeling of trust ratings revealed enhanced
      activation in amygdala and insula to untrustworthy faces, effects which peaked
      during mid-adolescence. Analysis of amygdala functional connectivity demonstrated
      enhanced amygdala-insula coupling during the evaluation of untrustworthy faces.
      This boost in connectivity was attenuated during mid-adolescence, suggesting a
      functional transition within face-processing circuits. Together, these findings
      underscore adolescence as a period of reorganization in neural circuits
      underlying socioemotional behavior. 

PMID- 24682134
TI  - Pitfall in lung ultrasound: 'pseudo B-line' seen in both hydropneumothorax and in
      a cup of coffee.
AB  - One of the lung ultrasound (LUS) signs which can be used to exclude the presence
      of pneumothorax is the B-line artefact. The presence of a B-line artefact
      indicates that the two pleural blades are in contact. Most of the research
      describing LUS for the diagnosis of pneumothorax is limited to pneumothorax
      without concomitant pleural effusion. This case report presents how a B-line was
      visualised using LUS in a patient with hydropneumothorax and, in addition, a
      simple model is used to provide a possible explanation on this phenomenon. 

PMID- 24682132
TI  - 'Ecstasy' as a social drug: MDMA preferentially affects responses to emotional
      stimuli with social content.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is used recreationally to
      improve mood and sociability, and has generated clinical interest as a possible
      adjunct to psychotherapy. One way that MDMA may produce positive 'prosocial'
      effects is by changing responses to emotional stimuli, especially stimuli with
      social content. Here, we examined for the first time how MDMA affects subjective
      responses to positive, negative and neutral emotional pictures with and without
      social content. We hypothesized that MDMA would dose-dependently increase
      reactivity to positive emotional stimuli and dampen reactivity to negative
      stimuli, and that these effects would be most pronounced for pictures with people
      in them. The data were obtained from two studies using similar designs with
      healthy occasional MDMA users (total N = 101). During each session, participants
      received MDMA (0, 0.75 and 1.5 mg/kg oral), and then rated their positive and
      negative responses to standardized positive, negative and neutral pictures with
      and without social content. MDMA increased positive ratings of positive social
      pictures, but reduced positive ratings of non-social positive pictures. We
      speculate this 'socially selective' effect contributes to the prosocial effects
      of MDMA by increasing the comparative value of social contact and closeness with
      others. This effect may also contribute to its attractiveness to recreational
      users. 

PMID- 24682135
TI  - Midgut malrotation presenting with left-sided acute appendicitis and CT inversion
      sign.
AB  - In patients presenting with abdominal pain, appendicitis is the most common
      surgical disorder. Appendicitis causing pain in the left lower quadrant is
      extremely rare and can occur with congenital abnormalities that include true left
      sided appendix or as an atypical presentation of right-sided long appendix, which
      projects into the left lower quadrant. We report a case of a 69-year-old man
      showing midgut malrotation with acute appendicitis presenting as left lower
      quadrant abdominal pain. 

PMID- 24682136
TI  - Abdominal cocoon.
AB  - Intestinal obstruction secondary to cocoon formation is not common. We report a
      case of a patient who had presented with abdominal pain and distension
      accompanied by vomiting. Investigations, laparotomy and histology together
      revealed primary peritoneal carcinoma as the cause of the patient's symptoms. 

PMID- 24682137
TI  - Management of digital vasculopathy in systemic sclerosis: benefits of multiple
      courses of endothelin-1 receptor antagonists.
AB  - Two patients with scleroderma and recurrent digital ulcers (DUs) were treated
      with bosentan for 6 months. Treatment was associated with a reduction in the
      number of new DUs; however, DUs recurred on treatment discontinuation. This case
      report illustrates the positive response of digital vasculopathy to bosentan and
      describes the benefits of multiple bosentan treatment courses in these patients. 

PMID- 24682138
TI  - Double trouble: hypertrophic cardiomyopathy coexistent with malignant anomalous
      right coronary artery.
AB  - A 40-year-old man with no cardiac history was admitted for evaluation of atypical
      chest pain of 1-month duration. On investigation he was found to have
      hypertrophic cardiomyopathy and an anomalous right coronary artery arising from
      the left sinus of Valsalva. This is of great clinical significance as both these
      conditions are independently associated with sudden cardiac death. Following
      extensive risk assessment and detailed discussion with the patient, he was
      discharged on medical therapy, comprising bisoprolol, aspirin and rosuvastatin.
      He has remained free of symptoms for 1 year. This report describes the rare
      coexistence of these two distinct clinical entities, examines the various
      treatment options and provides support for medical management as an acceptable
      treatment strategy in appropriately selected cases. 

PMID- 24682139
TI  - Arthroprosthetic cobaltism and pseudotumour also occur in patients with small
      diameter femoral ball head metal-on-metal total hip arthroplasties.
AB  - Metal-on-metal implants have been widely discredited in public during the past
      few months. At the same time patients' awareness has risen leading to an
      increased number of consultations regarding the topic. As hip resurfacings and
      total hip arthroplasties with large diameter femoral ball heads are already known
      for excessive metal wear, even small diameter ball heads with low friction get
      into focus now. We report a case of a 75-year-old man with recurrent hip pain
      almost 14 years after low friction metal-on-metal total hip arthroplasty. In
      addition to elevated serum cobalt levels, a type IV sensitivity reaction to
      cobalt could be noted. Explantation of a highly worn small diameter femoral ball
      head as well as development of the so-called pseudotumour indicate that all
      patients should be screened for signs of metal wear regardless of their specific
      risk factors or the type of metal-on-metal implant. 

PMID- 24682140
TI  - Central pontine myelinolysis: electrolytes and beyond.
AB  - Central pontine myelinolysis (CPM), which is a component of the osmotic
      demyelination syndrome (ODS), is a frequent neurological complication that
      follows rapid correction of hyponatraemia. However, there are other predisposing
      risk factors (chronic alcoholism, hypokalaemia) that perpetuate the development
      of ODS. We report a case of a 39-year-old woman with a history of chronic
      alcoholism who presented to us with progressive neurological deficits
      (paraparesis, paresthesias). She was initially detected to have coexisting
      hypokalaemia which was eventually rectified with potassium supplementation.
      However, she continued to experience progressive worsening of her neurological
      symptoms despite adequate potassium supplementation. Therefore, a neurological
      opinion was sought for and she was diagnosed with CPM based on a background of
      chronic alcoholism and malnutrition; an MRI of the brain showed a hyperintense
      signal in the central pontine region. Following the diagnosis of CPM, she was
      rehabilitated with occupational and physiotherapy. 

PMID- 24682141
TI  - Collagenous sprue: a coeliac disease look-alike with different treatment
      strategy.
AB  - Collagenous sprue is a rare clinicopathological condition of the small bowel. It
      is characterised by abnormal subepithelial collagen deposition and is typically
      associated with malabsorption, diarrhoea and weight loss. The clinical features
      of collagenous sprue often resemble those of coeliac disease and together with
      frequent histological findings like mucosal thinning and intraepithelial
      lymphocytosis the diagnosis may be hard to reach without awareness of this
      condition. While coeliac disease is treated using gluten restriction, collagenous
      sprue is, however, not improved by this intervention. In cases of diet-refractory
      'coeliac disease' it is therefore essential to consider collagenous sprue to
      initiate treatment at an early stage to prevent the fibrotic progression. Here,
      we report a case of a 78-year-old man with collagenous sprue and present the
      clinical and histological manifestations as well as the successful treatment
      course that he underwent. 

PMID- 24682142
TI  - Creutzfeldt-Jakob disease: typical imaging findings.

PMID- 24682143
TI  - Twin ostial openings in the left posterior aortic sinus: a pictorial overview of
      coronary revascularisation and aortic valve replacement in a patient with absent
      left main artery.

PMID- 24682144
TI  - 'Monolateral' superior vena cava syndrome: right internal jugular vein occlusion.

PMID- 24682145
TI  - A statistical method to base nutrient recommendations on meta-analysis of intake
      and health-related status biomarkers.
AB  - Nutrient recommendations in use today are often derived from relatively old data
      of few studies with few individuals. However, for many nutrients, including
      vitamin B-12, extensive data have now become available from both observational
      studies and randomized controlled trials, addressing the relation between intake
      and health-related status biomarkers. The purpose of this article is to provide
      new methodology for dietary planning based on dose-response data and meta
      analysis. The methodology builds on existing work, and is consistent with current
      methodology and measurement error models for dietary assessment. The detailed
      purposes of this paper are twofold. Firstly, to define a Population Nutrient
      Level (PNL) for dietary planning in groups. Secondly, to show how data from
      different sources can be combined in an extended meta-analysis of intake-status
      datasets for estimating PNL as well as other nutrient intake values, such as the
      Average Nutrient Requirement (ANR) and the Individual Nutrient Level (INL). For
      this, a computational method is presented for comparing a bivariate lognormal
      distribution to a health criterion value. Procedures to meta-analyse available
      data in different ways are described. Example calculations on vitamin B-12
      requirements were made for four models, assuming different ways of estimating the
      dose-response relation, and different values of the health criterion. Resulting
      estimates of ANRs and less so for INLs were found to be sensitive to model
      assumptions, whereas estimates of PNLs were much less sensitive to these
      assumptions as they were closer to the average nutrient intake in the available
      data. 

PMID- 24682146
TI  - An off-the-shelf sensing system for physiological phosphates.
AB  - An off-the-shelf supramolecular sensing system was designed to discriminate
      biologically relevant phosphates in neutral water using multivariate data
      analysis. The system is based on an indicator displacement assay comprising only
      two unmodified commercially available components: a dendritic poly-electrolyte
      and a common fluorescent dye. Effective discrimination of nucleotide diphosphates
      and inorganic diphosphate was achieved through principal component analysis
      (PCA). 

PMID- 24682147
TI  - Quantitative determination of major platelet activating factors from human
      plasma.
AB  - Platelet activating factor (PAF) is a potent lipid mediator that is involved in
      many important biological functions, including platelet aggregation and neuronal
      differentiation. Although an ELISA assay has been used to measure PAF levels, it
      cannot distinguish between its isoforms. To achieve this, liquid chromatography
      tandem mass spectrometry (LC-MS/MS) has been used instead. However, isobaric
      lysophosphatidylcholine (lyso PC), which is often present in large amounts in
      complex biological samples and has similar retention times in many LC conditions,
      can affect the accurate measurement of PAF. The present study examined the
      fragmentation behavior of major PAF and lyso PC during various MS/MS conditions.
      Fragment ions at m/z 184 and at m/z 104 were abundantly observed from MS/MS of
      lyso PCs. PAF provided a dominant fragment ion at m/z 184, but a fragment ion at
      m/z 104 was almost never produced, regardless of the collision energy. Thus, the
      two fragment ions at m/z 184 and m/z 104 were used to accurately measure PAF
      levels. First, the fragment ion at m/z 184 and the retention time of PAF in LC
      MS/MS were used to identify and quantitate PAF. However, if there were small
      retention time shifts, which are common in multiple sample runs, and lipid
      composition in a sample is very complicated, the fragment ion at m/z 104 was used
      to confirm whether the fragment ion at m/z 184 belonged to PAF. This novel method
      accurately determined the major PAF (C16:0 PAF, C18:0 PAF, and C18:1 PAF) levels
      in human plasma. 

PMID- 24682148
TI  - Highly enantioselective Michael addition of diethyl malonate to chalcones
      catalyzed by cinchona alkaloids-derivatived bifunctional tertiary amine-thioureas
      bearing multiple hydrogen-bonding donors.
AB  - Chalcones are still challenge substrates in Michael reactions, and only limited
      success has been achieved. This work describes a highly enantioselective Michael
      addition of diethyl malonate with chalcones catalyzed by cinchona alkaloids
      derivatived bifunctional tertiary amine-thioureas bearing multiple hydrogen
      bonding donors. 

PMID- 24682149
TI  - Merging of Kirkendall growth and Ostwald ripening: CuO@MnO2 core-shell
      architectures for asymmetric supercapacitors.
AB  - Fabricating hierarchical core-shell nanostructures is currently the subject of
      intensive research in the electrochemical field owing to the hopes it raises for
      making efficient electrodes for high-performance supercapacitors. Here, we
      develop a simple and cost-effective approach to prepare CuO@MnO2 core-shell
      nanostructures without any surfactants and report their applications as
      electrodes for supercapacitors. An asymmetric supercapacitor with CuO@MnO2 core
      shell nanostructure as the positive electrode and activated microwave exfoliated
      graphite oxide (MEGO) as the negative electrode yields an energy density of 22.1
      Wh kg(-1) and a maximum power density of 85.6 kW kg(-1); the device shows a long
      term cycling stability which retains 101.5% of its initial capacitance even after
      10000 cycles. Such a facile strategy to fabricate the hierarchical CuO@MnO2 core
      shell nanostructure with significantly improved functionalities opens up a novel
      avenue to design electrode materials on demand for high-performance
      supercapacitor applications.

PMID- 24682150
TI  - The potential role of sexual conflict and sexual selection in shaping the genomic
      distribution of Mito-nuclear genes.
AB  - Mitochondrial interactions with the nuclear genome represent one of life's most
      important co-evolved mutualisms. In many organisms, mitochondria are maternally
      inherited, and in these cases, co-transmission between the mitochondrial and
      nuclear genes differs across different parts of the nuclear genome, with genes on
      the X chromosome having two-third probability of co-transmission, compared with
      one-half for genes on autosomes. These asymmetrical inheritance patterns of
      mitochondria and different parts of the nuclear genome have the potential to put
      certain gene combinations in inter-genomic co-adaptation or conflict. Previous
      work in mammals found strong evidence that the X chromosome has a dearth of genes
      that interact with the mitochondria (mito-nuclear genes), suggesting that inter
      genomic conflict might drive genes off the X onto the autosomes for their male
      beneficial effects. Here, we developed this idea to test coadaptation and
      conflict between mito-nuclear gene combinations across phylogenetically
      independent sex chromosomes on a far broader scale. We found that, in addition to
      therian mammals, only Caenorhabditis elegans showed an under-representation of
      mito-nuclear genes on the sex chromosomes. The remaining species studied showed
      no overall bias in their distribution of mito-nuclear genes. We discuss possible
      factors other than inter-genomic conflict that might drive the genomic
      distribution of mito-nuclear genes. 

PMID- 24682151
TI  - Reduction in fecundity and shifts in cellular processes by a native virus on an
      invasive insect.
AB  - Pathogens and their vectors have coevolutionary histories that are intricately
      intertwined with their ecologies, environments, and genetic interactions. The
      soybean aphid, Aphis glycines, is native to East Asia but has quickly become one
      of the most important aphid pests in soybean-growing regions of North America. In
      this study, we used bioassays to examine the effects of feeding on soybean
      infected with a virus it vectors (Soybean mosaic virus [SMV]) and a virus it does
      not vector (Bean pod mottle virus [BPMV]) have on A. glycines survival and
      fecundity. The genetic underpinnings of the observed changes in fitness phenotype
      were explored using RNA-Seq. Aphids fed on SMV-infected soybean had transcriptome
      and fitness profiles that were similar to that of aphids fed on healthy control
      plants. Strikingly, a significant reduction in fecundity was seen in aphids fed
      on BPMV-infected soybean, concurrent with a large and persistent downregulation
      of A. glycines transcripts involved in regular cellular activities. Although
      molecular signatures suggested a small regulatory RNA pathway defense response
      was repressed in aphids feeding on infected plants, BPMV did not appear to be
      replicating in the vector. These results suggest that incompatibilities with BPMV
      or the effects of BPMV infection on soybean caused A. glycines to allot available
      energy resources to survival rather than reproduction and other core cellular
      processes. Ultimately, the detrimental impacts to A. glycines may reflect the
      short tritrophic evolutionary histories between the insect, plant, and virus.

PMID- 24682152
TI  - A nonmitochondrial hydrogen production in Naegleria gruberi.
AB  - Naegleria gruberi is a free-living heterotrophic aerobic amoeba well known for
      its ability to transform from an amoeba to a flagellate form. The genome of N.
      gruberi has been recently published, and in silico predictions demonstrated that
      Naegleria has the capacity for both aerobic respiration and anaerobic
      biochemistry to produce molecular hydrogen in its mitochondria. This finding was
      considered to have fundamental implications on the evolution of mitochondrial
      metabolism and of the last eukaryotic common ancestor. However, no actual
      experimental data have been shown to support this hypothesis. For this reason, we
      have decided to investigate the anaerobic metabolism of the mitochondrion of N.
      gruberi. Using in vivo biochemical assays, we have demonstrated that N. gruberi
      has indeed a functional [FeFe]-hydrogenase, an enzyme that is attributed to
      anaerobic organisms. Surprisingly, in contrast to the published predictions, we
      have demonstrated that hydrogenase is localized exclusively in the cytosol, while
      no hydrogenase activity was associated with mitochondria of the organism. In
      addition, cytosolic localization displayed for HydE, a marker component of
      hydrogenase maturases. Naegleria gruberi, an obligate aerobic organism and one of
      the earliest eukaryotes, is producing hydrogen, a function that raises questions
      on the purpose of this pathway for the lifestyle of the organism and potentially
      on the evolution of eukaryotes.

PMID- 24682153
TI  - Analyses of charophyte chloroplast genomes help characterize the ancestral
      chloroplast genome of land plants.
AB  - Despite the significance of the relationships between embryophytes and their
      charophyte algal ancestors in deciphering the origin and evolutionary success of
      land plants, few chloroplast genomes of the charophyte algae have been
      reconstructed to date. Here, we present new data for three chloroplast genomes of
      the freshwater charophytes Klebsormidium flaccidum (Klebsormidiophyceae),
      Mesotaenium endlicherianum (Zygnematophyceae), and Roya anglica
      (Zygnematophyceae). The chloroplast genome of Klebsormidium has a quadripartite
      organization with exceptionally large inverted repeat (IR) regions and, uniquely
      among streptophytes, has lost the rrn5 and rrn4.5 genes from the ribosomal RNA
      (rRNA) gene cluster operon. The chloroplast genome of Roya differs from other
      zygnematophycean chloroplasts, including the newly sequenced Mesotaenium, by
      having a quadripartite structure that is typical of other streptophytes. On the
      basis of the improbability of the novel gain of IR regions, we infer that the
      quadripartite structure has likely been lost independently in at least three
      zygnematophycean lineages, although the absence of the usual rRNA operonic
      synteny in the IR regions of Roya may indicate their de novo origin.
      Significantly, all zygnematophycean chloroplast genomes have undergone
      substantial genomic rearrangement, which may be the result of ancient
      retroelement activity evidenced by the presence of integrase-like and reverse
      transcriptase-like elements in the Roya chloroplast genome. Our results
      corroborate the close phylogenetic relationship between Zygnematophyceae and land
      plants and identify 89 protein-coding genes and 22 introns present in the
      chloroplast genome at the time of the evolutionary transition of plants to land,
      all of which can be found in the chloroplast genomes of extant charophytes.

PMID- 24682154
TI  - Genome-wide analysis of wild-type Epstein-Barr virus genomes derived from healthy
      individuals of the 1,000 Genomes Project.
AB  - Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV),
      which establishes itself permanently in B cells. Infection by EBV is related to a
      number of diseases including infectious mononucleosis, multiple sclerosis, and
      different types of cancer. So far, only seven complete EBV strains have been
      described, all of them coming from donors presenting EBV-related diseases. To
      perform a detailed comparative genomic analysis of EBV including, for the first
      time, EBV strains derived from healthy individuals, we reconstructed EBV
      sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes
      Project. As strain B95-8 was used to transform B cells to obtain LCLs, it is
      always present, but a specific deletion in its genome sets it apart from natural
      EBV strains. After studying hundreds of individuals, we determined the presence
      of natural EBV in at least 10 of them and obtained a set of variants specific to
      wild-type EBV. By mapping the natural EBV reads into the EBV reference genome
      (NC007605), we constructed nearly complete wild-type viral genomes from three
      individuals. Adding them to the five disease-derived EBV genomic sequences
      available in the literature, we performed an in-depth comparative genomic
      analysis. We found that latency genes harbor more nucleotide diversity than lytic
      genes and that six out of nine latency-related genes, as well as other genes
      involved in viral attachment and entry into host cells, packaging, and the
      capsid, present the molecular signature of accelerated protein evolution rates,
      suggesting rapid host-parasite coevolution.

PMID- 24682155
TI  - Comparative genomics of Taphrina fungi causing varying degrees of tumorous
      deformity in plants.
AB  - Taphrina fungi are biotrophic plant pathogens that cause plant deformity
      diseases. We sequenced the genomes of four Taphrina species-Taphrina wiesneri, T.
      deformans, T. flavorubra, and T. populina-which parasitize Prunus, Cerasus, and
      Populus hosts with varying severity of disease symptoms. High levels of gene
      synteny within Taphrina species were observed, and our comparative analysis
      further revealed that these fungi may utilize multiple strategies in coping with
      the host environment that are also found in some specialized dimorphic species.
      These include species-specific aneuploidy and clusters of highly diverged
      secreted proteins located at subtelomeres. We also identified species differences
      in plant hormone biosynthesis pathways, which may contribute to varying degree of
      disease symptoms. The genomes provide a rich resource for investigation into
      Taphrina biology and evolutionary studies across the basal ascomycetes clade.

PMID- 24682157
TI  - The 8p23 inversion polymorphism determines local recombination heterogeneity
      across human populations.
AB  - For decades, chromosomal inversions have been regarded as fascinating
      evolutionary elements as they are expected to suppress recombination between
      chromosomes with opposite orientations, leading to the accumulation of genetic
      differences between the two configurations over time. Here, making use of
      publicly available population genotype data for the largest polymorphic inversion
      in the human genome (8p23-inv), we assessed whether this inhibitory effect of
      inversion rearrangements led to significant differences in the recombination
      landscape of two homologous DNA segments, with opposite orientation. Our analysis
      revealed that the accumulation of genetic differentiation is positively
      correlated with the variation in recombination profiles. The observed
      recombination dissimilarity between inversion types is consistent across all
      populations analyzed and surpasses the effects of geographic structure,
      suggesting that both structures (orientations) have been evolving independently
      over an extended period of time, despite being subjected to the very same
      demographic history. Aside this mainly independent evolution, we also identified
      a short segment (350 kb, <10% of the whole inversion) in the central region of
      the inversion where the genetic divergence between the two structural haplotypes
      is diminished. Although it is difficult to demonstrate it, this could be due to
      gene flow (possibly via double-crossing over events), which is consistent with
      the higher recombination rates surrounding this segment. This study demonstrates
      for the first time that chromosomal inversions influence the recombination
      landscape at a fine-scale and highlights the role of these rearrangements as
      drivers of genome evolution. 

PMID- 24682156
TI  - Ancient and recent selective pressures shaped genetic diversity at AIM2-like
      nucleic acid sensors.
AB  - AIM2-like receptors (ALRs) are a family of nucleic acid sensors essential for
      innate immune responses against viruses and bacteria. We performed an
      evolutionary analysis of ALR genes (MNDA, PYHIN1, IFI16, and AIM2) by analyzing
      inter- and intraspecies diversity. Maximum-likelihood analyses indicated that
      IFI16 and AIM2 evolved adaptively in primates, with branch-specific selection at
      the catarrhini lineage for IFI16. Application of a population genetics
      phylogenetics approach also allowed identification of positive selection events
      in the human lineage. Positive selection in primates targeted sites located at
      the DNA-binding interface in both IFI16 and AIM2. In IFI16, several sites
      positively selected in primates and in the human lineage were located in the PYD
      domain, which is involved in protein-protein interaction and is bound by a human
      cytomegalovirus immune evasion protein. Finally, positive selection was found to
      target nuclear localization signals in IFI16 and the spacer region separating the
      two HIN domains. Population genetic analysis in humans revealed that an IFI16
      genic region has been a target of long-standing balancing selection, possibly
      acting on two nonsynonymous polymorphisms located in the spacer region. Data
      herein indicate that ALRs have been repeatedly targeted by natural selection. The
      balancing selection region in IFI16 carries a variant with opposite risk effect
      for distinct autoimmune diseases, suggesting antagonistic pleiotropy. We propose
      that the underlying scenario is the result of an ancestral and still ongoing host
      pathogen arms race and that the maintenance of susceptibility alleles for
      autoimmune diseases at IFI16 represents an evolutionary trade-off.

PMID- 24682158
TI  - Acetic acid bacteria genomes reveal functional traits for adaptation to life in
      insect guts.
AB  - Acetic acid bacteria (AAB) live in sugar rich environments, including food
      matrices, plant tissues, and the gut of sugar-feeding insects. By comparing the
      newly sequenced genomes of Asaia platycodi and Saccharibacter sp., symbionts of
      Anopheles stephensi and Apis mellifera, respectively, with those of 14 other AAB,
      we provide a genomic view of the evolutionary pattern of this bacterial group and
      clues on traits that explain the success of AAB as insect symbionts. A specific
      pre-adaptive trait, cytochrome bo3 ubiquinol oxidase, appears ancestral in AAB
      and shows a phylogeny that is congruent with that of the genomes. The functional
      properties of this terminal oxidase might have allowed AAB to adapt to the
      diverse oxygen levels of arthropod guts.

PMID- 24682160
TI  - Chemical sensors for breath gas analysis: the latest developments at the Breath
      Analysis Summit 2013.
AB  - Profiling the body chemistry by means of volatile organic compounds (VOCs) in the
      breath opens exciting new avenues in medical diagnostics. Gas sensors could
      provide ideal platforms for realizing portable, hand-held breath testing devices
      in the near future. This review summarizes the latest developments and
      applications in the field of chemical sensors for diagnostic breath testing that
      were presented at the Breath Analysis Summit 2013 in Wallerfangen, Germany.
      Considerable progress has been made towards clinically applicable breath testing
      devices, especially by utilizing chemo-sensitive nanomaterials. Examples of
      several specialized breath testing applications are presented that are either
      based on stand-alone nanomaterial-based sensors being highly sensitive and
      specific to individual breath compounds over others, or on combinations of
      several highly specific sensors, or on experimental nanomaterial-based sensors
      arrays. Other interesting approaches include the adaption of a commercially
      available MOx-based sensor array to indirect breath testing applications, using a
      sample pre-concentration method, and the development of compact integrated GC
      sensor systems. The recent trend towards device integration has led to the
      development of fully integrated prototypes of point-of-care devices. We describe
      and compare the performance of several prototypes that are based on different
      sensing technologies and evaluate their potential as low-cost and readily
      available next-generation medical devices. 

PMID- 24682161
TI  - Effects of genetic polymorphisms of CYP2D6, CYP3A5, and ABCB1 on the steady-state
      plasma concentrations of aripiprazole and its active metabolite,
      dehydroaripiprazole, in Japanese patients with schizophrenia.
AB  - BACKGROUND: We studied the effects of various factors, including genetic
      polymorphisms of the cytochrome P450 (CYP) 2D6, CYP3A5, and ABCB1, age, gender,
      and smoking habit on the steady-state plasma concentrations of aripiprazole and
      its active metabolite, dehydroaripiprazole, in 89 patients with schizophrenia (46
      males, 43 females). METHODS: All patients had been receiving fixed doses of
      aripiprazole for at least 2 weeks. The daily doses were 24 mg (n = 56) and 12 mg
      (n = 33). No other drugs except biperiden and flunitrazepam were coadministered.
      Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using
      liquid chromatography with mass-spectrometric detection. The CYP2D6 (CYP2D6*5,
      CYP2D6*10, and CYP2D6*14), CYP3A5 (CYP3A5*3), and ABCB1 (C3435T and G2677T/A)
      genotypes were identified by PCR analyses. RESULTS: The mean concentration/dose
      ratios of aripiprazole and the sum of aripiprazole and dehydroaripiprazole were
      significantly higher in patients with 1 (P < 0.01 and P < 0.01) or 2 (P < 0.001
      and P < 0.05) mutated alleles for CYP2D6 than in those without mutated alleles.
      No differences were found in the values of dehydroaripiprazole among CYP2D6
      genotypes. There were no differences in the values of aripiprazole,
      dehydroaripiprazole, and the sum of the 2 compounds among CYP3A5 or the 2 ABCB1
      variants. Multiple regression analyses including these polymorphisms, age,
      gender, and smoking habit showed that only the number of mutated alleles for
      CYP2D6 was correlated with mean concentration/dose ratios of aripiprazole
      [standardized partial correlation coefficients (beta) = 0.420, P < 0.001] and the
      sum of the 2 compounds (standardized beta = 0.335, P < 0.01). CONCLUSIONS: The
      findings of this study suggest that CYP2D6 genotypes play an important role in
      controlling steady-state plasma concentrations of aripiprazole and the sum of
      aripiprazole and dehydroaripiprazole in Asian subjects, whereas CYP3A5 and ABCB1
      genotypes seemed unlikely to have an impact.

PMID- 24682162
TI  - Effects of [C2mim][OAc] (1-ethyl-3-methyl-imidazolium acetate) on the growth of
      wheat seedlings under Cd2+ stress.
AB  - The joint effect on the growth of wheat seedlings under Cd(2+) stress (0, 0.5
      mmol L(-1)) and [C2mim][OAc] with a series of concentrations (0, 100, 200, 300,
      400, 500 mg L(-1)) was investigated. Physiological characteristics including
      superoxide dismutases, peroxidases, catalase and malondialdehyde were studied in
      hydroponic and soil cultures. Results indicated that, compared to samples treated
      under Cd(2+) stress alone, joint treatment groups showed Cd(2+) stress was
      mitigated by ionic liquid at appropriate concentrations (<= 400 mg L(-1) in
      hydroponic treatments and <= 300 mg L(-1) in soil culture treatments). Use of
      inductively coupled plasma mass spectroscopy showed less Cd(2+) in organelles in
      the joint treatment group. This phenomenon could be due to [C2mim][OAc] forming
      metal complexes with Cd(2+), thus reducing the amount of free Cd(2+) available
      for absorption by the seedlings.

PMID- 24682159
TI  - Association of cadmium, lead and mercury with paraoxonase 1 activity in women.
AB  - BACKGROUND: The activity of paraoxonase 1 (PON1), an antioxidant enzyme whose
      polymorphisms have been associated with cancer risk, may be associated with
      metals exposure. OBJECTIVE: To evaluate PON1 activity in relation to cadmium,
      lead, and mercury levels in healthy, premenopausal women. METHODS: Women from
      upstate New York were followed for >= two menstrual cycles. Repeated measures
      linear mixed models estimated the association between cadmium, lead, and mercury
      levels (by tertile: T1, T2, T3) and PON1 arylesterase (PON1A) and PON1
      paraoxonase (PON1P) activity, separately. Analyses were stratified by PON1 Q192R
      phenotype and un-stratified. RESULTS: Median blood cadmium, lead, and mercury
      concentrations were 0.30 ug/L, 0.87 ug/dL, and 1.15 ug/L. In un-stratified
      analyses cadmium and mercury were associated with decreased PON1A activity (T2
      vs. T1; not T3 vs. T1) but metals were not associated with PON1P. Phenotypes were
      distributed between QQ (n = 99), QR (n = 117), and RR (n = 34). Cadmium was
      associated with decreased PON1A activity for QR and RR phenotypes comparing T2
      vs. T1 (-14.4% 95% confidence interval [CI] [-20.1, -8.4] and -27.9% [-39.5, 
      14.0],). Lead was associated with decreased PON1A (RR phenotype, T3 vs. T1 -18.9%
      [-32.5, -2.5]; T2 vs. T1 -19.6% [-32.4, -4.4]). Cadmium was associated with lower
      PON1P comparing T2 vs. T1 for the RR (-34.9% [-51.5, -12.5]) and QR phenotypes (
      9.5% [-18.1, 0.0]) but not comparing T3 vs. T1. Cadmium was associated with
      increases in PON1P levels (QQ phenotype, T3 vs. T1 24.5% [7.0, 44.9]) and mercury
      was associated with increased PON1A levels (QQ phenotype, T3 vs. T1 6.2% [0.2,
      12.6]). Mercury was associated with decreased PON1P (RR phenotype, T2 vs. T1 
      22.8 [-37.8, -4.1]). CONCLUSION: Blood metals were associated with PON1 activity
      and these effects varied by phenotype. However, there was not a linear dose
      response and these findings await replication.

PMID- 24682163
TI  - Wound complications associated with bone morphogenetic protein-2 in orthopaedic
      trauma surgery.
AB  - OBJECTIVE: To document the incidence of postoperative wound complications
      associated with the use of rhBMP-2 in a large series of patients for both acute
      traumatic and reconstructive extremity cases. DESIGN: Retrospective chart and
      radiographic review. SETTING: Level I trauma center. METHODS: A retrospective
      chart and x-ray review was performed on cases between 2002 and 2009, in which
      rhBMP-2 (Infuse) was used in acute trauma or posttraumatic reconstruction. The
      following data points were collected: age, surgical site, purpose (acute vs.
      reconstructive), associated wound factors (open fractures, soft tissue injury
      requiring coverage, or history of infection), signs of infection (seroma,
      erythema, prolonged drainage, abscess), reoperation rate secondary to wound
      complication, culture results, and union. These cases were then compared with a
      matched cohort without the use of bone morphogenetic protein-2 (matched for age,
      type of case, anatomic site, and open injury) for statistical analysis. RESULTS:
      Group 1 was comprised a total of 193 patients whose treatment included rhBMP-2
      (155 reconstructive and 38 acute open fractures). Group 2 was comprised 181
      patients treated without the use of rhBMP-2 (145 reconstructive and 36 acute open
      fractures). The incidences of documented wound complications were 31% (60/193) in
      group 1 and 18% (33/181) in group 2 (P = 0.004). Reoperation rates for wound
      complications were in 3.1% of group 1 and 8.3% of group 2 (P = 0.04). Age, sex,
      anatomic site, acute trauma, open fracture, and the need for soft tissue
      reconstruction did not correlate with the need to return to the operating room
      for presumed or actual wound infection. The rates of union between rhBMP-2 and
      control groups were 90% versus 74% (P < 0.001); for acute trauma cases, 94%
      versus 79% (P = 0.220); and for reconstructive cases, 89% versus 73% (P = 0.002).
      CONCLUSIONS: The use of rhBMP-2 in both acute traumatic and posttraumatic
      reconstructive extremity surgery may increase the incidence of prolonged
      postoperative serous wound drainage. However, this does not seem to correlate
      with an increased incidence of postoperative wound infection or the need for
      reoperation. The use of rhBMP-2 seems to have a beneficial effect in improving
      union rates for both acute trauma and posttraumatic reconstruction of the
      extremities (P = 0.002); however, this and the mechanism for prolonged serous
      drainage require further study before definitive recommendations can be made.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24682164
TI  - Proximal humerus fractures with associated axillary artery injury.
AB  - Proximal humerus fractures have rarely been associated with injuries to the
      axillary artery. Most of the fractures described have been Neer 2-part surgical
      neck fractures with medialization of the shaft fragment and resultant laceration
      or thrombosis of the axillary artery. No intraoperative deaths have been
      reported. We present a series of 3 proximal humerus fractures, 2 of which are
      Neer 3- to 4-part anterior fracture dislocations, and associated axillary artery
      injury. There were 2 mortalities, 1 intraoperative. After a thorough review of
      the English literature, we identified an additional 11 cases of axillary artery
      injury associated with proximal humerus fracture. The purpose of this study was
      to heighten the clinical suspicion of this vascular injury in patients with
      proximal humerus fracture dislocations and surgical neck fractures with shaft
      medialization, as well as to review pathogenesis and guide management decisions.

PMID- 24682165
TI  - Effect of static electronic advertising signs on road safety: an experimental
      case study.
AB  - As technology continues to advance, the outdoor advertising industry is taking
      advantage of electronic signs, some of which are static electronic signs (SES),
      with the ability to automatically change the message shown on the sign at regular
      intervals. Studies indicate that SES has a negative impact on the drivers' visual
      attention and on vehicle control. However, the actual effects of the SES on the
      number of collisions have been difficult to prove conclusively. The objective of
      this article is to generate a clear understanding of the safety impacts of SES on
      the number collisions by conducting a before-and-after analysis with comparison
      groups. The analysis was based on a total of 10 SES along the Highway 27 and the
      Gardiner Expressway of the city of Toronto. The results of the before-and-after
      study revealed that there was not enough evidence to suggest that these signs
      have any impact on road safety along the adjacent roadway sections at a 95%
      confidence interval. The same results were obtained by comparing collisions that
      occurred during daylight and artificial light.

PMID- 24682166
TI  - Status of road safety and injury burden: India.

PMID- 24682167
TI  - [Multimorbidity of neurological patients in palliative care units].
AB  - BACKGROUND: Multimorbidity in patients with neurological diseases needs enhanced
      attention. Especially the treatment with medication for comorbidities should be
      regularly evaluated and adapted to the current condition of the patient. PROBLEM:
      The problem of how to deal with multimorbidity of neurological patients on
      palliative care units is discussed. MATERIAL AND METHODS: This article gives a
      retrospective review of data and presentation of own results together with a
      discussion on basic knowledge and expert recommendations. RESULTS: Multimorbidity
      of patients with neurological diseases depends on the underlying disease and age.
      Multimorbidity is often associated with polypharmacy which should be critically
      evaluated during palliative care treatment. Long-term pharmacological treatment
      often needs to be terminated as the side effects outweigh the benefits. Our own
      data show that patients leaving the palliative care unit often have a reduced
      amount of drugs compared to those who have died. Multimorbidity at the end of
      life includes dementia, delirium and epileptic seizures as well as symptoms
      associated with tube feeding. Artificial nutrition should be regarded as a form
      of pharmacological treatment and its usefulness at the end of life carefully
      evaluated.

PMID- 24682168
TI  - [CXCL13: a biomarker for acute Lyme neuroborreliosis: investigation of the
      predictive value in the clinical routine].
AB  - BACKGROUND: The level of CXCL13 is a cerebrospinal fluid (CSF) biomarker for
      acute Lyme neuroborreliosis (LNB) with a high sensitivity. As the concentration
      rapidly declines during antibiotic therapy CXCL13 can also be used as a follow-up
      parameter. However, CXCL13 is not yet in use as a routine parameter due to
      concerns about the specificity. OBJECTIVES: The sensitivity, specificity and
      predictive value of CXCL13 in the clinical routine work-up of suspected LNB was
      analyzed. MATERIAL AND METHODS: Since July 2010 the CSF of all patients (n = 204)
      with suspected acute LNB was not only analyzed for the routine parameters (i.e.
      pleocytosis and intrathecal production of Borrelia-specific antibodies, AI) but
      also for CXCL13. In cases of incongruent findings, a follow-up puncture after
      antibiotic therapy was carried out. The cut-off level for acute LNB was set at
      250 pg/ml. RESULTS: This study included 179 patients who were not pretreated with
      antibiotics. Of these patients 15 suffered from definite LNB, 3 had a probable
      LNB and all had a CXCL13 value above the cut-off level. Only 2 of the 161
      patients with a non-LNB diagnosis (both with a lymphoma) had a CXCL13 value in
      the CSF higher than 250 pg/ml. Especially noteworthy were two patients without
      pleocytosis in the CSF but with CXCL13 levels above the cut-off level in whom LNB
      could be confirmed in the follow-up CSF analysis. CONCLUSIONS: The biomarker
      CXCL13 has a higher sensitivity (100 % vs. 87 %) with a specificity (99 %)
      comparable with the established diagnostic markers for LNB, e.g. CSF pleocytosis
      and Borrelia-AI in the investigated patient population. The negative predictive
      value of CXCL13 is 100 %. Therefore, a normal CXCL13 level virtually excludes
      LNB. In the clinical routine CXCL13 is a valuable and practical diagnostic marker
      for LNB and can even detect an acute LNB in patients without CSF pleocytosis.

PMID- 24682169
TI  - [Cluster-like headache due to dissection of the internal carotid artery after
      Pilates training].

PMID- 24682170
TI  - [Development of neurology in Germany after 1960].

PMID- 24682173
TI  - Overcoming Challenges in the Management of Critical Events During Cardiopulmonary
      Bypass.
AB  - Critical events during cardiopulmonary bypass (CPB) can challenge the most
      experienced perfusionists, anesthesiologists, and surgeons and can potentially
      lead to devastating outcomes. Much of the challenge of troubleshooting these
      events requires a key understanding of these situations and a well-defined
      strategy for early recognition and treatment. Adverse situations may be
      anticipated prior to going on CPB. Atherosclerosis is pervasive, and a high
      plaque burden may have implications in surgical technique modification and
      planning of CPB. Hematologic abnormalities such as cold agglutinins, antithrombin
      III deficiency, and hemoglobin S have been discussed with emphasis on managing
      complications arising from their altered pathophysiology. Jehovah's witness
      patients require appropriate techniques for cell salvage to minimize blood loss.
      During initiation of CPB, devastating situations leading to acute hypoperfusion
      and multiorgan failure may be encountered in patients undergoing surgery for
      aortic dissection. Massive air emboli during CPB, though rare, necessitate an
      urgent diagnosis to detect the source and prompt management to contain
      catastrophic outcomes. Gaseous microemboli remain ubiquitous and continue to be a
      major concern for neurocognitive impairment despite our best efforts to improve
      techniques and refine the CPB circuit. During maintenance of CPB, adverse events
      reflect inability to provide optimal perfusion and can be ascribed to CPB machine
      malfunction or physiological aberrations. We also discuss critical events that
      can occur during perfusion and the need to monitor for organ perfusion in altered
      physiologic states emanating from hemodilution, hypothermia, and acid-base
      alterations. 

PMID- 24682174
TI  - A novel mild variant of osteogenesis imperfecta type I caused by a Gly1088Glu
      mutation in COL1A1.
AB  - Osteogenesis imperfecta (OI), also known as brittle bone disease, characterized
      by multiplicative osteopsathyrosis, blue sclera, dentinogenesis imperfecta and
      mild audition, is a rare inherited connective tissue disease. There are seven
      types of OI, I to VII, among which type I-IV are relatively common and associated
      with type I collagen. Defects in type I collagen synthesis or structure are
      responsible for the majority of clinical OI cases since collagen is the major
      matrix protein of all connective tissues. Type I collagen consists of two pro
      alpha1 chains and one pro-alpha2 chain, which are encoded by two genes, COL1A1
      and COL1A2, respectively. The two subunits have a Gly-X-Y repeat domain, of which
      glycine is highly conserved in the majority of species. Point mutations on these
      sites appear to trigger OI. In the current study, a heterozygous mutation,
      c.3263G>A, p.Gly1088Glu, was identified in the Gly-X-Y domain of type I collagen
      in an affected individual with type I OI. A lethal phenotype with the
      p.Gly1088Ala mutation was observed at the same site as the current findings. This
      suggests that variant characteristics of the substitution for Gly may trigger a
      varying degree of OI from lethal to mild, even when the mutation occurs at the
      same site. It is hypothesized that the study may provide insight into the
      phenotype-genotype association and may assist, not only in the clinical
      diagnosis, but also in investigating the mechanism of collagen-associated
      diseases.

PMID- 24682171
TI  - A high-affinity protein binder that blocks the IL-6/STAT3 signaling pathway
      effectively suppresses non-small cell lung cancer.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune
      responses for host defense and tumorigenic process. Upregulation of IL-6 is known
      to constitutively phosphorylate signal transducer and activator of transcription
      3 (STAT3), leading to activation of multiple oncogene pathways and inflammatory
      cascade. Here, we present the development of a high-affinity protein binder,
      termed repebody, which effectively suppresses non-small cell lung cancer in vivo
      by blocking the IL-6/STAT3 signaling. We selected a repebody that prevents human
      IL-6 (hIL-6) from binding to its receptor by a competitive immunoassay, and
      modulated its binding affinity for hIL-6 up to a picomolar range by a modular
      approach that mimics the combinatorial assembly of diverse modules to form
      antigen-specific receptors in nature. The resulting repebody was highly specific
      for hIL-6, effectively inhibiting the STAT3 phosphorylation in a dose- and
      binding affinity-response manner in vitro. The repebody was shown to have a
      remarkable suppression effect on the growth of tumors and STAT3 phosphorylation
      in xenograft mice with non-small cell lung cancer by blocking the hIL-6/STAT3
      signaling. Structural analysis of the repebody and IL-6 complex revealed that the
      repebody binds the site 2a of hIL-6, overlapping a number of epitope residues at
      site 2a with gp130, and consequently causes a steric hindrance to the formation
      of IL-6/IL-6Ralpha complex. Our results suggest that high-affinity repebody
      targeting the IL-6/STAT3 pathway can be developed as therapeutics for non-small
      cell lung cancer. 

PMID- 24682172
TI  - Aptamer-targeted antigen delivery.
AB  - Effective therapeutic vaccines often require activation of T cell-mediated
      immunity. Robust T cell activation, including CD8 T cell responses, can be
      achieved using antibodies or antibody fragments to direct antigens of interest to
      professional antigen presenting cells. This approach represents an important
      advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising
      alternative to protein-based targeting approaches. We have selected aptamers that
      specifically bind the murine receptor, DEC205, a C-type lectin expressed
      predominantly on the surface of CD8alpha(+) dendritic cells (DCs) that has been
      shown to be efficient at facilitating antigen crosspresentation and subsequent
      CD8(+) T cell activation. Using a minimized aptamer conjugated to the model
      antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified
      in vitro and in vivo by proliferation and cytokine production by primary murine
      CD8(+) T cells expressing a T cell receptor specific for the major
      histocompatibility complex (MHC) I-restricted OVA257-264 peptide SIINFEKL.
      Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205
      aptamer-OVA-mediated antigen delivery stimulated strong proliferation and
      production of interferon (IFN)-gamma and interleukin (IL)-2. The immune responses
      elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of
      established OVA-expressing B16 tumor cells. Our results demonstrate a new
      application of aptamer technology for the development of effective T cell
      mediated vaccines. 

PMID- 24682176
TI  - Fe-Catalysed oxidative C-H/N-H coupling between aldehydes and simple amides.
AB  - A novel oxidative coupling of aldehydes with simple amides, most likely involving
      a radical process, was achieved through the use of an iron catalyst. Various
      amides were utilized as substrates to easily construct imides by coupling with
      aldehydes. A catalytic cycle involving the benzoyl halide intermediate is
      proposed based on our experimental results. 

PMID- 24682175
TI  - Latent period and transmission of "Candidatus Liberibacter solanacearum" by the
      potato psyllid Bactericera cockerelli (Hemiptera: Triozidae).
AB  - "Candidatus Liberibacter solanacearum" (Lso) is an economically important
      pathogen of solanaceous crops and the putative causal agent of zebra chip disease
      of potato (Solanum tuberosum L.). This pathogen is transmitted to solanaceous
      species by the potato psyllid, Bactericera cockerelli (Sulc), but many aspects of
      the acquisition and transmission processes have yet to be elucidated. The present
      study was conducted to assess the interacting effects of acquisition access
      period, incubation period, and host plant on Lso titer in psyllids, the movement
      of Lso from the alimentary canal to the salivary glands of the insect, and the
      ability of psyllids to transmit Lso to non-infected host plants. Following
      initial pathogen acquisition, the probability of Lso presence in the alimentary
      canal remained constant from 0 to 3 weeks, but the probability of Lso being
      present in the salivary glands increased with increasing incubation period. Lso
      copy numbers in psyllids peaked two weeks after the initial pathogen acquisition
      and psyllids were capable of transmitting Lso to non-infected host plants only
      after a two-week incubation period. Psyllid infectivity was associated with
      colonization of insect salivary glands by Lso and with Lso copy numbers >10,000
      per psyllid. Results of our study indicate that Lso requires a two-week latent
      period in potato psyllids and suggest that acquisition and transmission of Lso by
      psyllids follows a pattern consistent with a propagative, circulative, and
      persistent mode of transmission. 

PMID- 24682177
TI  - Different techniques for performing DALK: are they making a real difference?

PMID- 24682178
TI  - Timing of congenital dacryostenosis resolution and the development of
      anisometropia.
AB  - BACKGROUND: Anisometropia was recently shown to occur in 10% of infants diagnosed
      with dacryostenosis at a mean age of 1 year. The purpose of this study was to
      determine whether earlier (<1 year) spontaneous resolution or probing decreases
      the risk of anisometropia in infants with dacryostenosis. METHODS: The medical
      records of all patients diagnosed as infants with dacryostenosis at Mayo Clinic,
      Rochester, Minnesota, USA, from 1 January 1988 to 31 December 1992 were
      retrospectively reviewed. Of 662 consecutive infants diagnosed with
      dacryostenosis, 244 (36.9%) were subsequently examined in the ophthalmology
      department and included in the study. Each of the study patients was followed
      through to 30 June 2011. The main outcome measure was the rate of anisometropia
      (>=1 dioptre between the two eyes) among those who spontaneously resolved and
      those who underwent surgery. RESULTS: Among the 244 cases, 189 (77.5%)
      spontaneously resolved at a mean age of 4.5 months (range 0.3-35 months), and 55
      (22.5%) underwent surgery at a mean age of 16 months (range 0-53 months).
      Anisometropia was diagnosed in 17 (9.0%) of the 189 who spontaneously resolved
      and in 2 (3.6%) of the 55 operated children (p=0.19). Although there was no
      significant trend, earlier resolution was associated with higher rates of
      anisometropia. CONCLUSIONS: Early spontaneous resolution of dacryostenosis was
      more likely to have a higher, not lower, rate of anisometropia than late
      spontaneous or surgical resolution. Further studies are warranted to clarify the
      relationship between infantile dacryostenosis and the development of hyperopic
      anisometropia.

PMID- 24682179
TI  - Ophthalmic statistics note: the perils of dichotomising continuous variables.

PMID- 24682180
TI  - Improving the cost-effectiveness of photographic screening for diabetic macular
      oedema: a prospective, multi-centre, UK study.
AB  - BACKGROUND/AIMS: Retinal screening programmes in England and Scotland have
      similar photographic grading schemes for background (non-proliferative) and
      proliferative diabetic retinopathy, but diverge over maculopathy. We looked for
      the most cost-effective method of identifying diabetic macular oedema from
      retinal photographs including the role of automated grading and optical coherence
      tomography, a technology that directly visualises oedema. METHODS: Patients from
      seven UK centres were recruited. The following features in at least one eye were
      required for enrolment: microaneurysms/dot haemorrhages or blot haemorrhages
      within one disc diameter, or exudates within one or two disc diameters of the
      centre of the macula. Subjects had optical coherence tomography and digital
      photography. Manual and automated grading schemes were evaluated. Costs and QALYs
      were modelled using microsimulation techniques. RESULTS: 3540 patients were
      recruited, 3170 were analysed. For diabetic macular oedema, England's scheme had
      a sensitivity of 72.6% and specificity of 66.8%; Scotland's had a sensitivity of
      59.5% and specificity of 79.0%. When applying a ceiling ratio of L30,000 per
      quality adjusted life years (QALY) gained, Scotland's scheme was preferred.
      Assuming automated grading could be implemented without increasing grading costs,
      automation produced a greater number of QALYS for a lower cost than England's
      scheme, but was not cost effective, at the study's operating point, compared with
      Scotland's. The addition of optical coherence tomography, to each scheme,
      resulted in cost savings without reducing health benefits. CONCLUSIONS: Retinal
      screening programmes in the UK should reconsider the screening pathway to make
      best use of existing and new technologies.

PMID- 24682182
TI  - Blue light injures corneal epithelial cells in the mitotic phase in vitro.

PMID- 24682181
TI  - Outcome and quality of screening in a nationwide survey on retinopathy of
      prematurity in The Netherlands.
AB  - PURPOSE: Provide insight in natural history, screening and treatment policy of
      retinopathy of prematurity (ROP) in The Netherlands. METHODS: A multicentre,
      prospective, population-based study (NEDROP) included all preterm infants born in
      2009 in The Netherlands fulfilling the inclusion criteria for ROP screening.
      Anonymised data from ophthalmologists, neonatologists and paediatricians were
      merged on identification number. RESULTS: Of 2033 reported infants, 1688 (83%)
      were screened for ROP. ROP stage was reported in 100%, zone in 94.4% and plus
      disease in 83%. ROP developed in 324 (19.2%), mild ROP (stage 1-2) in 294
      (17.4%), severe ROP (stage 3 or more) in 30 (1.8%) and 17 (1%) were treated. The
      initial screening examination was not performed within the required 42 days in
      641 (38%). Date for follow-up was recorded 1973 times and accomplished within 3
      days from the planned date in 1957 (99.2%). The chance of not being screened
      increased from 12.9% without transfer to another hospital to 23.5, 18.5 and 25%
      after 1, 2, or 3 transfers, respectively. CONCLUSIONS: The incidence of severe
      ROP and infants treated was low. NEDROP emphasises that timing of initial
      examination and transfer to another hospital are issues of concern within the
      screening process.

PMID- 24682183
TI  - Photobiomodulation in the treatment of patients with non-center-involving
      diabetic macular oedema.
AB  - PURPOSE: Far-red/near-infrared phototherapy or photobiomodulation (PBM) has
      recently been reported to be an effective and non-invasive treatment method to
      inhibit lesions of diabetic retinopathy (DR) in animals. This study investigated
      the safety and efficacy of PBM in diabetic patients to treat non-center-involving
      diabetic macular oedema (NCDME). METHODS: This was a non-randomised, consecutive,
      case series, where 4 patients with type 2 diabetes with NCDME were treated for
      160 s per day with PBM for 2-9 months. Demographic data including age, sex,
      HbA1c%, electronic ETDRS visual acuity, and retinal and macular thickness were
      measured using spectral domain ocular coherence tomography (SD-OCT) before and
      after treatment. RESULTS: Four eyes of 4 patients were treated, with fellow eyes
      serving as untreated controls. Daily PBM treatment for only 80 s per treatment
      twice daily caused a significant reduction in focal retinal thickening in all 4
      treated eyes. No adverse effects attributable to therapy were noted by the
      patients or study investigators during the study period. CONCLUSIONS: PBM
      potentially offers a non-invasive and cost-effective therapeutic option for
      patients with NCDME. Further studies of this therapeutic option in DR are
      warranted.

PMID- 24682184
TI  - Prevalence and aetiology of ocular hypertension in acute and chronic uveitis.
AB  - AIMS: To evaluate the prevalence and aetiology of intraocular hypertension (OHT)
      in granulomatous and non-granulomatous uveitis METHODS: Medical records of 304
      consecutive patients (484 eyes) with uveitis who visited the National Defense
      Medical Collage Hospital between April 2010 and March 2013 were reviewed
      retrospectively. OHT irrelevant to glaucomatous changes in optic disc or visual
      field was investigated. RESULTS: OHT was found in 123 eyes (25.4%) of 93 uveitic
      patients (30.6%); 92% of the eyes had open-angle OHT, 45.6% of which was steroid
      induced. The prevalence of OHT was 100% (8/8) in Posner-Schlossman syndrome,
      50.0% (10/20) in varicella zoster virus-associated iridocyclitis, 45% (9/20) in
      scleritis, 34.1% (15/44) in Vogt-Koyanagi-Harada disease, 32.1% (18/56) in
      Behcet's disease (BD), 23.1% (6/26) in acute anterior uveitis, and 20.2% (19/94)
      in sarcoidosis. Pupillary block was observed only in non-granulomatous uveitis,
      but not in granulomatous uveitis. Seventy percent of OHT in granulomatous uveitis
      cases was inflammation-induced, while 76.7% in non-granulomatous uveitis cases
      was steroid-induced. CONCLUSIONS: OHT in non-granulomatous uveitis was mainly
      steroid-induced open-angle OHT with some cases of angle-closure OHT caused by
      pupillary block, while that in granulomatous uveitis was mostly inflammation
      induced open-angle OHT with no pupillary block-related angle-closure OHT.

PMID- 24682185
TI  - Texaphyrin sensitized near-IR-to-visible photon upconversion.
AB  - Near-IR (NIR) absorption from a Cd(ii) texaphyrin (TXP) has been successfully
      coupled with rubrene triplet acceptors/annihilators in vacuum degassed
      dichloromethane to upconvert NIR (670-800 nm) incident photons into yellow
      fluorescence through sensitized triplet-triplet annihilation. Stern-Volmer
      analysis of dynamic energy transfer quenching of TXP by rubrene using transient
      absorption spectroscopy revealed Stern-Volmer and bimolecular quenching constants
      of 21,000 M(-1) and 5.7 * 10(8) M(-1) s(-1) respectively, for the triplet-triplet
      energy transfer process. The upconverted emission intensity with respect to the
      incident excitation power density at 750 nm was shown to vary between quadratic
      and linear, illustrating the expected kinetic limits for the light producing
      photochemistry under continuous wave illumination. Furthermore, with increasing
      TXP sensitizer concentration, the characteristic quadratic-to-linear crossover
      point shifted to lower incident photon power density. This is consistent with the
      notion that stronger photon capture in the sensitizer leads to experimental
      conditions promoting upconversion under milder excitation conditions. The maximum
      quantum yield of the TXP-sensitized rubrene upconverted fluorescence was 1.54 +/-
      0.04% under dilute conditions determined relative to [Os(phen)3](PF6)2 under
      continuous wave excitation conditions. This saturating quantum efficiency was
      realized when the incident light power dependence reached the quadratic-to-linear
      crossover point and was constant over the region where the composition displayed
      linear response to incident light power density. In pulsed laser experiments at
      higher sensitizer concentrations, the triplet-triplet annihilation quantum yield
      was determined to saturate at approximately 13%, corresponding to an upconversion
      yield of ~10%, suggesting that the dichloromethane solvent either lowers the T2
      state of the rubrene acceptor or is somehow attenuating the annihilation reaction
      between excited rubrene triplets.

PMID- 24682188
TI  - Recurrent pregnancy loss and thrombophilia.

PMID- 24682187
TI  - Expertise Effects in Face-Selective Areas are Robust to Clutter and Diverted
      Attention, but not to Competition.
AB  - Expertise effects for nonface objects in face-selective brain areas may reflect
      stable aspects of neuronal selectivity that determine how observers perceive
      objects. However, bottom-up (e.g., clutter from irrelevant objects) and top-down
      manipulations (e.g., attentional selection) can influence activity, affecting the
      link between category selectivity and individual performance. We test the
      prediction that individual differences expressed as neural expertise effects for
      cars in face-selective areas are sufficiently stable to survive clutter and
      manipulations of attention. Additionally, behavioral work and work using event
      related potentials suggest that expertise effects may not survive competition; we
      investigate this using functional magnetic resonance imaging. Subjects varying in
      expertise with cars made 1-back decisions about cars, faces, and objects in
      displays containing one or 2 objects, with only one category attended. Univariate
      analyses suggest car expertise effects are robust to clutter, dampened by
      reducing attention to cars, but nonetheless more robust to manipulations of
      attention than competition. While univariate expertise effects are severely
      abolished by competition between cars and faces, multivariate analyses reveal new
      information related to car expertise. These results demonstrate that signals in
      face-selective areas predict expertise effects for nonface objects in a variety
      of conditions, although individual differences may be expressed in different
      dependent measures depending on task and instructions. 

PMID- 24682186
TI  - Validity of myocardial infarction diagnoses in administrative databases: a
      systematic review.
AB  - BACKGROUND: Though administrative databases are increasingly being used for
      research related to myocardial infarction (MI), the validity of MI diagnoses in
      these databases has never been synthesized on a large scale. OBJECTIVE: To
      conduct the first systematic review of studies reporting on the validity of
      diagnostic codes for identifying MI in administrative data. METHODS: MEDLINE and
      EMBASE were searched (inception to November 2010) for studies: (a) Using
      administrative data to identify MI; or (b) Evaluating the validity of MI codes in
      administrative data; and (c) Reporting validation statistics (sensitivity,
      specificity, positive predictive value (PPV), negative predictive value, or Kappa
      scores) for MI, or data sufficient for their calculation. Additonal articles were
      located by handsearch (up to February 2011) of original papers. Data were
      extracted by two independent reviewers; article quality was assessed using the
      Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: Thirty studies
      published from 1984-2010 were included; most assessed codes from the
      International Classification of Diseases (ICD)-9th revision. Sensitivity and
      specificity of hospitalization data for identifying MI in most [>=50%] studies
      was >=86%, and PPV in most studies was >=93%. The PPV was higher in the more
      recent studies, and lower when criteria that do not incorporate cardiac troponin
      levels (such as the MONICA) were employed as the gold standard. MI as a cause-of
      death on death certificates also demonstrated lower accuracy, with maximum PPV of
      60% (for definite MI). CONCLUSIONS: Hospitalization data has higher validity and
      hence can be used to identify MI, but the accuracy of MI as a cause-of-death on
      death certificates is suboptimal, and more studies are needed on the validity of
      ICD-10 codes. When using administrative data for research purposes, authors
      should recognize these factors and avoid using vital statistics data if
      hospitalization data is not available to confirm deaths from MI.

PMID- 24682189
TI  - Antioxidant potential of green leafy porridges.
AB  - OBJECTIVES: To evaluate the antioxidant potential of porridges (kola kenda) made
      incorporating herbs. DESIGN: Experimental study. Main outcome measures Total
      phenolic content was estimated by Folin Ciocalteau method (GAEmg/g(FW) and the
      antioxidant potential by ABTS free radical scavenging activity (TEAC(MUg)/100g
      (FW). RESULTS: Total phenolics and antioxidant potentials of porridges ranged
      from 5-73 TEAC(MUg) /100g and 0.9- 34.2 GAEg/100g respectively. Significantly
      high (p <= 0.05) total phenolic contents were observed in C. auriculata
      ("Ranawara") [342 GAE mg/g (FW)] and in M. koenigii ("Karapincha") [199
      GAEmg/g(FW)]. The highest antioxidant effect was in C. auriculata ("Ranawara")
      [73 TEAC(MUg)/100g(FW)] followed by M. koenigi ("Karapincha") [26 TEAC(MUg)/100g
      (FW)] and C. ternatea ("Ela Katarolu") [24 TEAC(MUg)/100g (FW)]. Lowest
      antioxidant effect was in porridges made with rice and coconut milk both of which
      had comparable values. A positive correlation (correlation coefficient > 0.8)
      between total phenolics and the antioxidant potential was observed for all
      porridges except for Asparagus racemosus (Haathawariya) porridge which had a high
      antioxidant potential with a low phenolic content. CONCLUSIONS: This study
      provides evidence that green leafy porridges are a good source of antioxidants in
      addition to their reported low glycaemic indices.

PMID- 24682190
TI  - Validity of the Sinhala version of the centre for epidemiological studies
      depression scale (CES-D) in out-patients.
AB  - OBJECTIVES: To translate and validate the Sinhala version of the Centre for
      Epidemiological Studies Depression scale (CES-D) for diagnosing depression in out
      patients. DESIGN: A combined qualitative and quantitative approach was used for
      the translation of the CES-D. Sample size was calculated to detect a targeted
      sensitivity and specificity of 85%. The sample consisted of 75 participants
      diagnosed with major depressive disorder according to DSM IV criteria and 75
      gender matched controls. Criterion validity was assessed using receiver operating
      charact-eristic (ROC) analysis. The Structured Clinical Interview for DSM-IV
      (SCID-II) conducted by a psychiatrist was used as the gold standard. RESULTS:
      Mean age of the sample was 33 years. There were 91 females (60.7%). There was
      significant difference in the mean CES-D scores between cases (13.94) and
      controls (6.58) [t=14.50, df=148, p<0.001]. A score of >= 16 gave a sensitivity
      of 84% and specificity of 92%. A score of >= 21 gave a sensitivity of 73.3% and
      specificity of 96%. The Cronbach's alpha was 0.93. The four items that were
      reverse coded had poor correlation with total scores. The average correlation
      coefficient for the reverse-scored items was 0.35 and for the rest of the items
      0.63. Principal component analysis with oblique rotation identified four factors.
      Factor 1 corresponds to the "depressed affect" and "somatic complaints" in the
      original model proposed by Radloff. Factor 2 corresponds to the interpersonal
      concerns. Factors 3 and 4 loaded the reversed coded items. CONCLUSIONS: The
      Sinhala version of the CES-D is a valid and reliable instrument for diagnosing
      major depressive disorder.

PMID- 24682191
TI  - Adherence to preventive health care in children and young adults with Down
      syndrome (DS) in Sri Lanka.
AB  - OBJECTIVES: To assess adherence to preventive care and age-appropriate screening
      in different age categories of Down syndrome (DS) persons. METHODS: This
      community-based retrospective observational study on ambulatory persons with DS
      from different regions of Sri Lanka was carried out on 100 randomly selected
      individuals from a sample framework of approximately 300. Their screening
      behavior for cardiac, ophthalmic, hearing and thyroid status was evaluated. Age
      at first medical consultation for DS specific complications, whether undertaken
      when symptomatic or asymptomatic, and use of DS-specific growth charts were
      extracted from medical records. Screening was compared in three age groups (<10,
      10-15, and >15 years). RESULTS: One hundred clinically diagnosed DS individuals
      (F: M 1:1.2) aged 2-28 years (mean 13.5 years) were from varied socio-economic
      backgrounds and rural (68%) suburban (20%) and urban (12%) settings. They all had
      had postnatal medical assessments. Initial eye, ENT, cardiac consultations was at
      significantly earlier ages in those below 10 years. Age-appropriate cardiac
      assessments occurred in 58%, 25% and 7.5% in each age group. Vision, hearing and
      newborn thyroid status were not routinely screened for. Only 7% had special
      growth charts. Area of residence had no effect on screening behavior.
      CONCLUSIONS: Screening for complications in DS was delayed and inconsistent but
      occurred at significantly earlier ages in younger children. Use of appropriate
      growth charts was very low. Screening behavior was unaffected by area of
      residence. We recommend incorporating DS-specific medical checklists as a
      preventive health routine for this unique group of children.

PMID- 24682192
TI  - Incidence of inflammatory bowel disease in Gampaha district: details of the Sri
      Lankan component of the Asia-Pacific Crohn's and colitis epidemiology study.
AB  - The aim of this report is to provide details of the methodology and results of
      the Sri Lankan component of the Asia-Pacific Crohn's and Colitis Epidemiology
      Study. Fourteen state and private hospitals with specialist services in the
      Gampaha and Colombo districts were kept under surveillance over a 12 month period
      to recruit patients with newly diagnosed Inflammatory Bowel Disease (IBD) who
      were permanent residents of the Gampaha district. Thirty five cases (ulcerative
      colitis-21, Crohn's disease-13, IBD-undetermined-1) were detected, giving a crude
      annual IBD incidence of 1.59 per 100,000 population. 

PMID- 24682193
TI  - Periodontal status of type I diabetics compared to non-diabetic participants: a
      preliminary study.
AB  - A preliminary group matched comparison study of periodontal status was conducted
      among Indian participants who had type 1 diabetes mellitus (T1DM) and non
      diabetic controls. The mean number of bleeding sites, gigival index score, number
      of periodontal pocket's and number of clinical loss attachment sites were all
      significantly higher in cases compared to controls. This study provides evidence
      that people with type I diabetes mellitus have a higher risk of gingival and
      periodontal disease. 

PMID- 24682194
TI  - Relationship between increased risk of falling and cognitive impairment in
      residents of an elderly home in the Colombo district.
AB  - Tendency to falling in older people, with and without cognitive impairment,
      living in an elderly home was assessed. A descriptive analytical study was
      carried out with 50 elderly people (25 males) aged between 60 - 85 years. Timed
      Up and Go (TUG) test and, Five Times Sit to Stand Test (FTSST) were used to
      determine risk of falling and functional lower extremity strength of each
      participant. The Folstein Mini Mental State Examination (MMSE) and Montreal
      Cognitive Assessment (MoCA) were used to assess cognition.The cognitive scores
      were significantly lower in fallers compared to non-fallers (p=0.0001). Fallers
      demonstrated significantly poor lower extremity strength (p=0.0001). Older people
      with cognitive impairment demonstrated poor functional lower extremity strength
      than those without cognitive impairement (p=0.002). The difference in falling
      tendency between males and females was not statistically significant. 

PMID- 24682195
TI  - A characteristic cutaneous lesion over the sting site of the wasp, Vespa tropica.

PMID- 24682196
TI  - Mosapride (5HT4 agonist) in the treatment of blepharospasm.

PMID- 24682198
TI  - Thrombotic microangiopathy following Russell's viper (Daboia russelii) envenoming
      in Sri Lanka: a case report.

PMID- 24682197
TI  - A case of Hb Hofu in Sri Lanka.

PMID- 24682199
TI  - Benign intracranial hypertension following vitamin A megadose.

PMID- 24682200
TI  - Should the judicial medical officer (JMO) discuss the cause and manner of death
      with the family of the deceased?

PMID- 24682201
TI  - Culture and immunochromatographic technique for diagnosis of trichomoniasis.

PMID- 24682202
TI  - Moonlight detection by Drosophila's endogenous clock depends on multiple
      photopigments in the compound eyes.
AB  - Many organisms change their activity on moonlit nights. Even the fruit fly
      Drosophila melanogaster responds to moonlight with a shift of activity into the
      night, at least under laboratory conditions. The compound eyes have been shown to
      be essential for the perception of moonlight, but it is unknown which of the 5
      rhodopsins in the eyes are responsible for the observed moonlight effects. Here,
      we show that the outer (R1-R6) and inner (R7 and R8) photoreceptor cells in a
      fly's ommatidium interact in a complex manner to provoke the moonlight effects on
      locomotor activity. The shift of the evening activity peak into the night depends
      on several rhodopsins in the inner and outer photoreceptor cells. The increase in
      relative nocturnal activity in response to moonlight is mainly mediated by the
      rhodopsin 6-expressing inner photoreceptor cell R8 together with the rhodopsin 1
      expressing outer receptor cells (R1-R6), whereas just rhodopsin 1 of R1 to R6
      seems necessary for increasing nocturnal activity in response to increasing
      daylight intensity. 

PMID- 24682203
TI  - HSP90 affects the stability of BMAL1 and circadian gene expression.
AB  - The mammalian circadian clock comprises a system of interconnected
      transcriptional and translational feedback loops. Proper oscillator function
      requires the precisely timed synthesis and degradation of core clock proteins.
      Heat shock protein 90 (HSP90), an adenosine triphosphate (ATP)-dependent
      molecular chaperone, has important functions in many cellular regulatory pathways
      by controlling the activity and stability of its various client proteins. Despite
      accumulating evidence for interplay between the heat shock response and the
      circadian system, the role of HSP90 in the mammalian core clock is not known. The
      results of this study suggest that inhibition of the ATP-dependent chaperone
      activity of HSP90 impairs circadian rhythmicity of cultured mouse fibroblasts
      whereby amplitude and phase of the oscillations are predominantly affected.
      Inhibition of HSP90 shortened the half-life of BMAL1, which resulted in reduced
      cellular protein levels and blunted expression of rhythmic BMAL1-CLOCK target
      genes. Furthermore, the HSP90 isoforms HSP90AA1 and HSP90AB1, and not HSP90B1
      GRP94 or TRAP1, are responsible for maintaining proper cellular levels of BMAL1
      protein. In summary, these findings provide evidence for a model in which
      cytoplasmic HSP90 is required for transcriptional activation processes by the
      positive arm of the mammalian circadian clock. 

PMID- 24682204
TI  - Effects of the duper mutation on responses to light: parametric and nonparametric
      responses, range of entrainment, and masking.
AB  - The duper mutation in Syrian hamsters shortens the free-running period (tauDD) of
      locomotor activity by approximately 1 h when expressed on the wild-type
      background and by 2 h on the tau mutant background ("super duper"). In either
      case, duper markedly amplifies the phase response curve (PRC) of the light pulse.
      This work examined whether the duper mutation alters parametric as well as
      nonparametric properties, intensity thresholds, and noncircadian responses to
      light. Furthermore, it assessed the effects of duper on the range of entrainment
      and circadian aftereffects. In the first study, duper mutant and wild-type (wt)
      hamsters showed a similar intensity threshold for light-induced phase shifts. In
      the second, wt, tau mutant, and super duper hamsters were exposed to LD cycles
      whose period (T) progressively shortened. Regardless of whether the light phase
      was held at 50% of T or fixed at 3 h, super duper mutants entrained to a wider
      range of T cycles and showed aftereffects upon release into DD. In the third
      study, tauLL was measured in mutant and wt hamsters that were maintained for 30
      day intervals in constant light of progressively greater intensities. With
      increasing light intensity, the circadian period shortened in duper mutants.
      Circadian rhythms of super duper hamsters were disrupted at light intensities
      considerably below those that induced arrhythmicity in wt, tau heterozygote, or
      duper homozygote hamsters. In the fourth study, hamsters that were wt or
      homozygous for duper received two 15-min light pulses: the first at CT14 to CT16
      or CT17 to CT19 and the second 2 h later. As expected, wt and duper mutants
      showed weak and strong resetting, respectively. Light pulses in early subjective
      night had an additive effect in mutant but not in wt hamsters, indicating that
      larger phase shifts of the pacemaker take longer to complete. Finally, super
      duper hamsters showed slightly but not significantly more negative masking than
      did wt or duper mutant hamsters. These results indicate that the duper mutation
      affects the properties of the central circadian pacemaker. The mutant allele
      affects not only the PRC but also parametric responses to light. 

PMID- 24682205
TI  - The Tau mutation of casein kinase 1epsilon sets the period of the mammalian
      pacemaker via regulation of Period1 or Period2 clock proteins.
AB  - The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian
      pacemaker in mammals, coordinating daily metabolic and physiological rhythms with
      the cycle of sleep and wakefulness. SCN neurons define circadian time via an auto
      regulatory feedback loop in which the activation of Period (Per) and Cryptochrome
      genes is periodically suppressed by their own protein products. Casein kinase 1
      (CK1) enzymes have a critical role in circadian pacemaking because they
      phosphorylate PER proteins and thereby direct their proteasomal degradation. In
      human pedigrees, individual mutations in either hCK1 or hPER2 lead to advanced
      sleep phase disorders, whereas in rodents, the Tau mutation of CK1 epsilon
      (CK1epsilon (Tau)) accelerates rest-activity cycles and shortens the period of
      the SCN molecular pacemaker. Biochemical analyses of recombinant PER proteins in
      cultured cells and endogenous proteins in peripheral tissues have identified PER1
      and PER2, but not PER3, as direct substrates of CK1epsilon. The purpose of this
      study, therefore, was to determine the relative contributions of endogenous PER
      proteins to the period-accelerating effects of CK1epsilon (Tau), both in vivo and
      in vitro. CK1epsilon (Tau) mice were mated onto Per1-, Per2-, and Per1-Per2
      (Per1/2) double-null backgrounds, in all cases carrying the Per1-luciferase
      bioluminescent circadian reporter gene. Mice lacking both PER1 and PER2 were
      behaviorally arrhythmic, confirming the inadequacy of PER3 as a circadian factor.
      Individual loss of either PER1 or PER2 had no significant effect on the circadian
      period or quality of wheel-running behavior, and CK1epsilon (Tau) accelerated
      behavioral rhythms in both Per1- and Per2-null mice. CK1epsilon (Tau) also
      accelerated in vitro molecular pacemaking in SCN lacking either PER1 or PER2,
      with a greater effect in PER2-dependent (i.e., Per1-null) SCN than in PER1
      dependent slices. In double-null slices, some SCN were arrhythmic, whereas others
      exhibited transient rhythms, which trended nonsignificantly toward a shorter
      period. Both short-period and long-period rhythms could be identified in
      individual SCN neurons imaged by charge-coupled device camera. CK1epsilon (Tau)
      had no effect, however, on SCN-level or individual neuronal rhythms in the
      absence of PER1 and PER2. Thus, the CK1epsilon (Tau) allele has divergent
      actions, acting via both endogenous PER1 and PER2, but not PER3 protein, to
      mediate its circadian actions in vivo. Moreover, PER-independent cellular
      oscillations may contribute to pacemaking, but they are unstable and imprecise,
      and are not affected by the Tau mutation.

PMID- 24682206
TI  - Insights into behavioral vulnerability to differential sleep pressure and
      circadian phase from a functional ADA polymorphism.
AB  - Sleep loss affects human behavior in a nonuniform manner, depending on the
      cognitive domain and also the circadian phase. Besides, evidence exists about
      stable interindividual variations in sleep loss-related performance impairments.
      Despite this evidence, only a few studies have considered both circadian phase
      and neurobehavioral domain when investigating trait-like vulnerability to sleep
      manipulation. By applying a randomized, crossover design with 2 sleep pressure
      conditions (40 h sleep deprivation vs. 40 h multiple naps), we investigated the
      influence of a human adenosine deaminase (ADA) polymorphism (rs73598374) on
      several behavioral measures throughout nearly 2 circadian cycles. Confirming
      earlier studies, we observed that under sleep deprivation the previously reported
      vulnerable G/A-allele carriers felt overall sleepier than G/G-allele carriers. As
      expected, this difference was no longer present when sleep pressure was reduced
      by the application of multiple naps. Concomitantly, well-being was worse in the
      G/A genotype under sleep loss when compared to the nap protocol, and n-back
      working memory performance appeared to be specifically susceptible to sleep-wake
      manipulation in this genotype. When considering psychomotor vigilance
      performance, however, a higher sensitivity to sleep-wake manipulation was
      detected in homozygous participants, but specifically at the end of the night and
      only for optimal task performance. Although these data are based on a small
      sample size and hence require replication (12 G/A- and 12 G/G-allele carriers),
      they confirm the assumption that interindividual differences regarding the effect
      of sleep manipulation highly depend on the cognitive task and circadian phase,
      and thus emphasize the necessity of a multimethodological approach. Moreover,
      they indicate that napping might be suitable to counteract endogenously
      heightened sleep pressure depending on the neurobehavioral domain.

PMID- 24682207
TI  - Effects of caffeine on skin and core temperatures, alertness, and recovery sleep
      during circadian misalignment.
AB  - Caffeine promotes wakefulness during night shift work, although it also disturbs
      subsequent daytime sleep. Increased alertness by caffeine is associated with a
      higher core body temperature (CBT). A lower CBT and a narrow distal-to-proximal
      skin temperature gradient (DPG) have been reported to be associated with improved
      sleep, yet whether caffeine influences the DPG is unknown. We tested the
      hypothesis that the use caffeine during nighttime total sleep deprivation would
      reduce the DPG, increase CBT and alertness, and disturb subsequent daytime
      recovery sleep. We also expected that a greater widening of the DPG prior to
      sleep would be associated with a greater degree of sleep disturbance. Thirty
      healthy adults (9 females) aged 21.6 +/- 3.5 years participated in a double
      blind, 28-h modified constant routine protocol. At 23 h of wakefulness,
      participants in the treatment condition (n = 10) were given 2.9 mg/kg caffeine,
      equivalent to ~200 mg (or 2 espressos) for a 70-kg adult, 5 h before a daytime
      recovery sleep episode. Throughout the protocol, core and skin body temperatures,
      DPG, sleep architecture, and subjective alertness and mood were measured. Prior
      to sleep, caffeine significantly widened the DPG and increased CBT, alertness,
      and clear-headedness (p < 0.05). Caffeine also disturbed daytime recovery sleep
      (p < 0.05). Increased CBT and a wider DPG prior to sleep were associated with a
      longer latency to sleep, and a wider DPG was associated with disturbed recovery
      sleep (i.e., increased wakefulness after sleep onset, increased stage 1 sleep,
      decreased sleep efficiency, and decreased slow wave sleep) (p < 0.05). A widening
      of the DPG following nighttime caffeine may represent a component of the
      integrated physiological response by which caffeine improves alertness and
      disturbs subsequent daytime recovery sleep. Furthermore, our findings highlight
      that sleep disturbances associated with caffeine consumed near the circadian
      trough of alertness are still present when daytime recovery sleep occurs 5 h or
      approximately 1 half-life later. 

PMID- 24682208
TI  - Celestial orientation with the sun not in view: lizards use a time-compensated
      sky polarization compass.
AB  - The present investigation was aimed at testing whether the lizard sky
      polarization compass is time compensated. For this purpose, ruin lizards,
      Podarcis sicula, were both trained and tested for orientation inside a Morris
      water maze under clear skies with the sun not in view. During training, lizards
      showed a striking bimodal orientation along the training axis, demonstrating
      their capability of determining the symmetry plane of the sky polarization
      pattern and thus the use of polarization information in orientation. After
      reaching criteria, lizards were kept 7 days in a 6-h fast clock-shift treatment
      and then released with the sun not in view. Six-hour clock-shifted lizards showed
      a bimodal distribution of directional choices, which was oriented perpendicularly
      to the training axis, as it was expected on the basis of the clock-shift. The
      results show that the only celestial diurnal compass mechanism that does not need
      a direct vision of the sun disk (i.e., the sky polarization compass) is a time
      compensated compass. 

PMID- 24682209
TI  - A near complete snapshot of the Zea mays seedling transcriptome revealed from
      ultra-deep sequencing.
AB  - RNA-sequencing (RNA-seq) enables in-depth exploration of transcriptomes, but
      typical sequencing depth often limits its comprehensiveness. In this study, we
      generated nearly 3 billion RNA-Seq reads, totaling 341 Gb of sequence, from a Zea
      mays seedling sample. At this depth, a near complete snapshot of the
      transcriptome was observed consisting of over 90% of the annotated transcripts,
      including lowly expressed transcription factors. A novel hybrid strategy
      combining de novo and reference-based assemblies yielded a transcriptome
      consisting of 126,708 transcripts with 88% of expressed known genes assembled to
      full-length. We improved current annotations by adding 4,842 previously
      unannotated transcript variants and many new features, including 212 maize
      transcripts, 201 genes, 10 genes with undocumented potential roles in seedlings
      as well as maize lineage specific gene fusion events. We demonstrated the power
      of deep sequencing for large transcriptome studies by generating a high quality
      transcriptome, which provides a rich resource for the research community.

PMID- 24682210
TI  - Does change in cognitive function predict change in costs of care for people with
      a schizophrenia diagnosis following cognitive remediation therapy?
AB  - BACKGROUND AND AIMS: Schizophrenia leads to significant personal costs matched by
      high economic costs. Cognitive function is a strong predictor of disabilities in
      schizophrenia, which underpin these costs. This study of cognitive remediation
      therapy (CRT), which has been shown to improve cognition and reduce disability in
      schizophrenia, aims to investigate associations between improvements in cognition
      and cost changes. METHODS: Eighty-five participants with schizophrenia were
      randomized to receive CRT or treatment as usual and were assessed at baseline,
      posttherapy, and 6 month follow-up. Four structural equation models investigated
      associations between changes in cognitive function and costs of care. RESULTS:
      All 4 models provided a good fit. Improvement in 3 individual cognitive variables
      did not predict total cost changes (model 1). But improvement in a single latent
      cognition factor was associated with a reduction in depression, which in turn was
      associated with reduced subsequent total costs (model 2). No significant
      associations with constituent daycare and special accommodation cost changes were
      apparent with 3 individual cognitive change variables (model 3). But improvement
      in a single latent cognitive change variable was associated with subsequent
      reductions in both daycare and special accommodation costs (model 4). CONCLUSION:
      This study exemplifies a method of using cost changes to investigate the effects
      and mechanisms of CRT and suggests that executive function change may be an
      important target if we are to reduce disability and resultant health and social
      care costs.

PMID- 24682213
TI  - Filamentous supramolecular peptide-drug conjugates as highly efficient drug
      delivery vehicles.
AB  - We report here a facile approach to prepare filamentous supramolecular peptide
      drug conjugates with precise drug/carrier stoichiometry, nearly 100% loading
      efficiency and exceptional anti-cancer drug efficacy for chemotherapy. 

PMID- 24682214
TI  - Ion mobility spectrometry in breath research.
AB  - The number of publications in the field of breath analysis using different types
      of ion mobility spectrometers (IMS) has increased over the last few years. In
      this paper, the publications between 2010 and 2013 are reviewed with respect to
      different types of IMS such as differential mobility spectrometers, high-field
      asymmetric waveform ion mobility spectrometers and multi-capillary columns
      coupled to conventional IMS. The analytes detected by IMS and declared with
      significance to a specific medical question were considered further with respect
      to medical and analytical questions. In total, 42 different analytes were found
      to be detected using IMS on a high significance level and were compared to
      findings using other analytical methods with respect to the individual analyte. 

PMID- 24682217
TI  - Cancer mortality by country of birth, sex, and socioeconomic position in Sweden,
      1961-2009.
AB  - In 2010, cancer deaths accounted for more than 15% of all deaths worldwide, and
      this fraction is estimated to rise in the coming years. Increased cancer
      mortality has been observed in immigrant populations, but a comprehensive
      analysis by country of birth has not been conducted. We followed all individuals
      living in Sweden between 1961 and 2009 (7,109,327 men and 6,958,714 women), and
      calculated crude cancer mortality rates and age-standardized rates (ASRs) using
      the world population for standardization. We observed a downward trend in all
      site ASRs over the past two decades in men regardless of country of birth but no
      such trend was found in women. All-site cancer mortality increased with
      decreasing levels of education regardless of sex and country of birth (p for
      trend <0.001). We also compared cancer mortality rates among foreign-born (13.9%)
      and Sweden-born (86.1%) individuals and determined the effect of education level
      and sex estimated by mortality rate ratios (MRRs) using multivariable Poisson
      regression. All-site cancer mortality was slightly higher among foreign-born than
      Sweden-born men (MRR = 1.05, 95% confidence interval 1.04-1.07), but similar
      mortality risks was found among foreign-born and Sweden-born women. Men born in
      Angola, Laos, and Cambodia had the highest cancer mortality risk. Women born in
      all countries except Iceland, Denmark, and Mexico had a similar or smaller risk
      than women born in Sweden. Cancer-specific mortality analysis showed an increased
      risk for cervical and lung cancer in both sexes but a decreased risk for colon,
      breast, and prostate cancer mortality among foreign-born compared with Sweden
      born individuals. Further studies are required to fully understand the causes of
      the observed inequalities in mortality across levels of education and countries
      of birth. 

PMID- 24682218
TI  - Role of the siderophore transporter SirABC in the Staphylococcus aureus
      resistance to oxidative stress.
AB  - In Staphylococcus aureus, the intracellular siderophore staphyloferrin B, which
      has been shown to chelate iron-bound to serum transferrin, is transported into
      cells by the SirABC system. In this work, we have analysed the role of the Sir
      transporter under stress conditions that resemble those imposed by the mammalian
      innate immune system. We show that exposure of S. aureus to oxidative and
      nitrosative stress generated by hydrogen peroxide and S-nitrosoglutathione,
      respectively, induced the expression of the sirA gene. The disruption of the sir
      operon led to a strain with lower viability and decreased resistance to oxidative
      stress. S. aureus sir null mutant was also analysed during infection of murine
      macrophages and shown to contribute to S. aureus survival inside macrophages.
      Altogether, our results indicate that the Sir transport system confers protection
      against reactive oxygen species, therefore, contributing to the virulence of S.
      aureus. 

PMID- 24682219
TI  - Endothelial secreted factors suppress mitogen deprivation-induced autophagy and
      apoptosis in glioblastoma stem-like cells.
AB  - Rapidly growing and highly vascularized tumors, such as glioblastoma multiforme,
      contain heterogeneous areas within the tumor mass, some of which are
      inefficiently supplied with nutrients and oxygen. While the cell death rate is
      elevated in such zones, tumor cells are still suspected to grow and survive
      independently of extracellular growth factors. In line with this, glioblastoma
      stem-like cells (GSCs) are found closely associated with brain vasculature in
      situ, and as such are most likely in a protected microenvironment. However, the
      behavior of GSCs under deprived conditions has not been explored in detail. Using
      a panel of 14 patient-derived GSCs, we report that ex vivo mitogen deprivation
      impaired self-renewal capability, abolished constitutive activation of the mTor
      pathway, and impinged on GSC survival via the engagement of autophagic and
      apoptotic cascades. Moreover, pharmacological inhibition of the mTor pathway
      recapitulated the mitogen deprivation scenario. In contrast, blocking either
      apoptosis or autophagy, or culturing GSCs with endothelial-secreted factors
      partly restored mTor pathway activation and rescued GSC survival. Overall, our
      data suggest that GSCs are addicted to mTor, as their survival and self-renewal
      are profoundly dependent on this signaling axis. Thus, as mTor governs the fate
      of GSCs under both deprivation conditions and in the presence of endothelial
      factors, it could be a key target for therapeutic purposes. 

PMID- 24682220
TI  - Caffeine inhibits the activation of hepatic stellate cells induced by
      acetaldehyde via adenosine A2A receptor mediated by the cAMP/PKA/SRC/ERK1/2/P38
      MAPK signal pathway.
AB  - Hepatic stellate cell (HSC) activation is an essential event during alcoholic
      liver fibrosis. Evidence suggests that adenosine aggravates liver fibrosis via
      the adenosine A2A receptor (A2AR). Caffeine, which is being widely consumed
      during daily life, inhibits the action of adenosine. In this study, we attempted
      to validate the hypothesis that caffeine influences acetaldehyde-induced HSC
      activation by acting on A2AR. Acetaldehyde at 50, 100, 200, and 400 MUM
      significantly increased HSC-T6 cells proliferation, and cell proliferation
      reached a maximum at 48 h after exposure to 200 MUM acetaldehyde. Caffeine and
      the A2AR antagonist ZM241385 decreased the cell viability and inhibited the
      expression of procollagen type I and type III in acetaldehyde-induced HSC-T6
      cells. In addition, the inhibitory effect of caffeine on the expression of
      procollagen type I was regulated by A2AR-mediated signal pathway involving cAMP,
      PKA, SRC, and ERK1/2. Interestingly, caffeine's inhibitory effect on the
      expression of procollagen type III may depend upon the A2AR-mediated P38 MAPK
      dependent pathway. CONCLUSIONS: Caffeine significantly inhibited acetaldehyde
      induced HSC-T6 cells activation by distinct A2AR mediated signal pathway via
      inhibition of cAMP-PKA-SRC-ERK1/2 for procollagen type I and via P38 MAPK for
      procollagen type III.

PMID- 24682221
TI  - Potential regulatory role of microRNAs in the development of bovine
      gastrointestinal tract during early life.
AB  - This study aimed to investigate the potential regulatory role of miRNAs in the
      development of gastrointestinal tract (GIT) during the early life of dairy
      calves. Rumen and small intestinal (mid-jejunum and ileum) tissue samples were
      collected from newborn (30 min after birth; n = 3), 7-day-old (n = 6), 21-day-old
      (n = 6), and 42-day-old (n = 6) dairy calves. The miRNA profiling was performed
      using Illumina RNA-sequencing and the temporal and regional differentially
      expressed miRNAs were further validated using qRT-PCR. Analysis of 16S rRNA gene
      copy numbers was used to quantify total bacteria, Bifidobacterium and
      Lactobacillus species. The expression of miR-143 was abundant in all three gut
      regions, at all time points and it targets genes involved primarily in the
      proliferation of connective tissue cells and muscle cells, suggesting a role in
      regulating rapid tissue development during the early life of calves. The
      expression of miR-146, miR-191, miR-33, miR-7, miR-99/100, miR-486, miR-145, miR
      196 and miR-211 displayed significant temporal differences (FDR <0.05), while miR
      192/215, miR-194, miR-196, miR-205 and miR-31 revealed significant regional
      differences (FDR <0.05). The expression levels of miR-15/16, miR-29 and miR-196
      were positively correlated with the copy numbers of 16S rRNA gene of
      Bifidobacterium or Lactobacillus species or both (P<0.05). Functional analysis
      using Ingenuity Pathway Analysis identified the above mentioned differentially
      expressed miRNAs as potential regulators of gut tissue cell proliferation and
      differentiation. The bacterial density-associated miRNAs were identified as
      modulators of the development of lymphoid tissues (miR-196), maturation of
      dendritic cells (miR-29) and development of immune cells (miR-15/16). The present
      study revealed temporal and regional changes in miRNA expression and a
      correlation between miRNA expression and microbial population in the GIT during
      the early life, which provides further evidence for another mechanism by which
      host-microbial interactions play a role in regulating gut development. 

PMID- 24682222
TI  - The new cholesterol and blood pressure guidelines: perspective on the path
      forward.

PMID- 24682225
TI  - Quantum entanglement in carbon-carbon, carbon-phosphorus and silicon-silicon
      bonds.
AB  - The chemical bond is an important local concept to understand chemical compounds
      and processes. Unfortunately, like most local concepts, the chemical bond and the
      bond order do not correspond to any physical observable and thus cannot be
      determined as an expectation value of a quantum chemical operator. We recently
      demonstrated [Boguslawski et al., J. Chem. Theory Comput., 2013, 9, 2959-2973]
      that one- and two-orbital-based entanglement measures can be applied to interpret
      electronic wave functions in terms of orbital correlation. Orbital entanglement
      emerged as a powerful tool to provide a qualitative understanding of bond-forming
      and bond-breaking processes, and allowed for an estimation of bond orders of
      simple diatomic molecules beyond the classical bonding models. In this article we
      demonstrate that the orbital entanglement analysis can be extended to polyatomic
      molecules to understand chemical bonding. 

PMID- 24682223
TI  - Renal denervation: effects on atrial electrophysiology and arrhythmias.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia and is
      associated with significant morbidity and mortality. Currently, atrial
      endocardial catheter ablation, mainly targeting focal discharges in the pulmonary
      veins, is the most widely used interventional treatment of drug-refractory AF.
      Despite technical improvements, results are not yet optimal. There is ongoing
      search for alternative and/or complementary interventional targets. Conditions
      associated with increased sympathetic activation such as hypertension, heart
      failure and sleep apnea lead to structural, neural and electrophysiological
      changes in the atrium thereby contributing to the progression from paroxysmal to
      persistent AF and increasing recurrence rate of AF after PVI. Until now,
      interventional modulation of autonomic nervous system was limited by highly
      invasive techniques. Catheter-based renal denervation (RDN) was introduced as a
      minimally invasive approach to reduce renal and whole body sympathetic activation
      with accompanying blood pressure control and left-ventricular morphological and
      functional changes in resistant hypertension. This review focuses on the
      potential atrial antiarrhythmic and antiremodeling effects of RDN in AF patients
      with hypertension, heart failure, and sleep apnea and discusses the possible role
      of RDN in the treatment of AF.

PMID- 24682226
TI  - A portable system for identifying urinary tract infection in primary care using a
      PC-based chromatic technique.
AB  - An approach is described for monitoring urine samples using a portable system
      based on chromatic techniques and for predicting urinary tract infection (UTI)
      from the results. The system uses a webcam-computer combination with the screen
      of a computer visual display unit as a tuneable illumination source. It is shown
      that the system can operate in a robust manner under ambient lighting conditions
      and with potential for use as a point of care test in primary care. The present
      approach combines information on urine liquid concentration and turbidity. Its
      performance in an exploratory study is compared with microbiological culture of
      200 urine samples, of which 79 had bacterial growth >10(5) colony forming
      unit/millilitre (cfu ml(-1)) indicative of UTI. It is shown that both sensitivity
      and negative predictive value of 0.92 could be achieved. 

PMID- 24682224
TI  - Association of variants in DRD2 and GRM3 with motor and cognitive function in
      first-episode psychosis.
AB  - Similar smooth pursuit eye tracking dysfunctions are present across psychotic
      disorders. They include pursuit initiation and maintenance deficits that
      implicate different functional brain systems. This candidate gene study examined
      psychosis-related genotypes regulating dopamine and glutamate neurotransmission
      in relation to these pursuit deficits. One hundred and thirty-eight untreated
      first-episode patients with a psychotic disorder were genotyped for four markers
      in DRD2 and four markers in GRM3. The magnitude of eye movement abnormality in
      patients was defined in relation to performance of matched healthy controls (N =
      130). Eighty three patients were followed after 6 weeks of antipsychotic
      treatment. At baseline, patients with a -141C deletion in DRD2 rs1799732 had
      slower initiation eye velocity and longer pursuit latency than CC insertion
      carriers. Further, GRM3 rs274622_CC carriers had poorer pursuit maintenance than
      T-carriers. Antipsychotic treatment resulted in prolonged pursuit latency in DRD2
      rs1799732_CC insertion carriers and a decline in pursuit maintenance in GRM3
      rs6465084_GG carriers. The present study demonstrates for the first time that
      neurophysiological measures of motor and neurocognitive deficits in patients with
      psychotic disorders have different associations with genes regulating dopamine
      and glutamate systems, respectively. Alterations in striatal D2 receptor activity
      through the -141C Ins/Del polymorphism could contribute to pursuit initiation
      deficits in psychotic disorders. Alterations in GRM3 coding for the mGluR3
      protein may impair pursuit maintenance by compromising higher perceptual and
      cognitive processes that depend on optimal glutamate signaling in corticocortical
      circuits. DRD2 and GRM3 genotypes also selectively modulated the severity of
      adverse motor and neurocognitive changes resulting from antipsychotic treatment.

PMID- 24682229
TI  - 11th Dresdner Sensor Symposium--a conference on sensors, measurement techniques,
      and medical engineering.

PMID- 24682230
TI  - Sol-gel approach for fabrication of coated anodized titanium wire for solid-phase
      microextraction: highly efficient adsorbents for enrichment of trace polar
      analytes.
AB  - Nanotubular titania film was prepared in situ on titanium wire and was used as
      the fiber substrate for solid-phase microextraction (SPME) because of its high
      surface-to-volume ratio, easy preparation, and mechanical stability. Three
      different functional coatings, beta-cyclodextrin (beta-CD), beta-cyclodextrin-co
      poly(ethylenepropylene glycol) (beta-CD/PEG), and polyethylene glycol (PEG)-based
      sorbents were chemically bonded to the nanostructured wire surface via sol-gel
      technology to further enhance the absorbing capability and extraction
      selectivity. Coupled to gas chromatography-flame ionic detection (GC-FID), the
      prepared SPME fibers were investigated using diverse compounds. The results
      indicated that the fibers showed good mechanical strength, excellent thermal
      stability, and wonderful capacity and selectivity to polar compounds, including
      polar aromatic compounds, alcohols, and ketones. Combining the superior
      hydrophilic property of a bonded functional molecule and the highly porous
      structure of a fiber coating, the prepared PEG-coated SPME fiber showed much
      higher adsorption affinity to ephedrine and methylephedrine than beta-CD and beta
      CD/PEG fibers. The as-established PEG-coated SPME-GC analytical method provided
      excellent sensitivity (LODs, 0.004 and 0.001 ng mL(-1) for ephedrine and
      methylephedrine, respectively) and better linear range (0.01-2 000 MUg L(-1)). In
      addition, it has surprising repeatability and reproducibility. Finally, the
      present approach was used to analyze ephedrine and methylephedrine from real
      urine samples, and reliable results were obtained.

PMID- 24682227
TI  - Dual role of acetaminophen in promoting hepatoma cell apoptosis and kidney
      fibroblast proliferation.
AB  - Acetaminophen (APAP), is a safe analgesic and antipyretic drug at therapeutic
      dose, and is widely used in the clinic. However, high doses of APAP can induce
      hepatotoxicity and nephrotoxicity. Most studies have focused on high-dose APAP
      induced acute liver and kidney injury. So far, few studies have investigated the
      effects of the therapeutic dose (1/10 of the high dose) or of the low dose (1/100
      of the high dose) of APAP on the cells. The aim of this study was to investigate
      the cellular effects of therapeutic- or low-dose APAP treatment on hepatoma cells
      and kidney fibroblasts. As expected, high-dose APAP treatment inhibited while
      therapeutic and low-dose treatment did not inhibit cell survival of kidney
      tubular epithelial cells. In addition, therapeutic-dose treatment induced an
      increase in the H2O2 level, activated the caspase-9/-3 cascade, and induced cell
      apoptosis of hepatoma cells. Notably, APAP promoted fibroblast proliferation,
      even at low doses. This study demonstrates that different cellular effects are
      exerted upon treatment with different APAP concentrations. Our results indicate
      that treatment with the therapeutic dose of APAP may exert an antitumor activity
      on hepatoma, while low-dose treatment may be harmful for patients with fibrosis,
      since it may cause proliferation of fibroblasts. 

PMID- 24682231
TI  - Trace analysis of benzophenone-derived compounds in surface waters and sediments
      using solid-phase extraction and microwave-assisted extraction followed by gas
      chromatography-mass spectrometry.
AB  - This study describes a procedure for determining eight benzophenone-derived
      compounds in surface waters and sediments. These include the pharmaceutical
      ketoprofen, its phototransformation products 3-ethylbenzophenone and 3
      acetylbenzophenone, and five benzophenone-type ultraviolet (UV) filters. The
      proposed analytical method involves the pre-concentration of water samples by
      solid-phase extraction (SPE) and microwave-assisted extraction (MAE) of sediment
      samples followed by derivatization and analysis by gas chromatography-mass
      spectrometry. Different parameters were investigated to achieve optimal method
      performance. Recoveries of 91 to 96 % from water samples were obtained using HLB
      Oasis SPE cartridges, whereas MAE of sediments (30 min at 150  degrees C) gave
      recoveries of 80 to 99 %. Limits of detection were between 0.1 and 1.9 ng L(-1)
      for water samples and from 0.1 to 1.4 ng g(-1) for sediment samples. The
      developed method was applied to environmental samples and revealed the presence
      of UV filters in the majority of the surface waters with up to 690 ng L(-1) of 2
      hydroxy-4-methoxybenzophenone. By contrast, ketoprofen (<=2,900 ng L(-1)) and its
      degradation products (<=320 ng L(-1)) were found in only two rivers, both
      receiving wastewater treatment plant effluents. Sediment analysis revealed
      benzophenone to be present in concentrations up to 650 ng g(-1), whereas
      concentrations of other compounds were considerably lower (<=32 ng L(-1)). For
      the first time, quantifiable amounts of two ketoprofen transformation products in
      the aqueous environment are reported.

PMID- 24682232
TI  - A chemometric approach to characterization of ionic liquids for gas
      chromatography.
AB  - A chemometric study was carried out to characterize three ionic liquid types
      (ILs) with hexacationic imidazolium, polymeric imidazolium, and phosphonium
      cationic cores, using a range of contra-anions such as halogens, thiocyanate,
      boron anions, triflate, and bistriflimide. The solvation parameter model
      developed by Abraham et al., unsupervised techniques as cluster analysis (CA),
      and supervised techniques as linear discriminant analysis (LDA), step-LDA,
      quadratic discriminant analysis (QDA), and multivariate regression techniques as
      discriminant partial least squares (D-PLS), or multiple linear regression (MLR)
      were used to characterize the functionalized ILs above. CA established two main
      groups of phases, those with an acidic H-bond and those with basic ones. Once
      detected, the two natural groups, a linear and quadratic delimiters with good
      classification (>96 %) and prediction (>92 %) capacities were computed. The use
      of step-LDA technique allowed us to establish that a, b, and s solvation
      parameters were the most discriminant variables. These variables were used for
      modeling purposes, and a D-PLS and MLR models were constructed using a binary
      response. The explained variance of categorical variable by the model validated
      by cross-validation was 65 %, and 94.5 % of ILs were correctly predicted. IL
      characterization carried out would allow the appropriate selection of phases for
      gas chromatography (GC). 

PMID- 24682233
TI  - Validation of a multi-analyte LC-MS/MS method for screening and quantification of
      87 psychoactive drugs and their metabolites in hair.
AB  - A multi-analyte method for the detection and quantification of 87 psychoactive
      drugs (antidepressants, antipsychotics, benzodiazepines, and z-drugs) in human
      hair has been developed and fully validated using the liquid chromatography
      tandem mass spectrometry system. Due to the remarkable increase in requests of
      hair sample tests (such as for driver's license renewals, child custody, DFA
      cases, and postmortem toxicology), we focused on the development of a rapid
      sample preparation. About 20 mg of hair samples, previously washed and cut into
      snippets, was ultrasonicated with 700 MUl of methanol. Samples were then directly
      analyzed using a 4000 QTRAP (AB SCIEX, Foster City, CA, USA) with an electrospray
      ionization (ESI) Turbo V(TM) Ion Source. The validation criteria parameters were
      satisfactory and in accordance with the international guidelines. All the
      compounds tested were successfully detected. One important aspect is the LODs in
      the low picogram per milligram concentration which may suggest a potential use of
      this method in cases of detection of single drug exposure. However, the LC-MS/MS
      method has been successfully applied for the analysis of postmortem cases (n =
      9). 

PMID- 24682234
TI  - Pollen sensitivity to ultraviolet-B (UV-B) suggests floral structure evolution in
      alpine plants.
AB  - Various biotic and abiotic factors are known to exert selection pressures on
      floral traits, but the influence of ultraviolet-B (UV-B) light on the evolution
      of flower structure remains relatively unexplored. We have examined the
      effectiveness of flower structure in blocking radiation and the effects of UV-B
      on pollen viability in 42 species of alpine plants in the Hengduan Mountains,
      China. Floral forms were categorized as either protecting or exposing pollen
      grains to UV-B. The floral materials of plants with exposed and protected pollen
      grains were able to block UV-B at similar levels. Exposure to UV-B radiation in
      vitro resulted in a significantly greater loss of viability in pollen from plant
      species with protective floral structures. The pronounced sensitivity of
      protected pollen to UV-B radiation was associated with the type of flower
      structure. These findings demonstrate that UV-B plays an important role in the
      evolution of protective floral forms in alpine plants. 

PMID- 24682236
TI  - Asparagus-induced fixed food eruptions mimicking cutaneous lupus.

PMID- 24682237
TI  - Expression of GAD67 and Dlx5 in the taste buds of mice genetically lacking Mash1.
AB  - It has been reported that a subset of type III taste cells express glutamate
      decarboxylase (GAD)67, which is a molecule that synthesizes gamma-aminobutyric
      acid (GABA), and that Mash1 could be a potential regulator of the development of
      GABAnergic neurons via Dlx transcription factors in the central nervous system.
      In this study, we investigated the expression of GAD67 and Dlx in the embryonic
      taste buds of the soft palate and circumvallate papilla using Mash1 knockout
      (KO)/GAD67-GFP knock-in mice. In the wild-type animal, a subset of type III taste
      cells contained GAD67 in the taste buds of the soft palate and the developing
      circumvallate papilla, whereas GAD67-expressing taste bud cells were missing from
      Mash1 KO mice. A subset of type III cells expressed mRNA for Dlx5 in the wild
      type animals, whereas Dlx5-expressing cells were not evident in the apical part
      of the circumvallate papilla and taste buds in the soft palate of Mash1 KO mice.
      Our results suggest that Mash1 is required for the expression of GAD67 and Dlx5
      in taste bud cells. 

PMID- 24682235
TI  - Effect of overexpression of beta- and gamma-actin isoforms on actin cytoskeleton
      organization and migration of human colon cancer cells.
AB  - Actins are eukaryotic proteins, which are involved in diverse cellular functions
      including muscle contraction, cell motility, adhesion and maintenance of cell
      shape. Cytoplasmic actin isoforms beta and gamma are ubiquitously expressed and
      essential for cell functioning. However, their unique contributions are not very
      well understood. The aim of this study was to determine the effect of beta- and
      gamma-actin overexpression on the migration capacity and actin cytoskeleton
      organization of human colon adenocarcinoma BE cells. In cells overexpressing beta
      or gamma-actin, distinct cytoskeletal actin rearrangements were observed under
      the laser scanning confocal microscope. Overexpressed actins localized at the
      submembranous region of the cell body, especially near to the leading edge and on
      the tips of pseudopodia. The cells transfected with plasmids containing cDNA for
      beta- or gamma-actin were characterized by increased migration and invasion
      capacities. However, the migration velocity was statistically significantly
      higher only in the case of gamma-actin overexpressing cells. In conclusion, the
      increased level of beta- or gamma-actin leads to actin cytoskeletal remodeling
      followed by an increase in migration and invasion capacities of human colon BE
      cells. These data suggest that expression of both actin isoforms has an impact on
      cancer cell motility, with the subtle predominance of gamma-actin, and may
      influence invasiveness of human colon cancer. 

PMID- 24682238
TI  - Peri-procedural povidone-iodine rectal preparation reduces microorganism counts
      and infectious complications following ultrasound-guided needle biopsy of the
      prostate.
AB  - PURPOSE: The purpose of the study was to evaluate whether a peri-procedural
      povidone-iodine rectal preparation (PIRP) prior to transrectal ultrasound-guided
      prostate needle biopsy (TRUS PNB) can reduce microorganism colony counts and
      infectious complications. METHODS: Our institutional TRUS PNB database was
      reviewed to identify infectious post-biopsy complications (defined as fever >38.5
      degrees C with positive culture). The last 570 biopsy patients were divided into
      those administered only preoperative oral and/or parenteral antibiotics (n = 456;
      chronologically cohorts A-D) versus men receiving peri-procedural PIRP in
      conjunction with standard preoperative antibiotics (n = 114; cohort E). Rectal
      cultures were obtained in the PIRP cohort to quantify changes in microorganism
      colony counts. RESULTS: Mean baseline PSA for patients was 11.6 ng/ml, 63 % were
      undergoing an initial biopsy, and 17 % had documented use of antibiotic therapy
      within the previous 6 months. A reduction in infectious complications was
      observed when comparing the conventional antibiotic (cohorts A-D) versus PIRP
      (cohort E) group (1.8 vs. 0 %), with the largest magnitude of decline occurring
      in the concurrent contemporary cohorts (cohort D-5.3 % vs. cohort E-0 %, p =
      0.03). Rectal cultures obtained in 92 men before and after PIRP administration
      noted a 97 % reduction in microorganism colonies (2.1 * 10(5) vs. 6.3 * 10(3)
      CFU/ml, p < 0.001). No adverse reactions to the PIRP were reported by patients 7
      days post-biopsy. CONCLUSIONS: Peri-procedural PIRP decreased microorganism
      colony counts and effectively reduced infectious complications following TRUS
      PNB. This safe, cheap, and simple strategy may be a reasonable alternative to
      systemic or targeted antibiotic therapy to reduce post-biopsy infections.

PMID- 24682240
TI  - Agomelatine and duloxetine synergistically modulates apoptotic pathway by
      inhibiting oxidative stress triggered intracellular calcium entry in neuronal
      PC12 cells: role of TRPM2 and voltage-gated calcium channels.
AB  - Calcium ion (Ca(2+)) is one of the universal second messengers, which acts in a
      wide range of cellular processes. Results of recent studies indicated that ROS
      generated by depression leads to loss of endoplasmic reticulum-Ca(2+)
      homeostasis, oxidative stress, and apoptosis. Agomelatine and duloxetine are
      novel antidepressant and antioxidant drugs and may reduce oxidative stress,
      apoptosis, and Ca(2+) entry through TRPM2 and voltage-gated calcium channels. We
      tested the effects of agomelatine, duloxetine, and their combination on oxidative
      stress, Ca(2+) influx, mitochondrial depolarization, apoptosis, and caspase
      values in the PC-12 neuronal cells. PC-12 neuronal cells were exposed in cell
      culture and exposed to appropriate non-toxic concentrations and incubation times
      for agomelatine were determined in the neurons by assessing cell viability. Then
      PC-12 cells were incubated with agomelatine and duloxetine for 24 h. Treatment of
      cultured PC-12 cells with agomelatine, duloxetine, and their combination results
      in a protection on apoptosis, caspase-3, caspase-9, mitochondrial membrane
      depolarization, cytosolic ROS production, glutathione peroxidase, reduced
      glutathione, and lipid peroxidation, values. Ca(2+) entry through non-specific
      TRPM2 channel blocker (2-APB) and voltage-gated Ca(2+) channel blockers
      (verapamil and diltiazem) was modulated by agomelatine and duloxetine. However,
      effects of duloxetine on the Ca(2+) entry through TRPM2 channels were higher than
      in agomelatine. Results of current study suggest that the agomelatine and
      duloxetine are useful against apoptotic cell death and oxidative stress in PC-12
      cells, which seem to be dependent on mitochondrial damage and increased levels of
      intracellular Ca(2+) through activation of TRPM2 and voltage-gated Ca(2+)
      channels.

PMID- 24682239
TI  - Automated procedure for contact-map-based protein structure reconstruction.
AB  - Knowledge of the three-dimensional structures of ion channels allows for modeling
      their conductivity characteristics using biophysical models and can lead to
      discovering their cellular functionality. Recent studies show that quality of
      structure predictions can be significantly improved using protein contact site
      information. Therefore, a number of procedures for protein structure prediction
      based on their contact-map have been proposed. Their comparison is difficult due
      to different methodologies used for validation. In this work, a Contact Map-to
      Structure pipeline (C2S_pipeline) for contact-based protein structure
      reconstruction is designed and validated. The C2S_pipeline can be used to
      reconstruct monomeric and multimeric proteins. The median RMSD of structures
      obtained during validation on a representative set of protein structures, equaled
      5.27 A, and the best structure was reconstructed with RMSD of 1.59 A. The
      validation is followed by a detailed case study on the KcsA ion channel. Models
      of KcsA are reconstructed based on different portions of contact site
      information. Structural feature analysis of acquired KcsA models is supported by
      a thorough analysis of electrostatic potential distributions inside the channels.
      The study shows that electrostatic parameters are correlated with structural
      quality of models. Therefore, they can be used to discriminate between high and
      low quality structures. We show that 30 % of contact information is needed to
      obtain accurate structures of KcsA, if contacts are selected randomly. This
      number increases to 70 % in case of erroneous maps in which the remaining
      contacts or non-contacts are changed to the opposite. Furthermore, the study
      reveals that local reconstruction accuracy is correlated with the number of
      contacts in which amino acid are involved. This results in higher reconstruction
      accuracy in the structure core than peripheral regions.

PMID- 24682241
TI  - Resveratrol protects primary cortical neuron cultures from transient oxygen
      glucose deprivation by inhibiting MMP-9.
AB  - It was recently shown that resveratrol exerts neuroprotective effects against
      cerebral ischemia in mice. The aim of the present study was to further confirm
      these effects in in vitro primary cortical neuron cultures with transient oxygen
      glucose deprivation (OGD), and to investigate whether these effects are due to
      the inhibition of matrix metalloproteinase-9 (MMP-9) and of cell apoptosis.
      Neuronal primary cultures of cerebral cortex were prepared from BALB/c mice
      embryos (13-15 days). Cells from 14- to 16-day cultures were subjected to OGD for
      3 h, followed by 21 h of reoxygenation to simulate transient ischemia. Different
      doses of resveratrol were added into the culture medium during the simulation of
      transient ischemia. The effect of the extracellular signal-regulated kinase (ERK)
      inhibitor U0126 was studied by adding U0126 (5 ug/ul, 4 ul) into the culture
      medium during transient ischemia; as a control, we used treatment of cells with
      50 uM of resveratrol. Cell viability was investigated using the 3-[4,5
      dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay.
      Cell apoptosis was assessed by flow cytometry. The effects of resveratrol on the
      expression of MMP-9 were analyzed by western blotting and reverse transcription
      polymerase chain reaction (RT-PCR), while the levels of ERK, phosphorylated (p)
      ERK, cleaved caspase-3, Bax and Bcl-2 were measured by western blotting. The
      results of the MTT assay showed that cell viability is significantly reduced by
      transient OGD. OGD induced cell apoptosis, the expression of Bax and the
      activation of caspase-3 and ERK, inhibited the expression of Bcl-2 and increased
      the expression of MMP-9, while these effects were reversed by treatment with
      resveratrol. The therapeutic efficacy of resveratrol was shown to be dose
      dependent, with the most suitable dose range determined at 50-100 uM. Treatment
      with U0126 inhibited MMP-9 and Bax expression and caspase-3 activation, while it
      further promoted the expression of the anti-apoptotic molecule Bcl-2, suggesting
      that resveratrol inhibits MMP-9 expression and cell apoptosis by attenuating the
      activation of ERK1/2. In conclusion, OGD can induce apoptosis through canonical
      apoptotic signals and by regulating the expression of MMP-9; the anti-apoptotic
      activity of resveratrol and its inhibitory effect on MMP-9 expression contribute
      in the reduced activation of ERK.

PMID- 24682242
TI  - Proportion of US adults potentially affected by the 2014 hypertension guideline.
AB  - IMPORTANCE: The new 2014 blood pressure (BP) guideline released by the panel
      members appointed to the Eighth Joint National Committee (JNC 8; 2014 BP
      guideline) proposed less restrictive BP targets for adults aged 60 years or older
      and for those with diabetes and chronic kidney disease. OBJECTIVE: To estimate
      the proportion of US adults potentially affected by recent changes in
      recommendations for management of hypertension. DESIGN: Cross-sectional,
      nationally representative survey. PARTICIPANTS: Using data from the National
      Health and Nutrition Examination Survey between 2005 and 2010 (n = 16,372), we
      evaluated hypertension control and treatment recommendations for US adults. MAIN
      OUTCOMES AND MEASURES: Proportion of adults estimated to meet guideline-based BP
      targets under the 2014 BP guideline and under the previous seventh Joint National
      Committee on Prevention, Detection, Evaluation, and Treatment of High Blood
      Pressure (JNC 7) guideline. RESULTS: The proportion of younger adults (18-59
      years) with treatment-eligible hypertension under the JNC 7 guideline was 20.3%
      (95% CI, 19.1%-21.4%) and decreased to 19.2% (95% CI, 18.1%-20.4%) under the 2014
      BP guideline. Larger declines were observed among older adults (>=60 years),
      decreasing from 68.9% (95% CI, 66.9%-70.8%) under JNC 7 to 61.2% (95% CI, 59.3%
      63.0%) under the 2014 BP guideline. The proportion of adults with treatment
      eligible hypertension who met BP goals increased slightly for younger adults,
      from 41.2% (95% CI, 38.1%-44.3%) under JNC 7 to 47.5% (95% CI, 44.4%-50.6%) under
      the 2014 BP guideline, and more substantially for older adults, from 40.0% (95%
      CI, 37.8%-42.3%) under JNC 7 to 65.8% (95% CI, 63.7%-67.9%) under the 2014 BP
      guideline. Overall, 1.6% (95% CI, 1.3%-1.9%) of US adults aged 18-59 years and
      27.6% (95% CI, 25.9%-29.3%) of adults aged 60 years or older were receiving BP
      lowering medication and meeting more stringent JNC 7 targets. These patients may
      be eligible for less stringent or no BP therapy with the 2014 BP guideline.
      CONCLUSIONS AND RELEVANCE: Compared with the JNC 7 guideline, the 2014 BP
      guideline from the panel members appointed to the JNC 8 was associated with a
      reduction in the proportion of US adults recommended for hypertension treatment
      and a substantial increase in the proportion of adults considered to have
      achieved goal BP, primarily in older adults.

PMID- 24682243
TI  - Formation of interconnected morphologies via nanorod inclusion in the confined
      assembly of symmetric block copolymers.
AB  - We have investigated the effect of nanorods on the symmetry breaking of a model
      diblock copolymer under cylindrical confinement using coarse-grained molecular
      dynamics. Unlike nanoparticles, nanorods can readily be interconnected with each
      other and also induce connection across self-assembly domains at much lower
      loading than nanoparticles. Such interconnecting nanorods, when incorporated
      within the nanofiber confined assembled block copolymer, have great potential for
      providing highly conductive pathways for energy applications, such as battery
      electrodes and separators. Symmetric block copolymers (BCP) under cylindrical
      confinement with a nanorod aspect ratio (N) of 1, 5, and 10 are examined with
      three different types of nanorod-BCP attractions: (a) neutral nanorods, (b) A
      (wall-attractive phase)-attractive nanorods, and (c) B (wall-repulsive phase)
      attractive nanorods. The system was studied with both selective and neutral
      walls, which affect the orientation of the interconnected nanorod network. Upon
      close examination of the BCP-nanorod self-assembly, we discovered that the ratio
      of the interphase distance to the nanorod aspect ratio (I/N) can be correlated to
      the onset of nanorod interconnectivity and formation of asymmetrical
      interconnected BCP morphology. By developing a phase diagram with respect to I/N,
      one can predict the formation of desired BCP morphology and the critical loading
      of nanorods for connected morphologies in cylindrical confinement. 

PMID- 24682244
TI  - Suicidality in the prospective Zurich study: prevalence, risk factors and gender.
AB  - Our prospective Zurich study (1978-2008) found that suicidal ideation had
      occurred in 40.5% and suicide attempts in 6.6% of the population by age 50.
      Important gender differences were found in both suicidality and its risk factors.
      Suicide attempts were earlier and more frequent among women than among men: 70
      versus 44% reported their first suicide attempt before 20. For women, the
      relative risk of suicide attempts was 1.6, but the relative risk of suicidal
      ideation was about equal (1.1 for women). The main risk factors for suicidal
      ideation in women were low social support (OR 4.0) and frequent punishment in
      childhood (OR 3.7), and in men, a depressive (OR 6.5) and an anxious personality
      (OR 4.6). The main risk factors for suicide attempts in women were a broken home
      (OR 10.2) and sexual abuse/violence (OR 7.9) in childhood; in men, no
      multivariate analyses of suicide attempt were conducted because of insufficient
      statistical power.

PMID- 24682245
TI  - Memory impedance in TiO2 based metal-insulator-metal devices.
AB  - Large attention has recently been given to a novel technology named memristor,
      for having the potential of becoming the new electronic device standard. Yet, its
      manifestation as the fourth missing element is rather controversial among
      scientists. Here we demonstrate that TiO2-based metal-insulator-metal devices are
      more than just a memory-resistor. They possess resistive, capacitive and
      inductive components that can concurrently be programmed; essentially exhibiting
      a convolution of memristive, memcapacitive and meminductive effects. We show how
      non-zero crossing current-voltage hysteresis loops can appear and we
      experimentally demonstrate their frequency response as memcapacitive and
      meminductive effects become dominant. 

PMID- 24682246
TI  - Impaired cortical oscillatory coupling in mild cognitive impairment: anatomical
      substrate and ApoE4 effects.
AB  - Our current knowledge about the anatomical substrate of impaired resting-state
      cortical oscillatory coupling in mild cognitive impairment is still rudimentary.
      Here, we show that both resting-state oscillatory coupling and its anatomical
      correlates clearly distinguish healthy older (HO) adults from individuals with
      amnestic mild cognitive impairment (aMCI). aMCI showed failures in neural-phase
      coupling of resting-state electroencephalographic alpha activity mostly evident
      between fronto-temporal and parietal regions. As oligomers of amyloid-beta
      (Abeta) are linked to synaptic dysfunction in Alzheimer's disease (AD), we
      further investigated whether plasma concentrations of these oligomers (Abeta40
      and Abeta42) accounted for impaired patterns of oscillatory coupling in aMCI.
      Results revealed that decreased plasma Abeta42 was associated with augmented
      coupling of parieto-temporal regions in HO subjects, but no relationship was
      found in aMCI. Oscillatory coupling of frontal regions was also significantly
      reduced in aMCI carriers of the epsilon4 allele of the Apolipoprotein E (ApoE)
      compared to epsilon4 noncarriers, although neither neuroanatomical nor plasma
      Abeta changes accounted for this difference. However, the abnormal pattern of
      oscillatory coupling in aMCI was negatively related to volume of the angular
      gyrus, and positively related to volume of the precuneus and the splenium of the
      corpus callosum. Previous evidence suggests that all these regions are
      neuropathological targets of AD. The current study takes that scenario one step
      further, suggesting that this anatomical damage could be responsible for
      disrupted cortical oscillatory coupling in aMCI. Together, these data shed light
      on how the MCI status modifies anatomo-functional relationships underlying
      coordination of large-scale cortical systems in the resting-state. 

PMID- 24682249
TI  - Effect of bosentan therapy on ventricular and atrial function in adults with
      Eisenmenger syndrome. A prospective, multicenter study using conventional and
      Speckle tracking echocardiography.
AB  - BACKGROUND: The effect of bosentan on the ventricular and atrial performance in
      patients with Eisenmenger syndrome is unclear. In adult patients with Eisenmenger
      syndrome, we aimed to evaluate the midterm effect of bosentan on physical
      exercise, ventricular and atrial function, and pulmonary hemodynamics. METHODS:
      Forty adult patients before and after 24 weeks bosentan therapy underwent 6 min
      walk test, two-dimensional speckle tracking echocardiography, plasma NT-proBNP
      measurement and cardiac catheterization. RESULTS: After 24 weeks, bosentan
      therapy an improvement was observed regarding the 6 min walk distance from a
      median (quartile 1-quartile 3) of 382.5 (312-430) to 450 (390-510) m (p =
      0.0001), NT-proBNP from 527.5 (201-1,691.25) to 369 (179-1,246) pg/ml (p =
      0.021), right ventricular mean longitudinal systolic strain from 18 (13-22) to 19
      (14.5-25) % (p = 0.004), left ventricular mean longitudinal systolic strain from
      16 (12-21) to 17 (16-22) % (p = 0.001), right atrial mean peak longitudinal
      strain from 26 (18-34) to 28 (22-34) % (p = 0.01) and right atrial mean peak
      contraction strain from 11 (8-16) to 13 (11-16) % (p = 0.005). The invasively
      obtained Qp:Qs and Rp:Rs did not significantly change under bosentan therapy.
      CONCLUSIONS: In adult patients with Eisenmenger syndrome, bosentan therapy
      improves ventricular and atrial functions resulting in enhancement of physical
      exercise and reduction in the NT-proBNP level, while the pulmonary vascular
      resistance does not change substantially.

PMID- 24682248
TI  - Turning the tide: national policy approaches to increasing physical activity in
      seven European countries.
AB  - BACKGROUND: Physical inactivity is one of the four leading behavioural risk
      factors for non-communicable disease (NCD). Like tobacco control, increasing
      levels of health-enhancing physical activity (HEPA) will require a national
      policy framework providing direction and a clear set of actions. Despite frequent
      calls, there has been insufficient progress on policy development in the majority
      of countries around the world. This study sought and summarised national HEPA
      policy in seven European countries (Finland, Italy, the Netherlands, Norway,
      Portugal, Slovenia and Switzerland). METHODS: Data collection used a policy audit
      tool (PAT), a 27-item instrument structured into four sections. RESULTS: All
      countries reported some legislation or policy across the sectors of education,
      sport and health. Only some countries reported supportive policy in the transport
      and environment sectors. Five countries reported a stand-alone HEPA policy and
      six countries reported national recommendations. HEPA prevalence targets varied
      in magnitude and specificity and the presence of other relevant goals from
      different sectors highlighted the opportunity for joint action. Evaluation and
      the use of scientific evidence were endorsed but described as weak in practice.
      Only two countries reported a national multisector coordinating committee and
      most countries reported challenges with partnerships on different levels of
      policy implementation. CONCLUSIONS: Bringing together the key components for
      success within a national HEPA policy framework is not simple. This in-depth
      policy audit and country comparison highlighted similarities and differences and
      revealed new opportunities for consideration by other countries. These examples
      can inform countries within and beyond Europe and guide the development of
      national HEPA policy within the NCD prevention agenda.

PMID- 24682251
TI  - [Phonological development in children with cochlear implant(s)].
AB  - BACKGROUND: Normal-hearing children show signs of various phonological processes
      during language development. These processes represent simplifications of
      articulation, which are overcome at different time points. For the German
      language, there are currently no reliable data regarding whether these
      developmental stages also apply to deaf children with cochlear implants (CI).
      MATERIALS AND METHODS: Phonological development in deaf children with CI was
      examined and evaluated with the PLAKSS ("Psycholinguistischen Analyse kindlicher
      Sprechstorungen"). The results of this analysis (time of test 1 = T1, n = 33)
      were compared to those of a PLAKSS diagnostic evaluation performed 1 year
      previously (time of test 0 = T0, n = 31). RESULTS: At T1, 76 % of the whole group
      showed a phonological development that did not correspond to their hearing age
      (as measured from the time of the first CI implantation). The most frequently
      observed phonological processes were the reduction of consonant clusters and
      fronting. However, 83 % of the group had fewer phonological processes
      inappropriate to their hearing age at T1 than they did at T0. CONCLUSION: The
      phonological development of children with CI is not equivalent to their hearing
      age and is structured differently to that of normal-hearing children.

PMID- 24682252
TI  - Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk
      equations.
AB  - IMPORTANCE: The American College of Cardiology/American Heart Association
      (ACC/AHA) Pooled Cohort risk equations were developed to estimate atherosclerotic
      cardiovascular disease (CVD) risk and guide statin initiation. OBJECTIVE: To
      assess calibration and discrimination of the Pooled Cohort risk equations in a
      contemporary US population. DESIGN, SETTING, AND PARTICIPANTS: Adults aged 45 to
      79 years enrolled in the Reasons for Geographic and Racial Differences in Stroke
      (REGARDS) study between January 2003 and October 2007 and followed up through
      December 2010. We studied participants for whom atherosclerotic CVD risk may
      trigger a discussion of statin initiation (those without clinical atherosclerotic
      CVD or diabetes, low-density lipoprotein cholesterol level between 70 and 189
      mg/dL, and not taking statins; n = 10,997). MAIN OUTCOMES AND MEASURES: Predicted
      risk and observed adjudicated atherosclerotic CVD incidence (nonfatal myocardial
      infarction, coronary heart disease [CHD] death, nonfatal or fatal stroke) at 5
      years because REGARDS participants have not been followed up for 10 years.
      Additional analyses, limited to Medicare beneficiaries (n = 3333), added
      atherosclerotic CVD events identified in Medicare claims data. RESULTS: There
      were 338 adjudicated events (192 CHD events, 146 strokes). The observed and
      predicted 5-year atherosclerotic CVD incidence per 1000 person-years for
      participants with a 10-year predicted atherosclerotic CVD risk of less than 5%
      was 1.9 (95% CI, 1.3-2.7) and 1.9, respectively, risk of 5% to less than 7.5% was
      4.8 (95% CI, 3.4-6.7) and 4.8, risk of 7.5% to less than 10% was 6.1 (95% CI, 4.4
      8.6) and 6.9, and risk of 10% or greater was 12.0 (95% CI, 10.6-13.6) and 15.1
      (Hosmer-Lemeshow chi2 = 19.9, P = .01). The C index was 0.72 (95% CI, 0.70-0.75).
      There were 234 atherosclerotic CVD events (120 CHD events, 114 strokes) among
      Medicare-linked participants and the observed and predicted 5-year
      atherosclerotic CVD incidence per 1000 person-years for participants with a
      predicted risk of less than 7.5% was 5.3 (95% CI, 2.8-10.1) and 4.0,
      respectively, risk of 7.5% to less than 10% was 7.9 (95% CI, 4.6-13.5) and 6.4,
      and risk of 10% or greater was 17.4 (95% CI, 15.3-19.8) and 16.4 (Hosmer-Lemeshow
      chi2 = 5.4, P = .71). The C index was 0.67 (95% CI, 0.64-0.71). CONCLUSIONS AND
      RELEVANCE: In this cohort of US adults for whom statin initiation is considered
      based on the ACC/AHA Pooled Cohort risk equations, observed and predicted 5-year
      atherosclerotic CVD risks were similar, indicating that these risk equations were
      well calibrated in the population for which they were designed to be used, and
      demonstrated moderate to good discrimination.

PMID- 24682254
TI  - A dynamic-bioenergetics model to assess depth selection and reproductive growth
      by lake trout (Salvelinus namaycush).
AB  - We coupled dynamic optimization and bioenergetics models to assess the assumption
      that lake trout (Salvelinus namaycush) depth distribution is structured by
      temperature, food availability, and predation risk to maximize reproductive mass
      by autumn spawning. Because the model uses empirical daily thermal-depth profiles
      recorded in a small boreal shield lake (lake 373 at the Experimental Lakes Area,
      northwestern Ontario) during 2 years of contrasting thermal stratification
      patterns, we also assessed how climate-mediated changes in lakes may affect the
      vertical distribution, growth, and fitness of lake trout, a cold-water top
      predator. The depths of acoustic-tagged lake trout were recorded concurrently
      with thermal-depth profiles and were compared to model output, enabling an
      assessment of model performance in relation to the observed fish behavior and
      contrasting thermal conditions. The depths and temperatures occupied by simulated
      fish most closely resembled those of the tagged fish when risk of predation was
      included in the model, indicating the model may incorporate the most important
      underlying mechanisms that determine lake trout depth. Annual differences suggest
      less use of shallow (warm), productive habitats, resulting in markedly less
      reproductive mass, during the year with the warm stratification pattern. Mass for
      reproduction may be lower in warmer conditions because of reduced reproductive
      investment, yet survival may be inadvertently higher because risky surface waters
      may be avoided more often in warmer, shallower, and metabolically costly
      conditions. At a minimum our study suggests that lake trout reproductive mass and
      fitness may be expected to change under the anticipated longer and warmer
      stratification patterns.

PMID- 24682253
TI  - Effect of the human SOD1-G93A gene on the Nrf2/ARE signaling pathway in NSC-34
      cells.
AB  - Dominant mutations in superoxide dismutase 1 (SOD1) are a frequent cause of the
      lethal neurodegenerative disease amyotrophic lateral sclerosis (ALS). The nuclear
      factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE)
      signaling pathway is the major cellular defense mechanism against oxidative
      stress, however, its role in ALS remains to be fully elucidated. Therefore, the
      present study aimed to investigate whether the human SOD1-G93A gene affected the
      Nrf2/ARE signaling pathway in an ALS cell model. The soma became round and the
      number of neurites decreased in the NSC-34 cells transfected with the hSOD1-G93A
      gene, and the neurites were shorter and oxidative stress was increased compared
      with the normal NSC-34 cells. Furthermore, the mRNA and protein expression of
      Nrf2, heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 was significantly
      decreased in the NSC-34 cells transfected with the human SOD1-G93A gene. The
      present study indicated that human SOD1-G93A damaged the Nrf2/ARE signaling
      pathway in the ALS cell model and reduced the ability of cells to protect against
      oxidative injury.

PMID- 24682255
TI  - Rejection-mediated regression of melanocytic naevi in an immunosuppressed organ
      transplant recipient.

PMID- 24682256
TI  - In memoriam Mario Savoiardo, M.D.

PMID- 24682257
TI  - Systematic review and meta-analysis of randomized controlled trials comparing
      single incision versus conventional laparoscopic appendectomy.
AB  - BACKGROUND: Single incision laparoscopic appendectomy (SILA) has been proposed as
      an alternative to conventional laparoscopic appendectomy (CLA). OBJECTIVE: The
      aim of this study was to evaluate the safety and efficacy of SILA when compared
      with CLA through a systematic review. METHODS: We performed an electronic search
      of EMBASE, PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials.
      Randomized controlled trials (RCTs) that compared SILA with CLA were included.
      RESULTS: Six RCTs met eligibility criteria, which included a total of 800
      patients, 401 in the SILA group and 399 in the CLA group. There were no
      significant differences in terms of overall complications (odds ratio [OR] 0.93;
      95% confidence interval [CI] 0.59-1.47; p = 0.77). SILA had a higher technical
      failure rate (OR 3.30; 95% CI 1.26-8.65; p = 0.01) and required a longer
      operative time (mean difference [MD] 4.67; 95% CI 1.76-7.57; p = 0.002). SILA was
      associated with better cosmetic results (standardized MD -0.4; 95% CI -0.64 to 
      0.16; p = 0.001) and earlier return to normal activity (MD -0.64; 95% CI -1.09 to
      -0.20; p = 0.005), although these advantages should be taken with caution due to
      the small number of studies reporting these two items and the short follow-up in
      the evaluation of cosmetic results. There were no significant differences in
      terms of postoperative pain or length of hospital stay between groups.
      CONCLUSIONS: SILA is comparable to CLA in selected patients, although it is
      associated with a higher technical failure rate and longer operative time.
      Further randomized trials are needed to determine if SILA really offers benefits
      over CLA.

PMID- 24682260
TI  - Niabella thaonhiensis sp. nov., isolated from the forest soil of Kyonggi
      University in Korea.
AB  - Strain NHI-24(T) was isolated from forest soil by a polycarbonate membrane
      transwell plate. It is a Gram-negative, rod-shaped, non-motile, non-spore-forming
      bacterium. Phylogenetic analysis based on 16S rRNA gene sequence data indicated
      that strain NHI-24(T) is closely related to members of the genus Niabella: N.
      drilacis E90(T) (97.7 %), N. tibetensis 15-4(T) (96.7 %), N. aurantiaca R2A15
      11(T) (96.5 %), N. hirudinis E96(T) (95.8 %), N. soli JS13-8(T) (94.7 %), N.
      ginsengisoli NBRC106414(T) (94.4 %), and N. yanshanensis CCBAU 05354(T) (94.2 %).
      Growth temperatures range widely, from 15 to 37  degrees C, with 30  degrees C as
      the optimum. Salt tolerance ranges from 0 to 2 %. The strain grows at pH 6.5
      11.0, with an optimal range of pH 7.0-9.5. Cells produce flexirubin-type
      pigments, and the predominant menaquinone is MK-7. The major fatty acids of
      strain NHI-24(T) are iso-C15:0 (36.72 %), iso-C15:1 G (20.8 %), and summed
      feature 3 (C16:1 omega7c/C16:1 omega6c; 15.2 %). DNA-DNA hybridization values
      between strain NHI-24(T) and members of the genus Niabella range from 37 to 53 %.
      Based on these results, it is proposed that strain NHI-24(T) represents a novel
      species of the genus Niabella with the name Niabella thaonhiensis (= KACC
      17215(T) = KEMB 9005-018(T) = JCM 18864(T)).

PMID- 24682259
TI  - Effect of haylage and monensin supplementation on ruminal bacterial communities
      of feedlot cattle.
AB  - The objective of this study was to investigate the ruminal bacterial communities
      as affected by monensin, haylage, and their interaction of feedlot cattle fed 60
      % dried distillers grains with solubles in a replicated 4 * 4 Latin square
      design. Pyrosequencing analysis of the V1-V3 region (about 500 bp) of 16S rRNA
      gene from the four dietary treatments (3 treatment plus one control diets)
      collectively revealed 51 genera of bacteria within 11 phyla. Firmicutes and
      Bacteroidetes were the first and the second most predominant phyla, respectively,
      irrespective of the dietary treatments. Monensin supplementation decreased the
      proportion of Gram-positive Firmicutes while increasing that of Gram-negative
      Bacteroidetes. However, the monensin supplementation did not reduce the
      proportion of all genera of Gram-positive bacteria placed within Firmicutes and
      lowered that of some genera of Gram-negative bacteria placed within
      Bacteroidetes. Haylage supplementation appeared to attenuate inhibition of
      monensin on some genera of bacteria. Factors other than monensin and haylage
      could affect ruminal bacterial communities.

PMID- 24682261
TI  - Degradation of sulphonated azo dye Red HE7B by Bacillus sp. and elucidation of
      degradative pathways.
AB  - Bacteria capable of degrading the sulfonated azo dye Red HE7B were isolated from
      textile mill effluent contaminated soil. The most efficient isolate was
      identified as Bacillus sp. Azo1 and the isolate could successfully decolorize up
      to 89% of the dye. The decolorized cultural extract analyzed by HPLC confirmed
      degradation. Enzymatic analysis showed twofold and fourfold increase in the
      activity of azoreductase and laccase enzymes, respectively, indicating
      involvement of both reductive and oxidative enzymes in biodegradation of Red
      HE7B. Degraded products which were identified by GC/MS analysis included various
      metabolites like 8-nitroso 1-naphthol, 2-diazonium naphthalene. Mono azo dye
      intermediate was initially generated from the parent molecule. This mono azo dye
      was further degraded by the organism, into additional products, depending on the
      site of cleavage of R-N=N-R molecule. Based on the degradation products
      identified, three different pathways have been proposed. The mechanism of
      degradation in two of these pathways is different from that of the previously
      reported pathway for azo dye degradation. This is the first report of a microbial
      isolate following multiple pathways for azo dye degradation. Azo dye Red HE7B was
      observed to be phytotoxic, leading to decrease in root development, shoot length
      and seedling fresh weight. However, after biotreatment the resulting degradation
      products were non-phytotoxic.

PMID- 24682262
TI  - Inhibitory effect of selenium against Penicillium expansum and its possible
      mechanisms of action.
AB  - Some organic and inorganic salts could inhibit the growth of many pathogens.
      Selenium (Se), as an essential micronutrient, was effective in improving the
      plant resistance and antioxidant capacity at a low concentration. Penicillium
      expansum is one of the most important postharvest fungal pathogens, which can
      cause blue mold rot in various fruits and vegetables. In this study, the
      inhibitory effect of Se against P. expansum was evaluated. The result showed that
      Se strongly inhibited spore germination, germ tube elongation, and mycelial
      spread of P. expansum in the culture medium. The inhibitory effect was positively
      related to the concentration of Se used. Fluorescence microscopy observation of
      P. expansum conidia stained with propidium iodide (PI) indicated that the
      membrane integrity decreased to 37 % after the conidia were treated with Se (20
      mg/l) for 9 h. With the use of an oxidant-sensitive probe 2,7-dichlorofluorescin
      (DCHF-DA), we found that Se at 15 mg/l could induce the generation of
      intracellular reactive oxygen species (ROS). Furthermore, methane dicarboxylic
      aldehyde (MDA) content, hydrogen peroxide (H2O2), and superoxide anion (O2 (-))
      production rate in P. expansum spores exposed to Se increased markedly. Compared
      with the control, the activities of superoxide dismutase (SOD) and the content of
      glutathione (GSH) were reduced, confirming that damage of Se to cellular oxygen
      eliminating system is the main reason. These results suggest that Se might serve
      as a potential alternative to synthetic fungicides for the control of the
      postharvest disease of fruit and vegetables caused by P. expansum.

PMID- 24682263
TI  - Thoc1 inhibits cell growth via induction of cell cycle arrest and apoptosis in
      lung cancer cells.
AB  - THO complex 1 (Thoc1) is a human nuclear matrix protein that binds to the
      retinoblastoma tumor suppressor retinoblastoma protein (pRb). While some studies
      suggest that Thoc1 has characteristics of a tumor suppressor protein, whether
      Thoc1 can inhibit lung cancer cell growth is not clear. In the present study, we
      observed that Thoc1 is lowly expressed in the lung cancer cell lines SPC-A1 and
      NCI-H1975. Then, we investigated the potential effects of Thoc1 on lung cancer
      cell proliferation, cell cycle and apoptosis after stable transfection of these
      lines with a Thoc1 expression vector. We found that overexpression of Thoc1 can
      inhibit cell proliferation, induce G2/M cell cycle arrest and promote apoptosis.
      Further investigation indicated that overexpression of Thoc1 is involved in the
      inhibition of cell cycle-related proteins cyclin A1 and B1 and of pro-apoptotic
      factors Bax and caspase-3. In vivo experiments showed that tumors overexpressing
      Thoc1 display a slower growth rate than the control xenografts and show reduced
      expression of the protein Ki-67, which localized on the nuclear membrane. Taken
      together, our data show that in lung cancer cells, Thoc1 inhibits cell growth
      through induction of cell cycle arrest and apoptosis. These results indicate that
      Thoc1 may be used as a novel therapeutic target for human lung cancer treatment.

PMID- 24682264
TI  - Ethanol fermentation from molasses at high temperature by thermotolerant yeast
      Kluyveromyces sp. IIPE453 and energy assessment for recovery.
AB  - High temperature ethanol fermentation from sugarcane molasses B using
      thermophilic Crabtree-positive yeast Kluyveromyces sp. IIPE453 was carried out in
      batch bioreactor system. Strain was found to have a maximum specific ethanol
      productivity of 0.688 g/g/h with 92 % theoretical ethanol yield. Aeration and
      initial sugar concentration were tuning parameters to regulate metabolic pathways
      of the strain for either cell mass or higher ethanol production during growth
      with an optimum sugar to cell ratio 33:1 requisite for fermentation. An
      assessment of ethanol recovery from fermentation broth via simulation study
      illustrated that distillation-based conventional recovery was significantly
      better in terms of energy efficiency and overall mass recovery in comparison to
      coupled solvent extraction-azeotropic distillation technique for the same. 

PMID- 24682265
TI  - Comparison of imputation variance estimators.
AB  - Appropriate imputation inference requires both an unbiased imputation estimator
      and an unbiased variance estimator. The commonly used variance estimator,
      proposed by Rubin, can be biased when the imputation and analysis models are
      misspecified and/or incompatible. Robins and Wang proposed an alternative
      approach, which allows for such misspecification and incompatibility, but it is
      considerably more complex. It is unknown whether in practice Robins and Wang's
      multiple imputation procedure is an improvement over Rubin's multiple imputation.
      We conducted a critical review of these two multiple imputation approaches, a re
      sampling method called full mechanism bootstrapping and our modified Rubin's
      multiple imputation procedure via simulations and an application to data. We
      explored four common scenarios of misspecification and incompatibility. In
      general, for a moderate sample size (n = 1000), Robins and Wang's multiple
      imputation produced the narrowest confidence intervals, with acceptable coverage.
      For a small sample size (n = 100) Rubin's multiple imputation, overall,
      outperformed the other methods. Full mechanism bootstrapping was inefficient
      relative to the other methods and required modelling of the missing data
      mechanism under the missing at random assumption. Our proposed modification
      showed an improvement over Rubin's multiple imputation in the presence of
      misspecification. Overall, Rubin's multiple imputation variance estimator can
      fail in the presence of incompatibility and/or misspecification. For unavoidable
      incompatibility and/or misspecification, Robins and Wang's multiple imputation
      could provide more robust inferences.

PMID- 24682266
TI  - Spatiotemporal hurdle models for zero-inflated count data: Exploring trends in
      emergency department visits.
AB  - Motivated by a study exploring spatiotemporal trends in emergency department use,
      we develop a class of two-part hurdle models for the analysis of zero-inflated
      areal count data. The models consist of two components-one for the probability of
      any emergency department use and one for the number of emergency department
      visits given use. Through a hierarchical structure, the models incorporate both
      patient- and region-level predictors, as well as spatially and temporally
      correlated random effects for each model component. The random effects are
      assigned multivariate conditionally autoregressive priors, which induce
      dependence between the components and provide spatial and temporal smoothing
      across adjacent spatial units and time periods, resulting in improved inferences.
      To accommodate potential overdispersion, we consider a range of parametric
      specifications for the positive counts, including truncated negative binomial and
      generalized Poisson distributions. We adopt a Bayesian inferential approach, and
      posterior computation is handled conveniently within standard Bayesian software.
      Our results indicate that the negative binomial and generalized Poisson hurdle
      models vastly outperform the Poisson hurdle model, demonstrating that
      overdispersed hurdle models provide a useful approach to analyzing zero-inflated
      spatiotemporal data.

PMID- 24682267
TI  - The genomic landscape of mantle cell lymphoma is related to the epigenetically
      determined chromatin state of normal B cells.
AB  - In this study, we define the genetic landscape of mantle cell lymphoma (MCL)
      through exome sequencing of 56 cases of MCL. We identified recurrent mutations in
      ATM, CCND1, MLL2, and TP53. We further identified a number of novel genes
      recurrently mutated in patients with MCL including RB1, WHSC1, POT1, and SMARCA4.
      We noted that MCLs have a distinct mutational profile compared with lymphomas
      from other B-cell stages. The ENCODE project has defined the chromatin structure
      of many cell types. However, a similar characterization of primary human mature B
      cells has been lacking. We defined, for the first time, the chromatin structure
      of primary human naive, germinal center, and memory B cells through chromatin
      immunoprecipitation and sequencing for H3K4me1, H3K4me3, H3Ac, H3K36me3,
      H3K27me3, and PolII. We found that somatic mutations that occur more frequently
      in either MCLs or Burkitt lymphomas were associated with open chromatin in their
      respective B cells of origin, naive B cells, and germinal center B cells. Our
      work thus elucidates the landscape of gene-coding mutations in MCL and the
      critical interplay between epigenetic alterations associated with B-cell
      differentiation and the acquisition of somatic mutations in cancer. 

PMID- 24682269
TI  - [Not Available].

PMID- 24682270
TI  - [Not Available].

PMID- 24682268
TI  - Determination of location, size, and transmurality of chronic myocardial
      infarction without exogenous contrast media by using cardiac magnetic resonance
      imaging at 3 T.
AB  - BACKGROUND: Late-gadolinium-enhanced (LGE) cardiac MRI (CMR) is a powerful method
      for characterizing myocardial infarction (MI), but the requisite gadolinium
      infusion is estimated to be contraindicated in ~20% of patients with MI because
      of end-stage chronic kidney disease. The purpose of this study is to investigate
      whether T1 CMR obtained without contrast agents at 3 T could be an alternative to
      LGE CMR for characterizing chronic MIs using a canine model of MI. METHODS AND
      RESULTS: Canines (n=29) underwent CMR at 7 days (acute MI [AMI]) and 4 months
      (chronic MI [CMI]) after MI. Infarct location, size, and transmurality measured
      by using native T1 maps and LGE images at 1.5 T and 3 T were compared. Resolution
      of edema between AMI and CMI was examined with T2 maps. T1 maps overestimated
      infarct size and transmurality relative to LGE images in AMI (P=0.016 and
      P=0.007, respectively), which was not observed in CMI (P=0.49 and P=0.81,
      respectively) at 3 T. T1 maps underestimated infarct size and transmurality
      relative to LGE images in AMI and CMI (P<0.001) at 1.5 T. Relative to the remote
      territories, T1 of the infarcted myocardium was increased in CMI and AMI
      (P<0.05), and T2 of the infarcted myocardium was increased in AMI (P<0.001) but
      not in CMI (P>0.20) at both field strengths. Histology showed extensive
      replacement fibrosis within the CMI territories. CMI detection sensitivity and
      specificity of T1 CMR at 3 T were 95% and 97%, respectively. CONCLUSIONS: Native
      T1 maps at 3 T can determine the location, size, and transmurality of CMI with
      high diagnostic accuracy. Patient studies are necessary for clinical translation.

PMID- 24682272
TI  - [Not Available].

PMID- 24682271
TI  - [Not Available].

PMID- 24682273
TI  - [Not Available].

PMID- 24682274
TI  - High magnification digital dermoscopy of basal cell carcinoma: a single-centre
      study on 400 cases.
AB  - The aim of this study was to assess the frequency of classic dermoscopic basal
      cell carcinoma (BCC) features and the sensitivity of new descriptors, such as
      light brown nests (homogeneous and structured) only visible employing a high
      magnification digital videomicroscope. A retrospective analysis of 2,024 highly
      magnified digital images referring to 400 BCCs was performed by 3 independent
      observers, who assessed 11 classic BCC descriptors and the new ones. Light brown
      nests were detected in 40.5% of BCCs. Homogeneous ones were observable in 17.8%,
      and structured nests in 32.8%. Light brown nests were visible in 14.3% of non
      pigmented lesions, whereas in the pigmented groups these were observed in 42-54%
      of the cases. We suggest that brown nests described in this study may improve
      early recognition of superficial BCCs and of non-pigmented or slightly pigmented
      ones that may lack classic dermoscopic patterns. 

PMID- 24682275
TI  - Neuromuscular choristoma of the sciatic nerve and lumbosacral plexus: an
      association with nerve-territory undergrowth in the pelvis affecting soft tissue
      and bone.
AB  - BACKGROUND: Neuromuscular choristomas (NMC) are rare congenital lesions with
      differentiated muscle found within peripheral nerves. Patients often present with
      progressive neuropathy, undergrowth of the affected limb, and limb length
      discrepancy. In the sciatic nerve (the most common location of NMC), this may
      lead to specific manifestations in the distal limb, including progressive
      neuropathy, a shortened atrophic limb and a cavus foot. We hypothesized that the
      presence of NMC of the sciatic nerve (proximal to the sciatic notch) extending to
      the lumbosacral plexus could lead to abnormalities in proximal nerve territories
      (i.e., nerve, muscle and bone) within the hemipelvis. METHODS: A retrospective
      review of all cases of sciatic nerve NMCs diagnosed at the Mayo Clinic was
      performed. RESULTS: Seven patients were identified with sciatic nerve NMCs
      extending proximal and distal to the sciatic notch. Four patients with NMCs had
      denervation of muscles within the pelvis and ipsilateral undergrowth of bone
      which resulted in three cases of hip dysplasia. To our knowledge, the finding of
      proximal nerve-territory soft tissue and bony undergrowth (including hip
      dysplasia) in patients with NMCs involving the sciatic nerve and lumbosacral
      plexus has not previously been recognized. CONCLUSION: This finding will aid in
      both the diagnosis of the disease and an understanding of associated conditions.

PMID- 24682276
TI  - Surgeon-performed intraoperative tumor localization in recurrent papillary
      thyroid carcinoma by ultrasound-guided intratumoral indigo carmine injection.
AB  - BACKGROUND: Identification and removal of small, non-palpable tumors located
      within previous surgical scar tissue is challenging and time consuming and may be
      associated with increased risk in patients with recurrent papillary thyroid
      carcinoma (PTC). The purpose of the present study was to present our surgeon
      performed technique and to evaluate the usefulness of ultrasound-guided
      intratumoral indigo carmine injection (US-III) for intraoperative tumor
      localization in patients with recurrent PTC. METHODS: Sixteen patients with
      recurrent PTC in which tumors were <1.5 cm and not palpable were enrolled in this
      prospective study from January 2012 through March 2013. RESULTS: The mean size of
      the target tumors was 0.85 cm (range 0.4-1.3 cm) on preoperative US. The average
      time required for the US-III procedure was 7.7 min (range 5-11 min). The mean
      volume of injected indigo carmine was 0.56 mL (range 0.3-1.0 mL); this injection
      expanded the tumors by a mean of 0.2 cm (23.5% increase compared with the initial
      tumor size; range 0.0-0.4 cm), increasing the mean size of the target tumors to
      1.05 cm (range 0.5-1.5 cm). In 15 (93.8%) of the 16 patients, the recurrent
      tumors were successfully removed with the aid of US-III. No complications
      occurred in any of the patients as a result of the US-III or subsequent
      surgeries. CONCLUSIONS: US-III is a safe and effective technique that can be
      performed by the surgeon for the intraoperative localization of small non
      palpable tumors within previous scar tissue in patients with recurrent PTC.

PMID- 24682277
TI  - Reducing the burden of postoperative ileus: evaluating and implementing an
      evidence-based strategy.
AB  - BACKGROUND: Postoperative ileus remains a significant clinical and economic
      burden to the health care system. Over the last decade, several advances in both
      medical and surgical therapies have been made to reduce the incidence and
      severity of postoperative ileus. Despite these advances, though, the incidence of
      ileus remains high. This narrative review focuses on interventions aimed to
      prevent and treat postoperative ileus while presenting a step-by-step process for
      implementation of an evidenced-based strategy. METHODS: A literature search was
      performed using Medline/PubMed, and articles related to postoperative ileus were
      identified. The bibliographies of all retrieved articles were reviewed to obtain
      additional articles of relevance. RESULTS: There are many factors that can
      influence gastrointestinal recovery that can be categorized as management-, drug
      , or surgery-related. While several strategies exist to improve gastrointestinal
      recovery, few have been shown to reduce length of hospital stay. These strategies
      are described here, along with a structured approach organized by preoperative,
      intraoperative, and postoperative considerations. CONCLUSIONS: Postoperative
      ileus is associated with a significant clinical and economic burden to the health
      care system. Strategies such as the development of a multidisciplinary team and
      the creation of a multimodal protocol are encouraged with continuous quality
      assurance to assess outcomes at the local level.

PMID- 24682279
TI  - Role of thyroid surgery in the obstructive sleep apnea syndrome.
AB  - OBJECTIVES: To study the impact of thyroid surgery on obstructive sleep apnea
      syndrome (OSAS) evaluated by the apnea/hypopnea index (AHI) was studied.
      Secondary objectives were to evaluate the impact on the positional component of
      OSAS and to highlight possible predictors of improvement of OSAS after
      thyroidectomy. METHODS: Twenty-eight patients with OSAS are included in this
      monocentric study: they underwent total thyroidectomy (n = 26) or left
      loboisthmectomy. Postoperative assessment involves a nocturnal control
      polysomnography as of 60 days after surgery. RESULTS: The mean age at the time of
      surgery is 61.3 years (standard deviation +/-7.3) and average body mass index is
      29.6 kg/m2 (+/-7.3). Continuous positive airway pressure (CPAP) treatment is
      introduced preoperatively in 82% of patients. The statistical analysis shows a
      significant decrease of 33% in postoperative AHI for the total population (p =
      0.001), 77% in patients under CPAP (p = 0.05), and 27% in patients without CPAP
      (p = 0.02). CPAP therapy could be released in four patients. Given the limited
      number of subjects studied, the surgery did not impact on the positional
      component of the OSAS. Statistical analysis failed to link a predictive factor to
      AHI reduction. CONCLUSIONS: We propose thyroid surgery as an alternative or as a
      complement to CPAP treatment for the patients with goitre: it allows a
      significant decrease in postoperative AHI, allowing adaptation of the CPAP
      treatment downward, or even a release in some cases. These results need to be
      confirmed on a larger series of patients in a prospective study with standardized
      criteria for polysomnography and multivariate analysis.

PMID- 24682278
TI  - Charitable platforms in global surgery: a systematic review of their
      effectiveness, cost-effectiveness, sustainability, and role training.
AB  - OBJECTIVE: This study was designed to propose a classification scheme for
      platforms of surgical delivery in low- and middle-income countries (LMICs) and to
      review the literature documenting their effectiveness, cost-effectiveness,
      sustainability, and role in training. Approximately 28 % of the global burden of
      disease is surgical. In LMICs, much of this burden is borne by a rapidly growing
      international charitable sector, in fragmented platforms ranging from short-term
      trips to specialized hospitals. Systematic reviews of these platforms, across
      regions and across disease conditions, have not been performed. METHODS: A
      systematic review of MEDLINE and EMBASE databases was performed from 1960 to
      2013. Inclusion and exclusion criteria were defined a priori. Bibliographies of
      retrieved studies were searched by hand. Of the 8,854 publications retrieved, 104
      were included. RESULTS: Surgery by international charitable organizations is
      delivered under two, specialized hospitals and temporary platforms. Among the
      latter, short-term surgical missions were the most common and appeared beneficial
      when no other option was available. Compared to other platforms, however, worse
      results and a lack of cost-effectiveness curtailed their role. Self-contained
      temporary platforms that did not rely on local infrastructure showed promise,
      based on very few studies. Specialized hospitals provided effective treatment and
      appeared sustainable; cost-effectiveness evidence was limited. CONCLUSIONS:
      Because the charitable sector delivers surgery in vastly divergent ways,
      systematic review of these platforms has been difficult. This paper provides a
      framework from which to study these platforms for surgery in LMICs. Given the
      available evidence, self-contained temporary platforms and specialized surgical
      centers appear to provide more effective and cost-effective care than short-term
      surgical mission trips, except when no other delivery platform exists.

PMID- 24682280
TI  - New software tool automates and improves the accuracy of phylogenetic inference
      from next-generation sequencing data.

PMID- 24682281
TI  - Strong epistatic interactions within a single protein.
AB  - A central question in protein molecular evolution is whether an amino acid that
      occurs at a given site makes an independent contribution to fitness or whether
      its contribution depends on other amino acid sites in the protein sequence, a
      phenomenon known as intragenic epistasis. In the absence of intragenic epistasis,
      natural selection acts on a protein mutation independent of its genetic
      background, and the experimentally determined fitness for a mutation should be
      the same across all genetic backgrounds. We tested this hypothesis by using site
      directed mutagenesis to introduce a well-characterized deleterious single amino
      acid substitution in 56 different hepatitis C virus NS3 protease variants. The
      catalytic efficiency of the mutated proteases was determined and compared with
      the corresponding wild-type protein. Fitness effects ranged from lethality to
      significantly beneficial. Although primarily deleterious and lethal effects were
      observed (41 and 5 out of 56 tested variants, respectively), deleterious effects
      ranged from near neutral (-26.7% reduction of fitness) to near lethal (-98.5%).
      Our findings demonstrate that the introduced amino acid substitution has
      different fitness effects in different protein variants and provide independent
      support for the relevant role of intragenic epistasis in protein evolution. 

PMID- 24682282
TI  - Molecular characterization and evolution of a gene family encoding both female-
      and male-specific reproductive proteins in Drosophila.
AB  - Gene duplication is an important mechanism for the evolution of new reproductive
      proteins. However, in most cases, each resulting paralog continues to function
      within the same sex. To investigate the possibility that seminal fluid proteins
      arise through duplicates of female reproductive genes that become "co-opted" by
      males, we screened female reproductive genes in Drosophila melanogaster for cases
      of duplication in which one of the resulting paralogs produces a protein in males
      that is transferred to females during mating. We identified a set of three
      tandemly duplicated genes that encode secreted serine-type endopeptidase
      homologs, two of which are expressed primarily in the female reproductive tract
      (RT), whereas the third is expressed specifically in the male RT and encodes a
      seminal fluid protein. Evolutionary and gene expression analyses across
      Drosophila species suggest that this family arose from a single-copy gene that
      was female-specific; after duplication, one paralog evolved male-specific
      expression. Functional tests of knockdowns of each gene in D. melanogaster show
      that one female-expressed gene is essential for full fecundity, and both female
      expressed genes contribute singly or in combination to a female's propensity to
      remate. In contrast, knockdown of the male-expressed paralog had no significant
      effect on female fecundity or remating. These data are consistent with a model in
      which members of this gene family exert effects on females by acting on a common,
      female-expressed target. After duplication and male co-option of one paralog, the
      evolution of the interacting proteins could have resulted in differential
      strengths or effects of each paralog. 

PMID- 24682283
TI  - Correcting for differential transcript coverage reveals a strong relationship
      between alternative splicing and organism complexity.
AB  - What at the genomic level underlies organism complexity? Although several genomic
      features have been associated with organism complexity, in the case of
      alternative splicing, which has long been proposed to explain the variation in
      complexity, no such link has been established. Here, we analyzed over 39 million
      expressed sequence tags available for 47 eukaryotic species with fully sequenced
      genomes to obtain a comparable index of alternative splicing estimates, which
      corrects for the distorting effect of a variable number of transcripts per
      species--an important obstacle for comparative studies of alternative splicing.
      We find that alternative splicing has steadily increased over the last 1,400 My
      of eukaryotic evolution and is strongly associated with organism complexity,
      assayed as the number of cell types. Importantly, this association is not
      explained as a by-product of covariance between alternative splicing with other
      variables previously linked to complexity including gene content, protein length,
      proteome disorder, and protein interactivity. In addition, we found no evidence
      to suggest that the relationship of alternative splicing to cell type number is
      explained by drift due to reduced N(e) in more complex species. Taken together,
      our results firmly establish alternative splicing as a significant predictor of
      organism complexity and are, in principle, consistent with an important role of
      transcript diversification through alternative splicing as a means of determining
      a genome's functional information capacity.

PMID- 24682284
TI  - Evolutionary and molecular facts link the WWC protein family to Hippo signaling.
AB  - The scaffolding protein KIBRA (also called WWC1) is involved in the regulation of
      important intracellular transport processes and the establishment of cell
      polarity. Furthermore, KIBRA/WWC1 is an upstream regulator of the Hippo signaling
      pathway that controls cell proliferation and organ size in animals. KIBRA/WWC1
      represents only one member of the WWC protein family that also includes the
      highly similar proteins WWC2 and WWC3. Although the function of KIBRA/WWC1 was
      studied intensively in cells and animal models, the importance of WWC2 and WWC3
      was not yet elucidated. Here, we describe evolutionary, molecular, and functional
      aspects of the WWC family. We show that the WWC genes arose in the ancestor of
      bilateral animals (clades such as insects and vertebrates) from a single founder
      gene most similar to the present KIBRA/WWC1-like sequence of Drosophila. This
      situation was still maintained until the common ancestor of lancelet and
      vertebrates. In fish, a progenitor-like sequence of mammalian KIBRA/WWC1 and WWC2
      is expressed together with WWC3. Finally, in all tetrapods, the three family
      members, KIBRA/WWC1, WWC2, and WWC3, are found, except for a large genomic
      deletion including WWC3 in Mus musculus. At the molecular level, the highly
      conserved WWC proteins share a similar primary structure, the ability to form
      homo- and heterodimers and the interaction with a common set of binding proteins.
      Furthermore, all WWC proteins negatively regulate cell proliferation and organ
      growth due to a suppression of the transcriptional activity of YAP, the major
      effector of the Hippo pathway. 

PMID- 24682285
TI  - Progressive approval: a proposal for a new regulatory pathway for regenerative
      medicine.
AB  - To stimulate a broad discussion between academics, practicing physicians,
      corporate managers, and members of the regulatory community, we describe a
      proposal for a new regulatory pathway for human cell- and tissue-based products.
      The new components of the pathway are intended to accelerate patient access to a
      wide array of novel therapeutics, strengthen R&D infrastructure, and expand
      patient numbers and time lines for efficacy testing through a transparent and
      publicly accessible website for real-time reporting of outcome data and 5- to 10
      year, long-term follow-up.

PMID- 24682288
TI  - Authors' response to letter to the editor, "Effect of a single dose of propofol
      and lack of dextrose administration in a child with mitochondrial disease--a case
      report".

PMID- 24682286
TI  - Concise review: optimizing expansion of bone marrow mesenchymal stem/stromal
      cells for clinical applications.
AB  - Bone marrow-derived mesenchymal stem/stromal cells (MSCs) have demonstrated
      success in the clinical treatment of hematopoietic pathologies and cardiovascular
      disease and are the focus of treating other diseases of the musculoskeletal,
      digestive, integumentary, and nervous systems. However, during the requisite two
      dimensional (2D) expansion to achieve a clinically relevant number of cells, MSCs
      exhibit profound degeneration in progenitor potency. Proliferation, multilineage
      potential, and colony-forming efficiency are fundamental progenitor properties
      that are abrogated by extensive monolayer culture. To harness the robust
      therapeutic potential of MSCs, a consistent, rapid, and minimally detrimental
      expansion method is necessary. Alternative expansion efforts have exhibited
      promise in the ability to preserve MSC progenitor potency better than the 2D
      paradigm by mimicking features of the native bone marrow niche. MSCs have been
      successfully expanded when stimulated by growth factors, under reduced oxygen
      tension, and in three-dimensional bioreactors. MSC therapeutic value can be
      optimized for clinical applications by combining system inputs to tailor culture
      parameters for recapitulating the niche with probes that nondestructively monitor
      progenitor potency. The purpose of this review is to explore how modulations in
      the 2D paradigm affect MSC progenitor properties and to highlight recent efforts
      in alternative expansion techniques. 

PMID- 24682287
TI  - Concise review: lessons learned from clinical trials of gene therapy in monogenic
      immunodeficiency diseases.
AB  - Thirty years ago, retroviral transfer of genetic material into hematopoietic stem
      and progenitor cells (HSC/Ps) led to predictions that this technology would
      transform modern medicine [Nature 1983;305:556-558; Nature 1984;310:476-480].
      Studies in several immunodeficiency diseases in the past 15 years have
      demonstrated clear proof of principle that gene therapy can have long-lasting,
      potentially curative effects without the need to search for allogeneic donors and
      without risk of graft-versus-host disease. Improvement in gene transfer
      efficiency for target HSC/Ps brought to light issues of insertional mutagenesis
      caused by transfer vectors, resulting in oncogene transactivation and leukemias.
      Lessons from these adverse events have now led to a new generation of vectors,
      refinements in conditioning regimens, and manufacturing, which are paving the way
      for expanded applications of the current technology and recent emphasis on gene
      targeting/genome editing as the next advancements in the field. 

PMID- 24682289
TI  - High-dose glucocorticoid therapy in the management of seizures in neonatal
      incontinentia pigmenti: a case report.
AB  - Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation
      of IKBKG. This disorder has a classic dermatologic presentation, but neurologic
      involvement, with seizures and cortical infarction, can arise shortly after
      birth. There are no specific therapies available for the manifestations of
      incontinentia pigmenti. Here, we describe the clinical, electrographic, and
      neuroradiologic effect of systemic glucocorticoid therapy in a neonate with
      incontinentia pigmenti manifesting an epileptic encephalopathy. Treatment with
      dexamethasone led to a dramatic reduction in seizure activity and improvement in
      bullous lesions. A novel mutation in IKBKG is also reported. 

PMID- 24682290
TI  - Trends with corticosteroid use in males with Duchenne muscular dystrophy born
      1982-2001.
AB  - This study examines trends in corticosteroid use for males with Duchenne muscular
      dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular
      dystrophy family history. Firstborn males (n = 521) selected from a population
      based surveillance system of Duchenne muscular dystrophy were analyzed using
      Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males
      born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid
      initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black
      males used steroids less frequently and delayed initiation compared to white
      males. Compared to males without a Duchenne muscular dystrophy family history,
      males with known family history were half as likely to use steroids. Duration of
      steroid use increased over time and age at initiation decreased. Racial/ethnic
      disparities exist for steroid use and should be addressed to improve outcome and
      quality of life for boys with Duchenne muscular dystrophy. 

PMID- 24682291
TI  - Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical
      outcomes in acute decompensated heart failure: A meta-analysis of the literature.
AB  - BACKGROUND: In advanced congestive heart failure (CHF), intravenous (i.v.)
      inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been
      shown to not yield better clinical outcomes. In this scenario, the simultaneous
      administration of hypertonic saline solution (HSS) and furosemide may offer a
      more effective therapeutic option with a good safety profile. METHODS: Therefore,
      a meta-analysis was performed to compare combined therapy, consisting of i.v.
      furosemide plus concomitant administration of HSS, with i.v. furosemide alone for
      acute decompensated heart failure (ADHF). The outcomes we chose were all-cause
      mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight
      loss, and variation of serum creatinine. RESULTS: Based on five randomized
      controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus
      furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in
      all-cause mortality in patients treated with HSS plus furosemide was proven [RR =
      0.57; 95 % confidence interval (CI) = 0.44-0.74, p = 0.0003]. Likewise, combined
      therapy with HSS plus furosemide was shown to be associated with a reduced risk
      of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35-0.75, p = 0.001).
      Besides, combined therapy with HSS plus furosemide was found to be associated
      with a reduced length of hospital stay (p = 0.0002), greater weight loss (p <
      0.00001), and better preservation of renal function (p < 0.00001). CONCLUSION:
      HSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a
      better renal safety profile and improved clinical endpoints such as mortality and
      heart failure-related hospitalizations.

PMID- 24682292
TI  - Effect of gender differences on the regulation of renal ischemia-reperfusion
      induced inflammation in mice.
AB  - Inflammation is a key mediator of renal ischemia-reperfusion (IR) injury. Gender
      disparities have been reported in acute and chronic kidney disease. In
      particular, males are considered to be more susceptible to renal ischemic injury
      compared with females according to animal studies. The purpose of the present
      study was to investigate the effect of gender on the renal inflammatory response
      following acute renal IR injury in mice. Experiments were performed in male and
      female C57BL/6 mice. Two weeks prior to the study, castration or ovariectomy were
      performed and testosterone propionate (100 ug/kg) or 17beta-estradiol (100 ug/kg)
      was injected. Acute kidney injury (AKI) was induced by bilateral clamping of the
      renal pedicle for 23 min. Histological examination, western blot analysis and
      quantitative polymerase chain reaction were performed. In the acute renal IR
      injury model, the female mice were more resistant to kidney injury compared with
      the male mice. However, castration of the male mice reduced the levels of IR
      induced tubular injury and macrophage infiltration compared with those in the
      injured male mice. Supplementation of testosterone reversed this protective
      effect in the male AKI model. Depletion of estrogen in the female mice increased
      the levels of IR-induced tubular injury and macrophage infiltration compared with
      those in the injured female mice. However, supplementation of estrogen in the
      ovariectomized female mice attenuated the IR-induced tubular injury and reduced
      the levels of macrophage infiltration. The expression levels of inflammatory
      cytokines, including tumor necrosis factor-alpha, monocyte chemotactic protein-1,
      interferon-gamma and chemokine (C-C motif) ligand 17, were elevated in the male
      AKI mice compared with those in the control male mice, and were attenuated by
      castration. Estrogen depletion in the female mice significantly increased the
      expression levels of the renal inflammatory cytokines compared with those in the
      injured female mice, and were attenuated by estrogen supplementation in the
      ovariectomized female mice. These results suggested that the male gender confers
      greater susceptibility to IR renal injury due to an enhanced inflammatory
      response.

PMID- 24682293
TI  - Assessment of the treat-to-target strategy in patients with refractory rheumatoid
      arthritis. A prospective study on efficacy and safety in a Saudi population.
AB  - AIM: The goal of the present study was to prospectively assess the long-term
      clinical outcome of biologic modifying drug therapy in a population of Saudi
      rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: This is the first
      prospective, long-term report on the efficacy and safety of biologic therapy in
      Saudi RA patients. It is a single center, observational study with a follow-up
      period of 3 years. Enrolled were 120 biologic naive patients (94 women, 78.3 %;
      mean age 48.4 +/- 17.9 years, mean disease duration 7.3 +/- 3.9 years) with the
      diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to
      methotrexate and synthetic DMARDs. RESULTS: After 3 years, the mean Disease
      Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score,
      ESR, and CRP values improved significantly. Of the 99 patients completing the 3
      year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved
      low disease activity, and 11.1 % of patients had moderate to high activity
      scores. At the 3-year follow-up, 80 % of patients had no evidence of significant
      radiographic progression (achieved < 0.5 of the mean total Sharp score).
      Infections were reported in 11.7 % and significantly correlated with conjugate
      use of oral prednisolone at doses above 5 mg/day, with chest infections being the
      most common type of infection (6.7 %). CONCLUSION: The results of this study can
      be understood as real-life clinical experience displaying the incremental benefit
      of biologic therapy in refractory disease when it is added to other optimal
      strategies. The study showed satisfying clinical and functional benefit with
      considerable safety.

PMID- 24682294
TI  - Smoking bans are linked to reduction in preterm births and childhood asthma, says
      study.

PMID- 24682295
TI  - Development of an unmarked gene deletion system for the filamentous fungi
      Aspergillus niger and Talaromyces versatilis.
AB  - In this article, we present a method to delete genes in filamentous fungi that
      allows recycling of the selection marker and is efficient in a nonhomologous end
      joining (NHEJ)-proficient strain. We exemplify the approach by deletion of the
      gene encoding the transcriptional regulator XlnR in the fungus Aspergillus niger.
      To show the efficiency and advantages of the method, we deleted 8 other genes and
      constructed a double mutant in this species. Moreover, we showed that the same
      principle also functions in a different genus of filamentous fungus (Talaromyces
      versatilis, basionym Penicillium funiculosum). This technique will increase the
      versatility of the toolboxes for genome manipulation of model and industrially
      relevant fungi. 

PMID- 24682297
TI  - Directed evolution of unspecific peroxygenase from Agrocybe aegerita.
AB  - Unspecific peroxygenase (UPO) represents a new type of heme-thiolate enzyme with
      self-sufficient mono(per)oxygenase activity and many potential applications in
      organic synthesis. With a view to taking advantage of these properties, we
      subjected the Agrocybe aegerita UPO1-encoding gene to directed evolution in
      Saccharomyces cerevisiae. To promote functional expression, several different
      signal peptides were fused to the mature protein, and the resulting products were
      tested. Over 9,000 clones were screened using an ad hoc dual-colorimetric assay
      that assessed both peroxidative and oxygen transfer activities. After 5
      generations of directed evolution combined with hybrid approaches, 9 mutations
      were introduced that resulted in a 3,250-fold total activity improvement with no
      alteration in protein stability. A breakdown between secretion and catalytic
      activity was performed by replacing the native signal peptide of the original
      parental type with that of the evolved mutant; the evolved leader increased
      functional expression 27-fold, whereas an 18-fold improvement in the kcat/Km
      value for oxygen transfer activity was obtained. The evolved UPO1 was active and
      highly stable in the presence of organic cosolvents. Mutations in the hydrophobic
      core of the signal peptide contributed to enhance functional expression up to 8
      mg/liter, while catalytic efficiencies for peroxidative and oxygen transfer
      reactions were increased by several mutations in the vicinity of the heme access
      channel. Overall, the directed-evolution platform described is a valuable point
      of departure for the development of customized UPOs with improved features and
      for the study of structure-function relationships. 

PMID- 24682296
TI  - Nuclear localization of Haa1, which is linked to its phosphorylation status,
      mediates lactic acid tolerance in Saccharomyces cerevisiae.
AB  - Improvement of the lactic acid resistance of the yeast Saccharomyces cerevisiae
      is important for the application of the yeast in industrial production of lactic
      acid from renewable resources. However, we still do not know the precise
      mechanisms of the lactic acid adaptation response in yeast and, consequently,
      lack effective approaches for improving its lactic acid tolerance. To enhance our
      understanding of the adaptation response, we screened for S. cerevisiae genes
      that confer enhanced lactic acid resistance when present in multiple copies and
      identified the transcriptional factor Haa1 as conferring resistance to toxic
      levels of lactic acid when overexpressed. The enhanced tolerance probably results
      from increased expression of its target genes. When cells that expressed Haa1
      only from the endogenous promoter were exposed to lactic acid stress, the main
      subcellular localization of Haa1 changed from the cytoplasm to the nucleus within
      5 min. This nuclear accumulation induced upregulation of the Haa1 target genes
      YGP1, GPG1, and SPI1, while the degree of Haa1 phosphorylation observed under
      lactic acid-free conditions decreased. Disruption of the exportin gene MSN5 led
      to accumulation of Haa1 in the nucleus even when no lactic acid was present.
      Since Msn5 was reported to interact with Haa1 and preferentially exports
      phosphorylated cargo proteins, our results suggest that regulation of the
      subcellular localization of Haa1, together with alteration of its phosphorylation
      status, mediates the adaptation to lactic acid stress in yeast. 

PMID- 24682298
TI  - Spontaneously induced prophages in Lactobacillus gasseri contribute to horizontal
      gene transfer.
AB  - Lactobacillus gasseri is an endogenous species of the human gastrointestinal
      tract and vagina. With recent advances in microbial taxonomy, phylogenetics, and
      genomics, L. gasseri is recognized as an important commensal and is increasingly
      being used in probiotic formulations. L. gasseri strain ADH is lysogenic and
      harbors two inducible prophages. In this study, prophage adh was found to
      spontaneously induce in broth cultures to populations of ~ 10(7) PFU/ml by
      stationary phase. The adh prophage-cured ADH derivative NCK102 was found to
      harbor a new, second inducible phage, vB_Lga_jlb1 (jlb1). Phage jlb1 was
      sequenced and found to be highly similar to the closely related phage LgaI, which
      resides as two tandem prophages in the neotype strain L. gasseri ATCC 33323. The
      common occurrence of multiple prophages in L. gasseri genomes, their propensity
      for spontaneous induction, and the high degree of homology among phages within
      multiple species of Lactobacillus suggest that temperate bacteriophages likely
      contribute to horizontal gene transfer (HGT) in commensal lactobacilli. In this
      study, the host ranges of phages adh and jlb1 were determined against 16 L.
      gasseri strains. The transduction range and the rate of spontaneous transduction
      were investigated in coculture experiments to ascertain the degree to which
      prophages can promote HGT among a variety of commensal and probiotic
      lactobacilli. Both adh and jlb1 particles were confirmed to mediate plasmid
      transfer. As many as ~10(3) spontaneous transductants/ml were obtained. HGT by
      transducing phages of commensal lactobacilli may have a significant impact on the
      evolution of bacteria within the human microbiota.

PMID- 24682299
TI  - Microbial metabolic potential for carbon degradation and nutrient (nitrogen and
      phosphorus) acquisition in an ombrotrophic peatland.
AB  - This study integrated metagenomic and nuclear magnetic resonance (NMR)
      spectroscopic approaches to investigate microbial metabolic potential for organic
      matter decomposition and nitrogen (N) and phosphorus (P) acquisition in soils of
      an ombrotrophic peatland in the Marcell Experimental Forest (MEF), Minnesota,
      USA. This analysis revealed vertical stratification in key enzymatic pathways and
      taxa containing these pathways. Metagenomic analyses revealed that genes encoding
      laccases and dioxygenases, involved in aromatic compound degradation, declined in
      relative abundance with depth, while the relative abundance of genes encoding
      metabolism of amino sugars and all four saccharide groups increased with depth in
      parallel with a 50% reduction in carbohydrate content. Most Cu-oxidases were
      closely related to genes from Proteobacteria and Acidobacteria, and type 4
      laccase-like Cu-oxidase genes were >8 times more abundant than type 3 genes,
      suggesting an important and overlooked role for type 4 Cu-oxidase in phenolic
      compound degradation. Genes associated with sulfate reduction and methanogenesis
      were the most abundant anaerobic respiration genes in these systems, with low
      levels of detection observed for genes of denitrification and Fe(III) reduction.
      Fermentation genes increased in relative abundance with depth and were largely
      affiliated with Syntrophobacter. Methylocystaceae-like small-subunit (SSU) rRNA
      genes, pmoA, and mmoX genes were more abundant among methanotrophs. Genes
      encoding N2 fixation, P uptake, and P regulons were significantly enriched in the
      surface peat and in comparison to other ecosystems, indicating N and P
      limitation. Persistence of inorganic orthophosphate throughout the peat profile
      in this P-limiting environment indicates that P may be bound to recalcitrant
      organic compounds, thus limiting P bioavailability in the subsurface. Comparative
      metagenomic analysis revealed a high metabolic potential for P transport and
      starvation, N2 fixation, and oligosaccharide degradation at MEF relative to other
      wetland and soil environments, consistent with the nutrient-poor and carbohydrate
      rich conditions found in this Sphagnum-dominated boreal peatland. 

PMID- 24682300
TI  - Microbial community stratification linked to utilization of carbohydrates and
      phosphorus limitation in a boreal peatland at Marcell Experimental Forest,
      Minnesota, USA.
AB  - This study investigated the abundance, distribution, and composition of microbial
      communities at the watershed scale in a boreal peatland within the Marcell
      Experimental Forest (MEF), Minnesota, USA. Through a close coupling of next
      generation sequencing, biogeochemistry, and advanced analytical chemistry, a
      biogeochemical hot spot was revealed in the mesotelm (30- to 50-cm depth) as a
      pronounced shift in microbial community composition in parallel with elevated
      peat decomposition. The relative abundance of Acidobacteria and the
      Syntrophobacteraceae, including known hydrocarbon-utilizing genera, was
      positively correlated with carbohydrate and organic acid content, showing a
      maximum in the mesotelm. The abundance of Archaea (primarily crenarchaeal groups
      1.1c and 1.3) increased with depth, reaching up to 60% of total small-subunit
      (SSU) rRNA gene sequences in the deep peat below the 75-cm depth. Stable isotope
      geochemistry and potential rates of methane production paralleled vertical
      changes in methanogen community composition to indicate a predominance of
      acetoclastic methanogenesis mediated by the Methanosarcinales in the mesotelm,
      while hydrogen-utilizing methanogens predominated in the deeper catotelm. RNA
      derived pyrosequence libraries corroborated DNA sequence data to indicate that
      the above-mentioned microbial groups are metabolically active in the mid-depth
      zone. Fungi showed a maximum in rRNA gene abundance above the 30-cm depth, which
      comprised only an average of 0.1% of total bacterial and archaeal rRNA gene
      abundance, indicating prokaryotic dominance. Ratios of C to P enzyme activities
      approached 0.5 at the acrotelm and catotelm, indicating phosphorus limitation. In
      contrast, P limitation pressure appeared to be relieved in the mesotelm, likely
      due to P solubilization by microbial production of organic acids and C-P lyases.
      Based on path analysis and the modeling of community spatial turnover, we
      hypothesize that P limitation outweighs N limitation at MEF, and microbial
      communities are structured by the dominant shrub, Chamaedaphne calyculata, which
      may act as a carbon source for major consumers in the peatland. 

PMID- 24682301
TI  - Development of a homologous expression system for and systematic site-directed
      mutagenesis analysis of thurincin H, a bacteriocin produced by Bacillus
      thuringiensis SF361.
AB  - Thurincin H is an antimicrobial peptide produced by Bacillus thuringiensis SF361.
      With a helical back bone, the 31 amino acids of thurincin H form a hairpin
      structure maintained by four pairs of very unique sulfur-to-alpha-carbon
      thioether bonds. The production of thurincin H depends on a putative gene cluster
      containing 10 open reading frames. The gene cluster includes three tandem
      structural genes (thnA1, thnA2, and thnA3) encoding three identical 40-amino-acid
      thurincin H prepeptides and seven other genes putatively responsible for
      prepeptide processing, regulation, modification, exportation, and self-immunity.
      A homologous thurincin H expression system was developed by transforming a
      thurincin H-deficient host with a novel expression vector, pGW133. The host,
      designated B. thuringiensis SF361 DeltathnA1 DeltathnA2 DeltathnA3, was
      constructed by deletion of the three tandem structural genes from the chromosome
      of the natural thurincin H producer. The thurincin H expression vector pGW133 was
      constructed by cloning the thurincin H native promoter, thnA1, and a Cry protein
      terminator into the Escherichia coli-B. thuringiensis shuttle vector pHT315.
      Thirty-three different pGW133 variants, each containing a different point
      mutation in the thnA1 gene, were generated and separately transformed into B.
      thuringiensis SF361 DeltathnA1 DeltathnA2 DeltathnA3. Those site-directed mutants
      contained either a single radical or conservative amino acid substitution on the
      thioether linkage-forming positions or a radical substitution on all other
      nonalanine amino acids. The bacteriocin activities of B. thuringiensis SF361
      DeltathnA1 DeltathnA2 DeltathnA3 carrying different pGW133 variants against three
      different indicator strains were subsequently compared.

PMID- 24682302
TI  - Genes of the N-methylglutamate pathway are essential for growth of
      Methylobacterium extorquens DM4 with monomethylamine.
AB  - Monomethylamine (MMA, CH3NH2) can be used as a carbon and nitrogen source by many
      methylotrophic bacteria. Methylobacterium extorquens DM4 lacks the MMA
      dehydrogenase encoded by mau genes, which in M. extorquens AM1 is essential for
      growth on MMA. Identification and characterization of minitransposon mutants with
      an MMA-dependent phenotype showed that strain DM4 grows with MMA as the sole
      source of carbon, energy, and nitrogen by the N-methylglutamate (NMG) pathway.
      Independent mutations were found in a chromosomal region containing the genes
      gmaS, mgsABC, and mgdABCD for the three enzymes of the pathway, gamma
      glutamylmethylamide (GMA) synthetase, NMG synthase, and NMG dehydrogenase,
      respectively. Reverse transcription-PCR confirmed the operonic structure of the
      two divergent gene clusters mgsABC-gmaS and mgdABCD and their induction during
      growth with MMA. The genes mgdABCD and mgsABC were found to be essential for
      utilization of MMA as a carbon and nitrogen source. The gene gmaS was essential
      for MMA utilization as a carbon source, but residual growth of mutant DM4gmaS
      growing with succinate and MMA as a nitrogen source was observed. Plasmid copies
      of gmaS and the gmaS homolog METDI4690, which encodes a protein 39% identical to
      GMA synthetase, fully restored the ability of mutants DM4gmaS and
      DM4gmaSDeltametdi4690 to use MMA as a carbon and nitrogen source. Similarly,
      chemically synthesized GMA, the product of GMA synthetase, could be used as a
      nitrogen source for growth in the wild-type strain, as well as in DM4gmaS and
      DM4gmaSDeltametdi4690 mutants. The NADH:ubiquinone oxidoreductase respiratory
      complex component NuoG was also found to be essential for growth with MMA as a
      carbon source. 

PMID- 24682303
TI  - Raman spectroscopy of microbial pigments.
AB  - Raman spectroscopy is a rapid nondestructive technique providing spectroscopic
      and structural information on both organic and inorganic molecular compounds.
      Extensive applications for the method in the characterization of pigments have
      been found. Due to the high sensitivity of Raman spectroscopy for the detection
      of chlorophylls, carotenoids, scytonemin, and a range of other pigments found in
      the microbial world, it is an excellent technique to monitor the presence of such
      pigments, both in pure cultures and in environmental samples. Miniaturized
      portable handheld instruments are available; these instruments can be used to
      detect pigments in microbiological samples of different types and origins under
      field conditions. 

PMID- 24682304
TI  - Utility of the clostridial site-specific recombinase TnpX to clone toxic-product
      encoding genes and selectively remove genomic DNA fragments.
AB  - TnpX is a site-specific recombinase responsible for the excision and insertion of
      the transposons Tn4451 and Tn4453 in Clostridium perfringens and Clostridium
      difficile, respectively. Here, we exploit phenotypic features of TnpX to
      facilitate genetic mutagenesis and complementation studies. Genetic manipulation
      of bacteria often relies on the use of antibiotic resistance genes; however, a
      limited number are available for use in the clostridia. The ability of TnpX to
      recognize and excise specific DNA fragments was exploited here as the basis of an
      antibiotic resistance marker recycling system, specifically to remove antibiotic
      resistance genes from plasmids in Escherichia coli and from marked chromosomal C.
      perfringens mutants. This methodology enabled the construction of a C.
      perfringens plc virR double mutant by allowing the removal and subsequent reuse
      of the same resistance gene to construct a second mutation. Genetic
      complementation can be challenging when the gene of interest encodes a product
      toxic to E. coli. We show that TnpX represses expression from its own promoter,
      PattCI, which can be exploited to facilitate the cloning of recalcitrant genes in
      E. coli for subsequent expression in the heterologous host C. perfringens.
      Importantly, this technology expands the repertoire of tools available for the
      genetic manipulation of the clostridia.

PMID- 24682305
TI  - Resilience of the natural phyllosphere microbiota of the grapevine to chemical
      and biological pesticides.
AB  - The phyllosphere is colonized by complex microbial communities, which are adapted
      to the harsh habitat. Although the role and ecology of nonpathogenic
      microorganisms of the phyllosphere are only partially understood, leaf microbiota
      could have a beneficial role in plant growth and health. Pesticides and
      biocontrol agents are frequently applied to grapevines, but the impact on
      nontarget microorganisms of the phyllosphere has been marginally considered. In
      this study, we investigated the effect of a chemical fungicide (penconazole) and
      a biological control agent (Lysobacter capsici AZ78) on the leaf microbiota of
      the grapevine at three locations. Amplicons of the 16S rRNA gene and of the
      internal transcribed spacer were sequenced for bacterial and fungal
      identification, respectively. Pyrosequencing analysis revealed that the richness
      and diversity of bacterial and fungal populations were only minimally affected by
      the chemical and biological treatments tested, and they mainly differed according
      to grapevine locations. Indigenous microbial communities of the phyllosphere are
      adapted to environmental and biotic factors in the areas where the grapevines are
      grown, and they are resilient to the treatments tested. The biocontrol properties
      of phyllosphere communities against downy mildew differed among grapevine
      locations and were not affected by treatments, suggesting that biocontrol
      communities could be improved with agronomic practices to enrich beneficial
      populations in vineyards.

PMID- 24682307
TI  - Interstitial lung disease in patients with hepatopulmonary syndrome: a case
      series and new observations.
AB  - Hepatopulmonary syndrome (HPS) is characterized by impaired oxygenation due to
      pulmonary vascular dilatation in patients with end-stage liver disease. At our
      center, we identified 29 patients who were listed for liver transplantation (LT)
      with a model for end-stage liver disease exception for HPS between 2001 and 2012.
      Five of these patients were found to have concurrent interstitial lung disease
      (ILD). The chest high-resolution computed-tomography demonstrated ground-glass
      opacities and subpleural reticulation, most consistent with nonspecific
      interstitial pneumonia (NSIP). All four of our patients who underwent LT
      experienced prolonged hypoxemia postoperatively, with one surgery-related death.
      However, the three surviving patients had eventual resolution of their hypoxemia
      with no evidence of ILD progression. In conclusion, we report a high prevalence
      of ILD, most consistent with NSIP, among patients with HPS. Although there may be
      increased perioperative risks, the finding of ILD in patients with HPS should not
      be considered an absolute contraindication to LT. 

PMID- 24682306
TI  - HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional
      phenotype of fibro-adipogenic progenitors in dystrophic muscles.
AB  - Fibro-adipogenic progenitors (FAPs) are important components of the skeletal
      muscle regenerative environment. Whether FAPs support muscle regeneration or
      promote fibro-adipogenic degeneration is emerging as a key determinant in the
      pathogenesis of muscular diseases, including Duchenne muscular dystrophy (DMD).
      However, the molecular mechanism that controls FAP lineage commitment and
      activity is currently unknown. We show here that an HDAC-myomiR-BAF60 variant
      network regulates the fate of FAPs in dystrophic muscles of mdx mice.
      Combinatorial analysis of gene expression microarray, genome-wide chromatin
      remodeling by nuclease accessibility (NA) combined with next-generation
      sequencing (NA-seq), small RNA sequencing (RNA-seq), and microRNA (miR) high
      throughput screening (HTS) against SWI/SNF BAF60 variants revealed that HDAC
      inhibitors (HDACis) derepress a "latent" myogenic program in FAPs from dystrophic
      muscles at early stages of disease. Specifically, HDAC inhibition induces two
      core components of the myogenic transcriptional machinery, MYOD and BAF60C, and
      up-regulates the myogenic miRs (myomiRs) (miR-1.2, miR-133, and miR-206), which
      target the alternative BAF60 variants BAF60A and BAF60B, ultimately directing
      promyogenic differentiation while suppressing the fibro-adipogenic phenotype. In
      contrast, FAPs from late stage dystrophic muscles are resistant to HDACi-induced
      chromatin remodeling at myogenic loci and fail to activate the promyogenic
      phenotype. These results reveal a previously unappreciated disease stage-specific
      bipotency of mesenchimal cells within the regenerative environment of dystrophic
      muscles. Resolution of such bipotency by epigenetic intervention with HDACis
      provides a molecular rationale for the in situ reprogramming of target cells to
      promote therapeutic regeneration of dystrophic muscles.

PMID- 24682308
TI  - Differences in videofluoroscopic swallowing study (VFSS) findings according to
      the vascular territory involved in stroke.
AB  - Dysphagia affects up to half of stroke patients and increases the risk of
      pneumonia and fatal outcomes. In order to assess swallowing difficulty,
      videofluoroscopic swallowing study (VFSS) has traditionally been the gold
      standard. The purpose of this study was to compare the patterns of post-stroke
      swallowing difficulties according to the vascular territories involved in the
      stroke. One hundred and three patients who were diagnosed with first ischemic
      stroke by brain magnetic resonance imaging and had swallowing difficulty were
      included in this study. Location of the stroke was classified into three groups:
      territorial anterior infarcts (TAI) (n = 62), territorial posterior infarcts
      (TPI) (n = 19) and white matter disease (WMD) (n = 22). Oral cavity residue
      existed significantly in the TAI group more than in any other groups (P = 0.017).
      The WMD group showed more residue in the valleculae (P = 0.002) and the TPI group
      showed more residue in the pyriform sinuses (P = 0.001). The oral transit time,
      pharyngeal delay time and pharyngeal transit time did not show significant
      differences among the groups with swallowing of both thick and thin liquids.
      Penetration and aspiration were more frequent in the TPI group (P < 0.05) with
      swallowing of both thick and thin liquids. The results suggest that TAI is more
      related to oral phase dysfunction and TPI is more related to pharyngeal
      dysfunction. In ischemic stroke, patterns of swallowing difficulty may differ
      according to the vascular territory involved and this should be considered in the
      management of post-stroke dysphagia. 

PMID- 24682309
TI  - Effects of water-saving irrigation on emissions of greenhouse gases and
      prokaryotic communities in rice paddy soil.
AB  - The effects of water-saving irrigation on emissions of greenhouse gases and soil
      prokaryotic communities were investigated in an experimental rice field. The
      water layer was kept at 1-2 cm in the water-saving (WS) irrigation treatment and
      at 6 cm in the continuous flooding (CF) irrigation treatment. WS irrigation
      decreased CH(4) emissions by 78 % and increased N(2)O emissions by 533 %,
      resulting in 78 % reduction of global warming potential compared to the CF
      irrigation. WS irrigation did not affect the abundance or phylogenetic
      distribution of bacterial/archaeal 16S rRNA genes and the abundance of
      bacterial/archaeal 16S rRNAs. The transcript abundance of CH(4) emission-related
      genes generally followed CH(4) emission patterns, but the difference in abundance
      between mcrA transcripts and amoA/pmoA transcripts best described the differences
      in CH(4) emissions between the two irrigation practices. WS irrigation increased
      the relative abundance of 16S rRNAs and functional gene transcripts associated
      with Anaeromyxobacter and Methylocystis spp., suggesting that their activities
      might be important in emissions of the greenhouse gases. The N(2)O emission
      patterns were not reflected in the abundance of N(2)O emission-related genes and
      transcripts. We showed that the alternative irrigation practice was effective for
      mitigating greenhouse gas emissions from rice fields and that it did not affect
      the overall size and structure of the soil prokaryotic community but did affect
      the activity of some groups.

PMID- 24682310
TI  - Introduction of an acute surgical unit: comparison of performance indicators and
      outcomes for operative management of acute appendicitis.
AB  - BACKGROUND: The Acute Surgical Unit (ASU) is a recent change in management of
      acute general surgical patients in hospitals worldwide. In contrast to
      traditional management of acute surgical presentations by a rotating on-call
      system, ASUs are shown to deliver improved efficiency and patient outcomes. This
      study investigated the impact of an ASU on operative management of appendicitis,
      the most common acute surgical presentation, by comparing performance indicators
      and patient outcomes prior to and after introduction of an ASU at the Gold Coast
      Hospital, Queensland, Australia. METHODS: A retrospective study of patients
      admitted from the Emergency Department (ED) and who underwent emergency
      appendectomy from February 2010 to January 2011 (pre-ASU) and after introduction
      of the ASU from February 2011 to January 2012 (post-ASU). A total of 548 patients
      underwent appendectomy between February 2010 and January 2012, comprising 247 pre
      ASU and 301 post-ASU patients. RESULTS: Significant improvements were
      demonstrated: reduced time to surgical review, fewer complications arising from
      operations commencing during ASU in-hours, and more appendectomies performed
      during the daytime attended by the consultant. There was no significant
      difference in total cost of admission or total admission length of stay.
      CONCLUSIONS: This study demonstrated that ASUs have potential to significantly
      improve the outcomes for operative management of acute appendicitis compared to
      the traditional on-call model. The impact of the ASU was limited by access to
      theaters and restricted ASU operation hours. Further investigation of site
      specific determinants could be beneficial to optimize this new model of acute
      surgical care.

PMID- 24682311
TI  - Up-regulation of neutrophil gelatinase-associated lipocalin in colorectal cancer
      predicts poor patient survival.
AB  - BACKGROUND: Lipocalin-2 (Lcn-2) is expressed in human neutrophils and epithelial
      cells, particularly in the presence of inflammation or cancer. It was shown to be
      highly expressed in various human cancers. Increased protein levels were
      associated with decreased survival of patients with breast or gastric cancer. The
      main focus of this work was to analyze the implication of Lcn-2 up-regulation in
      the genesis of colon cancer. METHODS: Expression of Lcn-2 was analyzed in
      colorectal carcinoma cell lines, paired colorectal carcinoma tissues, and regular
      mucosa by Western blot analysis. Lcn-2 immunohistochemical staining was performed
      in 192 colorectal carcinoma resection specimens and correlated with
      clinicopathologic parameters. RESULTS: Western blot analysis of colorectal
      carcinoma tissues demonstrated Lcn-2 overexpression in carcinomas as compared
      with regular mucosa. Immunohistochemical staining revealed Lcn-2 expression in
      179 (93.2%) colorectal carcinoma tissues. Intense immunoreactivity was
      significantly correlated with metastasis (p = 0.042) and UICC stage (p = 0.027).
      Survival analysis according to the Kaplan-Meier method revealed a significant
      association between Lcn-2 overexpressing tumors and overall survival (p < 0.001)
      and disease-free survival (p < 0.001). CONCLUSIONS: Our data provide evidence
      that Lcn-2 expression is up-regulated with tumor progression and was found to be
      a predictor of overall survival.

PMID- 24682312
TI  - Pulmonary function after lobectomy versus segmentectomy in patients with stage I
      non-small cell lung cancer.
AB  - BACKGROUND: Several reports have shown that segmentectomy is superior to
      lobectomy for preservation of postoperative pulmonary function. The purpose of
      this study was to characterize the relationship between pulmonary function and
      the volume of the resected lung in patients undergoing segmentectomy or
      lobectomy. METHODS: Patients undergoing open lobectomy (n = 126) and open
      segmentectomy (n = 52) for stage I non-small cell lung cancer were analyzed
      retrospectively. Pulmonary function testing, including vital capacity (VC) and
      forced expiratory volume in 1 second (FEV1), was performed preoperatively and at
      1 and 6 months postoperatively. RESULTS: The postoperative reduction of VC and
      FEV1, as indicated by the postoperative value/preoperative value, at 6 months
      after surgery was significantly less in the segmentectomy group than in the
      lobectomy group. However, the standardized functional loss ratio, as expressed by
      [(measured postoperative value)-(predicted postoperative value)] / (predicted
      postoperative value) * 100 (%), at 1 month after surgery was significantly lower
      in the segmentectomy group than in the lobectomy group. No significant difference
      in the standardized functional loss ratio was seen at 6 months postoperatively.
      CONCLUSIONS: Pulmonary function at 6 months after surgery is better after
      segmental resection than after lobectomy. However, the absolute value of
      pulmonary function did not reach the predicted-postoperative value at 1 month
      after surgery. Thus, when segmentectomy is performed, clinicians should be aware
      that early postoperative pulmonary function may be significantly less than the
      expected value.

PMID- 24682313
TI  - Postoperative nonsteroidal anti-inflammatory drugs and risk of anastomotic leak:
      meta-analysis of clinical and experimental studies.
AB  - BACKGROUND: Enhanced recovery programs following colorectal resection recommend
      the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as part of multimodal
      analgesia. The present study aimed to assess whether postoperative NSAID use
      increased the risk of anastomotic leak. METHODS: A systematic review of published
      literature was performed for studies comparing anastomotic leak following NSAID
      administration versus control. Meta-analysis was conducted for studies in human
      patients and experimental animal models. The primary endpoint was anastomotic
      leak. RESULTS: The final analysis included 8 studies in humans and 12
      experimental animal studies. Use of NSAIDs was significantly associated with
      anastomotic leak in humans (8 studies, 4,464 patients, odds ratio [OR] 2.14; p <
      0.001). This effect was seen with nonselective NSAIDs (6 studies, 3,074 patients,
      OR 2.37; p < 0.001), but not with selective NSAIDs (4 studies, 1,223 patients, OR
      2.32; p = 0.170). There was strong evidence of selection bias from all clinical
      studies, with additional inconsistent definitions and outcomes assessment. From
      experimental animal models, anastomotic leak was more likely with NSAID use (ten
      studies, 575 animals, OR 9.51; p < 0.001). Bursting pressures at day 7 were
      significantly lower in NSAID versus controls (7 studies, 168 animals, weighted
      mean difference -35.7 mmHg; p < 0.001). CONCLUSIONS: Emerging data strongly
      suggest that postoperative NSAIDs are linked to anastomotic leak, although most
      studies are flawed and may be describing pre-existing selection bias. However,
      when combined with experimental data, these increasing concerns suggest caution
      is needed when prescribing NSAIDs to patients with pre-existing risk factors for
      leak, until more definitive evidence emerges.

PMID- 24682314
TI  - Improving trauma care in low- and middle-income countries by implementing a
      standardized trauma protocol.
AB  - BACKGROUND: Standardized trauma protocols (STPs) have reduced morbidity and
      mortality in mature trauma systems. Most hospitals in low- and middle-income
      countries (LMICs) have not yet implemented such protocols, often due to financial
      and logistic limitations. We report preliminary findings from a trauma quality
      improvement (QI) initiative, using and evaluating the impact of a low-cost STP in
      an LMIC university hospital. METHODS: We developed an STP based on generally
      accepted best practices and damage control resuscitation. It was designed for the
      resources available at the test institution. The Neiva University Hospital (NUH)
      is a tertiary care hospital and level I trauma center in Neiva, Colombia. As in
      most LMIC hospitals, there was no trauma information data system at NUH.
      Therefore, we adapted an administrative electronic database to capture clinically
      relevant information of adult patients who were hospitalized or died in the
      emergency department (ED) between August 2010 and June 2012 with an International
      Classification of Diseases, 10th revision (ICD-10) diagnoses indicating trauma
      (S00-Y98). Interventions that were recommended in the STP were compared in these
      two groups. Length of hospital stay (LOS) and mortality were also examined.
      RESULTS: A total of 4,324 patients were included, of whom, 2,457 patients were in
      the pre-protocol period and 1,867 were in the post-protocol period. The use of
      several interventions increased: blood product transfusions in the ED (1.0 vs.
      2.7%; p < 0.001), use of hypertonic fluids in hypotensive patients (3.2 vs. 8.9
      %; p < 0.001), placement of Foley catheters (11.1 vs. 13.8%; p = 0.007), arterial
      blood gas draws (16.6 vs. 26.4%; p < 0.001), tetanus vaccinations (19.3 vs.
      26.0%; p < 0.001), placement of multiple large bore peripheral catheters (29.5
      vs. 34.7%; p < 0.001), prophylactic antibiotics (34.9 vs. 38.0%; p = 0.035), and
      the use of analgesics (64.5 vs. 68.0%; p = 0.016). Other interventions also
      trended upwards. Length of stay (LOS) decreased for both surgical and non
      surgical patients (surgical 13.4 vs. 11.8 days; p = 0.017; non-surgical 4.4 vs.
      3.8 days; p = 0.059). All-cause mortality of trauma patients decreased (3.9 vs.
      2.9%; p = 0.088). CONCLUSIONS: The institution of an STP at a university hospital
      in an LMIC has increased the use of vital interventions while decreasing overall
      LOS for all-cause trauma patients.

PMID- 24682315
TI  - Limited potential for prevention of emergency surgery for femoral hernia.
AB  - BACKGROUND: Femoral hernias are frequently operated on as an emergency. Emergency
      procedures for femoral hernia are associated with an almost tenfold increase in
      postoperative mortality, while no increase is seen for elective procedures,
      compared with a background population. OBJECTIVE: The aim of this study was to
      compare whether symptoms from femoral hernias and healthcare contacts prior to
      surgery differ between patients who have elective and patients who have emergency
      surgery. METHODS: A total of 1,967 individuals operated on for a femoral hernia
      over 1997-2006 were sent a questionnaire on symptoms experienced and contact with
      the healthcare system prior to surgery for their hernia. Answers were matched
      with data from the Swedish Hernia Register. RESULTS: A total of 1,441 (73.3%)
      patients responded. Awareness of their hernia prior to surgery was denied by
      53.3% (231/433) of those who underwent an emergency procedure. Of the emergency
      operated patients, 31.3% (135/432) negated symptoms in the affected groin prior
      to surgery and 22.2% (96/432) had neither groin nor other symptoms. Elective
      patients had a considerably higher contact frequency with their general
      practitioner, as well as the surgical outpatient department, prior to surgery
      compared with patients undergoing emergency surgery (p < 0.001). CONCLUSIONS:
      Patients who have elective and patients who have emergency femoral hernia surgery
      differ in previous symptoms and healthcare contacts. Patients who need emergency
      surgery are often unaware of their hernia and frequently completely asymptomatic
      prior to incarceration. Early diagnosis and expedient surgery is warranted, but
      the lack of symptoms hinders earlier detection and intervention in most cases.

PMID- 24682316
TI  - Effect of the N-butanoyl glutathione (GSH) derivative and acyclovir on HSV-1
      replication and Th1 cytokine expression in human macrophages.
AB  - Macrophages are an important defense against in vivo herpes simplex virus (HSV)
      infection by early cytokine secretion; however, they can be infected by HSV-1 and
      they may be compromised in their ability to produce cytokines. In this paper, we
      studied the expression of two Th1 cytokines, interleukin (IL)-12 and IL-27, upon
      HSV-1 infection of human macrophages, and how it is regulated by treatment with
      two antiviral drugs exerting their anti-HSV-1 activity through different
      mechanisms of action. We found that infection does not alter intra-macrophage
      thiol content, while it induces mRNA expression of IL-12 p35 and IL-12 p40 as
      well as of IL-27 p28 and IL-27 EBI3, as revealed by RT-PCR. The increased
      expression of mRNA is accompanied by increased production of IL-12 p40 and IL-27
      p28 protein, as detected in the culture supernatants by ELISA. The two antiviral
      drugs tested were acyclovir (ACV), commonly used to treat herpes virus
      infections, and an N-butanoyl glutathione (GSH) derivative, GSH-C4. While ACV
      inhibits viral DNA polymerase, GSH-C4 inhibits virus replication by interfering
      with protein folding and maturation of viral particles. Indeed, GSH-C4, altering
      the intracellular redox state, may modulate the Th1/Th2 balance favoring Th1-type
      response. Our data show that both drugs inhibit HSV-1 replication in macrophages,
      without significantly affecting cytokine mRNA levels. Nonetheless, lower levels
      of IL-12 p40 and IL-27 p28 proteins were found in the supernatants of macrophages
      treated with either GSH-C4 or ACV, likely as an indirect consequence of inhibited
      HSV-1 replication. 

PMID- 24682317
TI  - [Endophthalmitis, liver abscess, and cerebral and pulmonary emboli in a 48-year
      old Vietnamese man].
AB  - We present the case of a 48-year-old Vietnamese man with endophthalmitis, liver
      abscess, and pulmonary and cerebral septic emboli. Klebsiella pneumoniae was
      isolated as the causative organism; there were no laboratory findings suggestive
      of invasive fungal infection. Klebsiella pneumoniae invasive syndrome is a rare
      disease in Germany. This case report exemplifies the necessity of a dedicated
      diagnostic approach that takes into consideration factors such as ethnic origin
      and accompanying diseases of the patient. 

PMID- 24682318
TI  - Resveratrol attenuates the inflammatory reaction induced by ischemia/reperfusion
      in the rat heart.
AB  - The role of resveratrol (Res) in inflammation induced by ischemia/reperfusion is
      not well understood. The aim of the present study was to investigate whether Res
      modulates neutrophil accumulation and tumor necrosis factor-alpha (TNF-alpha)
      induction in an ischemia/reperfusion-injured rat heart model. The rats were
      randomly exposed to sham surgery, myocardial ischemia/reperfusion (MI/R) alone,
      MI/R + Res, MI/R + Res + L-NG-nitroarginine methyl ester (L-NAME) and MI/R + Res
      + methylene blue (MB). The results demonstrated that compared with MI/R, Res
      reduced the myocardial infarct area, myocardial myeloperoxidase levels, serum
      creatinine kinase and lactate dehydrogenase levels, and serum and myocardial TNF
      alpha production. All the effects of Res demonstrated were inhibited by L-NAME (a
      nitric oxide (NO) synthase inhibitor) and MB [a cyclic guanosine monophosphate
      (cGMP) inhibitor]. Thus, Res produces cardioprotective and anti-inflammatory
      effects. These effects may be associated with an increase in NO production, the
      inhibition of neutrophil accumulation, TNF-alpha induction and cGMP signaling
      pathways in myocardium subjected to MI/R.

PMID- 24682319
TI  - Etanercept reduces symptoms and severity of psoriasis after cessation of
      cyclosporine therapy: results of the SCORE study.
AB  - Cyclosporine is an established therapy for psoriasis that provides rapid relief
      of symptoms but has long-term toxic side effects. The objective of this study was
      to demonstrate the efficacy of etanercept as replacement therapy for cyclosporine
      in patients with moderate-to-severe plaque psoriasis. Patients with plaque
      psoriasis were given cyclosporine 5 mg/kg/day until achievement of PASI50 at
      which point cyclosporine was tapered to 0 over 6 weeks. At week 6, patients were
      randomised (1:1) to receive etanercept (50 mg/week) or placebo for an additional
      24 weeks. Patients in the etanercept group (n = 58) experienced a reduction of 
      1.1 in mean PASI score (p = 0.233 vs. cyclosporine) at week 30; patients in the
      placebo group (n = 62) had mean PASI increase of 3.7 (p < 0.001 vs.
      cyclosporine). The incidence of patients reporting any adverse events was not
      significant between groups (77% etanercept, 74% placebo; p = 0.675). Etanercept
      demonstrated higher efficacy and good tolerability as replacement therapy for
      cyclosporine in plaque psoriasis. 

PMID- 24682320
TI  - The lived experience of teaching about race in cultural nursing education.
AB  - PURPOSE: Some nursing scholars assert that race and racism require a more
      explicit focus in cultural nursing education if the profession is to positively
      impact health care disparities. This study explored what White BSN cultural
      educators think, believe, and teach about race, racism, and antiracism. METHOD:
      Phenomenological methods were used to analyze interview data from 10 White BSN
      faculty members who taught cultural content. FINDINGS: Four themes were
      identified: living and learning in White spaces, a personal journey toward
      antiracism, values transformed through personal relationship, and race at the
      margins. DISCUSSION/CONCLUSIONS: Whiteness obscured the participants'
      understanding and teaching of race; White nursing faculty were not well prepared
      to teach about race and racism; learning about these topics occurs best over time
      and through personal relationships. IMPLICATIONS: Faculty development regarding
      race and racism is needed to facilitate student, curricular, and institutional
      change.

PMID- 24682321
TI  - Japanese men's success in altered fatherhood role in a foreign country.
AB  - This study explores the meaning of the lived experience of childbirth and
      parenting of Japanese men who became fathers in a foreign country. Japanese men
      have been raised to maintain very strict gender roles, excluding them from
      sharing with their wives the experience of childbirth and the day-to-day
      parenting of young children. The study employed a descriptive phenomenological
      approach with in-depth interviews. Participants included nine Japanese men born
      and raised in Japan who were living in Honolulu. Three theme categories emerged
      from the data: "making active efforts in preparation for childbirth in a foreign
      country"; "challenges in pregnancy, childbirth, child care, and as husbands or
      partners"; and "challenges in transition to parenthood." Japanese men
      successfully altered their transitional and authoritarian gender role to a family
      orientated social structure, under the influence of Western values, when living
      in foreign country. By spending more time with their new family, they
      acknowledged the processes of becoming a father. The ability to adapt their
      expectations of fatherhood in line with Western values was enhanced by the
      support of coworkers, their mature age, rich educational background, and the
      personal financial resources of the male participants in the study. 

PMID- 24682322
TI  - The use of mouse models of breast cancer and quantitative image analysis to
      evaluate hormone receptor antigenicity after microwave-assisted formalin
      fixation.
AB  - Microwave methods of fixation can dramatically shorten fixation times while
      preserving tissue structure; however, it remains unclear if adequate tissue
      antigenicity is preserved. To assess and validate antigenicity, robust
      quantitative methods and animal disease models are needed. We used two mouse
      mammary models of human breast cancer to evaluate microwave-assisted and standard
      24-hr formalin fixation. The mouse models expressed four antigens prognostic for
      breast cancer outcome: estrogen receptor, progesterone receptor, Ki67, and human
      epidermal growth factor receptor 2. Using pathologist evaluation and novel
      methods of quantitative image analysis, we measured and compared the quality of
      antigen preservation, percentage of positive cells, and line plots of cell
      intensity. Visual evaluations by pathologists established that the amounts and
      patterns of staining were similar in tissues fixed by the different methods. The
      results of the quantitative image analysis provided a fine-grained evaluation,
      demonstrating that tissue antigenicity is preserved in tissues fixed using
      microwave methods. Evaluation of the results demonstrated that a 1-hr, 150-W
      fixation is better than a 45-min, 150-W fixation followed by a 15-min, 650-W
      fixation. The results demonstrated that microwave-assisted formalin fixation can
      standardize fixation times to 1 hr and produce immunohistochemistry that is in
      every way commensurate with longer conventional fixation methods. 

PMID- 24682323
TI  - Lowering GTP level increases survival of amino acid starvation but slows growth
      rate for Bacillus subtilis cells lacking (p)ppGpp.
AB  - Bacterial cells sense external nutrient availability to regulate macromolecular
      synthesis and consequently their growth. In the Gram-positive bacterium Bacillus
      subtilis, the starvation-inducible nucleotide (p)ppGpp negatively regulates GTP
      levels, both to resist nutritional stress and to maintain GTP homeostasis during
      growth. Here, we quantitatively investigated the relationship between GTP level,
      survival of amino acid starvation, and growth rate when GTP synthesis is
      uncoupled from its major homeostatic regulator, (p)ppGpp. We analyzed growth and
      nucleotide levels in cells that lack (p)ppGpp and found that their survival of
      treatment with a nonfunctional amino acid analog negatively correlates with both
      growth rate and GTP level. Manipulation of GTP levels modulates the exponential
      growth rate of these cells in a positive dose-dependent manner, such that
      increasing the GTP level increases growth rate. However, accumulation of GTP
      levels above a threshold inhibits growth, suggesting a toxic effect. Strikingly,
      adenine counteracts GTP stress by preventing GTP accumulation in cells lacking
      (p)ppGpp. Our results emphasize the importance of maintaining appropriate levels
      of GTP to maximize growth: cells can survive amino acid starvation by decreasing
      GTP level, which comes at a cost to growth, while (p)ppGpp enables rapid
      adjustment to nutritional stress by adjusting GTP level, thus maximizing fitness.

PMID- 24682325
TI  - Asymmetric constriction of dividing Escherichia coli cells induced by expression
      of a fusion between two min proteins.
AB  - The Min system, consisting of MinC, MinD, and MinE, plays an important role in
      localizing the Escherichia coli cell division machinery to midcell by preventing
      FtsZ ring (Z ring) formation at cell poles. MinC has two domains, MinCn and
      MinCc, which both bind to FtsZ and act synergistically to inhibit FtsZ
      polymerization. Binary fission of E. coli usually proceeds symmetrically, with
      daughter cells at roughly 180 degrees  to each other. In contrast, we discovered
      that overproduction of an artificial MinCc-MinD fusion protein in the absence of
      other Min proteins induced frequent and dramatic jackknife-like bending of cells
      at division septa, with cell constriction predominantly on the outside of the
      bend. Mutations in the fusion known to disrupt MinCc-FtsZ, MinCc-MinD, or MinD
      membrane interactions largely suppressed bending division. Imaging of FtsZ-green
      fluorescent protein (GFP) showed no obvious asymmetric localization of FtsZ
      during MinCc-MinD overproduction, suggesting that a downstream activity of the Z
      ring was inhibited asymmetrically. Consistent with this, MinCc-MinD fusions
      localized predominantly to segments of the Z ring at the inside of developing
      cell bends, while FtsA (but not ZipA) tended to localize to the outside. As FtsA
      is required for ring constriction, we propose that this asymmetric localization
      pattern blocks constriction of the inside of the septal ring while permitting
      continued constriction of the outside portion. 

PMID- 24682324
TI  - Evolution to a chronic disease niche correlates with increased sensitivity to
      tryptophan availability for the obligate intracellular bacterium Chlamydia
      pneumoniae.
AB  - The chlamydiae are obligate intracellular parasites that have evolved specific
      interactions with their various hosts and host cell types to ensure their
      successful survival and consequential pathogenesis. The species Chlamydia
      pneumoniae is ubiquitous, with serological studies showing that most humans are
      infected at some stage in their lifetime. While most human infections are
      asymptomatic, C. pneumoniae can cause more-severe respiratory disease and
      pneumonia and has been linked to chronic diseases such as asthma,
      atherosclerosis, and even Alzheimer's disease. The widely dispersed animal
      adapted C. pneumoniae strains cause an equally wide range of diseases in their
      hosts. It is emerging that the ability of C. pneumoniae to survive inside its
      target cells, including evasion of the host's immune attack mechanisms, is linked
      to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint
      compounds in this host-parasite battle. Interestingly, the animal strains of C.
      pneumoniae have a slightly larger genome, enabling them to cope better with
      metabolite restrictions. It therefore appears that as the evolutionarily more
      ancient animal strains have evolved to infect humans, they have selectively
      become more "susceptible" to the levels of key metabolites, such as tryptophan.
      While this might initially appear to be a weakness, it allows these human C.
      pneumoniae strains to exquisitely sense host immune attack and respond by rapidly
      reverting to a persistent phase. During persistence, they reduce their metabolic
      levels, halting progression of their developmental cycle, waiting until the
      hostile external conditions have passed before they reemerge. 

PMID- 24682326
TI  - Phylogeny poorly predicts the utility of a challenging horizontally transferred
      gene in Methylobacterium strains.
AB  - Horizontal gene transfer plays a crucial role in microbial evolution. While much
      is known about the mechanisms that determine whether physical DNA can be
      transferred into a new host, the factors determining the utility of the
      transferred genes are less clear. We have explored this issue using
      dichloromethane consumption in Methylobacterium strains. Methylobacterium
      extorquens DM4 expresses a dichloromethane dehalogenase (DcmA) that has been
      acquired through horizontal gene transfer and allows the strain to grow on
      dichloromethane as the sole carbon and energy source. We transferred the dcmA
      gene into six Methylobacterium strains that include both close and distant
      evolutionary relatives. The transconjugants varied in their ability to grow on
      dichloromethane, but their fitness on dichloromethane did not correlate with the
      phylogeny of the parental strains or with any single tested physiological factor.
      This work highlights an important limiting factor in horizontal gene transfer,
      namely, the capacity of the recipient strain to accommodate the stress and
      metabolic disruption resulting from the acquisition of a new enzyme or pathway.
      Understanding these limitations may help to rationalize historical examples of
      horizontal transfer and aid deliberate genetic transfers in biotechnology for
      metabolic engineering. 

PMID- 24682327
TI  - Function of the SpoVAEa and SpoVAF proteins of Bacillus subtilis spores.
AB  - The Bacillus subtilis spoVAEa and spoVAF genes are expressed in developing spores
      as members of the spoVA operon, which encodes proteins essential for the uptake
      and release of dipicolinic acid (DPA) during spore formation and germination.
      SpoVAF is likely an integral inner spore membrane protein and exhibits sequence
      identity to A subunits of the spore's nutrient germinant receptors (GRs), while
      SpoVAEa is a soluble protein with no obvious signals to allow its passage across
      a membrane. However, like SpoVAD, SpoVAEa is present on the outer surface of the
      spore's inner membrane, as SpoVAEa was accessible to an external biotinylation
      agent in spores and SpoVAEa disappeared in parallel with SpoVAD during proteinase
      K treatment of germinated spores. SpoVAEa and SpoVAD were also distributed
      similarly in fractions of disrupted dormant spores. Unlike spoVAD, spoVAEa is
      absent from the genomes of some spore-forming members of the Bacillales and
      Clostridiales orders, although SpoVAEa's amino acid sequence is conserved in
      species containing spoVAEa. B. subtilis strains lacking SpoVAF or SpoVAEa and
      SpoVAF sporulated normally, and the spores had normal DPA levels. Spores lacking
      SpoVAF or SpoVAEa and SpoVAF also germinated normally with non-GR-dependent
      germinants but more slowly than wild-type spores with GR-dependent germinants,
      and this germination defect was complemented by ectopic expression of the missing
      proteins. 

PMID- 24682328
TI  - Common requirement for the relaxosome of plasmid R1 in multiple activities of the
      conjugative type IV secretion system.
AB  - Macromolecular transport by bacterial type IV secretion systems involves
      regulated uptake of (nucleo)protein complexes by the cell envelope-spanning
      transport channel. A coupling protein receptor is believed to recognize the
      specific proteins destined for transfer, but the steps initiating their
      translocation remain unknown. Here, we investigate the contribution of a complex
      of transfer initiation proteins, the relaxosome, of plasmid R1 to translocation
      of competing transferable substrates from mobilizable plasmids ColE1 and CloDF13
      or the bacteriophage R17. We found that not only does the R1 translocation
      machinery engage the R1 relaxosome during conjugative self-transfer and during
      infection by R17 phage but it is also activated by its cognate relaxosome to
      mediate the export of an alternative plasmid. Transporter activity was optimized
      by the R1 relaxosome even when this complex itself could not be transferred,
      i.e., when the N-terminal activation domain (amino acids 1 to 992 [N1-992]) of
      TraI was present without the C-terminal conjugative helicase domain. We propose
      that the functional dependence of the transfer machinery on the R1 relaxosome for
      initiating translocation ensures that dissemination of heterologous plasmids does
      not occur at the expense of self-transfer. 

PMID- 24682329
TI  - Streptococcus mutans NADH oxidase lies at the intersection of overlapping
      regulons controlled by oxygen and NAD+ levels.
AB  - NADH oxidase (Nox, encoded by nox) is a flavin-containing enzyme used by the oral
      pathogen Streptococcus mutans to reduce diatomic oxygen to water while oxidizing
      NADH to NAD(+). The critical nature of Nox is 2-fold: it serves to regenerate
      NAD(+), a carbon cycle metabolite, and to reduce intracellular oxygen, preventing
      formation of destructive reactive oxygen species (ROS). As oxygen and NAD(+) have
      been shown to modulate the activity of the global transcription factors Spx and
      Rex, respectively, Nox is potentially poised at a critical junction of two stress
      regulons. In this study, microarray data showed that either addition of oxygen or
      loss of nox resulted in altered expression of genes involved in energy metabolism
      and transport and the upregulation of genes encoding ROS-metabolizing enzymes.
      Loss of nox also resulted in upregulation of several genes encoding transcription
      factors and signaling molecules, including the redox-sensing regulator gene rex.
      Characterization of the nox promoter revealed that nox was regulated by oxygen,
      through SpxA, and by Rex. These data suggest a regulatory loop in which the roles
      of nox in reduction of oxygen and regeneration of NAD(+) affect the activity
      levels of Spx and Rex, respectively, and their regulons, which control several
      genes, including nox, crucial to growth of S. mutans under conditions of
      oxidative stress. 

PMID- 24682330
TI  - Heterologous expression of Bartonella adhesin A in Escherichia coli by exchange
      of trimeric autotransporter adhesin domains results in enhanced adhesion
      properties and a pathogenic phenotype.
AB  - Human-pathogenic Bartonella henselae causes cat scratch disease and
      vasculoproliferative disorders. An important pathogenicity factor of B. henselae
      is the trimeric autotransporter adhesin (TAA) Bartonella adhesin A (BadA), which
      is modularly constructed, consisting of a head, a long and repetitive neck-stalk
      module, and a membrane anchor. BadA is involved in bacterial autoagglutination,
      binding to extracellular matrix proteins and host cells, and in proangiogenic
      reprogramming. The slow growth of B. henselae and limited tools for genetic
      manipulation are obstacles for detailed examination of BadA and its domains.
      Here, we established a recombinant expression system for BadA mutants in
      Escherichia coli allowing functional analysis of particular BadA domains. Using a
      BadA mutant lacking 21 neck-stalk repeats (BadA HN23), the BadA HN23 signal
      sequence was exchanged with that of E. coli OmpA, and the BadA membrane anchor
      was additionally replaced with that of Yersinia adhesin A (YadA). Constructs were
      cloned in E. coli, and hybrid protein expression was detected by immunoblotting,
      fluorescence microscopy, and flow cytometry. Functional analysis revealed that
      BadA hybrid proteins mediate autoagglutination and binding to collagen and
      endothelial cells. In vivo, expression of this BadA construct correlated with
      higher pathogenicity of E. coli in a Galleria mellonella infection model. 

PMID- 24682331
TI  - Demographic stochasticity and evolution of dispersion I. Spatially homogeneous
      environments.
AB  - The selection of dispersion is a classical problem in ecology and evolutionary
      biology. Deterministic dynamical models of two competing species differing only
      in their passive dispersal rates suggest that the lower mobility species has a
      competitive advantage in inhomogeneous environments, and that dispersion is a
      neutral characteristic in homogeneous environments. Here we consider models
      including local population fluctuations due to both individual movements and
      random birth and death events to investigate the effect of demographic
      stochasticity on the competition between species with different dispersal rates.
      In this paper, the first of two, we focus on homogeneous environments where
      deterministic models predict degenerate dynamics in the sense that there are many
      (marginally) stable equilibria with the species' coexistence ratio depending only
      on initial data. When demographic stochasticity is included the situation
      changes. A novel large carrying capacity ([Formula: see text]) asymptotic
      analysis, confirmed by direct numerical simulations, shows that a preference for
      faster dispersers emerges on a precisely defined [Formula: see text] time scale.
      We conclude that while there is no evolutionarily stable rate for competitors to
      choose in these models, the selection mechanism quantified here is the essential
      counterbalance in spatially inhomogeneous models including demographic
      fluctuations which do display an evolutionarily stable dispersal rate. 

PMID- 24682332
TI  - Modeling analysis of the lymphocytopoiesis dynamics in chronically irradiated
      residents of Techa riverside villages.
AB  - A biologically motivated dynamical model of the lymphocytopoietic system in
      irradiated humans is applied here to analyze the data obtained under
      hematological examinations of residents of Techa riverside villages. Those people
      were exposed to chronic irradiation with varying dose rates, due to the
      radioactive contamination of the river basin by the Mayak Production Association.
      Modeling studies revealed the relationship between the dynamics of the
      lymphocytopoietic system in the examined individuals and the variation of dose
      rate over the considered period of time. It is found that the developed model is
      capable of reproducing the decreased level of blood lymphocyte concentration
      observed during the period of maximum radiation exposure, the recovery processes
      in the system observed during the period of decreasing dose rate, as well as the
      enhanced mitotic activity of bone marrow precursor cells in this hematopoietic
      lineage observed during the entire period under consideration. Mechanisms of
      these effects of chronic irradiation on the human lymphocytopoietic system are
      elucidated based on the applied model. The results obtained demonstrate the
      efficiency of the developed model in the analysis, investigation, and prediction
      of effects of chronic irradiation with varying dose rate on the human
      lymphocytopoietic system. In particular, the developed model can be used for
      predicting any radiation injury of this vital system in people exposed to chronic
      irradiation due to environmental radiological events, such as anthropogenic
      radiation accidents or radiological terroristic attacks. 

PMID- 24682333
TI  - Oral perceptual discrimination of viscosity differences for non-newtonian liquids
      in the nectar- and honey-thick ranges.
AB  - Thickened liquids are frequently used in the management of oropharyngeal
      dysphagia. Previous studies suggest that compression of a liquid bolus between
      the tongue and the palate in the oral phase of swallowing serves a sensory
      function, enabling the tuning of motor behavior to match the viscosity of the
      bolus. However, the field lacks information regarding healthy oral sensory
      discrimination ability for small differences in liquid viscosity. We undertook to
      measure oral viscosity discrimination ability for five non-Newtonian xanthan gum
      thickened liquids in the nectar- and honey-thick range. Xanthan gum concentration
      ranged from 0.5 to 0.87 % and increased by an average of 0.1 % between stimuli in
      the array. This translated to an average apparent viscosity increase of 0.2-fold
      between adjacent stimuli at 50 reciprocal seconds (/s). A triangle test paradigm
      was used to study stimulus discrimination in 78 healthy adults in two, sex
      balanced age cohorts. Participants were provided 5-ml samples of liquids in sets
      of three; one liquid differed in xanthan gum concentration from the other two.
      Participants were required to sample the liquid orally and indicate which sample
      was perceived to have a different viscosity. A protocol of 20 sets (60 samples)
      allowed calculation of the minimum difference in xanthan gum concentration
      detected accurately. On average, participants were able to accurately detect a
      0.38-fold increase in xanthan-gum concentration, translating to a 0.67-fold
      increase in apparent viscosity at 50/s. The data did not suggest the existence of
      a nonlinear point boundary in apparent viscosity within the range tested. No
      differences in viscosity discrimination were found between age cohorts or as a
      function of sex. The data suggest that for xanthan gum-thickened liquids, there
      may be several increments of detectably different viscosity within the ranges
      currently proposed for nectar- and honey-thick liquids. If physiological or
      functional differences in swallowing can be demonstrated for these smaller
      increments of detectably different viscosity, more narrowly defined categories of
      thickened liquids for dysphagia management will be warranted.

PMID- 24682335
TI  - First UK prosecution for female genital mutilation raises concerns among doctors.

PMID- 24682334
TI  - Left atrial enlargement and risk of ischemic stroke in elderly treated
      hypertensive patients.
AB  - BACKGROUND: The independent prognostic significance of left atrial enlargement is
      not yet completely clear. We investigated the association between left atrial
      enlargement and risk of ischemic stroke in elderly treated hypertensive patients.
      METHODS: The occurrence of ischemic stroke was evaluated in 1,191 elderly treated
      hypertensive patients (age range = 60-90 years). Left atrium diameter (cm) was
      indexed by body surface area (m(2)) and subjects were divided into those with
      normal or enlarged (>=2.4cm/m(2)) left atrium. RESULTS: During the follow-up
      (9.1+/-4.9 years; range = 0.4-20 years), 139 ischemic strokes occurred. The event
      rate per 100 patient-years was 1.28. There were 86 strokes in patients with
      normal (= 928) left atrium and 53 strokes in patients with enlarged (= 263) left
      atrium, respectively. Stroke-free survival curves were significantly different
      between the groups (P < 0.01). After adjustment for various covariables,
      including clinical variables, left ventricular hypertrophy, and ambulatory blood
      pressure parameters, Cox regression analysis showed that left atrial enlargement
      was significantly associated with increased risk of ischemic stroke (hazard ratio
      = 1.54; 95% confidence interval = 1.05-2.27; P = 0.03). CONCLUSIONS: In elderly
      treated hypertensive patients, left atrial enlargement is an independent
      predictor of ischemic stroke.

PMID- 24682336
TI  - Optimization of surgical ventricular restoration by in-silico simulations.
AB  - OBJECTIVE: A hypothesis on left ventricular aneurysms states that there is better
      preservation of contractile myocardium when the aneurysm geometry is rectangular
      as opposed to circular. Pre-surgical planning of surgical ventricular restoration
      was performed on the basis of this hypothesis. METHODS: The intraventricular
      patch used to exclude scarred or aneurysmal myocardium remains akinetic, hence it
      was used to define aneurysm geometry as circular or rectangular. Hausdorff
      distance analysis was carried out by mathematical computational methods on the
      baseline cardiac magnetic resonance images of 5 patients. RESULTS: The mean
      Hausdorff distance for the full range of frequencies was significantly greater
      after endoventricular linear patch plasty (0.474 +/- 0.190 vs. 0.722 +/- 0.221
      mm, p = 0.047), whereas after endoventricular circular patch plasty, the
      difference was not significant (0.474 +/- 0.190 vs. 0.594 +/- 0.193, p = 0.175).
      The mean Hausdorff distance <0.5 mm was also significantly greater after
      endoventricular linear patch plasty than after endoventricular circular patch
      plasty: 0.258 +/- 0.03 mm at baseline vs. 0.40 +/- 0.16 mm after linear patch
      plasty (p = 0.039) and 0.258 +/- 0.03 vs. 0.32 +/- 0.10 mm (p = 0.130) after
      circular patch plasty. CONCLUSIONS: In-silico technology using the Hausdorff
      distance enables pre-surgical planning and optimization of the technique for
      surgical ventricular restoration.

PMID- 24682337
TI  - Tricuspid annuloplasty with the MC3 ring and septal plication technique.
AB  - BACKGROUND: Functional tricuspid regurgitation is caused by annular dilation
      mainly in the posterior annulus. However, ring annuloplasty does not always
      prevent the recurrence of tricuspid regurgitation due to dilation of the septal
      annulus. We developed a septal plication technique with a 3-dimensional MC3 ring.
      METHODS: Between 2006 and 2011, 76 patients (male/female 30/46; mean age 68 +/-
      11 years) with functional tricuspid regurgitation received tricuspid ring
      annuloplasty. After placement of the annular sutures, the 3 commissural ring
      portions were fixed on the equivalent commissures to plicate the anterior and
      posterior annulus. The end of the septal ring portion was fixed at the optimal
      annular position to obtain minimal tricuspid regurgitation. All patients were
      followed-up for a mean of 47 +/- 18 months; the longest duration was 79 months.
      RESULTS: Although there was no operative death, one patient died of sepsis during
      hospitalization (hospital mortality 1.3%). After implantation of the MC3 ring
      (mean size 31.0 +/- 3.3 mm), additional edge-to-edge sutures were required for
      minor leakage in 5 (7%) patients. The degree of tricuspid regurgitation was
      significantly reduced at discharge (0.5 +/- 0.6) and midterm (0.6 +/- 0.6)
      compared to 2.5 +/- 0.7 before the operation (p < 0.0001). CONCLUSIONS: The
      surgical durability of the MC3 ring was satisfactory at early and midterm follow
      up, suggesting that correct plication of the septal annulus is effective for
      tricuspid ring annuloplasty with a 3-dimensional MC3 ring.

PMID- 24682338
TI  - Unique presentation of a primary pleomorphic sarcoma of the left atrium.
AB  - This report describes an extremely rare cause of a common presentation. A 59-year
      old man who presented with symptoms of progressive cardiac failure, was
      demonstrated to have a large left intraatrial mass on computed tomography
      pulmonary angiography and an echocardiogram. He proceeded to urgent surgery under
      cardiopulmonary bypass. Histology of the resected mass diagnosed primary
      pleomorphic sarcoma of the left atrium. This exceedingly rare malignancy has a
      poor prognosis and often presents with nonspecific symptoms. Echocardiography
      remains vital in diagnosis, and treatment is primarily surgical excision, with
      some reports of adjuvant chemotherapy. 

PMID- 24682339
TI  - Vibrio parahaemolyticus and its specific bacteriophages as an indicator in
      cockles (Anadara granosa) for the risk of V. parahaemolyticus infection in
      Southern Thailand.
AB  - Correlation between the numbers of Vibrio parahaemolyticus and its specific
      bacteriophages in cockles was investigated from June 2009 to May 2010 in Hat Yai,
      Songkhla, Thailand. Cockles obtained monthly from a local market were sampled to
      determine the numbers of V. parahaemolyticus and bacteriophages that could form
      plaques on ten strains of pandemic and nonpandemic V. parahaemolyticus. In
      addition, V. parahaemolyticus isolates from clinical samples from Hat Yai
      hospital over the same period were investigated. All 139 cockles sampled were
      positive for V. parahaemolyticus. However, only 76 of them were positive for
      bacteriophages. During the testing period, the number of bacteriophages was not
      significantly correlated with the incidence of V. parahaemolyticus-infected
      patients, but the numbers of V. parahaemolyticus isolates from the cockle samples
      were closely related to the number of infected patients. The bacteriophages
      isolated from V. parahaemolyticus also infected Vibrio alginolyticus and Vibrio
      mimicus, suggesting that the broad host range of phages may be a factor of
      providing the possibility of their participation in the processes of genetic
      exchange between V. parahaemolyticus and closely related Vibrio spp. In
      conclusion, this study indicated that the number of V. parahaemolyticus in
      cockles may be a useful tool for predicting the relative risk of infection by V.
      parahaemolyticus in this area of Thailand. 

PMID- 24682340
TI  - Culture-dependent and culture-independent analysis of hydrocarbonoclastic
      microorganisms indigenous to hypersaline environments in Kuwait.
AB  - The halophilic, hydrocarbonoclastic bacteria and archaea inhabiting two
      hypersaline coastal areas in Kuwait, one in the north and the other in the south,
      were counted and characterized. Environmental parameters in both areas were
      similar, with the exception of the soil organic carbon content, which was in the
      north higher than in the south. The hydrocarbonoclastic bacterial and
      haloarchaeal numbers and identities as analyzed using nutrient media of various
      salinities were similar in soil and pond water samples from both areas. The
      bacterial species recorded by this culture-dependent method belonged to the
      genera Halomonas, Chromohalobacter, Marinobacter, Exiguobacterium,
      Stenotrophomonas, Pseudomonas, Salinivibrio, and Bacillus. The haloarchaeal
      species belonged to the genera Haloferax and Halobacterium. When analyzed by
      fingerprinting of their amplified genomic DNA followed by sequencing of the
      electrophoresis-resolved bands, the same environmental samples revealed a
      different microbial composition. Bacterial phylotypes recorded by this culture
      independent method were affiliated with the genera Ochrobactrum,
      Stenotrophomonas, Rhodococcus, and "Halomicrobium," whereas the archaeal
      phylotypes were affiliated with Halorussus, Halomicrobium, and Halorientalis. The
      observed diversity and composition similarity of the hydrocarbonocalastic
      microflora in both hypersaline areas suggest an effective potential for oil
      mineralization therein. This potential has been confirmed experimentally. 

PMID- 24682342
TI  - Pyrosequencing reveals diverse microbial community associated with the zoanthid
      Palythoa australiae from the South China Sea.
AB  - Diverse sessile organisms inhabit the coral reef ecosystems, including corals,
      sponges, and sea anemones. In the past decades, scleractinian corals (Cnidaria,
      Anthozoa, Scleractinia) and their associated microorganisms have attracted much
      attention. Zoanthids (Cnidaria, Anthozoa, Zoanthidea) are commonly found in coral
      reefs. However, little is known about the community structure of zoanthid
      associated microbiota. In this study, the microbial community associated with the
      zoanthid Palythoa australiae in the South China Sea was investigated by 454
      pyrosequencing. As a result, 2,353 bacterial, 583 archaeal, and 36 eukaryotic
      microbial ribotypes were detected, respectively. A total of 22 bacterial phyla
      (16 formally described phyla and six candidate phyla) were recovered.
      Proteobacteria was the most abundant group, followed by Chloroflexi and
      Actinobacteria. High-abundance Rhizobiales and diverse Chloroflexi were observed
      in the bacterial community. The archaeal population was composed of Crenarchaeota
      and Euryarchaeota, with Marine Group I as the dominant lineage. In particular,
      Candidatus Nitrosopumilus dominated the archaeal community. Besides bacteria and
      archaea, the zoanthid harbored eukaryotic microorganisms including fungi and
      algae though their diversity was very low. This study provided the first insights
      into the microbial community associated with P. australiae by 454 pyrosequencing,
      consequently laid a basis for the understanding of the association of P.
      australiae-microbes symbioses. 

PMID- 24682341
TI  - Initial copper stress strengthens the resistance of soil microorganisms to a
      subsequent copper stress.
AB  - To improve the prediction of essential ecosystem functioning under future
      environmental disturbances, it is of significance to identify responses of soil
      microorganisms to environmental stresses. In this study, we collected polluted
      soil samples from field plots with eight copper levels ranging from 0 to 3,200 mg
      Cu kg(-1) soil. Then, the soils with 0 and 3,200 mg Cu kg(-1) were selected to
      construct a microcosm experiment. Four treatments were set up including Cu0-C and
      Cu3200-C without further Cu addition, and Cu0-A and Cu3200-A with addition of
      57.5 mg Cu kg(-1) soil. We measured substrate-induced respiration (SIR) and
      potential nitrification rate (PNR). Furthermore, the abundance of bacterial,
      archaeal 16S rRNA genes, ammonia-oxidizing bacteria and archaea amoA genes were
      determined through quantitative PCR. The soil microbial communities were
      investigated by terminal restriction fragment length polymorphism (T-RFLP). For
      the field samples, the SIR and PNR as well as the abundance of soil
      microorganisms varied significantly between eight copper levels. Soil microbial
      communities highly differed between the low and high copper stress. In the
      microcosm experiment, the PNR and SIR both recovered while the abundance of soil
      microorganisms varied irregularly during the 90-day incubation. The differences
      of microbial communities measured by pairwise Bray-Curtis dissimilarities between
      Cu0-A and Cu0-C on day 0 were significantly higher after subsequent stress than
      before. However, the differences of microbial communities between Cu3200-A and
      Cu3200-C on day 0 changed little between after subsequent stress and before.
      Therefore, initial copper stress could increase the resistance of soil
      microorganisms to subsequent copper stress.

PMID- 24682346
TI  - Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary
      left ventricular assist devices.
AB  - BACKGROUND: Allogeneic mesenchymal precursor cells (MPCs) injected during left
      ventricular assist device (LVAD) implantation may contribute to myocardial
      recovery. This trial explores the safety and efficacy of this strategy. METHODS
      AND RESULTS: In this multicenter, double-blind, sham-procedure controlled trial,
      30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs
      or medium during LVAD implantation. The primary safety end point was incidence of
      infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction,
      and immune sensitization (90 days after randomization). Key efficacy end points
      were functional status and ventricular function while temporarily weaned from
      LVAD support (90 days after randomization). Patients were followed up until
      transplant or 12 months after randomization, whichever came first. Mean age was
      57.4 (+/-13.6) years, mean left ventricular ejection fraction was 18.1%, and
      66.7% were destination therapy LVADs. No safety events were observed. Successful
      temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at
      90 days (P=0.24); the posterior probability that MPCs increased the likelihood of
      successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control
      patients, and none occurred in MPC patients. Mean left ventricular ejection
      fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56).
      At 12 months, 30% of MPC patients and 40% of control patients were successfully
      temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC
      patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control
      patients and resolved by 12 months. CONCLUSIONS: In this preliminary trial,
      administration of MPCs appeared to be safe, and there was a potential signal of
      efficacy. Future studies will evaluate the potential for higher or additional
      doses to enhance the ability to wean LVAD recipients off support. CLINICAL TRIAL
      REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.

PMID- 24682348
TI  - 2014 AHA/ACC/HRS guideline for the management of patients with atrial
      fibrillation: executive summary: a report of the American College of
      Cardiology/American Heart Association Task Force on practice guidelines and the
      Heart Rhythm Society.

PMID- 24682349
TI  - ACC/AHA/SCAI 2014 health policy statement on structured reporting for the cardiac
      catheterization laboratory: a report of the American College of Cardiology
      Clinical Quality Committee.

PMID- 24682350
TI  - Protective effects of L-alpha-glycerylphosphorylcholine on ischaemia-reperfusion
      induced inflammatory reactions.
AB  - PURPOSE: Choline-containing dietary phospholipids, including phosphatidylcholine
      (PC), may function as anti-inflammatory substances, but the mechanism remains
      largely unknown. We investigated the effects of L-alpha-glycerylphosphorylcholine
      (GPC), a deacylated PC derivative, in a rodent model of small intestinal
      ischaemia-reperfusion (IR) injury. METHODS: Anaesthetized Sprague-Dawley rats
      were divided into control, mesenteric IR (45 min mesenteric artery occlusion,
      followed by 180 min reperfusion), IR with GPC pretreatment (16.56 mg kg-1 GPC
      i.v., 5 min prior to ischaemia) or IR with GPC post-treatment (16.56 mg kg-1 GPC
      i.v., 5 min prior to reperfusion) groups. Macrohaemodynamics and
      microhaemodynamic parameters were measured; intestinal inflammatory markers
      (xanthine oxidoreductase activity, superoxide and nitrotyrosine levels) and liver
      ATP contents were determined. RESULTS: The IR challenge reduced the intestinal
      intramural red blood cell velocity, increased the mesenteric vascular resistance,
      the tissue xanthine oxidoreductase activity, the superoxide production, and the
      nitrotyrosine levels, and the ATP content of the liver was decreased. Exogenous
      GPC attenuated the macro- and microcirculatory dysfunction and provided
      significant protection against the radical production resulting from the IR
      stress. The GPC pretreatment alleviated the hepatic ATP depletion, the reductions
      in the mean arterial pressure and superior mesenteric artery flow, and similarly
      to the post-treatments with GPC, also decreased the xanthine oxidoreductase
      activity, the intestinal superoxide production, the nitrotyrosine level, and
      normalized the microcirculatory dysfunction. CONCLUSIONS: These data demonstrate
      the effectiveness of GPC therapies and provide indirect evidence that the anti
      inflammatory effects of PC could be linked to a reaction involving the polar part
      of the molecule.

PMID- 24682352
TI  - Sexual Dimorphism in the Alterations of Cardiac Muscle Mitochondrial
      Bioenergetics Associated to the Ageing Process.
AB  - The incidence of cardiac disease is age and sex dependent, but the mechanisms
      governing these associations remain poorly understood. Mitochondria are the
      organelles in charge of producing energy for the cells, and their malfunction has
      been linked to cardiovascular disease and heart failure. Interestingly, heart
      mitochondrial content and functionality are also age and sex dependent. Here we
      investigated the combinatory effects of age and sex in mitochondrial
      bioenergetics that could help to understand their role on cardiac disease.
      Cardiac mitochondria from 6- and 24-month-old male and female Wistar rats were
      isolated, and the enzymatic activities of the oxidative-phosphorylative complexes
      I, III, and IV and ATPase, as well as the protein levels of complex IV, beta
      ATPase, and mitochondrial transcription factor A (TFAM), were measured.
      Furthermore, heart DNA content, citrate synthase activity, mitochondrial protein
      content, oxygen consumption, and H2O2 generation were also determined. Results
      showed a reduction in heart mitochondrial mass and functionality with age that
      correlated with increased H2O2 generation. Moreover, sex-dependent differences
      were found in several of these parameters. In particular, old females exhibited a
      significant loss of mitochondrial function and increased relative H2O2 production
      compared with their male counterparts. The results demonstrate a sex dimorphism
      in the age-associated defects on cardiac mitochondrial function. 

PMID- 24682351
TI  - Body mass index from age 15 years onwards and muscle mass, strength, and quality
      in early old age: findings from the MRC National Survey of Health and
      Development.
AB  - BACKGROUND: As more people live more of their lives obese, it is unclear what
      impact this will have on muscle mass, strength, and quality. We aimed to examine
      the associations of body mass index (BMI) from age 15 years onwards with low
      muscle mass, strength, and quality in early old age. METHODS: A total of 1,511
      men and women from a British birth cohort study with BMI measured at 15, 20, 26,
      36, 43, 53, and 60-64 years and dual-energy x-ray absorptiometry scans at 60-64
      years were included. Four binary outcomes identified those in the bottom sex
      specific 20% of (a) appendicular lean mass (ALM) index (kilogram per square
      meter), (b) ALM residuals (derived from sex-specific models in which ALM
      (kilogram) = beta0 + beta1 height [meter] + beta2 fat mass [kilogram]), (c) grip
      strength (kilogram), (d) muscle quality (grip strength [kilogram]/arm lean mass
      [kilogram]). Associations of BMI with each outcome were tested. RESULTS: Higher
      BMI from age 15 years was associated with lower odds of low ALM but higher odds
      of low muscle quality (per 1 SD increase in BMI at 36 years, odds ratio of low
      ALM residuals = 0.50 [95% CI: 0.43, 0.59], and muscle quality = 1.50 [1.29,
      1.75]). Greater gains in BMI were associated with lower odds of low ALM index but
      higher odds of low muscle quality. BMI was not associated with grip strength.
      CONCLUSIONS: Given increases in the global prevalence of obesity, cross-cohort
      comparisons of sarcopenia need to consider our findings that greater gains in BMI
      are associated with higher muscle mass but not with grip strength and therefore
      with lower muscle quality.

PMID- 24682353
TI  - Baicalein pretreatment confers cardioprotection against acute myocardial
      infarction by activating the endothelial nitric oxide synthase signaling pathway
      and inhibiting oxidative stress.
AB  - Baicalein, a flavonoid purified from the root of Scutellaria baicalensis Georgi,
      is well known for its anti-inflammatory and anti-oxidative properties. The
      present study aimed to evaluate the cardioprotective effect of baicalein in a rat
      model of acute myocardial infarction and investigate the potential molecular
      mechanisms of this effect. The acute myocardial infarction model was prepared by
      permanently occluding the left anterior descending artery. Baicalein and/or the
      endothelial nitric oxide synthase (eNOS) inhibitor L-NAME was injected prior to
      the induction of acute myocardial infarction. In the vehicle-treated group, acute
      myocardial infarction resulted in a markedly increased infarction size and
      elevated levels of plasma cardiac enzymes, including creatine kinase, the MB
      isoenzyme of creatine kinase, lactate dehydrogenase and cardiac troponin T,
      compared with those in the sham-surgery group. In the baicalein treatment group,
      the infarcted area and plasma levels of the cardiac enzymes were significantly
      decreased compared with those in the vehicle-treated group. In addition,
      pretreatment with baicalein potently increased the levels of eNOS protein and
      nitric oxide production in the infarcted rats. Furthermore, myocardial oxidative
      stress was attenuated by baicalein preconditioning following acute myocardial
      infarction. However, L-NAME inihibted the cardioprotective effects of baicalein.
      These data indicate that baicalein protects against acute myocardial infarction
      induced injury by activating eNOS signaling and inhibiting oxidative stress.

PMID- 24682354
TI  - Analysis of MRI signal changes in the adjacent pedicle of adolescent patients
      with fresh lumbar spondylolysis.
AB  - PURPOSE: The purpose of this study is to investigate a discrepancy between MRI
      and computed tomography (CT) findings in the spinal level distribution of
      spondylolysis. Recent advances in MRI have led to the early diagnosis of
      spondylolysis. Therefore, bony healing can be expected before the condition has a
      chance to worsen. In this study, we used MRI to examine the changes in spinal
      level signals in the pedicles adjacent to the pars interarticularis in
      adolescents with fresh lumbar spondylolysis. We then compared spinal level
      distribution of spondylolysis with that of previous results obtained by
      multidetector CT. METHODS: The study included 98 adolescent patients (31 women
      and 67 men; mean age, 13.6 years; age range, 9-18 years) with fresh lumbar
      spondylolysis who showed MRI signal changes in the adjacent pedicle. An MRI
      signal change was defined as a high signal change on fat-suppressed imaging.
      RESULTS: MRI signal changes were detected in 150 adjacent pedicles of 101
      vertebrae. Of these vertebrae, MRI signal changes in only 67 (66.3%) corresponded
      to L5, while changes in 34 (33.7%) corresponded to L3 or L4. In our follow-up
      study, the bone-healing rate with no vertebral defect was 100% at L3, 97.1% at
      L4, and 84.4% at L5. In addition, 11 of 34 (32.4%) vertebrae with signal changes
      at L3 or L4 occurred with L5 terminal-stage spondylolysis (no MRI signal change).
      CONCLUSION: MRI revealed a higher prevalence of L3 or L4 spondylolysis than
      observed with CT.

PMID- 24682356
TI  - Active self-correction and task-oriented exercises reduce spinal deformity and
      improve quality of life in subjects with mild adolescent idiopathic scoliosis.
      Results of a randomised controlled trial.
AB  - PURPOSE: To evaluate the effect of a programme of active self-correction and task
      oriented exercises on spinal deformities and health-related quality of life
      (HRQL) in patients with mild adolescent idiopathic scoliosis (AIS) (Cobb angle
      <25 degrees ). METHODS: This was a parallel-group, randomised, superiority
      controlled study in which 110 patients were randomly assigned to a rehabilitation
      programme consisting of active self-correction, task-oriented spinal exercises
      and education (experimental group, 55 subjects) or traditional spinal exercises
      (control group, 55 subjects). Before treatment, at the end of treatment (analysis
      at skeletal maturity), and 12 months later (follow-up), all of the patients
      underwent radiological deformity (Cobb angle), surface deformity (angle of trunk
      rotation) and HRQL evaluations (SRS-22 questionnaire). A linear mixed model for
      repeated measures was used for each outcome measure. RESULTS: There were main
      effects of time (p < 0.001), group (p < 0.001) and time by group interaction (p <
      0.001) on radiological deformity: training in the experimental group led to a
      significant improvement (decrease in Cobb angle of >5 degrees ), whereas the
      control group remained stable. Analysis of all of the secondary outcome measures
      revealed significant effects of time, group and time by group interaction in
      favour of the experimental group. CONCLUSIONS: The programme of active self
      correction and task-oriented exercises was superior to traditional exercises in
      reducing spinal deformities and enhancing the HRQL in patients with mild AIS. The
      effects lasted for at least 1 year after the intervention ended.

PMID- 24682355
TI  - Classification of sagittal imbalance based on spinal alignment and compensatory
      mechanisms.
AB  - INTRODUCTION: Sagittal balance is an independent predictor of clinical outcomes
      in spinal care. Surgical treatment is challenging and jeopardized by frequent
      complications. Guidelines for surgical treatment are currently not based on a
      classification of the disease. A comprehensive classification of sagittal balance
      based on regional deformities and compensatory mechanisms combined in deformity
      patterns is proposed. Though the sagittal shape of the spine can change due to
      degeneration or trauma, correlations between sagittal shape parameters and pelvic
      incidence (PI) have been described. Pelvic incidence is not changed by
      degeneration, thus representing a permanent source of information on the original
      sagittal shape of the spine. METHODS: One hundred and twenty-eight full-spine
      lateral standing radiographs of patients with different spinal conditions were
      evaluated and classified by one rater. One random subseries of 35 patients was
      evaluated by two raters for calculation of inter-rater agreement. Spinopelvic
      parameters were measured in all the radiographs. Internal validity of the
      classification system was evaluated comparing the values of regional sagittal
      parameters that distinguish one category from the others. RESULTS: Eight
      different patterns were identified regarding the site of the deformity and the
      presence of compensatory mechanisms: cervical, thoracic, thoracolumbar junction,
      lumbar, lower lumbar, global and pelvic kyphosis and normal sagittal alignment.
      Inter-rater agreement was almost perfect (kappa = 0.963). Statistically
      significant differences were found comparing the means of selected sagittal
      spinopelvic parameters that conceptually divide pairs or groups of categories: C2
      C7 SVA for cervical kyphosis vs all other patients, TK-PI mismatch for thoracic
      kyphosis vs all other patients, T11-L2 kyphosis for thoracolumbar kyphosis vs all
      other patients, global alignment (LL+TK-PI) and SVA for lumbar kyphosis vs global
      kyphosis and pelvic tilt for pelvic kyphosis vs lumbar, lower lumbar and global
      kyphosis. CONCLUSION: A comprehensive classification of sagittal imbalance is
      presented. This classification permits a better interpretation of the deformity
      and muscle forces acting on the spine, and helps surgical planning. Preliminary
      validation has been provided.

PMID- 24682358
TI  - Meningitis following spinal anaesthesia in an obstetric patient.
AB  - Meningitis following lumbar puncture and spinal anaesthesia is a rare but serious
      complication. A 19-year-old woman was administered spinal anaesthesia at another
      centre prior to a Caesarean section. The following day she experienced headaches.
      On the fourth day, she started vomiting and having convulsions, and became
      agitated. Meningitis was diagnosed based on a clinical examination and analysis
      of a lumbar puncture sample. After 21 days of treatment, she was discharged.
      Meningitis should be considered in the differential diagnosis of a patient
      presenting with headaches following spinal anaesthesia. The causes of meningitis
      following spinal anaesthesia are debated, and it is difficult to distinguish
      between aseptic and bacterial meningitis. It should be compulsory to wear a face
      mask while performing a dural puncture. 

PMID- 24682357
TI  - Vitamin D receptor variability and physical activity are jointly associated with
      low handgrip strength and osteoporosis in community-dwelling elderly people in
      Taiwan: the Taichung Community Health Study for Elders (TCHS-E).
AB  - We studied 472 elders to assess joint association of vitamin D receptor (VDR)
      variability and physical activity on low handgrip strength (LHS) and osteoporosis
      (OST). Our findings showed that higher risks of OST were associated with
      physically inactive elders with some specific VDR variations, highlighting the
      importance of promotion program for physical activity. INTRODUCTION: The aim of
      this study was to determine the joint association between VDR variability and
      physical activity on LHS and OST in community-dwelling elders. METHODS: Bone
      mineral density of the lumbar spine (LS), the femoral neck (FN), and the total
      hip were measured by dual-energy X-ray absorptiometry. Four single-nucleotide
      polymorphisms (SNPs) (rs7975232, rs1544410, rs2239185, and rs3782905) of the VDR
      gene were examined in 472 participants. RESULTS: Physical inactivity and each of
      the four SNPs were jointly associated with a significantly greater risk of LHS in
      people than that associated with each of the VDR SNPs or low physical activity
      alone. Physically inactive men with the AG or AA genotype of rs2239185 had a
      significantly greater risk of overall, LS, and FN OST than those of physically
      active men with the GG genotype [odds ratio (OR) 3.57, 95 % confidence interval
      (CI) 1.10-11.65; OR 4.74, 95 % CI 1.43-15.70; and OR 5.06, 95 % CI 1.08-23.71,
      respectively]. Similarly, physically inactive women with the CG or CC genotype of
      rs3782905 and the AG or AA genotype of rs1544410 had a significantly greater risk
      of FN OST than physically active women with the GG genotype (OR 5.33, 95 % CI
      1.23-23.06 and OR 5.36, 95 % CI 1.11-25.94, respectively). CONCLUSIONS: VDR
      polymorphisms and physical activity are jointly associated with LHS and OST in
      elders. Health care programs should promote physical activity among elders as a
      cost-effective way to prevent LHS and OST, especially in those who may be
      genetically predisposed.

PMID- 24682347
TI  - 2014 AHA/ACC/HRS guideline for the management of patients with atrial
      fibrillation: a report of the American College of Cardiology/American Heart
      Association Task Force on practice guidelines and the Heart Rhythm Society.

PMID- 24682359
TI  - Nocturnal journey of body and mind in Parkinson's disease: the manifestations,
      risk factors and their relationship to daytime symptoms. Evidence from the NIGHT
      PD study.
AB  - Nocturnal manifestations of Parkinson's disease (PD) are myriad, have diverse
      etiologies and include motor, sleep, urinary, and neuropsychiatric symptoms which
      are often associated with daytime somnolence. While most patients perceive these
      symptoms as troublesome, the recognition of nocturnal problems related to PD is
      still low in clinical practice. We conducted a survey using semi-structured
      interviews and self-rated questionnaires of 215 consecutive patients with PD
      enrolled in three centers in Thailand to determine the prevalence and risk
      factors of nocturnal disabilities and their relationship to daytime symptoms. We
      found that 96.6% of patients reported the presence of nocturnal symptoms as
      determined by the modified version of Parkinson's Disease Sleep Scale (MPDSS).
      Our survey indicated that the most frequent and distressing symptom was the
      interruption of sleep to pass urine (56.7%, 4.4 +/- 3.9). The severity of
      symptoms revealed in the MPDSS increased along with the disease duration (p <
      0.05) and Hoehn and Yahr stages (p = 0.01). There were similar to findings of the
      Nocturnal Akinesia Dystonia and Cramp Score (NADCS) where patients with advanced
      disease had significantly higher NADCS scores than early/moderate disease (p <
      0.001). There was a significant correlation of total MPDSS scores with the total
      scores of the 9-item Wearing-Off Questionnaire (WOQ-9); (r = -0.43, p < 0.05)
      [motor (r = -0.35, p < 0.05) and nonmotor subscores (r = -0.43, p < 0.05)]; total
      nonmotor symptoms (NMS) scores (r = -0.55, p < 0.05); Parkinson's Disease
      Questionnaire-8 Summary Index (PDQ-8 SI) (r = -0.52, p < 0.05); and the total
      NADCS (r = -0.35, p < 0.05). Multiple regression analysis identified PDQ-8 SI
      (beta = -0.27, p = 0.005) as the most significant predictor of nocturnal
      manifestations of PD, followed by the nonmotor subscore of WOQ (beta = -0.24, p =
      0.006), and the NMS item 20 (feeling light-headed, dizzy, or weak when standing
      from sitting or lying) (beta = -0.22, p = 0.003). Our study found that nocturnal
      symptoms of PD are very common and we suggest that good clinical practice should
      include a comprehensive review of nighttime manifestations, particularly for
      those patients who already experience "wearing-off" symptoms.

PMID- 24682360
TI  - The impact of the nocturnal disabilities of Parkinson's disease on caregivers'
      burden: implications for interventions.
AB  - Parkinson's disease (PD) imposes a burden on those who care for the person
      afflicted. The objective of this study was to assess and analyze the main
      determinants of caregivers' burden, especially the nocturnal manifestations of
      PD. This multi-center, national, cross-sectional study included 89 patient
      caregiver pairs. Caregiver self-assessments were performed with Hospital Anxiety
      and Depression Scale (HADS) and Zarit Caregiver Burden Interview (ZCBI). Patient
      self-assessments were performed with Modified Parkinson's Disease Sleep Scale
      (MPDSS), Nocturnal Akinesia Dystonia and Cramp Score (NADCS), HADS and
      Parkinson's Disease Quality of Life Questionnaire (PDQ-8). Most of the caregivers
      were employed women, and the majority had been permanently taking care of the
      patient for 6.8 +/- 5.4 years. The study found that the ZCBI mean score of the
      caregivers significantly worsened as patients became more dependent (HY: 4-5, p =
      0.036), and the mean ZCBI score of spousal caregivers (19.4; SD 15.5) was
      significantly higher than that of the offspring group (11.7; SD 7.9) (p = 0.008).
      Disease duration (r = 0.22), NADCS (r = 0.38), MPDSS (r = -0.36), PDQ-8 SI (r =
      0.39) and HADS (total, anxiety and depression) scores (r = 0.46-0.49), and HADS
      (total, anxiety and depression scores (r = 0.37-0.52), had significant negative
      effect on caregivers' burden. Moderate association was found on MPDSS item 14 (r
      = 0.38) and NADCS akinesia score (r = 0.37). Patients' anxiety, nocturnal
      akinesia and the feeling of tiredness and sleepiness upon awakening in the
      morning were independent predictors of caregivers' burden (adjusted R2 = 0.46).
      Based on these findings, treatment of early mood symptoms of the patients and
      caregivers at risk may be helpful for the effective management of PD and it is
      also important to have well-designed psycho-educational and multicomponent
      interventions in the community for caregivers of persons with PD.

PMID- 24682363
TI  - [Not Available].

PMID- 24682362
TI  - Groove-type recognition of chlamydiaceae-specific lipopolysaccharide antigen by a
      family of antibodies possessing an unusual variable heavy chain N-linked glycan.
AB  - The structure of the antigen binding fragment of mAb S25-26, determined to 1.95 A
      resolution in complex with the Chlamydiaceae family-specific trisaccharide
      antigen Kdo(2->8)Kdo(2->4)Kdo (Kdo = 3-deoxy-alpha-d-manno-oct-2-ulopyranosonic
      acid), displays a germ-line-coded paratope that differs significantly from
      previously characterized Chlamydiaceae-specific mAbs despite being raised against
      the identical immunogen. Unlike the terminal Kdo recognition pocket that promotes
      cross-reactivity in S25-2-type antibodies, S25-26 and the closely related S25-23
      utilize a groove composed of germ-line residues to recognize the entire
      trisaccharide antigen and so confer strict specificity. Interest in S25-23 was
      sparked by its rare high MUm affinity and strict specificity for the family
      specific trisaccharide antigen; however, only the related antibody S25-26 proved
      amenable to crystallization. The structures of three unliganded forms of S25-26
      have a labile complementary-determining region H3 adjacent to significant
      glycosylation of the variable heavy chain on asparagine 85 in Framework Region 3.
      Analysis of the glycan reveals a heterogeneous mixture with a common root
      structure that contains an unusually high number of terminal alphaGal-Gal
      moieties. One of the few reported structures of glycosylated mAbs containing
      these epitopes is the therapeutic antibody Cetuximab; however, unlike Cetuximab,
      one of the unliganded structures in S25-26 shows significant order in the glycan
      with appropriate electron density for nine residues. The elucidation of the three
      dimensional structure of an alphaGal-containing N-linked glycan on a mAb variable
      heavy chain has potential clinical interest, as it has been implicated in
      allergic response in patients receiving therapeutic antibodies. 

PMID- 24682372
TI  - Red meat consumption and stomach cancer risk: a meta-analysis.
AB  - PURPOSE: The association of red meat consumption with the risk of stomach cancer
      has been reported by many studies, with inconclusive results. We performed a meta
      analysis of cohort and case-control studies to provide a quantitative assessment
      of this association. METHODS: Relevant studies were identified by searching
      PubMed and Embase before December 2013 without restrictions. A total of 18
      studies involving 1,228,327 subjects were included in this meta-analysis. Summary
      relative risks were estimated using random effects models. RESULTS: The pooled
      relative risks of gastric cancer were 1.37 (95 % CI 1.18-1.59) for the highest
      versus lowest categories of red meat intake with significant heterogeneity among
      studies (P(heterogeneity) < 0.001, I(2) = 67.6 %). When stratified by the study
      design, the significant associations were observed in population-based case
      control studies (RR 1.58; 95 % CI 1.22-2.06; P(heterogeneity) < 0.001, I(2) =
      73.0 %) and hospital-based case-control studies (RR 1.63; 95 % CI 1.38-1.92;
      P(heterogeneity) = 0.284, I(2) = 19.1 %). However, no association was observed
      among cohort studies (RR 1.00; 95 % CI 0.83-1.20; P(heterogeneity) = 0.158, I(2)
      = 33.9 %). The significant association was also presented in the subgroup
      analysis by geographic area (Asia, Europe), publication year (>=2000), sample
      size (<1,000, >=1,000) and quality score (<7 stars, >=7 stars). The dose-response
      analysis associated every 100 g/day increment in red meat intake with a 17 %
      increased gastric cancer risk (RR 1.17; 95 % CI 1.05-1.32). A linear regression
      model further revealed that the risk of gastric cancer increased with increasing
      level of red meat consumption. CONCLUSIONS: Increased intake of red meat might be
      a risk factor for stomach cancer. Further larger prospective studies are
      warranted to verify this association.

PMID- 24682373
TI  - [Spermatocytic seminoma. A tumor with many faces].
AB  - Spermatocytic seminomas affect 0.3-0.8 per one million men. This tumor is not, as
      the name might suggest, a variant of classical seminoma but a distinct
      nosological entity, which differs markedly from all other germ cell tumors in its
      epidemiology, peculiar morphology, oncogenesis and clinical outcome. There are no
      racial differences in the incidence and risk factors are completely unknown.
      Patients are significantly older than is the case for other germ cell tumors with
      an average of 53.5 years; nevertheless, more than 25 % are younger than 40 years.
      Spermatocytic seminoma arises from differentiated spermatogonia, not from
      intratubular germ cell neoplasms. The tumor-specific gain of chromosome 9 seems
      to be the most important event in the oncogenesis. Conventional spermatocytic
      seminoma consists of three different cell types which give the tumor a highly
      aggressive appearance, although in actual fact, the tumor has a very favorable
      outcome, with few reported cases of general metastatic spread. Anaplastic
      spermatocytic seminoma, a recently described variant, also takes mostly a benign
      course; however, spermatocytic seminomas combined with sarcomas are extremely
      malignant. 

PMID- 24682374
TI  - Influence of preoperative biliary drainage on surgical outcome after
      pancreaticoduodenectomy: single centre experience.
AB  - PURPOSE: Controversy prevails on the impact of preoperative biliary drainage
      (PBD) on postoperative complications and clinical outcome of pancreatic cancer.
      We determined whether PBD is associated with increased morbidity and mortality
      rates after pancreaticoduodenectomy. METHODS: A total of 131 consecutive patients
      who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were
      included in this study. Overall, 57 % of jaundiced patients underwent PBD, while
      43 % were not drained. The impact of PBD on postoperative morbidity and mortality
      was evaluated by means of logistic regression analysis. The Kaplan-Meier method
      was applied to determine the effect of PBD on survival of patients with malignant
      lesions. RESULTS: Mortality and morbidity rate was 3 % and 54.6 %, respectively.
      PBD was demonstrated to be the unique predictor of complications (odds ration
      [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The
      jaundiced patients who were drained exhibited high frequencies of wound infection
      (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p <
      0.001). In addition, an increased frequency of pancreatic fistula emerged among
      drained patients compared to those who were not drained (p = 0.036). PBD did not
      affect survival of patient with malignant lesions. CONCLUSIONS: With the
      exception of the classical indications, PBD should be carefully evaluated in
      patients with resectable pancreatic cancer.

PMID- 24682377
TI  - Selective thoracic fusion in AIS curves: the definition of target outcomes
      improves the prediction of spontaneous lumbar curve correction (SLCC).
AB  - INTRODUCTION: The decision of when to use selective thoracic fusion (STF) and the
      prediction of spontaneous lumbar curve correction (SLCC) remain difficult. Using
      a novel methodological approach, the authors yielded for a better prediction of
      SLCC and analyzed the efficacy of anterior scoliosis correction and fusion (ASF).
      METHODS: A retrospective analysis of 273 patients treated with ASF for STF was
      performed. In total, 87 % of the patients showed a Lenke 1 curve pattern. The
      lumbar curve modifier was classified as A in 66 % of the patients, B in 21 % of
      the patients and C in 13 % of the patients. The fusion length averaged 6.7
      levels. The analysis included an assessment of radiographic deformity and
      correction, surgery characteristics, complications and revisions and clinical
      outcomes to improve the prediction of SLCC. Patients with a Type A-L, Type B or
      Type C modifier were stratified into a target follow-up lumbar curve (LC)
      category of <=20 degrees  or >20 degrees . Linear regression analyses were
      performed to assess the accuracy of predicting LC magnitude, and a multivariate
      logistic regression model was built using the following preoperative (preop)
      predictors: main thoracic curve (MTC), LC, MTC-bending and LC-bending. The output
      variable indicated whether a patient had an LC >20 degrees  at follow-up. A
      variable selection algorithm was applied to identify significant predictors. Two
      thresholds (cut-offs) were applied to the test sample to create high positive and
      negative prediction values. The data from 33 additional patients were gathered
      prospectively to create an independent test sample to learn how the model
      performed with independent data as a test of the generalizability of the model.
      RESULTS: The average patient age was 17 years, and the average follow-up period
      was 33 months. The MTC was 53.1 degrees  +/- 10.2 degrees  preoperatively, 29.8
      degrees  +/- 10.5 degrees  with bending and was 25.4 degrees  +/- 9.7 degrees  at
      follow-up (p < 0.01). The LC was 35.7 degrees  +/- 7.5 degrees  preoperatively,
      8.9 degrees  +/- 5.8 degrees  with bending, and 21.8 degrees  +/- 7.0 degrees  at
      follow-up (p < 0.01). After applying a variable selection algorithm, the preop LC
      [p < 0.02, odds ratio (OR) = 1.09] and preop LC-bending (p < 0.009, OR = 1.14)
      remained in the model as significant predictors. The performance of the linear
      regression model was tested in an independent test sample, and the difference
      between the observed and predicted values was only 1 degrees  +/- 4.5 degrees .
      Based on the test sample, the lower threshold was set to 25 %, and the upper
      threshold was set to 75 %. Patients with prediction values of 25-75 % were
      identified by the model, but by definition of the model, no prediction was made.
      In the test sample, 87 % of the patients were correctly classified as having an
      LC <=20 degrees  at follow-up, and 84 % of the patients were correctly classified
      as having an LC >20 degrees . The model test in the independent test sample
      revealed that 100 % of the patients were correctly classified as having an LC
      <=20 degrees , and 86 % of the patients were correctly classified as having an LC
      >20 degrees . CONCLUSION: After analyzing a sufficiently large sample of 273
      patients who underwent ASF for STF, significant predictors for SLCC were
      established and reported according to the surgical outcomes. Application of the
      prediction models can aid surgeons in the decision-making process regarding when
      to perform STF. Our results indicate that with stratification of outcomes into
      target curves (e.g., an LC <20 degrees ), future benchmarks for STF might be more
      conclusive.

PMID- 24682378
TI  - Does intraoperative cell salvage system effectively decrease the need for
      allogeneic transfusions in scoliotic patients undergoing posterior spinal fusion?
      A prospective randomized study.
AB  - PURPOSE: To determine the safety and efficacy of intraoperative cell salvage
      system in decreasing the need for allogeneic transfusions in a cohort of
      scoliosis patients undergoing primary posterior spinal fusion with segmental
      spinal instrumentation. METHODS: A total of 110 consecutive scoliosis patients
      undergoing posterior instrumented spinal fusion were randomized into two groups
      according to whether a cell saver machine for intraoperative blood salvage was
      used or not. Data included age, body mass index, perioperative hemoglobin levels,
      surgical time, levels fused, perioperative estimated blood loss, perioperative
      transfusions and incidence of transfusion-related complications. A Chi-square
      test and t tests were performed for intraoperative and perioperative allogeneic
      transfusion between groups. A regression analysis was performed between selected
      covariates to investigate the predictive factors of perioperative transfusion.
      RESULTS: Perioperative allogenic blood transfusion rate was lower in the cell
      saver group (14.5 versus 32.7%, p = 0.025). Mean intraoperative red blood cell
      transfusion requirement was also lower (0.21 U/pt versus 0.58 U/pt, p = 0.032). A
      multivariate analysis demonstrated that no. of fused segments (OR: 1.472; p =
      0.005), preoperative hemoglobin level (OR: 0.901; p = 0.001), and the use of cell
      saver system (OR: 0.133; p = 0.003) had a trend toward significance in predicting
      likelihood of transfusion. CONCLUSIONS: Cell saver use significantly reduces the
      need for allogeneic blood in spine deformity surgery, particularly in patients
      with low preoperative hemoglobin or longer operation time. This study confirms
      the utility of routine cell saver use during PSF with segmental spinal
      instrumentation for scoliosis patients.

PMID- 24682379
TI  - Efficacy of vildagliptin versus sulfonylureas as add-on therapy to metformin:
      comparison of results from randomised controlled and observational studies.
AB  - AIMS/HYPOTHESIS: Randomised control trials (RCTs) do not always reflect real-life
      outcomes for glucose-lowering drugs. In this work we compared RCT and real-life
      data on the efficacy of the dipeptidyl peptidase-IV (DPP-4) inhibitor
      vildagliptin or sulfonylureas when added to metformin. METHODS: Data were pooled
      from five RCTs examining vildagliptin (n = 2,788) and sulfonylureas (glimepiride
      [n = 1,259] or gliclazide [n = 433]), added to metformin. For real-life
      conditions, data were extracted from an observational study examining
      vildagliptin (n = 7,002) or sulfonylureas (n = 3,702), added to metformin
      monotherapy. Linear regression analyses were performed between the baseline HbA1c
      and the change in HbA1c (Delta HbA1c) after 24 weeks. RESULTS: Baseline HbA1c
      correlated to Delta HbA1c (r (2) = 0.36, slope = -0.54 [95% CI -0.55, -0.53; p <
      0.0001]) for both treatments. With sulfonylureas, the slope of the correlation
      was steeper in the observational study than in RCTs (interaction coefficient = 
      0.327, p < 0.001), whereas for vildagliptin, the slope was virtually identical in
      the observational study and the RCTs (interaction coefficient = 0.024, p =
      0.175). For any given baseline HbA1c, Delta HbA1c with sulfonylureas was smaller
      in real life than in RCTs, whereas Delta HbA1c with vildagliptin was the same.
      CONCLUSIONS/INTERPRETATIONS: When comparing RCT to real-life data, the decrease
      in HbA1c from baseline with sulfonylurea treatment is smaller in real life than
      in RCTs, whereas the reduction with vildagliptin is essentially the same,
      suggesting that the full power of treatment is retained in real life for
      vildagliptin but not for sulfonylureas, possibly due to fear of hypoglycaemia.

PMID- 24682380
TI  - Suppression of retinal neovascularization by small interfering RNA targeting PGC
      1alpha.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      is a key coordinator of gene programs in metabolism and energy homeostasis in
      mammals. The aim of this study was to determine whether PGC-1alpha is involved in
      the transcriptional regulation of retinal neovascularization in oxygen-induced
      retinopathy (OIR). The expression of PGC-1alpha in the retina of mice with OIR
      was detected by real-time polymerase chain reaction (PCR) and western blot
      analysis. Mice with OIR were administered small interfering RNA (siRNA) targeting
      PGC-1alpha by intravitreal injection, and the effects of PGC-1alpha siRNA were
      confirmed by fluorescein angiography and quantification of pre-retinal
      neovascular nuclei in the retinal sections. PGC-1alpha was upregulated at both
      the mRNA and protein level under hypoxic conditions. Retinal neovascularization
      was inhibited by PGC-1alpha siRNA. Furthermore, PGC-1alpha mRNA and protein
      levels were also reduced by PGC-1alpha siRNA, which were detected by real-time
      PCR and western blot analysis. The downregulation of PGC-1alpha expression
      resulted in the reduction of vascular endothelial growth factor (VEGF) expression
      in the mice. In conclusion, siRNA targeting PGC-1alpha inhibits retinal
      neovascularization by downregulating the expression of PGC-1alpha and VEGF in the
      murine retina. Therefore, PGC-1alpha represents a potential therapeutic target
      for ischemia-induced retinal diseases and other ocular neovascular diseases.

PMID- 24682381
TI  - GPC5, a tumor suppressor, is regulated by miR-620 in lung adenocarcinoma.
AB  - In the current study, a proportion of lung adenocarcinoma was shown to reduce
      GPC5 expression in the absence of transcriptional silencing of the tumor
      suppressor gene, GPC5, by aberrant methylation of CpG islands. It was
      hypothesized that the loss of GPC5 expression is associated with upregulation of
      miR-620 in human lung adenocarcinoma tissue compared with the matched normal lung
      tissue. The downregulation of GPC5 in lung adenocarcinoma cell lines is regulated
      by miR-620 through binding of the 3'-untranslated region. Furthermore, blockage
      of miR-620 inhibited the proliferation, migration and invasion of lung
      adenocarcinoma cells by directly regulating GPC5, and GPC5 knockdown eliminates
      this phenotype. These results provided a novel insight into the mechanism of
      miRNA regulation in lung adenocarcinoma. 

PMID- 24682383
TI  - The effect of asthma education program on knowledge of school teachers: a
      randomized controlled trial.
AB  - The purpose of this study was to examine the effect of an asthma education
      program on schoolteachers' knowledge. Pre-test-post-test experimental randomized
      controlled design was used. A multistage-cluster sampling technique was used to
      randomly select governorate, primary schools, and schoolteachers. Schoolteachers
      were randomly assigned either to the experimental group (n = 36) and attended
      three educational sessions or to the control group (n = 38) who did not receive
      any intervention. Knowledge about asthma was measured using the Asthma General
      Knowledge Questionnaire for Adults (AGKQA). The results indicated that teachers
      in the experimental group showed significantly (p < .001) higher knowledge of
      asthma in the first post-test and the second post-test compared with those in the
      control group. Implementing asthma education enhanced schoolteachers' knowledge
      of asthma. The asthma education program should target schoolteachers to improve
      knowledge about asthma. 

PMID- 24682385
TI  - How safe is bladder urine culture for the management of percutaneous procedures?

PMID- 24682384
TI  - Massive blood transfusion after the first cut in liver transplantation predicts
      renal outcome and survival.
AB  - INTRODUCTION: Transfusion requirements of blood products may provide useful
      prognostic factors for the prediction of short-term patient mortality and renal
      outcome after liver transplantation. PATIENTS AND METHODS: Two hundred ninety-one
      consecutive liver transplants in adults were analysed retrospectively. Combined
      and living-related liver transplants were excluded. The amount of transfused
      packed red blood cells (PRBC) and units of platelets (UP) within the first 48 h
      were investigated as prognostic factors to predict short-term patient mortality
      and renal outcome. Receiver operating characteristic (ROC) curve analysis with
      area under the curve (AUC), Hosmer-Lemeshow tests and Brier scores were used to
      calculate overall model correctness, model calibration and accuracy of prognostic
      factors. Cut-off values were determined with the best Youden index. RESULTS: The
      potential clinical usefulness of PRBC as a prognostic factor to predict 30-day
      mortality (cut-off 17.5 units) and post-transplant haemodialysis (cut-off 12.5
      units) could be demonstrated with AUCs >0.7 (0.712 and 0.794, respectively).
      Hosmer-Lemeshow test results and Brier scores indicated good overall model
      correctness, model calibration and accuracy. The UP proved as an equally
      clinically useful prognostic factor to predict end-stage renal disease (cut-off
      3.5 units; AUC = 0.763). The association of cut-off levels of PRBC with patient
      survival (p < 0.001, log-rank test) and dialysis-free survival (p < 0.001, log
      rank test) was significant (cut-off levels 17.5 and 12.5 units, respectively) as
      well as the association of UP with dialysis-free survival (p < 0.001, log-rank
      test) (cut-off level 3.5 units). CONCLUSIONS: The impressive discriminative power
      of these simple prognostic factors for the prediction of outcome after liver
      transplantation emphasizes the relevance of strategies to avoid excessive
      transfusion requirements.

PMID- 24682386
TI  - Comparing the imperfect with the imperfect: the imprecise science of assessing
      the risk and benefits of anticoagulation in atrial fibrillation.

PMID- 24682387
TI  - Lack of concordance between empirical scores and physician assessments of stroke
      and bleeding risk in atrial fibrillation: results from the Outcomes Registry for
      Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry.
AB  - BACKGROUND: Physicians treating patients with atrial fibrillation (AF) must weigh
      the benefits of anticoagulation in preventing stroke versus the risk of bleeding.
      Although empirical models have been developed to predict such risks, the degree
      to which these coincide with clinicians' estimates is unclear. METHODS AND
      RESULTS: We examined 10 094 AF patients enrolled in the Outcomes Registry for
      Better Informed Treatment of AF (ORBIT-AF) registry between June 2010 and August
      2011. Empirical stroke and bleeding risks were assessed by using the congestive
      heart failure, hypertension, age >=75 years, diabetes mellitus, and previous
      stroke or transient ischemic attack (CHADS2) and Anticoagulation and Risk Factors
      in Atrial Fibrillation (ATRIA) scores, respectively. Separately, physicians were
      asked to categorize their patients' stroke and bleeding risks: low risk (<3%);
      intermediate risk (3%-6%); and high risk (>6%). Overall, 72% (n=7251) in ORBIT-AF
      had high-risk CHADS2 scores (>=2). However, only 16% were assessed as high stroke
      risk by physicians. Although 17% (n=1749) had high ATRIA bleeding risk (score
      >=5), only 7% (n=719) were considered so by physicians. The associations between
      empirical and physician-estimated stroke and bleeding risks were low (weighted
      Kappa 0.1 and 0.11, respectively). Physicians weighed hypertension, heart
      failure, and diabetes mellitus less significantly than empirical models in
      estimating stroke risk; physicians weighted anemia and dialysis less
      significantly than empirical models when estimating bleeding risks.
      Anticoagulation use was highest among patients with high stroke risk, assessed by
      either empirical model or physician estimates. In contrast, physician and
      empirical estimates of bleeding had limited impact on treatment choice.
      CONCLUSIONS: There is little agreement between provider-assessed risk and
      empirical scores in AF. These differences may explain, in part, the current
      divergence of anticoagulation treatment decisions from guideline recommendations.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01165710.

PMID- 24682388
TI  - Aloperine induces G2/M phase cell cycle arrest and apoptosis in HCT116 human
      colon cancer cells.
AB  - Aloperine (ALO) is a quinolizidine alkaloid extracted from the leaves of Sophora
      alopecuroides (S. alopecuroides) and possesses anti-inflammatory, anti
      allergenic, antitumor, and antiviral effects. In this study, when compared with
      seven other types of alkaloids extracted from S. alopecuroides, ALO treatment
      produced the most potent effects against HCT116 colon cancer cell types. ALO
      inhibited proliferation and induced apoptosis in HCT116 cells in a dose- and time
      dependent manner as detected by MTT, clonogenic survival, and flow cytometric
      assays. Results of the western blot analysis and qPCR revealed that ALO increased
      the protein and mRNA of Bax and decreased Bcl-2 via the mitochondrial death
      pathway. In addition, ALO induced cell cycle arrest at the G2/M phase with a
      concomitant increase in p21 and p53 and a decrease in cyclin D1 and B1. ALO also
      inhibited phosphatidylinositol 3-kinase/Akt and JAK/Stat3. Generally, ALO exerted
      a significant anti-proliferative effect via apoptotic and cell cycle arrest
      induction in HCT116 cells. These results suggested that ALO should be
      investigated further as an agent of chemotherapeutic activity in human colon
      cancer.

PMID- 24682389
TI  - Cryptotanshinone inhibits lung tumorigenesis and induces apoptosis in cancer
      cells in vitro and in vivo.
AB  - Cryptotanshinone is one of the compounds extracted from the root of Salvia
      miltiorrhiza Bunge. Unlike other tanshinones, only a small number of studies have
      focused on cryptotanshinone for medical treatment. In the present study, the A549
      lung cancer cell line and xenograft models of human lung tumors were used to
      assess the anti-cancer effect of cryptotanshinone. The effect of cryptotanshinone
      on human lung cancer, including growth inhibition, cell cycle arrest and
      apoptosis factors, were identified in vitro, and inhibition of tumor formation,
      improvement of body condition as well as pathological apoptotic effects were
      detected in vivo. These results suggested that cryptotanshinone is a potential
      drug for the treatment and prevention of human lung cancer.

PMID- 24682390
TI  - Prognostic significance of serum lactate dehydrogenase level in osteosarcoma: a
      meta-analysis.
AB  - BACKGROUND: A number of studies have investigated the role of serum lactate
      dehydrogenase (LDH) level in patients with osteosarcoma but have yielded
      inconsistent and inconclusive results. Thus, we conducted a meta-analysis to
      assess its prognostic value more precisely. METHODS: Systematic computerized
      searches of PubMed, Embase and Web of Science databases were performed. The
      pooled hazard ratio (HR) with 95 % confidence intervals (95 % CI) of overall
      survival was used to assess the prognostic role of serum LDH level. RESULTS: Ten
      studies published between 1997 and 2013 with a total of 943 osteosarcoma patients
      were included. Overall, the pooled HR for all ten eligible studies evaluating
      high LDH level on overall survival was 1.92(95 % CI 1.53-2.40). Sensitivity
      analysis suggested that the pooled HR was stable and omitting a single study did
      not change the significance of the pooled HR. Funnel plots and Egger's tests
      revealed there was some possibility of publication bias risk in the meta
      analysis. CONCLUSION: This meta-analysis shows that high serum LDH level is
      obviously associated with lower overall survival rate in patients with
      osteosarcoma, and it is an effective biomarker of prognosis.

PMID- 24682391
TI  - Membrane flickering of the human erythrocyte: constrained random walk used with
      Bayesian analysis.
AB  - The involvement of adenosine triphosphate (ATP) in erythrocyte (red blood cell;
      RBC) membrane flickering is of particular interest, because ATP turnover in the
      cell as a whole is not yet fully accounted for. We sought the origins of
      flickering by deriving a mathematical model of it, on the basis of the idea of
      thermally driven collisions of small molecules with the membrane, which responds
      like an over-damped spring. The model gave simulated responses that were similar
      to a constrained random walk and had the same frequency-spectral characteristics
      of membrane displacement as those recorded from RBCs by use of differential
      interference contrast light microscopy. Bayesian analysis was used as the basis
      for determination, from experimental results, of the values of the parameters in
      the model. The analysis was used in the accompanying article in which we
      investigated the response of membrane flickering to different effector molecules
      and physicochemical conditions. The results implied ATP was involved only
      indirectly in membrane flickering. 

PMID- 24682392
TI  - Lysozyme binding to tethered bilayer lipid membranes prepared by rapid solvent
      exchange and vesicle fusion methods.
AB  - Tethered bilayer lipid membranes (tBLMs) are important tools for studying protein
      lipid interactions. The widely used methodology for the preparation of these
      membranes is the fusion of phospholipid vesicles from an aqueous medium onto an
      anchored phospholipid layer. The preparation of phospholipid vesicles is a long
      and tedious procedure. There is another simple method, rapid solvent exchange,
      for preparing lipid membranes. However, there is a lack of information on the
      effects of the preparation method of tBLMs on their interactions with proteins.
      Therefore, we present in this paper a comparative study on the binding of
      lysozyme onto tBLMs prepared by the abovementioned methods. The prepared tBLMs
      have either zwitterionic or anionic characteristics. The results show that
      lysozyme binding onto the prepared tBLMs is unaffected by the preparation method
      of the tBLMs, suggesting that the tedious fusion method might be replaced by the
      simple rapid solvent exchange method without altering the level of protein-lipid
      interactions.

PMID- 24682393
TI  - Effect of aging on carotid baroreflex control of blood pressure and leg vascular
      conductance in women.
AB  - Recent work suggests that beta-adrenergic vasodilation offsets alpha-adrenergic
      vasoconstriction in young women, but this effect is lost after menopause. Given
      these age-related vascular changes, we tested the hypothesis that older women
      would exhibit a greater change in vascular conductance following baroreflex
      perturbation compared with young women. In 10 young (21 +/- 1 yr) and 10 older
      (62 +/- 2 yr) women, mean arterial pressure (MAP; Finometer), heart rate (HR),
      cardiac output (CO; Modelflow), total vascular conductance (TVC), and leg
      vascular conductance (LVC, duplex-Doppler ultrasound) were continuously measured
      in response to 5-s pulses of neck suction (NS; -60 Torr) and neck pressure (NP;
      +40 Torr) to simulate carotid hypertension and hypotension, respectively.
      Following NS, decreases in MAP were similar between groups; however, MAP peak
      response latency was slower in older women (P < 0.05). Moreover, at the time of
      peak MAP, increases in LVC (young, -11.5 +/- 3.9%LVC vs. older, +19.1 +/-
      7.0%LVC; P < 0.05) and TVC were greater in older women, whereas young women
      exhibited larger decreases in HR and CO (young, -10 +/- 3% CO vs. older, +0.8 +/-
      2% CO; P < 0.05). Following NP, increases in MAP were blunted (young, +14 +/- 1
      mmHg vs. older, +8 +/- 1 mmHg; P < 0.05) in older women, whereas MAP response
      latencies were similar. Interestingly, decreases in LVC and TVC were similar
      between groups, but HR and CO (young, +7.0 +/- 2% CO vs. older, -4.0 +/- 2% CO; P
      < 0.05) responses were attenuated in older women. These findings suggest that
      older women have greater reliance on vascular conductance to modulate MAP via
      carotid baroreflex, whereas young women rely more on cardiac responsiveness.
      Furthermore, older women demonstrate a blunted ability to increase MAP to
      hypotensive stimuli.

PMID- 24682394
TI  - Matrix elasticity regulates the optimal cardiac myocyte shape for contractility.
AB  - Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis,
      and decreased myocyte length-to-width aspect ratio. Ventricular thickening is
      considered compensatory because it reduces wall stress, but the functional
      consequences of cell shape remodeling in this pathological setting are unknown.
      We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize
      contractility when the extracellular matrix becomes stiffer due to conditions
      such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes
      into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes
      on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin
      alignment was unaffected by matrix elasticity, but sarcomere content was
      typically higher on stiff gels. Microtubule polymerization was higher on stiff
      gels, implying increased intracellular elastic modulus. On moderate gels,
      myocytes with moderate aspect ratios (~7:1) generated the most peak systolic work
      compared with other cell shapes. However, on stiffer gels, low aspect ratios
      (~2:1) generated the most peak systolic work. To compare the relative
      contributions of intracellular vs. extracellular elasticity to contractility, we
      developed an analytical model and used our experimental data to fit unknown
      parameters. Our model predicted that matrix elasticity dominates over
      intracellular elasticity, suggesting that the extracellular matrix may
      potentially be a more effective therapeutic target than microtubules. Our data
      and model suggest that myocytes with lower aspect ratios have a functional
      advantage when the elasticity of the extracellular matrix decreases due to
      conditions such as fibrosis, highlighting the role of the extracellular matrix in
      cardiac disease. 

PMID- 24682396
TI  - A Perfect Storm: Care Transitions for Vulnerable Older Adults Discharged Home
      From the Emergency Department Without a Hospital Admission.
AB  - PURPOSE OF THE STUDY: The purpose of the study was to describe, from the
      perspectives of emergency department (ED) providers, factors that influence
      quality and safety of transitions home from the ED for vulnerable older adults.
      DESIGN AND METHODS: A grounded theory approach was used to analyze data from 9
      focus groups conducted with ED staff that included representatives from nursing,
      medicine, pharmacy, social work, and respiratory therapy. RESULTS: From the
      perspectives of these care providers, 5 antecedent concepts contribute to the
      perceived quality and safety of transitions from the ED to home. These 5 concepts
      include the nature of geriatric presentations, provider knowledge, consumer
      knowledge, the ED resource base, and health care system fractures. Co-occurrence
      and interaction among the 5 identified antecedents set up conditions for what one
      focus group participant described as a perfect storm. IMPLICATIONS: Older adults
      discharged home from the ED without a hospital admission are an increasingly
      important but understudied group within the transitional care literature.
      Although they share some similarities with those undergoing different health
      transitions, their unique needs and the specific characteristics of ED care
      require a novel approach. The model that emerged in this study provides direction
      for understanding the complex and interrelated aspects of their transitional care
      needs.

PMID- 24682395
TI  - Tempol improves cutaneous thermal hyperemia through increasing nitric oxide
      bioavailability in young smokers.
AB  - We recently found that young cigarette smokers display cutaneous vascular
      dysfunction relative to nonsmokers, which is partially due to reduced nitric
      oxide (NO) synthase (NOS)-dependent vasodilation. In this study, we tested the
      hypothesis that reducing oxidative stress improves NO bioavailability, enhancing
      cutaneous vascular function in young smokers. Ten healthy young male smokers, who
      had smoked for 6.3 +/- 0.7 yr with an average daily consumption of 9.1 +/- 0.7
      cigarettes, were tested. Cutaneous vascular conductance (CVC) during local
      heating to 42 degrees C at a rate of 0.1 degrees C/s was evaluated as laser
      Doppler flux divided by mean arterial blood pressure and normalized to maximal
      CVC, induced by local heating to 44 degrees C plus sodium nitroprusside
      administration. We evaluated plateau CVC during local heating, which is known to
      be highly dependent on NO, at four intradermal microdialysis sites with 1) Ringer
      solution (control); 2) 10 MUM 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl
      (tempol), a superoxide dismutase mimetic; 3) 10 mM N(omega)-nitro-l-arginine (l
      NNA), a nonspecific NOS inhibitor; and 4) a combination of 10 MUM tempol and 10
      mM l-NNA. Tempol increased plateau CVC compared with the Ringer solution site
      (90.0 +/- 2.3 vs. 77.6 +/- 3.9%maximum, P = 0.028). Plateau CVC at the
      combination site (56.8 +/- 4.5%maximum) was lower than the Ringer solution site
      (P < 0.001) and was not different from the l-NNA site (55.1 +/- 4.6%maximum, P =
      0.978), indicating the tempol effect was exclusively NO dependent. These data
      suggest that in young smokers, reducing oxidative stress improves cutaneous
      thermal hyperemia to local heating by enhancing NO production. 

PMID- 24682397
TI  - Everything you need to know about distal renal tubular acidosis in autoimmune
      disease.
AB  - Renal acid-base homeostasis is a complex process, effectuated by bicarbonate
      reabsorption and acid secretion. Impairment of urinary acidification is called
      renal tubular acidosis (RTA). Distal renal tubular acidosis (dRTA) is the most
      common form of the RTA syndromes. Multiple pathophysiologic mechanisms, each
      associated with various etiologies, can lead to dRTA. The most important
      consequence of dRTA is (recurrent) nephrolithiasis. The diagnosis is based on a
      urinary acidification test. Potassium citrate is the treatment of choice. 

PMID- 24682398
TI  - Pseudo-Behcet's disease associated with tuberculosis: a case report and review of
      the literature.
AB  - Orogenital ulcer is one of the clinical manifestations of Behcet's disease (BD).
      However, orogenital ulcer may be observed in various conditions, such as complex
      aphthous dermatitis and herpes simplex virus infections. Therefore, orogenital
      ulcer along with skin lesions, including acne or erythema nodosum, may be
      misdiagnosed as BD, but is actually pseudo-BD instead. We report here a case of
      pseudo-BD due to Mycobacterium tuberculosis infection in which anti-tuberculous
      treatment resulted in complete resolution. Furthermore, we review the literature
      regarding the association of BD and M. tuberculosis infection.

PMID- 24682400
TI  - BMJ Awards 2014. Berwick Patient Safety Team: making the NHS a safer place.

PMID- 24682399
TI  - Influence of blood prostate specific antigen levels at age 60 on benefits and
      harms of prostate cancer screening: population based cohort study.
AB  - OBJECTIVE: To determine the relative risks of prostate cancer incidence,
      metastasis, and mortality associated with screening by serum prostate specific
      antigen (PSA) levels at age 60. DESIGN: Population based cohort study. SETTING:
      General male population of Sweden taking part in a screening trial in Gothenburg
      or participating in a cardiovascular study, the Malmo Preventive Project.
      PARTICIPANTS: The screened group consisted of 1756 men aged 57.5-62.5
      participating in the screening arm of the Gothenburg randomized prostate cancer
      screening trial since 1995. The unscreened group consisted of 1162 men, born in
      1921, participating in the Malmo Preventive Project, with PSA levels measured
      retrospectively in stored blood samples from 1981. INTERVENTION: PSA screening
      versus no screening. MAIN OUTCOME MEASURES: Incidence rate ratios for the effect
      of screening on prostate cancer diagnosis, metastasis, and death by PSA levels at
      age 60. RESULTS: The distribution of PSA levels was similar between the two
      cohorts. Differences in benefits by baseline PSA levels were large. Among men
      with baseline levels measured, 71.7% (1646/2295) had a PSA level <2 ng/mL. For
      men aged 60 with PSA level <2 ng/mL, there was an increase in incidence of 767
      cases per 10,000 without a decrease in prostate cancer mortality. For men with
      PSA levels >= 2 ng/mL, the reduction in cancer mortality was large, with only 23
      men needing to be screened and six diagnosed to avoid one prostate cancer death
      by 15 years. CONCLUSIONS: The ratio of benefits to harms of PSA screening varies
      noticeably with blood PSA levels at age 60. For men with a PSA level <1 ng/mL at
      age 60, no further screening is recommended. Continuing to screen men with PSA
      levels >2 ng/mL at age 60 is beneficial, with the number needed to screen and
      treat being extremely favourable. Screening men with a PSA level of 1-2 ng/mL is
      an individual decision to be based on a discussion between patient and doctor.

PMID- 24682401
TI  - Most UK cases of vCJD are being detected, experts tell MPs.

PMID- 24682402
TI  - Indian hospitals must explain why they refused to treat patients on government
      scheme.

PMID- 24682403
TI  - The inferior emissary vein: a reliable landmark for right adrenal vein sampling.
AB  - BACKGROUND: Right adrenal vein (RAV) catheterization can be a very challenging
      step in adrenal venous sampling (AVS). Visualization of the inferior emissary
      vein (IEV) may be an indication of successful RAV catheterization. PURPOSE: To
      compare the rate of successful RAV sampling in the presence of the IEV. MATERIAL
      AND METHODS: Retrospective review of all consecutive patients with PA who
      underwent AVS between April 2009 and April 2012 was performed. A total of 30
      patients were identified. Procedural images, cortisol, and aldosterone values
      obtained from sampling of the RAV and inferior vena cava (IVC) were reviewed.
      Cortisol measurements obtained from RAV samples were divided by measurements from
      the infra-renal IVC blood samples in order to calculate the selectivity index
      (SI). An SI >3 was considered indicative of technically successful RAV sampling.
      RESULTS: RAV sampling was considered technically successful in 29 out of 30 cases
      (97%). In cases of successful RAV sampling (29 patients), the IEV was identified
      in 25 patients (86%). The IEV was visualized in isolation in 16 patients (64%),
      and in conjunction with visualization of the RAV or right adrenal gland stain in
      nine patients (36%). The IEV was not visualized in the one case of unsuccessful
      RAV sampling. Visualizing the IEV had a sensitivity of 86.2% for successful RAV
      sampling. CONCLUSION: The IEV may serve as a reliable landmark for the RAV during
      RAV sampling.

PMID- 24682404
TI  - Bosniak classification system: inter-observer and intra-observer agreement among
      experienced uroradiologists.
AB  - BACKGROUND: The Bosniak classification is a diagnostic tool for the
      differentiation of cystic changes in the kidney. The process of categorizing
      renal cysts may be challenging, involving a series of decisions that may affect
      the final diagnosis and clinical outcome such as surgical management. PURPOSE: To
      investigate the inter- and intra-observer agreement among experienced
      uroradiologists when categorizing complex renal cysts according to the Bosniak
      classification. MATERIAL AND METHODS: The original categories of 100 cystic renal
      masses were chosen as "Gold Standard" (GS), established in consensus by two
      experienced uroradiologists. Three experienced uroradiological readers were
      blinded from the previous CT reports. Weighted kappa was calculated to assess
      agreement, defined as: fair, 0.21-0.40; moderate, 0.41-0.60; good, 0.61-0.80; and
      very good, 0.81-1.00. RESULTS: For readers the distribution of correctly
      classified lesions were as follows: BI, 95-100%; BII, 59-93%; BIIF, 54-92%; BIII,
      58-95%; and B IV, 77-100% for the first review. Weighted kappa for inter
      observer/intra-observer variation was for Reader A: 0.85/0.99, Reader B:
      0.97/0.99, and Reader C: 0.98/0.99, (P <= 0.001). CONCLUSION: According to the
      calculated weighted kappa all readers performed "very good" for both inter
      observer and intra-observer variation. Most variation was seen in cysts
      catagorized as Bosniak II, IIF, and III. These results show that radiologists who
      evaluate complex renal cysts routinely may apply the Bosniak classification
      reproducibly.

PMID- 24682405
TI  - Interpretation of automated breast ultrasound (ABUS) with and without knowledge
      of mammography: a reader performance study.
AB  - BACKGROUND: Automated breast ultrasonography (ABUS) has the potential to be an
      important adjunct to mammography in women with dense breasts. PURPOSE: To compare
      reader performance and inter-observer variation of ABUS alone and in combination
      with mammography. MATERIAL AND METHODS: This retrospective study had ethical
      committee approval. All women gave written informed consent. One hundred and
      fourteen breasts in 90 women examined by digital mammography and ABUS were
      interpreted by five radiologists using BI-RADS categories. The 114 breasts
      included 38 cancers and 76 normal or benign findings. In the first reading
      session ABUS only was interpreted, and in the second ABUS plus digital
      mammography. Image interpretations were done without knowledge of clinical or
      imaging results. A consensus panel analyzed false negative and false positive
      interpretations. Reading time was recorded for one radiologist. AUC was used for
      performance measurement, and kappa statistic for inter-observer variability.
      RESULTS: Mean size for cancers was 16.2 mm; area under the curve (AUC) values for
      ABUS alone and for combined reading were, respectively: reader A, 0.592-0.744;
      reader B, 0.740-0.947; reader, C 0.759-0.823; reader D, 0.670-0.688; reader E,
      0.904-0.923; and all readers combined 0.730-0.823. The higher AUC for combined
      reading was statistically significant (P < 0.05) for reader B and for all
      readers. There was a considerable inter-observer variability. Observer agreement
      revealed following kappa values for ABUS alone and combined reading,
      respectively: reader A, 0.22-0.30; reader B, 0.33-0.44; reader C, 0.32-0.39;
      reader D, 0.07-0.14; and reader E, 0.34-0.43. Shadowing from dense parenchyma was
      the most common cause of false positive ABUS interpretations. Mean interpretation
      time for a bilateral normal ABUS examination was 9 min. CONCLUSION: Observer
      agreement was higher and all radiologists improved diagnostic performance using
      combined ABUS and mammography interpretation. Combined reading should be standard
      if ABUS is implemented in screening of women with dense breasts.

PMID- 24682406
TI  - Respiratory gated and prolonged acquisition 18F-FDG PET improve preoperative
      assessment of colorectal liver metastases.
AB  - BACKGROUND: Detection of small liver metastases from colorectal cancer by 18F-FDG
      PET/CT is hampered by high physiologic uptake in the liver parenchyma and
      respiratory movements during image acquisition. PURPOSE: To investigate whether
      two tailored 18F-FDG PET liver acquisitions (prolonged liver acquisition time [PL
      PET] and repeated breath-hold respiratory gated liver acquisition [RGL-PET])
      would improve detection of colorectal liver metastases, when added to a standard
      whole body PET (WB-PET). MATERIAL AND METHODS: Twenty consecutive patients
      referred to our hospital for surgical treatment of colorectal liver metastases
      diagnosed with contrast-enhanced CT underwent preoperative 18F-FDG PET/CT
      tailored for detection of liver metastases. Concordance between preoperative
      imaging results and true findings (histology and/or follow-up imaging) as well as
      changes in clinical management, based on 18F-FDG PET/CT findings, were
      documented. Background noise, defined as the standard deviation measured in a
      reference region within the normal liver parenchyma, was compared between the
      three 18F-FDG PET/CT protocols. RESULTS: WB-PET, PL-PET, and RGL-PET showed
      suspicious liver lesions in 18 out of 20 patients. Compared to WB-PET alone, the
      combination of PL-PET and RGL-PET showed additional lesions in the liver in seven
      out of the 18 patients. The combination of all three PET acquisitions changed
      clinical management in four patients. Two patients with negative PET results were
      later found to have benign liver lesions. CONCLUSION: The addition of tailored
      liver-specific 18F-FDG PET/CT protocols (PL-PET and RGL-PET) to a WB-PET,
      improved the detection of intrahepatic colorectal metastases, compared to WB-PET
      alone. Such add-ons can change clinical patient management of potentially
      resectable colorectal liver metastases.

PMID- 24682407
TI  - Primary renal synovial sarcoma: computed tomography imaging findings.
AB  - BACKGROUND: A synovial sarcoma arising from the kidney is extremely rare. To
      date, few data are available on their radiological features. PURPOSE: To identify
      the computer tomography (CT) imaging findings of primary renal synovial sarcomas
      (PRSSs). MATERIAL AND METHODS: Five cases of PRSS confirmed by histopathological
      and cytogenetic studies were retrospectively analyzed. All patients had undergone
      unenhanced and multiphase enhanced CT examinations (one patient underwent CT
      twice). The CT characteristics, including shape, size, margin, attenuation, and
      enhancement pattern after intravenous contrast medium injection, were analyzed.
      RESULTS: The study involved two female and three male patients (mean age, 27.4
      years; range, 15-43 years). Unenhanced CT showed completely or partly well
      defined masses, with heterogeneous (n = 5) or homogeneous (n = 1) patchy low
      density. On multiphase contrast-enhanced CT, in five of the six CT examinations,
      the tumors appeared as solid-cystic masses with cyst walls or pseudo-capsules,
      and demonstrated moderately heterogeneous (n = 5) and/or septate enhancement (n =
      2), with a "rapid wash-in and slow wash-out" pattern of enhancement in the solid
      component. Only one tumor showed a simple cyst appearance and developed an
      irregular, intratumoral, septate soft density 8 months later. A renal vein and
      inferior vena cava thrombus was noticed in one patient, while lymphadenopathy was
      not observed in any patient. CONCLUSION: PRSS should be included in the
      differential diagnosis when an adolescent or young adult presents with a renal
      neoplasm appearing as a solid-cystic mass with well-defined borders, a cystic
      wall or pseudo-capsule, heterogeneous or septate enhancement, a "rapid wash-in
      and slow wash-out" pattern of enhancement in the solid component, and no sign of
      lymphadenopathy.

PMID- 24682408
TI  - Posture-induced changes of ocular vestibular evoked myogenic potentials suggest a
      modulation by intracranial pressure.
AB  - Ocular vestibular evoked myogenic potentials (oVEMPs) represent extraocular
      muscle activity in response to vestibular stimulation. We sought to investigate
      whether oVEMPs are modulated by increasing intracranial pressure (ICP). Air
      conducted oVEMPs were elicited in 20 healthy subjects lying supine on a tilt
      table. In order to elevate the ICP, the table was stepwise tilted from the
      horizontal plane to a 30 degrees  declination, corresponding to a 0 degrees , 10
      degrees , 20 degrees  and 30 degrees  head-down position. At each inclination
      angle, oVEMP recording was performed in two head positions: (1) the head in line
      with the body and (2) the head positioned horizontally with the body tilted. When
      tilting both the body and head, oVEMP amplitudes gradually declined from 4.59 MUV
      at 0 degrees  to 2.24 MUV at 30 degrees  head-down position, revealing a highly
      significant reduction in amplitudes for all tilt angles when compared to the
      baseline value (p < 0.001). In parallel, the response prevalence decreased and
      latencies prolonged. Similar effects were observed when the body was tilted but
      the head positioned horizontally, even though the decrease in oVEMP amplitudes
      was less pronounced. A gravitoinertial force effect upon the otolith organs could
      thereby be excluded as a possible confounder. Hence, oVEMPs were most likely
      modulated by increasing ICP. In the range of the horizontal plane to a 30 degrees
      head-down tilt, there was a linear correlation between oVEMP amplitudes and the
      inclination angle. oVEMPs might in principle be suited for non-invasive ICP
      monitoring.

PMID- 24682409
TI  - Molecular cloning, modeling and differential expression of a gene encoding a
      silent information regulator-like protein from Sporothrix schenckii.
AB  - Sporothrix schenckii (S. schenckii) is a dimorphic fungus that produces
      lymphocutaneous lesions. The signature characteristic of S. schenckii is a
      temperature-induced phase transition. Silent information regulator (Sir) has been
      proven to be involved in phenotypic switching in Saccharomyces cerevisiae (S.
      cerevisiae) and Candida albicans (C. albicans) by organizing chromatin structure.
      In this study, we isolated and characterized a Sir homologue gene, designated as
      SsSir2, from the yeast form of S. schenckii. The full-length SsSir2 cDNA sequence
      is 1753 bp in size and contains an open reading frame of 1329 bp encoding 442
      amino acids. The predicted molecular mass of SsSir2 is 48.1 kDa with an estimated
      theoretical isoelectric point of 4.6. The SsSir2 kinase domain shows a 78%
      identity with that of Hst2, a Sir2 Ib gene from S. cerevisiae. Three exons and
      two introns were identified within the 1472-bp SsSir2 genomic DNA sequence of S.
      schenckii. A three-dimensional model of SsSir2 was constructed using a homology
      modeling method, and its reliability was evaluated. The active site of SsSir2 was
      identified by docking simulation, which indicated that several important
      residues, such as Asn127 and Asp129, play an important role in the histone
      deacetylase activity of Sir2 family proteins. The differential expression of the
      SsSir2 in two stages was demonstrated by real-time RT-PCR. The expression of
      SsSir2 was higher in the yeast stage compared with that in the mycelial one,
      which indicated that SsSir2 may be involved in the phenotypic switching and
      morphogenesis of the yeast phase in S. schenckii.

PMID- 24682410
TI  - Protein kinase C-delta mediates sepsis-induced activation of complement 5a and
      urokinase-type plasminogen activator signaling in macrophages.
AB  - OBJECTIVE AND DESIGN: Activations of the complement C5a (C5a) and the urokinase
      type plasminogen activator (uPA) are commonly seen together during sepsis.
      However, the mechanism linking these two important pathways remains elusive.
      MATERIAL, METHODS AND TREATMENT: We used the C57BL/6 J mice model of sepsis
      induced by cecal ligation puncture (CLP) procedure, injected anti-C5aR or
      rottlerin through the tail vein to neutralize C5aR or PKC-delta, and then
      isolated peritoneal macrophages. Total RNA was isolated from the cells and
      analyzed by quantitative PCR. RESULTS: Our study revealed that neutralizing C5aR
      markedly inhibited sepsis-induced uPA receptor (uPAR) expression and its
      downstream signaling in macrophage. Similarly, neutralizing uPAR suppressed
      sepsis activation of C5a signaling. Importantly, inhibition of PKC-delta largely
      blocked sepsis-induced expression of C5aR and uPAR. CONCLUSIONS: Our study
      demonstrates a crosstalk between the complement C5a signaling and the
      fibrinolytic uPA pathways, which may depend on each other to maintain their
      expression and signaling, and reveals a central role of PKC-delta in mediating
      sepsis-induced activation of these pathways.

PMID- 24682411
TI  - Regulated expression of leukocyte-specific transcript (LST) 1 in human intestinal
      inflammation.
AB  - INTRODUCTION: Leukocyte-specific transcript 1 (LST1) encoded peptides are
      involved in immunomodulation and nanotube-mediated cell-cell communication. The
      aim of this study was to assess the expression of LST1 in colonic epithelium and
      endothelium during intestinal inflammation. METHODS: LST1 expression was
      evaluated by RT-PCR, FACS, western blot analysis, and immunohistochemistry in
      intestinal epithelial Caco-2 cells, human intestinal microvascular endothelial
      cells and in human histological specimens from inflammatory bowel disease (IBD)
      patients and non-IBD colitis patients. RESULTS: LST1 expression was significantly
      increased upon proinflammatory stimulation in intestinal epithelial and
      endothelial cells. Furthermore, LST1 tissue expression was significantly enhanced
      in macroscopically inflamed colonic mucosal biopsies as compared to non-affected
      mucosal areas. CONCLUSIONS: This is the first report demonstrating regulated LST1
      expression in human intestinal epithelial and microvascular endothelial cells and
      in inflamed colonic tissue from IBD patients. Proinflammatory expression of LST1
      occurs in the setting of human IBD and is not restricted to immune cell
      populations. Future studies are needed to further elucidate the role of soluble
      and membrane-expressed LST1 in the regulation of mucosal intestinal immunity and
      inflammation as well as to reveal possible therapeutic implications.

PMID- 24682412
TI  - Analysis and visualization of complex macroevolutionary dynamics: an example from
      Australian scincid lizards.
AB  - The correlation between species diversification and morphological evolution has
      long been of interest in evolutionary biology. We investigated the relationship
      between these processes during the radiation of 250+scincid lizards that
      constitute Australia's most species-rich clade of terrestrial vertebrates. We
      generated a time-calibrated phylogenetic tree for the group that was more than
      85% complete at the species level and collected multivariate morphometric data
      for 183 species. We reconstructed the dynamics of species diversification and
      trait evolution using a Bayesian statistical framework (BAMM) that simultaneously
      accounts for variation in evolutionary rates through time and among lineages. We
      extended the BAMM model to accommodate time-dependent phenotypic evolution, and
      we describe several new methods for summarizing and visualizing macroevolutionary
      rate heterogeneity on phylogenetic trees. Two major clades (Lerista, Ctenotus;
      >90 spp. each) are associated with high rates of species diversification relative
      to the background rate across Australian sphenomorphine skinks. The Lerista clade
      is characterized by relatively high lability of body form and has undergone
      repeated instances of limb reduction, but Ctenotus is characterized by an extreme
      deceleration in the rate of body shape evolution. We estimate that rates of
      phenotypic evolution decreased by more than an order of magnitude in the common
      ancestor of the Ctenotus clade. These results provide evidence for a modal shift
      in phenotypic evolutionary dynamics and demonstrate that major axes of
      morphological variation can be decoupled from species diversification. More
      generally, the Bayesian framework described here can be used to identify and
      characterize complex mixtures of dynamic processes on phylogenetic trees.
      [Bayesian; diversification; evolvability; lizard; macroevolution, punctuated
      equilibrium, speciation.].

PMID- 24682413
TI  - A preliminary framework for DNA barcoding, incorporating the multispecies
      coalescent.

PMID- 24682414
TI  - Ribosomal DNA sequence heterogeneity reflects intraspecies phylogenies and
      predicts genome structure in two contrasting yeast species.
AB  - The ribosomal RNA encapsulates a wealth of evolutionary information, including
      genetic variation that can be used to discriminate between organisms at a wide
      range of taxonomic levels. For example, the prokaryotic 16S rDNA sequence is very
      widely used both in phylogenetic studies and as a marker in metagenomic surveys
      and the internal transcribed spacer region, frequently used in plant
      phylogenetics, is now recognized as a fungal DNA barcode. However, this
      widespread use does not escape criticism, principally due to issues such as
      difficulties in classification of paralogous versus orthologous rDNA units and
      intragenomic variation, both of which may be significant barriers to accurate
      phylogenetic inference. We recently analyzed data sets from the Saccharomyces
      Genome Resequencing Project, characterizing rDNA sequence variation within
      multiple strains of the baker's yeast Saccharomyces cerevisiae and its nearest
      wild relative Saccharomyces paradoxus in unprecedented detail. Notably, both
      species possess single locus rDNA systems. Here, we use these new variation
      datasets to assess whether a more detailed characterization of the rDNA locus can
      alleviate the second of these phylogenetic issues, sequence heterogeneity, while
      controlling for the first. We demonstrate that a strong phylogenetic signal
      exists within both datasets and illustrate how they can be used, with existing
      methodology, to estimate intraspecies phylogenies of yeast strains consistent
      with those derived from whole-genome approaches. We also describe the use of
      partial Single Nucleotide Polymorphisms, a type of sequence variation found only
      in repetitive genomic regions, in identifying key evolutionary features such as
      genome hybridization events and show their consistency with whole-genome
      Structure analyses. We conclude that our approach can transform rDNA sequence
      heterogeneity from a problem to a useful source of evolutionary information,
      enabling the estimation of highly accurate phylogenies of closely related
      organisms, and discuss how it could be extended to future studies of multilocus
      rDNA systems. [concerted evolution; genome hydridisation; phylogenetic analysis;
      ribosomal DNA; whole genome sequencing; yeast]. 

PMID- 24682415
TI  - Reply to: doi:10.1007/s00464-013-3395-4: Re: "Laparoscopic bile duct exploration
      via choledochotomy followed by primary duct closure is feasible and safe..."
      (2013 (27):4164-4170).

PMID- 24682417
TI  - Molecular pathways: preclinical models and clinical trials with metformin in
      breast cancer.
AB  - Metformin, an oral biguanide widely used to treat diabetes, has considerable
      potential and is in clinical trials as an experimental preventive or therapeutic
      agent for a range of cancers. Direct actions targeting cellular pathways,
      particularly via AMP-activated protein kinase and through inhibiting
      mitochondrial ATP synthesis, or systemic mechanisms involving insulin and insulin
      like growth factors have been much studied in vitro and in preclinical models.
      Epidemiologic and retrospective studies also provide clinical evidence in support
      of metformin as an antitumor agent. Preoperative window-of-opportunity trials
      confirm the safety of metformin in women with primary breast cancer, and
      demonstrate reduction in tumor cell proliferation and complex pathways of gene
      suppression or overexpression attributable to metformin. Confirmation of insulin
      mediated effects, independent of body mass index, also supports the potential
      benefit of adjuvant metformin therapy. Neoadjuvant, adjuvant, and advanced
      disease trials combining metformin with established anticancer agents are under
      way or proposed. Companion biomarker studies will utilize in vitro and
      preclinical understanding of the relevant molecular pathways to, in future,
      refine patient and tumor selection for metformin therapy.

PMID- 24682418
TI  - Steroidogenic germline polymorphism predictors of prostate cancer progression in
      the estradiol pathway.
AB  - PURPOSE: Reliable biomarkers that predict prostate cancer outcomes are urgently
      needed to improve and personalize treatment approaches. With this goal in mind,
      we individually and collectively appraised common genetic polymorphisms related
      to estradiol metabolic pathways to find prostate cancer prognostic markers.
      METHODS: The genetic profiles of 526 men with organ-confined prostate cancer were
      examined to find common genetic polymorphisms related to estradiol metabolic
      pathways and these findings were replicated in a cohort of 213 men with more
      advanced disease (follow-up time for both cohorts, >7.4 years). Specifically, we
      examined 71 single-nucleotide polymorphisms (SNP) in SULT2A1, SULT2B1, CYP1B1,
      COMT, CYP3A4, CYP3A5, CYP3A43, NQO1, and NQO2 and assessed the impact of the SNPs
      alone and in combination on prostate cancer progression and on circulating
      hormone levels. RESULTS: According to a multivariate analysis, CYP1B1
      (rs1800440), COMT (rs16982844), and SULT2B1 (rs12460535, rs2665582, rs10426628)
      were significantly associated with prostate cancer progression and hormone
      levels. Remarkably, by combining the SNP information with previously identified
      HSD17B2 markers, the patients could be stratified into four distinct prognostic
      subgroups. The most prominent association was observed for the eight-marker
      combination [CYP1B1 (rs1800440), SULT2B1 (rs12460535, rs2665582, and rs10426628),
      and HSD17B2 (rs4243229, rs1364287, rs2955162, and rs1119933)]. CONCLUSION: This
      study identified specific germline variations in estradiol metabolism-related
      pathways, namely CYP1B1, SULT2B1, and HSD17B2, as novel prognostic markers that
      are cumulatively associated with increased risk of prostate cancer progression.
      This panel of markers warrants additional investigation and validation to help
      stratify patients according to their risk of progression. Clin Cancer Res;
      20(11); 2971-83. (c)2014 AACR.

PMID- 24682419
TI  - Visual scanning behaviours and their role in the navigation of the Australian
      desert ant Melophorus bagoti.
AB  - Ants are excellent navigators, using a combination of innate strategies and
      learnt information to guide habitual routes. The mechanisms underlying this
      behaviour are little understood though one avenue of investigation is to explore
      how innate sensori-motor routines are used to accomplish route navigation. For
      instance, Australian desert ant foragers are occasionally observed to cease
      translation and rotate on the spot. Here, we investigate this behaviour using
      high-speed videography and computational analysis. We find that scanning
      behaviour is saccadic with pauses separated by fast rotations. Further, we have
      identified four situations where scanning is typically displayed: (1) by naive
      ants on their first departure from the nest; (2) by experienced ants departing
      from the nest for their first foraging trip of the day; (3) by experienced ants
      when the familiar visual surround was experimentally modified, in which case
      frequency and duration of scans were proportional to the degree of modification;
      (4) when the information from visual cues is at odds with the direction indicated
      by the ant's path integration system. Taken together, we see a general
      relationship between scanning behaviours and periods of uncertainty. 

PMID- 24682420
TI  - Suppression of allergic and inflammatory responses by essential oils derived from
      herbal plants and citrus fruits.
AB  - The aim of the present study was to investigate the biological activity of 20
      essential oils (EOs) derived from herbal plants and citrus fruits. The in vitro
      anti-allergic and anti-inflammatory activities of these oils were investigated,
      and the EO which was found to have the strongest activity of the 20 EOs examined,
      was investigated further to identify its components and bioactive compounds. The
      in vitro anti-allergic activity was determined by measuring the release of beta
      hexosaminidase from rat basophilic leukemia (RBL-2H3) cells treated with the
      calcium ionophore, A23187. The in vitro anti-inflammatory activity was determined
      by measuring the production of tumor necrosis factor-alpha (TNF-alpha) in
      RAW264.7 murine macrophages treated with lipopolysaccharide. Among the EOs
      examined, lemongrass [Cymbopogon citratus (DC.) Stapf] elicited the strongest
      anti-allergic and anti-inflammatory effects. A principal component of this EO is
      citral (3,7-dimethyl-2,6-octadien-1-al) (74.5%), a mixture of the stereoisomers,
      geranial (trans-citral, 40.16%) and neral (cis-citral, 34.24%), as determined by
      chromatography-mass spectrometry analysis. The activities of citral and geranial
      are similar to those of lemongrass EO. These compounds elicited significant in
      vivo anti-allergic and anti-inflammatory effects, suppressing an immunoglobulin E
      (IgE)-induced passive cutaneous anaphylactic reaction in mice and a 12-O
      tetradecanoylphorbol-13-acetate-induced inflammatory mouse ear edema,
      respectively. Our data demonstrate that lemongrass EO and its constituents,
      citral and geranial, may be a therapeutic candidate for allergic and inflammatory
      diseases.

PMID- 24682421
TI  - Clofarabine in combination with a standard remission induction regimen (cytosine
      arabinoside and idarubicin) in patients with previously untreated intermediate
      and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic
      syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia
      groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial).
AB  - This study aims to determine the maximum tolerated dose (MTD) of clofarabine
      combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine
      arabinoside) in adults with untreated acute myelogenous leukemia or high-risk
      myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56
      years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection
      (arm B) at the dose level of 5 * 10 or 5 * 15 mg/m(2)/day in an algorithmic dose
      escalation 3 + 3 design. A consolidation course (intermediate dose cytosine
      arabinoside, idarubicin) was planned for patients in complete remission (CR).
      Primary endpoint was safety and tolerance as measured by dose limiting toxicity
      (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and
      hematological recovery after induction and consolidation. Five DLTs were observed
      (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT
      at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to
      adverse events not classified as DLT. Prolonged hypoplasia was observed in five
      patients. CR + complete remission with incomplete recovery were achieved in 21
      patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %)
      receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 * 10 mg/m(2)/day, resulted
      in one DLT and no early treatment withdrawals. MTD of clofarabine combined with
      cytosine arabinoside and idarubicin is 5 * 10 mg/m(2)/day. 

PMID- 24682422
TI  - Mechanisms of endothelium-dependent relaxation evoked by anandamide in isolated
      human pulmonary arteries.
AB  - Endocannabinoids contract, relax or do not affect vessels with different calibre
      and tone in the pulmonary circulation in four species. The aim of the present
      study was to determine the mechanisms involved in the anandamide-induced
      relaxation of human pulmonary arteries (hPAs). Studies were performed in the
      isolated hPAs pre-constricted with the prostanoid TP receptor agonist, U-46619.
      To detect fatty acid amide hydrolase (FAAH) expression, Western blots were used.
      Anandamide concentration dependently relaxed the endothelium-intact hPAs pre
      constricted with U-46619. The anandamide-induced relaxation was virtually
      abolished by removal of the endothelium and strongly attenuated by inhibitors of
      cyclooxygenases (indomethacin, COX-1/COX-2, and nimesulide, COX-2), nitric oxide
      synthase (N (G) -nitro-L-arginine methyl ester) given separately or in
      combination, FAAH (URB597), and the prostanoid IP receptor antagonist, RO1138452.
      The anandamide-evoked relaxation in the endothelium-intact vessels was attenuated
      in KCl pre-constricted preparations or by the inhibitor of large-conductance
      Ca(2+)-activated K(+) channels, iberiotoxin. In experiments performed in the
      presence of URB597 to exclude effects of anandamide metabolites, the antagonist
      of the endothelial cannabinoid receptor, O-1918, diminished the anandamide-evoked
      relaxation whereas the antagonists of cannabinoid CB1, CB2 and vanilloid TRPV1
      receptors, AM251, SR144528 and capsazepine, respectively, had no effect. Western
      blot studies revealed the occurrence of FAAH protein in the hPAs. The present
      study shows that anandamide breakdown products, cyclooxygenase pathways, nitric
      oxide, potassium channels and the O-1918-sensitive cannabinoid receptor play a
      role in the anandamide-induced relaxation of the hPAs with intact endothelium.

PMID- 24682423
TI  - Isoenzyme-specific regulation of cardiac Kv1.5/Kvbeta1.2 ion channel complex by
      protein kinase C: central role of PKCbetaII.
AB  - The ultrarapidly activating delayed rectifier current, I(Kur), is a main
      determinant of atrial repolarization in humans. I(Kur) and the underlying ion
      channel complex Kv1.5/Kvbeta1.2 are negatively regulated by protein kinase C.
      However, the exact mode of action is only incompletely understood. We therefore
      analyzed isoenzyme-specific regulation of the Kv1.5/Kvbeta1.2 ion channel complex
      by PKC. Cloned ion channel subunits were heterologously expressed in Xenopus
      oocytes, and measurements were performed using the double-electrode voltage-clamp
      technique. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) resulted
      in a strong reduction of Kv1.5/Kvbeta1.2 current. This effect could be prevented
      using the PKC inhibitor staurosporine. Using the bisindolylmaleimide Ro-31-8220
      as an inhibitor and ingenol as an activator of the conventional PKC isoforms, we
      were able to show that the Kv1.5/Kvbeta1.2 ion channel complex is mainly
      regulated by conventional isoforms. Whereas pharmacological inhibition of
      PKCalpha with HBDDE did not attenuate the PMA-induced effect, current reduction
      could be prevented using inhibitors of PKCbeta. Here, we show the isoform betaII
      plays a central role in the PKC-dependent regulation of Kv1.5/Kvbeta1.2 channels.
      These results add to the current understanding of isoenzyme-selective regulation
      of cardiac ion channels by protein kinases.

PMID- 24682424
TI  - Major incidents.

PMID- 24682427
TI  - Radiology in the Nazi era: part 1. The state, citizens, and marginalization:
      normality in the Nazi state.

PMID- 24682426
TI  - Culture-sensitive adaptation and validation of the community-oriented program for
      the control of rheumatic diseases methodology for rheumatic disease in Latin
      American indigenous populations.
AB  - The purpose of the study is to validate a culturally sensitive adaptation of the
      community-oriented program for the control of rheumatic diseases (COPCORD)
      methodology in several Latin American indigenous populations. The COPCORD Spanish
      questionnaire was translated and back-translated into seven indigenous languages:
      Warao, Karina and Chaima (Venezuela), Mixteco, Maya-Yucateco and Raramuri
      (Mexico) and Qom (Argentina). The questionnaire was administered to almost 100
      subjects in each community with the assistance of bilingual translators.
      Individuals with pain, stiffness or swelling in any part of the body in the
      previous 7 days and/or at any point in life were evaluated by physicians to
      confirm a diagnosis according to criteria for rheumatic diseases. Overall,
      individuals did not understand the use of a 0-10 visual analog scale for pain
      intensity and severity grading and preferred a Likert scale comprising four items
      for pain intensity (no pain, minimal pain, strong pain, and intense pain). They
      were unable to discriminate between pain intensity and pain severity, so only
      pain intensity was included. For validation, 702 subjects (286 male, 416 female,
      mean age 42.7 +/- 18.3 years) were interviewed in their own language. In the last
      7 days, 198 (28.2 %) subjects reported having musculoskeletal pain, and 90 (45.4
      %) of these had intense pain. Compared with the physician-confirmed diagnosis,
      the COPCORD questionnaire had 73.8 % sensitivity, 72.9 % specificity, a positive
      likelihood ratio of 2.7 and area under the receiver operating characteristic
      curve of 0.73. The COPCORD questionnaire is a valid screening tool for rheumatic
      diseases in indigenous Latin American populations.

PMID- 24682425
TI  - Metal/metalloid stress tolerance in plants: role of ascorbate, its redox couple,
      and associated enzymes.
AB  - The enhanced generation of reactive oxygen species (ROS) under metal/metalloid
      stress is most common in plants, and the elevated ROS must be successfully
      metabolized in order to maintain plant growth, development, and productivity.
      Ascorbate (AsA) is a highly abundant metabolite and a water-soluble antioxidant,
      which besides positively influencing various aspects in plants acts also as an
      enigmatic component of plant defense armory. As a significant component of the
      ascorbate-glutathione (AsA-GSH) pathway, it performs multiple vital functions in
      plants including growth and development by either directly or indirectly
      metabolizing ROS and its products. Enzymes such as monodehydroascorbate reductase
      (MDHAR, EC 1.6.5.4) and dehydroascorbate reductase (DHAR, EC 1.8.5.1) maintain
      the reduced form of AsA pool besides metabolically controlling the ratio of AsA
      with its oxidized form (dehydroascorbate, DHA). Ascorbate peroxidase (APX, EC
      1.11.1.11) utilizes the reduced AsA pool as the specific electron donor during
      ROS metabolism. Thus, AsA, its redox couple (AsA/DHA), and related enzymes
      (MDHAR, DHAR, and APX) cumulatively form an AsA redox system to efficiently
      protect plants particularly against potential anomalies caused by ROS and its
      products. Here we present a critical assessment of the recent research reports
      available on metal/metalloid-accrued modulation of reduced AsA pool, AsA/DHA
      redox couple and AsA-related major enzymes, and the cumulative significance of
      these antioxidant system components in plant metal/metalloid stress tolerance. 

PMID- 24682428
TI  - Understanding balance differences in individuals with multiple sclerosis with
      mild disability: an investigation of differences in sensory feedback on postural
      control during a Romberg task.
AB  - A major presenting symptom in 'individuals with multiple sclerosis with mild
      balance disability' (IwMS) is poor postural control, resulting from slowed spinal
      somatosensory conduction. Postural control deficits in IwMS are most apparent
      when vision is removed and the base of support is reduced such is the case during
      tandem and single support stances. The current study used center of pressure
      (COP) measurements to determine whether postural control differences exist
      between IwMS and either 'healthy age-matched individuals' (HAMI) or 'community
      dwelling older adults' (OA). Postural control was evaluated using a Romberg
      standing task, which required participants to stand with their feet together and
      hands by their sides for 45 s with either their eyes open or closed. Results
      revealed that COP velocity root mean square was greater in IwMS and their COP
      position was closer to their self-selected maximum stability limits (e.g.,
      greater Standing Index proportion) when vision was removed compared to HAMI.
      Conversely, IwMS displayed similar postural control characteristics to OA. The
      current study highlights two novel findings: (1) the utility of novel COP
      measurements to assess differences in the level of postural control in IwMS; and
      (2) the benefit of assessing postural control levels in IwMS to not only a
      population with a fully intact and functional postural control system (HAMI) but
      also to another population that is thought to experience postural control
      deficits (OA).

PMID- 24682429
TI  - Dissociation between the impact of evidence on eye movement target choice and
      confidence judgements.
AB  - It has been suggested that the evidence used to support a decision to move our
      eyes and the confidence we have in that decision are derived from a common
      source. Alternatively, confidence may be based on further post-decisional
      processes. In three experiments, we examined this. In Experiment 1, participants
      chose between two targets on the basis of varying levels of evidence (i.e., the
      direction of motion coherence in a random dot kinematogram). They indicated this
      choice by making a saccade to one of two targets and then indicated their
      confidence. Saccade trajectory deviation was taken as a measure of the inhibition
      of the non-selected target. We found that as evidence increased so did confidence
      and deviations of saccade trajectory away from the non-selected target. However,
      a correlational analysis suggested they were not related. In Experiment 2, an
      option to opt-out of the choice was offered on some trials if choice proved too
      difficult. In this way, we isolated trials on which confidence in target
      selection was high (i.e., when the option to opt-out was available but not
      taken). Again saccade trajectory deviations were found not to differ in relation
      to confidence. In Experiment 3, we directly manipulated confidence, such that
      participants had high or low task confidence. They showed no differences in
      saccade trajectory deviations. These results support post-decisional accounts of
      confidence: evidence supporting the decision to move the eyes is reflected in
      saccade control, but the confidence that we have in that choice is subject to
      further post-decisional processes. 

PMID- 24682435
TI  - GABAB receptors are expressed in human aortic smooth muscle cells and regulate
      the intracellular Ca(2+) concentration.
AB  - The aim of this study was to investigate the expression of GABAB receptors, a
      subclass of receptors to the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABAB), in human aortic smooth muscle cells (HASMCs), and to explore if altering
      receptor activation modified intracellular Ca(2+) concentration ([Ca(2+)]i) of
      HASMCs. Real-time PCR, western blots and immunofluorescence were used to
      determine the expression of GABABR1 and GABABR2 in cultured HASMCs.
      Immunohistochemistry was used to localize the two subunits in human left anterior
      descending artery (LAD). The effects of the GABAB receptor agonist baclofen on
      [Ca(2+)]i in cultured HASMCs were demonstrated using fluo-3. Both GABABR1 and
      GABABR2 mRNA and protein were identified in cultured HASMCs and antibody staining
      was also localized to smooth muscle cells of human LAD. 100 MUM baclofen caused a
      transient increase of [Ca(2+)]i in cultured HASMCs regardless of whether Ca(2+)
      was added to the medium, and the effects were inhibited by pre-treatment with
      CGP46381 (selective GABAB receptor antagonist), pertussis toxin (a Gi/o protein
      inhibitor), and U73122 (a phospholipase C blocker). GABAB receptors are expressed
      in HASMCs and regulate the [Ca(2+)]i via a Gi/o-coupled receptor pathway and a
      phospholipase C activation pathway. 

PMID- 24682434
TI  - HLA class I, KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV
      vaccine clinical trial.
AB  - RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy.
      This study consisted of more than 8,000 individuals in each arm of the trial,
      representing the four major regions of Thailand. Human leukocyte antigen (HLA)
      class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96
      genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV
      1-uninfected individuals to identify the immunogenetic diversity and population
      structure of this cohort. High-resolution genotyping identified the common HLA
      alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01,
      B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04,
      C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype
      was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present
      in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies
      greater than 90 %. The combined HLA and KIR profile suggests admixture with
      neighboring Asian populations. Principal component and correspondence analyses
      comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3)
      populations using AIMs corroborated these findings. Structure analyses identified
      a distinct profile in the Thai population that did not match the Asian or other
      HapMap3 samples. This shows genetic variability unique to Thais in RV144, making
      it essential to take into account population stratification while performing
      genetic association studies. The overall analyses from all three genetic markers
      indicate that the RV144 samples are representative of the Thai population. This
      will inform subsequent host genetic analyses in the RV144 cohort and provide
      insight for future genetic association studies in the Thai population. 

PMID- 24682436
TI  - Triple versus dual antiplatelet therapy after percutaneous coronary intervention
      for coronary bifurcation lesions: results from the COBIS (COronary BIfurcation
      Stent) II Registry.
AB  - The efficacy and safety of adding cilostazol to aspirin plus clopidogrel (triple
      antiplatelet therapy, TAPT) have not been fully evaluated in complex percutaneous
      coronary intervention (PCI). We sought to investigate whether TAPT after PCI for
      bifurcation lesions improves long-term clinical outcomes. Consecutive patients
      undergoing PCI for bifurcation lesions were enrolled from 18 centers in Korea
      between 2003 and 2009. We compared target vessel failure (TVF), defined as a
      composite of cardiac death, myocardial infarction (MI), and target vessel
      revascularization (TVR), among 675 patients who received TAPT and 2081 who
      received dual antiplatelet therapy (DAPT: aspirin plus clopidogrel). Patients who
      received TAPT had more cardiovascular co-morbidities with regard to clinical,
      angiographic, and procedural characteristics. During the follow-up (median 36
      months), 346 (12.6%) TVFs occurred. The incidence of TVF was significantly higher
      in the TAPT group, mainly driven by a higher TVR rate. In the TAPT group,
      however, the risk of TVF was not significantly different from the DAPT group
      after adjusting for the confounders of TVFs (adjusted hazard ratio [HR] 0.86, 95%
      confidence interval [CI] 0.53-1.39, p = 0.53). And also, there were no
      significant differences between the 2 groups in terms of the risks for death,
      cardiac death, MI, TVR, stent thrombosis, or cerebrovascular accident. These
      results were consistent after propensity score-matched analysis, and were also
      constant among the high-risk subgroups. TAPT after bifurcation PCI had no
      beneficial effect on the risk of long-term clinical outcomes in real-world
      clinical practice. Further studies are needed to confirm these findings.

PMID- 24682439
TI  - Biologic therapy response and drug survival for females compared to males with
      rheumatoid arthritis: a cohort study.
AB  - Prior research has identified differences between sexes in rheumatoid arthritis
      (RA) disease characteristics and treatment response, but not how these
      differences affect therapeutic decision making to switch therapy. Our objective
      was to assess for sex differences in RA disease activity during the course of
      biologic therapy and how these differences impact drug survival and therapeutic
      switching. Data from the Alberta Biologics Pharmacosurveillance Program, a
      population-based observational cohort of patients receiving biologic therapy for
      RA, were used for a sex-stratified analysis of disease activity. Linear mixed
      model analysis was applied to compare continuous effectiveness outcomes (DAS28,
      HAQ scores, visual analogue scales of patient-reported outcomes). Chi-squared
      tests and log-rank tests were used to determine differences in the frequency of
      switching and drug survival between females and males. At biologic initiation,
      females (n = 419) and males (n = 148) had similar disease activity (DAS28 in
      females 5.83, males 5.72), but females reported worse function (HAQ 1.64 vs 1.51,
      p = 0.037) and more fatigue (6.7 vs 5.9/10, p = 0.013), but the same global score
      as males (6.9 vs 6.8/10). During biologic therapy, females reported more fatigue
      (beta = -0.454, 95 % CI -0.852, -0.056, p = 0.0252), worse function (beta = 
      0.183, 95 % CI -0.291, -0.074, p = 0.0010) and higher DAS28 scores (beta = 
      0.401, 95 % CI -0.617, -0.184, p = 0.0003). A new composite disease activity
      index, the HUPI, eliminated the observed differences in disease activity scores
      between females and males. Median survival for biologic-naive patients was
      similar between sexes (3.7 years males, 3.3 years females, log-rank test p =
      0.25). The frequency of switching and survival on subsequent biologics were the
      same between females and males. Guided by traditional outcome measurement tools,
      worse disease activity and patient-reported outcomes through the course of
      therapy did not translate into differences in drug survival or more frequent
      switching for females on biologic therapy for RA.

PMID- 24682440
TI  - Congenital nephrotic syndrome and recurrence of proteinuria after renal
      transplantation.
AB  - Renal transplantation (RTx) is the only curative treatment for most cases of
      congenital and infantile nephrotic syndrome (NS) caused by genetic defects in
      glomerular podocyte proteins. The outcome of RTx in these children is usually
      excellent, with no recurrence of nephrotic syndrome. A subgroup of patients with
      the Finnish type of congenital nephrosis (CNF), shows, however, a clear risk for
      post-RTx proteinuria. Most of these patients have a homozygous truncating
      mutation (Fin-major mutation) in the nephrin gene (NPHS1), leading to total
      absence of the major podocyte protein, nephrin. After RTx, these patients develop
      anti-nephrin antibodies resulting in nephrotic range proteinuria. Plasma exchange
      combined with cyclophosphamide and anti-CD20 antibodies has proved to be
      successful therapy for these episodes. NS recurrence has also occurred in a few
      patients with mutations in the podocin gene (NPHS2). No anti-podocin antibodies
      have been detectable, and the pathophysiology of the recurrence remains open.
      While most of these episodes have resolved, the optimal therapy remains to be
      determined.

PMID- 24682442
TI  - Nipple-areolar complex ischemia after nipple-sparing mastectomy with immediate
      implant-based reconstruction: risk factors and the success of conservative
      treatment.
AB  - BACKGROUND: Nipple-sparing mastectomy performed via an inframammary fold incision
      with implant-based reconstruction is an oncologically safe procedure that
      provides excellent cosmesis. OBJECTIVES: The authors report their experience with
      conservative treatment of postoperative nipple-areolar complex (NAC) ischemia and
      an analysis of risk factors for NAC ischemia and conservative treatment failure.
      METHODS: A retrospective chart review was conducted of 318 nipple-sparing
      mastectomies performed through inframammary fold incisions with implant-based
      reconstruction between July 2006 and October 2012. NAC dressings consisted of
      topical nitroglycerin, external warming for 24 hours, antibacterial petrolatum
      gauze, and a loose bra for 1 week. Patients were monitored for NAC ischemia as
      the primary endpoint. NAC ischemia was treated with bacitracin ointment. In cases
      of full-thickness ischemia, expanders were also partially deflated. RESULTS:
      Partial- and full-thickness NAC ischemia occurred in 44 (13.8%) and 21 (6.6%)
      cases, respectively. All partial- and 17 full-thickness cases resolved with
      conservative treatment. Of these, 7 partial- and 2 full-thickness cases suffered
      residual depigmentation. Four full-thickness cases required operative
      debridement. Factors associated with NAC ischemia included increasing age (P =
      .035), higher body mass index (P = .0009), greater breast volume (P = .0023), and
      diabetes (P = .0046). Factors associated with conservative treatment failure
      included increasing age (P < .0001), higher body mass index (P = .014), greater
      breast volume (P = .020), smoking (P = .0449), acellular dermal matrix use (P <
      .0001), and single-stage reconstruction (P = .0090). CONCLUSIONS: Postoperative
      NAC ischemia can be effectively managed conservatively to preserve cosmesis and
      implant viability. Knowledge of risk factors for NAC ischemia and conservative
      treatment failure may improve future patient counseling and outcomes.

PMID- 24682443
TI  - Rhinoplasty: the lateral crura-alar ring.
AB  - BACKGROUND: Rhinoplasty surgeons routinely excise or incise the lateral crura
      despite nostril rim retraction, bossa, and collapse. Given recent emphasis on
      preserving the lateral crura, a review of the lateral crura's anatomy is
      warranted. OBJECTIVES: The authors quantify specific anatomical aspects of the
      lateral crura in cadavers and clinical patients. METHODS: This was a 2-part
      investigation, consisting of a prospective clinical measurement study of 40
      consecutive rhinoplasty patients (all women) and 20 fresh cadaver dissections (13
      males, 1 female). In the clinical phase, the alar cartilages were photographed
      intraoperatively and alar position (ie, orientation), axis, and width were
      measured. Cadaver dissections concentrated on parts of the lateral crura (alar
      cartilages and alar ring) that were inaccessible clinically. RESULTS: Average
      clinical patient age was 28 years (range, 14-51 years). Average cadaver age was
      74 (range, 57-88 years). Clinically, the distance of the lateral crura from the
      mid-nostril point averaged 5.9 mm, and the cephalic orientation averaged 43.6
      degrees. The most frequent configuration of the axis was smooth-straight in the
      horizontal axis and a cephalic border higher than the caudal border in the
      vertical axis. Maximal lateral crura width averaged 10.1 mm. In the cadavers,
      average lateral crural dimensions were 23.4 mm long, 6.4 mm wide at the domal
      notch, 11.1 mm wide at the so-designated turning point (TP), and 0.5 mm
      thickness. The accessory cartilage chain was present in all dissections.
      CONCLUSIONS: The lateral crura-alar ring was present in all dissections as a
      circular ring continuing around toward the anterior nasal spine but not abutting
      the pyriform. The lateral crura (1) begins at the domal notch and ends at the
      accessory cartilages, (2) exhibits a distinct TP from the caudal border, (3) has
      distinct horizontal and vertical vectors, and (4) should have a caudal border
      higher than the cephalic border. Alar malposition may be associated with
      position, orientation, or configuration.

PMID- 24682444
TI  - MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell
      proliferation by directly targeting HMGA2.
AB  - MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNA
      molecules which can act as oncogenes or tumor suppressor genes in human cancer.
      However, the possible functions and mechanisms of miRNA action in gallbladder
      cancer (GBC) have not been elucidated. In the present study, it was found that
      miR-26a was often downregulated in GBC and the expression of miR-26a was
      associated with neoplasm histological grade. miR-26a significantly inhibited the
      proliferation of GBC cells based on the gain-of-function assays. Furthermore, we
      demonstrated that high mobility group AT-hook 2 (HMGA2) was a direct target of
      miR-26a. The results showed that HMGA2 mRNA levels and miR-26a levels were
      negatively correlated. In addition, we confirmed that reintroduction of HMGA2
      antagonized the inhibition of miR-26a to GBC cell proliferation and all these
      effects were achieved through the cell cycle. Together, all these results suggest
      that miR-26a expression contributes to GBC proliferation by targeting HMGA2. miR
      26a shows promise as a prognosis factor and therapeutic target of GBC patients. 

PMID- 24682445
TI  - Radiation protection from whole-body gamma irradiation (6.7 Gy): behavioural
      effects and brain protein-level changes by an aminothiol compound GL2011 in the
      Wistar rat.
AB  - GL2011 is a naturally occurring thiol compound and a series of thiol compounds
      have been proposed as radioprotectors. Radioprotective efficacy of a triple
      intraperitoneal dose of GL2011 of 100 mg/kg body weight of Wistar rats, 30 min
      prior to and 3 and 6 h following irradiation (6.7 Gy) was evaluated. Four groups
      of animals were used, vehicle-treated non-irradiated (VN), GL2011-treated and
      irradiated (GI), GL2011-treated and non-irradiated (GN) and vehicle-treated and
      irradiated (VI) (n = 30 per group). The radioprotective efficacy of GL2011 was
      determined by measuring 28-day survival and intestinal crypt cell survival.
      Neuroprotection in terms of behaviour was evaluated using the behavioural
      observational battery, open field test and elevated plus maze paradigm. An RNA
      microarray was carried out in order to show differences at the RNA level between
      VI and VN groups. Brain protein changes were identified using a gel-based
      proteomics method and major brain receptor complex levels were determined by blue
      native gels followed by immunoblotting. 28-Day survival rate in VI was 30 %, in
      GI survival was 93 %, survival of VN and GN was 100 %. Jejunal crypt cell
      survival was significantly enhanced in GI. Protein-level changes of peroxiredoxin
      5, Mn-superoxide dismutase 2, voltage-dependent anion-selective channel protein
      1, septin 5 and dopamine D2 receptor complex levels were paralleling radiation
      damage and protection. Taken together, the findings demonstrate that GL2011
      improves survival rates and jejunal crypt survival, provides partial
      neuroprotection at the behavioural level and modulates proteins known to be
      involved in protection against oxidative stress-mediated cell damage.

PMID- 24682446
TI  - A beta-glucosidase from Novosphingobium sp. GX9 with high catalytic efficiency
      toward isoflavonoid glycoside hydrolysis and (+)-catechin transglycosylation.
AB  - In view of the important role of isoflavonoids and their related glycoconjugates
      in human health, there is considerable interest in their enzymatic conversion.
      SBGL, a novel beta-glucosidase isolated from Novosphingobium sp. GX9, was
      expressed in Escherichia coli and found to have high activity for hydrolysis of
      daidzin and genistin. SBGL showed very low K m values for daidzin and genistin,
      and the k cat/K m values for these substrates were 33,300 and 19,200 s(-1) mM(
      1), respectively. The SBGL glucosidase could also transglycosylate the flavanol
      (+)-catechin at saturating acceptor concentrations, which has not previously been
      reported for a beta-glucosidase and is difficult to achieve synthetically. 

PMID- 24682447
TI  - Does kyphotic deformity correlate with functional outcomes in fractures at the
      thoracolumbar junction treated by 360 degrees  instrumented fusion?
AB  - Sagittal balance and its relationship with back pain and functional outcomes has
      become an important factor in the management of thoracolumbar fractures. The
      kyphosis threshold at the thoracolumbar junction (TLJ) that produces a
      significant functional impairment remains unclear. Ninety-four patients who were
      treated surgically for TLJ fractures were evaluated after a follow-up period of 2
      10 years. Functional evaluation based on the Oswestry and Hannover Scores (HS)
      was performed. Additionally, such patients underwent clinical and radiological
      evaluation. A significant inversely proportional correlation between the HS and
      the degrees of local kyphosis ("K-Angle") (p = 0.0172) was found. A significant
      directly proportional correlation between Oswestry Score and "K-Angle" (p =
      0.0142) was found. Significantly poorer scores with both measurement tools
      (Hannover and Oswestry Scores) were found in patients with a kyphosis higher than
      12 degrees . 

PMID- 24682448
TI  - Ethnic density is not associated with psychological distress in Turkish-Dutch,
      Moroccan-Dutch and Surinamese-Dutch ethnic minorities in the Netherlands.
AB  - PURPOSE: Ethnic density, the proportion of people of the same ethnic group in the
      neighbourhood, has been identified as a protective factor with regard to mental
      health in ethnic minorities. Research on the putative intermediating factors,
      exposure to discrimination and improved social support, has not yielded
      conclusive evidence. We investigated the association between ethnic density and
      psychological well-being in three ethnic minority groups in the Netherlands. We
      also assessed whether a protective ethnic density effect is related to the degree
      to which each group experiences discrimination and social support at group level.
      METHODS: Using multi-level linear regression modelling, we studied the influence
      of ethnic density at neighbourhood level on psychological distress, measured with
      the Kessler Psychological Distress scale (K10), in 13,864 native Dutch, 1,206
      Surinamese-Dutch, 978 Turkish-Dutch and 784 Moroccan-Dutch citizens of the four
      major cities in the Netherlands. Based on a nationwide survey among ethnic
      minorities on social integration, ethnic groups were ordered with respect to the
      intermediating factors. RESULTS: Ethnic density was not associated with
      psychological distress in any of the three ethnic minority groups. As a
      consequence, we found no support for either experiences of discrimination or for
      own-group social interactions at group level as intermediating factors. In all
      three ethnic minority groups, as well as in the native Dutch group, individual
      demographic and socio-economic factors emerged as the main explanations for
      individuals' mental well-being. CONCLUSIONS: These results suggest that
      individual demographic and socio-economic risk characteristics outweigh the
      influence of neighbourhood attributes on mental health.

PMID- 24682449
TI  - Chronic ethanol exposure alters the lung proteome and leads to mitochondrial
      dysfunction in alveolar type 2 cells.
AB  - The lungs can undergo irreversible damage from chronic alcohol consumption.
      Herein, we developed an animal model predisposed for edematous lung injury
      following chronic ingestion of alcohol to better understand the etiology of
      alcohol-related disorders. Using animal modeling, alongside high-throughput
      proteomic and microarray assays, we identified changes in lung protein and
      transcript in mice and rats, respectively, following chronic alcohol ingestion or
      a caloric control diet. Liquid chromatography-mass spectrometry identified
      several mitochondrial-related proteins in which the expression was upregulated
      following long-term alcohol ingestion in mice. Consistent with these
      observations, rat gene chip microarray analysis of alveolar cells obtained from
      animals maintained on a Lieber-DeCarli liquid alcohol diet confirmed significant
      changes in mitochondrial-related transcripts in the alcohol lung. Transmission
      electron microscopy revealed significant changes in the mitochondrial
      architecture in alcohol mice, particularly following lipopolysaccharide exposure.
      Chronic alcohol ingestion was also shown to worsen mitochondrial respiration,
      mitochondrial membrane polarization, and NAD(+)-to-NADH ratios in alveolar type 2
      cells. In summary, our studies show causal connection between chronic alcohol
      ingestion and mitochondrial dysfunction, albeit the specific role of each of the
      mitochondrial-related proteins and transcripts identified in our study requires
      additional study. 

PMID- 24682450
TI  - Alveolar type II cells maintain bioenergetic homeostasis in hypoxia through
      metabolic and molecular adaptation.
AB  - Although many lung diseases are associated with hypoxia, alveolar type II
      epithelial (ATII) cell impairment, and pulmonary surfactant dysfunction, the
      effects of O(2) limitation on metabolic pathways necessary to maintain cellular
      energy in ATII cells have not been studied extensively. This report presents
      results of targeted assays aimed at identifying specific metabolic processes that
      contribute to energy homeostasis using primary ATII cells and a model ATII cell
      line, mouse lung epithelial 15 (MLE-15), cultured in normoxic and hypoxic
      conditions. MLEs cultured in normoxia demonstrated a robust O(2) consumption rate
      (OCR) coupled to ATP generation and limited extracellular lactate production,
      indicating reliance on oxidative phosphorylation for ATP production.
      Pharmacological uncoupling of respiration increased OCR in normoxic cultures to
      175% of basal levels, indicating significant spare respiratory capacity. However,
      when exposed to hypoxia for 20 h, basal O(2) consumption fell to 60% of normoxic
      rates, and cells maintained only ~50% of normoxic spare respiratory capacity,
      indicating suppression of mitochondrial function, although intracellular ATP
      levels remained at near normoxic levels. Moreover, while hypoxic exposure
      stimulated glycogen synthesis and storage in MLE-15, glycolytic rate (as measured
      by lactate generation) was not significantly increased in the cells, despite
      enhanced expression of several enzymes related to glycolysis. These results were
      largely recapitulated in murine primary ATII, demonstrating MLE-15 suitability
      for modeling ATII metabolism. The ability of ATII cells to maintain ATP levels in
      hypoxia without enhancing glycolysis suggests that these cells are exceptionally
      efficient at conserving ATP to maintain bioenergetic homeostasis under O(2)
      limitation.

PMID- 24682452
TI  - Joseph Black, carbon dioxide, latent heat, and the beginnings of the discovery of
      the respiratory gases.
AB  - The discovery of carbon dioxide by Joseph Black (1728-1799) marked a new era of
      research on the respiratory gases. His initial interest was in alkalis such as
      limewater that were thought to be useful in the treatment of renal stone. When he
      studied magnesium carbonate, he found that when this was heated or exposed to
      acid, a gas was evolved that he called "fixed air" because it had been combined
      with a solid material. He showed that the new gas extinguished a flame, that it
      could not support life, and that it was present in gas exhaled from the lung.
      Within a few years of his discovery, hydrogen, nitrogen, and oxygen were also
      isolated. Thus arguably Black's work started the avalanche of research on the
      respiratory gases carried out by Priestley, Scheele, Lavoisier, and Cavendish.
      Black then turned his attention to heat and he was the first person to describe
      latent heat, that is the heat added or lost when a liquid changes its state, for
      example when water changes to ice or steam. Latent heat is a key concept in
      thermal physiology because of the heat lost when sweat evaporates. Black was a
      friend of the young James Watt (1736-1819) who was responsible for the
      development of early steam engines. Watt was puzzled why so much cooling was
      necessary to condense steam into water, and Black realized that the answer was
      the latent heat. The resulting improvements in steam engines ushered in the
      Industrial Revolution.

PMID- 24682451
TI  - Conditioned media from mesenchymal stromal cells restore sodium transport and
      preserve epithelial permeability in an in vitro model of acute alveolar injury.
AB  - Mesenchymal stromal cells (MSCs) or their media (MSC-M) were reported to reverse
      acute lung injury (ALI)-induced decrease of alveolar fluid clearance. To
      determine the mechanisms by which MSC-M exert their beneficial effects, an in
      vitro model of alveolar epithelial injury was created by exposing primary rat
      alveolar epithelial cells (AECs) to hypoxia (3% O2) plus cytomix, a combination
      of IL-1beta, TNF-alpha, and IFN-gamma. MSC-M were collected from human MSCs
      exposed for 12 h to either normoxia (MSC-M) or to hypoxia plus cytomix (HCYT-MSC
      M). This latter condition was used to model the effect of alveolar inflammation
      and hypoxia on paracrine secretion of MSCs in the injured lung. Comparison of
      paracrine soluble factors in MSC media showed that the IL-1 receptor antagonist
      and prostaglandin E2 were markedly increased while keratinocyte growth factor
      (KGF) was twofold lower in HCYT-MSC-M compared with MSC-M. In AECs, hypoxia plus
      cytomix increased protein permeability, reduced amiloride-sensitive short-circuit
      current (AS-Isc), and also decreased the number of alpha-epithelial sodium
      channel (alpha-ENaC) subunits in the apical membrane. To test the effects of MSC
      media, MSC-M and HCYT-MSC-M were added for an additional 12 h to AECs exposed to
      hypoxia plus cytomix. MSC-M and HCYT-MSC-M completely restored epithelial
      permeability to normal. MSC-M, but not HCYT-MSC-M, significantly prevented the
      hypoxia plus cytomix-induced decrease of ENaC activity and restored apical alpha
      ENaC channels. Interestingly, KGF-deprived MSC-M were unable to restore amiloride
      sensitive sodium transport, indicating a possible role for KGF in the beneficial
      effect of MSC-M. These results indicate that MSC-M may be a preferable
      therapeutic option for ALI. 

PMID- 24682453
TI  - [Treatment of proximal humeral fractures in Germany: Influence of the level of
      hospital care and the frequency of treatment].
AB  - BACKGROUND: Various treatment options exist for displaced proximal humeral
      fractures. The impact of the level of hospital care and frequency of treatment on
      current treatment regimens in Germany was analyzed. MATERIAL AND METHODS: A total
      of 576 hospitals were included. The survey covered questions on frequency,
      diagnostics, classification, therapy, complications, and clinical scenarios.
      RESULTS: In all, 48% of the hospitals returned the questionnaire: 73% treat more
      than 60% of the fractures surgically, mainly with angle-stable implants. The
      angle-stable plate is the treatment of choice for young patients, but older
      patients are treated using other treatment options. Problems and complications
      included malreduction, secondary displacement, screw perforation, avascular
      necrosis, and impingement. According to treatment indication, implant choice, and
      common complications, no significant differences between the level of hospital
      care and frequency of treatment were observed. CONCLUSION: Independent of the
      level of hospital care and frequency of treatment, there is a trend for head
      preserving angular-stable surgery with a homogenous level of treatment in
      Germany.

PMID- 24682458
TI  - Tougher action is needed to address "alarming" levels of overweight and obesity,
      says England's chief medical officer.

PMID- 24682459
TI  - Application of T-DNA activation tagging to identify glutamate receptor-like genes
      that enhance drought tolerance in plants.
AB  - KEY MESSAGE: A high-quality rice activation tagging population has been developed
      and screened for drought-tolerant lines using various water stress assays. One
      drought-tolerant line activated two rice glutamate receptor-like genes.
      Transgenic overexpression of the rice glutamate receptor-like genes conferred
      drought tolerance to rice and Arabidopsis. Rice (Oryza sativa) is a multi-billion
      dollar crop grown in more than one hundred countries, as well as a useful
      functional genetic tool for trait discovery. We have developed a population of
      more than 200,000 activation-tagged rice lines for use in forward genetic screens
      to identify genes that improve drought tolerance and other traits that improve
      yield and agronomic productivity. The population has an expected coverage of more
      than 90 % of rice genes. About 80 % of the lines have a single T-DNA insertion
      locus and this molecular feature simplifies gene identification. One of the lines
      identified in our screens, AH01486, exhibits improved drought tolerance. The
      AH01486 T-DNA locus is located in a region with two glutamate receptor-like
      genes. Constitutive overexpression of either glutamate receptor-like gene
      significantly enhances the drought tolerance of rice and Arabidopsis, thus
      revealing a novel function of this important gene family in plant biology.

PMID- 24682460
TI  - Length of the dark period affects flower opening and the expression of circadian
      clock associated genes as well as xyloglucan endotransglucosylase/hydrolase genes
      in petals of morning glory (Ipomoea nil).
AB  - KEY MESSAGE: We isolated differentially expressed and dark-responsive genes
      during flower development and opening in petals of morning glory. Flower opening
      usually depends on petal expansion and is regulated by both genetic and
      environmental factors. Flower opening in morning glory (Ipomoea nil) is
      controlled by the dark/light regime just prior to opening. Opening was normal
      after 8- or 12-h dark periods but progressed very slowly after a 4-h dark period
      or in continuous light. Four genes (InXTH1-InXTH4) encoding xyloglucan
      endotransglucosylase/hydrolases (XTHs) and three genes (InEXPA1-InEXPA3) encoding
      alpha-expansins (EXPAs) were isolated. The expression patterns of InXTH2, InXTH3,
      and InXTH4 in petals were closely correlated with the rate of flower opening
      controlled by the length of the dark period prior to opening, but those of the
      EXPA genes were not. The expression pattern of InXTH1 gene was closely correlated
      with petal elongation. Suppression subtractive hybridization was used to isolate
      dark-responsive genes accompanying flower opening. The expressions of ten
      isolated genes were associated with the length of the dark period prior to flower
      opening. One gene was highly homologous to Arabidopsis pseudo-response
      regulator7, which is associated with the circadian clock and phytochrome
      signaling; another to Arabidopsis REVEILLE1, which affects the output of the
      circadian clock. Other genes were related to light responses, plant hormone
      effects and signal transduction. The possible roles of these genes in regulation
      of flower opening are discussed.

PMID- 24682461
TI  - A novel NAC transcription factor from Suaeda liaotungensis K. enhanced transgenic
      Arabidopsis drought, salt, and cold stress tolerance.
AB  - KEY MESSAGE: Sl NAC1 functions as a stress-responsive NAC protein involved in the
      abscisic acid-dependent signaling pathway and enhances transgenic Arabidopsis
      drought, salt, and cold stress tolerance. NAC (NAM, ATAF1, 2, CUC2) transcription
      factors constitute the largest families of plant-specific transcription factors,
      known to be involved in various growth or developmental processes and in
      regulation of response to environmental stresses. However, only little
      information regarding stress-related NAC genes is available in Suaeda
      liaotungensis K. In this study, we cloned a full-length NAC gene (1,011 bp) named
      SlNAC1 using polymerase chain reaction from Suaeda liaotungensis K. and
      investigated its function by overexpression in transgenic Arabidopsis. SlNAC1
      contains an NAC-conserved domain. Its expression in S. liaotungensis was induced
      by drought, high-salt, and cold (4  degrees C) stresses and by abscisic acid.
      Subcellular localization experiments in onion epidermal cells indicated that
      SlNAC1 is localized in the nucleus. Yeast one-hybrid assays showed that SlNAC1
      functions as a transcriptional activator. SlNAC1 transgenic Arabidopsis displayed
      a higher survival ratio and lower rate of water loss under drought stress; a
      higher germination ratio, higher survival ratio, and lower root inhibition rate
      under salt stress; a higher survival ratio under cold stress; and a lower
      germination ratio and root inhibition rate under abscisic acid treatment,
      compared with wild-type Arabidopsis. These results suggested that SlNAC1
      functions as a stress-responsive NAC protein involved in the abscisic acid
      dependent signaling pathway and may have potential applications in transgenic
      breeding to enhance crops' abiotic stress tolerances.

PMID- 24682462
TI  - Cervical cancer screening: the complex interplay of medical infrastructure,
      society, and culture.

PMID- 24682463
TI  - Eribulin monotherapy in patients aged 70 years and older with metastatic breast
      cancer.
AB  - PURPOSE: Following the demonstrated efficacy and safety of eribulin mesylate in
      heavily pretreated patients with metastatic breast cancer, an exploratory
      analysis was performed to investigate the effect of age in these patients.
      METHODS: Data were pooled from two single-arm phase II studies and one open-label
      randomized phase III study in which patients received eribulin mesylate at 1.4
      mg/m(2) as 2- to 5-minute intravenous infusions on days 1 and 8 of a 21-day
      cycle. The effect of age on median overall survival (OS), progression-free
      survival (PFS), overall response rate (ORR), clinical benefit rate (CBR), and
      incidence of adverse events (AEs) was calculated for four age groups (<50 years,
      50-59 years, 60-69 years, >= 70 years). RESULTS. Overall, 827 patients were
      included in the analysis (<50 years, n = 253; 50-59 years, n = 289; 60-69 years,
      n = 206; >= 70 years, n = 79). Age had no significant impact on OS (11.8 months,
      12.3 months, 11.7 months, and 12.5 months, respectively; p = .82), PFS (3.5
      months, 2.9 months, 3.8 months, and 4.0 months, respectively; p = .42), ORR
      (12.7%, 12.5%, 6.3%, and 10.1%, respectively), or CBR (20.2%, 20.8%, 20.4%, and
      21.5%, respectively). Although some AEs had higher incidence in either the
      youngest or the oldest subgroup, there was no overall effect of age on the
      incidence of AEs (including neuropathy, neutropenia, and leukopenia). CONCLUSION:
      Eribulin monotherapy in these selected older patients with good baseline
      performance status led to OS, PFS, ORR, CBR, and tolerability similar to those of
      younger patients with metastatic breast cancer. The benefits and risks of
      eribulin appear to be similar across age groups.

PMID- 24682464
TI  - Mitomycin C and high-dose 5-fluorouracil with folinic acid as a therapeutic
      option for heavily pretreated patients with metastatic colorectal cancer:
      prospective phase II trial.
AB  - BACKGROUND: Standard treatment for patients with unresectable colorectal cancer
      metastases includes chemotherapy regimens based on irinotecan, oxaliplatin,
      fluoropyrimidines, anti-vascular endothelial growth factor therapy, and anti
      EGFR. Additional therapeutic options are needed for patients with good
      performance status who have disease progression during or after standard
      therapies. METHODS: A nonrandomized phase II study was modeled as a two-stage
      Chen design. Eligible patients had a diagnosis of metastatic colorectal cancer
      (mCRC) with progression after prior cytotoxic regimens based on oxaliplatin and
      irinotecan. Treatment consisted of mitomycin C in combination with high-dose 5
      fluorouracil (5-FU) and folinic acid (the MLF regimen; mitomycin C as an
      intravenous bolus of 6 mg/m2 i.v. on days 1 and 22 every 7 weeks; folinic acid at
      250 mg/m2 in combination with 5-FU at 2,600 mg/m2 as a continuous intravenous
      infusion (24 hours) weekly for 6 of every 7 weeks. RESULTS: The median age of the
      74 eligible patients was 62 years (range: 47-79 years). In these heavily
      pretreated patients with mCRC, the MLF regimen was the fourth or fifth line in
      more than 60% of the patients. Two patients (3.2%) achieved a partial response,
      and 33 (53.2%) achieved a best response of stable disease, defined as neither
      sufficient shrinkage to qualify for partial response nor sufficient increase to
      qualify for progressive disease. Median progression-free survival was 4.9 months.
      The median overall survival was 9.7 months. The most common nonhematologic side
      effects included mucositis (24.4% for all grades, and 9.5% with grade 3/4),
      diarrhea (15.0% for all grades, 13.6% with grade 3/4), fatigue (44.7% for all
      grades, 13.6% with grade 3/4), nausea (12.3% for all grades, 6.8% with grade
      3/4), and peripheral neuropathy (17.6% for all grades, 2.7% with grade 3/4).
      Among the most frequent hematological toxicities were neutropenia (27.1% for all
      grades, 14.9% with grade 3/4), thrombocytopenia (18.9% for all grades, 8.1% with
      grade 3/4), and anemia (13.6% for all grades, 4.1% with grade 3/4). Dose
      reductions due to adverse events were necessary in 29 of 74 patients (37.6%), and
      discontinuation of therapy due to toxicity was necessary for 14 of 74 patients
      (18.2%). CONCLUSION: Our study shows the MLF regimen can be administered safely
      to patients with heavily pretreated mCRC. Median progression-free and overall
      survival compares favorably with other options used or approved in this setting.
      A randomized trial in this setting should be considered.

PMID- 24682465
TI  - Randomized phase II trial comparing carboplatin plus weekly paclitaxel and
      docetaxel alone in elderly patients with advanced non-small cell lung cancer:
      north japan lung cancer group trial 0801.
AB  - BACKGROUND: Standard first-line chemotherapy for elderly non-small cell lung
      cancer (NSCLC) patients has been monotherapy with vinorelbine or gemcitabine.
      Docetaxel has also been considered as an alternative option for the elderly
      population in Japan. We have previously demonstrated the high efficacy of
      carboplatin plus weekly paclitaxel for elderly NSCLC patients. Consequently, we
      conducted a randomized phase II study to select the proper regimen for a future
      phase III trial. METHODS: Eligible patients were aged 70 years or older with
      newly diagnosed advanced NSCLC. Patients were randomly assigned either to a
      combination of carboplatin (area under the curve: 6 mg/mL per minute) with weekly
      paclitaxel (70 mg/m2) (CP regimen) or to single-agent docetaxel (60 mg/m2). The
      primary endpoint of this study was objective response rate. Secondary endpoints
      were progression-free survival, overall survival, and toxicity profile. RESULTS:
      Among 83 eligible patients (41 to CP, 42 to docetaxel), the objective response
      rates were 54% (95% confidence interval: 39%-69%) and 24% (95% confidence
      interval: 11%-37%) and median progression-free survival was 6.6 months and 3.5
      months in the CP arm and the docetaxel arm, respectively. Severe neutropenia,
      febrile neutropenia, and nausea were significantly frequent in the docetaxel arm,
      whereas toxicities in the CP arm were generally moderate. One treatment-related
      death was observed in the docetaxel arm. CONCLUSION: The CP regimen achieved
      higher activity with less toxicity than single-agent docetaxel. Considering the
      results of this phase II trial and the IFCT-0501 trial, we have selected the CP
      regimen for a future phase III trial in elderly patients with advanced NSCLC.

PMID- 24682466
TI  - 19-substituted benzoquinone ansamycin heat shock protein-90 inhibitors:
      biological activity and decreased off-target toxicity.
AB  - The benzoquinone ansamycins (BQAs) are a valuable class of antitumor agents that
      serve as inhibitors of heat shock protein (Hsp)-90. However, clinical use of BQAs
      has resulted in off-target toxicities, including concerns of hepatotoxicity.
      Mechanisms underlying the toxicity of quinones include their ability to redox
      cycle and/or arylate cellular nucleophiles. We have therefore designed 19
      substituted BQAs to prevent glutathione conjugation and nonspecific interactions
      with protein thiols to minimize off-target effects and reduce hepatotoxicity. 19
      Phenyl- and 19-methyl-substituted versions of geldanamycin and its derivatives,
      17-allylamino-17-demethoxygeldanamycin and 17-(dimethylaminoethylamino)-17
      demethoxygeldanamycin (17-DMAG), did not react with glutathione, whereas marked
      reactivity was observed using parent BQAs. Importantly, although 17-DMAG induced
      cell death in primary and cultured mouse hepatocytes, 19-phenyl and 19-methyl
      DMAG showed reduced toxicity, validating the overall approach. Furthermore, our
      data suggest that arylation reactions, rather than redox cycling, are a major
      mechanism contributing to BQA hepatotoxicity. 19-Phenyl BQAs inhibited purified
      Hsp90 in a NAD(P)H: quinone oxidoreductase 1 (NQO1)-dependent manner,
      demonstrating increased efficacy of the hydroquinone ansamycin relative to its
      parent quinone. Molecular modeling supported increased stability of the
      hydroquinone form of 19-phenyl-DMAG in the active site of human Hsp90. In human
      breast cancer cells, 19-phenyl BQAs induced growth inhibition also dependent upon
      metabolism via NQO1 with decreased expression of client proteins and compensatory
      induction of Hsp70. These data demonstrate that 19-substituted BQAs are
      unreactive with thiols, display reduced hepatotoxicity, and retain Hsp90 and
      growth-inhibitory activity in human breast cancer cells, although with diminished
      potency relative to parent BQAs.

PMID- 24682467
TI  - Epirubicin upregulates UDP glucuronosyltransferase 2B7 expression in liver cancer
      cells via the p53 pathway.
AB  - Anthracyclines are effective genotoxic anticancer drugs for treating human
      malignancies; however, their clinical use is limited by tumor resistance and
      severe cardiotoxicity (e.g., congestive heart failure). Epirubicin (EPI) is less
      cardiotoxic compared with other canonical anthracyclines (e.g., doxorubicin).
      This has been attributed to its unique glucuronidation detoxification pathway.
      EPI is primarily inactivated by UDP-glucuronosyltransferase 2B7 (UGT2B7) in the
      liver. Hence, the regulation of hepatic UGT2B7 expression is critical for EPI
      systemic clearance but remains poorly characterized. We show herein that EPI
      upregulates UGT2B7 expression in hepatocellular carcinoma (HCC) HepG2 and Huh7
      cells. Our analyses of deleted and mutated UGT2B7 promoter constructs identified
      a p53 response element (p53RE) in the UGT2B7 promoter. EPI stimulated UGT2B7
      promoter activity via this p53RE and enhanced in vivo p53 binding at this p53RE
      in HepG2 cells. Knockdown of p53 expression by small interfering RNA silencing
      technology significantly repressed the capacity of EPI to stimulate UGT2B7
      transcription. Furthermore, the p53 activator nutlin-3alpha significantly
      enhanced UGT2B7 expression and recruited the p53 protein to the UGT2B7 p53RE in
      HepG2 cells. Collectively, our results demonstrated that EPI promotes its own
      detoxification via the p53-mediated pathway. This regulation may contribute to
      tumor resistance to EPI-containing HCC chemotherapy and may also provide a new
      explanation for the reduced cardiotoxicity of EPI compared with other
      anthracyclines. Our finding also suggests that upon exposure to genotoxic agents,
      detoxifying genes are activated by the p53-mediated pathway to clear genotoxic
      agents locally within the tumor site or even systemically through the liver. 

PMID- 24682468
TI  - Professor Martin Barratt 1936-2014.

PMID- 24682471
TI  - Choice for response alternatives differing in reinforcement frequency in dopamine
      D2 receptor mutant and Swiss-Webster mice.
AB  - RATIONALE: A previous study showed that dopamine (DA) D2 receptors (D2Rs) are
      involved in the reinforcing effectiveness of food, but the specific involvement
      of DA D2Rs in choice among food reinforcers remains unclear. OBJECTIVES: The
      current study used genetic and pharmacological approaches to assess the role of
      D2Rs in choice among food-reinforcement frequencies using the generalized
      matching law (GML), which specifies that logged response and time allocation
      ratios vary linearly with logged reinforcer ratios. METHODS: Congenic D2R
      knockout (KO) and wild-type (WT) mice were exposed to concurrent variable
      interval schedules of reinforcement with scheduled relative-reinforcement rates
      from 4:1 to 1:4. Effects of the D2R antagonist (-)-eticlopride (0.1-1.0 mg/kg)
      were assessed in Swiss-Webster mice. RESULTS: Response and time allocation ratios
      were related to obtained reinforcement ratios as predicted by the GML. GML fits
      accounted for >= 92 % of the variance in allocation ratios and did not differ in
      D2R KO and WT mice. Similarly, there were no significant effects of (-)
      eticlopride dose on GML fits, despite effects on overall response rates.
      CONCLUSIONS: The current results demonstrate that neither deletion nor acute
      blockade of D2Rs affects choice among response alternatives varying in food
      reinforcement frequencies. Because previously published results suggest a role of
      D2Rs in choice between response alternatives differing in reinforcer magnitude
      and delay or magnitude and probability, the current findings suggest that D2Rs
      play a role in choice only among certain parameters of reinforcement.
      Furthermore, these findings suggest parameters of reinforcement may only be
      fungible in a complex manner.

PMID- 24682469
TI  - Tracking migration during human T cell development.
AB  - Specialized microenvironments within the thymus are comprised of unique cell
      types with distinct roles in directing the development of a diverse, functional,
      and self-tolerant T cell repertoire. As they differentiate, thymocytes transit
      through a number of developmental intermediates that are associated with unique
      localization and migration patterns. For example, during one particular
      developmental transition, immature thymocytes more than double in speed as they
      become mature T cells that are among the fastest cells in the body. This
      transition is associated with dramatic changes in the expression of chemokine
      receptors and their antagonists, cell adhesion molecules, and cytoskeletal
      components to direct the maturing thymocyte population from the cortex to
      medulla. Here we discuss the dynamic changes in behavior that occur throughout
      thymocyte development, and provide an overview of the cell-intrinsic and
      extrinsic mechanisms that regulate human thymocyte migration. 

PMID- 24682472
TI  - The relationship between post traumatic stress disorder and post traumatic
      growth: gender differences in PTG and PTSD subgroups.
AB  - PURPOSE: This study investigated the post traumatic stress disorder (PTSD) and
      post traumatic growth (PTG) in 2,300 earthquake survivors 1 year after the 2008
      Wenchuan earthquake. This study aimed to investigate the relationship between
      PTSD and PTG and also tested for the gender differences in PTSD and PTG
      subgroups. METHODS: A stratification random sampling strategy and questionnaires
      were used to collect the data. The PTSD was assessed using the PTSD Check list
      Civilian and the PTG was assessed using the Post traumatic growth inventory.
      2,300 individuals were involved in the initial survey with 2,080 completing the
      final questionnaire, a response rate of 90.4%. One-way ANOVA analyses were
      performed to investigate the gender differences in the PTSD and PTG subgroups.
      RESULTS: One year following the earthquake, 40.1 and 51.1% of survivors reported
      PTSD and PTG, respectively. A bivariate correlation analysis indicated that there
      was a positive association between PTG and PTSD. The PTG and PTSD variance
      analysis conducted on female and male subgroups suggested that women were more
      affected than men. CONCLUSIONS: Given the relatively high PTG prevalence, it was
      concluded that researchers need to pay more attention to the positive outcomes of
      an earthquake rather than just focusing on the negative effects. The surveys and
      analyses indicated that psychological intervention and care for the earthquake
      disaster survivors should focus more on females and older people, who tend to be
      more adversely affected.

PMID- 24682473
TI  - Education, income and alcohol misuse: a stress process model.
AB  - PURPOSE: This study applies stress process theory to study and explain the
      negative association between socioeconomic status (SES) and alcohol misuse. SES
      is theorized to reduce alcohol misuse by reducing exposure to stressors and
      increasing access to resources. METHODS: The National Co-Morbidity panel sample
      (N = 4,979) interviewed in 1990-1992 and 2000-2002 are analyzed to estimate
      direct and indirect pathways between SES and alcohol misuse over time via
      stressors and resources. RESULTS: Higher education and income predict decreased
      alcohol misuse via internal and external locus of control. External locus of
      control is associated with increased alcohol intake over time, whereas internal
      locus of control is associated with a lower likelihood of developing future
      alcohol-related disorders. Income is also associated with increased alcohol
      misuse via religiosity, which is more common among people of low income, and
      protects against alcohol misuse. CONCLUSIONS: SES is negatively associated with
      alcohol misuse because low SES increases people's perceptions that their lives
      are determined by luck, and reduces their sense of personal control. However, low
      income has a countervailing negative influence on alcohol misuse via its
      association with religiosity.

PMID- 24682474
TI  - Production and functional characterization of a novel fungal immunomodulatory
      protein FIP-SN15 shuffled from two genes of Ganoderma species.
AB  - Fungal immunomodulatory protein (FIP), extracted from higher basidiomycetes, is a
      kind of small molecule protein with extensive biological functions, including
      anti-tumor and anti-allergy, stimulating immune cells to produce a variety of
      cytokines, etc. Compared with FIP-glu, FIP-SN15, a novel gene shuffled from the
      genes of Ganoderma sinensis and Ganoderma lucidum FIP, was used as the object in
      this study. Based on the construction of prokaryotic expression vectors, both
      pET30a-FIP-glu and pET30a-FIP-SN15 were expressed in Escherichia coli. Then the
      recombinant proteins are respectively analyzed by Western blot, Q-TOF MS, and
      bioinformatics techniques. Finally, effects of reFIPs on cell cycle and apoptosis
      of human glioblastoma cell line U-251 MG were studied by fluorescence activated
      cell sorting (FACS). The results showed that the recombinant proteins FIP-SN15
      and FIP-glu could be successfully expressed in E. coli, the yield of which was
      35.95 and 36.67 mg/L, respectively. The recombinant protein FIP-SN15 consisted of
      111 amino acids, and four peptides were identified by Q-TOF MS with a coverage of
      91.9 %. The secondary and tertiary structure of FIP-SN15 were also predicted by
      bioinformatics method which suggest that reFIP-SN15 was a new member of FIPs
      family. FACS analysis showed that 10 MUg/mL FIP-SN15 and FIP-glu could induce U
      251 MG cells apoptosis, the apoptotic rates were increased by 6.03 and 22.01 %,
      respectively. The results of reFIPs on U-251 MG cell cycle indicated that reFIPs
      could inhibit cell cycle progression by retardation of G1/S transition. The
      efforts in this assay would lay the foundation for further development of reFIPs
      products and research on the anti-tumor mechanisms of FIP-SN15. 

PMID- 24682475
TI  - Construction of an engineered strain capable of degrading two isomeric
      nitrophenols via a sacB- and gfp-based markerless integration system.
AB  - In this study, a gfp-based novel markerless allelic exchange integration system
      was developed. By employing gfp gene and sacB gene as counter-selectable markers,
      an ortho-nitrophenol degradation operon (onpABC gene cluster) was successfully
      inserted into the chromosome of meta-nitrophenol utilizer Cupriavidus necator
      JMP134. Through two rounds of recombination, the engineered strain (strain JMP134
      ONP) was directly selected from the plate by fluorescence screening and has the
      ability to degrade both ortho-nitrophenol and meta-nitrophenol, simultaneously.
      This relatively simple and efficient method can be used as an alternative
      strategy of allelic exchange insertion for the application of metabolic
      engineering in various bacterial strains, complementary to existing gene knock-in
      procedures.

PMID- 24682476
TI  - Towards molecular, physiological, and biochemical understanding of photosynthetic
      inhibition and oxidative stress in the toxic Alexandrium tamarense induced by a
      marine bacterium.
AB  - Alexandrium tamarense is a notorious harmful algal bloom species, which is
      associated with the largest number of paralytic shellfish poisoning cases,
      causing devastating economic losses and health hazards. The marine bacterium
      Mangrovimonas yunxiaonensis strain LY01 showed high algicidal effects on A.
      tamarense. A. tamarense was also susceptible to the supernatant of LY01 as
      revealed by algicidal activity assay, but washed bacterial cells did not show
      algicidal activity towards A. tamarense. In this study, we investigated the
      algicidal effect of the supernatant on growth, photosynthesis and the
      antioxidative response of A. tamarense. The results indicated that under the
      algicidal effect of the supernatant, the contents of cellular pigments including
      chlorophyll a and carotenoids were significantly decreased, and the decline of
      the maximum quantum yield and relative electron transport rate values suggested
      that photosynthetic inhibition occurred in the photosystem II system. The content
      of reactive oxygen species (ROS) increased after 0.5 h exposure, and the surplus
      ROS induced lipid peroxidation, the destruction of cellular membrane integrity
      and decreased cellular protein and carbohydrate contents in the algal cells. At
      the same time, the supernatant also induced the responses of antioxidant enzymes
      and non-enzymatic antioxidant. The transcription of photosynthesis- and
      respiration-related genes were significantly inhibited during the exposure
      procedure, which obstructed photosynthetic efficiency and capacity and disturbed
      the respiratory system, thereby increasing ROS production again. All these
      results elaborate clearly the entire procedure by which cellular physiological
      levels respond to the algicidal bacterium and may contribute to a better
      understanding of the bacterial control of A. tamarense.

PMID- 24682477
TI  - The specificity of alpha-glucosidase from Saccharomyces cerevisiae differs
      depending on the type of reaction: hydrolysis versus transglucosylation.
AB  - Our investigation of the catalytic properties of Saccharomyces cerevisiae alpha
      glucosidase (AGL) using hydroxybenzyl alcohol (HBA) isomers as transglucosylation
      substrates and their glucosides in hydrolytic reactions demonstrated interesting
      findings pertaining to the aglycon specificity of this important enzyme. AGL
      specificity increased from the para(p)- to the ortho(o)-HBA isomer in
      transglucosylation, whereas such AGL aglycon specificity was not seen in
      hydrolysis, thus indicating that the second step of the reaction (i.e., binding
      of the glucosyl acceptor) is rate-determining. To study the influence of
      substitution pattern on AGL kinetics, we compared AGL specificity, inferred from
      kinetic constants, for HBA isomers and other aglycon substrates. The demonstrated
      inhibitory effects of HBA isomers and their corresponding glucosides on AGL
      catalyzed hydrolysis of p-nitrophenyl alpha-glucoside (PNPG) suggest that HBA
      glucosides act as competitive, whereas HBA isomers are noncompetitive,
      inhibitors. As such, we postulate that aromatic moieties cannot bind to an active
      site unless an enzyme-glucosyl complex has already formed, but they can interact
      with other regions of the enzyme molecule resulting in inhibition. 

PMID- 24682478
TI  - Aspergillus niger RhaR, a regulator involved in L-rhamnose release and
      catabolism.
AB  - The genome of the filamentous fungus Aspergillus niger is rich in genes encoding
      pectinases, a broad class of enzymes that have been extensively studied due to
      their use in industrial applications. The sequencing of the A. niger genome
      provided more knowledge concerning the individual pectinolytic genes, but little
      is known about the regulatory genes involved in pectin degradation. Understanding
      regulation of the pectinolytic genes provides a tool to optimize the production
      of pectinases in this industrially important fungus. This study describes the
      identification and characterization of one of the activators of pectinase
      encoding genes, RhaR. Inactivation of the gene encoding this regulator resulted
      in down-regulation of genes involved in the release of L-rhamnose from the pectin
      substructure rhamnogalacturonan I, as well as catabolism of this monosaccharide.
      The rhaR disruptant was unable to grow on L-rhamnose, but only a small reduction
      in growth on pectin was observed. This is likely caused by the presence of a
      second, so far unknown regulator that responds to the presence of D-galacturonic
      acid. 

PMID- 24682479
TI  - Effects of codon optimization on the mRNA levels of heterologous genes in
      filamentous fungi.
AB  - Filamentous fungi, particularly Aspergillus species, have recently attracted
      attention as host organisms for recombinant protein production. Because the
      secretory yields of heterologous proteins are generally low compared with those
      of homologous proteins or proteins from closely related fungal species, several
      strategies to produce substantial amounts of recombinant proteins have been
      conducted. Codon optimization is a powerful tool for improving the production
      levels of heterologous proteins. Although codon optimization is generally
      believed to improve the translation efficiency of heterologous genes without
      affecting their mRNA levels, several studies have indicated that codon
      optimization causes an increase in the steady-state mRNA levels of heterologous
      genes in filamentous fungi. However, the mechanism that determines the low mRNA
      levels when native heterologous genes are expressed was poorly understood. We
      recently showed that the transcripts of heterologous genes are polyadenylated
      prematurely within the coding region and that the heterologous gene transcripts
      can be stabilized significantly by codon optimization, which is probably
      attributable to the prevention of premature polyadenylation in Aspergillus
      oryzae. In this review, we describe the detailed mechanism of premature
      polyadenylation and the rapid degradation of mRNA transcripts derived from
      heterologous genes in filamentous fungi. 

PMID- 24682480
TI  - Heterologous expression of pyrroloquinoline quinone (pqq) gene cluster confers
      mineral phosphate solubilization ability to Herbaspirillum seropedicae Z67.
AB  - Gluconic acid secretion mediated by the direct oxidation of glucose by
      pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (GDH) is
      responsible for mineral phosphate solubilization in Gram-negative bacteria.
      Herbaspirillum seropedicae Z67 (ATCC 35892) genome encodes GDH apoprotein but
      lacks genes for the biosynthesis of its cofactor PQQ. In this study, pqqE of
      Erwinia herbicola (in plasmid pJNK1) and pqq gene clusters of Pseudomonas
      fluorescens B16 (pOK53) and Acinetobacter calcoaceticus (pSS2) were over
      expressed in H. seropedicae Z67. Transformants Hs (pSS2) and Hs (pOK53) secreted
      micromolar levels of PQQ and attained high GDH activity leading to secretion of
      33.46 mM gluconic acid when grown on 50 mM glucose while Hs (pJNK1) was
      ineffective. Hs (pJNK1) failed to solubilize rock phosphate, while Hs (pSS2) and
      Hs (pOK53) liberated 125.47 MUM and 168.07 MUM P, respectively, in minimal medium
      containing 50 mM glucose under aerobic conditions. Moreover, under N-free minimal
      medium, Hs (pSS2) and Hs (pOK53) not only released significant P but also showed
      enhanced growth, biofilm formation, and exopolysaccharide (EPS) secretion.
      However, indole acetic acid (IAA) production was suppressed. Thus, the addition
      of the pqq gene cluster, but not pqqE alone, is sufficient for engineering
      phosphate solubilization in H. seropedicae Z67 without compromising growth under
      nitrogen-fixing conditions. 

PMID- 24682481
TI  - Managing the cultivation and processing of microalgae to prolong storage in water
      in-oil emulsions.
AB  - Producing biofuel from microalgae on a large scale will require high biomass
      productivity using systems such as high-rate raceway ponds. The vast scale of
      proposed raceway ponds, spanning 247 to 988 acres per farm, suggests practices
      currently used in commercial monoculture agricultural systems will need to be
      adopted for cultivation of algae. In commercial crop production, monoculture is
      facilitated by a well-established seed production, distribution, and delivery
      system. Currently, no such system exists for microalgae. The aims of this study
      were to investigate the application of water-in-oil (W/O) emulsions for the
      storage of microalgae and the management steps required to prolong cell
      viability. Water-in-oil emulsions were prepared with Chlorella sorokiniana, C.
      minutissima, C. vulgaris var. vulgaris, and C. vulgaris to investigate the
      impacts of cell cultivation medium and cell acclimation prior to emulsification
      on cell viability during storage. For emulsions prepared with C. sorokiniana,
      cells that received an acclimation treatment 24 h between cell separation from
      the cultivation medium and emulsification survived over 100 days longer than
      cells that did not receive an acclimation treatment. Emulsions prepared with C.
      sorokiniana grown in medium containing 29.7 mM KNO3, 1.66 mM MgSO4 . 7H2O, and
      0.85 mM FeSO4 . 2H2O had higher levels of viable cells after 100 days of storage
      compared to cells grown in medium containing 9.90 mM KNO3 and 0.20 mM MgSO4 .
      7H2O with no FeSO4 . 2H2O. The results indicate that processing of cells can be
      managed to increase the stability of microalgae in W/O emulsions.

PMID- 24682482
TI  - A plant malonyl-CoA synthetase enhances lipid content and polyketide yield in
      yeast cells.
AB  - Malonyl-CoA is the essential building block of natural products such as fatty
      acids, polyketides, and flavonoids. Engineering the biosynthesis of fatty acids
      is important for biofuel production while that of polyketides provides precursors
      of medicines and nutritional supplements. However, microorganisms maintain a
      small amount of cellular malonyl-CoA, which could limit production of lipid and
      polyketides under certain conditions. Malonyl-CoA concentration is regulated by
      multiple pathways and signals, and changes in intracellular malonyl-CoA often
      lead to complex alterations in metabolism. In the present work, overexpression of
      a plant malonyl-CoA synthetase gene (AAE13) in Saccharomyces cerevisiae resulted
      in 1.6- and 2.4-fold increases in lipid and resveratrol accumulation
      simultaneously. We also demonstrated that AAE13 partially complemented the
      temperature-sensitive acc1 mutant, replacing this key enzyme in central
      metabolism. Mechanistic analysis by CoA quantification and transcriptomic
      measurement suggested that increases in malonyl-CoA concentration were coupled
      with drastic reductions in other major CoA compounds and clear suppression of
      tricarboxylic acid cycle-related genes. These results suggest that malonyl-CoA is
      a critical target for fatty acid and polyketide engineering and that
      overexpression of malonyl-CoA synthetic enzymes needs to be combined with
      upregulation of CoA synthesis to maintain metastasis of central metabolism.

PMID- 24682483
TI  - Characteristics and biotechnology applications of aliphatic amino acid
      hydroxylases belonging to the Fe(II)/alpha-ketoglutarate-dependent dioxygenase
      superfamily.
AB  - The asymmetric hydroxylation of inactive carbon atoms is still an important
      reaction in the industrial synthesis of valuable chiral compounds such as
      pharmaceuticals and fine chemicals. Applications of monooxygenation enzymes, like
      cytochrome P450 monooxygenases, flavin-containing monooxygenases, and
      Fe(II)/alpha-ketoglutarate-dependent dioxygenases (Fe/alphaKG-DOs), are strongly
      desired as hydroxylation biocatalysts because they have great advantages in regio
      and stereoselectivity of the reactions. Recently, several novel Fe/alphaKG-DOs
      have been found to catalyze the asymmetric hydroxylation of aliphatic amino
      acids. Depending on their amino acid sequences, these Fe/alphaKG-DOs catalyze
      different types of regioselective hydroxylations, or C3-, C4-, and C5
      hydroxylation. Additionally, most also have stereoselective sulfoxidation
      activities. Here, we have reviewed the characterization and process development
      of this novel functioning group of Fe/alphaKG-DOs. 

PMID- 24682484
TI  - Effects of mutations at threonine-654 on the insoluble glucan synthesized by
      Leuconostoc mesenteroides NRRL B-1118 glucansucrase.
AB  - Twelve different amino acids were each substituted for threonine-654 in a cloned
      glucansucrase from Leuconostoc mesenteroides NRRL B-1118. Both the native and the
      cloned enzyme with threonine at position 654 produced a water-insoluble glucan
      containing approximately 44 mol% 1,3-disubstituted alpha-D-glucopyranosyl units
      and 29 mol% 1,6-disubstituted alpha-D-glucopyranosyl units. Several substitutions
      yielded an enzyme that produced an increased percentage of 1,3-disubstituted
      alpha-D-glucopyranosyl units, with corresponding decreases in 1,6-disubstituted
      alpha-D-glucopyranosyl units. Only one substitution, tyrosine, resulted in a
      significant increase in the percentage of 1,6-disubstituted alpha-D
      glucopyranosyl units, with a concomitant increase in glucan yield. The mutated
      enzymes that produced the highest levels of 1,3-disubstituted alpha-D
      glucopyranosyl units were also significantly activated by the addition of
      dextran, but glucan yields were also lower in these mutants.

PMID- 24682485
TI  - Antibody ligation of CM1 on cisplatin-exposed HeLa cells induces apoptosis
      through reactive oxygen species-dependent Fas ligand expression.
AB  - Centrocyte/centroblast marker 1 (CM1) has been identified as a pro-apoptosis
      molecule on B-cell lymphoma cells as well as several types of cancer cells. In
      this study, we investigated its signaling mechanism in HeLa cells after treatment
      with cisplatin in order to potentially identify a new therapeutic target. The CM1
      molecule was induced on the surface of cisplatin-exposed HeLa cells. In these
      cells, ligation of CM1 with anti-CM1 monoclonal antibodies inhibited cell
      proliferation and produced reactive oxygen species. Fas ligand (FasL) expression
      was upregulated without upregulating Fas in cisplatin-exposed HeLa cells after
      CM1 stimulation. Pretreatment with N-acetylcysteine, a pan-capase inhibitor, and
      ZB4, an antagonistic anti-Fas antibody, effectively inhibited the apoptotic
      effect triggered by CM1. CM1 ligation induced apoptosis through disruption of the
      mitochondrial membrane potential, decreased Bcl-2 and phosphorylated ERK
      expression. These findings identify CM1 as a potential new therapeutic target
      related to cisplatin-exposed cervical cancer. 

PMID- 24682486
TI  - Mercury exposure and health impacts among individuals in the artisanal and small
      scale gold mining community: a comprehensive review.
AB  - BACKGROUND: Mercury (Hg) is used in gold mining to extract gold from ore by
      forming "amalgam"-a mixture composed of approximately equal parts mercury and
      gold. Approximately 15 million people, including approximately 3 million women
      and children, participate in artisanal small-scale gold mining (ASGM) in
      developing countries. Thirty-seven percent of global air emissions of Hg are
      produced by ASGM. The recently adopted Minamata Convention calls for nations to
      gather health data, train health-care workers, and raise awareness in regard to
      ASGM activity. OBJECTIVE: The purpose of our review was to evaluate the current
      literature regarding the health effects of Hg among those working and/or living
      in or near ASGM communities. METHODS: We searched PubMed, ScienceDirect, and
      Google Scholar for studies relating to health effects and biomarkers of Hg
      exposure in ASGM communities. Articles published from 1990 through December 2012
      were evaluated for relevance. DISCUSSION: Studies reporting health assessments,
      kidney dysfunction, neurological disorders and symptoms, and
      immunotoxicity/autoimmune dysfunction in individuals living in or near an ASGM
      community were identified. More than 60 studies that measured biomarkers of Hg
      exposure in individuals living in or near ASGM communities were also identified.
      These studies, conducted in 19 different countries in South America, Asia, and
      Africa, demonstrated that hair and urine concentrations are well above World
      Health Organization health guidance values in ASGM communities. CONCLUSIONS: ASGM
      workers and their families are exposed to Hg vapor, and workers, workers'
      families, and residents of nearby and downstream communities are consuming fish
      heavily contaminated with methylmercury.

PMID- 24682487
TI  - [A guide to successful public relations for hospitals and emergency medical
      services].
AB  - Tragic accidents, e.g. involving celebrity patients or severe incidents in
      hospital occur suddenly without any advance warning, often produce substantial
      interest by the media and quickly overburden management personnel involved in
      both hospitals and emergency medical services. While doctors, hospitals and
      emergency medical services desire objective media reports, the media promote
      emotionalized and dramatized reports to ensure maximum attention and circulation.
      When briefing the media, the scales may quickly tilt from professional, well
      deliberated information to unfortunate, often unintended disinformation. Such
      phenomena may result in continuing exaggerated reports in the tabloid press,
      which in the presence of aggressive lawyers and a competitive hospital
      environment can turn into image and legal problems. In this article, several
      aspects are discussed in order to achieve successful public relations.Interviews
      should be given only after consultation with the responsible press officer and
      the director of the respective department or hospital director. Requests for
      information by the media should always be answered as otherwise one-sided,
      unintentional publications can result that are extremely difficult to correct
      later. One should be available to be contacted easily by journalists, regular
      press conferences should be held and critics should be taken seriously and not be
      brushed off. Questions by journalists should be answered in a timely manner as
      journalists are continuously under time pressure and do not understand
      unnecessary delays. Information for the media should always be provided at the
      same time, no publication should be given preference and an absolutely current
      list of E-mail contacts is required. When facing big events a press conference is
      preferred as many questions can be answered at once. Always be well prepared for
      an interview or even for just a statement. Each interview should be regarded as
      an opportunity to put a story forward which you wanted to do for a long time and
      your message should not contain more than three main points.Each hospital or
      emergency medical service should have a professional department for public
      relations, an exact knowledge of the regional and national media and strategies
      how to handle an incident that is of interest for the media. The media should be
      provided with information not only when a negative incident has happened but
      should be provided with regular positive messages as well. An interview must be
      carefully prepared to achieve a good image. 

PMID- 24682488
TI  - Support for US health reform law rises slightly, poll finds.

PMID- 24682490
TI  - Arthroscopic treatment of osteochondral lesion of olecranon.

PMID- 24682489
TI  - Post-operative limb position can influence blood loss and range of motion after
      total knee arthroplasty: a systematic review.
AB  - PURPOSE: A consistent post-operative limb positioning regime could be an
      attractive, simple and cost-effective alternative to improve patient's outcomes
      after total knee arthroplasty (TKA). The aim of this study was to perform a
      systematic review of the available literature in order to understand whether a
      consistent post-operative limb positioning regime could affect blood loss and
      range of motion (ROM) after TKA. METHODS: A search was performed using the
      keywords "total knee replacement/knee prosthesis" in combination with "post
      operative management", "blood loss", "range of motion", "leg position",
      "flexion", "extension" and "splinting" regardless of the year of publication. The
      scientific databases have been accessed in order to identify papers dealing with
      post-operative limb positioning regimes after TKA. RESULTS: Seven articles
      matching the inclusion criteria were selected. Blood loss and ROM were both
      investigated in all but one paper, in which only blood loss was evaluated. There
      were six randomized controlled trials and one prospective comparative study. A 48
      72 h post-operative knee flexion protocol seems to be effective in reducing blood
      loss and increasing ROM following TKA. We did also find no benefit in using
      extension splints in the immediate post-operative period. CONCLUSIONS: Based on
      the studies undertaken to date, a 48-72 h post-operative knee flexion protocol
      should be implemented as an easy and inexpensive method of reducing blood loss
      and increasing ROM following TKA. Shorter flexion regimes failed to influence
      these parameters.

PMID- 24682491
TI  - Femoral marrow cavity bone harvesting used for arthroscopic refilling of
      misplaced or enlarged bone tunnels in revision ACL surgery: an arthroscopically
      supported technique with antegrade intramedullary bone harvesting by a reamer
      irrigator-aspirator (RIA) system.
AB  - PURPOSE: In anterior cruciate ligament (ACL) revision surgery, refilling of
      misplaced or enlarged tunnels frequently requires bone harvesting from the iliac
      crest. Unfortunately, donor-site pain displays a relevant complication. In order
      to optimize patients' comfort, we developed a procedure combining minimally
      invasive intramedullary bone harvesting from the femur with arthroscopic tunnel
      refilling. METHODS: Patients with ACL reconstruction failure that were not
      eligible for one-step revision surgery but required tunnel refilling prior to the
      next ACL reconstruction were enrolled prospectively. Cancellous bone was
      harvested intramedullarily from the ipsilateral femur using the reamer-irrigator
      aspirator system in a minimally invasive manner. Afterwards, the femoral and
      tibial tunnels were arthroscopically refilled using cones and push rods. Computer
      tomography (CT) analyses were carried out before and after the filling procedure.
      Pain levels were assessed during the entire follow-up. Patients undergoing iliac
      crest bone harvesting for other reasons served as a control group. Finally, the
      quality of the newly formed bone stock was evaluated in the subsequent ACL
      reconstruction procedure. RESULTS: Five patients were included during a 6-month
      period. Prior to refilling, tunnel analysis revealed a mean tunnel volume of 7.9
      cm(3) at the femur [SD +/- 5.3 cm(3)] and of 6.7 cm(3) [SD +/- 5.1 cm(3)] at the
      tibia. The CT analyses further revealed that graft failure was predominantly
      caused by tunnel misplacement. Post-operatively, pain levels due to
      intramedullary bone harvesting were significantly lower compared to iliac crest
      bone harvesting at every analysed time point. Three to five months after tunnel
      filling, CT analyses showed sufficiently incorporated bone stocks with filling
      rates of 75 % femoral and 94 % tibial. ACL revision surgery was performed 4-5
      months after tunnel filling without any complication. CONCLUSION: Intramedullary
      bone harvesting from the ipsilateral femur combined with arthroscopic refilling
      of the bone tunnels ensures a high-quality bone stock for further ACL
      reconstruction. The clinical relevance is shown by the feasibility of this
      technique and the significantly reduced pain levels during post-operative
      recovery.

PMID- 24682492
TI  - Metformin does not attenuate the acute insulin-sensitizing effect of a single
      bout of exercise in individuals with insulin resistance.
AB  - Combining metformin and exercise is recommended for the treatment of insulin
      resistance. However, it has been suggested that metformin blunts the insulin
      sensitizing effects of exercise. We evaluated in a group of insulin-resistant
      patients the interactions between exercise and their daily dose of metformin. Ten
      insulin-resistant patients underwent insulin sensitivity assessment using
      intravenous glucose tolerance test after an overnight fast in the following
      conditions: (1) after taking their habitual morning dose of metformin (MET), (2)
      after 45 min of high intensity interval exercise having withheld metformin during
      24 h (EX), and (3) after their habitual metformin dose plus an identical exercise
      bout (MET + EX). During the exercise trials (EX and MET + EX), energy expenditure
      and substrate oxidation were assessed by indirect calorimetry. In addition, 12-h
      postprandial blood glucose was measured in all three trials. Insulin sensitivity
      was similar between MET and EX [4.0 +/- 0.8 and 4.1 +/- 0.7 * 10(-4) min(-1) (MUU
      mL)(-1); P = 0.953] but was 43 % higher than both MET and EX after MET + EX (NS;
      P = 0.081). Blood glucose disappearance rate was higher after MET + EX than after
      MET or EX trials (1.7 +/- 0.2, 1.0 +/- 0.1, and 1.2 +/- 0.1 % min(-1),
      respectively; P = 0.020). There was no difference in postprandial blood glucose
      concentration after the three meals that followed the trials (P = 0.446).
      Exercise energy expenditure was 9 % higher during MET + EX than during EX (P =
      0.015) partly due to increased carbohydrate oxidation. Our data suggest that
      habitual metformin treatment in insulin-resistant patients does not blunt the
      acute insulin-sensitizing effects of a single bout of exercise that on the
      contrary, tends to enhance it. 

PMID- 24682493
TI  - The T-line as an intraoperative landmark for reproducing the native femoral
      anteversion during hip arthroplasty.
AB  - INTRODUCTION: Three-dimensional computed tomographic (CT)-based preoperative
      planning for total hip arthroplasty (THA) enabled us to evaluate the cut surface
      of the femoral neck osteotomy. When we planned the stem placement in 20 degrees 
      of anteversion, we noticed that the line connecting the trochanteric fossa and
      the middle of the medial cortex of the femoral neck (T line) was coincident with
      the component torsion in many cases. We attempted to evaluate the accuracy of the
      T line for reproducing the native femoral anteversion during THA comparing it
      with the midcortical line, the reference guide previously reported by Suh.
      MATERIALS AND METHODS: The institutional review board allowed a retrospective
      review of CT images of 100 normal hip joints. We performed virtual THA using the
      non-anatomic straight stem at three different cutting heights of 5, 10, or 15 mm
      above the lesser trochanter. The anteversion of the stem implanted parallel to
      the T line or midcortical line was measured. RESULTS: The mean difference of the
      stem anteversion using the T line and the native femoral anteversion was -0.77o
      (95 % CI: -1.92o to 0.38o), 0.69o (95 % CI: -0.42o to 1.79o) and 3.38o (95 % CI:
      2.29o-4.46o) at cutting heights of 5, 10 and 15 mm, respectively. Using the
      midcortical line, stems tended to retroversion. CONCLUSIONS: Aligning the stem
      parallel to the T line on the cut surface provides a good reproduction of the
      femoral anteversion. The T line can be an useful intraoperative reference guide
      for the anteversion of the femoral component in THA for patients without severe
      hip deformity.

PMID- 24682494
TI  - Complications of hip fracture surgery on patients receiving clopidogrel therapy.
AB  - INTRODUCTION: Clopidogrel (Plavix((r))) may influence patient safety during
      fracture surgery. Our study examines the incidence of complications for patients
      undergoing hemiarthroplasty on clopidogrel therapy. MATERIALS AND METHODS: All
      patients, who underwent hemiarthroplasty between 2005 and 2011 were
      retrospectively reviewed. Patients were placed in two comparative groups based on
      the use of clopidogrel antiplatelet therapy. Records were reviewed for patient
      demographics, ASA score, pre and postoperative hemoglobin, time to surgery,
      length of stay, bleeding events, transfusions and complications. Comparative
      statistical analysis was performed using Fisher's exact test and Student's t
      test, using P < 0.05 to identify statistical significance. RESULTS: A total of
      203 charts were reviewed, of which 162 patients met inclusion/exclusion criteria.
      One hundred and twelve females and 50 males with mean age of 84 years were
      identified. The clopidogrel group consisted of 15 (9.3 %) patients and the
      nonclopidogrel group 147 (90.7 %). The clopidogrel group had more comorbidities
      resulting in a significantly higher ASA score (3.9 vs. 2.9), and lower
      preoperative hemoglobin (11.3 vs. 12.0). There was no significant difference
      identified in time to surgery, intraoperative blood loss, hemoglobin on days 1-3,
      or number of transfusions received between groups. Patients on clopidogrel were
      seen to have significantly longer hospital stays (10.6 vs. 7.4 days). However, a
      similar rate of wound and bleeding related complications (6.7 vs. 6.1 %) was
      seen. CONCLUSIONS: The optimal treatment for hip fracture patients on
      antiplatelet therapy is unclear. However, in this study there appears to be no
      significant difference with regards to bleeding and bleeding related wound
      complications, suggesting it is safe to proceed with hemiarthroplasty for
      patients receiving clopidogrel.

PMID- 24682498
TI  - Ursolic acid suppresses growth and adrenocorticotrophic hormone secretion in
      AtT20 cells as a potential agent targeting adrenocorticotrophic hormone-producing
      pituitary adenoma.
AB  - Adrenocorticotrophic hormone (ACTH)-producing pituitary adenoma leads to excess
      ACTH secretion, which is associated with significant mortality and impaired
      quality of life. Thus far, the first line therapy is the transphenoidal
      microsurgery. Considering the high recurrence rate and complications of surgery,
      novel agents, which directly target on pituitary ACTH-producing adenoma and
      suppress ACTH secretion are urgently required. In the present study, the effect
      of ursolic acid (UA) as a candidate agent targeting ACTH-producing AtT20 cells
      was investigated. It was demonstrated that UA inhibited the viability and induced
      apoptosis of AtT20 cells and decreased ACTH secretion. The process of apoptosis
      involved a decrease of the B cell lymphoma 2 (Bcl-2)/Bcl2-associated X protein
      ratio followed by a release of mitochondrial cytochrome c into the cytosol with
      subsequent activation of caspase-9, -3/7 and -8. The potential signaling pathway
      involved the activation of c-Jun N-terminal kinase (JNK) but not extracellular
      signal-regulated protein kinases1/2 and p38 mitogen-activated protein kinase. The
      JNK pathway participated in UA-induced mitochondrial apoptotic signaling
      transduction via increasing the phosphorylation and degradation of Bcl-2, which
      may be partly attenuated by the JNK inhibitor SP600125. In conclusion, the
      present study indicates that UA may be a promising candidate agent for the
      management of ACTH-producing pituitary adenoma.

PMID- 24682495
TI  - Clinical research data warehouse governance for distributed research networks in
      the USA: a systematic review of the literature.
AB  - OBJECTIVE: To review the published, peer-reviewed literature on clinical research
      data warehouse governance in distributed research networks (DRNs). MATERIALS AND
      METHODS: Medline, PubMed, EMBASE, CINAHL, and INSPEC were searched for relevant
      documents published through July 31, 2013 using a systematic approach. Only
      documents relating to DRNs in the USA were included. Documents were analyzed
      using a classification framework consisting of 10 facets to identify themes.
      RESULTS: 6641 documents were retrieved. After screening for duplicates and
      relevance, 38 were included in the final review. A peer-reviewed literature on
      data warehouse governance is emerging, but is still sparse. Peer-reviewed
      publications on UK research network governance were more prevalent, although not
      reviewed for this analysis. All 10 classification facets were used, with some
      documents falling into two or more classifications. No document addressed costs
      associated with governance. DISCUSSION: Even though DRNs are emerging as vehicles
      for research and public health surveillance, understanding of DRN data governance
      policies and procedures is limited. This is expected to change as more DRN
      projects disseminate their governance approaches as publicly available toolkits
      and peer-reviewed publications. CONCLUSIONS: While peer-reviewed, US-based DRN
      data warehouse governance publications have increased, DRN developers and
      administrators are encouraged to publish information about these programs.

PMID- 24682499
TI  - The effects of lobeline on nicotine withdrawal-induced depression-like behavior
      in mice.
AB  - RATIONALE: Evidence suggests that neuronal nicotinic acetylcholine receptor
      (nAChR) ligand lobeline has antidepressant-like properties. OBJECTIVES: The
      present study investigated the effects of lobeline on nicotine withdrawal-induced
      depression-like behavior. METHODS: Adult C57BL/6J mice were exposed to nicotine
      (200 MUg/ml) in drinking solution for 3 weeks. During withdrawal, depression-like
      behavior was measured by the forced swim test (FST). We also determined
      norepinephrine (NE) levels in the prefrontal cortex (PFC) and hippocampus during
      nicotine withdrawal. Furthermore, we determined the effects of repeated treatment
      with lobeline or a selective alpha4beta2 nAChR ligand 3-(pyridine-3-yl)-cytisine
      on brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-responsive
      element binding (p-CREB) protein expression in the hippocampus. RESULTS:
      Withdrawal from chronic nicotine increased immobility time in the FST, a measure
      for depression-like behavior. Pretreatment with lobeline significantly decreased
      immobility time during nicotine withdrawal. In addition, pretreatment with
      lobeline attenuated nicotine withdrawal-induced increased NE levels in the PFC
      and hippocampus. Further, repeated treatment with lobeline or 3-(pyridine-3-yl)
      cytisine decreased immobility time in the FST and reduced withdrawal-induced
      increased BDNF and p-CREB expression in the hippocampus. CONCLUSIONS: Taken
      together, our results indicate that lobeline attenuated nicotine withdrawal
      induced depression-like behavior likely by targeting brain nAChRs, noradrenergic
      neurotransmission, and/or hippocampal BDNF. Thus, lobeline may have some
      potential to prevent smoking relapse by counteracting nicotine withdrawal-induced
      depression in humans.

PMID- 24682500
TI  - Aberrant glutamate signaling in the prefrontal cortex and striatum of the
      spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.
AB  - RATIONALE: Attention-deficit/hyperactivity disorder (ADHD) is thought to involve
      hypofunctional catecholamine systems in the striatum, nucleus accumbens, and
      prefrontal cortex (PFC); however, recent clinical evidence has implicated
      glutamate dysfunction in the pathophysiology of ADHD. Recent studies show that
      increased stimulation of dopamine D2 and D4 receptors causes inhibition of N
      methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptors, respectively. The spontaneously hypertensive rat (SHR) model of ADHD
      combined type (C) has been found to have a hypofunctional dopamine system in the
      ventral striatum, nucleus accumbens, and PFC compared to the control Wistar Kyoto
      (WKY) strain. OBJECTIVES: Based on the current understanding of typical dopamine
      glutamate interactions, we hypothesized that the SHR model of ADHD would have a
      hyperfunctional glutamate system terminating in the striatum, nucleus accumbens,
      and PFC. RESULTS: High-speed amperometric recordings combined with four-channel
      microelectrode arrays to directly measure glutamate dynamics showed increased
      evoked glutamate release in the PFC (cingulate and infralimbic cortices, p <
      0.05) and also in the striatum (p < 0.05) of the SHR (ADHD-C) as compared to the
      WKY. Finally, glutamate uptake was discovered to be aberrant in the PFC, but not
      the striatum, of the SHR when compared to the control WKY strain. CONCLUSIONS:
      These results suggest that the glutamatergic system in the PFC of the SHR model
      of ADHD is hyperfunctional and that targeting glutamate in the PFC could lead to
      the development of novel therapeutics for the treatment of ADHD.

PMID- 24682501
TI  - Pharmacological profile of a 17beta-heteroaryl-substituted neuroactive steroid.
AB  - RATIONALE: In order to improve upon the pharmacological properties of the
      neuroactive steroid ganaxolone, it was used as the starting point in the design
      of novel neurosteroids that replace the 17beta-acetyl side chain with an
      isoxazole bioisostere. OBJECTIVES: UCI-50027 (3-[3alpha-hydroxy-3beta-methyl
      5alpha-androstan-17beta-yl]-5-(hydroxymethyl)isoxazole) was designed as an orally
      active neuroactive steroid specifically targeted at the gamma-aminobutyric
      acid(A) receptor (GABAAR). METHODS: UCI-50027 was tested in vitro in Xenopus
      oocytes expressing human GABAARs and in vivo as an anticonvulsant, for ataxic
      effects and for anxiolytic activity. RESULTS: In vitro, UCI-50027 dose
      dependently enhanced the activity of GABA at human alpha1beta2gamma2L,
      alpha2beta1gamma2L, and alpha4beta3delta GABAARs. Consistent with its action as a
      positive allosteric modulator (PAM), it had no direct activity in the absence of
      GABA. UCI-50027 protected against acute pentylenetetrazol (PTZ)-induced
      convulsions with an ED50 of 6 mg/kg p.o. In the rotarod (RR) paradigm in mice,
      the AD50 (the ataxic dose where half of the animals fail the RR test) was found
      to be 38 mg/kg p.o., giving a therapeutic index (TI = RR AD50/PTZ ED50)~6 versus
      2.8 for ganaxolone. In the mouse-elevated plus maze (EPM) model for anxiety, UCI
      50027 showed a minimum effective dose (MED) <=0.3 mg/kg p.o. Thus, the TI (TI =
      RR AD50/EPM MED) for the compound as an anxiolytic is >=127 versus 3.3 for
      ganaxolone. CONCLUSIONS: UCI-50027 is an orally active neuroactive steroid with
      pharmacological activity consistent with a GABAAR PAM that has an improved
      separation between anticonvulsant/anxiolytic and rotarod effects, potent activity
      as an anticonvulsant and anxiolytic when compared to ganaxolone.

PMID- 24682502
TI  - Modafinil augments brain activation associated with reward anticipation in the
      nucleus accumbens.
AB  - RATIONALE: The nucleus accumbens (NAc) works as a key brain structure of the
      reward system, in which reward-related neural activity is well correlated with
      dopamine release from mesolimbic dopaminergic neurons. OBJECTIVES: Since
      modafinil can modulate dopaminergic transmission through re-uptake inhibition of
      dopamine, we investigated whether modafinil affects the reward-related brain
      activity in the NAc in healthy subjects. METHODS: Twenty healthy participants
      underwent two series of functional magnetic resonance imaging while performing
      monetary incentive delay task in which they were cued to anticipate and respond
      to a rapidly presented target to gain or avoid losing varying amounts of money,
      under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD)
      activation signals during gain and loss anticipations were analyzed in the NAc as
      an a priori region of interest as well as the whole brain. RESULTS: Modafinil
      significantly changed subjective feelings toward positive ones. The activation of
      BOLD signals was observed during gain anticipation under the placebo and
      modafinil conditions in the left and bilateral NAc, respectively. The modafinil
      condition showed significantly higher BOLD signal change at the highest gain
      (+Y500) cue compared to the placebo condition. CONCLUSIONS: The present study
      showed that modafinil affects reward processing in the NAc in healthy subjects
      through enhancing more positive anticipation, and it may provide a basis for the
      use of this drug for treating anhedonia observed in psychiatric disorders.

PMID- 24682504
TI  - The effects of caffeine on option generation and subsequent choice.
AB  - RATIONALE: Although the effects of caffeine on basic cognitive functions are well
      known, its effects on more complex decision making, particularly on option
      generation, is yet to be explored. OBJECTIVE: We examined the effects of caffeine
      on option generation in decision making using everyday life decisional
      situations. METHODS: In a double-blind placebo-controlled experiment,
      participants (N = 47) either received 300 mg of caffeine or a placebo.
      Participants had to generate choice options (things they could do) for a series
      of high and low familiar real-world scenarios and, subsequently, to decide among
      these options. RESULTS: Analyses revealed that participants in the caffeine
      condition generated significantly fewer options than participants in the placebo
      condition. Moreover, caffeine significantly reduced the option generation onset
      time, that is, participants in the caffeine condition generated their first
      option significantly faster than participants in the placebo condition. Regarding
      subsequent choice, we found evidence supporting the "take-the-first" heuristic,
      that is, the tendency to select the first generated option. This tendency was
      neither affected by caffeine nor by the familiarity of the scenarios.
      CONCLUSIONS: Caffeine results in fewer options generated in unconstrained real
      life decision-making situations and decreases generation onset times.

PMID- 24682503
TI  - Separate mechanisms for development and performance of compulsive checking in the
      quinpirole sensitization rat model of obsessive-compulsive disorder (OCD).
AB  - RATIONALE: Acute administration of serotonergic agonist, meta
      chlorophenylpiperazine (mCPP), attenuates performance of compulsive checking in
      an animal model of obsessive-compulsive disorder (OCD). It is not known whether
      mCPP has a similar effect on development of compulsive checking. OBJECTIVES: The
      objective of the study was to examine whether similar mechanisms mediate the
      development versus the performance of compulsive checking in the rat model.
      METHODS: Four groups of male rats (N = 14/group) were tested: two experimental
      groups co-injected with D2/D3 dopamine agonist quinpirole (0.25 mg/kg) and mCPP
      (0.625 mg/kg or 1.25 mg/kg), and two control groups, one co-injected with
      quinpirole and saline, the other receiving injections of saline. The time course
      of development of compulsive checking across injections 1 to 10 in quinpirole
      treated rats was compared to rats co-injected with quinpirole and mCPP. RESULTS:
      Results showed that during the course of chronic treatment, mCPP (1.25 mg/kg)
      significantly attenuated performance of checking behavior. However, when these
      rats were retested for expression of compulsive checking (that is, with an
      injection of quinpirole only), their profile of compulsive checking was no
      different from the control rats treated throughout with quinpirole only.
      CONCLUSIONS: Findings show that mCPP inhibits performance of compulsive checking
      but does not block quinpirole from inducing the neural substrate underlying this
      compulsive behavior. Hence, a separate mechanism underlies the induction of
      compulsive checking and the performance of it. It is suggested that development
      of the OCD endophenotype reflects neuroplastic changes produced by repeated
      dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors
      mediates a negative feedback signal that shuts down the motor performance of
      checking.

PMID- 24682506
TI  - How should I treat an accidentally misplaced 8 Fr drainage catheter in the right
      ventricle?

PMID- 24682505
TI  - Behavioural profile of exendin-4/naltrexone dose combinations in male rats during
      tests of palatable food consumption.
AB  - RATIONALE: The glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4
      potently suppresses food intake in animals and humans. However, little is known
      about the behavioural specificity of this effect either when administered alone
      or when co-administered with another anorectic agent. OBJECTIVES: The present
      study characterises the effects of exendin-4, both alone and in combination with
      naltrexone, on behaviours displayed by male rats during tests with palatable
      mash. METHODS: Experiment 1 examined the dose-response effects of exendin-4
      (0.025-2.5 MUg/kg, IP), while experiment 2 profiled the effects of low-dose
      combinations of the peptide (0.025 and 0.25 MUg/kg) and naltrexone (0.1 mg/kg).
      RESULTS: In experiment 1, exendin-4 dose dependently suppressed food intake as
      well as the frequency and rate of eating. However, these effects were accompanied
      by dose-dependent reductions in all active behaviours and, at 2.5 MUg/kg, a large
      increase in resting and disruption of the behavioural satiety sequence (BSS). In
      experiment 2, while exendin-4 (0.25 MUg/kg) and naltrexone each produced a
      significant reduction in intake and feeding behaviour (plus an acceleration in
      the BSS), co-treatment failed to produce stronger effects than those seen in
      response to either compound alone. CONCLUSION: Similarities between the
      behavioural signature of exendin-4 and that previously reported for the emetic
      agent lithium chloride would suggest that exendin-4 anorexia is related to the
      aversive effects of the peptide. Furthermore, as low-dose combinations of the
      peptide with naltrexone failed to produce an additive/synergistic anorectic
      effect, this particular co-treatment strategy would not appear to have
      therapeutic significance.

PMID- 24682507
TI  - A chromatin structure-based model accurately predicts DNA replication timing in
      human cells.
AB  - The metazoan genome is replicated in precise cell lineage-specific temporal
      order. However, the mechanism controlling this orchestrated process is poorly
      understood as no molecular mechanisms have been identified that actively regulate
      the firing sequence of genome replication. Here, we develop a mechanistic model
      of genome replication capable of predicting, with accuracy rivaling experimental
      repeats, observed empirical replication timing program in humans. In our model,
      replication is initiated in an uncoordinated (time-stochastic) manner at well
      defined sites. The model contains, in addition to the choice of the genomic
      landmark that localizes initiation, only a single adjustable parameter of direct
      biological relevance: the number of replication forks. We find that DNase
      hypersensitive sites are optimal and independent determinants of DNA replication
      initiation. We demonstrate that the DNA replication timing program in human cells
      is a robust emergent phenomenon that, by its very nature, does not require a
      regulatory mechanism determining a proper replication initiation firing sequence.

PMID- 24682508
TI  - Impact of variable CYP genotypes on breast cancer relapse in patients undergoing
      adjuvant tamoxifen therapy.
AB  - BACKGROUND: Tamoxifen is frequently used for the treatment of hormone receptor
      positive breast cancer (BC). Mainly CYP2D6 is responsible for the transformation
      to therapeutically active metabolites, but CYP2C19, CYP2C9 and CYP2B6 also are
      involved. We investigated the impact of polymorphisms within the genes encoding
      these CYP enzymes on the relapse-free time (RFT) in patients with BC. METHODS:
      Ninety-nine patients with hormone receptor positive BC, who had undergone
      adjuvant tamoxifen therapy, were genotyped for seventeen common variants within
      the genes encoding CYP2D6, CYP2C9, CYP2C19 and CYP2B6 using TaqMan and PCR-RFLP
      technology. Kaplan-Meier and Cox regression analyses were performed to elucidate
      the impact of genetic variants on RFT. Furthermore, CYP2D6 metabolic activity was
      determined in a subset of 50 patients by assessing dextromethorphan/dextrorphan
      urinary excretion ratios. CYP2D6 activity was compared to the CYP2D6 allelic
      combinations to evaluate the predictive value of the CYP2D6 genotyping results on
      phenotype. RESULTS: Although a trend toward longer RFTs in carriers of CYP2D6
      allele combinations encoding for extensive and ultrafast metabolizer phenotypes
      was observed, none of the investigated genetic variants had a statistically
      significant impact on RFT. The combined analysis of five major CYP2D6 variants
      was useful for the discrimination between poor and non-poor metabolizers.
      CONCLUSIONS: Comprehensive CYP2D6 genotyping has a good predictive value for
      CYP2D6 activity. Common variants in CYP2C9, CYP2C19, CYP2D6, and CYP2B6 did not
      have a significant impact on the RFT in this cohort of patients with BC.

PMID- 24682510
TI  - Desensitization protocol should not be used in acute lymphoblastic leukemia
      patients with silent inactivation of PEGasparaginase.

PMID- 24682509
TI  - Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab
      related secondary hypogammaglobulinemia: a single-center experience in 61
      patients.
AB  - Intravenous immunoglobulin replacement therapy represents the standard treatment
      for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders.
      Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated
      treatment approach in primary immunodeficiencies but no extensive data are
      available on their use in secondary hypogammaglobulinemia, a frequent phenomenon
      occurring after treatment with anti-CD20 monoclonal antibodies in
      lymphoproliferative disorders. In this retrospective study we evaluated efficacy
      (serum IgG trough levels, incidence of infections per year, need for antibiotics)
      and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus
      subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients.
      In addition, the impact of the infusion methods on quality of life was compared.
      All patients were treated with subcutaneous immunoglobulin, and 33 out of them
      had been previously treated with intravenous immunoglobulin. Both treatments
      appeared to be effective in replacing Ig production deficiency and in reducing
      the incidence of infectious events and the need for antibiotics. Subcutaneous
      immunoglobulin obtained a superior benefit when compared to intravenous
      immunoglobulin achieving higher IgG trough levels, lower incidence of overall
      infection and need for antibiotics. The incidence of serious bacterial infections
      was similar with both infusion ways. As expected, a lower number of adverse
      events was registered with subcutaneous immunoglobulin, compared to intravenous
      immunoglobulin, with no serious adverse events. Finally, we observed an
      improvement in health-related quality of life parameters after the switch to
      subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin
      is safe and effective in patients with hypogammaglobulinemia associated to
      lymphoproliferative disorders. 

PMID- 24682511
TI  - Frequent occurrence of non-malignant genetic alterations in clinical grade
      mesenchymal stromal cells expanded for cell therapy protocols.

PMID- 24682512
TI  - p53 protein expression independently predicts outcome in patients with lower-risk
      myelodysplastic syndromes with del(5q).
AB  - Del(5q) myelodysplastic syndromes defined by the International Prognostic Scoring
      System as low- or intermediate-1-risk (lower-risk) are considered to have an
      indolent course; however, recent data have identified a subgroup of these
      patients with more aggressive disease and poorer outcomes. Using deep sequencing
      technology, we previously demonstrated that 18% of patients with lower-risk
      del(5q) myelodysplastic syndromes carry TP53 mutated subclones rendering them at
      higher risk of progression. In this study, bone marrow biopsies from 85 patients
      treated with lenalidomide in the MDS-004 clinical trial were retrospectively
      assessed for p53 expression by immunohistochemistry in association with outcome.
      Strong p53 expression in >= 1% of bone marrow progenitor cells, observed in 35%
      (30 of 85) of patients, was significantly associated with higher acute myeloid
      leukemia risk (P=0.0006), shorter overall survival (P=0.0175), and a lower
      cytogenetic response rate (P=0.009), but not with achievement or duration of 26
      week transfusion independence response. In a multivariate analysis, p53-positive
      immunohistochemistry was the strongest independent predictor of transformation to
      acute myeloid leukemia (P=0.0035). Pyrosequencing analysis of laser
      microdissected cells with strong p53 expression confirmed the TP53 mutation,
      whereas cells with moderate expression predominantly had wild-type p53. This
      study validates p53 immunohistochemistry as a strong and clinically useful
      predictive tool in patients with lower-risk del(5q) myelodysplastic syndromes.
      This study was based on data from the MDS 004 trial (clinicaltrials.gov
      identifier: NCT00179621).

PMID- 24682513
TI  - Proinflammatory human 6-sulfo LacNAc-positive dendritic cells accumulate in
      intestinal acute graft-versus-host disease.

PMID- 24682514
TI  - Distribution and dietary regulation of an associated facultative Rhizobiales
      related bacterium in the omnivorous giant tropical ant, Paraponera clavata.
AB  - We document a facultative Bartonella-like Rhizobiales bacterium in the giant
      tropical ant, Paraponera clavata. In a lowland tropical rainforest in Costa Rica,
      59 colonies were assayed for the prevalence of the Bartonella-like bacterium
      (BLB), 14 of which were positive. We addressed three questions: First, how does
      the prevalence of BLB within colonies vary with environmental conditions? Second,
      how does diet affect the prevalence of BLB in P. clavata? Third, how does the
      distribution of BLB among colonies reflect ambient differences in food resources
      and foraging habits? A variety of environmental variables that may be predictive
      of the presence of BLB were measured, and diet manipulations were conducted to
      test whether the prevalence of BLB responded to supplemental carbohydrate or
      prey. The ambient frequency of BLB is much higher in young secondary forests, but
      is nearly absent from older secondary forests. The prevalence of BLB inside field
      colonies increased over the duration of a 2-week carbohydrate supplementation;
      however, water and prey supplementation did not alter the prevalence of BLB. The
      diets of the colonies located in young secondary forest, compared to other
      habitats, have a diet richer in carbohydrates and lower in prey. The abundance of
      carbohydrate, or the relative lack of N, in a colony's diet influences the
      occurrence of the BLB microbe in P. clavata. As experimental diet manipulations
      can affect the facultative presence of an N-cycling microbe, a consistent diet
      shift in diet may facilitate the emergence of tighter symbioses.

PMID- 24682515
TI  - NHS England's winter campaign: is earlier better?

PMID- 24682516
TI  - Surgeon's experience influences UKA survivorship: a comparative study between all
      poly and metal back designs.
AB  - PURPOSE: Concerns exist regarding prosthetic positioning and post-operative limb
      alignment in unicompartmental knee arthroplasty (UKA). In this study, we
      hypothesized deviations of the post-op anatomical femoro-tibial angle (aFTA) and
      the tibial component alignment to be factors influencing UKA survivorship.
      Moreover, by a comparison between all-poly and metal back UKAs, we hypothesized
      that prosthetic design plays a role in implant survivorship. METHODS: One hundred
      ninety-five medial UKAs were performed on 176 patients by two experienced
      surgeons and one low-UKA user. One hundred and forty-seven UKAs were included in
      the study: 72 all-poly and 75 metal back. Measurements were performed on
      radiographs: mechanical femoro-tibial angle, Cartier angle, aFTA and tibial
      posterior slope (PS) on pre-op radiographs; femoral and tibial component
      varus/valgus, aFTA and tibial component PS on post-op radiographs. RESULTS: At an
      average follow-up of 61 months (min. 30, max. 107), 147 UKAs were evaluated: The
      reported survivorship rate was 93.1 %. Eleven implants underwent revision: ten
      all-poly and one metal back. No differences were reported between the two groups
      in the radiographic measurements. Significant radiographic differences were
      reported between revised and not revised UKAs: Revised UKAs were associated with
      overcorrection of the pre-op Cartier angle and under correction of pre-op aFTA.
      Most of revised UKAs were performed by the low-volume UKA surgeon. CONCLUSIONS:
      Surgeon's experience is essential to achieve good results in UKA: Preserving the
      tibial epiphyseal axis and avoiding excessive or insufficient corrections of the
      pre-operative limb alignment are predictor of successful replacement, while
      prosthetic designs, models and fixation geometry do not affect UKA outcome. LEVEL
      OF EVIDENCE: IV.

PMID- 24682517
TI  - Short-term effects of partial meniscectomy on the clinical results of anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: This study aims to analyse the short-term effects of partial
      meniscectomy on the clinical results of anterior cruciate ligament reconstruction
      surgery. METHODS: Clinical outcomes of 19 patients who had partial medial
      meniscectomy and anterior cruciate ligament reconstruction during the same
      surgery (Group 1) were compared with the outcomes of 25 patients who had also
      reconstruction but did not have any meniscal lesion (Group 2). Median follow-up
      time was 29 months (range 12-67 months) in Group 1 and 27 months (range 12-70
      months) in Group 2. Feeling of apprehension in sports activities, International
      Knee Documentation Committee (IKDC) score, KT-2000 Arthrometer((r)) measurements
      and post-operative time to return to sports activity were the criteria for data
      analysis. RESULTS: Eight patients (42%) in Group 1 and 5 patients (20%) in Group
      2 stated feeling of apprehension in sports activities. IKDC score improved to A
      in 11 patients (58%) from Group 1, and 18 patients (72%) from Group 2. Mean
      anterior translation according to KT-2000 arthrometer measurements was 5.2 +/-
      1.3 mm in Group 1, and 4.6 +/- 1.3 mm in Group 2. Post-operative time to return
      to sports activity was 8.5 +/- 3.0 months in Group 1, and 6.5 +/- 2.2 months in
      Group 2. CONCLUSION: Partial meniscectomy for irreparable medial meniscal tears,
      applied during the same surgery with anterior cruciate ligament reconstruction,
      negatively affects the clinical outcomes in the short-term follow-up. This study
      may be a reference for long-term clinical trials and also future investigations
      of new methods in the treatment of similar cases. LEVEL OF EVIDENCE: IV.

PMID- 24682518
TI  - Year in review 2013: basic science and epidemiology.

PMID- 24682519
TI  - Pulmonary function, CT and echocardiographic abnormalities in sickle cell
      disease.
AB  - OBJECTIVES: To test the hypothesis that vascular abnormalities on high-resolution
      CT (HRCT) would be associated with echocardiographic changes and lung function
      abnormalities in patients with sickle cell disease (SCD) and the decline in lung
      function seen in SCD patients. METHODS: HRCT, echocardiography and lung function
      assessments were made in 35 adults, 20 of whom had previously been assessed a
      median of 6.6 years prior to this study. The pulmonary arterial dimensions on
      HRCT were quantified as the mean segmental pulmonary artery/bronchus (A/B) ratio
      and the summated cross-sectional area of all pulmonary vessels <5 mm in diameter
      (cross-sectional area (CSA)<5 mm%). RESULTS: The segmental A/B ratio was
      negatively correlated with FEV1, vital capacity (VC), forced expiratory flow
      between 25% and 75% of VC (FEF25/75) and arterial oxygen saturation (SpO2) and
      positively with the residual volume: total lung capacity ratio (RV:TLC) and
      respiratory system resistance (Rrs). CSA<5 mm% was negatively correlated with
      FEV1, FEF25/75 and SpO2 and positively with RV, RV:TLC and respiratory system
      resistance (Rrs). There were significant correlations between cardiac output
      assessed by echocardiography and the segmental A/B ratio and CSA<5 mm%. Lung
      function (FEV1 p=0.0004, VC p=0.0347, FEF25/75 p=0.0033) and the segmental A/B
      ratio (p=0.0347) and CSA<5 mm% (p<0.0001) significantly deteriorated over the
      follow-up period. CONCLUSIONS: Abnormalities in pulmonary vascular volumes may
      explain some of the lung function abnormalities and the decline in lung function
      seen in adults with SCD.

PMID- 24682520
TI  - Diagnostic performance of contrast-enhanced MR for acute appendicitis and
      alternative causes of abdominal pain in children.
AB  - OBJECTIVE: Unenhanced MRI has emerged as a useful tool for diagnosing pediatric
      acute appendicitis. The use of contrast-enhanced MRI for diagnosing pediatric
      appendicitis has not been documented. The purpose of this study is to examine the
      diagnostic performance of contrast-enhanced MRI for acute appendicitis and
      alternative entities in the pediatric population presenting with acute abdominal
      pain. MATERIALS AND METHODS: A retrospective review was conducted of 364
      consecutive pediatric patients undergoing contrast-enhanced MRI for the
      evaluation of possible appendicitis at a single institution between November 2012
      and September 2013. RESULTS: There were 132 cases of pathologically confirmed
      appendicitis out of 364 pediatric patients (36.3%) included in the study. Overall
      sensitivity and specificity were 96.2% (95% CI [91.4-98.4%]) and 95.7% (95% CI
      [92.3-97.6%]), respectively. Positive predictive value and negative predictive
      value were 92.7% (95% CI [86.6-96.3%]) and 97.8% (95% CI [94.7-99.1%]),
      respectively. The appendix was visualized in 243 cases (66.8%). Imaging confirmed
      alternative diagnoses in 75 patients, including most commonly colitis, enteritis
      or terminal ileitis (n = 25, 6.9%), adnexal cysts (n = 25, 6.9%) and mesenteric
      adenitis (n = 7, 1.9%). CONCLUSION: Contrast-enhanced MRI is capable of
      accurately diagnosing acute appendicitis while detecting many alternative
      entities of abdominal pain, and it allows good visualization of the appendix.
      Further evaluation is needed to determine whether contrast-enhanced MRI provides
      an advantage over non-enhanced MRI for imaging evaluation of acute abdominal pain
      in the pediatric population.

PMID- 24682523
TI  - The metaphyseal bone defect predicts outcome in reverse shoulder arthroplasty for
      proximal humerus fracture sequelae.
AB  - Reverse shoulder arthroplasty (RSA) represents an established procedure for
      treatment of fracture sequelae (FS) after proximal humerus fractures. The present
      work evaluates which factors are of influence for the clinical outcome. Fifty
      cases (mean age 69, range 44-89) have been evaluated postoperatively clinically
      [Constant Score (CS)] and radiographically (mean FU 34; range 24-93 months). The
      type of primary treatment, the amount of a metaphyseal bone defect, the
      preoperative status of the rotator cuff, the number of previous operative
      interventions and the type of FS according to Boileau were analysed whether they
      are of influence for clinical outcome. The mean CS increased significantly from
      16.9 +/- 6.7 preoperatively to 54.1 +/- 15.7 points postoperatively. The CS of
      primary conservative treatment was significantly higher in comparison to primary
      operative treatment. Patients with a metaphyseal bone defect of more than 3 cm
      had significantly lower CS results. Degenerative changes of the teres minor
      muscle also had a significant negative influence on clinical results. Score
      results decreased with increasing number of previous operations. There were no
      significant difference in between patients classified as Boileau type I and II
      (category 1) compared to types III and IV (category 2). RSA significantly
      improved the clinical result. A metaphyseal bone defect and preoperative
      degeneration of the teres minor showed to be negative prognostic factors. Primary
      operative treatment and the number of previous operations also negatively
      influenced the clinical result.

PMID- 24682521
TI  - Past achievements, current status and future perspectives of studies on 3-hydroxy
      3-methylglutaryl-CoA synthase (HMGS) in the mevalonate (MVA) pathway.
AB  - KEY MESSAGE: HMGS functions in phytosterol biosynthesis, development and stress
      responses. F-244 could specifically-inhibit HMGS in tobacco BY-2 cells and
      Brassica seedlings. An update on HMGS from higher plants is presented. 3-Hydroxy
      3-methylglutaryl-coenzyme A synthase (HMGS) is the second enzyme in the
      mevalonate pathway of isoprenoid biosynthesis and catalyzes the condensation of
      acetoacetyl-CoA and acetyl-CoA to produce S-3-hydroxy-3-methylglutaryl-CoA (HMG
      CoA). Besides HMG-CoA reductase (HMGR), HMGS is another key enzyme in the
      regulation of cholesterol and ketone bodies in mammals. In plants, it plays an
      important role in phytosterol biosynthesis. Here, we summarize the past
      investigations on eukaryotic HMGS with particular focus on plant HMGS, its
      enzymatic properties, gene expression, protein structure, and its current status
      of research in China. An update of the findings on HMGS from animals (human, rat,
      avian) to plants (Brassica juncea, Hevea brasiliensis, Arabidopsis thaliana) will
      be discussed. Current studies on HMGS have been vastly promoted by developments
      in biochemistry and molecular biology. Nonetheless, several limitations have been
      encountered, thus some novel advances in HMGS-related research that have recently
      emerged will be touched on.

PMID- 24682524
TI  - Functional outcome and mortality in nonagenarians following hip fracture surgery.
AB  - INTRODUCTION: The world's population is ageing and the elderly population itself
      is growing older. This population shows a high incidence of hip fractures. We
      performed a retrospective study, reviewing the functional status, postoperative
      complications and mortality rate of nonagenarians who underwent surgery for hip
      fracture. METHODS AND SUBJECTS: 56 nonagenarian patients underwent hip fracture
      surgery in our institution between January 2000 and December 2010. Two of these
      patients had presented with hip fracture on separate occasions, giving a total of
      58 hips for analysis. Patients with open fracture, subtrochanteric fracture,
      polytrauma and pathological fracture were excluded. The case notes, electronic
      records and X-rays for all those included in the study were reviewed. The main
      outcome measures were functional status, postoperative complications and
      mortality rate at 1 year. RESULTS: Patients with extracapsular hip fractures were
      associated with higher risks of postoperative complications (60.7 %; p = 0.037),
      mortality (25 %; p = 0.003) and more likely to be non-ambulant at 1 year (53.6 vs
      16.7 %; p = 0.003). Females were more likely to suffer postoperative
      complications than males (p = 0.016). 46.6 % of the patients had immediate
      postoperative complications and most commonly due to urological complications
      (29.3 %). The 1-year mortality rate was 12.1 %. A notable proportion of patients
      (65.5 %) remained ambulant 1 year postoperatively, although almost half of the
      patients (48.3 %) who could ambulate independently pre-injury required a walking
      aid after hip fracture surgery. CONCLUSION: Nonagenarians have good surgical
      outcomes after hip fracture surgery with low mortality rate. They should be
      treated similarly as their younger counterparts in terms of decision for surgery.
      Potential decline in functional status and rehabilitation options should be
      shared with the patient and family at an early stage.

PMID- 24682522
TI  - Cosuppression of RBCS3B in Arabidopsis leads to severe photoinhibition caused by
      ROS accumulation.
AB  - KEY MESSAGE: Cosuppression of an Arabidopsis Rubisco small subunit gene RBCS3B at
      Arabidopsis resulted in albino or pale green phenotypes which were caused by ROS
      accumulation As the most abundant protein on Earth, Rubisco has received much
      attention in the past decades. Even so, its function is still not understood
      thoroughly. In this paper, four Arabidopsis transgenic lines (RBCS3B-7, 18, 33,
      and 35) with albino or pale green phenotypes were obtained by transformation with
      a construct driving expression of sense RBCS3B, a Rubisco small subunit gene. The
      phenotypes produced in these transgenic lines were found to be caused by
      cosuppression. Among these lines, RBCS3B-7 displayed the most severe phenotypes
      including reduced height, developmental arrest and plant mortality before
      flowering when grown under normal light on soil. Chloroplast numbers in mesophyll
      cells were decreased compared to WT, and stacked thylakoids of chloroplasts were
      broken down gradually in RBCS3B-7 throughout development. In addition, the RBCS3B
      7 line was light sensitive, and PSII activity measurement revealed that RBCS3B-7
      suffered severe photoinhibition, even under normal light. We found that
      photoinhibition was due to accumulation of ROS, which accelerated photodamage of
      PSII and inhibited the repair of PSII in RBCS3B-7.

PMID- 24682525
TI  - Autophagy may protect MC3T3-E1 cells from fluoride-induced apoptosis.
AB  - Fluoride is an essential trace element for all mammalian species; however, excess
      fluoride intake is known to be toxic to cells in animals and humans. The toxicity
      of fluoride is mainly exerted via induction of apoptosis. Autophagy is induced by
      numerous cytotoxic stimuli; however, it is often unclear whether, under specific
      conditions, autophagy has a pro-survival or a pro-apoptotic role. To answer this
      critical question, the present study assessed autophagy and apoptosis
      simultaneously in single cells. It was demonstrated that fluoride was able to
      inhibit cell proliferation and induce apoptosis and autophagy, whereas autophagy
      appeared to be protective. Further analysis revealed that MAPK/JNK-dependent
      autophagy may be protective in fluoride-induced apoptosis. It is anticipated that
      the presented single-cell approach may be a powerful tool for gaining a
      quantitative understanding of the complex regulation of autophagy, its effect on
      cell fate and its association with other cellular pathways. 

PMID- 24682526
TI  - MR imaging of the pelvis: a guide to incidental musculoskeletal findings for
      abdominal radiologists.
AB  - Occasionally patients who undergo magnetic resonance imaging for presumed pelvic
      disease demonstrate unexpected musculoskeletal imaging findings in the imaged
      field. Such incidental findings can be challenging to the abdominal radiologist,
      who may not be familiar with their appearance or know the appropriate diagnostic
      considerations. Findings can include both normal and abnormal bone marrow,
      osseous abnormalities such as Paget's disease, avascular necrosis, osteomyelitis,
      stress and insufficiency fractures, and athletic pubalgia, benign neoplasms such
      as enchondroma and bone island, malignant processes such as metastasis and
      chondrosarcoma, soft tissue processes such as abscess, nerve-related tumors, and
      chordoma, joint- and bursal-related processes such as sacroiliitis, iliopsoas
      bursitis, greater trochanteric pain syndrome, and labral tears, and iatrogenic
      processes such as bone graft or bone biopsy. Though not all-encompassing, this
      essay will help abdominal radiologists to identify and describe this variety of
      pelvic musculoskeletal conditions, understand key radiologic findings, and
      synthesize a differential diagnosis when appropriate.

PMID- 24682527
TI  - Socioeconomic inequalities in risk of hospitalization for community-acquired
      bacteremia: a Danish population-based case-control study.
AB  - In a Danish population-based case-control study, we examined the association
      between socioeconomic status (SES) and risk of community-acquired bacteremia, as
      well as the contribution of chronic diseases and substance abuse to differences
      in bacteremia risk. Analyses were based on 4,117 patients aged 30-65 years who
      were hospitalized with first-time community-acquired bacteremia during 2000-2008
      and 41,170 population controls matched by sex, age, and region of residence.
      Individual-level information on SES (education and income), chronic diseases, and
      substance abuse was retrieved from public and medical registries. Conditional
      logistic regression was used to compute odds ratios for bacteremia. Persons of
      low SES had a substantially higher risk of bacteremia than those of high SES (for
      short duration of education vs. long duration, odds ratio = 2.30 (95% confidence
      interval: 2.10, 2.52); for low income vs. high income, odds ratio = 2.77 (95%
      confidence interval: 2.54, 3.02)). A higher prevalence of chronic diseases and
      substance abuse in low-SES individuals versus high-SES individuals explained 43%
      48% of the socioeconomic differences in bacteremia risk. In a country with a
      universal welfare system, differences in the burden of chronic diseases and
      substance abuse seem to have major importance in explaining inequalities in
      bacteremia risk. 

PMID- 24682528
TI  - Assessing phenological change and climatic control of alpine grasslands in the
      Tibetan Plateau with MODIS time series.
AB  - The Tibetan Plateau, a unique cold and dry region recognized as the Earth's third
      pole, is primarily composed of alpine grasslands (>60 %). While a warming climate
      in the plateau is being recorded, phenology of alpine grasslands and its climatic
      dependencies are less investigated. This study tests the feasibility of the
      frequently observed Moderate Resolution Imaging Spectroradiometer (MODIS) time
      series (500 m, 8 days) in examining alpine phenology in the plateau. A set of
      phenological metrics are extracted from the MODIS Normalized Difference
      Vegetation Index (NDVI) series in each year, 2000-2010. A nonparametric Mann
      Kendall trend analysis is performed to find the trends of these phenological
      metrics, which are then linked to monthly climatic records in the growing season.
      Opposite trends of phenological change are observed between the east and west of
      the plateau, with delayed start of season, peak date, and end of season in the
      west and advanced phenophases in the east. The correlation analysis indicates
      that precipitation, with a decreasing trend in the west and increasing trend in
      the east, may serve as the primary driver of the onset and peak dates of
      greenness. Temperature increases all over the plateau. While the delay of the end
      of season in the west could be related to higher late-season temperature, its
      advance in the east needs further investigation in this unique cold region. This
      study demonstrates that frequent satellite observations are able to extract
      phenological features of alpine grasslands and to provide spatiotemporally
      detailed base information for long-term monitoring on the plateau under rapid
      climate change. 

PMID- 24682531
TI  - Treatment of complex atherosclerotic femoropopliteal artery disease with a self
      expanding interwoven nitinol stent: midterm results from the Leipzig SUPERA 500
      registry.
AB  - AIMS: To examine the efficacy and durability of an interwoven self-expanding
      nitinol stent in the treatment of complex femoropopliteal artery lesions in
      unselected patients. METHODS AND RESULTS: Five hundred and twenty-seven limbs in
      470 patients with femoropopliteal arterial disease were treated with SUPERA
      stents. Follow-up data were prospectively collected in a single-centre registry
      and were available for 439 patients (492 limbs). The patients were followed by
      Doppler ultrasound, stent roentgenograms, estimation of Rutherford-Becker class
      (RBC) and ankle-brachial index (ABI). Total occlusions were present in 277 limbs
      (52.6%) and 52.4% had either moderate or severe calcification. The mean lesion
      length was 126.4 mm. The primary patency (PP) rates were 83.3% after 12 months
      and 72.8% at two years. The secondary patency rates were 98.1% after 12 months
      and 92.0% at two years. Patency rates did not differ between superficial femoral
      artery (SFA) and popliteal lesions. Between baseline and a mean of 21 months of
      follow-up, mean ABI increased from 0.53 to 0.91, and mean RBC decreased from 3.0
      to 1.9 (p<0.001 for both comparisons). Radiographs performed on 229 patients at a
      mean of 16.6 months confirmed the absence of stent fractures in all patients.
      CONCLUSIONS: Over a two-year surveillance period, the patency rate and fracture
      resistance of SUPERA stents implanted for complex femoropopliteal artery disease
      were high.

PMID- 24682529
TI  - Antenatal depression case finding by community health workers in South Africa:
      feasibility of a mobile phone application.
AB  - Randomized controlled trials conducted in resource-limited settings have shown
      that once women with depressed mood are evaluated by specialists and referred for
      treatment, lay health workers can be trained to effectively administer
      psychological treatments. We sought to determine the extent to which community
      health workers could also be trained to conduct case finding using short and
      ultrashort screening instruments programmed into mobile phones. Pregnant, Xhosa
      speaking women were recruited independently in two cross-sectional studies (N =
      1,144 and N = 361) conducted in Khayelitsha, South Africa and assessed for
      antenatal depression. In the smaller study, community health workers with no
      training in human subject research were trained to administer the Edinburgh
      Postnatal Depression Scale (EPDS) during the routine course of their community
      based outreach. We compared the operating characteristics of four short and
      ultrashort versions of the EPDS with the criterion standard of probable
      depression, defined as an EPDS-10 >= 13. The prevalence of probable depression
      (475/1144 [42 %] and 165/361 [46 %]) was consistent across both samples. The 2
      item subscale demonstrated poor internal consistency (Cronbach's alpha ranged
      from 0.55 to 0.58). All four subscales demonstrated excellent discrimination,
      with area under the receiver operating characteristic curve (AUC) values ranging
      from 0.91 to 0.99. Maximal discrimination was observed for the 7-item depressive
      symptoms subscale: at the conventional screening threshold of >=10, it had 0.97
      sensitivity and 0.76 specificity for detecting probable antenatal depression. The
      comparability of the findings across the two studies suggests that it is feasible
      to use community health workers to conduct case finding for antenatal depression.

PMID- 24682530
TI  - Atypical teratoid rhabdoid tumor in the cavernous sinus of a toddler presenting
      with oculomotor nerve palsy.
AB  - INTRODUCTION: Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly
      malignant, and aggressive tumor of infancy. Although the prognosis of ATRT has
      been extremely poor, recently, the first prospective study for ATRT demonstrated
      improvement of prognosis. On the other hands, oculomotor nerve palsy is rare in
      children and the most frequent etiology is congenital. To our knowledge, only a
      few ATRT cases presenting with oculomotor nerve palsy have been reported, but
      ATRT originating from the cavernous sinus (CS) has not yet been reported. CASE
      REPORT: An 18-month-old girl with right oculomotor nerve palsy was admitted, and
      a small mass in the right CS was detected with brain MRI. Although she received
      steroid pulse therapy and antimicrobial therapy, the mass continued to enlarge.
      One month after admission, the mass was partially resected and diagnosed as ATRT.
      Multimodal therapy including anthracycline-based chemotherapy, intrathecal
      therapy, and cranial irradiation was performed. Twenty-nine months after
      resection, she was alive without tumor relapse, but the oculomotor nerve palsy
      persisted. CONCLUSION: This is the first reported case of ATRT located in the CS
      presenting with oculomotor nerve palsy. This case was successfully treated with
      partial removal of the tumor, a new chemotherapy regimen for ATRT and cranial X
      ray irradiation.

PMID- 24682533
TI  - Should medical students be taught alternative medicine?

PMID- 24682534
TI  - Size-dependent enhancement of water relations during post-fire resprouting.
AB  - In resprouting species, fire-induced topkill causes a reduction in height and
      leaf area without a comparable reduction in the size of the root system, which
      should lead to an increase in the efficiency of water transport after fire.
      However, large plants undergo a greater relative reduction in size, compared with
      small plants, so we hypothesized that this enhancement in hydraulic efficiency
      would be greatest among large growth forms. In the ecotone between long-leaf pine
      (Pinus palustris Mill.) savannas and wetlands, we measured stomatal conductance
      (gs), mid-day leaf water potential (Psileaf), leaf-specific whole-plant hydraulic
      conductance (KL.p), leaf area and height of 10 species covering a range of growth
      forms in burned and unburned sites. As predicted, KL.p was higher in post-fire
      resprouts than in unburned plants, and the post-fire increase in KL.p was
      positively related to plant size. Specifically, large-statured species tended to
      undergo the greatest relative reductions in leaf area and height, and
      correspondingly experienced the greatest increases in KL.p. The post-fire
      increase in KL.p was smaller than expected, however, due to a decrease in
      absolute root hydraulic conductance (i.e., not scaled to leaf area). The higher
      KL.p in burned sites was manifested as an increase in gs rather than an increase
      in Psileaf. Post-fire increases in gs should promote high rates of photosynthesis
      for recovery of carbohydrate reserves and aboveground biomass, which is
      particularly important for large-statured species that require more time to
      recover their pre-fire size. 

PMID- 24682532
TI  - The impact of 5-formyltetrahydrofolate on the anti-tumor activity of
      pralatrexate, as compared to methotrexate, in HeLa cells in vitro.
AB  - PURPOSE: To investigate the impact of 5-formyltetrahydrofolate on the activities
      of pralatrexate, as compared to methotrexate (MTX), in vitro. METHODS: Cells were
      exposed to (6S)5-formyltetrahydrofolate (5-formylTHF) for 24 h, before or after a
      6-h exposure to antifolates following which the cellular accumulation and
      activities of the drugs were evaluated in HeLa cells. RESULTS: A 24-h delay
      between a 6-h exposure to antifolates and a subsequent 24-h exposure to 4 MUM 5
      formylTHF sustained the full activities of both antifolates. A 72-h interval was
      required between a single exposure of up to 4 MUM 5-formylTHF and subsequent
      exposure to drugs to sustain activities of the antifolates. When cells were
      incubated with 4 MUM 5-formylTHF for 24 h weekly, for 4 weeks, there was no
      significant increase in the IC50 for pralatrexate, but the MTX IC50 increased 2.5
      fold as compared to cells growing continuously in 25 nM 5-formylTHF. This
      cyclical exposure to 5-formylTHF increased the cell folate pool by 16 %, had no
      significant effect on the intracellular pralatrexate level, but decreased
      intracellular MTX by 15 %. An extracellular concentration of MTX 50-fold higher
      than that of pralatrexate was required to achieve an intracellular level, and
      growth inhibition, comparable to that of pralatrexate. CONCLUSIONS: Cyclical
      exposures to 5-formylTHF at levels in excess of what is achieved in most clinical
      "rescue" regimens do not affect pralatrexate accumulation nor antitumor activity
      in HeLa cells, in contrast to MTX. An important element in preserving
      pralatrexate activity is achieving a sufficient interval between exposure to 5
      formylTHF and the next dose of antifolate.

PMID- 24682535
TI  - Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to
      neuropathy susceptibility in type 2 diabetes.
AB  - Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) are
      common type 2 diabetes complications with a large inter-individual variability in
      terms of clinical manifestations and severity. Our aim was to evaluate a possible
      involvement of genetic polymorphisms in miRNA regions in the susceptibility to
      DPN and CAN. Nine polymorphisms in miRNA genes were studied in a sample of 132
      type 2 diabetes patients (T2D) analysed for DPN and 128 T2D patients analysed for
      CAN. A genotype-phenotype correlation analysis was performed. The T allele of
      rs11888095 single nucleotide polymorphism (SNP) in MIR128a was significantly
      associated with a higher risk (ORadj = 4.89, P adj = 0.02), whereas the C allele
      of rs2910164 SNP in MIR146a was associated with a lower risk to develop DPN
      (ORadj = 0.49, P adj = 0.09), respectively. A multivariate logistic regression
      analysis confirmed that both SNPs contribute to DPN (p < 0.001 and p = 0.01 for
      MIR128a and MIR146a, respectively). MIR128a SNP significantly contributed also to
      DPN score (p = 0.026). Rs895819 SNP in MIR27a was significantly associated with a
      higher risk to develop early CAN (P adj = 0.023 and ORadj = 3.43). The rs2910164
      SNP in MIR146a showed a protective effect respect to early CAN (P adj = 0.052,
      ORadj = 0.32) and to confirmed CAN (P adj = 0.041, ORadj = 0.13). The same SNP
      resulted significantly associated with a lower CAN score and a higher E/I (p =
      0.002 and p = 0.003, respectively). In conclusion, we described associations of
      MIR128a and MIR146a SNPs with DPN susceptibility and of MIR146a and MIR27a SNPs
      with CAN susceptibility. This is the first study showing that genetic variability
      in miRNA genes could be involved in diabetic neuropathies susceptibility. 

PMID- 24682536
TI  - Are frequency and severity of sleep-disordered breathing in obese children and
      youth with and without type 2 diabetes mellitus different?
AB  - Obstructive sleep apnea (OSA) is a risk factor for insulin resistance and type 2
      diabetes mellitus (T2DM) in adults. Data in children are limited. The aim was to
      study the frequency and severity of OSA and its association with cardiometabolic
      risk factors in obese children and adolescents with and without T2DM. In this
      prospective cross-sectional study, obese children and adolescents with and
      without T2DM underwent polysomnography and blood tests for fasting lipids,
      insulin, glucose, liver functions, and C-reactive protein. All participants
      completed a questionnaire on past and present sleep-disordered breathing (SDB).
      Results were compared between T2DM and obese non-diabetic controls matched for
      body mass index-standard deviation score (BMI-SDS) and also according to the
      glycemic status: T2DM, impaired glucose tolerance (IGT), and normal glycemic
      control. Eleven patients with T2DM (age 15.9 +/- 3.6 years) and 30 BMI-SDS
      matched non-diabetic subjects (age 12.7 +/- 3.0 years) were studied. Among the
      entire cohort, 45 % had a history of snoring, 26 % reported apneic episodes
      during sleep, and 65 % had daytime fatigue. There were no significant between
      group differences in SDB history or abnormal polysomnographic results [apnea
      hypopnea index (AHI) >5/h]. The percentage of subjects with AHI >5/h was 45.5 %
      in T2DM patients, 25 % in obese patients with IGT, and 18.2 % in obese patients
      without IGT, although the difference was not statistically significant (p =
      0.25). Plasma C-reactive protein levels were related to both glycemic status and
      OSA severity. The severity of OSA in obese children and adolescents is unrelated
      to the presence of diabetes. OSA may play a minor role in the development and
      progression of T2DM in children and adolescents. Further studies in larger
      cohorts are required. 

PMID- 24682537
TI  - Electrochemotherapy for the management of melanoma skin metastasis: a review of
      the literature and possible combinations with immunotherapy.
AB  - Despite surgical treatment of primary tumor, about 5-10 % of melanoma patients
      will eventually suffer from cutaneous or subcutaneous metastasis. The presence of
      skin metastases decreases patients' quality of life. Their management is a
      challenge and depends on several variables such as size and number of the
      lesions, their location, the presence or absence of visceral metastasis. When
      possible, radical surgical resection is the best approach; if surgery is not
      expected to provide a reasonable functional outcome, alternative treatments must
      be considered. Several local and loco-regional treatments, such as
      electrochemotherapy and regional chemotherapy, are available for the management
      of melanoma skin metastasis. Even if high response rates have been observed in
      several clinical trials, their impact on survival is not clear. Efforts are being
      made to improve their efficacy and minimize toxicity. The combination of such
      treatments with immunotherapy could be a strategy to induce durable responses and
      improve survival. In fact, regionally treated patients do not have the immune
      suppression associated with most systemic treatments, which could compromise the
      efficacy of immunotherapy, and recent findings suggest that the inflammatory
      reactions following loco-regional cytotoxic treatments, such as
      electrochemotherapy, may enhance the activity of immunotherapeutic agents. In
      this manuscript, we review recent studies on electrochemotherapy and melanoma
      skin metastasis, and we comment about the role that combinations with
      immunotherapy may have based on the data provided by clinical trials and
      translational research.

PMID- 24682538
TI  - Immunomodulatory activity of commonly used drugs on Fc-receptor-mediated human
      natural killer cell activation.
AB  - Natural killer (NK) cells mediate defense against neoplastic as well as infected
      cells. Yet, how their effector functions are affected by the large variety of
      pharmacological compounds commonly in use has not been investigated
      systematically. Here, we screened 1,200 in-use or previously approved drugs for
      their biological effect on freshly isolated human peripheral blood-derived NK
      cells. Mimicking antibody-dependent cellular cytotoxicity (ADCC), known to be
      important in antibody-based immunotherapies against, e.g., human malignancies,
      the cells were stimulated by Fc-receptor (CD16) engagement. Cellular responses
      were assessed by flow cytometry. Fifty-six compounds that significantly inhibited
      and twelve that enhanced one or more of the readouts of adhesion, exocytosis, and
      chemokine production were identified and confirmed as hits. Among the confirmed
      inhibitors, 80 % could be assigned to one of seven major pharmacological classes.
      These classes were beta2-adrenergic agonists, prostaglandins, phosphodiesterase-4
      inhibitors, Ca(2+)-channel blockers, histamine H1-receptor antagonists,
      serotonin/dopamine receptor antagonists, and topoisomerase inhibitors that
      displayed distinct inhibitory patterns on NK cell responses. Among observed
      enhancers, interestingly, two ergosterol synthesis inhibitors were identified
      that specifically promoted exocytosis. In summary, these results provide a
      comprehensive knowledge base of the effect known drugs have on NK cells. More
      specifically, they provide an overview of drugs that may modulate NK cell
      mediated ADCC in the context of clinical immunotherapies.

PMID- 24682539
TI  - Caloric restriction maintains OX40 agonist-mediated tumor immunity and CD4 T cell
      priming during aging.
AB  - Immune responses wane during aging, posing challenges to the potential
      effectiveness of cancer immunotherapies. We previously demonstrated that in the
      context of a promising immunotherapeutic, OX40 agonist (alphaOX40), older animals
      exhibited impaired anti-tumor immune responses and diminished CD4 T cell effector
      differentiation. In this study, we hypothesized that tumor immune responses could
      be maintained during aging through caloric restriction (CR) or dietary
      supplementation with resveratrol (RES), a CR mimetic. Mice were placed on either
      a calorically restricted diet or a RES-formulated diet starting between 4 and 6
      months of age and continued until mice reached 12 months of age. Tumor immune
      responses were assessed after challenging with either sarcoma or breast tumor
      cells followed by alphaOX40 treatment. Our results show that CR, but not RES,
      maintained OX40-mediated anti-tumor immunity. In addition, CR fully sustained
      antigen-specific CD4 T cell priming in aged hosts (12 months old), whereas tumor
      specific CD8 T cell priming was not fully maintained compared to young reference
      animals (2 months old). Thus, CR appears to maintain immunological fitness of the
      CD4 T cell priming environment during aging, which is critical for optimal OX40
      mediated responses.

PMID- 24682540
TI  - Association between recurrent aphthous stomatitis and Helicobacter pylori
      infection: a meta-analysis.
AB  - OBJECTIVES: Several studies have shown the possible involvement of Helicobacter
      pylori infection in individuals with recurrent aphthous stomatitis (RAS), but the
      relationship remains controversial. This meta-analysis was performed to validate
      the association between RAS and H. pylori infection. MATERIALS AND METHODS: The
      PubMed database was searched up to January 25, 2013 to select studies on the
      prevalence of H. pylori infection between RAS patients and control subjects.
      Studies were included if they evaluated and clearly defined exposure to RAS,
      reported the incidence of H. pylori infection, or provided data for their
      estimation. For subgroup analyses, studies were separated by region, publication
      year, and source of controls to screen the potential factors against the results.
      Before meta-analysis, the studies were evaluated for publication bias and
      heterogeneity. Summary odds ratio (OR) estimates with 95 % confidence intervals
      (CIs) were calculated using the fixed-effects model. RESULTS: Seven case-control
      studies containing 339 cases and 271 controls were eventually selected for
      analysis. A total of 100 (29.50 %) RAS patients had H. pylori infection, which
      was significantly greater than the 54 (19.93 %) non-RAS controls with H. pylori
      infection (OR = 1.85, 95 % CI: 1.24-2.74, P = 0.002). This result persisted in a
      hospital-based control subgroup (OR = 2.72, 95 % CI: 1.57-4.72). CONCLUSIONS:
      Based on our meta-analysis, H. pylori infection is associated with an increased
      risk of RAS. CLINICAL RELEVANCE: The eradication of H. pylori in the stomach may
      promote relief of RAS symptoms and healing of oral ulcers, and even prevent the
      occurrence of RAS.

PMID- 24682544
TI  - Implementation practices in school health promotion: findings from an Austrian
      multiple-case study.
AB  - Since the 1980s, schools have been recognized as an ideal setting to promote
      students' and teachers' health. Three decades after the development of the Health
      Promoting Schools (HPS) approach, however, there is still only limited knowledge
      about the implementation of health promotion (HP) activities in this setting.
      Some studies indicate that schools change original concepts significantly when
      adapting them to local context in the course of implementation. In this paper, we
      pursue the question how HP is practiced in schools that have agreed to implement
      HPS concepts from regional service providers (SPs), using data from a multiple
      case study conducted in an Austrian province. Furthermore, we explored the HP
      activities chosen for implementation and the decision-making leading to their
      implementation. We draw on 22 interviews with members of the school community and
      provincial HP SPs, 9 group discussions, and 10 observations we have carried out
      within three schools between November 2010 and January 2012, supplemented by a
      variety of documents. We have identified 40 different HP activities, of which
      most targeted students, while mostly focusing on physical activity and/or
      psychosocial health. Planning, coordination and cooperation at the school level
      were minimal. Decisions for or against activities were seldom taken together, but
      taken individually due to personal knowledge, interests and experiences,
      perceived needs and problems, already existing activities and external
      influences. The findings suggest that schools rather remain with a traditional
      topic-based approach instead of realizing an integrated whole-school approach and
      indicate a need for more support especially during the early phases of
      implementation.

PMID- 24682541
TI  - A comprehensive catalogue and classification of human thermal climate indices.
AB  - The very large number of human thermal climate indices that have been proposed
      over the past 100 years or so is a manifestation of the perceived importance
      within the scientific community of the thermal environment and the desire to
      quantify it. Schemes used differ in approach according to the number of variables
      taken into account, the rationale employed, the relative sophistication of the
      underlying body-atmosphere heat exchange theory and the particular design for
      application. They also vary considerably in type and quality, as well as in
      several other aspects. Reviews appear in the literature, but they cover a limited
      number of indices. A project that produces a comprehensive documentation,
      classification and overall evaluation of the full range of existing human thermal
      climate indices has never been attempted. This paper deals with documentation and
      classification. A subsequent report will focus on evaluation. Here a
      comprehensive register of 162 thermal indices is assembled and a sorting scheme
      devised that groups them according to eight primary classification classes. It is
      the first stage in a project to organise and evaluate the full range of all human
      thermal climate indices. The work, when completed, will make it easier for users
      to reflect on the merits of all available thermal indices. It will be simpler to
      locate and compare indices and decide which is most appropriate for a particular
      application or investigation. 

PMID- 24682543
TI  - Impact of everolimus blood concentration on its anti-cancer activity in patients
      with metastatic renal cell carcinoma.
AB  - PURPOSE: Everolimus has demonstrated its efficacy in metastatic renal cell
      carcinoma (mRCC). Preliminary studies have shown high variability of everolimus
      blood concentrations (EBC). In other settings, its activity was correlated with
      EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess
      its influence on oncologic outcomes. PATIENTS AND METHODS: Our study analyzed
      first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic
      centers between March 2010 and August 2013. Patients presented a histologically
      confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies.
      RESULTS: Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The
      median trough concentration was 14.1 MUg/L (range 2.6-91.5). Fourteen patients
      (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 MUg/L were
      free from progression at 6 months (p = 0.06). Median progression-free survival
      was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median
      overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p =
      0.24), for patients above or below the median value of trough concentrations,
      respectively. CONCLUSION: Impact of drug exposure for AA tyrosine kinase
      inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC
      variability was confirmed in the present study, and the results suggest a
      relationship between initial EBC within the first 3 months and the drug activity.
      It underlines the need to prospectively include EBC monitoring in future clinical
      trials to determine the need of its implementation in routine use.

PMID- 24682545
TI  - Health-promoting residential aged care: a pilot project in Austria.
AB  - Long-term care for the aged is an area that has not been in the focus of health
      promotion so far. The paper describes context, concept and project plan of a 2
      year pilot project of comprehensive health-promoting setting development in
      residential aged care in Austria, and provides an overview over main experiences
      and results. Austria's most relevant health promotion agencies, a specialized
      scientific institute and Austria's largest provider of aged care acted as
      partners. The project aimed at developing elements of a comprehensive approach,
      but also providing evidence for the effectiveness of health promotion. Therefore,
      the project combined an organizational development approach with a scientific,
      randomized controlled study on mobility enhancement for residents. A
      comprehensive settings approach turned out acceptable for the main stakeholders
      of aged care (owners and management, staff, residents and residents' relatives).
      Strategy development, based on a systematic needs assessment, found staff health
      to be of special interest for the organization (ergonomics, workability over life
      course), and residents' relatives, got more attention. The mobility study was
      able to achieve positive results on occupational performance, concerning quality
      of-life indicators and reached also formerly inactive groups. After the end of
      the project, health promotion is still on the agenda of the organization; further
      developments will be monitored. Good support from the policy level and well
      established networking between the aged care provider, health promotion agencies
      and a network for health promotion in health care seems to have been an important
      resource for success. 

PMID- 24682548
TI  - The young neurosurgeon.

PMID- 24682549
TI  - Three-dimensional quantitative coronary angiography and quantification of
      jeopardised myocardium to predict functional significance of intermediate
      coronary artery stenosis.
AB  - AIMS: Despite the fact that fractional flow reserve (FFR) is better than
      angiography in guiding PCI, in the real world the choice to perform PCI is
      generally based on angiography. Three-dimensional quantitative coronary
      angiography (3D-QCA) may increase the accuracy of angiography, especially in
      intermediate coronary artery stenosis (ICAS). The aim of the study was to assess
      the best cut-off values of area stenosis % (AS%) and the extent of jeopardised
      myocardium for predicting FFR and for excluding the need to perform FFR. METHODS
      AND RESULTS: FFR, AS% and Myocardial Jeopardy Index (MJI) were assessed in 211
      ICAS. MJI (=-0.36; p=0.001), AS% (=-0.35; p=0.001) and presence of a chronic
      total occlusion (CTO) (=-0.15; p=0.01) were independent predictors of FFR. In
      patients without CTO (174 lesions), the best cut-offs for the detection of FFR
      <=0.80 for AS% and MJI were 61% (AUC=0.76; p<0.001) and 30% (AUC=0.71; p<0.001),
      respectively. More importantly, the cut-offs of AS% safely to exclude (100%
      sensitivity) an FFR <=0.80 were 40% (AUC=0.85, p<0.001) for an MJI >=30% and 50%
      (AUC=0.70, p<0.04) for an MJI <30%, respectively. CONCLUSIONS: AS%, MJI and the
      presence of a CTO predicted FFR values. 3D-QCA in addition to MJI allows the safe
      exclusion of FFR <=0.80, limiting FFR assessment to doubtful cases with
      considerable reduction of costs.

PMID- 24682550
TI  - Assessment of tubular reabsorption of phosphate as a surrogate marker for
      phosphate regulation in chronic kidney disease.
AB  - BACKGROUND/AIMS: Fibroblast growth factor 23 (FGF23) and soluble alpha-Klotho are
      emerging potential biomarkers of phosphorus and vitamin D metabolism which change
      in concentration in early chronic kidney disease (CKD) in order to maintain
      normal phosphorus levels. Tubular reabsorption of phosphate (TRP) has been
      commonly used to assess renal tubular phosphate transport. The aim of this study
      was to evaluate the usefulness of TRP as a surrogate marker of parameters of CKD
      mineral bone disease (CKD-MBD) in CKD. METHODS: A cross-sectional study was
      performed in 93 stable patients with predialysis CKD stage 1-5. In all patients,
      TRP, estimated glomerular filtration rate (eGFR), calcium, phosphate, intact
      parathyroid hormone (iPTH), 25-hydroxyvitamin D, serum FGF23 and urine soluble
      alpha-Klotho levels were measured. RESULTS: As renal function declined, TRP
      significantly decreased (P < 0.001; r = 0.763) and both iPTH and serum FGF23
      increased (P < 0.001; r = -0.598, P < 0.001; r = -0.453, respectively). The
      prevalence of hyperphosphatemia, secondary hyperparathyroidism, FGF23 excess and
      abnormal TRP increased progressively with declining eGFR. Although TRP level
      changed later than FGF23, abnormal levels of both TRP and FGF23 were observed
      earlier than changes in iPTH and serum phosphate. Decreased TRP was found to be
      independently associated with decreased eGFR and increased iPTH but was not
      associated with urine soluble alpha-Klotho or serum FGF23 level in multiple
      linear regression analysis. CONCLUSION: TRP is a simple, useful and cost-saving
      surrogate marker of the assessment of altered mineral metabolism in CKD patients
      and can be used as an alternative to serum FGF23, especially for mild to moderate
      renal insufficiency.

PMID- 24682551
TI  - Preparation of forefinger's sequence on keyboard orients ocular fixations on
      computer screen.
AB  - This study examined the links between attention, hand movements and eye movements
      when performed in different spatial areas. Participants performed a visual search
      task on a computer screen while preparing to press two keyboard keys sequentially
      with their index. Results showed that the planning of the manual sequence
      influenced the latency of the first saccade and the placement of the first
      fixation. In particular, even if the first fixation placement was influenced by
      the combination of both components of the prepared manual sequence in some
      trials, it was affected principally by the first component of the prepared manual
      sequence. Moreover, the probability that the first fixation placement did reflect
      a combination of both components of the manual sequence was correlated with the
      speed of the second component. This finding suggests that the preparation of the
      second component of the sequence influence simultaneous oculomotor behavior when
      motor control of the manual sequence relied on proactive motor planning. These
      results are discussed taking into account the current debate on the eye/hand
      coordination research. 

PMID- 24682552
TI  - [Not Available].

PMID- 24682553
TI  - [Not Available].
AB  - The paper examines the correlation between sociocultural factors and pain
      perception. During the 17th century the basis for the modern understanding of
      pain was laid; pain became a physically determined phenomenon. Around the middle
      of the 19th century new methods were developed to deaden and anaesthetize pain.
      Since then, the interpretation and understanding of pain has been dominated by
      medical views. Sociocultural influences, which up to that time played an
      important role in dealing with pain, were pushed into the background. Yet,
      ethnological studies reveal impressive diversity in coping with pain. Pain
      perception and pain response is influenced by physical, psychological as well as
      cultural factors. 

PMID- 24682554
TI  - [Not Available].
AB  - Complementary therapies are widely used and play an important role in the
      treatment of chronic pain syndromes. This review summarizes the evidences from
      randomized controlled trials for the effectiveness of a number of complementary
      therapies in migraine prophylaxis. The largest number of studies (a total of 15)
      is available for acupuncture. These studies are very heterogeneous in respect to
      interventions, methodological quality and outcome measurement, and the results
      are partly contradictory. The majority of trials, however, suggests that
      acupuncture is effective in migraine prophylaxis. The four existing, randomized
      and placebo-controlled trials on individualized homeopathy have shown conflicting
      results; clearly positive results have been reported only in the oldest,
      qualitatively least convincing study. Concerning herbal medicines the evidence is
      promising for extracts from Tanacetum parthenium (feverfew, five trials) and
      Petasites hybridus (one trial). Randomized trials on spinal manipulation for
      migraine prophylaxis have shown contradictory results. For neural therapy or
      complex strategies combining several complementary therapies only uncontrolled
      studies could be identified. In summary, there is promising evidence for the
      effectiveness of a number of complementary treatment options in migraine
      prophylaxis. Further research is clearly warranted. 

PMID- 24682555
TI  - [Not Available].
AB  - Adolescents often suffer from psychosocial and psychosomatic problems. In
      addition, a number of questions and uncertainties regarding health matters arise
      in the course of the gradual transition from childhood to adulthood. However,
      young people show great inhibitions towards psychosocial and medical consultation
      services. The establishment of an easily accessible consultation service at
      school thus might aid existing health promotion and disease prevention programs
      for young people. Using the example of a grammar school in Berlin, the demand for
      and the interest of the students in such a consultation service were examined on
      the basis of gender, age and types of subjective feeling of well-being regarding
      health (quantitatively). In addition, the best way to organise such a service was
      analysed (qualitatively). Significant differences in the demand for a
      consultation services are ascertained based on gender, age and subjective
      feelings of well-being regarding health. The interest in consultation services
      offered in school by an external specialist is greater among the older students,
      while the younger ones prefer lessons to deal with health topics. Regarding the
      organisation of a consultation service, it is important to the students that it
      remains anonymous and is open to all the problems and questions young people
      have. 

PMID- 24682556
TI  - [Not Available].
AB  - Based on the Federal Health Survey from 1998, the Augsburg heart attack registry,
      and the ninth coordinated population prediction, we have estimated the occurrence
      of heart attacks in Germany up to the year 2050. From the mere demographic
      perspective - regardless of medical and social influences - we can expect that
      the need for cardiac care will increase considerably. If we assume that the risk
      or the frequency of having a heart attack will remain the same, then the number
      of heart attacks in people aged 25 to over 90 and 35 to under 90 will increase,
      although the population size of these age groups will decline. The population
      over 75 years of age will with certainty determine the course of the incidence
      and prevalence of heart attacks. In addition to standardised incidence and/or
      prevalence rates, estimations of the absolute number of incidents and/or
      prevalent cases of the respective target illness have to be included in morbidity
      predictions in order to avoid misinterpretations. 

PMID- 24682558
TI  - [Not Available].

PMID- 24682559
TI  - [Not Available].

PMID- 24682557
TI  - [Not Available].
AB  - Allogeneic stem cell transplantation (alloSCT) is increasingly used in the
      treatment of hematological disorders. In order to demonstrate the national
      development of alloSCT as well as the effect of the foundation of local
      transplant centers, data of all alloSCT performed on patients living in
      Mecklenburg-Vorpommern (MV) during 1991 and 2000 were evaluated regarding date
      and location of the alloSCT, diagnosis and age of the patient as well as donor
      type. AlloSCT in patients from MV increased 6 fold from 1991 n=5 to 2000 n=30.
      Because of the lack of local transplant centers during the period between 1991
      and 1997, alloSCT of patients from MV were exclusively performed in other
      locations, whereas in 2000 only 2 of 30 alloSCT were performed in transplants
      centers outside MV. With the establishment of local centers, the gap between the
      numbers of alloSCT between MV and Germany was closed (1991 Germany 4,17/Million
      inhabitants, MV 2,67/Million inhabitants, 2000 Germany 17,4/Million inhabitants,
      MV 16,7/Million inhabitants). The increase in the number of alloSCT was mainly
      due to an increased use of unrelated stem cell donors which increased from n=0 in
      1991 to 12 out of 30 in 2000. Another important factor was the increase in the
      age limit with a mean age of 32 years in 1991 and 43 years in 2000 (upper range
      60 years). CONCLUSION: The data reflect the dramatic increase in alloSCT during
      the last decade caused by factors listed above. In addition, the development of
      the numbers of transplants of patients in MV supports the need for local
      transplant centers, since with the opening of local transplant centers the
      difference of the frequency of alloSCT between Germany and MV was completely
      eradicated.

PMID- 24682560
TI  - [Not Available].

PMID- 24682561
TI  - [Not Available].

PMID- 24682562
TI  - [Not Available].

PMID- 24682563
TI  - Is routine preoperative screening echocardiogram indicated in all children with
      congenital duodenal obstruction?
AB  - INTRODUCTION: Congenital duodenal obstruction (DO) is frequently associated with
      congenital heart disease (CHD). Operative repair of DO is often postponed until
      an echocardiogram is completed, which may result in unnecessary delays. We aimed
      to identify and characterize CHD in children with DO to determine if
      appropriately selected patients could forego preoperative echocardiogram.
      METHODS: A two-center retrospective review of all infants with DO undergoing
      operative repair with completed echocardiograms was included (2003-2011).
      Demographics, co-morbid conditions, clinical exam findings, radiologic imaging,
      and need for cardiac surgery were recorded. RESULTS: 67 children were identified.
      47 (70.1%) had CHD on echocardiogram of which 19 (40.5%) had significant CHD.
      Children without clinical findings, abnormalities on physical examination, and/or
      abnormal chest x-ray were unlikely to have CHD; i.e., no asymptomatic child had
      significant CHD. Sensitivity and specificity of clinical findings, physical exam,
      and/or chest x-ray for significant CHD were 100% (95% CI 0.79-1.0) and 37.5% (95%
      CI 0.24-0.53), respectively, for major CHD and 87.2% (0.74-0.95) and 60% (0.36
      0.80) for any CHD. CONCLUSION: Careful clinical assessment, evaluation with pulse
      oximetry, and chest x-ray may be sufficient to exclude significant CHD in
      children with DO. Identifying children at low risk for cardiac lesions may
      prevent unnecessary delays to operative intervention and may limit medical
      expenses.

PMID- 24682565
TI  - Giant pilomatrixoma of the right arm.

PMID- 24682564
TI  - Cell cycle analysis can differentiate thin melanomas from dysplastic nevi and
      reveals accelerated replication in thick melanomas.
AB  - Cell replication integrates aberrations of cell cycle regulation and diverse
      upstream pathways which all can contribute to melanoma development and
      progression. In this study, cell cycle regulatory proteins were detected in situ
      in benign and malignant melanocytic tumors to allow correlation of major cell
      cycle fractions (G1, S-G2, and G2-M) with melanoma evolution. Dysplastic nevi
      expressed early cell cycle markers (cyclin D1 and cyclin-dependent kinase 2;
      Cdk2) significantly more (p < 0.05) than common nevi. Post-G1 phase markers such
      as cyclin A, geminin, topoisomerase IIalpha (peaking at S-G2) and aurora kinase B
      (peaking at G2-M) were expressed in thin (<=1 mm) melanomas but not in dysplastic
      nevi, suggesting that dysplastic melanocytes engaged in the cell cycle do not
      complete replication and remain arrested in G1 phase. In malignant melanomas, the
      expression of general and post-G1 phase markers correlated well with each other
      implying negligible cell cycle arrest. Post-G1 phase markers and Ki67 but none of
      the early markers cyclin D1, Cdk2 or minichromosome maintenance protein 6 (Mcm6)
      were expressed significantly more often in thick (>1 mm) than in thin melanomas.
      Marker expression did not differ between metastatic melanomas and thick
      melanomas, with the exception of aurora kinase A of which the expression was
      higher in metastatic melanomas. Combined detection of cyclin A (post-G1 phase)
      with Mcm6 (replication licensing) and Ki67 correctly classified thin melanomas
      and dysplastic nevi in 95.9 % of the original samples and in 93.2 % of cross
      validated grouped cases at 89.5 % sensitivity and 92.6 % specificity. Therefore,
      cell cycle phase marker detection can indicate malignancy in early melanocytic
      lesions and accelerated cell cycle progression during vertical melanoma growth.

PMID- 24682566
TI  - Sentinel lymph node mapping in endometrial cancer: a concept ready for clinical
      routine?

PMID- 24682567
TI  - Accumulation and localization of cadmium in potato (Solanum tuberosum) under
      different soil Cd levels.
AB  - Phytoavailability and uptake mechanism of Cd in edible plant tissues grown on
      metal polluted agricultural soils has become a growing concern worldwide. Uptake,
      transport, accumulation and localization of cadmium in potato organs under
      different soil Cd levels were investigated using inductively-coupled plasma mass
      spectrometry and energy dispersive X-ray microanalysis. Results indicated that Cd
      contents in potato organs increased with increasing soil Cd concentrations, and
      the order of Cd contents in different organs was leaves > stems/roots > tubers.
      Root-to-stem Cd translocation coefficients ranged from 0.89 to 1.81. Cd
      localization in potato tissues suggested that leaves and stems should be the main
      compartment of Cd storage and uptake. Although low concentrations of Cd migrated
      from the root to tuber, Cd accumulation in the tuber exceeded the standard for
      food security. Therefore, the planting of potato plants in farmland containing Cd
      should be closely evaluated due to its potential to present health risks.

PMID- 24682568
TI  - A Review of Current Evidence of Olmesartan Medoxomil Mimicking Symptoms of Celiac
      Disease.
AB  - Objective:To review the evidence of an association between olmesartan medoxomil
      and symptoms mimicking celiac disease.Data Sources:Literature was searched in
      PubMed (1965-November 2013) using the key words or MeSH terms olmesartan,
      enteropathy, celiac disease, sprue, and diarrhea. References from the Food and
      Drug Administration (FDA) and Dipiro's Pharmacotherapy eighth edition textbook
      were also reviewed.Data Synthesis:There have been recent implications of
      olmesartan medoxomil being linked to symptoms mimicking celiac disease.
      Investigators first identified the association in 22 patients who presented with
      presumed refractory celiac disease. Upon further evaluation, it was discovered
      that these symptoms improved when olmesartan was discontinued. In response to
      this report, additional case studies have been published. DeGaetani et al also
      further analyzed patients with seronegative villous atrophy from the Celiac
      Disease Center and found that olmesartan accounted for 22% of previously
      unclassified sprue cases. Conversely, the authors of the ROADMAP trial, which
      compared olmesartan to placebo, found no significant differences in the incidence
      of gastrointestinal adverse effects.Conclusions:There is growing evidence
      supporting the association between olmesartan and sprue-like symptoms; however,
      further research is warranted. These symptoms can be life threatening and
      clinicians should be aware of the potential association.

PMID- 24682569
TI  - Ventricular rate monitoring as a tool to predict and prevent atrial fibrillation
      related inappropriate shocks in heart failure patients treated with cardiac
      resynchronisation therapy defibrillators.
AB  - OBJECTIVE: Inappropriate implantable cardioverter defibrillators (ICD) therapies
      have been associated with multiple adverse effects, including worse quality of
      life and prognosis. We evaluated the possibility of predicting atrial
      fibrillation (AF)-related inappropriate ICD shocks through continuous monitoring
      of device diagnostics. METHODS: 1404 ICD patients were prospectively followed in
      an observational research by 74 Italian cardiology centres. Device diagnostics
      stored daily information on AF duration and ventricular rate (VR) during AF.
      Uncontrolled VR was defined as mean VR>80 beats per minute (bpm) and maximum
      VR>110 bpm. Expert electrophysiologists reviewed the ventricular
      tachycardia/ventricular fibrillation (VT/VF) episodes electrograms, stored in the
      device memory, and classified appropriate detections, inappropriate detection
      mechanisms and ICD therapy outcomes. RESULTS: Over a median follow-up of 31
      months, 511 (36%) patients suffered spontaneous VT/VF, which were treated by ICD
      shocks in a subgroup of 189 (13%) patients. Inappropriate detections occurred in
      232 (16%) patients, and inappropriate ICD shocks in 101 (7%) patients. AF was the
      cause of inappropriate shocks in 60 patients. AF caused 144 inappropriate shocks:
      53% of all inappropriate shocks. The likelihood of experiencing AF-related
      inappropriate shocks was 2.4% at 1 year and 6% at 5 years. Uncontrolled VR during
      AF proved to be an independent predictor of AF-related inappropriate shocks
      (OR=3.02, p=0.006); an alarm set at a VR>90 bpm or 100 bpm was associated with
      prediction of AF-related inappropriate shocks with a sensitivity of 73% or 62%,
      respectively. CONCLUSIONS: AF is the most common cause of inappropriate shocks in
      ICD patients. Continuous remote monitoring of VR during AF would promptly and
      efficiently predict AF-related inappropriate shocks. CLINICAL TRIAL REGISTRATION:
      http://clinicaltrials.gov/ct2/show/NCT01007474.

PMID- 24682570
TI  - Dimensionality of childhood psychopathology and the challenge of integration into
      clinical practice.

PMID- 24682571
TI  - Vertebral sarcoidosis: long-term follow-up with MRI.
AB  - Vertebral involvement in sarcoidosis is rare and its clinical and imaging
      features are non-specific. Indeed, because the lesions are hard to differentiate
      from metastatic disease based on imaging alone, a histological confirmation is
      advised. Fatty replacement is a well-known finding indicating stabilization and
      healing in both benign and malignant conditions. It can be used as an indicator
      of a favorable disease course and response to treatment. We report the case of a
      43-year-old woman with multifocal vertebral sarcoidosis lesions and long-term
      follow-up showing progressive and gradual fatty involution on magnetic resonance
      imaging (MRI) during 4 years of steroid treatment with a final favorable outcome.

PMID- 24682572
TI  - Positive clinical outcomes of the saphenous vein interposition technique for
      ruptured popliteal artery aneurysm.
AB  - PURPOSE: Popliteal artery aneurysms (PAAs) can be treated successfully by
      surgical and endovascular methods; however, the best treatment strategy for a
      ruptured PAA has yet to be established. We assessed the clinical results of using
      saphenous vein interposition to treat ruptured PAAs in our hospital. METHODS: The
      subjects of this study were seven men (average age 59 years, range 43-71 years),
      who underwent emergency surgery for a ruptured PAA at our hospital between
      January 2007 and November 2012. The patients were assessed after 1, 6, and 12
      months, postoperatively. RESULTS: All included patients underwent saphenous vein
      graft interposition via a medial approach. No complications or graft thromboses
      were encountered in the immediate postoperative period. The patients were
      discharged after an average of 4 days postoperatively (range 3-5 days). The
      patients were followed up for an average of 32 months (range 2-60 months). The
      medium-term graft patency was 100%. No patients suffered early or medium-term
      limb loss and there was no mortality. CONCLUSION: Based on our positive results,
      saphenous vein graft interposition should be considered as the first choice of
      surgical treatment for a ruptured PAA.

PMID- 24682573
TI  - Pharmacy study of natural health product adverse reactions (SONAR): a cross
      sectional study using active surveillance in community pharmacies to detect
      adverse events associated with natural health products and assess causality.
AB  - OBJECTIVES: To investigate the rates and causality of adverse event(s) (AE)
      associated with natural health product (NHP) use, prescription drug use and
      concurrent NHP-drug use through active surveillance in community pharmacies.
      DESIGN: Cross-sectional study of screened patients. SETTING: 10 community
      pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July
      2011. PARTICIPANTS: The participating pharmacy staff screened consecutive
      patients, or agents of patients, who were dropping or picking up prescription
      medications. PRIMARY OUTCOME MEASURES: Patients were screened to determine the
      proportions of them using prescription drugs and/or NHPs, as well as their
      respective AE rates. All AEs reported by the screened patients who took a NHP,
      consented to, and were available for, a detailed telephone interview (14%) were
      adjudicated fully to assess for causality. RESULTS: Over a total of 105 pharmacy
      weeks and 1118 patients screened, 410 patients reported taking prescription drugs
      only (36.7%; 95% CI 33.9% to 39.5%), 37 reported taking NHPs only (3.3%; 95% CI
      2.4% to 4.5%) and 657 reported taking prescription drugs and NHPs concurrently
      (58.8%; 95% CI 55.9% to 61.6%). In total, 54 patients reported an AE,
      representing 1.2% (95% CI 0.51% to 2.9%), 2.7% (95% CI 0.4% to 16.9%) and 7.3%
      (95% CI 5.6% to 9.6%) of each population, respectively. Compared with patients
      who reported using prescription drugs, the patients who reported using
      prescription drugs and NHPs concurrently were 6.4 times more likely to experience
      an AE (OR; 95% CI 2.52 to 16.17; p<0.001). Combined with data from Ontario,
      Canada, a national proportion was calculated, which found that 45.4% (95% CI
      43.8% to 47.0%) of Canadians who visit community pharmacies take NHPs and
      prescription drugs concurrently, and of those, 7.4% (95% CI 6.3% to 8.8%) report
      an AE. CONCLUSIONS: A substantial proportion of community pharmacy patients use
      prescription drugs and NHPs concurrently; these patients are at a greater risk of
      experiencing an AE. Active surveillance provides a means of detecting such AEs
      and collecting high-quality data on which causality assessment can be based.

PMID- 24682574
TI  - Mental health admissions in paediatric populations in North Wales: two cohorts
      compared 1875-1924 and 1994-2008.
AB  - OBJECTIVES: To investigate frequency of under-18s admitted to mental health
      services (MHS) in North West Wales (NWW) between 1875 and 2008. There are claims
      that 1 in 10 children have a mental illness, but there are little data on their
      inpatient MHS utilisation. SETTING: Looking at admissions at the secondary care
      level, three data samples were included; the first comprises historical asylum
      admissions, the second comprises contemporary admissions to acute psychiatric
      beds, and the third comprises admissions to district general hospital (DGH) beds
      that resulted in a mental health coding. PARTICIPANTS: All were under 18. There
      were 65 historical patients, 41 contemporary mental illness admissions and 943
      DGH admissions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome
      measures were diagnoses based on case notes of the historical cohort between 1875
      and 1924, as well as details of paediatric admissions to MHS from 1994 to 2008
      and paediatric admissions with a mental health component to the DGH in NWW.
      RESULTS: The incidence of admission to a mental health bed was 1.55 per year in
      the historical cohort compared with 2.9 in the contemporary. The overall
      incidence of admission to any bed in the contemporary cohort was 129 patients per
      year. There has been a twofold increase in the incidence of admissions for
      schizophrenia and related psychosis, but this most likely stems from an earlier
      age of admission rather than a true increase. CONCLUSIONS: There is a greater
      frequency of hospital admissions for youth under the age of 18 in NWW for mental
      health today than previously. The rates reported in the DGH sample are consistent
      with data from community surveys of patients meeting criteria for mental
      disorders and complement such data when it comes to planning for paediatric MHS.
      However, they also raise questions about the boundaries between disease and
      distress.

PMID- 24682575
TI  - Association of polypharmacy with fall-related fractures in older Taiwanese
      people: age- and gender-specific analyses.
AB  - OBJECTIVE: To elucidate the associations between polypharmacy and age- and gender
      specific risks of admission for fall-related fractures. DESIGN: Nested case
      control study. SETTING: This analysis was randomly selected from all elderly
      beneficiaries in 2007-2008, and represents some 30% of the whole older insurers
      using Taiwan's National Health Insurance Research Database. PARTICIPANTS: We
      identified 5933 cases newly admitted for fall-related fractures during 2007-2008,
      and 29 665 random controls free from fracture. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Polypharmacy was defined as the use of fall-related drugs of four or
      more categories of medications and prescribed related to fall within a 1-year
      period. Logistic regression models were employed to estimate the ORs and related
      95% CIs. The interaction of polypharmacy with age and sex was assessed
      separately. RESULTS: Compared with those who consumed no category of medication,
      older people who consumed 1, 2, 3 and >=4 categories of medications were all at
      significantly increased odds of developing fall-related fractures, with a
      significant dose-gradient pattern (beta=0.7953; p for trend <0.0001). There were
      significant interactions between polypharmacy and age, but no significant
      interactions between polypharmacy and gender. The dose-gradient relationship
      between number of medications category and risk of fall-related fractures was
      more obvious in women than in men (beta=0.1962 vs beta=0.1873). Additionally, it
      was most evident in older people aged 75-84 years (beta=0.2338). CONCLUSIONS:
      This population-based study in Taiwan confirms the link between polypharmacy and
      increased risk of fall-related fractures in older people; and highlights that
      elderly women and older people aged 75-84 years will be the targeted participants
      for further prevention from fall-related fractures caused by polypharmacy.

PMID- 24682577
TI  - The impact of funding deadlines on personal workloads, stress and family
      relationships: a qualitative study of Australian researchers.
AB  - OBJECTIVE: To examine the impact of applying for funding on personal workloads,
      stress and family relationships. DESIGN: Qualitative study of researchers
      preparing grant proposals. SETTING: Web-based survey on applying for the annual
      National Health and Medical Research Council (NHMRC) Project Grant scheme.
      PARTICIPANTS: Australian researchers (n=215). RESULTS: Almost all agreed that
      preparing their proposals always took top priority over other work (97%) and
      personal (87%) commitments. Almost all researchers agreed that they became
      stressed by the workload (93%) and restricted their holidays during the grant
      writing season (88%). Most researchers agreed that they submitted proposals
      because chance is involved in being successful (75%), due to performance
      requirements at their institution (60%) and pressure from their colleagues to
      submit proposals (53%). Almost all researchers supported changes to the current
      processes to submit proposals (95%) and peer review (90%). Most researchers (59%)
      provided extensive comments on the impact of writing proposals on their work life
      and home life. Six major work life themes were: (1) top priority; (2) career
      development; (3) stress at work; (4) benefits at work; (5) time spent at work and
      (6) pressure from colleagues. Six major home life themes were: (1) restricting
      family holidays; (2) time spent on work at home; (3) impact on children; (4)
      stress at home; (5) impact on family and friends and (6) impact on partner.
      Additional impacts on the mental health and well-being of researchers were
      identified. CONCLUSIONS: The process of preparing grant proposals for a single
      annual deadline is stressful, time consuming and conflicts with family
      responsibilities. The timing of the funding cycle could be shifted to minimise
      applicant burden, give Australian researchers more time to work on actual
      research and to be with their families.

PMID- 24682576
TI  - Acute hospital-based services utilisation during the last year of life in New
      South Wales, Australia: methods for a population-based study.
AB  - OBJECTIVES: The aim of this study is to describe healthcare utilisation in the
      last year of life for people in Australia, to help inform health services
      planning. The methods and datasets that are being used are described in this
      paper. DESIGN/SETTING: Linked, routinely collected administrative health data are
      being analysed for all people who died in New South Wales (NSW), Australia's most
      populous state, in 2007. The data comprised linked death records (2007), hospital
      admissions and emergency department presentations (2006-2007) and cancer
      registrations (1994-2007). PARTICIPANTS: There were 46 341 deaths in NSW in 2007.
      The initial analyses include 45 760 decedents aged 18 years and over. OUTCOME
      MEASURES: The primary measures address the utilisation of hospital-based services
      at the end of life, including number and length of hospital admissions, emergency
      department presentations, intensive care admissions, palliative-related
      admissions and place of death. RESULTS: The median age at death was 80 years.
      Cause of death was available for 95% of decedents and 85% were linked to a
      hospital admission record. In the greater metropolitan area, where data capture
      was complete, 83% of decedents were linked to an emergency department
      presentation. 38% of decedents were linked to a cancer diagnosis in 1994-2007.
      The most common causes of death were diseases of the circulatory system (34%) and
      neoplasms (29%). CONCLUSIONS: This study is among the first in Australia to give
      an information-rich census of end-of-life hospital-based experiences. While the
      administrative datasets have some limitations, these population-wide data can
      provide a foundation to enable further exploration of needs and barriers in
      relation to care. They also serve to inform the development of a relatively
      inexpensive, timely and reliable approach to the ongoing monitoring of acute
      hospital-based care utilisation near the end of life and inform whether service
      access and care are optimised.

PMID- 24682578
TI  - Hereditary apolipoprotein A1 amyloidosis with cutaneous and cardiac involvement:
      a long familial history.

PMID- 24682579
TI  - Pivotal roles for Streptomyces cell surface polymers in morphological
      differentiation, attachment and mycelial architecture.
AB  - Cells that are part of a multicellular structure are typically embedded in an
      extracellular matrix, which is produced by the community members. These matrices,
      the composition of which is highly diverse between different species, are
      typically composed of large amounts of extracellular polymeric substances,
      including polysaccharides, proteins, and nucleic acids. The functions of all
      these matrices are diverse: they provide protection, mechanical stability,
      mediate adhesion to surfaces, regulate motility, and form a cohesive network in
      which cells are transiently immobilized. In this review we discuss the role of
      matrix components produced by streptomycetes during growth, development and
      attachment. Compared to other bacteria it appears that streptomycetes can form
      morphologically and functionally distinct matrices using a core set of building
      blocks. 

PMID- 24682580
TI  - Frequency and correlates of suicidal ideation in pediatric obsessive-compulsive
      disorder.
AB  - This study examined the frequency and sociodemographic and clinical correlates of
      suicidal ideation in a sample of children and adolescents with obsessive
      compulsive disorder (OCD). Fifty-four youth with OCD and their parent(s) were
      administered the Schedule for Affective Disorders and Schizophrenia for School
      Age Children-Present and Lifetime, Children's Yale-Brown Obsessive Compulsive
      Scale, and Children's Depression Rating Scale-Revised. Children completed the
      Suicidal Ideation Questionnaire-Junior (SIQ-JR), Child Obsessive Compulsive
      Impact Scale-Child, and Multidimensional Anxiety Scale for Children; parents
      completed the Child Obsessive Compulsive Impact Scale-Parent, Swanson, Nolan, and
      Pelham-IV Parent Scale, and Young Mania Rating Scale-Parent Version. Seven youth
      endorsed clinically significant levels of suicidal ideation on the SIQ-JR.
      Suicidal ideation was significantly related to clinician-rated depressive
      symptoms, age, child-rated impairment and anxiety symptoms, and symmetry,
      sexuality/religiosity and miscellaneous symptom dimensions. There was no
      significant association between suicidal ideation and obsessive-compulsive
      symptom severity, comorbidity patterns, or several parent-rated indices (e.g.,
      impairment, impulsivity). These results provide initial information regarding the
      frequency and correlates of suicidal ideation in treatment-seeking youth with
      OCD. Clinical implications are discussed, as well as directions for future
      research. 

PMID- 24682581
TI  - Neuromuscular complications after hematopoietic stem cell transplantation.
AB  - PURPOSE: The aim of this study was to analyze the occurrence of neuromuscular
      symptoms in recipients of allogeneic hematopoietic stem cell transplantation
      (HSCT) for treatment of malignant hematopoietic disease. METHODS: Among 247
      outpatients after allogeneic HSCT, we conducted a prospective non-interventional
      study between July 2011 and August 2013. During follow-up visits, clinical and
      electrophysiological findings were correlated to the presence of
      autoantibodies/alloantibodies and to frequencies of lymphocyte subpopulations in
      peripheral blood. RESULTS: Resulting in an incidence of 8.1 %, 20 patients were
      diagnosed with neuromuscular complications at a median onset of 12 months post
      transplant. Five patients (25 %) were identified with polyneuropathy (PNP), ten
      patients (50 %) with combined PNP and myopathy, four patients (20 %) with
      myopathy or polymyositis (PM), and one patient (5 %) with myasthenia gravis (MG).
      Immune-mediated sensorimotor PNP after HSCT is characterized by a predominantly
      axonal lesion and can be overlapping with neurotoxic side effects. The latency
      between HSCT and development of PM varied between 60 days and 72 months. In
      general, PM occurs parallel to graft-versus-host disease (GvHD) after tapering of
      immunosuppressive medication. Typical clinical features are proximal bilateral
      limb weakness with muscle atrophy. Autoantibodies (Ab) were detected in 12
      patients, myositis-specific Ab only in one patient. In patients with progressive
      neurological symptoms, a decrease in the CD4/CD8 T cell ratio was observed.
      CONCLUSIONS: GvHD-related myositis appeared similar to idiopathic myositis
      regarding clinical and electromyographical findings. As outcome measure,
      sequential analysis of lymphocyte subpopulations in peripheral blood seems to be
      more suitable than Ab measurements. Whereas peripheral neuropathies are commonly
      observed shortly after HSCT, MG is a rare complication in the late post-HSCT
      phase.

PMID- 24682582
TI  - Epigallocatechin-3-gallate (EGCG) as a pro-osteogenic agent to enhance osteogenic
      differentiation of mesenchymal stem cells from human bone marrow: an in vitro
      study.
AB  - The proliferation and osteogenic capacity of mesenchymal stem cells (MSCs) needs
      to be improved for their use in cell-based therapy for osteoporosis. (-)
      Epigallocatechin-3-gallate (EGCG), one of the green tea catechins, has been
      widely investigated in studies of osteoblasts and osteoclasts. However, no
      consensus on its role as an osteogenic inducer has been reached, possibly because
      of the various types of cell lines examined and the range of concentrations of
      EGCG used. In this study, the osteogenic effects of EGCG are studied in primary
      human bone-marrow-derived MSCs (hBMSCs) by detecting cell proliferation, alkaline
      phosphatase (ALP) activity and the expression of relevant osteogenic markers. Our
      results show that EGCG has a strong stimulatory effect on hBMSCs developing
      towards the osteogenic lineage, especially at a concentration of 5 MUM, as
      evidenced by an increased ALP activity, the up-regulated expression of osteogenic
      genes and the formation of bone-like nodules. Further exploration has indicated
      that EGCG directes osteogenic differentiation via the continuous up-regulation of
      Runx2. The underlying mechanism might involve EGCG affects on osteogenic
      differentiation through the modulation of bone morphogenetic protein-2
      expression. EGCG has also been found to promote the proliferation of hBMSCs in a
      dose-dependent manner. This might be associated with its antioxidative effect
      leading to favorable amounts of reactive oxygen species in the cellular
      environment. Our study thus indicates that EGCG can be used as a pro-osteogenic
      agent for the stem-cell-based therapy of osteoporosis. 

PMID- 24682583
TI  - Neurobiology and treatment of adolescent female conduct disorder: FemNAT-CD
      consortium: a new European cooperation.

PMID- 24682584
TI  - Comparison of the early results of transanal hemorrhoidal dearterialization and
      hemorrhoidectomy using an ultrasonic scalpel.
AB  - PURPOSE: Doppler-guided transanal hemorrhoidal dearterialization and mucopexy
      (THD surgery) is a new approach for treating hemorrhoids. The early results of
      the procedure are presented and compared with those of hemorrhoidectomy using an
      ultrasonic scalpel (US surgery). METHODS: Thirty-six patients with grade III
      hemorrhoids underwent the THD surgery and were compared with a cohort of 30
      patients with grade III or IV hemorrhoids who were assigned to US surgery in a
      previous randomized trial. RESULTS: The pain scores were significantly lower in
      the THD patients on days 6 and 7 after the operation. The number of analgesic
      tablets consumed during the first postoperative week in the THD patients was
      significantly lower than that in the US patients. The blood loss was
      significantly greater in the THD patients. The hospital stay and length of time
      until the first defecation after surgery were both significantly shorter in the
      THD patients. The postoperative complications were comparable between the two
      groups of patients. CONCLUSION: The THD surgery was as effective as the US
      surgery for the treatment of hemorrhoids in the short term. THD surgery might be
      a preferred treatment because it is associated with a similar complication rate
      and short-term results, but results in lower postoperative pain and analgesic
      requirements compared with the US surgery.

PMID- 24682585
TI  - Prenatal diagnosis and management of an intestinal volvulus with meconium ileus
      and peritonitis.
AB  - Fetal intestinal volvulus is a rare but serious finding with a high risk of
      potential life threatening fetal complications. Delay in diagnosis or treatment
      can increase mortality and morbidity. We report a case of mild fetal bowel
      dilatation at 30 weeks of gestation and intestinal volvulus presented by the
      'whirl-sign', intestinal perforation and meconium peritonitis with fetal ascites
      and polyhydramnios at 33 weeks of gestation. This case emphasizes the role of
      examination of the bowel in third trimester ultrasound and the importance of
      quick decision to delivery and interdisciplinary perinatal management at
      suspected fetal volvulus with bowel necrosis and intraabdominal bleeding. 

PMID- 24682586
TI  - Clinical features of macrophage activation syndrome in the adult northern Chinese
      population.
AB  - OBJECTIVE: Macrophage activation syndrome (MAS) is a relatively rare but
      potentially fatal complication of childhood rheumatic illnesses. We sought to
      provide insight for the timely recognition and diagnosis of MAS and efficacious
      disease management in adults with rheumatic diseases. METHODS: Clinical files for
      eight adult MAS patients treated at the Second Affiliated Hospital of Harbin
      Medical University were analyzed for clinical manifestations, laboratory
      investigations, therapeutic measurements and clinical outcomes. RESULTS: The
      study included male and female patients with ages ranging from 16 to 59 years
      old. All patients were diagnosed with underlying rheumatic diseases with five
      patients having adult-onset Still's disease (AOSD), two patients having systemic
      lupus erythematosus (SLE) and one patient having Sjogren's syndrome (SS). The
      interval from fever onset to MAS diagnosis varied from seven days to 40 days. The
      most common clinical presentations were prolonged high fever, respiratory
      symptoms and jaundice. No patients had symptoms involving the central nervous
      system (CNS). Laboratory findings showed peripheral cytopenias, elevated liver
      enzymes, elevated triglycerides, hypofibrinogenemia and bone marrow
      hemophagocytosis. Potential effective treatments for MAS include glucocorticoid
      plus immunoglobulin therapy, but delays in diagnosis and treatment may lead to a
      fatal disease course. CONCLUSION: MAS in adults may not be as rare as was once
      thought, although the clinical features of MAS in adults often differ from those
      seen in children. The MAS mortality in adults is far higher than that for
      children. A diagnosis of MAS should be considered when a patient with rheumatic
      disease presents with prolonged high fever, peripheral cytopenia and liver
      failure. Collection of bone marrow aspirates is critical for accurate diagnosis
      and MAS therapy should begin as early as possible.

PMID- 24682587
TI  - A new spiral microelectrode assembly for electroporation and impedance
      measurements of adherent cell monolayers.
AB  - In this study, a new microelectrode assembly based on spiral geometry applicable
      to in situ electroporation of adherent cell monolayers on standard multiwell
      plates is presented. Furthermore, the structure is specially conceived to perform
      electrical impedance spectroscopy (EIS) measurements during electroporation. Its
      performance for cell membrane permeabilization is tested with a fluorescent
      probe. Gene electrotransfer is also assayed using a plasmid DNA encoding GFP in
      four different cell lines (CHO, HEK293, 3T3-L1 and FTO2B). Additionally, siRNA
      alpha-GFP electrotransfection is tested in GFP gene-expressing CHO cells. Our
      data show considerable differences between permeabilization and gene transfer
      results and cell line dependence on gene expression rates. Successful siRNA
      electro-mediated delivery is also achieved. We demonstrate the applicability of
      our device for electroporation-mediated gene transfer of adherent cells in
      standard laboratory conditions. Finally, electrical impedance measurements during
      electroporation of CHO and 3T3-L1 cells are also given. 

PMID- 24682588
TI  - Cutaneous scalp metastasis as the first indication of a clinically silent
      retroperitoneal leiomyosarcoma and of its further relapse as metastatic
      widespread disease.

PMID- 24682589
TI  - Still going strong: Leeuwenhoek at eighty.
AB  - At age 80, Antony van Leeuwenhoek was a world-famous scientist who came from a
      prosperous Delft family with a heritage of public service. He continued that
      tradition by serving in paid municipal offices. Self-taught, he began his
      scientific career in his 40s, when he began making hundreds of tiny single-lens
      microscopes. Pioneering the use of now-common microscopic techniques, he was the
      first human to see microbes and microscopic structures in animals, plants, and
      minerals. Over 50 years, he wrote only letters, more than 300 of them, and
      published half of them himself. More than a hundred were published in translation
      in the Royal Society's Philosophical Transactions. Today, Leeuwenhoek is
      considered in the lesser rank of scientists and is not well known outside of his
      homeland. Recent archival research in Delft has contributed new information about
      his life that helps to contextualize his science, but much remains to be learned.

PMID- 24682590
TI  - Efficacy of serial excisions of melanocytic nevi on the face using a carbon
      dioxide laser: a cosmetic point of view.
AB  - In cosmetic clinical practice, many patients express the desire for removal of
      melanocytic nevi, especially those on the face. The carbon dioxide (CO2) laser
      currently is the preferred for treatment of such lesions because of less scar
      formation, less bleeding, and simplicity of the procedure. However, if the
      diameter of the lesion is greater than 5 mm, many clinicians prefer surgical
      resection to laser resection because laser resection of relatively large nevi
      often results in the formation of a conspicuous dimple. The authors developed a
      serial laser excision method for melanocytic nevi larger than 5 mm, with division
      of the lesion into multiple segments, which allowed the ablated area to gain
      optimal granulation and reepithelialization, leading to a satisfactory cosmetic
      appearance. This novel procedure was performed for 25 patients with melanocytic
      nevi ranging from 5 to 10 mm in diameter. The lesions were divided into two
      segments in 21 patients, three segments in 3 patients, and four segments in 1
      patient. The divided parts of the lesions were ablated by CO2 laser serially at
      intervals of 2-4 weeks. All the patients obtained optimal granulation and
      epithelialization in the treated lesions, and the final appearance was
      satisfactory. Although the therapeutic period was longer than for a surgical
      excision or a single laser treatment, the new treatment approach of serial
      excision by CO2 laser achieved favorable outcomes for the treatment of relatively
      large nevi 5-10 mm in size. LEVEL OF EVIDENCE V: This journal requires that
      authors assign a level of evidence to each article. For a full description of
      these Evidence-Based Medicine ratings, please refer to the Table of Contents or
      the online Instructions to Authors www.springer.com/00266 .

PMID- 24682591
TI  - Preoperative chemotherapy in gastric cancer: expanding the indications, limiting
      the overuse.

PMID- 24682592
TI  - Low 25-hydroxyvitamin D levels in people with a solid tumor cancer diagnosis: the
      tip of the iceberg?
AB  - PURPOSE: Low serum 25-hydroxyvitamin D [25(OH)D] levels have been linked to both
      cancer incidence and poor prognosis. The frequency of 25(OH)D tests and clinical
      factors associated with low levels in cancer patients are unknown. PATIENTS AND
      METHODS: Electronic medical records from 2006 to 2007 of 39,252 adult solid tumor
      patients were reviewed. Data included demographics, cancer sites (primary and
      metastatic), and first serum 25(OH)D level during the study period. Laboratory
      data, comorbidities, selected medications, and anticancer treatment within the
      prior 2 months were recorded. Data were compared between (1) those tested and not
      tested and (2) 25(OH)D levels<=10 ng/ml (deficient), 11-30 ng/ml (insufficient),
      and >=31 ng/ml (sufficient). Stepwise logistic regression identified independent
      predictors of low serum 25(OH)D levels. RESULTS: The cohort was 86% Caucasian and
      48% female with a mean age of 63+/-14 years (mean+/-SD). The most prevalent
      cancer was breast (19%). In total, 2,098 (5%) had a 25(OH)D test. Of those
      tested, 133 (6%) had levels<=10 ng/ml and 1,311 (62%) 11-30 ng/ml. Tests were
      more frequent in females and in those with breast, skin, and thyroid cancers
      (P<0.001). Low 25(OH)D levels were associated (in univariable analyses) with male
      gender, non-Caucasian race, gastrointestinal tumor primary sites, metastatic
      disease, benign liver disease, low serum albumin, and elevated liver enzymes.
      Significant factors in multivariable models for 25(OH)D levels<=10 and <=30 ng/ml
      included non-Caucasian race, primary cancer site, and test calendar month.
      Vitamin D supplements and recent antineoplastic medication were associated with
      sufficient levels. CONCLUSIONS: Low (deficient or insufficient) 25(OH)D serum
      levels were highly prevalent in people with solid tumors. Vitamin D tests were
      infrequent and paradoxically less often done in high-risk groups. Tests were more
      frequent in females and in those with breast, skin, and thyroid cancers. Further
      research should examine role of routine 25(OH)D tests, the clinical consequences
      of low levels, and therapeutic supplementation in people with cancer.

PMID- 24682593
TI  - Registration of aggressive incidents in an adolescent forensic psychiatric unit
      and implications for further practice.
AB  - Although aggression is part of daily life in psychiatric units for adolescents,
      empirical data on its prevalence are sparse. Only few studies have described
      prevalence of aggressive incidents in adolescent psychiatric wards, and data in
      forensic psychiatric care are even more limited. Available studies reported high
      prevalence rates of aggression, ranging from 0.4 to 2.4 incidents of aggression
      per day across (forensic) child and adolescent psychiatric units. Between 27 and
      78 % of all admitted youth committed an aggressive act. In this study, we
      collected systematically registered data of all aggressive incidents from the
      first 2 years (2010-2012) on a newly established forensic adolescent psychiatric
      unit, which used a formal aggression management program embedded in the social
      competence model, which is based on early intervention in the 'chain of behavior'
      to prevent any further escalation. The inclusion of also minor aggressive
      incidents is unique in the literature and the clinical relevance is highlighted.
      A mean of one incident a day took place, with each adolescent involved in at
      least one incident. Notably, 1.7 aggressive incidents per month made seclusion of
      restraint use necessary. Based on the social competence theory, the aggression
      management model suggests intervening early in the cascade of aggression, in
      order to prevent further escalation and reduce the need for intrusive
      interventions. Evidence supported that aggression is a contextual event, as
      external factors clearly influence the incidence of aggression. Aggression
      management should be built on both relational and structural security.

PMID- 24682594
TI  - Sexual quality of life after total phalloplasty in men with penile deficiency: an
      exploratory study.
AB  - PURPOSE: Total phalloplasty is rarely performed today in males with severe penile
      deficiency, despite its successful use in the transgender population. Can
      phalloplasty replicate the complexity of penile anatomy and function on the long
      term? METHODS: Sexual quality of life (QoL) was assessed in 10 men (aged 20-43
      years) at least 1 year after phalloplasty in a single institution (80 % radial
      forearm flap and 20 % anterolateral thigh flap). In all but one, an erectile
      prosthesis was implanted on average 1 year after phallic reconstruction. Sexual
      QoL outcomes were compared to those of men with hypospadias repair (n = 73) and
      control men (n = 50). RESULTS: After phalloplasty (mean 36.9 months, 14-92
      months), all men were sexually active (80 % intercourse and 100 % masturbation
      with orgasm and ejaculation). However, 75 % indicated to be inhibited in seeking
      sexual contacts, compared to 40 % of hypospadias patients (p < 0.05) and 11 % of
      controls (p < 0.01). Although 90 % were satisfied with the final surgical result,
      dissatisfaction with some aspects of genital appearance was present in 50 %.
      Erogenous neophallus sensitivity was said to be less than previously hoped for.
      Six men developed urinary complications (urethral stricture and/or fistula), and
      one man underwent revision of the erectile implant because of dysfunction.
      Nevertheless, all indicated they would choose again for phalloplasty if
      necessary. CONCLUSIONS: Total phalloplasty opens new horizons for the treatment
      of men with penile deficiency, but limitations of the technique should be
      emphasized prior to surgery. An exploration of patient expectations and continued
      follow-up including psychological support is important for optimizing
      psychosexual comfort.

PMID- 24682595
TI  - Prediction of refractive outcome after cataract surgery using partial coherence
      interferometry: comparison of SRK/T and Haigis formulae.
AB  - To compare the accuracy of the predictions of SRK/T and Haigis formulae,
      incorporating all the parameters calculated using Zeiss IOLMaster Scan, based on
      partial coherence interferometry, and to analyse the effect of updating or
      optimisation of the constants on the post-operative result. A retrospective study
      was done on 51 consecutive patients, who underwent phacoemulsification by a
      single surgeon with a temporal corneal incision and a standard Alcon Acrysof MA30
      implant in the bag. The pre-operative data were measured using Zeiss IOLMaster
      scan, and the IOL power calculations were done using both SRK/T and Haigis
      formulae. The final implant power selection was based on SRK/T predictions. The
      patients were divided into three groups depending on the axial length, and the
      post-operative results were analysed at 4 weeks. The difference between the
      predicted value and the post-operative spherical equivalent was calculated for
      both the formulae, and a paired t test used for significance. The axial length
      ranged from 20.93 to 25.16 mm. The error for Haigis was less compared to SRK/T
      overall and SRK/T resulted in an average hypermetropia 0.69 D and Haigis resulted
      in an average myopia of 0.16 D. The comparison between SRK/T and Haigis and the
      updated version of both using the paired t test shows a statistically significant
      difference, the p values being <0.03 and <0.01, respectively. The updated Haigis
      Formula with the optimised constants was significantly more accurate than SRK/T
      formula.

PMID- 24682596
TI  - Adenocarcinoma of Moll's gland with multiple metastases.

PMID- 24682597
TI  - Is insulin-like growth factor binding protein 2 associated with metastasis in
      lung cancer?
AB  - Insulin-like growth factor binding protein 2 (IGFBP2) is involved in the
      progression of many epithelial cancers. However, its role in non-small cell lung
      cancer (NSCLC), another type of epithelial cancer, remains unclear. We detected
      IGFBP2 expression using immunohistochemistry in surgically resected tumors from
      110 NSCLC patients, 37 of which had metastases. The positive rate of IGFBP2
      expression was compared between the metastatic and the non-metastatic group, and
      correlations of IGFBP2 expression with metastasis and overall survival were
      analyzed. We also investigated the expression of IGFBP2 in microvesicles (MVs)
      collected from primary lung cancer cell cultures, and in different locations of
      newly resected NSCLC tumors, using immunoblotting. The overall positive rate of
      IGFBP2 expression in lung cancer was 51.8 % and it was significantly higher in
      the metastatic group than in the non-metastatic group (70.3 and 42.5 %
      respectively, p < 0.01). And the higher the lymph node stage, the higher the
      positive rate. Cytoplasmic expression was predominant in the majority of the
      tumors. Based on multivariate regression analysis, IGFBP2 was correlated with
      metastasis and poor overall survival (Hazard ratio: 3.56 and 3.23 respectively).
      IGFBP2 was detectable in the MVs collected from IGFBP2 positive cell lines, and
      its expression was most abundant in the marginal region of the newly resected
      tumors. IGFBP2 is associated with metastasis and poor survival of lung cancer.
      Its presence in MVs and high abundance in the marginal region of tumors suggest
      that its association with metastasis may be related to tumor microenviroment
      remodeling in NSCLC.

PMID- 24682599
TI  - The change in intraocular pressure after pupillary dilation in eyes with
      pseudoexfoliation glaucoma, primary open angle glaucoma, and eyes of normal
      subjects.
AB  - To evaluate the change in intraocular pressure (IOP) after pharmacologic dilation
      in eyes with primary open angle glaucoma (POAG), pseudoexfoliation glaucoma
      (PXG), and eyes of normal subjects. This cross-sectional study was conducted in a
      university hospital-based setting. Patients with PXG, POAG, and normal subjects
      were consecutively selected and included in the study. Of the 125 eyes of 125
      subjects; 46 (25 female) had PXG, 42 (29 female) had POAG, and 37 (20 female)
      belonged to the control group. Pharmacologic dilation procedure consisted of
      instillation of topical phenylephrine HCL 10 % followed 5 min by tropicamide 1 %.
      Studied variables were pre- and post-dilation IOP and also baseline measurements
      of anterior chamber angle, central corneal thickness, and pupillary diameter by
      Pentacam HR (Oculus, Wetzlar, Germany). Clinically significant IOP change was
      defined as a change of >=2 mmHg from baseline. Randomly selected single eye of
      each patient was included in the analysis. The mean pre:post-dilation IOP of eyes
      with PXG and POAG was 17.39 +/- 3.89:17.54 +/- 3.98 and 15.92 +/- 2.37:16.07 +/-
      2.89 mmHg, respectively. The difference between the pre- and post-dilation IOP of
      eyes with PXG and POAG was not statistically significant. The eyes of control
      subjects, however, had a statistically significant reduction of IOP from 14.24 +/
      2.88 to 13.54 +/- 2.94 mmHg (P = 0.005). 28.3 % (13/46) of eyes with PXG, 16.7 %
      (7/42) of eyes with POAG, and 2.7 % (1/37) of control eyes showed a clinically
      significant IOP elevation from baseline after the dilation. In this study,
      glaucoma patients proportionally experienced a higher rate of clinically
      significant IOP elevation after pupillary dilation, when compared to normal
      subjects. 

PMID- 24682598
TI  - Membrane recruitment of endogenous LRRK2 precedes its potent regulation of
      autophagy.
AB  - Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of
      familial and idiopathic Parkinson's disease. However, the mechanisms for
      activating its physiological function are not known, hindering identification of
      the biological role of endogenous LRRK2. The recent discovery that LRRK2 is
      highly expressed in cells of the innate immune system and genetic association is
      a risk factor for autoimmune disorders implies an important role for LRRK2 in
      pathology outside of the central nervous system. Thus, an examination of
      endogenous LRRK2 in immune cells could provide insight into the protein's
      function. Here, we establish that stimulation of specific Toll-like receptors
      results in a complex biochemical activation of endogenous LRRK2, with early
      phosphorylation of LRRK2 preceding its dimerization and membrane translocation.
      Membrane-associated LRRK2 co-localized to autophagosome membranes following
      either TLR4 stimulation or mTOR inhibition with rapamycin. Silencing of
      endogenous LRRK2 expression resulted in deficits in the induction of autophagy
      and clearance of a well-described macroautophagy substrate, demonstrating the
      critical role of endogenous LRRK2 in regulating autophagy. Inhibition of LRRK2
      kinase activity also reduced autophagic degradation and suggested the importance
      of the kinase domain in the regulation of autophagy. Our results demonstrate a
      well-orchestrated series of biochemical events involved in the activation of
      LRRK2 important to its physiological function. With similarities observed across
      multiple cell types and stimuli, these findings are likely relevant in all cell
      types that natively express endogenous LRRK2, and provide insights into LRRK2
      function and its role in human disease. 

PMID- 24682600
TI  - In vitro susceptibility of Candida isolates from organ transplant recipients to
      newer antifungals.
AB  - Organ transplant recipients (OTR) are at higher risk of developing life
      threatening infections. In this study, we tested 527 Candida isolates obtained
      from the oral and genital mucosa from OTR and healthy controls in order to
      monitor antifungal susceptibility patterns in this particular risk group. Testing
      was carried out in parallel for already marketed azoles and anidulafungin.
      Minimal inhibitory concentrations (MICs) were determined using the E-test((r))
      for azoles and CLSI broth microdilution for anidulafungin. Overall, there was no
      difference in the distribution of Candida spp. for both groups, C. albicans being
      the most frequently isolated Candida sp. followed by C. glabrata. Also, there
      were only minor differences in the susceptibility patterns to all antifungal
      agents. All C. albicans isolates were fully susceptible to fluconazole and
      voriconazole. In C. glabrata, 2.2% (n = 1) were resistant to fluconazole, and
      82.6% (n = 38) to itraconazole, and in C. krusei, 66.7% (n = 2) were resistant in
      itraconazole. All strains were susceptible to voriconazole. Only fluconazole
      showed a higher rate of resistant C. glabrata isolates for OTR (3.7%), whereas
      the control group showed only intermediate susceptible and no resistant isolates.
      As there are no breakpoints established for posaconazole by CLSI, breakpoints
      determined by EUCAST were used. A total of 87.9% of C. albicans, 81.3% of C.
      parapsilosis and 66.7% of C. tropicalis were considered susceptible. C. glabrata
      and C. krusei showed higher MIC values and thus lesser susceptibility than the
      other Candida species. There were no differences observed between OTR and control
      groups. For anidulafungin, 99.8% of C. albicans isolates were susceptible, 0.2%
      were intermediate, whereas for C. glabrata, only 95.3% were susceptible, 0.2%
      were resistant and 4.5% were interpreted as intermediate. Interestingly, the two
      resistant isolates were found in the control group. Also, the controls showed a
      marginally higher percentage of intermediate strains compared to the transplant
      patients. All in all, resistant isolates were only observed for C. glabrata of
      the control group.

PMID- 24682601
TI  - Pazopanib: an alternative in taxane-resistant cutaneous angiosarcoma.

PMID- 24682602
TI  - Topical anesthetic preparations for rigid and flexible endoscopy: a meta
      analysis.
AB  - Transnasal endoscopy can cause pain or discomfort for the patient. Topical
      anesthetic has been used in an attempt to reduce this. However, there is no
      consensus on whether topical anesthetic is effective in optimizing patient
      experience during the procedure. The goal of this study was to perform a
      systematic review with meta-analysis of the efficacy of topical anesthetic on
      pain and comfort outcomes during endoscopy. Two authors independently searched
      the databases from inception to September 2013. Studies comparing topical
      anesthetic with placebo where the outcomes of interest were pain, comfort, or
      side effect outcomes were included. Sufficient data for meta-analysis were
      retrieved for ten trials with a total of 837 patients. The evidence suggests that
      local anesthetic alone or in combination with a vasoconstrictor is beneficial to
      patients' pain [standardized mean difference (SMD) = -0.21; p = 0.045] and
      comfort (SMD = -0.51; p < 0.001) outcomes when performing transnasal endoscopy.
      However, the topical anesthetic caused unpleasant sensation with respect to an
      unpleasant taste (SMD = 0.77; p < 0.001). In addition, there was no significant
      difference between a topical anesthetic spray and cotton type in pain and
      discomfort values. Applying topical anesthetic during transnasal endoscopy could
      reduce pain and discomfort. The spray and cotton type methods of topical
      anesthetic preparation showed no significant difference in terms of pain and
      discomfort during the procedure. However, further trials with good research
      methodology should be conducted to confirm our results.

PMID- 24682603
TI  - Geo-spatial analysis of the temporal trends of kharif crop phenology metrics over
      India and its relationships with rainfall parameters.
AB  - The Global Inventory Modeling and Mapping Studies bimonthly Normalized Difference
      Vegetation Index (NDVI) data of 8 * 8 km spatial resolution for the period of
      1982-2006 were analyzed to detect the trends of crop phenology metrics (start of
      the growing season (SGS), seasonal NDVI amplitude (AMP), seasonally integrated
      NDVI (SiNDVI)) during kharif season (June to October) and their relationships
      with the amount of rainfall and the number of rainy days over Indian
      subcontinent. Direction and magnitude of trends were analyzed at pixel level
      using the Mann-Kendall test and further assessed at meteorological subdivision
      level using field significance test (alpha = 0.1). Significant pre-occurrence of
      the SGS was observed over northern (Punjab, Haryana) and central (Marathwada,
      Vidarbha and Madhya Maharashtra) parts, whereas delay was found over southern
      (Rayalaseema, Coastal Andhra Pradesh) and eastern (Bihar, Gangetic West Bengal
      and Sub-Himalayan West Bengal) parts of India. North, west, and central India
      showed significant increasing trends of SiNDVI, corroborating the kharif food
      grain production performance during the time frame. Significant temporal
      correlation (alpha = 0.1) between the rainfall/number of rainy days and crop
      phenology metrics was observed over the rainfed region of India. About 35-40 % of
      the study area showed significant correlation between the SGS and the
      rainfall/number of rainy days during June to August. June month rainfall/number
      of rainy days was found to be the most sensitive to the SGS. The amount of
      rainfall and the number of rainy days during monsoon were found to have
      significant influence over the SiNDVI in 24-30 % of the study area. The crop
      phenology metrics had significant correlation with the number of rainy days over
      the larger areas than that of the rainfall amount. 

PMID- 24682604
TI  - Features and prognostic impact of distant metastasis in patients with stage IV
      lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis.
AB  - Mutated epidermal growth factor receptor (EGFR) and signaling pathways were
      associated with multiple brain and intra-pulmonary metastases, oncogenic
      progression and metastasis. However, features of metastasis to other organs and
      the independent prognostic influence of metastatic lesions were not elucidated in
      patients with lung cancer harboring EGFR mutations. Between January 2007 and
      April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma.
      Studied were 246 patients with available tumor EGFR mutation data who also
      underwent radiographic evaluation of lung, abdominal, brain, and bone metastases.
      The EGFR mutated group (N = 98) had significantly more metastatic lesions in the
      brain and bone than the wild-type group (N = 148): brain, 3 (1-93) versus 2 (1
      32) median (range), P = 0.023; bone, 3 (1-43) versus 2 (1-27), P = 0.035,
      respectively. In addition, EGFR mutations were significantly more frequent in
      patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P =
      0.004). Multivariate analysis showed that bone metastasis was a significant
      independent negative predictive factor of overall survival (OS) in patients with
      mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17-3.64; P =
      0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37-3.20; P < 0.001). In conclusion,
      patients with mutated EGFR had more lung, brain, and bone metastases, and bone
      metastasis was an independent negative predictor of OS.

PMID- 24682605
TI  - Longitudinal association of county-level economic indicators and child
      maltreatment incidents.
AB  - To evaluate the association between economic indicators (unemployment and
      mortgage foreclosure rates) and volume of investigated and substantiated cases of
      child maltreatment at the county level from 1990 to 2010 in the Commonwealth of
      Pennsylvania. County-level investigated reports of child maltreatment and
      proportion of investigated cases substantiated by child protective services in
      the Commonwealth of Pennsylvania were compared with county-level unemployment
      rates from 1990 to 2010, and with county-level mortgage foreclosure rates from
      2000 to 2010. We employed fixed-effects Poisson regression modeling to estimate
      the association between volume of investigated and substantiated cases of
      maltreatment, and current and prior levels of local economic indicators adjusting
      for temporal trend. Across Pennsylvania, annual rate of investigated maltreatment
      reports decreased through the 1990s and rose in the early 2000s before reaching a
      peak of 9.21 investigated reports per 1,000 children in 2008, during the recent
      economic recessionary period. The proportion of investigated cases substantiated,
      however, decreased statewide from 33 % in 1991 to 15 % in 2010. Within counties,
      current unemployment rate, and current and prior-year foreclosure rates were
      positively associated with volume of both investigated and substantiated child
      maltreatment incidents (p < 0.05). Despite recent increases in investigations,
      the proportion of investigated cases substantiated decreased by more than half
      from 1990 to 2010 in Pennsylvania. This trend suggests significant changes in
      substantiation standards and practices during the period of study. Economic
      indicators demonstrated strong association with investigated and substantiated
      maltreatment, underscoring the urgent need for directing important prophylactic
      efforts and resources to communities experiencing economic hardship.

PMID- 24682606
TI  - Efficacy of surgery for rotator cuff tendinopathy: a systematic review.
AB  - The objective of this study is to review randomized controlled trials evaluating
      the efficacy of surgery for the treatment of rotator cuff (RC) tendinopathy.
      Studies up to August 2013 were located in the PubMed, Embase, CINAHL, and PEDro
      databases using relevant keywords. Studies were included if: (1) participants had
      rotator cuff tendinopathy, (2) the trials were conducted on an adult population
      (>=18 years old), (3) at least one of the interventions studied was a surgical
      procedure, (4) study design was a randomized controlled trial (RCT), and (5) the
      article was written in English or French. Characteristics of the included studies
      were extracted using a standardized form. Two independent raters reviewed the
      methodological quality of the studies using the Risk of Bias Assessment tool
      developed by the Cochrane Collaboration Group. Differences were resolved by
      consensus. Fifteen trials met our inclusion criteria. After consensus, the mean
      methodological quality for all studies was 58.9 +/- 10.8 %. In three out of four
      RCTs of moderate or low methodological quality, no significant difference in
      treatment effectiveness was observed between open or arthroscopic acromioplasty
      compared to exercises in the treatment of RC tendinopathy. Based on two studies
      of low or moderate methodological quality, no difference in treatment
      effectiveness was observed between arthroscopic and open acromioplasty. Two other
      RCTs of low to moderate quality, however, found that arthroscopic acromioplasty
      yielded better results in the short-term for shoulder range of motion in flexion
      but that both procedures were comparable in the long-term. One additional study
      favored open acromioplasty over arthroscopic acromioplasty for the treatment of
      RC tendinopathy. Based on low- to moderate-quality evidence, acromioplasty, be it
      open or arthroscopic, is no more effective than exercises for the treatment of RC
      tendinopathy. Low-grade evidence also suggests that arthroscopic acromioplasty
      may yield better results in the short-term for shoulder range of motion in
      flexion compared to open acromioplasty, but long-term results are comparable
      between the two types of surgery. More high-quality RCTs are required in order to
      provide comprehensive treatment guidelines to healthcare providers.

PMID- 24682607
TI  - Cloning and expression of three ladA-type alkane monooxygenase genes from an
      extremely thermophilic alkane-degrading bacterium Geobacillus thermoleovorans
      B23.
AB  - An extremely thermophilic bacterium, Geobacillus thermoleovorans B23, is capable
      of degrading a broad range of alkanes (with carbon chain lengths ranging between
      C11 and C32) at 70  degrees C. Whole-genome sequence analysis revealed that
      unlike most alkane-degrading bacteria, strain B23 does not possess an alkB-type
      alkane monooxygenase gene. Instead, it possesses a cluster of three ladA-type
      genes, ladAalphaB23, ladAbetaB23, and ladB B23, on its chromosome, whose protein
      products share significant amino acid sequence identities, 49.8, 34.4, and 22.7
      %, respectively, with that of ladA alkane monooxygenase gene found on a plasmid
      of Geobacillus thermodetrificans NG 80-2. Each of the three genes, ladAalphaB23,
      ladAbetaB23, and ladB B23, was heterologously expressed individually in an alkB1
      deletion mutant strain, Pseudomonas fluorescens KOB2Delta1. It was found that all
      three genes were functional in P. fluorescens KOB2Delta1, and partially restored
      alkane degradation activity. In this study, we suggest that G. thermoleovorans
      B23 utilizes multiple LadA-type alkane monooxygenases for the degradation of a
      broad range of alkanes.

PMID- 24682608
TI  - Life in extreme environments: microbial diversity in Great Salt Lake, Utah.
AB  - Great Salt Lake (GSL) represents one of the world's most hypersaline
      environments. In this study, the archaeal and bacterial communities at the North
      and South arms of the lake were surveyed by cloning and sequencing the 16S rRNA
      gene. The sampling locations were chosen for high salt concentration and the
      presence of unique environmental gradients, such as petroleum seeps and high
      sulfur content. Molecular techniques have not been systematically applied to this
      extreme environment, and thus the composition and the genetic diversity of
      microbial communities at GSL remain mostly unknown. This study led to the
      identification of 58 archaeal and 42 bacterial operational taxonomic units. Our
      phylogenetic and statistical analyses displayed a high biodiversity of the
      microbial communities in this environment. In this survey, we also showed that
      the majority of the 16S rRNA gene sequences within the clone library were
      distantly related to previously described environmental halophilic archaeal and
      bacterial taxa and represent novel phylotypes. 

PMID- 24682609
TI  - Paralimbic gray matter reductions in incarcerated adolescent females with
      psychopathic traits.
AB  - Psychopathy-related paralimbic and limbic structural brain abnormalities have
      been implicated in incarcerated adult and adolescent male samples. However, there
      have been few neuroimaging studies of psychopathic traits in females in general
      and no studies from incarcerated female youth in particular. Here we present the
      first study to examine the relationship between brain gray matter volumes and
      psychopathic traits (assessed using the Psychopathy Checklist-Youth Version [PCL
      YV]) in a sample of maximum-security incarcerated female adolescents (N = 39;
      mean age = 17.6 years). Consistent with male samples, regional gray matter
      volumes were negatively related to psychopathic traits in female youth offenders
      in limbic and paralimbic areas, including orbitofrontal cortex, parahippocampal
      cortex, temporal poles, and left hippocampus. These results provide evidence that
      psychopathic traits manifest similar neural abnormalities across sex and age. 

PMID- 24682610
TI  - Transoral laser microsurgery for early and moderately advanced laryngeal cancers:
      outcomes from a single centralised United Kingdom centre.
AB  - Transoral laser microsurgery (TLM) represents an important treatment for selected
      laryngeal cancers. Utilisation of TLM, however, is highly variable between United
      Kingdom (UK) centres, and published data relating to its use in the UK is scarce.
      We report outcomes from our tertiary referral centre, and highlight lessons
      learned. Patients undergoing primary TLM for laryngeal cancer with curative
      intent (2007-2011) were studied retrospectively. Survival analyses were evaluated
      using the Kaplan-Meier method and log-rank statistics used to examine the
      influence of several variables. Overall, 170 cases were included-153 glottic and
      17 supraglottic. Median follow-up was 39 months (range 14-79 months). Respective
      3-year local control (LC), overall survival (OS), disease-specific survival
      (DSS), and disease-free survival were 92, 92, 98, and 86 % for glottic
      carcinomas. Three-year LC and OS were both 88 % for supraglottic carcinomas. For
      glottic cases, a significant impact of pT stage on DSS was observed, and of age
      on OS. Median hospital stay was one and 19 days for glottic and supraglottic
      cases respectively, with respective 3-year laryngeal preservation rates of 97 and
      94 %, and tracheostomy rates of 0 and 29 %. One patient in the glottic group and
      four in the supraglottic group failed to regain swallowing function post
      operatively, remaining either PEG dependent or undergoing functional total
      laryngectomy. Our series confirms the oncological and functional efficacy of TLM,
      offering a unique large-scale UK perspective. Our experience indicates, however,
      that treatment of larger supraglottic tumours should be considered carefully, as
      functional outcomes may be compromised.

PMID- 24682611
TI  - Initial staging of head and neck squamous cell carcinoma. What is the place of
      bronchoscopy and upper GI endoscopy?
AB  - To determine the place of bronchoscopy and upper GI endoscopy in the initial
      staging of head and neck squamous cell carcinoma (HNSCC). A 10-year retrospective
      study was conducted on a series of 838 patients. As part of initial staging of
      the tumor, all patients were examined by neck and chest CT scan, 487 patients
      were examined by bronchoscopy and 588 patients were examined by upper GI
      endoscopy. Esophageal cancer was detected in 4.25 % of cases and lung cancer in
      6.35 % of cases. Chest CT scan was statistically superior to bronchoscopy to
      detect second lung cancers (p < 0.05). On multivariate analysis, oral cancers (p
      = 0.009) and multiple (synchronous) HNSCC (p = 0.009) were associated with the
      presence of a second lung cancer. Systematic bronchoscopy (performed by a
      pulmonologist) might not to be indicated for initial staging of HNSCC,
      particularly in the presence of normal chest CT scan. In case of abnormal Chest
      CT scan, patients should be referred to a pulmonologist. However, as oral cancers
      and multiple (synchronous) HNSCCs were statistically associated with the presence
      of a second lung cancer in this study, bronchoscopy might be indicated in these
      cases in order to detect rare small proximal bronchic lesions which might be
      invisible on chest CT scan in these patients at risk. More, systematic upper GI
      endoscopy (performed by a gastroenterologist) for initial staging of HNSCC might
      also not to be indicated in a majority of cases.

PMID- 24682612
TI  - Time to conception and time to live birth in women with unexplained recurrent
      miscarriage.
AB  - STUDY QUESTION: What is the time to conception in a cohort of women with
      unexplained recurrent miscarriage (RM). SUMMARY ANSWER: Median time to conception
      in women diagnosed with unexplained RM was 21 weeks (interquartile range (IQR) 8
      55 weeks), with a cumulative incidence of conception of 74% after 12 months of
      trying to conceive. WHAT IS KNOWN ALREADY: There is no effective treatment in
      couples with unexplained RM. Adequate counselling about their prognosis, for
      example time to conception and time to a live birth, is therefore very important.
      So far, there are no studies that give insight on these issues. STUDY DESIGN,
      SIZE, DURATION: A nested prospective cohort study was performed from February
      2004 through July 2009 within a multicentre randomized placebo-controlled trial
      (ALIFE trial) on anticoagulant treatment in 364 women with unexplained RM.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 251 women who were not
      pregnant at the time of diagnosis of unexplained RM were included in this study.
      Of these, 13% became pregnant with ART, and all other women conceived naturally.
      The primary outcome was time to conception in weeks, calculated from the moment
      of diagnosis until conception measured by a urinary HCG. Secondary outcome was
      time to a live birth in the subsequent pregnancy. The relative prognostic
      significance of female age, the number of preceding miscarriages, interventions
      within the trial and the presence or absence of a preceding late miscarriage, a
      previous live birth and factor V Leiden mutation, was evaluated by Cox regression
      for time to conception and by competing risk modelling for time to live birth,
      respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative incidence of
      conception was 56% after 6 months, 74% after 12 months and 86% after 24 months of
      which 65% resulted in a live birth. The median time to conception was 21 weeks
      (IQR 8-55 weeks). Of potential prognostic factors, the presence of the factor V
      Leiden mutation resulted in a significantly shorter median time to conception of
      11 weeks for carriers versus 23 weeks for non-carriers (hazard ratio (HR) 1.94,
      95% confidence interval (CI) 1.03-3.65). The cumulative incidence of a live birth
      of the subsequent pregnancy was 0% after 6 months, 23% after 12 months and 50%
      after 24 months. The median time to a live birth of the subsequent pregnancy was
      102 weeks (IQR 82-115 weeks). The number of previous miscarriages was the only
      prognostic factor (HR 0.83, 95% CI 0.74-0.94) significantly associated with time
      to a live birth of the subsequent pregnancy. LIMITATIONS, REASONS FOR CAUTION: In
      our study only the subsequent pregnancy after diagnosing unexplained RM was
      included. A future collection of cumulative follow-up data of all the women
      included in this cohort may provide outcomes of all pregnancies following the
      diagnosis of unexplained RM. WIDER IMPLICATIONS OF THE FINDINGS: Time to
      conception in women diagnosed with unexplained RM appears to be comparable with
      time to conception in healthy fertile women, as reported in the literature. The
      interesting finding that women with Factor V Leiden mutation have a significant
      shorter time to conception may suggest a favourable embryo implantation process.
      Future research is needed to confirm these findings and unravel the biology of
      early implantation. STUDY FUNDING/COMPETING INTEREST(S): The RCT used for this
      nested cohort study was funded by a grant (945-27-003) from the Netherlands
      Organization for Health Research and Development and a grant from
      GlaxoSmithKline. Study drugs (aspirin and placebo) were packaged and donated by
      Meda Pharma. This analysis was supported by a VIDI innovative research grant from
      the Netherlands Organisation for Scientific Research (NWO) 016.126.364. There are
      no potential conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This
      cohort study was nested in the randomized controlled trial; ALIFE study (Current
      Controlled Trials number, ISRCTN 58496168).

PMID- 24682613
TI  - Bleeding pattern and user satisfaction in second consecutive levonorgestrel
      releasing intrauterine system users: results of a prospective 5-year study.
AB  - STUDY QUESTION: What is the bleeding pattern during second consecutive
      levonorgestrel-releasing intrauterine system (LNG-IUS) use? SUMMARY ANSWER:
      Consecutive use of LNG-IUS is associated with a predictable bleeding pattern,
      characterized by the absence of the initial period of irregular bleeding seen
      after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast
      majority of women. WHAT IS KNOWN ALREADY: With increased popularity of the LNG
      IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB),
      consecutive use of the system is becoming more frequent. One previous study
      showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was
      small. STUDY DESIGN, SIZE, DURATION: A prospective multicenter study in four
      European countries recruited women who wished to continue with LNG-IUS use
      immediately after the first 5-year period. A total of 204 women were followed up
      until the end of the first year of the second IUS. Thereafter 170 women continued
      into the extension phase of the study up to the full 5 years of use of the second
      IUS and 144 women continued to the end of the study. PARTICIPANTS, SETTING,
      METHODS: A total of 170 women (mean age 39 years) who had been using their first
      LNG-IUS for between 4 years 3 months and 4 years 9 months, either for
      contraception or for treatment of HMB, and who planned to replace the device with
      a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A
      total of 17 centers in four European countries were involved in the study.
      Bleeding patterns were analyzed using daily bleeding diaries using 90-day
      reference periods (RP) for the first year of the second IUS use and for the last
      RP of each year during Years 2-5 of use. MAIN RESULTS AND THE ROLE OF CHANCE:
      Approximately 70% of women were free of bleeding during Years 2-5 and up to 49%
      were amenorrheic. There was a slight increase in the number of bleeding/spotting
      days of ~3 days during the first RP immediately after the placement of the second
      IUS, whereafter the number of bleeding/spotting days returned to the level
      preceding the second IUS insertion or below that. Absence of bleeding was
      associated with high overall satisfaction and continuation rates. No serious
      adverse events assessed as related to the LNG-IUS use occurred during the 5-year
      period. The cumulative expulsion rate during the 5-year study period was 1.2%.
      The sample size was large enough to study bleeding patterns, and subjects are
      likely to represent typical consecutive IUS users, and therefore, the role of
      chance is small. LIMITATIONS, REASONS FOR CAUTION: The women represent a selected
      group as they had already successfully used their first IUS for almost 5 years
      and were willing to continue its use-however, this is currently a common clinical
      situation. The results may therefore not be extrapolated to first-time users of
      the LNG-IUS. WIDER IMPLICATIONS OF THE FINDINGS: These data are of importance
      when counseling women who are making decisions concerning long-term
      contraception. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by
      Bayer Pharma AG. P.I. and T.S. are full-time employees of Bayer Pharma AG. O.H.
      and K. G-D. have received consultancy fees from Bayer Pharma AG. The publication
      was developed jointly by all authors without third-party involvement and no
      honoraria were paid for any authors for their contribution to this manuscript.
      TRIAL REGISTRATION NUMBER: NCT00393198.

PMID- 24682614
TI  - Antral follicle count as a marker of ovarian biological age to reflect the
      background risk of fetal aneuploidy.
AB  - STUDY QUESTION: Can antral follicle count (AFC) measured during pregnancy be used
      as a marker of ovarian age to assess the background risk of fetal aneuploidy?
      SUMMARY ANSWER: AFC was lower than expected according to maternal chronological
      age in trisomic pregnancies; therefore ovarian age could potentially reflect a
      more precise background risk of fetal aneuploidy screening. WHAT IS KNOWN
      ALREADY: The decline in a woman's reproductive function is determined by a
      decline in the ovarian follicle pool and the quality of oocytes. The quantitative
      status of ovarian reserve can be indirectly assessed by AFC, but the role of AFC
      as an aneuploidy risk marker in pregnant women has not been assessed yet. STUDY
      DESIGN, SIZE, DURATION: Our study comprised a prospective cohort including 1239
      singleton pregnancies scanned before 14 weeks in our center during a 14-month
      period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reference ranges for AFC were
      constructed using 812 spontaneously conceived, chromosomally normal singleton
      ongoing pregnancies using the Lambda-Mu-Sigma method. The study population (n =
      934) included 19 pregnancies with viable autosomal trisomies (trisomies 21, 18
      and 13), 17 non-viable autosomal trisomies (other than 21, 18 or 13), 7
      monosomies X, 1 sex trisomy and 3 triploidies (total n = 47 with chromosomal
      abnormalities). AFC in chromosomally abnormal pregnancies was plotted against the
      reference ranges. AFC multiple of the median was calculated according to the
      median AFC obtained by each year of age. MAIN RESULTS AND THE ROLE OF CHANCE:
      Sixty-eight percent of women carrying a pregnancy with viable trisomies and 65%
      with non-viable trisomies presented an AFC below the 50th percentile. The median
      ovarian age in viable trisomies and non-viable trisomies was estimated to be 3
      and 6 years above than median maternal age, respectively. However, the median
      ovarian age in monosomies X and triploidies was not higher than median maternal
      age. LIMITATIONS, REASONS FOR CAUTION: We did not assess the intra- and inter
      observer reliability, or use specific three-dimensional analysis which may have
      advantages over our two-dimensional study. In clinical practice, a drawback for
      assessing AFC during pregnancy is that transvaginal ultrasound is needed at the
      11- to 13-week scan, when the transabdominal approach is used most commonly.
      Furthermore identifying ovaries by ultrasound during pregnancy could be
      challenging. WIDER IMPLICATIONS OF THE FINDINGS: Considering that AFC reflects
      ovarian aging, this 'ovarian biological age' could potentially reflect a more
      precise background risk of fetal aneuploidy. STUDY FUNDING/COMPETING INTEREST(S):
      This study was supported by PI 11/00685. Instituto de Salud Carlos III. Fondo de
      Investigacion Sanitaria. No competing interests declared.

PMID- 24682615
TI  - Habitat and occurrence of ixodid ticks in the Liguria region, northwest Italy.
AB  - Questing ticks were collected during monthly dragging sessions (March-August
      2011) in three provinces of the Liguria region, north-western Italy, to evaluate
      the species occurrence, spatial distribution and relative abundance. A total of
      1,464 specimens were collected in 94 dragging sites. Ixodes ricinus was the most
      abundant species (81.3 % of collected ticks), followed by Haemaphysalis punctata
      (10.9 %), Dermacentor marginatus (5.5 %), Ixodes frontalis (1.3 %), and
      Rhipicephalus spp. (0.9 %). Ixodes frontalis is reported for the first time in
      Liguria. An aggregation of I. ricinus positive sites was observed in inland areas
      characterized by dense forests dominated by deciduous trees (Castanetum and
      Fagetum phytoclimatic zones), especially in the west of the region where the
      differences in the Normalized Difference Vegetation Index (NDVI) were higher
      between inland and coastal sites. Random-effect logistic regression was used to
      model the associations of NDVI and season with the probability of finding host
      seeking I. ricinus nymphs [corrected]. The NDVI was a good predictor of I.
      ricinus nymphs abundance, and confirmed its utility in discriminating habitat
      suitability for this vector in north-western coastal Italy, where dry habitat
      conditions may limit the distribution of this species.

PMID- 24682616
TI  - Rapid cold hardening response in the predatory mite Neoseiulus californicus.
AB  - We investigated the rapid cold hardening (RCH) response in the predatory mite
      Neoseiulus californicus (McGregor) (Acari: Phytoseiidae). On direct exposure, <=2
      % of adult females survived -10  degrees C for 2 h. However, when acclimatized
      first at 5  degrees C for 1 h, 75 % of females survived. RCH could also be
      induced by acclimatization at 30  degrees C for 2 h or anoxia (oxygen-free
      nitrogen) for 1-2 h. All immature stages showed enhanced survival when
      acclimatized at 5  degrees C for 2 h before exposure to -10  degrees C.
      Acclimatization at 30  degrees C induced RCH only in eggs and deutonymphs, and
      anoxia was effective for eggs, larvae, and deutonymphs. The variability among
      immature stages may be attributed to the cost associated with the acclimatization
      treatments. Our findings suggest that RCH may promote the survival of N.
      californicus during unexpected changes in temperatures, and can be an important
      feature particularly when this natural enemy is introduced to non-native
      environments.

PMID- 24682617
TI  - Ozone affects ascorbate and glutathione biosynthesis as well as amino acid
      contents in three Euramerican poplar genotypes.
AB  - Ozone is an air pollutant that causes oxidative stress by generation of reactive
      oxygen species (ROS) within the leaf. The capacity to detoxify ROS and repair ROS
      induced damage may contribute to ozone tolerance. Ascorbate and glutathione are
      known to be key players in detoxification. Ozone effects on their biosynthesis
      and on amino acid metabolism were investigated in three Euramerican poplar
      genotypes (Populus deltoides Bartr. * Populus nigra L.) differing in ozone
      sensitivity. Total ascorbate and glutathione contents were increased in response
      to ozone in all genotypes, with the most resistant genotype (Carpaccio) showing
      an increase of up to 70%. Reduced ascorbate (ASA) concentration at least doubled
      in the two most resistant genotypes (Carpaccio and Cima), whereas the most
      sensitive genotype (Robusta) seemed unable to regenerate ASA from oxidized
      ascorbate (DHA), leading to an increase of 80% of the oxidized form. Increased
      ascorbate (ASA + DHA) content correlated with the increase in gene expression in
      its biosynthetic pathway, especially the putative gene of GDP-l-galactose
      phosphorylase VTC2. Increased cysteine availability combined with increased
      expression of gamma-glutamylcysteine synthetase (GSH1) and glutathione synthetase
      (GSH2) genes allows higher glutathione biosynthesis in response to ozone,
      particularly in Carpaccio. In addition, ozone caused a remobilization of amino
      acids with a decreased pool of total amino acids and an increase of Cys and
      putrescine, especially in Carpaccio. In addition, the expression of genes
      encoding threonine aldolase was strongly induced only in the most tolerant
      genotype, Carpaccio. Reduced ascorbate levels could partly explain the
      sensitivity to ozone for Robusta but not for Cima. Reduced ascorbate level alone
      is not sufficient to account for ozone tolerance in poplar, and it is necessary
      to consider several other factors including glutathione content. 

PMID- 24682618
TI  - Structural development of redwood branches and its effects on wood growth.
AB  - Redwood branches provide all the carbohydrates for the most carbon-heavy forests
      on Earth, and recent whole-tree measurements have quantified trunk growth rates
      associated with complete branch inventories. Providing all of a tree's
      photosynthetic capacity, branches represent an increasing proportion of total
      aboveground wood production as trees enlarge. To examine branch development and
      its effects on wood volume growth, we dissected 31 branches from eight Sequoia
      sempervirens (D. Don) Endl. and seven Sequoiadendron giganteum Lindl. trees. The
      cambium-area-to-leaf-area ratio was maintained with size and age but increased
      with light availability, whereas the heartwood-deposition-area-to-leaf-area ratio
      increased with size and age but was insensitive to light availability. The
      proportion of foliage mass arrayed in <1-cm-diameter epicormic shoots increased
      with decreasing light and was higher in Sequoia (20-60%) than in Sequoiadendron
      (3-16%). Well-illuminated branches concentrated leaves higher and distally, while
      shaded branches distributed leaves lower and proximally. In similar light
      environments, older branches distributed leaves lower and more proximally than
      younger branches. Branch size, light, species, heartwood area, a heartwood-area
      species interaction, and ovulate cone mass predicted 87.5% of the variability in
      wood volume growth of branches. After accounting for the positive effects of size
      and light, wood volume growth declined with heartwood area and age. The effect of
      age was trivial compared to the effect of heartwood area, suggesting that
      heartwood expansion caused the age-related decline in wood volume growth.
      Additionally, Sequoiadendron branches of similar size and light environment with
      more ovulate cones produced less wood, even though these cones were long-lived
      and photosynthetic, reflecting the energetic cost of seed production. These
      results contributed to a conceptual model of branch development in which light
      availability, injury, heartwood content, gravity, and time interact to produce
      the high degree of branch structural variation evident within redwood crowns. 

PMID- 24682620
TI  - Abstracts of the 9th European Lupus Meeting, April 23-26 2014, Athens, Greece.

PMID- 24682619
TI  - Anaplastic astrocytomas: survival and prognostic factors in a surgical series.
AB  - BACKGROUND: To study patient characteristics, prognostic factors and overall
      survival (OS) in a consecutive, surgical series of WHO grade III anaplastic
      astrocytomas (AA). METHODS: Patients were identified from a prospective tumor
      database at Oslo University Hospital, Norway, and patients undergoing surgery for
      an AA from 2005-2012 were included. Patients' medical charts were retrospectively
      reviewed for data collection. RESULTS: A total of 99 adult patients with
      histologically verified AA were included. Median age was 52 years (20-81). Biopsy
      was conducted in 33 % and resection in 67 %. Adjuvant treatment with radiation
      therapy + temozolomide or radiation therapy only was given in 63 % and 26 %,
      respectively. The thirty-day mortality rate was 3 %. Median OS was 19 months (95
      % CI 11-27 months). Age >= 65 years, KPS < 70, biopsy as opposed to resection,
      and no adjuvant treatment were confirmed negative prognostic factors in
      multivariate analysis. For patients undergoing resection, presence of
      postoperative contrast-enhanced tumor, not volume of residual tumor, had
      significant impact on OS in adjusted analysis. CONCLUSIONS: Median OS following
      surgery was 19 months, though much variable outcome was observed among subgroups
      of AA (95 % CI 11-27 months). Age >=65 years, KPS < 70, biopsy as opposed to
      resection, and no adjuvant treatment were confirmed negative prognostic factors
      for OS.

PMID- 24682625
TI  - Adherence to best practice guidelines in chronic spontaneous urticaria (CSU)
      improves patient outcome.

PMID- 24682626
TI  - What happens to mental health treatment during pregnancy? Women's experience with
      prescribing providers.
AB  - This exploratory study completed interviews with 25 depressed pregnant women who
      had prior depression, and when becoming pregnant, were receiving depression
      medication or tried to get mental health care. Seventy one percent of women were
      more than 25 weeks gestation at the time of the interview. Thirty-five percent of
      women were not receiving treatment. While 94 % told their provider of their
      pregnancy, 36 % had no opportunity to discuss the risks and benefits of continued
      pharmacotherapy; 42 % had no opportunity to continue pharmacotherapy. Some
      providers may be reluctant to treat depressed pregnant women, creating a
      potential barrier to their receipt of needed care.

PMID- 24682627
TI  - Suicide, Self-Harm and Survival Strategies in Contemporary Heavy Metal Music: A
      Cultural and Literary Analysis.
AB  - This paper seeks to think creatively about the body of research which claims
      there is a link between heavy metal music and adolescent alienation, self
      destructive behaviours, self-harm and suicide. Such research has been criticised,
      often by people who belong to heavy metal subcultures, as systematically
      neglecting to explore, in a meaningful manner, the psychosocial benefits for
      individuals who both listen to contemporary heavy metal music and socialize in
      associated groups. We argue that notions of survival, strength, community, and
      rebellion are key themes in contemporary heavy metal music. Through literary
      lyrical analysis of a selection of heavy metal tracks, this paper aims to redress
      the balance of risk and benefit. We argue that listening to this type of music,
      the accompanying social relationships, sense of solidarity and even the type of
      dancing can ameliorate tumultuous and difficult emotions. Songs which could be
      read as negative can induce feelings of relief through the sense that someone
      else has felt a particular way and recovered enough to transform these emotions
      into a creative outlet. This genre of music may therefore not increase the risk
      of untoward outcomes in any simple sense but rather represent a valuable resource
      for young people in difficulty. 

PMID- 24682628
TI  - Textual standardization and the DSM-5 "common language".
AB  - In February 2010, the American Psychiatric Association (APA) launched their DSM-5
      website with details about the development of the fifth edition of the Diagnostic
      and Statistical Manual of Mental Disorders (DSM-5). The APA invited "the general
      public" to review the draft diagnostic criteria and provide written comments and
      suggestions. This revision marks the first time the APA has solicited public
      review of their diagnostic manual. This article analyzes reported speech on the
      DSM-5 draft diagnostic criteria for the classification Posttraumatic Stress
      Disorder. It demonstrates how textual standardization facilitates the cultural
      portability of the DSM-5 diagnostic criteria such that a community of speakers
      beyond the borders of the APA come to be seen as exemplary speakers, writers, and
      revisers of the professional style. Furthermore, analysis shows how co-authoring
      practices recontextualize the "voice" and persona of putative patient reported
      speech on Criterion D2. As a consequence of textual standardization, spoken
      discourse becomes recontextualized as the product of scientific inquiry and the
      organization of psychiatric knowledge. 

PMID- 24682629
TI  - Pain sensitivity: an unnatural history from 1800 to 1965.
AB  - Who was truly capable of experiencing pain? In this article, I explore ideas
      about the distribution of bodily sensitivity in patients from the early
      nineteenth century to 1965 in Anglo-American societies. While certain patients
      were regarded as "truly hurting," other patients' distress could be disparaged or
      not even registered as being "real pain." Such judgments had major effects on
      regimes of pain-alleviation. Indeed, it took until the late twentieth century for
      the routine underestimation of the sufferings of certain groups of people to be
      deemed scandalous. Often the categorizations were contradictory. For instance,
      the humble status of workers and immigrants meant that they were said to be
      insensitive to noxious stimuli; the profound inferiority of these same patients
      meant that they were especially likely to respond with "exaggerated" sensitivity.
      How did physicians hold such positions simultaneously? Pain-assignation claimed
      to be based on natural hierarchical schemas, but the great Chain of Feeling was
      more fluid than it seemed. 

PMID- 24682630
TI  - Meta-analysis of randomised trials on laparoscopic versus open surgery for acute
      appendicitis: has firm evidence been reached?

PMID- 24682631
TI  - Robert Whytt (1714-1766): from dropsy in the brain to tuberculous meningitis.
AB  - Robert Whytt was born and educated in Edinburgh and served the City in the Royal
      Infirmary. A prolific author, his major work is usually said to be his Essay on
      the Vital and other Involuntary Movements of Animals (1751), based on his belief
      that a 'sentient principle' was not limited to the nervous system but was
      distributed throughout the body, a view that brought him into conflict with
      Albrecht von Haller, who held that the sentient and motor powers of the body were
      those of a machine. Whatever about the speculative nature of the sentient
      principle, Whytt was a clinician blessed with unusual clarity, and he is
      remembered today for his Observations on the Dropsy in the Brain (1768). Therein
      he described the clinical signs and symptoms of what later came to be recognised
      as tuberculous meningitis, the acute disease which appears early in the haemic
      spread of the infection in a child, and which was fatal until the discovery of
      chemotherapy and antimicrobials. John Cheyne, in describing two terminal cases,
      recognised the connexion between hydrocephalus and scrophula, and Dorothy Price
      provided a precise guide to the clinical picture in 1942. When streptomycin
      became available Christopher McSweeney used it to alter the bleak picture in
      Dublin, and was helped by the prevention resulting from neonatal BCG
      immunisation. Later antimicrobials have facilitated the avoidance of emergent
      bacillary resistance. 

PMID- 24682632
TI  - Reframing medicine's publics: the local as a public of vaccine refusal.
AB  - Although medical and public health practitioners aim for high rates of
      vaccination, parent vaccination concerns confound doctors and complicate doctor
      patient interactions. Medical and public health researchers have studied and
      attempted to counter antivaccination sentiments, but recommended approaches to
      dispel vaccination concerns have failed to produce long-lasting effects. We use
      observations made during a small study in a rural area in a southeastern state to
      demonstrate how a shift away from analyzing vaccination skepticism as a national
      issue with a global remedy reveals the nuances in vaccination sentiments based on
      locality. Instead of seeing antivaccinationists as a distinct public based on
      statistical commonalities, we argue that examining vaccination beliefs and
      practices at the local level offers a fuller picture of the contextualized nature
      of vaccination decisions within the psychosocial spaces of families. A view of
      vaccination that emphasizes the local public, rather than a globally conceived
      antivaccination public, enables medical humanists and rhetoricians to offer
      important considerations for improving communications about vaccinations in
      clinical settings. 

PMID- 24682633
TI  - Re-exploration of the craniotomy after surgical treatment of unruptured
      intracranial aneurysms.
AB  - BACKGROUND: Unplanned re-exploration of the craniotomy after surgical treatment
      of unruptured intracranial aneurysms (UIAs) is sometimes required, but the
      underlying causes and rates of these procedures are seldom reported. This study
      retrospectively analyzed the causes of such re-explorations to identify methods
      for decreasing their necessity. METHOD: From January 2000 to December 2011, 1,720
      patients with a total of 1,938 UIAs underwent surgical treatment at our
      institution. From this cohort, 26 patients (1.5 %) with 38 UIAs required re
      exploration. Clinical data, aneurysm characteristics, treatment methods, and the
      incidence and causes of re-exploration of the craniotomy were analyzed for these
      26 patients. RESULTS: Several causes of re-exploration were identified:
      compromised distal blood flow (eight patients, 0.47 %), hemorrhagic venous
      infarction (four patients, 0.23 %), brain retraction injury (three patients, 0.17
      %), newly identified aneurysms (three patients, 0.17 %), bleeding from an
      incompletely clipped aneurysm (two patients, 0.12 %), epidural hematoma (two
      patients, 0.12 %), failed aneurysm clipping (two patients, 0.12 %) and other
      causes (two patients, 0.12 %). Annual re-exploration incidence rates ranged from
      0 to 3.1 %. Annual incidence rates gradually decreased following the introduction
      of several intraoperative monitoring systems. CONCLUSIONS: Precise surgical
      planning and careful operative techniques can reduce the incidence of unplanned
      re-exploration of the craniotomy. The introduction of various intraoperative
      monitoring systems can also contribute to a reduction in this incidence.

PMID- 24682634
TI  - How to distinguish tumor growth from transient expansion of vestibular
      schwannomas following Gamma Knife radiosurgery.
AB  - BACKGROUND: Typically, vestibular schwannomas (VS) react to Gamma Knife
      radiosurgery (GKRS) with a transient increase of tumor volume owed to tumor
      swelling at about 6 months followed by a reduction of tumor volume owed to tumor
      shrinkage at about 18 months. It is important to distinguish this transient tumor
      expansion (TTE) from tumor growth. We undertook this study to see if there is a
      typical time interval in the follow-up of VS following GKRS, which may indicate
      tumor growth rather than TTE. METHODS: We retrospectively reviewed the patient
      charts of patients who underwent GKRS for unilateral sporadic VS at the Gamma
      Knife Center Zurich from 1994-2009 and who were treated by J. Siegfried or one of
      the authors (TM). Tumor progression was defined as an increase of tumor volume of
      >= 20 % as compared to the initial tumor volume at the earliest 2 years following
      GKRS. This time interval of >= 2 years was chosen in order to distinguish TTE
      from genuine tumor progression. Whenever tumor enlargement was suspected on
      follow-up MRI at >= 2 years following GKRS, tumor volumes were measured using
      custom software. RESULTS: From 1994-2009, 235 patients underwent GKRS in Zurich
      for unilateral sporadic VS. Tumor progression with a volume increase of >= 20 %
      occurred in 21/235 (8.9 %) patients at 3.4 +/- 0.9 years following GKRS.
      Seventeen out of 235 (7 %) patients had a clinically relevant tumor progression
      requiring microsurgery or repeat radiosurgery. CONCLUSIONS: According to our
      data, time may be a good parameter distinguishing tumor progression due to tumor
      growth from TTE due to tumor swelling in VS following GKRS. Tumor growth seems to
      occur at about 3-4 years following GKRS for VS as opposed to TTE, which seems to
      be present at about 6-18 months following GKRS for VS.

PMID- 24682635
TI  - Supratentorial calcified pseudotumour: experience of a single institution and
      review of the literature.
AB  - BACKGROUND: Calcified pseudotumours (CPTs) are rarely found in the central
      nervous system (CNS). Information on supratentorial CPT is limited. We add our
      experience treating three supratentorial CPTs. Clinical presentation,
      pathological findings and clinical course are discussed, and a literature review
      is provided. METHOD: Between September 2011 and December 2012, three patients
      (age range 33-60 years) were diagnosed with symptomatic supratentorial CPTs, for
      which they underwent resection. Their clinical, radiological, and surgical data
      were retrospectively retrieved from their medical records and reported. RESULTS:
      Symptoms at presentation included headache (n = 1), blurred vision (n = 1), and
      cognitive decline (n = 1). One tumour was in the left frontal lobe very close to
      the convexity surface, and the other two were in the midline adjacent to the
      corpus callosum. Radiological features included a calcified mass on computerised
      tomography (n = 3), a hypointense (n = 2) or hyperintense (n = 1) signal on T2
      and a rim of enhancement with some non-homogenous lesional enhancement on T1
      gadolinium (Gd) sequences on magnetic resonance imaging (n = 2). Two patients
      underwent gross total resection and had an uneventful postoperative course. The
      third underwent partial removal due to the tumour's adherence to adjacent
      vascular structures and suffered postoperative complications. On pathology, all
      lesions had low cellularity fibrovascular tissue mixed with lobules of a
      haematoxylinophilic, chondromyxoid-like matrix surrounded at its periphery by a
      variable layer of palisading spindle, epithelioid or multinucleated giant cells.
      All three CPTs had focal inflammatory infiltrates and variable degrees of
      metaplastic calcification and ossification. CONCLUSIONS: Surgical removal is
      recommended for benign intracranial CPTs that are symptomatic, are associated
      with brain oedema, or show tumour growth. Stable and asymptomatic CPTs can be
      followed.

PMID- 24682636
TI  - The use of the Burden Assessment Scale with families of a pediatric population.
AB  - The emotional, financial and social impact on caregivers of those with pediatric
      psychiatric, emotional and behavioral disorders has been poorly documented. This
      study sought to begin to remedy this by determining the utility of the Burden
      Assessment Scale (BAS) with this population. 300 parents seeking services within
      a major Canadian city were interviewed using the BAS and a follow up
      questionnaire on the clarity, comprehensiveness and acceptability of the BAS. The
      BAS was clear, acceptable and comprehensive for >80% of participants. Factor
      analysis revealed four factors compared to the original five factors found with
      adults. The BAS had a utility with this population and would be a valuable
      addition to standard information gathered but use of the total score only is
      recommended.

PMID- 24682637
TI  - Partial likelihood estimation of IRT models with censored lifetime data: an
      application to mental disorders in the ESEMeD surveys.
AB  - Developmental studies of mental disorders based on epidemiological data are often
      based on cross-sectional retrospective surveys. Under such designs, observations
      are right-censored, causing underestimation of lifetime prevalences and
      correlations, and inducing bias in latent trait models on the observations. In
      this paper we propose a Partial Likelihood (PL) method to estimate unbiased IRT
      models of lifetime predisposition to develop a certain outcome. A two-step
      estimation procedure corrects the IRT likelihood of outcome appearance with a
      function depending on (a) projected outcome frequencies at the end of the risk
      period, and (b) outcome censoring status at the time of the observation.
      Simulation results showed that the PL method yielded good recovery of true
      frequencies and intercepts. Slopes were best estimated when events were
      sufficiently correlated. When PL is applied to lifetime mental health disorders
      (assessed in the ESEMeD project surveys), estimated univariate prevalences were,
      on average, 1.4 times above raw estimates, and 2.06 higher in the case of
      bivariate prevalences. 

PMID- 24682638
TI  - Sampling plans for pest mites on physic nut.
AB  - The starting point for generating a pest control decision-making system is a
      conventional sampling plan. Because the mites Polyphagotarsonemus latus and
      Tetranychus bastosi are among the most important pests of the physic nut
      (Jatropha curcas), in the present study, we aimed to establish sampling plans for
      these mite species on physic nut. Mite densities were monitored in 12 physic nut
      crops. Based on the obtained results, sampling of P. latus and T. bastosi should
      be performed by assessing the number of mites per cm(2) in 160 samples using a
      handheld 20* magnifying glass. The optimal sampling region for T. bastosi is the
      abaxial surface of the 4th most apical leaf on the branch of the middle third of
      the canopy. On the abaxial surface, T. bastosi should then be observed on the
      side parts of the middle portion of the leaf, near its edge. As for P. latus, the
      optimal sampling region is the abaxial surface of the 4th most apical leaf on the
      branch of the apical third of the canopy on the abaxial surface.
      Polyphagotarsonemus latus should then be assessed on the side parts of the leaf's
      petiole insertion. Each sampling procedure requires 4 h and costs US$ 7.31.

PMID- 24682639
TI  - Polycyclic aromatic hydrocarbons (PAHs) in starfish body and bottom sediments in
      Mohang Harbor (Taean), South Korea.
AB  - The concentrations of 27 polycyclic aromatic hydrocarbons (PAHs) were determined
      in bottom sediments and starfish from Mohang Harbor (MH) in Taean peninsula,
      South Korea. In December 2007, crude oil washed ashore from the M/V Hebei Spirit
      and was subsequently cleaned up within a few months of the incident. The
      ecological risk, bioaccumulation factor (BAF), and composition of the 27 PAHs
      were examined. The PAH concentrations in the bottom sediment ranged from 24 to
      366 MUg/kg dried weight, and the ecological risk was determined as minimal (mERL
      Q < 1). Total PAH concentrations in Asterina pectinifera (inside seawall) and
      Asterias amurensis (outside seawall) were 1,226 and 1,477 MUg/kg dry weight
      (d.w.), respectively. The total BAFs (?BAF) for A. amurensis was 3.8 times higher
      than that of A. pectinifera, and the PAH concentrations of 5-6 log K OW were
      highest in the two starfish species. Further, PAH fingerprint analysis (nine
      alkyl-substituted PAHs fraction, low molecular weight (LMW)/high molecular weight
      (HMW), Phe/Ant, and Flu/Pyr), and principal component analysis (PCA) based on
      three crude oil samples from the M/V Hebei Spirit showed no remaining influence
      of crude oil. 

PMID- 24682640
TI  - Assessment of the bioavailability of cadmium in Jamaican soils.
AB  - Extraordinary geogenic concentrations of cadmium (Cd) have been reported for some
      Jamaican soils. However, the bioavailability of the metal in these soils remains
      unknown. Here, the bioavailability of Cd in selected Jamaican soils was
      investigated through the determination of total and sequentially extractable
      concentrations in paired soil-plant (yam; Dioscorea sp.) samples (n = 24), using
      neutron activation analysis and atomic absorption spectroscopy as primary
      analytical techniques. Our results indicate that total soil Cd varied widely (2.2
      148.7 mg kg(-1)), and on average, total extractable Cd accounted for ~55 % of the
      total soil Cd. The exchangeable and oxidizable species averaged 1.5 and 6.4 % of
      the total Cd, respectively, and, based on Spearman analysis, are the best
      predictors of yam Cd. There is also good evidence to suggest that variation in
      the bioavailability of the metal is in part controlled by the geochemical
      characteristics of the soils analyzed and is best explained by pH, cation
      exchange capacity (CEC) and organic matter content (% LOI). 

PMID- 24682641
TI  - Evaluation of usefulness of Microbial Assay for Risk Assessment (MARA) in the
      cyanobacterial toxicity estimation.
AB  - The aim of the study was to elucidate the usefulness of the Microbial Assay for
      Risk Assessment (MARA) to evaluate toxicity in samples containing cyanobacterial
      products. Cyanobacterial extracts with different cyanotoxin contents and pure
      cyanotoxins-microcystin-LR, cylindrospermopsin and anatoxin-a-were tested. On the
      basis of the microbial reaction, MARA indicated only slight or no toxicity in the
      studied extracts. Similarly, no or low toxicity of pure toxins was detected at
      the concentrations used (up to 10 MUg/ml). Weak relationships between the
      reactions of individual organisms exposed to cyanotoxin-containing extracts and
      to the same pure toxins were observed. On the other hand, inhibition of some
      organisms, such as Pichia anomalia, whose growth was not impacted by pure
      cyanotoxins, indicated the presence of other biologically active compounds in the
      studied extracts. In conclusion, MARA assay is not enough sensitive to be used as
      a good tool for cyanotoxin screening. It may, however, be applied in searching
      for antimicrobial/antifungal cyanobacteria-derived compounds. 

PMID- 24682642
TI  - [Scabies: A world plague].
AB  - Scabies is a ubiquitous contagious disease, and its prevalence is growing.
      Diagnostic difficulties vary according to the patient's age and health. Benzyl
      benzoate and ivermectin are the reference drugs in France. Decontamination of the
      patients' bedding, clothing, and environment is essential for successful
      treatment. 

PMID- 24682643
TI  - THz time scale structural rearrangements and binding modes in lysozyme-ligand
      interactions.
AB  - Predicting the conformational changes in proteins that are relevant for substrate
      binding is an ongoing challenge in the aim of elucidating the functional states
      of proteins. The motions that are induced by protein-ligand interactions are
      governed by the protein global modes. Our measurements indicate that the detected
      changes in the global backbone motion of the enzyme upon binding reflect a shift
      from the large-scale collective dominant mode in the unbound state towards a
      functional twisting deformation that assists in closing the binding cleft.
      Correlated motion in lysozyme has been implicated in enzyme function in previous
      studies, but detailed characterization of the internal fluctuations that enable
      the protein to explore the ensemble of conformations that ultimately foster large
      scale conformational change is yet unknown. For this reason, we use THz
      spectroscopy to investigate the picosecond time scale binding modes and
      collective structural rearrangements that take place in hen egg white lysozyme
      (HEWL) when bound by the inhibitor (NAG)3. These protein thermal motions
      correspond to fluctuations that have a role in both selecting and sampling from
      the available protein intrinsic conformations that communicate function. Hence,
      investigation of these fast, collective modes may provide knowledge about the
      mechanism leading to the preferred binding process in HEWL-(NAG)3. Specifically,
      in this work we find that the picosecond time scale hydrogen-bonding
      rearrangements taking place in the protein hydration shell with binding modify
      the packing density within the hydrophobic core on a local level. These
      localized, intramolecular contact variations within the protein core appear to
      facilitate the large cooperative movements within the interfacial region
      separating the alpha- and beta- domain that mediate binding. The THz time-scale
      fluctuations identified in the protein-ligand system may also reveal a molecular
      mechanism for substrate recognition.

PMID- 24682644
TI  - Public voices in pharmaceutical deliberations: negotiating "clinical benefit" in
      the FDA's Avastin Hearing.
AB  - This article offers a hybrid rhetorical-qualitative discourse analysis of the
      FDA's 2011 Avastin Hearing, which considered the revocation of the breast cancer
      indication for the popular cancer drug Avastin. We explore the multiplicity of
      stakeholders, the questions that motivated deliberations, and the kinds of
      evidence presented during the hearing. Pairing our findings with contemporary
      scholarship in rhetorical stasis theory, Mol's (2002) construct of multiple
      ontologies, and Callon, Lascoumes, and Barthe's (2011) "hybrid forums," we
      demonstrate that the FDA's deliberative procedures elides various sources of
      evidence and the potential multiplicity of definitions for "clinical benefit."
      Our findings suggest that while the FDA invited multiple stakeholders to offer
      testimony, there are ways that the FDA might have more meaningfully incorporated
      public voices in the deliberative process. We conclude with suggestions for how a
      true hybrid forum might be deployed. 

PMID- 24682645
TI  - Beyond prevention: containment rhetoric in the case of bug chasing.
AB  - Bug chasing, the practice of pursuing HIV positive sexual partners in order to
      acquire HIV, presents multiple dilemmas for health affiliates in terms of how to
      address discourses and practices that challenge widely held beliefs about health
      and medicine. In order to examine how researchers respond to controversial
      counterpublic rhetorics, this essay chronicles the construction of "bug chasing"
      in published social science literature. Guided by a theory of containment
      rhetoric, I analyze how bug chasers are configured in the language of social
      science used to describe and explain them. I find that social scientific coverage
      of bug chasing often addresses the behavior using a recipe of rhetorical
      containment: first, authors gaze upon bug chasers via distanced descriptions of
      the community; second, authors characterize the behavior as exhibiting an
      idealistic naivete; and, third, authors stress the inconceivable, and therefore
      reproachable, sacrifice that bug chasing ultimately demands of its onlookers and
      participants. In closing, I evaluate the consequences of this containment
      rhetoric and offer three rhetorical maneuvers to aid future scholarship that
      examines the discourses and communities that counter dominant health ideologies. 

PMID- 24682646
TI  - Differences in breastfeeding initiation by maternal diabetes status and race,
      Ohio 2006-2011.
AB  - To examine breastfeeding trends at hospital discharge from 2006 to 2011 by
      diabetes status and to determine associations between diabetes status and
      breastfeeding. Ohio Vital Statistics birth certificate data from 2006 to 2011,
      including all singleton births to Ohio resident mothers of reproductive age (16
      44 years), were used to analyze trends in breastfeeding by diabetes status
      [prepregnancy diabetes (PDM), gestational diabetes (GDM)]. Logistic regression
      was used to evaluate the relationship between breastfeeding at discharge and
      diabetes type. Because a significant interaction between diabetes status and race
      existed, the model was stratified by race. This study includes 803,222 Ohio
      births from 2006 to 2011. A significant, increasing trend of breastfeeding (P <
      .0001) existed among women with GDM (63-70 %) and no DM (62-69 %). GDM
      breastfeeding rates were frequently the highest, while women with PDM often had
      the lowest breastfeeding initiation rates, regardless of sample characteristic.
      In models stratified by race, Black women were often the least likely to
      breastfeed, but overweight or obese and diabetes were not associated with a
      decreased likelihood of breastfeeding as they were among White women. While
      breastfeeding rates have increased in Ohio, they have still not reached the
      Healthy People 2020 goals. Our study shows that breastfeeding initiation rates
      vary by diabetes status and race. This study can aid in tailoring breastfeeding
      intervention and counseling efforts to women least likely to initiate
      breastfeeding, such as women with pregnancy diabetes, to improve the health of
      both infants and mothers.

PMID- 24682647
TI  - Myostatin knockdown and its effect on myogenic gene expression program in stably
      transfected goat myoblasts.
AB  - Myostatin, a negative regulator of skeletal muscle mass, is a proven candidate to
      modulate skeletal muscle mass through targeted gene knockdown approach. Here, we
      report myostatin (MSTN) knockdown in goat myoblasts stably expressing small
      hairpin RNA (shRNAs) against MSTN gene through lentivirus vector-mediated
      integration. We observed 72% (p = 0.003) and 54% (p = 0.022) downregulation of
      MSTN expression with sh2 shRNA compared to empty vector control and untransduced
      myoblasts, respectively. The knockdown of MSTN expression was accompanied with
      concomitant downregulation of myogenic regulatory factor MYOD (77%, p = 0.001),
      MYOG (94%, p = 0.000), and MYF5 (36%, p = 0.000), cell cycle regulator p21 (62%,
      p = 0.000), MSTN receptor ACVR2B (23%, p = 0.061), MSTN antagonist follistatin
      (81%, p = 0.000), and downstream signaling mediators SMAD2 (20%, p = 0.060) and
      SMAD3 (49%, p = 0.006). However, the expression of MYF6 was upregulated by 14%
      compared to control lentivirus-transduced myoblasts (p = 0.354) and 79% compared
      to untransduced myoblasts (p = 0.018) in sh2 shRNA-transduced goat myoblasts
      cells. Although, MSTN knockdown led to sustained cell proliferation of myoblasts,
      the myoblasts fusion was suppressed in both MSTN knocked down and control
      lentivirus-transduced myoblasts. The expression of interferon response gene OAS1
      was significantly upregulated in control lentivirus (10.86-fold; p = 0.000)- and
      sh2 (1.71-fold; p = 0.002)-integrated myoblasts compared to untransduced
      myoblasts. Our study demonstrates stable knockdown of MSTN in goat myoblasts
      cells and its potential for use in generation of transgenic goat by somatic cell
      nuclear transfer.

PMID- 24682648
TI  - Routine contrast esophagram has minimal impact on the postoperative management of
      patients undergoing esophagectomy for esophageal cancer.
AB  - BACKGROUND: Routine contrast esophagram is frequently performed after
      esophagectomy in order to detect occult anastomotic leak (AL). This modality has
      a low sensitivity, and its routine use has been called into question.
      Accordingly, we sought to demonstrate the clinical impact of routine contrast
      esophagography in the management of patients undergoing esophagectomy for
      malignant disease. METHODS: All patients undergoing esophagectomy from 2005 to
      2011 for malignancy at a North American University hospital were identified from
      a prospectively collected database. Barium esophagram (BE) was performed within
      the first week postoperatively. Patients were dichotomized according to whether
      they had an AL, and the sensitivity and specificity of BE was determined. The
      clinical impact of the BE result, defined as cessation of enteral feeding,
      additional interventions, or delay in discharge, was determined. RESULTS:
      Overall, 221 patients underwent esophagectomy. Thirty (13.6 %) developed an AL,
      of which 10 (30 %) had a positive BE, 12 (40 %) had a negative BE, and 8 (26.7 %)
      had no BE and were diagnosed clinically (1/8), by computed tomography (CT) (3/8),
      endoscopically (3/8), or at reoperation (1/7). AL in patients with a negative BE
      was confirmed clinically (4/12), by CT (6/12), endoscopically (1/12), or at
      reoperation (1/12). The sensitivity and specificity of BE was 45.5 and 97.8 %,
      respectively. BE altered postoperative management in 8/221 (3.6 %) patients, with
      5/221 (2.3 %) undergoing therapeutic intervention. Conversely, 3/221 (1.4 %)
      patients demonstrated clinically insignificant AL, delaying discharge and feeding
      without intervention. CONCLUSION: Contrast esophagram is not an effective
      screening modality for AL when employed routinely following esophagectomy.

PMID- 24682649
TI  - Regional delivery of oncolytic vaccinia virus: it's time for clinical trials.

PMID- 24682650
TI  - Proceedings of the 2014 annual meeting, April 30-May 4, 2014, Las Vegas, NV.

PMID- 24682651
TI  - The costs and benefits of self-monitoring for higher functioning children and
      adolescents with autism.
AB  - The ability to regulate behaviors and emotions depends in part on the ability to
      flexibly monitor one's own progress toward a goal. Atypical patterns of response
      monitoring have been reported in individuals with autism spectrum disorders
      (ASD). In the current study we examined the error related negativity (ERN), an
      electrophysiological index of response monitoring, in relation to behavioral,
      social cognitive, and emotional presentation in higher functioning children (8-16
      years) diagnosed with autism (HFA: N = 38) and an age- and IQ-matched sample of
      children without autism (COM: N = 36). Both HFA and COM participants displayed
      larger amplitude responses to error compared to correct response trials and these
      amplitudes did not differ by diagnostic group. For participants with HFA, larger
      ERN amplitudes were associated with more parent-reported autistic symptoms and
      more self-reported internalizing problems. However, across the full sample,
      larger ERN amplitudes were associated with better performance on theory of mind
      tasks. The results are discussed in terms of the utility of electrophysiological
      measures for understanding essential moderating processes that contribute to the
      spectrum of behavioral expression in the development of ASD.

PMID- 24682652
TI  - Can autism spectrum disorders and social anxiety disorders be differentiated by
      the social responsiveness scale in children and adolescents?
AB  - Autism spectrum disorder (ASD) as well as social phobia (SP), and selective
      mutism (SM) are characterised by impaired social interaction. We assessed the
      validity of the Social Responsiveness Scale (SRS) to differentiate between ASD,
      and SP/SM. Raw scores were compared in 6-18 year old individuals with ASD (N =
      60), SP (N = 38), SM (N = 43), and typically developed (N = 42). Sensitivity and
      specificity were examined. The three disorders showed overlapping SRS scores.
      Especially in boys with SM (ROC-AUC = .81), presence of ASD was overestimated by
      the SRS. A combination of three disorder specific questionnaires resulted in
      marginally improved diagnostic accuracy. For the clinically very relevant
      differential diagnosis of SP/SM, SRS results must be interpreted with caution. 

PMID- 24682654
TI  - Ado-trastuzumab emtansine (T-DM1): a novel antibody-drug conjugate for the
      treatment of HER2-positive metastatic breast cancer.
AB  - Human epidermal growth factor receptor-2 (HER2)-positive breast cancer is an
      aggressive form of breast cancer associated with poorer prognosis and shortened
      survival. Primary and acquired resistance to existing HER2-targeted therapies
      presents a challenge for the management of patients with HER2-positive metastatic
      breast cancer. Ado-trastuzumab emtansine, a drug-antibody conjugate, has shown
      promising results for patients failing prior treatment with trastuzumab. Ado
      trastuzumab emtansine consists of the monoclonal antibody trastuzumab linked to a
      potent microtubule inhibitor (emtansine), allowing a targeted delivery of
      chemotherapy to cells that overexpress HER2. Ado-trastuzumab emtansine has been
      approved for use in patients with metastatic breast cancer who have failed prior
      therapy with trastuzumab and a taxane. Although well-tolerated in clinical
      trials, thrombocytopenia has been reported and platelet values should be
      monitored closely. Increased liver enzymes and bilirubin, as well as
      cardiotoxicity, have also been documented, and recommendations for dose reduction
      or discontinuation due to these toxicities are available. Clinical trials are
      currently ongoing to further define the role of ado-trastuzumab emtansine in both
      the metastatic and early breast cancer settings. 

PMID- 24682655
TI  - HER2 and TOP2A amplification in a hospital-based cohort of breast cancer
      patients: associations with patient and tumor characteristics.
AB  - Gene amplification is an important factor for altered gene expression in breast
      cancers. TOP2A-amplification often occurs concomitantly with HER2 amplification,
      and it has been suggested to be predictive for the response to anthracycline
      chemotherapy. This study assessed the correlation between HER2 status and TOP2A
      co-amplification, the possible association of TOP2A single-nucleotide
      polymorphisms with the frequency of this co-amplification as well as confirmation
      of association with outcome. HER2 and TOP2A amplification were analyzed in a
      tissue microarray from a clinical cohort study. Additionally, a common genetic
      variant (rs13695) in the TOP2A gene was genotyped in germline DNA. HER2 gene
      amplification was compared with HER2-IHC findings assessed during clinical
      routine work, and the association between all the biomarkers analyzed and the
      clinical outcome was determined. As an exploratory aim, rs13695 genotypes were
      compared with TOP2A amplification status. HER2 amplification was seen in 101 of
      628 (16.1 %) and TOP2A amplification in 32 (5.1 %) cancers. No TOP2A
      amplification occurred without HER2 co-amplification. HER2 amplification was
      found in 8, 13.6, and 55.1 % of patients with HER2-IHC 0/1+, 2+, and 3+ tumors,
      respectively. HER2-IHC was not associated with an effect on the prognosis, but
      HER2-FISH was. There was an association between the rs13695 genotype and TOP2A
      amplification status (P = 0.03). Although there was a significant correlation
      between HER2 status determined by IHC and HER2 by FISH, only HER2 gene
      amplification status by FISH was correlated with outcome indicating greater
      utility for FISH in routine clinical settings.

PMID- 24682656
TI  - Accuracy of ultrasound-guided breast-conserving surgery in the determination of
      adequate surgical margins.
AB  - The goal of this study was to assess the size of the ultrasound-measured margin
      associated with an adequate surgical margin during breast-conserving surgery
      (BCS). The study was designed as a prospective cohort study. Patients with
      primary invasive breast cancer undergoing BCS were included. The ultrasound
      measured surgical margins were compared with the pathological margins. 147
      patients were eligible for analysis. 21 (14.3 %) patients had close or positive
      resection margins and 13 (8.8 %) underwent a second operation. Small excision
      volume, multifocality, postmenopausal status, high grade tumor-associated
      intraductal component, and invasion of lymph vessels and lymph nodes were
      associated with increased risk of positive excision margins. In the study cohort,
      882 Ultrasonography (US) margins were measured and a good correlation to the
      pathological margins was observed. Overestimation of the US-measured margins
      relative to the pathological margins was increased with younger age,
      premenopausal status, and intraductal component. The estimated positive and
      negative predictive values, sensitivity and specificity were 81.0, 96.2, 48.4,
      and 99.1 %, respectively. We found that a sonographically estimated margin of >=
      4 mm was associated with an adequate pathological margin of >= 1 mm in 100 % of
      tumors that did not have a high grade intraductal component. However, this was
      not applicable for tumor-associated high grade intraductal component where a US
      margin of 14 mm was associated with clear pathological margins in 100 % of cases.
      Intraoperative ultrasonography is a safe and feasible method to obtain clear
      surgical margins by BCS.

PMID- 24682653
TI  - Canonical BMP-Smad signalling promotes neurite growth in rat midbrain
      dopaminergic neurons.
AB  - Ventral midbrain (VM) dopaminergic (DA) neurons project to the dorsal striatum
      via the nigrostriatal pathway to regulate voluntary movements, and their loss
      leads to the motor dysfunction seen in Parkinson's disease (PD). Despite recent
      progress in the understanding of VM DA neurogenesis, the factors regulating
      nigrostriatal pathway development remain largely unknown. The bone morphogenetic
      protein (BMP) family regulates neurite growth in the developing nervous system
      and may contribute to nigrostriatal pathway development. Two related members of
      this family, BMP2 and growth differentiation factor (GDF)5, have neurotrophic
      effects, including promotion of neurite growth, on cultured VM DA neurons.
      However, the molecular mechanisms regulating their effects on DA neurons are
      unknown. By characterising the temporal expression profiles of endogenous BMP
      receptors (BMPRs) in the developing and adult rat VM and striatum, this study
      identified BMP2 and GDF5 as potential regulators of nigrostriatal pathway
      development. Furthermore, through the use of noggin, dorsomorphin and BMPR/Smad
      plasmids, this study demonstrated that GDF5- and BMP2-induced neurite outgrowth
      from cultured VM DA neurons is dependent on BMP type I receptor activation of the
      Smad 1/5/8 signalling pathway. 

PMID- 24682658
TI  - Total choline and choline-containing moieties of commercially available pulses.
AB  - Estimating dietary choline intake can be challenging due to missing foods in the
      current United States Department of Agriculture (USDA) database. The objectives
      of the study were to quantify the choline-containing moieties and the total
      choline content of a variety of pulses available in North America and use the
      expanded compositional database to determine the potential contribution of pulses
      to dietary choline intake. Commonly consumed pulses (n = 32) were analyzed by
      hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC
      MS/MS) and compared to the current USDA database. Cooking was found to reduce the
      relative percent from free choline and increased the contribution of
      phosphatidylcholine to total choline for most pulses (P < 0.05). Using the
      expanded database to estimate choline content of recipes using pulses as meat
      alternatives, resulted in a different estimation of choline content per serving
      (+/-30%), compared to the USDA database. These results suggest that when pulses
      are a large part of a meal or diet, the use of accurate food composition data
      should be used.

PMID- 24682657
TI  - Anthocyanins inhibit lipogenesis during adipocyte differentiation of 3T3-L1
      preadipocytes.
AB  - Anthocyanins have been shown to suppress body weight and fat mass in animal
      studies. However, the effect of anthocyanins on the process of lipid accumulation
      during adipocyte differentiation is not fully understood and the lipogenic
      transcription factors regulated by anthocyanins have not been identified. We
      investigated the effects of anthocyanins on lipogenesis pathways during adipocyte
      differentiation in 3T3-L1 cells. Anthocyanins reduced triglyceride (TG)
      accumulation in a dose-dependent manner during adipocyte differentiation.
      Accumulation of TG was rapidly reversed by anthocyanin withdrawal. Anthocyanins
      markedly reduced gene and protein expression levels of lipogenic transcription
      factors such as liver X receptor alpha, sterol regulatory element-binding protein
      1c, peroxisome proliferators-activated receptor-gamma, and CCAAT enhancer-binding
      protein-alpha. In addition, the target gene and protein expression of these
      lipogenic transcription factors such as fatty acid synthase, stearoyl-CoA
      desaturase-1, and acetyl-CoA carboxylase alpha were markedly suppressed by
      anthocyanins. Thus, anthocyanins suppress lipid accumulation in adipocytes due to
      broad inhibition of the transcription factors regulating lipogenesis. This may
      partially explain the mechanism by which anthocyanins exert their anti-obesity
      effect. 

PMID- 24682659
TI  - Use of red blood cell membranes to evaluate the antioxidant potential of plant
      extracts.
AB  - Antioxidant phytochemicals in fruits and vegetables of a vegetarian diet may
      account for the reduced risk of aging and stress oxidative associated diseases.
      In this study, a simple, rapid and accurate new bioassay for the determination of
      the antioxidant activity of purified or crude plant extracts and thier
      interactions is described, based on the fluorimetric determination of
      thiobarbituric acid reactive substances (TBARS) released by UV-B radiated red
      blood cell (RBC) ghosts. Pure resveratrol, white and red wine and pomegranate
      juice (PJ) were used as antioxidant source to test the biological method. TBARS
      production is a function of radiation time, the number of RBC ghosts in the
      radiated sample and the loaded antioxidant. The antioxidant activity of
      resveratrol was detected at a submicromolar concentration range [0.02 MUg/mL-0.1
      MUmol/L]. The activity of red wine was almost 10 times higher than that of white
      wine, and PJ juice had the highest activity. Submaximal protective effects of PJ
      and red wine were additive. 

PMID- 24682661
TI  - Irrigation water quality and the benefits of implementing good agricultural
      practices during tomato (Lycopersicum esculentum) production.
AB  - The implementation of good agricultural practices (GAP) from irrigation water to
      the tomato packaging process enhances the safety of fresh produce and its value
      throughout the food chain. The aim of the present study was to show that fresh
      produce farms that apply and enforce GAP could reduce the presence of Salmonella
      in finished produce. Samples were collected biweekly from six packing houses from
      the central region of Sinaloa, Mexico, for the isolation of Salmonella spp by the
      ISO 6579:2002 method, and the isolated strains were serotyped and genotyped by
      the Kauffmman-White scheme and pulsed field gel electrophoresis (PFGE),
      respectively. Salmonella strains were detected in 13 (36.1 %) irrigation water
      samples, while only two tomato samples were positive (5.5 %). Eight different
      serotypes were identified in irrigation water, and Salmonella Oranienburg (34 %)
      was the most prevalent; however, only Salmonella Agona and Salmonella Weltevreden
      were present on tomatoes. Salmonella Oranienburg was the most widely dispersed
      and variable serotype, with 10 different PFGE profiles. Salmonella Weltevreden
      was isolated from both types of samples, albeit with distinct genetic profiles,
      implying that the sources of contamination differ. These results confirm the
      utility of implementing good agricultural practices to reduce Salmonella
      contamination in irrigation water and the packaging process. 

PMID- 24682660
TI  - Diabetes and hemochromatosis.
AB  - The common form of hereditary hemochromatosis is an autosomal recessive disorder
      most prevalent in Caucasians that results in excessive iron storage. The clinical
      manifestations of hemochromatosis are protean. HFE genotype, which determines the
      degree of iron overload and duration of disease have profound effects on disease
      expression. The prevalence of diabetes in this population has likely been
      underestimated because of studies that include a broad range of ethnicities and
      associating diabetes with allele frequency in spite of the decreased risk of
      diabetes in heterozygotes compared with homozygotes. Loss of insulin secretory
      capacity is likely the primary defect contributing to development of diabetes
      with insulin resistance playing a secondary role. Phlebotomy can ameliorate the
      defects in insulin secretion if initiated early. Screening a select population of
      individuals with type 2 diabetes may identify patients with hemochromatosis early
      and substantially impact individual clinical outcomes. 

PMID- 24682662
TI  - Dissipation kinetics and effect of different decontamination techniques on the
      residues of emamectin benzoate and spinosad in cowpea pods.
AB  - Dissipation and decontamination of the semisynthetic macrolide emamectin benzoate
      and the natural insecticide spinosad on cowpea pods were studied following field
      application at single and double doses of 11.0 and 22 and 73 and 146 g ai ha(-1),
      respectively. Residues of these naturalytes were estimated using LC-MS/MS. The
      initial deposit of 0.073 and 0.153 mg kg(-1) of emamectin benzoate dissipated
      below quantitation level on the fifth and seventh day at single and double
      dosage, respectively. For spinosad, the initial deposits of 0.94 and 1.90 mg kg(
      1) reached below quantitation level on the 7th day and 15th day at single and
      double dosage, respectively. The half-life of emamectin benzoate and spinosad was
      1.13-1.49 and 1.05-1.39 days with the calculated safe waiting period of 2.99-6.12
      and 1.09-3.25 days, respectively, for single and double dosage. Processing of the
      harvestable pods with different decontamination techniques resulted in 33.82 to
      100 % removal 2 h after the application of emamectin benzoate and 100 % removal 3
      days after spraying, while the removal was 42.05 to 87.46 % 2 h after the
      application of spinosad and 38.05 to 68.08 % 3 days after application. 

PMID- 24682663
TI  - Low-molecular-weight inhibitors of cell differentiation enable efficient growth
      of mouse iPS cells under feeder-free conditions.
AB  - Embryonic stem cells and induced pluripotent stem (iPS) cells are usually
      maintained on feeder cells derived from mouse embryonic fibroblasts (MEFs). In
      recent years, the cell culture of iPS cells under serum- and feeder-free
      conditions is gaining attention in overcoming the biosafety issues for clinical
      applications. In this study, we report on the use of multiple small-molecular
      inhibitors (i.e., CHIR99021, PD0325901, and Thiazovivin) to efficiently cultivate
      mouse iPS cells without feeder cells in a chemically-defined and serum-free
      condition. In this condition, we showed that mouse iPS cells are expressing the
      Nanog, Oct3/4, and SSEA-1 pluripotent markers, indicating that the culture
      condition is optimized to maintain the pluripotent status of iPS cells. Without
      these small-molecular inhibitors, mouse iPS cells required the adaptation period
      to start the stable cell proliferation. The application of these inhibitors
      enabled us the shortcut culture method for the cellular adaptation. This study
      will be useful to efficiently establish mouse iPS cell lines without MEF-derived
      feeder cells. 

PMID- 24682664
TI  - Spectrum disorders, social stressors and suicide: the impact on service
      utilisation.

PMID- 24682665
TI  - Swan song for schizophrenia?

PMID- 24682666
TI  - ICD, DSM and the Tower of Babel.

PMID- 24682668
TI  - Sensory impairments and their associations with functional disability in a sample
      of the oldest-old.
AB  - PURPOSE: Research focusing on the consequences of sensory impairments for the
      everyday competence of the oldest-old is emerging. The two main goals of this
      study were to document the prevalence of self-reported vision, hearing, and dual
      sensory impairment and to explore associations of these impairments with
      functional disability in near-centenarians and centenarians. METHODS:
      Centenarians and near-centenarians (N = 119; average age = 99) were recruited,
      with about 80% living in the community. In-person interviews included self
      ratings of vision and hearing impairment and functional disability conceptualized
      as having difficulties performing personal and instrumental activities of daily
      livings (PADLs and IADLs). RESULTS: Based on self-report ratings, 17% of
      participants were classified as having a visual impairment only, 18% as having a
      hearing impairment only, and 38% with both a visual and hearing impairment (dual
      sensory impairment). Regression analyses demonstrated that having a vision
      impairment only and being dual sensory impaired were the strongest predictors of
      functional disability. They were associated with higher levels of functional
      disability over and above higher levels of depressive symptomatology,
      interference of health with desired activities, and living in a nursing home.
      CONCLUSIONS: Sensory impairments-especially dual sensory impairment-are prevalent
      in the oldest-old. Having dual sensory impairment or a single visual impairment
      among other factors are strongly associated with less-optimal everyday
      functioning in the oldest-old.

PMID- 24682669
TI  - Improving the mapping of condition-specific health-related quality of life onto
      SF-6D score.
AB  - BACKGROUND: This study sought to improve the predicative performance and goodness
      of-fit of mapping models, as part of indirect valuation, by introducing cubic
      spline smoothing to map a group of health-related quality of life (HRQOL)
      measures onto a preference-based measure. METHODS: This study was a secondary
      analysis of a cross-sectional health survey data assessing the HRQOL for patients
      with colorectal neoplasms. Mapping functions of condition-specific functional
      assessment of cancer therapy-colorectal (FACT-C) onto preference-based SF-6D
      measure were developed using a dataset of 553 Chinese subjects with different
      stages of colorectal neoplasm. The missing values of FACT-C were imputed using
      multiple imputation. Then three widely applicable models (ordinary least square
      (OLS), Tobit and two-part models) were employed for the mapping function after
      applying the cubic spline smoothing on the data. For the evaluation of the
      effectiveness of cubic spline smoothing and multiple imputation, the goodness-of
      fit and prediction performance of each model were compared. RESULTS: Analyses
      showed that the models fitted with transformed data from cubic spline smoothing
      offered better performance in goodness-of-fit and prediction than the models
      fitted with the original data. The values of [Formula: see text] were improved by
      over 10%, and the root mean square error and the mean absolute error were both
      reduced. The best goodness-of-fit and performance were achieved by OLS model
      using transformed data from cubic spline smoothing. CONCLUSIONS: Cubic spline
      smoothing and multiple imputation were recommended for the mapping of HRQOL
      measures onto the preference-based measure. Among the three mapping models, the
      simple-to-use OLS model had the best performance.

PMID- 24682667
TI  - Highly efficient neutralization by plasma antibodies from human immunodeficiency
      virus type-1 infected individuals on antiretroviral drug therapy.
AB  - Little is known about the neutralizing antibodies induced in HIV-1 patients on
      antiretroviral treatment, which constitute an interesting group of individuals
      with improved B cell profile. Plasma samples from 34 HIV-1 seropositive
      antiretroviral drug treated (ART) patients were tested for neutralization against
      a panel of 14 subtype-A, B and C tier 1 and tier 2 viruses in TZM-bl assay. Of
      the 34 plasma samples, remarkably all the plasma samples were able to neutralize
      at least one virus while 32 (94 %) were found to neutralize >=50 % viruses
      tested. In terms of overall neutralization frequency, approximately 86 %, 68 %
      and 17 % of the virus/plasma combinations showed 50 % neutralizing activity at 1
      > 60, 1 >= 200 and 1 >= 2000 dilutions respectively. The improvement in
      neutralizing activity was shown to be associated with ART in two follow up
      patients. The neutralization of viruses by two representative plasma samples,
      AIIMS221 and AIIMS265, was exclusively mediated by immunoglobulin G fractions
      independent of ART drugs and IgG retained cross-reactive binding to recombinant
      gp120 proteins. We observed a positive trend of neutralization with duration of
      ART (p = 0.06), however no such correlation was found with clinical and
      immunological variables like CD4 count (p = 0.35), viral load (p = 0.09) and
      plasma total IgG (p = 0.46). Our study suggests that the plasma antibodies from
      ART patients display high neutralizing activity most likely due to an improved B
      cell function induced by ART despite low antigenic stimulation.

PMID- 24682670
TI  - Designing an architectural style for dynamic medical Cross-Organizational
      Workflow management system: an approach based on agents and web services.
AB  - This paper shows how the combined use of agent and web services technologies can
      help to design an architectural style for dynamic medical Cross-Organizational
      Workflow (COW) management system. Medical COW aims at supporting the
      collaboration between several autonomous and possibly heterogeneous medical
      processes, distributed over different organizations (Hospitals, Clinic or
      laboratories). Dynamic medical COW refers to occasional cooperation between these
      health organizations, free of structural constraints, where the medical partners
      involved and their number are not pre-defined. More precisely, this paper
      proposes a new architecture style based on agents and web services technologies
      to deal with two key coordination issues of dynamic COW: medical partners finding
      and negotiation between them. It also proposes how the proposed architecture for
      dynamic medical COW management system can connect to a multi-agent system
      coupling the Clinical Decision Support System (CDSS) with Computerized Prescriber
      Order Entry (CPOE). The idea is to assist the health professionals such as
      doctors, nurses and pharmacists with decision making tasks, as determining
      diagnosis or patient data analysis without stopping their clinical processes in
      order to act in a coherent way and to give care to the patient. 

PMID- 24682671
TI  - Usability evaluation of Laboratory and Radiology Information Systems integrated
      into a hospital information system.
AB  - This study was conducted to evaluate the usability of widely used laboratory and
      radiology information systems. Three usability experts independently evaluated
      the user interfaces of Laboratory and Radiology Information Systems using
      heuristic evaluation method. They applied Nielsen's heuristics to identify and
      classify usability problems and Nielsen's severity rating to judge their
      severity. Overall, 116 unique heuristic violations were identified as usability
      problems. In terms of severity, 67 % of problems were rated as major and
      catastrophic. Among 10 heuristics, "consistency and standards" was violated most
      frequently. Moreover, mean severity of problems concerning "error prevention" and
      "help and documentation" heuristics was higher than of the others. Despite
      widespread use of specific healthcare information systems, they suffer from
      usability problems. Improving the usability of systems by following existing
      design standards and principles from the early phased of system development life
      cycle is recommended. Especially, it is recommended that the designers design
      systems that inhibit the initiation of erroneous actions and provide sufficient
      guidance to users.

PMID- 24682672
TI  - [Is too much money harmful for innovation?].
AB  - Significant sums have been allocated to countries to enable them to make
      measurements of HIV viral load available at the level of districts and
      departments. Wanting to make this examination available to all HIV-infected
      patients appears fair, but it is possible to envision other strategies for
      decentralizing this process. It is generally agreed that every additional
      examination entails loss to follow-up and thus to treatment. On the other hand, a
      lack of resources induces more innovation, as demonstrated over the last half
      century for short courses of tuberculosis treatment, combined vaccines, and
      essential and generic drugs. Body weight is the best indicator for monitoring HIV
      viral load. We sought to determine if it is possible to raise awareness of this
      measurement that requires simple resources and provides an immediate result,
      available to healthcare providers in outlying areas. Specifically, we studied the
      measurement of body fat percentage, which appears to be a promising choice. A
      trial conducted in Casamance with an impedance meter incorporated into a
      commercially available scale yielded negative results for this specific task
      (measurement irregularities due to the condition of the soles of the patients'
      feet). It seems important to us to study scientifically the interest of this
      indicator scientifically and its performance in the field pragmatically, with
      more accessible measurement methods, such as skinfold (a method that has been
      demonstrated its efficacy in physical anthropology and in the domain of sports). 

PMID- 24682673
TI  - Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of
      mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways.
AB  - The mechanism of blue light-induced retinal ganglion cell (RGC) injury is poorly
      understood. In this study, we established a patented light-emitting diode-based
      system to study the effects of long-term blue light exposure under culture
      conditions on RGC-5 cells. Long-term blue light exposure significantly reduced
      cell viability in a time-dependent manner and induced apoptosis and necrosis in
      RGC-5 cells. Long-term blue light exposure marked an increase in the expression
      of Bax and active Caspase-3 (p17), which was accompanied by Bcl-2 down
      regulation, and displayed features of the mitochondria-dependent apoptosis
      pathway. Blue light exposure also increased the generation of reactive oxygen
      species (ROS), and was a strong inducer of ROS-sensitive protein nuclear factor
      erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression.
      Moreover, blue light exposure constitutively activated p38 mitogen-activated
      protein kinases and c-Jun NH2-terminal kinase (JNK), as well as induced the
      phosphorylation of extracellular signal-regulated kinase in the early phase, in
      blue light-exposed RGC-5 cells. The protein expression of c-jun and c-fos was
      further enhanced after RGC-5 cells were exposed to blue light. Taken together,
      these findings indicated that blue light induced RGC-5 cell line death in
      dependence upon exposure duration. The potential mechanisms for this phenomenon
      might be via activated mitochondria-dependent apoptosis, increased ROS production
      and protein expressions of Nrf2 and HO-1, and activated JNK/p38 MAPK signaling
      pathways.

PMID- 24682674
TI  - Survival of HER2-positive primary breast cancer patients treated by neoadjuvant
      chemotherapy plus trastuzumab: a multicenter retrospective observational study
      (JBCRG-C03 study).
AB  - We investigated the disease-free survival (DFS) of HER2-positive primary breast
      cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, as well
      as predictive factors for DFS and pathologic response. Data from 829 female
      patients treated between 2001 and 2010 were collected from 38 institutions in
      Japan. Predictive factors were evaluated using multivariate analyses. The 3-year
      DFS rate was 87 % [95 % confidence interval (CI) 85-90]. The pathologic complete
      response (pCR: ypT0/is + ypN0) rate was 51 %. The pCR rate was higher in the
      ER/PgR-negative patients than in the ER/PgR-positive patients (64 vs. 36 %, P <
      0.001). Patients with pCR showed a higher DFS rate than patients without pCR (93
      vs. 82 %, P < 0.001). Multivariate analysis revealed three independent predictors
      for poorer DFS: advanced nodal stage [hazard ratio (HR) 2.63, 95 % CI 1.36-5.21,
      P = 0.004 for cN2-3 vs. cN0], histological/nuclear grade 3 (HR 1.81, 95 % CI 1.15
      2.91, P = 0.011), and non-pCR (HR 1.98, 95 % CI 1.22-3.24, P = 0.005). In the
      ER/PgR-negative dataset, non-pCR (HR 2.63, 95 % CI 1.43-4.90, P = 0.002) and
      clinical tumor stage (HR 2.20, 95 % CI 1.16-4.20, P = 0.017 for cT3-4 vs. cT1-2)
      were independent predictors for DFS, and in the ER/PgR-positive dataset,
      histological grade of 3 (HR 3.09, 95 % CI 1.48-6.62, P = 0.003), clinical nodal
      stage (HR 4.26, 95 % CI 1.53-13.14, P = 0.005 for cN2-3 vs. cN0), and young age
      (HR 2.40, 95 % CI 1.12-4.94, P = 0.026 for <=40 vs. >40) were negative predictors
      for DFS. Strict pCR (ypT0 + ypN0) was an independent predictor for DFS in both
      the ER/PgR-negative and -positive datasets (HR 2.66, 95 % CI 1.31-5.97, P = 0.006
      and HR 3.86, 95 % CI 1.13-24.21, P = 0.029, respectively). These results may help
      assure a more accurate prognosis and personalized treatment for HER2-positive
      breast cancer patients.

PMID- 24682675
TI  - Adolescent physical activity in relation to breast cancer risk.
AB  - Adolescent physical activity may protect against premenopausal breast cancer.
      Whether it also prevents postmenopausal breast cancer, and whether associations
      are independent of adult activity, is unclear. We evaluated this association
      among 75,669 women in the Nurses' Health Study II. In 1997, participants reported
      strenuous, moderate, and walking activity (hours/week) at ages 12-13, 14-17, 18
      22, and 23-29 years. We estimated metabolic equivalent task hours (MET-h)/week.
      Participants also reported current physical activity over follow-up. Breast
      cancer diagnoses (n = 2,697; premenopausal = 1,351; postmenopausal = 965) through
      2011 were reported by participants and confirmed with medical records. We
      additionally stratified analyses by median age at diagnosis. In Cox proportional
      hazards models adjusted for adolescent characteristics, physical activity from
      ages 14-22 was modestly inversely associated with premenopausal breast cancer
      [e.g., hazard ratio (HR) comparing 72+ to <21 MET-h/week 0.81 (95 % confidence
      interval (CI) 0.69-0.95; p-trend = 0.10) for ages 14-17 and 0.85 (95 % CI 0.71
      1.02; p-trend = 0.06 for ages 18-22]. However, adjustment for adult activity and
      additional breast cancer risk factors attenuated the associations [ages 14-17:
      0.85 (95 % CI 0.73-1.00; p-trend = 0.33)]. Associations were stronger among women
      diagnosed at younger ages [e.g., ages 18-22, HR 0.77 (95 % CI 0.60-0.99; p-trend
      = 0.05) for women diagnosed before 46.9 years; HR 1.02 (95 % CI 0.79-1.32; p
      trend = 0.94) for those diagnosed at/after 46.9 years]. Early life physical
      activity was not associated with postmenopausal breast cancer. Overall,
      adolescent physical activity was not associated with breast cancer risk. However,
      we observed a suggestive inverse association of physical activity at ages 14-22
      years with premenopausal breast cancer.

PMID- 24682676
TI  - Additional value of F-18 FDG PET/CT for initial staging in breast cancer with
      clinically negative axillary nodes.
AB  - The aim of this study was to evaluate the clinical impact of the preoperative 18F
      FDG PET/CT in the initial workup of breast cancer with clinically negative
      axillary nodes. Whether the status of the clinical axillary nodal involvement can
      be considered a parameter for making a decision to omit the preoperative 18F-FDG
      PET/CT in the situation reported herein was also determined. A total of 178
      patients who had newly diagnosed breast cancer and for whom the conventional
      diagnostic modalities showed no sign of axillary node metastasis were
      retrospectively enrolled in this study. All the patients underwent preoperative
      18F-FDG PET/CT. The images and histologic results that were obtained were
      analyzed. 18F-FDG PET/CT detected primary lesions in 156 of the 178 patients,
      with an overall sensitivity of 87.6 %, and false negative results were obtained
      for 22 patients (12.4 %). The sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of 18F-FDG PET/CT in the detection
      of axillary nodes were 20.8, 86.9, 37.0, 74.8, and 69.1 %, respectively. Extra
      axillary node metastasis was identified in two patients (1.1 %) who had internal
      mammary nodes. There was no distant metastasis, but coexisting primary tumor was
      detected in five patients (2.8 %). In total, the therapeutic plan was changed
      based on 18F-FDG PET/CT in seven (3.9 %) of the 178 patients, but considering
      only the cases confined to breast cancer, the change occurred in only two
      patients (1.1 %). 18F-FDG PET/CT almost did not affect the initial staging and
      treatment plan in breast cancer with clinically negative axillary node. If the
      axillary node is clinically negative in the preoperative workup of breast cancer,
      then 18F-FDG PET/CT can be omitted.

PMID- 24682677
TI  - Contribution of problem-solving skills to fear of recurrence in breast cancer
      survivors.
AB  - Although fear of recurrence is a major concern among breast cancer survivors
      after surgery, no standard strategies exist that alleviate their distress. This
      study examined the association of patients' problem-solving skills and fear of
      recurrence and psychological distress among breast cancer survivors. Randomly
      selected, ambulatory, female patients with breast cancer participated in this
      study. They were asked to complete the Concerns about Recurrence Scale (CARS) and
      the Hospital Anxiety and Depression Scale. Multiple regression analyses were used
      to examine their associations. Data were obtained from 317 patients. Patients'
      problem-solving skills were significantly associated with all subscales of fear
      of recurrence and overall worries measured by the CARS. In addition, patients'
      problem-solving skills were significantly associated with both their anxiety and
      depression. Our findings warrant clinical trials to investigate effectiveness of
      psychosocial intervention program, including enhancing patients' problem-solving
      skills and reducing fear of recurrence among breast cancer survivors. 

PMID- 24682679
TI  - Anti-epileptic drugs and hormonal treatments.
AB  - OPINION STATEMENT: Epilepsy and the medications used in its treatment are known
      to affect the menstrual cycle, aspects of contraception, and bone health in
      women. Adolescence is an important time to review the diagnosis of both epilepsy
      and the epilepsy syndrome because of the implications and decisions, which should
      be made regarding antiepileptic drug (AED) treatment. In girls, once they are on
      AED therapy, seizure free, and driving, it becomes difficult to change therapy
      because of the risk of breakthrough seizures and the fact that the new AED may
      not be as effective as the first. So a treatment choice made in adolescence is
      often life-long. Therefore, women need to be started on an AED that currently
      appears to be the most suitable for their seizure type, has a low teratogenic
      risk, and hopefully does not interact with contraception. There are no
      contraindications to the use of non-hormonal methods of contraception in women
      with epilepsy. Nonenzyme-inducing AEDs (valproate, benzodiazepines, ethosuximide,
      levetiracetam, tiagabine, and zonisamide) do not show any interactions with the
      combined oral contraceptive. There are interactions between the combined oral
      contraceptive and hepatic microsomal-inducing AEDs (phenytoin, barbiturates,
      carbamazepine, topiramate [dosages >200 mg/day], oxcarbazepine, eslicarbazepine
      and perampanel [dosages >12 mg/day]) and lamotrigine. Women taking enzyme
      inducing AEDs should be encouraged to use a method of contraception that is
      unaffected by their epilepsy medication. Interactions between AEDs and other
      hormonal therapies are less well studied. Studies have suggested that women with
      epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia. No
      studies have been undertaken looking at preventative therapies for these
      comorbidities. This article will concentrate on current contraceptive treatment
      options in patients taking AEDs.

PMID- 24682678
TI  - Electro-oxidation of the dye azure B: kinetics, mechanism, and by-products.
AB  - In this work, the electrochemical degradation of the dye azure B in aqueous
      solutions was studied by electrochemical advanced oxidation processes (EAOPs),
      electro-Fenton, and anodic oxidation processes, using Pt/carbon-felt and boron
      doped diamond (BDD)/carbon-felt cells with H2O2 electrogeneration. The higher
      oxidation power of the electro-Fenton (EF) process using BDD anode was
      demonstrated. The oxidative degradation of azure B by the electrochemically
      generated hydroxyl radicals ((*)OH) follows a pseudo-first-order kinetics. The
      apparent rate constants of the oxidation of azure B by (*)OH were measured
      according to pseudo-first-order kinetic model. The absolute rate constant of
      azure B hydroxylation reaction was determined by competition kinetics method and
      found to be 1.19 * 10(9) M(-1) s(-1). It was found that the electrochemical
      degradation of the dye leads to the formation of aromatic by-products which are
      then oxidized to aliphatic carboxylic acids before their almost mineralization to
      CO2 and inorganic ions (sulfate, nitrate, and ammonium). The evolution of the TOC
      removal and time course of short-chain carboxylic acids during treatment were
      also investigated.

PMID- 24682682
TI  - Role of doxycycline in Clostridium difficile infection acquisition.
AB  - OBJECTIVE: To evaluate and review the literature surrounding the potential
      protective benefit of tetracyclines, particularly doxycycline, in reducing
      Clostridium difficile infection (CDI) acquisition. DATA SOURCES: MEDLINE/PubMed,
      Google Scholar, and International Pharmaceutical Abstracts were searched through
      January 2014 using the search terms doxycycline, tetracycline, and Clostridium
      difficile. STUDY SELECTION AND DATA EXTRACTION: Relevant studies, case reports,
      and review articles were screened for inclusion. Bibliographies of articles were
      extensively reviewed for additional sources. DATA SYNTHESIS: Doxycycline is a
      second-generation tetracycline antibiotic indicated for use in a variety of
      clinical syndromes and has activity against aerobic Gram-positive and -negative,
      anaerobic, and atypical bacteria as well as protozoan parasites. Although not
      used therapeutically to treat CDI, doxycycline may prevent or attenuate the
      virulence factors of toxigenic C difficile. Current literature does not indicate
      an increased risk of development of CDI with doxycycline use. In 3 retrospective
      studies, the use of doxycycline was associated with a protective effect.
      CONCLUSIONS: Doxycycline has been shown to have potential protective effects
      against the development of CDI. Although further randomized placebo-controlled
      studies are needed, available data suggest that the use of doxycycline in place
      of alternative antimicrobials, when appropriate, may be a useful antimicrobial
      stewardship strategy aimed at reducing the incidence of CDI.

PMID- 24682681
TI  - Correlating interleukin-12 stimulated interferon-gamma production and the absence
      of ectodermal dysplasia and anhidrosis (EDA) in patients with mutations in NF
      kappaB essential modulator (NEMO).
AB  - OBJECTIVE: Patients with hypomorphic mutations in Nuclear Factor-kappaB Essential
      Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia
      and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with
      and without EDA. METHODS: PBMCs of NEMO-ID patients, four with EDA carrying
      E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del
      and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-gamma,
      TNF and IL-1beta. The production of various cytokines was measured in the
      supernatants. Fifty-nine healthy individuals served as controls. RESULTS: PBMCs
      of NEMO-ID patients without EDA produce subnormal amounts of IFN-gamma after
      stimulation with PHA, but normal amounts of IFN-gamma after PHA plus IL-12p70. In
      contrast, IFN-gamma production by patients with EDA was low in both cases.
      Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1beta than
      controls, whereas the production of these cytokines by patients without EDA was
      normal. CONCLUSION: Responses of PBMCs in NEMO-ID patients with EDA to PHA with
      and without IL-12p70 appear less robust than in NEMO-ID patients without EDA.
      This possibly indicates a better preserved NEMO function in our patients without
      EDA.

PMID- 24682683
TI  - Selected Abstracts presented at the 10th Annual Meeting of the
      Hematology/Oncology Pharmacy Association, 26-29 March 2014, New Orleans,
      Louisiana, USA.

PMID- 24682684
TI  - Protection circuits for very high frequency ultrasound systems.
AB  - The purpose of protection circuits in ultrasound applications is to block noise
      signals from the transmitter from reaching the transducer and also to prevent
      unwanted high voltage signals from reaching the receiver. The protection circuit
      using a resistor and diode pair is widely used due to its simple architecture,
      however, it may not be suitable for very high frequency (VHF) ultrasound
      transducer applications (>100 MHz) because of its limited bandwidth. Therefore, a
      protection circuit using MOSFET devices with unique structure is proposed in this
      paper. The performance of the designed protection circuit was compared with that
      of other traditional protection schemes. The performance characteristics measured
      were the insertion loss (IL), total harmonic distortion (THD) and transient
      response time (TRT). The new protection scheme offers the lowest IL (-1.0 dB),
      THD (-69.8 dB) and TRT (78 ns) at 120 MHz. The pulse-echo response using a 120
      MHz LiNbO3 transducer with each protection circuit was measured to validate the
      feasibility of the protection circuits in VHF ultrasound applications. The
      sensitivity and bandwidth of the transducer using the new protection circuit
      improved by 252.1 and 50.9 %, respectively with respect to the protection circuit
      using a resistor and diode pair. These results demonstrated that the new
      protection circuit design minimizes the IL, THD and TRT for VHF ultrasound
      transducer applications.

PMID- 24682685
TI  - Fred Apple.

PMID- 24682686
TI  - A 70-year-old man with blue skin.

PMID- 24682687
TI  - Commentary.

PMID- 24682688
TI  - Commentary.

PMID- 24682689
TI  - A case of green blood.

PMID- 24682690
TI  - Positive propylene glycol result in a patient with ethylene glycol poisoning.

PMID- 24682691
TI  - A two-pronged approach.

PMID- 24682692
TI  - Hypothetical structure of prostate-specific antigen.

PMID- 24682693
TI  - Physician writers: Anton Chekhov.

PMID- 24682695
TI  - Ciclosporin in canine dermatology: a decade of comfort.

PMID- 24682694
TI  - Selective alpha(1)-adrenoceptor blockade prevents fructose-induced hypertension.
AB  - The purpose of this study was to investigate the effect of chronic treatment with
      prazosin, a selective alpha1-adrenoceptor antagonist, on the development of
      hypertension in fructose-fed rats (FFR). High-fructose feeding and treatment with
      prazosin (1 mg/kg/day via drinking water) were initiated simultaneously in male
      Wistar rats. Systolic blood pressure, fasted plasma parameters, insulin
      sensitivity, plasma norepinephrine (NE), uric acid, and angiotensin II (Ang II)
      were determined following 9 weeks of treatment. FFR exhibited insulin resistance,
      hyperinsulinemia, hypertriglyceridemia, and hypertension, as well as elevations
      in plasma NE and Ang II levels. Treatment with prazosin prevented the rise in
      blood pressure without affecting insulin levels, insulin sensitivity, uric acid,
      or Ang II levels, while normalizing plasma NE levels in FFR. These data suggest
      that over-activation of the sympathetic nervous system, specifically alpha1
      adrenoceptors, contributes to the development of fructose-induced hypertension,
      however, this over-activation does not appear to an initial, precipitating event
      in FFR. 

PMID- 24682696
TI  - Life-long diseases need life-long treatment: long-term safety of ciclosporin in
      canine atopic dermatitis.
AB  - Ciclosporin (Atopica; Novartis Animal Health) has been licensed for canine atopic
      dermatitis (AD) since 2002. Adverse events (AEs) have been reported in 55 per
      cent of 759 dogs in 15 clinical trials, but are rare in pharmacovigilance data
      (71.81 AEs/million capsules sold). Gastrointestinal reactions were most common,
      but were mild and rarely required intervention. Other AEs were rare (<=1 per cent
      in clinical trials; <10/million capsules sold). Hirsutism, gingival hyperplasia
      and hyperplastic dermatitis were rarely significant and resolved on dose
      reduction. Ciclosporin decreases staphylococcal and Malassezia infections in AD,
      and at the recommended dose is not a risk factor for other infections, neoplasia,
      renal failure or hypertension. The impact on glucose and calcium metabolism is
      not clinically significant for normal dogs. Concomitant treatment with most drugs
      is safe. Effects on cytochrome P450 and MDR1 P-glycoprotein activity may elevate
      plasma ciclosporin concentrations, but short-term changes are not clinically
      significant. Monitoring of complete blood counts, urinalysis or ciclosporin
      levels is not justified except with higher than recommended doses and/or long
      term concurrent immunosuppressive drugs. Ciclosporin is not a contraindication
      for killed (including rabies) vaccines, but the licensed recommendation is that
      live vaccination is avoided during treatment. In conclusion, ciclosporin has a
      positive risk-benefit profile for the long-term management of canine AD. 

PMID- 24682697
TI  - Ciclosporin 10 years on: indications and efficacy.
AB  - Ciclosporin is a lipophilic cyclic polypeptide with powerful immunosuppressive
      and immunomodulatory properties that has been used in veterinary medicine for two
      decades. It is a calcineurin inhibitor whose principal mode of action is to
      inhibit T cell activation. The drug is principally absorbed from the small
      intestine and is metabolised in the intestine and liver by the cytochrome P450
      enzyme system. Ciclosporin is known to interact with a wide range of
      pharmacological agents. Numerous studies have demonstrated good efficacy for the
      management of canine atopic dermatitis and this has been a licensed indication
      since 2003. In addition to the treatment of atopic dermatitis, it has been used
      as an aid in the management of numerous other dermatological conditions in
      animals including perianal fistulation, sebaceous adenitis, pododermatitis,
      chronic otitis externa and pemphigus foliaceus. This article reviews the mode of
      action, pharmacokinetics, indications for use and efficacy of ciclosporin in
      veterinary dermatology. 

PMID- 24682698
TI  - Independent predictors for bladder outcomes after treatment of intravesical
      recurrence following radical nephroureterectomy in patients with primary upper
      tract urothelial carcinoma.
AB  - BACKGROUND: Few studies have described the clinical courses and outcomes in the
      bladder after treatment of intravesical recurrence after radical
      nephroureterectomy (RNU) in patients with primary upper tract urothelial
      carcinoma (UTUC). We investigated the indicators for predicting subsequent
      bladder outcomes after treatment of intravesical recurrence after RNU. METHODS: A
      total of 241 patients with primary UTUC (pTa-4N0M0) who experienced intravesical
      recurrence after RNU were included. Of these patients, 101 (41.9 %) underwent
      Bacillus Calmette-Guerin treatments, whereas 49 (20.3 %) underwent intravesical
      chemotherapy. The median follow-up period after initial transurethral resection
      of the bladder tumor was 33 months. Relationships with bladder outcomes were
      analyzed by using multivariable analysis. RESULTS: Ninety-six patients
      experienced intravesical recurrence, and bladder progression was observed in 13.
      Cumulative incidence rates of intravesical recurrence at 1 and 5 years after
      treatment of the first intravesical recurrence were 31.0 and 48.4 %, whereas
      those of bladder progression at 1 and 5 years thereafter were 2.4 and 8.0 %.
      Multivariate analysis showed that the number of recurrent tumors and pT1 tumors
      at the time of the first intravesical relapse were independent risk factors for
      subsequent intravesical recurrence. With respect to bladder progression,
      multivariate analysis showed that pT1 tumors, the appearance of concomitant
      carcinoma-in situ at the time of the first intravesical relapse, and the absence
      of the Bacillus Calmette-Guerin treatment were independent risk factors.
      CONCLUSIONS: This retrospective study presents a detailed picture of further
      bladder outcomes after intravesical recurrence after RNU in primary UTUC
      patients. The results may assist physicians to develop a more rational protocol
      in bladder surveillance.

PMID- 24682699
TI  - In vitro selection of RNA aptamers directed against protein E: a Haemophilus
      influenzae adhesin.
AB  - Protein E (PE) of Haemophilus influenzae is a highly conserved ubiquitous surface
      protein involved in adhesion to and activation of epithelial cells. The host
      proteins-vitronectin, laminin, and plasminogen are major targets for PE-dependent
      interactions with the host. To identify novel inhibitory molecules of PE, we used
      an in vitro selection method based on systematic evolution of ligands by
      exponential enrichment known as SELEX in order to select 2'F-modified RNA
      aptamers that specifically bind to PE. Fourteen selection cycles were performed
      with decreasing concentrations of PE. Sequencing of clones from the 14th
      selection round revealed the presence of semiconserved sequence motifs in loop
      regions of the RNA aptamers. Among these, three aptamers showed the highest
      affinity to PE in electrophoretic mobility shift assays and in dot blots. These
      three aptamers also inhibited the interaction of PE with vitronectin as revealed
      by ELISA. Moreover, pre-treatment of H. influenzae with the aptamers
      significantly inhibited binding of vitronectin to the bacterial surface. Biacore
      experiments indicated that one of the aptamers had a higher binding affinity for
      PE as compared to the other aptamers. Our results show that it is possible to
      select RNA inhibitors against bacterial adhesins using SELEX in order to inhibit
      interactions with target proteins.

PMID- 24682700
TI  - The roles of autophagy in development and stress responses in Arabidopsis
      thaliana.
AB  - Autophagy is a dynamic process that involves the recycling process of the
      degradation of intracellular materials. Over the past decade, our molecular and
      physiological understanding of plant autophagy has greatly been increased. Most
      essential autophagic machineries are conserved from yeast to plants. The roles
      that autophagy-related genes (ATGs) family play in the lifecycle of the
      Arabidopsis are proved to be similar to that in mammal. Autophagy is activated
      during certain stages of development, senescence or in response to starvation, or
      environmental stress in Arabidopsis. In the progression of autophagy, ATGs act as
      central signaling regulators and could develop sophisticated mechanisms to
      survive when plants are suffering unfavorable environments. It will facilitate
      further understanding of the molecular mechanisms of autophagy in plant. In this
      review, we will discuss recent advances in our understanding of autophagy in
      Arabidopsis, areas of controversy, and highlight potential future directions in
      autophagy research.

PMID- 24682701
TI  - Wickerhamiella kiyanii f.a., sp. nov. and Wickerhamiella fructicola f.a., sp.
      nov., two yeasts isolated from native plants of Atlantic rainforest in Brazil.
AB  - Two novel species, Wickerhamiella kiyanii f.a., sp. nov. (type strain FB1
      1DASP(T) = CBS 12905(T) = CBMAI 1613(T)) and Wickerhamiella fructicola f.a., sp.
      nov. (type strain H10Y(T) = CBS 12902(T) = CBMAI 1614(T)) are proposed in the
      Wickerhamiella clade (Saccharomycetes, Saccharomycetales) to accommodate three
      strains isolated from flowers and fruits typical of the Brazilian Atlantic
      rainforest. The novel status of these yeast species was established by sequence
      divergence observed in the D1/D2 domains of the LSU rRNA gene from the most
      closely related, described species as well as by phylogenetic analysis.
      Wickerhamiella kiyanii sp. nov. differs from its nearest phylogenetic neighbours
      W. pagnoccae CBS 12178(T), Candida jalapaonensis CBS 10935(T) and Candida
      drosophilae CBS 8459(T) by 2.2-4.2% in the D1/D2 sequences. By contrast, a
      sequence divergence of 13.2-13.8% was observed between W. fructicola sp. nov. and
      its closest, described phylogenetic relative Candida kazoui JCM 12558(T) and
      Candida hasegawae JCM 12559(T). Taxonomic descriptions of the two novel species
      are given.

PMID- 24682702
TI  - Pseudozyma brasiliensis sp. nov., a xylanolytic, ustilaginomycetous yeast species
      isolated from an insect pest of sugarcane roots.
AB  - A novel ustilaginomycetous yeast isolated from the intestinal tract of an insect
      pest of sugarcane roots in Ribeirao Preto, Sao Paulo State, Brazil, represents a
      novel species of the genus Pseudozyma based on molecular analyses of the D1/D2
      rDNA large subunit and the internal transcribed spacer (ITS1+ITS2) regions. The
      name Pseudozyma brasiliensis sp. nov. is proposed for this species, with
      GHG001(T) ( = CBS 13268(T) = UFMG-CM-Y307(T)) as the type strain. P. brasiliensis
      sp. nov. is a sister species of Pseudozyma vetiver, originally isolated from
      leaves of vetiver grass and sugarcane in Thailand. P. brasiliensis sp. nov. is
      able to grow well with xylan as the sole carbon source and produces high levels
      of an endo-1,4-xylanase that has a higher specific activity in comparison with
      other eukaryotic xylanases. This enzyme has a variety of industrial applications,
      indicating the great biotechnological potential of P. brasiliensis. 

PMID- 24682703
TI  - Two novel Saccharomycopsis species isolated from black olive brines and a
      tropical plant. Description of Saccharomycopsis olivae f. a., sp. nov. and
      Saccharomycopsis guyanensis f. a., sp. nov. Reassignment of Candida amapae to
      Saccharomycopsis amapae f. a., comb. nov., Candida lassenensis to
      Saccharomycopsis lassenensis f. a., comb. nov. and Arthroascus babjevae to
      Saccharomycopsis babjevae f. a., comb. nov.
AB  - Three yeast strains related to members of the genus Saccharomycopsis were
      isolated. One strain (CLIB 1310) was isolated from olive brines of fermented
      black olives in France and two strains (CLIB 1454 and CLIB 1455) were isolated
      from a plant in French Guiana. Sequence analyses based on the D1/D2 domains of
      the nuclear large subunit rRNA gene, small-subunit rRNA gene and partial EF
      1alpha gene revealed that the strains represented two novel taxa exhibiting
      extensive sequence divergence from the previously described species of the genus
      Saccharomycopsis. Two novel species are described to accommodate these newly
      isolated strains: Saccharomycopsis olivae sp. nov. (type strain CLIB 1310(T) =
      CBS 12701(T)) and Saccharomycopsis guyanensis sp. nov. (type strain CLIB 1455(T)
      = CBS 12914(T) and strain CLIB 1454). Both strains CLIB 1454 and CLIB 1455(T)
      displayed identical sequences but differed in their ability to metabolize
      sorbitol and in their morphology on agar medium. Candida amapae, Candida
      lassensensis and Arthroascus babjevae belonging to the Saccharomycopsis clade,
      are reassigned to Saccharomycopsis as novel combinations. 

PMID- 24682704
TI  - Hymenobacter kanuolensis sp. nov., a novel radiation-resistant bacterium.
AB  - A Gram-reaction-negative, rod-shaped, non-motile, red-pigmented, radiation
      resistant, aerobic bacterium designated T-3(T) was isolated from a soil sample
      from the Qinghai-Tibet Plateau in Tibet, China, after exposure to 10 kGy gamma
      radiation. Phylogenetic analysis based on 16S rRNA sequences indicated that this
      isolate represented a novel member of the genus Hymenobacter. Sequence identities
      of the 16S rRNA gene of strain T-3(T) with the type strains of species of the
      genus Hymenobacter with validly published names range from 89% to 97%, and the
      most closely related species is Hymenobacter psychrotolerans Tibet-IIU11(T)
      (97%). The DNA-DNA relatedness between strain T-3(T) and H. psychrotolerans is
      59.10%. The major fatty acids of strain T-3(T) were iso-C(15 : 0) (27.66%),
      summed feature 4 (iso-C(17 : 1)I and/or anteiso-C(17 : 1)B, 15.84%), anteiso-C(15
      : 0) (14.08%) and summed feature 3 (C(16 : 1)omega7c and/or C(16 : 1)omega6c,
      12.38%). The major menaquinone of strain T-3(T) was MK-7.
      Phosphatidylethanolamine (PE) was predominant in the polar lipid profile. The G+C
      content of the DNA of strain T-3(T) was 69.17 mol%. On the basis of the results
      of the polyphasic characterization presented in this study, it is concluded that
      strain T-3(T) represents a novel species of the genus Hymenobacter, for which the
      name Hymenobacter kanuolensis is proposed. The type strain is T-3(T) ( = ACCC
      05760(T) = KCTC 32407(T)).

PMID- 24682705
TI  - Dietary carotenoids do not improve motility or antioxidant capacity in cichlid
      fish sperm.
AB  - Carotenoids may act as antioxidants under many circumstances. We examined the
      importance of carotenoids as antioxidants in the gonads of male convict cichlids
      (Amatitlania nigrofasciata), a species in which males lack the carotenoid-based
      breeding coloration that characterizes females. Male fish were fed one of four
      diets that included different combinations of xanthophyll and carotene
      carotenoids, and then we measured carotenoid concentration of the gonads,
      gonadosomatic index (GSI), sperm motility, and the antioxidant capacity of the
      gonads. Significant differences were found in gonadal carotenoid content among
      treatment groups, suggesting that dietary carotenoids were indeed sequestered in
      the gonads. There were no differences among diet groups, however, in GSI, sperm
      motility, or gonadal antioxidant capacity. These findings suggest that
      carotenoids are required only in small amounts in the testes of male convict
      cichlids or that they play a limited role in protecting sperm from oxidative
      damage. 

PMID- 24682706
TI  - Brief report: can metrics of reporting bias enhance early autism screening
      measures?
AB  - The goal of the current study was to develop and pilot the utility of two simple
      internal response bias metrics, over-reporting and under-reporting, in terms of
      additive clinical value within common screening practices for early detection of
      autism spectrum disorder risk. Participants were caregivers and children under 36
      months of age (n = 145) participating in first-time diagnostic appointments
      across our clinical research center due to developmental concerns. Caregivers
      were asked to complete the Modified Checklist for Autism in Toddlers (MCHAT) as
      well as a questionnaire embedding six response bias indicator questions. These
      questions were items that in previous clinical studies had been endorsed by an
      overwhelming majority of parents within clinically identified populations.
      Results indicated that removal of self-reports indicative of potential response
      bias dramatically reduced both false positives and false negatives on the MCHAT
      within this sample. This suggests that future work developing internal metrics of
      response bias may be promising in addressing limits of current screening measures
      and practices.

PMID- 24682707
TI  - Interview skills for adults with autism spectrum disorder: a pilot randomized
      controlled trial.
AB  - The purpose of this pilot study was to evaluate the efficacy of the interview
      skills curriculum (ISC), a manualized 12-week group-delivered intervention for
      young adults with autism spectrum disorder (ASD). This intervention aims to
      increase social-pragmatic skills essential to a successful job interview. Twenty
      eight adults (18-36 years) were randomly assigned to one of two groups: ISC or
      waitlist control. Results revealed that the experimental group showed larger
      gains in social-pragmatic skills observed during a mock job interview than the
      control group. Treatment effects on distal outcomes, including social adaptive
      behaviors and depressive symptoms were not significant, although the respective
      effect sizes were medium/large. Results indicate that a brief, low-intensity
      treatment can improve the job-interview performance of young adults with ASD.

PMID- 24682708
TI  - Comparing the teaching interaction procedure to social stories: a replication
      study.
AB  - This study compared the teaching interaction procedure to social stories
      implemented in a group setting to teach social skills to three children diagnosed
      with autism spectrum disorder. The researchers taught each participant one social
      skill with the teaching interaction procedure, one social skill with the social
      story procedure, and one social skill was assigned to a no intervention
      condition. The teaching interaction procedure consisted of didactic questions,
      teacher demonstration, and role-play; the social story procedure consisted of
      reading a book and answering comprehension questions. The researchers measured
      participants' performances during probes, responses to comprehension questions,
      and responding during role-plays. The results indicated that the teaching
      interaction procedure was more efficacious than the social story procedure across
      all three participants. 

PMID- 24682709
TI  - Searching for inhibition of return in the rat using the covert orienting of
      attention task.
AB  - Inhibition of return (IOR) is an important psychological construct describing
      inhibited responses to previously attended locations. In humans, it is
      investigated using Posner's cueing paradigm. This paradigm requires central
      visual fixation and detection of cued stimuli to the left or right of the
      fixation point. Stimuli can be validly or invalidly cued, appearing in the same
      or opposite location to the cue. Although a rat version of the spatial cueing
      paradigm (the covert orienting of attention task) does exist, IOR has so far not
      been demonstrated. We therefore investigated whether IOR could be robustly
      demonstrated in adult male rats using the covert orienting of attention task.
      This task is conducted in holed wall operant chambers with the central three
      holes mimicking the set-up for Posner cueing. Across four samples of rats
      (overall n = 84), we manipulated the following task parameters: stimulus onset
      asynchronies (Experiments 1-3), cue brightness (Experiment 1b) and the presence
      of a central reorienting event (Experiment 4). In Experiment 1, we also
      investigated strain differences by comparing Lister Hooded rats to Sprague-Dawley
      rats. Although Lister Hooded rats briefly showed evidence of IOR (Experiment 1a,
      and see Online Resource 1 data), we were unable to replicate this finding in our
      other experiments using different samples of this strain. Taken together, our
      findings suggest that IOR cannot be robustly demonstrated in the rat using the
      covert orienting of attention task conducted in holed wall operant chambers. 

PMID- 24682710
TI  - Older women's experience with breast cancer treatment decisions.
AB  - The purpose of this study was to better understand older women's experience with
      breast cancer treatment decisions. We conducted a longitudinal study of non
      demented, English-speaking women >= 65 years recruited from three Boston-based
      breast imaging centers. We interviewed women at the time of breast biopsy (before
      they knew their results) and 6 months later. At baseline, we assessed intention
      to accept different breast cancer treatments, sociodemographic, and health
      characteristics. At follow-up, we asked women about their involvement in
      treatment decisions, to describe how they chose a treatment, and influencing
      factors. We assessed tumor characteristics through chart abstraction. We used
      quantitative and qualitative analyses. Seventy women (43 >= 75 years) completed
      both interviews and were diagnosed with breast cancer; 91 % were non-Hispanic
      white. At baseline, women 75+ were less likely than women 65-74 to report that
      they would accept surgery and/or take a medication for >= 5 years if recommended
      for breast disease. Women 75+ were ultimately less likely to receive hormonal
      therapy for estrogen receptor positive tumors than women 65-74. Women 75+ asked
      their surgeons fewer questions about their treatment options and were less likely
      to seek information from other sources. A surgeon's recommendation was the most
      influential factor affecting older women's treatment decisions. In open-ended
      comments, 17 women reported having no perceived choice about treatment and 42
      stated they simply followed their physician's recommendation for at least one
      treatment choice. In conclusion, to improve care of older women with breast
      cancer, interventions are needed to increase their engagement in treatment
      decision-making.

PMID- 24682711
TI  - Microbial diversity, community composition and metabolic potential in hydrocarbon
      contaminated oily sludge: prospects for in situ bioremediation.
AB  - Microbial community composition and metabolic potential have been explored in
      petroleum-hydrocarbon-contaminated sludge of an oil storage facility. Culture
      independent clone library-based 16S rRNA gene analyses revealed that the
      bacterial community within the sludge was dominated by the members of beta
      Proteobacteria (35%), followed by Firmicutes (13%), delta-Proteobacteria (11%),
      Bacteroidetes (10%), Acidobacteria (6%), alpha-Proteobacteria (3%), Lentisphaerae
      (2%), Spirochaetes (2%), and unclassified bacteria (5%), whereas the archaeal
      community was composed of Thermoprotei (54%), Methanocellales (33%),
      Methanosarcinales/Methanosaeta (8%) and Methanoculleus (1%) members. Methyl
      coenzyme M reductase A (mcrA) gene (a functional biomarker) analyses also
      revealed predominance of hydrogenotrophic, methanogenic Archaea (Methanocellales,
      Methanobacteriales and Methanoculleus members) over acetoclastic methanogens
      (Methanosarcinales members). In order to explore the cultivable bacterial
      population, a total of 28 resident strains were identified and characterized in
      terms of their physiological and metabolic capabilities. Most of these could be
      taxonomically affiliated to the members of the genera Bacillus, Paenibacillus,
      Micrococcus, Brachybacterium, Aerococcus, and Zimmermannella, while two strains
      were identified as Pseudomonas and Pseudoxanthomonas. Metabolic profiling
      exhibited that majority of these isolates were capable of growing in presence of
      a variety of petroleum hydrocarbons as sole source of carbon, tolerating
      different heavy metals at higher concentrations (>=1 mM) and producing
      biosurfactant during growth. Many strains could grow under a wide range of pH,
      temperature, or salinity as well as under anaerobic conditions in the presence of
      different electron acceptors and donors in the growth medium. Correlation between
      the isolates and their metabolic properties was estimated by the unweighted pair
      group method with arithmetic mean (UPGMA) analysis. Overall observation indicated
      the presence of diverse groups of microorganisms including hydrocarbonoclastic,
      nitrate reducing, sulphate reducing, fermentative, syntrophic, methanogenic and
      methane-oxidizing bacteria and Archaea within the sludge community, which can be
      exploited for in situ bioremediation of the oily sludge.

PMID- 24682713
TI  - Bone remodelling of the scapula after a total shoulder arthroplasty.
AB  - According to Wolff's law, the changes in stress after a prosthesis implantation
      may modify the shape and internal structure of bone, thus compromising the long
      term prosthesis fixation and, consequently, be a significant factor for glenoid
      loosening. The aim of the present study is to evaluate the changes in the bone
      adaptation process of the scapula after an anatomical and reverse total shoulder
      arthroplasty. Five finite element models of the implanted scapula are developed
      considering the implantation of three anatomical, cemented, all-polyethylene
      components; an anatomical, cementless, metal-backed component; and a reverse, all
      metal component. The methodology followed to simulate the bone adaptation of the
      scapula was previously validated for the intact model, prior to the prosthesis
      implantation. Additionally, the influence of the bone quality on the adaptation
      process is also investigated by considering an osteoporotic condition. The
      results show that the stress shielding phenomenon is more concerning in
      cementless, metal-based components than in cemented, all-polyethylene components,
      regardless of the bone quality. Consequently, as far as the bone adaptation
      process of the bone is concerned, cemented, all-polyethylene components are
      better suited for the treatment of the shoulder joint. 

PMID- 24682712
TI  - Estimation and characterization of unintentionally produced persistent organic
      pollutant emission from converter steelmaking processes.
AB  - Unintentionally produced persistent organic pollutants (UP-POPs) including
      polychlorinated dibenzo-p-dioxins, and dibenzofurans (PCDD/Fs), polychlorinated
      biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) were characterized and
      quantified in stack gas and fly ash from the second ventilation systems in five
      typical converters in five different steelmaking plants. The 2378-substituted
      PCDD/Fs (2378-PCDD/Fs) and dioxin-like PCB (dl-PCBs) toxic equivalents (TEQs)
      were 1.84-10.3 pg WHO-TEQ Nm(-3) in the stack gas and 5.59-87.6 pg WHO-TEQ g(-1)
      in the fly ash, and the PCN TEQs were 0.06-0.56 pg TEQ Nm(-3) in the stack gas
      and 0.03-0.08 pg TEQ g(-1) in the fly ash. The concentrations of UP-POPs in the
      present study were generally lower than those in other metallurgical processes,
      such as electric arc furnaces, iron ore sintering, and secondary metallurgical
      processes. Adding scrap metal might increase UP-POP emissions, indicating that
      raw material composition was a key influence on emissions. HxCDF, HpCDF, OCDF,
      HpCDD, and OCDD were the dominant PCDD/Fs in the stack gas and fly ash. TeCB and
      PeCB were dominant in the stack gas, but HxCB provided more to the total PCB
      concentrations in the fly ash. The lower chlorinated PCNs were dominant in all of
      the samples. The 2378-PCDD/F, dl-PCB, and PCN emission factors in stack gases
      from the steelmaking converter processes (per ton of steel produced) were 1.88
      2.89, 0.14-0.76, and 229-759 MUg t(-1), respectively. 

PMID- 24682715
TI  - Water Uptake Performance of Hygroscopic Heat and Moisture Exchangers after 24
      Hour Tracheostoma Application.
AB  - OBJECTIVE: After total laryngectomy, patients suffer from pulmonary complaints
      due to the shortcut of the upper airways that results in decreased warming and
      humidification of inspired air. Laryngectomized patients are advised to use a
      heat and moisture exchanger (HME) to optimize the inspired air. According to
      manufacturers' guidelines, these medical devices should be replaced every 24
      hours. The aim of this study is to determine whether HMEs still function after 24
      hour tracheostoma application. STUDY DESIGN: Assessment of residual water uptake
      capacity of used HMEs by measuring the difference between wet and dry core
      weight. SETTING: Tertiary comprehensive cancer center. SUBJECTS AND METHODS:
      Three hygroscopic HME types were tested after use by laryngectomized patients in
      long-term follow-up. Water uptake of 41 used devices (including 10 prematurely
      replaced devices) was compared with that of control (unused) devices of the same
      type and with a control device with a relatively low performance. RESULTS: After
      24 hours, the mean water uptake of the 3 device types had decreased compared with
      that of the control devices. For only one type was this difference significant.
      None of the used HMEs had a water uptake lower than that of the low-performing
      control device. CONCLUSION: The water uptake capacity of hygroscopic HEMs is
      clinically acceptable although no longer optimal after 24-hour tracheostoma
      application. From a functional point of view, the guideline for daily device
      replacement is therefore justified.

PMID- 24682714
TI  - Natural autoantibodies to Fcgamma receptors in intravenous immunoglobulins.
AB  - A considerable progress has been achieved in the comprehension of the cellular
      and molecular mechanisms that account for the therapeutic benefit of intravenous
      immunoglobulin (IVIg) in several autoimmune and inflammatory conditions. However,
      the precise mechanisms responsible for such a wide range of biological activities
      have not been proven unambiguously. A wide range of specificities have been
      identified within IVIg including idiotypes of immunoglobulins, T cell receptor,
      HLA molecules, several cell surface molecules of immunological importance such as
      CD4, CD5, Fas, BAFF, cytokines and cytokine receptors, chemokine receptors, CD40
      among others. Here we identify and characterize the natural autoantibodies of IgG
      isotype directed against the human Fc receptors. We show that the F(ab')2 of IVIg
      recognize the FcgammaRIII (CD16) and FcgammaRII (CD32). Interestingly, the
      immunopurified anti-FcgammaIII and anti-FcgammaII antibodies isolated from IVIg
      bind soluble and membrane-bound FcR and inhibit rosette formation. Altogether,
      these results along with previous reports provide pointers on the existence of
      functionally relevant natural autoantibodies towards a wide range of self-motifs
      that may participate in regulation of the immune response. Their presence in the
      therapeutic immunoglobulin preparations may explain at least in part, the
      beneficial effect of IVIg in autoimmune diseases. 

PMID- 24682716
TI  - Human histone acetyltransferase 1 (Hat1) acetylates lysine 5 of histone H2A in
      vivo.
AB  - The primary structure of Histone Acetyltransferase 1 (Hat1) has been conserved
      throughout evolution; however, despite its ubiquity, its cellular function is not
      well characterized. To study its in vivo acetylation pattern and function, we
      utilized shRNAmir against Hat1 expressed in the well-substantiated HeLa (human
      cervical cancer) cell line. To reduce the interference by enzymes with similar
      HAT specificity, we used HeLa cells expressing histone acetyltransferase Tip60
      with mutated acetyl-CoA binding site that abrogates its enzyme activity (mutant
      HeLa-tip60). Two shRNAmir were identified that reduced the expression of the
      cytoplasmic and nuclear forms of Hat1. Cytosolic protein preparations from these
      two clones showed decreased levels of acetylation of lysine 5 (K5) and K12 on
      histone H4, with the concomitant loss of the acetylation of histone H2A at K5.
      This pattern of decreased acetylation of H2AK5 was well defined in preparations
      of histone protein and insoluble nuclear-protein (INP) fractions as well.
      Abrogating the Hat1 expression caused a 74% decrease in colony-forming efficiency
      of mutant HeLa-tip60 cells, reduced the size of the colonies by 50%, and
      decreased the amounts of proteins with molecular weights below 35 kDa in the INP
      fractions.

PMID- 24682719
TI  - Hedgehog signaling between cancer cells and hepatic stellate cells in promoting
      cholangiocarcinoma.
AB  - BACKGROUND: Aberrant Hedgehog (HH) signaling activation is important in cancer
      growth and mediates the interaction between cancer cells and the surrounding
      stromal cells. This study investigated the role of HH signaling on the growth of
      cholangiocarcinoma (CC), focusing on the interaction of CC cells with stromal
      cells. METHODS: To evaluate the interaction between human CC cells (SNU-1196, SNU
      246, SNU-308, SNU-1079, and HuCCT-1) and stromal cells (hepatic stellate cell
      line, Lx-2), co-culture proliferation, migration, and invasion assays were
      performed. In vivo nude mice experiments were conducted using two groups-HuCCT-1
      single implant xenograft (SX) and co-implant xenograft (CX) with HuCCT-1 and Lx
      2. RESULTS: When HuCCT-1 cells were co-cultured with Lx-2 cells, the expression
      of HH signaling-related proteins increased in both HuCCT-1 and Lx-2 cells. Co
      culture with Lx-2 cells stimulated the proliferation, migration, and invasion of
      CC cells, and these effects were mediated by HH signaling. Co-culture of HuCCT-1
      and Lx-2 cells increased the secretion of several cytokines. In an ectopic
      xenograft model, Lx-2 co-implantation increased CC tumor growth and stimulated
      angiogenesis. Cyclopamine attenuated tumor growth in the CX group, but not in the
      HuCCT-1 mono-implant (SX) group. Cyclopamine treatment decreased CC cell
      proliferation, suppressed microvessel density, and increased tumor necrosis in
      the CX group, but not in the SX group. CONCLUSION: Hepatic stellate cells
      stimulate the proliferation, migration, and invasion of CC cells, promote
      angiogenesis through HH signaling activation, and render CC more susceptible to
      necrosis by HH inhibitor.

PMID- 24682717
TI  - Relationship among chelator adherence, change in chelators, and quality of life
      in thalassemia.
AB  - PURPOSE: Thalassemia, a chronic blood disease, necessitates life-long adherence
      to blood transfusions and chelation therapy to reduce iron overload. We examine
      stability of health-related quality of life (HRQOL) in thalassemia and adherence
      to chelation therapy over time, especially after changes in chelator choice.
      METHODS: Thalassemia Longitudinal Cohort participants in the USA, UK, and Canada
      completed the SF-36v2 (ages 14+) and the PF-28 CHQ (parents of children <14
      years). Chelation adherence was defined as self-reported percent of doses
      administered in the last 4 weeks. RESULTS: Two hundred and fifty-eight
      adults/adolescents (mean 29.7 years) and 133 children (mean 8.5 years) completed
      a mean of 2.8-years follow-up. Children made few chelator changes, whereas a mean
      of 2.2 changes was observed among the 37% of adults/adolescents who made chelator
      changes, mainly due to patient preference or medical necessity. Physical HRQOL
      improved among those with lower iron burden (better health status) at baseline
      who made a single change in chelator, but declined among participants with
      multiple changes and/or high iron burden (worse health status). Mental health
      improved among participants with lower iron burden, but iron overload was
      negatively associated with social functioning. Adherence did not significantly
      change over follow-up except for an increase after a change from deferoxamine
      (DFO) infusion to oral deferasirox (p = 0.03). Predictors of lower adherence for
      adults/adolescents at follow-up included side effects, smoking, younger age,
      problems preparing DFO, increased number of days per week DFO prescribed, and
      lower physical quality of life . CONCLUSIONS: Strategies to balance medical needs
      with family, work, and personal life may assist in adherence.

PMID- 24682720
TI  - Suitability of sentinel node mapping as an index of metastasis in early gastric
      cancer following endoscopic resection.
AB  - BACKGROUND: When pathological diagnosis following endoscopic resection (ER) for
      early gastric cancer (EGC) suggests probable lymph node metastasis, additional
      surgery with lymphadenectomy should be performed. The sentinel node (SN) concept
      has yet to be applied to tumors following ER. The aim of this study was to
      evaluate the feasibility of SN navigation surgery for such tumors. METHODS: Forty
      patients diagnosed with EGC lesions <4 cm in diameter underwent gastrectomy with
      SN mapping following ER. A technetium-99 m tin colloid solution and a dye were
      injected into the submucosal layer around the post-ER scar in all four abdominal
      quadrants. We then compared the SN distribution and metastases among the patients
      who underwent ER and controls (n = 192). RESULTS: SNs were identifiable in all
      patients, and the mean number of SNs per case was 4.9. The location of the SN
      basin was similar in the patients who underwent ER and the controls. One patient
      (3 %) whose primary tumor had invaded the submucosal layer had a metastatic SN.
      The median time from ER to surgery was 73 days. No postoperative recurrence was
      observed in any patient over a median follow-up of 1,023 days. CONCLUSIONS: Our
      findings suggest that the SN basin is not greatly affected by ER. The SN concept
      could be suitable for tumors following ER, but conventional gastrectomy with
      lymphadenectomy involving the SN basin should be used at present.

PMID- 24682721
TI  - Quantitative differences between primary and secondary peristaltic contractions
      of the esophagus.
AB  - BACKGROUND AND AIMS: Differences in contraction characteristics between primary
      and secondary peristalsis have only been scarcely studied. Recently new measures
      of contractile activity in the human esophagus were developed. The study aims
      were to use combined manometry and impedance planimetry [pressure-cross-sectional
      area (P-CSA)] recordings from healthy volunteers to examine esophageal
      peristalsis, and, furthermore, to investigate the effect of the motility
      enhancing drug erythromycin to study differential effects on the two types of
      contractions. METHODS: Sixteen healthy volunteers participated in the study [mean
      age 23 (range, 19-34) years, 6 females]. An esophageal probe with a bag for CSA
      measurement was positioned 10 cm above the lower esophageal sphincter. Bag volume
      was increased stepwise from 5 to 25 ml before and after intravenous infusion of
      250 mg erythromycin. Swallow-evoked primary and distension-evoked secondary
      esophageal peristalsis were compared with regard to (1) pressure amplitude, (2)
      CSA amplitude, (3) preload tension (wall tension before an evoked contraction),
      (4) contractile tension, and (5) work outputs. RESULTS: Primary peristalsis
      induced more efficient contractions as the contraction amplitudes, work output
      and contractile tension were higher compared to secondary peristalsis (P <
      0.001). Erythromycin induced change in CSA during distension-evoked secondary
      peristalsis (CSA before 212.9 +/- 26.8 vs. after 180.5 +/- 23.3, P < 0.05). The
      sensitivity to esophageal distension increased with the distending volume both
      before and during erythromycin. The sensitivity was not changed by erythromycin
      (P = 0.6). CONCLUSIONS: Esophageal primary peristaltic contractions were more
      forceful with longer duration, and higher work output compared to secondary
      peristalsis contractions. Erythromycin affected peristalsis only to a minor
      degree.

PMID- 24682722
TI  - Effectiveness and cost-effectiveness of an awareness campaign for colorectal
      cancer: a mathematical modeling study.
AB  - BACKGROUND: A campaign to increase the awareness of the signs and symptoms of
      colorectal cancer (CRC) and encourage self-presentation to a GP was piloted in
      two regions of England in 2011. Short-term data from the pilot evaluation on
      campaign cost and changes in GP attendances/referrals, CRC incidence, and CRC
      screening uptake were available. The objective was to estimate the effectiveness
      and cost-effectiveness of a CRC awareness campaign by using a mathematical model
      which extrapolates short-term outcomes to predict long-term impacts on cancer
      mortality, quality-adjusted life-years (QALYs), and costs. METHODS: A
      mathematical model representing England (aged 30+) for a lifetime horizon was
      developed. Long-term changes to cancer incidence, cancer stage distribution,
      cancer mortality, and QALYs were estimated. Costs were estimated incorporating
      costs associated with delivering the campaign, additional GP attendances, and
      changes in CRC treatment. RESULTS: Data from the pilot campaign suggested that
      the awareness campaign caused a 1-month 10 % increase in presentation rates.
      Based on this, the model predicted the campaign to cost L5.5 million, prevent 66
      CRC deaths and gain 404 QALYs. The incremental cost-effectiveness ratio compared
      to "no campaign" was L13,496 per QALY. Results were sensitive to the magnitude
      and duration of the increase in presentation rates and to disease stage.
      CONCLUSIONS: The effectiveness and cost-effectiveness of a cancer awareness
      campaign can be estimated based on short-term data. Such predictions will aid
      policy makers in prioritizing between cancer control strategies. Future cost
      effectiveness studies would benefit from campaign evaluations reporting as
      follows: data completeness, duration of impact, impact on emergency
      presentations, and comparison with non-intervention regions.

PMID- 24682723
TI  - Use of vaccination in a large outbreak of primary varicella in a detention
      setting for African immigrants.
AB  - BACKGROUND: Primary varicella (PV) presents a public health risk for adults in
      closed residential settings, especially for immigrants from tropical areas where
      infection during childhood is less likely. METHODS: In this study, an outbreak of
      PV at a detention facility for illegal immigrants from Eritrea and Sudan in
      southern Israel is described. Basic demographic information and clinical course
      for all cases were obtained. RESULTS: One hundred and nine cases of PV, all in
      young adult men aged 18-40 years, were diagnosed over a 7-month period (June to
      December 2012). Diagnosed patients were placed in quarantine until the resolution
      of illness without other public health measures being implemented. The Israeli
      Ministry of Health was notified of the outbreak in early December and recommended
      two doses of varicella vaccine for all susceptible detainees and staff. Within 2
      weeks of completion of the first dose of vaccine, there was only one additional
      case in a detainee immunized 13 days prior to diagnosis. The effectiveness of
      vaccination in halting the outbreak was immediate, despite the fact that 15.6% of
      detainees refused to be immunized. CONCLUSIONS: The possible roles of vaccination
      or natural infection in achieving herd immunity and thereby ending the outbreak
      in this population are discussed. We recommend considering early vaccination for
      all when an outbreak or a series of connected cases is detected in a closed
      residential setting such as the detention facility described here.

PMID- 24682724
TI  - CNXeCl and CNXeBr species as halogen bond donors: a quantum chemical study on the
      structure, properties, and nature of halogen...nitrogen interactions.
AB  - In the present study, strength and characteristic of halogen bond interactions
      between CNXeY and NCZ molecules are investigated, where Y = Cl, Br and Z = H, CN,
      F, OH, CH3, OCH3, NH2. MP2/aug-cc-pVTZ calculations indicate that the interaction
      energies for CNXeY?NCZ complexes lie in the range between -1.0 and -3.1 kcal mol
      1. Not surprisingly, the calculated interaction energies show a strong
      correlation with the negative electrostatic potentials on nitrogen atoms. One of
      the most important results of this study is that, according to energy
      decomposition analyses, Cl?N halogen bonds are largely dependent on dispersion
      effects, while electrostatic interactions are the major source of the attraction
      in Br?N bonds. The quantum theory of atoms in molecules (QTAIM) and natural bond
      orbital (NBO) analysis are used in this study to deepen the nature of the
      interactions considered. This appears to be the first report on a halogen bond
      involving halogenated xenon isocyanides.

PMID- 24682725
TI  - Press self-regulation in Britain: a critique.
AB  - This article reviews the history of press self-regulation in Britain, from the
      1947 Ross Commission to the 2012 Leveson Inquiry Commission. It considers the
      history of the Press Council and the Press Complaints Commission, analysing the
      ways they developed, their work, and how they have reached their current non
      status. It is argued that the existing situation in Britain is far from
      satisfactory, and that the press should advance more elaborate mechanisms of self
      control, establishing a new regulatory body called the Public and Press Council
      that will be anchored in law, empowering the new regulator with greater and
      unprecedented authority, and equipping it with substantive sanctioning abilities.
      The Public and Press Council should be independent and effective, with
      transparent policies, processes and responsibilities. Its adjudication should be
      made in accordance with a written, detailed Code of Practice. 

PMID- 24682726
TI  - Inhibition of DNA replication of human papillomavirus by using zinc finger-single
      chain FokI dimer hybrid.
AB  - Previously, we reported that an artificial zinc-finger protein (AZP)
      staphylococcal nuclease (SNase) hybrid (designated AZP-SNase) inhibited DNA
      replication of human papillomavirus type 18 (HPV-18) in mammalian cells by
      binding to and cleaving a specific HPV-18 ori plasmid. Although the AZP-SNase did
      not show any side effects under the experimental conditions, the SNase is
      potentially able to cleave RNA as well as DNA. In the present study, to make AZP
      hybrid nucleases that cleave only viral DNA, we switched the SNase moiety in the
      AZP-SNase to the single-chain FokI dimer (scFokI) that we had developed
      previously. We demonstrated that transfection with a plasmid expressing the
      resulting hybrid nuclease (designated AZP-scFokI) inhibited HPV-18 DNA
      replication in transient replication assays using mammalian cells more
      efficiently than AZP-SNase. Then, by linker-mediated PCR analysis, we confirmed
      that AZP-scFokI cleaved an HPV-18 ori plasmid around its binding site in
      mammalian cells. Finally, a modified MTT assay revealed that AZP-scFokI did not
      show any significant cytotoxicity. Thus, the newly developed AZP-scFokI hybrid is
      expected to serve as a novel antiviral reagent for the neutralization of human
      DNA viruses with less fewer potential side effects.

PMID- 24682727
TI  - Blood flow distribution in an anatomically detailed arterial network model:
      criteria and algorithms.
AB  - Development of blood flow distribution criteria is a mandatory step toward
      developing computational models and numerical simulations of the systemic
      circulation. In the present work, we (i) present a systematic approach based on
      anatomical and physiological considerations to distribute the blood flow in a 1D
      anatomically detailed model of the arterial network and (ii) develop a numerical
      procedure to calibrate resistive parameters in terminal models in order to
      effectively satisfy such flow distribution. For the first goal, we merge data
      collected from the specialized medical literature with anatomical concepts such
      as vascular territories to determine blood flow supply to specific (encephalon,
      kidneys, etc.) and distributed (muscles, skin, etc.) organs. Overall, 28 entities
      representing the main specific organs are accounted for in the detailed
      description of the arterial topology that we use as model substrate. In turn, 116
      vascular territories are considered as the basic blocks that compose the
      distributed organs throughout the whole body. For the second goal, Windkessel
      models are used to represent the peripheral beds, and the values of the resistive
      parameters are computed applying a Newton method to a parameter identification
      problem to guarantee the supply of the correct flow fraction to each terminal
      location according to the given criteria. Finally, it is shown that, by means of
      the criteria developed, and for a rather standard set of model parameters, the
      model predicts physiologically realistic pressure and flow waveforms. 

PMID- 24682728
TI  - PKC in developmental hypothyroid rat brain.
AB  - Thyroid hormone (TH) is essential for the proper development of mammalian central
      nervous system. TH deficiency during the critical period of brain development
      results in permanent cognitive and neurological impairments. Members of the
      protein kinase C (PKC) family play a key role in the regulation of cellular
      functions in the nervous system. Alteration of PKC can be involved in the
      pathogenesis of neuronal disorders. This review details recent progress made in
      determining the roles played by PKC isoforms in developing hypothyroid rat brain.
      Evidence indicates that hippocampus down-regulation of PKCbeta and PKCgamma may
      be related to impaired learning and memory observed in perinatal hypothyroid
      rats. Enhanced PKCalpha activity in neonatal hypothyroid brain may bring about
      oxidative stress and cause brain damage. The activated pro-apoptotic PKCs
      including PKCdelta can cause extensive apoptosis in the hypothyroid rat brain. 

PMID- 24682729
TI  - Combined treatment with quercetin and imperatorin as a potent strategy for
      killing HeLa and Hep-2 cells.
AB  - The aim of the present study was to assess the effect of quercetin and
      imperatorin administered separately and in combination on apoptosis and autophagy
      induction in human cervical carcinoma HeLa cells and laryngeal carcinoma Hep-2
      cells cultured in vitro. Conducted MTT measurements proved that quercetin and
      imperatorin displayed a strong antiproliferative activity manifested in markedly
      reduction of HeLa and Hep-2 cells viability as a result of treatment with 50 MUM
      of each compound. Further cell staining assays revealed that concentration
      mentioned above generated the highest percentage of apoptotic cells especially in
      the case of application of both drugs for 48 h. Simultaneous quercetin and
      imperatorin administration induced apoptosis remarkably stronger than treatment
      with single drugs. Experiments at the molecular level confirmed these results
      accompanied with the decreased Hsp27 and Hsp72 expression and, in addition, with
      increased caspases activity. Autophagy was not observed and no significant
      changes in the expression of beclin-1 were noticed. Additionally, experiments
      were performed on the above-mentioned cell lines with blocked Hsp27 and Hsp72
      expression. In these cells, no significant changes in the sensitivity to
      apoptosis induction upon quercetin and imperatorin treatment were observed. The
      present study has provided evidence supporting the potential of the combination
      of quercetin and imperatorin drugs as a novel tool to be used in anticancer
      therapy. Our results have also demonstrated that blocking of the Hsp27 and Hsp72
      gene expression is not enough to sensitize cancer cells to programmed cell death
      induction in HeLa and Hep-2 cells. 

PMID- 24682730
TI  - Does toll-like receptor-3 (TLR-3) have any role in Indian AMD phenotype?
AB  - Age-related macular degeneration (AMD) is a devastating disease that results in
      irreversible central vision loss. TLRs signaling pathway has been found to play
      an important role in AMD pathogenesis as evidenced by several studies. The
      objective of the study was to determine the single nucleotide polymorphism (SNP)
      changes in TLR3 in North Indian AMD patients. We recruited 176 patients
      comprising 115 AMD patients and 61 controls. Real time PCR was used to evaluate
      the SNP changes at rs3775291 locus. Pearson's chi(2) test was used evaluate
      association between various groups. No significant association in genotype and
      allele frequency was found in AMD patients as compared to control. The results
      suggest that AMD pathology in North Indian AMD patients is not affected by TLR3
      signaling but it could be influenced by other genetic or environmental factors
      unique to North India.

PMID- 24682731
TI  - Unusual parapharyngeal extension of peritonsillar abscess to the masticator
      space: successfully drained by extraoral and intraoral endoscopic approaches.
AB  - OBJECTIVE: The object was to describe 2 novel cases of peritonsillar abscess
      showing peculiar extension to the masticator space. METHODS: The methods included
      clinical case records, including computed tomography and surgical approaches.
      RESULTS: Both patients we encountered were suffering from systematic diseases,
      with case 1 involving a 75-year-old man with diabetes mellitus and case 2
      involving a 90-year-old woman taking immunosuppressive medications. The abscesses
      were peritonsillar in origin, extending primarily to the parapharyngeal space,
      with unusual secondary extension to the masticator space. Extraoral drainage
      conducted in case 1 was useful for assessing the masticator space and surrounding
      spaces, but endoscopy-assisted intraoral drainage in case 2 was less invasive,
      obviating the need for identifying the facial nerve. CONCLUSIONS: It is important
      to bear in mind that patients suffering from systemic diseases may display
      unusual extension of deep head and neck infections, and enhanced computed
      tomography is a useful modality for evaluating such extensions.

PMID- 24682732
TI  - Improvement in sensorineural hearing loss during pregnancy.
AB  - OBJECTIVE: Hearing loss is known to occur in some pregnant women, but improvement
      in sensorineural thresholds has not been audiometrically characterized. Here, we
      describe a patient with a history of Meniere's disease and vestibular migraine
      who experienced temporary recovery of her hearing during pregnancy. METHODS:
      Audiograms were obtained from a 31-year-old female over the course of 2
      successive pregnancies. RESULTS: Audiograms revealed a substantial improvement in
      hearing by the third trimester during each pregnancy, with a rapid return to
      baseline thresholds after delivery. CONCLUSION: This case is unique in
      documenting improvements in hearing thresholds during pregnancy and substantiates
      the effects of hormonal changes on hearing thresholds in humans. It raises the
      intriguing possibility of hormonal therapy as a treatment for sensorineural
      hearing loss in specific clinical situations.

PMID- 24682733
TI  - Otologic manifestations of immunoglobulin G4-related disease.
AB  - OBJECTIVE: Immunoglobulin (Ig) G4-related disease is systemic, and it has been
      reported that patients with IgG4-related disease complain of symptoms involving
      numerous organs. However, there are few reports concerning the otologic
      manifestations of IgG4-related disease. The purpose of this study is to
      investigate the clinical features of the otologic manifestations in IgG4-related
      disease. METHODS: We recruited 39 consecutive patients diagnosed with IgG4
      related disease. Otologic symptoms, laboratory data, and audiogram findings were
      retrospectively examined. Mucosal tissues from the inferior turbinate were
      obtained from subjects before treatment. The serum IgG4 and eosinophil levels
      together with clinical features were analyzed. RESULTS: Five of the 39 cases had
      some otologic symptoms. Otitis media with effusion was present in 2 patients.
      Sensorineural hearing loss was also present in I patient. Eosinophilic otitis
      media was present in 2 patients with bilateral rhinosinusitis and bronchial
      asthma, and elevated serum eosinophil levels. Oral prednisolone was effective in
      the treatment of IgG4-related disease. CONCLUSION: We revealed a new clinical
      entity associated with the otologic manifestations of IgG4-related disease.

PMID- 24682734
TI  - EpimiR: a database of curated mutual regulation between miRNAs and epigenetic
      modifications.
AB  - As two kinds of important gene expression regulators, both epigenetic
      modification and microRNA (miRNA) can play significant roles in a wide range of
      human diseases. Recently, many studies have demonstrated that epigenetics and
      miRNA can affect each other in various ways. In this study, we established the
      EpimiR database, which collects 1974 regulations between 19 kinds of epigenetic
      modifications (such as DNA methylation, histone acetylation, H3K4me3, H3S10p) and
      617 miRNAs across seven species (including Homo sapiens, Mus musculus, Rattus
      norvegicus, Gallus gallus, Epstein-Barr virus, Canis familiaris and Arabidopsis
      thaliana) from >300 references in the literature. These regulations can be
      divided into two parts: miR2Epi (103 entries describing how miRNA regulates
      epigenetic modification) and Epi2miR (1871 entries describing how epigenetic
      modification affects miRNA). Each entry of EpimiR not only contains basic
      descriptions of the validated experiment (method, species, reference and so on)
      but also clearly illuminates the regulatory pathway between epigenetics and
      miRNA. As a supplement to the curated information, the EpimiR extends to gather
      predicted epigenetic features (such as predicted transcription start site,
      upstream CpG island) associated with miRNA for users to guide their future
      biological experiments. Finally, EpimiR offers download and submission pages.
      Thus, EpimiR provides a fairly comprehensive repository about the mutual
      regulation between epigenetic modifications and miRNAs, which will promote the
      research on the regulatory mechanism of epigenetics and miRNA. Database URL:
      http://bioinfo.hrbmu.edu.cn/EpimiR/. 

PMID- 24682735
TI  - The eGenVar data management system--cataloguing and sharing sensitive data and
      metadata for the life sciences.
AB  - Systematic data management and controlled data sharing aim at increasing
      reproducibility, reducing redundancy in work, and providing a way to efficiently
      locate complementing or contradicting information. One method of achieving this
      is collecting data in a central repository or in a location that is part of a
      federated system and providing interfaces to the data. However, certain data,
      such as data from biobanks or clinical studies, may, for legal and privacy
      reasons, often not be stored in public repositories. Instead, we describe a
      metadata cataloguing system and a software suite for reporting the presence of
      data from the life sciences domain. The system stores three types of metadata:
      file information, file provenance and data lineage, and content descriptions. Our
      software suite includes both graphical and command line interfaces that allow
      users to report and tag files with these different metadata types. Importantly,
      the files remain in their original locations with their existing access-control
      mechanisms in place, while our system provides descriptions of their contents and
      relationships. Our system and software suite thereby provide a common framework
      for cataloguing and sharing both public and private data. Database URL:
      http://bigr.medisin.ntnu.no/data/eGenVar/.

PMID- 24682736
TI  - Successful readministration of trastuzumab after severe immune reactions in two
      breast cancer patients.
AB  - Trastuzumab is a standard treatment in breast cancer overexpressing Her2
      oncogene. However, its administration carries the risk of severe immune adverse
      events which often lead to the discontinuation of trastuzumab. There is no clear
      guideline on how patients experiencing trastuzumab-related reaction should be
      rechallenged with the monoclonal antibody. Here, we present two case reports of
      patients who have presented severe anaphylactic reactions during trastuzumab
      infusion. Both of them have been successfully rechallenged in intensive care
      units with premedication, lower rate of infusion and vitals monitoring.
      Thereafter, trastuzumab could be continued without any serious adverse reaction.
      Given the positive impact of trastuzumab on patients' survival, treatment
      rechallenge should be carefully considered in patients who presented anaphylactic
      reactions.

PMID- 24682738
TI  - Expression of dopaminergic receptors on human CD4+ T lymphocytes: flow cytometric
      analysis of naive and memory subsets and relevance for the neuroimmunology of
      neurodegenerative disease.
AB  - Dopamine (DA) is a crucial transmitter in the neuroimmune network, where it
      contributes to the nervous system-immune system interplay as well as in the
      communication among immune cells. DA acts through five different dopaminergic
      receptors (DR) grouped into two families: the D1-like (D1 and D5) and the D2-like
      (D2, D3 and D4). By use of 5-color flow cytometric analysis, we examined the
      expression of DR on human CD4+ naive T lymphocytes (CD3+CD4+CD45RA+CCR7+),
      central memory (TCM, CD3+CD4+CD45RA-CCR7+) and effector memory T cells (TEM,
      CD3+CD4+CD45RA-CCR7-). In addition, in cultured CD4+ T cells we investigated the
      changes in DR expression induced by stimulation with antiCD3/antiCD28 antibodies.
      Results showed that CD4+ T cells always expressed all the five DR: D1-like DR
      were identified on average on 11.6-13.1 % and D2-like DR on 3.1-8.1 % of the
      cells. DR on CD4+ naive T cells, TCM, and TEM had distinct expression patterns:
      naive T cells expressed more D1-like than D2-like DR, which on the contrary were
      increased in TCM and TEM cells. In cultured CD4+ T cells stimulation with anti
      CD3/anti-CD28 antibodies increased the expression of D1-like DR by 71-84 % and of
      D2-like DR by 55-97 %. The frequency of DR was higher in apoptotic cells in
      comparison to viable cells, however stimulation increased all DR on viable cells,
      without affecting their expression on apoptotic cells. The present results
      contribute to unravel the complexity of dopaminergic pathways in human CD4+ T
      lymphocytes, suggesting their involvement in memory functions as well as in
      apoptotic processes. In view of the role of CD4+ memory T cells in
      neuroinflammation and neurodegeneration during Parkinson's disease, the relevance
      of these findings must be assessed in the clinical setting.

PMID- 24682739
TI  - Probing for improved potency and in vivo bioavailability of excitatory amino acid
      transporter subtype 1 inhibitors UCPH-101 and UCPH-102: design, synthesis and
      pharmacological evaluation of substituted 7-biphenyl analogs.
AB  - Uptake of the major excitatory neurotransmitter in the CNS, (S)-glutamate, is
      mediated by a family of excitatory amino acid transporters (EAAT). Previously we
      have explored the structure-activity relationship (SAR) of a series of EAAT1
      selective inhibitors, leading to the development of the potent inhibitors UCPH
      101 and UCPH-102. In the present study, we set out to improve the solubility
      properties of these EAAT1 inhibitors with the objective to develop analogs more
      suited as pharmacological tools for in vivo studies of EAAT1 in terms of their
      bioavailability. A total of 23 novel UCPH-101/102 analogs were designed,
      synthesized and characterized pharmacologically at EAAT1-3 in a [(3)H]-D
      aspartate uptake assay. Most notably, the potent EAAT1 inhibition displayed of
      UCPH-101 and UCPH-102 was retained in analog 1d in which the napht-1-yl group in
      the 7-position of UCPH-102 has been replaced by an o-biphenyl moiety. In
      contrast, EAAT1 activity was dramatically compromised in analogs 1e and 1f
      comprising m- and p-biphenyl groups as 7-substituents, respectively. Analog 1d
      displayed low bioavailability after oral administration in rats, and this problem
      was addressed by the synthesis of a series of analogs with different chloro,
      fluoro, methoxy, triflouromethyl and carboxy substitution patterns at the o
      biphenyl group of 1d (1h-1s) and m- and p-pyridine analogs of 1d (1t and 1v).
      Unfortunately, all of the modifications resulted in substantial decreased EAAT1
      inhibitory activity, which supports the notion of a very lipophilic binding
      pocket in EAAT1 for the aromatic 7-substituent in these ligands. In conclusion,
      while we have not succeeded in developing UCPH-101/102 analogs possessing
      improved bioavailability properties, this study does offer interesting SAR
      information about this inhibitor class, and analog 1d seems to be an interesting
      lead for future SAR studies with focus on the development of more potent EAAT1
      inhibitors.

PMID- 24682740
TI  - Detection of serum p53 antibodies from Chinese patients with papillary thyroid
      carcinoma using phage-SP-ELISA: correlation with clinical parameters.
AB  - The goal of the present study was to investigate whether p53 antibodies (Abs)
      could be a relevant marker for papillary thyroid carcinoma (PTC). Three types of
      enzyme-linked immunosorbent assay (ELISA) methods were developed for the
      detection of p53 Abs, including p53-ELISA, phage-SS-ELISA, and phage-SP-ELISA. A
      total of 304 patients, including 117 cases with thyroid adenoma and 187 PTC
      patients, were enrolled in this study. Expression of p53 protein and mutation in
      BRAF gene were evaluated in paraffin-embedded tissue from 44 patients with PTC,
      in order to elucidate their correlations with the presence of p53 Abs. Compared
      with p53-ELISA and phage-SS-ELISA, phage-SP-ELISA presented the highest detection
      efficiency of p53 Abs in patients with PTC, and a combination of these three
      ELISA systems could make the detection of p53 Abs more sensitive than using each
      of the individual ELISA methods. Furthermore, p53 Abs was positively associated
      with clinical stage (P = 0.044), node metastasis (P = 0.010), and p53 protein
      accumulation (P = 0.019). These results indicate that serum p53 Abs could be a
      useful marker for PTC.

PMID- 24682741
TI  - Precision of the PRECICE internal bone lengthening nail.
AB  - BACKGROUND: Previous designs of internal bone lengthening devices have been
      fraught with imprecise distraction, resulting in nerve injuries, joint
      contractures, nonunions, and other complications. Recently, a magnet-operated
      PRECICE nail (Ellipse Technologies, Inc, Irvine, CA, USA) was approved by the
      FDA; however, its clinical efficacy is unknown. QUESTIONS/PURPOSES: We evaluated
      this nail in terms of (1) accuracy and precision of distraction, (2) effects on
      bone alignment, (3) effects on adjacent-joint ROM, and (4) frequency of implant
      related and non-implant-related complications. METHODS: We reviewed medical and
      radiographic records of 24 patients who underwent femoral and/or tibial
      lengthening procedures using the PRECICE nail from August 2012 to July 2013 for
      conditions of varied etiology, the most common being congenital limb length
      discrepancy, posttraumatic growth arrest, and fracture malunion. This group
      represented 29% of patients (24 of 82) who underwent a limb lengthening procedure
      for a similar diagnosis during the review period. At each postoperative visit,
      the accuracy and precision of distraction, bone alignment, joint ROM, and any
      complications were recorded by the senior surgeon (SRR). Accuracy reflected how
      close the measured lengthening was to the prescribed distraction at each
      postoperative visit, while precision reflected how close the repeated
      measurements were to each other over the course of total lengthening period. No
      patients were lost to followup. Minimum followup from surgery was 3 weeks (mean,
      14 weeks; range, 3-29 weeks). RESULTS: Mean total lengthening was 35 mm (range,
      14-65 mm), with an accuracy of 96% and precision of 86%. All patients achieved
      target lengthening with minimal unintentional effects on bone alignment. The knee
      and ankle ROM were minimally affected. Of the complications requiring return to
      the operating room for an additional surgical procedure, there was one (4%)
      implant failure caused by a nonfunctional distraction mechanism and six (24%) non
      implant-related complications, including premature consolidation in one patient
      (4%), delayed bone healing in two (8%), delayed equinus contracture in two (8%),
      and toe clawing in one (4%). CONCLUSIONS: We conclude that this internal
      lengthening nail is a valid option to achieve accurate and precise limb
      lengthening to treat a variety of conditions with limb shortening or length
      discrepancy. Randomized, larger-sample, long-term studies are required to further
      confirm clinical efficacy of these devices, monitor for any late failures and
      complications, and compare with other internal lengthening devices with different
      mechanisms of operation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24682742
TI  - A study of the rotational barriers for some organic compounds using the G3 and
      G3CEP theories.
AB  - The G3, G3CEP, MP4, MP4CEP, QCISD(T), and QCISD(T)CEP methods were applied to
      study 43 internal rotational barriers of different molecules. The calculated G3
      and G3CEP barriers were accurate with respect to those obtained experimentally,
      typically showing deviations of <0.50 kcal mol-1. The results for the MP4CEP,
      MP4, QCISD(T), and QCISD(T)CEP calculations were less accurate, and larger
      deviations of approximately +/-1 kcal mol-1 were observed. The accuracy of G3CEP
      was comparable to that of G3, but a reduction in CPU time of between 5 and 35 %
      was observed when the dependence of the pseudopotentials on the size of the
      molecule and atom type was taken into account. The behaviors of the energy
      components show that these corrections depend on the molecular environment and
      whether the calculations are performed with all electrons or pseudopotentials.
      Usually, the predominance of a specific effect follows a distinct pattern when
      the G3 and G3CEP results are compared. For the G3 calculations, the most
      important component of the corrected MP4/6-31G(d) rotational energy is
      DeltaE(2df,p). Among the 43 molecules, 29 were dependent on polarization effects,
      DeltaE(2df,p); 19 were dependent on diffuse functions, DeltaE +; and 13 depended
      on the effects of more elaborate basis functions (DeltaE(G3large)). Similar
      behavior was observed for the G3CEP calculations: polarization effects were more
      important for 25 molecules, followed closely by the effect of diffuse functions
      for 23 molecules, and finally the effect of large basis sets (19 molecules).
      DeltaE(QCI) correction seldom resulted in significant effects on the G3 and G3CEP
      calculations.

PMID- 24682743
TI  - Changes to stage 1 meaningful use in 2014: impact on radiologists.
AB  - The goal of this work is to provide radiologists an update regarding changes to
      stage 1 of meaningful use in 2014. These changes were promulgated in the final
      rulemaking released by the Centers for Medicare and Medicaid Services and the
      Office of the National Coordinator for Health Information Technology in September
      2012. Under the new rules, radiologists are exempt from meaningful use penalties
      provided that they are listed as radiologists under the Provider Enrollment,
      Chain and Ownership System (PECOS). A major caveat is that this exemption can be
      removed at any time. Additional concerns are discussed in the main text.
      Additional changes discussed include software editions independent of meaningful
      use stage (i.e., 2011 edition versus 2014 edition), changes to the definition of
      certified electronic health record technology (CEHRT), and changes to specific
      measures and exemptions to those measures. The new changes regarding stage 1 add
      complexity to an already complex program, but overall make achieving meaningful
      use a win-win situation for radiologists. There are no penalties for failure and
      incentive payments for success. The cost of upgrading to CEHRT may be much less
      than the incentive payments, adding a potential new source of revenue. Additional
      benefits may be realized if the radiology department can build upon a modern
      electronic health record to improve their practice and billing patterns.
      Meaningful use and electronic health records represent an important evolutionary
      step in US healthcare, and it is imperative that radiologists are active
      participants in the process. 

PMID- 24682745
TI  - Risk of second benign brain tumors among cancer survivors in the surveillance,
      epidemiology, and end results program.
AB  - PURPOSE: To assess risk of developing a second benign brain tumor in a nationwide
      population of cancer survivors. METHODS: We evaluated the risk of developing
      second benign brain tumors among 2,038,074 1-year minimum cancer survivors
      compared to expected risk in the general population between 1973 and 2007 in nine
      population-based cancer registries in the NCI's surveillance, epidemiology, and
      end results program. Excess risk was estimated using standardized incidence
      ratios (SIRs) for all second benign brain tumors and specifically for second
      meningiomas and acoustic neuromas diagnosed during 2004-2008. RESULTS: 1,025
      patients were diagnosed with a second primary benign brain tumor, of which second
      meningiomas composed the majority (n = 745). Statistically significant increases
      in risk of developing a second meningioma compared to the general population were
      observed following first cancers of the brain [SIR = 19.82; 95 % confidence
      interval (CI) 13.88-27.44], other central nervous system (CNS) (SIR = 9.54; CI
      3.10-22.27), thyroid (SIR = 2.05; CI 1.47-2.79), prostate (SIR = 1.21; CI 1.02
      1.43), and acute lymphocytic leukemia (ALL) (SIR = 42.4; CI 23.18-71.13).
      Statistically significant decreases in risk were observed following first cancers
      of the uterine corpus (SIR = 0.63; CI 0.42-0.91) and colon (SIR = 0.56; CI 0.37
      0.82). Differences in risk between patients initially treated with radiotherapy
      versus non-irradiated patients were statistically significant for second
      meningioma after primary cancers of the brain (p Het < 0.001) and ALL (p Het =
      0.02). No statistically significant increased risks were detected for second
      acoustic neuromas (n = 114) following any first primary tumor. CONCLUSIONS: Risk
      of second benign brain tumors, particularly meningioma, is increased following
      first primary cancers of the brain/CNS, thyroid, prostate, and ALL. Radiation
      exposure likely contributes to these excess risks.

PMID- 24682746
TI  - Dietary patterns and colorectal cancer risk in Japan: the Ohsaki Cohort Study.
AB  - PURPOSE: To evaluate dietary patterns in relation to colorectal cancer risk in
      Japanese. METHODS: We prospectively assessed the association between dietary
      patterns among the Japanese and the risk of colorectal cancer. Dietary
      information was collected from 44,097 Japanese men and women aged 40-79 years
      without a history of cancer at the baseline in 1994. RESULTS: During 11 years of
      follow-up, we documented 854 cases of colorectal cancer, which included 554 cases
      of colon cancer and 323 cases of rectal cancer. Factor analysis (principal
      component analysis) based on a validated food frequency questionnaire identified
      three dietary patterns: (1) a Japanese dietary pattern, (2) an "animal food"
      dietary pattern, and (3) a high-dairy, high-fruit-and-vegetable, low-alcohol
      (DFA) dietary pattern. After adjustment for potential confounders, the DFA
      pattern was inversely associated with the risk of colorectal cancer (hazard ratio
      of the highest quartile vs the lowest, 0.76; 95 % confidence interval 0.60-0.97;
      p for trend = 0.02). When colon and rectal cancers were separated, the inverse
      association between the DFA pattern and cancer risk was observed for rectal
      cancer (p for trend = 0.003), but not for colon cancer (p for trend = 0.43). No
      apparent association was observed for either the Japanese dietary pattern or the
      "animal food" dietary pattern. CONCLUSIONS: The DFA dietary pattern was found to
      be inversely associated with the risk of colorectal cancer. This association was
      observed for rectal cancer, but not for colon cancer.

PMID- 24682748
TI  - Exploratory structural equation modeling of personality data.
AB  - The current article compares the use of exploratory structural equation modeling
      (ESEM) as an alternative to confirmatory factor analytic (CFA) models in
      personality research. We compare model fit, factor distinctiveness, and criterion
      associations of factors derived from ESEM and CFA models. In Sample 1 (n = 336)
      participants completed the NEO-FFI, the Trait Emotional Intelligence
      Questionnaire-Short Form, and the Creative Domains Questionnaire. In Sample 2 (n
      = 425) participants completed the Big Five Inventory and the depression and
      anxiety scales of the General Health Questionnaire. ESEM models provided better
      fit than CFA models, but ESEM solutions did not uniformly meet cutoff criteria
      for model fit. Factor scores derived from ESEM and CFA models correlated highly
      (.91 to .99), suggesting the additional factor loadings within the ESEM model add
      little in defining latent factor content. Lastly, criterion associations of each
      personality factor in CFA and ESEM models were near identical in both
      inventories. We provide an example of how ESEM and CFA might be used together in
      improving personality assessment.

PMID- 24682747
TI  - The HSP90 inhibitor ganetespib has chemosensitizer and radiosensitizer activity
      in colorectal cancer.
AB  - The integration of targeted agents to standard cytotoxic regimens has improved
      outcomes for patients with colorectal cancer (CRC) over recent years; however
      this malignancy remains the second leading cause of cancer mortality in
      industrialized countries. Small molecule inhibitors of heat shock protein 90
      (HSP90) are one of the most actively pursued classes of compounds for the
      development of new cancer therapies. Here we evaluated the activity of
      ganetespib, a second-generation HSP90 inhibitor, in models of CRC. Ganetespib
      reduced cell viability in a panel of CRC cell lines in vitro with low nanomolar
      potency. Mechanistically, drug treatment exerted concomitant effects on multiple
      oncogenic signaling pathways, cell cycle regulation, and DNA damage repair
      capacity to promote apoptosis. Combinations of ganetespib and low-dose ionizing
      radiation enhanced the radiosensitivity of HCT 116 cells and resulted in superior
      cytotoxic activity over either treatment alone. In vivo, the single-agent
      activity of ganetespib was relatively modest, suppressing HCT 116 xenograft tumor
      growth by approximately half. However, ganetespib significantly potentiated the
      antitumor efficacy of the 5-Fluorouracil (5-FU) prodrug capecitabine in HCT 116
      xenografts, causing tumor regressions in a model that is intrinsically resistant
      to fluoropyrimidine therapy. This demonstration of combinatorial benefit afforded
      by an HSP90 inhibitor to a standard CRC adjuvant regimen provides an attractive
      new framework for the potential application of ganetespib as an investigational
      agent in this disease. 

PMID- 24682749
TI  - Effects of A379V variant of the Lp-PLA 2 gene on Lp-PLA 2 activity and markers of
      oxidative stress and endothelial function in Koreans.
AB  - A379V variant in the lipoprotein-associated phospholipase A2 (Lp-PLA 2) gene is
      known to be functional, but there are contradicting data concerning the A379V
      polymorphism, Lp-PLA2 activity and cardiovascular disease risk. We determined the
      interplay between A379V SNP, Lp-PLA2 activity, and markers of oxidative stress
      and endothelial function with and without the effect of V279F variant. 3,220
      unrelated and healthy Koreans (40-79 years) were genotyped for the Lp-PLA 2
      polymorphism (A379V and V279F). Lp-PLA2 activity and markers of oxidative stress
      and endothelial function were measured. Lp-PLA2 activity was 3.9% higher in A/V
      subjects (n = 821) and 7.8% in V/V (n = 79) than in those with A/A (n = 2,320).
      Urinary levels of 8-epi-PGF2alpha were significantly lower in subjects with the
      A/V or the V/V genotype than in those with the A/A genotype (A/A; 1,426 +/- 14,
      A/V; 1,371 +/- 26, V/V; 1,199 +/- 58 pg/mg creatinine, P = 0.003). Subjects with
      the 379 V/V genotype had lower serum concentrations of sICAM-1 and p-selectin
      compared to those with the A/A or the A/V genotype. When subjects were further
      stratified into subgroups based on the combination of A379V and V279F genotypes,
      there was no significant association between A379V genotypes and Lp-PLA2
      activities in the 279 V/V group. However, the associations of the A379V SNP with
      levels of 8-epi-PGF2alpha, sICAM-1, and p-selectin remained in the subset
      analysis based on the V279F genotypes. This study showed a reduction in oxidative
      stress in subjects carrying 379V allele and the recessive effect of the A379V on
      the endothelial function. It is likely that the A379V polymorphism has a
      qualitative effect, probably by disrupting the affinity of Lp-PLA2 for platelet
      activating factor substrate, towards a more anti-oxidative or anti-atherogenic
      form.

PMID- 24682750
TI  - Chromosomal polymorphism in two species of Hypancistrus (Siluriformes:
      Loricariidae): an integrative approach for understanding their biodiversity.
AB  - Structural chromosome changes are widely described in different vertebrate groups
      and generate genetic, phenotypic and behavioral diversity. During the evolution
      of loricariids, several rearrangements (fissions, fusions, inversions) seem to
      have occurred. Hypancistrus, tribe Ancistrini, are highly demanded for
      fishkeeping around the world. In this tribe, the diploid chromosome number 2n =
      52 is considered a synapomorphy, and paracentric-type inversions appear to be
      involved in the chromosomal evolution of the tribe. The present study
      investigated the karyotypes of H. zebra and H. cf. debilittera using cytogenetic,
      classical and molecular tools, as well as DNA barcoding. Data reveal that,
      although diploid number in both species corroborates the proposed synapomorphy
      for the tribe, there is a complex karyotype dynamics, reflected in the intense
      chromosomal polymorphism, resulting from rearrangements involving ribosomal
      regions (5S and 18S rDNA), which are suggested to be paracentric inversions.
      Besides, DNA barcode confirms reciprocal monophyletism between the species,
      validating the existence of two species, only. This scenario, coupled with
      genomic instability caused by exogenous sequences such as Rex-3 retrotransposons
      and the species' sedentary lifestyle, which helps the fast polymorphism fixation,
      may reflect different phenotypic color patterns in natural populations, as
      observed in H. cf. debilittera.

PMID- 24682751
TI  - Angiotensin II inhibits iron uptake and release in cultured neurons.
AB  - Based on the well-confirmed roles of angiotensin II (ANGII) in iron transport of
      peripheral organs and cells, the causative link of excess brain iron with and the
      involvement of ANGII in neurodegenerative disorders, we speculated that ANGII
      might also have an effect on expression of iron transport proteins in the brain.
      In the present study, we investigated effects of ANGII on iron uptake and release
      using the radio-isotope methods as well as expression of cell iron transport
      proteins by Western blot analysis in cultured neurons. Our findings demonstrated
      for the first time that ANGII significantly reduced transferrin-bound iron and
      non-transferrin bound iron uptake and iron release as well as expression of two
      major iron uptake proteins transferrin receptor 1 and divalent metal transporter
      1 and the key iron exporter ferroportin 1 in cultured neurons. The findings
      suggested that endogenous ANGII might have a physiological significance in brain
      iron metabolism. 

PMID- 24682752
TI  - Sphingosine kinase-1 protects differentiated N2a cells against beta-amyloid25-35
      induced neurotoxicity via the mitochondrial pathway.
AB  - Although the etiology of Alzheimer's disease (AD) is not fully understood,
      multiple lines of evidence suggests the importance of amyloid-beta (Abeta) in the
      initiation/progression of the disease. Abeta has been shown to induce neuronal
      apoptosis via the sphingomyelin/ceramide pathway. This study was designed to
      elucidate whether the sphingosine kinase-1 (SPK1), a critical regulator of the
      ceramide/sphingosine 1-phosphate rheostat, plays a pivotal role in the regulation
      of death and survival of differentiated neuro-2a cells in response to beta
      amyloid peptide fragment 25-35 (Abeta25-35). These results show that the
      expression of SPK1 was markedly decreased in Abeta25-35-induced neurotoxicity, as
      evidenced by the decreased cell viability and the increased apoptotic rate.
      Overexpression of SPK1 significantly attenuated Abeta25-35-induced neurotoxicity,
      whereas silencing the expression of SPK1 exacerbated it. Moreover, overexpression
      of SPK1 can significantly attenuate Abeta25-35-induced upregulation of Bax and
      rehabilitate the level of Bcl-2; concomitantly, it can ameliorate mitochondrial
      ultrastructure. These studies demonstrate that overexpression of SPK1 may
      moderate Abeta25-35-induced neurotoxicity by regulating the Bcl-2/Bax ratio and
      improving mitochondrial ultrastructure. Based on these findings, SPK1 is a
      potential therapeutic target for AD. 

PMID- 24682754
TI  - On the discovery and development of pimavanserin: a novel drug candidate for
      Parkinson's psychosis.
AB  - Parkinson's disease psychosis (PDP) is a condition that may develop in up to 60 %
      of Parkinson's patients, and is a major reason for nursing home placement for
      those affected. There are no FDA approved drugs for PDP but low doses of atypical
      anti-psychotic drugs (APDs) are commonly prescribed off-label. Only low-dose
      clozapine has shown efficacy in randomized controlled trials, but all APDs have
      black box warnings related to the increased mortality and morbidity when used in
      elderly demented patients. Using molecular pharmacological profiling of a large
      collection of marketed drugs, we discovered that potent inverse agonist activity
      against 5-HT2A serotonin receptors was a common feature of atypical APDs,
      especially the atypical APDs used to treat PDP. Since low-dose clozapine therapy
      selectively blocks this receptor, it was hypothesized that a highly selective 5
      HT2A receptor inverse agonist might provide good symptom control in patients
      suffering from PDP, with a greatly improved safety and tolerability profile. A
      high throughput screening and subsequent chemical lead optimization campaign to
      develop potent, selective 5-HT2A receptor inverse agonists was launched,
      eventually resulting in the discovery of pimavanserin. Pimavanserin displays
      nanomolar potency as a 5-HT2A receptor inverse agonist, selectivity for 5-HT2A
      over 5-HT2C receptors, and no meaningful activity at any other G-protein coupled
      receptor. It demonstrated robust activity in preclinical models of schizophrenia
      and PDP, and did not worsen motoric symptoms, in contrast to the APDs tested. In
      a Phase III clinical trial, pimavanserin showed highly significant benefits in
      the primary endpoint, the scale for assessment of positive symptoms-PD, a scale
      adapted for use in PDP. In addition, improvements in all other efficacy
      endpoints, including physician's clinical global impression, caregiver burden,
      night-time sleep quality and daytime wakefulness, were seen. Pimavanserin
      demonstrated good safety and tolerability and did not worsen motoric symptoms as
      assessed by the unified Parkinson's disease rating scale parts II and III. An
      open-label extension study has further demonstrated that pimavanserin is safe and
      well-tolerated with long-term use. Pimavanserin may therefore offer a viable
      treatment option for patients suffering from PDP.

PMID- 24682753
TI  - Hyperbaric oxygen therapy ameliorates local brain metabolism, brain edema and
      inflammatory response in a blast-induced traumatic brain injury model in rabbits.
AB  - Many studies suggest that hyperbaric oxygen therapy (HBOT) can provide some
      clinically curative effects on blast-induced traumatic brain injury (bTBI). The
      specific mechanism by which this occurs still remains unknown, and no
      standardized time or course of hyperbaric oxygen treatment is currently used. In
      this study, bTBI was produced by paper detonators equivalent to 600 mg of TNT
      exploding at 6.5 cm vertical to the rabbit's head. HBO (100% O2 at 2.0 absolute
      atmospheres) was used once, 12 h after injury. Magnetic resonance spectroscopy
      was performed to investigate the impact of HBOT on the metabolism of local
      injured nerves in brain tissue. We also examined blood-brain barrier (BBB)
      integrity, brain water content, apoptotic factors, and some inflammatory
      mediators. Our results demonstrate that hyperbaric oxygen could confer
      neuroprotection and improve prognosis after explosive injury by promoting the
      metabolism of local neurons, inhibiting brain edema, protecting BBB integrity,
      decreasing cell apoptosis, and inhibiting the inflammatory response. Furthermore,
      timely intervention within 1 week after injury might be more conducive to
      improving the prognosis of patients with bTBI.

PMID- 24682755
TI  - Prenatal restraint stress is associated with demethylation of corticotrophin
      releasing hormone (CRH) promoter and enhances CRH transcriptional responses to
      stress in adolescent rats.
AB  - Maternal stress can disturb normal fetal neurodevelopmental progress, and lead to
      negative behavioral and neuroendocrine consequences for the offspring. These
      effects may be related to alterations in the hypothalamic-pituitary-adrenal (HPA)
      axis. Early life events disrupting the function of the HPA axis may be associated
      with epigenetic modification. This study investigated the effect of maternal
      stress on the methylation rate of the corticotrophin-releasing hormone (CRH)
      promoter and HPA axis response to acute stress in the adolescent offspring of
      Sprague-Dawley rats. Pregnant dams were randomly assigned to two groups:
      restraint stress group and normal control group. Adolescent male and female
      offspring were used from each group. The results showed that prenatal stress is
      associated with the demethylation of the CRH promoter, and leads to anxiety-like
      behaviors in adolescent life stages, as well as hyper-responsiveness of the HPA
      axis. Together, these results imply that prenatal stress alters the normal HPA
      function, which may be via the epigenetic mechanism. 

PMID- 24682757
TI  - Aldosterone-secreting adrenal cortical carcinoma. A case report and review of the
      literature.
AB  - Adrenal cortical carcinomas (ACC) are rare, typically aggressive malignant
      neoplasms with a reported incidence of 1-2 cases per 1 million population and
      account for 0.05-0.2 % of all malignancies. The majority of these tumors are
      functional with approximately 60 % of patients experiencing endocrine
      symptomatology typically characterized by Cushing's syndrome (40 %) or a mixed
      hormonal picture of Cushing syndrome seen in association with virilization.
      Rarely, patients present with a pure hormonal syndrome of feminization or
      hyperaldosteronism, 6 and 2.5 %, respectively. We report a case of a 76-year-old
      woman presenting with recently diagnosed hypertension secondary to primary
      hyperaldosteronism. The patient underwent laparoscopic converted to an open
      adrenalectomy and a diagnosis of adrenocortical carcinoma (aldosteronoma
      clinical) was rendered. This case and review of the literature highlight that
      while rare, aldosterone-secreting adrenal cortical carcinomas may occur. In this
      case report, we discuss the clinical presentation, pathologic findings, and
      review the literature for adrenal cortical carcinomas and aldosterone-secreting
      adrenal cortical carcinomas.

PMID- 24682756
TI  - Identification of bioactivating enzymes involved in the hydrolysis of laninamivir
      octanoate, a long-acting neuraminidase inhibitor, in human pulmonary tissue.
AB  - Laninamivir octanoate (LO) is an octanoyl ester prodrug of the neuraminidase
      inhibitor laninamivir. After inhaled administration, LO exhibits clinical
      efficacy for both treatment and prophylaxis of influenza virus infection,
      resulting from hydrolytic bioactivation into its pharmacologically active
      metabolite laninamivir in the pulmonary tissue. In this study, we focused on the
      identification of LO-hydrolyzing enzymes from human pulmonary tissue extract
      using proteomic correlation profiling-a technology integration of traditional
      biochemistry and proteomics. In a single elution step by gel-filtration
      chromatography, LO-hydrolyzing activity was separated into two distinct peaks,
      designated as peak I and peak II. By mass spectrometry, 1160 and 1003 proteins
      were identified and quantitated for peak I and peak II, respectively, and enzyme
      candidates were ranked based on the correlation coefficient between the enzyme
      activity and the proteomic profiles. Among proteins with a high correlation
      value, S-formylglutathione hydrolase (esterase D; ESD) and acyl-protein
      thioesterase 1 (APT1) were selected as the most likely candidates for peak I and
      peak II, respectively, which was confirmed by LO-hydrolyzing activity of
      recombinant proteins. In the case of peak II, LO-hydrolyzing activity was
      completely inhibited by treatment with a specific APT1 inhibitor, palmostatin B.
      Moreover, immunohistochemical analysis revealed that both enzymes were mainly
      localized in the pulmonary epithelia, a primary site of influenza virus
      infection. These findings demonstrate that ESD and APT1 are key enzymes
      responsible for the bioactivation of LO in human pulmonary tissue. 

PMID- 24682758
TI  - The bright and fascinating world of the neuroendocrine cells.

PMID- 24682759
TI  - Strategies in organic synthesis for condensed arenes, coronene, and graphene.
AB  - Graphene-type structures are without doubt one of the most exciting carbon-based
      materials known. Although graphene is mostly prepared by physical methods (CVD,
      exfoliation), organic synthesis represents a powerful alternative to access
      graphene-type structures in a selective and reproducible manner. Although
      graphene has been hyped as a "new" material, the resemblance to polycyclic
      aromatic hydrocarbons (PAHs) offers a long history in organic chemistry on which
      all new endeavors are built. In this review we demonstrate the state-of-the-art
      of organic synthetic strategies for the preparation of graphene-type structures
      on selected examples.

PMID- 24682760
TI  - Modeling materials and processes in dye-sensitized solar cells: understanding the
      mechanism, improving the efficiency.
AB  - We present a review of recent first-principles computational modeling studies on
      dye-sensitized solar cells (DSCs), focusing on the materials and processes
      modeling aspects which are key to the functioning of this promising class of
      photovoltaic devices. Crucial to the DSCs functioning is the photoinduced charge
      separation occurring at the heterointerface(s) between a dye-sensitized
      nanocrystalline, mesoporous metal oxide electrode and a redox shuttle.
      Theoretical and computational modeling of isolated cell components (e.g., dye,
      semiconductor nanoparticles, redox shuttle, etc...) as well as of combined
      dye/semiconductor/redox shuttle systems can successfully assist the experimental
      research by providing basic design rules of new sensitizers and a deeper
      comprehension of the fundamental chemical and physical processes governing the
      cell functioning and its performances. A computational approach to DSCs modeling
      can essentially be cast into a stepwise problem, whereby one first needs to
      simulate accurately the individual DSCs components to move to relevant pair (or
      higher order) interactions characterizing the device functioning. This
      information can contribute to enhancing further the target DSCs characteristics,
      such as temporal stability and optimization of device components. After
      presenting selected results for isolated dyes, including the computational design
      of new dyes, and model semiconductors, including realistic nanostructure models,
      we focus in the remainder of this review on the interaction between dye
      sensitizers and semiconductor oxides, covering organic as well as metallorganic
      dyes. 

PMID- 24682761
TI  - A theoretical and experimental chemist's joint view on hydrogen bonding in ionic
      liquids and their binary mixtures.
AB  - A combined experimental and theoretical approach including quantum chemistry
      tools and computational simulation techniques can provide a holistic description
      of the nature of the interactions present in ionic liquid media. The nature of
      hydrogen bonding in ionic liquids is an especially intriguing aspect, and it is
      affected by all types of interactions occurring in this media. Overall, these
      interactions represent a delicate balance of forces that influence the structure
      and dynamics, and hence the properties of ionic liquids. An understanding of the
      fundamental principles can be achieved only by a combination of computations and
      experimental work. In this contribution we show recent results shedding light on
      the nature of hydrogen bonding, for certain cases the formation of a three
      dimensional network of hydrogen bonding, and its dynamics by comparing 1-ethyl-3
      methylimidazolium based acetate, chloride and thiocyanate ionic liquids.A
      particularly interesting case to study hydrogen bonding and other interactions is
      the investigation of binary mixtures of ionic liquids of the type
      [cation1][anion1]/[cation1][anion2]. In these mixtures, competing interactions
      are to be expected. We present both a thorough property meta-analysis of the
      literature and new data covering a wide range of anions, i.e., mixtures of 1
      ethyl-3-methylimidazolium acetate with either trifluoroacetate,
      tetrafluoroborate, methanesulfonate, or bis(trifluoromethanesulfonyl)imide. In
      most cases, ideal mixing behavior is found, a surprising result considering the
      multitude of interactions present. However, ideal mixing behavior allows for the
      prediction of properties such as density, refractive index, surface tension, and,
      in most cases, viscosity as function of molar composition. Furthermore, we show
      that the prediction of properties such as the density of binary ionic liquid
      mixtures is possible by making use of group contribution methods which were
      originally developed for less complex non-ionic molecules. Notwithstanding this
      ideal mixing behavior, several exciting applications are discussed where
      preferential solvation via hydrogen bonding gives rise to non-additive effects
      leading to performance improvements. The assessment of the excess properties and
      (1)H NMR spectroscopic studies provide information on these structural changes
      and preferential interactions occurring in binary mixtures of ionic liquid, that
      clearly support the conclusions drawn from the computational studies. 

PMID- 24682764
TI  - On the decellularization of fresh or frozen human umbilical arteries:
      implications for small-diameter tissue engineered vascular grafts.
AB  - Most tissues, including those to be decellularized for tissue engineering
      applications, are frozen for long term preservation. Such conventional
      cryopreservation has been shown to alter the structure and mechanical properties
      of tissues. Little is known, however, how freezing affects decellularization of
      tissues. The purpose of this study was two-fold: to examine the effects of
      freezing on decellularization of human umbilical arteries (HUAs), which represent
      a potential scaffolding material for small-diameter tissue-engineered vascular
      grafts, and to examine how decellularization affects the mechanical properties of
      frozen HUAs. Among many decellularization methods, hypotonic sodium dodecyl
      sulfate solution was selected as the decellularizing agent and tested on fresh
      HUAs to optimize decellularization conditions. The efficiency of
      decellularization was evaluated by DNA assay and histology every 12 up to 48 h.
      The optimized decellularization protocol was then performed on frozen HUAs. The
      stiffness, burst pressure, and suture retention strength of fresh HUAs and frozen
      HUAs before and after decellularization were also examined. It appeared that
      freezing decreased the efficiency of decellularization, which may be attributed
      to the condensed extracellular matrix caused by freezing. While the stiffness of
      fresh HUAs did not change significantly after decellularization,
      decellularization reduced the compliance of frozen HUAs. Interestingly, the
      stiffness of decellularized frozen HUAs was similar to that of decellularized
      fresh HUAs. Although little difference in stiffness was observed, we suggest
      avoiding freezing if more efficient and complete decellularization is desired. 

PMID- 24682763
TI  - Current status of oral cancer treatment strategies: surgical treatments for oral
      squamous cell carcinoma.
AB  - The primary treatment modality of oral cancer is generally determined according
      to the stage of the disease, with surgical treatment remaining the mainstay of
      multimodal treatment. When selecting the treatment, many factors are taken into
      consideration, and the treatment should be tailored individually to the patient's
      needs and consider the quality of life as well as the survival of the patient.
      Early-stage disease is primarily managed with surgery or brachytherapy without
      functional morbidity, whereas for advanced-stage disease multidisciplinary
      treatment is recommended, not only for enhanced survival but also for improved
      quality of life. After resection of large primary tumors, reconstructive surgery
      is required. Free tissue transfer currently represents one of the most popular
      and reliable techniques for oral reconstruction. For cN0 neck, elective neck
      dissection is recommended when the risk of occult metastases is >20 %, when the
      neck is entered either for resection of the primary tumor or for reconstruction,
      or when the patient is unlikely to return for a close follow-up. Sentinel node
      biopsy is performed investigationally. Modified radical neck dissection is the
      gold standard for cN+ neck. For patients with multiple node metastases or
      extracapsular spread, postoperative radiotherapy or chemoradiotherapy is
      recommended, with the lymph nodes situated outside the confines of the radical
      neck dissection, such as the lingual and retropharyngeal nodes, receiving
      considerable attention. Targeted therapy for oral cancer is still a relatively
      new concept, and more studies are needed to confirm the clinical effectiveness of
      these drugs.

PMID- 24682762
TI  - The role of the microglia in acute CNS injury.
AB  - Microglia are considered the brain's resident immune cell involved in immune
      defense, immunocompetence, and phagocytosis. They maintain tissue homeostasis
      within the brain and spinal cord under normal condition and serves as its initial
      host defense system. However, when the central nervous system (CNS) faces injury,
      microglia respond through signaling molecules expressed or released by
      neighboring cells. Microglial responses are dual in nature. They induce a
      nonspecific immune response that may exacerbate CNS injury, especially in the
      acute stages, but are also essential to CNS recovery and repair. The full range
      of microglial mechanisms have yet to be clarified, but there is accumulating
      knowledge about microglial activation in acute CNS injury. Microglial responses
      require hours to days to fully develop, and may present a therapeutic target for
      intervention with a much longer window of opportunity compare to other
      neurological treatments. The challenge will be to find ways to selectively
      suppress the deleterious effects of microglial activation without compromising
      its beneficial functions. This review aims to provide an overview of the recent
      progress relating on the deleterious and beneficial effect of microglia in the
      setting of acute CNS injury and the potential therapeutic intervention against
      microglial activation to CNS injury. 

PMID- 24682765
TI  - A white paper--consensus and recommendations of a global harmonization team on
      assessing the impact of immunogenicity on pharmacokinetic measurements.
AB  - The Global Bioanalysis Consortium (GBC) set up an international team to explore
      the impact of immunogenicity on pharmacokinetic (PK) assessments. The intent of
      this paper is to define the field and propose best practices when developing PK
      assays for biotherapeutics. We focus on the impact of anti-drug antibodies (ADA)
      on the performance of PK assay leading to the impact on the reported drug
      concentration and exposure. The manuscript describes strategies to assess whether
      the observed change in the drug concentration is due to the ADA impact on drug
      clearance rates or is a consequence of ADA interference in the bioanalytical
      method applied to measure drug concentration. This paper provides the
      bioanalytical scientist guidance for developing ADA-tolerant PK methods. It is
      essential that the data generated in the PK, ADA, pharmacodynamic and
      efficacy/toxicity evaluations are viewed together. Therefore, the extent for the
      investigation of the PK sensitivity to the presence of ADA should be driven by
      the project needs and risk based. 

PMID- 24682766
TI  - New FDA draft guidance on immunogenicity.
AB  - A "Late Breaking" session was held on May 20 at the 2013 American Association of
      Pharmaceutical Scientists-National Biotech Conference (AAPS-NBC) to discuss the
      US Food and Drug Administration's (FDA) 2013 draft guidance on Immunogenicity
      Assessment for Therapeutic Protein Products. The session was initiated by a
      presentation from the FDA which highlighted several key aspects of the 2013 draft
      guidance pertaining to immunogenicity risk, the potential impact on patient
      safety and product efficacy, and risk mitigation. This was followed by an open
      discussion on the draft guidance which enabled delegates from biopharmaceutical
      companies to engage the FDA on topics that had emerged from their review of the
      draft guidance. The multidisciplinary audience fostered an environment that was
      conducive to scientific discussion on a broad range of topics such as clinical
      impact, immune mitigation strategies, immune prediction and the role of
      formulation, excipients, aggregates, and degradation products in immunogenicity.
      This meeting report highlights several key aspects of the 2013 draft guidance
      together with related dialog from the session. 

PMID- 24682767
TI  - A 6-year experience with 1,054 mini-gastric bypasses-first study from Indian
      subcontinent.
AB  - BACKGROUND: We started laparoscopic mini-gastric bypass (MGB) for the first time
      in India in February 2007 for its reported safety, efficacy, and easy
      reversibility. METHODS: A retrospective review of prospectively maintained data
      of all 1,054 consecutive patients (342 men and 712 women) who underwent MGB at
      our institute from February 2007 to January 2013 was done. RESULTS: Mean age was
      38.4 years, preoperative mean weight was 128.5 kg, mean BMI was 43.2 kg/m(2),
      mean operating time was 52 +/- 18.5 min, and mean hospital stay was 2.5 +/- 1.3
      days. There were 49 (4.6%) early minor complications, 14 (1.3%) major
      complications, and 2 leaks (0.2%). In late complications, one patient had low
      albumin and one had excess weight loss; MGB was easily reversed in both (0.2%).
      Marginal ulcers were noted in five patients (0.6%) during follow-up for
      symptomatic dyspepsia, and anemia was the most frequent late complication
      occurring in 68 patients (7.6%). Patient satisfaction was high, and mean excess
      weight loss was 84, 91, 88, 86, 87, and 85% at years 1 to 6, respectively.
      CONCLUSION: This study confirms previous publications showing that MGB is quite
      safe, with a short hospital stay and low risk of complications. It results in
      effective and sustained weight loss with high resolution of comorbidities and
      complications that are easily managed.

PMID- 24682769
TI  - Digitized whole slides for breast pathology interpretation: current practices and
      perceptions.
AB  - Digital whole slide imaging (WSI) is an emerging technology for pathology
      interpretation; however, little is known about pathologists' practice patterns or
      perceptions regarding WSI. A national sample (N = 252) of pathologists from New
      Hampshire, Vermont, Washington, Oregon, Arizona, Alaska, Maine, and Minnesota
      were surveyed in this cross-sectional study (2011-2013). The survey included
      questions on pathologists' experience, WSI practice patterns, and perceptions
      using a six-point Likert scale. Agreement was summarized with descriptive
      statistics to characterize pathologists' use and perceptions of WSI. The majority
      of participating pathologists were males (63%) between 40 and 59 years of age
      (70%) and not affiliated with an academic medical center (72%). Experience with
      WSI was reported by 49%. Types of use reported included CME/board exams/teaching
      (28%), tumor board/clinical conference (22%), archival purposes (6%),
      consultative diagnosis (4%), research (4%), and other uses (12%). Most
      respondents (79%) agreed that accurate diagnoses can be made with this
      technology, and that WSI is useful for obtaining a second opinion (88%). However,
      78% of pathologists agreed that digital slides are too slow for routine clinical
      interpretation. Fifty-nine percent agreed that the benefits of WSI outweigh
      concerns. The respondents were equally split as to whether they would like to
      adopt WSI (51%) or not (49%). About half of pathologists reported experience with
      the WSI technology, largely for CME, licensure/board exams, and teaching.
      Positive perceptions regarding WSI slightly outweigh negative perceptions.
      Understanding practice patterns with WSI as dissemination advances may facilitate
      concordance of perceptions with adoption of the technology.

PMID- 24682770
TI  - Identification of an isoform of colony-stimulating factor 1 receptor mRNA in the
      rat testis.
AB  - Because alternative RNA splicing regulation in the testis is prevalent, we
      explored testes of Sprague-Dawley rats for existence of alternatively spliced
      colony-stimulating factor 1 receptor (CSF-1R) mRNA. Using RT-PCR and sequencing,
      we identified a variant of CSF-1R mRNA that was 284 bp shorter than the full
      length CSF-1R transcript. This variant was present in the testis (late fetal
      stage to adult) and in other organs of rats (7 and 60 days old). The deletion of
      284 bp disrupted the open reading frame, resulting in a noncoding mRNA product.
      When testicular macrophages were stimulated with CSF-1R ligand and
      lipopolysaccharide, proportionally increased expression of both short isoform and
      full-length CSF-1R mRNA was observed. Thus, the identified isoform of CSF-1R mRNA
      may interfere with the expression of full-length CSF-1R mRNA, thereby affecting
      the biological activity of the ligand/receptor signaling axis in Sprague-Dawley
      rats.

PMID- 24682771
TI  - Good's syndrome, CVID, and selective antibody deficiency in patients with chronic
      rhinosinusitis.
AB  - Good's syndrome and common variable immune deficiency (CVID) are associated with
      chronic rhinosinusitis. Good's syndrome is characterized by
      hypogammaglobulinemia, B-cell depletion, variable defects in cellular immunity
      and thymoma. Immunodeficiency and recurrent infections can initially present
      after thymectomy. The pathogenesis can involve cytokines from bone marrow along
      with genetic defects. Intravenous gamma globulin (IVIG) restores defective
      signaling and can reestablish immune homeostasis. IVIG at regular intervals is
      the most effective way to improve the clinical symptoms and reduce patient
      mortality. Increased awareness of the clinical and immunological profile of this
      syndrome may increase its early recognition. CVID patients have
      hypogammaglobulinemia, respond to IVIG and have a dysregulated antimicrobial
      peptide response to pathogenic bacteria in the upper respiratory tract. This
      article reviewed selected literature on Good's syndrome, described an unusual
      case of Good's syndrome, CVID including SAD related to chronic rhinosinusitis. 

PMID- 24682772
TI  - Management of chronic rhinosinusitis in asthma patients: is there still a debate?
AB  - The united airway concept in which upper and lower respiratory conditions are
      present in one patient requires special consideration. There is some evidence
      linking chronic rhinosinusitis and asthma, but a good understanding of the
      pathophysiology and combined management is still lacking, a fact that leads to
      discussion. Bronchial asthma is more prevalent in patients who suffer chronic
      rhinosinusitis. On the other hand, patients with asthma have a greater prevalence
      of rhinosinusitis than patients without asthma. The effect of chronic
      rhinosinusitis in patients with or without nasal polyps on asthma treatment,
      whether medical or surgical, is controversial. Some studies show worsening, other
      trials improvement, and others no effect. Direct comparisons between surgical and
      medical treatments are few. Most of the current literature available about this
      intriguing combination does not provide a good level of evidence. Thus,
      randomized clinical trials should be performed to better understand the
      management when asthma and CRS occur together. This review aims to summarize the
      current state of this association regarding the effects of different types of
      treatment. 

PMID- 24682773
TI  - Aspirin desensitization: useful treatment for chronic rhinosinusitis with nasal
      polyps (CRSwNP) in aspirin-exacerbated respiratory disease (AERD)?
AB  - Aspirin intolerance syndrome is due to disturbances in the arachidonic acid
      metabolism implicating both the lipoxygenase and cyclooxygenase pathways. This
      results in imbalances of eicosanoid, leukotriene and prostaglandin synthesis.
      Thus, preinflammatory cysteinyl leukotrienes increase and antiinflammatory
      prostaglandins (PG) such as PGE2 decrease. Clinically, intolerance reactions to
      nonsteroidal antiinflammatory drugs (NSAIDs) can lead to different clinical
      manifestations; five phenotypes of the aspirin intolerance syndrome are listed in
      the ENDA classification. Aspirin-exacerbated respiratory disease (AERD) is the
      most common phenotype characterized by an eosinophil-dominated inflammatory
      disease of the airways that presents clinically with nasal polyps, chronic
      sinusitis and bronchial asthma. About 34 % of patients with aspirin-induced
      asthma and rhinosinusitis are thought to have AERD. Important biochemical
      findings in many AERD patients are increased basal leukotriene levels (at least
      in cell cultures) that excessively increase after intake of COX-1 inhibitors.
      Aspirin desensitization uses the repetitive application of aspirin to induce a
      tolerance to NSAIDs, especially COX-1 inhibitors. After a dose-increase phase
      reaching a threshold dose, a dose-continuation phase is performed. For
      application, the nasal, bronchial, oral and intravenous routes have been
      described. Aspirin desensitization has been proven to be efficacious and safe and
      was able to reduce the need for other medications in AERD patients. 

PMID- 24682774
TI  - Phenotype of migraine headache and migraine aura of Richard Wagner.
AB  - BACKGROUND: The headache phenotype and neurological symptoms of the German
      composer Richard Wagner (1813-1883), whose music dramas count towards the most
      frequently performed operas across the world, are previously undocumented.
      METHODS: Richard Wagner's own descriptions of his headache symptoms in his
      original writings and letters are investigated, as well as the complete diary
      records of his second wife, Cosima Wagner. RESULTS: There are manifold
      indications that Richard Wagner suffered from a severe headache disorder, which
      fulfils most likely the diagnostic criteria of migraine without aura and migraine
      with aura of ICHD-3 beta. CONCLUSIONS: Richard Wagner's life and opus can help to
      better understand the burden and suffering caused by migraine with its severe
      effects on the individual, familial and social life, the culture and community.

PMID- 24682775
TI  - Vocational rehabilitation program evaluation: comparison group challenges and the
      role of unmeasured return-to-work expectations.
AB  - PURPOSE: Despite the importance and cost of workers' compensation (WC)-based
      vocational rehabilitation (VR) programs, outcome evaluations are rare, in part
      due to the scarcity of suitable comparison groups. The aims of this study were to
      assess (1) the adequacy of a commonly recommended internal comparison group,
      i.e., workers who were eligible for but did not receive services, and (2) return
      to-work (RTW) expectations as a potential source of bias. METHODS: In this
      prospective cohort study, we used WC claims data and worker-reported RTW
      expectations to compare workers who received vocational retraining services to
      eligible workers who did not receive such services. Workers were surveyed after
      retraining eligibility determination, prior to the initiation of retraining
      activities. VR progress and RTW wage outcomes were followed for 3 years. The
      magnitude of confounding contributed by RTW expectations and other covariates was
      quantified. RESULTS: Workers who were somewhat or very certain they would RTW had
      significantly better outcomes. RTW expectations played a strong confounding role,
      reducing the retraining plan effect estimate by about 23 %, while education and
      physical capacity each changed the effect estimate by <5 %. CONCLUSIONS: RTW
      expectations predicted long-term RTW outcomes and can play a strong confounding
      role if unmeasured. We found that the internal comparison group approach,
      commonly recommended for VR program evaluation, is inappropriate for WC-based VR
      evaluations. Ultimately, there is no simple solution to the challenge of
      identifying a comparison group; however, measurement of RTW expectations, an
      easily-measured multi-dimensional construct, may be a useful addition to the VR
      evaluation toolbox.

PMID- 24682776
TI  - mTOR-mediated hyperphosphorylation of tau in the hippocampus is involved in
      cognitive deficits in streptozotocin-induced diabetic mice.
AB  - Abnormal levels of mammalian target of rapamycin (mTOR) signaling have been
      recently implicated in the pathophysiology of neurodegenerative diseases, such as
      Alzheimer's disease (AD). However, the implication of mTOR in diabetes mellitus
      (DM)-related cognitive dysfunction still remains unknown. In the present study,
      we found that phosphorylated mTOR at Ser2448, phosphorylated p70S6K at
      Thr421/Ser424 and phosphorylated tau at Ser396 were significantly increased in
      the hippocampus of streptozotocin (STZ)-induced diabetic mice when compared with
      control mice. A low dose of rapamycin was used to elucidate the role of mTOR
      signaling in DM-related cognitive deficit. Rapamycin restored abnormal
      mTOR/p70S6K signaling and attenuated the phosphorylation of tau protein in the
      hippocampus of diabetic mice. Furthermore, the spatial learning and memory
      function of diabetic mice significantly impaired compared with control mice, was
      also reversed by rapamycin. These findings indicate that mTOR/p70S6K signaling
      pathway is hyperactive in the hippocampus of STZ-induced diabetic mice and
      inhibiting mTOR signaling with rapamycin prevents the DM-related cognitive
      deficits partly through attenuating the hyperphosphorylation of tau protein. 

PMID- 24682779
TI  - Keeping the weight off: physical activity, sitting time, and weight loss
      maintenance in bariatric surgery patients 2 to 16 years postsurgery.
AB  - BACKGROUND: Bariatric surgery patients often exhibit low levels of physical
      activity (PA), despite the presumed importance of PA as an adjunct to surgery for
      successful weight loss. Little is known regarding the associations of PA and
      sedentary behaviors to weight loss outcomes in the long term following surgery.
      The objective of the study was to assess the associations of PA and sitting time
      with weight status, weight loss, and weight maintenance outcomes in bariatric
      patients 2-16 years postsurgery. METHODS: A total of 303 Roux-en-Y Gastric Bypass
      patients (73% female; mean age 47 +/- 10 years, mean 7 +/- 4 years since surgery)
      completed a telephone questionnaire. Patients reported moderate-to-vigorous PA
      (MVPA: # sessions/week >=30 min) and average daily sitting time (h/day).
      Associations with various weight outcomes were assessed. RESULTS: Only 48% of
      patients reported >=1 session/week MVPA, and mean reported sitting time was 7 +/-
      4 h/day. Neither MVPA nor sitting time was associated with weight loss outcomes
      at patients' lowest weight postsurgery. However, both MVPA and sitting time were
      independently positively and inversely, respectively, associated with total (kg)
      weight loss, % weight loss, and % excess weight loss at current weight, as well
      as weight loss maintained vs. regained, controlling for age, sex, surgery type,
      presurgery BMI, total initial weight loss, and time since surgery. CONCLUSIONS:
      Results demonstrate associations between MVPA and high sitting time and weight
      loss outcomes among bariatric patients in the long term. The implications for
      long-term weight management and concomitant health outcomes highlight the need
      for appropriate follow-up and interventions in this unique high-risk patient
      population.

PMID- 24682777
TI  - Elevated homocysteine level in first-episode schizophrenia patients--the
      relevance of family history of schizophrenia and lifetime diagnosis of cannabis
      abuse.
AB  - Accumulating evidence indicates that elevated homocysteine (Hcy) level occurs in
      first-episode schizophrenia (FES) patients. We included 56 FES patients and 53
      healthy controls (HC). Plasma level of Hcy was significantly higher in FES
      patients than HC (p = 0.044). In addition, plasma levels of high-density
      lipoproteins (HDL) and folate were significantly lower in FES than in HC (p <
      0.001). Positive family history of schizophrenia was associated with lower plasma
      HDL (p = 0.041) and vitamin B12 (p = 0.017), as well as higher level of Hcy (p =
      0.017). Patients with FES, who abused cannabis, had higher levels of Hcy (p =
      0.017), as well as lower levels of vitamin B12 (p = 0.017) and HDL (p = 0.041).
      Plasma Hcy negatively correlated with duration of untreated psychosis (r = 
      0.272, p = 0.042). There was a positive correlation between Hcy level and the
      severity of negative symptoms (r = 0.363, p = 0.006) and general psychopathology
      (r = 0.349, p = 0.008) assessed using Positive and Negative Syndrome Scale
      (PANSS). Vitamin B12 level was negatively associated with the severity of
      negative symptoms (r = -0.406, p = 0.002), while folate level negatively
      correlated with general psychopathology score (r = -0.365, p = 0.006) in PANSS.
      These results indicate that the severity of one-carbon metabolism alterations and
      HDL deficiency might be associated with family history of schizophrenia and
      cannabis abuse. Lower vitamin B12 and folate along with elevated Hcy may
      influence the severity of FES psychopathology.

PMID- 24682780
TI  - Positioning therapy for Crohn's disease.
AB  - The therapy of Crohn's disease is constantly evolving. It is widely recognized
      that clinical assessment does not stage disease activity accurately and that
      endoscopic healing is associated with improved long-term outcomes. Disease
      management is therefore transitioning to a new paradigm that includes direct
      assessment of disease severity (endoscopically in most patients), followed by
      assessment of mucosal healing. New approaches have helped optimize the use of the
      thiopurines, methotrexate and anti-TNF agents. Novel agents with different
      mechanisms of action are expanding our therapeutic armamentarium. The major
      challenge of the future will be to identify patient subgroups best suited to
      particular therapeutic approaches. In the meantime, studies of comparative
      effectiveness will be crucial in positioning therapies relative to each other. 

PMID- 24682782
TI  - The safety of long-term cryopreservation on slow-frozen early cleavage human
      embryos.
AB  - OBJECTIVE: To evaluate the impact of cryopreservation storage time on cleavage
      stage embryo survival rate, pregnancy rate, implantation rate, singleton birth
      weight, and live birth rate. METHODS: This study was a retrospective analysis,
      including 867 thaw cycles and 3,367 embryos. Women who underwent IVF-FET cycles
      between 2005 and 2012 were analyzed. The patients were divided into four groups,
      as follows: group 1 (12-23 months); group 2 (24-35 months); group 3 (36-48
      months); and group 4 (>=48 months). RESULTS: The storage time did not have a
      significant effect on survival, damage rate of the blastomeres, implantation
      rate, pregnancy rate, singleton birth weight, and live birth rate for embryos
      frozen at cleavage stages. CONCLUSION: Storage time did not influence the
      survival and pregnancy outcomes of slow-frozen early cleavage human embryos. The
      developmental potential of cryopreserved human embryos with different storage
      times does not appear to have a negative influence on further development.

PMID- 24682781
TI  - Preimplantation embryo metabolism and culture systems: experience from domestic
      animals and clinical implications.
AB  - Despite advantages of in vitro embryo production in many species, widespread use
      of this technology is limited by generally lower developmental competence of in
      vitro derived embryos compared to in vivo counterparts. Regardless, in vivo or in
      vitro gametes and embryos face and must adjust to multiple microenvironments
      especially at preimplantation stages. Moreover, the embryo has to be able to
      further adapt to environmental cues in utero to result in the birth of live and
      healthy offspring. Enormous strides have been made in understanding and meeting
      stage-specific requirements of preimplantation embryos, but interpretation of the
      data is made difficult due to the complexity of the wide array of culture systems
      and the remarkable plasticity of developing embryos that seem able to develop
      under a variety of conditions. Nevertheless, a primary objective remains meeting,
      as closely as possible, the preimplantation embryo requirements as provided in
      vivo. In general, oocytes and embryos develop more satisfactorily when cultured
      in groups. However, optimization of individual culture of oocytes and embryos is
      an important goal and area of intensive current research for both animal and
      human clinical application. Successful culture of individual embryos is of
      primary importance in order to avoid ovarian superstimulation and the associated
      physiological and psychological disadvantages for patients. This review
      emphasizes stage specific shifts in embryo metabolism and requirements and
      research to optimize in vitro embryo culture conditions and supplementation, with
      a view to optimizing embryo culture in general, and culture of single embryos in
      particular. 

PMID- 24682783
TI  - The chaperone domain BRICHOS prevents CNS toxicity of amyloid-beta peptide in
      Drosophila melanogaster.
AB  - Aggregation of the amyloid-beta peptide (Abeta) into toxic oligomers and amyloid
      fibrils is linked to the development of Alzheimer's disease (AD). Mutations of
      the BRICHOS chaperone domain are associated with amyloid disease and recent in
      vitro data show that BRICHOS efficiently delays Abeta42 oligomerization and
      fibril formation. We have generated transgenic Drosophila melanogaster flies that
      express the Abeta42 peptide and the BRICHOS domain in the central nervous system
      (CNS). Co-expression of Abeta42 and BRICHOS resulted in delayed Abeta42
      aggregation and dramatic improvements of both lifespan and locomotor function
      compared with flies expressing Abeta42 alone. Moreover, BRICHOS increased the
      ratio of soluble:insoluble Abeta42 and bound to deposits of Abeta42 in the fly
      brain. Our results show that the BRICHOS domain efficiently reduces the
      neurotoxic effects of Abeta42, although significant Abeta42 aggregation is taking
      place. We propose that BRICHOS-based approaches should be explored with an aim
      towards the future prevention and treatment of AD.

PMID- 24682785
TI  - Long-term survival with good functional capacity in unoperated complex congenital
      heart defect with balanced systemic and pulmonary circulation.

PMID- 24682784
TI  - A new mouse model of Canavan leukodystrophy displays hearing impairment due to
      central nervous system dysmyelination.
AB  - Canavan disease is a leukodystrophy caused by mutations in the ASPA gene. This
      gene encodes the enzyme that converts N-acetylaspartate into acetate and aspartic
      acid. In Canavan disease, spongiform encephalopathy of the brain causes
      progressive mental retardation, motor deficit and death. We have isolated a mouse
      with a novel ethylnitrosourea-induced mutation in Aspa. This mutant, named
      deaf14, carries a c.516T>A mutation that is predicted to cause a p.Y172X protein
      truncation. No full-length ASPA protein is produced in deaf14 brain and there is
      extensive spongy degeneration. Interestingly, we found that deaf14 mice have an
      attenuated startle in response to loud noise. The first auditory brainstem
      response peak has normal latency and amplitude but peaks II, III, IV and V have
      increased latency and decreased amplitude in deaf14 mice. Our work reveals a
      hitherto unappreciated pathology in a mouse model of Canavan disease, implying
      that auditory brainstem response testing could be used in diagnosis and to
      monitor the progression of this disease.

PMID- 24682788
TI  - Three-dimensional structure of an alkaline xylanase Xyn11A-LC from alkalophilic
      Bacillus sp. SN5 and improvement of its thermal performance by introducing
      arginines substitutions.
AB  - The alkaline xylanase Xyn11A-LC from the alkalophilic Bacillus sp. SN5 was
      expressed in E. coli, purified and crystallized. The crystal structure was
      determined at a resolution of 1.49 A. Xyn11A-LC has the beta-jelly roll structure
      typical of family 11 xylanases. To improve its thermostability and
      thermophilicity, a mutant SB3 was constructed by introducing three arginines on
      the different sides of the protein surface. SB3 increased the optimum temperature
      by 5  degrees C. The wild type and SB3 had the half-lives of 22 and 68 min at 65 
      degrees C at pH 8.0 (Tris/HCl buffer), respectively. CD spectroscopy revealed
      that the melting temperature (T m) of the wild type and SB3 were 55.3 and 66.9 
      degrees C, respectively. These results showed that the introduction of arginines
      enhance the thermophilicity and thermostability of Xyn11A-LC. 

PMID- 24682789
TI  - Two newly identified sites in the N-terminal regulatory domain of Aurora-A are
      essential for auto-inhibition.
AB  - Aurora-A, a centrosome-localized serine/threonine kinase, is over-expressed in
      multiple human cancers. We previously reported Zhang et al. (Biochem Biophys Res
      Commun 2007, 357:347-352) intramolecular inhibitory regulation of Aurora-A
      between its N-terminal (Nt) regulatory domain (amino acids 1-128, Nt) and C
      terminal catalytic domain (aa 129-403, Cd). Here, we identified two essential
      sites located on the Nt of Aurora-A (Lys 99 and Lys 119) and demonstrate that
      mutation of either residue to Gly could cause the Nt and C-terminal lobes of the
      catalytic domain in Aurora-A to form a closed conformation, resulting in a loss
      of kinase activity. This inactive conformation was reversed by adding C26 peptide
      (274-299) or Ajuba, which is a required activator of Aurora-A. Over-expression of
      either mutant induced G2/M arrest. These results provide a basis for future anti
      cancer studies targeting Aurora-A. 

PMID- 24682790
TI  - Biological evaluation of novel derivatives of the orange pigments from Monascus
      sp. as inhibitors of melanogenesis.
AB  - Nitrogenous derivatives of the two orange pigments from Monascus sp. with anti
      melanogenic activities were prepared using fermentation and chemical synthesis.
      The pigments were produced in a 5 l jar fermentor. A total of 33 derivatives were
      synthesized via incorporation of L-amino acids and amines into the pigments. Two
      derivatives with high inhibitory melanin-synthesizing activities and low cell
      toxicities were selected based on testing using B16F10 cells. Glutamic acid and
      (S)-(+)-1-amino-2-propanol derivatives showed high inhibitory activities against
      melanogenesis. Both the reaction and expression of tyrosinase, an important
      enzyme in the melanin-synthesizing pathway, were inhibited by the glutamic acid
      derivative in a dose-dependent manner. The (S)-(+)-1-amino-2-propanol derivative
      inhibited expression of tyrosinase in cells, but not the tyrosinase reaction.
      TRP1 and TRP2, other important proteins in melanin-synthesis, were not affected
      by the two derivatives.

PMID- 24682791
TI  - Impact of the configuration of a chiral, activating carrier on the
      enantioselectivity of entrapped lipase from Candida rugosa in cyclohexane.
AB  - Lipase from Candida rugosa was loaded into an amphiphilic polymer co-network
      (APCN) composed of the chiral poly[(R)-N-(1-hydroxybutan-2-yl) acrylamide] [P-(R)
      HBA] and P-(S)-HBA, respectively, linked by poly(dimethylsiloxane). The nanophase
      separated amphiphilic morphology affords a 38,000-fold activation of the enzyme
      in the esterification of 1-phenylethanol with vinyl acetate. Further, the
      enantioselectivity of the entrapped lipase was influenced by the configuration of
      the chiral, hydrophilic polymer matrix. While the APCN with the (S)-configuration
      of the APCN affords 5.4 faster conversion of the (R)-phenylethanol compared to
      the respective (S)-enantiomer, the (R)-APCN allows an only a 2.8 faster
      conversion of the (R)-enantiomer of the alcohol. Permeation-experiments reveal
      that the enantioselectivity of the reaction is at least partially caused by
      specific interactions between the substrates and the APCN. 

PMID- 24682793
TI  - Assessing inter- and intra-individual cognitive variability in patients at risk
      for cognitive impairment: the case of minimal hepatic encephalopathy.
AB  - Recent evidence reveals that inter- and intra-individual variability
      significantly affects cognitive performance in a number of neuropsychological
      pathologies. We applied a flexible family of statistical models to elucidate the
      contribution of inter- and intra-individual variables on cognitive functioning in
      healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty
      five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were
      assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive
      Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the
      mean and the intra-variability of Reaction Times (RTs) as a function of socio
      demographic and task related covariates. Furthermore, a Generalized Linear Mixed
      Model (GLMM) was fitted for modeling accuracy. When controlling for the
      covariates, patients without minimal hepatic encephalopathy (MHE) did not differ
      from patients with MHE in the low-demanding condition, both in terms of RTs and
      accuracy. Moreover, they showed a significant decline in accuracy compared to the
      control group. Compared to patients with MHE, patients without MHE showed faster
      RTs and higher accuracy only in the high-demanding condition. The results
      revealed that the application of GAMLSS and GLMM models are able to capture
      subtle cognitive alterations, previously not detected, in patients' subclinical
      pathologies. 

PMID- 24682792
TI  - Infrastructures, treatment modalities, and workload of radiation oncology
      departments in Spain with special attention to prostate cancer.
AB  - AIM: The purpose of the study was to describe infrastructures, treatment
      modalities, and workload in radiation oncology (RO) in Spain, referred
      particularly to prostate cancer (PC). METHODS: An epidemiologic, cross-sectional
      study was performed during 2008-2009. A study-specific questionnaire was sent to
      the 108 RO-registered departments. RESULTS: One hundred and two departments
      answered the survey, and six were contacted by telephone. Centers operated 236
      treatment units: 23 (9.7 %) cobalt machines, 37 (15.7 %) mono-energetic linear
      accelerators, and 176 (74.6 %) multi-energy linear accelerators. Sixty-one (56.4
      %) and 33 (30.5 %) departments, respectively, reported intensity-modulated
      radiation therapy (IMRT) and image-guided RT (IGRT) capabilities; three
      dimensional-conformal RT was used in 75.8 % of patients. Virtual simulators were
      present in 95 departments (88.0 %), 35 use conventional simulators. Fifty-one
      departments (47.2 %) have brachytherapy units, 38 (35.2 %) perform prostatic
      implants. Departments saw a mean of 24.9 new patients/week; the number of
      patients treated annually was 102,054, corresponding to 88.4 % of patients with a
      RT indication. In 56.5 % of the hospitals, multidisciplinary teams were available
      to treat PC. CONCLUSIONS: Results provide an accurate picture of current
      situation of RO in Spain, showing a trend toward the progressive introduction of
      new technologies (IMRT, IGRT, brachytherapy).

PMID- 24682794
TI  - Paleoimaging: a review of applications and challenges.
AB  - This paper reviews the contributions and current practices of paleoimaging
      modalities as applied to the bioarchaeological research setting. The paper
      provides a brief historical perspective regarding imaging approaches in this
      unique context and a description of various modalities including photography, 3D
      surface scanning, aerial imaging, LiDAR, GPR, portable radiography, endoscopy, X
      ray fluorescence, and advanced medical imaging. The paper presents a review of
      issues and applications of paleoimaging with an emphasis on specific research
      questions. A description of the limitations and challenges for paleoimaging
      within the bioarchaeological construct follows and offers support for the
      multimodal approach to paleoimaging. Interpretation of imaging data by consensus
      including paleoimagers, medical scientists and bioarchaeologists is addressed.
      The paper concludes with a look to the future of paleoimaging from an
      applications and standards development perspective. 

PMID- 24682795
TI  - Arterial calcifications from mummified materials: use of micro-CT-scan for
      histological differential diagnosis.

PMID- 24682796
TI  - Fatal lawn mower related projectile injury.
AB  - Fatal lawn mower related injuries are a relatively rare occurrence. In a forensic
      setting, the primary aim is to reconstruct the injury mechanism and establish the
      cause of death. A relatively rare, but characteristic type of injury is a so
      called projectile or missile injury. This occurs when the operator or a bystander
      is impacted by an object mobilized from the grass by the rotating mower blades.
      This type of injury often leaves only modest external trauma, which increases the
      risk of overlooking an entry wound. In this paper we present a case of a fatal
      lawn mower related projectile injury which was initially overlooked, later
      interpreted as a possible gunshot homicide, and finally identified as a lawn
      mower related projectile injury when autopsy revealed a piece of metal thread in
      the main bronchus to the right middle lobe, hemopericardium, and right-sided
      hemothorax. To our knowledge, this injury mechanism has not previously been
      reported as a cause of death. This case illustrates the importance of postmortem
      radiological imaging and interdisciplinary cooperation when establishing manner
      and cause of death in unusual cases. 

PMID- 24682797
TI  - "Shaken baby syndrome" and forensic pathology.

PMID- 24682798
TI  - Could the Shroud of Turin be an effect of post-mortem changes?

PMID- 24682799
TI  - The role of cardiac pacing in carotid sinus syndrome: a meta-analysis.
AB  - PURPOSE: Cardiac pacing can be used to treat carotid sinus syndrome (CSS), but
      clinical studies have shown conflicting results. We conducted a systematic review
      and meta-analysis to evaluate the role of pacing for CSS. METHODS: A systematic
      search of publications in PubMed, Embase, and the Cochrane Library without
      language restriction was performed. Prospective randomized studies that compared
      cardiac pacing with standard therapy or pacing with different algorithms were
      included if the recurrence of syncope or the number of falls was observed.
      RESULTS: Eight studies enrolling 540 patients were identified. In open-label
      studies, the recurrence of syncope was reduced significantly by cardiac pacing
      compared with standard therapy. The recurrence of syncope was not different
      between single- and dual-chamber pacing, but a lower rate of patients with pre
      syncope was observed in the group with dual-chamber pacing. Double-blind clinical
      studies failed to observe the role of cardiac pacing for preventing falls in
      patients with CSS. CONCLUSION: The results of meta-analysis supported the use of
      cardiac pacing for patients with dominant cardioinhibitory CSS.

PMID- 24682800
TI  - Addressing the confounding role of joint hypermobility syndrome and
      gastrointestinal involvement in postural orthostatic tachycardia syndrome.
AB  - Quantitative and qualitative abnormalities in visceral function have been
      demonstrated in postural orthostatic tachycardia syndrome. Joint hypermobility is
      frequently associated with both postural orthostatic tachycardia syndrome and
      gastrointestinal symptoms. Future studies in this area should appropriately and
      systematically control for the presence of joint hypermobility syndrome. 

PMID- 24682801
TI  - Child perceptions of parental care and overprotection in children with cancer and
      healthy children.
AB  - The primary aims of this study were to: (a) examine child perceptions of
      overprotection; and (b) explore how these perceptions relate to child health and
      adjustment. Children with a prior diagnosis of cancer (n = 205) and children
      without a history of serious illness (n = 76) reported on parental overprotective
      and caring behaviors. Children with cancer were recruited from one of four strata
      based on the elapsed time since their cancer diagnosis (1-6 months; 6-24 months;
      2-5 years; >5 years) Children also reported on symptoms of depression, anxiety,
      and posttraumatic stress. Children with cancer did not differ from healthy
      children in their perceptions of parental care or overprotection. Child distress
      was more strongly related to perceptions of care and overprotection than child's
      health status. Children with cancer do not report their parents approach to care
      and protection differently than children without a cancer history. These findings
      mirror prior research examining parental perceptions of overprotection and
      suggest that, despite the challenges of parenting a child with serious illness,
      parental protection is not significantly altered.

PMID- 24682802
TI  - Transanal TAMIS total mesorectal excision (TME)--a work in progress.

PMID- 24682803
TI  - Incision-less reversal of Hartmann's procedure.
AB  - After taking down the colostomy in a patient who has previously undergone a
      Hartmann's operation, it is possible to restore bowel continuity using the single
      port technique via the colostomy site itself. This study presents our experience
      of this approach using the glove port and standard laparoscopic instrumentation.
      Between October 2010 and October 2013, 14 patients [median age 62 years (range 42
      83 years); median body mass index 25.2 kg/m(2) (range 22.7-34.9) kg/m(2)]
      underwent attempted single-port (via colostomy site) reversal of Hartmann's. All
      but one patient had had a laparotomy for their primary surgery. The glove port
      was used with a camera and two working ports. Additional remote access was needed
      in 3 (21 %) patients [1 * 5 mm port (two patients); 2 * 5-mm ports ; 2 * 5-mm
      ports and Pfannenstiel]. Median operative time was 150 min (range 75-270 min).
      Mortality was nil. One patient required reoperation and a stoma. Median hospital
      stay was 5 days (range 2-36 days). Glove port reversal of Hartmann's is
      technically possible, though challenging if extensive adhesions are present.
      Outcomes are variable. Further studies will be needed to assess whether this is a
      safe technique. 

PMID- 24682804
TI  - Psychological outcome 4 years after restrictive bariatric surgery.
AB  - Extreme obesity is associated with severe psychiatric and somatic comorbidity and
      impairment of psychosocial functioning. Bariatric surgery is the most effective
      treatment not only with regard to weight loss but also with obesity-associated
      illnesses. Health-related psychological and psychosocial variables have been
      increasingly considered as important outcome variables of bariatric surgery.
      However, the long-term impact of bariatric surgery on psychological and
      psychosocial functioning is largely unclear. The aim of this study was to
      evaluate the relationship between the course of weight and psychological
      variables including depression, anxiety, health-related quality of life (HRQOL),
      and self-esteem up to 4 years after obesity surgery.By standardized
      questionnaires prior to (T1) and 1 year (T2), 2 years (T3), and 4 years (T4)
      after surgery, 148 patients (47 males (31.8 %), 101 females (68.2 %), mean age
      38.8 +/- 10.2 years) were assessed.On average, participants lost 24.6 % of their
      initial weight 1 year after surgery, 25.1 % after 2 years, and 22.3 % after 4
      years. Statistical analysis revealed significant improvements in depressive
      symptoms, physical dimension of quality of life, and self-esteem with peak
      improvements 1 year after surgery. These improvements were largely maintained.
      Significant correlations between weight loss and improvements in depression,
      physical aspects of HRQOL (T2, T3, and T4), and self-esteem (T3) were
      observed.Corresponding to the considerable weight loss after bariatric surgery,
      important aspects of mental health improved significantly during the 4-year
      follow-up period. However, parallel to weight regain, psychological improvements
      showed a slow but not significant decline over time.

PMID- 24682805
TI  - The impact of temperament and character inventory personality traits on long-term
      outcome of Roux-en-Y gastric bypass.
AB  - BACKGROUND: A significant proportion of patients who undergo bariatric surgery
      fail to achieve enduring weight loss. Previous studies suggest that psychosocial
      variables affect postoperative outcome, although this subject is still considered
      unclear. The purpose of this study is to further investigate the impact of
      psychosocial variables on Roux-en-Y gastric bypass (RYGB) outcomes over long-term
      follow-up. MATERIALS AND METHODS: Individuals eligible for bariatric surgery were
      evaluated using validated psychopathological scales and the Temperament and
      Character Inventory in a specialized clinic for bariatric treatment. Adult
      patients who had RYGB were selected for the study. Percent of excess weight loss
      (%EWL) was measured after surgery at 6 months, 1 year, 2 years, and on the last
      clinical observation. RESULTS: This study included 333 subjects who had RYGB.
      Before surgery, mean age was 35.4 years (+/-9.5) and mean BMI was 43.3 kg/m(2)
      (+/-4.8). Higher baseline age and BMI were associated with lower %EWL across
      endpoints, although this association diminished over time. Follow up at 2 years
      and on the last clinical observation demonstrated that lower scores on the
      persistence personality variable and lower body dissatisfaction before surgery
      predicted lower %EWL. CONCLUSIONS: Psychosocial variables and personality traits
      assessed during preoperative evaluation significantly predicted weight loss after
      bariatric surgery. Greater impact was observed in long-term follow-up at 2 years.
      These findings provide guidance in identifying patients at risk for worse
      outcomes and designing interventions to improve long-term weight loss.

PMID- 24682806
TI  - Role of slow delayed rectifying potassium current in dynamics of repolarization
      and electrical memory in swine ventricles.
AB  - Dynamics of repolarization, quantified as restitution and electrical memory,
      impact conduction stability. Relatively less is known about role of slow delayed
      rectifying potassium current, I(Ks), in dynamics of repolarization and memory
      compared to the rapidly activating current I(Kr). Trans-membrane potentials were
      recorded from right ventricular tissues from pigs during reduction (chromanol
      293B) and increases in I(Ks) (mefenamic acid). A novel pacing protocol was used
      to explicitly control diastolic intervals to quantify memory. Restitution
      hysteresis, a consequence of memory, increased after chromanol 293B (loop
      thickness and area increased 27 and 38 %) and decreased after mefenamic acid (52
      and 53 %). Standard and dynamic restitutions showed an increase in average slope
      after chromanol 293B and a decrease after mefenamic acid. Increase in slope and
      memory are hypothesized to have opposite effects on electrical stability;
      therefore, these results suggest that reduction and enhancement of I(Ks) likely
      also have offsetting components that affect stability.

PMID- 24682807
TI  - Cerebral blood flow and neurovascular coupling during static exercise.
AB  - The effect of static exercise on neurovascular coupling (NVC) was investigated by
      measuring the blood flow velocity in the posterior cerebral artery (PCAv) during
      2-min static handgrip exercises (HG) at 30 % of the maximum voluntary contraction
      in 17 healthy males. NVC was estimated as the relative change in PCAv from eye
      closing to a peak response to looking at a reversed checkerboard. The conductance
      index (CI) was calculated by dividing PCAv by the mean arterial pressure (MAP).
      HG significantly increased PCAv from the resting baseline, with an increase in
      MAP and a reduction in CI, whereas NVC did not differ significantly between the
      resting and HG. Compared to the resting baseline, HG significantly increased the
      pressor response to visual stimulation by 5.6 +/- 1.1 (mean +/- SE) mmHg, while
      the CI response was significantly inhibited by -7.0 +/- 1.5 %. These results
      indicate that NVC was maintained during HG via contributions from both the
      pressor response and vasodilatation.

PMID- 24682808
TI  - Study of television viewing habits in children.
AB  - Previous studies from developing countries have reported that Television (TV)
      viewing, if excessive and of poor quality has a proven negative influence on
      child health. Indian studies on this subject are few. The present study aimed at
      determining TV viewing habits of children and their families as well as parental
      perspectives on the impact of TV on child health using a provider completed
      indigenously developed questionnaire in Hindi. The study group comprised of 109
      children attending a government hospital who belonged predominantly to lower
      socio-economic strata with poor maternal literacy. It was observed that 100 %
      children watched excessive TV (> 2 h daily), with majority viewing unsupervised
      and low quality content. There were minimal parental restrictions and no active
      discussion regarding contents. Negative impact was found on play, hobbies, sleep
      hygiene and eating habits in most children. Most parents were unaware of
      unhealthy viewing and the associated deleterious effects. As pediatricians we
      need to enquire about TV viewing habits routinely and educate parents about
      appropriate TV viewing.

PMID- 24682809
TI  - 'Isolated Rapunzel tail' presenting as acute appendicitis.

PMID- 24682810
TI  - Delivering Sprinkles Plus through the Integrated Child Development Services
      (ICDS) to reduce anemia in pre-school children in India: correspondence.

PMID- 24682811
TI  - Delivering Sprinkles Plus through the Integrated Child Development Services
      (ICDS) to reduce anemia in pre-school children in India: author's reply.

PMID- 24682812
TI  - Large-scale analysis of tandem repeat variability in the human genome.
AB  - Tandem repeats are short DNA sequences that are repeated head-to-tail with a
      propensity to be variable. They constitute a significant proportion of the human
      genome, also occurring within coding and regulatory regions. Variation in these
      repeats can alter the function and/or expression of genes allowing organisms to
      swiftly adapt to novel environments. Importantly, some repeat expansions have
      also been linked to certain neurodegenerative diseases. Therefore, accurate
      sequencing of tandem repeats could contribute to our understanding of common
      phenotypic variability and might uncover missing genetic factors in idiopathic
      clinical conditions. However, despite long-standing evidence for the functional
      role of repeats, they are largely ignored because of technical limitations in
      sequencing, mapping and typing. Here, we report on a novel capture technique and
      data filtering protocol that allowed simultaneous sequencing of thousands of
      tandem repeats in the human genomes of a three generation family using GS-FLX
      plus Titanium technology. Our results demonstrated that up to 7.6% of tandem
      repeats in this family (4% in coding sequences) differ from the reference
      sequence, and identified a de novo variation in the family tree. The method opens
      new routes to look at this underappreciated type of genetic variability,
      including the identification of novel disease-related repeats. 

PMID- 24682813
TI  - A role for WDR5 in TRA-1/Gli mediated transcriptional control of the sperm/oocyte
      switch in C. elegans.
AB  - The hermaphrodite germline of Caenorhabditis elegans initially engages in
      spermatogenesis and then switches to oogenesis during late stages of larval
      development. TRA-1, a member of the Ci/Gli family of transcriptional repressors,
      plays an essential role in this switch by repressing genes that promote
      spermatogenesis. WDR5 proteins are conserved components of histone
      methyltransferase complexes normally associated with gene activation. However,
      two C. elegans WDR5 homologs, wdr-5.1 and wdr-5.2 are redundantly required for
      normal TRA-1 dependent repression, and this function is independent of their
      roles in histone methylation. Animals lacking wdr-5.1/wdr-5.2 function fail to
      switch to oogenesis at 25 degrees C, resulting in a masculinization of germline
      (Mog) phenotype. The Mog phenotype is caused by ectopic expression of fog-3, a
      direct target of TRA-1 repression. WDR-5.1 associates with the fog-3 promoter and
      is required for TRA-1 to bind to fog-3 promoter. Other direct targets of TRA-1
      are similarly derepressed in the double mutant. These results show that WDR5
      plays a novel and important role in stabilizing transcriptional repression during
      C. elegans sex determination, and provide evidence that this important protein
      may operate independently of its established role in histone methyltransferase
      complexes. 

PMID- 24682814
TI  - A eukaryotic-like 3' untranslated region in Salmonella enterica hilD mRNA.
AB  - Long 3' untranslated regions (3'UTRs) are common in eukaryotic mRNAs. In
      contrast, long 3'UTRs are rare in bacteria, and have not been characterized in
      detail. We describe a 3'UTR of 310 nucleotides in hilD mRNA, a transcript that
      encodes a transcriptional activator of Salmonella enterica pathogenicity island 1
      (SPI-1). Deletion of the hilD 3'UTR increases the hilD mRNA level, suggesting
      that the hilD 3'UTR may play a role in hilD mRNA turnover. Cloning of the hilD
      3'UTR downstream of the green fluorescent protein (gfp) gene decreases green
      fluorescent protein (GFP) activity in both Escherichia coli and S. enterica,
      indicating that the hilD 3'UTR can act as an independent module. S. enterica
      mutants lacking either ribonuclease E or polynucleotide phosphorylase contain
      similar amounts of hilD and hilD Delta3'UTR mRNAs, suggesting that the hilD 3'UTR
      is a target for hilD mRNA degradation by the degradosome. The hilD 3'UTR is also
      necessary for modulation of hilD and SPI-1 expression by the RNA chaperone Hfq.
      Overexpression of SPI-1 in the absence of the hilD 3'UTR retards Salmonella
      growth and causes uncontrolled invasion of epithelial cells. Based on these
      observations, we propose that the S. enterica hilD 3'UTR is a cis-acting element
      that contributes to cellular homeostasis by promoting hilD mRNA turnover. 

PMID- 24682815
TI  - Bi-Force: large-scale bicluster editing and its application to gene expression
      data biclustering.
AB  - The explosion of the biological data has dramatically reformed today's biological
      research. The need to integrate and analyze high-dimensional biological data on a
      large scale is driving the development of novel bioinformatics approaches.
      Biclustering, also known as 'simultaneous clustering' or 'co-clustering', has
      been successfully utilized to discover local patterns in gene expression data and
      similar biomedical data types. Here, we contribute a new heuristic: 'Bi-Force'.
      It is based on the weighted bicluster editing model, to perform biclustering on
      arbitrary sets of biological entities, given any kind of pairwise similarities.
      We first evaluated the power of Bi-Force to solve dedicated bicluster editing
      problems by comparing Bi-Force with two existing algorithms in the BiCluE
      software package. We then followed a biclustering evaluation protocol in a recent
      review paper from Eren et al. (2013) (A comparative analysis of biclustering
      algorithms for gene expressiondata. Brief. Bioinform., 14:279-292.) and compared
      Bi-Force against eight existing tools: FABIA, QUBIC, Cheng and Church, Plaid,
      BiMax, Spectral, xMOTIFs and ISA. To this end, a suite of synthetic datasets as
      well as nine large gene expression datasets from Gene Expression Omnibus were
      analyzed. All resulting biclusters were subsequently investigated by Gene
      Ontology enrichment analysis to evaluate their biological relevance. The distinct
      theoretical foundation of Bi-Force (bicluster editing) is more powerful than
      strict biclustering. We thus outperformed existing tools with Bi-Force at least
      when following the evaluation protocols from Eren et al. Bi-Force is implemented
      in Java and integrated into the open source software package of BiCluE. The
      software as well as all used datasets are publicly available at http://biclue.mpi
      inf.mpg.de. 

PMID- 24682816
TI  - Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for
      highly accurate CNV and SNP/INDEL detection.
AB  - Despite declining sequencing costs, few methods are available for cost-effective
      single-nucleotide polymorphism (SNP), insertion/deletion (INDEL) and copy number
      variation (CNV) discovery in a single assay. Commercially available methods
      require a high investment to a specific region and are only cost-effective for
      large samples. Here, we introduce a novel, flexible approach for multiplexed
      targeted sequencing and CNV analysis of large genomic regions called multiplexed
      direct genomic selection (MDiGS). MDiGS combines biotinylated bacterial
      artificial chromosome (BAC) capture and multiplexed pooled capture for SNP/INDEL
      and CNV detection of 96 multiplexed samples on a single MiSeq run. MDiGS is
      advantageous over other methods for CNV detection because pooled sample capture
      and hybridization to large contiguous BAC baits reduces sample and probe
      hybridization variability inherent in other methods. We performed MDiGS capture
      for three chromosomal regions consisting of ~ 550 kb of coding and non-coding
      sequence with DNA from 253 patients with congenital lower limb disorders. PITX1
      nonsense and HOXC11 S191F missense mutations were identified that segregate in
      clubfoot families. Using a novel pooled-capture reference strategy, we identified
      recurrent chromosome chr17q23.1q23.2 duplications and small HOXC 5' cluster
      deletions (51 kb and 12 kb). Given the current interest in coding and non-coding
      variants in human disease, MDiGS fulfills a niche for comprehensive and low-cost
      evaluation of CNVs, coding, and non-coding variants across candidate regions of
      interest.

PMID- 24682817
TI  - Distinct Z-DNA binding mode of a PKR-like protein kinase containing a Z-DNA
      binding domain (PKZ).
AB  - Double-stranded ribonucleic acid-activated protein kinase (PKR) downregulates
      translation as a defense mechanism against viral infection. In fish species, PKZ,
      a PKR-like protein kinase containing left-handed deoxyribonucleic acid (Z-DNA)
      binding domains, performs a similar role in the antiviral response. To understand
      the role of PKZ in Z-DNA recognition and innate immune response, we performed
      structural and functional studies of the Z-DNA binding domain (Zalpha) of PKZ
      from Carassius auratus (caZalphaPKZ). The 1.7-A resolution crystal structure of
      caZalphaPKZ:Z-DNA revealed that caZalphaPKZ shares the overall fold with other
      Zalpha, but has discrete structural features that differentiate its DNA binding
      mode from others. Functional analyses of caZalphaPKZ and its mutants revealed
      that caZalphaPKZ mediates the fastest B-to-Z transition of DNA among Zalpha, and
      the minimal interaction for Z-DNA recognition is mediated by three backbone
      phosphates and six residues of caZalphaPKZ. Structure-based mutagenesis and B-to
      Z transition assays confirmed that Lys56 located in the beta-wing contributes to
      its fast B-to-Z transition kinetics. Investigation of the DNA binding kinetics of
      caZalphaPKZ further revealed that the B-to-Z transition rate is positively
      correlated with the association rate constant. Taking these results together, we
      conclude that the positive charge in the beta-wing largely affects fast B-to-Z
      transition activity by enhancing the DNA binding rate. 

PMID- 24682818
TI  - Modulating TRAP-mediated transcription termination by AT during transcription of
      the leader region of the Bacillus subtilis trp operon.
AB  - An 11-subunit protein called trp RNA binding Attenuation Protein (TRAP) controls
      attenuation of the tryptophan biosynthetic (trpEDCFBA) operon in Bacillus
      subtilis. Tryptophan-activated TRAP binds to 11 (G/U)AG repeats in the 5' leader
      region of trp mRNAs, and downregulates expression of the operon by promoting
      transcription termination prior to the structural genes. Anti-TRAP (AT) is an
      antagonist that binds to tryptophan-activated TRAP and prevents TRAP from binding
      to RNA, thereby upregulating expression of the trp genes. AT forms trimers, and
      multiple trimers bind to a TRAP 11mer. It is not known how many trimers must bind
      to TRAP in order to interfere with RNA binding. Studies of isolated TRAP and AT
      showed that AT can prevent TRAP from binding to the trp leader RNA but cannot
      dissociate a pre-formed TRAP-RNA complex. Here, we show that AT can prevent TRAP
      mediated termination of transcription by inducing dissociation of TRAP from the
      nascent RNA when it has bound to fewer than all 11 (G/U)AG repeats. The 5'-most
      region of the TRAP binding site in the nascent transcript is most susceptible to
      dissociation from TRAP. We also show that one AT trimer bound to TRAP 11mer
      reduces the affinity of TRAP for RNA and eliminates TRAP-mediated transcription
      termination in vitro. 

PMID- 24682819
TI  - Functional redundancy between the transcriptional activation domains of E2A is
      mediated by binding to the KIX domain of CBP/p300.
AB  - The E-protein transcription factors play essential roles in lymphopoiesis, with
      E12 and E47 (hereafter called E2A) being particularly important in B cell
      specification and maturation. The E2A gene is also involved in a chromosomal
      translocation that results in the leukemogenic oncoprotein E2A-PBX1. The two
      activation domains of E2A, AD1 and AD2, display redundant, independent, and
      cooperative functions in a cell-dependent manner. AD1 of E2A functions by binding
      the transcriptional co-activator CBP/p300; this interaction is required in
      oncogenesis and occurs between the conserved phi-x-x-phi-phi motif in AD1 and the
      KIX domain of CBP/p300. However, co-activator recruitment by AD2 has not been
      characterized. Here, we demonstrate that the first of two conserved phi-x-x-phi
      phi motifs within AD2 of E2A interacts at the same binding site on KIX as AD1.
      Mutagenesis uncovered a correspondence between the KIX-binding affinity of AD2
      and transcriptional activation. Although AD2 is dispensable for oncogenesis,
      experimentally increasing the affinity of AD2 for KIX uncovered a latent
      potential to mediate immortalization of primary hematopoietic progenitors by E2A
      PBX1. Our findings suggest that redundancy between the two E2A activation domains
      with respect to transcriptional activation and oncogenic function is mediated by
      binding to the same surface of the KIX domain of CBP/p300. 

PMID- 24682821
TI  - Explaining the correlations among properties of mammalian promoters.
AB  - Proximal promoters are fundamental genomic elements for gene expression. They
      vary in terms of GC percentage, CpG abundance, presence of TATA signal,
      evolutionary conservation, chromosomal spread of transcription start sites and
      breadth of expression across cell types. These properties are correlated, and it
      has been suggested that there are two classes of promoters: one class with high
      CpG, widely spread transcription start sites and broad expression, and another
      with TATA signals, narrow spread and restricted expression. However, it has been
      unclear why these properties are correlated in this way. We reexamined these
      features using the deep FANTOM5 CAGE data from hundreds of cell types. First, we
      point out subtle but important biases in previous definitions of promoters and of
      expression breadth. Second, we show that most promoters are rather
      nonspecifically expressed across many cell types. Third, promoters' expression
      breadth is independent of maximum expression level, and therefore correlates with
      average expression level. Fourth, the data show a more complex picture than two
      classes, with a network of direct and indirect correlations among promoter
      properties. By tentatively distinguishing the direct from the indirect
      correlations, we reveal simple explanations for them. 

PMID- 24682820
TI  - Molecular dissection of the domain architecture and catalytic activities of human
      PrimPol.
AB  - PrimPol is a primase-polymerase involved in nuclear and mitochondrial DNA
      replication in eukaryotic cells. Although PrimPol is predicted to possess an
      archaeo-eukaryotic primase and a UL52-like zinc finger domain, the role of these
      domains has not been established. Here, we report that the proposed zinc finger
      domain of human PrimPol binds zinc ions and is essential for maintaining primase
      activity. Although apparently dispensable for its polymerase activity, the zinc
      finger also regulates the processivity and fidelity of PrimPol's extension
      activities. When the zinc finger is disrupted, PrimPol becomes more promutagenic,
      has an altered translesion synthesis spectrum and is capable of faithfully
      bypassing cyclobutane pyrimidine dimer photolesions. PrimPol's polymerase domain
      binds to both single- and double-stranded DNA, whilst the zinc finger domain
      binds only to single-stranded DNA. We additionally report that although PrimPol's
      primase activity is required to restore wild-type replication fork rates in
      irradiated PrimPol-/- cells, polymerase activity is sufficient to maintain
      regular replisome progression in unperturbed cells. Together, these findings
      provide the first analysis of the molecular architecture of PrimPol, describing
      the activities associated with, and interplay between, its functional domains and
      defining the requirement for its primase and polymerase activities during nuclear
      DNA replication.

PMID- 24682822
TI  - Boronic acid-mediated polymerase chain reaction for gene- and fragment-specific
      detection of 5-hydroxymethylcytosine.
AB  - The gene- or fragment-specific detection of newly recognized deoxyribonucleic
      acid (DNA) base 5-hydroxymethylcytosine (5hmC) will provide insights into its
      critical functions in development and diseases, and is also important for
      screening 5hmC-rich genes as an indicator of epigenetic states, pathogenic
      processes and pharmacological responses. Current analytical technologies for gene
      specific detection of 5hmC are heavily dependent on glucosylated 5hmC-resistant
      restriction endonuclease cleavage. Here, we find that boronic acid (BA) can
      inhibit the amplification activity of Taq DNA polymerase for replicating
      glucosylated 5hmC bases in template DNA by interacting with their glucose moiety.
      On the basis of this finding, we propose for the first time a BA-mediated
      polymerase chain reaction (PCR) assay for rapid and sensitive detection of gene-
      or fragment-specific 5hmC without restriction-assay-like sequence limitations. To
      optimize the BA-mediated PCR assay, we further tested BA derivatives and show
      that one BA derivative, 2-(2'-chlorobenzyloxy) phenylboronic acid, displays the
      highest inhibitory efficiency. Using the optimized assay, we demonstrate the
      enrichment of 5hmC in an intron region of Pax5 gene (a member of the paired box
      family of transcription factors) in mouse embryonic stem cells. Our work
      potentially opens a new way for the screening and identification of 5hmC-rich
      genes and for high throughput analysis of 5hmC in mammalian cells. 

PMID- 24682823
TI  - CompaRNA: a server for continuous benchmarking of automated methods for RNA
      secondary structure prediction.

PMID- 24682824
TI  - Imogene: identification of motifs and cis-regulatory modules underlying gene co
      regulation.
AB  - Cis-regulatory modules (CRMs) and motifs play a central role in tissue and
      condition-specific gene expression. Here we present Imogene, an ensemble of
      statistical tools that we have developed to facilitate their identification and
      implemented in a publicly available software. Starting from a small training set
      of mammalian or fly CRMs that drive similar gene expression profiles, Imogene
      determines de novo cis-regulatory motifs that underlie this co-expression. It can
      then predict on a genome-wide scale other CRMs with a regulatory potential
      similar to the training set. Imogene bypasses the need of large datasets for
      statistical analyses by making central use of the information provided by the
      sequenced genomes of multiple species, based on the developed statistical tools
      and explicit models for transcription factor binding site evolution. We test
      Imogene on characterized tissue-specific mouse developmental CRMs. Its ability to
      identify CRMs with the same specificity based on its de novo created motifs is
      comparable to that of previously evaluated 'motif-blind' methods. We further
      show, both in flies and in mammals, that Imogene de novo generated motifs are
      sufficient to discriminate CRMs related to different developmental programs.
      Notably, purely relying on sequence data, Imogene performs as well in this
      discrimination task as a previously reported learning algorithm based on
      Chromatin Immunoprecipitation (ChIP) data for multiple transcription factors at
      multiple developmental stages. 

PMID- 24682825
TI  - Progressive engineering of a homing endonuclease genome editing reagent for the
      murine X-linked immunodeficiency locus.
AB  - LAGLIDADG homing endonucleases (LHEs) are compact endonucleases with 20-22 bp
      recognition sites, and thus are ideal scaffolds for engineering site-specific DNA
      cleavage enzymes for genome editing applications. Here, we describe a general
      approach to LHE engineering that combines rational design with directed
      evolution, using a yeast surface display high-throughput cleavage selection. This
      approach was employed to alter the binding and cleavage specificity of the I-Anil
      LHE to recognize a mutation in the mouse Bruton tyrosine kinase (Btk) gene
      causative for mouse X-linked immunodeficiency (XID)-a model of human X-linked
      agammaglobulinemia (XLA). The required re-targeting of I-AniI involved
      progressive resculpting of the DNA contact interface to accommodate nine base
      differences from the native cleavage sequence. The enzyme emerging from the
      progressive engineering process was specific for the XID mutant allele versus the
      wild-type (WT) allele, and exhibited activity equivalent to WT I-AniI in vitro
      and in cellulo reporter assays. Fusion of the enzyme to a site-specific DNA
      binding domain of transcription activator-like effector (TALE) resulted in a
      further enhancement of gene editing efficiency. These results illustrate the
      potential of LHE enzymes as specific and efficient tools for therapeutic genome
      engineering. 

PMID- 24682826
TI  - A high-throughput chemical screen with FDA approved drugs reveals that the
      antihypertensive drug Spironolactone impairs cancer cell survival by inhibiting
      homology directed repair.
AB  - DNA double-strand breaks (DSBs) are the most severe type of DNA damage. DSBs are
      repaired by non-homologous end-joining or homology directed repair (HDR).
      Identifying novel small molecules that affect HDR is of great importance both for
      research use and therapy. Molecules that elevate HDR may improve gene targeting
      whereas inhibiting molecules can be used for chemotherapy, since some of the
      cancers are more sensitive to repair impairment. Here, we performed a high
      throughput chemical screen for FDA approved drugs, which affect HDR in cancer
      cells. We found that HDR frequencies are increased by retinoic acid and
      Idoxuridine and reduced by the antihypertensive drug Spironolactone. We further
      revealed that Spironolactone impairs Rad51 foci formation, sensitizes cancer
      cells to DNA damaging agents, to Poly (ADP-ribose) polymerase (PARP) inhibitors
      and cross-linking agents and inhibits tumor growth in xenografts, in mice. This
      study suggests Spironolactone as a new candidate for chemotherapy. 

PMID- 24682827
TI  - Structural and functional studies of Stf76 from the Sulfolobus islandicus plasmid
      virus pSSVx: a novel peculiar member of the winged helix-turn-helix transcription
      factor family.
AB  - The hybrid plasmid-virus pSSVx from Sulfolobus islandicus presents an open
      reading frame encoding a 76 amino acid protein, namely Stf76, that does not show
      significant sequence homology with any protein with known 3D structure. The
      recombinant protein recognizes specifically two DNA-binding sites located in its
      own promoter, thus suggesting an auto-regulated role of its expression. Circular
      dichroism, spectrofluorimetric, light scattering and isothermal titration
      calorimetry experiments indicated a 2:1 molar ratio (protein:DNA) upon binding to
      the DNA target containing a single site. Furthermore, the solution structure of
      Stf76, determined by nuclear magnetic resonance (NMR) using chemical shift
      Rosetta software, has shown that the protein assumes a winged helix-turn-helix
      fold. NMR chemical shift perturbation analysis has been performed for the
      identification of the residues responsible for DNA interaction. In addition, a
      model of the Stf76-DNA complex has been built using as template a structurally
      related homolog. 

PMID- 24682828
TI  - Structure, dynamics and RNA binding of the multi-domain splicing factor TIA-1.
AB  - Alternative pre-messenger ribonucleic acid (pre-mRNA) splicing is an essential
      process in eukaryotic gene regulation. The T-cell intracellular antigen-1 (TIA-1)
      is an apoptosis-promoting factor that modulates alternative splicing of
      transcripts, including the pre-mRNA encoding the membrane receptor Fas. TIA-1 is
      a multi-domain ribonucleic acid (RNA) binding protein that recognizes poly
      uridine tract RNA sequences to facilitate 5' splice site recognition by the U1
      small nuclear ribonucleoprotein (snRNP). Here, we characterize the RNA
      interaction and conformational dynamics of TIA-1 by nuclear magnetic resonance
      (NMR), isothermal titration calorimetry (ITC) and small angle X-ray scattering
      (SAXS). Our NMR-derived solution structure of TIA-1 RRM2-RRM3 (RRM2,3) reveals
      that RRM2 adopts a canonical RNA recognition motif (RRM) fold, while RRM3 is
      preceded by an non-canonical helix alpha0. NMR and SAXS data show that all three
      RRMs are largely independent structural modules in the absence of RNA, while RNA
      binding induces a compact arrangement. RRM2,3 binds to pyrimidine-rich FAS pre
      mRNA or poly-uridine (U9) RNA with nanomolar affinities. RRM1 has little
      intrinsic RNA binding affinity and does not strongly contribute to RNA binding in
      the context of RRM1,2,3. Our data unravel the role of binding avidity and the
      contributions of the TIA-1 RRMs for recognition of pyrimidine-rich RNAs. 

PMID- 24682829
TI  - Recombination hotspots attenuate the coupled ATPase and translocase activities of
      an AddAB-type helicase-nuclease.
AB  - In all domains of life, the resection of double-stranded DNA breaks to form long
      3'-ssDNA overhangs in preparation for recombinational repair is catalyzed by the
      coordinated activities of DNA helicases and nucleases. In bacterial cells, this
      resection reaction is modulated by the recombination hotspot sequence Chi. The
      Chi sequence is recognized in cis by translocating helicase-nuclease complexes
      such as the Bacillus subtilis AddAB complex. Binding of Chi to AddAB results in
      the attenuation of nuclease activity on the 3'-terminated strand, thereby
      promoting recombination. In this work, we used stopped-flow methods to monitor
      the coupling of adenosine triphosphate (ATP) hydrolysis and DNA translocation and
      how this is affected by Chi recognition. We show that in the absence of Chi
      sequences, AddAB translocates processively on DNA at ~2000 bp s(-1) and
      hydrolyses approximately 1 ATP molecule per base pair travelled. The recognition
      of recombination hotspots results in a sustained decrease in the translocation
      rate which is accompanied by a decrease in the ATP hydrolysis rate, such that the
      coupling between these activities and the net efficiency of DNA translocation is
      largely unchanged by Chi. 

PMID- 24682830
TI  - Neuregulin-1 signaling in the pathogenesis of chemotherapy-induced heart failure.
AB  - The National Cancer Institute estimates that approximately 13.7 million Americans
      with a history of cancer were alive on January 1, 2012. With the rising number of
      cancer survivors, there is an increased focus on how chemotherapy agents modulate
      the cardiovascular biology and cause chemotherapy-related heart failure in
      certain patients. Neuregulin-1 (NRG-1) is an important cardiac growth factor that
      is essential for normal myocardial development and maintenance. Certain
      chemotherapy agents perturb the normal NRG-1 signaling in the cardiovascular
      system and cause cardiac dysfunction and, in some cases, symptomatic heart
      failure. As researchers have learned the critical importance of NRG-1 within the
      cardiovascular system, more attention has been focused on the potential use of
      NRG-1 as biomarker and therapy for the treatment of heart failure. This review
      will highlight the biology of NRG-1 within the cardiovascular system, its role in
      chemotherapy-induced heart failure, and the translational potential of NRG-1 as
      treatment for heart failure. 

PMID- 24682831
TI  - Heart failure and obesity in adults: pathophysiology, clinical manifestations and
      management.
AB  - Obesity is both a risk factor and a direct cause of heart failure (HF) in adults.
      Severe obesity produces hemodynamic alterations that predispose to changes in
      left ventricular morphology and function, which, over time, may lend to the
      development of HF (obesity cardiomyopathy). Certain neurohormonal and metabolic
      abnormalities as well as cardiovascular co-morbidities may facilitate this
      process. Substantial purposeful weight loss is capable of reversing most of the
      alterations in cardiac performance and morphology and may improve functional
      capacity and quality of life in patents with obesity cardiomyopathy. 

PMID- 24682833
TI  - Keep your sunny side: a street-level look at homelessness.
AB  - This opinion piece considers my personal experiences of poverty, homelessness,
      loss, and physical disability in relation to recent discussions of social defeat
      and resistance among permanent supported housing tenants with physical and mental
      illnesses. By drawing attention to the onslaught of deprivation and humiliation
      that generally comes with the territory of poverty and homelessness in the United
      States, I hope to influence the ways in which clinicians, social service
      providers, and scholars think about specific instances of social defeat and
      resistance. My basic point is that any specific experience of resistance or
      defeat cannot be adequately understood in isolation. Rather, such experiences
      must be understood in relation to individual life histories of defeat and
      resistance, and to the symbolic and material sources of success and failure
      available to citizens who occupy a particular section of social space in a given
      society. 

PMID- 24682832
TI  - Type 1 diabetes in mice and men: gene expression profiling to investigate disease
      pathogenesis.
AB  - Type 1 diabetes (T1D) is a complex polygenic disease that is triggered by various
      environmental factors in genetically susceptible individuals. The emphasis placed
      on genome-wide association studies to explain the genetics of T1D has failed to
      advance our understanding of T1D pathogenesis or identify biomarkers of disease
      progression or therapeutic targets. Using the nonobese diabetic (NOD) mouse model
      of T1D and the non-disease prone congenic NOD.B10 mice, our laboratory
      demonstrated striking tissue-specific and age-dependent changes in gene
      expression during disease progression. We established a "roadmap" of differential
      gene expression and used this to identify candidate genes in mice (and human
      orthologs) that play a role in disease pathology. Here, we describe two genes,
      Deformed epidermal autoregulatory factor 1 (Deaf1) and Adenosine A1 receptor
      (Adora1), that are differentially expressed and alternatively spliced in the
      pancreatic lymph nodes or islets of NOD mice and T1D patients to form dominant
      negative non-functional isoforms. Loss of Deaf1 function leads to reduced
      peripheral tissue antigen expression in lymph node stromal cells and may
      contribute to a breakdown in peripheral tolerance, while reduced Adora1 function
      results in an early intrinsic alpha cell defect that may explain the
      hyperglucagonemia and resulting beta cell stress observed prior to the onset of
      diabetes. Remarkably, both genes were also alternatively spliced in the same
      tissues of auto-antibody positive prediabetic patients, and these splicing events
      resulted in similar downstream effects as those seen in NOD mice. These findings
      demonstrate the value of gene expression profiling in studying disease
      pathogenesis in T1D.

PMID- 24682834
TI  - Is vitamin D deficiency a cause of increased morbidity and mortality at older age
      or simply an indicator of poor health?
AB  - To assess whether vitamin D deficiency is a cause of increased morbidity and
      mortality or simply an indicator of poor health, we assessed (1) the cross
      sectional and longitudinal association of vitamin D deficiency with self-rated
      health (SRH) and frailty and (2) the association of vitamin D deficiency with
      mortality, with and without control for SRH and frailty. Analyses were performed
      in 9,579 participants of the German, population-based ESTHER cohort (age-range at
      baseline: 50-74 years), with follow-ups after 2, 5 and 8 years (mortality: 12
      years). During follow-up, 129 subjects newly reported poor SRH, 510 developed
      frailty and 1,450 died. In cross-sectional analyses, subjects with vitamin D
      deficiency had higher odds of a poor SRH and frailty but no association with SRH
      or frailty was observed in longitudinal analyses. The association of vitamin D
      deficiency with all-cause and several cause-specific mortalities was strong and
      unaltered by time-dependent adjustment for classic mortality risk factors, SRH
      and frailty. In conclusion, vitamin D deficiency may not cause frailty or poor
      general health but may nevertheless be a prognostic marker for mortality,
      independent of the individual's morbidity. 

PMID- 24682836
TI  - Plagiarism and health promotion: an ounce of prevention is worth a pound of cure.

PMID- 24682835
TI  - Review of the antenatal and postnatal use of steroids.
AB  - Antenatal and postnatal corticosteroids play an extremely important role in the
      management of premature infants. The antenatal administration of steroids has
      been universally implemented. They have not only been shown to reduce the
      incidence and severity of respiratory distress syndrome (RDS), but also have an
      impact on the incidence of intraventricular hemorrhage (IVH), patent ductus
      arteriosus (PDA), necrotizing enterocolitis (NEC), and possibly retinopathy of
      prematurity (ROP) by reducing the need for supplemental oxygen due to improved
      lung function. The postnatal use of dexamethasone in ventilated infants has been
      adopted with caution, as there have been several reports of long-term
      neurodevelopmental complications with this therapy. Hence, changes in dosage and
      indications and the search for alternative therapies has emerged. Hydrocortisone
      appears to be a good alternative, with reassuring long-term evaluations thus far.

PMID- 24682837
TI  - Family practice in Turkey.
AB  - The national project 'Transformation in Health' was started in 2005 to provide
      expert primary care by family physicians, and decrease expenses in Turkey. The
      number of family physicians was far below the need, so public physicians were
      promoted to family physician status after a 10-day intensive course. The
      government declared some satisfactory results, but privately paid family
      physicians were not accepted into the system. Furthermore, the government stopped
      paying for their services from private settings. Some family physicians became
      unemployed as the major payer for all forms of medical care in Turkey denied
      their services. The process showed it's value in time. Nevertheless, family
      physicians should be the core of this transformation as family medicine is an
      academic and a scientific discipline and a primary care-oriented specialty with
      its own specific educational content, research and base of evidence, which cannot
      be achieved through standard medical education. 

PMID- 24682841
TI  - Extra-corporeal membrane oxygenation for the post-cardiotomy patient.
AB  - Extra-corporeal membrane oxygenation remains the last resort in keeping patients
      alive in those with profound cardiogenic shock following percutaneous
      interventions or open surgery on the heart. No guidelines exist on the management
      of patients on such a device despite a high mortality. We attempt to highlight
      some universal principles that would be relevant to the current practice of those
      exposed to this challenging field. 

PMID- 24682842
TI  - Treatment of aortic stenosis with a self-expanding transcatheter valve: the
      International Multi-centre ADVANCE Study.
AB  - AIM: Transcatheter aortic valve implantation has become an alternative to surgery
      in higher risk patients with symptomatic aortic stenosis. The aim of the ADVANCE
      study was to evaluate outcomes following implantation of a self-expanding
      transcatheter aortic valve system in a fully monitored, multi-centre 'real-world'
      patient population in highly experienced centres. METHODS AND RESULTS: Patients
      with severe aortic stenosis at a higher surgical risk in whom implantation of the
      CoreValve System was decided by the Heart Team were included. Endpoints were a
      composite of major adverse cardiovascular and cerebrovascular events (MACCE; all
      cause mortality, myocardial infarction, stroke, or reintervention) and mortality
      at 30 days and 1 year. Endpoint-related events were independently adjudicated
      based on Valve Academic Research Consortium definitions. A total of 1015 patients
      [mean logistic EuroSCORE 19.4 +/- 12.3% [median (Q1,Q3), 16.0% (10.3, 25.3%)],
      age 81 +/- 6 years] were enrolled. Implantation of the CoreValve System led to a
      significant improvement in haemodynamics and an increase in the effective aortic
      valve orifice area. At 30 days, the MACCE rate was 8.0% (95% CI: 6.3-9.7%), all
      cause mortality was 4.5% (3.2-5.8%), cardiovascular mortality was 3.4% (2.3
      4.6%), and the rate of stroke was 3.0% (2.0-4.1%). The life-threatening or
      disabling bleeding rate was 4.0% (2.8-6.3%). The 12-month rates of MACCE, all
      cause mortality, cardiovascular mortality, and stroke were 21.2% (18.4-24.1%),
      17.9% (15.2-20.5%), 11.7% (9.4-14.1%), and 4.5% (2.9-6.1%), respectively. The 12
      month rates of all-cause mortality were 11.1, 16.5, and 23.6% among patients with
      a logistic EuroSCORE <=10%, EuroSCORE 10-20%, and EuroSCORE >20% (P< 0.05),
      respectively. CONCLUSION: The ADVANCE study demonstrates the safety and
      effectiveness of the CoreValve System with low mortality and stroke rates in
      higher risk real-world patients with severe aortic stenosis.

PMID- 24682843
TI  - Coronary artery disease severity and aortic stenosis: clinical outcomes according
      to SYNTAX score in patients undergoing transcatheter aortic valve implantation.
AB  - AIM: The aim of this study was to evaluate whether coronary artery disease (CAD)
      severity exerts a gradient of risk in patients with aortic stenosis (AS)
      undergoing transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: A
      total of 445 patients with severe AS undergoing TAVI were included into a
      prospective registry between 2007 and 2012. The preoperative SYNTAX score (SS)
      was determined from baseline coronary angiograms. In case of revascularization
      prior to TAVI, residual SS (rSS) was also determined. Clinical outcomes were
      compared between patients without CAD (n = 158), patients with low SS (0-22, n =
      207), and patients with high SS (SS > 22, n = 80). The pre-specified primary
      endpoint was the composite of cardiovascular death, stroke, or myocardial
      infarction (MI). At 1 year, CAD severity was associated with higher rates of the
      primary endpoint (no CAD: 12.5%, low SS: 16.1%, high SS: 29.6%; P = 0.016). This
      was driven by differences in cardiovascular mortality (no CAD: 8.6%, low SS:
      13.6%, high SS: 20.4%; P = 0.029), whereas the risk of stroke (no CAD: 5.1%, low
      SS: 3.3%, high SS: 6.7%; P = 0.79) and MI (no CAD: 1.5%, low SS: 1.1%, high SS:
      4.0%; P = 0.54) was similar across the three groups. Patients with high SS
      received less complete revascularization as indicated by a higher rSS (21.2 +/-
      12.0 vs. 4.0 +/- 4.4, P < 0.001) compared with patients with low SS. High rSS
      tertile (> 14) was associated with higher rates of the primary endpoint at 1 year
      (no CAD:12.5%, low rSS: 16.5%, high rSS: 26.3%, P = 0.043). CONCLUSIONS: Severity
      of CAD appears to be associated with impaired clinical outcomes at 1 year after
      TAVI. Patients with SS > 22 receive less complete revascularization and have a
      higher risk of cardiovascular death, stroke, or MI than patients without CAD or
      low SS.

PMID- 24682844
TI  - The efficacy of ticagrelor is maintained in women with acute coronary syndromes
      participating in the prospective, randomized, PLATelet inhibition and patient
      Outcomes (PLATO) trial.
AB  - AIMS: The aim of this study was to assess the relationship between sex and
      clinical outcomes and treatment-related complications in patients with ST
      elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to
      treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient
      Outcomes (PLATO) trial. METHODS: The associations between sex subgroup and the
      primary composite outcomes, secondary outcomes, and major bleeding endpoints as
      well as interaction of sex subgroup with treatment effects were analysed using
      Cox proportional-hazards models. RESULTS: Sex was not significantly associated
      with the probability of the primary composite endpoint [adjusted hazard ratio
      (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor
      was similarly more effective than clopidogrel in reducing rates of the primary
      endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs.
      11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death
      in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7%
      [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent
      thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs.
      2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments
      did not differ for PLATO-defined overall major bleeding complications in women
      [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had
      no significant association with these outcomes (interactions P = 0.43-0.88).
      CONCLUSION: Female sex is not an independent risk factor for adverse clinical
      outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy
      and safety profile in men and women.

PMID- 24682845
TI  - Streptococcus dysgalactiae subsp. equisimilis bacteremia: an emerging infection.
AB  - The importance of group C and G Streptococcus dysgalactiae subspecies equisimilis
      (S. dysgalactiae subsp. equisimilis) as a significant pathogen has recently been
      better recognized. S. dysgalactiae subsp. equisimilis disease can range in
      severity from milder skin and soft-tissue conditions such as wound infection,
      erysipelas, and cellulitis, to life-threatening necrotizing fasciitis and
      streptococcal toxic shock syndrome, thus sharing the clinical picture with S.
      pyogenes. The most common clinical manifestation of bacteremia is cellulitis. An
      increase in the incidence of S. dysgalactiae subsp. equisimilis bacteremia has
      been recognized. Invasive forms of this infection are most commonly found in
      elderly patients with underlying comorbidities and skin breakdown. The case
      fatality in bacteremia has been reported to be 15-18%. In this review, the
      epidemiology, clinical characteristics, and emm types of S. dysgalactiae subsp.
      equisimilis bacteremia are summarized.

PMID- 24682847
TI  - Ethmoidal dural arteriovenous fistula with unusual drainage route treated by
      transarterial embolization.
AB  - Ethmoidal dural arteriovenous fistulas (AVFs) are rare intracranial lesions
      associated with a high risk of intracranial hemorrhage. In particular, this
      entity with reflux drainage directly into the ophthalmic vein is extremely rare.
      We report a case of ethmoidal dural AVF with direct drainage of the superior
      ophthalmic vein (SOV) and inferior ophthalmic vein (IOV), successfully treated by
      endovascular surgery. A 58-year-old man presented with progressive diplopia.
      Angiography and contrast-enhanced CT showed an ethmoidal dural AVF supplied via
      the bilateral anterior ethmoidal arteries and venous drainage through the left
      SOV and IOV. A transarterial approach through the bilateral anterior ethmoidal
      arteries was used to place the microcatheter close to the fistula site. After
      intra-arterial embolization with 20% N-butyl cyanoacrylate, the dural AVF was
      completely occluded. In patients with good vascular access, endovascular
      transarterial embolization may be an effective and less invasive treatment
      strategy for ethmoidal dural AVF. 

PMID- 24682846
TI  - Sentinel lymph node dissection combined with meticulous histology increases the
      detection rate of nodal metastases in prostate cancer.
AB  - PURPOSE: To evaluate benefits of sentinel lymph node (SLN) biopsy for staging
      accuracy in prostate cancer. Extended pelvic lymph node dissection (ePLND) is a
      preferred staging tool; however, it may underestimate the incidence of nodal
      involvement. METHODS: Eighty patients with estimated risk of lymphadenopathy
      above 5 % based on Briganti nomogram had Tc-99m-labeled nanocolloid injected into
      the prostate. Planar lymphoscintigraphy and single-photon emission computed
      tomography/CT were performed to localize SLNs. Radioguided SLN dissection was
      followed by backup ePLND comprising external iliac, obturator and internal iliac
      regions. All SLNs were serially sectioned every 150 MUm and examined using
      hematoxylin and eosin; immunohistochemical staining was applied every 300 MUm.
      RESULTS: A total of 335 SLNs were detected, and 17 % were located outside ePLND
      template. Nodal metastases were diagnosed in 32 patients (40 %). Without
      radioguided SLN localization, solitary metastases posteriorly to the branches of
      the internal ilaic vessels, in pararectal and common iliac regions would not have
      been removed in five of 32 patients (16 %). Using standard histology protocol, we
      would have diagnosed metastases in 23 patients with median size of 2.8 mm. Serial
      sectioning of SLN and immunohistochemistry led to the detection of metastases in
      additional nine patients (28 %) with median size of 0.2 mm. CONCLUSION: ePLND
      comprised 83 % of SLNs, at least one SLN laid outside its template in 28 % of
      patients. ePLND and SLN dissection combined with nodal serial sectioning and
      immunohistochemistry increased the detection rate of nodal metastases by 68 % in
      comparison with ePLND alone and standard histology protocol.

PMID- 24682848
TI  - Factors affecting linkage to care and engagement in care for newly diagnosed HIV
      positive adolescents within fifteen adolescent medicine clinics in the United
      States.
AB  - Early linkage to care and engagement in care are critical for initiation of
      medical interventions. However, over 50 % of newly diagnosed persons do not
      receive HIV-related care within 6 months of diagnosis. We evaluated a linkage to
      care and engagement in care initiative for HIV-positive adolescents in 15 U.S.
      based clinics. Structural and client-level factors (e.g. demographic and
      behavioral characteristics, clinic staff and location) were evaluated as
      predictors of successful linkage and engagement. Within 32 months, 1,172/1,679
      (69.8 %) of adolescents were linked to care of which 1,043/1,172 (89 %) were
      engaged in care. Only 62.1 % (1,043/1,679) of adolescents were linked and engaged
      in care. Linkage to care failure was attributed to adolescent, provider, and
      clinic-specific factors. Many adolescents provided incomplete data during the
      linkage process or failed to attend appointments, both associated with failure to
      linkage to care. Additional improvements in HIV care will require creative
      approaches to coordinated data sharing, as well as continued outreach services to
      support newly diagnosed adolescents.

PMID- 24682851
TI  - Resonance assignment of the ribosome binding domain of E. coli ribosomal protein
      S1.
AB  - Ribosomal protein S1 is an essential actor for protein synthesis in Escherichia
      coli. It is involved in mRNA recruitment by the 30S ribosomal subunit and
      recognition of the correct start codon during translation initiation. E. coli S1
      is a modular protein that contains six repeats of an S1 motif, which have
      distinct functions despite structural homology. Whereas the three central repeats
      have been shown to be involved in mRNA recognition, the two first repeats that
      constitute the N-terminal domain of S1 are responsible for binding to the 30S
      subunit. Here we report the almost complete (1)H, (13)C and (15)N resonance
      assignment of two fragments of the 30S binding region of S1. The first fragment
      comprises only the first repeat. The second corresponds to the entire ribosome
      binding domain. Since S1 is absent from all high resolution X-ray structures of
      prokaryotic ribosomes, these data provide a first step towards atomic level
      structural characterization of this domain by NMR. Chemical shift analysis of the
      first repeat provides evidence for structural divergence from the canonical OB
      fold of an S1 motif. In contrast the second domain displays the expected topology
      for an S1 motif, which rationalizes the functional specialization of the two
      subdomains. 

PMID- 24682852
TI  - Anaesthetic EEG signal denoise using improved nonlocal mean methods.
AB  - This paper applies the nonlocal mean (NLM) method to denoise the simulated and
      real electroencephalograph signals. As a patch-based method, the NLM method
      calculates the weighted sum of a patch. The weight of each point is determined by
      the similarity between the points of the own patch and its neighbor. Based on the
      weighted sum, the noise is filtered out. In this study, the NLM denoising method
      is applied to signals with additive Gaussian white noise, spiking noise and
      specific frequency noise and the results are compared with that of the popular
      sym8 and db16 Wavelet threshold denoising (WTD) methods. The outcomes show that
      the NLM on average achieves 2.70 dB increase in improved signal to noise ratio
      (SNRimp) and 0.37 % drop in improved percentage distortion ratio compared with
      WTD. The moving adaptive shape patches-NLM performs better than the original NLM
      when the signals change dramatically. In addition, the performance of combined
      NLMWTD denoising method is also better than original WTD method (0.50-4.89 dB
      higher in SNRimp), especially, when the signal quality is poor.

PMID- 24682849
TI  - Relationship of vascular wall tension and autoregulation following traumatic
      brain injury.
AB  - BACKGROUND: The vascular wall tension (WT) of small cerebral vessels can be
      quantitatively estimated through the concept of critical closing pressure (CrCP),
      which denotes the lower limit of arterial blood pressure (ABP), below which small
      cerebral arterial vessels collapse and blood flow ceases. WT can be expressed as
      the difference between CrCP and intracranial pressure (ICP) and represent active
      vasomotor tone. In this study, we investigated the association of WT and CrCP
      with autoregulation and outcome of a large group of patients after traumatic
      brain injury (TBI). METHODS: We retrospectively analysed recordings of ABP, ICP
      and transcranial Doppler (TCD) blood flow velocity from 280 TBI patients (median
      age: 29 years; interquartile range: 20-43). CrCP and WT were calculated using the
      cerebrovascular impedance methodology. Autoregulation was assessed based on TCD
      based indices, Mx and ARI. RESULTS: Low values of WT were found to be associated
      with an impaired autoregulatory capacity, signified by its correlation to FV
      based indices Mx (R = -0.138; p = 0.021) and ARI (R = 0.118; p = 0.048). No
      relationship could be established between CrCP and any of the autoregulatory
      indices. Neither CrCP nor WT was found to correlate with outcome. CONCLUSIONS:
      Impaired autoregulation was found to be associated with a lower WT supporting the
      role of vasoparalysis in the loss of autoregulatory capacity. In contrast, no
      links between CrCP and autoregulation could be identified.

PMID- 24682853
TI  - Bone morphogenic protein-7 contributes to cerebral ischemic preconditioning
      induced-ischemic tolerance by activating p38 mitogen-activated protein kinase
      signaling pathway.
AB  - Cerebral ischemic preconditioning (IPC), which refers to a transient and
      noninjurious ischemia is able to induce tolerance against the subsequent lethal
      ischemia, including ischemic stroke. We have previously reported that bone
      morphogenic protein-7 (BMP-7) contributes to the neuroprotective effects of IPC
      induced ischemic tolerance, and thus ameliorates the following
      ischemia/reperfusion (I/R) injury in rats. Consequently, in the present study, we
      continued to explore the underlying regulatory mechanisms involved in BMP-7
      mediated cerebral IPC in the rat model of ischemic tolerance. Male Wistar rats
      were preconditioned by 15-min middle cerebral artery occlusion (MCAO). After 2
      day reperfusion, these animals were subjected to prolonged MCAO for 2 h. Our
      results showed that the phosphorylated p38 mitogen-activated protein kinase
      (MAPK) paralleling to BMP-7 was up-regulated by IPC in rat brain. Inactivation of
      p38 MAPK by pretreatment of SB203580, a p38 MAPK-specific suppressor, weakened
      the protective effect of IPC on CA1 neurons. Moreover, the enhanced
      phosphorylation of p38 MAPK induced by IPC was attenuated when the endogenous BMP
      7 was inhibited by BMP-7 antagonist noggin. Besides, blockade of p38 MAPK signal
      transduction pathway via SB203580 abrogated the protective effects of exogenous
      BMP-7 against cerebral infraction. These present findings suggest that BMP-7
      contributes to cerebral IPC-induced ischemic tolerance via activating p38 MAPK
      signaling pathway. 

PMID- 24682854
TI  - Naturally occurring alkaline amino acids function as efficient catalysts on
      Knoevenagel condensation at physiological pH: a mechanistic elucidation.
AB  - To maintain biological functions, thousands of different reactions take place in
      human body at physiological pH (7.0) and mild conditions, which is associated
      with health and disease. Therefore, to examine the catalytic function of the
      intrinsically occurring molecules, such as amino acids at neutral pH, is of
      fundamental interests. Natural basic alpha-amino acid of L-lysine, L-arginine,
      and L-histidine neutralized to physiological pH as salts were investigated for
      their ability to catalyze Knoevenagel condensation of benzaldehyde and ethyl
      cyanoacetate. Compared with their free base forms, although neutralized alkaline
      amino acid salts reduced the catalytic activity markedly, they were still capable
      to perform an efficient catalysis at physiological pH as porcine pancreatic
      lipase (PPL), one of the best enzymes that catalyze Knoevenagel condensation. In
      agreement with the fact that the three basic amino acids were well neutralized,
      stronger basic amino acid Arg and Lys showed more obvious variation in NH bend
      peak from the FTIR spectroscopy study. Study of ethanol/water system and
      quantitative kinetic analysis suggested that the microenvironment in the vicinity
      of amino acid salts and protonability/deprotonability of the amine moiety may
      determine their catalytic activity and mechanism. The kinetic study of best
      approximation suggested that the random binding might be the most probable
      catalytic mechanism for the neutralized alkaline amino acid salt-catalyzed
      Knoevenagel condensation. 

PMID- 24682855
TI  - Pulse pressure variability during hemorrhage and reinfusion in piglets: effects
      of age and tidal volume.
AB  - PURPOSE: The dynamic change in arterial pulse pressure during mechanical
      ventilation (PPV) predicts fluid responsiveness in adults but may not be
      applicable to pediatric patients. We compared PPV during hemorrhage and
      reinfusion in immature vs mature piglets at two clinically relevant tidal volumes
      (VT). METHODS: Following Institutional Animal Care Committee approval, we
      measured hemodynamics and PPV in two groups of piglets, 10-15 kg (immature, n =
      9) and 25-30 kg (mature, n = 10), under stable intravenous anesthesia at VT = 8
      and 10 mL.kg(-1). Measurements were taken at baseline, with blood withdrawal in 5
      mL.kg(-1) steps up to 30 mL.kg(-1), and during stepwise reinfusion. For each age
      group and VT, we constructed receiver operating characteristic (ROC) curves to
      determine the threshold value that was predictive of fluid responsiveness.
      RESULTS: Pulse pressure variability was significantly lower in immature vs mature
      pigs and at VT 8 vs VT 10 at every measurement period. The difference in PPV
      induced by changing VT was less in immature animals. Significant areas under the
      ROC curve were obtained in immature pigs at both VTs but in mature animals at VT
      10 alone. A PPV threshold was calculated to be 8.2% at VT 8 and 10.9% at VT 10 in
      immature animals vs 15.9% at VT 10 in mature animals, but sensitivity and
      specificity were only 0.7. CONCLUSION: Pulse pressure variability values are
      lower and less sensitive to VT in immature vs mature pigs. Adult PPV thresholds
      do not apply to pediatric patients, and a single PPV value representing fluid
      responsiveness should not be assumed.

PMID- 24682856
TI  - From the journal archives: Practical applicability of the epidural electrical
      stimulation test.

PMID- 24682857
TI  - High-level production of Fc-fused kringle domain in Pichia pastoris.
AB  - Recently, as a new non-immunoglobulin-based protein scaffold, a human kringle
      domain was successfully engineered toward biologically functional agonists and
      antagonists. In this study, the fed-batch cultivation conditions were optimized
      for enhanced production of an Fc-fused kringle domain (KD548-Fc) in Pichia
      pastoris. Fed-batch cultivations were performed in 5-l laboratory-scale
      bioreactors, and in order to find the optimal conditions for high-level
      production of KD548-Fc, several parameters including the initial carbon source
      (glycerol) concentration, temperature, and pH were investigated. When cells were
      cultivated at pH 4.0 and 25  degrees C with 9.5 % glycerol in the initial medium,
      the highest production yield (635 mg/l) was achieved with high productivity (7.2
      mg/l/h). Furthermore, functional KD548-Fc was successfully purified from the
      culture broth using a simple purification procedure with high purity and recovery
      yield.

PMID- 24682858
TI  - FLT3 inhibitors in AML: are we there yet?
AB  - FMS-like tyrosine kinase 3 (FLT3) is the most frequently mutated gene in AML.
      Thirty percent of patients with acute myeloid leukemia (AML) harbor activating
      mutations in FLT3, either internal tandem duplication mutations in the
      juxtamembrane domain (FLT3-ITD) or point mutations in the tyrosine kinase domain
      (FLT3 TKD). Small molecule FLT3 inhibitors have emerged as an attractive
      therapeutic option in patients with FLT3 mutations; however, the clinical
      activity of early inhibitors was limited by a lack of selectivity, potency and
      unfavorable pharmacokinetic properties. Newer agents such as quizartinib have
      improved potency and selectivity associated with much higher bone marrow response
      rates; however, response duration is limited by the development of secondary
      resistance. We will review here a number of FLT3 inhibitors that have been
      evaluated in clinical trials and discuss challenges facing the use of these
      agents in AML. 

PMID- 24682860
TI  - The other face of the moon: sense and sensibility in clinical practice.

PMID- 24682859
TI  - Pediatric-like therapy for adults with ALL.
AB  - Ten years ago, the first studies comparing the results of adult versus pediatric
      protocols in adolescents with acute lymphoblastic leukemia (ALL) clearly showed
      that differences in ALL genetics and treatment tolerance could not be the only
      reasons for the worse outcome observed in adults with this disease as compared to
      children. It became evident that intensified pediatric chemotherapy regimens
      could be associated with better response rates and longer survival in adults as
      well. During the last decade, the use of pediatric-like or pediatric-inspired
      protocols in adults allowed markedly improving the outcome of young adult
      patients aged up from 40 years to 60 years, confirming this initial observation.
      Administration of pediatric-like therapy in adults is now associated with
      estimated 5-year overall survival comprised between 60 % and 70 %. In this new
      context, the risk factors and the place of stem cell transplantation need to be
      reassessed. 

PMID- 24682863
TI  - Rare cause of adult female incontinence: complete duplication of the collecting
      system and ectopic ureter of the kidney draining into the vagina treated by
      laparoscopic upper pole heminephrectomy and ureterectomy.
AB  - A 38-year-old woman presented with a lifelong history of involuntary urinary
      leakage. The patient reported that she had been operated for her urinary leakage
      with the diagnosis of stress incontinence with transobturator tape two times at
      two different institutions. Preoperative computed tomography scan showed complete
      duplication of the left kidney with poorly functioning upper pole and a tortuous
      left dilated ureter running down and opening into the vagina. Laparoscopic left
      upper pole heminephrectomy and ureterectomy were performed uneventfully. Her
      incontinence improved immediately after surgery. 

PMID- 24682861
TI  - Use of HIV and HSV-2 biomarkers in sub-saharan adolescent prevention research: a
      comparison of two approaches.
AB  - Self-report of sexual behavior among adolescents is notoriously inconsistent, yet
      such measures are commonly used as outcomes for human immunodeficiency virus
      (HIV) prevention intervention trials. There has been a growing interest in the
      use of HIV and other sexually transmitted disease biomarkers as more valid
      measures of intervention impact in high HIV prevalence areas, particularly in sub
      Saharan Africa. We examine the challenges, benefits, and feasibility of including
      HIV and herpes simplex virus type 2 (HSV-2) biomarker data, with details about
      different data collection and disclosure methods from two adolescent prevention
      trials in Kenya and Zimbabwe. In Kenya, whole blood samples were collected using
      venipuncture; adult guardians were present during biomarker procedures and test
      results were disclosed to participants and their guardians. In contrast, in
      Zimbabwe, samples were collected using finger pricks for dried blood spots (DBS);
      guardians were not present during biomarker procedures, and results were not
      disclosed to participants and/or their guardians. In both countries, prevalence
      in the study samples was low. Although the standard of care for testing for HIV
      and other sexually transmitted infections includes disclosure in the presence of
      a guardian for adolescents under age 18, we conclude that more research about the
      risks and benefits of disclosure to adolescents in the context of a clinical
      trial is needed. Notably, current serological diagnosis for HSV-2 has a low
      positive predictive value when prevalence is low, resulting in an unacceptable
      proportion of false positives and serious concerns about disclosing test results
      to adolescents within a trial. We also conclude that the DBS approach is more
      convenient and efficient than venipuncture for field research, although both
      approaches are feasible. Manufacturer validation studies using DBS for HSV-2,
      however, are needed for widespread use. 

PMID- 24682862
TI  - Association between the growth rate of renal cysts/angiomyolipomas and age in the
      patients with tuberous sclerosis complex.
AB  - PURPOSE: Renal manifestations of tuberous sclerosis complex (TSC) occur with a
      high frequency and a wide range of severity. The onset and complications of each
      affected organ depend on the age. This study aimed to investigate the
      associations between comorbidities, frequency, and size of cysts/angiomyolipomas
      of TSC and the patients in the different ages. METHODS: We performed a systematic
      evaluation of patients with TSC at integrated clinics for TSC. The patients were
      diagnosed with TSC according to Roach's clinical diagnostic criteria. All the
      patients underwent a systematic evaluation with a medical history review,
      recording of cutaneous manifestations, magnetic resonance imaging of the brain,
      chest computed tomography scan, and cardiac echography. Each patient was
      routinely evaluated with renal magnetic resonance imaging. RESULTS: Of the 57
      patients with TSC, renal lesions or manifestations were observed in 38.5 % at
      preschool-age group (<6 years) that increased to 75.0, 85.7, and 100 % in school
      age group (6-18 years), young adulthood group (18-30 years), and middle-aged
      group >30 years, respectively. Renal complications or interventions were found in
      72.7 % of patients >30 years. There was a strongly positive association between
      the size of renal lesions and age (p < 0.001). Comorbidities of TSC were
      significantly correlated with pulmonary lymphangiomyomatosis (p < 0.001) and
      seizure remission (p = 0.018). CONCLUSIONS: The results indicate a positive
      association of progressively growing renal lesions in patients with TSC with
      increasing age. It is mandatory for clinicians that monitor the high-risk
      patients to minimize and prevent renal complications in the future.

PMID- 24682864
TI  - Epithelioid haemangioma: a rare cause of painful erections and sleep deprivation.
AB  - Epithelioid haemangioma of the penis is a rare condition which usually presents a
      solid single nodule. We report a case in a 43-year-old man who presented with
      painful erections and sleep disturbance with two palpable penile nodules.
      Magnetic resonance imaging with an artificially induced erection revealed these
      as individual lesions, and local excision was successfully undertaken.
      Pathological diagnosis of epithelioid haemangioma was confirmed with positive
      staining for CD31. Although rare, penile epithelioid haemangioma should be
      considered as a differential in an atypical penile mass. Induction in of an
      artificial erection prior to MRI can aid diagnosis and treatment is typically
      with surgical excision.

PMID- 24682865
TI  - Scalp eschar and neck lymphadenopathy after tick bite: an emerging syndrome with
      multiple causes.
AB  - The clinical and epidemiological features of 56 patients with scalp eschar
      associated with neck lymphadenopathy after a tick bite (SENLAT) syndrome were
      evaluated at the National French Rickettsial Center. Eschar swabs, crusts, and
      biopsies as well as ticks and blood samples were acquired for molecular and
      serological assays. SENLAT predominantly affects children (p < 0.05), followed by
      40- to 70-year-olds, and it is found mostly in women (p < 0.05). The seasonal
      distribution has two peaks: one in the spring (55%) and one in the autumn (30%).
      The etiological agent was identified in 18 cases, which include Rickettsia
      slovaca in 13 cases with incidences of two co-infections with Rickettsia raoultii
      and one case caused by Rickettsia sibirica mongolitimonae. Other possible agents
      that were found in attached ticks were Candidatus R. rioja, Coxiella burnetii,
      and Borrelia burgdorferi. The tick vector was Dermacentor marginatus in almost
      all cases, with the exception of one case, in which Ixodes ricinus was identified
      as the vector. Our findings show that SENLAT is a clinical entity characterized
      as a local infection controlled by the immune system and is neither pathogen- nor
      vector-specific. 

PMID- 24682866
TI  - Use of geosocial networking (GSN) mobile phone applications to find men for sex
      by men who have sex with men (MSM) in Washington, DC.
AB  - Current advances have added geosocial networking (GSN) mobile phone applications
      as an option for men who have sex with men (MSM) to meet other men. This is the
      first study to assess GSN application use and sex-seeking behaviors of MSM
      recruited using venue-based sampling. Among the 379 MSM in this study, 63.6 %
      reported using GSN applications to find men in the past year. Nearly one-quarter
      of MSM had sex with a man met using a GSN application in the prior year; these
      men were more likely to be under 35 years old and have had sex with a man met on
      the Internet; they were also less likely to be HIV-positive and have <5 male sex
      partners in the last year. GSN applications are a viable option for use in
      sampling and delivering interventions to young MSM who are often missed through
      other methods. 

PMID- 24682868
TI  - Acute airway obstruction secondary to vocal fold heterotopic ossification.
AB  - A 29-year old man of Eritrean origin presented with acute stridor and respiratory
      distress on a background 1 year history of progressive breathing difficulty and
      worsening inspiratory stridor. Fibreoptic laryngoscopy revealed an indeterminate
      swelling of the left vocal fold leaving no clear airway visible. The patient
      refused surgical tracheostomy. Microlaryngoscopy revealed a hard, calcified mass
      arising from the left cord preventing intubation. Histological analysis after
      excision revealed features consistent with heterotopic ossification. At 4 months
      repeat microlaryngoscopy was performed revealing normal appearance of the larynx
      and subglottis. Heterotopic ossification in the larynx is a very rare condition
      that presents a diagnostic and therapeutic challenge. In the first documented
      case in the larynx, we describe how the disease caused life threatening airway
      obstruction, but was managed in a way that led to preservation of laryngeal
      function and complete resolution of the condition.

PMID- 24682867
TI  - Rectal versus non-rectal primary signet ring cell carcinoma of the colorectum: a
      retrospective survival analysis controlled for confounders.
AB  - PURPOSE: Our objective was to compare the outcomes of rectal and non-rectal
      primary signet ring cell adenocarcinoma of the colorectum. METHODS: A
      retrospective survival analysis was performed using the Surveillance,
      Epidemiology, and End Results Program database between 2004 and 2009 on subjects
      who were diagnosed as having a primary signet ring cell carcinoma of the
      colorectum. Cox proportional hazard regression analysis controlled for
      confounders was used to assess overall survival comparing rectal and non-rectal
      cancers. RESULTS: Our population was composed of 1,484 patients: 200 affected by
      rectal cancer and 1,284 by non-rectal cancer. Unadjusted survival curves resulted
      to be almost superimposable (P = 0.916). After controlling for age, gender, race,
      tumor stage, grade, and size, tumor location demonstrated a statistically
      significant impact on overall survival (P = 0.032; 95% confidence interval 0.640
      0.980; hazard ratio 0.792). CONCLUSION: On the basis of analysis of information
      from the SEER database, the signet ring cell carcinoma of the rectum was
      associated to a worse prognosis as compared to non-rectal cancer.

PMID- 24682869
TI  - Functional analysis of pyochelin-/enantiopyochelin-related genes from a
      pathogenicity island of Pseudomonas aeruginosa strain PA14.
AB  - Genomic islands are foreign DNA blocks inserted in so-called regions of genomic
      plasticity (RGP). Depending on their gene content, they are classified as
      pathogenicity, symbiosis, metabolic, fitness or resistance islands, although a
      detailed functional analysis is often lacking. Here we focused on a 34-kb
      pathogenicity island of Pseudomonas aeruginosa PA14 (PA14GI-6), which is inserted
      at RGP5 and carries genes related to those for pyochelin/enantiopyochelin
      biosynthesis. These enantiomeric siderophores of P. aeruginosa and certain
      strains of Pseudomonas protegens are assembled by a thiotemplate mechanism from
      salicylate and two molecules of cysteine. The biochemical function of several
      proteins encoded by PA14GI-6 was investigated by a series of complementation
      analyses using mutants affected in potential homologs. We found that PA14_54940
      codes for a bifunctional salicylate synthase/salicyl-AMP ligase (for generation
      and activation of salicylate), that PA14_54930 specifies a dihydroaeruginoic acid
      (Dha) synthetase (for coupling salicylate with a cysteine-derived thiazoline
      ring), that PA14_54910 produces a type II thioesterase (for quality control), and
      that PA14_54880 encodes a serine O-acetyltransferase (for increased cysteine
      availability). The structure of the PA14GI-6-specified metabolite was determined
      by mass spectrometry, thin-layer chromatography, and HPLC as (R)-Dha, an iron
      chelator with antibacterial, antifungal and antitumor activity. The conservation
      of this genomic island in many clinical and environmental P. aeruginosa isolates
      of different geographical origin suggests that the ability for Dha production may
      confer a selective advantage to its host. 

PMID- 24682870
TI  - Longer hospital stay after Fontan completion in the November to March period.
AB  - OBJECTIVES: Initial evidence suggests that total cavopulmonary connection (TCPC)
      completion during winter is associated with prolonged pleural effusion and
      hospitalization. This study was carried out to review the impact of season of
      operation on short-term outcome after TCPC procedure. METHODS: We conducted a
      retrospective study on 104 consecutive patients who underwent the extracardiac
      TCPC procedure from June 2006 to November 2011 (mean age 5.0 +/- 2.6 years, 60
      males). The outcomes of interest assessed were length of postoperative hospital
      stay (LOS) and duration of pleural drainage. These were adjusted to potential,
      known standard Fontan risk factors such as age, ventricular morphology, cardiac
      function and previous surgical history. Length of chest drainage and LOS in the
      period November-March (NM) was compared with that in the period April-October
      (AO). RESULTS: Of the 104 patients, 6 patients were excluded since they either
      required early reoperation or were transferred to another institution for their
      postoperative care. The group included 26 children with hypoplastic left heart
      syndrome. Thirty-four of the 98 remaining patients (34.7%) had surgery in the NM
      period. Overall, length of pleural drainage was 9 days (interquartile range 6-13)
      and LOS was 12 days (9-17). TCPC surgery in the NM period (P = 0.045), male
      gender (P = 0.020) and right ventricular morphology (P = 0.034) were the only
      variables associated with prolonged LOS at univariate analysis; no other factor
      including ventricular function, Glenn pressure, weight and age at operation were
      associated with LOS. NM surgery was the only predictor of LOS at multivariate
      analysis (P = 0.045). Patients with surgery in the NM period had a higher
      incidence of low cardiac output/acute renal dysfunction postoperatively (26.5 vs
      9.4%, P = 0.038) and a higher incidence of infections requiring antibiotic use
      (64.7 vs 32.8%, P = 0.003). CONCLUSIONS: TCPC surgery performed in the period
      between November and March is associated with increased morbidity, especially
      longer hospitalization. Given the elective nature of TCPC operation, this
      operation should be scheduled outside of the NM period if possible.

PMID- 24682871
TI  - Incidence, risk factors and clinical outcomes for acute kidney injury after
      aortic arch repair in paediatric patients.
AB  - OBJECTIVES: Acute kidney injury (AKI) is common after paediatric cardiac surgery
      and associated with increased morbidity and mortality. Aortic arch surgery may be
      an independent risk factor for AKI because of circulatory arrest below the
      descending thoracic artery during anastomosis. We investigated the surgical
      outcomes associated with AKI after aortic arch repair in paediatric patients.
      METHODS: We retrospectively analysed 120 paediatric patients who underwent aortic
      arch repair between 2003 and 2012. AKI was defined according to the paediatric
      modified risk, injury, failure, loss and end-stage kidney disease criteria. The
      incidence, clinical outcomes and risk factors for AKI were analysed. RESULTS:
      Aortic arch repair was performed for coarctation of aorta in 97 patients and
      interrupted aortic arch in 23 patients. The median age and body weight at the
      time of surgery were 16.5 days and 3.3 kg, respectively. The mean duration of the
      follow-up was 3.9 years. AKI developed in 42 patients (36.8%) and peritoneal
      dialysis (PD) was applied in 20 patients (16.7%). The recovery of renal function
      began a mean of 3.8 days after conservative management, and full recovery
      occurred a mean of 6.7 days after conservative management. A lower body weight
      (<3.0 kg) (odds ratio [OR]: 7.569, P = 0.009) and the absence of prerenal
      impairment (OR: 9.876, P = 0.041) were shown to be independent risk factors.
      Patients who required PD had prolonged intensive care unit and hospital stays (P
      = 0.002 and P = 0.003). CONCLUSIONS: AKI is common in low-birth-weight patients
      after aortic arch repair surgery. However, patients recover from AKI after
      conservative management. Requiring PD increases the morbidity associated with
      AKI.

PMID- 24682872
TI  - Resection of the stenotic segment with individually tailored anastomosis for
      symptomatic congenital tracheal stenosis in infants.
AB  - OBJECTIVES: To analyse retrospectively population-based results of congenital
      tracheal stenosis (CTS) repair in infants in Finland. METHODS: Data on infants
      who were operated on for CTS in Helsinki Children's Hospital between August 1988
      and May 2013 were analysed retrospectively. Fibreoptic bronchoscopy was performed
      perioperatively and in follow-up of all the surviving patients. The median follow
      up time was 7 (range 1-20) years. RESULTS: Thirteen infants were operated on for
      CTS. Resection of the stenotic segment with individually tailored anastomosis was
      used in 12 patients and slide tracheoplasty in 1 patient. The median age at the
      operation was 2.9 (range 0.2-19) months. Eight (62%) patients had associated
      cardiovascular defects, which were corrected during the same operation. The
      median length of stenosis was 35% (range 25-60%) of the total length of the
      trachea. The median length of time of postoperative mechanical ventilation was 10
      (range 5-19) days. The median length of time of intensive care treatment was 15
      (range 7-40) days. One patient died from hypoplastic lung tissue and fibrosis,
      and multiorgan failure. One patient required reoperation, and 3 other patients
      received balloon bronchodilatations postoperatively. There was no late mortality.
      All of the 12 survivors had a good outcome. CONCLUSION: Resection with
      individually tailored anastomosis with up to 55% of the stenotic segment of the
      trachea presented a good long-term outcome.

PMID- 24682873
TI  - Identification of potential serum biomarkers for rheumatoid arthritis by high
      resolution quantitative proteomic analysis.
AB  - The aim of this study was to find serum biomarkers of rheumatoid arthritis (RA)
      by high-resolution proteomic analysis. Low-abundance proteins from pooling serum
      sample of early RA patients and healthy controls were enriched using
      ProteoMinerTM enrichment kits. The enriched proteins were separated on SDS-PAGE,
      digested by trypsin, labeled with tandem mass tag (TMT) reagents, and desalted by
      C18 stage tip column. Then, the labeled peptides were analyzed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) with nano-LC combined with
      Orbitrap Q Exactive mass spectrometer, and experiments were carried out three
      times using different specimens, and differentially expressed proteins were
      screened by intensity ratios of identified peptides. Enzyme-linked immunosorbent
      assays (ELISAs) were performed to confirm differentially expressed proteins.
      Twenty-six proteins were found differentially expressed in RA serum by high
      resolution proteomic analysis. Among them, levels of thrombospondin-1, ficolin-2,
      isoform 10 of fibronectin, and apolipoprotein E were higher in RA patients than
      in healthy controls (RA/healthy control (HC) >= 1.5, p<0.05), while levels of
      angiotensinogen, paraoxonase/arylesterase 1, isoform E of proteoglycan 4, and
      plasminogen were significantly lower (RA/HC <= 0.67, p<0.05). Further study by
      ELISA showed a higher level of ficolin-2 in the serum of RA patients compared to
      healthy controls; the level of ficolin-2 was found to be positively correlated
      with swollen joint counts (SJCs), disease activity score (DAS28), rheumatoid
      factor, and IgM in RA patients and with DAS28 and IgM in early RA patients
      through statistical analysis. The results of this study suggest that ficolin-2,
      as a newly screened biomarker by high-resolution quantitative proteomic analysis,
      offers the potentiality to become a diagnostic or disease evaluation tool in RA.

PMID- 24682874
TI  - FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in
      a mouse model by impairing the motility of bone marrow-derived mesenchymal stem
      cells.
AB  - FTY720 is a novel immunosuppressant that modulates sphingosine 1-phosphate (S1P)
      receptors for the treatment of several diseases. Several hallmarks of liver
      fibrosis are influenced by S1P, and the interference of S1P signaling by
      treatment with FTY720 results in beneficial effects in various animal models of
      fibrosis. However, whether these treatment strategies suppress liver fibrosis
      progression is incompletely understood. Here, we investigated the effects and
      mechanisms by which FTY720 improves liver fibrosis in the carbon tetrachloride
      (CCl4)-induced mouse model. FTY720 treatment significantly attenuated the
      expression of fibrotic markers in the injured liver of both wild-type and SCID
      beige mice. The migration of bone marrow-derived mesenchymal stem cells (BMSCs)
      to circulation, and subsequently the injured liver, was suppressed by FTY720.
      Furthermore, in vitro, phosphorylated-FTY720 blocked the migration of BMSCs
      mediated by S1P. Thus, FTY720 is an effective therapy for liver fibrosis via the
      suppression of BMSC migration in the CCl4-induced mouse model. 

PMID- 24682875
TI  - Evaluation of the anaerobic co-digestion of sewage sludge and tomato waste at
      mesophilic temperature.
AB  - Sewage sludge is a hazardous waste, which must be managed adequately. Mesophilic
      anaerobic digestion is a widely employed treatment for sewage sludge involving
      several disadvantages such as low methane yield, poor biodegradability, and
      nutrient imbalance. Tomato waste was proposed as an easily biodegradable co
      substrate to increase the viability of the process in a centralized system. The
      mixture proportion of sewage sludge and tomato waste evaluated was 95:5 (wet
      weight), respectively. The stability was maintained within correct parameters in
      an organic loading rate from 0.4 to 2.2 kg total volatile solids (VS)/m(3) day.
      Moreover, the methane yield coefficient was 159 l/kg VS (0  degrees C, 1 atm),
      and the studied mixture showed a high anaerobic biodegradability of 95 % (in VS).
      Although the ammonia concentration increased until 1,864 +/- 23 mg/l, no
      inhibition phenomenon was determined in the stability variables, methane yield,
      or kinetics parameters studied.

PMID- 24682876
TI  - Structure and properties of bacterial cellulose produced using a trickling bed
      reactor.
AB  - Structure and properties of bacterial cellulose (BC) produced by trickling
      fermentation were studied. The following indexes, such as extrinsic shapes,
      microstructure, chemical structure, purity, water holding capacity, porosity, and
      thermogravimetric characteristics, are recommended for assessing the structure
      and properties of bacterial cellulose. With the comparison to bacterial cellulose
      produced by static fermentation and shaking fermentation, the results showed that
      for different BC cultivation methods, the extrinsic shapes, synthetic mode, and
      microstructure were different. The basic consistency of the infrared spectrogram
      from three kinds of bacterial cellulose reflected that the chemical structures
      were very similar. But the -OH associating degree of trickling fermentation BC
      was higher, and the polymerization degree, purity, water holding capacity,
      porosity, and thermal stability of trickling fermentation BC were also higher
      than those of static fermentation BC and shaking fermentation BC. But the
      crystallinity and crystal grain size of trickling fermentation BC were less than
      those of static fermentation BC and greater than those of shaking fermentation BC
      and plant fiber. These above structure and properties of trickling fermentation
      BC could reference bacterial cellulose's application in food and material field. 

PMID- 24682877
TI  - The characteristics of chitinase expression in Aeromonas schubertii.
AB  - In this study, chitinase activity in an incubation broth of Aeromonas schubertii
      was measured using colloidal chitin azure as the substrate. More specifically,
      the induction of chitinases due to amendment with various carbon sources was
      examined. The highest chitinase activity was found following amendment with 0.5
      1.0 % chitin powder, whereas the activity increased negligibly due to amendment
      with other carbon sources, such as glucose, GlcNAc, GlcN, sorbitol, sucrose,
      cellulose, or starch. The chitinase activity induced by the chitin powder was
      suppressed when the glucose, GlcNAc, GlcN, or starch was added simultaneously to
      the medium but was not suppressed by the addition of sorbitol, sucrose, or
      cellulose. The activity of chitinase in the crude extract was also not directly
      inhibited by glucose. Taken together, these findings suggest that the induction
      of chitinase activity depends on the acquisition of suitable carbon sources from
      the environment and that induction occurs at a regulatory level.

PMID- 24682878
TI  - Optimization of culture conditions for enhanced lysine production using
      engineered Escherichia coli.
AB  - In this study, culture conditions, including dissolved oxygen (DO) content,
      presence of osmoprotectants, residual glucose concentration, and ammonium sulfate
      feeding strategies, were investigated for decreasing the inhibition effects of
      acetic acid, ammonium, and osmotic stress on L-lysine fermentation by Escherichia
      coli. The results revealed that higher DO content and lower residual glucose
      concentration could decrease acetic acid accumulation, betaine supplementation
      could enhance osmotic stress tolerance, and variable speed ammonium sulfate
      feeding strategy could decrease ammonium inhibition. Thus, with 25 % DO content,
      0-5.0 g/L of residual glucose concentration, and 1.5 g/L of betaine
      supplementation, 134.9 g/L of L-lysine was obtained after 72 h of culture, with L
      lysine yield and productivity of 45.4 % and 1.9 g/(L . h), respectively.

PMID- 24682879
TI  - Probiotic attributes of autochthonous Lactobacillus rhamnosus strains of human
      origin.
AB  - The study was aimed at evaluating the probiotic potential of indigenous
      autochthonous Lactobacillus rhamnosus strains isolated from infant feces and
      vaginal mucosa of healthy female. The survival of the selected strains and the
      two reference strains (L. rhamnosus GG and L. casei Actimel) was 67-81 % at pH 2
      and 70-80 % after passage through the simulated gastrointestinal fluid. These
      strains are able to grow in the presence of 4 % bile salt, 10 % NaCl, and 0.6 %
      phenol. The cell surface of L. rhamnosus strains is hydrophilic in nature as
      revealed by bacterial adhesion to hydrocarbons (BATH) assay. Despite this, L.
      rhamnosus strains showed mucin adherence, autoaggregation and coaggregation
      properties that are strain-specific. In addition, they produce bile salt
      hydrolase (BSH) and beta-galactosidase activities. L. rhamnosus strains exhibit
      antimicrobial activity against food spoilage organisms and gastrointestinal
      pathogens, as well as Candida and Aspergillus spp. L. rhamnosus strains have
      similar antibiotic susceptibility pattern, and resistance to certain antibiotics
      is intrinsic or innate. The strains are neither haemolytic nor producer of
      biogenic amines such as histamine, putrescine, cadaverine and tyramine.
      Lyophilized cells of L. rhamnosus Fb exhibited probiotic properties demonstrating
      potential of the strain for technological suitability and in the preparation of
      diverse probiotic food formulations. 

PMID- 24682880
TI  - Enhanced slow inactivation of the human skeletal muscle sodium channel causing
      normokalemic periodic paralysis.
AB  - Normokalemic periodic paralysis (normoPP) is a type of skeletal muscle function
      disorder which is characterized by paralysis attack with concomitant normal serum
      potassium level. We previously reported that R675Q mutation of human skeletal
      muscle voltage-gated sodium channel alpha subunit (SCN4A) may be the novel
      mutation which caused normoPP in Chinese families. However, it is still not clear
      how this mutation affects the SCN4A channel function. In this study, we used
      patch-clamp recording to study the function of wild type (WT) and R675Q mutant of
      SCN4A channels expressed in human embryonic kidney (HEK293) cells. We found that
      R675Q mutation did not affect the voltage dependence of sodium channel
      activation. The fast inactivation was also not significantly affected by R675Q
      mutation. However, R675Q mutation of SCN4A channels exhibited an 11.1 mV
      hyperpolarized shift in the voltage dependence of slow inactivation and
      significantly prolonged the recovery from prolonged inactivation state. Our
      results thus indicate that SCN4A was functionally affected by R675Q mutation,
      suggesting a possible reason for causing normoPP in Chinese patients.

PMID- 24682881
TI  - Immunomodulatory activity of two potential probiotic strains in LPS-stimulated HT
      29 cells.
AB  - The relative expression of mucin, pro- and anti-inflammatory genes besides other
      signaling molecules in HT-29 cells by two test probiotic strains of Lactobacillus
      plantarum Lp9 and Lp91 and the reference strain L. plantarum 5276 was evaluated
      by RT-qPCR using Relative Expression Software Tool qBase-Plus under in vitro
      simulated gut conditions. Ten house keeping genes were evaluated by using geNorm
      3.4 excel based application. The most stable genes were RPL27, ACTB and B2M which
      were subsequently used for calculating the normalization factor. Under
      pretreatment conditions (4 h probiotic treatment, followed by lipopolysaccharide
      challenge for 3 h), all the three strains evoked downregulation of IL-8
      expression by ~100 %, while in case of TNF-alpha, the downregulation of the
      relative gene expression was at the rate of 98.2, 93.8 and 98.0 % with Lp5276,
      Lp9 and Lp91, respectively, under the same set of conditions. Lp91 evoked maximum
      downregulation of IL12p35 and IFN-gamma with corresponding fold reduction in
      relative expression of the two genes by 96.5 and 96.7 % during pre-treatment
      conditions. However, IL-10 and IFN-alpha were significantly upregulated to the
      extent of 8.13 +/- 0.36 and 2.62 +/- 0.14 fold by Lp91 under the same conditions.
      Lp9 and Lp91 were also quite effective in inducing the expression of Cox-1 and
      Cox-2 in HT-29 cells as can be reflected from their ratios, i.e., 5.90 and 6.50
      (under pretreatment conditions); 3.79 and 4.36 (under co-culture conditions).
      Thus, the two putative indigenous L. plantarum strains Lp9 and Lp91 demonstrated
      immunomodulating functions in HT-29 cells at significant levels under different
      experimental conditions. 

PMID- 24682882
TI  - High frequency of rare variants with a moderate-to-high predicted biological
      effect in protocadherin genes of extremely obese.
AB  - Relatively rare variants with a moderate-to-high biological effect may contribute
      to the genetic predisposition of common disorders. To investigate this for
      obesity, we performed exome sequencing for 30 young (mean age: 29.7 years)
      extremely obese Caucasian subjects (mean body mass index: 51.1 kg/m(2); m/f =
      11/29). Rare variants with a moderate-to-high predicted biological effect were
      assembled and subjected to functional clustering analysis. It showed that the 55
      clustered protocadherin genes on chromosome 5q31 have a significantly (P = 0.002)
      higher frequency of rare variants than a set of 325 reference genes. Since the
      protocadherin genes are expressed in the hypothalamus, we tested another 167
      genes related to the function of the hypothalamus, but in those genes, the
      frequency of rare variants was not different from that of the reference genes. To
      verify the relation of variation in the protocadherin genes with extreme obesity,
      we analyzed data from more than 4,000 European Americans present on the Exome
      Variant Server, representing a sample of the general population. The significant
      enrichment of rare variants in the protocadherin genes was only observed with the
      group of extremely obese individuals but not in the "general population",
      indicating an association between rare variants in the protocadherin cluster
      genes and extreme obesity. 

PMID- 24682883
TI  - Flavonoids in modulation of cell survival signalling pathways.
AB  - Flavonoids, a family of polyphenols, generally found in various fruits and
      vegetables, as well as in many plant beverages such as tea, pomegranate juice,
      raspberry, blueberries, and red wine. Recently, studies on flavonoids have
      attracted scientific attention as a potential nutritional strategy to prevent a
      broad range of chronic disorders. Many studies suggest that consumption of these
      flavonoids in sufficient amount plays neuroprotective, cardioprotective, anti
      inflammatory, and chemopreventive roles. While there has been a major focus on
      the antioxidant properties, there is an emerging view that flavonoids and their
      in vivo metabolites do not act only as conventional antioxidants but may also
      exert modulatory actions on cellular system through direct action on various
      signalling pathways. These pathways include phosphoinositide 3-kinase,
      Akt/protein kinase B, mitogen-activated protein kinase, tyrosine kinases, and
      protein kinase C. Various inhibitory or stimulatory actions of flavonoids on
      these pathways greatly affect cellular functions by altering the phosphorylation
      state of targeted molecules. In addition, flavonoids also modulate various gene
      expressions through activation of various transcription factors. Thus, the
      present review will bestow a breathing overview regarding the prime role of
      flavonoids in modulation of survival signalling pathways at cellular system. 

PMID- 24682885
TI  - Angular change in the line of vision to the larynx: implications for determining
      the laryngoscopic view.
AB  - BACKGROUND: We measured the angular change from the line of vision to the larynx
      around the upper incisors under defined laryngoscopic forces and investigated its
      association with the laryngoscopic view. METHODS: Laryngoscopy was performed
      under general anesthesia with muscle paralysis in male patients with a difficult
      laryngoscopy (DLG, n = 11) and in male patients matched for age and body mass
      index with an easy laryngoscopy (ELG, n = 11). A Macintosh blade #3 was used for
      the procedure. The line of vision was marked on lateral photographs during
      laryngoscopy by simultaneously delineating two straight lines: a line from the
      upper incisors to the lowest surface of the laryngoscope blade and a line from
      the upper incisors to the thyroid notch. The angle difference, defined as the
      angle between those two lines, was measured at laryngoscopic forces of 10-50 N.
      RESULTS: The angle difference was significantly greater in the DLG than in the
      ELG at 50 N [median, 18.0 degrees  (range, 16.5-21.0 degrees ) vs 12.0 degrees 
      (12.0-13.5 degrees ), respectively; P < 0.001] and at lower forces (10-40 N; P <=
      0.001). A higher Cormack-Lehane grade was associated with a greater angle
      difference at 50 N (P < 0.001). CONCLUSIONS: Compared with ELG, DLG is associated
      with a larger angle difference, i.e., a larger gap between the underside of the
      blade and the thyroid notch at all laryngoscopic forces (10-50 N). The concept of
      angle difference, based on the angular change in the line of vision around the
      upper incisors, may provide a new approach to understanding DLG. This study was
      registered with the Clinical Research Information Service, registration number
      KCT0000433.

PMID- 24682884
TI  - Lessons learned from the International Renal Cell Carcinoma-Venous Thrombus
      Consortium (IRCC-VTC).
AB  - Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena
      cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range
      of different clinical and surgical scenarios, making natural history and
      oncological outcomes variable and poorly characterized. Infrequency and
      variability make it necessary to share the experience from different institutions
      to properly analyze surgical outcomes in this setting. The International Renal
      Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the
      questions generated by competing results from different retrospective studies in
      RCC with venous extension on current controversial topics. The aim of this
      article is to summarize the experience gained from the analysis of the world's
      largest cohort of patients in this unique setting to date.

PMID- 24682886
TI  - From the Journal archives: Improving patient outcomes in the era of big data.
      1992.

PMID- 24682887
TI  - Factors that influence physicians' and medical students' confidence in counseling
      patients about physical activity.
AB  - Less than half of US adults and two-thirds of US high school students do not meet
      current US guidelines for physical activity. We examined which factors promoted
      physicians' and medical students' confidence in counseling patients about
      physical activity. We established an online exercise survey targeting attending
      physicians, resident and fellow physicians, and medical students to determine
      their current level of physical activity and confidence in counseling patients
      about physical activity. We compared their personal level of physical activity
      with the 2008 Physical Activity Guidelines of the US Department of Health and
      Human Services (USDHHS). We administered a survey in 2009 and 2010 that used the
      short form of the International Physical Activity Questionnaire. A total of 1,949
      individuals responded to the survey, of whom 1,751 (i.e., 566 attending
      physicians, 138 fellow physicians, 806 resident physicians, and 215 medical
      students) were included in this analysis. After adjusting for their BMI, the odds
      that physicians and medical students who met USDHHS guidelines for vigorous
      activity would express confidence in their ability to provide exercise counseling
      were more than twice that of physicians who did not meet these guidelines.
      Individuals who were overweight were less likely to be confident than those with
      normal BMI, after adjusting for whether they met the vigorous exercise
      guidelines. Physicians with obesity were even less likely to express confidence
      in regards to exercise counseling. We conclude that physicians and medical
      students who had a normal BMI and met vigorous USDHHS guidelines were more likely
      to feel confident about counseling their patients about physical activity. Our
      findings suggest that graduate medical school education should focus on health
      promotion in their students, as this will likely lead to improved health
      behaviors in their students' patient populations. 

PMID- 24682888
TI  - MicroRNA expressions associated with eosinophilic meningitis caused by
      Angiostrongylus cantonensis infection in a mouse model.
AB  - Angiostrongylus cantonensis (A. cantonensis) infection is the major cause of
      eosinophilic meningitis (EM). Severe cases or infant and child cases have poor
      prognosis. MicroRNAs (miRNAs) play important roles in inflammation; however,
      little is known about the roles in brain inflammation caused by A. cantonensis.
      In this study, Illumina deep sequencing and bioinformatics were used to determine
      the abundance and differential expression of miRNAs in the brain tissues of a
      mouse model. A total of 648 conserved miRNAs were identified, 157 of which were
      significantly differentially expressed between infected mice and normal mice. The
      five most fold-changed miRNAs were miR-511-5p, miR-511-3p, miR-223-3p, miR-155-5p
      and miR-206-3p. These expressions of miR-511, miR-223, miR-155, miR-206, miR-142
      and miR-21a were validated by quantitative reverse transcription polymerase chain
      reaction (RT-PCR). The analysis of these miRNAs showed that miR-511-3p was more
      abundant than the miR-511-5p strand, and increased to a peak in 21 days after A.
      cantonensis infection, miR-223 might be a potential indicator of disease severity
      and the upregulation of miR-155-5p after stimulation with the somatic antigen of
      phase IV A. cantonensis implied its involvement in the central nervous system
      (CNS) inflammation induced by A. cantonensis infection. These observations
      suggest that miRNAs may play important roles in the regulation of EM caused by A.
      cantonensis infection.

PMID- 24682889
TI  - Mapping one strong 'Ohana: using network analysis and GIS to enhance the
      effectiveness of a statewide coalition to prevent child abuse and neglect.
AB  - Network analysis and GIS enable the presentation of meaningful data about
      organizational relationships and community characteristics, respectively.
      Together, these tools can provide a concrete representation of the ecological
      context in which coalitions operate, and may help coalitions identify
      opportunities for growth and enhanced effectiveness. This study uses network
      analysis and GIS mapping as part of an evaluation of the One Strong 'Ohana (OSO)
      campaign. The OSO campaign was launched in 2012 via a partnership between the
      Hawai'i Children's Trust Fund (HCTF) and the Joyful Heart Foundation. The OSO
      campaign uses a collaborative approach aimed at increasing public awareness of
      child maltreatment and protective factors that can prevent maltreatment, as well
      as enhancing the effectiveness of the HCTF Coalition. This study focuses on three
      elements of the OSO campaign evaluation: (1) Network analysis exploring the
      relationships between 24 active Coalition member organizations, (2) GIS mapping
      of responses to a randomized statewide phone survey (n = 1,450) assessing
      awareness of factors contributing to child maltreatment, and (3) Combined GIS
      maps and network data, illustrating opportunities for geographically-targeted
      coalition building and public awareness activities.

PMID- 24682890
TI  - Acute revascularization in ST-segment-elevation myocardial infarction.
AB  - We briefly and comprehensively present some of the novel findings in the field of
      revascularization therapy and management of ST-segment-elevation myocardial
      infarction (STEMI). We highlight the latest evidence-based advancements in the
      pharmacological and mechanical treatment of patients who presented with STEMI.
      Since the last updates to the international guidelines (American College of
      Cardiology/American Heart Association and the European Society of Cardiology)
      were published in 2011 and 2012, there have been changes and several important
      studies have presented their final outcomes. We also highlight some controversial
      approaches as part of the current debates in the cardiology community. In
      addition, we share our recent experience in the field of biodegradable scaffold
      stents as a treatment strategy in STEMI. 

PMID- 24682891
TI  - Hyperbaric area index calculated from ABPM elucidates the condition of CKD
      patients: the CKD-JAC study.
AB  - BACKGROUND: High prevalence of masked hypertension as well as persistent
      hypertension was observed in the Chronic Kidney Disease Japan Cohort (CKD-JAC)
      study. We proposed a novel indicator of blood pressure (BP) load, hyperbaric area
      index (HBI), calculated from ambulatory blood pressure monitoring (ABPM) data.
      The characteristic of this index and its relationship with kidney function were
      also evaluated. METHODS: The CKD-JAC study, enrolled 2,977 patients, is a
      prospective observational study started in September 2007. ABPM was conducted in
      a sub-group from September 2007 to April 2010 and baseline ABPM data of 1,075
      subjects (63.4 % male, 60.7 years old) were analyzed. RESULTS: Mean systolic HBI
      of male and female patients were 242.3 and 176.5 mmHg*h, respectively. HBI
      sensitively reflected sex (54.7 mmHg*h higher in males than in females), seasonal
      effects (51.6 mmHg*h higher in winter than in summer), and advancing CKD stage
      [(16.5 mmHg*h higher) per -10 mL/min/1.73 m(2) in eGFR]. The HBI was a
      significant factor to associate with reduced kidney function, after adjusting
      with nocturnal BP change (NBPC), sex, and other variables (p value <0.001).
      CONCLUSIONS: Our findings suggested that HBI might be a novel sensitive indicator
      for the reduction of kidney function, independent of patterns of NBPC.

PMID- 24682892
TI  - Down-regulated expression of acid-sensing ion channel 1a in cortical lesions of
      patients with focal cortical dysplasia.
AB  - Focal cortical dysplasia (FCD) represents a well-recognized cause of medically
      intractable epilepsy. Previous studies have indicated that seizures can reduce
      brain pH and then eliminate seizure discharges. Acid-sensing ion channels (ASICs)
      are H(+)-gated cation channels that are widely expressed in the central and
      peripheral nervous systems. To understand the potential roles of ASIC1a in the
      epileptogenesis of FCD, we investigated the expression and distribution patterns
      of ASIC1a in surgical specimens from patients with FCD and age-matched normal
      cortices (CTX). Decreased ASIC1a messenger RNA (mRNA) and protein expression were
      detected in FCD compared with CTX. Moreover, the expression of ASIC1a was
      significantly lower in FCD type II than FCD type I. Immunohistochemistry results
      indicated that the overall immunoreactivity of the ASIC1a staining was diminished
      in the dysplastic cortices of FCD compared to the CTX samples. In FCD, ASIC1a
      immunoreactivity was mainly observed in reactive astrocytes and a minority of
      malformed cells, including hypertrophic neurons, dysmorphic neurons, and balloon
      cells. Confocal analysis demonstrated that most malformed cells expressing ASIC1a
      were co-labeled with neuronal rather than astrocytic markers, indicating a
      neuronal lineage. In conclusion, the downregulation and altered cellular
      distribution of ASIC1a in FCD suggest that ASIC1a may potentially contribute to
      the epileptogenesis of FCD. 

PMID- 24682894
TI  - Abstracts of the EuroHeartCare 2014, April 4-5, 2014 , Stavanger, Norway.

PMID- 24682893
TI  - Birth defects, causal attributions, and ethnicity in the national birth defects
      prevention study.
AB  - In order to translate research findings into effective prevention strategies, it
      is important to understand people's beliefs about the causes of poor health
      outcomes. However, with the exception of knowledge and beliefs about folic acid
      supplementation, little is known regarding women's causal attributions women
      regarding birth defects. We employed Attribution Theory constructs to analyze
      open-text interview responses from 2,672 control mothers in the National Birth
      Defects Prevention Study who gave birth in 1997-2005. Common themes included use
      of alcohol, tobacco, illicit drugs, and medications during pregnancy. Stress and
      emotional upset were also suggested as possible causes of birth defects. Genetic-
      and heredity-related responses were more likely to be mentioned by Asian/Pacific
      Islander women compared to non-Hispanic Whites. Hispanic women were less likely
      to suggest several specific possible teratogens, such as paint, pesticides, or
      other chemicals, but were more likely to suggest events occurring during
      childbirth. Differences also emerged among ethnic groups for theoretical
      constructs, although most responses were categorized as controllable, changeable
      over time, and with an internal locus of causality. 

PMID- 24682895
TI  - Expression of LATS1 contributes to good prognosis and can negatively regulate YAP
      oncoprotein in non-small-cell lung cancer.
AB  - Large tumor suppressor (LATS) is a Ser/Thr kinase originally isolated from
      Drosophila. Recent studies demonstrate that LATS is an important member of the
      Hippo pathway which can regulate organ size and cell proliferation. However,
      little is known about the expression and clinical significance of LATS in lung
      cancer. In this study, we aimed to assess the clinical significance and
      biological functions of LATS1 in non-small-cell lung cancer (NSCLC). We
      investigated the expression of LATS1 in 136 cases of NSCLC tissue and 30 cases of
      normal lung tissue by immunohistochemical staining. The results confirmed that
      LATS1 expression was higher in normal lung tissues, but significantly lower in
      NSCLC tissues. Moreover, the expression of LATS1 in NSCLC was significantly
      correlated with p-TNM stage (p = 0.038) and lymph node metastasis (p = 0.014).
      Importantly, the loss of LATS1 expression was associated with short overall
      survival. Further study in NSCLC cell lines in which LATS1 was either
      overexpressed or depleted confirmed that LATS1 markedly inhibited cell
      proliferation and invasion and could regulate the nuclear location of yes
      associated protein (YAP). These results indicate that LATS1 may play an important
      role in NSCLC, and may serve as a novel therapeutic target of NSCLC.

PMID- 24682897
TI  - Metallic ion content and damage to the DNA in oral mucosa cells patients treated
      dental implants.
AB  - The aim of this study was to assess the potential genotoxicity of dental
      implants, evaluating biomarkers of DNA damage (micronuclei and/or nuclear buds),
      cytokinetic defects (binucleated cells) and the presence of trace metals in
      gingival cells of patients with implants, comparing these with a control group. A
      total of 60 healthy adults (30 patients with dental implants and 30 control
      patients without) were included in the study. Medical and dental histories were
      made for each including life-style factors. Genotoxicity effects were assessed by
      micronucleus assays in the gingival epithelial cells of each patient; 1,000
      epithelial cells were analyzed, evaluating the frequency of micronucleated cells
      and other nuclear anomalies. The concentration of metals (Al(27), Ag(107), Co
      (59), Cr (52), Cu(63), Fe(56), Sn(118), Mn(55), Mo(92), Ni(60), Pb(208), Ti(47))
      were assayed by means of coupled plasma-mass spectrophotometry (ICP-MS). The
      frequency of micronuclei in the patient group with implants was higher than in
      the control group but without statistically significant differences (P > 0.05).
      Similar results were found for binucleated cells and nuclear buds (P > 0.05). For
      metals assayed by ICP-MS, significant differences were found for Ti(47) (P <=
      0.045). Univariate analysis identified a significant association between the
      presence of micronuclei and age. Dental implants do not induce DNA damage in
      gingival cells, the slight effects observed cannot be indicated as biologically
      relevant. 

PMID- 24682896
TI  - Antibacterial and bioactive calcium titanate layers formed on Ti metal and its
      alloys.
AB  - An antibacterial and bioactive titanium (Ti)-based material was developed for use
      as a bone substitute under load-bearing conditions. As previously reported, Ti
      metal was successively subjected to NaOH, CaCl2, heat, and water treatments to
      form a calcium-deficient calcium titanate layer on its surface. When placed in a
      simulated body fluid (SBF), this bioactive Ti formed an apatite layer on its
      surface and tightly bonded to bones in the body. To address concerns regarding
      deep infection during orthopedic surgery, Ag(+) ions were incorporated on the
      surface of this bioactive Ti metal to impart antibacterial properties. Ti metal
      was first soaked in a 5 M NaOH solution to form a 1 MUm-thick sodium hydrogen
      titanate layer on the surface and then in a 100 mM CaCl2 solution to form a
      calcium hydrogen titanate layer via replacement of the Na(+) ions with Ca(2+)
      ions. The Ti material was subsequently heated at 600  degrees C for 1 h to
      transform the calcium hydrogen titanate into calcium titanate. This heat-treated
      titanium metal was then soaked in 0.01-10 mM AgNO3 solutions at 80  degrees C for
      24 h. As a result, 0.1-0.82 at.% Ag(+) ions and a small amount of H3O(+) ions
      were incorporated into the surface calcium titanate layers. The resultant
      products formed apatite on their surface in an SBF, released 0.35-3.24 ppm Ag(+)
      ion into the fetal bovine serum within 24 h, and exhibited a strong antibacterial
      effect against Staphylococcus aureus. These results suggest that the present Ti
      metals should exhibit strong antibacterial properties in the living body in
      addition to tightly bonding to the surrounding bone through the apatite layer
      that forms on their surfaces in the body. 

PMID- 24682898
TI  - Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through
      the JAK/STAT pathway in cultured sensory neurons derived from streptozotocin
      induced diabetic rodents.
AB  - Mitochondrial dysfunction occurs in sensory neurons and contributes to diabetic
      neuropathy. Ciliary neurotrophic factor (CNTF) stimulates axon regeneration in
      type 1 diabetic rodents and prevents deficits in axonal caliber, nerve
      conduction, and thermal sensation. We tested the hypothesis that CNTF enhances
      sensory neuron function in diabetes through JAK/STAT (Janus kinase/signal
      transducers and activators of transcription) signaling to normalize impaired
      mitochondrial bioenergetics. The effect of CNTF on gene expression and neurite
      outgrowth of cultured adult dorsal root ganglia (DRG) sensory neurons derived
      from control and streptozotocin (STZ)-induced diabetic rodents was quantified.
      Polarization status and bioenergetics profile of mitochondria from cultured
      sensory neurons were determined. CNTF treatment prevented reduced STAT3
      phosphorylation (Tyr 705) in DRG of STZ-diabetic mice and also enhanced STAT3
      phosphorylation in rat DRG cultures. CNTF normalized polarization status of the
      mitochondrial inner membrane and corrected the aberrant oligomycin-induced
      mitochondrial hyperpolarization in axons of diabetic neurons. The mitochondrial
      bioenergetics profile demonstrated that spare respiratory capacity and
      respiratory control ratio were significantly depressed in sensory neurons
      cultured from STZ-diabetic rats and were corrected by acute CNTF treatment. The
      positive effects of CNTF on neuronal mitochondrial function were significantly
      inhibited by the specific JAK inhibitor, AG490. Neurite outgrowth of sensory
      neurons from age-matched control and STZ-induced diabetic rats was elevated by
      CNTF and blocked by AG490. We propose that CNTF's ability to enhance axon
      regeneration and protect from fiber degeneration in diabetes is associated with
      its targeting of mitochondrial function and improvement of cellular
      bioenergetics, in part, through JAK/STAT signaling. 

PMID- 24682899
TI  - First report of prey capture from human laid snare-traps by wild chimpanzees.
AB  - Chimpanzees regularly hunt for meat in the wild, including both solo and group
      hunting; however, theft of prey from non-chimpanzee hunters, or scavenging of
      carcasses is extremely rare. Here we report the first observations of a novel
      prey capture technique by the chimpanzees in two adjacent communities in the
      Budongo Conservation Field Station, Uganda. In both cases blue duikers were found
      caught in human laid snare traps, and then retrieved by the chimpanzees. In one
      case the duiker was still alive when retrieved and subsequently fully consumed by
      the chimpanzees. In the other, the chimpanzees encountered the duiker while
      alive, but retrieved it soon after its death; here only a small portion was
      consumed. These observations are discussed in comparison to observations of
      chimpanzee hunting, scavenging, and their exploitation of an environment
      increasingly modified by human activity.

PMID- 24682900
TI  - Sleep-wake and melatonin pattern in craniopharyngioma patients.
AB  - OBJECTIVE: To assess the influence of craniopharyngioma or consequent surgery on
      melatonin secretion, and the association with fatigue, sleepiness, sleep pattern
      and sleep quality. DESIGN: Cross-sectional study. METHODS: A total of 15
      craniopharyngioma patients were individually matched to healthy controls. In this
      study, 24-h salivary melatonin and cortisol were measured. Sleep-wake patterns
      were characterised by actigraphy and sleep diaries recorded for 2 weeks.
      Sleepiness, fatigue, sleep quality and general health were assessed by
      Multidimensional Fatigue Inventory, Pittsburgh Sleep Quality Index, Epworth
      Sleepiness Scale and Short-Form 36. RESULTS: Patients had increased mental
      fatigue, daytime dysfunction, sleep latency and lower general health (all,
      P<=0.05), and they tended to have increased daytime sleepiness, general fatigue
      and impaired sleep quality compared with controls. The degree of hypothalamic
      injury was associated with an increased BMI and lower mental health (P=0.01).
      High BMI was associated with increased daytime sleepiness, daytime dysfunction,
      mental fatigue and lower mental health (all, P<=0.01). Low midnight melatonin was
      associated with reduced sleep time and efficiency (P<=0.03) and a tendency for
      increased sleepiness, impaired sleep quality and physical health. Midnight
      melatonin remained independently related to sleep time after adjustment for
      cortisol. Three different patterns of melatonin profiles were observed; normal
      (n=6), absent midnight peak (n=6) and phase-shifted peak (n=2). Only patients
      with absent midnight peak had impaired sleep quality, increased daytime
      sleepiness and general and mental fatigue. CONCLUSION: Craniopharyngioma patients
      present with changes in circadian pattern and daytime symptoms, which may be due
      to the influence of the craniopharyngioma or its treatment on the hypothalamic
      circadian and sleep regulatory nuclei.

PMID- 24682901
TI  - Effect of adenine sulphate interaction on growth and development of shoot
      regeneration and inhibition of shoot tip necrosis under in vitro condition in
      adult Syzygium cumini L.--a multipurpose tree.
AB  - An efficient method for cloning Syzygium cumini (above 40 years old) through
      mature nodal segments has been successfully developed and that could be exploited
      for large-scale production of this valuable multipurpose tree. Nodal segments
      from mature tree were taken as explants and cultured on MS basal medium with
      different cytokinins (BA, Kin, AdS). The application of BA proved to be the best
      responsive cytokinin for the induction of shoot buds and shoots, but the
      proliferated shoots exhibited slower and stunted growth accompanied with
      abscission of leaves and shoot tip necrosis (STN). The problem of leaf abscission
      and STN was considerably reduced by the application of an adjuvant, adenine
      sulphate (AdS) in the optimal medium which led to the production of a maximum of
      14 shoots. Further improvement in shoot bud regeneration and improved growth
      pattern of the regenerating tissue was obtained on the media comprised of MS + BA
      (10 MUM) + GA3 (2.5 MUM). A total number of 15 shoots with mean shoot length of
      5.9 cm was obtained. The healthy elongated shoots were then rooted on MS basal
      augmented with NAA (5 MUM). The plantlets obtained were healthy and were
      successfully acclimatized and transferred under field condition with 70 %
      survival rate. 

PMID- 24682902
TI  - Quercetin and hyperthermia modulate cisplatin-induced DNA damage in tumor and
      normal tissues in vivo.
AB  - Nephrotoxicity, hepatotoxicity, myelosuppression, and genotoxicity are the major
      limitation for the clinical use of cisplatin as an anti-tumoural drug.
      Hyperthermia enhances the clastogenicity of cisplatin. In addition, hyperthermia
      is a promising approach for cancer therapy because it not only kills cancer cells
      directly, but also activates anti-cancer immunity as an indirect effect. The aim
      of this study was to determine whether preventive treatment with quercetin (QU)
      can reduce cisplatin-induced DNA damage in liver, kidney and blood cells and
      whether QU has the potential to serve as a beneficial supplement before cisplatin
      hyperthermal intraperitoneal chemotherapy (HIPEC) in order to gain
      immunomodulatory responses of mice to the tumor. Preventive treatment of mice
      with QU (50 mg kg(-1)) had a protective effect on cisplatin-induced DNA damage in
      normal cells, except kidney cells, in both normothermic and hyperthermic
      conditions without interfering with the antitumor efficacy of the combined
      regimen. Immunostimulation by QU is stressed as an important factor in the tumor
      inhibiting effect of hyperthermia in addition to the well known selective heat
      killing of neoplastic cells. In conclusion, these results suggested that
      preventive treatment with QU could protect the blood, liver and kidney cells of
      mice against HIPEC-induced injury and increase survival of mice by improving the
      antitumor adaptive immunity with hyperthermia.

PMID- 24682904
TI  - Letter regarding Wang et al. entitled "Effects of murine double minute 2
      polymorphisms on the risk and survival of osteosarcoma: a systematic review and
      meta-analysis".

PMID- 24682903
TI  - Extracellular signal-regulated kinase (ERK) expression and activation in mobile
      tongue squamous cell carcinoma: associations with clinicopathological parameters
      and patients survival.
AB  - Extracellular signal-regulated kinase (ERK) has been considered as a critical
      regulator of diverse cellular processes such as proliferation, survival and
      motility, being implicated in the malignant transformation in several tissue
      types. The present study aimed to evaluate the clinical significance of total
      ERK1 (t-ERK1) and phosphorylated ERK1/2 (p-ERK1/2) protein expression in mobile
      tongue squamous cell carcinoma (SCC). t-ERK1 and p-ERK1/2 protein expression in
      tumour cells and infiltrating the tumour microenvironment lymphoid cells was
      assessed immunohistochemically on 47 mobile tongue SCC tissue samples and was
      analyzed in relation with clinicopathological characteristics, overall and
      disease-free patients' survival. Enhanced nuclear t-ERK1 and p-ERK1/2 expression
      in tumour cells was associated with the absence of perineural invasion (p =
      0.043) and shorter overall patients' survival (log-rank test, p = 0.028),
      respectively. Enhanced t-ERK1 expression in infiltrating lymphoid cells was
      significantly associated with female gender, absence of vascular and perineural
      invasion, lymph node metastases and early depth of invasion (p = 0.008, p =
      0.019, p = 0.011, p = 0.036 and p = 0.001, respectively), as well as with longer
      disease-free survival times (log-rank test, p = 0.038). Enhanced p-ERK1/2
      expression in infiltrating lymphoid cells was significantly associated with the
      presence of vascular invasion and lymph node metastases (p = 0.019 and p = 0.004,
      respectively) and shorter overall patients' survival (log-rank test, p = 0.013).
      In multivariate analysis, p-ERK1/2 expression in tumour cells and infiltrating
      lymphoid cells was identified as independent prognostic factors of overall
      survival (Cox regression analysis, p = 0.045 and p = 0.032, respectively). The
      present study supported evidence that ERK signalling pathway may exert a
      potential role in the pathophysiological aspects of the mobile tongue SCC,
      presenting also potential utility as a biomarker for patients' survival and
      reinforcing the development of novel anti-cancer therapies targeting ERK
      signalling cascade in this type of human malignancy.

PMID- 24682905
TI  - Wound healing activity of Origanum vulgare engineered titanium dioxide
      nanoparticles in Wistar Albino rats.
AB  - The titanium dioxide nanoparticles (TiO2.NPs) were synthesized utilizing Origanum
      vulgare under room temperature. The green synthesized TiO2 NPs excitation was
      confirmed using UV-Vis spectrophotometer at 320 nm. Scanning electron microscopy
      analysis showed TiO2.NPs are spherical in shape and connected with one another.
      Dynamic light scattering analysis results specified high stability in
      nanoparticles, with an average particle size of 341 nm. Fourier transform
      infrared spectroscopy peaks revealed the presence of bioactive functional groups
      in Origanum vulgare aqueous leaf extract much needed for the TiO2.NPs formation.
      X-ray diffraction spectra showed the TiO2.NPs are amorphous in nature.
      Furthermore, the green synthesized TiO2.NPs wound healing activity was examined
      in the excision wound model by measuring wound closure, histopathology and
      protein profiling, revealed significant wound healing activity in Albino rats. In
      conclusion, our results bared TiO2.NPs have delivered a novel therapeutic route
      for wound treatment in clinical practice. 

PMID- 24682906
TI  - GABA and 5-HT chitosan nanoparticles decrease striatal neuronal degeneration and
      motor deficits during liver injury.
AB  - The metabolic alterations resulted from hepatic injury and cell loss lead to
      synaptic defects and neurodegeneration that undoubtedly contribute motor
      deficits. In the present study, GABA and 5-HT chitosan nanoparticles mediated
      liver cell proliferation influenced by growth factor and cytokines and neuronal
      survival in corpus striatum of partially hepatectomised rats was evaluated. Liver
      cell proliferation was initiated and progressed by the combined effect of
      increased expression of growth factor, insulin like growth factor-1 and decreased
      expressions of cytokines, tumor necrosis factor-alpha and Akt-1. This was
      confirmed by the extent of incorporation of thymidine analogue, BrdU, in the DNA
      of rapidly dividing cells. Inappropriate influx of compounds to corpus striatum
      resulting from incomplete metabolism elevated GABAB and 5-HT2A neurotransmissions
      compared to those treated with nanoparticles. This directly influenced cyclic AMP
      response element binding protein, glial cell derived neurotrophic factor and
      brain derived neurotrophic factor in the corpus striatum that facilitate
      neurogenesis, neuronal survival, development, differentiation and
      neuroprotection. Motor deficits due to liver injury followed striatal neuronal
      damage were scored by grid walk and rotarod studies, which confirmed the regain
      of motor activity by GABA and 5-HT chitosan nanoparticle treatment. The present
      study revealed the therapeutic significance of GABA and 5-HT chitosan
      nanoparticles in liver based diseases and related striatal neuronal damage that
      influenced by GABA and 5-HT. 

PMID- 24682907
TI  - Preparation and optimization of calcium fluoride particles for dental
      applications.
AB  - Fluorides are used in dental care due to their beneficial effect in tooth enamel
      de-/remineralization cycles. To achieve a desired constant supply of soluble
      fluorides in the oral cavity, different approaches have been followed. Here we
      present results on the preparation of CaF2 particles and their characterization
      with respect to a potential application as enamel associated fluoride releasing
      reservoirs. CaF2 particles were synthesized by precipitation from soluble NaF and
      CaCl2 salt solutions of defined concentrations and their morphology analyzed by
      scanning electron microscopy. CaF2 particles with defined sizes and shapes could
      be synthesized by adjusting the concentrations of the precursor salt solutions.
      Such particles interacted with enamel surfaces when applied at fluoride
      concentrations correlating to typical dental care products. Fluoride release from
      the synthesized CaF2 particles was observed to be largely influenced by the
      concentration of phosphate in the solution. Physiological solutions with
      phosphate concentration similar to saliva (3.5 mM) reduced the fluoride release
      from pure CaF2 particles by a factor of 10-20 * as compared to phosphate free
      buffer solutions. Fluoride release was even lower in human saliva. The fluoride
      release could be increased by the addition of phosphate in substoichiometric
      amounts during CaF2 particle synthesis. The presented results demonstrate that
      the morphology and fluoride release characteristics of CaF2 particles can be
      tuned and provide evidence of the suitability of synthetic CaF2 particles as
      enamel associated fluoride reservoirs. 

PMID- 24682908
TI  - Resistance to acetylsalicylic acid in patients with type 2 diabetes mellitus is
      associated with lipid disorders and history of current smoking.
AB  - BACKGROUND: Diabetes mellitus (DM) is an important risk factor for stroke.
      Acetylsalicylic acid (ASA) is the most frequently used medication for prevention
      of cardio-cerebral vascular diseases. However, some patients experience ischaemic
      vascular events despite the use of ASA. This phenomenon is known as "aspirin
      resistance" (AR). The aim of this study was to assess the prevalence of AR in
      diabetic patients and search for factors associated with it. MATERIALS AND
      METHODS: The examined group consisted of 96 subjects with diagnosed type 2 DM.
      Platelet function test was performed by the method of whole blood impedance
      aggregometry. RESULTS: Among examined subjects, 51 patients (53.1 %) were
      sensitive to ASA action (ASA responders) and 45 patients (46.9 %) were resistant
      to ASA action (ASA non-responders). No association was found between platelet
      aggregation and gender, age, dose of ASA, known duration of diabetes, BMI, heart
      rate, mean systolic and diastolic blood pressure, and risk factors except for
      current smoking (p = 0.030). ASA non-responders were treated shorter with ASA
      than ASA responders (p = 0.010). The mean total cholesterol (p = 0.020), LDL
      concentration (p = 0.005), HCT (p = 0.010), WBC (p = 0.030), and PLT (p = 0.050)
      were significantly higher in ASA non-responders. No association was found between
      AR and results of other laboratory tests and medications. Multiple logistic
      regression analysis revealed factors associated with AR: current smoking and LDL
      concentration higher than 3.5 mmol/l. CONCLUSIONS: Results of our study did not
      confirm the association between poor glycaemic control in the diabetic patients
      and AR. Resistance to ASA in diabetic patients is associated with lipid disorders
      and history of current smoking.

PMID- 24682909
TI  - Relationship between lower urinary tract symptoms and metabolic syndrome in a
      Chinese male population.
AB  - OBJECTIVES: To investigate whether the metabolic syndrome (MetS) is a risk factor
      for lower urinary tract symptoms (LUTS), as defined by the International Prostate
      Symptom Score in a Chinese male population with benign prostate hyperplasia
      (BPH). METHODS: We retrospectively analyzed the clinical data obtained from 1,052
      Chinese men with BPH. Serum levels of prostate specific antigen, fasting blood
      glucose (FBG), high-density lipoprotein cholesterol, total cholesterol and
      triglyceride were determined and recorded. Multiple logistic regression
      statistical analysis was used to investigate the degree of the association
      between LUTS and MetS. RESULTS: Of the 1,052 enrolled patients, 648 (61.60 %) had
      moderate LUTS and 404 (38.40 %) had severe LUTS. A multiple logistic regression
      analysis showed that age (OR 2.02, 95 % CI 1.04-4.63), FBG (OR 3.65, 95 % CI 1.68
      7.98) and presence of MetS (OR 3.64, 95 % CI 1.24-6.14) were significant
      predictors of severe LUTS. CONCLUSIONS: The results of our study suggest that
      MetS is associated with an increase risk of total volume and annual growth rate
      of prostate.

PMID- 24682910
TI  - The effect of steroid pulse therapy on carbohydrate metabolism in multiple
      myeloma patients: a randomized crossover observational clinical study.
AB  - BACKGROUND: Hyperglycemia is a common, but not well-characterized side effect of
      glucocorticoid treatment. AIM: To study the effect of pulse dexamethasone
      treatment on carbohydrate metabolism among multiple myeloma patients.
      MATERIAL/SUBJECTS AND METHODS: A randomized crossover observational study in a
      teaching hospital with nine myeloma patients (one male, two with known type 2
      diabetes (KDM), mean age 69.0 +/- 6.7 years) were investigated using a standard
      75 g Oral Glucose Tolerance Test (patients without KDM) and a 3-day continuous
      glucose monitoring (CGM--all patients) during and between dexamethasone cycles.
      RESULTS: During dexamethasone treatment patients had elevated 2-h postload
      glucose (12.8 +/- 4.7 vs. 8.7 +/- 3.2 mmol/L, P = 0.024) but similar fasting
      glucose (6.3 +/- 1.4 vs. 5.1 +/- 0.5 mmol/L, P = 0.112). Estimated hourly mean
      interstitial glucose values based on linear mixed models showed an increase of
      0.03 [SE 0.01] mmol/L per hour from 5.0 [0.4] in patients without KDM and
      followed a quadratic curve from 5.0 [0.4] mmol/L at midnight to 7.5 [0.5] mmol/L
      at 12:00 h in patients with KDM during control periods. During dexamethasone
      treatment glucose was similar to control periods between 02:00 and 12:00 h in the
      non-KDM group, where they followed a cubic trajectory from 5.3 [0.4] mmol/L at
      04:00 h to 7.3 [0.4] mmol/L at 18:00 h. In contrast, interstitial glucose was
      increased by at least 7.9 [0.3] mmol/L throughout the day in KDM patients during
      dexamethasone treatment and increased from 13.6 [0.5] mmol/L at midnight to 17.5
      [0.5] mmol/L at 17:00 h. CONCLUSIONS: During pulse steroid therapy of myeloma
      patients without KDM afternoon and evening glucose measurements may be the
      optimal tools to characterize glucose metabolism.

PMID- 24682911
TI  - Clinical study of exercise on improvement of beta-cell function and insulin
      resistance in non-diabetic young offsprings of diabetic patients.
AB  - BACKGROUND: Previous studies have shown that exercise could improve beta-cell
      function in humans or animal models of type 2 diabetes. However, whether it can
      prevent the progression of pre-diabetes to diabetes remains unclear. AIM: To
      study the effects of exercise on glycolipid metabolism, beta-cell function, and
      insulin resistance in the non-diabetic young offsprings of diabetic patients.
      METHODS: One hundred and eighty-two normal glucose tolerance young offsprings of
      type 2 diabetic parents were enrolled. Individuals with fasting insulin >= 12.0
      mU/L were assigned to hyperinsulinemia group (n = 72) and those with fasting
      insulin <12.0 mU/L were assigned to normal group (n = 110). The subjects in
      hyperinsulinemia group received 12-week exercise intervention. A 75-g oral
      glucose tolerance test and insulin release test were conducted before and after
      intervention. The area under curve of glucose (AUCglu), area under curve of
      insulin (AUCINS), HOMA insulin resistance index (HOMA-IR), HOMA beta-cell
      function (HOMA-beta), and early insulin secretion index (DeltaI 30/DeltaG 30)
      were calculated. Body composition was measured by dual energy X-ray
      absorptiometry. RESULTS: At baseline, AUCINS and HOMA-beta in hyperinsulinemia
      group were significantly higher compared with the normal group (P < 0.05). After
      the 12-week exercise intervention, no significant changes in blood pressure, body
      mass index, blood glucose, serum lipids, and percentage of body fat were found in
      hyperinsulinemia group; however, AUCINS, HOMA-beta, HOMA-IR (P < 0.05) and DeltaI
      30/DeltaG 30 (P < 0.01) were significantly decreased. CONCLUSIONS: Exercise is
      effective for preventing pre-diabetic insulin resistance and beta-cell
      dysfunction in non-diabetic young offsprings of diabetic patients.

PMID- 24682912
TI  - Serum uric acid is associated with arterial stiffness in men with newly diagnosed
      type 2 diabetes mellitus.
AB  - BACKGROUND: Increased serum uric acid levels and vascular atherosclerosis are
      very common in diabetes. However, few studies focused on the relationship between
      serum uric acid and aortic or peripheral arterial stiffness in newly diagnosed
      diabetic patients. This study investigated the association between serum uric
      acid levels and carotid-femoral pulse wave velocity (cfPWV) or carotid-radial
      (cr) PWV in male patients with newly diagnosed type 2 diabetes mellitus (T2DM).
      METHODS: 106 male patients with newly diagnosed T2DM were recruited. cfPWV and
      crPWV as well as anthropometric parameters, blood pressure, serum uric acid,
      blood glucose, fasting insulin, C-reactive protein and blood lipids were
      measured. RESULTS: The subjects were divided into low uric acid (UA) subgroup and
      high UA subgroup according to uric acid median. cfPWV and crPWV were
      significantly higher in high UA subgroup. Serum uric acid significantly
      correlated with cfPWV (r = 0.533, P < 0.001), crPWV (r = 0.334, P = 0.001), waist
      circumference (r = 0.350, P < 0.001), waist-to-hip ratio (r = 0.254, P = 0.009),
      fasting insulin (r = 0.432, P < 0.001), HOMA-IR (r = 0.173, P = 0.042), fasting
      blood glucose (r = -0.271, P = 0.005), haemoglobin A1c (r = -0.202, P = 0.038),
      and HDL-cholesterol (r = -0.267, P = 0.006) after correction for age. Stepwise
      multiple regressions showed that the independent determinants of cfPWV were serum
      uric acid, age, C-reactive protein, HDL-cholesterol, and smoking status. And the
      independent determinants of crPWV were serum uric acid, age, diastolic blood
      pressure, and HDL-cholesterol. CONCLUSIONS: Serum uric acid is significantly
      associated with increased aortic and peripheral arterial stiffness in men with
      T2DM at the early stage.

PMID- 24682913
TI  - Pantoprazole may improve beta cell function and diabetes mellitus.
AB  - BACKGROUND: Proton pump inhibitors induce hypergastrinemia by suppressing gastric
      acidity. Gastrin has incretin-like stimulating actions on beta cells. Proton pump
      inhibitors have been shown to decrease glycosylated hemoglobin. AIM: We aimed to
      observe changes in beta cell function in diabetic and non-diabetic subjects given
      pantoprazole for an acid-related ailment. METHODS: Seventy-nine male patients (38
      non-diabetic and 41 type-2 diabetic receiving only metformin therapy) were
      followed for 12 weeks after pantoprazole 40 mg/day was given. Fasting plasma
      glucose, HbA1c, fasting insulin, Pancreatic B cell function (HOMA-B), proinsulin
      and c-peptide levels were measured before and after the treatment. RESULTS: In
      non-diabetic patients (n = 38), FPG decreased, whereas c-peptide, log-HOMA-B,
      increased significantly (p = 0.002, p = 0.03, p = 0.042, respectively) after 12
      weeks of pantoprazole administration. In type 2 diabetic patients, FPG, HbA1c and
      weight decreased, whereas log-HOMA-B, c-peptide and log-proinsulin levels
      increased significantly after pantoprazole treatment (p = 0.003, p = 0.007, p <
      0.001; p < 0.001; p = 0.017, p = 0.05, respectively). After pantoprazole
      treatment, pancreatic B-cell function was correlated with c-peptide and insulin
      and inversely with FBG and HbA1c levels in the whole group (r = 0.37, p = 0.001;
      r = 0.60, p < 0.001, r = -0.29, p = 0.011 and r = -0.28, p = 0.013,
      respectively). After pantoprazole treatment, HbA1c was correlated with FBG (r =
      0.75, p < 0.001) and inversely with only log-HOMA-B level (r = -0.28, p = 0.013).
      CONCLUSIONS: Pantoprazole administration seems to correlate with increased beta
      cell function. Pantoprazole administration improves HbA1c, HOMA-B, c-peptide and
      proinsulin levels. Since beta cell loss plays a significant role in the
      pathogenesis of type 2 diabetes, PPI-based therapies may be useful in the
      treatment of diabetes.

PMID- 24682915
TI  - Protective effects of pioglitazone against immunoglobulin deposition on heart of
      streptozotocin-induced diabetic rats.
AB  - AIM: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have
      immunomodulatory and anti-inflammatory effects. The study investigated the
      autoimmune injuries of diabetic cardiomyopathy (DCM) and tested the hypothesis
      that PPAR-gamma agonists suppress disordered immune responses in diabetic heart,
      thereby preventing evolution of DCM. METHODS: STZ-induced diabetic rats were
      assigned to five groups: DM group, given no treatment; INS group, given insulin
      (4 U kg(-1) d(-1)); PIL group, given low dose pioglitazone (4 mg kg(-1) d(-1));
      PIL/INS group, given both low dose pioglitazone and insulin; PIH group, given
      high dose pioglitazone (20 mg kg(-1) d(-1)). Normal rats (CON group) were also
      monitored as control. The pathologic abnormalities of hearts were observed. The
      immunoglobulin deposition was examined by immunohistochemistry and
      immunofluorescence. RESULTS: At 16 weeks, interstitial fibrosis was shown in
      diabetic heart which was accompanied by plenty of inflammatory cells infiltrated.
      Pioglitazone therapy could ameliorate the cardiac injuries. Shown by
      immunohistochemistry, the difference of integrated optical density (IOD) of
      immunoglobulin deposition among each group had statistic significance. No obvious
      immunoglobulins were deposited in the intercellular substance of heart in CON
      group (IgA 290.8 +/- 88.1, IgG 960.4 +/- 316.0 and IgM 341.3 +/- 67.9). But the
      deposition of immunoglobulins increased significantly in DM group (IgA 7,047.5 +/
      1,328.3, P < 0.05; IgG 28,945.9 +/- 5,160.7, P < 0.05 and IgM 8,580.8 +/-
      1,336.8, P < 0.05). Administration of pioglitazone greatly reduced the increased
      deposition in a dose-dependent fashion. Moreover, the statistical significance
      was the same with immunofluorescence analysis as with immunohistochemical
      examination. CONCLUSIONS: The data suggest that disordered immune responses play
      an important role in the pathogenesis of DCM. Pioglitazone showed protective
      effects by inhibiting the immunoglobulin deposition on diabetic myocardium.

PMID- 24682916
TI  - Do the Medicaid and Medicare programs compete for access to health care services?
      A longitudinal analysis of physician fees, 1998-2004.
AB  - As the demand for publicly funded health care continues to rise in the U.S.,
      there is increasing pressure on state governments to ensure patient access
      through adjustments in provider compensation policies. This paper longitudinally
      examines the fees that states paid physicians for services covered by the
      Medicaid program over the period 1998-2004. Controlling for an extensive set of
      economic and health care industry characteristics, the elasticity of states'
      Medicaid fees, with respect to Medicare fees, is estimated to be in the range of
      0.2-0.7 depending on the type of physician service examined. The findings
      indicate a significant degree of price competition between the Medicaid and
      Medicare programs for physician services that is more pronounced for cardiology
      and critical care, but not hospital care. The results also suggest several policy
      levers that work to either increase patient access or reduce total program costs
      through changes in fees. 

PMID- 24682914
TI  - Increased amino acids levels and the risk of developing of hypertriglyceridemia
      in a 7-year follow-up.
AB  - BACKGROUND: Recently, five branched-chain and aromatic amino acids were shown to
      be associated with the risk of developing type 2 diabetes (T2D). AIM: We set out
      to examine whether amino acids are also associated with the development of
      hypertriglyceridemia. MATERIALS AND METHODS: We determined the serum amino acids
      concentrations of 1,125 individuals of the KORA S4 baseline study, for which
      follow-up data were available also at the KORA F4 7 years later. After exclusion
      for hypertriglyceridemia (defined as having a fasting triglyceride level above
      1.70 mmol/L) and diabetes at baseline, 755 subjects remained for analyses.
      RESULTS: Increased levels of leucine, arginine, valine, proline, phenylalanine,
      isoleucine and lysine were significantly associated with an increased risk of
      hypertriglyceridemia. These associations remained significant when restricting to
      those individuals who did not develop T2D in the 7-year follow-up. The increase
      per standard deviation of amino acid level was between 26 and 40 %. CONCLUSIONS:
      Seven amino acids were associated with an increased risk of developing
      hypertriglyceridemia after 7 years. Further studies are necessary to elucidate
      the complex role of these amino acids in the pathogenesis of metabolic disorders.

PMID- 24682917
TI  - Epidemiological implications of HIV-hepatitis C co-infection in South and
      Southeast Asia.
AB  - We sought to profile the epidemiological implication of human immunodeficiency
      virus (HIV) and hepatitis C virus (HCV) co-infection from South and Southeast
      Asia by reviewing original studies reporting prevalence of HIV-HCV co-infection
      and their risk factors. Thirteen papers cited in the PubMed database and
      published in 2012 and 2013 were reviewed. The overall HCV co-infection prevalence
      ranged broadly from 1.2 % to 98.5 % among HIV-positive people in South and
      Southeast Asia. Among HCV seropositive blood donors in Nepal, 5.75 % had HIV co
      infection. Injecting drug use (IDU) was one of the key risk factors of co
      infection, with HCV infection reaching 89.8 % and 98.5 % among HIV-positive
      injecting drug users in Vietnam. The most recent data from South and Southeast
      Asia suggest the urgency of implementation of comprehensive prevention and
      control strategies of HIV-HCV co-infection.

PMID- 24682919
TI  - Evaluation of selenium, redox status and their association with plasma
      amyloid/tau in Alzheimer's disease.
AB  - The aim of the study was to evaluate blood selenium and antioxidants as possible
      oxidative stress markers in Alzheimer's disease (AD) along with amyloid beta42
      (Abeta42) and tau by comparing them with vascular dementia (VD) and age-matched
      healthy controls. Selenium, total tau, Abeta42, glutathione (GSH) and
      malondialdehyde (MDA) levels and the activities of antioxidant enzymes were
      analysed in the blood of AD patients (n = 30), VD patients (n = 35) and controls
      (n = 40) from South India. Plasma Abeta42 level was significantly higher (P <
      0.001) in both AD and VD compared to controls. Total tau and tau-to-amyloid ratio
      were significantly lower in both AD and VD (P < 0.001), compared to controls, and
      a significant difference (P < 0.01 and P < 0.05, respectively) was also observed
      between AD and VD. The receiver operating characteristic (ROC) curve-derived
      cutoff values of <3.5 for tau-to-Abeta42 ratio and <520 pg/ml for total tau
      showed sensitivity and specificity of around 67-72 % for differentiating AD from
      VD and around 90 % for AD from controls, indicating that they could serve as
      reliable AD-specific markers. The MDA levels were significantly higher (P <
      0.001) in both dementia groups along with a significant decrease (P < 0.001) in
      reduced GSH levels, indicating elevated oxidative stress and altered redox status
      in both forms of dementia. Selenium levels did not vary significantly between the
      three groups. The activity of glutathione peroxidase increased in both AD and VD
      compared to controls, with a concomitant decrease in glutathione reductase and
      glucose-6-phospate dehydrogenase (P < 0.001) activity. The activity of
      thioredoxin reductase was significantly lower in both patient groups (P < 0.001)
      compared to healthy controls. No correlation was observed between selenium and
      activities of selenoenzymes, tau, Abeta42 or tau-to-Abeta42 ratio, when analysing
      independently, indicating that blood selenium may not be directly involved in
      Abeta production and in regulating tau/Abeta42-mediated mechanism in AD. The
      present study emphasizes the enhanced oxidative stress in AD pathology and plasma
      tau and tau-to-amyloid ratio as possible markers to differentiate AD from VD. The
      study also points that blood selenium may not be involved in regulating oxidative
      stress in AD, and a longitudinal study correlating plasma and cerebrospinal fluid
      (CSF) selenium and selenoprotein levels is warranted.

PMID- 24682918
TI  - The influence of ethnicity and gender on navigating an acute coronary syndrome
      event.
AB  - BACKGROUND: Ethnicity and gender may influence acute coronary syndrome patients
      recognizing symptoms and making the decision to seek care. OBJECTIVE: To examine
      these potential differences in European (Caucasian), Chinese and South Asian
      acute coronary syndrome patients. METHODS: In-depth interviews were conducted
      with 20 European (Caucasian: 10 men/10 women), 18 Chinese (10 men/eight women)
      and 19 South Asian (10 men/nine women) participants who were purposively sampled
      from those participating in a large cohort study focused on acute coronary
      syndrome. Analysis of transcribed interviews was undertaken using constant
      comparative methods. RESULTS: Participants followed the process of: having
      symptoms; waiting/denying; justifying; disclosing/ discovering; acquiescing;
      taking action. The core category was 'navigating the experience'. Certain
      elements of this process were in the forefront, depending on participants'
      ethnicity and/or gender. For example, concerns regarding language barriers and
      being a burden to others varied by ethnicity. Women's tendency to feel
      responsibility to their home and family negatively impacted the timeliness in
      their decisions to seek care. Men tended to disclose their symptoms to receive
      help, whereas women often waited for their symptoms to be discovered by others.
      Finally, the thinking that symptoms were 'not-urgent' or something over which
      they had no control and concern regarding potential costs to others were more
      prominent for Chinese and South Asian participants. CONCLUSION: Ethnic- and
      gender-based differences suggest that education and support, regarding navigation
      of acute coronary syndrome and access to care, be specifically targeted to ethnic
      communities.

PMID- 24682920
TI  - The effect of a moderate zinc deficiency and dietary fat source on the activity
      and expression of the Delta(3)Delta (2)-enoyl-CoA isomerase in the liver of
      growing rats.
AB  - Auxiliary enzymes participate in beta-oxidation of unsaturated fatty acids. The
      objective of the study was to investigate the impact of a moderate zinc
      deficiency and a high intake of polyunsaturated fat on Delta(3)Delta(2)-enoyl-CoA
      isomerase (ECI) in the liver and other tissues. Five groups of eight weanling
      rats each were fed moderately zinc-deficient (ZD) or zinc-adequate (ZA)
      semisynthetic diets (7 or 50 mg Zn/kg) enriched with 22 % cocoa butter (CB) or 22
      % safflower oil (SO) for 4 weeks: (1) ZD-CB, fed free choice; (2) ZA-CBR, ZA-CB
      diet fed in equivalent amounts consumed by the ZD-CB group; (3) ZD-SO, fed free
      choice; (4) ZA-SOR, ZA-SO diet fed in equivalent amounts consumed by the ZD-SO
      group; and (5) ZA-SO, fed free choice. Growth and Zn status markers were markedly
      reduced in the ZD groups. ECI activity in the liver of the animals fed the ZD-
      and ZA-SO diets were significantly higher (approximately 2- and 3-fold,
      respectively) as compared with the CB-fed animals, whereas activities in
      extrahepatic tissues (kidneys, heart, skeletal muscle, testes, adipose tissue)
      were not altered by dietary treatments. Transcript levels of the mitochondrial
      Eci gene in the liver did not significantly differ between ZD and ZA rats, but
      were 1.6-fold higher in the ZA-SO- than in the ZD-CB-fed animals (P < 0.05). It
      is concluded that diets enriched with safflower oil as a source high in linoleic
      acid induce markedly increased hepatic ECI activities and that a moderate Zn
      deficiency does not affect transcription of the mitochondrial Eci gene in the
      liver. 

PMID- 24682923
TI  - In memoriam: Yoshihiro Hayata (1924-2012).

PMID- 24682921
TI  - Skewed sex ratios and criminal victimization in India.
AB  - Although substantial research has explored the causes of India's excessively
      masculine population sex ratio, few studies have examined the consequences of
      this surplus of males. We merge individual-level data from the 2004-2005 India
      Human Development Survey with data from the 2001 India population census to
      examine the association between the district-level male-to-female sex ratio at
      ages 15 to 39 and self-reports of victimization by theft, breaking and entering,
      and assault. Multilevel logistic regression analyses reveal positive and
      statistically significant albeit substantively modest effects of the district
      level sex ratio on all three victimization risks. We also find that higher male
      to-female sex ratios are associated with the perception that young unmarried
      women in the local community are frequently harassed. Household-level indicators
      of family structure, socioeconomic status, and caste, as well as areal indicators
      of women's empowerment and collective efficacy, also emerge as significant
      predictors of self-reported criminal victimization and the perceived harassment
      of young women. The implications of these findings for India's growing sex ratio
      imbalance are discussed. 

PMID- 24682922
TI  - Differential regulation of microRNAs in response to osmotic, salt and cold
      stresses in wheat.
AB  - MicroRNAs (miRNAs) are tiny non-coding regulatory molecules that modulate plant's
      gene expression either by cleaving or repressing their mRNA targets. To unravel
      the plant actions in response to various environmental factors, identification of
      stress related miRNAs is essential. For understanding the regulatory behaviour of
      various abiotic stresses and miRNAs in wheat genotype C-306, we examined
      expression profile of selected conserved miRNAs viz. miR159, miR164, miR168,
      miR172, miR393, miR397, miR529 and miR1029 tangled in adapting osmotic, salt and
      cold stresses. The investigation revealed that two miRNAs (miR168, miR397) were
      down-regulated and miR172 was up-regulated under all the stress conditions.
      However, miR164 and miR1029 were up-regulated under cold and osmotic stresses in
      contrast to salt stress. miR529 responded to cold alone and does not change under
      osmotic and salt stress. miR393 showed up-regulation under osmotic and salt, and
      down-regulation under cold stress indicating auxin based differential cold
      response. Variation in expression level of studied miRNAs in presence of target
      genes delivers a likely elucidation of miRNAs based abiotic stress regulation. In
      addition, we reported new stress induced miRNAs Ta-miR855 using computational
      approach. Results revealed first documentation that miR855 is regulated by
      salinity stress in wheat. These findings indicate that diverse miRNAs were
      responsive to osmotic, salt and cold stress and could function in wheat response
      to abiotic stresses. 

PMID- 24682924
TI  - Induction of matrix metalloproteinase-3 (MMP-3) expression in the microglia by
      lipopolysaccharide (LPS) via upregulation of glycoprotein nonmetastatic melanoma
      B (GPNMB) expression.
AB  - Substantial evidence suggests that inflammation is an important contributor to
      many neurodegenerative disorders. Activated microglial cells play an important
      role in releasing pro-inflammatory factors, including tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-1beta (IL-1beta) for inducing inflammation. Recently,
      some reports have suggested that glycoprotein nonmetastatic melanoma B (GPNMB) is
      highly expressed in microglia after LPS treatment. However, the role of GPNMB in
      activated microglia is not clearly understood. In this study, we used RT-PCR and
      Western blotting to detect GPNMB and matrix metalloproteinase-3 (MMP-3)
      expressions in activated microglia. GPNMB small interfering RNA (siRNA) or MMP-3
      inhibitor was applied on microglial BV2 cells, and ELISA was performed to measure
      the expressions of TNF-alpha and IL-1beta in BV2 cells. Levels of iNOS and NO in
      BV2 cells were also determined. We found that the levels of GPNMB and MMP-3 were
      significantly increased in BV2 cells after LPS treatment. Moreover, we found that
      GPNMB significantly upregulated the expression of MMP-3 in BV2 cells, and high
      expression of MMP-3 was dependent on the level of GPNMB. Inhibition of GPNMB or
      MMP-3 expression by GPNMB siRNA or MMP-3 inhibitor dramatically suppressed the
      expressions of TNF-alpha, IL-1beta, iNOS, and NO in activated microglia. All of
      these results suggest that GPNMB is involved in the inflammatory responses of
      microglia. 

PMID- 24682925
TI  - Effect of surrounding materials on iterative reconstruction-based line-source
      response function, and annihilations outside the source assessed by a small
      animal PET scanner.
AB  - OBJECTIVE: The aims of this study were (1) to evaluate the effect of surrounding
      materials on the iterative reconstruction-based line-source response function (IR
      RF) of (18)F, (11)C, (13)N, and (15)O using a preclinical PET system, and (2) to
      determine whether and how annihilation outside the source can be visualized
      experimentally. METHODS: We performed all the measurements using the LabPET-8
      PET/CT subsystem built-in the Triumph II platform (TriFoil Imaging, Inc.,
      Northridge, CA, USA). IR-RF was measured for (18)F, (11)C, (13)N, and (15)O, and
      was expressed as full-width at half-maximum (FWHM) and full-width at tenth
      maximum (FWTM) using a glass capillary phantom mounted in materials of various
      densities, which were chosen to cover the wide range of real tissues. To
      determine whether and how annihilation outside the source can be visualized, we
      designed a concentric ring paper phantom, which consisted of a source at the
      center with 4 ring-like paper layers. RESULTS: When the radionuclides were placed
      in air (material density 0 g/cm(3)), IR-RFs were similar among the radionuclides
      tested. As the surrounding material density increased, IR-RFs for higher energy
      emitting radionuclides ((11)C, (13)N, and (15)O) became worse, whereas those of
      (18)F remained relatively constant over the range of surrounding material
      densities (0-2.17 g/cm(3)). Both FWHM and FWTM values were closely correlated
      with mean energy of radionuclides at middle to high material densities (material
      density 0.94-2.17 g/cm(3)). The FWTM/FWHM ratio of high energy-emitting
      radionuclides such as (15)O increased as a function of material density, which
      was followed by subsequent decrease at high material densities (1.2-2.17
      g/cm(3)). Using a concentric ring paper phantom, annihilations outside the source
      were visible and measurable. The innermost layer was visible with all
      radionuclides, whereas the outer layers only with high energy positron emitters.
      CONCLUSIONS: The results indicate that surrounding material affects IR-RF
      particularly for high energy positron emitters. Furthermore, annihilation outside
      the radio-active source can be visualized with some circumstances such as those
      seen with a concentric ring paper phantom.

PMID- 24682927
TI  - The use of a stand-alone interbody fusion cage in subaxial cervical spine trauma:
      a preliminary report.
AB  - BACKGROUND: Anterior spinal surgery has a predominant role in the treatment of
      traumatic lesions of the subaxial cervical spine. Plating is considered
      indispensable to achieve stability but may cause dysphagia, dysphonia, and
      adjacent-level ossification. Zero-P (Synthes GmbH, Oberdorf, Switzerland), an
      anchored interdisc spacer, can be used without an associated plate. The present
      study aimed to test if this new implant would be associated with a low rate of
      dysphagia and other short-term complications compared with the standard for
      anterior spinal fusion surgery and would be able to achieve a solid fusion and
      maintain correct metamere alignment. MATERIAL AND METHODS: This is a preliminary
      presentation of a clinical case series of patients with subaxial cervical
      injuries who underwent anterior interbody fusion. From July 2009 until September
      2011, 12 patients were treated with a Zero-P cage. The data for analysis included
      operating time compared with the standard for spinal fusion surgery with a cage
      plus plate construct, intraoperative blood loss, clinical and radiographic
      results, and complications. RESULTS: In the postoperative period no patient had
      neurologic worsening. One patient experienced transient dysphonia and moderate
      dysphagia. All the patients were followed up for a minimum of 6 months (mean: 13
      months; range: 6-27 months). Stability and fusion were obtained in all patients
      together with correct metamere alignment. CONCLUSION: We presented the
      preliminary results of a clinical case series. Our results support the initiation
      of prospective randomized trials with more patients and longer follow-up.

PMID- 24682926
TI  - Evaluating the possible role of 68Ga-citrate PET/CT in the characterization of
      indeterminate lung lesions.
AB  - We sought to determine whether PET/CT imaging with (68)Ga-citrate could be of
      value in distinguishing benign from malignant lung pathology in a setting with a
      high prevalence of granulomatous diseases. METHODS: Thirty-six consecutive
      patients with indeterminate lung lesions prospectively underwent dual time point
      (60 and 120 min) (68)Ga-citrate PET/CT study prior to lung biopsy. Qualitative
      and semi-quantitative measures of tracer uptake in the lung lesions (SUVmax) were
      compared to the histopathology in order to establish an imaging pattern to
      distinguish benign from malignant lesions. RESULTS: Fourteen patients (38.9 %)
      were diagnosed with a malignant lesion, 12 (33.3 %) with tuberculosis (TB), and
      10 participants (27.8 %) with other benign lung lesions. At 60-min post
      injection, patients who were diagnosed with a malignant lesion (n = 14)
      demonstrated a mean SUVmax of 3.36 +/- 1.14, with a median value of 3.04 (min =
      1.56, max = 4.65).Those with TB (n = 12) demonstrated a SUVmax of 3.99 +/- 2.28,
      and a median value of 3.71 (pct25 = 2.19, pct75 = 4.95). In patients with other
      benign lesions (n = 10), the following values were observed: a SUVmax of 2.70 +/-
      1.31, a median value of 2.50 (pct25 = 1.76, pct75 = 3.59). The mean values of
      these three types of pathology were not statistically significant (p = 0.1919),
      and therefore the SUVmax could not be used to accurately distinguish between
      these lesions using both early and delayed imaging. CONCLUSION: This study, as
      the first (68)Ga-citrate PET/CT in humans for the in vivo imaging of lung
      pathology, demonstrated its potential for the detection of both malignancy and
      TB. However, (68)Ga-citrate seemed incapable of providing a clear distinction
      between malignant and benign lung lesions in a setting with a high prevalence of
      granulomatous diseases such as TB.

PMID- 24682928
TI  - Endonasal endoscopic pituitary adenoma resection: preservation of
      neurohypophyseal function.
AB  - OBJECTIVES: In the past 10 years, endoscopic resection of pituitary adenomas has
      become an alternative to microsurgical resection with the additional advantage of
      increasing the patient's postoperative comfort. This analysis explored whether
      endoscopic resection can reduce the risk of postoperative neurohypophyseal
      dysfunction. DESIGN: We rated and compared the need to administer desmopressin
      during the first four postoperative days and with the need after a follow-up of
      at least 3 months (chronic administration). SETTING: Three groups of patients
      were compared: Patients in group 1 were operated on microscopically. Patients in
      group 2 were operated on endoscopically. Patients in group 3 were operated on
      endoscopically with intraoperative magnetic resonance imaging (iMRI).
      PARTICIPANTS: Group 1 was made up of 50 patients treated in 1999; group 2
      comprised 50 patients operated on from 2006 to 2007; and Group 3 comprised 50
      patients operated on in 2008. MAIN OUTCOME MEASURES: In group 1 the need to use
      desmopressin postoperatively occurred in eight patients; three needed chronic
      treatment. In group 2 the need for postoperative application of desmopressin
      occurred in four patients; none required chronic treatment. In group 3
      desmopressin had to be administered postoperatively in five patients but only
      temporarily. RESULTS AND CONCLUSIONS: Endoscopic surgery is a safe and effective
      method for the resection of pituitary adenomas. The rate of chronic desmopressin
      application was reduced. In conjunction with iMRI and navigation, the endoscopic
      technique allows increased radicality together with fewer adverse effects.

PMID- 24682929
TI  - Tarlov cysts: endoscope-assisted obliteration of the communication with the
      spinal subarachnoid space.
AB  - BACKGROUND AND OBJECTIVE: The physiopathology of Tarlov or perineural cyst (PC)
      symptoms is unknown, but probably its filling and distention with spinal
      cerebrospinal fluid makes them symptomatic. The objective of this study is to
      describe the endoscope-assisted obliteration of the communication between PCs and
      the spinal subarachnoid space (SSS). PATIENTS AND METHODS: From 2007 to 2011,
      four male and two female patients (median age: 45 years) with PCs were treated.
      They complained of lumbar, sciatic, and/or perineal pain. Physical examination
      was normal. The diagnosis was made by magnetic resonance imaging (MRI). All the
      cysts were located in the midline between S1 and S3. An endoscope-assisted
      obliteration between PC and SSS was performed. The outcome was evaluated
      clinically with the Odom scale and radiologically with an MRI. RESULTS: After a
      median follow-up of 25.83 months, the outcome was excellent (four cases), good
      (one case), and poor (one case). There were no complications. The postoperative
      MRI showed size and signal intensity changes in all PCs reflecting their
      exclusion from the SSS. CONCLUSIONS: The endoscope-assisted obliteration of the
      communication between PCs and the SSS is a simple technique that rendered
      excellent to good results in 83% of the cases.

PMID- 24682930
TI  - Imaging findings of primary malignant gastrointestinal stromal tumor of the
      liver.
AB  - A primary gastrointestinal stromal tumor (GIST) arising in the liver is extremely
      rare. In our case of GIST, CT and MRI showed a well-defined, weakly enhancing
      mass with a cystic component in the left lateral segment of the liver that showed
      homogeneous and avid (18)F-fluorodeoxyglucose ((18)F-FDG) accumulation on
      positron emission tomography/computed tomography (PET/CT). We herein present a
      rare case of primary malignant GIST of the liver presenting with peritoneal
      seeding on CT, gadoxetic acid-enhanced MRI and (18)F-FDG PET/CT.

PMID- 24682931
TI  - Cystic intraductal papillary adenocarcinoma of the bile duct of the caudate lobe
      initially manifesting as a simple cyst on CT.
AB  - Cystic-form, intraductal papillary neoplasms of the bile ducts (IPNBs) usually
      manifest as a multilocular cystic mass or unilocular cystic mass with papillary
      mural nodules. To our knowledge, cystic IPNBs forming single, unilocular cystic
      lesions without a visible papillary tumor and mimicking a simple hepatic cyst or
      mucinous cystadenoma have never been reported. Here, we report a case of cystic
      IPNB that initially appeared as a simple cyst and subsequently became a
      unilocular cystic mass with a papillary mural nodule on follow-up CT.

PMID- 24682932
TI  - Rapamycin combined with celecoxib enhanced antitumor effects of mono treatment on
      chronic myelogenous leukemia cells through downregulating mTOR pathway.
AB  - Chronic myelogenous leukemia is a neoplasm of myeloid progenitor cells. We
      recently found that rapamycin could induce G0/G1 phase arrest and apoptosis and
      inhibit proliferation of K562 cells through inhibiting mammalian target of
      rapamycin (mTOR) pathway. However, whether rapamycin has synergistic effects with
      other drugs in chronic myelogenous leukemia (CML) therapies remain unclear.
      Therefore, we examined the effect of rapamycin combined with celecoxib on K562
      cells in vitro. The survival rates showed a significant decrease in rapamycin +
      celecoxib treatment group. The combination treatment also increased the G0/G1
      phase cells as compared to rapamycin or celecoxib treatment alone (P < 0.05),
      accompanied with the decreased population of S phase cells. Meanwhile, the rate
      of apoptosis was 15.87 +/- 2.21 % in rapamycin + celecoxib treatment group,
      significantly higher than that in mono treatment group (P < 0.05). Western blot
      and reverse transcription PCR (RT-PCR) analysis showed that the expressions of
      mTOR, 4E-BP1, and p70S6K were all significantly decreased in K562 cells after
      rapamycin + celecoxib treatment (P < 0.05). In conclusion, rapamycin combined
      with celecoxib could induce cell cycle arrest and apoptosis and decrease the
      expressions of mTOR, 4E-BP1, and p70S6K. It suggested that the combination could
      enhance the antitumor effects of mono treatment on CML cells through
      downregulating mTOR pathway.

PMID- 24682933
TI  - The roles of miR-200c in colon cancer and associated molecular mechanisms.
AB  - The expression of miR-200c has been widely reported to be elevated in tumor
      tissues and sera of patients with colorectal cancer (CRC) and has been found to
      correlate with poor prognosis. However, how miR-200c regulates the apoptosis,
      survival, invasion, metastasis, and tumor growth in colon cancer cells remains to
      be fully elucidated. This study seeks to further investigate the role of miR-200c
      in colon cancer development. The expression of miR-200c in tumor and peritumoral
      tissues of 101 colon cancer patients was measured by real-time PCR. miR-200c
      expression in HCT-116 and HT-29 colon cancer cells was silenced by adenovirus
      carried expression of antisense mRNA against miR-200c. The protein levels of
      PTEN, p53 Ser(15), PP1, and activated caspase-3 in HCT-116 and HT-29 cells were
      measured by Western blot. This study demonstrated that the expression of miR-200c
      was significantly higher in tumor tissues than in peritumoral tissues of colon
      cancer patients. The elevated miR-200c expression significantly correlated with
      the TNM stage, lymph node metastasis, and invasion of colon cancer. Silencing miR
      200c expression significantly induced cell apoptosis, inhibited long-term
      survival, invasion, and metastasis, and delayed xenograft tumor growth.
      Importantly, silencing miR-200c expression sensitized the therapeutic effect of
      Ara-C (Cytarabine). The effects of silencing miR-200c expression were associated
      with upregulation of PTEN protein and p53 Ser(15) phosphorylation levels in HCT
      116 cells and PTEN protein expression in HT-29 cells. In conclusion, miR-200c
      functions as an oncogene in colon cancer cells through regulating tumor cell
      apoptosis, survival, invasion, and metastasis as well as xenograft tumor growth
      through inhibition of PTEN expression and p53 phosphorylation. 

PMID- 24682935
TI  - C-H bond activation during and after the reactions of a metallacyclic amide with
      silanes: formation of a MU-alkylidene hydride complex, its H-D exchange, and beta
      H abstraction by a hydride ligand.
AB  - Metallacyclic complex [(Me2N)3Ta(eta(2)-CH2SiMe2NSiMe3)] (3) undergoes C-H
      activation in its reaction with H3SiPh to afford a Ta/MU-alkylidene/hydride
      complex, [(Me2N)2{(Me3Si)2N}Ta(MU-H)2(MU-C-eta(2)-CHSiMe2NSiMe3)Ta(NMe2)2] (4).
      Deuterium-labeling studies with [D3]SiPh show H-D exchange between the Ta-D-Ta
      unit and all methyl groups in [(Me2N)2{(Me3Si)2N}Ta(MU-D)2(MU-C-eta(2)
      CHSiMe2NSiMe3)Ta(NMe2)2] ([D2]-4) to give the partially deuterated complex [Dn]
      4. In addition, 4 undergoes beta-H abstraction between a hydride and an NMe2
      ligand and forms a new complex [(Me2N){(Me3 Si)2N}Ta(MU-H)(MU-N-eta(2)-C,N
      CH2NMe)(MU-C-eta(2)-C,N-CHSiMe2NSiMe3)Ta(NMe2)2] (5) with a cyclometalated,
      eta(2)-imine ligand. These results indicate that there are two simultaneous
      processes in [Dn]-4:1) H-D exchange through sigma-bond metathesis, and 2) H-D
      elimination through beta-H abstraction (to give [Dn]-5). Both 4 and 5 have been
      characterized by single-crystal X-ray diffraction studies.

PMID- 24682934
TI  - Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer
      cells.
AB  - Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent
      component in hot peppers. The role of capsaicin in carcinogenesis is quite
      controversial. Although some investigators suspect that capsaicin is a
      carcinogen, co-carcinogen, or tumor promoter, others have reported that it has
      chemopreventive and chemotherapeutic effects. The present study aimed to evaluate
      the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5
      flourouracil (5-FU)-treated gastric cancer cells. In this study, the gastric
      cancer cell line HGC-27 was used and capsaicin used as a chemosensitizer and 5
      flourouracil (5-FU) was used as chemotherapeutic. Cytotoxicity and
      chemosensitizing activities were analyzed with MTT assay; supernatant levels of
      LDH and glucose were detected as biochemical markers of cell viability;
      cytochrome c and AIF were evaluated with western blot; and additionally, wound
      healing assays were employed. Results suggested that capsaicin had significant
      anticancer abilities; such capsaicin were capable of causing multifold decreases
      in the half maximal inhibitory concentration IC50 value of 5-FU. The continuing
      controversy surrounding consumption or topical application of capsaicin clearly
      suggests that more well-controlled epidemiologic studies are needed to evaluate
      the safety and efficacy of capsaicin use. In summary, the present study
      demonstrated that capsaicin has the potential to be used for treating gastric
      carcinoma with 5-FU in vitro. 

PMID- 24682937
TI  - Molecular detection of genogroup I and II picobirnaviruses in pigs in China.
AB  - In this study, a total of 187 stool specimens were collected from a pig farm in
      Hunan province of China, from November 2011 to June 2012. 39 (20.9 %) stool
      specimens were positive for picobirnaviruses using reverse transcription
      polymerase chain reaction. Among 39 stool specimens, 84.6 % (33/39) were
      identified to be genogroup I (prototype 1-CHN-97), 38.5 % (15/39) belonged to
      genogroup II (prototype 4-GA-91), and 23.1 % (9/39) of which showed the evidence
      of genogroup I picobirnavirus were also positive for genogroup II
      picobirnaviruses. Picobirnaviruses exist in pigs which were divided into five
      groups according to the age and physiological status. Nineteen representative
      strains of genogroup I picobirnaviruses and eleven strains of genogroup II
      picobirnaviruses detected in this study were selected to analyze their
      phylogenetic relationships with other picobirnaviruses reference strains. The
      phylogenetic tree analysis suggested the prevalence of multiple picobirnaviruses
      in pigs in China.

PMID- 24682938
TI  - Sequence and phylogenetic analysis of surface protein genes of emerging H9N2
      influenza viruses isolated from poultry in two geographical regions of China.
AB  - Subtype H9N2 avian influenza viruses (AIVs) circulating in China have aroused
      increasing concerns for their impact on poultry and risk to public health. The
      present study was an attempt to elucidate the phylogenetic relationship of H9N2
      AIVs in two geographically distinct regions of China where vaccination is
      routinely practiced. A total of 18 emerging H9N2 isolates were identified and
      genetically characterized. Phylogenetic analysis of hemagglutinin (HA) and
      neuraminidase (NA) genes confirmed that the isolates belonged to the Y280
      lineage. Based on the HA genes, the isolates were subdivided into two subgroups.
      The viruses from Zhejiang Province were clustered together in Group I, while the
      isolates from Guangdong Province were clustered together in Group II. Antigenic
      characterization showed that the tested viruses were antigenically different when
      compared to the current used vaccine strain. It was notable that 14 out of total
      18 isolates had an amino acid exchange (Q->L) at position 216 (226 by H3
      Numbering) in the receptor-binding site, which indicated that the virus had
      potential affinity of binding to human like receptor. These results suggest that
      the emerging viruses have potential risk to public health than previously
      thought. Therefore, continuous surveillance studies of H9N2 influenza virus are
      very important to the prognosis and control of future influenza pandemics. 

PMID- 24682939
TI  - Complete genome sequence of a novel infectious bronchitis virus strain
      circulating in China with a distinct S gene.
AB  - An avian infectious bronchitis virus (IBV) was isolated and identified from a
      commercial layer flock vaccinated with live attenuated H120 vaccine in China,
      designed as ck/CH/IBTZ/2012. To determine the origination and evolution of this
      isolated strain, we have carried out a complete genome sequencing of this strain.
      The genome of the ck/CH/IBTZ/2012 strain is 27,691 nucleotides in length and
      includes more than 10 open reading frames. Sequence comparison and phylogenetic
      analysis based on the full-length genomic sequences showed that ck/CH/IBTZ/2012
      is mostly related to the LX4-like strains. However, sequence analysis based on
      the spike protein (S) gene sequences revealed that ck/CH/IBTZ/2012 possesses a
      distinct S gene setting it apart from the Massachusetts-type strains and LX4-type
      strains. The cleavage site within the spike protein (S) of ck/CH/IBTZ/2012 is
      HRRKR, which is different from the majority of the IBVs in China for their
      cleavage sits are HRRRR. Recombination analysis showed that ck/CH/IBTZ/2012 is a
      chimeric virus with a LX4-like backbone except S gene which might be from an
      unknown strain. Based on the data presented in this paper, it can be concluded
      that genetic changes due to adaptive evolution and recombination both contributed
      to the origin of strain ck/CH/IBTZ/2012, which belongs to a new genotype.

PMID- 24682940
TI  - Towards a better quality of life (QoL) for patients with pituitary diseases:
      results from a focus group study exploring QoL.
AB  - PURPOSE: Patients treated for pituitary adenomas generally report a reduced
      quality of life (QoL). At present, the patient's perspective of QoL has not been
      fully addressed and this, and further insight in potential determinants of QoL in
      pituitary diseases is required to design strategies to improve QoL. We aimed to
      define patients' perceived QoL and to identify potential factors they perceive to
      contribute to QoL. METHODS: We conducted four independent focus groups of six
      patients each, per specific pituitary disease (Cushing's disease, Non-functioning
      pituitary macroadenoma, acromegaly, prolactinoma). In two sessions these focus
      groups discussed aspects of QoL. Verbatim transcripts were analyzed using a
      grounded theory approach. RESULTS: The issues raised by the patient groups were
      compatible with statements and items of available QoL questionnaires. In
      addition, other QoL aspects emerged, such as visual limitations (physical
      problems); issues with a desire to have children/family planning, fear of
      collapsing, fear of recurrence, panic, persisting thoughts, problems with an
      altered personality, anger, jealousy, sadness, frustration (psychological
      problems); and difficulties communicating about the disease, lack of sympathy and
      understanding by others, and a reduced social network (social problems). Next,
      this study uncovered factors which might contribute to a decreased QoL (e.g. less
      effective coping strategies, negative illness perceptions, negative beliefs about
      medicines, unmet needs regarding care). CONCLUSIONS: This focus group study
      demonstrated that important disease-specific aspects of QoL are neglected in
      current pituitary disease-specific questionnaires and elucidated potential
      factors that contribute to a decreased QoL. Information provided in this study
      can (and will) be used for developing additional items for disease-specific QoL
      questionnaires and for the development of a self-management intervention aiming
      to improve QoL in patients treated for pituitary diseases.

PMID- 24682941
TI  - Risk factors for hepatitis C infection among Vietnam era veterans versus
      nonveterans: results from the Chronic Hepatitis Cohort Study (CHeCS).
AB  - Research suggests that Vietnam era veterans have a higher prevalence of hepatitis
      C virus (HCV) than other veterans and nonveterans. However, the reasons for this
      are unclear, since this research has been conducted among Department of Veterans
      Affairs (VA) patients and most veterans do not use the VA. The current study
      compares HCV risk factors between the Vietnam era veterans and nonveterans seen
      in 4 large non-VA systems to explain this disparity. A total of 4,636 HCV
      patients completed surveys in 2011-2012. Vietnam era veterans were defined as
      those who served in the military any time between 1964 and 1975. Bivariate tests
      followed by logistic regressions, and multivariable modeling were conducted to
      study risk factors among Vietnam era veterans and nonveterans. Since few veterans
      were female (~2 %), they were excluded. Among male respondents (N = 2,638), 22.5
      % were classified as Vietnam era veterans. Compared to nonveterans, these
      patients were older (p < 0.001), more educated (p < 0.001), less often foreign
      born (p = 0.009), more often married (p < 0.001), less often employed, and less
      likely to have a history of drug abuse treatment (p < 0.001). Comparison of
      specific risk factor differences for HCV infection by veteran status suggested
      that while injection drug use approached statistical significance (nonveterans =
      46.1 % vs. Vietnam era veterans = 41.4 %, p = 0.06), only reported sex with men
      was significant (nonveterans = 2.4 % vs. Vietnam era veterans = 0.6 %, p =
      0.013). In multivariate logistic regression controlling for age, education,
      country of birth, marital status and study site, no HCV risk factor was
      associated with Vietnam era veteran status. However, veterans were more likely to
      report "other" exposures were the source of infection than nonveterans (p <
      0.001). While Vietnam era veterans seen in non-VA facilities do not report a
      higher prevalence of common HCV risk factors, such as injection drug use, they
      are more likely to report "other" exposures, typically associated with military
      service, as the source of HCV infection.

PMID- 24682942
TI  - Protective effects of naringenin on iron-overload-induced cerebral cortex
      neurotoxicity correlated with oxidative stress.
AB  - Iron is a component of several metalloproteins involved in crucial metabolic
      processes such as oxygen sensing and transport, energy metabolism, and DNA
      synthesis. This metal progressively accumulates in the pathogenesis of
      Alzheimer's (AD) and Parkinson's (PD) diseases. Naringenin (NGEN), a natural
      flavonoid compound, has been reported to possess neuroprotective effect against
      PD-related pathology, however, the mechanisms underlying its beneficial effects
      are poorly defined. Thus, the aim of this study is to investigate the potential
      mechanism involved in the cytoprotection of NGEN against iron-induced
      neurotoxicity in the cerebral cortex of Wistar rats. Animals that were given
      repetitive injections of iron dextran for a total of 4 weeks showed a significant
      increase in lipid and protein markers such as thiobarbituric reactive acid
      substances, protein carbonyl product content levels, and DNA apoptosis in the
      cerebral cortex. These changes were accompanied by a decrease of enzymatic
      antioxidants like superoxide dismutase and catalase and in the levels of
      nonenzymatic antioxidants like total thiols and ascorbic acid. The activity of
      glutathione peroxidase remained unchanged in rats. A significant decrease in
      acetylcholinesterase and Na(+)/K(+)-ATPase activities was also shown, with a
      substantial rise in the nitric oxide levels. Coadministration of NGEN to iron
      treated rats significantly improved antioxidant enzyme activities and attenuated
      oxidative damages observed in the cerebral cortex. The potential effect of NGEN
      to prevent iron-induced neurotoxicity was also reflected by the microscopic
      study, indicative of its neuroprotective effects. 

PMID- 24682943
TI  - Nucleolin promotes TGF-beta signaling initiation via TGF-beta receptor I in
      glioblastoma.
AB  - The transforming growth factor beta (TGF-beta) pathway plays a key role in
      oncogenesis of advanced cancers, involving the non-Smad and Smad pathways.
      Meanwhile, nucleolin on the cell surface has been also reported to affect
      activation of signaling pathways. However, the effect of cell surface nucleolin
      on TGF-beta pathway in glioblastoma is not still understood. Here, using
      antibodies of nucleolin and TGF-beta receptor I (TbetaR-I), we observed blocking
      of either nucleolin or TbetaR-I inhibited the phosphorylation of CrkL, Erk1/2,
      and Smad2. Using nucleolin siRNA, nucleolin knockdown was also identified to
      suppress the expression of p-CrkL, p-Erk1/2, and p-Smad2. Furthermore,
      immunoprecipitation revealed the interaction between cell surface nucleolin and
      TbetaR-I on the U87 cell membrane. In addition, U87 cell wound-healing, soft-agar
      and MTT assay also showed si-nucleolin could obviously impair wound closure (p <
      0.001), colony formation (p < 0.001) and cell growth (p < 0.001). In conclusion,
      nucleolin promotes and regulates the TGF-beta pathway by interacting with TbetaR
      I and is required for initiation and activation of TGF-beta signaling. Thus,
      nucleolin could be a key factor in glioblastoma pathogenesis and considered a
      therapeutic target, which may also mediate more signaling pathways.

PMID- 24682945
TI  - [Project to attain the ideal caloric intake level in critical patients within a
      72-hour period].
AB  - BACKGROUND & PROBLEMS: Early enteral nutrition and receiving more than 70% of the
      ideal caloric intake level has been shown to reduce patient infection rates,
      duration of hospital stays, and mortality. Only 40.6% of patients in our surgical
      intensive care unit were achieving the ideal caloric intake level. PURPOSE: This
      project was designed to raise the ratio of those achieving an ideal caloric
      intake level from 40.6% to 70%. RESOLUTIONS: Strategies included: (1) providing
      education related to nutrition, (2) establishing an enteral nutrition flowchart
      and popularizing and carrying out the enteral nutrition flowchart, (3) discussing
      together with doctors and nutritionists about feeding conditions, and (4)
      revising standard procedures for the NG feeding of critical patients. RESULTS:
      Seventy percent of patients in the surgical intensive care unit achieved their
      ideal caloric intake level after implementation of this intervention.
      CONCLUSIONS: This project used interdisciplinary cooperation to improve caloric
      intake among patients in the surgical intensive care unit. The intervention and
      results may be used as a reference by hospitals for improving patient caloric
      intake and hospital quality of care.

PMID- 24682946
TI  - [Improving the accuracy of caregiver-provided in-home total parenteral nutrition
      care].
AB  - BACKGROUND & PROBLEMS: According to current surveys conducted between September
      and December 2011, the accuracy of primary caregiver-administered Home Total
      Parenteral Nutrition Care (HTPNC) was 62.0%. Further, nursing staffs provide
      instruction on HTPNC to only 22.2% of caregivers responsible for administering
      HTPNC. Main related causes were: (1) difficult to comprehend health education
      tools; (2) inconsistent nursing guidelines; (3) a lack of relevant standard
      operating procedures; and (4) poor caregiver adoption of TPN skills. PURPOSE:
      This project was developed to (1) increase the accuracy of primary caregiver
      administered HTPNC to 90% and (2) increase the percentage of nurse-administered
      HTPNC to 90%. RESOLUTIONS: We developed appropriate nursing guidelines, created a
      health education CD-ROM with input from a cross-disciplinary team and total
      parenteral nutrition focus group, designed reusable teaching model aids for
      repetitive practice, and held regular group health education sessions. RESULTS:
      The nursing staff HTPNC instruction rate increased to 100%. Caregiver HTPNC
      implementation accuracy increased to 100% prior to patient discharge.
      CONCLUSIONS: This approach was successful in achieving its stated goals. Further,
      using reusable teaching model aids may reduce caregiver anxiety and increase
      caregiver confidence. The greatest benefit of this project was its extension of
      teaching model aids to relevant units, allowing for routine monitoring by the
      department of nursing quality management.

PMID- 24682948
TI  - On-court demands of elite handball, with special reference to playing positions.
AB  - The aim of this review is to provide the first comprehensive analysis of the
      various technical and physical on-court demands in elite male handball with
      respect to playing positions. While low-intensity activities such as standing
      still and walking represent the greater proportion of playing time (up to ~70 %),
      handball can be considered an intense activity for all players, especially
      because of the large number of repeated high-intensity actions occurring
      throughout the game (e.g., jumps, sprints, changes of direction, duels,
      contacts). Additionally, the substantial number of body contacts likely increases
      neuromuscular load, both during and following games. However, the average running
      pace (53 +/- 7 to 90 +/- 9 m.min(-1)) during handball games tends to be lower
      than in the majority of other team sports, while blood lactate and heart rate
      responses tend to be similar and slightly lower, respectively. Behind these team
      average data, the substantial variations in technical and physiological demands
      between the different positions have been overlooked in the literature. Whether
      physical fatigue actually occurs during games is still unclear since, in the
      majority of studies, games were not examined under actual competitive situations.
      We contend that, in practice, appropriate player rotations may allow players to
      maintain an optimal physical performance level or, at least, limit a possible
      drop in physical/playing efficiency. Future research should essentially focus on
      the technical and physiological responses during games in relation to specific
      collective systems of play and individual playing roles. The occurrence of player
      position-specific fatigue should also be better examined when considering
      individual playing time and rotation strategies. 

PMID- 24682944
TI  - Performance tuning non-uniform sampling for sensitivity enhancement of signal
      limited biological NMR.
AB  - Non-uniform sampling (NUS) has been established as a route to obtaining true
      sensitivity enhancements when recording indirect dimensions of decaying signals
      in the same total experimental time as traditional uniform incrementation of the
      indirect evolution period. Theory and experiments have shown that NUS can yield
      up to two-fold improvements in the intrinsic signal-to-noise ratio (SNR) of each
      dimension, while even conservative protocols can yield 20-40% improvements in the
      intrinsic SNR of NMR data. Applications of biological NMR that can benefit from
      these improvements are emerging, and in this work we develop some practical
      aspects of applying NUS nD-NMR to studies that approach the traditional detection
      limit of nD-NMR spectroscopy. Conditions for obtaining high NUS sensitivity
      enhancements are considered here in the context of enabling (1)H,(15)N-HSQC
      experiments on natural abundance protein samples and (1)H,(13)C-HMBC experiments
      on a challenging natural product. Through systematic studies we arrive at more
      precise guidelines to contrast sensitivity enhancements with reduced line shape
      constraints, and report an alternative sampling density based on a quarter-wave
      sinusoidal distribution that returns the highest fidelity we have seen to date in
      line shapes obtained by maximum entropy processing of non-uniformly sampled data.

PMID- 24682951
TI  - Most hydrogen peroxide-induced histone H2AX phosphorylation is mediated by ATR
      and is not dependent on DNA double-strand breaks.
AB  - The nuclear foci of phosphorylated histone H2AX (gammaH2AX) are frequently used
      as a marker for DNA double-strand breaks (DSBs) following ionizing radiation
      (IR). However, recent studies reported that gammaH2AX foci do not necessarily
      correlate with DSBs under other conditions. We showed that gammaH2AX foci induced
      by oxidative stress in hydrogen peroxide (H2O2)-treated cells displayed several
      different features from those induced by IR. The magnitude of gammaH2AX induction
      was heterogeneous among H2O2-treated cells. Some cells expressed small discrete
      gammaH2AX foci, whereas others expressed a gross gammaH2AX signal that was
      distributed throughout the nucleus. Oxidative stress-induced gammaH2AX was
      eliminated in DSB repair-deficient mutant cells as efficiently as in wild-type
      cells and was not necessarily accompanied by phosphorylated ataxia telangiectasia
      mutated (ATM) or 53BP1 foci. Analyses using specific inhibitors showed that ATM-
      and Rad3-related (ATR), rather than ATM, was the prominent kinase mediating the
      oxidative stress response. These results suggest that a major fraction of
      gammaH2AX induced by oxidative stress is not associated with DSBs. Single
      stranded DNA arisen from stalled replication forks can cause the ATR-mediated
      induction of gammaH2AX. However, oxidative stress appeared to induce gammaH2AX in
      both S- and non-S-phase cells. These results suggest that there may be another
      pathway leading to the ATR-mediated induction of gammaH2AX in non-S-phase cells
      without DSBs. 

PMID- 24682950
TI  - Weight-making strategies in professional jockeys: implications for physical and
      mental health and well-being.
AB  - Professional jockeys are unique amongst weight-making athletes given that they
      face the requirement to make weight daily. Furthermore, unlike other weight
      limited sports, jockeys who have engaged in rapid weight loss cannot fully
      rehydrate prior to competition because post-race weight must not be more than 1
      kg different to their pre-race weight. As such, jockeys have reported a variety
      of acute and chronic methods to make weight that include sporadic eating, caloric
      restriction, diuretics, laxatives, vomiting and fluid restriction as well as
      regular use of sweat suits and saunas. Typical daily energy intake is reported to
      be 6.5-8.0 MJ (carbohydrate 3 g kg(-1) body weight, fat 1 g kg(-1) body weight,
      protein 1 g kg(-1) body weight) and jockeys also exhibit micronutrient
      deficiencies that include vitamin D and calcium. Accordingly, the combination of
      low macronutrient, micronutrient and fluid intake results in poor bone health and
      abnormal mood profiles and can also impair simulated riding performance. Although
      the energy cost of real-world training and racing is unknown, energy expenditure
      during simulated race riding and total daily energy expenditure was 0.20 and 11.0
      MJ, respectively. Such estimates of energy expenditure are considerably lower
      than that of other sports and suggest that conventional sports nutrition
      guidelines may not be applicable to the elite jockey. Furthermore, the use of
      daily diets that emphasise a high-protein and reduced carbohydrate intake (in the
      form of six small daily meals) in combination with structured exercise has also
      proven effective in reducing body mass and maintaining target racing weight. In
      this regard, available data suggest the need for those organisations responsible
      for jockey welfare to implement widespread educational programmes to assist in
      improving both the physical and mental well-being of professional jockeys. Given
      the high occupational risks associated with race riding (e.g. falls and bone
      fractures), future research should specifically target strategies to improve bone
      health through the use of structured weight-bearing exercise and correcting
      nutritional deficiencies. 

PMID- 24682949
TI  - What is normal? Female lower limb kinematic profiles during athletic tasks used
      to examine anterior cruciate ligament injury risk: a systematic review.
AB  - BACKGROUND: It has been proposed that the performance of athletic tasks where
      normal motion is exceeded has the potential to damage the anterior cruciate
      ligament (ACL). Determining the expected or 'normal' kinematic profile of
      athletic tasks commonly used to assess ACL injury risk can provide an evidence
      base for the identification of abnormal or anomalous task performances in a
      laboratory setting. OBJECTIVE: The objective was to conduct a systematic review
      of studies examining lower limb kinematics of females during drop landing, drop
      vertical jump, and side-step cutting tasks, to determine 'normal' ranges for hip
      and knee joint kinematic variables. DATA SOURCES: An electronic database search
      was conducted on the SPORTDiscus(TM), MEDLINE, AMED and CINAHL (January 1980
      August 2013) databases using a combination of relevant keywords. STUDY SELECTION:
      Studies identified as potentially relevant were independently examined by two
      reviewers for inclusion. Where consensus could not be reached, a third reviewer
      was consulted. Original research articles that examined three-dimensional hip and
      knee kinematics of female subjects during the athletic tasks of interest were
      included for review. Articles were excluded if subjects had a history of lower
      back or lower limb joint injury or isolated data from the female cohort could not
      be extracted. STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently
      assessed the quality of included studies. Data on subject characteristics, the
      athletic task performed, and kinematic data were extracted from included studies.
      Studies were categorised according to the athletic task being examined and each
      study allocated a weight within categories based on the number of subjects
      assessed. Extracted data were used to calculate the weighted means and standard
      deviations for hip and knee kinematics (initial contact and peak values).
      'Normal' motion was classified as the weighted mean plus/minus one standard
      deviation. RESULTS: Of 2,920 citations, a total of 159 articles were identified
      as potentially relevant, with 29 meeting all inclusion/exclusion criteria. Due to
      the limited number of studies available examining double-leg drop landings and
      single-leg drop vertical jumps, insufficient data was available to include these
      tasks in the review. Therefore, a total of 25 articles were included. From the
      included studies, 'normal' ranges were calculated for the kinematic variables of
      interest across the athletic tasks examined. LIMITATIONS: Joint forces and other
      additional elements play a role in ACL injuries, therefore, focusing solely on
      lower limb kinematics in classifying injury risk may not encapsulate all relevant
      factors. Insufficient data resulted in no normal ranges being calculated for
      double-leg drop land and single-leg drop vertical jump tasks. No included study
      examined hip internal/external rotation during single-leg drop landings,
      therefore ranges for this kinematic variable could not be determined. Variation
      in data between studies resulted in wide normal ranges being observed across
      certain kinematic variables. CONCLUSIONS: The ranges calculated in this review
      provide evidence-based values that can be used to identify abnormal or anomalous
      athletic task performances on a multi-planar scale. This may be useful in
      identifying neuromuscular factors or specific muscular recruitment strategies
      that contribute to ACL injury risk.

PMID- 24682952
TI  - MiR-203 is downregulated in laryngeal squamous cell carcinoma and can suppress
      proliferation and induce apoptosis of tumours.
AB  - MicroRNAs (miRNAs) have been recognised to regulate cancer development and
      progression in carcinogenesis as either oncogenes or tumour suppressor genes.
      However, whether miR-203 plays a crucial role in human laryngeal squamous cell
      carcinoma (LSCC) remains largely unclear. In the study, we have found that miR
      203 expression was significantly lower in LSCC tissues than that in corresponding
      adjacent non-neoplastic tissues and was negatively correlated with ASAP1
      expression level. Lower expression of miR-203 was significantly related to poor
      differentiation, advanced clinical stages, T3-4 tumour grade, lymph node
      metastasis and decreased 5-year overall survival. Transfection with miR-203
      inhibited proliferation, reduced invasion, induced apoptosis and caused G1 phase
      cell cycle arrest of Hep-2 cells in vitro, suggesting that miR-203 functioned as
      a tumour suppressor. We have also tested that over-expression of miR-203 may both
      suppress the growth of xenograft tumours in mice and downregulate the expressions
      of ASAP1 in vivo. Furthermore, miR-203 may regulate the expressions of
      mesenchymal transition (EMT) marker of E-cadherin and cancer stem cells (CSCs)
      marker of CD44. These findings suggest that miR-203 plays a role as a tumour
      suppressor in LSCC, likely by regulating ASAP1, probably in relation to EMT and
      CSCs and may serve as a potential target for therapeutic intervention. 

PMID- 24682953
TI  - GSTM1 polymorphism and lung cancer risk among East Asian populations: a meta
      analysis.
AB  - GSTM1 gene encodes a key enzyme involved in the metabolism of xenobiotics, and
      its polymorphisms have been related to individual susceptibility to several
      malignancies. Many molecular epidemiological studies were performed to
      investigate the association between the GSTM1 null polymorphism and lung cancer
      susceptibility in East Asia. However, the results were inconsistent. In order to
      derive a more precise estimation, we conducted this meta-analysis involving 5,909
      lung cancer cases and 7,067 controls from 35 studies. We used crude odds ratios
      (ORs) with 95 % confidence intervals (CIs) to assess the association between
      GSTM1 null genotype and the risk of lung cancer. Our study found that the GSTM1
      null genotype appeared to be a significant risk factor for lung cancer in East
      Asia population (OR = 1.30, 95 % CI = 1.17-1.45, P heterogeneity < 0.0001, and I
      (2) = 54.0 %).

PMID- 24682955
TI  - Giant left atrial appendage aneurysm.

PMID- 24682954
TI  - Effect of chemical and metallic compounds on biomass, mRNA levels and laccase
      activity of Phlebia brevispora BAFC 633.
AB  - Nine aromatic compounds (caffeic acid, syringaldehyde, vanillic acid, guaiacol,
      vanillin, sinapic acid, syringol, syringic acid and ferulic acid) and four
      metallic compounds (CuSO4, AgNO3, MnSO4, and CaCl2) were tested for their ability
      to increase laccase (Lac) activity in the ligninolytic basidiomycete Phlebia
      brevispora BAFC 633. The addition of syringaldehyde, syringol, guaiacol, sinapic
      acid, vanillin, ferulic acid and CuSO4 showed a positive effect on fungal growth;
      however, it decreased dramatically with the addition of AgNO3 and did not undergo
      changes in the presence of CaCl2 or MnSO4. Lac activity increased with the
      addition of all the compounds tested, depending on the concentration and the day
      of culture. P. brevispora BAFC 633 produced two isoenzymes, a constitutively
      expressed of 60 kDa and another of 75 kDa expressed upon induction by sinapic
      acid, MnSO4 or CuSO4. Lac secretion capacity of P. brevispora BAFC 633 can be
      increased 27 times higher than the control with the highest levels detected in
      the presence of 0.3 mM CuSO4 at day 14. The action is affected at pre
      transcriptional level regulating at the onset of the process, however it does not
      rule out the effect at the post-transcriptional and post-translational levels,
      for which is necessary to deepen in the knowledge of all possible regulation
      points of gene expression.

PMID- 24682956
TI  - Synchronicity of echocardiography and cardiac nuclear medicine in mid-ventricular
      ballooning syndrome: paired 'ring signs' on polar maps.

PMID- 24682957
TI  - Amplatzer(r) septal occluder device early embolization to left ventricular
      outflow tract in asymptomatic patient.

PMID- 24682958
TI  - Sex differences in the developmental trajectories of impulse control and
      sensation-seeking from early adolescence to early adulthood.
AB  - It has been proposed that high rates of risk-taking in adolescence are partly
      attributable to patterns of neurobiological development that promote an increase
      in sensation-seeking tendencies at a time when impulse control is still
      developing. It is not known, however, whether this pattern is the same for males
      and females. The present study investigates sex differences in the developmental
      trajectories of self-reported impulse control and sensation-seeking between the
      ages of 10 and 25 using longitudinal data from the National Longitudinal Study of
      Youth 1979 Child and Young Adult Survey (N = 8,270; 49% female; 33% Black, 22%
      Hispanic, 45% Non-Black, Non-Hispanic). Prior work has found that, consistent
      with the dual-systems model of adolescent neurobiological development, sensation
      seeking rises and falls across this age span, whereas impulse control increases
      into the 20s. In the present study, we find that this same general pattern holds
      for both males and females, but with some key differences. As expected, males
      exhibit higher levels of sensation-seeking and lower levels of impulse control
      than females. Differences also emerged in the shapes of the developmental
      trajectories. Females reach peak levels of sensation-seeking earlier than males
      (consistent with the idea that sensation-seeking is linked to pubertal
      development) and decline in sensation-seeking more rapidly thereafter. Also,
      males increase in impulse control more gradually than females. Consequently, sex
      differences in both impulse control and sensation-seeking increase with age. The
      findings suggest that the window of heightened vulnerability to risk-taking
      during adolescence may be greater in magnitude and more protracted for males than
      for females.

PMID- 24682959
TI  - Non-suicidal self-injury and firesetting: shared and unique correlates among
      school-based adolescents.
AB  - Distinct behaviors such as non-suicidal self-injury (NSSI) and firesetting may
      represent functionally equivalent attempts to regulate difficult
      affective/cognitive or social experiences during adolescence. This study examined
      possible mechanisms leading to NSSI, as opposed to firesetting, as well as co
      occurrence of these behaviors. Participants aged 12-18 years (N = 2,356; 67.5 %
      female) completed self-report questionnaires measuring NSSI and firesetting, as
      well as socio-demographic and psychosocial factors including personality traits
      related to impulsivity and anxiety, negative life events, emotion regulation, and
      coping. The findings indicated the presence of general risk factors (e.g.,
      negative life events and poor coping) that increase the likelihood that
      adolescents will engage in any of a range of maladaptive behaviors. The
      probability of at-risk adolescents engaging in NSSI was increased by
      psychological states (i.e., rumination and poor self-esteem), whereas socio
      demographic and personality traits were associated with firesetting. Implications
      for prevention and early intervention initiatives are discussed.

PMID- 24682960
TI  - The effects of ethnic/racial discrimination and sleep quality on depressive
      symptoms and self-esteem trajectories among diverse adolescents.
AB  - Ethnic/racial discrimination has persistent negative implications for both
      physical and mental health. The current study employs a risk and resilience
      framework to explore the joint effects of ethnic/racial discrimination and sleep
      disturbance on psychosocial outcomes among adolescents. In a sample of 146
      minority and White adolescents (70% female), changes in depressive symptoms,
      anxiety, and self-esteem over 3 years are explored using growth curve models.
      Regardless of ethnic background, adolescents reporting high levels of
      ethnic/racial discrimination and poor sleep also reported a corresponding
      increase in depressive symptoms and lower levels of self-esteem over time.
      Adolescents reporting all other combinations of sleep quality and ethnic/racial
      discrimination reported more positive adjustment over time. The joint effects of
      sleep and ethnic/racial discrimination on adolescent psychosocial development are
      discussed.

PMID- 24682961
TI  - Characterization of RNA binding protein RBP-P reveals a possible role in rice
      glutelin gene expression and RNA localization.
AB  - RNA binding proteins (RBPs) play an important role in mRNA metabolism including
      synthesis, maturation, transport, localization, and stability. In developing rice
      seeds, RNAs that code for the major storage proteins are transported to specific
      domains of the cortical endoplasmic reticulum (ER) by a regulated mechanism
      requiring RNA cis-localization elements, or zipcodes. Putative trans-acting RBPs
      that recognize prolamine RNA zipcodes required for restricted localization to
      protein body-ER have previously been identified. Here, we describe the
      identification of RBP-P using a Northwestern blot approach as an RBP that
      recognizes and binds to glutelin zipcode RNA, which is required for proper RNA
      localization to cisternal-ER. RBP-P protein expression coincides with that of
      glutelin during seed maturation and is localized to both the nucleus and cytosol.
      RNA-immunoprecipitation and subsequent RT-PCR analysis further demonstrated that
      RBP-P interacts with glutelin RNAs. In vitro RNA-protein UV-crosslinking assays
      showed that recombinant RBP-P binds strongly to glutelin mRNA, and in particular,
      3' UTR and zipcode RNA. RBP-P also exhibited strong binding activity to a
      glutelin intron sequence, suggesting that RBP-P might participate in mRNA
      splicing. Overall, these results support a multifunctional role for RBP-P in
      glutelin mRNA metabolism, perhaps in nuclear pre-mRNA splicing and cytosolic
      localization to the cisternal-ER. 

PMID- 24682962
TI  - The effect of myocardial infarct size on cardiac reserve in rhesus monkeys.
AB  - Evaluation of cardiac reserve under myocardial infarction in patients is
      important for prognosis. However, this evaluation is difficult to be done due to
      high risk for mortality in patients with severe myocardial infarction. The
      present study was undertaken using non-human primate model as a substitute for
      humans to investigate the relationship between cardiac reserve and myocardial
      infarct size. Rhesus monkeys of 2-3 years old (n = 27) were subjected to left
      anterior descending artery ligation to introduce acute myocardial infarction. By
      altering the ligation position along the artery, varying sizes of myocardial
      infarction were generated, from 20 to 58 % of the total myocardium mass. These
      subjects were divided into 4 groups based on the infarct size: below 25 %,
      between 25 and 35 %, between 35 and 45 %, and above 45 % of the total mass.
      Changes in cardiac contractility were determined by echocardiography along with
      the development of myocardial infarction, and by invasive hemodynamic measurement
      at the end of the experiment. Correlation analysis revealed that hearts with
      infarct sizes <25 % of the total mass fully responded to the increase in the load
      generated by heart rate escalation. Hearts with infarct sizes between 25 and 45 %
      responded the load increase with gradient decline in the maximum contractility.
      Hearts with infarct sizes more than 45 % failed to respond to the increase in the
      load. Therefore, we consider myocardial infarct size <25 % of the total mass as
      compensable injury, between 25 and 45 % as depleting injury, and more than 45 %
      as exhausted injury with regard to cardiac reserve. This would serve as a
      surrogate model for patients with myocardial infarction. 

PMID- 24682964
TI  - Prevalence of idiopathic normal-pressure hydrocephalus.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of idiopathic
      normal-pressure hydrocephalus (iNPH) in elderly persons in a large population
      based sample using radiologic and clinical examinations. METHODS: We examined
      representative elderly populations aged 70 years and older that had undergone
      neuropsychiatric evaluations and CT of the brain between 1986 and 2000 (n =
      1,238). Gait was evaluated by clinical examination and history of walking
      difficulty. Cognitive function was evaluated with the Mini-Mental State
      Examination and urinary incontinence by self-report. iNPH was diagnosed in
      concordance with the American-European iNPH guidelines. Exclusion criteria were
      history of meningitis, severe head trauma, and subarachnoid hemorrhage. RESULTS:
      The prevalence of probable iNPH was 0.2% in those aged 70-79 years (n = 2) and
      5.9% (n = 24) in those aged 80 years and older, with no difference between men
      and women. Only 2 of these persons had been treated for iNPH. Hydrocephalic
      ventricular enlargement, i.e., a CT image consistent with NPH, was found in 56
      persons (4.5%). An Evans Index >0.3 was found in 256 (20.7%) and occluded sulci
      at the high convexity in 67 persons (5.4%). All of these findings were more
      common in the older age groups. CONCLUSIONS: Many elderly possess clinical and
      imaging features of iNPH, especially those older than 80 years. The number of
      persons with iNPH is probably much higher than the number of persons currently
      treated.

PMID- 24682965
TI  - Modifiable cardiovascular risk factors and axial motor impairments in Parkinson
      disease.
AB  - OBJECTIVE: Cardiovascular comorbidities associate with neurodegeneration in the
      elderly and may contribute to extranigral pathologies and medically refractory
      axial motor features in Parkinson disease (PD). METHODS: We explored differences
      in the estimated rate of axial motor feature accrual between patients with PD
      with and without elevated cardiovascular risk factors as estimated by the
      Framingham General Cardiovascular Disease risk-scoring algorithm in a cross
      sectional cohort study. All participants underwent motor evaluations with the
      Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS
      UPDRS), [(11)C]dihydrotetrabenazine (DTBZ) monoaminergic brain PET imaging, and
      MRI. RESULTS: Participants with PD with elevated Framingham risk (FR) scores (n =
      63, 74.1%) showed higher unadjusted rates of total MDS-UPDRS (t = 3.60, p =
      0.0006) and axial motor scores (t = 3.98, p = 0.0001) per estimated year of motor
      symptoms compared to participants with normal-range risk scores (n = 22, 25.9%).
      After controlling for sex, Montreal Cognitive Assessment score, frontal
      leukoaraiosis severity, and striatal DTBZ activity, elevated risk factor status
      was associated with the rate of accrual of axial motor impairments (R(2) = 0.206;
      t = 2.62, p = 0.011) but not with total MDS-UPDRS motor score (R(2) = 0.198; t =
      1.51, p = 0.135). Frontal leukoaraiosis was associated with the rate of axial and
      total MDS-UPDRS scores per year of symptoms and also with elevated systolic blood
      pressure (R(2) = 0.291; t = 2.30, p = 0.024) in a separate risk-factor model.
      CONCLUSION: Cardiovascular risk factors may contribute to axial motor features in
      PD. Early modification of cardiovascular risk factors, including hypertension,
      deserves further study as a novel disease-modifying strategy in PD.

PMID- 24682966
TI  - MS disease activity in RESTORE: a randomized 24-week natalizumab treatment
      interruption study.
AB  - OBJECTIVE: RESTORE was a randomized, partially placebo-controlled exploratory
      study evaluating multiple sclerosis (MS) disease activity during a 24-week
      interruption of natalizumab. METHODS: Eligible patients were relapse-free through
      the prior year on natalizumab and had no gadolinium-enhancing lesions on
      screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to
      switch to placebo, or to receive alternative immunomodulatory therapy (other
      therapies: IM interferon beta-1a [IM IFN-beta-1a], glatiramer acetate [GA], or
      methylprednisolone [MP]). During the 24-week randomized treatment period,
      patients underwent clinical and MRI assessments every 4 weeks. RESULTS: Patients
      (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other
      therapies (n = 88: IM IFN-beta-1a, n = 17; GA, n = 17; MP, n = 54). Of 167
      patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence:
      0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-beta-1a, 8/15 (53%)
      GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%
      29% of patients in the other treatment arms. MRI disease activity recurred
      starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as
      4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167
      patients (30%), all in placebo or other-therapies groups, restarted natalizumab
      early because of disease activity. CONCLUSIONS: MRI and clinical disease activity
      recurred in some patients during natalizumab interruption, despite use of other
      therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that
      for patients with MS taking natalizumab who are relapse-free for 1 year, stopping
      natalizumab increases the risk of MS relapse or MRI disease activity as compared
      with continuing natalizumab.

PMID- 24682968
TI  - Natalizumab discontinuation in the increasing complexity of multiple sclerosis
      therapy.

PMID- 24682967
TI  - Chronic meralgia paresthetica and neurectomy: a clinical pathologic study.
AB  - OBJECTIVE: To understand the pathologic and clinical correlates of patients with
      chronic meralgia paresthetica (MP) undergoing lateral femoral cutaneous nerve
      (LFCN) neurectomy. METHODS: A retrospective cohort approach was utilized to
      identify 7 patients undergoing LFCN neurectomy for intractable pain. Control
      autopsied LFCN was obtained. Clinical, radiologic, and electrophysiologic
      features were reviewed. RESULTS: In identified cases, preoperative symptoms
      included severe lateral thigh pain and numbness. The duration of symptoms prior
      to surgery ranged from 2 to 15 years. Body mass index (BMI) varied from 20
      kg/m(2) to 44.8 kg/m(2) (normal-morbidly obese), with 6 out of 7 patients being
      obese. No patients were diabetic. Focal nerve indentation at the inguinal
      ligament was seen intraoperatively and on gross pathology in 4 of 7 cases.
      Multifocal fiber loss, selective loss of large myelinated fibers, thinly
      myelinated profiles, regenerating nerve clusters, perineurial thickening, and
      subperineurial edema were seen. None of these features were observed in control
      nerve. Morphometric analysis confirmed loss of large myelinated fibers with small
      and intermediate size fiber predominance. Five patients had varying degrees of
      intraneural and epineurial inflammation. Six of 7 reported improved pain after
      neurectomy, sometimes dramatic. CONCLUSIONS: Patients with chronic MP and
      intractable pain have an LFCN mononeuropathy with loss of nerve fibers.
      Pathologic and clinical study supports a compressive pathogenesis as the primary
      mechanism. Abnormal nerve inflammation coexists and may play a role in
      pathogenesis. These selected patients typically benefited from neurectomy at a
      site of inguinal ligament compression. CLASSIFICATION OF EVIDENCE: This study
      provides Class IV evidence that patients with chronic MP LFCN neurectomy
      experience improvement in MP-related pain.

PMID- 24682969
TI  - Seoul criteria for PiB(-) subcortical vascular dementia based on clinical and MRI
      variables.
AB  - OBJECTIVE: The purpose of this study was to propose new criteria for
      differentiating Pittsburgh compound B (PiB)-negative from PiB-positive
      subcortical vascular dementia (SVaD) using clinical and MRI variables. METHODS:
      We measured brain amyloid deposition using PiB-PET in 77 patients with SVaD. All
      patients met DSM-IV criteria for vascular dementia and had severe white matter
      hyperintensities on MRI, defined as a cap or band >= 10 mm as well as a deep
      white matter lesion >= 25 mm. Eleven models were considered to differentiate PiB(
      ) from PiB(+) SVaD using 4 variables, including age, number of lacunes, medial
      temporal atrophy (MTA), and APOE epsilon4. The ideal cutoff values in each of the
      11 models were selected using the highest Youden index. RESULTS: A total of 49 of
      77 patients (63.6%) tested negative for PiB retention, while 28 (36.4%) tested
      positive for PiB retention. The ideal model for differentiating PiB(-) from
      PiB(+) SVaD was as follows: age <= 75 years, >= 5 lacunes, and MTA <= 3, which
      together yielded an accuracy of 67.5%. CONCLUSION: When patients meet the DSM-IV
      criteria for vascular dementia and also have severe white matter
      hyperintensities, younger age, greater number of lacunes, and lesser MTA, these
      are predictive of a PiB(-) scan in patients with SVaD. CLASSIFICATION OF
      EVIDENCE: This study provides Class II evidence that the combination of younger
      age, greater number of lacunes, and lesser MTA identifies patients with SVaD at
      lower risk of Alzheimer disease pathology.

PMID- 24682970
TI  - Dementia and dependence: do modifiable risk factors delay disability?
AB  - OBJECTIVE: To identify modifying factors that preserve functional independence
      among individuals at high dementia risk. METHODS: Health and Retirement Study
      participants aged 65 years or older without baseline activities of daily living
      (ADL) limitations (n = 4,922) were interviewed biennially for up to 12 years.
      Dementia probability, estimated from direct and proxy cognitive assessments, was
      categorized as low (i.e., normal cognitive function), mild, moderate, or high
      risk (i.e., very impaired) and used to predict incident ADL limitations
      (censoring after limitation onset). We assessed multiplicative and additive
      interactions of dementia category with modifiers (previously self-reported
      physical activity, smoking, alcohol consumption, depression, and income) in
      predicting incident limitations. RESULTS: Smoking, not drinking, and income
      predicted incident ADL limitations and had larger absolute effects on ADL onset
      among individuals with high dementia probability than among cognitively normal
      individuals. Smoking increased the 2-year risk of ADL limitations onset from 9.9%
      to 14.9% among the lowest dementia probability category and from 32.6% to 42.7%
      among the highest dementia probability category. Not drinking increased the 2
      year risk of ADL limitations onset by 2.1 percentage points among the lowest
      dementia probability category and 13.2 percentage points among the highest
      dementia probability category. Low income increased the 2-year risk of ADL
      limitations onset by 0.4% among the lowest dementia probability category and
      12.9% among the highest dementia probability category. CONCLUSIONS: Smoking, not
      drinking, and low income predict incident dependence even in the context of
      cognitive impairment. Regardless of cognitive status, reducing these risk factors
      may improve functional outcomes and delay institutionalization.

PMID- 24682971
TI  - Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS.
AB  - OBJECTIVE: To elucidate the neuropathology in cerebellar ataxia with neuropathy
      and bilateral vestibular areflexia syndrome (CANVAS), a novel cerebellar ataxia
      comprised of the triad of cerebellar impairment, bilateral vestibular
      hypofunction, and a peripheral sensory deficit. METHOD: Brain and spinal
      neuropathology in 2 patients with CANVAS, together with brain and otopathology in
      another patient with CANVAS, were examined postmortem. RESULTS: Spinal cord
      pathology demonstrated a marked dorsal root ganglionopathy with secondary tract
      degeneration. Cerebellar pathology showed loss of Purkinje cells, predominantly
      in the vermis. CONCLUSION: The likely underlying sensory pathology in CANVAS is
      loss of neurons from the dorsal root and V, VII, and VIII cranial nerve ganglia
      in other words, it is a "neuronopathy" rather than a "neuropathy." Clinically,
      CANVAS is a differential diagnosis for both spinocerebellar ataxia type 3 (or
      Machado-Joseph disease) and Friedreich ataxia. In addition, there are 6 sets of
      sibling pairs, implying that CANVAS is likely to be a late-onset recessive or
      autosomal dominant with reduced penetrance disorder, and identification of the
      culprit gene is currently a target of investigation.

PMID- 24682972
TI  - Can fall of blood pressure prevent falls in Parkinson disease?

PMID- 24682973
TI  - Natalizumab in progressive MS: results of an open-label, phase 2A, proof-of
      concept trial.
AB  - OBJECTIVE: Natalizumab inhibits the migration of systemic immune cells to the CNS
      and may be beneficial in progressive multiple sclerosis (MS). The objective of
      the study was to examine the effects of natalizumab in progressive MS. METHODS:
      In an open-label phase 2A study, 24 patients with progressive MS were included to
      receive natalizumab treatment for 60 weeks. Response to natalizumab was assessed
      in CSF and MRI studies. The primary endpoint was change in CSF osteopontin, a
      biomarker of intrathecal inflammation, from baseline to week 60. RESULTS:
      Seventeen patients completed the study. No new safety issues were encountered.
      CSF osteopontin decreased by 65 ng/mL (95% confidence interval 34-96 ng/mL; p =
      0.0004) from baseline to week 60 in conjunction with decreases in other CSF
      biomarkers of inflammation, axonal damage, and demyelination. Magnetization
      transfer ratio increased in both cortical gray and normal-appearing white matter
      and correlated with decreases in CSF neurofilament light chain. CONCLUSIONS:
      Natalizumab treatment of progressive MS reduces intrathecal inflammation and
      tissue damage, supporting a beneficial effect of natalizumab treatment in
      progressive MS and suggesting that systemic inflammation contributes to the
      pathogenesis. Moreover, the study establishes the feasibility of using CSF
      biomarkers in proof-of-concept trials, allowing a low number of participants and
      short study duration. CLASSIFICATION OF EVIDENCE: This study provides Class IV
      evidence that in patients with progressive MS, natalizumab reduces biomarkers of
      intrathecal inflammation.

PMID- 24682975
TI  - Randomized study of placebo and framing information in direct-to-consumer print
      advertisements for prescription drugs.
AB  - BACKGROUND: Research suggests that quantitative information in direct-to-consumer
      (DTC) prescription drug ads may be helpful for consumers. PURPOSE: The objective
      was to examine the effect of adding placebo rates and framing to DTC ads.
      METHODS: In study 1, 2,000 Internet panel members with chronic pain participated
      in a randomized controlled experiment of DTC ads varying in placebo rate and
      framing. In study 2, 596 physicians ranked DTC ads varying in placebo rate and
      framing by how well they conveyed scientific information and their usefulness for
      patients. RESULTS: In study 1, participants who viewed placebo rates were able to
      recall them and use them to form certain perceptions. A mixed frame led to lower
      placebo rate recall and perceived efficacy. In study 2, overall, physicians
      preferred a placebo/single frame ad. CONCLUSIONS: Adding placebo rates to DTC ads
      may be useful for consumers. The evidence does not support using a mixed frame.

PMID- 24682974
TI  - Integrated extracellular matrix signaling in mammary gland development and breast
      cancer progression.
AB  - Extracellular matrix (ECM), a major component of the cellular microenvironment,
      plays critical roles in normal tissue morphogenesis and disease progression.
      Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain
      receptors, and dystroglycan, elicits biochemical and biomechanical signals that
      control cellular architecture and gene expression. These ECM signals cooperate
      with growth factors and hormones to regulate cell migration, differentiation, and
      transformation. ECM signaling is tightly regulated during normal mammary gland
      development. Deposition and alignment of fibrillar collagens direct migration and
      invasion of mammary epithelial cells during branching morphogenesis. Basement
      membrane proteins are required for polarized acinar morphogenesis and milk
      protein expression. Deregulation of ECM proteins in the long run is sufficient to
      promote breast cancer development and progression. Recent studies demonstrate
      that the integrated biophysical and biochemical signals from ECM and soluble
      factors are crucial for normal mammary gland development as well as breast cancer
      progression.

PMID- 24682976
TI  - Expanded-ring N-heterocyclic carbenes efficiently stabilize gold(I) cations,
      leading to high activity in pi-acid-catalyzed cyclizations.
AB  - A series of six- and seven-membered expanded-ring N-heterocyclic carbene (er-NHC)
      gold(I) complexes has been synthesized using different synthetic approaches.
      Complexes with weakly coordinating anions [(er-NHC)AuX] (X(-) = BF4(-), NTf2(-),
      OTf(-)) were generated in solution. According to their (13)C NMR spectra, the
      ionic character of the complexes increases in the order X(-) = Cl(-) < NTf2(-) <
      OTf(-) < BF4(-). Additional factors for stabilization of the cationic complexes
      are expansion of the NHC ring and the attachment of bulky substituents at the
      nitrogen atoms. These er-NHCs are bulkier ligands and stronger electron donors
      than conventional NHCs as well as phosphines and sulfides and provide more
      stabilization of [(L)Au(+)] cations. A comparative study has been carried out of
      the catalytic activities of five-, six-, and seven-membered carbene complexes
      [(NHC)AuX], [(Ph3 P)AuX], [(Me2S)AuX], and inorganic compounds of gold in model
      reactions of indole and benzofuran synthesis. It was found that increased ionic
      character of the complexes was correlated with increased catalytic activity in
      the cyclization reactions. As a result, we developed an unprecedentedly active
      monoligand cationic [(THD-Dipp)Au]BF4 (1,3-bis(2,6-diisopropylphenyl)-3,4,5,6
      tetrahydrodiazepin-2-ylidene gold(I) tetrafluoroborate) catalyst bearing seven
      membered-ring carbene and bulky Dipp substituents. Quantitative yields of
      cyclized products were attained in several minutes at room temperature at 1 mol %
      catalyst loadings. The experimental observations were rationalized and fully
      supported by DFT calculations.

PMID- 24682977
TI  - Structural optimization and biological screening of a steroidal scaffold
      possessing cucurbitacin-like functionalities as B-Raf inhibitors.
AB  - Inhibition of the mitogen-activated protein kinase (MAPK) pathway by targeting
      the commonly occurring mutated B-Raf in melanoma has become a practical method
      for the development of drugs and drug candidates. In order to expand upon the
      currently reported structural scaffolds used to target the MAPK pathway,
      molecular docking studies led to the installation an alpha,beta-unsaturated
      ketone side chain, related to the cucurbitacin class of natural products, on to
      an estrone core via an aldol condensation reaction, along with installation of
      the Delta(9,11) olefin to assemble what has been defined as a pseudo-cis
      configuration at the B/C ring juncture. Combination of these cucurbitacin-like
      features resulted in a compound with an enhanced biological profile against the A
      375 mutant B-Raf cell line, in regards to their cytotoxicity and inhibitory
      activity toward phosphorylated extracellular-signal-regulated kinase (ERK). 

PMID- 24682979
TI  - Pain catastrophizing and employment histories.
AB  - BACKGROUND: Studies examining pain catastrophizing and employment have had mixed
      findings. No study of pain catastrophizing has examined its relationship to
      lifetime employment status in a general clinical population. AIMS: To examine
      pain catastrophizing in relationship to lifetime employment functioning in a
      sample of US primary care patients (rather than injured workers). METHODS: A
      cross-sectional anonymous self-report survey of consecutive adults in a US
      internal medicine outpatient clinic. We assessed pain catastrophizing using the
      Pain Catastrophizing Scale and employment histories using a four-item author
      developed measure. RESULTS: There were 239 participants and an initial
      participation rate of 70%. While pain catastrophizing was not related to the
      number of different full-time jobs held or the percentage of time employed in
      adulthood, pain catastrophizing was statistically significantly associated with
      ever having been paid 'under the table' [F(1,236) = 27.89, P < 0.001] and ever
      having been fired from a job [F(1,237) = 50.78, P < 0.001], as well as with not
      getting along with fellow employees [F(1,60) = 7.48, P < 0.01]. CONCLUSIONS: In
      this clinical sample, pain catastrophizing demonstrated varying relationships
      with different aspects of lifetime employment, rather than exerting an overall
      global effect on employment.

PMID- 24682980
TI  - New polymorphisms in the novel LYRM1 gene are associated with body measurement
      and meat quality traits in Qinchuan cattle.
AB  - Body measurement and meat quality traits play important roles in the evaluation
      of productivity in cattle; they are influenced by genetic and environmental
      factors. Recent studies have shown that LYRM1 is a novel gene related to obesity
      and may influence fat deposition. We screened for new polymorphisms in the bovine
      LYRM1 gene and analyzed their association with body measurement and meat quality
      traits in cattle. DNA samples were obtained from 572 Qinchuan cattle aged from 18
      to 24 months. DNA sequencing was used to find the LYRM1 single nucleotide
      polymorphisms (SNPs). Sequence analysis of LYRM1 revealed four novel SNPs in exon
      3: G50A in coding region, C126A, A127T, and T128A in a 3'-untranslated region.
      G50A, A127T and T128A showed two genotypes: AG and GG, AA and AT, AT and TT,
      respectively; while C126A showed three genotypes: AA, AC and CC. Analysis showed
      that these four polymorphisms were significantly associated with body measurement
      and meat quality traits in the Qinchuan cattle population. We suggest that the
      LYRM1 gene can be used for marker-assisted selection to improve body measurement
      and meat quality traits in the Qinchuan cattle population. 

PMID- 24682981
TI  - Clinical retrospective analysis of cases with multiple primary malignant
      neoplasms.
AB  - The etiological factors, clinical characteristics, diagnosis, treatment
      strategies, and prognosis of multiple primary malignant neoplasms (MPMNs) were
      investigated in order to improve its diagnosis and therapy. Clinical data of 170
      patients with MPMN who were admitted to the Oncology Department of the First
      Affiliated Hospital of Anhui Medical University from January 2004 to April 2010
      were collected and analyzed retrospectively. The overall incidence of MPMNs was
      2.25%. There were 167 cases with duplex primary cancers, 2 cases with triple
      primary cancers, 1 case with quadruple primary cancer, 46 synchronous MPMNs
      (SMPMNs), and 124 metachronous MPMNs (MMPMNs). There were 344 malignant neoplasms
      in the 170 MPMN patients, of which 161 were in the alimentary system, 48 in the
      respiratory system, 63 in mammary glands, 30 in the genital system, 7 in the
      urinary system, 23 in the head and neck, and the other 12 were in the brain,
      hematological system, and soft tissue. There were 22 cases of bilateral primary
      breast cancer and 41 cases of digestive MPMN. With a median survival time of 24
      months, the 1-, 3-, and 5-year cumulative survival rates in the 170 patients were
      68.8, 39.1, and 25.2%, respectively. The most common locations of MPMN were the
      alimentary system, mammary gland, and respiratory system. MPMN usually occurred
      in distinct organs of identical systems, conjugate organs, or identical organs.
      The survival rate of SMPMN was similar to that of MMPMN. There were differences
      in principles of treatment and diagnosis between MPMN and metastasis or recurrent
      cancers. 

PMID- 24682982
TI  - Molecular cloning and cDNA characterization of Camelus dromedarius putative
      cytochrome P450s 1A, 2C, and 3A.
AB  - The domesticated one-humped Arabian camel, Camelus dromedarius, is one of the
      most important animals in the Arabian Peninsula. Most of its life, this animal is
      exposed to both intrinsic and extrinsic genotoxic factors that are known to cause
      gross metabolic alterations in many organisms. This study determined the full
      length coding sequence of 3 cytochrome P450s cDNAs; namely, CYP450 1A1, CYP450 2C
      and CYP450 3A using reverse transcription polymerase chain reaction. The C.
      dromedarius CYP450s 1A1, 2C, and 3A have open reading frames of 1563, 1473, and
      1566 bp and cDNAs that encode proteins of 520, 490, and 521 amino acid residues,
      respectively. The molecular weights calculated for CYP1A1, 2C, and 3A were found
      to be 58.651, 56.03, and 58.594 kDa, while the predicted calculated isoelectric
      points using a computer algorithm were 7.315, 6.579, and 9.46. The deduced amino
      acid sequences of these CYPs showed the membrane anchored signal peptide, the
      conserved proline-rich amino terminus and the characteristic heme-binding
      signature localized near the carboxy terminus of the protein. 

PMID- 24682983
TI  - Transcriptome profiling of the crofton weed gall fly Procecidochares utilis.
AB  - Procecidochares utilis is a tephritid gall fly, which is known to be an effective
      biological agent that can be used to control the notoriously widespread crofton
      weed Eupatorium adenophorum. Despite its importance, genetic resources for P.
      utilis remain scarce. In this study, 1.2 Gb sequences were generated using
      Illumina paired-end sequencing technology. De novo assemblies yielded 491,760
      contigs, 90,474 scaffolds, and 58,562 unigenes. Among the unigenes, 34,809
      (59.44%) had a homologous match against the National Center for Biotechnology
      Information non-redundant protein database by translated Basic Local Alignment
      Search Tool (BlastX) with a cut-off E-value of 10(-5). Among the unigenes, 57,627
      were classified in the Gene Ontology database, 15,910 were assigned to Clusters
      of Orthologous Groups, and 38,565 were found in Kyoto Encyclopedia of Genes and
      Genomes. In addition, 5723 simple sequence repeats (SSRs) were discovered based
      on the unigene sequences. The transcriptome sequences and SSRs obtained represent
      a major molecular resource for P. utilis, which will extend our knowledge of the
      comparative and functional genomics of this organism and enable population
      genomic and gene-based association studies of the gall fly. 

PMID- 24682985
TI  - NOD2/CARD15 variants in Malaysian patients with sporadic colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common types of cancer in both
      developed and developing countries. This disease is triggered by and progresses
      via the sequential accumulation of multiple genetic alterations. In addition, the
      interaction between low-penetrance genes and environmental factors can also
      increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are
      one of the predisposing factors for CRC, IBD-related genes might, to a certain
      extent, be associated with cancer initiation. The nucleotide oligomerization
      domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most
      well-established gene to be associated with increased susceptibility to Crohn's
      disease. Thus, various studies have been performed to investigate the potential
      contribution of this gene to CRC risk. In this study, we aimed to determine the
      frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of
      NOD2/CARD15, and to investigate their association with CRC susceptibility. A
      total of 130 CRC patients and 212 healthy controls were recruited for this study.
      Subsequently, real-time polymerase chain reaction with TaqMan was performed for
      the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants
      was statistically associated to CRC susceptibility in our Malaysian population.
      Our findings were remarkably similar to those of other Asian cohorts, which
      indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between
      Caucasian and Asian populations. 

PMID- 24682984
TI  - Inhibition effect of silver nanoparticles on herpes simplex virus 2.
AB  - The herpes simplex virus 2 (HSV-2) is one of the most important sexually
      transmitted pathogens, and can facilitate the spread of human immunodeficiency
      virus. The currently available antiviral drugs have certain limitations.
      Nanosilver has received increasing attention recently with respect to its
      antibacterial and antiviral properties. The purpose of this study was to
      determine the inhibiting effect and mechanism of silver nanoparticles (Ag-NPs) on
      HSV-2. The cytotoxicity of Vero cells induced by different Ag-NP concentrations
      was investigated by using the methyl thiazolyl tetrazolium (MTT) assay. The
      inhibiting effect of Ag-NPs on HSV-2 at various times was also evaluated by using
      a plaque assay. The toxicity of 100 MUg/mL Ag-NPs on Vero cells was very low. The
      mixture of Ag-NP suspension and HSV-2 prior to infecting cells could
      significantly inhibit the production of progeny viruses. Ag-NPs also inhibited
      the replication of HSV-2 for 24 h before infecting cells with HSV-2. Therefore,
      100 MUg/mL Ag-NPs could completely inhibit HSV-2 replication. Ag-NPs at nontoxic
      concentrations were capable of inhibiting HSV-2 replication when administered
      prior to viral infection or soon after initial virus exposure. This suggests that
      the mode of action of Ag-Nps occurs during the early phases of viral replication.

PMID- 24682986
TI  - A randomized trial to compare pain control using oral analgesia with epidural
      analgesia after cesarean section following combined spinal-epidural anesthesia.
AB  - This study aimed to evaluate whether combined oral oxycodone hydrochloride
      controlled release tablets plus paracetamol and tramadol hydrochloride tablets
      are more effective than epidural analgesia for postoperative pain control and
      side effects after cesarean section. We randomly enrolled 60 patients scheduled
      for cesarean section into either: patient-controlled epidural analgesia with 0.1%
      ropivacaine+0.1 MUg/mL sufentanil (for postoperative 48 h)+injected pethidine on
      demand (E group); or controlled-release oxycodone (2x15 mg for the first
      postoperative 24 h; 2x10 mg for the second postoperative 24 h)+paracetamol and
      tramadol hydrochloride tablets (8x1 tablet for the postoperative 48 h)
      orally+injected pethidine on demand (O group). The E group experienced more
      evoked pain and uterine cramping pain at all times postoperatively. The patients
      who received oral analgesia had less resting pain at 6, 12, 24, and 36 h after
      surgery. Two patients in the E group injected pethidine (150 mg total) during the
      oxytocin infusion, whereas none of the O group patients injected pethidine.
      Pruritus was more common in the E group (P<0.05). Maternal satisfaction with the
      analgesia regimen was lower in the E group (P<0.01). The median duration of
      hospital stay was about 5 days for both groups. Postoperative pain control after
      cesarean section with oral oxycodone hydrochloride-controlled release tablets
      plus paracetamol and tramadol hydrochloride tablets is preferable to epidural
      analgesia, even when side effects and maternal satisfaction are taken into
      account.

PMID- 24682987
TI  - Rollover-assisted C(sp2)-C(sp3) bond formation.
AB  - Rollover cyclometalation involves bidentate heterocyclic donors, unusually acting
      as cyclometalated ligands. The resulting products, possessing a free donor atom,
      react differently from the classical cyclometalated complexes. Taking advantage
      of a "rollover"/"retro-rollover" reaction sequence, a succession of oxidative
      addition and reductive elimination in a series of platinum(II) complexes
      [Pt(N,C)(Me)(PR3)] resulted in a rare C(sp(2))-C(sp(3)) bond formation to give
      the bidentate nitrogen ligands 3-methyl-2,2'-bipyridine, 3,6-dimethyl-2,2'
      bipyridine, and 3-methyl-2-(2'-pyridyl)-quinoline, which were isolated and
      characterized. The nature of the phosphane PR3 is essential to the outcome of the
      reaction. This route constitutes a new method for the activation and
      functionalization of C-H bond in the C(3) position of bidentate heterocyclic
      compounds, a position usually difficult to functionalize.

PMID- 24682988
TI  - Periprosthetic fractures around the knee: current concepts and advances in
      management.
AB  - Knee replacement is an effective treatment for pain and functional impairment
      secondary to degenerative joint conditions. The number of knee replacements
      performed continues to rise. Periprosthetic fractures around total knee
      arthroplasties are a relatively rare complication but are complex injuries that
      require the treating surgeon to be familiar with and proficient at arthroplasty
      and trauma reconstructive techniques. An increase in life expectancy and in the
      functional demands of elderly patients may lead to an increased incidence of
      periprosthetic fractures. Supracondylar fractures of the femur are the most
      common type and this review will focus on the incidence, risk factors,
      classification, investigation, and treatment options for periprosthetic fractures
      around total knee arthroplasties. 

PMID- 24682991
TI  - Isolation of Paenibacillus pinesoli sp. nov. from forest soil in Gyeonggi-Do,
      Korea.
AB  - Using a new culture method for unculturable soil bacteria, strain NB5(T) was
      isolated from forest soil at Kyonggi University, and characterized taxonomically
      on the basis of 16S rRNA gene sequence as well as phenotypic and chemotaxonomic
      characteristics. The novel strain was a Gram- and catalase-positive, rod-shaped
      bacterium, which grew in the pH range 6.0-9.5 (optimum, 6.5-9.5) and at
      temperatures between 15 degrees C and 45 degrees C (optimum, 25-40 degrees C).
      Growth was possible at 0-5% NaCl (optimum, 0% to 3%) in nutrient, Luria-Bertani,
      and trypticase soy broths (TSB), as well as R2A medium (with optimal growth in
      TSB). A phylogenetic analysis of the 16S rRNA gene sequence showed that the novel
      strain was affiliated with the genus Paenibacillus and had 96.8% and 96.5%
      similarity to P. nanensis MX2-3(T) and P. agaridevorans DSM 1355(T),
      respectively. The predominant menaquinone in NB5(T) was MK-7; the major fatty
      acids were anteiso-C15:0 and iso-C16:0; and the DNA G+C content was 54.5 mol%. We
      propose this strain as a novel species of the genus Paenibacillus, and suggest
      the name Paenibacillus pinesoli sp. nov. (type strain, KACC 17472(T)=KEMB 9005
      025(T)=JCM 19203(T)). 

PMID- 24682992
TI  - Functional characterization of extracellular chitinase encoded by the YlCTS1 gene
      in a dimorphic yeast Yarrowia lipolytica.
AB  - The hemiascomycetes yeast Yarrowia lipolytica is a dimorphic yeast with
      alternating yeast and mycelia forms. Bioinformatic analysis revealed the presence
      of three putative chitinase genes, YlCTS1, YlCTS2, and YlCTS3, in the Y.
      lipolytica genome. Here, we demonstrated that the protein of YlCTS1 (YlCts1p),
      which contains an N-terminal secretion signal peptide, a long C-terminal Ser/Thr
      rich domain, and a chitin-binding domain, is a homologue to Saccharomyces
      cerevisiae chitinase 1 (ScCts1p). Deletion of YlCTS1 remarkably reduced
      extracellular endochitinase activity in the culture supernatant of Y. lipolytica
      and enhanced cell aggregation, suggesting a role of YlCts1p in cell separation as
      ScCts1p does in S. cerevisiae. However, loss of YlCts1p function did not affect
      hyphal formation induced by fetal bovine serum addition. The mass of YlCts1p was
      dramatically decreased by jack bean alpha-mannosidase digestion but not by PNGase
      F treatment, indicating that YlCts1p is modified only by O-mannosylation without
      N-glycosylation. Moreover, the O-glycan profile of YlCts1p was identical to that
      of total cell wall mannoproteins, supporting the notion that YlCts1p can be used
      as a good model for studying O-glycosylation in this dimorphic yeast. 

PMID- 24682990
TI  - Nontraditional therapies to treat Helicobacter pylori infection.
AB  - The Gram-negative pathogen Helicobacter pylori is increasingly more resistant to
      the three major antibiotics (metronidazole, clarithromycin and amoxicillin) that
      are most commonly used to treat infection. As a result, there is an increased
      rate of treatment failure; this translates into an overall higher cost of
      treatment due to the need for increased length of treatment and/or the
      requirement for combination or sequential therapy. Given the rise in antibiotic
      resistance, the complicated treatment regime, and issues related to patient
      compliance that stem from the duration and complexity of treatment, there is
      clearly a pressing need for the development of novel therapeutic strategies to
      combat H. pylori infection. As such, researchers are actively investigating the
      utility of antimicrobial peptides, small molecule inhibitors and naturopathic
      therapies. Herein we review and discuss each of these novel approaches as a means
      to target this important gastric pathogen. 

PMID- 24682993
TI  - Hrq1 facilitates nucleotide excision repair of DNA damage induced by 4
      nitroquinoline-1-oxide and cisplatin in Saccharomyces cerevisiae.
AB  - Hrq1 helicase is a novel member of the RecQ family. Among the five human RecQ
      helicases, Hrq1 is most homologous to RECQL4 and is conserved in fungal genomes.
      Recent genetic and biochemical studies have shown that it is a functional gene,
      involved in the maintenance of genome stability. To better define the roles of
      Hrq1 in yeast cells, we investigated genetic interactions between HRQ1 and
      several DNA repair genes. Based on DNA damage sensitivities induced by 4
      nitroquinoline-1-oxide (4-NQO) or cisplatin, RAD4 was found to be epistatic to
      HRQ1. On the other hand, mutant strains defective in either homologous
      recombination (HR) or post-replication repair (PRR) became more sensitive by
      additional deletion of HRQ1, indicating that HRQ1 functions in the RAD4-dependent
      nucleotide excision repair (NER) pathway independent of HR or PRR. In support of
      this, yeast two-hybrid analysis showed that Hrq1 interacted with Rad4, which was
      enhanced by DNA damage. Overexpression of Hrq1K318A helicase-deficient protein
      rendered mutant cells more sensitive to 4-NQO and cisplatin, suggesting that
      helicase activity is required for the proper function of Hrq1 in NER. 

PMID- 24682994
TI  - Serotype-independent protection against pneumococcal infections elicited by
      intranasal immunization with ethanol-killed pneumococcal strain, SPY1.
AB  - The 23-valent polysaccharide vaccine and the 7-valent pneumococcal conjugate
      vaccine are licensed vaccines that protect against pneumococcal infections
      worldwide. However, the incidence of pneumococcal diseases remains high in low
      income countries. Whole-cell vaccines with high safety and strong immunogenicity
      may be a favorable choice. We previously obtained a capsule-deficient
      Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an
      attenuated live pneumococcal vaccine, intranasal immunization with SPY1 elicits
      broad serotype-independent protection against pneumococcal infection. In this
      study, for safety consideration, we inactivated SPY1 with 70% ethanol and
      intranasally immunized BALB/c mice with killed SPY1 plus cholera toxin adjuvant
      for four times. Results showed that intranasal immunization with inactivated SPY1
      induced strong humoral and cellular immune responses. Intranasal immunization
      with inactivated SPY1 plus cholera toxin adjuvant elicited effective serotype
      independent protection against the colonization of pneumococcal strains 19F and 4
      as well as lethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The
      protection rates provided by inactivated SPY1 against lethal pneumococcal
      infection were comparable to those of currently used polysaccharide vaccines. In
      addition, vaccine-specific B-cell and T-cell immune responses mediated the
      protection elicited by SPY1. In conclusion, the 70% ethanol-inactivated
      pneumococcal whole-cell vaccine SPY1 is a potentially safe and less complex
      vaccine strategy that offers broad protection against S. pneumoniae. 

PMID- 24682995
TI  - RNA interference targeting nucleocapsid protein inhibits porcine reproductive and
      respiratory syndrome virus replication in Marc-145 cells.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an important disease,
      which leads to severe economic losses in swine-producing areas of the world.
      However, current antiviral strategies cannot provide highly effective protection.
      In this study, three theoretically effective interference target sites (71-91,
      144-164, 218-238) targeting the nucleocapsid (N) gene of PRRSV were designed and
      selected, and then three siRNA-expressing plasmids were constructed, respectively
      named p2.1-N71, p2.1-N144, and p2.1-N218. The recombinant siRNA-expressing
      plasmids were transfected into Marc-145 cells; then the cells were infected with
      PRRSV (JL07SW strain); finally, after incubation for 48 h, the antiviral activity
      of those siRNA-expressing plasmids in Marc-145 cells was assessed by cytopathic
      effects, virus titers, indirect immunofluorescence, and quantitative real-time
      PCR. Experimental results demonstrated that these three siRNA-expressing plasmids
      could effectively and significantly inhibit the replication of PRRSV by 93.2%,
      83.6%, and 89.2% in Marc-145 cells, respectively. Among these three siRNA
      expressing plasmids, p2.1-N71 was found to be most effective, while p2.1-N144 and
      p2.1-N218 displayed relatively weak inhibition of virus replication. The results
      indicated that siRNA-expressing plasmids targeting the N gene of PRRSV could
      significantly inhibit PRRSV replication in Marc-145 cells. Based on our
      experimental results and previous reports, the 71-91, 179-197, and 234-252 sites
      of the N gene are good choices to effectively inhibit the replication of PRRSV,
      and this RNA interference technique can be a potential anti-PRRSV strategy. 

PMID- 24682996
TI  - Antiviral effect of flavonol glycosides isolated from the leaf of Zanthoxylum
      piperitum on influenza virus.
AB  - The ethanol extract of Zanthoxylum piperitum (L.) DC. showed in vitro antiviral
      activity against influenza A virus. Three flavonol glycosides were isolated from
      the EtOAc fraction of Z. piperitum leaf by means of activity-guided
      chromatographic separation. Structures of isolated compounds were identified as
      quercetin 3-O-beta-D-galactopyranoside (1), quercetin 3-O-alpha-L
      rhamnopyranoside (2), kaempferol 3-O-alpha-L-rhamnopyranoside (3) by comparing
      their spectral data with literature values. The anti-influenza viral activity of
      isolates was evaluated using a plaque reduction assay against influenza A/NWS/33
      (H1N1) virus. The compounds also were subjected to neuraminidase inhibition assay
      in influenza A/NWS/33 virus. Compounds 1-3 exhibited antiviral activity against
      an influenza A virus in vitro, and inhibited the neuraminidase activity at
      relatively high concentrations. 

PMID- 24682999
TI  - Redox non-innocence of coordinated 2-(arylazo) pyridines in iridium complexes:
      characterization of redox series and an insight into voltage-induced current
      characteristics.
AB  - Two examples of a rare class of di-radical azo-anion complexes of 2-(arylazo)
      pyridine with Ir(III) carrier are introduced. Their electronic structures have
      been elucidated using a host of physical methods that include X-ray
      crystallography, cyclic voltammetry, electron paramagnetic resonance
      spectroscopy, and density functional theory. Room temperature magnetic moments of
      these are consistent with two nearly non-interacting azo-anion radicals. These
      displayed rich electrochemical properties consisting of six numbers of reversible
      and successive one electron CV-waves. Redox processes occur entirely at the
      coordinated ligands without affecting metal redox state. Apart from reporting
      their chemical characterization, I-V characteristics of these complexes in film
      state are investigated using sandwich-type devices comprising of a thin film of
      100-125 nm thickness placed between two gold-plated ITO electrodes. These showed
      memory switching properties covering a useful voltage range with a reasonable
      ON/OFF ratio and also are suitable for RAM/ROM applications. I-V characteristics
      of two similar complexes of Rh and Cr with identical ligand environment and
      electronic structure are also referred for developing an insight into the memory
      switching ability of Ir- and Rh- complexes on the basis of comparative analysis
      of responses of the respective systems. In a nutshell, thorough analysis of
      voltage driven redox dynamics and corresponding solid and solution state current
      responses of all the systems are attempted and there from an unexplored class of
      switching devices are systematically introduced. 

PMID- 24682997
TI  - Development of a chimeric strain of porcine reproductive and respiratory syndrome
      virus with an infectious clone and a Korean dominant field strain.
AB  - The K418 chimeric virus of porcine reproductive and respiratory syndrome virus
      (PRRSV) was engineered by replacing the genomic region containing structure
      protein genes of an infectious clone of PRRSV, FL12, with the same region
      obtained from a Korean dominant field strain, LMY. The K418 reached 10(6)
      TCID50/ml of viral titer with similar growth kinetics to those of parental
      strains and had a cross-reactive neutralizing antibody response to field serum
      from the entire country. The chimeric clone pK418 can be used as a practical tool
      for further studying the molecular characteristics of PRRSV proteins through
      genetic manipulation. Furthermore, successful construction of the K418 will allow
      for the development of customized vaccine candidates against PRRSV, which has
      evolved rapidly in Korea. 

PMID- 24683000
TI  - Synthesis and cytotoxic activity of 2-anilinopyridine-3-acrylamides as tubulin
      polymerization inhibitors.
AB  - In an attempt to develop potent anticancer agents, a series of 2-anilinonicotinyl
      linked acrylamide conjugates were designed, synthesized, and evaluated for
      cytotoxic activity against various human cancer cell lines, anti-tubulin activity
      and cell-cycle effects. Among the series, compounds 6 d [(E)-N-(6
      fluorobenzo[d]thiazol-2-yl)-3-(2-((3,4,5-trimethoxyphenyl)amino)pyridin-3
      yl)acrylamide] and 6 p [(E)-3-(2-((4-methoxyphenyl)amino)pyridin-3-yl)-N-(6
      nitrobenzo[d]thiazol-2-yl)acrylamide] showed promising cytotoxicity, specifically
      against the A549 human lung adenocarcinoma epithelial cell line, with GI50 values
      of 0.6+/-0.23 and 1.8+/-0.22 MUM, respectively. Furthermore, cell-cycle
      perturbation studies by flow cytometry analysis indicated drastic cell-cycle
      effects in the G2 /M phase in this cell line followed by caspase-3 activation and
      apoptotic cell death. Molecular docking studies of the most potent compound, 6 d,
      revealed that this compound interacts with and binds efficiently in the active
      site of tubulin. 

PMID- 24683001
TI  - Mantle cell lymphoma harboring Burkitt's-like translocations presents
      differential expression of aurora kinase genes compared with others 8q
      abnormalities.
AB  - We compared the levels of AURKA and AURKB in 24 (mantle cell lymphoma) MCL
      patients harboring 8q abnormalities and its relationship with MYCC gene status.
      Two distinct subgroups were observed, in terms of MYCC expression. Except for the
      patients with Burkitt's-like translocation, none of the patients harboring 8q
      abnormalities, including balanced translocations or duplications of MYCC band,
      identified both by G-banding and SKY, showed differential expression levels of
      MYCC. These previous findings also reflected in the differential expression of
      AURKA and AURKB genes. We found that AURKA and AURKB mRNA were expressed at
      significantly higher levels in MCL patients harboring Burkitt's-like
      translocation, when compared to patients with 8q rearrangements. The high
      expression of aurora kinase genes is reported to be associated with some
      parameters of clinical oncologic aggressiveness, such as high histological grade,
      invasion and increased rates of metastasis in several types of cancers. It is
      possible that in MCL patients expressing abnormal levels of MYCC together with a
      high expression of AURKA might offer some resistant to the conventional therapy
      purposes. Thus, aurora kinase inhibitors may also be considered for this specific
      subgroup on MCL, whose aggressive clinical course resembles high-grade lymphoma. 

PMID- 24683002
TI  - Anticoagulation versus placebo for heart failure in sinus rhythm.
AB  - BACKGROUND: Patients with chronic heart failure (heart failure) are at risk of
      thromboembolic events, including stroke, pulmonary embolism and peripheral
      arterial embolism, whilst coronary ischaemic events also contribute to the
      progression of heart failure. Long-term oral anticoagulation is established in
      certain patient groups, including patients with heart failure and atrial
      fibrillation, but there is wide variation in the indications and use of oral
      anticoagulation in the broader heart failure population. OBJECTIVES: To determine
      whether long-term oral anticoagulation reduces total deaths, cardiovascular
      deaths and major thromboembolic events in patients with heart failure. SEARCH
      METHODS: We updated the searches in June 2030 in the electronic databases CENTRAL
      (Issue 6, 2013) in The Cochrane Library, MEDLINE (OVID, 1946 to June week 1 2013)
      and EMBASE (OVID, 1980 to 2013 week 23). Reference lists of papers and abstracts
      from national and international cardiovascular meetings were studied to identify
      unpublished studies. Relevant authors were contacted to obtain further data. No
      language restrictions were applied. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing oral anticoagulants with placebo in adults with heart
      failure, and with treatment duration at least one month. Non-randomised studies
      were also included for assessing side effects. Inclusion decisions were made in
      duplicate and any disagreement between review authors was resolved by discussion
      or a third party. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trials for inclusion and assessed the risks and benefits of
      antithrombotic therapy using relative measures of effects, such as odds ratio,
      accompanied by the 95% confidence intervals. MAIN RESULTS: Two RCTs were
      identified. One compared warfarin, aspirin and no antithrombotic therapy and the
      second compared warfarin with placebo in patients with idiopathic dilated
      cardiomyopathy. Three small prospective controlled studies of warfarin in heart
      failure were also identified, but they were over 50 years old with methods not
      considered reliable by modern standards. In both WASH 2004 and HELAS 2006, there
      were no significant differences in the incidence of myocardial infarction, non
      fatal stroke and death between patients taking oral anticoagulation and those
      taking placebo. Four retrospective non-randomised cohort analyses and four
      observational studies of oral anticoagulation in heart failure included differing
      populations of heart failure patients and reported contradictory results.
      AUTHORS' CONCLUSIONS: Based on the two major randomised trials (HELAS 2006; WASH
      2004), there is no convincing evidence that oral anticoagulant therapy modifies
      mortality or vascular events in patients with heart failure and sinus rhythm.
      Although oral anticoagulation is indicated in certain groups of patients with
      heart failure (for example those with atrial fibrillation), the available data
      does not support the routine use of anticoagulation in heart failure patients who
      remain in sinus rhythm.

PMID- 24683003
TI  - Ion-responsive hemin-G-quadruplexes for switchable DNAzyme and enzyme functions.
AB  - Programmed nucleic acid sequences undergo K(+) ion-induced self-assembly into G
      quadruplexes and separation of the supramolecular structures by the elimination
      of K(+) ions by crown ether or cryptand ion-receptors. This process allows the
      switchable formation and dissociation of the respective G-quadruplexes. The
      different G-quadruplex structures bind hemin, and the resulting hemin-G
      quadruplex structures reveal horseradish peroxidase DNAzyme catalytic activities.
      The following K(+) ion/receptor switchable systems are described: 1) The K(+) 
      induced self-assembly of the Mg(2+) -dependent DNAzyme subunits into a catalytic
      nanostructure using the assembly of G-quadruplexes as bridging unit. 2) The K(+) 
      induced stabilization of the anti-thrombin G-quadruplex nanostructure that
      inhibits the hydrolytic functions of thrombin. 3) The K(+) -induced opening of
      DNA tweezers through the stabilization of G-quadruplexes on the "tweezers' arms"
      and the release of a strand bridging the tweezers into a closed structure. In all
      of the systems reversible, switchable, functions are demonstrated. For all
      systems two different signals are used to follow the switchable functions
      (fluorescence and the catalytic functions of the derived hemin-G-quadruplex
      DNAzyme). 

PMID- 24683006
TI  - Supramolecular organogels based on dendrons and dendrimers.
AB  - Dendrons and dendrimers have well-defined, discrete structures that can be
      precisely controlled at the molecular lever. Owing to their unique architectures
      and multiple functionalities, dendritic molecules have shown intensive self
      assembly behavior and functional performance. In particular, they have been shown
      to be promising candidates for applications in the assembly of gel-phase
      materials. Furthermore, the introduction of suitable functional moieties into the
      core, the branches, and/or the periphery of the dendritic gelators enables the
      construction of smart and functional supramolecular gel materials. Over the past
      decade, a number of dendritic organogelators that are based on poly(amino acid),
      poly(amide), and poly(aryl ether) dendrons, or together with multiple alkyl
      chains on the periphery, have been reported. This review describes the important
      developments in dendritic organogelators, with an emphasis on new strategies for
      the molecular design of dendritic gelators, understanding of driving forces for
      gel formation, and their evolution for potential applications in smart soft
      materials. 

PMID- 24683009
TI  - Amnioinfusion for third trimester preterm premature rupture of membranes.
AB  - BACKGROUND: Preterm premature rupture of membranes (PPROM) is a leading cause of
      perinatal morbidity and mortality. Amnioinfusion aims to restore amniotic fluid
      volume by infusing a solution into the uterine cavity. OBJECTIVES: The objective
      of this review was to assess the effects of amnioinfusion for PPROM on perinatal
      and maternal morbidity and mortality. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (2 December 2013). SELECTION
      CRITERIA: Randomised trials of amnioinfusion compared with no amnioinfusion in
      women with PPROM. DATA COLLECTION AND ANALYSIS: Three review authors
      independently assessed trials for inclusion. Two review authors independently
      assessed trial quality and extracted data. Data were checked for accuracy. MAIN
      RESULTS: We included five trials, of moderate quality, but we only analysed data
      from four studies (with a total of 241 participants). One trial did not
      contribute any data to the review.Transcervical amnioinfusion improved fetal
      umbilical artery pH at delivery (mean difference 0.11; 95% confidence interval
      (CI) 0.08 to 0.14; one trial, 61 participants) and reduced persistent variable
      decelerations during labour (risk ratio (RR) 0.52; 95% CI 0.30 to 0.91; one
      trial, 86 participants).Transabdominal amnioinfusion was associated with a
      reduction in neonatal death (RR 0.30; 95% CI 0.14 to 0.66; two trials, 94
      participants), neonatal sepsis (RR 0.26; 95% CI 0.11 to 0.61; one trial, 60
      participants), pulmonary hypoplasia (RR 0.22; 95% CI 0.06 to 0.88; one trial, 34
      participants) and puerperal sepsis (RR 0.20; 95% CI 0.05 to 0.84; one trial, 60
      participants). Women in the amnioinfusion group were also less likely to deliver
      within seven days of membrane rupture (RR 0.18; 95% CI 0.05 to 0.70; one trial,
      34 participants). These results should be treated with circumspection as the
      positive findings were mainly due to one trial with unclear allocation
      concealment. AUTHORS' CONCLUSIONS: These results are encouraging but are limited
      by the sparse data and unclear methodological robustness, therefore further
      evidence is required before amnioinfusion for PPROM can be recommended for
      routine clinical practice.

PMID- 24683007
TI  - Biweekly cetuximab plus FOLFIRI/irinotecan as first/second-line chemotherapy for
      patients with KRAS wild-type metastatic colorectal cancer: a retrospective
      analysis in Southwest Chinese population.
AB  - Weekly cetuximab plus irinotecan-based regiments are standard first- and second
      line chemotherapy for patients with KRAS wild-type metastatic colorectal cancer
      (mCRC). However, the chemotherapy regimens are given every 2 weeks, which is
      asynchronous with cetuximab weekly administration. This study investigated the
      efficacy and safety of biweekly cetuximab administration in patients with mCRC.
      Twenty-six patients with KRAS wild-type mCRC, who received biweekly cetuximab
      plus FOLFIRI/irinotecan as first/second-line chemotherapy, at least three cycles
      of cetuximab and once CT evaluation in West China Hospital from May 2010 to
      February 2013, were retrospectively analyzed. The median number of cetuximab
      administrations was 8.3 (range 3-20). Fourteen patients received FOLFIRI as first
      line therapy; response rate was 50.0%; median PFS was 8.8 months (95% CI 4.9
      12.7). Ten patients received FOLFIRI and two patients received irinotecan as
      second-line therapy; response rate was 33.3%; median PFS was 4.6 months (95% CI
      0.9-8.3). The toxicity was similar to weekly cetuximab combination schedules.
      Rash was observed in 69.2% of evaluable patients (grade 3 in 7.7%). Overall, our
      results show that biweekly cetuximab plus FOLFIRI/irinotecan may be as effective
      and safe as the standard weekly schedule.

PMID- 24683010
TI  - Particulate air pollution and preeclampsia: a source-based analysis.
AB  - OBJECTIVES: To investigate the association between preeclampsia and maternal
      exposure to ambient particulate matter (PM) with aerodynamic diameter less than
      10 MUm (PM10) and 2.5 MUm (PM2.5) mass and sources. METHODS: Our analysis was
      based on a hospital cohort of pregnant women (N=3182) residing in Barcelona,
      Spain, during 2003-2005. Positive matrix factorisation source apportionment
      (PMF2) was used to identify sources of PM10 and PM2.5 samples obtained by an
      urban background monitor, resulting in detection of eight sources. We further
      combined traffic-related sources (brake dust, vehicle exhaust and secondary
      nitrate/organics) to generate an indicator of combined traffic sources. Logistic
      regression models were developed to estimate the association between preeclampsia
      and exposure to each PM source and mass separately during the entire pregnancy
      and trimester one, adjusted for relevant covariates. RESULTS: For the exposure
      during the entire pregnancy, we found a 44% (95% CI 7% to 94%) and a 80% (95% CI
      4% to 211%) increase in the risk of preeclampsia associated with one IQR increase
      in exposure to PM10 brake dust and combined traffic-related sources,
      respectively. These findings remained consistent after an alternative source
      apportionment method (Multilinear Engine (ME2)) was used. The results for PM2.5
      mass and sources and also exposure during trimester one were inconclusive.
      CONCLUSIONS: Risk of preeclampsia was associated with exposure to PM10 brake dust
      and combined traffic-related sources.

PMID- 24683004
TI  - Prevalence of dental pain and its relationship to caries experience in school
      children of Udupi district.
AB  - PURPOSE: To evaluate the prevalence of dental pain and its relationship to caries
      experience in 10-15-year-old school children of Udupi district of India. METHODS:
      A cross-sectional survey was conducted in Udupi district among 10-15-year-old
      school children. A self-administered questionnaire was used to collect
      information on age, gender, type of school, location and socioeconomic status
      followed by Child Dental Pain Questionnaire. This was followed by clinical
      examination for dental caries. RESULTS: A total of 306 children participated in
      the study; of whom, 56.5% were <=12 years old, 58.8% were males, 50.7% attended a
      government school and 54.9% were from urban areas. The prevalence of dental pain
      was 35%. Only gender showed significant association with presence of tooth pain
      (p = 0.027). A total of 14.3% reported mild pain, 8.8% reported moderate pain and
      11.7% reported severe pain. Almost half of the study participants (45.1%) had
      experienced dental caries. The mean scores of each subscale and total scale
      scores were significantly higher among caries-experienced than among caries-free
      children (p = 0.017, 0.043, 0.022 and 0.02, respectively). There was significant
      weak positive correlation of global single item question with prevalence (r =
      0.115, p = 0.045), severity (r = 0.146, p = 0.010) impact subscales (r = 0.117, p
      = 0.040) and total scale (r = 0.144, p = 0.012). CONCLUSION: The substantial
      effect that dental pain has on adolescents indicates an urgent need for public
      health strategies.

PMID- 24683005
TI  - Smooth muscle cells and the formation, degeneration, and rupture of saccular
      intracranial aneurysm wall--a review of current pathophysiological knowledge.
AB  - Subarachnoid hemorrhage or intracerebral hemorrhage caused by rupture of a
      saccular intracranial aneurysm (sIA) is often fatal and causes significant loss
      of productive live years in addition to significant mortality. Around 3.5 % of
      the middle aged otherwise healthy population carries unruptured sIAs. Many sIAs
      never rupture, and since their prophylactic treatment is associated with risks of
      morbidity and even mortality, it is paramount to elucidate the biology that leads
      to sIA rupture in order be able to identify rupture-prone sIAs and to improve
      current therapies. Smooth muscle cells (SMCs) play a critical role both in the
      formation of sIAs, as well as in the repair and adaptation of the sIA wall to
      hemodynamic and proteolytic stress to which it is subjected. Loss of mural SMCs
      is characteristic to ruptured sIA walls, and experiments in animal models suggest
      that this loss of mural SMCs is causative to sIA growth and eventual rupture.
      Genetic factors that impair the function or survival of SMCs may predispose to
      sIA formation. Local or systemic therapy that increases the number of functioning
      SMCs in the sIA wall may have a potential to reduce the risk of sIA rupture. This
      review discusses the mechanisms and cellular interactions that SMCs have in the
      pathobiology of the sIA wall. 

PMID- 24683008
TI  - Expression of cytoskeleton regulatory protein Mena in human hepatocellular
      carcinoma and its prognostic significance.
AB  - The molecular mechanisms of the development and progression of hepatocellular
      carcinoma (HCC) are poorly understood. The main objective of this study was to
      analyze the expression of Enabled [mammalian Ena (Mena)] protein and its clinical
      significance in human HCC. The Mena expression was examined at mRNA and protein
      levels by real-time quantitative polymerase chain reaction and Western blotting
      analysis in ten paired HCC tissues and the adjacent normal tissues. The
      expression of Mena protein in 81 specimens of HCC tissues was determined by
      immunohistochemistry. Associations of Mena expression with the
      clinicopathological features were analyzed, and prognosis of HCC patients was
      evaluated. The result shows the expression of Mena mRNA and protein was higher in
      HCC than in the adjacent normal tissues in ten paired samples. Mena was mainly
      accumulated in the cytoplasm of tumor cells and over-expressed in 40.74% (33/81)
      patients by immunohistochemical staining. Over-expression of Mena was
      significantly associated with poor cellular differentiation (P = 0.025), advanced
      tumor stage (P = 0.003) and worse disease-free survival (DFS, P < 0.001). In
      addition, Mena is an independent prognostic factor for DFS in multivariate
      analysis (HR 2.309, 95% CI 1.104-4.828; P = 0.026). Mena is up-regulated in HCC
      and associated with tumor differentiation and clinical stage. Mena may be an
      independent prognostic marker for DFS of HCC patients.

PMID- 24683011
TI  - Exhaled nitric oxide in spray painters exposed to isocyanates: effect
      modification by atopy and smoking.
AB  - BACKGROUND: Isocyanate asthma is one of the most frequently identified forms of
      occupational asthma in industrialised countries. The underlying mechanisms have
      not been clarified. There is only limited information about the relationship
      between exhaled nitric oxide (eNO) and occupational exposure to isocyanates and
      asthma. OBJECTIVES: To investigate the association between isocyanate exposure
      and eNO levels in isocyanate-exposed workers and to elucidate whether eNO acts as
      a marker of airway inflammation controlling for smoking and atopy in an industry
      wide survey. METHODS: Information on estimated personal isocyanate exposure,
      measured eNO levels, health effects and sensitisation were analysed in 229
      workers from a cross-sectional study. Univariate and multiple regression analyses
      were used to explore the exposure-response relationships between isocyanate
      exposure and eNO, stratified by smoking and atopy. RESULTS: A marginally
      significant exposure-response relationship was found between isocyanate exposure
      and eNO in atopic, non-smokers (p=0.054). eNO was significantly associated with
      atopy and smoking, bronchial hyper-responsiveness (BHR), work-related
      conjunctivitis and rhinitis after adjustment for age, gender, atopy and smoking
      (p<0.05). A borderline significant association was found between eNO and asthma
      like symptoms after adjustment for age, gender, atopy and current smoking
      (p=0.055). In a small group of isocyanate-exposed workers with positive serum
      specific immunoglobulin E (IgE) antibodies to hexamethylene diisocyanate (HDI),
      elevated eNO levels were clearly exposure related. eNO was associated with the
      positive specific IgG antibodies to HDI in non-atopic, non-smokers (p=0.03).
      CONCLUSIONS: Increased eNO levels may indicate increased airway inflammation in
      atopic, non-smokers exposed to isocyanates especially at higher levels of
      isocyanate exposure.

PMID- 24683013
TI  - Is there a lung cancer risk in US coal miners?

PMID- 24683015
TI  - High-mass MALDI-MS using ion conversion dynode detectors: influence of the
      conversion voltage on sensitivity and spectral quality.
AB  - With the development of special ion conversion dynode (ICD) detectors for high
      mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS),
      the mass-to-charge ratio is no longer a limiting factor. Although these detectors
      have been successfully used in the past, there is lack of understanding of the
      basic processes in the detector. We present a systematic study to investigate the
      performance of such an ICD detector and separate the contributions of the MALDI
      process from the ones of the ion-to-secondary ion and the secondary ion-to
      electron conversions. The performance was evaluated as a function of the voltages
      applied to the conversion dynodes and the sample amount utilized, and we found
      that the detector reflects the MALDI process correctly: limitations such as
      sensitivity or deviations from the expected signal intensity ratios originate
      from the MALDI process itself and not from the detector. 

PMID- 24683012
TI  - Identifying gender differences in reported occupational information from three US
      population-based case-control studies.
AB  - OBJECTIVES: Growing evidence suggests that gender-blind assessment of exposure
      may introduce exposure misclassification, but few studies have characterised
      gender differences across occupations and industries. We pooled control responses
      to job-specific, industry-specific and exposure-specific questionnaires (modules)
      that asked detailed questions about work activities from three US population
      based case-control studies to examine gender differences in work tasks and their
      frequencies. METHODS: We calculated the ratio of female-to-male controls that
      completed each module. For four job modules (assembly worker, machinist, health
      professional, janitor/cleaner) and for subgroups of jobs that completed those
      modules, we evaluated gender differences in task prevalence and frequency using
      chi(2) and Mann-Whitney U tests, respectively. RESULTS: The 1360 female and 2245
      male controls reported 6033 and 12 083 jobs, respectively. Gender differences in
      female:male module completion ratios were observed for 39 of 45 modules completed
      by >=20 controls. Gender differences in task prevalence varied in direction and
      magnitude. For example, female janitors were significantly more likely to polish
      furniture (79% vs 44%), while male janitors were more likely to strip floors (73%
      vs 50%). Women usually reported more time spent on tasks than men. For example,
      the median hours per week spent degreasing for production workers in product
      manufacturing industries was 6.3 for women and 3.0 for men. CONCLUSIONS: Observed
      gender differences may reflect actual differences in tasks performed or
      differences in recall, reporting or perception, all of which contribute to
      exposure misclassification and impact relative risk estimates. Our findings
      reinforce the need to capture subject-specific information on work tasks.

PMID- 24683016
TI  - [Prevalence of metabolic complications after 10 years of antiretroviral treatment
      in Senegal].
AB  - Among the patients of the cohort still followed after a median of 9 years of
      antiretroviral treatment (ART), 37% had lipodystrophy, 28% had hypertension and
      14% presented with diabetes. This study confirms the association between
      stavudine and lipodystrophy particulary lipoatrophy and shows that a longer
      duration of ART was associated with the presence of diabetes. These results
      highlight the need to implement programs for prevention of cardiovascular risk
      factors in HIV patients from resource-constrained settings. 

PMID- 24683014
TI  - Radiological imaging in ataxia telangiectasia: a review.
AB  - The human genetic disorder ataxia telangiectasia (A-T) is characterised by
      neurodegeneration, immunodeficiency, radiosensitivity, cell cycle checkpoint
      defects, genomic instability and cancer predisposition. Progressive cerebellar
      ataxia represents the most debilitating aspect of this disorder. At present,
      there is no therapy available to cure or prevent the progressive symptoms of A-T.
      While it is possible to alleviate some of the symptoms associated with
      immunodeficiency and deficient lung function, neither the predisposition to
      cancer nor the progressive neurodegeneration can be prevented. Significant effort
      has focused on improving our understanding of various clinical, genetic and
      immunological aspects of A-T; however, little attention has been directed towards
      identifying altered brain structure and function using MRI. To date, most imaging
      studies have reported radiological anomalies in A-T. This review outlines the
      clinical and biological features of A-T along with known radiological imaging
      anomalies. In addition, we briefly discuss the advent of high-resolution MRI in
      conjunction with diffusion-weighted imaging, which enables improved investigation
      of the microstructural tissue environment, giving insight into the loss in
      integrity of motor networks due to abnormal neurodevelopmental or progressive
      neurodegenerative processes. Such imaging approaches have yet to be applied in
      the study of A-T and could provide important new information regarding the
      relationship between mutation of the ataxia telangiectasia mutated (ATM) gene and
      the integrity of motor circuitry. 

PMID- 24683017
TI  - Perceptions of lipodystrophy among PLHIV after 10 years of antiretroviral therapy
      in Senegal.
AB  - Nearly one-third of people living with HIV (PLHIV) and taking HAART develop
      lipodystrophy in Africa. This article aims to describe how they perceive these
      disorders and the determinants of these perceptions. It is based on a qualitative
      study using interviews conducted with 20 patients with clinical lipodystrophy in
      Dakar, Senegal. Not all of the interviewees complained, though some had clearly
      visible lipodystrophy. The hypertrophic form seems better tolerated when
      perceived as overweight, a sign of excess wealth. Atrophic forms sometimes go
      unnoticed in lean people, but others experience it as stigma, avoid appearing in
      public, and express significant suffering, especially when symptoms jeopardize
      their social status. Healthcare systems should take better account of
      lipodystrophy and its psychosocial effects because they weaken adherence and
      reduce patients' quality of life. 

PMID- 24683018
TI  - The B(C6F5)3 boron Lewis acid route to arene-annulated pentalenes.
AB  - 4,5-Dimethyl-1,2-bis(1-naphthylethynyl)benzene (12) undergoes a rapid multiple
      ring-closure reaction upon treatment with the strong boron Lewis acid B(C6F5)3 to
      yield the multiply annulated, planar conjugated pi-system 13 (50 % yield). In the
      course of this reaction, a C6F5 group was transferred from boron to carbon.
      Treatment of 12 with CH3B(C6F5)2 proceeded similarly, giving a mixture of 13
      (C6F5-transfer) and the product 15, which was formed by CH3-group transfer. 1,2
      Bis(phenylethynyl)benzene (8 a) reacts similarly with CH3B(C6F5)2 to yield a
      mixture of the respective C6F5- and CH3-substituted dibenzopentalenes 10 a and
      16. The reaction is thought to proceed through zwitterionic intermediates that
      exhibit vinyl cation reactivities. Some B(C6F5)3-substituted species (26, 27)
      consequently formed by in situ deprotonation upon treatment of the respective 1,2
      bis(alkynyl)benzene starting materials (24, 8) with the frustrated Lewis pair
      B(C6F5)3/P(o-tolyl)3. The overall formation of the C6F5-substituted products
      formally require HB(C6F5)2 cleavage in an intermediate dehydroboration step. This
      was confirmed in the reaction of a thienylethynyl-containing starting material 21
      with B(C6F5)3, which gave the respective annulated pentalene product 23 that had
      the HB(C6F5)2 moiety 1,4-added to its thiophene ring. Compounds 12-14, 23, and 26
      were characterized by X-ray diffraction.

PMID- 24683020
TI  - Vasectomy occlusion techniques for male sterilization.
AB  - BACKGROUND: Vasectomy is an increasingly popular and effective family planning
      method. A variety of vasectomy techniques are used worldwide, including vas
      occlusion techniques (excision and ligation, thermal or electrocautery, and
      mechanical and chemical occlusion methods), as well as vasectomy with vas
      irrigation or with fascial interposition. Vasectomy guidelines largely rely on
      information from observational studies. Ideally, the choice of vasectomy
      techniques should be based on the evidence from randomized controlled trials
      (RCTs). OBJECTIVES: The objective of this review was to compare the
      effectiveness, safety, acceptability and costs of vasectomy techniques for male
      sterilization. SEARCH METHODS: In February 2014, we updated the searches of
      CENTRAL, MEDLINE, POPLINE and LILACS. We looked for recent clinical trials in
      ClinicalTrials.gov and the International Clinical Trials Registry Platform.
      Previous searches also included EMBASE. For the initial review, we searched the
      reference lists of relevant articles and book chapters. SELECTION CRITERIA: We
      included RCTs comparing vasectomy techniques, which could include suture
      ligature, surgical clips, thermal or electrocautery, chemical occlusion, vas
      plugs, vas excision, open-ended vas, fascial interposition, or vas irrigation.
      DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts located in the
      literature searches. Two reviewers independently extracted data from articles
      identified for inclusion. Outcome measures include contraceptive efficacy,
      safety, discontinuation, and acceptability. Peto odds ratios (OR) with 95%
      confidence intervals (CI) were used for dichotomous outcomes, such as
      azoospermia. The mean difference (MD) was used for the continuous variable of
      operating time. MAIN RESULTS: Six studies met the inclusion criteria. One trial
      compared vas occlusion with clips versus a conventional vasectomy technique. No
      difference was found in failure to reach azoospermia (no sperm detected). Three
      trials examined vasectomy with vas irrigation. Two studies looked at irrigation
      with water versus no irrigation, while one examined irrigation with water versus
      the spermicide euflavine. None found a difference between the groups for time to
      azoospermia. However, one trial reported that the median number of ejaculations
      to azoospermia was lower in the euflavine group compared to the water irrigation
      group. One high-quality trial compared vasectomy with fascial interposition
      versus vasectomy without fascial interposition. The fascial interposition group
      was less likely to have vasectomy failure. Fascial interposition had more
      surgical difficulties, but the groups were similar in side effects. Lastly, one
      trial found that an intra-vas was less likely to produce azoospermia than was no
      scalpel vasectomy. More men were satisfied with the intra-vas device, however.
      AUTHORS' CONCLUSIONS: For vas occlusion with clips or vasectomy with vas
      irrigation, no conclusions can be made as those studies were of low quality and
      underpowered. Fascial interposition reduced vasectomy failure. An intra-vas
      device was less effective in reducing sperm count than was no-scalpel vasectomy.
      RCTs examining other vasectomy techniques were not available. More and better
      quality research is needed to examine vasectomy techniques.

PMID- 24683021
TI  - Scalpel versus no-scalpel incision for vasectomy.
AB  - BACKGROUND: Currently, the two most common surgical techniques for approaching
      the vas during vasectomy are the incisional method and the no-scalpel technique.
      Whereas the conventional incisional technique involves the use of a scalpel to
      make one or two incisions, the no-scalpel technique uses a sharp-pointed, forceps
      like instrument to puncture the skin. The no-scalpel technique aims to reduce
      adverse events, especially bleeding, bruising, hematoma, infection and pain and
      to shorten the operating time. OBJECTIVES: The objective of this review was to
      compare the effectiveness, safety, and acceptability of the incisional versus no
      scalpel approach to the vas. SEARCH METHODS: In February 2014, we searched the
      computerized databases of CENTRAL, MEDLINE, POPLINE and LILACS. We looked for
      recent clinical trials in ClinicalTrials.gov and the International Clinical
      Trials Registry Platform. Previous searches also included in EMBASE. For the
      initial review, we searched the reference lists of relevant articles and book
      chapters. SELECTION CRITERIA: Randomized controlled trials and controlled
      clinical trials were included in this review. No language restrictions were
      placed on the reporting of the trials. DATA COLLECTION AND ANALYSIS: We assessed
      all titles and abstracts located in the literature searches and two authors
      independently extracted data from the articles identified for inclusion. Outcome
      measures included safety, acceptability, operating time, contraceptive efficacy,
      and discontinuation. We calculated Peto odds ratios (OR) with 95% confidence
      intervals (CI) for the dichotomous variables. MAIN RESULTS: Two randomized
      controlled trials evaluated the no-scalpel technique and differed in their
      findings. The larger trial demonstrated less perioperative bleeding (OR 0.49; 95%
      CI 0.27 to 0.89) and pain during surgery (OR 0.75; 95% CI 0.61 to 0.93), scrotal
      pain (OR 0.63; 95% 0.50 to 0.80), and incisional infection (OR 0.21; 95% CI 0.06
      to 0.78) during follow up than the standard incisional group. Both studies found
      less hematoma with the no-scalpel technique (OR 0.23; 95% CI 0.15 to 0.36).
      Operations using the no-scalpel approach were faster and had a quicker resumption
      of sexual activity. The smaller study did not find these differences; however,
      the study could have failed to detect differences due to a small sample size as
      well as a high loss to follow up. Neither trial found differences in vasectomy
      effectiveness between the two approaches to the vas. AUTHORS' CONCLUSIONS: The no
      scalpel approach to the vas resulted in less bleeding, hematoma, infection, and
      pain as well as a shorter operation time than the traditional incision technique.
      No difference in effectiveness was found between the two approaches.

PMID- 24683024
TI  - Presence in, and release of, nanomaterials from consumer products.
AB  - Widespread use of engineered nanomaterials (ENMs) in consumer products has led to
      concerns about their potential impact on humans and the environment. In order to
      fully assess the impacts and release of ENMs from consumer products, this chapter
      provides an overview of the types of consumer products that contain
      nanomaterials, the potential release mechanisms of these ENMs from consumer
      products, and the associated human exposure. Information from two large datasets
      on consumer goods associated with ENMs, namely, the U.S.-based Project for
      Emerging Nanotechnologies from the Woodrow Wilson International Center, and the
      European-based National Institute for Public Health and the Environment of
      Netherlands, have been summarized. These databases reveal that silver, titanium,
      carbon-based ENMs are the major nanomaterials associated with consumer products.
      The presence and potential release of silver, titanium, carbon-based, and other
      nanomaterials from consumer goods available in published literature are also
      summarized, as well as the potential human exposure scenarios of inhalation,
      ingestion, dermal, and combination of all means. The prospecting of nanomaterial
      in water and biosolids provides further evidence of ENM occurrence, which could
      be linked to the use of nanomaterials containing consumer goods. Finally, this
      overview provides guidelines on toxicity studies, which calls for further efforts
      to analyze the biological effects of ENMs on human beings and their exposure
      pathways in consumer products. 

PMID- 24683022
TI  - Behavioral interventions for improving dual-method contraceptive use.
AB  - BACKGROUND: Dual-method contraception refers to using condoms as well as another
      modern method of contraception. The latter (usually non-barrier) method is
      commonly hormonal (e.g., oral contraceptives) or a non-hormonal intrauterine
      device. Use of two methods can better prevent pregnancy and the transmission of
      HIV and other sexually transmitted infections (STIs) compared to single-method
      use. Unprotected sex increases risk for disease, disability, and mortality in
      many areas due to the prevalence and incidence of HIV/STI. Millions of women,
      especially in lower-resource areas, also have an unmet need for protection
      against unintended pregnancy. OBJECTIVES: We examined comparative studies of
      behavioral interventions for improving use of dual methods of contraception. Dual
      method use refers to using condoms as well as another modern contraceptive
      method. Our intent was to identify effective interventions for preventing
      pregnancy as well as HIV/STI transmission. SEARCH METHODS: Through January 2014,
      we searched MEDLINE, CENTRAL, POPLINE, EMBASE, COPAC, and Open Grey. In addition,
      we searched ClinicalTrials.gov and ICTRP for current trials and trials with
      relevant data or reports. We examined reference lists of pertinent papers,
      including review articles, for additional reports. SELECTION CRITERIA: Studies
      could be either randomized or non-randomized. They examined a behavioral
      intervention with an educational or counseling component to encourage or improve
      the use of dual methods, i.e., condoms and another modern contraceptive. The
      intervention had to address preventing pregnancy as well as the transmission of
      HIV/STI. The program or service could be targeted to individuals, couples, or
      communities. The comparison condition could be another behavioral intervention to
      improve contraceptive use, usual care, other health education, or no
      intervention.Studies had to report use of dual methods, i.e., condoms plus
      another modern contraceptive method. We focused on the investigator's assessment
      of consistent dual-method use or use at last sex. Outcomes had to be measured at
      least three months after the behavioral intervention began. DATA COLLECTION AND
      ANALYSIS: Two authors evaluated abstracts for eligibility and extracted data from
      included studies. For the dichotomous outcomes, the Mantel-Haenszel odds ratio
      (OR) with 95% CI was calculated using a fixed-effect model. Where studies used
      adjusted analysis, we presented the results as reported by the investigators. No
      meta-analysis was conducted due to differences in interventions and outcome
      measures. MAIN RESULTS: We identified four studies that met the inclusion
      criteria: three randomized controlled trials and a pilot study for one of the
      included trials. The interventions differed markedly: computer-delivered,
      individually tailored sessions; phone counseling added to clinic counseling; and
      case management plus a peer-leadership program. The latter study, which addressed
      multiple risks, showed an effect on contraceptive use. Compared to the control
      group, the intervention group was more likely to report consistent dual-method
      use, i.e., oral contraceptives and condoms. The reported relative risk was 1.58
      at 12 months (95% CI 1.03 to 2.43) and 1.36 at 24 months (95% CI 1.01 to 1.85).
      The related pilot study showed more reporting of consistent dual-method use for
      the intervention group compared to the control group (reported P value = 0.06);
      the investigators used a higher alpha (P < 0.10) for this pilot study. The other
      two trials did not show any significant difference between the study groups in
      reported dual-method use or in test results for pregnancy or STIs at 12 or 24
      months. AUTHORS' CONCLUSIONS: We found few behavioral interventions for improving
      dual-method contraceptive use and little evidence of effectiveness. A
      multifaceted program showed some effect but only had self-reported outcomes. Two
      trials were more applicable to clinical settings and had objective outcomes
      measures, but neither showed any effect. The included studies had adequate
      information on intervention fidelity and sufficient follow-up periods for change
      to occur. However, the overall quality of evidence was considered low. Two trials
      had design limitations and two had high losses to follow up, as often occurs in
      contraceptive trials. Good quality studies are still needed of carefully designed
      and implemented programs or services.

PMID- 24683025
TI  - Nanoparticle aggregation: principles and modeling.
AB  - The high surface area to volume ratio of nanoparticles usually results in highly
      reactive and colloidal instability compared to their bulk counterparts.
      Aggregation as well as many other transformations (e.g., dissolution) in the
      environment may alter the physiochemical properties, reactivity, fate, transport,
      and biological interactions (e.g., bioavailability and uptake) of nanoparticles.
      The unique properties pertinent to nanoparticles, such as shape, size, surface
      characteristics, composition, and electronic structures, greatly challenge the
      ability of colloid science to understand nanoparticle aggregation and its
      environmental impacts. This review briefly introduces fundamentals about
      aggregation, fractal dimensions, classic and extended Derjaguin-Landau-Verwey
      Overbeak (DLVO) theories, aggregation kinetic modeling, experimental
      measurements, followed by detailed discussions on the major factors on
      aggregation and subsequent effects on nanomaterial transport and reactivity. 

PMID- 24683026
TI  - Influences of nanomaterials on the barrier function of epithelial cells.
AB  - Recent advances in nanotechnology have led to exciting opportunities in medicine,
      energy, manufacturing, and other fields. Nevertheless, it is important to
      adequately assess the potential impacts of nanomaterial exposure. This chapter
      focuses on the interactions of nanomaterials with epithelial barriers in the
      lungs, intestine, kidneys, skin, and placenta. Methods for determining
      transepithelial electrical resistance and paracellular permeability are
      described. Effects on cell viability and barrier integrity depend on the chemical
      nature of the nanomaterial, nanoparticle size, surface coatings, and
      concentration. Disruption of tight junctions can affect permeability and
      interfere with normal regulatory processes of the epithelial barrier. Future
      research is needed to better understand the possibilities and the limits of novel
      approaches in nanotechnology. 

PMID- 24683027
TI  - Engineered nanoparticles induced brush border disruption in a human model of the
      intestinal epithelium.
AB  - Nanoparticles hold great promise in cell biology and medicine due to the inherent
      physico-chemical properties when these materials are synthesized on the
      nanoscale. Moreover, their small size, and the ability to functionalize the outer
      nanoparticle surface makes them an ideal vector suited to traverse a number of
      physical barriers in the human body. While nanoparticles hold great promise for
      applications in cell biology and medicine, their downfall is the toxicity that
      accompanies exposure to biological systems. This chapter focuses on exposure via
      the oral route since nanomaterials are being engineered to act as carriers for
      drugs, contrast agents for specialized imaging techniques, as well as ingested
      pigments approved by regulatory agencies for human food products. After these
      nanomaterials are ingested they have the potential to interact with a number of
      biologically significant tissues, one of which is the epithelium of the small
      intestine. Within the small intestine exists enterocytes whose principal function
      is nutrient absorption. The absorptive process is aided by microvilli that act to
      increase the surface area of the epithelium. Dense arrays of microvilli, referred
      to as the brush border, have recently been shown to undergo disruption as a
      consequence of exposure to nanomaterials. This chapter aims to set the stage for
      detailed mechanistic studies at the cell biology level concerning this newly
      emerging nanotoxicity research paradigm, as the underlying structural
      characterization responsible for the existence of microvilli have been
      elucidated. 

PMID- 24683028
TI  - Nanoparticles: cellular uptake and cytotoxicity.
AB  - Understanding the interactions of nanoparticles (NPs) with cells and how these
      interactions influence their cellular uptake is essential to exploring the
      biomedical applications of NPs, particularly for drug delivery. Various factors,
      whether differences in physical properties of NPs or variations in cell-membrane
      characteristics, influence NP-cell interactions and uptake processes. NP-cell
      membrane interactions may also influence intracellular trafficking of NPs, their
      sorting into different intracellular compartments, cellular retention, and hence
      the efficacy of encapsulated therapeutics. A crucial consideration is whether
      such interactions might cause any toxicity, starting with how NPs interact in
      transit with the biological environment prior to their interactions with targeted
      cells and tissues. Understanding the effects of various NP characteristics on
      cellular and biological processes could help in designing NPs that are efficient
      but also nontoxic. 

PMID- 24683029
TI  - Atomic force microscopy study of the interaction of DNA and nanoparticles.
AB  - The interaction between nanoparticles (NPs) and DNA plays an important role in
      the genotoxicity of NPs, and it is imperative to characterize the nano/DNA
      interactions and explore the underlying chemical mechanisms. In this chapter, we
      demonstrated systematic experimental approaches based on atomic force microscope
      (AFM), coupled with modeling computation to probe the binding activity of NPs
      with DNA and the putative genotoxicity. Using quantum dots (QDs) as a model NP,
      we examined the binding kinetics, binding isotherm, binding specificity, and
      binding mechanisms of NPs to DNA with the application of AFM. We further assessed
      the binding affinity between NPs and DNA by calculating their interaction energy
      on the basis of Derjaguin-Landau-Verwey-Overbeek (DLVO) models. The modeling
      results of binding affinity were validated by the NPs/DNA binding images
      experimentally derived by AFM. The investigation of the relationship between the
      binding affinity of five NPs ((QDs (+), QDs (-), silver NPs, hematite NPs, and
      gold NPs) for DNA with their inhibition effects on DNA replication indicated that
      NPs with a high binding affinity for DNA molecules exhibited higher inhibition on
      DNA replication. The methodology employed in this study can be extended to study
      the interaction of other NPs with DNA, which is anticipated to benefit the future
      design of safe NPs, as well as the toxicological investigations of NPs. 

PMID- 24683031
TI  - Nanomaterials: impact on cells and cell organelles.
AB  - Colloidal nanoparticles designed for the interactions with cells are very small,
      nanoscale objects usually consisting of inorganic cores and organic shells that
      are dispersed in a buffer or biological medium. By tuning the material properties
      of the nanoparticles a number of different biological applications of
      nanomaterials are enabled i.e. targeting, labelling, drug delivery, use as
      diagnostic tools or therapy. For all biological applications of nanoparticles, it
      is important to understand their interactions with the surrounding biological
      environment in order to predict their biological impact, in particular when
      designing the nanoparticles for diagnostic and therapeutic purpose. Due to the
      high surface-to-volume ratio, the surface of nanomaterials is very reactive. When
      exposed to biological fluids, the proteins and biomolecules present therein tend
      to associate with the nanoparticles' surface. This phenomenon is defined as
      biomolecular corona formation. The biomolecular corona plays a key role in the
      interaction between nanoparticles and biological systems, impacting on how these
      particles interact with biological systems on a cellular and molecular level.
      This book chapter describes the nature of the interactions at the bio-nano
      interface, shows the design strategy of nanoparticles for nanomedicine, and
      defines the concepts of biomolecular corona and biological identity of
      nanoparticles. Moreover, it describes the interaction of functionalised
      nanomaterials with cell organelles and intracellular fate of nanoparticles and it
      shows therapeutic application of gold nanoparticles as dose enhancers in
      radiotherapy. 

PMID- 24683032
TI  - Design, synthesis, and functionalization of nanomaterials for therapeutic drug
      delivery.
AB  - Nanomaterials have the potential to solve some of the toughest challenges facing
      modern medicine. Their unique optical, magnetic and chemical properties at the
      nanoscale make them different from their macroscale counterparts. Successful
      application of nanomaterials can revolutionize therapeutics, diagnostics and
      imaging in several biomedical applications. Self-assembled amphiphilic polymeric
      nanoparticles have been employed to carry poorly soluble chemotherapeutic drugs.
      Loading of anticancer chemotherapeutic drugs into self assembled polymeric
      nanoparticles have shown to increase their circulation time, tumor localization
      and therapeutic potential. This book chapter provides an introductory discussion
      to organic nanotechnologies for drug delivery. Promising advances in the field of
      nanomedicine will be discussed and an outlook to the future will be provided. 

PMID- 24683033
TI  - Preparation of nanoscale pulmonary drug delivery formulations by spray drying.
AB  - Advances in preparation technologies for nanomedicines have provided novel
      formulations for pulmonary drug delivery. Application of drugs via the lungs can
      be considered as one of the most attractive implementations of nanoparticles for
      therapeutic use due to the unique anatomy and physiology of the lungs. The
      colloidal nature of nanoparticles provides important advantages to the
      formulation of drugs, which are normally difficult to administer due to poor
      stability or uptake, partly because nanoparticles protect the drug from the
      physiological milieu, facilitate transport across biological barriers and can
      offer controlled drug release. There are numerous methods for producing
      therapeutic nanoparticles, each with their own advantages and suitable
      application. Liquid atomization techniques such as spray drying can produce
      nanoparticle formulations in a dry powder form suitable for pulmonary
      administration in a direct one-step process. This chapter describes the different
      state-of-the-art techniques used to prepare drug nanoparticles (with special
      emphasize on spray drying techniques) and the strategies for administering such
      unique formulations to the pulmonary environment. 

PMID- 24683030
TI  - Intracellular signal modulation by nanomaterials.
AB  - A thorough understanding of the interactions of nanomaterials with biological
      systems and the resulting activation of signal transduction pathways is essential
      for the development of safe and consumer friendly nanotechnology. Here we present
      an overview of signaling pathways induced by nanomaterial exposures and describe
      the possible correlation of their physicochemical characteristics with biological
      outcomes. In addition to the hierarchical oxidative stress model and a review of
      the intrinsic and cell-mediated mechanisms of reactive oxygen species (ROS)
      generating capacities of nanomaterials, we also discuss other oxidative stress
      dependent and independent cellular signaling pathways. Induction of the
      inflammasome, calcium signaling, and endoplasmic reticulum stress are reviewed.
      Furthermore, the uptake mechanisms can be of crucial importance for the
      cytotoxicity of nanomaterials and membrane-dependent signaling pathways have also
      been shown to be responsible for cellular effects of nanomaterials. Epigenetic
      regulation by nanomaterials, effects of nanoparticle-protein interactions on cell
      signaling pathways, and the induction of various cell death modalities by
      nanomaterials are described. We describe the common trigger mechanisms shared by
      various nanomaterials to induce cell death pathways and describe the interplay of
      different modalities in orchestrating the final outcome after nanomaterial
      exposures. A better understanding of signal modulations induced by nanomaterials
      is not only essential for the synthesis and design of safer nanomaterials but
      will also help to discover potential nanomedical applications of these materials.
      Several biomedical applications based on the different signaling pathways induced
      by nanomaterials are already proposed and will certainly gain a great deal of
      attraction in the near future. 

PMID- 24683034
TI  - Nanomedicine: the promise and challenges in cancer chemotherapy.

PMID- 24683035
TI  - Transgenerational effects of NMs.
AB  - Nanomaterials are present in a number of commercially available products but
      there are uncertainties as to whether the unique properties that support their
      commercial use may also pose potential health risks. Information is missing
      concerning the influence of nanomaterials on the overall reproductive outcome and
      transgenerational effects in animals and plants. To obtain this information, long
      term studies would be required using animal models phylogenetically close to
      humans and exposure conditions that reflect realistic scenarios with regard to
      dosages and admission. The nanoreprotoxicology literature published to date is
      largely descriptive in nature regarding the effects of nanoparticles. The
      mechanisms, which determine particle reproduction compatibility, are mostly
      elusive at the moment. Thus, it is recommended that future research explore the
      interactions between nanomaterials and transgenerational matter on a molecular
      level. It would, for instance, be of major importance to understand the behaviour
      of nanoparticles inside the cells but also their genotoxic and epigenetic
      effects. Recent studies have shown that intravenous and/or intra-abdominal
      administration of nanoparticles to mice results in their accumulation in the
      cells of many tissues, including the brain and the testis, suggesting that they
      easily pass through the blood-brain and blood-testis barriers. In parallel embryo
      development after exposure to nanoparticles should be comparatively investigated.
      The majority of studies on embryo toxicology have concentrated on piscine
      embryos, mostly derived from zebrafish. Plants for human food as an important
      component of the ecosystem need also to be taken into account when evaluating
      transgenerational effects of engineered nanomaterials in crops. 

PMID- 24683037
TI  - Cell wall-related proteins of unknown function: missing links in plant cell wall
      development.
AB  - Lignocellulosic biomass is an important feedstock for the pulp and paper industry
      as well as emerging biofuel and biomaterial industries. However, the
      recalcitrance of the secondary cell wall to chemical or enzymatic degradation
      remains a major hurdle for efficient extraction of economically important
      biopolymers such as cellulose. It has been estimated that approximately 10-15% of
      about 27,000 protein-coding genes in the Arabidopsis genome are dedicated to cell
      wall development; however, only about 130 Arabidopsis genes thus far have
      experimental evidence validating cell wall function. While many genes have been
      implicated through co-expression analysis with known genes, a large number are
      broadly classified as proteins of unknown function (PUFs). Recently the
      functionality of some of these unknown proteins in cell wall development has been
      revealed using reverse genetic approaches. Given the large number of cell wall
      related PUFs, how do we approach and subsequently prioritize the investigation of
      such unknown genes that may be essential to or influence plant cell wall
      development and structure? Here, we address the aforementioned question in two
      parts; we first identify the different kinds of PUFs based on known and predicted
      features such as protein domains. Knowledge of inherent features of PUFs may
      allow for functional inference and a concomitant link to biological context.
      Secondly, we discuss omics-based technologies and approaches that are helping
      identify and prioritize cell wall-related PUFs by functional association. In this
      way, hypothesis-driven experiments can be designed for functional elucidation of
      many proteins that remain missing links in our understanding of plant cell wall
      biosynthesis. 

PMID- 24683036
TI  - Stem cells and nanomaterials.
AB  - Because of their ability to self-renew and differentiate into many cell types,
      stem cells offer the potential to be used for tissue regeneration and
      engineering. Much progress has recently been made in our understanding of the
      biology of stem cells and our ability to manipulate their proliferation and
      differentiation to obtain functional tissues. Similarly, nanomaterials have been
      recently developed that will accelerate discovery of mechanisms driving stem cell
      fate and their utilization in medicine. Nanoparticles have been developed that
      allow the labeling and tracking of stem cells and their differentiated phenotype
      within an organism. Nanosurfaces are engineered that mimic the extracellular
      matrix to which stem cells adhere and migrate. Scaffolds made of functionalized
      nanofibers can now be used to grow stem cells and regenerate damaged tissues and
      organs. However, the small scale of nanomaterials induces changes in their
      chemical and physical properties that might modify their interactions with cells
      and tissues, and render them toxic to stem cells. Therefore a thorough
      understanding of stem cell-nanomaterial interactions is still necessary not only
      to accelerate the success of medical treatments but also to ensure the safety of
      the tools provided by these novel technologies. 

PMID- 24683038
TI  - Ionic-liquid-assisted synthesis of nanostructured and carbon-coated Li3V2(PO4)3
      for high-power electrochemical storage devices.
AB  - Carbon-coated Li3V2(PO4)3 (LVP) displaying nanostructured morphology can be
      easily prepared by using ionic-liquid-assisted sol-gel synthesis. The selection
      of highly viscous and thermally stable ionic liquids might promote the formation
      of nanostructures during the sol-gel synthesis. The presence of these structures
      shortens the diffusion paths and enlarges the contact area between the active
      material and the electrolyte; this leads to a significant improvement in lithium
      ion diffusion. At the same time, the use of ionic liquids has a positive
      influence on the coating of the LVP particles, which improves the electronic
      conductivity of this material; this leads to enhanced charge-transfer properties.
      At a high current density of 40 C, the LVP/N-butyl-N-methylpyrrolidinium
      bis(trifluoromethanesulfonyl)imide material delivered a reversible capacity of
      approximately 100 mA h g(-1), and approximately 99 % of the initial capacity
      value was retained even after 100 cycles at 50 C. The excellent high rate and
      cycling stability performance make Li3V2(PO4)3 prepared by ionic-liquid-assisted
      sol-gel synthesis a very promising cathode material for high-power
      electrochemical storage devices.

PMID- 24683041
TI  - Pigment-acceptor-catalyst triads for photochemical hydrogen evolution.
AB  - In order to solve the problems of global warming and shortage of fossil fuels,
      researchers have been endeavoring to achieve artificial photosynthesis: splitting
      water into H2 and O2 under solar light illumination. Our group has recently
      invented a unique system that drives photoinduced water reduction through "Z
      scheme" photosynthetic pathways. Nevertheless, that system still suffered from a
      low turnover number (TON) of the photocatalytic cycle (TON=4.1). We have now
      found and describe herein a new methodology to make significant improvements in
      the TON, up to around TON=14-27. For the new model systems reported herein, the
      quantum efficiency of the second photoinduced step in the Z-scheme photosynthesis
      is dramatically improved by introducing multiviologen tethers to temporarily
      collect the high-energy electron generated in the first photoinduced step. These
      are unique examples of "pigment-acceptor-catalyst triads", which demonstrate a
      new effective type of artificial photosynthesis. 

PMID- 24683042
TI  - Native Hawaiian views on biobanking.
AB  - Genomic science represents a new frontier for health research and will provide
      important tools for personalizing health care. Biospecimen-based research is an
      important mechanism for expanding the genomic research capacity, and indigenous
      peoples are a target of biospecimen-based research due to their relative
      isolation and the potential to discover rare or unique genotypes. This study
      explored Native Hawaiian perceptions of and expectations for biobanking. Ten
      discussion groups were conducted with Native Hawaiians (N = 92), who first heard
      a presentation on biobanking. Six themes emerged: (1) biobank governance by the
      Native Hawaiian community, (2) research transparency, (3) priority of Native
      Hawaiian health concerns, (4) leadership by Native Hawaiian scientists
      accountable to community, (5) re-consenting each time specimen is used, and (6)
      education of Native Hawaiian communities. Considered together, these findings
      suggest that biobanking should be guided by six principles that comprise
      "G.R.E.A.T. Research" (Governance, Re-consent, Education, Accountability,
      Transparency, Research priorities). These recommendations are being shared with
      biobanking facilities in Hawai'i as they develop protocols for biobanking
      participation, governance, and education. These findings also inform researchers
      and indigenous peoples throughout the world who are working on biobanking and
      genomic research initiatives in their nations. 

PMID- 24683043
TI  - Lay navigator model for impacting cancer health disparities.
AB  - This paper recounts experiences, challenges, and lessons learned when
      implementing a lay patient navigator program to improve cancer care among
      medically underserved patients who presented in a primary care clinic with a
      breast or colorectal cancer abnormality. The program employed five lay navigators
      to navigate 588 patients. Central programmatic elements were the following: (1)
      use of bilingual lay navigators with familiarity of communities they served; (2)
      provision of training, education, and supportive activities; (3)
      multidisciplinary clinical oversight that factored in caseload intensity; and (4)
      well-developed partnerships with community clinics and social service entities.
      Deconstruction of healthcare system information was fundamental to navigation
      processes. We conclude that a lay model of navigation is well suited to assist
      patients through complex healthcare systems; however, a stepped care model that
      includes both lay and professional navigation may be optimal to help patients
      across the entire continuum. 

PMID- 24683044
TI  - Modulation by metformin of molecular and histopathological alterations in the
      lung of cigarette smoke-exposed mice.
AB  - The anti-diabetic drug metformin is endowed with anti-cancer properties.
      Epidemiological and experimental studies, however, did not provide univocal
      results regarding its role in pulmonary carcinogenesis. We used Swiss H mice of
      both genders in order to detect early molecular alterations and tumors induced by
      mainstream cigarette smoke. Based on a subchronic toxicity study, oral metformin
      was used at a dose of 800 mg/kg diet, which is 3.2 times higher than the
      therapeutic dose in humans. Exposure of mice to smoke for 4 months, starting at
      birth, induced a systemic clastogenic damage, formation of DNA adducts, oxidative
      DNA damage, and extensive downregulation of microRNAs in lung after 10 weeks.
      Preneoplastic lesions were detectable after 7.5 months in both lung and urinary
      tract along with lung tumors, both benign and malignant. Modulation by metformin
      of 42 of 1281 pulmonary microRNAs in smoke-free mice highlighted a variety of
      mechanisms, including modulation of AMPK, stress response, inflammation,
      NFkappaB, Tlr9, Tgf, p53, cell cycle, apoptosis, antioxidant pathways, Ras, Myc,
      Dicer, angiogenesis, stem cell recruitment, and angiogenesis. In smoke-exposed
      mice, metformin considerably decreased DNA adduct levels and oxidative DNA
      damage, and normalized the expression of several microRNAs. It did not prevent
      smoke-induced lung tumors but inhibited preneoplastic lesions in both lung and
      kidney. In conclusion, metformin was able to protect the mouse lung from smoke
      induced DNA and microRNA alterations and to inhibit preneoplastic lesions in lung
      and kidney but failed to prevent lung adenomas and malignant tumors induced by
      this complex mixture.

PMID- 24683045
TI  - A cross-sectional study on drug use in multiple system atrophy.
AB  - BACKGROUND: Drug use has rarely been studied in multiple system atrophy (MSA)
      while such patients receive many treatments based on weak evidence. OBJECTIVE: To
      analyze drug use from the database of the French MSA Reference Center, and to
      compare it with data from patients with Parkinson disease (PD). METHODS:
      Medication of 147 MSA and 180 age- and sex-matched PD patients was analyzed.
      Motor and autonomic symptoms were explored in MSA patients by the SCOPA-Autonomic
      and Unified MSA Rating Scale (UMSARS). RESULTS: MSA and PD patients received a
      mean of five different drugs. MSA patients were more frequently exposed to
      laxatives, antidiabetic medications, antihypotensives, muscarinic antagonists,
      alpha-adrenergic blockers, and antidepressants. Levodopa consumption was less in
      MSA-C (cerebellar) patients compared with MSA-P (parkinsonian) and PD patients.
      Dopamine agonists were more consumed by PD than MSA patients. MSA patients with
      more severe disability received more laxatives, anticoagulants, and
      antidepressants. MSA-P patients received more analgesics. "Probable" MSA patients
      received more antihypotensives and less alpha-adrenergic blockers. Patients with
      higher SCOPA-Autonomic scores were more frequently on antihypotensives or
      antidepressants. Drug associations leading to potential adverse interactions were
      uncommon (usually <5%). CONCLUSIONS: Some differences in drug use between MSA and
      PD patients were observed and expected, including those used for the relief of
      parkinsonian motor symptoms, autonomic dysfunction, and depression. Many of these
      drugs are frequently used in MSA in the absence of well-established, positive,
      benefit-risk evaluations, thus calling for better assessments. The reason why
      other medications, including anti-diabetic medications, were more consumed by MSA
      patients remains unclear and deserves further exploration.

PMID- 24683040
TI  - Selenium for preventing cancer.
AB  - BACKGROUND: This review is an update of the first Cochrane publication on
      selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both
      nutritional and toxicological properties. Higher selenium exposure and selenium
      supplements have been suggested to protect against several types of cancers.
      OBJECTIVES: Two research questions were addressed in this review: What is the
      evidence for:1. an aetiological relation between selenium exposure and cancer
      risk in humans? and2. the efficacy of selenium supplementation for cancer
      prevention in humans? SEARCH METHODS: We conducted electronic searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE
      (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit
      (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals
      indexed in CancerLit, no further searches were conducted in this database after
      2004. SELECTION CRITERIA: We included prospective observational studies (cohort
      studies including sub-cohort controlled studies and nested case-control studies)
      and randomised controlled trials (RCTs) with healthy adult participants (18 years
      of age and older). DATA COLLECTION AND ANALYSIS: For observational studies, we
      conducted random effects meta-analyses when five or more studies were retrieved
      for a specific outcome. For RCTs, we performed random effects meta-analyses when
      two or more studies were available. The risk of bias in observational studies was
      assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale
      for cohort and case-control studies; the criteria specified in the Cochrane
      Handbook for Systematic Reviews of Interventions were used to evaluate the risk
      of bias in RCTs. MAIN RESULTS: We included 55 prospective observational studies
      (including more than 1,100,000 participants) and eight RCTs (with a total of
      44,743 participants). For the observational studies, we found lower cancer
      incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to
      0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6)
      associated with higher selenium exposure. Gender-specific subgroup analysis
      provided no clear evidence of different effects in men and women (P value 0.47),
      although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6)
      than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced
      decreases in risk of site-specific cancers were seen for stomach, bladder and
      prostate cancers. However, these findings have limitations due to study design,
      quality and heterogeneity that complicate interpretation of the summary
      statistics. Some studies suggested that genetic factors may modify the relation
      between selenium and cancer risk-a hypothesis that deserves further
      investigation.In RCTs, we found no clear evidence that selenium supplementation
      reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two
      studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two
      studies, N = 18,698), and this finding was confirmed when the analysis was
      restricted to studies with low risk of bias. The effect on prostate cancer was
      imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the
      analysis was limited to trials with low risk of bias, the interventions showed no
      effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non
      melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies,
      N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial
      (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns
      about possible increased risk of type 2 diabetes, alopecia and dermatitis due to
      selenium supplements. An early hypothesis generated by NPCT that individuals with
      the lowest blood selenium levels at baseline could reduce their risk of cancer,
      particularly of prostate cancer, by increasing selenium intake has not been
      confirmed by subsequent trials. As the RCT participants were overwhelmingly male
      (94%), gender differences could not be systematically assessed. AUTHORS'
      CONCLUSIONS: Although an inverse association between selenium exposure and the
      risk of some types of cancer was found in some observational studies, this cannot
      be taken as evidence of a causal relation, and these results should be
      interpreted with caution. These studies have many limitations, including issues
      with assessment of exposure to selenium and to its various chemical forms,
      heterogeneity, confounding and other biases. Conflicting results including
      inverse, null and direct associations have been reported for some cancer
      types.RCTs assessing the effects of selenium supplementation on cancer risk have
      yielded inconsistent results, although the most recent studies, characterised by
      a low risk of bias, found no beneficial effect on cancer risk, more specifically
      on risk of prostate cancer, as well as little evidence of any influence of
      baseline selenium status. Rather, some trials suggest harmful effects of selenium
      exposure. To date, no convincing evidence suggests that selenium supplements can
      prevent cancer in humans.

PMID- 24683046
TI  - Darbepoetin for the anaemia of chronic kidney disease.
AB  - BACKGROUND: Erythropoiesis-stimulating agents are used to treat anaemia in people
      with chronic kidney disease (CKD). Several agents are available including epoetin
      alfa or beta as well as agents with a longer duration of action, darbepoetin alfa
      and methoxy polyethylene glycol-epoetin beta. OBJECTIVES: To assess the benefits
      and harms of darbepoetin alfa to treat anaemia in adults and children with CKD
      (stages 3 to 5, 5D, and kidney transplant recipients). SEARCH METHODS: We
      searched the Cochrane Renal Group's Specialised Register (to 13 January 2014)
      through contact with the Trials' Search Co-ordinator using search terms relevant
      to this review. Studies contained in the Specialised Register are identified
      through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE.
      SELECTION CRITERIA: We included randomised controlled trials of any darbepoetin
      alfa treatment of at least three months duration in adults or children with CKD
      (any stage). DATA COLLECTION AND ANALYSIS: Data were extracted by two independent
      investigators. Patient-centred outcomes (need for blood transfusion, iron
      therapy, progression of kidney disease, total and cardiovascular mortality,
      cardiovascular events, cancer, hypertension, seizures, and health-related quality
      of life) and other outcomes (haemoglobin levels) were assessed using random
      effects meta-analysis. We calculated risk ratios for dichotomous outcomes and
      mean differences for continuous outcomes, both with 95% confidence intervals.
      MAIN RESULTS: We identified 32 studies comprising 9414 participants; 21 studies
      in 8328 participants could be included in our meta-analyses. One study (4038
      participants) compared darbepoetin alfa to placebo, 16 studies (2955
      participants) compared darbepoetin alfa to epoetin alfa or beta, four studies
      (1198 participants) compared darbepoetin alfa to methoxy polyethylene glycol
      epoetin beta, three studies (420 participants) compared more frequent with less
      frequent darbepoetin alfa administration and four studies (303 participants)
      compared intravenous with subcutaneous darbepoetin alfa administration.In a
      single large study, darbepoetin alfa reduced the need for blood transfusion and
      iron therapy compared with placebo in adults with CKD stage 3 to 5, but had
      little or no effect on survival, increased risks of hypertension, and had
      uncertain effects on quality of life. Data comparing darbepoetin alfa with
      epoetin alfa or beta or methoxy polyethylene glycol-epoetin beta were sparse and
      inconclusive. Comparisons of differing dosing schedules and routes of
      administration were compared in small numbers of participants and studies.
      Evidence for treatment effects of darbepoetin alfa were particularly limited for
      children with CKD, adults with CKD stage 5D, and recipients of a kidney
      transplant.Studies included in this review were generally at high or unclear risk
      of bias for all items (random sequence generation, allocation concealment,
      incomplete outcome data, blinding of participants and personnel, blinding of
      outcome assessment, selective outcome reporting, intention to treat analysis and
      other sources of bias). One large study comparing darbepoetin alfa with placebo
      was at low risk of bias for most items assessed. AUTHORS' CONCLUSIONS: Data
      suggest that darbepoetin alfa effectively reduces need for blood transfusions in
      adults with CKD stage 3 to 5, but has little or no effect on mortality or quality
      of life. The effects of darbepoetin alfa in adults with CKD stage 5D and kidney
      transplant recipients and children with CKD remain uncertain as do the relative
      benefits and harms of darbepoetin alfa compared with other ESAs (epoetin alfa or
      beta and methoxy polyethylene glycol-epoetin beta).

PMID- 24683051
TI  - Alpha2-adrenergic agonists for the management of opioid withdrawal.
AB  - BACKGROUND: Withdrawal is a necessary step prior to drug-free treatment or as the
      endpoint of long-term substitution treatment. OBJECTIVES: To assess the
      effectiveness of interventions involving the use of alpha2-adrenergic agonists
      compared with placebo, reducing doses of methadone, symptomatic medications or
      with comparison of different alpha2-adrenergic agonists, for the management of
      the acute phase of opioid withdrawal. Outcomes included the intensity of signs
      and symptoms and overall withdrawal syndrome experienced, duration of treatment,
      occurrence of adverse effects and completion of treatment. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (Issue 7, 2013),
      MEDLINE (1946 to July week 4, 2013), EMBASE (January 1985 to August week 1,
      2013), PsycINFO (1806 to July week 5, 2013) and reference lists of articles. We
      also contacted manufacturers in the field. SELECTION CRITERIA: Randomised
      controlled trials comparing alpha2-adrenergic agonists (clonidine, lofexidine,
      guanfacine, tizanidine) with reducing doses of methadone, symptomatic medications
      or placebo, or comparing different alpha2-adrenergic agonists to modify the signs
      and symptoms of withdrawal in participants who were opioid dependent. DATA
      COLLECTION AND ANALYSIS: One review author assessed studies for inclusion and
      undertook data extraction. All review authors decided on inclusion and confirmed
      the overall process. MAIN RESULTS: We included 25 randomised controlled trials,
      involving 1668 participants. Five studies compared a treatment regimen based on
      an alpha2-adrenergic agonist with placebo, 12 with a regimen based on reducing
      doses of methadone, four with symptomatic medications and five compared different
      alpha2-adrenergic agonists.Alpha2-adrenergic agonists were more effective than
      placebo in ameliorating withdrawal in terms of the likelihood of severe
      withdrawal (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.18 to 0.57, 3
      studies, 148 participants). Completion of treatment was significantly more likely
      with alpha2-adrenergic agonists compared with placebo (RR 1.95, 95% CI 1.34 to
      2.84, 3 studies, 148 participants).Alpha2-adrenergic agonists were somewhat less
      effective than reducing doses of methadone in ameliorating withdrawal symptoms,
      as measured by the likelihood of severe withdrawal (RR 1.18, 95% CI 0.81 to 1.73,
      5 studies, 340 participants), peak withdrawal score (standardised mean difference
      (SMD) 0.22, 95% CI -0.02 to 0.46, 2 studies, 263 participants) and overall
      withdrawal severity (SMD 0.13, 95% CI -0.24 to 0.49, 3 studies, 119
      participants). These differences were not statistically significant. The signs
      and symptoms of withdrawal occurred and resolved earlier with alpha2-adrenergic
      agonists. The duration of treatment was significantly longer with reducing doses
      of methadone (SMD -1.07, 95% CI -1.31 to -0.83, 3 studies, 310 participants).
      Hypotensive or other adverse effects were significantly more likely with alpha2
      adrenergic agonists (RR 1.92, 95% CI 1.19 to 3.10, 6 studies, 464 participants)
      but there was no significant difference in rates of completion of withdrawal
      treatment (RR 0.85, 95% CI 0.69 to 1.05, 9 studies, 659 participants).There were
      insufficient data for quantitative comparison of different alpha2-adrenergic
      agonists. Available data suggest that lofexidine does not reduce blood pressure
      to the same extent as clonidine, but is otherwise similar to clonidine. AUTHORS'
      CONCLUSIONS: Clonidine and lofexidine are more effective than placebo for the
      management of withdrawal from heroin or methadone. No significant difference in
      efficacy was detected for treatment regimens based on clonidine or lofexidine,
      and those based on reducing doses of methadone over a period of around 10 days
      but methadone is associated with fewer adverse effects than clonidine, and
      lofexidine has a better safety profile than clonidine.

PMID- 24683047
TI  - Prognostic significance of calcified plaque among symptomatic patients with
      nonobstructive coronary artery disease.
AB  - BACKGROUND: Coronary artery calcium (CAC) is a well-established predictor of
      clinical outcomes for population screening. Limited evidence is available as to
      its predictive value in symptomatic patients without obstructive coronary artery
      disease (CAD). The aim of the current study was to assess the prognostic value of
      CAC scores among symptomatic patients with nonobstructive CAD. METHODS: From the
      COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An
      InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with
      nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic
      angiography were prospectively enrolled and followed for a median of 2.1 years.
      Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary
      stenosis) a luminal stenosis. CAC scores were calculated using the Agatston
      method. Univariable and multivariable Cox proportional hazard models were
      employed to estimate all-cause mortality and/or myocardial infarction (MI). Four
      year death and death or MI rates were 1.9% and 3.3%. RESULTS: Of the 4,380
      patients with no luminal stenosis, 86% had CAC scores of <10 while those with a
      luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC
      score of >=100. Among patients with no luminal stenosis, CAC was not predictive
      of all-cause mortality (P = .44). However, among patients with a luminal
      stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to
      >=400 (P < .0001). The mortality hazard was 6.0 (P = .004) and 13.3 (P < .0001)
      for patients with a CAC score of 100-399 and >=400. In patients with a luminal
      stenosis, CAC remained independently predictive in all-cause mortality (P <
      .0001) and death or MI (P < .0001) in multivariable models containing CAD risk
      factors and presenting symptoms. CONCLUSIONS: CAC allows for the identification
      of those at an increased hazard for death or MI in symptomatic patients with
      nonobstructive disease. From the CONFIRM registry, the extent of CAC was an
      independent estimator of long-term prognosis among symptomatic patients with
      luminal stenosis and may further define risk and guide preventive strategies in
      patients with nonobstructive CAD.

PMID- 24683053
TI  - Voltage-driven reversible insertion into and leaving from a lipid bilayer: tuning
      transmembrane transport of artificial channels.
AB  - Three new artificial transmembrane channel molecules have been designed and
      synthesized by attaching positively charged Arg-incorporated tripeptide chains to
      pillar[5]arene. Fluorescent and patch-clamp experiments revealed that voltage can
      drive the molecules to insert into and leave from a lipid bilayer and thus switch
      on and off the transport of K(+) ions. One of the molecules was found to display
      antimicrobial activity toward Bacillus subtilis with half maximal inhibitory
      concentration (IC50 ) of 10 MUM which is comparable to that of natural channel
      forming peptide alamethicin. 

PMID- 24683054
TI  - Outpatient training in public/community psychiatry and systems-based practices.

PMID- 24683055
TI  - Social physique anxiety and disturbed eating attitudes and behaviors in
      adolescents: moderating effects of sport, sport-related characteristics, and
      gender.
AB  - BACKGROUND: The involvement of adolescents presenting high levels of social
      physique anxiety (SPA) in sport practice has been hypothesized as potentially
      problematic in terms of being associated with disturbed eating attitudes and
      behaviors (DEAB). Indeed, sport practice itself has been reported to be
      associated with higher levels of SPA and DEAB, and sport settings may sometimes
      promote unhealthy life habits. Nevertheless, current studies are few and present
      several limitations. PURPOSE: The objective of the present study was to examine
      these relationships among adolescents involved or not in various types (i.e.,
      leanness and individual) and contexts (i.e., organized and competitive) of sport
      practice. METHOD: The sample included 766 French adolescents (337 boys and 429
      girls), aged between 11 and 18 years, involved (n = 335) or not (n = 431) in
      sport practice. SPA and DEAB were assessed using French adaptations of the SPA
      scale and the Eating Attitudes Test-26. RESULTS: The results reveal a significant
      and positive association between SPA and the DEAB scales. Furthermore, they show
      a positive relationship between SPA and (a) vomiting-purging behaviors in
      adolescents involved in individual sports and (b) generic DEAB (i.e., a subscale
      covering fear of getting fat, food preoccupation, and eating-related guilt),
      particularly in adolescents involved in individual sports. CONCLUSION: The
      relationship between SPA and DEAB does not differ according to adolescents'
      involvement in sport practice or according to their involvement in organized,
      competitive, or leanness sport practice more specifically. However, higher levels
      of SPA and DEAB were observed in adolescents involved in individual sports.

PMID- 24683056
TI  - Use of interactive theater and role play to develop medical students' skills in
      breaking bad news.
AB  - Creative arts have been increasingly implemented in medical education. This study
      investigated the use of interactive theater and role play with professional
      actors in teaching breaking bad news to medical students. The objectives were to
      explore the contexts, approaches, experiences, and reactions in giving and
      receiving bad news. Second-year medical students participated in a required
      educational session that utilized interactive theater which helps students learn
      about the issues of breaking bad news to a patient with cancer. Following the
      interactive theater piece, professional actors provided students role play
      experiences in small groups with breaking bad news. Anonymous evaluation surveys
      were given out to all second-year medical students at the conclusion of the
      breaking bad news session. Surveys contained quantitative and qualitative
      responses. Three years of evaluations were analyzed. A total of 451 (88 %)
      students completed the evaluations. Comments were thematically analyzed. Ninety
      four percent agreed that the theater piece prompted reflection on patient
      provider communications, and 89 % agreed that it stimulated discussion on complex
      issues with breaking bad news. The two most common themes in student comments
      concerned the importance of realism in the theater piece, and the value of
      experiencing multiple perspectives. Use of professional actors during the role
      play exercises enhances the realism and pushed the students out of their own
      "comfort zones" in ways that may more closely approximate real life clinical
      situations. Interactive theater can be a potentially powerful tool to teach
      breaking bad news during medical school. 

PMID- 24683057
TI  - Pharmacological interventions for prevention or treatment of postoperative pain
      in people undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND: While laparoscopic cholecystectomy is generally considered less
      painful than open surgery, pain is one of the important reasons for delayed
      discharge after day-surgery and overnight stay following laparoscopic
      cholecystectomy. The safety and effectiveness of different pharmacological
      interventions such as non-steroidal anti-inflammatory drugs, opioids, and
      anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is
      unknown. OBJECTIVES: To assess the benefits and harms of different analgesics in
      people undergoing laparoscopic cholecystectomy. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      Science Citation Index Expanded, and the World Health Organization International
      Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify
      randomised clinical trials of relevance to this review. SELECTION CRITERIA: We
      considered only randomised clinical trials (irrespective of language, blinding,
      or publication status) comparing different pharmacological interventions with no
      intervention or inactive controls for outcomes related to benefit in this review.
      We considered comparative non-randomised studies with regards to treatment
      related harms. We also considered trials that compared one class of drug with
      another class of drug for this review. DATA COLLECTION AND ANALYSIS: Two review
      authors collected the data independently. We analysed the data with both fixed
      effect and random-effects models using Review Manager 5 analysis. For each
      outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95%
      confidence intervals (CI). MAIN RESULTS: We included 25 trials with 2505
      participants randomised to the different pharmacological agents and inactive
      controls. All the trials were at unclear risk of bias. Most trials included only
      low anaesthetic risk people undergoing elective laparoscopic cholecystectomy.
      Participants were allowed to take additional analgesics as required in 24 of the
      trials. The pharmacological interventions in all the included trials were aimed
      at preventing pain after laparoscopic cholecystectomy. There were considerable
      differences in the pharmacological agents used and the methods of administration.
      The estimated effects of the intervention on the proportion of participants who
      were discharged as day-surgery, the length of hospital stay, or the time taken to
      return to work were imprecise in all the comparisons in which these outcomes were
      reported (very low quality evidence). There was no mortality in any of the groups
      in the two trials that reported mortality (183 participants, very low quality
      evidence). Differences in serious morbidity outcomes between the groups were
      imprecise across all the comparisons (very low quality evidence). None of the
      trials reported patient quality of life or time taken to return to normal
      activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on
      the visual analogue scale of 1 to 10 cm in the comparisons involving the
      different pharmacological agents and inactive controls (low or very low quality
      evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a
      modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons
      involving the different pharmacological agents and inactive controls (low or very
      low quality evidence). AUTHORS' CONCLUSIONS: There is evidence of very low
      quality that different pharmacological agents including non-steroidal anti
      inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain
      scores in people at low anaesthetic risk undergoing elective laparoscopic
      cholecystectomy. However, the decision to use these drugs has to weigh the
      clinically small reduction in pain against uncertain evidence of serious adverse
      events associated with many of these agents. Further randomised clinical trials
      of low risk of systematic and random errors are necessary. Such trials should
      include important clinical outcomes such as quality of life and time to return to
      work in their assessment.

PMID- 24683058
TI  - ASD: Psychopharmacologic Treatments and Neurophysiologic Underpinnings.
AB  - Autism Spectrum Disorder encompasses a range of neurodevelopmental disorders
      characterized by early deficits in social communication in addition to restricted
      and repetitive behaviors. Symptoms are increasingly understood to be associated
      with abnormalities in the coordination of neuronal assemblies responsible for
      processing information essential for early adaptive behaviors. Pharmacologic
      treatments carry evidence for clinically significant benefit of multiple
      impairing symptoms of ASD, yet these benefits are limited and range across a
      broad spectrum of medication classes, making it difficult to characterize
      associated neurochemical impairments. Increasing prevalence of both ASD and its
      pharmacologic management calls for greater understanding of the neurophysiologic
      basis of the disorder. This paper reviews underlying alterations in local brain
      regions and coordination of brain activation patterns during both resting state
      and task-related processes. We propose that new pharmacologic treatments may
      focus on realigning trajectories of network specialization across development by
      working in combination with behavioral treatments to enhance social and emotional
      learning by bolstering the impact of experience-induced plasticity on neuronal
      network connectivity. 

PMID- 24683060
TI  - The relation between burnout and sleep disorders in medical students.
AB  - OBJECTIVE: The aim of this study is to assess the mutual relationships between
      burnout and sleep disorders in students in the preclinical phase of medical
      school. METHODS: This study collected data on 127 medical students who filled in
      the Maslach Burnout Inventory-Student Survey, Pittsburgh Sleep Quality Index,
      Epworth Sleepiness Scale, Beck Depression Inventory, and Beck Anxiety Inventory.
      Hierarchical logistic regressions tested the reciprocal influence between sleep
      disorders and burnout, controlling for depression and anxiety. RESULTS: Regular
      occurrence of emotional exhaustion, poor sleep quality, and excessive daytime
      sleepiness affected 60, 65, and 63% of medical students, respectively. Emotional
      exhaustion and daytime sleepiness influenced each other. Daytime sleep
      dysfunctions affected unidirectionally the occurrence of cynicism and academic
      efficacy. The odds of emotional exhaustion (odds ratio (OR)=1.21, 95% confidence
      interval (CI)=1.08 to 1.35) and cynicism (OR=2.47, 95% CI=1.25 to 4.90) increased
      when daytime sleepiness increased. Reciprocally, the odds of excessive daytime
      sleepiness (OR=2.13, 95% CI=1.22 to 3.73) increased when emotional exhaustion
      worsened. Finally, the odds of academic efficacy decreased (OR=0.86, 95% CI=0.75
      to 0.98) when daytime sleepiness increased. CONCLUSIONS: Burnout and sleep
      disorders have relevant bidirectional effects in medical students in the early
      phase of medical school. Emotional exhaustion and daytime sleepiness showed an
      important mutual influence. Daytime sleepiness linked unidirectionally with
      cynicism and academic efficacy.

PMID- 24683059
TI  - Benefit-risk assessment of dabigatran in the treatment of stroke prevention in
      non-valvular atrial fibrillation.
AB  - Non-valvular atrial fibrillation (NVAF) is the most common clinically significant
      cardiac arrhythmia and is a common cause of stroke. The direct thrombin inhibitor
      dabigatran etexilate is approved for a variety of indications requiring
      anticoagulation, including stroke prevention in NVAF. Dabigatran does not require
      routine monitoring and exhibits only a few drug-drug interactions; however,
      impaired renal function needs observation. The Randomized Evaluation of Long-Term
      Anticoagulation Therapy (RE-LY) study comprised about 18,000 patients with NVAF
      who received dabigatran 110 mg twice daily or 150 mg twice daily, or dose
      adjusted warfarin. Compared with warfarin, dabigatran 110 mg twice daily was
      associated with similar rates of stroke and systemic embolism, and lower rates of
      haemorrhage. Dabigatran 150 mg twice daily was associated with lower rates of
      stroke and systemic embolism but similar rates of haemorrhage. The rate of
      intracerebral haemorrhage (ICH) was significantly lower in both dabigatran arms.
      Basing on the results of the RE-LY study, the net clinical benefit balancing
      stroke against ICH has been estimated with various settings (study data, registry
      patients). In patients with low stroke risk but at high risk of bleeding, only
      dabigatran 110 mg twice daily had a positive net clinical benefit when compared
      with warfarin. In patients with higher stroke risks, both doses of dabigatran
      (110 and 150 mg twice daily) had a positive net clinical benefit even if the
      bleeding risk was high. Registry data after approval of dabigatran indicate
      similar stroke/systemic embolism and major bleeding rates with dabigatran (both
      doses) compared with warfarin. Pharmacovigilance sources prove the anticipated
      bleeding risk, but a refined analysis of such data showed that bleeding rates
      associated with dabigatran use did not appear to be higher than those associated
      with warfarin. Dabigatran confers an advantage over warfarin regarding stoke
      prevention without the burden of the surveillance of vitamin K antagonists,
      especially in patients with high stroke risk. However, in elderly patients with
      impaired renal function or considerable bleeding risks, label advice regarding
      dosing needs strict observation. 

PMID- 24683061
TI  - Modeling heat dissipation at the nanoscale: an embedding approach for chemical
      reaction dynamics on metal surfaces.
AB  - We present an embedding technique for metallic systems that makes it possible to
      model energy dissipation into substrate phonons during surface chemical reactions
      from first principles. The separation of chemical and elastic contributions to
      the interaction potential provides a quantitative description of both electronic
      and phononic band structure. Application to the dissociation of O2 at Pd(100)
      predicts translationally "hot" oxygen adsorbates as a consequence of the released
      adsorption energy (ca. 2.6 eV). This finding questions the instant thermalization
      of reaction enthalpies generally assumed in models of heterogeneous catalysis. 

PMID- 24683063
TI  - Computed tomography (CT) angiography for confirmation of the clinical diagnosis
      of brain death.
AB  - BACKGROUND: The diagnosis of death using neurological criteria (brain death) has
      profound social, legal and ethical implications. The diagnosis can be made using
      standard clinical tests examining for brain function, but in some patient
      populations and in some countries additional tests may be required. Computed
      tomography (CT) angiography, which is currently in wide clinical use, has been
      identified as one such test. OBJECTIVES: To assess from the current literature
      the sensitivity of CT cerebral angiography as an additional confirmatory test for
      diagnosing death using neurological criteria, following satisfaction of clinical
      neurological criteria for brain death. SEARCH METHODS: We performed comprehensive
      literature searches to identify studies that would assess the diagnostic accuracy
      of CT angiography (the index test) in cohorts of adult patients, using the
      diagnosis of brain death according to neurological criteria as the target
      condition. We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2012, Issue 5) and the following databases from
      January 1992 to August 2012: MEDLINE; EMBASE; BNI; CINAHL; ISI Web of Science;
      BioMed Central. We also conducted searches in regional electronic bibliographic
      databases and subject-specific databases (MEDION; IndMed; African Index Medicus).
      A search was also conducted in Google Scholar where we reviewed the first 100
      results only. We handsearched reference lists and conference proceedings to
      identify primary studies and review articles. Abstracts were identified by two
      authors. Methodological assessment of studies using the QUADAS-2 tool and further
      data extraction for re-analysis were performed by three authors. SELECTION
      CRITERIA: We included in this review all large case series and cohort studies
      that compared the results of CT angiography with the diagnosis of brain death
      according to neurological criteria. Uniquely, the reference standard was the same
      as the target condition in this review. DATA COLLECTION AND ANALYSIS: We reviewed
      all included studies for methodological quality according to the QUADAS-2
      criteria. We encountered significant heterogeneity in methods used to interpret
      CT angiography studies and therefore, where possible, we re-analysed the
      published data to conform to a standard radiological interpretation model. The
      majority of studies (with one exception) were not designed to include patients
      who were not brain dead, and therefore overall specificity was not estimable as
      part of a meta-analysis. Sensitivity, confidence and prediction intervals were
      calculated for both as-published data and as re-analysed to a standardized
      interpretation model. MAIN RESULTS: Ten studies were found including 366 patients
      in total. We included eight studies in the as-published data analysis, comprising
      337 patients . The methodological quality of the studies was overall
      satisfactory, however there was potential for introduction of significant bias in
      several specific areas relating to performance of the index test and to the
      timing of index versus reference tests. Results demonstrated a sensitivity
      estimate of 0.84 (95% confidence interval (CI) 0.69 to 0.93). The 95% approximate
      prediction interval was very wide (0.34 to 0.98). Data in three studies were
      available as a four-vessel interpretation model and the data could be re-analysed
      to a four-vessel interpretation model in a further five studies, comprising 314
      patient events. Results demonstrated a similar sensitivity estimate of 0.85 (95%
      CI 0.77 to 0.91) but with an improved 95% approximate prediction interval (0.56
      to 0.96). AUTHORS' CONCLUSIONS: The available evidence cannot support the use of
      CT angiography as a mandatory test, or as a complete replacement for neurological
      testing, in the management pathway of patients who are suspected to be clinically
      brain dead. CT angiography may be useful as a confirmatory or add-on test
      following a clinical diagnosis of death, assuming that clinicians are aware of
      the relatively low overall sensitivity. Consensus on a standard radiological
      interpretation protocol for future published studies would facilitate further
      meta-analysis.

PMID- 24683064
TI  - Macroscopic free-standing hierarchical 3D architectures assembled from silver
      nanowires by ice templating.
AB  - As macroscopic three dimensional (3D) architectures show increasing significance,
      much effort has been devoted to the hierarchical organization of 1D nanomaterials
      into serviceable macroscopic 3D assemblies. How to assemble 1D nanoscale building
      blocks into 3D hierarchical architectures is still a challenge. Herein we report
      a general strategy based on the use of ice as a template for assembling 1D
      nanostructures with high efficiency and good controllability. Free-standing
      macroscopic 3D Ag nanowire (AgNW) assemblies with hierarchical binary-network
      architectures are then fabricated from a 1D AgNW suspension for the first time.
      The microstructure of this 3D AgNW network endows it with electrical conductivity
      and allows it to be made into stretchable and foldable conductors with high
      electromechanical stability. These properties should make this kind of
      macroscopic 3D AgNW architecture and it composites suitable for electronic
      applications. 

PMID- 24683062
TI  - Exogenous (automatic) attention to emotional stimuli: a review.
AB  - Current knowledge on the architecture of exogenous attention (also called
      automatic, bottom-up, or stimulus-driven attention, among other terms) has been
      mainly obtained from studies employing neutral, anodyne stimuli. Since, from an
      evolutionary perspective, exogenous attention can be understood as an adaptive
      tool for rapidly detecting salient events, reorienting processing resources to
      them, and enhancing processing mechanisms, emotional events (which are, by
      definition, salient for the individual) would seem crucial to a comprehensive
      understanding of this process. This review, focusing on the visual modality,
      describes 55 experiments in which both emotional and neutral irrelevant
      distractors are presented at the same time as ongoing task targets. Qualitative
      and, when possible, meta-analytic descriptions of results are provided. The most
      conspicuous result is that, as confirmed by behavioral and/or neural indices,
      emotional distractors capture exogenous attention to a significantly greater
      extent than do neutral distractors. The modulatory effects of the nature of
      distractors capturing attention, of the ongoing task characteristics, and of
      individual differences, previously proposed as mediating factors, are also
      described. Additionally, studies reviewed here provide temporal and spatial
      information-partially absent in traditional cognitive models-on the neural basis
      of preattention/evaluation, reorienting, and sensory amplification, the main
      subprocesses involved in exogenous attention. A model integrating these different
      levels of information is proposed. The present review, which reveals that there
      are several key issues for which experimental data are surprisingly scarce,
      confirms the relevance of including emotional distractors in studies on exogenous
      attention.

PMID- 24683067
TI  - Direct composite resin fillings versus amalgam fillings for permanent or adult
      posterior teeth.
AB  - BACKGROUND: Amalgam has been the traditional material for filling cavities in
      posterior teeth for the last 150 years and, due to its effectiveness and cost,
      amalgam is still the restorative material of choice in certain parts of the
      world. In recent times, however, there have been concerns over the use of amalgam
      restorations (fillings), relating to the mercury release in the body and the
      environmental impact following its disposal. Resin composites have become an
      esthetic alternative to amalgam restorations and there has been a remarkable
      improvement of its mechanical properties to restore posterior teeth.There is need
      to review new evidence comparing the effectiveness of both restorations.
      OBJECTIVES: To examine the effects of direct composite resin fillings versus
      amalgam fillings for permanent posterior teeth, primarily on restoration failure.
      SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to
      22 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 22 October 2013),
      EMBASE via OVID (1980 to 22 October 2013), and LILACs via BIREME Virtual Health
      Library (1980 to 22 October 2013). We applied no restrictions on language or date
      of publication when searching the electronic databases. We contacted
      manufacturers of dental materials to obtain any unpublished studies. SELECTION
      CRITERIA: Randomized controlled trials comparing dental resin composites with
      dental amalgams in permanent posterior teeth. We excluded studies having a follow
      up period of less than three years. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures expected by The Cochrane Collaboration. MAIN
      RESULTS: Of the 2205 retrieved references, we included seven trials (10 articles)
      in the systematic review. Two trials were parallel group studies involving 1645
      composite restorations and 1365 amalgam restorations (921 children) in the
      analysis. The other five trials were split-mouth studies involving 1620 composite
      restorations and 570 amalgam restorations in an unclear number of children. Due
      to major problems with the reporting of the data for the five split-mouth trials,
      the primary analysis is based on the two parallel group trials. We judged all
      seven trials to be at high risk of bias and we analyzed 3265 composite
      restorations and 1935 amalgam restorations.The parallel group trials indicated
      that resin restorations had a significantly higher risk of failure than amalgam
      restorations (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.52 to 2.35, P
      value < 0.001 (fixed-effect model) (low-quality evidence)) and increased risk of
      secondary caries (RR 2.14, 95% CI 1.67 to 2.74, P value < 0.001 (low-quality
      evidence)) but no evidence of an increased risk of restoration fracture (RR 0.87,
      95% CI 0.46 to 1.64, P value = 0.66 (moderate-quality evidence)). The results
      from the split-mouth trials were consistent with those of the parallel group
      trials.Adverse effects of dental restorations were reported in two trials. The
      outcomes considered were neurobehavioral function, renal function, psychosocial
      function, and physical development. The investigators found no difference in
      adverse effects between composite and amalgam restorations. However, the results
      should be interpreted with caution as none of the outcomes were reported in more
      than one trial. AUTHORS' CONCLUSIONS: There is low-quality evidence to suggest
      that resin composites lead to higher failure rates and risk of secondary caries
      than amalgam restorations. This review reinforces the benefit of amalgam
      restorations and the results are particularly useful in parts of the world where
      amalgam is still the material of choice to restore posterior teeth with proximal
      caries. Though the review found insufficient evidence to support or refute any
      adverse effects amalgam may have on patients, new research is unlikely to change
      opinion on its safety and due to the decision for a global phase-down of amalgam
      (Minamata Convention on Mercury) general opinion on its safety is unlikely to
      change.

PMID- 24683066
TI  - Value-based modulation of memory encoding involves strategic engagement of fronto
      temporal semantic processing regions.
AB  - A number of prior fMRI studies have focused on the ways in which the midbrain
      dopaminergic reward system coactivates with hippocampus to potentiate memory for
      valuable items. However, another means by which people could selectively remember
      more valuable to-be-remembered items is to be selective in their use of effective
      but effortful encoding strategies. To broadly examine the neural mechanisms of
      value on subsequent memory, we used fMRI to assess how differences in brain
      activity at encoding as a function of value relate to subsequent free recall for
      words. Each word was preceded by an arbitrarily assigned point value, and
      participants went through multiple study-test cycles with feedback on their point
      total at the end of each list, allowing for sculpting of cognitive strategies. We
      examined the correlation between value-related modulation of brain activity and
      participants' selectivity index, which measures how close participants were to
      their optimal point total, given the number of items recalled. Greater
      selectivity scores were associated with greater differences in the activation of
      semantic processing regions, including left inferior frontal gyrus and left
      posterior lateral temporal cortex, during the encoding of high-value words
      relative to low-value words. Although we also observed value-related modulation
      within midbrain and ventral striatal reward regions, our fronto-temporal findings
      suggest that strategic engagement of deep semantic processing may be an important
      mechanism for selectively encoding valuable items. 

PMID- 24683068
TI  - Impact of early extubation and reintubation on the incidence of bronchopulmonary
      dysplasia in neonates.
AB  - OBJECTIVE: The objective of this study was to assess rates of bronchopulmonary
      dysplasia (BPD) and BPD/death in infants first extubated between day of life
      (DOL) 1 to 3 versus 4 to 7, 8+, and impact of reintubation. STUDY DESIGN: We
      included infants with gestational age <= 28 weeks, birth weight <= 1,000 g, and
      intubation on DOL 1. Proportional hazards regression modeled time to BPD and
      BPD/death, adjusting for potential confounders. RESULTS: Of 262 infants, 101
      (38.55%), 41 (15.65%), and 120 (45.80%) were extubated between DOL 1 to 3, 4 to
      7, and 8+, respectively. Extubation between DOL 4 to 7 and DOL 1 to 3 was
      associated with an increased hazard of developing BPD (hazard ratio [HR], 1.7;
      95% confidence interval [CI], 1.0-2.8; p < 0.05). Extubation on DOL 8+ was
      associated with a significantly increased hazard compared with extubation between
      DOL 1 to 3 (HR, 16.9; 95% CI, 10.5-27.1; p < 0.0001) and DOL 4 to 7 (HR, 10.0;
      95% CI, 6.1-16.3; p < 0.0001). Similar results were noted with BPD/death.
      Reintubation did not affect BPD and BPD/death. CONCLUSIONS: Delaying extubation
      beyond the first 3 and 7 days was associated with an increased risk of BPD and
      BPD/death. Reintubation did not impact outcomes.

PMID- 24683069
TI  - Maternal-child transfer of essential and toxic elements through breast milk in a
      mine-waste polluted area.
AB  - OBJECTIVE: To determine the daily intake of essential micronutrients and toxic
      elements through breast milk in exclusive and nonexclusive breastfed infants
      living in an area with major mine tailing deposition (n = 24), compared with a
      control area (n = 11). STUDY DESIGN: The milk volume ingested by 2 to 4 and 4 to
      6 month infants was measured by a stable isotopic method. Elements in milk,
      maternal and infant urine, and drinking water were measured by inductively
      coupled plasma mass spectrometry (ICP-MS). RESULTS: Similar breast milk volume
      and essential micronutrients intake in groups of exclusively breastfed infants,
      but more cadmium, boron, and lithium through breastfeeding in experimental area
      was found. This exposure was even higher in the nonexclusively breastfed infants,
      who also ingested more arsenic, boron, and lithium than exclusive breastfed
      infants. CONCLUSION: The use of the deuterium and the ICP-MS methods made it
      possible to evaluate the exact amount of essential and toxic elements ingested by
      infants through breast milk demonstrating that lower amount of toxic elements are
      transferred to exclusive breastfed infants compared with those who additionally
      received nonmaternal milk.

PMID- 24683070
TI  - A neonatal nurse training program in kangaroo mother care (KMC) decreases
      barriers to KMC utilization in the NICU.
AB  - OBJECTIVE: This study assessed the impact of a nurse simulation training program
      on perception of kangaroo mother care (KMC) value and transfer skill competency.
      STUDY DESIGN: An 8-item Likert scale skill survey tool and a 24-item Likert
      developmental care survey tool were used in a prospective cohort study to analyze
      perceptions of 30 neonatal nurses who underwent a comprehensive KMC simulation
      based training program. Competency skills were evaluated pretraining and tracked
      by direct observation for 6 months posttraining. Pre- and postsurvey data were
      analyzed and KMC utilization for preterm infants born at <= 34 weeks' gestation
      was determined. RESULTS: Nurses' competency in infant transfer improved,
      especially in infants receiving nasal continuous positive airway pressure or
      ventilator support, from 30 to 93% or 10 to 50%, respectively, p < 0.0001.
      Neonatal nurses' perceived KMC value increased from 50 to 100%, p < 0.001, and
      parent KMC utilization increased from 26.5 to 85.9%, p < 0.0001. Nurses' support
      for parental visitation improved from 38 to 73%, p < 0.001; discussion of KMC
      with parents on the 1st day increased from 5 to 45%, p < 0.001; and initial day
      of KMC provision improved from 18.0 +/- 2.7 to 5.6 +/- 1.2 days, p < 0.001.
      CONCLUSIONS: A comprehensive simulation-based KMC education program improved
      nurses' perception of KMC value, their competency and comfort in infant transfer
      for KMC care, and successfully promoted KMC parent utilization for the preterm
      infant in the neonatal intensive care unit.

PMID- 24683071
TI  - Effect of iodine loading on the thyroid hormone level of newborns living in
      Kayseri province.
AB  - INTRODUCTION: Excessive iodine exposure during the fetal and neonatal periods can
      lead to neonatal hypothyroidism. This study was conducted to evaluate the level
      of iodine loading among newborns living in Kayseri province. A total of 59
      newborns, who were admitted due to disorders in thyroid hormone levels, were
      included in the study. Materials and METHODS: Among the patients who applied with
      thyroid hormone dysfunction, newborns with a spot urine iodine level >= 20 MUg/dL
      were included in the study between the years 2003 and 2013. Free T3 (fT3), free
      T4 (fT4), thyroid stimulating hormone (TSH), thyroglobulin (Tg), breast milk
      iodine, thyroid ultrasonography, and control measurements of fT3, fT4, TSH, and
      Tg levels were obtained accordingly from both groups of patients who received or
      did not receive treatment. RESULTS: The average age of the patients was 15 days
      with a 36/23 girl to boy ratio. Statistically, no significant difference was
      noticed between all the girls and boys with respect to all the measured values.
      The etiologic search showed that out of 59 cases, in 18 cases (30.5%) only the
      mother and in 19 cases only the newborns (32.2%) had a history of povidone iodine
      exposure; in 8 cases both mothers and their babies had exposure to povidone
      iodine (13.6%). In 14 cases (23.7%), the source of iodine loading could not be
      determined. Levothyroxine (L-thyroxine) treatment was initiated in 56% of the
      patients (n = 33). Out of 33 patients who were under treatment with L-thyroxine,
      in 13 cases only the mother had history of povidone iodine exposure; in 12 cases,
      only the baby had a history of povidone iodine exposure; in 1 case, both mother
      and her baby had a history of povidone iodine exposure, but the etiology could
      not be found in 7 cases. CONCLUSION: The use of antiseptics-containing iodine for
      mothers before and after birth and for newborns, especially for umbilical
      cleansing, can lead to iodine loading and hypothyroidism. If transient
      hypothyroidism develops within this period, then it may not be detected promptly.
      This can later lead to retardation in psychomotor development and disorder in
      learning skills during the childhood period.

PMID- 24683072
TI  - The use of electrical cardiometry for continuous cardiac output monitoring in
      preterm neonates: a validation study.
AB  - BACKGROUND: Electrical cardiometry (EC) is a continuous noninvasive method for
      measuring cardiac output (CO), but there are limited data on premature infants.
      We evaluated the utility of EC monitoring by comparing the results obtained using
      EC to measurements of CO and systemic blood flow using echocardiography (ECHO).
      METHODS: In this prospective observational study, 40 preterm neonates underwent
      108-paired EC and ECHO measurements. RESULTS: There were correlations between EC
      CO and left ventricular output (LVO, p < 0.005) and right ventricular output
      (RVO, p < 0.005) but not with superior vena cava (r = 0.093, p = 0.177). Both RVO
      and LVO correlated with EC with and without a hemodynamically significant ductus
      arteriosus (p = 0.001 and 0.008, respectively). The level of agreement was
      decreased in infants ventilated by high-frequency oscillation ventilators (HFOV).
      The bias in HFOV was also positive compared with the negative biases found in
      other modes of ventilation. CONCLUSION: Given the correlation of EC with LVO,
      RVO, and lack of confounding effects of the ductus, our results suggest that EC
      has promise for trending CO in the preterm infant. However, given the limitations
      with mode of ventilation and the lack of correlation at low LVO values, further
      study is needed before this technology can be for routine use.

PMID- 24683073
TI  - Missed oral feeding opportunities and preterm infants' time to achieve full oral
      feedings and neonatal intensive care unit discharge.
AB  - OBJECTIVE: To examine the association of missed oral feeding opportunities among
      preterm infants with achievement of full oral feedings and length of
      hospitalization. STUDY DESIGN: A secondary analysis of clinical trial data was
      conducted. Study infants included in the analysis (N = 89) were randomized to one
      of four standardized feeding progression approaches; detailed records on all
      feedings were maintained. The proportion of oral feeding opportunities reported
      as missed due to factors unrelated to the infant's clinical condition was
      calculated for each infant. RESULTS: The proportion of missed oral feeding
      opportunities per infant ranged from 0 to 0.12; 30 infants experienced one or
      more missed oral feeding opportunity. Each 1% increase in the proportion of
      missed oral feeding opportunities extended the time to achieve full oral feeding
      by 1.45 days (p = 0.007) and time to discharge by 1.36 days (p = 0.047).
      CONCLUSION: Preterm infants' missed oral feeding opportunities may adversely
      affect feeding outcomes and extend hospitalization.

PMID- 24683074
TI  - Altered Expression of miR-518b and miR-519a in the placenta is associated with
      low fetal birth weight.
AB  - OBJECTIVES: Previous studies have suggested that the expression and function of
      placenta-specific microRNAs (miRNAs) are associated with placenta trophoblastic
      proliferation and invasion. This study investigated whether the altered
      expression of placenta-specific miRNAs was involved in the development of fetal
      growth. METHODS: Placenta tissues were obtained from pregnant women with large
      for gestational age (LGA), intrauterine growth retardation (IUGR), and
      appropriate for gestational age (AGA) infants (n = 30 in each group). Real-time
      quantitative reverse transcription-polymerase chain reaction was used to analyze
      the expression of relative placenta-specific miRNAs in human placental tissues
      from three different groups. RESULTS: Compared with the LGA and healthy control
      (AGA) groups; the expression of miR-518b was decreased, whereas miR-519a was
      significantly increased in the placentas from the IUGR group (p < 0.05).
      CONCLUSION: This study suggests that altered expression of placenta-specific
      miRNAs (miR-518b and miR-519a) may be involved in the development of IUGR.

PMID- 24683075
TI  - Antenatal noninvasive DNA testing: clinical experience and impact.
AB  - BACKGROUND: Nearly two decades ago, the discovery of circulating cell-free fetal
      DNA in maternal blood created a paradigm shift in prenatal testing. Recent
      advances in DNA sequencing technology have facilitated the rapid translation of
      DNA-based testing into clinical antenatal care. CONTENT: In this review, we
      summarize the technical approaches and current clinical applications of
      noninvasive testing using cell-free DNA in maternal plasma. We discuss the impact
      of these tests on clinical care, outline proposed integration models, and suggest
      future directions for the field. SUMMARY: The use of cell-free DNA in maternal
      blood for the detection of fetal rhesus D antigen status, fetal sex, and common
      whole chromosomal aneuploidies is now well established, although testing for
      aneuploidy is still considered screening and not diagnostic. Further advances in
      technology and bioinformatics may see future clinical applications extend to the
      noninvasive detection of fetal subchromosomal aneuploidy, single gene disorders,
      and the entire fetal genome.

PMID- 24683080
TI  - Bio-inspired photonic-crystal microchip for fluorescent ultratrace detection.
AB  - Ultratrace detection attracts great interest because it is still a challenge to
      the early diagnosis and drug testing. Enriching the targets from highly diluted
      solutions to the sensitive area is a promising method. Inspired by the fog
      collecting structure on Stenocara beetle's back, a photonic-crystal (PC)
      microchip with hydrophilic-hydrophobic micropattern was fabricated by inkjet
      printing. This device was used to realize high-sensitive ultratrace detection of
      fluorescence analytes and fluorophore-based assays. Coupled with the fluorescence
      enhancement effect of a PC, detection down to 10(-16) mol L(-1) was achieved.
      This design can be combined with biophotonic devices for the detection of drugs,
      diseases, and pollutions of the ecosystem.

PMID- 24683081
TI  - Quantifying mitotic chromosome dynamics and positioning.
AB  - The proper organization and segregation of chromosomes during cell division is
      essential to the preservation of genomic integrity. To understand the mechanisms
      that spatially control the arrangement and dynamics of mitotic chromosomes
      requires imaging assays to quantitatively resolve their positions and movements.
      Here, we will discuss analytical approaches to investigate the position-dependent
      control of mitotic chromosomes in cultured cells. These methods can be used to
      dissect the specific contributions of mitotic proteins to the molecular control
      of chromosome dynamics.

PMID- 24683097
TI  - Seeing and liking: biased perception of ambiguous figures consistent with the
      "inward bias" in aesthetic preferences.
AB  - Aesthetic preferences are ubiquitous in visual experience. Indeed, it seems
      nearly impossible in many circumstances to perceive a scene without also liking
      or disliking it to some degree. Aesthetic factors are only occasionally studied
      in mainstream vision science, though, and even then they are often treated as
      functionally independent from other aspects of perception. In contrast, the
      present study explores the possibility that aesthetic preferences may interact
      with other types of visual processing. We were inspired, in particular, by the
      inward bias in aesthetic preferences: When an object with a salient "front" is
      placed near the border of a frame (say, in a photograph), observers tend to find
      the image more aesthetically pleasing if the object faces inward (toward the
      center) than if it faces outward (away from the center). We employed similar
      stimuli, except that observers viewed framed figures that were ambiguous in terms
      of the direction they appeared to be facing. The resulting percepts were
      influenced by the frames in a way that corresponded to the inward bias: When a
      figure was placed near a frame's border, observers tended to see whichever
      interpretation was facing inward. This effect occurred for both abstract
      geometric figures (e.g., ambiguously-oriented triangles) and meaningful line
      drawings (e.g., left-facing ducks or right-facing rabbits). The match between
      this new influence on ambiguous figure perception and the previously studied
      aesthetic bias suggests new ways in which aesthetic factors may relate not only
      to what we like, but also to what we see in the first place. 

PMID- 24683099
TI  - Detecting personal familiarity depends on static frames in "thin slices" of
      behavior.
AB  - Brief glimpses of nonverbal behavior (or "thin slices") offer ample visual
      information to make reliable judgments about individuals. Previous work has
      largely focused on the personality characteristics and traits of individuals;
      however, the nature of dyadic relationships (strangers, lovers, or friends) can
      also be determined (Ambady & Gray, Journal of Personality and Social Psychology,
      83, 947-961 2002). Judgments from thin slices are known to be accurate, but the
      motion features supporting accurate performance are unknown. We explored whether
      personal familiarity was detectable within the context of "thin slices" of
      genuine interaction, as well as the invariant properties of thin-slice
      recognition. In two experiments, participants sequentially viewed two 6-s silent
      videos on each trial of an individual interacting with an unfamiliar partner; the
      other depicted the same person interacting with a personally familiar partner.
      All sequences were cropped so that only the target individual was visible. In
      Experiment 1, participants viewed either the original sequences, reversed
      sequences, a static-image "slideshow" of the sequence, or a static-image
      slideshow with blank frames separating the images. In Experiment 2, all
      participants viewed the original sequences and clips played at either double
      speed or half speed. Participants' performance was above chance in the forward
      and reverse conditions, but was significantly better in both the static-image
      slideshow conditions. When task speed was manipulated, we found a larger
      performance cost for fast than for slow videos. Detecting personal familiarity
      via spontaneous natural gestures depends on information in static images more
      than on face or body movement. Although static images are typically less
      important for recognizing nonverbal behavior, we argue they may be valuable for
      making familiarity judgments from thin slices. 

PMID- 24683100
TI  - Biological effects of insulin and its analogs on cancer cells with different
      insulin family receptor expression.
AB  - Hyperinsulinemia is a likely cause of the increased cancer incidence and
      mortality in diabetic patients, but its role is difficult to define in vivo.
      Previous in vitro studies testing the mitogenic potential of insulin and its
      analogs provided incomplete and sometimes contradictory results. To better
      evaluate cancer cell responsiveness to insulin, to its analogs and to IGF-I, we
      measured under identical experimental conditions cell proliferation,
      invasiveness, and foci formation in six cancer cell lines with different insulin
      receptor family expression levels. The cancer cells studied have a different
      expression of insulin receptor (IR), its isoforms (IR-A and IR-B), and of the IGF
      I receptor. The data indicate that insulin stimulates proliferation in all cancer
      cell lines, invasiveness in some, and foci formation in none. Cancer cell
      responses to insulin (and IGF-I) are not related to receptor expression levels;
      moreover, hormone-stimulated proliferation and invasiveness are not correlated.
      IGF-I is a more potent stimulator than insulin in most but not all cancer cell
      lines. Insulin analogs including M1 and M2 Glargine metabolites stimulate cancer
      cells similar to insulin. However, exceptions occur for specific analogs in
      particular cancer cells. In conclusion, in vitro insulin is an effective growth
      factor for all cancer cells but the biological response to insulin cannot be
      predicted on the basis of receptor expression levels. In the clinical setting,
      these observations should be taken in account when deciding treatment for
      diabetic patients who are at risk of undiscovered cancer or survivors of
      oncological diseases.

PMID- 24683098
TI  - Discovering your inner Gibson: reconciling action-specific and ecological
      approaches to perception-action.
AB  - Both the action-specific perception account and the ecological approach to
      perception-action emphasize the role of action in perception. However, the action
      specific perception account demonstrates that different percepts are possible
      depending on the perceiver's ability to act, even when the same optical
      information is available. These findings challenge one of the fundamental claims
      of the ecological approach--that perception is direct--by suggesting that
      perception is mediated by internal processes. Here, we sought to resolve this
      apparent discrepancy. We contend that perception is based on the controlled
      detection of the information available in a global array that includes higher
      order patterns defined across interoceptive and exteroceptive stimulus arrays.
      These higher-order patterns specify the environment in relation to the perceiver,
      so direct sensitivity to them would be consistent with the ecological claims that
      perception of the environment is direct and animal-specific. In addition, the
      action-specific approach provides further evidence for the theory of affordances,
      by demonstrating that even seemingly abstract properties of the environment, such
      as distance and size, are ultimately perceived in terms of an agent's action
      capabilities.

PMID- 24683101
TI  - YouTube and pediatric surgery. What is the danger for parents?
AB  - Internet became one of the most important sources of public health informations
      especially for relatives and/or caregivers of sick children. Use of YouTube as a
      source of information in pediatric surgery has not been evaluated. In this study,
      we want to evaluate the use of YouTube as a source of information about one of
      the most frequent surgical urgency in pediatric patients, the acute appendicitis,
      to evaluate the risks for patients and parents. 

PMID- 24683102
TI  - Steroid instillation for idiopathic urethritis in children: an 8-year experience.
AB  - PURPOSE: Idiopathic urethritis (IU) in children is of unknown etiology and
      treatment options are limited. We aim to report our experience with steroid
      instillation in IU in children. METHODS: Retrospective data collection of all
      male children diagnosed with IU over a period of 8 years. Patients with balanitis
      xerotica obliterans (BXO) and positive urine culture at presentation were
      excluded from the study. Data were collected on patient demographics, laboratory
      and radiological investigations, cystoscopy findings, management, and outcomes.
      RESULTS: A total of 16 male children were diagnosed with IU. The mean age was
      11.6 (7-16) years. Presenting symptoms included dysuria in 10; frank hematuria in
      7; loin pain in 5; and scrotal pain in 2 patients. Serum C-reactive protein and
      full blood count was tested in 13 patients and was within normal limits in all of
      them. Endoscopy findings included posterior urethritis in 12, anterior urethritis
      in 2, and urethral stricture with inflammation in 2 patients. Ten patients
      required more than one episode of steroid instillation. Mean follow-up was 19.4
      (1-74) months. Complete resolution of symptoms and signs occurred in 15 (93.6%)
      patients and improvement of symptoms and signs noted with ongoing treatment in 1
      (6.4%) patient. CONCLUSION: IU in children can be successfully managed with
      steroid instillation. In our series, 93.6% of children had complete resolution of
      symptoms.

PMID- 24683103
TI  - Closure of large meningomyelocele wound defects with subcutaneous based pedicle
      flap with bilateral V-Y advancement: our experience and review of literature.
AB  - BACKGROUND: Meningomyelocele is a defect of the spinal cord, vertebrae, and the
      overlying skin and is the most common form of open spinal dysraphism. Rapid
      closure of the back defect in the early postnatal period is mandatory to reduce
      the frequency of infection-related complications of the central nervous system.
      Majority of the cases present with small defects, which can be closed primarily,
      with or without subcutaneous dissection. However, direct closure is not possible
      in 25% of the cases. Different types of local flaps (skin or muscle flaps) are
      widely used for covering the skin defects; and with varying results. PATIENTS AND
      METHODS: A prospective nonrandomized study was conducted in the department of
      pediatric surgery at a tertiary hospital, from September 2007 to October 2011.
      Overall 35 patients with large meningomyelocele defects that could not be closed
      primarily were included in the study. All patients were treated using
      subcutaneous tissue based pedicle flap with bilateral V-Y advancement. RESULTS:
      There were 27 neonates, 7 infants, and 1 child, with a male:female ratio of
      1.19:1. There were 3 thoracolumbar, 14 lumbar, 14 lumbosacral, 3 sacral, and 1
      multiple meningomyelocele defects with an average size of 8.5 cm (range 6.5-11
      cm). Average intraoperative blood loss was 8 mL (range 6-10.5 mL). Average
      operative time which included flap reconstruction time, after closure of dura,
      was 38.6 min. Total seven patients had wound complications viz. fat necrosis (n =
      2), flap necrosis (n = 2), hematoma (n = 1), cerebrospinal fluid leak followed by
      wound dehiscence (n = 1), wound infection which led to meningitis (n = 1).
      Average healing time for flap repair was 7.52 days. Overall 80% (n = 28) of the
      patients had good flap texture and contour with satisfactory cosmesis.
      CONCLUSION: Closure of large meningomyelocele wound defects with subcutaneous
      based pedicle flap with bilateral V-Y advancement is an effective technique. The
      main advantages of this technique are its simplicity, short operative time, good
      tolerance, early healing, and good cosmetic outcome with an excellent flap
      texture and contour match with minimal complications.

PMID- 24683104
TI  - Compliance with surgical antibiotic prophylaxis guidelines in pediatric surgery.
AB  - INTRODUCTION: Surgical antibiotic prophylaxis (AP) guidelines balance the need to
      prevent infection with the risks of adverse drug effects. Our aim was to assess
      compliance with AP guidelines. METHODS: A retrospective study was performed in a
      pediatric medical center. Included were patients aged 0 to 18 years that
      underwent clean-contaminated surgery during a 1-year period (2008-2009) and
      required AP. Compliance with four AP bundle guidelines was evaluated. Risk
      factors for noncompliance were identified using univariate and multivariate
      analyses. RESULTS: AP was given to 239 of 247 (96.8%) of patients. Complete
      compliance with AP guidelines was achieved in 16 of 247 (6.5%) patients.
      Compliance with guidelines for appropriate antibiotic, drug dose, correct timing,
      and treatment duration were found in 97.1, 52.2, 31.9, and 35.9% of patients,
      respectively. Multivariable analysis showed that inappropriate timing was
      associated with age >= 4 years (p = 0.002), urgent surgery (p = 0.0018), surgical
      department AP administration (p = 0.0001), and night-time surgery (p = 0.015).
      Incorrect AP dose was associated with presence of comorbidities (p = 0.006). No
      risk factor was related to incorrect AP duration. CONCLUSIONS: We have found a
      low rate of full compliance with AP guidelines. AP should only be given in the
      operating room. Increased awareness to AP guidelines is needed.

PMID- 24683105
TI  - Pretransplant levels of endotoxin can predict the risk of bacterial infections
      and graft liver function after liver transplantation.
AB  - BACKGROUND: Although endotoxin (Et) has been used as a biological index of
      bacterial infections, Et can also be used to evaluate liver functions because Et
      present in the portal vein blood is processed by the hepatic reticuloendothelial
      system. In the field of posttransplant management, it is important for liver
      transplant recipients to monitor the presence of posttransplant bacterial
      infections and graft liver functions because these results are directly
      correlated with a graft prognosis. Therefore, the measurement of Et during liver
      transplantation (LT) may be the detection of posttransplant infections and graft
      liver functions. This retrospective study investigated whether Et measured by the
      Et activity assay (EAA) in the peripheral venous blood during living donor LT
      (LDLT) can predict the incidence of posttransplant bacterial infections and graft
      liver functions. MATERIALS AND METHODS: The study subjects consisted of 21
      patients who underwent LDLT between April 2010 and February 2011. Et activity
      (EA) was measured using the EAA in peripheral venous blood samples collected 1 or
      2 days before LDLT, and on postoperative days (PODs) 1, 5, 7, and 14. We included
      LDLT recipients with intra-abdominal infections, respiratory infections, and
      bacteremia in the group with posttransplant bacterial infections. RESULTS: The
      incidence rates of posttransplant bacterial infections or hyperbilirubinemia
      after LDLT were 57.1%. The LDLT recipients with posttransplant bacterial
      infections or hyperbilirubinemia had significantly higher levels of EA in
      comparison with patients without complications before LDLT (0.22 +/- 0.10 vs.
      0.07 +/- 0.05, p < 0.001), but they had no statistically significant increase of
      EA between PODs 1 and 14. Based on a receiver operating characteristic curve
      analysis of pretransplant levels of EA in patients with posttransplant bacterial
      infections or hyperbilirubinemia, the recommended cutoff value to diagnose
      posttransplant bacterial infections or hyperbilirubinemia was set at 0.16
      (sensitivity 83.3%, specificity 88.9%, and area under the curve 0.940).
      CONCLUSION: At a pretransplant level of EA greater than 0.16, patients had an
      augmented risk for developing posttransplant bacterial infections or
      hyperbilirubinemia.

PMID- 24683106
TI  - Histopathological changes at colonic anastomotic site after ischemia reperfusion
      injury: role of aminoguanidine in experimental model.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) has a significant role in
      ischemia reperfusion (I-R) injury. I-R injury impairs the healing at the
      intestinal anastomotic site. This study was designed to assess the role of
      aminoguanidine (AG, a selective inhibitor of iNOS), in healing at the colonic
      anastomotic site after intestinal I-R injury in rats. Methods: Female Wistar rats
      (n = 60) were divided into three groups. Group I (n = 15): sham operation, Group
      II (n = 15): I-R injury and anastomosis, and Group III (n = 30): I-R injury +
      anastomosis + AG-50 mg/kg. On the 7th postoperative day, relaparotomy was done
      and 4 cm of the colon with an intact area of the anastomosis was resected.
      Bursting pressure and histology at the anastomotic site were assessed. RESULTS:
      The bursting pressure was significantly higher in Group III. In addition,
      bridging parameters (i.e., mucosal continuity, muscular continuity, re
      epithelization, and granulation tissue), collagen pattern, and collagen density
      were significantly better in Group III. While the polymorphonuclear density was
      higher in Group II, suggestive of delayed healing. CONCLUSION: AG, by decreasing
      inflammation and increasing collagen content in an organized pattern, helped in
      preventing I-R injury at the site of colonic anastomosis in rats.

PMID- 24683107
TI  - Should we routinely test for chordee in patients with distal hypospadias?
AB  - OBJECTIVES: The aim of this study was to determine the incidence of chordee in
      distal hypospadias and compare our intraoperative findings with those reported by
      the families of patients and to determine if routine testing for chordee should
      be performed in patients with distal hypospadias. MATERIAL AND METHODS: Surgical
      reports and medical files of distal hypospadias patients operated from January
      2008 to January 2013 were prospectively reviewed. The type of hypospadias,
      family's report of chordee, intraoperative finding of chordee and its degree were
      noted. All patients were tested for chordee intraoperatively after degloving.
      RESULTS: A total of 156 patients of which 27 had glandular, 61 coronal, and 68
      subcoronal hypospadias were included in the study. Chordee was found in 52
      patients (33.3%) intraoperatively, whereas only 15 families (9.6%) reported
      chordee preoperatively. CONCLUSION: There is risk of chordee in patients with
      distal hypospadias that needs to be accurately identified and corrected. Families
      are not always aware of the presence of chordee.

PMID- 24683108
TI  - Management of recurrent tracheoesophageal fistulas: a systematic review.
AB  - INTRODUCTION: The management of a recurrent tracheoesophageal fistula (RTEF)
      includes either open surgery (OS) or an endoscopic treatment (ET); the ideal
      option is unclear. We aim to comparatively review all published treatment
      options, and outcomes, for managing RTEF. MATERIALS AND METHODS: A literature
      search was performed using the keywords "recurrent tracheoesophageal fistula."
      All English language articles describing the management of RTEF in children were
      reviewed. A synthesis of the relevant data is presented in a descriptive form due
      to the heterogeneity of the included articles. RESULTS: A total of 44 papers
      between 1955 and 2013 described 165 patients; 57 ET and 108 OS. Of the 57 ET
      patients, there was an 84% success rate compared with 93.5% of 108 OS patients;
      the failed ET cases were all successfully treated by OS. The refistulation rate
      after OS was 21% and an average of 1.1 (range 1-2) procedures were required.
      After ET, the refistulation rate was 63% and an average of 2.1 (range 1-6)
      treatments were required for success; these results were reported after a maximum
      follow-up of 9 years and 23 years for ET and OS, respectively. The major
      complications after OS were 17 (16%) leaks and 4 (3.7%) deaths, while for ET 3
      (5%) suffered respiratory distress postoperatively and there was 1 (1.7%) death.
      CONCLUSION: OS for RTEF has a low morbidity and mortality, a higher success rate,
      and requires fewer treatments than an endoscopic repair. The ideal ET is
      undecided but it remains a viable alternative provided treatment failures are
      anticipated and prompt redo treatments initiated to prevent ongoing respiratory
      morbidity.

PMID- 24683109
TI  - The compressibility of pH-sensitive microgels at the oil-water interface: higher
      charge leads to less repulsion.
AB  - pH-responsive microgels are unique stabilizers for stimuli-sensitive emulsions
      that can be broken on demand by changing the pH value. However, recent
      experiments have indicated that electrostatic interactions play a different role
      to that in conventional Pickering emulsions. The influence of charges on the
      interactions between microgels at the oil-water interface is now described.
      Compression isotherms of microgels with different charge density and architecture
      were determined in a Langmuir trough, and counter-intuitive results were
      obtained: Charged microgels can be compressed more easily than uncharged
      microgels. The compressibility of microgels is thus not determined by direct
      Coulomb repulsion. Instead, the different swelling of the microgels in the
      charged and the uncharged states is proposed to be the key parameter. 

PMID- 24683129
TI  - jsPsych: a JavaScript library for creating behavioral experiments in a Web
      browser.
AB  - Online experiments are growing in popularity, and the increasing sophistication
      of Web technology has made it possible to run complex behavioral experiments
      online using only a Web browser. Unlike with offline laboratory experiments,
      however, few tools exist to aid in the development of browser-based experiments.
      This makes the process of creating an experiment slow and challenging,
      particularly for researchers who lack a Web development background. This article
      introduces jsPsych, a JavaScript library for the development of Web-based
      experiments. jsPsych formalizes a way of describing experiments that is much
      simpler than writing the entire experiment from scratch. jsPsych then executes
      these descriptions automatically, handling the flow from one task to another. The
      jsPsych library is open-source and designed to be expanded by the research
      community. The project is available online at www.jspsych.org . 

PMID- 24683126
TI  - Gait changes with anti-dementia drugs: a prospective, open-label study combining
      single and dual task assessments in patients with Alzheimer's disease.
AB  - BACKGROUND: No comparison of anti-dementia drugs-related gait changes has been
      previously conducted combining single and dual task assessments. OBJECTIVES: (1)
      To quantify and compare gait changes among patients with possible or probable
      Alzheimer's disease before and after the use of acetylcholinesterase inhibitors
      (i.e., donepezil, galantamine, rivastigmine) or memantine, and among controls
      with possible or probable Alzheimer's disease using no anti-dementia drugs; and
      (2) to determine whether gait changes differed between acetylcholinesterase
      inhibitors and memantine. METHODS: A total of 86 patients with mild-to-moderate
      possible or probable Alzheimer's disease were included in this quasi-experimental
      study (19 patients using acetylcholinesterase inhibitors, 36 patients using
      memantine and 31 age- and gender-matched patients without anti-dementia drugs).
      Mean values and coefficient of variation of walking speed and stride time were
      measured with the GAITRite((r)) system while usual walking and while walking with
      backward counting. RESULTS: In single task, patients using memantine had a
      greater decrease in coefficient of variation of stride time (-2.3 %) compared to
      those using acetylcholinesterase inhibitors (1.3 %, P = 0.043) and no anti
      dementia drugs (1.6 %, P = 0.026). In dual task, patients using
      acetylcholinesterase inhibitors had a greater decrease in coefficient of
      variation of stride time (-5.5 %) compared to those using memantine (2.0 %, P =
      0.002) and no anti-dementia drugs (4.1 %, P = 0.05). CONCLUSIONS: Our findings
      showed a double dissociation in the effect of anti-dementia drugs on gait
      variability in patients with possible or probable Alzheimer's disease: memantine
      improves gait variability while single tasking, whereas acetylcholinesterase
      inhibitors improves gait variability while dual tasking.

PMID- 24683130
TI  - Controlled electropolymerization of ruthenium(II) vinylbipyridyl complexes in
      mesoporous nanoparticle films of TiO(2).
AB  - Surface-initiated, oligomeric assemblies of ruthenium(II) vinylpolypyridyl
      complexes have been grown within the cavities of mesoporous nanoparticle films of
      TiO2 by electrochemically controlled radical polymerization. Surface growth was
      monitored by cyclic voltammetry as well as UV/Vis and X-ray photoelectron
      spectroscopy. Polymerization occurs by a radical chain mechanism following cyclic
      voltammetry scans to negative potentials where reduction occurs at the pi* levels
      of the polypyridyl ligands. Oligomeric growth within the cavities of the TiO2
      films occurs until an average of six repeat units are added to the surface-bound
      initiator site, which is in agreement with estimates of the internal volumes of
      the pores in the nanoparticle films. 

PMID- 24683131
TI  - Microsurgical transfer of the proximal tibia, including epiphysis, in the
      management of high above knee amputations.

PMID- 24683132
TI  - Surgical anatomy of the hypoglossal nerve for facial nerve reconstruction
      research in swine.

PMID- 24683133
TI  - pi-shaped lymphaticovenular anastomosis: the venous flow sparing technique for
      the treatment of peripheral lymphedema.
AB  - BACKGROUND: Nowadays, lymphaticovenular anastomosis has been recognized as an
      efficient microsurgical treatment for peripheral lymphedema. The technique based
      on two end-to-side anastomosis is named pi-shaped lymphaticovenular anastomosis.
      This is the venous flow-sparing technique, in which the distal endothelial cells
      are not sacrificed. The purpose of this study is to evaluate the clinical results
      of pi-shaped lymphaticovenular anastomosis in chronic lymphedema of the upper and
      lower limbs. PATIENTS AND METHODS: From November 2010 to August 2011, 20 patients
      with a peripheral lymphedema were treated by pi-shaped lymphaticovenular
      anastomosis. A total of 12 patients had a lymphedema of the upper limb and 8
      patients had a lymphedema of the lower limb. The mean age of the patients was
      57.2 years (range, 44-78 years). The mean duration of lymphedema was 6.2 years
      (range, 1-23 years). The Campisi clinical stage range 2 to 5 (average, 3.3).
      Every patient was operated under local anesthesia. Four pi-shaped
      lymphaticovenular anastomoses were performed per limb. RESULTS: The mean caliber
      of lymphatic vessels used for lymphaticovenular anastomosis was 0.55 mm (range,
      0.3-0.8 mm). The mean caliber of subdermal venules was 1.2 mm (range, 0.5-2.1
      mm).The average operative time to perform one pi-shaped lymphaticovenular
      anastomosis was 55 minutes (range, 45-65 minutes). A venous backflow was found in
      98 lymphaticovenular anastomosis (55.7%). Total 16 patients (80%) had a
      clinically significant circumferential reduction after surgery. The average
      volume differential reduction rate was 22.9% (range, 4.9-46.3) (p < 0.001).
      CONCLUSIONS: pi-Shaped lymphaticovenular anastomosis is a supermicrosurgical
      method with a low morbidity to treat peripheral lymphedema. The procedure can
      easily be performed under local anesthesia, and the postoperative recovery is
      short. The results of this series demonstrate a clinical efficiency of the
      technique to reduce chronic lymphedema of the limbs.EBM level IV.

PMID- 24683134
TI  - Secondary nerve lengthening to obtain full knee extension in popliteal pterygium
      syndrome.
AB  - Microsurgical nerve lengthening was performed in two siblings presenting a
      popliteal pterigium syndrome with a knee flexion contracture of 80 degrees. After
      the first attempt for nerve lengthening and knee extension elsewhere, a repeated
      lengthening was required due to continuing tip-toe walking and recurrent knee
      contracture at the age of 3 years. An extensive external and internal
      interfascicular microsurgical neurolysis resulted in a lengthening of the nerves.
      A full length of leg procedure had to be performed, inclusive of Achilles tendon
      lengthening to obtain a complete extension of the knee and a 90-degree ankle
      flexion. Maintaining the leg in a fully extended position was obtained with a
      dynamic splinting in the first month after the operation. When timing the
      operation we have to consider the importance of adequate precision of the
      microsurgical neurolysis, down to the identification of the Fontana bands, and
      the adequate postoperative splinting. 

PMID- 24683135
TI  - Comparison between flexible collagen and vein conduits used for size-discrepant
      nerve repair: an experimental study in rats.
AB  - Primary nerve repair is the gold standard in nerve reconstruction. When primary
      repair is not possible for injured nerves, conduit-assisted repair methods are
      frequently used. As conduits, autologous vein segments or allogenic biodegradable
      products can be used. However, their effectiveness when used in a nerve defect
      where a size discrepancy exists has not been compared. In this study, either a
      vein graft or a synthetic collagen conduit was used to bridge 10-mm defects
      between size-discrepant tibial and peroneal nerves in a rat model. After 90 days,
      nerve regeneration was evaluated using electrophysiological and histological
      methods. It can be concluded based on the results of this study that bridging a
      10-mm nerve gap with synthetic collagen conduits and autologous vein grafts
      yielded similar results in small-to-large nerve coaptations, with the vein graft
      being slightly more effective. 

PMID- 24683136
TI  - Survival and secondary surgery following lower extremity replantation.
AB  - BACKGROUND:  The limited and inconsistent literature exists on survival and
      secondary surgery following lower limb replantation. The purpose of this study
      was to review our institutional experience in lower extremity replantation to
      quantify survival and characterize secondary surgeries. METHODS:  We performed a
      retrospective chart review of all lower extremity replantations at our
      institution between 2000 and 2012. The mean follow-up period was 2.6 years.
      Patient, injury, and surgical demographics as well as replantation survival,
      secondary surgical procedures, and complications were recorded. RESULTS:  A total
      of 22 lower extremity replantations were performed with 45% survival (n = 10).
      Secondary surgeries were common with an average of six per patient (range 2-11).
      Early secondary procedures included debridements (19 of 22 patients, 86%) and
      soft tissue coverage (15 of 22 patients, 68%). The average initial
      hospitalization was 45 days (range 19-90) and time to final secondary procedure
      in patients with surviving replantation was 1.5 years (range 18 d-3.5 y). Late
      secondary surgeries were aimed at either aesthetic or functional enhancement. The
      most common complication was deep infection in 18 of 22 patients (82%) and
      infection was felt to be the cause of replantation failure in all cases.
      CONCLUSION:  We found a modest survival following lower extremity replantation
      with several secondary surgeries in each case. Infection complicated the majority
      of cases and free tissue transfer was often required for wound coverage. Early
      secondary surgeries were aimed at debridement and soft tissue coverage while late
      secondary surgeries were aimed at either aesthetic or functional enhancement.

PMID- 24683137
TI  - Pre-expanded thoracodorsal artery perforator-based flaps for repair of severe
      scarring in cervicofacial regions.
AB  - BACKGROUND: Reconstruction of cervicofacial scarring continues to present
      challenges for surgical treatment. Here we present our clinical experience in
      repairing cervicofacial scarring using pre-expanded thoracodorsal artery
      perforator flaps. METHODS: From January 2007 to December 2012, 15 patients were
      treated for severe cervicofacial scarring. In the first surgical stage, expanders
      were implanted subcutaneously in the zone nourished by thoracodorsal artery
      perforators. The expansion generally took 3 to 6 months. In the second surgical
      stage, the cervicofacial cicatricial contracture was released and the secondary
      defect was covered with local flaps. The remaining wound was covered by the free
      thoracodorsal artery perforator expanded flap, which was anastomosed to the
      facial vascular bundle. The donor site was closed directly in all the patients.
      RESULTS: The postoperative follow-up time ranged from 1 to 5 years. The
      deformities were corrected, all flaps survived completely and none were bulky.
      The maximum length of the flaps was 32 cm (mean, 22.4 +/- 4.2 cm), and the
      maximum width was 17 cm (mean, 14.4 +/- 2.2 cm). All patients exhibited recovery
      of neck movement, and there was no recurrence of neck contracture. CONCLUSION:
      The pre-expanded thoracodorsal artery perforator flap is an ideal method for
      reconstruction of severe cervicofacial cicatricial contracture.

PMID- 24683138
TI  - Intercostal nerve transfer to neurotize the musculocutaneous nerve after
      traumatic brachial plexus avulsion: a comparison of two, three, and four nerve
      transfers.
AB  - The purpose of this study was to compare the outcomes of different numbers of
      intercostal nerve (ICN) transfers for elbow flexion and to determine whether age,
      body mass index (BMI), type of injury, and preoperative delay influence the
      outcomes. From 2004 to 2010, 32 (30 included) consecutive patients underwent ICN
      transfer to the musculocutaneous nerve following brachial plexus injury. Elbow
      flexion strength was evaluated according to the British Medical Research Council
      (BMRC) grading system. Of nine patients who received two ICN transfers, six
      (66.7%) recovered with useful elbow flexion compared with 14 of 17 (82.4%)
      patients who received three ICN transfers. Of the four patients with four ICN
      transfers, three (75%) achieved useful recovery. Statistical analysis showed no
      significant difference. There is no significant difference among the outcomes of
      two, three, and four ICN transfers to the musculocutaneous nerve. Two ICN
      transfers are sufficient for useful recovery of elbow flexion. Younger patients
      achieve better results. 

PMID- 24683155
TI  - Esterified xylo-oligosaccharides for stabilization of Tween 80-stabilized oil-in
      water emulsions: stabilization mechanism, rheological properties, and stability
      of emulsions.
AB  - BACKGROUND: Amphiphilic oligosaccharides have hydrophilic and hydrophobic
      subregions; therefore they can act like surfactants, while maintaining the
      viscous properties of the starting materials as stabilizers in emulsions. In the
      present work, xylo-oligosaccharides were modified by enzymatic esterification.
      Their emulsifying and stabilizing properties may improve the stability of
      emulsions, which could be explained by rheological properties. RESULTS: The
      degree of substitution (DS) of esterified xylo-oligosaccharide ranged between
      0.042 and 0.066. The esterified xylo-oligosaccharide was adsorbed on to the
      surface of the oil droplets. The critical flocculation concentrations (CFCs) of
      Tween 80-stabilized emulsions containing native and esterified xylo
      oligosaccharide were 140 and 190 g kg(-1) , respectively. At concentrations below
      CFC, no creaming or flocculation was observed and the flow behavior of emulsions
      was Newtonian. At concentrations above CFC, emulsions containing native and
      esterified xylo-oligosaccharide showed extensive flocculation of emulsion
      droplets; consequently, shear-thinning flow behavior was expressed. Further
      increases in the concentration improved the creaming stability. The concentration
      and type of esterified xylo-oligosaccharide influenced the rate of creaming,
      whereas flow behavior of emulsions containing esterified xylo-oligosaccharide was
      clearly induced by concentration. CONCLUSION: Esterified xylo-oligosaccharides
      have potential as emulsifiers and stabilizers, since they extended the CFC and
      were more effective in preventing creaming, compared with the native species.

PMID- 24683156
TI  - Iron-catalyzed 1,2-addition of perfluoroalkyl iodides to alkynes and alkenes.
AB  - Iron catalysis has been developed for the intermolecular 1,2-addition of
      perfluoroalkyl iodides to alkynes and alkenes. The catalysis has a wide substrate
      scope and high functional-group tolerance. A variety of perfluoroalkyl iodides
      including CF3 I can be employed. The resulting perfluoroalkylated alkyl and
      alkenyl iodides can be further functionalized by cross-coupling reactions. This
      methodology provides a straightforward and streamlined access to
      perfluoroalkylated organic molecules. 

PMID- 24683159
TI  - [Infantile swallowing].
AB  - BACKGROUND: Increasing numbers of preterm infants 1 and ever-improving potentials
      in neonatal medicine will lead to a rising incidence in infantile feeding
      problems. Profound knowledge regarding the development and anatomy of pre- and
      postnatal swallowing functions is essential for the assessment and therapy of
      infantile feeding and swallowing problems. METHOD: For this systematic review a
      selective literature research in PubMed has been carried out. RESULTS:
      Oropharyngeal structures and oral-motor skills for sucking and swallowing develop
      during embryonic and foetal stages and enable postnatal oral feeding. Knowledge
      of pre- and postnatal developmental stages of oral-motor development and
      swallowing serves as a base for the assessment of preterm infants' abilities and
      tolerance for feeding. A direct comparison of the swallowing process between
      infants, children and adults is not possible due to different anatomical
      characteristics. Developmental processes and neurologically triggered
      coordination procedures of early feeding skills are complex and very susceptible
      to faults. Disruption can cause severe disorders of swallowing coordination.
      Feeding problems are a common problem in preterm infants. Differentiated
      assessments on the basis of these results and early intervention facilitating
      oral-motor skills can accelerate the transition from tube to oral feeding and
      prevent further feeding issues.

PMID- 24683160
TI  - [Explosive trauma in the buccal cavity].

PMID- 24683161
TI  - [Cave! Liability for inadequate safety information at discharge from inpatient
      care against medical advice].

PMID- 24683162
TI  - [Differential diagnosis of hoarseness].
AB  - Hoarseness can be the leading symptom of dysphonia. In combination with impaired
      vocal performance and subjective voice-related discomfort, it can represent an
      individually different handicap for patients and lead to limited participation in
      social and professional life. Since the reasons for dysphonia may be not only
      functional but also organic with a potentially poor prognosis, hoarseness must be
      clarified using differential diagnosis. In addition to the knowledge of possible
      diseases, pathogenesis, and treatment options for dysphonia, the differential
      diagnostic approach requires profound knowledge of the various diagnostic
      methods, and of the interpretation of the results in particular. The etiology of
      dysphonia is very diverse and rarely monocausal. Therefore, a team-based and
      interdisciplinary differential diagnostic approach is recommended. 

PMID- 24683163
TI  - [Operation methods: safe, logical and step by step fronto-ethmoidectomy with or
      without type 1, 2, 3 frontal sinusotomy - 1].

PMID- 24683164
TI  - Analysis of volatile components extracted from the peels of four different
      Chinese pomelos using TDS-GC-MS.
AB  - BACKGROUND: The rational utilization of the resources of Chinese pomelo peels
      requires reliable fast evaluation methods for their quality. However, how to
      improve the accuracy of prediction of the volatile organic compounds in the peels
      is not well addressed. In this study dynamic headspace collection combined with
      thermal desorption system/cold trap injection and gas chromatography-mass
      spectrometry (TDS-GC-MS) was employed to examine the volatile organic compounds
      in the peels of four different types of Chinese pomelos. RESULTS: All four kinds
      of pomelo peels contained substantial quantities of olefins, such as limonene,
      beta-myrcene, alpha-pinene, beta-pinene, alpha-phellandrene and terpinolene,
      although there were obvious differences in the volatile organic compound profiles
      obtained from the pomelos under the same test conditions. Extractions of Yuhuan,
      Xiangyou, Huangjin sweet and Guanxi sweet pomelo peels were found in a total of
      34, 16, 9 and 20 different volatile compounds, representing total mass fractions
      of 99.18%, 99.88%, 100% and 99.33% of the overall extraction yield. CONCLUSION:
      The advantage of this innovative method to the determination of volatile
      components in the peels of different pomelos is that it allows volatile
      components to be extracted from the fruit in its natural state. The volatile
      organic compounds of different kinds of pomelo peels under the same test
      conditions were obviously different. The results obtained in this study
      demonstrate that this method represents a novel and rapid means of evaluating
      pomelo peel quality.

PMID- 24683165
TI  - High-quality three-dimensional nanoporous graphene.
AB  - We report three-dimensional (3D) nanoporous graphene with preserved 2D electronic
      properties, tunable pore sizes, and high electron mobility for electronic
      applications. The complex 3D network comprised of interconnected graphene retains
      a 2D coherent electron system of massless Dirac fermions. The transport
      properties of the nanoporous graphene show a semiconducting behavior and strong
      pore-size dependence, together with unique angular independence. The free
      standing, large-scale nanoporous graphene with 2D electronic properties and high
      electron mobility holds great promise for practical applications in 3D electronic
      devices. 

PMID- 24683166
TI  - [Claus Claussen -- a pioneer of modern radiology].

PMID- 24683167
TI  - Endovascular aneurysm repair of abdominal aortic aneurysms: standards, technical
      options and advanced indications.
AB  - Since the introduction of endovascular aneurysm repair (EVAR) in 1991, the
      endovascular therapy with newest stent grafts has assumed a prominent role in the
      clinical management of abdominal aortic aneurysms (AAA) with a superior
      perioperative mortality of EVAR and an equivalent mid-term outcome, compared to
      open surgery. Newest techniques using chimney or periscope grafts and customized
      fenestrated and branched stent grafts allow the endovascular treatment of complex
      pararenal AAA. This article reviews EVAR in the treatment of AAA, evidence based
      results and advanced indication by newest interventional techniques and technical
      developments. KEY POINTS: * EVAR has become standard treatment of abdominal
      aortic aneurysm with equivalent results to open surgery.* Technical advancements
      and the introduction of newest stent grafts continually expand the indication of
      EVAR.* Chimney- and periscope grafts as well as custom-made prothesis systems
      allow endovascular treatment of complex para- and suprarenal aneurysms.

PMID- 24683168
TI  - Assessment of relapse in patients with peritoneal carcinomatosis after
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using F-18
      FDG-PET/CT.
AB  - PURPOSE: In patients with peritoneal carcinomatosis (PC), cytoreductive surgery
      combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an evolving
      therapeutic approach with curative intention. The differentiation between
      posttherapeutic findings after HIPEC and relapse of PC is challenging. We
      evaluated the diagnostic value of F-18-FDG-PET/CT in patients with relapse of PC
      after HIPEC. MATERIALS AND METHODS: 36 patients with recurring PC after HIPEC
      were examined on a whole-body PET/CT system (44 examinations). The examination
      included 3 D F-18-FDG-PET and contrast-enhanced CT. Images were assessed by two
      experienced readers regarding the presence and the extent of PC using the
      peritoneal carcinomatosis index (PCI). Imaging results were correlated with
      surgical findings or follow-up. RESULTS: Relapse was suspected in 40 of 44
      examinations. Relapse was missed by F-18-FDG PET/CT in 4 patients and
      significantly underestimated in 8 patients. The diagnostic accuracy for the
      detection of PC on a patient basis was 91 %, the sensitivity was 91 % and the
      positive predictive value was 100 %. The mean PCI was 11.4 +/- 11.9 for PET/CT,
      8.4 +/- 10.3 for CT and 16.6 +/- 15.0 in the case of surgical exploration. The
      extent of PC was underestimated by PET/CT and even more by CT alone (p < 0.05).
      CONCLUSION: The diagnostic value of F-18-FDG PET/CT after cytoreductive surgery
      and HIPEC in the detection of recurring PC is superior to contrast-enhanced CT.
      However, the quantification of the extent of PC is limited due to post
      therapeutic tissue alterations. KEY POINTS: * Imaging of recurrent PC after HIPEC
      is challenging due to posttherapeutic tissue alterations.* The extent of
      recurrent PC after HIPEC is systematically underestimated by F-18-FDG PET/CT.* F
      18-FDG PET/CT provides improved sensitivity for recurrent PC compared to contrast
      enhanced CT.* The correlation of the extent of recurrent PC depicted by F-18-FDG
      PET/CT and surgical exploration is better than that of contrast-enhanced CT and
      surgical exploration.

PMID- 24683169
TI  - Magnetic resonance imaging of single co-labeled mesenchymal stromal cells after
      intracardial injection in mice.
AB  - PURPOSE: The aim of this study was to establish co-labeling of mesenchymal
      stromal cells (MSC) for the detection of single MSC in-vivo by MRI and
      histological validation. MATERIALS AND METHODS: Mouse MSC were co-labeled with
      fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester
      (CFSE). The cellular iron content was determined by atomic absorption
      spectrometry. Cell proliferation and expression of characteristic surface markers
      were determined by flow cytometry. The chondrogenic differentiation capacity was
      assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were
      injected into the left heart ventricle of 12 mice. The animals underwent
      sequential MRI on a clinical 3.0 T scanner (Intera, Philips Medical Systems,
      Best, The Netherlands). For histological validation cryosections were examined by
      fluorescent microscopy. RESULTS: Magnetic and fluorescent labeling of MSC was
      established (mean cellular iron content 23.6 +/- 3 pg). Flow cytometry showed
      similar cell proliferation and receptor expression of labeled and unlabeled MSC.
      Chondrogenic differentiation of labeled MSC was verified. After cell injection
      MRI revealed multiple signal voids in the brain and fewer signal voids in the
      kidneys. In the brain, an average of 4.6 +/- 1.2 (n1), 9.0 +/- 3.6 (n2) and 25.0
      +/- 1.0 (n3) signal voids were detected per MRI slice. An average of 8.7 +/- 3.1
      (n1), 22.0 +/- 6.1 (n2) and 89.8 +/- 6.5 (n3) labeled cells per corresponding
      stack of adjacent cryosections could be detected in the brain. Statistical
      correlation of the numbers of MRI signal voids in the brain and single MSC found
      by histology revealed a correlation coefficient of r = 0.91. CONCLUSION: The
      study demonstrates efficient magnetic and fluorescent co-labeling of MSC and
      their detection on a single cell level in mice by in-vivo MRI and histology. The
      described techniques may broaden the methods for in-vivo tracking of MSC. KEY
      POINTS: * Detection of single magnetically labeled MSC in-vivo using a clinical
      3.0 T MRI is possible.* Fluorescent and magnetic co-labeling does not affect cell
      vitality.* The number of cells detected by MRI and histology has a high
      correlation.

PMID- 24683170
TI  - Establishment of functional and molecular ultrasound for breast cancer xenograft
      imaging.
AB  - The present work was originally published in European Radiology and as a PhD
      thesis at the RWTH Aachen University and was conducted at the Institute for
      Experimental Molecular Imaging at the RWTH Aachen University.

PMID- 24683171
TI  - [In memoriam Univ.-Prof. Dr. med. Dipl. Chem. Werner A. Kaiser].

PMID- 24683172
TI  - High degree of polymerization in a fullerene-containing supramolecular polymer.
AB  - Supramolecular polymers based on dispersion forces typically show lower molecular
      weights (MW) than those based on hydrogen bonding or metal-ligand coordination.
      We present the synthesis and self-assembling properties of a monomer featuring
      two complementary units, a C60 derivative and an exTTF-based macrocycle, that
      interact mainly through pi-pi, charge-transfer, and van der Waals interactions.
      Thanks to the preorganization in the host part, a remarkable log K(a)=5.1+/-0.5
      in CHCl3 at room temperature is determined for the host-guest couple. In
      accordance with the large binding constant, the monomer self-assembles in the gas
      phase, in solution, and in the solid state to form linear supramolecular polymers
      with a very high degree of polymerization. A MW above 150 kDa has been found
      experimentally in solution, while in the solid state the monomer forms
      extraordinarily long, straight, and uniform fibers with lengths reaching several
      microns.

PMID- 24683174
TI  - Phosphate monoester hydrolysis by trinuclear alkaline phosphatase; DFT study of
      transition States and reaction mechanism.
AB  - Alkaline phosphatase (AP) is a trinuclear metalloenzyme that catalyzes the
      hydrolysis of a broad range of phosphate monoesters to form inorganic phosphate
      and alcohol (or phenol). In this paper, by using density functional theory with a
      model based on a crystal structure, the AP-catalyzed hydrolysis of phosphate
      monoesters is investigated by calculating two substrates, that is, methyl and p
      nitrophenyl phosphates, which represent alkyl and aryl phosphates, respectively.
      The calculations confirm that the AP reaction employs a "ping-pong" mechanism
      involving two chemical displacement steps, that is, the displacement of the
      substrate leaving group by a Ser102 alkoxide and the hydrolysis of the
      phosphoseryl intermediate by a Zn2-bound hydroxide. Both displacement steps
      proceed via a concerted associative pathway no matter which substrate is used.
      Other mechanistic aspects are also studied. Comparison of our calculations with
      linear free energy relationships experiments shows good agreement. 

PMID- 24683177
TI  - Global educational disparities in the associations between body mass index and
      diabetes mellitus in 49 low-income and middle-income countries.
AB  - BACKGROUND: Despite the well-established link between body mass index (BMI) and
      diabetes mellitus (DM), it remains unclear whether this association is more
      pronounced at certain levels of education. This study assessed the modifying
      effect of educational attainment on the associations between BMI and DM-as well
      as the joint associations of BMI and education with DM-in low-income countries
      (LICs) and middle-income countries (MICs). METHODS: The authors used cross
      sectional data from 160 381 participants among 49 LICs and MICs in the World
      Health Survey. Overweight and obesity levels were defined using WHO's
      classification. Educational attainment was classified in four categories: 'no
      formal education', 'some/completed primary school', 'secondary/high school
      completed' and 'college and beyond'. We used random-intercept multilevel logistic
      regressions to investigate the modifying influence of educational attainment on
      the associations of different BMI levels-as well as their joint associations-with
      DM. RESULTS: We found positive associations between excessive BMI and DM at each
      education level in both LICs and MICs. We found that the joint associations of
      BMI and education with DM were larger than the product of their separate single
      associations among females in LICs. With joint increases in BMI and education,
      males and females in LICs had similar increased odds of DM, but males had higher
      such odds than females in MICs. CONCLUSIONS: BMI and education are associated
      with the DM, but the associations seem to differ in complex ways between LICs and
      MICs and by gender.

PMID- 24683176
TI  - J-shapedness: an often missed, often miscalculated relation: the example of
      weight and mortality.
AB  - We present three considerations in analysing the association between weight and
      mortality, as well as other relations that might be non-linear in nature. First,
      authors must graphically plot their independent and dependent variables in a
      continuous manner. Second, authors should assess the shape of that relation, and
      note its shape. If it is non-linear, and specifically, J-shaped or U-shaped,
      careful consideration should be given to using the 'best' statistical model, of
      which multivariate fractional polynomial regression is a reasonable choice.
      Authors should also refrain from truncating their data to avoid dealing with non
      linear relations. 

PMID- 24683178
TI  - Has the economic crisis widened the intraurban socioeconomic inequalities in
      mortality? The case of Barcelona, Spain.
AB  - BACKGROUND: There is considerable evidence demonstrating socioeconomic
      inequalities in mortality, some of which focuses on intraurban inequalities.
      However, all the studies assume that the spatial variation of inequalities is
      stable over the time. We challenge this assumption and propose two hypotheses:
      (i) have spatial variations in socioeconomic inequalities in mortality at an
      intraurban level changed over time? and (ii) as a result of the economic crisis,
      has the gap between such disparities widened? In this paper, our objective is to
      assess the effect of the economic recession on the spatio-temporal variation of
      socioeconomic inequalities in mortality in Barcelona (Catalonia, Spain). METHODS:
      We used a spatio-temporal ecological design to analyse mortality inequalities at
      small area level in Barcelona. Mortality data and socioeconomic indicators
      correspond to the years 2005 and 2008-2011. We specified spatio-temporal
      ecological mixed regressions for both men and women using two indicators,
      neighbourhood and year. We allowed the coefficients of the socioeconomic
      variables to differ according to the levels and explicitly took into account
      spatio-temporal adjustment. RESULTS: For men and women both absolute and, above
      all, relative risks for mortality have increased since 2009. In relative terms,
      this means that the risk of dying has increased much more in the most
      economically deprived neighbourhoods than in the more affluent ones. CONCLUSIONS:
      Although the geographical pattern in relative risks for mortality in
      neighbourhoods in Barcelona remained very stable between 2005 and 2011,
      socioeconomic inequalities in mortality at an intraurban level have surged since
      2009.

PMID- 24683179
TI  - A modified technique of Konno aortoventriculoplasty for redo aortic valve
      replacement procedures.
AB  - This article puts forward a modified technique of Konno aortoventriculoplasty for
      repeat procedures. After incision of the ventricular septum, this approach
      involves aortic valve replacement using a mechanical valved conduit,
      reimplantation of the coronary arteries, and graft replacement of the ascending
      aorta. This modification allows the removal of the diseased ascending aortic wall
      caused by a previous patch enlargement or poststenotic dilation. 

PMID- 24683180
TI  - Photo-oxidative stress markers as a measure of abiotic stress-induced leaf
      senescence: advantages and limitations.
AB  - Inside chloroplasts, several abiotic stresses (including drought, high light,
      salinity, or extreme temperatures) induce a reduction in CO2 assimilation rates
      with a consequent increase in reactive oxygen species (ROS) production,
      ultimately leading to leaf senescence and yield loss. Photo-oxidation processes
      should therefore be mitigated to prevent leaf senescence, and plants have evolved
      several mechanisms to either prevent the formation of ROS or eliminate them.
      Technology evolution during the past decade has brought faster and more precise
      methodologies to quantify ROS production effects and damage, and the capacities
      of plants to withstand oxidative stress. Nevertheless, it is very difficult to
      disentangle photo-oxidative processes that bring leaf defence and acclimation,
      from those leading to leaf senescence (and consequently death). It is important
      to avoid the mistake of discussing results on leaf extracts as being equivalent
      to chloroplast extracts without taking into account that other organelles, such
      as peroxisomes, mitochondria, or the apoplast also significantly contribute to
      the overall ROS production within the cell. Another important aspect is that
      studies on abiotic stress-induced leaf senescence in crops do not always include
      a time-course evolution of studied processes, which limits our knowledge about
      what photo-oxidative stress processes are required to irreversibly induce the
      senescence programme. This review will summarize the current technologies used to
      evaluate the extent of photo-oxidative stress in plants, and discuss their
      advantages and limitations in characterizing abiotic stress-induced leaf
      senescence in crops. 

PMID- 24683182
TI  - Epigenetic control of plant senescence and linked processes.
AB  - Senescence processes are part of the plant developmental programme. They involve
      reprogramming of gene expression and are under the control of a complex
      regulatory network closely linked to other developmental and stress-responsive
      pathways. Recent evidence indicates that leaf senescence is regulated via
      epigenetic mechanisms. In the present review, the epigenetic control of plant
      senescence is discussed in the broader context of environment-sensitive plant
      development. The review outlines the concept of epigenetic control of
      interconnected regulatory pathways steering stress responses and plant
      development. Besides giving an overview of techniques used in the field, it
      summarizes recent findings on global alterations in chromatin structure, histone
      and DNA modifications, and ATP-dependent chromatin remodelling during plant
      senescence and linked processes. 

PMID- 24683181
TI  - Transcriptome analysis of an mvp mutant reveals important changes in global gene
      expression and a role for methyl jasmonate in vernalization and flowering in
      wheat.
AB  - The einkorn wheat mutant mvp-1 (maintained vegetative phase 1) has a non
      flowering phenotype caused by deletions including, but not limited to, the genes
      CYS, PHYC, and VRN1. However, the impact of these deletions on global gene
      expression is still unknown. Transcriptome analysis showed that these deletions
      caused the upregulation of several pathogenesis-related (PR) and jasmonate
      responsive genes. These results suggest that jasmonates may be involved in
      flowering and vernalization in wheat. To test this hypothesis, jasmonic acid (JA)
      and methyl jasmonate (MeJA) content in mvp and wild-type plants was measured. The
      content of JA was comparable in all plants, whereas the content of MeJA was
      higher by more than 6-fold in mvp plants. The accumulation of MeJA was also
      observed in vernalization-sensitive hexaploid winter wheat during cold exposure.
      This accumulation declined rapidly once plants were deacclimated under floral
      inductive growth conditions. This suggests that MeJA may have a role in floral
      transition. To confirm this result, we treated vernalization-insensitive spring
      wheat with MeJA. The treatment delayed flowering with significant downregulation
      of both TaVRN1 and TaFT1 genes. These data suggest a role for MeJA in modulating
      vernalization and flowering time in wheat. 

PMID- 24683183
TI  - Phenol homeostasis is ensured in vanilla fruit by storage under solid form in a
      new chloroplast-derived organelle, the phenyloplast.
AB  - A multiple cell imaging approach combining immunofluorescence by confocal
      microscopy, fluorescence spectral analysis by multiphotonic microscopy, and
      transmission electron microscopy identified the site of accumulation of 4-O-(3
      methoxybenzaldehyde) beta-d-glucoside, a phenol glucoside massively stockpiled by
      vanilla fruit. The glucoside is sufficiently abundant to be detected by spectral
      analysis of its autofluorescence. The convergent results obtained by these
      different techniques demonstrated that the phenol glucoside accumulates in the
      inner volume of redifferentiating chloroplasts as solid amorphous deposits, thus
      ensuring phenylglucoside cell homeostasis. Redifferentiation starts with the
      generation of loculi between thylakoid membranes which are progressively filled
      with the glucoside until a fully matured organelle is obtained. This peculiar
      mode of storage of a phenolic secondary metabolite is suspected to occur in other
      plants and its generalization in the Plantae could be considered. This new
      chloroplast-derived organelle is referred to as a 'phenyloplast'. 

PMID- 24683184
TI  - Defining the Role of prolamin-box binding factor1 Gene During Maize
      Domestication.
AB  - The prolamin-box binding factor1 (pbf1) gene encodes a transcription factor that
      controls the expression of seed storage protein (zein) genes in maize. Prior
      studies show that pbf1 underwent selection during maize domestication although
      how it affected trait change during domestication is unknown. To assay how pbf1
      affects phenotypic differences between maize and teosinte, we compared nearly
      isogenic lines (NILs) that differ for a maize versus teosinte allele of pbf1
      Kernel weight for the teosinte NIL (162mg) is slightly but significantly greater
      than that for the maize NIL (156mg). RNAseq data for developing kernels show that
      the teosinte allele of pbf1 is expressed at about twice the level of the maize
      allele. However, RNA and protein assays showed no difference in zein profile
      between the two NILs. The lower expression for the maize pbf1 allele suggests
      that selection may have favored this change; however, how reduced pbf1 expression
      alters phenotype remains unknown. One possibility is that pbf1 regulates genes
      other than zeins and thereby is a domestication trait. The observed drop in seed
      weight associated with the maize allele of pbf1 is counterintuitive but could
      represent a negative pleiotropic effect of selection on some other aspect of
      kernel composition.

PMID- 24683185
TI  - HLA-DRalpha1 constructs block CD74 expression and MIF effects in experimental
      autoimmune encephalomyelitis.
AB  - CD74, the cell-surface form of the MHC class II invariant chain, is a key
      inflammatory factor that is involved in various immune-mediated diseases as part
      of the macrophage migration inhibitory factor (MIF) binding complex. However,
      little is known about the natural regulators of CD74 in this context. In order to
      study the role of the HLA-DR molecule in regulating CD74, we used the HLA
      DRalpha1 domain, which was shown to bind to and downregulate CD74 on CD11b(+)
      monocytes. We found that DRalpha1 directly inhibited binding of MIF to CD74 and
      blocked its downstream inflammatory effects in the spinal cord of mice with
      experimental autoimmune encephalomyelitis (EAE). Potency of the DRalpha1 domain
      could be destroyed by trypsin digestion but enhanced by addition of a peptide
      extension (myelin oligodendrocyte glycoprotein [MOG]-35-55 peptide) that provided
      secondary structure not present in DRalpha1. These data suggest a
      conformationally sensitive determinant on DRalpha1-MOG that is responsible for
      optimal binding to CD74 and antagonism of MIF effects, resulting in reduced
      axonal damage and reversal of ongoing clinical and histological signs of EAE.
      These results demonstrate natural antagonist activity of DRalpha1 for MIF that
      was strongly potentiated by the MOG peptide extension, resulting in a novel
      therapeutic, DRalpha1-MOG-35-55, that within the limitations of the EAE model may
      have the potential to treat autoimmune diseases such as multiple sclerosis. 

PMID- 24683186
TI  - Cell depletion in mice that express diphtheria toxin receptor under the control
      of SiglecH encompasses more than plasmacytoid dendritic cells.
AB  - Plasmacytoid dendritic cells (pDC) produce IFN-I in response to viruses and are
      routinely identified in mice by SiglecH expression. SiglecH is a sialic acid
      binding Ig-like lectin that has an immunomodulatory role during viral infections.
      In this study, we evaluated the impact of SiglecH deficiency on cytokine
      responses in the presence and absence of pDC. We found that lack of SiglecH
      enhanced IFN-I responses to viral infection, regardless of whether pDC were
      depleted. We also examined the expression pattern of SiglecH and observed that it
      was expressed by specialized macrophages and progenitors of classical dendritic
      cells and pDC. Accordingly, marginal zone macrophages and pDC precursors were
      eliminated in newly generated SiglecH-diphtheria toxin receptor (DTR)-transgenic
      (Tg) mice but not in CLEC4C-DTR-Tg mice after diphtheria toxin (DT) treatment.
      Using two bacterial models, we found that SiglecH-DTR-Tg mice injected with DT
      had altered bacterial uptake and were more susceptible to lethal Listeria
      monocytogenes infection than were DT-treated CLEC4C-DTR-Tg mice. Taken together,
      our findings suggest that lack of SiglecH may affect cytokine responses by cell
      types other than pDC during viral infections, perhaps by altering viral
      distribution or burden, and that cell depletion in SiglecH-DTR-Tg mice
      encompasses more than pDC. 

PMID- 24683187
TI  - Contrasted innate responses to two viruses in zebrafish: insights into the
      ancestral repertoire of vertebrate IFN-stimulated genes.
AB  - Ease of imaging and abundance of genetic tools make the zebrafish an attractive
      model host to understand host-pathogen interactions. However, basic knowledge
      regarding the identity of genes involved in antiviral immune responses is still
      lagging in this species. We conducted a microarray analysis of the larval
      zebrafish response to two models of RNA virus infections with very different
      outcomes. Chikungunya virus (CHIKV) induces a rapid and protective IFN response.
      Infection with infectious hematopoietic necrosis virus is lethal and is
      associated with a delayed and inefficient IFN response. A typical signature of
      IFN-stimulated genes (ISGs) was observed with both viruses, but was stronger for
      CHIKV. We further compared the zebrafish and human ISG repertoires and made a
      genomic and phylogenic characterization of the main gene families. We describe a
      core set of well-induced ISGs conserved across vertebrates, as well as multigenic
      families diversified independently in each taxon. The conservation of ISGs
      involved in antiviral signaling indicates conservation of the main feedback loops
      in these pathways. Whole-mount in situ hybridization of selected transcripts in
      infected larvae revealed a typical pattern of expression for ISGs in the liver,
      gut, and blood vessels with both viruses. We further show that some inflammatory
      genes were additionally induced through IFN-independent pathways by infectious
      hematopoietic necrosis virus and not by CHIKV. This study provides a useful
      reference set for the analysis of host-virus interactions in zebrafish and
      highlights the differences between protective and nonprotective antiviral innate
      responses. 

PMID- 24683188
TI  - Molecular mechanisms of TLR2-mediated antigen cross-presentation in dendritic
      cells.
AB  - Cross-presentation is a key function of dendritic cells (DCs), which present
      exogenous Ags on MHC class I molecules to prime CTL responses. The effects of TLR
      triggering on the cross-presentation of exogenous Ags by DCs remain unclear. In
      this study, we used synthetic dipalmitoylated peptides and TLR2 agonist
      conjugated peptides as models to elucidate the mechanisms of TLR2-mediated cross
      presentation. We observed that the internalization of dipalmitoylated peptides by
      bone marrow-derived DCs was facilitated by TLR2 via clathrin-mediated
      endocytosis. The administration of these dipalmitoylated peptide-pulsed bone
      marrow-derived DCs eliminated established tumors through TLR2 signaling. We
      further demonstrated that the induction of Ag-specific CTL responses and tumor
      regression by dipalmitoylated peptides was TAP independent. In addition,
      presentation of dipalmitoylated peptides by MHC class I molecules was blocked in
      the presence of an endosomal acidification inhibitor (chloroquine) or a lysosomal
      degradation inhibitor (Z-FL-COCHO). The endocytosed dipalmitoylated peptide also
      passed rapidly from early endosome Ag-1-positive endosomes to RAS-related GTP
      binding protein 7 (Rab7)-associated late endosomes compared with their
      nonlipidated counterparts. Furthermore, we found that dipalmitoylated peptide
      upregulated Rab7 expression correlated with Ag presentation via the TLR2/MyD88
      pathway. Both JNK and ERK signaling pathways are required for upregulation of
      Rab7. In summary, our data suggest that TLR2-mediated cross-presentation occurs
      through the upregulation of Rab7 and a TAP-independent pathway that prime CTL
      responses. 

PMID- 24683189
TI  - Altered expression of oligodendrocyte and neuronal marker genes predicts the
      clinical onset of autoimmune encephalomyelitis and indicates the effectiveness of
      multiple sclerosis-directed therapeutics.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a valuable model for studying
      immunopathology in multiple sclerosis (MS) and for exploring the interface
      between autoimmune responses and CNS tissue that ultimately leads to lesion
      development. In this study, we measured gene expression in mouse spinal cord
      during myelin oligodendrocyte gp35-55 peptide-induced EAE, using quantitative RT
      PCR, to identify gene markers that monitor individual hallmark pathological
      processes. We defined a small panel of genes whose longitudinal expression
      patterns provided insight into the timing, interrelationships, and mechanisms of
      individual disease processes and the efficacy of therapeutics for the treatment
      of MS. Earliest transcriptional changes were upregulation of Il17a and sharp
      downregulation of neuronal and oligodendrocyte marker genes preceding clinical
      disease onset, whereas neuroinflammatory markers progressively increased as
      symptoms and tissue lesions developed. EAE-induced gene-expression changes were
      not altered in mice deficient in IKKbeta in cells of the myeloid lineage compared
      with controls, but the administration of a selective inhibitor of soluble TNF to
      mice from the day of immunization delayed changes in the expression of innate
      inflammation, myelin, and neuron markers from the presymptomatic phase. Proof of
      principle that the gene panel shows drug screening potential was obtained using a
      well-established MS therapeutic, glatiramer acetate. Prophylactic treatment of
      mice with glatiramer acetate normalized gene marker expression, and this
      correlated with the level of therapeutic success. These results show that neurons
      and oligodendrocytes are highly sensitive to CNS-directed autoimmunity before the
      development of clinical symptoms and immunopathology and reveal a role for
      soluble TNF in mediating the earliest changes in gene expression. 

PMID- 24683190
TI  - Periodontal pathogens directly promote autoimmune experimental arthritis by
      inducing a TLR2- and IL-1-driven Th17 response.
AB  - Increasing epidemiologic evidence supports a link between periodontitis and
      rheumatoid arthritis. The actual involvement of periodontitis in the pathogenesis
      of rheumatoid arthritis and the underlying mechanisms remain, however, poorly
      understood. We investigated the influence of concomitant periodontitis on
      clinical and histopathologic characteristics of T cell-mediated experimental
      arthritis and evaluated modulation of type II collagen (CII)-reactive Th cell
      phenotype as a potential mechanism. Repeated oral inoculations of periodontal
      pathogens Porphyromonas gingivalis and Prevotella nigrescens induced
      periodontitis in mice, as evidenced by alveolar bone resorption. Interestingly,
      concurrent periodontitis induced by both bacteria significantly aggravated the
      severity of collagen-induced arthritis. Exacerbation of arthritis was
      characterized by increased arthritic bone erosion, whereas cartilage damage
      remained unaffected. Both P. gingivalis and P. nigrescens skewed the CII-specific
      T cell response in lymph nodes draining arthritic joints toward the Th17
      phenotype without affecting Th1. Importantly, the levels of IL-17 induced by
      periodontal pathogens in CII-specific T cells directly correlated with the
      intensity of arthritic bone erosion, suggesting relevance in pathology.
      Furthermore, IL-17 production was significantly correlated with periodontal
      disease-induced IL-6 in lymph node cell cultures. The effects of the two bacteria
      diverged in that P. nigrescens, in contrast to P. gingivalis, suppressed the
      joint-protective type 2 cytokines, including IL-4. Further in vitro studies
      showed that the Th17 induction strongly depended on TLR2 expression on APCs and
      was highly promoted by IL-1. Our data provide evidence of the involvement of
      periodontitis in the pathogenesis of T cell-driven arthritis through induction of
      Ag-specific Th17 response. 

PMID- 24683192
TI  - NKT cells determine titer and subtype profile of virus-specific IgG antibodies
      during herpes simplex virus Infection.
AB  - Invariant NKT cells (iNKT cells) are innate lymphocytes that recognize lipid
      derived Ags presented by the MHC class I-related protein CD1d. In this study, we
      analyzed the role of iNKT cells in the generation of Abs against HSV type 1 (HSV
      1). In sera from healthy hman donors, we found a correlation between HSV-1
      specific IgG titers and proportions of CD4(+) iNKT cells. In HSV-1-infected iNKT
      cell-deficient mice, the amount of specific IgM and IgG Abs were significantly
      reduced compared with wild-type mice. Moreover, iNKT cell-deficient mice were
      unable to upregulate CD1d on B cells and failed to establish an IFN-gamma-driven
      subtype profile of HSV-1-specific IgG Abs. In spleens of HSV-1-infected wild-type
      mice, the percentage of iNKT cells expressing CCR6, a marker for inflammatory
      iNKT cells secreting IFN-gamma, was significantly decreased at 6 mo
      postinfection, suggesting that these cells were released from the spleen to other
      tissues. Finally, in vitro experiments showed that in the absence of CD1d
      restricted cells, HSV-1 induced markedly lower IFN-gamma production in
      splenocytes from naive mice. Taken together, our results indicate that iNKT cells
      shape the Ab response to HSV-1 infection and provide a basis for rational
      development of antiviral vaccines. 

PMID- 24683191
TI  - Mechanistic target of rapamycin complex 1 expands Th17 and IL-4+ CD4-CD8- double
      negative T cells and contracts regulatory T cells in systemic lupus
      erythematosus.
AB  - The mechanistic target of rapamycin (mTOR) is activated in CD4(-)CD8(-) double
      negative (DN) T cells and its blockade is therapeutic in systemic lupus
      erythematosus (SLE) patients. Murine studies showed the involvement of mTOR
      complex 1 (mTORC1) and 2 (mTORC2) in the differentiation of Th1/Th17 cells and
      Th2 cells, respectively. In this study, we investigated the roles of mTORC1 and
      mTORC2 in T cell lineage development in SLE and matched healthy control (HC)
      subjects. mTORC1 activity was increased, whereas mTORC2 was reduced, as assessed
      by phosphorylation of their substrates phosphorylated S6 kinase 1 or
      phosphorylated S6 ribosomal protein and phosphorylated Akt, respectively.
      Rapamycin inhibited mTORC1 and enhanced mTORC2. IL-4 expression was increased in
      freshly isolated CD8(+) lupus T cells (SLE: 8.09 +/- 1.93%, HC: 3.61 +/- 0.49%; p
      = 0.01). DN T cells had greater IL-4 expression than CD4(+) or CD8(+) T cells of
      SLE patients after 3-d in vitro stimulation, which was suppressed by rapamycin
      (control: 9.26 +/- 1.48%, rapamycin: 5.03 +/- 0.66%; p < 0.001). GATA-3
      expression was increased in CD8(+) lupus T cells (p < 0.01) and was insensitive
      to rapamycin treatment. IFN-gamma expression was reduced in all lupus T cell
      subsets (p = 1.0 * 10(-5)) and also resisted rapamycin. IL-17 expression was
      increased in CD4(+) lupus T cells (SLE: 3.62 +/- 0.66%, HC: 2.29 +/- 0.27%; p =
      0.019), which was suppressed by rapamycin (control: 3.91 +/- 0.79%, rapamycin:
      2.22 +/- 0.60%; p < 0.001). Frequency of regulatory T cells (Tregs) was reduced
      in SLE (SLE: 1.83 +/- 0.25%, HC: 2.97 +/- 0.27%; p = 0.0012). Rapamycin inhibited
      mTORC1 in Tregs and promoted their expansion. Neutralization of IL-17, but not IL
      4, also expanded Tregs in SLE and HC subjects. These results indicate that mTORC1
      expands IL-4(+) DN T and Th17 cells, and contracts Tregs in SLE. 

PMID- 24683193
TI  - Heterocomplex formation between MBL/ficolin/CL-11-associated serine protease-1
      and -3 and MBL/ficolin/CL-11-associated protein-1.
AB  - The activity of the complement system is tightly controlled by many fluid-phase
      and tissue-bound regulators. Mannose-binding lectin (MBL)/ficolin/collectin-11
      associated protein-1 (MAP-1) is a recently discovered plasma protein that acts as
      an upstream inhibitor of the lectin complement pathway (LCP). It has previously
      been shown that MAP-1 can compete with the MBL/ficolin/collectin-11-associated
      serine proteases (MASPs) in binding to MBL and the ficolins. However, this
      mechanism may only partly explain the inhibitory complement effect of MAP-1. We
      hypothesized that MAP-1 is also involved in heterocomplex formation with the
      MASPs thereby breaking the stoichiometry of the activation complexes of the LCP,
      which could represent an alternative mechanism of MAP-1-mediated complement
      inhibition. We assessed the heterocomplex formation with ELISA, size-exclusion
      chromatography, and immunoblotting using both recombinant proteins and
      serum/plasma. We found that rMAP-1 can engage in heterocomplexes with rMASP-1 and
      rMASP-3 in a calcium-dependent manner. Moreover, we discovered that rMASP-1 and
      rMASP-3 also form heterocomplexes under these conditions. Complexes containing
      both MAP-1 and MASP-1 or -3 were detected in normal human serum and plasma, and
      depletion of the LCP recognition molecules from ficolin-3-deficient human serum
      showed that free circulating heterocomplexes also exist in the blood, although
      the major part appears to be associated with the LCP recognition molecules.
      Altogether, these findings suggest that MASPs can associate in various
      combinations and bring new perspectives to the complexity of lectin pathway
      driven complement activation. 

PMID- 24683194
TI  - TCR bias and affinity define two compartments of the CD1b-glycolipid-specific T
      Cell repertoire.
AB  - Current views emphasize TCR diversity as a key feature that differentiates the
      group 1 (CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 systems. Whereas TCR sequence
      motifs define CD1d-reactive NKT cells, the available data do not allow a TCR
      based organization of the group 1 CD1 repertoire. The observed TCR diversity
      might result from donor-to-donor differences in TCR repertoire, as seen for MHC
      restricted T cells. Alternatively, diversity might result from differing CD1
      isoforms, Ags, and methods used to identify TCRs. Using CD1b tetramers to isolate
      clones recognizing the same glycolipid, we identified a previously unknown
      pattern of V gene usage (TRAV17, TRBV4-1) among unrelated human subjects. These
      TCRs are distinct from those present on NKT cells and germline-encoded mycolyl
      lipid-reactive T cells. Instead, they resemble the TCR of LDN5, one of the first
      known CD1b-reactive clones that was previously thought to illustrate the
      diversity of the TCR repertoire. Interdonor TCR conservation was observed in
      vitro and ex vivo, identifying LDN5-like T cells as a distinct T cell type. These
      data support TCR-based organization of the CD1b repertoire, which consists of at
      least two compartments that differ in TCR sequence motifs, affinity, and
      coreceptor expression. 

PMID- 24683195
TI  - A novel multivalent, single-domain antibody targeting TcdA and TcdB prevents
      fulminant Clostridium difficile infection in mice.
AB  - The incidence of Clostridium difficile infection (CDI) and associated mortality
      have increased rapidly worldwide in recent years. Therefore, it is critical to
      develop new therapies for CDI. In this study, we generated a novel, potently
      neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only
      VH (VHH) binding domains against both TcdA and TcdB (designated "ABA") that
      reverses fulminant CDI in mice infected with an epidemic 027 strain after a
      single injection of the antibody. We demonstrated that ABA bound to both toxins
      simultaneously and displayed a significantly enhanced neutralizing activity both
      in vitro and in vivo. Additionally, ABA was able to broadly neutralize toxins
      from clinical C. difficile isolates that express both TcdA and TcdB but failed to
      neutralize the toxin from TcdA(-)TcdB(+) C. difficile strains. This study thus
      provides a rationale for the development of multivalent VHHs that target both
      toxins and are broadly neutralizing for treating severe CDI. 

PMID- 24683196
TI  - Low invasiveness of pneumococcal serotype 11A is linked to ficolin-2 recognition
      of O-acetylated capsule epitopes and lectin complement pathway activation.
AB  - BACKGROUND: The divergent epidemiological behavior of Streptococcus pneumoniae
      serotypes suggests that serotype-specific features such as capsule O-acetylation
      influence the propensity of a strain to cause invasive pneumococcal disease
      (IPD). We hypothesize that innate host factors mediate the observed negative
      association between IPD and the serotype 11A (ST11A) capsule O-acetyltransferase
      gene, wcjE. METHODS: We evaluated the ability of ficolin-2, an initiator of the
      lectin complement pathway that was previously shown to bind ST11A pneumococci, to
      recognize and mediate complement-dependent opsonophagocytosis of different
      pneumococcal serotypes. We supplemented findings with an epidemiological meta
      analysis comparing invasiveness of the 30 most prevalent pneumococcal serotypes.
      RESULTS: Ficolin-2 bound ST11A capsule polysaccharide and other wcjE-containing
      pneumococcal serotypes, except ST9V and ST20B. Ficolin-2 did not bind wcjE-null
      serotypes, including the wcjE-null variant of ST11A, ST11E. We observed C1q
      independent complement deposition and phagocytic killing of pneumococci
      expressing ST11A but not those expressing ST11E. Inhibition of ficolin-2 binding
      abrogated ST11A-associated complement deposition and phagocytosis. In children,
      invasiveness of ST11A was the lowest among serotypes tested in our meta-analysis,
      while ST9V was among the highest. CONCLUSIONS: Ficolin-2 mediates serum
      protection by recognizing specific O-acetylated epitopes of pneumococcal capsule
      polysaccharides, exemplifying a novel host-microbe interaction that innately
      offers serotype-specific immunity to IPD.

PMID- 24683197
TI  - Determinants of prevalent human papillomavirus in recently formed heterosexual
      partnerships: a dyadic-level analysis.
AB  - BACKGROUND: We studied features that predict the presence of human papillomavirus
      (HPV) in a new sexual partnership. METHODS: We analyzed data from the "HPV
      Infection and Transmission Among Couples Through Heterosexual Activity" (HITCH)
      Cohort Study of recently formed partnerships ("dyads"). Women aged 18-24 and
      their male partners were recruited during 2005-2010 in Montreal, Canada. We
      tested genital swabs for detection of 36 HPV types. We defined HPV in a
      partnership as the presence of 1 or more HPV types in either or both partners.
      Using baseline data from 482 dyads, we calculated prevalence ratios to evaluate
      candidate risk factors. RESULTS: Most women (88%) were unvaccinated. Sixty-seven
      percent of dyads harbored HPV. For 49% of dyads, both partners were HPV+. HPV was
      least prevalent in dyads who were in their first vaginal sex relationship (17%)
      and was virtually ubiquitous in dyads for which both partners had concurrent
      partners (96%). Dyads that always used condoms with previous partner(s) were 27%
      (95% confidence interval, 9%-42%) less likely to have HPV. CONCLUSIONS: The
      finding that condom use limited onward spread to future partners is in support of
      condom promotion to prevent sexually transmitted infections. Ongoing monitoring
      of HPV in sexual networks is needed, particularly in populations with suboptimal
      vaccine coverage.

PMID- 24683198
TI  - Diffuse alveolar hemorrhage as a fatal adverse effect of bevacizumab: an autopsy
      case.
AB  - A 71-year-old female with Stage IIIB primary adenocarcinoma was administered a
      three-drug combination therapy consisting of docetaxel, cisplatin and bevacizumab
      as a first-line treatment based on the Phase II clinical trial. On the 32nd day
      after the fourth course of chemotherapy, the patient developed bloody sputum. She
      was found dead at home on the 34th day. Autopsy revealed a diffuse alveolar
      hemorrhage without diffuse alveolar damage. Endothelial cells of the small
      arteries and capillaries were swollen and desquamated, indicating that alveolar
      capillaries were injured. The similar pathological changes in blood vessels were
      also observed in the kidney and the digestive tract. Because diffuse alveolar
      hemorrhage caused by cisplatin and docetaxel has never been reported apart from
      interstitial pneumonitis, bevacizumab is the most suspicious drug for diffuse
      alveolar hemorrhage in our case. Chest physicians and oncologists should be aware
      that although it is very rare, diffuse alveolar hemorrhage can develop during any
      course of chemotherapy with bevacizumab. 

PMID- 24683199
TI  - Two novel gross deletions of TSC2 in Malaysian patients with tuberous sclerosis
      complex and TSC2/PKD1 contiguous deletion syndrome.
AB  - Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder
      affecting multiple organs. Tuberous sclerosis complex is caused by mutation in
      either one of the two disease-causing genes, TSC1 or TSC2, encoding for hamartin
      and tuberin, respectively. TSC2/PKD1 contiguous gene deletion syndrome is a very
      rare condition due to deletion involving both TSC2 and PKD1 genes. Tuberous
      sclerosis complex cannot be easily diagnosed since there is no pathognomonic
      feature, although there are consensus diagnostic criteria for that. Mutation
      analysis is useful and plays important roles. We report here two novel gross
      deletions of TSC2 gene in Malay patients with tuberous sclerosis complex and
      TSC2/PKD1 contiguous gene deletion syndrome, respectively. 

PMID- 24683201
TI  - Elimination of undifferentiated cancer cells by pluripotent stem cell inhibitors.

PMID- 24683200
TI  - Gene therapy for the neurological manifestations in lysosomal storage disorders.
AB  - Over the past several years, considerable progress has been made in the
      development of gene therapy as a therapeutic strategy for a variety of inherited
      metabolic diseases, including neuropathic lysosomal storage disorders (LSDs). The
      premise of gene therapy for this group of diseases is borne of findings that
      genetic modification of a subset of cells can provide a more global benefit by
      virtue of the ability of the secreted lysosomal enzymes to effect cross
      correction of adjacent and distal cells. Preclinical studies in small and large
      animal models of these disorders support the application of either a direct in
      vivo approach using recombinant adeno-associated viral vectors or an ex vivo
      strategy using lentiviral vector-modified hematopoietic stem cells to correct the
      neurological component of these diseases. Early clinical studies utilizing both
      approaches have begun or are in late-stage planning for a small number of
      neuropathic LSDs. Although initial indications from these studies are
      encouraging, it is evident that second-generation vectors that exhibit a greater
      safety profile and transduction activity may be required before this optimism can
      be fully realized. Here, I review recent progress and the remaining challenges to
      treat the neurological aspects of various LSDs using this therapeutic paradigm. 

PMID- 24683203
TI  - Females in the Juvenile Justice System: Who Are They and How Do They Fare?
AB  - Increasing numbers of female youth involved in the juvenile justice system
      highlight the need to examine this population. This study enumerates distinct
      profiles of risk and protection among juvenile court-involved females, examining
      young adult outcomes associated with these profiles. Administrative data on 700
      participants were drawn from multiple service sectors in a Midwest metropolitan
      region. Latent class and Pearson chi-square analyses were used. Five unique
      classes were identified; these classes were associated with young adult outcomes.
      One class of impoverished African American females was most likely to experience
      problematic young adult outcomes but least likely to have received juvenile
      justice services. Findings highlight the heterogeneity in the female juvenile
      court population and discrepancies between service needs and service receipt.

PMID- 24683202
TI  - LC-MS/MS Method for the Simultaneous Determination of Free Urinary Steroids.
AB  - Cortisol homeostasis is implicated in hypertension and metabolic syndrome. Two
      enzymes modulate cortisol availability; 11beta-hydroxysteroid dehydrogenase type
      1 (11beta-HSD1) preferentially converts inactive cortisone to cortisol, whereas
      11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) converts cortisol to
      cortisone. In contrast, 5alpha and 5beta reductases inactivate cortisol by
      conversion to its tetrahydrometabolites: tetrahydrocortisol, allo
      tetrahydrocortisol and tetrahydrocortisone. A subtle local increase in cortisol
      can be detected by measuring 24-h urine metabolites, LC-MS/MS being the reference
      method. The 11beta-HSD2 activity is assessed based on the cortisol/cortisone
      ratio, and the 11beta-HSD1 activity on the (tetrahydrocortisol + allo
      tetrahydrocortisol)/tetrahydrocortisone ratio. To better understand hypertension
      and/or metabolic syndrome pathogenesis a method for simultaneous determination of
      cortisol, cortisone, tetrahydrocortisol, allo-tetrahydrocortisol and
      tetrahydrocortisone was developed and validated in an LC coupled with the new
      detector AB Sciex QTrap(r) 4500 tandem mass spectrometer. The steroids were
      extracted from 1 mL urine, using cortisol-D4 as internal standard. The
      quantification range was 0.1-120 ng/mL for cortisol and cortisone, and 1-120
      ng/mL for tetrahydrometabolites, with >89 % recovery for all analytes. The
      coefficient of variation and accuracy was <10 %, and 85-105 %, respectively. Our
      LC-MS/MS method is accurate and reproducible in accordance with Food and Drug
      Administration guidelines, showing good sensitivity and recovery. This method
      allows the assessment of 11beta-HSD2 and 11beta-HSD1 activities in a single
      analytical run providing an innovative tool to explain etiology of misclassified
      essential hypertension and/or metabolic syndrome.

PMID- 24683204
TI  - Criteria for choosing clinically effective glaucoma treatment: A discussion panel
      consensus.
AB  - Abstract. BACKGROUND: In the clinical management of patients at risk for or
      diagnosed with primary open-angle glaucoma (POAG), the aim of medical treatment
      is to reduce intraocular pressure (IOP) and then maintain it over time at a level
      that preserves both the structure and function of the optic nerve. OBJECTIVE: The
      objective of this report was to establish a consensus on the criteria that should
      be used to determine the characteristics of IOP-lowering medication. METHODS:
      Discussion was held among a panel of 12 physicians considered to be experts in
      glaucoma to develop a consensus on the criteria used by them to determine the
      characteristics of the IOP-lowering medication chosen for initial monotherapy and
      adjunctive treatment of ocular hypertension (OHT) or POAG. Consensus development
      combined available evidence and the impressions of these physicians regarding the
      clinical effectiveness of IOP-lowering medication for OHT and POAG. Once the
      panel identified the criteria, the order of priority and the relative importance
      of these criteria were then established in the setting of 3 risk categories (low,
      medium, and high) for a patient to experience significant visual disability from
      glaucoma over their expected life span. RESULTS: The panel identified 5 criteria
      to determine the characteristics of IOP-lowering medication for OHT and POAG: IOP
      lowering effect, systemic adverse events (AEs), ocular tolerability,
      compliance/administration, and cost of treatment. IOP-lowering effect was
      consistently ranked as the highest priority and cost as the lowest. The priority
      of compliance/administration did not vary by clinical situation. Systemic AEs and
      ocular tolerability were ranked as higher priorities in initial monotherapy than
      in adjunctive treatment and ranked lower as the risk for visual disability
      increased. The priority given to the criteria used to determine clinical
      effectiveness varied both with the risk for functional vision loss from glaucoma
      and whether initial monotherapy or adjunctive treatment was being considered.
      CONCLUSION: Glaucoma treatment should be assessed with regard to the need not
      only to lower IOP but also to minimize systemic and ocular AEs, promote patient
      compliance, and minimize cost. The order of priority and relative importance
      given to these treatment criteria will vary as part of individualizing patient
      care.

PMID- 24683206
TI  - Prevalence of Helicobacter pylori in symptomatic patients and detection of
      clarithromycin resistance using melting curve analysis.
AB  - Abstract. BACKGROUND: Clarithromycin is often a component of combination
      therapies for Helicobacter pylori eradication; however, increases in resistance
      rates have decreased the success of the treatment. OBJECTIVE: This study was
      designed to determine the prevalence of H pylori infection in symptomatic
      patients and to detect clarithromycin resistance rates using melting curve
      analysis. METHODS: Patients scheduled for upper endoscopy at the Endoscopy Unit
      of the Department of Gastroenterology, Duzce University, Medical Faculty
      Hospital, Konuralp/Duzce, Turkey, were assessed for enrollment in the study. Two
      pairs of gastric biopsy specimens (antrum and corpus) were obtained from each
      study patient. Histopathologic examination, rapid urease test, culture, and
      polymerase chain reaction (PCR) of the specimens were used to identify H pylori
      infection. Clarithromycin resistance was detected using melting curve analysis.
      RESULTS: Seventy-five patients (41 women, 34 men; mean [SD]age, 42.6 [14.5] years
      [range, 17-70 years]) were included in the study. Using histopathology and rapid
      urease test, H pylori was detected in 40 (53.3%) of the 75 specimens. H pylori
      was detected using PCR in 40 (53.3%) specimens and by culture in 10 (13.3%)
      specimens. The specificity and sensitivity of PCR and culture were interpreted by
      comparing them with the results of histopathologic examination and urease tests.
      The specificity and sensitivity of PCR were 68.6% and 72.5%, respectively, and
      the specificity and sensitivity of culture were 97.1% and 22.5%, respectively. Of
      the 40 isolates, 21 (52.5%) were susceptible to clarithromycin, 12 (30.0%) were
      resistant, and a mixed susceptibility pattern was detected in 7 (17.5%)
      specimens. H pylori isolates from 19 (79.2%) of the 24 patients who had formerly
      used clarithromycin showed clarithromycin resistance. CONCLUSIONS: The prevalence
      of H pylori infection was 53.3% for the symptomatic patients in this study, and
      47.5% of the isolates showed clarithromycin resistance using melting curve
      analysis. The PCR-based system used in this study was accurate for the detection
      of H pylori infection as well as clarithromycin susceptibility testing directly
      in biopsy specimens.

PMID- 24683205
TI  - Effectiveness of polymer-coated extended-release morphine sulfate capsules in
      older patients with persistent moderate-to-severe pain: A subgroup analysis of a
      large, open-label, community-based trial.
AB  - Abstract. BACKGROUND: Opioid analgesics may offer benefits over nonopioids in
      some older patients, especially those with moderate-to-severe pain. Polymer
      coated extended-release morphine sulfate (P-ERMS) has been found to be
      efficacious and well tolerated in patients with chronic, moderate-to-severe,
      nonmalignant pain when used QD or BID. OBJECTIVE: The purpose of this analysis
      was to determine the effectiveness of P-ERMS in older patients (aged >65 years)
      with persistent, moderate-to-severe, inadequately controlled, nonmalignant pain.
      METHODS: This was a subgroup analysis of the older population from an openlabel
      trial in community-based pain clinics in which patients underwent treatment with
      P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant
      pain (>=4 on a scale of 0-10). Patients received P-ERMS at a dose determined by
      the investigator based on their previous analgesic regimen, QD (morning or
      evening) for a 4-week treatment period. Dose increases were permitted after weeks
      1 and 2; switching to BID was allowed after week 2, if needed. Measurements
      included changes in pain and sleep scores (0-10 scale), quality of life (QOL)
      scores (physical and mental component summaries [PCS and MCS, respectively] of
      the 36-Item Short-Form Health Survey instrument), and patient and clinician
      assessments of current treatment based on a 9-point scale ranging from -4 to +4.
      RESULTS: One hundred forty-eight older patients (mean [SD]age, 73.4 [5.5] years)
      began treatment with P-ERMS; 86 (58.1%) of those patients completed the study.
      Pain and sleep scores significantly improved (decreased) from baseline to week 4
      (7.4 vs 5.0 and 5.0 vs 3.2, respectively; both, P < 0.001). PCS and MCS scores
      significantly improved (increased) from baseline (27.7 vs 31.6 and 37.6 vs 40.8,
      respectively; both, P < 0.05), as did patient and clinician global assessments (
      1.2 vs 1.1 and -1.5 vs 1.4; both, P < 0.001). Results found in these older
      patients were similar to those observed in the younger patients (aged <=65
      years). A majority (71.4%) of the older patients remained on QD administration
      and took significantly lower mean daily doses than younger patients (77.0 vs
      105.2 mg/d, respectively; P = 0.001). The dropout rate for the subgroup was
      41.1%, which was similar to that reported in previous studies in mixed-age
      populations taking other extended-release morphine formulations. Of the patients
      who discontinued (n = 60), adverse events (AEs) were the most prevalent reason (n
      = 29). The most common treatment-related AEs were constipation (19.6%) and nausea
      (9.5%). CONCLUSIONS: This subgroup analysis of a previously published study
      revealed that the older patients in that study who were receiving P-ERMS for
      persistent, moderate-to-severe, inadequately controlled, nonmalignant pain who
      completed the study attained significant improvements in pain, sleep, and QOL
      scores compared with baseline. Patient and clinician satisfaction with treatment
      increased significantly from baseline to study end. Older patients utilized
      significantly lower mean daily doses than younger patients (P < 0.001), and >70%
      remained on a QD administration regimen for the duration of the study.

PMID- 24683207
TI  - Perioperative use of eicosapentaenoic acid and patency of infrainguinal vein
      bypass: A retrospective chart review.
AB  - Abstract. BACKGROUND: A significant proportion of autogenous vein grafts fail in
      the long term. Currently, there is no treatment to improve graft patency.
      OBJECTIVE: This study was designed to assess the effectiveness of
      eicosapentaenoic acid (EPA) to prevent late failure of an autogenous vein graft
      and other perioperative risk factors affecting long-term patency. METHODS: A
      retrospective chart review was performed on grafts of patients who underwent
      infrainguinal bypass surgery using autogenous vein grafts for peripheral arterial
      disease in a lower limb. Patients were stratified by the perioperative use of
      EPA. The EPA group was those patients who administered EPA >=1 time within 3
      months of surgery. The non-EPA group was made up of those patients who did not
      administer EPA within 3 months of surgery. Primary, assisted primary, and
      secondary patency rates of the grafts in each group were calculated by the Kaplan
      Meier method and compared by the log-rank test. To evaluate the effect of other
      perioperative risk factors, a Cox proportional hazards analysis was performed.
      RESULTS: One hundred sixty-one grafts were analyzed from 159 patients who
      underwent surgery between July 1991 and July 2005. The primary patency rates of
      the EPA and non-EPA groups were 93% and 86%, 89% and 74%, and 83% and 68% at 1,
      3, and 5 years, respectively. In terms of primary patency, the EPA group was
      significantly better than the non-EPA group (P=0.042). There was no significant
      difference between the groups in either assisted primary or secondary patency. A
      Cox proportional hazard analysis found that the minimum graft diameter and
      perioperative use of EPA were significant factors for primary patency (P=0.002
      and P=0.004, respectively). Graft diameter was the only significant factor for
      assisted primary and secondary patency (P=0.021 and P=0.003, respectively).
      CONCLUSION: Although graft diameter was the most important factor for long-term
      patency of infrainguinal vein bypass grafts, the perioperative use of EPA
      significantly improved primary patency among these subjects.

PMID- 24683208
TI  - Effects of milrinone and olprinone on hypercapnic depression of diaphragmatic
      contractility in pentobarbital-anesthetized dogs.
AB  - Abstract. BACKGROUND: Hypercapnia is associated with diaphragm muscle dysfunction
      that is a reduction of diaphragmatic force generated for stable electric
      myographic activity. OBJECTIVE: The purpose of this study was to test the effects
      of milrinone and olprinone on decreased diaphragmatic contractility induced by
      hypercapnia in pentobarbital-anesthetized dogs. METHODS: This experimental study
      was conducted at the Department of Anesthesiology, University of Tsukuba,
      Institute of Clinical Medicine, Tsukuba, Japan. Hypercapnia (partial pressure of
      carbon dioxide [CO2] in arterial blood 80-90 mm Hg) was induced by adding 10% CO2
      to the inspired gas. When hypercapnia was established, group 1 received no study
      drug, group 2 was infused with milrinone (50 g/kg initial dose plus 0.5 g/kg .
      min(-1) thereafter), and group 3 was infused with olprinone (10 g/kg initial dose
      plus 0.3 g/kg . min(-1) thereafter). Diaphragmatic contractility was assessed by
      transdiaphragmatic pressure (Pdi). RESULTS: Twenty-four, healthy, adult mongrel
      dogs were used in the study; 8 dogs were assigned to each treatment group. In the
      presence of hypercapnia, in each group, Pdi (mean [SD], cm-H2O) at low-frequency
      (20 Hz) and highfrequency (100 Hz) stimulation significantly decreased from
      baseline (group 1: 20 Hz, 15.1 [2.4] vs 13.3 [2.7]; 100 Hz, 23.1 [2.7] vs 20.6
      [2.5], both, P = 0.001; group 2: 20 Hz, 15.2 [2.0] vs 13.2 [2.5]; 100 Hz, 23.0
      [2.5] vs 20.5 [2.5], both, P = 0.001; group 3: 20 Hz, 15.0 [2.2] vs 13.2 [2.1];
      100 Hz, 23.0 [2.5] vs 20.5 [2.7], both, P = 0.001). In group 1, the change in Pdi
      with regard to each stimulus was not significant when compared with the
      hypercapnia-induced values. In groups 2 and 3, during study-drug administration,
      Pdi increased significantly in response to both stimuli compared with hypercapnia
      induced values (group 2: 20 Hz, 13.2 [2.5] vs 18.8 [2.2]; 100 Hz, 20.5 [2.5] vs
      27.7 [2.3], both, P = 0.001; group 3: 20 Hz, 13.2 [2.1] vs 22.3 [3.5]; 100 Hz,
      20.5 [2.7] vs 30.8 [2.2], both, P = 0.001). The increase in Pdi with both stimuli
      was significantly greater in group 3 than in group 2 (20 Hz, 22.3 [3.5] vs 18.8
      [2.2], P = 0.035; 100 Hz, 30.8 [2.2] vs 27.7 [2.3], P = 0.046). CONCLUSIONS: The
      results of this experimental study of the effects of milrinone and olprinone on
      hypercapnic depression of diaphragmatic contractility in these pentobarbital
      anesthetized dogs suggest that olprinone and milrinone significantly improved
      diaphragm muscle dysfunction induced by hypercapnia. The effects of olprinone
      were significantly greater than those of milrinone. Further studies are needed to
      determine the optimal dose of the study drugs.

PMID- 24683209
TI  - Lens concentration of ofloxacin and lomefloxacin in an experimental
      endophthalmitis model.
AB  - Abstract. BACKGROUND: Bacterial endophthalmitis is a serious complication of
      ocular surgery and penetrating trauma. The primary causative organisms are
      strains of Staphylococcus aureus and Staphylococcus epidermidis. Fluoroquinolones
      are widely used to treat endophthalmitis. There are a few studies on the
      penetration of fluoroquinolones into the lens in inflamed eyes. A literature
      search did not identify any data regarding penetration of topical ofloxacin into
      the lens in normal and inflamed eyes. OBJECTIVE: The aim of this study was to
      determine the penetration of topical ofloxacin and lomefloxacin into the lens in
      a rabbit endophthalmitis model. METHODS: New Zealand white rabbits were randomly
      divided into 2 groups. The left eyes were infected with an intravitreal
      inoculation of S aureus. The right eyes were used as a noninoculated control.
      Groups 1 and 2 received topical ofloxacin and lomefloxacin treatment,
      respectively, 24 hours after the inoculation. Two drops of the study drugs were
      instilled in the eyes every 30 minutes for 3 hours and then every 60 minutes for
      3 hours. Lens samples were obtained 30 minutes after the last ofloxacin or
      lomefloxacin drops were administered. High-performance liquid chromatography was
      used to determine the fluoroquinolone concentration. RESULTS: Ten rabbits were
      equally divided into the 2 treatment groups. There was no significant difference
      in mean (SD) lens concentrations between the control and inoculated eyes in
      either treatment group-ofloxacin (0.26 [0.32] MUg/mL vs 0.11 [0.05] MUg/mL,
      respectively) and lomefloxacin (0.50 [0.87] MUg/mL vs 0.12 [0.08] MUg/mL,
      respectively). CONCLUSION: The results of this small experimental study found
      that topical ofloxacin and lomefloxacin can accumulate in the crystalline lens
      after installation. Inflammation did not affect the penetration of ofloxacin or
      lomefloxacin into the lens.

PMID- 24683210
TI  - Clinical evaluation of incadronate in korean patients with malignancy-associated
      hypercalcemia: An open-label, multicenter study.
AB  - Abstract. BACKGROUND: Incadronate has been found to lessen the increase in
      corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a
      Phase III study in Japan. The drug is currently used to treat MAH in Japan.
      OBJECTIVE: The purpose of this study was to assess the clinical usefulness of
      incadronate in patients with MAH. METHODS: This open-label study was conducted at
      3 medical institutions in Korea. Korean patients with MAH (corrected serum
      calcium levels >=11.0 mg/dL) were given a single 10-mg IV infusion of incadronate
      over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels
      were determined and subjective symptoms and objective findings (ie, bone pain,
      spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite,
      nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of
      consciousness) were used to monitor the effectiveness of the drug for 6 days
      after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3
      = severe). Adverse events (AEs) were identified by patients' reports, and adverse
      drug events (ADEs) were assessed by the investigators throughout the study.
      RESULTS: Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5
      years) were included in the study; data from 22 and 24 patients were used to
      assess effectiveness and tolerability, respectively. Corrected serum calcium
      level was significantly decreased on day 6 after treatment compared with
      pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P <
      0.001). The antihypercalcemic effect of incadronate became apparent as an
      inhibition of bone absorption a few days after infusion. Corrected serum calcium
      level was significantly decreased on days 2 to 6 (P < 0.001) after treatment
      compared with pretreatment at baseline. Evaluation of symptoms showed significant
      improvement in the incadronate-treated group (mean total score [range] at
      baseline, 8 [1-23] and day 6, 5.5 [1-17]; P = 0.001). Eight (33.3%) of the
      patients were found to have ADEs. Some of the 8 patients experienced >1 ADE (mild
      and transient fever [13 events], chills [3], headache [1], and myalgia [1]). AEs
      were observed in 19 (79.2%) of 24 patients. The most frequently reported AE was
      fever (14 events). CONCLUSION: In this small, open-label study, Korean subjects
      with MAH treated with incadronate experienced significant improvement in symptoms
      and calcium levels from baseline.

PMID- 24683211
TI  - Efficacy of preventive analgesia with tramadol or lornoxicam for percutaneous
      nephrolithotomy: a prospective, randomized, double-blind, placebo-controlled
      study.
AB  - BACKGROUND: Prevention of postoperative pain provides better and more rapid
      convalescence for patients. OBJECTIVE: The aim of this study was to compare the
      preventive analgesic effect of tramadol and lornoxicam in the early postoperative
      period in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS:
      Patients who were scheduled for elective PCNL at the Cumhuriyet University
      Hospital, Sivas, Turkey, were enrolled in this prospective, double-blind, placebo
      controlled study. The patients were randomly assigned to 1 of 3 groups: tramadol,
      lornoxicam, and normal saline (NS). Ten minutes before induction of anesthesia,
      the tramadol group received tramadol 100 mg IV, the lornoxicam group received
      lornoxicam 8 mg IV, and the NS group received NS 2 mL IV. Anesthesia was induced
      using fentanyl 1 MUg/kg and thiopental sodium 4 to 7 mg/kg. Vecuronium 0.1 mg/kg
      was used for muscle relaxation. Desflurane 4% to 6% and 50%:50% oxygen/nitrous
      oxide were used for maintenance. Oxygen saturation, heart rate, and mean blood
      pressure were recorded before induction and during the postoperative period.
      During the postoperative period, visual analogue scale O/AS) scores, time to
      first analgesic (TFA), total analgesic consumption (TAC), and patient
      satisfaction scores were determined. Data about postoperative nausea and vomiting
      and other adverse events and complications were also collected. RESULTS: Seventy
      three patients were assessed for enrollment and 60 (33 women, 27 men; mean [SD]
      age, 44.69 [11.27] years; age range, 20-62 years) were included in the study. The
      baseline demographic characteristics and duration of surgery were similar in all
      3 groups. The mean (SD) VAS scores in the tramadol group were significantly lower
      than in the NS group at 15 and 30 minutes and 1, 2, 4, and 12 hours after surgery
      (all, P < 0.05). The VAS scores in the lornoxicam group were significantly lower
      than in the NS group at 15 and 30 minutes and 1 hour (all, P < 0.05). The VAS
      score at 1 hour after surgery was significantly lower in the tramadol group than
      in the lornoxicam group (18 [8] vs 32 [16]; P < 0.05); however, there were no
      other significant differences in VAS scores between the active groups. A
      significantly shorter TFA was associated with the NS group when compared with the
      tramadol and lornoxicam groups (46 [27] vs 354 [187] and 180 [118], respectively;
      both, P < 0.05). TFA was significantly shorter in the lornoxicam group when
      compared with the tramadol roup (180 [118] vs 354 [187]; P < 0.05). TAC was
      significantly higher in the NS group than in the tramadol and lornoxicam groups
      (270 [47] vs 115 [74] and 145 [72], respectively; both, P < 0.05). Patient
      satisfaction score (range) was significantly lower in the NS group when compared
      with the tramadol and lornoxicam groups (0 [0-1] vs 3 [0-3] and 2 [0-3],
      respectively; both, P < 0.05). There were no other significant between-group
      differences observed. CONCLUSIONS: Tramadol and lornoxicam were more effective
      than NS in preventing early postoperative pain. The preventive analgesic effect
      of tramadol was comparable with that of lornoxicam, except at 1 hour when
      tramadol was more effective among these patients undergoing PCNL. Both drugs were
      well tolerated.

PMID- 24683212
TI  - Serum osteoprotegerin concentration with strontium ranelate treatment for
      postmenopausal osteoporosis: an open, prospective study.
AB  - BACKGROUND: Strontium ranelate (SR) is a new antiosteoporotic agent with
      antiresorptive and bone-forming properties. The exact mechanism by which SR
      exerts its effects is not clearly understood. Bone resorption requires
      interaction between osteoblasts and osteoclasts. Osteoblasts produce a ligand for
      receptor activator of nuclear factor-kappaB (RANK). They also secrete
      osteoprotegerin, a decoy protein that blocks the interaction of RANK with its
      ligand, thereby inhibiting the differentiation and activity of osteoclasts. SR
      also has been associated with osteoblast proliferation and decreased osteoblast
      induced osteoclast differentiation via increased osteoprotegerin messenger RNA
      expression in human osteoblasts. OBJECTIVE: The aim of this study was to
      investigate the relationship between SR treatment and serum osteoprotegerin
      concentration in women with post-menopausal osteoporosis (PMO). METHODS: This
      open, prospective study was conducted in women admitted to the outpatient
      endocrinology clinic of Baskent University Faculty of Medicine, Adana Medical
      Center, Ankara, Turkey, for the evaluation of PMO. Women with PMO who enrolled
      were administered elemental calcium 1000 mg/d and vitamin D 800 IU/d for 1 month
      before the study period. After obtaining baseline serum samples for determining
      osteoprotegerin concentrations, patients were assigned to the treatment or
      control groups at a 5:2 ratio and SR 2 g/d was administered to the treatment
      group. The control group continued to receive only calcium and vitamin D. Serum
      osteoprotegerin concentration was measured again after 3 months of treatment.
      RESULTS: Thirty-five women (treatment group: n = 25; mean [SD] age, 59.80 [7.38]
      years; control group: n = 10; mean [SD] age, 56.60 [5.06] years) enrolled in the
      study. A total of 32 women-24 in the treatment group and 8 in the control group
      completed the study. Compared with baseline, mean [SD] serum osteoprotegerin
      concentration did not change significantly after 3 months in either the treatment
      group (4.91 [1.24] pmol/L vs 4.71 [1.19] pmol/L) or the control group (5.36
      [2.82] pmol/L vs 5.10 [2.19] pmol/L). CONCLUSION: The results of this small study
      found that serum osteoprotegerin concentrations were not significantly changed by
      SR treatment for 3 months among women with PMO.

PMID- 24683213
TI  - Effects of flutamide on [methyl-(3)h]-choline uptake in human prostate cancer-3
      cells: a pilot study.
AB  - BACKGROUND: Positron emission tomography using [methyl-(11)C]-choline is
      effective in imaging many types of cancer, especially prostate cancer (PC). The
      antiandrogen flutamide is often used as part of the initial treatment of PC. Data
      on the effect of flutamide on and methylcholine incorporation into PC-3 cells are
      lacking in the experimental and literature work. OBJECTIVES: The aims of this
      study were to assess whether human PC-3 cells are susceptible to flutamide and
      whether the drug modulates the uptake of [methyl-(3)H]-choline into these cells.
      METHODS: PC-3 cells were treated for 3 days with flutamide (<=100 nmol/L),
      inhibiting growth by 20% to 70% with control cells included. Two viability tests
      (cytotoxic analyses), the thiazole blue assay and the trypan blue exclusion
      method, were used to determine the median inhibitory concentration for flutamide
      (10 nmol/L). Control and flutamide-treated cells were incubated with [methyl
      (3)H]-choline for 10 minutes and then in nonradioactive medium for 10 minutes to
      simulate the rapid blood clearance of [methyl-(11)C]-choline tracer that occurs
      within 5 to 20 minutes, and then extracted using organic and aqueous solvents to
      determine the intracellular distribution of the tracer. Protein assay and flow
      cytometry analysis were used to determine protein content and DNA synthesis in
      both control and treated cells. The uptake of [methyl-(3)H]-choline was
      normalized to protein content and expressed as mean (SD) dpm/1Jg protein (n = 6).
      RESULTS: PC-3 cell proliferation was inhibited with flutamide treatment. After
      treatment of PC-3 cells with flutamide 10 nmol/L for 3 days, cells accumulated
      DNA during the S phase. Mean (SD) [methyl-(3)H]-choline uptake was found to be
      significantly lower with flutamide 10-nmol/L-treated cells compared with control
      cells (65.95 [0.72] vs 114.21 [0.57] dpm/1Jg protein; P < 0.001); the difference
      between the 5-nmol/L-treated cells and controls was nonsignificant. CONCLUSIONS:
      In this pilot study, flutamide inhibited tumor cell growth and proliferation and
      decreased (modulated) the uptake of [methyl-(3)H]-choline into androgen receptor
      negative PC-3 cells. These results suggest that flutamide might inhibit
      proliferation by an androgen-independent mechanism.

PMID- 24683214
TI  - Comparison of the antibacterial activity of lidocaine 1% versus alkalinized
      lidocaine in vitro.
AB  - BACKGROUND: Infections after epidural and spinal blocks are rare. The topical
      anesthetic liclocaine used in these procedures has been found to have
      antibacterial effects on various microorganisms. OBJECTIVE: The aim of this study
      was to assess the antibacterial effects of alkalinized liclocaine on
      Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. METHODS:
      Lidocaine 2%, alkalinized lidocaine, and physiologic saline (as a control
      solution) were added to standard bacterial preparations. The final concentration
      of the lidocaine was 10 mg/mL (1%). At baseline and 3 and 6 hours after
      incubation at 37 degrees C, 3-mL aliquots were vortexed and pipetted into sterile
      polystyrene spectrophotometer cuvettes. Baseline referred to the end of the
      period of preparation of the solution (<=20 minutes). Growth was measured as the
      optical density at a wavelength of 540 nm. RESULTS: Compared with the control,
      lidocaine significantly inhibited the growth of S aureus, E coli, and P
      aeruginosa at baseline and 3 and 6 hours after incubation (all, P < 0.05).
      Alkalinized lidocaine significantly inhibited the growth of S aureus at baseline
      and 3 and 6 hours (all, P < 0.05), while it significantly inhibited the growth of
      E coli and P aeruginosa only at 6 hours (both, P < 0.05). The growth of E coli
      was significantly less in lidocaine than in alkalinized lidocaine at 0 and 3
      hours (both, P < 0.05). CONCLUSION: The antibacterial effect of lidocaine 1% on S
      aureus was not changed after alkalinization. The effect of alkalinized lidocaine
      on E coli and P aeruginosa was significant only at 6 hours. Lidocaine
      significantly inhibited the growth of these 3 microorganisms at all study
      periods.

PMID- 24683215
TI  - Effects of (r,r)- and (r,r/s,s)-formoterol on airway relaxation and contraction
      in an experimental rat model.
AB  - BACKGROUND: Racemic (R,R/S,S)-formoterol is a long-acting beta-agonist composed
      of a 50:50 mixture of (R,R)- and (S,S)-enantiomers. OBJECTIVE: The aim of this
      study was to determine whether (R,R)-formoterol and (R,R/S,S)-formoterol have
      differing effects on airway contraction and relaxation in vitro. METHODS:
      Cylindrical airway segments 3-mm long were isolated from the mid-trachea of
      healthy Sprague-Dawley rats and placed in a modified Krebs-Henseleit solution.
      Dose-response curves of bethanechol-induced contraction (measured as milligrams
      of tension) and the concentration of bethanechol that elicited 50% to 75% of
      maximal contraction (EC50-75) were determined. The air-way cylinders were then
      precontracted with bethanechol at the EC50-75 and exposed to different
      concentrations of (R,R)-formoterol (0.0001-1.0 MUM) or (R,R/S,S)-formoterol
      (0.0002-2.0 MUM). Each concentration of the 2 formoterol formulations contained
      the same amount of (R,R)-enantiomer (eg, [R,R]-formoterol 0.0001 MUM and
      [R,R/S,S]-formoterol 0.0002 1JM contained the same amount of [R,R]-enantiomer).
      The relaxation percentage in response to formoterol was calculated as a reduction
      in tension (in milligrams) in relation to baseline tension in the precontracted
      state, with each tracheal cylinder serving as its own control. To determine the
      effect of (R,R)-formoterol on airway contraction, tracheal cylinders were
      incubated with (R,R)- or (R,R/S,S)-formoterol before electrical field stimulation
      (EFS). RESULTS: Tracheae from 56 three-week-old Sprague-Dawley rats were used in
      the study. The relaxation percentage of precontracted trachea was significantly
      greater after exposure to (R,R)-formoterol than to (R,R/S,S)-formoterol at a 2
      fold higher concentration (P = 0.03; general linear model with repeated measures
      analysis comparing the 2 groups of animals). However, in a post hoc analysis, the
      mean (SE) relaxation percentage of precontracted trachea was significantly
      greater only after exposure to (R,R)-formoterol 0.01 MUM than to (R,R/S,S)
      formoterol 0.02 MUM (15.6% [5.8%] vs 39.0% [5.6%]; P < 0.05, unpaired t test).
      EFS-induced airway contraction was significantly less in tracheal cylinders
      incubated in (R,R)-formoterol compared with those incubated in (R,R/S,S)
      formoterol at a 2-fold higher concentration (P = 0.05; general linear model with
      repeated measures analysis comparing the 2 groups of animals). However, in the
      post hoc analysis, mean (SE) EFS-induced tracheal contraction was significantly
      less only in (R,R)-formoterol 0.01 MUM compared with (R,R/S,S)-formoterol 0.02
      MUM at 10 V (1070 [55] mgvs 1225 [28] mg; P < 0.05, unpaired t test). CONCLUSION:
      We found that (R,R)-formoterol may induce greater relaxation of precontracted
      airway smooth muscle cells than (R,R/S,S)-formoterol and that (R,R)-formoterol
      may have a greater inhibitory effect on the endogenous cholinergic and excitatory
      nonadrenergic, noncholinergic contractile airway responses than (R,R/S,S)
      formoterol. We speculate that the presence of the (S,S)-enantiomer in (R,R/S,S)
      formoterol may impair airway relaxation of pre-contracted trachea in rats.

PMID- 24683216
TI  - Effects of zileuton on the development of autoimmune myocarditis in an
      experimental rat model.
AB  - BACKGROUND: Myocarditis is associated with high morbidity and mortality in
      childhood, but the pathogenesis of this disease is still unclear. Current
      knowledge indicates that complex immunopathogenic mechanisms are involved. It is
      understood that leukotrienes play an important role in the inflammation
      associated with asthma, and recent reports indicate that leukotrienes participate
      in immune processes and in autoimmunity. OBJECTIVE: The aim of this study was to
      assess the role of leukotriene synthesis in the development of myocardial
      inflammation and necrosis during myocarditis. METHODS: The effect of zileuton, a
      leukotriene synthesis inhibitor, was assessed in an experimental model of
      autoimmune myocarditis in rats. Healthy adult (10-week-old) male Wistar albino
      rats were randomly divided into 3 groups. Groups A and B received injections of
      1.0 mg porcine cardiac myosin to induce autoimmune myocarditis and group C (the
      control group) received phosphate-buffered saline. Group B also received zileuton
      by oral gavage at 100 mg/kg . d(-1). Myocardial inflammation was assessed
      biochemically via serum concentrations of creatine kinase MB subunit (CK-MB) and
      troponin T. Cardiac tissue was assessed macroscopically (0 = no inflammation; 1 =
      a small discolored focus; 2 = diffuse discolored areas covering less than half of
      the cardiac surface; 3 = diffuse discolored areas covering more than half of the
      cardiac surface) and microscopically (0 = no inflammation; 1 = ?5% infiltration;
      2 = 5% to <10% infiltration; 3 = 10% to < 20% infiltration; 4 = >20%
      infiltration). RESULTS: Twenty-four rats were divided equally into 3 groups. All
      rats survived the duration of the study. After 21 days, all rats were euthanized.
      No significant differences were found between groups A and B in terms of serum
      concentrations of CK-MB or troponin T. The microscopic pathology score was
      significantly lower in group B (myosin + zileuton) than in group A (myosin only)
      (0.12 [0.35] vs 1.25 [1.03]; P = 0.023). The microscopic pathology score was
      significantly higher in group A than in group C (1.25 [1.03] vs 0; P < 0.01), but
      the difference between groups B and C was not statistically significant. The
      macroscopic pathology score was significantly higher in group A than in group B
      (1.37 [0.91] vs 0.37 [0.51]; P = 0.029). The macroscopic pathology score was
      significantly higher in group A than in group C (1.37 [0.91] vs 0; P < 0.01).
      There was no significant difference in macroscopic scores between groups B and C
      (0.37 [0.51] vs 0). CONCLUSIONS: In this study of the effects of zileuton in an
      experimental rat model of autoimmune myocarditis, no significant differences were
      found in the serum concentrations of the biochemical markers in the 2 groups
      administered myosin. However, lower macroscopic and microscopic inflammation
      scores in the zileuton-treated group (group B) compared with the group
      administered only myosin (group A) suggest that zileuton, a leukotriene-synthesis
      inhibitor, may suppress the development of experimental autoimmune myocarditis in
      rats.

PMID- 24683217
TI  - Loss of smell (anosmia) and taste (ageusia) in a patient treated with pegylated
      interferon alfa and ribavirin.
AB  - INTRODUCTION: Anosmia, the loss of the sense of smell, is a rare adverse event
      associated with interferon alpha (INF-alpha). Millions of patients with hepatitis
      B and hepatitis C virus (HCV) infection are currently treated with INF-alfa-2a
      daily. Only 5 cases of anosmia have been reported in the literature, and none was
      associated with pegylated INF-alfa. CASE SUMMARY: A 55-year-old Arab male
      (height, 5'1"; weight, 81 kg) with chronic HCV developed anosmia and ageusia
      (loss of the sense of taste) after 36 weeks of treatment for HCV with
      subcutaneous pegylated INF-alfa-2a 180 MUg and ribavirin 1200 mg. Treatment was
      continued for 12 additional weeks before being discontinued. Twenty-four weeks
      after treatment was discontinued, HCV-RNA was undetectable and, during the same
      visit, the patient reported that he had regained his sense of smell a few weeks
      previously. The Naranjo algorithm score was 7, representing a probable
      association of anosmia with INF-alfa-2a treatment. Other etiologies for loss of
      smell and taste were ruled out. CONCLUSIONS: We report a case of anosmia and
      ageusia in a patient treated with pegylated INF-alfa-2b and ribavirin for HCV
      infection. The patient regained his sense of smell and taste within 24 weeks of
      stopping treatment.

PMID- 24683219
TI  - The Charles R. Ream, MD, award for excellence-2008.

PMID- 24683218
TI  - Comparison of the Addition of Siberian Ginseng (Acanthopanax senticosus) Versus
      Fluoxetine to Lithium for the Treatment of Bipolar Disorder in Adolescents: A
      Randomized, Double-Blind Trial.
AB  - BACKGROUND: Bipolar disorder (BD) is a common, recurrent, and often life-long
      major psychiatric condition characterized by manic, depressive, and mixed
      episodes. Without treatment, there is substantial risk for morbidity and
      mortality, making BD a considerable public health problem. OBJECTIVE: The purpose
      of this study was to compare the relative effectiveness and tolerability of
      Acanthopanax senficosus (A senficosus)-an herb that is derived from
      eleutherosides and polysaccharides found in the plant's root- versus fluoxetine
      added to lithium in the treatment of BD in adolescents. METHODS: This was a
      double-blind, 6-week study. The patients were randomized into 2 treatment groups
      A senticosus plus lithium (A senticosus group) and fluoxetine plus lithium
      (fluoxetine group). The patients underwent a baseline assessment using the 17
      Item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale
      (YMRS) during the screening period. Patients were scheduled for clinical visits
      at the end of weeks 1, 2, 4, and 6. At the end of the 6-week treatment period,
      each patient's condition was rated as follows: response (indicating an
      improvement of >=50% in the HAMD-17 score from baseline); remission (a HAMD-17
      score of ?7); and switching to mania (a YMRS score >16, and meeting the criteria
      of the Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition,
      Text Revision] for a manic episode). At each visit (with the exception of the
      enrollment visit), the patients were queried as to whether they experienced any
      health problems since the previous visit, a Treatment Emergent Symptom Scale
      assessment was completed, and the serum lithium concentration was analyzed. The
      patients were instructed to report adverse events (AEs) at any time during the
      study. AEs were also observed by the investigator(s) at clinical visits. RESULTS:
      Seventy-nine Chinese adolescents were initially enrolled into the study. However,
      76 adolescents were assessed for inclusion (45 females, 31 males; mean [SD] age,
      15.4 [30.0] years; age range, 12-17 years) in the study. All included patients
      completed the study. After 6 weeks of treatment, the response rate between the A
      senticosus and the fluoxetine groups was similar (67.6% vs 71.8%, respectively).
      The remission rate between both groups was also similar (51.4% vs 48.7%).
      Analyzed by a general line model, the HAMD-17 scores revealed there was a
      significant time effect (F = 183.06; P < 0.01), but not a significant group
      effect (F = 0.99) or group-by-duration of treatment interaction (F = 0.779).
      Three patients in the fluoxetine group experienced switching to mania compared
      with no patient in the A senticosus group. AEs reported by patients in the A
      senticosus group were as follows: nausea, 2 (5.4%); rash, 1 (2.7%); and diarrhea,
      1 (2.7%). AEs reported by patients in the fluoxetine group were as follows:
      nausea, 4 (10.3%); anxiety, 3 (7.7%); insomnia, 3 (7.7%); constipation, 1 (2.6%);
      and tinnitus, 1 (2.6%). CONCLUSION: Our study found no significant difference in
      these adolescents with BD treated with lithium plus adjunctive A senticosus or
      fluoxetine. All treatments were generally well tolerated.

PMID- 24683220
TI  - Effects of atorvastatin 10 mg and fenofibrate 200 mg on the low-density
      lipoprotein profile in dyslipidemic patients: A 12-week, multicenter, randomized,
      open-label, parallel-group study.
AB  - BACKGROUND: Elevated plasma low-density lipoprotein cholesterol (LDL-C)
      concentrations are highly atherogenic, especially the small, dense LDL (sdLDL)
      species. Fenofibrate has been reported to shift the LDL profile by decreasing the
      sdLDL subfraction and increasing larger LDL subclasses. Atorvastatin,
      anantihyperlipidemic agent, has been reported to reduce plasma total cholesterol
      (TC) and triglyceride (TG) concentrations and thus could modify the LDL profile.
      OBJECTIVE: The aim of this study was to compare the effects of fenofi brate and
      atorvastatin on standard lipid concentrations and the LDL profile. METHODS: In
      this randomized, open-label, parallel-group study, men and women aged 18 to 79
      years with type II primary dyslipidemia, defined as LDL-C >=160 and TG 150 to 400
      mg/dL, after a 4- to 6-week washout period while eating an appropriate diet, were
      randomized to receive either atorvastatin 10 mg once daily or fenofi-brate 200 mg
      once daily. Plasma lipid concentrations and cholesterol and apolipoprotein (apo)
      B (reflecting the LDL particle number) in each LDL subfraction prepared by
      ultracentrifiigation were determined at baseline and after 12 weeks of treatment.
      Tolerability was assessed using adverse events (AEs) obtained on laboratory
      analysis and vital sign measurement. Adherence was assessed by counting unused
      drug supplies. RESULTS: A total of 165 patients (117 men, 48 women; mean [SD]
      age, 50.1 [10.7] years; mean TC concentration, 289 mg/dL) were randomized to
      receive atorvastatin (n = 81) or fenofibrate (n = 84). Compared with fenofibrate,
      atorvastatin was associated with a significantly greater mean (SD) percentage
      decrease in TC (27.0% [12.3%] vs 16.5% [12.9%]; P < 0.001), calculated LDL-C
      (35.4% [15.8%] vs 17.3% [17.2%]; P < 0.001), TC/high-density lipoprotein
      cholesterol (HDL-C) ratio (29.1% [16.3%] vs 22.9% [15.9%]; P = 0.001), and apoB
      (30.3% [12.7%] vs 19.6% [15.5%]; P < 0.001). Compared with atorvastatin,
      fenofibrate was associated with a significantly greater decrease in TG (37.2%
      [25.9%] vs 20.2% [27.3%]; P < 0.001) and a significantly greater increase in HDL
      C concentration (10.4% [15.7%] vs 4.6% [12.1%]; P = 0.017). Fibrinogen
      concentration was significantly different between the 2 groups (P = 0.002); it
      was decreased with fenofibrate use (4.6% [23.7%]) and was increased with
      atorvastatin use (5.7% [23.5%]). Atorvastatin did not markedly affect the LDL
      distribution; it was associated with a homogeneous decrease in cholesterol and
      apoB concentrations in all subfractions, whereas fenofibrate was associated with
      a marked movement toward a normalized LDL profile, shifting the sdLDL
      subfractions toward larger and less atherogenic particles, particularly in those
      patients with baseline TG >=200 mg/dL. No serious AEs related to the study
      treatments were reported. A total of 5 AEs were observed in 8 patients,
      including: abdominal pain, 3 patients (2 in the atorvastatin group and 1 in the
      fenofibrate group); abnormal liver function test results, 1 (fenofibrate);
      increased creatine Phosphokinase activity, 2 (atorvastatin); gastrointestinal
      disorders, 1 (fenofibrate); and vertigo, 1 (fenofibrate). CONCLUSION: In these
      dyslipidemic patients, fenofibrate treatment was associated with an improved LDL
      subfraction profile beyond reduction in LDL-C, particularly in patients with
      elevated TG concentration, whereas atorvastatin was associated with equally
      reduced concentrations of cholesterol and apoB in all LDL subfractions
      independent of TG concentrations.

PMID- 24683221
TI  - Comparison of recovery characteristics, postoperative nausea and vomiting, and
      gastrointestinal motility with total intravenous anesthesia with propofol versus
      inhalation anesthesia with desflurane for laparoscopic cholecystectomy: A
      randomized controlled study.
AB  - BACKGROUND: Clinical effects, recovery characteristics, and costs of total
      intravenous anesthesia with different inhalational anesthetics have been
      investigated and compared; however, there are no reported clinical studies
      focusing on the effects of anesthesia with propofol and desflurane in patients
      undergoing laparoscopic cholecystectomy. OBJECTIVE: The aim of this study was to
      determine the effects of total intravenous anesthesia with propofol and
      alfentanil compared with those of desflurane and alfentanil on recovery
      characteristics, postoperative nausea and vomiting (PONV), duration of
      hospitalization, and gastrointestinal motility. METHODS: Patients classified as
      American Society of Anesthesiologists physical status I or II undergoing elective
      laparoscopic cholecystectomy due to benign gallbladder disease were enrolled in
      the study. Patients were randomly assigned at a 1:1 ratio to receive total
      intravenous anesthesia with propofol (2-2.5 mg/kg) and alfentanil (20 MUg/kg) or
      desflurane (4%-6%) and alfentanil (20 MUg/kg). Perioperative management during
      premedication, intraoperative analgesia, relaxation, ventilation, and
      postoperative analgesia were carried out identically in the 2 groups. Extubation
      time, recovery time, PONV, postoperative antiemetic requirement, time to
      gastrointestinal motility and flatus, duration of hospitalization, and adverse
      effects were recorded. Postoperative pain was assessed using a visual analogue
      scale. RESULTS: Sixty-eight patients were assessed for inclusion in the study; 5
      were excluded because they chose open surgery and 3 did not complete the study
      because they left the hospital. Sixty patients (33 women, 27 men) completed the
      study. Recovery time was significantly shorter in the propofol group (n = 30)
      compared with the desflurane group (n = 30) (8.0 [0.77] vs 9.2 [0.66] min,
      respectively; P < 0.005). Fifteen patients (50.0%) in the propofol group and 20
      patients (66.7%) in the desflurane group experienced nausea during the first 24
      hours after surgery. The difference was not considered significant. In the
      propofol group, significantly fewer patients had vomiting episodes compared with
      those in the desflurane group (2 [6.7%] vs 16 [53.3%]; P < 0.005). Significantly
      fewer patients in the propofol group required analgesic medication in the first
      24 hours after surgery compared with those in the desflurane group (10 [33.3%] vs
      15 [50.0%]; P < 0.005). Patients in the propofol group experienced bowel
      movements in a significantly shorter period of time compared with patients in the
      desflurane group (8.30 [1.67] vs 9.76 [1.88] hours; P = 0.02). The mean time to
      flatus occurred significantly sooner after surgery in the propofol group than in
      the desflurane group (8.70 [1.79] vs 9.46 [2.09] hours; P = 0.01). The duration
      of hospitalization after surgery was significantly shorter in the propofol group
      than in the desflurane group (40.60 [3.49] vs 43.60 [3.56] hours; P = 0.03).
      CONCLUSION: Total intravenous anesthesia with propofol and alfentanil was
      associated with a significantly reduced rate of PONV and analgesic consumption,
      shortened recovery time and duration of hospitalization, accelerated onset of
      bowel movements, and increased patient satisfaction compared with desflurane and
      alfentanil in these patients undergoing laparoscopic surgery who completed the
      study.

PMID- 24683222
TI  - Single-dose bioequivalence assessment of two formulations of polysaccharide iron
      complex capsules in healthy adult male Chinese volunteers: A sequence-randomized,
      double-blind, two-way crossover study.
AB  - BACKGROUND: Iron deficiency anemia (IDA) is a common nutritional disease
      worldwide. Iron supplementation is an efficient method for treating patients with
      IDA. Polysaccharide iron complex is an oral iron supplement that is associated
      with generally good tolerability and good bioavailability. OBJECTIVE: The aim of
      this study was to evaluate the bioequivalence of 2 branded formulations of
      polysaccharide iron complex in healthy adult male Chinese volunteers by
      determining the pharmacokinetic parameters after single-dose oral admi ni strati
      on. METHODS: This sequence-randomized, double-blind, 2-way crossover study was
      carried out in the Affiliated Hospital, Institute of Medical Sciences of Qingdao
      University, Qingdao, China. Healthy adult male Chinese volunteers were enrolled
      and evenly randomized to receive 1 of 2 formulations on day 1. Subjects received
      an oral dose of 150 mg (1 capsule) of polysaccharide iron complex with 150 mL of
      warm water in the morning. Capsules were of similar size, shape, and color to
      ensure blinding. Four hours after administration, the subjects were given
      standardized meals. After a 1-week washout period, the subjects were crossed over
      to receive the other formulation in a similar manner. The serum iron
      concentration 12 hours after study drug administration was determined using
      atomic-absorption spectrometry. The pharmacokinetic parameters Cmax, Tmax, AUC0
      t, and AUC0-infinity were obtained and analyzed using the Schuir mann 2 one-sided
      t test. The 2 formulations were considered bioequi valent if the test/reference
      ratios of Cmax, AUC0-t, and their 90% CIs were within the range of 70% to 143%
      for Cmax and within 80% to 125% for AUC0-t. Tolerability was monitored by
      inquiring whether the subjects had experienced adverse events (AEs), with a focus
      on gastrointestinal AEs, during the clinic visits during the 24-hour period after
      drag administration and subsequently via telephone throughout the study. RESULTS:
      Thirty adult male Chinese volunteers were assessed for inclusion. Twenty healthy
      male volunteers (10 in each group) (mean [SD] age, 21.5 [2.9] years [range, 19-23
      years]; weight, 66.2 [5-8] kg [range, 56-80 kg]; height, 172.5 [5.1] cm [range,
      162-180 cm]) were enrolled and completed the study. The pharmacokinetic
      parameters of the test and reference formulations were as follows: AUCO-t, 6.58
      (2.09) and 6.58 (1.91) MUg/mL . h(-1); Cmax, 1.10 (0.28) and 1.07 (0.25) MUg/mL;
      Tmax, 3.93 (0.37) and 3-93 (0.37) hours; t1/2, 8.33 (0.36) and 8.38 (0.41) hours;
      and AUC0-infinity, 6.93 (2.23) and 6.95 (2.13) MUg/mL . h(-1), respectively.
      There were no statistically significant differences in AUC0-infinity or Tmax by
      formulation, period, or subject between the test and reference formulations.
      Similarly, there were no statistically significant differences in Cmax by period;
      however, a significant difference was found in Cmax by formulation (P = 0.012).
      No clinically significant AEs were reported with either formulation. CONCLUSIONS:
      In these healthy adult male Chinese volunteers, the test formulation of
      polysaccharide iron complex was found to be bioequivalent to the reference
      formulation according to the Chinese regulatory definition. A significant
      difference by formulation was found in Cmax. The sample size was smaller than
      that recommended by the US Food and Drug Administration for a bioequivalence
      study, and additional studies with larger sample sizes are needed.

PMID- 24683223
TI  - The effects of cetuximab alone and in combination with endostatin on vascular
      endothelial growth factor and interleukin-8 expression in human lung
      adenocarcinoma cells.
AB  - BACKGROUND: Angiogenesis, the growth of new blood vessels, plays an important
      role in tumor growth and metastasis. Both cetuximab and endostatin have been
      found to reduce the expression of endothelial-stimulating growth factors such as
      vascular endothelial growth factor (VEGF) and interleukin (IL)-8. However, the
      effects of cetuximab alone or in combination with endostatin on human lung
      adenocarcinoma cell growth remain unclear. OBJECTIVE: The aim of this study was
      to evaluate the cellular and molecular effects of cetuximab alone and in
      combination with endostatin on human lung adenocarcinoma cell lines HI 299, SPC
      A1, and H460 in vitro. Methods The epidermal growth factor receptor (EGFR) status
      of a panel of human lung adenocarcinoma cell lines was characterized using
      Western blot analysis. We used a modified tetrazolium salt assay to evaluate the
      growth-inhibitory effects of cetuximab and endostatin alone and in combination on
      the cell lines. We also determined the effects of these 2 drugs on VEGF and IL-8
      expression using enzyme-linked immunosorbent assay (ELISA) and Western blot
      analysis. Cells were treated for 4 days with cetuximab 12.5 MU/mL, endostatin 25
      MU/mL, or cetuximab 12.5 MUg/mL + endostatin 25 MUg/mL. Untreated cells cultured
      for 4 days served as controls. RESULTS: EGFR expression in the H1299 cells was
      higher than in the SPC-A1 and H460 cells. Varying concentrations of cetuximab
      alone were associated with a significant growth-inhibitory effect on all 3 cell
      lines in a dose-dependent manner after 4 days of exposure compared with controls
      (all, P < 0.05). Compared with controls, varying concentrations of endostatin
      alone were not associated with significant inhibition of cell growth in any of
      the 3 cell lines. The inhibitory ratio of cetuximab + endostatin at varying
      concentrations was significantly greater than that of cetuximab alone (all, P <
      0.05). On ELISA, either drug alone was associated with significant reductions in
      secreted VEGF and IL-8 in the HI 299, SPC-A1, and H460 cell lines (all, P <
      0.05), with the exception of IL-8 concentration in the H460 cells. Mean (SD) VEGF
      expression with combination treatment in the H1299 and SPC-A1 cell lines (687
      [21] and 629 [23] pg/mL, respectively) was significantly lower than with cetuxi
      mab alone (878 [31] and 708 [20] pg/mL; both, P < 0.001); in the H460 cell line,
      combination treatment was not associated with a significant further reduction in
      VEGF expression. IL-8 concentrations with cetuximab in the H1299, SPC-A1, and
      H460 cell lines were 628 (20), 484 (29), and 532 (28) pg/mL, respectively, while
      the IL-8 concentrations with the combination treatment were 516 (20), 480 (18),
      and 467 (30) pg/mL. An enhanced effect of endostatin on IL-8 was observed in the
      H1299 and H460 cell lines (P < 0.001 and P = 0.018, respectively); however, no
      enhanced effect in the SPC-A1 line was observed. Similar results for VEGF and IL
      8 expression were found using Western blot analysis. CONCLUSIONS: The results
      from this in vitro study suggest that cetuximab treatment might both inhibit
      human lung adenocarcinoma cell line growth and reduce the expression of VEGF and
      IL-8, which are the biomarkers of angiogenesis. Endostatin was not associated
      with inhibition of human lung adenocarcinoma cell line growth directly. Findings
      with the combination of cetuximab + endostatin suggest that endostatin might
      enhance the antiangiogenic and antitumor activity of cetuximab through an
      apparent effect on VEGF expression and, to a lesser degree, on IL-8 expression.

PMID- 24683224
TI  - The effect of sumatriptan on nitric oxide synthase enzyme production after
      iatrogenic inflammation in the brain stem of adolescent rats: A randomized,
      controlled, experimental study.
AB  - BACKGROUND: Migraine is a common disabling disorder of childhood and adolescence.
      Despite advances in the understanding of migraine pathophysiology, treatment
      remains a challenge. OBJECTIVES: The aims of this study were to investigate the
      production of nitric oxide synthase (NOS) enzymes in the brain stem of adolescent
      rats, using an experimental model of migraine, and the effect of sumatriptan
      pretreatment on the production of the NOS enzymes. METHODS: Male adolescent (aged
      ~2 months) Wistar rats were used in the study. The animals were anesthetized
      using pentobarbital. The trigeminovascular system was stimulated by injecting a
      proinflammatory molecule, carrageenan, into the cis-terna magna of the
      anesthetized rats. The animals were divided into 3 groups of equal size: (1) the
      study group, in which the rats were treated with sumatriptan succinate 2 hours
      before intracisternal carrageenan injection; (2) the sham group, in which the
      rats were not administered intracisternal carrageenan injection or sumatriptan
      pretreatment; and (3) the control group, in which the rats were administered
      intracisternal carrageenan injection but were not pretreated with sumatriptan. In
      the control and study groups, the rats were euthanized using ether anesthesia 1
      hour after intracisternal carrageenan injection. Rats in the sham group were
      euthanized 1 hour after intracisternal catheterization. Brain tissue was removed
      and endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS)
      immunohistochemistry was performed. RESULTS: Twenty-one rats were randomized into
      3 groups of 7. The mean values of the immunolabeling intensities for eNOS, nNOS,
      and iNOS enzymes in the brain stem were significantly lower in the sham group
      compared with the control group (P = 0.001, P = 0.002, and P = 0.001,
      respectively). The mean values of the immunolabeling intensities of eNOS, nNOS,
      and iNOS in the brain stem were significantly lower in the study group compared
      with the control group (P = 0.001, P = 0.025, and P = 0.005, respectively).
      CONCLUSIONS: In this experimental model of migraine in adolescent rats,
      intracisternal injection of carrageenan was associated with a significant
      increase in the production of NOS enzymes in the brain stem. Pretreatment with
      sumatriptan was associated with a decrease in NOS production.

PMID- 24683225
TI  - Effects of probiotic supplementation on markers of acute pancreatitis in rats.
AB  - BACKGROUND: Intestinal barrier disruption followed by bacterial translocation
      seems to play a role in secondary pancreatic infection in acute pancreatitis. The
      use of probiotics as a possible adjuvant strategy in the treatment of acute
      pancreatitis needs to be investigated. OBJECTIVE: The aim of this study was to
      determine the effects of dietary supplementation with a prophylactically
      administered multispecies probiotic mixture on the markers of acute pancreatitis
      and on the occurrence of bacterial translocation. METHODS: Thirty adult male
      Wistar rats were randomly assigned to 1 of 3 groups of 10 rats each: (1) the PS
      group, in which the rats were given probiotic supplementation prior to induction
      of acute pancreatitis; (2) the WP group, in which the rats underwent surgery to
      induce acute pancreatitis without prior probiotic supplementation; and (3) the
      control group, in which the rats underwent sham surgery. For 14 days before
      surgery, animals in the PS group received a single daily dose containing ~1.2 *
      10(9) colony-forming units of a probiotic mixture administered intragastrically
      as a bolus. On day 15, the animals underwent surgery to induce acute pancreatitis
      (PS and WP groups) or simulated surgery (control group). Blood samples were
      collected to determine leukocyte count, amylase and lipase activities, and
      glucose and calcium concentrations immediately before and 6 and 12 hours after
      the beginning of the procedure. Samples of pancreas, spleen, liver, and
      mesenteric lymph nodes were harvested for microbiologic and histopathologic
      analysis after the last blood sample collection. The pathologist examining the
      histopathology was blinded to treatment assignment. RESULTS: The mean leukocyte
      count was significantly increased in the PS group compared with the WP group (P =
      0.018), whereas the serum amylase and lipase activities and the serum glucose and
      calcium concentrations were not significantly different between the 2 groups.
      Comparing the risk for tissue colonization in the PS group with that of the WP
      group, the odds ratio (OR) for pancreas was 2.91 (95% CI, 0.13-67.10); liver,
      66.55 (95% CI, 1.89-2282.66); spleen, 88.58 (95% CI, 3.04-2583.08); and
      mesenteric lymph nodes, 1.23 (95% CI, 0.06-25.48). When the risks for
      histopathologic changes were compared between the 2 groups, the OR for acinar
      necrosis was 1.73 (95% CI, 0.21-12.17); steatonecrosis, 12.08 (95% CI, 1.26
      115.54); hemorrhage, 1.38 (95% CI, 0.21-9.53); and leukocyte infiltration, 5.91
      (95% CI, 0.64-54.89). CONCLUSION: Probiotic supplementation before the induction
      of acute pancreatitis was associated with a greater degree of bacterial
      translocation and pancreatic tissue damage in this animal model.

PMID- 24683226
TI  - Relationship of serum methotrexate concentration in high-dose methotrexate
      chemotherapy to prognosis and tolerability: A prospective cohort study in chinese
      adults with osteosarcoma.
AB  - BACKGROUND: Cancer that originates in the bone, termed primary bone cancer, is
      rare. Osteosarcoma (OS) occurs primarily in growing bone tissue and is more
      prevalent in children and adolescents. OS in adults is rare, with 3 to 5 cases
      per million population per year worldwide. There are limited data on treatment
      related prognosis and adverse reactions in adults reported in the literature.
      OBJECTIVES: The aims of this study were to investigate factors that influence
      serum methotrexate (MTX) concentrations used in chemotherapy in Chinese adult
      patients with OS, and to determine the correlations (based on age, sex, and
      dosage), if any, between MTX and prognosis, in terms of disease-free survival
      (DFS) and overall survival (OAS), and tolerability. METHODS: Adult patients aged
      >=30 years with OS received >=3 courses (2 courses before surgery and 3-4 courses
      postsurgery) of high-dose MTX (6 or 8 g/m(2)) combined chemotherapy. The regimen
      consisted of day 1: MTX + folinic acid (herein referred to as citrovorum factor
      rescue); day 8: cisplatin; days 21 to 25: ifosfamide + mesna; and day 21:
      doxorubicin. Serum MTX concentrations were assessed immediately after the end of
      infusion (baseline) and at 24 and 48 hours using high-performance liquid
      chromatography. Changes in serum MTX concentrations, factors that influence serum
      MTX concentrations, and the relationship between serum MTX concentrations and
      prognosis and tolerability (determined by adverse reactions) were analyzed.
      Patients received a second course of treatment after a 3-week period. RESULTS:
      Ninety patients (58 men, 32 women; age range, 30-67 years) with OS were included
      in the study. A total of 532 courses of combined chemotherapy were administered.
      The serum MTX concentrations ranged widely at baseline (244.31-929.68 mol/L, Cmin
      and Cmax, respectively) and at 24 hours (0.73-28.24 mol/L, respectively),
      suggesting that the serum MTX concentrations varied significantly between
      different individuals and within the same individual at different time points.
      The serum MTX concentrations in ~23% of cases (122/532) determined at 24 and/or
      48 hours were numerically higher than the safety values (according to Nirenberg's
      reference: irreversible damage if MTX concentration was >10 umol/L and > 1 umol/L
      at 24 and 48 hours, respectively). No correlation was found between high serum
      MTX concentration at baseline and high serum MTX concentration at 24 hours (r =
      0.401). The prevalences of the 3 most common adverse reactions in these patients
      were depressed white blood cell count (44.03%), dental ulcer (23.0%), and rash
      (18.0%). However, in the remaining 410 courses in which serum MTX concentrations
      were lower than the safety values, these prevalences were 14.6%, 3-9%, and 2.4%,
      respectively. Neither age nor sex was significantly associated with MTX Cmax, but
      dosage was (P < 0.05). Patients with a serum MTX Cmax concentration >500 MUmol/L
      at baseline had a significantly longer DFS rate than those with <=500 umol/L (P =
      0.040). There were no significant between-group differences in the OAS rates.
      conclusions: In these Chinese patients with OS, serum MTX concentrations measured
      at different time points were varied. The findings suggest that adverse reactions
      occurred in patients whose serum MTX concentrations at 24 and/or 48 hours were
      higher than the safety values. The dosage appeared to have influenced MTX Cmax,
      while sex and age did not, and the Cmax was significantly related to DFS but not
      OAS.

PMID- 24683227
TI  - Long-term pamidronate treatment of polyostotic fibrous dysplasia of bone: A case
      series in young adults.
AB  - BACKGROUND: Limited information is available about long-term pamidronate
      treatment in adults with fibrous dysplasia (FD) of bone. OBJECTIVE: The aim of
      this case series was to report the clinical outcomes and the biochemical and
      densitometric findings in a group of young adult patients with polyostotic FD
      treated for >=3 years with IV pamidronate. METHODS: Pamidronate was administered
      every 6 months (60 mg/d for 3 days) for 2 years. Thereafter, treatment was
      individualized. Pamidronate was administered at shorter or longer intervals based
      on response. Bone pain, radiography, serum bone alkaline phosphatase (BALP)
      activity, and urinary C-terminal cross-linking telopep-tide of type I collagen
      (CTX-I) concentration were assessed for a mean of 7 years. Bone mineral density
      (BMD) of FD areas (FDas) and contralateral areas (CLas) were measured at baseline
      and at 12 and 24 months. Data were collected prospectively. RESULTS: Seven
      patients (5 women, 2 men; mean [SD] age, 31.0 [7.2] years [range, 22-43 years])
      were included in the study. Patients received IV pamidronate for a mean of 6.9
      years (median, 7.1 years [range, 3.7-10.9 years]). Pamidronate was associated
      with a reduction in bone pain and a significant reduction in BALP in all patients
      at the end of follow-up (P < 0.02). The mean reduction from baseline in CTX-I
      concentration (measured in 3 patients) was 56%; this difference was not
      significant. Mean BMD values of FDas were significantly increased at 12 months
      (by 5.9%; P < 0.05) compared with baseline; but was not significantly increased
      at 24 months (7.3%), probably reflecting a higher dispersion of values due to
      individual responses to treatment. No significant changes were observed in CLa
      BMDs. Mean BMD of FDa had a numerically lower decrease of 15.3% compared with CLa
      at baseline; these decreases with pamidronate were 10.8% at 12 months (P = NS)
      and 9.3% at 24 months (P < 0.05). Refilling of osteolytic lesions was not
      observed. CONCLUSIONS: These patients with FD of bone treated with IV pamidronate
      long term had improvement in bone pain and BMD. The effectiveness of
      individualized pamidronate administration in the long-term treatment of FD in
      adult patients should be investigated in blinded controlled trials.

PMID- 24683228
TI  - Aripiprazole in the treatment of early-onset schizophrenia spectrum disorder: A
      case series in Korean children and adolescents.
AB  - OBJECTIVE: The aim of this case series was to assess the effectiveness and tol
      erability of aripiprazole in Korean children and adolescents with early-onset
      schizophrenia spectrum (EOSS) disorder. METHODS: The medical records of
      aripiprazole-treated patients with EOSS were retrospectively reviewed. Changes in
      illness severity were measured using the Clinical Global Impression-Severity of
      Illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales.
      RESULTS: Data from 22 children and adolescents were included (12 girls, 10 boys;
      mean [SD] age, 14.0 [2.4] years). The mean (SD) dosage of aripiprazole was 19.8
      (9.4) mg/d (median, 18.7 mg/d; mode, 15, 30 mg/d), and the range of treatment
      duration was 21 to 838 days. Mean (SD) CGI-S score improved significantly from
      baseline to end point (from 5.7 [0.7] to 4.3 [1.4]; P < 0.001). Based on changes
      in chart-extracted CGI-I scores, significantly greater improvement was associated
      with negative symptoms compared with positive symptoms (U = 25.5; P = 0.028; r = 
      0.47). Aripiprazole was discontinued due to insufficient effect in 5 patients
      (22.7%) and treatment-emergent adverse events in 3 patients (13.6%). CONCLUSION:
      The results from this small study suggest that aripiprazole was moderately
      effective in reducing psychotic symptoms in these Korean children and adolescents
      with EOSS.

PMID- 24683229
TI  - The efficacy and tolerability of glucosamine sulfate in the treatment of knee
      osteoarthritis: A randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis and is often
      associated with disability and impaired quality of life. OBJECTIVE: The aim of
      the study was to assess the efficacy and tolerability of glucosamine sulfate (GS)
      in the treatment of knee OA. METHODS: Consecutive outpatients affected by primary
      monolateral or bilateral knee OA were enrolled in this double-blind, double
      dummy, prospective, randomized, placebo-controlled trial. One group received GS
      1500 mg QD for 12 weeks, and the other group received placebo QD for 12 weeks.
      The treatment period was followed by a 12-week treatment-free observation phase.
      Each patient was examined at baseline and at weeks 4, 8, 12, 16, 20, and 24. The
      primary efficacy criteria were pain at rest and during movement, assessed on a
      visual analog scale (VAS) of 0 to 100 mm. The secondary criteria included the
      Western Ontario and McMaster Universities (WOMAC) index for total pain score (W
      TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS).
      VAS, W-TPS, W-TSS, and W-TPFS were evaluated at baseline and at weeks 4, 8, 12,
      16, 20, and 24. Analgesic drug consumption (ie, acetaminophen or NSAIDs) was also
      assessed. RESULTS: Patient demographics were similar in the GS and placebo
      groups. Of 60 randomized patients (30 per group), 56 completed the study (28
      treated with GS and 28 who received placebo). Statistically significant
      improvements in symptomatic knee OA were observed, as measured by differences in
      resting pain at weeks 8, 12, and 16 (all, P < 0.05 vs placebo) and in pain during
      movement at weeks 12 and 16 (both, P < 0.05). W-TPS was lower with GS than
      placebo at weeks 8, 12, and 16 (all, P < 0.01), and at week 20 (P < 0.05). W-TSS
      was also lower with GS than placebo at weeks 8, 12, 16, and 20 (all, P < 0.05). W
      TPFS was lower with GS than placebo at weeks 8 (P < 0.05), 12 (P < 0.01), 16 (P <
      0.05), and 20 (P < 0.05). Drug consumption was lower in the GS group than the
      placebo group at weeks 8, 12, 16, and 20 (all, P < 0.05). The incidence of
      adverse events was 36.7% with GS and 40.0% with placebo. CONCLUSIONS: GS 1500 mg
      QD PO for 12 weeks was associated with statistically significant reductions in
      pain and improvements in functioning, with decreased analgesic consumption,
      compared with baseline and placebo in these patients with knee OA. A carryover
      effect was detected after treatment ended.

PMID- 24683230
TI  - Controlled hypotension with desflurane combined with esmolol or dexmedetomidine
      during tympanoplasty in adults: A double-blind, randomized, controlled trial.
AB  - BACKGROUND: Controlled hypotension is a technique that is used to limit
      intraoperative blood loss to provide the best possible surgical field during
      surgery. OBJECTIVE: The aim of this double-blind, randomized, controlled study
      was to compare the effects of desflurane combined with esmolol or dexmedetomidine
      on the amount of blood in the surgical field, recovery time, and tolerability in
      adult patients undergoing tympanoplasty. METHODS: Turkish patients aged 18 to 60
      years, classified as American Society of Anesthesiologists physical status I or
      II, who were scheduled for tympanoplasty were randomly divided into 2 groups: the
      esmolol group or the dexmedetomidine group. After the anesthesia induction in the
      esmolol group, a loading dose of esmolol was infused intravenously over 1 minute
      at 1 mg/kg, followed by a maintenance rate of 0.4 to 0.8 mg/ kg/h. In the
      dexmedetomidine group, a loading dose of dexmedetomidine was infused
      intravenously over 10 minutes at a rate of 1 MUg/kg, followed by a maintenance
      rate of 0.4 to 0.8 MUg/kg/h. The infusion rates were then titrated to maintain
      mean arterial pressure (MAP) of 65 to 75 mm Hg. General anesthesia was maintained
      with desflurane 4% to 6%. Heart rate (HR) and MAP were recorded during
      anesthesia. The following 6-point scale was used to assess the amount of bleeding
      in the operative field: 0 = no bleeding, a virtually bloodless field; 1 =
      bleeding that was so mild that it was not a surgical nuisance; 2 = moderate
      bleeding that was a nuisance but did not interfere with accurate dissection; 3 =
      moderate bleeding that moderately compromised surgical dissection; 4 = bleeding
      that was heavy but controllable and that significantly interfered with surgical
      dissection; and 5 = massive bleeding that was uncontrollable and made dissection
      impossible. Scores <=2 were considered to be optimal surgical conditions. The
      sedation score was determined at 15, 30, and 60 minutes after tracheal extubation
      using the following scale: 1 = anxious, agitated, or restless; 2 = cooperative,
      oriented, and tranquil; 3 = responsive to commands; 4 = asleep, but with brisk
      response to light, glabellar tap, or loud auditory stimulus; 5 = asleep, sluggish
      response to glabellar tap or auditory stimulus; and 6 = asleep, no response. Time
      to extubation and to total recovery from anesthesia (Aldrete score >=9 on a scale
      of 0-10), adverse effects (eg, intraoperative hypotension [blood pressure <65 mm
      Hg], bradycardia [HR <50 beats/min]), intraoperative fentanyl consumption, and
      postoperative nausea and vomiting were recorded. Arterial blood gas analysis and
      kidney and liver function tests were conducted. All patients were evaluated by
      the same attending surgeon and anesthesiologist, both of whom were blinded to the
      administered study drugs. RESULTS: Fifty-two consecutive white patients
      undergoing tympanoplasty were identified. Two patients had to be excluded because
      of hypertension and 2 refused to participate. Forty-eight patients were equally
      randomized to either the esmolol group (n = 24 [16 women, 8 men]; mean [SD] age,
      38.4 [10.5] years) or the dexmedetomi-dine group (n = 24 [17 women, 7 men]; mean
      age, 35.5 [14.7] years). Sedation scores were not collected for 1 patient in the
      esmolol group; therefore, analysis was conducted for 23 patients. The median
      (range) of the scores for the amount of blood in the surgical field in the
      esmolol and dexmedetomidine groups was 1 (0-3) and 1 (0-2), respectively (P =
      NS). Mean intraoperative fentanyl consumption in the esmolol group was
      significantly higher than in the dexmedetomidine group (50.0 [3.0] vs 25.0 [2.5]
      MUg/min; P = 0.002). In the esmolol group, the mean times to extubation and to
      recovery from anesthesia were significantly shorter than those of the
      dexmedetomidine group (7.0 [1.4] vs 9.1 [1.9] minutes, respectively; 5.9 [2.1] vs
      7.9 [2.3] minutes; both, P = 0.001). The mean sedation scores were significantly
      lower in the esmolol group (n = 23, because of intent-to-treat analysis) compared
      with the dexmedetomidine group at 15 minutes (2.5 [0.6] vs 3.6 [0.5]; P = 0.001)
      and 30 minutes (2.6 [0.6] vs 3.3 [0.6]; P = 0.001) postoperatively. No
      significant differences were found between the study groups in regard to blood
      urea nitrogen or creatinine concentration, aspartate aminotransferase or alanine
      aminotransferase activities, pH, partial pressure of carbon dioxide, or
      bicarbonate, before or after the operation. CONCLUSIONS: Both esmolol and
      dexmedetomidine, combined with desflurane, provided an effective and well
      tolerated method of achieving controlled hypotension to limit the amount of blood
      in the surgical field in these adult patients undergoing tympanoplasty. Esmolol
      was associated with significantly shorter extubation and recovery times and
      significantly less postoperative sedation compared with dexmedetomidine.

PMID- 24683232
TI  - Changes in visual acuity, axial length, and refraction after removal of
      intraocular silicone oil following retinal reattachment surgery in Chinese
      patients: An open-label, prospective study.
AB  - BACKGROUND: As a vitreous substitute for long-term tamponade, silicone oil is
      widely used in vitreoretinal surgery to treat retinal detachment with
      proliferative vitreoretinopathy and some internal reconstruction after globe
      trauma. OBJECTIVES: The aim of this study was to compare the changes in visual
      acuity, axial length, and refraction in eyes before and after removal of
      intraocular silicone oil of 2 different viscosities after retinal reattachment
      surgery. The difference in the final anatomic success (stable retinal
      reattachment) rate was also assessed. METHODS: Patients with surgically
      reattached retinas were enrolled in this open-label, prospective, nonrandomized
      study. All patients underwent pars plana vitrecto-my, lensectomy, scleral
      buckling or encircling, and epiretinal membrane dissection; silicone oil was
      removed after stable retinal reattachment was achieved. Refraction, axial length,
      final visual acuity, and stable retinal reattachment were assessed <=2 days prior
      to surgery (baseline) and <=1 month after silicone oil removal. Refraction was
      measured using an autorefractometer, and axial length was measured using A-scan
      ultrasonography, while visual acuity was assessed using a standard Snellen chart.
      RESULTS: Of the 96 eyes assessed for inclusion, 89 eyes of 89 Chinese patients
      (mean [SD] age, 36.8 [4.3] years) were included in the study. Forty-two eyes
      (47.2%) were filled with 3700-centistoke (cS) silicone oil and 47 (52.8%) were
      filled with 5000-cS silicone oil. The mean interval between instillation and
      removal of the silicone oil was similar between the 3700-cS and 5000-cS groups
      (5.37 vs 5.10 months, respectively). The mean changes in visual acuity from
      before surgery to after removal of the silicone oil in the 3700-cS and 5000-cS
      groups were not significantly different (13/100 vs 15/100). The mean increase in
      axial length was also not significantly different in the 3700-cS group compared
      with the 5000-cS group (11.92 [1.97] vs 12.33 [1.28] mm). Mean decrease in
      refraction was significantly lower in the 3700-cS group compared with the 5000-cS
      group (5.80 [1.51] vs 6.88 [2.31] diopters; t = 2.57, P < 0.05). The anatomic
      success rate was 92.9% (39/42 patients) in the 3700-cS group and 91.5% (43/47) in
      the 5000-cS group. CONCLUSIONS: A statistically significant decrease in
      refraction from baseline was found in the 3700-cS group compared with the 5000-cS
      group in these Chinese patients who underwent instillation and removal of
      silicone oil after retinal reattachment surgery. There were no other
      statistically significant differences between the 2 groups.

PMID- 24683231
TI  - Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes
      and hemodynamic responses to tracheal extubation during rhinoplasty: A double
      blind, randomized, controlled study.
AB  - BACKGROUND: Stimulation of various sites, from the nasal mucosa to the diaphragm,
      can evoke laryngospasm. To reduce airway reflexes, tracheal extubation should be
      performed while the patient is deeply anesthetized or with drugs that do not
      depress ventilation. However, tracheal extubation during rhinoplasty may be
      difficult because of the aspiration of blood and the possibility of laryngospasm.
      Dexmedetomidine and fentanyl both have sedative and analgesic effects, but
      dexmedetomidine has been reported to induce sedation without affecting
      respiratory status. OBJECTIVE: The aim of this study was to compare the effects
      of dexmedetomidine and fentanyl on airway reflexes and hemodynamic responses to
      tracheal extubation in patients undergoing rhinoplasty. METHODS: This double
      blind, randomized, controlled study was conducted at the Erciyes University
      Medical Center, Kayseri, Turkey. Patients classified as American Society of
      Anesthesiologists physical status I or II who were undergoing elective
      rhinoplasty between January 2007 and June 2007 with general anesthesia were
      eligible for study entry. Using a sealed-envelope method, the patients were
      randomly divided into 2 groups (20 patients per group). Five minutes before
      extubation, patients received either dexmedetomidine 0.5 MUg/kg in 100 mL of
      isotonic saline or fentanyl 1 MUg/kg in 100 mL of isotonic saline intravenously.
      All patients were extubated by anesthesiologists who were blinded to the study
      drugs, and all were continuously monitored for 15 minutes after extubation. Heart
      rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and
      oxygen saturation using pulse oximetry (SpO2) were recorded before anesthesia,
      after drug administration, after skin incision, at the completion of surgery, and
      1, 5, and 10 minutes before and after tracheal extubation. Any prevalence of
      laryngospasm, bronchospasm, or desaturation was recorded. RESULTS: Forty patients
      (25 men, 15 women; mean [SD] age, 24.86 [7.43] years) were included in the study.
      Dexmedetomidine was associated with a significant increase in extubation quality
      compared with fentanyl, reflected in the prevalence of cough after extubation
      (85% [17/20] vs 30% [6/20] of patients, respectively; P = 0.001). There were no
      clinically significant decreases in HR, SBP, DBP, or SpO2 after extubation with
      dexmedetomidine or fentanyl. In the dexmedetomidine group, HR was not
      significantly increased after extubation; however, in the fentanyl group, HR was
      significantly increased compared with the preextubation values (all, P = 0.007).
      HR was significantly higher in the fentanyl group compared with the
      dexmedetomidine group at 1, 5, and 10 minutes after extubation (all, P = 0.003).
      Compared with preextubation values, SBP was significantly increased at 1 and 5
      minutes after extubation in the dexmedetomidine group (both, P = 0.033) and at 1,
      5, and 10 minutes after extubation in the fentanyl group (all, P = 0.033). The
      postoperative sedation scores and the extubation, awakening, and orientation
      times were not significantly different between the 2 groups. In the
      dexmedetomidine group, bradycardia (HR <45 beats/min) was observed in 2 patients
      and emesis was observed in 2 patients. In the fentanyl group, emesis was observed
      in 3 patients, bradycardia in 2 patients, vomiting in 1 patient, and shivering in
      1 patient; vertigo was reported in 1 patient. There were no significant
      differences in the prevalence of adverse events between the 2 groups. CONCLUSION:
      The findings in the present study suggest that dexmedetomidine 0.5 MUg/kg IV,
      administered before extubation, was more effective in attenuating airway reflex
      responses to tracheal extubation and maintaining hemodynamic stability without
      prolonging recovery compared with fentanyl 1 MUg/kg IV in these patients
      undergoing rhinoplasty.

PMID- 24683233
TI  - Pharmacokinetic properties of lansoprazole (30-mg enteric-coated capsules) and
      its metabolites: A single-dose, open-label study in healthy Chinese male
      subjects.
AB  - BACKGROUND: Lansoprazole, a benzimidazole derivative, is indicated for the
      treatment of various peptic diseases. It is metabolized mainly in the liver, and
      its primary active metabolites present in plasma are 5'-hydroxy lansoprazole and
      lansoprazole sulfone. Few data are available on the pharmacokinetic properties of
      lansoprazole, 5'-hydroxy lansoprazole, and lansoprazole sulfone, which can be
      used to measure cytochrome P450 (CYP) 2C19 activity. OBJECTIVES: The aims of this
      study were to investigate the clinical plasma pharmacokinetic properties of
      lansoprazole and its metabolites in healthy Chinese male volunteers, and to
      assess the influences of CYP2C19 on the pharmacokinetics of lansoprazole.
      METHODS: Healthy adult Chinese male volunteers were enrolled in this single-dose,
      open-label study. All patients received a single oral enteric capsule containing
      30 mg of lansoprazole after a 12-hour overnight fast. Serial blood samples were
      collected immediately before (0 hour) and at 20, 40, 60, 90, 120, and 150 minutes
      and 3, 4, 6, 8, 10, 12, 15, and 24 hours after study drug administration. The
      plasma concentrations of lansoprazole, 5'-hydroxy lansoprazole, and lansoprazole
      sulfone were determined using a validated internal standard high-performance
      liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.
      Pharmacokinetic properties (including Cmax, Tmax, elimination t1/2 [t1/2z], mean
      residence time [MRT], AUC0-24, AUC0-infinity, apparent oral clearance [CLz/F],
      and apparent volume of distribution [Vz/F]) were determined using the
      noncompartmental method. RESULTS: Twenty volunteers (mean [SD] age, 34.9 [2.9]
      years; weight, 64.6 [2.2] kg; height, 171.3 [3.3] cm) were enrolled in and
      completed the study. The mean (SD) pharmacokinetic properties of lansoprazole
      were as follows: Cmax, 1047 (344) ng/mL; Tmax, 2.0 (0.7) hours; t1/2z, 2.24
      (1.43) hours; MRT, 3.62 (0.87) hours; AUC0-24, 3388 (1484) ng/mL/h; AUC0
      infinity, 3496 (1693) ng/mL/h; CLz/F, 9.96 (3.74) L/h; and Vz/F, 32.83 (11.74) L.
      The findings with 5'-hydroxy lansoprazole and lansoprazole sulfone, respectively,
      were as follows: Cmax, 111.2 (41.8) and 66.6 (52.9) ng/mL; Tmax, 2.1 (0.8) and
      1.9 (0.8) hours; t1/2z, 2.31 (1.18) and 2.52 (1.54) hours; and AUC0-24, 317.0
      (81.2) and 231.9 (241.7) ng/mL/h. No adverse events were reported throughout the
      study. CONCLUSIONS: In these healthy Chinese male volunteers administered a
      single oral dose of lansoprazole 30 mg, absorption of lansoprazole was rapid
      (mean Cmax, 1047 ng/mL; Tmax, ~2.0 hours). Its 2 primary active metabolites, 5'
      hydroxy lansoprazole and lansoprazole sulfone, were identified in measurable
      quantities in plasma (Cmax, 111.2 and 66.6 ng/mL, respectively; and Tmax, 2.1 and
      1.9 hours). The plasma t1/2z did not appear to reflect the duration of
      suppression of gastric acid secretion: the t1/2z values of lansoprazole and the 2
      metabolites were ~2 to 2.5 hours, while the acid-inhibitory effect lasted >24
      hours. Cmax, AUC, and t1/2z of lansoprazole, and especially lansoprazole sulfone,
      varied. Differences in metabolism types and/or genotype of CYP2C19 should be
      taken into account when planning a lansoprazole dosing regimen.

PMID- 24683234
TI  - Treatment of recurrent retinal angiomatous proliferation with intravitreal
      triamcinolone acetonide followed by photodynamic therapy with verteporfin: A
      retrospective case series.
AB  - OBJECTIVE: The aim of this study was to report the effect on tolerability of
      combined treatment with intravitreal triamcinolone acetonide (IVT) and
      photodynamic therapy (PDT) with verteporfin in patients with stage II retinal
      angiomatous proliferation (RAP) who had been treated previously with PDT and
      presented with recurrent RAP (R-RAP). METHODS: This was a retrospective case
      series of patients with R-RAP after PDT (1-5 treatments) treated once with IVT
      followed 1 month later by PDT. A visual acuity test, fluorescein and indocyanine
      green angiography, and optical coherence tomography were performed at baseline
      and at 1, 3, and 6 months. RESULTS: Five patients (4 men, 1 woman; mean [SD] age,
      76.8 [3.9] years) with 6 eyes diagnosed with stage II R-RAP who had previously
      been treated with PDT and who received an IVT injection and PDT within 1 month
      were included in the study. Best corrected visual acuity (BCVA) remained stable
      after IVT in 5 eyes (83%) and deteriorated in 1 eye (17%). After PDT, BCVA
      remained stable in 2 eyes (33%) and deteriorated in 4 eyes (67%). IVT treatment
      combined with PDT also reduced fluorescein leakage. Median lesion size increased
      24% before PDT and 61% at 6 months after PDT. One eye had intraocular
      hypertension at 3 months, and 1 eye developed a pigment epithelial tear after
      PDT. CONCLUSION: The results were limited by the number of eyes and relatively
      short follow-up, but in this study, PDT after IVT did not appear to be as
      effective or well tolerated in 5 patients who had already been treated with PDT
      and presented with R-RAP.

PMID- 24683235
TI  - Adjuvant treatments for Henoch-Schonlein purpura nephritis in children: A
      systematic review.
AB  - BACKGROUND: The management of Henoch-Schonlein purpura nephritis (HSPN) in
      childhood is controversial. Adjuvant therapies such as immunoglobulin,
      anticoagulants, and vitamins have been used with conventional treatments despite
      a lack of evidence of their efficacy. OBJECTIVE: The aim of this study was to
      review the scientific literature regarding adjuvant treatments administered with
      conventional drugs in the treatment of childhood HSPN. METHODS: Published
      articles were identified from the MEDLINE and EMBASE databases (1988-December
      2008; key words: Henoch-Schonlein nephritis and Henoch-Schonlein purpura). The
      search was limited to published English-language studies on therapeutic options
      for HSPN in children. RESULTS: A total of 12 studies were identified and included
      in this review; most (n = 8) were case series or retrospective studies. Studies
      of conventional therapy combined with adjuvant treatment should be interpreted
      with caution. In particular, factor XIII administration was reported to improve
      kidney symptoms in 1 study. Based on the results from 9 studies, no convincing
      evidence on intravenous immunoglobu-lin, urokinase, or anticoagulants was
      identified. No substantial information was available on the benefit of
      antiplatelet agents or heparin in treating HSPN. Integrating treatment with
      vitamin E was not recommended based on the results from 1 randomized controlled
      trial. Fish oil was reported to be effective in 1 case series. CONCLUSIONS:
      Studies concerning the treatment of HSPN in children with adjuvant therapies were
      retrospective and recommendations were drawn from level IV evidence. One
      randomized controlled trial on the use of tocopherol as adjuvant treatment was
      identified; however, no clinical utility was reported. At present, there is no
      strong evidence supporting benefits with the use of adjuvant treatments.

PMID- 24683236
TI  - Use of adjunctive mitomycin C in external dacryocystorhinostomy surgery compared
      with surgery alone in patients with nasolacrimal duct obstruction: A prospective,
      double-masked, randomized, controlled trial.
AB  - BACKGROUND: The most common cause for the failure of external
      dacryocystorhinostomy (DCR) surgery is the formation of granulation tissue at the
      osteotomy site or common canaliculus. OBJECTIVES: The aims of this study were to
      assess the efficacy of intraoperative adjunctive mitomycin C (MMC) treatment in
      external DCR surgery and to compare this procedure with the standard DCR
      procedure alone in the long term (1 year). METHODS: In this prospective, double
      masked, randomized, controlled trial, patients with primary acquired nasolacrimal
      duct obstruction were randomized (using a random number table) into 2 groups
      based on surgical procedure. In the MMC group, intraoperative adjunctive MMC 0.2
      mg/mL was applied to the osteotomy site for 30 minutes. The control group
      underwent standard DCR procedure only. The results of the DCR surgeries were
      assessed using objective findings (eg, cessation of excessive tearing via
      nasolacrimal duct irrigation and the improvement in height of tear meniscus) and
      subjective symptoms (asking patients to describe the degree of tearing
      improvement). Both the patients and the researchers who were assessing the study
      outcomes were masked to treatment group. RESULTS: One hundred eyes of 100 Turkish
      patients were assessed and equally randomized to the MMC (27 women, 23 men; mean
      [SD] age, 47.0 [7.6] years) and control (26 women, 24 men; mean age, 46.6 [8.8]
      years) groups. The follow-up period was not significantly different between the
      MMC and the control groups (13.1 [1.1] vs 13.2 [1.4] months). Significantly more
      eyes in the MMC group than the control group remained symptom-free throughout the
      1-year follow-up period (45/50 [90%] vs 33/50 [66%]; P=0.005). Significantly more
      patients in the control group than the MMC group had an improvement in symptoms
      at the 1-year follow-up (8/50 [16%] vs 2/50 [4%] eyes; P=0.005). Based on the
      patency of the drainage system, the success rate was significantly greater in the
      MMC group than the control group (48/50 [96%] vs 42/50 [84%]; P=0.005). Based on
      nasolacrimal duct irrigation, significantly fewer patients in the MMC group than
      the control group had an enclosed naso-lacrimal duct (2/50 [4%] vs 8/50 [16%]).
      No adverse effects (eg, abnormal nasal bleeding, mucosal necrosis, infection) or
      any other surgical adverse events were observed. CONCLUSIONS: In the management
      of these patients with primary acquired nasolacrimal duct obstruction, adjunctive
      intraoperative MMC application with standard DCR surgery had a significantly
      higher success rate than did standard DCR surgery alone. Further large, double
      masked, randomized studies are needed to confirm these findings.

PMID- 24683237
TI  - Comparison of mitomycin C and limbal-conjunctival autograft in the prevention of
      pterygial recurrence in Turkish patients: A one-year, randomized, assessor
      masked, controlled trial.
AB  - BACKGROUND: A pterygium is a fibrovascular overgrowth of degenerative bulbar
      conjunctival tissue that grows over the limbus onto the cornea. Although various
      approaches have been proposed for the treatment of pterygium, the common problem
      after these treatments is recurrence. OBJECTIVES: The goals of this study were to
      compare the efficacy of mitomycin C (MMC) and limbal-conjunctival autograft
      (LCAU) in preventing recurrence of primary pterygia and to monitor long-term
      adverse effects (AEs). METHODS: Patients undergoing pterygium surgery between
      February 2006 and May 2007 were assessed prospectively and randomly divided into
      2 groups using a random number table. The MMC group underwent pterygium excision
      and received 0.02% MMC intraoperatively for 2 minutes. The LCAU group underwent
      pterygium excision and LCAU. Recurrence and AE rates of the 2 treatments were
      compared during the 1-year follow-up period. Assessors for pterygial recurrence
      were masked to treatment group. RESULTS: One hundred thirteen eyes (57 patients
      in the MMC group and 56 patients in the LCAU group) were included in the study.
      Thirteen of the patients (7 in the MMC group and 6 in the LCAU group) were
      withdrawn due to irregular attendance at follow-up visits or lack of sufficient
      dose and duration for postoperative topical antibiotic and steroid
      administration; their data were excluded from analysis. Fifty patients (MMC
      group: 26 men, 24 women; mean [SD] age, 48.0 [12.3] years; age range, 30-73
      years; LCAU group: 27 men, 23 women; mean age, 49.0 [12.6] years; age range, 28
      71 years) in each group completed the study. The mean (SD) length of the
      pterygium across the limbus was similar in the MMC group and the LCAU group (4.18
      [1.27] vs 4.07 [1.24] mm). The mean follow-up period was also similar in the 2
      groups (16.0 [1.9] vs 15.0 [1.7] months). The rate of recurrence was
      significantly greater in the MMC group than in the LCAU group (10 [20.0%] vs 2
      [4.0%] patients; P=0.035). Seven patients (14.0%) in the MMC group experienced
      AEs: conjunctival cyst (3 patients), symblepharon (2), conjunctival granuloma
      (1), and dellen (1). In the LCAU group, 1 patient (2.0%; P=0.032 vs MMC group)
      experienced permanent graft edema. All patients in the LCAU group experienced
      transient graft edema, with recovery occurring in 3 to 4 weeks. There were no
      intraoperative complications and there was no graft rejection. CONCLUSIONS:
      Recurrence and postoperative AEs were less frequently observed in primary
      excision with LCAU than with MMC in these Turkish patients who completed the
      study. This study found that pterygium excision with LCAU was well tolerated and
      effective in these patients.

PMID- 24683238
TI  - Therapeutic management of uncomplicated gastroesophageal reflux disease in france
      in 2005: Potential cost savings of omeprazole substitution.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) cost the French health care system >?1
      billion in 2005, and ~50% of PPI prescriptions were for the treatment of
      gastroesophageal reflux disease (GERD). OBJECTIVES: This study aimed to describe
      the current use of PPIs for GERD, to estimate the total annual costs of
      treatment, and to evaluate the economic impact of the various possible
      substitutions among PPIs available for this indication in France. METHODS: Data
      from a sample of patients aged >=20 years who visited their general practitioner
      (GP) at least once in 2005 for uncomplicated, symptomatic GERD were retrieved
      from the Thales database (a group of 1200 representative GPs connected to a
      computerized network). Costs of the prescriptions presented for reimbursement and
      costs of those reimbursed by the French health care insurance system were
      analyzed. We then evaluated the economic consequences of replacing full-dose
      generic omeprazole (after substitution from brand-name omeprazole by the
      pharmacists) with other compounds that are indicated for mild symptoms at half
      dose (ie, lansoprazole 15 mg, pantoprazole 20 mg, rabeprazole 10 mg, and
      esomeprazole 20 mg). The results were adjusted to account for the proportions of
      patients who had full health care coverage and the treatment duration as reported
      in the database. RESULTS are presented from the perspective of the French health
      care insurance system. RESULTS: In 2005, a total of 122,571 patients (mean age,
      55.7 years; 45.5% men; 13.8% with a history of at least 1 gastrointestinal
      disorder) met the inclusion criteria. Extrapolated to the French population, this
      sample corresponded to ~5.7 million people (ie, 13% of the adult population who
      visited a GP during the year). PPIs were prescribed as first-line treatment for
      GERD in 84.1% of the consultations (14.3% in association with other antiulcer
      drugs). Omeprazole, as a proprietary or generic drug, was prescribed most often
      (78.9%) and at full dose (20 mg), while other compounds (lansoprazole,
      pantoprazole, rabeprazole, and esomeprazole) were prescribed at half dose in
      64.3% of cases. The extrapolated annual cost of PPIs reimbursed for this
      indication was ?465.02 million at a mean reimbursement level of 72.7%. Brand-name
      omeprazole still accounted for ~11% of the total cost reimbursed. Complete
      replacement of brand-name omeprazole with its generic counterpart would have
      reduced costs by ?18.35 million (a decrease of 4.3% in the total reimbursed
      expenditure). The switch from generic full-dose omeprazole to a half dose of
      other PPIs would have allowed further savings ranging from ?2.59 million (with
      lansoprazole) to ?13.19 million (with pantoprazole). CONCLUSION: In accordance
      with recent recommendations for the treatment of uncomplicated GERD and based on
      the 2006 PPI pricing, switching from branded full-dose omeprazole to generic
      omeprazole or to the use of half doses of other PPIs may allow cost savings in
      France.

PMID- 24683240
TI  - Transient neurologic syndrome after spinal anesthesia with epidural steroid
      treatment.
AB  - BACKGROUND: Transient neurologic syndrome (TNS) is a rare complication of spinal
      and epidural anesthesia. It is defined as paradoxic postoperative back pain
      radiating to the lower extremities with no neurologic deficits. Because it is a
      self-limited disease, the treatment is usually symptomatic and consists of NSAIDs
      and injections of a neuromuscular-blocking drug at the trigger points. The
      syndrome may be resistant to this treatment regimen and may last for several
      months, resulting in a long convalescence. CASE SUMMARY: A 63-year-old Turkish
      woman (height, 165 cm; weight, 71 kg) underwent hemorrhoidectomy in the jackknife
      position using spinal anesthesia. No adverse events occurred during puncture or
      surgery or in the immediate postoperative recovery period. Recovery from the
      sensory and motor block was normal. Twenty-four hours after surgery, lower limb
      and plantar pain developed with no sensory or motor deficit. Neurologic
      examination revealed normal motor and sensory function. Electroneuromyography
      showed partial denervation potential of muscles innervated by the left sciatic
      nerve. The symptoms were suggestive of TNS. Combination oral NSAID treatment with
      amitriptyline (25 mg/d) and gabapentin (1200 mg/d) was initiated. Because the
      pain still persisted 6 weeks after surgery, epidural steroid injection with
      triamcinolone acetate (80 mg) with isotonic saline was administered, resulting in
      definite pain relief (visual analog scale score = 0). CONCLUSIONS: Epidural
      steroid treatment was effective in this patient with TNS resistant to treatment
      with NSAIDs, amitriptyline, and gabapentin. Future studies are needed to evaluate
      this treatment.

PMID- 24683239
TI  - Effects of sulfasalazine on lipid peroxidation and histologic liver damage in a
      rat model of obstructive jaundice and obstructive jaundice with
      lipopolysaccharide-induced sepsis.
AB  - BACKGROUND: Sulfasalazine, an inhibitor of cyclooxygenase, 5-lipoxygenase, and
      nuclear factor kappaB (NF-kappaB), has been found to alleviate oxidative damage,
      proinflammatory cytokine production, bile-duct proliferation, neutrophil
      infiltration, and fibrosis. Therefore, it may have a potential effect in
      attenuating lipid peroxidation and histologic liver damage in patients with
      biliary obstruction and biliary obstruction with sepsis. OBJECTIVE: The aim of
      this study was to investigate the effect of sulfasalazine on lipid peroxidation
      and histologic liver damage due to obstructive jaundice (OJ) and to OJ with
      lipopolysaccharide (LPS)-induced sepsis in an experimental model. METHODS: Male
      Wistar rats, weighing 150 to 220 g, were randomized into 6 groups: OJ; OJ + LPS;
      OJ + sulfasalazine; OJ + sulfasalazine + LPS (sulfasalazine administered before
      sepsis); OJ + LPS + sulfasalazine (sulfasalazine administered after sepsis); and
      sham. Liver malondialdehyde (MDA) and myeloperoxidase (MPO) activities were
      assessed to monitor lipid peroxidation and neutrophil infiltration in liver
      tissue. Histologic liver damage was evaluated with hematoxylin-eosin stained
      slides. Liver tissue NF-kappaB and caspase-3 expression were studied
      immunohistopathologically to evaluate lipid peroxidation, liver damage, and
      hepatocyte apoptosis. RESULTS: Forty-eight rats were evenly randomized into 6
      groups of 8. MDA (P = 0.001), MPO (P = 0.001), NF-kappaB (P = 0.003), caspase-3
      expression (P = 0.002), and liver injury scores (P = 0.002) increased
      significantly in the OJ group compared with the sham group. Compared with the OJ
      group, MDA (P = 0.030) and MPO levels (P = 0.001), and liver injury scores (P =
      0.033) were decreased significantly in the OJ + sulfasalazine group. In the OJ +
      sulfasalazine + LPS and OJ + LPS + sulfasalazine groups, MDA (P = 0.008 and P =
      0.023, respectively) and MPO (both, P = 0.001) were significantly decreased;
      however, liver NF-kappaB, caspase-3 expression, and liver injury scores were not
      significantly different compared with the OJ + LPS group. There was no
      significant difference between the OJ + LPS + sulfasalazine and OJ +
      sulfasalazine + LPS groups in regard to all end points when comparing the effects
      of sulfasalazine administered before or after sepsis. CONCLUSIONS: Sulfasalazine
      was associated with decreased neutrophil accumulation and lipid peroxidation in
      these rats with OJ. Administration of sulfasalazine before or after LPS-induced
      sepsis was associated with a reduction in lipid peroxidation and neutrophil
      accumulation; however, it did not attenuate histologic liver damage. There was no
      difference between the findings when sulfasalazine was administered before or
      after sepsis in OJ.

PMID- 24683242
TI  - Effects of travoprost in the treatment of open-angle glaucoma or ocular
      hypertension: A systematic review and meta-analysis.
AB  - BACKGROUND: A 2005 meta-analysis suggests that lowering intraocular pressure
      (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG) is
      beneficial in reducing the risk for visual field loss in the long term.
      OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and toler
      ability of travoprost and latanoprost in patients with OAG or OHT. METHODS:
      Pertinent studies published from 1996 to 2008 were identified using systematic
      searches of major literature databases, including the Cochrane Library, MEDLINE,
      EMBASE, and the Chinese Biomedicine Database. Internet searches of major search
      engines, professional associations' Web sites, and manufacturers' databases were
      also performed. Randomized controlled trials (RCTs) comparing the effects of
      travoprost 0.004% and latanoprost 0.005% in patients with OAG or OHT were
      selected. The primary efficacy measure was the weighted mean difference (WMD) in
      the IOP reduction (IOPR). The primary tolerability measure was the relative risk
      (RR) for adverse events. The pooled effects were calculated using the random
      effects model. RESULTS: Seventeen studies (1491 patients) were included in the
      meta-analysis, 4 of which were of poor quality based on Jadad scoring. Travoprost
      was associated with significantly greater diurnal mean IOPRs compared with
      latanoprost at 2 weeks and 2 months (WMDs [95% CI] mm Hg: 2 weeks, 1.47 [0.33 to
      2.62]; 2 months, 0.71 [0.04 to 1.38]); these values were not significant at 1
      (0.81 [-0.78 to 2.40]), 3 (0.01 [-0.50 to 0.52]), and 6 months (0.27 [-0.40 to
      0.95]). When the 4 studies of low quality were excluded, no significant treatment
      differences in diurnal IOPR were found. IOPR measured at 5 pm was significantly
      greater with travoprost compared with latanoprost at 2 weeks (WMD [95% CI], 0.87
      mm Hg [0.40 to 1.33]); these values were not significant at 1 (WMD [95% CI], 0.60
      mm Hg [0.00 to 1.20], 2 (0.65 [-0.69 to 1.99]), 3 (0.04 [-0.51 to 0.59]), 6 (0.00
      [-0.68 to 0.68]), and 12 months (0.30 [-0.36 to 0.96]). Travoprost was associated
      with a significantly greater frequency of hyperemia than was latanoprost (RR =
      1.72 [95% CI, 1.33 to 2.23]). Rates of serious ocular adverse events did not
      differ significantly between travoprost and latanoprost (cystoid macular edema:
      RR = 0.22 [95% CI, 0.03 to 1.76]; cataract: RR = 2.29 [95% CI, 0.90 to 5.83]).
      CONCLUSIONS: The findings from the present meta-analysis of these 17 RCTs suggest
      that there were no significant differences between travoprost and latanoprost in
      IOPR in these patients with OHT or OAG. Both agents were generally well
      tolerated.

PMID- 24683241
TI  - Effectiveness and tolerability of NSAIDs in the prophylaxis of pancreatitis after
      endoscopic retrograde cholangiopancreatography: A systematic review and meta
      analysis.
AB  - BACKGROUND: Acute pancreatitis is a common complication of endoscopic retrograde
      cholangiopancreatography (ERCP). The beneficial effects of pharmaco-logic
      treatment of acute pancreatitis are unclear. Although the prophylactic use of
      NSAIDs for the reduction of the risk for pancreatic injury after ERCP has been
      assessed, the beneficial effects of NSAIDs on pancreatic injury are still being
      debated. OBJECTIVE: The aim of this study was to determine the effectiveness and
      tolerability of NSAIDs in the prophylaxis of post-ERCP pancreatitis (PEP).
      METHODS: MEDLINE (January 1966-January 2009), EMBASE (January 1966-January 2009),
      and the Cochrane Central Register of Controlled Trials (Issue 1, 2009) were
      searched using the key terms: pancreatitis, post-ERCP pancreatitis, nonsteroidal
      anti-inflammatory drugs, indomethacin, and diclofenac. The methods recommended by
      the Cochrane Collaboration and the Quality of Reporting Meta-Analyses guideline
      were used to conduct a systematic review and meta-analysis of randomized
      controlled trials (RCTs) of NSAIDs in the prevention of PEP. RESULTS: Four
      multinational RCTs were included in the meta-analysis (969 patients). The pooled
      odds ratio for NSAIDs for mild PEP was 0.69 (95% CI, 0.40-1.17; P = NS); moderate
      to severe PEP, 0.22 (95% CI, 0.05-1.01; P = 0.05); PEP (pooled), 0.44 (95% CI,
      0.21-0.93; P = 0.03); in high-risk patients, 0.49 (95% CI, 0.17-1.39; P = NS);
      and in low-risk patients, 0.29 (95% CI, 0.12-0.71; P = 0.006). No evidence of
      publication bias was found. CONCLUSION: Based on the findings from the present
      systematic review of 4 RCTs, NSAIDs were effective and well tolerated in the
      prevention of PEP, especially in low-risk patients.

PMID- 24683243
TI  - Comparison of effect of premixed lidocaine in propofol with or without ketorolac
      pretreatment with placebo on reducing pain on injection of propofol: A
      prospective, randomized, double-blind, placebo-controlled study in adult Korean
      surgical patients.
AB  - BACKGROUND: Pain on injection of propofol is a common adverse event. OBJECTIVE:
      The aim of this study was to investigate the effect of a combination of ketorolac
      pretreatment and premixed lidocaine in propofol compared with placebo on propofol
      injection pain. METHODS: In this prospective, randomized, double-blind, placebo
      controlled study, Korean patients scheduled for elective plastic surgery were
      randomized to 1 of 3 groups. Group A received 15 mg ketorolac in saline IV as
      pretreatment. Groups B and C received 3 mL saline IV as pretreatment. Sixty
      seconds after pretreatment, groups A and B received a mixture of lidocaine 1% in
      propofol 1% at a 1:10 ratio and group C received propofol 1% alone. Pain during
      propofol injection was assessed on a 4-point scale (0 = none, 1 = mild, 2 =
      moderate, 3 = severe). RESULTS: Ninety patients (41 men, 49 vvomen; mean age,
      41.7 years; mean weight, 63 kg) completed the study. The overall incidence of
      pain on propofol injection was significantly lower in groups A (16.7%) and B
      (36.7%) than in group C (83.3%; both, P < 0.001). There was no significant
      difference in the incidence of pain between groups A and B. However, the patients
      in group A reported a significantly lower incidence of moderate (0% vs 33.3%; P <
      0.001) and severe pain (0% vs 20%; P = 0.024) compared with those in group C.
      There were no significant differences in the incidences of moderate and severe
      pain between the B and C groups. CONCLUSIONS: In this Korean population, premixed
      lidocaine in propofol with or without ketorolac pretreatment was associated with
      significantly less pain when compared with placebo. The combination of ketorolac
      pretreatment and premixed lidocaine in propofol was more effective in decreasing
      the incidence of moderate or severe pain compared with placebo.

PMID- 24683244
TI  - Effect of memantine on plasma concentrations of carbamazepine and phenytoin in
      rats: A controlled experimental study.
AB  - BACKGROUND: Elderly patients, especially those with Alzheimer's disease, may be
      prescribed memantine and an antiepileptic drug concurrently. OBJECTIVE: The aim
      of this study was to compare the interaction of memantine with phenobarbital (an
      enzyme inducer) and chloramphenicol (an enzyme inhibitor) on plasma
      concentrations of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZE), and phenytoin in
      an experimental model. METHODS: Eight groups of rats (200-230 g) were treated for
      14 days each. In groups 1 and 2, phenobarbital 50 mg/kg was administered daily as
      an enzyme inducer 60 minutes before CBZ 50 mg/kg or phenytoin 30 mg/kg
      administration, respectively. In groups 3 and 4, chloramphenicol 300 mg/kg was
      administered daily as an enzyme inhibitor 60 minutes before CBZ or phenytoin
      administration, respectively. In groups 5 and 6, memantine 20 mg/kg was
      administered daily 60 minutes before CBZ or phenytoin, respectively. In group 7,
      CBZ alone was administered daily; in group 8, phenytoin alone was administered
      daily. Two hours after the last intragastric gavage, animals were anesthetized
      with ether and 2 mL of blood was drawn from the heart into a syringe containing
      EDTA. A validated method developed in this study was used for simultaneous
      determination of CBZ, CBZE, and phenytoin concentrations in rat plasma. RESULTS:
      The study comprised 8 groups of 9 male adult Wistar rats each. Compared with
      groups 7 and 8, concurrent use of CBZ or phenytoin with phenobarbital (groups 1
      and 2) was associated with significantly lower mean (SEM) plasma concentrations
      of CBZ (3.45 [0.16] vs 2.20 [0.21] MUg/mL; P < 0.001) and phenytoin (3.68 [0.09]
      vs 1.63 [0.15] MUg/mL; P < 0.001) and a significantly higher plasma CBZE
      concentration (9.85 [0.29] vs 11.18 [0.29] MUg/mL; P < 0.05). Concurrent use of
      CBZ or phenytoin with chloramphenicol (groups 3 and 4) was associated with
      significantly higher plasma concentrations of CBZ (4.81 [0.17] MUg/mL; P < 0.001)
      and phenytoin (6.24 [0.22] MUg/mL; P < 0.001) and a significantly lower plasma
      CBZE concentration (3.88 [0.25] MUg/mL; P < 0.001). Concurrent use of CBZ or
      phenytoin with memantine (groups 5 and 6) was not associated with a significant
      change in the plasma concentration of CBZ, CBZE, or phenytoin. CONCLUSION:
      Memantine was not associated with a significant change in the plasma
      concentration of CBZ, CBZE, or phenytoin in this experimental model.

PMID- 24683245
TI  - Effects of atorvastatin on smoking-induced alveolar injury in rat lungs.
AB  - BACKGROUND: Smoking is one of the most serious health care issues worldwide, as
      one third to one half of all people who smoke eventually use tobacco habitually.
      Chronic smoke exposure causes airway and lung parenchymal inflammation and the
      destruction of alveolar cell walls. Statins may have anti-inflammatory effects
      that would play a role in preventing the cellular damage associated with smoking.
      OBJECTIVE: The aim of this study was to investigate whether atorvastatin protects
      against smoking-induced inflammation in alveolar epithelial type I (ATI) and type
      II (ATII) cells in the lungs of rats. METHODS: Adult male albino Wistar rats (200
      250 g) were randomly divided into 3 groups and exposed to cigarette smoke 8 hours
      per day for 15 days. During that 15-day period, the 2 treatment groups received
      atorvastatin 0.5 or 1.0 mg/kg/d in 2 mL of methyl cellulose solution and the
      control group received 2 mL of methyl cellulose solution alone, all via
      nasogastric catheter. After the 15 days, the lungs were excised and the tissues
      were examined by transmission electron microscopy. RESULTS: Thirty rats were
      divided into 3 groups of 10 rats each. All rats survived the 15 days. In the
      atorvastatin 0.5-mg group, no changes were found in the ATI cells or in the blood
      air barrier. In the atorvastatin 1.0-mg group, we observed hyperplasia in the
      common basal membranes. Hypertrophy, mitochondrial crystolysis (MC), and
      intracytoplasmic edema (ICE) were detected in the ATI cells in the 1.0-mg group,
      while chromatin condensation, atrophic appearance, cell shrinkage, and cyto
      plasmic vacuolization were observed in the ATII cells. The rough endoplasmic
      reticulum (rER) tubules of the ATII cells appeared spiral-shaped. In the control
      group, minimal ICE was detected in the ATI cells. However, microvillus
      deformation, pseu-dopod formation, edema, mitochondrial swelling, and MC were
      observed in the ATII cells. We also observed MC, several pinocytic vesicles, and
      normal rER tubules in the endothelial cells of the control group. CONCLUSIONS:
      The administration of atorvastatin 0.5 mg/kg/d was associated with some
      attenuation of lung injury caused by smoke inhalation in these rat lungs.
      However, atorvastatin 1.0 mg/kg/d was associated with lung damage. Future studies
      are needed to evaluate the dose-response relationship of atorvastatin to smoking
      induced alveolar damage.

PMID- 24683246
TI  - Effectiveness and tolerability of rosiglitazone on insulin resistance and body
      composition in nondiabetic Thai patients undergoing continuous ambulatory
      peritoneal dialysis: A 12-week pilot study.
AB  - BACKGROUND: Patients with chronic renal insufficiency, especially those
      undergoing continuous ambulatory peritoneal dialysis (CAPD), normally have
      insulin resistance due to deficiencies in insulin secretion and degradation, as
      well as tissue resistance to insulin at both receptor and postreceptor levels.
      OBJECTIVE: The aim of this study was to investigate the effectiveness and
      tolerability of rosiglitazone on insulin resistance and body composition in
      patients without diabetes mellitus (DM) undergoing CAPD. METHODS: This pilot
      study included a pretest and posttest with a repeated-measure design in a small
      number of patients. CAPD patients without DM received rosiglitazone 2-mg tablets
      BID for 12 weeks. Homeostasis Model Assessment Index of Insulin Resistance (HOMA
      IR) and bioelectrical impedance analysis (BIA) were used to assess insulin
      resistance and body composition, respectively. Tolerability was assessed using
      laboratory analyses as well as physical examination findings to evaluate
      peripheral edema. Peripheral edema was assessed by the study investigators.
      RESULTS: Thirteen Thai patients (mean [SD] age, 54.17 [11.42] years [range, 35-85
      years]; body mass index [BMI], >20 to <30 kg/m(2); fasting blood glucose [FBG]
      concentration, <5.39 mmol/L) were included in the study. One patient was
      withdrawn due to illness unrelated to the study. No significant difference was
      found in FBG concentration between baseline and posttreatment (after 12 weeks of
      treatment) (5.45 [0.59] vs 5.24 [0.51] mmol/L), but fasting plasma insulin
      concentrations (28.50 [23.70] vs 10.15 [4.22] MUIU/mL; P = 0.005) and HOMA-IR
      score (6.70 [5.23] vs 2.40 [1.15]; P = 0.011) were significantly lower. There
      were no significant changes in weight or BMI from baseline to posttreatment.
      Seven subjects (58.3%) experienced weight gain at week 4, while 2 patients
      (16.7%) still had weight gain after 12 weeks of treatment. A significant increase
      was found between baseline and posttreatment in total body water (38.03 [4.55] vs
      42.44 [5.99] L; P = 0.018), extracellular fluid (20.24 [3.75] vs 26.22 [8.69] L;
      P = 0.005), plasma fluid (4.29 [0.80] vs 5.20 [0.93] L; P = 0.005), and
      interstitial fluid (14.99 [2.78] vs 17.68 [3.07] L; P = 0.040). Using BIA, no
      significant changes were observed in intracellular fluid, fat mass, or liver
      function. After 12 weeks of rosiglitazone administration, 2 patients (16.7%) had
      mild edema. CONCLUSIONS: Rosiglitazone 2 mg BID for 12 weeks was associated with
      significantly improved insulin resistance in this small group of nondiabetic Thai
      patients undergoing CAPD. There was a significant increase in total body water
      and extracellular fluid after administration of rosiglitazone for 12 weeks. There
      were no significant changes in FBG, weight, or BMI.

PMID- 24683247
TI  - Pharmacokinetics and tolerability of multiple-dose rosuvastatin: An open-label,
      randomized-sequence, three-way crossover trial in healthy Chinese volunteers.
AB  - BACKGROUND: Rosuvastatin has been reported to be beneficial in the treatment of
      dyslipidemia. The Cmax and AUC0-t of rosuvastatin were reported to be ~2 to 4
      times higher in Chinese subjects compared with white subjects after
      administration of a single 1-mg/kg dose. OBJECTIVES: The aims of this study were
      to assess the pharmacokinetics and tolerability of multiple doses of rosuvastatin
      in healthy Chinese volunteers. METHODS: This open-label, randomized-sequence, 3
      way crossover trial consisted of three 7-day treatment periods and two 10-day
      washout periods. Healthy volunteers were randomly allocated to 1 of 3 daily
      treatment regimens: rosuvastatin 5, 10, or 20 mg. To assess the pharmacokinetics
      and tolerability of rosuvastatin, blood samples were drawn before dosing (hour 0)
      on days 5, 6, and 7 and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, 72,
      and 96 hours after the final dose was administered on day 7. A validated HPLC
      MS/MS method was used to determine rosuvastatin levels. A 2-compartment
      pharmacokinetic model was fitted to the plasma concentration-time profiles
      obtained for each volunteer. Adverse events (AEs) were monitored throughout the
      study via subject interview, vital signs, and blood sampling. Serious AEs were
      those requiring hospitalization, treatment discontinuation, or resulting in
      death. RESULTS: Twelve healthy Chinese volunteers (6 men: mean [SD] age, 21.8
      [1.7] years; weight, 62.3 [5.8] kg; height, 174.3 [7.2] cm; 6 women: age, 20.8
      [1.2] years; weight, 53.2 [4.7] kg; height, 161.3 [4.3] cm) participated in and
      completed the trial. The mean (SD) steady-state Cmax was significantly greater
      after ro-suvastatin administration in the 20-mg group compared with the 5-mg
      group (37.69 [29.83] vs 6.17 [6.03] ng/mL; P = 0.04). The t1/2 was significantly
      greater in the 20-mg group (15.51 [6.43] hours) compared with the 5-mg group
      (5.65 [5.08] hours; P = 0.001) and the 10-mg group (8.58 [5.17] hours; P =
      0.002). The mean AUC0-t was significantly greater in the 20-mg group compared
      with the 5-mg group (349.16 [257.20] vs 40.63 [39.31] ng/mL/h; P = 0.02). All AEs
      were considered by the investigators to be mild in intensity, with the exception
      of 2 cases of abdominal discomfort (1 man and 1 woman, both in the 5-mg dose
      group). Two women in the 20-mg group experienced dizziness and cold sweats
      simultaneously. In the 10-mg group, 1 woman had abdominal discomfort and nausea
      and 1 woman had jaw pain. All reported AEs were considered possibly related to
      study drug administration. CONCLUSIONS: In this small study in healthy Chinese
      volunteers, rosuvastatin systemic exposure appeared to be dose-proportional over
      the dosing range of 5 to 20 mg with multiple-dose administration. There was no
      accumulation of rosuvastatin in the body with the 5- and 10-mg doses. However,
      the results suggest that rosuva-statin might accumulate when the dose is
      increased to 20 mg. No serious AEs occurred in any of the 3 dosing groups.

PMID- 24683248
TI  - Tolerability and effectiveness of (S)-amlodipine compared with racemic amlodipine
      in hypertension: a systematic review and meta-analysis.
AB  - BACKGROUND: Amlodipine is a calcium channel blocker prescribed for the management
      of angina and hypertension. As a racemic mixture, amlodipine contains (R)- and
      (S)-amlodipine isomers, but only (S)-amlodipine as the active moiety possesses
      therapeutic activity. Based on pharmacologic research, it remains uncertain if
      (S)-amlodipine alone has similar efficacy and fewer associated adverse events
      (AEs) compared with the racemic mixtures. OBJECTIVE: The aim of this systematic
      review and meta-analysis was to determine the effectiveness and tolerability of
      (S)-amlodipine compared with that of racemic amlodipine. METHODS: A systematic
      literature search was performed using MEDLINE (1966-2009), EMBASE (1966-2009),
      the Cochrane Central Register of Controlled Trials (issue 3, 2009), the Chinese
      Biomedical Database (1978-2009), and the China National Knowledge Internet (1980
      2009). All randomized controlled trials (RCTs) comparing (S)-amlodipine 2.5 mg
      and racemic amlodipine 5.0 mg in the treatment of hypertension were included in
      the review. The outcome measures to be collected were cardiovascular events,
      systolic blood pressure (SBP), diastolic BP (DBP), and AEs. Quality assessments
      of clinical trials were conducted using a modified Jadad Scale, with trials being
      rated as low quality (score 0-3) or high quality (score 4-7). Meta-analysis of
      the included studies was performed using RevMan software. RESULTS: Of the 229
      references identified, 214 were excluded after screening the titles, abstracts,
      or full texts. Fifteen RCTs were included, of which 13 were in Chinese and 2 in
      English. Based on the Jadad Scale score, 3 of the RCTs were classified as high
      quality (score 5 or 6) and the remaining 12 as low quality (score 1-3). None of
      the trials evaluated cardiovascular events beyond 40 weeks. Meta-analysis of the
      15 trials indicated that (S)-amlodipine was not significantly different from
      racemic amlodipine in the effect on BP. When only high-quality studies were
      included, after 4 weeks' treatment, the weighted mean difference (WMD) of SBP and
      DBP decrease (1 study) was -2.84 (95% CI, -6.42 to 0.74) with (S)-amlodipine and 
      1.71 (95% CI, -3.48 to 0.06) with racemic amlodipine. After 8 weeks' treatment,
      the WMD of SBP and DBP decrease (2 studies) was -1.13 (95% CI, -5.29 to 3.03) and
      -1.34 (95% CI, -2.67 to -0.01), respectively. The risk difference (RD) for the
      number of patients who experienced AEs with (S)-amlodipine and racemic amlodipine
      was found to be -0.04 (95% CI, -0.06 to -0.02). When all the trials were
      included, (S)-amlodipine treatment was associated with significantly less edema
      than racemic amlodipine (RD, -0.02; 95% CI, -0.03 to 0.00); however, when only
      high-quality studies (2 studies) were included, no difference was found between
      the 2 groups (RD, 0.01; 95% CI, -0.02 to 0.03). One high-quality study found
      significant differences in increases in aspartate and alanine aminotransferase
      activities in the 2 groups (RD, 0.08; 95% CI, 0.01 to 0.05). No significant
      differences between the 2 groups were found in the incidence of headache (RD,
      0.00; 95% CI, -0.02 to 0.01) or flushing (RD, -0.01; 95% CI, -0.02 to 0.00).
      CONCLUSIONS: The majority of the clinical trials comparing (S)-amlodipine and
      racemic amlodipine treatment were low quality (12/15 [80%]). According to the
      limited evidence, there were no significant differences between (S)-amlodipine
      2.5 mg and racemic amlodipine 5.0 mg in controlling BP. When all the trials were
      considered, (S)-amlodipine treatment was associated with significantly less edema
      than racemic amlodipine; however, when only high-quality trials were included, no
      significant difference was found. More long-term, high-quality RCTs with
      cardiovascular events as the primary outcome are needed to compare the safety and
      efficacy of (S)-amlodipine and racemic amlodipine.

PMID- 24683249
TI  - The reporting quality, scientific rigor, and ethics of randomized placebo
      controlled trials of traditional Chinese medicine compound formulations and the
      differences between Chinese and non-Chinese trials.
AB  - BACKGROUND: An increasing number of randomized placebo-controlled trials
      involving traditional Chinese medicine (TCM) compound formulations have been
      implemented worldwide. OBJECTIVE: The aim of this study was to assess the
      reporting quality, scientific rigor, and ethics of randomized placebo-controlled
      trials of TCM compound formulations and compare these differences between Chinese
      and non-Chinese trials. METHODS: English-language databases included the
      following: PubMed, OVID, EMBASE, and Science Citation Index Expanded. Chinese
      language databases included the following: Chinese Biomedical Literature
      Database, Wanfang Database, Chinese Scientific and Technological Periodical
      Database, and the China National Knowledge Infrastructure. All were searched from
      respective inception to March 2009 to identify randomized placebo-controlled
      trials involving TCM compound prescriptions. Two reviewers independently assessed
      the retrieved trials via a modified Consolidated Standard of Reporting Trials
      (CONSORT) checklist and some evaluation indices that embodied the TCM
      characteristics or the scientific rigor and ethics of placebo-controlled trials.
      Trial publishing time was divided into 3 intervals: phase 1 (<=1999); phase 2
      (2000-2004); and phase 3 (2005-2009). The number and percentage of trials
      reporting each item and the corresponding differences between Chinese (mainland
      China, Hong Kong, and Taiwan) and non-Chinese (eg, Japan, United States,
      Australia, Korea, and United Kingdom) trials were calculated. Moreover, the
      influence of trial publishing time on the reporting of CONSORT items and the
      differences in the number of items reported for each time interval between
      Chinese and non-Chinese trials were assessed. RESULTS: A total of 324 trials from
      China and 51 trials from other countries were included. A mean of 39.7% of the
      CONSORT items across all Chinese trials and 50.2% of the items across all non
      Chinese trials were reported. The number of the reported CONSORT items all
      increased over time in both groups and the gap between Chinese articles and non
      Chinese articles gradually decreased. Additionally, of the 324 Chinese articles,
      137 (42.28%) reported TCM syndrome type, 113 (34.88%) reported the diagnostic
      criteria of diseases for TCM, and 69 (21.30%) reported efficacy evaluation
      indices of TCM. Of the non-Chinese articles, 3 (5.88%) reported TCM syndrome type
      and 1 (1.96%) reported the diagnostic criteria of diseases and evaluation indices
      of efficacy for TCM. It was found that 45.37% and 6.17% of Chinese articles
      reported the standard intervention for the diseases being treated and the
      emergency plan, respectively, compared with 23.53% and 9.80% for the non-Chinese
      articles; 33.02% and 10.49% of Chinese articles reported informed consent and
      ethics committee approval, respectively, compared with 92.16% and 82.35% for the
      non-Chinese articles. With regard to placebo ethics, 38.89% of the Chinese trials
      and 23.53% of the non-Chinese trials found it would not be ethically acceptable
      to use placebo alone in the control group. CONCLUSIONS: The data indicate that
      the reporting quality of the included trials on TCM compounds has improved over
      time, but still remains poor regardless of Chinese or non-Chinese trials. Across
      all trials, particularly Chinese trials, the reporting of the CONSORT items was
      inadequate (39.7%). The difference in the mean number of the reported CONSORT
      items between Chinese trials and non-Chinese trials narrowed from phase 1 (10.0
      vs 13.8) to phase 3 (14.4 vs 17.4). Moreover, a large number of trials,
      especially non-Chinese trials (94.1%), were lacking syndrome differentiation of
      TCM. More importantly, in many placebo-controlled trials, especially Chinese
      trials, the use of placebo was not justified and was ethically contradictory.

PMID- 24683250
TI  - Bioavailability of oral carisoprodol 250 and 350 mg and metabolism to
      meprobamate: A single-dose crossover study.
AB  - BACKGROUND: Carisoprodol is a skeletal muscle relaxant indicated for use in the
      treatment of acute, painful musculoskeletal conditions. Two randomized,
      controlled clinical trials have reported that carisoprodol 250 mg QID was equally
      effective as and better tolerated than carisoprodol 350 mg QID. OBJECTIVES: The
      primary objective of the current study was to determine the relative
      bioavailability of carisoprodol and its metabolite, meprobamate, with singledose
      administration of 250- and 350-mg tablets. A secondary objective of the study was
      to determine whether lowering the carisoprodol dose would decrease plasma
      meprobamate concentrations. METHODS: This single-dose, randomized, open-label,
      crossover study enrolled healthy volunteers. Each dose was administered with
      water in the morning; after a 7-day washout, subjects received the alternate
      dose. Blood samples were drawn at prespecified times over a 48-hour period. For
      tolerability assessment, subjects underwent a physical examination, including 12
      lead ECG. RESULTS: A total of 24 subjects were enrolled (12 men, 12 women; mean
      age, 22.8 years). The dose-adjusted AUC0-infinity values for carisoprodol were
      5.29 MUg/mL/h with the 250-mg tablet and 5.75 MUg/mL/h with the 350-mg tablet
      (relative bioavailability, 92%). The mean (SD) Cmax values of carisoprodol and
      meprobamate after administration of the 250-mg carisoprodol tablet were 1.24
      (0.49) and 1.84 (0.31) MUg/mL, respectively, compared with 1.78 (0.97) and 2.46
      (0.47) MUg/mL with the 350-mg tablet. AUC0-infinity was dose proportional, and
      the apparent t1/2 values at the terminal phase were 1.74 hours with the 250-mg
      tablet and 1.96 hours with the 350-mg tablet. There were 3 mild adverse events
      considered possibly treatment related (weakness, dizziness, and drowsiness);
      these were reported in 2 subjects with 350-mg carisoprodol. CONCLUSIONS: In this
      small study in healthy fasting subjects, the exposure to carisoprodol and
      meprobamate was dose proportional between the single 250- and 350-mg doses. Both
      doses were generally well tolerated.

PMID- 24683251
TI  - In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent
      pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
AB  - BACKGROUND: It was hypothesized that the observed slight immunostimulatory effect
      of the 23-valent pneumococcal polysaccharide (pneumo-23) vaccine might be due to
      the presence of low levels of zwitterionic motifs. Therefore, it was hypothesized
      further that introducing zwitterionic motifs experimentally into polysaccharides
      of pneumo-23 vaccine might render it an effective immunostimulatory agent.
      OBJECTIVE: This study was conducted to assess the in vitro immunostimulatory
      effect of zwitterionized pneumo-23 (Z-P23) vaccine compared with the
      nonzwitterionized commercial pneumo-23 (C-P23) vaccine. METHODS: In vitro
      proliferation, ELISA-based in vitro cytokine synthesis (interleukin [IL]-2,
      interferon [IFN]-gamma, and IL-10), and immunofluorescence microscopy-based
      immune cell profiling (CD4(+), CD8(+), and CD21(+) cells) assays were used to
      evaluate the immunostimulatory effect of Z-P23 on peripheral blood mononuclear
      cells (PBMC) of immunosuppressed cancer (IC) patients and healthy control
      subjects in comparison with PBMC exposed to C-P23, concanavalin A (positive
      control), and phosphate-buffered saline (PBS) (negative control). RESULTS: Z-P23
      induced proliferation of PBMC in the IC (81.1%) and control (75.1%) groups
      significantly higher than that achieved with concanavalin A in the IC group
      (51.0%; P = 0.01) but not in the control group (89.2%; P = NS). This was also
      significantly higher than that achieved with C-P23 in the IC (4.8%; P < 0.001)
      and control (6.2%; P < 0.001) groups. Z-P23 induced IL-2 and IFN-gamma synthesis
      in the IC group (0.61 and 0.45 ng/mL, respectively) significantly more than that
      with C-P23 (0.4 and 0.45 ng/mL; P = 0.002 and P <0.001), concanavalin A (0.45 and
      0.31 ng/mL; P = 0.021 and P = 0.03), and PBS (0.41 and 0.29 ng/mL; P = 0.005 and
      P = 0.04) but not the control group. Z-P23 induced expansion of CD4(+), CD8(+),
      and CD21(+) lymphocytes (39.3%, 42.7%, and 8.1%, respectively) in the IC group
      higher than that with C-P23 (28.3%, 30.1%, and 5.5%; P = 0.01, P = 0.003, and P =
      NS), concanavalin A (27.2%, 35.8%, and 4.1%; P = 0.02, P = 0.048, and P = 0.035),
      and PBS (25.6%, 31.9%, and 4.2%; P = 0.018, P = 0.02, and P = 0.045). CONCLUSION:
      The in vitro immunostimulatory potential of Z-P23 was clearly observed on PBMC of
      IC patients as well as, to a lesser extent, healthy control subjects, stimulating
      the synthesis of core cytokines of T-helper 1, and primarily inducing CD4(+) and
      CD8(+)T cells.

PMID- 24683252
TI  - Comparison of ramosetron, dexamethasone, and a combination of ramosetron and
      dexamethasone for the prevention of postoperative nausea and vomiting in Korean
      women undergoing thyroidectomy: A double-blind, randomized, controlled study.
AB  - BACKGROUND: Thyroidectomy is associated with a relatively high incidence of
      postoperative nausea and vomiting (PONV), ranging from 51% to 76%. Because these
      symptoms are distressing for patients, prophylactic medication to avoid or reduce
      PONV is recommended. OBJECTIVE: The aim of the present study was to compare the
      efficacy of ramosetron, dexamethasone, and a combination of ramosetron and
      dexamethasone in preventing PONV in Korean women undergoing thyroidectomy.
      METHODS: In this double-blind, randomized, controlled trial, consecutive adult
      female patients who were scheduled to undergo thyroidectomy under general
      anesthesia at the Kyungpook National University Hospital (Daegu, Korea) were
      randomly assigned to receive ramosetron 0.3 mg alone, dexamethasone 8 mg alone,
      or a combination of ramosetron 0.3 mg and dexamethasone 8 mg administered
      intravenously as a single dose immediately after induction of anesthesia. The
      primary end point of this study was the total PONV rate up to 24 hours
      postanesthesia. The secondary end points were the incidence of nausea, incidence
      of vomiting, severity of nausea (0 = no nausea to 10 = nausea as bad as it could
      be), use of rescue antiemetic drugs, and the occurrence of adverse events (AEs)
      determined through interview or spontaneous patient report for 24 hours
      postanesthesia. RESULTS: A total of 198 female patients were approached for study
      inclusion, 18 of whom were excluded. Therefore, 180 Korean women (mean [SD] age,
      46.5 [12.6] years; height, 159.8 [2.7] cm; weight, 53.2 [3.6] kg) were enrolled
      and completed the study. The total PONV rates up to 24 hours postanesthesia were
      35%, 13%, and 10% in the dexamethasone, ramosetron, and combination groups,
      respectively. The PONV rate was significantly lower in the combination group than
      in the dexamethasone alone group (P = 0.006). The PONV rate was not significantly
      different in the combination group compared with the ramosetron alone group. The
      PONV rate in the dexamethasone alone group was significantly higher than that in
      the ramosetron alone group (P = 0.03). The severity of nausea (median [25th-75th
      percentiles], 0 [0-0] vs 0 [0-4]; P = 0.009) and rate of use of rescue antiemetic
      drugs (5% vs 27%; P = 0.006) were significantly lower in the combination group
      than in the dexamethasone alone group, whereas the severity of nausea (median
      [25th-75th percentiles], 0 [0-0] vs 0 [0-0]) and rate of use of rescue antiemetic
      drugs (5% vs 7%) were not significantly different between the combination and
      ramosetron alone groups. The severity of nausea (median [25th-75th percentiles],
      0 [0-4] vs 0 [0-0]; P = 0.033) and the rate of use of rescue antiemetic drugs
      (27% vs 7%; P = 0.018) were significantly higher in the dexamethasone alone group
      than in the ramosetron alone group. The rates of AEs (headache: 15%, 20%, and
      18%; dizziness: 18%, 22%, and 15%) were not significantly different in the
      dexamethasone alone, ramosetron alone, or combination groups, respectively.
      CONCLUSIONS: The combination of ramosetron and dexamethasone was more effective
      in reducing PONV than was dexamethasone monotherapy. However, the combination did
      not show additional benefits compared with ramosetron alone in preventing PONV
      after thyroidectomy in these Korean women.

PMID- 24683254
TI  - The Charles R. Ream, MD, Award for excellence-2009.

PMID- 24683255
TI  - Analgesic effects of ketamine infusion therapy in korean patients with
      neuropathic pain: A 2-week, open-label, uncontrolled study.
AB  - BACKGROUND: The overexcitation of the N-methyl-D-aspartate receptor complex
      appears to play a critical role in the development of neuropathic pain, and
      ketamine acts as an antagonist to that receptor. Some publications have reported
      on the prominent relief of neuropathic pain with intravenous or subcutaneous
      ketamine infusions or a single-dose intravenous ketamine injection despite
      adverse effects. OBJECTIVES: The primary objective of this study was to determine
      the analgesic effect of intravenous ketamine infusion therapy for neuropathic
      pain refractory to conventional treatments. Secondary objectives included
      identifying the variables related to the analgesic effect and the pain
      descriptors susceptible to ketamine infusion. METHODS: This 2-week, open-label,
      uncontrolled study was conducted in Korean patients with neuropathic pain
      recruited from the Samsung Seoul Hospital (Seoul, Republic of Korea) outpatient
      pain management unit. Patients were required to have a pain severity score >5
      (visual analog scale [VAS], where 0 = no pain and 10 = worst pain imaginable)
      over a period of >=1 month while on standard treatment. The patients were
      required to have shown no benefit from standard treatment and no pain relief
      lasting over 1 month. The ketamine infusion therapy was composed of 3 sessions
      performed consecutively every other day. Midazolam was administered concomitantly
      to reduce the occurrence of central nervous system-related adverse events (AEs)
      secondary to ketamine. Each session was as follows: ketamine 0.2 mg/kg and
      midazolam 0.1 mg/kg were administered intravenously for 5 minutes as a loading
      dose, followed by a continuous infusion of ketamine 0.5 mg/kg/h and midazolam
      0.025 mg/kg/h for 2 hours. AEs were assessed in the following ways: close
      monitoring of ECG, blood pressure, oxygen saturation, and evaluating the need for
      treatment of AEs during infu- sion and until discharge by an attending
      anesthesiologist; an open question about discomfort at the end of each session;
      spontaneous reports about AEs during each session; and the patients' and
      caregivers' checklist of AEs occurring at home for 2 weeks after discharge. All
      the descriptors of pain expressed by the patients in Korean were recorded and
      translated into appropriate English terminology on the basis of the literature on
      Korean verbal descriptors of pain. Each of the translated pain descriptors was
      then classified into 1 of 18 sensory items. RESULTS: The overall VAS score for
      pain decreased from a baseline mean (SD) of 7.20 (1.77) to 5.46 (2.29) (P <
      0.001) 2 weeks after treatment in 103 patients (53 males and 50 females; mean
      age, 52.56 [17.33] years) who completed the study. Variables such as age, sex,
      and the duration and diagnosis of pain were not found to be associated with
      analgesic effect. Seven of the 18 pain descriptors were found to have a
      significant response to ketamine infusion treatment between baseline and 2 weeks
      follow-up: burning pain (P = 0.008); dull, aching pain (P < 0.001); overly
      sensitive to touch (P = 0.002); stabbing pain (P = 0.008); electric pain (P =
      0.031); tingling pain (P < 0.001); and squeezing pain (P < 0.001). A total of 52
      patients reported AEs: 33 during infusion and 44 during recovery and up to 2
      weeks follow up. The most commonly reported AEs were snoring (15 [15%]) during
      infusion and dizziness (43 [42%]) during recovery. CONCLUSIONS: Ketamine infusion
      therapy was associated with reduced severity of neuropathic pain and generally
      well tolerated for up to 2 weeks in these patients with neuropathic pain
      refractory to standard treatment. Variables such as sex, age, and the diagnosis
      and duration of pain had no association with the analgesic effect of this
      treatment. Randomized controlled trials are needed to evaluate the efficacy and
      tolerability of treatment with ketamine infusion.

PMID- 24683256
TI  - Effects of a topical hemostatic agent on an epistaxis model in rabbits.
AB  - BACKGROUND: Ankaferd BloodStopper (ABS) is a standardized herbal compound
      consisting of 5 different plant extracts. ABS, as a topical medicinal product,
      has been approved by the Turkish Ministry of Health for the management of dermal,
      external postsurgical and postdental surgery bleedings. OBJECTIVE: The aim of
      this study was to assess the hemostatic effect of ABS in an experimental
      epistaxis model. METHODS: Adult female New Zealand rabbits were used in this
      study. Standardized full-thickness mucosal wounds were created to provide
      bleeding on the right and left side of the nasal septum of rabbits with a 3-mm
      surgical punch. To stop bleeding, the wounds were treated with topical ABS on one
      side and with topical isotonic saline solution as a control on the other side of
      the nasal septum. Investigators were blinded to treatment. The duration of
      bleeding was measured in order to compare the hemo-static effect with ABS or
      topical isotonic saline solution. The wounds were observed for the duration of
      bleeding in order to compare the hemostatic effect of ABS with isotonic saline
      solution and acute adverse effects (AEs) for 30 minutes by a researcher blinded
      to treatment groups. RESULTS: Six rabbits (mean weight, 2.6 kg [range, 2.3-3.1
      kg]) were used in this study. Mean (SD) bleeding time in the wounds administered
      ABS (98 [17] sec) was significantly less than that of the controls (266 [36] sec;
      P = 0.004). No AEs were observed up to 30 minutes after study initiation.
      CONCLUSION: This study suggests that ABS may be more effective in reducing time
      to hemostasis when compared with isotonic saline solution in this epistaxis model
      in rabbits.

PMID- 24683257
TI  - Effects of naloxone and flumazenil on antinociceptive action of acetaminophen in
      rats.
AB  - BACKGROUND: Studies of acetaminophen suggest that multiple nociceptive pathways
      are involved in the drug's analgesic action. OBJECTIVE: The purpose of this study
      was to determine whether naloxone and flumazenil were able to modify or
      antagonize the antinociceptive effect of acetaminophen in rats. METHODS: Adult
      albino Wistar rats were used in the study and randomly allocated to 1 of 4
      groups. The acetaminophen group (A group) was administered IP saline and then 300
      mg/kg IP acetaminophen 5 minutes thereafter. The acetaminophen + naloxone group
      (AN group) was pretreated with 1 mg/kg IP naloxone, followed by 300 mg/kg IP
      acetaminophen 5 minutes later. The acetaminophen + flumazenil group (AF group)
      was pretreated with 1 mg/kg IP flumazenil, followed by 300 mg/kg IP acetaminophen
      5 minutes later. The control group received 2.5 mL IP saline, followed by an
      additional 2.5 mL IP injection of saline 5 minutes later. The paw-withdrawal
      latency period of the rats was assessed by an investigator blinded to treatment
      using the hot-plate test at 30, 45, 60, and 90 minutes after administration of
      acetaminophen. RESULTS: Thirty-two rats were evenly randomized by envelope method
      into 4 groups of 8 rats each. Baseline values for the A, AN, AF, and control
      groups were not significantly different (9.1 [2.3], 10.5 [2.7], 9.8 [3.0], and
      8.9 [1.4] sec, respectively). In the AF group, flumazenil appeared to antagonize
      the analgesic effect exerted by the acetaminophen in the hot-plate test (30 min,
      10.3 [3.7] sec; 45 min, 11.7 [5.1] sec; 60 min, 12.1 [5.1] sec; and 90 min, 12.2
      [4.9] sec) and values were not significantly different from those obtained in the
      control group (30 min, 9.8 [2.2] sec; 45 min, 9.0 [1.6] sec; 60 min, 9.2 [1.6]
      sec; and 90 min, 8.5 [2.0] sec). In the AN group, naloxone did not significantly
      affect the values observed in the hot-plate test (30 min, 18.0 [4.5] sec; 45 min,
      21.5 [7.8] sec; 60 min, 20.5 [5.9] sec; and 90 min, 22.3 [7.4] sec) and values at
      all time points were not significantly different from those obtained in the A
      group (30 min, 17.8 [7.6] sec; 45 min, 20.9 [6.9] sec; 60 min, 21.5 [7.3] sec;
      and 90 min, 23.8 [8.6] sec). All postbaseline values in the A and AN groups were
      significantly increased versus baseline and versus the control group values (all,
      P < 0.05). All postbaseline values in the A group were significantly greater than
      those in the AF group (all, P < 0.05). CONCLUSION: Flumazenil antagonized the
      analgesic effect exerted by acetaminophen, while naloxone had no significant
      effect on acetaminophen's antinociceptive action in this pain model in rats.

PMID- 24683258
TI  - Effects of intraperitoneal melatonin on caustic sclerosing cholangitis due to
      scolicidal solution in a rat model.
AB  - BACKGROUND: Hydatid disease is a worldwide health problem. Treatment is surgical
      or percutaneous, using scolicidal agents. Caustic sclerosing cholangitis might
      develop after the contact of scolicidal agents with the biliary ducts. Melatonin,
      an antioxidant, anti-inflammatory, and anticarcinogenic agent, might be used in
      the treatment of caustic sclerosing cholangitis due to its possible preventive
      effects on fibrosis and cell damage. OBJECTIVE: The aim of the study was to
      investigate the effects of melatonin on an experimentally developed caustic
      sclerosing cholangitis with scolicidal solution (formalin) in a rat model.
      METHODS: Forty female Sprague-Dawley rats aged 11 to 13 weeks and weighing 250 +/
      30 g were randomly assigned to 1 of 4 groups of 10: formalin 5% at 0.5 mL/d +
      melatonin placebo; formalin placebo + intraperitoneal melatonin 10 mg/kg/d;
      formalin 5% at 0.5 mL/d + melatonin 10 mg/kg/d; and formalin placebo and
      melatonin placebo (control). Hepatobiliary function was assessed using dynamic
      scintigraphy with technetium-99m-mebrofenin on study day 60. The histology of the
      liver and biliary duct specimens was examined on study day 60. In each group,
      histopathologic alterations were scored as absent, slight, mild, or severe.
      RESULTS: Mean severity scores for parenchymal necrosis in the liver (P < 0.01),
      portal fibrosis (P < 0.01), biliary duct proliferation (P < 0.001), cholangitis/
      pericholangitis (P < 0.01), hyperemia in the biliary ducts (P < 0.01), and
      fibrosis (P < 0.01) were significantly lower in rats treated with formalin +
      melatonin compared with those treated with formalin alone. No significant
      differences were observed between the 3 treatment groups with respect to t1/2, a
      parameter used to assess the secretion function of the hepatocytes. However, the
      t1/2 was significantly longer in the treatment groups compared with controls (P <
      0.001). CONCLUSION: In this experimental study in a rat model of caustic
      sclerosing cholangitis, the histopathologic and scintigraphic findings suggested
      that melatonin is effective in attenuating the damage caused by scolicidal agents
      on the liver and biliary ducts.

PMID- 24683259
TI  - Effect of a variety of Chinese herbs and an herb-containing dentifrice on
      volatile sulfur compounds associated with halitosis: An in vitro analysis.
AB  - BACKGROUND: The principal components of halitosis are volatile sulfur compounds
      (VSCs) such as hydrogen sulfide, methyl mercaptan, and dimethylsulfide or
      compounds such as butyric acid, propionic acid, putrescine, and cadaverine.
      OBJECTIVE: The aim of this study was to evaluate the effect of Chinese herbs on
      VSCs in vitro. METHODS: Saliva samples from volunteers were used as the source
      for the evaluation of bacterial activity and VSC inhibition. Extracted substances
      from Chinese herbs were identified by VSC inhibition tests with a Halimeter and
      microbial sensitivity testing. The effectiveness on halitosis was compared
      between a dentifrice containing one of the effective Chinese herbs (ie,
      chrysanthemum flower [Chrysanthemum morifolium flos]), 4 commercially available
      antihalitosis dentifrices, and a positive control that received no treatment.
      RESULTS: Ten volunteers provided saliva samples for VSC testing. Of the 40 herbs
      tested, 14 extracts had percent inhibition rates of VSCs >50%. Ten herbs showed
      greatest effect against all culturable microorganisms with bacterial inhibition
      >70%. There was a weak positive correlation between bacteriostasis and the anti
      VSC activity of the herbs with a correlation coefficient of 0.2579 (Pearson). The
      mean (SD) values of the VSC testing were as follows: dentifrice containing
      chrysanthemum flower, 55.91 (8.16) ppb; Crest Tea Refreshing Dentifrice(r), 48.39
      (7.48) ppb (P = NS); Cortex Phellodendri Dentifrice(r), 139.90 (14.70) ppb (P <
      0.01); Colgate Total Plus Whitening(r), 120.94 (15.58) ppb (P < 0.01); Zhong Hua
      Chinese Herbs Dentifrice(r), 136.96 (13.06) ppb (P < 0.01); and positive control,
      312.38 (28.58) ppb (P < 0.01). CONCLUSIONS: Of 40 herbs tested, 14 Chinese herbs
      were found to be effective for VSC inhibition. A dentifrice containing
      chrysanthemum flower reduced the formation of VSC in vitro, showing a
      significantly greater effect than the control group and 3 of 4 dentifrices
      already on the market.

PMID- 24683261
TI  - Effects of dibutyryl cyclic adenosine monophosphate on hypercapnic depression of
      diaphragmatic contractility in pentobarbital-anesthetized dogs.
AB  - BACKGROUND: Hypercapnia is associated with diaphragm muscle dysfunction that
      causes a reduction of diaphragmatic force generated for a constant elective
      myographic activity. No published data are available concerning hypercapnic
      depression of diaphragmatic contractility during dibutyryl cyclic adenosine
      monophospate (DBcAMP) administration. OBJECTIVE: The aim of this study was to
      assess the effects of DBcAMP on hypercapnic depression of diaphragmatic
      contractility in pentobarbital-anesthetized dogs. METHODS: This experimental
      study was conducted from July to December 2008 at the Department of
      Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba,
      Japan. Adult (aged >5 years) mongrel dogs weighing 10 to 15 kg were randomly
      divided into 3 equal groups. Hypercapnia (80-90 mm Hg) was induced with 10%
      carbon dioxide added to the inspired gas. When hypercapnia was established, group
      1 was infused with low-dose DBcAMP (0.05 mg/kg/min); group 2 was infused with
      high-dose DBcAMP (0.2 mg/kg/min); and group 3 received placebo (saline). Study
      drug was administered intravenously for 60 minutes. Diaphragmatic contractility
      was assessed by transdiaphragmatic pressure (Pdi) at baseline, induction of
      hypercapnia, and study drug administration. RESULTS: Twenty-one dogs were divided
      into 3 groups of 7. There were no significant differences observed at baseline.
      In the presence of hypercapnia, Pdi (mean [SD], cm H2O) at low- (20-Hz) and high
      frequency (100-Hz) stimulation was significantly decreased from baseline in each
      group (all, P = 0.001). In groups 1 and 2, Pdi at both stimuli was significantly
      increased during DBcAMP administration compared with hypercapnia-induced values
      (group 1: 20-Hz, 13.5 [2.2] vs 15.0 [2.4], respectively, P = 0.001, 100-Hz, 21.2
      [1.6] vs 22.5 [1.6], P = 0.001; group 2: 20-Hz, 13.7 [1.4] vs 19.2 [1.7], P =
      0.001, 100-Hz, 21.0 [2.4] vs 27.2 [2.5], P = 0.001). The Pdi at both stimuli
      during DBcAMP administration was significantly higher in group 2 than in group 1
      (20-Hz, 19.2 [1.7] vs 15.0 [2.4], P = 0.001, 100-Hz, 27.2 [2.5] vs 22.5 [1.6], P
      = 0.003). In group 3, Pdi did not significantly change in regard to either
      stimulus from hypercapnia-induced values. CONCLUSION: DBcAMP, in a dose-dependent
      manner, was associated with improved hypercapnic depression of diaphragmatic
      contractility in these pentobarbital-anesthetized dogs.

PMID- 24683260
TI  - Sedation during noninvasive mechanical ventilation with dexmedetomidine or
      midazolam: A randomized, double-blind, prospective study.
AB  - BACKGROUND: Effective noninvasive mechanical ventilation (NIV) requires a patient
      to be comfortable and in synch with the ventilator, for which sedation is usually
      needed. Choice of the proper drug for sedation can lead to improved clinical
      outcomes. OBJECTIVE: The aim of this study was to compare the effectiveness of
      dexmedetomidine and midazolam on sedation and their effects on hemodynamics and
      gas exchange. METHODS: In this randomized, double-blind study, intensive care
      unit patients with acute respiratory failure due to acute exacerbations of
      chronic obstructive pulmonary disease undergoing NIV were equally randomized to
      receive a loading dose of 1 MUg/kg IV dexmedetomidine or 0.05 MUg/kg midazolam
      over 10 minutes followed by a maintenance infusion of 0.5 MUg/kg/h
      dexmedetomidine (group D) or 0.1 mg/kg/h midazolam (group M). The following
      parameters were measured by a blinded clinician at baseline and 1, 2, 4, 6, 8,
      12, and 24 hours after the loading dose was administered: Ramsay Sedation Score
      (RSS), Riker Sedation-Agitation Scale (RSAS), Bispectral Index (BIS), arterial
      blood gases, and vital signs. A second blinded investigator determined dosing
      changes according to the outcome of maintaining a target sedation level of RSS 2
      to 3, RSAS 3 to 4, and BIS >85. RESULTS: A total of 45 patients were assessed for
      enrollment in the study; 4 did not meet the inclusion criteria and 1 refused to
      participate (men/women 19/21; mean age 58/60; all patients were receiving
      bronchodilators, steroids, antibiotics, and mucolytics). In both groups (n = 20),
      RSS significantly increased and RSAS levels and BIS values significantly
      decreased after the loading dose, compared with baseline (P < 0.05). RSS levels
      were significantly lower beginning at 4 hours in group D compared with group M (P
      < 0.05). RSAS levels were not significantly different between the 2 groups in the
      first 8 hours. However, RSAS levels were significantly higher at 8 hours after
      the loading dose was administered in group D compared with group M (P < 0.01).
      BIS was significantly higher in group D throughout the study period (P < 0.05).
      Respiratory rates and gas exchange values were not significantly different
      between the Accepted for publication April 7, 2010. 2 groups. The number of times
      a change in infusion dose was needed was significantly lower in group D (2
      patients with 1 change each) than in group M (3 patients with 1 change, 1 patient
      with 2 changes, and 3 patients with 3 changes each) (P < 0.01). CONCLUSIONS:
      Dexmedetomidine and midazolam are both effective sedatives for patients with NIV.
      Dexmedetomidine required fewer adjustments in dosing compared with midazolam to
      maintain adequate sedation.

PMID- 24683262
TI  - Effects of a histone deacetylase inhibitor, sodium butyrate, on 53-kDa protein
      expression and sensitivity to anticancer drugs of pancreatic cancer cells.
AB  - BACKGROUND: Several tumor-suppressor genes, such as 53-kDa protein (p53), are
      inactivated in some pancreatic cancers. The lack of a functional p53 has been
      proposed to be a component of resistance to chemotherapy, resulting in the
      inhibition of apoptosis. Therefore, reintroduction of wild-type p53 is a commonly
      used gene therapy strategy for the treatment of various types of cancer,
      including pancreatic cancer. OBJECTIVE: The aim of this study was to examine the
      ability of the histone deacetylase inhibitor, sodium butyrate (NaB), to modulate
      the expression of p53. METHODS: Five human pancreatic carcinoma cell lines (SW
      1990, BxPC-3, PANC-1, MIA PaCa-2, JHP-1) were utilized. Two of the cell lines (SW
      1990 and JHP-1) lacked p53 expression, as determined by Western blot analysis,
      and were investigated further. Expression of p53 was determined by densitometry
      of all bands present in the Western blot. Drug sensitivity was measured with a
      tetrazolium-based assay by exposing the cells to graded concentrations of NaB
      and/or anticancer drugs (cisplatin, fluorouracil, SN-38, and paclitaxel).
      Apoptosis was observed using gel electrophoresis. RESULTS: In the SW-1990 and JHP
      1 cell lines, use of 1 mM NaB was found to induce histone acetylation and p53
      expression compared with those not treated with NaB (P = 0.01 and P = 0.018,
      respectively). Sensitivity to cisplatin (P = 0.021), fluorouracil (P = 0.046),
      and SN-38 (P = 0.039) was significantly enhanced by NaB treatment compared with
      nontreatment. However, sensitivity to paclitaxel was not significantly different
      between untreated and NaB-treated cells. A higher frequency of apoptosis was
      observed in NaB-treated cells compared with that of control cells. CONCLUSION:
      This in vitro study found that NaB induced p53 expression in 2 pancreatic cancer
      cell lines (SW-1990 and JHP-1). Moreover, NaB acted on a biochemical modulator
      for antieuplastic therapy. Future research is necessary to assess the value of
      these findings.

PMID- 24683263
TI  - Effects of photodynamic therapy with verteporfin for the treatment of chronic
      central serous chorioretinopathy: An uncontrolled, open-label, observational
      study.
AB  - BACKGROUND: Central serous chorioretinopathy is an idiopathic disorder that leads
      to serous neurosensory retinal detachment. The disorder is usually self-limited
      and resolves spontaneously; however, sometimes neurosensory retinal detachment
      persists. This form of the disorder is called chronic central serous
      chorioretinopathy (CCSC). OBJECTIVE: The aim of this study was to assess the
      effects of photodynamic therapy (PDT) on visual acuity with full-dose verteporfin
      for CCSC. METHODS: The eyes of patients with CCSC were included in the study.
      Ophthalmic examination including best-corrected visual acuity (BCVA), fundus
      examination, fluorescein angiography, and optical coherence tomography was
      performed before treatment and at 1, 3, 6, 9, and 12 months. PDT with full-dose
      verteporfin (6 MU/m(2) of body surface area) was applied only to areas of active
      leakage. BCVA was converted to a log of the minimum angle of resolution (logMAR)
      equivalent for statistical analysis. Central foveal thickness and BCVA between
      baseline and follow-up were compared. RESULTS: Seventeen eyes of 16 patients (13
      males, 3 females; mean [SD] age, 39.75 [7.51] years; mean duration of follow-up,
      13.06 [1.82] months) were used in the study. The mean (SEM) logMAR BCVA was 0.26
      (0.07) at baseline and 0.04 (0.02) at 12 months. Mean logMAR BCVA values at
      baseline (0.259) and after treatment (0.112, 0.053, 0.047, 0.041, and 0.041 at 1,
      3, 6, 9, and 12 months, respectively) differed significantly (P = 0.006, P =
      0.005, P = 0.005, P = 0.005, and P = 0.005). There was a significant difference
      in the mean central foveal thickness at the final visit (169 MUm) compared with
      the baseline value (383 MUm; P < 0.001). BCVA decreased in one eye (20/20 vs
      20/25) and persisted during follow-up; in the other 16 eyes, BCVA either
      increased (n = 10) or remained stable (n = 6). CONCLUSIONS: In this small, open
      label study, patients with CCSC treated with a single course of PDT with full
      dose verteporfin had significant improvement from baseline in BCVA and resolution
      of subretinal fluid accumulation and active leakage. Treatment was generally well
      tolerated, but one patient had worsening in BCVA.

PMID- 24683264
TI  - Effects of doxycycline on intestinal ischemia reperfusion injury induced by
      abdominal compartment syndrome in a rat model.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and
      ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut
      results in the triggering of a systemic inflammatory response by releasing
      cytokines which, in turn, causes capillary leakage leading to bowel edema,
      further increasing intra-abdominal pressure and resulting in a morbid cycle of
      ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects
      of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of
      ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1
      and 2, saline (1 cc IP) was administered during induction of ACS and intestinal
      samples were removed at 1 and 24 hours, respectively, after decompression. In
      groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS
      and, similarly, intestinal samples were removed at 1 and 24 hours after
      decompression. In the control group (group 5), intestinal samples were collected
      without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1beta, IL-6,
      tumor necrosis factor (TNF)-alpha, matrix metalloproteinase-2 (MMP-2), and tissue
      inhibitor of metalloproteinase-1 were studied and the apoptotic cells were
      enumerated histopathologically. Apoptosis and beta-cell lymphoma 2 (betacl-2)
      expression were assessed immunohistochemically. RESULTS: Thirty-five rats were
      evenly divided into 5 groups of 7 rats each. MDA, IL-1beta, IL-6, TNF-alpha, and
      MMP-2 levels were significantly higher in group 1 one hour after the reperfusion
      period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P <
      0.001, and P < 0.01, respectively). The same parameters were significantly lower
      in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P
      < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no
      significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05).
      The mean (SD) number of apoptotic cells and the expression of betacl-2 was
      highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9
      [5.0], respectively) and significantly greater than that in group 4 (P < 0.001
      and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with
      protective effects against I/R injury through decreasing apoptosis via
      attenuating the response of proinflammatory cytokines and inhibiting the activity
      of MMP-2 in this rat model.

PMID- 24683265
TI  - Are Minority Children Disproportionately Represented in Early Intervention and
      Early Childhood Special Education?
AB  - We investigated whether and to what extent children who are racial/ethnic
      minorities are disproportionately represented in early intervention and/or early
      childhood special education (EC/ECSE). We did so by analyzing a large sample of
      48-month-olds (N=7,950) participating in the Early Childhood Longitudinal Study
      Birth Cohort (ECLS-B), a nationally representative dataset of children born in
      the U.S. in 2001. Multivariate logistic regression analyses indicate that boys
      (OR=1.66), children born at very low birthweight (OR=3.98) or with congenital
      anomalies (OR=2.17), and children engaging in externalizing problem behaviors
      (OR=1.10) are more likely to be represented in EI/ECSE. Children from low SES
      households (OR=.48), those displaying greater numeracy or receptive language
      knowledge (ORs=.96 and .76, respectively), and children being raised in
      households where a language other than English is primarily spoken (OR=.39) are
      less likely to be represented in EI/ECSE. Statistical control for these and an
      extensive set of additional factors related to cognitive and behavioral
      functioning indicated that 48-month-old children who are Black (OR=.24) or Asian
      (OR=.32) are disproportionately under-represented in EI/ECSE in the U.S.

PMID- 24683266
TI  - Assembly of crosslinked oxo-cyanoruthenate and zirconium oxide bilayers:
      Application in electrocatalytic films based on organically modified silica with
      templated pores.
AB  - Electrochemical deposition of crosslinked oxo-cyanoruthenate, Ru-O/CN-O, from a
      mixture of RuCl3 and K4Ru(CN)6 is known to yield a film on glassy carbon that
      promotes oxidations by a combination of electron and oxygen transfer. Layer-by
      layer (LbL) deposition of this species and of a film formed by cycling of the
      electrode potential in a ZrO2 solution systematically increases the number of
      catalytically active sites of the Ru-O/CN-O on the electrode. The evaluation of
      the electrocatalytic activity was by cyclic voltammetric oxidation of cysteine at
      pH 2. Plots of the anodic peak current vs. the square root of scan rate were
      indicative of linear diffusion control of this oxidation, even in the absence of
      ZrO2, but the slopes of these linear plots increased with bilayer number, n, of
      (ZrO2 | Ru-O/CN-O) n . The latter observation is hypothesized to be due to an
      increased number of active sites for a given geometric electrode area, but proof
      required further study. To optimize utilization of the catalyst and to provide a
      size-exclusion characteristic to the electrode, the study was extended to LbL
      deposition of the composite in 50-nm pores of an organically modified silica film
      deposited by electrochemically assisted sol-gel processing using surface-bound
      poly(styrene sulfonate) nanospheres as a templating agent.

PMID- 24683267
TI  - Seasonal phenology of the cerambycid beetles of east-central Illinois.
AB  - We summarize field data on the species composition and seasonal phenology of the
      community of cerambycid beetles of east-central Illinois. Data were drawn from
      field bioassays conducted during 2009 - 2012 that tested attraction of adult
      beetles of diverse species to a variety of synthetic pheromones and host plant
      volatiles. A total of 34,086 beetles of 114 species were captured, including 48
      species in the subfamily Cerambycinae, 41 species in the Lamiinae, 19 species in
      the Lepturinae, two species in the Spondylidinae, and one species each in the
      Necydalinae, Parandrinae, Prioninae, and the Disteniidae. Most of the best
      represented species were attracted to pheromones that were included in field
      experiments, particularly species that use (R)-3-hydroxyhexan-2-one as a
      pheromone component. The species captured, and their patterns of abundance and
      seasonal phenology were similar to those in an earlier study conducted in
      Pennsylvania. The most abundant species identified in both studies included the
      cerambycines Elaphidion mucronatum (Say), Neoclytus a. acuminatus (F.), Neoclytus
      m. mucronatus (F.), and Xylotrechus colonus (F.). Cerambycine species became
      active in an orderly progression from early spring through late fall, whereas
      most lamiine species were active in summer and fall, and lepturine species were
      limited to summer. Potential cross attraction between some cerambycine species
      that shared pheromone components may have been averted by differences in seasonal
      activity period, and by minor pheromone components that acted as synergists for
      conspecifics and/or antagonists for heterospecifics. These results provide
      quantitative data on the abundance and seasonal phenology of a large number of
      species.

PMID- 24683268
TI  - Spatial variation of phytoplankton composition, biovolume, and resulting
      microcystin concentrations in the Nyanza Gulf (Lake Victoria, Kenya).
AB  - The Nyanza Gulf is a large shallow bay of Lake Victoria suffering from
      eutrophication by human activities. In order to characterize the harmful algal
      bloom formation as a consequence of eutrophication, both spatially and
      seasonally, environmental conditions, phytoplankton community composition, and
      microcystin (MC) concentrations were investigated monthly from Kisumu Bay, and
      bimonthly from the center of the gulf, as well as quarterly from the Rusinga
      Channel and the main basin of Lake Victoria between July 2008 to September 2009.
      The sites located in Kisumu Bay and the central gulf were most strongly affected
      by eutrophication, including increased nutrient concentrations and phytoplankton
      growth. More than 90% of the samples obtained from the gulf were dominated by
      cyanobacteria, whereas diatoms only dominated in the samples obtained from
      Rusinga Channel and the main lake. In general Microcystis accounted for the
      largest part (> 50-90%) of cyanobacterial biovolume. MCs were found in 35 (54%)
      out of 65 samples and were detected throughout the study period in the gulf, but
      only in two out of eight samples from the Rusinga Channel and the main lake. A
      significant linear relationship between Microcystis biovolume and MC
      concentration was observed (n = 65, R2 = 0.88, p <0.001). Highest MC
      concentrations were recorded in Kisumu Bay between November and March (max. 81
      MUg l-1) when Microcystis showed max. biovolume (18 mm3 l-1 in November 2008).
      The results suggest that seasonal variability did not outweigh the spatial
      differences in phytoplankton composition and MC production that is seasonally
      persistent in Kisumu Bay.

PMID- 24683269
TI  - Natural gas and CO2 price variation: impact on the relative cost-efficiency of
      LNG and pipelines.
AB  - THIS ARTICLE DEVELOPS A FORMAL MODEL FOR COMPARING THE COST STRUCTURE OF THE TWO
      MAIN TRANSPORT OPTIONS FOR NATURAL GAS: liquefied natural gas (LNG) and
      pipelines. In particular, it evaluates how variations in the prices of natural
      gas and greenhouse gas emissions affect the relative cost-efficiency of these two
      options. Natural gas is often promoted as the most environmentally friendly of
      all fossil fuels, and LNG as a modern and efficient way of transporting it. Some
      research has been carried out into the local environmental impact of LNG
      facilities, but almost none into aspects related to climate change. This paper
      concludes that at current price levels for natural gas and CO2 emissions the
      distance from field to consumer and the volume of natural gas transported are the
      main determinants of transport costs. The pricing of natural gas and greenhouse
      emissions influence the relative cost-efficiency of LNG and pipeline transport,
      but only to a limited degree at current price levels. Because more energy is
      required for the LNG process (especially for fuelling the liquefaction process)
      than for pipelines at distances below 9100 km, LNG is more exposed to variability
      in the price of natural gas and greenhouse gas emissions up to this distance. If
      the prices of natural gas and/or greenhouse gas emission rise dramatically in the
      future, this will affect the choice between pipelines and LNG. Such a price
      increase will be favourable for pipelines relative to LNG.

PMID- 24683270
TI  - Perceptions of Equity, Balance of Support Exchange, and Mother-Adult Child
      Relations.
AB  - Equity theory suggests that relationships are more harmonious when both members
      of a dyad believe that their exchanges are fair. However, the level and frequency
      of exchange, rather than perceptions of equity, have been the focus of most
      research on support and the quality of intergenerational relations. Using data
      from 1,426 mother-child dyads nested within 413 families collected as part of the
      Within-Family Differences Study, the authors explored whether mothers'
      perceptions of equity are better predictors of closeness and tension than are
      mothers' reports of balanced exchanges of support. Mixed-model analyses revealed
      that mothers' perceptions of equity were more consistent predictors of
      relationship quality than were the balanced exchanges of support, though the
      results varied somewhat by gender of adult child. These findings contribute to a
      growing body of research demonstrating that the psychological processes that
      shape intergenerational relationships mirror those of other ties.

PMID- 24683271
TI  - Revisiting Williams on Integrity.

PMID- 24683273
TI  - In-Situ Optical Coherence Tomography (OCT) for the Time-Resolved Investigation of
      Crystallization Processes in Polymers.
AB  - By application of optical coherence tomography (OCT), an interferometric
      noncontact imaging technique, the crystallization of a supercooled
      poly(propylene) melt in a slit die is monitored. Both the quiescent and the
      sheared melt are investigated, with a focus on experiments where solidification
      and flow occur simultaneously. OCT is found to be an excellent tool for that
      purpose since the resultant structures are strongly scattering, which is a
      prerequisite for application of that method. The resulting images enable for the
      first time to directly monitor structure development throughout the whole
      experiment, including final cooling to room temperature. By rendering the setup
      polarization-sensitive, information on the birefringence of the pertinent
      structures is obtained.

PMID- 24683272
TI  - Presentation of large DNA molecules for analysis as nanoconfined dumbbells.
AB  - The analysis of very large DNA molecules intrinsically supports long-range,
      phased sequence information, but requires new approaches for their effective
      presentation as part of any genome analysis platform. Using a multi-pronged
      approach that marshaled molecular confinement, ionic environment, and DNA elastic
      properties-but tressed by molecular simulations-we have developed an efficient
      and scalable approach for presentation of large DNA molecules within nanoscale
      slits. Our approach relies on the formation of DNA dumbbells, where large
      segments of the molecules remain outside the nanoslits used to confine them. The
      low ionic environment, synergizing other features of our approach, enables DNA
      molecules to adopt a fully stretched conformation, comparable to the contour
      length, thereby facilitating analysis by optical microscopy. Accordingly, a
      molecular model is proposed to describe the conformation and dynamics of the DNA
      molecules within the nanoslits; a Langevin description of the polymer dynamics is
      adopted in which hydrodynamic effects are included through a Green's function
      formalism. Our simulations reveal that a delicate balance between electrostatic
      and hydrodynamic interactions is responsible for the observed molecular
      conformations. We demonstrate and further confirm that the "Odijk regime" does
      indeed start when the confinement dimensions size are of the same order of
      magnitude as the persistence length of the molecule. We also summarize current
      theories concerning dumbbell dynamics.

PMID- 24683274
TI  - Physicochemical Evaluation of an Experimental Endodontic Sealer.

PMID- 24683275
TI  - Probabilistic Polling And Voting In The 2008 Presidential Election: Evidence From
      The American Life Panel.
AB  - This article reports new empirical evidence on probabilistic polling, which asks
      persons to state in percent-chance terms the likelihood that they will vote and
      for whom. Before the 2008 presidential election, seven waves of probabilistic
      questions were administered biweekly to participants in the American Life Panel
      (ALP). Actual voting behavior was reported after the election. We find that
      responses to the verbal and probabilistic questions are well-aligned ordinally.
      Moreover, the probabilistic responses predict voting behavior beyond what is
      possible using verbal responses alone. The probabilistic responses have more
      predictive power in early August, and the verbal responses have more power in
      late October. However, throughout the sample period, one can predict voting
      behavior better using both types of responses than either one alone. Studying the
      longitudinal pattern of responses, we segment respondents into those who are
      consistently pro-Obama, consistently anti-Obama, and undecided/vacillators.
      Membership in the consistently pro- or anti-Obama group is an almost perfect
      predictor of actual voting behavior, while the undecided/vacillators group has
      more nuanced voting behavior. We find that treating the ALP as a panel improves
      predictive power: current and previous polling responses together provide more
      predictive power than do current responses alone.

PMID- 24683276
TI  - An inconvenient dataset: bias and inappropriate inference with the multilevel
      model.
AB  - The multilevel model has become a staple of social research. I textually and
      formally explicate sample design features that, I contend, are required for
      unbiased estimation of macro-level multilevel model parameters and the use of
      tools for statistical inference, such as standard errors. After detailing the
      limited and conflicting guidance on sample design in the multilevel model
      didactic literature, illustrative nationally-representative datasets and
      published examples that violate the posited requirements are identified. Because
      the didactic literature is either silent on sample design requirements or in
      disagreement with the constraints posited here, two Monte Carlo simulations are
      conducted to clarify the issues. The results indicate that bias follows use of
      samples that fail to satisfy the requirements outlined; notably, the bias is
      poorly-behaved, such that estimates provide neither upper nor lower bounds for
      the population parameter. Further, hypothesis tests are unjustified. Thus,
      published multilevel model analyses using many workhorse datasets, including
      NELS, AdHealth, NLSY, GSS, PSID, and SIPP, often unwittingly convey substantive
      results and theoretical conclusions that lack foundation. Future research using
      the multilevel model should be limited to cases that satisfy the sample
      requirements described.

PMID- 24683277
TI  - High School Transfer Students and the Transition to College: Timing and the
      Structure of the School Year.
AB  - The timing of a high school transfer may shape students' transitions to college
      through its (mis)alignment with the structure of the school year. A transfer that
      occurs during the summer interrupts the four-year high school career, whereas a
      transfer that occurs midyear disrupts both the four-year high school career and
      the structure of the school year. Using the Education Longitudinal Study of 2002
      (ELS), the investigators find that the penalty suffered after the transfer
      depends on the degree to which students' high school pathways synchronize with
      the curricular and extracurricular structure of the school year. Midyear transfer
      students appear to suffer the greatest postsecondary matriculation penalty.
      Students who transfer midyear are less likely to attend a four-year college
      compared with nontransfer and summer transfer students, whereas summer transfer
      students are less likely to attend a highly selective four-year college compared
      with their nontransfer counterparts. Curricular and extracurricular disruptions
      that transfer students experience after their school move explain some, but not
      all, of the negative associations observed between transferring and the
      transition to college. Directions for future research and the theoretical and
      policy implications of the results are discussed.

PMID- 24683278
TI  - Local Fluctuations in Solution: Theory and Applications.

PMID- 24683279
TI  - Designing Work, Family & Health Organizational Change Initiatives.
AB  - For decades, leaders and scholars have been advocating change efforts to improve
      work-life relationships. Yet most initiatives have lacked rigor and not been
      developed using scientific principles. This has created an evidence gap for
      employer support of work and personal life as a win-win for productivity and
      employees' well-being. This paper examines the approach used by the U.S. Work
      Family Health Network (WFRN) to develop an innovative workplace intervention to
      improve employee and family health. The change initiative was designed to reduce
      organizationally based work-family conflict in two contrasting contexts
      representative of major segments of today's U.S. workforce: health care employees
      and informational technology professionals. The WFRN Intervention (called STAR)
      had three theoretically based change elements. They were: 1) increase job control
      over work time and schedule; 2) increase supervisor social support for family and
      job effectiveness; and 3) improve organizational culture and job design processes
      to foster results orientation. Seven practical lessons for developing work-life
      interventions emerged from this groundbreaking endeavor.

PMID- 24683280
TI  - Assessing the Stages of Change Among African American Women in a Weight
      Management Program.
AB  - The objective of this study was to assess the relationship between stage of
      change (SOC) and behavioral outcomes among African American women entering
      obesity treatment in two settings. Fifty-five overweight/obese (body mass index =
      26.50-48.13), but otherwise healthy African American women, 23 to 56 years old,
      attended a 13-week weight loss-treatment program that took place at churches (n =
      36) or a university (n = 19). Participants were weighed, completed SOC measures,
      and had a physical fitness test at pre- and posttreatment. Pretreatment measures
      of SOC placed 47% of the participants as actors, 31% as contemplators, and 22% as
      maintainers. Of the 45 women who reported posttreatment SOC, 7% regressed, 44%
      did not change, and 31% progressed in SOC. Pretreatment SOC predicted
      posttreatment weight loss in the church setting but not in the university
      setting. At churches, contemplators lost more weight than actors and maintainers.
      The church may be a more conducive setting for weight change behaviors for
      African American women who are categorized as contemplators in the SOC model.

PMID- 24683281
TI  - A new estimation approach for combining epidemiological data from multiple
      sources.
AB  - We propose a novel two-step procedure to combine epidemiological data obtained
      from diverse sources with the aim to quantify risk factors affecting the
      probability that an individual develops certain disease such as cancer. In the
      first step we derive all possible unbiased estimating functions based on a group
      of cases and a group of controls each time. In the second step, we combine these
      estimating functions efficiently in order to make full use of the information
      contained in data. Our approach is computationally simple and flexible. We
      illustrate its efficacy through simulation and apply it to investigate pancreatic
      cancer risks based on data obtained from the Connecticut Tumor Registry, a
      population-based case-control study, and the Behavioral Risk Factor Surveillance
      System which is a state-based system of health surveys.

PMID- 24683282
TI  - Determining directional dependency in causal associations.
AB  - Directional dependency is a method to determine the likely causal direction of
      effect between two variables. This article aims to critique and improve upon the
      use of directional dependency as a technique to infer causal associations. We
      comment on several issues raised by von Eye and DeShon (2012), including:
      encouraging the use of the signs of skewness and excessive kurtosis of both
      variables, discouraging the use of D'Agostino's K2, and encouraging the use of
      directional dependency to compare variables only within time points. We offer
      improved steps for determining directional dependency that fix the problems we
      note. Next, we discuss how to integrate directional dependency into longitudinal
      data analysis with two variables. We also examine the accuracy of directional
      dependency evaluations when several regression assumptions are violated.
      Directional dependency can suggest the direction of a relation if (a) the
      regression error in population is normal, (b) an unobserved explanatory variable
      correlates with any variables equal to or less than .2, (c) a curvilinear
      relation between both variables is not strong (standardized regression
      coefficient <= .2), (d) there are no bivariate outliers, and (e) both variables
      are continuous.

PMID- 24683283
TI  - Assumptions regarding right censoring in the presence of left truncation.
AB  - Clinical studies using complex sampling often involve both truncation and
      censoring, where there are options for the assumptions of independence of
      censoring and event and for the relationship between censoring and truncation. In
      this paper, we clarify these choices, show certain equivalences, and provide
      examples.

PMID- 24683284
TI  - Intrusive Thoughts Mediate the Association between Neuroticism and Cognitive
      Function.
AB  - Although research has established a negative association between trait
      neuroticism and cognition, little is known about the mechanisms that underlie
      this relationship. We examined the tendency to experience intrusive thoughts and
      negative affect as potential mediators of the relationship between neuroticism
      and cognitive performance. We hypothesized that the tendency to experience
      intrusive thoughts reflects ineffective attentional control and would account for
      the relationship between neuroticism and cognitive performance over and above the
      mediating effect of negative affect. Three hundred seventeen adults (Mage =49.43)
      completed a series of attention-demanding cognitive tasks as well as self-report
      measures of intrusive thoughts, negative affect, and neuroticism. Intrusive
      thoughts mediated the association between trait neuroticism and cognitive
      performance beyond negative affect. These findings are consistent with the
      hypothesis that the tendency to experience intrusive thoughts is a mechanism
      through which trait neuroticism influences cognitive performance.

PMID- 24683285
TI  - The Association Between Lifestyle Activities and Late-Life Depressive Symptoms.
AB  - The association between lifestyle activities and incident depressive symptoms was
      examined within the Women's Health and Aging Study II. Measures of activity and
      depressive symptoms were collected on four occasions, spanning six-years.
      Discrete-time Cox proportional hazards models were employed to examine the
      effects of baseline activity on depressive symptoms over time. Overall, activity
      was not associated with incident depressive symptoms. When specific activity
      domains were examined, greater participation in creative activities was
      associated with a reduced risk of depressive symptoms (hazard ratio = 0.92; CI
      95% 0.87, 0.98). Further longitudinal research between diverse activities and
      incident depressive symptoms is warranted.

PMID- 24683286
TI  - Effects of Verb Bias and Syntactic Ambiguity on Reading in People with Aphasia.
AB  - BACKGROUND: The Lexical Bias Hypothesis (Gahl, 2002) claims that people with
      aphasia have difficulty understanding sentences when the verb's argument
      structure bias conflicts with the sentence structure. This hypothesis can account
      for comprehension deficits that affect simple sentences, but the role of verb
      bias has not been clearly demonstrated in temporarily ambiguous sentences. AIMS:
      This study examined how verb bias affects comprehension of temporarily ambiguous
      and unambiguous sentences using self-paced reading. METHODS & PROCEDURES: People
      with aphasia and controls read sentences that contained sentential complements
      (e.g., The talented photographer accepted (that) the fire could not have been
      prevented.). The main verb was biased to take a direct object (e.g., accepted) or
      a sentential complement (e.g., admitted). In addition, the sentential complement
      was either introduced by the complementizer that (i.e., unambiguous) or unmarked
      (i.e., ambiguous). RESULTS: The people with aphasia's reading times were affected
      more by verb bias than by the presence of the complementizer, whereas the control
      group's reading times were more affected by the presence or absence of the
      complementizer. CONCLUSIONS: The results were generally consistent with the
      Lexical Bias Hypothesis, and showed that a mismatch between verb bias and
      sentence structure affected processing of unambiguous and temporarily ambiguous
      sentences in people with aphasia.

PMID- 24683287
TI  - Synthesis and Characterization of Arsenolipids: Naturally Occurring Arsenic
      Compounds in Fish and Algae.
AB  - Arsenic-containing lipids (arsenolipids) are natural products present in fish and
      algae. Because these compounds occur in foods, there is considerable interest in
      their human toxicology. We report the synthesis and characterization of seven
      arsenic-containing lipids, including six natural products. The compounds comprise
      dimethylarsinyl groups attached to saturated long-chain hydrocarbons (three
      compounds), saturated long-chain fatty acids (two compounds), and monounsaturated
      long chain fatty acids (two compounds). The arsenic group was introduced through
      sodium dimethylarsenide or bis(dimethylarsenic) oxide. The latter route provided
      higher and more reproducible yields, and consequently, this pathway was followed
      to synthesize six of the seven compounds. Mass spectral properties are described
      to assist in the identification of these compounds in natural samples. The pure
      synthesized arsenolipids will be used for in vitro experiments with human cells
      to test their uptake, biotransformation, and possible toxic effects.

PMID- 24683288
TI  - Validation of a Brief Yesterday Measure of Hedonic Well-Being and Daily
      Activities: Comparison with the Day Reconstruction Method.
AB  - There has been increasing interest in the measurement of hedonic well-being
      (HWB), due in part to its broad implications in areas such as health and society.
      The day reconstruction method (DRM) is a validated technique assessing HWB and
      daily activities using instructions that help respondents recover their
      experiences from the previous day, thus reducing recall bias. Unfortunately,
      large-scale surveys are typically not able to implement the time-consuming DRM
      procedure; instead, they rely on single-item or very brief questionnaire
      assessment of HWB and time usage. Despite their wide use, brief questionnaires
      have rarely been compared to the DRM, which could provide validation of these
      short assessments. In the present study we compared these two questionnaire
      formats in 45 adults who completed both a DRM and a "hybrid" short form (HSF)
      questionnaire that included a very brief procedure to reconstruct yesterday's
      events. Results were that the mean HSF ratings tended to overestimate HWB in
      comparison to the DRM, though effects were generally small to moderate. With
      regard to estimates of time spent on daily activities, the HSF also differed from
      the DRM, though with generally small to moderate effects. Correlations between
      estimates indicated that the HSF explained an average of almost half the variance
      in the DRM ratings for both HWB (rs ranging from .52 to .97) and time use (rs
      ranging from .43 to .85). In general, HSF ratings displayed considerable overlap
      with those of the DRM though the brief instructions apparently did not eliminate
      recall bias in the shorter questionnaire.

PMID- 24683289
TI  - On the estimation of a binary response model in a selected population.
AB  - A generalization of the Probit model is presented, with the extended skew-normal
      cumulative distribution as a link function, which can be used for modelling a
      binary response variable in the presence of selectivity bias. The estimate of the
      parameters via ML is addressed, and inference on the parameters expressing the
      degree of selection is discussed. The assumption underlying the model is that the
      selection mechanism influences the unmeasured factors and does not affect the
      explanatory variables. When this assumption is violated, but other conditional
      independencies hold, then the model proposed here is derived. In particular, the
      instrumental variable formula still applies and the model results at the second
      stage of the estimating procedure.

PMID- 24683290
TI  - Misperceptions in Stereoscopic Displays: A Vision Science Perspective.
AB  - 3d shape and scene layout are often misperceived when viewing stereoscopic
      displays. For example, viewing from the wrong distance alters an object's
      perceived size and shape. It is crucial to understand the causes of such
      misperceptions so one can determine the best approaches for minimizing them. The
      standard model of misperception is geometric. The retinal images are calculated
      by projecting from the stereo images to the viewer's eyes. Rays are back
      projected from corresponding retinal-image points into space and the ray
      intersections are determined. The intersections yield the coordinates of the
      predicted percept. We develop the mathematics of this model. In many cases its
      predictions are close to what viewers perceive. There are three important cases,
      however, in which the model fails: 1) when the viewer's head is rotated about a
      vertical axis relative to the stereo display (yaw rotation); 2) when the head is
      rotated about a forward axis (roll rotation); 3) when there is a mismatch between
      the camera convergence and the way in which the stereo images are displayed. In
      these cases, most rays from corresponding retinal-image points do not intersect,
      so the standard model cannot provide an estimate for the 3d percept. Nonetheless,
      viewers in these situations have coherent 3d percepts, so the visual system must
      use another method to estimate 3d structure. We show that the non-intersecting
      rays generate vertical disparities in the retinal images that do not arise
      otherwise. Findings in vision science show that such disparities are crucial
      signals in the visual system's interpretation of stereo images. We show that a
      model that incorporates vertical disparities predicts the percepts associated
      with improper viewing of stereoscopic displays. Improving the model of
      misperceptions will aid the design and presentation of 3d displays.

PMID- 24683291
TI  - Stress generation and exposure in a multi-wave study of adolescents:
      Transactional processes and sex differences.
AB  - Given considerable overlap among individual difference predictors of stress
      generation, the current study sought to elucidate which individual factors are
      uniquely involved in the stress generation process for interpersonal and
      achievement events among adolescents. Further, we examined transactional
      processes between stressors and depressive symptoms and explored potential sex
      differences in the unique prediction of stress generation. At baseline, youth
      (6th-10th graders, n=350, 57% female; 53% White) reported on various individual
      differences hypothesized to predict prospective increases in stressors. Youth
      also reported on depressive symptoms and stressors for 4 waves over 5 months.
      Multi-level modeling showed that different individual difference factors uniquely
      prospectively predicted increases in dependent (interpersonal and achievement)
      stressors. Central to this process was interpersonal vulnerabilities and
      psychopathology. Some of these predictions differed for boys and girls. In
      addition and in support of a transactional relationship between stressors and
      depressive symptoms, increases in stressors predicted prospective elevations in
      depressive symptoms for both boys and girls. This study provides support for the
      transactional nature of stress and depression in a multi-wave study of
      adolescence. This study demonstrates that particular individual factors are
      uniquely associated with the generation of stress, with some associations
      moderated by gender.

PMID- 24683292
TI  - Headship of older persons in the context of HIV/AIDS in rural South Africa.
AB  - This paper examines older persons' positions as heads of households in the
      Agincourt sub-district of Mpumalanga Province, South Africa. Older person's
      access to non-contributory pensions in a context of AIDS-related chronic illness
      and premature death, might increase their household responsibilities which, in
      turn, may be manifested in higher rates of household headship. We use descriptive
      analysis to outline the traits of household heads, compare household
      characteristics, in particular recent mortality experience, across headship types
      (male/female, pre/post-pension eligibility). While some significant differences
      in household composition exist across headship types, older persons were no more
      likely to be heading households with a HIV/AIDS-related death over the 2000-2005
      period-prior to extensive antiretroviral (ARV) rollout. This provides an
      important starting point for further investigations aimed at understanding the
      impact of HIV/AIDS on older persons' lives, and as a baseline for measuring the
      effects of ARV rollout on older persons' status in AIDS-endemic communities.

PMID- 24683293
TI  - Detecting Inappropriate Access to Electronic Health Records Using Collaborative
      Filtering.
AB  - Many healthcare facilities enforce security on their electronic health records
      (EHRs) through a corrective mechanism: some staff nominally have almost
      unrestricted access to the records, but there is a strict ex post facto audit
      process for inappropriate accesses, i.e., accesses that violate the facility's
      security and privacy policies. This process is inefficient, as each suspicious
      access has to be reviewed by a security expert, and is purely retrospective, as
      it occurs after damage may have been incurred. This motivates automated
      approaches based on machine learning using historical data. Previous attempts at
      such a system have successfully applied supervised learning models to this end,
      such as SVMs and logistic regression. While providing benefits over manual
      auditing, these approaches ignore the identity of the users and patients involved
      in a record access. Therefore, they cannot exploit the fact that a patient whose
      record was previously involved in a violation has an increased risk of being
      involved in a future violation. Motivated by this, in this paper, we propose a
      collaborative filtering inspired approach to predicting inappropriate accesses.
      Our solution integrates both explicit and latent features for staff and patients,
      the latter acting as a personalized "finger-print" based on historical access
      patterns. The proposed method, when applied to real EHR access data from two
      tertiary hospitals and a file-access dataset from Amazon, shows not only
      significantly improved performance compared to existing methods, but also
      provides insights as to what indicates an inappropriate access.

PMID- 24683295
TI  - A Conjoint Analysis Framework for Evaluating User Preferences in Machine
      Translation.
AB  - Despite much research on machine translation (MT) evaluation, there is
      surprisingly little work that directly measures users' intuitive or emotional
      preferences regarding different types of MT errors. However, the elicitation and
      modeling of user preferences is an important prerequisite for research on user
      adaptation and customization of MT engines. In this paper we explore the use of
      conjoint analysis as a formal quantitative framework to assess users' relative
      preferences for different types of translation errors. We apply our approach to
      the analysis of MT output from translating public health documents from English
      into Spanish. Our results indicate that word order errors are clearly the most
      dispreferred error type, followed by word sense, morphological, and function word
      errors. The conjoint analysis-based model is able to predict user preferences
      more accurately than a baseline model that chooses the translation with the
      fewest errors overall. Additionally we analyze the effect of using a crowd
      sourced respondent population versus a sample of domain experts and observe that
      main preference effects are remarkably stable across the two samples.

PMID- 24683294
TI  - Impact of water mass mixing on the biogeochemistry and microbiology of the
      Northeast Atlantic Deep Water.
AB  - The extent to which water mass mixing contributes to the biological activity of
      the dark ocean is essentially unknown. Using a multiparameter water mass
      analysis, we examined the impact of water mass mixing on the nutrient
      distribution and microbial activity of the Northeast Atlantic Deep Water (NEADW)
      along an 8000 km long transect extending from 62 degrees N to 5 degrees S. Mixing
      of four water types (WT) and basin scale mineralization from the site where the
      WT where defined to the study area explained up to 95% of the variability in the
      distribution of inorganic nutrients and apparent oxygen utilization. Mixing
      corrected average O2:N:P mineralization ratios of 127(+/-11):13.0(+/-0.7):1 in
      the core of the NEADW suggested preferential utilization of phosphorus compounds
      while dissolved organic carbon mineralization contributed a maximum of 20% to the
      oxygen demand of the NEADW. In conjunction with the calculated average
      mineralization ratios, our results indicate a major contribution of particulate
      organic matter to the biological activity in the NEADW. The variability in
      prokaryotic abundance, high nucleic acid containing cells, and prokaryotic
      heterotrophic production in the NEADW was explained by large scale (64-79%) and
      local mineralization processes (21-36%), consistent with the idea that deep-water
      prokaryotic communities are controlled by substrate supply. Overall, our results
      suggest a major impact of mixing on the distribution of inorganic nutrients and a
      weaker influence on the dissolved organic matter pool supporting prokaryotic
      activity in the NEADW.

PMID- 24683296
TI  - Young children's perceptions of health warning labels on cigarette packages: a
      study in six countries.
AB  - AIM: Health warning labels on cigarette packages are one way to reach youth
      thinking about initiating tobacco use. The purpose of this study was to examine
      awareness and understanding of current health warning labels among 5 and 6 year
      old children. SUBJECTS AND METHODS: Researchers conducted one-on-one interviews
      with urban and rural 5 and 6 year olds from Brazil, China, India, Nigeria,
      Pakistan, and Russia. RESULTS: Among the 2,423 participating children, 62 % were
      unaware of the health warnings currently featured on cigarette packages, with the
      lowest levels of awareness in India and the highest levels in Brazil. When shown
      the messages, the same percentage of participating children (62 %) showed no
      level of message understanding. CONCLUSION: While youth are receiving social and
      informational messages promoting tobacco use, health warning labels featured on
      cigarette packages are not effectively reaching young children with anti-smoking
      messages.

PMID- 24683297
TI  - Active Video Games and Energy Expenditure in Overweight Children.
AB  - The prevalence of overweight in children has increased significantly in recent
      years. Frequent television viewing and the playing of video games have often been
      linked to the high prevalence of overweight. The purpose of this study was to
      determine if overweight children, given access to active video games, will play
      them at an intensity that will significantly increase energy expenditure. Twenty
      three children, classified as "at risk for overweight" or "overweight,"
      participated in this study. After a 10-minute baseline period in which the
      children watched a cartoon, the participants played the Jackie Chan Fitness
      Studio(r) (Xavix, Hong Kong) games for 30 minutes while rotating through the
      games as desired and resting whenever needed. Energy expenditure significantly
      increased from a mean at baseline of 1.15 +/- 0.32 kcal/min to 4.08+/-1.18
      kcal/min during the 30-minutes that the participants were given access to the
      games (p <.001). The total energy expenditure during the 30-minute time frame was
      122.30 +/- 35.40 kcal. The energy expenditure varied between individuals, with a
      low value of 75.00 kcal to a high of 205.86 kcal. Although a modest level of
      energy expenditure, this level of exertion could contribute to an overall weight
      control program in children.

PMID- 24683298
TI  - Statistical considerations in biosimilar assessment using biosimilarity index.
AB  - When an innovative biologic product goes off patent, biopharmaceutical or
      biotechnological companies may file an application for regulatory approval of
      biosimilar products. Unlike small molecule drug products, biosimilars are not
      exact copies of their brand-name counterpart, and they are usually very sensitive
      to changes in environmental factors and have greater variabilities due to their
      complexity and sensitivity to variation in manufacturing processes. Facing these
      challenges, a biosimilarity index based on reproducibility probability is
      proposed to assess biosimilarity. In this article, we have demonstrated how to
      assess biosimilarity between the test and reference product in relative to a
      reference standard that is established in a study where reference product is
      compared with itself. Biosimilairty index approach is robust against
      biosimilarity criteria and has the advantage of allowing the assessment of the
      degree of similarity.

PMID- 24683299
TI  - Parent Engagement and School Readiness: Effects of the Getting Ready Intervention
      on Preschool Children's Social-Emotional Competencies.
AB  - RESEARCH FINDINGS: Parental engagement with children has been linked to a number
      of adaptive characteristics in preschool children, and relationships between
      families and professionals are an important contributor to school readiness.
      Furthermore, social-emotional competence is a key component of young children's
      school readiness. This study reports the results of a randomized trial of a
      parent engagement intervention (Getting Ready) designed to facilitate school
      readiness among disadvantaged preschool children, with a particular focus on
      social-emotional outcomes. Two hundred and twenty children were involved over the
      4-year study period. Statistically significant differences were observed between
      treatment and control participants in the rate of change over a 2-year period on
      teacher reports for certain interpersonal competencies (i.e., attachment,
      initiative, and anxiety/ withdrawal). In contrast, no statistically significant
      differences between groups over a 2-year period were noted for behavioral
      concerns (anger/aggression, self-control, or behavioral problems) as a function
      of the Getting Ready intervention. PRACTICE OR POLICY: The intervention appears
      to be particularly effective at building social-emotional competencies beyond the
      effects experienced as a function of participation in Head Start programming
      alone. Limitations and implications for future research are reviewed.

PMID- 24683300
TI  - Children's Postdisaster Trajectories of PTS Symptoms: Predicting Chronic
      Distress.
AB  - BACKGROUND: There are no studies of the distinct trajectories of children's
      psychological distress over the first year after a destructive natural disaster
      and the determinants of these trajectories. OBJECTIVE: We examined these issues
      using an existing dataset of children exposed to Hurricane Andrew, one of the
      most devastating natural disasters in US history. METHODS: At 3-months
      postdisaster, 568 children (55 % girls; grades 3-5) residing in areas most
      directly affected by the hurricane completed measures of hurricane exposure and
      stressors, social support, coping, and general anxiety. Children also reported
      major life events occurring since the hurricane (at 7-months) and posttraumatic
      stress (PTS) symptoms at 3-, 7-, and 10-months postdisaster. RESULTS: Latent
      growth mixture modeling identified three trajectories of PTS reactions: resilient
      (37 %), recovering (43 %), and chronic distress (20 %). Predictors of the
      trajectories were examined. Odds ratios indicated that, compared to the resilient
      trajectory, girls were more likely to be in the recovering and chronically
      distressed trajectories, as were children reporting higher anxiety and greater
      use of coping strategies that reflected poor emotion regulation. Compared to the
      recovering trajectory, children in the chronically distressed trajectory had
      greater odds of reporting high anxiety, less social support, more intervening
      life events, and greater use of poor emotion regulation strategies. CONCLUSIONS:
      Hurricane exposure may be less effective in identifying children who develop
      chronic postdisaster distress than other child (anxiety, coping) and contextual
      variables (social support, life events). Effective screening after disasters is
      critical for identifying youth most in need of limited clinical resources.

PMID- 24683301
TI  - Predictors of Initial Engagement in Child Anxiety Mental Health Specialty
      Services.
AB  - BACKGROUND: Child and family mental health services remain largely underutilized
      despite the relatively high rate of youth suffering from mental, emotional, and
      behavioral (MEB) disorders. As such, it is important to address challenges and
      examine factors related to child mental health service use and engagement,
      especially when it comes to children in need of services for anxiety. OBJECTIVE:
      Informed by the Behavioral Model of Health Services Use (BMHS), the present study
      sought to examine predictors of service use and engagement for families seeking
      assistance for their anxious children. Initial levels of engagement in culturally
      tailored services were predicted from predisposing characteristics (e.g., child
      age, ethnicity), enabling resources (e.g., Spanish services, transportation), and
      need characteristics (e.g., child clinical severity). METHOD: Participants
      included Latino (n = 126) and Caucasian (n = 116) families who presented to a
      specialty clinic due to child emotional and behavior problems related to anxiety.
      Initial service utilization and engagement was assessed along the following
      levels toward services care: (1) initiated contact and completed a clinical
      intake, (2) completed a home screen, and (3) completed an on-site diagnostic
      assessment. All procedures were culturally tailored to the presenting needs of
      families. RESULTS: Predisposing characteristics, enabling resources and need
      characteristics emerged as significant predictors of child mental health service
      use, with some variations. Child age, ethnicity, referral source, and enabling
      resources predicted completion of a home screen. Proximity to services predicted
      completion of the on-site diagnostic assessment. CONCLUSION: Knowledge of factors
      that predict engagement in child mental health services can help identify avenues
      to promote service utilization, especially among ethnic minority children and
      families. Our culturally tailored approach to serving families appears to be
      promising in bridging the cross-ethnic services gap and therefore has
      implications for practice.

PMID- 24683302
TI  - Inter-rater Reliability of the Anxiety Disorders Interview Schedule for DSM-IV in
      High-Functioning Youth with Autism Spectrum Disorder.
AB  - The present study examined inter-rater agreement on the Anxiety Disorder
      Interview Schedule DSM-IV Child and Parent Interview (ADIS-IV-C/P) in high
      functioning youth with autism spectrum disorder and if age and ASD diagnosis
      moderated agreement. Diagnoses established for 70 7 to 16-year-old youth with ASD
      during a live administration of the ADIS-IV-C/P were compared to diagnoses
      identified by a second rater after listening to audiotaped recordings of the
      interviews. Clinician-to-clinician agreement on individual parent and child
      reports was excellent (k=1.00). Inter-rater agreement on principal diagnoses
      (k=0.91), individual anxiety diagnoses (k=0.85-0.97), and other comorbid
      diagnoses (i.e., major depressive disorder, dysthymia, oppositional defiant
      disorder) (k=0.89-1.00) were excellent; agreement did not differ as a function of
      ASD diagnosis or age. Results suggest good to excellent inter-rater agreement for
      disorders assessed by the ADIS-IV-C/P.

PMID- 24683303
TI  - Massively parallel nonparametric regression, with an application to developmental
      brain mapping.
AB  - We propose a penalized spline approach to performing large numbers of parallel
      non-parametric analyses of either of two types: restricted likelihood ratio tests
      of a parametric regression model versus a general smooth alternative, and
      nonparametric regression. Compared with naively performing each analysis in turn,
      our techniques reduce computation time dramatically. Viewing the large collection
      of scatterplot smooths produced by our methods as functional data, we develop a
      clustering approach to summarize and visualize these results. Our approach is
      applicable to ultra-high-dimensional data, particularly data acquired by
      neuroimaging; we illustrate it with an analysis of developmental trajectories of
      functional connectivity at each of approximately 70000 brain locations.
      Supplementary materials, including an appendix and an R package, are available
      online.

PMID- 24683304
TI  - Parental Knowledge and Substance Use among African American Adolescents:
      Influence of Gender and Grade Level.
AB  - Parental knowledge is defined as parental awareness and information about a
      child's activities, whereabouts, and associations that is obtained through
      parental monitoring, parental solicitation, or self-disclosure. Increased
      parental knowledge is generally associated with lower adolescent substance use;
      however, the influence of various contextual factors, such as adolescent gender
      and grade level is not well understood, particularly for different racial or
      ethnic groups. In the present study, we used Hierarchical Generalized Linear
      Modeling (HGLM) analyses to examine the longitudinal relationship of parental
      knowledge to adolescent substance use in the context of adolescent gender and
      grade level among 207 urban African American adolescents in grades 6-11. Results
      indicated that increased parental knowledge is associated with a concurrent lower
      likelihood of substance use across all types of substances examined (alcohol,
      tobacco, marijuana, other drug use, and any drug use), but it did not predict
      changes in substance use one year later for the entire sample. However, analyses
      by gender and grade level showed that for boys and middle school youth, parental
      knowledge was a protective factor for increases in substance use across one year.
      Findings are discussed in terms of their implications for prevention and health
      promotion interventions for adolescent substance use among African American
      youth.

PMID- 24683305
TI  - An In Silico Approach for Characterization of an Aminoglycoside Antibiotic
      Resistant Methyltransferase Protein from Pyrococcus furiosus (DSM 3638).
AB  - Pyrococcus furiosus is a hyperthermophilic archaea. A hypothetical protein of
      this archaea, PF0847, was selected for computational analysis. Basic local
      alignment search tool and multiple sequence alignment (MSA) tool were employed to
      search for related proteins. Both the secondary and tertiary structure prediction
      were obtained for further analysis. Three-dimensional model was assessed by
      PROCHECK and QMEAN6 programs. To get insights about the physical and functional
      associations of the protein, STRING network analysis was performed. Binding of
      the SAM (S-adenosyl-l-methionine) ligand with our protein, fetched from an
      antibiotic-related methyltransferase (PDB code: 3P2K: D), showed high docking
      energy and suggested the function of the protein as methyltransferase. Finally,
      we tried to look for a specific function of the proposed methyltransferase, and
      binding of the geneticin bound to the eubacterial 16S rRNA A-site (PDB code:
      1MWL) in the active site of the PF0847 gave us the indication to predict the
      protein responsible for aminoglycoside antibiotic resistance. 

PMID- 24683307
TI  - A rare case of double-chambered right ventricle associated with ventricular
      septal defect and congenital absence of the pulmonary valve.
AB  - Double-chambered right ventricle (DCRV) is a rare congenital heart disorder
      involving 2 different right ventricle (RV) pressure compartments that is often
      associated with ventricular septal defect (VSD). Usually, the obstruction is
      caused by an anomalous muscle bundle crossing the RV from the interventricular
      septum to the RV free wall. We are reporting a case of double-chambered right
      ventricle associated with ventricular septal defect and congenital absence of the
      pulmonary valve, a rare form of congenital infundibular pulmonary stenosis. In
      addition to ventricular septal defect, our patient had congenital absence of the
      pulmonary valve, which is very unusual and has never been reported to our
      knowledge. 

PMID- 24683306
TI  - Genetics of bipolar disorder.
AB  - Bipolar disorder is a common, complex genetic disorder, but the mode of
      transmission remains to be discovered. Many researchers assume that common
      genomic variants carry some risk for manifesting the disease. The research
      community has celebrated the first genome-wide significant associations between
      common single nucleotide polymorphisms (SNPs) and bipolar disorder. Currently,
      attempts are under way to translate these findings into clinical practice,
      genetic counseling, and predictive testing. However, some experts remain
      cautious. After all, common variants explain only a very small percentage of the
      genetic risk, and functional consequences of the discovered SNPs are
      inconclusive. Furthermore, the associated SNPs are not disease specific, and the
      majority of individuals with a "risk" allele are healthy. On the other hand,
      population-based genome-wide studies in psychiatric disorders have rediscovered
      rare structural variants and mutations in genes, which were previously known to
      cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian
      syndromes, psychiatric symptoms are prevalent. Although these conditions do not
      fit the classic description of any specific psychiatric disorder, they often show
      nonspecific psychiatric symptoms that cross diagnostic boundaries, including
      intellectual disability, behavioral abnormalities, mood disorders, anxiety
      disorders, attention deficit, impulse control deficit, and psychosis. Although
      testing for chromosomal disorders and monogenic Mendelian disorders is well
      established, testing for common variants is still controversial. The standard
      concept of genetic testing includes at least three broad criteria that need to be
      fulfilled before new genetic tests should be introduced: analytical validity,
      clinical validity, and clinical utility. These criteria are currently not
      fulfilled for common genomic variants in psychiatric disorders. Further work is
      clearly needed before genetic testing for common variants in psychiatric
      disorders should be established. 

PMID- 24683308
TI  - Urban adolescents readily comply with a complicated asthma research protocol.
AB  - PURPOSE: Adolescents are often cited as having poor rates of compliance with
      medical regimens and research protocols. We quantified compliance in a cohort of
      urban adolescents participating in a complex research protocol in which measures
      were obtained without direct supervision by research personnel. METHODS: A total
      of 54 early adolescents ages 10-13 were asked to wear a vest containing a
      personal air pollutant exposure monitor for two 24-hour periods and to perform
      daily peak expiratory flow (PEF) for six consecutive days. Compliance with
      wearing the vest was measured by comparing accelerometer data from a device
      within the vest to one worn continuously on the child's wrist. Daily PEF data
      were recorded using an electronic meter. RESULTS: A priori definition of
      compliance was met by 85% of the adolescents by wearing the exposure monitoring
      vest and 72% by performing PEF. CONCLUSIONS: These findings suggest that early
      adolescents can be compliant with complex research protocols that are needed to
      help bridge gaps in pediatric asthma research.

PMID- 24683309
TI  - "Tell me I'm sexy...and otherwise valuable:" Body Valuation and Relationship
      Satisfaction.
AB  - Although extant research demonstrates that body valuation by strangers has
      negative implications for women, Studies 1 and 2 demonstrate that body valuation
      by a committed male partner is positively associated with women's relationship
      satisfaction when that partner also values them for their non-physical qualities,
      but negatively associated with women's relationship satisfaction when that
      partner is not committed or does not value them for their non-physical qualities.
      Study 3 demonstrates that body valuation by a committed female partner is
      negatively associated with men's relationship satisfaction when that partner does
      not also value them for their non-physical qualities but unassociated with men's
      satisfaction otherwise. These findings join others demonstrating that fully
      understanding the implications of interpersonal processes requires considering
      the interpersonal context. (120 words).

PMID- 24683310
TI  - Epidemiology, treatment patterns, and outcomes of metastatic soft tissue sarcoma
      in a community-based oncology network.
AB  - Purpose. To assess epidemiology, treatment patterns, and outcomes of metastatic
      soft tissue sarcoma (mSTS) patients in USA community oncology practices. Methods.
      This retrospective, descriptive study used US Oncology's iKnowMed electronic
      health records database. Adults (>=18 years) with mSTS and at least two visits
      between July 2007 and June 2010 were included. Key outcomes were practice
      patterns, overall survival (OS), and progression-free survival (PFS). Results.
      363 mSTS patients (174 treated and 189 untreated) met the prespecified
      exclusion/inclusion criteria. The most common subtypes were leiomyosarcoma (n =
      104; 29%), liposarcoma (n = 40; 11%), and synovial sarcoma (n = 12; 3%); the
      remainder (n = 207; 57%) comprised 27 histologic subtypes. Treated patients were
      younger and had lower ECOG scores; 75% and 25% received first-line combination or
      monotherapy, respectively. Median OS of treated and untreated patients was 22 and
      17 months, respectively, and 29 months in patients with the three most common
      subtypes. Before controlling for effects of covariates, younger age and lower
      ECOG scores were associated with better OS and PFS. Conclusion. This study
      provides insights into mSTS epidemiology, treatment patterns, and outcomes in a
      large community-based oncology network. These results warrant further studies
      with larger cohorts. 

PMID- 24683311
TI  - Cohen's Conservatism and Human Enhancement.
AB  - In an intriguing essay, G. A. Cohen has defended a conservative bias in favour of
      existing value. In this paper, we consider whether Cohen's conservatism raises a
      new challenge to the use of human enhancement technologies. We develop some of
      Cohen's suggestive remarks into a new line of argument against human enhancement
      that, we believe, is in several ways superior to existing objections. However, we
      shall argue that on closer inspection, Cohen's conservatism fails to offer
      grounds for a strong sweeping objection to enhancement, and may even offer
      positive support for forms of enhancement that preserve valuable features of
      human beings. Nevertheless, we concede that Cohen's arguments may suggest some
      plausible and important constraints on the modality of legitimate and desirable
      enhancements.

PMID- 24683312
TI  - Transitioning into the Community: Outcomes of a Pilot Housing Program for
      Forensic Patients.
AB  - The Transitional Rehabilitation Housing Pilot (TRHP) was designed to transition
      hospitalized forensic patients to the community. Twenty clients and their
      clinicians in two Ontario cities completed measures on functioning, substance
      use, recovery, social support, and quality of life at admission to the program
      and then every 6 months until 18 months post-admission. Clients also responded to
      open-ended questions on the impact of the program and living in the community on
      their recovery. Three (15%) clients re-offended. Eleven clients (55%) experienced
      rehospitalization; however, brief rehospitalization was seen as part of the
      recovery process. Level of community functioning was stable across time and 35%
      of clients had a decrease in the restrictiveness of their disposition order.
      Clients described numerous characteristics of community living that contributed
      to improvements in functioning, such as integration into the community, social
      contact, and newfound independence. Some aspects of TRHP that encouraged recovery
      included developing new skills and knowledge, staff support, and the programming
      that engaged clients in treatment and recovery-oriented activities. Findings
      suggest that forensic patients can transition successfully into the community
      with appropriate support and housing.

PMID- 24683313
TI  - Neonatal Intensive-Care Unit Graduates Show Persistent Difficulties in an Intra
      Dimensional Shift Card Sort.
AB  - Neonatal intensive-care unit (NICU) graduates, a group at risk for attention
      problems and ADHD, performed an intra-dimensional shift card sort at 34, 42, 51,
      and 60 months to assess executive function and to examine effects of individual
      risk factors. In the 'silly' game, children sorted cards (airplanes and dogs) so
      they were not the same as targets. In the 'same' game they did the opposite.
      Performance on the 'silly' game was poor, especially when it was presented first.
      Success in following 'silly' game rules improved with age, and was significantly
      linked to maternal education and birth weight for gestational age, a measure of
      intrauterine stress. Degree of CNS injury differentiated children who completed
      the task from children who did not, and also affected the need to repeat
      instructions in the 'same' game. These results confirm an increased likelihood of
      impairments in executive function during preschool years in NICU graduates.

PMID- 24683314
TI  - Assessing Bisexual Stigma and Mental Health Status: A Brief Report.
AB  - Bisexual women often report higher rates of depression and mental health problems
      than their heterosexual and lesbian counterparts. These disparities likely occur,
      in part, as a result of the unique stigma that bisexual women face and
      experience. Such stigma can in turn operate as a stressor, thereby contributing
      to poor mental health status. The current pilot study tested a new measure of
      bisexual stigma and its association with mental health. Results suggest a
      moderate positive correlation between the two, and point to areas for future
      consideration when measuring bisexual stigma.

PMID- 24683315
TI  - Children's Coping in the Context of Disasters and Terrorism.
AB  - Disasters and terrorism present significant and often overwhelming challenges for
      children and families worldwide. Individual, family, and social factors influence
      disaster reactions and the diverse ways in which children cope. This article
      links conceptualizations of stress and coping to empirical knowledge of
      children's disaster reactions, identifies limitations in our current
      understanding, and suggests areas for future study of disaster coping. Coping
      strategies, developmental trajectories influencing coping, and the interplay
      between parent and child coping represent critical areas for advancing the field
      and for informing programs and services that benefit children's preparedness and
      foster resilience in the face of mass trauma.

PMID- 24683316
TI  - Approximation of bivariate functions via smooth extensions.
AB  - For a smooth bivariate function defined on a general domain with arbitrary shape,
      it is difficult to do Fourier approximation or wavelet approximation. In order to
      solve these problems, in this paper, we give an extension of the bivariate
      function on a general domain with arbitrary shape to a smooth, periodic function
      in the whole space or to a smooth, compactly supported function in the whole
      space. These smooth extensions have simple and clear representations which are
      determined by this bivariate function and some polynomials. After that, we expand
      the smooth, periodic function into a Fourier series or a periodic wavelet series
      or we expand the smooth, compactly supported function into a wavelet series.
      Since our extensions are smooth, the obtained Fourier coefficients or wavelet
      coefficients decay very fast. Since our extension tools are polynomials, the
      moment theorem shows that a lot of wavelet coefficients vanish. From this, with
      the help of well-known approximation theorems, using our extension methods, the
      Fourier approximation and the wavelet approximation of the bivariate function on
      the general domain with small error are obtained. 

PMID- 24683317
TI  - Efficient iris recognition based on optimal subfeature selection and weighted
      subregion fusion.
AB  - In this paper, we propose three discriminative feature selection strategies and
      weighted subregion matching method to improve the performance of iris recognition
      system. Firstly, we introduce the process of feature extraction and
      representation based on scale invariant feature transformation (SIFT) in detail.
      Secondly, three strategies are described, which are orientation probability
      distribution function (OPDF) based strategy to delete some redundant feature
      keypoints, magnitude probability distribution function (MPDF) based strategy to
      reduce dimensionality of feature element, and compounded strategy combined OPDF
      and MPDF to further select optimal subfeature. Thirdly, to make matching more
      effective, this paper proposes a novel matching method based on weighted sub
      region matching fusion. Particle swarm optimization is utilized to accelerate
      achieve different sub-region's weights and then weighted different subregions'
      matching scores to generate the final decision. The experimental results, on
      three public and renowned iris databases (CASIA-V3 Interval, Lamp, and MMU-V1),
      demonstrate that our proposed methods outperform some of the existing methods in
      terms of correct recognition rate, equal error rate, and computation complexity.

PMID- 24683318
TI  - A simple SQP algorithm for constrained finite minimax problems.
AB  - A simple sequential quadratic programming method is proposed to solve the
      constrained minimax problem. At each iteration, through introducing an auxiliary
      variable, the descent direction is given by solving only one quadratic
      programming. By solving a corresponding quadratic programming, a high-order
      revised direction is obtained, which can avoid the Maratos effect. Furthermore,
      under some mild conditions, the global and superlinear convergence of the
      algorithm is achieved. Finally, some numerical results reported show that the
      algorithm in this paper is successful. 

PMID- 24683319
TI  - Stability calculation method of slope reinforced by prestressed anchor in process
      of excavation.
AB  - This paper takes the effect of supporting structure and anchor on the slope
      stability of the excavation process into consideration; the stability calculation
      model is presented for the slope reinforced by prestressed anchor and grillage
      beam, and the dynamic search model of the critical slip surface also is put
      forward. The calculation model of the optimal stability solution of each anchor
      tension of the whole process is also given out, through which the real-time
      analysis and checking of slope stability in the process of excavation can be
      realized. The calculation examples indicate that the slope stability is changed
      with the dynamic change of the design parameters of anchor and grillage beam. So
      it is relatively more accurate and reasonable by using dynamic search model to
      determine the critical slip surface of the slope reinforced by prestressed anchor
      and grillage beam. Through the relationships of each anchor layout and the slope
      height of various stages of excavation, and the optimal stability solution of
      prestressed bolt tension design value in various excavation stages can be
      obtained. The arrangement of its prestressed anchor force reflects that the
      layout of the lower part of bolt and the calculation of slope reinforcement is in
      line with the actual. These indicate that the method is reasonable and practical.

PMID- 24683320
TI  - Exploration on bioflocculation of Nannochloropsis oculata using response surface
      methodology for biodiesel production.
AB  - Harvesting of algal biomass in biodiesel production involves high energy input
      and cost incurred process. In order to overcome these problems, bioflocculation
      process was employed and the efficiency of this process was further improved by
      the addition of a cationic inducer. In this work marine Bacillus subtilis was
      used for bioflocculation of Nannochloropsis oculata and ZnCl2 as cationic
      inducer. This study worked under the principle of divalent cationic bridging
      (DCB) theory. Under temperature stress and high pH, the bacterium produced
      exopolysaccharide that bound with microalga Nannochloropsis oculata and
      flocculated them. A maximum efficiency of 95.43% was observed with the optimised
      RSM parameters-temperature 30.78 degrees C, pH 10.8, flocculation time 6.7 h,
      bioflocculant size 0.38 mL, and cationic inducer concentration 0.035 mM. The
      present investigation focused on the cost effective harvesting of microalga on a
      larger scale for biodiesel production than using toxic, ecofriendly chemical
      flocculants.

PMID- 24683321
TI  - Adaptive super-twisting observer for estimation of random road excitation profile
      in automotive suspension systems.
AB  - The estimation of road excitation profile is important for evaluation of vehicle
      stability and vehicle suspension performance for autonomous vehicle control
      systems. In this work, the nonlinear dynamics of the active automotive system
      that is excited by the unknown road excitation profile are considered for
      modeling. To address the issue of estimation of road profile, we develop an
      adaptive supertwisting observer for state and unknown road profile estimation.
      Under Lipschitz conditions for the nonlinear functions, the convergence of the
      estimation error is proven. Simulation results with Ford Fiesta MK2 demonstrate
      the effectiveness of the proposed observer for state and unknown input estimation
      for nonlinear active suspension system. 

PMID- 24683322
TI  - Thermodynamics of cadmium sorption on different soils of West Bengal, India.
AB  - A sorption study was conducted on different soils collected from five
      agroecological zones of West Bengal, India, to understand the soil environmental
      behavior and fate of cadmium. For this purpose batch adsorption experiments were
      carried out at the native soil pH and at three different temperatures (25 degrees
      C, 35 degrees C, and 45 degrees C). The adsorption data fitted by a linear least
      squares technique to the different sorption isotherms. Most data obtained give
      the good fit to both Freundlich and modified Langmuir isotherms, but they are not
      consistent with the linear Langmuir adsorption model. Thermodynamic parameters,
      namely, thermodynamics equilibrium constant at a particular temperature T (K T
      (0)), Gibbs free energy at a particular temperature T (DeltaG T (0)), and change
      of enthalpy (DeltaH (0)) and change of entropy at temperature T (DeltaS T (0)),
      were also determined by applying sorption value and concentrations of Cd in
      equilibrium solution within the temperature range. The thermodynamic parameters
      revealed that Cd sorption increases as the values of K T (0), DeltaG T (0),
      DeltaH (0), and DeltaS T (0) were increased on reaction temperatures. The
      spontaneous sorption reaction can be concluded due to high values of DeltaG T
      (0). The positive values of DeltaH (0) indicated that the Cd sorption is an
      endothermic one. Under these present conditions, the soil and its components
      possibly supply a number of sites having different adsorption energies for
      cadmium sorption.

PMID- 24683324
TI  - The influence of doping with transition metal ions on the structure and magnetic
      properties of zinc oxide thin films.
AB  - Zn1-x Ni x O (x = 0.03 / 0.10) and Zn1-x Fe x O (x = 0.03 / 0.15) thin films were
      synthesized by sol-gel method. The structure and the surface morphology of zinc
      oxide thin films doped with transition metal (TM) ions have been investigated by
      X-ray diffraction (XRD) and atomic force microscopy (AFM). The magnetic studies
      were done using vibrating sample magnetometer (VSM) at room temperature.
      Experimental results revealed that the substitution of Ni ions in ZnO wurtzite
      lattice for the contents x = 0.03 / 0.10 (Ni(2+)) leads to weak ferromagnetism of
      thin films. For Zn1-x Fe x O with x = 0.03 / 0.05, the Fe(3+) ions are magnetic
      coupling by superexchange interaction via oxygen ions in wurtzite structure. For
      x = 0.10 / 0.15 (Fe(3+)) one can observe the increasing of secondary phase of
      ZnFe2O4 spinel. The Zn0.9Fe0.1O film shows a superparamagnetic behavior due to
      small crystallite sizes and the net spin magnetic moments arisen from the
      interaction between the iron ions through an oxygen ion in the spinel structure.

PMID- 24683323
TI  - A novel role of globular adiponectin in treatment with HFD/STZ induced T2DM
      combined with NAFLD rats.
AB  - AIMS: To evaluate the effects of globular adiponectin (gAd) on treatment of type
      2 diabetic rats combined with NAFLD. MATERIALS AND METHODS: Twenty-one male
      wistar rats were fed with normal diet (7 rats) or high fat diet (HFD) (14 rats)
      for 4 weeks, and then HFD-fed rats were injected with streptozotocin (STZ) to
      induce type 2 diabetes mellitus (T2DM). Half of T2DM rats were randomly injected
      with gAd intraperitoneally for 7 days. The expressions of adiponectin receptors
      (adipoR1/R2) in liver and skeletal muscle tissues were detected through western
      blotting or RT-qPCR, respectively. RESULTS: Globular adiponectin alleviated the
      hepatic steatosis and increased insulin secretion. In liver, both the protein and
      mRNA expressions of adipoR2 in T2DM group decreased (P < 0.05, resp.) in contrast
      to NC group and increased (P < 0.05 and P < 0.001, resp.) after gAd treatment.
      But the protein and mRNA expressions of adipoR1 increased (P < 0.05, resp.) in
      T2DM group and no change was found in the gAd-treated group. In skeletal muscle,
      the protein and mRNA expressions of adipoR1 and adipoR2 were upregulated in T2DM
      group and were downregulated after gAd treatment. CONCLUSIONS: Globular
      adiponectin could ameliorate the hepatic steatosis and vary the expressions of
      adiponectin receptors in liver and skeletal muscle by stimulating insulin
      secretion.

PMID- 24683325
TI  - Generalized uniqueness theorem for ordinary differential equations in Banach
      spaces.
AB  - We consider nonlinear ordinary differential equations in Banach spaces.
      Uniqueness criterion for the Cauchy problem is given when any of the standard
      dissipative-type conditions does apply. A similar scalar result has been studied
      by Majorana (1991). Useful examples of reflexive Banach spaces whose positive
      cones have empty interior has been given as well. 

PMID- 24683326
TI  - Development of simple designs of multitip probe diagnostic systems for RF plasma
      characterization.
AB  - Multitip probes are very useful diagnostics for analyzing and controlling the
      physical phenomena occurring in low temperature discharge plasmas. However, DC
      biased probes often fail to perform well in processing plasmas. The objective of
      the work was to deduce simple designs of DC biased multitip probes for parametric
      study of radio frequency plasmas. For this purpose, symmetric double probe,
      asymmetric double probe, and symmetric triple probe diagnostic systems and their
      driving circuits were designed and tested in an inductively coupled plasma (ICP)
      generated by a 13.56 MHz radio frequency (RF) source. Using I-V characteristics
      of these probes, electron temperature, electron number density, and ion
      saturation current was measured as a function of input power and filling gas
      pressure. An increasing trend was noticed in electron temperature and electron
      number density for increasing input RF power whilst a decreasing trend was
      evident in these parameters when measured against filling gas pressure. In
      addition, the electron energy probability function (EEPF) was also studied by
      using an asymmetric double probe. These studies confirmed the non-Maxwellian
      nature of the EEPF and the presence of two groups of the energetic electrons at
      low filling gas pressures.

PMID- 24683327
TI  - Effective multifocus image fusion based on HVS and BP neural network.
AB  - The aim of multifocus image fusion is to fuse the images taken from the same
      scene with different focuses to obtain a resultant image with all objects in
      focus. In this paper, a novel multifocus image fusion method based on human
      visual system (HVS) and back propagation (BP) neural network is presented. Three
      features which reflect the clarity of a pixel are firstly extracted and used to
      train a BP neural network to determine which pixel is clearer. The clearer pixels
      are then used to construct the initial fused image. Thirdly, the focused regions
      are detected by measuring the similarity between the source images and the
      initial fused image followed by morphological opening and closing operations.
      Finally, the final fused image is obtained by a fusion rule for those focused
      regions. Experimental results show that the proposed method can provide better
      performance and outperform several existing popular fusion methods in terms of
      both objective and subjective evaluations. 

PMID- 24683328
TI  - Alternative paradigm of selective vagus nerve stimulation tested on an isolated
      porcine vagus nerve.
AB  - Alternative paradigm for spatial and fibre-type selective vagus nerve stimulation
      (VNS) was developed using realistic structural topography and tested in an
      isolated segment of a porcine cervical left vagus nerve (LVN). A spiral cuff
      (cuff) containing a matrix of ninety-nine electrodes was developed for selective
      VNS. A quasitrapezoidal stimulating pulse (stimulus) was applied to the LVN via
      an appointed group of three electrodes (triplet). The triplet and stimulus were
      configured to predominantly stimulate the B-fibres, minimizing stimulation of the
      A-fibres and by-passing the stimulation of the C-fibres. To assess which fibres
      made the most probable contribution to the neural response (NR) during selective
      VNS, the distribution of conduction velocity (CV) within the LVN was considered.
      Experimental testing of the paradigm showed the existence of certain parameters
      and waveforms of the stimulus, for which the contribution of the A-fibres to the
      NR was slightly reduced and that of the B-fibres was slightly enlarged. The cuff
      provided satisfactory fascicle discrimination in selective VNS as well as
      satisfactory fascicle discrimination during NR recording. However, in the present
      stage of development, fibre-type VNS remained rather limited. 

PMID- 24683329
TI  - Heterogeneous differential evolution for numerical optimization.
AB  - Differential evolution (DE) is a population-based stochastic search algorithm
      which has shown a good performance in solving many benchmarks and real-world
      optimization problems. Individuals in the standard DE, and most of its
      modifications, exhibit the same search characteristics because of the use of the
      same DE scheme. This paper proposes a simple and effective heterogeneous DE (HDE)
      to balance exploration and exploitation. In HDE, individuals are allowed to
      follow different search behaviors randomly selected from a DE scheme pool.
      Experiments are conducted on a comprehensive set of benchmark functions,
      including classical problems and shifted large-scale problems. The results show
      that heterogeneous DE achieves promising performance on a majority of the test
      problems. 

PMID- 24683332
TI  - An energy-economy-environment model for simulating the impacts of socioeconomic
      development on energy and environment.
AB  - Many rapidly developing regions have begun to draw the attention of the world.
      Meanwhile, the energy and environmental issues associated with rapid economic
      growth have aroused widespread critical concern. Therefore, studying energy,
      economic, and environmental systems is of great importance. This study
      establishes a system dynamic model that covers multiple aspects of those systems,
      such as energy, economy, population, water pollution, air pollution, solid waste,
      and technology. The model designed here attempts to determine the impacts of
      socioeconomic development on the energy and environment of Tongzhou District in
      three scenarios: under current, planning, and sustainable conditions. The results
      reveal that energy shortages and water pollutions are very serious and are the
      key issues constraining future social and economic development. Solid waste
      emissions increase with population growth. The prediction results provide
      valuable insights into social advancement. 

PMID- 24683333
TI  - Simulation and modeling efforts to support decision making in healthcare supply
      chain management.
AB  - Recently, most healthcare organizations focus their attention on reducing the
      cost of their supply chain management (SCM) by improving the decision making
      pertaining processes' efficiencies. The availability of products through
      healthcare SCM is often a matter of life or death to the patient; therefore,
      trial and error approaches are not an option in this environment. Simulation and
      modeling (SM) has been presented as an alternative approach for supply chain
      managers in healthcare organizations to test solutions and to support decision
      making processes associated with various SCM problems. This paper presents and
      analyzes past SM efforts to support decision making in healthcare SCM and
      identifies the key challenges associated with healthcare SCM modeling. We also
      present and discuss emerging technologies to meet these challenges. 

PMID- 24683330
TI  - Anesthetic techniques and cancer recurrence after surgery.
AB  - Many of the most common anesthetics are used in surgical oncology, yet effects on
      cancer cells are still not known. Anesthesia technique could differentially
      affect cancer recurrence in oncologic patients undergoing surgery, due to
      immunosuppression, stimulation of angiogenesis, and dissemination of residual
      cancer cells. Data support the use of intravenous anesthetics, such as propofol
      anesthesia, thanks to antitumoral protective effects inhibiting cyclooxygenase 2
      and prostaglandins E2 in cancer cells, and stimulation of immunity response; a
      restriction in the use of volatile anesthetics; restriction in the use of opioids
      as they suppress humoral and cellular immunity, and their chronic use favors
      angiogenesis and development of metastases; use of locoregional anesthesia
      compared with general anesthesia, as locoregional appears to reduce cancer
      recurrence after surgery. However, these findings must be interpreted cautiously
      as there is no evidence that simple changes in the practice of anesthesia can
      have a positive impact on postsurgical survival of cancer patients. 

PMID- 24683331
TI  - Seroprevalence of Toxoplasma gondii infection in sows in Hunan province, China.
AB  - Toxoplasma gondii infections are prevalent in animals and humans worldwide.
      Although the prevalence of T. gondii has been reported in many animals in China,
      little is known of T. gondii infection in sows. Antibodies to T. gondii in sows
      in Hunan province, subtropical China, were examined using indirect
      hemagglutination test (IHAT). Overall, 31.3% (373/1191) of the examined sows were
      seropositive for T. gondii. Among 11 representative regions of Hunan province,
      the seroprevalence ranged from 14.8% to 45.1%. In addition, the T. gondii
      seroprevalence was higher in summer (37.4%) and autumn (34.9%) than in spring
      (24.6%) and winter (23.9%). Regarding different antibody titers, the
      seroprevalence ranged from 1.8% (titer >= 1: 1024) to 17.4% (titer = 1:64). The
      findings of the present investigation revealed the high seroprevalence of T.
      gondii in sows in Hunan province, China, which poses a potential risk for T.
      gondii infection in humans and animals in this province. Therefore, effective
      measures should be taken to prevent and control toxoplasmosis of pigs in this
      province. This is the first report of the comprehensive survey of T. gondii
      seroprevalence in sows in Hunan Province, subtropical China.

PMID- 24683334
TI  - Multiobjective robust design of the double wishbone suspension system based on
      particle swarm optimization.
AB  - The performance of the suspension system is one of the most important factors in
      the vehicle design. For the double wishbone suspension system, the conventional
      deterministic optimization does not consider any deviations of design parameters,
      so design sensitivity analysis and robust optimization design are proposed. In
      this study, the design parameters of the robust optimization are the positions of
      the key points, and the random factors are the uncertainties in manufacturing. A
      simplified model of the double wishbone suspension is established by software
      ADAMS. The sensitivity analysis is utilized to determine main design variables.
      Then, the simulation experiment is arranged and the Latin hypercube design is
      adopted to find the initial points. The Kriging model is employed for fitting the
      mean and variance of the quality characteristics according to the simulation
      results. Further, a particle swarm optimization method based on simple PSO is
      applied and the tradeoff between the mean and deviation of performance is made to
      solve the robust optimization problem of the double wishbone suspension system. 

PMID- 24683335
TI  - Analysis of paralleling limited capacity voltage sources by projective geometry
      method.
AB  - The droop current-sharing method for voltage sources of a limited capacity is
      considered. Influence of equalizing resistors and load resistor is investigated
      on uniform distribution of relative values of currents when the actual loading
      corresponds to the capacity of a concrete source. Novel concepts for quantitative
      representation of operating regimes of sources are entered with use of projective
      geometry method. 

PMID- 24683337
TI  - A note on the Drazin indices of square matrices.
AB  - For a square matrix A, the smallest nonnegative integer k such that rank (A(k))
      =rank (A(k+1)) is called the Drazin index of A. In this paper, we give some
      results on the Drazin indices of sum and product of square matrices.

PMID- 24683336
TI  - Allocation of secondary metabolites, photosynthetic capacity, and antioxidant
      activity of Kacip Fatimah (Labisia pumila Benth) in response to CO2 and light
      intensity.
AB  - A split plot 3 by 4 experiment was designed to investigate and distinguish the
      relationships among production of secondary metabolites, soluble sugar,
      phenylalanine ammonia lyase (PAL; EC 4.3.1.5) activity, leaf gas exchange,
      chlorophyll content, antioxidant activity (DPPH), and lipid peroxidation under
      three levels of CO2 (400, 800, and 1200 MU mol/mol) and four levels of light
      intensity (225, 500, 625, and 900 MU mol/m(2)/s) over 15 weeks in Labisia pumila.
      The production of plant secondary metabolites, sugar, chlorophyll content,
      antioxidant activity, and malondialdehyde content was influenced by the
      interactions between CO2 and irradiance. The highest accumulation of secondary
      metabolites, sugar, maliondialdehyde, and DPPH activity was observed under CO2 at
      1200 MU mol/mol + light intensity at 225 MU mol/m(2)/s. Meanwhile, at 400 MU
      mol/mol CO2 + 900 MU mol/m(2)/s light intensity the production of chlorophyll and
      maliondialdehyde content was the highest. As CO2 levels increased from 400 to
      1200 MU mol/mol the photosynthesis, stomatal conductance, f v /f m (maximum
      efficiency of photosystem II), and PAL activity were enhanced. The production of
      secondary metabolites displayed a significant negative relationship with
      maliondialdehyde indicating lowered oxidative stress under high CO2 and low
      irradiance improved the production of plant secondary metabolites that
      simultaneously enhanced the antioxidant activity (DPPH), thus improving the
      medicinal value of Labisia pumila under this condition.

PMID- 24683338
TI  - Strain sensor of carbon nanotubes in microscale: from model to metrology.
AB  - A strain sensor composed of carbon nanotubes with Raman spectroscopy can achieve
      measurement of the three in-plane strain components in microscale. Based on
      previous work on the mathematic model of carbon nanotube strain sensors, this
      paper presents a detailed study on the optimization, diversification, and
      standardization of a CNT strain sensor from the viewpoint of metrology. A new
      miniaccessory for polarization control is designed, and two different preparing
      methods for CNT films as sensing media are introduced to provide diversified
      choices for applications. Then, the standard procedure of creating CNT strain
      sensors is proposed. Application experiments confirmed the effectiveness of the
      above improvement, which is helpful in developing this method for convenient
      metrology. 

PMID- 24683339
TI  - Aerodynamic characteristics of the ventilated design for flapping wing micro air
      vehicle.
AB  - Inspired by superior flight performance of natural flight masters like birds and
      insects and based on the ventilating flaps that can be opened and closed by the
      changing air pressure around the wing, a new flapping wing type has been
      proposed. It is known that the net lift force generated by a solid wing in a
      flapping cycle is nearly zero. However, for the case of the ventilated wing,
      results for the net lift force are positive which is due to the effect created by
      the "ventilation" in reducing negative lift force during the upstroke. The
      presence of moving flaps can serve as the variable in which, through careful
      control of the areas, a correlation with the decrease in negative lift can be
      generated. The corresponding aerodynamic characteristics have been investigated
      numerically by using different flapping frequencies and forward flight speeds. 

PMID- 24683340
TI  - Comparative analyses of phase noise in 28 nm CMOS LC oscillator circuit
      topologies: Hartley, Colpitts, and common-source cross-coupled differential pair.
AB  - This paper reports comparative analyses of phase noise in Hartley, Colpitts, and
      common-source cross-coupled differential pair LC oscillator topologies in 28 nm
      CMOS technology. The impulse sensitivity function is used to carry out both
      qualitative and quantitative analyses of the phase noise exhibited by each
      circuit component in each circuit topology with oscillation frequency ranging
      from 1 to 100 GHz. The comparative analyses show the existence of four distinct
      frequency regions in which the three oscillator topologies rank unevenly in terms
      of best phase noise performance, due to the combined effects of device noise and
      circuit node sensitivity.

PMID- 24683341
TI  - Nano-ZnO catalyzed multicomponent one-pot synthesis of novel spiro(indoline
      pyranodioxine) derivatives.
AB  - A simple catalytic protocol for the synthesis of novel spiro[indoline
      pyranodioxine] derivatives has been developed using ZnO nanoparticle as an
      efficient, green, and reusable catalyst. The derivatives are obtained in moderate
      to excellent yield by one-pot three-component reaction of an isatin,
      malononitrile/ethylcyanoacetate, and 2,2-dimethyl-1,3-dioxane-4,6-dione in
      absolute ethanol under conventional heating and microwave irradiation. The
      catalyst was recovered by filtration from the reaction mixture and reused during
      five consecutive runs without any apparent loss of activity for the same
      reaction. The mild reaction conditions and recyclability of the catalyst make it
      environmentally benign synthetic procedure. 

PMID- 24683342
TI  - The optimal licensing contract in a differentiated Stackelberg model.
AB  - This paper extends the work of Wang (2002) by considering a differentiated
      Stackelberg model, when the leader firm is an inside innovator and licenses its
      new technology by three options, that is, fixed-fee licensing, royalty licensing,
      and two-part tariff licensing. The main contributions and conclusions of this
      paper are threefold. First of all, this paper derives a very different result
      from Wang (2002). We show that, with a nondrastic innovation, royalty licensing
      is always better than fixed-fee licensing for the innovator; with a drastic
      innovation, royalty licensing is superior to fixed-fee licensing for small values
      of substitution coefficient d; however when d becomes closer to 1, neither fee
      nor royalty licensing will occur. Secondly, this paper shows that the innovator
      is always better off in case of two-part tariff licensing than fixed-fee
      licensing no matter what the innovation size is. Thirdly, the innovator always
      prefers to license its nondrastic innovation by means of a two-part tariff
      instead of licensing by means of a royalty; however, with a drastic innovation,
      the optimal licensing strategy can be either a two-part tariff or a royalty,
      depending upon the differentiation of the goods. 

PMID- 24683343
TI  - Photoinitiated polymerization of cationic acrylamide in aqueous solution:
      synthesis, characterization, and sludge dewatering performance.
AB  - A copolymer of acrylamide (AM) with acryloyloxyethyl trimethyl ammonium chloride
      (DAC) as the cationic monomer was synthesized under the irradiation of high
      pressure mercury lamp with 2,2-azobis(2-amidinopropane) dihydrochloride (V-50) as
      the photoinitiator. The compositions of the photoinduced copolymer were
      characterized by Fourier transform infrared spectra (FTIR), ultraviolet spectra
      (UV), and scanning electron microscope (SEM). The effects of 6 important factors,
      that is, photo-initiators concentration, monomers concentration, CO(NH2)2 (urea)
      concentrations, pH value, mass ratio of AM to DAC, and irradiation time on the
      molecular weight and dissolving time, were investigated. The optimal reaction
      conditions were that the photo-initiators concentration was 0.3%, monomers
      concentration was 30 wt.%, irradiation time was 60 min, urea concentration was
      0.4%, pH value was 5.0, and mass ratio of AM to DAC was 6 : 4. Its flocculation
      properties were evaluated with activated sludge using jar test. The zeta
      potential of supernatant at different cationic monomer contents was
      simultaneously measured. The results demonstrated the superiority of the
      copolymer over the commercial polyacrylamide as a flocculant.

PMID- 24683344
TI  - Antimicrobial effect of Lippia sidoides and thymol on Enterococcus faecalis
      biofilm of the bacterium isolated from root canals.
AB  - The species Lippia sidoides Cham. (Verbenaceae) is utilized in popular medicine
      as a local antiseptic on the skin and mucosal tissues. Enterococcus faecalis is
      the bacterium isolated from root canals of teeth with persistent periapical
      lesions and has the ability to form biofilm, where it is responsible for the
      failure of endodontic treatments. Essential oil of L. sidoides (EOLS) and its
      major component, thymol, were evaluated for reducing the CFU in biofilms of E.
      faecalis in vitro. The essential oil was obtained by hydrodistillation and
      examined with respect to the chemical composition, by gas chromatography-mass
      spectrometry (GC-MS). The GC-MS analysis has led to the identification of thymol
      (84.9%) and p-cymene (5.33%). EOLS and thymol reduced CFU in biofilms of E.
      faecalis in vitro (time of maturation, 72 h), with an exposure time of 30 and 60
      min at concentrations of 2.5 and 10%. There was no statistical difference in
      effect between EOLS and thymol, demontrating that this phenolic monoterpene was
      the possible compound responsible for the antimicrobial activity of EOLS. This
      study provides a basis for the possible utilization of EOLS as an adjuvant in the
      treatment of root canals that show colonization by E. faecalis.

PMID- 24683345
TI  - Complete moment convergence and mean convergence for arrays of rowwise extended
      negatively dependent random variables.
AB  - The authors first present a Rosenthal inequality for sequence of extended
      negatively dependent (END) random variables. By means of the Rosenthal
      inequality, the authors obtain some complete moment convergence and mean
      convergence results for arrays of rowwise END random variables. The results in
      this paper extend and improve the corresponding theorems by Hu and Taylor (1997).

PMID- 24683346
TI  - EEMD-MUSIC-based analysis for natural frequencies identification of structures
      using artificial and natural excitations.
AB  - This paper presents a new EEMD-MUSIC- (ensemble empirical mode decomposition
      multiple signal classification-) based methodology to identify modal frequencies
      in structures ranging from free and ambient vibration signals produced by
      artificial and natural excitations and also considering several factors as
      nonstationary effects, close modal frequencies, and noisy environments, which are
      common situations where several techniques reported in literature fail. The EEMD
      and MUSIC methods are used to decompose the vibration signal into a set of IMFs
      (intrinsic mode functions) and to identify the natural frequencies of a
      structure, respectively. The effectiveness of the proposed methodology has been
      validated and tested with synthetic signals and under real operating conditions.
      The experiments are focused on extracting the natural frequencies of a truss-type
      scaled structure and of a bridge used for both highway traffic and pedestrians.
      Results show the proposed methodology as a suitable solution for natural
      frequencies identification of structures from free and ambient vibration signals.

PMID- 24683347
TI  - Detection of amitraz resistance in Rhipicephalus (Boophilus) microplus from SBS
      Nagar, Punjab, India.
AB  - The resistance status of Rhipicephalus (Boophilus) microplus collected from SBS
      Nagar, Punjab, was evaluated against amitraz by Adult Immersion Test (AIT). The
      regression graph of probit mortality of ticks plotted against log values of
      progressively increasing concentrations of amitraz revealed the slope of
      mortality (95% CI) as 2.36 +/- 0.61 (0.38 to 4.33). The LC50 (95% CI) and LC95
      (95% CI) values were recorded as 332.52 ppm (305.06-362.44) and 1646.93 ppm
      (1383.97-1959.84), respectively, and the resistance factor (RF) was 13.17 which
      indicated level II resistance status. The dose response curves for egg mass
      weight, reproductive index, and percentage inhibition of oviposition were also
      validated by AIT and the slopes (95% CI) were -7.17 +/- 2.41 (-14.85 to 0.50), 
      0.009 +/- 0.02 (-0.16 to -0.031), and 19.99 +/- 4.77 (4.81 to 35.17),
      respectively. The current study reports the development of resistance in R. (B.)
      microplus to amitraz from Punjab state and the data generated would be useful in
      formulation of effective control strategies against ticks of this region.

PMID- 24683348
TI  - The study of cooperative obstacle avoidance method for MWSN based on flocking
      control.
AB  - Compared with the space fixed feature of traditional wireless sensor network
      (WSN), mobile WSN has better robustness and adaptability in unknown environment,
      so that it is always applied in the research of target tracking. In order to
      reach the target, the nodes group should find a self-adaptive method to avoid the
      obstacles together in their moving directions. Previous methods, which were based
      on flocking control model, realized the strategy of obstacle avoidance by means
      of potential field. However, these may sometimes lead the nodes group to fall
      into a restricted area like a trap and never get out of it. Based on traditional
      flocking control model, this paper introduced a new cooperative obstacle
      avoidance model combined with improved SA obstacle avoidance algorithm. It
      defined the tangent line of the intersection of node's velocity line and the edge
      of obstacle as the steering direction. Furthermore, the cooperative obstacle
      avoidance model was also improved in avoiding complex obstacles. When nodes group
      encounters mobile obstacles, nodes will predict movement path based on the
      spatial location and velocity of obstacle. And when nodes group enters concave
      obstacles, nodes will temporarily ignore the gravity of the target and search
      path along the edge of the concave obstacles. Simulation results showed that
      cooperative obstacle avoidance model has significant improvement on average speed
      and time efficiency in avoiding obstacle compared with the traditional flocking
      control model. It is more suitable for obstacle avoidance in complex environment.

PMID- 24683349
TI  - Error analysis for RADAR neighbor matching localization in linear logarithmic
      strength varying Wi-Fi environment.
AB  - This paper studies the statistical errors for the fingerprint-based RADAR
      neighbor matching localization with the linearly calibrated reference points
      (RPs) in logarithmic received signal strength (RSS) varying Wi-Fi environment. To
      the best of our knowledge, little comprehensive analysis work has appeared on the
      error performance of neighbor matching localization with respect to the
      deployment of RPs. However, in order to achieve the efficient and reliable
      location-based services (LBSs) as well as the ubiquitous context-awareness in Wi
      Fi environment, much attention has to be paid to the highly accurate and cost
      efficient localization systems. To this end, the statistical errors by the widely
      used neighbor matching localization are significantly discussed in this paper to
      examine the inherent mathematical relations between the localization errors and
      the locations of RPs by using a basic linear logarithmic strength varying model.
      Furthermore, based on the mathematical demonstrations and some testing results,
      the closed-form solutions to the statistical errors by RADAR neighbor matching
      localization can be an effective tool to explore alternative deployment of
      fingerprint-based neighbor matching localization systems in the future. 

PMID- 24683350
TI  - Network efficient power control for wireless communication systems.
AB  - We introduce a two-loop power control that allows an efficient use of the overall
      power resources for commercial wireless networks based on cross-layer
      optimization. This approach maximizes the network's utility in the outer-loop as
      a function of the averaged signal to interference-plus-noise ratio (SINR) by
      considering adaptively the changes in the network characteristics. For this
      purpose, the concavity property of the utility function was verified with respect
      to the SINR, and an iterative search was proposed with guaranteed convergence. In
      addition, the outer-loop is in charge of selecting the detector that minimizes
      the overall power consumption (transmission and detection). Next the inner-loop
      implements a feedback power control in order to achieve the optimal SINR in the
      transmissions despite channel variations and roundtrip delays. In our proposal,
      the utility maximization process and detector selection and feedback power
      control are decoupled problems, and as a result, these strategies are implemented
      at two different time scales in the two-loop framework. Simulation results show
      that substantial utility gains may be achieved by improving the power management
      in the wireless network. 

PMID- 24683351
TI  - A new subcarrier allocation strategy for MIMO-OFDMA multicellular networks based
      on cooperative interference mitigation.
AB  - The goal of the study presented in this paper is to investigate the performance
      of a new subcarrier allocation strategy for Orthogonal Frequency Division
      Multiple Access (OFDMA) multicellular networks which employ Multiple Input
      Multiple Output (MIMO) architecture. For this reason, a hybrid system-link level
      simulator has been developed executing independent Monte Carlo (MC) simulations
      in parallel. Up to two tiers of cells around the central cell are taken into
      consideration and increased loading per cell. The derived results indicate that
      this strategy can provide up to 12% capacity gain for 16-QAM modulation and two
      tiers of cells around the central cell in a symmetric 2 * 2 MIMO configuration.
      This gain is derived when comparing the proposed strategy to the traditional
      approach of allocating subcarriers that maximize only the desired user's signal. 

PMID- 24683352
TI  - Componential profile and amylase inhibiting activity of phenolic compounds from
      Calendula officinalis L. leaves.
AB  - An ethanolic extract and its ethyl acetate-soluble fraction from leaves of
      Calendula officinalis L. (Asteraceae) were found to show an inhibitory effect on
      amylase. From the crude extract fractions, one new phenolic acid glucoside, 6'-O
      vanilloyl-beta-D-glucopyranose, was isolated, together with twenty-four known
      compounds including five phenolic acid glucosides, five phenylpropanoids, five
      coumarins, and nine flavonoids. Their structures were elucidated based on
      chemical and spectral data. The main components, isoquercitrin, isorhamnetin-3-O
      beta-D-glucopyranoside, 3,5-di-O-caffeoylquinic acid, and quercetin-3-O-(6''
      acetyl)-beta-D-glucopyranoside, exhibited potent inhibitory effects on amylase.

PMID- 24683353
TI  - A novel approach for detail-enhanced exposure fusion using guided filter.
AB  - In this paper we propose a novel detail-enhancing exposure fusion approach using
      nonlinear translation-variant filter (NTF). With the captured Standard Dynamic
      Range (SDR) images under different exposure settings, first the fine details are
      extracted based on guided filter. Next, the base layers (i.e., images obtained
      from NTF) across all input images are fused using multiresolution pyramid.
      Exposure, contrast, and saturation measures are considered to generate a mask
      that guides the fusion process of the base layers. Finally, the fused base layer
      is combined with the extracted fine details to obtain detail-enhanced fused
      image. The goal is to preserve details in both very dark and extremely bright
      regions without High Dynamic Range Image (HDRI) representation and tone mapping
      step. Moreover, we have demonstrated that the proposed method is also suitable
      for the multifocus image fusion without introducing artifacts. 

PMID- 24683354
TI  - Antioxidant activity and phenolic content of microwave-assisted Solanum melongena
      extracts.
AB  - Eggplant fruit is a very rich source of polyphenol compounds endowed with
      antioxidant properties. The aim of this study was to extract polyphenols from
      eggplant entire fruit, pulp, or skin, both fresh and dry, and compare results
      between conventional extraction and microwave-assisted extraction (MAE). The
      effects of time exposure (15, 30, 60, and 90 min) and solvent (water 100% or
      ethanol/water 50%) were also evaluated. The highest amount of polyphenols was
      found in the extract obtained from dry peeled skin treated with 50% aqueous
      ethanol, irradiated with microwave; this extract contained also high quantity of
      flavonoids and showed good antioxidant activity expressed by its capacity to
      scavenge superoxide anion and to inhibit lipid peroxidation.

PMID- 24683355
TI  - Scheduling projects with multiskill learning effect.
AB  - We investigate the project scheduling problem with multiskill learning effect. A
      new model is proposed to deal with the problem, where both autonomous and induced
      learning are considered. In order to obtain the optimal solution, a genetic
      algorithm with specific encoding and decoding schemes is introduced. A numerical
      example is used to illustrate the proposed model. The computational results show
      that the learning effect cannot be neglected in project scheduling. By means of
      determining the level of induced learning, the project manager can balance the
      project makespan with total cost. 

PMID- 24683356
TI  - A systematic comparison of data selection criteria for SMT domain adaptation.
AB  - Data selection has shown significant improvements in effective use of training
      data by extracting sentences from large general-domain corpora to adapt
      statistical machine translation (SMT) systems to in-domain data. This paper
      performs an in-depth analysis of three different sentence selection techniques.
      The first one is cosine tf-idf, which comes from the realm of information
      retrieval (IR). The second is perplexity-based approach, which can be found in
      the field of language modeling. These two data selection techniques applied to
      SMT have been already presented in the literature. However, edit distance for
      this task is proposed in this paper for the first time. After investigating the
      individual model, a combination of all three techniques is proposed at both
      corpus level and model level. Comparative experiments are conducted on Hong Kong
      law Chinese-English corpus and the results indicate the following: (i) the
      constraint degree of similarity measuring is not monotonically related to domain
      specific translation quality; (ii) the individual selection models fail to
      perform effectively and robustly; but (iii) bilingual resources and combination
      methods are helpful to balance out-of-vocabulary (OOV) and irrelevant data; (iv)
      finally, our method achieves the goal to consistently boost the overall
      translation performance that can ensure optimal quality of a real-life SMT
      system. 

PMID- 24683357
TI  - On the singular perturbations for fractional differential equation.
AB  - The goal of this paper is to examine the possible extension of the singular
      perturbation differential equation to the concept of fractional order derivative.
      To achieve this, we presented a review of the concept of fractional calculus. We
      make use of the Laplace transform operator to derive exact solution of singular
      perturbation fractional linear differential equations. We make use of the
      methodology of three analytical methods to present exact and approximate solution
      of the singular perturbation fractional, nonlinear, nonhomogeneous differential
      equation. These methods are including the regular perturbation method, the new
      development of the variational iteration method, and the homotopy decomposition
      method. 

PMID- 24683358
TI  - Potent antioxidative and UVB protective effect of water extract of Eclipta
      prostrata L.
AB  - Oxidative stress, including Ultraviolet (UV) irradiation-induced skin damage, is
      involved in numerous diseases. This study demonstrates that water extract of
      Eclipta prostrata L. (WEP) has a potent effect in scavenging 1,1-diphenyl-2
      picrylhydrazyl (DPPH), superoxide radicals, and chelating ferrous ion, exhibiting
      IC50 values of 0.23 mg/mL, 0.48 mg/mL, and 1.25 mg/mL, respectively. The WEP
      total phenol content was 176.45 mg gallic acid equivalents (GAE)/g sample.
      Chlorogenic acid, a component of the plant's active ingredients, was determined
      by HPLC and antioxidative assay. However, no caffeic acid, stigmasterol, or
      wedelolactone was present in WEP. WEP absorbs both UVA and UVB irradiation, and
      furthermore, the extract shows a dose-dependent response in the protection of
      HaCaT human keratinocytes and mouse fibroblasts 3T3 cells against UVB-induced
      cytotoxicity, which may result from a synergistic effect between chlorogenic acid
      and other active components present in WEP.

PMID- 24683359
TI  - The inhibitory effect of a novel polypeptide fraction from Arca subcrenata on
      cancer-related inflammation in human cervical cancer HeLa cells.
AB  - Inflammation is known to be closely associated with the development of cancer.
      The study was launched in human cervical cancer HeLa cells to investigate the
      antitumor and anti-inflammatory effects of P2, a marine polypeptide fraction from
      an important fishery resource Arca subcrenata. The basic research showed that P2
      could suppress the production of nitric oxide in LPS-induced RAW264.7 macrophage
      cells as well as the secretion of inflammatory cytokines IL-6 and TNF- alpha in
      human cervical cancer HeLa cells. For the molecular mechanisms, P2 was shown to
      downregulate the gene expression of proinflammatory cytokines IL-6 and IL-8 and
      to inhibit the COX-2 and iNOS-related pathways in HeLa cells. In consequence, P2
      might inhibit tumor development by blocking the interaction between tumor
      microenvironment and proinflammatory mediators. All findings indicate that P2
      possesses the potential to be developed as a novel agent for cancer therapy. 

PMID- 24683360
TI  - Harmful algae records in Venice lagoon and in Po River Delta (northern Adriatic
      Sea, Italy).
AB  - A detailed review of harmful algal blooms (HAB) in northern Adriatic Sea lagoons
      (Po River Delta and Venice lagoon) is presented to provide "updated reference
      conditions" for future research and monitoring activities. In the study areas,
      the high mollusc production requires the necessity to identify better methods
      able to prevent risks for human health and socioeconomical interests. So, an
      integrated approach for the identification and quantification of algal toxins is
      presented by combining microscopy techniques with Liquid Chromatography coupled
      with High Resolution Time of Flight Mass Spectrometry (HPLC-HR-TOF-MS). The
      method efficiency was first tested on some samples from the mentioned coastal
      areas, where Dinophysis spp. occurred during summer in the sites directly
      affected by seawaters. Although cell abundance was always <200 cells/L, the
      presence of Pectenotoxin-2 (PTX2), detected by HPLC-HR-TOF-MS, indicated the
      potential release of detectable amounts of toxins even at low cell abundance.

PMID- 24683361
TI  - Antioxidant capacity and total phenolic content in fruit tissues from accessions
      of Capsicum chinense Jacq. (Habanero pepper) at different stages of ripening.
AB  - In the past few years, there has been a renewed interest in studying a wide
      variety of food products that show beneficial effects on human health. Capsicum
      is an important agricultural crop, not only because its economic importance, but
      also for the nutritional values of its pods, mainly due to the fact that they are
      an excellent source of antioxidant compounds, and also of specific constituents
      such as the pungent capsaicinoids localized in the placental tissue. This current
      study was designed to evaluate the antioxidant capacity and total phenolic
      contents from fruits tissues of two Capsicum chinense accessions, namely, Chak
      k'an-iik (orange) and MR8H (red), at contrasting maturation stages. Results
      showed that red immature placental tissue, with a Trolox equivalent antioxidant
      capacity (TEAC) value of 55.59 MUmols TE g(-1) FW, exhibited the strongest total
      antioxidant capacity using both the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the
      CUPRAC methods. Placental tissue also had the highest total phenolic content (27
      g GAE 100 g(-1) FW). The antioxidant capacity of Capsicum was directly related to
      the total amount of phenolic compounds detected. In particular, placentas had
      high levels of capsaicinoids, which might be the principal responsible for their
      strong antioxidant activities.

PMID- 24683362
TI  - On the degrees of freedom of interference alignment for multicell MIMO
      interfering broadcast channels.
AB  - The interference alignment (IA) is a promising technique to efficiently mitigate
      interference and to enhance capacity of a wireless network. This paper proposes
      an interference alignment scheme for a cellular network with L cells and K users
      under a multiple-input multiple-output (MIMO) Gaussian interfering broadcast
      channel (IFBC) scenario. The proposed IA scheme aligns intercell interferences
      (ICI) into a small dimensional subspace through a cooperative receive beamforming
      and cancels both the ICI and interuser interferences (IUI) simultaneously through
      a transmit beamforming. We characterize the feasibility condition for the
      proposed IA to achieve a total number of degrees of freedom (DoF) of LK in terms
      of the numbers of transmit antennas and receive antennas. Then we derive the
      maximum number of DoF achieved by the proposed IA by finding an optimal dimension
      of ICI alignment subspace for a given antenna configuration. The numerical
      results show that the proposed IA scheme has a better DoF performance than the
      conventional schemes. 

PMID- 24683363
TI  - Some properties of solutions of a functional-differential equation of second
      order with delay.
AB  - Existence, uniqueness, data dependence (monotony, continuity, and
      differentiability with respect to parameter), and Ulam-Hyers stability results
      for the solutions of a system of functional-differential equations with delays
      are proved. The techniques used are Perov's fixed point theorem and weakly Picard
      operator theory. 

PMID- 24683364
TI  - Urban-rural disparity of generics prescription in Taiwan: the example of
      dihydropyridine derivatives.
AB  - The aim of the current study was to investigate the urban-rural disparity of
      prescribing generics, which were usually cheaper than branded drugs, within the
      universal health insurance system in Taiwan. Data sources were the cohort
      datasets of National Health Insurance Research Database with claims data in 2010.
      The generic prescribing ratios of dihydropyridine (DHP) derivatives (the
      proportion of DHP prescribed as generics to all prescribed DHP) of medical
      facilities were examined against the urbanization levels of the clinic location.
      Among the total 21,606,914 defined daily doses of DHP, 35.7% belonged to
      generics. The aggregate generic prescribing ratio rose from 6.7% at academic
      medical centers to 15.3% at regional hospitals, 29.4% at community hospital, and
      66.1% at physician clinics. Among physician clinics, the generic prescribing
      ratio in urban areas was 63.9 +/- 41.0% (mean +/- standard deviation), lower than
      that in suburban (69.6 +/- 38.7%) and in rural (74.1% +/- 35.3%). After adjusting
      the related factors in the linear regression model, generic prescribing ratios of
      suburban and rural clinics were significantly higher than those of urban clinics
      (beta = 0.043 and 0.077; P = 0.024 and 0.008, resp.). The generic prescribing
      ratio of the most popular antihypertensive agents at a clinic was reversely
      associated with the urbanization level. 

PMID- 24683366
TI  - A Five Step Process for Interactive Parent-Adolescent Communication About HIV
      Prevention: Advice from Parents Living With HIV/AIDS.
AB  - AIM: This study investigated how parents living with HIV communicated about HIV
      prevention with their 10-18 year old children. METHODS: Interviews with 76
      mothers and fathers were analyzed for (1) their experiences discussing HIV
      prevention with adolescents, and (2) advice on how to best broach HIV-related
      topics. RESULTS: Interactive conversations, where both parents and adolescents
      participated, were regarded as effective. Parents emphasized that adolescents
      should have a "voice" (be able to voice their concerns) and a "choice" (have a
      variety of effective prevention strategies to choose from) during HIV-related
      talks. DISCUSSION: A five step process for interactive communication emerged as a
      result of these discussions. IMPLICATIONS: Health care professionals can
      facilitate adolescent sexual health by encouraging parents to actively involve
      their children in discussions about HIV prevention. CONCLUSION: Future HIV
      prevention programs could benefit by providing parents with appropriate tools to
      foster interactive discussions about sexual health with adolescents.

PMID- 24683365
TI  - Purslane weed (Portulaca oleracea): a prospective plant source of nutrition,
      omega-3 fatty acid, and antioxidant attributes.
AB  - Purslane (Portulaca oleracea L.) is an important plant naturally found as a weed
      in field crops and lawns. Purslane is widely distributed around the globe and is
      popular as a potherb in many areas of Europe, Asia, and the Mediterranean region.
      This plant possesses mucilaginous substances which are of medicinal importance.
      It is a rich source of potassium (494 mg/100 g) followed by magnesium (68 mg/100
      g) and calcium (65 mg/100 g) and possesses the potential to be used as vegetable
      source of omega-3 fatty acid. It is very good source of alpha-linolenic acid
      (ALA) and gamma-linolenic acid (LNA, 18 : 3 w3) (4 mg/g fresh weight) of any
      green leafy vegetable. It contained the highest amount (22.2 mg and 130 mg per
      100 g of fresh and dry weight, resp.) of alpha-tocopherol and ascorbic acid (26.6
      mg and 506 mg per 100 g of fresh and dry weight, resp.). The oxalate content of
      purslane leaves was reported as 671-869 mg/100 g fresh weight. The antioxidant
      content and nutritional value of purslane are important for human consumption. It
      revealed tremendous nutritional potential and has indicated the potential use of
      this herb for the future.

PMID- 24683367
TI  - The CKC Challenge: Exploring Tools for Collaborative Knowledge Construction.
AB  - The great success of Web 2.0 is mainly fuelled by an infrastructure that allows
      web users to create, share, tag, and connect content and knowledge easily. The
      tools for developing structured knowledge in this manner have started to appear
      as well. However, there are few, if any, user studies that are aimed at
      understanding what users expect from such tools, what works and what doesn't. We
      organized the Collaborative Knowledge Construction (CKC) Challenge to assess the
      state of the art for the tools that support collaborative processes for creation
      of various forms of structured knowledge. The goal of the Challenge was to get
      users to try out different tools and to learn what users expect from such tools
      features that users need, features that they like or dislike. The Challenge task
      was to construct structured knowledge for a portal that would provide information
      about research. The Challenge design contained several incentives for users to
      participate. Forty-nine users registered for the Challenge; thirty-three of them
      participated actively by using the tools. We collected extensive feedback from
      the users where they discussed their thoughts on all the tools that they tried.
      In this paper, we present the results of the Challenge, discuss the features that
      users expect from tools for collaborative knowledge constructions, the features
      on which Challenge participants disagreed, and the lessons that we learned.

PMID- 24683368
TI  - The Circuit Theory Behind Coupled-Mode Magnetic Resonance-Based Wireless Power
      Transmission.
AB  - Inductive coupling is a viable scheme to wirelessly energize devices with a wide
      range of power requirements from nanowatts in radio frequency identification tags
      to milliwatts in implantable microelectronic devices, watts in mobile
      electronics, and kilowatts in electric cars. Several analytical methods for
      estimating the power transfer efficiency (PTE) across inductive power
      transmission links have been devised based on circuit and electromagnetic
      theories by electrical engineers and physicists, respectively. However, a direct
      side-by-side comparison between these two approaches is lacking. Here, we have
      analyzed the PTE of a pair of capacitively loaded inductors via reflected load
      theory (RLT) and compared it with a method known as coupled-mode theory (CMT). We
      have also derived PTE equations for multiple capacitively loaded inductors based
      on both RLT and CMT. We have proven that both methods basically result in the
      same set of equations in steady state and either method can be applied for short-
      or midrange coupling conditions. We have verified the accuracy of both methods
      through measurements, and also analyzed the transient response of a pair of
      capacitively loaded inductors. Our analysis shows that the CMT is only applicable
      to coils with high quality factor (Q) and large coupling distance. It simplifies
      the analysis by reducing the order of the differential equations by half compared
      to the circuit theory.

PMID- 24683369
TI  - Computing Clinically Relevant Binding Free Energies of HIV-1 Protease Inhibitors.
AB  - The use of molecular simulation to estimate the strength of macromolecular
      binding free energies is becoming increasingly widespread, with goals ranging
      from lead optimization and enrichment in drug discovery to personalizing or
      stratifying treatment regimes. In order to realize the potential of such
      approaches to predict new results, not merely to explain previous experimental
      findings, it is necessary that the methods used are reliable and accurate, and
      that their limitations are thoroughly understood. However, the computational cost
      of atomistic simulation techniques such as molecular dynamics (MD) has meant that
      until recently little work has focused on validating and verifying the available
      free energy methodologies, with the consequence that many of the results
      published in the literature are not reproducible. Here, we present a detailed
      analysis of two of the most popular approximate methods for calculating binding
      free energies from molecular simulations, molecular mechanics Poisson-Boltzmann
      surface area (MMPBSA) and molecular mechanics generalized Born surface area
      (MMGBSA), applied to the nine FDA-approved HIV-1 protease inhibitors. Our results
      show that the values obtained from replica simulations of the same protease-drug
      complex, differing only in initially assigned atom velocities, can vary by as
      much as 10 kcal mol-1, which is greater than the difference between the best and
      worst binding inhibitors under investigation. Despite this, analysis of ensembles
      of simulations producing 50 trajectories of 4 ns duration leads to well converged
      free energy estimates. For seven inhibitors, we find that with correctly
      converged normal mode estimates of the configurational entropy, we can correctly
      distinguish inhibitors in agreement with experimental data for both the MMPBSA
      and MMGBSA methods and thus have the ability to rank the efficacy of binding of
      this selection of drugs to the protease (no account is made for free energy
      penalties associated with protein distortion leading to the over estimation of
      the binding strength of the two largest inhibitors ritonavir and atazanavir). We
      obtain improved rankings and estimates of the relative binding strengths of the
      drugs by using a novel combination of MMPBSA/MMGBSA with normal mode entropy
      estimates and the free energy of association calculated directly from simulation
      trajectories. Our work provides a thorough assessment of what is required to
      produce converged and hence reliable free energies for protein-ligand binding.

PMID- 24683371
TI  - Letter from the editor.

PMID- 24683370
TI  - Efficient Parameter Estimation of Generalizable Coarse-Grained Protein Force
      Fields Using Contrastive Divergence: A Maximum Likelihood Approach.
AB  - Maximum Likelihood (ML) optimization schemes are widely used for parameter
      inference. They maximize the likelihood of some experimentally observed data,
      with respect to the model parameters iteratively, following the gradient of the
      logarithm of the likelihood. Here, we employ a ML inference scheme to infer a
      generalizable, physics-based coarse-grained protein model (which includes Go-like
      biasing terms to stabilize secondary structure elements in room-temperature
      simulations), using native conformations of a training set of proteins as the
      observed data. Contrastive divergence, a novel statistical machine learning
      technique, is used to efficiently approximate the direction of the gradient
      ascent, which enables the use of a large training set of proteins. Unlike
      previous work, the generalizability of the protein model allows the folding of
      peptides and a protein (protein G) which are not part of the training set. We
      compare the same force field with different van der Waals (vdW) potential forms:
      a hard cutoff model, and a Lennard-Jones (LJ) potential with vdW parameters
      inferred or adopted from the CHARMM or AMBER force fields. Simulations of
      peptides and protein G show that the LJ model with inferred parameters
      outperforms the hard cutoff potential, which is consistent with previous
      observations. Simulations using the LJ potential with inferred vdW parameters
      also outperforms the protein models with adopted vdW parameter values,
      demonstrating that model parameters generally cannot be used with force fields
      with different energy functions. The software is available at
      https://sites.google.com/site/crankite/.

PMID- 24683372
TI  - Linaclotide: a novel therapy for chronic constipation and constipation
      predominant irritable bowel syndrome.
AB  - Chronic constipation and irritable bowel syndrome (IBS) are functional
      gastrointestinal disorders that significantly affect patients' quality of life.
      Chronic constipation and IBS are prevalent-1 2% of the US population meet the
      diagnostic criteria for IBS, and 1 5% meet the criteria for chronic constipation-
      and these conditions negatively impact the healthcare system from an economic
      perspective. Despite attempts at dietary modification, exercise, or use of over
      the-counter medications, many patients have persistent symptoms. Alternative
      treatment options are limited. This article describes linaclotide (Linzess,
      Ironwood Pharmaceuticals/Forest Pharmaceuticals), a new, first-in-class
      medication for the treatment of chronic constipation and constipation-predominant
      IBS. 

PMID- 24683374
TI  - Diagnosis and treatment of inflammatory bowel disease in older patients.

PMID- 24683373
TI  - Noninvasive Diagnosis of NASH and Liver Fibrosis Within the Spectrum of NAFLD.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver
      disease in the United States, affecting an estimated 70 million Americans. The
      histologic spectrum of NAFLD ranges from simple steatosis to nonalcoholic
      steatohepatitis (NASH), fibrosis, and eventually cirrhosis. Patients with NASH
      and significant fibrosis seen on liver biopsy have an increased risk for liver
      related morbidity and mortality compared to patients with simple steatosis. Due
      to the high prevalence of NAFLD, there has been an urgent need to develop
      reliable noninvasive markers and tests that can accurately predict the presence
      of advanced disease without the need for liver biopsy. These tests can be divided
      into 2 groups: those that predict the presence of NASH (such as markers of
      hepatocyte apoptosis, oxidative stress, and inflammation, as well as predictive
      models based on clinical variables) and those that predict the presence of
      fibrosis (such as simple and complex predictive models). This paper provides an
      overview of various noninvasive methods for detecting NAFLD and suggests a
      diagnostic algorithm that can be used in clinical practice. 

PMID- 24683375
TI  - Protease inhibitor-based therapy for hepatitis C virus infection-why wait?

PMID- 24683376
TI  - Use of endoscopic ultrasound for management of severe, refractory
      gastrointestinal bleeding.

PMID- 24683377
TI  - Management of eosinophilic esophagitis from childhood to adulthood.

PMID- 24683378
TI  - Nutritional assessment of patients with chronic liver disease.

PMID- 24683379
TI  - Metastatic amelanotic melanoma of the jejunum diagnosed on capsule endoscopy.

PMID- 24683380
TI  - Capsule endoscopy for management of small bowel melanoma-is it time yet?

PMID- 24683381
TI  - Refractory pancolitis: a novel presentation of idiopathic myointimal hyperplasia
      of mesenteric veins.

PMID- 24683382
TI  - Idiopathic myointimal hyperplasia of mesenteric veins.

PMID- 24683383
TI  - Employment Satisfaction and Health Outcomes among Professional Iraqi refugees as
      compared to Immigrants.
AB  - This study investigates employment and health outcomes in Iraqi refugees compared
      to Iraqi immigrants. We surveyed 148 Iraqi professional refugees and 111 Iraqi
      professional immigrants residing in the U.S. We hypothesized that Iraqi refugees
      would report lower employment and worse self-rated health as compared to Iraqi
      immigrants. Logistic Regression was used to test various models. Results showed
      that more immigrants were employed, as well as employed in their original
      profession as compared to refugees. Regardless of immigration status,
      participants' age and the way they rated their job played a larger role in
      health. The study is the first to demonstrate that, controlling for professional,
      ethnic and cultural background, there are unknown mechanisms resulting in lower
      employment and skilled employment in refugees as compared to matched immigrant
      controls. Furthermore, satisfaction with the new work appears more important than
      employment per se.

PMID- 24683384
TI  - Synthesis and Crystal Structure of the Bioinorganic Complex [Sb(Hedta)].2H2O.
AB  - The antimony(III) complex [Sb(Hedta)].2H2O was synthesized with
      ethylenediaminetetraacetic acid (H4edta) and antimonous oxide as main raw
      materials in aqueous solution. The composition and structure of the complex were
      characterized by elemental analysis, infrared spectra, single crystal X-ray
      diffraction, X-ray powder diffraction, thermogravimetry, and differential
      scanning calorimetry. The crystal structure of the antimony(III) complex belongs
      to orthorhombic system, space group Pna2(1), with cell parameters of a =
      18.4823(18) A, b = 10.9408(12) A, c = 7.3671(5) A, V = 1489.7(2) A(3), Z = 4, and
      D c = 1.993 g cm(-3). The Sb(III) ion is five-coordinated by two amido N atoms
      and three carboxyl O atoms from a single Hedta(3-) ligand, forming a distorted
      trigonal bipyramid geometry. The thermal decomposition processes of the complex
      include dehydration, oxidation, and pyrolysis of the ligand, and the last residue
      is Sb2O3 at the temperature of 570 degrees C. 

PMID- 24683385
TI  - Parasites: what are they good for?
AB  - Parasitic diseases caused by helminth and protozoan infections remain one of the
      largest global public health problems for mankind. While natural immunity in man
      is rare or slow to develop for many parasites, the immune response is capable of
      recognizing and responding to infection by utilizing a number of different
      immunological mechanisms. This special topics journal issue examines many of the
      key findings in the recent literature regarding the immune response against
      helminth and protozoan infections, as well as highlighting areas in which our
      current knowledge falls short. The question of how we can tailor immune responses
      to prevent or reduce disease burden is a burning question within the field of
      immunoparasitology.

PMID- 24683386
TI  - Recent advances in tuberculosis: New drugs and treatment regimens.
AB  - The current treatment regimen against drug susceptible tuberculosis (DS-TB) was
      defined by the 1980s. Since then the emergence of the global HIV pandemic and the
      escalation of drug resistant (DR-) forms of TB have presented new challenges for
      therapeutic research. Priority goals include shortening DS-TB treatment,
      improving DR-TB treatment and making combined TB-HIV therapy easier. To help
      achieve these goals, a range of new drugs and treatment strategies are currently
      being evaluated. Phase IIb and III clinical trials are ongoing to assess
      combinations involving the high-dose rifamycins, the 8-methoxyquinolones, a
      diarylquinoline (bedaquiline) and the nitroimidazoles. Other compounds (e.g.
      novel oxazolidinones and ethylenediamines) are at earlier stages of clinical
      development. Overall, there are grounds for optimism that recent advances will
      contribute towards achievement of new treatment regimens in the foreseeable
      future. However, long-term investment, political commitment and scientific
      endeavour are crucial to ensure that progress is sustained and the benefits of
      recent advances reach those in the greatest need.

PMID- 24683387
TI  - Beyond Thymidylate Synthase and Dihydrofolate Reductase: Impact of Non-coding
      microRNAs in Anticancer Chemoresistance.
AB  - Chemoresistance is one of the major reasons for the failure of anticancer
      chemotherapy in treating advanced stage cancer. The mechanism of chemoresistance
      to fluoropyrimidines and antifolates has been extensively investigated in the
      past 40 years. It has been well established that thymidylate synthase (TYMS, TS)
      and dihydrofolate reductase (DHFR) are two major targets for fluoropyrimidines
      and antifolates, respectively. The regulatory mechanism of TS and DHFR expression
      is rather complex involving transcriptional, post-transcriptional and
      translational regulations. Our recent understanding of the chemoresistance
      mechanism has been extended beyond the simple one target/drug view. In this
      review, we will focus on the recent advancement of non-coding microRNAs (miRNAs)
      in contributing to the regulations of TS and DHFR expression, and to the
      chemoresistance mechanism of fluoropyrimidines and antifolates.

PMID- 24683388
TI  - Identification of Marker Genes for Cancer Based on Microarrays Using a
      Computational Biology Approach.
AB  - Rapid advances in gene expression microarray technology have enabled to discover
      molecular markers used for cancer diagnosis, prognosis, and prediction. One
      computational challenge with using microarray data analysis to create cancer
      classifiers is how to effectively deal with microarray data which are composed of
      high-dimensional attributes (p) and low-dimensional instances (n). Gene selection
      and classifier construction are two key issues concerned with this topics. In
      this article, we reviewed major methods for computational identification of
      cancer marker genes. We concluded that simple methods should be preferred to
      complicated ones for their interpretability and applicability.

PMID- 24683389
TI  - Topology Based Selection and Curation of Level Sets.
AB  - The selection of appropriate level sets for the quantitative visualization of
      three dimensional imaging or simulation data is a problem that is both
      fundamental and essential. The selected level set needs to satisfy several
      topological and geometric constraints to be useful for subsequent quantitative
      processing and visualization. For an initial selection of an isosurface, guided
      by contour tree data structures, we detect the topological features by computing
      stable and unstable manifolds of the critical points of the distance function
      induced by the isosurface. We further enhance the description of these features
      by associating geometric attributes with them. We then rank the attributed
      features and provide a handle to them for curation of the topological anomalies.

PMID- 24683390
TI  - Loss of asthma control after cessation of omalizumab treatment: real life data.
AB  - INTRODUCTION: Many clinical and observational studies have demonstrated
      effectiveness of omalizumab (OMA) in the treatment of severe asthma, but the
      optimal duration of the therapy remains unknown. AIM: The article presents the
      authors' clinical experience on OMA cessation in routine practice. MATERIAL AND
      METHODS: Due to new reimbursement criteria, OMA therapy has been interrupted in
      11 subjects (6 women/5 men). The mean age of patients was 50.73 +/-14.16 years,
      the mean time of severe asthma duration was 13.54 +/-6.05 years. All of them had
      an excellent/good response to OMA. The duration of OMA therapy was 67.73 +/-11.64
      months. RESULTS: Nine out of 11 patients had severe asthma exacerbation within
      the first 5 months after the OMA withdrawal. The mean time to the first severe
      exacerbation was 7.56 +/-2.67 weeks. Between the time of OMA cessation and the
      time of reassessment, the mean score of Asthma Control Questionnaire increased
      from 2.58 +/-0.71 to 3.63 +/-1.26 points and the mean score of Asthma Quality of
      Life Questionnaire decreased from 4.3 +/-1.91 to 3.18 +/-1.17 points. The mean
      oral corticosteroids (OCS) dose increased from 4.61 +/-3.0 mg/day to 33.33 +/
      13.12 mg/day. The number of exacerbations within the last 12 months increased
      from 1.6 +/-0.67 to 5.2 +/-1.4, and the number of hospitalizations or emergency
      room (ER) attendence increased from 0.11 +/-0.31 to 1.56 +/-1.26. CONCLUSIONS:
      These data indicate that the withdrawal of OMA therapy after the successful long
      term therapy may cause severe asthma exacerbations. Therefore, the decision
      regarding cessation of OMA treatment should be undertaken individually after
      careful weighing benefits and risks, especially in patients with a long history
      of severe asthma, treated with high doses of OCS before OMA introduction, near
      fatal asthma events and/or aggravation of asthma during previous episodes of
      interruptions in OMA treatment.

PMID- 24683391
TI  - Assessment of skin microcirculation by laser Doppler flowmetry in systemic
      sclerosis patients.
AB  - INTRODUCTION: First lesions to occur in the course of systemic sclerosis (SSc)
      involve microcirculation. AIM: The study involved assessment of the suitability
      of laser Doppler flowmetry (LDF) in examination of the performance of skin
      microcirculation in the distal portion of the upper extremity in SSc patients.
      MATERIAL AND METHODS: Overall the study involved 27 patients with systemic
      sclerosis. The control group comprised age - and gender-matched 27 healthy
      individuals. All the study subjects underwent microcirculation perfusion
      measurement at rest (rest flow - RF) as well as microcirculatory flow challenge
      tests - reactive hyperaemia test (RHT) and thermal stimulation test (TST).
      RESULTS: The study did not show any differences in the skin microcirculation
      perfusion at rest between the test group and the control, while reactive
      hyperaemia test results revealed significantly lower skin microcirculation
      perfusion values during the cuff inflation in SSc patients, as compared to the
      controls. In the test group, a lower perfusion value was observed during
      secondary hyperaemia following cuff release. Comparative analysis of skin
      microcirculation perfusion changes during the thermal stimulation test revealed a
      significantly lower change of the perfusion value and longer time of return to
      the baseline in the test group as compared to the control group. CONCLUSIONS: The
      study performed has shown the suitability of LDF in the assessment of the
      microangiopathy degree in systemic sclerosis patients. The skin perfusion value
      in SSc patients should be assessed on the basis of parameters obtained in
      microcirculation challenge tests.

PMID- 24683392
TI  - The Polish version of Skindex-29: psychometric properties of an instrument to
      measure quality of life in dermatology.
AB  - INTRODUCTION: Skin conditions have a negative impact on quality of life and it is
      necessary to quantify this impact. Skindex-29 is a self-report questionnaire
      developed to measure dermatology-specific quality of life. AIM: The objective of
      this study is to adapt this questionnaire to Polish conditions. The adaptation
      procedure involved the works on the linguistic content of the items and testing
      psychometric properties of the Polish version of Skindex-29, including item
      characteristics, factorial structure, aspects of reliability and validity.
      MATERIAL AND METHODS: Two-hundred and ninety patients (63.4% women and 35.2% men)
      suffering from a range of skin conditions were recruited from several
      dermatological out-patient and in-patient clinics in Poland. Quality of life was
      measured using Skindex-29 and appropriate clinical data were collected. RESULTS:
      The global score of Skindex-29 showed the normal distribution. Cronbach's alpha
      reliability coefficients were found to be high to very high for all Skindex-29
      indexes. Factor analysis yielded four factors, in contrast to the original
      version of the questionnaire, for which a three-factor solution had been
      reported. Skindex-29 validity was demonstrated by showing the differences in the
      quality of life scores across different diagnostic categories, and between in
      patients and out-patients. Skindex-29 global scores were found to be
      significantly predicted by the localization of the skin lesions on legs,
      anogenital areas and palms. CONCLUSIONS: The findings of this study support
      reliability and validity of the Polish version of Skindex-29, but they also raise
      questions to its three-factor structure.

PMID- 24683393
TI  - Pro-inflammatory cytokines in patients with various kinds of acne treated with
      isotretinoin.
AB  - INTRODUCTION: Acne vulgaris is the most frequently diagnosed dermatosis in
      patients aged between 11 and 30. It is believed that it affects about 80% of
      persons in this age group or even, taking into account lesions of low intensity,
      100% of young people. The role of cytokines in the pathogenesis of acne is not
      fully known. The TLR2 receptors play a role in the aetiology of acne. Stimulation
      of TLR2 by Propionibacterium acnes makes the IL-8 and IL-12 concentrations
      increase. AIM: The aim of this work was to determine IL-1beta, IL-1alpha, IL-8
      and TNF-alpha levels in patients' sera used to test response to TLR2 stimulation.
      A decrease in the levels of the above mentioned cytokines together with a
      decrease in sebum production were defined as an indication of efficient treatment
      with isotretinoin. MATERIAL AND METHODS: The tests were performed in 155 patients
      treated for different clinical forms of acne with an oral isotretinoin
      preparation in the Dermatology Clinic of the Silesian Medical University in
      Katowice in 2009-2011 - I group and the patients treated with oral isotretinoin 2
      and 5 years ago - II group. The control group consisted of 40 healthy
      individuals. CONCLUSIONS: Measurements of IL-1alpha, IL-1beta and TNF-alpha sera
      concentrations could be assessed in parallel to the improvement of the clinical
      condition and can constitute a good indication of the efficiency of the
      isotretinoin treatment.

PMID- 24683394
TI  - Influence of ustekinumab on body weight of patients with psoriasis: an initial
      report.
AB  - INTRODUCTION: Many recent epidemiological studies have shown the influence of
      treatment with anti-TNF-alpha on body mass of patients with psoriasis but there
      are no reports in the literature on the influence of ustekinumab on that
      parameter. AIM: To review the effect of ustekinumab therapy on body weight in
      patients with psoriasis. MATERIAL AND METHODS: The examined group consisted of 11
      patients with psoriasis treated at the Department and Clinic of Dermatology in
      Olsztyn. Patients' body mass and body mass index (BMI) were evaluated prior to
      the first administration of the ustekinumab dose and at week 28 of treatment (the
      day of the fourth dose). RESULTS: Body mass increase was determined in 7 patients
      (64%), on average by 2.27 kg (p < 0.05), and the BMI increased by 3.35% (p <
      0.1). CONCLUSIONS: Observing a correlation between ustekinumab application and
      body mass increase, similar to the treatment with anti-TNF-alpha preparations, an
      attempt was undertaken at explaining that correlation by analysing the role of IL
      12 and IL-23 in psoriasis pathogenesis. IL-12 and IL-23, by influencing the naive
      lymphocytes T and stimulating their diversification towards Th1 and Th17, also,
      indirectly, cause an increase in TNF-alpha and other cytokines production (IL-2,
      IFN-gamma, IL-17, IL-10, IL-22). Ustekinumab will then have a significant
      influence on decreasing the production of cytokines, which are important for
      metabolism and body mass.

PMID- 24683395
TI  - Omalizumab in an allergology clinic: real life experience and future
      developments.
AB  - Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of
      circulating IgE and expression of IgE high affinity receptor (FCERI) on mast
      cells and basophils. Its role in the therapy of allergic asthma and urticaria is
      well established. According to GINA guidelines, omalizumab should be considered
      as an important alternative to systemic corticosteroids in uncontrolled asthma.
      Several ongoing trials will evaluate omalizumab efficacy in the treatment of
      other allergic diseases and conditions. Further studies are needed to answer
      several practical questions on the optimal duration of treatment and possible
      biomarkers to predefine a cohort of responders to this therapy. 

PMID- 24683396
TI  - Omalizumab treatment in brittle asthma.
AB  - Asthma is a heterogeneous disease with variable characteristics such as lung
      function, symptoms and control, body weight, pattern of inflammation, and
      response to treatment. Brittle asthma is one of clinical phenotypes of asthma
      with unclear pathogenic mechanisms and appropriate treatment. Analysis of 2
      described cases suggests that omalizumab could be useful in the treatment of
      brittle allergic asthma. 

PMID- 24683397
TI  - Effectiveness of omalizumab in a patient with a life-threatening episode of
      bronchospasm and larynx angioedema after exposure to house dust.
AB  - Omalizumab is a monoclonal antibody against IgE, nowadays approved for the
      treatment of persistent severe (EU) or moderate-to severe (USA) IgE-mediated
      asthma but there is also some evidence (case reports and four published clinical
      trials) on the effectiveness of this medication in urticaria and angioedema. The
      case of a 42-year-old woman suffering from severe allergic asthma and severe
      chronic urticaria with concomitant angioedema is presented in the article. She
      had a life-threatening episode of bronchospasm and larynx edema after exposure to
      house dust recorded in her medical history. The patient did not respond to
      standard therapy. The improvement in asthma control and remission of chronic
      urticaria and angioedema was achieved after introducing the therapy with
      omalizumab. 

PMID- 24683398
TI  - Omalizumab as a new therapeutic approach for children with severe asthma.
AB  - Omalizumab has been shown to improve asthma control when added to a regimen of
      guideline-based therapy for inner-city children and adolescents, nearly
      eliminating seasonal peaks in exacerbation and reducing the need for other
      medications to control asthma. Below, we describe a case of a 17-year-old non
      smoker with a history of severe asthma admitted to our clinic after unsuccessful
      10-year immunotherapy. The patient fulfilled the criteria for anti-IgE therapy,
      he was prescribed omalizumab 600 mg every 2 weeks. During therapy he was able to
      reduce his use of ICS and did not require any oral corticosteroids. He
      experienced an increase in his ability to exercise and noted no exacerbation of
      asthma symptoms. It is possible that in our patient, specific immunotherapy could
      be successfully continued after the initiation of omalizumab therapy. 

PMID- 24683399
TI  - Sweet's syndrome with idiopathic thrombocythemia.
AB  - Diagnosis of paraneoplastic skin syndromes associating neoplastic processes is
      assumed as the crucial aspect of dermatological practice. Knowledge of clinical
      findings of dermatoses suggesting coincidence of malignant proliferative
      processes facilitates diagnostic and therapeutic procedures. We would like to
      present a case of Sweet's syndrome, qualified for comparative paraneoplastic skin
      syndromes. Sweet's syndrome, acute, febrile neutrophilic dermatosis, was first
      described by Robert Douglas Sweet in 1964 as a disorder characterized by fever,
      skin lesions of erythematous-infiltrative character, leukocytosis with
      neutrophilia and dense infiltrations of dermis by mature neutrophils. Sweet's
      syndrome aetiology is not fully understood, although cytokine abnormalities
      suggest that Th1 lymphocytes play an important role in pathogenesis of the
      dermatosis. Factors inducing Sweet's syndrome include: haematopoietic
      hyperplasia; neoplasms: genitourinary, breast, gastrointestinal; infections of
      the respiratory and alimentary system; inflammatory bowel diseases; drugs;
      pregnancy and vaccinations. Systemic corticosteroids are the "gold standard" of
      Sweet's syndrome treatment; potassium iodide or colchicine may also be used.
      Indomethacin, clofazimine, cyclosporine A and sulfones are the second-line drugs.

PMID- 24683400
TI  - Pseudoporphyria induced by hemodialysis.
AB  - Pseudoporphyria is a condition identical to porphyria cutanea tarda (PCT) on
      clinical and histological grounds, but without any biochemical porphyrin
      abnormality. Excessive sunlight and UVA exposure (for example tanning beds),
      drugs such as: non-steroidal anti-inflammatory drugs, retinoids, antibiotics,
      diuretics and others are supposed to be etiological factors of pseudoporphyria.
      Cases of PCT and pseudoporphyria in patients with HCV infection and hemodialysed
      due to chronic renal failure were also described. Here, we describe a clinical
      case of a 57-year-old patient, who developed cutaneous changes on the face and
      the dorsal surfaces of hands clinically and histologically characteristic of PCT
      but with normal levels of urine porphyrins. 

PMID- 24683401
TI  - Malignant acanthosis nigricans, florid cutaneous papillomatosis and tripe palms
      syndrome associated with gastric adenocarcinoma.
AB  - Malignant acanthosis nigricans is a rare paraneoplastic skin syndrome mostly
      associated with gastric adenocarcinoma. Florid cutaneous papillomatosis and tripe
      palms syndrome are considered to be abortive clinical variants of acanthosis
      nigricans. Clinical manifestations include pruritic, hyperkeratotic and
      hyperpigmented plaques with a subsequent formation of velvety papillomas in the
      involved areas. This case report describes an unusual case of the patient
      diagnosed with a combination of malignant acanthosis nigricans, florid cutaneous
      papillomatosis and tripe palms syndrome associated with gastric adenocarcinoma. 

PMID- 24683402
TI  - Retraction: Recursive fury: conspiracist ideation in the blogosphere in response
      to research on conspiracist ideation.

PMID- 24683403
TI  - SYMPLICITY HTN-3 results to be announced: a mystery or a story foretold?

PMID- 24683404
TI  - Biosimilars: new promise for reducing healthcare costs.

PMID- 24683405
TI  - How to allocate public health manpower in township health centers in China
      scientifically and reasonably.

PMID- 24683406
TI  - A clinical perspective on mucoadhesive buccal drug delivery systems.
AB  - Mucoadhesion can be defined as a state in which two components, of which one is
      of biological origin, are held together for extended periods of time by the help
      of interfacial forces. Among the various transmucosal routes, buccal mucosa has
      excellent accessibility and relatively immobile mucosa, hence suitable for
      administration of retentive dosage form. The objective of this paper is to review
      the works done so far in the field of mucoadhesive buccal drug delivery systems
      (MBDDS), with a clinical perspective. Starting with a brief introduction of the
      mucoadhesive drug delivery systems, oral mucosa, and the theories of
      mucoadhesion, this article then proceeds to cover the works done so far in the
      field of MBDDS, categorizing them on the basis of ailments they are meant to
      cure. Additionally, we focus on the various patents, recent advancements, and
      challenges as well as the future prospects for mucoadhesive buccal drug delivery
      systems. 

PMID- 24683407
TI  - Diagnostic and prognostic value of minor elevated cardiac troponin levels for
      percutaneous coronary intervention-related myocardial injury: a prospective,
      single-center and double-blind study.
AB  - Cardiac troponin-I (cTnI) and -T (cTnT) are sensitive and specific markers of
      myocardial injury. However, the role of increased cTnI and cTnT in percutaneous
      coronary intervention (PCI)-related myocardial injury remains controversial. In
      this prospective, single-center and double-blind study, we aimed to determine the
      diagnostic and prognostic value of cTnI as well as cTnT (cTns) in PCI-related
      myocardial injury in a Chinese population. A total of 1,008 patients with stable
      angina pectoris and non-ST-segment elevation acute coronary syndrome were
      recruited. The levels of cTnI and cTnT were examined before and after PCI. All
      patients were followed up for 26+/-9 months to observe the incidence of major
      adverse cardiac events (MACEs). Our results showed that post-PCI cTnI and/or cTnT
      levels were increased to more than the 99(th) percentile upper reference limit
      (URL) in 133 (13.2%) patients, among which 22 (2.2%) were more than 5 * 99(th)
      percentile URL. By univariate analysis, an elevation in cTns after PCI was not an
      independent predictor of increased MACEs, HR 1.35 (P  =  0.33, 95%CI: 0.74-2.46).
      In conclusion, our data demonstrate that the incidence of PCI-related myocardial
      injury is not common in a Chinese population and minor elevated cTns levels may
      not be a sensitive prognostic marker for MACEs. 

PMID- 24683408
TI  - Clopidogrel improves aspirin response after off-pump coronary artery bypass
      surgery.
AB  - We sought to assess the incidence of aspirin resistance after off-pump coronary
      artery bypass (OPCAB) surgery, and investigate whether clopidogrel can improve
      aspirin response and be safely applied early after OPCAB surgery. Sixty patients
      who underwent standard OPCAB surgery were randomized into two groups. One group
      (30 patients) received mono-antiplatelet treatment (MAPT) with aspirin 100 mg
      daily and the other group received dual antiplatelet treatment (DAPT) with
      aspirin 100 mg daily plus clopidogrel 75 mg daily. Platelet aggregations in
      response to arachidonic acid (PLAA) and adenosine diphosphate (ADP) (PLADP) were
      measured preoperatively and on days 1 to 6, 8 and 10 after the antiplatelet
      agents were administered. A PLAA level above 20% was defined as aspirin
      resistance. Postoperative bleeding and other perioperative variables were also
      recorded. There were no significant differences between the two groups in
      baseline characteristics, average number of distal anastomosis, operation time,
      postoperative bleeding, ventilation time and postoperative hospital stay.
      However, the incidence of aspirin resistance was significantly lower in the DAPT
      group than that in the MAPT group on the first and second day after antiplatelet
      agents were given (62.1% vs. 32.1%, 34.5% vs. 10.7%, respectively, both P <
      0.05). There was no significant difference in postoperative complication between
      the two groups. DAPT with aspirin and clopidogrel can be safely applied to OPCAB
      patients early after the procedure. Moreover, clopidogrel reduces the incidence
      of OPCAB-related aspirin resistance. 

PMID- 24683409
TI  - Application of the back-error propagation artificial neural network (BPANN) on
      genetic variants in the PPAR-gamma and RXR-alpha gene and risk of metabolic
      syndrome in a Chinese Han population.
AB  - This study was aimed to explore the associations between the combined effects of
      several polymorphisms in the PPAR-gamma and RXR-alpha gene and environmental
      factors with the risk of metabolic syndrome by back-error propagation artificial
      neural network (BPANN). We established the model based on data gathered from
      metabolic syndrome patients (n = 1012) and normal controls (n = 1069) by BPANN.
      Mean impact value (MIV) for each input variable was calculated and the sequence
      of factors was sorted according to their absolute MIVs. Generalized multifactor
      dimensionality reduction (GMDR) confirmed a joint effect of PPAR-gamma and RXR
      alpha based on the results from BPANN. By BPANN analysis, the sequences according
      to the importance of metabolic syndrome risk factors were in the order of body
      mass index (BMI), serum adiponectin, rs4240711, gender, rs4842194, family history
      of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806,
      family history of hypertension, rs1045570, rs6537944, age, rs17817276, family
      history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no
      polymorphism was statistically significant in multiple logistic regression
      analysis. After controlling for environmental factors, A1, A2, B1 and B2
      (rs4240711, rs4842194, rs2920502 and rs3856806) models were the best models
      (cross-validation consistency 10/10, P = 0.0107) with the GMDR method. In
      conclusion, the interaction of the PPAR-gamma and RXR-alpha gene could play a
      role in susceptibility to metabolic syndrome. A more realistic model is obtained
      by using BPANN to screen out determinants of diseases of multiple etiologies like
      metabolic syndrome. 

PMID- 24683410
TI  - IRE1alpha is essential for Xenopus pancreas development.
AB  - Inositol requiring enzyme-1 (IRE1) is highly conserved from yeasts to humans.
      Upon the endoplasmic reticulum (ER) stress, IRE1 activates X-box-binding protein
      1 (XBP1) by unconventionally splicing XBP1 mRNA, which activates the unfolded
      protein response (UPR) to restore ER homeostasis. In mice, IRE1alpha inactivity
      leads to embryonic death and IRE1alpha plays an essential role in extraembryonic
      tissues and the placenta. However, its precise action in the embryo proper is
      still unknown. In this study, the loss of function analysis was performed to
      investigate the function of Xenopus IRE1alpha (xIRE1alpha) during pancreas
      development. Firstly, the complete open reading frame of xIRE1alpha was amplified
      and the expression pattern was detected. The effects of Xenopus IRE1alpha and
      XBP1 during embryo development were detected with whole-mount in situ
      hybridization. The results demonstrated that xIRE1alpha was much closer to human
      IRE1alpha when compared with their sequence alignment. xIRE1alpha was expressed
      strongly in developing pancreas and the knockdown of xIRE1alpha inhibited the
      differentiation and specification of the pancreas. xIRE1alpha, which was required
      for cytoplasmic splicing of XBP1 pre-mRNA and XBP1MO, also showed inhibitory
      effects on pancreas development. These results suggest that xIRE1alpha is
      essential for pancreas development during embryogenesis and functions via the
      XBP1 dependent pathway. 

PMID- 24683411
TI  - Naringin ameliorates acetic acid induced colitis through modulation of endogenous
      oxido-nitrosative balance and DNA damage in rats.
AB  - The aim of this study was to evaluate the effect of naringin on experimentally
      induced inflammatory bowel disease in rats. Naringin (20, 40 and 80 mg/kg) was
      given orally for 7 days to Wistar rats before induction of colitis by intrarectal
      instillation of 2 mL of 4% (v/v) acetic acid solution. The degree of colonic
      mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index
      and stool consistency. Intrarectal administration of 4% acetic acid resulted in
      significant modulation of serum alkaline phosphatase, lactate dehydrogenase,
      superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and
      myeloperoxidase (MPO) content along with colonic nitric oxide (NO), xanthine
      oxidase (XO) level and protein carbonyl content in the colonic tissue as well as
      in blood. Naringin (40 and 80 mg/kg) exerted a dose dependent (P < 0.05)
      ameliorative effect, as it significantly increased hematological parameter as
      well as colonic SOD and GSH. There was a significant (P < 0.05) and dose
      dependant inhibition of macroscopical score, ulcer area along with colonic MDA,
      MPO activity by the 7 days of pretreatment of naringin (40 and 80 mg/kg).
      Biochemical studies revealed a significant (P < 0.05) dose dependant inhibition
      in serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels by
      pretreatment of naringin. Increased levels of colonic NO, XO, protein carbonyl
      content and DNA damage were also significantly decreased by naringin
      pretreatment. The findings of the present investigation propose that naringin has
      an anti-inflammatory, anti-oxidant and anti-apoptotic potential effect at
      colorectal sites as it modulates the production and expression of oxidative
      mediators such as MDA, MPO, NO and XO, thus reducing DNA damage. 

PMID- 24683412
TI  - Rapid progression of nonculprit coronary lesions six weeks after successful
      primary PCI in culprit artery: a case report.
AB  - We report a case of a 49-year-old man who was admitted with a 3-hour history of
      sudden onset of substernal chest pain. Coronary angiography revealed that the
      left circumflex artery (LCX) was acutely and totally occluded at the mid-portion.
      In addition, the proximal and mid-portion of the right coronary artery (RCA) had
      a 60% occlusion. We inferred that the LCX was the culprit artery and primary PCI
      was successfully performed. Six weeks later, the patient had an eventful course
      with recurrence of chest pain. Coronary angiography showed no significant
      stenosis in the previous LCX lesion, while the proximal and middle potion of the
      RCA had a 90% occlusion. Our case demonstrates the systemic nature of acute
      coronary syndromes and highlights the inherent instability of coronary artery
      disease. 

PMID- 24683413
TI  - Willingness to pay in medical education.

PMID- 24683414
TI  - Green Synthesis of Robust, Biocompatible Silver Nanoparticles Using Garlic
      Extract.
AB  - This paper details a facile approach for the synthesis of stable and monodisperse
      silver nanoparticles performed at ambient/low temperature where Allium sativum
      (garlic) extract functions as the silver salt reducing agent during nanoparticle
      synthesis as well as the post-synthesis stabilizing ligands. Varying the
      synthesis conditions provides control of particle size, size-distribution, and
      kinetics of particle formation. Infrared spectroscopy, energy dispersive x-ray
      chemical analysis, and high performance liquid chromatography indicated that the
      carbohydrates present in the garlic extract are the most likely nanoparticle
      stabilizing chemistry. The synthesized silver nanoparticles also demonstrate
      potential for biomeical applications, owing to the 1) enhanced stability in
      biological media, 2) resistance to oxidation by the addition of H2O2, 3) ease and
      scalability of synthesis, and 4) lack of harsh chemicals required for synthesis.
      Cytotoxicity assays indicated no decrease in cellular proliferation for vascular
      smooth muscle cells and 3T3 fibroblasts at a concentration of 25 MUg/ml,
      confirming that garlic extract prepared silver nanoparticles are ideal candidates
      for future experimentation and implementation into biomedical applications.

PMID- 24683415
TI  - The observation report of red blood cell morphology in Thailand teenager by using
      data mining technique.
AB  - It is undeniable that laboratory information is important in healthcare in many
      ways such as management, planning, and quality improvement. Laboratory diagnosis
      and laboratory results from each patient are organized from every treatment.
      These data are useful for retrospective study exploring a relationship between
      laboratory results and diseases. By doing so, it increases efficiency in
      diagnosis and quality in laboratory report. Our study will utilize J48 algorithm,
      a data mining technique to predict abnormality in peripheral blood smear from
      1,362 students by using 13 data set of hematological parameters gathered from
      automated blood cell counter. We found that the decision tree which is created
      from the algorithm can be used as a practical guideline for RBC morphology
      prediction by using 4 hematological parameters (MCV, MCH, Hct, and RBC). The
      average prediction of RBC morphology has true positive, false positive,
      precision, recall, and accuracy of 0.940, 0.050, 0.945, 0.940, and 0.943,
      respectively. A newly found paradigm in managing medical laboratory information
      will be helpful in organizing, researching, and assisting correlation in multiple
      disciplinary other than medical science which will eventually lead to an
      improvement in quality of test results and more accurate diagnosis. 

PMID- 24683416
TI  - Scientific Networks on Data Landscapes: Question Difficulty, Epistemic Success,
      and Convergence.
AB  - A scientific community can be modeled as a collection of epistemic agents
      attempting to answer questions, in part by communicating about their hypotheses
      and results. We can treat the pathways of scientific communication as a network.
      When we do, it becomes clear that the interaction between the structure of the
      network and the nature of the question under investigation affects epistemic
      desiderata, including accuracy and speed to community consensus. Here we build on
      previous work, both our own and others', in order to get a firmer grasp on
      precisely which features of scientific communities interact with which features
      of scientific questions in order to influence epistemic outcomes. Here we
      introduce a measure on the landscape meant to capture some aspects of the
      difficulty of answering an empirical question. We then investigate both how
      different communication networks affect whether the community finds the best
      answer and the time it takes for the community to reach consensus on an answer.
      We measure these two epistemic desiderata on a continuum of networks sampled from
      the Watts-Strogatz spectrum. It turns out that finding the best answer and
      reaching consensus exhibit radically different patterns. The time it takes for a
      community to reach a consensus in these models roughly tracks mean path length in
      the network. Whether a scientific community finds the best answer, on the other
      hand, tracks neither mean path length nor clustering coefficient.

PMID- 24683417
TI  - Positive Psychotherapy for Smoking Cessation: Treatment Development, Feasibility
      and Preliminary Results.
AB  - Low positive and high negative affect predict low rates of smoking abstinence
      among smokers making a quit attempt. Positive Psychotherapy can both increase
      positive affect and decrease negative affect and therefore may be a useful
      adjunct to behavioral smoking counseling. The purpose of the present study was to
      assess the feasibility and acceptability of a Positive Psychotherapy for Smoking
      Cessation (PPT-S) intervention that integrates standard smoking cessation
      counseling with nicotine patch and a package of positive psychology
      interventions. We delivered PPT-S to 19 smokers who were low in positive affect
      at baseline. Rates of session attendance and satisfaction with treatment were
      high, and most participants reported using and benefiting from the positive
      psychology interventions. Almost one-third of participants (31.6%) sustained
      smoking abstinence for 6 months after their quit date. Future studies to assess
      the relative efficacy of PPT-S compared to standard smoking cessation treatment
      are warranted.

PMID- 24683419
TI  - "It's like you are just a spectator in this thing": Experiencing social life the
      'aspie' way.
AB  - This study explores the experiences of people with Asperger syndrome (AS) from a
      sociological perspective using the theoretical approaches of ethnomethodology and
      symbolic interactionism. In-depth interviews were conducted with 16 people with
      AS and three key themes of feeling different, trying to fit in and safe spaces
      are considered here. We suggest that people with AS develop a different symbolic
      capacity to most people and have difficulties in making sense of social
      encounters. While these difficulties can be overcome, to some degree, by
      developing strategies to try to fit in, this learning remains at a superficial
      level and is not internalised through the process of socialisation. Without being
      able to derive a firm sense of reality from spontaneous involvement in social
      encounters, participants feel "unruled, unreal and anomic" (Goffman, 1967: 135)
      and experience intense autistic emotion (Davidson, 2007a,b).

PMID- 24683418
TI  - Confronting, Representing, and Believing Counterintuitive Concepts: Navigating
      the Natural and the Supernatural.
AB  - Recent research shows that even preschoolers are skeptical; they frequently
      reject claims from other people when the claims conflict with their own
      perceptions and concepts. Yet, despite their skepticism, both children and adults
      come to believe in a variety of phenomena that defy their first-hand perceptions
      and intuitive conceptions of the world. In this review, we explore how children
      and adults acquire such concepts. We describe how a similar developmental process
      underlies mental representation of both the natural and the supernatural world,
      and we detail this process for two prominent supernatural counterintuitive ideas
      God and the afterlife. In doing so, we highlight the fact that conceptual
      development does not always move in the direction of greater empirical truth, as
      described within naturalistic domains. We consider factors that likely help
      overcome skepticism and, in doing so, promote belief in counterintuitive
      phenomena. These factors include qualities of the learners, aspects of the
      context, qualities of the informants, and qualities of the information. 

PMID- 24683420
TI  - The relative contributions of the abdominal visceral  and subcutaneous fat depots
      to cardiometabolic risk  in youth.
AB  - The aim of this study was to evaluate the association of abdominal visceral and
      subcutaneous fat, independent of total body fat, with cardiometabolic risk
      factors and insulin resistance among youth. Visceral and subcutaneous fat,
      percentage total body fat, insulin resistance (adjusted for lean body mass:
      Mlbm), blood pressure, glucose, insulin and lipids were obtained in 472 youth
      ages 6-18 years. Linear regression, adjusted for age, sex, race, Tanner stage and
      percentage total body fat, was used to evaluate associations of visceral and
      subcutaneous fat with cardiometabolic risk factors. Visceral fat was associated
      inversely with Mlbm (P = 0.003) and positively with fasting insulin (P = 0.002)
      and triglycerides (P = 0.002). Visceral fat levels above the mean were associated
      inversely with high-density lipoprotein (HDL) cholesterol (P = 0.002), and
      positively with systolic blood pressure (P < 0.0001) and non-HDL cholesterol (P <
      0.0001). Subcutaneous fat was associated inversely with Mlbm (P = 0.003) and HDL
      cholesterol (P < 0.05), and positively with fasting glucose (P < 0.05), fasting
      insulin (P = 0.0003), systolic blood pressure (P = 0.005) and triglycerides (P =
      0.003). Subcutaneous fat levels above the mean were associated with non-HDL
      cholesterol (P = 0.0002). These findings suggest that there may be a threshold
      level of visceral and subcutaneous fat (regardless of total body fat), that when
      exceeded in childhood, is more likely to be associated with many cardiometabolic
      risk factors. Triglycerides and insulin resistance appear to be associated with
      these fat depots at even lower thresholds of abdominal adiposity.

PMID- 24683421
TI  - Facile Functionalization of Ag@SiO2 Core-Shell Metal Enhanced Fluorescence
      Nanoparticles for Cell Labeling.
AB  - We describe a versatile approach for functionalizing core-shell Ag@SiO2
      nanoparticles for live-cell imaging. The approach uses physical adsorption and
      does not need covalent linkage to synthesize antibody-based labels. The surface
      orientation is not controlled in this approach, but the signal enhancement is
      strong and consistent. Antibodies were then attached using a non-covalent process
      that takes advantage of biotin-avidin affinity. Metal-enhanced nanoparticles
      doped with rhodamine B were used as the luminescent reporter. The enhancement of
      rhodamine B was between 2.7-6.8 times. We demonstrated labeling of CD19+ Ramos B
      lymphocytes and CD4+ HuT 78 T lymphocytes using anti-CD19 and anti-CD4
      nanocomposite labels, respectively. This physical adsorption process can
      accommodate a variety of fluorophore types, and has broad potential in
      bioanalytical and biosensing applications.

PMID- 24683422
TI  - Using DelPhi capabilities to mimic protein's conformational reorganization with
      amino acid specific dielectric constants.
AB  - Many molecular events are associated with small or large conformational changes
      occurring in the corresponding proteins. Modeling such changes is a challenge and
      requires significant amount of computing time. From point of view of
      electrostatics, these changes can be viewed as a reorganization of local charges
      and dipoles in response to the changes of the electrostatic field, if the cause
      is insertion or deletion of a charged amino acid. Here we report a large scale
      investigation of modeling the changes of the folding energy due to single
      mutations involving charged group. This allows the changes of the folding energy
      to be considered mostly electrostatics in origin and to be calculated with DelPhi
      assigning residue-specific value of the internal dielectric constant of protein.
      The predicted energy changes are benchmarked against experimentally measured
      changes of the folding energy on a set of 257 single mutations. The best fit
      between experimental values and predicted changes is used to find out the
      effective value of the internal dielectric constant for each type of amino acid.
      The predicted folding free energy changes with the optimal, amino acid specific,
      dielectric constants are within RMSD=0.86 kcal/mol from experimentally measured
      changes.

PMID- 24683423
TI  - In silico investigation of pH-dependence of prolactin and human growth hormone
      binding to human prolactin receptor.
AB  - Experimental data shows that the binding of human prolactin (hPRL) to human
      prolactin receptor (hPRLr-ECD) is strongly pH-dependent, while the binding of the
      same receptor to human growth hormone (hGH) is pH-independent. Here we carry in
      silico analysis of the molecular effects causing such a difference and reveal the
      role of individual amino acids. It is shown that the computational modeling
      correctly predicts experimentally determined pKa's of histidine residues in an
      unbound state in the majority of the cases and the pH-dependence of the binding
      free energy. Structural analysis carried in conjunction with calculated pH
      dependence of the binding revealed that the main reason for pH-dependence of the
      binding of hPRL-hPRLr-ECD is a number of salt- bridges across the interface of
      the complex, while no salt-bridges are formed in the hGH-hPRlr-ECD. Specifically,
      most of the salt-bridges involve histidine residues and this is the reason for
      the pH-dependence across a physiological range of pH. The analysis not only
      revealed the molecular mechanism of the pH-dependence of the hPRL-hPRLr-ECD, but
      also provided critical insight into the underlying physic-chemical mechanism.

PMID- 24683425
TI  - Method Issues in Epidemiological Studies of Medically Unexplained Symptom-based
      Conditions in Veterans.
AB  - Symptom-based conditions such as chronic fatigue syndrome (CFS) and medically
      unexplained multi-symptom illness (MSI) are fairly common in the general
      population and are also important veteran's health concerns due to their higher
      frequency among U.S. veterans who served during the 1990-1991 Gulf War. CFS, MSI,
      and other symptom-based conditions are often associated with considerable
      morbidity due to fatigue, chronic pain, neurologic symptoms, and other symptoms
      that can impair the quality of life. This article discusses several important
      issues of methodology that arise in population studies of CFS and MSI. These
      include the exclusion criteria that have been used in population studies to
      define CFS-like illness and unexplained MSI, the potential for false positive and
      false negative assessments of illness status, the potential for sex differences,
      and the poorly understood natural history of these symptom-based conditions
      across the life span. As an empirical example of these methodology issues, we
      examined existing data from a 2005 follow-up survey. We found that 64.9% (762 of
      1,175) of female Gulf War veterans and 53.4% (2,530 of 4,739) of male Gulf War
      veterans had 1 or more exclusionary medical conditions. The prevalence among
      veterans with one or more exclusionary medical conditions increased markedly by
      age among females and those with a low income.

PMID- 24683424
TI  - DelPhi Web Server: A comprehensive online suite for electrostatic calculations of
      biological macromolecules and their complexes.
AB  - Here we report a web server, the DelPhi web server, which utilizes DelPhi program
      to calculate electrostatic energies and the corresponding electrostatic potential
      and ionic distributions, and dielectric map. The server provides extra services
      to fix structural defects, as missing atoms in the structural file and allows for
      generation of missing hydrogen atoms. The hydrogen placement and the
      corresponding DelPhi calculations can be done with user selected force field
      parameters being either Charmm22, Amber98 or OPLS. Upon completion of the
      calculations, the user is given option to download fixed and protonated
      structural file, together with the parameter and Delphi output files for further
      analysis. Utilizing Jmol viewer, the user can see the corresponding structural
      file, to manipulate it and to change the presentation. In addition, if the
      potential map is requested to be calculated, the potential can be mapped onto the
      molecule surface. The DelPhi web server is available from
      http://compbio.clemson.edu/delphi_webserver.

PMID- 24683426
TI  - A brief scientific biography of Prof. Alan J. Hunt.

PMID- 24683427
TI  - Hydroxysteroid sulfotransferase 2B1b expression and localization in normal human
      brain.
AB  - Steroid sulfonation in the human brain has not been well characterized. The major
      sulfotransferase (SULT) isoforms that conjugate steroids in humans are SULT1E1,
      SULT2A1, and SULT2B1b. SULT2B1b catalyzes the sulfonation of 3beta
      hydroxysteroids, including neurosteroids dehydroepiandrosterone and pregnenolone,
      as well as cholesterol and several hydroxycholesterols. SULT2B1b mRNA and protein
      expression were detected in adult and fetal human brain sections, whereas neither
      mRNA, nor protein expression were identified for SULT1E1 or SULT2A1. Using
      immunohistochemical analysis, SULT2B1b expression was detected in neurons and
      oligodendrocytes in adult brain and in epithelial tissues in 28-week-old fetal
      brain. Sulfonation of cholesterol, oxysterols, and neurosteroids in the brain is
      apparently catalyzed by SULT2B1b since expression of neither SULT2A1 nor SULT1E1
      was detected in human brain sections. SULT2B1b mRNA and protein were also
      detected in human U373-MG glioblastoma cells. Both mRNA and protein expression of
      liver X receptor (LXR)-beta, but not LXR-alpha, were detected in U373-MG cells,
      and LXR-beta activation resulted in a decrease in SULT2B1b protein expression.
      Since hydroxycholesterols are important physiological LXR activators, this
      suggests a role for regulation of sterol metabolism by LXR and SULT2B1b.
      Therefore, elucidating key enzymes in the metabolism of cholesterol and
      neurosteroids could help define the properties of steroid conjugation in the
      human brain.

PMID- 24683429
TI  - Revision total hip arthroplasty combined with subtrochanteric shortening
      osteotomy: case report.
AB  - Revision surgery is one of the most difficult reconstructive challenges facing
      orthopaedic surgeons; therefore, many new techniques and implants are needed to
      ensure that such patient can be successfully treated. We report a 66-year old
      female with a chronic dislocated bipolar hip prosthesis. She underwent a revision
      total hip arthroplasty combined with V-shaped subtrochanteric shortening
      osteotomy. This report demonstrates that V-shaped subtrochanteric shortening
      osteotomy can be used for revision surgery. Nevertheless, this technique is not
      suitable for all hip revisions, and the indications and various possible
      procedures and devices should be carefully considered to select the best
      treatment for each patient. We believe that the current report provides evidence
      supporting a new technical option for complex cases during revision THA. 

PMID- 24683428
TI  - Cardiac fibroblast-derived 3D extracellular matrix seeded with mesenchymal stem
      cells as a novel device to transfer cells to the ischemic myocardium.
AB  - PURPOSE: Demonstrate a novel manufacturing method to generate extracellular
      matrix scaffolds from cardiac fibroblasts (CF-ECM) as a therapeutic mesenchymal
      stem cell-transfer device. MATERIALS AND METHODS: Rat CF were cultured at high
      density (~1.6*105/cm2) for 10-14 days. Cell sheets were removed from the culture
      dish by incubation with EDTA and decellularized with water and peracetic acid. CF
      ECM was characterized by mass spectrometry, immunofluorescence and scanning
      electron microscopy. CF-ECM seeded with human embryonic stem cell derived
      mesenchymal stromal cells (hEMSCs) were transferred into a mouse myocardial
      infarction model. 48 hours later, mouse hearts were excised and examined for CF
      ECM scaffold retention and cell transfer. RESULTS: CF-ECM scaffolds are composed
      of fibronectin (82%), collagens type I (13%), type III (3.4%), type V (0.2%),
      type II (0.1%) elastin (1.3%) and 18 non-structural bioactive molecules.
      Scaffolds remained intact on the mouse heart for 48 hours without the use of
      sutures or glue. Identified hEMSCs were distributed from the epicardium to the
      endocardium. CONCLUSIONS: High density cardiac fibroblast culture can be used to
      generate CF-ECM scaffolds. CF-ECM scaffolds seeded with hEMSCs can be maintained
      on the heart without suture or glue. hEMSC are successfully delivered throughout
      the myocardium.

PMID- 24683431
TI  - On Numerical Aspects of Bayesian Model Selection in High and Ultrahigh
      dimensional Settings.
AB  - This article examines the convergence properties of a Bayesian model selection
      procedure based on a non-local prior density in ultrahigh-dimensional settings.
      The performance of the model selection procedure is also compared to popular
      penalized likelihood methods. Coupling diagnostics are used to bound the total
      variation distance between iterates in an Markov chain Monte Carlo (MCMC)
      algorithm and the posterior distribution on the model space. In several
      simulation scenarios in which the number of observations exceeds 100, rapid
      convergence and high accuracy of the Bayesian procedure is demonstrated.
      Conversely, the coupling diagnostics are successful in diagnosing lack of
      convergence in several scenarios for which the number of observations is less
      than 100. The accuracy of the Bayesian model selection procedure in identifying
      high probability models is shown to be comparable to commonly used penalized
      likelihood methods, including extensions of smoothly clipped absolute deviations
      (SCAD) and least absolute shrinkage and selection operator (LASSO) procedures.

PMID- 24683430
TI  - The de-ubiquitinating enzyme ataxin-3 does not modulate disease progression in a
      knock-in mouse model of Huntington disease.
AB  - Ataxin-3 is a deubiquitinating enzyme (DUB) that participates in ubiquitin
      dependent protein quality control pathways and, based on studies in model
      systems, may be neuroprotective against toxic polyglutamine proteins such as the
      Huntington's disease (HD) protein, huntingtin (htt). HD is one of at least nine
      polyglutamine neurodegenerative diseases in which disease-causing proteins
      accumulate in ubiquitin-positive inclusions within neurons. In studies crossing
      mice null for ataxin-3 to an established HD knock-in mouse model (HdhQ200), we
      tested whether loss of ataxin-3 alters disease progression, perhaps by impairing
      the clearance of mutant htt or the ubiquitination of inclusions. While loss of
      ataxin-3 mildly exacerbated age-dependent motor deficits, it did not alter
      inclusion formation, ubiquitination of inclusions or levels of mutant or normal
      htt. Ataxin-3, itself a polyglutamine-containing protein with multiple ubiquitin
      binding domains, was not observed to localize to htt inclusions. Changes in
      neurotransmitter receptor binding known to occur in HD knock-in mice also were
      not altered by the loss of ataxin-3, although we unexpectedly observed increased
      GABAA receptor binding in the striatum of HdhQ200 mice, which has not previously
      been noted. Finally, we confirmed that CNS levels of hsp70 are decreased in HD
      mice as has been reported in other HD mouse models, regardless of the presence or
      absence of ataxin-3. We conclude that while ataxin-3 may participate in protein
      quality control pathways, it does not critically regulate the handling of mutant
      htt or contribute to major features of disease pathogenesis in HD. 

PMID- 24683432
TI  - How Gene Networks Can Uncover Novel CVD Players.
AB  - Cardiovascular diseases (CVD) are complex, involving numerous biological entities
      from genes and small molecules to organ function. Placing these entities in
      networks where the functional relationships among the constituents are drawn can
      aid in our understanding of disease onset, progression and prevention. While
      networks, or interactomes, are often classified by a general term, say lipids or
      inflammation, it is a more encompassing class of network that is more informative
      in showing connections among the active entities and allowing better hypotheses
      of novel CVD players to be formulated. A range of networks will be presented
      whereby the potential to bring new objects into the CVD milieu will be
      exemplified.

PMID- 24683433
TI  - Orientation Determination of Cryo-EM Images Using Least Unsquared Deviations.
AB  - A major challenge in single particle reconstruction from cryo-electron microscopy
      is to establish a reliable ab initio three-dimensional model using two
      dimensional projection images with unknown orientations. Common-lines-based
      methods estimate the orientations without additional geometric information.
      However, such methods fail when the detection rate of common-lines is too low due
      to the high level of noise in the images. An approximation to the least squares
      global self-consistency error was obtained in [A. Singer and Y. Shkolnisky, SIAM
      J. Imaging Sci., 4 (2011), pp. 543-572] using convex relaxation by semidefinite
      programming. In this paper we introduce a more robust global self-consistency
      error and show that the corresponding optimization problem can be solved via
      semidefinite relaxation. In order to prevent artificial clustering of the
      estimated viewing directions, we further introduce a spectral norm term that is
      added as a constraint or as a regularization term to the relaxed minimization
      problem. The resulting problems are solved using either the alternating direction
      method of multipliers or an iteratively reweighted least squares procedure.
      Numerical experiments with both simulated and real images demonstrate that the
      proposed methods significantly reduce the orientation estimation error when the
      detection rate of common-lines is low.

PMID- 24683434
TI  - Extending the Generalised Pareto Distribution for Novelty Detection in High
      Dimensional Spaces.
AB  - Novelty detection involves the construction of a "model of normality", and then
      classifies test data as being either "normal" or "abnormal" with respect to that
      model. For this reason, it is often termed one-class classification. The approach
      is suitable for cases in which examples of "normal" behaviour are commonly
      available, but in which cases of "abnormal" data are comparatively rare. When
      performing novelty detection, we are typically most interested in the tails of
      the normal model, because it is in these tails that a decision boundary between
      "normal" and "abnormal" areas of data space usually lies. Extreme value
      statistics provides an appropriate theoretical framework for modelling the tails
      of univariate (or low-dimensional) distributions, using the generalised Pareto
      distribution (GPD), which can be demonstrated to be the limiting distribution for
      data occurring within the tails of most practically-encountered probability
      distributions. This paper provides an extension of the GPD, allowing the
      modelling of probability distributions of arbitrarily high dimension, such as
      occurs when using complex, multimodel, multivariate distributions for performing
      novelty detection in most real-life cases. We demonstrate our extension to the
      GPD using examples from patient physiological monitoring, in which we have
      acquired data from hospital patients in large clinical studies of high-acuity
      wards, and in which we wish to determine "abnormal" patient data, such that early
      warning of patient physiological deterioration may be provided.

PMID- 24683435
TI  - The emerging role of TRalpha1 in cardiac repair: potential therapeutic
      implications.
AB  - Thyroid hormone (TH) is critical for adapting living organisms to environmental
      stress. Plasma circulating tri-iodothyronine (T3) levels drop in most disease
      states and are associated with increased oxidative stress. In this context, T3
      levels in plasma appear to be an independent determinant for the recovery of
      cardiac function after myocardial infarction in patients. Thyroid hormone
      receptor alpha1 (TRalpha1) seems to be crucial in this response; TRalpha1
      accumulates to cell nucleus upon activation of stress induced growth kinase
      signaling. Furthermore, overexpression of nuclear TRalpha1 in cardiomyocytes can
      result in pathological or physiological growth (dual action) in absence or
      presence of its ligand, respectively. Accordingly, inactivation of TRalpha1
      receptor prevents reactive hypertrophy after myocardial infarction and results in
      heart failure with increased phospholamban (PLB) expression and marked activation
      of p38MAPK. In line with this evidence, TH is shown to limit ischemia/reperfusion
      injury and convert pathologic to physiologic growth after myocardial infarction
      via TRalpha1 receptor. TRalpha1 receptor may prove to be a novel pharmacological
      target for cardiac repair/regeneration therapies.

PMID- 24683436
TI  - Oxidative stress and metabolic syndrome: cause or consequence of Alzheimer's
      disease?
AB  - Alzheimer's disease (AD) is a major neurodegenerative disease affecting the
      elderly. Clinically, it is characterized by a progressive loss of memory and
      cognitive function. Neuropathologically, it is characterized by the presence of
      extracellular beta-amyloid (Abeta) deposited as neuritic plaques (NP) and
      neurofibrillary tangles (NFT) made of abnormal and hyperphosphorylated tau
      protein. These lesions are capable of generating the neuronal damage that leads
      to cell death and cognitive failure through the generation of reactive oxygen
      species (ROS). Evidence indicates the critical role of Abeta metabolism in
      prompting the oxidative stress observed in AD patients. However, it has also been
      proposed that oxidative damage precedes the onset of clinical and pathological AD
      symptoms, including amyloid-beta deposition, neurofibrillary tangle formation,
      vascular malfunction, metabolic syndrome, and cognitive decline. This paper
      provides a brief description of the three main proteins associated with the
      development of the disease (Abeta, tau, and ApoE) and describes their role in the
      generation of oxidative stress. Finally, we describe the mitochondrial
      alterations that are generated by Abeta and examine the relationship of vascular
      damage which is a potential prognostic tool of metabolic syndrome. In addition,
      new therapeutic approaches targeting ROS sources and metabolic support were
      reported. 

PMID- 24683437
TI  - Amyloid beta: multiple mechanisms of toxicity and only some protective effects?
AB  - Amyloid beta (Abeta) is a peptide of 39-43 amino acids found in large amounts and
      forming deposits in the brain tissue of patients with Alzheimer's disease (AD).
      For this reason, it has been implicated in the pathophysiology of damage observed
      in this type of dementia. However, the role of Abeta in the pathophysiology of AD
      is not yet precisely understood. Abeta has been experimentally shown to have a
      wide range of toxic mechanisms in vivo and in vitro, such as excitotoxicity,
      mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis,
      oxidative stress, and so forth. In contrast, Abeta has also shown some
      interesting neuroprotective and physiological properties under certain
      experimental conditions, suggesting that both physiological and pathological
      roles of Abeta may depend on several factors. In this paper, we reviewed both
      toxic and protective mechanisms of Abeta to further explore what their potential
      roles could be in the pathophysiology of AD. The complete understanding of such
      apparently opposed effects will also be an important guide for the therapeutic
      efforts coming in the future.

PMID- 24683438
TI  - Anti-inflammatory effect of recreational exercise in TNBS-induced colitis in
      rats: role of NOS/HO/MPO system.
AB  - There are opposite views in the available literature: Whether physical exercise
      has a protective effect or not on the onset of inflammatory bowel disease (IBD).
      Therefore, we investigated the effects of recreational physical exercise before
      the induction of colitis. After 6 weeks of voluntary physical activity (running
      wheel), male Wistar rats were treated with TNBS (10 mg). 72 hrs after
      trinitrobenzene sulphonic acid (TNBS) challenge we measured colonic gene (TNF
      alpha, IL-1beta, CXCL1 and IL-10) and protein (TNF-alpha) expressions of various
      inflammatory mediators and enzyme activities of heme oxygenase (HO), nitric oxide
      synthase (NOS), and myeloperoxidase (MPO) enzymes. Wheel running significantly
      increased the activities of HO, constitutive NOS (cNOS) isoform. Furthermore, 6
      weeks of running significantly decreased TNBS-induced inflammatory markers,
      including extent of lesions, severity of mucosal damage, and gene expression of
      IL-1beta, CXCL1, and MPO activity, while IL-10 gene expression and cNOS activity
      were increased. iNOS activity decreased and the activity of HO enzyme increased,
      but not significantly, compared to the sedentary TNBS-treated group. In
      conclusion, recreational physical exercise can play an anti-inflammatory role by
      downregulating the gene expression of proinflammatory mediators, inducing anti
      inflammatory mediators, and modulating the activities of HO and NOS enzymes in a
      rat model of colitis.

PMID- 24683440
TI  - Use of sentinel lymph node biopsy to select patients for local-regional therapy
      after neoadjuvant chemotherapy.
AB  - Use of sentinel lymph node biopsy for axillary staging of patients with breast
      cancer treated with neoadjuvant chemotherapy has been widely debated. Questions
      arise regarding the accuracy of sentinel lymph node biopsy in axillary staging
      for these patients and its use to determine further local-regional therapy,
      including surgery and radiation therapy. For patients who are clinically node
      negative at presentation, sentinel lymph node biopsy enables accurate staging of
      the axilla after neoadjuvant chemotherapy, and determination of which patients
      should go on to further axillary surgery and regional nodal radiation therapy.
      Importantly, performing axillary staging after completion of chemotherapy, rather
      than before chemotherapy, enables assessment of response to chemotherapy and the
      extent of residual disease. This information can assist the planning of adjuvant
      treatment. Recent data indicate that sentinel node biopsy can also be used to
      assess disease response after neoadjuvant chemotherapy for patients with clinical
      N1 disease at presentation.

PMID- 24683439
TI  - Effects of downregulation of microRNA-181a on H2O2-induced H9c2 cell apoptosis
      via the mitochondrial apoptotic pathway.
AB  - Glutathione peroxidase-1 (GPx1) is a pivotal intracellular antioxidant enzyme
      that enzymatically reduces hydrogen peroxide to water to limit its harmful
      effects. This study aims to identify a microRNA (miRNA) that targets GPx1 to
      maintain redox homeostasis. Dual luciferase assays combined with mutational
      analysis and immunoblotting were used to validate the bioinformatically predicted
      miRNAs. We sought to select miRNAs that were responsive to oxidative stress
      induced by hydrogen peroxide (H2O2) in the H9c2 rat cardiomyocyte cell line.
      Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-181a in
      H2O2-treated H9c2 cells was markedly upregulated. The downregulation of miR-181a
      significantly inhibited H2O2-induced cellular apoptosis, ROS production, the
      increase in malondialdehyde (MDA) levels, the disruption of mitochondrial
      structure, and the activation of key signaling proteins in the mitochondrial
      apoptotic pathway. Our results suggest that miR-181a plays an important role in
      regulating the mitochondrial apoptotic pathway in cardiomyocytes challenged with
      oxidative stress. MiR-181a may represent a potential therapeutic target for the
      treatment of oxidative stress-associated cardiovascular diseases. 

PMID- 24683441
TI  - A Quantitative Process for Enhancing End of Phase 2 Decisions.
AB  - The objectives of the phase 2 stage in a drug development program are to evaluate
      the safety and tolerability of different doses, select a promising dose range,
      and look for early signs of activity. At the end of phase 2, a decision to
      initiate phase 3 studies is made that involves the commitment of considerable
      resources. This multifactorial decision, generally made by balancing the current
      condition of a development organization's portfolio, the future cost of
      development, the competitive landscape, and the expected safety and efficacy
      benefits of a new therapy, needs to be a good one. In this article, we present a
      practical quantitative process that has been implemented for drugs entering phase
      2 at Amgen Ltd. to ensure a consistent and explicit evidence-based approach is
      used to contribute to decisions for new drug candidates. Broadly following this
      process will also help statisticians increase their strategic influence in drug
      development programs. The process is illustrated using an example from the
      pancreatic cancer indication. Embedded within the process is a predominantly
      Bayesian approach to predicting the probability of efficacy success in a future
      (frequentist) phase 3 program.

PMID- 24683443
TI  - Electronic health records access during a disaster.
AB  - As has been demonstrated previously, medical care providers that employ an
      electronic health records (EHR) system provide more appropriate, cost effective
      care. Those providers are also better positioned than those who rely on paper
      records to recover if their facility is damaged as a result of severe storms,
      fires, or other events. The events surrounding Superstorm Sandy in 2012 made it
      apparent that, with relatively little additional effort and investment, health
      care providers with EHR systems may be able to use those systems for patient care
      purposes even during disasters that result in damage to buildings and facilities,
      widespread power outages, or both. 

PMID- 24683444
TI  - Artificial control maturation of porcine oocyte by dibutyryl cyclicAMP.
AB  - In this study, we investigated the effects of various durations of dibutyryl
      cyclic AMP (dbcAMP) treatment on the in vitro maturation (IVM) and subsequent
      development of parthenogenetically activated embryos. Immature porcine oocytes
      were cultured with or without 1 mM dbcAMP during the first 20, 28, or 36 h of
      culture, and then incubated for an additional 24 h without dbcAMP. The expression
      of Wee1B, Myt, and Cdc25B and the level of maturation promoting factor (MPF) in
      metaphase II oocytes were analyzed by real-time PCR (qRT-PCR) and enzyme linked
      immunosorbent assay (ELISA), respectively. The distribution of actin
      microfilaments in oocytes was also assessed. Subsequently, apoptotic cells in
      blastocysts from each group were visualized by transferase-mediated dUTP nick-end
      labeling staining. Results showed that oocytes extruded the first polar body
      between 12 and 18 h after being released from dbcAMP. MPF activity in oocytes at
      28 + 24 h and 36 + 24 h after dbcAMP treatment was higher than that in the
      control group. Significantly more blastocysts were present among embryos in 28 +
      24 h (54.28% vs. 39.11%, P < 0.05) and 36 + 24 h (47.24% vs. 32.94%, P < 0.05)
      groups than among embryos cultured in the absence of dbcAMP. However, the number
      of total and apoptotic cells was not significantly different between groups. The
      distribution of actin microfilaments was abnormal in oocytes cultured for 60 h
      without dbcAMP. In addition, the expression of Wee1B, Myt, and Cdc25B was higher
      in the control group at 44 h than in the dbcAMP group, but there were no
      differences in expression at the other time points. In conclusion, dbcAMP
      treatment delays oocyte maturation and maintains oocyte quality.

PMID- 24683442
TI  - Mobile medical and health apps: state of the art, concerns, regulatory control
      and certification.
AB  - This paper examines the state of the art in mobile clinical and health-related
      apps. A 2012 estimate puts the number of health-related apps at no fewer than
      40,000, as healthcare professionals and consumers continue to express concerns
      about the quality of many apps, calling for some form of app regulatory control
      or certification to be put in place. We describe the range of apps on offer as of
      2013, and then present a brief survey of evaluation studies of medical and health
      related apps that have been conducted to date, covering a range of clinical
      disciplines and topics. Our survey includes studies that highlighted risks,
      negative issues and worrying deficiencies in existing apps. We discuss the
      concept of 'apps as a medical device' and the relevant regulatory controls that
      apply in USA and Europe, offering examples of apps that have been formally
      approved using these mechanisms. We describe the online Health Apps Library run
      by the National Health Service in England and the calls for a vetted medical and
      health app store. We discuss the ingredients for successful apps beyond the
      rather narrow definition of 'apps as a medical device'. These ingredients cover
      app content quality, usability, the need to match apps to consumers' general and
      health literacy levels, device connectivity standards (for apps that connect to
      glucometers, blood pressure monitors, etc.), as well as app security and user
      privacy. 'Happtique Health App Certification Program' (HACP), a voluntary app
      certification scheme, successfully captures most of these desiderata, but is
      solely focused on apps targeting the US market. HACP, while very welcome, is in
      ways reminiscent of the early days of the Web, when many "similar" quality
      benchmarking tools and codes of conduct for information publishers were proposed
      to appraise and rate online medical and health information. It is probably
      impossible to rate and police every app on offer today, much like in those early
      days of the Web, when people quickly realised the same regarding informational
      Web pages. The best first line of defence was, is, and will always be to educate
      consumers regarding the potentially harmful content of (some) apps. 

PMID- 24683445
TI  - Exosomes provide a protective and enriched source of miRNA for biomarker
      profiling compared to intracellular and cell-free blood.
AB  - INTRODUCTION: microRNA (miRNA) are small non-coding RNA species that are
      transcriptionally processed in the host cell and released extracellularly into
      the bloodstream. Normally involved in post-transcriptional gene silencing, the
      deregulation of miRNA has been shown to influence pathogenesis of a number of
      diseases. BACKGROUND: Next-generation deep sequencing (NGS) has provided the
      ability to profile miRNA in biological fluids making this approach a viable
      screening tool to detect miRNA biomarkers. However, collection and handling
      procedures of blood needs to be greatly improved for miRNA analysis in order to
      reliably detect differences between healthy and disease patients. Furthermore,
      ribonucleases present in blood can degrade RNA upon collection rendering
      extracellular miRNA at risk of degradation. These factors have consequently
      decreased sensitivity and specificity of miRNA biomarker assays. METHODS: Here,
      we use NGS to profile miRNA in various blood components and identify differences
      in profiles within peripheral blood compared to cell-free plasma or serum and
      extracellular vesicles known as exosomes. We also analyse and compare the miRNA
      content in exosomes prepared by ultracentrifugation methods and commercial
      exosome isolation kits including treating samples with RNaseA. CONCLUSION: This
      study demonstrates that exosomal RNA is protected by RNaseA treatment and that
      exosomes provide a consistent source of miRNA for disease biomarker detection.

PMID- 24683446
TI  - Birth size and adult size in same-sex siblings discordant for fetal growth in the
      Early Determinants of Adult Health study.
AB  - Many studies have reported on relations between birth size and adult size but the
      findings to date are hard to compare due to the lack of uniform measures across
      studies. Interpretation of findings is also hampered by potential confounding by
      ethnic, socioeconomic and family factors. The purpose of this study is to explore
      these relationships in a comprehensive fashion, with multiple measures of birth
      size and adult size, using same-sex sibling controls discordant in birth weight
      to address potential confounding at the family level. Study subjects include
      pregnant women enrolled during 1959-1966 in the Child Health and Development
      Study in Oakland, CA and the Boston, MA, and providence, RI, sites of the
      Collaborative Perinatal Project in New England, currently combined into the New
      England Family Study. We assessed 392 offspring (mean age 43 years), the great
      majority as sibships as available. Our analyses confirm the positive association
      between birth weight and adult length reported in other studies, with a change in
      adult height of 1.25 cm (95% CI: 0.79 to 1.70 cm) for each quintile change in
      standardized birth weight. No associations were seen between birth weight and
      adult fatness for which findings in other studies are highly variable. As adult
      weight is likely to reflect recent variations in the adult nutritional
      environment rather than the early environment, it may be more useful for studies
      of birth size and adult size to focus on adult length rather than weight measures
      in evaluating the role of early influences on adult health. 

PMID- 24683448
TI  - Aligning oral mesalazine treatment to health service priorities: guidance for
      nurses.
AB  - Oral mesalazine represents a crucial front-line agent for the treatment of active
      ulcerative colitis (UC) and the maintenance of remission. Clinical aspects of
      mesalazine therapy are guided by robust evidence-based guidelines, although there
      is a relative paucity of guidance examining the specific administrative and
      professional issues faced by inflammatory bowel disease (IBD) nurses. As IBD
      nurses frequently influence treatment decisions in UC, this article was written
      to provide a practical review of the key evidence and issues affecting mesalazine
      treatment. Therefore, it may act as an additional resource for IBD nurses, to
      enhance prescribing decisions. Using the UK's Quality, Innovation, Productivity
      and Prevention (QIPP) agenda as a framework, it considers clinical and health
      service priorities affecting treatment decisions. The quality of care perspective
      naturally focuses on efficacy; recent interest in specific aspects of efficacy,
      such as the speed of symptom resolution allows targeting of mesalazine treatment
      to individual needs. Furthermore, innovative adherence programmes build on the
      latest evidence to develop robust, integrated patient support approaches. In
      terms of productivity, nurse-led activities and more sophisticated management
      strategies may offer the best routes towards reducing the costs of care. Key
      opportunities for preventing ill health include improving adherence to
      maintenance therapy and achieving mucosal healing. The principles and approaches
      highlighted by the QIPP agenda emphasise that prescribing decisions for
      mesalazine in UC must take account of the full spectrum of clinical and health
      service needs, and cannot focus on any one element in isolation.

PMID- 24683447
TI  - Hepatitis B in pregnancy.
AB  - OBJECTIVE: Vertical transmission of the hepatitis B virus (HBV) is the commonest
      mode of infection and can be prevented with immunoprophylaxis of the infant and
      antiviral therapy in the mother. Our aim was to review a cohort of subjects with
      HBV in pregnancy to determine the prevalence of active disease or high HBV-DNA
      levels that required treatment to prevent transmission, and to review the
      management of mothers and infants. METHODS: A retrospective case-note review was
      conducted of all the HBV-infected pregnant women and their infants who attended
      the Newcastle obstetric services from 2007 to 2011. RESULTS: There were 113
      pregnancies in 81 women (median age 28 years; 15% hepatitis B e antigen (HBeAg)
      positive) during 2007-11. 71% of mothers were first diagnosed with HBV during
      pregnancy. The mothers were born in 28 different countries. 69% of mothers had an
      HBV-DNA level less than 2000 IU/mL and 13% had HBV-DNA levels greater than
      1.0*107 IU/mL so would be eligible for antiviral therapy to prevent transmission
      to the infant. 9% had active eAg-positive HBV and 3% had active eAg-negative HBV
      requiring treatment. All infants born to HBeAg-positive mothers received
      hepatitis B immunoglobulin (HBIG) appropriately and 76% of infants received a
      full HBV vaccination course. One infant born to an HBeAg-negative mother was
      hepatitis B surface antigen positive 1 year post-delivery. CONCLUSIONS: One in
      six women had active HBV requiring treatment or high HBV-DNA levels that would
      benefit from antiviral treatment to reduce the transmission risk. HBIG was
      administered appropriately but completion of the vaccination course was
      suboptimal.

PMID- 24683449
TI  - Enantioselective synthesis of hindered cyclic dialkyl ethers via catalytic oxa
      Michael/Michael desymmetrization.
AB  - An asymmetric oxa-Michael/Michael cascade reaction of p-quinols and alpha,beta
      unsaturated aldehydes provides access to hindered dialkyl ethers. A highly
      enantioselective oxa-Michael addition of a tertiary alcohol precedes an
      intramolecular cyclohexadienone desymmetrization, which allows for the
      concomitant formation of four contiguous stereocenters in a single step. The
      highly functionalized bicyclic frameworks are rapidly obtained from simple
      starting materials with good diastereoselection and serve as valuable precursors
      for further manipulation.

PMID- 24683450
TI  - A peptide-free, liposome-based oligosaccharide vaccine, adjuvanted with a natural
      killer T cell antigen, generates robust antibody responses in vivo.
AB  - Due to the prevalence of oligo- and polysaccharides on the surfaces of pathogenic
      organisms, carbohydrates are primary targets for recognition by antibodies
      generated by the immune systems of higher organisms. Consequently, substantial
      effort has been expended in efforts to develop vaccines based on carbohydrate
      epitopes. Typical approaches involve multivalent presentation of carbohydrate
      targets on antigenic peptides or proteins, which often involve substantial
      synthetic commitments and/or vaccines that are heterogeneous and difficult to
      characterize. We have developed a simple, liposome-based approach to generate
      multivalent carbohydrate vaccines, and in place of an antigenic peptide or
      protein, we have used a potent antigen for natural killer T cells. This vaccine,
      based on the Streptococcus pneumoniae serotype 14 polysaccharide, gave a response
      superior to that from a clinically used vaccine (Prevnar). The dependence of this
      response on liposome formation was demonstrated by comparison to a simple mixture
      of the oligosaccharide and the natural killer T cell adjuvant. The importance of
      the strength of the adjuvant was observed by use of a potent synthetic adjuvant
      and a weaker, bacterial derived glycolipid adjuvant. These results demonstrate
      the effectiveness of this novel and relatively simple means of generating
      carbohydrate-based vaccines.

PMID- 24683451
TI  - Life history mediates mate limitation and population viability in self
      incompatible plant species.
AB  - Genetically controlled self-incompatibility systems represent links between
      genetic diversity and plant demography with the potential to directly impact on
      population dynamics. We use an individual-based spatial simulation to investigate
      the demographic and genetic consequences of different self-incompatibility
      systems for plants that vary in reproductive capacity and lifespan. The results
      support the idea that, in the absence of inbreeding effects, populations of self
      incompatible species will often be smaller and less viable than self-compatible
      species, particularly for shorter-lived organisms or where potential fecundity is
      low. At high ovule production and low mortality, self-incompatible and self
      compatible species are demographically similar, thus self-incompatibility does
      not automatically lead to reduced mate availability or population viability.
      Overall, sporophytic codominant self-incompatibility was more limiting than
      gametophytic or sporophytic dominant systems, which generally behaved in a
      similar fashion. Under a narrow range of conditions, the sporophytic dominant
      system maintained marginally greater mate availability owing to the production of
      S locus homozygotes. While self-incompatibility reduces population size and
      persistence for a broad range of conditions, the actual number of S alleles,
      beyond that required for reproduction, is important for only a subset of life
      histories. For these situations, results suggest that addition of new S alleles
      may result in significant demographic rescue. 

PMID- 24683452
TI  - Extraordinary MHC class II B diversity in a non-passerine, wild bird: the
      Eurasian Coot Fulica atra (Aves: Rallidae).
AB  - The major histocompatibility complex (MHC) hosts the most polymorphic genes ever
      described in vertebrates. The MHC triggers the adaptive branch of the immune
      response, and its extraordinary variability is considered an evolutionary
      consequence of pathogen pressure. The last few years have witnessed the
      characterization of the MHC multigene family in a large diversity of bird
      species, unraveling important differences in its polymorphism, complexity, and
      evolution. Here, we characterize the first MHC class II B sequences isolated from
      a Rallidae species, the Eurasian Coot Fulica atra. A next-generation sequencing
      approach revealed up to 265 alleles that translated into 251 different amino acid
      sequences (beta chain, exon 2) in 902 individuals. Bayesian inference identified
      up to 19 codons within the presumptive peptide-binding region showing pervasive
      evidence of positive, diversifying selection. Our analyses also detected a
      significant excess of high-frequency segregating sites (average Tajima's D =
      2.36, P < 0.05), indicative of balancing selection. We found one to six different
      alleles per individual, consistent with the occurrence of at least three MHC
      class II B gene duplicates. However, the genotypes comprised of three alleles
      were by far the most abundant in the population investigated (49.4%), followed by
      those with two (29.6%) and four (17.5%) alleles. We suggest that these
      proportions are in agreement with the segregation of MHC haplotypes differing in
      gene copy number. The most widespread segregating haplotypes, according to our
      findings, would contain one single gene or two genes. The MHC class II of the
      Eurasian Coot is a valuable system to investigate the evolutionary implications
      of gene copy variation and extensive variability, the greatest ever found, to the
      best of our knowledge, in a wild population of a non-passerine bird. 

PMID- 24683453
TI  - Habitat type and ambient temperature contribute to bill morphology.
AB  - Avian bills are iconic structures for the study of ecology and evolution, with
      hypotheses about the morphological structure of bills dating back to Darwin.
      Several ecological and physiological hypotheses have been developed to explain
      the evolution of the morphology of bill shape. Here, we test some of these
      hypotheses such as the role of habitat, ambient temperature, body size,
      intraspecific competition, and ecological release on the evolution of bill
      morphology. Bill morphology and tarsus length were measured from museum specimens
      of yellow warblers, and grouped by habitat type, sex, and subspecies. We
      calculated the mean maximum daily temperature for the month of July, the hottest
      month for breeding specimens at each collecting location. Analysis of covariance
      models predicted total bill surface area as a function of sex, habitat type, body
      size, and temperature, and model selection techniques were used to select the
      best model. Habitat, mangrove forests compared with inland habitats, and climate
      had the largest effects on bill size. Coastal wetland habitats and island
      populations of yellow warblers had similar bill morphology, both of which are
      larger than mainland inland populations. Temperate but not tropical subspecies
      exhibited sexual dimorphism in bill morphology. Overall, this study provides
      evidence that multiple environmental factors, such as temperature and habitat,
      contribute to the evolution of bill morphology. 

PMID- 24683454
TI  - Predicting leaf traits of herbaceous species from their spectral characteristics.
AB  - Trait predictions from leaf spectral properties are mainly applied to tree
      species, while herbaceous systems received little attention in this topic.
      Whether similar trait-spectrum relations can be derived for herbaceous plants
      that differ strongly in growing strategy and environmental constraints is
      therefore unknown. We used partial least squares regression to relate key traits
      to leaf spectra (reflectance, transmittance, and absorbance) for 35 herbaceous
      species, sampled from a wide range of environmental conditions. Specific Leaf
      Area and nutrient-related traits (N and P content) were poorly predicted from any
      spectrum, although N prediction improved when expressed on a per area basis
      (mg/m(2) leaf surface) instead of mass basis (mg/g dry matter). Leaf dry matter
      content was moderately to good correlated with spectra. We explain our results by
      the range of environmental constraints encountered by herbaceous species; both N
      and P limitations as well as a range of light and water availabilities occurred.
      This weakened the relation between the measured response traits and the leaf
      constituents that are truly responsible for leaf spectral behavior. Indeed, N
      predictions improve considering solely upper or under canopy species. Therefore,
      trait predictions in herbaceous systems should focus on traits relating to dry
      matter content and the true, underlying drivers of spectral properties. 

PMID- 24683455
TI  - A bird distribution model for ring recovery data: where do the European robins
      go?
AB  - For the study of migratory connectivity, birds have been individually marked by
      metal rings for more than 100 years. The resulting ring recovery data have been
      compiled in numerous bird migration atlases. However, estimation of what
      proportion of a particular population is migrating to which region is confounded
      by spatial heterogeneity in ring recovery probability. We present a product
      multinomial model that enables quantifying the continent-wide distribution of
      different bird populations during different seasons based on ring recovery data
      while accounting for spatial heterogeneity of ring recovery probability. We
      applied the model to an example data set of the European robin Erithacus
      rubecula. We assumed that ring recovery probability was equal between different
      groups of birds and that survival probability was constant. Simulated data
      indicate that violation of the assumption of constant survival did not affect our
      estimated bird distribution parameters but biased the estimates for recovery
      probability. Posterior predictive model checking indicated a good general model
      fit but also revealed lack of fit for a few groups of birds. This lack of fit may
      be due to between-group differences in the spatial distribution on smaller scales
      within regions. We found that 48% of the Scandinavian robins, but only 31% of the
      central European robins, wintered in northern Africa. The remaining parts of both
      populations wintered in southern and central Europe. Therefore, a substantial
      part of the Scandinavian population appears to leap over individuals from the
      central European population during migration. The model is applied to summary
      tables of numbers of ringed and recovered birds. This allows us to handle very
      large data sets as, for example, those presented in bird migration atlases. 

PMID- 24683456
TI  - The effects of insects, nutrients, and plant invasion on community structure and
      function above-and belowground.
AB  - Soil nutrient availability, invasive plants, and insect presence can directly
      alter ecosystem structure and function, but less is known about how these factors
      may interact. In this 6-year study in an old-field ecosystem, we manipulated
      insect abundance (reduced and control), the propagule pressure of an invasive
      nitrogen-fixing plant (propagules added and control), and soil nutrient
      availability (nitrogen added, nitrogen reduced and control) in a fully crossed,
      completely randomized plot design. We found that nutrient amendment and,
      occasionally, insect abundance interacted with the propagule pressure of an
      invasive plant to alter above-and belowground structure and function at our site.
      Not surprisingly, nutrient amendment had a direct effect on aboveground biomass
      and soil nutrient mineralization. The introduction of invasive nitrogen-fixing
      plant propagules interacted with nutrient amendment and insect presence to alter
      soil bacterial abundance and the activity of the microbial community. While the
      larger-scale, longer-term bulk measurements such as biomass production and
      nutrient mineralization responded to the direct effects of our treatments, the
      shorter-term and dynamic microbial communities tended to respond to interactions
      among our treatments. Our results indicate that soil nutrients, invasive plants,
      and insect herbivores determine both above-and belowground responses, but whether
      such effects are independent versus interdependent varies with scale. 

PMID- 24683457
TI  - Determining population structure and hybridization for two iris species.
AB  - Identifying processes that promote or limit gene flow can help define the
      ecological and evolutionary history of a species. Furthermore, defining those
      factors that make up "species boundaries" can provide a definition of the
      independent evolutionary trajectories of related taxa. For many species, the
      historic processes that account for their distribution of genetic variation
      remain unresolved. In this study, we examine the geographic distribution of
      genetic diversity for two species of Louisiana Irises, Iris brevicaulis and Iris
      fulva. Specifically, we asked how populations are structured and if population
      structure coincides with potential barriers to gene flow. We also asked whether
      there is evidence of hybridization between these two species outside Louisiana
      hybrid zones. We used a genotyping-by-sequencing approach and sampled a large
      number of single nucleotide polymorphisms across these species' genomes. Two
      different population assignment methods were used to resolve population structure
      in I. brevicaulis; however, there was considerably less population structure in
      I. fulva. We used a species tree approach to infer phylogenies both within and
      between populations and species. For I. brevicaulis, the geography of the
      collection locality was reflected in the phylogeny. The I. fulva phylogeny
      reflected much less structure than detected for I. brevicaulis. Lastly, combining
      both species into a phylogenetic analysis resolved two of six populations of I.
      brevicaulis that shared alleles with I. fulva. Taken together, our results
      suggest major differences in the level and pattern of connectivity among
      populations of these two Louisiana Iris species. 

PMID- 24683459
TI  - Disturbance by large herbivores alters the relative importance of the ecological
      processes that influence the assembly pattern in heterogeneous meta-communities.
AB  - Disturbance caused by large herbivores can affect the relative importance of
      ecological processes in determining community assembly and may cause a systematic
      loss of biodiversity across scales. To examine changes in the community assembly
      pattern caused by an overabundance of large herbivores in Japan, we analyzed
      community composition data from before and after the overabundance occurred. The
      community assembly pattern becomes more random after the deer overabundance. In
      addition, result of variation partitioning revealed decrease in importance of
      environmental processes and increase in importance of spatial processes. However,
      response of turnover rate, niche breadth, and niche overlap was heterogeneous,
      according to scale of each environmental gradient. Our results emphasize the
      importance of conserving habitat specialists that represent the local environment
      (habitat type and topography) at various altitudinal ranges to maintain
      biodiversity at regional scales under the increasing pressure of large
      herbivores. 

PMID- 24683458
TI  - Equal nonbreeding period survival in adults and juveniles of a long-distant
      migrant bird.
AB  - In migrant birds, survival estimates for the different life-history stages
      between fledging and first breeding are scarce. First-year survival is shown to
      be strongly reduced compared with annual survival of adult birds. However, it
      remains unclear whether the main bottleneck in juvenile long-distant migrants
      occurs in the postfledging period within the breeding ranges or en route.
      Quantifying survival rates during different life-history stages and during
      different periods of the migration cycle is crucial to understand forces driving
      the evolution of optimal life histories in migrant birds. Here, we estimate
      survival rates of adult and juvenile barn swallows (Hirundo rusticaL.) in the
      breeding and nonbreeding areas using a population model integrating survival
      estimates in the breeding ranges based on a large radio-telemetry data set and
      published estimates of demographic parameters from large-scale population
      monitoring projects across Switzerland. Input parameters included the country
      wide population trend, annual productivity estimates of the double-brooded
      species, and year-to-year survival corrected for breeding dispersal. Juvenile
      survival in the 3-week postfledging period was low (S = 0.32; SE = 0.05), whereas
      in the rest of the annual cycle survival estimates of adults and juveniles were
      similarly high (S > 0.957). Thus, the postfledging period was the main survival
      bottleneck, revealing the striking result that nonbreeding period mortality
      (including migration) is not higher for juveniles than for adult birds.
      Therefore, focusing future research on sources of variation in postfledging
      mortality can provide new insights into determinants of population dynamics and
      life-history evolution of migrant birds. 

PMID- 24683460
TI  - Resource defense and monopolization in a marked population of ruby-throated
      hummingbirds (Archilochus colubris).
AB  - Resource defense behavior is often explained by the spatial and temporal
      distribution of resources. However, factors such as competition, habitat
      complexity, and individual space use may also affect the capacity of individuals
      to defend and monopolize resources. Yet, studies frequently focus on one or two
      factors, overlooking the complexity found in natural settings. Here, we addressed
      defense and monopolization of nectar feeders in a population of free-ranging ruby
      throated hummingbirds marked with passive integrated transponder (PIT tags). Our
      study system consisted of a 44 ha systematic grid of 45 feeders equipped with PIT
      tag detectors recording every visit made at feeders. We modeled the number of
      visits by competitors (NVC) at feeders in response to space use by a focal
      individual potentially defending a feeder, number of competitors, nectar sucrose
      concentration, and habitat visibility. Individuals who were more concentrated at
      certain feeders on a given day and who were more stable in their use of the grid
      throughout the season gained higher exclusivity in the use of those feeders on
      that day, especially for males competing against males. The level of spatial
      concentration at feeders and its negative effect on NVC was, however, highly
      variable among individuals, suggesting a continuum in resource defense
      strategies. Although the apparent capacity to defend feeders was not affected by
      competition or nectar sucrose concentration, the level of monopolization
      decreased with increasing number of competitors and higher nectar quality.
      Defense was enhanced by visibility near feeders, but only in forested habitats.
      The reverse effect of visibility in open habitats was more difficult to interpret
      as it was probably confounded by perch availability, from which a bird can defend
      its feeder. Our study is among the first to quantify the joint use of food
      resource by overlapping individuals unconstrained in their use of space. Our
      results show the importance of accounting for variation in space use among
      individuals as it translated into varying levels of defense and monopolization of
      feeders regardless of food resource distribution. 

PMID- 24683461
TI  - Grassland invaders and their mycorrhizal symbionts: a study across climate and
      invasion gradients.
AB  - Controlled experiments show that arbuscular mycorrhizal fungi (AMF) can increase
      competitiveness of exotic plants, potentially increasing invasion success. We
      surveyed AMF abundance and community composition in Centaurea stoebe and
      Potentilla recta invasions in the western USA to assess whether patterns were
      consistent with mycorrhizal-mediated invasions. We asked whether (1) AMF
      abundance and community composition differ between native and exotic forbs, (2)
      associations between native plants and AMF shift with invading exotic plants, and
      (3) AMF abundance and/or community composition differ in areas where exotic
      plants are highly invasive and in areas where they are not. We collected soil and
      roots from invaded and native forb communities along invasion gradients and in
      regions with different invasion densities. We used AMF root colonization as a
      measure of AMF abundance and characterized AMF communities in roots using 454
      sequencing of the LSU-rDNA region. All plants were highly colonized (>60%), but
      exotic forbs tended to be more colonized than natives (P < 0.001). We identified
      30 AMF operational taxonomic units (OTUs) across sites, and community composition
      was best predicted by abiotic factors (soil texture, pH). Two OTUs in the genera
      Glomus and Rhizophagus dominated in most communities, and their dominance
      increased with invasion density (r = 0.57, P = 0.010), while overall OTU richness
      decreased with invasion density (r = -0.61, P = 0.006). Samples along P. recta
      invasion gradients revealed small and reciprocal shifts in AMF communities with
      >45% fungal OTUs shared between neighboring native and P. recta plants. Overall,
      we observed significant, but modest, differences in AMF colonization and
      communities between co-occurring exotic and native forbs and among exotic forbs
      across regions that differ in invasion pressure. While experimental manipulations
      are required to assess functional consequences, the observed patterns are not
      consistent with those expected from strong mycorrhizal-mediated invasions. 

PMID- 24683462
TI  - Endemicity and evolutionary value: a study of Chilean endemic vascular plant
      genera.
AB  - This study uses phylogeny-based measures of evolutionary potential (phylogenetic
      diversity and community structure) to evaluate the evolutionary value of vascular
      plant genera endemic to Chile. Endemicity is regarded as a very important
      consideration for conservation purposes. Taxa that are endemic to a single
      country are valuable conservation targets, as their protection depends upon a
      single government policy. This is especially relevant in developing countries in
      which conservation is not always a high resource allocation priority. Phylogeny
      based measures of evolutionary potential such as phylogenetic diversity (PD) have
      been regarded as meaningful measures of the "value" of taxa and ecosystems, as
      they are able to account for the attributes that could allow taxa to recover from
      environmental changes. Chile is an area of remarkable endemism, harboring a flora
      that shows the highest number of endemic genera in South America. We studied PD
      and community structure of this flora using a previously available supertree at
      the genus level, to which we added DNA sequences of 53 genera endemic to Chile.
      Using discrepancy values and a null model approach, we decoupled PD from taxon
      richness, in order to compare their geographic distribution over a one-degree
      grid. An interesting pattern was observed in which areas to the southwest appear
      to harbor more PD than expected by their generic richness than those areas to the
      north of the country. In addition, some southern areas showed more PD than
      expected by chance, as calculated with the null model approach. Geological
      history as documented by the study of ancient floras as well as glacial refuges
      in the coastal range of southern Chile during the quaternary seem to be
      consistent with the observed pattern, highlighting the importance of this area
      for conservation purposes. 

PMID- 24683463
TI  - Intraspecific competition and light effect on reproduction of Ligularia
      virgaurea, an invasive native alpine grassland clonal herb.
AB  - The relationship between sexual reproduction and clonal growth in clonal plants
      often shows up at the ramet level. However, only a few studies focus on the
      relationship at the genet level, which could finally account for evolution. The
      sexual reproduction and clonal growth of Ligularia virgaurea, a perennial herb
      widely distributed in the alpine grasslands of the Qinghai-Tibetan Plateau of
      China, were studied under different competition intensities and light conditions
      at the genet level through a potted experiment. The results showed that: (1)
      sexual reproduction did not depend on density or light, and increasing clonal
      growth with decreasing density and increasing light intensity indicated that
      intraspecific competition and light intensity may affect the clonal life history
      of L. virgaurea; (2) both sexual reproduction and clonal growth show a positive
      linear relationship with genet size under different densities and light
      conditions; (3) a threshold size is required for sexual reproduction and no
      evidence of a threshold size for clonal growth under different densities and
      light conditions; (4) light level affected the allocation of total biomass to
      clonal and sexual structures, with less allocation to clonal structures and more
      allocation to sexual structures in full sunlight than in shade; (5) light
      determined the onset of sexual reproduction, and the genets in the shade required
      a smaller threshold size for sexual reproduction to occur than the plants in full
      sunlight; and (6) no evidence was found of trade-offs between clonal growth and
      sexual reproduction under different densities and light conditions at the genet
      level, and the positive correlation between two reproductive modes indicated that
      these are two integrated processes. Clonal growth in this species may be viewed
      as a growth strategy that tends to maximize genet fitness. 

PMID- 24683464
TI  - An ecological cost associated with protective symbionts of aphids.
AB  - Beneficial symbioses are widespread and diverse in the functions they provide to
      the host ranging from nutrition to protection. However, these partnerships with
      symbionts can be costly for the host. Such costs, so called "direct costs", arise
      from a trade-off between allocating resources to symbiosis and other functions
      such as reproduction or growth. Ecological costs may also exist when symbiosis
      negatively affects the interactions between the host and other organisms in the
      environment. Although ecological costs can deeply impact the evolution of
      symbiosis, they have received little attention. The pea aphid Acyrthosiphon pisum
      benefits a strong protection against its main parasitoids from protective
      bacterial symbionts. The ecological cost of symbiont-mediated resistance to
      parasitism in aphids was here investigated by analyzing aphid behavior in the
      presence of predatory ladybirds. We showed that aphids harboring protective
      symbionts expressed less defensive behaviors, thus suffering a higher predation
      than symbiont-free aphids. Consequently, our study indicates that this underlined
      ecological cost may affect both the coevolutionary processes between symbiotic
      partners and the prevalence of such beneficial bacterial symbionts in host
      natural populations. 

PMID- 24683465
TI  - Interspecific diversity in root antioxidative enzyme activities reflect root
      turnover strategies and preferred habitats in wetland graminoids.
AB  - Antioxidant enzymes protect cells against oxidative stress and are associated
      with stress tolerance and longevity. In animals, variation in their activities
      has been shown to relate to species ecology, but in plants, comparative studies
      with wild species are rare. We investigated activities of five antioxidant
      enzymes - ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR),
      peroxidase (POX), and superoxide dismutase (SOD) - in roots of four perennial
      graminoid wetland species over a growing season to find out whether differences
      in root turnover or habitat preferences would be associated with variation in
      seasonal patterns of antioxidant enzyme activities. The investigated species
      differ in their root turnover strategies (fine roots senesce in the fall or fine
      roots survive the winter) and habitat preferences (nutrient-poor vs. productive
      wetlands). Roots were collected both in the field and from garden-grown plants.
      Antioxidant enzyme activities were higher and lipid peroxidation rates lower in
      species with annual root systems, and for species of the nutrient-poor wetland,
      compared with perennial roots and species of productive wetlands, respectively.
      There was variation in the activities of individual antioxidant enzymes, but
      discriminant analyses with all enzymes revealed a clear picture, indicating
      consistent associations of antioxidant enzyme activities with the type of root
      turnover strategy and with the preferred habitat. We conclude that antioxidant
      enzyme activities in plant roots are associated with the species' ecological
      strategies and can be used as traits for the characterization of the species'
      position along plant economics spectrum. 

PMID- 24683466
TI  - Adaptive latitudinal variation in Common Blackbird Turdus merula nest
      characteristics.
AB  - Nest construction is taxonomically widespread, yet our understanding of adaptive
      intraspecific variation in nest design remains poor. Nest characteristics are
      expected to vary adaptively in response to predictable variation in spring
      temperatures over large spatial scales, yet such variation in nest design remains
      largely overlooked, particularly amongst open-cup-nesting birds. Here, we
      systematically examined the effects of latitudinal variation in spring
      temperatures and precipitation on the morphology, volume, composition, and
      insulatory properties of open-cup-nesting Common Blackbirds' Turdus merula nests
      to test the hypothesis that birds living in cooler environments at more northerly
      latitudes would build better insulated nests than conspecifics living in warmer
      environments at more southerly latitudes. As spring temperatures increased with
      decreasing latitude, the external diameter of nests decreased. However, as nest
      wall thickness also decreased, there was no variation in the diameter of the
      internal nest cups. Only the mass of dry grasses within nests decreased with
      warmer temperatures at lower latitudes. The insulatory properties of nests
      declined with warmer temperatures at lower latitudes and nests containing greater
      amounts of dry grasses had higher insulatory properties. The insulatory
      properties of nests decreased with warmer temperatures at lower latitudes, via
      changes in morphology (wall thickness) and composition (dry grasses). Meanwhile,
      spring precipitation did not vary with latitude, and none of the nest
      characteristics varied with spring precipitation. This suggests that Common
      Blackbirds nesting at higher latitudes were building nests with thicker walls in
      order to counteract the cooler temperatures. We have provided evidence that the
      nest construction behavior of open-cup-nesting birds systematically varies in
      response to large-scale spatial variation in spring temperatures. 

PMID- 24683467
TI  - The case for character displacement in plants.
AB  - The evidence for character displacement as a widespread response to competition
      is now building. This progress is largely the result of the establishment of
      rigorous criteria for demonstrating character displacement in the animal
      literature. There are, however, relatively few well-supported examples of
      character displacement in plants. This review explores the potential for
      character displacement in plants by addressing the following questions: (1) Why
      aren't examples of character displacement in plants more common? (2) What are the
      requirements for character displacement to occur and how do plant populations
      meet those requirements? (3) What are the criteria for testing the pattern and
      process of character displacement and what methods can and have been used to
      address these criteria in the plant literature? (4) What are some additional
      approaches for studying character displacement in plants? While more research is
      needed, the few plant systems in which character displacement hypotheses have
      been rigorously tested suggest that character displacement may play a role in
      shaping plant communities. Plants are especially amenable to character
      displacement studies because of the experimental ease with which they can be used
      in common gardens, selection analyses, and breeding designs. A deeper
      investigation of character displacement in plants is critical for a more complete
      understanding of the ecological and evolutionary processes that permit the
      coexistence of plant species. 

PMID- 24683469
TI  - Exploring the Solid State Properties of Enzymatic Poly(amine-co-ester)
      Terpolymers to Expand their Applications in Gene Transfection.
AB  - Polymers bearing amino functional groups are an important class of materials
      capable of serving as non-viral carriers for DNA delivery to living cells. In
      this work biodegradable poly(amine-co-ester) terpolymers were synthesized via
      ring-opening and polycondensation copolymerization of lactone (epsilon
      caprolactone (CL), omega-dodecalactone, omega-pentadecalactone (PDL), and omega
      hexadecalactone) with diethyl sebacate (DES) and N-methyldiethanolamine (MDEA) in
      diphenyl ether, catalyzed by Candida antarctica lipase B (CALB). All lactone-DES
      MDEA terpolymers had random distributions of lactone, sebacate, MDEA repeat units
      in the polymer chains. PDL-DES-MDEA terpolymers were studied in the composition
      range from 21 mol% to 90 mol% PDL whereas the terpolymers with other lactones
      were investigated at a single composition (80 mol% lactone). DSC and WAXS
      analyses showed that all investigated terpolymers crystallize in their respective
      homopolylactone crystal lattice. Terpolymers with large lactones and a high
      lactone content melt well above room temperature and are hard solids, whereas
      terpolymers with small lactones (e.g. CL) or with a low lactone content melt
      below/around ambient temperature and are waxy/gluey materials. Given the
      importance of hydrophobicity in influencing gene delivery, water contact angle
      measurements were carried out on lactone-DES-MDEA terpolymers showing that it is
      possible to tune the hydrophilic-to-hydrophobic balance by varying polymer
      composition and size of lactone units. To demonstrate the feasibility of using
      solid terpolymers as nanocarriers for DNA delivery, PDL-DES-MDEA copolymers with
      65-90% PDL were successfully transformed into free-standing nanoparticles with
      average particle size ranging from 163 to 175 nm. Our preliminary results showed
      that LucDNA-loaded nanoparticles of the terpolymer with 65% PDL were effective
      for luciferase gene transfection of HEK293 cells.

PMID- 24683470
TI  - Nanoconjugation: A Materials Approach to Enhance Epidermal Growth Factor Induced
      Apoptosis.
AB  - Apoptosis evasion is a hallmark of cancer that motivates the development of novel
      strategies for inducing cell death in a controlled fashion. The size
      compatibility of nanoparticles (NPs) with cellular components provides new
      opportunities for regulating cellular processes, potentially including apoptosis.
      We investigated the impact of the covalent attachment of epidermal growth factor
      (EGF) to 40 nm diameter Au NPs on cellular apoptosis levels, quantified as
      caspase-3 activity, in two in vitro cancer cell lines: A431 and HeLa. Our studies
      show that nanoconjugation enhances EGF-induced apoptosis in EGF receptor (EGFR)
      overexpressing A431 and triggers a quantifiable increase in apoptosis in HeLa.
      The latter has physiological receptor expression levels and does not show
      apoptosis in response to free EGF. Endocytosis and trafficking are involved in
      key EGFR regulation processes, most prominently signal termination. Our
      experimental findings indicate that these processes can be manipulated through
      nanoconjugation to induce apoptosis.

PMID- 24683471
TI  - Beliefs about medicines among Norwegian outpatients with chronic cardiovascular
      disease.
AB  - OBJECTIVE: To investigate the beliefs of Norwegian outpatients about medicines,
      and to explore if some patient-specific factors and drug use are associated with
      the beliefs. METHODS: Patients from an outpatient clinic for chronic
      cardiovascular diseases were referred by physicians to a pharmacist-led
      medication outpatient clinic. Here the patients were asked to complete the
      Beliefs about Medicines Questionnaire. RESULTS: 150 patients were included (mean
      age 70.0 years (range 31-91), 50 (33.3%) women), using a total of 1061 drugs.
      91.2% strongly believed in the necessity of their medicines and 29.7% had strong
      concerns. Multivariate regression analyses showed that with an increasing number
      of drugs, the score for necessity was significantly increased (p<0.01). Women
      were significantly more concerned than men (p=0.03). The older the patient, the
      higher the score for general harm of medicines (p=0.01). CONCLUSIONS: Although
      the majority of the patients in this study believed in the necessity of their
      medication, one-third had strong concerns.

PMID- 24683472
TI  - Cardiovascular risk markers associated with arterial calcification in patients
      with chronic kidney disease Stages 3 and 4.
AB  - BACKGROUND: The contribution of pro-inflammatory markers to cardiovascular (CV)
      risk and vascular calcification in chronic kidney disease (CKD) remains largely
      to be elucidated. We investigated the association between plasma levels of
      several biomarkers and calcification volume in three different vascular beds in
      CKD Stages 3 and 4 patients. METHODS: This is a cross-sectional, exploratory
      study in patients with an estimated glomerular filtration rate (eGFR) >=20 and
      <=45 mL/min/1.73 m2 and serum phosphorus >=3.5 and <6.0 mg/dL enrolled in a
      previously published randomized, double blind, placebo-controlled single-centre
      trial. Ethylenediaminetetraacetic acid (EDTA) plasma samples were collected at
      baseline before patients received study medication and analysed for the presence
      of a number of biomarkers. Coronary artery calcium (CAC), thoracic aortic
      calcification (TAC) and abdominal aortic calcification (AAC) volumes were
      measured using standard electron-beam computed tomography protocols. Associations
      were adjusted for age, sex, smoking, body mass index, diabetes mellitus status,
      low-density lipoprotein cholesterol (LDL-C), systolic blood pressure and eGFR.
      RESULTS: Associations with CAC were found for beta2-microglobulin (B2M),
      fibroblast growth factor 23 (FGF23), interleukin-8 (IL-8) and IL-18. AAC was
      associated with: B2M, FGF23 and IL-2 receptor alpha (IL-2 RA). TAC was associated
      with: B2M, FGF23, IL-2 RA, IL-18 and tumour necrosis factor receptor type I. For
      most of the analysed biomarkers, there were non-significant trends of
      associations with calcification. CONCLUSIONS: This exploratory study found that
      elevated plasma levels of several inflammatory biomarkers are significantly
      associated with arterial calcification in CKD Stages 3 and 4 patients. A greater
      understanding of inflammation and calcification in CKD patients may help the
      development of CV risk-assessment algorithms for better management of these
      patients.

PMID- 24683473
TI  - Production and purification of the multifunctional enzyme horseradish peroxidase.
AB  - The oxidoreductase horseradish peroxidase (HRP) is used in numerous industrial
      and medical applications. In this review, we briefly describe this well-studied
      enzyme and focus on its promising use in targeted cancer treatment. In
      combination with a plant hormone, HRP can be used in specific enzyme-prodrug
      therapies. Despite this outstanding application, HRP has not found its way as a
      biopharmaceutical into targeted cancer therapy yet. The reasons therefore lie in
      the present low-yield production and cumbersome purification of this enzyme from
      its natural source. However, surface glycosylation renders the recombinant
      production of HRP difficult. Here, we compare different production hosts for HRP
      and summarize currently used production and purification strategies for this
      enzyme. We further present our own strategy of glycoengineering this powerful
      enzyme to allow recombinant high-yield production in Pichia pastoris and
      subsequent simple downstream processing.

PMID- 24683474
TI  - Multiple Hurthle cell adenomas in a patient with thyroid hormone resistance.
AB  - BACKGROUND: Thyroid hormone resistance (RTH) is a rare cause of thyroid
      dysfunction. High TSH levels, as described in RTH syndrome, are known to be
      associated with an increased risk of developing thyroid nodules with subsequent
      growth and malignancy. PATIENT FINDINGS: In 2006, a 29-year-old Caucasian man
      presented with a palpable mass in the neck. Increased free thyroxine and
      triiodothyronine levels were found in the context of unsuppressed TSH levels,
      despite no signs or symptoms of hyperthyroidism. Ultrasonography revealed a
      multinodular and enlarged goitre, and fine-needle aspiration cytology revealed
      suspicious features of malignancy. After excluding pituitary tumour and
      levothyroxine (l-T4) treatment, the patient was diagnosed with generalized RTH.
      Screening for all the known mutations in thyroid hormone receptor-beta (TR beta
      (THRB)) was negative. Thyroidectomy disclosed five Hurthle adenomas and three
      hyperplasic nodules. Euthyroidism was achieved after surgery with 6.1 MUg/kg per
      day of l-T4. CONCLUSION: RTH may be a risk factor that predisposes to the
      development of multiple Hurthle cell adenomas. To our knowledge, this is the
      first case of multiple Hurthle cell adenomas in a patient with RTH. LEARNING
      POINTS: High TSH levels, as described in RTH syndrome, are known to be associated
      with an increased risk of developing thyroid nodules, with subsequent growth and
      malignancy.The exact role of TR beta mutants in thyroid carcinogenesis is still
      undefined.We report the first case of multiple Hurthle cell adenomas associated
      with RTH.

PMID- 24683475
TI  - Vanishing large ovarian cyst with thyroxine therapy.
AB  - A 21-year-old female patient recently diagnosed with severe hypothyroidism was
      found to have a large ovarian cyst. In view of the large ovarian cyst, she was
      advised to undergo elective laparotomy in the gynaecology department. She was
      further evaluated in our medical out-patient department (OPD), and elective
      surgery was withheld. She was started on thyroxine replacement therapy, and
      within a period of 4 months, the size of the cyst regressed significantly,
      thereby improving the condition of the patient significantly. This case report
      highlights the rare and often missed association between hypothyroidism and
      ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian
      cysts in an adult should always be kept in the differential diagnosis to avoid
      unnecessary ovarian surgery. LEARNING POINTS: Hypothyroidism should be considered
      in the differential diagnosis of adult females presenting with multicystic
      ovarian tumours.Adequate thyroid hormone replacement therapy can prevent these
      patients from undergoing unnecessary and catastrophic ovarian resection.Surgical
      excision should be considered only when adequate thyroid replacement therapy
      fails to resolve ovarian enlargement.In younger women with ovarian cysts, it is
      also desirable to avoid unnecessary surgery so as to not compromise fertility in
      the future.

PMID- 24683477
TI  - Recovery of adrenal function in a patient with confirmed Addison's disease.
AB  - Addison's disease is a condition characterised by immune-mediated destruction of
      the adrenal glands leading to a requirement of lifelong replacement therapy with
      mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who
      presented at the age of 37 years with nausea, fatigue and dizziness. He was found
      to have postural hypotension and buccal pigmentation. His presenting cortisol
      level was 43 nmol/l with no response to Synacthen testing. He made an excellent
      response to conventional replacement therapy with hydrocortisone and
      fludrocortisone and then remained well for 16 years. On registering with a new
      endocrinologist, his hydrocortisone dose was revised downwards and pre- and post
      dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly
      elevated, and so his dose was further reduced. Subsequent Synacthen testing was
      normal and has remained so for further 12 months. He is now asymptomatic without
      glucocorticoid therapy, although he continues on fludrocortisone 50 MUg daily.
      His adrenal antibodies are positive, although his ACTH and renin levels remain
      elevated after treatment. Addison's disease is generally deemed to lead to
      irreversible cell-mediated immune destruction of the adrenal glands. For this
      reason, patients receive detailed counselling and education on the need for
      lifelong replacement therapy. To our knowledge, this is the third reported case
      of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may
      therefore be more common than previously appreciated, which may have major
      implications for the treatment and monitoring of this condition, and for the
      education given to patients at diagnosis. LEARNING POINTS: Partial recovery from
      Addison's disease is possible although uncommon.Patients with long-term endocrine
      conditions on replacement therapy still benefit from regular clinical and
      biochemical assessment, to revisit optimal management.As further reports of
      adrenal axis recovery emerge, this may influence the counselling given to
      patients with Addison's disease in the future.

PMID- 24683476
TI  - Continuous glucose monitoring in the treatment of obesity in patients with
      glycogen storage disease type Ia.
AB  - Glycogen storage disease (GSD) type I is characterized by impaired production of
      glucose from glycogenolysis and gluconeogenesis resulting in severe hypoglycaemia
      and increased production of lactic acid, triglyceride and uric acid. The most
      common type, glycogenosis type Ia, demands a balanced, sufficient carbohydrate
      intake to preserve normal 24-h glycaemia. Insufficient intake of carbohydrates
      can cause hypoglycaemia, as the missing glucose-6-phosphatase enzyme cannot free
      the glucose stored as liver glycogen and nor is gluconeogenesis possible. The
      principle means of handling this disorder is to avoid starving by taking regular
      meals during the day and night. Such a dietary regimen could lead to obesity.
      Herein, we present the case of an adult patient with glycogenosis type Ia
      suffering from hyperuricaemia, dyslipidaemia and arterial hypertension. The
      accumulation of these cardiovascular risk factors could lead to the early onset
      of atherosclerosis, which should be postponed by contemporary methods of
      surveillance and treatment. LEARNING POINTS: Continuous subcutaneous glucose
      monitoring may be of value in every adult patient with GSD type I to evaluate the
      actual prevalence of eventual hypoglycaemic and hyperglycaemic episodes.Good
      dietary management minimizes the metabolic abnormalities of the disease and
      decreases the risk of long-term complications.Treatment of obesity in patients
      with GSD reduces the risk of earlier atherosclerosis and cardiovascular disease.

PMID- 24683478
TI  - Two patients with atypical low triiodothyronine syndrome: primary deiodinase
      abnormalities?
AB  - Low triiodothyronine (T3) concentrations in the presence of normal thyroxine (T4)
      and TSH levels, referred to as the low T3 syndrome (LT3S), are common. LT3S may
      be caused by starvation, various non-thyroidal illnesses (NTIs) and some
      medications. Reverse T3 (rT3) concentrations are elevated in the more severely
      ill, and they characteristically fail to respond to exogenous levothyroxine (l
      T4) therapy. The biochemical abnormalities have been explained on the basis of
      altered peripheral deiodinase activities. Herein, we report on two patients with
      hypothyroid symptoms who on testing were found to have LT3S. They were atypical
      clinically in not having LT3S due to any of the usual causes, had no increased
      rT3 concentrations, and had a normal negative TSH feedback response to l-T4. One
      (patient 1) had previously been diagnosed with Hashimoto's autoimmune primary
      hypothyroidism and was on l-T4 therapy. Both had T4 concentrations in the
      reference range. TSH levels were elevated in patient 1 and in the reference range
      in patient 2. Starting or increasing l-T4 doses resulted in no clinical
      improvement and no increase in T3 levels in spite of a marked increase in T4
      levels. It is suggested that in the absence of the usual causes, lack of elevated
      rT3 levels, response to treatment and intact negative TSH feedback these two
      patients differ from the usual secondary causes of decreases in deiodinase
      activity. It is speculated that they may represent primary alterations in
      deiodinase enzymes possibly due to genetic variations in the deiodinase-encoding
      genes. LEARNING POINTS: LT3S is commonly found secondary to starvation, NTIs and
      use of some medications.Low T3 levels are the result of alterations in the
      activity of deiodinase enzymes.LT3S without the usual causes may represent a
      primary disturbance in deiodinase activity.

PMID- 24683479
TI  - Clinical challenges in the management of isolated GH deficiency type IA in
      adulthood.
AB  - Isolated GH deficiency type IA (IGHDIA) is an infrequent cause of severe
      congenital GHD, often managed by pediatric endocrinologists, and hence few cases
      in adulthood have been reported. Herein, we describe the clinical status of a 56
      year-old male with IGHDIA due to a 6.7 kb deletion in GH1 gene that encodes GH,
      located on chromosome 17. We also describe phenotypic and biochemical parameters,
      as well as characterization of anti-GH antibodies after a new attempt made to
      treat with GH. The height of the adult patient was 123 cm. He presented with type
      2 diabetes mellitus, dyslipidemia, osteoporosis, and low physical and
      psychological performance, compatible with GHD symptomatology. Anti-GH antibodies
      in high titers and with binding activity (>101 IU/ml) were found 50 years after
      exposure to exogenous GH, and their levels increased significantly (>200 U/ml)
      after a 3-month course of 0.2 mg/day recombinant human GH (rhGH) treatment.
      Higher doses of rhGH (1 mg daily) did not overcome the blockade, and no change in
      undetectable IGF1 levels was observed (<25 ng/ml). IGHDIA patients need lifelong
      medical surveillance, focusing mainly on metabolic disturbances, bone status,
      cardiovascular disease, and psychological support. Multifactorial conventional
      therapy focusing on each issue is recommended, as anti-GH antibodies may
      inactivate specific treatment with exogenous GH. After consideration of potential
      adverse effects, rhIGF1 treatment, even theoretically indicated, has not been
      considered in our patient yet. LEARNING POINTS: Severe isolated GHD may be caused
      by mutations in GH1 gene, mainly a 6.7 kb deletion.Appearance of neutralizing
      anti-GH antibodies upon recombinant GH treatment is a characteristic feature of
      IGHDIA.Recombinant human IGF1 treatment has been tested in children with IGHDIA
      with variable results in height and secondary adverse effects, but any occurrence
      in adult patients has not been reported yet.Metabolic disturbances (diabetes and
      hyperlipidemia) and osteoporosis should be monitored and properly treated to
      minimize cardiovascular disease and fracture risk.Cerebral magnetic resonance
      imaging should be repeated in adulthood to detect morphological abnormalities
      that may have developed with time, as well as pituitary hormones periodically
      assessed.

PMID- 24683480
TI  - Thromboembolic complications of thyroid storm.
AB  - Thyroid storm is a rare but potentially life-threatening complication of
      hyperthyroidism. Early recognition and prompt treatment are essential. Atrial
      fibrillation can occur in up to 40% of patients with thyroid storm. Studies have
      shown that hyperthyroidism increases the risk of thromboembolic events. There is
      no consensus with regard to the initiation of anticoagulation for atrial
      fibrillation in severe thyrotoxicosis. Anticoagulation is not routinely initiated
      if the risk is low on a CHADS2 score; however, this should be considered in
      patients with thyroid storm or severe thyrotoxicosis with impending storm
      irrespective of the CHADS2 risk, as it appears to increase the risk of
      thromboembolic episodes. Herein, we describe a case of thyroid storm complicated
      by massive pulmonary embolism. LEARNING POINTS: Diagnosis of thyroid storm is
      based on clinical findings. Early recognition and prompt treatment could lead to
      a favourable outcome.Hypercoagulable state is a recognised complication of
      thyrotoxicosis.Atrial fibrillation is strongly associated with hyperthyroidism
      and thyroid storm.Anticoagulation should be considered for patients with severe
      thyrotoxicosis and atrial fibrillation irrespective of the CHADS2 score.Patients
      with severe thyrotoxicosis and clinical evidence of thrombosis should be
      immediately anticoagulated until hyperthyroidism is under control.

PMID- 24683481
TI  - A man with a worrying potassium deficiency.
AB  - Hypokalaemia may present as muscle cramps and Cardiac arrhythmias. This is a
      condition commonly encountered by endocrinologists and general physicians alike.
      Herein, we report the case of a 43-year-old gentleman admitted with hypokalaemia,
      who following subsequent investigations was found to have Gitelman's syndrome
      (GS). This rare, inherited, autosomal recessive renal tubular disorder is
      associated with genetic mutations in the thiazide-sensitive sodium chloride co
      transporter and magnesium channels in the distal convoluted tubule. Patients with
      GS typically presents at an older age, and a spectrum of clinical presentations
      exists, from being asymptomatic to predominant muscular symptoms. Clinical
      suspicion should be raised in those with hypokalaemic metabolic alkalosis
      associated with hypomagnesaemia. Treatment of GS consists of long-term potassium
      and magnesium salt replacement. In general, the long-term prognosis in terms of
      preserved renal function and life expectancy is excellent. Herein, we discuss the
      biochemical imbalance in the aetiology of GS, and the case report highlights the
      need for further investigations in patients with recurrent hypokalaemic episodes.
      LEARNING POINTS: Recurrent hypokalaemia with no obvious cause warrants
      investigation for hereditary renal tubulopathies.GS is the most common inherited
      renal tubulopathy with a prevalence of 25 per million people.GS typically
      presents at an older age and clinical suspicion should be raised in those with
      hypokalaemic metabolic alkalosis associated with hypomagnesaemia.Confirmation of
      diagnosis is by molecular analysis for mutation in the SLC12A3 gene.

PMID- 24683482
TI  - Adrenal insufficiency in acute oral opiate therapy.
AB  - Opiate drugs such as morphine are in extensive use for pain relief and
      palliation. It is well established that these drugs can cause changes in
      endocrine function, but such effects are not always sufficiently appreciated in
      clinical practice, especially in relation to the hypothalamic-pituitary-adrenal
      (HPA) axis. Herein, we report on an 18-year-old man who was diagnosed with a
      slipped left femoral epiphysis following a long history of pain in his leg. On
      examination, he was thought to look relatively young for his age and therefore
      the orthopaedic surgeons arranged an endocrine assessment, which showed an
      undetectable concentration of serum cortisol and a suppressed concentration of
      testosterone; therefore, he was referred urgently with a diagnosis of
      hypopituitarism. We elicited a history that he had been treated with opiate
      analgesics for 3 days at the time of his original blood tests. Full endocrine
      assessment including a short Synacthen test revealed that he now had normal
      adrenal and pituitary function. We conclude that his morphine therapy had caused
      profound suppression of his HPA and pituitary-gonadal axes and suggest that
      clinicians should be aware of these significant changes in patients on even short
      term opiate therapy. LEARNING POINTS: Therapy with opiates is the standard
      therapy for severe acute and chronic pain.Such drugs cause profound changes in
      endocrine function.Importantly, opiates suppress the HPA axis at a central
      level.Short-term therapy with morphine could be the cause of biochemical
      adrenocortical insufficiency.Morphine and related drugs also suppress the
      pituitary-gonadal axis.After discontinuation of therapy with such drugs, adrenal
      function improves.

PMID- 24683483
TI  - Dense calcification in a GH-secreting pituitary macroadenoma.
AB  - A 30-year-old female presented with a history of secondary amenorrhoea,
      acromegalic features and progressive visual deterioration. She had elevated serum
      IGF1 levels and unsuppressed GH levels after an oral glucose tolerance test.
      Magnetic resonance imaging revealed a heterogeneously enhancing space-occupying
      lesion with atypical extensive calcification within the sellar and suprasellar
      areas. Owing to the extent of calcification, the tumour was a surgical challenge.
      Postoperatively, there was clinical, radiological and biochemical evidence of
      residual disease, which required treatment with a somatostatin analogue and
      radiotherapy. Mutational analysis of the aryl hydrocarbon receptor-interacting
      protein (AIP) gene was negative. This case confirms the relatively rare
      occurrence of calcification within a pituitary macroadenoma and its associated
      management problems. The presentation, biochemical, radiological and pathological
      findings are discussed in the context of the relevant literature. LEARNING
      POINTS: Calcification of pituitary tumours is relatively rare.Recognising
      calcification in pituitary adenomas on preoperative imaging is important in
      surgical decision-making.Gross total resection can be difficult to achieve in the
      presence of extensive calcification and dictates further management and follow-up
      to achieve disease control.

PMID- 24683484
TI  - Adrenal insufficiency in a woman secondary to standard-dose inhaled fluticasone
      propionate therapy.
AB  - A 55-year-old woman with asthma presented with adrenal insufficiency of unknown
      origin. She was referred to our Division of Reproductive Endocrinology to further
      evaluate an undetectable morning cortisol level discovered during the evaluation
      of a low serum DHEA-S level. She was asymptomatic other than having mild fatigue
      and weight gain. Her medication list included 220 MUg of inhaled fluticasone
      propionate twice daily for asthma, which she was taking as prescribed. On
      presentation, the undetectable morning cortisol level was confirmed. A urinary
      measurement of fluticasone propionate 17beta-carboxylic acid was markedly
      elevated. Fluticasone therapy was discontinued and salmeterol therapy initiated
      with supplemental hydrocortisone. Hydrocortisone therapy was discontinued after 2
      months. A repeat urinary fluticasone measurement 4 months after the
      discontinuation of fluticasone therapy was undetectably low and morning cortisol
      level was normal at 18.0 MUg/dl. Inhaled fluticasone is generally considered to
      be minimally systemically absorbed. This patient's only clinical evidence
      suggesting adrenal insufficiency was fatigue accompanying a low serum DHEA-S
      level. This case demonstrates that adrenal insufficiency can be caused by a
      routine dose of inhaled fluticasone. Missing this diagnosis could potentially
      result in adrenal crisis upon discontinuation of fluticasone therapy. LEARNING
      POINTS: Standard-dose inhaled fluticasone can cause adrenal insufficiency.Adrenal
      insufficiency should be considered in patients taking, or who have recently
      discontinued, inhaled fluticasone therapy and present with new onset of
      nonspecific symptoms such as fatigue, weakness, depression, myalgia, arthralgia,
      unexplained weight loss, and nausea that are suggestive of adrenal
      insufficiency.Adrenal insufficiency should be considered in postoperative
      patients who exhibit signs of hypoadrenalism after fluticasone therapy has been
      withheld in the perioperative setting.Routine screening for hypoadrenalism in
      patients without clinical signs or symptoms of adrenal insufficiency after the
      discontinuation of inhaled fluticasone therapy is not indicated due to the
      apparently low incidence of adrenal insufficiency caused by fluticasone.

PMID- 24683485
TI  - A case of insulin and ACTH co-secretion by a neuroendocrine tumour.
AB  - A 33-year-old male was diagnosed with a metastatic neuroendocrine carcinoma of
      uncertain primary. He defaulted from follow-up without therapy and some months
      later developed episodic severe hypoglycaemia, which was found to be associated
      with inappropriately elevated insulin and C-peptide levels. It was considered
      likely that the neuroendocrine tumour was the source of the insulin secretion.
      Diazoxide and somatostatin analogue were used to control hypoglycaemia. Much
      later in the course of the disease, he developed metabolic derangement, increased
      skin pigmentation and psychological disturbance, without frankly Cushingoid
      physical findings. Investigations revealed highly elevated cortisol levels (the
      levels having previously been normal) with markedly raised ACTH levels,
      consistent with the co-secretion of ACTH and insulin by the tumour. Treatment
      with metyrapone improved his psychological state and electrolyte imbalance.
      Unfortunately, despite several cycles of first-, second- and third-line
      chemotherapy from the start of the first hormonal presentation onwards, imaging
      revealed widespread progressive metastatic disease and the patient eventually
      passed away. This case highlights the importance of keeping in mind the
      biochemical heterogeneity of endocrine tumours during their treatment. LEARNING
      POINTS: The clinical presentation of insulin-secreting tumours includes symptoms
      of neuroglycopaenia and sympathetic overstimulation.Tumour-associated
      hypoglycaemia can be due to pancreatic insulinomas, and although ectopic hormone
      production occurs in a number of tumours, ectopic secretion of insulin is rare.A
      possible switch in the type of hormone produced can occur during the growth and
      progression of neuroendocrine tumours and, when treating neuroendocrine tumours,
      it is important to keep in mind their biochemical heterogeneity.

PMID- 24683486
TI  - Radioiodine treatment of differentiated thyroid cancer despite history of 'iodine
      allergy'.
AB  - Radioiodine ((131)I) is a critical component in the treatment of differentiated
      thyroid cancer. We recently saw a patient with thyroid cancer who was hesitant to
      take (131)I treatment because he had previously encountered an allergic reaction
      to administration of iodine-containing radiocontrast agent for computed
      tomography (CT) scanning. We were able to administer (131)I treatment after
      discussion that his anaphylactic reaction was not due to iodine and that
      radioiodine ((131)I) treatment is unlikely to cause a reaction in the patient.
      LEARNING POINTS: An allergy to iodine itself does not exist.When patients claim
      that they have an 'iodine allergy', ask them what substances they are allergic to
      and what kind of reaction occurred during use of such substances.Radioactive
      iodine is not a contraindication for patients who claim an 'allergy to iodine'.

PMID- 24683487
TI  - A case of ectopic ACTH syndrome treated with intermittent administration of
      dopamine agonists.
AB  - ACTH-dependent Cushing's syndrome includes Cushing's disease and ectopic ACTH
      syndrome (EAS). The differential diagnosis of Cushing's disease from EAS in cases
      of ACTH-dependent Cushing's syndrome is a challenging problem. We report here a
      case of EAS with an unknown source of ACTH secretion. Extensive imaging
      procedures, involving computed tomography (neck to pelvis), pituitary magnetic
      resonance imaging, and whole-body (18)F-fluorodeoxyglucose-positron emission
      tomography, failed to reveal the source of ACTH secretion. Intermittent
      administration of bromocriptine, a short-acting and nonselective dopamine
      agonist, has afforded adequate suppression of plasma ACTH and cortisol levels
      over the long term. LEARNING POINTS: Tumor excision is the primary treatment for
      EAS. However, when surgery is impossible, medical therapy is needed to treat
      hypercortisolism.In cases where the source of ACTH secretion is unknown,
      inhibitors of steroidogenesis, such as metyrapone, mitotane, ketoconazole, and
      etomidate, are mostly used to suppress cortisol secretion.Medications that
      suppress ACTH secretion are less effective, therefore less popular, as standard
      treatments.In the present case, short-term treatment with dopamine agonists was
      effective for the long-term suppression of both ACTH and cortisol levels.

PMID- 24683488
TI  - Dynamic mass redistribution analysis of endogenous beta-adrenergic receptor
      signaling in neonatal rat cardiac fibroblasts.
AB  - Label-free systems for the agnostic assessment of cellular responses to receptor
      stimulation have been shown to provide a sensitive method to dissect receptor
      signaling. beta-adenergic receptors (betaAR) are important regulators of normal
      and pathologic cardiac function and are expressed in cardiomyocytes as well as
      cardiac fibroblasts, where relatively fewer studies have explored their signaling
      responses. Using label-free whole cell dynamic mass redistribution (DMR) assays
      we investigated the response patterns to stimulation of endogenous betaAR in
      primary neonatal rat cardiac fibroblasts (NRCF). Catecholamine stimulation of the
      cells induced a negative DMR deflection resulting in a concentration-dependent
      pharmacological response that was competitively blocked by betaAR blockade and
      non-competitively blocked by irreversible uncoupling of Gs proteins.
      Pharmacological profiling of subtype-selective betaAR agonists and antagonists
      revealed a dominant role of beta2AR in mediating the DMR responses, consistent
      with the relative expression levels of beta2AR and beta1AR in NRCF. Additionally,
      betaAR-mediated cAMP generation was assessed via a fluorescence biosensor,
      revealing similar kinetics between DMR responses and cAMP generation. As such,
      betaAR-dependent DMR responses were enhanced via inhibition of cAMP degradation,
      as well as dynamin-mediated receptor internalization. Finally, we assessed G
      protein-independent betaAR signaling through epidermal growth factor receptor
      (EGFR). While inhibition of EGFR reduced the DMR response to betaAR stimulation,
      our results demonstrate that G protein-dependent signaling produces a majority of
      the biological response to betaAR stimulation in NRCF. Altogether, measurement of
      DMR responses in primary cardiac fibroblasts provides a sensitive readout for
      investigating endogenous betaAR signaling via both G protein-dependent and 
      independent pathways.

PMID- 24683489
TI  - The past, present, and future of human centromere genomics.
AB  - The centromere is the chromosomal locus essential for chromosome inheritance and
      genome stability. Human centromeres are located at repetitive alpha satellite DNA
      arrays that compose approximately 5% of the genome. Contiguous alpha satellite
      DNA sequence is absent from the assembled reference genome, limiting current
      understanding of centromere organization and function. Here, we review the
      progress in centromere genomics spanning the discovery of the sequence to its
      molecular characterization and the work done during the Human Genome Project era
      to elucidate alpha satellite structure and sequence variation. We discuss
      exciting recent advances in alpha satellite sequence assembly that have provided
      important insight into the abundance and complex organization of this sequence on
      human chromosomes. In light of these new findings, we offer perspectives for
      future studies of human centromere assembly and function. 

PMID- 24683490
TI  - Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related
      Potential (ERP) Indices of Attention in Autism.
AB  - Individuals with autism spectrum disorder (ASD) have previously been shown to
      have significantly augmented and prolonged event-related potentials (ERP) to
      irrelevant visual stimuli compared to controls at both early and later stages
      (e.g., N200, P300) of visual processing and evidence of an overall lack of
      stimulus discrimination. Abnormally large and indiscriminative cortical responses
      to sensory stimuli may reflect cortical inhibitory deficits and a disruption in
      the excitation/inhibition ratio. Low-frequency (<=1HZ) repetitive transcranial
      magnetic stimulation (rTMS) has been shown to increase inhibition of stimulated
      cortex by the activation of inhibitory circuits. It was our prediction that after
      12 sessions of low-frequency rTMS applied bilaterally to the dorsolateral
      prefrontal cortices in individuals with ASD there would be a significant
      improvement in ERP indices of selective attention evoked at later (i.e., 200-600
      ms) stages of attentional processing as well as an improvement in motor response
      error rate. We assessed 25 participants with ASD in a task of selective attention
      using illusory figures before and after 12 sessions of rTMS in a controlled
      design where a waiting-list group of 20 children with ASD performed the same task
      twice. We found a significant improvement in both N200 and P300 components as a
      result of rTMS as well as a significant reduction in response errors. We also
      found significant reductions in both repetitive behavior and irritability
      according to clinical behavioral questionnaires as a result of rTMS. We propose
      that rTMS has the potential to become an important therapeutic tool in ASD
      research and treatment.

PMID- 24683492
TI  - Blindness and Visual Impairment among Egyptian Glaucoma Patients.
AB  - Purpose. Glaucoma is the second commonest cause of blindness worldwide. Visual
      fields and intraocular pressures are optimum outcomes to be assessed in developed
      countries. Visual acuity as an outcome is the key player when assessing blindness
      in developing countries. The aim of this study is to assess visual impairment and
      blindness in glaucoma patients and to identify the bulk they represent in
      comparison to nonglaucoma patients in the same practice setting. Methods.
      Patients attending outpatient clinics of Cairo University Hospitals were enrolled
      in this cross-sectional study. Clinical data collected for these patients
      included their demographic data, best obtained visual acuity, and whether or not
      they have had an established diagnosis of glaucoma. Results were compared at 95%
      confidence intervals. Results. 988 eyes of 494 patients were included for this
      study. Their mean visual acuity was 6/24 (+/-3 Snellen lines). Legal blindness
      was found in 5% and 4% of glaucoma and nonglaucoma groups, respectively. There
      were high odds for finding eyes with total blindness due to glaucoma. That was
      statistically significant (P < 0.05). Conclusions. A large proportion of glaucoma
      patients suffered from blindness in at least one eye. Interventional strategies
      are recommended regarding visual disability among Egyptian glaucoma patients. 

PMID- 24683491
TI  - Uveitis and gender: the course of uveitis in pregnancy.
AB  - The hormonal and immunological changes in pregnancy have a key role in
      maintaining maternal tolerance of the semiallogeneic foetus. These pregnancy
      associated changes may also influence the course of maternal autoimmune diseases.
      Noninfectious uveitis tends to improve during pregnancy. Specifically, uveitis
      activity tends to ameliorate from the second trimester onwards, with the third
      trimester being associated with the lowest disease activity. The mechanism behind
      this phenomenon is likely to be multifactorial and complex. Possible mechanisms
      include Th1/Th2 immunomodulation, regulatory T-cell phenotype plasticity, and
      immunosuppressive cytokines. This clearly has management implications for
      patients with chronic sight threatening disease requiring systemic treatment, as
      most medications are not recommended during pregnancy due to lack of safety data
      or proven teratogenicity. Given that uveitis activity is expected to decrease in
      pregnancy, systemic immunosuppressants could be tapered during pregnancy in these
      patients, with flare-ups being managed with local corticosteroids till delivery.
      In the postpartum period, as uveitis activity is expected to rebound, patients
      should be reviewed closely and systemic medications recommenced, depending on
      uveitis activity and the patient's breastfeeding status. This review highlights
      the current understanding of the course of uveitis in pregnancy and its
      management to help guide clinicians in managing their uveitis patients during
      this special time in life. 

PMID- 24683493
TI  - Prediction of driving safety in individuals with homonymous hemianopia and
      quadrantanopia from clinical neuroimaging.
AB  - Background. This study aimed to determine whether it is possible to predict
      driving safety of individuals with homonymous hemianopia or quadrantanopia based
      upon a clinical review of neuroimages that are routinely available in clinical
      practice. Methods. Two experienced neuroophthalmologists viewed a summary report
      of the CT/MRI scans of 16 participants with homonymous hemianopic or
      quadrantanopic field defects which indicated the site and extent of the lesion
      and they made predictions regarding whether participants would be safe/unsafe to
      drive. Driving safety was independently defined at the time of the study using
      state-recorded motor vehicle crashes (all crashes and at-fault) for the previous
      5 years and ratings of driving safety determined through a standardized on-road
      driving assessment by a certified driving rehabilitation specialist. Results. The
      ability to predict driving safety was highly variable regardless of the driving
      safety measure, ranging from 31% to 63% (kappa levels ranged from -0.29 to 0.04).
      The level of agreement between the neuroophthalmologists was only fair (kappa =
      0.28). Conclusions. Clinical evaluation of summary reports of currently available
      neuroimages by neuroophthalmologists is not predictive of driving safety. Future
      research should be directed at identifying and/or developing alternative tests or
      strategies to better enable clinicians to make these predictions. 

PMID- 24683494
TI  - Corneal endothelial cell density and morphology in healthy Turkish eyes.
AB  - Purpose. To describe the normative values of corneal endothelial cell density,
      morphology, and central corneal thickness in healthy Turkish eyes. Methods.
      Specular microscopy was performed in 252 eyes of 126 healthy volunteers (M : F,
      42 : 84). Parameters studied included mean endothelial cell density (MCD), mean
      cell area (MCA), coefficient of variation (CV) in cell size, percentage of
      hexagonal cells, and central corneal thickness (CCT). Results. The mean age of
      volunteers was 44.3 +/- 13.5 (range, 20 to 70) years. There was a statistically
      significant decrease in MCD (P < 0.001; correlation, -0.388) and percentage of
      hexagonal cells, (P < 0.001; correlation, -0.199) with age. There was also a
      statistically significant increase in MCA (P < 0.001; correlation, 0.363) with
      increasing age. There was no statistically significant difference in MCD, MCA, CV
      in cell size, percentage of hexagonal cells, and CCT between genders and there
      was also no significant difference in these parameters between fellow eyes of
      subjects. Conclusions. Normotive data for the endothelium in the Turkish
      population are reported. Endothelial cell density in the Turkish eyes is less
      than that described in the Japanese, American, Chinese, and Filipino eyes and
      higher than that described in Indian, Thai, and Iranian eyes. 

PMID- 24683495
TI  - Correlations between ERG, OCT, and Anatomical Findings in the rd10 Mouse.
AB  - Background. To evaluate the correlation between ERG, OCT, and microscopic
      findings in the rd10 mouse. Methods. C57BL/6J wild type mice and rd10 mice were
      compared at the age of 2, 3, 5, 7, 9, 12, 24, and 48 weeks (each age group n = 3)
      using full-field electroretinography (ERG), spectral domain Optical Coherence
      Tomography (sd-OCT), fluorescein angiography (FA), Hematoxylin & Eosin histology
      (HE), and immunohistology (IH). Results. While in wild type mice, the amplitude
      of a- and b-wave increased with light intensity and with the age of the animals,
      the rd10 mice showed extinction of the ERG beginning with the age of 5 weeks. In
      OCT recordings, the thickness of the retina decreased up to 9 weeks of age,
      mainly based on the degradation of the outer nuclear layer (ONL). Afterwards, the
      ONL was no longer visible in the OCT. HE staining and immunohistological findings
      confirmed the in vivo data. Conclusion. ERG and OCT are useful methods to
      evaluate the retinal function and structure in vivo. The retinal changes seen in
      the OCT closely match those observed in histological staining. 

PMID- 24683496
TI  - Analysis of the Distribution and Temporal Trends of Grade and Stage in Urothelial
      Bladder Cancer in Northern New England from 1994 to 2004.
AB  - We investigate the distribution of bladder tumor category and stage in Northern
      New England by geographic region, smoking status and over time. 1091 incident
      bladder cancer cases from the New England Bladder Cancer Study (NEBCS), a large
      population-based case-control study carried out in Maine, New Hampshire and
      Vermont (2001-2004), and 680 bladder cancer cases from previous case-control
      studies in New Hampshire (1994-2000) were used in the analysis. Of 1091 incident
      bladder cancer cases from the NEBCS, 26.7% of tumors were papillary urothelial
      neoplasms of low malignant potential (PUNLMP), 26.8% low-grade papillary
      urothelial carcinomas (PUC-LG), 31.3% high-grade papillary urothelial carcinomas
      (PUC-HG), 9.1% non-papillary urothelial carcinomas (non-PUC), and 4.3% carcinoma
      in situ (CIS). Approximately 70% of cases were non-invasive (Tis/Ta), and all
      PUNLMP cases were of the Ta category. By contrast, half of all PUC-HG carcinomas
      were invasive. Short-term time trend analysis within the NEBCS (2001-2004)
      indicated an increase in the percentage of PUNLMP (p-trend<0.0001) paralleled by
      a decrease in PUC-LG (p-trend=0.02), and for PUC-LG an increase in the percentage
      of non-invasive tumors (p-trend 0.04). Our findings suggest possible short-term
      trends with an increase in the percentage of PUNLMP and a change in the
      percentage of PUC-LG towards non-invasive disease.

PMID- 24683497
TI  - The effect of fasting on PET Imaging of Hepatocellular Carcinoma.
AB  - : The clinical utility of positron emission tomography (PET) imaging for liver
      cancer applications is not clearly defined either for diagnosis or treatment
      assessment. Previous clinical studies demonstrated that fluorodeoxyglucose (FDG)
      did not show uptake in some hepatocellular carcinoma (HCC) while acetate showed
      uptake. Pre-imaging fasting is required for clinical PET imaging with FDG. No
      studies were done to confirm the effect of fasting on acetate uptake in HCC for
      PET imaging. We investigated this situation with a woodchuck model of viral
      infection-induced HCC. METHODS: Four tumor-bearing and one control woodchucks
      were involved in this study. They were first imaged by PET in fed state followed
      by another imaging session one week later when they were fasted over-night. Some
      animals also had FDG-PET scan that was acquired later on the same day. After
      imaging studies, animals were sacrificed, and their liver excised for histology.
      Standardized Uptake Value (SUV) was calculated using a region of interest (ROI)
      placed on each tumor with focal uptake. RESULTS: Acetate showed uptake in each
      HCC lesion when the animals were either fasted or fed with no significant
      difference in SUV values (p=0.177); some of the tumors were histologically
      confirmed as well-differentiated HCC while others were confirmed as moderately-
      or poorly-differentiated HCC; no focal uptake was found in the control animal.
      For the accompanying FDG scans, the uptake was detected only in animals that were
      fasted although the uptake pattern was different from that with acetate.
      CONCLUSION: This study provided a hint that fasting or not has little impact on
      PET imaging of HCC with acetate. It also confirmed prior finding regarding tumor
      heterogeneity that led to different tracer uptake pattern in the same tumor.
      Human studies are needed to validate the findings from this pre-clinical
      investigation.

PMID- 24683498
TI  - Estimation of Soft Tissue Mechanical Parameters from Robotic Manipulation Data.
AB  - Robotic motion planning algorithms used for task automation in robotic surgical
      systems rely on availability of accurate models of target soft tissue's
      deformation. Relying on generic tissue parameters in constructing the tissue
      deformation models is problematic; because, biological tissues are known to have
      very large (inter- and intra-subject) variability. A priori mechanical
      characterization (e.g., uniaxial bench test) of the target tissues before a
      surgical procedure is also not usually practical. In this paper, a method for
      estimating mechanical parameters of soft tissue from sensory data collected
      during robotic surgical manipulation is presented. The method uses force data
      collected from a multiaxial force sensor mounted on the robotic manipulator, and
      tissue deformation data collected from a stereo camera system. The tissue
      parameters are then estimated using an inverse finite element method. The effects
      of measurement and modeling uncertainties on the proposed method are analyzed in
      simulation. The results of experimental evaluation of the method are also
      presented.

PMID- 24683499
TI  - Modeling of Needle-Tissue Interaction Forces During Surgical Suturing.
AB  - This paper presents a model of needle tissue interaction forces that a rigid
      suture needle experiences during surgical suturing. The needle-tissue interaction
      forces are modeled as the sum of lumped parameters. The model has three main
      components; friction, tissue compression, and cutting forces. The tissue
      compression force uses the area that the needle sweeps out during a suture to
      estimate both the force magnitude and force direction. The area that the needle
      sweeps out is a direct result of driving the needle in a way that does not follow
      the natural curve of the needle. The friction force is approximated as a static
      friction force along the shaft of the needle. The cutting force acts only on the
      needle tip. The resulting force and torque model is experimentally validated
      using a tissue phantom. These results indicate that the proposed lumped parameter
      model is capable of accurately modeling the forces experienced during a suture.

PMID- 24683500
TI  - Needle Path Planning for Autonomous Robotic Surgical Suturing.
AB  - This paper develops a path plan for suture needles used with solid tissue volumes
      in endoscopic surgery. The path trajectory is based on the best practices that
      are used by surgeons. The path attempts to minimize the interaction forces
      between the tissue and the needle. Using surgical guides as a basis, two
      different techniques for driving a suture needle are developed. The two
      techniques are compared in hardware experiments by robotically driving the suture
      needle using both of the motion plans.

PMID- 24683501
TI  - Automated Pointing of Cardiac Imaging Catheters.
AB  - Intracardiac echocardiography (ICE) catheters enable high-quality ultrasound
      imaging within the heart, but their use in guiding procedures is limited due to
      the difficulty of manually pointing them at structures of interest. This paper
      presents the design and testing of a catheter steering model for robotic control
      of commercial ICE catheters. The four actuated degrees of freedom (4-DOF) are two
      catheter handle knobs to produce bi-directional bending in combination with
      rotation and translation of the handle. An extra degree of freedom in the system
      allows the imaging plane (dependent on orientation) to be directed at an object
      of interest. A closed form solution for forward and inverse kinematics enables
      control of the catheter tip position and the imaging plane orientation. The
      proposed algorithms were validated with a robotic test bed using electromagnetic
      sensor tracking of the catheter tip. The ability to automatically acquire imaging
      targets in the heart may improve the efficiency and effectiveness of intracardiac
      catheter interventions by allowing visualization of soft tissue structures that
      are not visible using standard fluoroscopic guidance. Although the system has
      been developed and tested for manipulating ICE catheters, the methods described
      here are applicable to any long thin tendon-driven tool (with single or bi
      directional bending) requiring accurate tip position and orientation control.

PMID- 24683502
TI  - Towards Clinically Optimized MRI-guided Surgical Manipulator for Minimally
      Invasive Prostate Percutaneous Interventions: Constructive Design.
AB  - This paper undertakes the modular design and development of a minimally invasive
      surgical manipulator for MRI-guided transperineal prostate interventions. Severe
      constraints for the MRI-compatibility to hold the minimum artifact on the image
      quality and dimensions restraint of the bore scanner shadow the design procedure.
      Regarding the constructive design, the manipulator kinematics has been optimized
      and the effective analytical needle workspace is developed and followed by
      proposing the workflow for the manual needle insertion. A study of the finite
      element analysis is established and utilized to improve the mechanism weaknesses
      under some inevitable external forces to ensure the minimum structure
      deformation. The procedure for attaching a sterile plastic drape on the robot
      manipulator is discussed. The introduced robotic manipulator herein is aimed for
      the clinically prostate biopsy and brachytherapy applications.

PMID- 24683503
TI  - Matching on Race and Ethnicity in Case-Control Studies as a Means of Control for
      Population Stratification.
AB  - Some investigators argue that controlling for self-reported race or ethnicity,
      either in statistical analysis or in study design, is sufficient to mitigate
      unwanted influence from population stratification. In this report, we evaluated
      the effectiveness of a study design involving matching on self-reported ethnicity
      and race in minimizing bias due to population stratification within an ethnically
      admixed population in California. We estimated individual genetic ancestry using
      structured association methods and a panel of ancestry informative markers, and
      observed no statistically significant difference in distribution of genetic
      ancestry between cases and controls (P=0.46). Stratification by Hispanic
      ethnicity showed similar results. We evaluated potential confounding by genetic
      ancestry after adjustment for race and ethnicity for 1260 candidate gene SNPs,
      and found no major impact (>10%) on risk estimates. In conclusion, we found no
      evidence of confounding of genetic risk estimates by population substructure
      using this matched design. Our study provides strong evidence supporting the race
      and ethnicity-matched case-control study design as an effective approach to
      minimizing systematic bias due to differences in genetic ancestry between cases
      and controls.

PMID- 24683504
TI  - Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance.
AB  - Nucleic acid therapeutics are attracting renewed interest due to recent clinical
      advances and product approvals. Most leading programs use chemical conjugates, or
      viral vectors in the case of gene therapy, while several use no delivery system
      at all. Polymer systems, which have been at the periphery of this renaissance,
      often involve greater molecular complexity than competing approaches, which must
      be justified by their advantages. Advanced analytical methods, along with
      biological tools for characterizing biotransformation and intracellular
      trafficking, are increasingly being applied to nucleic acid delivery systems
      including those based on polymers. These frontiers of investigation create the
      opportunity for an era where highly defined polymer compositions are optimized
      based on mechanistic insights in a way that has not been previously possible,
      offering the prospect of greater differentiation from alternatives. This will
      require integrated collaboration between polymer scientists and those from other
      disciplines.

PMID- 24683505
TI  - The role of FGF2 in spinal cord trauma and regeneration research.

PMID- 24683506
TI  - N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and
      therapeutic opportunities.
AB  - BACKGROUND: There is an expanding field of research investigating the benefits of
      medicines with multiple mechanisms of action across neurological disorders. N
      acetylcysteine (NAC), widely known as an antidote to acetaminophen overdose, is
      now emerging as treatment of vascular and nonvascular neurological disorders. NAC
      as a precursor to the antioxidant glutathione modulates glutamatergic,
      neurotrophic, and inflammatory pathways. AIM AND DISCUSSION: Most NAC studies up
      to date have been carried out in animal models of various neurological disorders
      with only a few studies completed in humans. In psychiatry, NAC has been tested
      in over 20 clinical trials as an adjunctive treatment; however, this topic is
      beyond the scope of this review. Herein, we discuss NAC molecular, intracellular,
      and systemic effects, focusing on its potential applications in neurodegenerative
      diseases including spinocerebellar ataxia, Parkinson's disease, tardive
      dyskinesia, myoclonus epilepsy of the Unverricht-Lundbor type as well as multiple
      sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. CONCLUSION:
      Finally, we review the potential applications of NAC to facilitate recovery after
      traumatic brain injury, cerebral ischemia, and in treatment of cerebrovascular
      vasospasm after subarachnoid hemorrhage.

PMID- 24683507
TI  - Multi-analyte profile analysis of plasma immune proteins: altered expression of
      peripheral immune factors is associated with neuropsychiatric symptom severity in
      adults with and without chronic hepatitis C virus infection.
AB  - BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)
      associated differences in the expression of 47 inflammatory factors and to
      evaluate the potential role of peripheral immune activation in HCV-associated
      neuropsychiatric symptoms-depression, anxiety, fatigue, and pain. An additional
      objective was to evaluate the role of immune factor dysregulation in the
      expression of specific neuropsychiatric symptoms to identify biomarkers that may
      be relevant to the treatment of these neuropsychiatric symptoms in adults with or
      without HCV. MethodsBlood samples and neuropsychiatric symptom severity scales
      were collected from HCV-infected adults (HCV+, n = 39) and demographically
      similar noninfected controls (HCV-, n = 40). Multi-analyte profile analysis was
      used to evaluate plasma biomarkers. ResultsCompared with HCV- controls, HCV+
      adults reported significantly (P < 0.050) greater depression, anxiety, fatigue,
      and pain, and they were more likely to present with an increased inflammatory
      profile as indicated by significantly higher plasma levels of 40% (19/47) of the
      factors assessed (21%, after correcting for multiple comparisons). Within the
      HCV+ group, but not within the HCV- group, an increased inflammatory profile
      (indicated by the number of immune factors > the LDC) significantly correlated
      with depression, anxiety, and pain. Within the total sample, neuropsychiatric
      symptom severity was significantly predicted by protein signatures consisting of
      4-10 plasma immune factors; protein signatures significantly accounted for 19-40%
      of the variance in depression, anxiety, fatigue, and pain. ConclusionsOverall,
      the results demonstrate that altered expression of a network of plasma immune
      factors contributes to neuropsychiatric symptom severity. These findings offer
      new biomarkers to potentially facilitate pharmacotherapeutic development and to
      increase our understanding of the molecular pathways associated with
      neuropsychiatric symptoms in adults with or without HCV. 

PMID- 24683508
TI  - Unilateral disruptions in the default network with aging in native space.
AB  - BACKGROUND: Disruption of the default-mode network (DMN) in healthy elders has
      been reported in many studies. METHODS: In a group of 51 participants (25 young,
      26 elder) we examined DMN connectivity in subjects' native space. In the native
      space method, subject-specific regional masks (obtained independently for each
      subject) are used to extract regional fMRI times series. This approach
      substitutes the spatial normalization and subsequent smoothing used in prevailing
      methods, affords more accurate spatial localization, and provides the power to
      examine connectivity separately in the two hemispheres instead of averaging
      regions across hemispheres. RESULTS: The native space method yielded new findings
      which were not detectable by the prevailing methods. The most reliable and robust
      disruption in elders' DMN connectivity were found between supramarginal gyrus and
      superior-frontal cortex in the right hemisphere only. The mean correlation
      between these two regions in young participants was about 0.5, and dropped
      significantly to 0.04 in elders (P = 2.1 * 10(-5)). In addition, the magnitude of
      functional connectivity between these regions in the right hemisphere correlated
      with memory (P = 0.05) and general fluid ability (P = 0.01) in elder participants
      and with speed of processing in young participants (P = 0.008). These
      relationships were not observed in the left hemisphere. CONCLUSION: These
      findings suggest that analysis of DMN connectivity in subjects' native space can
      improve localization and power and that it is important to examine connectivity
      separately in each hemisphere.

PMID- 24683510
TI  - Brain training: rationale, methods, and pilot data for a specific
      visuomotor/visuospatial activity program to change progressive cognitive decline.
AB  - INTRODUCTION: Research in the field of the aging brain has evolved to the extent
      that it is now commonly understood that actively engaging in cognitive tasks
      provides the potential of being beneficial in affecting the trajectory of age
      related cognitive decline. What remains to be examined is the extent, and type,
      of program required to effect change in aging cognitively impaired individuals.
      METHODS: To address this issue, a cognitive program focusing on the use of
      visuospatial (VS)/visuomotor (VM) elements was applied to a group of six older
      individuals with identified progressive cognitive impairments. It was
      hypothesized that using tasks with VS and VM components may be beneficial in
      supporting overall brain performance, and subsequently assist individuals to
      perform well in various cognitive and behavioral tasks. RESULTS: Results showed
      that on many evaluative measures individuals remained stable, or improved in
      performance with medium-to-large effect sizes (e.g., 0.3-1.0). Thus, in a
      cognitively impaired population sample where decline would be the norm, our
      participants improved or remained stable. CONCLUSION: The novel application of a
      VS/VM training program shows promise in addressing global cognitive decline, by
      targeting a brain area susceptible to early disruptions and providing it with
      additional and ongoing stimulative tasks in an effort to bolster its functioning
      and subsequently overall brain functioning.

PMID- 24683511
TI  - Neural differences in processing of case particles in Japanese: an fMRI study.
AB  - INTRODUCTION: In subject-object-verb (SOV) languages, such as Japanese, sentence
      processing proceeds incrementally to the late presentation of the head (verb).
      Japanese case particles play a crucial role in sentence processing; however,
      little is known about how these particles are processed. In particular, it is
      still unclear how the functional difference between case particles is represented
      in the human brain. METHODS: In this study, we conducted an fMRI experiment using
      an event-related design to directly compare brain activity during Japanese case
      particle processing among the nominative case ga, accusative case o, and dative
      case ni. Twenty five native Japanese speakers were asked to judge whether the
      presented character was a particle in a particle judgment task and whether the
      character ended with a specific vowel in a phonological judgment task, which was
      used as a control condition. RESULTS: A particle comparison demonstrated that the
      processing of ni was associated with significantly weaker brain activity than
      that of ga and o in the left middle frontal gyrus (MFG) and the inferior frontal
      gyrus (IFG). Significantly greater brain activity associated with ni relative to
      ga in the right IFG was also observed. CONCLUSION: These results suggest that the
      Japanese case particles ga, ni, and o are represented differently in the brain.

PMID- 24683509
TI  - White matter integrity is associated with alcohol cue reactivity in heavy
      drinkers.
AB  - Neuroimaging studies have shown that white matter damage accompanies excessive
      alcohol use, but the functional correlates of alcohol-related white matter
      disruption remain unknown. This study applied tract-based spatial statistics
      (TBSS) to diffusion tensor imaging (DTI) data from 332 heavy drinkers (mean age =
      31.2 +/- 9.4; 31% female) to obtain averaged fractional anisotropy (FA) values of
      18 white matter tracts. Statistical analyses examined correlations of FA values
      with blood-oxygenation-level-dependent (BOLD) response to an alcohol taste cue,
      measured with functional magnetic resonance imaging (fMRI). FA values of nine
      white matter tracts (anterior corona radiata, body of corpus callosum, cingulate
      gyrus, external capsule, fornix, inferior frontooccipital fasciculus, posterior
      corona radiata, retrolenticular limb of internal capsule, and superior
      longitudinal fasciculus) were significantly, negatively correlated with BOLD
      activation in medial frontal gyrus, parahippocampal gyrus, fusiform gyrus,
      cingulum, thalamus, caudate, putamen, insula, and cerebellum. The inverse
      relation between white matter integrity and functional activation during the
      alcohol taste cue provides support for the hypothesis that lower white matter
      integrity in frontoparietal and corticolimbic networks is a factor in loss of
      control over alcohol consumption. 

PMID- 24683512
TI  - Fgf2 improves functional recovery-decreasing gliosis and increasing radial glia
      and neural progenitor cells after spinal cord injury.
AB  - OBJECTIVES: A major impediment for recovery after mammalian spinal cord injury
      (SCI) is the glial scar formed by proliferating reactive astrocytes. Finding
      factors that may reduce glial scarring, increase neuronal survival, and promote
      neurite outgrowth are of major importance for improving the outcome after SCI.
      Exogenous fibroblast growth factor (Fgf) has been shown to decrease injury volume
      and improve functional outcome; however, the mechanisms by which this is mediated
      are still largely unknown. METHODS: In this study, Fgf2 was administered for 2
      weeks in mice subcutaneously, starting 30 min after spinal cord hemisection.
      RESULTS: Fgf2 treatment decreased the expression of TNF-a at the lesion site,
      decreased monocyte/macrophage infiltration, and decreased gliosis. Fgf2 induced
      astrocytes to adopt a polarized morphology and increased expression of radial
      markers such as Pax6 and nestin. In addition, the levels of chondroitin sulfate
      proteoglycans (CSPGs), expressed by glia, were markedly decreased. Furthermore,
      Fgf2 treatment promotes the formation of parallel glial processes, "bridges," at
      the lesion site that enable regenerating axons through the injury site.
      Additionally, Fgf2 treatment increased Sox2-expressing cells in the gray matter
      and neurogenesis around and at the lesion site. Importantly, these effects were
      correlated with enhanced functional recovery of the left paretic hind limb.
      CONCLUSIONS: Thus, early pharmacological intervention with Fgf2 following SCI is
      neuroprotective and creates a proregenerative environment by the modulation of
      the glia response.

PMID- 24683513
TI  - Neural substrates of socioemotional self-awareness in neurodegenerative disease.
AB  - BACKGROUND: Neuroimaging studies examining neural substrates of impaired self
      awareness in patients with neurodegenerative diseases have shown divergent
      results depending on the modality (cognitive, emotional, behavioral) of
      awareness. Evidence is accumulating to suggest that self-awareness arises from a
      combination of modality-specific and large-scale supramodal neural networks.
      METHODS: We investigated the structural substrates of patients' tendency to
      overestimate or underestimate their own capacity to demonstrate empathic concern
      for others. Subjects' level of empathic concern was measured using the
      Interpersonal Reactivity Index, and subject-informant discrepancy scores were
      used to predict regional atrophy pattern, using voxel-based morphometry analysis.
      Of the 102 subjects, 83 were patients with neurodegenerative diseases such as
      behavioral variant frontotemporal dementia (bvFTD) or semantic variant primary
      progressive aphasia (svPPA); the other 19 were healthy older adults. RESULTS:
      bvFTD and svPPA patients typically overestimated their level of empathic concern
      compared to controls, and overestimating one's empathic concern predicted damage
      to predominantly right-hemispheric anterior infero-lateral temporal regions,
      whereas underestimating one's empathic concern showed no neuroanatomical basis.
      CONCLUSIONS: These findings suggest that overestimation and underestimation of
      one's capacity for empathic concern cannot be interpreted as varying degrees of
      the same phenomenon, but may arise from different pathophysiological processes.
      Damage to anterior infero-lateral temporal regions has been associated with
      semantic self-knowledge, emotion processing, and social perspective taking;
      neuropsychological functions partly associated with empathic concern itself.
      These findings support the hypothesis that-at least in the socioemotional domain
      neural substrates of self-awareness are partly modality-specific.

PMID- 24683514
TI  - A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber
      tract anomalies in healthy young subjects.
AB  - BACKGROUND: Changes in fiber tract architecture have gained attention as a
      potentially important aspect of schizophrenia neuropathology. Although the exact
      pathogenesis of these abnormalities yet remains to be elucidated, a genetic
      component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated
      schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1
      rs35753505 variant on white matter structure in healthy young individuals with no
      family history of psychosis. METHODS: We compared fractional anisotropy in 54
      subjects that were either homozygous for the risk C allele carriers (n = 31) for
      rs35753505 or homozygous for the T allele (n = 23) using diffusion tensor imaging
      with 3T. Tract-Based Spatial Statistics (TBSS), a method especially developed for
      diffusion data analysis, was used to improve white matter registration and to
      focus the statistical analysis to major fiber tracts. RESULTS: Statistical
      analysis showed that homozygous risk C allele carriers featured elevated
      fractional anisotropy (FA) in the right perihippocampal region and the white
      matter proximate to the left area 4p as well as the right hemisphere of the
      cerebellum. We found three clusters of reduced FA values in homozygous C allele
      carriers: in the left superior parietal region, the right prefrontal white matter
      and in the deep white matter of the left frontal lobe. CONCLUSION: Our results
      highlight the importance of Neuregulin-1 for structural connectivity of the right
      medial temporal lobe. This finding is in line with well known neuropathological
      findings in this region in patients with schizophrenia.

PMID- 24683515
TI  - Functional MRI mapping of visual function and selective attention for performance
      assessment and presurgical planning using conjunctive visual search.
AB  - BACKGROUND: Accurate mapping of visual function and selective attention using
      fMRI is important in the study of human performance as well as in presurgical
      treatment planning of lesions in or near visual centers of the brain. Conjunctive
      visual search (CVS) is a useful tool for mapping visual function during fMRI
      because of its greater activation extent compared with high-capacity parallel
      search processes. AIMS: The purpose of this work was to develop and evaluate a
      CVS that was capable of generating consistent activation in the basic and higher
      level visual areas of the brain by using a high number of distractors as well as
      an optimized contrast condition. MATERIALS AND METHODS: Images from 10 healthy
      volunteers were analyzed and brain regions of greatest activation and
      deactivation were determined using a nonbiased decomposition of the results at
      the hemisphere, lobe, and gyrus levels. The results were quantified in terms of
      activation and deactivation extent and mean z-statistic. RESULTS: The proposed
      CVS was found to generate robust activation of the occipital lobe, as well as
      regions in the middle frontal gyrus associated with coordinating eye movements
      and in regions of the insula associated with task-level control and focal
      attention. As expected, the task demonstrated deactivation patterns commonly
      implicated in the default-mode network. Further deactivation was noted in the
      posterior region of the cerebellum, most likely associated with the formation of
      optimal search strategy. CONCLUSION: We believe the task will be useful in
      studies of visual and selective attention in the neuroscience community as well
      as in mapping visual function in clinical fMRI.

PMID- 24683516
TI  - Enhanced cardiac perception predicts impaired performance in the Iowa Gambling
      Task in patients with panic disorder.
AB  - OBJECTIVE: Somatic marker theory predicts that somatic cues serve intuitive
      decision making; however, cardiovascular symptoms are threat cues for patients
      with panic disorder (PD). Therefore, enhanced cardiac perception may aid
      intuitive decision making only in healthy individuals, but impair intuitive
      decision making in PD patients. METHODS: PD patients and age-and sex-matched
      volunteers without a psychiatric diagnosis (n = 17, respectively) completed the
      Iowa Gambling Task (IGT) as a measure of intuitive decision making.
      Interindividual differences in cardiac perception were assessed with a common
      mental-tracking task. RESULTS: In line with our hypothesis, we found a pattern of
      opposing associations (Fisher's Z = 1.78, P = 0.04) of high cardiac perception
      with improved IGT-performance in matched control-participants (r = 0.36, n = 14)
      but impaired IGT-performance in PD patients (r = -0.38, n = 13). CONCLUSION:
      Interoceptive skills, typically assumed to aid intuitive decision making, can
      have the opposite effect in PD patients who experience interoceptive cues as
      threatening, and tend to avoid them. This may explain why PD patients frequently
      have problems with decision making in everyday life. Screening of cardiac
      perception may help identifying patients who benefit from specifically tailored
      interventions.

PMID- 24683517
TI  - The attentional-relevance and temporal dynamics of visual-tactile crossmodal
      interactions differentially influence early stages of somatosensory processing.
AB  - BACKGROUND: Crossmodal interactions between relevant visual and tactile inputs
      can enhance attentional modulation at early stages in somatosensory cortices to
      achieve goal-oriented behaviors. However, the specific contribution of each
      sensory system during attentional processing remains unclear. We used EEG to
      investigate the effects of visual priming and attentional relevance in modulating
      somatosensory cortical responses. METHODS: Healthy adults performed a sensory
      integration task that required scaled motor responses dependent on the amplitudes
      of tactile and visual stimuli. Participants completed an attentional paradigm
      comprised of 5 conditions that presented sequential or concurrent pairs of
      discrete stimuli with random amplitude variations: 1) tactile-tactile (TT), 2)
      visual-visual (VV), 3) visual-tactile simultaneous (SIM), 4) tactile-visual delay
      (TVd), and 5) visual-tactile delay (VTd), each with a 100 ms temporal delay
      between stimulus onsets. Attention was directed to crossmodal conditions and
      graded motor responses representing the summation of the 2 stimulus amplitudes
      were made. RESULTS: Results of somatosensory ERPs showed that the modality
      specific components (P50, P100) were sensitive to i) the temporal dynamics of
      crossmodal interactions, and ii) the relevance of these sensory signals for
      behaviour. CONCLUSION: Notably, the P50 amplitude was greatest in the VTd
      condition, suggesting that presentation of relevant visual information for
      upcoming movement modulates somatosensory processing in modality-specific
      cortical regions, as early as the primary somatosensory cortex (SI).

PMID- 24683519
TI  - Pavlovian-conditioned alcohol-seeking behavior in rats is invigorated by the
      interaction between discrete and contextual alcohol cues: implications for
      relapse.
AB  - INTRODUCTION: Drug craving can be independently stimulated by cues that are
      directly associated with drug intake (discrete drug cues), as well as by
      environmental contexts in which drug use occurs (contextual drug cues). We tested
      the hypothesis that the context in which a discrete alcohol-predictive cue is
      experienced can influence how robustly that cue stimulates alcohol-seeking
      behavior. METHODS: Male, Long-Evans rats received Pavlovian discrimination
      training (PDT) sessions in which one conditioned stimulus (CS+; 16
      trials/session) was paired with ethanol (0.2 mL/CS+) and a second stimulus (CS-;
      16 trials/session) was not. PDT occurred in a specific context, and entries into
      a fluid port where ethanol was delivered were measured during each CS. Next, rats
      were acclimated to an alternate (nonalcohol) context where cues and ethanol were
      withheld. Responses to the nonextinguished CS+ and CS- were then tested without
      ethanol in the alcohol-associated PDT context, the nonalcohol context or a third,
      novel context. RESULTS: Across PDT the CS+ elicited more port entries than the CS
      , indicative of Pavlovian discrimination learning. At test, the CS+ elicited more
      port entries than the CS- in all three contexts: however, alcohol seeking driven
      by the CS+ was more robust in the alcohol-associated context. In a separate
      experiment, extinguishing the context-alcohol association did not influence
      subsequent CS+ responding but reduced alcohol seeking during non-CS+ intervals
      during a spontaneous recovery test. CONCLUSION: These results indicate that
      alcohol-seeking behavior driven by a discrete Pavlovian alcohol cue is strongly
      invigorated by an alcohol context, and suggest that contexts may function as
      excitatory Pavlovian conditioned stimuli that directly trigger alcohol-seeking
      behavior.

PMID- 24683518
TI  - Brain microstructural changes and cognitive correlates in patients with pure
      obsessive compulsive disorder.
AB  - OBJECT: The aim of this study was to investigate macrostructural and
      microstructural brain changes in patients with pure obsessive compulsive disorder
      (OCD) and to examine the relationship between brain structure and
      neuropsychological deficits. METHOD: 20 patients with OCD underwent a
      comprehensive neuropsychological battery. A combined voxel-based morphometry
      (VBM) and diffusion tensor imaging (DTI) analysis was used to capture gray matter
      (GM) and white matter changes in OCD patients as compared to pair-matched healthy
      volunteers. Multiple regression designs explored the relationship between
      cognition and neuroimaging parameters. RESULTS: OCD patients had increased mean
      diffusivity (MD) in GM nodes of the orbitofronto-striatal loop (left dorsal
      anterior cingulate [Z = 3.67, P < 0.001] left insula [Z = 3.35 P < 0.001] left
      thalamus [Z = 3.59, P < 0.001] left parahippocampal gyrus [Z = 3.77 P < 0.001])
      and in lateral frontal and posterior associative cortices (right frontal
      operculum [Z = 3.42 P < 0.001], right temporal lobe [Z = 3.79 P < 0.001] left
      parietal lobe [Z = 3.91 P < 0.001]). Decreased fractional anisotropy (FA) was
      detected in intrahemispheric (left superior longitudinal fasciculus [Z = 4.07 P <
      0.001]) and interhemispheric (body of corpus callosum [CC, Z = 4.42 P < 0.001])
      bundles. Concurrently, the semantic fluency score, a measure of executive control
      processes, significantly predicted OCD diagnosis (Odds Ratio = 1.37; 95%
      Confidence Intervals = 1.09-1.73; P = 0.0058), while variation in performance was
      correlated with increased MD in left temporal (Z = 4.25 P < 0.001) and bilateral
      parietal regions (left Z = 3.94, right Z = 4.19 P < 0.001), and decreased FA in
      the right posterior corona radiata (Z = 4.07 P < 0.001) and the left
      corticospinal tract (Z = 3.95 P < 0.001). CONCLUSIONS: The reported deficit in
      executive processes and the underlying microstructural alterations may qualify as
      behavioral and biological markers of OCD.

PMID- 24683520
TI  - BDNF Met66 modulates the cumulative effect of psychosocial childhood adversities
      on major depression in adolescents.
AB  - BACKGROUND: The interplay among lifetime adversities and the genetic background
      has been previously examined on a variety of measures of depression; however,
      only few studies have focused on major depression disorder (MDD) in adolescence.
      METHODS: Using clinical data and DNA samples from mouthwash gathered from an
      epidemiological study on the prevalence of mental disorders in youths between 12
      and 17 years old, we tested the statistical interaction between a set of
      psychosocial adversities experienced during childhood (CAs) with two common
      polymorphisms in the brain-derived neurotrophic factor (BDNF) (Val66Met) and
      SLC6A4 (L/S) genes on the probability of suffering MDD in adolescence. RESULTS:
      Genotype or allele frequencies for both polymorphisms were similar between groups
      of comparison (MDD N = 246; controls N = 270). The CAs factors: Abuse, neglect,
      and family dysfunctions; parental maladjustment, parental death, and to have
      experienced a life-threatening physical illness were predictors of clinical
      depression in adolescents. Remarkably, the cumulative number of psychosocial
      adversities was distinctly associated with an increase in the prevalence of
      depression but only in those Val/Val BDNF individuals; while the possession of at
      least a copy of the BDNF Met allele (i.e., Met +) was statistically linked with a
      "refractory" or resilient phenotype to the noticeable influence of CAs.
      CONCLUSION: Liability or resilience to develop MDD in adolescence is dependent of
      a complex interplay between particular environmental exposures and a set of
      plasticity genes including BDNF. A better understanding of these factors is
      important for developing better prevention and early intervention measures.

PMID- 24683521
TI  - Genome-wide polygenic scoring for a 14-year long-term average depression
      phenotype.
AB  - BACKGROUND: Despite moderate heritability estimates for depression-related
      phenotypes, few robust genetic predictors have been identified. Potential
      explanations for this discrepancy include the use of phenotypic measures taken
      from a single time point, rather than integrating information over longer time
      periods via multiple assessments, and the possibility that genetic risk is shaped
      by multiple loci with small effects. METHODS: We developed a 14-year long-term
      average depression measure based on 14 years of follow-up in the Nurses' Health
      Study (NHS; N = 6989 women). We estimated polygenic scores (PS) with internal
      whole-genome scoring (NHS-GWAS-PS). We also constructed PS by applying two
      external PS weighting algorithms from independent samples, one previously shown
      to predict depression (GAIN-MDD-PS) and another from the largest genome-wide
      analysis currently available (PGC-MDD-PS). We assessed the association of all
      three PS with our long-term average depression phenotype using linear, logistic,
      and quantile regressions. RESULTS: In this study, the three PS approaches
      explained at most 0.2% of variance in the long-term average phenotype. Quantile
      regressions indicated PS had larger impacts at higher quantiles of depressive
      symptoms. Quantile regression coefficients at the 75th percentile were at least
      40% larger than at the 25th percentile in all three polygenic scoring algorithms.
      The interquartile range comparison suggested the effects of PS significantly
      differed at the 25th and 75th percentiles of the long-term depressive phenotype
      for the PGC-MDD-PS (P = 0.03), and this difference also reached borderline
      statistical significance for the GAIN-MDD-PS (P = 0.05). CONCLUSIONS: Integrating
      multiple phenotype assessments spanning 14 years and applying different polygenic
      scoring approaches did not substantially improve genetic prediction of
      depression. Quantile regressions suggested the effects of PS may be largest at
      high quantiles of depressive symptom scores, presumably among people with
      additional, unobserved sources of vulnerability to depression.

PMID- 24683522
TI  - First use of (18)F-labeled ML-10 PET to assess apoptosis change in a newly
      diagnosed glioblastoma multiforme patient before and early after therapy.
AB  - OBJECTIVES: The authors present the first use of the novel positron emission
      tomography (PET) apoptosis tracer (18)F-labeled 2-(5-fluoro-pentyl)-2-methyl
      malonic acid ((18)F-ML-10) for early-therapy response assessment of a newly
      diagnosed glioblastoma multiforme (GBM) patient. CASE REPORT: A 71-year-old male
      with a newly diagnosed GBM received (18)F-ML-10 PET scans prior to therapy
      initiation (baseline) and after completing 3 weeks of whole-brain radiation
      therapy with concomitant temozolomide chemotherapy (early-therapy assessment,
      ETA). The baseline (18)F-ML-10 PET scan showed increased tracer uptake at the
      site of the GBM, with highest activity toward the central portion of the tumor.
      At the ETA time point, a new distribution of tracer uptake was observed compared
      to baseline. Normalized pixel-by-pixel subtraction of baseline from ETA was used
      to quantify change in tracer distribution between (18)F-ML-10 PET imaging time
      points. Results of this analysis showed reduction in (18)F-ML-10 uptake at the
      site of greatest baseline uptake, but increased uptake around the periphery of
      the tumor at the early-therapy time point. CONCLUSION: The changing patterns of
      (18)F-ML-10 uptake between baseline and ETA are suggestive for therapy-induced
      tumor cellular apoptosis.

PMID- 24683525
TI  - Simulated clients reveal programmatic factors that may influence contraceptive
      use in Kisumu, Kenya.
AB  - A better understanding of the factors influencing use of family planning has the
      potential to increase contraceptive prevalence and improve the ability of women
      and their partners to freely choose the number and spacing of their children.
      Investigations into factors contributing to unmet need frequently rely on data
      collected using household surveys or interviews with family planning clients and
      providers. This research utilizes qualitative information resulting from
      simulated client visits to investigate programmatic barriers to contraceptive use
      in a sample of 19 health care facilities in Kisumu East District, a city in
      Western Kenya. Simulated client reports indicate deficiencies in provider
      competence as well as tenuous relations between providers and clients. In
      addition, simulated client data reveal occasional absences of providers during
      normal facility hours of operation and requests of informal fees for services.
      Trainings that address specific gaps in provider medical knowledge and counseling
      skills as well as client-provider relations may reduce programmatic barriers to
      contraceptive use. In addition, improved supervision and oversight at facilities
      may increase physical and financial access to services. Future research
      investigating provider motivations may illuminate root causes of programmatic
      barriers.

PMID- 24683524
TI  - Sodium MR Imaging of Articular Cartilage Pathologies.
AB  - Many studies have proved that noninvasive sodium MR imaging can directly
      determine the cartilage GAG content, which plays a central role in cartilage
      homeostasis. New technical developments in the recent decade have helped to
      transfer this method from in vitro to pre-clinical in vivo studies. Sodium
      imaging has already been applied for the evaluation of cartilage and repair
      tissue in patients after various cartilage repair surgery techniques and in
      patients with osteoarthritis. These studies showed that this technique could be
      helpful not only for assessment of the cartilage status, but also predictive for
      osteoarthritis. However, due to the low detectable sodium MR signal in cartilage,
      sodium imaging is still challenging, and further hardware and software
      improvements are necessary for translating sodium MR imaging into clinical
      practice, preferably to 3T MR systems.

PMID- 24683527
TI  - Activity of hypertonic solution with Silver and Potassium Sucrose Octasulfate on
      nasal symptoms in obstructive rhinopathy with and without rhinosinusitis.
AB  - BACKGROUND: Nasal obstruction is a primary symptom of common upper respiratory
      tract disorders. In clinical practice nasal saline solutions are recommended for
      the cleansing of nasal cavities and relieving nasal symptoms. METHODS: 55
      patients (aged 25-70 years) suffering from obstructive rhinopathy, with nasal
      obstruction/congestion of moderate severity persistent since at least 10 days in
      advance of recruitment with/without rhinosinusitis was randomly treated with an
      hypertonic solution composed by Silver Sucrose Octasulfate and Potassium Sucrose
      Octasulfate (SILSOS) or isotonic solution for 20 days. At baseline (T0), ten days
      (T10) and twenty days (T20) after SILSOS treatment, study participants were
      evaluated subjectively with VAS and SNOT-22, objectively by Active Anterior
      Rhinomanometry (AAR) and MCC/MCTt determination. Forty-four patients were
      followed-up 30 days after the end of treatment by a phone interview. RESULTS: The
      AAR analysis showed in SILSOS group a significantly (p < 0.05) ameliorated in
      expiratory flow, at T0-T10 and T0-T20. No improvement in MCTt was observed over
      the 20 days study period. The mean values MCC of significantly improved at T20 (p
      < 0.05). VAS total score showed improvement along all time-intervals. Nasal
      obstruction was back 30 days after the end of treatment with SILSOS in only 3
      patients and reported to be in a mild form. CONCLUSIONS: The obtained results
      show that SILSOS hyper has added to the mechanical action of removal of
      secretions a specific decongestant and antiseptic effect lasting longer after the
      end of treatment. Could help to fluidize thick mucus, improve respiration and
      promote resolution of symptoms, preventing pathogens adhesion to nasal mucosa.

PMID- 24683526
TI  - L-type Ca2+ channels in heart and brain.
AB  - L-type calcium channels (Cav1) represent one of the three major classes (Cav1-3)
      of voltage-gated calcium channels. They were identified as the target of
      clinically used calcium channel blockers (CCBs; so-called calcium antagonists)
      and were the first class accessible to biochemical characterization. Four of the
      10 known alpha1 subunits (Cav1.1-Cav1.4) form the pore of L-type calcium channels
      (LTCCs) and contain the high-affinity drug-binding sites for dihydropyridines and
      other chemical classes of organic CCBs. In essentially all electrically excitable
      cells one or more of these LTCC isoforms is expressed, and therefore it is not
      surprising that many body functions including muscle, brain, endocrine, and
      sensory function depend on proper LTCC activity. Gene knockouts and inherited
      human diseases have allowed detailed insight into the physiological and
      pathophysiological role of these channels. Genome-wide association studies and
      analysis of human genomes are currently providing even more hints that even small
      changes of channel expression or activity may be associated with disease, such as
      psychiatric disease or cardiac arrhythmias. Therefore, it is important to
      understand the structure-function relationship of LTCC isoforms, their
      differential contribution to physiological function, as well as their fine-tuning
      by modulatory cellular processes.

PMID- 24683528
TI  - Expression of phosphodiesterase 6 (PDE6) in human breast cancer cells.
AB  - Considerable epidemiological evidence demonstrates a positive association between
      artificial light at night (LAN) levels and incidence rates of breast cancer,
      suggesting that exposure to LAN is a risk factor for breast cancer. There is a 30
      50% higher risk of breast cancer in the highest LAN exposed countries compared to
      the lowest LAN countries, and studies showing higher incidence of breast cancer
      among shift workers exposed to more LAN have led the International Agency for
      Research on Cancer to classify shift work as a probable human carcinogen.
      Nevertheless, the means by which light can affect breast cancer is still unknown.
      In this study we examined established human breast cancer cell lines and
      patients' primary breast cancer tissues for expression of genetic components of
      phosphodiesterase 6 (PDE6), a cGMP-specific PDE involved in transduction of the
      light signal, and previously thought to be selectively expressed in
      photoreceptors. By microarray analysis we find highly significant expression of
      mRNA for the PDE6B, PDE6C, and PDE6D genes in both the cell lines and patients'
      tissues, minimal expression of PDE6A and PDE6G and no expression of PDE6H. Using
      antibody specific for PDE6beta, we find expression of PDE6B protein in a wide
      range of patients' tissues by immunohistochemistry, and in MCF-7 breast cancer
      cells by immunofluorescence and Western blot analysis. Considerable expression of
      key circadian genes, PERIOD 2, CLOCK, TIMELESS, CRYPTOCHROME 1, and CRYPTOCHROME
      2 was also seen in all breast cancer cell lines and all patients' breast cancer
      tissues. These studies indicate that genes for PDE6 and control of circadian
      rhythm are expressed in human breast cancer cells and tissues and may play a role
      in transducing the effects of light on breast cancer. 

PMID- 24683529
TI  - Effect of an exercise training intervention with resistance bands on blood cell
      counts during chemotherapy for lung cancer: a pilot randomized controlled trial.
AB  - PURPOSE: Chemotherapy for lung cancer can have a detrimental effect on white
      blood cell (WBC) and red blood cell (RBC) counts. Physical exercise may have a
      role in improving WBCs and RBCs, although few studies have examined cancer
      patients receiving adjuvant therapies. The purpose of this pilot trial was to
      examine the effects of an exercise intervention utilizing resistance bands on
      WBCs and RBCs in lung cancer patients receiving curative intent chemotherapy.
      METHODS: A sample of lung cancer patients scheduled for curative intent
      chemotherapy was randomly assigned to the exercise intervention (EX) condition or
      usual care (UC) condition. The EX condition participated in a three times weekly
      exercise program using resistance bands for the duration of chemotherapy.
      RESULTS: A total of 14 lung cancer patients completed the trial. EX condition
      participants completed 79% of planned exercise sessions. The EX condition was
      able to maintain WBCs over the course of the intervention compared to declines in
      the UC condition (p = .008; d = 1.68). There were no significant differences in
      change scores in RBCs. CONCLUSIONS: Exercise with resistance bands may help
      attenuate declines in WBCs in lung cancer patients receiving curative intent
      chemotherapy. Larger trials are warranted to validate these findings. Ultimately
      these findings could be informative for the development of supportive care
      strategies for lung cancer patients receiving chemotherapy. TRIAL REGISTRATION:
      Clinical Trials Registration #: NCT01130714.

PMID- 24683530
TI  - Painful plantar heel spur treatment with Co-60 teletherapy: factors influencing
      treatment outcome.
AB  - BACKGROUND: Painful plantar heel spur (PPHS) is a benign disorder with painful
      heels as a result of plantar calcaneal bone spur. Exact etiological factors are
      still unclear. Treatment typically consists of osteoarthritis tretment schedules
      and surgical techniques. External radiotherapy is another treatment option. This
      study is aimed to determine effectiveness and treatment outcomes of external
      radiotherapy in patients with PPHS. METHODS: Sixty-two patients with PPHS were
      analysed for radiotherapy success and other possible prognostic factors. All
      patients were treated with Co-60 units from parallel opposed lateral portals, to
      a total dose of 8 Gy. Responses to radiotherapy was assessed by visual analogue
      scale (VAS) of pain. Follow-up completed in December 2012 with 28 months median
      duration (range 22 to 35 months). Age, sex, patient number, spur settlement site,
      prior treatments, time interval between diagnosis and radiotherapy, pain scores
      (before and after radiotherapy), plantar fat-pillow thickness (PFPT; thickness of
      the plantar fat pad) and Bohler's angle estimations were analysed. RESULTS: Study
      included 53 female and 9 male patients with median age 57 (range 43-70). Time
      interval between PPHS diagnosis and radiotherapy were median 33 months (range10
      60). Radiotherapy response time interval were 6 months (range 3-10 months).
      Responses to radiotherapy were no response in 13 patients (21%), partial response
      in 13 patients (21%)- pain relief below 50% and complete response - no pain in 36
      patients (58%) respectively. Median PFPT of patients were 3.5 cm (range 1.20-4.50
      cm). Complete response rate was statistically significant in patients whom PFPT
      is greater than 3.5 cm. The Bohler's angle range is about 20-40 deg. Complete
      response rates were higher in patients with degree of Bohler's Angle 30 and
      below. CONCLUSIONS: Simplicity of treatment, lack of acute adverse effects and
      low cost, seem to make radiotherapy one of the safest, cheapest and also an
      effective treatment modality for PPHS.

PMID- 24683531
TI  - Ontogeny of the digestive system of the Octopus bimaculatus paralarvae (Verril,
      1883).
AB  - The high mortalities registered in the larval stage during octopus culturing are
      mainly due to nutritional deficiencies of the food provided. To understand the
      cause of this problem, we studied the ontogenetic development of the digestive
      system of Octopus bimaculatus paralarvae. An egg batch was obtained from a gravid
      female collected in the Bay of Los Angeles, Baja California, Mexico, and it was
      incubated in the laboratory during the summer of 2011. We observed that the
      formation of the digestive system began at 33 days post-laying (DPL). The newly
      hatched paralarvae had already formed the organs involved in food ingestion and
      digestion, although it was not possible to know accurately their degree of
      maturity. The present research constitutes the first description at the
      histological level of the ontogenic development of the digestive system of the O.
      bimaculatus paralarvae. This serves as a basis for future studies of the
      digestive physiology of this species. 

PMID- 24683532
TI  - DLC1 suppresses NF-kappaB activity in prostate cancer cells due to its
      stabilizing effect on adherens junctions.
AB  - DLC1 (Deleted in Liver Cancer 1) gene encodes a RhoGTPase-activating protein
      (RhoGAP), which exerts most of its tumor suppressor functions through suppression
      of small Rho GTPases proteins RhoA, RhoB, RhoC and to some degree Cdc42, but not
      Rac. RhoGTPases are implicated in NF-kappaB activation in highly invasive
      prostate carcinoma (PCA), with consequences on cell proliferation, survival and
      metastatic capacity. Here we demonstrate that DLC1 transduction in two androgen
      independent (AI) and highly metastatic PCA cell lines negatively regulates NF
      kappaB activity in a GAP- and alpha-catenin-dependent manner. Expressed DLC1
      protein suppresses the phosphorylation of NF-kappaB inhibitor, IkappaBalpha,
      causes its relocation from membrane ruffles into cytoplasm and attenuates its
      ubiquitination and subsequent degradation. DLC1-mediated NF-kB suppression and
      its effects are comparable to NF-kappaB inhibition using either shRNA knockdown
      or peptide inhibitor. Expression of transduced DLC1 suppressed the expression of
      NF-kappaB mediated genes. Such effects were found to be reliant on presence of
      calcium, indicating that the observed modifications are dependent on, and enabled
      by DLC-mediated stabilization of adherens junctions. These results expand the
      multitude of DLC1 interactions with other genes that modulate its oncosuppressive
      function, and may have potential therapeutic implications. 

PMID- 24683533
TI  - Effects of mutations and deletions in the human optineurin gene.
AB  - Optineurin is a gene associated with normal tension glaucoma (NTG) and
      amyotrophic lateral sclerosis (ALS). Foci formation and functional consequences
      including Golgi fragmentation, impairment of vesicle trafficking and apoptosis
      were observed previously upon overexpression and/or mutation of optineurin. In
      the current study, a total of 15 GFP tagged constructs that included NTG (E50K
      and 2 bp-AG insertion), ALS (exon 5 deletion, R96L, Q398X, and E478G) and non
      disease (L157A and D474N) associated mutants and a series of deletion fragments
      were cloned into mammalian expression vectors and transfected into RGC5 and/or
      Neuro2A cells to evaluate whether their expression confer the optineurin
      phenotypes. The cells were monitored for foci formation and stained by
      immunofluorescence with anti-GM130 to analyze the Golgi integrity. Transferrin
      uptake experiments were performed to evaluate the protein trafficking process and
      apoptosis was assessed with the active caspase 3/7 detection kit. We demonstrated
      that cells expressing E50K and R96L optineurin exhibited all of the optineurin
      phenotypes. Q398X mutant did not induce foci formation, but triggered Golgi
      fragmentation, impairment of transferrin uptake and increase in apoptosis. The 2
      bp-AG insertion mutant had a nuclear localization, compromised the transferrin
      uptake and strongly induced apoptosis. The foci formation, which might not
      predict the rest of the phenotypes, appeared to require both the leucine zipper
      and ubiquitin binding domains of the optineurin sequence. Interactions of
      optineurin with proteins including Rab8, myosin VI, huntingtin and transferrin
      receptor might directly determine whether the Golgi and protein trafficking
      phenotypes would be manifested. Examination of mutants and deletion fragments
      located at various sites of optineurin gene provide clues as to what regions of
      the gene may play a critical role in the development of pathologic consequences. 

PMID- 24683534
TI  - Free amino acid content in breast milk of adolescent and adult mothers in
      Ecuador.
AB  - Because of increased incidence of teenage births and high prevalence of lactation
      in Latin America, we determined the patterning of free amino acids (FAAs) in
      breast milk of 65 primiparous Ecuadorian women of varying ages (14-27 years). An
      automatic amino acid analyzer quantified levels of FAAs in milk samples obtained
      at three lactation stages: colostrum, transition, and mature milk. Regardless of
      mother's age, most FAAs increased with time postpartum, with taurine, glutamic
      acid, glutamine, and alanine being most abundant in all stages. 

PMID- 24683535
TI  - Monocular and binocular low-contrast visual acuity and optical coherence
      tomography in pediatric multiple sclerosis.
AB  - BACKGROUND: Low-contrast letter acuity and optical coherence tomography (OCT)
      capture visual dysfunction and axonal loss in adult-onset multiple sclerosis
      (MS), and have been proposed as secondary outcome metrics for therapeutic trials.
      Clinical trials will soon be launched in pediatric MS, but such outcome metrics
      have not been well-validated in this population. OBJECTIVES: To determine whether
      MS onset during childhood and adolescence is associated with measurable loss of
      visual acuity and thinning of the retinal nerve fiber layer (RNFL), whether such
      features are noted only in the context of clinical optic nerve inflammation
      (optic neuritis, ON) or are a feature of MS even in the absence of optic nerve
      relapses, and to define the optimal methods for such detection. STUDY DESIGN:
      Cross-sectional study. METHODS: Monocular and binocular high- and low-contrast
      letter acuity and contrast sensitivity were assessed in a cross-sectional cohort
      of children (ages 5 to 17 years) with MS (N=22 patients, 44 eyes; 8 patients with
      a history of ON) and disease-free controls (N=29 patients; 58 eyes) from three
      academic centers. Binocular summation was determined by calculating the number of
      letters correctly identified using the binocular score minus the better eye score
      for each visual test. RNFL thickness was measured using OCT (Stratus OCT-3).
      Results were analyzed in terms of "eyes" as: MS ON+, MS ON-, and control eyes.
      Generalized estimating equation (GEE) regression models were used to compare
      patients to controls. RESULTS: Traditional high-contrast visual acuity scores did
      not differ between MS ON+, MS ON-, and controls eyes. MS ON+ eyes had decreased
      monocular (p<0.001) and decreased binocular (p=0.007) low-contrast letter acuity
      (Sloan 1.25% contrast charts) scores. Monocular visual acuity did not differ when
      comparing MS ON- and control eyes. The magnitude of binocular summation using low
      contrast charts was similar for pediatric MS participants and controls and was
      not diminished in children with a history of ON. While the mean RNFL thickness
      for all MS eyes (103+/-17 MUm) trended lower when compared to corresponding
      measures in control eyes (109+/-9 MUm, p=0.085), we confirmed a highly
      significant reduction in mean RNFL thickness in MS eyes with a history of ON
      (86+/-22 MUm, p<0.001). RNFL thickness of MS ON- eyes in pediatric MS patients
      (109+/-11 MUm) did not differ from controls (p=0.994). CONCLUSIONS: Low-contrast
      letter acuity detects subtle visual loss in MS patients with prior ON, consistent
      with incomplete recovery, a finding further supported by RNFL loss in ON affected
      eyes. In MS patients with prior unilateral ON, binocular acuity is decreased;
      however, the magnitude of binocular summation is preserved, unlike adult-onset MS
      who exhibit a reduced capacity for visual compensation in the context of
      unilateral injury. Also unlike findings in adult-onset MS, we did not demonstrate
      RNFL thinning in ON- eyes of children and adolescents with MS. Further validation
      is required to confirm whether neurodegeneration of visual pathways occurs in the
      absence of relapse, and thus whether OCT will serve as a sensitive metric for
      such pathology in the pediatric and adolescent MS context.

PMID- 24683537
TI  - New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of
      coenzyme q10 in abating the detrimental outcomes.
AB  - OBJECTIVES: The present subacute study was designed to evaluate the effect of
      coenzyme Q 10 (CoQ10) in the 28 days aroclor 1254 exposure induced oxidative
      stress in mice brain. METHODS: Biochemical estimations of brain lipid
      peroxidation (LPO), reduced glutathione (GSH), and activities of superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and acetyl
      cholinesterase (AChE), and histopathological investigations of brain tissue were
      carried out. RESULTS: Oral exposure of aroclor 1254 (5 mg/kg) led to significant
      decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and
      increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg,
      intraperitoneal injection [IP]). This protection offered was comparable to that
      of L-deprenyl (1 mg/kg, IP) which served as a reference standard. CONCLUSIONS:
      Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and
      induces oxidative stress in the brains of Swiss albino mice. Supplementation of
      CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently
      enhanced acetyl cholinesterase activity which reflects its influence on the
      cholinergic system.

PMID- 24683536
TI  - Intestinal stem cell injury and protection during cancer therapy.
AB  - Radiation and chemotherapy remain the most effective and widely used cancer
      treatments. These treatments cause DNA damage and selectively target rapidly
      proliferating cells such as cancer cells, as well as inevitably cause damage to
      normal tissues, particularly those undergoing rapid self renewal. The side
      effects associated with radiation and chemotherapy are most pronounced in the
      hematopoietic (HP) system and gastrointestinal (GI) tract. These tissues are fast
      renewing and have a well-defined stem cell compartment that plays an essential
      role in homeostasis, and in treatment-induced acute injury that is dose limiting.
      Using recently defined intestinal stem cell markers and mouse models, a great
      deal of insight has been gained in the biology of intestinal stem cells (ISCs),
      which will undoubtedly help further mechanistic understanding of their injury.
      This review will cover historic discoveries and recent advances in the
      identification and characterization of intestinal stem cells, their responses to
      genotoxic stress, and a new crypt and intestinal stem cell culture system. The
      discussion will include key pathways regulating intestinal crypt and stem cell
      injury and regeneration caused by cancer treatments, and strategies for their
      protection. The focus will be on the acute phase of cell killing in mouse
      radiation models, where our understanding of the mechanisms in relation to
      intestinal stem cells is most advanced and interventions appear most effective.

PMID- 24683538
TI  - A Novel Method for Curvefitting the Stretched Exponential Function to
      Experimental Data.
AB  - The stretched exponential function has many applications in modeling numerous
      types of experimental relaxation data. However, problems arise when using
      standard algorithms to fit this function: we have observed that different
      initializations result in distinct fitted parameters. To avoid this problem, we
      developed a novel algorithm for fitting the stretched exponential model to
      relaxation data. This method is advantageous both because it requires only a
      single adjustable parameter and because it does not require initialization in the
      solution space. We tested this method on simulated data and experimental stress
      relaxation data from bone and cartilage and found favorable results compared to a
      commonly-used Quasi-Newton method. For the simulated data, strong correlations
      were found between the simulated and fitted parameters suggesting that this
      method can accurately determine stretched exponential parameters. When this
      method was tested on experimental data, high quality fits were observed for both
      bone and cartilage stress-relaxation data that were significantly better than
      those determined with the Quasi-Newton algorithm.

PMID- 24683539
TI  - Establishment and evaluation of stable cell lines inhibiting foot-and-mouth
      disease virus by RNA interference.
AB  - RNA interference (RNAi) has been proved to be a powerful tool for foot-and-mouth
      disease virus FMDV inhibition in vitro and in vivo. We established five stable
      baby hamster kidney 21 cell lines (BHK-21) containing five short hairpin RNAs
      (shRNAs) expression plasmids (p3D1shRNA, p3D2shRNA, p3D3shRNA, p3D4shRNA, and
      p3D5shRNA) targeting 3D gene of FMDV. Immunofluorescent assay, virus titration,
      and real-time quantitative reverse transcription polymerase chain reaction (Q-RT
      PCR) were conducted to detect the effect of shRNAs on FMDV replication. After
      challenged with FMDV of O/CHA/99, two cell lines (p3D1shRNA and p3D4shRNA) showed
      a significant reduction in the synthesis of viral protein and RNA, accompanied by
      a sharp decrease in viral yield, and the inhibition could last for at least
      thirty passages. We developed an efficient procedure for the establishment and
      evaluation of stable cell lines for anti-FMDV research based on RNAi technology,
      which can be a candidate method for anti-FMDV research. 

PMID- 24683540
TI  - In vivo analysis of trapeziometacarpal joint kinematics during pinch tasks.
AB  - This study investigated how the posture of the thumb while performing common
      pinch movements and the levels of pinch force applied by the thumb affect the
      arthrokinematics of the trapeziometacarpal joint in vivo. Fifteen subjects
      performed the pinch tasks at the distal phalange (DP), proximal interphalangeal
      (PIP) joint, and metacarpophalangeal (MP) joint of the index finger with 0%, 50%,
      and 80% of maximal pinch forces by a single-axis load cell. 3D images of the
      thumb were obtained using the computed tomography. The results show that the
      reference points moved from the central region to the dorsal-radial region when
      changing from pinching the DP to the MP joint without pinching force being
      applied. Pinching with 80% of the maximum pinching force resulted in reference
      points being the closest to the volar-ulnar direction. Significant differences
      were seen between 0% and 50% of maximum pinch force, as well as between 0% and
      80%, when pinching the MP joint in the distal-proximal direction. The effects of
      posture of the thumb and applied pinch force on the arthrokinematics of the joint
      were investigated with a 3D model of the trapeziometacarpal joint. Pinching with
      more than 50% of maximum pinch force might subject this joint to extreme
      displacement. 

PMID- 24683542
TI  - Transferrin-conjugated SNALPs encapsulating 2'-O-methylated miR-34a for the
      treatment of multiple myeloma.
AB  - Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat
      multiple myeloma (MM) were developed. Wild type or completely 2'-O-methylated
      (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with
      transferrin (Tf) in order to target MM cells overexpressing transferrin receptors
      (TfRs). The type of miR-34a chemical backbone did not significantly affect the
      characteristics of SNALPs in terms of mean size, polydispersity index, and zeta
      potential, while the encapsulation of an OMet miR-34a resulted in a significant
      increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical
      conjugation of SNALPs with Tf resulted in a significant decrease of the zeta
      potential, while size characteristics and miR-34a encapsulation into SNALPs were
      not significantly affected. In an experimental model of MM, all the animals
      treated with SNALPs encapsulating miR-34a showed a significant inhibition of the
      tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating
      OMet miR-34a resulted in the highest increase of mice survival. These results may
      represent the proof of concept for the use of SNALPs encapsulating miR-34a for
      the treatment of MM. 

PMID- 24683541
TI  - Antitumoral activity of snake venom proteins: new trends in cancer therapy.
AB  - For more than half a century, cytotoxic agents have been investigated as a
      possible treatment for cancer. Research on animal venoms has revealed their high
      toxicity on tissues and cell cultures, both normal and tumoral. Snake venoms show
      the highest cytotoxic potential, since ophidian accidents cause a large amount of
      tissue damage, suggesting a promising utilization of these venoms or their
      components as antitumoral agents. Over the last few years, we have studied the
      effects of snake venoms and their isolated enzymes on tumor cell cultures. Some
      in vivo assays showed antineoplastic activity against induced tumors in mice. In
      human beings, both the crude venom and isolated enzymes revealed antitumor
      activities in preliminary assays, with measurable clinical responses in the
      advanced treatment phase. These enzymes include metalloproteases (MP),
      disintegrins, L-amino acid oxidases (LAAOs), C-type lectins, and phospholipases
      A2 (PLA2s). Their mechanisms of action include direct toxic action (PLA2s), free
      radical generation (LAAOs), apoptosis induction (PLA2s, MP, and LAAOs), and
      antiangiogenesis (disintegrins and lectins). Higher cytotoxic and cytostatic
      activities upon tumor cells than normal cells suggest the possibility for
      clinical applications. Further studies should be conducted to ensure the efficacy
      and safety of different snake venom compounds for cancer drug development. 

PMID- 24683543
TI  - Systematic review on surgical and nonsurgical treatment of type II odontoid
      fractures in the elderly.
AB  - Odontoid fractures type II according to Anderson and d'Alonzo are not uncommon in
      the elderly patients. Still, due to the paucity of evidence the published
      treatment guidelines are far from equivocal. This systematic review focuses on
      the published results of type II odontoid fracture treatment in the elderly with
      regard to survival, nonunion, and complications. After a systematic literature
      research 38 publications were included. A cumulative analysis of 1284 published
      cases found greater survival if elderly patients with odontoid fractures type II
      received surgical treatment (RR = 0.64). With regard to nonunion in 669 published
      cases primary posterior fusion had the best fusion results. The systematic
      literature review came to the following conclusions. (1) Surgical stabilisation
      of odontoid fractures type II improves survival in patients between 65 and 85
      years of age compared to nonsurgical treatment. (2) Posterior atlantoaxial fusion
      for odontoid fractures type II in the elderly has the greatest bony union rate.
      (3) Odontoid nonunion is not associated with worse clinical or functional results
      in the elderly. (4) The complication rate of nonsurgical treatment is similar to
      the complication rate of surgical treatment of odontoid fractures type II in the
      elderly.

PMID- 24683544
TI  - Lipopolysaccharide stimulates p62-dependent autophagy-like aggregate clearance in
      hepatocytes.
AB  - Impairment of autophagy has been associated with liver injury. TLR4-stimulation
      by LPS upregulates autophagy in hepatocytes, although the signaling pathways
      involved remain elusive. The objective of this study was to determine the
      signaling pathway leading to LPS-stimulated autophagy in hepatocytes. Cell
      lysates from livers of wild type (WT; C57BL/6) mice given LPS (5 mg/kg-IP) and
      hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to
      24 h were collected. LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined
      by immunoblot, immunofluorescence, and qPCR. Autophagy-like activation was
      measured by GFP-LC3-puncta formation and LC3II-expression. Beclin1, Nrf2, p62,
      MyD88, and TIRAP were knocked-down using siRNA. LC3II-expression increased in
      both liver and hepatocytes after LPS and was dependent on TLR4. Beclin1
      expression did not increase after LPS in hepatocytes and beclin1-knockdown did
      not affect LC3II levels. In hepatocytes given LPS, expression of p62 increased
      and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPS
      induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of
      both Nrf2 and NF kappa B transcription factors to the nucleus to upregulate p62
      expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62
      mediated, not beclin1-mediated, autophagy-like clearance pathway that is
      hepatoprotective by clearing aggregate-prone or misfolded proteins from the
      cytosol and preserving energy homeostasis under stress.

PMID- 24683546
TI  - Rosiglitazone increases cerebral klotho expression to reverse baroreflex in type
      1-like diabetic rats.
AB  - Reduced baroreflex sensitivity (BRS) is widely observed in diabetic human and
      animals. Rosiglitazone is one of the clinically used thiazolidinediones (TZD)
      known as PPAR gamma agonist. Additionally, the klotho protein produced from
      choroid plexus in the central nervous system is regulated by PPAR gamma . In an
      attempt to develop the new therapeutic strategy, we treated streptozotocin
      induced diabetic rats (STZ) with rosiglitazone (STZ + TZD) orally at 10 mg/kg for
      7 days. Also, STZ rats were subjected to intracerebroventricular (ICV) infusion
      of recombinant klotho at a dose of 3 MU g/2.5 MU L via syringe pump (8 MU g/hr)
      daily for 7 days. The BRS and heart rate variability were then estimated under
      challenge with a depressor dose of sodium nitroprusside (50 MU g/kg) or a pressor
      dose of phenylephrine (8 MU g/kg) through an intravenous injection. Lower
      expression of klotho in medulla oblongata of diabetic rats was identified.
      Cerebral infusion of recombinant klotho or oral administration of rosiglitazone
      reversed BRS in diabetic rats. In conclusion, recovery of the decreased klotho in
      brain induced by rosiglitazone may restore the impaired BRS in diabetic rats.
      Thus, rosiglitazone is useful to reverse the reduced BRS through increasing
      cerebral klotho in diabetic disorders.

PMID- 24683545
TI  - Phytochemical prospection and modulation of antibiotic activity in vitro by
      Lippia origanoides H.B.K. in methicillin resistant Staphylococcus aureus.
AB  - The Lippia origanoides H.B.K. ethanol extract (LOEE) and hexane (LOHEX),
      dichloromethane (LODCM), and ethyl acetate (LOEA) fractions were tested for their
      antimicrobial activity alone or in combination with antibiotics against a
      methicillin resistant Staphylococcus aureus (MRSA) strain. The natural products
      did not show antimicrobial activity against multidrug resistant strain at the
      clinically significant concentrations tested. However, a modulatory effect in the
      antibacterial activity of the neomycin and amikacin was verified when LOEE, LOHEX
      and LODCM were added to the growth medium at subinhibitory concentrations. A
      similar modulation was found when the natural products were changed for
      chlorpromazine, an inhibitor of bacterial efflux pumps, suggesting the
      involvement of resistance mediated by efflux system in the MRSA tested. The
      fractions LOHEX and LODCM showed a modulatory activity bigger than their majority
      compounds (carvacrol, thymol, and naringenin), indicating that this activity is
      not due to their majority compounds only, but it is probably due to a synergism
      between their chemical components. These results indicate that L. origanoides
      H.B.K. can be a source of phytochemicals able to modify the phenotype of
      resistance to aminoglycosides in MRSA. 

PMID- 24683547
TI  - Association between postmenopausal osteoporosis and experimental periodontitis.
AB  - To investigate the correlation between postmenopausal osteoporosis (PMO) and the
      pathogenesis of periodontitis, ovariectomized rats were generated and the
      experimental periodontitis was induced using a silk ligature. The inflammatory
      factors and bone metabolic markers were measured in the serum and periodontal
      tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme
      linked immunosorbent assays, and immunohistochemistry. The bone mineral density
      of whole body, pelvis, and spine was analyzed using dual-energy X-ray
      absorptiometry and image analysis. All data were analyzed using SPSS 13.0
      statistical software. It was found that ovariectomy could upregulate the
      expression of interleukin- (IL-)6, the receptor activator of nuclear factor-
      kappaB ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10
      expression in periodontal tissues, which resulted in progressive alveolar bone
      loss in experimental periodontitis. This study indicates that changes of
      cytokines and bone turnover markers in the periodontal tissues of ovariectomized
      rats contribute to the damage of periodontal tissues.

PMID- 24683548
TI  - Identification of clinical phenotypes using cluster analyses in COPD patients
      with multiple comorbidities.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by persistent
      airflow limitation, the severity of which is assessed using forced expiratory
      volume in 1 sec (FEV1, % predicted). Cohort studies have confirmed that COPD
      patients with similar levels of airflow limitation showed marked heterogeneity in
      clinical manifestations and outcomes. Chronic coexisting diseases, also called
      comorbidities, are highly prevalent in COPD patients and likely contribute to
      this heterogeneity. In recent years, investigators have used innovative
      statistical methods (e.g., cluster analyses) to examine the hypothesis that
      subgroups of COPD patients sharing clinically relevant characteristics
      (phenotypes) can be identified. The objectives of the present paper are to review
      recent studies that have used cluster analyses for defining phenotypes in
      observational cohorts of COPD patients. Strengths and weaknesses of these
      statistical approaches are briefly described. Description of the phenotypes that
      were reasonably reproducible across studies and received prospective validation
      in at least one study is provided, with a special focus on differences in age and
      comorbidities (including cardiovascular diseases). Finally, gaps in current
      knowledge are described, leading to proposals for future studies.

PMID- 24683549
TI  - Alleviation of lead toxicity by 5-aminolevulinic acid is related to elevated
      growth, photosynthesis, and suppressed ultrastructural damages in oilseed rape.
AB  - Lead (Pb) is a widely spread pollutant and leads to diverse morphological and
      structural changes in the plants. In this study, alleviating role of 5
      aminolevulinic acid (ALA) in oilseed rape (Brassica napus L.) was investigated
      with or without foliar application of ALA (25 mg L(-1)) in hydroponic environment
      under different Pb levels (0, 100, and 400 uM). Outcomes stated that plant
      morphology and photosynthetic attributes were reduced under the application of Pb
      alone. However, ALA application significantly increased the plant growth and
      photosynthetic parameters under Pb toxicity. Moreover, ALA also lowered the Pb
      concentration in shoots and roots under Pb toxicity. The microscopic studies
      depicted that exogenously applied ALA ameliorated the Pb stress and significantly
      improved the cell ultrastructures. After application of ALA under Pb stress,
      mesophyll cell had well-developed nucleus and chloroplast having a number of
      starch granules. Moreover, micrographs illustrated that root tip cell contained
      well-developed nucleus, a number of mitochondria, and golgi bodies. These results
      proposed that under 15-day Pb-induced stress, ALA improved the plant growth,
      chlorophyll content, photosynthetic parameters, and ultrastructural modifications
      in leaf mesophyll and root tip cells of the B. napus plants.

PMID- 24683550
TI  - The c-MYC protooncogene expression in cholesteatoma.
AB  - Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle
      ear. The matrix of cholesteatoma is histologically similar to the matrix of the
      epidermoid cyst of the skin (atheroma); their epithelium is characterized by
      hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a
      transcription factor involved in the regulation of cell proliferation and
      differentiation. Previous studies have found aneuploidy of chromosome 8, copy
      number variation of c-MYC gene, and the presence of elevated level c-MYC protein
      in cholesteatoma. In this study we have compared the expression of c-MYC gene in
      samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11
      adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5
      normal skin samples (retroauricular region) using RT-qPCR, providing the first
      precise measurement of the expression of c-MYC gene in cholesteatoma. We have
      found significantly elevated c-MYC gene expression in cholesteatoma compared to
      atheroma and to normal skin samples. There was no significant difference,
      however, in c-MYC gene expression between cholesteatoma samples of children and
      adults. The significant difference in c-MYC gene expression level in
      cholesteatoma compared to that of atheroma implies a more prominent
      hyperproliferative phenotype which may explain the clinical behavior typical of
      cholesteatoma. 

PMID- 24683551
TI  - Does Interviewer Status Matter? An examination of Lay Interviewers and Medical
      Doctor Interviewers in an Epidemiological Study in Vietnam.
AB  - In 2006, typhoon Xangsane disrupted a large-scale multi-agency mental health
      study of 4,982 individuals in the DaNang province of Vietnam. Following this
      disaster, 795 of the original 4,982 participants were randomly assigned to be re
      interviewed by either a medical doctor or a lay interviewer using structured
      clinical interviews to determine prevalence of lifetime and post-typhoon post
      traumatic stress disorder (PTSD), major depressive disorder (MDD), panic disorder
      (PD), and generalized anxiety disorder (GAD) according to the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition (APA, 1994). The aim of
      the present study was to determine if prevalence of disorders differed by
      interviewer type. Bivariate analyses and multivariable analyses, as well as
      internal reliability estimates, all indicated no significant differences between
      the medical doctor interviewers versus the lay interviewers. This held for both
      lifetime prevalence as well as post-typhoon prevalence of disorders. This study
      has implications for epidemiologic studies, as it indicates that with adequate
      training, the use of lay interviewers may be a valid means of data collection.

PMID- 24683552
TI  - Weighting of Auditory Feedback Across the English Vowel Space.
AB  - Auditory feedback in the headphones of talkers was manipulated in the F1
      dimension using a real-time vowel formant filtering system. Minimum formant
      shifts required to elicit a response and the amount of compensation were measured
      for vowels across the English vowel space. The largest response in production of
      F1 was observed for the vowel /epsilon/ and smaller or non-significant changes
      were found for point vowels. In general, changes in production were of a
      compensatory nature that reduced the error in the auditory feedback.

PMID- 24683553
TI  - Interpretation of study design on marginal bone loss in implant dentistry:
      evidence-based science versus clinical-based experience.

PMID- 24683554
TI  - Correlation between interimplant distance and crestal bone loss in internal
      connection implants with platform switching.
AB  - PURPOSE: The aim of this study was to investigate the influence of interimplant
      distance of internal connection implants with platform switching on crestal bone
      loss using radiographic evaluation. MATERIALS AND METHODS: The present study
      included patients missing two consecutive teeth in the posterior quadrant and
      receiving internal connection implants. Digital periapical radiographs were taken
      at the time of superstructure connection and at the time of more than 1 year of
      loading. Bone level change was measured on the modified image using a digital
      subtraction program. The crestal bone loss between implants and the horizontal
      and vertical loss of peri-implant marginal bone were evaluated, and the influence
      of interimplant distance on crestal bone loss was analyzed at alpha = .05.
      RESULTS: A total of 10 pairs of implants having <= 3 mm of interimplant distance
      was included in this study (group 1). The other 15 pairs of implants having > 3
      mm of interimplant distance were selected as a control group (group 2). After the
      mean 19.3 months of observation, the mean crestal bone loss between implants was 
      0.26 +/- 0.14 mm in group 1 and -0.23 +/- 0.29 mm in group 2 (P > .05). There was
      no significant difference between the interimplant distance and the crestal bone
      loss according to the regression analysis (P = .765). The mean horizontal and
      vertical marginal bone loss was -0.18 +/- 0.25 mm and -0.15 +/- 0.18 mm,
      respectively, in group 1 and -0.17 +/- 0.31 mm and -0.11 +/- 0.33 mm,
      respectively, in group 2. There were no significant differences between outside
      and inside bone loss of implants in horizontal and vertical change (P > .05).
      CONCLUSIONS: Within the limitations of the short-term study, the interimplant
      distance did not affect the crestal bone loss with internal connection implants
      with platform switching. The horizontal and vertical marginal bone loss was found
      to be too small to result in overlapping loss of the interimplant crestal bone.

PMID- 24683555
TI  - Multifactorial evaluation of implant failure: a 19-year retrospective study.
AB  - PURPOSE: Dental implants generally provide good results as replacements for
      missing teeth, but a few patients experience implant failure. The aim of this
      retrospective study was to analyze the characteristics and causes of implant
      failures in hopes of reducing future failures. MATERIALS AND METHODS: Patients
      who received one or more implants at the Dental Hospital of Yonsei University
      College of Dentistry between February 1991 and May 2009 were included in this
      study. Data including age, sex, medical history, habits (eg, smoking and
      drinking), bone quality, primary stability, implant size, implant surface,
      additional surgical procedures, prosthetic type, clinical symptoms, implant
      failure date, and causes of implant failure were obtained through a chart review.
      Follow-up radiographs were compared to those obtained at baseline. The Pearson
      chi-square test and Fisher exact test were used to evaluate the correlations
      between risk factors and implant failure. RESULTS: In total, 879 patients
      received 2,796 implants; 150 implants in 91 patients had failed. Early and late
      implant failures occurred with 86 (57.3%) and 64 (42.7%) implants, respectively.
      The main causes of early and late implant failures were inflammation (47%) and
      overloading (53%), respectively. When the cause of early implant failure was
      inflammation, the failure rate was significantly higher for implants in the
      anterior maxilla; implants with poor primary stability, a machined surface, or a
      length exceeding 15 mm; and implants placed with a reconstructive procedure and
      two-stage surgery. When late implant failure was caused by overloading, the
      failure rate was significantly higher for implants with a machined surface,
      placed with a reconstructive procedure and/or two-stage surgery, and supporting
      telescopic dentures. CONCLUSION: Within the limitations of this study, the major
      causes of implant failure are inflammation and overloading, and they differ
      between early and late implant failures.

PMID- 24683556
TI  - Comparison of clinical performance of zirconia implants and titanium implants in
      animal models: a systematic review.
AB  - PURPOSE: This study aimed to compare the values of removal torque (RT) and bone
      implant contact (BIC) reported in different animal studies for zirconia and
      titanium implants. MATERIALS AND METHODS: A systematic review of the literature
      was performed to analyze BIC and RT of animal studies in which both zirconia and
      titanium dental implants were used. To identify the studies to include in this
      systematic review, an exhaustive search of PubMed was performed of animal studies
      published in English with reports on the quantification of the osseointegration
      of both titanium and zirconia implants by means of BIC and/or RT. The results
      were aggregated and analyzed within each of the animal models (pig, rabbit, rat,
      monkey, dog, and sheep). RESULTS: The selection process resulted in a final
      sample of 16 studies. In general, no significant differences were found between
      titanium and zirconia. The significant differences in terms of BIC and RT
      reported by the authors were attributable to the different surface treatments and
      microporosities of the implant surfaces studied, not to the materials themselves.
      Only two articles reported significantly lower BIC for modified zirconia implants
      as compared to modified titanium implants. Four authors described statistically
      significant differences in terms of RT between zirconia and titanium implants in
      the different animal models, regardless of the surface treatment received by the
      implants. CONCLUSIONS: Within the limitations of this study, the values for the
      BIC and RT of zirconia implants in most of the studies analyzed did not show
      statistical differences compared with titanium implants. Modified-surface
      zirconia may have potential as a candidate for a successful implant material,
      although further clinical studies are necessary.

PMID- 24683557
TI  - Histologic, histomorphometric, and radiographic monitoring of bone healing around
      in-office-sterilized orthodontic mini-implants with or without immediate load:
      study in rabbit tibiae.
AB  - PURPOSE: The objective of this study was to describe bone healing around self
      drilling orthodontic mini-implants (MIs), sterilized in an office with an
      autoclave, with or without immediate orthodontic loading. MATERIALS AND METHODS:
      One hundred forty-four self-drilling MIs (TOMAS, Dentaurum) were inserted into
      the tibiae of 18 white rabbits, with full-thickness flaps elevated under general
      anesthesia. An immediate load (50 cN) was applied to 50% of the MIs. Two rabbits
      were sacrificed soon after the surgery and served as a control group. Four
      rabbits each were sacrificed at 15, 21, 30, or 60 days after the surgeries.
      Digital radiographs were obtained to measure the cortical bone thickness (CBT)
      around and between the implants. Sections were obtained and stained for
      histologic and histomorphometric analysis. Bone quantity (BQ), bone-to-implant
      contact (BIC), and CBT were evaluated statistically. RESULTS: At day 0, fractures
      were visible in the cortical area around the MIs. At days 15 and 21, intense
      proliferation of woven bone followed by formation of lamellar bone was seen.
      After 30 days, primary bone was visible, with less proliferation activity. At day
      60, primary bone in the process of remodeling into secondary bone was apparent.
      BQ was better with loading after 15 days and increased throughout the healing
      period in the loaded and unloaded groups. Loading did not influence the BIC
      values, which increased with healing time for loaded and unloaded implants. CBT
      increased in all regions, and CBT was greater around the MIs than between them
      except for unloaded MIs in the 15-day group. CONCLUSION: An immediate, light
      orthodontic load did not affect the bone healing process around orthodontic MIs.
      Osseointegration and CBT increased and were time-related.

PMID- 24683558
TI  - Cleaning effectiveness of implant prophylaxis instruments.
AB  - PURPOSE: The aim of this study was to evaluate the cleaning effectiveness of
      implant prophylaxis instruments on polished and acid-etched implant surfaces.
      MATERIALS AND METHODS: Biofilm layers of Streptococcus mutans were grown on a
      total of 80 titanium disks; 40 disks were polished and 40 were acid-etched. Five
      disks of each surface were cleaned using each of seven implant prophylaxis
      instruments: (1) manual plastic curette, (2) manual carbon fiber-reinforced
      plastic (CFRP) curette, (3) sonic-driven prophylaxis brush, (4) rotating rubber
      cup with prophylaxis paste, (5) sonic-driven polyether ether ketone (PEEK)
      plastic tip, (6) ultrasonic-driven PEEK plastic tip, and (7) air polishing with
      amino acid (glycine) powder. Ten disks (five of each surface type) served as
      controls. After cleaning, the surfaces with remaining bacteria were assessed by
      light microscopy. Statistical analyses of the results were performed with one-way
      and two-way analyses of variance with Bonferroni-Dunn multiple comparisons post
      hoc analysis (alpha = .05). RESULTS: The cleaning effectiveness of the plastic
      curette was significantly lower than those of all machine-driven instruments on
      the polished surface. Significantly lower cleaning effectiveness occurred with
      the CFRP curette compared to the prophylaxis brush and to both oscillating PEEK
      plastic tips on the polished surface. The rubber cup provided less cleaning
      effectiveness compared to the ultrasonic PEEK plastic tip and air polishing on
      the acid-etched surface. Superior results, with less than 4% of the biofilm
      remaining, were obtained for both oscillating PEEK plastic tips and air polishing
      on both implant surfaces. The cleaning ability of the prophylaxis brush, rubber
      cup, and ultrasonic PEEK plastic tip differed significantly between both surface
      structures. CONCLUSIONS: Cleaning effectiveness, ie, less than 4% of the biofilm
      remaining, was not observed with all tested implant prophylaxis instruments. The
      cleaning ability of the devices depended on the implant surface structure.

PMID- 24683559
TI  - A pilot study of joint stability at the zirconium or titanium abutment/titanium
      implant interface.
AB  - PURPOSE: To compare the interfaces of loaded and unloaded zirconium and titanium
      abutments with titanium implants using scanning electron microscopy (SEM).
      MATERIALS AND METHODS: Zirconium and titanium abutments (n = 5 per group; four
      test and one control) were torque-tightened into titanium implants secured into
      metal blocks, and computer-aided design/computer-assisted manufacture-based
      zirconium oxide copings were fabricated and cemented to the abutments with
      temporary resin-based cement. Specimens of each restoration were subjected to
      cyclic axial and lateral loading of 30 N at 2 Hz for 500,000 cycles using a
      servohydraulic test system; control specimens were left unloaded. Then, the
      abutment/implant assemblies were embedded in acrylic resin, sectioned
      longitudinally along the midline, and inspected under SEM with x-ray
      microanalysis. RESULTS: Loosening or fracture of the copings and implant
      components was not observed after dynamic loading in both groups. SEM and x-ray
      microanalysis revealed unexpected microleakage of acrylic resin at the interface.
      Acrylic resin in the implants tightened to the titanium abutments was limited to
      the cervical part, and the components displayed scratched and smashed regions,
      suggesting slight deformation of the implant neck. Microleakage and pooling of
      acrylic resin were observed approaching the screw joint in loaded implants
      tightened to zirconia abutments, and the amount of microleakage was greater than
      in the unloaded control specimens, which had a larger microgap than the titanium
      abutment/titanium implant interface. Loaded zirconia abutments were associated
      with wear, scratches, and, in one sample, chipping. CONCLUSIONS: Zirconium
      abutment/titanium implant interface may be susceptible to wear of the abutment
      coupled with deformation of the implant neck greater than that associated with
      the conventional titanium abutment/titanium implant interface under dynamic
      loading.

PMID- 24683560
TI  - Comparison of implant success rates with different loading protocols: a meta
      analysis.
AB  - PURPOSE: To systematically evaluate implant success rates with different loading
      protocols. MATERIALS AND METHODS: A search was conducted of electronic databases,
      including The Cochrane Oral Health Group's Trials Register, PubMed, SciSearch,
      Medline, and EMBASE, for all randomized controlled trials published between 1997
      and 2011 to compare implant success rates among different loading methods. The
      quality of randomized controlled trials was critically appraised, and the data
      were extracted by two independent reviewers. Meta-analyses were conducted of the
      eligible randomized controlled trials. RESULTS: A total of 26 randomized
      controlled trials met the criteria for meta-analysis. The quality of these
      articles was moderate. Eight trials compared immediate and early loading
      (relative risk [RR] = 0.90, 95% confidence interval [CI] 0.42-1.93, P = .79), 7
      compared early with delayed loading (RR = 1.19, 95% CI 0.52-2.72, P = .69), and
      11 compared immediate and delayed loading (RR = 1.19, 95% CI 0.52-2.72, P = .69).
      CONCLUSIONS: The limited evidence shows that there is no significant difference
      in implant success rates with different loading protocols.

PMID- 24683561
TI  - The impact of a laser-microtextured collar on crestal bone level and clinical
      parameters under various placement and loading protocols.
AB  - PURPOSE: Physical attachment of connective tissue fibers to a laser-microtextured
      (8- and 12-MUm grooves) surface on the collar of an implant has been demonstrated
      using human histology. Related clinical research has suggested that this
      microtextured surface may help to decrease initial bone loss after implant
      placement. The aim of this retrospective study was to compare crestal bone
      heights and clinical parameters between implants with laser-microtextured and
      machined collars placed and loaded with different protocols. MATERIALS AND
      METHODS: This study evaluated 300 single implants in 300 patients (155 men, 145
      women; mean age: 49.3 years; range: 45 to 75 years). One hundred sixty implants
      with laser-microtextured collars (L) and 140 with machined collars (M) were used.
      Implants were grouped into the treatment categories of immediate placement,
      delayed placement, immediate nonocclusal loading, and delayed loading. For all
      groups, crestal bone level, attachment level (CAL), Plaque Index, and bleeding on
      probing were recorded at baseline and 6, 12, and 24 months after loading with the
      definitive restoration. RESULTS: Nine implants were lost (four L and five M). The
      type of implant and timing of placement and loading showed no significant
      influence on survival rates. A mean CAL loss of 1.12 mm was observed during the
      first 2 years in the M group, while the mean CAL loss observed in the L group was
      0.55 mm. Radiographically, L group implants showed a mean crestal bone loss of
      0.58 mm, compared to 1.09 mm for the M group. CONCLUSION: A laser-microtextured
      surface on the implant collar may mitigate the negative sequelae associated with
      peri-implant bone loss, regardless of the placement and loading protocols used.

PMID- 24683562
TI  - Fatigue resistance and failure mode of adhesively restored custom metal-composite
      resin premolar implant abutments.
AB  - PURPOSE: To evaluate the fatigue resistance and failure mode of composite resin
      and porcelain onlays and crowns bonded to premolar custom metal-composite resin
      premolar implant abutments. MATERIALS AND METHODS: Sixty composite resin
      mesostructures were fabricated with computer assistance with two preparation
      designs (crown vs onlay) and bonded to a metal implant abutment. Following
      insertion into an implant with a tapered abutment interface (Titamax CM), each
      metal-composite resin abutment was restored with either composite resin (Paradigm
      MZ100) or ceramic (Paradigm C) (n = 15) and attached with adhesive resin
      (Optibond FL) and a preheated light-curing composite resin (Filtek Z100). Cyclic
      isometric chewing (5 Hz) was then simulated, starting with 5,000 cycles at a load
      of 50 N, followed by stages of 200, 400, 600, 800, 1,000, 1,200, and 1,400 N
      (25,000 cycles each). Samples were loaded until fracture or to a maximum of
      180,000 cycles. The four groups were compared using life table survival analysis
      (log-rank test). Previously published data using zirconia abutments of the same
      design were included for comparison. RESULTS: Paradigm C and MZ100 specimens
      fractured at average loads of 1,133 N and 1,266 N, respectively. Survival rates
      ranged from 20% to 33.3% (ceramic crowns and onlays) to 60% (composite resin
      crowns and onlays) and were significantly different (pooled data for restorative
      material). There were no restoration failures, but there were adhesive failures
      at the connection between the abutment and the mesostructure. The survival of the
      metal-composite resin premolar abutments was inferior to that of identical
      zirconia abutments from a previous study (pooled data for abutment material).
      CONCLUSIONS: Composite resin onlays/crowns bonded to metal-composite resin
      premolar implant abutments presented higher survival rates than comparable
      ceramic onlays/crowns. Zirconia abutments outperformed the metal-composite resin
      premolar abutments.

PMID- 24683563
TI  - Comparison of five-axis milling and rapid prototyping for implant surgical
      templates.
AB  - PURPOSE: This study aims to compare and evaluate the accuracy of surgical
      templates fabricated using coordinate synchronization processing with five-axis
      milling and design-related processing with rapid prototyping (RP). MATERIALS AND
      METHODS: Master phantoms with 10 embedded gutta-percha cylinders hidden under
      artificial gingiva were fabricated and imaged using cone beam computed
      tomography. Vectors of the hidden cylinders were extracted and transferred to
      those of the planned implants through reverse engineering using virtual planning
      software. An RP-produced template was fabricated by stereolithography in
      photopolymer at the RP center according to planned data. Metal sleeves were
      bonded after holes were bored (group RP). For the milled template, milling
      coordinates were synchronized using the conversion process for the coordinate
      synchronization platform located on the model's bottom. Metal bushings were set
      on holes milled on the five-axis milling machine, on which the model was fixed
      through the coordinate synchronization plate, and the framework was constructed
      on the model using orthodontic resin (group CS). A computed tomography image was
      taken with templates firmly fixed on models using anchor pins (RP) or anchor
      screws (CS). The accuracy was analyzed via reverse engineering. Differences
      between the two groups were compared by repeated measures two-factor analysis.
      RESULTS: From the reverse-engineered image of the template on the experimental
      model, RP-produced templates showed significantly larger deviations than did
      milled surgical guides. Maximum deviations of the group RP were 1.58 mm
      (horizontal), 1.68 mm (vertical), and 8.51 degrees (angular); those of the group
      CS were 0.68 mm (horizontal), 0.41 mm (vertical), and 3.23 degrees (angular).
      CONCLUSIONS: A comparison of milling and RP template production methods showed
      that a vector-milled surgical guide had significantly smaller deviations than did
      an RP-produced template. The accuracy of computer-guided milled surgical
      templates was within the safety margin of previous studies.

PMID- 24683564
TI  - Dental implants in cleft lip, alveolus, and palate patients: a systematic review.
AB  - PURPOSE: Missing teeth are a major problem in cleft patients, who require
      specialized prosthetic management, including dental implants. The aim of this
      review was to investigate the optimal date for implant insertion in patients born
      with cleft lip and palate after bone grafting and to assess the long-term
      prognosis of the inserted dental implants. MATERIALS AND METHODS: A systematic
      review of the current literature electronically in several databases and
      additional hand searching were performed. Relevant publications were assessed
      with regard to their evidence according to the guidelines of the Oxford Centre
      for Evidence-Based Medicine. RESULTS: Forty-nine publications (prospective and
      retrospective clinical studies, case series, and case reports) were included for
      analysis, but only 18 clinical papers reported survival rates for dental implants
      (in all, 670 implants in 460 cleft patients). Most studies were evidence level 3b
      (case-control studies) or 4 (case series, case reports). Reported 5-year survival
      rates for dental implants in cleft patients ranged from 80% to 96% (mean, 88.6%).
      Implant placement is favored after growth is complete and is generally
      recommended within 4 to 6 months after bone grafting. CONCLUSIONS: Dental
      implants in patients with cleft lip and palate show high success rates and allow
      for sufficient oral rehabilitation. However, because of a lack of sufficient
      prospective clinical studies on dental implants in cleft patients, the available
      evidence is poor and insufficient.

PMID- 24683565
TI  - Changes in general and oral health-related quality of life in immediate or
      conventionally loaded dental implants: a nonrandomized clinical trial.
AB  - PURPOSE: To evaluate changes in the general and oral health-related quality of
      life (using the European Quality of Life indicator and the Oral Health Impact
      Profile-49 [OHIP-49], respectively) of patients treated with conventionally or
      immediately loaded implants. MATERIALS AND METHODS: This clinical trial consisted
      of a clinical oral examination and a questionnaire-based interview carried out
      before and after both surgery and definitive prosthetic rehabilitation in a
      consecutive sample of patients requiring dental implants. According to the
      clinical diagnosis and patient preference, patients were assigned to the
      immediate loading group (IL group; n = 29) or the conventional loading group (CL
      group; n = 75). The change summary scores and effect sizes were calculated in the
      intermediate stage and at the final follow-up, taking baseline scores as
      reference. RESULTS: The oral health-related quality of life and oral satisfaction
      after implant therapy were significantly better than at baseline, with an even
      greater benefit when the implants were loaded immediately than when prosthetic
      rehabilitation was delayed. However, there were no significant differences in
      between-group comparisons in the ratings of general health status. The effect
      size for the OHIP-49 exceeded the threshold value of 0.8 for the domains
      functional limitation, pain/discomfort, and psychological discomfort in both
      groups and also for physical disability and psychological disability in the IL
      group. CONCLUSIONS: A gradual improvement in oral well-being scores, but not in
      those of general well-being, were observed for both groups from the intermediate
      stage to the final evaluation. This benefit was markedly greater for the IL
      group.

PMID- 24683566
TI  - The effect of graft bone particle size on bone augmentation in a rabbit cranial
      vertical augmentation model: a microcomputed tomography study.
AB  - PURPOSE: The purpose of this study was to investigate the impact of graft bone
      particle size on autogenous bone graft augmentation in a vertical augmentation
      chamber model. MATERIALS AND METHODS: A total of 12 rabbits were used in this
      study. The donor bone particles were of different sizes: small (150 to 400 MUm),
      large (1.0 to 2.0 mm), and a mixture comprising equal weights of both large and
      small bone particles. One type of bone graft material was placed into each of two
      polytetrafluoroethylene chambers that were implanted in the parietal bone of each
      rabbit's cranium. Animals were sacrificed 4 or 8 weeks after the grafting
      procedure. The recovered samples were analyzed by microcomputed tomography (micro
      CT) for quantitative analysis. Total bone volume, bone height, and the
      distribution of bone structure were calculated by micro-CT. RESULTS: Micro-CT
      evaluations revealed that the bone grafts performed with large bone particles
      provided, statistically, the best outcome. Total bone volume and bone height
      decreased in a time-dependent manner, and there was a statistically significant
      reduction in total bone volume between 4 and 8 weeks in the group with the mixed
      bone particle sizes. CONCLUSION: Within the limitations of the present study,
      large bone graft particles provided the best preservation of total bone volume
      and bone height up to 8 weeks after grafting in an animal vertical augmentation
      model.

PMID- 24683567
TI  - Maxillary sinus floor elevation using the osteotome technique in the presence of
      antral pseudocysts: a retrospective study with an average follow-up of 27 months.
AB  - PURPOSE: This retrospective study investigated the predictability of the
      osteotome technique for sinus floor elevation in the presence of antral
      pseudocysts. MATERIALS AND METHODS: A retrospective study was carried out in
      patients treated with the osteotome technique for sinus floor elevation in the
      presence of antral pseudocysts and simultaneous implant placement between 2005
      and 2009. Pseudocyst cases were collected from the patient population during that
      period based on faint dome-shaped radiographic findings in the elevated sinus
      floor. Data were recorded and evaluated in terms of bone gain and alterations in
      the sinus floor and peri-implant parameters. RESULTS: Twenty-one patients were
      diagnosed with antral pseudocysts in the sinus floor, with 21 implants placed
      underneath. All implants osseointegrated uneventfully, and all but one implant
      radiographically appeared to gain bone around the apex. Mean residual bone height
      was 6.85 +/- 1.22 mm and the mean length of implants protruding into the sinus
      was 2.96 +/- 1.16 mm. The mean endosinus bone gain after the healing period was
      3.40 +/- 1.78 mm, with an average crestal bone loss of 0.85 +/- 0.42 mm. Thirteen
      implants showed healed bone graft extending all around the apices, three implants
      had major bony coverage (50% to 100%) of the apically protruding portion, and
      four implants showed less coverage (< 50%). The survival rate of implants was
      100% (mean follow-up, 27.26 +/- 15.22 months), and at that time, mean crestal
      bone loss was 0.50 +/- 0.33 mm, modified Plaque Index was 1.30 +/- 0.67, modified
      Bleeding Index was 0.60 +/- 0.70, and mean probing depth was 3.35 +/- 0.74 mm.
      CONCLUSION: Based upon a retrospective study of 21 implants placed beneath
      pseudocysts for a mean time of 27 months, it appears that implants that extend
      into the maxillary sinus can remain functionally stable after osteotome sinus
      elevation in the presence of antral pseudocysts.

PMID- 24683568
TI  - Antral balloon sinus elevation and grafting prior to dental implant placement:
      review of 34 cases.
AB  - PURPOSE: The objective of this study was to assess the antral balloon technique
      for sinus elevation followed by bone graft and implant placement. MATERIALS AND
      METHODS: A total of 34 patients with atrophic edentulous posterior maxillary
      ridges underwent antral balloon sinus elevation followed by bone grafting
      (autogenous bone retrieved from the chin mixed with platelet-rich plasma) and
      implant placement. RESULTS: The population consisted of 26 male and 8 female
      patients with a mean age of 42 years (range, 33 to 56 years). Successful sinus
      membrane balloon elevation was performed in all 34 patients, and 62 implants were
      placed. A membrane tear in one patient was managed intraoperatively by placement
      of a collagen membrane. Two implants failed within 6 months, and the survival
      rate of the other 60 implants was 100% after 3 years of follow-up. The mean
      inflated balloon volume was 1.96 mL and the mean elevated sinus height by balloon
      was 11.6 mm. An average bone gain of 7.5 mm (range, 5.2 to 10.5 mm) was observed.
      CONCLUSIONS: This case series demonstrates the feasibility of antral balloon
      sinus membrane elevation followed by bone augmentation and implant placement.
      This technique offers optimal assurance for membrane safety, and it is less
      invasive than the routine lateral window technique, safe, and associated with
      less postoperative bleeding and discomfort. This method is predictable, easy to
      learn, and associated with low complication rates. However, large comparative
      studies with other techniques are required.

PMID- 24683569
TI  - Long-term prospective study of an orthodontic bone anchor.
AB  - PURPOSE: (1) To determine whether immediate loading of orthodontic bone anchors
      (OBAs) generates more failures than delayed loading and (2) to evaluate the
      impact of different variables on the success rate of the use of OBAs as temporary
      anchorage devices in orthodontic treatment. MATERIALS AND METHODS: In a
      prospective registry, consecutive patients were treated with OBAs by one
      experienced maxillofacial surgeon. An independent evaluator compared and analyzed
      different prospectively determined parameters: gender, age (young [< 16 years]
      versus mature [>= 16 years]), time of loading (delayed versus immediate), jaw,
      location, fixation screw length, complications, and orthodontic indications.
      Success with the OBA was defined as the capacity to maintain anchorage throughout
      treatment. Premature removal of an OBA because of infection, serious mobility, or
      persistent pain was considered a failure. Fisher exact tests for analysis of
      associations between the categorical variables, with the patient as independent
      variable, were performed. Success and complications were evaluated using
      multivariate logistic regression. RESULTS: Sixty-one patients (37 male, 24
      female) were treated with 106 OBAs over a 5-year period (2001 to 2006). The
      reported success rate in this study was 88.3%. In seven patients (11.7%) an OBA
      was removed prematurely. Age, gender, time of loading, jaw, and location did not
      influence the failure rate. In 25% of patients, at least one screw failure was
      noted. A statistically higher screw failure rate was noted in female patients,
      and the younger group presented more complications than the mature group.
      CONCLUSION: According to the results of this study, OBAs are a reliable means to
      obtain absolute orthodontic anchorage. Immediate loading of an OBA did not
      generate more failures than delayed loading. Age, jaw, and position did not seem
      to play important roles in success. Age and gender were important parameters in
      fixation screw failure rate.

PMID- 24683570
TI  - Distal cantilever in full-arch prostheses and immediate loading: a retrospective
      clinical study.
AB  - PURPOSE: The purpose of this study was to analyze and evaluate the clinical
      success of distal cantilevers of fixed full-arch prostheses for the
      rehabilitation of edentulous arches in conjunction with immediate loading.
      MATERIALS AND METHODS: Twenty-seven patients (15 men and 12 women) with a mean
      age of 59 years received 203 implants (Ankylos, Dentsply), either in edentulous
      jaws or after extraction and immediate implant placement. All implants were
      splinted together with provisional restorations and loaded immediately after
      surgery. After an average of 60 days, the definitive prostheses were fabricated
      and cemented provisionally. Thirty-one prostheses were delivered. A total of 92
      units on distal cantilevers were incorporated into the prostheses. Implant
      stability was recorded (via percussion testing) after prostheses were removed and
      crestal bone levels were measured with radiographs. RESULTS: Average crestal bone
      loss was 0.33 mm. After a follow-up of 5 years, only one prosthesis broke (at the
      connection between the main part of the denture and the distal extension). A
      total of five implants were lost because of overloading or peri-implantitis
      (during early healing). The success rate of implants was 94.5%, the survival rate
      was 97.5%, and the survival rate of the prostheses was 96.7% after a loading
      period of 79.30 +/- 35.31 months. CONCLUSIONS: Based on the long-term clinical
      data, distal cantilevers on a full-arch prosthesis can be a successful treatment
      modality and can be employed in patient treatment planning when posterior support
      is indicated.

PMID- 24683571
TI  - Effects of connective tissue grafting on the facial gingival level following
      single immediate implant placement and provisionalization in the esthetic zone: a
      1-year randomized controlled prospective study.
AB  - PURPOSE: This 1-year randomized controlled prospective study evaluated the
      implant success rate and peri-implant tissue response following single immediate
      implant placement and provisionalization (IIPP) with and without subepithelial
      connective tissue graft (SCTG) in the esthetic zone. MATERIALS AND METHODS:
      Implants were placed either IIPP with SCTG (test group) or IIPP without SCTG
      (control group). The implants were evaluated both clinically and radiographically
      before surgery, immediately after implant placement, and 3, 6, and 12 months
      after implant placement. Data were analyzed using Friedman, Wilcoxon signed-rank,
      and Mann-Whitney U tests at the significance level of alpha = .05. RESULTS:
      Twenty implants (10 test, 10 control) were placed in 20 patients (7 men, 13
      women) between the ages of 27 and 87 (mean age, 52.6 years). At 1 year, all
      implants remained osseointegrated, with overall mean marginal bone changes of 
      0.01 mm and -0.14 mm for the test and control groups, respectively. Mean facial
      gingival level change was significantly more pronounced in the control group (
      0.70 mm) than in the test group (-0.25 mm). The modified Plaque Index scores
      showed that patients were able to maintain a good level of hygiene throughout the
      study. At 1 year, the Papilla Index indicated that more than 50% papilla fill was
      observed in 75% of the test sites and 80% of the control sites. CONCLUSIONS:
      Within the limitations of this study, SCTG was shown to be beneficial in
      maintaining facial gingival level when performed in conjunction with IIPP
      procedures.

PMID- 24683572
TI  - Radiographic evaluation of crestal bone levels of delayed implants at medium-term
      follow-up.
AB  - PURPOSE: The aim of this study was to evaluate the radiographic bone level
      changes after delayed implant placement at medium-term follow-up, with three
      elements kept constant: keratinized gingiva thickness, implant axes perpendicular
      to the opposing occlusal surface, and implants with a collar of 2 mm. MATERIALS
      AND METHODS: Patients treated in a private practice setting were retrospectively
      enrolled in the study. They underwent delayed placement (4 to 8 weeks after
      extraction) of dental implants in edentulous premolar or molar regions. Implants
      followed a delayed loading protocol. Crestal bone levels were measured at
      baseline; at provisional prosthesis placement; at 1, 3, and 5 years; and at
      medium-term follow-up of healing from implant placement. RESULTS: One hundred
      twenty patients received 135 implants (one or two implants per patient); 3
      implants were lost. After a mean follow-up period of 9.71 +/- 4.88 years, a
      survival rate of 97.76% was reported. At 1 year after implant placement, mean
      bone loss of -1.5 +/- 0.62 mm was found. At almost 3 years post-implant
      placement, a mean bone gain of +1.20 +/- 0.49 mm was seen, which was
      statistically significantly different compared with 1 year. After this point, the
      bone levels remained stable; similar values were reported over time, with no
      significant differences. CONCLUSIONS: The mean vertical bone gain of +1.20 +/-
      0.49 mm seen at almost 3 years after implant placement in this study may be
      supported by both clinical parameters as presence of sufficiently thick
      keratinized gingiva (3 mm), implants with a 2-mm collar, and the axis of implant
      insertion perpendicular to the opposing occlusal surface.

PMID- 24683573
TI  - Clinical outcome of narrow-diameter (3.3-mm) locking-taper implants: a
      prospective study with 1 to 10 years of follow-up.
AB  - PURPOSE: To evaluate the outcome of narrow-diameter (3.3-mm) locking-taper
      implants used in the rehabilitation of partially and fully edentulous patients
      over a 10-year period. MATERIALS AND METHODS: Between January 2002 and December
      2011, all patients referred to a private dental clinic for treatment with narrow
      diameter implants were enrolled in this study. At each annual follow-up session,
      clinical and radiographic parameters were assessed; the outcome measurements were
      implant failure, peri-implant marginal bone loss (distance between the implant
      shoulder and the first visible bone-to-implant contact [DIB]), and biologic and
      technical complications. The cumulative survival rate (CSR) was assessed using
      the Kaplan-Meier survival estimator; Tarone-Ware and chi-square analyses were
      used to evaluate correlations between the study variables. The statistical
      analysis was performed at the patient- and implant-level. RESULTS: A total of 324
      narrow-diameter implants were placed in 279 patients (159 men, 120 women; age: 25
      to 73 years). Four implants failed, for an overall CSR of 98.5% (patient-based)
      and 98.7% (implant-based) at the 10-year follow-up. The survival rate did not
      differ significantly with respect to patients' sex, age, smoking or
      parafunctional habits, bone type, prosthetic restoration, or implant location,
      position, or length. Among the surviving implants, a mean DIB of 0.31 +/- 0.23
      mm, 0.45 +/- 0.27 mm, and 0.69 +/- 0.28 mm was observed at the 1-, 5-, and 10
      year follow-up examinations, respectively. A few biologic (1.2%) and technical
      complications (7.5%) were reported. CONCLUSIONS: Within the limitations of this
      study, it can be concluded that narrow-diameter locking-taper implants represent
      a good treatment option for the prosthetic rehabilitation of partially and
      totally edentulous patients.

PMID- 24683574
TI  - Sensitivity of resonance frequency analysis for detecting early implant failure:
      a case-control study.
AB  - PURPOSE: The aim of this study was to test the sensitivity of the resonance
      frequency analysis for detecting early implant failure. MATERIALS AND METHODS: In
      all, 3,786 implants placed from June 2007 to January 2013 were retrospectively
      evaluated. A total of 20 implants (in 20 patients) placed in pristine bone were
      found to have failed before loading. The implant stability quotient (ISQ) values
      were extracted from these 20 implants at baseline (immediate) and 4 months after
      placement (delayed). Simple linear regression, logistic regression, and two-way
      contingency tables were used to test for the relationships between ISQ values and
      early implant failure. RESULTS: Immediate ISQ values were significantly related
      to failure (odds ratio [OR] = 4.27). Furthermore, the results of the second
      regression showed a significant relationship between ISQ at delayed measurement
      and implant failure (OR = 9.20). For immediate ISQ, it seems that the 73.7%
      correct classifications were obtained at the cost of an incorrect classification
      of 55% of the implant failures. However, for the delayed ISQ, 86.2% correct
      classifications were obtained at the cost of assuming that all implants will
      survive. CONCLUSION: The present study showed that ISQ values are not reliable in
      predicting early implant failure. In addition, the real cutoff ISQ value to
      differentiate between success and early implant failure remains to be determined.

PMID- 24683575
TI  - The influence of cortical perforation on guided bone regeneration using synthetic
      bone substitutes: a study of rabbit cranial defects.
AB  - PURPOSE: The purpose of this study was to investigate the influence of cortical
      perforation on angiogenesis and osteogenesis following guided bone regeneration
      using synthetic bone substitutes in rabbit cranial defects. MATERIALS AND
      METHODS: The right and left sides of the calvaria were exposed in 11 rabbits. In
      each rabbit, two custom-made titanium domes were placed on either side of the
      midline. In experimental sites, the cortical surface inside the boundary of one
      of the two circular slits was then mechanically perforated five times with a
      round bur; in control sites, this was left intact. All sites received beta
      tricalcium phosphate. The animals were sacrificed at 2, 4, and 8 weeks. Biopsy
      samples were examined histomorphometrically by light microscopy, and the
      expression of vascular endothelial growth factor (VEGF) and osteocalcin (OC) was
      determined immunohistochemically. RESULTS: The percent area of newly formed bone
      was significantly higher in the experimental group than in the control group 2
      weeks after surgery. Marrow cells reached the normal rabbit calvarial bone more
      rapidly in experimental sites than in control sites. Immunostaining intensity and
      the percentage of positively stained cells for VEGF were greater in the
      experimental group than in the control group at 2 weeks after surgery. At 4
      weeks, immunostaining intensity and the percentage of positively stained cells
      for OC were greater in the experimental group than in the control group. However,
      there were no significant differences between the experimental and control groups
      in immunohistochemical findings for VEGF and OC. CONCLUSIONS: The results of this
      study suggest that cortical perforation of the receptor bone may improve
      angiogenesis in bone grafts and increase the amount of newly formed bone in
      grafted areas, especially in the early bony healing phase. Further studies in
      larger samples are needed to confirm these results.

PMID- 24683576
TI  - Influence of titanium ions on cytokine levels of murine splenocytes stimulated
      with periodontopathic bacterial lipopolysaccharide.
AB  - PURPOSE: Titanium (Ti) is frequently used in dental implants because of its
      excellent corrosion resistance, mechanical properties, and biocompatibility.
      However, Ti ions may be slowly released as a result of corrosion, contributing to
      peri-implantitis, a major cause of dental implant failure. This study examined
      the influence of Ti ions on cytokine levels in murine splenocytes, an
      immunocompetent cell type, stimulated with Aggregatibacter actinomycetemcomitans
      lipopolysaccharide (LPS) and the influence of Ti ions on splenocyte viability.
      MATERIALS AND METHODS: Splenocytes were prepared from 5- to 10-week-old male
      C57BL/6 mice and BALB/c mice. Cytokine levels in culture supernatants from murine
      splenocytes stimulated with A actinomycetemcomitans LPS were determined with
      enzyme-linked immunosorbent assay. A tetrazolium salt assay was carried out to
      evaluate the cytotoxicity of Ti ions against murine splenocytes. RESULTS: The
      present study demonstrated that Ti ions influence cytokine levels in LPS
      stimulated splenocytes. Significantly higher values (P < .05) were observed for
      interleukins 1beta, 6, and 10; interferon-gamma; tumor necrosis factor alpha; and
      granulocyte macrophage colony-stimulating factor in the culture supernatants of
      LPS-stimulated splenocytes of both mouse strains in the presence of Ti ions, as
      compared to the absence of Ti ions. Tetrazolium salt assay confirmed that the Ti
      ions used in this study did not affect the viability of murine splenocytes.
      CONCLUSION: This study suggests that Ti ions enhanced cytokine production induced
      by periodontopathic bacterial LPS.

PMID- 24683577
TI  - Bone formation on biomimetic calcium phosphate-coated and zoledronate-immobilized
      titanium implants in osteoporotic rat tibiae.
AB  - PURPOSE: Coating prostheses with calcium phosphate (CaP) can boost ossification
      and provide an appropriate vehicle for drug delivery. In this study, CaP coating
      was performed using a biomimetic method, and zoledronate (ZOL) was incorporated
      to promote peri-implant bone formation in an osteoporotic environment. MATERIALS
      AND METHODS: Twenty female 8-week-old rats were ovariectomized to induce
      osteoporosis. Twelve weeks later, the animals were randomly separated into four
      groups representing different ZOL concentrations in the immersion solution: 0
      (control), 8, 80, and 800 MUg/mL. Surface-treated implants were inserted in both
      tibiae, and the rats were sacrificed 8 weeks after implantation. Specimens were
      retrieved for histomorphometric and microcomputed tomographic analyses. RESULTS:
      A thin CaP coating was formed on the surface of the titanium implants, and ZOL
      was successfully incorporated into the structure of the biomimetic CaP coating.
      There were significant differences between the groups with regard to bone volume,
      whereas bone-implant contact comparisons did not yield any significant
      differences. The microstructural results clearly illustrated the positive effect
      of ZOL loading on the implants, as compared to the controls. CONCLUSIONS: The
      data suggest that biomimetic CaP coating followed by bisphosphonate
      immobilization is effective in improving bone quality and preserving bone volume
      around dental implants; therefore, this technique may be beneficial for
      osteoporosis patients.

PMID- 24683578
TI  - Using growth factors in human extraction sockets: a histologic and
      histomorphometric evaluation of short-term healing.
AB  - PURPOSE: Ridge preservation protocols reduce crestal remodeling after tooth
      extraction. There is insufficient evidence on bone grafting in combination with
      platelet-rich plasma (PRP) or recombinant human platelet-derived growth factor
      (rhPDGF-BB). The aim of this study is to evaluate healing of grafted and
      nongrafted sockets and the effect of PRP and rhPDGF-BB on early remodeling.
      MATERIALS AND METHODS: Forty-one patients whose treatment plan included
      extraction of anterior or premolar teeth were randomized into four groups. Group
      1: collagen plug (control). Group 2: mineralized freeze-dried bone allograft
      (FDBA)/beta-tricalcium phosphate (beta-TCP)/collagen plug. Group 3: FDBA/beta
      TCP/PRP/collagen plug. Group 4: FDBA/beta-TCP/rhPDGF-BB/collagen plug. At 8
      weeks, a core was harvested from the center of 41 sockets. Histomorphometric
      analysis took place. Differences were analyzed using one-way analysis of variance
      (ANOVA) or chi-square tests for continuous and categorical data. Pairwise
      comparisons were tested using least squares means. Spearman correlation
      coefficients were used to evaluate the relationship of bone growth with potential
      confounders. A P value < .05 was considered statistically significant. RESULTS:
      ANOVA did not indicate statistical significance in age, gender, smoking,
      ethnicity, or race distribution. Significant differences in tissue distribution
      were identified between groups and between different thirds of harvested core.
      More new bone and amorphous organic matrix was noted in the control group. In
      sites where bone graft was combined with growth factors, the amount of residual
      particles was less than in sites where bone graft was used alone. CONCLUSIONS:
      Inclusion of bone replacement graft suppressed new bone formation during early
      healing. Inclusion of PRP and rhPDGF-BB produced less residual bone graft
      material, indicating more rapid turnover of bone graft. All treatment modalities
      achieved a significant amount of new vital bone at 8 weeks postextraction.

PMID- 24683579
TI  - A finite element study of short dental implants in the posterior maxilla.
AB  - PURPOSE: Elevated bite forces and reduced bone densities and dimensions
      associated with posterior regions of the maxilla cause relatively high failure
      rates when short dental implants are placed to substitute missing teeth. This
      study uses the finite element method to evaluate four distinctly different short
      implant designs (Bicon, Neodent, Nobel Biocare, and Straumann) for their
      influences on the von Mises stress characteristics within the posterior maxilla.
      MATERIALS AND METHODS: Finite element models of the supporting bone and tooth
      crowns are developed based on computed tomography data, and implant geometries
      are obtained from manufacturers' catalogs. The finite element models are meshed
      using three-dimensional hexahedral and wedge-shaped brick elements. Assumptions
      made in the analyses are: linear elastic material properties for bone, 50%
      osseointegration between bone and implant, and crown height-implant length ratio
      of 2:1. RESULTS: Bicon's neck indentation produced reduced stress in the cortical
      bone when compared with the Nobel Biocare and Straumann systems. The increased
      taper of the Neodent design decreased the stress level in cancellous bone. Nobel
      Biocare's rounded thread crest and reduced thread pitch produced a smoother
      stress profile. Straumann's increased thread pitch produced elevated stress in
      the cancellous bone. Generally, stresses were concentrated in the crestal bone
      region around the implant neck, attributable to the inclined nature of the
      masticatory force. CONCLUSION: Nobel Biocare and Bicon systems are recommended
      for use in type 4 cancellous and cortical bone, respectively.

PMID- 24683580
TI  - A three-dimensional finite element analysis of short dental implants in the
      posterior maxilla.
AB  - PURPOSE: This study evaluated the biomechanical behavior of short dental implants
      with different heights of residual bone and compared it with that of standard
      dental implants in 13 mm or less of residual bone by means of finite element
      analysis. MATERIALS AND METHODS: It was assumed that the maxillary first and
      second molars had been replaced with splinted cast gold crowns supported by two
      implants. A total of five posterior edentulous maxilla models were fabricated
      with various residual bone heights (13 mm, 7 mm, 6 mm, 5 mm, and 4 mm). Residual
      bone height was 13 mm in the group 1 model (control) and 7, 6, 5, and 4 mm in
      group 2-1, group 2-2, group 2-3, and group 2-4 models, respectively. In the group
      1 model, two identical implants (4.5 * 11 mm) and abutments (6 * 2.5 mm) were
      placed. In the group 2 models, two identical wide/short implants (6 * 5.7 mm) and
      abutments (6 * 5 mm) were placed. Off-axis (30 degrees) loading of 187 N was
      applied to the central fossae of the two implant-supported crowns. RESULTS:
      Maximum von Mises stresses in crestal cortical bone were lower in group 2 models
      than in the group 1 model. CONCLUSION: This numeric simulation confirmed that,
      without maxillary sinus bone graft, more effective stress distribution could be
      obtained in 4, 5, 6, or 7 mm of residual bone with short dental implants than in
      13 mm of residual bone with standard dental implants.

PMID- 24683581
TI  - Liquid nitrogen-treated autogenous dentin as bone substitute: an experimental
      study in a rabbit model.
AB  - PURPOSE: Different forms of dentin, including untreated, undemineralized,
      demineralized, boiled, or mixed with other materials, have been evaluated for
      efficacy as bone substitutes. However, the effects of application of liquid
      nitrogen-treated dentin for bone grafting remain unknown. The objective of this
      study was to chronologically evaluate bone healing following grafting with liquid
      nitrogen-treated dentin in a rabbit model. MATERIALS AND METHODS: Autogenous
      dentin treated with liquid nitrogen at -196 degrees C for 20 minutes was used. In
      16 New Zealand White rabbits, a bone defect (5 mm in diameter) was created in
      each femur and randomly grafted with either autogenous dentin (experimental
      group) or autogenous bone grafts (positive control). In another four rabbits
      (negative control), a similar defect in each femur was left empty. The rabbits
      were sacrificed at 2, 4, 8, and 12 weeks. Explants of grafted sites were
      harvested for histologic and histomorphometric analysis. RESULTS: At 2 and 4
      weeks in both the experimental and positive control groups, accelerated formation
      of new bone was observed, which was undergoing remodeling at 8 and 12 weeks. The
      mean new bone score was higher in the experimental than in the negative control
      groups, but this was not statistically significant. CONCLUSION: The present
      results demonstrated that liquid nitrogen-treated autogenous dentin has both
      osteoconductive and osteoinductive properties and therefore has potential as a
      bone substitute.

PMID- 24683582
TI  - Molecular assessment of osseointegration in vitro: a review of current
      literature.
AB  - This paper presents the results of a structured review of the literature
      concerning in vitro molecular assessment of osseointegration at the level of cell
      surface topography interactions. A search of the electronic databases was
      performed up to and including November 2010, with 320 articles meeting the
      inclusion criteria. Characteristics of the included in vitro reports were model
      systems used, genes examined, techniques used for molecular assessment of the
      osseointegration process, and wide gene expression profiling studies. There
      exists a growing body of in vitro evidence to support a role for surface
      topography in the direct influence of cellular phenotypes as related to the
      process of osseointegration. Most recently, functional or mechanistic studies
      have provided evidence that particular topographic cues can be specifically
      integrated among the many extracellular signals received by the cell in its
      signal transduction network. Such investigations begin to define linkages between
      the character of the implant surface and adherent cellular responses, including
      cells from extravasated blood (eg, platelets) and of the immune system (eg,
      monocytes). In vitro studies involving cell culture on endosseous implant-related
      biomaterials offer important and beneficial insight into the clinical control of
      the implant-bone interface.

PMID- 24683583
TI  - Translational research: The CD34+ cell is crucial for large-volume bone
      regeneration from the milieu of bone marrow progenitor cells in craniomandibular
      reconstruction.
AB  - PURPOSE: This study investigated the role of the bone marrow-derived CD34+ cell
      in a milieu of osteoprogenitor cells, bone marrow plasma cell adhesion molecules,
      recombinant human bone morphogenetic protein (rhBMP), and a matrix of crushed
      cancellous allogeneic bone in the clinical regeneration of functionally useful
      bone in craniomandibular reconstructions. The history and current concepts of
      bone marrow hematopoietic stem cells and mesenchymal stem cells are reviewed as
      they relate to bone regeneration in large continuity defects of the mandible.
      MATERIALS AND METHODS: Patients with 6- to 8-cm continuity defects of the
      mandible with retained proximal and distal segments were randomized into two
      groups. Group A received an in situ tissue-engineered graft containing 54 +/- 38
      CD34+ cells/mL along with 54 +/- 38 CD44+, CD90+, and CD105+ cells/mL together
      with rhBMP-2 in an absorbable collagen sponge (1 mg/cm of defect) and crushed
      cancellous allogeneic bone. Group B received the same graft, except the CD34+
      cell concentration was 1,012 +/- 752 cells/mL. The results were analyzed
      clinically, radiographic bone density was measured in Hounsfield units (HU), and
      specimens were analyzed histomorphometrically. RESULTS: Forty patients
      participated (22 men and 12 women; mean age, 57 years). Eight of 20 group A
      patients (40%) achieved the primary endpoint of mature bone regeneration, whereas
      all 20 group B patients (100%) achieved the primary endpoint. CD34+ cell counts
      above 200/mL were associated with achievement of the primary endpoint. Bone
      density was lower in group A (424 +/- 115 HU) than in group B (731 +/- 98 HU).
      Group A bone showed a mean trabecular bone area of 36% +/- 10%, versus 67% +/-
      13% for group B. CONCLUSIONS: The CD34+ cell functions as a central signaling
      cell to mesenchymal stem cells and osteoprogenitor cells in bone regeneration.
      The mechanism of bone marrow-supported grafts requires a complete milieu to
      regenerate large quantities of functionally useful bone. CD34+ cell counts in a
      concentration of at least 200/mL in composite grafts are directly correlated to
      clinically successful bone regeneration.

PMID- 24683584
TI  - Stem cell research: applicability in dentistry.
AB  - In the face of extraordinary advances in the prevention, diagnosis, and treatment
      of human diseases, the inability of most tissues and organs to repair and
      regenerate after damage is a problem that needs to be solved. Stem cell research
      is being pursued in the hope of achieving major medical breakthroughs. Scientists
      are striving to create therapies that rebuild or replace damaged cells with
      tissues grown from stem cells that will offer hope to people suffering from
      various ailments. Regeneration of damaged periodontal tissue, bone, pulp, and
      dentin is a problem that dentists face today. Stem cells present in dental pulp,
      periodontal ligament, and alveolar bone marrow have the potential to repair and
      regenerate teeth and periodontal structures. These stem cells can be harvested
      from dental pulp, periodontal ligament, and/or alveolar bone marrow; expanded;
      embedded in an appropriate scaffold; and transplanted back into a defect to
      regenerate bone and tooth structures. These cells have the potential to
      regenerate dentin, periodontal ligament, and cementum and can also be used to
      restore bone defects. The kind of scaffold, the source of cells, the type of in
      vitro culturing, and the type of surgical procedure to be used all require
      careful consideration. The endeavor is clearly multidisciplinary in nature, and
      the practicing dental surgeon has a critical role in it. Playing this role in the
      most effective way requires awareness of the huge potential associated with the
      use of stem cells in a clinical setting, as well as a proper understanding of the
      related problems.

PMID- 24683585
TI  - The use of free fat tissue transfer from the buccal fat pad to obtain and
      maintain primary closure and to improve soft tissue thickness at bone-augmented
      sites: technique presentation and report of case series.
AB  - PURPOSE: Atrophic ridges usually have both hard and soft tissue shortages, and
      bone augmentation can make soft tissue closure difficult. The aim of this case
      series is to present a new method utilizing transfer of free fat tissue grafts
      (FFG) from the buccal fat bad (BFP) during bone augmentation to enhance immediate
      primary soft tissue closure and improve long-term soft tissue thickness and
      quality at the recipient site. MATERIALS AND METHODS: Patients with moderate to
      severe ridge atrophy in different regions of the jaws were treated over a 4-year
      period with bone augmentation and FFG. The BFP was the donor site for the FFG.
      Patients were examined clinically and radiographically (periapical) every 2
      weeks. At 4 months, computed tomography was performed to evaluate the bone gain.
      Reentry was performed after 4 to 5 months to evaluate the soft tissue, obtain
      specimens for histologic examination, and insert implants. RESULTS: Twenty
      patients (18 women, 2 men; mean age 43 years) were followed for 4 to 42 months
      and received 92 implants in the augmented sites. The healing process was
      uneventful, with minimal morbidity. Bone volume increased by 4 to 8 mm
      horizontally and 3 to 6 mm vertically. Thick soft tissue was obtained at the
      recipient sites and around the dental implants, and histologic specimens showed
      that the FFG was replaced by fibrous tissue. CONCLUSIONS: Harvesting of the FFG
      from the BFP is a simple procedure with minor complications, and manipulation and
      handling of the graft are easy. The FFG enhances primary soft tissue closure of
      augmented bone, prevents dehiscences, improves long-term soft tissue thickness,
      and mimics the attached gingiva in its fibrous healing.

PMID- 24683586
TI  - Secondary stabilization of maxillary m-4 treatment with unstable implants for
      immediate function: biomechanical considerations and report of 10 cases after 1
      year in function.
AB  - PURPOSE: Primary stability of dental implants, particularly when they are placed
      into immediate function in the maxilla, has been thought to be required. An
      alternative to primary stability is secondary stabilization, which can be
      obtained by a four-implant distribution pattern using 30-degree angulations for
      all four implants in the so-called "M-4" treatment scheme in combination with
      cross-arch stabilization from a prosthesis. If successful, the use of these two
      measures brings into question whether or not primary stability is required for
      immediate function in the maxilla. MATERIALS AND METHODS: Patients were treated
      with the M-4 implant scheme with immediate function, despite the instability of
      at least one of the four implants. Instability was defined as less than 15 Ncm of
      insertion torque and palpable mobility, and an average anteroposterior spread of
      15 mm between each implant was sought. The patients were followed for 1 year.
      RESULTS: Ten patients were treated with a total of 40 implants. Composite
      insertion torque of the four implants was less than 100 Ncm in half of the
      patients; the average anteroposterior spread was 15.6 mm. After 1 year, no
      implants had been lost, and bone levels around all implants were at or near
      operative levels. There were no failures of provisional or definitive prostheses.
      CONCLUSIONS: M-4 distribution of implants with an average of 15 mm of
      anteroposterior spread and cross-arch stabilization did not require that all four
      implants had high insertion torque; in fact, all mobile implants stabilized and
      osseointegrated under these conditions.

PMID- 24683587
TI  - Topical application of slow-release simvastatin as a bone substitute in bone
      defects in the rat tibia: a pilot study.
AB  - PURPOSE: It is hypothesized that local application of statins positively affects
      bone formation. The aim of this study was to evaluate the potential effect of
      topical slow-release simvastatin as a bone substitute on the healing of bone
      defects in rat tibia. MATERIALS AND METHODS: Granules of slow-releasing
      hydroxypropyl methylcellulose, with or without simvastatin, were inserted into
      critical-size defects in the tibiae of 16 rats (8 in the study group, 8 in the
      control group). Bone static and dynamic histomorphometric variables were examined
      at 2, 4, 6, and 8 weeks postsurgery. RESULTS: All indices examined in the study
      group indicated improved healing relative to the control group, although
      statistical significance was not demonstrated for all variables. In the static
      histomorphometric analysis, osteoid thickness and volume were significantly
      higher in the study group, but the fraction of trabecular surface covered with
      active osteoblasts, the fraction of trabecular surface covered with osteoid, and
      total calcified bone volume were not significantly higher in the experimental
      group. In the dynamic histomorphometric analysis, the mineral apposition rate,
      determined by time-repeated calcein labeling, was significantly higher in the
      study group than in the control group. Experimental time and dosage effects were
      observed for most bone values in the study group. CONCLUSION: The findings
      indicate that topical application of simvastatin for the treatment of bone
      defects enhances the process of healing. Dosage and the methodology of
      administration require further calibration.

PMID- 24683588
TI  - A decade of bisphosphonate bone complications: what it has taught us about bone
      physiology.
AB  - While the AIDS epidemic of the 1980s taught the medical and dental professions
      much about immune cells and the immune system's cellular relationships, the
      bisphosphonate-induced osteonecrosis epidemic of the past decade has taught these
      same professions much about bone turnover, bone cell cross talk, the response and
      functional relationship of bone cells to loading, and drug effects on cellular
      dynamic relationships. The present article explores the literature as well as
      both evidence- and experience-based data to discuss known bone pathologies and
      physiologic mechanisms as well as uncover new findings: (1) bone remodeling is
      the mechanism by which bone adapts to loading stresses, termed either bone
      modeling or Wolff's law, and it is also the mechanism for bone renewal; (2)
      osteoclastic bone resorption triggers bone renewal at a rate of about 0.7%/day by
      its release of growth factors; (3) bisphosphonates prevent the renewal of old and
      injured bone, thus making it brittle and more likely to fracture over time; (4)
      bisphosphonates have a half-life in bone of 11 years because of their
      irreversible binding to bone via their central carbon atom; (5) when administered
      intravenously, bisphosphonate loads bone and accumulates in bone 142.8 times
      faster than when administered orally; (6) osteoclastic resorption of
      bisphosphonate-loaded bone results in osteoclast death in which the cell bursts,
      releasing the bisphosphonate molecules to reenter the local bone or bone marrow
      in a re-dosing effect; (7) endosteal osteoblasts are dependent on the
      osteoclastic resorption/growth factor release/new bone formation mechanism of
      bone renewal, whereas periosteal osteoblasts are not; and (8) it is likely that
      endosteal osteoblasts and periosteal osteoblasts have different cell membrane
      receptors and arise from separate embryologic niches.

PMID- 24683589
TI  - Rapid-prototype titanium bone forms for vertical alveolar augmentation using bone
      morphogenetic protein-2: design and treatment planning objectives.
AB  - Reconstruction of complex maxillofacial defects where the use of bone
      morphogenetic protein-2 composite grafts may be preferred can be done using
      perforated titanium shells or forms that confine the graft material and
      simultaneously establish the desired shape of the augmentation without resorting
      to autogenous block bone grafting. Reported here is a method for creation of
      rapid-prototype titanium bone forms, which was developed from a software program,
      to reproduce bone morphology precisely. The technique and treatment planning
      objectives are elucidated, especially with regard to complex vertical
      augmentations.

PMID- 24683590
TI  - Biomechanics and peri-implantitis: The effect of a subcrestal wing-thread to
      decrease alveolar crestal bone strain. theory, finite element analysis, and
      clinical application.
AB  - PURPOSE: This study used finite element analysis and a clinical case example to
      test the hypothesis that a wing-thread placed 4 mm below the top of an implant
      would decrease crestal bone loss in function. MATERIALS AND METHODS: Finite
      element analysis was used to compare standard and wing-thread implants subjected
      to axial and off-axis forces based on the hypothesis that decreasing bone strain
      at the alveolar crestal margin improves peri-implant bone stability. A clinical
      case example of the wing-thread implant was followed for 30 months. RESULTS:
      Stress concentration was diminished at the crest when a wing-thread was used
      compared to a standard implant body. Ninety-degree lateral forces were diminished
      by a factor of 10 in the wing-thread implant. A patient followed for 30 months
      showed stable bone levels around the wing-thread implants. CONCLUSION: The wing
      thread hypothesis appears to have some support for increasing bone stability
      based on finite element analysis and early clinical results.

PMID- 24683591
TI  - Evaluation of a commercial primer for bonding of zirconia to two different resin
      composite cements.
AB  - PURPOSE: To evaluate the effects of a commercial zirconia primer (Choice or RelyX
      Unicem) on shear bond strength (SBS) of two different resin composite cements -
      Choice (a conventional bis-GMA-based resin cement) and RelyX Unicem (self
      adhesive resin cement) - to zirconia. MATERIALS AND METHODS: Zirconia blocks were
      manufactured and randomly divided into 5 main groups (n = 20) that received
      surface treatments and cements as follows: no surface treatment, Choice and RelyX
      Unicem (groups C and U, resp.); tribochemical silica coating followed by
      silanization, Choice (group SSC); application of a zirconia primer, Choice and
      RelyX Unicem (groups ZC and ZU, resp.). Light-curing composite resin cylinders
      were prepared and bonded on the prepared zirconia blocks using the two different
      resin cements. Half of the specimens in each group were stored in water for 24 h,
      and half were aged by 50 days of water storage followed by thermocycling (12,000
      cycles between 5 degrees C and 55 degrees C). Thereafter, all of them were
      submitted to the SBS test. Fourier transmission infrared (FT-IR) spectrum
      analysis and gas mass spectrometry (MS) analysis were adopted for
      characterization of the zirconia primer. RESULTS: Statistical analysis of the SBS
      test showed that group C presented the lowest SBS values and group SSC the
      highest (p < 0.01). Artificial aging exerted no influence on the SBS of groups U,
      SSC, ZC, or ZU. FT-IR analysis suggested that benzene rings and carboxylic groups
      exist in the zirconia primer. MS analysis detected that 2-hydroxyethyl
      methacrylate, triethylamine, ethyl-4-dimethylaminobenzoate, ethanol, and water
      are contained in the primer. CONCLUSION: The zirconia primer and self-adhesive
      resin cement increased the SBS of zirconia.

PMID- 24683592
TI  - Effect on push-out bond strength of glass-fiber posts functionalized with
      polydopamine using different adhesives.
AB  - PURPOSE: To evaluate the push-out bond strengths of prefabricated glass-fiber
      posts (Beijing Oya Biomaterials) with polydopamine functionalized to root dentin
      using two different resin cements (Paracore and RelyX Unicem) in different root
      regions (cervical, middle, and apical). MATERIALS AND METHODS: Forty extracted
      human, single-rooted teeth were endodontically treated and a 9-mm post space was
      prepared in each tooth with post drills provided by the manufacturer. Specimens
      were then randomly assigned into four groups (n = 10 per group), depending on the
      adhesive system and post surface treatment used: group IA (Paracore +
      polydopamine); group IB (Paracore + control); group IIA (RelyX Unicem +
      polydopamine); group IIB (RelyX Unicem + control). Following post cementation,
      the specimens were stored in distilled water at 37 degrees C for 7 days. The push
      out test was performed using a universal testing machine (0.5 mm/ min), and the
      failure modes were examined with a stereomicroscope. Data were statistically
      analyzed using twoway ANOVA (p = 0.05). RESULTS: Bond strengths (mean +/- SD)
      were: 7.909 +/- 3.166 MPa (group IA), 4.675 +/- 2.170 MPa (group IB), 8.186 +/-
      2.766 MPa (group IIA), 4.723 +/- 2.084 MPa (group IIB). The bond strength of
      polydopamine groups was significantly higher than one of the control groups (p <
      0.0001). No significant difference was found in the micro push-out bond strengths
      between the two resin cement groups or the root regions (p > 0.05).
      Stereomicroscopic analysis showed a higher percentage of adhesive than cohesive
      failures in all groups. CONCLUSION: Surface polydopamine functionalization was
      confirmed to be a reliable method for improving the bond strength of resin luting
      agents to fiber posts. The bond strength of Paracore to fiber posts was not
      significantly different from that of RelyX Unicem, and considering its convenient
      application, Paracore can be recommended.

PMID- 24683593
TI  - Replacing HEMA with alternative dimethacrylates in dental adhesive systems:
      evaluation of polymerization kinetics and physicochemical properties.
AB  - PURPOSE: To evaluate the mechanical and physical properties of experimental HEMA
      containing and HEMA-free resin adhesives. MATERIALS AND METHODS: Experimental
      HEMA-free adhesives containing alternative dimethacrylates (bis-EMA 10 [B10], bis
      EMA 30 [B30], PEG 400 [P400], PEG 1000 [P1000], PEG 400 UDMA [UP400]) were
      formulated and compared with a HEMA-containing adhesive (control). The adhesives
      were characterized by rheological analysis, polymerization kinetics (PK), water
      sorption (WS), and solubility (SL) tests. Flexural strength (FS) and flexural
      modulus (E) tests were performed under dry or wet conditions (distilled water or
      70% ethanol solution). One-way and two-way ANOVA as well as Tukey's test were
      used to evaluate differences between groups (p < 0.05). RESULTS: The control
      group showed the lowest viscosity and was the only one with a degree of
      conversion lower than 50%. The control and the P1000 adhesive showed the
      statistically significantly highest WS (p < 0.05). The control and the UP400
      adhesive showed the highest FS and E, and the dry-stored specimens showed more
      improved mechanical strength than did the wet-stored specimens (p < 0.05).
      CONCLUSION: The physicomechanical properties of some of the HEMA-free adhesives
      were substantially improved when compared with those of the control, indicating
      that they could be potential monomers for the development of HEMA-free adhesive
      systems.

PMID- 24683594
TI  - Effect of intermediate adhesive resin and flowable resin application on the
      interfacial adhesion of resin composite to pre-impregnated unidirectional S2
      glass fiber bundles.
AB  - PURPOSE: This study evaluated the effect of either an intermediate application of
      adhesive resin or flowable resin application on the adhesion of particulate
      filler composite (PFC) to glass fiber-reinforced composite (FRC). MATERIALS AND
      METHODS: Unidirectional, pre-impregnated S2-glass fiber bundles (Dentapreg)
      (length: 40 mm; thickness: 0.5 mm) were obtained (N = 30, n = 10 per group) and
      secured in translucent silicone material with the adhesion surface exposed and
      photopolymerized. They were randomly divided into 3 groups for the following
      adhesion sequence: A) FRC+PFC, B) FRC+intermediate adhesive resin+PFC, C)
      FRC+flowable resin+PFC. The PFC was applied in a polyethylene mold onto the FRC
      and photopolymerized. PFCs were debonded from the FRC surface using shear bond
      test in a universal testing machine (1 mm/min). After debonding, all specimens
      were analyzed using scanning electron microscopy to categorize the failure modes.
      The data were statistically analyzed using one-way ANOVA and Tukey's tests (alpha
      = 0.05). RESULTS: A significant difference was observed between the groups (p <
      0.05). The highest mean bond strength value was obtained with the application of
      an intermediate layer of adhesive resin (group B: 19.4 +/- 1.1 MPa) (p < 0.05)
      followed by group A (14.1 +/- 0.6 MPa) and group C (10.4 +/- 0.8 MPa), which were
      also significantly different from one another (p < 0.05). Group A exclusively
      presented a combination of partial cohesive failure in the PFC and adhesive
      failure between the FRC and PFC. While group B showed large cohesive defects in
      the FRC, in group C, only small cohesive failures were observed in the FRC.
      CONCLUSION: Based on the highest mean bond strength and the large cohesive
      failures within the FRC, application of an intermediate layer of adhesive resin
      on the S2-glass FRC surface prior to incremental build up of the PFC seems to be
      compulsory.

PMID- 24683595
TI  - Sorption and solubility of self-etching adhesives immersed in organic acids
      present in oral biofilm.
AB  - PURPOSE: This study evaluated the sorption and solubility of self-etching
      adhesive systems after immersion in distilled water, lactic acid, and propionic
      acid. MATERIALS AND METHODS: Specimens of 2 two-step (P90 System Adhesive [P90],
      Clearfil SE Bond [CSE]) and 1 single-step (Adper Easy One [AEO]) adhesive systems
      were prepared and divided into 4 groups: P90 primer ( P90-P), P90 bond (P90-B),
      AEO, and CSE bond (CSE-B). Specimens were placed in a desiccator and weighed
      daily until achieving a constant mass (m1). The specimens (n = 5) were then
      immersed in the respective media and weighed until a achieving a constant mass
      (m2). The specimens were again desiccated (m3). Sorption and solubility data were
      analyzed with two-way ANOVA and Turkey's test. Specimens were also observed using
      SEM without immersion, after 24 h, and at the end of the respective total time of
      immersion. RESULTS: For all immersion media, the highest sorption values were
      obtained for AEO and P90-P, followed by CSE-B and P90-B, which presented the
      lowest sorption. The time required for adhesives to absorb the solutions was: 11
      to 19 days for P90-P, 12 to 13 days for P90-B, 15 to 19 days for AEO, and 14 to
      18 days for CSE-B. The highest values of solubility were shown for AEO and P90-P
      in all immersion media. In water and propionic acid, the adhesives with the
      lowest solubility values were CSE-B and P90-B. CSE-B had the lowest solubility in
      lactic acid. CONCLUSION: The greatest surface degradation was observed after each
      respective total time of immersion. AEO specimens presented more evident surface
      degradation and the highest sorption and solubility.

PMID- 24683596
TI  - Imaging mass spectrometry of a mouse brain by tapping-mode scanning probe
      electrospray ionization.
AB  - Methods for ambient sampling and ionization enable chemical information to be
      obtained with minimal sample preparation. Also, imaging mass spectrometry (IMS)
      enables the spatial distribution of multiple components to be determined by a
      single measurement. Here, we report an improved method of tapping-mode scanning
      probe electrospray ionization (t-SPESI) for ambient sampling and ionization in
      which probe oscillation is stabilized by using a piezo actuator. We demonstrate
      negative-mode IMS of a mouse coronal brain section and show that, compared with
      desorption electrospray ionization, t-SPESI provides unique features in the mass
      spectra: signal enhancement of fatty acid and lipids, and formation of
      multivalent ions tentatively assigned to gangliosides. These results would
      indicate the capability for the generation of multiple types of ions with t
      SPESI. 

PMID- 24683598
TI  - Morphology, molecular stacking, dynamics and device performance correlations of
      vacuum-deposited small-molecule organic solar cells.
AB  - The "all carbon" organic solar cells (OSCs) based on the homocyclic molecule
      tetraphenyldibenzoperiflanthene (DBP) as a donor and C60 as an acceptor were
      comprehensively characterized. The optimized planar-mixed heterojunction device
      with a DBP:C60 mixture ratio of DBP : C60 (1 : 2) exhibited a power conversion
      efficiency of 4.47%. To understand why DBP possesses such advantageous
      characteristics, the correlations of the morphology, molecular stacking, carrier
      dynamics and performance of DBP:fullerene-based devices have been systematically
      studied. First, the face-on stacked DBP molecules could enhance both the
      absorption of light and the charge carrier mobility. Second, DBP : C60 (1 : 2)
      thin films with optimized domain sizes and partially interconnected acceptor
      grains led to the most balanced carrier mobility and the lowest bimolecular
      recombination in devices. Finally, the DBP molecules were found to stack closely
      using grazing incidence wide-angle X-ray scattering measurements, with a pi-pi
      stacking spacing of 4.58 A, indicating an effective molecular orbital overlap in
      DBP. The study not only reveals the promising characteristics of DBP as a donor
      in OSCs but the clear correlations of the thin-film nano-morphology, molecular
      stacking, carrier mobility and charge recombination found here could also provide
      insights into the characterization methodology and optimization of the small
      molecule OSCs. 

PMID- 24683599
TI  - High-nuclearity silver(I) cluster-based coordination polymers assembled with
      multidentate oligo-alpha-heteroarylsulfanyl ligands.
AB  - Two novel coordination polymers [Ag16(SO4)8][Ag4(SO4)2]3(L1)12.nH2O (n = 72) (1)
      and [Ag10(SO4)5(L2)4(H2O)2].8H2O (2) based on conformationally variable oligo
      alpha-heteroarylsulfanyl ligands 2-(pyrazin-2-ylthio)-6-(pyridin-2
      ylthio)pyrazine (L1) or 2,6-bis(pyrazin-2-ylthio)pyrazine (L2) and sulfate
      templated high-nuclearity Ag(I) clusters as structure-building units (SBUs) have
      been synthesized under mild conditions. Single-crystal X-ray analysis showed that
      complex 1 exhibits a porous three-dimensional framework containing Ag16(SO4)8 and
      Ag4(SO4)2 SBUs that are interconnected by L1 ligands, whereas 2 has a much denser
      network constructed from Ag10(SO4)5 SBUs and L2 linkers. To our knowledge, the
      Ag16(SO4)8 cluster core found in 1 is the largest sulfate-based polynuclear SBU
      in coordination polymers, and the 14-connected Ag10(SO4)5 in 2 is the highest
      connectivity Ag(I) cluster SBU reported to date. These two complexes were fully
      characterized by infrared spectroscopy, elemental analysis, powder X-ray
      diffraction, thermogravimetric analysis and differential scanning calorimetry.

PMID- 24683600
TI  - Effects of crystalline phase and morphology on the visible light photocatalytic
      H2-production activity of CdS nanocrystals.
AB  - Visible light photocatalytic H2-production from aqueous solutions is of great
      importance for its potential application in converting solar energy into chemical
      energy. In this study, a series of CdS nanostructures with different contents of
      wurtzite (WZ) and zinc blende (ZB) phases were successfully synthesized by a
      simple solvothermal route in an ethylenediamine and ethylene glycol mixed
      solution. The solvent volume ratio of ethylenediamine in the mixed solution (R)
      exhibited an obvious influence on the crystalline phase and morphology of the
      resulting CdS products. With increasing R, the percentage of wurtzite first
      increased and then decreased, whilst the morphology changed from nanoparticles to
      multi-armed nanorods, and finally to long rods and sheets. The prepared multi
      armed CdS nanorod samples showed especially high and stable photocatalytic H2
      production activity with Pt (0.25 wt%) as a co-catalyst and lactic acid aqueous
      solution as a sacrificial reagent under visible light irradiation. The optimized
      CdS nanorods with the highest percentage (64%) of the WZ phase exhibited a high
      H2-production rate of 231.4 MUmol h(-1) (about 16.6 times higher than that of CdS
      nanoparticles with a low percentage (38.4%) of WZ CdS) and with a quantum
      efficiency (QE) of 28% at 420 nm. This high photocatalytic H2-production activity
      could be attributed to the results of the positive synergistic effects of the
      hexagonal WZ phase and morphology of multi-armed nanorods. 

PMID- 24683601
TI  - Siderophore-promoted dissolution of chromium from hydroxide minerals.
AB  - Biomolecules have significant impacts on the fate and transport of contaminant
      metals in soils and natural waters. Siderophores, Fe(iii)-binding agents that are
      exuded by microbes and plants, may form strong complexes with and promote the
      dissolution of contaminant metal ions, such as Co(iii), U(iv), or Pu(iv).
      Although aqueous Cr(iii)-siderophore complexes have been recognized in the
      laboratory setting for almost 40 years, few studies have explored interactions of
      siderophores with Cr-bearing minerals or considered their impacts on
      environmental chemistry. To better understand the possible effects of
      siderophores on chromium mobility, we conducted a series of dissolution
      experiments to quantify the dissolution rates of Cr(iii)(OH)3 in the presence of
      hydroxamate, catecholate, and alpha-hydroxycarboxylate siderophores over a range
      of environmentally relevant pH values. At pH = 5, dissolution rates in the
      presence of siderophores are similar to control experiments, suggesting a
      predominantly proton-promoted dissolution mechanism. At pH = 8, the sorption of
      the siderophores desferrioxamine B and rhizoferrin can be modeled by using
      Langmuir isotherms. The dissolution rates for these siderophores are proportional
      to the surface concentrations of sorbed siderophore, and extended X-ray
      absorption fine structure spectra of dissolution products indicates the formation
      of Cr(iii)HDFOB(+) and Cr(iii)rhizoferrin(3-) complexes, suggesting a ligand
      promoted dissolution mechanism at alkaline pH. Because siderophores promote
      Cr(iii)(OH)3 dissolution at rates similar in magnitude to those of iron
      hydroxides and the resulting Cr(iii)-siderophore complexes may be persistent in
      solution, siderophores could potentially contribute to the mobilization of Cr in
      soils and sediments where it is abundant due to geological or anthropogenic
      sources. 

PMID- 24683602
TI  - Extracts from Brassica oleracea L. convar. acephala var. sabellica inhibit TNF
      alpha stimulated neutrophil adhesion in vitro under flow conditions.
AB  - The beneficial effects of vegetables such as leafy cabbage (Brassica oleracea) on
      health are attributed to their anti-oxidative and anti-inflammatory potential.
      Therefore, we investigated whether curly kale extracts affect cytokine induced
      expression of endothelial cell adhesion molecules as well as the adhesion of
      leukocytes to endothelial cells depending on their polyphenol content and
      composition. Curly kale leaves were extracted applying two solvents with
      different polarities (methanolic extracts (ME) and aqueous water extracts (WE)).
      The anti-oxidant capacity (TEAC-assay (Trolox Equivalent Antioxidant Capacity)),
      the polyphenol content and the composition were determined colorimetrically. The
      anti-inflammatory effects were measured in vitro using human umbilical vein
      endothelial cells (HUVECs). HUVECs were pre-incubated with extracts for 24 h and
      thereafter stimulated for 5 h with TNF-alpha (10 ng mL(-1)). Finally, the
      expression of cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 was
      determined by semi-quantitative RT-PCR and leukocyte adhesion was observed using
      a flow adhesion assay. ME have the highest anti-oxidant activity (ME, 66.5 +/-
      10.9 vs. WE, 45.5 +/- 6.7 mmol L(-1) TEAC), polyphenol (ME, 25.8 +/- 2.4. vs. WE,
      10.8 +/- 1.8 mmol L(-1) GAE), flavonoid (ME, 17.9 +/- 1.7 vs. WE, 5.3 +/- 2.7
      mmol L(-1) RE) and flavonol concentrations (ME, 5.8 +/- 0.6 vs. WE, 2.1 +/- 0.5
      mmol L(-1) RE) in comparison to WE. The TEAC and polyphenol values well
      correlated with their effect on cell adhesion. Using 10% ME, reduced adhesion of
      leukocytes to HUVECs was measured (36 +/- 13%), whereas 10% WE reduced cell
      adhesion to 57 +/- 5% of the TNF-alpha stimulated controls (100%). Concomitant
      with the reduced leukocyte cell adhesion in the flow assay, ME and WE
      significantly reduced the TNF-alpha induced expression of cell adhesion
      molecules: E-selectin (ME, 51.3 +/- 10.7 vs. WE, 76.3 +/- 11.9%), ICAM-1 (ME,
      74.6 +/- 10.2 vs. WE, 81.6 +/- 7.9%) and VCAM-1 mRNA expression (ME, 35.0 +/-
      14.0 vs. WE, 76.6 +/- 7.9%) were significantly reduced with 10% extracts. The
      inhibitory effect of water and methanolic soluble ingredients of curly kale
      leaves on cell-cell interaction and gene expression events supports their health
      promoting effect under inflammatory conditions. 

PMID- 24683603
TI  - Out-of-equilibrium biomolecular interactions monitored by picosecond fluorescence
      in microfluidic droplets.
AB  - We developed a new experimental approach combining Time-Resolved Fluorescence
      (TRF) spectroscopy and Droplet Microfluidics (DMUF) to investigate the relaxation
      dynamics of structurally heterogeneous biomolecular systems. Here DMUF was used
      to produce with minimal material consumption an out-of-equilibrium, fluorescently
      labeled biomolecular complex by rapid mixing within the droplets. TRF detection
      was implemented with a streak camera to monitor the time evolution of the
      structural heterogeneity of the complex along its relaxation towards equilibrium
      while it propagates inside the microfluidic channel. The approach was validated
      by investigating the fluorescence decay kinetics of a model interacting system of
      bovine serum albumin and Patent Blue V. Fluorescence decay kinetics are acquired
      with very good signal-to-noise ratio and allow for global, multicomponent
      fluorescence decay analysis, evidencing heterogeneous structural relaxation over
      several 100 ms. 

PMID- 24683604
TI  - Total hip replacement and the older man: more options than you really need. A
      standard metal-and-plastic joint implant is a reliable, well-tested solution that
      could last a lifetime.

PMID- 24683605
TI  - On call.  Do any of the smoking cessation aids, like gum or patches, work better
      than the others?

PMID- 24683606
TI  - On call.  At my last physical, the doctor did not collect urine tests.  Shouldn't
      that always be part of a physical?

PMID- 24683607
TI  - Acetaminophen safety:  be cautious but not afraid.  Read labels and stick to
      guidelines to prevent this widely used pain and fever remedy from harming your
      liver.

PMID- 24683608
TI  - Sugar: how much is too much? To stay within healthy limits, start retraining your
      brain not to crave sweetened foods and beverages.

PMID- 24683609
TI  - Better health with new digital devices. Technology can link you to your doctor
      via the Internet, helping you to get more effective and more convenient health
      care.

PMID- 24683610
TI  - Screening for lung cancer: are you a candidate for this test?  For those who
      qualify, a low-dose CT scan to look for small tumors may be free of charge. 
      Here's how it works.

PMID- 24683611
TI  - Could cholesterol-lowering drugs cause cataracts?

PMID- 24683612
TI  - No long-term gain from early dementia testing.

PMID- 24683613
TI  - Exercise benefit equals drugs for some health problems.

PMID- 24683614
TI  - Don't let that heartburn go untreated.  You may be risking a condition linked to
      esophageal cancer.

PMID- 24683615
TI  - Top 5 fixes for itchy winter skin.  A humidifier, moisturizer, and lukewarm water
      can help.

PMID- 24683616
TI  - Save money on your prescription medications.  Comparison shopping, assistance
      programs, and prescription price finders can help.

PMID- 24683617
TI  - To treat osteoporosis, Denosumab appears more effective than Zoledronate.
      Denosumab has the advantage in building bone density, and has fewer side effects.

PMID- 24683618
TI  - Knowledge about cataract formation could lead to new treatments.  Encouraging new
      research suggests that scientists may be closer to a means of preventing this all
      too-common condition.

PMID- 24683619
TI  - Genetic reaction to stress may explain many hearts attacks.  An inherited genetic
      flaw appears to increase risk, even in the absence of traditional risk factors.

PMID- 24683620
TI  - Advantage of daily exercise continues to be reaffirmed.  Pick up the pace for
      significant health benefits.

PMID- 24683621
TI  - Pollen allergy linked to a higher risk of blood cancers in women.  Findings
      suggest a possible gender-specific role in chronic stimulation of the immune
      system.

PMID- 24683622
TI  - Lately, I've been having the strangest sensation: I feel like I'm spinning. What
      could this mean? Is it some kind of "condition"?

PMID- 24683623
TI  - What can you tell me about "silent" atrial fibrillation. Are there any risks
      involved?

PMID- 24683624
TI  - I've heard adding nuts to your diet on a regular basis is really good for you.
      Are there any particular nuts that are better than others? And, why are nuts good
      for you?

PMID- 24683625
TI  - Aortic aneurysm.  Safer surgery for bulging abdominal artery.

PMID- 24683626
TI  - Health tips.  Finding balance in Alzheimer's caregiving.

PMID- 24683628
TI  - Zeroing in on a biomarker that may influence muscle mass.

PMID- 24683627
TI  - Mindful medication may cut risk, severity of common cold.

PMID- 24683629
TI  - Immune suppression and infections. Keeping a balance.

PMID- 24683630
TI  - Urinary tract infections in women.  A common concern.

PMID- 24683631
TI  - Happy, healthy feet. Exercises for stability.

PMID- 24683632
TI  - My doctor wants me to use an inhaled steroid for asthma.  Why can't I just use my
      quick-relief inhaler?

PMID- 24683633
TI  - I understand why someone with an underactive thyroid would be fatigued, but I was
      diagnosed with an overactive thyroid and fatigue was my main symptom.  How could
      I be fatigued if I have too much thyroid hormone in my system?

PMID- 24683634
TI  - Abnormal alpha cell function in diabetics response to insulin.
AB  - The extremely high levels of glucagon recently observed in dogs with severe
      alloxan-induced diabetes decline promptly and precipitously to normal as soon as
      exogenous insulin is infused. This suggests that the normal response of the
      pancreatic alpha cell to hyperglycemia requires the presence of circulating
      insulin. To determine if the relative hyperglucagonemia of human diabetics
      responds similarly to insulin repletion, the plasma glucagon response of ten
      adult-type diabetic patients to a large, predominantly carbohydrate meal was
      determined with and without the simultaneous forty-five-minute intravenous
      infusion of glucagon free insulin (0.12 to 0.2 U./kg.). The glucagon response to
      the carbohydrate meal during prompt and super normal hyperinsulinemia resulting
      from the infusion did not differ from that of the control meal, i.e. normal
      suppression of glucagon by hyperglycemia was not restored by the abundance of
      circulating insulin.To determine if still higher plasma levels of insulin would
      overcome the hyposuppressibility of the diabetic alpha cell to hyperglycemia, 0.6
      U. per kilogram per hour of insulin was infused at a constant rate for two hours
      together with 0.6 gm. per kilogram per hour of glucose to prevent
      hypoglycemia.Insulin levels of more than 1,200 MUU. per milliliter were thus
      attained. Under these conditions, plasma glucagon declined from a mean
      preinfusion level of 97 pg./ml. (SEM +/- 11) to a nadir of 75 pg./ml. (SEM +/-
      10) ninety minutes later. This slow, modest, statistically significant (p <
      0.01)decline differed strikingly from the response of eight non diabetic patients
      given intravenous glucose alone; in these subjects, at a comparable level of
      hyperglycemia, glucagon declined from a mean fasting level of 90 pg./ml. (SEM +/-
      8) to 57 pg./ml. (SEM +/- 8) within thirty minutes, despite an insulin rise to
      only 46 MUU./ml.It was concluded that in human diabetics the acute restoration of
      plasma insulin, even to supernormal levels, does not promptly restore to normal
      the alpha cell responsiveness to hyperglycemia. Simple insulin lack may not,
      therefore,adequately explain the alpha cell abnormality in human diabetes.

PMID- 24683635
TI  - A special supplement on women's health. Introduction.

PMID- 24683637
TI  - Animal experimentation in the UK: probing beyond the rhetoric.

PMID- 24683639
TI  - Absence of evidence or evidence of absence? Reply.

PMID- 24683638
TI  - Absence of evidence or evidence of absence?

PMID- 24683644
TI  - Professor Hakan Caner: a life devoted to neurosurgery.

PMID- 24683645
TI  - Reply: To PMID 24093690.

PMID- 24683646
TI  - Reply: To PMID 23672894.

PMID- 24683647
TI  - Using cement plugs in soft tissue infection and osteomyelitis.
AB  - Operative foot and ankle osteomyelitis is challenging for orthopedic surgeons
      because of the area's unique anatomy, high trauma incidence, local and systemic
      disease effects, and often limited space. Standard treatment includes aggressive
      operative debridement with local and systemic antibiotic administration to
      control infection. Dead space management is critical yet technically demanding.
      The authors report a modified antibiotic cement bead therapy technique in which
      antibiotic sticks, minnows, and mushroom-shaped plugs are used to strike a
      balance between the stability of the load-bearing unit and radical removal of
      infection to preserve a functional foot. Three cases are presented.

PMID- 24683648
TI  - Drain technique in elective total joint arthroplasty.
AB  - The authors report a simple technique for effective management of surgical drains
      and their reliable removal in elective hip and knee arthroplasty. Many surgeons
      use surgical drains for elective total hip and knee arthroplasties and instruct
      residents in their use despite limited evidence to support routine use of
      surgical drains in noninfected cases. There are many different types of drains
      and equally varied methods for implantation, monitoring, and removal. Technical
      issues regarding use of closed suction surgical drainage postoperatively deal
      primarily with the questions of when to remove the surgical drain and how to
      manage difficulties with drain removal or breakage.

PMID- 24683649
TI  - Reprocessed arthroscopic shavers: evaluation of sharpness and function in a
      cadaver model.
AB  - This study was designed to test limited arthroscopic shaver reuse following
      reprocessing and to compare the functional performance between new and
      reprocessed arthroscopic shavers in arthroscopic procedures using fresh cadaveric
      knees. A trial using arthroscopic procedures (menisectomy, synovectomy, and
      debridements) was conducted by experienced surgeons using cadaveric knees to
      determine whether the surgeons could correctly identify reprocessed shavers.
      Thirty-nine shavers were tested; the surgeons were given both new and reprocessed
      shavers. Thirteen of the 39 shavers were new and 26 were reprocessed (13 of which
      had also been sharpened). The surgeons were asked to assess whether each shaver
      was new or reprocessed and to indicate whether the shaver was functional or not.
      Cadaveric shavers were subsequently used in an engineering test developed to
      measure shaver blade sharpness. Comparisons in sharpness were made between new
      and reprocessed cadaveric shaver blades. The success rate in identifying
      reprocessed shavers was determined to be 42% (11 of 26), with an upper confidence
      bound of 60%, demonstrating that the ability to detect a reprocessed shaver is no
      better than chance (50%), with a margin of error of 10% (P=.0328). In addition,
      engineering sharpness testing demonstrated that new and reprocessed cadaveric
      blades exhibit equivalent sharpness. Surgeons were unable to distinguish
      reprocessed arthroscopic shavers that passed acceptance tests from new shavers
      based on functional characteristics. This outcome is not unexpected due to the
      fact that engineering testing of shaver blades used in the study indicated that
      they exhibited similar sharpness.

PMID- 24683650
TI  - Orthopedic inpatients' ability to accurately reproduce partial weight bearing
      orders.
AB  - Partial weight bearing is often prescribed for patients with orthopedic injuries.
      Patients' ability to accurately reproduce partial weight bearing orders is
      variable, and its impact on clinical outcomes is unknown. This observational
      study measured patients' ability to reproduce partial weight bearing orders,
      factors influencing this, patients' and physiotherapists' ability to gauge
      partial weight bearing accuracy, and the effect of partial weight bearing
      accuracy on long-term clinical outcomes. Fifty-one orthopedic inpatients
      prescribed partial weight bearing were included. All received standard
      medical/nursing/physiotherapy care. Physiotherapists instructed patients in
      partial weight bearing using the hand-under-foot, bathroom scales, and/or verbal
      methods of instruction. Weight bearing was measured on up to 3 occasions during
      hospitalization using a force-sensitive insole. Factors that had the potential to
      influence partial weight bearing accuracy were recorded. Patients and their
      physiotherapists rated their perception of partial weight bearing accuracy. Three
      month clinical follow-up data were retrieved from medical records. The majority
      of patients (72% or more) exceeded their target load, with mean peak weight
      bearing as high as 19.3 kg over target load (285% of target load). Weight bearing
      significantly increased over the 3 measurement occasions (P<.001) and was
      significantly associated with greater body weight (P=.04). Patients and
      physiotherapists were unable to accurately gauge partial weight bearing accuracy.
      The incidence of clinically important complications at 3 months was 9% and not
      significantly associated with partial weight bearing accuracy during
      hospitalization (P>=.45). Patients are unable to accurately reproduce partial
      weight bearing orders when trained with the hand-under-foot, bathroom scales, or
      verbal methods of instruction.

PMID- 24683651
TI  - Self-designed femoral neck guide pin locator for femoral neck fractures.
AB  - Closed reduction and fixation with 3 cannulated screws is a widely accepted
      surgery for the treatment of femoral neck fractures. However, how to obtain
      optimal screw placement remains unclear. In the current study, the authors
      designed a guide pin positioning system for femoral neck fracture cannulated
      screw fixation and examined its application value by comparing it with freehand
      guide needle positioning and with general guide pin locator positioning provided
      by equipment manufacturers. The screw reset rate, screw parallelism, triangle
      area formed by the link line of the entry point of 3 guide pins, and maximum
      vertical load bearing of the femoral neck after internal fixation were recorded.
      As expected, the triangle area was largest in the self-designed positioning
      group, followed by the general positioning group and the freehand positioning
      group. The difference among the 3 groups was statistically significant (P<.05).
      Anteroposterior and lateral radiographs showed that the screws were more parallel
      in the self-designed positioning group and general positioning group compared
      with the freehand positioning group (P<.05). The screw reset rate in the self
      designed positioning group was significantly lower than that in the general
      positioning group and the freehand positioning group (P<.05). Maximum bearing
      load among the 3 groups was equivalent, showing no statistically significant
      difference (P>.05). The authors' self-designed guide pin positioning system has
      the potential to accurately insert cannulated screws in femoral neck fractures
      and may reduce bone loss and unnecessary radiation.

PMID- 24683652
TI  - Relationship between preservation of the lateral pillar and collapse of the
      femoral head in patients with osteonecrosis.
AB  - It is difficult to predict if and when the femoral head will collapse and whether
      the collapse can be minimized. This study examined the final outcome of early
      stage osteonecrosis of the femoral head (ONFH) using magnetic resonance imaging
      to verify the relationship between preservation of the lateral pillar and
      collapse of the femoral head. A midcoronal section of the femoral head was
      divided into 3 pillars (medial, central, and lateral) on a T1-weighted image.
      According to the site of necrosis on the lateral pillar, the necrosis was divided
      into 3 types: I, the necrosis occupies the central and medial pillars, and the
      lateral pillar is preserved; II, the necrosis partially occupies the lateral
      pillar; and III, the necrosis totally occupies the lateral pillar. One group of
      87 patients (127 hips) with Association for Research on Osseous Circulation
      (ARCO) stage I ONFH underwent nonoperative treatment and were followed for 3 to 8
      years (average, 6.2 years). Another group of 42 patients (72 hips) with ARCO
      stage I ONFH underwent debridement and impacted bone graft and were followed for
      5 to 9 years (average, 7.1 years). In both groups, the more preserved the lateral
      pillar, the less collapse occurred. The authors concluded that whether ONFH
      progressed to collapse is determined by preservation of the lateral pillar. The
      lateral pillar is the keystone for maintaining the sphere of the femoral head and
      its preservation.

PMID- 24683654
TI  - Rigid internal fixation of displaced distal radius fractures.
AB  - Distal radius fractures, the most common long bone fracture, are treated in
      several ways, including closed reduction, percutaneous pinning, external
      fixation, and open reduction and internal fixation. This article presents a
      surgical technique and a series of patients treated with a novel minimally
      invasive intramedullary fixation technique. The implant is a partially flexible
      intramedullary rod that can be locked in a rigid position once it is implanted in
      the bone. An awl and reamer are passed through a starter hole in the radial
      styloid using a 2-cm incision between the 1st and 2nd dorsal compartments. The
      device is then implanted under the articular surface, and the distal end of the
      curved implant is placed down the intramedullary canal of the radius. After
      locking the shaft segment rigidly, screws are placed through the implant under
      the distal radial articular margin to stabilize the fracture site. The sensory
      branches of the radial nerve are retracted during the case. Patients are treated
      in a wrist splint for a short period of time (2 to 4 weeks) depending on fracture
      type. The case examples demonstrate the minimally invasive nature of this
      procedure, the surgical technique, methods of fracture reduction and
      implantation, and surgical outcomes. Radiographic outcomes, postoperative motion,
      postoperative function, and validated outcome measures are demonstrated. This
      minimally invasive technique is ideally suited for distal radial fractures that
      do not involve the articular surface. It is a safe and effective technique that
      can provide excellent results.

PMID- 24683653
TI  - Sensitivity of physical examination versus arthroscopy in diagnosing
      subscapularis tendon injury.
AB  - The purpose of this study was to examine the accuracy of physical examination in
      the detection of subscapularis tendon tears and compare it with the gold standard
      of arthroscopy to determine whether clinical examination can reliably predict the
      presence of subscapularis tendon tears. This was a retrospective analysis of 52
      patients (52 shoulders) who underwent arthroscopic subscapularis tendon repairs
      between September 2008 and April 2012. Positive findings on any combination of
      the belly press, lift-off, and bear hug tests constituted a positive physical
      examination result. There was a positive finding on physical examination in 42 of
      52 patients. The sensitivity of the physical examination as a whole was 81%. The
      literature has shown that the belly press, bear hug, and lift-off tests are
      specific to the subscapularis tendon. To the authors' knowledge, this is the
      first study to evaluate the sensitivity of these 3 separate clinical tests as a
      composite. Knowledge regarding the sensitivity of the subscapularis-specific
      physical examination as a composite can lead practitioners to implement all 3
      components, even when 1 test has a negative finding, thus promoting a more
      thorough physical examination. Because unrepaired subscapularis tendon tears can
      result in poor outcomes in the repair of other rotator cuff tendons, a complete
      physical examination would be beneficial to patients with shoulder pathology. The
      authors conclude that physical examination, when performed consistently by an
      experienced practitioner, can reliably predict the presence of subscapularis
      tendon tears.

PMID- 24683655
TI  - Computer navigation and total knee arthroplasty.
AB  - Research has added evidence in favor of computer-navigated techniques over
      conventional surgery for total knee arthroplasty (TKA). The goal of the current
      meta-analysis was to compare the outcome of outliers in mechanical axis and
      postoperative complications in patients undergoing conventional vs computer
      navigated techniques for TKA. English literature searches were performed in
      PubMed, EMBASE, Web of Science, and the Cochrane Library for studies published
      between January 2002 and August 2012. Randomized, controlled trials comparing
      computer navigation with conventional surgery for the measurement of mechanical
      axes in patients with primary osteoarthritis were considered eligible. Fifteen
      trials were eligible for inclusion. The baseline demographics of 2089 patients
      (computer-navigated=1111; conventional=978) were well matched. Publication bias
      was eliminated using the funnel plot. A mechanical axis of more than 30 degrees 
      was considered to be malalignment and an outlier in limb alignment. A significant
      increase of 16.9 minutes in mean operative time for computer-navigated TKA was
      observed (P=.046). Although patients undergoing computer-navigated TKA had fewer
      outliers in mechanical axis (13.4%) compared with the conventional technique
      (27.4%), the results did not achieve statistical significance (I2=0.0%; P=1.000).
      Fewer complications were observed in patients undergoing computer-navigated TKA
      (4%) compared with conventional TKA (6.5%).

PMID- 24683656
TI  - Comparison of radiographic appearance and bone scintigraphy in fracture
      nonunions.
AB  - Many surgeons assess the biological activity of fracture nonunions by the
      presence or absence of callus on radiographs. However, the assessment of
      biological activity by radiographic appearance alone is controversial. Bone
      scintigraphy reflects blood flow and new bone formation; therefore, it is useful
      in assessing such biological activity in nonunion cases. This retrospective study
      compared radiographs with Tc-99m bone scintigraphy in 48 patients with uninfected
      nonunions. Positive uptake was observed in all cases. The uptake patterns were
      classified into 4 types: type 1, intense, uniform uptake; type 2A, a definite
      photon-deficient cleft between 2 areas of intense uptake; type 2B, a photon
      deficient area other than type 2A; and type 3, an intermediate pattern with
      uneven, distributed uptake. The percentage of type 1 with intense uptake does not
      decrease with time, and type 2 does not increase. When uptake was compared in
      patients with a nonunion and a united fracture, higher uptake in nonunion was
      seen in 46% and lower uptake was seen in 27%. All cases of hypertrophic and more
      than half of oligotrophic nonunions were type 1. Type 2 was seen in 17% of
      oligotrophic, 67% of comminuted, 100% of defect, and 57% of atrophic nonunions.
      Poor callus visualization may not preclude biological activity. Long duration
      from injury may not equate to declines in biological activity. Comparing uptake
      in nonunions and united fractures in the same patient may help to assess
      biological activity. The photon-deficient area is helpful to assess the necessity
      of bone graft or other osteogenic supplementation.

PMID- 24683657
TI  - Efficacy of rhBMP-2 versus iliac crest bone graft for posterior C1-C2 fusion in
      patients older than 60 years.
AB  - Few studies have specifically examined the efficacy of recombinant human bone
      morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) in
      posterolateral lumbar spine fusion. The purpose of this study was to report the
      clinical outcomes in elderly patients treated with posterior C1-C2 fusion with
      iliac crest bone graft (ICBG) plus rhBMP-2/ACS vs ICBG alone. One hundred forty
      patients older than 60 years were enrolled in this prospective, randomized trial
      and underwent instrumented C1- C2 fusion. Patients were divided into 2 groups
      based on fusion material. The ICBG group comprised patients who received ICBG
      alone, and the rhBMP-2/ACS group comprised patients who received ICBG plus rhBMP
      2/ACS. The groups were compared based on operative time, estimated blood loss,
      hospital length of stay, clinical results, perioperative complications, fusion
      rate, fusion time, and revision rate. There were no significant differences in
      operative time, estimated blood loss, length of stay, and intraoperative
      complications between the 2 groups. Improvements in visual analog scale scores
      and Japanese Orthopaedic Association scores over the 2-year follow-up period were
      similar between groups. The fusion rate was 82.4% (56 of 68) in the rhBMP-2/ACS
      group and 78.7% (52 of 66) in the ICBG group (P=.782). Mean fusion time was 11
      days shorter in the rhBMP-2/ACS group (81.8+/-29.4 days) than in the ICBG group
      (92.9+/-23.7 days) (P=.034). There were more wound complications requiring
      treatment in the rhBMP-2/ACS group (n=6; 8.8%) than in the ICBG group (n=2;
      3.0%), although this was not statistically significant (P=.118). The use of rhBMP
      2/ACS for posterior C1-C2 fusion appears to result in a relatively shorter fusion
      time, but there may be an increased risk of posterior cervical wound
      complications.

PMID- 24683658
TI  - Prevention of arthrofibrosis after arthroscopic screw fixation of tibial spine
      fracture in children and adolescents.
AB  - Arthrofibrosis is a major complication of tibial spine fracture treatment in
      children, potentially resulting in knee pain, quadriceps weakness, altered gait,
      decreased function, inability to return to sports, and long-term osteoarthritis.
      Thus, prevention rather than treatment of arthrofibrosis is desirable. The
      purpose of this study was to evaluate an aggressive postoperative rehabilitation
      and early intervention approach to prevent permanent arthrofibrosis after tibial
      spine fracture treatment and to compare epiphyseal and transphyseal screws for
      fixation. A consecutive series of 24 patients younger than age 18 with displaced
      type II and III tibial spine fractures who underwent arthroscopic reduction and
      screw fixation between 2006 and 2011 were retrospectively reviewed. Final range
      of motion was compared between patients with epiphyseal (n=12) and transphyseal
      (n=9) screws. One-third (4 of 12) of patients with epiphyseal screws underwent
      arthroscopic debridement and screw removal approximately 3 months
      postoperatively; 3 patients lacked 5 degrees  to 15 degrees  of extension, 1
      experienced pain with extension, and 1 had radiographic evidence of screw
      pullout, loss of reduction, and resultant malunion. In the transphyseal screw
      group, 3 patients had 10 degrees  loss of extension, and all corrected after
      arthroscopic debridement and screw removal. The two groups did not significantly
      differ in time to hardware removal or return to sports or final range of motion.
      No growth disturbances were identified in patients after transphyseal screw
      removal. An aggressive approach of postoperative rehabilitation and early
      intervention after arthroscopic reduction and screw fixation of tibial spine
      fractures in children was successful in preventing permanent arthrofibrosis.

PMID- 24683659
TI  - Allograft cortical strut for reconstruction of space-occupying bone lesions.
AB  - Space-occupying bone lesions present orthopedic surgeons with clinical and
      operative challenges. Multiple reconstructive procedures have proven successful
      for small bone lesions but lack the structural support necessary for
      reconstruction of larger lesions. This study reports the clinical outcomes of
      patients undergoing excision and reconstruction of large bone lesions with
      allograft cortical struts without additional internal fixation. This
      retrospective outcomes study reviewed patients who underwent surgical curettage
      and cortical strut allograft reconstruction of any space-occupying bone lesion.
      Clinical, surgical, and imaging data were collected. The primary outcome measures
      were lesion healing, graft incorporation, long-term pain, return to activity, and
      presence of complications/recurrences. Seventeen patients met the inclusion
      criteria. At least partial lesion healing and allograft incorporation was
      identified in 15 of 17 lesions. Of the 15 patients who did not sustain a
      recurrence, only 1 did not return to full activities. Mean lesion volume was 107
      cc. Average follow-up was 19.6 months. Two recurrences were identified, and no
      other major complications were identified.

PMID- 24683660
TI  - Laminar reclosure after single open-door laminoplasty using titanium miniplates
      versus suture anchors.
AB  - Laminar closure is associated with expansive open-door laminoplasty. Suture
      anchor fixation and titanium miniplate fixation are used to prevent laminar
      reclosure. However, few studies have compared the clinical effects of the 2
      fixation methods. The authors performed a prospective study of 55 patients with
      cervical spondylotic myelopathy who underwent single open-door laminoplasty with
      suture anchor fixation (n=30) or titanium miniplate fixation (n=25) from June
      2005 to May 2011. Clinical and radiologic outcomes were evaluated at 1 week and 1
      year postoperatively. There were no significant differences between the 2 groups
      in terms of Japanese Orthopaedic Association (JOA) scores, JOA recovery rates at
      1 week postoperatively, and the incidence of C5 palsy. Compared with the suture
      anchor group, the recovery rate in the titanium miniplate group was significantly
      higher at 1 year postoperatively, and the incidence of axial symptoms and mean
      axial symptom scores were significantly lower at 1 week, but not 1 year,
      postoperatively. Radiologic examination showed no significant differences in the
      anteroposterior diameter of the spinal cord and the vertebral body-to-spinal cord
      distance between the 2 groups. At 1 year postoperatively, the opening angle in
      the suture anchor group was significantly less than that in the titanium
      miniplate group. Titanium miniplate fixation is more effective than suture anchor
      fixation in preventing laminar closure, accompanied by a higher JOA recovery rate
      at 1-year follow-up and a lower incidence of axial symptoms.

PMID- 24683661
TI  - Can viscosupplementation be used in the hip? An Italian perspective.
AB  - Viscosupplementation is the intra-articular administration of preparations
      containing hyaluronic acid or hyaluronate intended to restore the normal
      biological properties of hyaluronic acid normally found in synovial fluid.
      Infiltration of hyaluronic acid in the arthritic hip is a more recent technique
      than viscosupplementation of the knee due to the greater technical difficulty of
      infiltration to the hip, which requires fluoroscopic or ultrasound guidance. The
      introduction of high-molecular-weight hyaluronic acid in the treatment permits a
      single administration and has helped diffuse hip infiltration treatment. A single
      infiltration reduces patient discomfort caused by the procedure and allows
      treatment of a larger number of patients. Although the literature has
      unequivocally proven the possibility of reducing pain in patients affected by hip
      arthritis following infiltration, the molecular weight and density, the number of
      infiltrations required for long-term results, and the most appropriate
      indications for infiltration treatment have yet to be clarified. Selecting the
      patient is the first obstacle to be overcome. Therefore, infiltration should be
      considered as an option for patients with initial pain symptoms who have not yet
      been listed for joint prosthesis surgery. The radiographic criteria require at
      least a partly preserved joint space, and the clinical criteria of persistent hip
      pain and full joint mobility seem to be sufficiently effective for selection.

PMID- 24683662
TI  - Small bone islands: unusual clinical symptomatology.
AB  - Bone islands are usually considered benign, stable, nonprogressive lesions,
      radiographically characterized by an ovoid, round, or oblong homogeneously dense
      and sclerotic focus in the spongiosa, with a preference for the long bones and
      the pelvis. Benign solitary bone islands are usually believed to be asymptomatic,
      with no necessity for treatment. Symptomatic bone islands reported in the
      literature are characterized by a diameter greater than 2 cm, belonging to the
      category of giant bone islands. The authors report a rare case starting from a
      painful symptomatology and involving dense sclerotic bone lesions of less than 2
      cm, thus falling into the category of small bone islands. The patient underwent a
      surgical resection to achieve complete recovery. Normally, small bone islands do
      not explain the pain in patients who present with symptomatology when they are
      detected during radiographic studies. Based on this case, the authors believe
      that even small bone islands can be the cause of symptomatology and justify a
      surgical procedure if all medical investigations suggest no other possible causes
      of the pain.

PMID- 24683663
TI  - Isolated Lactobacillus chronic prosthetic knee infection.
AB  - Lactobacillus is a gram-positive rod bacteria found primarily in the
      gastrointestinal and female genital tracts. Prosthetic infections in implants are
      being increasingly reported. The authors present a case of a 58-year-old patient
      with Lactobacillus septic prosthetic knee joint infection. To the authors'
      knowledge, this is the first reported case of chronic prosthetic knee infection
      with isolated Lactobacillus species. Lactobacillus has been most commonly
      implicated with bacteremia and endocarditis and rarely with pneumonia,
      meningitis, and endovascular infection, and a vast majority of the cases are
      reported in immunocompromised patients. In the current case, diabetes mellitus,
      hepatitis, malnutrition, anemia, and liver failure were comorbid conditions,
      placing the patient at increased risk of infection. The findings suggest that
      further case series are necessary to establish the significance of Lactobacillus
      as an etiologic agent in chronic low-virulence, and potentially vancomycin
      resistant, prosthetic joint infection. The need also exists for further research
      aimed at the risk of prosthetic joint infection with oral intake of certain
      probiotic foods and supplements. The goal of this case report is to bring to
      light the potential of this organism to be a cause of subtle chronic prosthetic
      joint infection.

PMID- 24683664
TI  - Chondroblastoma of the patella with aneurysmal bone cyst.
AB  - Chondroblastoma of the patella is rare. Aneurysmal bone cysts, which develop from
      a prior lesion such as a chondroblastoma, are seldom seen in the patella. The
      authors report a case of a 36-year-old man who presented with 2 years of right
      knee pain without calor, erythema, pain on palpation, or abnormal range of
      motion. Radiological studies suggested aneurysmal bone cyst. The lesion was
      excised with curettage and the residual cavity filled with autogenous bone graft.
      Histopathology revealed chondroblastoma associated with a secondary aneurysmal
      bone cyst. In the follow-up period, the patient demonstrated normal joint
      activities with no pain. Normal configuration of the patella and bone union were
      shown on plain radiographs. The authors present a review of the literature of all
      cases of patellar chondroblastoma with aneurysmal bone cyst. This case is the
      14th report of aneurysmal bone cyst arising in a chondroblastoma of the patella.
      According to the literature, computed tomography and magnetic resonance imaging
      are useful in the study of these lesions. The pathologic diagnosis is based on
      the presence of chondroblastoma and aneurysmal bone cyst. Treatment of this
      lesion includes patellectomy, curettage alone, and curettage with bone grafting.
      Despite the risk of recurrence of this lesion in the patella, the authors first
      recommend curettage followed by filling the cavity with bone graft. To protect
      the anterior tension of the patella intraoperatively, the bone window should be
      made at the medial edge of the patella to perform the curettage and bone
      grafting.

PMID- 24683666
TI  - [Looking back at medical postgraduate certification - in medias res!].

PMID- 24683665
TI  - Avulsive axillary artery injury in reverse total shoulder arthroplasty.
AB  - In addition to neurologic injuries such as peripheral nerve palsy, axillary
      vessel injury should be recognized as a possible complication of reverse total
      shoulder arthroplasty. Limb lengthening associated with Grammont-type reverse
      total shoulder arthroplasty places tension across the brachial plexus and
      axillary vessels and may contribute to observed injuries. The Grammont-type
      reverse total shoulder arthroplasty prosthesis reverses the shoulder ball and
      socket, shifts the shoulder center of rotation distal and medial, and lengthens
      the arm. This alteration of native anatomy converts shearing to compressive
      glenohumeral joint forces while augmenting and tensioning the deltoid lever arm.
      Joint stability is enhanced; shoulder elevation is enabled in the rotator cuff
      deficient shoulder. Arm lengthening associated with reverse total shoulder
      arthroplasty places a longitudinal strain on the brachial plexus and axillary
      vessels. Peripheral nerve palsies and other neurologic complications of reverse
      total shoulder arthroplasty have been documented. The authors describe a patient
      with rotator cuff tear arthropathy and a history of radioulnar synostosis who
      underwent reverse total shoulder arthroplasty complicated by intraoperative
      injury to the axillary artery and postoperative radial, ulnar, and
      musculocutaneous nerve palsies. Following a seemingly unremarkable placement of
      reverse shoulder components, brisk arterial bleeding was encountered while
      approximating the incised subscapularis tendon in preparation for wound closure.
      Further exploration revealed an avulsive-type injury of the axillary artery.
      After an unsuccessful attempt at primary repair, a synthetic arterial bypass
      graft was placed. Reperfusion of the right upper extremity was achieved and has
      been maintained to date. Postoperative clinical examination and electromyographic
      studies confirmed ongoing radial, ulnar, and musculocutaneous neuropathies.

PMID- 24683667
TI  - Multiple imputation of missing phenotype data for QTL mapping.
AB  - Missing phenotype data can be a major hurdle to mapping quantitative trait loci
      (QTL).Though in many cases experiments may be designed to minimize the occurrence
      of missing data,it is often unavoidable in practice; thus, statistical methods to
      account for missing data are needed.In this paper we describe an approach for
      conjoining multiple imputation and QTL mapping.Methods are applied to map genes
      associated with increased breathing effort in mice after lung inflammation due to
      allergen challenge in developing lines of the Collaborative Cross, a new mouse
      genetics resource. Missing data poses a particular challenge in this study
      because the desired phenotype summary to be mapped is a function of incompletely
      observed dose-response curves. Comparison of the multiple imputation approach to
      two naive approaches for handling missing data suggest that these simpler methods
      may yield poor results: ignoring missing data through a complete case analysis
      may lead to incorrect conclusions, while using a last observation carried forward
      procedure, which does not account for uncertainty in the imputed values, may lead
      to anti-conservative inference. The proposed approach is widely applicable to
      other studies with missing phenotype data.

PMID- 24683668
TI  - [Autoinflammation - patological impact of dysregulation of inflammatory
      reaction].

PMID- 24683669
TI  - [Vitamin D relation to the head and neck cancer].

PMID- 24683670
TI  - [Therapy of severe sepsis in year 2013].

PMID- 24683671
TI  - The human and economic cost of hidden hunger.
AB  - BACKGROUND: Micronutrient malnutrition is a public health problem in many
      developing countries. Its negative impact on income growth is recognized in
      principle, but there are widely varying estimates of the related economic cost.
      OBJECTIVE: To discuss available studies that quantify the cost of micronutrient
      malnutrition, and to develop an alternative framework and apply it to India.
      METHODS: Detailed burden of disease calculations are used to estimate the
      economic cost of micronutrient malnutrition based on disability-adjusted life
      years (DALYs) lost. RESULTS: The short-term economic cost of micronutrient
      malnutrition in India amounts to 0.8% to 2.5% of the gross domestic product.
      CONCLUSIONS: Although the results confirm that micronutrient malnutrition is a
      huge economic problem, the estimates are lower than those of most previous
      studies. The differences may be due to differences in underlying assumptions,
      quality of data, and precision of calculation, but also to dynamic interactions
      between nutrition, health, and economic productivity, which are difficult to
      capture. Clear explanation of all calculation details would be desirable for
      future studies in order to increase credibility and transparency.

PMID- 24683672
TI  - Food-poverty status and food insecurity in rural West Lombok based on mothers'
      food expenditure equivalency.
AB  - BACKGROUND: When the Central Bureau for Statistics (CBS) developed a national
      food-poverty line for Indonesia, some aspects, such as food availability,food
      beliefs, and food habits, were not considered. In addition, the reference
      population was determined on the basis of their nonfood expenditures. OBJECTIVE:
      To develop and use a method applicable in any given sociocultural setting, as
      well as to determine food-poverty status in rural West Lombok, Indonesia, using
      mothers'food expenditure equivalency (FEE). METHOD: Mothers' actual food intake
      determined by a modified 24-hour recall served to establish FEE. The results were
      verified with household food-security measures based on the US Household Food
      Security/Hunger Measurement (US HFSSM), and the mothers' nutritional status was
      assessed by the body-mass index (BMI). RESULTS: Most mothers (72%) were food-poor
      and 79% were also food-insecure. Food poverty has a positive correlation with
      household food insecurity. The severely food poor also had the highest risk of
      household food insecurity. The nutritional status of mothers showed no
      correlation with food-poverty status and therefore was not found to be an
      appropriate indicator of food poverty in this cultural setting. CONCLUSIONS:
      Because most food consumed by mothers was purchased, financial security plays a
      key role in determining family food sufficiency, in terms of both quantity and
      variety. Mothers' BMI status differed between the food-poor and non-food-poor
      groups, but the difference was not statistically significant, suggesting that in
      our setting the food-poverty line cannot be used to identify physiological need
      but is rather more of a social and economic indicator. We suggest the use of US
      HFSSM questionnaires as a simple alternative means to assess both food-poverty
      and food-security status, mainly because the method is simple to apply and
      corroborates our findings using area-specific FEEs. Finally, our study results
      suggest a number of follow-up investigations.

PMID- 24683673
TI  - Does provision of food in school increase girls' enrollment? Evidence from
      schools in sub-Saharan Africa.
AB  - BACKGROUND: The problem of low female literacy rates in Africa starts with low
      primary school enrollment, particularly in areas of high food insecurity. The
      provision of food in, and through, schools is considered to be one way of
      enrolling more girls in school, keeping them enrolled, and enhancing their adult
      well-being and productivity as a result. OBJECTIVE: To investigate the effects of
      provision of food and additional take-home rations in schools on girls'
      enrollment. METHODS: A retrospective cross-sectional study was designed based on
      school-level surveys in 32 African countries between 2002 and 2005. The study
      population consisted of girls and boys in primary schools targeted by the World
      Food Programme (WFP) and located in food-insecure areas that also suffered from
      lack of access to education. RESULTS: Provision of food in schools through the
      Food for Education (FFE) program contributed to increasing absolute enrollment in
      WFP-assisted schools by 28% for girls and 22% for boys in the first year. Post
      year-one enrollment patterns varied according to the type of FFE program. Where
      provision of take-home rations for girls was combined with on-site feeding for
      all pupils, the increase in girls' absolute enrollment was sustained at 30% after
      the first year. However, in schools providing on-site feeding alone, the rate of
      increase in absolute enrollment after the first year reverted to the rates of
      increase found in the year prior to FFE implementation. The provision of take
      home rations also appeared to reduce the dropout rate of female students,
      particularly in the higher grades. CONCLUSIONS: FFE programs can have a lasting
      positive influence on school enrollment and, by providing extra take-home rations
      to girls, in addition to on-site feeding, can make a strong contribution to the
      Millennium Development Goals.

PMID- 24683674
TI  - Effect of daily versus once-weekly home fortification with micronutrient
      Sprinkles on hemoglobin and iron status among young children in rural Bangladesh.
AB  - BACKGROUND: The effectiveness of commonly suggested public health interventions
      to control childhood iron-deficiency anemia has been low. OBJECTIVE: To determine
      whether iron provided in Sprinkles daily or in a higher dose once weekly affected
      hemoglobin, serum ferritin levels, and serum transferrin receptor levels, and to
      determine whether there were differences in the effects of the two regimens.
      METHODS: In this cluster-randomized, community-based trial conducted in rural
      areas of Bangladesh, 136 children aged 12 to 24 months with mild to moderate
      anemia (hemoglobin 70-109 g/L) were randomly allocated to receive Sprinkles daily
      (12.5 mg of elemental iron, n = 79) or once weekly (30 mg of elemental iron, n =
      73) for 8 weeks. Hemoglobin, serum ferritin, and serum transferrin receptor were
      assessed at the start and end of the intervention. RESULTS: In both groups, there
      were significant increases in hemoglobin and serum ferritin and a significant
      decrease in serum transferrin receptor (p < .01). There were no significant
      differences between the groups in the increases in hemoglobin (16.1 +/- 13.2 g/L
      for the group receiving Sprinkles daily and 12.3 +/- 13.3 g/L for the group
      receiving Sprinkles once weekly) and serum ferritin (10.6 and 5.7 microg/L,
      respectively). The decrease in serum transferrin receptor also did not
      significantly differ between the groups (median, -2.5 and -1.8 mg/L,
      respectively). The prevalence rates of iron-deficiency anemia, depleted iron
      stores, and tissue iron deficiency decreased significantly within each group (p <
      .01), with no significant differences between the groups. CONCLUSIONS: Home
      fortification of complementary foods with Sprinkles given either daily or once
      weekly improved iron-deficiency anemia and iron status among young children.

PMID- 24683675
TI  - Effects of various iron fortificants on sensory acceptability and shelf-life
      stability of instant noodles.
AB  - BACKGROUND: Iron-deficiency anemia is the most common nutritional problem in
      Thailand and many developing countries. One of the most sustainable and cost
      effective strategies for combating iron deficiency is fortification of staple
      foods with iron. OBJECTIVE: In this study, the feasibility of fortifying instant
      noodles with different forms of iron fortificants (ferrous sulfate [FS], ferric
      sodium ethylenediaminetetraacetic acid [NaFeEDTA], and encapsulated H-reduced
      elemental iron [EEI] was evaluated, and the fortified noodles were compared with
      unfortified noodles for changes in physical, chemical, and sensory qualities.
      METHODS: Wheat flour used to make instant noodles was fortified to produce a
      concentration of 5 mg of iron per 50-g serving of instant noodles (one-third of
      the Thai recommended dietary intake). RESULTS: Analytical data showed that the
      iron contents were close to 5 mg per serving of noodles fortified with FS,
      NaFeEDTA, or EEI (5.27 +/- 0.10, 4.27 +/- 0.07, and 5.26 +/- 0.47 mg,
      respectively). The color quality (measured by L*, lightness, and b* yellowness)
      of the raw dough sheet and of uncooked and cooked instant noodles fortified with
      FS was lower than that of the unfortified, but color quality was not changed by
      the addition of NaFeEDTA. The overall sensory acceptability scores of unfortified
      and fortified noodles were about 6 ("like slightly"). No metallic odor was
      observed. During 3 months of storage at room temperature, the iron fortificants
      did not affect the peroxide level, color, or sensory qualities of the product.
      CONCLUSIONS: Iron fortification of wheat flour used to make instant noodles is
      feasible. NaFeEDTA is the preferred fortificant because of its nonsignificant
      effect on the color and sensory quality of the products.

PMID- 24683676
TI  - Fortification of drinking water to control iron-deficiency anemia in preschool
      children.
AB  - BACKGROUND: Iron-deficiency anemia is the most common type of micronutrient
      malnutrition in the world. Its etiology and control are well understood, but the
      problem persists and is increasing in some developing countries. Iron
      fortification of mass-consumption foods is considered one of the most viable
      approaches to deliver bioavailable iron to the population. OBJECTIVE: To review
      and analyze the use of drinking water as an iron vehicle to reduce ferropenic
      anemia in developing countries. METHODS: Drinking water with added iron compounds
      was offered to preschool children at day-care centers in Brazil. Iron solutions
      were prepared with 10 mg to 20 mg iron/L. Clinical and anthropometric
      measurements and blood hemoglobin concentrations were obtained at the beginning
      of each study and 4 to 8 months later. RESULTS: No problems with acceptability or
      side effects were observed. Daily water intake by children was around 500 mL.
      Iron-deficiency anemia was found in all studies. Control children not receiving
      iron supplementation mantained their initial hemoglobin level. Anemia was reduced
      in the groups receiving iron-fortified drinking water. CONCLUSIONS: Based on
      physical properties, tests in rats, and studies on preschool children at
      Brazilian day-care centers, we have shown that drinking water locally fortified
      with iron compounds should be considered and used as a worldwide available
      vehicle to control iron-deficiency anemia. Drinking water, besides being
      universally available, is a locally available vehicle, easily fortified, can be a
      vehicle for hydrosoluble iron, and reduces iron-deficiency anemia in preschool
      children.

PMID- 24683677
TI  - Feasibility and use of vitamin A-fortified vegetable oils among consumers of
      different socioeconomic status in Thailand.
AB  - BACKGROUND: Vitamin A losses infortified vegetable oils can differ, depending
      upon the cooking and distribution conditions of a country. OBJECTIVE: To
      determine vitamin A losses in different vegetable oils during transportation,
      cooking, and storage among consumets of different socioeconomic status. METHODS:
      Soybean, rice bran, and palm oils were fortified with vitamin A palmitate at 267
      microg/15 mL. The oils were packaged in 5-L metal cans and 250-mL polyethylene
      terephthalate (PET) bottles and then stored under light and dark conditions.
      Unopened and opened bottles were stored for 13 and 4 weeks, respectively.
      Fortified palm oil also was bulk transported in trucks and packaged in 1-kg
      polypropylene bags that were closed with rubber bands. Vitamin losses were
      measured after cooking at 120 degrees and 170 degrees C for 5 and 10 minutes in
      iron, aluminum, Teflon, and glass pans. RESULTS: Vitamin A losses of oils in PET
      bottles stored under light conditions were 20% to 25% at the 5th week and became
      greater than 80% after 13 weeks, whereas losses under dark conditions and in
      metal containers were less than 15%. Loss during bulk transportation was 25%,
      with no change in peroxide value. Losses in opened bottles after 4 weeks under
      light conditions were 50% to 90% based on the degree of oil unsaturation;
      however, losses under dark conditions were less than 5%. Losses after cooking at
      120 degrees and 170 degrees C for 10 minutes were less than 5% and 15%,
      respectively. The type of pan did not affect the amount of loss. The peroxide
      values of oils in bottles increased during storage under light conditions.
      CONCLUSIONS: Fortification of vegetable oils with vitamin A for consumers of
      different socioeconomic status is feasible; however, light protection is needed
      for better stability.

PMID- 24683678
TI  - Home fortification in emergency response and transition programming: experiences
      in Aceh and Nias, Indonesia.
AB  - BACKGROUND: Improving the nutritional status of an emergency-affected population
      is essential, because undernutrition increases infection risk and is linked to
      more than 50% of childhood deaths in developing countries. Emergency food aid
      addresses nutritional needs, including micronutrient deficiencies, but is
      provided only for a limited time and uses few items, so the needs of specific
      target groups are often not fully met. OBJECTIVE: To describe the post-tsunami
      experience with distribution of Vitalita Sprinkles in Aceh and Nias and to
      analyze the monitoring data gathered for the emergency response. METHODS:
      International agencies such as Helen Keller International and partners provided
      micronutrients in response to the tsunami emergency in Aceh and Nias and to
      analyze the monitoring data gathered for the emergency response. RESULTS: In
      March and April 2006, the percentage of children aged 6 months to 59 months who
      had consumed Vitalita in the previous month was more than 70% in 5 of 11
      districts evaluated, 40% to 70% in another five districts, and 32% in one
      district. An independent survey found 25% less anemia among recipients. Almost
      all mothers interviewed during March to April 2006 (96.3%) had heard about
      Vitalita and recognized its packaging, 69% said that Vitalita contained vitamins
      for under-fives, 86% knew the appropriate target group for Vitalita, and 83% said
      it had to be mixed with solid food. Of the 26% that reported not having given
      Vitalita to their child in the last month, 90.5% said that their child did not
      like it. CONCLUSIONS AND LESSONS LEARNED: Because the product, including its
      concept, was new, appropriate information and training was required as well as a
      thorough introduction to the beneficiaries, particularly on proper use, to ensure
      acceptance. This experience demonstrates that providing micronutrients as part of
      emergency relief and transition programming, as recently recommended by the World
      Health Organization/UNICEF/World Food Program, is feasible.

PMID- 24683679
TI  - Dialyzability of minerals in corn masa gruel (atole) fortified with different
      iron compounds: effects of ascorbic acid, disodium EDTA, and phytic acid.
AB  - BACKGROUND: Lime-treated corn gruel (atole) is a common weaning food in iron
      deficient populations, especially in Mexico and Central America, and is a
      potential vehicle for fortification with iron. OBJECTIVE: The objective of this
      study was to screen promising iron compounds for use in the fortification of
      atole, using in vitro enzymatic digestion-dialysis techniques, while also
      considering their response to known iron absorption enhancers and inhibitors.
      METHODS: Atole, unaltered or preincubated with phytase, was fortified with iron
      (10 mg/L) from ferrous sulfate, ferrous bisglycinate, or ferrous fumarate, or
      with ferric chloride, ferric ammonium citrate, or ferric sodium
      ethylenediaminetetraacetic acid (NaFeEDTA), and submitted to in vitro digestion.
      Dialysis of calcium, copper, iron, phosphorus, and zinc (analyzed by inductively
      coupled plasma atomic emission spectrometry) was measured when atole was
      fortified with iron compounds alone or together with ascorbic acid or disodium
      ethylenediaminetetraacetic acid (Na2EDTA). RESULTS: Iron dialyzability was higher
      with NaFeEDTA (p < .05) than with all other iron compounds, which did not differ
      among themselves in iron dialyzability. Addition of ascorbic acid had no
      significant effect on iron dialysis, whereas Na2EDTA enhanced iron dialyzability
      by 7 to 10 times in unaltered atole and 15 to 20 times in phytase-preincubated
      atole (p < .05). Addition of Na2EDTA always increased intrinsic zinc
      dialyzability, and most of the time this increase was significant. Phytase
      pretreatment generally increased mineral dialysis. CONCLUSIONS: Adding EDTA
      (either as NaFeEDTA or as Na2EDTA) to atole can increase the dialyzability of
      ferrous and ferric iron compounds and enhance the dialyzability of intrinsic zinc
      without any negative effects on calcium, phosphorus, or copper dialysis.

PMID- 24683680
TI  - Variation in the diets of Filipino women over 9 months of continuous observation.
AB  - BACKGROUND: The variability in habitual intakes of most components in the
      Philippine diet is unknown. OBJECTIVE: To perform a quantitative evaluation of
      the traditional Philippine diet using data collected over an extended period of
      time. We sought to identify seasonal variations and within-subject components of
      variation in nutrient intake. METHODS: A quantitative evaluation of the
      Philippine diet was conducted in convents in metropolitan Manila as part of an
      efficacy trial to examine biofortified rice as an approach to improve iron
      nutritional status. Weighed food intakes were conducted on 54 days in each of
      more than 300 religious sisters over 9 months in 10 convents. The sisters
      consumed their habitual diets except for the substitution of one variety of rice
      for another. RESULTS: More than 40% of calories were derived from rice, with
      protein from meat and fish comprising 18% of calories. There were significant
      variations in macronutrient and micronutrient intakes across seasons of the year,
      with more rice consumed in the wet season and more fruits, eggs, milk, and
      beverages consumed in the dry season. The day-to-day within-subject variation
      (CV) in median intake was 23% for energy, 31% for protein, 42% for iron, and 138%
      for vitamin A. CONCLUSIONS: These novel data show that traditional Filipino
      dietary patterns have substantial individual variation and are inadequate in
      certain micronutrients. This quantitative evaluation of diet can provide a
      reference point for dietary adequacy.

PMID- 24683681
TI  - Constraints on the delivery of animal-source foods to infants and young children:
      case studies from five countries.
AB  - BACKGROUND. Optimal feeding of infants and young children in developing countries
      includes daily feeding of animal-source foods. OBJECTIVE. To evaluate constraints
      on the availability of animal-source foods at the community level, access to
      animal-source foods at the household level, and intake of animal-source foods at
      the individual level among children under 3 years of age in case studies in five
      developing countries: Mexico, Peru, Haiti, Senegal, and Ethiopia. METHODS: Data
      were obtained from published and unpublished research and from program
      experiences of health and agriculture specialists. RESULTS: In Ethiopia, 27% to
      51% of case-study children had consumed an animal-source food on the previous
      day; from 56% to 87% of children in the other case-study sites had consumed an
      animal-source food on the previous day. Data on intake of animal-source foods in
      grams were only available for the Latin American case-study sites, where daily
      milk intake was high in Mexico and Peru (195 and 180 g/day, respectively) and the
      intakes of meat, fish, and poultry (MFP) (29.0 and 13.6 g/day) and of egg (18.4
      and 4.9 g/day) were low. The conceptual model guiding this work identified more
      constraining factors at the community and household levels than at the individual
      level. The most common constraints on feeding animal-source foods to young
      children were poverty, animal health, and land degradation at the community
      level; cost of animal-source foods and limited livestock holdings at the
      household level; and caregivers' perceptions of giving animal-source foods to
      children at the individual level. CONCLUSIONS: For program planning, it is useful
      to simultaneously consider factors that affect community availability of
      household access to, and children's intake of animal-source foods. Efforts to
      overcome individual-level constraints on intake of animal-source foods should be
      coupled with activities to address community and household constraints.

PMID- 24683682
TI  - Zinc status of Iranian preschool children.
AB  - BACKGROUND: Zinc deficiency is one of the most prevalent micronutrient
      deficiencies in developing countries, including Iran. The main direct causes of
      zinc deficiency are insufficient zinc intake, absorption or metabolic disorder,
      and increase in need during acute growth periods. OBJECTIVE: To determine the
      prevalence of zinc deficiency in preschool boys and girls in urban and rural
      populations in order to assist policy makers. Children of preschool age (i.e., 6
      years old in Iran) were studied because interventions in this age group are
      believed to result in greater improvement in learning skills once these children
      enter school. METHODS: A national cross-sectional study was carried out on 4,374
      randomly selected healthy preschool children from Iranian families in 2001. Serum
      zinc concentration was measured by atomic absorption spectrometry. The cutoff
      point for zinc deficiency was set at a serum level of 10 micromol/L (65
      microg/dL). RESULTS: The prevalence of zinc deficiency was estimated at
      approximately 19.3%. The highest prevalence was seen in the region that includes
      Sistan and Baluchistan, South Khorasan, and the southeast area of Kerman and the
      lowest in the region of Boushehr, Hormozgan, and South Khoozestan. The prevalence
      of zinc deficiency was significantly higher in rural areas than in urban areas.
      No significant difference in prevalence was seen between boys and girls.
      CONCLUSIONS: In the long run, nutritional security and increased access to and
      intake of foods with high levels of zinc are the most sustainable strategies to
      overcome zinc deficiency. Fortification of staple foods, improved quality of
      traditional bread, and supplementation for at-risk population groups are
      considered short- and mid-term interventions. Nutrition education and behavioral
      change may be long-term strategies.

PMID- 24683683
TI  - Mediterranean diet, traditional foods, and health: evidence from the Greek EPIC
      cohort.
AB  - BACKGROUND: For more than 50 years, the traditional Mediterranean diet has been
      considered health-promoting, but it was not until the mid-1990s that the topic
      began to receive increased scrutiny and prominence. OBJECTIVE: To highlight the
      health benefits of the Mediterranean diet as documented by studies undertaken
      mostly within a large countrywide general population cohort in Greece. METHODS:
      The Greek EPIC (European Prospective Investigation into Cancer) cohort, a
      prospective study based on volunteers from the general population of Greece, and
      other investigations with converging objectives. In the Greek EPIC cohort of more
      than 28,000 volunteers being followed for more than 10 years, several findings on
      the association of diet with chronic diseases have been published in the
      international scientific literature. RESULTS: The traditional Mediterranean diet
      of Greece is associated with reduced total mortality as well as reduced mortality
      from coronary heart disease and cancer. It is applicable in other Western
      populations, where it has also been shown to be inversely related to total
      mortality. Moreover, the traditional Mediterranean diet may be optimal for
      patients who have suffered a coronary infarct, and it does not promote obesity.
      Traditional foods are integral components of the Mediterranean diet and may
      contribute to its health-promoting attributes. CONCLUSIONS: The traditional
      Mediterranean diet may be an optimal diet both for healthy people and for
      patients with coronary heart disease and other chronic conditions.

PMID- 24683684
TI  - Lessons learned in controlling the burden of malnutrition.

PMID- 24683685
TI  - Nutrition in public health: an unfinished story.

PMID- 24683686
TI  - Social sciences and malnutrition.

PMID- 24683687
TI  - "Acknowledge nurses' all-weather heroism".

PMID- 24683688
TI  - Nurses' "inspiring" response to floods.

PMID- 24683689
TI  - "Focus on supporting staff when looking at how to improve care".

PMID- 24683690
TI  - "Burnout is not a moral failure so needs empathy, not blame".

PMID- 24683691
TI  - "How a university's attitudes destroy professional practice".

PMID- 24683692
TI  - Using simulation to develop handover skills.
AB  - This article outlines the potential impact of ineffective handover skills on
      nurses' confidence, competence and coordination, as well as on patient safety. It
      focuses on how student nurses can develop their communication skills by looking
      specifically at how the University of Derby used simulation to teach pre
      registration student nurses effective handover techniques.

PMID- 24683693
TI  - Functions and diseases of red and white blood cells.
AB  - Red and white blood cells have two main functions: the carriage of oxygen; and
      defence against microbial attack. The full blood count is one of the most
      frequently requested routine blood tests; it provides key indices such as
      haemoglobin and the number of white cell subsets, and provides information to aid
      diagnosis of a range of conditions, including anaemia, infection, leukaemia,
      myeloma and lymphoma.

PMID- 24683694
TI  - Management of chronic hepatitis B virus.
AB  - The management of chronic hepatitis B is complex due to its four disease stages.
      Monitoring is often required to inform future management; not all patients will
      require interventions. The long-term goals of treatment are to halt disease
      progression and to prevent cirrhosis, hepatocellular carcinoma and liver failure.
      A number of guidelines are available, including those issued by the European
      Association for the Study of Liver Disease and recently published National
      Institute of Health and Care Excellence guidelines. This article, the second in a
      two-part series, discusses the assessment and management of chronic hepatitis B
      in light of recent guidelines and the role of nurses in caring for patients with
      CHB. Part 1 looked at the prevalence and pathophysiology of chronic hepatitis B,
      recommendations for screening high-risk groups and immunisation.

PMID- 24683695
TI  - 60 seconds with Sue Hartley.

PMID- 24683696
TI  - Courage for an open culture.

PMID- 24683697
TI  - Boost your career with a scholarship.

PMID- 24683698
TI  - AHNAs financial strategy as a socially responsible investor.

PMID- 24683699
TI  - At last: moving into person-centered care.

PMID- 24683700
TI  - Holistic assessment person-centered care.

PMID- 24683701
TI  - A closer look at self-determination theory & autonomy in nurse coaching.

PMID- 24683702
TI  - Fitting into your genes and finding the perfect match.

PMID- 24683703
TI  - Person-centered care: enhancing patient (person) engagement.

PMID- 24683704
TI  - Yoga from the pelvic floor.

PMID- 24683705
TI  - From tobacco to tanning beds--it's about children and cancer.

PMID- 24683706
TI  - Keep the lights on for me.

PMID- 24683707
TI  - Introduction: the Affordable Care Act and healthcare delivery in Maryland.

PMID- 24683708
TI  - Maryland physicians lead new quality improvement initiative: innovative pilot
      program tackles hypertension control in the ambulatory setting.

PMID- 24683709
TI  - Community tailored partnerships that work: implementing new models of primary
      care in the state of Maryland.

PMID- 24683710
TI  - Transforming communities to support health: highlights from Maryland's Community
      Transformation Grant.

PMID- 24683712
TI  - Today's physician: knowledge worker or system professional?

PMID- 24683711
TI  - Bug bites: a Maryland menu.

PMID- 24683713
TI  - Expanding options for pancreatic cancer... so where do we go from here?

PMID- 24683714
TI  - Gleason 6 prostate cancer: serious malignancy or toothless lion?
AB  - Autopsy studies of men without known prostate cancer suggest that a substantial
      reservoir of prostate cancer that does not cause symptoms or death exists within
      the population. The majority of these cancers are Gleason 6 tumors and are
      frequently detected by prostate-specific antigen-based prostate cancer
      screening.There is strong evidence from longitudinal cohort studies of men with
      both treated and untreated Gleason 6 prostate cancer to suggest that Gleason 6
      disease, when not associated with higher-grade cancer, virtually never
      demonstrates the ability to metastasize and thus represents an indolent entity
      that does not require treatment. Whether Gleason 6 has a propensity to progress
      to higher-grade cancer is still under investigation. Because the term "cancer"
      has historically been used to represent a disease state that leads to progressive
      illness that is uniformly fatal without treatment, we believe Gleason 6 disease
      should not be labeled with this term. Our challenge now is to develop the
      technology to differentiate true Gleason 6 disease from the higher grades of
      dysplasia with which it can be associated.

PMID- 24683715
TI  - Gleason 6 cancer is still cancer.

PMID- 24683716
TI  - Treating prostate cancer: where do we draw the line?

PMID- 24683717
TI  - How can oncology healthcare professionals make a difference in tobacco control?

PMID- 24683718
TI  - The heavy chain diseases: clinical and pathologic features.
AB  - Heavy chain diseases are a family of rare, systemic syndromes typically
      associated with or representing a variant of a B-cell neoplasm. Their
      characteristic feature is production of a mutated immunoglobulin heavy chain
      incapable of either partnering with light chains in the formation of a full
      immunoglobulin molecule or of being degraded by the proteasome. The abnormal
      heavy chain is detected in urine and/or serum without an associated light chain,
      a pathognomonic finding. Depending on the subtype of the altered heavy chain,
      these conditions can be subclassified as alpha, gamma, or mu heavy chain disease.
      We discuss the clinical presentation; epidemiology; laboratory, radiologic, and
      pathologic features; and treatment options for each of the heavy chain diseases,
      emphasising the importance of an accurate pathologic diagnosis and correct
      interpretation of immunologic studies in their identification.

PMID- 24683719
TI  - Heavy chain diseases: a manifestation of rogue B cells.

PMID- 24683720
TI  - Management of heavy chain diseases: the challenges of biologic heterogeneity.

PMID- 24683721
TI  - Treatment of metastatic pancreatic adenocarcinoma: a review.
AB  - Gemcitabine monotherapy has been the standard of care for patients with
      metastatic pancreatic cancer for several decades. Despite recent advances in
      various chemotherapeutic regimens and in the development of targeted therapies,
      metastatic pancreatic cancer remains highly resistant to chemotherapy. Previous
      studies of several combination regimens showed minimal or no significant change
      in overall survival compared with gemcitabine alone. Secreted protein acidic and
      rich in cysteine (SPARC) overexpression in pancreatic stromal fibroblasts is
      considered one of the major causes of chemotherapy resistance. The nanoparticle
      albumin-bound formulation of paclitaxel (nab-paclitaxel) has been found to be
      superior to other formulations of paclitaxel because of its favorable
      pharmacokinetic properties. Initial preclinical studies showed its synergistic
      effect with gemcitabine in pancreatic cancer, in which nab-paclitaxel is
      sequestered by SPARC to cause stromal depletion and increasing microvasculature,
      resulting in higher gemcitabine concentration within the tumor. In the recent
      phase III multinational Metastatic Pancreatic Adenocarcinoma Clinical Trial
      (MPACT), the combination of gemcitabine and nab-paclitaxel was shown to be
      superior to gemcitabine monotherapy, with an increase in median survival of 1.8
      months. Combination therapy with gemcitabine plus erlotinib, or with gemcitabine
      plus nab-paclitaxel, or the multidrug regimen of leucovorin, fluorouracil,
      irinotecan, and oxaliplatin (FOLFIRINOX) can be considered as first-line
      chemotherapy for patients with metastatic pancreatic cancer. In this review we
      will discuss details of the recently approved combination of gemcitabine and nab
      paclitaxel for first-line treatment of metastatic pancreatic adenocarcinoma and
      compare it with other therapeutic options.

PMID- 24683722
TI  - Treatment of metastatic pancreatic adenocarcinoma: new options and promising
      strategies.

PMID- 24683723
TI  - The war on pancreatic cancer: we are not there yet.

PMID- 24683724
TI  - Active surveillance for African-American men with prostate cancer: of course!
      Pro.

PMID- 24683725
TI  - Active surveillance for African-American men with prostate cancer: proceed with
      caution. Con.

PMID- 24683727
TI  - I was a stranger and you welcomed me. Immigrants deserve justice, care.

PMID- 24683728
TI  - Advocacy: bishops press for immigration reform.

PMID- 24683726
TI  - The management of nongastric MALT lymphomas.

PMID- 24683729
TI  - U.S Catholic institutions: are they living up to their history and promise as
      immigrant integration agencies?

PMID- 24683730
TI  - Supporting the newest among our dear neighbors: how one health system helps
      immigrants to thrive. ghbors.

PMID- 24683731
TI  - Empowering refugees in resettlement.

PMID- 24683732
TI  - Bon Secours language services program: employee translators add to quality care.

PMID- 24683733
TI  - Mercy Health Promoter Model: meeting needs of specific immigrant communities.

PMID- 24683734
TI  - Gardening nutrition programs bloom.

PMID- 24683735
TI  - Doctors from abroad: a cure for the physician shortage in America.

PMID- 24683736
TI  - Medical care for people in transition: symptoms may point to stories.

PMID- 24683737
TI  - Marie Rohde interview with James L. Griffith, MD: global mental health, one
      refugee at a time.

PMID- 24683738
TI  - Human trafficking: why Catholic health care commits to the fight.

PMID- 24683739
TI  - Call it what it is: slavery.

PMID- 24683740
TI  - Human trafficking: look around--it's in our own backyard.

PMID- 24683741
TI  - Our mission: putting a face on immigration.

PMID- 24683742
TI  - Immigration rules create a game too hard to play.

PMID- 24683743
TI  - PSE: an approach that addresses multiple needs.

PMID- 24683744
TI  - What is postulation?

PMID- 24683745
TI  - "Patient stories tell us just what great care is".

PMID- 24683746
TI  - Senior staff face most job losses.

PMID- 24683747
TI  - "Staff opinions are important in creating the NHS we want".

PMID- 24683748
TI  - "Vaccine cost system lets harm from meningitis B continue".

PMID- 24683749
TI  - Meningococcal disease in children and teenagers.
AB  - Meningococcal disease is a leading cause of death in children and young people.
      It causes two major disease processes, meningococcal septicaemia and
      meningococcal meningitis, and often results in long-term health complications. It
      remains a difficult disease to recognise and treat. This article, part one in a
      two-part series, discusses the epidemiology of meningococcal disease and explains
      its pathophysiology as well as signs and symptoms. Part 2, to be published on 19
      March, will review diagnosis, management and prevention.

PMID- 24683750
TI  - Patient identification in blood sampling.
AB  - The majority of adverse reports relating to blood transfusions result from human
      error, including misidentification of patients and incorrect labelling of
      samples. This article outlines best practice in blood sampling for transfusion
      (but is recommended for all pathology samples) and the role of patient
      empowerment in improving safety.

PMID- 24683751
TI  - Impetigo: treatment and management.
AB  - Impetigo is the third most common skin disease in children. It is highly
      infectious and can be transmitted through direct and indirect contact. This
      article discusses the types of impetigo, its cause, diagnosis and management, and
      highlights additional guidance and resources that can support practice.

PMID- 24683752
TI  - 60 seconds with Ann Casey.

PMID- 24683753
TI  - The future of cancer care.

PMID- 24683754
TI  - Assessment of post-operative pain and its management among patients undergoing
      craniotomy.
AB  - Pain assessment and its management in patients undergoing craniotomy, especially
      those with communication barriers, continue to present challenges to nurses. The
      present study was undertaken to assess the level of post-operative pain suffered
      by patients after craniotomy, to identify the activities that increase/relieve
      pain and to find out association between pain score of patients and selected
      variables. A self-prepared validated questionnaire and Wong Bakers Faces pain
      scale were used as the tools. The post-operative pain was mild to moderate and
      decreased from first to third postoperative day. Pain relief was adequate with
      the combination therapy of non-narcotic analgesics and non-steroidal anti
      inflammatory drugs. The study revealed that there was no significant difference
      between the pain perception and age or gender of the patient. The activities that
      increased pain were surgical dressing removal and position changing. Nursing
      staff should focus on assessing and managing post-operative pain to improve
      quality of nursing care in order to improve the comfort of craniotomy patients.

PMID- 24683755
TI  - Long term care.

PMID- 24683756
TI  - Obesity among adolescents of urban and rural schools in Mangalore.
AB  - With a view to identify the occurrence of obesity and its related factors among
      adolescents of selected urban and rural schools. 1200 adolescents from selected
      high schools in Mangalore were recruited through multistage random sampling. A
      demographic Performa and a 5 point rating scale were used to assess the lifestyle
      practices. A significant difference in the occurrence of obesity was found among
      urban and rural children respectively ie. 31 (5.2%) and 13 (2.2%), Zeta cal value
      2.640 > Zeta tab value 1.96). Occurrence of obesity was 50.43 times more among
      adolescents with poor / satisfactory lifestyle practices than with good / very
      good lifestyle practices. A significant association was found between obesity and
      variables like type of family (Chi2 cal = 3.994, p < 0.05), family history of
      obesity (Chi2 cal = 6.168, p < 0.05), and family income (Chi2 cal = 4.123, p <
      0.05) in rural adolescents and between obesity and family history of obesity
      (Chi2 cal = 8.492, p < 0.05) and family income (p = 0.042, p < 0.05) in urban
      adolescents. Adolescent obesity is an emerging health problem and there is need
      for creating awareness among parents, teachers as well as children regarding safe
      dietary habits and active life style.

PMID- 24683757
TI  - Life style modification for patients with ischemic heart disease.
AB  - With a view to assess the effectiveness of lifestyle modification in patients
      with ischemic heart disease, a quasi-experimental study with quantitative
      approach was undertaken on 60 patients of ischemic heart disease. Purposive
      sampling technique was used in selecting the patients. The results showed that
      educating the patients about cessation of smoking, taking proper diet, anxiety
      reduction and counselling helped in preventing the progression of ischaemic heart
      disease.

PMID- 24683758
TI  - Management of osteoporosis among post-menopausal women in a selected hospital of
      Delhi.
AB  - The term 'osteoporosis' describes both a process of decreasing bone density and
      also the clinical outcome of fracture. The research approach for the study was
      the quantitative (exploratory survey research). Majority of postmenopausal women
      (81%) were having osteoporosis, and the remaining 19 percent did not have
      osteoporosis. The findings indicate that there is lack of knowledge among most of
      the postmenopausal women regarding prevention and management of osteoporosis and
      hence there is need to give information to post-menopausal women regarding
      prevention and management of osteoporosis.

PMID- 24683759
TI  - Nurses' perception about a DVD module on 'mental status examination
      demonstration'.
AB  - Computer-based multimedia can improve learning and retention of learnt material A
      video recorded DVD module on role play of mental status examination was
      visualised by 226 nursing students and 133 nursing teachers. Their opinion of the
      DVD on various parameters such as audibility, visibility, clarity, methodical,
      organisation of content, following the principles of psychiatric interview,
      symptom elicitation, therapist behaviour, therapist communication skill and ease
      in understanding revealed that the DVD module was of high quality and could be
      used as a teaching tool

PMID- 24683760
TI  - Effect of structured teaching programme on the knowledge and opinion of nursing
      students towards prevention of mental retardation.
AB  - Mental retardation is a condition of arrested or incomplete development of mind
      which is characterised by impairment of skills manifested during the
      developmental period that contribute to the level of intelligence that is
      cognitive, language, motor and social abilities (WHO). A quasi experimental study
      was conducted at College of Nursing, NIMHANS, Bangalore with the objective to
      assess the effectiveness of structured teaching programme on the level of
      knowledge & opinion of nursing students towards primary prevention of mental
      retardation. The 44, 3rd yr BSc nursing students were selected by purposive
      sampling design. Self administered knowledge questionnaire and opinion scale were
      used as tools. The knowledge questionnaire consisted of four domains: concept,
      prenatal, intranatal, postnatal causes and prevention of mental retardation.
      Opinion scale was prepared as statement. The scale was divided into two domains
      positive and negatively worded. The interpretation was: higher the score, higher
      the positive opinion. The score ranging from 30-75 were negative, 76-90 neutral
      and 91-150 as positive opinion. This study revealed that knowledge score of the
      subjects were significantly increased at p-value 0.001. Opinion score, analysed
      using McNamer's chi-square test, indicated that a significant change occurred
      after structured teaching programme. It is concluded that structured teaching
      programme seems to be highly effective in improving knowledge and opinion towards
      primary prevention of mental disorders.

PMID- 24683761
TI  - Applications of plasma rich in growth factors (PRGF) in dental surgery: a review.

PMID- 24683762
TI  - New Year.

PMID- 24683763
TI  - Why advocate?

PMID- 24683764
TI  - Serve your profession through an Indiana institution.

PMID- 24683765
TI  - EMG guided lateral pterygoid muscle Botox--A injection for chronic
      temporomandibular joint dislocation: 2 patient case report.

PMID- 24683767
TI  - An evaluation of periodontal assessment procedures among Indiana dental
      hygienists.
AB  - Using a descriptive correlational design, this study surveyed periodontal
      assessment procedures currently performed by Indiana dental hygienists in general
      dentistry practices to reveal if deficiencies in assessment exist. Members (n =
      354) of the Indiana Dental Hygienists' Association (IDHA) were invited to
      participate in the survey. A 22 multiple choice question survey, using Likert
      scales for responses, was open to participants for three weeks. Descriptive and
      non-parametric inferential statistics analyzed questions related to demographics
      and assessment procedures practiced. In addition, an evaluation of the awareness
      of periodontal assessment procedures recommended by the American Academy of
      Periodontology (AAP) was examined. Of the 354 Indiana dental hygienists surveyed,
      a 31.9% response rate was achieved. Participants were asked to identify the
      recommended AAP periodontal assessment procedures they perform. The majority of
      respondents indicated either frequently or always performing the listed
      assessment procedures. Additionally, significant relationships were found between
      demographic factors and participants' awareness and performance of recommended
      AAP assessment procedures. While information gathered from this study is valuable
      to the body of literature regarding periodontal disease assessment, continued
      research with larger survey studies should be conducted to obtain a more accurate
      national representation of what is being practiced by dental hygienists.

PMID- 24683768
TI  - Student council presidents and monkey rodeos.

PMID- 24683769
TI  - The potential lifespan impact of gingivitis and periodontitis in children.
AB  - The prevalence of gingivitis in children can be similar to or greater than dental
      caries, but has received much less attention in understanding the long-term
      impact on overall health. Oral health providers must take into consideration that
      the clinical presentation of the gingivitis progression/severity in the primary
      dentition is only evident when the magnitude of the inflammatory cell infiltrate
      approximates the gingival surface reflected by inflamed tissues. Moreover despite
      its relatively benign clinical appearance, the establishment of chronic
      inflammation of the periodontal tissues in childhood may have the potential for
      local tissue destruction leading to periodontitis, and/or create an "at-risk"
      environment in the tissues that could adversely affect the health of these
      tissues across the lifespan. The present manuscript presents some fundamental
      information regarding the characteristics of chronic inflammation in gingival
      tissues of children and adolescents and speculates about the lifetime impact of
      gingival and periodontal infections in childhood on future oral and systemic
      health in the adult.

PMID- 24683770
TI  - Clinical evaluation of desensitizing treatment for incisor teeth affected by
      molar-incisor hypomineralization.
AB  - BACKGROUND: Sensitivity complaints are commonly observed in teeth affected by MIH
      (molar incisor hypomineralization). AIM: This study aimed to evaluate the
      hypersensitivity observed in MIH-affected teeth and the effect of desensitizing
      agents applied with and without ozone to incisors affected by MIH. STUDY DESIGN:
      The first part of the study included 120 teeth from 42 patients with MIH. These
      42 patients included 33 children with 92 incisor teeth with a Vas score of > or =
      30, and these 92 incisors were included in the second part of the study. The
      patients included in the second part were divided into three main groups and six
      subgroups. The main groups included the following: fluoride, CPP-ACP and CPP-ACP
      with fluoride. Each main group was divided into two subgroups: one with ozone use
      and one without ozone use. RESULTS: Girls exhibited significantly more
      sensitivity compared with boys (p < 0.05). There were significant decreases in
      hypersensitivity compared to baseline in all of the groups (p < 0.05). There were
      no differences among the groups at the end of the study (p > 0.05). CONCLUSION:
      The results of this study revealed that gender is an important factor in the
      sensitivity of teeth with MLH. Desensitizing agents effectively reduced the
      hypersensitivity of teeth with MIH. CPP-ACP paste was found to be more effective,
      and ozone therapy prolonged the effect of CPP-ACP paste.

PMID- 24683771
TI  - Utilization of emergency services for non-traumatic dental disease.
AB  - PURPOSE: To identify and characterize children who utilize emergency dental
      services for non-traumatic dental disease. STUDY DESIGN: Caregivers of children
      under 12 years old who seek out emergency services for the treatment of non
      traumatic dental disease will be surveyed regarding their child's current oral
      health status. Patient's clinical data will be obtained and they will be further
      followed for a period of 2 months to determine if they follow-up with
      recommendations for comprehensive dental care. RESULTS: One hundred and ninety
      eight people participated in the study (97% response rate). Eighty-three percent
      of the children were diagnosed with dental caries. Seventy-four percent of
      patients of record presented with an emergency at least once before and 73% had a
      history of one or more broken appointments. Patients with a history of previous
      emergency visits (OR = 3.45, CI = 2.05, 5.81) or a history of missed appointments
      (OR = 2.21, CI = 1.42, 3.58) were significantly more likely to fail to return for
      comprehensive care (P < .01). CONCLUSION: This study shows that those who utilize
      emergency services more than once, or have a history of missed appointments are
      more likely to continue to utilize emergency dental services as their primary
      means for dental care.

PMID- 24683772
TI  - Esthetic and functional recovery of extensively decayed posterior teeth through
      conservative treatment.
AB  - The case exemplifies the combination of two important principles in dentistry: 1)
      the maintenance of pulp vitality by the partial excavation of the contaminated
      dentin followed by the application of a biomaterial; and 2) esthetic and
      functional recovery based on biological restoration. Tooth vitality was confirmed
      two months after pulp treatment and restoration was accomplished with a fragment
      of a tooth extracted from another individual. This method is easy to perform and
      offers esthetic, functional, emotional and social benefits to the patient.

PMID- 24683773
TI  - Biological restoration in a young patient with a complicated crown root fracture
      with an autogenous tooth fragment.
AB  - Crown-root fractures are one of the most challenging trauma cases to treat.
      Reattachment of tooth fragment to a fractured tooth being a simple procedure
      conserves the tooth structure, maintains the natural esthetics value and is thus
      considered as a favorable treatment option. The reattachment procedure using
      composite resin should be considered if the subgingival fracture can be exposed
      to provide isolation after a careful evaluation of the biologic width
      involvement. This case report presents a complicated crown-root fracture of
      permanent maxillary left central incisor, involving the biologic width in an 11
      year-old boy. The traumatized tooth was treated endodontically and reinforced by
      using glass fiber-post. Access to the subgingival margins was gained by electro
      surgery. The fractured fragment was reattached using bonding system and composite
      resin.

PMID- 24683774
TI  - Microbiological assessment of root canals following use of rotary and manual
      instruments in primary molars.
AB  - AIM: To assess the microflora of root canals in primary molars following use of
      rotary NiTi files and conventional hand NiTi and stainless steel files. STUDY
      DESIGN: This randomized clinical trial consisted of a total of 60 first and
      second primary molars requiring root canal treatment, who were selected from
      children aged 5-9 years. Based on type of root canal instrumentation, the teeth
      were randomly assigned to three groups of twenty teeth each; Group A: Rotary NiTi
      files, Group B: Hand NiTi files and Group C: Hand stainless steel files.
      Following administration of local anesthesia, isolation with rubber dam was
      carried out. For the purpose of instrumentation and sampling, the palatal canal
      of maxillary molars and the distal canal of mandibular molars were selected.
      Prior to sampling, the orifices of other canals in these teeth were sealed, so as
      to prevent any contamination. Instrumentation was carried out in each group using
      respective instruments along with intermittent saline irrigation. Root canal
      samples were obtained both before and after instrumentation, using sterile
      absorbent paper points and transferred to a sterile vial with transport fluid.
      Serial dilutions were prepared and cultured on suitable agar media. Both aerobic
      and anaerobic microbial counts were made. Data obtained was subjected to
      statistical analysis using Wilcoxon signed rank test and one-way Analysis of
      variance. RESULTS: In all three groups, there was a significant reduction in both
      aerobic and anaerobic mean microbial count following root canal instrumentation.
      (p < 0.001). CONCLUSION: Rotary NiTi files were as efficient as conventional hand
      instruments in significantly reducing the root canal microflora.

PMID- 24683775
TI  - Salivary pH levels and caries among siblings and parents within families.
AB  - BACKGROUND: High level of caries activity is related to organisms in the dental
      plaque with high acidogenesis capacity. AIM: To test salivary pH in children of
      the same family and compare it with their caries status. To compare pH levels
      between children and their parents. To examine the relationship between pH and
      caries status among children of the same family and their parents. STUDY DESIGN:
      We examined 123 children and adolescents aged 3-18, (73 boys and 50 girls) and 33
      adults, (12 men and 21 women), parents of these children. Caries status was
      examined clinically, using DMF index. Salivary pH measurements were made by a
      digital pH meter. RESULTS: Among adults, increase in patient age led to increased
      DMF (p = 0.005). The higher the pH, the lower the DMF (p = 0.037). Among men, DMF
      was lower by 3 compared to women (p = 0.049). Children's pH correlated with the
      parents' (p = 0.004). Children's DMF correlated to their pH (p = 0.001).
      Children's pH was the best predictor of their DMF (R2 = 0.309, p = 0.001).
      CONCLUSIONS: Among children, the higher the pH, the lower the DMFT. Children's pH
      was the best predictor of their DMF.

PMID- 24683776
TI  - Clinical and microbiological evaluation of the carious dentin before and after
      application of Papacarie gel.
AB  - OBJECTIVE: To evaluate clinically and microbiologically the efficacy of Papacarie
      in the removal of carious dentin in both permanent and primary teeth. STUDY
      DESIGN: Thirty permanent and primary molars with dentinal carious lesions were
      excavated and subjected to clinical and microbiological assessment before and
      after application of Papacarie. The gel was further tested for in vitro
      antimicrobial efficacy against standard cariogenic micro-organisms using agar
      diffusion assay. RESULTS: Papacarie was able to differentiate between infected
      and affected dentin clinically along with high patient comfort during caries
      excavation. The mean time taken for caries removal and restoration was observed
      to be 4.17 +/- 0.40 min. and 8.57 +/- 0.45 min. for permanent teeth and 4.21 +/-
      0.36 min. and 9.24 +/- 0.58 min. for primary teeth. There was a significant
      reduction in the total viable colony forming units from the dentin samples before
      and after application of Papacarie. It was also observed that Papacarie had no
      inhibitory effect on standard cariogenic microorganisms in the agar diffusion
      assay. CONCLUSIONS: Papacarie is an effective caries removal method clinically in
      both permanent and primary teeth. The number of viable microorganisms after
      complete caries excavation using Papacarie still appears to be high and this
      bacterial count should be tackled by a suitable restorative material with potent
      antimicrobial activity.

PMID- 24683777
TI  - Pediatric dental patients' attitudes to rubber dam.
AB  - OBJECTIVES: To explore young patients' experiences of rubber dam (RD) and
      determine how personal and clinical factors may influence opinions. STUDY DESIGN:
      A self-completed questionnaire was developed to capture pediatric patients'
      experiences of treatment under RD in a hospital setting. Patients' acceptance of
      RD and perceptions of how well it was explained to them were recorded on a 10cm
      Visual Analogue Scale (VAS), where zero represented the most negative score. The
      following clinical variables were also recorded: type of RD; procedure
      undertaken; use of local anaesthetic and procedure duration. RESULTS: One hundred
      children (52 male, 48 female) with a mean age of 11.8 years (SD = 2.29; range 7
      17 years) participated Overall, acceptance of RD was satisfactory (mean VAS =
      5.0). Patients were happy with the explanation of why RD was used (mean VAS =
      7.7). The type of RD, use of local anaesthetic, procedure undertaken and duration
      of the procedure did not significantly influence acceptance levels. However RD
      was significantly less acceptable to patients who underwent radiographic
      examination whilst wearing the RD (P < 0.05, t-test). Nearly five times as many
      patients expressed concern at being seen wearing RD when taken to the radiography
      department (39.2%, n = 20/51), compared to those who were reportedly self
      conscious about RD when treated only on the paediatric dentistry clinic (8.2%, n
      = 4/49). CONCLUSIONS: The use of RD appears acceptable physically and
      psychologically to most pediatric patients, however visibility of the RD to
      others was a potential concern to some children.

PMID- 24683778
TI  - Prevalence and risk factors of dental erosion in American children.
AB  - OBJECTIVES: The purpose of this study was to assess the prevalence and
      characteristics of dental erosion in children aged 2-4 years old and 12 years
      old. STUDY DESIGN: 243 subjects were recruited from daycare centers, preschools,
      and grade schools; they received dental examinations assessing their condition of
      dental erosion, including both depth and area of tooth surface loss on four
      maxillary incisors. Questionnaires were given to the subjects to obtain socio
      demographic, oral health behaviors at home, and access to dental care. Dental
      erosion was analyzed and risk factors were assessed using Chi-Square and logistic
      regression analysis. RESULTS: The subjects were 60% Caucasians, 31% Black, 7%
      Hispanic and others were 2%. 34% of children could not get the dental care they
      needed within the past 12 months and 61% of all children brushed their teeth
      twice or more daily. Overall, 12% of study children had dental erosion with 13%
      for 2-4 years old and 10% for 12 years old, with the majority of erosive lesions
      within enamel. Family income (OR 3.98, p = 0.021) and acidic fruit juice
      consumption (OR 2.38, p = 0.038) were significant risk factors for dental
      erosion, even after controlling for other factors, such as source of drinking
      water and oral hygiene using logistic regression analysis. CONCLUSIONS: Dental
      erosion is a relatively common problem among the children in this study and it is
      seen as a multi-factorial process.

PMID- 24683779
TI  - Shear-bond strength of a new self-adhering flowable restorative material to
      dentin of primary molars.
AB  - OBJECTIVE: The aim of this study was to evaluate the shear bond strength to
      dentin of primary molars of a new self-adhering flowable resin composite with two
      ionomer-based cements and one flowable resin composite in combination with two
      different adhesive systems. STUDY DESIGN: Fifty primary molars were grinded on
      the occlusal surface to obtain flat dentin substrate and randomly divided into 5
      groups (n = 10): OFL:Phosphoric Acid/Optibond FL/Premise Flow; OAO:Optibond All
      In-One/Premise Flowable; II:Polyacrylic Acid/Fuji II; IX:Polyacrylic Acid/Fuji
      IX; V:Vertise Flow. Cylinders (3mm diameter - 5mm height) of restorative material
      were built-up in three increments over the dentin surfaces. A shear load was
      applied until failure. Bond strength values were statistically analysed with
      Kruskall-Wallis ANOVA followed by Dunn's test (P < .05). Differences in failure
      mode distribution were assessed with Chi-square (P < .05). RESULTS: OFL and OAO
      recorded significantly higher bond strengths than the other groups. Adhesive
      failures were evident in all groups except OFL and OAO, in which also cohesive
      failures in dentin were observed. CONCLUSIONS: Vertise Flow established on
      primary dentin bond strengths values similar to those of glass ionomer cements
      routinely used for restorations of primary teeth. The combination of flowable
      resin with etch-and-rinse or all-in-one adhesives obtained higher bond strength
      values, thus involving a more complex handling.

PMID- 24683780
TI  - Presence of oral bacterial species in primary endodontic infections of primary
      teeth.
AB  - OBJECTIVE: Knowledge of the microbial composition of deciduous endodontic
      infections is limited. This study aimed to evaluate the presence of the 10 oral
      bacterial species in samples from primary tooth root canals by using microarray
      technology and to determine the association of these organisms with clinical
      conditions. STUDY DESIGN: The samples were collected from 30 root canals of
      primary teeth with primer infection. The bacterial composition of the samples was
      semi-quantitatively defined using a microarray system (Parocheck). RESULTS: All
      the tested species were detected in the samples. Fusobacterium nucleatum was the
      most frequently isolated bacterium (96.7%), followed by Prevotella intermedia
      (86.7%), Parvimonas micra (83.3%), Treponema denticola (76.7%) and Tannerella
      forsythia (66.7%). These bacteria were also present in high levels. All pairs of
      bacterial species were positively associated (RR > 1), except Pintermedia and P >
      micra. On average, five species (range:3-8) were detected per amplified sample.
      Root canals of teeth with > 5 different species were statistically associated
      with periapical radiolucency (P = 0.049). CONCLUSIONS: Primary teeth with
      endodontic infections show a highly diverse variety of bacteria, in which the
      most prevalent specie are present in high proportions. The well-directed use of
      the improved microarray technology will provide additional valuable information
      for causative factors associated with endodontic diseases, helping to develop
      more successful antibacterial or anti-inflammatory treatment strategies.

PMID- 24683782
TI  - Severe congenital hypoglossia: a case report.
AB  - Hypoglossia is referred to a small volume and/or size of the tongue. It is a rare
      congenital condition caused by failed embryogenesis of the lateral lingual
      swellings and tuberculum impar during the fourth to eighth weeks of gestation.
      The anomaly has often occurred in association with limb abnormalities and various
      syndromes, and it affects facial and mandibular growth. The present report
      describes a case of severe congenital hypoglossia in a female infant, her
      systemic and dentofacial features, and the initial management.

PMID- 24683781
TI  - Parotid gland enlargement in pediatric HIV population.
AB  - OBJECTIVES: To establish the significance of parotid enlargement, state
      frequency, cytological features and effect of antiretroviral therapy (ART) on
      parotid enlargement among a pediatric HIV population. STUDY DESIGN: A 6 month
      cross sectional survey that utilised clinical features, serial immunological
      indices and fine needle aspiration cytology. RESULTS: 287 HIV positive children
      were seen at special paediatric clinic of the University College Hospital,
      Ibadan, Nigeria, 114 (39.7%) had oral features and among these 24 (8.4%) had
      parotid involvement comprising of 10 males and 14 females. The overall mean age
      was 43.4 + 39.7 months compared with 59.6 + 36.5 months in the parotid
      enlargement group (p = 0.03). Mean ages of parotid enlargement and non
      enlargement group was significantly different (p = 0.03). The mode of
      transmission was vertical in (91.7%), 87.5% was bilateral (87.5%) and (75%)
      presented as a syndrome state with generalised lymphadenopathy. The predominant
      cytology was lymphoid hyperplasia (62.5%). ART resulted in marked clinical
      reduction in all the cases and statistically significant improvement in serum
      indices of CD4 count, CD4% and viral load (p = 0.001, 0.000 & 0.009
      respectively). CONCLUSION: HIV positive children often present with bilateral
      parotid enlargement and the syndrome state with classical clinical and
      cytological features of lymphoid hyperplasia predominated. ART resulted in
      satisfactory reduction of the swellings in most of the cases with no need for
      further intervention.

PMID- 24683783
TI  - Buccal midazolam spray as an alternative to intranasal route for conscious
      sedation in pediatric dentistry.
AB  - OBJECTIVES: To evaluate the acceptance of midazolam spray through buccal route as
      compared to intranasal route and compare the efficacy of the drug through both
      the routes. STUDY DESIGN: 30 patients aged 2-8 years with Grade I or II Frankl's
      Behaviour Rating Scale were selected who required similar treatment under local
      anesthesia on two teeth. Midazolam spray was administered randomly through buccal
      or intranasal routes for the two appointments. Scoring was done for the
      acceptance of drug and Houpt's score was recorded for the behaviour of patients
      during the treatment. RESULTS: Acceptance of drug through buccal route was
      significantly better than the intranasal route (p < 0.05) but no statistically
      significant difference was found in the behaviour scores for the two routes of
      administration (p > 0.05). CONCLUSION: Midazolam spray can be effectively used
      through the buccal mucosa in children who give poor compliance with the
      intranasal administration.

PMID- 24683784
TI  - Prevalence of salivary Streptococcus mutans serotype k in children undergoing
      congenital heart surgery.
AB  - OBJECTIVE: The prevalence of Streptococcus mutans serotype k, which was
      speculated that might be associated with the development of cardiovascular
      diseases, has been reported in adult cardiovascular surgery patients. There is no
      information about presence of serotype k in children with cardiac disease. The
      aim of this study was to determine the salivary prevalence of S. mutans serotype
      k in children with congenital heart disease. STUDY DESIGN: Salivary samples of 25
      patients undergoing elective surgery for congenital heart defects with
      cardiopulmonary bypass and an age and gender matched control group of 25 healthy
      children were enrolled in the study. Species-specific 16SrRNA gene sequences were
      used for S. mutans and serotype-specific rgpF gene sequences were used for S.
      mutans serotype k determination in stimulated saliva samples. RESULTS: S. mutans
      was detected in 19 (76%) of the study and 15 (60%) of the control children. The
      difference was not shown to be statistically significant. Serotype k was
      determined from 3 (12%) of the study group, while it was not determined from the
      samples of the control group. CONCLUSIONS: Our results indicate that those
      children with congenital heart disease may possess S. mutans serotype k in oral
      cavity at a higher frequency as similar with the adult cardiac surgery patients.

PMID- 24683785
TI  - Mandibular condylar aplasia treated with a functional approach.
AB  - Mandibular condyle aplasia is a congenital or acquired malformation, which can be
      or not associated to some head and neck syndromes. Its treatment involves either
      a surgical approach or a more conservative treatment with orthopedic functional
      appliances. This clinical report presents a case of mandibular condyle aplasia
      treated with a modified KLAMT functional appliance, after a surgical procedure
      failed to stimulate mandibular condyle remodelling. The successful results
      presented here, with an orthopedic functional approach, support treatment with
      functional appliances as an alternative, producing similar results to those
      reported with surgery. Therefore, functional appliances are proposed as a valid
      alternative to stimulate mandibular condyle remodelling in patients with
      mandibular condyle aplasia. Treatment provided at an early age appears to be
      relevant for a successful result.

PMID- 24683786
TI  - [Out of the blue].

PMID- 24683787
TI  - [Premature infants: fragile life on the brink].

PMID- 24683789
TI  - [Professionalization in nursing: the path is still far from completed].

PMID- 24683788
TI  - [COPE at the Island Hospital: training program for parents].

PMID- 24683790
TI  - [Interview with Barbara Datwyler. "A better profession society cannot wish for"].

PMID- 24683791
TI  - ["Young SBK": in the SGT/TG/AI/AR section: "we need to voice our concerns"].

PMID- 24683792
TI  - [Anesthesia nursing: hypothermia in the perioperative setting].

PMID- 24683793
TI  - [Clinical assessment for nursing practice - 3: Maintaining the health of family
      caregivers].

PMID- 24683794
TI  - [New health professions regulation: "not all demands considered"].

PMID- 24683795
TI  - [Venous ulcus cruris: the higher the pressure, the better the healing].

PMID- 24683796
TI  - [Survey of nursing education graduates: with professional identification into
      nursing care].

PMID- 24683797
TI  - [Challenging behavior in dementia: nursing care instead of drugs].

PMID- 24683798
TI  - [End of life care in pediatrics: when children die].

PMID- 24683799
TI  - [Everything with finesse].

PMID- 24683800
TI  - [The child and its family in pediatrics: listening to the needs of parents].

PMID- 24683801
TI  - [Recent graduate: "I am obliged to ask many questions"].

PMID- 24683802
TI  - [Intensive care units: objective: zero pain!].

PMID- 24683803
TI  - [Swiss DRG: CHOP codes for complex nursing care treatments: nursing enters DRG].

PMID- 24683804
TI  - [Conditions of war or conflict: weapons of mass destruction and their impact].

PMID- 24683805
TI  - [The will to be born].

PMID- 24683806
TI  - Learning from the Oslo Congress.

PMID- 24683807
TI  - Hospital quality: a product of good management as much as good treatment.
AB  - In Norway, as in most countries, the demands placed on hospitals to reduce costs
      and improve the quality of services are intense. Although many say that improving
      quality reduces costs, few can prove it. Futhermore, how many people can show
      that improving quality improves patient satisfaction. Diakonhjemmet hospital in
      Norway has designed and implemented a hospital management system based on lean
      principles and the PDCA (Plan-Do-Check-Act) quality circle introduced by WE
      Deming (Deming 2000). The results are quite impressive with improvements in
      quality and patient satisfaction. The hospital also runs at a profit.

PMID- 24683808
TI  - The effects of preventive mental health programmes in secondary schools.
AB  - The author wanted to test the effects of preventive mental health programmes in
      schools and established a longitudinal study with a test group and a control
      group, using Solomon's method. Data was collected through questionnaires prior to
      intervention and at 1, 6, 12, and 24 months after the intervention. The size of
      the effect on the various indices were estimated in terms of (a) differences in
      improvement of total percentage scores and (b) Cohen's d. From to to t1, t2 and
      t3 the intervention group showed significantly greater progress in six out of
      seven knowledge indexes, and 12 months later we found significant effects on the
      level of mental health problems.

PMID- 24683809
TI  - Health and health systems performance in the United Arab Emirates.
AB  - In the early 2000s, the United Arab Emirates (UAE) had good levels of health and
      its health system was ranked twenty-seventh in the world by the World Health
      Organization. Since that time, to further improve the situation and to address
      cost and quality challenges, the UAE has embarked on an ambitious programme of
      health system reform. These reforms have focused on the introduction of private
      health insurance and encouraging the growth of private health provision. In these
      areas there have been impressive achievements but while it is too early to say
      whether these reforms are succeeding some anxieties are emerging. These include
      the rising cost of services with no obvious improvement in outcomes, a growth in
      hospital provision that may not best meet the needs of the population, rising
      levels of chronic disease risk factors and an insuffcient focus on public health
      services, public health leadership, health work-force planning and research.

PMID- 24683810
TI  - Testing payment-for-performance in French acute care hospitals: a point of view
      from the French Federation of Comprehensive Cancer Centres.
AB  - In 2004, France began a diagnosis related groups-based financing system for both
      public and private acute care hospitals. France opted for a mix of financing
      systems with over 80% of funding based on diagnosis related groups (DRG). After
      seven years of DRG-based financing, the French government is testing a payment
      for-performance system in acute care hospitals, based on the USA experience.
      France is currently fine-tuning this model. So far, observations have raised
      doubts as to whether this approach will improve the value of health care in
      French hospitals: the budget appears insufficient, the quality of the available
      indicators is poor and the model is complex. However, it has focused attention on
      the question of health care quality.

PMID- 24683812
TI  - Making medical and research strategic choices: a case study from Antwerp
      University Hospital.
AB  - In the early 2000s, Antwerp University Hospital witnessed drastic changes to its
      circumstances: large general hospitals in the area were marged and the university
      hospital was privatized and separated from the University of Antwerp, which is
      primarily a teaching university. In light of these developments, Antwerp
      University Hospital adopted a strategy of transforming itself into a more
      specialized centre of expertise. Three fields of specialization were selected by
      the management as centres of excellence, based on clinical and scientific
      indicators. In a renewed synergy with the university, a clinical research centre
      was established to direct joint translational research. The core facilities for
      translational research were also selected in limited numbers based on strengths
      and opportunities. After six years, the centre had demonstrated that small, more
      specialized institutions can also be successful.

PMID- 24683811
TI  - The CASSANDRE Project: automated alerts for optimal coding of diagnosis and
      interventions.
AB  - As of 1 January 2012,all Swiss hospitals have had to charge acute somatic care
      hospitalization according to the Swiss disease related group (DRG) System. In
      this system, hospital bills are based on the discharge summaries. Coders analyze
      these in order to identify diagnostic and interventional codes. These codes are
      used by the system grouper to determine a specific DRG code and cost-weight. The
      amount to be charged per episode is based on this cost-weight. Since acute care
      billing relies on discharge summaries and knowing that these are incomplete, our
      aim was to inprove the completeness of these documents by automatically detecting
      pathologies that should have been coded and charged. We also aimed to help
      improve the selection of the main diagnosis. We have implemented algorithms for
      the automatic detection of pathologies that directly inform the coders whilst by
      passing the physician. Final validation of the new pathologies remains with the
      physician. Our results are very encouraging from a financial point of view.

PMID- 24683813
TI  - Disaster resilient hospitals: an essential for all-hazards emergency
      preparedness.
AB  - Hospitals and health facilities play a crucial role in providing health services
      for their communities, in particular during crises and emergencies. Well prepared
      and disaster resilient hospitals are therefore essential to be able to meet the
      increased demands for life saving services in large scale emergencies, which can
      quickly overwhelm the surge capacity and functional safety of the hospitals and
      of the health system at large. The World Health Organization (WHO) has developed
      tools like the Hospital Safety Index, the WHO Regional Office for Europe's
      Hospital emergency response checklist and Toolkit for assessing health-system
      capacity for crisis management to assisst emergency managers to assess the
      structural and functional safety of health facilities, to enhance emergency
      preparedness to respond effectively to the most likely disaster scenarios and to
      strengthen overall health system preparedness with an all-hazards approach
      through fostering the crisis management capacities of hospitals. This article
      briefly introduces these WHO tools and provides an overview of their
      implementation and roll out in Member States of the WHO European Region.

PMID- 24683814
TI  - Global health care trends and innovation in Korean hospitals.
AB  - Health care is one of the most significant global issues. The Korean health care
      systems, which has both good and bad features, is grabbing international
      attention because of its cost effectiveness. However, it is also facing a lot of
      challenges such as a rapidly ageing population, increases in expenditure and too
      many competing acute hospitals. Therefore, many Korean hospitals have been trying
      to find innovative ways to survive. This article introduces some possible answers
      such as expansion and consolidation strategies, quality assureance, converging
      ICT and health care, attracting foreign patients, research-driven hospitals,
      public-private partnerships and a focus on service design and patient experience.

PMID- 24683815
TI  - [MIF in head and neck cancer: a new therapeutic target ?].
AB  - Macrophage migration inhibitory factor is a critical proinflammatory cytokine
      produced by cells of innate and adaptive immune system. MIF plays a key role in
      cell cycle regulation and in the pathogenesis of many cancers. Recently, MIF has
      been studied in the upper aerodigestive tract cancer for its involvement in tumor
      progression, invasion, proliferation and cell motility. In addition, MIF appears
      to be a mediator in angiogenesis and in the development of metastasis and
      locoregional lymph node, which are often associated with a poor prognosis. The
      mechanisms of action responsible for MIF involvement in tumor progression are not
      completely elucidated. However, the main effects of MIF are mediated by the CD74
      receptor. MIF binding to its receptor is responsible for the activation of
      several signaling pathways (ERK1/2 - MAPK, JAB1 - CSN5, PI3K - Akt), the
      inhibition of p53 and the stimulation of angiogenic factors including VEGF and IL
      8. The overexpression of MIF also causes a reduction of the anti-tumor activity
      of the immune system. Finally, MIF could be an interesting biomarker in the
      diagnosis and monitoring of upper aerodigestive tract cancers. In this paper, we
      assess the state of knowledge of MIF involvement in upper aero-digestive tract
      cancers and we analyze the therapeutic perspectives.

PMID- 24683816
TI  - [Prognostic value of sentinel lymph node in Merkel cell carcinoma of the head and
      neck].
AB  - INTRODUCTION: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor.
      The aim of our study was to analyze the prognosis of patients operated on for CCM
      and having no lymph node involvement after analysis of sentinel lymph node (SLN).
      MATERIAL AND METHOD: This was a retrospective study of 10 cases of CCM stage I or
      II who received the SLN technique in our institution between 2003 and 2010.
      RESULTS Among the 10 patients, 7 had an identification of at least one SLN, among
      which the node could be surgically removed in 6 cases. In cases of failure of SLN
      technique, a neck dissection +/- parotidectomy was performed. No lymph node
      metastasis was found in our series. Mean follow-up was 38 months. The overall
      survival rate was 100% at 2 years and 50% at 5 years. The Disease-free survival
      was 85% at 2 and 5 years. CONCLUSION: Our results show that the technique of
      sentinel lymph node is a reliable tool for evaluating nodal status of patients
      with CCM and that pN0 patients have a good prognosis.

PMID- 24683817
TI  - [Diagnosis and therapeutic pathways in head and neck cancers].
AB  - BACKGROUND: Cancers of uppers aero-digestives tracts represent, infrequency, the
      5th cancer in the French population. Most of them (about 70%) are diagnosed at an
      advanced stage (stage III or IV) while they are associated with a poor prognosis
      (only 40% five year survival). The objective of our study was to analyze the care
      pathway of patients with cancers of uppers aero-digestives tracts in order to
      target efforts to improve the survival of these patients. METHODS: It was a
      descriptive and retrospective study, on medical files, on the health care pathway
      of patients with cancers of uppers aero-digestives tracts cared in the Head and
      Neck surgery department of Val de Grace in Paris and Percy in Clamart between
      January 2004 and December 2006. The patients were adults with squamous cell
      carcinoma of uppers aero-digestives tracts. RESULTS: One hundred thirty-eight
      files of patients were analyzed. Fifty-five percent of patients were diagnosed at
      an advanced stage. On average patients have waited two months and twenty-one days
      before consulting a doctor for the first time. The time interval between the
      specialist consultation and the start of treatment was on average 7 weeks. The
      overall 5-year survival rate was 61%. CONCLUSION: Squamous cell carcinoma of
      uppers aero-digestives tracts remains serious and has a poor diagnosis, even in a
      population with a high social-cultural level. The long time interval before the
      first consultation may be reduced by improving health education among the general
      practitioner (primary and secondary prevention), and by establishing health care
      public campaigns. This would allow earlier diagnosis, more conservative
      therapeutic opportunities and therefore a better prognosis.

PMID- 24683818
TI  - PET/CT in the management of metastatic cervical lymphadenopathy from unknown
      primary site: a seven years retrospective study.
AB  - OBJECTIVES: To evaluate the accuracy of PET/CT for the diagnostic evaluation of
      patients presenting cervical node metastasis of suspected unknown primary;
      furthermore to understand its relative clinical utility and relevance when
      compared to classic endoscopic investigation approach. MATERIALS & METHODS: A
      retrospective study was pursued, collecting information from clinical files of
      all patients who presented to the Portuguese Institute of Oncology - Oporto, from
      January 2005 to December 2011, with cervical node metastases whose primary hadn't
      been found, despite clinical examination and standard imaging (CT scan or MRI)
      and therefore were submitted to a PET/CT. Among those presenting with non
      supraclavicular metastasis patients were subsequently analyzed according to:
      histopathology; those who performed examination under anaesthesia (EUA) for
      biopsies either before of after PET/CT. RESULTS: Eighty nine patients were
      included in the study. Detection rate was 32.6% with no statistically difference
      between those with supraclavicular metastases and those with metastases in higher
      cervical levels (p = 0.24). In this last group (n = 76), 43% patients had had
      PET/CT and an endoscopy associated with biopsies of the upper aerodigestive tract
      in different orders, to complete diagnostic workup in cases where the first
      performed was inconclusive. No statistically difference was found between these
      two methods (p = 0.25). Most of noticed false negatives were microscopic lesions
      located deep in the palatine tonsils. CONCLUSIONS: PET/CT showed to be an useful
      tool when searching for primary tumours whether metastasis were supraclavicular
      or located in higher levels of the neck. Despite its good accuracy and detection
      of tumours previously undetected by EUA with biopsies (missed mainly due to
      sampling error), up-front negative scan shouldn't preclude performing
      endoscopies. Being evident that both tools are helpful. It was not possible in
      this study to find any evidence that could show which one of these two exams
      should be performed first.

PMID- 24683819
TI  - [Epidemiology of paediatric emergencies in ENT].
AB  - OBJECTIVE: To assess the prevalence and severity of pediatric emergencies in ENT
      in Casablanca. MATERIAL AND METHODS: This is a retrospective study over two years
      from January 1st 2010 to December 31, 2011, covering 2220 pediatric
      othorhinolaryngology emergencies observed in the emergency department of the "20
      August Casablanca" hospital. RESULTS: Males predominate and account for 72.25%
      compared to 27.74% of girls. The mean age was 7.5 years ranging from 03 months to
      15 years. Five pathologies top the list; head and neck wounds (28.11%), foreign
      bodies (21.62%), infectious emergencies (21.57%), blunt trauma (16.39%), and
      finally hemorrhages from natural orifices (11.22%). CONCLUSION: This study
      assessed the prevalence and severity of ENT emergencies in children in
      Casablanca.

PMID- 24683820
TI  - Late metastasis from renal cell carcinoma to the thyroid and nasal cavity: report
      of a case.
AB  - Multifocal cervico-facial metastases are very rare. Medical history of the
      patient and clinical context make easier the diagnosis. A 54-year-old woman
      presenting with a nasal obstruction, was referred to our department. She had a
      past medical history of an operated renal cancer 12 years ago and a right
      hemithyroidectomy 30 years ago. Clinical examination revealed a polypoid lesion
      obstructing the right nasal cavity and a thyroid goiter. Fine-needle aspiration
      was positive for a renal metastasis. Computed tomography confirmed the nasal
      lesion without bone destruction and a cervical cystic lesion into the left
      thyroid lobe. Completion thyroidectomy and polyp excision were performed. The
      final histologic examination revealed a metastasis from a renal cancer. The
      association of intra-thyroid and nasal cavity metastases is uncommon and not
      related in the literature, the practitioner must suspect the diagnosis if the
      patient had a thyroid tumor, a suspicious nasal lesion and a past history of
      cancer. The surgical management is recommended for isolated metastasis to the
      nasal cavity and the thyroid gland especially in renal cancer.

PMID- 24683821
TI  - [Two cases of primary malignant melanoma of the larynx: a rare pathology].
AB  - INTRODUCTION: Primary malignant melanoma of the larynx is a very rare entity.
      There are less than sixty cases described in the literature. Through both cases,
      we describe and discuss the clinical management of melanoma of the larynx.
      CLINICAL CASES: Two men aged 80 and 61 years were supported for MPL. The tumor
      was revealed by persistent dysphonia for the first. For the second, it was a
      second melanoma of laryngeal location. In both cases it was performed a total
      laryngectomy extended to the first tracheal rings with bilateral lymphadenectomy
      associated with adjuvant radiotherapy. DISCUSSION: Excision margins with
      oncological safety are necessary to except a curative surgery. Still
      controversial, the adjuvant radiotherapy seems to provide a benefit in terms of
      local control. The place of targeted therapies remains unclear. However, no
      prognostic factor is currently clearly identified for this disease. CONCLUSION:
      Rare tumor, the MPL is associated with a very poor prognosis. Resective surgery
      followed by adjuvant radiotherapy is for us the treatment of choice.

PMID- 24683822
TI  - Laryngeal paraganglioma mimicking a laryngeal haemangioma.
AB  - Paraganglioma are uncommon neuroendocrine tumours arising from extra-adrenal
      chromaffin cells of the autonomic nervous system. In the head and neck region,
      these neoplasms most commonly arise from the carotid body, the vagus nerve, and
      the jugulotympanic area. We present the case of a 69-year-old woman who suffered
      from dyspnoea and dysphonia for six months. A biopsy diagnosed a laryngeal
      haemangioma and a resection of the tumour was performed using supraglottic
      pharyngolaryngectomy. Definitive histopathological examination revealed a
      laryngeal paraganglioma. Laryngeal paraganglioma and haemangioma must be evoked
      when confronted with a submucosal vascular laryngeal tumour. In such cases
      biopsies should be avoided. Exhaustive imaging is a key factor in the diagnosis
      and should include an MRI and an arteriography in order to rule out other
      differential diagnoses. To our knowledge this is the first case focusing on this
      issue.

PMID- 24683823
TI  - [Post intubation collected septic cricoarytenoid arthritis: case report].
AB  - We report a rare case of post intubation cricoarytenoid arthritis. A 18-year-old
      man admitted to emergency was easely intubated for 14 days for a non neck injury.
      Sixty-six days after intubation, he consulted for severe odynophagia with
      dyspnoea. Nasofibroscopic examination revealed a right arytenoid granuloma with
      oedema and inflammation, and bilateral arytenoid immobility. There was evidence
      on the CT scan of cricoarytenoid arthritis with fluid accumulation. Antibiotic
      treatment and two punctures for drainage allowed healing. There were cricoid and
      arytenoid calcifications. The patient recovered total and stable laryngeal
      mobility and function. This case is unusual, with features unlike those
      previously reported: intubation being the probable cause, the unusual clinical
      presentation with painless cricoid palpation, and the contrast between imaging
      findings during follow-up and the evolution under treatment. Indeed, there was an
      apparent discrepancy between the favourable clinical course and the CT-images
      revealing calcifications.

PMID- 24683824
TI  - [Image of the month. The Chatterjee effect].

PMID- 24683825
TI  - [Clinical study of the month: depressive pseudo-dementia].
AB  - We report the case of a man aged 62 suffering from a known type I bipolar
      disorder and referred by his attending psychiatrist because of a state of
      spatiotemporal disorientation, confusion and prostration evoking significant
      neurologic impairment. The interest of this case report is in the use of the 18
      FDG PET-Scanner, which is increasingly widespread in clinical psychiatry, to
      support the differential diagnosis between a psycho-organic pathology like
      dementia or a functional psychiatric pathology like depressive pseudo-dementia
      (also named melancholic dementia), in which some patterns of dysfunction can now
      be identified by functional imaging.

PMID- 24683826
TI  - [Environmental effects on the stratum corneum].
AB  - The frontier between the human body and the environment is largely represented by
      the stratum corneum. It is obvious that the skin aspect on some body sites
      appears dry and rough in some predisposed individuals during winter season. The
      reductions in the outdoor temperature, ambient moisture and dew point are the
      main physical factors involved in this process. We present the aspects seen under
      ultraviolet light and scanning electron microscopy.

PMID- 24683828
TI  - [Implementation of a massive transfusion protocol in an emergency department].
AB  - We present here the massive transfusion protocol implemented in our institution
      in 2013. It will improve our management of critical massive bleeding, a situation
      which is rare in in our hospital, but carries a high mortality risk.

PMID- 24683827
TI  - [Narcolepsy-cataplexy today].
AB  - Diagnostic criteria and pathophysiology of narcolepsy-cataplexy have evolved
      considerably over the last 10 years. The main cause, already mentioned in a
      previous paper, in the Revue Medicale de Liege (65), in 2002, is based, in human
      beings, on a destruction of specific cells located in the lateral and posterior
      part of the hypothalamus (the perifornical nuclei, containing some 70,000
      neurons), producing peptides which stimulate the central nervous system; they are
      called hypocretins or orexins. The role of autoimmunity in their disappearance
      becomes more evident. The treatment is simplified, but remains symptomatic. It is
      mainly based on Sodium Oxybate or Gamma-Hydroxybutyrate, syrup, prescribed for
      the night. The authors report on their own experience in this regard and on
      future therapeutics more targeted towards the cause of the disease.

PMID- 24683829
TI  - [The history of the pituitary gland: evolution of mental representation and
      concepts over time].
AB  - The hypothalamo pituitary axis, as the true conductor of the endocrine orchestra,
      is frequently involved in a large variety of pathological conditions such as
      acromegaly, behavioral disorders, obesity or dwarfism. It is paradoxical to note
      that, in spite of its importance, this system has been almost ignored by the
      physiologists of the late centuries. From the physiological conceptions of the
      physicians and philosophers of antiquity to the theories of the medieval and of
      the Renaissance physiologists, we will try to understand why the role of
      pituitary remained so long unrecognized.

PMID- 24683830
TI  - [A case of autoinjection of vaseline under penis skin].
AB  - We report the case of a 24-year-old rumanian patient who came to the emergency
      department complaining of glans penis pain and tight phimosis; he claimed to have
      undergone an injection of vaseline under penis skin. We review the literature on
      various nonmedical practices of penile foreign body injection to enlarge and
      thicken the penis.

PMID- 24683831
TI  - [Alpha-2 adrenoreceptor agonists in anaesthesia and intensive care medicine].
AB  - Alpha-2 adrenoreceptor agonists have long been used in the treatment of arterial
      hypertension. However, in that indication they have progressively been replaced
      by antihypertensive drugs with a more interesting therapeutic profile.
      Nonetheless, pharmacological activation of alpha-2 adrenoreceptors leads to a
      variety of clinical effects that are of major interest for anaesthesia and
      intensive care practice. Indeed, the sedative and analgesic properties of alpha-2
      adrenoreceptor agonists allow a reduction of hypnotic and opioid needs during
      general anaesthesia. In addition, they induce a down-regulation of the level of
      consciousness comparable to that of natural slow-wave sleep during post
      anaesthesia and intensive care unit stay. These drugs may also prevent some
      deleterious effects of the sympathetic discharge in response to surgical stress.
      Furthermore, alpha-2 adrenoreceptor agonists are potent adjuncts for locoregional
      anaesthesia. In this article, we will summarize the most frequent applications of
      alpha-2 adrenoreceptor agonists in anaesthesia and intensive care medicine. We
      will focus on the clinical data available for the two most representative
      molecules of this pharmacological class: clonidine and dexmedetomidine.

PMID- 24683832
TI  - [Lixisenatide (Lyxumia), a new agonist of glucagon-like peptide-1 receptors with
      a predominant postprandial action].
AB  - Lixisenatide (Lyxumia) is a new agonist of Glucagon-Like Peptide-1 (GLP-1)
      receptors that is indicated in the treatment of type 2 diabetes, in one single
      subcutaneous daily injection of 20 microg. It exerts an incretin effect by
      stimulating insulin secretion after a meal while inhibiting glucagon secretion,
      both in a glucose-dependent manner, which limits the risk of hypoglycaemia. In
      addition, it slows down gastric emptying after a meal, which contributes to
      reduce postprandial hyperglycaemia, especially after breakfast. Lixisenatide is
      currently reimbursed in Belgium after failure of a dual therapy with metformin
      and a sulfonylurea but also in combination with a basal insulin (with or without
      oral antidiabetic drugs). The latter interesting combination should tackle
      fasting glycaemia with basal insulin (after appropriate dose titration) and
      postprandial hyperglycaemia with the GLP-1 receptor agonist in a complementary
      manner. The consequence is a further improvement of glycated haemoglobin
      (HbA(1c)) varying between 0.3 and 0.9% in various studies comparing lixisenatide
      versus placebo. As other compounds of the class, lixisenatide induces a small
      weight reduction, which contrasts with the weight gain commonly observed with
      other antidiabetic medications (including insulin). Further studies should
      demonstrate the effects of lixisenatide on vascular complications and overall
      prognosis of patients with type 2 diabetes.

PMID- 24683833
TI  - [Diagnosis and assessment of hypoglycemia in patients with diabetes mellitus].
AB  - Hypoglycaemic episodes are rather common among diabetic patients, especially
      those treated with sulfonylureas or insulin (more in type 1 than in type 2
      diabetes). The presentation of hypoglycaemia may considerably vary from patient
      to-patient and from time-to-time in a given patient. With the illustration of a
      clinical case, we will describe the characteristics of the three main types of
      hypoglycaemia: severe hypoglycaemia (with or without coma), symptomatic
      hypoglycaemia (with or without confirmation) and asymptomatic hypoglycaemia
      ("hypoglycaemia unawareness") discovered as a low blood glucose measurement. We
      will also briefly analyse the reasons of such differences and the potential
      clinical consequences that these three main types of hypoglycaemia may exert in
      the real life of diabetic patients.

PMID- 24683834
TI  - [For the past few years, universities have been confronted with unprecedented
      political intrusions in the curriculum].

PMID- 24683835
TI  - [Sinonasal inverted papilloma: our experiences of diagnostic and surgical care in
      Cote d'Ivoire].
AB  - OBJECTIVE: To present our experience of the diagnostic and surgical care of sino
      nasal inverted papilloma. MATERIAL AND METHOD: Retrospective study over 14 years
      (1996-2010) realised in the ENT departments in Cote d'Ivoire. Thirteen inverted
      papilloma confirmed and operated, after computed tomography, were included (7 men
      and 6 women, from 8 to 55 years old). RESULTS: The nasal obstruction was the main
      symptom. Twelve inverted papilloma correspond to Krouse stage T3, and 1 case T4.
      Surgical removal was performed by lateral rhinotomy (8 cases), Caldwell-Luc (4
      cases) and De Lima (1 case). Squamous cell carcinoma was associated in 1 case.
      Recurrence with malignant transformation was observed in 1 case. CONCLUSION:
      Surgery by external approach allowed to obtaining satisfactory results. It stays
      of current events in our countries under equipped. Histopathological examination
      of the surgical specimen must be compulsory.

PMID- 24683836
TI  - [Postpartum depression: correlations and predictive factors].
AB  - Post-partum depression (PPD) belongs to the depressive spectrum consecutive to a
      pregnancy. It is important to detect it as soon as possible to avoid non
      negligible consequences for the mother, the new born and close relatives. It some
      cases, PPD may give way to post-partum psychosis, a psychiatric emergency. The
      present study splits 88 women in two groups, within days of delivery, as a
      function of their score at the Edinburgh postnatal Depression Scale (EPDS), an
      internationally validated scale which predicts future episodes of PPD. The two
      groups are then compared to a series of open items, obtained by personal
      interview, with the objective to better differentiate psychological and
      historical data giving way to this condition. Among the women, 27.3% had a score
      on the EPDS > or = 12 which is higher than what is generally encountered in the
      literature. The main results of this study are: 1) the higher percentage in the
      at risk group of women living with a significant other; 2) the presence of
      psychic or somatic issues during the pregnancy; 3) the feelings of negligence by
      the immediate environment; 4) auto-depreciative tendency, the ill-fulfilling of
      maternal function. These items are easily detectable if a little more attention
      was dedicated to young mothers soon after delivery.

PMID- 24683837
TI  - [Can we prescribe lithium during pregnancy? Summary of a controversy].
AB  - Lithium is the standard treatment for bipolar disorder. It has long been contra
      indicated during pregnancy because of its teratogenicity, especially regarding
      cardiac anomalies. More recent epidemiological studies show that the teratogenic
      risk of lithium has been overestimated in the past. When caring for a pregnant
      bipolar woman, physicians should consider the risk of fetal exposure to a mood
      stabilizer but also the risk of relapse if the treatment is interrupted. We have
      conducted a literature review on this subject. In the second part of the article,
      we have looked at the authors' recommendations about possible administration of
      lithium during pregnancy, timing of prophylaxis and precautions to minimize
      risks.

PMID- 24683838
TI  - [Oncological intensive care: review of 2012 literature].
AB  - The objective of this paper is to review the literature published in 2012 in the
      field of intensive care and emergency related to oncology. Are discussed because
      of new original publications: prognosis, resuscitation techniques, oncologic
      emergencies, haemodynamic, respiratory and metabolic complications,
      microangiopathic anemia, serious toxicities of anticancer treatment and
      limitations to life-support techniques.

PMID- 24683839
TI  - [Henoch-Schonlein recurrent purpura: case report].
AB  - A 15-year old patient presented several episodes of uncontrollable vomiting with
      abdominal pain caused by a recurrent Henoch-Schonlein purpura. Renal impairment
      was demonstrated through the achievement of urinary test strips. Henoch-Schonlein
      purpura is the most common vasculitis in children. The clinical picture may
      include palpable purpura despite normal coagulation, arthralgia, abdominal pain
      and some degree of renal impairment. Most often, symptomatic treatment is
      effective. In some severe cases, corticosteroids are required. A control of
      hematuria and measure of blood pressure are recommended during the 6 to 12 months
      following the initial episode.

PMID- 24683840
TI  - [A case of chronic idiopathic purpura].
AB  - This paper focuses though on the medical management of the chronic ITP, as well
      as on the controversies generated by it and the therapeutic progress. Even if the
      idiopathic thrombocytopenic purpura is a rather frequent cause of childhood
      thrombocytopenia, it remains an exclusion diagnosis to be considered only in
      cases of persistent isolated thrombocytopenia observed in previously healthy
      children (other etiology excluded by the physical examination and medical
      history). Idiopathic thrombocytopenic purpura (ITP) is secondary to the premature
      platelet lysis by antibodies targeting the platelet membrane glycoproteins. The
      chronic evolution is defined by a prolongation of symptoms for more than 12
      months. The management of chronic ITP remains controversial. Novel treatments are
      on the spot, such as the rituximab and the thrombopoetin receptors' agonists (the
      most up-to-date therapies). We present the case of a 10 years old girl admitted
      in our department for recurrent diffuse purpuric lesions in the context of a
      chronic idiopathic purpura. The clinical aspects were classical: diffuse purpuric
      rash, without any other symptoms. An extended check-up was performed: it
      confirmed the presence of anti-platelets antibodies.

PMID- 24683841
TI  - [Diastematomyelia diagnosed prenatally].
AB  - We report a case of a 32-week-old foetus affected by diastematomyelia. A third
      trimester echography suggested a spine abnormality. Further investigations by CT
      scanner and MRI were performed to precise the anomaly and to better counsel the
      couple on the prognosis. We performed a review of the literature about
      embryological hypotheses, clinical presentations, antenatal investigations and
      prognosis of such a rare spinal malformation.

PMID- 24683842
TI  - [The walk of the skeptic].

PMID- 24683843
TI  - [Electrocardiography in the assessment of syncope: an example of bifascicular
      block becoming complete paroxystic block].

PMID- 24683844
TI  - [Being a freshman in the year 1945].
AB  - In 1945, the freshman was the witness of historical events such as the reception
      at the University of General de Gaulle, Sir W. Churchill and Sir A. Fleming.
      Other important events occured in that year: the end of the war in Europe, the
      revelation to the world of the nazi horours and the atomic bombing of Hiroshima.
      An extension of the principle of free thinking of facts and ideas appeared as a
      consequence of nazi occupation. The time was hard for the freshman concerning his
      studies and subsistance but the year 1945 was fascinating and came to an end with
      the revival, after seven years, of the grand student's feast of Saint-Verhaegen.

PMID- 24683845
TI  - [Fourteenth annual meeting of complications and emergencies of cancer patients].

PMID- 24683846
TI  - [2014, year of nursing research?].

PMID- 24683847
TI  - [Better control of induced pain].

PMID- 24683848
TI  - [Men-women inequalities in health].

PMID- 24683849
TI  - [Simplifying indicators for improving the quality and safety of nursing care].

PMID- 24683850
TI  - [Team work for managing obese persons].

PMID- 24683851
TI  - [Students, become involved in your training!].

PMID- 24683852
TI  - [Educational and preventive care implemented by student nurses].
AB  - The nursing training reference framework comprises 5 teaching units relating to
      the acquisition of skill 5: initiating and implementing educational and
      preventive care. The portion of teaching linked to the educational dimension of
      care corresponds to an evolution of healthcare needs, notably with people
      suffering from chronic diseases. The implementation of this reform of nursing
      studies can lead trainers to involve students more in educational projects for
      patients.

PMID- 24683853
TI  - [The role of tutor, a new nursing speciality?].
AB  - The implementation of the 2009 training reference framework reinforces the place
      of the tutor and formalises and defines their role. The analysis of the practice
      of tutor nurses reveals the emergence of a new professional group. However, while
      tutors are recognised for their expertise, they do not have sufficient time to
      supervise students and carry out assessments.

PMID- 24683854
TI  - [A technique requiring rigorous training].

PMID- 24683855
TI  - [Indications of negative pressure therapy].
AB  - Negative pressure therapy enables significant progress to be made in wound
      treatment by favouring tissue development.The indications depend on the shape of
      the wound and the exposed tissues. Specific training, as well as the respect of
      the recommendations set out bythe French National Authorityfor Health, help to
      favour cicatrisation and limit complications.

PMID- 24683856
TI  - [The choice of interface in negative pressure treatments].
AB  - The treatment of wounds by negative pressure requires the use of a foam or gauze
      interface. The study of scientific articles on the subject shows that the quality
      of the formation of granulation tissue and the pain during dressing removal
      differ depending on the technique, in favour of the use of the compress. On the
      other hand, no difference is found in terms of drainage capacity or the intensity
      of vascularisation.

PMID- 24683857
TI  - [Negative pressure treatment devices].
AB  - Negative pressure therapy systems comprise several types of devices and
      dressings. Some are specific to particular clinical situations.

PMID- 24683858
TI  - [Negative pressure therapy and acute wounds].
AB  - Negative pressure therapy medical techniques constitute a revolution in wound
      care, notably with acute wounds.The latter, often surgical, are treated as an
      emergency

PMID- 24683859
TI  - [Negative pressure therapy in traumatology].
AB  - The treatment of complex wounds in traumatology is a source of concern for
      nurses. Negative pressure therapy constitutes a solution for difficult-to-treat
      situations in the framework of open fractures and loss of limb tissue.

PMID- 24683860
TI  - [Negative pressure therapy in the loss of perineal substance].
AB  - Over the last ten years, negative pressure therapy has played a major role in the
      treatment of complex perineum wounds resulting from infection, trauma or
      cancer.The use of instillation has enabled its use to be extended to certain
      particularly difficult situations. It is also used routinely in support of
      dressing techniques for less complex wounds.

PMID- 24683861
TI  - [Treatment of pubic osteomyelitis secondary to pressure sores].
AB  - There is no consensus regarding the diagnostic and therapeutic strategy for pubic
      osteomyelitis secondary to pelvic pressure sores. Diagnosis is often difficult
      and bone biopsies with microbiological and anatomical-pathological examination
      remain the gold standard. The rate of cicatrisation of pressure sores is low.
      Cleansing and negative pressure treatment are key elements of the treatment.
      Optimising the care management with medical-surgical collaboration is being
      studied in the Ostear protocol.

PMID- 24683862
TI  - [Negative pressure therapy in the treatment of leg ulcers].
AB  - Leg ulcers are a common pathology. Negative pressure therapy is a second-line
      treatment which favours granulation and which must be followed by a graft.The
      main pitfall is the recurrence of ulcers.Whatever the cicatriasation technique,
      it is essential to consider the indications.

PMID- 24683863
TI  - [Incorrect use and complications of negative pressure therapy].
AB  - The specific training of teams as recommended by the French National Authority
      for Health in its document drawn up in January 2011 relating to the use of
      negative pressure therapy (NPT) is unfortunately rarely effective. The
      recognition of expertise in wounds and cicatrisation, the constitution of a
      multidisciplinary network as well as the use of information and communication
      technologies in the field of healthcare can provide nurses with the teaching and
      supervision required to master this technique.

PMID- 24683864
TI  - [Negative pressure therapy, do recommendations need updating?].

PMID- 24683865
TI  - [Instituting negative pressure therapy in the hospital].

PMID- 24683866
TI  - [Negative pressure therapy in the treatment of wounds. Bibliography].

PMID- 24683867
TI  - [Setting up situated learning in vascular rehabilitation].
AB  - A pedagogical tool as well as a concept, situated learning describes the skills
      used in a situation in a given context, structuring the reflection, analysis and
      choice of nursing procedures, based on theoretical knowledge, know-how and
      interpersonal skills. A vascular rehabilitation team has chosen to formalise two
      situations from among the most common care procedures carried out in the
      department: the changing of complex dressings and ensuring the personal hygiene
      and comfort of a dependent patient with skin wounds.

PMID- 24683868
TI  - [Computerized e-health, quality of nursing care].

PMID- 24683869
TI  - [The Patient Rights Act (PatRG)--Part 3: Burden of proof in liability questions
      and critical resume].
AB  - The article deals with the new regulations in the German Civil Code (Burgerliches
      Gesetzbuch - BGB), which came into effect in Germany as the Patient Rights Act
      (PatRG) on the 2/26/2013. In the third part, the burden of proof in liability
      questions (and 630h BGB) are discussed and critically analysed. In the discussion
      and a final resume points of criticism of the new law are pointed out.

PMID- 24683870
TI  - [Recreational boating accidents--Part 1: Catamnestic study].
AB  - Deaths on the water are common in the autopsy material of medicolegal institutes
      situated on the coast or big rivers and lakes (illustrated by the example of the
      Institute of Legal Medicine of Greifswald University). They mostly occur during
      recreational boating activities. Apart from hydro-meteorological influences,
      human error is the main cause of accidents. Often it is not sufficiently kept in
      mind whether the boat crew is fit for sailing and proper seamanship is ensured.
      Drowning (following initial hypothermia) is the most frequent cause of death.
      Medicolegal aspects are not decisive for ordering a forensic autopsy. As
      statistics are not compiled in a uniform way, a comparison of the data of
      different institutions engaged in investigating deaths at sea and during water
      sports activities is hardly possible, neither on a national nor an international
      basis--and the reconstruction of aquatic accidents is generally difficult. Fatal
      accidents can only be prevented by completely clarifying their causes.

PMID- 24683871
TI  - [Truth curves on soot blackened paper--apparatus-supported lie detection in Graz
      in the 1920s].
AB  - In the 1920s, experiments with apparatus-supported lie detection and registration
      of expression were conducted at the Criminological Institute of the University of
      Graz in order to establish a sound methodological basis for testimony research.
      For this purpose, the criminologist Ernst Seelig used a method of lie detection
      developed by the psychologist Vittorio Benussi, which focuses on the analysis of
      breathing. Benussi had stated that the expiration after telling a lie was faster
      than after telling the truth, but Seelig could not verify this rule in forensic
      practice. Consequently, this method of lie detection was of no practical use for
      criminology. Seelig also carried out experiments with the method of registration
      of expression developed by the psychiatrist Otto Lowenstein. He registered the
      examinee's thoracic and abdominal breathing and the movements of the extremities
      with the help of a kymograph. By interpretation of the curves recorded on soot
      blackened paper, conclusions concerning the mental elements of an offence as well
      as the existence of certain dispositions and of amnesia should have been made
      possible. Seelig was convinced of the efficiency of this method. These
      experiments can be regarded as early attempts at finding not only simple facts
      but also answers to quasi-metaphysical questions concerning the "true nature" of
      man with the help of methods based on natural science and modern technology. Thus
      they are precursors of present-day neuroscience and neuro-imaging.

PMID- 24683872
TI  - [Photodocumentation during autopsy].
AB  - Photography during autopsy is an important part of forensic imaging and essential
      for the documentation of autopsy findings. A forensic photograph mainly serves
      the purpose of providing evidence and should be authentic. But aesthetic artwork
      may improve both the attractiveness and acceptance of autopsies and thus help to
      increase the autopsy rate. Different materials were compared to each other as
      photographic backdrop, particularly with regard to reflection and contrast,
      stability of exposure measurement and monitoring of colour fidelity. The
      photofoil 9010 Dove Grey proved to be a material of outstanding quality. In
      practical application, the foil was scratch-resistant and easy to clean.
      Furthermore, backdrop boards with a gap, e.g. for head and neck, allow special
      perspectives without a distracting background.

PMID- 24683873
TI  - What is our 'duty of care'?

PMID- 24683874
TI  - Attitudes to mental health 'stuck in the dark ages', says Clegg.

PMID- 24683875
TI  - Small foetal size 'linked to poor heart health'.

PMID- 24683876
TI  - UK single parent rate 'fourth highest in Europe'.

PMID- 24683877
TI  - Scottish community nurses get tech savvy.

PMID- 24683878
TI  - Parents 'concerned' over children's sugar and fat intake.

PMID- 24683879
TI  - #adaywithdave: Ellie Moreton.

PMID- 24683880
TI  - Overcoming obesity: changing hearts and minds.

PMID- 24683881
TI  - The highs and lows of the student health visitor journey.

PMID- 24683882
TI  - An audit of new asthma guidance for school staff.
AB  - Asthma guidance for schools was created following an audit of all Shropshire and
      Telford schools in 2006. The guidance was introduced into Shropshire schools in
      2009 with the intention of helping to improve the confidence of school staff to
      manage acute and chronic asthma, thus improving children's attendance and health
      in school. The guidance was launched by the school nursing team through cluster
      head meetings with school nurses providing ongoing staff training and school
      staff support. After a successful launch and initial roll-out of the guidance a
      further audit was undertaken by the school nursing team in 2012. The audit tool
      was designed to measure the concordance with policy standards and provide insight
      into the uptake of the recommendations of the guidance. The tool gathered
      qualitative information from the parents to assess their level of confidence with
      the school's ability to manage their child's asthma. The results show the asthma
      guidance has improved school staff members' knowledge of asthma, and their
      confidence to manage a child's acute asthma attack.

PMID- 24683883
TI  - A survey of men's views on weight management.
AB  - Obesity is the state of imbalance between calories ingested and calories
      expended, which results in the accumulation of excessive or abnormal fat. Obesity
      stems from a number of different causes, which are often associated with other
      diseases, such as hypertension, diabetes and cancers. The article is based on the
      views of Northumberland men regarding weight management, and their knowledge of
      healthy eating. A survey was conducted of men in a workplace setting and 42%
      (n=84) of male employees responded. The survey results suggest that men were less
      likely to seek help from health professionals regarding weight management than
      other sources. This study also indicates that men are motivated to lose weight if
      they need to, and that interventions should be focused on good health and a
      reduction in weight. The results suggest that family and internet-based
      interventions have a significant part to play in helping men to address obesity.

PMID- 24683884
TI  - The integrated two-year check: a model of partnership working.
AB  - The Healthy Child Programme, the national universal public health programme for
      all children and families in the UK, requires health visitors to carry out a
      health review for children between two and 2.5 years. Similarly, the revised
      Early Years Foundation Stage statutory framework now places a new requirement on
      early years practitioners to review a child's learning and development through a
      progress check at two years. While work is being undertaken nationally for the
      two-year health review to be delivered jointly by health, early years and early
      intervention services, this paper discusses the development of an innovative,
      integrated local model that not only ensures better reach of two-year-old
      children in Harrow but also ensures best use of professional resources and
      expertise, and a more joined-up service for children and families.

PMID- 24683885
TI  - Delivering a health visiting leadership programme.

PMID- 24683886
TI  - Supporting smokers to quit for good.

PMID- 24683887
TI  - Connect with your clients and show you care.

PMID- 24683888
TI  - Recognising retinoblastoma: what health visitors need to know.
AB  - Retinoblastoma is very rare, with between 40 and 50 cases in the UK each year.
      However, delays in diagnosis and treatment can lead to loss of vision or even
      death, while with prompt treatment the outcome is much more positive. This
      article aims to provide community practitioners with the correct information
      about retinoblastoma, ensuring that babies and young children with retinoblastoma
      are identified at the first sign of the disease and are referred promptly. The
      article will examine the signs and symptoms of retinoblastoma, consider treatment
      options, present a case study and explore the role of the health visitor.

PMID- 24683889
TI  - [The neutrality of the medical expert].

PMID- 24683890
TI  - [The professional medical opinion: structure, content, statement (II). Part 2 of
      the article series: accidental bodily injury: principles of assessment].

PMID- 24683891
TI  - [Implementation of the AWMF guideline for the assessment of mental disorders].
AB  - The assessment of mental health for sick pay and disability supplementary
      insurance (BUZ) has, in comparison to specialties like internal medicine or
      orthopaedic surgery, a traditionally low selectivity between BU/AF (sick pay) or
      BU/Non-BU (BUZ). Reliability, validity and objectivity were low. The appraisals
      were created individually according to the designee's experience and were very
      inhomogeneous in structure and quality. The publication of the guideline 051-029
      in March 2012 provides improved grounds for the assessment of patients. In this
      article, we describe our experiences for the first twelve months after the
      implementation of the guideline.

PMID- 24683892
TI  - [The assessment of posttraumatic stress disorder in the transformation of DSM-IV
      TR DSM-5: what remains, what will change? (II)].

PMID- 24683893
TI  - [Ruptures of extensor tendons after open reduction and internal plate fixation of
      distal radius fractures].
AB  - Ruptures of extensor tendons after open reduction and internal plate fixation of
      distal radius fractures are a rare (up to 5%) and avoidable complication. The
      analysis of postoperative X-rays permits reliable detection of technical
      mistakes.

PMID- 24683894
TI  - [Development and consequences of physician shortages in Bavaria].
AB  - AIM: Germany's growing shortage of doctors is a current topic of numerous
      discussions in healthcare policy. The objective of this study is to show the
      medical supply situation and migratory movement of doctors in the outpatient and
      inpatient physician care sector, with particular emphasis on the immigration of
      foreign doctors to Germany and its consequences. SUBJECTS AND METHODS: The annual
      statistical reports from the Bavarian Medical Association and the Federal Medical
      Association were investigated with regard to foreign doctors and migratory
      movements. To establish Bavaria's situation regarding outpatient physician care,
      unpublished case reports and planning sheets of the Statutory Health Insurance
      Physicians in Bavaria (KVB) were analysed. A survey amongst Bavarian hospitals
      shows the current situation of the inpatient care sector. RESULTS: The trend of
      emigration by German doctors continues unabated, especially to Switzerland, UK,
      USA and Austria. In Bavaria, outpatient care by GPs or specialists is still
      standard or in oversupply. However, the survey was able to confirm a considerable
      lack of doctors for inpatient care. So far, it has been possible to compensate
      existing staff shortages in hospitals by employing foreign doctors, despite
      significant language deficits. DISCUSSION AND CONCLUSIONS: To resolve the
      shortage of doctors in future, a reform of the Medical Requirements Planning in
      combination with structural improvements and measures to integrate immigrant
      doctors is essential.

PMID- 24683895
TI  - [Requirements of the Federal Supreme Court on the prospects of success of an
      alternative method of treatment].

PMID- 24683896
TI  - [Treatment of metastatic rectal cancer in a clinic for Biological Medicine].

PMID- 24683897
TI  - [Continuing tension in Section O of the GOA].

PMID- 24683898
TI  - [Fundamentals of pain management].

PMID- 24683899
TI  - [The future of private health insurance].

PMID- 24683900
TI  - [Companion diagnostics - the future of modern medicine?].

PMID- 24683901
TI  - [Neuroradiological diagnosis of multiple sclerosis and epilepsy].

PMID- 24683902
TI  - [Bariatric surgery in adolescents?].

PMID- 24683903
TI  - [Orthopaedics and Traumatology: More than cutting, hammering and drilling].

PMID- 24683904
TI  - [Too many operations for back pain].

PMID- 24683905
TI  - [New treatment approaches in stroke].

PMID- 24683906
TI  - [Modern cancer treatment by active immunotherapy].

PMID- 24683907
TI  - [Micro Needling - a new therapeutic concept for scars].

PMID- 24683908
TI  - [Children with organ malformations grow up -- a challenge to the further
      treatment].

PMID- 24683909
TI  - [Assessment of objectively difficult ailments and illnesses].

PMID- 24683911
TI  - [Nerve stimulation for chronic headache].

PMID- 24683910
TI  - [Combat hypertension, avoid sequelae].

PMID- 24683912
TI  - [No all-clear for addictions -- new addictive drugs on the rise].

PMID- 24683913
TI  - Submission success rates.

PMID- 24683914
TI  - Peri-implantitis diagnosis and treatment by New Zealand periodontists and oral
      maxillofacial surgeons.
AB  - OBJECTIVES: This study aimed to investigate the understanding, diagnosis and
      management of peri-implantitis by New Zealand periodontists and oral
      maxillofacial surgeons (OMFS). DESIGN: Telephone interviews (in combination with
      a postal and electronic survey) were conducted of all 25 periodontists and 32
      OMFS listed as specialists on the New Zealand Dental Register. A seven item multi
      choice and short answer questionnaire was used to investigate: their definition
      of peri-implantitis; the number of annual referrals received in their practice
      for this condition; their diagnostic, preventive and treatment strategies for
      peri-implantitis; and their perception of the role of general dental
      practitioners in its management. RESULTS: The participation rate was 84.6%. Most
      respondents defined peri-implantitis as a disease of multifactorial aetiology
      that leads to destruction of the bone supporting an implant. The average number
      of cases seen annually differed between periodontists (11 cases/year) and OMFS (4
      cases/year). The criteria used by the respondents to diagnose peri-implantitis
      included increased probing depths and radiographic evidence of bone loss. Each
      type of specialist used mechanical debridement for treatment, but a higher
      proportion of OMFS performed surgical procedures as treatment. The prevention
      strategies used smoking cessation advice and ensuring good plaque control. All
      respondents agreed that peri-implantitis is an important disease that can lead to
      implant failure, and all acknowledged the role of general dental practitioners in
      diagnosis, referral for treatment and long-term implant maintenance. CONCLUSION:
      The definition, diagnostic criteria and management strategies used by New Zealand
      specialists are generally consistent with those found in the literature. No
      evidence-based, gold standard treatment protocol for peri-implantitis has been
      identified in the literature, and New Zealand specialists use a range of
      treatment modalities.

PMID- 24683915
TI  - Acceptability of the Hall Technique to parents and children.
AB  - OBJECTIVE: To investigate the acceptability of stainless steel crowns placed by
      dental therapists on children's primary molars using the Hall Technique. DESIGN:
      Mixed methods approach, using qualitative inductive analysis and quantitative
      analysis. SETTING: Hawke's Bay Community Oral Health Service METHODS: One focus
      group was conducted and ten thirty-minute phone interviews were undertaken with
      parents of children who had previously had a stainless steel crown placed using
      the Hall Technique (over the period 1 December 2011 to 31 May 2012). An inductive
      approach was used to analyse the qualitative research data, and the information
      was arranged into several categories based on the key themes which arose.
      Children treated with the Hall Technique were asked immediately after treatment
      whether they had enjoyed their visit to the clinic that day. RESULTS: Common
      themes were found with regard to appearance, pain, the procedure, and general
      opinions on acceptability. Nearly all (90%) of the children responded positively
      about their visit to the clinic. CONCLUSION: There was a high degree of
      acceptance among both parents and children for stainless steel crown placement
      using the Hall Technique in this group.

PMID- 24683916
TI  - Ukaipo niho: the place of nurturing for oral health.
AB  - OBJECTIVES: To report on oral-health-related characteristics, beliefs, and
      behaviours among participants in a randomised control trial of an intervention to
      prevent early childhood caries (ECC) among Maori children, and to determine
      whether there were any systematic differences between the intervention and
      control groups at baseline. DESIGN: Baseline measurements from a randomised
      control trial (involving 222 pregnant Maori women allocated randomly to either
      Intervention or Delayed groups) which is currently underway. SETTING: The rohe
      (tribal area) of Waikato-Tainui. METHODS: Self-report information collected on
      sociodemographic characteristics, pregnancy details, self-reported general and
      oral health and health-related behaviours, and oral health beliefs. RESULTS:
      Other than those in the Delayed group being slightly older, on average, there
      were no significant differences between the two groups. Some 37.0% were expecting
      their first child. Most reported good health; 43.6% were current smokers, and
      26.4% had never smoked. Only 8.2% were current users of alcohol. Almost all were
      dentate, and 57.7% described their oral health as fair or poor. One in six had
      had toothache in the previous year; 33.8% reported being uncomfortable about the
      appearance of their teeth, and 27.7% reported difficulty in eating. Dental
      service-use was relatively low and symptom-related; 78.9% needed to see a
      dentist. Overall, most of the sample believed that it was important to avoid
      sweet foods, visit dentists and to brush the teeth, while about half thought that
      using fluoride toothpaste and using floss were important. Some 38.2% felt that
      drinking fluoridated water was important. Oral-health-related fatalism was
      apparent, with 74.2% believing that most people usually get dental problems,
      58.6% believing that most people will need extractions at some stage, and that
      most children eventually get dental caries. CONCLUSIONS: Mothers' important role
      in nurturing the well-being of the young child includes the protection and
      maintenance of the growing child's oral health (or ukaipo niho). The findings
      provide important insights into Maori mothers' oral health knowledge, beliefs and
      practices.

PMID- 24683917
TI  - The potential for losing community water fluoridation.

PMID- 24683918
TI  - Dr. Litras responds.

PMID- 24683919
TI  - Re: Misinformation of fluoridation.

PMID- 24683921
TI  - Changing times.

PMID- 24683920
TI  - Dr. Litras responds.

PMID- 24683922
TI  - Helping all members succeed.

PMID- 24683923
TI  - Training the dragon.

PMID- 24683924
TI  - Tooth number, World War II, nuns, and the real fountain of youth.
AB  - A new appreciation for the direct relationship of mouth health to systemic health
      is forcing re-evaluation of previous concepts of oral health strategies. Although
      a person shows adaptation to loss of some permanent teeth, it appears a threshold
      of 10 functional pairs or 20 teeth have linkage to a number of disabling diseases
      of aging. The Shortened Dental Arch concept has limitations for sustainability
      and leaves little functional cushion. Nevertheless, when teeth are lost leaving
      fewer than 20, systemic disease and mortality risk increase significantly.
      Several theories try to explain the phenomenon. An unusually credible study,
      however, changes the metric to fewer teeth, nine or less, before a cognitive
      decline is noted. Due to a standardized high level of prosthodontic treatment in
      that study, some of the deleterious health effects of tooth loss appear to be
      mitigated. The importance of these findings has implications for tooth
      replacement strategies. Recognizing the huge biologic and psychological cost of
      tooth loss, a renewed emphasis to maintain natural teeth is indicated. When fewer
      than 20 teeth are viable, well-made prosthodontics, including maxillary complete
      denture or a mandibular partial or overdenture, both tooth- and implant
      supported, could be remunerative therapies.

PMID- 24683925
TI  - Role of the dentist in prevention and treatment of oral complications secondary
      to cancer treatment.

PMID- 24683926
TI  - Tax savings with the hybrid retirement plan of the future--cash balance plans.

PMID- 24683927
TI  - What's your resolution?

PMID- 24683928
TI  - Unintended consequence.

PMID- 24683929
TI  - Hope--tempered with vision and action.

PMID- 24683930
TI  - Effect of the Breast and Ccervical Cancer Ttreatment Act on access to screening
      and treatment in Oklahoma.
AB  - The purpose of this study was to explore the impact of Medicaid on changes in
      coverage among women with newly diagnosed breast cancers, in the first years of
      program implementation. Women and their providers used the program, with nearly
      double the number of women covered by Medicaid in the three years after
      implementation. The treatment program, as implemented in Oklahoma, reached the
      target population and provided coverage to women who previously had none. The
      study found a promising, though nonsignificant, reduction in the time between
      diagnosis and treatment among women diagnosed with breast cancer when Medicaid
      was their primary payer.

PMID- 24683931
TI  - Fever notions of the misinformed: a quality improvement project.
AB  - Tracking temperatures graphically, recognizing their normal quotidian variations,
      and acknowledging that fever may be a beneficial physiological response to
      infection, have been lost in modern hospital care. Further, injudicious use of
      antibiotics for "low-grade fever" contributes to the multiple drug resistant
      organism and Clostridium difficile epidemics. This essay discusses these issues
      and proposes changing common misperceptions of fever as a quality improvement
      project.

PMID- 24683932
TI  - An Oklahoma approach to healthcare improvement: leveraging technology and
      innovative partnerships to reduce costs and improve care quality.

PMID- 24683933
TI  - The world is in our hands.

PMID- 24683934
TI  - Health and housing outcomes from green renovation of low-income housing in
      Washington, DC.
AB  - Green building systems have proliferated recently, but studies are limited of
      associated health and housing outcomes. The authors measured self-reported
      resident physical and mental health, allergens, and building conditions at
      baseline and one-year follow-up in a low-income housing development being
      renovated in accordance with green healthy housing improvements (Enterprise Green
      Communities standards and Leadership in Energy & Environmental Design [LEED] gold
      certification). Self-reported general health in adults significantly improved
      from 59% to 67% (p = .026), with large statistically significant improvements in
      water/ dampness problems, cockroaches and rodents, and reduced pesticide use.
      Median cockroach (Bla g1) and mouse (Mus m1) allergen dust loadings showed large
      and statistically significant reductions from baseline to three months
      postintervention and were sustained at one year (both p < .05). Energy and water
      cost savings were 16% and 54%, respectively. Incorporating Enterprise Green
      Communities and LEED standards in low-income housing renovation improves health
      and housing conditions and can help to reduce disparities. All green housing
      standards should include health-related requirements.

PMID- 24683935
TI  - Preventing diseases and outbreaks at child care centers using an education,
      evaluation, and inspection method.
AB  - From 2005 to 2008, Washoe County, Nevada, child care centers experienced an
      increase in illnesses from communicable disease outbreaks. The number of ill
      children and caregivers from these outbreaks went from 26 in 2005 to 266 in 2008,
      an increase of 923%. A clear need to reverse this trend existed. Therefore, in
      2009 Washoe County strengthened its regulations for child care facilities by
      adding numerous communicable disease prevention standards. In addition, in 2009 a
      two-year education, evaluation, and inspection program was implemented at Washoe
      County child care centers. Following the implementation of this program, a
      decline occurred in the number of illnesses. The number of ill children and
      caregivers from outbreaks went from 266 in 2008 to 13 in 2011, a decrease of 95%.

PMID- 24683936
TI  - Regulations, policies, and guidelines addressing environmental exposures in early
      learning environments: a review.
AB  - Infants and young children under five years of age are uniquely vulnerable to
      certain environmental contaminants. Some of these contaminants have been found in
      early learning environments (ELEs), or child care and family child care settings
      where children spend an average of 40 hours a week. These contaminants as well as
      infants' and children's unique physiology, exposures, and behaviors in child care
      settings are the focus of this article. Current child care and family child care
      licensing requirements specific to environmental health-related issues are also
      reviewed. Data were reviewed and analyzed from the following surveys: the 2008
      Child Care Licensing Survey, the First National Environmental Health Survey of
      Child Care Centers, and the Children's Total Exposure to Persistent Pesticides
      and Other Persistent Organic Pollutants. The authors' analysis suggests that
      current state licensing programs impose only the most basic environmental health
      protection requirements. No mandatory federal regulations standardize child care
      and family child care regulatory efforts nationally. Resources are available,
      however, from federal agencies and other children's environmental health
      organizations that may provide guidance for how to establish better environmental
      health protection measures in ELEs.

PMID- 24683937
TI  - Breathe easy at home: a web-based referral system linking clinical sites with
      housing code enforcement for patients with asthma.
AB  - Asthma, the most significant cause of pediatric morbidity and mortality, is
      exacerbated by adverse environmental conditions, especially substandard housing.
      The clinical care provider is often unable to address housing and environmental
      trigger issues. In Boston, Massachusetts, a web-based referral system called
      Breathe Easy At Home has been put in place, through which clinicians can refer
      patients to have their homes inspected for housing code violations that may be
      contributing to their asthma. Violations will then be brought to the attention of
      the landlord, who then has the option of redressing the issue or be taken to
      housing court. By bringing the local public health department, the city's
      inspectional services department, and the clinical care provider together with
      the help of a program coordinator, Breathe Easy At Home is able to provide
      comprehensive care to asthma patients. This program also serves as a replicable
      model for other cities and jurisdictions to follow.

PMID- 24683938
TI  - National Environmental Health Science and Protection Accreditation Council
      degrees can lead to U.S. Public Health Service commissions through accredited
      coursework and internships.

PMID- 24683939
TI  - Food safety tools and products for environmental health practitioners.

PMID- 24683940
TI  - CDC's environmental public health tracking network: an innovative dynamic
      surveillance system for you.

PMID- 24683941
TI  - Thirty-three dramatic predictions for 2030.

PMID- 24683942
TI  - State health agency workforce shortages.

PMID- 24683943
TI  - The keys to building environmental health capacity: advancements in IT and
      innovation.

PMID- 24683944
TI  - The testis: developmental, anatomic, and functional considerations.

PMID- 24683945
TI  - Embryology and physiology of testicular development and descent.
AB  - Sexual differentiation starts with the development of bipotential gonads that
      further differentiate into testes or ovaries. The fetal testis secretes hormones
      that guide the differentiation of internal and external sex organs, whereas the
      fetal ovary remains rather inactive hormonally. Defects in gonadal
      differentiation or hormone secretion and action result in disorders of sex
      development (DSD). Testicular descent is a continuum that has often been
      described to occur in two main phases: the transabdominal phase and the
      inguinoscrotal phase. The first phase is according to animal studies dependent on
      Leydig cell-derived insulin-like peptide 3 (INSL3) that induces male-like
      development of the gubernaculum. This phase is rarely disrupted in man. The
      inguinoscrotal phase is dependent on androgens, also secreted by Leydig cells.

PMID- 24683946
TI  - Diagnosis and evaluation of hypogonadism.
AB  - Hypogonadism is defined as defects in gonadal response to gonadotropins or sex
      hormone biosynthesis. Clinical evaluation and diagnosis of patients is
      challenging, particularly before puberty. Basal determinations of the
      gonadotropins luteinizing hormone, follicle-stimulating hormone, the gonadal sex
      steroids testosterone and/or estrogen and markers of gonadal function including
      inhibin B and anti-Mullerian hormone are useful, but only at specific ages, thus
      necessitating combined hormonal tests with meticulous physical examination. GnRH
      testing can be useful, and may be used in combination with hCG testing to
      discriminate between isolated hypogonadotropic hypogonadism and constitutional
      delay of growth and puberty. Urine steroid profiles may be helpful in the
      diagnosis of androgen biosynthetic defects. Also increasingly important is
      genotypic screening for genetic or chromosomal abnormalities, together with
      detailed family and medical histories including antecedent substance abuse,
      chronic disease, and exposure to chemotherapy or radiotherapy. This chapter
      explores the diagnosis and evaluation of patients with hypogonadism and reviews
      the genetic/chromosomal factors involved in the condition.

PMID- 24683947
TI  - Treatment of hypogonadism in males.
AB  - The treatment of adolescent males with hypogonadism using testosterone is
      dependent on the underlying diagnosis as well as the patient's and family's
      preferences. Those with testicular failure, always a pathologic condition, begin
      lifelong therapy, while short-term therapy is often begun for those who have a
      delayed puberty. There is a wide variety of testosterone formulations available,
      with differences in adverse events sometimes associated with the method of
      administration. The goals of treatment involve stimulating physical puberty,
      including achievement of virilization, a normal muscle mass and bone mineral
      density for age, and improvement in psychosocial wellbeing. While androgen
      therapy results in physical changes of puberty, the potential for fertility must
      be considered for those with permanent gonadotropin deficiency. in this
      population, therapy with gonadotropins or gonadotropin releasing hormone may be
      effective. For those with testicular failure, fertility may be possible but
      requires assisted reproductive procedures.

PMID- 24683948
TI  - Cryptorchidism: a clinical perspective.
AB  - Incomplete descent of the testes is the most common genital anomaly in newborn
      boys. The prevalence varies with apparent geographical differences. The etiology
      of cryptorchidism is considered to be multifactorial (genetic, maternal, and
      environmental factors), and it occurs most often as an isolated disorder with no
      obvious cause. Cryptorchidism should not be left untreated, since there is an
      increased risk of developing testicular cancer and infertility/subfertility.
      However, the mode and timing of treatment, as well as the risks of subfertility
      and testicular cancer have long been controversial. There is increasing evidence
      that treatment should be performed early in life. Randomized volumetric and
      histological studies have shown that early treatment before the age of one year
      is beneficial for testicular development and future spermatogenesis compared to
      later treatment. It remains to be proven that this difference persists into
      adulthood. Due to the low efficacy rate and the possible adverse effects of
      hormonal treatment, surgery is preferred. The exact optimal time for orchidopexy
      is not known, but it should probably be before one year of age, at centers with
      expertise in pediatric anesthesiology and pediatric surgery/urology. The risk of
      testicular cancer is also reduced if orchidopexy is performed before puberty;
      however it remains to be proven if treatment in early infancy reduces the risk
      even further.

PMID- 24683949
TI  - Testicular germ cell tumors.
AB  - Human germ cell tumors are of interest because of their epidemiology, clinical
      behavior and pathobiology. Histologically, they are subdivided into various
      elements, with similarities to embryogenesis. Recent insights resulted in a
      division of five types of human germ cell tumors. In the context of male germ
      cells, three are relevant; Type I: teratomas and yolk sac tumors of neonates and
      infants; Type II: seminomas and nonseminomas of (predominantly) adolescents and
      adults; and Type III: spermatocytic seminomas of the elderly. Recent studies led
      to significant increases in understanding of the parameters involved in the
      earliest pathogenetic steps of human germ cells tumors, in particularly the
      seminomas and nonseminomas (Type II). In case of a disturbed gonadal physiology,
      either due to the germ cell itself, or the micro-environment, embryonic germ
      cells during a specific window of sensitization can be blocked in their
      maturation, resulting in carcinoma in situ or gonadoblastoma, the precursors of
      seminomas and nonseminomas. The level of testicularization of the gonad
      determines the histological composition of the precursor. These insights will
      allow better definition of individuals at risk to develop a germ cell malignancy,
      with putative preventive measurements, and allow better selection of scientific
      approaches to elucidate the pathogenesis.

PMID- 24683950
TI  - Macroorchidism in childhood and adolescence: an update.
AB  - In the last 30 years, scientific literature has been enriched with studies which
      demonstrate the importance of evaluating testis volume to recognize certain
      genetic and endocrine diseases. Macroorchidism is defined as an increase of
      testicular volume at least twice the norm for age. In clinical practice, when
      macroorchidism is suspected, the testicular volume may be evaluated with the
      Prader orchidometer and/or US, calculated by this formula: L x W x H x 0.71 and
      the resulting value should be compared with a table of percentiles for each age.
      Macroorchidism is a relatively uncommon sign; however, when present, it almost
      always has clinical relevance. Five groups of conditions are reviewed: genetic,
      endocrine, idiopathic and secondary to neoplasm or testicular torsions. An X
      linked mental retardation syndrome must be suspected in all patients with
      macrorchidism, phenotypic abnormalities, and mental retardation. Furthermore, it
      is important to identify other males affected in the same family to confirm the X
      linked transmission. In these cases, the patient must be referred to specialized
      cytogenetic centres for determination of fragile sites. Other possible etiologies
      of macroorchidism are long-standing primary hypothyroidism, adrenal remnants in
      congenital adrenal hyperplasia, follicle stimulating hormone (FSH)-secreting
      pituitary macroadenomas, local tumors, lymphomas, and aromatase deficiency. Early
      diagnosis is important in order to identify and reduce the incidence of X-linked
      mental retardation in affected families and to begin treatment in endocrinologic,
      tumoral and surgical disorders.

PMID- 24683951
TI  - Varicocele: a dilemma in adolescent males.
AB  - Varicoceles are the most common cause of infertility in men. Despite the high
      prevalence of varicoceles, only a small percentage of men with varicoceles have
      subfertility or infertility. In adolescents, the prevalence of varicoceles
      increases dramatically during puberty to reach adult prevalence rates. The
      development of varicoceles during puberty can impair testicular growth and
      function. Data on hormonal and semen parameters in adolescents with varicoceles
      are limited, making it harder to determine which varicoceles are associated with
      infertility and which may benefit from surgery. The main indications for
      varicocelectomy in adolescents with varicoceles include a volume differential
      between unaffected and affected testes or abnormality in semen analysis.

PMID- 24683952
TI  - Preface. Information processing in medical imaging.

PMID- 24683953
TI  - Matched signal detection on graphs: theory and application to brain network
      classification.
AB  - We develop a matched signal detection (MSD) theory for signals with an intrinsic
      structure described by a weighted graph. Hypothesis tests are formulated under
      different signal models. In the simplest scenario, we assume that the signal is
      deterministic with noise in a subspace spanned by a subset of eigenvectors of the
      graph Laplacian. The conventional matched subspace detection can be easily
      extended to this case. Furthermore, we study signals with certain level of
      smoothness. The test turns out to be a weighted energy detector, when the noise
      variance is negligible. More generally, we presume that the signal follows a
      prior distribution, which could be learnt from training data. The test statistic
      is then the difference of signal variations on associated graph structures, if an
      Ising model is adopted. Effectiveness of the MSD on graph is evaluated both by
      simulation and real data. We apply it to the network classification problem of
      Alzheimer's disease (AD) particularly. The preliminary results demonstrate that
      our approach is able to exploit the sub-manifold structure of the data, and
      therefore achieve a better performance than the traditional principle component
      analysis (PCA).

PMID- 24683954
TI  - Exploring high-order functional interactions via structurally-weighted LASSO
      models.
AB  - A major objective of brain science research is to model and quantify functional
      interaction patterns among neural networks, in the sense that meaningful
      interaction patterns reflect the working mechanisms of neural systems and
      represent their relationships with the external world. Most current research
      approaches in the neuroimaging field, however, focus on pair-wise
      functional/effective connectivity and are thus unable to handle high-order,
      network-scale functional interactions. In this paper, we propose a novel
      structurally-weighted LASSO (SW-LASSO) regression model to represent the
      functional interaction among multiple regions of interests (ROIs) based on
      resting state fMRI (rsfMRI) data. In particular, the structural connectivity
      constraints derived from diffusion tenor imaging (DTI) data are used to guide the
      selection of the weights, thus adaptively adjusting the penalty levels of
      different coefficients which correspond to different ROIs. The robustness and
      accuracy of our models are evaluated and demonstrated via a series of carefully
      designed experiments. In an application example, the generated regression graphs
      show different assortative mixing patterns between Mild Cognitive Impairment
      (MCI) patients and normal controls (NC). Our results indicate that the proposed
      model has promising potential to enable the construction of high-order functional
      networks and their applications in clinical datasets.

PMID- 24683955
TI  - Feature-based alignment of volumetric multi-modal images.
AB  - This paper proposes a method for aligning image volumes acquired from different
      imaging modalities (e.g. MR, CT) based on 3D scale-invariant image features. A
      novel method for encoding invariant feature geometry and appearance is developed,
      based on the assumption of locally linear intensity relationships, providing a
      solution to poor repeatability of feature detection in different image
      modalities. The encoding method is incorporated into a probabilistic feature
      based model for multi-modal image alignment. The model parameters are estimated
      via a group-wise alignment algorithm, that iteratively alternates between
      estimating a feature-based model from feature data, then realigning feature data
      to the model, converging to a stable alignment solution with few pre-processing
      or pre-alignment requirements. The resulting model can be used to align multi
      modal image data with the benefits of invariant feature correspondence: globally
      optimal solutions, high efficiency and low memory usage. The method is tested on
      the difficult RIRE data set of CT, T1, T2, PD and MP-RAGE brain images of
      subjects exhibiting significant inter-subject variability due to pathology.

PMID- 24683956
TI  - Bayesian estimation of regularization and atlas building in diffeomorphic image
      registration.
AB  - This paper presents a generative Bayesian model for diffeomorphic image
      registration and atlas building. We develop an atlas estimation procedure that
      simultaneously estimates the parameters controlling the smoothness of the
      diffeomorphic transformations. To achieve this, we introduce a Monte Carlo
      Expectation Maximization algorithm, where the expectation step is approximated
      via Hamiltonian Monte Carlo sampling on the manifold of diffeomorphisms. An added
      benefit of this stochastic approach is that it can successfully solve difficult
      registration problems involving large deformations, where direct geodesic
      optimization fails. Using synthetic data generated from the forward model with
      known parameters, we demonstrate the ability of our model to successfully recover
      the atlas and regularization parameters. We also demonstrate the effectiveness of
      the proposed method in the atlas estimation problem for 3D brain images.

PMID- 24683957
TI  - Gradient competition anisotropy for centerline extraction and segmentation of
      spinal cords.
AB  - Centerline extraction and segmentation of the spinal cord--an intensity varying
      and elliptical curvilinear structure under strong neighboring disturbance are
      extremely challenging. This study proposes the gradient competition anisotropy
      technique to perform spinal cord centerline extraction and segmentation. The
      contribution of the proposed method is threefold--1) The gradient competition
      descriptor compares the image gradient obtained at different detection scales to
      suppress neighboring disturbance. It reliably recognizes the curvilinearity and
      orientations of elliptical curvilinear objects. 2) The orientation coherence
      anisotropy analyzes the detection responses offered by the gradient competition
      descriptor. It enforces structure orientation consistency to sustain strong
      disturbance introduced by high contrast neighboring objects to perform centerline
      extraction. 3) The intensity coherence segmentation quantifies the intensity
      difference between the centerline and the voxels in the vicinity of the
      centerline. It effectively removes the object intensity variation along the
      structure to accurately delineate the target structure. They constitute the
      gradient competition anisotropy method which can robustly and accurately detect
      the centerline and boundary of the spinal cord. It is validated and compared
      using 25 clinical datasets. It is demonstrated that the proposed method well
      suits the applications of spinal cord centerline extraction and segmentation.

PMID- 24683958
TI  - Automated segmentation of the cerebellar lobules using boundary specific
      classification and evolution.
AB  - The cerebellum is instrumental in coordinating many vital functions ranging from
      speech and balance to eye movement. The effect of cerebellar pathology on these
      functions is frequently examined using volumetric studies that depend on
      consistent and accurate delineation, however, no existing automated methods
      adequately delineate the cerebellar lobules. In this work, we describe a method
      we call the Automatic Classification of Cerebellar Lobules Algorithm using
      Implicit Multi-boundary evolution (ACCLAIM). A multiple object geometric
      deformable model (MGDM) enables each boundary surface of each individual lobule
      to be evolved under different level set speeds. An important innovation described
      in this work is that the speed for each lobule boundary is derived from a
      classifier trained specifically to identify that boundary. We compared our method
      to segmentations obtained using the atlas-based and multi-atlas fusion
      techniques, and demonstrate ACCLAIM's superior performance.

PMID- 24683959
TI  - Tree-space statistics and approximations for large-scale analysis of anatomical
      trees.
AB  - Statistical analysis of anatomical trees is hard to perform due to differences in
      the topological structure of the trees. In this paper we define statistical
      properties of leaf-labeled anatomical trees with geometric edge attributes by
      considering the anatomical trees as points in the geometric space of leaf-labeled
      trees. This tree-space is a geodesic metric space where any two trees are
      connected by a unique shortest path, which corresponds to a tree deformation.
      However, tree-space is not a manifold, and the usual strategy of performing
      statistical analysis in a tangent space and projecting onto tree-space is not
      available. Using tree-space and its shortest paths, a variety of statistical
      properties, such as mean, principal component, hypothesis testing and linear
      discriminant analysis can be defined. For some of these properties it is still an
      open problem how to compute them; others (like the mean) can be computed, but
      efficient alternatives are helpful in speeding up algorithms that use means
      iteratively, like hypothesis testing. In this paper, we take advantage of a very
      large dataset (N = 8016) to obtain computable approximations, under the
      assumption that the data trees parametrize the relevant parts of tree-space well.
      Using the developed approximate statistics, we illustrate how the structure and
      geometry of airway trees vary across a population and show that airway trees with
      Chronic Obstructive Pulmonary Disease come from a different distribution in tree
      space than healthy ones. Software is available from
      http://image.diku.dk/aasa/software.php.

PMID- 24683960
TI  - Predicting cognitive data from medical images using sparse linear regression.
AB  - We present a new framework for predicting cognitive or other continuous-variable
      data from medical images. Current methods of probing the connection between
      medical images and other clinical data typically use voxel-based mass univariate
      approaches. These approaches do not take into account the multivariate, network
      based interactions between the various areas of the brain and do not give readily
      interpretable metrics that describe how strongly cognitive function is related to
      neuroanatomical structure. On the other hand, high-dimensional machine learning
      techniques do not typically provide a direct method for discovering which parts
      of the brain are used for making predictions. We present a framework, based on
      recent work in sparse linear regression, that addresses both drawbacks of mass
      univariate approaches, while preserving the direct spatial interpretability that
      they provide. In addition, we present a novel optimization algorithm that adapts
      the conjugate gradient method for sparse regression on medical imaging data. This
      algorithm produces coefficients that are more interpretable than existing sparse
      regression techniques.

PMID- 24683961
TI  - A multiple hypothesis based method for particle tracking and its extension for
      cell segmentation.
AB  - In biological studies, it is often required to track thousands of small particles
      in microscopic images to analyze underlying mechanisms of cellular and
      subcellular processes which may lead to better understanding of some disease
      processes. In this paper, we present an automatic particle tracking method and
      apply it for analyzing an essential subcellular process, namely clathrin mediated
      endocytosis using total internal reflection microscopy. Particles are detected by
      using image filters and subsequently Gaussian mixture models are fitted to
      achieve sub-pixel resolution. A multiple hypothesis based framework is designed
      to solve data association problems and handle splitting/merging events. The
      tracking method is demonstrated on synthetic data under different scenarios and
      applied to real data. We also show that, by equipping with a cell detection
      module, the method can be extended straightforwardly for segmenting cell images
      taken by two-photon excitation microscopy.

PMID- 24683962
TI  - A multiple model probability hypothesis density tracker for time-lapse cell
      microscopy sequences.
AB  - Quantitative analysis of the dynamics of tiny cellular and subcellular structures
      in time-lapse cell microscopy sequences requires the development of a reliable
      multi-target tracking method capable of tracking numerous similar targets in the
      presence of high levels of noise, high target density, maneuvering motion
      patterns and intricate interactions. The linear Gaussian jump Markov system
      probability hypothesis density (LGJMS-PHD) filter is a recent Bayesian tracking
      filter that is well-suited for this task. However, the existing recursion
      equations for this filter do not consider a state-dependent transition
      probability matrix. As required in many biological applications, we propose a new
      closed-form recursion that incorporates this assumption and introduce a general
      framework for particle tracking using the proposed filter. We apply our scheme to
      multi-target tracking in total internal reflection fluorescence microscopy
      (TIRFM) sequences and evaluate the performance of our filter against the existing
      LGJMS-PHD and IMM-JPDA filters.

PMID- 24683963
TI  - Multi-layer deformation estimation for fluoroscopic imaging.
AB  - Accurate estimation of motion in fluoroscopic imaging sequences is critical for
      improved frame interpolation/extrapolation, tracking of surgical instruments, and
      Digital Subtraction Angiography (DSA). The projection of multiple transparent
      objects undergoing multiple complicated deformations in 3D onto a single 2D view
      makes this motion estimation problem quite challenging and ill-suited to existing
      techniques used in medical image analysis. We propose a novel method for jointly
      decomposing the observed image into a set of additive layers each associated with
      its corresponding smooth nonlinear deformation, which together model the non
      smooth motion observed in the projection images across several frames. A total
      variation based regularization penalty is used to incorporate the known structure
      of the input frames for well posedness of the layer separation problem. We
      present the use of this model for frame interpolation and artifact reduction in
      DSA. Results are included from synthetic and real clinical datasets.

PMID- 24683964
TI  - Fiber connectivity integrated brain activation detection.
AB  - Inference of brain activation through the analysis of functional magnetic
      resonance imaging (fMRI) data is seriously confounded by the high level f noise
      in the observations. To mitigate the effects of noise, we propose incorporating
      anatomical connectivity into brain activation detection as motivated by how the
      functional integration of distinct brain areas is facilitated via neural fiber
      pathways. In this work, we formulate activation detection as a probabilistic
      graph-based segmentation problem with fiber networks estimated from diffusion MRI
      (dMRI) data serving as a prior. Our approach is reinforced with a data-driven
      scheme for refining the connectivity prior to reflect the fact that not all
      fibers are necessarily deployed during a given cognitive task as well as to
      account for false fiber tracts arising from limitations of dMRI tractography.
      Validating on real clinical data collected from 7 schizophrenia patients and 13
      matched healthy controls, we show that incorporating anatomical connectivity
      significantly increases sensitivity in detecting task activation in controls
      compared to existing univariate techniques. Further, we illustrate how our model
      enables the detection of significant group activation differences between
      controls and patients that are missed with standard methods.

PMID- 24683965
TI  - Diffeomorphic metric mapping of hybrid diffusion imaging based on BFOR signal
      basis.
AB  - In this paper, we propose a large deformation diffeomorphic metric mapping
      algorithm to align multiple b-value diffusion weighted imaging (mDWI) data,
      specifically acquired via hybrid diffusion imaging (HYDI), denoted as LDDMM-HYDI.
      We adopt the work given in Hosseinbor et al. (2012) and represent the q-space
      diffusion signal with the Bessel Fourier orientation reconstruction (BFOR) signal
      basis. The BFOR framework provides the representation of mDWI in the q-space and
      thus reduces memory requirement. In addition, since the BFOR signal basis is
      orthonormal, the L2 norm that quantifies the differences in q-space signals of
      any two mDWI datasets can be easily computed as the sum of the squared
      differences in the BFOR expansion coefficients. In this work, we show that the
      reorientation of the q-space signal due to spatial transformation can be easily
      defined on the BFOR signal basis. We incorporate the BFOR signal basis into the
      LDDMM framework and derive the gradient descent algorithm for LDDMM-HYDI with
      explicit orientation optimization. Using real HYDI datasets, we show that it is
      important to consider the variation of mDWI reorientation due to a small change
      in diffeomorphic transformation in the LDDMM-HYDI optimization.

PMID- 24683966
TI  - Hyperbolic harmonic brain surface registration with curvature-based landmark
      matching.
AB  - Brain Cortical surface registration is required for inter-subject studies of
      functional and anatomical data. Harmonic mapping has been applied for brain
      mapping, due to its existence, uniqueness, regularity and numerical stability. In
      order to improve the registration accuracy, sculcal landmarks are usually used as
      constraints for brain registration. Unfortunately, constrained harmonic mappings
      may not be diffeomorphic and produces invalid registration. This work conquer
      this problem by changing the Riemannian metric on the target cortical surface o a
      hyperbolic metric, so that the harmonic mapping is guaranteed to be a
      diffeomorphism while the landmark constraints are enforced as boundary matching
      condition. The computational algorithms are based on the Ricci flow method and
      yperbolic heat diffusion. Experimental results demonstrate that, by changing the
      Riemannian metric, the registrations are always diffeomorphic, with higher
      qualities in terms of landmark alignment, curvature matching, area distortion and
      overlapping of region of interests.

PMID- 24683967
TI  - Geometric tree kernels: classification of COPD from airway tree geometry.
AB  - Methodological contributions: This paper introduces a family of kernels for
      analyzing (anatomical) trees endowed with vector valued measurements made along
      the tree. While state-of-the-art graph and tree kernels use combinatorial
      tree/graph structure with discrete node and edge labels, the kernels presented in
      this paper can include geometric information such as branch shape, branch radius
      or other vector valued properties. In addition to being flexible in their ability
      to model different types of attributes, the presented kernels are computationally
      efficient and some of them can easily be computed for large datasets (N - 10.000)
      of trees with 30 - 600 branches. Combining the kernels with standard machine
      learning tools enables us to analyze the relation between disease and anatomical
      tree structure and geometry. Experimental results: The kernels are used to
      compare airway trees segmented from low-dose CT, endowed with branch shape
      descriptors and airway wall area percentage measurements made along the tree.
      Using kernelized hypothesis testing we show that the geometric airway trees are
      significantly differently distributed in patients with Chronic Obstructive
      Pulmonary Disease (COPD) than in healthy individuals. The geometric tree kernels
      also give a significant increase in the classification accuracy of COPD from
      geometric tree structure endowed with airway wall thickness measurements in
      comparison with state-of-the-art methods, giving further insight into the
      relationship between airway wall thickness and COPD. Software: Software for
      computing kernels and statistical tests is available at
      http://image.diku.dk/aasa/software.php.

PMID- 24683968
TI  - Segmenting the papillary muscles and the trabeculae from high resolution cardiac
      CT through restoration of topological handles.
AB  - We introduce a novel algorithm for segmenting the high resolution CT images of
      the left ventricle (LV), particularly the papillary muscles and the trabeculae.
      High quality segmentations of these structures are necessary in order to better
      understand the anatomical function and geometrical properties of LV. These fine
      structures, however, are extremely challenging to capture due to their delicate
      and complex nature in both geometry and topology. Our algorithm computes the
      potential missing topological structures of a given initial segmentation. Using
      techniques from computational topology, e.g. persistent homology, our algorithm
      find topological handles which are likely to be the true signal. To further
      increase accuracy, these proposals are measured by the saliency and confidence
      from a trained classifier. Handles with high scores are restored in the final
      segmentation, leading to high quality segmentation results of the complex
      structures.

PMID- 24683969
TI  - Data-driven interactive 3D medical image segmentation based on structured patch
      model.
AB  - In this paper, we present a novel three dimensional interactive medical image
      segmentation method based on high level knowledge of training set. Since the
      interactive system should provide intermediate results to an user quickly,
      insufficient low level models are used for most of previous methods. To exploit
      the high level knowledge within a short time, we construct a structured patch
      model that consists of multiple corresponding patch sets. The structured patch
      model includes the spatial relationships between neighboring patch sets and the
      prior knowledge of the corresponding patch set on each local region. The spatial
      relationships accelerate the search of corresponding patch in test time, while
      the prior knowledge improves the segmentation accuracy. The proposed framework
      provides not only fast editing tool, but the incremental learning system through
      adding the segmentation result to the training set. Experiments demonstrate that
      the proposed method is useful for fast and accurate segmentation of target
      objects from the multiple medical images.

PMID- 24683970
TI  - Sparse deformable models with application to cardiac motion analysis.
AB  - Deformable models have been widely used with success in medical image analysis.
      They combine bottom-up information derived from image appearance cues, with top
      down shape-based constraints within a physics-based formulation. However, in many
      real world problems the observations extracted from the image data often contain
      gross errors, which adversely affect the deformation accuracy. To alleviate this
      issue, we introduce a new family of deformable models that are inspired from
      compressed sensing, a technique for efficiently reconstructing a signal based on
      its sparseness in some domain. In this problem, we employ sparsity to represent
      the outliers or gross errors, and combine it seamlessly with deformable models.
      The proposed new formulation is applied to the analysis of cardiac motion, using
      tagged magnetic resonance imaging (tMRI), where the automated tagging line
      tracking results are very noisy due to the poor image quality. Our new deformable
      models track the heart motion robustly, and the resulting strains are consistent
      with those calculated from manual labels.

PMID- 24683971
TI  - A longitudinal functional analysis framework for analysis of white matter tract
      statistics.
AB  - Many longitudinal imaging studies have been/are being widely conducted to use
      diffusion tensor imaging (DTI) to better understand white matter maturation in
      normal controls and diseased subjects. There is an urgent demand for the
      development of statistical methods for analyzing diffusion properties along major
      fiber tracts obtained from longitudinal DTI studies. Jointly analyzing fiber
      tract diffusion properties and covariates from longitudinal studies raises
      several major challenges including (i) infinite-dimensional functional response
      data, (ii) complex spatial-temporal correlation structure, and (iii) complex
      spatial smoothness. To address these challenges, this article is to develop a
      longitudinal functional analysis framework (LFAF) to delineate the dynamic
      changes of diffusion properties along major fiber tracts and their association
      with a set of covariates of interest (e.g., age and group status) and the
      structure of the variability of these white matter tract properties in various
      longitudinal studies. Our LFAF consists of a functional mixed effects model for
      addressing all three challenges, an efficient method for spatially smoothing
      varying coefficient functions, an estimation method for estimating the spatial
      temporal correlation structure, a test procedure with a global test statistic for
      testing hypotheses of interest associated with functional response, and a
      simultaneous confidence band for quantifying the uncertainty in the estimated
      coefficient functions. Simulated data are used to evaluate the finite sample
      performance of LFAF and to demonstrate that LFAF significantly outperforms a
      voxel-wise mixed model method. We apply LFAF to study the spatial-temporal
      dynamics of white-matter fiber tracts in a clinical study of neurodevelopment.

PMID- 24683972
TI  - Groupwise simultaneous manifold alignment for high-resolution dynamic MR imaging
      of respiratory motion.
AB  - Respiratory motion is a complicating factor for many applications in medical
      imaging and there is significant interest in dynamic imaging that can be used to
      estimate such motion. Magnetic resonance imaging (MRI) is an attractive modality
      for motion estimation but current techniques cannot achieve good image contrast
      inside the lungs. Manifold learning is a powerful tool to discover the underlying
      structure of high-dimensional data. Aligning the manifolds of multiple datasets
      can be useful to establish relationships between different types of data.
      However, the current state-of-the-art in manifold alignment is not robust to the
      wide variations in manifold structure that may occur in clinical datasets. In
      this work we propose a novel, fully automatic technique for the simultaneous
      alignment of large numbers of manifolds with varying manifold structure. We apply
      the technique to reconstruct high-resolution and high-contrast dynamic 3D MRI
      images from multiple 2D datasets for the purpose of respiratory motion
      estimation. The proposed method is validated on synthetic data with known ground
      truth and real data. We demonstrate that our approach can be applied to
      reconstruct significantly more accurate and consistent dynamic images of the
      lungs compared to the current state-of-the-art in manifold alignment.

PMID- 24683973
TI  - Conformal mapping via metric optimization with application for cortical label
      fusion.
AB  - In this paper we develop a novel approach for computing conformal maps between
      anatomical surfaces with the ability of aligning anatomical features and
      achieving greatly reduced metric distortion. In contrast to conventional
      approaches that focused on conformal maps to the sphere or plane, our method
      computes the conformal map between surfaces in the embedding space formed the
      intrinsically defined Laplace-Beltrami (LB) eigenfunctions. Utilizing the power
      of LB eigenfunctions as informative descriptors of global geometry, the conformal
      maps computed by our method can effectively align anatomical features on cortical
      surfaces. By computing such feature-aware conformal maps to a group-wisely
      optimal atlas surface, which is also computed with metric optimization in the LB
      embedding space, we develop a fully automated system for cortical labeling with
      the fusion of labels on a large number of atlas surfaces. In our experiments, we
      build our system with 40 labeled surfaces and demonstrate its excellent
      performance with leave-one-out cross validation. We also applied the automated
      labeling system to cortical surfaces reconstructed from MR scans of 50 patients
      with Alzheimer's disease (AD) and 50 normal controls (NC) to illustrate its
      robustness and effectiveness in clinical data analysis.

PMID- 24683974
TI  - A novel sparse group Gaussian graphical model for functional connectivity
      estimation.
AB  - The estimation of intra-subject functional connectivity is greatly complicated by
      the small sample size and complex noise structure in functional magnetic
      resonance imaging (fMRI) data. Pooling samples across subjects improves the
      conditioning of the estimation, but loses subject-specific connectivity
      information. In this paper, we propose a new sparse group Gaussian graphical
      model (SGGGM) that facilitates joint estimation of intra-subject and group-level
      connectivity. This is achieved by casting functional connectivity estimation as a
      regularized consensus optimization problem, in which information across subjects
      is aggregated in learning group-level connectivity and group information is
      propagated back in estimating intra-subject connectivity. On synthetic data, we
      show that incorporating group information using SGGGM significantly enhances
      intra-subject connectivity estimation over existing techniques. More accurate
      group-level connectivity is also obtained. On real data from a cohort of 60
      subjects, we show that integrating intra-subject connectivity estimated with
      SGGGM significantly improves brain activation detection over connectivity priors
      derived from other graphical modeling approaches.

PMID- 24683975
TI  - Joint co-segmentation and registration of 3D ultrasound images.
AB  - Contrast-enhanced ultrasound (CEUS) allows a visualization of the vascularization
      and complements the anatomical information provided by conventional ultrasound
      (US). However, these images are inherently subject to noise and shadows, which
      hinders standard segmentation algorithms. In this paper, we propose to use
      simultaneously the different information coming from 3D US and CEUS images to
      address the problem of kidney segmentation. To that end, we introduce a generic
      framework for joint co-segmentation and registration that seeks objects having
      the same shape in several images. From this framework, we derive both an
      ellipsoid co-detection and a model-based co-segmentation algorithm. These methods
      rely on voxel-classification maps that we estimate using random forests in a
      structured way. This yields a fast and fully automated pipeline, in which an
      ellipsoid is first estimated to locate the kidney in both US and CEUS volumes and
      then deformed to segment it accurately. The proposed method outperforms state-of
      the-art results (by dividing the kidney volume error by two) on a clinically
      representative database of 64 images.

PMID- 24683976
TI  - Deformable modeling using a 3D boundary representation with quadratic constraints
      on the branching structure of the Blum skeleton.
AB  - We propose a new approach for statistical shape analysis of 3D anatomical objects
      based on features extracted from skeletons. Like prior work on medial
      representations, the approach involves deforming a template to target shapes in a
      way that preserves the branching structure of the skeleton and provides
      intersubject correspondence. However, unlike medial representations, which
      parameterize the skeleton surfaces explicitly, our representation is boundary
      centric, and the skeleton is implicit. Similar to prior constrained modeling
      methods developed 2D objects or tube-like 3D objects, we impose symmetry
      constraints on tuples of boundary points in a way that guarantees the
      preservation of the skeleton's topology under deformation. Once discretized, the
      problem of deforming a template to a target shape is formulated as a
      quadratically constrained quadratic programming problem. The new technique is
      evaluated in terms of its ability to capture the shape of the corpus callosum
      tract extracted from diffusion-weighted MRI.

PMID- 24683977
TI  - Sparse projections of medical images onto manifolds.
AB  - Manifold learning has been successfully applied to a variety of medical imaging
      problems. Its use in real-time applications requires fast projection onto the low
      dimensional space. To this end, out-of-sample extensions are applied by
      constructing an interpolation function that maps from the input space to the low
      dimensional manifold. Commonly used approaches such as the Nystrom extension and
      kernel ridge regression require using all training points. We propose an
      interpolation function that only depends on a small subset of the input training
      data. Consequently, in the testing phase each new point only needs to be compared
      against a small number of input training data in order to project the point onto
      the low-dimensional space. We interpret our method as an out-of-sample extension
      that approximates kernel ridge regression. Our method involves solving a simple
      convex optimization problem and has the attractive property of guaranteeing an
      upper bound on the approximation error, which is crucial for medical
      applications. Tuning this error bound controls the sparsity of the resulting
      interpolation function. We illustrate our method in two clinical applications
      that require fast mapping of input images onto a low-dimensional space.

PMID- 24683978
TI  - Efficient 3D multi-region prostate MRI segmentation using dual optimization.
AB  - Efficient and accurate extraction of the prostate, in particular its clinically
      meaningful sub-regions from 3D MR images, is of great interest in image-guided
      prostate interventions and diagnosis of prostate cancer. In this work, we propose
      a novel multi-region segmentation approach to simultaneously locating the
      boundaries of the prostate and its two major sub-regions: the central gland and
      the peripheral zone. The proposed method utilizes the prior knowledge of the
      spatial region consistency and employs a customized prostate appearance model to
      simultaneously segment multiple clinically meaningful regions. We solve the
      resulted challenging combinatorial optimization problem by means of convex
      relaxation, for which we introduce a novel spatially continuous flow-maximization
      model and demonstrate its duality to the investigated convex relaxed optimization
      problem with the region consistency constraint. Moreover, the proposed continuous
      max-flow model naturally leads to a new and efficient continuous max-flow based
      algorithm, which enjoys great advantages in numerics and can be readily
      implemented on GPUs. Experiments using 15 T2-weighted 3D prostate MR images, by
      inter- and intra-operator variability, demonstrate the promising performance of
      the proposed approach.

PMID- 24683979
TI  - Locality preserving non-negative basis learning with graph embedding.
AB  - The high dimensionality of connectivity networks necessitates the development of
      methods identifying the connectivity building blocks that not only characterize
      the patterns of brain pathology but also reveal representative population
      patterns. In this paper, we present a non-negative component analysis framework
      for learning localized and sparse sub-network patterns of connectivity matrices
      by decomposing them into two sets of discriminative and reconstructive bases. In
      order to obtain components that are designed towards extracting population
      differences, we exploit the geometry of the population by using a
      graphtheoretical scheme that imposes locality-preserving properties as well as
      maintaining the underlying distance between distant nodes in the original and the
      projected space. The effectiveness of the proposed framework is demonstrated by
      applying it to two clinical studies using connectivity matrices derived from DTI
      to study a population of subjects with ASD, as well as a developmental study of
      structural brain connectivity that extracts gender differences.

PMID- 24683980
TI  - Hierarchical discriminative framework for detecting tubular structures in 3D
      images.
AB  - Detecting tubular structures such as airways or vessels in medical images is
      important for diagnosis and surgical planning. Many state-of-the-art approaches
      address this problem by starting from the root and progressing towards thinnest
      tubular structures usually guided by image filtering techniques. These approaches
      need to be tailored for each application and can fail in noisy or low-contrast
      regions. In this work, we address these challenges by a two-layer model which
      consists of a low-level likelihood measure and a high-level measure verifying
      tubular branches. The algorithm starts by computing a robust measure of tubular
      presence using a discriminative classifier at multiple image scales. The measure
      is then used in an efficient multi-scale shortest path algorithm to generate
      candidate centerline branches and corresponding radii measurements. Finally, the
      branches are verified by a learning-based indicator function that discards false
      candidate branches. The experiments on detecting airways in rotational X-ray
      volumes show that the technique is robust to noise and correctly finds airways
      even in the presence of imaging artifacts.

PMID- 24683981
TI  - Joint fractional segmentation and multi-tensor estimation in diffusion MRI.
AB  - In this paper we present a novel Bayesian approach for fractional segmentation of
      white matter tracts and simultaneous estimation of a multi-tensor diffusion
      model. Our model consists of several white matter tracts, each with a
      corresponding weight and tensor compartment in each voxel. By incorporating a
      prior that assumes the tensor fields inside each tract are spatially correlated,
      we are able to reliably estimate multiple tensor compartments in fiber crossing
      regions, even with low angular diffusion-weighted imaging (DWI). Our model
      distinguishes the diffusion compartment associated with each tract, which reduces
      the effects of partial voluming and achieves more reliable statistics of
      diffusion measurements. We test our method on synthetic data with known ground
      truth and show that we can recover the correct volume fractions and tensor
      compartments. We also demonstrate that the proposed method results in improved
      segmentation and diffusion measurement statistics on real data in the presence of
      crossing tracts and partial voluming.

PMID- 24683982
TI  - Retrospective estimation of the susceptibility driven field map for distortion
      correction in echo planar imaging.
AB  - Echo planar imaging (EPI) sequence used for acquiring functional MRI (fMRI) time
      series data provides the advantage of high temporal resolution, but also is
      highly sensitive to the magnetic field inhomogeneity resulting in geometric
      distortions. A static field-inhomogeneity map measured before or after the fMRI
      scan to correct for such distortions does not account for magnetic field changes
      due to the head motion during the time series acquisition. In practice, the field
      map dynamically changes with head motion during the scan and leads to variations
      in the geometric distortion. We model in this work the field inhomogeneity with
      the object and the scanner dependent terms. The object-specific term varies with
      the object's magnetic susceptibility and orientation, i.e., head position with
      respect to B0. Thus, the simple transformation of the acquired field may not
      yield an accurate field map. We assume that the scanner-specific field remains
      unchanged and independent of the head motion. Our approach in this study is to
      retrospectively estimate the object's magnetic susceptibility (chi) map from an
      observed high-resolution static field map using an estimator derived from a
      probability density function of non-uniform noise. This approach is capable of
      finding the susceptibility map regardless of the wrapping effect. A dynamic field
      map at each head position can be estimated by applying a rigid body
      transformation to the estimated chi-map and the 3-D susceptibility voxel
      convolution (SVC) which is a physics-based discrete convolution model for
      computing chi-induced field inhomogeneity.

PMID- 24683983
TI  - Group-wise cortical correspondence via sulcal curve-constrained entropy
      minimization.
AB  - We present a novel cortical correspondence method employing group-wise
      registration in a spherical parametrization space for the use in local cortical
      thickness analysis in human and non-human primate neuroimaging studies. The
      proposed method is unbiased registration that estimates a continuous smooth
      deformation field into an unbiased average space via sulcal curve-constrained
      entropy minimization using spherical harmonic decomposition of the spherical
      deformation field. We initialize a correspondence by our pair-wise method that
      establishes a surface correspondence with a prior template. Since this pair-wise
      correspondence is biased to the choice of a template, we further improve the
      correspondence by employing unbiased ensemble entropy minimization across all
      surfaces, which yields a deformation field onto the iteratively updated unbiased
      average. The specific entropy metric incorporates two terms: the first focused on
      optimizing the correspondence of automatically extracted sulcal landmarks and the
      second on that of sulcal depth maps. We also propose an encoding scheme for
      spherical deformation via spherical harmonics as well as a novel method to choose
      an optimal spherical polar coordinate system for the most efficient deformation
      field estimation. The experimental results show evidence that the proposed method
      improves the correspondence quality in non-human primate and human subjects as
      compared to the pair-wise method.

PMID- 24683984
TI  - Diffeomorphic spectral matching of cortical surfaces.
AB  - Accurate matching of cortical surfaces is necessary in many neuroscience
      applications. In this context diffeomorphisms are often sought, because they
      facilitate further statistical analysis and atlas building. Present methods for
      computing diffeomorphisms are based on optimizing flows or on inflating surfaces
      to a common template, but they are often computationally expensive. It typically
      takes several hours on a conventional desktop computer to match a single pair of
      cortical surfaces having a few hundred thousand vertices. We propose a very fast
      alternative based on an application of spectral graph theory on a novel
      association graph. Our symmetric approach can generate a diffeomorphic
      correspondence map within a few minutes on high-resolution meshes while avoiding
      the sign and multiplicity ambiguities of conventional spectral matching methods.
      The eigenfunctions are shared between surfaces and provide a smooth
      parameterization of surfaces. These properties are exploited to compute
      differentials on highly folded cortical surfaces. Diffeomorphisms can thus be
      verified and invalid surface folding detected. Our method is demonstrated to
      attain a vertex accuracy that is at least as good as that of FreeSurfer and
      Spherical Demons but in only a fraction of their processing time. As a practical
      experiment, we construct an unbiased atlas of cortical surfaces with a speed
      several orders of magnitude faster than current methods.

PMID- 24683985
TI  - The non-local bootstrap--estimation of uncertainty in diffusion MRI.
AB  - Diffusion MRI is a noninvasive imaging modality that allows for the estimation
      and visualization of white matter connectivity patterns in the human brain.
      However, due to the low signal-to-noise ratio (SNR) nature of diffusion data,
      deriving useful statistics from the data is adversely affected by different
      sources of measurement noise. This is aggravated by the fact that the sampling
      distribution of the statistic of interest is often complex and unknown. In
      situations as such, the bootstrap, due to its distribution-independent nature, is
      an appealing tool for the estimation of the variability of almost any statistic,
      without relying on complicated theoretical calculations, but purely on computer
      simulation. In this work, we present new bootstrap strategies for variability
      estimation of diffusion statistics in association with noise. In contrast to the
      residual bootstrap, which relies on a predetermined data model, or the repetition
      bootstrap, which requires repeated signal measurements, our approach, called the
      non-local bootstrap (NLB), is non-parametric and obviates the need for time
      consuming multiple acquisitions. The key assumption of NLB is that local image
      structures recur in the image. We exploit this self-similarity via a multivariate
      non-parametric kernel regression framework for bootstrap estimation of
      uncertainty. Evaluation of NLB using a set of high-resolution diffusion-weighted
      images, with lower than usual SNR due to the small voxel size, indicates that NLB
      is markedly more robust to noise and results in more accurate inferences.

PMID- 24683986
TI  - Beyond crossing fibers: tractography exploiting sub-voxel fibre dispersion and
      neighbourhood structure.
AB  - In this paper we propose a novel algorithm which leverages models of white matter
      fibre dispersion to improve tractography. Tractography methods exploit
      directional information from diffusion weighted magnetic resonance (DW-MR)
      imaging to infer connectivity between different brain regions. Most tractography
      methods use a single direction (e.g. the principal eigenvector of the diffusion
      tensor) or a small set of discrete directions (e.g. from the peaks of an
      orientation distribution function) to guide streamline propagation. This strategy
      ignores the effects of within-bundle orientation dispersion, which arises from
      fanning or bending at the sub-voxel scale, and can lead to missing connections.
      Various recent DW-MR imaging techniques estimate the fibre dispersion in each
      bundle directly and model it as a continuous distribution. Here we introduce an
      algorithm to exploit this information to improve tractography. The algorithm
      further uses a particle filter to probe local neighbourhood structure during
      streamline propagation. Using information gathered from neighbourhood structure
      enables the algorithm to resolve ambiguities between converging and diverging
      fanning structures, which cannot be distinguished from isolated orientation
      distribution functions. We demonstrate the advantages of the new approach in
      synthetic experiments and in vivo data. Synthetic experiments demonstrate the
      effectiveness of the particle filter in gathering and exploiting neighbourhood
      information in recovering various canonical fibre configurations and experiments
      with in vivo brain data demonstrate the advantages of utilising dispersion in
      tractography, providing benefits in practical situations.

PMID- 24683987
TI  - Learning from M/EEG data with variable brain activation delays.
AB  - Magneto- and electroencephalography (M/EEG) measure the electromagnetic signals
      produced by brain activity. In order to address the issue of limited signal-to
      noise ratio (SNR) with raw data, acquisitions consist of multiple repetitions of
      the same experiment. An important challenge arising from such data is the
      variability of brain activations over the repetitions. It hinders statistical
      analysis such as prediction performance in a supervised learning setup. One such
      confounding variability is the time offset of the peak of the activation, which
      varies across repetitions. We propose to address this misalignment issue by
      explicitly modeling time shifts of different brain responses in a classification
      setup. To this end, we use the latent support vector machine (LSVM) formulation,
      where the latent shifts are inferred while learning the classifier parameters.
      The inferred shifts are further used to improve the SNR of the M/EEG data, and to
      infer the chronometry and the sequence of activations across the brain regions
      that are involved in the experimental task. Results are validated on a long-term
      memory retrieval task, showing significant improvement using the proposed latent
      discriminative method.

PMID- 24683988
TI  - Unsupervised learning of functional network dynamics in resting state fMRI.
AB  - Research in recent years has provided some evidence of temporal non-stationarity
      of functional connectivity in resting state fMRI. In this paper, we present a
      novel methodology that can decode connectivity dynamics into a temporal sequence
      of hidden network "states" for each subject, using a Hidden Markov Modeling (HMM)
      framework. Each state is characterized by a unique covariance matrix or whole
      brain network. Our model generates these covariance matrices from a common but
      unknown set of sparse basis networks, which capture the range of functional
      activity co-variations of regions of interest (ROIs). Distinct hidden states
      arise due to a variation in the strengths of these basis networks. Thus, our
      generative model combines a HMM framework with sparse basis learning of positive
      definite matrices. Results on simulated fMRI data show that our method can
      effectively recover underlying basis networks as well as hidden states. We apply
      this method on a normative dataset of resting state fMRI scans. Results indicate
      that the functional activity of a subject at any point during the scan is
      composed of combinations of overlapping task-positive/negative pairs of networks
      as revealed by our basis. Distinct hidden temporal states are produced due to a
      different set of basis networks dominating the covariance pattern in each state.

PMID- 24683989
TI  - Cohort-level brain mapping: learning cognitive atoms to single out specialized
      regions.
AB  - Functional Magnetic Resonance Imaging (fMRI) studies map the human brain by
      testing the response of groups of individuals to carefully-crafted and contrasted
      tasks in order to delineate specialized brain regions and networks. The number of
      functional networks extracted is limited by the number of subject-level contrasts
      and does not grow with the cohort. Here, we introduce a new group-level brain
      mapping strategy to differentiate many regions reflecting the variety of brain
      network configurations observed in the population. Based on the principle of
      functional segregation, our approach singles out functionally-specialized brain
      regions by learning group-level functional profiles on which the response of
      brain regions can be represented sparsely. We use a dictionary-learning
      formulation that can be solved efficiently with on-line algorithms, scaling to
      arbitrary large datasets. Importantly, we model inter-subject correspondence as
      structure imposed in the estimated functional profiles, integrating a structure
      inducing regularization with no additional computational cost. On a large multi
      subject study, our approach extracts a large number of brain networks with
      meaningful functional profiles.

PMID- 24683990
TI  - Rapid multi-organ segmentation using context integration and discriminative
      models.
AB  - We propose a novel framework for rapid and accurate segmentation of a cohort of
      organs. First, it integrates local and global image context through a product
      rule to simultaneously detect multiple landmarks on the target organs. The global
      posterior integrates evidence over all volume patches, while the local image
      context is modeled with a local discriminative classifier. Through non-parametric
      modeling of the global posterior, it exploits sparsity in the global context for
      efficient detection. The complete surface of the target organs is then inferred
      by robust alignment of a shape model to the resulting landmarks and finally
      deformed using discriminative boundary detectors. Using our approach, we
      demonstrate efficient detection and accurate segmentation of liver, kidneys,
      heart, and lungs in challenging low-resolution MR data in less than one second,
      and of prostate, bladder, rectum, and femoral heads in CT scans, in roughly one
      to three seconds and in both cases with accuracy fairly close to inter-user
      variability.

PMID- 24683991
TI  - Edge- and detail-preserving sparse image representations for deformable
      registration of chest MRI and CT volumes.
AB  - Deformable medical image registration requires the optimisation of a function
      with a large number of degrees of freedom. Commonly-used approaches to reduce the
      computational complexity, such as uniform B-splines and Gaussian image pyramids,
      introduce translation-invariant homogeneous smoothing, and may lead to less
      accurate registration in particular for motion fields with discontinuities. This
      paper introduces the concept of sparse image representation based on supervoxels,
      which are edge-preserving and therefore enable accurate modelling of sliding
      organ motions frequently seen in respiratory and cardiac scans. Previous
      shortcomings of using supervoxels in motion estimation, in particular
      inconsistent clustering in ambiguous regions, are overcome by employing multiple
      layers of supervoxels. Furthermore, we propose a new similarity criterion based
      on a binary shape representation of supervoxels, which improves the accuracy of
      single-modal registration and enables multimodal registration. We validate our
      findings based on the registration of two challenging clinical applications of
      volumetric deformable registration: motion estimation between inhale and exhale
      phase of CT scans for radiotherapy planning, and deformable multi-modal
      registration of diagnostic MRI and CT chest scans. The experiments demonstrate
      state-of-the-art registration accuracy, and require no additional anatomical
      knowledge with greatly reduced computational complexity.

PMID- 24683992
TI  - Multimodal surface matching: fast and generalisable cortical registration using
      discrete optimisation.
AB  - Group neuroimaging studies of the cerebral cortex benefit from accurate, surface
      based, cross-subject alignment for investigating brain architecture, function and
      connectivity. There is an increasing amount of high quality data available.
      However, establishing how different modalities correlate across groups remains an
      open research question. One reason for this is that the current methods for
      registration, based on cortical folding, provide sub-optimal alignment of some
      functional subregions of the brain. A more flexible framework is needed that will
      allow robust alignment of multiple modalities. We adapt the Fast Primal-Dual
      (Fast-PD) approach for discrete Markov Random Field (MRF) optimisation to
      spherical registration by reframing the deformation labels as a discrete set of
      rotations and propose a novel regularisation term, derived from the geodesic
      distance between rotation matrices. This formulation allows significant
      flexibility in the choice of similarity metric. To this end we propose a new
      multivariate cost function based on the discretisation of a graph-based mutual
      information measure. Results are presented for alignment driven by scalar metrics
      of curvature and myelination, and multivariate features derived from functional
      task performance. These experiments demonstrate the potential of this approach
      for improving the integration of complementary brain data sets in the future.

PMID- 24683993
TI  - Globally optimal cortical surface matching with exact landmark correspondence.
AB  - We present a method for establishing correspondences between human cortical
      surfaces that exactly matches the positions of given point landmarks, while
      attaining the global minimum of an objective function that quantifies how far the
      mapping deviates from conformality. On each surface, a conformal transformation
      is applied to the Euclidean distance metric, resulting in a hyperbolic metric
      with isolated cone point singularities at the landmarks. Equivalently, each
      surface is mapped to a hyperbolic orbifold: a pillow-like surface with each point
      landmark corresponding to a pillow corner. An initial surface-to-surface mapping
      exactly aligns the landmarks, and gradient descent is used to find the single,
      global minimum of the Dirichlet energy of the remainder of the mapping. Using a
      population of real MRI-based cortical surfaces with manually labeled sulcus
      endpoints as landmarks, we evaluate the approach by how much it distorts surfaces
      and by its biological plausibility: how well it aligns previously-unseen
      anatomical landmarks and by how well it promotes expected associations between
      cortical thickness and age. We show that, compared to a painstakingly-tuned
      approach that balances a tradeoff between minimizing landmark mismatch and
      Dirichlet energy, our method has similar biological plausibility, superior
      surface distortion, a better theoretical foundation, and fewer arbitrary
      parameters to tune. We also compare to conformal mapper in the spherical domain
      to show that sacrificing exact conformality of the mapping does not cause
      noticeable reductions in biological plausibility.

PMID- 24683994
TI  - Joint learning of appearance and transformation for predicting brain MR image
      registration.
AB  - We propose a new approach to register the subject image with the template by
      leveraging a set of training images that are pre-aligned to the template. We
      argue that, if voxels in the subject and the training images share similar local
      appearances and transformations, they may have common correspondence in the
      template. In this way, we learn the sparse representation of certain subject
      voxel to reveal several similar candidate voxels in the training images. Each
      selected training candidate can bridge the correspondence from the subject voxel
      to the template space, thus predicting the transformation associated with the
      subject voxel at the confidence level that relates to the learned sparse
      coefficient. Following this strategy, we first predict transformations at
      selected key points, and retain multiple predictions on each key point (instead
      of allowing a single correspondence only). Then, by utilizing all key points and
      their predictions with varying confidences, we adaptively reconstruct the dense
      transformation field that warps the subject to the template. For robustness and
      computation speed, we embed the prediction-reconstruction protocol above into a
      multi-resolution hierarchy. In the final, we efficiently refine our estimated
      transformation field via existing registration method. We apply our method to
      registering brain MR images, and conclude that the proposed method is competent
      to improve registration performances in terms of time cost as well as accuracy.

PMID- 24683995
TI  - Automatic prostate MR image segmentation with sparse label propagation and domain
      specific manifold regularization.
AB  - Automatic prostate segmentation in MR images plays an important role in prostate
      cancer diagnosis. However, there are two main challenges: (1) Large inter-subject
      prostate shape variations; (2) Inhomogeneous prostate appearance. To address
      these challenges, we propose a new hierarchical prostate MR segmentation method,
      with the main contributions lying in the following aspects: First, the most
      salient features are learnt from atlases based on a subclass discriminant
      analysis (SDA) method, which aims to find a discriminant feature subspace by
      simultaneously maximizing the inter-class distance and minimizing the intra-class
      variations. The projected features, instead of only voxel-wise intensity, will be
      served as anatomical signature of each voxel. Second, based on the projected
      features, a new multi-atlases sparse label fusion framework is proposed to
      estimate the prostate likelihood of each voxel in the target image from the
      coarse level. Third, a domain-specific semi-supervised manifold regularization
      method is proposed to incorporate the most reliable patient-specific information
      identified by the prostate likelihood map to refine the segmentation result from
      the fine level. Our method is evaluated on a T2 weighted prostate MR image
      dataset consisting of 66 patients and compared with two state-of-the-art
      segmentation methods. Experimental results show that our method consistently
      achieves the highest segmentation accuracies than other methods under comparison.

PMID- 24683996
TI  - Moving frames for heart fiber geometry.
AB  - Elongated cardiac muscle cells named cardiomyocytes are densely packed in an
      intercellular collagen matrix and are aligned to helical segments in a manner
      which facilitates pumping via alternate contraction and relaxation.
      Characterizing the geometrical variation of their groupings as cardiac fibers is
      central to our understanding of normal heart function. Motivated by a recent
      abstraction by Savadjiev et al. of heart wall fibers into generalized helicoid
      minimal surfaces, this paper develops an extension based on differential forms.
      The key idea is to use Maurer-Cartan's method of moving frames to study the
      rotations of a frame field attached to the local fiber direction. This approach
      provides a new set of parameters that are complimentary to those of Savadjiev et
      al. and offers a framework for developing new models of the cardiac fiber
      architecture. This framework is used to compute the generalized helicoid
      parameters directly, without the need to formulate an optimization problem. The
      framework admits a straightforward numerical implementation that provides
      statistical measurements consistent with those previously reported. Using
      Diffusion MRI we demonstrate that one such specialization, the homeoid,
      constrains fibers to lie locally within ellipsoidal shells and yields improved
      fits in the rat, the dog and the human to those obtained using generalized
      helicoids.

PMID- 24683997
TI  - Structural brain network constrained neuroimaging marker identification for
      predicting cognitive functions.
AB  - Neuroimaging markers have been widely used to predict the cognitive functions
      relevant to the progression of Alzheimer's disease (AD). Most previous studies
      identify the imaging markers without considering the brain structural
      correlations between neuroimaging measures. However, many neuroimaging markers
      interrelate and work together to reveal the cognitive functions, such that these
      relevant markers should be selected together as the phenotypic markers. To solve
      this problem, in this paper, we propose a novel network constrained feature
      selection (NCFS) model to identify the neuroimaging markers guided by the
      structural brain network, which is constructed by the sparse representation
      method such that the interrelations between neuroimaging features are encoded
      into probabilities. Our new methods are evaluated by the MRI and AV45-PET data
      from ADNI-GO and ADNI-2 (Alzheimer's Disease Neuroimaging Initiative). In all
      cognitive function prediction tasks, our new NCFS method outperforms other state
      of-the-art regression approaches. Meanwhile, we show that the new method can
      select the correlated imaging markers, which are ignored by the competing
      approaches.

PMID- 24683998
TI  - Multi-atlas segmentation with robust label transfer and label fusion.
AB  - Multi-atlas segmentation has been widely applied in medical image analysis. This
      technique relies on image registration to transfer segmentation labels from pre
      labeled atlases to a novel target image and applies label fusion to reduce errors
      produced by registration-based label transfer. To improve the performance of
      registration-based label transfer against registration errors, our first
      contribution is to propose a label transfer scheme that generates multiple warped
      versions of each atlas to one target image through registration paths obtained by
      composing inter-atlas registrations and atlas-target registrations. The problem
      of decreasing quality of warped atlases caused by accumulative errors in
      composing multiple registrations is properly addressed by an atlas selection
      method that is guided by atlas segmentations. To improve the performance of label
      fusion against registration errors, our second contribution is to integrate the
      probabilistic correspondence model employed by the non-local mean approach with
      the joint label fusion technique, both of which have shown excellent performance
      for label fusion. Experiments on mitral-valve segmentation in 3D transesophageal
      echocardiography (TEE) show the effectiveness of the proposed techniques.

PMID- 24683999
TI  - A hierarchical geodesic model for diffeomorphic longitudinal shape analysis.
AB  - Hierarchical linear models (HLMs) are a standard approach for analyzing data
      where individuals are measured repeatedly over time. However, such models are
      only applicable to longitudinal studies of Euclidean data. In this paper, we
      propose a novel hierarchical geodesic model (HGM), which generalizes HLMs to the
      manifold setting. Our proposed model explains the longitudinal trends in shapes
      represented as elements of the group of diffeomorphisms. The individual level
      geodesics represent the trajectory of shape changes within individuals. The group
      level geodesic represents the average trajectory of shape changes for the
      population. We derive the solution of HGMs on diffeomorphisms to estimate
      individual level geodesics, the group geodesic, and the residual geodesics. We
      demonstrate the effectiveness of HGMs for longitudinal analysis of synthetically
      generated shapes and 3D MRI brain scans.

PMID- 24684000
TI  - Active testing search for point cloud matching.
AB  - We present a general approach for solving the point-cloud matching problem for
      the case of mildly nonlinear transformations. Our method quickly finds a coarse
      approximation of the solution by exploring a reduced set of partial matches using
      an approach to which we refer to as Active Testing Search (ATS). We apply the
      method to registration of graph structures by branching point matching. It is
      based solely on the geometric position of the points, no additional information
      is used nor the knowledge of an initial alignment. In the second stage, we use
      dynamic programming to refine the solution. We tested our algorithm on
      angiography, retinal fundus, and neuronal data gathered using electron and light
      microscopy. We show that our method solves cases not solved by most approaches,
      and is faster than the remaining ones.

PMID- 24684001
TI  - Relating Fisher information to detectability of changes in nodule characteristics
      with CT.
AB  - Fisher information provides a bound on the variance of any unbiased estimate for
      estimation tasks involving nonrandom parameters. In addition, a Fisher
      information approximation for ideal-observer detectability has been derived. We
      adopt and generalize such an approximation to establish a method to assess a
      system's ability to detect small changes in lesion characteristics. By
      representing the lesion by a size parameter, the ability to detect small changes
      can be approximated by a function involving the size difference and the Fisher
      information. A concept, termed the approximated least required difference (ALRD),
      is introduced and evaluated as an upper bound for assessing a system's power in
      size discrimination. We present a simulation study for lung nodules as an example
      to illustrate such a framework, where the image model incorporates a simulated CT
      imaging system, a thorax background and parameterized nodules. The noise is
      assumed to be multivariate Gaussian and the noise power spectrum (NPS) method is
      used to estimate the covariance matrix for the Fisher information calculation. In
      addition to bounding performance, our results also provide insights into factors,
      including nodule characteristics and acquisition parameters, that influence ALRD
      performance. This framework can be extended to connect other discrimination and
      estimation tasks, facilitating objective assessment and optimization of
      quantitative imaging systems.

PMID- 24684002
TI  - Adaptive multi-modal particle filtering for probabilistic white matter
      tractography.
AB  - Particle filtering has recently been introduced to perform probabilistic
      tractography in conjunction with DTI and Q-Ball models to estimate the diffusion
      information. Particle filters are particularly well adapted to the tractography
      problem as they offer a way to approximate a probability distribution over all
      paths originated from a specified voxel, given the diffusion information. In
      practice however, they often fail at consistently capturing the multi-modality of
      the target distribution. For brain white matter tractography, this means that
      multiple fiber pathways are unlikely to be tracked over extended volumes. We
      propose to remedy this issue by formulating the filtering distribution as an
      adaptive M-component non-parametric mixture model. Such a formulation preserves
      all the properties of a classical particle filter while improving multi-modality
      capture. We apply this multi-modal particle filter to both DTI and Q-Ball models
      and propose to estimate dynamically the number of modes of the filtering
      distribution. We show on synthetic and real data how this algorithm outperforms
      the previous versions proposed in the literature.

PMID- 24684003
TI  - Can T2-spectroscopy resolve submicrometer axon diameters?
AB  - The microscopic geometry of white matter carries rich information about brain
      function in health and disease. A key challenge for medical imaging is to
      estimate microstructural features noninvasively. One important parameter is the
      axon diameter, which correlates with the conduction time delay of action
      potentials and is affected by various neurological disorders. Diffusion magnetic
      resonance (MR) experiments are the method of choice today when we aim to recover
      the axon diameter distribution, although the technique requires very high
      gradient strengths in order to assess nerve fibers with one micrometer or less in
      diameter. In practice in-vivo brain imaging is only sensitive to the largest
      axons, not least due to limitations in the human physiology which tolerates only
      moderate gradient strengths. This work studies, from a theoretical perspective,
      the feasibility of T2-spectroscopy to resolve submicrometer tissue structures.
      Exploiting the surface relaxation effect, we formulate a plausible biophysical
      model relating the axon diameter distribution to the T2-weighted signal, which is
      based on a surface-to-volume ratio approximation of the Bloch-Torrey equation.
      Under a certain regime of bulk and surface relaxation coefficients, our
      simulation results suggest that it might be possible to reveal axons smaller than
      one micrometer in diameter.

PMID- 24684004
TI  - Dictionary learning on the manifold of square root densities and application to
      reconstruction of diffusion propagator fields.
AB  - In this paper, we present a novel dictionary learning framework for data lying on
      the manifold of square root densities and apply it to the reconstruction of
      diffusion propagator (DP) fields given a multi-shell diffusion MRI data set.
      Unlike most of the existing dictionary learning algorithms which rely on the
      assumption that the data points are vectors in some Euclidean space, our
      dictionary learning algorithm is designed to incorporate the intrinsic geometric
      structure of manifolds and performs better than traditional dictionary learning
      approaches when applied to data lying on the manifold of square root densities.
      Non-negativity as well as smoothness across the whole field of the reconstructed
      DPs is guaranteed in our approach. We demonstrate the advantage of our approach
      by comparing it with an existing dictionary based reconstruction method on
      synthetic and real multi-shell MRI data.

PMID- 24684005
TI  - Diseased region detection of longitudinal knee MRI data.
AB  - Statistical analysis of longitudinal cartilage changes in osteoarthritis (OA) is
      of great importance and still a challenge in knee MRI data analysis. A major
      challenge is to establish a reliable correspondence across subjects within the
      same latent subpopulations. We develop a novel Gaussian hidden Markov model
      (GHMM) to establish spatial correspondence of cartilage thinning across both time
      and subjects within the same latent subpopulations and make statistical inference
      on the detection of diseased regions in each OA patient. A hidden Markov random
      field (HMRF) is proposed to extract such latent subpopulation structure. The EM
      algorithm and pseudo-likelihood method are both considered in making statistical
      inference. The proposed model can effectively detect diseased regions and present
      a localized analysis of longitudinal cartilage thickness within each latent
      subpopulation. Simulation studies and diseased region detection on 2D thickness
      maps extracted from full 3D longitudinal knee MRI Data for Pfizer Longitudinal
      Dataset are performed, which show that our proposed model outperforms standard
      voxel-based analysis.

PMID- 24684006
TI  - Model selection and estimation of multi-compartment models in diffusion MRI with
      a Rician noise model.
AB  - Multi-compartment models in diffusion MRI (dMRI) are used to describe complex
      white matter fiber architecture of the brain. In this paper, we propose a novel
      multi-compartment estimation method based on the ball-and-stick model, which is
      composed of an isotropic diffusion compartment ("ball") as well as one or more
      perfectly linear diffusion compartments ("sticks"). To model the noise
      distribution intrinsic to dMRI measurements, we introduce a Rician likelihood
      term and estimate the model parameters by means of an Expectation Maximization
      (EM) algorithm. This paper also addresses the problem of selecting the number of
      fiber compartments that best fit the data, by introducing a sparsity prior on the
      volume mixing fractions. This term provides automatic model selection and enables
      us to discriminate different fiber populations. When applied to simulated data,
      our method provides accurate estimates of the fiber orientations, diffusivities,
      and number of compartments, even at low SNR, and outperforms similar methods that
      rely on a Gaussian noise distribution assumption. We also apply our method to in
      vivo brain data and show that it can successfully capture complex fiber
      structures that match the known anatomy.

PMID- 24684007
TI  - Bayesian segmentation of atrium wall using globally-optimal graph cuts on 3D
      meshes.
AB  - Efficient segmentation of the left atrium (LA) wall from delayed enhancement MRI
      is challenging due to inconsistent contrast, combined with noise, and high
      variation in atrial shape and size. We present a surface-detection method that is
      capable of extracting the atrial wall by computing an optimal a-posteriori
      estimate. This estimation is done on a set of nested meshes, constructed from an
      ensemble of segmented training images, and graph cuts on an associated multi
      column, proper-ordered graph. The graph/mesh is a part of a template/model that
      has an associated set of learned intensity features. When this mesh is overlaid
      onto a test image, it produces a set of costs which lead to an optimal
      segmentation. The 3D mesh has an associated weighted, directed multi-column graph
      with edges that encode smoothness and inter-surface penalties. Unlike previous
      graph-cut methods that impose hard constraints on the surface properties, the
      proposed method follows from a Bayesian formulation resulting in soft penalties
      on spatial variation of the cuts through the mesh. The novelty of this method
      also lies in the construction of proper-ordered graphs on complex shapes for
      choosing among distinct classes of base shapes for automatic LA segmentation. We
      evaluate the proposed segmentation framework on simulated and clinical cardiac
      MRI.

PMID- 24684008
TI  - Using region trajectories to construct an accurate and efficient polyaffine
      transform model.
AB  - In this paper we propose a novel way to construct a diffeomorphic polyaffine
      model. Each affine transform is defined on a local region and the resulting
      diffeomorphism encapsulates all the local transforms by a smooth and invertible
      displacement field. Compared with traditional weighting schemes used in combining
      local transforms, our new scheme guarantees that the resulting transform
      precisely preserves the value of each local affine transform. By introducing the
      trajectory of local regions instead of using regions themselves, the new approach
      encodes precisely each local affine transform using a diffeomorphism with one or
      more stationary velocity fields. Experiments show that our new polyaffine model
      is both accurate and efficient.

PMID- 24684009
TI  - Extracting evolving pathologies via spectral clustering.
AB  - A bottleneck in the analysis of longitudinal MR scans with white matter brain
      lesions is the temporally consistent segmentation of the pathology. We identify
      pathologies in 3D+t(ime) within a spectral graph clustering framework. Our
      clustering approach simultaneously segments and tracks the evolving lesions by
      identifying characteristic image patterns at each time-point and voxel
      correspondences across time-points. For each 3D image, our method constructs a
      graph where weights between nodes capture the likeliness of two voxels belonging
      to the same region. Based on these weights, we then establish rough
      correspondences between graph nodes at different time-points along estimated
      pathology evolution directions. We combine the graphs by aligning the weights to
      a reference time-point, thus integrating temporal information across the 3D
      images, and formulate the 3D+t segmentation problem as a binary partitioning of
      this graph. The resulting segmentation is very robust to local intensity
      fluctuations and yields better results than segmentations generated for each time
      point.

PMID- 24684010
TI  - Construction of multi-scale common brain networks based on DICCCOL.
AB  - Modeling the human brain as a network has been widely considered as a powerful
      approach to investigating the brain's structural and functional systems. However,
      many previous approaches focused on a single scale of brain network and the multi
      scale nature of brain networks has been rarely explored yet. This paper put
      forward a novel framework to construct multi-scale common networks of brains via
      multi-scale spectral clustering of fiber connections among DICCCOLs.
      Specifically, the recently developed and publicly released DICCCOLs provide the
      nodal structural and functional correspondence across individuals, and thus the
      employed multi-scale spectral clustering algorithm divided the DICCCOL landmarks
      and their connections into sub-networks with correspondences on multiple scales.
      Experimental results showed the promise of the constructed multi-scale networks
      in applications of structural and functional connectivity mapping. As an
      application example, these multi-scale networks are used to guide the
      identification of multi-scale common fiber bundles across individuals and to
      facilitate the bundle's functional role analysis, which could enable other tract
      based and network-based analyses in the future.

PMID- 24684011
TI  - Rotation invariant features for HARDI.
AB  - Reducing the amount of information stored in diffusion MRI (dMRI) data to a set
      of meaningful and representative scalar values is a goal of much interest in
      medical imaging. Such features can have far reaching applications in
      segmentation, registration, and statistical characterization of regions of
      interest in the brain, as in comparing features between control and diseased
      patients. Currently, however, the number of biologically relevant features in
      dMRI is very limited. Moreover, existing features discard much of the information
      inherent in dMRI and embody several theoretical shortcomings. This paper proposes
      a new family of rotation invariant scalar features for dMRI based on the
      spherical harmonic (SH) representation of high angular resolution diffusion
      images (HARDI). These features describe the shape of the orientation distribution
      function extracted from HARDI data and are applicable to any reconstruction
      method that represents HARDI signals in terms of an SH basis. We further
      illustrate their significance in white matter characterization of synthetic,
      phantom and real HARDI brain datasets.

PMID- 24684012
TI  - Geodesic shape regression in the framework of currents.
AB  - Shape regression is emerging as an important tool for the statistical analysis of
      time dependent shapes. In this paper, we develop a new generative model which
      describes shape change over time, by extending simple linear regression to the
      space of shapes represented as currents in the large deformation diffeomorphic
      metric mapping (LDDMM) framework. By analogy with linear regression, we estimate
      a baseline shape (intercept) and initial momenta (slope) which fully parameterize
      the geodesic shape evolution. This is in contrast to previous shape regression
      methods which assume the baseline shape is fixed. We further leverage a control
      point formulation, which provides a discrete and low dimensional parameterization
      of large diffeomorphic transformations. This flexible system decouples the
      parameterization of deformations from the specific shape representation, allowing
      the user to define the dimensionality of the deformation parameters. We present
      an optimization scheme that estimates the baseline shape, location of the control
      points, and initial momenta simultaneously via a single gradient descent
      algorithm. Finally, we demonstrate our proposed method on synthetic data as well
      as real anatomical shape complexes.

PMID- 24684013
TI  - Multinomial probabilistic fiber representation for connectivity driven
      clustering.
AB  - The clustering of fibers into bundles is an important task in studying the
      structure and function of white matter. Existing technology mostly relies on
      geometrical features, such as the shape of fibers, and thus only provides very
      limited information about the neuroanatomical function of the brain. We advance
      this issue by proposing a multinomial representation of fibers decoding their
      connectivity to gray matter regions. We then simplify the clustering task by
      first deriving a compact encoding of our representation via the logit
      transformation. Furthermore, we define a distance between fibers that is in
      theory invariant to parcellation biases and is equivalent to a family of
      Riemannian metrics on the simplex of multinomial probabilities. We apply our
      method to longitudinal scans of two healthy subjects showing high reproducibility
      of the resulting fiber bundles without needing to register the corresponding
      scans to a common coordinate system. We confirm these qualitative findings via a
      simple statistical analyse of the fiber bundles.

PMID- 24684014
TI  - Reliable selection of the number of fascicles in diffusion images by estimation
      of the generalization error.
AB  - A number of diffusion models have been proposed to overcome the limitations of
      diffusion tensor imaging (DTI) which cannot represent multiple fascicles with
      heterogeneous orientations at each voxel. Among them, generative models such as
      multi-tensor models, CHARMED or NODDI represent each fascicle with a parametric
      model and are of great interest to characterize and compare white matter
      properties. However, the identification of the appropriate model, and
      particularly the estimation of the number of fascicles, has proven challenging.
      In this context, different model selection approaches have been proposed to
      identify the number of fascicles at each voxel. Most approaches attempt to
      maximize the quality of fit while penalizing complex models to avoid overfitting.
      However, the choice of a penalization strategy and the trade-off between
      penalization and quality of fit are rather arbitrary and produce highly variable
      results. In this paper, we propose for the first time to determine the number of
      fascicles at each voxel by assessing the generalization error. This criterion
      naturally prevents overfitting by comparing how the models predict new data not
      included in the model estimation. Since the generalization error cannot be
      directly computed, we propose to estimate it by the 632 bootstrap technique which
      has low bias and low variance. Results on synthetic phantoms and in vivo data
      show that our approach performs better than existing techniques, and is robust to
      the choice of decision threshold. Together with generative models of the
      diffusion signal, this technique will enable accurate identification of the model
      complexity at each voxel and accurate assessment of the white matter
      characteristics.

PMID- 24684015
TI  - IDiff: irrotational diffeomorphisms for computational anatomy.
AB  - The study of diffeomorphism groups is fundamental to computational anatomy, and
      in particular to image registration. One of the most developed frameworks employs
      a Riemannian-geometric approach using right-invariant Sobolev metrics. To date,
      the computation of the Riemannian log and exponential maps on the diffeomorphism
      group have been defined implicitly via an infinite-dimensional optimization
      problem. In this paper we the employ Brenier's (1991) polar factorization to
      decompose a diffeomorphism h as h(chi) = S o psi(chi), where psi = deltarho is
      the gradient of a convex function p and S epsilon SDiff(R(d)) is a volume
      preserving diffeomorphism. We show that all such mappings psi form a submanifold,
      which we term IDiff(R(d)), generated by irrotational flows from the identity.
      Using the natural metric, the manifold IDiff(R(d)) is flat. This allows us to
      calculate the Riemannian log map on this submanifold of diffeomorphisms in closed
      form, and develop extremely efficient metric-based image registration algorithms.
      This result has far-reaching implications in terms of the statistical analysis of
      anatomical variability within the framework of computational anatomy.

PMID- 24684016
TI  - Joint modeling of imaging and genetics.
AB  - We propose a unified Bayesian framework for detecting genetic variants associated
      with a disease while exploiting image-based features as an intermediate
      phenotype. Traditionally, imaging genetics methods comprise two separate steps.
      First, image features are selected based on their relevance to the disease
      phenotype. Second, a set of genetic variants are identified to explain the
      selected features. In contrast, our method performs these tasks simultaneously to
      ultimately assign probabilistic measures of relevance to both genetic and imaging
      markers. We derive an efficient approximate inference algorithm that handles high
      dimensionality of imaging genetic data. We evaluate the algorithm on synthetic
      data and show that it outperforms traditional models. We also illustrate the
      application of the method on ADNI data.

PMID- 24684017
TI  - Eyes on Africa.

PMID- 24684018
TI  - Settlements and separation in the West Bank: future implications for health.

PMID- 24684019
TI  - The Palestinian territories: barriers to healthcare and medical education and the
      strategic role of distance-learning partnerships in education systems
      strengthening.

PMID- 24684020
TI  - Health in fragile states.

PMID- 24684021
TI  - The most fragile state: healthcare in Somalia.

PMID- 24684022
TI  - Global health diplomacy investments in Afghanistan: adaptations and outcomes of
      global fund malaria programs.
AB  - BACKGROUND: Global health programmes require extensive adaptation for
      implementation in conflict and post-conflict settings. Without such adaptations,
      both implementation success and diplomatic, international relations and other
      indirect outcomes may be threatened. Conversely, diplomatic successes may be made
      through flexible and responsive programmes. We examine adaptations and associated
      outcomes for malaria treatment and prevention programmes in Afghanistan. METHODS:
      In conjunction with the completion of monitoring and evaluation activities for
      the Global Fund to Fight AIDS, Tuberculosis and Malaria, we reviewed adaptations
      to the structure, design, selection, content and delivery of malaria-related
      interventions in Afghanistan. Interviews were conducted with programme
      implementers, service delivery providers, government representatives and local
      stakeholders, and site visits to service delivery points were completed.
      FINDINGS: Programmes for malaria treatment and prevention require a range of
      adaptations for successful implementation in Afghanistan. These include (1)
      amendment of educational materials for rural populations, (2) religious awareness
      in gender groupings for health educational interventions, (3) recruitment of
      local staff, educated in languages and customs, for both quality assurance and
      service delivery, (4) alignment with diplomatic principles and, thereby,
      avoidance of confusion with broader strategic and military initiatives and (5)
      amendments to programme 'branding' procedures. The absence of provision for these
      adaptations made service delivery excessively challenging and increased the risk
      of tension between narrow programmatic and broader diplomatic goals. Conversely,
      adapted global health programmes displayed a unique capacity to access
      potentially extremist populations and groups in remote regions otherwise isolated
      from international activities. CONCLUSIONS: A range of diplomatic considerations
      when delivering global health programmes in conflict and post-conflict settings
      are required in order to ensure that health gains are not offset by broader
      international relations losses through challenges to local cultural, religious
      and social norms, as well as in order to ensure the security of programme staff.
      Conversely, when global health programmes are delivered with international
      relations considerations in mind, they have the potential to generate
      unquantified diplomatic outcomes.

PMID- 24684023
TI  - Design and pilot implementation of an evaluation tool assessing professionalism,
      communication and collaboration during a unique global health elective.
AB  - BACKGROUND: Global health electives (GHEs) allow medical students to experience
      different health systems, but there are few instruments to assess performance,
      prompting us to adapt and pilot such an instrument. METHODS: A tool to evaluate
      professionalism, communication and collaboration was developed and piloted on GHE
      students. The main outcome measure was Faculty assessment of students, but peer
      assessment and self-assessment were also performed and semi-structured interviews
      with students were used for corroboration. The 31 items were rated using a Likert
      scale and marks before and after the GHE were compared. RESULTS: The tool was
      sensitive to change. Students improved in each competency, the greatest change
      being in collaboration, which moved from 4.5/7 to 5.44/7. Qualitative analyses
      supported observed changes. CONCLUSIONS: Our tool, adapted from accreditation
      bodies' requirements, appeared to be able to discern changes in acquisition of
      skills in several important competencies in medical students participating in a
      GHE.

PMID- 24684024
TI  - Eye injuries caused by shotgun and air-rifles treated at the University Eye
      Clinic in Belgrade 2000-2009.
AB  - INTRODUCTION: Eye injuries caused by shotgun buckshot or air-rifle bullets are
      not common but are very severe, causing blindness of the injured eye. OBJECTIVE:
      By comparison of different parameters, to determine which of these two types of
      injuries have more serious final effect on vision. METHODS: A retrospective
      comparative analysis of patients with shotgun and air-rifle injuries, treated in
      the period 2000-2009 at the University Eye Clinic in Belgrade was carried out,
      with patients being divided in two groups depending of the type of the weapon.
      Age of patients, occupation, days in the week and part of the day when the
      accidents happened, presence of the retained foreign body, as well as the visual
      acuity on admission and final visual outcome were reviewed and analyzed. RESULTS:
      There were 16 shotgun and 5 air-rifle injuries. Mean age of patients injured by
      shotgun was 45.5 +/- 11.9 years, while those injured by air-rifle bullets were
      only 15.0 +/- 1.0 years old. Shotgun accidents happened in hunters, on weekends,
      in the morning, while air-rifle accidents were typical for pupils, on working
      days, in the afternoon. Final visual acuity following buckshot injuries was: NLP
      in 6 (37.5%), less than 0.1 in 6 (37.5%) and normal (1.0) in 4 (25%) patients.
      Out of patients hit by air-rifle bullet, no light perception (NLP) was documented
      in 4 (80%) while visual acuity remained normal in one patient. CONCLUSION: All
      injuries by shotgun and air-rifle are very serious, ending in loss of vision in
      high percent of cases. Prevention is essential.

PMID- 24684025
TI  - [Clinical and microbiological effects of the initial periodontal therapy].
AB  - INTRODUCTION: Periodontitis is a destructive inflammatory disease of the tooth
      supporting tissues, primarily caused by Gram-negative microorganisms. Thus, the
      primary objective of cause-related initial periodontal therapy is disruption and
      removal of the subgingival biofilm. OBJECTIVE: The aim of this study was to
      evaluate the clinical and microbiological effects of the initial therapy in
      patients diagnosed with chronic periodontitis. METHODS: Forty patients with
      chronic periodontitis were included in the study. As a part of the clinical
      assessment undertaken prior to the initial therapy, as well as one month and
      three months post-therapy, plaque index, gingival index, papilla bleeding index,
      probing pocket depth and clinical attachment level were recorded. Microbiological
      testing was performed prior to the initial therapy and three months after
      therapy. Polymerase chain reaction assays were used to determine the presence of
      Porphyromonas gingivalis, Tannerella forsythensis, Prevotella intermedia and
      Aggregatibacter actinomycetemcomitans. RESULTS: All clinical parameters were
      significantly reduced after therapy. The prevalence of Aggregatibacter
      actinomycetemcomitans was reduced by 22.5%, which was a statistically significant
      decrease compared to the baseline. The prevalence of Porphyromonas gingivalis,
      Tannerella forsythensis and Prevotella intermedia tended to decrease after
      therapy; however, the difference did not reach statistical significance.
      CONCLUSION: The results of the present study demonstrated the beneficial effects
      of the initial periodontal therapy on both the clinical and microbiological
      parameters.

PMID- 24684026
TI  - Balloon valvuloplasty as a treatment of congenital aortic stenosis in children
      and adolescents.
AB  - INTRODUCTION: Balloon valvuloplasty (BVP) is one of the primary therapies for
      congenital aortic stenosis in children and adolescents. The aim of this
      interventional procedure is to gain time before possible surgical therapy (aortic
      valve replacement) until adulthood. OBJECTIVE: The aim of this study was to
      evaluate the efficacy, safety and mid-term results oftranscatheter BVP in
      children and adolescent in our Center. METHODS: From 2004 to 2011, 50 patients,
      aged 18 days to 18 years (mean 6.3 years) underwent BVP. Retrospective analysis
      of the echocardiographic and hemodynamic parameters were performed before and
      after procedure, especially peak pressure gradient (PG) across the aortic valve,
      semiquantification of the aortic regurgitation (AR) after the BVP as well as the
      left ventricle dimensions and functions. RESULTS: The mean peak PG in the whole
      group decreased from 74.80 +/- 27.72 mm Hg to 27.86 +/- 3.04 mm Hg (p < 0.001)
      after BVP. In 39 patients (78%), residual PG was lower than 30 mm Hg just after
      dilation. At the end of follow-up period, 25 patients (50%) had PG above 50 mm
      Hg, measured by Doppler technique, and four of them underwent re-dilation. Eight
      patients (16%) had severe AR. During the follow-up period (12-80 months, mean 51
      months), six patients (12%) were referred to cardiac surgeons for aortic valve
      replacement or Ross procedure. CONCLUSIONS: This retrospective study analyzes our
      first experience of BVP as primary therapy of the congenital aortic stenosis. The
      results confirmed that BVP effectively postponed the need for surgery in children
      and adolescents toward the adulthood.

PMID- 24684027
TI  - Changing trends in incidence of lung cancer by histological type in Montenegro.
AB  - INTRODUCTION: Lung cancer is one of the most common malignant neoplasms, as well
      as the most common cause of death cancer. Most lung cancers are squamous cell
      carcinomas, small cell carcinomas or adenocarcinomas. OBJECTIVE: Examining
      changes in trends of lung cancer incidence in Montenegro by histological type
      during a 15-year period, from 1997 to 2011. METHODS: During the study period,
      histopathological confirmation was obtained for all primary lung cancer cases in
      the only hospital for lung diseases in the country. Based on the data from
      medical records, patients were classified by time period, sex, age groups and
      smoking history. Descriptive method was used. RESULTS: Ratio between incidences
      of adenocarcinoma and squamous cell carcinoma changes in males, with a
      significant increase in the incidence rate of adenocarcinoma and drop in the rate
      of squamous cell carcinoma (p < 0.001). In addition, statistically significant (p
      < 0.05) decrease in the incidence of NSCLC (non-small cell lung cancer) and an
      increase in the incidence of SCLC (small cell lung cancer) was found. A
      statistically significant increase in linear trend in the incidence of small cell
      carcinoma was noted in females (p < 0.005). CONCLUSION: Incidence rates of
      adenocarcinoma and small cell carcinoma have increased during the study period.

PMID- 24684028
TI  - [Comparison of biohumoral and morphological parameters in acute pancreatitis].
AB  - INTRODUCTION: Acute pancreatitis occurs as a result of autodigestive activation
      of pancreatic proenzymes, within the parenchyma of the glands. OBJECTIVE: The
      goal of the work was to establish possible connection of etiology and severity of
      the acute pancreatitis and biohumoral parameters, ultrasound and CT. METHODS: The
      study included 273 patients with pancreatitis, classified by Ranson's score,
      according to degree of severity and etiology, whose biohumoral parameters were
      correlated with each other, and with the ultrasound and CT findings. RESULTS: The
      values of amylase and ALT were significantly higher in the severe form of
      pancreatitis and biliary etiology compared to etilic (p < 0.05).The ratio of
      AST/ALT was significantly higher in the group of etilic compared to biliary
      etiology (p < 0.05). LDH was significantly higher in the severe form group
      compared to moderate form of pancreatitis (p < 0.01). Cholesterol was
      significantly higher in the group of biliary compared to the group of etilic
      pancreatitis (p < 0.05). There was a negative low correlation between the value
      of calcium ions in the plasma and CT analysis (p = 0.05). Low degree negative
      correlation between the value of calcium ions and ultrasound analysis was
      established (p = 0.0001). CONCLUSION: There was a negative correlation between
      the level of ionized calcium in the blood and the degree of the acute
      pancreatitis by the Balthazar score. Mean value of alpha amylase, total value of
      cholesterol and ALT were significantly higher in the group of biliary compared to
      the group of etilic acute pancreatitis. The average values of the alpha amylase,
      LDH and ALT were significantly higher in the group of severe form of the acute
      pancreatitis compared to the group of moderate form. The ratio AST/ALT was
      significantly higher in the group of etilic than in the group of biliary
      pancreatitis.

PMID- 24684029
TI  - Evaluation of reversal osteofixation using K-wires in digital replantation.
AB  - INTRODUCTION: Modified, reversal technique of fixation in digital replantation
      using K-wires was analyzed. The results obtained from the standard technique and
      reversal technique of fixation using K-wires were compared. OBJECTIVE: The aim
      was to compare the results of osteofixation using K-wires in digital replantation
      when either standard or reversal, modified technique was used. METHODS: A
      retrospective study included 103 replanted fingers in 72 patients. The first
      group included standard fixation using K-wires and the second group included
      fixation using K-wires, but with a modified technique. Modification consisted of
      the opposite order of moves during the phalanges fixation compared to the
      standard technique: first, K-wire was introduced intramedullary in the proximal
      phalanx and the top of the wire was drawn out through the skin in proximal part
      of the finger or hand. Second, distal part of the wire was introduced in the
      phalanx of the amputated part of the finger intramedullary until the wire entered
      the cortex. RESULTS: Duration of bone healing after digital replantation was
      shorter in cases where reversal technique was used in comparison with standard
      technique (7.2 weeks compared to 7.5 weeks). CONCLUSION: The comparison of
      standard and reversal technique of phalangeal fixation with K-wires in digital
      replantation shows that both techniques are useful. Reversal technique expands
      the choice of operative techniques for bone fixation during the replantation. It
      shows some advantages and enables avoidance of vein injuries.

PMID- 24684030
TI  - Influence of different methods of internal bone fixation on characteristics of
      bone callus in experimental animals.
AB  - INTRODUCTION: Correct choice of osteosynthesis method is a very important factor
      in providing the optimal conditions for appropriate healing of the fracture.
      There are still disagreements about the method of stabilization of some long bone
      fractures. Critically observed, no method of fracture fixation is ideal. Each
      osteosynthesis method has both advantages and weaknesses. OBJECTIVE: The
      objective of this study was to compare the results of the experimental
      application of three different internal fixation methods: plate fixation,
      intramedullary nail fixation and self-dynamisable internal fixator (SIF).
      METHODS: A series of 30 animals were used (Lepus cuniculus) as experimental
      animals, divided into three groups of ten animals each. Femoral diaphysis of each
      animal was osteotomized and fixed with one of three implants. Ten weeks later all
      animals were sacrificed and each specimen underwent histological and
      biomechanical testing. RESULTS: Histology showed that the healing process with
      SIF was more complete and bone callus was more mature in comparison to other two
      methods. During biomechanical investigation (computerized bending stress test),
      it was documented with high statistical significance that using SIF led to
      stronger healing ten weeks after the operation. CONCLUSION: According to the
      results obtained in this study, it can be concluded that SIF is a suitable method
      for fracture treatment.

PMID- 24684031
TI  - Higher percentage of in vitro apoptotic cells at time of diagnosis in patients
      with chronic lymphocytic leukemia indicate earlier treatment requirement: ten
      years follow up.
AB  - INTRODUCTION: Chronic lymphocytic leukemia (CLL) has an extremely variable
      clinical course. Biological reasons for that wide variation in clinical course
      and survival rates in CLL patients are not fully understood. OBJECTIVE: The aim
      of the study was to evaluate the value of spontaneous apoptosis of CLL cells in
      vitro determined at presentation of disease, in prediction of treatment
      requirements and evolution of the CLL. METHODS: Malignant B cells were isolated
      from the whole blood of 30 newly diagnosed CLL patients and cultured for 24 hours
      in RPMI-1640 medium supplemented with 10% of serum obtained from the same CLL
      patient. Cells were later fixed and processed for embedding in Epon, or cell
      smears were prepared and stained with TUNEL technique. RESULTS: Ten-year follow
      up revealed that patients with lower percentage of cells in apoptosis at
      presentation of disease had significant longer time treatment initiation (log
      rank test p < 0.05). On the contrary, apoptosis of CLL cells was not shown to
      have significant impact on survival of patients (Kaplan Meier log rank test p >
      0.05). CONCLUSION: The results of this study emphasize the importance of
      apoptosis of CLL cells at the time of the initial diagnosis in pathobiology of
      this disease.

PMID- 24684032
TI  - [Examination of possible role of the chlamydial stress proteins in pathogenesis
      of ectopic pregnancy].
AB  - INTRODUCTION: Chlamydia trachomatis infections are the most prevalent bacterial
      sexually transmitted infections recognized throughout the world. In the last few
      years, several studies have indicated that predisposition of C. trachomatis to
      persist within the host cell is recognized as a major factor in the pathogenesis
      of chlamydial infection. During persistent chlamydial infection, the stress
      protein hsp60 is synthesized continually as immunopathologic antigen. Antibodies
      to hsp60 are found in women with tubal occlusion, but these antibodies are not
      detected in women with the acute C. trachomatis infection, which indicates that
      hsp60 has an important role in pathogenesis of persistant chlamydial infection.
      OBJECTIVE: The aim of this study was to determine the role of chlamydial stress
      proteins (heat shock proteins) in pathogenesis of ectopic pregnancy. METHODS: The
      study included 40 women with ectopic pregnancy (experimental group) and 34 women
      with normal pregnancy (control group). C. trachomatis was detected in
      endocervical smears by direct immunofluorescence test, while specific antibodies
      against Chlamydia spp. and against hsp60 were detected by ELISA. RESULTS: DIF
      method detected the presence of C. trachomatis in 12.5% of women with the ectopic
      pregnancy and 17.6% of women with normal pregnancy. IgG antibodies against
      Chlamydia spp. were found in 57.5% of women with the ectopic pregnancy and 26.5%
      of women with normal pregnancy. IgA antibodies were positive in 37.5% of women
      with the ectopic pregnancy and 2.9% of women with normal pregnancy. IgG
      antibodies against hsp60 were positive in 37.5% of women with the ectopic
      pregnancy and 14.7% of women with normal pregnancy. CONCLUSION: The results of
      this study have proven the correlation between the ectopic pregnancy and the
      presence of IgG antibodies to chlamydial hsp60.

PMID- 24684033
TI  - [Assessment of required resources for implementation of national breast cancer
      screening program in Serbia].
AB  - INTRODUCTION: High values of standardized mortality and morbidity rates of
      standardized cancer mortality in Serbia, especially colorectal, cervical and
      breast cancer led to creation of national programs for their early detection and
      engagement of the international support for their implementation. OBJECTIVE:
      Assessment of required resources (time, personnel, financial) to implement the
      National program for screening of breast cancer in the Republic of Serbia.
      METHODS: Three possible scenarios have been prepared (optimistic, realistic and
      pessimistic) based on the expected coverage by screening of women aged 45 to 69
      years, and time, personnel and financial feasibility estimates were made for a
      two-year screening cycle. RESULTS: Time aspect of feasibility even under
      conditions of "relaxation" of the assumption on the number of working days during
      the year did not question feasibility of any of the scenarios. Personnel
      feasibility is only possible in the pessimistic scenario, while the financial
      feasibility only makes sense in optimistic scenario as the least unfavorable
      solution due to economies of scale. CONCLUSION: Establishment of the initial base
      of skilled radiologists and radiology technicians and the system for their
      continuous medical education as well as allocation of specific MoH budget line
      for screening program expenditures, along with donated mammographs and good
      organization and coordination, may provide unobstructed implementation of the
      National program for early detection of breast cancer in the Republic of Serbia.

PMID- 24684034
TI  - Surgical treatment of intradiploic epidermoid cyst treated as depression.
AB  - INTRODUCTION: Extradural intradiploic epidermoid cysts are rare, representing
      less than 0.25% of all primary intracranial tumors. They can be neurologically
      silent and can only present psychiatric symptoms like depression, cognitive or
      personality changes. CASE OUTLINE: A 68-year-old male with two year long history
      of depressive mood, lack of motivation, helplessness, hopelessness and poor
      response to antidepressive drug therapy was described. CT scan showed a well
      defined mass in the parietal scalp with destruction of the scull. He underwent
      intracranial tumor resection. Surgical resection and cranioplasty were performed.
      Pathology confirmed intradiploic epidermoid cyst. CONCLUSION: Total removal of
      these cysts and repeated washing of the cavity with 0.9% saline may prevent
      recurrence and aseptic meningitis and may improve mental state of the patient. We
      also emphasize the need for neuroimaging studies in a patient with atypical
      changes in mental status, even without neurological signs or symptoms.

PMID- 24684035
TI  - Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple
      endocrine neoplasia type 2A mutation (codon 634).
AB  - INTRODUCTION: The multiple endocrine neoplasia type 2A (MEN 2A) syndrome,
      comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary
      hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating
      mutations of the RET (rearranged during transfection) proto-oncogene on
      chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before
      the age of 5 years) would be advantageous in limiting the potential for the
      development of MTC as well as parathyroid adenomas. CASE OUTLINE: This is a case
      report of 3-year-old boy from the MEN 2A family (the boy's father and grandmother
      and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634
      in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the
      basis of genetic information. A boy had no thyromegaly, thyroidal irregularities
      or lymphadenopathy and no abnormality on the neck ultrasound examination. The
      pathology finding of thyroid gland was negative for MTC. Two years after total
      thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement.
      His serum calcitonin level is < 2 pg/ml (normal < 13 pg/ml), has normal serum
      calcium and parathyroid hormone levels and negative urinary catecholamines. Long
      term follow-up of this patient is required to determine whether very early
      thyroidectomy improves the long-term outcome of PHPT. CONCLUSION: Children with
      familial antecedents of MEN 2A should be genetically studied for the purpose of
      determining the risk of MTC and assessing the possibilities of making
      prophylactic thyroidectomy before the age of 5 years.

PMID- 24684036
TI  - X-linked hypophosphatemic rickets: case report.
AB  - INTRODUCTION: X-linked hypophosphatemic rickets (XLHR) is a dominant inherited
      disease caused by isolated renal phosphate wasting and impairment of vitamin D
      activation. We present a girl with X-linked hypophosphatemic rickets (XLHR) as a
      consequence of de novo mutation in the PHEX gene. CASE OUTLINE: A 2.2-year-old
      girl presented with prominent lower limb rachitic deformity, waddling gait and
      disproportionate short stature (79 cm, < P5; -1,85 SD). On the basis of
      hypophosphatemia, hyperphosphaturia, high serum level of alkaline phosphatase,
      normal calcemia, 25(OH)D and PTH, as well as characteristic clinical and X-ray
      findings, diagnosis of hypophosphatemic rickets (HR) was made. Normal calciuria
      and absence of other renal tubular disorders indicated HR as a consequence of
      isolated hyperphosphaturia. The treatment (phosphate 55 mg/kg and calcitriol 35
      ng/kg per day), introduced 15 month ago, resulted in a stable normalization of
      alkaline phosphatase and phosphorus serum levels (with intact calcemia and
      calciuria), disappearance of X-ray signs of the active rickets and improvement of
      the child's longitudinal growth (0.6 cm per month). Subsequently, by detection of
      already known mutation in the PHEX gene: c.1735G>A (p.G579R) (exon 17), XLHR was
      diagnosed. Analysis of the parental PHEX gene did not show the abnormality, which
      indicated that the child's XLHR was caused by de novo mutation of this gene.
      CONCLUSION: Identification of genetic defects is exceptionally significant for
      diagnosis and differential diagnosis of hereditary HR.

PMID- 24684037
TI  - A case of human monocytic ehrlichiosis in Serbia.
AB  - INTRODUCTION: Ehrlichiosis is a bacterial zoonosis transmitted by hematophagous
      arthropods--ticks. In humans, it occurs as monocytic, granulocytic, and ewingii
      ehrlichiosis. Pathological process is based on parasitic presence of Ehrlichia
      organisms within peripheral blood cells--monocytes and granulocytes. CASE
      OUTLINE: Fifty-two year old patient was admitted to hospital due to high fever of
      over 40 degrees C that lasted two days, accompanied with chills, muscle aches,
      malaise, loss of appetite, headache, confusion, breathing difficulties, and mild
      dry cough. The history suggested tick bite that occurred seven days before the
      onset of disease. Doxycycline was introduced and administered for 14 days,
      causing the disease to subside. Indirect immunofluorescence assay was used to
      analyze three serum samples obtained from this patient for Ehrlichia chaffeensis
      antibodies, and peripheral blood smear was evaluated for the presence of
      Ehrlichia and Ehrlichia aggregation into morulae. CONCLUSION: Ehrlichiosis should
      be considered in each case where there is a history of tick bite together with
      the clinical picture (high fever, chills, muscle aches, headache, generalized
      weakness and malaise, and possible maculopapular rash). The presence of Ehrlichia
      chaffeensis antibodies was confirmed in a patient with the history of tick bite,
      appropriate clinical picture and indirect immunofluorescence assay. This
      confirmed the presence of human monocytotropic ehrlichiosis, a disease that is
      uncommonly identified in our country.

PMID- 24684038
TI  - Post-transplant lymphoproliferative disorder--case reports of three children with
      kidney transplant.
AB  - INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a
      heterogeneous group of diseases, characterized by abnormal lymphoid proliferation
      following transplantation. It is a disease of the immunosuppressed state, and its
      occurrence is mostly associated with the use of T-cell depleting agents, and also
      intensification of immunosuppressive regimens. In the majority of cases, PTLD is
      a consequence of Epstein-Barr virus (EBV) infection and is a B-cell hyperplasia
      with CD-20 positive lymphocytes. The 2008 World Health Organization
      classification for lymphoid malignancies divides PTLD into four major categories:
      early lesions, polymorphic PTLD, monomorphic PTLD and Hodgkin PTLD. The treatment
      and prognosis depend on histology. The cornerstone of PTLD therapy includes
      reduction/withdrawal of immunosuppression, monoclonal anti CD-20 antibody
      (rituximab) and chemotherapy. OUTLINE OF CASES: We reported here our experiences
      with three patients, two girls aged 7.5 and 15 and a 16-year old boy. They had
      different organ involvement: brain, combined spleen-liver and intestines,
      respectively. Even though EBV was a trigger of lymphoid proliferation as it was
      confirmed by histopathology or in cerebrospinal fluid, qualitative EBV-PCR was
      positive only in one patient at disease presentation. Reduction of
      immunosuppression therapy was applied in treatment of all three patients, while
      two of them received rituximab and ganciclovir. They had an excellent outcome
      besides many difficulties in diagnosis and management of disease. CONCLUSION:
      Qualitative EBV-PCR is not useful marker in pediatric transplant recipients. Our
      suggestion is that patients with the risk factors like T-cell depleting agents,
      immunosuppressant protocol or increasing immunosuppressive therapy and EBV miss
      match with donor must be more accurately monitored with quantitative EBV PCR.

PMID- 24684039
TI  - [Congenital pseudarthrosis of lower leg treated by almost outdated method--case
      report].
AB  - INTRODUCTION: Congenital pseudarthrosis of tibia is a rare congenital deformity
      with progressive evolution. Treatment is vague and difficult, and many methods
      have been used--from once mandatory early amputation to contemporary operative
      (Ilizarov method, free microvascular fibular graft) and adjuvant methods
      (electrostimulation, biphosphonates, bone morphogenetic protein). We present the
      usage of once popular method of homologous graft insertion and intramedullary
      fixation. CASE OUTLINE: This is a case report of male patient with pseudarthrosis
      involving both crural bones (Boyd type 5), diagnosed in neonatal age. Early
      conservative treatment was unsuccessful, so child never initiated gait. At the
      age of three and a half years, operative treatment was applied: resection of
      pseudarthrosis on both tibia and fibula, and osteoplasty of tibia using cylindric
      homologous graft and intramedullary fixation with transtarsal Steinman pin,
      followed by long leg cast immobilization. Pin was removed after ten months, and
      physical therapy was initiated 1.5 year after surgery, with initial to partial
      weight bearing and short leg cast throughout another year. Two and a half years
      after surgery complete union of graft was documented, and then full weight
      bearing was allowed. At final visit, five years and three months after surgery,
      shin axis was correct, leg lengths were equal, and child had normal walk with
      full range of motion. X-ray showed complete union of both tibia and fibula.
      CONCLUSION: Despite bad prognostic factors (young age, severe deformity),
      utilization of obsolete and almost forgotten treatment methods can provide
      excellent result.

PMID- 24684040
TI  - [Black esophagus--case report].
AB  - INTRODUCTION: Diseases of the gastrointestinal system, and especially diseases of
      esophagus, are a rare cause of sudden unexpected death in any age group. Black
      esophagus is an acute necrotizing inflammation of the mucosa of the lower parts
      of esophagus, diffusely affecting its entire circumference. This inflammation
      could be a source of profuse bleeding and cause sudden unexpected death. CASE
      OUTLINE: A case of 76-year-old male was presented herein. He has been treated for
      hypertension and diabetes for several years. As a consequence of stroke, which
      happened several months prior to death, he had been hemiplegic and immobilized.
      He died in hospital, suddenly and unexpectedly. The autopsy showed the acute
      necrotizing esophagitis, as well as the acute gastric and duodenal erosions of
      mucosa. These were the causes of fatal blood loss. CONCLUSION: Acute necrotizing
      esophagitis should be recognized during autopsy and related to the immediate
      cause of death as well as to concomitant diseases of other organs, which either
      potentiate or facilitate presentation of this disease.

PMID- 24684042
TI  - Current concepts of pathophysiology, epidemiology and classification of pruritus.
AB  - Discovery of pruritus-specific mediators and receptors facilitated the
      neurobiological concept of pruritus: itch-specific (histamine-dependent and
      histamine-independent C-fibers); itch-specific receptors on cutaneous and spinal
      neurons; "dialogue" between the pruritus-specific neurons and cells in the skin;
      peripheral and central mediation of pruritus; functional "pruritus-specific
      matrix" in the brain with a role of pruritus center. In 10%-50% of persons
      without skin diseases, pruritus is considered the manifestation of a systemic
      disorder. Identification of pruritus within autoimmune and inflammatory diseases
      in dermatology is based on the clinical picture and nature of the underlying
      disease, implying the development of pruritus on primarily and/or secondarily
      inflamed skin. In the internal medicine, pruritus commonly presents on primarily
      non-inflamed skin., involvement of the skin and gastrointestinal tract are two
      independent risk factors of pruritus in systemic sclerosis, and of anal/vulvar
      pruritus. Classification combines etiological and clinical criteria and should be
      considered the only segment of a comprehensive approach to pruritus of unknown
      origin.

PMID- 24684041
TI  - [The application of air abrasion in dentistry].
AB  - One of the main objectives of contemporary dentistry is to preserve healthy tooth
      structure by applying techniques of noninvasive treatment. Air abrasion is a
      minimally invasive nonmechanical technique of tooth preparation that uses kinetic
      energy to remove carious tooth structure. A powerful narrow stream of moving
      aluminum-oxide particles hit the tooth surface and they abrade it without heat,
      vibration or noise. Variables that affect speed of cutting include air pressure,
      particle size, powder flow, tip's size, angle and distance from the tooth. It has
      been proposed that air abrasion can be used to diagnose early occlusal-surface
      lesions and treat them with minimal tooth preparation using magnifier. Reported
      advantages of air abrasion include reduced noise, vibration and sensitivity. Air
      abrasion cavity preparations have more rounded internal contours than those
      prepared with straight burs. This may increase the longevity of placed
      restorations because it reduces the incidence of fractures and a consequence of
      decreased internal stresses. However, air abrasion cannot be used for all
      patients, i.e. in cases involving severe dust allergy, asthma, chronic
      obstructive lung disease, recent extraction or other oral surgery, open wounds,
      advanced periodontal disease, recent placement of orthodontic appliances and oral
      abrasions, or subgingival caries removal. Many of these conditions increase the
      risk of air embolism in the oral soft tissues. Dust control is a challenge, and
      it necessitates the use of rubber dam, high-volume evacuation, protective masks
      and safety eyewear for both the patient and the therapist.

PMID- 24684043
TI  - Renal hypertension and cardiovascular disorder in children with chronic kidney
      disease.
AB  - Renal hypertension is one of the earliest and the most prevalent complications of
      pediatric chronic kidney disease (CKD). Among renal patients, hypertension is
      frequently underdiagnosed and undertreated. For casual blood pressure
      measurement, the best method is auscultatory, while for ambulatory blood pressure
      measurement, oscillometric method is the most commonly used. Both casual and
      ambulatory blood pressure measurement provide more powerful means of diagnosing
      hypertension. Masked hypertension is a condition in which casual blood pressure
      is normal but ambulatory blood pressure is elevated. The risk of cardiovascular
      morbidity and mortality is higher with masked hypertension as compared to the
      controls. Children and adolescents with CKD are at high risk of cardiovascular
      disease that has been established as the leading cause of death in patients with
      end stage renal disease. Left ventricular hypertrophy remains the most thoroughly
      documented form of end-organ damage caused by hypertension in children and
      adolescents with CKD. Based on clear evidence on the correlation between blood
      pressure and cardiovascular morbidity, mortality, and renal function, renal
      hypertension must be aggressively treated. Target blood pressure for patients
      with renal hypertension should be at low normal values: < 75 percentile for
      patients without proteinuria and <50 percentile for patients with proteinuria.
      Renin-angiotensin system antagonists are considered the first choice
      pharmacological option in hypertensive CKD 2-4 patients while the management of
      volume overload is the most important in dialysis patients. Successful
      transplantation can eliminate or significantly improve uremia-related
      cardiovascular risk factors and increase predicted life expectancy.

PMID- 24684044
TI  - [Uterine myomas in pregnancy, childbirth and puerperium].
AB  - Fibroids are the most common benign tumors of the genital organs of women in
      reproductive age. Achieving reproductive function later in life, with more
      frequent use of assisted reproductive technologies, leads to an increased number
      of pregnancies complicated with fibroids. Their size may change during pregnancy,
      but the changes are mostly individual. Most fibroids stop growing or decline
      during the puerperium. The effect of fibroids on pregnancy depends on their
      number, size and location. The mechanisms bringing about perinatal complications
      are not fully understood. Fibroids during pregnancy can cause many perinatal
      complications, such as bleeding in pregnancy, miscarriage, pain due to red
      degeneration, malpresentation, preterm labor, premature rupture of membranes,
      placental abruption and obstruction of delivery and are associated with higher
      incidence of cesarean section, operative vaginal delivery, uterine atony and
      postpartum hemorrhage. Postpartum hysterectomy in these women is also more likely
      than in general population. Postpartum infections are more common in patients
      with fibroids, and myomas may also cause retained placenta. The most common cause
      of neonatal morbidity is prematurity, due to pregnancy ending in an earlier
      gestational age. Monitoring of pregnancies complicated with fibroids is
      essentially indistinguishable from monitoring normal pregnancies. Therapy
      includes only bed rest and observation, symptomatic therapy in case of pain and
      intensive fetal surveillance, and surgery in the acute situations.

PMID- 24684045
TI  - Nutrition in pregnancy: basic principles and recommendations.
AB  - Healthy diet in pregnancy should guarantee proper fetal growth and development,
      maintain (and promote) maternal health and enable lactation. Nutritional
      counseling and interventions need to be an integral part of antenatal care and
      continue during pregnancy in order to reduce the risk of maternal, fetal and
      neonatal complications, as well as the short- and long-term adverse outcomes.
      Adverse pregnancy outcomes are more common in women who begin the gestation as
      undernourished or obese in comparison to pregnant women whose weight is within
      normal ranges. Increased nutritional and energy needs in pregnancy are met
      through numerous metabolic adaptations; pregnancy is successfully achieved within
      wide range of variations in energy supply and weight gain. However, if nutrient
      restriction exceeds the limits of adaptive responses, evidence indicates that
      fetus will develop the alternative metabolic competence that might emerge as a
      disease (type 2 diabetes, hypertension, coronary heart disease and stroke) in
      adult life.

PMID- 24684046
TI  - [Pioneers of invasive cardiovascular medicine--Charles Theodore Dotter and
      colleagues: short historical review].
AB  - Within modern medicine at the beginning of 21st century, we are witnessing a
      revolutionary development of the invasive diagnostics and therapy of
      cardiovascular system diseases. With the discovery of X-rays at the end of 19th
      century by Wilhelm Roentgen, it is appropriate to reflect on the gifted
      individuals whose efforts drastically altered radiology and cardiology. The early
      techniques used in peripheral percutaneous transluminal angioplasty form the
      basis for subsequent percutaneous intervention both in the peripheral and
      coronary arteries and are largely the contribution of Charles Dotter. The main
      goal of his work was the use of catheters for diagnosis and treatment in an
      attempt to replace the scalpel. He was 20 years ahead of his time, especially
      with percutaneous transluminal angioplasty. The first percutaneous transluminal
      angioplasty marked a new era in the treatment of peripheral atherosclerotic
      lesions. This practical genius dedicated his considerable energy to the belief
      that there is always a better way to treat disease. His personal contributions to
      clinical medicine, research, and teaching have saved millions of limbs and lives
      all over the world. European physicians, who were more open to unproven
      techniques, almost immediately embraced percutaneous transluminal angioplasty.
      Without the contribution and help of his colleagues, Forssmann, Sones and
      Gruntzig, all of them pioneers, nothing would be done.They were all ahead of
      there time and opened completely new chapter in medicine.

PMID- 24684047
TI  - Morphological and ultrastructural redescription of Chloromyxum leydigi
      Mingazzini, 1890 (Myxozoa: Myxosporea), type species of the genus, infecting the
      gall bladder of the marine cartilaginous fish Torpedo marmorata Risso
      (Chondrichthyes: Torpedinidae), from the Portuguese Atlantic Coast.
AB  - Chloromyxum leydigi Mingazzini, 1890, the type species of Chloromyxum Mingazzini,
      1890, is redescribed based on material found in the gall bladder of the
      cartilaginous fish Torpedo marmorata Risso collected from the Portuguese Atlantic
      coast and its sporogonic development is described. Plasmodia and mature spores
      were floating free in the bile. Plasmodia are polysporic and highly polymorphic
      in shape and organization. Mature spores are spherical to subspherical with a
      pointed anterior end, measuring 12.3 +/- 0.5 microm in length and 9.0 +/- 0.5
      microm in width. The spore wall is composed of two asymmetric shell valves, each
      bearing 4-5 elevated surface ridges. A bundle of 40-50 tapering caudal filaments
      extends from the basal portion of the shell valves. Four pyriform equal-sized
      polar capsules, measuring about 5.3 x 3.2 microm, are observed at the same level
      in the anterior pole of the spores, each containing a polar filament coiled in 8
      9 (rarely 10) turns. Spore morphology, tissue tropism, host species and sequences
      of the SSU rRNA gene supported species identification. Since its discovery, this
      species has been dubiously reported from several cartilaginous hosts, namely due
      to the poor description of its features.

PMID- 24684048
TI  - Description of Sarcocystis lari sp. n. (Apicomplexa: Sarcocystidae) from the
      great black-backed gull, Larus marinus (Charadriiformes: Laridae), on the basis
      of cyst morphology and molecular data.
AB  - A morphological type of Sarcocystis cysts found in one of two examined great
      black-backed gull, Larus marinus (Linnaeus) (Laridae), is considered to represent
      a new species for which the name Sarcocystis lari sp. n. is proposed and its
      description is provided. The cysts are ribbon-shaped, very long (the largest
      fragment found was 6 mm long) and relatively narrow (up to 75 microm). Under a
      light microscope the cyst wall reaches up to 1 microm and seems to be smooth.
      Using a computerized image analysis system, knolls, which resemble protrusions on
      the wall surface, are visible. Lancet-shaped cystozoites measure in average 6.9 x
      1.4 microm (range 6.3-7.9 microm x 1.2-1.5 microm) in length. Observed using
      Transmission electron microscopy (TEM), the cyst wall is wavy and measures up to
      1.2 microm in thickness. The parasitophorous vacuolar membrane has regularly
      arranged small invaginations. Cyst content is divided into large chambers by
      septa. Sarcocystis lari sp. n. has type-1 tissue cyst wall and is morphologically
      indistinguishable from other bird Sarcocystis species characterized by the same
      type of the wall. On the basis of 18S rRNA gene, 28S rRNA gene and ITS-1 region
      sequences, S. lari is a genetically distinct species, being most closely related
      to avian Sarcocystis species whose definitive hosts are predatory birds.

PMID- 24684049
TI  - The first report of Toxoplasma gondii antibodies in free-living European bison
      (Bison bonasus bonasus Linnaeus).
AB  - Toxoplasma gondii Nicolle et Manceaux, 1908 is an apicomplexan parasite with a
      worldwide distribution. It is of great medical and veterinary importance because
      it may cause abortion or congenital disease in its intermediate hosts, including
      man. The European bison, the largest herbivorous animal in Europe, is a species
      that has been saved from extinction. Twenty-four of 95 examined sera of the
      European bison (Bison bonasus bonasus) from the Bialowieza Forest, Poland
      collected from 2008 to 2011 were found to be positive for the presence of T.
      gondii-specific IgG antibodies using a direct agglutination test, with the
      antibody titre in positive animals ranging from 40 to 18000. Statistically
      significant differences were observed only between years of sample collection.
      This is the first report on T. gondii in lowland European bison living in the
      natural environment.

PMID- 24684050
TI  - A review of the genus Paramoniezia Maplestone et Southwell, 1923 (Cestoda:
      Anoplocephalidae), with a new genus, Phascolocestus, from wombats (Marsupialia)
      and redescriptions of Moniezia mettami Baylis, 1934 and Moniezia phacochoeri
      (Baylis, 1927) comb. n. from African warthogs (Artiodactyla).
AB  - Paramoniezia suis Maplestone et Southwell, 1923 is redescribed from the type and
      only specimen, and is considered to be a genus inquirendum and species
      inquirenda, possibly based on a host misidentification. Paramoniezia phacochoeri
      Baylis, 1927 is redescribed from new material from Phacochoerus africanus
      (Gmelin) from South Africa and is transferred to Moniezia Blanchard. 1891 as M.
      phacochoeri (Baylis, 1927) comb. n. A redescription of M. mettami Baylis, 1934,
      also from Ph. africanus, establishes the independence of the two congeneric
      species parasitizing warthogs. A new genus, Phascolocestus, is erected for
      Paramoniezia johnstoni Beveridge, 1976 from vombatid marsupials as Phascolocestus
      johnstoni (Beveridge, 1976) comb. n., and additional host and distributional data
      are provided for this species.

PMID- 24684051
TI  - Detection of antibodies to Neospora caninum in moose (Alces alces): the first
      report in Europe.
AB  - Neospora caninum Dubey, Carpenter, Speer, Topper et Uggla, 1988 is a protozoan
      parasite originally reported as a major cause of bovine abortions worldwide. It
      is documented that the parasite is widely spread among non-carnivorous cervids.
      The purpose of this study was to investigate the seroprevalence of N. caninum in
      moose (Alces alces Linnaeus). Blood samples collected in 2010 and 2012 in the
      northeastern Poland were tested for antibodies to N. caninum by agglutination
      test (NAT), a commercial competitive screening enzyme-linked immunosorbent assay
      (cELISA) and enzyme-linked immunoassay (ELISA). Sera that gave a positive result
      were further investigated by western blot (WB) analysis to verify the presence of
      antibodies. Antibodies to N. caninum were detected in one of seven moose. The
      antibody titer was confirmed by NAT (1 : 1 280), cELISA (I = 91%) and ELISA (OD =
      0.736). The main immunodominant antigens detected by WB were 120, 70, 55, 35 and
      16 kDa proteins. This is the first evidence of N. caninum seropositivity in moose
      living in a natural environment in Europe.

PMID- 24684052
TI  - Philometrid nematodes (Philometridae) from marine fishes off the northern coast
      of Australia, including three new species.
AB  - Based on light and scanning electron microscopical studies, the following nine
      species of Philometridae (Nemaoda: Dracunculoidea) are described from female
      worms parasitizing marine perciform fishes belonging to six families off the
      northern coast Australia (near Darwin): Philometra australiensis sp. n. from the
      swimbladder of the king threadfin Polydactylus macrochir (Gunther) (Polynemidae);
      P. epinepheli Dewi et Palm, 2013 from the operculum of the orange-spotted grouper
      Epinephelus coioides (Hamilton) (Serranidae); Philometra johnii Moravec et Ali,
      2013 from the gonad of the croaker Johnius sp. (Sciaenidae); P. macrochiri sp. n.
      from the sensory fin of P. macrochir; P. zabidii sp. n. from the ovary of the
      ninespine batfish Zabidius novemaculatus (McCulloch) (Ephippidae); Philometra sp.
      1 and Philometra sp. 2 from the ovary of the Spanish flag snapper Lutjanus
      carponotatus (Richardson) (Lutjanidae) and the silver grunt Pomadasys argenteus
      (Forsskal) (Haemulidae), respectively; Philometroides eleutheronemae Moravec et
      Manoharan, 2013 from the ovary of the fourfinger threadfin Eleutheronema
      tetradactylum (Shaw) (Polynemidae); and Spirophilometra endangae Dewi et Palm,
      2013 from the pectoral fins of E. coioides. The new species P. australiensis is
      characterized mainly by the structure of the cephalic end, 14 minute cephalic
      papillae, absence of caudal projections and body length of gravid female (67 mm),
      P. macrochiri by the presence of a conspicuously large anterior oesophageal bulb,
      14 very small cephalic papillae and the truncated posterior end of body without
      any caudal projections, whereas P. zabidii is characterized by the presence of
      distinct caudal projections, the number (14) and larger size and arrangement of
      cephalic papillae, a poorly developed anterior oesophageal inflation, the body
      length (114 mm) and the host family (Ephippidae). All above-mentioned species
      were recorded from Australian waters for the first time.

PMID- 24684053
TI  - A new species of Comephoronema (Nematoda: Cystidicolidae) from the squirrelfish
      Holocentrus adscensionis (Beryciformes: Holocentridae) off Brazil.
AB  - A new nematode species, Comephoronema multipapillatum sp. n. (Cystidicolidae), is
      described from the anterior intestine and caecum of the squirrelfish Holocentrus
      adscensionis (Osbeck) (Beryciformes: Holocentridae) collected in Angra dos Reis,
      State of Rio de Janeiro, offshore Brazil. The new species was placed in
      Comephoronema Layman, 1933 by having an oval oral aperture, four submedian labia,
      four bilobed submedian sublabia, two narrow lateral pseudolabia and four single
      cephalic papillae, but mainly by numerous precloacal papillae in males (more than
      six pairs), in which it differs from species of the otherwise morphologically
      similar genus Ascarophis van Beneden, 1871. Comephoronema multipapillatum sp. n.
      can be easily distinguished from other congeners based on the high number of
      precloacal papillae in males (18 pairs + one unpaired) and also by the bidentate
      plate structure on the inner margin of pseudolabia, mature eggs with two long
      filaments on a single pole, body length of male (9.4-11.5 mm) and female (10.2
      19.9 mm), left spicule size (222-278 microm) and length ratio of spicules (1 :
      2.2-2.8). This is the fifth nominal species of Comephoronema, the first nematode
      registered parasitizing H. adscensionis and the first species of the genus in the
      Neotropical part of the Atlantic Ocean.

PMID- 24684054
TI  - Capillostrongyloides morae sp. n. (Nematoda: Capillariidae) from deep-sea fish
      (Teleostei, Moridae) in the western Mediterranean Sea.
AB  - A new capillariid nematode, Capillostrongyloides morae sp. n., is described from
      specimens collected from the stomach and intestine of the common mora, Mora moro
      (Risso), and the Mediterranean codling, Lepidion lepidion (Risso) (both
      Gadiformes, Moridae), off the Mediterranean coasts of Spain. The new species
      shows similar morphological features as other congeneric species occurring in
      freshwater and marine fishes, but it differs in the length of the body and
      spicules, the size of the caudal bursa, and the presence of an elevated anterior
      vulvar lip. Capillostrongyloides morae sp. n. is the second species within the
      genus for which the presence of a stylet is reported, and the first one in which
      this structure along with the distribution of cephalic papillae and oral
      structures (e.g. lips and lobes) are clearly shown by using scanning electron
      microscopy.

PMID- 24684055
TI  - Subulura halli (Ascaridida: Subuluridae) from the endangered great bustard Otis
      tarda Linnaeus (Aves: Gruiformes) in China.
AB  - Subulurid nematodes identified as Subulura halli Barreto, 1918 were collected
      from the endangered bird Otis tarda Linnaeus (Gruiformes: Otididae) in China. A
      detailed redescription of the hitherto poorly known species is presented using
      both light and, for the first time, scanning electron microscopy. Previously
      unreported and erroneous morphological features of taxonomic significance are
      revealed. This species can be readily distinguished from its congeners by the
      relatively long oesophagus (1.47-1.92 mm long, representing 10.6-16.9% of body
      length), the number and arrangement of male caudal papillae (11 pairs in total,
      arranged as five pairs of precloacal and six pairs of postcloacal papillae), the
      equal length of spicules (1.35-1.52 mm long, representing 10.7-13.7% of body
      length) and the presence of a small medioventral, precloacal papilla in the male.

PMID- 24684056
TI  - Cryopreservation of roe deer abomasal nematodes for morphological identification.
AB  - Conventional methods to preserve adult nematodes for taxonomic purposes involve
      the use of fixative or clearing solutions (alcohol, formaldehyde, AFA and
      lactophenol), which cause morphological alterations and are toxic. The aim of
      this study is to propose an alternative method based on glycerol-cryopreservation
      of nematodes for their subsequent identification. Adults of trichostrongylid
      nematodes from the abomasum of roe deer (Capreolus capreolus Linnaeus) were
      glycerol-cryopreserved and compared with those fixed in formaldehyde, fresh and
      frozen without cryoprotectans. Morphology, transparency and elasticity of the
      anterior and posterior portion of male nematodes were compared, especially the
      caudal cuticular bursa and genital accessories. The method presented is quick and
      easy to use, and the quality of nematode specimens is better than that of
      nematodes fixed by previously used fixatives. Moreover, glycerol cryopreserved
      nematodes can be stored for a long time at -20 degrees C in perfect condition and
      they could be suitable for further analyses, such as histological or
      ultrastructural examinations.

PMID- 24684057
TI  - Host specificity and metamorphosis of the glochidium of the freshwater mussel
      Unio tumidiformis (Bivalvia: Unionidae).
AB  - The glochidium larvae of freshwater mussels of the family Unionidae need to find
      suitable hosts to attach themselves and metamorphose into free-living juveniles.
      The specificity of the host-parasite relationship was investigated for the
      Iberian Unio tumidiformis Castro, 1885 by means of experimental infections and
      also by analyzing naturally infected fish. The process of encapsulation of
      glochidia was studied using scanning electron microscopy. Unio tumidiformis has
      proven to be an unusual host-specific unionid mussel, apparently parasitizing
      only fish of the genus Squalius Bonaparte, 1837. Successful encapsulation or
      complete metamorphosis was observed in five fish taxa: S. aradensis (Coelho,
      Bogutskaya, Rodrigues et Collares-Pereira), S. caroliterti (Doadrio), S.
      pyrenaicus (Gunther), S. torgalensis (Coelho, Bogutskaya, Rodrigues et Collares
      Pereira) and S. alburnoides (Steindachner) complex (only for the nuclear hybrids
      with at least one copy of the S. pyrenaicus genome). Complete metamorphose was
      achieved in 6 to 14 days at mean temperatures ranging from 21.8 to 26.1 degrees
      C. The current study provides support for cell migration being the main force of
      cyst formation and shows the influence of potential host's genome in response to
      the infection process to determine the success of the metamorphosis.

PMID- 24684058
TI  - A new species of the feather mite genus Rhinozachvatkinia (Acari: Avenzoariidae)
      from Calonectris shearwaters (Procellariiformes: Procellariidae): integrating
      morphological descriptions with DNA barcode data.
AB  - Rhinozachvatkinia calonectris sp. n., a new species of the feather mite genus
      Rhinozachvatkinia Mironov, 1989 (Avenzoariidae: Bonnetellinae), is described from
      two species of shearwaters in the North-East of the Atlantic Ocean, Calonectris
      edwardsii (Oustalet) (type host) and Calonectris borealis (Cory)
      (Procellariiformes: Procellariidae). We completed the morphological description
      of this new feather mite species with sequence data on the mitochondrial
      cytochrome c oxidase subunit I gene fragment (COI). The full generic status of
      Rhinozachvatkinia, originally established as a subgenus of Zachvatkinia Dubinin,
      1949, is formally fixed and its systematic relationships are briefly discussed.

PMID- 24684059
TI  - [Morphological changes in retina and optic nerve head in patients with Leber's
      hereditary optic neuropathy].
AB  - OBJECTIVE: To study morphological changes of the macula and the peripapillary
      nerve fiber layer in patients with Leber's hereditary optic neuropathy (LHON).
      MATERIAL AND METHODS: A total of 21 patients (40 eyes) with LHON and 17 healthy
      volunteers (33 eyes) of the control group were assessed. Optical coherence
      tomography (OCT) on RTVue-100 for retina and optic nerve head assessment was
      performed in all cases. RESULTS: Thinning of the inner retinal layers in nasal
      and inferior parafoveal sectors takes place in the early acute period of the
      disease and then spreads to the rest of the macular area. The retinal nerve fiber
      layer (RNFL) in the early acute period is of more thickness in temporal,
      inferior, and superior sectors in comparison to controls, but later gradually
      becomes thinner, especially in the temporal sector. In the late period
      significant peripapillary RNFL thinning is present in all sectors. CONCLUSION:
      OCT reveals certain structural changes in the macular area and the peripapillary
      RNFL that are characteristic of Leber's hereditary optic neuropathy and together
      with clinical presentation can substantiate the diagnosis.

PMID- 24684060
TI  - [Morphological characteristics of the macula in patients with retinal vein
      occlusion before and after the treatment: preliminary results].
AB  - The article presents examination results of 26 patients with macular edema (ME)
      due to retinal vein occlusion (RVO) before and 1 month after an intravitreal
      injection of ranibizumab (Lucentis). Besides routine assessment, retinal spectral
      domain optical coherent tomography (OCT) was performed in all cases. In
      accordance with derived OCT patterns of macular edema the patients were devided
      into two groups: swelling of the inner and outer retinal layers with serous
      detachment of neuroepithelium (group 1) and intraretinal edema with pseudocysts
      (group 2). It is shown that initial OCT features of retina in patients with ME
      due to RVO are prognostic for treatment results (serous retinal detachment may
      serve as a preventing factor of photoreceptor damage) and that visual improvement
      in patients with ME and serous detachment of neuroepithelium anticipates
      morphological changes.

PMID- 24684061
TI  - [Retinoblastoma and "pseudoretinoblastoma" in children: clinical, tomographic and
      serological features].
AB  - Clinical and tomographic features of retinoblastoma and posterior pole
      inflammatory granuloma ("pseudoretinoblastoma") as well as infectious status in
      both conditions were assessed in 16 children (32 eyes). The data obtained allow
      differential diagnosis of neoplastic and inflammatory processes and further
      adequate treatment.

PMID- 24684062
TI  - [Transciliary vitreous drainage as a treatment method for hypertensive pain
      syndrome in terminal glaucoma].
AB  - OBJECTIVE: To develop a surgical technique based on transciliary vitreous
      drainage and aimed at pain elimination in refractory glaucoma. MATERIAL AND
      METHODS: A total of 33 eyes with terminal painful glaucoma were assessed and
      surgically treated. RESULTS: A drain opening was made under the superficial
      scleral flap in the site of pars plana projection and was further used for local
      vitrectomy in the form of a wide well directed to the posterior pole of the eye.
      In 51.5% of cases normal ocular pressure was achieved without antihypertensive
      drops. In the rest of cases there was a tendency for ocular hypertension and
      therapeutic regimen was required. Pain relief after the surgery was achieved in
      all eyes. CONCLUSION: Vitreous drainage is an effective technique for pain
      elimination in terminal-stage refractory glaucoma. The presumable mechanism of
      action involves creating an opportunity for easy evacuation of osmotically active
      substances (urea in the first place) along with the humour from the vitreous
      cavity. The operation enables direct draining of the vitreous cavity regardless
      of organic changes in the anterior chamber that impede the outflow.

PMID- 24684063
TI  - [The effect of fibrinolytic therapy for proliferative diabetic retinopathy
      complications on the angiogenic potential of the eye].
AB  - OBJECTIVE: To investigate dynamic changes of pathogenically significant factors
      of tear fluid in type 2 diabetes patients with hemorrhagic proliferative diabetic
      retinopathy. MATERIAL AND METHODS: A total of 30 patients (30 eyes) with type 2
      diabetes mellitus and proliferative diabetic retinopathy complicated by
      preretinal and vitreous hemorrhages were assessed and treated with recombinant
      prourokinase (Gemaza). Levels of VEGF A, MCP-1, MMP-2, and MMP-9 in tear fluid
      were also measured. RESULTS: Intravitreal injections of recombinant prourokinase
      led to more considerable gain of visual acuity and decrease of vitreous
      hemorrhage index in the first 24 hours in comparison with other treatment
      schemes. Changes of VEGF A and MCP-1 tear levels were insignificant. Increase of
      matrix proteinases activity was mainly due to MMP-9. CONCLUSION: The use of
      recombinant prourokinase is associated with clinical improvement in patients with
      hemorrhagic diabetic retinopathy causing no notable changes in tear levels of
      proangiogenic cytokines and matrix proteinases.

PMID- 24684064
TI  - [Morphometric assessment of the macula in spongiform macular edema treated with
      antivasoproliferative therapy].
AB  - Antivasoproliferative therapy is a pathogenetic treatment for diabetic macular
      edema. The objective of the study was to investigate the effect of ranibizumab on
      foveolar parameters in spongiform macular edema. A total of 37 patients (38 eyes)
      with spongiform macular edema were assessed and given antivasoproliferative
      therapy with ranibizumab. Optical coherence tomography showed a reduction of the
      total retinal thickness by 44 microm (from 306 +/- 77 microm to 262 +/- 30
      microm, p < 0.05). The pigment epithelium thickness within the central area
      changed from 21 +/- 4 microm to 40 +/- 9 microm. The maximum decrease of the
      outer nuclear layer thickness was noted in 400 +/- 100 microm from foveola and
      averaged from 72 +/- 19 microm to 29 +/- 6 microm with its gradual increase to
      the periphery to 100 +/- 8 microm.

PMID- 24684065
TI  - [Clinical and immunological features of stress reactivity in the dynamics of
      ocular burn].
AB  - A series of clinical and immunological studies revealed peculiarities of stress
      reactivity in the course of ocular burn. According to adrenergic receptor
      expression level in active T-lymphocytes and its trend in the dynamics of ocular
      burn 2 types and 7 variants of individual adrenergic immune reactivity were
      identified and a physiologically adequate variant of stress reactivity was
      determined.

PMID- 24684066
TI  - [Ultrasonography in normal eyelids assessment].
AB  - The article presents the results of a complex study on ultrasonography which
      included high-resolution grey scale B-scan, color Doppler imaging, and ultrasonic
      density measurement of eyelids and periorbital tissues. A total of 48 patients
      were enrolled. Echographic anatomy of eyelid layers, i.e. skin, orbicularis oculi
      muscle, tarsus, and orbital fat, is described in detail. Depth and ultrasonic
      density values for all layers are provided. The authors suggest performing an
      ultrasound examination of eyelids prior to reconstructive and plastic surgery in
      order to facilitate the choice of surgical tactics.

PMID- 24684067
TI  - [Pathogenetic relationship between pterygium and dry eye syndrome (clinical and
      cytological study)].
AB  - OBJECTIVE: To study the prevalence of dry eye syndrome in patients with initial
      primary pterygium for determination of a possible pathogenetic role of dry eye
      syndrome in the development of pterygium. MATERIAL AND METHODS: 30 patients with
      initial primary pterygium; besides conventional ophthalmic assessment,
      cytological examination of bulbar conjunctiva was performed in all cases.
      RESULTS: Signs of dry eye syndrome, of similar severity in both eyes, were found
      in 100% of patients. CONCLUSION: Dry eye can be one of the precipitating factors
      of primary pterygium.

PMID- 24684068
TI  - [Color visual field to red and blue stimuli].
AB  - The boundaries of color visual field (CVF) in individuals with normal vision were
      studied under various signal detection criteria: natural (standard instructions),
      conservative (strict), and liberal (easy). The study enrolled 112 volunteers
      (20.40 +/- 1.45 years, M +/- SD) and was performed on an automated perimeter HFA
      II-750i ("Carl Zeiss Meditec, Inc."; USA) using red and blue stimuli of four
      discrete intensities with 10 log units increments. It was shown that blue color
      sensitivity reduces from the center of visual field to its periphery faster than
      red one. The use of the conservative criterion resulted in narrowing of CVF to
      both red and blue targets. With the liberal criterion applied CVF to red expands,
      while CVF to blue remains of the same size. Size changes of CVF are more
      significant when switching from the natural criterion to the conservative rather
      than to the liberal one.

PMID- 24684069
TI  - [Tanning lamp radiation-induced photochemical retinal damage].
AB  - On the basis of original clinical research a rare case of bilateral retinal
      damage due to tanning lamp radiation exposure is presented. Along with
      significant decrease of visual acuity and light sensitivity of central visual
      field as well as color vision impairment, bilateral macular dystrophy was found
      during an ophthalmoscopy and confirmed by optical coherent tomography and
      fluorescent angiography. Intensive retinoprotective, vascular, and antioxidant
      therapy was effective and led to functional improvement and stabilization of the
      pathologic process associated with photochemical retinal damage. A brief review
      of literature compares mechanisms of retinal damage by either short or long-wave
      near visible radiation.

PMID- 24684070
TI  - [New method for treatment of chronic blepharitis associated with dry eye
      syndrome].
AB  - A new combined method for treatment of chronic blepharitis associated with dry
      eye syndrome is developed. A total of 25 patients were enrolled. The treatment
      implied the use of artificial tears, Restasis, and Blephasteam spectacle frame.
      The course included 20 procedures on daily basis. The monitoring period was 1
      year. A pronounced anti-inflammatory, reparative, and moistening effect as well
      as stabilization of the precorneal film was achieved in short time. Owing to the
      combined approach, negative side effects (such as burning, conjunctival
      irritation, and fluctuating vision) were minimized. Repeated treatment courses
      maintained the positive therapeutic effect and prolongated the remission.

PMID- 24684071
TI  - [Clinical presentation, diagnosis, and treatment of ocular manifestations of
      generalized and secondary focal yersiniosis].
AB  - The article describes possible clinical presentation, diagnosis, and treatment of
      ocular manifestations of generalized and secondary focal yersiniosis. Treatment
      experience of 32 patients (60 eyes) with episcleritis, scleritis,
      chorioretinitis, and anterior and posterior uveitis associated with generalized
      and secondary focal yersiniosis is reviewed. In order to clarify disease
      etiopathogenisis conventional ophthalmic assessment as well as clinical and
      immunological laboratory tests, including HLA typing, were performed. All
      patients also consulted an infectiologist, rheumatologist, urologist,
      gynecologist, etc. Treatment strategy implied the use of anti-infectious and anti
      inflammatory agents, antisensitizers, and drugs capable of improving
      intracellular immunity, therapy staging, and providing a comprehensive effect on
      different components of the pathologic process. Due to polymorphism of
      yersiniosis, all patients with autoimmune eye diseases are to be tested for
      specific antibodies to Yersiniae.

PMID- 24684072
TI  - [Combined transscleral and transpupillary thermotherapy in large
      vasoproliferative retinal tumors].
AB  - Three cases (two patients) of large vasoproliferative retinal tumor treatment by
      an original method, which includes intraoperative non-contact transscleral
      thermotherapy and subsequent transpupillary thermotherapy, are described.
      Positive anatomical results were achieved in all three cases.

PMID- 24684073
TI  - [Modern methods of astigmatism correction in cataract surgery].
AB  - Modern methods of astigmatism correction in lens surgery are reviewed in the
      article. Keratorefractive, including laser-assisted, and intraocular techniques
      employing different models of toric intraocular lenses (IOL) are described.
      Current state of the problem is analyzed. Implantation of toric IOLs enables
      precise correction of corneal astigmatism simultaneously with cataract
      phacoemulsification.

PMID- 24684074
TI  - [Photorefractive surgery in non-standard clinical situations].
AB  - The article discusses options for correction of residual ametropia after previous
      refractive surgeries (radial keratotomy, corneal transplantation) and treatment
      of corneal opacification resulting from excimer laser surgeries.

PMID- 24684075
TI  - Clarifying the links between grandiose narcissism and parenting.
AB  - This study investigated the links between parenting and grandiose narcissism in
      hopes of clarifying recent empirical discrepancies. One-hundred forty-five
      participants completed the Narcissistic Personality Inventory and reported about
      their parents' support, coldness, monitoring, psychological control, and
      overvaluation. Psychological control was associated positively with narcissism,
      whereas monitoring and coldness were associated negatively. Overvaluation and
      parental support showed no reliable associations with narcissism. Analysis of the
      components of narcissism further elucidated these links. The results are
      interpreted in light of previous findings and as consistent with social learning
      and psychodynamic theories regarding the origins of narcissism.

PMID- 24684076
TI  - Independent and joint effects of personality on intentions to become an active
      participant in local union activities in Canada.
AB  - Drawing on the theory of planned behavior (TPB), this field study (N = 282)
      investigates the impact of two focal personality traits, extraversion and
      conscientiousness, on employees' attitudes and intentions to actively participate
      in their local union. Consistent with the TPB, subjective norms, perceived
      behavioral control, and attitudes toward participation each explained unique
      variance in union participation intentions. Furthermore, results revealed that
      extraversion was positively related, and conscientiousness was negatively related
      to participation intentions, with attitudes toward participation mediating these
      effects. A significant interaction between extraversion and conscientiousness was
      also observed, such that introverted workers higher in conscientiousness were
      less inclined to express positive attitudes toward union participation. Overall,
      these results provide support for the utility of the TPB in predicting union
      participation intentions and highlight the vital role that personality traits may
      play in determining union participation attitudes and intentions.

PMID- 24684077
TI  - Verbal redundancy aids memory for filmed entertainment dialogue.
AB  - Three studies investigated the effects of presentation modality and redundancy of
      verbal content on recognition memory for entertainment film dialogue. U.S.
      participants watched two brief movie clips and afterward answered multiple-choice
      questions about information from the dialogue. Experiment 1 compared recognition
      memory for spoken dialogue in the native language (English) with subtitles in
      English, French, or no subtitles. Experiment 2 compared memory for material in
      English subtitles with spoken dialogue in English, French, or no sound.
      Experiment 3 examined three control conditions with no spoken or captioned
      material in the native language. All participants watched the same video clips
      and answered the same questions. Performance was consistently good whenever
      English dialogue appeared in either the subtitles or sound, and best of all when
      it appeared in both, supporting the facilitation of verbal redundancy.
      Performance was also better when English was only in the subtitles than when it
      was only spoken. Unexpectedly, sound or subtitles in an unfamiliar language
      (French) modestly improved performance, as long as there was also a familiar
      channel. Results extend multimedia research on verbal redundancy for expository
      material to verbal information in entertainment media.

PMID- 24684078
TI  - Compulsory citizenship behavior and organizational citizenship behavior: the role
      of organizational identification and perceived interactional justice.
AB  - This article examines the psychological mechanism underlying the relationship
      between compulsory citizenship behavior (CCB) and organizational citizenship
      behavior (OCB) by developing a moderated mediation model. The model focuses on
      the mediating role of organizational identification and the moderating role of
      interactional justice in influencing the mediation. Using a time-lagged research
      design, the authors collected two waves of data from 388 supervisor-subordinate
      dyads in 67 teams to test the moderated mediation model. Results revealed that
      CCB negatively influenced OCB via impairing organizational identification.
      Moreover, interactional justice moderated the strength of the indirect effect of
      CCB on OCB (through organizational identification), such that the mediated
      relationship was stronger under low interactional justice than under high
      interactional justice.

PMID- 24684079
TI  - Parenting influences on bicycle helmet rules and estimations of children's helmet
      use.
AB  - The present study examined the potential relationship between parenting variables
      and estimations of children's bicycle helmet use. Parents (N = 121) completed
      surveys asking about parental monitoring and questions about their bicycle habits
      and attitudes, as well as their expectations for their children to wear a helmet
      and their estimation of how often their children wear a helmet. Parents reported
      stronger helmet rules for their children who are beginning cyclists rather than
      experienced cyclists, and rules for experienced cyclists were more strongly
      endorsed among parents who reported more parental monitoring as well. Parents who
      wear helmets themselves endorsed stronger helmet rules for their experienced
      riders, compared to parents who do not wear helmets. Parents without helmet rules
      reported more peer pressure in that they were more likely to agree that their
      friends do not make their kids wear helmets and that their child's friends do not
      wear helmets. In addition, believing other parents do not wear helmets and
      believing one's child's friends do not wear helmets were both associated with a
      lower likelihood that their children wear a helmet. This appears to be the first
      study linking perceptions of parental peer pressure with helmet rules and use.
      For public health reasons, it is imperative to examine parental factors that may
      establish children's helmet wearing.

PMID- 24684080
TI  - When supervisors perceive non-work support: test of a trickle-down model.
AB  - Using the trickle-down model as the theoretical foundation, we explored whether
      subordinates' perceived supervisory non-work support (subordinates' PSNS)
      mediates the relationship between supervisors' perception of higher-level
      managers' non-work support (supervisors' PSNS) and subordinates' organizational
      citizenship behaviors. Using dyadic data collected from 132 employees and their
      immediate supervisors, we found support for the aforementioned mediation process.
      Furthermore, supervisors' perceived in-group/out-group membership of subordinates
      moderated the aforementioned supervisors' PSNS-subordinates' PSNS relationship,
      such that this relationship is stronger for out-group subordinates. Theoretical
      and practical implications and future research directions are discussed.

PMID- 24684081
TI  - Capital-labor struggle: the unspoken causes of the crises.
AB  - The literature on the causes of the current financial and economic crises often
      fails to consider both the causal role of the conflict between capital and labor,
      and this conflict's continued effect. This article analyzes the evolution of the
      conflict and its implications for the distribution of income during the post
      World War II period. Especially emphasizing the relationship between the U.S. and
      European economies, it examines the genesis and development of the governing
      structures of the Eurozone as determining factors in the increasing gap between
      capital and labor. The history of the European economic trajectory and the
      current German financial leadership provide important context for the analysis.
      Evidence is provided that this conflict between capital and labor is at the roots
      of the current financial and economic crisis, a thesis has been dramatically
      underexposed in the current scientific literature.

PMID- 24684082
TI  - Health issues and health care expenses in Canadian bankruptcies and insolvencies.
AB  - Illness can contribute to financial problems directly, through high medical
      bills, and indirectly, through lost income. No previous in-depth studies have
      documented the role of medical problems among Canadian bankruptcy filers. We
      obtained the bankruptcy filings from a random sample of 5,000 debtors across
      Canada and mailed surveys to them seeking information about the medical
      antecedents of their bankruptcy. A total of 521 debtors responded (response rate
      of 10.4%), of whom 40.1 percent reported losing at least two weeks of work
      related income because of illness or injury in the two years before their filing;
      8.3 percent reported a similar income loss because of caregiving responsibilities
      for someone else who was ill. Although 60.1 percent of respondents reported being
      responsible for a medical bill within the previous two years, only 6.9 percent
      had bills over $5,000 (all amounts in Canadian Dollars). Prescription drugs were
      cited as the costliest medical expense by two-thirds of debtors reporting bills >
      $5,000, with dental bills cited by 22.2 percent. Universal health insurance
      affords Canadians protection against ruinous doctor and hospital bills.
      Inadequate coverage for prescription drugs and dental care, however, leaves some
      with unaffordable out-of-pocket costs. In addition, illness is a frequent
      indirect cause of bankruptcy through loss of work-related income.

PMID- 24684083
TI  - The painful effects of the financial crisis on Spanish health care.
AB  - Spain has an advanced, integrated health care system that has achieved remarkable
      results, including substantially improved health outcomes, over a relatively
      short time. Measures introduced by central and regional governments to combat the
      financial crisis may be severely affecting the health sector, with proposed
      changes potentially threatening the principles of equity and social cohesion
      underlying the welfare state. This article examines recent developments in
      Spanish health care, focusing on the austerity measures introduced since 2010. In
      Spain, as in other countries, evaluation of health care changes is difficult due
      to the paucity of data and because the effects of measures often lag well behind
      their introduction, meaning the full effects of changes on access to care or
      health outcomes only become apparent years later. However, some effects are
      already clear. With exceptions, Spain has not used the crisis as an opportunity
      to increase efficiency and quality, rationalize and reorganize health services,
      increase productivity, and regain public trust. We argue that immediate health
      care cuts may not be the best long-term answer and suggest evidence-driven
      interventions that involve the portfolio of free services and the private sector,
      while ensuring that the most vulnerable are protected.

PMID- 24684084
TI  - The impact of Thatcherism on health and well-being in Britain.
AB  - Margaret Thatcher (1925-2013) was the United Kingdom's prime minister from 1979
      to 1990. Her informal transatlantic alliance with U.S. President Ronald Reagan
      from 1981 to 1989 played an important role in the promotion of an international
      neoliberal policy agenda that remains influential today. Her critique of UK
      social democracy during the 1970s and her adoption of key neoliberal strategies,
      such as financial deregulation, trade liberalization, and the privatization of
      public goods and services, were popularly labeled Thatcherism. In this article,
      we consider the nature of Thatcherism and its impact on health and well-being
      during her period as prime minister and, to a lesser extent, in the years that
      follow; we focus mainly on Great Britain (England, Scotland, and Wales).
      Thatcher's policies were associated with substantial increases in socioeconomic
      and health inequalities: these issues were actively marginalized and ignored by
      her governments. In addition, her public-sector reforms applied business
      principles to the welfare state and prepared the National Health Service for
      subsequent privatization.

PMID- 24684085
TI  - Does autonomization of public hospitals and exposure to market pressure
      complement or debilitate social health insurance systems? Evidence from a low
      income country.
AB  - Granting public hospitals greater autonomy and creating organizational
      arrangements that mimic the private sector and encourage competition is often
      promoted as a way to increase efficiency and public accountability and to improve
      quality of care at these facilities. The existence of good-quality health
      infrastructure, in turn, encourages the population to join and support the social
      health insurance system and achieve universal coverage. This article provides a
      critical review of hospital autonomization, using Vietnam's experience to assess
      the influence of hospital autonomy on the sustainability of Vietnam's social
      health insurance. The evidence suggests that a reform process based on greater
      autonomy of resource mobilization and on the retention and use of own-source
      revenues can create perverse incentives among managers and health care providers,
      leading to the development of a two-tiered provision of clinical care, provider
      induced supply of an inefficient service mix, a high degree of duplication,
      wasteful investment, and cost escalation. Rather than complementing social health
      insurance and helping the country to achieve universal coverage, granting public
      hospitals greater autonomy that mimics the private sector may indeed undermine
      the legitimacy and sustainability of social health insurance as health care costs
      escalate and higher quality of care remains elusive.

PMID- 24684086
TI  - "Trade creep" and implications of the Transatlantic Trade and Investment
      Partnership Agreement for the United Kingdom National Health Service.
AB  - The ambitious and comprehensive Transatlantic Trade and Investment Partnership
      Agreement (TTIP/TAFTA) agreement between the European Union and United States is
      now being negotiated and may have far-reaching consequences for health services.
      The agreement extends to government procurement, investment, and further
      regulatory cooperation. In this article, we focus on the United Kingdom National
      Health Service and how these negotiations can limit policy space to change
      policies and to regulate in relation to health services, pharmaceuticals, medical
      devices, and health industries. The negotiation of TTIP/TAFTA has the potential
      to "harmonize" more corporate-friendly regulation, resulting in higher costs and
      loss of policy space, an example of "trade creep" that potentially compromises
      health equity, public health, and safety concerns across the Atlantic.

PMID- 24684087
TI  - Work, health, and welfare: the association between working conditions, welfare
      states, and self-reported general health in Europe.
AB  - This article is the first to examine the association between self-reported
      general health and a wide range of working conditions at the European level and
      by type of welfare state regime. Data for 21,705 men and women ages 16 to 60 from
      27 European countries were obtained from the 2010 European Working Conditions
      Survey. The influence of individual-level sociodemographic, physical, and
      psychosocial working conditions and of the organization of work were assessed in
      multilevel logistic regression analyses, with additional stratification by
      welfare state regime type (Anglo-Saxon, Bismarckian, Eastern European,
      Scandinavian, and Southern). At the European level, we found that "not good"
      general health was more likely to be reported by workers more exposed to
      hazardous working conditions. Most notably, tiring working positions, job strain,
      and temporary job contracts were strongly associated with a higher likelihood of
      reporting "not good" health. Analysis by welfare state regime found that only
      tiring or painful working conditions were consistently associated with worse self
      reported health in all regimes. There was no evidence that the Scandinavian
      welfare regime protected against the adverse health effects of poor working
      conditions. The article concludes by examining the implications for comparative
      occupational health research.

PMID- 24684088
TI  - Limits to neoliberal reforms in the health sector: the case of pharmaceutical
      management in New Zealand.
AB  - In New Zealand in 1993, a pharmaceutical management agency (PHARMAC) was
      established during the height of neoliberal reforms in the health sector. The
      agency's relationship with pharmaceutical companies, patient lobby groups, and
      health professionals has been hostile at times, but despite this hostility,
      PHARMAC has remained substantially independent from political interference. This
      article draws on critical theory and Durkheimian perspectives to explain how such
      a strong regulatory organization was established during a time when attempts were
      made to reshape the health sector to conform to a neoliberal agenda. An analysis
      of historical and contemporary issues demonstrates the contradictory position of
      the state in relation to the regulation and subsidization of pharmaceuticals,
      with conflicting demands to retain popular support, restrain state expenditure,
      and respond to expectations to provide pharmaceuticals to its citizens. This
      article demonstrates how the establishment of PHARMAC reconciles these
      contradictory demands, arguing that it removes decision making from political
      control and has been able to sustain its place by appealing to objective
      assessment criteria. This case signals limits of the neoliberal agenda.

PMID- 24684089
TI  - Social differentials in non-employment following hospital admission for
      musculoskeletal disorders in Sweden, 2001-2006.
AB  - The article studies social differentials in non-employment among individuals who
      had been employed in 2001 following hospital admission for musculoskeletal
      disorders, by gender, educational level, and country of birth, in Stockholm
      County during 2001-2006. Individually linked population registers on health
      service use and sociodemographic characteristics were used. Individuals ages 25
      to 59, living in Stockholm County and having employment in 2001, were followed
      until 2006. Annual age-standardized employment rates were calculated for people
      admitted to the hospital and diagnosed with a musculoskeletal disorder (n =
      1,888) and compared to a reference group of others in employment. Multivariate
      Cox regression analysis was used to calculate the hazard risks of non-employment
      in 2006. Both women and men admitted to the hospital had lower age-standardized
      employment rates compared to the reference group and were at higher risk of non
      employment. The hazard risk of non-employment was significantly higher among
      women and men with short education and among foreign-born individuals. Employment
      consequences of musculoskeletal disorders seem to be unequally distributed
      between different social groups, with women, people with short education, and
      people born outside Sweden more likely to be non-employed.

PMID- 24684090
TI  - Horizontal inequality in rationing by waiting lists.
AB  - The objective of this article was to investigate the existence of horizontal
      inequality in access to care for six categories of elective surgery in a publicly
      funded system, when care is rationed through waiting lists. Administrative
      waiting time data on all elective surgeries (n = 4,634) performed in
      Ostergotland, Sweden, in 2007 were linked to national registers containing
      variables on socioeconomic indicators. Using multiple regression, we tested five
      hypotheses reflecting that more resourceful groups receive priority when
      rationing by waiting lists. Low disposable household income predicted longer
      waiting times for orthopedic surgery (27%, p < 0.01) and general surgery (34%, p
      < 0.05). However, no significant differences on the basis of ethnicity and gender
      were detected. A particularly noteworthy finding was that disposable household
      income appeared to be an increasingly influential factor when the waiting times
      were longer. Our findings reveal horizontal inequalities in access to elective
      surgeries, but only to a limited extent. Whether this is good or bad depends on
      one's moral inclination. From a policymaker's perspective, it is nevertheless
      important to recognize that horizontal inequalities arise even though care is not
      rationed through ability to pay.

PMID- 24684091
TI  - Making the most of open windows: establishing health in all policies in South
      Australia.
AB  - Significant improvements in population health are likely to arise when the social
      determinants ofhealth are addressed. This creates a challenge for health systems,
      as the policy levers to influence the determinants largely lie outside of their
      direct control. Health agencies have been attempting to develop responses that
      affect these policy levers with mixed success. Success often requires particular
      conditions or "windows of opportunity" to be present before even small systemic
      change can be made. The government of South Australia has developed a practical,
      policy-oriented response to address the determinants of health--Health in All
      Policies--and has been successfully working across government for the past five
      years, using a policy learning process to implement this approach. This article
      will focus on how the South Australian Health in All Policies initiative started
      and the conditions that enabled South Australia to establish a centralized
      governance structure, harness a group of cross-sector policy entrepreneurs, and
      conduct health lens projects across a range of policy issues. The authors will
      comment on the nature of these conditions and their relevance for other
      governments struggling to reduce the burden of chronic disease and growing health
      budgets by addressing the social determinants of health.

PMID- 24684092
TI  - The diverse and rapidly growing HIV epidemic in the WHO Eastern Mediterranean
      region: will countries succeed in their control?

PMID- 24684093
TI  - Prevalence and determinants of condom utilization among people living with
      HIV/AIDS in Egypt.
AB  - Condoms are an integral part of HIV/AIDS prevention, yet their use is affected by
      several factors. The purpose of this study was to determine the prevalence of
      condom use and the psychological and behavioural determinants among people living
      with HIV/AIDS in Egypt. Focus group discussions were used to develop the study
      tool (questionnaire interview) geared towards eliciting knowledge, attitudes and
      beliefs about condoms among 338 confirmed HIV-positive persons attending fixed
      voluntary counselling and testing centres in 8 governorates in Egypt. The
      prevalence of condom use was 45.0% in regular sexual relations and only 18.1% in
      casual relations. The determinants of condom use were: type of partner,
      serostatus of partner, antiretroviral intake, beliefs and attitudes towards
      condom use and to HIV infection. The study shows that special efforts need to be
      made to change the attitudes of people living with HIV/AIDS towards condom use.

PMID- 24684094
TI  - High prevalence of HCV coinfection in HIV-infected individuals in Shiraz, Islamic
      Republic of Iran.
AB  - We carried out a cross-sectional survey in Shiraz to determine the prevalence of
      hepatitis C virus (HCV) in 1 444 individuals infected with human immunodeficiency
      virus (HIV). We also determined the risk factors for this coinfection.
      Demographic and behavioural data were obtained using a standard questionnaire.
      The prevalence of HIV-HCV coinfection was 78.4% (95% CI: 76.3-80.5). Intravenous
      drug use (OR = 7.2; 95% CI: 4.9-10.6), imprisonment (OR = 6.9; 95% CI: 4.6-10.4),
      tattooing in prison (OR = 2.61; 95% CI: 1.4-4.8), tattooing out of prison (OR =
      2.0; 95% CI: 1.3-3.1) and age (OR = 1.02 with increasing each year of life; 95%
      CI: 1.0-1.04) were significantly associated with HCV-HIV coinfection. Prevalence
      of HCV-HIV coinfection is high in Shiraz. Intravenous drug use and imprisonment
      are the main risk factors for this coinfection. Therefore, serious implementation
      of HIV and HCV testing, education, prevention, care and treatment programmes and
      evaluation of harm reduction programmes in prisons are very important.

PMID- 24684095
TI  - Knowledge of and attitudes towards sexual and reproductive health in adults in
      Shiraz: a need for further education.
AB  - Sexual health influences general well-being and the overall quality of life of
      all men and women. This study in Shiraz, Islamic Republic of Iran, aimed to
      assess the level of knowledge of and attitudes towards sexual and reproductive
      health among adults. In a cross-sectional study in 2010, 276 men and 281 women
      were recruited at pre-marital counselling courses and completed a 33-item
      anonymous questionnaire in private. The overall level of knowledge of men and
      women was low. Both men and women had low scores on knowledge of genital anatomy,
      sexually transmitted infections and contraceptive use. The majority of
      participants had positive attitudes towards implementing educational programmes
      on sexual and reproductive health issues for young adults and prior to marriage.
      Efficient educational programmes providing up-to-date information about sexual
      and reproductive health are needed in the Islamic Republic of Iran.

PMID- 24684096
TI  - First evaluation of the serum level of anti-hepatitis B surface antigen after
      vaccination in Libya.
AB  - The hepatitis B virus (HBV) vaccination schedule in Libya follows international
      recommendations (1st dose at birth, 2nd after 1 month and 3rd after 6 months).
      This research aimed to evaluate the long-term protection of the HBV immunization
      programme in Tripoli and to determine the best age to administer booster doses.
      Serum levels of hepatitis B surface antigen were determined in 277 randomly
      selected children aged 1-12 years. The response to HBV vaccine in 1-3-year-olds
      was 93.2%, but this declined with age and at 7-9 years after initial vaccination
      only 53.1% of children had protective titres (> or = 10 mIU/mL). No significant
      differences between males and females in antibody persistence or response to
      vaccine were observed. We recommend continuing the HBV vaccination programme and
      that a booster dose be given to 6-year-old children to ensure maximum protection
      during the period of school entry and beyond.

PMID- 24684097
TI  - Effect of chronic diseases of lifestyle knowledge on readiness for change among
      long-distance microbus drivers in Giza, Egypt.
AB  - Commercial drivers suffer from sedentary lifestyles, poor nutrition and numerous
      stressors that can impact their health. This study aimed to assess the health
      lifestyle risk level of microbus drivers in Giza, Egypt, and to compare their
      level of readiness for change with their knowledge about chronic diseases of
      lifestyle, before and after an educational intervention. Data were collected from
      235 long-distance microbus drivers via a health lifestyle assessment
      questionnaire, pre-post-tests of a health education module, and the readiness for
      change questionnaire. The majority of drivers had high risk scores in the eating
      habits, exercises/fitness and safety sections. A highly significant difference
      was found in chronic diseases of lifestyle knowledge scores and in readiness for
      change scores before and after the intervention. A positive correlation was found
      between readiness for change and knowledge pre- and post-intervention. Further
      studies are needed of barriers for drivers to change their health lifestyles.

PMID- 24684098
TI  - Lifetime and current waterpipe use among adolescents in Tehran, Islamic Republic
      of Iran.
AB  - Waterpipe use among Iranian adolescents has become a matter for concern. A
      descriptive, cross-sectional community-based survey was performed in 2010 to
      determine the prevalence of waterpipe use and associated factors among Iranian
      adolescents in Tehran, Islamic Republic of Iran. After multi-stage, random
      cluster sampling 1201 adolescents aged 15-18 years old responded to a
      questionnaire based on the Youth Risk Behavior Surveillance. The prevalence of
      current waterpipe smoking (at least once in the previous 30 days) was 28.0%,
      significantly higher among males (34.8%) than females (21.4%). A total of 45.1%
      of adolescents reported lifetime use (ever use) of waterpipes and 34.2% had ever
      shared a waterpipe. In multivariate logistic regression analysis the significant
      correlates of current waterpipe use for both males and females were having
      smokers among friends and family members, while for males, older age and
      educational failure were also risk factors.

PMID- 24684099
TI  - Overweight and obesity among Jordanian women and their social determinants.
AB  - This study aimed to explore the social determinants associated with obesity among
      Jordanian women using the national data from the Jordan Population and Family
      Health Survey 2009. We found the overall prevalence of overweight was 30% and
      obesity was 38.8% among Jordanian women aged 15-49 years. Results of multivariate
      analysis showed that age; residing in the south region of Jordan, marriage at an
      early age, parity, wealth status and smoking were statistically significant
      predictors of overweight and obesity among women in Jordan. Our results show that
      there is an urgent need to implement health programmes to prevent and control
      overweight and obesity at the national level. Social determinants should be
      taking into consideration in designing. and implementing these programmes.

PMID- 24684100
TI  - Overview of medical schools in the Eastern Mediterranean Region of the World
      Health Organization.
AB  - The 22 countries of the Eastern Mediterranean Region (EMR) exhibit considerable
      diversity, both culturally and economically. This paper collated published data
      on the status of medical schools in the Region to provide information to assist
      in future planning. Information about medical schools was obtained from the
      International Medical Education Directory, the Avicenna Directory, the WHO/EMR
      Health Professions Education Directory and the Institute for International
      Medical Education's Database of Medical Schools. The registered number of medical
      schools in the Region varied according to the different directories. There were
      variations in the language used for instruction (some used more than one
      language) and the density of medical schools per million population. The density
      and number of medical schools in the country were not related to the number of
      working physicians which ranged from 2.1 per 10 000 population in Afghanistan to
      28.3 in Egypt. An updated directory of medical schools in the Region is much
      needed.

PMID- 24684101
TI  - Living arrangements of older adults in Lebanon: correlates of living with married
      children.
AB  - Rapid increases in the proportion of older adults in the population present major
      challenges to policy-makers worldwide. Using a nationally representative sample
      from the PAPFAM survey in Lebanon, this study examined the living arrangements of
      older adults (aged > or = 65 years), and their correlates, with a focus on co
      residence with married children. Of 1774 older adults 17.1% co-resided with their
      married children: 28.1% of the 559 unmarried (widowed/divorced/single) and 11.3%
      of the 1071 married older adults. Among both the married and unmarried, the
      likelihood of co-residence was significantly lower in regions outside the capital
      and decreased with increasing socioeconomic status. Among the unmarried elderly,
      co-residence with a married child was also significantly associated with
      increasing age and availability of sons, as well as presence of a vascular
      disorder and speech problems. While solitary living has traditionally been the
      focus for policy-makers, older people living with a married child may also be a
      vulnerable group.

PMID- 24684102
TI  - Ascaris lumbricoides causing acute abdomen: a case report.

PMID- 24684103
TI  - [Electroacupuncture intervention combined with general anesthesia for 80 cases of
      heart valve replacement surgery under cardiopulmonary bypass].
AB  - OBJECTIVE: To determine whether electroacupuncture (EA) intervention combined
      with general anesthesia (GA) strategy can reduce early post-operative morbidity
      and medical costs in patients undergoing heart valve replacement operation under
      cardiopulmonary bypass. METHODS: A total of 160 heart valve replacement surgery
      patients undergoing cardiopulmonary bypass were randomly divided into GA and EA +
      GA groups (n = 80 in each group). Patients of the GA group were given with
      intravenous injection of Fentanyl, Midazolam, Vecuronium Bromide, etc. and
      routine tracheal intubation. EA (3-4 Hz, 2.0-2.2 mA) was applied to bilateral
      Zhongfu (LU 1), Chize (LU 5) and Ximen (PC 4) beginning about 20 mm before the
      surgery in the EA + GA group. Endotracheal intubation was not employed but only
      prepared as a standby for patients of the EA + GA group. The dosage of narcotic
      drugs, duration of surgery, duration of aertic blockage, rate of cardiac re
      beating, volumes of post-operative blood transfusion, discharge volume, cases of
      post-operative pulmonary infection, vocal cord injury, and the time of first bed
      off, first eating and duration in intensive care unit (IOU) residence. etc. were
      recorded. RESULTS: The successful rates of heart valve replacement surgery were
      similar in both GA and EA + GA groups. Compared with the GA group, the dosages of
      Fentanyl, Midazolam and Vecuronium of the EA + GA group were significantly lower
      (P < 0.05, P < 0.01), the numbers of patients needing blood-transfusion,
      antibiotics treatment, and suffering from pulmonary infection were fewer, the
      time of first bed-off and duration of hospitalizetion and IOU residence were
      considerably shorter (P < 0.05, P < 0.01) and the total medical cost was
      obviously lower (P < 0.05) in the EA + GA group. CONCLUSION: EA combined with
      general anesthesia strategy for heart valve replacement surgery without
      endotracheal intubation is safe and can reduce post-operative morbidity and
      medical costs in patients undergoing heart valve replacement surgery under
      cardiopulmonary bypass.

PMID- 24684104
TI  - [Effects of transcutaneous electrical acupoint stimulation combined with general
      anesthesia on cerebral oxygen metabolism in elderly hip replacement patients
      during controlled hypotension].
AB  - OBJECTIVE: To observe the protective effect of transcutaneous electrical acupoint
      stimulation (TEAS) on cerebral tissue in elderly hip replacement operation
      patients during general anesthesia under controlled hypotension. METHODS: Forty
      hip replacement operation patients were randomly divided into general anesthesia
      (GA) control group and TEAS + GA group (n = 20 in each group). Patients of the
      two groups during operation were treated with controlled hypotension for reducing
      blood loss. TEAS (2 Hz/100 Hz, 8-12 mA) was applied to bilateral Yuyao (EX-HN 4)
      and Fengchi (GB 20) and began 30 min before GA. General anesthesia was performed
      by intravenous injection of Midazolam, Diprivan, Fentanyl and Cis-atracurium,
      sevoflurane-inhaling, Remifentanil, etc., and the patient's mean arterial
      pressure was maintained to be about 70% of the normal level (controlled
      hypotension) by using venous administration of Remifentanil about 10 min after
      the operation. GEM Premier 3000 blood gas analyzer was used to analyze levels of
      the arterial oxygen (CaO2), internal jugular venous oxygen (CjvO2), arterio
      venous oxygen content difference (Da-jvO2) and cerebral oxygen (CERO2) uptake
      rates of blood samples before controlled hypotension (T0), 20 min after
      controlled hypotension (T ). 40 min after controlled hypotension (T2) and 20 min
      after the end of controlled hypotension (T3). RESULTS: Self-comparison of each
      group showed that in comparison with pre-controlled hypotension, CjvO2 levels at
      the time-points of T, T2 and T3 were significantly increased in both GA control
      and TEAS+GA groups (P < 0.05), while Da-jvO2 and CERO2 uptake rate levels at the
      time-points of T,. T2 and T3 in these two groups were significantly decreased (P
      < 0.05). Comparison between two groups showed that CivO2 levels at the time
      points of T2 and T3 were significantly higher in the TEAS + GA group than in the
      GA control group (P<0. 05). while Da-jvO2 and CERO2 uptake rate levels at the
      time-point of T2 were obviously lower in the TEAS + GA group than in the GA
      control group(P<0. 05), suggesting a reduction of cerebral oxygen consumption
      after TEAS. No significant differences were found between these two groups in
      blood CjvO2, Da-jvO2 and CERO2 uptake rate levels at the time-points of T0 and T1
      (P > 0.05). CONCLUSION: TEAS can reduce cerebral oxygen uptake rate in elderly
      patients undergoing hip replacement during controlled hypotension, suggesting a
      protective effect of TEAS on patient's cerebral tissue.

PMID- 24684105
TI  - [Electroacupuncture intervention combined with general anesthesia for
      craniocerebral operations].
AB  - OBJECTIVE: To determine the safety and effectiveness of electroacupuncture (EA)
      intervention combined with general anesthesia (GA) for craniocerebral tumor
      removal surgery involving cerebral eloquent areas. METHODS: A total of 20
      patients with cerebral tumors (durosarcoma, neurogliocytoma, metastatic tumor)
      involving the cerebral eloquent areas were recruited in the present summary. They
      were equally divided into general anesthesia (GA) group and EA + GA group.
      Patients of the EA + GA group were treated with EA stimulation (2 Hz/100 Hz) of
      the bilateral Fengchi (GB 20), Shuaigu (GB 8) and acupuncture stimulation of
      Quanliao (SI 18), Zulinqi (GB 41) and Taichong (LR 3), and not given intubation
      during surgery. Patients of the GA group were treated with intravenous
      administration of Propofol, Fentanyl, Midazolam, Isopropanol, etc. In addition,
      all the patients were given with controlled hypotension by intravenous injection
      of Propofol and Fentanyl. Dosages of Propofol and Sulfentanyl used were recorded.
      Karnofsky performance status scale was used to assess the patient's general well
      being and activities of daily life. RESULTS: The craniocerebral tumor-removal
      surgery was successful in all the 20 patients. Compared with the GA group, the
      dosages of Sulfentanyl and Propofol of the EA+ GA group were significantly lower
      (P < 0.05). No significant difference was found between the GA and EA+ GA groups
      in Karnofsky performance scores (P > 0.05). Patients of the EA+GA group
      experienced successful tumour-removal surgery without trachea cannula, were awake
      and could make a good cooperation with the operator during surgery. They had no
      aggravation of neurofunctional disturbance following the operation. CONCLUSION:
      EA combined with general anesthesia is safe and effective for patients with
      craniocerebral tumor-removal operations involving cerebral eloquent areas.

PMID- 24684106
TI  - [Post-operative management for 86 cases of heart valve replacement surgery
      patients undergoing transcutaneous electrical acupoint stimulation combined with
      general anesthesia].
AB  - OBJECTIVE: To summarize post-operative management strategy for heart valve
      replacement surgery under transcutaneous electrical acupoint stimulation (TEAS)
      combined with general anesthesia. METHODS: From July 2006 to June 2012, a total
      of 86 cases of open-heart surgery patients experiencing TEAS plus general
      anesthesia with cardiopulmonary bypass (heart valve replacement surgery without
      intubation) were recruited in the present summary. Post-operative managements in
      the Intensive Care Unit (ICU) were administrated with strict hemodynamic
      monitoring for volume infusion, routine administration of vasoactive drugs
      (including dopamine and nitroglycerin), oxygen inhalation, and analgesics and
      monitoring of central nervous system and renal function. RESULTS: All the 86
      patients under TEAS + general anesthesia and cardiopulmonary bypass and without
      intubation experienced successful heart valve replacement surgery. The post
      operative pulmonary infection was found in 8 cases (9.30%), the average stay
      duration in ICU was (28.6 +/- 6.2) hours, and the average draining volume of the
      interpleural space was (291 +/- 73)mL. The cardia insufficiency was found in 5
      cases (5.81%), hypoxia occurred in 8 cases (9.30%), nausea in 8 cases (9.30%),
      vomiting 5 cases (5.81%) and post-operative gastrointestinal distension 13 cases
      (15.12%), mild renal insufficiency 3 cases (3.49%), fever (> 38.5 degrees C) 1
      case(1. 16%) and severe post-operative pain 7 cases (8.14%). CONCLUSION: TEAS
      combined with general anesthesia is safe for patients undergoing heart valve
      replacement surgery under cardiopulmonary bypass. The key points of treatment in
      ICU are volume infusion, body temperature maintenance, and pain control.

PMID- 24684107
TI  - [Influence of moxibustion with different duration on colonic epithelial
      structure, serum inflammatory cytokines, and intestinal mucosa inflammatory cell
      signal transduction pathways].
AB  - [ OBJECTIVE: To observe the effect of moxibustion at different duration on
      colonic mucosal morphological chan-ObjectiveTo observe the effect of moxibustion
      at different duration on colonic mucosal morphological changes, serum and colonic
      cytokine levels in ulcerative colitis (UC) rats, so as to provide experimental
      evidence for clinical treat-ges, serum and colonic cytokine levels in ulcerative
      colitis (UC) rats, so as to provide experimental evidence for clinical treatment
      of UC. METHODS: SD rats were randomly divided into blank control, UC model, 3
      cones-moxibustion (3-cones-M), 6-SD rats were randomly divided into blank
      control, UC model, 3 cones-moxibustion (3-cones-M), 6-cones-M and 9-cones-M
      groups, with 6 rats in each group. UC model was established by intra-rectal
      injection of mixture solution ofcones-M and 9-cones-M groups, with 6 rats in each
      group. UC model was established by intra-rectal injection of mixture solution of
      5% trinitro-benzene-sulfonic acid (TNBS, 100 mg/kg) and 50% alcohol (1 1) under
      anesthesia and oral administration of 5%5% trinitro-benzene-sulfonic acid (TNBS,
      100 mg/kg) and 50% alcohol (1 : 1) under anesthesia and oral administration of 5%
      dextran sodium sulfate. Moxibustion (ignited moxa cones) was applied to "Tianshu"
      (ST 25) and "Daheng" (SP 15), once daily indextran sodium sulfate. Moxibustion
      (ignited moxa cones) was applied to "Tianshu" (ST 25) and "Daheng" (SP 15), once
      daily in the first 7 days, and once every other day in the subsequent 14 days.
      Serum IL-8 and IL- 10 contents were assayed by ELISA andthe first 7 days, and
      once every other day in the subsequent 14 days. Serum IL-8 and IL-10 contents
      were assayed by ELISA and colonic toll-like receptor 9 (TLR-9) and nuclear factor
      icB p 65 (NE-KB p 65) protein expression levels detected by Western blot.colonic
      toll-like receptor 9 (TLR-9) and nuclear factor-mB p 65 (NF-mB p 65) protein
      expression levels detected by Western blot. The colonic mucosal structure was
      observed by light microscope after H. E. staining, and by electron microscope,
      respectively.The colonic mucosal structure was observed by light microscope after
      H. E. staining, and by electron microscope, respectively. RESULTS: In comparison
      with the blank control group, the Disease Activity Index (DAI), serum IL-8
      content, colonic TLR-9 andResults - In comparison with the blank control group,
      the Disease Activity Index (DAI), serum IL-8 content, colonic TLR-9 and NE-KB p
      65 protein expression levels were significantly increased in the model group (
      P<0. 05), and serum IL-la content wasNF-mB p 65 protein expression levels were
      significantly increased in the model group ( P < 0.05), and serum IL-10 content
      was notably decreased in the model group (P < 0.05). While in comparison with the
      model group, the DAI, serum IL-8 content, co-notably decreased in the model group
      (P<0.05). While in comparison with the model group, the DAI, serum IL-8 content,
      coIonic TLR-9 and NE-kappaB p 65 protein expression levels in the 3-cones-M, 6
      cones-M and 9-cones-M groups were remarkably down-lonic TLR-9 and NF-mB p 65
      protein expression levels in the 3-cones-M. 6-cones-M and 9-cones-M groups were
      remarkably down- regulated (P < 0.05), and serum IL-10 contents considerably up
      regulated in the three moxibustion groups (P < 0.05). No significant differences
      were found among the three moxibustion groups in the DAI (P > 0.05). The serum IL
      8 contents were significantly lower and serum IL-10 contents were considerably
      higher in the 6-cones-M and 9-cones-M groups than in the 3-cones-M group (P <
      0.05). The changes of colonic TLR-9 and NF-kappaB p 65 protein expression were
      more remarkable in the 9-cones-M group than in the 3-cones-M and 6-cones-M groups
      (P < 0.05). Results of H.E. staining and electron microscopy showed that in the
      model group, mucosal injury, partial disorganization of the glandular organ,
      edema and congestion and inflammatory cell infiltration, mucosal epithelial
      microvili injury with disordered arrangement, etc. under light microscope, and
      local mucosal defect, apoptotic bodies and mucolysis under electron microscope
      were found, these situations were obviously lighter in rats of the three
      moxibustion groups, particularly in the 9-cones-M group. CONCLUSION: Moxibustion
      intervention can relieve colonic mucosal injury in UC mice, which may be closely
      associated with its effects in suppressing serum proinflammatory cytokine IL-8,
      up-regulating anti-inflammatory cytokine IL-10 level, and inhibiting colonic NF-
      KB p 65 and TLR-9 protein expression, and the effects of longer duration of
      moxibustion are better.

PMID- 24684108
TI  - [Effect of electroacupuncture intervention on enteric microecology in ulcerative
      colitis rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on enteric microbial
      populations in ulcerative colitis (UC) model rats, so as to study its mechanisms
      underlying improving UC. METHODS: Thirty-nine male SD rats were randomly divided
      into control group, model group and EA group (n = 13 in each group). The UC model
      was established by intragstric perfusion of 4% dextran sodiumaqueous solution
      (DSS), once daily for 7 days. EA (15-25 Hz, 0.1 mA) was applied to bilateral
      "Tianshu" (ST 25), "Zusanli" (ST 36) and "Shangjuxu" (ST 37) for 10 min, once
      daily for 5 days. Disease Activity Index (DAI) including body weight and stool
      blood state was used to evaluate the animals' conditions. The rats' excrement was
      collected to detect the abundance and diversity of bacterial populations by
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE).
      RESULTS: In comparison with the control group, the animals' DAI score and enteric
      Clostridium bifermentans content were significantly increased (P < 0.05), and the
      abundance and diversity of bacterial populations, and contents of enteric
      Lachnospiraceae bacterium and Lactobacillus sp. were considerably down-regulated
      in the model group (P < 0.05, P < 0.01). Compared with the model group, the DAI
      score and enteric Clostridium bifermentans content were significantly lowered,
      and the abundance and diversity of bacterial populations, and contents of enteric
      Lachnospiraceae bacterium and Lactobacillus sp. were notably increased in the EA
      group (P < 0.05, P < 0.01). CONCLUSION: EA can improve DAI and the abundance and
      diversity of enteric bacterial microbiota in UC rats, which may be related to its
      protective effect on enteric microecology in UC.

PMID- 24684109
TI  - [Effect of acupoint catgut-embedding therapy on changes of structure of
      hippocampal neurons in senile chronic stress rats].
AB  - OBJECTIVE: To observe the effect of chronic stress stimulation on aging and the
      effect of acupoint catgut-embedding therapy on structural changes of hippocampal
      pyramidal neurons in senile chronic stress rats, so as to reveal its mechanisms
      underlying resisting senility. METHODS: Forty-eight male SD rats were randomly
      divided into normal control, senility model, senility + stress and senility +
      stress + catgut-embedding (catgut-embedding) groups (n = 12 in each group).
      Senility model was established by intraperitoneal injection of D-galactose
      liquor, once daily for 8 weeks; and chronic stress was produced by restricting
      the rat in an inmovable cylinder for 1-4 h progressively, once daily for 4 weeks.
      Catgut embedment (0.4-0.6 cm in length) was applied to "Baihui" (GV 20) and
      "Shenshu" (BL 23), "Neiguan" (PC 6) and "Ganshu" (BL 18) alternatively by using a
      surgical needle, once a week, 8 weeks altogether. The brain tissue containing
      hippocampus was cut into sections to be stained with H.E. technique, and the
      number of the hippocampal pyramidal neurons of CA 3 region was counted under
      optical microscope. The ultrastructure of pyramidal neurons in the left CA 3
      region of the hippocampus was observed by electron microscope (2 rats for each
      group). RESULTS: Compared with the normal control group, the numbers of
      hippocampal pyramidal neurons in the senility model group and senility + stress
      group were remarkably decreased (P < 0.05, P < 0.01). The number of pyramidal
      neurons was obviously fewer in the senility + stress group than in the senility
      model group (P < 0.01). In comparison with the senility + stress group, the
      number of pyramidal neurons in the catgut-embedding group was considerably
      increased (P < 0.01). Results of optical microscope showed that the pyramidal
      cells were sparse in the senility model and very sparse in the senility + stress
      group, and relatively richer in the catgut-embedding group. Findings of the
      electron microscope displayed that the pyramidal neurons presented an injured
      state including shrank soma, pyknosis of the cellular nucleus, atrophia of
      nucleoli, onglobation of intranuclear caryotin, decreased glycogen granules, etc.
      in the senility model group, and an extremely irregular shape, partial apoptosis,
      severer pyknosis of the cellular nucleus, more edema blank regions, etc. in the
      senility + stress group. These situations of pyramidal cells in the hippocampal
      CA 3 region were relatively milder in the catgut-embedding group. CONCLUSION:
      Chronic stress may aggravate the damage of hippocampal pyramidal neurons in
      senile rats, which can be improved by catgut-embedding therapy.

PMID- 24684110
TI  - [Effects of electroacupuncture intervention combined with polysaccharide of
      Gastrodia elata Blume on expression of nestin and cytokines of neural stem cells
      in the dentate gyrus of cerebral ischemia rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui" (GV 20)
      and "Zusanli" (ST 36) and EA plus polysaccharide of Gastrodia elata Blume (PGB)
      on neural stem cell (NSC) proliferation in cerebral ischemia (CI) rats, so as to
      explore its mechanisms underlying improvement of CI. METHODS: A total of 40 SD
      rats were randomly divided into normal control, CI model, EA , medication (PGB)
      and EA + medication groups (n = 8 in each group). The CI model was established by
      occlusion of the middle cerebral artery (MCAO). Two weeks after modeling, rats of
      the medication and EA + medication groups were administrated with PGB (100 mg/kg)
      once daily for 2 successive weeks. EA (2 Hz, 3 V) was applied to "Baihui" (GV 20)
      and left "Zusanli" (ST 36) for 30 min, once daily for 2 weeks. The expression of
      Nestin and stem cell factor (SCF) proteins in the dentate gyrus (DG) of
      hippocampus was detected by immunohistochemistry. RESULTS: Compared with the
      normal control group, the expression of Nestin and SCF proteins in the
      suprapyramidal blade (SPB) and infrapyramidal blade (IPB) of DG were
      significantly increased in the model group (P < 0.05). After EA intervention, the
      expression levels of Nestin and SCF of SPB and IPB of DG were considerably
      further up-regulated in both EA group and EA + medication group (P < 0.05), and
      the effect of EA + medication group was significantly superior to that of simple
      EA group and medication group (P < 0.05). CONCLUSION: EA combined with PGB can
      significantly up-regulate the expression of Nestin and SCF in the hippocampal DG
      in CI rats, and its effects are apparently superior to those of simple EA or
      simple medication. It suggests that EA-induced proliferation of SCF may be one of
      the mechanisms underlying relieving CI.

PMID- 24684111
TI  - [Effects of electroacupuncture intervention on expression of hypothalamic PI 3 K
      and p-PI 3 K Proteins in insulin resistance model rats].
AB  - OBJECTIVE: To observe the effect of "Shuanggu Yitong" (Double-reinforcing and one
      unblocking) needling [electroacupuncture (EA) of "Guanyuan" (CV 4), "Housanli"
      (ST 36), "Fenglong" (ST 40) and "Zhongwan" (CV 12)] on expression of hypothalamic
      phosphatidylinositol 3-kinase (PI 3 K) and p-PI 3 K proteins in insulin
      resistance rats. METHODS: Sixty Wistar rats were randomized into normal control,
      model, EA prevention, EA, cerebrospinal fluid (CSF), and Wortmannin (PI 3 K
      antagonist) groups (n = 10 rats/group). Insulin resistance model was established
      by feeding the animal with high fat forage continuously for 8 weeks. For rats of
      the EA group, EA (2 Hz, 1 mA) was applied to ipsilateral "Housanli"(ST 36)
      "Fenglong" (ST 40), and "Guanyuan" (CV 4)-"Zhongwan" (CV 12) for 15 min, once
      daily, 5 times a week and for 8 weeks, beginning after modeling. For rats of the
      EA prevention group, EA was conducted simultaneously with the modeling. For rats
      of the Wortmannin group and CSF group, cerebroventricular microinjection of
      Wortmannin (50 nmol/L, 3 mg/kg) or artificial CSF was given through an implanted
      steel cannel. Fasting plasma glucose (FPG) and fasting serum insulin (FINS)
      contents were assayed using glucose-tested instrument and ELISA respectively,
      insulin activity index (IAI) was calculated [IAI = Ln (1/FPG x FINS)], and the
      expres- sion of hypothalamic PI 3 K and p-PI 3 K proteins was detected by Western
      blot. RESULTS: In comparison with the normal control group, the body weight (BW),
      FPG and FINS contents at time-points of 8 and 16 weeks were considerably
      increased (P < 0.01), and IAI, hypothalamic PI 3 Kp 110 and p-PI 3 Kp 110 protein
      expression levels were obviously decreased in the model group (P < 0.01).
      Compared with the model group, the FPG and FINS contents at the 8th week after
      modeling in the EA prevention group, the BW and FPG levels at the 16th week in
      the EA prevention, EA and CSF groups, FINS levels at the 16th week in the EA
      prevention and EA groups were remarkably decreased (P<0.05, P<0.01), IAI, and
      hypothalamic PI 3 Kp 110 and p-PI 3 Kp 110 protein expression levels were
      significantly up-regulated in the EA prevention, EA and CSF groups (P < 0.05, P <
      0.01). No significant differences were found among the EA prevention, EA and CSF
      groups, and between the model and Wortmannin groups in the BW, FPG, FINS, IAI and
      hypothalamic PI 3 Kp 110 and p-PI 3 Kp 110 expression levels (P > 0.05).
      CONCLUSION: EA intervention can reduce insulin resistance by suppressing the
      increase of body weight, blood glucose and insulin contents, and increasing
      hypothalamic PI 3 K expression levels in insulin resistance rats.

PMID- 24684112
TI  - [Effects of acupuncture stimulation of different acupoint groups on sleeping
      duration and serum and striatal dopamine contents in rats with gastric mucosal
      injury].
AB  - OBJECTIVE: To observe the effect of acupuncture intervention on gastric ulcer
      (GU) and sleeping quality from the viewpoint of brain-gut axis which plays an
      important role in the regulation of many vital functions in health and disease.
      METHODS: Forty male Wistar rats were randomized into normal control, GU model,
      acupuncture of "Zhongwan" (CV 12)-"Zusanli" (ST 36, gastric treatment acupoints),
      acupuncture of "Shenmai" (BL 62)-"Zhaohai" (KI 6, sleep-promotion acupoints), and
      acupuncture of CV 12-ST 36-BL 62-KI 6 (combined treatment) groups, with 8 rats in
      each group. GU model was established by intragastric perfusion of dehydrated
      alcohol (1 mL/rat), and sleep model established by intraperitoneal injection of
      pentobarbital sodium (40 mg/kg) after the last treatment. The abovementioned
      acupoints were punctured with filiform needles and stimulated by manipulating the
      needle for about 30 s, once every 5 mm during 20 mm of needle retention. The
      treatment was conducted once daily for five days. Gastric mucosal lesion index
      was assessed by Guth's method, and the mucosal pathological changes were observed
      under microscope after H. E. staining. The contents of dopamine (DA) in the serum
      and striatal tissues were detected by ELISA kit. RESULTS: Compared with the
      normal control group, the rats' sleeping duration, and serum DA content were
      markedly decreased and the gastric mucosal lesion index, and the striatal DA
      content remarkably increased in the model group (P < 0.01). In comparison with
      the model group, the rats' sleeping duration, and serum DA content were
      significantly increased, and the gastric mucosal lesion index, and the striatal
      DA content remarkably down-regulated in the CV 12-ST 36 (gastric treatment
      acupoints), BL 62-KI 6 (sleep-promotion acupoints) and CV 12-ST 36-BL 62-KI 6
      (combined treatment) groups (P < 0.05, P < 0.01). The effects of the combined
      treatment group were notably superior to those of the sleep promotion acupoints
      group in reducing mucosal lesion index and in increasing serum DA level (P <
      0.01, P < 0.05). CONCLUSION: Acupuncture stimulation of "Zhongwan" (CV 12),
      "Zusanli" (ST 36), "Zhaohai" (KI 6) and "Shenmai" (BL 62) can relieve the gastric
      mucosal lesion, and prolong the sleeping duration in gastric lesion rats, which
      may be related to its effects in increasing blood DA and lowering striatal DA
      level, suggesting a correlation between the gastrointestinal disorders and
      sleeping.

PMID- 24684113
TI  - [Effects of grain-sized moxibustion on learning and memory ability and amyloid
      deposition of transgenic Alzheimer's disease mice].
AB  - OBJECTIVE: To observe the effect of grain-sized moxibustion at "Xinshu" (BL 15)
      and "Shenshu" (BL 23) on memory-learning ability and amyloid deposition in
      transgenic Alzheimer's disease (AD) mice. METHODS: seventeen amyloid precursor
      protein (APP)/presenilin (PS)1 (APP+/PS 1+) double transgenic 6799 mice aged 3-4
      weeks were randomly divided into model group (n = 9) and moxibustion group (n =
      8). Nine wide-type (C 57 BL/6 J) female mice were used as the normal control
      group. Moxibustion (ignited grain-sized moxa cone) was applied to bilateral
      "Xinshu" (BL 15) and "Shenshu" (BL 23) for about 30 s, once a day for 9 courses
      (10 days constitute a therapeutic course, with 2 days' break between every two
      courses). Morris water maze tests were performed to detect the mice's learning
      memory ability. The alterations of beta-amyloid deposition (number of the
      positive plaques) in the cerebral cortex and hippocampus were detected by using
      an imaging analysis system following Congo red staining of the cerebral tissue
      sections. RESULTS: Compared with the normal group, the average escape latency of
      place navigation tests was significantly increased (P < 0.05), and the target
      platform crossing times and percentage of dwell time in the target quadrant of
      the spatial exploring tests were notably decreased in the model group (P < 0.05).
      After moxibustion intervention, the escape latency was remarkably shortened, and
      the target-platform crossing times and dwell time percentage were obviously
      increased in the moxibustion group in comparison with the model group (P < 0.05),
      suggesting an improvement of the learning-memory ability after moxibustion.
      Results of Congo red staining of the cerebral tissue showed that there were many
      irregular, uneven staining positive plaques in the cerebral cortex and
      hippocampus of AD mice in the model group. Compared with the model group, the
      positive plaque numbers in both cerebral cortex and hippocampus were considerably
      reduced in the moxibustion group (P < 0.05). CONCLUSION: Grain-sized moxibustion
      at "Xinshu" (BL 15) and "Shenshu" (BL 23) can ameliorate learning-memory ability
      and restrain the formation of amyloid deposition in AD mice.

PMID- 24684114
TI  - [Effects of mild moxibustion intervention on serum and liver amyloid-A protein,
      serum IL-6, TNF-alpha and IL-10 contents in atherosclerosis rabbits].
AB  - OBJECTIVE: To observe the effect of mild-moxibustion on serum amyloid-A (SAA)
      protein, cytokine contents and liver amyloid-A protein expression in
      atherosclerosis rabbits, so as to explore its anti-inflammation mechanism.
      METHODS: A total of 40 Japanese male rabbits were equally randomized into normal
      control, model, mild moxibustion and medication (lovastatin) groups. The
      atherosclerosis model was established by feeding the animals with high-fat diet
      for 14 weeks and intravenous injection of bovine serum albumin (250 mg/kg, once
      every week, 3 times altogether). Mild moxibustion was applied to "Shenque" (CV
      8), "Housanli" (ST 36) for 10 min, once daily for 14 weeks beginning from the
      first day of modeling. The SAA, serum IL-6, TNF-alpha and IL-10 contents were
      determined by double antibody sandwich method, and liver amyloid-A protein
      expression was detected by Western blot. The pathological changes of the cervical
      common artery were detected by H. E. staining. RESULTS: In comparison with the
      normal control group, SAA, serum IL-6, IL-10 and TNF-alpha contents and liver
      amyloid-A protein expression level were significantly increased in the model
      group (P < 0.01, P < 0.05). Compared to the model group, SAA, serum IL-6 and TNF
      alpha contents, and liver amyloid-A protein expression level were considerably
      down-regulated and serum IL-10 content was obviously up-regulated in the
      moxibustion and medication groups (P < 0.05, P < 0.01). No significant
      differences were found between the moxibustion and medication groups in the five
      indexes (P > 0.05). In addition, the pathological changes of the cervical common
      arterial endomembrane in the moxibustion and medication group were relatively
      milder, suggesting a protective effect of moxibustion on liver tissue in
      atherosclerosis rabbits. CONCLUSION: Mild moxibustion can relieve liver injury in
      atherosclerosis rabbits, which is associated with its effects in suppressing
      serum inflammatory cytokines and liver amyloid-A protein expression and up
      regulating anti-inflammatory cytokine IL-10 level.

PMID- 24684115
TI  - [Effect of acupotomy intervention on cervicomuscular apoptosis in cervical
      spondylosis rabbits].
AB  - OBJECTIVE: To observe the effect of acupotomy therapy on cervicomuscular
      apoptosis and apoptosis regulator Bax protein expression in cervical spondylosis
      (CS) rabbits so as to investigate its mechanisms underlying improvement of CS.
      METHODS: Twenty-four New Zealand rabbits were randomly divided into normal
      control, model, acupotomy and electroacupuncture (EA) groups, with 6 rabbits in
      each group. The CS model was made by forced head-bowing for 5 hours in a
      restrained chamber, once daily for 12 weeks. Acupotomy was performed at the
      starting point of trapezius, the mastoid process attaching point of
      sternocleidomastoid, the cerverical vertebrae joint process or the local
      induration or cord-like mass (2 or 3 points of them were used as the needle-knife
      entering points), once a week for 3 weeks. For animals of the EA group, EA (2
      Hz/100 Hz, 2 mA) was applied to bilateral "Tianzhu" (BL 10), "Jingbailao" (EX-HN
      15), "Dazhu" (BL 11) for 20 min, once daily and 3 times a week for 3 weeks. The
      number of apoptotic cells in the cervical muscle was observed by light microscope
      after TUNEL staining and muscular Bcl-2 and Bax protein expression was detected
      by Western blot. RESULTS: In comparison with the control group, the number of
      cervicomuscular apoptotic cells, and the expression level of cervicomuscular Bax
      protein were significantly increased, and the Bcl-2/Bax was obviously decreased
      in the model group (P < 0.01, P < 0.05). Compared to the model group, the number
      of apoptotic cells and the expression level of muscular Bax protein were notably
      decreased in the acupotomy group (P < 0.01, P < 0.05), while the ratio of Bcl-2
      and Bax was apparently increased in the acupotomy group (P < 0.05). The effects
      of acupotomy were significantly superior to those of EA in lowering apoptotic
      cell number and in up-regulating Bcl-2/Bax (P < 0.01, P < 0.05). No significant
      differences were found between the EA and model groups in the apoptotic cell
      number and among the four groups in Bcl-2 protein expression levels (P > 0.05).
      CONCLUSION: Acupotomy therapy can reduce cervicomuscular cellular apoptosis and
      Bax protein expression in CS rabbits, which may be one of its mechanism
      underlying improving CS.

PMID- 24684116
TI  - [Progress of researches on mechanisms of acupuncture therapy underlying improving
      myocardial ischemia and the future approach for in-depth study on its mechanisms
      from epigenetics].
AB  - As an important content of alternative and complementary medicine, acupuncture
      therapy has been proved to be effective in relieving myocardial ischemia (MI).
      Authors of the present paper review recent progress of researches on acupuncture
      therapy in resisting MI from 1) improving cardiovascular function and promoting
      angiogenesis, and 2) protecting myocardial cells from further injury and reducing
      cellular apoptosis at different pathological stages of MI. Moreover, the authors
      discuss the characteristics of epigenetic regulation in the process of MI and
      cardiac repair including the methylating of DNA, modification of histone,
      remodeling of the chromatin, and micro-RNA expression, mediating cellular
      apoptosis, regeneration of myocardial blood vessels, etc. The authors hold that
      future studies on the underlying mechanisms of acupuncture therapy in the
      prevention and treatment of MI from epigenetics may be a new approach and a new
      direction.

PMID- 24684117
TI  - [Toll-like receptor 4 in regional acupoints and initiation of acupuncture
      signals].
AB  - It has been well documented that acupuncture effect is produced through suitable
      manipulation stimulation of the inserted acupuncture needle, and subsequent
      activation of the body' s inherent nerve-endocrine-immune regulating network. As
      a physical stimulus, the acupuncture stimulation exerted onto the local acupoint
      needs being converted into biological signal first, further reaching favorable
      regulation in the body. Toll-like receptor 4 (TLR 4), an important molecular
      pattern recognition receptor, can not only recognize the exogenous pathogen
      associated molecular patterns but also identify endogenous damage-associated
      molecular patterns, leading to activation of innate immunity. What's more, TLR 4
      has a close relationship with nervous and immune system of the body. In the
      present paper, the authors make a discussion on the correlation between TLR 4 and
      acupuncture intervention from 1) TLR 4 and acupuncture signal conversion, 2) TLR
      4 and acupuncture clinical phenomenon, and 3) TLR 4 and related mechanisms of
      acupuncture intervention. Moreover, the authors also think that TLR 4 in the
      acupoint area may participate in the initiation process of acupuncture
      stimulation information.

PMID- 24684118
TI  - [Progress of studies on mechanisms of acupuncture underlying regulation of
      cardiac function via autonomic nervous system].
AB  - Acupuncture therapy has been confirmed to be effective in treating cardiovascular
      diseases in clinical practice. Acupuncture-induced balance of the autonomic
      nervous system activities is one of its key mechanisms. In the present paper, the
      authors review progress of studies on acupuncture treatment of cardiovascular
      diseases from 1) regulating cardiac sympathetic-beta-adrenergic receptor activity
      and myocardial intracellular GTP-binding protein (Gs)-adenylylcyclase (AC)-cyclic
      adenosine monophosphate (cAMP)-protein kinase (PKA) signaling, and 2) balancing
      cardiac sympathetic and vagal nerve activities. Due to limited experimental
      conditions, in-depth studies about the mechanisms of acupuncture intervention
      underlying improvement of cardiovascular functions are relatively fewer up to
      now. Along with the further development of modern biology, the mechanism of
      acupuncture intervention underlying regulation of cardiac function via autonomic
      nerve system will be revealed in detail.

PMID- 24684119
TI  - Maternal mortality ratio in Lebanon in 2008: a hospital-based reproductive age
      mortality study (RAMOS).
AB  - INTRODUCTION AND OBJECTIVES: International agencies have recently assigned
      Lebanon to the group H of countries with "no national data on maternal
      mortality," and estimated a corresponding maternal mortality ratio (MMR) of 150
      per 100,000 live births. The Ministry of Public Health addressed the discrepancy
      perceived between the reality of the maternal mortality ratio experience in
      Lebanon and the international report by facilitating a hospital-based
      reproductive age mortality study, sponsored by the World Health Organization
      Representative Office in Lebanon, aiming at providing an accurate estimate of a
      maternal mortality ratio for 2008. The survey allowed a detailed analysis of
      maternal causes of deaths. METHODS: Reproductive age deaths (15-49 years) were
      initially identified through hospital records. A trained MD traveled to each
      hospital to ascertain whether recorded deaths were in fact maternal deaths or
      not. ICD10 codes were provided by the medical controller for each confirmed
      maternal deaths. RESULTS: There were 384 RA death cases, of which 13 were
      confirmed maternal deaths (339%) (numerator). In 2008, there were 84823 live
      births in Lebanon (denominator). The MMR in Lebanon in 2008 was thus officially
      estimated at 23/100,000 live births, with an "uncertainty range" from 153 to
      30.6. Hemorrhage was the leading cause of death, with double the frequency of all
      other causes (pregnancy-induced hypertension, eclampsia, infection, and
      embolism). CONCLUSION: This specific enquiry responded to a punctual need to
      correct a clearly inadequate report, and it should be relayed by an on-going
      valid surveillance system. Results indicate that special attention has to be
      devoted to the management of peri-partum hemorrhage cases. KEYWORDS: Arab,
      postpartum hemorrhage, development, pregnancy management, verbal autopsy

PMID- 24684120
TI  - [Acquired pediatric cholesteatoma: predictive factors of recurrence. A
      retrospective study of 11 years].
AB  - AIM OF THE STUDY: To define the predictive factors of recurrence of the pediatric
      acquired cholesteatoma in order to improve the long-term results, to restore a
      good hearing function and to prevent the complications. PATIENTS AND METHODS: A
      retrospective study concerning all cases of pediatric acquired cholesteatoma,
      treated during the period 1997-2008 in our center, and followed up for at least
      one year. A description of the parameters concerning the patients, disease and
      treatment as well as a univariate analysis were undertaken in order to determine
      the recurrence predictors. The recurrence-free survival was calculated using the
      Kaplan-Meier method. RESULTS: 26 ears were studied and followed over a mean
      period of 62 months after the first intervention. The mean age was 12 years (11.7
      years) with a 2.7 sex-ratio. The main clinical presentations were otorrhea (65%)
      and hypoacusia in 42% of cases. Fifteen cases (57.7%) presented an extension to
      the mastoid, 50% of the ears had an ossicular erosion and 11 cholesteatomas
      revealed a local or regional invasion. Almost 3/4 (73%) of the cholesteatomas
      were treated using a canal wall up surgery. The cumulative rate of recurrence was
      53.8% and the rate of recurrence-free survival was 84%, 56%, and 44.7% at 12, 24
      and 36 months respectively. Only the extension of the cholesteatoma to the
      mastoid, and the local and regional invasion (sinus tympani, lateral semi
      circular canal, facial nerve recess, etc.) of the cholesteatoma at diagnosis,
      showed a significant higher risk of recurrence (p < 0.05). CONCLUSION: In our
      study, the extent of the disease at diagnosis is considered as the major
      predictive factor of recurrence in pediatric acquired cholesteatoma population
      raising the problem of delayed diagnosis.

PMID- 24684121
TI  - Impact of breast vs. formula feeding mode on primary teeth lead level.
      Retrospective clinical study and literature review.
AB  - Lead exposure is a global environmental problem inducing lifelong adverse health
      effects. Children's exposure to lead, from birth to 6 months, is typically
      dominated by dietary sources. The first primary mandibular molar could provide an
      integrated record of lead exposure. The aim of this study is to detect the level
      of lead in the first primary molar of a group of Lebanese children born between
      1990 and 2000, living in Beirut and suburbs, and to compare the amount of lead
      according to gender and feeding mode. MATERIALS AND METHODS: A group of 53 first
      primary molars belonging to 53 Lebanese children (31 girls and 22 boys), and aged
      9 to 12 years old, were included in the study. The primary outcome variable of
      the study was the amount of lead level (mg/kg) in the first primary mandibular
      molars taken at the time of the natural exfoliation and measured by ICP/MS
      (Inductively Coupled Plasma Mass Spectrometry). Children included in the study
      were fed exclusively with formula feeding or maternal feeding for six months.
      RESULTS: The mean lead level of the first primary molar was 0.678 mg/kg +/-
      0.717. The mean lead was significantly higher among children fed with instant
      formula milk (0.876 +/- 0.802) than breastfed children (0.455 +/- 0.540), (p =
      0.044). No significant difference was found between girls (0.595 < or = 0.548)
      and boys (0.794 +/- 0.905), (p = 0.440). CONCLUSION: Within the limitations of
      this study, we found a statistically significant difference in the teeth lead
      level between breastfeeding and formula feeding, in favor of breastfeeding. This
      difference proves once more the importance of breastfeeding ; on the other hand,
      the Lebanese children accumulated lead in their teeth to levels below the
      international levels.

PMID- 24684122
TI  - Comparison of quality of life in a group of Lebanese type 1 diabetics on insulin
      pump and those on multiple daily injections.
AB  - AIM: The aim of the study is to investigate the differences in the quality of
      life (QOL) in Lebanese youths with type 1 diabetes using continuous subcutaneous
      insulin infusion (CSII) and those using multiple daily injections (MDI) treatment
      modalities. METHODS: A descriptive, cross-sectional, comparative matched design
      was used. The sample included 36 adolescents and young adults on one of two
      treatment modalities (CSII or MDI) and matched for age, gender, and level of
      education. QOL was measured with the Indiana Diabetes Quality of Life for Youth
      and latest HbA1C level was recorded. RESULTS: The CSII group had significantly
      lower HbA1C levels (p < 0.001), and reported better health perception (p =
      0.029), more satisfaction with life (p = 0.002), less impact of the disease (p =
      0.002), and fewer worries about their disease (p = 0.029), compared to the MDI
      group. The overall quality of life score was also significantly better in the
      CSII group than in the MDI group (p = 0.001). CONCLUSIONS: Findings suggest that
      CSII is associated with better glycemic control and QOL in the Lebanese youth
      population with type 1 diabetes.

PMID- 24684123
TI  - The prevalence of endocrinopathies among Lebanese women presenting with hirsutism
      to an endocrine clinic.
AB  - Hirsutism is a common condition in women characterized by excessive growth of
      terminal hair in a male pattern distribution. It may be a manifestation of
      underlying pathologies. Since there is no data published about the prevalence of
      endocrinopathies among hirsute women in Lebanon, this study's aim was to reveal
      the most common etiologies of hirsutism in this population. METHODS: The study is
      a descriptive review of cases of 160 females with hirsutism presenting to a
      single endocrinologist clinic. Data about history, physical exam, blood tests and
      imaging results were collected after review of medical charts. RESULTS: Out of
      the 160 cases reviewed, 14 females (8.8%) were left undiagnosed. Out of 146
      subjects diagnosed, 72.6% were found to have polycystic ovary syndrome (PCOS),
      18.5% idiopathic hirsutism (IH), 4.6% non-classic congenital adrenal hyperplasia,
      2.6% hyperprolactinemia, 0.6% Cushing's syndrome and 0.6% hypothyroidism. A
      higher percentage of irregular menses and a trend for overweight were found among
      the PCOS group. CONCLUSIONS: PCOS remains the most common cause of hirsutism in
      an endocrine referral clinic, similar to other populations. A low threshold for
      diagnostic workup is in order, especially when there is associated menstrual
      irregularity or overweight.

PMID- 24684124
TI  - Observations on the Ministry of Public Health program of support to the
      hospitalization of patients in Lebanon.
AB  - Lebanon has a highly fragmented health care system. The Lebanese population
      receives its health care services through a system dominated by the private
      sector that is dependent to a large extent on public sector financing. Lebanon
      spends about 83% of its Gross Domestic Product (GDP) on health. This study
      consists of observations on the utilization of the Ministry of Public Health
      (MOH) program of hospital care provision. The study population included all
      patients admitted for hospitalization in any of the 126 hospitals contracted with
      the MOH, between August 2008 and July 2009 (one full year). This review is
      limited to medical admissions only. The surgical admissions have been excluded
      since they are covered under a 'flat fee' reimbursement. Findings reveal that a
      significant proportion of the hospital admissions under this program are for
      conditions that may not need hospitalization. Moreover, most of these admissions
      receive care in relatively small and peripheral hospitals. The findings ought to
      lead to a further scrutiny of the ministry program of support to the
      hospitalization of its nationals. Measures may be indicated to improve the
      efficiency and effectiveness of hospital utilization, avoid waste and possibly
      fraud, and reconsider the role of small and peripheral hospitals within the
      health care system of the country.

PMID- 24684125
TI  - The Lebanese Society for Infectious Diseases and Clinical Microbiology (LSIDCM)
      guidelines for adult community-acquired pneumonia (Cap) in Lebanon.
AB  - Adult community-acquired pneumonia (CAP) is a common cause of morbidity and
      mortality which is managed by different disciplines in a heterogeneous fashion.
      Development of consensus guidelines to standardize these wide variations in care
      has become a prime objective. The Lebanese Society of Infectious Diseases and
      Clinical Microbiology (LSIDCM) convened to set Lebanese national guidelines for
      the management of CAP since it is a major and a prevalent disease affecting the
      Lebanese population. These guidelines, besides being helpful in direct clinical
      practice, play a major role in establishing stewardship programs in hospitals in
      an effort to contain antimicrobial resistance on the national level. These
      guidelines are intended for primary care practitioners and emergency medicine
      physicians. They constitute an appropriate starting point for specialists'
      consultation being based on the available local epidemiological and resistance
      data. This document includes the following: 1/ Rationale and scope of the
      guidelines; 2/ Microbiology of CAP based on Lebanese data; 3/ Clinical
      presentation and diagnostic workup of CAP; 4/ Management and prevention
      strategies based on the IDSA/ATS Consensus Guidelines, 2007, and the ESCMID
      Guidelines, 2011, and tailored to the microbiological data in Lebanon; 5/
      Comparison to regional guidelines. The recommendations made in this document were
      graded based on the strength of the evidence as in the 2007 IDSA/ATS Consensus
      Guidelines. Hopefully, these guidelines will be an important step towards
      standardization of CAP care in Lebanon and set the agenda for further research in
      this area.

PMID- 24684127
TI  - Rapid and sustained recovery of renal function with transient placement of an
      intrauretral nephrostomy catheter in an infant with ureteropelvic junction
      obstruction and acute renal failure.
AB  - Ureteropelvic junction obstruction (UPJO) is a common, congenital urinary
      malformation in the pediatric age group. In most cases the diagnosis is made
      antenataly and resolves spontaneously. Postnatal diagnosis is made when symptoms
      of urinary tract infection or abdominal pain occur. We report a six-month-old
      girl with single kidney and known vesicoureteral reflux grade IV presenting with
      severe acute renal failure (ARF), requiring acute peritoneal dialysis (PD).After
      diagnosis of decompensated UPJO, a nephrostomy was performed, and renal function
      restored within seven days. UPJO was subsequently treated by open pyeloplasty. To
      our knowledge, this is the first case of UPJO requiring PD due to severe renal
      failure in a child. Children with UPJO and major morbidity of the contralateral
      kidney are at risk of renal failure and should therefore be followed carefully to
      prevent serious complications.

PMID- 24684126
TI  - Idiopathic retroperitoneal fibrosis presenting as recurrent scrotal edema: Report
      of a case and review of the literature.
AB  - Primary or idiopathic retroperitoneal fibrosis, first described by Ormond in
      1948, is a rare and elusive diagnosis, requiring a high level of suspicion.
      Patients usually present with entrapment of retroperitoneal organs, the most
      common being the ureters, causing hydronephrosis and acute kidney injury. Here,
      we present the case of a 56-year-old male presenting for recurrent and
      intermittent scrotal edema. Upon routine laboratory workup, he was found to have
      an elevated creatinine level. Imaging showed encasement of bilateral ureters.
      Bilateral ureteral stents were placed with relief of his obstructive uropathy,
      followed by normalization of creatinine. The patient later underwent laparoscopic
      release of retroperitoneal adhesions. Biopsies taken from the operative site
      showed fibroblast proliferation and elements of acute and chronic inflammation.
      With further workup of etiologies being negative, he was diagnosed with
      idiopathic retroperitoneal fibrosis.

PMID- 24684128
TI  - Remission of central fever with morphine post traumatic brain injury.
AB  - After a brain injury, raised temperature may be due to a regulated readjustment
      in the hypothalamic 'set-point' in response to inflammation. The purpose of this
      report is to mention possible implications related to temperature and homeostasis
      of morphine treatment in a patient with brain injury. During the month previous
      to her hospitalization in our city she was treated for fever with paracetamol and
      metamizol without results. After 31 days with similar results, we changed to
      morphine IV considering the possibility of treating pain and fever. This option
      was successful and afterwards we changed to fentanyl patches, keeping fever
      absent. After 100 days of hospitalization, the patient was discharged to her
      home.

PMID- 24684129
TI  - [Continuing education and the image of dentists].

PMID- 24684130
TI  - [Zirconium or zirconium oxide/zirconium dioxide?].

PMID- 24684131
TI  - [Correction: A patient with Noonan syndrome].

PMID- 24684132
TI  - [Throat ache ans swelling of the neck: first symptoms of Lemierre's syndrome].
AB  - Lemierre's syndrome, a thrombophlebitis of the internal jugular vein, is a rare
      disorder, usually caused by the microorganism Fusobacterium necrophorum. Throat
      ache and swelling of the neck are often the first symptoms. Without adequate
      treatment, Lemierre's syndrome may result in thrombosis of the internal jugular
      vein and metastatic lung abscesses, with a mortality rate of 18%. On the basis of
      2 cases, Lemierre's syndrome is described here. In cases where Lemierre's
      syndrome is suspected, hospitalization often follows, with the administration of
      intravenous antibiotics and drainage of the abscesses. One should be on the alert
      for Lemierre's syndrome when a patient is presented with swelling in the neck
      following an oropharyngeal infection.

PMID- 24684133
TI  - [Dentistry and healthcare legislation 10. The law governing complaints: readily
      accessible filing procedures].
AB  - The law promises patients a readily accessible means of filing complaints.
      Healthcare providers are therefore required to adopt regulations governing
      complaints which satisfy a number of conditions. Most dentists choose to adopt
      the regulations which have been established by their professional organization.
      In addition to handling complaints, there is also a provision for mediation,
      which is often used by patients. Mediation appears, then, to be a successful
      provision. Many complaints have their origin in insufficient knowledge of
      healthcare legislation and patients' rights legislation. This demonstrates that
      more attention should be given to these subjects in educational programmes and
      programmes in continuing education. The present law governing complaints is
      expected to be replaced this year by a new, more comprehensive law in which
      considerable attention will be devoted to the quality of care as well as to
      complaints. It seems likely, however, that the new law governing complaints will
      damage the effective manner in which patients' complaints are dealt with in
      dentistry today.

PMID- 24684134
TI  - [Facial ageing and cosmetic facial surgery].
AB  - The aim of cosmetic facial surgery is to enhance facial beauty by reducing the
      effects of ageing or by beautifying certain aspects of the face. The face can be
      subdivided anatomically into the skin, the fat compartments, the ligaments (the
      links between the skin and the underlying facial skeleton), the superficial
      musculoaponeurotic system and the masticatory and mimic musculature. As a result
      of the influence of gravity and ageing, changes which progress according to a
      fixed pattern take place at all levels of the soft tissue of the face. The
      supporting facial skeleton also reduces in volume in a characteristic manner. A
      thorough knowledge of the facial anatomy and the ageing process is essential for
      safe, effective and predicable facial rejuvenating surgery. The dentist generally
      has a long-lasting relationship with his patients and therefore may play an
      important role in advising patients with respect to the (im)possibilities of
      cosmetic facial surgery.

PMID- 24684135
TI  - [Loading and strength of single- and multi-unit fixed dental prostheses. 1.
      Retention and resistance].
AB  - The degree to which single- and multi-unit fixed dental prostheses are able to
      withstand loading forces is dependent, among other things, on the quality of
      their retention and resistance. The quality of the retention and resistance of
      the configuration of an abutment tooth prepared for a metal and metal-ceramic
      single-unit fixed dental prosthesis is determined by the configuration's
      convergence angle, the height, the volume, the interocclusal space, the cervical
      outline design, the additional preparations, the quality of the (build-up)
      restoration, and the surface roughness. A silicate ceramic single-unit fixed
      dental prosthesis is attached through adhesion using a composite cement, but the
      retention and resistance of an oxide ceramic single-unit fixed dental prosthesis
      is dependent on the abutment tooth configuration. Most types of multi-unit fixed
      dental prosthesis have the following additional retention and resistance
      determining factors: the position in the occlusal system, the number of abutment
      teeth and their mutual configurations, and the length of (cantilever) pontics. A
      resin-bonded fixed partial denture's retention and resistance are determined by
      its bonding as well as its enamel surface coverage and its resistance
      preparations.

PMID- 24684136
TI  - [Preprosthetic orthodontic treatments].
AB  - The objective of a preprosthetic orthodontic treatment is to position the teeth
      in such a way that a treatment with (fixed) dental prostheses is made possible or
      simplified or to affect the result of this treatment positively. Conceivable
      preprosthetic orthodontic treatments are: correcting primary orthodontic
      anomalies, closing or reducing interdental spaces and correcting the migration of
      teeth. In the case of unfavourable maxillomandibular relations, a preprosthetic
      surgical treatment is usually needed together with a preprosthetic orthodontic
      treatment. For children with agenesis and/or early loss of teeth and/or aberrant
      morphology of teeth, a treatment with fixed dental prostheses, either implant
      supported or not, may be indicated after the tooth development or in some cases
      earlier. Until that time, preprosthetic orthodontic treatments may be indicated
      to offer an aesthetically sound provisional solution and to achieve optimal teeth
      positions for the final fixed dental prostheses.

PMID- 24684137
TI  - Reply: To PMID 23671892.

PMID- 24684138
TI  - Sensitive electrochemical aptamer biosensor for dynamic cell surface N-glycan
      evaluation featuring multivalent recognition and signal amplification on a
      dendrimer-graphene electrode interface.
AB  - We demonstrate a multivalent recognition and highly selective aptamer signal
      amplification strategy for electrochemical cytosensing and dynamic cell surface N
      glycan expression evaluation by the combination of concanavalin A (Con A), a
      mannose binding protein, as a model, conjugated poly(amidoamine) dendrimer on a
      chemically reduced graphene oxide (rGO-DEN) interface, and aptamer- and
      horseradish peroxidase-modified gold nanoparticles (HRP-aptamer-AuNPs) as
      nanoprobes. In this strategy, the rGO-DEN can not only enhance the electron
      transfer ability but also provide a multivalent recognition interface for the
      conjugation of Con A that avoids the weak carbohydrate-protein interaction and
      dramatically improves the cell capture efficiency and the sensitivity of the
      biosensor for cell surface glycan. The high-affinity aptamer- and HRP-modified
      gold nanoparticles provide an ultrasensitive electrochemical probe with excellent
      specificity. As proof-of-concept, the detection of CCRF-CEM cell (human acute
      lymphoblastic leukemia) and its surface N-glycan was developed. It has
      demonstrated that the as-designed biosensor can be used for highly sensitive and
      selective cell detection and dynamic evaluation of cell surface N-glycan
      expression. A detection limit as low as 10 cells mL(-1) was obtained with
      excellent selectivity. Moreover, this strategy was also successfully applied for
      N-glycan expression inhibitor screening. These results imply that this biosensor
      has potential in clinical diagnostic and drug screening applications and endows a
      feasibility tool for insight into the N-glycan function in biological processes
      and related diseases. 

PMID- 24684139
TI  - S-nitrosylation analysis in Brassica juncea apoplast highlights the importance of
      nitric oxide in cold-stress signaling.
AB  - Reactive nitrogen species (RNS) including nitric oxide (NO) are important
      components of stress signaling. However, RNS-mediated signaling in the apoplast
      remains largely unknown. NO production measured in the shoot apoplast of Brassica
      juncea seedlings showed nonenzymatic nitrite reduction to NO. Thiol pool
      quantification showed cold-induced increase in the protein (including S
      nitrosothiols) as well as non protein thiols. Proteins from the apoplast were
      resolved as 109 spots on the 2-D gel, while S-nitrosoglutathione-treated (a NO
      donor), neutravidin-agarose affinity chromatography-purified S-nitrosylated
      proteins were resolved as 52 spots. Functional categorization after MALDI-TOF/TOF
      identification showed 41 and 38% targets to be metabolic/cell-wall-modifying and
      stress-related, respectively, suggesting the potential role(s) of S-nitrosylation
      in regulating these responses. Additionally, identification of cold-stress
      modulated putative S-nitrosylated proteins by nLC-MS/MS showed that only 38.4%
      targets with increased S-nitrosylation were secreted by classical pathway, while
      the majority (61.6%) of these were secreted by unknown/nonclassical pathways.
      Cold-stress-increased dehydroascorbate reductase and glutathione S-transferase
      activity via S-nitrosylation and promoted ROS detoxification by ascorbate
      regeneration and hydrogen peroxide detoxification. Taken together, cold-mediated
      NO production, thiol pool enrichment, and identification of the 48 putative S
      nitrosylated proteins, including 25 novel targets, provided the preview of RNS
      mediated cold-stress signaling in the apoplast. 

PMID- 24684140
TI  - Secondary glioblastoma multiform in a patient with CHARGE syndrome and prior
      radiation therapy for medulloblastoma.

PMID- 24684141
TI  - Directed energy transfer in films of CdSe quantum dots: beyond the point dipole
      approximation.
AB  - Understanding of Forster resonance energy transfer (FRET) in thin films composed
      of quantum dots (QDs) is of fundamental and technological significance in optimal
      design of QD based optoelectronic devices. The separation between QDs in the
      densely packed films is usually smaller than the size of QDs, so that the simple
      point-dipole approximation, widely used in the conventional approach, can no
      longer offer quantitative description of the FRET dynamics in such systems. Here,
      we report the investigations of the FRET dynamics in densely packed films
      composed of multisized CdSe QDs using ultrafast transient absorption spectroscopy
      and theoretical modeling. Pairwise interdot transfer time was determined in the
      range of 1.5 to 2 ns by spectral analyses which enable separation of the FRET
      contribution from intrinsic exciton decay. A rational model is suggested by
      taking into account the distribution of the electronic transition densities in
      the dots and using the film morphology revealed by AFM images. The FRET dynamics
      predicted by the model are in good quantitative agreement with experimental
      observations without adjustable parameters. Finally, we use our theoretical model
      to calculate dynamics of directed energy transfer in ordered multilayer QD films,
      which we also observe experimentally. The Monte Carlo simulations reveal that
      three ideal QD monolayers can provide exciton funneling efficiency above 80% from
      the most distant layer. Thereby, utilization of directed energy transfer can
      significantly improve light harvesting efficiency of QD devices. 

PMID- 24684142
TI  - Haematological complications of cystinosis.

PMID- 24684143
TI  - Impact of mood disorders on oral health-care utilization among middle-aged and
      older adults.
AB  - BACKGROUND: Good oral health improves quality of life and is an integral part of
      active aging. Similar to some other systemic diseases, mood disorders are more
      prevalent in middle to older ages and have an associated risk of developing poor
      oral health. Consequently, people with mood disorders need to have regular dental
      care. There is scarce evidence in Canada linking mood disorders to the use of
      professional oral care services. The purpose of this study was to investigate the
      association between mood disorders and utilization of oral health-care services
      in a population-based sample of middle aged and older adults in Canada. METHODS:
      Data were extracted from Canadian Community Health Survey - Healthy Aging, 2008.
      Multinomial logistic regression was used to investigate the association between
      mood disorders and oral care utilization, adjusted for the confounders. RESULTS:
      Among 30,354 respondents included in our sample, 2162 (6.9%) reported having mood
      disorders. After adjusting for age, sex, education, marital status, and dental
      insurance status, the respondents who had mood disorders had a significant
      increased odds of not visiting a dental professional in the past year (OR:1.21,
      95% CI: 1.08-1.35). The association of never visiting a dental professional and
      mood disorders was even stronger (OR: 1.49, 95% CI: 0.91-2.46). CONCLUSION: Mood
      disorders were found to have a strong association with underutilization of oral
      care services among aging adults of Canada. Given the associated poor oral health
      risks for elderly with mood disorders, oral health planners should strengthen the
      implementation of surveillance programs directed toward better oral health for
      this disadvantaged subpopulation.

PMID- 24684144
TI  - Getting granular: learning from the details of collaborative relationships.
AB  - Building a collaborative relationship with other professionals is both risky and
      full of opportunity. Stories of these relationships may reveal essential details
      that can help others succeed. They explain professional struggle and reward.
      Hypotheses that emerge, when tested, often lead to improved health care, cost
      savings, and a fulfilling work life. The authors share some of their own personal
      experiences in professional collaborative relationships as an invitation for
      readers to share theirs. In addition, new editors are introduced for the poetry;
      55-word-story; and Families, Systems, and Health in Our Lives sections of the
      journal.

PMID- 24684145
TI  - A tribute to Frank V. deGruy on the occasion of honoring him with the Donald
      Bloch Award.
AB  - Recognizes Frank V. deGruy as the recipient of the Donald Bloch Award. deGruy is
      a leader in integrated, collaborative primary care. He goes so far as to describe
      mental health and primary care as inseparable, saying attempts to segregate the
      two inevitably lead to inferior care. His accomplishments include the presidency
      of Collaborative Family Healthcare Association, during which he involved the
      organization in grant-getting, to study all aspects of the implementation of
      integration on the ground. In addition, he argued for and implemented
      collaboration with other like-minded organizations.

PMID- 24684146
TI  - Don Bloch award, 2013.
AB  - Frank deGruy, as recipient of the 2013 Don Bloch Award, presents a brief history
      of Bloch's contributions to the concept of collaboration in primary and mental
      health care. Bloch focused on the family as the unit of care for people with
      mental health problems, but saw something else: a person's psychological state
      was inextricably linked to his or her physical state. The health of one depended
      on the health of the other. Bloch started the journal that is now called
      Families, Systems, & Health, and then decided there was a need for an
      organization, which became the Collaborative Family Health care Association.

PMID- 24684147
TI  - Meta-Kucha: the margin or the mainstream?
AB  - The inexorable push in integrated care is to move collaboration between
      biomedical and psychosocial clinicians into the mainstream of health care. This
      effort requires expanding small models to scale, convening statewide
      transformation initiatives, and leaving the comfortable confines of safety net
      clinics to prove integration in the for-profit systems that dominate American
      health care. CFHA's (Collaborative Family Health care Association's) Pecha Kucha
      Plenary assembled compelling narratives from the fringes of our health care
      system. The competing calls from the mainstream and from the margins force
      tension into our dialogue. However, for our model to be widely embraced, we need
      blueprints that fit most patients in most clinics. What we learned from the Pecha
      Kucha narratives is that people at the margins find ways of asserting their
      voices and achieving their needs. Sometimes it is through their own resilience
      and disruptiveness; other times it is through an advocate from the mainstream who
      shares their stories in such a compelling way that they bypass our well-crafted
      models and spark our souls.

PMID- 24684148
TI  - Cold spotting.
AB  - Discusses issues that need to be addressed when collaborating to build a healthy
      community. One of these is the problem of "superutilizers." Superutilizers cost
      the health care system millions of dollars. Just a tiny fraction of patients
      account for greater than 50% of our health care costs. Urban blight is another.
      Health care is disintegrated in blighted neighborhoods. But urban blight is not
      the only place where health care is disintegrated. There are suburbs and gated
      communities where people live in isolation, lacking integrated primary care and
      behavioral health; poor collaboration between public health and medical
      providers, schools, and community organizations. A community of solution is a 50
      year-old term that may provide part of the solution. A community of solution
      finds the communities where health care problems are not just individuals; it
      identifies the problem and finds those who can provide a local solution. Our
      problems are not individual patients, but broader, systemic, community-based. The
      cure requires a community of solution linking public health, primary care, and
      behavioral health in explicit partnerships.

PMID- 24684149
TI  - Turning toward treating the seriously mentally ill in primary care.
AB  - Discusses the problem of people with serious mental illness not feeling welcome
      in primary care. The issue may be that health care providers are simply
      uncomfortable with the symptoms of serious mental illness, and this results in
      avoidance, both individually and as a system. This health disparity can only be
      addressed if the affected population is part of the conversation. Community-based
      primary care has a responsibility to address the physical health needs of the
      seriously mentally ill. To do this, we need to start by acknowledging our
      discomfort, listening deeply to the voices of people with severe mental illness,
      and learning how to intervene effectively to improve their health.

PMID- 24684150
TI  - Righting wrongs and reforming rights.
AB  - Discusses issues faced by LGBT people, such as a lack of equal civil rights and
      the need for extra legal and financial protection for families because partners
      cannot be married. The author notes that, in our society, it is no longer
      acceptable to be racist, but it is still okay to be homophobic. The many
      campaigns against gay marriage and efforts in the legislature to prevent change
      toward equal civil rights and protections are prime examples. In our current
      political climate, two things are very clear: (a) homophobia is freely tolerated
      and (b) the times are changing as we inch closer to equal rights every day. We
      are "righting wrongs and reforming rights."

PMID- 24684151
TI  - Clinician as patient: the gift of illness.
AB  - Most individuals have been touched by illness or have experienced illness
      themselves. This commentary illustrates how, as a clinician, my own life
      threatening illness has informed the way I work within integrated care and
      general health care practice.

PMID- 24684152
TI  - Health in hope: finding the soul of primary care.
AB  - Discusses the importance of offering hope to clients, no matter what their
      circumstances. Hope can be hard to find in situations of extreme poverty, and
      poverty breeds hopelessness. But hope promotes healthy behavior, like increased
      consumption of fruits and vegetables, regular exercise, safer sex, smoking
      cessation, and resumption of medications. That is the power of hope working in
      the heart of a patient to do what no clinician can: make good decisions, forgo
      bad habits, and see health as a priority and reality in life. Foster hope. Hope
      is healthy.

PMID- 24684153
TI  - Examining the utility of behavioral health integration in well-child visits:
      implications for rural settings.
AB  - The purpose of this study was to assess the effect of integrating behavioral
      health services into well-child visits in underserved, remote, and/or fringe
      areas. Specifically, the following were examined: the structure of the well-child
      visit for standard care in comparison to when a behavioral health provider was
      integrated into the visit and the effect of integrating a behavioral health
      provider on behavioral health topics covered and parent satisfaction.
      Participants were 94 caregivers of children attending well-child visits. Group
      differences were examined for participants in well-child visits with a behavioral
      health provider and participants in a standard well-child visit. Findings suggest
      a statistically significant increase in caregiver-rated perception for the number
      of topics covered with the integration of a behavioral health provider in the
      well-child visits. No significant effects of caregiver-rated helpfulness or
      satisfaction were observed. Implications for the findings and future research
      directions are discussed.

PMID- 24684155
TI  - Integrated primary care: a systematic review of program characteristics.
AB  - The integration of behavioral health services into primary care medical settings
      may be part of the solution to the fragmented health care system currently found
      in the United States. Although integrated primary care (IPC) is implemented in
      various locations across the United States, little information is available about
      how IPC is specifically practiced. Using a systematic review design, we extracted
      data from 76 articles to examine 6 categories of IPC program characteristics,
      including collaboration practices (e.g., shared decision-making, written
      communication, hallway conversations), program models, behavioral health
      interventions, behavioral health training and supervision, behavioral health
      provider type, and setting. Findings show that most IPC programs include
      psychoeducation, medication, follow-up contact, psychotherapy, and at least 1
      care management strategy as part of treatment. Fewer than half of researchers
      report communication between providers, and even fewer report collaboration as a
      "shared decision making process." A third of researchers report training and/or
      supervising behavioral health providers to work in an IPC program, and a fourth
      report recruiting nurses as behavioral health providers. Of all the studies,
      family-based interventions were used in 1. We recommend that future researchers
      report more information about collaboration processes as well as training and
      supervision of behavioral health providers. We also recommend that researchers
      develop IPC programs that involve family members in treatment and better
      implement theory into future IPC programs to support conceptualization and
      replication of IPC program models.

PMID- 24684156
TI  - Adapting acceptance and commitment therapy for parents of children with life
      threatening illness: pilot study.
AB  - We piloted a novel parent-targeted intervention, Take A Breath (TAB), for parents
      of children diagnosed with a life-threatening illness (LTI) with the aim of
      reducing parental distress. Parents were assisted to adapt to their child's
      diagnosis, treatment, and recovery via TAB's combined acceptance and commitment
      therapy (ACT) and problem-solving skills training (PSST) approach. Participants
      were 11 parents of children with a diagnosis of cancer, or who had life-saving
      cardiac surgery at least 4 months prior. Parents completed questionnaires at pre,
      post, and 6-month follow-up assessing parent posttraumatic stress symptoms
      (PTSS), the emotional impact of the child's LTI (e.g., feelings of uncertainty,
      guilt and sorrow, emotional resources), and psychological elements targeted by
      the intervention (parental psychological flexibility and mindfulness). Parents
      reported significant reductions in PTSS and emotional impact from their child's
      LTI, along with significant improvements in parental psychological flexibility
      and mindfulness. Effect sizes were medium to large, and improvements were
      maintained at 6-month follow-up. Our pilot indicates the TAB intervention has
      promise for preventing or reducing parental distress associated with child LTI
      and warrants more rigorous evaluation. Although preliminary, these findings
      suggest that targeting parents' subjective perceptions of their child's LTI may
      be an effective approach to reducing parental distress. Our results also indicate
      the potential for such an approach to be adopted across diverse child diagnoses
      in the acute pediatric setting. Further, our findings provide early indications
      that ACT combined with PSST is an appropriate therapeutic approach within this
      context.

PMID- 24684159
TI  - Getting beyond "pandora-phobia".
AB  - Clinicians, regardless of discipline, tend to prefer those areas of their
      practice in which they feel a sense of mastery, a confidence in their ability to
      manage the conditions being presented to them by their patients. In contrast, in
      clinical scenarios when the history and/or physical exam findings consist of
      vague and difficult-to-interpret elements, the resulting discordance may
      challenge some clinicians' sense of mastery. This common primary care scenario,
      the presentation of symptoms for which no "organic," pathologic, physical
      diagnosis can be discerned, is referred to as Medically Unexplained Symptoms.
      Clinical trainees experience "complicated" patients as particularly challenging,
      and may hesitate to ask about the patients' thoughts and feelings, resulting from
      a fear of getting entangled in a conversation from which the trainee cannot
      easily escape. The author refers to this as "Pandora-phobia," from Pandora in
      Greek mythology and the fear of opening Pandora's box. The task in the training
      environment is to help young clinicians gain experience in "lifting the lid" of
      Pandora's box. This is ideally achieved by trainees observing the role-modeling
      of accomplished mentors, and their working with capable, multidisciplinary
      teammates. This is the beauty of the collaborative, integrated care delivery
      team; there is a balanced set of skills and expertise brought by an expanded
      number of caring persons supporting those patients whose conditions most need a
      combination of biomedical and psychosocial expertise.

PMID- 24684161
TI  - Dietary exposure and health risk assessment for 14 toxic and essential trace
      elements in Yaounde: the Cameroonian total diet study.
AB  - Dietary exposure to trace elements (aluminium, antimony, barium, cadmium, lead,
      nickel, vanadium, copper, manganese, molybdenum, germanium, lithium, strontium
      and tellurium) was assessed by the total diet study (TDS) method. Sixty-four
      pooled samples representing 96.5% of the diet in Yaounde, Cameroon, were prepared
      "as consumed" before analysis. Consumption data were sourced from a households'
      budget survey. Dietary exposures were compared with health-based guidance or
      nutritional values and to worldwide TDS results. The health-based guidance value
      was exceeded by <= 0.2% of the study population for aluminium, antimony, barium,
      cadmium, nickel and vanadium. For lead, the observed 95th percentile of exposure
      (3.05 ug kg(-1) body weight day(-1)) equals the critical value considered by
      JECFA for cardiovascular effects; therefore, risk to health cannot be excluded
      for certain consumer groups. The population at risk of excess intake for
      manganese, copper, molybdenum and nickel was considered to be low (<= 0.3%). The
      prevalence of inadequate intake was estimated at 5.9% for copper and was nil for
      molybdenum. Due to the lack of toxicological and/or nutritional consistent data
      to perform a risk assessment, dietary exposures to germanium, lithium, strontium
      and tellurium were provided as supplementary data. The food groups highest
      contributors to exposure were "tubers and starches" for aluminium (27%), lead
      (39%) and copper (26%), "cereals and cereal products" for cadmium (54%) and
      manganese (35%), "fruits, vegetables and oilseeds" for barium (34%), molybdenum
      (49%) and nickel (31%), "beverages" for antimony (27%) and "fish" for vanadium
      (43% - lower bound). Measures should be recommended to maintain low levels of
      exposure before the problem could become an important health or trade issue.

PMID- 24684160
TI  - Administration of exogenous acylated ghrelin or rikkunshito, an endogenous
      ghrelin enhancer, improves the decrease in postprandial gastric motility in an
      acute restraint stress mouse model.
AB  - BACKGROUND: Physical or psychological stress causes functional disorders in the
      upper gastrointestinal tract. This study aims to elucidate the ameliorating
      effect of exogenous acylated ghrelin or rikkunshito, a Kampo medicine which acts
      as a ghrelin enhancer, on gastric dysfunction during acute restraint stress in
      mice. METHODS: Fasted and postprandial motor function of the gastric antrum was
      wirelessly measured using a strain gauge force transducer and solid gastric
      emptying was detected in mice exposed to restraint stress. Plasma corticosterone
      and ghrelin levels were also measured. To clarify the role of ghrelin on
      gastrointestinal dysfunction in mice exposed to stress, exogenous acylated
      ghrelin or rikkunshito was administered, then the mice were subjected to
      restraint stress. KEY RESULTS: Mice exposed to restraint stress for 60 min
      exhibited delayed gastric emptying and increased plasma corticosterone levels.
      Gastric motility was decreased in mice exposed to restraint stress in both
      fasting and postprandial states. Restraint stress did not cause any change in
      plasma acylated ghrelin levels, but it significantly increased the plasma des
      acyl ghrelin levels. Administration of acylated ghrelin or rikkunshito improved
      the restraint stress-induced delayed gastric emptying and decreased antral
      motility. Ameliorating effects of rikkunshito on stress-induced gastric
      dysfunction were abolished by simultaneous administration of a ghrelin receptor
      antagonist. CONCLUSIONS & INFERENCES: Plasma acylated/des-acyl ghrelin imbalance
      was observed in acute restraint stress. Supplementation of exogenous acylated
      ghrelin or enhancement of endogenous ghrelin signaling may be useful in the
      treatment of decreased gastric function caused by stress.

PMID- 24684162
TI  - Partial clinical response to anakinra in severe palmoplantar pustular psoriasis.
AB  - BACKGROUND: Palmoplantar pustular psoriasis is a clinical psoriasis variant
      characterised by a high impact on quality of life and poor response to biologics
      approved for plaque type psoriasis.The recombinant interleukin-1 (IL-1) receptor
      antagonist anakinra has been recently used for the treatment of isolated
      refractory cases of generalised pustular psoriasis with contrasted results.
      OBJECTIVES: To report the clinical response in two patients treated with anakinra
      as salvage therapy in two patients with severe palmoplantar pustular psoriasis
      refractory to currently available antipsoriatic systemic therapies. METHODS:
      Anakinra was given subcutaneously at the daily dose of 100 mg, and clinical
      response was evaluated using the palmoplantar psoriasis area and severity index
      (PPPASI). RESULTS: Only partial and transient responses were observed in both
      patients, who had to stop anakinra due to lack of efficacy and to side effects.
      CONCLUSION: Anakinra appears to provide only partial clinical improvement in
      refractory palmoplantar pustular psoriasis. Prospective clinical studies on
      larger populations are warranted to investigate more accurately both efficacy and
      safety of IL-1-inhibiting strategies in pustular psoriasis.

PMID- 24684163
TI  - Phlebitis risk varies by peripheral venous catheter site and increases after 96
      hours: a large multi-centre prospective study.
AB  - AIMS: This multi-centre prospective field study evaluated whether peripheral
      venous catheter site of insertion influences the risk of catheter-related
      phlebitis. Potential predictors of phlebitis were also investigated. BACKGROUND:
      Millions of patients worldwide use peripheral venous catheters, which frequently
      cause local complications including phlebitis, infection and obstruction.
      Although phlebitis predictors have been broadly investigated, uncertainties
      remain on the potential effect of cannulation anatomical site, duration and the
      appropriate time for catheter removal. DESIGN: A prospective cohort design was
      carried out from January-June 2012. METHODS: The clinical course of each patient
      who received a new peripheral venous catheter for any cause in five Italian
      hospitals was followed by trained nurses until catheter removal. The presence of
      phlebitis was assessed every 24 hours using the Visual Infusion Phlebitis score.
      Analyses were based upon multilevel mixed-effects regression. RESULTS: The final
      sample consisted of 1498 patients. The average time for catheters in situ was
      65.6 hours and 23.6% of the catheters were in place beyond 96 hours. Overall
      phlebitis incidence was 15.4%, 94.4% of which were grade 1. The likelihood of
      phlebitis independently increased with increasing catheter duration, being
      highest after 96 hours. Compared with patients with catheter placed in the dorsum
      of the hand (22.8% of the sample), those with the catheter located in the
      antecubital fossa (34.1%) or forearm were less likely to have a phlebitis of any
      grade. CONCLUSIONS: Antecubital fossa and forearm veins may be preferential sites
      for peripheral venous cannulation. Our results support Centers for Disease
      Control and Prevention recommendations to replace catheters in adults no later
      than 96 hours. A relevant proportion of healthcare personnel did not adhere to
      such guidelines - more attention to this issue is required.

PMID- 24684164
TI  - Proteomic analysis of adipose tissue: informing diabetes research.
AB  - Diabetes, one of the most common endocrine diseases worldwide, results from
      complex pathophysiological mechanisms that are not fully understood. Adipose
      tissue is considered a major endocrine organ and plays a central role in the
      development of diabetes. The identification of the adipose tissue-derived factors
      that contribute to the onset and progression of diabetes will hopefully lead to
      the development of preventive and therapeutic interventions. Proteomic techniques
      may be useful tools for this purpose. In the present review, we have summarized
      the studies conducting adipose tissue proteomics in subjects with diabetes and
      insulin resistance, and discussed the proteins identified in these studies as
      candidates to exert important roles in these disorders. 

PMID- 24684165
TI  - Triple combination as adjuvant to cryotherapy in the treatment of solar
      lentigines: investigator-blinded, randomized clinical trial.
AB  - BACKGROUND: Post-inflammatory hyperpigmentation is a frequent concern when
      treating solar lentigines. OBJECTIVES: To assess the safety and efficacy of a
      triple combination cream with fluocinolone acetonide 0.01%, hydroquinone 4% and
      tretinoin 0.05% as adjuvant to cryotherapy in the treatment of solar lentigines
      in hands dorsum, and in the prevention of post-inflammatory hyperpigmentation
      after cryotherapy. METHODS: This prospective, randomized, controlled,
      investigator-blinded, single-centre study enrolled 50 patients. Twenty-five
      patients received a 2-week daily triple combination cream plus sunscreen pre
      treatment and 25 received sunscreen alone. After that, cryotherapy was performed
      in all patients followed by a 3-week recovery period. After this period, patients
      received the same initial treatment and were followed up for 8 weeks. Melanin and
      erythema levels of a target and a control lentigo were objectively measured using
      a narrowband reflectance spectrophotometer. Lentigines count, colour homogeneity
      and global improvement were also assessed. RESULTS: The number of solar
      lentigines reduced in the first 2 weeks only in patients who used the triple
      combination 25 +/- 7 vs. 22 +/- 8 (P < 0.0001), and reduced at the end of the
      study for both groups (P < 0.0001). The melanin levels also reduced in the first
      2 weeks only in patients who used the triple combination 297 +/- 69 vs. 273 +/-
      66 (P < 0.0001) and reduced at the end of the study for both groups (P < 0.0001).
      Erythema and residual blisters from cryotherapy were the reported adverse
      reactions. CONCLUSION: Triple combination cream can be used to enhance the
      resolution of solar lentigines, and to significantly reduce melanin levels and
      lentigines count, improving treatment results. It was well-tolerated and did not
      increase the occurrence of neither erythema nor other side-effects after the
      cryotherapy.

PMID- 24684166
TI  - Nanopore-based instruments as biosensors for future planetary missions.
AB  - Data from automated orbiters and landers have dashed humankind's hopes of finding
      complex life-forms elsewhere in the Solar System. The focus of exobiological
      research was thus forced to shift from the detection of life through simple
      visual imaging to complex biochemical experiments aimed at the detection of
      microbial activity. Searching for biosignatures over interplanetary distances is
      a formidable task and poses the dilemma of what are the proper experiments that
      can be performed on-site to maximize the chances of success if extraterrestrial
      life is present but not evident. Despite their astonishing morphological
      diversity, all known organisms on Earth share the same basic molecular
      architecture; thus the vast majority of our detection and identification
      techniques are b(i)ased on Terran biochemistry. There is, however, a distinct
      possibility that life may have emerged elsewhere by using other molecular
      building blocks, a fact that is likely to make the outcome of most of the current
      molecular biological and biochemical life-detection protocols difficult to
      interpret if not completely ineffective. Nanopore-based sensing devices allow the
      analysis of single molecules, including the sequence of informational biopolymers
      such as DNA or RNA, by measuring current changes across an electrically resistant
      membrane when the analyte flows through an embedded transmembrane protein or a
      solid-state nanopore. Under certain basic assumptions about their physical
      properties, this technology has the potential to discriminate and possibly
      analyze biopolymers, in particular genetic information carriers, without prior
      detailed knowledge of their fundamental chemistry and is sufficiently portable to
      be used for automated analysis in planetary exploration, all of which makes it
      the ideal candidate for the search for life signatures in remote watery
      environments such as Mars, Europa, or Enceladus.

PMID- 24684167
TI  - Knockdown of the Arabidopsis thaliana chloroplast protein disulfide isomerase 6
      results in reduced levels of photoinhibition and increased D1 synthesis in high
      light.
AB  - A chloroplast protein disulfide isomerase (PDI) was previously proposed to
      regulate translation of the unicellular green alga Chlamydomonas reinhardtii
      chloroplast psbA mRNA, encoding the D1 protein, in response to light. Here we
      show that AtPDI6, one of 13 Arabidopsis thaliana PDI genes, also plays a role in
      the chloroplast. We found that AtPDI6 is targeted and localized to the
      chloroplast. Interestingly, AtPDI6 knockdown plants displayed higher resistance
      to photoinhibition than wild-type plants when exposed to a tenfold increase in
      light intensity. The AtPDI6 knockdown plants also displayed a higher rate of D1
      synthesis under a similar light intensity. The increased resistance to
      photoinhibition may not be rationalized by changes in antenna or non
      photochemical quenching. Thus, the increased D1 synthesis rate, which may result
      in a larger proportion of active D1 under light stress, may led to the decrease
      in photoinhibition. These results suggest that, although the D1 synthesis rates
      observed in wild-type plants under high light intensities are elevated, repair
      can potentially occur faster. The findings implicate AtPDI6 as an attenuator of
      D1 synthesis, modulating photoinhibition in a light-regulated manner. 

PMID- 24684168
TI  - The TOR signaling pathway regulates vegetative development and virulence in
      Fusarium graminearum.
AB  - The target of rapamycin (TOR) signaling pathway plays critical roles in
      controlling cell growth in a variety of eukaryotes. However, the contribution of
      this pathway in regulating virulence of plant pathogenic fungi is unknown. We
      identified and characterized nine genes encoding components of the TOR pathway in
      Fusarium graminearum. Biological, genetic and biochemical functions of each
      component were investigated. The FgFkbp12-rapamycin complex binds to the FgTor
      kinase. The type 2A phosphatases FgPp2A, FgSit4 and FgPpg1 were found to interact
      with FgTap42, a downstream component of FgTor. Among these, we determined that
      FgPp2A is likely to be essential for F. graminearum survival, and FgSit4 and
      FgPpg1 play important roles in cell wall integrity by positively regulating the
      phosphorylation of FgMgv1, a key MAP kinase in the cell wall integrity pathway.
      In addition, the FgPpg1 interacting protein, FgTip41, is involved in regulating
      mycelial growth and virulence. Notably, FgTip41 does not interact with FgTap42
      but with FgPpg1, suggesting the existence of FgTap42:FgPpg1:FgTip41 heterotrimer
      in F. graminearum, a complex not observed in the yeast model. Collectively, we
      defined a genetic regulatory framework that elucidates how the TOR pathway
      regulates virulence and vegetative development in F. graminearum. 

PMID- 24684169
TI  - Lipase inhibitory activity of chlorophyll a, isofucosterol and saringosterol
      isolated from chloroform fraction of Sargassum thunbergii.
AB  - Three compounds (chlorophyll a, isofucosterol and saringosterol) were isolated
      from chloroform fraction of Sargassum thunbergii extract. The three compounds had
      two- to fourfold lower lipase inhibitory activity than that of the CHCl3:MeOH
      (C:M) (100:1) fraction (fraction I, 83.78% at 1 mg/mL). These results suggested
      that the high lipase inhibitory activity of fraction I was attributable to the
      actions of the three compounds. Therefore, S. thunbergii has potential for
      application as an anti-obesity agent.

PMID- 24684170
TI  - An analysis of transplant glomerulopathy and thrombotic microangiopathy in kidney
      transplant biopsies.
AB  - Glomerular diseases of the transplanted kidney are the most important cause of
      poor long- term outcome. The estimation of the magnitude of this problem and an
      elucidation of pathogenic mechanism is essential for improvement of graft
      survival. This study from the Indian subcontinent aims (i) to determine the
      incidence of transplant glomerulopathy (TG) and thrombotic microangiopathy (TMA)
      in a large cohort of indicated renal transplant biopsies, (ii) to evaluate the
      histological and ultrastructural features of TG and TMA, and (iii) to assess the
      relationship between the two glomerular lesions. Of a total of 1792 indication
      renal transplant biopsies received over 5 years (2006-2010), 266 biopsies (of 249
      patients) had significant glomerular pathology and were further analyzed along
      with immunofluorescence, electron microscopy (EM), and C4d immunohistochemistry.
      TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08%
      of allograft biopsies, respectively, which constitutes 40.23% and 34.2% of
      biopsies with significant glomerular lesions. Pathologic antibody-mediated
      rejection (AMR) is associated with both TG and TMA in 71% and 46.5%,
      respectively. A coexistent TG was found in 18.4% of biopsies with TMA.
      Endothelial swelling with subendothelial widening, a feature of TMA, is also seen
      in early TG by EM. Our findings support the concept that TG evolves from a
      smoldering TMA of various causes. 

PMID- 24684171
TI  - Neuromonitoring with pulse-train stimulation for implantation of thoracic pedicle
      screws: a blinded and randomized clinical study. Part 1. Methods and alarm
      criteria.
AB  - OBJECT: Reports of the accuracy of existing neuromonitoring methods for detecting
      or preventing medial malpositioning of thoracic pedicle screws have varied widely
      in their claimed effectiveness. The object of this study was to develop, test,
      and validate a novel neuromonitoring method for preventing medial malpositioning
      of pedicle screws in the thoracic spine during surgery. METHODS: This is a
      prospective, blinded and randomized study using a novel combination of input (4
      pulse stimulus trains delivered within the pedicle track) and output (evoked
      electromyography from leg muscles) to detect pedicle track trajectories that-once
      implanted with a screw-would cause that screw to breach the pedicle's medial wall
      and encroach upon the spinal canal. For comparison, the authors also used screw
      stimulation as an input and evoked electromyogram from intercostal and abdominal
      muscles as output measures. Intraoperative electrophysiological findings were
      compared with postoperative CT scans by multiple reviewers blinded to patient
      identity or intraoperative findings. RESULTS: Data were collected from 71
      patients, in whom 802 screws were implanted between the T-1 and L-1 vertebral
      levels. A total of 32 screws ended up with screw threads encroaching on the
      spinal canal by at least 2 mm. Pulse-train stimulation within the pedicle track
      using a ball-tipped probe and electromyography from lower limb muscles correctly
      predicted all 32 (100%) of these medially malpositioned screws. The combination
      of pedicle track stimulation and electromyogram response from leg muscles proved
      to be far more effective in predicting these medially malpositioned screws than
      was direct screw stimulation and any of the target muscles (intercostal,
      abdominal, or lower limb muscles) we monitored. Based on receiver operating
      characteristic analysis, the combination of 10-mA (lower alarm) and 15-mA
      stimulation intensities proved most effective for detection of pedicle tracks
      that ultimately gave rise to medially malpositioned screws. Additional results
      pertaining to the impact of feedback of these test results on surgical decision
      making are provided in the companion report. CONCLUSIONS: This novel
      neuromonitoring approach accurately predicts medially malpositioned thoracic
      screws. The approach could be readily implemented within any surgical program
      that is already using contemporary neuromonitoring methods that include
      transcranial stimulation for monitoring motor evoked potentials.

PMID- 24684173
TI  - Gliptins - do they increase cardiovascular risk or benefit?
AB  - INTRODUCTION: In 2008, the US FDA required all new glucose-lowering therapies to
      show cardiovascular safety, and this applies to the dipeptidyl peptidase-4
      inhibitors ('gliptins'). AREAS COVERED: The cardiovascular safety trials of
      saxagliptin and alogliptin have recently been published and are the subject of
      this evaluation. EXPERT OPINION: The Saxagliptin Assessment of Vascular Outcomes
      Recorded in Patients with Diabetes Mellitus - Thrombolysis in Myocardial
      Infarction 53 trial and Examination of Cardiovascular Outcomes with Alogliptin
      versus Standard of Care were both multicentre, randomised, double-blind, placebo
      controlled, Phase IV clinical trials. These trials showed that saxagliptin and
      alogliptin did not increase the primary end point, which was a composite of
      cardiovascular outcomes that did not include hospitalisations for heart failure.
      However, saxagliptin significantly increased hospitalisation for heart failure,
      which was a component of the secondary end point. The effect of alogliptin on
      hospitalisations for heart failure has not been reported. Neither agent improved
      cardiovascular outcomes. As there is no published evidence of improved outcomes
      with gliptins, it is unclear to us why these agents are so widely available for
      use. We suggest that the use of gliptins be restricted to Phase IV clinical
      trials until such time as cardiovascular safety and benefits/superiority are
      clearly established.

PMID- 24684174
TI  - Report on a NASA astrobiology institute-funded workshop without walls: stellar
      stoichiometry.
AB  - We report on the NASA Astrobiology Institute-funded Workshop Without Walls
      entitled "Stellar Stoichiometry," hosted by the "Follow the Elements" team at
      Arizona State University in April 2013. We describe several innovative practices
      we adopted that made effective use of the Workshop Without Walls
      videoconferencing format, including use of information technologies, assignment
      of scientific tasks before the workshop, and placement of graduate students in
      positions of authority. A companion article will describe the scientific results
      arising from the workshop. Our intention here is to suggest best practices for
      future Workshops Without Walls.

PMID- 24684175
TI  - New monoterpenoid alkaloids from the aerial parts of Uncaria hirsuta.
AB  - To investigate the chemical constituents of medicinal plant Uncaria hirsuta,
      three new monoterpenoid alkaloids, named hirsutanines A-C (1-3), were isolated.
      Their structures with absolute configurations were elucidated by means of NMR, X
      ray diffraction and CD analysis. Compound 3 was the first dimeric monoterpenoid
      alkaloid obtained from genus Uncaria. 

PMID- 24684176
TI  - Neuromonitoring with pulse-train stimulation for implantation of thoracic pedicle
      screws: a blinded and randomized clinical study. Part 2. The role of feedback.
AB  - OBJECT: The authors have reported in Part 1 of this study on a novel
      neuromonitoring test for the prevention of medial malpositioning of thoracic
      pedicle screws. In the present paper they examine the impact of providing the
      results of the test as intraoperative feedback to the surgical team. METHODS:
      This is the second part of a 2-part report of a prospective, blinded and
      randomized neuromonitoring study designed to lower the incidence of medially
      malpositioned thoracic pedicle screws. Details of the neuromonitoring technique
      and data supporting the alarm criteria used are contained in the companion
      article (Part 1). For the majority of pedicle screw placements, intraoperative
      test results were withheld from the study team (that is, the team members were
      blinded to the test results). However, for a limited number of pedicle sites the
      authors provided one of 2 forms of testing feedback to the surgical team: 1)
      "break the blind" feedback, if testing suggested that screw placement would
      result in direct contact between screw and the dura mater; and 2) "planned"
      feedback, beginning during the later stages of the study and provided for 50% of
      pedicle sites. Feedback gave the surgeon the opportunity to adjust the trajectory
      that the screw would ultimately take within the pedicle. The final screw position
      relative to the pedicle's medial wall for all sites in which feedback was
      withheld from the surgical team was compared with the screw position for those
      sites in which either form of feedback ("break the blind" or "planned") was
      provided to and acted upon by the surgical team. RESULTS: Of the 820 pedicle
      tracks tested among the 71 surgical cases included in this study, a total of 684
      were operated upon without any form of feedback. Planned feedback was provided
      for an additional 107 pedicle tracks, of which 15 triggered an intraoperative
      alarm (evoked electromyogram response in leg muscles to stimulus intensity <= 10
      mA) leading to a warning to the surgical team of a medially biased pedicle track.
      Finally, the blind was broken 29 times, in each case when testing revealed a
      particularly low threshold (<= 4 mA) for evoked responses in leg muscles when
      stimulating along the pedicle track with the ball-tipped probe. As detailed in
      the companion paper to this one, there were 32 screws with threads lying at least
      2 mm medial to the pedicle wall. In all 32 instances (100%), either these screws
      were in the "no feedback" category (n = 29) or they were in a feedback category
      but the surgeon elected to not revise the pedicle-track trajectory. Two patients
      returned to the operating room for revision of screw placements because the
      screws were encroaching upon the central canal; the pedicle tracks for these
      screws had been in the "no feedback" category. CONCLUSIONS: This is the first
      blinded and randomized study to prove that implementing a novel neuromonitoring
      strategy during placement of thoracic pedicle screws can significantly reduce the
      incidence of clinically relevant thoracic pedicle screw medial malpositioning.

PMID- 24684178
TI  - Circulating T-regulatory cells in neuroblastoma: a pilot prospective study.
AB  - The objective of our study was to determine baseline Tregs in neuroblastoma
      patients and correlate with patient characteristics, their change with therapy
      and at relapse/progression. Flow-cytometric analysis for Treg cells
      [CD4+CD25+FoxP3+] was done in 14 de novo neuroblastoma patients at diagnosis,
      post-neoadjuvant chemotherapy and at relapse/progression, along with six healthy
      controls. Patients had significantly higher baseline Treg frequency than controls
      [Mean 9.84 +/- 3.84 vs 3.16 +/- 1.49, P < .001]; higher mean Treg frequency in
      patients with tumors >10 cm (P = .004) and there was significant reduction in
      Treg frequency with neoadjuvant chemotherapy when compared with the baseline
      value [Mean 3.07 +/- 1.24 vs 9.72 +/- 3.84, P = .007]. 

PMID- 24684177
TI  - Luteal expression of thyroid hormone receptors during gestation and postpartum in
      the rat.
AB  - BACKGROUND: Progesterone (P4) is the main steroid secreted by the corpora lutea
      (CL) and is required for successful implantation and maintenance of pregnancy.
      Although adequate circulating levels of thyroid hormone (TH) are needed to
      support formation and maintenance of CL during pregnancy, TH signaling had not
      been described in this gland. We determined luteal thyroid hormone receptor
      isoforms (TR) expression and regulation throughout pregnancy and under the
      influence of thyroid status, and in vitro effects of triiodothyronine (T3)
      exposure on luteal P4 synthesis. METHODS: Euthyroid female Wistar rats were
      sacrificed by decapitation on gestational day (G) 5, G10, G15, G19, or G21 of
      pregnancy or on day 2 postpartum (L2). Hyperthyroidism and hypothyroidism were
      induced in female Wistar rats by daily administration of thyroxine (T4; 0.25
      mg/kg subcutaneously) or 6-propyl-2-thiouracil (PTU; 0.1 g/L in drinking water),
      respectively. Luteal TR expression of mRNA was determined using real-time reverse
      transcription quantitative polymerase chain reaction, and of protein using
      Western blot and immunohistochemistry. Primary cultures of luteal cells and of
      luteinized granulosa cells were used to study in vitro effects of T3 on P4
      synthesis. In addition, the effect of T3 on P4 synthesis under basal conditions
      and under stimulation with luteinizing hormone (LH), prolactin (PRL), and
      prostaglandin E2 (PGE2) was evaluated. RESULTS: TRalpha1, TRalpha2, and TRbeta1
      mRNA were present in CL, increasing during the first half and decreasing during
      the second half of pregnancy. At the protein level, TRbeta1 was abundantly
      expressed during gestation reaching a peak at G19 and decreasing afterwards.
      TRalpha1 was barely expressed during early gestation, peaked at G19, and
      diminished thereafter. Expression of TRbeta1 and TRalpha1 at the protein and mRNA
      level were not influenced by thyroid status. T3 neither modified P4 secretion
      from CL of pregnancy nor its synthesis in luteinized granulosa cells in culture.
      CONCLUSIONS: This study confirms for the first time the presence of TR isoforms
      in the CL during pregnancy and postpartum, identifying this gland as a TH target
      during gestation. TR expression is modulated in this tissue in accordance with
      the regulation of P4 metabolism, and the abrupt peripartum changes suggest a role
      of TH during luteolysis. However, TH actions on the CL do not seem to be related
      to a direct regulation of P4 synthesis.

PMID- 24684179
TI  - Divide and conquer: subproteomic approaches toward gastric cancer biomarker and
      drug target discovery.
AB  - The discovery of biomarkers for early detection and treatment for gastric cancer
      are two important gaps that proteomics have the potential to fill. Advancements
      in mass spectrometry, sample preparation and separation strategies are crucial to
      proteomics-based discoveries and subsequent translations from bench to bedside. A
      great number of studies exploiting various subproteomic approaches have emerged
      for higher-resolution analysis (compared with shotgun proteomics) that permit
      interrogation of different post-translational and subcellular compartmentalized
      forms of the same proteins as determinants of disease phenotypes. This is a
      unique and key strength of proteomics over genomics. In this review, the salient
      features, competitive edges and pitfalls of various subproteomic approaches are
      discussed. We also highlight valuable insights from several subproteomic studies
      that have increased our understanding of the molecular etiology of gastric cancer
      and the findings that led to the discovery of potential biomarkers/drug targets
      that were otherwise not revealed by conventional shotgun expression proteomics. 

PMID- 24684180
TI  - Predictors of attendance in a group-based model of case management for supported
      housing.
AB  - OBJECTIVE: To examine the frequency and predictors of group attendance in a new
      group-intensive peer support (GIPS) model of case management for the Veterans
      Affairs supported housing program. METHODS: Administrative data and group
      attendance records from 1 GIPS program were analyzed using bivariate and
      regression analyses. RESULTS: Of 295 clients, 42% attended at least 1 group and
      attended an average of 3 groups per month. There were no significant differences
      in any demographic, psychosocial, or clinical characteristics at baseline between
      group attenders and nongroup attenders. However, among group attenders, those who
      entered the program with more days homeless in the past month and more mental
      health symptoms attended groups more frequently. CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: These results provide support for group-based models of care in
      supported housing and suggest those with more extensive housing and mental health
      problems may be more receptive to attending groups.

PMID- 24684181
TI  - For parents with mental health conditions: the chance to "have it all" at work
      and at home.
AB  - TOPIC: Evidence-based Individual Placement and Support (IPS) supported employment
      provides opportunities to individualize supports for parents with mental health
      conditions who are vulnerable to financial insecurity and family instability.
      PURPOSE: Adults living with serious mental health conditions may have goals
      related to both work and parenting. IPS employment specialists can capitalize on
      our understanding of the challenges faced by parents living with serious mental
      health conditions to improve the economic wellbeing of these individuals and
      their families. SOURCES USED: Data include a summary of analyses of the U.S.
      National Survey on Drug Use and Health as well as first-person accounts from
      parents and employment specialists. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      Empirical and anecdotal evidence support the relevance of discussing goals for
      parenting and family life with adults living with mental health conditions in the
      context of job assessment, placement, and support to promote goal achievement in
      both role domains-employment and parenting.

PMID- 24684182
TI  - Implementation of evidence-based supported employment in regional Australia.
AB  - OBJECTIVE: To implement the Individual Placement and Support (IPS) approach at 4
      locations in regional New South Wales, Australia. Outcomes attained were compared
      with a national non-IPS program and with international trials of IPS within and
      outside the United States. METHODS: Four IPS programs were established through
      formal partnerships between mental health services and disability employment
      services. Ninety-five mental health service clients commenced employment
      assistance and were tracked for a minimum of 12 months. RESULTS: Two sites
      achieved good fidelity to IPS principles, and 2 sites achieved fair fidelity. IPS
      clients had 3.5 times greater odds of attaining 13 weeks' employment than those
      receiving assistance in the national network of disability employment services.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Implementing IPS is challenging in the
      Australian service delivery context. Factors other than program fidelity appear
      to contribute to excellent employment outcomes. Further research is needed to
      identify these factors.

PMID- 24684183
TI  - Availability of services for parents living with mental disorders: a province
      wide survey.
AB  - OBJECTIVE: There is evidence that parents living with mental disorders have
      limited access to parenting support. We conducted a survey of mental health
      agencies in Ontario, Canada, to establish a benchmark from which progress in
      service availability can be evaluated, and to identify any barriers to
      availability in terms of program location and parent gender. METHOD: We surveyed
      119 directors of community and inpatient mental health service agencies (54%
      response rate) and directors of 80 different agencies to which they referred
      clients for parenting support services (56% response rate). Respondents indicated
      the types of parenting support services they provided and the clientele they
      served. RESULTS: The most common parenting support service in mental health
      agencies was referral to another agency. Individuals with mental disorders were
      eligible for services at the referral agencies on a case-by-case basis, and few
      agencies had programs for children. Parenting services were associated with the
      number of staff in the agency and with offering programs in urban or both urban
      and rural locations, which perhaps also indicates larger size of the
      organization. Agencies served fathers and mothers approximately equally, but
      child care was uncommon. CONCLUSIONS: Integrated clinical services for parents
      living with mental disorders are lacking. Such services should be designed to
      treat mental health as well as provide parenting skills intervention and
      practical support for parents, consistent with a recovery model.

PMID- 24684184
TI  - Targeting the epidermal growth factor receptor in solid tumors: focus on safety.
AB  - INTRODUCTION: Inhibition of the EGFR has emerged as a promising anticancer
      strategy, offering improved efficacy and quality of life for patients affected by
      tumors. The overall level of toxicity associated with EGFR inhibitors is low
      compared to other chemotherapy drugs, although they are commonly associated with
      skin and gastrointestinal adverse events. Thus, patients' quality of life may be
      considerably affected both by a physical and a psychosocial perspective. Adverse
      events that lead to treatment interruption or cessation may significantly
      compromise their outcome. AREAS COVERED: This review summarizes the
      characteristics of the distinctive toxicities of drugs targeting EGFR, addressing
      their incidence, pathophysiology and clinical presentation with a focus on the
      management of skin rash and other relevant adverse events, according to the
      available clinical evidence. Data regarding the correlation between the
      development of skin rash and clinical outcome are also reported. EXPERT OPINION:
      Drugs targeting EGFR are associated with a lower overall incidence of systemic
      side effects compared to standard chemotherapeutic agents; nevertheless, an
      increased risk of distinct toxicities that may affect patient's quality of life
      and anticancer treatment compliance is observed. Thus, clinical training projects
      directed toward a more accurate knowledge of such adverse events are essential to
      maximize the progress of targeted therapies against cancer.

PMID- 24684185
TI  - Melatonin protects testes against lithium-pilocarpine-induced temporal lobe
      epilepsy in rats: a time course study.
AB  - Male dysfunction is common in patients with temporal lobe epilepsy (TLE). We
      evaluated whether melatonin, as a supplement, can play a positive role in
      reducing the epileptogenesis imposing abnormalities of spermatozoa and testes in
      epileptic rats. Status epilepticus was induced based on the TLE lithium
      pilocarpine model. Two patterns of melatonin were administered to the epileptic
      animals along the mean durations of latent (14 days) and chronic (60 days)
      phases. Sperm parameters, different antioxidant enzyme levels, germ cell
      apoptosis, body and relative sex organ weights were evaluated in all groups 60
      days following SE induction. Chronic TLE caused a significant reduction in sperm
      parameters. In the testis, the reduced level of antioxidant enzymes was
      accompanied by a significant increase in malondialdehyde concentration. The
      presence of oxidant condition in the testes of epileptic animals caused expanded
      apoptosis in the germ cell layer. Moreover, the amount of weight gain in
      epileptic animals was more prominent. Melatonin administration was able to
      improve sperm motility by increasing the total antioxidant level. There was also
      a significant reduction in the spermatogenic cell line apoptosis and the extra
      weight gain of melatonin-treated animals. Melatonin supplementation might be
      considered as an acceptable cotreatment in epileptic patients. 

PMID- 24684186
TI  - Neurofilament heavy chain as a marker of neuroaxonal pathology and prognosis in
      acute encephalitis.
AB  - BACKGROUND AND PURPOSE: The neurological outcome of acute encephalitis can be
      devastating and early prognosis remains difficult. Biomarkers that quantify the
      extent of early brain injury are needed to improve the prognostic accuracy and
      aid patient management. Our objective was to assess whether cerebrospinal fluid
      (CSF) protein biomarkers of neuroaxonal and glial cell injury are elevated in
      distinct forms of acute encephalitis and predictive of poor outcome. METHODS:
      This was a prospective study of patients presenting with acute encephalitis to
      three teaching hospitals in London, UK. Levels of neurofilament heavy chain (NfH,
      SMI35) and S100B were quantified in CSF using enzyme-linked immunosorbent assay.
      The outcome was assessed by the Glasgow Outcome Scale (GOS). RESULTS: Fifty-six
      patients with acute encephalitis were recruited and classified into the following
      diagnostic categories: infectious (n = 20), inflammatory (n = 14) and unknown
      etiology (n = 22). Pathological levels of NfH and S100B were observed in 24/56
      (43%) and 54/56 (96%), respectively. Patients with infectious encephalitis had
      significantly higher NfH levels compared with the other two groups (P < 0.05). A
      poor outcome (GOS < 5) was associated with significantly higher CSF NfH levels
      within samples taken 2 weeks after symptom onset. CONCLUSIONS: This study
      suggests that longitudinal CSF NfH levels are of superior prognostic value
      compared with CSF S100B levels. Prolonged release of NfH, a marker of neuroaxonal
      damage, was associated with poor outcome. Potentially there is a window of
      opportunity for future neuroprotective treatment strategies in encephalitis.

PMID- 24684187
TI  - Follow the plume: the habitability of Enceladus.
AB  - The astrobiological exploration of other worlds in our Solar System is moving
      from initial exploration to more focused astrobiology missions. In this context,
      we present the case that the plume of Enceladus currently represents the best
      astrobiology target in the Solar System. Analysis of the plume by the Cassini
      mission indicates that the steady plume derives from a subsurface liquid water
      reservoir that contains organic carbon, biologically available nitrogen, redox
      energy sources, and inorganic salts. Furthermore, samples from the plume jetting
      out into space are accessible to a low-cost flyby mission. No other world has
      such well-studied indications of habitable conditions. Thus, the science goals
      that would motivate an Enceladus mission are more advanced than for any other
      Solar System body. The goals of such a mission must go beyond further geophysical
      characterization, extending to the search for biomolecular evidence of life in
      the organic-rich plume. This will require improved in situ investigations and a
      sample return.

PMID- 24684189
TI  - Is primary surgery of breast cancer patients consistent with German guidelines?
      Twelve-year trend of population-based clinical cancer registry data.
AB  - This population-based analysis aimed to describe the 12-year trend of primary
      surgery following the introduction of national guidelines for the management of
      breast cancer in Germany, thus the implementation of breast-conserving surgery
      (BCS) for pT1/2-tumours and the implementation of sentinel lymph node biopsy
      (SLNB). Cancer registry data from 72 742 breast cancer patients diagnosed between
      1999 and 2010 in four different regions in Germany were used. Descriptive
      statistics and multivariate logistic regression analysis were conducted. Between
      1999 and 2010, rates of BCS for pT1/2-tumours rose from 60.5% to 79.9%, rates of
      SLNB increased rapidly from 0.4% to 79.0%. Both surgical therapies were already
      adherent to the respective guidelines, although some regional differences could
      be observed: in 1999-2003, the chance of BCS was 2.6-fold higher [odds ratio (OR)
      2.6] in the western regions than in the eastern regions, but this difference
      decreased over time (2004-2007 OR 1.6; 2008-2010 OR 1.2). A similar pattern was
      observable for SLNB: in 1999-2003, the chance of receiving SLNB was 4.4-fold
      higher in the western regions, but these rates converged (2004-2007 OR 3.7; 2008
      2010 OR 1.5). The further increase of BCS- and SLNB rates after publication of
      guidelines and the reduction of regional differences may also be attributable to
      guideline implementation.

PMID- 24684188
TI  - Ethnic differences in the developmental significance of parentification.
AB  - Using an ecological framework, this 2-wave longitudinal study examined the
      effects of parentification on youth adjustment across the transition to
      adolescence in a high-risk, low-income sample of African American (58%) and
      European American (42%) mother-child dyads (T1 Mage = 10.17 years, T2 Mage =
      14.89 years; 52.4% female). Children's provision of family caregiving was
      moderately stable from early to late adolescence. Emotional and instrumental
      parentification evidenced distinct long-term effects on adolescents'
      psychopathology and the quality of the parent-child relationship. Ethnicity
      moderated these relations. Emotional and instrumental parentification behaviors
      were associated with predominantly negative outcomes among European American
      youth in the form of increased externalizing behavior problems and decreased
      parent-child relationship quality, whereas emotional parentification was
      associated with positive outcomes among African American youth in the form of
      increased parent-child relationship quality, and instrumental parentification was
      neutral. These findings support a multidimensional view of parentification as a
      set of culturally embedded phenomena whose effects can only be understood in
      consideration of the context in which they occur.

PMID- 24684190
TI  - Binding of the RNA chaperone Hfq to the type IV pilus base is crucial for its
      function in Synechocystis sp. PCC 6803.
AB  - The bacterial RNA-binding protein Hfq functions in post-transcriptional
      regulation of gene expression. There is evidence in a range of bacteria for
      specific subcellular localization of Hfq; however, the mechanism and role of Hfq
      localization remain unclear. Cyanobacteria harbour a subfamily of Hfq that is
      structurally conserved but exhibits divergent RNA binding sites. Mutational
      analysis in the cyanobacterium Synechocystis sp. PCC 6803 revealed that several
      conserved amino acids on the proximal side of the Hfq hexamer are crucial not
      only for Hfq-dependent RNA accumulation but also for phototaxis, the latter of
      which depends on type IV pili. Co-immunoprecipitation and yeast two-hybrid
      analysis show that the secretion ATPase PilB1 (a component of the type IV pilus
      base) is an interaction partner of Hfq. Fluorescence microscopy revealed that Hfq
      is localized to the cytoplasmic membrane in a PilB1-dependent manner.
      Concomitantly, Hfq-dependent RNA accumulation is abrogated in a DeltapilB1
      mutant, indicating that localization to the pilus base via interaction with PilB1
      is essential for Hfq function in cyanobacteria. 

PMID- 24684191
TI  - Comparative study of sensitivity, linearity, and resistance to inhibition of
      digital and nondigital polymerase chain reaction and loop mediated isothermal
      amplification assays for quantification of human cytomegalovirus.
AB  - Performing nucleic acid amplification techniques (NAATs) in digital format using
      limiting dilution provides potential advantages that have recently been
      demonstrated with digital polymerase chain reaction (dPCR). Key benefits that
      have been claimed are the ability to quantify nucleic acids without the need of
      an external calibrator and a greater resistance to inhibitors than real-time
      quantitative PCR (qPCR). In this study, we evaluated the performance of four
      NAATs, qPCR, dPCR, real-time quantitative loop mediated isothermal amplification
      (qLAMP), and digital LAMP (dLAMP), for the detection and quantification of human
      cytomegalovirus (hCMV). We used various DNA templates and inhibitors to compare
      the performance of these methods using a conventional real-time thermocycler
      platform (Bio-Rad CFX96) and a chip based digital platform (Fluidigm Biomark
      12.765 Digital Array). dPCR performed well and demonstrated greater resistance to
      inhibitors than the other methods although this resistance did not apply equally
      to all inhibitors tested. dLAMP was found to be less sensitive than dPCR, but its
      quantitative performance was better than qLAMP, the latter being unable to
      quantify below 1000 copies. dLAMP was also more resistant to inhibitors than
      qLAMP. Unlike qPCR, both digital methods were able to quantify viral genomes
      without requiring a calibrator; however, neither can currently compete with the
      large reaction volumes, and thus the greater absolute sensitivity, of qPCR. With
      the introduction of digital instrumentation that will enable larger reaction
      volumes, digital amplification methods such as those evaluated in this study
      could potentially offer a robust alternative to qPCR for nucleic acid
      quantification. 

PMID- 24684193
TI  - Elevating the quality of disability and rehabilitation research: mandatory use of
      the reporting guidelines.

PMID- 24684194
TI  - Neck pain: dry needling can decrease pain and increase motion.

PMID- 24684195
TI  - Upper extremity deep venous thrombosis.
AB  - The patient was a 34-year-old man currently serving in the military who was
      referred to a physical therapist by his primary care physician for a chief
      complaint of worsening right shoulder pain and paresthesias of the first, second,
      and third digits of his right hand, as well as right upper extremity swelling.
      Doppler ultrasonography was performed, and the presence of an occlusive thrombus
      in the right distal subclavian and axillary veins was revealed.

PMID- 24684197
TI  - A new pressure ulcer conceptual framework.
AB  - AIM: This paper discusses the critical determinants of pressure ulcer development
      and proposes a new pressure ulcer conceptual framework. BACKGROUND: Recent work
      to develop and validate a new evidence-based pressure ulcer risk assessment
      framework was undertaken. This formed part of a Pressure UlceR Programme Of
      reSEarch (RP-PG-0407-10056), funded by the National Institute for Health
      Research. The foundation for the risk assessment component incorporated a
      systematic review and a consensus study that highlighted the need to propose a
      new conceptual framework. DESIGN: Discussion Paper. DATA SOURCES: The new
      conceptual framework links evidence from biomechanical, physiological and
      epidemiological evidence, through use of data from a systematic review (search
      conducted March 2010), a consensus study (conducted December 2010-2011) and an
      international expert group meeting (conducted December 2011). IMPLICATIONS FOR
      NURSING: A new pressure ulcer conceptual framework incorporating key
      physiological and biomechanical components and their impact on internal strains,
      stresses and damage thresholds is proposed. Direct and key indirect causal
      factors suggested in a theoretical causal pathway are mapped to the physiological
      and biomechanical components of the framework. The new proposed conceptual
      framework provides the basis for understanding the critical determinants of
      pressure ulcer development and has the potential to influence risk assessment
      guidance and practice. It could also be used to underpin future research to
      explore the role of individual risk factors conceptually and operationally.
      CONCLUSION: By integrating existing knowledge from epidemiological, physiological
      and biomechanical evidence, a theoretical causal pathway and new conceptual
      framework are proposed with potential implications for practice and research.

PMID- 24684198
TI  - Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and
      Dresden, Germany.
AB  - BACKGROUND: There is a perpetuating increase in melanoma and basal cell carcinoma
      (BCC) incidence in Europe. Few studies are evaluating various risk factors for
      both tumours. OBJECTIVES: This pre-planned additional analysis directly compared
      occupational and past-time ultraviolet exposure behaviour, and examined the
      effects of sun sensitivity between melanoma and sporadic BCC, and assessed its
      importance for the two entities. PATIENTS/METHODS: The study included 503
      patients (melanoma, n = 291 and BCC, n = 212), and 329 controls from Germany. In
      all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age
      melanoma, 55 years; BCC, 69 years; and controls, 57 years). Selection of
      important risk factors was performed by backward elimination in a polytomous
      logistic regression. RESULTS: When directly comparing melanoma and sporadic BCC,
      actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with
      a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20 years
      before diagnosis, farming full time, sunbed use in general, seborrheic keratosis,
      actinic cheilitis, actinic keratosis and age were associated with a higher risk
      of sporadic BCC. Gardening 20 years before melanoma, hair colour and solar
      lentigo were risk factors for both entities. A re-evaluation of the data
      excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo
      maligna melanoma) resulted in selection of the same factors. However, compared to
      controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI
      0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was
      associated with a higher risk of sporadic BCC compared to melanoma. CONCLUSION:
      The odds for having clinical actinic elastosis was lower in BCC compared to
      melanoma. In contrast, various factors associated with chronic UV exposure and
      age had higher odds for sporadic BCC, rather than melanoma. Further research is
      required to set the context for these findings, especially regarding, atopy in
      non-lentiginous vs. lentiginous forms of melanoma, and possible molecular
      pathways involved.

PMID- 24684200
TI  - Do we need to worry about mycophenolate overdose?
AB  - INTRODUCTION: To discuss the significance of the recent observational case series
      from the Swiss Toxicological Information Centre (STIC). Mycophenolic acid (MPA)
      and its prodrug mycophenolate mofetil are immunosuppressive agents that are
      frequently prescribed in renal transplant recipients, and their safety profiles
      must be established. AREAS COVERED: This case series and systemic literature
      analysis consists of 15 cases of MPA overdose from the STIC and a systemic
      analysis of the literature over the past 18 years. This study focuses on acute
      overdosing, the effects of which are presumably mild. In contrast, the effects of
      long-term overdosing may be much more severe. Substantial underreporting is
      likely. The pharmacokinetic monitoring of MPA is rarely performed, which is both
      striking and does not coincide with findings in academic literature. The scant
      data on pharmacokinetic monitoring presented demonstrated that MPA has a short
      terminal half-life, which suggests that decontamination and activated charcoal
      treatment in acute overdose may not be necessary. EXPERT OPINION: The case series
      and systematic literature analysis of acute mycophenolate overdose represent an
      important contribution toward increasing the safety of MPA therapy.

PMID- 24684199
TI  - Lipidomics reveals a link between CYP1B1 and SCD1 in promoting obesity.
AB  - Cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of xenobiotic
      compounds and endogenous metabolites. Disruption of Cyp1b1 in mice results in
      suppression of high-fat diet (HFD)-induced obesity and an extensive change in
      hepatic energy regulation despite minimal constitutive expression of CYP1B1 in
      hepatocytes. Lack of CYP1B1 is correlated with altered lipid metabolism,
      especially lysophosphatidylcholines, contributing to protection against obesity.
      Ultraperformance liquid chromatography coupled to electrospray ionization
      quadrupole mass spectrometry (UPLC-ESI-QTOFMS)-based metabolomics revealed
      lysophosphatidylcholine 18:0 (LPC 18:0) as a biomarker positively related to HFD
      induced obesity. The increased serum LPC 18:0 in wild-type mice is reduced in
      Cyp1b1-null mice on a HFD, which is reversed in CYP1B1-humanized mice. CYP1B1
      humanized mice show higher diet-induced obesity compared with Cyp1b1-null mice,
      suggesting that human CYP1B1 shows a similar response to HFD as mouse Cyp1b1. In
      addition, hepatic stearoyl-CoA desaturase 1 (SCD1) expression was decreased in
      Cyp1b1-null mice, and the attenuated diet-induced obesity and lower serum LPC
      18:0 in the Cyp1b1-null mice is elevated after SCD1 overexpression, suggesting
      that SCD1 is correlated with CYP1B1-induced obesity. These studies establish a
      biochemical link between cytochromes P450, lipids, and metabolic disorders and
      suggest that inhibition of CYP1B1 could be target for antiobesity drugs. 

PMID- 24684201
TI  - Comment on Sallander et al. 'Vitamin D levels after UVB radiation: effects by UVA
      additions in a randomized controlled trial'.

PMID- 24684202
TI  - Two new natural products from Croton kongensis Gagnep.
AB  - A new diterpenoid, 14beta-hydroxy-3-oxo-ent-kaur-16-ene (1), and a new nor
      lignan, 8S-( - )-8-(4-hydroxy-3-methoxybenzoyl)-dihydrofuran-8(8'H)-one (4),
      along with five known compounds were isolated from the twigs and leaves of Croton
      kongensis Gagnep. Their isolations were clarified and structures were elucidated
      by the extensive spectroscopic analyses, especially 2D NMR experiments. 

PMID- 24684203
TI  - Cross-dehydrogenative couplings between indoles and beta-keto esters: ligand
      assisted ligand tautomerization and dehydrogenation via a proton-assisted
      electron transfer to Pd(II).
AB  - Cross-dehydrogenative coupling reactions between beta-ketoesters and electron
      rich arenes, such as indoles, proceed with high regiochemical fidelity with a
      range of beta-ketoesters and indoles. The mechanism of the reaction between a
      prototypical beta-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and N
      methylindole has been studied experimentally by monitoring the temporal course of
      the reaction by (1)H NMR, kinetic isotope effect studies, and control
      experiments. DFT calculations have been carried out using a dispersion-corrected
      range-separated hybrid functional (omegaB97X-D) to explore the basic elementary
      steps of the catalytic cycle. The experimental results indicate that the reaction
      proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces
      an enone intermediate. The dehydrogenation is assisted by N-methylindole, which
      acts as a ligand for Pd(II). The computational studies agree with this
      conclusion, and identify the turnover-limiting step of the dehydrogenation step,
      which involves a change in the coordination mode of the beta-keto ester ligand
      from an O,O'-chelate to an alpha-C-bound Pd enolate. This ligand tautomerization
      event is assisted by the pi-bound indole ligand. Subsequent scission of the beta'
      C-H bond takes place via a proton-assisted electron transfer mechanism, where
      Pd(II) acts as an electron sink and the trifluoroacetate ligand acts as a proton
      acceptor, to produce the Pd(0) complex of the enone intermediate. The coupling is
      completed in cycle B, where the enone is coupled with indole. Pd(TFA)2 and TFA
      catalyzed pathways were examined experimentally and computationally for this
      cycle, and both were found to be viable routes for the coupling step. 

PMID- 24684204
TI  - Demography, baseline disease characteristics and treatment history of patients
      with psoriasis enrolled in a multicentre, prospective, disease-based registry
      (PSOLAR).
AB  - BACKGROUND: Psoriasis is associated with several comorbidities and behavioural
      risk factors. OBJECTIVES: To evaluate demographic and disease characteristics in
      patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).
      METHODS: PSOLAR is a global, prospective, longitudinal, disease-based registry
      that includes a postmarketing commitment to evaluate safety in patients with
      psoriasis. Enrolled patients had to be receiving, or be eligible to receive,
      conventional systemic or biological agents. Demographic/disease characteristics,
      medical histories, lifestyle risk factors and previous treatments are collected
      at enrolment. Efficacy and safety data are collected every 6 months for 8 years,
      and data are extracted annually. Selected parameters are evaluated by age
      quartile using post hoc analyses. RESULTS: As of 23 August 2012, 11 900 patients
      were enrolled at 301 sites in North America, Europe and Latin America. Over half
      of the PSOLAR population (54.7%) is male, with a mean age of 48.6 years and mean
      body mass index of 30.9 kg m(-2) at enrolment. Mean duration of disease at
      enrolment was 17.5 years, and mean Physician's Global Assessment score was 2.0.
      Psoriatic arthritis (35.5%) and cardiovascular diseases (38.2%) were highly
      prevalent. Diabetes mellitus type II was reported in 11.4% of patients.
      Depression and anxiety were noted in 14.7% and 11.1% of patients, respectively;
      79.0% reported any alcohol use and 56.7% reported smoking or a history of
      smoking. The occurrence of most comorbidities, including cardiovascular disease
      and risk factors, increased with age. CONCLUSIONS: In the PSOLAR population,
      multiple and age-appropriate comorbidities are associated with psoriasis and may
      affect the selection of psoriasis treatments.

PMID- 24684205
TI  - Systems biology and proteomic analysis of cerebral cavernous malformation.
AB  - Cerebral cavernous malformations (CCM) are vascular anomalies caused by mutations
      in genes encoding KRIT1, OSM and PDCD10 proteins causing hemorrhagic stroke. We
      examine proteomic change of loss of CCM gene expression. Using human umbilical
      vein endothelial cells, label-free differential protein expression analysis with
      multidimensional liquid chromatography/tandem mass spectrometry was applied to
      three CCM protein knockdown cell lines and two control cell lines:
      ProteomeXchange identifier PXD000362. Principle component and cluster analyses
      were used to examine the differentially expressed proteins associated with CCM.
      The results from the five cell lines revealed 290 and 192 differentially
      expressed proteins (p < 0.005 and p < 0.001, respectively). Most commonly
      affected proteins were cytoskeleton-associated proteins, in particular myosin-9.
      Canonical genetic pathway analysis suggests that CCM may be a result of defective
      cell-cell interaction through dysregulation of cytoskeletal associated proteins.
      CONCLUSION: The work explores signaling pathways that may elucidate early
      detection and novel therapy for CCM.

PMID- 24684206
TI  - Measuring symptoms of post-traumatic stress disorder in people with intellectual
      disabilities: the development and psychometric properties of the Impact of Event
      Scale-Intellectual Disabilities (IES-IDs).
AB  - BACKGROUND: The aims of the study were to (1) revise the Impact of Event Scale
      Revised for use with people with intellectual disabilities (IDs), creating the
      Impact of Event Scale-Intellectual Disabilities (IES-IDs), (2) assess the
      reliability of the IES-IDs, and (3) compare the IES-IDs to an existing measure
      trauma-related symptomatology, namely the Lancaster and Northgate Trauma Scale
      (LANTS), along with measures of anxiety and depression. METHODS: Forty adults
      with IDs who had experienced at least one traumatic event were recruited and
      completed the IES-IDs and the LANTS on two occasions, separated by 2 weeks.
      Participants also completed the Glasgow Depression Scale and the Glasgow Anxiety
      Scale, along with the Trauma Information Form which was used to collect
      information about trauma history. RESULTS: Fifteen per cent of the sample had
      encountered five or more traumatic events. The IES-IDs and the LANTS had good to
      excellent internal consistency and test-retest reliability. Both measures
      correlated with self-report measures of depression and anxiety, although the
      strength of this correlation was greater with the LANTS. There was a significant
      positive correlation between trauma frequency and the IES-IDs, while trauma
      frequency did not correlate with the LANTS. CONCLUSIONS: Both the IES-IDs and the
      LANTS appear to have good reliability. PRACTITIONER POINTS: There is a lack of
      well-developed questionnaires that can be used to assess symptoms of post
      traumatic stress disorder (PTSD) in people with intellectual disabilities. The
      Impact of Event Scale-Revised was augmented creating the Impact of Event Scale
      Intellectual Disabilities (IES-IDs). The IES-IDs was shown to have good
      psychometric properties. The IES-IDs was compared to the Lancaster and Northgate
      Trauma Scale (LANTS), but the LANTS did not correlate with trauma frequency.
      However, this study had a small sample size, and a much larger study is needed to
      examine the factor structure of both the IES-IDs and the LANTS. Future studies
      should attempt to recruit people with IDs who have a diagnosis of PTSD.

PMID- 24684207
TI  - Strong extrinsic reproductive isolation between parapatric populations of an
      Australian groundsel.
AB  - Speciation with gene flow, or the evolution of reproductive isolation between
      interbreeding populations, remains a controversial problem in evolution. This is
      because gene flow erodes the adaptive differences that selection creates between
      populations. Here, we use a combination of common garden experiments in the field
      and in the glasshouse to investigate what ecological and genetic mechanisms
      prevent gene flow and maintain morphological and genetic differentiation between
      coastal parapatric populations of the Australian groundsel Senecio lautus. We
      discovered that in each habitat extrinsic reproductive barriers prevented gene
      flow, whereas intrinsic barriers in F1 hybrids were weak. In the field,
      herbivores played a major role in preventing gene flow, but glasshouse
      experiments demonstrated that soil type also created variable selective pressures
      both locally and on a greater geographic scale. Our experimental results
      demonstrate that interfertile plant populations adapting to contrasting
      environments may diverge as a consequence of concurrent natural selection acting
      against migrants and hybrids through multiple mechanisms. These results provide
      novel insights into the consequences of local adaptation in the origin of strong
      barriers to gene flow in plants, and suggest that herbivory may play an important
      role in the early stages of plant speciation. 

PMID- 24684208
TI  - Reliable cell segmentation based on spectral phasor analysis of hyperspectral
      stimulated Raman scattering imaging data.
AB  - Hyperspectral stimulated Raman scattering (SRS) imaging has rapidly become an
      emerging tool for high content analyses of cell and tissue systems. The label
      free nature of SRS imaging combined with its chemical specificity allows in situ
      and in vivo biochemical quantification at submicrometer resolution without
      sectioning and staining. Current hyperspectral SRS data analysis methods are
      based on either linear unmixing or multivariate analysis, which are not sensitive
      to small spectral variations and often provide obscure information on the cell
      composition. Here, we demonstrate a spectral phasor analysis method that allows
      fast and reliable cellular organelle segmentation of mammalian cells, without any
      a priori knowledge of their composition or basis spectra. We further show that,
      in combination with a branch-bound algorithm for optimal selection of a few
      wavenumbers, spectral phasor analysis provides a robust solution to label-free
      single cell analysis. 

PMID- 24684209
TI  - Asymmetric fluorination of alpha-branched cyclohexanones enabled by a combination
      of chiral anion phase-transfer catalysis and enamine catalysis using protected
      amino acids.
AB  - We report a study involving the successful merger of two separate chiral
      catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate
      Selectfluor and an enamine activation cycle, using a protected amino acid as
      organocatalyst. We have demonstrated the viability of this approach with the
      direct asymmetric fluorination of alpha-substituted cyclohexanones to generate
      quaternary fluorine-containing stereocenters. With these two chiral catalytic
      cycles operating together in a matched sense, high enantioselectivites can be
      achieved, and we envisage that this dual catalysis method has the potential to be
      more broadly applicable, given the breadth of enamine catalysis. It also
      represents a rare example of chiral enamine catalysis operating successfully on
      alpha-branched ketones, substrates commonly inert to this activation mode. 

PMID- 24684210
TI  - The biosurfactant viscosin produced by Pseudomonas fluorescens SBW25 aids
      spreading motility and plant growth promotion.
AB  - Food security depends on enhancing production and reducing loss to pests and
      pathogens. A promising alternative to agrochemicals is the use of plant growth
      promoting rhizobacteria (PGPR), which are commonly associated with many, if not
      all, plant species. However, exploiting the benefits of PGPRs requires knowledge
      of bacterial function and an in-depth understanding of plant-bacteria
      associations. Motility is important for colonization efficiency and microbial
      fitness in the plant environment, but the mechanisms employed by bacteria on and
      around plants are not well understood. We describe and investigate an atypical
      mode of motility in Pseudomonas fluorescens SBW25 that was revealed only after
      flagellum production was eliminated by deletion of the master regulator fleQ. Our
      results suggest that this 'spidery spreading' is a type of surface motility.
      Transposon mutagenesis of SBW25DeltafleQ (SBW25Q) produced mutants, defective in
      viscosin production, and surface spreading was also abolished. Genetic analysis
      indicated growth-dependency, production of viscosin, and several potential
      regulatory and secretory systems involved in the spidery spreading phenotype.
      Moreover, viscosin both increases efficiency of surface spreading over the plant
      root and protects germinating seedlings in soil infected with the plant pathogen
      Pythium. Thus, viscosin could be a useful target for biotechnological development
      of plant growth promotion agents.

PMID- 24684211
TI  - Oral doxycycline for Lyme neuroborreliosis with symptoms of encephalitis,
      myelitis, vasculitis or intracranial hypertension.
AB  - BACKGROUND AND PURPOSE: The treatment recommendation for Lyme neuroborreliosis
      with central nervous system (CNS) symptoms is intravenous ceftriaxone, according
      to current American and European guidelines. For Lyme neuroborreliosis with
      peripheral nervous system (PNS) symptoms, treatment with intravenous ceftriaxone
      and oral doxycycline is considered equally effective. The purpose of this study
      was to evaluate the efficacy of oral doxycycline in the treatment of Lyme
      neuroborreliosis with CNS symptoms. METHODS: Patients with Lyme neuroborreliosis
      who had undergone cerebrospinal fluid (CSF) sampling before and after treatment
      at the Department of Infectious Diseases, Sahlgrenska University Hospital, during
      the period 1990-2012, were included in this retrospective study. The CSF
      mononuclear cell count was used as a surrogate marker of treatment outcome.
      Comparisons of CSF mononuclear cell counts were made between patients with CNS
      symptoms and patients with PNS symptoms before and after treatment with oral
      doxycycline. RESULTS: Twenty-six patients classified as having CNS symptoms and
      115 patients classified as having PNS symptoms were included. The decline in CSF
      mononuclear cell counts did not differ significantly between the two groups of
      patients. All patients with CNS disease showed a marked clinical improvement
      after treatment, even though 62% had remaining symptoms at the end of follow-up.
      CONCLUSION: Treatment with oral doxycycline resulted in a similar decrease in CSF
      mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms
      compared with patients with Lyme neuroborreliosis with PNS symptoms. The results
      indicate that oral doxycycline is an effective treatment for Lyme
      neuroborreliosis irrespective of the severity of symptoms.

PMID- 24684212
TI  - Focused groundwater controlled feedbacks into the hyporheic zone during baseflow
      recession.
AB  - Groundwater surface water interaction in the hyporheic zone remains an important
      challenge for water resources management and ecosystem restoration. In
      heterogeneous stratified glacial sediments, reach-scale environments contain an
      uneven distribution of focused groundwater flow occurring simultaneously with
      diffusely discharging groundwater. This results in a variation of stream-aquifer
      interactions, where focused flow systems are able to temporally dominate exchange
      processes. The research presented here investigates the direct and indirect
      influences focused groundwater discharge exerts on the hyporheic zone during
      baseflow recession. Field results demonstrate that as diffuse sources of
      groundwater deplete during baseflow recession, focused groundwater discharge
      remains constant. During baseflow recession the hyporheic zone is unable to
      expand, while the high nitrate concentration from focused discharge changes the
      chemistry of the stream. The final result is a higher concentration of nitrate in
      the hyporheic zone as this altered surface water infiltrates into the subsurface.
      This indirect coupling of focused groundwater discharge and the hyporheic zone is
      unaccounted for in hyporheic studies at this time. Results indicate important
      implications for the potential reduction of agricultural degradation of water
      quality. 

PMID- 24684214
TI  - Malignancy rate in thyroid nodules classified as Bethesda category III
      (AUS/FLUS): Is there a correct answer?

PMID- 24684215
TI  - Quantum yields for photochemical production of NO2 from organic nitrates at
      tropospherically relevant wavelengths.
AB  - Absorption cross-sections and quantum yields for NO2 production (PhiNO2) are
      reported for gaseous methyl, ethyl, n-propyl, and isopropyl nitrate at 294 K.
      Absorption cross-sections in the wavelength range of 240-320 nm agree well with
      prior determinations. NO2 quantum yields at photoexcitation wavelengths of 290,
      295, and 315 nm are unity within experimental uncertainties for all of the alkyl
      nitrates studied and are independent of bath gas (N2) pressure for total sample
      pressures in the range of 250-700 Torr. When averaged over all wavelengths and
      sample pressures, values of PhiNO2 are 1.03 +/- 0.05 (methyl nitrate), 0.98 +/-
      0.09 (ethyl nitrate), 1.01 +/- 0.04 (n-propyl nitrate), and 1.00 +/- 0.05
      (isopropyl nitrate), with uncertainties corresponding to 1 standard deviation.
      Absorption cross-sections for ethyl nitrate, isopropyl nitrate, and two
      unsaturated dinitrate compounds, but-3-ene-1,2-diyl dinitrate and (Z)-but-2-ene
      1,4-diyl dinitrate in acetonitrile solution, are compared to gas-phase values,
      and over the wavelength range of 260-315 nm, the gas-phase values are well
      reproduced by dividing the liquid-phase cross-sections by 2.0, 1.6, 1.7, and 2.2,
      respectively. Reasonable estimates of the gas-phase absorption cross-sections for
      low-volatility organic nitrates can therefore be obtained by halving the values
      for acetonitrile solutions. The quantum yield for NO2 formation from
      photoexcitation of but-3-ene-1,2-diyl dinitrate at 290 nm is significantly lower
      than those for the alkyl (mono) nitrates: a best estimate of PhiNO2 <= 0.25 is
      obtained from the experimental measurements. 

PMID- 24684213
TI  - Potent and selective inhibitors of human reticulocyte 12/15-lipoxygenase as anti
      stroke therapies.
AB  - A key challenge facing drug discovery today is variability of the drug target
      between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes
      to ischemic brain injury, but its human and rodent isozymes have different
      inhibitor specificities. In the current work, we have utilized a quantitative
      high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype
      for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human
      12/15-LOX and is protective against oxidative glutamate toxicity in mouse
      neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity
      versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active
      site ferric ion. Lastly, 1 significantly reduced infarct size following permanent
      focal ischemia in a mouse model of ischemic stroke. As such, this represents the
      first report of a selective inhibitor of human 12/15-LOX with demonstrated in
      vivo activity in proof-of-concept mouse models of stroke. 

PMID- 24684216
TI  - Case of brain metastasis from second-relapsed pediatric hepatoblastoma.

PMID- 24684217
TI  - Effects of alpha1-adrenoceptor antagonist (tamsulosin) on incident of ejaculation
      and semen quality in the goat.
AB  - Male temporary contraception is occasionally required in some animals. Alpha1
      adrenoceptor antagonist (tamsulosin) can cause ejaculation disorder. Two sets of
      Latin square were applied to six male goats to received either normal saline,
      dimethylsulphoxide or tamsulosin (179.8 nmol kg(-1) ) at 1-week interval. Semen
      collection and libido scoring were undertaken at 3, 6 and 24 h post-injection.
      For ejaculated semen, its quality was evaluated. Physiological measurements
      including body temperature, respiration and heart rates were measured before
      injection and at 30 min before semen collection. The results showed that libido
      score and physiological changes were not affected by treatments and time periods.
      Anejaculation was observed in 11 (91.7%), 5 (41.7%) and 1 (8.3%) males at 3, 6
      and 24 h post-tamsulosin injection respectively. The incidence returned to normal
      when compared with control groups at 24 h. The percentages of motile and live
      spermatozoa at 6 h post-tamsulosin injection were significantly lower (P < 0.05)
      than that of normal saline group. At 24 h post-injection, there were no
      significant differences of all semen parameters among treatments. This study
      demonstrated that tamsulosin had temporary effects on ejaculation and semen
      quality without reducing sex desire and physiological functions in male goats. 

PMID- 24684218
TI  - When psychotherapy is indefinite and there is no final outcome: case study of a
      community mental health clinic.
AB  - Little is known about long-term patients for whom there is no anticipated
      endpoint to treatment. In this qualitative case study, we used a focus group
      methodology to understand how psychotherapists at a community mental health
      clinic work with low-income adult patients who are seen indefinitely. Narrative
      themes that emerged from the focus group discussion include the nature of these
      patients' diagnoses and life problems; the sociocultural contexts in which they
      live; the kinds of treatment goals and interventions; the internal and external
      barriers to termination; and how therapists recognize the need to work
      indefinitely with some patients to keep them alive or functioning in the
      community. Although a diagnosis of major mental illness was the foremost reason
      for not planning a termination, participants also mentioned working indefinitely
      with some higher functioning patients whose lives are perpetually in crisis.
      Participants emphasized the importance of having a compassionate clinical team
      and supportive administration for seeing patients indefinitely, even when third
      party payments end. Results are discussed in terms of their implications for
      service delivery as well as their implications for future investigations of
      psychotherapy that has no foreseeable endpoint.

PMID- 24684219
TI  - The insecure psychotherapy base: Using client and therapist attachment styles to
      understand the early alliance.
AB  - The purpose of this study was to test the notion that complementary attachments
      are best for achieving a secure base in psychotherapy. Specifically, we predicted
      third to fifth session alliance from client- and therapist-rated attachment style
      interactions. Using a combined sample of 46 therapy dyads from a community mental
      health clinic and university counseling center, the client- and therapist
      perceived therapy alliance, attachment anxiety, and attachment avoidance were
      examined at the beginning of therapy. The results of an Actor-Partner
      Interdependence Model (APIM; Kenny & Cook, 1999, Partner effects in relationship
      research: Conceptual issues, analytic difficulties, and illustrations. Personal
      Relationships, 6, 433-448.) indicated that there was no direct effect of either
      client or therapist attachment style on therapist or client early ratings of the
      alliance. One significant interaction emerged and indicated that client-perceived
      alliance was influenced by therapist and client attachment anxiety. The client
      perceived early alliance was higher when more anxious therapists worked with
      clients with decreasing anxiety. The client early alliance was higher when less
      anxious therapists worked with clients with increasing anxiety. The findings
      partially support the notion that different attachment configurations between the
      therapist and client facilitate greater alliance, but this was the case only when
      assessing client-perceived early alliance and only with regards to the dimension
      of attachment anxiety. There were no significant main effects or interactions
      when exploring therapist-perceived alliance. Implications of the findings are
      discussed along with recommendations for future study and clinical training.

PMID- 24684220
TI  - Treating the untreatable: a single case study of a psychopathic inpatient treated
      with schema therapy.
AB  - From its first conceptualization in modern psychiatry, psychopathy has been
      considered difficult if not impossible to treat. Schema Therapy (ST) is a
      psychotherapeutic approach that has shown efficacy in patients with borderline
      personality disorder. ST has recently been adapted for personality disordered
      forensic patients, including patients with high levels of psychopathy. The
      present case study examined the process of individual ST, combined with movement
      therapy and milieu therapy by the nursing staff, with a forensic inpatient with
      psychopathic features (Psychopathy Checklist-Revised total score = 28.4). The
      patient had been sentenced to a mandatory treatment order in relation to a sexual
      assault. We assessed change using independent assessments of psychopathic traits,
      cognitive schemas, and risk-related behaviors over the 4-year treatment period
      and a 3-year follow-up. We also assessed the quality of the working alliance.
      Reliable change analyses showed significant improvements in psychopathic traits,
      cognitive schemas, and risk-related outcomes. At 3 years posttreatment, the
      patient was living independently outside of the forensic institution without
      judicial supervision and he had not reoffended. While many questions remain about
      the effectiveness of psychotherapeutic treatment for psychopathic patients, our
      study challenges the view that they are untreatable.

PMID- 24684221
TI  - An empirical investigation of analytic process: contrasting a good and poor
      outcome case.
AB  - The aim of this article is to assess the difference in the analytic processes
      between two patients with similar personality profiles, who were in analysis
      during the same time, by two analysts with similar training and working in a
      similar setting. We explored patients' personality and changes with the Global
      Assessment of Functioning Scale (GAF; APA, 2000) and the Shedler-Westen
      Assessment Procedure-200 (SWAP-200; Westen & Shedler, 1999a, 1999b) applied by
      two pairs of independent raters in 16 sessions. In addition, we assessed
      therapeutic processes with the Analytic Process Scales (APS; Waldron, Scharf,
      Hurst, Firestein, & Burton, 2004b) and the Dynamic Interaction Scales (DIS;
      Waldron, Gazzillo, Genova, Lingiardi, 2013) applied by three independent raters
      to 20 sessions, as well as the Helping Alliance Rating Scale (HAR; Luborsky,
      Crits-Cristoph, Alexander, Margolis, & Cohen, 1983) applied to eight sessions
      from the beginning of each therapy. Our results showed striking differences
      between the outcomes of these two psychoanalyses that are paralleled by
      differences in their therapeutic process. We provide verbatim clinical
      interactions to illustrate these differences and explore the potential
      implications of these findings.

PMID- 24684222
TI  - Novice therapist attachment and perceived ruptures and repairs: a pilot study.
AB  - Although extensively discussed in theoretical articles, empirical studies of
      therapist attachment and perceptions of ruptures and repairs are lacking. The
      present study examined the relationship between therapist attachment anxiety and
      avoidance and their perceptions of rupture tension, effort, and repair. Twenty
      two novice therapists completed a measure of adult romantic attachment and a
      measure to assess perceptions of ruptures and repairs following the eighth
      session with their first clients. Results revealed that there was a strong
      positive correlation between therapist attachment anxiety and effort spent
      focused on perceived ruptures and a moderate positive correlation between
      attachment anxiety and rupture tension. There was no significant relationship
      between attachment anxiety and perceived repairs of ruptures. Attachment
      avoidance was not significantly correlated with either perceptions of the
      ruptures or repairs. Therapists who were higher on anxiety and avoidance, more
      fearful therapists, reported the most ruptures. Limitations and implications of
      the findings are presented.

PMID- 24684223
TI  - Postglacial expansion and not human influence best explains the population
      structure in the endangered kea (Nestor notabilis).
AB  - Inferring past demography is a central question in evolutionary and conservation
      biology. It is, however, sometimes challenging to infer the processes that shaped
      the current patterns of genetic variation in endangered species. Population
      substructuring can occur as a result of survival in several isolated refugia and
      subsequent recolonization processes or via genetic drift following a population
      decline. The kea (Nestor notabilis) is an endemic parrot widely distributed in
      the mountains of the South Island of New Zealand that has gone through a major
      human-induced population decline during the 1860s-1970s. The aims of this study
      were to understand the glacial and postglacial history of kea and to determine
      whether the recent population decline played a role in the shaping of the current
      genetic variation. We examined the distribution of genetic variation,
      differentiation and admixture in kea using 17 microsatellites and the
      mitochondrial control region. Mitochondrial data showed a shallow phylogeny and a
      genetic distinction between the North and South of the range consistent with the
      three genetic clusters identified with microsatellite data. Both marker types
      indicated an increase in genetic isolation by geographic distance. Approximate
      Bayesian Computation supported a scenario of postglacial divergence from a single
      ancestral glacial refugium, suggesting that the contemporary genetic structure
      has resulted from recolonization processes rather than from a recent population
      decline. The recent evolutionary origin of this genetic structure suggests that
      each genetic cluster does not need to be considered as independent conservation
      units. 

PMID- 24684224
TI  - Linear immunoglobulin A disease and vancomycin: two real ancestral enemies?

PMID- 24684226
TI  - Risk adapted therapy for multiple myeloma: back to basics.

PMID- 24684225
TI  - Predicting benefit from imatinib: are we close?

PMID- 24684227
TI  - A single institution experience of extranodal natural killer/T cell lymphoma of
      nasal type.
AB  - Extranodal natural killer/T cell lymphoma (ENKTL) nasal type is a rare form of
      non-Hodgkin lymphoma that is more commonly seen in Asia and Latin America than in
      North America or Europe. The purpose of this study was to determine the treatment
      outcomes with a combined modality approach and whether treatment outcomes varied
      according to ethnicity in patients with ENKTL, nasal type in Toronto, Canada.
      Patients presenting with ENKTL, nasal type, between 1994 and 2011 were
      retrospectively reviewed. Patient characteristics, including the patient's ethnic
      origin, treatment details and outcomes were recorded and analyzed for significant
      differences between Asian and Caucasian patients. A total of 34 patients were
      identified: 16 Asian, 16 Caucasian, one Aboriginal and one Hispanic. All patients
      had nasal cavity involvement. The majority had localized disease: stage I (n =
      22), stage II (n = 6); and stage IV in six patients. Combined radiotherapy (RT)
      and chemotherapy was intended for 32 of the 34 patients, with two receiving RT
      alone. Median RT dose was 45 Gy (range: 35-50.4 Gy). Response to initial
      treatment was observed in 44% of patients. Two-year disease-free survival was
      17.8% (Asian patients: 18.8%, Caucasians: 20%, p = 0.82), and overall survival
      39.2% (Asian patients: 30%, Caucasians: 42%, p = 0.52). There were no significant
      differences in clinical outcomes in terms of patient ethnicity. A combined
      modality approach (with cyclophosphamide, doxorubicin, vincristine, prednisone
      [CHOP] chemotherapy administered initially) is of limited effectiveness. We have
      now adopted the use of RT as the initial treatment approach, followed by
      multiagent chemotherapy.

PMID- 24684228
TI  - History of chronic comorbidity and risk of chemotherapy-induced febrile
      neutropenia in patients with non-Hodgkin lymphoma not receiving granulocyte
      colony-stimulating factor prophylaxis.
AB  - We conducted a cohort study to examine the association between a wide variety of
      chronic comorbidities and risk of febrile neutropenia (FN) in patients with non
      Hodgkin lymphoma (NHL) from 2000 to 2009 treated with chemotherapy at Kaiser
      Permanente Southern California. History of comorbidities and FN events were
      identified using electronic medical records. Cox model adjusting for propensity
      score was used to determine the association between a comorbid condition and FN.
      Models that additionally adjusted for cancer stage, baseline absolute neutrophil
      count, chemotherapy regimen and dose reduction were also evaluated. A total of
      2480 patients with NHL were included, and 60% received CHOP/R-CHOP
      (cyclophosphamide, doxorubicin, vincristine, prednisone, with or without
      rituximab). In total, 236 (9.5%) patients developed FN in the first chemotherapy
      cycle. Anemia (adjusted hazard ratio [HR] = 1.6, 95% confidence interval [1.2
      2.2]), HIV infection (HR = 3.8 [2.0-6.7]) and rheumatoid diseases (HR = 2.4 [1.3
      4.0]) were associated with significantly increased risk of FN. These results
      provide evidence that chronic comorbidity increases the risk of FN.

PMID- 24684229
TI  - Extreme thrombocytosis in chronic myeloid leukemia in the era of tyrosine kinase
      inhibitors.

PMID- 24684230
TI  - Analysis of interleukin-10 promoter single nucleotide polymorphisms and risk of
      non-Hodgkin lymphoma in a Malaysian population.
AB  - We evaluated the association of two IL10 single nucleotide polymorphisms (SNPs)
      (rs1800896 and rs1800871) with non-Hodgkin lymphoma (NHL) risk in the three major
      races of the Malaysian population (Malay, Chinese and Indian; 317 cases and 330
      controls). Our initial screening demonstrated that rs1800871 but not rs1800896
      was significantly associated with increased NHL risk in Malays (pMalay-Rec =
      0.007) and Chinese only (pChinese-Rec = 0.039). Subsequent combined analysis of
      the Malay and Chinese revealed significant association of rs1800871 with all
      (ALL) NHL subtypes (pMeta-ALL-NHL-Rec = 0.001), ALL B-cell subtypes (pMeta-ALL-B
      cell-Rec = 0.003), diffuse large B-cell lymphoma (DLBCL) subtype (pMeta-DLBCL-Rec
      = 0.002) and ALL T-cell subtypes (pMeta-ALL-T-cell-Rec = 0.031). SNP rs1800896
      showed increased risk only in follicular lymphoma (FL) (pMeta-FL-Dom = 0.0004).
      We also detected a male-specific association of rs1800871 with increased NHL risk
      (pMeta-Male-ALL-NHL-Rec = 0.006) in the combined analysis. To our knowledge, this
      is the first report on the association of IL10 promoter SNPs with NHL
      susceptibility in the three major races of Malaysia.

PMID- 24684231
TI  - Ectonucleoside triphosphate diphosphohydrolase-1 (E-NTPDase1/CD39) as a new
      prognostic marker in chronic lymphocytic leukemia.
AB  - Numerous prognostic markers were introduced to screen for patients with B-cell
      chronic lymphocytic leukemia (B-CLL) likely to have a progressive course, bearing
      the potential to facilitate risk-adapted treatment strategies. Extracellular
      adenosine triphosphate (ATP) functions as a "natural adjuvant" that boosts immune
      response in the tumor microenvironment. Ectonucleoside triphosphate
      diphosphohydrolase-1 (CD39/ENTPD1) is the ectonucleotidase that catalyzes the
      hydrolysis of ATP. The present study was conducted to analyze CD39 expression in
      T cells and B-CLL cells to evaluate its impact on the clinical course of patients
      with B-CLL and correlate its levels with well-established risk factors. T-cell
      CD39 expression was significantly increased in patients' peripheral blood
      compared to healthy controls. The higher levels were associated with advanced
      stages of disease and negatively interacted with time to first treatment.
      Overall, our data indicate that T-cell CD39 expression may identify subsets of
      patients with B-CLL with an unfavorable clinical outcome. Moreover, it can be
      incorporated into prognostic schema to improve the prediction of CLL disease
      progression.

PMID- 24684232
TI  - A comprehensive analysis of the geranylgeranylglyceryl phosphate synthase enzyme
      family identifies novel members and reveals mechanisms of substrate specificity
      and quaternary structure organization.
AB  - Geranylgeranylglyceryl phosphate synthase (GGGPS) family enzymes catalyse the
      formation of an ether bond between glycerol-1-phosphate and polyprenyl
      diphosphates. They are essential for the biosynthesis of archaeal membrane
      lipids, but also occur in bacterial species, albeit with unknown physiological
      function. It has been known that there exist two phylogenetic groups (I and II)
      of GGGPS family enzymes, but a comprehensive study has been missing. We therefore
      visualized the variability within the family by applying a sequence similarity
      network, and biochemically characterized 17 representative GGGPS family enzymes
      regarding their catalytic activities and substrate specificities. Moreover, we
      present the first crystal structures of group II archaeal and bacterial enzymes.
      Our analysis revealed that the previously uncharacterized bacterial enzymes from
      group II have GGGPS activity like the archaeal enzymes and differ from the
      bacterial group I enzymes that are heptaprenylglyceryl phosphate synthases. The
      length of the isoprenoid substrate is determined in group II GGGPS enzymes by
      'limiter residues' that are different from those in group I enzymes, as shown by
      site-directed mutagenesis. Most of the group II enzymes form hexamers. We could
      disrupt these hexamers to stable and catalytically active dimers by mutating a
      single amino acid that acts as an 'aromatic anchor'. 

PMID- 24684233
TI  - The zinc finger protein PtaZFP2 negatively controls stem growth and gene
      expression responsiveness to external mechanical loads in poplar.
AB  - Mechanical cues are essential signals regulating plant growth and development. In
      response to wind, trees develop a thigmomorphogenetic response characterized by a
      reduction in longitudinal growth, an increase in diameter growth, and changes in
      mechanical properties. The molecular mechanisms behind these processes are poorly
      understood. In poplar, PtaZFP2, a C2H2 transcription factor, is rapidly up
      regulated after stem bending. To investigate the function of PtaZFP2, we analyzed
      PtaZFP2-overexpressing poplars (Populus tremula * Populus alba). To unravel the
      genes downstream PtaZFP2, a transcriptomic analysis was performed. PtaZFP2
      overexpressing poplars showed longitudinal and cambial growth reductions together
      with an increase in the tangent and hardening plastic moduli. The regulation
      level of mechanoresponsive genes was much weaker after stem bending in PtaZFP2
      overexpressing poplars than in wild-type plants, showing that PtaZFP2 negatively
      modulates plant responsiveness to mechanical stimulation. Microarray analysis
      revealed a high proportion of down-regulated genes in PtaZFP2-overexpressing
      poplars. Among these genes, several were also shown to be regulated by mechanical
      stimulation. Our results confirmed the important role of PtaZFP2 during plant
      acclimation to mechanical load, in particular through a negative control of plant
      molecular responsiveness. This desensitization process could modulate the
      amplitude and duration of the plant response during recurrent stimuli.

PMID- 24684234
TI  - Interobserver variability in transient elastography analysis of patients with
      chronic hepatitis C.
AB  - BACKGROUND & AIMS: Transient elastography based on liver stiffness measurement is
      a non-invasive method to assess hepatic fibrosis. However, interobserver
      variability has led to controversy over its use in fibrosis evaluation. To
      evaluate the interobserver variation in transient elastography in chronic
      hepatitis C. METHODS: We performed a cross-sectional study, analysing findings
      from two experienced operators who each assessed 195 patients by transient
      elastography on the same day. Liver stiffness measurement used to define fibrosis
      stages, based on METAVIR score, was: <7.1 as F0F1, 7.1-9.4 as F2, 9.5-12.4, as F3
      and >12.4 kPa as F4. We also assessed interobserver variation in identification
      of potential oesophageal varices screening based on transient elastography.
      RESULTS: The interobserver intraclass correlation coefficient was 0.940 (95% CI
      0.863-0.967) and measurements made by operators correlated [Spearman's rho =
      0.924; P < 0.001]. However, the median liver stiffness measurement assessed by
      first operators was higher (11.5 vs 9.8 kPa; P < 0.001). The discordance between
      operators was 35% for at least one stage of fibrosis and 5% for two or more
      stages. Interobserver reliability values were kappa = 0.61 for fibrosis stages F
      >= 2 and kappa = 0.80 for cirrhosis. Among the 74 patients determined to have
      cirrhosis by at least one operator, there was considerable discordance in
      identification of those with indication for oesophageal varices screening (kappa
      values from 0.13 to 0.61) according to several cut-offs. CONCLUSION: Although a
      high correlation of liver stiffness measurement between operators, interobserver
      variability in transient elastography was not negligible. This method should not
      be used as the only screening tool for oesophageal varices in chronic hepatitis
      C.

PMID- 24684235
TI  - Rapid ligations with equimolar reactants in water with the potassium
      acyltrifluoroborate (KAT) amide formation.
AB  - The identification of fast, chemoselective bond-forming reactions is one of the
      major contemporary challenges in chemistry. We show that chemoselective amide
      forming ligations of potassium acyltrifluoroborates (KATs) and O
      carbamoylhydroxylamines proceed in the presence of all unprotected functional
      groups with a second-order rate constant of 20 M(-1) s(-1). PEG chains, lipids,
      biotin, and dyes were introduced onto an unprotected 31-mer peptide (a GLP-1
      analogue) with equimolar ratios of reactants within minutes at 1 mM and within 1
      h at 100 MUM, even with Mw 20,000 PEG. This conjugation reaction provides a new
      approach to the synthesis of molecules such as protein-protein and protein
      polymer conjugates.

PMID- 24684236
TI  - Penile tumours: a review.
AB  - Penile tumours are an important problem of male health affecting physical, mental
      and sexual health. Penile tumours can be subdivided into benign and malignant
      lesions. Their knowledge is important to prevent mutilating surgery in benign
      lesions. On the other hand, early recognition of malignancies is important for
      improved prognosis, and preservation of function. The most important tumour by
      epidemiology and prognosis is penile cancer. In contrast, malignant melanoma,
      sarcomas and lymphomas are rare. Clinical symptoms, histopathology and treatment
      options are discussed. Best possible treatment needs an interdisciplinary
      approach. 

PMID- 24684237
TI  - Age-associated differential microRNA levels in human follicular fluid reveal
      pathways potentially determining fertility and success of in vitro fertilization.
AB  - Reproductive life span and fertility have been shown to depend on successful
      early folliculogenesis, which involves cell-to-cell communication and the
      concerted regulation of gene expression at both the oocyte and granulosa cell
      levels. Recently, micro RNAs (miRNAs) were identified as fine-tuners of gene
      expression. Here, we report that miRNAs can readily be detected within membrane
      enclosed vesicles of human follicular fluid. MiRNA expression profiling of the
      follicular fluid of younger (<31 years) and older (>38 years) women revealed a
      set of four differentially expressed miRNAs. The predicted targets of these
      miRNAs are clearly enriched in genes involved in heparan-sulfate biosynthesis,
      extracellular matrix-receptor interaction, carbohydrate digestion and absorption,
      p53 signaling, and cytokine-cytokine-receptor interaction. Several of these
      pathways have been reported to be determinants of fertility, suggesting that this
      set of miRNAs and their respective targets should be evaluated in relation to
      reproductive aging and assisted reproduction.

PMID- 24684238
TI  - Privileged phosphine-based metal-organic frameworks for broad-scope asymmetric
      catalysis.
AB  - A robust and porous Zr metal-organic framework (MOF) based on a BINAP-derived
      dicarboxylate linker, BINAP-MOF, was synthesized and post-synthetically metalated
      with Ru and Rh complexes to afford highly enantioselective catalysts for
      important organic transformations. The Rh-functionalized MOF is not only highly
      enantioselective (up to >99% ee) but also 3 times as active as the homogeneous
      control. XAFS studies revealed that the Ru-functionalized MOF contains Ru-BINAP
      precatalysts with the same coordination environment as the homogeneous Ru
      complex. The post-synthetically metalated BINAP-MOFs provide a versatile family
      of single-site solid catalysts for catalyzing a broad scope of asymmetric organic
      transformations, including addition of aryl and alkyl groups to alpha,beta
      unsaturated ketones and hydrogenation of substituted alkene and carbonyl
      compounds. 

PMID- 24684239
TI  - Misdiagnosed CD19 deficiency leads to severe lung disease.

PMID- 24684240
TI  - Pharmacokinetic evaluation of vortioxetine for the treatment of major depressive
      disorder.
AB  - INTRODUCTION: Major depressive disorder (MDD), one of the most common disorders
      in medical practice and one of the leading causes of disability worldwide, is
      frequently comorbid with anxiety disorders. Vortioxetine (Lu AA21004) is a new
      antidepressant that combines a number of neurotransmitter reuptake and receptor
      effects that have been thought to predict efficacy as a treatment for depressive
      and anxiety disorders. AREAS COVERED: This review summarizes the pharmacology and
      neurobiology of vortioxetine. Studies of its efficacy and tolerability in major
      depression and generalized anxiety disorder are critically reviewed. EXPERT
      OPINION: Despite the fact that industry-sponsored studies are more likely than
      other clinical trials to support efficacy of the experimental drug, results have
      been mixed. Some studies supported that vortioxetine is superior to placebo in
      the treatment of MDD and some do not. Two studies supported the efficacy of
      vortioxetine in the treatment of generalized anxiety disorder and two do not. The
      incidence of sexual dysfunction has varied considerably in different studies, but
      cardiac effects and psychomotor impairment seem to be minimal. Advantages of
      vortioxetine over existing antidepressants are not yet clear.

PMID- 24684241
TI  - The potential for biologically catalyzed anaerobic methane oxidation on ancient
      Mars.
AB  - This study examines the potential for the biologically mediated anaerobic
      oxidation of methane (AOM) coupled to sulfate reduction on ancient Mars. Seven
      distinct fluids representative of putative martian groundwater were used to
      calculate Gibbs energy values in the presence of dissolved methane under a range
      of atmospheric CO2 partial pressures. In all scenarios, AOM is exergonic, ranging
      from -31 to -135 kJ/mol CH4. A reaction transport model was constructed to
      examine how environmentally relevant parameters such as advection velocity,
      reactant concentrations, and biomass production rate affect the spatial and
      temporal dependences of AOM reaction rates. Two geologically supported models for
      ancient martian AOM are presented: a sulfate-rich groundwater with methane
      produced from serpentinization by-products, and acid-sulfate fluids with methane
      from basalt alteration. The simulations presented in this study indicate that AOM
      could have been a feasible metabolism on ancient Mars, and fossil or isotopic
      evidence of this metabolic pathway may persist beneath the surface and in surface
      exposures of eroded ancient terrains.

PMID- 24684242
TI  - Identifying the emerging human pathogen Scedosporium prolificans by using a
      species-specific monoclonal antibody that binds to the melanin biosynthetic
      enzyme tetrahydroxynaphthalene reductase.
AB  - The dematiaceous (melanized) fungus Scedosporium prolificans is an emerging and
      frequently fatal pathogen of immunocompromised humans and which, along with the
      closely related fungi Pseudallescheria boydii, Scedosporium apiospermum and S.
      aurantiacum in the Pseudallescheria-Scedosporium complex, is a contributing
      aetiology to tsunami lung and central nervous system infections in near-drowning
      victims who have aspirated water laden with spores. At present, the natural
      habitat of the fungus is largely unknown, and accurate detection methods are
      needed to identify environmental reservoirs of infectious propagules. In this
      study, we report the development of a monoclonal antibody (mAb) (CA4) specific to
      S. prolificans, which does not cross-react with closely related fungi in the
      Pseudallescheria-Scedosporium complex or with a wide range of mould and yeast
      species pathogenic to humans. Using genome sequencing of a soil isolate and
      targeted gene disruption of the CA4 antigen-encoding gene, we show that mAb CA4
      binds to the melanin-biosynthetic enzyme tetrahydroxynaphthalene reductase.
      Enzyme-deficient mutants produce orange-brown or green-brown spore suspensions
      compared with the black spore suspension of the wild-type strain. Using mAb CA4
      and a mAb (HG12) specific to the related fungi P. boydii, P. apiosperma, S.
      apiospermum and S. aurantiacum, we demonstrate how the mAbs can be used in
      combination with a semiselective isolation procedure to track these opportunistic
      pathogens in environmental samples containing mixed populations of human
      pathogenic fungi. Specificity of mAb CA4 was confirmed by sequencing of the
      internally transcribed spacer 1 (ITS1)-5.8S-ITS2 rRNA-encoding regions of fungi
      isolated from estuarine muds. 

PMID- 24684243
TI  - Should academic therapeutic patents go to the highest bidder?
AB  - Universities conduct biomedical research with the self-stated goal of
      disseminating the benefits to the global public. Licensing therapeutic patents to
      the highest bidder is counterproductive to this aim, as it prioritizes income
      maximization over dissemination. We believe that licensing strategies focused on
      promoting broad access to university-discovered therapeutics better serve both
      the mission of universities and the public good. 

PMID- 24684245
TI  - Thyroid hormone supplementation in preterm infants born before 28 weeks
      gestational age and neurodevelopmental outcome at age 36 months.
AB  - BACKGROUND: Thyroid hormones are required for normal brain maturation, and
      neonatal plasma thyroid hormone concentrations are low in infants less than 28
      weeks gestation. It is not known whether treatment of such infants with thyroid
      hormone improves neurodevelopmental outcome. METHODS: At three years corrected
      age, mental, motor, and neurological development was assessed in infants born at
      less than 28 weeks gestational age who had participated in a phase 1 trial of
      differing doses and modes of administration of thyroid hormone. The trial's
      endpoints were thyroid hormone (thyroxine, T4) and thyotropin plasma
      concentrations in eight study arms: six treated with T4 [4, 8, and 16 MUg/(kg .
      day)], bolus or continuous], one treated with iodine only, and one treated with
      placebo. Follow-up at three years was not part of the original study goals.
      Developmental index scores, rates of cerebral palsy (CP), and rates of adverse
      outcome (death or moderate to severe delay in development and/or disabling CP)
      were compared between the eight study groups and between groups combined by
      dosage level, and between infants with and without T4 supplementation. RESULTS:
      Of 166 randomized infants, 32 (19%) died in the neonatal period. Of the 134
      survivors, follow-up results were available for 89 children (66%). Mental and
      motor development and rates of cerebral palsy did not differ in any of the
      comparisons made. CONCLUSION: In this study, no differences in neurodevelopment
      were found in relation to thyroid hormone treatment, but power was insufficient
      to detect any but very large differences.

PMID- 24684246
TI  - In vitro equine embryo production using air-dried spermatozoa, with different
      activation protocols and culture systems.
AB  - The aim of this work was to evaluate the use of air-dried spermatozoa for in
      vitro production of equine embryos and verify if sperm extract activation and in
      vivo culture improve in vitro embryo production. Cooled spermatozoa (control) and
      air-dried spermatozoa stored for 2, 14 or 28 days were used for ICSI sperm
      extract, or ionomycin was used for oocyte activation, and embryos were in vitro
      or in vivo (in mare's oviduct) cultured for 7 days. With in vitro culture,
      cleavage rate was higher when activating with sperm extract (P < 0.05). No
      differences in embryo development were seen between the two activation treatments
      nor between storage periods (P > 0.05). Blastocysts were obtained with cooled
      spermatozoa, and morulae were achieved using in vivo culture with 28-day storage
      spermatozoa and ionomycin-activated oocytes. When in vivo culture was performed,
      sperm DNA fragmentation was assessed using the sperm chromatin dispersion test
      and did not show statistical correlation with cleavage nor embryo recovery rates.
      In conclusion, equine embryos can be produced using air-dried spermatozoa stored
      for several weeks. Sperm extract activation increased cleavage rates but did not
      improve embryo development. In vivo culture allowed intrauterine stage embryos to
      be achieved. 

PMID- 24684244
TI  - Peripheral prion disease pathogenesis is unaltered in the absence of sialoadhesin
      (Siglec-1/CD169).
AB  - Prions are a unique group of pathogens, which are considered to comprise solely
      of an abnormally folded isoform of the cellular prion protein. The accumulation
      and replication of prions within secondary lymphoid organs is important for their
      efficient spread from the periphery to the brain where they ultimately cause
      neurodegeneration and death. Mononuclear phagocytes (MNP) play key roles in prion
      disease pathogenesis. Some MNP appear to facilitate the propagation of prions to
      and within lymphoid tissues, whereas others may aid their clearance by
      phagocytosis and by destroying them. Our recent data show that an intact splenic
      marginal zone is important for the efficient delivery of prions into the B-cell
      follicles where they subsequently replicate upon follicular dendritic cells
      before infecting the nervous system. Sialoadhesin is an MNP-restricted cell
      adhesion molecule that binds sialylated glycoproteins. Sialoadhesin is
      constitutively expressed upon splenic marginal zone metallophilic and lymph node
      sub-capsular sinus macrophage populations, where it may function to bind
      sialylated glycoproteins, pathogens and exosomes in the blood and lymph via
      recognition of terminal sialic acid residues. As the prion glycoprotein is highly
      sialylated, we tested the hypothesis that sialoadhesin may influence prion
      disease pathogenesis. We show that after peripheral exposure, prion pathogenesis
      was unaltered in sialoadhesin-deficient mice; revealing that lymphoid
      sequestration of prions is not mediated via sialoadhesin. Hence, although an
      intact marginal zone is important for the efficient uptake and delivery of prions
      into the B-cell follicles of the spleen, this is not influenced by sialoadhesin
      expression by the MNP within it. 

PMID- 24684247
TI  - Hexaphenylbenzene-based fluorescent aggregates for ratiometric detection of
      cyanide ions at nanomolar level: set-reset memorized sequential logic device.
AB  - A hexaphenylbenzene-based receptor 3 has been synthesized that forms a
      fluorescent spherical aggregate in mixed aqueous media due to its aggregation
      induced emission enhancement attributes. These fluorescent spherical aggregates
      show ratiometric response toward cyanide ions via nucleophilic addition and
      undergo deaggregation to form smaller nanoaggregates. In addition, the solution
      coated paper strips of 3 can detect cyanide ions in the range of ~2.6 ng/cm(2),
      thus, providing a simple, portable, and low-cost method for detection of cyanide
      ions in aqueous media. Receptor 3 also behaves as a set-reset memorized
      sequential logic circuit with chemical inputs of CN(-) ions and trifluoroacetic
      acid or H(+) (pH <= 3). 

PMID- 24684248
TI  - Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of
      patients with medication overuse headache after withdrawal therapy.
AB  - BACKGROUND AND PURPOSE: It is currently unknown if common genetic variants
      influence the prognosis of patients with medication overuse headache (MOH). Here
      the role of two common single nucleotide polymorphisms in the COMT gene (rs4680
      and rs6269), as well as the STin2 variable number tandem repeat (VNTR)
      polymorphism in the SLC6A4 gene, were evaluated as predictors for long-term
      outcomes of MOH patients after withdrawal therapy. METHODS: Genotyping was
      conducted by polymerase chain reaction (PCR), PCR restriction fragment length
      polymorphism analysis or real-time PCR allelic discrimination assay on genomic
      DNA extracted from peripheral blood. Gene variants association was evaluated by
      logistic regression analysis adjusted for clinical confounding factors, and the
      threshold of statistical significance for multiple testing was set at P < 0.012.
      RESULTS: Sixty-five MOH patients with unsuccessful detoxification and 83 MOH
      patients with effective drug withdrawal therapy were available for the analysis.
      rs4680G allele carriers or the COMT rs6269G-rs4680G haplotype were found to be
      associated with a lower risk of relapse within the first year after successful
      detoxification therapy, in comparison with homozygous rs4680A allele carriers
      [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05-0.61, P = 0.007] or with
      the COMT rs6269A-rs4680A haplotype (OR 0.19, 95% CI 0.06-0.54, P = 0.003),
      respectively. In addition, carriers of the STin2 VNTR short allele were found at
      higher odds for the composite poor outcome including unsuccessful withdrawal
      therapy and relapse within 12 months of follow-up after successful detoxification
      (OR 2.81, 95%CI 1.26-6.25, P = 0.009). CONCLUSIONS: Our results indicate that
      genotyping for COMT rs4680 and SLC6A4 STin2 VNTR could be useful for the
      identification of MOH patients at higher risk of poor prognosis after drug
      withdrawal.

PMID- 24684249
TI  - High-throughput cell and tissue analysis with enhanced molecular coverage by
      laser ablation electrospray ionization mass spectrometry using ion mobility
      separation.
AB  - Ambient ionization methods, such as laser ablation electrospray ionization
      (LAESI), facilitate the direct analysis of unperturbed cells and tissues in their
      native states. However, the lack of a separation step in these ionization
      techniques results in limited molecular coverage due to interferences, ion
      suppression effects, and the lack of ability to differentiate between structural
      isomers and isobaric species. In this contribution, LAESI mass spectrometry (MS)
      coupled with ion mobility separation (IMS) is utilized for the direct analysis of
      protein mixtures, megakaryoblast cell pellets, mouse brain sections, and
      Arabidopsis thaliana leaves. We demonstrate that the collision cross sections of
      ions generated by LAESI are similar to the ones obtained by ESI. In various
      applications, LAESI-IMS-MS allows for the high-throughput separation and mass
      spectrometric detection of biomolecules on the millisecond time scale with
      enhanced molecular coverage. For example, direct analysis of mouse brain tissue
      without IMS had yielded ~300 ionic species, whereas with IMS over 1 100 different
      ions were detected. Differentiating between ions of similar mass-to-charge ratios
      with dissimilar drift times in complex biological samples removes some systematic
      distortions in isotope distribution patterns and improves the fidelity of
      molecular identification. Coupling IMS with LAESI-MS also expands the dynamic
      range by increasing the signal-to-noise ratio due to the separation of isobaric
      or other interfering ionic species. We have also shown that identification of
      potential biomarkers by LAESI can be enhanced by using the drift times of
      individual ions as an additional parameter in supervised orthogonal projections
      to latent structures discriminant analysis. Comparative analysis of drift time
      versus mass-to-charge ratio plots was performed for similar tissue samples to
      pinpoint significant metabolic differences. 

PMID- 24684251
TI  - Experimental and theoretical studies of intramolecular hydrogen bonding in 3
      hydroxytetrahydropyran: beyond AIM analysis.
AB  - The conformational preferences of 3-hydroxytetrahydropyran (1) were evaluated
      using infrared and nuclear magnetic resonance spectroscopic data in solvents of
      different polarities. Theoretical calculations in the isolated phase and
      including the solvent effect were performed, showing that the most stable
      conformations for compound 1 are those containing the substituent in the axial
      and equatorial orientations. The axial conformation is more stable in the
      isolated phase and in a nonpolar solvent, while the equatorial conformation is
      more stable than the axial in polar media. The occurrence of intramolecular
      hydrogen-bonded O-H...O in the axial conformer was detected from infrared spectra
      in a nonpolar solvent at different concentrations. Our attempt to evaluate this
      interaction using population natural bond orbital and topological quantum theory
      of atoms in molecules analyses failed, but topological noncovalent interaction
      analysis was capable of characterizing it. 

PMID- 24684250
TI  - The impact of payment source and hospital type on rising cesarean section rates
      in Brazil, 1998 to 2008.
AB  - BACKGROUND: High cesarean section rates in Brazilian public hospitals and higher
      rates in private hospitals are well established. Less is known about the
      relationship between payment source and cesarean section rates within public and
      private hospitals. METHODS: We analyzed the 1998, 2003, and 2008 rounds of a
      nationally representative household survey (PNAD), which includes type of
      delivery, where it took place, and who paid for it. We construct cesarean section
      rates for various categories, and perform logistic regression to determine the
      relative importance of independent variables on cesarean section rates for all
      births and first births only. RESULTS: Brazilian cesarean section rates were 42
      percent in 1998 and 53 percent in 2008. Women who delivered publicly funded
      births in either public or private hospitals had lower cesarean section rates
      than those who delivered privately financed deliveries in public or private
      hospitals. Multivariate models suggest that older age, higher education, and
      living outside the Northeast region all positively affect the odds of delivering
      by cesarean section; effects are attenuated by the payment source-hospital type
      variable for all women and even more so among first births. CONCLUSIONS: Cesarean
      section rates have risen substantially in Brazil. It is important to distinguish
      payment source for the delivery to have a better understanding of those rates.

PMID- 24684252
TI  - Age disparities in survival from lymphoma and myeloma: a comparison between US
      and England.
AB  - Population-level survival in older patients with lymphoma is significantly lower
      than in younger patients. In this study, data were obtained from cancer
      registries in England and the United States (US) for patients diagnosed with
      Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and myeloma. Five-year relative
      survival was calculated using period analysis. Generalised linear models were
      used to determine excess hazard ratios (EHR) for older compared to younger
      patients. Five-year relative survival was lower for older patients diagnosed with
      HL, NHL and myeloma in both countries. The greatest age-related survival
      inequality was observed for patients with HL: in 2006-10 the EHR comparing
      patients aged 75 + years with those aged 15-24 years was 14.02 in the US and
      15.69 in England. For NHL, the EHR was 1.91 in the US and 3.81 in England. For
      myeloma, comparing patients aged 75 + years with those aged 25-44 years, the EHR
      was 2.79 in the US and 3.60 in England. Survival of patients with lymphoma is
      lower for older patients in both the US and England but the discrepancy is less
      in the US. Physicians should be encouraged to evaluate patients' frailty and co
      morbidities as well as their age when considering treatment options for patients
      with lymphoma and myeloma. 

PMID- 24684253
TI  - Innovative and emerging techniques in laparoscopic colorectal and hepatic
      surgery.

PMID- 24684254
TI  - Long-term cosmetic outcomes after robotic/endoscopic thyroidectomy by a gasless
      unilateral axillo-breast or axillary approach.
AB  - BACKGROUND: Although the excellent short-term cosmesis after robotic/endoscopic
      thyroidectomy has been reported, the long-term cosmetic outcome is not yet known.
      The aim of this study was to evaluate the long-term cosmetic outcome of
      robotic/endoscopic thyroidectomy. PATIENTS AND METHODS: We compared 147 patients
      who underwent robotic or endoscopic thyroidectomy using a gasless unilateral
      axillo-breast (GUAB) approach or a gasless unilateral axillary (GUA) approach
      with 161 conventional open thyroidectomy patients. Subjective cosmetic outcomes
      were evaluated using a series of scar-specific questions as well as the Vancouver
      scar scale at 12-18 months after surgery. The cosmetic satisfaction score was
      defined as the sum of the two cosmetic satisfaction questions with a rating scale
      of 1-5. The scar consciousness score was defined as the sum of the four scar
      consciousness questions with a rating scale of 0-3. RESULTS: The cosmetic
      satisfaction and scar consciousness scores were significantly better in the
      robotic/endoscopic group than in the open group (P<.001 in both). The cosmetic
      satisfaction and scar consciousness scores were the same in the robotic and
      endoscopic groups and were also the same in the GUA and GUAB approach groups.
      Patients treated by the GUA approach were more satisfied with their scarless
      breasts than patients treated by the GUAB approach having breast scars.
      CONCLUSIONS: Long-term postoperative cosmesis after robotic/endoscopic
      thyroidectomy using GUAB/GUA approaches is significantly better than conventional
      open thyroidectomy. In the robotic/endoscopic group, the scarless breasts
      resulting from the GUA approach lead to greater satisfaction than those after the
      GUAB approach.

PMID- 24684255
TI  - Use of the harmonic blade scalpel as a novel technique for thoracoscopic
      resection of pediatric paraspinal masses in children.
AB  - INTRODUCTION: Data support use of video-assisted thoracoscopic surgery (VATS) for
      safe and effective resection of paraspinal masses in children. Our aim was to
      describe outcomes following this operation using a novel technique and to compare
      its use with that of other established techniques. SUBJECTS AND METHODS: We
      performed a retrospective chart review of all children (<18 years old) undergoing
      thoracoscopic resection of paraspinal masses in 2000-2011. Demographics,
      operative details, and clinical outcomes were summarized and compared between
      those undergoing resection using a Harmonic (Ethicon Endo-Surgery, Blue Ash, OH)
      blade scalpel (HBS) and those who did not. RESULTS: Sixteen cases were identified
      (median age, 57.5 months; range, 2-204 months). Six cases (37%) underwent VATS
      with use of the HBS, and 10 (63%) did not. Demographic and clinical factors were
      well matched. Median tumor diameter was larger in the HBS group (49.2 cm(3)
      versus 18.7 cm(3); P=.07). Operative time was similar between groups (121 versus
      138 minutes; P=.25), as was the estimated blood loss (10 mL versus 30 mL; P=.91)
      and chest tube duration (2.1 versus 1.8 days; P=.78). Three cases of Horner's
      syndrome developed in the standard resection group, and one complication occurred
      in the HBS group. CONCLUSIONS: The Harmonic blade scalpel can be used as a simple
      alternative to standard dissection techniques for thoracoscopic resection of
      paraspinal masses in children.

PMID- 24684256
TI  - Smart stimuli-responsive spherical nanostructures constructed from supramolecular
      metallodendrimers via hierarchical self-assembly.
AB  - In this article, we present the design and construction of a series of
      supramolecular poly(benzyl ether) metallodendrimers featuring a well-defined
      hexagonal metallacycle at their cores via coordination-driven self-assembly. It
      was found that the second generation metallodendrimer 3c was able to
      hierarchically self-assemble into the regular vesicle-like structures. These
      nanoscale vesicles were monodisperse in shape and relatively monodisperse in size
      as detected in SEM, TEM, AFM, and DLS experiments. Notably, this kind of
      hierarchically formed vesicle-like nanostructure adopted a discrete metallacycle
      as the main skeleton, which is obviously different from many previous reports of
      nanoscale spherical architectures. Moreover, such supramolecular vesicle-like
      structures could encapsulate some fluorescent molecules, like BODIPY and SRB,
      etc. By taking advantage of the dynamic nature of metal-ligand bonds, the
      disassembly and reassembly of the hexagonal cavity core could be reversibly
      controlled by the addition and removal of bromide ions, resulting in the
      transition from the vesicles to micelles. Thus, the controlled release of
      fluorescence dye was successfully realized by the halide-induced vesicles
      micelles transition. These findings not only enrich the library of supramolecular
      metallodenrimers but also provide a new avenue to the construction of novel
      "smart" nanomaterials, which have potential application in functional molecules
      delivery and release. 

PMID- 24684257
TI  - Interspecific variations in the faecal microbiota of Procellariiform seabirds.
AB  - Despite the enormous amount of data available on the importance of gut microbiota
      in vertebrates (especially mammals), there is no information available on the
      microbiota of seabirds. Procellariiformes are long-lived seabirds that consume a
      diet high in lipids and are characterised by their ability to produce and store
      large amount of stomach oils through the partial digestion of prey (with the
      exception of the Pelecanoididae). Examining the faecal microbiota of three
      Procellariiform species (short-tailed shearwater, common diving petrel and fairy
      prion) provided a unique opportunity to not only characterise the
      gastrointestinal (GI) microbial composition of seabirds but to also examine the
      influence of stomach oils on the microbial community. The results indicated that
      Procellariiform seabirds host a highly diverse community of faecal
      microorganisms, dominated by three phyla (Firmicutes, Proteobacteria and
      Bacteroidetes) and that each species has its own species-specific GI microbiota.
      In addition, significant differences were observed in the microbial communities
      of oil-producing and non-oil-producing seabirds. This study is the first whole
      community examination and classification of the faecal microbiota of
      Procellariiform seabirds. 

PMID- 24684258
TI  - Which way is which? Examining global/local processing with symbolic cues.
AB  - A new method combining spatial-cueing and compound-stimulus paradigms draws on
      involuntary attentional orienting elicited by a spatially uninformative central
      arrow cue to investigate global/local processing under incidental processing
      conditions, wherein global/local levels were uninformative (do not aid
      performance) and task-irrelevant (need not be processed to perform the task). The
      task was peripheral target detection. Cues were compound arrows, which were
      either consistent (global/local arrows oriented in same direction) or
      inconsistent (global/local arrows oriented in opposite directions). Global/local
      processing was measured by spatial-cueing effects (response time [RT] difference
      between target locations validly cued by an arrow and targets at different
      locations), with the test of global/local advantage represented by the effect of
      cue-level for inconsistent cues (RT difference between global-valid and local
      valid cues). Cue-target interval (stimulus-onset-asynchrony [SOA]) was
      manipulated to test whether global/local advantage varied with relative stimulus
      availability. Experiment 1 observed a Cue-Level * SOA interaction such that an
      early, large global cueing effect was followed by a later, smaller local cueing
      effect, indicative of a global-to-local shift in advantage. This occurred despite
      knowledge that global/local arrows were uninformative and task-irrelevant and
      could therefore be ignored, thus displaying key properties of an involuntary
      process. Experiment 2 added neutral cues (arrow at one level, rectangle at the
      other) and determined that the reversal was not due to inhibition of the globally
      cued location or to attenuation of global information but rather to the presence
      of conflicting spatial information. Experiments 3 and 4 ruled out alternative
      accounts for these results. These data indicate global precedence in attended but
      incidentally processed objects.

PMID- 24684259
TI  - Do adults make scale errors too? How function sometimes trumps size.
AB  - Scale errors-futile attempts to use impossibly sized items as though they were
      appropriately scaled-have been thought to exist only in young children. Here, we
      document a similar version of the underlying phenomenon among adults. When asked
      to select 1 of 2 tools to achieve an instrumental goal, adults in Study 1
      frequently selected, via keypress, a tool that was "for" the goal despite the
      tool being clearly ill sized in the given instance. In doing so, adults ignored
      an alternative tool that was perfectly sized for the task. Study 2 revealed this
      outcome did not emerge from a shape bias. Study 3 confirmed findings using a
      reaching task. Results support proposals that teleofunctional (purpose-based)
      reasoning is a highly powerful influence on categorization and behavior across
      development. Toddlers' scale errors may not be a symptom of immature thinking,
      but reflect a type of reasoning apparent in mature cognition.

PMID- 24684262
TI  - Gate-tunable photoemission from graphene transistors.
AB  - In this Letter, we report gate-tunable X-ray photoelectron emission from back
      gated graphene transistors. The back-gated transistor geometry allows us to study
      photoemission from graphene layer and the dielectric substrate at various gate
      voltages. Application of gate voltage electrostatically dopes graphene and shifts
      the binding energy of photoelectrons in various ways depending on the origin and
      the generation mechanism(s) of the emitted electrons. The gate-induced shift of
      the Fermi energy of graphene alters the binding energy of the C 1s electrons,
      whereas the electric field of the gate electrodes shift the binding energy of
      core electrons emitted from the gate dielectric underneath the graphene layer.
      The gradual change of the local potential through depths of the gate dielectric
      provides quantitative electrical information about buried interfaces. Our results
      suggest that gate-tunable photoemission spectra with chemically specific
      information linked with local electrical properties opens new routes to
      elucidating operation of devices based especially on layered materials. 

PMID- 24684263
TI  - Impact of obesity on the risk of venous thromboembolism in an inpatient pediatric
      population.
AB  - INTRODUCTION: The incidence of venous thromboembolism in children has increased
      significantly over the past 20 years. Over the same period of time, there was an
      increase in the prevalence of obesity in the pediatric population. Obesity is a
      known risk factor for VTE in adults, but little information is available in
      children. METHODS: This study evaluates the relation between obesity and VTE
      using a retrospective, case-control design, comparing the body mass index (BMI)
      of patients admitted with a diagnosis of VTE versus patients admitted with other
      diagnoses, at a single institution, between 2007 and 2011. RESULTS: We studied 48
      inpatients diagnosed with deep venous thrombosis or pulmonary embolism and a
      control group of 274 age and gender matched patients admitted with other
      diagnoses. We found obese patients (BMI > 95th percentile) to have significantly
      higher risk of VTE (odds ratio 2.1, with 95% CI 1.1-4.2) than patients of normal
      weight (BMI < 85th percentile). Overweight patients (BMI 85th-95th percentile)
      did not demonstrate a significant change in risk. Most of the VTE patients were
      adolescents and the majority of them had other identifiable risk factors for
      thrombosis. CONCLUSION: This study establishes a correlation between obesity and
      VTE in a group of hospitalized children, showing a risk for VTE in obese children
      similar to the one described in much larger adult cohorts.

PMID- 24684264
TI  - Adsorption of a carboxylic acid-functionalized aminoxyl radical onto SiO2.
AB  - Silicon wafers both without and with silicon(IV) oxide surface coverage were
      covered with benzene solutions of stable organic radical 3-(N-tert-butyl-N
      aminoxyl)benzoic acid (mNBA). X-ray photoelectron spectroscopy supported the
      presence of the radical on both surface-cleaned (oxide-reduced) and oxide-covered
      surfaces. Optical waveguide spectroscopy showed that the radical retained its
      structure while adsorbed to the surface of the wafers, without noticeable
      decomposition. AFM and MFM imaging showed that the radical formed blocky
      particles with a change in rms roughness from 0.3 nm premodification to 1.7 nm
      postmodification on the surface-cleaned silicon. Similar experiments using oxide
      coated silicon showed that the radical adsorbed to form much smoother layers,
      with a small change in rms roughness from 0.2 to 0.3 nm. Contact angle
      measurements of water on the premodified and postmodified samples showed a large,
      hydrophobic change in the silicon oxide surface but only a modest change in the
      surface-cleaned silicon surface. Samples of mNBA adsorbed onto silica gel showed
      strong electron-spin resonance signals from the aminoxyl spin, even years after
      production. The results demonstrate the prospects for treating and coating oxide
      covered silicon wafers and silicon oxide-coated particles with a paramagnetically
      active organic substrate, without major chemical modification of the pretreatment
      surface; the resulting organic spin sites can be stable for years. 

PMID- 24684265
TI  - Transcriptome population genomics reveals severe bottleneck and domestication
      cost in the African rice (Oryza glaberrima).
AB  - The African cultivated rice (Oryza glaberrima) was domesticated in West Africa
      3000 years ago. Although less cultivated than the Asian rice (O. sativa), O.
      glaberrima landraces often display interesting adaptation to rustic environment
      (e.g. drought). Here, using RNA-seq technology, we were able to compare more than
      12,000 transcripts between 9 O. glaberrima, 10 wild O. barthii and one O.
      meridionalis individuals. With a synonymous nucleotide diversity pis = 0.0006 per
      site, O. glaberrima appears as the least genetically diverse crop grass ever
      documented. Using approximate Bayesian computation, we estimated that O.
      glaberrima experienced a severe bottleneck during domestication. This demographic
      scenario almost fully accounts for the pattern of genetic diversity across O.
      glaberrima genome as we detected very few outliers regions where positive
      selection may have further impacted genetic diversity. Moreover, the large excess
      of derived nonsynonymous substitution that we detected suggests that the O.
      glaberrima population suffered from the 'cost of domestication'. In addition, we
      used this genome-scale data set to demonstrate that (i) O. barthii genetic
      diversity is positively correlated with recombination rate and negatively with
      gene density, (ii) expression level is negatively correlated with evolutionary
      constraint, and (iii) one region on chromosome 5 (position 4-6 Mb) exhibits a
      clear signature of introgression with a yet unidentified Oryza species. This work
      represents the first genome-wide survey of the African rice genetic diversity and
      paves the way for further comparison between the African and the Asian rice,
      notably regarding the genetics underlying domestication traits.

PMID- 24684266
TI  - Febuxostat: drug review and update.
AB  - INTRODUCTION: Gouty arthritis and hyperuricemia have ailed humans for centuries.
      Recent advances in understanding of the mechanism(s) of their development have
      changed our perception of the disease process. Despite these gains, the treatment
      options available are limited. The FDA approval of febuxostat for the treatment
      of hyperuricemia in gout has been a significant step forward. Since its approval
      in 2009, febuxostat has proven to be safe and efficacious although concerns
      remain regarding its long-term effects and superiority to other uricosuric
      agents, such as allopurinol. AREAS COVERED: A comprehensive literature review of
      PubMed and Ovid examining clinical trials and post-marketing studies yielded
      congruent findings on efficacy and safety in elderly populations and those with
      mild-to-moderate renal/hepatic impairment. A lack of literature and clinical
      studies was found with regard to comparison of febuxostat to FDA-approved high
      dose allopurinol (> 300 mg), the safety of febuxostat in the treatment of severe
      renal/hepatic impairment and the benefit in the treatment of secondary cases of
      hyperuricemia. EXPERT OPINION: Febuxostat is effective in the treatment of mild
      to-moderate renal/hepatic impairment with dramatic effects on the serum urate
      level. It can be used safely in patients with hypersensitivity reactions to
      allopurinol. Further research is needed to determine the long-term benefits and
      risks.

PMID- 24684267
TI  - Risk of adverse events in psoriasis patients receiving classic systemic drugs and
      biologics in a 5-year observational study of clinical practice: 2008-2013 results
      of the Biobadaderm registry.
AB  - BACKGROUND: Biobadaderm is the Spanish registry of psoriasis patients receiving
      systemic treatment in clinical practice. OBJECTIVE: To compare the safety of
      biologics and classic systemic treatment. METHODS: Prospective cohort of patients
      receiving biologics and classic systemic therapies between 2008 and 2013 in 12
      hospitals are included. We registered demographic data, diagnoses, comorbidities,
      treatments and adverse events (AE). We obtained raw relative risks (RR) for
      specific AE. Multivariate analysis consisted of Cox models adjusting for age,
      gender, chronic hepatic disease and previous cancer. RESULTS: A total of 1030
      patients received biologics (2061 AE in 3681 person-years), 926 patients classic
      systemic drugs (1015 AE in 1517 person-years). Ninety-three per cent of AE in
      both groups were non-serious, 6% serious and 0.003% fatal. The age- and gender
      adjusted hazard ratio of AE was lower in the biologics group [hazard ratio 0.6
      (95% CI: 0.5-0.7)].We found no differences in rates of serious and mortal AE.
      Some system organ class AE rates differed between both groups. As limitations:
      Prescription bias might affect the incidence of AE in both groups. Association of
      drug and AE was based on timing: associations might not be causal. CONCLUSION:
      Patients receiving biologics had lower risk of AE. We did not find differences in
      the risk of serious or fatal AE.

PMID- 24684268
TI  - The evolution of seed dormancy: environmental cues, evolutionary hubs, and
      diversification of the seed plants.
AB  - Seed dormancy, by controlling the timing of germination, can strongly affect
      plant survival. The kind of seed dormancy, therefore, can influence both
      population and species-level processes such as colonization, adaptation,
      speciation, and extinction. We used a dataset comprising over 14,000 taxa in 318
      families across the seed plants to test hypotheses on the evolution of different
      kinds of seed dormancy and their association with lineage diversification. We
      found morphophysiological dormancy to be the most likely ancestral state of seed
      plants, suggesting that physiologically regulated dormancy in response to
      environmental cues was present at the origin of seed plants. Additionally, we
      found that physiological dormancy (PD), once disassociated from morphological
      dormancy, acted as an 'evolutionary hub' from which other dormancy classes
      evolved, and that it was associated with higher rates of lineage diversification
      via higher speciation rates. The environmental sensitivity provided by dormancy
      in general, and by PD in particular, appears to be a key trait in the
      diversification of seed plants.

PMID- 24684269
TI  - A single-component multidrug transporter of the major facilitator superfamily is
      part of a network that protects Escherichia coli from bile salt stress.
AB  - Resistance to high concentrations of bile salts in the human intestinal tract is
      vital for the survival of enteric bacteria such as Escherichia coli. Although the
      tripartite AcrAB-TolC efflux system plays a significant role in this resistance,
      it is purported that other efflux pumps must also be involved. We provide
      evidence from a comprehensive suite of experiments performed at two different pH
      values (7.2 and 6.0) that reflect pH conditions that E. coli may encounter in
      human gut that MdtM, a single-component multidrug resistance transporter of the
      major facilitator superfamily, functions in bile salt resistance in E. coli by
      catalysing secondary active transport of bile salts out of the cell cytoplasm.
      Furthermore, assays performed on a chromosomal DeltaacrB mutant transformed with
      multicopy plasmid encoding MdtM suggested a functional synergism between the
      single-component MdtM transporter and the tripartite AcrAB-TolC system that
      results in a multiplicative effect on resistance. Substrate binding experiments
      performed on purified MdtM demonstrated that the transporter binds to cholate and
      deoxycholate with micromolar affinity, and transport assays performed on inverted
      vesicles confirmed the capacity of MdtM to catalyse electrogenic bile salt/H(+)
      antiport.

PMID- 24684271
TI  - Mussel inspired modification of polypropylene separators by catechol/polyamine
      for Li-ion batteries.
AB  - Inspired by the remarkable adhesion of mussel, dopamine, a mimicking adhesive
      molecule, has been widely used for surface modification of various materials
      ranging from organic to inorganic. However, dopamine and its derivatives are
      expensive which impede their application in large scale. Herein, we replaced
      dopamine with low-cost catechol and polyamine (only 8% of the cost of dopamine),
      which could be polymerized in an alkaline solution and deposited on the surfaces
      of various materials. By using this cheap and simple modification method,
      polypropylene (PP) separator could be transformed from hydrophobic to
      hydrophilic, while the pore structure and mechanical property of the separator
      remained intact. The uptake of electrolyte increased from 80% to 270% after the
      hydrophilic modification. Electrochemical studies demonstrated that battery with
      the modified PP separator had a better Coulombic efficiency (80.9% to 85.3%)
      during the first cycle at a current density of 0.1 C, while the discharging
      current density increased to 15 C and the discharge capacity increased by 1.4
      times compared to the battery using the bare PP separator. Additionally, the
      modification allowed excellent stability during manifold cycles. This study
      provides new insights into utilizing low-cost chemicals to mimic the mussel
      adhesion and has potential practical application in many fields. 

PMID- 24684270
TI  - Basic quinolinonyl diketo acid derivatives as inhibitors of HIV integrase and
      their activity against RNase H function of reverse transcriptase.
AB  - A series of antiviral basic quinolinonyl diketo acid derivatives were developed
      as inhibitors of HIV-1 IN. Compounds 12d,f,i inhibited HIV-1 IN with IC50 values
      below 100 nM for strand transfer and showed a 2 order of magnitude selectivity
      over 3'-processing. These strand transfer selective inhibitors also inhibited HIV
      1 RNase H with low micromolar potencies. Molecular modeling studies based on both
      the HIV-1 IN and RNase H catalytic core domains provided new structural insights
      for the future development of these compounds as dual HIV-1 IN and RNase H
      inhibitors. 

PMID- 24684273
TI  - Differential effects and potential adverse outcomes of ionic silver and silver
      nanoparticles in vivo and in vitro.
AB  - Nanoparticles are of concern because of widespread use, but it is unclear if
      metal nanoparticles cause effects directly or indirectly. We explored whether
      polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) cause effects
      through intact nanoparticles or dissolved silver. Females of the model species
      fathead minnow (Pimephales promelas) were exposed to either 4.8 MUg/L of AgNO3 or
      61.4 MUg/L of PVP-AgNPs for 96h. Microarray analyses were used to identify
      impacted receptors and toxicity pathways in liver and brain tissues that were
      confirmed using in vitro mammalian assays. AgNO3 and PVP-AgNP exposed fish had
      common and distinct effects consistent with both intact nanoparticles and
      dissolved silver causing effects. PVP-AgNPs and AgNO3 both affected pathways
      involved in Na(+), K(+), and H(+) homeostasis and oxidative stress but different
      neurotoxicity pathways. In vivo effects were supported by PVP-AgNP activation of
      five in vitro nuclear receptor assays and inhibition of ligand binding to the
      dopamine receptor. AgNO3 inhibited ligand binding to adrenergic receptors alpha1
      and alpha2 and cannabinoid receptor CB1, but had no effect in nuclear receptor
      assays. PVP-AgNPs have the potential to cause effects both through intact
      nanoparticles and metal ions, each interacting with different initiating events.
      Since the in vitro and in vivo assays examined here are commonly used in human
      and ecological hazard screening, this work suggests that environmental health
      assessments should consider effects of intact nanoparticles in addition to
      dissolved metals. 

PMID- 24684272
TI  - Association of moyamoya disease with thyroid autoantibodies and thyroid function:
      a case-control study and meta-analysis.
AB  - BACKGROUND AND PURPOSE: Evidence suggests that elevated thyroid function and
      elevated levels of thyroid autoantibodies are associated with risk of moyamoya
      disease (MMD). Therefore a meta-analysis of all available evidence was performed,
      including unpublished data from our own center, in order to assess this
      association. METHODS: Major literature databases were reviewed without language
      restrictions to identify studies examining the association between MMD and
      thyroid function or thyroid autoantibodies. These data were combined with those
      from our own prospective study. This study involved consecutively recruited
      patients with MMD and two groups of age-matched control patients: patients with
      non-MMD stroke and healthy individuals. The groups were compared in terms of
      serum triiodothyronine (T3), thyroxine (T4), free T4, free T3, thyroid
      stimulating hormone, anti-thyroperoxidase antibody and anti-thyroglobulin
      antibody. RESULTS: Our prospective study involved 28 patients with MMD, 28 age
      matched patients with non-MMD stroke and 28 age-matched healthy control
      participants. The results showed an association between risk of MMD and elevated
      thyroid autoantibodies [odds ratio (OR) 9.00, 95% confidence interval (CI) 1.03
      78.94] but not between risk of MMD and elevated thyroid function (OR 5.87, 95% CI
      0.64-53.93). Meta-analysis of our data with findings from the literature further
      supported the association with elevated thyroid autoantibodies (OR 8.77, 95% CI
      4.45-17.29) and indicated an association with elevated thyroid function (OR 9.74,
      95% CI 2.18-43.49). CONCLUSIONS: Evidence strongly suggests that elevated thyroid
      autoantibodies and elevated thyroid function are independently associated with
      MMD. These clinical variables may require regular monitoring in patients with
      MMD.

PMID- 24684274
TI  - Beliefs about infant regulation, early infant behaviors and maternal postnatal
      depressive symptoms.
AB  - BACKGROUND: Young infants may have irregular sleeping and feeding patterns. Such
      regulation difficulties are known correlates of maternal depressive symptoms.
      Parental beliefs about their role in regulating infant behaviors also may play a
      role. We investigated the association of depressive symptoms with infant
      feeding/sleeping behaviors, parent regulation beliefs, and the interaction of the
      two. METHOD: In 2006, 272 mothers of infants aged up to 24 weeks completed a
      questionnaire about infant behavior and regulation beliefs. Participants were
      recruited from general medical practices and child health clinics in Brisbane,
      Australia. Depressive symptomology was measured using the Edinburgh Postnatal
      Depression Scale. Other measures were adapted from the ALSPAC study. RESULTS:
      Regression analyses were run controlling for partner support, other support, life
      events, and a range of demographic variables. Maternal depressive symptoms were
      associated with infant sleeping and feeding problems but not regulation beliefs.
      The most important infant predictor was sleep behaviors with feeding behaviors
      accounting for little additional variance. An interaction between regulation
      beliefs and sleep behaviors was found. Mothers with high regulation beliefs were
      more susceptible to postnatal depressive symptoms when infant sleep behaviors
      were problematic. CONCLUSION: Mothers of young infants who expect greater control
      are more susceptible to depressive symptoms when their infant presents
      challenging sleep behavior.

PMID- 24684275
TI  - Buccal bone deficiency in fresh extraction sockets: a prospective single cohort
      study.
AB  - OBJECTIVE: The purpose of this prospective single cohort study was to evaluate
      the use of xenograft and collagen membranes in treating full or partial buccal
      bone defects of fresh extraction sockets in the esthetic zone. MATERIALS AND
      METHODS: Thirty-three patients requiring tooth extraction in the anterior
      maxillary area and showing a complete or partial buccal bone plate deficiency
      (more than 2 mm) were consecutively enrolled and treated. Corticocancellous
      porcine bone and platelet-rich fibrin (PRF) with a collagen membrane were used to
      graft the extraction sockets, and the membranes were left exposed to the oral
      cavity with a secondary soft tissue healing. The outcome variables were as
      follows: width of keratinized mucosa, facial soft tissue levels, clinical bone
      changes (measured with a clinical splint), implant and prosthesis failures, and
      peri-implant marginal bone changes. RESULTS: All treated sites allowed the
      placement of implants; the width of keratinized mucosa at the mid-facial aspect
      showed an increase of 2.3 mm 5 months after the grafting procedure, and its value
      was 3.2 +/- 0.6 mm at 1-year follow-up. The mean values of the facial soft tissue
      level indicated an increase over time. The bone level showed an improvement of
      0.8 +/- 0.1 mm and 0.7 +/- 0.1 mm at mesial and distal sites, respectively, when
      compared to the baseline measurements. Finally, in the palatal area, no bone
      changes were observed. No implant failed during the entire observation period.
      CONCLUSIONS: Findings from this study showed that xenograft and PRF, used for
      ridge preservation of the extraction sockets with buccal bone plate dehiscence in
      the esthetic zone, can be considered effective in repairing bone defects before
      implant placement. The secondary soft tissue healing over the grafted sockets did
      not compromise bone formation; moreover, the soft tissue level and the width of
      keratinized gingiva showed a significant improvement over time.

PMID- 24684276
TI  - Unmasking the measles-like parchment discoloration: molecular and microanalytical
      approach.
AB  - Many ancient parchments are defaced by red or purple maculae associated with
      localized destruction of collagen fibres. Although the main characteristics of
      this damage were present in most of the manuscripts analysed by many authors, no
      common microbial or fungal denominator has been found so far, and little or no
      correspondence between the microbial or fungal species isolated from materials
      could be addressed. In this study, culture-independent molecular methods and
      scanning electron microscopy (SEM) were used to identify fungal and bacterial
      communities on parchments affected by the purple stains. Protocols for c
      extraction and nucleic-acid-based strategies were selected for assays examining
      the community structure of fungi and bacteria on biodeteriorated parchment. Both
      SEM and molecular analysis detected the presence of bacterial and fungal cells in
      the damaged areas. Halophilic, halotolerant proteolytic bacterial species were
      selected by the saline environment provided by the parchment samples. As common
      microbial denominators, members of the Actinobacteria, mainly Saccharopolyspora
      spp. and species of Aspergillus, were detected in all investigated cases. It is
      proposed that a relationship exists between the phenomenon of purple spots on
      ancient parchments and that of the 'red heat' phenomenon, known to be present in
      some products manufactured with marine salt. 

PMID- 24684277
TI  - Clinical presentation and molecular basis of congenital antithrombin deficiency
      in children: a cohort study.
AB  - In this study we report the largest descriptive cohort of congenital antithrombin
      (AT) deficiency in children, its clinical presentation, molecular basis and
      genotype-phenotype correlation. Paediatric patients diagnosed with AT deficiency
      at two tertiary care children's hospitals over a 10-year period were
      retrospectively reviewed. SERPINC1 gene sequencing was offered to subjects who
      did not already have the test performed. Molecular modelling and stability
      simulations were performed for the novel mutations identified. Twenty-nine
      subjects from 18 pedigrees were identified. Mean age (+/- standard deviation) at
      diagnosis and mean duration of follow-up were 8.4 (+/- 6.6 years and 6.6 (+/- 5.7
      years respectively. Most recent mean AT activity and AT antigen levels (n = 20)
      were 0.5 (+/- 0.0) iu/ml and 0.6 (+/- 0.1) iu/ml respectively. Ten subjects were
      diagnosed secondary to low AT activity measured following venous thrombo-embolism
      (VTE). All 10 subjects had additional risk factors at the time of VTE. None of
      the 19 subjects diagnosed with AT deficiency in the setting of positive family
      history have had VTE with 7.4 (+/- 5.8) years follow-up. Mutation analysis has
      been completed on 19 subjects from 16 pedigrees. Nine unique mutations, including
      4 novel mutations were identified.

PMID- 24684278
TI  - A case of a giant sarcomatoid basal cell carcinoma with heterologous
      osteosarcomatous elements.

PMID- 24684279
TI  - The frequency of menorrhagia and bleeding disorders in university students.
AB  - STUDY OBJECTIVE: Menorrhagia is an important health problem in women of
      reproductive age. The aims of this study were to assess the prevalence of
      menorrhagia and hemostatic abnormalities associated with menorrhagia in
      university students. METHODS: The pictorial blood assessment chart (PBAC) was
      used to identify students with menorrhagia. Those with a PBAC score > 100 were
      examined by pelvic ultrasound and laboratory tests including complete blood
      count, levels of clotting factors, von Willebrand factor antigen, and ristocetin
      cofactor activity and Platelet Function Analyser-100 (PFA-100). Platelet
      aggregation was studied in students with prolonged PFA-100 closure time. RESULTS:
      Menorrhagia was identified in 82 (21.8%) of 376 students. Six of 82 students who
      had pelvic pathologies were excluded. Eleven (14.5%) of the remaining 76 students
      were found to have bleeding disorders, including von Willebrand disease in five
      (6.5%), platelet function disorder in four (5.2%), and clotting factor
      deficiencies in two (2.6%). CONCLUSIONS: Menorrhagia is a common but mostly
      unrecognized and untreated problem among university students. Underlying bleeding
      disorders are not rare and require comprehensive hemostatic evaluation for
      identification.

PMID- 24684281
TI  - Executive functioning: developmental consequences on adolescents with histories
      of maltreatment.
AB  - Research suggests that children exposed to maltreatment have deficits in
      executive functioning (EF) but few studies have focused on the adolescent age
      group. We investigated whether maltreated adolescents had lower EF abilities
      compared to a group of non-maltreated adolescents. Forty adolescents with
      histories of child maltreatment, together with a comparison group of 40 non
      maltreated adolescents matched for age, completed a comprehensive battery of EF
      tasks. Hierarchical multiple regression analyses, controlling for IQ, were
      carried out using each of the EF measures as dependent variables to examine group
      differences. Maltreated adolescents had significantly lower performance than non
      maltreated adolescents on tasks assessing executive loaded working memory,
      fluency, and inhibition, although switching was not impaired. Emotional and
      behavioural difficulties (EBD) were included in additional regression analyses to
      examine whether these variables would explain the group differences. The
      inclusion of EBD variables had some effect on group differences, as expected, but
      did not eliminate them. These findings support the theory that impairments in EF
      may be one underlying reason why adolescents with histories of maltreatment
      struggle to cope both inside and outside the classroom. 

PMID- 24684282
TI  - Organic acid quantitation by NeuCode methylamidation.
AB  - We have developed a multiplexed quantitative analysis method for carboxylic acids
      by liquid chromatography high resolution mass spectrometry. The method employs
      neutron encoded (NeuCode) methylamine labels ((13)C or (15)N enriched) that are
      affixed to carboxylic acid functional groups to enable duplex quantitation via
      mass defect measurement. This work presents the first application of NeuCode
      quantitation to small molecules. We have applied this technique to detect
      adulteration of olive oil by quantitative analysis of fatty acid methyl amide
      derivatives, and the quantitative accuracy of the NeuCode analysis was validated
      by GC/MS. Currently, the method enables duplex quantitation and is expandable to
      at least 6-plex analysis. 

PMID- 24684283
TI  - Modification of TiO2 electrode with organic silane interposed layer for high
      performance of dye-sensitized solar cells.
AB  - Back electron transfer from the TiO2 electrode surface to the electrolyte is the
      main reason behind the low-open circuit potential (Voc) and the low-fill factor
      (FF) of the dye-sensitized solar cells (DSSCs). Modifications to the TiO2
      electrode, fabricated using {010}-faceted TiO2 nanoparticles with six different
      kinds of silane, are reported to decrease the back electron transfer on the TiO2
      surface. The effect of alkyl chain length of hydrocarbon silanes and fluorocarbon
      silanes on adsorption parameters of surface coverage and adsorption constant,
      interfacial resistance, and photovoltaic performances were investigated.
      Adsorption isotherms, impedance analysis, and photovoltaic measurements were used
      as the investigation techniques. The reduction of back electron transfer depended
      on the TiO2 surface coverage by silane, alkyl chain length, and the molecular
      structure of the silane. Even though Voc and FF were improved, significant
      reduction in short-circuit photocurrent density (Jsc) was observed after
      silanization because of desorption of dye during silanization. A new approach,
      sequential adsorption process of silane and dye, was introduced to enhance Voc
      and FF without lowering Jsc. Heptadecafluorodecyl trimethoxy-silane showed the
      highest coverage on the surface of the TiO2 and had the highest effect on the
      performance improvement of the DSSC, where Voc, FF, and efficiency (eta) were
      improved by 22, 8.0, and 22%, respectively. 

PMID- 24684280
TI  - The high mobility group A1 molecular switch: turning on cancer - can we turn it
      off?
AB  - INTRODUCTION: Emerging evidence demonstrates that the high mobility group A1
      (HMGA1) chromatin remodeling protein is a key molecular switch required by cancer
      cells for tumor progression and a poorly differentiated, stem-like state. Because
      the HMGA1 gene and proteins are expressed at high levels in all aggressive tumors
      studied to date, research is needed to determine how to 'turn off' this master
      regulatory switch in cancer. AREAS COVERED: In this review, we describe prior
      studies that underscore the central role of HMGA1 in refractory cancers and we
      discuss approaches to target HMGA1 in cancer therapy. EXPERT OPINION: Given the
      widespread overexpression of HMGA1 in diverse, aggressive tumors, further
      research to develop technology to target HMGA1 holds immense promise as potent
      anticancer therapy. Previous work in preclinical models indicates that delivery
      of short hairpin RNA or interfering RNA molecules to 'switch off' HMGA1
      expression dramatically impairs cancer cell growth and tumor progression. The
      advent of nanoparticle technology to systemically deliver DNA or RNA molecules to
      tumors brings this approach even closer to clinical applications, although
      further efforts are needed to translate these advances into therapies for cancer
      patients.

PMID- 24684284
TI  - Atomistic origins of high-performance in hybrid halide perovskite solar cells.
AB  - The performance of organometallic perovskite solar cells has rapidly surpassed
      that of both conventional dye-sensitized and organic photovoltaics. High-power
      conversion efficiency can be realized in both mesoporous and thin-film device
      architectures. We address the origin of this success in the context of the
      materials chemistry and physics of the bulk perovskite as described by electronic
      structure calculations. In addition to the basic optoelectronic properties
      essential for an efficient photovoltaic device (spectrally suitable band gap,
      high optical absorption, low carrier effective masses), the materials are
      structurally and compositionally flexible. As we show, hybrid perovskites exhibit
      spontaneous electric polarization; we also suggest ways in which this can be
      tuned through judicious choice of the organic cation. The presence of
      ferroelectric domains will result in internal junctions that may aid separation
      of photoexcited electron and hole pairs, and reduction of recombination through
      segregation of charge carriers. The combination of high dielectric constant and
      low effective mass promotes both Wannier-Mott exciton separation and effective
      ionization of donor and acceptor defects. The photoferroic effect could be
      exploited in nanostructured films to generate a higher open circuit voltage and
      may contribute to the current-voltage hysteresis observed in perovskite solar
      cells. 

PMID- 24684285
TI  - Thyroid nodules with atypia or follicular lesions of undetermined significance
      (Bethesda Category III): importance of ultrasonography and cytological
      subcategory.
AB  - BACKGROUND: One possible result of fine-needle aspiration (FNA) in patients with
      thyroid nodules is "follicular lesion of undetermined significance" (FLUS) or
      "atypia of undetermined significance" (AUS). The risk of malignancy is relevant
      information to define appropriate management, and knowledge of predictors of
      malignancy in these nodules is therefore important. The objective of this
      prospective study was to evaluate clinical, laboratory, ultrasonographic, and
      cytological predictors of malignancy in patients with thyroid nodules and
      FLUS/AUS cytology. METHODS: The sample consisted of 150 patients with thyroid
      nodules and an indication for FNA whose cytology was classified as FLUS/AUS
      according to the Bethesda classification criteria. RESULTS: In the second FNA,
      cytology was nondiagnostic in 2 (1.3%) nodules and benign in 54 (36%), FLUS/AUS
      cytology persisted in 73 (48.6%), and cytology was suspicious for follicular
      neoplasm in 11 (7.3%) and for malignancy in 10 (6.6%). The rate of malignancy was
      22.6%. Clinical and laboratory data or nodule size were not predictors of
      malignancy. The rate of malignancy was lower in nodules initially classified as
      FLUS (10.8% versus 41.3% with AUS). Ultrasonography (US) was also useful for
      predicting malignancy, with sensitivity, specificity, and positive and negative
      predictive values of 79.4%, 90.5%, 71%, and 93.75%, respectively. Different
      malignancy rates were obtained when the two parameters, cytological subcategory
      and US, were combined: (i) 3.9% for nodules nonsuspicious on US and FLUS, (ii)
      11.4% for nonsuspicious nodules with AUS, (iii) 46.6% for suspicious nodules with
      FLUS, and (iv) 87% for suspicious nodules with AUS. CONCLUSIONS: The combination
      of cytological subcategory (FLUS or AUS) and US provides different risks of
      malignancy for nodules initially classified as Bethesda category III.

PMID- 24684286
TI  - Structural and environmental features of novel mdfA variant and mdfA genes in
      recombinant regions of Escherichia coli.
AB  - Novel mdfA gene variants were identified simultaneously from 3 of 13 positive
      isolates of PCR amplification in Escherichia coli from patients. These 13
      positive isolates showed resistance to chloramphenicol, tetracycline, and
      erythromycin. The 3 mdfA gene variants were of the same genotype and all the 13
      positive isolates were investigated by conjugation experiment, EcoRI restriction,
      and gene mapping. Conjugation experiments demonstrated that the novel mdfA
      variant and mdfA genes were located on plasmids that were restricted by EcoRI for
      ~8.2 kb-length, which was also validated by gene mapping. Further study indicated
      three types of genetic structures (A, B, and C) in the recombinant plasmids
      harboring mdfA and surrounding genes, and structure B was first reported in the
      article. Structure A comprises two partial-length and six full-length genes,
      including the mdfA gene variant in the recombinant plasmid; structure B comprises
      four full-length genes, the mdfA, ybjG, dacC, and ybjI; structure C comprises two
      full-length genes, the mdfA and dacC. These results suggested that the mdfA gene
      can function as transporter responsible for multidrug resistance and also
      mediated the synergistic function with its surrounding genes in conjugative
      plasmids.

PMID- 24684287
TI  - Superparamagnetic-oil-filled nanocapsules of a ternary graft copolymer.
AB  - Stearic and oleic acid-coated Fe3O4 nanoparticles were dispersed in
      decahydronaphthalene (DN). This oil phase was dispersed in water using ternary
      graft copolymer poly(glycidyl methacrylate)-graft-[polystyrene-ran-(methoxy
      polyethylene glycol)-ran-poly(2-cinnamoyloxyethyl methacrylate)] or PGMA-g-(PS-r
      MPEG-r-PCEMA) to yield capsules. The walls of these capsules were composed of
      PCEMA chains that were soluble in neither water nor DN, and the DN-soluble PS
      chains stretched into the droplet phase and the water-soluble MPEG chains
      extended into the aqueous phase. Structurally stable capsules were prepared by
      photolyzing the capsules with UV light to cross-link the PCEMA layer. Both the
      magnetite particles and the magnetite-containing capsules were superparamagnetic.
      The sizes of the capsules increased as they were loaded with more magnetite
      nanoparticles, reaching a maximal loading of ~0.5 mg of ligated magnetite
      nanoparticles per mg of copolymer. But the radii of the capsules were always <100
      nm. Thus, a novel nanomaterial--superparamagnetic-oil-filled polymer nanocapsules
      -was prepared. The more heavily loaded capsules were readily captured by a magnet
      and could be redispersed via shaking. Although the cross-linked capsules survived
      this capturing and redispersing treatment many times, the un-cross-linked
      capsules ruptured after four cycles. These results suggest the potential to
      tailor-make capsules with tunable wall stability for magnetically controlled
      release applications.

PMID- 24684288
TI  - Herbivory and floral signaling: phenotypic plasticity and tradeoffs between
      reproduction and indirect defense.
AB  - Plant defense against herbivores may compromise attraction of mutualists, yet
      information remains limited about the mechanisms underlying such signaling
      tradeoffs. Here, we investigated the effects of foliar herbivory by two herbivore
      species on defense compounds, floral signaling, pollinator and parasitoid
      attraction, and seed production. Herbivory generally reduced the quantity of many
      floral volatile organic compounds VOCs) in Brassica rapa. By contrast, floral
      color, flower diameter, and plant height remained unaffected. The decreased
      amounts of floral volatiles led to reduced attractiveness of flowers to
      pollinators, but increased the attractiveness of herbivore-infested plants to
      parasitoids. Plants infested with the native butterfly Pieris brassicae produced
      more flowers during early flowering, effectively compensating for the lower
      olfactory attractiveness. Herbivory by the invasive Spodoptera littoralis
      increased the amounts of glucobrassicanapin, and led to delayed flowering. These
      plants tended to attract fewer pollinators and to produce fewer seeds. Our study
      indicates a tradeoff between pollinator attraction and indirect defense
      (parasitoid attraction), which can be mitigated by reduced floral VOC emission
      and production of more early flowers. We suggest that this compensatory mechanism
      is specific to plant-herbivore associations with a coevolutionary history. 

PMID- 24684289
TI  - Role of physical activity in nonalcoholic fatty liver disease in terms of
      visceral obesity and insulin resistance.
AB  - BACKGROUND & AIMS: Limited evidence supports a role for physical activity (PA) in
      nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity or/and
      insulin resistance. We investigated the association between PA and NAFLD while
      considering visceral adipose tissue (VAT) and insulin resistance in a large
      general population. METHODS: Nonalcoholic fatty liver disease was diagnosed based
      on typical ultrasonographic findings. A detailed PA questionnaire included type,
      frequency, duration and length of time that the subject engaged in PA. PA was
      determined by a metabolic equivalent. VAT was evaluated by computed tomography
      taken at the umbilicus level. RESULTS: A total of 3718 subjects were enrolled in
      the analysis. After adjusting for age, gender, body mass index, smoking,
      hypertension, diabetes, soft drink and coffee consumption, the total PA was
      inversely associated with NAFLD [4th quartile (highest activities), odds ratio
      (OR) 0.68, 95% confidence interval (CI) 0.54-0.85; 3rd quartile, OR 0.74, 95% CI
      0.59-0.93 vs. 1st quartile (lowest activities), P for trend <0.001]. After
      further adjusting for VAT or insulin resistance or both (P for trend = 0.027,
      0.001 and 0.040 respectively), this relationship was slightly attenuated but
      remained statistically significant. The leisure-time PA and weighted PA also had
      inverse associations with NAFLD independent of the VAT or insulin resistance or
      both. CONCLUSIONS: This study showed an inverse association between various types
      of PA and the prevalence of NAFLD in a dose-dependent manner that was independent
      of visceral obesity and insulin resistance. This finding suggests a beneficial
      association between PA and NAFLD.

PMID- 24684291
TI  - Cross sections for positron impact with 2,2,4-trimethylpentane.
AB  - 2,2,4-Trimethylpentane (C8H18), a hydrocarbon produced all over the world on a
      large scale in the processing of crude oil, has long been known and used in the
      energy sector. It has also recently attracted the attention of the radiation
      physics and chemistry community, owing to its applications in medical imaging
      techniques. Charged-particle interactions with this species unfortunately remain
      mostly unknown. In this study, we report on measured total cross sections for
      positron scattering from 2,2,4-trimethylpentane in the energy range from 0.12 to
      50 eV. We also present calculations of the total cross sections, elastic integral
      and differential cross sections, positronium formation cross sections, and
      inelastic integral cross sections at energies from 1 to 1000 eV using the
      independent atom model with screening corrected additivity rule. A knowledge of
      those scattering cross sections might, through simulation models, help to improve
      the accuracy of current radiation detection devices and hence provide better
      estimates of the extent of any charged-particle-induced damage in biomolecular
      systems. 

PMID- 24684290
TI  - A dual role of the transcriptional regulator TstR provides insights into cyanide
      detoxification in Lactobacillus brevis.
AB  - In this study we uncover two genes in Lactobacillus brevis ATCC 367, tstT and
      tstR, encoding for a rhodanese and a transcriptional regulator involved in
      cyanide detoxification. TstT (LVIS_0852) belongs to a new class of
      thiosulphate:cyanide sulphurtransferases. We found that TstR (LVIS_0853)
      modulates both the expression and the activity of the downstream-encoded tstT.
      The TstR binding site was identified at -1 to +33, from tstR transcriptional
      start site. EMSA revealed that sulphite, a product of the reaction catalysed by
      TstT, improved the interaction between TstR:P(tstR), while Fe(III) disrupted this
      interaction. Site-directed mutagenesis in TstR identified M64 as a key residue in
      sulphite recognition, while residues H136-H139-C167-M171 formed a pocket for
      ferric iron co-ordination. In addition to its role as a transcriptional
      repressor, TstR is also involved in regulating the thiosulphate:cyanide
      sulphurtransferase activity of TstT. A threefold increase in TstT activity was
      observed in the presence of TstR, which was enhanced by the addition of Fe(III).
      Overexpression of the tstRT operon was found to increase the cyanide tolerance of
      L. brevis and Escherichia coli. The protein-protein interaction between TstR and
      TstT described herein represents a novel mechanism for regulation of enzymatic
      activity by a transcriptional regulator.

PMID- 24684292
TI  - Accumulation of functionally immature myeloid dendritic cells in lymph nodes of
      rhesus macaques with acute pathogenic simian immunodeficiency virus infection.
AB  - Myeloid dendritic cells (mDC) are key mediators of innate and adaptive immunity
      to virus infection, but the impact of HIV infection on the mDC response,
      particularly early in acute infection, is ill-defined. We studied acute
      pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques to
      address this question. The mDC in blood and bone marrow were depleted within 12
      days of intravenous infection with SIVmac251, associated with a marked
      proliferative response. In lymph nodes, mDC were apoptotic, activated and
      proliferating, despite normal mDC numbers, reflecting a regenerative response
      that compensated for mDC loss. Blood mDC had increased expression of MHC class
      II, CCR7 and CD40, whereas in lymph nodes these markers were significantly
      decreased, indicating that acute infection induced maturation of mDC in blood but
      resulted in accumulation of immature mDC in lymph nodes. Following SIV infection,
      lymph node mDC had an increased capacity to secrete tumour necrosis factor-alpha
      upon engagement with a Toll-like receptor 7/8 ligand that mimics exposure to
      viral RNA, and this was inversely correlated with MHC class II and CCR7
      expression. Lymph node mDC had an increased ability to capture and cleave soluble
      antigen, confirming their functionally immature state. These data indicate that
      acute SIV infection results in increased mDC turnover, leading to accumulation in
      lymph nodes of immature mDC with an increased responsiveness to virus
      stimulation.

PMID- 24684294
TI  - Attrition of MSM with HIV/AIDS along the continuum of care from screening to CD4
      testing in China.
AB  - The aim of this study is to describe attrition of newly diagnosed men who have
      sex with men (MSM) living with HIV/AIDS from screening to CD4 testing and provide
      suggestions to improve HIV case management in China. Data from 15 China-Gates
      Program project cities were collected on number of MSM who underwent each step
      from HIV screening to CD4 testing. Descriptive statistics were calculated. A
      total of 76,628 HIV screening tests were performed among MSM, of which 4563 were
      HIV-positive. Most attrition occurred at confirmatory and CD4 testing. Within the
      same year, 21% (1065/4063) of MSM who screened HIV-positive did not receive
      confirmatory testing and 34% (1025/3024) of MSM newly diagnosed with HIV/AIDS did
      not receive CD4 testing. Marked differences were observed between project areas
      in attrition at these points of the care continuum. Marked differences were also
      observed across areas in the rate of CD4 counts <350 cells/mcl, ranging from 23%
      to 87%. In the current process for diagnosis and management of HIV infection in
      China, many MSM are lost to follow-up at HIV confirmation and CD4 testing.
      Actions should be taken to reduce complexity and time lag from screening to CD4
      test and emphasize the importance of remaining in care during posttest
      counseling. 

PMID- 24684293
TI  - Diacylglycerol lactones targeting the structural features that distinguish the
      atypical C1 domains of protein kinase C zeta and iota from typical C1 domains.
AB  - To explore the feasibility of developing ligands targeted to the atypical C1
      domains of protein kinase C zeta and iota, we have prepared diacylglycerol
      lactones substituted with hydrophilic groups on their side chains, which
      potentially could interact with the arginine residues that distinguish the
      atypical C1 domains of PKCzeta and PKCiota from typical C1 domains, and we have
      measured their binding to mutated versions of the C1b domain of PKCdelta that
      incorporate one or more of these arginine residues. The most selective of the
      diacylglycerol lactones showed only a 10-fold reduction in binding affinity with
      the triple arginine mutant (N7R/S10R/L20R) compared to the wild-type, whereas
      phorbol 12,13-dibutyrate showed a 6000-fold loss of affinity. Molecular modeling
      confirms that these ligands are indeed able to interact with the arginine
      residues. Our results show that dramatic changes in selectivity can be obtained
      through appropriate substitution of diacylglycerol lactones. 

PMID- 24684295
TI  - Association between G6PD deficiency and hyperbilirubinemia in neonates: a meta
      analysis.
AB  - Hyperbilirubinemia is prevalent in newborns and multiple factors are responsible
      for the occurrence of neonatal hyperbilirubinemia. G6PD (Glucose-6-Phosphate
      Dehydrogenase) deficiency is recognized as one of the risk factors. However, many
      pediatricians did not take into account the probable effect of G6PD-deficiency
      when severe neonatal hyperbilirubinemia occurred. The aim of the present study
      was to perform a meta-analysis to investigate whether G6PD-deficiency increases
      the risk of hyperbilirubinemia and phototherapy in newborn. We searched PubMed
      and Embase databases for eligible articles according to explicit study inclusion
      and exclusion criteria. Risk ratios (RRs) and 95% confidence interval (CI) were
      selected as the evaluation indexes. Cochrane Q and I(2) test were utilized to
      assess the heterogeneity among studies. A total of five cohort studies were
      included in this meta-analysis. There were 21,585 participants enrolled in these
      studies including 877 newborns with hyperbilirubinemia and 261 newborns receiving
      phototherapy. Comparison of the incidence of hyperbilirubinemia in newborns with
      G6PD-deficiency to the ones with normal G6PD in each study yielded a pooled RR of
      3.92 (95% CI, 2.13-7.20; P <.0001). The pooled RR of receiving phototherapy in
      G6PD-deficiency neonates is 3.01 (95% CI, 2.20-4.12; P <.0001) when compared to
      G6PD normal neonates. This study revealed a significant correlation between G6PD
      deficiency and neonatal hyperbilirubinemia, as well as G6PD-deficiency and
      phototherapy. G6PD-deficient newborns have higher risk of hyperbilirubinemia and
      phototherapy than the ones with normal G6PD. Monitoring the level of G6PD in
      newborns is important for predicting the occurrence of hyperbilirubinemia.

PMID- 24684296
TI  - The science of dermocosmetics and its role in dermatology.
AB  - Our increased knowledge of normal skin physiology has ushered in a subtle
      revolution in cosmetic science. Originally designed as preparations to enhance
      personal appearance by direct application on to the skin, cosmetics have now
      taken on a new role in dermatology, through the support of the management of many
      skin disorders. This evolving role of cosmetics in skin care is primarily due to
      scientific and technological advancements that have changed our understanding of
      normal skin physiology and how cosmetics modify its appearance both physically
      and biologically. The vast array of techniques currently available to investigate
      skin responsivity to multiple stimuli has brought about a new era in cosmetic and
      dermocosmetic development based on a robust understanding of skin physiology and
      its varied responses to commonly encountered environmental insults. Most cosmetic
      research is undertaken on reconstructed skin models crucial in dermatological
      research, given the strict ban imposed by the European Union on animal testing.
      In addition, the design and conduct of trials evaluating cosmetics now follow
      rules comparable to those used in the development and evaluation of
      pharmaceutical products. Cosmetic research should now aim to ensure all trials
      adhere to strictly reproducible and scientifically sound methodologies. The
      objective of this review is to provide an overview of the multidisciplinary
      scientific approach used in formulating dermocosmetics, and to examine the major
      advances in dermocosmetic development and assessment, the safety and regulatory
      guidelines governing their production and the exciting future outlook for these
      dermocosmetic processes following good practice rules. 

PMID- 24684297
TI  - Effects of batroxobin with continuous transcranial Doppler monitoring in patients
      with acute cerebral stroke: a randomized controlled trial.
AB  - Our objective was to determine whether continuous transcranial Doppler (TCD)
      monitoring could safely enhance the efficacy of batroxobin, a thrombin-like
      enzyme extracted from Bothrops atrox moojeni venom, in the treatment for acute
      cerebral stroke beyond the thrombolytic time window. Ninety patients suffering an
      acute cerebral stroke were recruited into the study within 12 hours after the
      onset of symptoms. Patients were randomized to receive batroxobin with (target
      group) or without 1 hour of continuous TCD monitoring (control group). Clinical
      evaluation of stroke was based on the National Institutes of Health Stroke Scale
      (NIHSS) score, Barthel index (BI), Thrombolysis in Brain Ischemia score (TIBI),
      the incidence of advancing stroke, and the recurrence of cerebral infarction. The
      patients receiving continuous TCD monitoring showed significant improvement in
      NIHSS score at 57 days post treatment compared with the control. Similarly,
      patients receiving continuous TCD monitoring also showed significant improvement
      in BI at 3 months compared with the controls. Consistently, both the incidence of
      advancing stroke after 1 week and the incidence of stroke recurrence after 3
      months were significantly lower in TCD monitored group than control group.
      Moreover, the safety of the employment of TCD monitoring in the treatment of
      these patients was confirmed as there was no significant difference of the
      incidence of intracranial hemorrhage at 1 week after the treatment between the
      target and control groups. Taken together, our study showed that batroxobin, in
      combination with continuous TCD monitoring at the middle cerebral artery, reduced
      the incidence of advancing stroke and stroke recurrence after treatment without
      adverse effects in terms of poststroke intracranial hemorrhage.

PMID- 24684298
TI  - Drivers shaping the diversity and biogeography of total and active bacterial
      communities in the South China Sea.
AB  - To test the hypothesis that different drivers shape the diversity and
      biogeography of the total and active bacterial community, we examined the
      bacterial community composition along two transects, one from the inner Pearl
      River estuary to the open waters of the South China Sea (SCS) and the other from
      the Luzon Strait to the SCS basin, using 454 pyrosequencing of the 16S rRNA and
      16S rRNA gene (V1-3 regions) and thereby characterizing the active and total
      bacterial community, respectively. The diversity and biogeographic patterns
      differed substantially between the active and total bacterial communities.
      Although the composition of both the total and active bacterial community was
      strongly correlated with environmental factors and weakly correlated with
      geographic distance, the active bacterial community displayed higher
      environmental sensitivity than the total community and particularly a greater
      distance effect largely caused by the active assemblage from deep waters. The 16S
      rRNA vs. rDNA relationships indicated that the active bacteria were low in
      relative abundance in the SCS. This might be due to a high competition between
      active bacterial taxa as indicated by our community network models. Based on
      these analyses, we speculate that high competition could cause some dispersal
      limitation of the active bacterial community resulting in a distinct distance
      decay relationship. Altogether, our results indicated that the biogeographic
      distribution of bacteria in the SCS is the result of both environmental control
      and distance decay. 

PMID- 24684299
TI  - Muscle atrophy in chronic inflammatory demyelinating polyneuropathy: a computed
      tomography assessment.
AB  - BACKGROUND AND PURPOSE: Muscle atrophy is generally mild in patients with chronic
      inflammatory demyelinating polyneuropathy (CIDP) compared with the severity and
      duration of the muscle weakness. Muscle atrophy was evaluated using computed
      tomography (CT) in patients with CIDP. METHODS: Thirty-one patients with typical
      CIDP who satisfied the diagnostic criteria for the definite CIDP classification
      proposed by the European Federation of Neurological Societies and the Peripheral
      Nerve Society were assessed. The clinicopathological findings in patients with
      muscle atrophy were also compared with those in patients without atrophy.
      RESULTS: Computed tomography evidence was found of marked muscle atrophy with
      findings suggestive of fatty degeneration in 11 of the 31 patients with CIDP. CT
      assessed muscle atrophy was in the lower extremities, particularly in the ankle
      plantarflexor muscles. Muscle weakness, which reflects the presence of muscle
      atrophy, tended to be more pronounced in the lower extremities than in the upper
      extremities in patients with muscle atrophy, whereas the upper and lower limbs
      tended to be equally affected in patients without muscle atrophy. Nerve
      conduction examinations revealed significantly greater reductions in compound
      muscle action potential amplitudes in the tibial nerves of patients with muscle
      atrophy. Sural nerve biopsy findings were similar in both groups. The functional
      prognoses after immunomodulatory therapies were significantly poorer amongst
      patients with muscle atrophy. CONCLUSIONS: Muscle atrophy was present in a
      subgroup of patients with CIDP, including patients with a typical form of the
      disease. These patients tended to demonstrate predominant motor impairments of
      the lower extremities and poorer functional prognoses.

PMID- 24684300
TI  - Repetitive hypoglycemia increases circulating adrenaline level with resultant
      worsening of intimal thickening after vascular injury in male Goto-Kakizaki rat
      carotid artery.
AB  - Hypoglycemia associated with diabetes management is a potential risk for
      cardiovascular diseases. However, the effect of hypoglycemic episodes including a
      surge of sympathetic activity on the progression of neointima formation after
      vascular injury remains largely unknown. In this study, insulin was injected
      intraperitoneally into nonobese diabetic Goto-Kakizaki (GK) rats, once every 3
      days for 4 weeks after balloon injury of carotid artery to induce hypoglycemia.
      Then, we evaluated balloon injury-induced neointima formation. Insulin treatment
      enhanced neointima formation and increased the number of proliferating cell
      nuclear antigen (PCNA)-positive cells in the carotid artery. Injection of glucose
      with insulin prevented hypoglycemia and abrogated intimal thickening. Also,
      bunazosin, an alpha1 adrenergic receptor antagonist, prevented intimal thickening
      and accumulation of PCNA-positive cells induced by insulin treatment despite the
      presence of concomitant hypoglycemia and high adrenaline levels. Incubation of
      cultured smooth muscle cells with adrenaline resulted in a significant increase
      in their proliferation and G0/G1 to S phase progression, which was associated
      with activation of extracellular signal-regulated kinase, enhanced expression of
      cell cycle regulatory molecules such as cyclin D1, and cyclin E, and
      phosphorylation of retinoblastoma protein. These adrenaline-induced effects were
      abrogated by bunazosin. Our data indicated that increased adrenaline induced by
      repetitive hypoglycemia promotes intimal thickening and smooth muscle cell
      proliferation after endothelial denudation in GK rats. 

PMID- 24684302
TI  - Deficiency of clusterin exacerbates high-fat diet-induced insulin resistance in
      male mice.
AB  - The present study examined the role of clusterin in insulin resistance in high
      fat-fed wild-type and clusterin knockout (KO) mice. The plasma levels of glucose
      and C-peptide and islet size were increased in clusterin KO mice after an 8-week
      high-fat diet. In an ip glucose tolerance test, the area under the curve for
      glucose was not different, whereas the area under the curve for insulin was
      higher in clusterin KO mice. In a hyperinsulinemic-euglycemic clamp, the clamp
      insulin levels were higher in clusterin KO mice after the high-fat diet. After
      adjusting for the clamp insulin levels, the glucose infusion rate, suppression of
      hepatic glucose production, and glucose uptake were lower in clusterin KO mice in
      the high fat-fed group. The plasma levels of clusterin and clusterin mRNA levels
      in the skeletal muscle and liver were increased by the high-fat diet. The mRNA
      levels of the antioxidant enzymes were lower, and the mRNA levels of nicotinamide
      adenine dinucleotide phosphate oxidase (NOX) 1 and cytokines and protein
      carbonylation were higher in the skeletal muscle and liver in clusterin KO mice
      after the high-fat diet. Palmitate-induced gene expressions of NOX1 and cytokines
      were higher in the primary cultured hepatocytes of clusterin KO mice compared
      with the wild-type mice. Clusterin inhibited the gene expression and reactive
      oxygen species generation by palmitate in the hepatocytes and C2C12. AKT
      phosphorylation by insulin was reduced in the hepatocytes of clusterin KO mice.
      These results suggest that clusterin plays a protective role against high-fat
      diet-induced insulin resistance through the suppression of oxidative stress and
      inflammation. 

PMID- 24684301
TI  - Activation of cAMP signaling attenuates impaired hepatic glucose disposal in aged
      male p21-activated protein kinase-1 knockout mice.
AB  - p21-activated protein kinase-1 (Pak1) plays a role in insulin secretion and
      glucagon-like peptide-1 (GLP-1) production. Pak1(-/-) mice were found to carry a
      defect in ip pyruvate tolerance test (IPPTT), leading us to speculate whether
      Pak1 represses hepatic gluconeogenesis. We show here that the defect in IPPTT
      became more severe in aged Pak1(-/-) mice. In primary hepatocytes, 2,2'-dihydroxy
      1,1'-dinaphthyldisulfide, a potent inhibitor of group I Paks, reduced basal
      glucose production (GP), attenuated forskolin- or glucagon-stimulated GP, and
      attenuated the stimulation of forskolin on the expression of Pck1 and G6pc. In
      addition, the capacity of primary hepatocytes isolated from Pak1(-/-) mice in GP
      at the basal level is significantly lower than that of the control littermates.
      These in vitro observations imply that the direct effect of Paks in hepatocytes
      is the stimulation of gluconeogenesis and that the impairment in IPPTT in Pak1(-/
      ) mice is due to the lack of Pak1 elsewhere. Consecutive ip injection of
      forskolin for 2 weeks increased gut proglucagon expression, associated with
      improved IPPTT in aged Pak1(-/-) mice and wild-type controls. In addition,
      administration of the DPP-IV (dipeptidyl peptidase-4) inhibitor sitagliptin for 1
      week reversed the defect in IPPTT in aged Pak1(-/-) mice, associated with
      increased plasma GLP-1 levels. Our observations indicate a potential role of Pak1
      in the gut/pancreas/liver axis in controlling glucose disposal and affirmed the
      therapeutic application of GLP-1 and DPP-IV inhibitors in attenuating hepatic
      gluconeogenesis. 

PMID- 24684303
TI  - Adiponectin suppresses angiotensin II-induced inflammation and cardiac fibrosis
      through activation of macrophage autophagy.
AB  - Previous studies have indicated that adiponectin (APN) protects against cardiac
      remodeling, but the underlying mechanism remains unclear. The present study aimed
      to elucidate how APN regulates inflammatory responses and cardiac fibrosis in
      response to angiotensin II (Ang II). Male APN knockout (APN KO) mice and wild
      type (WT) C57BL/6 littermates were sc infused with Ang II at 750 ng/kg per
      minute. Seven days after Ang II infusion, both APN KO and WT mice developed
      equally high blood pressure levels. However, APN KO mice developed more severe
      cardiac fibrosis and inflammation compared with WT mice. This finding was
      demonstrated by the up-regulation of collagen I, alpha-smooth muscle actin, IL
      1beta, and TNF-alpha and increased macrophage infiltration in APN KO mice.
      Moreover, there were substantially fewer microtubule-associated protein 1 light
      chain 3-positive autophagosomes in macrophages in the hearts of Ang II-infused
      APN KO mice. Additional in vitro studies also revealed that globular APN
      treatment induced autophagy, inhibited Ang II-induced nuclear factor-kappaB
      activity, and enhanced the expression of antiinflammatory cytokines, including IL
      10, macrophage galactose N-acetyl-galactosamine specific lectin 2, found in
      inflammatory zone 1, and type-1 arginase in macrophages. In contrast, APN-induced
      autophagy and antiinflammatory cytokine expression was diminished in Atg5
      knockdown macrophages or by Compound C, an inhibitor of adenosine 5'
      monophosphate-activated protein kinase. Our study indicates that APN activates
      macrophage autophagy through the adenosine 5'-monophosphate-activated protein
      kinase pathway and suppresses Ang II-induced inflammatory responses, thereby
      reducing the extent of cardiac fibrosis. 

PMID- 24684304
TI  - Use of a mouse in vitro fertilization model to understand the developmental
      origins of health and disease hypothesis.
AB  - The Developmental Origins of Health and Disease hypothesis holds that alterations
      to homeostasis during critical periods of development can predispose individuals
      to adult-onset chronic diseases such as diabetes and metabolic syndrome. It
      remains controversial whether preimplantation embryo manipulation, clinically
      used to treat patients with infertility, disturbs homeostasis and affects long
      term growth and metabolism. To address this controversy, we have assessed the
      effects of in vitro fertilization (IVF) on postnatal physiology in mice. We
      demonstrate that IVF and embryo culture, even under conditions considered optimal
      for mouse embryo culture, alter postnatal growth trajectory, fat accumulation,
      and glucose metabolism in adult mice. Unbiased metabolic profiling in serum and
      microarray analysis of pancreatic islets and insulin sensitive tissues (liver,
      skeletal muscle, and adipose tissue) revealed broad changes in metabolic
      homeostasis, characterized by systemic oxidative stress and mitochondrial
      dysfunction. Adopting a candidate approach, we identify thioredoxin-interacting
      protein (TXNIP), a key molecule involved in integrating cellular nutritional and
      oxidative states with metabolic response, as a marker for preimplantation stress
      and demonstrate tissue-specific epigenetic and transcriptional TXNIP
      misregulation in selected adult tissues. Importantly, dysregulation of TXNIP
      expression is associated with enrichment for H4 acetylation at the Txnip promoter
      that persists from the blastocyst stage through adulthood in adipose tissue. Our
      data support the vulnerability of preimplantation embryos to environmental
      disturbance and demonstrate that conception by IVF can reprogram metabolic
      homeostasis through metabolic, transcriptional, and epigenetic mechanisms with
      lasting effects for adult growth and fitness. This study has wide clinical
      relevance and underscores the importance of continued follow-up of IVF-conceived
      offspring. 

PMID- 24684305
TI  - Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and
      physiological responses to maternal high-fat diet feeding.
AB  - A wealth of animal and human studies demonstrate that early life environment
      significantly influences adult metabolic balance, however the etiology for
      offspring metabolic misprogramming remains incompletely understood. Here, we
      determine the effect of maternal diet per se on offspring sex-specific outcomes
      in metabolic health and hypothalamic transcriptome regulation in mice.
      Furthermore, to define developmental periods of maternal diet misprogramming
      aspects of offspring metabolic balance, we investigated offspring physiological
      and transcriptomic consequences of maternal high-fat/high-sugar diet feeding
      during pregnancy and/or lactation. We demonstrate that female offspring of high
      fat/high-sugar diet-fed dams are particularly vulnerable to metabolic
      perturbation with body weight increases due to postnatal processes, whereas in
      utero effects of the diet ultimately lead to glucose homeostasis dysregulation.
      Furthermore, glucose- and maternal-diet sensitive gene expression modulation in
      the paraventricular hypothalamus is strikingly sexually dimorphic. In summary, we
      uncover female-specific, maternal diet-mediated in utero misprogramming of
      offspring glucose homeostasis and a striking sexual dimorphism in glucose- and
      maternal diet-sensitive paraventricular hypothalamus gene expression adjustment.
      Notably, female offspring metabolic vulnerability to maternal high-fat/high-sugar
      diet propagates a vicious cycle of obesity and type 2 diabetes in subsequent
      generations. 

PMID- 24684306
TI  - Evaluation of sodium benzoate and licorice (Glycyrrhiza glabra) root extract as
      heat-sensitizing additives against Escherichia coli O157:H7 in mildly heated
      young coconut liquid endosperm.
AB  - This study evaluated the use of sodium benzoate (SB) and licorice root extract
      (LRE) as heat-sensitizing additives against Escherichia coli O157:H7 in mildly
      heated young coconut liquid endosperm. Consumer acceptance scoring showed that
      maximum permissible supplementation (MPS) levels for SB and LRE were at 300 and
      250 ppm, respectively. The MPS values were considered in the generation of a 2
      factor rotatable central composite design for the tested SB and LRE concentration
      combinations. Liquid endosperm with various SB and LRE supplementation
      combinations was inoculated with E. coli O157:H7 and heated to 55 degrees C. The
      susceptibility of the cells towards heating was expressed in terms of the decimal
      reduction time (D55 ). Response surface analysis showed that only the individual
      linear effect of benzoate significantly influenced D55 value, where increasing
      supplementation level resulted in increasing susceptibility. The results reported
      could serve as baseline information in further investigating other additives that
      could be used as heat-sensitizing agents against pathogens in heat-labile food
      systems. SIGNIFICANCE AND IMPACT OF THE STUDY: Fruit juice products have been
      linked to outbreaks of microbial infection, where unpasteurized products were
      proven vectors of diseases. Processors often opt not to apply heat process to
      juice products as the preservation technique often compromises the sensorial
      quality. This work evaluated two common additives for their heat-sensitizing
      effects against E. coli O157:H7 in coconut liquid endosperm, the results of which
      may serve as baseline information to small- and medium-scale processors, and
      researchers in the establishment of mild heat process schedule for the test
      commodity and other similar products.

PMID- 24684307
TI  - The chequered history of the antiphospholipid syndrome.
AB  - Consideration of the chronology of advances in medical knowledge can provide
      useful insights into the pathogenesis, diagnosis and treatment of diseases. The
      antiphospholipid syndrome is an enigmatic disorder and this is reinforced by the
      misleading associated terminology, the adoption of which results directly from
      early discoveries relating to the condition. Thus the target antigen of the
      causative autoantibodies in antiphospholipid syndrome does not reside on
      phospholipid, and the frequently associated lupus anticoagulant is not restricted
      to subjects with systemic lupus erythematosus and, paradoxically, despite causing
      prolongation of clotting times in vitro it is associated with a pronounced
      tendency to thrombosis. Recognition of the antiphospholipid syndrome has its
      origins in the identification of subjects with so-called biological false
      positive serological reactions for syphilis in the middle years of the last
      century. Since that time there have been considerable advances in our
      understanding of the pathogenesis of the disease and the clinical manifestations
      and associations, improved diagnostic accuracy and an evolving evidence base for
      optimal therapy. However many gaps in our knowledge remain. 

PMID- 24684308
TI  - Human-impacted areas of France are environmental reservoirs of the
      Pseudallescheria boydii/Scedosporium apiospermum species complex.
AB  - Species of the Pseudallescheria boydii/Scedosporium apiospermum complex (PSC) are
      emerging fungal pathogens able to chronically colonize the airways of patients
      with cystic fibrosis (CF). As P. boydii was found more frequently colonizing the
      lungs of CF patients in France than in other European countries in a previous
      report, the present study was conducted in order to clarify distribution of PSC
      species in France and to characterize their natural habitat. The highest
      densities of PSC isolates were found in human-impacted areas, i.e. agricultural
      areas, fluids obtained from wastewater treatment plants, playgrounds and
      industrial areas. PSC was not detected from soil samples collected in forests.
      Most PSC culture-positive soil samples exhibited a pH range of 6-8. Scedosporium
      dehoogii, the most abundant species, was detected in all human-impacted area
      types except vineyards, whereas Scedosporium aurantiacum was mostly found in
      agricultural areas. Pseudallescheria boydii and S. apiospermum were predominantly
      isolated from seashores and playgrounds respectively. Pseudallescheria
      minutispora was found only once from a playground. This study highlights
      potential sources of contamination of the patients, especially in the CF context.

PMID- 24684309
TI  - Influence of collar design on peri-implant tissue healing around immediate
      implants: A pilot study in Foxhound dogs.
AB  - PURPOSE: The study aims to assess the soft tissue level (STL) and crestal bone
      level (CBL), of titanium dental implants with different mixed collar abutments
      configurations. MATERIALS AND METHODS: This study included 48 implants with the
      same dimensions. They were divided into two groups of 24 implants each one:
      implants with a polished collar of 2 mm plus a roughened area of 0.8 mm (CONTROL)
      and implants with a polished collar of 0.8 mm plus a micro-threated and roughened
      area of 2 mm (TEST). The implants were inserted randomly in the post-extraction
      sockets of P2, P3, P4, and M1 bilaterally in the lower jaw of six foxhound dogs.
      STL and CBL were evaluated after 8 and 12 weeks by histology and histometry.
      RESULTS: All implants were clinically and histologically osseointegrated. Healing
      patterns examined microscopically at 8 and 12 weeks for both groups yielded
      similar qualitative findings for the STL evaluation, without significant
      differences between groups (P > 0.05). CBL was significantly higher in the buccal
      side in comparison with the lingual side for both groups (P < 0.05); the
      comparison between groups at 8 weeks showed IS-B (distance from the implant
      shoulder to the top of the bony crest) and IS-C (distance from the implant
      shoulder to the first bone-to-implant contact) values significantly higher for
      control group in comparison with test (P < 0.05). At 12 weeks, CBL showed
      increased values for both groups that were higher in controls group in comparison
      with test (P < 0.05). CONCLUSIONS: Bony crest resorption could not be avoided
      both at test and control sites. However, the neck conformation at the test sites
      reduced the buccal bone resorption. Soft tissue dimensions were similar both at
      the test and control sites.

PMID- 24684310
TI  - Proteomic identification of monoclonal antibodies from serum.
AB  - Characterizing the in vivo dynamics of the polyclonal antibody repertoire in
      serum, such as that which might arise in response to stimulation with an antigen,
      is difficult due to the presence of many highly similar immunoglobulin proteins,
      each specified by distinct B lymphocytes. These challenges have precluded the use
      of conventional mass spectrometry for antibody identification based on peptide
      mass spectral matches to a genomic reference database. Recently, progress has
      been made using bottom-up analysis of serum antibodies by nanoflow liquid
      chromatography/high-resolution tandem mass spectrometry combined with a sample
      specific antibody sequence database generated by high-throughput sequencing of
      individual B cell immunoglobulin variable domains (V genes). Here, we describe
      how intrinsic features of antibody primary structure, most notably the
      interspersed segments of variable and conserved amino acid sequences, generate
      recurring patterns in the corresponding peptide mass spectra of V gene peptides,
      greatly complicating the assignment of correct sequences to mass spectral data.
      We show that the standard method of decoy-based error modeling fails to account
      for the error introduced by these highly similar sequences, leading to a
      significant underestimation of the false discovery rate. Because of these
      effects, antibody-derived peptide mass spectra require increased stringency in
      their interpretation. The use of filters based on the mean precursor ion mass
      accuracy of peptide-spectrum matches is shown to be particularly effective in
      distinguishing between "true" and "false" identifications. These findings
      highlight important caveats associated with the use of standard database search
      and error-modeling methods with nonstandard data sets and custom sequence
      databases. 

PMID- 24684311
TI  - Photoanode current of large-area MoS2 ultrathin nanosheets with vertically mesh
      shaped structure on indium tin oxide.
AB  - A large area of hydrothermally grown MoS2 ultrathin nanosheets (NSs) with a
      vertically mesh-shaped structure on indium tin oxide (ITO) substrate was directly
      used as the photoanode of a potoelectrochemical (PEC) cell. The
      photoelectrocatalytic capacity of ultrathin MoS2 NSs was demonstrated, which was
      attributed not only to the excellent electrocatalytic activity originating from
      the exposed preferentially active edge sites but also to the superior
      photoelectric response resulting from the large light absorption of ultrathin
      MoS2 NSs and from the efficient separation of electron-hole pairs at the ITO/MoS2
      interfaces. The significantly enhanced photocurrent indicates that the MoS2
      ultrathin NSs can be a promising photoelectrocatalyst for PEC cells, unveiling
      the potential of MoS2-based PEC cells for solar energy absorption and conversion.

PMID- 24684312
TI  - Intradermal glutamate and capsaicin injections: intra- and interindividual
      variability of provoked hyperalgesia and allodynia.
AB  - Intradermal injections of glutamate and capsaicin are attractive to use in human
      experimental pain models because hyperalgesia and allodynia mimic isolated
      aspects of clinical pain disorders. The aim of the present study was to
      investigate the reproducibility of these models. Twenty healthy male volunteers
      (mean age 24 years; range 18-38 years) received intradermal injections of
      glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick
      hyperalgesia and brush-evoked allodynia were investigated using von Frey
      filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary
      hyperalgesia and allodynia were quantified immediately after injection and after
      15, 30 and 60 min. Two identical experiments separated by at least 7 days were
      performed. Reproducibility across and within volunteers (inter- and intra
      individual variation, respectively) was assessed using intraclass correlation
      coefficient (ICC) and coefficient of variation (CV). Secondary pinprick
      hyperalgesia was observed as a marked increase in the visual analogue scale (VAS)
      response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection.
      For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey
      gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey
      gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was
      reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71).
      Intra-individual variability was generally lower for the VAS response to von Frey
      and brush compared with areas of secondary hyperalgesia and allodynia. In
      conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic
      responses, and the present model is well suited for basic research, as well as
      for assessing the modulation of central phenomena. 

PMID- 24684313
TI  - Exohedral physisorption of ambient moisture scales non-monotonically with fiber
      proximity in aligned carbon nanotube arrays.
AB  - Here we present a study on the presence of physisorbed water on the surface of
      aligned carbon nanotubes (CNTs) in ambient conditions, where the wet CNT array
      mass can be more than 200% larger than that of dry CNTs, and modeling indicates
      that a water layer >5 nm thick can be present on the outer CNT surface. The
      experimentally observed nonlinear and non-monotonic dependence of the mass of
      adsorbed water on the CNT packing (volume fraction) originates from two competing
      modes. Physisorbed water cannot be neglected in the design and fabrication of
      materials and devices using nanowires/nanofibers, especially CNTs, and further
      experimental and ab initio studies on the influence of defects on the surface
      energies of CNTs, and nanowires/nanofibers in general, are necessary to
      understand the underlying physics and chemistry that govern this system. 

PMID- 24684315
TI  - Individual differences in adaptive coding of face identity are linked to
      individual differences in face recognition ability.
AB  - Despite their similarity as visual patterns, we can discriminate and recognize
      many thousands of faces. This expertise has been linked to 2 coding mechanisms:
      holistic integration of information across the face and adaptive coding of face
      identity using norms tuned by experience. Recently, individual differences in
      face recognition ability have been discovered and linked to differences in
      holistic coding. Here we show that they are also linked to individual differences
      in adaptive coding of face identity, measured using face identity aftereffects.
      Identity aftereffects correlated significantly with several measures of face
      selective recognition ability. They also correlated marginally with own-race face
      recognition ability, suggesting a role for adaptive coding in the well-known
      other-race effect. More generally, these results highlight the important
      functional role of adaptive face-coding mechanisms in face expertise, taking us
      beyond the traditional focus on holistic coding mechanisms.

PMID- 24684314
TI  - Characterization of mechanics and cytocompatibility of fibrin-genipin annulus
      fibrosus sealant with the addition of cell adhesion molecules.
AB  - There is an unmet clinical need for a biomaterial sealant capable of repairing
      small annulus fibrosus (AF) defects. Causes of these defects include painful
      intervertebral disc herniations, microdiscectomy procedures, morbidity associated
      with needle puncture injury from discography, and future nucleus replacement
      procedures. This study describes the enhancements of a fibrin gel through genipin
      crosslinking (FibGen) and the addition of the cell adhesion molecules (CAMs),
      fibronectin and collagen. The gel's performance as a potential AF sealant is
      assessed using a series of in vitro tests. FibGen gels with CAMs had equivalent
      adhesive strength, gene expression, cytomorphology, and cell proliferation as
      fibrin alone. However, FibGen gels had enhanced material behaviors that were
      tunable to higher shear stiffness values and approximated human annulus tissue as
      compared with fibrin alone, were more dimensionally stable, and had a slower in
      vitro degradation rate. Cytomorphology of human AF cells cultured on FibGen gels
      exhibited increased elongation compared with fibrin alone, and the addition of
      CAMs to FibGen did not significantly affect elongation. This FibGen gel offers
      the promise of being used as a sealant material to repair small AF defects or to
      be used in combination with other biomaterials as an adhesive for larger defects.

PMID- 24684316
TI  - Comparison of two bioelectrical impedance devices and dual-energy X-ray
      absorptiometry to evaluate body composition in heart failure.
AB  - BACKGROUND: The utilisation of bioelectrical impedance analysis (BIA) in heart
      failure can be affected by many factors and its applicability remains
      controversial. The present study aimed to verify the adequacy of single-frequency
      BIA (SF-BIA) and multifrequency BIA (MF-BIA) compared to dual-energy x-ray
      absorptiometry (DEXA) for evaluating body composition in outpatients with heart
      failure. METHODS: In this cross-sectional study, 55 patients with stable heart
      failure and left ventricle ejection fraction <=45% were evaluated for fat mass
      percentage, fat mass and fat-free mass by DEXA and compared with the results
      obtained by SF-BIA (single frequency of 50 kHz) and MF-BIA (frequencies of 20 and
      100 kHz). RESULTS: MF-BIA and DEXA gave similar mean values for fat mass
      percentage, fat mass and fat-free mass, whereas values from SF-BIA were
      significantly different from DEXA. Both SF-BIA and MF-BIA measures of body
      composition correlated strongly with DEXA (r > 0.8; P < 0.001), except for fat
      mass assessed by SF-BIA, which showed a moderate correlation (r = 0.760; P <
      0.001). MF-BIA also showed a better agreement with DEXA by Bland-Altman analysis
      in all measurements. However, both types of equipment showed wide limits of
      agreement and a significant relationship between variance and bias (Pitmans's
      test P > 0.05), except MF-BIA for fat-free mass. CONCLUSIONS: Compared with DEXA,
      MF-BIA showed better accuracy than SF-BIA, although both types of equipment
      showed wide limits of agreement. The BIA technique should be used with caution,
      and regression equations might be useful for correcting the observed variations,
      mainly in extreme values of body composition.

PMID- 24684317
TI  - Asymmetric isomerization of omega-hydroxy-alpha,beta-unsaturated thioesters into
      beta-mercaptolactones by a bifunctional aminothiourea catalyst.
AB  - We present a novel methodology for the asymmetric synthesis of beta
      mercaptolactones via isomerization of omega-hydroxy-alpha,beta-unsaturated
      thioesters by means of a bifunctional aminothiourea catalyst. The catalyst
      interacts with the substrate through the cooperative action of both a covalent
      bond at the amino group and noncovalent bonding at the thiourea group. The
      potential for an enantiodivergent synthesis could also be demonstrated by
      carrying out the reaction in a different solvent system. 

PMID- 24684318
TI  - Timing of transjugular intrahepatic portosystmic for Budd-Chiari syndrome: still
      an open issue.

PMID- 24684320
TI  - Emergence of TEM, SHV, and CTX-M-extended spectrum beta-lactamases and class 1
      integron among Enterobacter cloacae isolates collected from hospitals of Tehran
      and Qazvin, Iran.
AB  - Extended-spectrum beta-lactamase (ESBL) production is an important resistance
      mechanism among clinical isolates of Enterobacter cloacae. TEM, SHV, and CTX-M
      are the most common ESBL genotypes among Enterobacter spp. The main aims of this
      study were to determine the antimicrobial susceptibility pattern and to detect
      ESBL-encoding genes as well as intI1 genes. One hundred twenty isolates of E.
      cloacae were collected from hospitals of Tehran and Qazvin, Iran. The isolates
      were identified by standard laboratory methods and API 20E strips. ESBL screening
      was performed by the combined disk method. PCR and sequencing were conducted for
      detection of ESBL-encoding genes as well as intI1 genes. Clonal relatedness of
      ESBL-producing isolates was assessed by the enterobacterial repetitive intergenic
      consensus (ERIC)-PCR method. Of 120 isolates, 57 (47.5%) were characterized as
      multidrug resistant among those 48 (84.2%) isolates carried class 1 integron.
      Fifty-three (44.2%) isolates were found to be ESBL producers, in which bla(CTX-M
      15) (60.4%) was the most common gene followed by bla(TEM-1) (32.1%), bla(TEM-169)
      (13.2%), and bla(SHV-12) (7.5%) either alone or in combination. Forty-four of the
      53 (83.01%) ESBL-producing isolates were genetically unrelated. For the first
      time, this study describes the emergence of TEM-169, SHV-12, and CTX-M-15 ESBL
      genotypes in E. cloacae isolates in Iran.

PMID- 24684319
TI  - Understanding the genetic control and physiological traits associated with
      rhizosheath production by barley (Hordeum vulgare).
AB  - There is an urgent need for simple rapid screens of root traits that improve the
      acquisition of nutrients and water. Temperate cereals produce rhizosheaths of
      variable weight, a trait first noted on desert species sampled by Tansley over
      100 yr ago. This trait is almost certainly important in tolerance to abiotic
      stress. Here, we screened association genetics populations of barley for
      rhizosheath weight and derived quantitative trait loci (QTLs) and candidate
      genes. We assessed whether rhizosheath weight was correlated with plant
      performance and phosphate uptake under combined drought and phosphorus
      deficiency. Rhizosheath weight was investigated in relation to root hair length,
      and under both laboratory and field conditions. Our data demonstrated that
      rhizosheath weight was correlated with phosphate uptake under dry conditions and
      that the differences in rhizosheath weight between genotypes were maintained in
      the field. Rhizosheath weight also varied significantly within barley
      populations, was correlated with root hair length and was associated with a
      genetic locus (QTL) on chromosome 2H. Putative candidate genes were identified.
      Rhizosheath weight is easy and rapid to measure, and is associated with
      relatively high heritability. The breeding of cereal genotypes for beneficial
      rhizosheath characteristics is achievable and could contribute to agricultural
      sustainability in nutrient- and water-stressed environments.

PMID- 24684321
TI  - Medullary thyroid carcinoma preferentially secreting procalcitonin.

PMID- 24684322
TI  - Artificially deformed crania from the Hun-Germanic Period (5th-6th century ad) in
      northeastern Hungary: historical and morphological analysis.
AB  - From an anthropological point of view, artificial deformation of the cranial
      shape in newborns is one of the most interesting human customs, which has been
      recorded in all continents and in different cultures. However, the main goals of
      this procedure were basically the same everywhere; that is, to distinguish
      certain groups of people from others and to indicate the social status of
      individuals. In the Carpathian Basin all artificially deformed skulls are dated
      to the late Iron Age, especially to the early Migration Period. The authors
      examined 9 artificially deformed skulls from the Hun-Germanic Period (5th-6th
      century ad) excavated from two cemeteries in the northeastern part of the Great
      Hungarian Plain (Hungary). The extent and the type of the deformation as well as
      the technique were determined in each case. The authors also attempt to shed
      light on the probable origin and the historical context of the custom practiced
      in the Carpathian Basin (Hungary), relying on the anthropological and historical
      literature on the Hun-Germanic and preceding periods. It seems possible that this
      custom, which is associated with the finds in the Carpathian Basin, first
      appeared in the Kalmykia steppe, later in the Crimea, from where it spread to
      Central and Western Europe by way of the Hun migration. Neither the cranial find
      described presently nor the special literature on the subject furnish convincing
      evidence that the cranial deformation resulted in any chronic neurological
      disorder. 

PMID- 24684323
TI  - Cardiac standstill and circulatory flow arrest in surgical treatment of
      intracranial aneurysms: a historical review.
AB  - Since the first surgery for an intracranial aneurysm in 1931, neurological
      surgeons have long strived to determine the optimal methods of surgical
      correction. Significant challenges of aneurysm clipping include intraoperative
      rupture and complex dome morphology. Hypothermia, cardiopulmonary bypass,
      pharmacologically induced hypotension, and cardiac standstill are a few of the
      methodologies historically and currently employed in the management of these
      issues. In the 1980s, significant advances in pharmacology and anesthesiology led
      to the use of agents such as adenosine for chemically induced hypotension and
      eventually complete circulatory arrest. Since the institution of the use of these
      agents, the traditional methods of circulatory arrest under conditions of
      hypothermia and cardiopulmonary bypass have fallen out of favor. However, there
      still exists a subset of technically difficult aneurysms for which cardiac
      standstill, both chemical and hypothermic, remains a viable therapeutic option.
      In this paper, the authors describe the history of cardiac standstill by both
      hypothermic and chemically induced means as well as provide examples in which
      these techniques are still necessary. 

PMID- 24684324
TI  - Expanding the borders: the evolution of neurosurgical approaches.
AB  - In this article the authors discuss the development of neurosurgical approaches
      and the advances in science and technology that influenced this development
      throughout history. They provide a broad overview of this interesting topic from
      the first attempts of trephination by ancient cultures to the work of the
      pioneers of neurosurgery and the introduction of microsurgery. 

PMID- 24684325
TI  - The history of neurosurgery and its relation to the development and refinement of
      the frontotemporal craniotomy.
AB  - The history of neurosurgery is filled with descriptions of brave surgeons
      performing surgery against great odds in an attempt to improve outcomes in their
      patients. In the distant past, most neurosurgical procedures were limited to
      trephination, and this was sometimes performed for unclear reasons. Beginning in
      the Renaissance and accelerating through the middle and late 19th century, a
      greater understanding of cerebral localization, antisepsis, anesthesia, and
      hemostasis led to an era of great expansion in neurosurgical approaches and
      techniques. During this process, frontotemporal approaches were also developed
      and refined over time. Progress often depended on the technical advances of
      scientists coupled with the innovative ideas and courage of pioneering surgeons.
      A better understanding of this history provides insight into where we originated
      as a specialty and in what directions we may go in the future. This review
      considers the historical events enabling the development of neurosurgery as a
      specialty, and how this relates to the development of frontotemporal approaches. 

PMID- 24684326
TI  - Craniotomy for anterior cranial fossa meningiomas: historical overview.
AB  - The surgical treatment of meningiomas located at the base of the anterior cranial
      fossa is often challenging, and the evolution of the surgical strategy to resect
      these tumors parallels the development of craniotomy, and neurosurgery in
      general, over the past century. Early successful operations to treat these tumors
      were pioneered by prominent figures such as Sir William Macewen and Francesco
      Durante. Following these early reports, Harvey Cushing made significant
      contributions, allowing a better understanding and treatment of meningiomas in
      general, but particularly those involving the anterior cranial base. Initially,
      large-sized unilateral or bilateral craniotomies were necessary to approach these
      deep-seated lesions. Technical advances such as the introduction of
      electrosurgery, the operating microscope, and refined microsurgical instruments
      allowed neurosurgeons to perform less invasive surgical procedures with better
      results. Today, a wide variety of surgical strategies, including endoscopic
      surgery and radiosurgery, are used to treat these tumors. In this review, the
      authors trace the evolution of craniotomy for anterior cranial fossa meningiomas.

PMID- 24684327
TI  - Making the "inoperable" tumors "operable": Harvey Cushing's contributions to the
      surgery of posterior fossa tumors.
AB  - Harvey Cushing played a pivotal role in establishing neurosurgery as a distinct
      surgical discipline. One of his most important contributions was defining the
      surgical removal of posterior fossa tumors. Compulsive preoperative evaluation
      followed by meticulous surgical technique as well as incorporation of maneuvers
      such as ventricular puncture and electrocautery further advanced resection of
      tumors in this region. Herein, the authors review Cushing's contributions to
      posterior fossa surgery. 

PMID- 24684329
TI  - Craniosynostosis surgery: the legacy of Paul Tessier.
AB  - Paul Louis Tessier is recognized as the father of craniofacial surgery. While his
      story and pivotal contributions to the development of the multidisciplinary
      practice of craniofacial surgery are much highlighted in plastic surgery
      literature, they are seldom directly discussed in the context of neurosurgeons.
      His life and legacy to craniosynostosis and neurosurgery are explored in the
      present paper. 

PMID- 24684328
TI  - Odilon Marc Lannelongue (1840-1911) and strip craniectomy for craniosynostosis.
AB  - In the 19th century, Dr. Odilon Marc Lannelongue was a pioneering French surgeon
      who introduced a surgical technique for the treatment of craniosynostosis. In
      1890, Dr. Lannelongue performed correction of sagittal synostosis by strip
      craniectomy. From his procedure, multiple techniques have been developed and
      endorsed for this condition, ranging from simple suturectomies to extensive
      calvarial vault remodeling. In addition, even today, endoscopically aided strip
      craniectomy is performed as a surgical treatment of craniosynostosis. This
      article describes the life and works of the surgeon who revolutionized the
      management of craniosynostosis. 

PMID- 24684330
TI  - The history of military cranioplasty.
AB  - There is evidence that the neurosurgical procedure of cranioplasty is as ancient
      as its better-known counterpart, trephination. With origins in pre-Incan Peru,
      cranioplasty remains an important reconstructive procedure for modern
      craniofacial surgery teams to master. Solutions to the often challenging problem
      of repairing skull defects continue to evolve to improve patient outcomes.
      Throughout recorded history, advances in cranioplasty have paralleled major
      military conflicts due to survivorship after trephination or decompressive
      craniectomy. Primitive skull coverings used in Peru were later replaced during
      the Middle Ages by grafts obtained in animals and humans. Improved survivorship
      secondary to advances in anesthesia and battlefield medicine during the Crimean
      War and the American Civil War allowed the use of tantalum and acrylic
      cranioplasty to evolve during World Wars I and II. In the modern era of the Iraq
      and Afghanistan conflicts, greater survivorship after cranial injury due to
      improvements in protective armor, medical evacuation, and early "far-forward"
      neurosurgical treatment have occurred. Consequently, the last decade has seen
      great advancement in cranial defect reconstruction, including custom-fabricated
      alloplast implants and the emergence of regenerative cranial treatments such as
      distraction osteogenesis, protected bone regeneration, and free tissue transfers.
      Comprehensive rehabilitation after neurotrauma has emerged as the new standard of
      care. 

PMID- 24684331
TI  - Materials used in cranioplasty: a history and analysis.
AB  - Cranioplasty, one of the oldest surgical procedures used to repair cranial
      defects, has undergone many revolutions over time to find the ideal material to
      improve patient prognosis. Cranioplasty offers cosmetic and protective benefits
      for patients with cranial defects. The first primitive cranioplasty procedures
      date back to 7000 bc and used metal and gourds to repair cranial defects.
      Cranioplasty was first documented by Fallopius who described repair using gold
      plates; the first bone graft was documented by van Meekeren. The first
      significant improvement for this procedure began with experimentation involving
      bone grafts in the late 19th century as a more natural approach for repairing
      cranial defects. The next impetus for advancement came because of wartime
      injuries incurred during World Wars I and II and involved experimentation with
      synthetic materials to counter the common complications associated with bone
      grafts. Methyl methacrylate, hydroxyapatite, ceramics, and polyetheretherketone
      implants among other materials have since been researched and used. Research now
      has shifted toward molecular biology to improve the ability of the patient to
      regenerate bone using bone growth factors. This paper reviews the evolution of
      materials used over time in addition to the various advantages and pitfalls
      associated with each change. It is important for neurosurgeons to be mindful of
      how these techniques have evolved in order to gain a better understanding of this
      procedure and how it has been adapted. 

PMID- 24684332
TI  - A brief history of early neuroanesthesia.
AB  - Two key discoveries in the 19th century--infection control and the development of
      general anesthesia--provided an impetus for the rapid advancement of surgery,
      especially within the field of neurosurgery. Improvements in anesthesia and
      perioperative care, in particular, fostered the development of meticulous
      surgical technique conducive to the refinement of neuroanatomical understanding
      and optimization of neurosurgical procedures and outcomes. Yet, even dating back
      to the earliest times, some form of anesthesia or perioperative pain management
      was used during neurosurgical procedures. Despite a few reports on anesthesia
      published around the time of William Morton's now-famous public demonstration of
      ether anesthesia in 1846, relatively little is known or written of early
      anesthetics in neurosurgery. In the present article the authors discuss the
      history of anesthesia pertaining to neurosurgical procedures and draw parallels
      between the refinements and developments in anesthesia care over time with some
      of the concomitant advances in neurosurgery.

PMID- 24684333
TI  - History of synthetic materials in alloplastic cranioplasty.
AB  - When faced with calvarial defects, surgeons have long searched for repair
      materials. General criteria include ease of use, low cost, availability, cosmetic
      shape, and osteointegrative potential. While autologous bone is widely used and
      favored in contemporary reconstructive procedures, synthetic alternatives have
      been used throughout history and are necessary in current practice for select
      cases when autograft reconstruction is not an option (such as cases with severe
      bony comminution, bone graft resorption, infection, and limited donor site
      options). For centuries, surgeons have experimented with metals, ceramics,
      plastics, and later, resorbable polymers. This paper provides a tour of the
      materials that have been used and experimented with throughout the history of
      alloplastic cranioplasty. 

PMID- 24684334
TI  - The Reverend Russell H. Conwell, W. Wayne Babcock, and the "soup bone"
      cranioplasties of 1915.
AB  - In 1915, faced with 2 patients with large skull defects, W. Wayne Babcock, an
      obstetrician-gynecologist-turned-general surgeon, operating in a modest North
      Philadelphia hospital, did something extraordinary: he went to the hospital
      kitchen to look for a cranial graft. Based heavily on archival and other primary
      sources, the authors tell the remarkable tale of the "soup bone" cranioplasties
      of the Samaritan Hospital and place these operations within the context of the
      early modern American hospital. 

PMID- 24684335
TI  - World War II, tantalum, and the evolution of modern cranioplasty technique.
AB  - Cranioplasty is a unique procedure with a rich history. Since ancient times, a
      diverse array of materials from coconut shells to gold plates has been used for
      the repair of cranial defects. More recently, World War II greatly increased the
      demand for cranioplasty procedures and renewed interest in the search for a
      suitable synthetic material for cranioprostheses. Experimental evidence revealed
      that tantalum was biologically inert to acid and oxidative stresses. In fact, the
      observation that tantalum did not absorb acid resulted in the metal being named
      after Tantalus, the Greek mythological figure who was condemned to a pool of
      water in the Underworld that would recede when he tried to take a drink. In
      clinical use, malleability facilitated a single-stage cosmetic repair of cranial
      defects. Tantalum became the preferred cranioplasty material for more than 1000
      procedures performed during World War II. In fact, its use was rapidly adopted in
      the civilian population. During World War II and the heyday of tantalum
      cranioplasty, there was a rapid evolution in prosthesis implantation and fixation
      techniques significantly shaping how cranioplasties are performed today. Several
      years after the war, acrylic emerged as the cranioplasty material of choice. It
      had several clear advantages over its metallic counterparts. Titanium, which was
      less radiopaque and had a more optimal thermal conductivity profile (less
      thermally conductive), eventually supplanted tantalum as the most common metallic
      cranioplasty material. While tantalum cranioplasty was popular for only a decade,
      it represented a significant breakthrough in synthetic cranioplasty. The
      experiences of wartime neurosurgeons with tantalum cranioplasty played a pivotal
      role in the evolution of modern cranioplasty techniques and ultimately led to a
      heightened understanding of the necessary attributes of an ideal synthetic
      cranioplasty material. Indeed, the history of tantalum cranioplasty serves as a
      model for innovative thinking and adaptive technology development. 

PMID- 24684336
TI  - The history of urea as a hyperosmolar agent to decrease brain swelling.
AB  - In 1919, it was observed that intravascular osmolar shifts could collapse the
      thecal sac and diminish the ability to withdraw CSF from the lumbar cistern. This
      led to the notion that hyperosmolar compounds could ameliorate brain swelling.
      Since then, various therapeutic interventions have been used for the reduction of
      intracranial pressure and brain volume. Urea was first used as an osmotic agent
      for the reduction of brain volume in 1950. It was associated with greater
      efficacy and consistency than alternatives such as hyperosmolar glucose. Its use
      became the standard of clinical practice by 1957, in both the intensive care unit
      and operating room, to reduce intracranial pressure and brain bulk and was the
      first hyperosmolar compound to have widespread use. However, the prime of urea
      was rather short lived. Reports of side effects and complications associated with
      urea emerged. These included coagulopathy, hemoglobinuria, electrocardiography
      changes, tissue necrosis with extravasation, and a significant potential for
      rebound intracranial hypertension. Mannitol was introduced in 1961 as a
      comparable and potentially superior alternative to urea. However, mannitol was
      initially purported to be less effective at rapidly reducing intracranial
      pressure. The debate over the two compounds continued for a decade until mannitol
      eventually replaced urea by the late 1960s and early 1970s as the hyperosmolar
      agent of choice due to the ease of preparation, chemical stability, and decreased
      side effect profile. Although urea is not currently the standard of care today,
      its rise and eventual replacement by mannitol played a seminal role in both our
      understanding of cerebral edema and the establishment of strategies for its
      management. 

PMID- 24684337
TI  - From the notch to a glioma grading system: the neurological contributions of
      James Watson Kernohan.
AB  - During his lifetime and a career spanning 42 years, James Watson Kernohan made
      numerous contributions to neuropathology, neurology, and neurosurgery. One of
      these, the phenomenon of ipsilateral, false localizing signs caused by
      compression of the contralateral cerebral peduncle against the tentorial edge,
      has widely become known as "Kernohan's notch" and continues to bear his name. The
      other is a grading system for gliomas from a neurosurgical viewpoint that
      continues to be relevant for grading of glial tumors 60 years after its
      introduction. In this paper, the authors analyze these two major contributions in
      detail within the context of Kernohan's career and explore how they contributed
      to the development of neurosurgical procedures. 

PMID- 24684338
TI  - The early days of hemostasis in neurosurgery.
AB  - Two key discoveries in the 19th century--infection control and the development of
      general anesthesia--provided an impetus for the rapid advancement of surgery,
      especially within the field of neurosurgery. Yet the field of neurosurgery would
      not have existed in the modern sense without the development and advancement of
      techniques in hemostasis. Improvement in intraoperative hemostasis came more
      gradually but was no less important to enhancing neurosurgical outcomes. The
      history of hemostasis in neurosurgery is often overlooked. Herein, the authors
      briefly review the historical progression of hemostatic techniques since the
      beginning of the early modern era of neurosurgery.

PMID- 24684339
TI  - Berengario's drill: origin and inspiration.
AB  - Craniotomies are among the oldest neurosurgical procedures, as evidenced by early
      human skulls discovered with holes in the calvaria. Though devices change, the
      principles to safely transgress the skull are identical. Modern neurosurgeons
      regularly use electric power drills in the operating theater; however,
      nonelectric trephining instruments remain trusted by professionals in certain
      emergent settings in the rare instance that an electric drill is unavailable.
      Until the late Middle Ages, innovation in craniotomy instrumentation remained
      stunted without much documented redesign. Jacopo Berengario da Carpi's (c. 1457
      1530 CE) text Tractatus de Fractura Calvae sive Cranei depicts a drill previously
      unseen in a medical volume. Written in 1518 CE, the book was motivated by defeat
      over the course of Lorenzo II de'Medici's medical care. Berengario's
      interchangeable bit with a compound brace ("vertibulum"), known today as the
      Hudson brace, symbolizes a pivotal device in neurosurgery and medical tool
      design. This drill permitted surgeons to stock multiple bits, perform the
      craniotomy faster, and decrease equipment costs during a period of increased
      incidence of cranial fractures, and thus the need for craniotomies, which was
      attributable to the introduction of gunpowder. The inspiration stemmed from a
      school of thought growing within a population of physicians trained as
      mathematicians, engineers, and astrologers prior to entering the medical
      profession. Berengario may have been the first to record the use of such a unique
      drill, but whether he invented this instrument or merely adapted its use for the
      craniotomy remains clouded. 

PMID- 24684340
TI  - The history of craniotomy for headache treatment.
AB  - Both the history of headache and the practice of craniotomy can be traced to
      antiquity. From ancient times through the present day, numerous civilizations and
      scholars have performed craniotomy in attempts to treat headache. Today, surgical
      intervention for headache management is becoming increasingly more common due to
      improved technology and greater understanding of headache. By tracing the
      evolution of the understanding of headache alongside the practice of craniotomy,
      investigators can better evaluate the mechanisms of headache and the therapeutic
      treatments used today. 

PMID- 24684341
TI  - History of craniotomy, cranioplasty, and perioperative care.

PMID- 24684342
TI  - Nitrogen oxides as a chemistry trap in detonating oxygen-rich materials.
AB  - Despite decades of research, the chemical processes and states of matter that
      govern the behavior of energetic materials under detonation conditions are not
      well understood, including the molecular-level processes that determine
      decomposition kinetics and energy release. Oxygen content is often employed as a
      simple and intuitive guide to the development and practical use of explosives,
      but its effect on detonation chemistry remains little studied, especially for the
      case of oxygen overabundance. To this end, we have conducted quantum molecular
      dynamics (QMD) simulations of zero oxygen balance and oxygen-rich mixtures of
      hydrogen peroxide and nitromethane under detonation-like conditions to near
      equilibrium time scales. We find excellent agreement between our extrapolated
      chemical equilibrium properties and those from thermochemical models for the zero
      oxygen balance mixture. In contrast, for the oxygen-rich mixture, we observe the
      formation of nitrogen oxide intermediates, particularly nitrate ions (NO3), that
      effectively act as an oxygen/nitrogen "trap" by precluding the formation of the
      equilibrium products N2 and CO2. Our results could have implications for the
      design and modeling of oxygen-rich energetics in common military and industrial
      use. 

PMID- 24684343
TI  - Anatomy of hepatic arteriolo-portal venular shunts evaluated by 3D micro-CT
      imaging.
AB  - The liver differs from other organs in that two vascular systems deliver its
      blood - the hepatic artery and the portal vein. However, how the two systems
      interact is not fully understood. We therefore studied the microvascular geometry
      of rat liver hepatic artery and portal vein injected with the contrast polymer
      Microfil((r)). Intact isolated rat livers were imaged by micro-CT and anatomic
      evidence for hepatic arteriolo-portal venular shunts occurring between hepatic
      artery and portal vein branches was found. Simulations were performed to rule out
      the possibility of the observed shunts being artifacts resulting from image
      blurring. In addition, in the case of specimens where only the portal vein was
      injected, only the portal vein was opacified, whereas in hepatic artery
      injections, both the hepatic artery and portal vein were opacified. We conclude
      that mixing of the hepatic artery and portal vein blood can occur proximal to the
      sinusoidal level, and that the hepatic arteriolo-portal venular shunts may
      function as a one-way valve-like mechanism, allowing flow only from the hepatic
      artery to the portal vein (and not the other way around).

PMID- 24684344
TI  - Hypothermic cutaneous collagenous vasculopathy with centrifugal spreading.

PMID- 24684345
TI  - Statins are associated with decreased mortality risk after status epilepticus.
AB  - BACKGROUND AND PURPOSE: Statins display anti-inflammatory and anti-epileptogenic
      properties in animal models, and may reduce the epilepsy risk in elderly humans;
      however, a possible modulating role on outcome in patients with status
      epilepticus (SE) has not been assessed. METHODS: This cohort study was based on a
      prospective registry including all consecutive adults with incident SE treated in
      our center between April 2006 and September 2012. SE outcome was categorized at
      hospital discharge into 'return to baseline', 'new disability' and 'mortality'.
      The role of potential predictors, including statins treatment on admission, was
      evaluated using a multinomial logistic regression model. RESULTS: Amongst 427
      patients identified, information on statins was available in 413 (97%). Mean age
      was 60.9 (+/-17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal
      SE etiology; and 191 (46%) experienced generalized-convulsive or non-convulsive
      SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed
      prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%)
      patients returned to baseline, 58 (14%) died. After adjustment for established SE
      outcome predictors (age, etiology, SE severity score), statins correlated
      significantly with lower mortality (relative risk ratio 0.38, P = 0.046).
      CONCLUSION: This study suggests for the first time that exposure to statins
      before an SE episode is related to its outcome, involving a possible anti
      epileptogenic role. Other studies are needed to confirm this intriguing finding.

PMID- 24684346
TI  - Mesenchymal stem cells in grafts failed to engraft in the bone marrow
      microenvironment of a leukemia patient post HLA-match and haplo-identical
      allogeneic hematopoietic stem cell transplantations.

PMID- 24684347
TI  - Birinapant, a smac-mimetic with improved tolerability for the treatment of solid
      tumors and hematological malignancies.
AB  - Birinapant (1) is a second-generation bivalent antagonist of IAP proteins that is
      currently undergoing clinical development for the treatment of cancer. Using a
      range of assays that evaluated cIAP1 stability and oligomeric state, we
      demonstrated that 1 stabilized the cIAP1-BUCR (BIR3-UBA-CARD-RING) dimer and
      promoted autoubiquitylation of cIAP1 in vitro. Smac-mimetic 1-induced loss of
      cIAPs correlated with inhibition of TNF-mediated NF-kappaB activation, caspase
      activation, and tumor cell killing. Many first-generation Smac-mimetics such as
      compound A (2) were poorly tolerated. Notably, animals that lack functional
      cIAP1, cIAP2, and XIAP are not viable, and 2 mimicked features of triple IAP
      knockout cells in vitro. The improved tolerability of 1 was associated with (i)
      decreased potency against cIAP2 and affinity for XIAP BIR3 and (ii) decreased
      ability to inhibit XIAP-dependent signaling pathways. The P2' position of 1 was
      critical to this differential activity, and this improved tolerability has
      allowed 1 to proceed into clinical studies. 

PMID- 24684348
TI  - Characterization of antimicrobial resistance of Vibrio parahaemolyticus from
      cultured sea cucumbers (Apostichopus japonicas).
AB  - This study was aimed to evaluate the antimicrobial resistance and molecular
      resistance mechanisms of 87 Vibrio parahaemolyticus isolates from cultured sea
      cucumbers (Apostichopus japonicus). The results showed that all isolates were
      resistant to ampicillin and cephazolin, fewer of them were resistant to
      streptomycin (43.7%), cefuroxime sodium (18.4%), tetracycline (4.6%),
      sulphamethoxazole/trimethoprim (2.3%) and four quinolones (2.3%). More than half
      (56.2%) of the isolates displayed multiple resistance to at least three
      antimicrobials. The resistance genes were detected in all antimicrobial-resistant
      isolates except two tetracycline-resistant isolates. Among all these tested
      resistance genes, blaTEM , sul2, strA and strB were predominant, and none of
      blaSHV , blaCTX-M , blaOXA , sul1, sul3, tetA, tetM and tetQ genes was detected.
      Point mutations were found in quinolone resistance-determining regions of gyrA
      and parC genes in quinolone-resistant isolates. All isolates harboured class 1
      integrons but only one carried gene cassette without any resistance genes, and
      none of them was positive to class 2, 3 integrons and SXT constins. These results
      indicate that the antimicrobial-resistant V. parahaemolyticus isolates from sea
      cucumbers and resistance genes could be potential risks to public health or other
      environments. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first
      report on characterization of antimicrobial resistance of Vibrio parahaemolyticus
      from sea cucumbers (Apostichopus japonicus). Our findings reveal a high level of
      resistance to some antimicrobials and prevalence of the resistance genes in V.
      parahaemolyticus isolates from sea cucumbers and underline the need for prudent
      use of antimicrobials in aquaculture to minimize the spread of antimicrobial
      resistant V. parahaemolyticus.

PMID- 24684349
TI  - Covariates of condom use in South Africa: findings from a national population
      based survey in 2008.
AB  - Condom use has increased significantly over the past decade among all adult age
      groups in South Africa, and it is widely believed to have played a major role in
      the recent significant decline in HIV incidence in the country, especially among
      young people. This study investigated the demographic, behavioural and
      psychosocial correlates of condom use at last sex among a national random
      probability sample of sexually experienced respondents aged 15 years and older (n
      = 7817, 42.9% males and 57.1% females) using data from the 2008 South African
      national HIV population-based household survey. Multivariate logistic regression
      analyses revealed that for both sexes, being aged 15-24 years and 25-49 years
      old, Black African, never married and unemployed were significantly associated
      with condom use at last sex. In addition, for males, condom use was associated
      with having had two or more sexual partners, whereas for females it was
      associated with living in urban formal, urban informal and rural informal areas,
      and having been in a current relationship for less than a year. Based on these
      findings, it was concluded that there is a need to further promote condom use
      especially among the subgroups of people with lower rates of condom use in order
      to reduce their risk of HIV infection.

PMID- 24684350
TI  - SOX11 and TP53 add prognostic information to MIPI in a homogenously treated
      cohort of mantle cell lymphoma--a Nordic Lymphoma Group study.
AB  - Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has
      been remarkably improved by use of protocols including high dose cytarabine,
      rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3
      protocols. In 2008, a MCL international prognostic index (MIPI) was created to
      enable stratification of the clinical diverse MCL patients into three risk
      groups. So far, use of the MIPI in clinical routine has been limited, as it has
      been shown that it inadequately separates low and intermediate risk group
      patients. To improve outcome and minimize treatment-related morbidity, additional
      parameters need to be evaluated to enable risk-adapted treatment selection. We
      have investigated the individual prognostic role of the MIPI and molecular
      markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1).
      Furthermore, we explored the possibility of creating an improved prognostic tool
      by combining the MIPI with information on molecular markers. SOX11 was shown to
      significantly add prognostic information to the MIPI, but in multivariate
      analysis TP53 was the only significant independent molecular marker. Based on
      these findings, we propose that TP53 and SOX11 should routinely be assessed and
      that a combined TP53/MIPI score may be used to guide treatment decisions. 

PMID- 24684351
TI  - Dipeptidyl peptidase-4 inhibitors: pharmacokinetics, efficacy, tolerability and
      safety in renal impairment.
AB  - The dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of blood glucose
      lowering therapy with proven efficacy, tolerability and safety. Four of the five
      commercially available DPP-4 inhibitors are subject to significant renal
      clearance, and pharmacokinetic studies in people with renal impairment have led
      to lower recommended doses based on creatinine clearance in order to prevent drug
      accumulation. Data from these pharmacokinetic studies and from supratherapeutic
      doses in healthy individuals and people with uncomplicated diabetes during
      development suggest, however, that there is a wide therapeutic margin. This
      should protect against toxicity if people with renal impairment are inadvertently
      prescribed higher doses than recommended. Doses appropriate to renal function are
      associated with reductions in HbA1c that are equivalent to those observed in
      people with type 2 diabetes who do not have renal impairment. Recent large-scale
      cardiovascular safety trials of saxagliptin and alogliptin have identified heart
      failure as a potential concern and renal impairment may increase the risk of this
      complication. Although the incidence of pancreatitis does not appear to be
      significantly increased by DPP-4 inhibitor therapy, renal impairment is also an
      independent risk factor. Additional data from other ongoing DPP-4 inhibitor
      cardiovascular safety trials should provide a more precise assessment of the
      risks of these uncommon complications, including in people with renal impairment.

PMID- 24684352
TI  - Naringenin attenuates CCl4 -induced hepatic inflammation by the activation of an
      Nrf2-mediated pathway in rats.
AB  - The possible protective effects of naringenin, a naturally occurring citrus
      flavonone, on carbon tetrachloride (CCl4 )-induced liver injury in rats and the
      mechanism underlying its effects were investigated. Forty rats were divided into
      five groups. Rats in Groups I and II served as the normal and injured liver
      groups, respectively; Group III rats were treated with the standard drug
      silymarin as a positive control; and rats in Groups IV and V (naringenin-treated
      groups) were administrated 50 mg/kg, p.o., naringenin for 7 days. Liver samples
      were collected to evaluate mRNA and protein expression, histological changes and
      oxidative stress. Naringenin inhibited lipid peroxidation and reduced serum
      levels of hepatic enzymes induced by CCl4 . In addition, naringenin increased the
      liver content of reduced glutathione and the activity of anti-oxidant enzymes in
      rats treated with CCl4 . Naringenin attenuated liver inflammation by
      downregulating CCl4 -induced activation of tumour necrosis factor (TNF)-alpha,
      inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX-2) at both the
      protein and mRNA levels. Naringenin treatment significantly increased NF-E2
      related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers.
      In rats treated with CCl4 alone, decreases were seen in nuclear Nrf2 expression
      and in the mRNA levels of its target genes (e.g. HO-1, NQO1 and glutathione S
      transferase alpha 3 (GST-a3)). Together, the results suggest that naringenin can
      protect the liver against oxidative stress, presumably by activating the nuclear
      translocation of Nrf2 as well as attenuating the TNF-alpha pathway to elicit an
      anti-inflammatory response in liver tissue. 

PMID- 24684353
TI  - Generalizability and singularity. The crossroads between science and clinical
      practice.

PMID- 24684354
TI  - Developing a research agenda for primary prevention of chronic lung diseases--an
      NHLBI perspective.

PMID- 24684355
TI  - Cystic fibrosis transmembrane conductance regulator and pseudomonas.

PMID- 24684356
TI  - The burden of disease and the need for a simple staging system in idiopathic
      pulmonary fibrosis.

PMID- 24684357
TI  - Tertiary lymphoid structures target the antitumor immune response to lung cancer.

PMID- 24684358
TI  - Mildly progressive pulmonary lymphangiectasis diagnosed in a young adult.

PMID- 24684359
TI  - Diaphragm fiber strength is reduced in critically ill patients and restored by a
      troponin activator.

PMID- 24684360
TI  - Depletion of circulating regulatory T cells during severe respiratory syncytial
      virus infection in young children.

PMID- 24684361
TI  - Obstructive sleep apnea and preclinical cardiac damage: need for U.S.
      representative study sample.

PMID- 24684362
TI  - Reply from the authors.

PMID- 24684363
TI  - The association between obstructive sleep apnea severity and N-terminal pro-B
      type natriuretic peptide levels in women.

PMID- 24684364
TI  - Nonlinear weight and chronic obstructive pulmonary disease effect modeling to
      improve data fitting.

PMID- 24684365
TI  - Reply from the authors.

PMID- 24684366
TI  - Bilateral diaphragm weakness after chemotherapy for lymphoma.

PMID- 24684367
TI  - Gene expression and morphometric parameters of human bone biopsies after
      maxillary sinus floor elevation with autologous bone combined with Bio-Oss(r) or
      BoneCeramic(r).
AB  - OBJECTIVES: Although the clinical success of Bio-Oss((r)) and BoneCeramic((r))
      has been corroborated by histologic and histomorphometric findings, the
      biological events that occur during healing after maxillary sinus floor elevation
      (MSFE) are unknown. Here, we evaluated biopsies of grafted bone with a mixture of
      autologous bone and Bio-Oss((r)) or BoneCeramic((r)) after two different healing
      time periods to understand the molecular process underlying bone formation after
      MSFE. MATERIAL AND METHODS: Seven patients, following a bilateral split-mouth
      design model and needing a MSFE to allow implant placement, were recruited for
      this study. Right or left sinuses were grafted with autologous maxillary bone
      combined either with Bio-Oss((r)) or BoneCeramic((r)) , respectively. Twenty
      biopsies were taken at the time of implant insertion after 4-5 months or 6-8
      months of MSFE, and analyzed by micro-computed tomography (microCT) and gene
      expression analysis. RESULTS: MicroCT analysis revealed no differences in the
      morphometric parameters or BMD either after 4-5 months or 6-8 months of MSFE
      between Bio-Oss((r)) and BoneCeramic((r)) . At molecular level, a higher
      expression of bone forming gene Runx2 was observed after 4-5 months of MSFE in
      the Bio-Oss((r)) compared with the BoneCeramic((r)) group. CONCLUSIONS: Our
      results indicate that differences found at the molecular level between Bio
      Oss((r)) and BoneCeramic((r)) are not translated to important differences in the
      3D microstructure and BMD of the grafted bone.

PMID- 24684368
TI  - Novel top-contact monolayer pentacene-based thin-film transistor for ammonia gas
      detection.
AB  - We report on the fabrication of an organic field-effect transistor (OFET) of a
      monolayer pentacene thin film with top-contact electrodes for the aim of ammonia
      (NH3) gas detection by monitoring changes in its drain current. A top-contact
      configuration, in which source and drain electrodes on a flexible stamp
      [poly(dimethylsiloxane)] were directly contacted with the monolayer pentacene
      film, was applied to maintain pentacene arrangement ordering and enhance the
      monolayer OFET detection performance. After exposure to NH3 gas, the carrier
      mobility at the monolayer OFET channel decreased down to one-third of its
      original value, leading to a several orders of magnitude decrease in the drain
      current, which tremendously enhanced the gas detection sensitivity. This
      sensitivity enhancement to a limit of the 10 ppm level was attributed to an
      increase of charge trapping in the carrier channel, and the amount of trapped
      states was experimentally evaluated by the threshold voltage shift induced by the
      absorbed NH3 molecular analyte. In contrast, a conventional device with a 50-nm
      thick pentacene layer displayed much higher mobility but lower response to NH3
      gas, arising from the impediment of analyte penetrating into the conductive
      channel, owing to the thick pentacene film. 

PMID- 24684369
TI  - Development of a novel headspace sorptive extraction method to study the aging of
      volatile compounds in spent handgun cartridges.
AB  - Estimating the time since the last discharge of firearms and/or spent cartridges
      may be a useful piece of information in forensic firearm-related cases. The
      current approach consists of studying the diffusion of selected volatile organic
      compounds (such as naphthalene) released during the shooting using solid-phase
      microextraction (SPME). However, this technique works poorly on handgun
      cartridges because the extracted quantities quickly fall below the limit of
      detection. In order to find more effective solutions and further investigate the
      aging of organic gunshot residue after the discharge of handgun cartridges, an
      extensive study was carried out in this work using a novel approach based on high
      capacity headspace sorptive extraction (HSSE). By adopting this technique, for
      the first time 51 gunshot residue (GSR) volatile organic compounds could be
      simultaneously detected from fired handgun cartridge cases. Application to aged
      specimens showed that many of those compounds presented significant and
      complementary aging profiles. Compound-to-compound ratios were also tested and
      proved to be beneficial both in reducing the variability of the aging curves and
      in enlarging the time window useful in a forensic casework perspective. The
      obtained results were thus particularly promising for the development of a new
      complete forensic dating methodology. 

PMID- 24684370
TI  - Sustained gene expression in the retina by improved episomal vectors.
AB  - Gene and cellular therapies are nowadays part of therapeutic strategies for the
      treatment of diverse pathologies. The drawbacks associated with gene therapy-low
      levels of transgene expression, vector loss during mitosis, and gene silencing
      need to be addressed. The pEPI-1 and pEPito family of vectors was developed to
      overcome these limitations. It contains a scaffold/matrix attachment region,
      which anchors its replication to cell division in eukaryotic cells while in an
      extrachromosomal state and is less prone to silencing, due to a lower number of
      CpG motifs. Recent success showed that ocular gene therapy is an important tool
      for the treatment of several diseases, pending the overcome of the aforementioned
      limitations. To achieve sustained gene delivery in the retina, we evaluated
      several vectors based on pEPito and pEPI-1 for their ability to sustain transgene
      expression in retinal cells. These vectors stably transfected and replicated in
      retinal pigment epithelial (RPE) cells. Expression levels were promoter dependent
      with constitutive promoters cytomegalovirus immediate early promoter (CMV) and
      human CMV enhancer/human elongation factor 1 alpha promoter yielding the highest
      levels of transgene expression compared with the retina-specific RPE65 promoter.
      When injected in C57Bl6 mice, transgene expression was sustained for at least 32
      days. Furthermore, the retina-specific RPE65 promoter showed higher efficiency in
      vivo compared to in vitro. In this study, we demonstrate that by combining tissue
      specific promoters with a mitotic stable system, less susceptible to epigenetic
      silencing such as pEPito-based plasmids, we can achieve prolonged gene expression
      and a sustained therapeutic effect. 

PMID- 24684371
TI  - Nutritional constituents and health benefits of wild rice (Zizania spp.).
AB  - Wild rice (Zizania spp.) seems to have originated in North America and then
      dispersed into Eastern Asia and other parts of the world. Nutritional analysis
      shows that wild rice is rich in minerals, vitamins, protein, starch, dietary
      fiber, and various antioxidant phytochemicals, while it is low in fat. Wild rice
      has been recognized as a whole grain by the US Food and Drug Administration; in
      the North American marketplace it is currently sold as and considered to be a
      health-promoting food. Recent scientific studies have revealed antioxidant and
      lipid-lowering properties of wild rice, while others have documented
      cardiovascular benefits associated with the long-term consumption of wild rice in
      experimental settings. The present review article summarizes various features of
      wild rice and its cultivation, including its plantation, harvest, nutritional
      composition, and biological properties. While evidence for the cardiovascular
      benefits of wild rice consumption is accumulating, additional studies are
      warranted to determine the clinical benefits of regular consumption of wild rice.

PMID- 24684373
TI  - Bioluminescent human thyrospheres allow noninvasive detection of anaplastic
      thyroid cancer growth and metastases in vivo.
AB  - BACKGROUND: We have previously demonstrated that thyrospheres derived from human
      anaplastic thyroid cancer (ATC) cell lines can reconstitute and sustain tumor
      growth in vivo. The aim of this study was to use luciferase-expressing
      thyrospheres to establish a clinically relevant mouse model of ATC that allows
      noninvasive and sensitive monitoring of tumor progression. METHODS: Two human ATC
      cell lines stably transfected with a firefly luciferase gene were used to
      generate thyrospheres under stem cell culture conditions. Cells were
      orthotopically implanted into the thyroids of immunodeficient NOD/SCIDIl2rg-/-
      mice to initiate tumors. Tumor progression and metastasis were evaluated by
      bioluminescent imaging weekly as well as histologic analysis postmortem. RESULTS:
      We show that only 100 thyrosphere cells are needed for tumor development, and
      that tumors can be monitored with bioluminescent imaging as early as 7-14 days
      after implantation. Subsequent histologic evaluation of tissue sections confirmed
      characteristics of high-grade malignant neoplasms. CONCLUSIONS: This approach
      offers rapid and highly sensitive noninvasive detection options for the
      preclinical assessment of novel ATC therapeutics in vivo.

PMID- 24684374
TI  - Surface selective one-step fabrication of carbon nanotube thin films with high
      density.
AB  - Thin films of carbon nanotubes (CNTs) are fabricated from solution using a one
      step directed assembly strategy. Very high surface selectivity and exceptionally
      high CNT densities can be observed in small features with complex shapes. This
      directed assembly technique makes use of minimum amounts of CNTs and low toxicity
      solvents, and can be applied to metallic, semiconducting and mixed CNTs for
      fabrication of thin films over macroscopic areas. The thin films obtained with
      this approach are used for thin-film transistor (TFT) fabrication, and their
      electrical characterization is described. 

PMID- 24684372
TI  - Glucocorticoid receptor deletion from the dorsal raphe nucleus of mice reduces
      dysphoria-like behavior and impairs hypothalamic-pituitary-adrenocortical axis
      feedback inhibition.
AB  - Glucocorticoids can cause depression and anxiety. Mechanisms for glucocorticoid
      effects on mood are largely undefined. The dorsal raphe nucleus (DRN) produces
      the majority of serotonin in the brain, and expresses glucocorticoid receptors
      (GR). Because we previously showed that antidepressants used to treat depression
      and anxiety decrease DRN GR expression, we hypothesized that deleting DRN GR
      would have anxiolytic- and antidepressant-like effects. We also hypothesized that
      DRN GR deletion would disinhibit activity of the hypothalamic-pituitary-adrenal
      (HPA) axis. Adeno-associated virus pseudotype AAV2/9 expressing either Cre
      recombinase (DRNGRKO mice) or GFP (DRN-GFP mice) was injected into the DRN of
      floxed GR mice to test these hypotheses. Three weeks after injection, mice
      underwent 21 days of social defeat or control handling and were tested for
      anxiety-like behavior (open-field test, elevated-plus maze), depression-like
      behavior [sucrose preference, forced-swim test (FST), tail-suspension test
      (TST)], social interaction, and circadian and stress-induced HPA activity. DRN GR
      deletion decreased anxiety-like behavior in control but not in defeated mice. DRN
      GR deletion decreased FST and tended to decrease TST despair-like behavior in
      both control and defeated mice, but did not affect sucrose preference.
      Exploration of social (a novel mouse) as well as neutral (an empty box) targets
      was increased in DRNGRKO mice, suggesting that DRN GR deletion also promotes
      active coping. DRN GR deletion increased stress-induced HPA activity without
      strongly altering circadian HPA activity. We have shown a novel role for DRN GR
      to mediate anxiety- and despair-like behavior and to regulate HPA negative
      feedback during acute stress. 

PMID- 24684376
TI  - The domestic horse harbours Y-chromosomal microsatellite polymorphism only on two
      widely distributed male lineages.

PMID- 24684375
TI  - Strong and selective adsorption of lysozyme on graphene oxide.
AB  - Biosensing methods and devices using graphene oxide (GO) have recently been
      explored for detection and quantification of specific biomolecules from body
      fluid samples, such as saliva, milk, urine, and serum. For a practical
      diagnostics application, any sensing system must show an absence of nonselective
      detection of abundant proteins in the fluid matrix. Because lysozyme is an
      abundant protein in these body fluids (e.g., around 21.4 and 7 MUg/mL of lysozyme
      is found in human milk and saliva from healthy individuals, and more than 15 or
      even 100 MUg/mL in patients suffering from leukemia, renal disease, and
      sarcoidosis), it may interfere with detections and quantification if it has
      strong interaction with GO. Therefore, one fundamental question that needs to be
      addressed before any development of GO based diagnostics method is how GO
      interacts with lysozyme. In this study, GO has demonstrated a strong interaction
      with lysozyme. This interaction is so strong that we are able to subsequently
      eliminate and separate lysozyme from aqueous solution onto the surface of GO.
      Furthermore, the strong electrostatic interaction also renders the selective
      adsorption of lysozyme on GO from a mixture of binary and ternary proteins. This
      selectivity is confirmed by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), fluorescence spectroscopy, and UV-vis absorption
      spectroscopy. 

PMID- 24684377
TI  - The effects of exposure in sandy beach surf zones on larval fishes.
AB  - The influence of wind and wave exposure on larval fish assemblages within a large
      bay system was investigated. Larval fishes were sampled from two areas with
      vastly different exposure to waves and wind, namely the windward and leeward
      sectors of Algoa Bay. In total, 5702 larval fishes were collected using a
      modified larval seine. Of these, 4391 were collected in the leeward and 1311 in
      the windward sector of the bay, representing a total of 23 families and 57
      species. Dominant fish families included Clinidae, Engraulidae, Kyphosidae,
      Mugilidae, Soleidae and Sparidae, similar to the situation elsewhere,
      highlighting continuity in the composition of larval fish assemblages and the
      utilization of surf zones by a specific group of larval fishes. Nineteen estuary
      associated marine species occurred within the surf zones of Algoa Bay and
      dominated catches (86.7%) in terms of abundance. Postflexion larvae comprised >
      80% of the catch, indicating the importance of the seemingly inhospitable surf
      zone environment for the early life stages of many fish species. The greatest
      species diversity was observed within the windward sector of the bay. Distance
      based linear modelling identified wave period as the environmental variable
      explaining the largest proportion of the significant variation in the larval fish
      assemblage. The physical disturbance generated by breaking waves could create a
      suitable environment for fish larvae, sheltered from predators and with an
      abundance of food resources. 

PMID- 24684378
TI  - An examination of the HIV serostatus disclosure process among Haitian immigrants
      in New York City.
AB  - Little is known about the HIV serostatus disclosure experience of Haitian
      immigrants in the USA. We employed the disclosure processes model to examine the
      disclosure experience of 21 HIV-positive Haitian immigrants in New York City.
      Data were collected through in-depth interviews conducted between May 2012 and
      January 2013 with participants from four community-based organizations providing
      HIV/AIDS services. Analysis of the interviews yielded several enablers relevant
      to reasons for disclosure including participants being in a close relationship
      with someone they trusted or felt comfortable with, and the need for support and
      understanding about the illness. Some of the barriers to HIV serostatus
      disclosure were fear of being stigmatized, rejected. For participants who had
      disclosed to significant others in the USA and in Haiti, they reported that they
      experienced both positive and negative outcomes including social support,
      emotional relief, encouragement to take their medication, and on some occasions
      mistreatments, isolation, and stigma. The strategies participants employed during
      the disclosure event also revealed the additional challenges immigrants face when
      deciding to disclose their HIV serostatus to family members living in their
      country of origin. These findings suggest the need to develop culturally
      appropriate interventions to address the disclosure needs of ethnic minorities
      residing in the USA.

PMID- 24684379
TI  - Gamma-glutamyltransferase predicts increased risk of mortality: a systematic
      review and meta-analysis of prospective observational studies.
AB  - The aim of this study was to evaluate the association between gamma
      glutamyltransferase (GGT) and mortality through a comprehensive analysis of
      existing evidence. PubMed, Embase, Chinese Biomedical Literature, and Science
      Citation Index databases were electronically searched. Studies were included if
      the study design was prospective and included reference and at-risk levels of GGT
      at baseline and mortality as a separate outcome. The quality of the studies
      included was assessed on the basis of Newcastle-Ottawa scale. Data from selected
      qualified studies were systematically reviewed, pooled, and analyzed according to
      the MOOSE guidelines and PRISMA statement. The results included the following: 1.
      35 studies including 571,511 participants and 72,196 cases of mortality; 2. GGT,
      even at physiologic levels, was associated with increased all-cause mortality and
      cardiovascular mortality, and might also be associated with cancer-related
      mortality in the general population; and 3. GGT was very likely to be associated
      with all-cause mortality and cardiovascular mortality in patients with coronary
      artery disease and type 2 diabetes mellitus. Many of the studies included did not
      specifically exclude subjects with hepatic diseases or alcohol abuse, which may
      have obscured the results. Moderate heterogeneity was observed in the meta
      analysis of GGT and all-cause mortality. Different compositions of cause-specific
      mortality might be the reason. However, subgroup analysis could only be performed
      on cardiovascular death because of insufficient information. GGT, even at
      physiologic high levels, predicted mortality, especially cardiovascular mortality
      and cancer mortality. The underlining mechanism and potential effects of GGT
      targeted intervention on health warrant further investigation.

PMID- 24684380
TI  - Immediate loading of implants installed in a healed alveolar bony ridge or
      immediately after tooth extraction: an experimental study in dogs.
AB  - OBJECTIVE: To compare the sequential healing at immediately loaded implants
      installed in a healed alveolar bony ridge or immediately after tooth extraction.
      MATERIAL AND METHODS: In the mandible of 12 dogs, the second premolars were
      extracted. After 3 months, the mesial roots of the third premolars were
      endodontically treated and the distal roots extracted. Implants were placed
      immediately into the extraction sockets (test) and in the second premolar region
      (control). Crowns were applied at the second and third maxillary premolars, and
      healing abutments of appropriate length were applied at both implants placed in
      the mandible and adapted to allow occlusal contacts with the crowns in the
      maxilla. The time of surgery and time of sacrifices were planned in such a way to
      obtain biopsies representing the healing after 1 and 2 weeks and 1 and 3 months.
      Ground sections were prepared for histological analyses. RESULTS: At the control
      sites, a resorption of the buccal bone of 1 mm was found after 1 week and
      remained stable thereafter. At the test sites, the resorption was 0.4 mm at 1
      week period and further loss was observed after 1 month. The height of the peri
      implant soft tissue was 3.8 mm both at test and control sites. Higher values of
      mineralized bone-to-implant contact and bone density were seen at the controls
      compared with the test sites. The differences, however, were not statistically
      significant. CONCLUSIONS: Different patterns of sequential early healing were
      found at implants installed in healed alveolar bone or in alveolar sockets
      immediately after tooth extractions. However, three months after implant
      installation, no statistically significant differences were found for the hard-
      and soft-tissue dimensions.

PMID- 24684382
TI  - Estrogen receptor mutations in breast cancer-an anticipated "rediscovery?".

PMID- 24684385
TI  - Mistaken conclusions in a nonmelanoma skin cancer article published in JAMA.

PMID- 24684381
TI  - Cysteine oxidation reactions catalyzed by a mononuclear non-heme iron enzyme
      (OvoA) in ovothiol biosynthesis.
AB  - OvoA in ovothiol biosynthesis is a mononuclear non-heme iron enzyme catalyzing
      the oxidative coupling between histidine and cysteine. It can also catalyze the
      oxidative coupling between hercynine and cysteine, yet with a different regio
      selectivity. Due to the potential application of this reaction for industrial
      ergothioneine production, in this study, we systematically characterized OvoA by
      a combination of three different assays. Our studies revealed that OvoA can also
      catalyze the oxidation of cysteine to either cysteine sulfinic acid or cystine.
      Remarkably, these OvoA-catalyzed reactions can be systematically modulated by a
      slight modification of one of its substrates, histidine. 

PMID- 24684384
TI  - Nutrition and brain development in early life.
AB  - Presented here is an overview of the pathway from early nutrient deficiency to
      long-term brain function, cognition, and productivity, focusing on research from
      low- and middle-income countries. Animal models have demonstrated the importance
      of adequate nutrition for the neurodevelopmental processes that occur rapidly
      during pregnancy and infancy, such as neuron proliferation and myelination.
      However, several factors influence whether nutrient deficiencies during this
      period cause permanent cognitive deficits in human populations, including the
      child's interaction with the environment, the timing and degree of nutrient
      deficiency, and the possibility of recovery. These factors should be taken into
      account in the design and interpretation of future research. Certain types of
      nutritional deficiency clearly impair brain development, including severe acute
      malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency.
      While strategies such as salt iodization and micronutrient powders have been
      shown to improve these conditions, direct evidence of their impact on brain
      development is scarce. Other strategies also require further research, including
      supplementation with iron and other micronutrients, essential fatty acids, and
      fortified food supplements during pregnancy and infancy. 

PMID- 24684386
TI  - Comparison of tissue Doppler imaging with MRI t2* and 24-hour rhythm holter heart
      rate variability for diagnosing early cardiac impairment in thalassemia major
      patients.
AB  - OBJECTIVES: Cardiology follow up is important in thalassemia major patients. The
      object of this study is to define parameters which can be used in the early
      detection of cardiac impairment. MATERIAL AND METHODS: Forty seven beta
      thalassemia major patients (mean age 16.3 +/- 4.47 years; 22 boys, 25 girls)
      whose left ventricular systolic functions were normal and a healthy control group
      of fifty age and gender matched children were included in the study. M-mode
      echocardiographic measurements, systolic and diastolic functions with PW and
      tissue Doppler and heart rate variabilities (HRVs) were compared between the two
      groups. The patients were also grouped according to MRT2*, ferritin and left
      ventricular diastolic diameters (LVDds) to compare the echocardiographic and
      Holter parameters among them. RESULTS: None of the children in the study group
      had symptomatic congestive heart failure. PW Doppler late diastolic forward flow
      in pulmonary artery was higher in the thalassemia group when compared with the
      control group (P = 0.01) indicating decreased compliance of the right ventricle.
      While the systolic and diastolic functions were normal, all the HRV parameters in
      the thalassemia group were significantly lower than the control group (P =
      0.005). CONCLUSIONS: Significant decrease in HRV and increase in PW late
      diastolic forward flow in pulmonary artery in the absence of systolic or
      diastolic dysfunction, points out that these parameters can be useful in
      detection of early cardiac impairment.

PMID- 24684387
TI  - Excited-state intramolecular hydrogen transfer (ESIHT) of 1,8-dihydroxy-9,10
      anthraquinone (DHAQ) characterized by ultrafast electronic and vibrational
      spectroscopy and computational modeling.
AB  - We combine ultrafast electronic and vibrational spectroscopy and computational
      modeling to investigate the photoinduced excited-state intramolecular hydrogen
      transfer dynamics in 1,8-dihydroxy-9,10-anthraquinone (DHAQ) in
      tetrachloroethene, acetonitrile, dimethyl sulfoxide, and methanol. We analyze the
      electronic excited states of DHAQ with various possible hydrogen-bonding schemes
      and provide a general description of the electronic excited-state dynamics based
      on a systematic analysis of femtosecond UV/vis and UV/IR pump-probe spectroscopic
      data. Upon photoabsorption at 400 nm, the S2 electronic excited state is
      initially populated, followed by a rapid equilibration within 150 fs through
      population transfer to the S1 state where DHAQ exhibits ESIHT dynamics. In this
      equilibration process, the excited-state population is distributed between the
      9,10-quinone (S2) and 1,10-quinone (S1) states while undergoing vibrational
      energy redistribution, vibrational cooling, and solvation dynamics on the 0.1-50
      ps time scale. Transient UV/vis pump-probe data in methanol also suggest
      additional relaxation dynamics on the subnanosecond time scale, which we
      tentatively ascribe to hydrogen bond dynamics of DHAQ with the protic solvent,
      affecting the equilibrium population dynamics within the S2 and S1 electronic
      excited states. Ultimately, the two excited singlet states decay with a solvent
      dependent time constant ranging from 139 to 210 ps. The concomitant electronic
      ground-state recovery is, however, only partial because a large fraction of the
      population relaxes to the first triplet state. From the similarity of the time
      scales involved, we conjecture that the solvent plays a crucial role in breaking
      the intramolecular hydrogen bond of DHAQ during the S2/S1 relaxation to either
      the ground or triplet state. 

PMID- 24684388
TI  - Mitochondrial pharmacology: energy, injury and beyond.
AB  - While the mitochondrion has long fascinated biologists and the sheer diversity of
      druggable targets has made it attractive for potential drug development, there
      has been little success translatable to the clinic. Given the diversity of inborn
      errors of metabolism and mitochondrial diseases, mitochondrially mediated
      oxidative stress (myopathies, reperfusion injury, Parkinson's disease, ageing)
      and the consequences of disturbed energetics (circulatory shock, diabetes,
      cancer), the potential for meaningful gain with novel drugs targeting
      mitochondrial mechanisms is huge both in terms of patient quality of life and
      health care costs. In this themed issue of the British Journal of Pharmacology,
      we highlight the key directions of the contemporary advances in the field of
      mitochondrial biology, emerging drug targets and new molecules which are close to
      clinical application. Authors' contributions are diverse both in terms of species
      and organs in which the mitochondrially related studies are performed, and from
      the perspectives of mechanisms under study. Defined roles of mitochondria in
      disease are updated and previously unknown contributions to disease are described
      in terms of the interface between basic science and pathological relevance.

PMID- 24684391
TI  - Equine orbital fractures: a review of 18 cases (2006-2013).
AB  - OBJECTIVE: To review the clinical features, treatments, complications, and
      outcomes of horses with traumatic orbital fractures. STUDY DESIGN: Retrospective
      study. SAMPLE POPULATION: Eighteen horses with confirmed orbital fractures.
      PROCEDURES: Medical records of horses presenting with orbital fractures between
      2006 and 2013 were reviewed. Signalment, etiology of fracture, clinical signs,
      fracture descriptions, diagnostic imaging, treatments, complications, and
      outcomes were evaluated. RESULTS: Eighteen horses presented with orbital
      fractures resulting from rearing in a confined space (n = 5), being kicked (4),
      colliding with a stationary object (3), and unknown trauma (6). Radiography and
      computed tomography were effective at classifying fractures and evaluating
      sinus/nasal involvement. Epistaxis/sinusitis were associated with fractures of
      the zygomatic process of the temporal bone (n = 3) and comminuted fractures of
      multiple bones (5). Seventeen fractures required treatment, with fifteen
      receiving a combination of medical and surgical therapy. Surgery included
      reduction of large bony fragments (n = 8), removal of small fragments (12),
      stabilization with a wire implant (1), and sinus trephination and lavage (5).
      Factors contributing to a favorable outcome included: globe retention (n = 16),
      vision (14), comfort (15), cosmesis (9), and return to previous function (13).
      CONCLUSIONS: Horses sustaining orbital fractures treated promptly with medical
      and surgical therapy have a favorable prognosis for return to function and
      cosmesis. Fractures affecting the zygomatic process of the frontal bone are
      unlikely to involve the sinus/nasal cavities. Epistaxis and sinusitis warrant
      more aggressive therapy and decrease functional and cosmetic outcome.

PMID- 24684390
TI  - A pilot study of plasma metabolomic patterns from patients treated with ketamine
      for bipolar depression: evidence for a response-related difference in
      mitochondrial networks.
AB  - BACKGROUND AND PURPOSE: (R,S)-ketamine produces rapid and significant
      antidepressant effects in approximately 65% of patients suffering from treatment
      resistant bipolar depression (BD). The genetic, pharmacological and biochemical
      differences between ketamine responders and non-responders have not been
      identified. The purpose of this study was to employ a metabolomics approach, a
      global, non-targeted determination of endogenous metabolic patterns, to identify
      potential markers of ketamine response and non-response. EXPERIMENTAL APPROACH:
      Plasma samples from 22 BD patients were analyzed to produce metabolomic patterns.
      The patients had received ketamine in a placebo-controlled crossover study and
      the samples were obtained 230 min post-administration at which time the patients
      were categorized as responders or non-responders. Matching plasma samples from
      the placebo arm of the study were also analysed. During the study, the patients
      were maintained on either lithium or valproate. KEY RESULTS: The metabolomic
      patterns were significantly different between the patients maintained on lithium
      and those maintained on valproate, irrespective of response to ketamine. In the
      patients maintained on lithium, 18 biomarkers were identified. In responders,
      lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased
      relative to non-responders. CONCLUSIONS AND IMPLICATIONS: The results indicate
      that the differences between patients who respond to ketamine and those who do
      not are due to alterations in the mitochondrial beta-oxidation of fatty acids.
      These differences were not produced by ketamine administration. The data indicate
      that pretreatment metabolomics screening may be a guide to the prediction of
      response and a potential approach to the individualization of ketamine therapy.

PMID- 24684392
TI  - Association of HMGB1 and HMGB2 genetic polymorphisms with lung cancer
      chemotherapy response.
AB  - The aim of the present study was to investigate the association of genetic
      polymorphisms in high mobility group box 1 and 2 (HMGB1 and HMGB2, respectively)
      with platinum-based chemotherapy responses in Chinese lung cancer patients. In
      total, 338 Chinese lung cancer patients (154 responders and 184 non-responders)
      were recruited to the study. All patients received at least two cycles of first
      line platinum-based chemotherapy. Three tagging single nucleotide polymorphisms
      (SNPs) of HMGB1 and two tagging SNPs of HMGB2 were detected in patients. We found
      that rs1412125 and rs2249825 of HMGB1 were significantly associated with the
      platinum-based chemotherapy response in both recessive and genotypic models. In
      addition, rs1412125 showed significant association with platinum-based
      chemotherapy response for the subgroup of patients aged >55 years in additive,
      recessive and genotypic models. No significant associations were detected between
      other SNPs and the platinum-based chemotherapy response. The HMGB1 SNPs
      (rs1412125 and rs2249825) were associated with platinum-based chemotherapy
      responses in Chinese lung cancer patients. In conclusion, HMGB1 SNPs may serve as
      potential biomarkers for predicting the efficacy of platinum-based chemotherapy. 

PMID- 24684393
TI  - Footprints of recent selection and variability in breed composition in the
      Gottingen Minipig genome.
AB  - The Gottingen Minipig (GMP) developed at the University of Gottingen is a
      synthetic breed that is widely used in medical research and toxicology. It
      combines the high fertility of the Vietnamese potbellied pig, the low body weight
      of the Minnesota Minipig and the white coat colour of the German Landrace pig.
      The aim of this study was to find genomic regions that may have undergone
      selection since the creation of the breed in the 1960s. Therefore, the whole
      genome was screened for footprints of recent selection based on single nucleotide
      polymorphism (SNP) genotypes from the Illumina Porcine SNP60 BeadChip using two
      methods: the extended haplotype homozygosity (EHH) test and the estimation of the
      genomic proportion of the three original breeds at each SNP using a Bayesian
      approach. Local deviations from the average genome-wide breed composition were
      tested with a permutation-based empirical test. Results for a comprehensive whole
      genome scan for both methods are presented. Several regions showing the highest P
      values in the EHH test are related to breeding goals relevant in the GMP, such as
      growth (SOCS2, TXN, DDR2 and GRB10 genes) and white colour (PRLR gene).
      Additionally, the calculated proportion of the founder breeds diverged
      significantly in many regions from the pedigree-based expectations and the genome
      average. The results provide a genome-wide map of selection signatures in the
      GMP, which leads to a better understanding of selection that took place over the
      last decades in GMP breed development.

PMID- 24684394
TI  - Low risk of late intracranial complications in mild traumatic brain injury
      patients using oral anticoagulation after an initial normal brain computed
      tomography scan: education instead of hospitalization.
AB  - BACKGROUND AND PURPOSE: Mild traumatic brain injury (mTBI) is a common
      neurological disorder. Whether oral anticoagulation (OAC) use is a risk factor
      for secondary deterioration in mTBI patients after a normal computed tomography
      (CT) scan is unclear. Therefore data were retrospectively collected on patients
      with mTBI who used OAC to determine the incidence of secondary clinical
      deterioration after an initial normal head CT scan. METHODS: This was a
      retrospective single-centre patient record study. All patients with an mTBI who
      presented at the emergency department between January 2007 and October 2011 were
      selected. Inclusion criteria were mTBI and at least 1 week of OAC use resulting
      in an international normalized radio > 1.1. CT scans were re-evaluated for this
      study. RESULTS: A total of 211 mTBI patients using OAC and with an initial CT
      scan without abnormalities were included in the analysis. In five patients a
      secondary deterioration was found. One patient developed a subdural hematoma
      after 15 h of clinical observation. The other four patients became symptomatic
      between 2 and 28 days after trauma. CONCLUSIONS: A low risk of secondary
      deterioration within 24 h in mTBI patients taking OAC with a normal first head CT
      scan was found. Our study does not support the recommendation of the current
      guidelines that these patients should be clinically observed for at least 24 h.
      The fact that in our series the majority of secondary deteriorations occurred
      between 2 and 28 days after trauma underscores the importance of patient
      instructions upon discharge from the hospital.

PMID- 24684389
TI  - Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities.
AB  - Cells die by a variety of mechanisms. Terminally differentiated cells such as
      neurones die in a variety of disorders, in part, via parthanatos, a process
      dependent on the activity of poly (ADP-ribose)-polymerase (PARP). Parthanatos
      does not require the mediation of caspases for its execution, but is clearly
      mechanistically dependent on the nuclear translocation of the mitochondrial
      associated apoptosis-inducing factor (AIF). The nuclear translocation of this
      otherwise beneficial mitochondrial protein, occasioned by poly (ADP-ribose) (PAR)
      produced through PARP overactivation, causes large-scale DNA fragmentation and
      chromatin condensation, leading to cell death. This review describes the
      multistep course of parthanatos and its dependence on PAR signalling and nuclear
      AIF translocation. The review also discusses potential targets in the parthanatos
      cascade as promising avenues for the development of novel, disease-modifying,
      therapeutic agents.

PMID- 24684395
TI  - Engineering a microvascular capillary bed in a tissue-like collagen construct.
AB  - Previous studies have shown that plastic compression (PC) of collagen gels allows
      a rapid and controlled fabrication of matrix- and cell-rich constructs in vitro
      that closely mimic the structure and characteristics of tissues in vivo.
      Microvascular endothelial cells, the major cell type making up the blood vessels
      in the body, were added to the PC collagen to determine whether cells attach,
      survive, grow, and express endothelial cell characteristics when seeded alone or
      in coculture with other cells. Endothelial cells seeded on the PC collagen
      containing human foreskin fibroblasts (HFF) or human osteoblasts (HOS) formed
      vessel-like structures over 3 weeks in culture without the addition of exogenous
      growth factors in the medium. In contrast, on the PC scaffolds without HFF or
      HOS, human dermal microvascular endothelial cells (HDMEC) exhibited a typical
      cobblestone morphology for 21 days under the same conditions. We propose that the
      coculture of primary endothelial cells with PC collagen constructs, containing a
      stromal cell population, is a valuable technique for in vitro modeling of
      proangiogenic responses toward such biomimetic constructs in vivo. A major
      observation in the cocultures was the absence of gel contraction, even after 3
      weeks of fibroblast culture. This collagen form could, for example, be of great
      value in tissue engineering of the skin, as contractures are both aesthetically
      and functionally disabling. 

PMID- 24684396
TI  - Melanoma incidence and Breslow tumour thickness development in the central Alpine
      region of South Tyrol from 1998 to 2012: a population-based study.
AB  - BACKGROUND: Cutaneous melanoma incidence is increasing worldwide, especially for
      in situ and thin (<1 mm) lesions, while thick (>=1 mm) lesions have been
      generally stable in many studies; although epidemiological data on melanoma is
      readily available, population-based studies, especially on mountain regions, are
      rare. OBJECTIVE: The aim of this study was to analyse cutaneous melanoma
      incidence and Breslow tumour thickness in the central Alpine mountain region of
      South Tyrol, northern Italy. METHODS: All newly diagnosed cutaneous in situ and
      invasive melanomas in the resident population from 1998 to 2012 were taken from
      the Pathology Unit, Bolzano Hospital and South Tyrol Cancer Registry. Incidence
      and Breslow tumour thickness were analyzed. Statistical analyses included Mann
      Whitney and Kruskal-Wallis tests. RESULTS: A total of 784 in situ melanomas and
      1663 invasive melanomas were collected. In situ melanomas showed the highest
      increase: European age-standardized incidence rose from 2.44 per 100,000
      inhabitants in 1998-2002 to 16.01 in 2008-2012. Invasive melanoma incidence
      increased from 12.69 in 1998-2002, to 22.88 in 2008-2012. The incidence rise was
      observed in thin melanomas (from 8.39 to 16.18) and in thick melanomas (from 4.30
      to 6.70). Breslow distribution revealed a median value of 0.62 mm (mean 1.34; SD
      2.24; range 0.09-30.0) and did not change significantly over time (P = 0.286).
      Higher Breslow values were observed at advanced age (P < 0.001), among males (P =
      0.017), in nodular melanomas (P < 0.001) and at higher Clark levels (P < 0.001).
      Significant differences were also found in urban hospitals compared to rural
      hospitals during the whole period (P = 0.004), but not in the last 5 years (P =
      0.053). CONCLUSION: Incidence of cutaneous melanoma is increasing in South Tyrol,
      especially for in situ and thin lesions, but also for thick lesions; no reduction
      in median tumour thickness is observed. Rural areas and elevated altitudes may
      contribute to this effect.

PMID- 24684397
TI  - Covalent binding of nanoliposomes to the surface of magnetotactic bacteria for
      the synthesis of self-propelled therapeutic agents.
AB  - The targeted and effective delivery of therapeutic agents remains an unmet goal
      in the field of controlled release systems. Magnetococcus marinus MC-1
      magnetotactic bacteria (MTB) are investigated as potential therapeutic carriers.
      By combining directional magnetotaxis-microaerophilic control of these self
      propelled agents, a larger amount of therapeutics can be delivered surpassing the
      diffusion limits of large drug molecules toward hard-to-treat hypoxic regions in
      solid tumors. The potential benefits of these carriers emphasize the need to
      develop an adequate method to attach therapeutic cargos, such as drug-loaded
      nanoliposomes, without substantially affecting the cell's ability to act as
      delivery agents. In this study, we report on a strategy for the attachment of
      liposomes to MTB (MTB-LP) through carbodiimide chemistry. The attachment
      efficacy, motility, and magnetic response of the MTB-LP were investigated.
      Results confirm that a substantial number of nanoliposomes (~70) are efficiently
      linked with MTB without compromising functionality and motility. Cytotoxicity
      assays using three different cell types (J774, NIH/3T3, and Colo205) reveal that
      liposomal attachments to MTB formulation improve the biocompatibility of MTB,
      whereas attachment does not interfere with liposomal uptake. 

PMID- 24684398
TI  - Social networks and mental health among people living with human immunodeficiency
      virus (HIV) in Johannesburg, South Africa.
AB  - People living with human immunodeficiency virus (PLHIV) in developing countries
      can live longer due to improved treatment access, and a deeper understanding of
      determinants of their quality of life is critical. This study assessed the link
      between social capital, operationally defined in terms of social networks (group
      based and personal social networks) and access to network resources (access to
      material and non-material resources and social support) and health-related
      quality of life (HRQoL) among 554 (55% female) adults on HIV treatment through
      South Africa's public health system. Female study participants were involved with
      more group-based social networks but had fewer personal social networks in
      comparison to males. Access to network resources was higher among females and
      those from larger households but lower among older study participants. Experience
      of social support significantly increased with household economic status and
      duration at current residence. Social capital indicators were unrelated to HIV
      disease status indicators, including duration since diagnosis, CD4 count and
      viral load. Only a minority (13%) of study participants took part in groups
      formed by and for predominantly PLHIV (HIV support groups), and participation in
      such groups was unrelated to their mental or physical health. Personal rather
      than group-linked social networks and access to network resources were
      significantly associated with mental but not physical health, after controlling
      for sociodemographic characteristics. The findings of limited participation in
      HIV support groups and that the participation in such groups was not
      significantly associated with physical or mental health may suggest efforts among
      PLHIV in South Africa to normalise HIV as a chronic illness through broad-based
      rather than HIV-status bounded social participation, as a strategy for deflecting
      stigma. Further research is required to examine the effects of HIV treatment on
      social networking and participation among PLHIV within both rural and other urban
      settings of South Africa.

PMID- 24684399
TI  - Investigation of interfacial adhesion between the top ends of carbon nanotubes.
AB  - Understanding the interfacial forces of carbon nanotubes (CNTs) is fundamental to
      the development of electromechanical systems based on the contact of CNTs.
      However, experimental studies on the adhesion properties between CNTs are scarce
      despite the remarkable contact quality of CNTs. Here, we present an experimental
      investigation of the adhesion between the top ends of aligned, self-adjusted CNTs
      using a CNT-integrated microelectromechanical actuator. The pull-out and pull-in
      behaviors of the contact as a function of the applied force by the actuator are
      precisely identified by measuring the contact resistance between the CNTs. The
      adhesion between the top ends of individual CNTs is extracted from the measured
      adhesive strength between the CNT arrays, and it agrees with the theoretical
      values of the van der Waals interactions. By exploiting the adhesion of the CNT
      to-CNT contact, a programmable and reliable microelectromechanical switching
      device is demonstrated. Our results offer design strategies for diverse CNT-based
      nano- and microelectromechanical devices that need repeatable contacting
      interfaces. 

PMID- 24684400
TI  - Facing warm temperatures during migration: cardiac mRNA responses of two adult
      Oncorhynchus nerka populations to warming and swimming challenges.
AB  - The main findings of the current study were that exposing adult sockeye salmon
      Onchorhynchus nerka to a warm temperature that they regularly encounter during
      their river migration induced a heat shock response at an mRNA level, and this
      response was exacerbated with forced swimming. Similar to the heat shock
      response, increased immune defence-related responses were also observed after
      warm temperature treatment and with a swimming challenge in two different
      populations (Chilko and Nechako), but with some important differences. Microarray
      analyses revealed that 347 genes were differentially expressed between the cold
      (12-13 degrees  C) and warm (18-19 degrees  C) treated fish, with stress response
      (GO:0006950) and response to fungus (GO:0009620) elevated with warm treatment,
      while expression for genes involved in oxidative phosphorylation (GO:0006119) and
      electron transport chain (GO:0022900) elevated for cold-treated fish. Analysis of
      single genes with real-time quantitative PCR revealed that temperature had the
      most significant effect on mRNA expression levels, with swimming and population
      having secondary influences. Warm temperature treatment for the Chilko population
      induced expression of heat shock protein (hsp) 90alpha, hsp90beta and hsp30 as
      well as interferon-inducible protein. The Nechako population, which is known to
      have a narrower thermal tolerance window than the Chilko population, showed even
      more pronounced stress responses to the warm treatment and there was significant
      interaction between population and temperature treatment for hsp90beta
      expression. Moreover, significant interactions were noted between temperature
      treatment and swimming challenge for hsp90alpha and hsp30, and while swimming
      challenge alone increased expression of these hsps, the expression levels were
      significantly elevated in warm-treated fish swum to exhaustion. In conclusion, it
      seems that adult O. nerka currently encounter conditions that induce several
      cellular defence mechanisms during their once-in-the-lifetime migration. As river
      temperatures continue to increase, it remains to be seen whether or not these
      cellular defences provide sufficient protection for all O. nerka populations. 

PMID- 24684401
TI  - Notable decrease of malignant pleural effusion after treatment with sorafenib in
      radioiodine-refractory follicular thyroid carcinoma.
AB  - BACKGROUND: Malignant pleural effusion (MPE) caused by metastatic differentiated
      thyroid carcinoma (DTC) is usually associated with a rapid fatal outcome and
      should be recognized as a grim prognostic indicator. A standard therapeutic
      strategy has not been established for this situation. Here, we report a
      radioiodine-refractory follicular thyroid carcinoma (FTC) patient in whom a
      notable decrease of MPE was achieved after treatment with sorafenib. PATIENT
      FINDINGS: A 50-year-old patient underwent a total thyroidectomy and resection of
      recurrence for poorly differentiated FTC followed by radioiodine therapy with a
      negative whole body scan. One year later, dissection of the inferior lobe of the
      left lung was performed because two fluorodeoxyglucose-avid nodules were
      identified; pathological examination revealed a metastatic poorly differentiated
      FTC. Half a year later, he was referred to our clinic because of cough, thoracic
      pain, nausea, and loss of appetite. Chest computed tomography showed right lung
      multiple nodules, left pleural effusion, and left lung collapse with left-sided
      pleural thickening. We treated him with sorafenib. Clinical and radiographic
      assessments were performed periodically. SUMMARY: Symptoms and signs improved
      dramatically and continuously after initiation of sorafenib treatment. A duration
      of more than 12 weeks of apparent reduction of pleural effusion was achieved,
      which was confirmed by consecutive computed tomography examinations. Despite
      grade 1 alopecia, no other obvious treatment-related adverse events occurred.
      CONCLUSIONS: As a grim prognostic indicator for patients with DTC, no standard
      treatment recommendation for pleural effusion exists. Targeted therapy using
      sorafenib may be an effective therapeutic strategy in the treatment of MPE caused
      by FTC.

PMID- 24684402
TI  - Gold(I)-catalyzed intra- and intermolecular alkenylations of beta-yne-pyrroles:
      facile formation of fused cycloheptapyrroles and functionalized pyrroles.
AB  - An efficient gold(I)-catalyzed alkenylation of beta-alkyne-substituted pyrroles
      is reported. The intramolecular reaction gives straightforward access to
      different types of seven-membered-ring-fused pyrroles with endo-selectivity, and
      the intermolecular reaction with alkynes provides functionalized pyrrole
      derivatives. 

PMID- 24684404
TI  - Publish only your original research.

PMID- 24684403
TI  - Adipocytokine expression associated with miRNA regulation and diagnosis of NASH
      in obese patients with NAFLD.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is strongly
      associated with visceral adiposity. The secretion of adipocytokines from white
      adipose tissue (WAT) promoting necroinflammation, and/or fibrosis may play
      important roles in the pathogenesis of non-alcoholic steatohepatits (NASH). In a
      previous study, reduced expression of a number of miRNA species in WAT
      concomitant with histological diagnosis of NASH was successfully demonstrated. In
      this study, we measure the expression of several predicted miRNA regulatory
      targets relevant to NAFLD and NASH including mTOR, FAS, IL20, SEMA4C, ADAMTS6 and
      IL13RA. We then examine hepatic receptor expression by immunohistochemical
      staining and qPCR. METHODS: White adipose tissue was collected from 24 obese
      patients undergoing bariatric surgery with biopsy-proven NAFLD. Extracted total
      RNAs from the adipose tissue were reverse transcribed and profiled for gene
      expression by qPCR for specific individual mRNA targets defined after
      identification by any two of three of the major prediction services: miRanda,
      TarBase or PicTar. All liver biopsies were read by a singly hepatopathologist.
      The same liver tissue was used to stain for hepatic receptor expression for FASLG
      and IL20. Additionally, the same tissue was used for qPCR for FASLG and IL20.
      RESULTS: Increases in the expression of IL13RA, mTOR, IL20, SEMA4C and FAS were
      detected and negatively correlated with putative regulatory miRNA. Hepatic
      receptor expression for FAS and IL20 was noted to correlate with markers of
      inflammation and severity of NAFLD. CONCLUSION: These data are consistent with
      the hypothesis that specific adipocytokines secreted by WAT will impact hepatic
      tissue and participate in the pathogenesis of NASH.

PMID- 24684405
TI  - Tinnitus pitch and minimum masking levels in different etiologies.
AB  - OBJECTIVE: We sought to determine whether the results of audiological tests and
      tinnitus characteristics, particularly tinnitus pitch and minimum masking level
      (MML), depend on tinnitus etiology, and what other etiology-specific tinnitus
      characteristics there are. DESIGN: The patients answered questions concerning
      tinnitus laterality, duration, character, aggravation, alleviation, previous
      treatment, and circumstances of onset. The results of tympanometry, pure-tone
      audiometry, distortion-product otoacoustic emissions, tinnitus likeness spectrum,
      MML, and uncomfortable loudness level were evaluated. STUDY SAMPLE: Patients with
      several tinnitus etiological factors were excluded. The remaining participants
      were divided into groups according to medical history: acute acoustic trauma: 67
      ears; chronic acoustic trauma: 82; prolonged use of oral estrogen and
      progesterone contraceptives: 46; Meniere's disease: 25; congenital hearing loss:
      19; sensorineural sudden deafness: 40; dull head trauma: 19; viral labyrinthitis:
      53; stroke: 6; presbycusis: 152. Data of 509 ears were analysed. RESULTS:
      Tinnitus pitch was highest in patients with acute acoustic trauma and lowest in
      patients receiving estrogen and progesterone. MML was lowest after acute acoustic
      trauma and in congenital hearing loss, and highest after a stroke and in the case
      of presbytinnitus. CONCLUSIONS: Tinnitus pitch and MML are etiology dependent.

PMID- 24684406
TI  - Ototoxicity effects of low exposure to solvent mixture among paint manufacturing
      workers.
AB  - OBJECTIVE: To evaluate auditory function in a group of workers exposed to organic
      solvent mixture at a paint factory. DESIGN: Cross-sectional study. STUDY SAMPLE:
      One hundred and sixty-one workers were studied, 77 exposed to solvents and 84
      unexposed. Fourteen solvents were measured, including toluene, xylene, and n
      hexane. Pure-tone audiometry and brainstem auditory-evoked potentials (BAEP) were
      performed. Industrial noise was < 85 dBA and exposure levels to organic solvents
      were low. RESULTS: The exposed group showed a hearing impairment in both ears
      compared with the unexposed workers. Multiple linear regression models adjusted
      by age, chronic pathologies, and environmental noise for frequency means between
      125 and 8000 Hz produced the following results: for the left ear, R(2) = 33.3%,
      exposed vs. unexposed beta = 4.1 (p < 0.001); and for the right ear, R(2) = 38%,
      exposed vs. unexposed beta = 4.8 (p < 0.001). Adjusted for age and chronic
      pathologies, waves III and V, and interpeak interval latencies were increased (p
      < 0.05) in both ears in the exposed group. CONCLUSIONS: Although solvent mixture
      concentrations and noise levels were low, our results demonstrate that there may
      be a concurrent ototoxicity and neurotoxicity condition and emphasize the
      importance of including BAEP analysis for comprehensive assessments. Future
      studies that include otoacoustic emissions assessments to monitor cochlear
      function and central auditory processing tests are imperative.

PMID- 24684407
TI  - Hepatic steatosis and non-alcoholic fatty liver disease are not associated with
      decline in renal function in people with Type 2 diabetes.
AB  - AIMS: We aimed to determine whether the presence of hepatic steatosis and/or non
      alcoholic fatty liver disease was associated with decline in renal function or
      onset of microalbuminuria in a cohort of people with Type 2 diabetes, including
      those managed in both primary and secondary care. METHODS: Nine hundred and
      thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of
      Scottish men and women aged 60-74 years with Type 2 diabetes, underwent
      assessment for hepatic steatosis by liver ultrasonography 1 year after
      recruitment. Non-alcoholic fatty liver disease was defined as the presence of
      steatosis following exclusion of secondary causes of liver disease. Patients were
      followed for 4 years and decline in renal function was assessed by the change in
      estimated glomerular filtration rate over time. RESULTS: Of the 933 subjects, 530
      had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic
      fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver
      disease were significantly associated with rate of decline in renal function,
      with the mean rate of decline in estimated glomerular filtration rate being -1.55
      ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared
      with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar
      results were obtained when the analysis was restricted to participants with and
      without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2)
      per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor
      non-alcoholic fatty liver disease were associated with the onset or regression of
      albuminuria during follow-up (all P >= 0.05). CONCLUSIONS: The presence of
      hepatic steatosis/non-alcoholic fatty liver disease was not associated with
      decline in renal function during a 4-year follow-up in our cohort of older people
      with Type 2 diabetes.

PMID- 24684408
TI  - Tocilizumab is clinically, functionally, and radiographically effective and safe
      either with or without low-dose methotrexate in active rheumatoid arthritis
      patients with inadequate responses to DMARDs and/or TNF inhibitors: a single
      center retrospective cohort study (KEIO-TCZ study) at week 52.
AB  - OBJECTIVES: To explore the effectiveness and safety of tocilizumab (TCZ) with or
      without methotrexate (MTX) in active rheumatoid arthritis (RA) patients showing
      inadequate responses to DMARDs and/or TNF inhibitors in clinical practice.
      METHODS: We observed consecutive 115 RA patients initiating TCZ treatment in Keio
      University Hospital, dividing them into two groups with (TCZ + MTX group) or
      without MTX (TCZ group), and evaluated clinical, functional and structural
      outcomes besides safety at week 52. RESULTS: Overall mean age, RA duration, and
      DAS28-ESR were 55.4, 8.4 years, and 5.0, respectively. Proportions of the prior
      use of TNF inhibitors and concomitant MTX were 45.5% and 57.4%, respectively.
      Mean dose of concomitant MTX was 8.4 mg/week. Baseline characteristics were
      comparable between the groups. TCZ improved disease activity measured by DAS28
      ESR to 2.1 at week 52 overall, without significant difference between the groups.
      Clinical (DAS28-ESR < 2.6), functional (HAQ-DI <= 0.5), and structural (DeltaTSS
      <= 0.5) remission rates in the TCZ group and the TCZ + MTX group were 79.1%/63.8%
      (P = 0.10), 62.8%/54.4% (P = 0.40), and 70.0%/53.8% (P = 0.61), respectively.
      Retention rates were 81.0% in the TCZ + MTX group and 88.5% in the TCZ group (P =
      0.47). The rate of serious adverse events was comparable between the groups.
      CONCLUSIONS: TCZ was clinically, functionally, and radiographically effective and
      safe either with or without low-dose MTX.

PMID- 24684409
TI  - Pulmonary and retroperitoneal lesions induced by methotrexate-associated
      lymphoproliferative disorder in a patient with rheumatoid arthritis.
AB  - A 78-year-old man had fatigue and appetite loss for 5 months. He had been
      receiving low-dose methotrexate for rheumatoid arthritis. Computed tomography
      revealed multiple pulmonary infiltrations and muddiness of the fatty tissue
      surrounding the right kidney, ureter wall thickening, and hydroureter/nephrosis,
      which were suspected retroperitoneal fibrosis. Lung biopsy revealed
      polymorphic/lymphoplasmacytic lymphoproliferative disorder. Methotrexate
      withdrawal resulted in spontaneous regression. Therefore, retroperitoneal lesion
      may account for the diagnosis as having retroperitoneal lymphoproliferative
      disorder, not retroperitoneal fibrosis. 

PMID- 24684410
TI  - Emergency water treatment with bleach in the United States: the need to revise
      EPA recommendations.
AB  - During emergencies in the United States, the Environmental Protection Agency
      (EPA) currently recommends using bottled water, or boiling or treating water by
      adding 1/8 teaspoon (or 8 drops) of bleach to 1 gal of water. This bleach
      recommendation is internally inconsistent, a relatively high chlorine dose (5.55
      8.67 mg/L), and unsupported by evidence. In this study, bleach was added in three
      different dosages to six waters available to emergency-affected populations in
      each of six states; free chlorine residual (FCR) and Escherichia coli/total
      coliforms were measured 1-24 h after treatment. Data were analyzed using four
      efficacy criteria. Results indicated the dosages in the current EPA
      recommendation are unnecessarily high to ensure (1) maintenance of FCR for 24 h
      after treatment, (2) absence of E. coli/total coliforms, and (3) establishment of
      a CT-factor sufficient to inactivate Giardia lamblia and enteric viruses 1 h
      after treatment. Additionally, emergency-prone populations did not have the
      materials to complete treatment with bleach in their household. Therefore, we
      recommend EPA review and revise the current recommendation to establish an
      internally consistent, criteria-based recommendation that is usable by emergency
      affected populations. We also recommend investigating the use of new or
      commercially available water treatment products for emergency response in the
      United States.

PMID- 24684411
TI  - Healing of implants installed in over- or under-prepared sites--an experimental
      study in dogs.
AB  - OBJECTIVE: To study bone healing at implants installed with different insertion
      torques. MATERIAL AND METHODS: In six Labrador dogs, all mandibular premolars and
      first molars were extracted. After 4 months of healing, flaps were elevated, and
      two implant sites were prepared at each side of the mandible. In the right side
      of the mandible, the distal sites were prepared conventionally, while the mesial
      sites were over-prepared by 0.2 mm. As a consequence, a final insertion torque of
      ~30 Ncm at the distal and a minimal insertion torque close to 0 Ncm at the mesial
      sites were obtained. In the left sides of the mandible, however, the recipient
      sites were underprepared by 0.3 mm resulting in an insertion torque of >= 70 Ncm
      at both implants. Cover screws were applied, and flaps sutured to fully submerge
      the experimental sites. After 4 months, the animals were sacrificed and ground
      sections obtained for histological evaluation. RESULTS: The mineralized bone-to
      implant contact was in the range of 55.2-62.1%, displaying the highest value at
      implants with ~30 Ncm insertion torque and the lowest value at the implant sites
      with close to 0 Ncm insertion torque. No statistically significant differences
      were revealed. Bone density was in the range of 43.4-54.9%, yielding the highest
      value at implants with >= 70 Ncm insertion torque and the lowest at the implant
      sites with close to 0 Ncm insertion torque. The difference between the sites of
      ~30 Ncm and the corresponding >= 70 Ncm insertion torque reached statistical
      significance. CONCLUSIONS: Similar amounts of osseointegration were obtained
      irrespective of the insertion torque applied. Moreover, implants installed in
      sites with close to 0 Ncm insertion torque may properly osseointegrate as well.

PMID- 24684413
TI  - Pediatric subcutaneous panniculitis-like T-cell lymphoma with favorable result by
      immunosuppressive therapy: a report of two cases.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare type of skin
      lymphoma. Histopathology mimicking a lobular panniculitis makes it difficult to
      distinguish SPTL from benign autoimmune disease. We present cases of a 10-year
      old female and an 11-year-old male with SPTL showing recurrent panniculitis and
      systemic manifestations. Initially, antibiotics and steroids were administered to
      treat infectious disease and benign panniculitis. However, they experienced
      recurrent fever and erythema nodosum. Additional immunohistochemistry and T-cell
      receptor (TCR) gene rearrangement analyses were performed, enabling the
      establishment of an SPTL diagnosis. The affected patients were given
      immunosuppressive therapy with favorable results. 

PMID- 24684414
TI  - NICE guidelines on Prostate Cancer Active Surveillance: is UK practice leading
      the world?

PMID- 24684412
TI  - Novel roles of holocarboxylase synthetase in gene regulation and intermediary
      metabolism.
AB  - The role of holocarboxylase synthetase (HLCS) in catalyzing the covalent binding
      of biotin to the five biotin-dependent carboxylases in humans is well
      established, as are the essential roles of these carboxylases in the metabolism
      of fatty acids, the catabolism of leucine, and gluconeogenesis. This review
      examines recent discoveries regarding the roles of HLCS in assembling a
      multiprotein gene repression complex in chromatin. In addition, emerging evidence
      suggests that the number of biotinylated proteins is far larger than previously
      assumed and includes members of the heat-shock superfamily of proteins and
      proteins coded by the ENO1 gene. Evidence is presented linking biotinylation of
      heat-shock proteins HSP60 and HSP72 with redox biology and immune function,
      respectively, and biotinylation of the two ENO1 gene products MBP-1 and ENO1 with
      tumor suppression and glycolysis, respectively.

PMID- 24684415
TI  - Excitation of biomolecules with incoherent light: quantum yield for the
      photoisomerization of model retinal.
AB  - Cis-trans isomerization in retinal, the first step in vision, is often
      computationally studied from a time-dependent viewpoint. Motivation for such
      studies lies in coherent pulsed laser experiments that explore the isomerization
      dynamics. However, such biological processes take place naturally in the presence
      of incoherent light, which is expected to excite a nonevolving mixture of
      stationary states. Here the isomerization problem is considered from the latter
      viewpoint and applied to a standard two-state, two-mode linear vibronic coupling
      model of retinal that explicitly includes a conical intersection between the
      ground and first excited electronic states. The calculated quantum yield at 500
      nm agrees well with both the previous time-dependent calculations of Hahn and
      Stock (0.63) [ J. Phys. Chem. B 2000, 104, 1146-1149 ] and with experiment (0.65
      +/- 0.01), as does its wavelength dependence. Significantly, the effects of
      environmental relaxation on the quantum yield in this well-established model are
      found to be negligible. The results make clear the connection of the
      photoisomerization quantum yield to properties of stationary eigenstates,
      providing alternate insights into conditions for yield optimization. 

PMID- 24684416
TI  - A measure of chronic quality of life predicts socioeconomic and medical outcomes
      in psoriasis patients.
AB  - BACKGROUND: Psoriasis is a chronic skin disorder that detracts from quality of
      life, including elements of physical, psychological and social functioning.
      OBJECTIVE: This study investigated whether retrospective questions about chronic
      quality of life (CQoL) were better predictors of poor socioeconomic and medical
      outcomes than the current Dermatology Life Quality Index (DLQI). METHODS: One
      hundred fourteen participants answered the 10 questions used in the standard DLQI
      for 'over the last week', 'over the last year' and 'over your lifetime with
      psoriasis'. Subjects were examined and completed a self-administered
      questionnaire regarding disabilities, relationships, education and medical and
      economic outcomes (a smaller subset of 58 subjects also answered questions
      regarding religion and discrimination). RESULTS: Greater lifetime DLQI (LT DLQI)
      correlated with lower satisfaction with treatment (P = 0.007), greater concern
      that psoriasis will worsen (P = 0.012), worse perceived general health (P =
      0.003), younger age at which weight became problematic (P = 0.002), greater
      likelihood of believing psoriasis had caused weight gain (P < 0.001), shorter
      retention of current job (P = 0.001), more experiences of discrimination at work
      (P = 0.002) and in social settings (P < 0.001) over one's lifetime and more
      severe discrimination in social settings over one's lifetime (P = 0.002). Greater
      LT DLQI predicted more packs smoked per day (P = 0.005), greater likelihood of
      believing psoriasis caused smoking (P = 0.012), greater likelihood of
      recreational drug use (P = 0.004), greater likelihood of a depression diagnosis
      (P < 0.001), greater likelihood of having felt depressed (P = 0.011) and greater
      likelihood of believing psoriasis caused depression (P < 0.001). CONCLUSION:
      Compared to the standard LW DLQI, LT DLQI was a better predictor of patient
      outcomes related to weight, discrimination and depression.

PMID- 24684417
TI  - Evaluation of nerves in Mohs micrographic surgery: histologic mimickers of
      perineural invasion and nervous tissue on frozen section.
AB  - BACKGROUND: Perineural invasion (PNI) is an important histologic finding and may
      be a negative prognostic factor for squamous cell carcinoma (SCC). It may be
      associated with more-aggressive tumor behavior. Mohs surgeons encounter
      microscopic PNI regularly and must be able to diagnose it accurately to guide
      care decisions. OBJECTIVE: To describe benign histologic mimickers of PNI and
      neural structures in SCC commonly encountered on frozen, hematoxylin and eosin
      stained sections and to review how to differentiate them from PNI. METHODS AND
      MATERIALS: Review of the literature regarding histologic mimickers of PNI and
      additional contributions to frozen section PNI and nerve tissue mimickers.
      RESULTS: We describe benign findings, including arrector pili muscles, eccrine
      muscles, vessels, granulomatous inflammation, and eddies of SCC, that may each be
      mistaken for nerves or PNI. We discuss the ways in which they may be
      distinguished on frozen sections and review other commonly encountered entities
      that resemble PNI. CONCLUSION: Perineural inflammation and peritumoral fibrosis
      are common mimickers of PNI on frozen section, although other mimickers exist on
      permanent sections. Normal structures may appear "neural" by way of frozen tissue
      orientation, processing, or inflammation and thus must be differentiated from
      nerve tissue and PNI during Mohs surgery.

PMID- 24684418
TI  - Oestrogen upregulates the sarcoplasmic reticulum Ca(2+) ATPase pump in coronary
      arteries.
AB  - The presence of circulating plasma 17beta-oestradiol (E2) is beneficial in women
      against abnormal vascular tone development, such as coronary arterial vasospasms.
      Several vascular diseases have demonstrated that increased expression of the
      sarcoplasmic reticulum Ca(2+) -ATPase pump (SERCA2b) serves to limit the
      excessive accumulation of intracellular Ca(2+) . Therefore, the hypothesis of the
      present study was that E2 would increase SERCA2b expression in the coronary
      vasculature. Coronary arteries were dissected from hearts obtained from mature
      female pigs. Artery segments were cultured for 24 h in E2 (1 pmol/L or 1 nmol/L)
      and homogenized for western blot analysis. At 1 nmol/L, E2 induced an approximate
      50% increase in immunoreactivity for SERCA2b. In addition, E2 increased the
      protein expression of the known SERCA regulatory proteins, protein kinase A (PKA)
      and protein kinase G (PKG). The E2-induced increase in SERCA2b was attenuated
      when the culture medium was supplemented with the oestrogen receptor (ER)
      alpha/beta antagonist ICI 182,780 and the PKG antagonist KT5823 (10 MUmol/L, 24 h
      for both). The PKA antagonist (KT5720; 10 MUmol/L, 24 h) had no effect on SERCA2b
      expression. Removal of the endothelium (using a wooden toothpick) from artery
      segments prior to culture decreased the E2-mediated increase in SERCA2b and PKG
      expression by 45% and 47%, respectively. Overall, the findings suggest that one
      of the potential cardiovascular benefits of E2 in women is upregulation of
      SERCA2b, via activation of the classic ERalpha and ERbeta pathway. 

PMID- 24684420
TI  - Response of primary vectors and related diseases to impoundment by the Three
      Gorges Dam.
AB  - OBJECTIVES: To investigate the impact of the Three Gorges Dam on the local
      ecological environment. We conducted a 3-year cross-sectional survey of natural
      focus infectious diseases in the area before and after the water level rose to
      156 m to evaluate the dam's health impacts. METHODS: Direct and indirect
      immunofluorescence methods were applied to detect rat antigen and antibody of
      haemorrhagic fever with renal syndrome (HFRS). Fresh rat kidneys were inoculated
      in Korth's culture medium to detect Leptospira. A group of captured crabs were
      ground to observe the metacercariae of Paragonimus. Serum samples were collected
      from healthy local individuals. ELISA kits were used to detect human antibody
      against HFRS and paragonimiasis. Human Leptospira infections were detected by a
      microscopic agglutination test. RESULTS: Upstream rodent density increased
      significantly with Rattus flavipectus and Apodemus agrarius as the major
      pathophoric genera. The infection rate of human HFRS and Leptospira in the
      upstream human population samples was significantly higher than in the downstream
      samples and correlated with the increase in rodent density. Paragonimus infection
      rates remained at a low level during the study. Culex pipiens fatigan and
      Armigeres obturbans were the dominant species of mosquito. CONCLUSIONS: The
      creation of the Three Gorges Dam changed the proliferation of intermediary agents
      of diseases, but not notably. However, the ecological effects on the environment
      may require a prolonged period of time to manifest themselves; thus, long-term
      and effective surveillance of vectors and related diseases needs to be
      established.

PMID- 24684421
TI  - Endoscopic thyroidectomy is safe in patients with a high body mass index.
AB  - BACKGROUND: Obesity is associated with a number of medical comorbidities and is
      considered a risk factor for surgical complications. However, the impact of
      obesity on the safety of minimally invasive video-assisted thyroidectomy (MIVAT)
      has not been well defined. We sought to determine the relationship between
      obesity and the risk of complications in patients undergoing MIVAT. METHOD: A
      prospectively maintained database of all thyroid surgeries performed from January
      2006 through June 2012 was searched and all cases of MIVAT were identified.
      Patients were stratified into three body mass index (BMI) groups according to the
      National Institutes of Health classification for obesity: normal (BMI <= 24.9
      kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) and obese (BMI >= 30 kg/m(2)). The
      total number of complications was compared among the three groups, and MIVAT
      patients were also compared to a cohort of patients undergoing conventional
      thyroid surgery. RESULTS: There were 233 MIVATs performed on 223 patients. The
      mean overall BMI for the study population was 25.4 kg/m(2). There were 123
      procedures (52.8%) in the normal group, 76 procedures (32.6%) in the overweight
      group, and 34 procedures (14.6%) in the obese group. Complications included 1
      case of cellulitis (0.4%), 6 cases of temporary hypocalcemia (2.6%), and 6 cases
      of transient vocal fold paresis (2.6%). No patients suffered permanent
      hypocalcemia or a permanent recurrent laryngeal nerve injury. There were 9
      complications in the normal group (7.3%), 4 complications in the overweight group
      (5.3%), and no complications in the obese group. Due to the low number of
      complications in this series, the overweight and obese groups were combined into
      a high BMI group for further analysis. Statistical analysis using simple logistic
      regression models revealed that there was no significant difference in the number
      of complications in patients with a high BMI compared with patients with a normal
      BMI (odds ratio [OR] 0.48 [confidence interval (CI) 0.14-1.63], p=0.2). The MIVAT
      group had fewer overall complications than the conventional thyroidectomy group.
      CONCLUSIONS: Overweight and obese patients undergoing MIVAT in this series were
      not at an increased risk for surgical complications. The MIVAT procedure may be
      considered safe in patients with a high BMI, who may derive particular benefit
      from a minimally invasive approach.

PMID- 24684422
TI  - The benzoyl peroxide promoted dual C-C bond formation via dual C-H bond cleavage:
      alpha-phenanthridinylation of ether by isocyanide.
AB  - The benzoyl peroxide-promoted alpha-phenanthridinylation of ether by isocyanide
      is developed, proceeding through dual C-H bond cleavage and dual C-C bond
      formation. The procedure tolerates a series of functional groups, such as methyl,
      fluoro, chloro, acetyl, methoxy carbonyl, cyano, and trifluoromethyl. Thus, it
      represents a facile pathway leading to 6-substituted phenanthridine derivatives.
      The addition of radical to the isonitrile followed by a radical aromatic
      cyclization is involved in this transformation. 

PMID- 24684423
TI  - Highly flexible and tough concentric triaxial polystyrene fibers.
AB  - A combination of appropriate reinforcing material and morphology led to the
      highly tough, flexible, and strong polystyrene fibers by electrospinning.
      Concentric fiber morphology with reinforcing elastomeric thermoplastic
      polyurethane (TPU) sandwiched between the two layers of polystyrene made by a
      special nozzle (triaxial) showed toughness of >270 J g(-1) and 300% elongation
      without any cracks in comparison to toughness of <0.5 J g(-1) and elongation at
      break of <5% of polystyrene single fibers. The concentric triaxial morphology
      showed great advantage in comparison to the coaxial structure. Toughness and
      elongation at break were 1376 and 628% higher, respectively, for triaxial
      morphology in comparison to the coaxial fibers because of the better interface
      from the sandwich structure. 

PMID- 24684424
TI  - In this issue. Falling abortion rates, contraception and young adult sexual
      behavior.

PMID- 24684433
TI  - Radiocaesium concentrations in the muscle and eggs of salmonids from Lake
      Chuzenji, Japan, after the Fukushima fallout.
AB  - Approximately 18 months (September to December 2012) after the Fukushima Dai-ichi
      Nuclear Power Plant accident, elevated radiocaesium concentrations were measured
      in samples of muscle and eggs from masu salmon Oncorhynchus masou, kokanee
      Oncorhynchus nerka, brown trout Salmo trutta and lake trout Salvelinus namaycush
      from the Lake Chuzenji system, central Honshu Island, Japan (160 km from the
      station). Mean muscle concentrations were 142.9-249.2 Bq kg-1 wet mass and mean
      concentrations in eggs were 38.7-79.0 Bq kg-1 wet mass. There was no relationship
      between fork length and muscle radiocaesium concentration in any of the species,
      but there were significant relationships between individual muscle and egg
      radiocaesium concentrations from O. masou, S. trutta and S. namaycush.

PMID- 24684434
TI  - Postgrowth tuning of the bandgap of single-layer molybdenum disulfide films by
      sulfur/selenium exchange.
AB  - We demonstrate bandgap tuning of a single-layer MoS2 film on SiO2/Si via
      substitution of its sulfur atoms by selenium through a process of gentle
      sputtering, exposure to a selenium precursor, and annealing. We characterize the
      substitution process both for S/S and S/Se replacement. Photoluminescence and, in
      the latter case, X-ray photoelectron spectroscopy provide direct evidence of
      optical band gap shift and selenium incorporation, respectively. We discuss our
      experimental observations, including the limit of the achievable bandgap shift,
      in terms of the role of stress in the film as elucidated by computational
      studies, based on density functional theory. The resultant films are stable in
      vacuum, but deteriorate under optical excitation in air. 

PMID- 24684436
TI  - Multiple phytohormones and phytoalexins are involved in disease resistance to
      Magnaporthe oryzae invaded from roots in rice.
AB  - Blast, caused by the fungus Magnaporthe oryzae, is one of the most devastating
      diseases of rice worldwide. Phenylalanine ammonia lyase (PAL) is a key enzyme in
      the phenylpropanoid pathway, which leads to the biosynthesis of defense-related
      phytohormone salicylic acid (SA) and flavonoid-type phytoalexins sakuranetin and
      naringenin. However, the roles and biochemical features of individual rice PALs
      in defense responses to pathogens remain unclear. Here, we report that rice
      OsPAL06, which can catalyze the formation of trans-cinnamate using l
      phenylalanine, is involved in rice root-M. oryzae interaction. OsPAL06-knockout
      mutant showed increased susceptibility to M. oryzae invaded from roots and
      developed typical leaf blast symptoms, accompanied by nearly complete
      disappearance of sakuranetin and naringenin and a two-third reduction of the SA
      level in roots. This mutant also showed compensatively induced expression of
      chalcone synthase, which is involved in flavonoid biosynthesis, isochorismate
      synthase 1, which is putatively involved in SA synthesis via another pathway,
      reduced jasmonate content and increased ethylene content. These results suggest
      that OsPAL06 is a positive regulator in preventing M. oryzae infection from
      roots. It may regulate defense by promoting both phytoalexin accumulation and SA
      signaling that synergistically and antagonistically interacts with jasmonate- and
      ethylene-dependent signaling, respectively. 

PMID- 24684435
TI  - Severe 25-hydroxyvitamin D deficiency identifies a poor prognosis in patients
      with hepatocellular carcinoma - a prospective cohort study.
AB  - BACKGROUND: Vitamin D is involved in many biological processes. The role of
      vitamin D in patients with hepatocellular carcinoma (HCC) remains inconclusive,
      although there is evolving evidence that vitamin D may modulate cancer
      development and progression. AIM: To evaluate serum vitamin D as prognostic
      parameter in HCC, we performed a prospective cohort study. METHODS: HCC patients
      were prospectively recruited and 25-hydroxyvitamin D3 (25(OH)D3 ) levels were
      determined. 25(OH)D3 levels were compared to stages of cirrhosis and HCC stages
      with nonparametric Kruskal-Wallis tests and Spearman correlations in 200 HCC
      patients. The association of the 25(OH)D3 levels and overall survival (OS) was
      assessed in uni- and multivariate Cox regression models. RESULTS: Two-hundred
      patients with HCC were included. The mean follow-up time was 322 +/- 342 days
      with a range of 1-1508 days. Nineteen patients underwent liver transplantation
      and 60 patients died within the observation time. The mean serum 25(OH)D3
      concentration was 17 +/- 13 ng/mL with a range of 1-72 ng/mL. 25(OH)D3 serum
      levels negatively correlated with the stage of cirrhosis as well as with stages
      of HCC. Patients with severe 25(OH)D3 deficiency had the highest mortality risk
      (hazard ratio 2.225, 95% confidence interval 1.331-3.719, P = 0.002).
      Furthermore, very low 25(OH)D3 levels were associated with mortality
      independently from the MELD score and high alpha-Fetoprotein levels (>400 ng/mL)
      in a multivariate Cox regression model. CONCLUSIONS: We conclude that 25(OH)D3
      deficiency is associated with advanced stages of hepatocellular carcinoma and it
      is a prognostic indicator for a poor outcome.

PMID- 24684437
TI  - Dynamic hypoxia in scar tissue during human hypertrophic scar progression.
AB  - BACKGROUND: The skin color of human hypertrophic scar changes dynamically during
      scar progression. OBJECTIVE: To investigate whether hypoxia is dynamic during
      scar progression. METHODS: Thirty-five patients with early, proliferative,
      regressive, and mature scars were involved in this study. Tissue oxygen tension
      was measured before scar surgery. After surgery, the scar stage was further
      defined using hematoxylin and eosin staining, and microvessel density and hypoxia
      inducible factor-1 (HIF-1) expression were detected using immunohistochemistry to
      determine a correlation with oxygen level. RESULTS: Mild hypoxia is present in
      early scars, moderate hypoxia in proliferative scars, and severe hypoxia in
      regressive scars. Oxygen levels then return to normal in mature scars, which was
      consistent with the dynamic change in microvessel density. Meanwhile, HIF-1
      expression also changed dynamically along with alteration in oxygen levels.
      CONCLUSION: Hypoxia is dynamic in scar tissue and is possibly correlated with
      scar formation and regression.

PMID- 24684438
TI  - Peri-implant evaluation in type 2 diabetes mellitus patients: a 3-year study.
AB  - OBJECTIVE: The aim of this study was to analyze the changes produced in peri
      implant tissues in type 2 diabetes mellitus patients with different glycemia
      levels, measured by monitoring glycated hemoglobin A1c (HbA1c), over a period of
      3 years following dental implant placement. MATERIALS AND METHODS: Sixty-seven
      patients were divided into four groups according to their HbA1c levels: 21
      patients in Group 1 (<6); 24 patients in Group 2 (6.1-8); and 11 patients in
      Group 3 (8.1-10) and Group 4 (>10.1). Each patient received one implant. All
      implants were placed in the anterior zone of the maxilla. The variables selected
      to assess the general state of patients' peri-implant health were as follows:
      probing depth, bleeding on probing, and marginal bone loss. RESULTS: Marginal
      bone loss was found to increase in relation to increases in HbA1c levels.
      Bleeding on probing showed statistically significant differences between groups.
      When the peri-implant area was probed, mean levels of bleeding varied from 0.43
      in Group 1 at 1 year after implant surgery to 0.62 in Group 4 (P = 0.042 between
      the four study groups). After the second year, greater bleeding on probing was
      observed in Group 4 (0.63) in comparison with groups with lower HbA1c levels.
      Peri-implant pocket depths presented values that were too low to be considered
      pathological and without statistically significant differences between the study
      groups. CONCLUSION: Implant therapies for diabetic patients can be predictable,
      providing these patients fall within controlled ranges of glycemia over time,
      assessed by monitoring HbA1c levels.

PMID- 24684439
TI  - Global metabolite profiling reveals transformation pathways and novel metabolomic
      responses in Solea senegalensis after exposure to a non-ionic surfactant.
AB  - Alcohol polyethoxylate (AEO) surfactants are widely used in household and
      industrial products, but the health effects arising from short-term exposure to
      sublethal concentrations are unknown. A metabolomic approach was used to
      investigate the biotransformation and effects of exposure to sublethal
      concentrations of hexaethylene glycol monododecylether (C12EO6) in juvenile sole,
      Solea senegalensis. After 5 days, C12EO6 was rapidly metabolized in the sole by
      oxidation, glucuronidation, and ethoxylate chain shortening. C12EO6 exposure at
      either 146 or 553 MUg L(-1) resulted in significant metabolite disruption in
      liver and blood samples, including an apparent fold increase of >10(6) in the
      circulating levels of C24 bile acids and C27 bile alcohols, disturbance of
      glucocorticoid and lipid metabolism, and a 470-fold decrease in levels of the
      fatty acid transport molecule palmitoyl carnitine. Depuration resulted in rapid
      elimination of the surfactant and normalization of metabolites toward pre
      exposure levels. Our findings show for the first time the ability of metabolomic
      analyses to discern effects of this AEO on metabolite homeostasis at exposure
      levels below its no effect concentrations for survival and reproduction in
      juvenile fish. The pronounced alteration in levels of liver metabolites,
      phospholipids, and glucocorticoids in S. senegalensis in response to surfactant
      exposure may indicate that this contaminant could potentially impact a number of
      health end points in fish. 

PMID- 24684440
TI  - Levuglandin forms adducts with histone h4 in a cyclooxygenase-2-dependent manner,
      altering its interaction with DNA.
AB  - Inflammation and subsequent cyclooxygenase-2 (COX-2) activity has long been
      linked with the development of cancer, although little is known about any
      epigenetic effects of COX-2. A product of COX-2 activation, levuglandin (LG)
      quickly forms covalent bonds with nearby primary amines, such as those in lysine,
      which leads to LG-protein adducts. Here, we demonstrate that COX-2 activity
      causes LG-histone adducts in cultured cells and liver tissue, detectable through
      LC-MS, with the highest incidence in histone H4. Adduction is blocked by a gamma
      ketoaldehyde scavenger, which has no effect on COX-2 activity as measured by PGE2
      production. Formation of the LG-histone adduct is associated with an increased
      histone solubility in NaCl, indicating destabilization of the nucleosome
      structure; this is also reversed with scavenger treatment. These data demonstrate
      that COX-2 activity can cause histone adduction and loosening of the nucleosome
      complex, which could lead to altered transcription and contribute to
      carcinogenesis. 

PMID- 24684442
TI  - Age- and sex-related differences in sudomotor function evaluated by the
      quantitative sudomotor axon reflex test (QSART) in healthy humans.
AB  - The aim of the present study was to quantitatively investigate the age and sex
      related differences in sudomotor function in healthy humans. The quantitative
      sudomotor axon reflex test (QSART) with iontophoresis (2 mA for 5 min) and 10%
      acetylcholine (ACh) was performed to determine axon reflex-mediated (AXR), with
      and without iotophoresis (AXR(1) and AXR(2), respectively), and directly
      activated (DIR) sweating. All experiments were conducted under thermoneutral
      conditions (temperature 24.0 +/- 0.5 degrees C; relative humidity 40 +/- 3%). In
      general, men had enhanced values of onset time of AXR, sweat rates, activated
      sweat gland density (SGD) and activated sweat gland output (SGO) than women, but
      not in all cases. The onset time of AXR (r(2)  = 0.567; P < 0.001) was positively
      correlated with advancing age, whereas sweat rates of AXR(1) and AXR(2) (r(2)  =
      0.571 and r(2)  = 0.486, respectively; P < 0.0001), DIR (r(2)  = 0.594; P <
      0.0001), SGD (r(2)  = 0.496; P < 0.0001) and SGO (r(2)  = 0.551; P < 0.0001) were
      negatively correlated in both men and women with advancing age. The results
      demonstrate that an attenuation of sudomotor function occurs with aging in both
      sexes. Moreover, the findings showed a progressive increase in onset time and a
      decrease in sweat rates, SGD and SGO with increasing age in both sexes. A
      variation in sweat function was found between sexes, but not in all age groups. 

PMID- 24684441
TI  - Nuclear factor kappaB inhibition reduces lung vascular lumen obliteration in
      severe pulmonary hypertension in rats.
AB  - NF-kappaB and IL-6, a NF-kappaB downstream mediator, play a central role in the
      inflammatory response of tissues. We aimed to determine the role of the classical
      NF-kappaB pathway in severe pulmonary arterial hypertension (PAH) induced by
      SU5416 and chronic hypoxia (SuHx) in rats. Tissue samples from patients with
      idiopathic PAH (iPAH) and control subjects were investigated. SuHx rats were
      treated from Days 1 to 3, 1 to 21, and 29 to 42 with the NF-kappaB inhibitor
      pyrrolidine dithiocarbamate (PDTC) and/or from Days 1 to 21 with anti-IL-6
      antibody. Nuclear staining for NF-kappaB, an indicator of the activation of the
      classical NF-kappaB pathway, was detected in pulmonary arterial lesions of
      patients with iPAH and SuHx rats. NF-kappaB inhibition with PDTC prevented and
      reduced pulmonary arterial obliteration without reducing muscularization.
      However, the elevated lung levels of IL-6 were not reduced in PDTC-treated SuHx
      animals. PDTC treatment prevented or reduced apoptosis of pulmonary artery wall
      cells and pulmonary arterial obliteration. IL-6 inhibition had only a partial
      effect on apoptosis and obliteration. Pulmonary arterial media wall thickness was
      not affected by any of these treatments. Preventive and therapeutic PDTC
      treatment promoted immune regulation by increasing the number of perivascular
      CD4(+) T cells, in particular regulatory T cells (early treatment), and by
      reducing the number of perivascular CD8(+) T lymphocytes and CD45RA(+) B
      lymphocytes. Therapeutic PDTC treatment further preserved right ventricular
      function in SuHx animals. Inhibition of NF-kappaB may represent a therapeutic
      option for pulmonary arterial obliteration via reduced vessel wall cell apoptosis
      and improved regulation of the immune system. 

PMID- 24684444
TI  - Self-assembly of Co3V2O8 multilayered nanosheets: controllable synthesis,
      excellent Li-storage properties, and investigation of electrochemical mechanism.
AB  - Developing electrode materials with both high energy and power densities holds
      the key for satisfying the urgent demand of energy storage worldwide. Herein, we
      demonstrate the successful preparation of Co3V2O8 nanostructures that are
      constructed from self-assembly of ultrathin nanosheets via a simple hydrothermal
      method followed by annealing in air at 350  degrees C for 2 h. A "slipping
      exfoliating-self reassembly" model based on the time-dependent experiments was
      proposed to elucidate the formation of the hierarchical nanosheets. When tested
      as lithium ion anodes, the as-synthesized multilayered nanoarchitectures exhibit
      outstanding reversible capacity (1114 mA h g(-1) retained after 100 cycles) and
      excellent rate performance (361 mA h g(-1) at a high current density of 10 A g(
      1)) for lithium storage. Detailed investigations of the morphological and
      structural changes of Co3V2O8 upon cycling reveal an interesting kinetics toward
      lithium ion intercalations, where reversible conversion reactions between Co and
      CoO are found proceeding on the amorphous lithiated vanadium oxides matrixes. We
      believe that this observation is a valuable discovery for metal vandates-based
      lithium ion anodes. The superior electrochemical performances of the multilayered
      Co3V2O8 nanosheets can be attributed to the unique morphologies and particularly
      the surface-to-surface constructions that are generated during the lithium ion
      insertion processes. 

PMID- 24684443
TI  - Economic burden of back and neck pain: effect of a neuropathic component.
AB  - This was a retrospective database analysis (2001-2009) of employees' medical,
      prescription drug, and absence costs and days from sick leave, short- and long
      term disability, and workers' compensation. Employees with an ICD-9 diagnostic
      code for back or neck pain and an ICD-9 for a back- or neck-related neuropathic
      condition (eg, myelopathy, compression of the spinal cord, neuritis, radiculitis)
      or radiculopathy were considered to have nociceptive back or neck pain with a
      neuropathic component. Employees with an ICD-9 for back pain or neck pain and no
      ICD-9 for a back- or neck-related neuropathic condition or radiculopathy were
      defined to have nociceptive back or neck pain. Patients with nociceptive back or
      neck pain with a neuropathic component were classified as having or not having
      prior nociceptive pain. Annual costs (medical and prescription drug costs and
      absence costs) and days from sick leave, short- and long-term disability, and
      workers' compensation were evaluated. Mean annual total costs were highest
      ($8512) for nociceptive pain with a neuropathic component with prior nociceptive
      pain (n=9162 employees), $7126 for nociceptive pain with a neuropathic component
      with no prior nociceptive pain (n=5172), $5574 for nociceptive pain only
      (n=35,347), and $3017 for control employees with no back or neck pain diagnosis
      (n=226,683). Medical, short-term disability, and prescription drugs yielded the
      highest incremental costs compared to controls. Mean total absence days/year were
      8.26, 7.86, 5.70, and 3.44, respectively. The economic burden of back pain or
      neck pain is increased when associated with a neuropathic component.

PMID- 24684446
TI  - Short-term memory capacity in networks via the restricted isometry property.
AB  - Cortical networks are hypothesized to rely on transient network activity to
      support short-term memory (STM). In this letter, we study the capacity of
      randomly connected recurrent linear networks for performing STM when the input
      signals are approximately sparse in some basis. We leverage results from
      compressed sensing to provide rigorous nonasymptotic recovery guarantees,
      quantifying the impact of the input sparsity level, the input sparsity basis, and
      the network characteristics on the system capacity. Our analysis demonstrates
      that network memory capacities can scale superlinearly with the number of nodes
      and in some situations can achieve STM capacities that are much larger than the
      network size. We provide perfect recovery guarantees for finite sequences and
      recovery bounds for infinite sequences. The latter analysis predicts that network
      STM systems may have an optimal recovery length that balances errors due to
      omission and recall mistakes. Furthermore, we show that the conditions yielding
      optimal STM capacity can be embodied in several network topologies, including
      networks with sparse or dense connectivities. 

PMID- 24684447
TI  - Neural decoding with kernel-based metric learning.
AB  - In studies of the nervous system, the choice of metric for the neural responses
      is a pivotal assumption. For instance, a well-suited distance metric enables us
      to gauge the similarity of neural responses to various stimuli and assess the
      variability of responses to a repeated stimulus-exploratory steps in
      understanding how the stimuli are encoded neurally. Here we introduce an approach
      where the metric is tuned for a particular neural decoding task. Neural spike
      train metrics have been used to quantify the information content carried by the
      timing of action potentials. While a number of metrics for individual neurons
      exist, a method to optimally combine single-neuron metrics into multineuron, or
      population-based, metrics is lacking. We pose the problem of optimizing
      multineuron metrics and other metrics using centered alignment, a kernel-based
      dependence measure. The approach is demonstrated on invasively recorded neural
      data consisting of both spike trains and local field potentials. The experimental
      paradigm consists of decoding the location of tactile stimulation on the forepaws
      of anesthetized rats. We show that the optimized metrics highlight the
      distinguishing dimensions of the neural response, significantly increase the
      decoding accuracy, and improve nonlinear dimensionality reduction methods for
      exploratory neural analysis. 

PMID- 24684449
TI  - Direct learning of sparse changes in Markov networks by density ratio estimation.
AB  - We propose a new method for detecting changes in Markov network structure between
      two sets of samples. Instead of naively fitting two Markov network models
      separately to the two data sets and figuring out their difference, we directly
      learn the network structure change by estimating the ratio of Markov network
      models. This density-ratio formulation naturally allows us to introduce sparsity
      in the network structure change, which highly contributes to enhancing
      interpretability. Furthermore, computation of the normalization term, a critical
      bottleneck of the naive approach, can be remarkably mitigated. We also give the
      dual formulation of the optimization problem, which further reduces the
      computation cost for large-scale Markov networks. Through experiments, we
      demonstrate the usefulness of our method. 

PMID- 24684448
TI  - On nonnegative matrix factorization algorithms for signal-dependent noise with
      application to electromyography data.
AB  - Nonnegative matrix factorization (NMF) by the multiplicative updates algorithm is
      a powerful machine learning method for decomposing a high-dimensional nonnegative
      matrix V into two nonnegative matrices, W and H, where V ~ WH. It has been
      successfully applied in the analysis and interpretation of large-scale data
      arising in neuroscience, computational biology, and natural language processing,
      among other areas. A distinctive feature of NMF is its nonnegativity constraints
      that allow only additive linear combinations of the data, thus enabling it to
      learn parts that have distinct physical representations in reality. In this
      letter, we describe an information-theoretic approach to NMF for signal-dependent
      noise based on the generalized inverse gaussian model. Specifically, we propose
      three novel algorithms in this setting, each based on multiplicative updates, and
      prove monotonicity of updates using the EM algorithm. In addition, we develop
      algorithm-specific measures to evaluate their goodness of fit on data. Our
      methods are demonstrated using experimental data from electromyography studies,
      as well as simulated data in the extraction of muscle synergies, and compared
      with existing algorithms for signal-dependent noise.

PMID- 24684450
TI  - A causal perspective on the analysis of signal and noise correlations and their
      role in population coding.
AB  - The role of correlations between neuronal responses is crucial to understanding
      the neural code. A framework used to study this role comprises a breakdown of the
      mutual information between stimuli and responses into terms that aim to account
      for different coding modalities and the distinction between different notions of
      independence. Here we complete the list of types of independence and distinguish
      activity independence (related to total correlations), conditional independence
      (related to noise correlations), signal independence (related to signal
      correlations), coding independence (related to information transmission), and
      information independence (related to redundancy). For each type, we identify the
      probabilistic criterion that defines it, indicate the information-theoretic
      measure used as statistic to test for it, and provide a graphical criterion to
      recognize the causal configurations of stimuli and responses that lead to its
      existence. Using this causal analysis, we first provide sufficiency conditions
      relating these types. Second, we differentiate the use of the measures as
      statistics to test for the existence of independence from their use for
      quantification. We indicate that signal and noise correlation cannot be
      quantified separately. Third, we explicitly define alternative system
      configurations used to construct the measures, in which noise correlations or
      noise and signal correlations are eliminated. Accordingly, we examine which
      measures are meaningful only as a comparison across configurations and which ones
      provide a characterization of the actually observed responses without resorting
      to other configurations. Fourth, we compare the commonly used nonparametric
      approach to eliminate noise correlations with a functional (model-based)
      approach, showing that the former approach does not remove those effects of noise
      correlations captured by the tuning properties of the individual neurons, and
      implies nonlocal causal structure manipulations. These results improve the
      interpretation of the measures on the framework and help in understanding how to
      apply it to analyze the role of correlations. 

PMID- 24684451
TI  - Toward unified hybrid simulation techniques for spiking neural networks.
AB  - In the field of neural network simulation techniques, the common conception is
      that spiking neural network simulators can be divided in two categories: time
      step-based and event-driven methods. In this letter, we look at state-of-the art
      simulation techniques in both categories and show that a clear distinction
      between both methods is increasingly difficult to define. In an attempt to
      improve the weak points of each simulation method, ideas of the alternative
      method are, sometimes unknowingly, incorporated in the simulation engine. Clearly
      the ideal simulation method is a mix of both methods. We formulate the key
      properties of such an efficient and generally applicable hybrid approach. 

PMID- 24684452
TI  - Adaptive multiclass classification for brain computer interfaces.
AB  - We consider the problem of multiclass adaptive classification for brain-computer
      interfaces and propose the use of multiclass pooled mean linear discriminant
      analysis (MPMLDA), a multiclass generalization of the adaptation rule introduced
      by Vidaurre, Kawanabe, von Bunau, Blankertz, and Muller (2010) for the binary
      class setting. Using publicly available EEG data sets and tangent space mapping
      (Barachant, Bonnet, Congedo, & Jutten, 2012) as a feature extractor, we
      demonstrate that MPMLDA can significantly outperform state-of-the-art multiclass
      static and adaptive methods. Furthermore, efficient learning rates can be
      achieved using data from different subjects.

PMID- 24684453
TI  - Dhilirolides E-N, meroterpenoids produced in culture by the fungus Penicillium
      purpurogenum collected in Sri Lanka: structure elucidation, stable isotope
      feeding studies, and insecticidal activity.
AB  - Extracts of laboratory cultures of the fungus Penicilium purpurogenum obtained
      from rotting fruit of the tree Averrhoa bilimbi growing in Sri Lanka have yielded
      10 new meroterpenoids, dhilirolides E-N (5-14). The structures of the new
      dhilirolides have been elucidated by analysis of spectroscopic data and a single
      crystal X-ray diffraction analysis of dhilirolide L (12). Dhilirolides A-N (1-14)
      represent the four unprecedented and rearranged dhilirane, isodhilirane, 14,15
      dinordhilirane, and 23,24-dinorisodhilirane meroterpenoid carbon skeletons.
      Stable isotope feeding studies have confirmed the meroterpenoid biogenetic origin
      of the dhilirolides and provided support for a proposed genesis of the new carbon
      skeletons. Dhilirolide L (12) showed significant feeding inhibition and sublethal
      developmental disruption in the cabbage looper Trichoplusia ni, an important
      agricultural pest, at low concentrations. 

PMID- 24684454
TI  - Pd(II)-catalyzed intermolecular arylation of unactivated C(sp3)-H bonds with aryl
      bromides enabled by 8-aminoquinoline auxiliary.
AB  - An example of using readily available, less reactive aryl bromides as arylating
      reagents in the Pd(II)-catalyzed intermolecular arylation of unactivated C(sp(3))
      H bonds is described. This reaction was promoted by a crucial 8-aminoquinolinyl
      directing group and a K2CO3 base, enabling regiospecific installation of an aryl
      scaffold at the beta-position of carboxamides. A mechanistic study by DFT
      calculations reveals a C(sp(3))-H activation-led pathway featuring the oxidative
      addition as the highest energy transition state. 

PMID- 24684455
TI  - Laser ablation and 131-iodine: a 24-month pilot study of combined treatment for
      large toxic nodular goiter.
AB  - CONTEXT: It is normally recognized that the preferred treatment in large toxic
      thyroid nodules should be thyroidectomy. OBJECTIVE: The aim of the study was to
      assess the efficacy of combined laser ablation treatment (LAT) and radioiodine
      131 (131I) treatment of large thyroid toxic nodules with respect to rapidity of
      control of local symptoms, of hyperthyroidism, and of reduction of administered
      131I activity in patients at refusal or with contraindications to surgery. DESIGN
      AND SETTING: We conducted a pilot study at a single center specializing in
      thyroid care. PATIENTS: Fifteen patients were treated with LAT, followed by 131I
      (group A), and a series of matched consecutive patients were treated by 131I only
      (group B). INTERVENTION(S): Laser energy was delivered with an output power of 3
      W (1800 J per fiber per treatment) through two 75-mm, 21-gauge spinal needles.
      Radioiodine activity was calculated to deliver 200 Gy to the hyperfunctioning
      nodule. MAIN OUTCOME MEASURE(S): Thyroid function, thyroid peroxidase antibody,
      thyroglobulin antibody, ultrasound, and local symptoms were measured at baseline
      and up to 24 months. RESULTS: Nodule volume reduction at 24 months was: 71.3 +/-
      13.4 vs 47.4 +/- 5.5%, group A (LAT+131I) vs group B (131I), respectively; P <
      .001). In group A (LAT+131I), a reduction in radioiodine-administered activity
      was obtained (-21.1 +/- 8.1%). Local symptom score demonstrated a more rapid
      reduction in group A (LAT+131I). In three cases, no 131I treatment was needed
      after LAT. CONCLUSIONS: In this pilot study, combined LAT/131I treatment induced
      faster and greater improvement of local and systemic symptoms compared to 131I
      only. This approach seems a possible alternative to thyroidectomy in patients at
      refusal of surgery.

PMID- 24684456
TI  - Impact of vitamin D3 dietary supplement matrix on clinical response.
AB  - CONTEXT: As a result of research suggesting increased health risk with low serum
      25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it
      frequently. Providers and patients are faced with treatment choices when low
      status is identified. OBJECTIVE: To compare the safety and efficacy of three
      vitamin D3 dietary supplements with different delivery matrices. SETTING AND
      DESIGN: A 12-week, parallel group, single-masked, clinical trial was conducted in
      Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with
      (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements,
      ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated
      powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was
      assessed by a third party and the results adjusted based on the actual D3 content
      administered. Mean change in 25(OH)D/mcg D3 administered; difference in the
      proportion of D3 insufficient participants (ie, 25(OH)D <=30 ng/mL) reaching
      sufficiency (ie, 25(OH)D >=30 ng/mL); and mean change in serum 1, 25
      dihydroxycholecalciferol were measured. RESULTS: In two of the three products
      tested, the measured vitamin D3 content varied considerably from the label
      claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly
      different between groups (P = .04; n = 55). Pairwise comparisons demonstrated
      DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was
      not different from CAP. The proportions reaching sufficiency were: 100% (TAB and
      CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25
      Dihydroxycholecalciferol did not change significantly in any group. CONCLUSIONS:
      Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum
      25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than
      chewable or encapsulated supplements.

PMID- 24684457
TI  - ZIC1 is a putative tumor suppressor in thyroid cancer by modulating major
      signaling pathways and transcription factor FOXO3a.
AB  - CONTEXT: ZIC1 has been reported to be overexpressed and plays an oncogenic role
      in some brain tumors, whereas it is inactivated by promoter hypermethylation and
      acts as a tumor suppressor in gastric and colorectal cancers. However, until now,
      its biological role in thyroid cancer remains totally unknown. OBJECTIVES: The
      aim of this study is to explore the biological functions and related molecular
      mechanism of ZIC1 in thyroid carcinogenesis. SETTING AND DESIGN: Quantitative RT
      PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes.
      Methylation-specific PCR was used to analyze promoter methylation of the ZIC1
      gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were
      determined by cell proliferation and colony formation, cell cycle and apoptosis,
      as well as cell migration and invasion assays. RESULTS: ZIC1 was frequently down
      regulated by promoter hypermethylation in both primary thyroid cancer tissues and
      thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation
      was significantly associated with lymph node metastasis in patients with
      papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid
      cancer cells dramatically inhibited cell proliferation, colony formation,
      migration and invasion, and induced cell cycle arrest and apoptosis by blocking
      the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and
      RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity.
      CONCLUSIONS: Our data demonstrate that ZIC1 is frequently inactivated by promoter
      hypermethyaltion and functions as a tumor suppressor in thyroid cancer through
      modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

PMID- 24684458
TI  - H-RAS mutations are restricted to sporadic pheochromocytomas lacking specific
      clinical or pathological features: data from a multi-institutional series.
AB  - CONTEXT: Somatic or germline mutations in up to 15 disease-causative genes are
      detectable in up to 50% of patients with pheochromocytoma (PCC) and paraganglioma
      (PGL). Very recently, somatic H-RAS mutations were identified by exome sequencing
      in approximately 7% in sporadic PCCs and PGLs, in association with male sex and
      benign behavior. OBJECTIVE: To explore the prevalence of RAS mutations in a
      cohort of 271 PCC and PGL from a European registry and to compare the genotype
      with clinical and pathological characteristics of potential clinical interest.
      SETTING AND DESIGN: Genetic screening for hotspot mutations in H-, N-, and K-RAS
      genes was performed by means of Sanger sequencing or pyrosequencing methods on
      tumor DNA in a series of patients with (n = 107) or without (n = 164) germline or
      somatic PCC/PGL-related gene mutations. RESULTS: Overall, H-RAS mutations were
      detected in 5.2% of cases (14/271), which were confined to sporadic PCCs
      resulting in a prevalence of 10% (14/140) in this cohort. In contrast, no
      mutations were found in PCC with PCC/PGL-related gene mutations (0/76) or in PGL
      (0/55) harboring or not mutations in PCC/PGL susceptibility genes. In this large
      series, H-RAS mutations in PCCs lacked any significant correlation with
      pathological or basic clinical endpoints. CONCLUSIONS: Somatic H-RAS mutations
      are restricted to a relevant proportion of sporadic PCC. These findings provide
      the basis to study potential H-RAS-dependent correlations with long-term outcome
      data.

PMID- 24684459
TI  - The impact of obesity on the presentation of primary hyperparathyroidism.
AB  - CONTEXT: Obesity has been associated with elevated serum PTH (sPTH) in the
      general population. Obesity may also alter the clinical presentation in patients
      with primary hyperparathyroidism (PHPT). OBJECTIVES: The objectives of the study
      were to compare the clinical presentation of obese (OB) vs nonobese (NO) PHPT
      patients and to assess the impact of obesity on the presentation of PHPT
      independent of serum calcium and PTH. PATIENTS: Consecutive PHPT patients who
      underwent parathyroidectomy between 2003 and 2012 by a single surgical group
      participated in the study. SETTING: The study was conducted at an academic
      medical center. DESIGN: Cross-sectional review of records of preoperative
      demographic, historical, laboratory, and densitometry findings and intraoperative
      pathological findings were compared in OB vs NO patients. MAIN OUTCOME MEASURES:
      The prevalence of nephrolithiasis and osteoporosis was measured. RESULTS: Two
      hundred forty-seven PHPT patients were included in this analysis. Fifty percent
      were OB and 79% were women. Mean body mass index was 25.3 +/- 3.3 and 36.0 +/-
      5.2 kg/m(2) in the NO and OB groups, respectively. Age, gender, and race
      distribution was similar between the two groups. Serum calcium was similar
      between the groups (11.0 +/- 0.7 mg/dL in NO vs 11.1 +/- 0.9 mg/dL in OB, P =
      .13), whereas sPTH was higher in OB (151 +/- 70 vs 136 +/- 69 pg/mL, P = .03).
      The OB group exhibited higher prevalence of hypercalciuria (urine calcium > 400
      mg per 24 h) (41% vs 23% in NO, P = .01) and nephrolithiasis (36% vs 21% in NO, P
      = .03). Despite higher sPTH, OB patients showed higher bone mineral density and a
      lower rate of osteoporosis (21% vs 35%, P = .05). Differences in the prevalence
      of hypercalciuria and osteoporosis between the groups persisted after adjustment
      for age, race, estimated glomerular filtration rate, gender, sPTH, and calcium.
      CONCLUSIONS: In PHPT patients, obesity is a risk factor for hypercalciuria and
      nephrolithiasis and is protective against osteoporosis. The impact of
      parathyroidectomy on the clinical features of obese PHPT patients merits further
      evaluation.

PMID- 24684460
TI  - Higher estrogen levels during pregnancy in Andean than European residents of high
      altitude suggest differences in aromatase activity.
AB  - CONTEXT: Uteroplacental hypoxia has been reported to lower estrogen levels in
      preeclampsia as the result of reduced aromatase activity. OBJECTIVE: We asked
      whether the chronic hypoxia of residence at high altitude in the absence of
      preeclampsia lowered estrogen, whether such effects differed in Andean vs
      European high-altitude residents, and whether such effects were related to
      uterine artery diameter or blood flow. DESIGN, SETTING, AND PARTICIPANTS: Studies
      at weeks 20 and 36 of pregnancy were conducted in 108 healthy Bolivian low- (400
      m, n = 53) or high-altitude (3600 m, n = 55) residents of European (n = 28 low
      and 26 high altitude) or Andean (n = 25 low and 29 high altitude) ancestry. All
      groups were similar in age, nonpregnant body mass index, and pregnancy weight
      gain. RESULTS: High-altitude residence increased circulating progesterone,
      cortisol, estrone, 17beta-estradiol, and estriol levels (all P < .01). High
      altitude Andeans vs Europeans at week 36 had higher progesterone, estrone, 17beta
      estradiol, and estriol levels as well as product to substrate ratios for the
      reactions catalyzed by aromatase, whereas week 36 cortisol levels were greater in
      the European than Andean women (all P < .05). Lower cortisol, higher estriol
      (both P < .01), and trends for higher progesterone and 17beta-estradiol levels
      were associated with greater uterine artery diameters and blood flow at high
      altitude. CONCLUSIONS: Chronic hypoxia does not lower but rather raises estrogen
      levels in multigenerational Andeans vs shorter-term Europeans, possibly as the
      result of greater aromatase activity. Because hypoxia alone does not lower
      estrogen, other attributes of the disease may be responsible for the lower
      estrogen levels seen previously in preeclamptic women.

PMID- 24684461
TI  - Human testicular peritubular cells host putative stem Leydig cells with
      steroidogenic capacity.
AB  - AIM: We aim to examine the steroidogenic phenotype and the differentiation
      potential of human testicular peritubular cells (HTPCs) and to explore their
      possible relationship to the adult Leydig cell lineage. BACKGROUND: The cells of
      the adult Leydig cell lineage may reside in the peritubular compartment of the
      testis. This suggestion is supported by the facts that the rodent peritubular
      cells can be differentiated toward this lineage and that cAMP enhances their
      steroidogenic potential. METHODS: Human testicular biopsies, and derived HTPCs,
      were analyzed by immunohistochemistry, RT-PCR, and Western blotting. After
      stimulation by forskolin or platelet-derived growth factor-BB, quantitative RT
      PCR was used to compare the levels of mRNAs encoding proteins involved in
      steroidogenesis and steroid production was analyzed by liquid chromatography and
      tandem mass spectrometry. RESULTS: Immunohistochemical analysis revealed that the
      peritubular cells that form the outer part of the tubular wall express platelet
      derived growth factor receptor-alpha. Furthermore, the pluripotency markers (POU
      domain class 5 transcription factor 1, GATA-binding protein 4), stem Leydig cell
      markers (platelet derived growth factor receptor-A, leukemia inhibitory factor
      receptor), and mRNAs encoding proteins involved in steroidogenesis (nuclear
      receptor subfamily 5, group A, member 1; steroidogenic acute regulatory protein;
      CYP11A1; CYP17A1; 3beta-hydroxysteroid dehydrogenase) were expressed by the
      HTPCs. Stimulation with forskolin increased the expression of the steroidogenic
      markers, which was accompanied by the production of pregnenolone and progesterone
      by HTPCs in vitro. Treatment with platelet-derived growth factor-BB induced
      expression of steroidogenic acute regulatory protein. CONCLUSIONS: Our results
      indicate that the tubular wall of the human testis is a reservoir for cells of
      the adult Leydig cell lineage and that the steroidogenic potential of these cells
      can be activated in culture.

PMID- 24684462
TI  - Downstream effects of maternal hypothyroxinemia in early pregnancy: nonverbal IQ
      and brain morphology in school-age children.
AB  - CONTEXT: Although maternal hypothyroxinemia is suggested to be related to various
      adverse consequences in a child's neurodevelopment, the underlying neurobiology
      is largely unknown. OBJECTIVE: The objective of the study was to examine the
      relationship between maternal hypothyroxinemia in early pregnancy and children's
      nonverbal intelligence quotient (IQ). Furthermore, we explored whether global
      brain volumes, cortical thickness, and brain surface area differed between
      children exposed prenatally to hypothyroxinemia and healthy controls. DESIGN AND
      SETTING: The study included a large population-based prospective birth cohort in
      The Netherlands. PARTICIPANTS: A total of 3727 mother-child pairs with data on
      prenatal thyroid function at less than 18 weeks of gestation and nonverbal IQ at
      6 years participated in the study. In 652 children, brain imaging was performed
      at 8 years of age. MAIN MEASURES: Maternal hypothyroxinemia was defined as free
      T4 in the lowest 5% of the sample, whereas TSH was in the normal range. At 6
      years, children's IQ was assessed using a Dutch test battery. Global brain
      volumetric measures, cortical thickness, and surface area were assessed using
      high-resolution structural magnetic resonance imaging. RESULTS: The children of
      mothers with hypothyroxinemia in early pregnancy scored 4.3 points IQ lower than
      the children of mothers with normal thyroid status (95% confidence interval 
      6.68, -1.81; P = .001). After adjustment for multiple testing, we did not find
      any differences in brain volumetric measures, cortical thickness, and surface
      area between children exposed prenatally to hypothyroxinemia and controls.
      CONCLUSIONS: Our findings confirm a large adverse effect of maternal
      hypothyroxinemia on children's nonverbal IQ at school age. However, we found no
      evidence that maternal hypothyroxinemia is associated with differences in brain
      morphology in school-age children.

PMID- 24684463
TI  - Genetic analysis in young-age-of-onset Graves' disease reveals new susceptibility
      loci.
AB  - CONTEXT: Genetic and environmental factors play an essential role in the
      pathogenesis of Graves' Disease (GD). Children with GD have less exposure time to
      environmental factors and therefore are believed to harbor stronger genetic
      susceptibility than adults. OBJECTIVE: The aim of the study was to identify
      susceptibility loci that predispose to GD in patients with young-age-of-onset
      (YAO) GD. SETTING AND DESIGN: One hundred six patients with YAO GD (onset <30 y)
      and 855 healthy subjects were studied. Cases and controls were genotyped using
      the Illumina Infinium Immunochip, designed to genotype 196,524 polymorphisms.
      Case control association analyses were performed using the PLINK computer
      package. Ingenuity Pathway Analysis program (QIAGEN) was used to carry out
      pathway analyses. RESULTS: Immunochip genetic association analysis identified 30
      single-nucleotide polymorphisms in several genes that were significantly
      associated with YAO GD, including major histocompatibility complex class I and
      class II genes, BTNL2, NOTCH4, TNFAIP3, and CXCR4. Candidate gene analysis
      revealed that most of the genes previously shown to be associated with adult
      onset GD were also associated with YAO GD. Pathway analysis demonstrated that
      antigen presentation, T-helper cell differentiation, and B cell development were
      the major pathways contributing to the pathogenesis of YAO GD. CONCLUSIONS:
      Genetic analysis identified novel susceptibility loci in YAO GD adding a new
      dimension to the understanding of GD etiology.

PMID- 24684464
TI  - Regulation of energy metabolism and mitochondrial function in skeletal muscle
      during lipid overfeeding in healthy men.
AB  - CONTEXT/OBJECTIVE: The aim of this study was to evaluate the regulation of the
      fuel partitioning and energy metabolism in skeletal muscle during lipid
      overfeeding in healthy men. Design/Participants/Intervention: Thirty-nine healthy
      volunteers were overfed for 56 days with a high-fat diet (3180 kJ/d). Energy
      metabolism (indirect calorimetry) was characterized in the fasting state and
      during a test meal before and at the end of the diet. Skeletal muscle biopsies
      were taken at day 0 and day 56. MAIN OUTCOME MEASURES: Change in gene expression,
      mitochondrial respiration, nicotinamide adenine dinucleotide (NAD(+)) content,
      and acetylation of peroxisome proliferator-activated receptor-gamma coactivator
      1alpha (PGC-1alpha) in skeletal muscle was measured. RESULTS: Overfeeding
      increased body weight (+2.6 kg) and fat mass concomitantly with a shift in the
      use of substrates as energy fuel toward preferential oxidation of carbohydrates
      instead of lipids. Changes in lipid metabolic gene expression supported this
      observation, with a reduction in pyruvate dehydrogenase kinase 4 expression that
      could be the consequences of decreased NAD(+) concentration and reduced
      deacetylase activity of the sirtuins, as supported by hyperacetylation of PGC
      1alpha after overfeeding. Interestingly, this reduction of the sirtuin PGC-1alpha
      pathway was associated with increased mitochondrial gene expression and higher
      respiration rate under these conditions. CONCLUSION: Adaptation to lipid
      overfeeding and regulation of fuel partitioning in human muscle appear to rely on
      a dissociation between the regulatory functions of the sirtuin-PGC-1alpha pathway
      on fatty acid oxidation and on mitochondrial regulation. This may facilitate
      lipid storage during a period of positive energy balance while maintaining
      mitochondrial functions and oxidative capacities.

PMID- 24684465
TI  - Interactions between dietary calcium intake and bone mineral density or bone
      geometry in a low calcium intake population (KNHANES IV 2008-2010).
AB  - CONTEXT: Little is known about the interactions between dietary calcium intake
      and bone strength parameters in populations or areas with low calcium intake.
      OBJECTIVE: The objective of the study was to investigate the relationship between
      dietary calcium intake and bone mineral density (BMD) or bone geometry in an
      Asian population with low calcium intake. DESIGN AND SETTING: This was a cross
      sectional study of data from the Korea National Health and Nutrition Examination
      Survey, 2008-2010. PARTICIPANTS: A total of 3448 men and 3812 women older than 50
      years were stratified by daily dietary calcium intake: less than 400 mg/d, 400
      799 mg/d, 800-1199 mg/d, and 1200 mg/d or greater. MAIN OUTCOME MEASURES: BMD was
      measured by dual-energy X-ray absorptiometry and the geometric index was
      calculated. RESULTS: Mean daily calcium intake was 470 mg/d in this population.
      BMD in the lumbar spine (both sexes) and femoral neck (women) was significantly
      lower only when calcium intake was less than 400 mg/d. In men, femoral neck and
      total hip BMD was positively related to calcium intake up to 1200 mg/d. Calcium
      intake less than 400 mg/d was negatively related to femoral cortical thickness
      and buckling ratio. These interactions disappeared when the 25-hydroxyvitamin D
      level was 30 ng/mL or greater in men and 20 ng/mL or greater in women.
      CONCLUSIONS: Low calcium intake was significantly related with low BMD and
      increased risk of osteoporosis. However, the association between calcium and BMD
      was not consistently linear, and a sufficient vitamin D level appears to
      compensate for the negative influences of low calcium intake on bone.

PMID- 24684467
TI  - Cost-effectiveness of molecular testing for thyroid nodules with atypia of
      undetermined significance cytology.
AB  - CONTEXT: Novel molecular diagnostics, such as the gene expression classifier
      (GEC) and gene mutation panel (GMP) testing, may improve the management for
      thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost
      effectiveness of an approach combining both tests in different practice settings
      in North America is unknown. OBJECTIVE: The aim of the study was to determine the
      cost-effectiveness of two diagnostic molecular tests, singly or in combination,
      for AUS thyroid nodules. DESIGN AND SETTING: We constructed a microsimulation
      model to investigate cost-effectiveness from US (Medicare) and Canadian
      healthcare system perspectives. PATIENTS: Low-risk patients with AUS thyroid
      nodules were simulated. INTERVENTIONS: We examined five management strategies: 1)
      routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP +
      selective GEC; and 5) standard management. MAIN OUTCOME MEASURES: Lifetime costs
      and quality-adjusted life-years were measured. RESULTS: From the US perspective,
      the routine GEC + selective GMP strategy was the dominant strategy. From the
      Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030
      per quality-adjusted life-year gained over standard management, and was dominant
      over the other strategies. Sensitivity analyses reported that the decisions from
      both perspectives were sensitive to variations in the probability of malignancy
      in the nodule and the costs of the GEC and GMP. The probability of cost
      effectiveness for routine GEC + selective GMP was low. CONCLUSIONS: In the US
      setting, the most cost-effective strategy was routine GEC + selective GMP. In the
      Canadian setting, standard management was most likely to be cost effective. The
      cost of these molecular diagnostics will need to be reduced to increase their
      cost-effectiveness for practice settings outside the United States.

PMID- 24684466
TI  - Teriparatide increases strength of the peripheral skeleton in premenopausal women
      with idiopathic osteoporosis: a pilot HR-pQCT study.
AB  - CONTEXT: In premenopausal women with idiopathic osteoporosis (IOP), treatment
      with teriparatide leads to substantial improvement in bone density and quality at
      central skeletal sites. The effects of teriparatide may differ on cortical and
      trabecular bone and also at the central and the peripheral skeleton. OBJECTIVE:
      The objective of the study was to determine whether teriparatide was associated
      with improvements in compartmental volumetric bone mineral density (BMD), bone
      microarchitecture, and estimated bone strength of the distal radius and tibia as
      assessed by high-resolution peripheral quantitative computed tomography. DESIGN,
      SETTING, AND PARTICIPANTS: Premenopausal women (n = 20, age 41 +/- 5 y) with IOP
      (low trauma fractures and/or Z-scores <= -2.0) were scanned with high-resolution
      peripheral quantitative computed tomography at baseline and after 18 months of
      teriparatide treatment. Cortical and trabecular volumetric BMD and
      microarchitecture were measured by both standard and advanced techniques,
      including individual trabecula segmentation, and bone strength was estimated by
      finite element analysis. MAIN OUTCOME MEASURES: The total volumetric BMD and
      homogeneous bone stiffness were measured. RESULTS: Trabecular volumetric BMD
      increased significantly by 2.6% (1.8, 6.2) [median (interquartile range)] at the
      radius and 2.5% (1.1, 3.6) at the tibia. In addition, trabecular plate bone
      volume fraction increased by 9.1% (2.1, 17.1) at the radius and 7.6% (1.0, 9.7)
      at the tibia. Cortical thickness and volumetric density did not change; however,
      cortical porosity increased at the radius but not at the tibia. Despite these
      changes, whole-bone stiffness and failure load estimated by finite element
      analysis increased at both the radius and tibia. CONCLUSIONS: In premenopausal
      women with IOP, 18 months of teriparatide was associated with increases in
      trabecular volumetric BMD, improved trabecular microarchitecture, and estimated
      bone strength at both the radius and tibia.

PMID- 24684469
TI  - Gradual development of brachydactyly in pseudohypoparathyroidism.

PMID- 24684468
TI  - Pharmacokinetic-pharmacodynamic study of subcutaneous injection of depot
      nandrolone decanoate using dried blood spots sampling coupled with ultrapressure
      liquid chromatography tandem mass spectrometry assays.
AB  - CONTEXT: Testosterone (T) and nandrolone (N) esters require deep im injections by
      medical personnel but these often deposit injectate into sc fat so that more
      convenient sc self-administration may be feasible. OBJECTIVE: To investigate the
      feasibility and pharmacology of sc injection of N decanoate in healthy men using
      dried blood spot (DBS) for frequent blood sampling without clinic visits. SETTING
      AND DESIGN: Healthy male volunteers received 100 mg N decanoate by a single sc
      injection. Finger-prick capillary blood was spotted onto filter paper before
      injection daily at home for 21 d and stored at room temperature. Venous whole
      blood was also spotted onto filter paper before and weekly for 3 wk after
      injection. DBS were extracted for assay of N and T by liquid chromatography
      tandem mass spectrometry in a single batch with serum concentrations estimated
      with adjustment for capillary blood sample volume and hematocrit to define peak
      (N) or nadir (T) time and concentration from individual daily measurements.
      RESULTS: Daily serum N peaked 2.50 +/- 0.25 (SEM) ng/mL at a median (range) of 6
      (4-13) days causing a reduction in serum T from 3.50 +/- 0.57 ng/mL at baseline
      to a nadir of 0.38 +/- 0.13 (SEM) ng/mL (89 +/- 3% suppression) at a median
      (range) of 8 (5-16) days. Simultaneously sampled capillary, venous whole blood,
      and serum gave almost identical results for serum T and N. Finger-pricks and sc
      injections were well tolerated. CONCLUSIONS: This study demonstrates that A) DBS
      sampling with liquid chromatography mass spectrometry steroid analysis achieves
      frequent time sampling in the community without requiring clinic visits,
      venesection, or frozen serum storage, and B) androgen esters in an oil vehicle
      can be delivered effectively by sc injection, thus avoiding the need for
      medically supervised deep-im injections.

PMID- 24684470
TI  - Electronic spectroscopy of 1-(phenylethynyl)naphthalene.
AB  - Recently 1-(phenylethynyl)naphthalene (1-PEN) was suggested to be the primary
      dimerization product of phenylpropargyl radicals and therefore an important
      polycyclic hydrocarbon in combustion processes. Here we describe a spectroscopic
      investigation of a genuine 1-PEN sample by several complementary techniques,
      infrared spectroscopy, multiphoton ionization (MPI), and threshold photoelectron
      spectroscopy. The infrared spectrum recorded in a gas cell confirms that 1-PEN is
      indeed the previously observed dimerization product of phenylpropargyl. The
      origin of the transition into the electronically excited S1 state lies at 30823
      cm(-1), as found by MPI. Considerable vibrational activity is observed, and a
      number of low-wavenumber bands are assigned to a progression in the torsional
      motion. Values of 6 cm(-1) (S0) and 17 cm(-1) (S1) were derived for the
      fundamental of the torsion. In the investigated energy range the excited state
      lifetimes are in the nanosecond range. Spectra of the 1-PEN/Ar cluster exhibit a
      red shift of the electronic origin of 22 cm(-1), in good agreement with other
      aromatic molecules. A threshold photoelectron spectrum recorded using synchrotron
      radiation yields an ionization energy of 7.58 eV for 1-PEN. An excited electronic
      state of the cation is found at 7.76 eV, and dissociative photoionization does
      not set in below 15 eV. 

PMID- 24684471
TI  - Epidermal coumaroyl anthocyanins protect sweet basil against excess light stress:
      multiple consequences of light attenuation.
AB  - The putative photoprotective role of foliar anthocyanins continues to attract
      heated debate. Strikingly different experimental set-ups coupled with a poor
      knowledge of anthocyanin identity have likely contributed to such disparate
      opinions. Here, the photosynthetic responses to 30 or 100% solar irradiance were
      compared in two cultivars of basil, the green-leafed Tigullio (TG) and the purple
      leafed Red Rubin (RR). Coumaroyl anthocyanins in RR leaf epidermis significantly
      mitigated the effects of high light stress. In full sunlight, RR leaves displayed
      several shade-plant traits; they transferred less energy than did TG to
      photosystem II (PSII), and non-photochemical quenching was lower. The higher
      xanthophyll cycle activity in TG was insufficient to prevent inactivation of PSII
      in full sunlight. However, TG was the more efficient in the shade; RR was far
      less able to accommodate a large change in irradiance. Investment of carbon to
      phenylpropanoid biosynthesis was more in RR than in TG in the shade, and was
      either greatly enhanced in TG or varied little in RR because of high sunlight.
      The metabolic cost of photoprotection was lower whereas light-induced increase in
      biomass production was higher in RR than in TG, thus making purple basil the more
      light tolerant. Purple basil appears indeed to display the conservative resource
      use strategy usually observed in highly stress tolerant species. We conclude that
      the presence of epidermal coumaroyl anthocyanins confers protective benefits
      under high light, but it is associated with a reduced plasticity to accommodate
      changing light fluxes as compared with green leaves. 

PMID- 24684472
TI  - Idiopathic 'Half and half' nails.

PMID- 24684473
TI  - Olfaction evaluation and correlation with brain atrophy in Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome (BBS) is a well-recognized ciliopathy characterized by
      cardinal features namely: early onset retinitis pigmentosa, polydactyly, obesity,
      hypogonadism, renal and cognitive impairment. Recently, disorders of olfaction
      (anosmia, hyposmia) have been also described in BBS patients. Moreover,
      morphological brain anomalies have been reported and prompt for further
      investigations to determine whether they are primary or secondary to peripheral
      organ involvement (i.e. visual or olfactory neuronal tissue). The objective of
      this article is to evaluate olfactory disorders in BBS patients and to
      investigate putative correlation with morphological cerebral anomalies. To this
      end, 20 BBS patients were recruited and evaluated for olfaction using the
      University of Pennsylvania Smell Identification Test (UPSIT). All of them
      underwent a structural magnetic resonance imaging (MRI) scan. We first
      investigated brain morphological differences between BBS subjects and 14 healthy
      volunteers. Then, we showed objective olfaction disorders in BBS patients and
      highlight correlation between gray matter volume reduction and olfaction
      dysfunction in several brain areas. 

PMID- 24684475
TI  - Titratable acidity: a Pitts concept revisited.
AB  - Titratable Acidity (TA) in urine can be measured directly or calculated from
      actual and reference pH, by using the pKa2 6,8 for phosphate. In urine, H2PO4(-)
      represents the excretion of filtered H2PO4(-), filtrated HPO4(2-) being
      completely reabsorbed by the proximal tubule (the Van Slyke approach). Since
      excretion of H2PO4(-) frequently exceeds its glomerular filtration, this approach
      is considered inadequate by Pitts. He claimed that it is the tubular H(+)
      secretion which converts filtered HPO4(2-) to H2PO4(-), thereafter excreted in
      urine. This is only true under conditions of inorganic acid or neutral phosphate
      loading, when the maximum tubular phosphate reabsorption (TmPi) is overcharged.
      In controls, H2PO4(-) excretion is lower than its glomerular filtration, provided
      that acid-base status is normal and tubular phosphate reabsorption is below the
      TmPi. The TmPi is lower than its glomerular filtration, provided that acid-base
      status is normal and tubular phosphate reabsorption is below the TmPi. When the
      TmPi is exceeded, a portion of HPO4(2-) escapes proximal reabsorption, reaching
      the distal tubule where its absorption is precluded, while tubular H(+) secretion
      converts HPO4(2-) to H2PO4(-). In man and dog, the attainment of TmPi is
      evidenced by a FE% of 20%, and only beyond this limit H2PO4(-) excretion exceeds
      glomerular filtration. When FE% is lower than 20%, H2PO4(-) filtration exceeds
      excretion, HPO4(2-) being completely reabsorbed at the proximal tubule by NaPi-2a
      and 2c cotransporters. While Van Slyke's approach is always valid, Pitts'
      approach is only valid under loading conditions, when the two processes of H2PO4(
      ) excretion overlap each other. NH (+4) increases inversely to TA excretion in
      conditions of acidosis and tP restriction, but is independent of TA in Pi-replete
      dogs, independently of acidosis.

PMID- 24684474
TI  - Indirect estimation of age-related reference limits of thyroid parameters: a
      cross-sectional study of outpatients' results.
AB  - OBJECTIVES: Defining adequate reference limits (RLs) for thyroid hormones is an
      important task for support monitoring and the treatment of subclinical thyroid
      disease. We determined whether there are age-related RLs for thyroid parameters
      in male and female outpatients free of overt thyroid disease. DESIGN: We analyzed
      22,860 results (11,440 male and 11,420 female outpatients above the age of 18)
      for thyrotropin (TSH), free thyroxine (fT4) and total triiodothyronine (T3) that
      were stored in our laboratory information system between 2008 and 2011. We
      calculated the 2.5th and 97.5th centiles for the analyzed thyroid parameters.
      RESULTS: Our results indicate higher TSH levels with ageing, with a significant
      difference (p < 0.05) between the 97.5th centiles for males and females older
      than 70 (5.07 mIU/L and 4.10 mIU/L), but also a significant difference between
      male and female fT4 from 31 to 40 and from 41 to 50 years old (18.4 vs 14.9
      pmol/L and 19.0 vs 15.9 pmol/L, p < 0.05), respectively. Overall indirect
      estimates of the 97.5th centiles for TSH for males and females were not
      significantly different and were below the generally recommended upper limit
      (4.01 mIU/L and 4.20 mIU/L, respectively). In addition, we found no statistically
      significant change in mean T3 values in the analyzed population. CONCLUSIONS:
      This cross-sectional study indicates change in TSH and fT4 levels with ageing and
      gender-related upper limits. This suggests that by using indirect estimation a
      laboratory could provide clinicians with more accurate gender- and age-specific
      RLs for thyroid parameters.

PMID- 24684476
TI  - Novel intestinal-targeted Ca-alginate-based carrier for pH-responsive protection
      and release of lactic acid bacteria.
AB  - A novel intestinal-targeted carrier for pH-responsive protection of lactic acid
      bacteria in stomach and rapid release of lactic acid bacteria in small intestine
      is successfully developed. The proposed carrier is composed of a Ca
      alginate/protamine (CAP) composite shell and a Lactobacillus-casei-encapsulated
      Ca-alginate (CA) core. The carriers are prepared simply by a coextrusion
      minifluidic and subsequent adsorption method. The CAP composite shell offers not
      only improved protection for Lactobacillus casei to guarantee the endurance and
      survival in the stomach but also satisfactory intestinal-targeted characteristics
      to guarantee the rapid release of Lactobacillus casei in the small intestine. In
      the stomach, where there is an acidic environment, the diffusion channels
      delineated by the CA networks in the CAP composite shell of the carriers are
      choked with protamine molecules; as a result, it is hard for the gastric acid to
      diffuse across the CAP composite shell and thus the encapsulated Lactobacillus
      casei inside carriers can be efficiently protected. However, when they come to
      the small intestine, where there is a neutral environment, the carriers dissolve
      rapidly because of the cooperation between protamine and trypsin; consequently,
      the encapsulated Lactobacillus casei can be quickly released. The proposed CAP
      composite carrier provides a novel mode for developing efficient protection
      systems, responsive controlled-release systems, and intestinal-targeted drug
      delivery systems. 

PMID- 24684477
TI  - Evaluation of a tertiary teledermatology service between peripheral and academic
      dermatologists in the Netherlands.
AB  - BACKGROUND: Tertiary teledermatology (TTD)-secondary-care to tertiary-care
      teleconsultation-is applied rarely compared with the frequently applied secondary
      teledermatology (primary to secondary care). The objective of this study was to
      determine the effect of TTD on referrals from peripheral dermatologists to the
      tertiary center and to evaluate acceptance of TTD. MATERIALS AND METHODS: From
      May 2010 to May 2012, 39 dermatologists could send in teleconsultations to one of
      two tertiary centers. Physical referrals to the tertiary centers prevented by TTD
      were calculated based on questions before and after TTD. The acceptance of the
      TTD system was evaluated through questionnaires, a focus group meeting, and
      personal interviews. RESULTS: Eighty-five teleconsultations were sent by 13
      peripheral dermatologists from nine care institutions and answered by 8 tertiary
      dermatologists. Of the patients, 62% (n=53) would have been referred physically
      to the tertiary center if teledermatology were not available. In this group,
      teledermatology prevented 81% (n=43) of physical referrals. Dermatologists
      indicated that TTD had important advantages such as fast response time,
      formalized records, and data and privacy security. However, the current work
      process using telephone and e-mail was preferred because of its ease of use and
      direct personal network. The following conditions that could lead to successful
      implementation were indicated: (1) a national TTD system including all
      dermatologists indexed according their subspecialty, (2) ability to send the TTD
      consultation to a dermatologist personally, (3) ability to discuss a case with
      multiple dermatologists, (4) connections to electronic health records, and (5)
      change in policies of tertiary centers or health insurers, where they would
      stimulate the use of TTD consultation for all referrals and questions.
      CONCLUSIONS: Although quantitative results indicate that TTD can be used to
      improve triage between secondary and tertiary centers and dermatologists
      perceived advantages of TTD, the motivation to use TTD in this setting was
      lacking as current work processes were easier to use.

PMID- 24684478
TI  - Home telehealth for chronic disease management: selected findings of a narrative
      synthesis.
AB  - BACKGROUND: Chronic disease has become an increasingly important issue for
      individuals and healthcare organizations across Canada. Home telehealth may have
      the potential to alleviate the economic and social challenges associated with
      rising rates of chronic disease. An aim of this review was to gather and
      synthesize the evidence on the effectiveness of home telehealth in chronic
      disease management. MATERIALS AND METHODS: We searched the Medline, EMBASE, Web
      of Science, CINAHL, and PAIS databases for studies published in English from
      January 1, 2005, and December 31, 2010. Academic publications, white papers, and
      gray literature were all considered eligible for inclusion, provided an original
      research element was present. Articles were screened for relevance. RESULTS: One
      hundred one articles on quantitative or mixed-methods studies reported the
      effects of home telehealth on disease state, symptoms, and quality of life in
      chronic disease patients. Studies were consistent in finding that home telehealth
      was equivalent or superior to usual care. CONCLUSIONS: The literature strongly
      supports the use of home telehealth as an equally effective alternative to usual
      care. The circumstances under which home telehealth emerges as significantly
      better than usual care have not been extensively researched. Further research
      into factors affecting the effectiveness of home telehealth would support more
      widespread realization of telehealth's potential benefits.

PMID- 24684479
TI  - District nurses' lived experiences of meeting significant others in advanced home
      care.
AB  - AIM: The aim of this study was to illuminate the meanings of district nurses'
      lived experiences of meeting significant others in the home when giving advanced
      home care to patients. METHODS: The data was collected through 10 audio-taped
      narrative focus-group interviews with 36 district nurses and interpreted using a
      phenomenological hermeneutic approach. FINDINGS: Three themes emerged. The first
      theme, Feeling close, consists of three subthemes: Being available, Sharing
      understanding and Being aware. The second theme, Mediating strength, contains the
      subthemes Being a resource and Sharing trust. Being emotionally influenced is the
      third theme and involves the subthemes Experiencing emotional distress and
      Experiencing emotional gratitude. CONCLUSION: Meeting significant others as a
      district nurse in advanced home care means creating and maintaining a trustful
      relationship with significant others, both on a personal and family level, aiming
      to illuminate and respond to their needs and desires. The district nurses strive
      to reach a mutual understanding and co-operate to mediate support. Being a
      district nurse in advanced home care is both emotionally demanding and
      emotionally rewarding.

PMID- 24684480
TI  - Dual method use among a sample of first-year college women.
AB  - CONTEXT: Dual method use-using one protective method to reduce the risk of STDs
      and another to prevent pregnancy-is effective but understudied. No prior studies
      have employed an event-level approach to examining characteristics associated
      with dual method use among college women. METHODS: In 12 consecutive monthly
      surveys conducted in 2009-2010, data on 1,843 vaginal intercourse events were
      collected from 296 first-year college women. Women reported on their use of
      condoms and hormonal contraceptives during all events. Multilevel regression
      analysis was used to assess associations between event-, month- and person-level
      characteristics and hormonal use and dual method use. RESULTS: Women used
      hormonal contraceptives during 53% of events and condoms during 63%. Dual method
      use was reported 28% of the time, and only 14% of participants were consistent
      users of dual methods. The likelihood of dual method use was elevated when sex
      partners were friends as opposed to romantic partners or ex-boyfriends (odds
      ratios, 2.5-2.8), and among women who had received an STD diagnosis prior to
      college (coefficient, 2.9); it also increased with level of religiosity (0.8).
      Dual use was less likely when less reliable methods were used (odds ratio, 0.2)
      and when women reported more months of hormonal use (0.8), were older than 18
      (coefficient, -4.7) and had had a greater number of partners before college (
      0.3). CONCLUSIONS: A better understanding of the characteristics associated with
      dual method use may help in the design of potential intervention efforts.

PMID- 24684482
TI  - Notch1 increases Snail expression under high reactive oxygen species conditions
      in hepatocellular carcinoma cells.
AB  - Notch1 and reactive oxygen species (ROS) modulate important pathways associated
      with tumor development and progression. Notably, Notch1 expression is upregulated
      in 41.8% of hepatocellular carcinoma (HCC) patients and ROS levels increases as
      HCC progresses from Grade I to Grade III. It has been established that Notch1 and
      ROS modulate Snail expression in malignant tumors; however, the mechanism
      regulating Snail protein expression is not yet known. In this study, we observed
      that Notch1 and ROS cooperatively increase the levels of Snail protein in Huh7
      (hepatoma) cells. On its own, signaling through Notch1 increases transcription of
      Snail without changing protein levels. In contrast, the combined activation of
      the Notch1 and ROS-induced phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling
      pathways resulted in the high expression of Snail protein. This increase in Snail
      expression was associated with increased Huh7 cells invasiveness. Furthermore, we
      observed that correlation between Snail and Notch1 expression was the strongest
      in advanced grade HCC tissue. In conclusion, Notch1 and ROS-induced PI3K/Akt
      signals cooperatively increase Snail expression and may induce malignancy in HCC.

PMID- 24684481
TI  - Detection of lipoarabinomannan in urine for identification of active tuberculosis
      among HIV-positive adults in Ethiopian health centres.
AB  - OBJECTIVE: To assess the diagnostic performance of urine lipoarabinomannan (LAM)
      detection for TB screening in HIV-positive adults in Ethiopia. METHODS: Testing
      for LAM was performed using the Determine TB-LAM lateral flow assay on urine
      samples from participants in a prospective cohort with baseline bacteriological
      categorisation for active TB in sputum. Characteristics of TB patients with
      regard to LAM status were determined. Participants were followed for 6 months to
      evaluate survival, retention in care and incident TB. RESULTS: Positive LAM
      results were found in 78/757 participants. Among 128 subjects with definite
      (confirmed by culture and/or Xpert MTB/RIF) TB, 33 were LAM-positive (25.8%); the
      respective figure for clinically diagnosed cases was 2/20 (10%). Five of the
      remaining 43 LAM-positive individuals had died during the 6-month follow-up
      period, whereas 38 remained in care without clinical signs of TB. The overall
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients,
      LAM positivity was associated with higher WHO clinical stage, lower body mass
      index (BMI), CD4 cell and haemoglobin levels, and with increased mortality. A
      combination algorithm of urine LAM testing and sputum smear microscopy detected
      49 (38.2%) of definite TB cases; among those with CD4 count <=100 cells/mm3 ,
      this proportion was 66.7%. CONCLUSIONS: The performance of urine LAM testing for
      TB detection was poor in this population. However, this was improved among
      subjects with CD4 count <=100 cells/mm3 . In combination with sputum microscopy
      urine, LAM could be considered for targeted TB screening in this subgroup.

PMID- 24684483
TI  - Impact of the International Continence Society (ICS) report on the
      standardisation of terminology in nocturia on the quality of reports on nocturia
      and nocturnal polyuria: a systematic review.
AB  - OBJECTIVE: To systematically review and evaluate the impact of the International
      Continence Society (ICS)-2002 report on standardisation of terminology in
      nocturia, on publications reporting on nocturia and nocturnal polyuria (NP). In
      2002, the ICS defined NP as a Nocturnal Polyuria Index (nocturnal urine
      volume/total 24-h urine volume) of >0.2-0.33, depending on age. MATERIALS AND
      METHODS: In April 2013 the PubMed and Embase databases were searched for studies
      (in English, German, French or Dutch) based on original data and adult
      participants, investigating the relationship between nocturia and NP. A
      methodological quality assessment was performed, including scores on external
      validity, internal validity and informativeness. Quality scores of items were
      compared between studies published before and after the ICS-2002 report. RESULTS:
      The search yielded 78 publications based on 66 studies. Quality scores of studies
      were generally high for internal validity (median 5, interquartile range [IQR] 4
      6) but low for external validity. After publication of the ICS-2002 report,
      external validity showed a significant change from 1 (IQR 1-2) to 2 (IQR 1-2.5; P
      = 0.019). Nocturia remained undefined in 12 studies. In all, 19 different
      definitions were used for NP, most often being the ICS (or similar) definition:
      this covered 52% (n = 11) of studies before and 66% (n = 27) after the ICS-2002
      report. Clear definitions of both nocturia and NP were identified in 67% and 76%
      before, and in 88% and 88% of the studies after the ICS-2002 report,
      respectively. CONCLUSION: The ICS-2002 report on standardisation of terminology
      in nocturia appears to have had a beneficial impact on reporting definitions of
      nocturia and NP, enabling better interpretation of results and comparisons
      between research projects. Because the external validity of most of the 66
      studies is considered a problem, the results of these studies may not be validly
      extrapolated to other populations. The ICS definition of NP is used most often.
      However, its discriminative value seems limited due to the estimated difference
      of 0.6 nocturnal voids between individuals with and without NP. Refinement of
      current definitions based on robust research is required. Based on
      pathophysiological reasoning, we argue that it may be more appropriate to define
      NP based on nocturnal urine production or nocturnal voided volumes, rather than
      on a diurnal urine production pattern.

PMID- 24684484
TI  - Craniosynostosis surgery in an infant with a complex cyanotic cardiac defect.
AB  - We report on a case where craniosynostosis surgery for a left-sided coronal
      synostosis was performed successfully on an 11-month old infant with a
      hypoplastic left ventricle with a dysplastic mitral valve, double outlet right
      ventricle, transposition of the great arteries, atrial septal defect, multiple
      ventricular septal defects, and surgically applied pulmonary banding.
      Craniosynostosis surgery is considered high-risk surgery, because of possible
      sudden and extensive blood loss, and is usually performed in cardiopulmonary
      healthy children. Children with congenital heart disease undergoing noncardiac
      surgery have an increased risk of perioperative morbidity and cardiac arrest.
      Patients with hypoplastic left heart syndrome are a high-risk population when
      undergoing noncardiac surgery, in all stages of palliation. This infant would be
      undergoing a partial cavo-pulmonary connection (PCPC) within a few months. With a
      PCPC, drainage of cranial vessels is dependent on passive flow via the superior
      caval vein directly into the pulmonary artery. Consequently, this could lead to
      an increased blood loss during craniosynostosis surgery. Therefore, it was
      decided to perform the craniosynostosis surgery first, before establishing a
      PCPC. When a child with CHD presents for high-risk noncardiac surgery, future
      cardiac procedures and physiology also have to be taken into account. A
      multidisciplinary approach, involving pediatric cardiologists and pediatric
      anesthesiologists, is essential in making this decision. 

PMID- 24684485
TI  - Seagrass feeding choices and digestive strategies of the herbivorous fish Sarpa
      salpa.
AB  - This is the first study investigating the plant-herbivore interaction between
      Sarpa salpa, which has overgrazed seagrass transplants in Portugal, and the
      seagrasses Cymodocea nodosa, Zostera marina and Zostera noltii, which have been
      considered for restoration. When offered the choice between the three seagrasses
      in outdoor tanks, adult S. salpa clearly preferred Z. noltii. Testing the
      seagrasses separately, mean +/- s.d. feeding rates ranged from 21 +/- 11 g
      seagrass fresh mass kg-1 fish mass day-1 for Z. marina to 32 +/- 9 g seagrass
      fresh mass kg-1 fish mass day-1 for C. nodosa and 40 +/- 11 g seagrass fresh mass
      kg-1 fish mass day-1 for Z. noltii (temperature = 16 degrees  C). Food-processing
      rate in S. salpa did not differ between seagrasses, and there was no evidence of
      a regulation of processing rate according to food intake. Seagrasses differed
      substantially in nitrogen content and C:N, with C. nodosa containing the highest
      nitrogen content and lowest C:N (2.5 +/- 0.1% and 14.0 +/- 1.0), followed by Z.
      noltii (2.1 +/- 0.1% and 17.0 +/- 1.0) and Z. marina (1.4 +/- 0.1% and 26.0 +/-
      2.0). Food-processing rate in S. salpa and the nutritional value of the
      seagrasses were not correlated with the observed feeding preference and rate. The
      study suggests that C. nodosa and Z. marina are less at risk of overgrazing by S.
      salpa and might thus be preferable to Z. noltii for seagrass restoration in areas
      with noticeable abundances of this fish.

PMID- 24684486
TI  - Influence of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration
      of dental implants in rabbit calvaria.
AB  - AIM: Until recently, adverse effects of non-steroidal anti-inflammatory drugs
      (NSAIDs) on osseointegration of dental implants were unknown. Hence, this study
      investigated the short- and long-term effects of a 7-day regimen of parecoxib and
      diclofenac sodium on osseointegration of dental implants in calvarial bone.
      MATERIAL AND METHODS: Eighteen New Zealand White rabbits were randomly allocated
      into three groups (each n = 6): Control group with no postoperative pain killers
      (Group A), diclofenac group (Group B) and parecoxib group (Group C). In each
      animal, one dental implant was placed into the calvarial bone (total n = 18).
      Three rabbits from each group were sacrificed in Week 4. The other three rabbits
      from each group were sacrificed in Week 12 postoperatively. The implant together
      with the calvarial bone and dura mater was harvested and subjected to micro
      computed tomography (micro-CT) and histomorphometric analysis. RESULTS:
      Quantitative analysis of micro-CT data and histomorphometric data neither
      revealed any statistically significant (P <= 0.05) differences between the three
      different groups related to osseointegration nor between different time points of
      observation. CONCLUSION: In rabbits, a 7-day regimen of appropriate doses of
      diclofenac sodium and parecoxib did not adversely affect osseointegration of
      dental implants and bone healing in calvaria, neither short nor long term (12
      weeks).

PMID- 24684487
TI  - Emissions and climate-relevant optical properties of pollutants emitted from a
      three-stone fire and the Berkeley-Darfur stove tested under laboratory
      conditions.
AB  - Cooking in the developing world generates pollutants that endanger the health of
      billions of people and contribute to climate change. This study quantified
      pollutants emitted when cooking with a three-stone fire (TSF) and the Berkeley
      Darfur Stove (BDS), the latter of which encloses the fire to increase fuel
      efficiency. The stoves were operated at the Lawrence Berkeley National Laboratory
      testing facility with a narrow range of fuel feed rates to minimize performance
      variability. Fast (1 Hz) measurements of pollutants enabled discrimination
      between the stoves' emission profiles and development of woodsmoke-specific
      calibrations for the aethalometer (black carbon, BC) and DustTrak (fine
      particles, PM2.5). The BDS used 65+/-5% (average+/-95% confidence interval) of
      the wood consumed by the TSF and emitted 50+/-5% of the carbon monoxide emitted
      by the TSF for an equivalent cooking task, indicating its higher thermal
      efficiency and a modest improvement in combustion efficiency. The BDS reduced
      total PM2.5 by 50% but achieved only a 30% reduction in BC emissions. The BDS
      emitted particles were, therefore, more sunlight-absorbing: the average single
      scattering albedo at 532 nm was 0.36 for the BDS and 0.47 for the TSF. Mass
      emissions of PM2.5 and BC varied more than emissions of CO and wood consumption
      over all tests, and emissions and wood consumption varied more among TSF than BDS
      tests. The international community and the Global Alliance for Clean Cookstoves
      have proposed performance targets for the highest tier of cookstoves that
      correspond to greater reductions in fuel consumption and PM2.5 emissions of
      approximately 65% and 95%, respectively, compared to baseline cooking with the
      TSF. Given the accompanying decrease in BC emissions for stoves that achieve this
      stretch goal and BC's extremely high global warming potential, the short-term
      climate change mitigation from avoided BC emissions could exceed that from
      avoided CO2 emissions.

PMID- 24684488
TI  - Heparin removal from human plasma using molecular imprinted cryogels.
AB  - In this study, heparin-imprinted poly(hydroxyethyl methacrylate-N-[(3
      dimethylamino)-propyl] methacrylamide) cryogel column (HpMIP) was synthesized for
      removal of Hp from human plasma using molecular imprinting technique. Hp removal
      studies were performed from both aqueous solution and human plasma. Selectivity
      studies were performed using fast protein liquid chromatography (FPLC) system.
      The obtained results showed that the HpMIP column can remove Hp from both aqueous
      solutions and human plasma samples selectively. Ninety per cent of Hp was removed
      from 28 U/mL of human plasma samples successfully. Non-imprinted cryogel column
      (NIP) and plane PHEMA column were also synthesized to compare selectivity and non
      specific adsorption properties. 

PMID- 24684489
TI  - Simulation and verification of macroscopic isotropy of hollow alginate-based
      microfibers.
AB  - A simulation of tensile strength of various alginate-based hollow microfibers
      using FEA analysis has been conducted with the hypothesis of macroscopic isotropy
      and linear elastic-plastic behavior. Results of student t-tests indicated that
      there was no significant difference between the experimental and simulated
      tensile strengths (p = 0.37, alpha = 0.05), while there was a significant
      reduction in elasticity as a result of chitosan coating (p = 0.024, alpha =
      0.05). The hypothesis of macroscopic isotropy was verified by highly correlated
      (R(2) >= 0.92) theoretical and experimental elongation at break measurements,
      findings that could be extended to the failure analysis of alginate microfibers
      used in regenerative medicine. 

PMID- 24684490
TI  - Sonication-assisted drug encapsulation in layer-by-layer self-assembled gelatin
      poly (styrenesulfonate) polyelectrolyte nanocapsules: process optimization.
AB  - We report the development of Layer-by-Layer (LbL) polyelectrolyte self-assembled
      nanocrystalline drug-delivery platform using two experimental factors, namely the
      number of coatings and temperature during deposition with three varying levels.
      The optimized formulation (Fopt) was assessed for zeta potential and particle
      size using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning
      Calorimetry (DSC), and Scanning Electron Microscopy (SEM). Charge reversal along
      with an increase in particle size confirmed coating of polyelectrolyte on drug
      nanocrystals. The FT-IR study revealed no signs of incompatibility or change in
      formulation property during preformulation and stability study. This fact was
      further supported by DSC results. 

PMID- 24684491
TI  - Gold-catalyzed enantioselective ring-expanding cycloisomerization of
      cyclopropylidene bearing 1,5-enynes.
AB  - An enantioselective ring-expanding cycloisomerization of 1,5-enynes bearing a
      cyclopropylidene moiety has been developed. This methodology provides a new
      approach to bicyclo[4.2.0]octanes, a structural motif present in many
      biologically active natural products. 

PMID- 24684492
TI  - Association of nitric oxide synthase 3 (NOS3) 894 G>T polymorphism with
      prognostic outcomes of anthracycline in Chinese patients with acute myeloid
      leukaemia.
AB  - The aim of the present study was to investigate the influence of the nitric oxide
      synthase 3 (NOS3) 894 G>T polymorphism on prognostic outcomes of anthracycline in
      Chinese patients with de novo intermediate-risk acute myeloid leukaemia (AML) and
      to examine the gene expression level in relation to genetic variation. In all,
      225 Chinese patients with intermediate-risk AML (at the complete remission stage)
      treated with anthracycline were enrolled in the study. The 894 G>T polymorphism
      of the NOS3 gene was analysed by allele-specific matrix-assisted laser desorption
      ionization time-of-flight. Expression of NOS3 mRNA was tested in 72 patients of
      known genotype for NOS3 894 G>T. The clinical characteristics of these patients
      were obtained from medical records. Survival analysis showed that patients with
      AML (GG genotype) had a longer overall survival (OS; P = 0.006). After adjusting
      for age, gender, leucocyte count, haemoglobin level, platelet level, French,
      American and Britain (FAB) classification, lactate dehydrogenase levels, Eastern
      Cooperative Oncology Group Performance Status, nucleophosmin gene and fms-related
      tyrosine kinase 3 gene, multivariate survival analysis showed that the NOS3 894
      G>T polymorphism appeared to be a predicting factor for OS (P = 0.014; hazard
      ratio = 1.856). However, no significant associations between the NOS3 894 G>T
      polymorphism and relapse-free survival and relapse in patients with AML were
      observed. Gene expression levels were significantly higher in patients with the
      GG genotype than in patients with the GT and TT genotypes (P = 0.033). The
      findings suggest that the NOS3 894 G>T variant may be a biomarker for the
      prediction of OS in Chinese patients with AML. 

PMID- 24684493
TI  - Studies on deacetoxycephalosporin C synthase support a consensus mechanism for 2
      oxoglutarate dependent oxygenases.
AB  - Deacetoxycephalosporin C synthase (DAOCS) catalyzes the oxidative ring expansion
      of penicillin N (penN) to give deacetoxycephalosporin C (DAOC), which is the
      committed step in the biosynthesis of the clinically important cephalosporin
      antibiotics. DAOCS belongs to the family of non-heme iron(II) and 2-oxoglutarate
      (2OG) dependent oxygenases, which have substantially conserved active sites and
      are proposed to employ a consensus mechanism proceeding via formation of an
      enzyme.Fe(II).2OG.substrate ternary complex. Previously reported kinetic and
      crystallographic studies led to the proposal of an unusual "ping-pong" mechanism
      for DAOCS, which was significantly different from other members of the 2OG
      oxygenase superfamily. Here we report pre-steady-state kinetics and binding
      studies employing mass spectrometry and NMR on the DAOCS-catalyzed penN ring
      expansion that demonstrate the viability of ternary complex formation in DAOCS
      catalysis, arguing for the generality of the proposed consensus mechanism for 2OG
      oxygenases. 

PMID- 24684494
TI  - Thermally induced structural evolution and performance of mesoporous block
      copolymer-directed alumina perovskite solar cells.
AB  - Structure control in solution-processed hybrid perovskites is crucial to design
      and fabricate highly efficient solar cells. Here, we utilize in situ grazing
      incidence wide-angle X-ray scattering and scanning electron microscopy to
      investigate the structural evolution and film morphologies of methylammonium lead
      tri-iodide/chloride (CH3NH3PbI(3-x)Cl(x)) in mesoporous block copolymer derived
      alumina superstructures during thermal annealing. We show the CH3NH3PbI(3-x)Cl(x)
      material evolution to be characterized by three distinct structures: a
      crystalline precursor structure not described previously, a 3D perovskite
      structure, and a mixture of compounds resulting from degradation. Finally, we
      demonstrate how understanding the processing parameters provides the foundation
      needed for optimal perovskite film morphology and coverage, leading to enhanced
      block copolymer-directed perovskite solar cell performance.

PMID- 24684495
TI  - Asymmetric synthesis of protected alpha-amino boronic acid derivatives with an
      air- and moisture-stable Cu(II) catalyst.
AB  - The asymmetric borylation of N-tert-butanesulfinyl imines with
      bis(pinacolato)diboron is achieved using a Cu(II) catalyst and provides access to
      synthetically useful and pharmaceutically relevant alpha-amino boronic acid
      derivatives. The Cu(II)-catalyzed reaction is performed on the benchtop in air at
      room temperature using commercially available, inexpensive reagents at low
      catalyst loadings. A variety of N-tert-butanesulfinyl imines, including
      ketimines, react readily to provide alpha-sulfinamido boronate esters in good
      yields and with high stereoselectivity. In addition, this transformation is
      applied to the straightforward, telescoped synthesis of alpha-sulfinamido
      trifluoroborates.

PMID- 24684496
TI  - Facial reconstruction surgery 10 years after treatment for hemangiopericytoma:
      planning considerations and clinical outcomes.
AB  - This paper describes the surgical correction of ankylosis of the right
      temporomandibular joint and reconstruction of the middle and lower thirds of the
      right side of the face in a young man who had undergone treatment for
      hemangiopericytoma 10 years earlier, which led to serious functional, esthetic,
      and psychological problems and diminished his quality of life. The results of
      reconstruction surgery with alloplastic material (Medopor(r)) and surgical
      planning with fibrotic tissue due to radiation and the risk of osteoradionecrosis
      are discussed.

PMID- 24684497
TI  - Barriers to accessing HIV-prevention in clinic settings: Higher alcohol use and
      more sex partners predict decreased exposure to HIV-prevention counseling.
AB  - Understanding barriers to accepting HIV-prevention counseling among vulnerable
      populations is of critical importance, as prevention efforts can only have a
      public health impact if high-risk populations are willing to enroll. A
      correlational field study was conducted in a health care setting with a high-risk
      community sample (N = 350) to determine if number of sex partners and alcohol
      consumption predict acceptance of an invitation to take part in HIV-prevention
      counseling. Findings indicated that participants engaging in the least risky
      behavior (i.e. individuals reporting no alcohol consumption and few sex partners)
      were more likely to accept an offer to receive HIV-prevention counseling.
      Moreover, heavy drinking was associated with decreased exposure to HIV-prevention
      counseling, regardless of the number of sex partners reported (b = .12, p > .05).
      Given associations between heavy drinking and sexual risk taking, finding ways to
      increase exposure to HIV-prevention counseling programs among heavy drinkers
      could serve a vital public health function.

PMID- 24684498
TI  - The target effect: visual memory for unnamed search targets.
AB  - Search targets are typically remembered much better than other objects even when
      they are viewed for less time. However, targets have two advantages that other
      objects in search displays do not have: They are identified categorically before
      the search, and finding them represents the goal of the search task. The current
      research investigated the contributions of both of these types of information to
      the long-term visual memory representations of search targets. Participants
      completed either a predefined search or a unique-object search in which targets
      were not defined with specific categorical labels before searching. Subsequent
      memory results indicated that search target memory was better than distractor
      memory even following ambiguously defined searches and when the distractors were
      viewed significantly longer. Superior target memory appears to result from a
      qualitatively different representation from those of distractor objects,
      indicating that decision processes influence visual memory. 

PMID- 24684499
TI  - Efficiency of microbial phytase supplementation in diets formulated with
      different calcium:phosphorus ratios, supplied to broilers from 22 to 33 days old.
AB  - An experiment was conducted with broilers from 22 to 33 days of age to evaluate
      the efficiency of six microbial phytases supplemented in diets (1500 FTU/kg) that
      were formulated with three different calcium:available phosphorus (Ca:P(avail))
      ratios (4.5:1.0, 6.0:1.0 and 7.5:1.0). A positive control diet without phytase
      was formulated with a Ca:P(avail) ratio of 7.5:3.4 to meet the nutritional
      requirements of the broilers. The P and ash contents of the tibia, magnesium in
      the plasma, performance, balance and retention of phytate phosphorus (P(phyt)),
      intake of total P and nitrogen (N), nitrogen-corrected apparent metabolizable
      energy and apparent digestibility of dry matter of the diets were not influenced
      (p > 0.05) by the type of phytase or the dietary Ca:P(avail) ratio. However,
      there was an interaction (p < 0.05) between the phytase type and the Ca:P(avail)
      ratio for the retention coefficients of total P, Ca and N. Phytase B resulted in
      the highest Ca deposition in the tibia (p < 0.01). Phytases D, E and F reduced
      the Ca concentrations in the tibia (p < 0.01) and plasma (p < 0.05). Phytase D
      increased the P level in the plasma and decreased the total P excretion (p <
      0.01). Phytases E and F increased Ca excretion, while phytase A reduced it (p <
      0.01). Regardless of the phytase type, increasing the dietary Ca:P(avail) ratio
      reduced (p < 0.05) the plasma P concentration and the excretion of total P and N
      and, conversely, increased (p < 0.05) the plasma concentration, intake and
      excretion of Ca. For the rearing period evaluated, it is possible to reduce the
      P(avail) of the diet to 1.0 g/kg when Ca is maintained at 7.5 g/kg, and the diet
      is supplemented with 1500 FTU of phytase A, C, D or E/kg. This diet allows the
      maintenance of performance and adequate bone mineralization, and it improves the
      Ca, total P and P(phyt) utilization in addition to reducing the excretion of N
      and P into the environment.

PMID- 24684501
TI  - Enhanced air stability of polymer solar cells with a nanofibril-based photoactive
      layer.
AB  - In spite of the rapid increase in the power conversion efficiency (PCE) of
      polymer solar cells (PSCs), the poor stability of the photoactive layer in air
      under sunlight is a critical problem blocking commercialization of PSCs. This
      study investigates the photo-oxidation behavior of a bulk-heterojunction (BHJ)
      photoactive film made of single-crystalline poly(3-hexlythiophene) (P3HT)
      nanofibrils and fullerene derivatives [phenyl-C61-butyric methyl ester (PCBM),
      indene-C 60 bisadduct (ICBA)]. Because the single-crystalline P3HT nanofibrils
      had tightly packed pi-pi stacking, the permeation of oxygen and water into the
      nanofibrils was significantly reduced. Chemical changes in P3HT were not apparent
      in the nanofibrils, and hence the air stability of the nanofibril-based BHJ film
      was considerably enhanced as compared with conventional BHJ films. The chemical
      changes were monitored by Fourier-transform infrared (FT-IR) spectroscopy, Raman
      spectroscopy, and UV-vis absorbance. Inverted PSCs made of the nanofibril-based
      BHJ layer also showed significantly enhanced air stability under sunlight. The
      nanofibril-based solar cell maintained more than 80% of its initial PCE after 30
      days of continuous exposure to sunlight (AM 1.5G, 100 mW/cm(2)), whereas the PCE
      of the conventional BHJ solar cell decreased to 20% of its initial PCE under the
      same experimental conditions. 

PMID- 24684500
TI  - Ameliorative effect of Pimpinella anisum oil on immunohistochemical and
      ultrastuctural changes of cerebellum of albino rats induced by aspartame.
AB  - The study aims to investigate the protective effect of Pimpinella anisum oil on
      aspartame (ASP) which resulted in cerebellar changes. The rats were divided into
      four equal groups: Group 1: (control group): served as control animals. Group 2:
      control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group):
      received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given
      orally to the animals by intra-gastric tube for 2 months. Group 4: received .5
      mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h
      for 2 months. The histopathological approach revealed marked changes in the
      Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated
      animals. Some of these cells appeared with deeply stained cytoplasm.
      Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic
      reticulum and condensed mitochondria. Granular cells appeared with less c nuclei
      and surrounded by dissolution of most Mossy rosettes structures. Most myelinated
      nerve fibers showed thickening of myelinated sheath and others showed splitting
      of their myelin sheath. The histopathological, immunohistochemical and
      ultrastructural alterations were much less observed in concomitant use of P.
      anisum oil with ASP. Cerebellar cortex is considered target areas of ASP
      neurotoxicity, while P. anisum oil, when used in combination with ASP displays a
      protective action against neurotoxicity.

PMID- 24684502
TI  - Exploring the genetic underpinnings of brain and behavioral disorders.

PMID- 24684503
TI  - Three new vibralactone-related compounds from cultures of Basidiomycete
      Boreostereum vibrans.
AB  - Three new compounds, named as vibralactones K-M (1-3), together with vibralactone
      (4) have been isolated from cultures of the Basidiomycete Boreostereum vibrans.
      Their structures were determined on the basis of spectroscopic evidences (1D and
      2D NMR, HRMS, UV, and IR data), chemical methods and literature data. None of the
      compounds was cytotoxic against five human cancer cell lines and showed
      inhibitory activity on the pancreatic lipase. 

PMID- 24684504
TI  - Silicon nitride grids are compatible with correlative negative staining electron
      microscopy and tip-enhanced Raman spectroscopy for use in the detection of micro
      organisms.
AB  - AIMS: Successive application of negative staining transmission electron
      microscopy (TEM) and tip-enhanced Raman spectroscopy (TERS) is a new correlative
      approach that could be used to rapidly and specifically detect and identify
      single pathogens including bioterrorism-relevant viruses in complex samples. Our
      objective is to evaluate the TERS-compatibility of commonly used electron
      microscopy (EM) grids (sample supports), chemicals and negative staining
      techniques and, if required, to devise appropriate alternatives. METHODS AND
      RESULTS: While phosphortungstic acid (PTA) is suitable as a heavy metal stain,
      uranyl acetate, paraformaldehyde in HEPES buffer and alcian blue are unsuitable
      due to their relatively high Raman scattering. Moreover, the low thermal
      stability of the carbon-coated pioloform film on copper grids (pioloform grids)
      negates their utilization. The silicon in the cantilever of the silver-coated
      atomic force microscope tip used to record TERS spectra suggested that Si-based
      grids might be employed as alternatives. From all evaluated Si-based TEM grids,
      the silicon nitride (SiN) grid was found to be best suited, with almost no
      background Raman signals in the relevant spectral range, a low surface roughness
      and good particle adhesion properties that could be further improved by glow
      discharge. CONCLUSIONS: Charged SiN grids have excellent particle adhesion
      properties. The use of these grids in combination with PTA for contrast in the
      TEM is suitable for subsequent analysis by TERS. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study reports fundamental modifications and optimizations of the
      negative staining EM method that allows a combination with near-field Raman
      spectroscopy to acquire a spectroscopic signature from nanoscale biological
      structures. This should facilitate a more precise diagnosis of single viral
      particles and other micro-organisms previously localized and visualized in the
      TEM.

PMID- 24684505
TI  - Long-term tolerance to factor VIII is achieved by administration of interleukin
      2/interleukin-2 monoclonal antibody complexes and low dosages of factor VIII.
AB  - BACKGROUND: Regulatory T cells (Tregs) play a pivotal role in regulating anti
      factor VIII (FVIII) immune responses. Interleukin (IL)-2 mixed with a particular
      IL-2 monoclonal antibody (mAb; JES6-1) can induce the selective expansion of
      Tregs in vivo. METHODS: In the prevention experiments, we treated mice with
      hemophilia A with IL-2/IL-2mAb complexes (three times per week) and concurrently
      with FVIII protein (80 U kg(-1) per week) for 4 weeks. Generation of anti-FVIII
      immune responses was examined afterward. Next, to induce long-term tolerance to
      FVIII, a series of treatment dosages and schedules for administering IL-2/IL-2mAb
      complexes and FVIII protein in mice with hemophilia A was evaluated. RESULTS:
      Compared to control mice that were treated with only FVIII, which produced high
      titer anti-FVIII antibodies, mice treated with IL-2/IL-2mAb complexes plus FVIII
      produced no antibodies. A marked seven-fold increase in CD4(+) CD25(+) Foxp3(+)
      Helios(+) natural Tregs was maintained for 4 weeks in blood, spleen, and lymph
      nodes and then dropped to normal levels within the next 10 days. The suppressive
      functions of expanded Tregs were demonstrated with suppressive, proliferative,
      and cytokine assays. The administration of anti-CD25 mAb (PC-61) blocked this
      protective effect, confirming the involvement of Tregs in suppressing anti-FVIII
      immune responses. Importantly, administration of IL-2/IL-2mAb complexes (three
      times per week for 8 weeks) combined with contiguous weekly injections of low
      dosage FVIII protein (20 U kg(-1) per week for 18 weeks) not only abrogated the
      formation of anti-FVIII antibodies but also induced long-term tolerance to FVIII.
      CONCLUSIONS: Treatment with IL-2/IL-2mAb complexes is highly promising for the
      induction and maintenance of FVIII-specific tolerance after FVIII protein
      replacement therapy.

PMID- 24684506
TI  - Hydrogen sulfide targets EGFR Cys797/Cys798 residues to induce Na(+)/K(+)-ATPase
      endocytosis and inhibition in renal tubular epithelial cells and increase sodium
      excretion in chronic salt-loaded rats.
AB  - AIMS: The role of hydrogen sulfide (H2S) in renal sodium and water homeostasis is
      unknown. We investigated whether H2S promoted Na(+)/K(+)-ATPase endocytosis via
      the H2S/EGFR/gab1/PI3K/Akt pathway in renal tubular epithelial cells. RESULTS:
      H2S decreased Na(+)/K(+)-ATPase activity and induced its endocytosis in renal
      tubular epithelial cells, which was abrogated by small interfering RNA (siRNA)
      knockdown of epidermal growth factor receptor (EGFR) and gab1, a dominant
      negative mutant of Akt and PI3K inhibitors. H2S increased EGFR, gab1, PI3K, and
      Akt phosphorylation in both renal tubular epithelial cells and kidneys of chronic
      salt-loaded rats. These increases were abrogated by siRNA knockdown of EGFR, but
      not of c-Src. Radiolabeled H2S exhibited transient, direct binding to EGFR and
      directly activated EGFR. Some disulfide bonds in EGFR intracellular kinase domain
      were susceptible to H2S-induced cleavage. Mutations of EGFR Cys797 (human) or
      Cys798 (rat) residues increased EGFR activity and prevented H2S-induced
      Na(+)/K(+)-ATPase endocytosis. H2S also inhibited sodium hydrogen exchanger-3
      (NHE3) activity in renal tubular epithelial cells. H2S treatment increased sodium
      excretion in chronic and acute salt-loaded rats and decreased blood pressure in
      chronic salt-loaded rats. INNOVATION AND CONCLUSION: H2S directly targets some
      disulfide bonds in EGFR, which activates the EGFR/gab1/PI3K/Akt pathway and
      subsequent Na(+)/K(+)-ATPase endocytosis and inhibition in renal tubular
      epithelial cells. EGFR Cys797/Cys798 residues are essential for an intrinsic
      inhibitory mechanism and for H2S actions in renal tubular epithelial cells. Other
      pathways, including NHE3, may be involved in mediating the renal effects of H2S.
      Our results reveal a new renal sodium homeostasis mechanism, which may provide
      for novel treatment approaches for diseases related to renal sodium homeostasis
      dysfunction.

PMID- 24684507
TI  - Anterior cruciate ligament injury after more than 20 years. II. Concentric and
      eccentric knee muscle strength.
AB  - The long-term consequences on knee muscle strength some decades after rupture of
      the anterior cruciate ligament (ACL) are not established. The aims of our study
      were to examine peak torque more than 20 years after ACL injury and to compare
      their knee muscle strength to that of healthy controls. We tested 70 individuals
      with unilateral ACL injury 23 +/- 2 years after injury, whereof 33 (21 men) were
      treated with physiotherapy in combination with ACL reconstruction (ACLR ) and 37
      (23 men) with physiotherapy alone (ACLPT ). These were compared with 33 age- and
      gender-matched controls (21 men). A Kin-Com((r)) dynamometer (90 degrees /s) was
      used to measure peak torque in knee flexion and extension in both concentric and
      eccentric contractions. Knee extension peak torque, concentric and eccentric, was
      ~10% lower for the injured leg compared with the non-injured leg for both ACLR (P
      < 0.001; P < 0.001) and ACLPT (P = 0.007; P = 0.002). The ACLPT group also showed
      reduced eccentric knee flexion torque of the injured leg (P = 0.008). The
      strength of the non-injured leg in both ACL groups was equal to that of controls.
      No difference was seen for those with no-or-low degree of knee osteoarthritis
      compared to those with moderate-to-high degree of osteoarthritis. ACL injury may
      lead to a persistent reduction of peak torque in the injured leg, which needs to
      be considered across the lifespan. 

PMID- 24684509
TI  - Rapid growth increases intrinsic predation risk in genetically modified Cyprinus
      carpio: implications for environmental risk.
AB  - The intrinsic effect of feeding regime on survival and predation-induced
      mortality was experimentally tested in genetically modified (GM) Cyprinus carpio
      and wild specimens. The results clearly indicate a knock-on effect of the GH gene
      (gcGH) introduction into the C. carpio genome on their vulnerability to
      predation. The experiments unequivocally showed that it is the genetic nature of
      the C. carpio rather than its size that affects the risk of predation. In
      addition, fed C. carpio were more susceptible to predation risk. Thus, the study
      characterizes the existence of a trade-off between somatic growth and predator
      avoidance performance. Current research in Europe suggests that high uncertainty
      surrounding the potential environmental effects of escapee transgenic fishes into
      the wild is largely due to uncertainty in how the modified gene will be
      expressed. Understanding variables such as the cost of rapid growth on
      antipredator success would prove to be pivotal in setting up sound risk
      assessments for GM fishes and in fully assessing the environmental risk
      associated with GM fish escapees. 

PMID- 24684508
TI  - The emerging era of pharmacogenomics: current successes, future potential, and
      challenges.
AB  - The vast range of genetic diversity contributes to a wonderful array of human
      traits and characteristics. Unfortunately, a consequence of this genetic
      diversity is large variability in drug response between people, meaning that no
      single medication is safe and effective in everyone. The debilitating and
      sometimes deadly consequences of adverse drug reactions (ADRs) are a major and
      unmet problem of modern medicine. Pharmacogenomics can uncover associations
      between genetic variation and drug safety and has the potential to predict ADRs
      in individual patients. Here we review pharmacogenomic successes leading to
      changes in clinical practice, as well as clinical areas probably to be impacted
      by pharmacogenomics in the near future. We also discuss some of the challenges,
      and potential solutions, that remain for the implementation of pharmacogenomic
      testing into clinical practice for the significant improvement of drug safety.

PMID- 24684510
TI  - Mechanical properties of self-assembled Fmoc-diphenylalanine molecular gels.
AB  - We explore the phase diagram and mechanical properties of molecular gels produced
      from mixing water with a dimethyl sulfoxide (DMSO) solution of the aromatic
      dipeptide derivative fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF). Highly
      soluble in DMSO, Fmoc-FF assembles into fibrous networks that form gels upon
      addition of water. At high water concentrations, rigid gels can be formed at Fmoc
      FF concentrations as low as 0.01 wt %. The conditions are established defining
      the Fmoc-FF and water concentrations at which gels are formed. Below the gel
      boundary, the solutions are clear and colorless and have long-term stability.
      Above the gel boundary, gels are formed with increasing rapidity with increasing
      water or Fmoc-FF concentrations. A systematic characterization of the effect of
      Fmoc-FF and water concentrations on the mechanical properties of the gels is
      presented, demonstrating that the elastic behavior of the gels follows a
      specific, robust scaling with Fmoc-FF volume fraction. Furthermore, we
      characterize the kinetics of gelation and demonstrate that these gels are
      reversible in the sense that they can be disrupted mechanically and rebuild
      strength over time. 

PMID- 24684511
TI  - Factors influencing disease progression of prostate cancer under active
      surveillance: a McGill University Health Center cohort.
AB  - OBJECTIVE: To evaluate the clinical and pathological factors influencing the risk
      of disease progression in a cohort of patients with low-intermediate risk
      prostate cancer under active surveillance (AS). PATIENTS AND METHODS: We studied
      300 patients diagnosed between 1992 and 2012 with prostate adenocarcinoma with
      favourable parameters or who refused treatment and were managed with AS. Of
      those, 155 patients with at least one repeat biopsy and no progression criteria
      at the time of the diagnosis were included for statistical analyses. Patients
      were followed every 3-6 months for prostate-specific antigen (PSA) measurement
      and physical examination. Patients were offered repeat prostatic biopsy every
      year. Disease progression was defined as the presence of one or more of the
      following criteria: >= 3 positive cores, >50% of cancer in at least one core, and
      a predominant Gleason pattern of 4. RESULTS: For the 155 patients, the mean (sd)
      age at diagnosis was 67(7) years; the median (interquartile range) follow-up was
      5.4(3.6-9.5) years. Of these, 67, 25, six, and two patients had two, three, four,
      and five repeat biopsies, respectively. At baseline, 11 (7%) patients had a
      Gleason score of 3+4, while the remaining 144 (93%) patients had a Gleason score
      of <= 6. In all, 50 (32.3%) patients had disease progression on repeat biopsies,
      with a median progression-free survival time of 7 years. The rate of disease
      progression decreased after the second repeat biopsy. The 5-year overall survival
      rate was 100%. Having a PSA density (PSAD) of >0.15 ng/mL/mL, >1 positive core,
      and Gleason score >6 at the time of the diagnosis was associated with a
      significantly higher rate of disease progression on univariate analysis (P <
      0.05), while a maximum percentage of cancer in any core of >10% showed a trend
      toward significance for a higher progression rate (P = 0.054). On multivariate
      analysis, only the presence of a PSAD of >0.15 ng/mL/mL remained significant for
      a higher progression rate (P < 0.05). Of the 155 patients, five (3.2%)
      subsequently received radiotherapy, 13 (8.4%) received hormonal therapy, and 13
      (8.4%) underwent radical prostatectomy. CONCLUSION: AS is a suitable management
      option for patients with clinically low-risk prostate cancer. A PSAD of >0.15
      ng/mL/mL is an important predictor for disease progression.

PMID- 24684512
TI  - The Florey turns 50.
AB  - The origins of the Howard Florey Laboratories of Experimental Physiology,
      Department of Physiology, The University of Melbourne, are tied to the ground
      breaking clinical work of Derek A Denton in 1947 and to the investigations of the
      initial scientific team into the control of salt and water balance in health and
      disease over the period 1947-1963 were Professor RD Wright, Drs JR Goding, IR
      McDonald, John P Coghlan, E Marelyn Wintour and John R Blair-West. An Act of
      Parliament in 1971 by the Victorian State Government formally established the
      Institute named after Howard Florey, the Australian Nobel Prize winner who
      isolated penicillin. The Howard Florey Laboratories/Institute quickly became an
      international leader in the scientific areas of the physiological control of body
      fluids and electrolyte balance, especially sodium regulation and the regulation
      of the secretion of aldosterone, the adrenal salt-retaining hormone; the micro
      measurement of hormones, in particular steroids and peptides; instinctive
      ingestive behaviour; fetal fluid regulation; hybridization histochemistry, and
      the hormone relaxin. Subsequently, the senior staff included, inter alia, Bruce
      Scoggins, Richard Weisinger, John McDougall, Brian Oldfield, Michael McKinley,
      Robin McAllen, Hugh Niall, Geoff Tregear and Felix Beck. During the 1990s, an
      explosion occurred in neuroscience and, in 1997, the Board made the strategic
      decision to change the focus of the Institute to brain disorders. From 1997 to
      2007, Fred Mendelsohn steered the Florey to become one of Australia's premier
      brain research institutes and, under the current director (the eminent clinician
      and neuroscientist Geoffrey Donnan), this reputation has been further enhanced. 

PMID- 24684513
TI  - Synthesis of alpha-diketones from alkylaryl- and diarylalkynes using mercuric
      salts.
AB  - Both alkylarylalkynes and diarylalkynes 1 are converted into the alpha-diketones
      2 in good yield by the use of mercuric salts, e.g., mercuric nitrate hydrate or
      mercuric triflate, in the presence of water. Other mercuric salts, e.g., sulfate,
      chloride, acetate, or trifluoroacetate, do not provide the diketone product. A
      possible mechanism is proposed. 

PMID- 24684514
TI  - Should all patients be optimized to the same preoperative hemoglobin level to
      avoid transfusion in primary knee arthroplasty?
AB  - BACKGROUND AND OBJECTIVE: Optimization of the preoperative hemoglobin (Hb) level
      is an effective way to reduce allogeneic transfusion in total knee arthroplasty
      (TKA) though the procedure is expensive, requires close monitoring and is often
      inconvenient for patients with reduced mobility. Our aim was to investigate the
      value of preoperative Hb levels to predict transfusion and thereby tailoring Hb
      optimization to patient characteristics. MATERIALS AND METHODS: All consecutive
      patients who undergone primary TKA in our center over 2 years, and received
      tranexamic acid intraoperatively, were reviewed. The adjusted association between
      preoperative Hb levels and transfusion was assessed by multivariate logistic
      regression, and the estimated probability of transfusion for individual patients
      was derived from the logistic model. RESULTS: Out of the 784 patients who meet
      the inclusion criteria, risk of transfusion was associated with poorer
      performance status, as measured by the America Association of Anestesiology (ASA)
      score III/IV (OR: 3.3, P < 0.001) and lower preoperative Hb level (OR 3.8 for
      each g/dl below 13 g/dl; P < 0.001). According to the Hb level, the estimated
      probability of transfusion was 0.03 (range: 0.03-0.64) for ASA I/II patients and
      0.10 (range: 0.10-0.84) for ASA III/IV. CONCLUSION: Not all the patients
      undergoing TKA who receive tranexamic acid need the same preoperative Hb
      optimization target. Two easily available factors, such as the ASA score and the
      Hb level, can help individualize the Hb optimization target.

PMID- 24684515
TI  - Regional variation in water-related impacts of shale gas development and
      implications for emerging international plays.
AB  - The unconventional fossil fuel industry is expected to expand dramatically in
      coming decades as conventional reserves wane. Minimizing the environmental
      impacts of this energy transition requires a contextualized understanding of the
      unique regional issues that shale gas development poses. This manuscript
      highlights the variation in regional water issues associated with shale gas
      development in the U.S. and the approaches of various states in mitigating these
      impacts. The manuscript also explores opportunities for emerging international
      shale plays to leverage the diverse experiences of U.S. states in formulating
      development strategies that minimize water-related impacts within their
      environmental, cultural, and political ecosystem. 

PMID- 24684516
TI  - Dissolution chemistry and biocompatibility of single-crystalline silicon
      nanomembranes and associated materials for transient electronics.
AB  - Single-crystalline silicon nanomembranes (Si NMs) represent a critically
      important class of material for high-performance forms of electronics that are
      capable of complete, controlled dissolution when immersed in water and/or
      biofluids, sometimes referred to as a type of "transient" electronics. The
      results reported here include the kinetics of hydrolysis of Si NMs in biofluids
      and various aqueous solutions through a range of relevant pH values, ionic
      concentrations and temperatures, and dependence on dopant types and
      concentrations. In vitro and in vivo investigations of Si NMs and other transient
      electronic materials demonstrate biocompatibility and bioresorption, thereby
      suggesting potential for envisioned applications in active, biodegradable
      electronic implants. 

PMID- 24684517
TI  - IL3 rs40401 polymorphism and interaction with smoking in risk of asthma in
      Japanese women: the Kyushu Okinawa Maternal and Child Health study.
AB  - Three previous genetic association studies conducted in Korea and China
      investigated the relationship between IL3 single nucleotide polymorphism (SNP)
      rs40401 and asthma, but their results were inconsistent. We examined this
      relationship and the possibility of an interaction between IL3 SNP rs40401 and
      smoking in young adult Japanese women. Included were 89 women who met the
      criteria of the European Community Respiratory Health Survey (ECRHS) for asthma.
      Control subjects were 700 women without asthma according to the ECRHS criteria
      who had not been diagnosed with asthma and/or allergic rhinitis by a doctor
      and/or who had not met the criteria of the International Study of Asthma and
      Allergies in Childhood for rhinoconjunctivitis. A significant positive
      association was found between SNP rs40401 and the risk of asthma, with the TT
      genotype as the reference under the additive model: the adjusted odds ratio was
      1.39 (95% CI: 1.004-1.93). The positive association was not statistically
      significant in any other genetic model. Compared with subjects with the TT or TC
      genotype of SNP rs40401 who had never smoked, those with the CC genotype who had
      ever smoked had a significantly increased risk of asthma: the adjusted OR was
      2.67 (95% CI: 1.23-5.79); the additive interaction, but not the multiplicative
      interaction, was significant. This study suggests that IL3 SNP rs40401 is
      significantly associated with the risk of asthma in young adult Japanese women
      and reveals that the combination of ever smoking and having the CC genotype of
      IL3 SNP rs40401 is significantly positively associated with asthma.

PMID- 24684518
TI  - Near-infrared fluorescent 9-phenylethynylpyronin analogues for bioimaging.
AB  - The syntheses and biological applications of two novel fluorescent 9
      phenylethynylpyronin analogues containing either carbon or silicon at the
      position 10 are reported. Both fluorescent probes exhibited a relatively strong
      fluorescence in methanol and phosphate buffer saline in the near-infrared region
      (705-738 nm) upon irradiation of either of their absorption maxima in the blue
      and red regions. The compounds showed high selectivity toward mitochondria in
      myeloma cells in vivo and allowed their visualization in a favored tissue
      transparent window, which makes them promising NIR fluorescent tags for
      applications in bioimaging.

PMID- 24684519
TI  - Histology of a novel injectable filler (polymethylmethacrylate and cross-linked
      dextran in hydroxypropyl methylcellulose) in a rat model.
AB  - A novel injectable filler of polymethylmethacrylate (PMMA) and cross-linked
      dextran in hydroxypropyl methylcellulose was introduced in the commercial filler
      market. For soft tissue augmentation, safety and biocompatibility should be
      evaluated and the stability at the implantation site should be assessed using
      histologic evaluation. In order to evaluate the biocompatibility of the novel
      soft tissue filler, PMMA and cross-linked dextran in hydroxypropyl
      methylcellulose was subdermally injected into the skin of Sprague-Dawley Rats.
      Histologic evaluation was performed at 13 weeks and 12 months after the
      injection. Inflammatory cell infiltration, neovascularization, and fibrosis were
      scored according to defined grading systems. The mean score of the histologic
      evaluation was 5.7 and 3.9 at 13 weeks and 12 months, respectively. At 12 months
      after injection, the PMMA and cross-linked dextran in hydroxypropyl
      methylcellulose appeared to be kept in place through fine fibrous capsules. The
      mixture of PMMA and cross-linked dextran in hydroxypropyl methylcellulose can be
      safely applied for soft tissue augmentation with longevity of greater than 12
      months.

PMID- 24684520
TI  - A pilot study examining mindfulness-based cognitive therapy in psoriasis.
AB  - A sub-population of people with psoriasis have strong causal beliefs about
      stress, high levels of emotional distress (anxiety and depression) and an
      impaired quality of life (QoL). Mindfulness-based cognitive therapy has been
      found to reduce levels of stress and distress and to improve QoL. This pilot
      study in people with psoriasis aimed to test the hypothesis that mindfulness
      could reduce stress and thereby lessen psoriasis severity, improve QoL and reduce
      distress. Twenty-nine people with psoriasis (22-70-years old; 16 females; 13
      males) were randomised to an eight-week mindfulness treatment as an adjunct to
      their usual psoriasis therapy or to a control group which continued with usual
      psoriasis therapy alone. All subjects completed self-reported measurements of
      psoriasis severity, perceived stress, distress and QoL, at baseline and again
      post-intervention. The mindfulness group reported statistically lower psoriasis
      severity (Self-Assessed Psoriasis Area Severity Index; z = 1.96, p = .05) and QoL
      impairment scores (Dermatology Life Quality Index; z = 2.30, p = .02) than the
      control group. There was no significant difference between groups on perceived
      stress (Perceived Stress Scale; z = .07, p = .94) or distress scores (Hospital
      Anxiety Depression Scale; z = 1.60, p = .11). People with psoriasis who received
      mindfulness as an adjunct to their usual therapy reported a significant
      improvement in both psoriasis severity and QoL. These pilot results suggest that
      a full randomised control trial is justified to examine the effectiveness of
      mindfulness as an adjunctive treatment for people with psoriasis.

PMID- 24684521
TI  - Relationship of age with the size of the interventricular foramina and aqueductus
      sylvii: a morphometric evaluation.
AB  - OBJECTIVES: The ventricular system is an essential part of the brain. Various
      pathologies directly or indirectly affect the size of this system. Morphometric
      analysis of the cerebral ventricular system is important for evaluating changes
      due to growth, aging, and intrinsic and extrinsic pathologies. The aim of this
      study was to evaluate the normative data for the interventricular foramina and
      cerebral aqueduct with regard to surgery and clinical situations. METHODS:
      Cranial magnetic resonance imaging (MRI) scans of 128 healthy subjects (63 female
      subjects, 65 male subjects; 2-63 years old) were individually reviewed. The right
      and left interventricular foramina lengths and diameters and the cerebral
      aqueduct length and diameter were statistically evaluated and compared between
      sexes and among age groups. RESULTS: There were no significant differences among
      the age groups in either sex (P > 0.05). Additionally, there was no correlation
      between age and measurement parameters (P > 0.05). DISCUSSION: We did not observe
      any changes in interventricular foramina or cerebral aqueduct measurements in
      healthy subjects from a wide range of age groups. Such changes should be useful
      for diagnosing diseases that affect the ventricular system and planning surgical
      procedures, especially those involving the ventricular system.

PMID- 24684522
TI  - Avoidance temperament and social-evaluative threat in college students' math
      performance: a mediation model of math and test anxiety.
AB  - BACKGROUND AND OBJECTIVES: Standardized testing has become a common form of
      student evaluation with high stakes, and limited research exists on understanding
      the roles of students' personality traits and social-evaluative threat on their
      academic performance. This study examined the roles of avoidance temperament
      (i.e., fear and behavioral inhibition) and evaluative threat (i.e., fear of
      failure and being viewed as unintelligent) in standardized math test and course
      grades in college students. DESIGN AND METHODS: Undergraduate students (N=184)
      from a large public university were assessed on temperamental fear and behavioral
      inhibition. They were then given 15 minutes to complete a standardized math test.
      After the test, students provided data on evaluative threat and their math
      performance (scores on standardized college entrance exam and average grades in
      college math courses). RESULTS: Results indicate that avoidance temperament was
      linked to social-evaluative threat and low standardized math test scores.
      Furthermore, evaluative threat mediated the influence of avoidance temperament on
      both types of math performance. CONCLUSIONS: Results have educational and
      clinical implications, particularly for students at risk for test anxiety and
      underperformance. Interventions targeting emotion regulation and stress
      management skills may help individuals reduce their math and test anxieties.

PMID- 24684523
TI  - Effects of salinity on antibiotic production in sponge-derived Salinispora
      actinobacteria.
AB  - AIMS: To investigate the effects of growth conditions related to marine habitat
      on antibiotic production in sponge-derived Salinispora actinobacteria. METHODS
      AND RESULTS: Media with varying salt concentration were used to investigate the
      effects of salinity in relation to Salinispora growth and rifamycin production.
      The chemotypic profiles of the model strain Salinispora arenicola M413 was then
      assessed using metabolomic fingerprints from high-pressure liquid chromatography
      with diode array detection (HPLC-DAD) and multivariate data analysis, before
      extending this approach to two other strains of S. arenicola. Fingerprint data
      were generated from extracts of S. arenicola broth cultures grown in media of
      varying salt (NaCl) concentrations. These fingerprints were then compared using
      multivariate analysis methods such as principal components analysis (PCA) and
      orthogonal projection to latent structures discriminant analysis (OPLS-DA). From
      the analysis, a low-sodium growth condition (1% NaCl) was found to delay the
      onset of growth of the model S. arenicola M413 strain when compared to growth in
      media with either 3% artificial sea salt or 3% NaCl. However, low-sodium growth
      conditions also increased cell mass yield and contributed to at least a
      significant twofold increase in rifamycin yield when compared to growth in 3%
      artificial sea salt and 3% NaCl. CONCLUSIONS: The integration of HPLC-DAD and
      multivariate analysis proved to be an effective method of assessing chemotypic
      variations in Salinispora grown in different salt conditions, with clear
      differences between strain-related chemotypes apparent due to varying salt
      concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: The observed variation in
      S. arenicola chemotypic profiles further suggests diversity in secondary
      metabolites in this actinomycete in response to changes in the salinity of its
      environment.

PMID- 24684524
TI  - Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of
      the genotypic and phenotypic disease spectrum.
AB  - Homozygous deletions of chromosome 20p12.3, disrupting the promoter region and
      first three coding exons of the phospholipase C beta1 gene (PLCB1), have
      previously been described in two reports of early infantile epileptic
      encephalopathy (EIEE). Both children were born to consanguineous parents, one
      presented with infantile spasms, the other with migrating partial seizures of
      infancy. We describe an infant presenting with severe intractable epilepsy
      (without a specific EIEE electroclinical syndrome diagnosis) and
      neurodevelopmental delay associated with compound heterozygous mutations in
      PLCB1. A case note review and molecular genetic investigations were performed for
      a child, approximately 10 months of age, admitted to Johns Hopkins University
      Hospital for developmental delay and new-onset seizures. The patient presented at
      6 months of age with developmental delay, followed by the onset of intractable,
      focal, and generalized seizures associated with developmental regression from 10
      months of age. Presently, at 2 years of age, the child has severe motor and
      cognitive delays. Diagnostic microarray revealed a heterozygous 476kb deletion of
      20p12.3 (encompassing PLCB1), which was also detected in the mother. The genomic
      breakpoints for the heterozygous deletion were determined. In order to
      investigate the presence of a second PLCB1 mutation, direct Sanger sequencing of
      the coding region and flanking intronic regions was undertaken, revealing a novel
      heterozygous intron 1 splice site variant (c.99+1G>A) in both the index
      individual and the father. Advances in molecular genetic testing have greatly
      improved diagnostic rates in EIEE, and this report further confirms the important
      role of microarray investigation in this group of disorders. PLCB1-EIEE is now
      reported in a number of different EIEE phenotypes and our report provides further
      evidence for phenotypic pleiotropy encountered in early infantile epilepsy
      syndromes.

PMID- 24684525
TI  - The prevalence and impact of overuse injuries in five Norwegian sports:
      Application of a new surveillance method.
AB  - Little is known about the true extent and severity of overuse injuries in sport,
      largely because of methodological challenges involved in recording them. This
      study assessed the prevalence of overuse injuries among Norwegian athletes from
      five sports using a newly developed method designed specifically for this
      purpose. The Oslo Sports Trauma Research Center Overuse Injury Questionnaire was
      distributed weekly by e-mail to 45 cross-country skiers, 98 cyclists, 50
      floorball players, 55 handball players, and 65 volleyball players for 13 weeks.
      The prevalence of overuse problems at the shoulder, lower back, knee, and
      anterior thigh was monitored throughout the study and summary measures of an
      injury severity score derived from athletes' questionnaire responses were used to
      gauge the relative impact of overuse problems in each area. The area where
      overuse injuries had the greatest impact was the knee in volleyball where, on
      average, 36% of players had some form of complaint (95% CI 32-39%). Other
      prevalent areas included the shoulder in handball (22%, 95% CI 16-27%) the knee
      in cycling (23%, 95% CI 17-28%), and the knee and lower back in floorball (27%,
      95% CI 24-31% and 29%, 95% CI 25-33%, respectively). 

PMID- 24684527
TI  - Ovarian microcystic stromal tumor: report of a new entity with
      immunohistochemical and ultrastructural studies.
AB  - Microcystic stromal tumor is a recently described rare subtype of ovarian tumor
      for which there has been no previously reported ultrastructural study. We report
      a case with the characteristic histological and immunohistochemical features and
      the first ultrastructural study. The immunohistochemical findings of strong and
      diffuse nuclear staining for beta catenin and P27 are suggestive of dysregulation
      of more than one genetic pathway. The ultrastructural findings are supportive of
      the previous postulation of an ovarian stromal origin of the neoplastic cells.

PMID- 24684528
TI  - Recent advances in the pathophysiology and management of eosinophilic
      oesophagitis.
AB  - Eosinophilic oesophagitis is an increasingly recognized allergic gastrointestinal
      disease, which is becoming more common. Although the average age at diagnosis is
      30-50 years, it often affects very young children and carries significant long
      term morbidity. While our understanding of its pathophysiology is accumulating,
      the precise pathways by which the disease arises remain unclear. There are
      inconsistencies in its diagnosis and definition, and a drive towards
      international standardization is underway. Current methods for diagnosis and
      monitoring are relatively invasive, and controversies surround their
      interpretation. Management strategies are imperfect and involve burdensome long
      term dietary exclusions, or drug treatments with uncertain efficacy or serious
      side-effects. It is the focus of a rapidly increasing body of research, the
      latest insights from which are systematically presented in this review. 

PMID- 24684530
TI  - Significant quantum effects in hydrogen activation.
AB  - Dissociation of molecular hydrogen is an important step in a wide variety of
      chemical, biological, and physical processes. Due to the light mass of hydrogen,
      it is recognized that quantum effects are often important to its reactivity.
      However, understanding how quantum effects impact the reactivity of hydrogen is
      still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111)
      alloy that allows the activation of hydrogen and deuterium molecules to be
      examined at individual Pd atom surface sites over a wide range of temperatures.
      Experiments comparing the uptake of hydrogen and deuterium as a function of
      temperature reveal completely different behavior of the two species. The rate of
      hydrogen activation increases at lower sample temperature, whereas deuterium
      activation slows as the temperature is lowered. Density functional theory
      simulations in which quantum nuclear effects are accounted for reveal that
      tunneling through the dissociation barrier is prevalent for H2 up to ~190 K and
      for D2 up to ~140 K. Kinetic Monte Carlo simulations indicate that the effective
      barrier to H2 dissociation is so low that hydrogen uptake on the surface is
      limited merely by thermodynamics, whereas the D2 dissociation process is
      controlled by kinetics. These data illustrate the complexity and inherent quantum
      nature of this ubiquitous and seemingly simple chemical process. Examining these
      effects in other systems with a similar range of approaches may uncover
      temperature regimes where quantum effects can be harnessed, yielding greater
      control of bond-breaking processes at surfaces and uncovering useful chemistries
      such as selective bond activation or isotope separation. 

PMID- 24684531
TI  - Molecular dynamics simulations: insight into molecular phenomena at interfaces.
AB  - Molecular dynamics simulations, when aptly devised, can enhance our fundamental
      understanding of a system, set up a platform for testing theoretical predictions,
      and provide insight and a framework for further experimental studies. This
      feature article highlights the importance of molecular dynamics simulations in
      understanding interfacial phenomena using three case studies involving liquid
      liquid and solid-liquid interfaces. After briefly reviewing molecular dynamics
      methods, we discuss velocity slip at a liquid-liquid interface, the coalescence
      of liquid drops in suspension and in free space, and the behavior of colloidal
      nanoparticles at a liquid-liquid interface. We emphasize the utility of simple
      intermolecular potentials and generic liquids. The case studies exemplify the
      significant insight gained through the molecular modeling approach regarding the
      interfacial phenomena studied. We conclude the highlight with a brief discussion
      illustrating potential shortcomings and pitfalls of molecular dynamics
      simulations. 

PMID- 24684526
TI  - Lung injury and lung cancer caused by cigarette smoke-induced oxidative stress:
      Molecular mechanisms and therapeutic opportunities involving the ceramide
      generating machinery and epidermal growth factor receptor.
AB  - Chronic obstructive pulmonary disease (COPD) and lung cancer are frequently
      caused by tobacco smoking. However, these diseases present opposite phenotypes
      involving redox signaling at the cellular level. While COPD is characterized by
      excessive airway epithelial cell death and lung injury, lung cancer is caused by
      uncontrolled epithelial cell proliferation. Notably, epidemiological studies have
      demonstrated that lung cancer incidence is significantly higher in patients who
      have preexisting emphysema/lung injury. However, the molecular link and common
      cell signaling events underlying lung injury diseases and lung cancer are poorly
      understood. This review focuses on studies of molecular mechanism(s) underlying
      smoking-related lung injury (COPD) and lung cancer. Specifically, the role of the
      ceramide-generating machinery during cigarette smoke-induced oxidative stress
      leading to both apoptosis and proliferation of lung epithelial cells is
      emphasized. Over recent years, it has been established that ceramide is a
      sphingolipid playing a major role in lung epithelia structure/function leading to
      lung injury in chronic pulmonary diseases. However, new and unexpected findings
      draw attention to its potential role in lung development, cell proliferation, and
      tumorigenesis. To address this dichotomy in detail, evidence is presented
      regarding several protein targets, including Src, p38 mitogen-activated protein
      kinase, and neutral sphingomyelinase 2, the major sphingomyelinase that controls
      ceramide generation during oxidative stress. Furthermore, their roles are
      presented not only in apoptosis and lung injury but also in enhancing cell
      proliferation, lung cancer development, and resistance to epidermal growth factor
      receptor-targeted therapy for treating lung cancer.

PMID- 24684533
TI  - Aromatase and regulation of the estrogen-to-androgen ratio in synovial tissue
      inflammation: common pathway in both sexes.
AB  - Sex hormones play an active role in inflammatory responses, with androgens being
      anti-inflammatory, whereas estrogens have both pro- and anti-inflammatory
      effects. In rheumatoid arthritis (RA) patients, low levels of androgens and high
      levels of estrone are found in the synovial fluid. Aromatase is the key enzyme
      for the conversion of androgens into estrogens. Proinflammatory cytokines
      stimulate aromatase activity so that the inflammatory milieu can induce
      conversion of androgens to estrogens. Moreover, testosterone inhibits aromatase
      activity. As local androgen levels are low in RA, this can contribute to high
      aromatase activity in the synovium. Importantly, aromatase-converted estrogens
      are converted into proproliferative and proinflammatory 16-hydroxylated
      estrogens. A hormone involved in aromatase activity is vitamin D, which
      downregulates aromatase in human RA macrophages. Collectively, evidence suggests
      a key role of aromatase in sex hormone balance during chronic inflammation and
      points to the importance of vitamin D as a possible new tool for aromatase
      modulation. 

PMID- 24684532
TI  - Adrenaline stimulates the proliferation and migration of mesenchymal stem cells
      towards the LPS-induced lung injury.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) could modulate inflammation in
      experimental lung injury. On the other hand, adrenergic receptor agonists could
      increase DNA synthesis of stem cells. Therefore, we investigated the therapeutic
      role of adrenaline-stimulated BMSCs on lipopolysaccharide (LPS)-induced lung
      injury. BMSCs were cultured with adrenergic receptor agonists or antagonists.
      Suspensions of lung cells or sliced lung tissue from animals with or without LPS
      induced injury were co-cultured with BMSCs. LPS-stimulated alveolar macrophages
      were co-cultured with BMSCs (with adrenaline stimulation or not) in Transwell for
      6 hrs. A preliminary animal experiment was conducted to validate the findings in
      ex vivo study. We found that adrenaline at 10 MUM enhanced proliferation of BMSCs
      through both alpha- and beta-adrenergic receptors. Adrenaline promoted the
      migration of BMSCs towards LPS-injured lung cells or lung tissue. Adrenaline
      stimulated BMSCs decreased the inflammation of LPS-stimulated macrophages,
      probably through the expression and secretion of several paracrine factors.
      Adrenaline reduced the extent of injury in LPS-injured rats. Our data indicate
      that adrenaline-stimulated BMSCs might contribute to the prevention from acute
      lung injury through the activation of adrenergic receptors, promotion of
      proliferation and migration towards injured lung, and modulation of inflammation.

PMID- 24684534
TI  - Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate
      for reduction of fatigue levels in patients with prostate cancer receiving LHRH
      agonist therapy.
AB  - OBJECTIVES: To investigate whether methylphenidate can alleviate fatigue, as
      measured by the Functional Assessment of Cancer Therapy: Fatigue subscale, in men
      with prostate cancer (PCa) treated with a luteinizing hormone-releasing hormone
      (LHRH) for a minimum of 6 months, and to assess changes in global fatigue and
      quality of life (QoL) as measured by the Bruera Global Fatigue Severity Scale
      (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36),
      respectively. PARTICIPANTS AND METHODS: We performed a single-centre, randomised,
      double-blind, placebo-controlled trial with the aim of recruiting 128
      participants. Men treated with a LHRH agonist for PCa were screened between
      February 2008 and June 2012 for fatigue at our outpatient clinics using the BFS.
      Participants were randomised to receive either 10 mg daily of methylphenidate or
      placebo. Change in fatigue levels and in SF-36 scores between both groups were
      compared using linear regression, adjusted for baseline scores. RESULTS: The
      study was closed prematurely because of poor accrual. Of the 790 subjects
      screened, 24 men were randomised to methylphenidate or placebo (12 per group).
      After 10 weeks, the improvement in mean [sd] fatigue score was greater in the
      methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022).
      The within-group analysis showed a significant improvement in fatigue scores in
      the methylphenidate arm (P = 0.008) but not in the placebo arm (P = 0.82). The
      use of methylphenidate also resulted in a significantly greater improvement in
      QoL as measured by the physical and mental component summary scores than did the
      use of placebo (P = 0.04 for both component scores). CONCLUSIONS: Our findings
      support the beneficial effect of methylphenidate on fatigue and QoL among men
      with LHRH-induced fatigue. Clinicians should be aware of these benefits and
      should consider discussing these findings with patients who have high levels of
      fatigue.

PMID- 24684535
TI  - Observational case series: an algorithm incorporating multidetector computed
      tomography in the medicolegal investigation of human remains after a natural
      disaster.
AB  - An algorithm incorporating multidetector computed tomography (MDCT), digital
      radiographs, and external examination was used to triage cases for noninvasive or
      complete autopsy after a natural disaster. The algorithm was applied to 27
      individuals who died during or soon after the earthquake that struck the Republic
      of Haiti on January 12, 2010. Of the 27 cases reviewed, 7 (26%) required a
      complete autopsy to determine cause and manner of death. In the remaining 20
      (74%), cause and manner of death were determined with a reasonable degree of
      medical certainty after review of circumstances, an external examination, and
      postmortem imaging by MDCT and digital radiography (noninvasive autopsy). MDCT
      was particularly useful in detecting skeletal fractures caused by blunt force
      injury which were not evident on digital radiographs. The algorithm incorporating
      postmortem MDCT can be useful in the triage of human remains for autopsy after a
      natural disaster. 

PMID- 24684536
TI  - Design of starch-graft-PEI polymers: an effective and biodegradable gene delivery
      platform.
AB  - Starch and starch derivatives are widely utilized pharmaceutical excipients. The
      concept of this study was to make use of starch as a biodegradable backbone and
      to modify it with low-toxic, but poor transfecting low molecular weight
      polyethylenimine (PEI) in order to achieve better transfection efficacy while
      maintaining enzymatic degradability. A sufficiently controllable conjugation
      could be achieved via a water-soluble intermediate of oxidized starch and an
      optimized reaction protocol. Systematic variation of MW fraction of the starch
      backbone and the amount of cationic side chains (0.8 kDa bPEI) yielded a series
      of starch-graft-PEI copolymers. Following purification and chemical
      characterization, nanoscale complexes with plasmid DNA were generated and studied
      regarding cytotoxicity and transfection efficacy. The optimal starch-graft-PEI
      polymers consisted of >100 kDa MW starch and contained 30% (wt) of PEI, showing
      similar transfection levels as 25 kDa bPEI, and being less cytotoxic and
      enzymatically biodegradable. 

PMID- 24684537
TI  - ES&T's best papers of 2013: under pressure.

PMID- 24684538
TI  - 96-well microtiter plates for biofouling simulation in biomedical settings.
AB  - Microtiter plates with 96 wells are routinely used in biofilm research mainly
      because they enable high-throughput assays. These platforms are used in a variety
      of conditions ranging from static to dynamic operation using different shaking
      frequencies and orbital diameters. The main goals of this work were to assess the
      influence of nutrient concentration and flow conditions on biofilm formation by
      Escherichia coli in microtiter plates and to define the operational conditions to
      be used in order to simulate relevant biomedical scenarios. Assays were performed
      in static mode and in incubators with distinct orbital diameters using different
      concentrations of glucose, peptone and yeast extract. Computational fluid
      dynamics (CFD) was used to simulate the flow inside the wells for shaking
      frequencies ranging from 50 to 200 rpm and orbital diameters from 25 to 100 mm.
      Higher glucose concentrations enhanced adhesion of E. coli in the first 24 h, but
      variation in peptone and yeast extract concentration had no significant impact on
      biofilm formation. Numerical simulations indicate that 96-well microtiter plates
      can be used to simulate a variety of biomedical scenarios if the operating
      conditions are carefully set.

PMID- 24684539
TI  - Competition between monomeric and dimeric crystals in schematic models for
      globular proteins.
AB  - Advances in experimental techniques and in theoretical models have improved our
      understanding of protein crystallization. However, they have also left open
      questions regarding the protein phase behavior and self-assembly kinetics, such
      as why (nearly) identical crystallization conditions can sometimes result in the
      formation of different crystal forms. Here, we develop a patchy particle model
      with competing sets of patches that provides a microscopic explanation of this
      phenomenon. We identify different regimes in which one or two crystal forms can
      coexist with a low-density fluid. Using analytical approximations, we extend our
      findings to different crystal phases, providing a general framework for treating
      protein crystallization when multiple crystal forms compete. Our results also
      suggest different experimental routes for targeting a specific crystal form, and
      for reducing the dynamical competition between the two forms, thus facilitating
      protein crystal assembly. 

PMID- 24684540
TI  - Distribution of branches in whole starches from maize mutants deficient in starch
      synthase III.
AB  - An earlier study explored the possibility of analyzing the distribution of
      branches directly in native, whole starch without isolating the amylopectin
      component. The aim of this study was to explore if this approach can be extended
      to include starch mutants. Whole starches from du1 maize mutants deficient in
      starch synthase III (SSIII) with amylose content of ~30-40% were characterized
      and compared with the wild type of the common genetic background W64A. Clusters
      were produced from whole starch by hydrolysis with alpha-amylase of Bacillus
      amyloliquefaciens. Their compositions of building blocks and chains were analyzed
      further by complete alpha-amylolysis and by debranching, respectively, whereafter
      the products were subjected to gel permeation and anion exchange chromatography.
      The size and structure of the clusters were compared with those of their isolated
      amylopectin component. Whereas the whole starch of the wild type sample had a
      branched structure similar to that of its amylopectin component, the results
      showed that the du1 mutation resulted in more singly branched building blocks in
      the whole starch compared to the isolated amylopectin. This suggested that
      amylose and/or intermediate materials in whole du1 starches likely contributed to
      the composition of branches. This study explored an alternative procedure to
      characterize the composition of branches in the whole starch without
      fractionating the components. 

PMID- 24684541
TI  - High functional CD70 expression on alpha-type 1-polarized dendritic cells from
      patients with chronic lymphocytic leukaemia.
AB  - Antigen-loaded dendritic cells (DCs) used as anticancer vaccine holds promise for
      therapy, but needs to be optimized. The most frequently described DC vaccine is
      being matured with a cocktail containing prostaglandin E2 (PGE2 DC). However,
      even though PGE2 DCs express both costimulatory and migratory receptors, their IL
      12p70-prodcution is low, leading to an insufficient Th1 immune response. As an
      alternative, alpha-type-1 polarized DCs (alphaDC1s) have shown a superior
      production of IL-12p70 and subsequent activation of effector cells. From chronic
      lymphocytic leukaemia (CLL) patients, alphaDC1s can be generated to induce a
      functional Th1-immune response. Yet, another costimulatory receptor, CD70,
      appears to be essential for optimal DC function by promotion of T cell survival
      and function. So far, PGE2 is suggested as one of the most important factors for
      the induction of CD70 expression on DCs. Therefore, we wanted to investigate
      whether alphaDC1s have the ability to express functional CD70. We found that CD70
      expression on alphaDC1s could be upregulated in the same manner as PGE2 DCs. In
      an allogeneic mixed leucocyte reaction, we found that antibody-blocking of CD70
      on alphaDC1s from controls reduced effector cell proliferation although this
      could not be found when using CLL alphaDC1s. Nevertheless, CD70-blocking of
      alphaDC1s from both controls and patients with CLL had a negative influence on
      the production of both IL-12p70 and the Th1 cytokine IFN-gamma, while the
      production of the Th2 cytokine IL-5 was enhanced. Together, this study further
      suggests that alphaDC1s should be considered as a suitable candidate for clinical
      antitumour vaccine strategies in patients with CLL.

PMID- 24684542
TI  - Assessment of messenger RNA (mRNA) of Mycobacterium tuberculosis as a marker of
      cure in patients with pulmonary tuberculosis.
AB  - AIMS: To analyse the performance of RT-qPCR using 85B mRNA in the diagnosis of
      Mycobacterium tuberculosis infection and in the assessment of the response to
      treatment for pulmonary tuberculosis (TB). METHODS AND RESULTS: Ninety-eight
      patients with signs of pulmonary TB were selected: 56 were considered infected
      with Myco. tuberculosis and they had positive cultures or evident clinical
      response to anti-TB treatment. Patients with pulmonary tuberculosis were
      evaluated by culture and RT-qPCR for a 30-day specific treatment. It was found
      that both tests demonstrated a decline in viable bacilli at 15 and 30 days after
      the beginning of the therapy in most of the patients. The quantification of the
      85B mRNA target was performed in 52 patients who had initially shown positive
      results by RT-qPCR and who were followed on the days 15 and 30 after the specific
      treatment. Thus 85B mRNA was detectable in sputum samples in 52 patients with a
      confirmed diagnosis of pulmonary tuberculosis on day 0. During the specific
      treatment the 85B mRNA was detectable in 13 patients on day 15 and in only three
      patients on day 30. CONCLUSIONS: Mycobacterium tuberculosis mRNA in the sputum is
      a useful prognostic marker and its quantification, an early and reliable
      indicator for monitoring response to treatment, drug resistance, re-infection and
      relapse. SIGNIFICANCE AND IMPACT OF THE STUDY: RT-qPCR is a tool that can be used
      in clinical and therapeutic monitoring as an indicator of bacterial resistance
      and indicator of the period of transmissibility of Myco. tuberculosis in patients
      with pulmonary TB undergoing treatment.

PMID- 24684543
TI  - Maternal mind-mindedness during infancy, general parenting sensitivity and
      observed child feeding behavior: a longitudinal study.
AB  - Maternal mind-mindedness, or the tendency to view the child as a mental agent,
      has been shown to predict sensitive and responsive parenting behavior. As yet the
      role of mind-mindedness has not been explored in the context of feeding
      interactions. This study evaluates the relations between maternal mind-mindedness
      at 6 months of infant age and subsequently observed maternal sensitivity and
      feeding behaviors with children at age 1 year. Maternal mind-mindedness was
      greater in mothers who had breast-fed compared to formula-fed. Controlling for
      breast-feeding, mind-mindedness at 6 months was correlated with observations of
      more sensitive and positive feeding behaviors at 1 year of age. Mind-mindedness
      was also associated with greater general maternal sensitivity in play and this
      general parenting sensitivity mediated the effect of mind-mindedness on more
      sensitive and positive feeding behaviors. Interventions to promote maternal
      tendency to consider their child's mental states may encourage more adaptive
      parental feeding behaviors.

PMID- 24684544
TI  - Genetic basis of cranial cruciate ligament rupture (CCLR) in dogs.
AB  - Cranial Cruciate Ligament rupture (CCLR) is one of the most common forms of
      lameness in dogs and is analogous to rupture of the anterior cruciate ligament in
      humans, for which it can serve as a model. As there is a strong breed-related
      predisposition to CCLR in dogs, a study was undertaken to consider putative
      genetic components in susceptible dog breeds. A candidate gene, single nucleotide
      polymorphism (SNP) genotyping approach using MALDI-TOF mass spectrometry
      (Sequenom Ltd) was designed to investigate several CCLR-susceptible dog breeds
      and identify CCLR-associated genes/gene regions that may confer susceptibility or
      resistance. A meta-analysis was performed using the breed case/control candidate
      gene data to identify SNP associations that were common to the whole cohort of
      susceptible dogs. We identified SNPs in key genes involved in ligament strength,
      stability and extracellular matrix formation (COL5A1, COL5A2, COL1A1, COL3A1,
      COL11A1, COL24A1, FBN1, LOX, LTBP2) which were significantly associated with CCLR
      susceptibility across the dog breeds used in this study. These SNPs could have an
      involvement in CCLR due to a detrimental effect on ligament structure and
      strength. This is the first published candidate gene study that has revealed
      significant genetic associations with canine CCLR.

PMID- 24684545
TI  - Direct approaches to nitriles via highly efficient nitrogenation strategy through
      C-H or C-C bond cleavage.
AB  - Because of the importance of nitrogen-containing compounds in chemistry and
      biology, organic chemists have long focused on the development of novel
      methodologies for their synthesis. For example, nitrogen-containing compounds
      show up within functional materials, as top-selling drugs, and as bioactive
      molecules. To synthesize these compounds in a green and sustainable way,
      researchers have focused on the direct functionalization of hydrocarbons via C-H
      or C-C bond cleavage. Although researchers have made significant progress in the
      direct functionalization of simple hydrocarbons, direct C-N bond formation via C
      H or C-C bond cleavage remains challenging, in part because of the unstable
      character of some N-nucleophiles under oxidative conditions. The nitriles are
      versatile building blocks and precursors in organic synthesis. Recently, chemists
      have achieved the direct C-H cyanation with toxic cyanide salts in the presence
      of stoichiometric metal oxidants. In this Account, we describe recent progress
      made by our group in nitrile synthesis. C-H or C-C bond cleavage is a key process
      in our strategy, and azides or DMF serve as the nitrogen source. In these
      reactions, we successfully realized direct nitrile synthesis using a variety of
      hydrocarbon groups as nitrile precursors, including methyl, alkenyl, and alkynyl
      groups. We could carry out C(sp(3))-H functionalization on benzylic, allylic, and
      propargylic C-H bonds to produce diverse valuable synthetic nitriles. Mild
      oxidation of C?C double-bonds and C=C triple-bonds also produced nitriles. The
      incorporation of nitrogen within the carbon skeleton typically involved the
      participation of azide reagents. Although some mechanistic details remain
      unclear, studies of these nitrogenation reactions implicate the involvement of a
      cation or radical intermediate, and an oxidative rearrangement of azide
      intermediate produced the nitrile. We also explored environmentally friendly
      oxidants, such as molecular oxygen, to make our synthetic strategy more
      attractive. Our direct nitrile synthesis methodologies have potential
      applications in the synthesis of biologically active molecules and drug
      candidates.

PMID- 24684546
TI  - Hypertriglyceridemia and low high-density lipoprotein cholesterolemia are
      associated with increased hazard for urolithiasis.
AB  - PURPOSE: To assess the association between dyslipidemia and urolithiasis, a
      propensity score-matching study was performed. PATIENTS AND METHODS: Fasting
      blood samples were taken, and serum lipid profiles were measured in 655 stone
      formers (SF) and 1965 propensity score-matched controls between 2005 and 2011.
      The controls, from a health-screening program, did not have a history of
      dyslipidemia or statin use and have any evidence of stone disease, as determined
      by abdominal radiography, ultrasonography examination. Propensity score-matching
      with respect to age, sex, and body mass index was used to minimize selection
      bias, and the logistic regression analysis was adjusted for other components of
      metabolic syndrome. RESULTS: Compared with controls, the SF group had
      significantly higher mean triglyceride and lower total cholesterol, low-density
      lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol
      levels (each P<0.001). The SF group was also more likely to have
      hypertriglyceridemia and low HDL-cholesterolemia, and less likely to have
      hypercholesterolemia and high LDL cholesterolemia compared with controls (each
      P<0.05). When adjusted for other components of metabolic syndrome including
      obesity, presence of diabetes mellitus or hypertension, the odds ratio (OR) for
      urinary stones appeared with hypercholesterolemia (OR=0.747, P=0.003),
      hypertriglyceridemia (OR=1.901, P<0.001), low HDL cholesterolemia (OR=1.886,
      P<0.001) and high LDL cholesterolemia (OR=0.610, P<0.001). CONCLUSIONS: Our study
      implies that dyslipidemia may play a crucial part in urinary stone risk.

PMID- 24684547
TI  - Safety and efficacy of a novel injectable filler in the treatment of nasolabial
      folds: polymethylmethacrylate and cross-linked dextran in hydroxypropyl
      methylcellulose.
AB  - Nasolabial folds are a sign of aging and increasing number of people want filler
      injections in their nasolabial folds to look younger. Various dermal fillers are
      used for the correction of nasolabial folds. Recently, a novel injectible filler,
      polymethylmethacrylate (PMMA) and cross-linked dextran in hydroxypropyl
      methylcellulose, was introduced for facial contouring. This study was designed as
      a six-month, prospective, single-blinded, and open-label study in two centers
      located in Korea. Nineteen Korean patients received the novel filler injections
      on both nasolabial folds. At Weeks 4, 12, and 24, the efficacy and safety of the
      dermal filler were evaluated by blinded-investigators using clinical photographs.
      The mean Wrinkle Severity Rating Scale revealed significant decrease after dermal
      filler injections at each study visit. The decreased Wrinkle Severity Rating
      Scale was maintained for 6 months (p < 0.0001). The Global Aesthetic Improvement
      score showed an improvement greater than 2 in 95% of the per-proto col population
      24 weeks after the injections. All patients (100%) experienced an improvement of
      their nasolabial folds at Week 24. There were no complications related to the
      novel filler injection. The novel dermal filler, PMMA, and cross-linked dextran
      in hydroxylpropyl methylcellulose, can be another safe and effective treatment
      option in the treatment of nasolabial folds.

PMID- 24684548
TI  - Hepatocyte necroptosis induced by ischemic acute kidney injury in rats.
AB  - While ischemic acute kidney injury (IAKI) is known often to cause hepatic injury,
      little is known about necroptosis involved in the hepatic injury. The purposes of
      this study were to identify necroptosis involvement and observe morphological
      changes of hepatocytes in hepatic injury induced by IAKI in rats. Based on
      successfully established IAKI rat models, enzyme-linked immunosorbent assay
      illustrated a significant higher level of tumor necrosis factor a in serums of
      IAKI animals. Tumor necrosis factor receptor a (TNFRa) and receptor interacting
      protein kinase 3 (RIPk3) showed significant higher expressions in immunoblot
      analyses and positive hepatocytes of RIPk3 immunohistochemical staining were also
      evident in livers of IAKI rats. In addition, light microscopy revealed necrotic
      lesions that contain hepatocytes ongoing necroptosis besides necrotic cells in
      IAKI livers. Electron microscopy revealed at least three types of necrotic
      hepatocytes, they were edema necrosis, vacuolization necrosis, and necroptosis.
      Hepatocytes undergoing necroptosis had both necrosis and apoptosis morphological
      characteristics, they were necrosis cytoplasm and apoptosis-like nucleus. Among
      cellular organelles of hepatocyte with necrosis, membranous structures, such as
      cell membrane, endoplasmic reticular system, and mitochondria were more
      vulnerable to the stress of IAKI and deformed nucleuses varied in shape and lytic
      or pyknotic chromatin appearances were noted under insults of IAKI. In
      conclusion, hepatocyte undergoing necroptosis, RIPk3-mediated necroptosis partly
      contributes to hepatic necrosis induced by IAKI. Both membranous structures and
      nucleuses of hepatocyte were vulnerable to ischemic acute kidney injury.

PMID- 24684549
TI  - Resonant plasmonic enhancement of single-molecule fluorescence by individual gold
      nanorods.
AB  - Enhancing the fluorescence of a weak emitter is important to further extend the
      reach of single-molecule fluorescence imaging to many unexplored systems. Here we
      study fluorescence enhancement by isolated gold nanorods and explore the role of
      the surface plasmon resonance (SPR) on the observed enhancements. Gold nanorods
      can be cheaply synthesized in large volumes, yet we find similar fluorescence
      enhancements as literature reports on lithographically fabricated nanoparticle
      assemblies. The fluorescence of a weak emitter, crystal violet, can be enhanced
      more than 1000-fold by a single nanorod with its SPR at 629 nm excited at 633 nm.
      This strong enhancement results from both an excitation rate enhancement of ~130
      and an effective emission enhancement of ~9. The fluorescence enhancement,
      however, decreases sharply when the SPR wavelength moves away from the excitation
      laser wavelength or when the SPR has only a partial overlap with the emission
      spectrum of the fluorophore. The reported measurements of fluorescence
      enhancement by 11 nanorods with varying SPR wavelengths are consistent with
      numerical simulations. 

PMID- 24684550
TI  - Grass pollen allergens globally: the contribution of subtropical grasses to
      burden of allergic respiratory diseases.
AB  - Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies
      of grasses are major aeroallergen sources worldwide. The subtropical
      Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g.
      Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India,
      Asia, Australia and the Americas, where a large and increasing proportion of the
      world's population abide. These grasses are phylogenetically and ecologically
      distinct from temperate grasses. With the advent of global warming, it is
      conceivable that the geographic distribution of subtropical grasses and the
      contribution of their pollen to the burden of allergic rhinitis and asthma will
      increase. This review aims to provide a comprehensive synthesis of the current
      global knowledge of (i) regional variation in allergic sensitivity to subtropical
      grass pollens, (ii) molecular allergenic components of subtropical grass pollens
      and (iii) allergic responses to subtropical grass pollen allergens in relevant
      populations. Patients from subtropical regions of the world show higher allergic
      sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to
      temperate grass pollens. The group 1 allergens are amongst the allergen
      components of subtropical grass pollens, but the group 5 allergens, by which
      temperate grass pollen extracts are standardized for allergen content, appear to
      be absent from both subfamilies of subtropical grasses. Whilst there are shared
      allergenic components and antigenic determinants, there are additional clinically
      relevant subfamily-specific differences, at T- and B-cell levels, between pollen
      allergens of subtropical and temperate grasses. Differential immune recognition
      of subtropical grass pollens is likely to impact upon the efficacy of allergen
      immunotherapy of patients who are primarily sensitized to subtropical grass
      pollens. The literature reviewed herein highlights the clinical need to
      standardize allergen preparations for both types of subtropical grass pollens to
      achieve optimal diagnosis and treatment of patients with allergic respiratory
      disease in subtropical regions of the world. 

PMID- 24684553
TI  - Bottom-up assembly of hydrophobic nanocrystals and graphene nanosheets into
      mesoporous nanocomposites.
AB  - A general strategy for constructing graphene-based nanocomposites is achieved by
      emulsion-based bottom-up self-assembly of hydrophobic nanocrystals (NCs) to
      positively charged colloidal spheres, followed by the electrostatic assembly of
      NC colloidal spheres with negatively charged graphene oxide in an acidulous
      aqueous solution. With a simple heat treatment, 3D mesoporous NC spheres/graphene
      composites are obtained. TiO2/graphene composites typically exhibit a better rate
      capability and cycle performance than do the corresponding isolated TiO2 spheres.

PMID- 24684551
TI  - Modes of physiologic H2S signaling in the brain and peripheral tissues.
AB  - SIGNIFICANCE: Hydrogen sulfide (H2S), once associated with rotten eggs and
      sewers, is now recognized as a gasotransmitter that is synthesized in vivo in a
      regulated fashion. This ancient gaseous molecule has been retained throughout
      evolution to perform various roles in different life forms. H2S modulates
      important signaling functions in diverse cellular processes ranging from
      regulation of blood pressure to redox homeostasis. RECENT ADVANCES: One of the
      modes by which H2S signals is by post-translational modification of reactive
      cysteine residues in a process designated as sulfhydration, resulting in
      conversion of the -SH groups of target cysteine residues to -SSH. Using the
      modified biotin-switch assay and a fluorescent maleimide-based analysis,
      sulfhydration of several proteins has been detected in various cell types.
      Aberrant sulfhydration patterns occur in neurodegenerative conditions such as
      Parkinson's disease. CRITICAL ISSUES: The exact concentration, source of H2S, and
      conditions under which various stores of H2S are utilized have not been fully
      elucidated. Currently, available inhibitors of the biosynthetic enzymes of H2S
      lack sufficient specificity to shed light on detailed mechanisms of H2S action.
      Probes with a higher sensitivity that can reliably detect cellular and tissue H2S
      levels are yet to be developed. FUTURE DIRECTIONS: Availability of advanced
      probes and biosynthesis inhibitors would help in the measurement of real-time
      changes of endogenous H2S levels in an in vivo context. The study of the dynamics
      of sulfhydration and nitrosylation of critical cysteine residues of regulatory
      proteins involved in physiology and pathophysiology is an area of interest for
      the future.

PMID- 24684552
TI  - Renal transplantation using belatacept without maintenance steroids or
      calcineurin inhibitors.
AB  - Kidney transplantation remains limited by toxicities of calcineurin inhibitors
      (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing
      regimens rely on steroids and have higher rejection rates. Experimentally, donor
      bone marrow and sirolimus promote belatacept's efficacy. To investigate a
      belatacept-based regimen without CNIs or steroids, we transplanted recipients of
      live donor kidneys using alemtuzumab induction, monthly belatacept and daily
      sirolimus. Patients were randomized 1:1 to receive unfractionated donor bone
      marrow. After 1 year, patients were allowed to wean from sirolimus. Patients were
      followed clinically and with surveillance biopsies. Twenty patients were
      transplanted, all successfully. Mean creatinine (estimated GFR) was 1.10 +/- 0.07
      mg/dL (89 +/- 3.56 mL/min) and 1.13 +/- 0.07 mg/dL (and 88 +/- 3.48 mL/min) at 12
      and 36 months, respectively. Excellent results were achieved irrespective of bone
      marrow infusion. Ten patients elected oral immunosuppressant weaning, seven of
      whom were maintained rejection-free on monotherapy belatacept. Those failing to
      wean were successfully maintained on belatacept-based regimens supplemented by
      oral immunosuppression. Seven patients declined immunosuppressant weaning and
      three patients were denied weaning for associated medical conditions; all
      remained rejection-free. Belatacept and sirolimus effectively prevent kidney
      allograft rejection without CNIs or steroids when used following alemtuzumab
      induction. Selected, immunologically low-risk patients can be maintained solely
      on once monthly intravenous belatacept.

PMID- 24684554
TI  - Total synthesis of (+/-)-cafestol: a late-stage construction of the furan ring
      inspired by a biosynthesis strategy.
AB  - An efficient bioinspired approach to the total synthesis of (+/-)-cafestol
      features a late-stage installation of the furan ring with a mild Au-catalyzed
      cycloisomerization. The Et2AlCl-promoted aldehyde-ene cyclization and subsequent
      Friedel-Crafts reaction deliver a requisite tricyclic system in gram scale with
      high stereo- and regioselectivity. Moreover, a highly stereoselective SmI2
      mediated aldehyde-alkene radical cyclization furnishes the key
      bicyclo[3.2.1]octane skeleton to offer an advanced intermediate for the synthesis
      of other oxygenated ent-kaurene diterpenoids. 

PMID- 24684555
TI  - Effective maybe, but is it cost-effective?

PMID- 24684556
TI  - Have infant gross motor abilities changed in 20 years? A re-evaluation of the
      Alberta Infant Motor Scale normative values.
AB  - AIM: To compare the original normative data of the Alberta Infant Motor Scale
      (AIMS) (n=2202) collected 20 years ago with a contemporary sample of Canadian
      infants. METHOD: This was a cross-sectional cohort study of 650 Canadian infants
      (338 males, 312 females; mean age 30.9 wks [SD 15.5], range 2 wks-18 mo) assessed
      once on the AIMS. Assessments were stratified by age, and infants proportionally
      represented the ethnic diversity of Canada. Logistic regression was used to place
      AIMS items on an age scale representing the age at which 50% of the infants
      passed an item on the contemporary data set and the original data set. Forty
      three items met the criterion for stable regression results in both data sets.
      RESULTS: The correlation coefficient between the age locations of items on the
      original and contemporary data sets was 0.99. The mean age difference between
      item locations was 0.7 weeks. Age values from the original data set when
      converted to the contemporary scale differed by less than 1 week. INTERPRETATION:
      The sequence and age at emergence of AIMS items has remained similar over 20
      years and current normative values remain valid. Concern that the 'back to sleep'
      campaign has influenced the age at emergence of gross motor abilities is not
      supported.

PMID- 24684557
TI  - Do insulation products of man-made vitreous fibres still cause skin discomfort?
AB  - BACKGROUND: Man-made vitreous fibres (MMVFs) are used in products for insulation
      and as reinforcement in materials. Contamination of the skin may arise through
      direct or indirect contact, and from the deposition of airborne fibres. The
      scientific basis regarding the effects on skin of MMVFs dates from 1970-1980.
      OBJECTIVES: To investigate whether currently used insulation MMVF products still
      cause skin discomfort. METHODS: Focus group interviews and structured interviews
      were performed among workers engaged in insulation tasks and among do-it-yourself
      consumers with a recent experience of MMVF products. RESULTS: A majority of
      interviewees experienced skin discomfort when handling MMVF products. Complaints
      caused by traditional (yellow) glass fibre products were more severe than those
      caused by products of rock or slag wool fibres. The wrists, forearms, neck and
      face were the locations where the skin was most affected. The situations causing
      problems varied between occupational tasks, but working with the hands over the
      head or in narrow spaces were described as the worst situations. Building
      construction apprentices performed insulation tasks more often than senior
      workers. CONCLUSIONS: MMVF insulation products do still cause skin discomfort.
      Updated knowledge about people's experiences of work with such products should
      influence legislation.

PMID- 24684558
TI  - Injectable biocompatible and biodegradable pH-responsive hollow particle gels
      containing poly(acrylic acid): the effect of copolymer composition on gel
      properties.
AB  - The potential of various pH-responsive alkyl (meth)acrylate ester- and
      (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co
      acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA),
      to form pH-sensitive biocompatible and biodegradable hollow particle gel
      scaffolds for use in non-load-bearing soft tissue regeneration have been
      explored. The optimal copolymer design criteria for preparation of these
      materials have been established. Physical gels which are both pH- and redox
      sensitive were formed only from PMMA-AA copolymers. MMA is the optimal
      hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g.,
      MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels
      were prepared at physiological pH range from concentrated dispersions of swollen,
      hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'
      dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle
      swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels
      with lower AA contents feature lower swelling ratios, mechanical strengths, and
      ductilities. Increasing the swelling ratio (e.g., through increasing AA content)
      decreased the intraparticle elasticity; however, intershell contact and gel
      elasticity were found to increase. The mechanical properties and performance of
      the gels were tuneable upon varying the copolymers' compositions and the
      structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were
      more elastic and ductile. The biodegradability and cytotoxicity of the new hollow
      particle gels were tested for the first time and related to their composition,
      mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels
      have shown good biocompatibility, biodegradability, strength, and interconnected
      porosity and therefore have good potential as a tissue repair agent. 

PMID- 24684559
TI  - Assessing young children's intention-reading in authentic communicative contexts:
      preliminary evidence and clinical utility.
AB  - BACKGROUND: Identifying what a communication partner is looking at (referential
      intention) and why (social intention) is essential to successful social
      communication, and may be challenging for children with social communication
      deficits. This study explores a clinical task that assesses these intention
      reading abilities within an authentic context. AIMS: To gather evidence of the
      task's reliability and validity, and to discuss its clinical utility. METHODS &
      PROCEDURES: The intention-reading task was administered to twenty 4-7-year-olds
      with typical development (TD) and ten with autism spectrum disorder (ASD). Task
      items were embedded in an authentic activity, and they targeted the child's
      ability to identify the examiner's referential and social intentions, which were
      communicated through joint attention behaviours. Reliability and construct
      validity evidence were addressed using established psychometric methods. OUTCOMES
      & RESULTS: Reliability and validity evidence supported the use of task scores for
      identifying children whose intention-reading warranted concern. Evidence
      supported the reliability of task administration and coding, and item-level codes
      were highly consistent with overall task performance. Supporting task validity,
      group differences aligned with predictions, with children with ASD exhibiting
      poorer and more variable task scores than children with TD. Also, as predicted,
      task scores correlated significantly with verbal mental age and ratings of
      parental concerns regarding social communication abilities. CONCLUSIONS &
      IMPLICATIONS: The evidence provides preliminary support for the reliability and
      validity of the clinical task's scores in assessing young children's real-time
      intention-reading abilities, which are essential for successful interactions in
      school and beyond.

PMID- 24684560
TI  - Melanoma never says die.
AB  - Drug resistance in melanoma is commonly attributed to ineffective apoptotic
      pathways. Targeting apoptosis regulators is thus considered a promising approach
      to sensitizing melanoma to therapy. In the previous issue of Experimental
      Dermatology, Plotz and Eberle discuss the role that apoptosis plays in melanoma
      progression and drug resistance and the utility of apoptosis-inducing BH3
      mimetics as targeted therapy. There are a number of compounds in clinical
      development and the field seems close to translating recent findings into
      benefits for patients with melanoma. Thus, this viewpoint is timely and achieves
      a valuable summary of the current state of apoptosis-inducing therapy of
      melanoma.

PMID- 24684561
TI  - Ligation of the left hepatic vein for dilated intrahepatic collaterals late after
      fontan operation.
AB  - A 17-year-old male presented with two episodes of syncope, cyanosis, and exercise
      intolerance 13 years after the Fontan operation. Echocardiography and magnetic
      resonance imaging showed dilated intrahepatic collaterals, which drained into the
      atrium through the left hepatic vein, and 24-hour Holter monitoring revealed
      sinus node dysfunction. We performed ligation of the left hepatic vein using
      intrahepatic collaterals as channels draining hepatic venous blood into the
      Fontan pathway, and implanted an epicardial dual chamber pacemaker. At one-year
      follow-up, the patient remained asymptomatic and his cardiac performance was much
      improved.

PMID- 24684563
TI  - Crystal structure and magnetic properties of FeSeO(3)F--alternating
      antiferromagnetic S = 5/2 chains.
AB  - The new oxofluoride FeSeO3F, which is isostructural with FeTeO3F and GaTeO3F, was
      prepared by hydrothermal synthesis, and its structure was determined by X-ray
      diffraction. The magnetic properties of FeSeO3F were characterized by magnetic
      susceptibility and specific heat measurements, by evaluating its spin exchanges
      on the basis of density functional theory (DFT) calculations, and by performing a
      quantum Monte Carlo simulation of the magnetic susceptibility. FeSeO3F
      crystallizes in the monoclinic space group P21/n and has one unique Se(4+) ion
      and one unique Fe(3+) ion. The building blocks of FeSeO3F are [SeO3] trigonal
      pyramids and cis-[FeO4F2] distorted octahedra. The cis-[FeO4F2] octahedra are
      condensed by sharing the O-O and F-F edges alternatingly to form [FeO3F]infinity
      chains, which are interconnected via the [SeO3] pyramids by corner-sharing. The
      magnetic susceptibility of FeSeO3F is characterized by a broad maximum at 75(2) K
      and a long-range antiferromagnetic order below ~45 K. The latter is observed by
      magnetic susceptibility and specific heat measurements. DFT calculations show
      that the Fe-F-Fe spin exchange is stronger than the Fe-O-Fe exchange, so each
      [FeO3F]infinity chain is a Heisenberg antiferromagnetic chain with alternating
      antiferromagnetic spin exchanges. The temperature dependence of the magnetic
      susceptibility is well-reproduced by a quantum-Monte Carlo simulation. 

PMID- 24684562
TI  - Acute aortic dissection diagnosed after embalming: macroscopic and microscopic
      findings.
AB  - A 58-year-old man died suddenly in Madagascar and poisoning was suspected. The
      body was embalmed after death and the general state of preservation was good. We
      found a major aortic dissection with a large false lumen from the aortic root to
      the common iliac arteries and a hemopericardium with formalinized blood clot. The
      intimal tear was on the ascending aorta, and an intramural hemorrhage was noted
      at the right coronary artery, attesting to a retrograde dissection. Microscopic
      studies confirmed aortic dissection with extensive intramural hemorrhage and also
      confirmed the retrograde dissection to the right coronary artery with a reduction
      of 90% of the true lumen. Classically, aortic dissection occurs in individuals
      with hypertension and individuals with genetic disorders of collagen formation.
      The diagnosis is often first established at the postmortem examination. Aortic
      dissection is therefore dealt with largely in necropsy studies. The usual cause
      of death is rupture into the pericardial sac. One case of bloodless dissection
      has been reported but the sudden death was explained by acute myocardial ischemia
      secondary to dissection of the left coronary artery. In our case, we found major
      hemopericardium and also intramural hemorrhage at the right coronary artery. We
      were able to make the diagnosis of aortic dissection and exclude the suspicion of
      homicide 15 days after death and after embalming. 

PMID- 24684564
TI  - In vitro evaluation of adherence of Candida albicans, Candida glabrata, and
      Streptococcus mutans to an acrylic resin modified by experimental coatings.
AB  - This study evaluated the effect of experimental coatings, containing zwitterion
      or hydrophilic monomers, on the adherence of Candida albicans, Candida glabrata,
      and Streptococcus mutans to an acrylic resin. Acrylic samples (smooth or rough
      surfaces) were left untreated (control) or coated with one of the following
      experimental coatings: 3-hydroxypropylmethacrylate (HP) or sulfobetaine
      methacrylate (S), at concentrations of 25, 30, or 35%. Half of the specimens were
      coated with saliva. The adhesion test was performed by incubating specimens in C.
      albicans, C. glabrata, and S. mutans suspensions at 37 degrees C for 90 min. The
      number of adhered microorganisms was determined by metabolic activity (XTT) and
      by cell viability (CFU). All coated specimens exhibited lower absorbance and CFU
      values compared to control specimens. Saliva and roughness did not promote
      microorganism adherence. An XPS analysis confirmed the modification in the
      chemical composition of the coatings in the experimental samples. These
      experimental coatings significantly reduced the adherence of C. albicans, C.
      glabrata and S. mutans to acrylic resin.

PMID- 24684565
TI  - Insecticide residues in head lettuce, cabbage, Chinese cabbage, and broccoli
      grown in fields.
AB  - The residues of four insecticides belonging to different families were studied on
      head lettuce (Lactuca sativa L. var. capitata L.), cabbage (Brassica oleracea
      Linn. var. capitata DC.), Chinese cabbage (Brassica pekinensis Skeels), and
      broccoli (Brassica oleracea var. italica) after pesticide application. To reduce
      application variability, a tank mix of acetamiprid 20% SP, chlorpyrifos 22.5% EC,
      deltamethrin 2.4% SC, and methomyl 40% SP was applied at recommended and double
      doses. Initial deposits of all pesticides on head lettuce were higher than those
      of the other three crops. The residues of chlorpyrifos and deltamethrin were
      higher than the maximum residue limits (MRLs) at recommended preharvest intervals
      (PHIs) on head lettuce and Chinese broccoli treated with higher doses. The
      residues of methomyl on head lettuce also showed the same phenomenon. 

PMID- 24684566
TI  - Through thick and thin: tuning the threshold voltage in organic field-effect
      transistors.
AB  - Organic semiconductors (OSCs) constitute a class of organic materials containing
      densely packed, overlapping conjugated molecular moieties that enable charge
      carrier transport. Their unique optical, electrical, and magnetic properties have
      been investigated for use in next-generation electronic devices, from roll-up
      displays and radiofrequency identification (RFID) to biological sensors. The
      organic field-effect transistor (OFET) is the key active element for many of
      these applications, but the high values, poor definition, and long-term
      instability of the threshold voltage (V(T)) in OFETs remain barriers to
      realization of their full potential because the power and control circuitry
      necessary to compensate for overvoltages and drifting set points decrease OFET
      practicality. The drifting phenomenon has been widely observed and generally
      termed "bias stress." Research on the mechanisms responsible for this poor V(T)
      control has revealed a strong dependence on the physical order and chemical
      makeup of the interfaces between OSCs and adjacent materials in the OFET
      architecture. In this Account, we review the state of the art for tuning OFET
      performance via chemical designs and physical processes that manipulate V(T).
      This parameter gets to the heart of OFET operation, as it determines the voltage
      regimes where OFETs are either ON or OFF, the basis for the logical function of
      the devices. One obvious way to decrease the magnitude and variability of V(T) is
      to work with thinner and higher permittivity gate dielectrics. From the
      perspective of interfacial engineering, we evaluate various methods that we and
      others have developed, from electrostatic poling of gate dielectrics to molecular
      design of substituted alkyl chains. Corona charging of dielectric surfaces, a
      method for charging the surface of an insulating material using a constant high
      voltage field, is a brute force means of shifting the effective gate voltage
      applied to a gate dielectric. A gentler and more direct method is to apply
      surface voltage to dielectric interfaces by direct contact or postprocess
      biasing; these methods could also be adapted for high throughput printing
      sequences. Dielectric hydrophobicity is an important chemical property
      determining the stability of the surface charges. Functional organic monolayers
      applied to dielectrics, using the surface attachment chemistry made available
      from "self-assembled" monolayer chemistry, provide local electric fields without
      any biasing process at all. To the extent that the monolayer molecules can be
      printed, these are also suitable for high throughput processes. Finally, we
      briefly consider V(T) control in the context of device integration and
      reliability, such as the role of contact resistance in affecting this parameter.

PMID- 24684568
TI  - Understanding sensitivity: lessons learned from the legacy of Mary Ainsworth.
AB  - On the basis of extensive home observations, Ainsworth proposed that a mother's
      sensitivity to her infant's signals is the primary determinant of attachment
      security. Although subsequent research has found a relationship between
      sensitivity and attachment security, the effect sizes are much smaller than those
      reported by Ainsworth. In addition to the amount of observation time that might
      account for the effect size difference, we consider Ainsworth's focus on
      understanding the organizational structure of relationships. We coded 30 minute
      video records of interactions between 64 mother-infant dyads from semi-structured
      home observations conducted at 10 months of age. Coding consisted of writing a
      narrative summary of the interactions, annotating a completion of Ainsworth's
      rating scales of acceptance, accessibility, cooperation and sensitivity and then
      describing the mother's behavior using the Maternal Behaviour Q-set. Sensitivity
      scores derived from the Q-sort descriptions were robustly related (r = .65) to
      secure-insecure classifications in the Strange Situation conducted at 13 months.
      We reflect on the process of assessing Ainsworth's construct of sensitivity.

PMID- 24684567
TI  - The activation and inactivation of mature CD4 T cells: a case for peripheral self
      nonself discrimination.
AB  - The establishment of central tolerance to most self-antigens results in a
      repertoire of mature peripheral lymphocytes specific for foreign and peripheral
      self-antigens. The framework that single, mature lymphocytes are inactivated by
      antigen, whereas their activation requires lymphocyte cooperation, accounts for
      diverse observations and incorporates a mechanism of peripheral tolerance. This
      framework accounts for the generalizations that the sustained activation by
      antigen of most B cells and CD8 T cells requires CD4 T helper cells; in the
      absence of CD4 T cells, antigen can inactivate these B cells and CD8 T cells. In
      this sense, CD4 T cells are the guardians of the fate of most B cells and CD8 T
      cells when they encounter antigen. I argue here that the single
      lymphocyte/multiple-lymphocyte framework for the inactivation/activation of
      lymphocytes also applies to CD4 T cells. I consider within this framework a model
      for the activation/inactivation of CD4 T cells that is consistent with the large
      majority of contemporary observations, including significant clinical
      observations. I outline the grounds why I feel this model is more plausible than
      the contemporary and predominant pathogen-associated molecular pattern (PAMP) and
      Danger Models for CD4 T cell activation. These models are based upon what I
      consider the radical premise that self-nonself discrimination does not exist at
      the level of mature CD4 T cells. I explain why I feel this feature renders the
      PAMP and Danger Models somewhat implausible. The model I propose, in contrast, is
      conservative in that it embodies such a process of self-nonself discrimination.

PMID- 24684569
TI  - Testosterone therapy and cancer risk.
AB  - OBJECTIVE: To determine if testosterone therapy (TT) status modifies a man's risk
      of cancer. PATIENTS AND METHODS: The Urology clinic hormone database was queried
      for all men with a serum testosterone level and charts examined to determine TT
      status. Patient records were linked to the Texas Cancer Registry to determine the
      incidence of cancer. Men accrued time at risk from the date of initiating TT or
      the first office visit for men not on TT. Standardised incidence rates and time
      to event analysis were performed. RESULTS: In all, 247 men were on TT and 211 did
      not use testosterone. In all, 47 men developed cancer, 27 (12.8%) were not on TT
      and 20 (8.1%) on TT. There was no significant difference in the risk of cancer
      incidence based on TT (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.57
      1.9; P = 1.8). There was no difference in prostate cancer risk based on TT status
      (HR 1.2, 95% CI 0.54-2.50). CONCLUSION: There was no change in cancer risk
      overall, or prostate cancer risk specifically, for men aged >40 years using long
      term TT.

PMID- 24684570
TI  - The safety and efficacy of poly-L-lactic acid on sunken cheeks in Asians.
AB  - BACKGROUND: Poly-L-lactic acid (PLLA) is a biocompatible and biodegradable
      polymer device used for correction of facial contour deficiencies, with a gradual
      onset of effect that is maintained for up to 25 months. PLLA is currently widely
      used to correct age-related facial volume deficits in Asians. OBJECTIVES: We
      sought to evaluate the safety and long-term efficacy of PLLA on treating age
      related sunken cheeks in Asians. PATIENTS AND METHODS: This was a retrospective,
      single-center study of 11 subjects with age-related sunken cheeks who were
      treated with three sessions of PLLA, and then followed-up for 24 months. A
      questionnaire was used to evaluate patient satisfaction and the incidence of
      adverse reactions. RESULTS: Seven female and four male subjects with mild-to
      moderate age-related sunken cheeks were included in the study. The mean age of
      the subjects was 41.5 (range: 25-50). Overall, 90.9% of patients replied that
      they were either satisfied or very satisfied with the results at 24 months follow
      up; 91% of patients rated the volume correction to be good or excellent. Despite
      the high incidence of bruising (63.7%) and post-treatment nodules (27.3%), all
      subjects (100%) were willing to undergo the procedure again. CONCLUSION: PLLA has
      shown long-lasting effects in reversing age-related sunken cheeks in Asians, with
      high patient satisfaction. Special consideration should be made to minimize the
      side effects.

PMID- 24684571
TI  - New physiopathological and therapeutic approaches to diverticular disease: an
      update.
AB  - INTRODUCTION: Diverticular disease (DD) of the colon is a widespread disease,
      which shows worldwide increasing incidence and represents a significant burden
      for National Health Systems. The current guidelines claim that symptomatic
      uncomplicated DD (SUDD) has to be treated with spasmolithics and high-fiber diet,
      whereas both uncomplicated and complicated acute diverticulitis has to be treated
      with antibiotics. However, new physiopathological knowledge suggests that further
      treatment may be promising. AREAS COVERED: Pathogenetic and treatment studies on
      SUDD and acute diverticulitis published in PubMed, www.clinicaltrials.gov , and
      in the main International Congress were reviewed. EXPERT OPINION: Although
      absorbable antibiotics and 5-aminosalycilic acid seem to be effective in treating
      SUDD, their role in preventing diverticulitis recurrence is still under debate.
      Antibiotic use in managing acute diverticulitis is at least questionable, and use
      of probiotics seems to be promising but need further robust studies to confirm
      the preliminary results.

PMID- 24684572
TI  - Spring at last ....

PMID- 24684573
TI  - HPA-1a(-), 5b(-) platelets for use in neonatal alloimmune thrombocytopenia--from
      'Cinderella' product to standard component.

PMID- 24684574
TI  - Frequent human parvovirus B19 DNA occurrence and high seroprevalence in
      haemophilic patients from a non-metropolitan blood centre, Brazil.

PMID- 24684575
TI  - High-gain inverters based on WSe2 complementary field-effect transistors.
AB  - In this work, the operation of n- and p-type field-effect transistors (FETs) on
      the same WSe2 flake is realized,and a complementary logic inverter is
      demonstrated. The p-FET is fabricated by contacting WSe2 with a high work
      function metal, Pt, which facilities hole injection at the source contact. The n
      FET is realized by utilizing selective surface charge transfer doping with
      potassium to form degenerately doped n+ contacts for electron injection. An
      ON/OFF current ratio of >10(4) is achieved for both n- and p-FETs with similar ON
      current densities. A dc voltage gain of >12 is measured for the complementary
      WSe2 inverter. This work presents an important advance toward realization of
      complementary logic devices based on layered chalcogenide semiconductors for
      electronic applications. 

PMID- 24684577
TI  - Distinct regulation of tonsillar immune response in virus infection.
AB  - BACKGROUND: The relationships between tonsillar immune responses, and viral
      infection and allergy are incompletely known. OBJECTIVE: To study
      intratonsillar/nasopharyngeal virus detections and in vivo expressions of T-cell-
      and innate immune response-specific cytokines, transcription factors, and type
      I/II/III interferons in human tonsils. METHODS: Palatine tonsil samples were
      obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus-1,
      coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza
      virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The
      mRNA expression levels of IFN-alpha, IFN-beta, IFN-gamma, IL-10, IL-13, IL-17, IL
      28, IL-29, IL-37, TGF-beta, FOXP3, GATA3, RORC2, and Tbet were directly analyzed
      by quantitative RT-PCR. RESULTS: Fifty percentage of subjects reported allergy,
      59% had >=1 nasopharyngeal viruses, and 24% had >=1 intratonsillar viruses.
      Tonsillar virus detection showed a strong negative association with age;
      especially rhinovirus or parainfluenza virus detection showed positive
      association with IFN-gamma and Tbet expressions. IL-37 expression was positively
      associated with atopic dermatitis, whereas IFN-alpha, IL-13, IL-28, and Tbet
      expressions were negatively associated with allergic diseases. Network analyses
      demonstrated strongly polarized clusters of immune regulatory (IL-10, IL-17, TGF
      beta, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN-alpha, IFN-beta, IL-28, IL
      29) genes. These two clusters became more distinctive in the presence of viral
      infection or allergy. A negative correlation between antiviral cytokines and IL
      10, IL-17, IL-37, FOXP3, and RORC2 was observed only in the presence of viruses,
      and interestingly, IL-13 strongly correlated with antiviral cytokines.
      CONCLUSIONS: Tonsillar cytokine expression is closely related to existing viral
      infections, age, and allergic illnesses and shows distinct clusters between
      antiviral and immune regulatory genes.

PMID- 24684578
TI  - Comparative ultrastructure analysis of radiation-induced radioresistant laryngeal
      cancer hep-2 cell line.
AB  - Radioresistance is one of the main reasons for the failure of radiotherapy in
      laryngeal cancer. However, the mechanisms of radioresistance of tumor cells have
      remained elusive. This study was conducted to identify the ultrastructural
      changes of radiation-induced radioresistant laryngeal cancer hep-2 cell line.
      First, a radioresistant hep-2R cell line was generated after prolonged exposure
      to gamma-rays for 60 Gy (6 Gy/day, 2 days/week) and was confirmed by clonogenic
      assay. Next, the ultrastructural differences between hep-2R cells and hep-2 cells
      were compared by transmission electron microscopy. Finally, the results showed
      that hep-2R cells showed significant resistance to radiation compared with
      parental hep-2 cells. Increased cell nucleus atypia, more rough endoplasmic
      reticulum and less mitochondria were observed in hep-2R cells. The amount of
      microvilli of hep-2R was similar to hep-2 cell. In summary, these ultrastructural
      differences revealed the morphological mechanism that hep-2R cells had stronger
      radioresistance than hep-2 cells.

PMID- 24684576
TI  - Mn4Ca cluster in photosynthesis: where and how water is oxidized to dioxygen.

PMID- 24684579
TI  - Imitation (rather than core language) predicts pragmatic development in young
      children with ASD: a preliminary longitudinal study using CDI parental reports.
AB  - BACKGROUND: Research in the last decades has clearly pointed to the important
      role of language and communicative level when trying to understand developmental
      trajectories in children with autism spectrum disorders (ASD). AIMS: The purpose
      of this longitudinal study was to investigate whether (1) core language skills,
      measured as expressive vocabulary and grammar, and/or (2) pre-linguistic social
      communicative skills, including gestures and imitation abilities, drive pragmatic
      language development in young children with ASD. METHODS & PROCEDURES: We
      examined correlates and longitudinal predictors of pragmatic growth in a sample
      of 34 children with Autism spectrum disorder (ASD), whose parents were given
      parts of two MacArthur Communicative Developmental Inventories (CDI: Words &
      Gestures and CDI: Words & Sentences) for completion at two time points (at time 1
      the mean child age was 41 months, and at time 2 it was 54 months). A novel
      feature in this study is that the relevant parts from both CDI forms were
      included at both time points, allowing us to examine whether pre-linguistic
      social-communication skills (e.g. imitation and gesturing) and/or core language
      skills (i.e. grammar and vocabulary) predict pragmatic language growth. OUTCOMES
      & RESULTS: The results show that basically all pre-linguistic, linguistic and
      pragmatic skills were associated concurrently. When controlling for possible
      confounders and for the autoregressive effect, imitation skills predicted
      pragmatic growth over time, whereas core language did not. This could only have
      been shown by the use of both CDI forms. CONCLUSIONS & IMPLICATIONS: This
      preliminary study may be of both conceptual and methodological importance for
      research in the field of language and communication development in ASD. Imitation
      may play a pivotal role in the development of subsequent conversational pragmatic
      abilities in young children with ASD. Future research should be directed at
      unravelling the mechanisms underlying this association.

PMID- 24684580
TI  - Mono- and diboron corroles: factors controlling stoichiometry and hydrolytic
      reactivity.
AB  - The first example of a diboryl corrole complex, [(BF2)2(Br8T(4-F-P)C)](-) (Br8T(4
      F-P)C = trianion of 2,3,7,8,12,13,17,18-octabromo-5,10,15-tris(4
      fluorophenyl)corrole), has been isolated using the strongly electron-withdrawing
      and sterically crowded triaryl octabromocorrole ligand. Density functional theory
      (DFT) calculations show that the hydrolysis reaction producing the partially
      hydrolyzed complexes [B2OF2(Cor)](-) is more favored for the less sterically
      crowded triaryl corrole complexes. Monoboryl complexes BF2(H2Cor) (Cor =
      trianions of 5,10,15-triphenylcorrole (TPC), 5,10,15-tris(4-methylphenyl)corrole
      (T(4-CH3-P)C), 5,10,15-tris(4-trifluoromethylphenyl)corrole (T(4-CF3-P)C), and
      5,10,15-tris(pentafluorophenyl)corrole (TPFPC)) were prepared and characterized.
      The experimental data are consistent with an out-of-plane dipyrrin coordination
      mode for these complexes, and DFT optimizations suggest that internal BF...HN
      hydrogen bonding may be significant in stabilizing these complexes. Further
      examples of the anionic diboron corrole [B2OF2(Cor)](-) containing the electron
      withdrawing 5,10,15-tris(pentafluorophenyl)corrole (TPFPC) and the sterically
      hindered 10-(4-methoxyphenyl)-5,15-dimesitylcorrole (Mes2(4-MeOP)C) trianions are
      reported. 

PMID- 24684581
TI  - Pediatric Cranio-spinal Axis Irradiation: Comparison of Radiation-induced
      Secondary Malignancy Estimations Based on Three Methods of Analysis for Three
      Different Treatment Modalities.
AB  - Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many
      central nervous system (CNS) diseases, but due to the life expectancies and
      quality of life expectations for children, the minimization of the risk for
      radiation-induced secondary malignancies must be a high priority. This study
      compared the estimated CSI-induced secondary malignancy risks of three radiation
      therapy modalities using three different models. Twenty-four (n = 24) pediatric
      patients previously treated with CSI for tumors of the CNS were planned using
      three different treatment modalities: three-dimensional conformal radiation
      therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan
      was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined
      as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as
      well as the dose volume histograms (DVH) of specific organs were analyzed for
      secondary malignancy risk according to three different methods: the effective
      dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic
      (LQ) models. Using the EDE model, the average secondary risk was highest for the
      3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The
      ERR model showed similarly that the 3D-CRT plans had considerably higher risk
      (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and
      7.07%, respectively). The LQ model requires organ-specific cell survival
      parameters, which for the lungs, heart, and breast relevant values were found and
      applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and
      2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk
      for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75,
      6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three
      methods of secondary malignancy estimation, the 3D-CRT plans produced highest
      radiation-induced secondary malignancy risk, and the VMAT and Tomotherapy plans
      had nearly equal risk. Pediatric patients must be treated with reducing long term
      sequelae as a priority. 

PMID- 24684582
TI  - Influence of velocity on variability in gait kinematics: implications for
      recognition in forensic science.
AB  - Closed circuit television (CCTV) footage is often available from crime scenes and
      may be used to compare perpetrators with suspects. Usually, the footage comprises
      incomplete gait cycles at different velocities, making gait pattern
      identification from crimes difficult. This study investigated the concurrence of
      joint angles throughout a gait cycle at three different velocities (3.0, 4.5, 6.0
      km/h). Six datasets at each velocity were collected from 16 men. A variability
      range VR throughout the gait cycle at each velocity for each joint angle for each
      person was calculated. The joint angles at each velocity were compared pairwise,
      and whenever this showed values within the VR of this velocity, the case was
      positive. By adding the positives throughout the gait cycle, phases with high and
      low concurrences were located; peak concurrence was observed at mid-stance phase.
      Striving for the same velocity for the suspect and perpetrator is recommended. 

PMID- 24684583
TI  - Pneumothoraces in Birt-Hogg-Dube syndrome compared to smoking related blebs.

PMID- 24684584
TI  - External validation of the Briganti nomogram to estimate the probability of
      specimen-confined disease in patients with high-risk prostate cancer.
AB  - OBJECTIVE: To establish an external validation of the updated nomogram from
      Briganti et al., which provides estimates of the probability of specimen-confined
      disease using the variables age, prostate-specific antigen (PSA), clinical stage
      and biopsy Gleason score in preoperatively defined high-risk prostate cancer
      (PCa). PATIENTS AND METHODS: The study included 523 patients with high-risk PCa,
      as defined by d'Amico classification, undergoing radical prostatectomy (RP) and
      bilateral lymph node dissection in one of two academic centres between 1990 and
      2013. Specimen-confined disease was defined as pT2-pT3a node-negative PCa with
      negative surgical margins. The receiver-operator characteristic (ROC) curve was
      obtained to quantify the overall accuracy (area under the curve [AUC]) of the
      model in predicting specimen-confined disease. A calibration curve was then
      constructed to illustrate the relationship between the risk estimates obtained by
      the model (x-axis) and the observed proportion of specimen-confined disease (y
      axis). The Kaplan-Meier method was used to assess biochemical recurrence (BCR)
      free survival. RESULTS: Patients' median age and PSA level were 64 years and 21
      ng/mL, respectively. The definition of high-risk PCa was based on PSA level only
      in 38.3%, a biopsy Gleason score >7 in 34.5%, a clinical stage >T2b in 6.9%, or a
      combination of these two or three factors in 20.3% of patients. Positive surgical
      margins were observed in 43.6%, with a rate of 14.8% in pT2 cancers and lymph
      node metastasis in 12.1% of patients. pT stage was pT0 in 0.9%, pT2 in 28.9%,
      pT3a in 37.5% and pT3b-4 in 32.7% of patients. Overall, 44.4% of patients (N =
      232) had specimen-confined disease. PSA and cT stage were independently
      predictive of specimen-confined disease. The median (range) 2-, 5-, and 8-year
      BCR-free survival rates were significantly higher in specimen-confined disease as
      compared with non-specimen-confined disease: 80.87 (73.67-86.29) vs 37.55 (30.64
      44.44)%, 63.53 (52.37-72.74) vs 26.93 (19.97-34.36)% and 55.08 (41.49-66.74) vs
      19.52 (12.50-27.70)%, respectively (P < 0.001). The ROC curve analysis showed
      relevant accuracy of the model (AUC 0.6470, 95% CI 0.60-0.69) although the
      calibration plot suggested that, for risks ranging from 0.3 to 0.5, the odds of
      extracapsular extension were underestimated. CONCLUSIONS: This external
      validation of the Briganti nomogram shows relevant accuracy, although the
      relative imprecision for intermediate risk may limit its clinical relevance. Our
      follow-up findings confirm the large proportion of specimen-confined PCa with
      good oncological outcomes in this heterogeneous subgroup of patients with high
      risk PCa.

PMID- 24684585
TI  - Update to the general amber force field for small solutes with an emphasis on
      free energies of hydration.
AB  - An approach to a straightforward reparametrization of the general AMBER force
      field (GAFF) for small organic solutes and druglike compounds is presented. The
      parametrization is based on specific pair interactions between the solvent and
      the solute, namely, the interactions between the constituting atoms of the solute
      and the oxygen of water were tuned in order to reproduce experimental hydration
      free energies for small model compounds. The key of the parametrization was to
      abandon the Lorentz-Berthelot combination rules for the van der Waals
      interactions. These parameters were then used for larger solutes in order to
      validate the newly derived pair interactions. In total close to 600 hydration
      free energies are computed, ranging from simple alkanes to multifunctional drug
      compounds, and compared to experimental data. The results show that the proposed
      parameters work well in describing the interactions between the solute and the
      solvent and that the agreement in absolute numbers is good. This modified version
      of GAFF is a good candidate for computing and predicting hydration free energies
      on a large scale, which has been a long-sought goal of computational chemists and
      can be used in rational drug design. 

PMID- 24684587
TI  - Evaporative assembly of MEH-PPV rings using mixed solvents at the air/water
      interface.
AB  - Controlling the morphology of conjugated polymers has recently attracted
      considerable attention because of their applications in photovoltaic (PV) devices
      and organic light-emitting diodes (OLEDs). Here, we describe the self-assembly of
      a common conjugated polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4
      phenylenevinylene] (MEH-PPV), into ringlike structures via solvent evaporation on
      an air/water interface. The films are monitored using Brewster angle microscopy
      (BAM) and transferred onto a solid substrate by either the Langmuir-Blodgett (LB)
      or the Langmuir-Schaefer (LS) method and further characterized by atomic force
      microscopy (AFM). The morphology of the MEH-PPV thin film at the air/water
      interface can be controlled by the spreading solvent. By mixing solvents of
      varying spreading coefficients and evaporation rates, such as chloroform and
      chlorobenzene, MEH-PPV can be assembled into micrometer-sized ring structures.
      The optical properties of these MEH-PPV ring structures are also characterized.
      Lastly, MEH-PPV can be used as a soft template to organize microscale structures
      of nanoparticles. 

PMID- 24684586
TI  - Stability of fathers' representations of their infants during the transition to
      parenthood.
AB  - Studies investigating fathers' roles in child development have focused on a range
      of different aspects. However, few studies have focused on the early father
      infant relationship, which already emerges before the child is born. The aim of
      this study is to examine the concordance of fathers' representations of their
      children during the transition to parenthood. The influences of demographic
      variables, psychological wellbeing, and personality on the stability of these
      representations are investigated. At 26 weeks gestational age and when infants
      were six months old, fathers (N = 243) completed questionnaires and the Working
      Model of the Child Interview during a home visit. A strong association was found
      between fathers' prenatal and postnatal representations. First-time fathers more
      often had balanced representations than fathers who already had children.
      Furthermore, agreeable fathers were more likely to evolve from a non-balanced
      prenatal representation to a balanced postnatal representation. 

PMID- 24684588
TI  - Hybrid operation for type B aortic dissection involving distal aortic arch.
AB  - OBJECTIVES: To retrospectively summarize clinical experiences and mid-term follow
      up outcomes of hybrid operation for Type B aortic dissection involving the distal
      arch. METHODS: From February 2009 to April 2013, 15 consecutive patients (6 males
      and 9 females) with Type B aortic dissection (acute, n = 10; chronic, n = 5)
      involving the distal aortic arch underwent a hybrid operation. RESULTS: The
      patients' median age was 62 (68-44) years. The median hospital stay was 14 (19
      11) days. The hybrid procedure was performed in 15 patients comprising seven in
      zone 1 and eight in zone 2. Technical success was achieved in 100% and no case of
      paraplegia was reported. Thirty-day mortality and stroke were 0%. At a median
      follow-up of 12 months (range, 4-52 months), a stroke and death occurred in one
      patient not associated with an endograft complication. At follow-up, the overall
      mortality was 6.7% (1 of 15). A computed tomography scan was performed in 13 of
      15 patients and thrombus formation was observed in the descending aortic false
      lumen excluded by the stented graft in most patients. The overall late endoleak
      rate was 7.7% (1 of 13); retrograde dissection occurred in no patient. There are
      no differences between acute and chronic aortic dissection or proximal landing
      zone 1 and landing zone 2 except for proximal endograft dimension. CONCLUSIONS:
      Hybrid operation for Type B aortic dissection involving the distal aortic arch
      appears safe and effective at mid-term follow-up and may extend the application
      of endovascular repair in the treatment of this pathology.

PMID- 24684589
TI  - Eotaxin-3 activates the Smad pathway through the transforming growth factor beta
      1 in chronic subdural hematoma outer membranes.
AB  - Chronic subdural hematoma (CSDH) is considered to be an inflammatory disease.
      Eosinophils are frequently expressed in the outer membrane of CSDH and are major
      sources of transforming growth factor beta (TGF-beta). The mothers against
      decapentaplegic (Smad)-signaling pathway, which is activated by TGF-beta, has
      been shown to be involved with fibrosis. In the present study, we compared the
      concentrations of eotaxin-3, eosinophil-specific chemoattractant, and TGF-beta
      between CSDH fluid and cerebrospinal fluid (CSF) from control patients. We also
      explored the expression of the Smad-signaling pathway in the outer membrane of
      CSDH. Eight patients whose outer membrane and 12 whose CSDH fluid were
      successfully obtained during trepanation surgery were included in the study.
      Concentrations of eotaxin-3 and TGF-beta were measured by enzyme immunoassay
      kits. Expression levels of Smad2, phosphorylated Smad3, Smad3, Smad4, and actin
      were examined by Western blot analysis. In addition, expression of Smad3 was also
      examined by immunohistochemistry. Concentrations of eotaxin-3 and TGF-beta in
      CSDH fluid were significantly higher than those in CSF. Smad2, Smad3,
      phosphorylated Smad3, and Smad4 were detected in all cases. Smad3 was shown to be
      present in fibroblasts. These findings indicate that eotaxin-3 is expressed in
      CSDH fluid, inducing eosinophils into the outer membrane and resulting in
      elevation of TGF-beta with the Smad pathway activated by TGF-beta. These data
      suggest a potential mechanism for CSDH formation and growth.

PMID- 24684590
TI  - A retrospective study on laser treatment of nevus of Ota in Chinese children--a
      seven-year follow-up.
AB  - OBJECTIVE: To retrospectively study laser treatment of nevus of Ota in children.
      METHODS: Clinically analyzing characteristics, effects, side effects, and
      recurrence of a 104 cases of nevus of Ota in children under 12 years, including
      32 boys and 72 girls. RESULTS: After seven treatments, cure rate of lesion color
      fading and area reducing were 79.81% and 75.96%, respectively. After 10
      treatments, both of the two cure rates were 96.15%. Later the cure rate was
      constant with even more treatments. The younger the first treating age, the
      lesser the treatments are. The younger the age of onset, the higher the relapse
      after clearance. CONCLUSION: Nevus of Ota should be treated as early as possible
      to reach better efficacy with less treatments. The younger the onset age, the
      easier it recurs.

PMID- 24684591
TI  - Impulsivity as a predictor of treatment outcome in substance use disorders:
      review and synthesis.
AB  - ISSUES: Impulsivity is a widely studied personality trait and research construct
      that has been implicated as a risk factor for substance use, including initiating
      and continuing use. However, relatively few studies have examined impulsivity as
      a predictor of treatment outcome. Because impulsivity has been operationalised in
      many different ways, cross-comparisons of empirical studies have been difficult.
      APPROACH: The PubMed database was searched in September 2013. Reference lists of
      papers retrieved from this search were also manually scanned for additional
      resources. Studies were included if they presented data that assessed impulsivity
      as a predictor of treatment outcomes. KEY FINDINGS: The body of literature
      reviewed in this paper suggests that higher pretreatment impulsivity, regardless
      of how it is measured, usually is associated with poorer treatment outcomes.
      Recent data indicate that some psychosocial and pharmacological treatments may
      directly impact impulsivity and thus represent an interesting avenue for further
      research. CONCLUSIONS: Impulsivity appears to be a key predictor of substance use
      treatment outcomes and warrants more attention in the improvement of treatment
      outcomes. Suggestions for future research on the role of impulsivity in substance
      use treatment are provided.

PMID- 24684593
TI  - The role of thiopurine metabolite monitoring in inflammatory bowel disease.
AB  - Thiopurines are the mainstay of medical management in inflammatory bowel disease
      (IBD), especially in the maintenance of disease remission. Given the limited IBD
      armamentarium it is important to optimize each therapy before switching to an
      alternative drug. Conventional weight based dosing of thiopurines in IBD leads to
      intolerance or inefficacy in many patients. More recently increased knowledge of
      their metabolism has allowed for dose optimization using thiopurine metabolite
      levels, namely 6-thioguanine nucleotides and 6-methylmercaptopurine, with the
      potential for improved outcomes in patients with IBD. This review will outline
      the current understanding of thiopurine metabolism and pharmacogenomics and will
      describe the clinical application of this knowledge in the optimization of
      thiopurines in individual patients. 

PMID- 24684592
TI  - On the mechanism determining the TH1/TH2 phenotype of an immune response, and its
      pertinence to strategies for the prevention, and treatment, of certain infectious
      diseases.
AB  - It is well recognized that the physiological/pathological consequences of an
      immune response, against a foreign or a self-antigen, are often critically
      dependent on the class of immunity generated. Here we focus on how antigen
      interacts with the cells of the immune system to determine whether antigen
      predominantly generates Th1 or Th2 cells. We refer to this mechanism as the
      'decision criterion' controlling the Th1/Th2 phenotype of the immune response. A
      plausible decision criterion should account for the variables of immunization
      known to affect the Th1/Th2 phenotype of the ensuing immune response. Documented
      variables include the nature of the antigen, in terms of its degree of
      foreignness, the dose of antigen and the time after immunization at which the
      Th1/Th2 phenotype of the immune response is assessed. These are quantitative
      variables made at the level of the system. In addition, the route of immunization
      is also critical. I describe a quantitative hypothesis as to the nature of the
      decision criterion, referred to as the Threshold Hypothesis. This hypothesis
      accounts for the quantitative variables of immunization known to affect the
      Th1/Th2 phenotype of the immune response generated. I suggest and illustrate how
      this is not true of competing, contemporary hypotheses. I outline studies testing
      predictions of the hypothesis and illustrate its potential utility in designing
      strategies to prevent or treat medical situations where a predominant Th1
      response is required to contain an infection, such as those caused by HIV-1 and
      by Mycobacterium tuberculosis, or to contain cancers.

PMID- 24684594
TI  - Supramolecular polymers constructed from macrocycle-based host-guest molecular
      recognition motifs.
AB  - CONSPECTUS: Supramolecular polymers, fabricated via the combination of
      supramolecular chemistry and polymer science, are polymeric arrays of repeating
      units held together by reversible, relatively weak noncovalent interactions. The
      introduction of noncovalent interactions, such as hydrogen bonding, aromatic
      stacking interactions, metal coordination, and host-guest interactions, endows
      supramolecular polymers with unique stimuli responsiveness and self-adjusting
      abilities. As a result, diverse monomer structures have been designed and
      synthesized to construct various types of supramolecular polymers. By changing
      the noncovalent interaction types, numbers, or chemical structures of functional
      groups in these monomers, supramolecular polymeric materials can be prepared with
      tailored chemical and physical properties. In recent years, the interest in
      supramolecular polymers has been extended from the preparation of intriguing
      topological structures to the discoveries of potential applications as functional
      materials. Compared with traditional polymers, supramolecular polymers show some
      advantages in the fabrication of reversible or responsive materials. The
      development of supramolecular polymers also offers a platform to construct
      complex and sophisticated materials with a bottom-up approach. Macrocylic hosts,
      including crown ethers, cyclodextrins, calixarenes, cucurbiturils, and
      pillararenes, are the most commonly used building blocks in the fabrication of
      host-guest interaction-based supramolecular polymers. With the introduction of
      complementary guest molecules, macrocylic hosts demonstrate selective and stimuli
      responsive host-guest complexation behaviors. By elaborate molecular design, the
      resultant supramolecular polymers can exhibit diverse structures based on the
      self-selectivity of host-guest interactions. The introduction of reversible host
      guest interactions can further endow these supramolecular polymers with
      interesting and fascinating chemical/physical properties, including stimuli
      responsiveness, self-healing, and environmental adaptation. It has been reported
      that macrocycle-based supramolecular polymers can respond to pH change,
      photoirradition, anions, cations, temperature, and solvent. Macrocycle-based
      supramolecular polymers have been prepared in solution, in gel, and in the solid
      state. Furthermore, the solvent has a very important influence on the formation
      of these supramolecular polymers. Crown ether- and pillararene-based
      supramolecular polymers have mainly formed in organic solvents, such as
      chloroform, acetone, and acetonitrile, while cyclodextrin- and cucurbituril-based
      supramolecular polymerizations have been usually observed in aqueous solutions.
      For calixarenes, both organic solvents and water have been used as suitable media
      for supramolecular polymerization. With the development of supramolecular
      chemistry and polymer science, various methods, such as nuclear magnetic
      resonance spectroscopy, X-ray techniques, electron microscopies, and theoretical
      calculation and computer simulation, have been applied for characterizing
      supramolecular polymers. The fabrication of macrocycle-based supramolecular
      polymers has become a currently hot research topic. In this Account, we summarize
      recent results in the investigation of supramolecular polymers constructed from
      macrocycle-based host-guest molecular recognition motifs. These supramolecular
      polymers are classified based on the different macrocycles used in them. Their
      monomer design, structure control, stimuli-responsiveness, and applications in
      various areas are discussed, and future research directions are proposed. It is
      expected that the development of supramolecular polymers will not only change the
      way we live and work but also exert significant influence on scientific research.

PMID- 24684596
TI  - Vitamin E levels in soybean (Glycine max (L.) Merr.) expressing a p
      hydroxyphenylpyruvate gene from oat (Avena sativa L.).
AB  - The enzyme p-hydroxyphenylpyruvate dioxygenase (HPPD) is ubiquitous in plants and
      functions in the tyrosine catabolic pathway, resulting in the formation of
      homogentisate. Homogentisate is the aromatic precursor of all plastoquinones and
      tocochromanols, including tocopherols and tocotrienols. Soybean (Glycine max (L.)
      Merr.) has been genetically modified to express the gene avhppd-03 that encodes
      the protein AvHPPD-03 derived from oat (Avena sativa L.). The AvHPPD-03 isozyme
      has an inherent reduced binding affinity for mesotrione, a herbicide that
      inhibits the wild-type soybean HPPD enzyme. Expression of avhppd-03 in soybean
      plants confers a mesotrione-tolerant phenotype. Seeds from three different avhppd
      03-expressing soybean events were quantitatively assessed for content of eight
      vitamin E isoforms. Although increased levels of two tocopherol isoforms were
      identified for each of the three soybean events, they were within, or not
      substantially different from, the ranges of these isoforms found in nontransgenic
      soybean varieties. The increases of these tocopherols in the avhppd-03-expressing
      soybean events may have a slight benefit with regard to vitamin E nutrition but,
      given the commercial processing of soybeans, are unlikely to have a material
      impact on human nutrition with regard to vitamin E concentrations in soybean oil.

PMID- 24684595
TI  - The exochelins of pathogenic mycobacteria: unique, highly potent, lipid- and
      water-soluble hexadentate iron chelators with multiple potential therapeutic
      uses.
AB  - SIGNIFICANCE: Exochelins are lipid- and water-soluble siderophores of
      Mycobacterium tuberculosis with unique properties that endow them with
      exceptional pharmacologic utility. Exochelins can be utilized as probes to
      decipher the role of iron in normal and pathological states, and, since they
      rapidly cross cell membranes and chelate intracellular iron with little or no
      toxicity, exochelins are potentially useful for the treatment of a number of iron
      dependent pathological phenomena. RECENT ADVANCES: In animal models, exochelins
      have been demonstrated to have promise for the treatment of transfusion-related
      iron overload, restenosis after coronary artery angioplasty, cancer, and
      oxidative injury associated with acute myocardial infarction and transplantation.
      CRITICAL ISSUES: To be clinically effective, iron chelators should be able to
      rapidly enter cells and chelate iron at key intracellular sites. Desferri
      exochelins, and other lipid-soluble chelators, can readily cross cell membranes
      and remove intracellular free iron; whereas deferoxamine, which is lipid
      insoluble, cannot do so. Clinical utility also requires that the chelators be
      nontoxic, which, we hypothesize, includes the capability to prevent iron from
      catalyzing free radical reactions which produce *OH or other reactive oxygen
      species. Lipid-soluble iron chelators currently available for clinical
      application are bidentate (deferiprone) or tridentate (desferasirox) molecules
      that do not block all six sites on the iron molecule capable of catalyzing free
      radical reactions. In contrast, desferri-exochelins are hexadentate molecules,
      and by forming a one-to-one binding relationship with iron, they prevent free
      radical reactions. FUTURE DIRECTIONS: Clinical studies are needed to assess the
      utility of desferri-exochelins in the treatment of iron-dependent pathological
      disorders.

PMID- 24684597
TI  - Site-specific thermodynamic stability and unfolding of a de novo designed protein
      structural motif mapped by 13C isotopically edited IR spectroscopy.
AB  - The mechanism of protein folding remains poorly understood, in part due to
      limited experimental information available about partially folded states.
      Isotopically edited infrared (IR) spectroscopy has emerged as a promising method
      for studying protein structural changes with site-specific resolution, but its
      full potential to systematically probe folding at multiple protein sites has not
      yet been realized. We have used (13)C isotopically edited IR spectroscopy to
      investigate the site-specific thermal unfolding at seven different locations in
      the de novo designed helix-turn-helix protein alphatalpha. As one of the few
      stable helix-turn-helix motifs, alphatalpha is an excellent model for studying
      the roles of secondary and tertiary interactions in folding. Circular dichroism
      (CD) experiments on the full alphatalpha motif and its two peptide fragments show
      that interhelical tertiary contacts are critical for stabilization of the
      secondary structure. The site-specific thermal unfolding probed by (13)C
      isotopically edited IR is likewise consistent with primarily tertiary
      stabilization of the local structure. The least thermally stable part of the
      alphatalpha motif is near the turn where the interhelical contacts are rather
      loose, while the motif's center with best established core packing has the
      highest stability. Similar correlation between the local thermal stability and
      tertiary contacts was found previously for a naturally occurring helix-turn-helix
      motif. These results underline the importance of native-like tertiary stabilizing
      interactions in folding, in agreement with recent state-of-the art folding
      simulations as well as simplified, native-centric models. 

PMID- 24684598
TI  - microRNA-200a inhibits cell proliferation by targeting mitochondrial
      transcription factor A in breast cancer.
AB  - microRNAs (miRNAs) are endogenous 19-25 nucleotide noncoding single-stranded RNAs
      that regulate gene expression by blocking the translation or decreasing the
      stability of mRNAs. In this study, we showed that miR-200a expression levels were
      decreased while mitochondrial transcription factor A (TFAM) mRNA expression
      levels were increased in breast cancer (BC) tissues and cell lines, and
      identified TFAM as a novel direct target of miR-200a. Overexpression of miR-200a
      suppressed TFAM protein expression, mtDNA copy number, and attenuated cell
      proliferation. Forced expression of TFAM can partly rescue the inhibitory effect
      of miR-200a in the cells. Taken together, these findings will shed light on the
      role and mechanism of miR-200a in regulating BC cells growth and mtDNA copy
      number via miR-200a/TFAM axis, and miR-200a may serve as a potential therapeutic
      target in BC in the future. 

PMID- 24684600
TI  - A protocol for a pragmatic randomized controlled trial evaluating outcomes of
      emergency nurse practitioner service.
AB  - AIM: To evaluate emergency nurse practitioner service effectiveness on outcomes
      related to quality of care and service responsiveness. BACKGROUND: Increasing
      service pressures in the emergency setting have resulted in the adoption of
      service innovation models; the most common and rapidly expanding of these is the
      emergency nurse practitioner. The delivery of high quality patient care in the
      emergency department is one of the most important service indicators to be
      measured in health services today. The rapid uptake of emergency nurse
      practitioner service in Australia has outpaced the capacity to evaluate this
      model in outcomes related to safety and quality of patient care. DESIGN:
      Pragmatic randomized controlled trial at one site with 260 participants. METHODS:
      This protocol describes a definitive prospective randomized controlled trial,
      which will examine the impact of emergency nurse practitioner service on key
      patient care and service indicators. The study control will be standard emergency
      department care. The intervention will be emergency nurse practitioner service.
      The primary outcome measure is pain score reduction and time to analgesia.
      Secondary outcome measures are waiting time, number of patients who did not wait,
      length of stay in the emergency department and representations within 48 hours.
      DISCUSSION: Scant research enquiry evaluating emergency nurse practitioner
      service on patient effectiveness and service responsiveness exists currently.
      This study is a unique trial that will test the effectiveness of the emergency
      nurse practitioner service on patients who present to the emergency department
      with pain. The research will provide an opportunity to further evaluate emergency
      nurse practitioner models of care and build research capacity into the workforce.
      Trial registration details: Australian and New Zealand Clinical Trials Registry
      dated 18th August 2013, ACTRN12613000933752.

PMID- 24684601
TI  - The pharmacokinetics of a single oral or rectal dose of concurrently administered
      isoniazid, rifampin, pyrazinamide, and ethambutol in Asian elephants (Elephas
      maximus).
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, is a disease of concern in
      captive Asian elephants (Elephas maximus). Treatment for tuberculosis in
      elephants utilizes multidrug protocols combining isoniazid, rifampin,
      pyrazinamide, and/or ethambutol. In this study, a single, coformulated dose of
      isoniazid 5 mg/kg, rifampin 10 mg/kg, pyrazinamide 30 mg/kg, and ethambutol 30
      mg/kg was administered orally to six Asian elephants, and rectally to five
      elephants using a cross-over design. Blood samples were collected serially over
      24 h. Pyrazinamide and ethambutol concentrations were determined using validated
      gas chromatography assays. Isoniazid and rifampin concentrations were determined
      using validated high-performance liquid chromatography assays. Rectal isoniazid
      produced an earlier Tmax compared with oral administration. Oral isoniazid
      resulted in a comparatively lower Cmax , but higher AUC values compared with
      rectal isoniazid. Oral rifampin and oral ethambutol were well absorbed while
      rectal rifampin was not. Oral pyrazinamide produced comparatively higher Cmax and
      AUC values compared with rectal pyrazinamide. Results of this study indicate that
      currently recommended therapeutic monitoring sample collection times for rectal
      isoniazid and oral rifampin do not provide an accurate assessment of exposure for
      these drugs. This study demonstrates notable individual variability, indicating
      that dosing of these medications requires individual monitoring and provides
      additional information to guide the clinician when treating elephants. 

PMID- 24684602
TI  - Face-to-face with anti-inflammatory therapy for rosacea.
AB  - In the past, our understanding of rosacea has been inadequate and limited to
      descriptions of factors that exacerbate and improve the disease. While the
      pathophysiology of rosacea is complex and multifactorial, cathelicidin peptides
      have emerged as key players in the pathogenesis of this common dermatological
      disorder. This article correlates recent findings in abnormal cathelicidin
      production and proteolytic processing in rosacea with therapeutic actions of
      current treatment options and, in this way, highlights potential points of
      intervention for the development of efficient therapeutic alternatives.

PMID- 24684603
TI  - Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized
      controlled trial.
AB  - This trial was designed to test the safety and effectiveness of transcutaneous
      auricular vagus nerve stimulation (ta-VNS) for patients with refractory
      epilepsy.Pre-trial:144 patients were randomly assigned to ta-VNS group (n=98) or
      transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group
      (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24
      weeks of treatment,the patients were evaluated according to the Modified Engel
      Scale (four classes). After 8 weeks,according to the medical ethic design,
      patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks'
      treatment 41.0% and 27.5% of patients from ta-VNS and tn-VNS groups,
      respectively, experienced reduction in seizure frequency that reached I, II and
      III levels according to the standards of the Modified Engel Scale compared with
      the baselines, indicating significant difference in seizure reduction between the
      two groups. After 24 weeks of treatment, ta-VNS patients had a 47.7% reduction,
      and tn-VNS, with an additional 16 weeks of treatment, reached 47.5% in reduction.
      After 8 weeks' treatment, the percentages of average seizure frequency in ta-VNS
      and tn-VNS were reduced by 42.6% and 11.5% respectively, providing a
      statistically significant difference in the results between the two groups
      (P<0.05). In addition, there were significant improvements in
      electroencephalograph (EEG) and the quality of daily life of the patients after
      treatment.The results show that this ta-VNS treatment can effectively reduce the
      frequency of seizures and improve the patient's quality of life. This may be an
      effective treatment for refractory epilepsy. At the same time,it is also
      safe,economic, and widely applicable.

PMID- 24684604
TI  - Eggplant and related species are promising genetic resources to dissect the plant
      immune response to Pseudomonas syringae and Xanthomonas euvesicatoria and to
      identify new resistance determinants.
AB  - The apparent lack of durability of many resistance (R) genes highlights the need
      for the constant identification of new genetic sources of resistance for the
      breeding of new disease-resistant crop cultivars. To this end, we screened a
      collection of accessions of eggplant and close relatives for resistance against
      Pseudomonas syringae pv. tomato (Pto) and Xanthomonas euvesicatoria (Xeu), foliar
      plant pathogens of many solanaceous crops. Both pathogens caused substantial
      disease on most genotypes of eggplant and its relatives. Promisingly, however,
      some of the genotypes were fully or partially resistant to either of the
      pathogens, suggesting the presence of effective resistance determinants in these
      genotypes. Segregation of resistance to the growth of Xeu following infiltration
      in F2 progeny from a cross of a resistant and susceptible genotype suggests that
      resistance to Xeu is inherited as a multigenic trait. With regard to Pto, a
      mutant strain lacking all 28 functional type III secreted effectors, and a
      Pseudomonas fluorescens strain expressing a P. syringae type III secretion system
      (T3SS), both elicit a strong cell death response on most eggplant lines. Several
      genotypes thus appear to harbour a mechanism for the direct recognition of a
      component of the T3SS. Therefore, eggplant and its close relatives are promising
      resources to unravel novel aspects of plant immunity and to identify new
      candidate R genes that could be employed in other Solanaceae in which Xeu and Pto
      cause agriculturally relevant diseases.

PMID- 24684605
TI  - Synthesis and structure determination of a new Au(20) nanocluster protected by
      tripodal tetraphosphine ligands.
AB  - We report the synthesis and structure determination of a new Au20 nanocluster
      coordinated by four tripodal tetraphosphine (PP3) ligands {PP3 = tris[2
      (diphenylphosphino)ethyl]phosphine}. Single-crystal X-ray crystallography and
      electrospray ionization mass spectrometry show that the cluster assembly can be
      formulated as [Au20(PP3)4]Cl4. The Au20 cluster consists of an icosahedral Au13
      core and a seven-Au-atom partial outer shell arranged in a local C3 symmetry. One
      PP3 ligand coordinates to four Au atoms in the outer shell, while the other three
      PP3 ligands coordinate to one Au atom from the outer shell and three Au atoms
      from the surface of the Au13 core, giving rise to an overall chiral 16-electron
      Au cluster core with C3 symmetry. 

PMID- 24684606
TI  - Single-cell control of initial spatial structure in biofilm development using
      laser trapping.
AB  - Biofilms are sessile communities of microbes that are spatially structured by an
      embedding matrix. Biofilm infections are notoriously intractable. This arises, in
      part, from changes in the bacterial phenotype that result from spatial structure.
      Understanding these interactions requires methods to control the spatial
      structure of biofilms. We present a method for growing biofilms from initiating
      cells whose positions are controlled with single-cell precision using laser
      trapping. The native growth, motility, and surface adhesion of positioned
      microbes are preserved, as we show for model organisms Pseudomonas aeruginosa and
      Staphylococcus aureus. We demonstrate that laser-trapping and placing bacteria on
      surfaces can reveal the effects of spatial structure on bacterial growth in early
      biofilm development. 

PMID- 24684607
TI  - Evaluating children's conservation biology learning at the zoo.
AB  - Millions of children visit zoos every year with parents or schools to encounter
      wildlife firsthand. Public conservation education is a requirement for membership
      in professional zoo associations. However, in recent years zoos have been
      criticized for failing to educate the public on conservation issues and related
      biological concepts, such as animal adaptation to habitats. I used matched pre-
      and postvisit mixed methods questionnaires to investigate the educational value
      of zoo visits for children aged 7-15 years. The questionnaires gathered
      qualitative data from these individuals, including zoo-related thoughts and an
      annotated drawing of a habitat. A content analysis of these qualitative data
      produced the quantitative data reported in this article. I evaluated the relative
      learning outcomes of educator-guided and unguided zoo visits at London Zoo, both
      in terms of learning about conservation biology (measured by annotated drawings)
      and changing attitudes toward wildlife conservation (measured using thought
      listing data). Forty-one percent of educator-guided visits and 34% of unguided
      visits resulted in conservation biology-related learning. Negative changes in
      children's understanding of animals and their habitats were more prevalent in
      unguided zoo visits. Overall, my results show the potential educational value of
      visiting zoos for children. However, they also suggest that zoos' standard
      unguided interpretive materials are insufficient for achieving the best outcomes
      for visiting children. These results support a theoretical model of conservation
      biology learning that frames conservation educators as toolmakers who develop
      conceptual resources to enhance children's understanding of science.

PMID- 24684608
TI  - Extinction of an instrumental response: a cognitive behavioral assay in Fmr1
      knockout mice.
AB  - Fragile X (FX) is the most common genetic cause of intellectual disability and
      autism. Previous studies have shown that partial inhibition of metabotropic
      glutamate receptor signaling is sufficient to correct behavioral phenotypes in a
      mouse model of FX, including audiogenic seizures, open-field hyperactivity and
      social behavior. These phenotypes model well the epilepsy (15%), hyperactivity
      (20%) and autism (30%) that are comorbid with FX in human patients. Identifying
      reliable and robust mouse phenotypes to model cognitive impairments is critical
      considering the 90% comorbidity of FX and intellectual disability. Recent work
      characterized a five-choice visuospatial discrimination assay testing cognitive
      flexibility, in which FX model mice show impairments associated with decreases in
      synaptic proteins in prefrontal cortex (PFC). In this study, we sought to
      determine whether instrumental extinction, another process requiring PFC, is
      altered in FX model mice, and whether downregulation of metabotropic glutamate
      receptor signaling pathways is sufficient to correct both visuospatial
      discrimination and extinction phenotypes. We report that instrumental extinction
      is consistently exaggerated in FX model mice. However, neither the extinction
      phenotype nor the visuospatial discrimination phenotype is corrected by
      approaches targeting metabotropic glutamate receptor signaling. This work
      describes a novel behavioral extinction assay to model impaired cognition in
      mouse models of neurodevelopmental disorders, provides evidence that extinction
      is exaggerated in the FX mouse model and suggests possible limitations of
      metabotropic glutamate receptor-based pharmacotherapy. 

PMID- 24684609
TI  - Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron
      delivery and retention at subcellular-scale resolution in human glioblastoma
      cells with imaging secondary ion mass spectrometry (SIMS).
AB  - Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery
      of a sufficient number of boron-10 ((10)B) atoms to individual tumour cells. Cell
      killing results from the (10)B (n, alpha)(7) Li neutron capture and fission
      reactions that occur if a sufficient number of (10)B atoms are localized in the
      tumour cells. Intranuclear (10)B localization enhances the efficiency of cell
      killing via damage to the DNA. The net cellular content of (10)B atoms reflects
      both bound and free pools of boron in individual tumour cells. The assessment of
      these pools, delivered by a boron delivery agent, currently cannot be made at
      subcellular-scale resolution by clinically applicable techniques such as positron
      emission tomography and magnetic resonance imaging. In this study, a secondary
      ion mass spectrometry based imaging instrument, a CAMECA IMS 3f ion microscope,
      capable of 500 nm spatial resolution was employed. Cryogenically prepared
      cultured human T98G glioblastoma cells were evaluated for boron uptake and
      retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has
      been used clinically for BNCT of high-grade gliomas, recurrent tumours of the
      head and neck region and melanomas. The second, a boron analogue of an unnatural
      amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been
      studied in rodent glioma and melanoma models by quantification of boron in the
      nucleus and cytoplasm of individual tumour cells. The bound and free pools of
      boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA
      and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely
      bound form to the nucleus and cytoplasm of human glioblastoma cells. This free
      pool of boron could be easily mobilized out of the cell and was in some sort of
      equilibrium with extracellular boron. In the case of BPA, the intracellular free
      pool of boron also was affected by the presence of phenylalanine in the nutrient
      medium. This suggests that it might be advantageous if patients were placed on a
      low phenylalanine diet prior to the initiation of BNCT. Since BPA currently is
      used clinically for BNCT, our observations may have direct relevance to future
      clinical studies utilizing this agent and provides support for individualized
      treatment planning regimens rather than the use of fixed BPA infusion protocols.

PMID- 24684610
TI  - 'I'm happy that I can still walk'--Participation of the elderly in home care as a
      specific group with specific needs and wishes.
AB  - BACKGROUND: Taking the needs, wishes and experiential knowledge of clients into
      account is considered to result in a better fit between the supply and demand of
      modern health care, contributing to the improvement of individual care,
      organizations, institutions and policy. However, the current generation of the
      elderly have had little experience of consumer-oriented public services. They are
      said to be less likely to discuss their needs and wishes with individual
      caregivers and health-care organisations. As a result, they might not receive
      care matching their needs and wishes. AIM: To examine how the elderly themselves
      refer to their age and their needs and wishes for individual and collective
      participation in home-based care to get a better understanding of their
      participation in their own health care. METHODS: Content analysis of 20 semi
      structured in-depth interviews with elderly recipients of care in the
      Netherlands. RESULTS: The need and ability of the elderly to discuss their
      experiences are strongly affected by physical and mental limitations, social
      cultural characteristics and their experiences of life. As a result, the elderly
      encounter many limitations in discussing their experiences with their individual
      caregivers and their home-care organisation. However, this does not mean that the
      elderly do not have needs and wishes that they want taken into account.
      CONCLUSION: The challenge is to create a more responsive environment and to find
      new, creative ways of facilitating the expression of the needs and wishes of the
      elderly, according to the specific values and norms of their generation.

PMID- 24684612
TI  - How does the heart sense changes in oxygen tension: a role for ion channels?
AB  - SIGNIFICANCE: Oxygen plays a key role in cellular metabolism and function. Oxygen
      delivery to cells is crucial, and a lack of oxygen such as that which occurs
      during myocardial infarction can be lethal. Cells should, therefore, be able to
      respond to changes in oxygen tension. RECENT ADVANCES: Since the first studies
      examining the acute cellular effect of hypoxia on activation of transmitter
      release from glomus or type I chemoreceptor cells, it is now known that virtually
      all cells are able to respond to changes in oxygen tension. CRITICAL ISSUES:
      Despite advances made in characterizing hypoxic responses, the identity of the
      "oxygen sensor" remains debated. Recently, more evidence has evolved as to how
      cardiac myocytes sense acute changes in oxygen. This review will examine the
      available evidence in support of acute oxygen-sensing mechanisms providing a
      brief historical perspective and then more detailed insights into the heart and
      the role of cardiac ion channels in hypoxic responses. FUTURE DIRECTIONS: A
      further understanding of these cellular processes should result in interventions
      that assist in preventing the deleterious effects of acute changes in oxygen
      tension such as alterations in contractile function and cardiac arrhythmia.

PMID- 24684613
TI  - Urinary tract infections during deployment, active component, U.S. Armed Forces,
      2008-2013.
AB  - Austere living conditions during deployment may put service members at greater
      risk for urinary tract infections (UTIs). During the 6-year surveillance period,
      6.5 percent of females (n=7,214) and 0.3 percent of males (n=2,412) who were ever
      deployed had at least one UTI diagnosed while deployed to Southwest Asia and the
      Middle East. The incidence rate of first-time UTIs while deployed was 86.7 per
      1,000 person-years (p-yrs) in females and 3.3 per 1,000 p-yrs in males. Of
      service members with at least one UTI during deployment, 13.6 percent of females
      and 3.6 percent of males had an additional (recurrent) UTI during the same or a
      follow-up deployment period. Among both females and males, rates of UTIs were
      highest among those who were the youngest, in armor/motor transport occupations,
      and "other" (e.g., separated, divorced) marital status. Throughout the
      surveillance period, annual overall rates of UTIs were 26-55 percent higher among
      nondeployed than deployed females and 130-250 percent higher among nondeployed
      than deployed males. Among those diagnosed with UTIs during deployment, 53.6
      percent of females and 13.9 percent of males had at least one UTI diagnosed
      during a medical encounter in a fixed medical treatment facility any time prior
      to deployment. 

PMID- 24684599
TI  - Superoxide dismutases and superoxide reductases.

PMID- 24684614
TI  - Legionellosis in Military Health System beneficiaries, 1998-2013.
AB  - Legionellosis is an infection caused by exposure to mist or vapor contaminated
      with Legionella bacteria. During the 16-year surveillance period, 73 cases of
      legionellosis were identified in active component service members; 37 were
      identified among the reserve component; and 1,044 were identified among all other
      beneficiaries of the Military Health System (MHS). Of the total 1,154 cases of
      legionellosis, 11 percent (n=126) were confirmed cases (i.e., reportable medical
      events); 52 percent (n=599) were probable cases (i.e., hospitalizations); and 37
      percent (n=429) were suspected cases (i.e., ambulatory visits). Most of the cases
      (59%) were identified in individuals aged 60 years and older. The annual number
      of cases increased during the surveillance period and demonstrated a seasonal
      trend with more cases occurring in the summer and early fall. Recent trends in
      the incidence of legionellosis among MHS beneficiaries and civilian populations
      in the United States highlight the importance of correctly identifying the
      etiologic agents of bacterial pneumonia and submitting reports of cases of
      legionellosis through the appropriate reporting system. 

PMID- 24684615
TI  - Update: Heat injuries, active component, U.S. Armed Forces, 2013.
AB  - The number of active component service members treated for heat stroke in 2013
      (n=324) was the lowest since 2010 (n=321). Incidence rates of heat stroke were
      higher among males, those younger than 20 years of age, Asian/Pacific Islanders,
      Marine Corps and Army members, recruit trainees, and service members in combat
      specific occupations, compared to their respective counterparts. Fewer service
      members were treated for "other heat injuries" in 2013 (n=1,701) than in any
      other year of the 5-year surveillance period. In addition, there were fewer
      reportable medical events, ambulatory encounters, and hospitalizations for "other
      heat injuries" in 2013 than in any of the prior 4 years. The incidence rate of
      "other heat injuries" was higher among females than males and 304 percent higher
      among recruit trainees than among other enlisted members or officers. During 2009
      2013, a total of 909 heat injury events occurred in Iraq/Afghanistan; 6.4 percent
      (n=58) of those events were due to heat stroke. 

PMID- 24684616
TI  - Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2009
      2013.
AB  - Among active component U.S. service members in 2013, there were 378 incident
      episodes of rhabdomyolysis likely due to physical exertion or heat stress
      (exertional rhabdomyolysis). The annual incidence rates of exertional
      rhabdomyolysis increased 33 percent during 2009-2013. In 2013, the highest
      incidence rates occurred in service members who were male; younger than 20 years
      of age; either Asian/Pacific Islander or black, non-Hispanic; members of the
      Marine Corps and Army; recruit trainees; and in combat-specific occupations.
      Incidence rates were higher among service members with homes of record from the
      Northeast compared to other regions of the United States. Most cases of
      exertional rhabdomyolysis were diagnosed at installations that support basic
      combat/recruit training or major ground combat units of the Army or Marine Corps.
      Medical care providers should consider exertional rhabdomyolysis in the
      differential diagnosis when service members (particularly recruits) present with
      muscular pain and swelling, limited range of motion, or the excretion of dark
      urine (e.g., myoglobinuria) after strenuous physical activity, particularly in
      hot, humid weather. 

PMID- 24684617
TI  - Update: Exertional hyponatremia, active component, U.S. Armed Forces, 1999-2013.
AB  - From 1999 through 2013, there were 1,406 incident diagnoses of exertional
      hyponatremia among active component members of the U.S. Armed Forces. Annual
      incidence rates rose sharply from 2008 to 2010 but decreased by 59 percent from
      2010 to 2013. In 2013, there were fewer incident cases (n=73) than in any of the
      previous 9 years. The recent decrease in overall rates reflects sharply declining
      rates in the Marine Corps and slight decreases in the other Services. Relative to
      their respective counterparts, crude incidence rates of exertional hyponatremia
      for the entire 15-year surveillance period were higher among females, those in
      the youngest age group, Marines, recruit trainees, and "other" military
      occupations. Service members (particularly recruit trainees) and their
      supervisors must be vigilant for early signs of heat-related illnesses and must
      be knowledgeable of the dangers of excessive water consumption and the prescribed
      limits for water intake during prolonged physical activity (e.g., field training
      exercises, personal fitness training, recreational activities) in hot, humid
      weather. 

PMID- 24684618
TI  - Barriers and enablers to the provision of alcohol treatment among Aboriginal
      Australians: a thematic review of five research projects.
AB  - INTRODUCTION AND AIMS: To review the results of five research projects
      commissioned to enhance alcohol treatment among Aboriginal Australians, and to
      highlight arising from them. DESIGN AND METHODS: Drafts of the papers were
      workshopped by project representatives, final papers reviewed and results
      summarised. Lessons arising were identified and described. RESULTS: While the
      impact of the projects varied, they highlight the feasibility of adapting
      mainstream interventions in Aboriginal Australian contexts. Outcomes include
      greater potential to: screen for those at risk; increase community awareness;
      build capacity and partnerships between organisations; and co-ordinate
      comprehensive referral networks and service provision. DISCUSSION: Results show a
      small investment can produce sustainable change and positive outcomes. However,
      to optimise and maintain investment, cultural difference needs to be recognised
      in both planning and delivery of alcohol interventions; resources and funding
      must be responsive to and realistic about the capacities of organisations;
      partnerships need to be formed voluntarily based on respect, equality and trust;
      and practices and procedures within organisations need to be formalised.
      CONCLUSIONS: There is no simple way to reduce alcohol-related harm in Aboriginal
      communities. However, the papers reviewed show that with Aboriginal control,
      modest investment and respectful collaboration, service enhancements and improved
      outcomes can be achieved. Mainstream interventions need to be adapted to
      Aboriginal settings, not simply transferred. The lessons outlined provide
      important reflections for future research.

PMID- 24684619
TI  - A single molecule perspective on the functional diversity of in vitro evolved
      beta-glucuronidase.
AB  - The mechanisms that drive the evolution of new enzyme activity have been
      investigated by comparing the kinetics of wild-type and in vitro evolved beta
      glucuronidase (GUS) at the single molecule level. Several hundred single GUS
      molecules were separated in large arrays of 62,500 ultrasmall reaction chambers
      etched into the surface of a fused silica slide to observe their individual
      substrate turnover rates in parallel by fluorescence microscopy. Individual GUS
      molecules feature long-lived but divergent activity states, and their mean
      activity is consistent with classic Michaelis-Menten kinetics. The large number
      of single molecule substrate turnover rates is representative of the activity
      distribution within an entire enzyme population. Partially evolved GUS displays a
      much broader activity distribution among individual enzyme molecules than wild
      type GUS. The broader activity distribution indicates a functional division of
      work between individual molecules in a population of partially evolved enzymes
      that-as so-called generalists-are characterized by their promiscuous activity
      with many different substrates.

PMID- 24684620
TI  - IFNgamma and perforin cooperate to control infection and prevent fatal pathology
      during persistent gammaherpesvirus infection in mice.
AB  - Infection with murine gammaherpesvirus 68 has become an accepted model for
      studying the virus/host interactions with regard to gammaherpesvirus infections.
      Previous studies using gene-deficient mice have revealed that neither IFNgamma
      nor perforin is essential in controlling the outcome of infection or the virus
      load during chronic infection in C57BL/6 mice. However, pronounced multiorgan
      fibrosis and splenic atrophy are observed in mice lacking IFNgamma or the
      IFNgamma receptor. To study the interplay between perforin and IFNgamma in
      controlling the virus-induced pathology and the viral load during chronic
      gammaherpesvirus infection, we infected IFNgamma/perforin double-deficient
      C57BL/6 mice and followed the course of infection. While absence of perforin
      prevented the splenic atrophy in IFNgamma-deficient mice, fibrosis did not
      disappear. Moreover, double-deficient mice developed extreme splenomegaly, were
      unable to control the viral load and displayed chronic immune activation. Thus,
      IFNgamma and perforin act in concert to minimize pathology and control the viral
      load in mice chronically infected with MHV68. Furthermore, while certain aspect
      of the virus-induced pathology in IFNgamma-deficient mice may be alleviated in
      double-deficient mice, other aspects are exaggerated, and the normal architecture
      of the spleen is completely destroyed. We believe that these findings add to the
      understanding of the virus/host interaction during chronic gammaherpes virus
      infection.

PMID- 24684621
TI  - Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy
      greyhound dogs.
AB  - The purpose of this study was to compare the pharmacokinetics of two highly
      protein-bound, lipophilic opioid drugs. Fentanyl (10 MUg/kg) and buprenorphine
      (20 MUg/kg) were administered intravenously (IV) to six healthy greyhound dogs
      (three males and three females). The doses were based on clinically administered
      doses for dogs. Plasma drug concentrations were determined using liquid
      chromatography with mass spectrometry, and noncompartmental pharmacokinetics were
      estimated with computer software. The volume of distribution (area) was larger
      for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma
      clearance of fentanyl (38.6 mL.min/kg) was faster than buprenorphine (10.3
      mL.min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than
      buprenorphine (3.96 h). Despite similar physicochemical properties including
      octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and
      buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%)
      are considered highly protein bound, but the differences in protein binding may
      contribute to the lack of similarity of pharmacokinetics in healthy dogs. 

PMID- 24684622
TI  - Microrheology and microstructure of Fmoc-derivative hydrogels.
AB  - The viscoelasticity of hydrogel networks formed from the low-molecular-weight
      hydrogelator Fmoc-tyrosine (Fmoc-Y) is probed using particle-tracking
      microrheology. Gelation is initiated by adding glucono-delta-lactone (GdL), which
      gradually lowers the pH with time, allowing the dynamic properties of gelation to
      be examined. Consecutive plots of probe particle mean square displacement (MSD)
      versus lag time tau are shown to be superimposable, demonstrating the formation
      of a self-similar hydrogel network through a percolation transition. The analysis
      of this superposition yields a gel time t(gel) = 43.4 +/- 0.05 min and a critical
      relaxation exponent n(c) = 0.782 +/- 0.007, which is close to the predicted value
      of 3/4 for semiflexible polymer networks. The generalized Stokes-Einstein
      relation is applied to the master curves to find the viscoelastic moduli of the
      critical gel over a wide frequency range, showing that the critical gel is
      structurally and rheologically fragile. The scaling of G'/G" as omega(0.795+/
      0.099) ~ omega(3/4) at high frequencies provides further evidence for
      semiflexible behavior. Cryogenic scanning electron micrographs depict a loosely
      connected network close to the gel point with a fibrillar persistence length that
      is longer than the network mesh size, further indications of semiflexible
      behavior. The system reported here is one of a number of synthetic systems shown
      to exhibit semiflexible behavior and indicates the opportunity for further
      rheological study of other Fmoc derivatives.

PMID- 24684623
TI  - Mycobacterium tuberculosis serine protease Rv3668c can manipulate the host
      pathogen interaction via Erk-NF-kappaB axis-mediated cytokine differential
      expression.
AB  - Tuberculosis caused by Mycobacterium tuberculosis (MTB) remains a serious global
      public health concern. About one-third of the global population has been latently
      infected with this pathogen. MTB proteases are important virulence factors and
      involve in subverting the host immunity. MTB protease Rv3668c was implicated in
      drug action and dormancy by Gene Expression Omnibus data. To define the role of
      Rv3668c in pathogen-host interaction, we constructed recombinant strain
      Mycobacterium smegmatis-Rv3668c (Ms-Rv3668c). The resultant strains were used to
      challenge the human macrophage cell line U937. The cytokine levels and the
      survival of recombinants and macrophages were monitored. The results showed that
      recombinant Ms-Rv3668c specifically upregulated the secretion of proinflammatory
      cytokines TNF-alpha, IL-1beta, and IL-6 and downregulated the secretion of anti
      inflammatory cytokine IL-10 by U937 cells, consistent with the upregulated
      transcription of TNF-alpha and IL-1beta. Rv3668c recombinants demonstrated
      prolonged survival within the U937 cells and accelerated the death of the host
      cells. Inhibitor experiments showed that the ERK-NF-kappaB axis was involved in
      the Rv3668c-triggered TNF-alpha and IL-1beta changes. These results provided
      evidence for the engagement of Rv3668c in the interaction between Mycobacterium
      and host. 

PMID- 24684624
TI  - First report of genotyping of Toxoplasma gondii in free-living Microtus fortis in
      northeastern China.
AB  - Toxoplasma gondii is an intracellular protozoan parasite which imperils the
      health of almost all warm-blooded animals, including humans. The objective of
      this study was to determine genetic characterization of T. gondii in free-living
      Microtus fortis (reed vole) in Jilin province, northeastern China. A total of 104
      DNA samples, 74 from Gongzhuling and 30 from Baicheng, were extracted from lung
      tissues of M. fortis , and 56 (53.8%) of them were positive for T. gondii by semi
      nested polymerase chain reaction of the B1 gene. These positive DNA samples were
      typed at 10 genetic markers including SAG1, 5'- and 3'-SAG2, alternative SAG2,
      BUTB, GRA6, L358, PK1, c22-8, c29-2, and Apico. Four samples were successfully
      genotyped at all genetic loci and grouped to 2 distinct genotypes; 2 samples
      belonged to ToxoDB Genotype no. 10 (Type I) and the other 2 presented ToxoDB
      Genotype no. 9 ( http://toxodb.org/toxo/ ); 4 samples were genotyped at 8 genetic
      loci, in which 2 samples belonged to ToxoDB Genotype no. 10 and 2 presented
      ToxoDB Genotype no. 9. To our knowledge, this is the first report of genetic
      typing of T. gondii from free-living M. fortis in northeast China. The results
      suggest that the Type I and ToxoDB Genotype no. 9 could be a potential risk
      factor for transmission through the reed vole in this region. 

PMID- 24684626
TI  - Identification and functional characterization of novel genetic variations in
      porcine TLR5 promoter.
AB  - Toll-like receptors (TLRs) play a critical role in the immune process acting as
      innate sensors of pathogens. Toll-like receptor 5 (TLR5) is especially relevant
      in those tissues maintaining close contact with microorganisms, not only because
      it prevents infections but also due to its involvement in the regulation of host
      commensal interactions. Recent studies suggest that the occurrence of genetic
      polymorphisms may impair TLR function, consequently increasing or decreasing the
      individual susceptibility to infectious diseases. In this study, the promoter
      sequence of the porcine TLR5 gene was scanned with the aim of identifying
      mutations with potential effects on gene expression. Two Indel variations in the
      predicted promoter sequence and seven single-nucleotide polymorphisms were
      identified. The luciferase reporter gene assay indicated that one Indel,
      consisting in a 23-bp insertion at the -581 to -559 nucleotide position, creates
      an additional STAT binding site, and it is associated with an increase of the
      promoter activity. This finding suggests that genetic variation in the TLR5
      promoter could alter the expression of the gene, and may be used as a molecular
      marker to define pathogen susceptibility or resistance patterns in pigs.

PMID- 24684627
TI  - Prognostic value of clinical and immunological markers in acute phase of SFTS
      virus infection.
AB  - SFTS virus (SFTSV) is a novel bunyavirus that causes severe fever with
      thrombocytopenia syndrome (SFTS), an emerging infectious disease that occurred in
      China in recent years, with an average case fatality rate of 10-12%. Intervention
      in the early clinical stage is the most effective measure to reduce the mortality
      rate of disease. To elucidate the natural course of and immune mechanisms
      associated with the pathogenesis of SFTSV, 59 laboratory-confirmed SFTS patients
      in the acute phase, who were hospitalized between October 2010 and September
      2011, were enrolled in this study, and the patients sera were dynamically
      collected and tested for SFTSV viral RNA load, 34 cytokines or chemokines and
      other related laboratory parameters. All clinical diagnostic factors in the acute
      phase of SFTS were evaluated and assessed. The study showed that the severity of
      the disease in 11 (18.6%) patients was associated with abdominal pain (p 0.007;
      OR = 21.95; 95% CI, 2.32-208.11) and gingival bleeding (p 0.001; OR=122.11; 95%
      CI, 6.41-2328). The IP-10, TNF-alpha, IL-6, IL-10, granzyme B and HSP70 levels
      were higher over the 7-8 days in severe cases, accompanied by altered AST, CK and
      LDH levels. HSP70 (p 0.012; OR=8.29; 95% CI, 1.58-43.40) was independently
      correlated with the severity of the early acute phase of SFTSV infection. The
      severity of SFTS can be predicted based on the presence of symptoms such as
      abdominal pain and gingival bleeding and on the level of HSP70 in the acute phase
      of the disease.

PMID- 24684628
TI  - The 5' promoter region of MHC class I chain-related gene B.
AB  - In this study, the 5' promoter region of MHC class I chain-related gene B (MICB)
      was investigated in 104 healthy, unrelated Han individuals recruited from
      northern China, using polymerase chain reaction (PCR)-sequencing methodology.
      Fifteen variable sites were detected, which showed a mosaic pattern of
      significant global linkage disequilibrium (LD). Eleven different 5' promoter
      haplotypes were identified. MICB 5' promoter haplotype-9 carrying CT deletion at
      positions -139/-138, which is associated with decreased MICB promoter activity,
      was present in 26.9% of MICB alleles and was linked to MICB*002:01, MICB*008, and
      MICB*014 in this population. In addition, rs3828913 (position -176) and rs3828914
      (position -152) were located adjacent to HSRE and GC box in MICB promoter,
      respectively. Sixteen extended haplotypes (EH) incorporating the MICB 5' promoter
      and MICB coding region were observed in this population, eight of which were in
      significant LD. Phylogenetic analysis of 5' promoter refined MICB sub-lineage
      structure indicated that MICB*005:02, the most common MICB allele, consists of
      five sub-lineages. Ewens-Watterson homozygosity statistics at MICB 5' promoter
      region were consistent with neutral expectations. Our study has shed new insight
      into MICB genetic variation at population level, suggesting that binding sites
      for transcription factors in MICB promoter could be interrupted by polymorphisms
      within this region, resulting in allele-specific regulation. The data will
      facilitate the understanding of regulation of MICB gene transcription, and will
      inform studies of evolution of the major histocompatibility complex (MHC) gene
      complex. 

PMID- 24684629
TI  - Is there a problem with the status quo? Debating the need for standalone ethical
      guidelines for research with people who use alcohol and other drugs.
AB  - In 2011, the Australian National Health and Medical Research Council (NHMRC)
      initiated an inquiry to determine whether there is a need for expanded ethical
      guidance in the form of a discrete guidance document for alcohol and other drug
      (AOD) research. An issues paper was developed to frame the inquiry. AOD
      researchers, Human Research Ethics Committees and others were invited to discuss
      whether there are distinctive ethical issues facing researchers and Human
      Research Ethics Committees in the AOD setting. Based on the public submissions,
      the NHMRC recommended that no AOD research-specific guidance is required. The
      inquiry and the NHMRC decision were not widely publicized, and we feel there is a
      need for further discussion. In order to do so, we have analysed the public
      inquiry submissions and described the central themes. Few submissions in the
      inquiry explicitly agreed AOD research warrants a specific guidance framework.
      Most were concerned that the NHMRC issues paper unfairly targeted people who use
      drugs as complex research participants. The inquiry highlights tensions around
      research governance and ethics review boards dealing with illicit and stigmatised
      behaviours. While we agree that a specific guidance framework for AOD research is
      not needed and could potentially be harmful and restrictive, we are concerned
      that the wholesale rejection of a guidance framework has closed the door to much
      needed debate. There remains, we argue, a need for alternative strategies and
      tools to support ethical research, inform and streamline institutional ethics
      approval, and engage and protect participants.

PMID- 24684625
TI  - Biochemistry and theory of proton-coupled electron transfer.

PMID- 24684630
TI  - Impairments of long-term depression induction and motor coordination precede
      Abeta accumulation in the cerebellum of APPswe/PS1dE9 double transgenic mice.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that represents the most
      common type of dementia among elderly people. Amyloid beta (Abeta) peptides in
      extracellular Abeta plaques, produced from the amyloid precursor protein (APP)
      via sequential processing by beta- and gamma-secretases, impair hippocampal
      synaptic plasticity, and cause cognitive dysfunction in AD patients. Here, we
      report that Abeta peptides also impair another form of synaptic plasticity;
      cerebellar long-term depression (LTD). In the cerebellum of commonly used AD
      mouse model, APPswe/PS1dE9 mice, Abeta plaques were detected from 8 months and
      profound accumulation of Abeta plaques was observed at 18 onths of age.
      Biochemical analysis revealed relatively high levels of APP protein and Abeta in
      the cerebellum of APPswe/PS1dE9 mice. At pre-Abeta accumulation stage, LTD
      induction, and motor coordination are disturbed. These results indicate that
      soluble Abeta oligomers disturb LTD induction and cerebellar function in AD mouse
      model.

PMID- 24684631
TI  - Evaluating newly acquired authority of nurse practitioners and physician
      assistants for reserved medical procedures in the Netherlands: a study protocol.
AB  - AIM: The study protocol is designed to evaluate the effects of granting
      independent authorization for medical procedures to nurse practitioners and
      physician assistants on processes and outcomes of health care. BACKGROUND: Recent
      (temporarily) enacted legislation in Dutch health care authorizes nurse
      practitioners and physician assistants to indicate and perform specified medical
      procedures, i.e. catheterization, cardioversion, defibrillation, endoscopy,
      injection, puncture, prescribing and simple surgical procedures, independently.
      Formerly, these procedures were exclusively reserved to physicians, dentists and
      midwives. DESIGN: A triangulation mixed method design is used to collect
      quantitative (surveys) and qualitative (interviews) data. METHODS: Outcomes are
      selected from evidence-based frameworks and models for assessing the impact of
      advanced nursing on quality of health care. Data are collected in various
      manners. Surveys are structured around the domains: (i) quality of care; (ii)
      costs; (iii) healthcare resource use; and (iv) patient centredness. Focus group
      and expert interviews aim to ascertain facilitators and barriers to the
      implementation process. Data are collected before the amendment of the law, 1 and
      2.5 years thereafter. Groups of patients, nurse practitioners, physician
      assistants, supervising physicians and policy makers all participate in this
      national study. The study is supported by a grant from the Dutch Ministry of
      Health, Welfare and Sport in March 2011. Research Ethics Committee approval was
      obtained in July 2011. CONCLUSION: This study will provide information about the
      effects of granting independent authorization for medical procedures to nurse
      practitioners and physician assistants on processes and outcomes of health care.
      Study findings aim to support policy makers and other stakeholders in making
      related decisions. The study design enables a cross-national comparative
      analysis.

PMID- 24684632
TI  - Salicylic acid prevents Trichoderma harzianum from entering the vascular system
      of roots.
AB  - Trichoderma is a soil-borne fungal genus that includes species with a significant
      impact on agriculture and industrial processes. Some Trichoderma strains exert
      beneficial effects in plants through root colonization, although little is known
      about how this interaction takes place. To better understand this process, the
      root colonization of wild-type Arabidopsis and the salicylic acid (SA)-impaired
      mutant sid2 by a green fluorescent protein (GFP)-marked Trichoderma harzianum
      strain was followed under confocal microscopy. Trichoderma harzianum GFP22 was
      able to penetrate the vascular tissue of the sid2 mutant because of the absence
      of callose deposition in the cell wall of root cells. In addition, a higher
      colonization of sid2 roots by GFP22 compared with that in Arabidopsis wild-type
      roots was detected by real-time polymerase chain reaction. These results,
      together with differences in the expression levels of plant defence genes in the
      roots of both interactions, support a key role for SA in Trichoderma early root
      colonization stages. We observed that, without the support of SA, plants were
      unable to prevent the arrival of the fungus in the vascular system and its spread
      into aerial parts, leading to later collapse. 

PMID- 24684634
TI  - The real end of ageism.

PMID- 24684633
TI  - [2,3]-Sigmatropic rearrangement of allylic selenimides: strategy for the
      synthesis of peptides, peptidomimetics, and N-aryl vinyl glycines.
AB  - The scope of the NCS-mediated amination/[2,3]-sigmatropic rearrangement of
      enantioenriched allylic selenides has been expanded to provide access to three
      new product classes. The use of N-protected amino acid amides provides a novel
      strategy for accessing peptide chains containing unnatural vinyl glycine amino
      acid residues. Also reported is the use of amino acid esters, allowing the
      diastereoselective synthesis of N,N-dicarboxymethylamines, a motif found in a
      number of pharmaceuticals. Furthermore, use of a range of N-aromatic and N
      heteroaromatic amines allows the formation of enantioenriched N-arylamino acids,
      a motif found in a number of synthetically and biologically interesting
      compounds. 

PMID- 24684635
TI  - Preharvest application of oxalic acid increased fruit size, bioactive compounds,
      and antioxidant capacity in sweet cherry cultivars (Prunus avium L.).
AB  - Trees of 'Sweet Heart' and 'Sweet Late' sweet cherry cultivars (Prunus avium L.)
      were treated with oxalic acid (OA) at 0.5, 1.0, and 2.0 mM at 98, 112, and 126
      days after full blossom. Results showed that all treatments increased fruit size
      at harvest, manifested by higher fruit volume and weight in cherries from treated
      trees than from controls, the higher effect being found with 2.0 mM OA (18 and
      30% higher weight for 'Sweet Heart' and 'Sweet Late', respectively). Other
      quality parameters, such as color and firmness, were also increased by OA
      treatments, although no significant differences were found in total soluble
      solids or total acidity, showing that OA treatments did not affect the on-tree
      ripening process of sweet cherry. However, the increases in total anthocyanins,
      total phenolics, and antioxidant activity associated with the ripening process
      were higher in treated than in control cherries, leading to fruit with high
      bioactive compounds and antioxidant potential at commercial harvest (?45% more
      anthocyanins and ?20% more total phenolics). In addition, individual
      anthocyanins, flavonols, and chlorogenic acid derivatives were also increased by
      OA treatment. Thus, OA preharvest treatments could be an efficient and natural
      way to increase the quality and functional properties of sweet cherries. 

PMID- 24684636
TI  - Computational two-dimensional infrared spectroscopy without maps: N
      methylacetamide in water.
AB  - The two-dimensional infrared spectrum of NMAH and NMAD in H2O and D2O is computed
      on the basis of force field parametrizations ranging from standard point charge
      (PC) to more elaborate multipolar (MTP) representations of the electrostatics.
      For the latter, the nonbonded parameters (MTP and van der Waals) were optimized
      to reproduce thermodynamic data. The frequency trajectory and frequency-frequency
      correlation function (FFCF) are determined from explicit frequency calculations
      on ~10(6) snapshots without using a more traditional "mapping" approach. This
      allows us to both sample configurations and compute observables in a consistent
      fashion. In agreement with experiment, the FFCF shows one very rapid time scale
      (in the 50 fs range) followed by one or two longer time scales. In the case of
      three time scales, the intermediate one is ~0.5 ps or shorter, whereas the
      longest time scale can extend up to 2 or 3 ps. All interaction models lead to
      three time scales in the FFCF when fitted to an empirical parametrized form. When
      two time scales are assumed-as is usually done in the analysis of experimental
      data-and the short time scale is fixed to the tau1 = 50-100 fs range, the
      correlation time tauc from the simulations ranges from 0.7 to 1 ps, which agrees
      quite well with experimentally determined values. The major difference between
      MTP and PC models is the observation that the later decay times in the FFCF are
      longer for simulations with MTPs. Also, the amplitude of the FFCF is reduced when
      simulations are carried out with MTPs. Overall, however, PC-based models perform
      well compared to those based on MTPs for NMAD in D2O and can be recommended for
      such investigations in the context of peptide and protein simulations. 

PMID- 24684637
TI  - An ethical framework for pharmacy management: balancing autonomy and other
      principles.
AB  - Decisions to control pharmaceutical costs can cause conflicts as to what
      medications are covered. Such conflicts have ethical implications, however
      implicit, and given this fact, an ethical framework can help address them. In the
      following commentary, we discuss the more traditional, individual-level ethical
      considerations likely familiar to most clinicians. We, then, discuss population
      level ethical constructs that clinicians may not as readily embrace. We also
      present a hypothetical cancer-care case to illustrate how imbalances in ethical
      foci between individual- and population-level constructs may lead to conflicts
      among health care actors and promote shifts in pharmaceutical decision making
      away from providers and toward payers, paradoxically reducing provider autonomy
      and hence patient autonomy. Finally, we propose a more comprehensive ethical
      framework to help converge individual, payer, and societal interests when making
      pharmaceutical use decisions. Pharmacists play a crucial role as pharmacy
      benefits managers and should be familiar with individual- and population-based
      ethical constructs. 

PMID- 24684639
TI  - Current and future roles of targeted therapy and immunotherapy in advanced
      melanoma.
AB  - BACKGROUND: Melanoma is an aggressive disease that accounts for approximately 75%
      of skin cancer-related deaths. Historically, treatment options for patients with
      advanced stage melanoma have been limited by modest response rates and failure to
      improve overall survival. The treatment landscape for advanced stage melanoma was
      revolutionized in 2011 with the approval of ipilimumab and vemurafenib, both of
      which improved overall survival in phase III clinical trials. More recently, the
      targeted inhibitors dabrafenib and trametinib have demonstrated similar
      therapeutic profiles. OBJECTIVES: To (a) discuss emerging treatment options for
      advanced melanoma, specifically ilpilimumab, vemurafenib, dabrafenib, and
      trametinib, in the context of their mechanisms of action and their potential for
      long-term improvement in patient outcome, and (b) to consider the impact of these
      agents on the current treatment landscape. METHODS: A literature search was
      conducted to collect data from clinical trials involving ipilimumab, vemurafenib,
      dabrafenib, and trametinib. Emphasis was placed on outcome measures related to
      long-term clinical benefit. RESULTS: Ipilimumab, a fully human monoclonal
      antibody, exploits the natural ability of the immune system to eradicate primary
      cancer cells. It inhibits the binding of cytotoxic T-lymphocyte antigen-4 to its
      ligands, thereby potentiating T-cell response and antitumor immunity. In a phase
      III clinical trial, ipilimumab at 3 mg/kg improved overall survival in previously
      treated patients with metastatic melanoma. Components of the mitogen-activated
      protein kinase (MAPK) pathway are particularly relevant in melanoma and have been
      targeted by small molecular inhibitors. Vemurafenib and dabrafenib inhibit the
      BRAF V600 mutation, which prevents oncogenic activities such as uncheck
      proliferation and evasion of immune response. Data from phase III clinical trials
      suggest that both vemurafenib and dabrafenib improve patient outcomes, with
      vemurafenib showing an overall survival benefit and dabrafenib showing improved
      median progression-free survival. The targeted-therapy approach in melanoma
      continued to gain momentum with the development of trametinib, which inhibits the
      MEK protein, the only known substrate of the BRAF V600 protein. Inhibition of MEK
      leads to decreased cell signaling and proliferation in cancer cells. In phase III
      trials, trametinib demonstrated significant improvement in median progression
      free survival and median overall survival compared with chemotherapy treatment,
      making this treatment a valuable addition to the current armamentarium. The
      adverse events associated with these new treatments are generally tolerable and
      mild to moderate in severity; however, care should be taken when selecting a
      therapy, since the specific adverse events associated with these treatments are
      unique, and serious events have been reported. CONCLUSIONS: The immunotherapy
      ipilimumab and the MAPK-targeted inhibitors vemurafenib, dabrafenib, and
      trametinib have forever changed the treatment landscape for melanoma. Indeed,
      these new therapies have demonstrated long-term improvement in patient outcome, a
      benefit not afforded by traditional therapeutics. Important research continues on
      the molecular basis of melanoma, and new targets are likely to emerge. Other
      areas of work include optimization of sequencing and/or combination of current
      treatments, which may increase the number of patients who experience clinical
      benefit.

PMID- 24684638
TI  - Missed opportunities for HIV screening in pharmacies and retail clinics.
AB  - In the wake of new recommendations to offer HIV screening to everyone aged 13-64
      years and to start all people living with HIV/AIDS on highly active
      antiretroviral therapy (HAART) regardless of CD4 count, the need to generate
      widespread, scalable HIV screening programs is greater than ever. Nearly 50,000
      new HIV infections occur in the United States each year, and the Centers for
      Disease Control and Prevention estimates that approximately half of these new
      infections are transmitted by individuals who are unaware of their HIV
      serostatus. Numerous barriers to screening exist, including the lack of primary
      care for many at-risk patients, expense of screening in traditional settings, and
      need for repeat testing in high-risk populations. With their relative
      accessibility and affordability, community pharmacies and retail clinics within
      those pharmacies are practical and appealing venues for expanded HIV screening.
      For widespread pharmacy-based testing to become a reality, policymakers and
      corporate pharmacy leadership would need to develop innovative solutions to the
      existing time pressures of pharmacists' behind-the-counter functions and absence
      of reimbursement for direct patient care services. Pharmacists nationwide should
      also receive training to assist with risk reduction counseling and linkage to
      care for customers purchasing the new over-the-counter HIV test.

PMID- 24684640
TI  - Descriptive review and analysis of immunoglobulin utilization management from
      2,548 prior authorization requests.
AB  - BACKGROUND: Immunoglobulin (Ig) is a costly blood product prescribed as immune
      replacement or modulation therapy to treat a wide spectrum of medical conditions.
      While the FDA has approved Ig for a limited number of indications, there are
      multiple off-label uses that have demonstrated proven clinical benefit or are
      currently in various phases of clinical study. There are also diagnoses for which
      Ig is prescribed, but for which no evidence-based efficacy data are available.
      Many conditions for which Ig has been prescribed are extremely rare, and a
      controlled clinical trial is not logistically possible. These conditions may be
      denied insurance authorization because of limited medical evidence that supports
      the use of Ig in their treatment. This limited evidence consists of uncontrolled
      studies, case series and reports, and expert opinion. Limiting the use of Ig
      therapy to cases with the best supporting evidence may control health care
      expenditure, but it may also limit the potential body of knowledge from
      publications by physicians with experience in treating these conditions.
      Specialty pharmacy providers can collect longitudinal outcomes, and data from
      their publications could provide support for improved managed care criteria or
      areas of future medical research. OBJECTIVES: To (a) assess levels of supporting
      evidence by diagnosis for a sample of Ig requests submitted through the managed
      care prior authorization (PA) process and (b) provide a descriptive review of
      such requests and resultant benefit coverage determinations by individual
      diagnosis, overarching diagnostic category, patient age group, and assessed
      levels of evidence. METHODS: Through collaboration with 6 health plans, we
      obtained and analyzed 2,548 managed care PA requests for Ig therapy received
      between February 2008 and August 2012, as well as resulting benefit coverage
      determinations. A literature review of 7 established treatment guidelines and
      expert consensus statements was conducted and used to evaluate all indications
      for Ig treatment presented among obtained requests and to assign each request to
      1 of 5 categorical levels of supporting evidence. RESULTS: Of the 2,548 Ig
      requests reviewed, 1,467 (57.6%) were found to be "supported" in the relevant
      literature; 830 (32.6%) were designated "conditional"; 127 (5%) were "lacking
      consensus"; 74 (2.9%) were "currently not supported"; and 50 (2%) were
      "undetermined." Overall, 2,094 (82.2%) of the requests were authorized by the
      health plans. Of the total requests, 1,633 (64.1%) were for FDA-approved
      diagnostic indications, of which 1,393 (85.3%) were authorized by the sampled
      health plans. The majority of requests for Ig were for treatment of neurological
      and immunological conditions. A total of 181 unique indications were identified,
      yet 833 (32.7%) of the requests were for just 2 indications-common variable
      immunodeficiency and chronic inflammatory demyelinating polyneuropathy. Patients
      aged 45 to 64 years represented 1,318 (51.7%) of all requests. CONCLUSIONS: This
      analysis provides insight into the prescribed medical usage of Ig and the
      conditions for which it may be authorized through the managed care PA process. We
      identified 181 unique diagnostic indications for Ig, for which only 97 had
      established expert consensus. Although many diagnostic indications were
      identified, most requests were for indications with strong supporting evidence,
      and most of these were authorized by the health plans. The number of indications
      identified highlights the ongoing need for publications from physicians and
      specialty pharmacies with experience in treating these conditions in order to
      increase the body of knowledge surrounding use of this therapy.

PMID- 24684641
TI  - Health care resource utilization following initiation of a triptan: a
      retrospective claims analysis.
AB  - BACKGROUND: 23 million Americans suffer from migraine headaches, incurring more
      than $1 billion in direct medical costs each year (with another $13 billion in
      indirect productivity losses). Triptans are the most common treatment of choice
      for these patients; however, adherence and persistence to triptans are poor.
      Partly due to poor adherence to therapy, the ability of triptans to reduce the
      utilization of other medical services and prescription drugs remains unclear.
      OBJECTIVES: To (a) assess changes in the utilization of medical services and
      relevant prescription drugs after patients suffering from episodic migraines
      begin triptan therapy and (b) further investigate the relationship between
      concomitant opioid use among triptan-treated migraine patients and further
      utilization of medical services and prescription drugs. METHODS: A retrospective
      analysis of pharmacy and medical insurance claims was carried out using a large
      and nationally representative database. The utilization patterns of episodic
      migraine patients were observed for 12 to 24 months prior to their first triptan
      prescription and 12 to 24 months following that prescription. Resource
      utilization included physician office visits, diagnostic imaging, emergency room
      use, inpatient hospitalization, opioid prescriptions, migraine prophylaxis
      prescriptions, and acetaminophen or nonsteroidal anti-inflammatory prescriptions.
      Results were stratified according to triptan-switching behavior. RESULTS: The
      analytic sample included 9,521 migraine patients who were followed for a median
      of 550 days before and after their first triptan fill. 40.9% of these patients
      filled their triptan prescriptions only once (index fill). Another 40.3% filled a
      triptan prescription at least twice and never switched their triptan brand. 15.6%
      of patients switched their triptan prescriptions once, and 3.2% of patients
      switched their triptan prescriptions twice or more. The only group to display
      significant reductions in resource utilization following the prescription of a
      triptan was the cohort that never refilled the medication, potentially suggestive
      of misdiagnosis. Either no significant change or a significant increase in
      resource utilization was seen in all other cases. The ability of triptans to
      reduce resource utilization seemed to be lower among patients who switched
      triptans more often. Patients that concomitantly used opioid medications in
      addition to triptans also used significantly more resources than migraine
      patients who were not treated with opioids. CONCLUSION: Contrary to the findings
      of some previous research, the initiation of triptan therapy did not
      significantly reduce the utilization of migraine-related medical services or
      other relevant prescription drugs in this retrospective claims analysis. This may
      have been due to higher and more realistic rates of triptan switching and
      discontinuation. Consistent with previous findings, patients using concomitant
      opioids used more migraine-related health care resources.

PMID- 24684642
TI  - Simultaneous use of amiodarone influences warfarin maintenance dose but is not
      associated with adverse events.
AB  - BACKGROUND: Drug interaction studies selecting patients in a real-life setting
      are scarce, and most studies to date are characterized by a small sample size.
      OBJECTIVE: To evaluate the effect of amiodarone on warfarin maintenance dose and
      adverse events in an anticoagulation cohort from a tertiary cardiovascular
      service. METHODS: This study recruited 866 patients, and oral anticoagulant
      therapy was monitored by the prothrombin time expressed as the international
      normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673
      polymorphisms was performed. RESULTS: Of the 866 patients, 111 (12.8%) were
      taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the
      therapeutic target dose. The warfarin maintenance dose was significantly lower in
      patients simultaneously using amiodarone (23.8 +/- 11.3 mg/wk) compared with
      other patients (29.5 +/- 14.3 mg/wk; P < 0.001). Patients taking amiodarone had
      higher INR/current dose ratios (0.83 +/- 0.04 per mg) compared with patients not
      using amiodarone (0.71 +/- 0.02 per mg, P = 0.001). Adverse event frequency was
      not different between the groups (P = 0.40). No genotype effect was noted on the
      odds of bleeding associated with amiodarone use. CONCLUSIONS: Simultaneous use of
      amiodarone influences warfarin maintenance dose, but is not associated with
      adverse events.

PMID- 24684643
TI  - Economic burden of irritable bowel syndrome with constipation: a retrospective
      analysis of health care costs in a commercially insured population.
AB  - BACKGROUND: The prevalence of irritable bowel syndrome with constipation (IBS-C)
      is estimated to be between 4.3% and 5.2% among adults in the United States.
      Little is known about the health care resource utilization and costs associated
      with IBS-C. OBJECTIVES: To (a) evaluate the annual total all-cause,
      gastrointestinal (GI)-related, and IBS-C-related health care costs among IBS-C
      patients seeking medical care in a commercially insured population and (b)
      estimate the incremental all-cause health care costs among IBS-C patients
      relative to matched controls. METHODS: Patients aged >= 18 years with continuous
      medical and pharmacy benefit eligibility in 2010 were identified from the
      HealthCore Integrated Research Database, which consists of administrative claims
      from 14 geographically dispersed U.S. health plans representing 45 million lives.
      IBS-C patients were defined as those with >= 1 medical claim with an ICD-9-CM
      diagnosis code in any position for IBS (ICD-9-CM 564.1x) and either >= 2 medical
      claims for constipation (ICD-9-CM 564.0x) on different service dates or >= 1
      medical claim for constipation plus >= 1 pharmacy claim for a constipation
      related prescription on different dates of service during the study period.
      Controls were defined as patients without any medical claims for IBS,
      constipation, abdominal pain, or bloating or pharmacy claims for constipation
      related prescriptions. Controls were randomly selected and matched with IBS-C
      patients in a 1:1 ratio based on age (+/- 4 years), gender, health plan region,
      and health plan type. Patients with diagnoses or prescriptions suggesting mixed
      IBS, IBS with diarrhea, chronic diarrhea, or drug-induced constipation were
      excluded. Total health care costs in 2010 U.S. dollars were defined as the sum of
      health plan and patient paid costs for prescriptions and medical services,
      including inpatient visits, emergency room (ER) visits, physician office visits,
      and other outpatient services. The total cost approach was used to assess total
      all-cause or disease-specific health care costs for patients with IBS-C, while
      the incremental cost approach was used to examine the excess all-cause costs of
      IBS-C by comparing IBS-C patients with matched controls. Generalized linear
      models with bootstrapping were used to assess the incremental all-cause costs
      attributable solely to IBS-C after adjusting for demographics, Elixhauser
      Comorbidity Index (ECI) score, and other general and GI-related comorbidities not
      included in the ECI score. RESULTS: A total of 7,652 patients (n = 3,826 each in
      the IBS-C and control cohorts) were included in the analysis. The mean (+/- SD)
      age was 48 (+/- 17) years, and 83.6% were female. The mean annual all-cause
      health care costs for IBS-C patients were $11,182, with over half (53.7%) of the
      costs attributable to outpatient services, including physician office visits and
      other outpatient services (13.1% and 40.6%, respectively). Remaining total all
      cause costs were attributable to hospitalizations (21.8%), prescriptions (19.1%),
      and ER visits (5.4%). GI-related costs ($4,456) comprised 39.8% of total all
      cause costs, while IBS-C-related costs ($1,335) accounted for 11.9% and were
      primarily driven by costs of other outpatient services (50.3%). After adjusting
      for demographics and comorbidities, the incremental annual all-cause health care
      costs associated with IBS-C were $3,856 ($8,621 for IBS-C patients vs. $4,765 for
      controls, P less than 0.01) per patient per year, of which 78.1% of the
      incremental costs were due to medical services, and 21.9% were due to
      prescription fills. CONCLUSIONS: IBS-C imposes a substantial economic burden in
      terms of direct health care costs in a commercially insured population. Compared
      with matched controls, IBS-C patients incurred significantly higher total annual
      all-cause health care costs even after controlling for general and GI-related
      comorbidities. Incremental all-cause costs associated with IBS-C were mainly
      driven by costs related to more frequent use of medical services as opposed to
      prescriptions.

PMID- 24684644
TI  - Health care burden of dyspepsia among nonvalvular atrial fibrillation patients.
AB  - BACKGROUND: Although dyspepsia is common among nonvalvular atrial fibrillation
      (NVAF) patients, its impact on patient health and cost has not been adequately
      studied. OBJECTIVE: To evaluate the incremental health care burden associated
      with dyspepsia among NVAF patients and its impact on warfarin treatment. METHODS:
      NVAF patients >= 18 years of age with continuous insurance coverage were
      identified (January 1, 2007, to December 31, 2009) from the MarketScan Commercial
      and Medicare Research databases. Patients with 1 inpatient or 2 outpatient
      dyspepsia diagnoses within 12 months following any NVAF diagnosis were grouped
      into the dyspeptic cohort, and patients without any dyspepsia diagnosis were
      grouped into the nondyspeptic cohort. Of the overall cohorts, patients were
      matched by key patient characteristics. Dyspepsia was further categorized as
      having a prior history of dyspepsia (chronic) or no dyspepsia (nonchronic) during
      the baseline period. Health care resource utilization, associated costs, and
      warfarin use were evaluated during a 12-month follow-up period. RESULTS: Of NVAF
      patients included in the study (N = 142,322), 10.4% were diagnosed with
      dyspepsia. After matching for key characteristics, NVAF patients with dyspepsia
      had significantly greater inpatient, outpatient, and prescription claims per
      patient year than those without dyspepsia (1.24 +/- 1.21 vs. 0.36 +/- 0.68, P <
      0.0001; 110.18 +/- 101.03 vs. 66.98 +/- 72.43, P < 0.0001; and 52.13 +/- 35.30
      vs. 44.29 +/- 32.41, P < 0.0001, respectively). This greater number of claims was
      reflected in higher annual inpatient, outpatient, and prescription payments
      ($23,610 +/- $54,748 vs. $5,509 +/- $19,142, P < 0.0001; $18,182 +/- $28,790 vs.
      $9,765 +/- $22,009, P < 0.0001; and $4,661 +/- $5,628 vs. $3,897 +/- $4,586, P <
      0.0001, respectively). NVAF patients with chronic dyspepsia were the least likely
      to take warfarin for stroke prevention. CONCLUSIONS: NVAF patients with dyspepsia
      experienced more all-cause hospitalizations and required more outpatient medical
      services, all associated with greater expenditures than NVAF patients without
      dyspepsia. Additionally, dyspepsia may be a barrier to warfarin use among NVAF
      patients.

PMID- 24684645
TI  - Budget impact analysis of antiepileptic drugs for Lennox-Gastaut syndrome.
AB  - BACKGROUND: In October 2011, clobazam was FDA-approved for adjunctive treatment
      of seizures associated with Lennox-Gastaut syndrome (LGS), a debilitating
      childhood epilepsy characterized by drop attacks, for patients 2 years and older.
      OBJECTIVE: To assess the budget impact of adding clobazam to an antiepileptic
      drug (AED) portfolio containing topiramate, lamotrigine, and rufinamide in a
      hypothetical, 100,000-member commercially insured health plan. METHODS: Patient
      characteristics and AED efficacy (decrease in drop-seizure frequency) were
      modeled with clinical data. Medical costs were derived from administrative claims
      data from a large U.S. managed health plan, with the assumption that 2.3% of drop
      seizures required medical care. Two-year budget impact was measured. Results were
      expressed as the overall difference in costs (medical and pharmacy) to a health
      plan and cost per member per month (PMPM) after addition of clobazam. Analyses of
      alternative scenarios were performed. RESULTS: With the assumption that 0.04% of
      the plan population had LGS, adding clobazam to the formulary resulted in cost
      savings of $98,059 in year 1 and $131,690 in year 2 (savings of $0.08 and $0.11
      PMPM, respectively). Analyses of alternative scenarios with lower seizure rates
      upon discontinuation or greater long-term efficacy for lamotrigine and topiramate
      did not substantially alter conclusions. The assumption that fewer drop seizures
      required medical care resulted in a savings of approximately $5,000 per year with
      clobazam, which suggested that medically attended drop seizures drive costs.
      CONCLUSIONS: Medically attended drop seizures are a major cost driver for LGS
      patients. Adding clobazam to a health plan formulary can have a positive overall
      budget impact through decreased medical costs associated with drop seizures.

PMID- 24684646
TI  - Expression of AID in malignant melanoma with BRAF(V600E) mutation.
AB  - BRAF-activating somatic mutations often exist in malignant melanoma. The
      underlying molecular mechanism of somatic BRAF mutation inductions remained to be
      clear. Activation-induced cytidine deaminase (AID), a member of a cytidine
      deaminase family, and APOBEC3B induce somatic mutations and recently have been
      indicated to be involved in the pathomechanism of several kinds of cancers. The
      aim of this study was to explore the expression level of AID and APOBEC3B in BRAF
      mutation- containing malignant melanoma. Immunohistochemical study demonstrated
      that 9 of 10 malignant melanomas with high AID expression had BRAF(V600E)
      mutation. Eight of them developed multiorgan metastases or multiple lymph node
      metastases afterwards. Although the size of the patient panel was small, the
      results indicate that there might be an association between AID expression and
      BRAF mutation in melanoma. 

PMID- 24684647
TI  - Erythema ab igne as an occupational skin disease (BK 5101).

PMID- 24684648
TI  - Risk assessment for carotid artery stenting.
AB  - Carotid artery stenting (CAS) is an effective and increasingly utilized therapy
      for carotid stenosis. Despite its safety, CAS does have procedural risks, which
      necessitates meticulous technique and careful patient selection for this
      procedure. A number of patient and anatomical characteristics have been shown to
      increase CAS risk, and recently, prediction models have been constructed to gauge
      individual patient risk objectively and comprehensively. This review discusses
      CAS risk assessment and offers a practical approach to the management of patients
      with carotid stenosis for which CAS is a viable treatment option. 

PMID- 24684649
TI  - Synthesis of enantiomerically enriched triarylmethanes by enantiospecific Suzuki
      Miyaura cross-coupling reactions.
AB  - The Suzuki-Miyaura cross-coupling of chiral, enantiomerically enriched dibenzylic
      boronic esters is described. The reaction proceeds with almost complete retention
      of stereochemistry, providing access to triarylmethanes, compounds that have high
      biological activity and are difficult to prepare in enantiomerically pure form
      using other methods. 

PMID- 24684650
TI  - Estimating how many undescribed species have gone extinct.
AB  - Because both descriptions of species and modern human-driven extinctions started
      around the same time (i.e., eighteenth century), a logical expectation is that a
      large proportion of species may have gone extinct without ever having been
      recorded. Despite this evident and widely recognized assumption, the loss of
      undescribed species has never been estimated. We quantified this loss for several
      taxonomic groups and regions for which undescribed species extinctions are likely
      to have occurred. Across a wide range of taxonomic groups, we applied known
      extinction rates computed from recorded species losses to assumed exponential
      decay in the proportion of species remaining undiscovered. Because all previous
      modeling attempts to project total species richness implicitly assumed that
      undescribed species extinctions could be neglected, we also evaluated the effect
      of neglecting them. Finally, because we assumed constant description and
      extinction probabilities, we applied our model to simulated data that did not
      conform to this assumption. Actual species losses were severely underestimated by
      considering only known species extinctions. According to our estimates, the
      proportion of undiscovered extinct species over all extinctions ranged from 0.15
      to 0.59, depending on the taxonomic group and the region considered. This means
      that recent extinctions may be up to twice as large as the number recorded. When
      species differed in their extinction or description probabilities, our model
      underestimated extinctions of undescribed species by up to 20%.

PMID- 24684652
TI  - The upregulation of immune checkpoint ligand PD-L1 in tumour microenvironment.

PMID- 24684654
TI  - Defects in chemically synthesized and thermally processed ZnO nanorods:
      implications for active layer properties in dye-sensitized solar cells.
AB  - We have carried out the effect of post annealing temperatures on the performance
      of solution-grown ZnO rods as photoanodes in dye-sensitized solar cells. Keeping
      our basic objective of exploring the effect of native defects on the performance
      of DSSC, we have synthesized ZnO rods having length in the range of 2-5 MUm by a
      modified sonication-induced precipitation technique. We performed extensive
      characterization on the samples annealed at various temperatures and confirmed
      that annealing at 300  degrees C results in ZnO rods with minimum native defects
      that have been identified as doubly ionized oxygen vacancies. The electron
      paramagnetic resonance measurements on the samples, on the other hand, confirmed
      the presence of shallow donors in the low temperature annealed samples. We also
      carried out electrochemical impedance measurements to understand the transport
      properties at different interfaces in the solar cell assembly. We could conclude
      that solution-processed ZnO rods annealed at 300  degrees C are better suited for
      fabricating DSSC with improved efficiency (1.57%), current density (5.11
      mA/cm(2)), and fill factor (45.29%). On the basis of our results, we were able to
      establish a close connection between the defects in the metal oxide electron
      transporting nano system and the DSSC performance. 

PMID- 24684655
TI  - Participation of functionally active plasma cells in acute rejection and response
      to therapy in renal allografts.
AB  - Acute rejection (AR) includes T-cell-mediated and antibody-mediated rejection.
      The inflammatory infiltrate comprised not only T cells but also varying amounts
      of B cells (CD20(+)) and plasma cells (CD138(+)). The latter are associated with
      poor clinical outcomes, but their functional status is not clear. The
      phosphorylation of the S6 ribosomal protein (p-S6RP) is present in cells that are
      metabolically active, thus identifying functionally active antibody-secreting
      plasma cells. This study was designed to evaluate the clinical significance of
      functionally active p-S6RP plasma cells in AR in renal allografts. Renal
      allografts with biopsy evidence of AR during 2006-2009 were included.
      Immunohistochemistry staining for CD20, CD138, and p-S6RP was performed on
      paraffin-embedded slides and scaled as 0-6. The response to antirejection
      treatment was assessed by the serum creatinine ratio (CrR) at rejection episode
      (time 0) and following treatment (4 and 12 weeks). Patients with lower scores (0
      2) were compared with a higher scored group (3-6). The T-test was conducted using
      statistical significance of p<0.05. A total of 28 patients (40.7 +/- 14.3 year;
      M:F=15:13) were diagnosed with acute T-cell-mediated rejection (I and II). The p
      S6RP staining in the high-score group had a significantly higher CrR (p<0.05)
      than the low-score group at the time of biopsy, 4 and 12 weeks following
      treatment. There was no significant difference in the CrR between groups for CD20
      or CD138 staining. Functional antibody-secreting p-S6RP plasma cells are actively
      participating in AR and associated with poor response to treatment in renal
      allografts.

PMID- 24684653
TI  - S-nitrosoglutathione reductase deficiency-induced S-nitrosylation results in
      neuromuscular dysfunction.
AB  - AIMS: Nitric oxide (NO) production is implicated in muscle contraction, growth
      and atrophy, and in the onset of neuropathy. However, many aspects of the
      mechanism of action of NO are not yet clarified, mainly regarding its role in
      muscle wasting. Notably, whether NO production-associated neuromuscular atrophy
      depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a
      matter of debate. Here, we aim at assessing this issue by characterizing the
      neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice
      that maintain the capability to produce NO, but are unable to reduce SNOs.
      RESULTS: We demonstrate that, without any sign of protein nitration, young GSNOR
      KO mice show neuromuscular atrophy due to loss of muscle mass, reduced fiber
      size, and neuropathic behavior. In particular, GSNOR-KO mice show a significant
      decrease in nerve axon number, with the myelin sheath appearing disorganized and
      reduced, leading to a dramatic development of a neuropathic phenotype.
      Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and
      myotubes, conditions that are reverted by N-acetylcysteine treatment.
      Nevertheless, although atrogene transcription is induced, and bulk autophagy
      activated, no removal of damaged mitochondria is observed. These events,
      alongside basal increase of apoptotic markers, contribute to persistence of a
      neuropathic and myopathic state. INNOVATION: Our study provides the first
      evidence that GSNOR deficiency, which affects exclusively SNOs reduction without
      altering nitrotyrosine levels, results in a clinically relevant neuromuscular
      phenotype. CONCLUSION: These findings provide novel insights into the involvement
      of GSNOR and S-nitrosylation in neuromuscular atrophy and neuropathic pain that
      are associated with pathological states; for example, diabetes and cancer.

PMID- 24684656
TI  - Linking admiration and adoration to self-expansion: different ways to enhance
      one's potential.
AB  - How is admiration different from adoration? We provided one answer to this
      question by examining the pathways through which admiration and adoration linked
      to self-expansion in a questionnaire and an experimental (autobiographical recall
      of emotion episodes) study. Both emotions were associated with increased
      potential efficacy to accomplish goals (i.e., self-expansion), but different
      action tendencies accounted for these links. While our emotion inductions did not
      successfully distinguish between admiration and adoration, we could statistically
      disentangle their effects through mediator models. In both studies, self-reported
      admiration linked to self-expansion through the tendency to emulate admired
      others. Adoration related to self-expansion through the tendency to affiliate
      with adored others. These findings were obtained after controlling for other
      emotions in response to the target person (awe, love, hope, benign envy) and
      mutuality of the relationship. Our findings also suggest that considering
      specific emotions (rather than undifferentiated positive affect) helps uncover
      different pathways to self-expansion. 

PMID- 24684657
TI  - Mechanism of macromolecular structure evolution in self-assembled lipid
      nanoparticles for siRNA delivery.
AB  - Lipid nanoparticles (LNPs) are a leading platform for therapeutic delivery of
      small interfering RNAs (siRNAs). Optimization of LNPs as therapeutic products is
      enabled by the development of structure-activity relationships (SAR) linking LNP
      physiochemical and macromolecular properties to bioperformance. Methods by which
      LNP properties can be rationally manipulated are thus critical enablers of this
      fundamental knowledge build. In this work, we present a mechanistic study of LNP
      self-assembly via a rapid antisolvent precipitation process and identify critical
      physiochemical and kinetic parameters governing the evolution of LNP three
      dimensional macromolecular structure as a biorelevant SAR feature. Using small
      angle X-ray scattering, LNPs are shown to undergo a temporal evolution in
      macromolecular structure during self-assembly, rearranging from initially
      disordered phases after precipitation into well-ordered structures following a
      necessary annealing stage of the assembly sequence. The ability of LNPs to
      undergo structural reorganization is shown to be effected by the chemical nature
      of the aqueous antisolvent used for precipitation. Antisolvents of varying
      buffering species differentially influence LNP macromolecular features, revealing
      a new participatory role of buffer ions in LNP self-assembly. Furthermore, the
      formation of macromolecular structure in LNPs is shown to improve the efficiency
      of siRNA encapsulation, thereby offering a simple, nonchemical route for
      preparation of high-payload LNPs that minimize the dose of lipid excipients. The
      developed LNP precipitation process and mechanistic understanding of self
      assembly are shown to be generalizable, enabling the production of LNPs with a
      tunable range of macromolecular features, as evidenced by the cubic, hexagonal,
      and oligo-lamellar phase LNPs exemplarily generated. 

PMID- 24684658
TI  - Resuscitation of neonates at 23 weeks' gestational age: a cost-effectiveness
      analysis.
AB  - OBJECTIVE: Resuscitation of infants at 23 weeks' gestation remains controversial;
      clinical practices vary. We sought to investigate the cost effectiveness of
      resuscitation of infants born 23 0/7-23 6/7 weeks' gestation. DESIGN: Decision
      analytic modeling comparing universal and selective resuscitation to non
      resuscitation for 5176 live births at 23 weeks in a theoretic U.S. cohort.
      Estimates of death (77%) and disability (64-86%) were taken from the literature.
      Maternal and combined maternal-neonatal utilities were applied to discounted life
      expectancy to generate QALYs. Incremental cost-effectiveness ratios were
      calculated, discounting costs and QALYs. Main outcomes included number of
      survivors, their outcome status and incremental cost-effectiveness ratios for the
      three strategies. A cost-effectiveness threshold of $100 000/QALY was utilized.
      RESULTS: Universal resuscitation would save 1059 infants: 138 severely disabled,
      413 moderately impaired and 508 without significant sequelae. Selective
      resuscitation would save 717 infants: 93 severely disabled, 279 moderately
      impaired and 343 without significant sequelae. For mothers, non-resuscitation is
      less expensive ($19.9 million) and more effective (127 844 mQALYs) than universal
      resuscitation ($1.2 billion; 126 574 mQALYs) or selective resuscitation ($845
      million; 125 966 mQALYs). For neonates, both universal and selective
      resuscitation were cost-effective, resulting in 22 256 and 15 134 nQALYS,
      respectively, versus 247 nQALYs for non-resuscitation. In sensitivity analyses,
      universal resuscitation was cost-effective from a maternal perspective only at
      utilities for neonatal death <0.42. When analyzed from a maternal-neonatal
      perspective, universal resuscitation was cost-effective when the probability of
      neonatal death was <0.95. CONCLUSIONS: Over wide ranges of probabilities for
      survival and disability, universal and selective resuscitation strategies were
      not cost-effective from a maternal perspective. Both strategies were cost
      effective from a maternal-neonatal perspective. This study offers a metric for
      counseling and decision-making for extreme prematurity. Our results could support
      a more permissive response to parental requests for aggressive intervention at 23
      weeks' gestation.

PMID- 24684659
TI  - The thematic structure of passenger comfort experience and its relationship to
      the context features in the aircraft cabin.
AB  - This paper describes passenger comfort as an experience generated by the cabin
      interior features. The findings of previous studies are affirmed regarding a set
      of 22 context features. Passengers experience a certain level of comfort when
      these features impact their body and elicit subjective perceptions. New findings
      characterise these perceptions in the form of eight themes and outline their
      particular eliciting features. Comfort is depicted as a complex construct derived
      by passengers' perceptions beyond the psychological (i.e. peace of mind) and
      physical (i.e. physical well-being) aspects, and includes perceptual (e.g.
      proxemics) and semantic (e.g. association) aspects. The seat was shown to have a
      focal role in eliciting seven of those themes and impacting comfort through its
      diverse characteristics. In a subsequent study, a group of aircraft cabin
      interior designers highlighted the possibility of employing the eight themes and
      their eliciting features as a framework for design and evaluation of new aircraft
      interiors. 

PMID- 24684660
TI  - Higher incidence of Epstein-Barr virus-induced lymphocyte transformation in
      multiple sclerosis.
AB  - OBJECTIVES: Epstein-Barr virus (EBV) infection is associated with multiple
      sclerosis (MS), and EBV may transform lymphoblastoid cell lines more frequently
      in MS patients than controls, but it is not clear whether this reflects a higher
      viral load or an enhanced ability to reactivate EBV. MATERIAL AND METHODS: MS
      patients and controls were examined for their B-cell subsets and during 16 weeks
      for spontaneous lymphocyte transforming events. RESULTS: MS patients had normal
      distribution of B-cell subsets, but a significantly higher incidence of B-cell
      transforming events, which occurred with kinetics similar to controls.
      CONCLUSIONS: The higher incidence suggests an increased frequency of latent EBV
      infected B cells in MS.

PMID- 24684661
TI  - Empathy development in adolescence predicts social competencies in adulthood.
AB  - This 23-year study explored the predictive associations between empathy
      development in adolescence and self-reported social competencies and outcomes in
      adulthood. Participants were 1,527 adults aged 35 years (48.3% female). The
      predictor variable (adolescent empathy) was measured yearly at the ages of 12 to
      16 years. The outcome variables (adult empathy, communication skills, social
      integration, relationship satisfaction, and conflicts in relationships) were
      measured at the age of 35 years. Five important results stand out. First,
      longitudinal measurement invariance was established for the measure of adolescent
      empathy. Second, empathy tended to increase during the adolescent years. Third,
      significant interindividual differences in level and change of adolescent empathy
      were found. Fourth, gender was related to level of adolescent empathy, favoring
      girls over boys. Fifth, not only level but also change in adolescent empathy
      predicted individual differences in social competencies in adulthood two decades
      later. These findings demonstrate that developmental processes that are relevant
      for adjustment reveal long-term social consequences beyond the adolescent years. 

PMID- 24684662
TI  - A randomized controlled trial of the effectiveness of a self-help psychoeducation
      programme on outcomes of outpatients with coronary heart disease: study protocol.
AB  - AIM: To develop and examine the effectiveness of a home-based self-help
      psychoeducation programme on health-related quality of life, stress level,
      anxiety and depression symptoms, self-efficacy, cardiac risk factors and health
      service use of outpatients with coronary heart disease. BACKGROUND: Hospital
      based cardiac rehabilitation programmes have been shown to improve, effectively,
      the quality of life of patients with coronary heart disease. However, a majority
      of these patients do not participate in these programmes, while those who do
      enrol in these programmes fail to complete the programmes. DESIGN: Randomized
      controlled trial with repeated measures. METHODS: This study was approved and
      received the grant in July 2013. A convenience sample of 128 coronary heart
      disease outpatients will be recruited from a tertiary hospital in Singapore.
      Participants are randomly assigned to the 4-week experimental group and will
      participate in the programme or the control group who will not participate in the
      programme. The outcome measures include the: 12-item Short Form Health Survey,
      Perceived Stress Scale, Hospital Anxiety and Depression Scale and General Self
      Efficacy Scale. Data will be collected at baseline, then 4 and 16 weeks from
      baseline. At the end, a process evaluation will be conducted to assess the
      acceptability, strengths and weaknesses of our programme based on the
      participants' perspectives. DISCUSSION: Our programme offers coronary heart
      disease patients an additional option to the existing cardiac rehabilitative
      services in Singapore hospitals. It aims to help them manage their disease
      effectively by reducing cardiac risk factors and improve their health-related
      quality of life and psychological well-being.

PMID- 24684663
TI  - Investigation of coarse-grained mappings via an iterative generalized Yvon-Born
      Green method.
AB  - Low resolution coarse-grained (CG) models enable highly efficient simulations of
      complex systems. The interactions in CG models are often iteratively refined over
      multiple simulations until they reproduce the one-dimensional (1-D) distribution
      functions, e.g., radial distribution functions (rdfs), of an all-atom (AA) model.
      In contrast, the multiscale coarse-graining (MS-CG) method employs a generalized
      Yvon-Born-Green (g-YBG) relation to determine CG potentials directly (i.e.,
      without iteration) from the correlations observed for the AA model. However, MS
      CG models do not necessarily reproduce the 1-D distribution functions of the AA
      model. Consequently, recent studies have incorporated the g-YBG equation into
      iterative methods for more accurately reproducing AA rdfs. In this work, we
      consider a theoretical framework for an iterative g-YBG method. We numerically
      demonstrate that the method robustly determines accurate models for both hexane
      and also a more complex molecule, 3-hexylthiophene. By examining the MS-CG and
      iterative g-YBG models for several distinct CG representations of both molecules,
      we investigate the approximations of the MS-CG method and their sensitivity to
      the CG mapping. More generally, we explicitly demonstrate that CG models often
      reproduce 1-D distribution functions of AA models at the expense of distorting
      the cross-correlations between the corresponding degrees of freedom. In
      particular, CG models that accurately reproduce intramolecular 1-D distribution
      functions may still provide a poor description of the molecular conformations
      sampled by the AA model. We demonstrate a simple and predictive analysis for
      determining CG mappings that promote an accurate description of these molecular
      conformations. 

PMID- 24684665
TI  - Rhodium-catalyzed direct C-H amidation of azobenzenes with sulfonyl azides: a
      synthetic route to sterically hindered ortho-substituted aromatic azo compounds.
AB  - A rhodium(III)-catalyzed direct ortho-amidation of azobenzenes with sulfonyl
      azides as the amino source is disclosed. This reaction exhibits a broad substrate
      scope, high functional group tolerance, and regioselectivity, providing a variety
      of sterically hindered ortho-substituted azobenzene derivatives in good to
      excellent yield. 

PMID- 24684664
TI  - Resistant starch film-coated microparticles for an oral colon-specific
      polypeptide delivery system and its release behaviors.
AB  - For the delivery of bioactive components to the colon, an oral colon-specific
      controlled release system coated with a resistant starch-based film through
      aqueous dispersion coating process was developed. Starch was modified by a high
      temperature-pressure reaction, enzymatic debranching, and retrogradation,
      resulting in a dramatic increase in the resistibility against enzymatic digestion
      (meaning the formation of resistant starch, specifically RS3). This increase
      could be associated with an increase in the relative crystallinity, a greater
      amount of starch molecular aggregation structure, and the formation of a compact
      mass fractal structure, resulting from the treatment. The microparticles coated
      with this RS3 film showed an excellent controlled release property. In
      streptozotocin (STZ)-induced type II diabetic rats, the RS3 film-coated insulin
      loaded microparticles exhibited the ability to steadily decrease the plasma
      glucose level initially and then maintain the plasma glucose level within the
      normal range for total 14-22 h with different insulin dosages after oral
      administration; no glycopenia or glycemic fluctuation was observed. Therefore,
      the potential of this new RS3 film-coated microparticle system has been
      demonstrated for the accurate delivery of bioactive polypeptides or protein to
      the colon. 

PMID- 24684666
TI  - A barley PHD finger transcription factor that confers male sterility by affecting
      tapetal development.
AB  - Controlling pollen development is of major commercial importance in generating
      hybrid crops and selective breeding, but characterized genes for male sterility
      in crops are rare, with no current examples in barley. However, translation of
      knowledge from model species is now providing opportunities to understand and
      manipulate such processes in economically important crops. We have used
      information from regulatory networks in Arabidopsis to identify and functionally
      characterize a barley PHD transcription factor MALE STERTILITY1 (MS1), which
      expresses in the anther tapetum and plays a critical role during pollen
      development. Comparative analysis of Arabidopsis, rice and Brachypodium genomes
      was used to identify conserved regions in MS1 for primer design to amplify the
      barley MS1 gene; RACE-PCR was subsequently used to generate the full-length
      sequence. This gene shows anther-specific tapetal expression, between late tetrad
      stage and early microspore release. HvMS1 silencing and overexpression in barley
      resulted in male sterility. Additionally, HvMS1 cDNA, controlled by the native
      Arabidopsis MS1 promoter, successfully complemented the homozygous ms1
      Arabidopsis mutant. These results confirm the conservation of MS1 function in
      higher plants and in particular in temperate cereals. This has provided the first
      example of a characterized male sterility gene in barley, which presents a
      valuable tool for the future control of male fertility in barley for hybrid
      development. 

PMID- 24684667
TI  - Potential of birds to serve as pathology-free models of type 2 diabetes, part 2:
      do high levels of carbonyl-scavenging amino acids (e.g., taurine) and low
      concentrations of methylglyoxal limit the production of advanced glycation end
      products?
AB  - In our previous publication, we reported on the advantages of using birds as a
      pathology-free model of type 2 diabetes mellitus (T2DM). Using this new
      perspective, we observed that birds are missing the RAGE gene, considered an
      important factor in the development of diabetic complications. In this article,
      we identify two additional Maillard reaction-related characteristics of birds
      that have the potential to account, in part, for avian ability to cope
      successfully with chronic hyperglycemia. First, compared to mammals, blood plasma
      of birds has significantly higher concentrations of taurine and other free amino
      acids that act as scavengers of reactive carbonyls. Second, there are also
      indications that avian blood plasma contains lower concentrations of
      methylglyoxal (MG) due, in part, to its decreased production by avian
      erythrocytes. Our deductions are based on relatively meager experimental data and
      are therefore speculative. One certain outcome of our study, however, is the idea
      that birds can be a useful model for the study of Maillard reactions and etiology
      of diabetic complications. We anticipate and hope that results of future studies
      will support the hypothesis identifying MG as a key intermediate in the etiology
      of diabetic complications. If this is indeed the case, then prevention and
      control of diabetic complications may become transformed into a more
      circumscribed, defined, and tractable problem whose goals will be to minimize the
      production of MG and to maximize its elimination by detoxification or scavenging.

PMID- 24684668
TI  - Social network ties beyond nonredundancy: an experimental investigation of the
      effect of knowledge content and tie strength on creativity.
AB  - Social network research emphasizes the access to nonredundant knowledge content
      that network ties provide. I suggest that some content is more beneficial than
      others and that tie strength may affect creativity for reasons other than the
      associated structure. That is, tie strength may affect how individuals process
      nonredundant knowledge. I investigate 2 types of knowledge content--information
      (i.e., facts or data) and frames (i.e., interpretations or impressions)--and
      explore whether tie strength influences their effect on creativity. Drawing on
      creativity theory, I employ an experimental design to provide greater theoretical
      clarity and to isolate causality. According to the results from 2 studies,
      distinct frames received from contacts facilitate creativity, but the effect of
      distinct information is more complex. When individuals receive distinct
      information from strong ties, it constrains creativity compared to distinct
      frames. Content from weak ties appears to facilitate creativity across all
      scenarios. The results of mediated moderation analysis indicate the effect of
      framing versus information for strong ties is driven by decision-making time, as
      an indicator of cognitive expansion.

PMID- 24684669
TI  - Lymph node metastasis after endoscopic submucosal dissection of a differentiated
      gastric cancer confined to the mucosa with an ulcer smaller than 30 mm.
AB  - In the expanded indications for endoscopic resection, Japanese guidelines for
      gastric cancer include differentiated cancers confined to the mucosa with an
      ulcer <30 mm. We describe a patient with lymph node metastasis after curative
      endoscopic submucosal dissection (ESD) for a tumor of this indication. The
      patient was a 70-year-old man with chronic hepatitis C. He underwent ESD for
      early gastric cancer in May 2010. Pathology revealed a moderately differentiated
      adenocarcinoma, 22 * 17 mm in size, that was confined to the mucosa with an
      ulcer. The horizontal and vertical margins were negative for the tumor. We
      diagnosed thiscase as curative resection of expanded indication and followed this
      patient with endoscopy, abdominal ultrasonography (AUS) or enhanced computed
      tomography (CT) approximately every 6 months. After 17 months, lymph node
      metastasis was detected with AUS and CT and diagnosed by endoscopic ultrasound
      guided fine-needle aspiration biopsy in August 2011. Distal gastrectomy with D2
      dissection was carried out in December 2011. Although it is low, the possibility
      of recurrence should be borne in mind after endoscopic treatment of early gastric
      cancer, despite its inclusion in the expanded indications for endoscopic
      resection. 

PMID- 24684671
TI  - Nickel-catalyzed reductive and borylative cleavage of aromatic carbon-nitrogen
      bonds in N-aryl amides and carbamates.
AB  - The nickel-catalyzed reaction of N-aryl amides with hydroborane or diboron
      reagents resulted in the formation of the corresponding reduction or borylation
      products, respectively. Mechanistic studies revealed that these reactions
      proceeded via the activation of the C(aryl)-N bonds of simple, electronically
      neutral substrates and did not require the presence of an ortho directing group. 

PMID- 24684670
TI  - The effect of tramadol and indomethacin coadministration on gastric barrier
      function in dogs.
AB  - BACKGROUND: Tramadol is a centrally acting analgesic that is often used in
      conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs). The effect of
      coadministration of tramadol and indomethacin on gastric barrier function in dogs
      is unknown. HYPOTHESIS/OBJECTIVES: That coadministration of a nonselective NSAID
      (indomethacin) and tramadol would decrease recovery of barrier function as
      compared with acid-injured, indomethacin-treated, and tramadol-treated mucosa.
      ANIMALS: Gastric mucosa of 10 humanely euthanized shelter dogs. METHODS: Ex vivo
      study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both.
      Gastric barrier function, prostanoid production, and cyclooxygenase expression
      were quantified. RESULTS: Indomethacin decreased recovery of transepithelial
      electrical resistance after injury, although neither tramadol nor the
      coadministration of the two had an additional effect. Indomethacin inhibited
      production of gastroprotective prostanoids prostaglandin E2 (acid-injured PGE2 :
      509.3 +/- 158.3 pg/mL, indomethacin + acid injury PGE2 : 182.9 +/- 93.8 pg/mL, P
      < .001) and thromboxane B2 (acid-injured TXB2 : 233.2 +/- 90.7 pg/mL,
      indomethacin + acid injury TXB2 : 37.9 +/- 16.8 pg/mL, P < .001), whereas
      tramadol had no significant effect (PGE2 P = .713, TXB2 P = .194). Neither drug
      had an effect on cyclooxygenase expression (COX-1 P = .743, COX-2 P = .705). Acid
      injury induced moderate to marked epithelial cell sloughing, which was unchanged
      by drug administration. CONCLUSIONS AND CLINICAL IMPORTANCE: There was no
      apparent interaction of tramadol and a nonselective cyclooxygenase in this ex
      vivo model. These results suggest that if there is an adverse interaction of the
      2 drugs in vivo, it is unlikely to be via prostanoid inhibition.

PMID- 24684672
TI  - Rheumatoid arthritis and the biological clock.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease of unknown cause and a chronic
      and progressive inflammatory disorder ensuing in genetically predisposed
      subjects, characterized by synovitis causing joint destruction, as well as
      inflammation in body organ systems, leading to anatomical alteration and
      functional disability. Immune competent cells, deregulated synoviocytes and
      cytokines play a key role in the pathophysiological mechanisms. The immune system
      function shows time-related variations related to the influence of the
      neuroendocrine system and driven by the circadian clock circuitry. Immune
      processes and symptom intensity in RA are characterized by oscillations during
      the day following a pattern of circadian rhythmicity. A cross-talk between
      inflammatory and circadian pathways is involved in RA pathogenesis and underlies
      the mutual actions of disruption of the circadian clock circuitry on immune
      system function as well as of inflammation on the function of the biological
      clock. Modulation of molecular processes and humoral factors mediating in RA the
      interplay between the biological clock and the immune response and underlying the
      rhythmic fluctuations of pathogenic processes and symptomatology could represent
      a promising therapeutic strategy in the future.

PMID- 24684673
TI  - Association between trauma patients' severity and critical care nursing workload
      in China.
AB  - The correlation between patients' severity and nursing workload for multiple
      trauma patients within the first 24 h of admission was explored in this study.
      Multiple trauma adult patients (n = 229) admitted in the emergency rescue room of
      a public hospital in China over a 1 year period were enrolled in this study. The
      worst values of the Acute Physiology and Chronic Health Evaluation-II scores and
      the Nursing Activity Score were collected during the first 24 h after admission.
      The predicted number of registered nurses was calculated for the corresponding
      severity groups. In the results, one-way ANOVA revealed that the Nursing Activity
      Score in the seven severity groups differed significantly. The total Acute
      Physiology and Chronic Health Evaluation-II score had a positive correlation with
      the Nursing Activity Score. The predicted number of registered nurses required
      was 0.6 for the low group, 0.7 for the moderate group, 1.0 for the severe group,
      and 1.1 for the extremely severe group. Patients' illness severity is an
      important indicator of nursing workload, especially in nurse staff allocation
      within the emergency department. 

PMID- 24684674
TI  - Interferon lambda-2 levels in sputum of patients with pulmonary Mycobacterium
      tuberculosis infection.
AB  - In humans, there are three members of type III interferon family, designated as
      IFN-lambda1 (IL-29), IFN-lambda2 (IL-28A) and IFN-lambda3 (IL-28B). Bacterial
      infections, including Mycobacterium tuberculosis infection, trigger the
      expression of interferon I and II genes, but little is known about their effect
      on IFN-lambda genes. It has been found that M. tuberculosis infection in A549
      lung epithelial cells stimulate upregulation of IFN-lambda2 genes in vitro. The
      aim of this study was to determine the IFN-lambda2 levels in sputum of patients
      with active pulmonary tuberculosis comparing with levels in healthy persons
      sputum and sputum of persons with latent tuberculosis. IFN-lambda2 level in the
      samples was quantified with sandwich enzyme-linked immunoassay kit for
      quantization of human IFN-lambda2 (IL-28A). The IFN-lambda2 level in sputum of
      patients with pulmonary tuberculosis was significantly higher comparing with IFN
      lambda2 levels in healthy group (P = 0.001) and latent tuberculosis group (P =
      0.005). Logistic regression analysis has shown that IFN-lambda2 level in sputum
      is related to culture result (OR = 4.14; 95% CI = 1.28-17.5; P = 0.019). There
      was the correlation between Bartlett score and IFN-lambda2 levels in group with
      pulmonary tuberculosis (r = 0.641; P < 0.01). In conclusion, we have found that
      the inflammatory cells in sputum can be source of IFN-lambda after receptor
      stimulation by M. tuberculosis components.

PMID- 24684675
TI  - Laparoscopic repair of incisional hernia in solid organ-transplanted patients:
      the method of choice?
AB  - Due to immunosuppressive (IS) therapy, incisional hernias are overrepresented in
      the organ-transplanted (Tx) population with larger defects, a high rate of
      recurrence, and a tendency toward more seromas and infectious problems. Thirty
      one Tx/IS patients with a control group of 70 non-IS patients with incisional
      hernia (6/7 recurrences) were included in a prospective interventional study.
      Both cohorts were treated with laparoscopic ventral hernia repair (LVHR). Follow
      up time and rate was 37 months and 95%. One hundred LVHR's were completed as
      there was one conversion in the Tx/IS group. No late infections or mesh removals
      occurred. Recurrence rates were 9.7% vs. 4.2% (P = 0.37) and the overall
      complication rates were 19% vs. 27% (P = 0.80). The Tx/IS group had a higher mesh
      protrusion rate (29% vs. 13%, P = 0.09), but also larger hernias. Polycystic
      kidney disease was overrepresented in the Tx cohort (44% of kidney-Tx).
      Incisional hernias in Tx/IS patients may be treated by LVHR with the same low
      complication rate and recurrence rate as non-IS patients. By LVHR, the highly
      problematic seroma/infection problems encountered in Tx/IS patients treated by
      conventional open technique seem almost eliminated. The minimally invasive
      procedure seems particularly rational in the Tx/Is population and should be the
      method of choice. (ClinicalTrials.gov number: NCT00455299, date: 5 May 2006).

PMID- 24684676
TI  - Role of CDH1 promoter methylation in colorectal carcinogenesis: a meta-analysis.
AB  - This meta-analysis was performed to evaluate the role of CDH1 promoter
      methylation in colorectal carcinogenesis. The PubMed, CISCOM, CINAHL, Web of
      Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched
      for relevant articles published before November 1st, 2013 without any language
      restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude
      odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Nine
      clinical cohort studies met all our inclusion criteria and were included in this
      meta-analysis. A total of 883 colorectal cancer (CRC) patients were assessed. Our
      meta-analysis results revealed that the frequencies of CDH1 promoter methylation
      in CRC tissues were higher than those in control tissues (OR=2.61, 95% CI=1.24
      5.50, p=0.012). A subgroup analysis by ethnicity showed that CDH1 promoter
      methylation was closely linked to the pathogenesis of CRC among Asians and
      Africans (Asians: OR=2.90, 95% CI=1.26-6.67, p=0.012; Africans: OR=3.81, 95%
      CI=1.56-9.34, p=0.003; respectively), but not among Caucasians (OR=1.68, 95%
      CI=0.24-11.72, p=0.598). A further subgroup analysis by type of control tissues
      suggested that CRC tissues also exhibited higher frequencies of CDH1 promoter
      methylation than those of normal and adjacent tissues (normal: OR=1.57, 95%
      CI=1.12-2.21, p=0.009; adjacent: OR=5.07, 95% CI=2.91-8.82, p<0.001;
      respectively). However, we found no evidence for any significant difference in
      the frequencies of CDH1 promoter methylation between CRC tissues and adenomas
      tissues (OR=1.18, 95% CI=0.74-1.90, p=0.485). Our findings provide empirical
      evidence that CDH1 promoter methylation may play an important role in colorectal
      carcinogenesis. Thus, CDH1 promoter methylation may be a useful biomarker for the
      early diagnosis of CRC. 

PMID- 24684677
TI  - Blue-green iridium(III) emitter and comprehensive photophysical elucidation of
      heteroleptic cyclometalated iridium(III) complexes.
AB  - Synthesis and photophysical properties of the highly emissive complex
      [Ir(Fppy)2(dmb)](+) are reported along with those of additional heteroleptic
      cyclometalated Ir(III) complexes, [Ir(ppy)2(NN)](PF6): FppyH = 2-(2,4
      difluorophenyl)pyridine; ppyH = 2-phenylpyridine; NN = 4,4'-dimethyl-2,2'
      bipyridine (dmb), 1,10-phenanthroline (phen), or 4,7-diphenyl-1,10-phenanthroline
      (Ph2phen). TD-DFT calculations and Franck-Condon emission spectral band shape
      analyses show that the broad and structureless emission from [Ir(Fppy)2(dmb)](+)
      in acetonitrile at 298 K mainly arises from a triplet metal-to-ligand charge
      transfer excited state, (3)MLCTIr(ppy)->NN. The emission maximum varies
      systematically with variations in electron-donating or -withdrawing substituents
      on both the NN and the Xppy ligands, and emission efficiencies are high, with an
      impressive phi ~ 1 for [Ir(Fppy)2(dmb)](+). At 77 K in
      propionitrile/butyronitrile (4/5, v/v), emission from [Ir(Fppy)2(dmb)](+) is
      narrow and highly structured consistent with a triplet ligand-centered transition
      ((3)LCNN) and an inversion in excited-state ordering between the (3)MLCTIr(ppy)
      >NN and (3)LCNN states. In a semirigid film of the
      poly(ethyleneglycol)dimethacrylate with nine ethylene glycol spacers, PEG-DMA550,
      emission from [Ir(Fppy)2(dmb)](+) is MLCT-based. The thermal sensitivity of the
      photophysical properties of this excited state points to a possible application
      as a temperature sensor in addition to its more known use in light-emitting
      devices. 

PMID- 24684678
TI  - Exfoliation of graphite into graphene in aqueous solutions of inorganic salts.
AB  - Mass production of high-quality graphene sheets is essential for their practical
      application in electronics, optoelectronics, composite materials, and energy
      storage devices. Here we report a prompt electrochemical exfoliation of graphene
      sheets into aqueous solutions of different inorganic salts ((NH4)2SO4, Na2SO4,
      K2SO4, etc.). Exfoliation in these electrolytes leads to graphene with a high
      yield (>85%, <=3 layers), large lateral size (up to 44 MUm), low oxidation degree
      (a C/O ratio of 17.2), and a remarkable hole mobility of 310 cm(2) V(-1) s(-1).
      Further, highly conductive graphene films (11 Omega sq(-1)) are readily
      fabricated on an A4-size paper by applying brush painting of a concentrated
      graphene ink (10 mg mL(-1), in N,N'-dimethylformamide). All-solid-state flexible
      supercapacitors manufactured on the basis of such graphene films deliver a high
      area capacitance of 11.3 mF cm(-2) and an excellent rate capability of 5000 mV s(
      1). The described electrochemical exfoliation shows great promise for the
      industrial-scale synthesis of high-quality graphene for numerous advanced
      applications. 

PMID- 24684679
TI  - The number of reduced alignments between two DNA sequences.
AB  - BACKGROUND: In this study we consider DNA sequences as mathematical strings.
      Total and reduced alignments between two DNA sequences have been considered in
      the literature to measure their similarity. Results for explicit representations
      of some alignments have been already obtained. RESULTS: We present exact,
      explicit and computable formulas for the number of different possible alignments
      between two DNA sequences and a new formula for a class of reduced alignments.
      CONCLUSIONS: A unified approach for a wide class of alignments between two DNA
      sequences has been provided. The formula is computable and, if complemented by
      software development, will provide a deeper insight into the theory of sequence
      alignment and give rise to new comparison methods. AMS SUBJECT CLASSIFICATION:
      Primary 92B05, 33C20, secondary 39A14, 65Q30.

PMID- 24684680
TI  - Foot deformation during walking: differences between static and dynamic 3D foot
      morphology in developing feet.
AB  - The complex functions of feet require a specific composition, which is
      progressively achieved by developmental processes. This development should take
      place without being affected by footwear. The aim of this study is to evaluate
      differences between static and dynamic foot morphology in developing feet. Feet
      of 2554 participants (6-16 years) were recorded using a new scanner system
      (DynaScan4D). Each foot was recorded in static half and full weight-bearing and
      during walking. Several foot measures corresponding to those used in last
      construction were calculated. The differences were identified by one-way ANOVA
      and paired Student's t-test. Static and dynamic values of each foot measure must
      be considered to improve the fit of footwear. In particular, footwear must
      account for the increase of forefoot width and the decrease of midfoot girth.
      Furthermore, the toe box should have a more rounded shape. The findings are
      important for the construction of footwear for developing feet. 

PMID- 24684681
TI  - Human umbilical cord blood-derived mesenchymal stromal cells display a novel
      interaction between P-selectin and galectin-1.
AB  - Human multipotent mesenchymal stromal/stem cells (MSCs) have been shown to exert
      immunomodulatory properties that have great potential in therapies for various
      inflammatory and autoimmune disorders. However, intravenous delivery of these
      cells is followed by massive cell entrapment in the lungs and insufficient homing
      to target tissues or organs. In targeting to tissues, MSCs and other therapeutic
      cells employ similar mechanisms as leucocytes, including a cascade of rolling and
      adhesion steps mediated by selectins, integrins and their ligands. However, the
      mechanisms of MSCs homing are not well understood. We discovered that P-selectin
      (CD62P) binds to umbilical cord blood (UCB)-derived MSCs independently of the
      previously known sialyl Lewis x (sLex)-containing ligands such as P-selectin
      glycoprotein ligand-1 (PSGL-1, CD162). By biochemical assays, we identified
      galectin-1 as a novel ligand for P-selectin. Galectin-1 has previously been shown
      to be a key mediator of the immunosuppressive effects of human MSCs. We conclude
      that this novel interaction is likely to play a major role in the
      immunomodulatory targeting of human UCB-derived MSCs. 

PMID- 24684683
TI  - Spontaneous neonatal thrombosis.

PMID- 24684684
TI  - Computational characterization of ketone-ketal transformations at the active site
      of matrix metalloproteinases.
AB  - We modeled the first steps of hydrolysis reactions of a natural oligopeptide
      substrate of matrix metalloproteinase MMP-2 as well as of a substrate analogue.
      In the latter, the scissile amide group is substituted by a ketomethylene group
      which can be transformed to the ketal group upon binding of this compound to the
      enzyme active site. According to our quantum mechanical-molecular mechanical
      (QM/MM) calculations, the reaction of the ketone-ketal transformation proceeds
      with a low energy barrier (3.4 kcal/mol) and a high equilibrium constant (10(4)).
      The reaction product with the ketal group formed directly at the active site of
      the enzyme works as an inhibitor that chelates the zinc ion. On the other hand,
      the oligopeptide mimetic retains molecular groups responsible for binding of this
      compound to the enzyme active site. This example illustrates a strategy to design
      MMP inhibitors in situ by using data on binding specificity of substrates to a
      particular type of MMP and details of the reaction mechanism. 

PMID- 24684682
TI  - ERK/MAPK regulates ERRgamma expression, transcriptional activity and receptor
      mediated tamoxifen resistance in ER+ breast cancer.
AB  - Selective estrogen receptor modulators such as tamoxifen (TAM) significantly
      improve breast cancer-specific survival for women with estrogen receptor-positive
      (ER+) disease. However, resistance to TAM remains a major clinical problem. The
      resistant phenotype is usually not driven by loss or mutation of the estrogen
      receptor; instead, changes in multiple proliferative and/or survival pathways
      over-ride the inhibitory effects of TAM. Estrogen-related receptor gamma
      (ERRgamma) is an orphan member of the nuclear receptor superfamily that promotes
      TAM resistance in ER+ breast cancer cells. This study sought to clarify the
      mechanism(s) by which this orphan nuclear receptor is regulated, and hence
      affects TAM resistance. mRNA and protein expression/phosphorylation were
      monitored by RT-PCR and western blotting, respectively. Site-directed mutagenesis
      was used to disrupt consensus extracellular signal-regulated kinase (ERK) target
      sites. Cell proliferation and cell-cycle progression were measured by flow
      cytometric methods. ERRgamma transcriptional activity was assessed by dual
      luciferase promoter-reporter assays. We show that ERRgamma protein levels are
      affected by the activation state of ERK/mitogen-activated protein kinase, and
      mutation of consensus ERK target sites impairs ERRgamma-driven transcriptional
      activity and TAM resistance. These findings shed new light on the functional
      significance of ERRgamma in ER+ breast cancer, and are the first to demonstrate a
      role for kinase regulation of this orphan nuclear receptor. 

PMID- 24684685
TI  - A robust, simple, high-throughput technique for time-resolved plant volatile
      analysis in field experiments.
AB  - Plant volatiles (PVs) mediate interactions between plants and arthropods,
      microbes and other plants, and are involved in responses to abiotic stress. PV
      emissions are therefore influenced by many environmental factors, including
      herbivore damage, microbial invasion, and cues from neighboring plants, and also
      light regime, temperature, humidity and nutrient availability. Thus, an
      understanding of the physiological and ecological functions of PVs must be based
      on measurements reflecting PV emissions under natural conditions. However, PVs
      are usually sampled in the artificial environments of laboratories or climate
      chambers. Sampling of PVs in natural environments is difficult, being limited by
      the need to transport, maintain and provide power to instruments, or use
      expensive sorbent devices in replicate. Ideally, PVs should be measured in
      natural settings with high replication, spatio-temporal resolution and
      sensitivity, and modest costs. Polydimethylsiloxane (PDMS), a sorbent commonly
      used for PV sampling, is available as silicone tubing for as little as 0.60 ? m(
      1) (versus 100-550 ? each for standard PDMS sorbent devices). Small pieces of
      silicone tubing (STs) of various lengths from millimeters to centimeters may be
      added to any experimental setting and used for headspace sampling, with little
      manipulation of the organism or headspace. STs have sufficiently fast absorption
      kinetics and large capacity to sample plant headspaces over a timescale of
      minutes to hours, and thus can produce biologically meaningful 'snapshots' of PV
      blends. When combined with thermal desorption coupled to GC-MS (a 40-year-old
      widely available technology), use of STs yields reproducible, sensitive, spatio
      temporally resolved quantitative data from headspace samples taken in natural
      environments. 

PMID- 24684686
TI  - Pro-tumorigenic effects of transforming growth factor beta 1 in canine
      osteosarcoma.
AB  - BACKGROUND: Transforming growth factor beta 1 (TGFbeta1) is a pleiotropic
      cytokine that contributes to reparative skeletal remodeling by inducing
      osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the
      largest bodily reservoir for latent TGFbeta1, and active osteoblasts express
      cognate receptors for TGFbeta1 (TGFbetaRI and TGFbetaRII). During malignant
      osteolysis, TGFbeta1 is liberated from eroded bone matrix and promotes local
      progression of osteotropic solid tumors by its mitogenic and prosurvival
      activities. HYPOTHESIS: Canine osteosarcoma (OS) cells will possess TGFbeta1
      signaling machinery. Blockade of TGFbeta1 signaling will attenuate pro
      tumorigenic activities in OS cells. Naturally occurring primary OS samples will
      express cognate TGFbeta1 receptors; and in dogs with OS, focal malignant
      osteolysis will contribute to circulating TGFbeta1 concentrations. ANIMALS:
      Thirty-three dogs with appendicular OS. METHODS: Expression of TGFbeta1 and its
      cognate receptors, as well as the biologic effects of TGFbeta1 blockade, was
      characterized in OS cells. Ten spontaneous OS samples were characterized for
      TGFbetaRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma
      TGFbeta1 concentrations were quantified and correlated with bone resorption.
      RESULTS: Canine OS cells secrete TGFbeta1, express cognate receptors, and
      TGFbeta1 signaling blockade decreases proliferation, migration, and vascular
      endothelial growth factor secretion. Naturally occurring OS samples abundantly
      and uniformly express TGFbetaRI/II, and in OS-bearing dogs, circulating TGFbeta1
      concentrations correlate with urine N-telopeptide excretion. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Canine OS cells possess TGFbeta1 signaling machinery,
      potentially allowing for the establishment of an autocrine and paracrine pro
      tumorigenic signaling loop. As such, TGFbeta1 inhibitors might impede localized
      OS progression in dogs.

PMID- 24684687
TI  - Topical nasal lysine aspirin in aspirin-sensitive and aspirin-tolerant chronic
      rhinosinusitis with nasal polyposis.
AB  - Chronic rhinosinusitis patients with nasal polyps can be aspirin sensitive or
      aspirin tolerant. The majority belong to the latter group. They tolerate intake
      of aspirin or other non-steroidal anti-inflammatory drugs, whereas aspirin
      sensitive patients have an adverse reaction (asthma, rhinitis and/or urticaria).
      Diagnosis of aspirin sensitivity is important for the patient, but is rarely
      undertaken in routine ENT or respiratory medicine practice. Treatment of nasal
      polyps is by a combination of medical therapy and surgery. Oral and topical
      steroids form the mainstay of medical therapy, which is aimed at reducing
      inflammation and symptom improvement. Surgery helps with polyps causing severe
      nasal obstruction. Despite these therapies, recurrences are common in aspirin
      sensitive patients. Any adjunctive therapy to prevent or prolong recurrence would
      be welcome. One such possibility is topical nasal lysine-aspirin. This is an area
      under current debate and this non-systematic review aims to provide evidence of
      its use, to date, in aspirin sensitive and aspirin tolerant nasal polyp patients.

PMID- 24684688
TI  - Neuroticism and attitudes toward action in 19 countries.
AB  - Although individuals scoring high on Neuroticism tend to avoid taking action when
      faced with challenges, Neuroticism is also characterized by impulsivity. To
      explore cognitive biases related to this costly behavior pattern, we tested
      whether individuals who rated themselves as higher in Neuroticism would evaluate
      the general concepts of action and inaction as, respectively, more negative and
      positive. We further investigated whether anxiety and depression would mediate
      and individualism-collectivism would moderate these relations in a large
      international sample. Participants (N = 3,827 college students; 69% female) from
      19 countries completed surveys measuring Neuroticism, attitudes toward action and
      inaction, depression, anxiety, and individualism-collectivism. Hierarchical
      linear models tested the above predictions. Neuroticism negatively correlated
      with attitudes toward action and positively correlated with attitudes toward
      inaction. Furthermore, anxiety was primarily responsible for emotionally unstable
      individuals' less positive attitudes toward action, and individuals who endorsed
      more collectivistic than individualistic beliefs showed a stronger negative
      association between Neuroticism and attitudes toward action. Researchers and
      practitioners interested in understanding and remediating the negative
      consequences of Neuroticism should pay greater attention to attitudes toward
      action and inaction, particularly focusing on their links with anxiety and
      individualism-collectivism.

PMID- 24684689
TI  - Comparative analysis of post-transplant lymphoproliferative disorder after kidney
      transplantation versus hematopoietic stem cell transplantation.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a major complication
      caused by immune-suppression after transplantation. Survival outcome is known to
      be poor and the characteristics are not fully understood because of its rare
      incidence. This single center retrospective study enrolled 41 adult PTLD patients
      after kidney-transplantation (KT, n = 28) and hematopoietic stem cell
      transplantation (HSCT, n = 13) from 1992 to 2012. We compared the characteristics
      and estimated the survival outcomes according to several factors [age-adjusted
      IPI (aaIPI), pathologic subtype, viral status, extranodal manifestation] and
      added some significant parameters to aaIPI scoring system. Post-HSCT-PTLD
      patients were younger and showed earlier onset, and viral status was more
      frequently identified. Ten-year OS of the entire group was 44% but the 10-year OS
      was not significantly different between post-KT-PTLD and post-HSCT-PTLD (39% vs.
      56%, P = 0.860). The time onset of PTLD and viral statuses were not meaningful,
      however, aaIPI, age > 50, extranodal manifestation and monomorphic subtype were
      predictive for OS. We used those factors for PTLD-specific scoring which showed
      intermediate-risk (HR = 7.1, P = 0.019) and high-risk (HR = 16.5, P = 0.001)
      presented worse OS compared to low-risk subgroup. Although the treatment
      strategies were heterogenous, this study showed comprehensive PTLD data between
      KT versus HSCT, and our PTLD-specific scoring might be validated by another
      larger studies.

PMID- 24684690
TI  - Single nucleotide polymorphisms in both endometriosis and ovarian cancer.

PMID- 24684691
TI  - In vitro and modelling approaches to risk assessment from the U.S. Environmental
      Protection Agency ToxCast programme.
AB  - A significant challenge in toxicology is the 'too many chemicals' problem. Human
      beings and environmental species are exposed to tens of thousands of chemicals,
      only a small percentage of which have been tested thoroughly using standard in
      vivo test methods. This study reviews several approaches that are being developed
      to deal with this problem by the U.S. Environmental Protection Agency, under the
      umbrella of the ToxCast programme (http://epa.gov/ncct/toxcast/). The overall
      approach is broken into seven tasks: (i) identifying biological pathways that,
      when perturbed, can lead to toxicity; (ii) developing high-throughput in vitro
      assays to test chemical perturbations of these pathways; (iii) identifying the
      universe of chemicals with likely human or ecological exposure; (iv) testing as
      many of these chemicals as possible in the relevant in vitro assays; (v)
      developing hazard models that take the results of these tests and identify
      chemicals as being potential toxicants; (vi) generating toxicokinetics data on
      these chemicals to predict the doses at which these hazard pathways would be
      activated; and (vii) developing exposure models to identify chemicals for which
      these hazardous dose levels could be achieved. This overall strategy is described
      and briefly illustrated with recent examples from the ToxCast programme. 

PMID- 24684692
TI  - The economic impact of multisystemic therapy through midlife: a cost-benefit
      analysis with serious juvenile offenders and their siblings.
AB  - OBJECTIVE: This study investigated the economic benefits of multisystemic therapy
      (MST) versus individual therapy (IT) using arrest data from 176 serious juvenile
      offenders and 129 of their closest-in-age siblings who participated, on average,
      25 years earlier in a randomized clinical trial (Borduin et al., 1995). METHOD:
      Two types of benefits of MST were evaluated: (a) The value to taxpayers was
      derived from measures of criminal justice system expenses (e.g., police and
      sheriffs' offices, court processing, community supervision), and (b) the value to
      crime victims was derived from measures of both tangible (e.g., property damage
      and loss, health care, lost productivity) and intangible (e.g., pain, suffering,
      reduced quality of life) losses. RESULTS: Reductions in criminality in the MST
      versus IT conditions were associated with lasting benefits to both taxpayers and
      crime victims, with cumulative benefits of MST estimated at $35,582 per juvenile
      offender and $7,798 per sibling. Overall, every dollar spent on MST recovered
      $5.04 in savings to taxpayers and crime victims in the 25 years following
      treatment. CONCLUSIONS: This study represents the most comprehensive cost-benefit
      analysis of an MST clinical trial to date and demonstrates that an evidence-based
      treatment such as MST can produce modest economic benefits well into adulthood.
      Implications of the authors' findings for policymakers and public service
      agencies are discussed.

PMID- 24684693
TI  - Comparison of endoscopic band ligation and endoclip closure of colonic
      perforation: technical feasibility and efficacy in an ex vivo pig model.
AB  - BACKGROUND AND AIM: Recent reports have indicated several instances of successful
      treatment of bowel perforation by using endoscopic band ligation (EBL) when
      treatment with endoclipping is unsuccessful, but this salvage method has not been
      investigated in any prospective model. Herein we aimed to compare the technical
      feasibility and efficacy of EBL and endoclip use in intraluminal closure of colon
      perforation, in an ex vivo model. METHODS: Standardized colonic perforations were
      created using fresh porcine colon and subsequently closed by full-thickness
      interrupted sutures, endoclip (QuickClip2(TM)), or EBL. Each closure site was
      tested with compressed air by using a digital pressure monitor for evaluating
      leak pressure. RESULTS: No significant differences were noted between the
      endoclip and EBL in leak pressures. Mean (+/- SD) pressures for air leakage from
      the perforations closed using the different devices were as follows: normal colon
      samples, 52.0 +/- 13.2 mmHg; perforations closed with hand-sewn sutures, 32.3 +/-
      8.3 mmHg; perforations closed with endoclipping, 53.5 +/- 22.7 mmHg; and
      perforations closed with EBL, 50.4 +/- 12.5 mmHg. Time taken for closure by EBL
      was significantly less than that for closure by endoclipping (3.2 +/- 1.7 min vs
      6.8 +/- 1.3 min, P < 0.01). Further, the number of devices used to achieve
      complete closure in the EBL group was lower than that with endoclipping (1.6 +/-
      0.5 vs 3.7 +/- 0.8, P < 0.01). CONCLUSION: Endoluminal closure of a 1.5-cm colon
      perforation with EBL decreased procedure time and was not inferior in leak
      pressure compared with endoclipping in this ex vivo porcine model.

PMID- 24684694
TI  - Religious affiliation and disparities in risk of non-communicable diseases and
      health behaviours: findings from the fourth Thai National Health Examination
      Survey.
AB  - This study aims to compare the health-related behaviours and risk of non
      communicable diseases (NCDs) between Muslims and non-Muslims in Thailand, a
      predominantly Buddhist country in which Muslims are the second largest religious
      group. Data from the fourth Thai National Health Examination Survey (NHES IV)
      conducted in 2009 were used to run multivariate survey logistic regression models
      with adjustment for age, gender and socio-economic status indicators. Data from
      20,450 respondents, of whom 807 (3.9%) were Muslims, were included in the study.
      Muslims were significantly more likely to have daily consumption of deep-fried
      food (adjusted odds ratio [OR]=1.35; 95% confidence interval [CI]=1.15-1.58) and
      packaged snacks (adjusted OR=1.55; 95% CI=1.30-1.86), and have inadequate control
      of hypercholesterolemia (adjusted OR=2.95; 95% CI=1.30-6.68). In conclusion, we
      found disparity in the majority of risk factors for NCDs between Muslim and non
      Muslim Thais.

PMID- 24684695
TI  - Prevalence of obstetric fistula: a population-based study in rural Pakistan.
AB  - OBJECTIVE: To estimate the prevalence of obstetric fistula, its duration and
      impact on women's daily life using robust data collection methods in a population
      based sample in rural Pakistan. DESIGN: A population-based, cross-sectional
      study. SETTING: A rural community in Sindh Province, Pakistan. POPULATION:
      Randomly selected women aged 15 years or older. METHODS: A multistage random
      sampling strategy was used to recruit the women. Lady Health Workers interviewed
      women in their own homes using a structured questionnaire to obtain symptom data.
      Women with symptoms of incontinence were then examined by female gynaecologists
      in their local health facilities to confirm obstetric fistula. MAIN OUTCOME
      MEASURE: Obstetric fistula confirmed by gynaecological examination. RESULTS:
      Among the 5064 women interviewed (96% response rate), 20 women with obstetric
      fistula were identified, showing a prevalence of 0.39% of all women (95%
      confidence interval [95% CI] 0.22-0.57%) and 0.45% of parous women (95% CI 0.25
      0.65%). Significantly more of the women with obstetric fistula compared with
      parous women without fistula were primiparae and aged <20 years. Of the women
      with obstetric fistula, 40% had had this for >5 years and 90% reported a major
      impact on their lives, yet only four had consulted a doctor, three of whom had
      failed repairs. CONCLUSIONS: The prevalence of obstetric fistula is high in rural
      Pakistan. Appropriate provision is needed for fistula repair to reduce the burden
      of the condition. Alongside this, the improvement of maternity care services is
      urgently needed to prevent its continued occurrence.

PMID- 24684696
TI  - Nurses' perception of senior managers at the front line: people working with
      clipboards.
AB  - AIM: To provide an original perspective on front-line nurses' perception of
      senior managers who are not nurses. BACKGROUND: A key element of new public
      management had been the drive for 'hands-on' professional management within the
      UK National Health Service, meaning the employment of mangers with managerial
      experience but little or no healthcare experience. DESIGN: An interpretive
      qualitative study, based on a single case study design with semi-structured
      interviews. METHODS: Semi-structured interviews were carried out with 31 front
      line Scottish National Health Service nurses exploring their perceptions of the
      role of managers between July-September 2010. RESULTS/FINDINGS: Nursing staff
      were often unsure of the responsibilities of managers and perceived that there
      were an unnecessarily high number of managers within the National Health Service.
      Nursing staff raised concerns over the non-clinical background of managers,
      including their ability to understand the pressures faced at the front line.
      CONCLUSIONS: The main reason for conflict between managers and nursing staff was
      their differing foci. Managers were seen to concentrate on decisions surrounding
      targets, audits and budgets with little consideration given to the impact of
      these decisions on patient care.

PMID- 24684697
TI  - Ni(I)/Ru(II) model for the Ni-L state of the [NiFe]hydrogenases: synthesis,
      spectroscopy, and reactivity.
AB  - This study describes the characterization of a mixed-valence Ru(II)/Ni(I)
      complex, a structural model for the Ni-L state of the [NiFe]hydrogenases. One
      electron oxidation of (cymene)Ru(MU-pdt)Ni(diphos) ([1](0), diphos = dppe,
      C2H4(PPh2)2; [2](0), diphos = dcpe, C2H4(P(C6H11)2)2] affords the mixed-valence
      cations [(cymene)Ru(pdt)Ni(diphos)](+) ([1](+) and [2](+)). Crystallographic and
      spectroscopic measurements indicate that these cations are described as
      Ru(II)/Ni(I). Although [1](0) and [1](+) are very similar structurally, the
      following changes are notable: the Ni-P distances elongate upon oxidation, and
      the Ru-Ni distance changes insignificantly. The molecular and electronic
      structures of the Ni center in [1](+) approaches that observed in the
      [NiFe]hydrogenases. Density functional theory calculations indicate that [1](0)
      is best described as Ru(II)/Ni(0), consistent with its oxidation to Ru(II)/Ni(I)
      in [1](+). The fast electron self-exchange rate of 10(7) M(-1) s(-1) between
      [1](0) and [1](+) suggests minor reorganization, more consistent with a
      Ni(0)/Ni(I) oxidation state change than a Ni(I)/Ni(II) couple. In solution,
      [1](+) slowly converts to [H1](+) and [1-H](+), with the latter being a complex
      of the thioaldehyde SCHCH2CH2S arising from C-H activation of the pdt backbone.
      Treatment of [1](+) with the H-atom abstracting reagent 2,2,6,6
      tetramethylpiperidine-1-oxy also gives [1-H](+). 

PMID- 24684699
TI  - Frequency of postural changes during sitting whilst using a desktop computer-
      exploring an analytical methodology.
AB  - BACKGROUND: Dynamic movement whilst sitting is advocated as a way to reduce
      musculoskeletal symptoms from seated activities. Conventionally, in ergonomics
      research, only a 'snapshot' of static sitting posture is captured, which does not
      provide information on the number or type of movements over a period of time. A
      novel approach to analyse the number of postural changes whist sitting was
      employed in order to describe the sitting behaviour of adolescents whilst
      undertaking computing activities. METHODS: A repeated-measures observational
      study was conducted. A total of 12 high school students were randomly selected
      from a conveniently selected school. Fifteen minutes of 3D posture measurements
      were recorded to determine the number of postural changes whilst using computers.
      RESULTS: Data of 11 students were able to be analysed. Large intra-subject
      variation of the median and IQR was observed, indicating frequent postural
      changes whilst sitting. CONCLUSION: Better understanding of usual dynamic
      postural movements whilst sitting will provide new insights into causes of
      musculoskeletal symptoms experienced by computer users.

PMID- 24684698
TI  - Molecular pedigree reconstruction and estimation of evolutionary parameters in a
      wild Atlantic salmon river system with incomplete sampling: a power analysis.
AB  - BACKGROUND: Pedigree reconstruction using genetic analysis provides a useful
      means to estimate fundamental population biology parameters relating to
      population demography, trait heritability and individual fitness when combined
      with other sources of data. However, there remain limitations to pedigree
      reconstruction in wild populations, particularly in systems where parent
      offspring relationships cannot be directly observed, there is incomplete sampling
      of individuals, or molecular parentage inference relies on low quality DNA from
      archived material. While much can still be inferred from incomplete or sparse
      pedigrees, it is crucial to evaluate the quality and power of available genetic
      information a priori to testing specific biological hypotheses. Here, we used
      microsatellite markers to reconstruct a multi-generation pedigree of wild
      Atlantic salmon (Salmo salar L.) using archived scale samples collected with a
      total trapping system within a river over a 10 year period. Using a simulation
      based approach, we determined the optimal microsatellite marker number for
      accurate parentage assignment, and evaluated the power of the resulting partial
      pedigree to investigate important evolutionary and quantitative genetic
      characteristics of salmon in the system. RESULTS: We show that at least 20
      microsatellites (ave. 12 alleles/locus) are required to maximise parentage
      assignment and to improve the power to estimate reproductive success and
      heritability in this study system. We also show that 1.5 fold differences can be
      detected between groups simulated to have differing reproductive success, and
      that it is possible to detect moderate heritability values for continuous traits
      (h2 ~ 0.40) with more than 80% power when using 28 moderately to highly
      polymorphic markers. CONCLUSION: The methodologies and work flow described
      provide a robust approach for evaluating archived samples for pedigree-based
      research, even where only a proportion of the total population is sampled. The
      results demonstrate the feasibility of pedigree-based studies to address
      challenging ecological and evolutionary questions in free-living populations,
      where genealogies can be traced only using molecular tools, and that significant
      increases in pedigree assignment power can be achieved by using higher numbers of
      markers.

PMID- 24684700
TI  - Suppressed expression of homotypic multinucleation, extracellular domains of
      CD172alpha (SIRP-alpha) and CD47 (IAP) receptors in TAMs upregulated by Hsp70
      peptide complex in Dalton's lymphoma.
AB  - CD172alpha and CD47 are members of glycoprotein expressed on macrophages and
      various immune cells, promote immune recognition and T cell stimulation that
      priming phagocytosis of pathogens and apoptotic bodies and malignant cell. Tumour
      releasing immunosuppressive factor promotes tumour growth and transforms the
      tumour resident M1 phenotype of macrophage to M2 phenotype (TAMs) that promotes
      tumour progression by downregulating the expression of different surface receptor
      including CD172alpha and CD47. Recent studies have reported that CD172alpha and
      CD47 are involved in the pathogenesis and promote malignancies such as lymphoma,
      leukaemia, melanoma, lung cancer and multiple myeloma, and their expression
      varies during infection and malignancies. Autologous Hsp70 is well recognized for
      its role in activating macrophages leading to enhance production of inflammatory
      cytokines. It has been observed that Hsp70 derived from normal tissues do not
      elicit tumour immunity, while Hsp70 preparation from tumour cell was able to
      elicit tumour immunity. However, the role of exogenous autologous hsp70 on the
      formation of giant cells is completely unknown. Therefore, in the present study,
      we sought to investigate the effect of Hsp70-peptide complex on the expression of
      CD172alpha and CD47 receptors in normal peritoneal macrophages (NMO) and TAMs.
      Finding shows that the expression of CD172alpha and CD47 enhances in TAMs and it
      reverts back the suppressed function of TAMs into M1 state of immunoregulatory
      phenotype that promotes tumour regression by enhanced multinucleation and
      phagocytosis of malignant cells and significantly enhances the homotypic fusion
      of macrophages and polykaryon formation in vitro by enhancing the expression of
      SIRPalpha and IAP. 

PMID- 24684701
TI  - Alcohol amination with ammonia catalyzed by an acridine-based ruthenium pincer
      complex: a mechanistic study.
AB  - The mechanistic course of the amination of alcohols with ammonia catalyzed by a
      structurally modified congener of Milstein's well-defined acridine-based PNP
      pincer Ru complex has been investigated both experimentally and by DFT
      calculations. Several key Ru intermediates have been isolated and characterized.
      The detailed analysis of a series of possible catalytic pathways (e.g., with and
      without metal-ligand cooperation, inner- and outer-sphere mechanisms) leads us to
      conclude that the most favorable pathway for this catalyst does not require metal
      ligand cooperation. 

PMID- 24684702
TI  - Early malaria resurgence in pre-elimination areas in Kokap Subdistrict, Kulon
      Progo, Indonesia.
AB  - BACKGROUND: Indonesia is among those countries committed to malaria eradication,
      with a continuously decreasing incidence of malaria. However, at district level
      the situation is different. This study presents a case of malaria resurgence
      Kokap Subdistrict of the Kulon Progo District in Yogyakarta Province, Java after
      five years of low endemicity. This study also aims to describe the community
      perceptions and health services delivery situation that contribute to this case.
      METHODS: All malaria cases (2007-2011) in Kulon Progo District were stratified to
      annual parasite incidence (API). Two-hundred and twenty-six cases during an
      outbreak (May 2011 to April 2012) were geocoded by household addresses using a
      geographic information system (GIS) technique and clusters were identified by
      SaTScan software analysis (Arc GIS 10.1). Purposive random sampling was conducted
      on respondents living inside the clusters to identify community perceptions and
      behaviour related to malaria. Interviews were conducted with malaria health
      officers to understand the challenges of malaria surveillance and control.
      RESULTS: After experiencing three consecutive years with API less than 1 per
      thousand, malaria in Kokap subdistrict increased almost ten times higher than API
      in the district level and five times higher than national API. Malaria cases were
      found in all five villages in 2012. One primary and two secondary malaria
      clusters in Hargotirto and Kalirejo villages were identified during the 2011-2012
      outbreak. Most of the respondents were positively aware with malaria signs and
      activities of health workers to prevent malaria, although some social economic
      activities could not be hindered. Return transmigrants or migrant workers
      entering to their villages, reduced numbers of village malaria workers and a
      surge in malaria cases in the neighbouring district contributed to the
      resurgence. CONCLUSION: Community perception, awareness and participation could
      constitute a solid foundation for malaria elimination in Kokap. However,
      decreasing number of village malaria workers and ineffective communication
      between primary health centres (PHCs) within boundary areas with similar malaria
      problems needs attention. Decentralization policy was allegedly the reason for
      the less integrated malaria control between districts, especially in the cross
      border areas. Malaria resurgence needs attention particularly when it occurs in
      an area that is entering the elimination phase.

PMID- 24684703
TI  - Influence of maternal body mass index on accuracy and reliability of external
      fetal monitoring techniques.
AB  - OBJECTIVE: To evaluate the performance of external electronic fetal heart rate
      and uterine contraction monitoring according to maternal body mass index. DESIGN:
      Secondary analysis of prospective equivalence study. SETTING: Three US urban
      teaching hospitals. SAMPLE: Seventy-four parturients with a normal term
      pregnancy. METHODS: The parent study assessed performance of two methods of
      external fetal heart rate monitoring (abdominal fetal electrocardiogram and
      Doppler ultrasound) and of uterine contraction monitoring (electrohystero-graphy
      and tocodynamometry) compared with internal monitoring with fetal scalp electrode
      and intrauterine pressure transducer. Reliability of external techniques was
      assessed by the success rate and positive percent agreement with internal
      methods. Bland-Altman analysis determined accuracy. We analyzed data from that
      study according to maternal body mass index. MAIN OUTCOME MEASURES: We assessed
      the relationship between body mass index and monitor performance with linear
      regression, using body mass index as the independent variable and measures of
      reliability and accuracy as dependent variables. RESULTS: There was no
      significant association between maternal body mass index and any measure of
      reliability or accuracy for abdominal fetal electrocardiogram. By contrast, the
      overall positive percent agreement for Doppler ultrasound declined (p = 0.042),
      and the root mean square error from the Bland-Altman analysis increased in the
      first stage (p = 0.029) with increasing body mass index. Uterine contraction
      recordings from electrohysterography and tocodynamometry showed no significant
      deterioration related to maternal body mass index. CONCLUSIONS: Accuracy and
      reliability of fetal heart rate monitoring using abdominal fetal
      electrocardiogram was unaffected by maternal obesity, whereas performance of
      ultrasound degraded directly with maternal size. Both electrohysterography and
      tocodynamometry were unperturbed by obesity.

PMID- 24684704
TI  - Apple MdABCF assists in the transportation of S-RNase into pollen tubes.
AB  - Self-incompatibility (SI) is a reproductive isolation mechanism in flowering
      plants. Plants in the Solanaceae, Rosaceae and Plantaginaceae belong to the
      gametophytic self-incompatibility type. S-RNase, which is encoded by a female
      specific gene located at the S locus, degrades RNA in the pollen tube and causes
      SI. Recent studies have provided evidence that S-RNase is transported non
      selectively into the pollen tube, but have not specified how this transportation
      is accomplished. We show here that the apple (Malus domestica) MdABCF protein,
      which belongs to group F of the ABC transporter family, assists in transportation
      of S-RNase into the pollen tube. MdABCF is located in the pollen tube membrane
      and interacts with S-RNase. S-RNase was unable to enter the pollen tube when
      MdABCF was silenced by antisense oligonucleotide transfection. Our results show
      that MdABCF assists in transportation of either self or non-self S-RNase into the
      pollen tube. Moreover, MdABCF coordinates with the cytoskeleton to transport S
      RNase. Blockage of S-RNase transport disrupts self-incompatibility in this
      system. 

PMID- 24684705
TI  - Early maternal age at first birth is associated with chronic diseases and poor
      physical performance in older age: cross-sectional analysis from the
      International Mobility in Aging Study.
AB  - BACKGROUND: Early maternal age at first birth and elevated parity may have long
      term consequences for the health of women as they age. Both are known risk
      factors for obstetrical complications with lifelong associated morbidities. They
      may also be related to diabetes and cardiovascular disease development. METHODS:
      We examine the relationship between early maternal age at first birth, defined as
      <=18 years of age, multiparity (>2 births), and poor physical performance (Short
      Physical Performance Battery<=8) in community samples of women between 65 and 74
      years of age from Canada, Albania, Colombia, and Brazil (N=1040). Data were
      collected in 2012 to provide a baseline assessment for a longitudinal cohort
      called the International Mobility in Aging Study. We used logistic regression and
      general linear models to analyse the data. RESULTS: Early maternal age at first
      birth is significantly associated with diabetes, chronic lung disease, high blood
      pressure, and poor physical performance in women at older ages. Parity was not
      independently associated with chronic conditions and physical performance in
      older age. After adjustment for study site, age, education, childhood economic
      adversity and lifetime births, women who gave birth at a young age had 1.75 (95%
      CI: 1.17-2.64) the odds of poor SPPB compared to women who gave birth>18 years of
      age. Adjustment for chronic diseases attenuated the association between early
      first birth and physical performance. Results were weaker in Colombia and Brazil,
      than Canada and Albania. CONCLUSIONS: This study provides evidence that
      adolescent childbirth may increase the risk of developing chronic diseases and
      physical limitations in older age. Results likely reflect both the biological and
      social consequences of early childbearing and if the observed relationship is
      causal, it reinforces the importance of providing contraception and sex education
      to young women, as the consequences of early pregnancy may be life-long.

PMID- 24684707
TI  - Three stages of lysozyme thermal stabilization by high and medium charge density
      anions.
AB  - Addition of high and medium charge density anions (phosphate, sulfate, and
      chloride) to lysozyme in pure water demonstrates three stages for stabilization
      of the protein structure. The first two stages have a minor impact on lysozyme
      stability and are probably associated with direct interaction of the ions with
      charged and partial charges on the protein's surface. There is a clear transition
      between the second and third stages; in the case of sodium chloride, disodium
      sulfate and disodium hydrogen phosphate this is at 550, 210, and 120 mM,
      respectively. Stabilization of lysozyme can be explained by the free energy
      required to hydrate the protein as it unfolds. At low ion concentrations, the
      protein's hydration layer is at equilibrium with the bulk water. After the
      transition, bulk water is depleted and the protein is competing for water with
      the ions. With competition for water between the protein and the ions at higher
      salt concentrations, the free energy required to hydrate the interior of the
      protein rises and it is this that stabilizes the protein structure. 

PMID- 24684706
TI  - Secondary antibody deficiency.
AB  - Secondary antibody deficiencies are defined by a quantitative or qualitative
      decrease in antibodies that occur most commonly as a consequence of renal or
      gastrointestinal immunoglobulin loss, hematological malignancies and
      corticosteroid, immunosuppressive or anticonvulsant medications. Patients with
      hematological malignancies or requiring immunosuppressive medications are known
      to be at increased risk of infection, but few studies directly address this
      relationship in the context of antibody deficiency. Immunoglobulin replacement
      therapy has been shown to be effective in reducing infections in primary and some
      secondary antibody deficiencies. The commonly encountered causes of secondary
      antibody deficiencies and their association with infection-related morbidity and
      mortality are discussed. Recommendations are made for screening and clinical
      management of those at risk.

PMID- 24684708
TI  - Strategic manipulation of an industrial biocatalyst--evolution of a cephalosporin
      C acylase.
AB  - Semi-synthetic cephalosporins are synthesized from the 7-amino cephalosporanic
      acid (7-ACA) nucleus produced from the antibiotic cephalosporin C (CephC). In
      recent years, a single-step enzymatic process in which CephC is directly
      converted into 7-ACA by a cephalosporin C acylase (CA) has attracted industrial
      interest because of the prospects of simplifying the process and reducing costs.
      CAs are members of the glutaryl acylase family that specifically use CephC as
      their substrate; however, known natural glutaryl acylases show very low activity
      on the antibiotic. We previously enhanced the catalytic efficiency on CephC of a
      glutaryl acylase from Pseudomonas N176 (named VAC) by a protein engineering
      approach, and solved the structures of the VAC, thus providing insight into the
      substrate binding and catalytic activity of CAs. However, the properties of such
      enzymes are not sufficient to encourage 7-ACA manufacturers to shift to single
      step enzymatic conversion of CephC. Here, we combine structural knowledge, semi
      rational design, computational approaches and evolution analysis to isolate VAC
      variants with altered substrate specificity (i.e. with a > 11,000-fold increase
      in specificity constant for CephC versus glutaryl-7-amino cephalosporanic acid,
      compared to wild-type) and with the highest kinetic efficiency so far obtained
      for a CA. Indeed, the H57betaS-H70betaS-L154betaY VAC variant shows the highest
      conversion of CephC into 7-ACA under conditions resembling those used at
      industrial level because of its high kinetic efficiency and the absence of
      substrate or product inhibition effects, and may be suitable for industrial
      application of the mono-step process for CephC conversion.

PMID- 24684709
TI  - At the centennial of Michaelis and Menten, competing Michaelis-Menten steps
      explain effect of GLP-1 on blood-brain transfer and metabolism of glucose.
AB  - Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic incretin hormone with
      both pancreatic and extrapancreatic effects. Studies of GLP-1 reveal significant
      effects in regions of brain tissue that regulate appetite and satiety. GLP-1
      mimetics are used for the treatment of type 2 diabetes mellitus. GLP-1 interacts
      with peripheral functions in which the autonomic nervous system plays an
      important role, and emerging pre-clinical findings indicate a potential
      neuroprotective role of the peptide, for example in models of stroke and in
      neurodegenerative disorders. A century ago, Leonor Michaelis and Maud Menten
      described the steady-state enzyme kinetics that still apply to the multiple
      receptors, transporters and enzymes that define the biochemical reactions of the
      brain, including the glucose-dependent impact of GLP-1 on blood-brain glucose
      transfer and metabolism. This MiniReview examines the potential of GLP-1 as a
      molecule of interest for the understanding of brain energy metabolism and with
      reference to the impact on brain metabolism related to appetite and satiety
      regulation, stroke and neurodegenerative disorders. These effects can be
      understood only by reference to the original formulation of the Michaelis-Menten
      equation as applied to a chain of kinetically controlled steps. Indeed, the
      effects of GLP-1 receptor activation on blood-brain glucose transfer and brain
      metabolism of glucose depend on the glucose concentration and relative affinities
      of the steps both in vitro and in vivo, as in the pancreas. 

PMID- 24684710
TI  - Outcomes of living donor liver transplantation for hepatitis C virus-positive
      recipients in Japan: results of a nationwide survey.
AB  - A nationwide survey of living donor liver transplantation (LDLT) for hepatitis C
      virus (HCV)-positive recipients was performed in Japan. A total of 514 recipients
      are reported and included in the study. The cumulative patient survival rate at 5
      and 10 years was 72% and 63%, respectively. Of the 514 recipients, 142 patients
      (28%) died until the end of the observation, among which the leading cause was
      recurrent hepatitis C (42 cases). According to Cox regression multivariate
      analysis, donor age (>40), non-right liver graft, acute rejection episode, and
      absence of a sustained virologic response were independent prognostic factors. Of
      the 514 recipients, 361 underwent antiviral treatment mainly with pegylated
      interferon and ribavirin (preemptive treatment in 150 patients and treatment for
      confirmed recurrent hepatitis in 211). The dose reduction rate and
      discontinuation rate were 40% and 42%, respectively, with a sustained virologic
      response rate of 43%. In conclusion, patient survival of HCV-positive recipients
      after LDLT was good, with a 10-year survival of 63%. Right liver graft might be
      preferable for HCV-positive recipients in an LDLT setting. 

PMID- 24684711
TI  - The impact of socio-economic status on net fertility during the historical
      fertility decline: a comparative analysis of Canada, Iceland, Sweden, Norway, and
      the USA.
AB  - We used micro-level data from the censuses of 1900 to investigate the impact of
      socio-economic status on net fertility during the fertility transition in five
      Northern American and European countries (Canada, Iceland, Norway, Sweden, and
      the USA). The study is therefore unlike most previous research on the historical
      fertility transition, which used aggregate data to examine economic correlates of
      demographic behaviour at regional or national levels. Our data included
      information on number of children by age, occupation of the mother and father,
      place of residence, and household context. The results show highly similar
      patterns across countries, with the elite and upper middle classes having
      considerably lower net fertility early in the transition. These patterns remain
      after controlling for a range of individual and community-level fertility
      determinants and geographical unobserved heterogeneity. 

PMID- 24684712
TI  - What is the role of bone biopsy in the management of adult dialysis patients?

PMID- 24684713
TI  - Recommendations for reporting the results of studies of instrument and scale
      development and testing.
AB  - Scales and instruments play an important role in health research and practice. It
      is important that studies that report on their psychometric properties do so in a
      way such that readers can understand what was done and what was found. This paper
      is a guide to writing articles about the development and assessment of these
      tools. It covers what should be in the abstract and how key words should be
      chosen. The article then discusses what should be in the main parts of the paper:
      the introduction, methods, results and discussion. In each of these parts, it
      suggests the statistical tests that should be used and how to report them. The
      emphasis throughout the paper is that reliability and validity are not fixed
      properties of a scale, but depend on an interaction among it, the population
      being evaluated and the circumstances under which the instrument is administered.

PMID- 24684714
TI  - Popularity among same-sex and cross-sex peers: a process-oriented examination of
      links to aggressive behaviors and depressive affect.
AB  - Popularity has been linked to heightened aggression and fewer depressive
      symptoms. The current study extends this literature by examining the unique
      contributions of same-sex and cross-sex popularity to children's development, as
      well as potential mediating processes. Third- and 4th-graders (212 boys, 250
      girls) provided data at 3 time points over 2 school years. Data included peer
      reported popularity, social exclusion, friendships, peer victimization, and
      aggression and self-reported social self-esteem and depressive affect. Same-sex
      and cross-sex popularity independently contributed to the prediction of
      aggression and depressive affect. Popularity was associated with heightened
      aggression through reduced social exclusion and was indirectly related to lower
      levels of depressive affect through increased friendships. For boys only, same
      sex popularity was further associated with dampened depressive affect through
      reduced social exclusion and peer victimization and increased social self-esteem.
      Findings are discussed in light of the potential tradeoffs associated with
      popularity in preadolescence.

PMID- 24684715
TI  - Neighborhood context and immigrant young children's development.
AB  - This study explored how neighborhood social processes and resources, relevant to
      immigrant families and immigrant neighborhoods, contribute to young children's
      behavioral functioning and achievement across diverse racial/ethnic groups. Data
      were drawn from the Project on Human Development in Chicago Neighborhoods, a
      neighborhood-based, longitudinal study with cohorts of children first seen at
      birth, 3 years, and 6 years of age and followed over 6 years (N = 3,209; 37%
      Mexican American, 33% Black, 15% White, 9% Puerto Rican, 4% other Latino, and 2%
      other races/ethnicities; 44% immigrant). Results of multilevel models suggest
      that the immigrant status of children's families was a more consistent moderator
      of associations between neighborhood processes and children's development than
      the immigrant concentration of their neighborhoods, but the nature of these
      associations depended on the outcome and racial/ethnic group considered.
      (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24684716
TI  - Friendship conflict and the development of generalized physical aggression in the
      early school years: a genetically informed study of potential moderators.
AB  - Several authors consider high and frequent conflicts between friends during
      childhood as a serious risk for subsequent conduct problems such as generalized
      physical aggression toward others (e.g., Kupersmidt, Burchinal, & Patterson,
      1995; Sebanc, 2003). Although it seems logical to assume that friendship conflict
      could have some negative consequences on children's behaviors, some scholars have
      suggested that a certain amount of conflict between friends may actually promote
      social adjustment (e.g., Laursen & Pursell, 2009). The aim of this study was to
      investigate the role of friendship conflict in regard to the development of
      generalized physical aggression toward others in the early school years (i.e.,
      from kindergarten to Grade 1), as well as the moderating role of relational
      (i.e., shared positive affect and dyadic conflict resolution skills) and personal
      (i.e., children's sex and genetic liability for aggression) characteristics in
      this context. The sample included 745 twins assessed through teacher, peer,
      child, and friend ratings in kindergarten and Grade 1. Friendship conflict in
      kindergarten was linearly related to an increase in boys' but not girls'
      generalized physical aggression. However, shared positive affect and conflict
      resolution skills mitigated the prospective associations between friendship
      conflict and generalized physical aggression. These results were independent of
      children's sex, genetic risk for physical aggression, and initial levels of
      generalized physical aggression in kindergarten. Fostering a positive
      relationship between friends at school entry may buffer against the risk
      associated with experiencing friendship conflict.

PMID- 24684717
TI  - The relationship between working memory for serial order and numerical
      development: a longitudinal study.
AB  - Despite numerous studies, the link between verbal working memory (WM) and
      calculation abilities remains poorly understood. The present longitudinal study
      focuses specifically on the role of serial order retention capacities, based on
      recent findings suggesting a link between ordinal processing in verbal WM and
      numerical processing tasks. Children were tested when they were in 3rd-year
      kindergarten (Time 1 [T1]), 1st grade (Time 2 [T2]), and 2nd grade of primary
      school (Time 3 [T3]), with WM tasks maximizing retention of serial order or item
      information, as well as with numerical judgment and calculation tasks. We
      observed that order WM measures at T1 provided a robust predictor of calculation
      abilities at T2 and T3. Numerical ordinal and magnitude judgment abilities were
      also associated with calculation abilities and this, independently of order WM
      abilities. This study highlights the important role of WM for order in early
      calculation acquisition, in addition to numerical ordinal and magnitude
      representations, and provides new perspectives for our understanding of the link
      between verbal WM and numerical abilities. (PsycINFO Database Record (c) 2014
      APA, all rights reserved). 

PMID- 24684718
TI  - Health-related quality of life after radical cystectomy and neobladder
      reconstruction in women: impact of voiding and continence status.
AB  - OBJECTIVES: To assess health-related quality of life, and the impact of night
      time incontinence and chronic urinary retention on health-related quality of life
      in women with bladder cancer after radical cystectomy and orthotopic neobladder.
      METHODS: The study included 74 women who underwent radical cystectomy and
      orthotopic neobladder, and completed 1 year of follow up. Health-related quality
      of life was evaluated using the questionnaires of the European Organization for
      Research and Treatment of Cancer-Quality of Life Questionnaire and the Functional
      Assessment of Cancer Therapy bladder cancer-specific form. Health-related quality
      of life was compared with an age-matched control group. The impact of night-time
      incontinence and chronic urinary retention on health-related quality of life was
      assessed. RESULTS: The study group included 18 completely continent patients with
      spontaneous voiding, 29 with night-time incontinence and 27 with chronic urinary
      retention. The study group was statistically significantly lower in all domains
      of health-related quality of life than the control group. In all domains of the
      European Organization for Research and Treatment of Cancer-Quality of Life
      Questionnaire and Functional Assessment of Cancer Therapy bladder cancer-specific
      form, completely continent women were comparable with those with chronic urinary
      retention. Women with night-time incontinence had a significantly worse health
      related quality of life than completely continent women, shown by the mean global
      health score (P = 0.038), social functioning score (P = 0.012), pain European
      Organization for Research and Treatment of Cancer-Quality of Life Questionnaire
      score (P = 0.04), and functional well-being Functional Assessment of Cancer
      Therapy bladder cancer-specific form (P = 0.049) score. CONCLUSIONS: After
      radical cystectomy and orthotopic neobladder in women, health-related quality of
      life is lower than that of the normal population. Night-time incontinence has a
      negative impact on social life and most domains of health-related quality of
      life. Thus, night-time incontinence has a higher social impact than chronic
      urinary retention.

PMID- 24684719
TI  - Maternal blood pressure and heart rate response to pelvic floor muscle training
      during pregnancy.
AB  - OBJECTIVES: To assess whether maternal blood pressure (BP) and heart rate (HR)
      change significantly in response to pelvic floor muscle training during
      pregnancy. DESIGN: Longitudinal exploratory study with repeated measurements.
      SAMPLE: Twenty-seven nulliparous healthy women of mean age 23.3 years (range 18
      36) and mean body mass index 23.4 (range 23.1-29.5). METHODS: Individual
      supervised pelvic floor muscle training from gestational week 20 till 36 with
      assessment of BP and HR at gestational weeks 20, 24, 28, 32 and 36. MAIN OUTCOME
      MEASURES: Systolic and diastolic BP was measured before and after each training
      session and HR was monitored during each session. RESULTS: Pelvic floor muscle
      training did not change BP. 77% (n = 21) of participants exceeded 70% of
      estimated maximum HR during at least one session. The time for exceeding 70% of
      estimated maximum HR was between 2.2 and 3.2 % of the total exercise session.
      Increases in BP and HR from gestational weeks 20 till 36 were within normal
      limits for pregnant women. CONCLUSIONS: Pelvic floor muscle training in
      nulliparous sedentary pregnant women does not increase BP. It significantly
      increases HR during the exercise sessions, but only for a limited period of time
      and with no negative long-term effect on BP or HR.

PMID- 24684720
TI  - A portable system with sample rate of 250 Hz for characterization of knee and hip
      angles in the sagittal plane during gait.
AB  - BACKGROUND: Gait analysis and research have been developed to obtain
      characteristics of movement patterns of people while walking. However,
      traditional measuring systems present different drawbacks that reduce their use
      and application. Among those drawbacks one can find: high price, low sampling
      frequency and limiting number of steps to be analyzed. Traditional measuring gait
      systems carry out their measurement at frequencies oscillating between 60 to 100
      Hz. It can be argued about the need of higher sampling rates for gait
      measurements. However small displacements of the knee or hip for example, cannot
      be seen with low frequencies required a more detailed sampling and higher
      frequency sampling. Bearing this in mind, in this paper is presented a 250 Hz
      system based on accelerometers for gait measurement, and the particularities of
      knee and hip angles during gait are highlighted. METHODS: The system was designed
      with a PCI data acquisition card instrumented with an FPGA to achieve a rate
      sample of 250 Hz. The accelerometers were placed in thighs and legs to calculate
      the joint angles of hip and knee in the sagittal plane. The angles were estimated
      using the acceleration polygon method without integrating the acceleration and
      without filters. RESULTS: The gait of thirty healthy people of Mexican phenotype
      was analyzed over a flat floor free of obstacles. The results showed the gait
      phases and particularities associated with the walking style and people's
      laterality; the movement patterns were similar in the thirty persons. Based on
      the results, the particularities as the maximum amplitude in the angles and the
      shape in the movement patterns were related to the anthropometry and people
      phenotype. CONCLUSIONS: The sampling frequency was essential to record 340
      samples in single gait cycle and so registering the gait cycle with its
      particularities. In this work were recorded an average of 8 to 10 gait cycles,
      and the results showed variation regarding works carried out in biomechanics
      laboratories; this variation was related to the method and reference frame used
      to obtain the joint angles and the accuracy of measurement system.

PMID- 24684721
TI  - Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and
      primary human microglia.
AB  - BACKGROUND: The pathological hallmark of multiple sclerosis (MS) is myelin
      phagocytosis. It remains unclear why microglia and macrophages demyelinate axons
      in MS, but previously found or yet-unknown changes in the myelin of MS patients
      could contribute to this process. We therefore studied whether myelin from normal
      appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than
      myelin from control donors. METHODS: Myelin was isolated from 11 MS and 12
      control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to
      quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages
      and by primary human microglia was quantified with flow cytometry. Whereas myelin
      uptake by THP-1 macrophages reached a plateau after approximately 24 hours,
      uptake by primary human microglia showed an almost linear increase over a 72-hour
      period. Data were statistically analyzed with the Mann-Whitney U test. RESULTS:
      MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6
      hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P
      = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P
      = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106
      for total myelin uptake). This enhanced uptake was not due to differences in the
      oxidation status of the myelin. Interestingly, myelin phagocytosis correlated
      negatively with the age of myelin donors, whereas the age of microglia donors
      showed a positive trend with myelin phagocytosis. CONCLUSIONS: Myelin isolated
      from normal-appearing white matter of MS donors was phagocytosed more efficiently
      than was myelin isolated from control brain donors by both THP-1 macrophages and
      primary human microglia. These data indicate that changes in MS myelin might
      precede phagocyte activation and subsequent demyelination in MS. Identifying
      these myelin changes responsible for enhancing phagocytic ability could be an
      interesting therapeutic target to prevent or inhibit formation or expansion of MS
      lesions. Moreover, during aging, microglia enhance their phagocytic capacity for
      myelin phagocytosis, but myelin reduces its susceptibility for uptake.

PMID- 24684722
TI  - Characterization of the pigmented shell-forming proteome of the common grove
      snail Cepaea nemoralis.
AB  - BACKGROUND: With a diversity of pigmented shell morphotypes governed by Mendelian
      patterns of inheritance, the common grove snail, Cepaea nemoralis, has served as
      a model for evolutionary biologists and population geneticists for decades.
      Surprisingly, the molecular mechanisms by which C. nemoralis generates this
      pigmented shelled diversity, and the degree of evolutionary conservation present
      between molluscan shell-forming proteomes, remain unknown. RESULTS: Here, using
      next generation sequencing and high throughput proteomics, we identify and
      characterize the major proteinaceous components of the C. nemoralis shell, the
      first shell-proteome for a pulmonate mollusc. The recent availability of several
      marine molluscan shell-proteomes, and the dataset we report here, allow us to
      identify 59 evolutionarily conserved and novel shell-forming proteins. While the
      C. nemoralis dataset is dominated by proteins that share little to no similarity
      with proteins in public databases, almost half of it shares similarity with
      proteins present in other molluscan shells. In addition, we could not find any
      indication that a protein (or class of proteins) is directly associated with
      shell pigmentation in C. nemoralis. This is in contrast to the only other
      partially characterized molluscan-shell pigmentation mechanism employed by the
      tropical abalone Haliotis asinina. CONCLUSIONS: The unique pulmonate shell
      forming proteome that we report here reveals an abundance of both mollusc
      specific and pulmonate-specific proteins, suggesting that novel coding sequences,
      and/or the extensive divergence of these sequences from ancestral sequences,
      supported the innovation of new shell types within the Conchifera. In addition,
      we report here the first evidence that molluscs use independently evolved
      mechanisms to pigment their shells. This proteome provides a solid foundation
      from which further studies aimed at the functional characterization of these
      shell-forming proteins can be conducted.

PMID- 24684723
TI  - Monitoring of Hypocalcaemia & Hyperglycemia predictive consequences of
      Thyroidectomy.
AB  - BACKGROUND: Hyperglycemia and hypocalcaemia have separately been attributed to
      adverse outcomes in critically ill patients. The study was aim determine whether
      hyperglycemia and hypocalcaemia together post-operative effect of thyroidectomy
      and evaluate the gender & age impact on the extend of clinical condition.
      METHODS: All the patients underwent thyroidectomy in the duration of 1st Jan 2012
      till 30th June, 2013 in HPP and HUSM Kelantan, Malaysia. Serum evaluation has
      been made on 4 consecutive reading with duration of 6 hours. The predictive trend
      has been established to identify the hypokalemic and hyperglycemic condition.
      Ethical approvals & Patients' consent forms have been made prior to conduct this
      study. RESULTS: The incidence of hyperglycemia [>= 150 mg/dl(8.3 mmol/L)] and
      hypocalcaemia (serum calcium < 8.5 mg/dl (2.2 mmol/L)] were 39.4% and 43.9%
      respectively. Hyperglycemia and hypocalcaemia associated with age and length of
      stay, significant association has been found among pre-operative diagnosis as
      well. The interaction of hyperglycemia and hypocalcaemia did not separate effects
      on mortality. CONCLUSION: As demonstrated, the prevalence of hyperglycemia and
      hypocalcaemia in post-thyroidectomy patients is considerable high. Also, the
      linear association pattern has been shown. However, considering the disease
      severity, the association of hyperglycemia and hypocalcaemia with surgical ward
      indicators of morbidity could not be verified.

PMID- 24684725
TI  - Antibiotic use and resistance.

PMID- 24684726
TI  - Transcriptomic and lipidomic profiles of glycerolipids during Arabidopsis flower
      development.
AB  - Flower glycerolipids are the yet-to-be discovered frontier of the lipidome.
      Although ample evidence suggests important roles for glycerolipids in flower
      development, stage-specific lipid profiling in tiny Arabidopsis flowers is
      challenging. Here, we utilized a transgenic system to synchronize flower
      development in Arabidopsis. The transgenic plant PAP1::AP1-GR ap1-1 cal-5 showed
      synchronized flower development upon dexamethasone treatment, which enabled
      massive harvesting of floral samples of homogenous developmental stages for
      glycerolipid profiling. Glycerolipid profiling revealed a decrease in
      concentrations of phospholipids involved in signaling during the early
      development stages, such as phosphatidic acid and phosphatidylinositol, and a
      marked increase in concentrations of nonphosphorous galactolipids during the late
      stage. Moreover, in the midstage, phosphatidylinositol 4,5-bisphosphate
      concentration was increased transiently, which suggests the stimulation of the
      phosphoinositide metabolism. Accompanying transcriptomic profiling of relevant
      glycerolipid metabolic genes revealed simultaneous induction of multiple
      phosphoinositide biosynthetic genes associated with the increased
      phosphatidylinositol 4,5-bisphosphate concentration, with a high degree of
      differential expression patterns for genes encoding other glycerolipid-metabolic
      genes. The phosphatidic acid phosphatase mutant pah1 pah2 showed flower
      developmental defect, suggesting a role for phosphatidic acid in flower
      development. Our concurrent profiling of glycerolipids and relevant metabolic
      gene expression revealed distinct metabolic pathways stimulated at different
      stages of flower development in Arabidopsis. 

PMID- 24684724
TI  - CD44 standard and CD44v10 isoform expression on leukemia cells distinctly
      influences niche embedding of hematopoietic stem cells.
AB  - BACKGROUND: A blockade of CD44 is considered a therapeutic option for the
      elimination of leukemia initiating cells. However, anti-panCD44 can interfere
      with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)
      specific antibody can inhibit leukemia growth without attacking hematopoiesis. As
      a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). METHODS: The
      therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after
      intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated
      the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on
      hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a
      focus on adhesion, migration, cell cycle progression and apoptosis resistance.
      RESULTS: Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti
      panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher
      efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger
      antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis.
      Instead, EL4 compete with HSC niche embedding. This has consequences on
      quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44,
      too, more efficiently affected embedding of HSC than of EL4 in the bone marrow
      stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did
      not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the
      HSC--bone marrow stroma crosstalk. CONCLUSION: The therapeutic effect of anti
      panCD44 and anti-CD44v10 is based on stimulation of antibody-dependent cellular
      cytotoxicity. The superiority of anti-CD44v10 is partly due to blocking CD44v10
      stimulated osteopontin expression that could drive HSC out of the niche. However,
      the main reason for the superiority of anti-CD44v10 relies on neither EL4-v10 nor
      anti-CD44v10 severely interfering with HSC--stroma cell interactions that, on the
      other hand, are affected by EL4 and anti-panCD44. Anti-panCD44 disturbing HSC
      embedding in the osteogenic niche weakens its therapeutic effect towards EL4.
      Thus, as far as leukemic cells express CD44v isoforms, the therapeutic use of
      anti-panCD44 should be avoided in favor of CD44v-specific antibodies.

PMID- 24684727
TI  - Vacuum-assisted closure (VAC)-Instill((r)) with continuous irrigation for the
      treatment of Mycoplasma hominis mediastinitis.
AB  - A 56-year-old patient who underwent ascending aorta replacement postoperatively
      developed mediastinitis with atypical Mycoplasma hominis. We present the first
      successful treatment of M. hominis mediastinitis after cardiac surgery with
      vacuum-assisted closure (VAC)-Instill((r)) therapy combined with dilute
      antiseptic irrigation for bacterial eradication. 

PMID- 24684728
TI  - Factors associated with recent HIV testing among younger gay and bisexual men in
      New Zealand, 2006-2011.
AB  - BACKGROUND: Understanding HIV testing behaviour is vital to developing evidence
      based policy and programming that supports optimal HIV care, support, and
      prevention. This has not been investigated among younger gay, bisexual, and other
      men who have sex with men (YMSM, aged 16-29) in New Zealand. METHODS: National
      HIV sociobehavioural surveillance data from 2006, 2008, and 2011 was pooled to
      determine the prevalence of recent HIV testing (in the last 12 months) among
      YMSM. Factors associated with recent testing were determined using manual
      backward stepwise multivariate logistic regression. RESULTS: Of 3,352 eligible
      YMSM, 1,338 (39.9%) reported a recent HIV test. In the final adjusted model, the
      odds of having a recent HIV test were higher for YMSM who were older, spent more
      time with other gay men, reported multiple sex partners, had a regular partner
      for 6-12 months, reported high condom use with casual partners, and disagreed
      that HIV is a less serious threat nowadays and that an HIV-positive man would
      disclose before sex. The odds of having a recent HIV test were lower for YMSM who
      were bisexual, recruited online, reported Pacific Islander or Asian ethnicities,
      reported no regular partner or one for >3 years, were insertive-only during anal
      intercourse with a regular partner, and who had less HIV-related knowledge.
      CONCLUSION: A priority for HIV management should be connecting YMSM at risk of
      infection, but unlikely to test with appropriate testing services. New
      generations of YMSM require targeted, culturally relevant health promotion that
      provides accurate understandings about HIV transmission and prevention.

PMID- 24684729
TI  - Glucose-6-phosphate dehydrogenase deficiency: an unusual cause of acute jaundice
      after paracetamol overdose.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest human enzyme
      defect causing haemolytic anaemia after exposure to specific triggers.
      Paracetamol-induced haemolysis in G6PD deficiency is a rare complication and
      mostly reported in children. We report the first case (to the best of our
      knowledge) of acute jaundice without overt clinical features of a haemolytic
      crisis, in an otherwise healthy adult female following paracetamol overdose, due
      to previously undiagnosed G6PD deficiency. It is important that clinicians
      consider this condition when a patient presents following a paracetamol overdose
      with significant and disproportionate jaundice, without transaminitis or
      coagulopathy. 

PMID- 24684731
TI  - Sensitive colorimetric visualization of perfluorinated compounds using
      poly(ethylene glycol) and perfluorinated thiols modified gold nanoparticles.
AB  - In this work, we have developed a novel sensing strategy employing mixed
      poly(ethylene glycol)-terminated (PEG-thiols) and perfluoroalkyl-terminated (F
      thiols) alkanethiols modified gold nanoparticles (Au@PEG-F NPs) as a probe to
      detect perfluorinated compounds (PFCs) from water samples. PEG-thiols with high
      density and long carbon chains make the Au NPs probe well-dispersed in solution
      and stable even in high concentration of salt solution; F-thiols provide specific
      fluorous-fluorous interactions to PFCs, which results in adsorption of PFCs on
      Au@PEG-F NPs. The adsorbed PFCs cause the aggregation of Au@PEG-F NPs probes and
      thus induce the insolubility of probes and precipitation directly from reaction
      solution due to the superhydrophobicity of perfluorocarbon monolayers, leading to
      color and absorbance response of the assay to PFCs. The preparation of the Au@PEG
      F NPs probe is very simple, and the colorimetric assay based on this mechanism
      for the detection of PFCs is selective and convenient. Combined with UV-vis
      spectrophotometry, the assay demonstrates good sensitivities to PFCs with wide
      linear range. In the designed concentration range, the response of the
      colorimetric assay to long-chain PFCs (perfluoroalkyl chain >=7) is discerned
      even as the concentration of these PFCs is as low as 10 MUg L(-1). This low-cost
      and sensitive assay shows great potential to measure total PFCs in water samples.
      To the best of our knowledge, this is the first application of the specific
      fluorous-fluorous interactions and Au NPs based probes for colorimetric
      recognition for PFCs. 

PMID- 24684730
TI  - Comparative analysis of single and combined APP/APLP knockouts reveals reduced
      spine density in APP-KO mice that is prevented by APPsalpha expression.
AB  - Synaptic dysfunction and synapse loss are key features of Alzheimer's
      pathogenesis. Previously, we showed an essential function of APP and APLP2 for
      synaptic plasticity, learning and memory. Here, we used organotypic hippocampal
      cultures to investigate the specific role(s) of APP family members and their
      fragments for dendritic complexity and spine formation of principal neurons
      within the hippocampus. Whereas CA1 neurons from APLP1-KO or APLP2-KO mice showed
      normal neuronal morphology and spine density, APP-KO mice revealed a highly
      reduced dendritic complexity in mid-apical dendrites. Despite unaltered
      morphology of APLP2-KO neurons, combined APP/APLP2-DKO mutants showed an
      additional branching defect in proximal apical dendrites, indicating redundancy
      and a combined function of APP and APLP2 for dendritic architecture. Remarkably,
      APP-KO neurons showed a pronounced decrease in spine density and reductions in
      the number of mushroom spines. No further decrease in spine density, however, was
      detectable in APP/APLP2-DKO mice. Mechanistically, using APPsalpha-KI mice
      lacking transmembrane APP and expressing solely the secreted APPsalpha fragment
      we demonstrate that APPsalpha expression alone is sufficient to prevent the
      defects in spine density observed in APP-KO mice. Collectively, these studies
      reveal a combined role of APP and APLP2 for dendritic architecture and a unique
      function of secreted APPs for spine density. 

PMID- 24684732
TI  - Beyond the scope of free-Wilson analysis. 2: Can distance encoded R-group
      fingerprints provide interpretable nonlinear models?
AB  - In a recent study, we presented a novel quantitative-structure-activity
      relationship (QSAR) approach, combining R-group signatures and nonlinear support
      vector-machines (SVM), to build interpretable local models for congeneric
      compound sets. Here, we outline further refinements in the fingerprint scheme for
      the purpose of analyzing and visualizing structure-activity relationships (SAR).
      The concept of distance encoded R-group signature descriptors is introduced, and
      we explore the influence of different signature encoding schemes on both
      interpretability and predictive power of the SVM models using ten public data
      sets. The R-group and atomic gradients provide a way to interpret SVM models and
      enable detailed analysis of structure-activity relationships within substituent
      groups. We discuss applications of the method and show how it can be used to
      analyze nonadditive SAR and provide intuitive and powerful SAR visualizations. 

PMID- 24684733
TI  - Progression of breast cancer cells was enhanced by endocrine-disrupting
      chemicals, triclosan and octylphenol, via an estrogen receptor-dependent
      signaling pathway in cellular and mouse xenograft models.
AB  - In the present study, we determined whether two endocrine-disrupting chemicals
      (EDCs), triclosan (TCS) and octylphenol (OP), are able to alter the expression of
      two cell cycle regulators, cyclin D1 and p21, in both in vitro and mouse breast
      cancer models. In addition, we determined whether the stimulatory effects of OP
      or TCS on breast cancer progression may be associated with an estrogen receptor
      (ER)-mediated signaling pathway. Altered expressions of cyclin D1 and p21 were
      observed in MCF-7 human breast cancer cells treated with TCS and OP, which is
      linked to the G1/S transition of cell cycle, leading to cell proliferation. In a
      xenograft mouse model, breast tumor masses were established following exposure to
      TCS and OP for 8 weeks. In these animals, the tumor cells with BrdU-positive
      nuclei were increased by treatment with 17beta-estradiol (E2), OP, and TCS
      compared to that of a control (corn oil), suggesting that TCS and OP increase DNA
      synthesis during the S phase in tumor cells. Increased level of cyclin D1 protein
      by TCS and OP was also observed in vivo, implying that the effects of these EDCs
      possessing estrogenic activity alter the expression of genes related to cancer
      progression. It was of interest that the effects of TCS and OP were reversed by
      ICI 182,780, an ER antagonist, indicating that EDC-induced activities are
      mediated by an ER-dependent signaling pathway. Taken together, these results
      suggest that TCS and OP may promote breast cancer progression, via an ER-mediated
      signaling cascade. 

PMID- 24684734
TI  - Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised
      control trial: CLONEMESI.
AB  - OBJECTIVE: To study the efficacy of transdermal clonidine in the treatment of
      severe refractory hyperemesis gravidarum (HG), the most severe illness of
      pregnancy. DESIGN: The study had a randomised, double -blind, placebo-controlled,
      cross-over design (RCT). SETTING: Single tertiary referral hospital after
      admission of patients. SAMPLE: Twelve women of gestational age 6-12 weeks and a
      major grade of HG clinical severity who were unresponsive to standard antiemetic
      treatment. METHODS: The patients were randomly treated with and without the
      active drug (5 mg patch) for two consecutive periods of 5 days. The patients were
      allocated to a random list to receive first placebo and then active drug or the
      other way round. Other antiemetic drugs were administered on a scheduled or as
      needed basis. All patients received intravenous hydration and thiamine
      supplementation. MAIN OUTCOME MEASURES: Pregnancy Unique Quantification of Emesis
      (PUQE) and visual analog scale (VAS) clinical scores, positive morning urine
      ketonuria, number of doses of standard antiemetic drugs required, and number of
      days off intravenous therapy were compared in the two periods. RESULTS:
      Transdermal clonidine led to a significantly greater improvement compared with
      placebo of the primary (PUQE score P = 0.026 CI 0.43-3.24; VAS score P = 0.010 CI
      2.17-12.83) and secondary outcome measures. A reduction of blood pressure was
      reported for systolic 6 mmHg P = 0.01 and diastolic 3 mmHg P = 0.055.
      CONCLUSIONS: This preliminary RCT demonstrates the efficacy of transdermal
      clonidine in the treatment of severe HG, leading to a significant reduction of
      symptoms and reducing the need for other supportive measures and medications.

PMID- 24684735
TI  - Downregulation of DAB2IP results in cell proliferation and invasion and
      contributes to unfavorable outcomes in bladder cancer.
AB  - The DOC-2/DAB2 interactive protein (DAB2IP) is a member of the Ras GTPase
      activating protein family. It has been shown to be often downregulated and a poor
      prognostic factor in several human malignancies. In this study, we analyzed the
      clinicopathological features and outcomes of DAB2IP expression in 135 patients
      with urothelial carcinoma of the bladder (UCB) treated by radical cystectomy plus
      bilateral lymph node dissection, and evaluated the effect of DAB2IP knockdown in
      vitro using the MTT method, colony formation assay, cell cycle assay, and cell
      migration and invasive assay. We found low expression of DAB2IP was significantly
      associated with high pathological stage (P = 0.002), high pathological grade (P =
      0.02), tumor size more than 3 cm (P = 0.04), and presence of histological
      variants (P = 0.01). DAB2IP was an independent prognostic factor of disease
      recurrence (hazard ratio, 2.67; P = 0.034) and cancer-specific survival (hazard
      ratio, 2.79; P = 0.038). Knockdown of DAB2IP could promote cell proliferation,
      migration, and invasion. Downregulation of DAB2IP could activate the ERK and Akt
      pathways and was correlated with the expression of epithelial-mesenchymal
      transition markers, such as E-cadherin and vimentin. In conclusion,
      downregulation of DAB2IP is associated with features of biologically aggressive
      UCB and results in cell proliferation, migration, and invasion of bladder cancer.
      DAB2IP may serve as a promising biomarker in patients with UCB treated by radical
      cystectomy and bilateral lymph node dissection.

PMID- 24684737
TI  - Treatment adherence: a hurdle for real-life effectiveness in psoriasis?

PMID- 24684736
TI  - A cross-sectional study of well water arsenic and child IQ in Maine
      schoolchildren.
AB  - BACKGROUND: In recent studies in Bangladesh and elsewhere, exposure to arsenic
      (As) via drinking water is negatively associated with performance-related aspects
      of child intelligence (e.g., Perceptual Reasoning, Working Memory) after
      adjustment for social factors. Because findings are not easily generalizable to
      the US, we examine this relation in a US population. METHODS: In 272 children in
      grades 3-5 from three Maine school districts, we examine associations between
      drinking water As (WAs) and intelligence (WISC-IV). RESULTS: On average, children
      had resided in their current home for 7.3 years (approximately 75% of their
      lives). In unadjusted analyses, household well WAs is associated with decreased
      scores on most WISC-IV Indices. With adjustment for maternal IQ and education,
      HOME environment, school district and number of siblings, WAs remains
      significantly negatively associated with Full Scale IQ and Perceptual Reasoning,
      Working Memory and Verbal Comprehension scores. Compared to those with WAs < 5
      MUg/L, exposure to WAs >= 5 MUg/L was associated with reductions of approximately
      5-6 points in both Full Scale IQ (p < 0.01) and most Index scores (Perceptual
      Reasoning, Working Memory, Verbal Comprehension, all p's < 0.05). Both maternal
      IQ and education were associated with lower levels of WAs, possibly reflecting
      behaviors (e.g., water filters, residential choice) limiting exposure. Both WAs
      and maternal measures were associated with school district. CONCLUSIONS: The
      magnitude of the association between WAs and child IQ raises the possibility that
      levels of WAs >= 5 MUg/L, levels that are not uncommon in the United States, pose
      a threat to child development.

PMID- 24684738
TI  - Non-adherence and measures to improve adherence in the topical treatment of
      psoriasis.
AB  - Psoriasis is a chronic, recurrent immune-mediated skin disease with a 2-3%
      prevalence in the Western population, which severely affects patients' quality of
      life and poses a considerable socioeconomic challenge. The majority of
      individuals have psoriasis in limited areas and topical products are the mainstay
      of therapy according to existing guidelines. It is known that medication
      adherence rates are lower for topical treatment than for systemic treatment. Poor
      medication adherence is a major multidimensional problem for patients with
      chronic disorders as it is associated with unfavourable treatment outcomes,
      increased risk for development of concomitant diseases and inefficient use of
      health resources. Despite four decades of adherence research and the large number
      of studies that have identified the importance of medication non-adherence, there
      are relatively few studies reporting and designing effective strategies to
      improve adherence. The aim of this article was to report and describe non
      adherence in the topical treatment of psoriasis, the factors that might
      contribute to this phenomenon, and which interventions have so far been developed
      for the management of chronic conditions. This article proposes that given that
      the barriers to medication adherence are complex and varied, solutions to improve
      adherence and thus clinical outcomes must be multifaceted and must also provide
      the possibility to be tailored according to each patient's individual needs. Such
      an individualized and comprehensive adherence-enhancing intervention would
      probably enable the successful long-term management of this disabling chronic
      condition. 

PMID- 24684739
TI  - Pooled safety analysis of calcipotriol plus betamethasone dipropionate gel for
      the treatment of psoriasis on the body and scalp.
AB  - The fixed combination calcipotriol plus betamethasone dipropionate gel is a first
      line treatment for psoriasis vulgaris. The objective was to perform a large-scale
      assessment of tolerability of fixed combination gel (Cal/BD). Analysis was
      performed on pooled 8-week safety data from nine clinical trials evaluating once
      daily Cal/BD treatment of scalp (n = 6) and body (n = 3) psoriasis.
      Pharmacovigilance data were also assessed. Patients were treated with Cal/BD [n =
      1953 (scalp), n = 824 (body)], betamethasone dipropionate gel (BD; n = 1214, n =
      562), calcipotriol gel (Cal; n = 979, n = 175), gel vehicle (VEH; n = 173, n =
      226), calcipotriol scalp solution [n = 104 (scalp only)] and tacalcitol ointment
      [TAC; n = 184 (body only)]. Most adverse events (AEs) were mild-moderate
      severity. The proportion of scalp psoriasis patients with >=1 AE was lowest with
      Cal/BD (35% versus 38-57%). A similar proportion was found with Cal/BD for body
      psoriasis (32%), however, lower proportions were reported with BD (24%) and Cal
      (29%). The most common AEs with Cal/BD included nasopharyngitis, pruritus and
      upper respiratory tract infection (2-5% of patients). Overall, only 5% of
      patients treated with Cal/BD reported >=1 lesional/perilesional AEs: the lowest
      incidence versus scalp comparators (6-19%) and second lowest to BD (3%) for body
      psoriasis. Similarly, Cal/BD treatment resulted in the lowest incidence of >=1
      adverse drug reactions (ADRs) in scalp psoriasis patients (8% versus 9-27%) and
      second lowest to BD (6% versus 4%) for body psoriasis. Overall, incidence of
      serious AEs (SAEs) was low (0-1%). Data received postmarketing through
      spontaneous reporting revealed that SAEs reported more than once with Cal/BD
      treatment were psoriasis (n = 5); and alopecia, erythrodermic psoriasis,
      pruritus, skin atrophy and urticaria (n = 2 each). In this large subset of
      patients treated with Cal/BD, incidence of AEs and ADRs is consistently low. This
      analysis provides further evidence of the good tolerability of the fixed
      combination gel as treatment for psoriasis vulgaris. 

PMID- 24684740
TI  - Expert recommendations: the use of the fixed combination calcipotriol and
      betamethasone dipropionate gel for the topical treatment of psoriasis.
AB  - Treatment non-adherence is a general challenge and a complex problem. It is a key
      factor that impacts the 'real-life' effectiveness of topical treatments for
      chronic disorders, such as psoriasis. Here, we provide our expert opinion on the
      real-life effectiveness of topical psoriasis treatment, using the fixed
      combination gel (Daivobet((r)) gel; calcipotriol plus betamethasone dipropionate)
      as a case study. The fixed combination gel is a first-line topical treatment for
      mild-to-moderate psoriasis, developed to be the gold-standard therapy for
      psoriasis patients. This fixed combination gel is an effective and well-tolerated
      topical psoriasis treatment that the majority of our patients prefer to the
      ointment formulation. We assessed our real-life experience and considered any
      gaps between daily practice and clinical trials data. We recommend a multifaceted
      approach to improve real-life effectiveness and bridge the gap between
      investigational trials and treatment reality and propose the following
      recommendations: (1) educate primary healthcare providers on how to effectively
      manage topical psoriasis treatment and the patients who use the treatment; (2)
      educate the patient on why treatment needs to be maintained, even when symptoms
      improve; and (3) provide a supportive environment that will not allow the patient
      to feel abandoned. A patient-centric approach may improve adherence, which will
      lead to patients receiving more effective treatment for psoriasis. 

PMID- 24684741
TI  - Conversion to mammalian target of rapamycin inhibitors increases risk of de novo
      donor-specific antibodies.
AB  - In kidney transplantation, conversion to mammalian target of rapamycin (mTOR)
      inhibitors may avoid calcineurin inhibitor (CNI) nephrotoxicity, but its impact
      on post-transplant allo-immunization remains largely unexplored. This
      retrospective cohort study analyzed the emergence of donor-specific antibodies
      (DSA) in kidney transplant recipients relative to their immunosuppressive
      therapy. Among 270 recipients without pretransplant immunization who were
      screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after
      CNI withdrawal. DSA emergence was increased in patients who were converted to
      mTOR inhibitors (HR 2.4; 95% CI 1.06-5.41, P = 0.036). DSA were mainly directed
      against donor HLA-DQB1 antigens. The presence of one or two DQ mismatches was a
      major risk factor for DQ DSA (HR 5.32; 95% CI 1.58-17.89 and HR 10.43; 95% CI
      2.29-47.56, respectively; P < 0.01). Rejection episodes were more likely in
      patients converted to mTOR inhibitors, but this difference did not reach
      significance (16% vs. 7.9%, P = 0.185). Concerning graft function, no significant
      change was observed one year after conversion (P = 0.31). In conclusion,
      conversion to mTOR inhibitors may increase the risk of developing class II DSA,
      especially in the presence of DQ mismatches: this strategy may favor chronic
      antibody-mediated rejection and thus reduce graft survival. 

PMID- 24684743
TI  - Reconstruction after skin cancer excision through a dermal induction template:
      our experience.
AB  - Dermal substitutes offer alternative approaches for wounds of all thicknesses
      where sufficient donation sites are not available for self-grafts. Several dermal
      substitutes are described in literature. This study included 20 patients treated
      with a dermal induction template after the removal of malignant skin cancers
      situated in various parts of the body. The participants were especially aged
      patients with multiple skin cancers, and complex clinical conditions, often
      affected by pathologies such as cardiopathy, diabetes mellitus, and
      hypercholesterolaemia, and receiving pharmacological multi-therapies,
      particularly antiplatelets and anticoagulants. In many of these patients, the
      general complex clinical picture provided significant contraindication for
      complex reconstructive surgery because of the high risk involved. All patients
      achieved complete healing about 8 weeks after the first surgery. By using a
      dermal induction template, it was possible to cover substantial loss of
      substances without the need of autologous tissue, with smoother and less apparent
      scar, minor occurrence of hypertrophic and retracted scars, better flexibility of
      healed skin and therefore a better result from an aesthetic point of view.

PMID- 24684744
TI  - The effect of statins on erectile dysfunction: a meta-analysis of randomized
      trials.
AB  - INTRODUCTION: Erectile dysfunction (ED) is common in older men, especially those
      with comorbidities such as diabetes and atherosclerotic disease, conditions where
      statins are frequently prescribed. AIM: To examine the effect of statin therapy
      on ED using the five-item version of the International Inventory of Erectile
      Function (IIEF). METHODS: We performed a random-effects meta-analysis of studies
      identified by a systematic search of MEDLINE, Web of Knowledge, the Cochrane
      Database, and ClinicalTrials.gov. Examination of the 186 retrieved citations
      resulted in the selection of 11 randomized trials for inclusion in the meta
      analysis. MAIN OUTCOME MEASURES: Change in the IIEF score. RESULTS: IIEF
      increased by 3.4 points (95% CI 1.7-5.0, P = 0.0001) with statins compared to
      control. This effect remained statistically significant after multiple
      sensitivity analyses, including analysis for publication bias, a cumulative meta
      analysis, and 11 repeated analyses with each study omitted sequentially. The
      increase in IIEF with statins was approximately one-third to one-half of that
      previously reported with phosphodiesterase-5 inhibitors and larger than the
      effect of lifestyle modification. Metaregression showed an increase in benefit
      with decreasing lipophilicity. The average age of participants and the degree of
      LDL cholesterol lowering did not alter the effect on IIEF. CONCLUSION: Statins
      cause a clinically relevant improvement of erectile function as measured by the
      five-item version of the IIEF.

PMID- 24684742
TI  - Beyond genomic variation--comparison and functional annotation of three Brassica
      rapa genomes: a turnip, a rapid cycling and a Chinese cabbage.
AB  - BACKGROUND: Brassica rapa is an economically important crop species. During its
      long breeding history, a large number of morphotypes have been generated,
      including leafy vegetables such as Chinese cabbage and pakchoi, turnip tuber
      crops and oil crops. RESULTS: To investigate the genetic variation underlying
      this morphological variation, we re-sequenced, assembled and annotated the
      genomes of two B. rapa subspecies, turnip crops (turnip) and a rapid cycling. We
      then analysed the two resulting genomes together with the Chinese cabbage Chiifu
      reference genome to obtain an impression of the B. rapa pan-genome. The number of
      genes with protein-coding changes between the three genotypes was lower than that
      among different accessions of Arabidopsis thaliana, which can be explained by the
      smaller effective population size of B. rapa due to its domestication. Based on
      orthology to a number of non-brassica species, we estimated the date of
      divergence among the three B. rapa morphotypes at approximately 250,000 YA, far
      predating Brassica domestication (5,000-10,000 YA). CONCLUSIONS: By analysing
      genes unique to turnip we found evidence for copy number differences in
      peroxidases, pointing to a role for the phenylpropanoid biosynthesis pathway in
      the generation of morphological variation. The estimated date of divergence among
      three B. rapa morphotypes implies that prior to domestication there was already
      considerably divergence among B. rapa genotypes. Our study thus provides two new
      B. rapa reference genomes, delivers a set of computer tools to analyse the
      resulting pan-genome and uses these to shed light on genetic drivers behind the
      rich morphological variation found in B. rapa.

PMID- 24684745
TI  - Strategies to calculate water binding free energies in protein-ligand complexes.
AB  - Water molecules are commonplace in protein binding pockets, where they can
      typically form a complex between the protein and a ligand or become displaced
      upon ligand binding. As a result, it is often of great interest to establish both
      the binding free energy and location of such molecules. Several approaches to
      predicting the location and affinity of water molecules to proteins have been
      proposed and utilized in the literature, although it is often unclear which
      method should be used under what circumstances. We report here a comparison
      between three such methodologies, Just Add Water Molecules (JAWS), Grand
      Canonical Monte Carlo (GCMC), and double-decoupling, in the hope of understanding
      the advantages and limitations of each method when applied to enclosed binding
      sites. As a result, we have adapted the JAWS scoring procedure, allowing the
      binding free energies of strongly bound water molecules to be calculated to a
      high degree of accuracy, requiring significantly less computational effort than
      more rigorous approaches. The combination of JAWS and GCMC offers a route to a
      rapid scheme capable of both locating and scoring water molecules for rational
      drug design. 

PMID- 24684746
TI  - Attitudes of fertile and infertile woman towards new reproductive technologies: a
      case study of Lithuania.
AB  - BACKGROUND: This article analyzes several key issues in the debate: the
      acceptability of in vitro fertilization; regulation of assisted reproduction and
      the possibilities of reimbursement for assisted reproduction treatment in
      Lithuania. METHOD: Two groups of respondents participated in the survey: fertile
      women and women with fertility disorders. 93 completed questionnaires from women
      with fertility problems and 146 from women with no fertility problems were
      analysed. RESULTS: Fertile respondents more frequently perceived the embryo as a
      human being (Fertile Individuals - 68.5%; Infertile Individuals - 35.5%; p <
      0.05) and more frequently maintained that assisted reproduction treatment should
      be only partly reimbursed (Fertile Individuals - 71.3%; Infertile Individuals -
      39.8%; p < 0.05). Respondents with fertility disorders more frequently thought
      that artificial insemination procedure could also be applied to unmarried couples
      (Fertile Individuals - 51.4%; Infertile Individuals - 76.3%; p < 0.05), and more
      frequently agreed that there should be no age limit for artificial insemination
      procedures (Fertile Individuals - 36.3%; Infertile Individuals - 67.7%; p <
      0.05). The majority of respondents in both groups (Fertile Individuals - 77.4%;
      Infertile Individuals - 82.8%; p < 0.05) believed that donation of reproductive
      cells should be regulated by law. Fertile respondents more frequently considered
      that strict legal regulation was necessary in case of the number of transferred
      embryos (Fertile Individuals - 69.2%; Infertile Individuals - 39.8%; p < 0.05)
      and freezing of embryos (Fertile Individuals - 69.9%; Infertile Individuals -
      57.0%; p < 0.05). CONCLUSION: Fertile respondents were statistically more likely
      to believe that the IVF procedure should be applied only to married couples or
      women who had a regular partner, the age limit should be defined and the
      psychological assessment of the couple's relationship and their readiness for the
      IVF procedure was necessary. In contrast, infertile couples were statistically
      more likely than fertile respondents to maintain that the IVF procedure should be
      fully reimbursed by the state. Fertile respondents were statistically more likely
      to be categorical with respect to the number of embryos and the freezing of
      embryos. Meanwhile there is a statistically significant difference in opinions of
      infertile respondents who were in favour of stricter regulation on donation of
      reproductive cells.

PMID- 24684747
TI  - Sleep duration and incidence of lung cancer in ageing men.
AB  - BACKGROUND: Previous studies have suggested an association between sleep duration
      and cancer. However, the information on sleep duration regard to risk of lung
      cancer is scanty. METHODS: Analysed data comprised prospective population-based
      cohort of 2586 men (aged 42-60 years) from Eastern Finland. Baseline survey and
      clinical examinations took place 1984-1989, and diagnosed lung cancers were
      obtained until the end of 2011 through linkage with the Finnish Cancer Registry.
      Self-reported sleep was categorized as <=6.5 h, 7-7.5 h, and >=8 h. Subjects with
      prior history of cancer or psychotropic medication (hypnotics or sedatives) were
      excluded from the analyses. Cox proportional hazards models with adjustments for
      possible confounders were used to examine the association. RESULTS: Significant
      association between sleep duration and increased lung cancer risk was observed
      after adjustments for age, examination years, cumulative smoking history, family
      cancer history and Human Population Laboratory Depression scale scores (HR 2.12,
      95% CI 1.17-3.85 for <=6.5 h sleep, and HR 1.88, 95% CI 1.09-3.22 for >=8 h
      sleep). Associations were even stronger among current smokers (HR 2.23, 95% CI
      1.14-4.34 for <=6.5 h sleep, and HR 2.09, 95% CI 1.14-3.81 for >=8 h sleep).
      After further adjustments for alcohol consumption, physical activity, body mass
      index, marital status, education years, night work, employment status, asthma and
      chronic bronchitis, the association remained significant both in the whole study
      population and among smokers. When cumulative smoking history was replaced by
      current smoking in the adjustments, the increased risk was limited to those who
      slept<6.5 h. CONCLUSIONS: Sleep duration of less than 7-7.5 hours or more than 7
      7.5 hours associates with increased lung cancer risk. The physiological factors
      underlying the association are complex, and they may relate to melatonin
      excretion patterns, low-grade inflammation in cancer development process or
      disruptions in circadian rhythmicity.

PMID- 24684748
TI  - Draft genome sequences of the type strains of Shigella flexneri held at Public
      Health England: comparison of classical phenotypic and novel molecular assays
      with whole genome sequence.
AB  - BACKGROUND: Public Health England (PHE) holds a collection of Shigella flexneri
      Type strains isolated between 1949 and 1972 representing 15 established serotypes
      and one provisional type, E1037. In this study, the genomes of all 16 PHE Type
      strains were sequenced using the Illumina HiSeq platform. The relationship
      between core genome phylogeny and serotype was examined. RESULTS: The most common
      target gene for the detection of Shigella species in clinical PCR assays, ipaH,
      was detected in all genomes. The type-specific target genes were correctly
      identified in each genome sequence. In contrast to the S. flexneri in serotype 5
      strain described by Sun et al. (2012), the two PHE serotype 5 Type strains
      possessed an additional oac gene and were differentiated by the presence
      (serotype 5b) or absence (serotype 5a) of gtrX. The somatic antigen structure and
      phylogenetic relationship were broadly congruent for strains expressing serotype
      specific antigens III, IV and V, but not for those expressing I and II. The whole
      genome phylogenies of the 15 isolates sequenced showed that the serotype 6 Type
      Strain was phylogenetically distinct from the other S. flexneri serotypes
      sequenced. The provisional serotype E1037 fell within the serotype 4 clade, being
      most closely related to the Serotype 4a Type Strain. CONCLUSIONS: The S. flexneri
      genome sequences were used to evaluate phylogenetic relationships between Type
      strains and validate genotypic and phenotypic assays. The analysis confirmed that
      the PHE S. flexneri Type strains are phenotypically and genotypically distinct.
      Novel variants will continue to be added to this archive.

PMID- 24684750
TI  - Scintigraphic Evaluation of Decontamination Lotion for Removal of Radioactive
      Contamination From Skin.
AB  - OBJECTIVE: Skin contamination is one of the most likely risks after accidental or
      occupational radiological accidents. Using scintigraphy, we assessed a topical
      lotion for its decontamination efficacy (DE) after exposure with short-lived
      medical radioisotopes technetium Tc 99m (99mTc) and thallium 201Tl (201Tl).
      METHODS: Using 99mTc (300 +/- 5 MUCi/100 MUl) and 201Tl (100 +/- 5 MUCi/100 MUl),
      the thoracoabdominal region (shaved skin) of Sprague Dawley rats and human tissue
      equivalent were contaminated and then decontaminated using cotton swabs soaked in
      formulated lotion at different time intervals. Static counts were recorded and
      calculated for DE. Histologic examination was performed on the animal model.
      RESULTS: The DE of the formulation for 99mTc and 201Tl was 85% +/- 5 and 88% +/-
      2, respectively. The prepared formulation effectively removed the radionuclides
      from the tissue surface. CONCLUSIONS: The formulated lotion assisted in the
      effective removal of radiocontaminants by decontaminating the radionuclides.
      Moreover, minimal and easily manageable radioactive waste was generated by this
      process. Further investigation regarding the infusion of formulated lotion into
      ready-to-use skin wipes for self-decontamination may be useful for mass casualty
      scenarios. (Disaster Med Public Health Preparedness. 2014;0:-).

PMID- 24684749
TI  - TMEM106B expression is reduced in Alzheimer's disease brains.
AB  - INTRODUCTION: TMEM106B is a transmembrane glycoprotein of unknown function
      located within endosome/lysosome compartments expressed ubiquitously in various
      cell types. Previously, the genome-wide association study (GWAS) identified a
      significant association of TMEM106B single nucleotide polymorphisms (SNPs) with
      development of frontotemporal lobar degeneration with ubiquitinated TAR DNA
      binding protein-43 (TDP-43)-positive inclusions (FTLD-TDP), particularly in the
      patients exhibiting the progranulin (PGRN) gene (GRN) mutations. Recent studies
      indicate that TMEM106B plays a pathological role in various neurodegenerative
      diseases, including Alzheimer's disease (AD). However, at present, the precise
      levels of TMEM106B expression in AD brains remain unknown. METHODS: By
      quantitative reverse transcription (RT)-PCR (qPCR), western blot and
      immunohistochemistry, we studied TMEM106B and PGRN expression levels in a series
      of AD and control brains, including amyotrophic lateral sclerosis, Parkinson's
      disease, multiple system atrophy and non-neurological cases. RESULTS: In AD
      brains, TMEM106B mRNA and protein levels were significantly reduced, whereas PGRN
      mRNA levels were elevated, compared with the levels in non-AD brains. In all
      brains, TMEM106B was expressed in the majority of cortical neurons, hippocampal
      neurons, and some populations of oligodendrocytes, reactive astrocytes and
      microglia with the location in the cytoplasm. In AD brains, surviving neurons
      expressed intense TMEM106B immunoreactivity, while senile plaques,
      neurofibrillary tangles and the perivascular neuropil, almost devoid of TMEM106B,
      intensely expressed PGRN. CONCLUSIONS: We found an inverse relationship between
      TMEM106B (downregulation) and PGRN (upregulation) expression levels in AD brains,
      suggesting a key role of TMEM106B in the pathological processes of AD.

PMID- 24684751
TI  - Development and evolution of vertebrate cranial placodes.

PMID- 24684752
TI  - Severity of polymorphic light eruption in pre- and post-menopausal women: a
      comparative study.
AB  - BACKGROUND: Polymorphic light eruption (PLE) is approximately four times more
      common in women than in men and often begins in young adult life. It is
      hypothesized that patients with PLE have an inherent resistance to UVL-induced
      immunosuppression, which is a physiological phenomenon in normal healthy
      individuals. Consequently, in PLE there is a delayed-type hypersensitivity
      reaction to a UVL-modified skin antigen, which results in an inflammatory
      reaction and a variable rash. The female hormone, 17beta-oestradiol, has been
      shown to inhibit UVL-induced physiological suppression of contact
      hypersensitivity responses. This has been postulated to account for the female
      preponderance of PLE. If 17beta-oestradiol plays a significant part in the
      disease, one might hypothesize that the severity of PLE might reduce in women
      after menopause. OBJECTIVES: To compare the severity of PLE in pre-menopausal
      women with that in post-menopausal women. METHODS: Eighteen pre-menopausal and 18
      post-menopausal women with PLE had their Polymorphic Light Eruption Severity
      Index (PLESI) scored by a single investigator. RESULTS: Pre-menopausal women
      (mean age 40 years; range 25-50) had a mean PLESI of 54.8 (range 0-86, SD 20.2).
      Post-menopausal women (mean age 63 years; range 53-78) had a mean PLESI of 36.8
      (range 0-74, SD 18.2). A significant difference in mean PLESI values between pre-
      and post-menopausal women was noted (18.0; 95% CI 4.9-31.0; P = 0.008). At the
      time of the study, three subjects in the pre-menopausal group and one subject in
      the post-menopausal group were on oestrogen preparations. Even after excluding
      the four patients on oral oestrogens, there remained a statistically significant
      difference in the mean PLESI scores between the pre-menopausal and post
      menopausal groups (55.10 vs. 36.64; difference of 18.46, 95% CI: 4.0-32.91; P =
      0.014). CONCLUSIONS: The severity of PLE was significantly less in post
      menopausal women as compared with pre-menopausal women.

PMID- 24684753
TI  - Construction of a high-coverage bacterial artificial chromosome library and
      comprehensive genetic linkage map of yellowtail Seriola quinqueradiata.
AB  - BACKGROUND: Japanese amberjack/yellowtail (Seriola quinqueradiata) is a commonly
      cultured marine fish in Japan. For cost effective fish production, a breeding
      program that increases commercially important traits is one of the major
      solutions. In selective breeding, information of genetic markers is useful and
      sufficient to identify individuals carrying advantageous traits but if the aim is
      to determine the genetic basis of the trait, large insert genomic DNA libraries
      are essential. In this study, toward prospective understanding of genetic basis
      of several economically important traits, we constructed a high-coverage
      bacterial artificial chromosome (BAC) library, obtained sequences from the BAC
      end, and constructed comprehensive female and male linkage maps of yellowtail
      using Simple Sequence Repeat (SSR) markers developed from the BAC-end sequences
      and a yellowtail genomic library. RESULTS: The total insert length of the BAC
      library we constructed here was estimated to be approximately 11 Gb and hence 16
      times larger than the yellowtail genome. Sequencing of the BAC-ends showed a low
      fraction of repetitive sequences comparable to that in Tetraodon and fugu. A
      total of 837 SSR markers developed here were distributed among 24 linkage groups
      spanning 1,026.70 and 1,057.83 cM with an average interval of 4.96 and 4.32 cM in
      female and male map respectively without any segregation distortion. Oxford grids
      suggested conserved synteny between yellowtail and stickleback. CONCLUSIONS: In
      addition to characteristics of yellowtail genome such as low repetitive sequences
      and conserved synteny with stickleback, our genomic and genetic resources
      constructed and revealed here will be powerful tools for the yellowtail breeding
      program and also for studies regarding the genetic basis of traits.

PMID- 24684755
TI  - Editorial: renal sympathetic denervation: a true lack of efficacy, or the victim
      of a "perfect storm"?

PMID- 24684754
TI  - Prostate tumor OVerexpressed-1 (PTOV1) down-regulates HES1 and HEY1 notch targets
      genes and promotes prostate cancer progression.
AB  - BACKGROUND: PTOV1 is an adaptor protein with functions in diverse processes,
      including gene transcription and protein translation, whose overexpression is
      associated with a higher proliferation index and tumor grade in prostate cancer
      (PC) and other neoplasms. Here we report its interaction with the Notch pathway
      and its involvement in PC progression. METHODS: Stable PTOV1 knockdown or
      overexpression were performed by lentiviral transduction. Protein interactions
      were analyzed by co-immunoprecipitation, pull-down and/or immunofluorescence.
      Endogenous gene expression was analyzed by real time RT-PCR and/or Western
      blotting. Exogenous promoter activities were studied by luciferase assays. Gene
      promoter interactions were analyzed by chromatin immunoprecipitation assays
      (ChIP). In vivo studies were performed in the Drosophila melanogaster wing, the
      SCID-Beige mouse model, and human prostate cancer tissues and metastasis. The
      Excel package was used for statistical analysis. RESULTS: Knockdown of PTOV1 in
      prostate epithelial cells and HaCaT skin keratinocytes caused the upregulation,
      and overexpression of PTOV1 the downregulation, of the Notch target genes HEY1
      and HES1, suggesting that PTOV1 counteracts Notch signaling. Under conditions of
      inactive Notch signaling, endogenous PTOV1 associated with the HEY1 and HES1
      promoters, together with components of the Notch repressor complex. Conversely,
      expression of active Notch1 provoked the dismissal of PTOV1 from these promoters.
      The antagonist role of PTOV1 on Notch activity was corroborated in the Drosophila
      melanogaster wing, where human PTOV1 exacerbated Notch deletion mutant phenotypes
      and suppressed the effects of constitutively active Notch. PTOV1 was required for
      optimal in vitro invasiveness and anchorage-independent growth of PC-3 cells,
      activities counteracted by Notch, and for their efficient growth and metastatic
      spread in vivo. In prostate tumors, the overexpression of PTOV1 was associated
      with decreased expression of HEY1 and HES1, and this correlation was significant
      in metastatic lesions. CONCLUSIONS: High levels of the adaptor protein PTOV1
      counteract the transcriptional activity of Notch. Our evidences link the pro
      oncogenic and pro-metastatic effects of PTOV1 in prostate cancer to its
      inhibitory activity on Notch signaling and are supportive of a tumor suppressor
      role of Notch in prostate cancer progression.

PMID- 24684756
TI  - The impact of live case transmission on patient outcomes during transcatheter
      aortic valve replacement: results from the VERITAS study.
AB  - BACKGROUND: Live case demonstration as an educational tool is widely used to
      rapidly and effectively disseminate information on surgical and interventional
      techniques. The risks and benefits of live case transmission for investigational
      devices, however, are in question. METHODS: Transcatheter Aortic Valve
      Intervention-Live Transmission (VERITAS) is a case-control study of 60 patients
      from 5 centers who were treated with transcatheter aortic valve replacement
      (TAVR) during live- or recorded transmission; of which 42 have matched Control
      subjects from five sites. Case and Control subjects were matched by valve type,
      access strategy (Edwards SAPIEN transfemoral, Edwards SAPIEN transapical,
      CoreValve transfemoral), Society of Thoracic Surgeons (STS) score, date of TAVR
      procedure, and primary operator. RESULTS: The Case and Control groups' baseline
      characteristics were similar, with average ages of 84 and 82 years, and STS
      scores of 6.54+/-3.22 and 6.46+/-3.20, respectively. The number of operators,
      fluoroscopy time, contrast volume and length of hospital stay were also similar
      between groups. Overall, 91.7% of the cases had TAVR via a transfemoral approach;
      72% of these patients received a closure device. The final valve position was
      adequate in 91.2% of the Case patients and in 97% of the Control patients, with
      no cases of valve migration or coronary obstruction. The Case patients had longer
      procedure times (130.2+/-50.6 versus 100.6+/-43.7min; p=0.006). The Valve
      Academic Research Consortium in-hospital complications were similar between
      groups. Four Case patients and 1 Control patient required additional valve
      implantation. CONCLUSION: Data support the notion that live transmission of TAVR
      procedures, when performed by experienced operators, can be done safely with
      similar outcomes when compared to non-transmitted cases.

PMID- 24684757
TI  - Sirolimus-eluting versus paclitaxel-eluting stents in diabetic and non-diabetic
      patients within sirolimus-eluting stent restenosis: results from the ISAR-DESIRE
      2 trial.
AB  - BACKGROUND: Concern exists relating to potential attenuated efficacy of limus
      eluting stents in patients with diabetes mellitus. In this respect diabetic
      patients with sirolimus-eluting stent (SES) failure requiring reintervention may
      be expected to derive particular benefit from a treatment-switch to paclitaxel
      eluting stent (PES) implantation. OBJECTIVE: The aim of the current report was to
      investigate outcomes of patients with SES restenosis randomized to treatment with
      SES (same stent strategy) or PES (switch stent strategy) in the pre-specified
      subgroups of patients with and without diabetes mellitus. METHODS: In the setting
      of ISAR-DESIRE 2 trial, 450 patients with clinically significant SES restenosis
      were randomly assigned to receive either SES or PES. The primary end point was in
      stent late loss at 6-8month follow-up angiography. Secondary endpoints were
      binary angiographic restenosis (diameter stenosis >50%) and target lesion
      revascularization (TLR), the composite of death or myocardial infarction (MI) and
      definite stent thrombosis at 12months. RESULTS: Of 450 patients enrolled, 162
      (36.0%) had a diagnosis of diabetes mellitus. In patients with diabetes 86
      patients were randomly assigned to SES versus 76 to PES. In patients without
      diabetes 139 were assigned to SES versus 149 to PES. Late loss was comparable
      between SES and PES both in patients with diabetes (0.38+/-0.59mm vs. 0.37+/
      0.59mm; p=0.97) and without (0.41+/-0.67mm vs. 0.38+/-0.6mm; p=0.98;
      pinteraction=0.89). Similarly binary restenosis was comparable between SES and
      PES in patients with diabetes (19.0% vs. 26.0%; p=0.32) or without (18.9% vs.
      17.8%; p=0.98; pinteraction=0.36). TLR, death or MI and definite stent thrombosis
      were also similar in SES versus PES treatment groups regardless of diabetes
      status. CONCLUSIONS: In cases of SES-restenosis, treatment with either repeat SES
      or switch to PES was associated with a comparable degree of efficacy, regardless
      of diabetic status.

PMID- 24684758
TI  - Calcification analysis by intravascular ultrasound to define a predictor of left
      circumflex narrowing after cross-over stenting for unprotected left main
      bifurcation lesions.
AB  - OBJECTIVES: The aim of this study was to identify predictors of significant LCx
      ostium compromise after distal unprotected left main coronary artery (ULMCA)
      stenting on the basis of baseline intravascular ultrasound (IVUS). BACKGROUND:
      Provisional single-stenting is considered as the default strategy for non-true
      bifurcation lesions in ULMCA. However, in certain cases, left circumflex artery
      (LCx)-ostium stenting is necessary. METHODS: A total of 77 patients underwent
      percutaneous coronary intervention with drug-eluting stents for non-true
      bifurcation lesions in ULMCA and had IVUS evaluation. Pre-procedural IVUS was
      performed to measure cross-sectional areas at the following segments: left main
      trunk, left anterior descending artery (LAD)-ostium. Post-stenting-narrowing at
      the circumflex ostium (PSN-LCx) was defined as the presence of more than 50%
      diameter stenosis at the LCx-ostium as determined by quantitative coronary
      angiography analysis. RESULTS: PSN-LCx occurred in 27 (35%) patients. The
      presence of calcified plaque at the culprit lesion as identified by IVUS was more
      frequently observed in the PSN-LCx group as compared to the non-PSN-LCx group
      (81.5% vs. 22.0%, p<0.001). Calcium arc in the PSN-LCx group was significantly
      greater than that in the non-PSN-LCx group (118.1 degrees +/-69.9 degrees  vs.
      36.9 degrees +/-63.0 degrees , p<0.001). On multivariable analysis, a calcium
      arc>60 degrees  was an independent predictor of PSN-LCx (odds ratio: 5.12, 95%
      confidence interval: 1.21-25.01, p=0.03). CONCLUSIONS: The presence of calcified
      plaque at the culprit lesion appears to be one of the factors involved in LCx
      ostial compromise in non-true bifurcation ULMCA lesions, especially when the
      calcium arc is >60 degrees .

PMID- 24684759
TI  - Drug-eluting stents in patients on chronic hemodialysis: paclitaxel-eluting
      stents vs. limus-eluting stents.
AB  - BACKGROUND: Patients requiring chronic hemodialysis (HD) are at high risk for
      restenosis after percutaneous coronary intervention (PCI) with bare metal stents.
      Outcome data on drug-eluting stent (DES) implantation in HD patients are limited
      and suggest superiority of paclitaxel-eluting stents (PES) over limus-eluting
      stents (LES). METHODS: In total, 218 consecutive patients were prospectively
      enrolled. A comparison of post-PCI outcomes up to 2 years was carried out between
      patients receiving PES (n=62) and LES (n=156; SES n=112, EES n=44). The primary
      end point was 2-year major adverse cardiac events [MACE; death, Q-wave myocardial
      infarction and target lesion revascularization (TLR)]. RESULTS: Baseline
      characteristics were comparable. The overall prevalence of diabetes mellitus was
      71%. On clinical follow-up to 2 years, MACE rates were similar [PES 32/51 (62.7%)
      vs. LES 77/132 (58.3%), p=0.59]; however, clinically-driven revascularization
      occurred more than twice as frequently in LES patients: TLR [PES 4/36 (11.1%) vs.
      LES 24/93 (25.8%), p=0.07] and target vessel revascularization [5/37 (13.5%) vs.
      33/96 (34.4%), p=0.02]. Given that overall mortality was nominally higher for PES
      patients [31/50 (62.0%) vs. 61/127 (48.0%), p=0.09], a competing outcome analysis
      was implemented for TLR against mortality, which demonstrated that the trend for
      increased TLR with LES was no longer apparent (p=0.282). On multivariable
      adjustment, only diabetes mellitus was independently associated with TLR (use of
      PES was not). CONCLUSIONS: Patients on chronic HD experience high rates of
      clinically driven TLR despite DES implantation. Use of PES does not demonstrate a
      significant advantage over LES in this population.

PMID- 24684760
TI  - Bioresorbable metal scaffold for cardiovascular application: current knowledge
      and future perspectives.
AB  - Over the last decade, the introduction of drug-eluting stents has dramatically
      reduced restenosis and the need for repeat revascularization after implantation
      of metallic stents. Numerous concerns still remain, however, because of their
      permanent nature. Thus, the concept of bioresorbable temporary scaffolds composed
      of biocompatible materials has emerged as a potential alternative to permanent
      metal stents. Here we focus on metal alloys & discuss preclinical and clinical
      experiences with bioresorbable metal scaffolds. 

PMID- 24684761
TI  - New cytotoxic cycloartane triterpene from Cassia italica aerial parts.
AB  - Phytochemical study of the aerial parts of Cassiaitalica Mill. (family: Fabaceae)
      growing in Saudi Arabia afforded one new cycloartane triterpene, named (22E)-3
      beta-hydroxycycloart-22-en-24-one (2), together with eight known compounds: beta
      sitosterol (1), uvaol (3), daucosterol (4), methyl 3,4-dihydroxybenzoate (5),
      emodin (6), 4-hydroxypheny-O-beta-D-glucopyranoside (7), aloin (8) and rutin (9).
      The structure of the isolated compounds was determined by physical, chemical and
      spectral data (UV, IR, MS, 1D ((1)H, (13)C and DEPT) and 2D ((1)H-(1)H COSY, HSQC
      and HMBC) NMR), as well as by comparing with authentic samples. Compounds 3-5 and
      7-9 were isolated for the first time from the plant. Compound 2 was evaluated for
      its cytotoxic activity against the L5178Y and PC12 cell lines. The total
      methanolic extract and compounds 5-9 exhibited free radical-scavenging activity
      using DPPH assay. 

PMID- 24684762
TI  - Copy number variations among silkworms.
AB  - BACKGROUND: Copy number variations (CNVs), which are important source for genetic
      and phenotypic variation, have been shown to be associated with disease as well
      as important QTLs, especially in domesticated animals. However, little is known
      about the CNVs in silkworm. RESULTS: In this study, we have constructed the first
      CNVs map based on genome-wide analysis of CNVs in domesticated silkworm. Using
      next-generation sequencing as well as quantitative PCR (qPCR), we identified ~319
      CNVs in total and almost half of them (~ 49%) were distributed on uncharacterized
      chromosome. The CNVs covered 10.8 Mb, which is about 2.3% of the entire silkworm
      genome. Furthermore, approximately 61% of CNVs directly overlapped with SDs in
      silkworm. The genes in CNVs are mainly related to reproduction, immunity,
      detoxification and signal recognition, which is consistent with the observations
      in mammals. CONCLUSIONS: An initial CNVs map for silkworm has been described in
      this study. And this map provides new information for genetic variations in
      silkworm. Furthermore, the silkworm CNVs may play important roles in
      reproduction, immunity, detoxification and signal recognition. This study
      provided insight into the evolution of the silkworm genome and an invaluable
      resource for insect genomics research.

PMID- 24684763
TI  - Bone mass and quality in patients with juvenile idiopathic arthritis:
      longitudinal evaluation of bone-mass determinants by using dual-energy x-ray
      absorptiometry, peripheral quantitative computed tomography, and quantitative
      ultrasonography.
AB  - INTRODUCTION: Our objective was to evaluate longitudinally the main bone-mass and
      quality predictors in young juvenile idiopathic arthritis (JIA) patients by using
      lumbar spine dual-energy X-ray absorptiometry (DXA) scan, radius peripheral
      quantitative computed tomography (pQCT), and phalangeal quantitative
      ultrasonography (QUS) at the same time. METHODS: In total, 245 patients (172
      females, 73 males; median age, 15.6 years: 148 oligoarticular, 55 polyarticular,
      20 systemic, and 22 enthesitis-related-arthritis (ERA) onset) entered the study.
      Of these, 166 patients were evaluated longitudinally. Data were compared with two
      age- and sex-matched control groups. RESULTS: In comparison with controls, JIA
      patients, but not with ERA, had a reduced spine bone-mineral apparent density
      (BMAD) standard deviation score (P < 0.001) and musculoskeletal deficits, with
      significantly lower levels of trabecular bone mineral density (TrabBMD) (P <
      0.0001), muscle cross-sectional area (CSA) (P < 0.005), and density-weighted
      polar section modulus (SSIp) (P < 0.05). In contrast, JIA showed fat CSA
      significantly higher than controls (P < 0.0001). Finally, JIA patients had a
      significant reduced amplitude-dependent speed of sound (AD-SoS) (P < 0.001), and
      QUS z score (P < 0.005). CONCLUSIONS: JIA patients have a low bone mass that,
      after a first increase due to the therapy, does not reach the normal condition
      over time. The pronounced bone deficits in JIA are greater than would be expected
      because of reduction in muscle cross-sectional area. Thus, bone alterations in
      JIA likely represent a mixed defect of bone accrual and lower muscle forces.

PMID- 24684764
TI  - The electronic cigarette. Official statement of the Spanish Society of Pneumology
      and Thoracic Surgery (SEPAR) on the efficacy, safety and regulation of electronic
      cigarettes.
AB  - The electronic cigarette (EC) is a device formed by three basic elements:
      battery, atomizer and cartridge. When assembled, it looks like a cigarette. The
      cartridge contains different substances: propylene glycol, glycerine and,
      sometimes, nicotine. When the user "vapes", the battery is activated, the
      atomizer is heated and the liquid is drawn in and vaporized. The smoker inhales
      the mist produced. Various substances have been detected in this mist:
      formaldehyde, acetaldehyde and acrolein and some heavy metals. Although these are
      found in lower concentrations than in cigarettes, they may still be harmful for
      the human body. Several surveys show that 3-10% of smokers regularly use e
      cigarettes. A randomized study has shown that the efficacy of e-cigarettes for
      helping smokers to quit is similar to nicotine patches. Nevertheless, the study
      has relevant methodological limitations and reliable conclusions cannot be
      deduced. This report sets down the Position Statement of the Spanish Society of
      Pulmonology and Thoracic Surgery (SEPAR) on the efficacy and safety of e
      cigarettes. This statement declares that e-cigarettes should be regulated as
      medicinal products. 

PMID- 24684765
TI  - An uncommon intrafissural mass: pleural primitive neuroectodermal tumor.

PMID- 24684766
TI  - Anthracosis in a Coptic mummy.

PMID- 24684767
TI  - Development, validation and comparison of two nomograms predicting prostate
      cancer at initial 12-core biopsy.
AB  - AIM: Our aim was to establish, validate and compare two nomograms in an Iranian
      population for the first time using clinical, laboratory and transrectal
      ultrasonography (TRUS) findings for predicting prostate cancer at initial biopsy.
      METHODS: Data were collected on a total of 916 men referred for an initial
      prostate biopsy in our center in a 7-year period. Variables analyzed included
      age, prostate-specific antigen (PSA), free/total PSA (%fPSA), digital rectal
      examination (DRE) findings, prostate volume (PV) and presence of hypoechoic
      lesion on TRUS. Univariate logistic regression models were fitted to test cancer
      predictors. Two multivariate logistic regression models were fitted to create
      nomograms. Both models were internally validated. Calibration of nomograms was
      assessed graphically. The area under the receiver operating characteristic curve
      (AUC) was calculated as a scale of discrimination and predictive accuracy and
      also used to compare models. RESULTS: Prostate cancer was detected in 221/669
      (33%) men. Based on univariate logistic regression, all of variables except DRE
      were significant predictors of prostate cancer, with highest AUC for PV (AUC
      0.696, 95% CI 0.653-0.738).AUC of nomogram with and without TRUS findings and PSA
      alone were 0.791, 0.721 and 0.624, respectively. In internal validation, both
      nomograms had acceptable calibration plots. CONCLUSION: Our nomogram based on
      age, DRE, PSA, %fPSA and TRUS finding was significantly more accurate in
      predicting initial prostate biopsy outcome in men.

PMID- 24684768
TI  - Integration of lectin-glycan recognition systems and immune cell networks in CNS
      inflammation.
AB  - Multiple sclerosis (MS) is a progressive degenerative disorder of the central
      nervous system (CNS), characterized by inflammation, demyelination and axonal
      loss. While the majority of MS patients experience relapsing-remitting symptoms
      followed by a secondary progressive phase, about 10-15% patients exhibit a
      primary progressive disease involving continuous progression from its onset. Here
      we review the role of lectin-glycan recognition systems, including those
      concerning siglecs, C-type lectins and galectins in the pathogenesis of MS and
      experimental autoimmune encephalomyelitis. Particularly, we will focus on the
      role of galectins in the fate of T cells, dendritic cells and CNS cell
      populations. Understanding the regulatory circuits governed by lectin-glycan
      interactions and their association with disease-associated cytokine networks will
      contribute to develop novel therapeutic strategies in MS. 

PMID- 24684770
TI  - Discussion.

PMID- 24684769
TI  - Elective endovascular aortic repair conversion for type Ia endoleak is not
      associated with increased morbidity or mortality compared with primary juxtarenal
      aneurysm repair.
AB  - OBJECTIVE: Type Ia endoleak after endovascular aortic repair (EVAR) can be a
      challenging complication to manage, and due to concerns regarding morbidity and
      mortality of open surgical conversion (OSC), reports of complex endoluminal
      salvage techniques are increasing. Despite development of these endovascular
      remedial strategies, many patients ultimately require OSC. The purpose of this
      analysis was to outcomes of elective OSC for type Ia endoleak and compare them
      with elective primary open juxtarenal aneurysm repair (OJAR) to determine if
      these concerns are warranted. METHODS: From 2000 to 2012, 54 patients underwent
      EVAR OSC at median time of 27 months (interquartile range, 9-55 months).
      Indications included endograft thrombosis in 2 (4%), intraoperative EVAR failure
      in 3 (6%), rupture in 5 (9%), graft infection in 6 (11%), and type Ia endoleak in
      25 (all: 38 [70%]). Because many OSCs are performed for emergency indications
      without endovascular options, we chose elective type Ia endoleak patients as our
      study group. These 25 patients were compared with an elective OJAR cohort matched
      by anatomy and comorbidities. Primary end points were 30-day and 1-year
      mortality. Secondary end points included early complications, cross-clamp time,
      procedure time, blood loss, and length of stay. RESULTS: Demographic and
      comorbidity data in the OSC and OJAR groups did not differ, with the exception
      that OJAR patients presented with smaller aneurysm diameter and a higher rate of
      chronic obstructive pulmonary disease (P = .03). OSC patients more frequently
      underwent a nontube graft repair (OSC, n = 20 [80%] vs OJAR, n = 6 [24%]; P =
      .0002), required longer procedure times (P = .03), and received more plasma
      transfusions (P = .03). The 30-day mortality was 4% in both groups (observed
      difference in rates, 0%; 95% confidence interval for difference in mortality
      rates, -14.0% to 14.0%; P = 1). A similar rate of major complications occurred
      (OSC, n = 9 [36%] vs OJAR, n = 8 [32%]; P = 1). One-year survival was 83% in OSC
      and 91% in OJAR (observed difference, 7%; 95% confidence interval, -15% to 29%; P
      = .65). CONCLUSIONS: Despite many advances in EVAR technology, the need for OSC
      persists and will likely become more common as older-generation devices fail or
      providers attempt EVAR in more anatomically complex patients. Elective OSC for
      type Ia endoleak can be technically challenging but is not associated with
      increased morbidity or mortality compared with OJAR in appropriately selected
      patients. These results should be considered before pursuing complex endovascular
      remediation of EVAR failures.

PMID- 24684771
TI  - Human type I pancreatic elastase treatment of arteriovenous fistulas in patients
      with chronic kidney disease.
AB  - OBJECTIVE: This study explored the safety and efficacy of recombinant type I
      pancreatic elastase (PRT-201) topically applied once to the external surface of
      an arteriovenous fistula. METHODS: This was a randomized, double-blind, placebo
      controlled trial. Adults with kidney disease undergoing creation of a
      radiocephalic fistula (RCF) or brachiocephalic fistula were randomized to
      treatment with placebo (n = 51), PRT-201 at 10 MUg (n = 51), or PRT-201 at 30 MUg
      (n = 49). The primary efficacy measure was unassisted primary patency (PP) over 1
      year. Secondary efficacy measures were secondary patency (SP), unassisted
      maturation by ultrasound interrogation, use for hemodialysis, and hemodynamically
      significant lumen stenosis. RESULTS: Median PP was 224 days for placebo and >365
      days for the PRT-201 groups. At 1 year, 45%, 54%, and 53% of placebo, 10-MUg, and
      30-MUg patients retained PP. The risk of PP loss was nonsignificantly reduced for
      10 MUg (hazard ratio [HR], 0.69; P = .19) and 30 MUg (HR, 0.67; P = .17) vs
      placebo. In the subset (44% of patients) with a RCF, the median PP was 125 days
      for placebo and >365 days for the PRT-201 groups. At 1 year, 31%, 50%, and 63% of
      placebo, 10-MUg, and 30-MUg RCFs retained PP. The risk of RCF PP loss was
      nonsignificantly reduced by 10 MUg (HR, 0.59; P = .18) and significantly reduced
      by 30 MUg (HR, 0.37; P = .02) vs placebo. At 1 year, 77%, 81%, and 83% of
      placebo, 10-MUg, and 30-MUg patients retained SP. The risk of SP loss was
      nonsignificantly reduced for 10 MUg (HR, 0.79; P = .61) and 30 MUg (HR, 0.76; P =
      .55) vs placebo. In the subset with RCFs, 65%, 82%, and 90% of placebo, 10-MUg,
      and 30-MUg patients retained SP at 1 year. The risk of RCF SP loss was
      nonsignificantly reduced for 10 MUg (HR, 0.45; P = .19) and 30 MUg (HR, 0.27; P =
      .08) vs placebo. At month 3, 67%, 87% (P = .03), and 92% (P < .01) of the
      placebo, 10-MUg, and 30-MUg group fistulas had unassisted maturation by
      ultrasound interrogation. At month 3 in the subset with an RCF, 47%, 74% (P =
      .17), and 93% (P < .01) of placebo, 10-MUg, and 30-MUg group fistulas had
      unassisted maturation by ultrasound interrogation. Adverse event reports were not
      meaningfully different between groups. CONCLUSIONS: PRT-201 appeared safe. The
      primary efficacy end point was not met. However, both PRT-201 doses were
      associated with improved unassisted maturation. The 30-MUg dose was associated
      with increased PP in the subset with RCF.

PMID- 24684772
TI  - Retention in care, resource utilization, and costs for adults receiving
      antiretroviral therapy in Zambia: a retrospective cohort study.
AB  - BACKGROUND: Of the estimated 800,000 adults living with HIV in Zambia in 2011,
      roughly half were receiving antiretroviral therapy (ART). As treatment scale up
      continues, information on the care provided to patients after initiating ART can
      help guide decision-making. We estimated retention in care, the quantity of
      resources utilized, and costs for a retrospective cohort of adults initiating ART
      under routine clinical conditions in Zambia. METHODS: Data on resource
      utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient
      clinic visits, and fixed resources) and retention in care were extracted from
      medical records for 846 patients who initiated ART at >=15 years of age at six
      treatment sites between July 2007 and October 2008. Unit costs were estimated
      from the provider's perspective using site- and country-level data and are
      reported in 2011 USD. RESULTS: Patients initiated ART at a median CD4 cell count
      of 145 cells/MUL. Fifty-nine percent of patients initiated on a tenofovir
      containing regimen, ranging from 15% to 86% depending on site. One year after ART
      initiation, 75% of patients were retained in care. The average cost per patient
      retained in care one year after ART initiation was $243 (95% CI, $194-$293),
      ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on
      site. Patients retained in care one year after ART initiation received, on
      average, 11.4 months' worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry
      tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or
      clinical officer. At all sites, ARV drugs were the largest cost component,
      ranging from 38% to 84% of total costs, depending on site. CONCLUSIONS: Patients
      initiate ART late in the course of disease progression and a large proportion
      drop out of care after initiation. The quantity of resources utilized and costs
      vary widely by site, and patients utilize a different mix of resources under
      routine clinical conditions than if they were receiving fully guideline
      concordant care. Improving retention in care and guideline concordance, including
      increasing the use of tenofovir in first-line ART regimens, may lead to increases
      in overall treatment costs.

PMID- 24684773
TI  - Occupational consequences after isolated reconstruction of the insufficient
      posterior cruciate ligament.
AB  - BACKGROUND: With incorrect or even without treatment, acute injuries of the
      posterior cruciate ligament (PCL) can lead to chronic instability of the knee
      joint. After delayed treatment, negative occupational changes and reduced quality
      of life can occur. These aspects have not yet been investigated. The purpose of
      this study was to evaluate occupational consequences after isolated
      reconstruction in cases of chronic PCL insufficiency. FINDINGS: 12 patients
      treated with PCL reconstruction in a single bundle technique, using hamstring
      tendon grafts, were evaluated. All patients were operated upon at least 3 months
      after injury. Mean time of follow-up was 51 +/- 18.2 months (14-75). Radiological
      assessment (Telos stress device) showed a side comparison of total translation of
      4.5 +/- 2.6 mm. Occupational consequences have been evaluated by the
      classification system "REFA". Median time incapacity for work was 8 weeks. Nearly
      all patients achieved the mental status of the normal population (SF-36), but
      physical status was still restricted. A pre- to postoperative improvement of the
      clinical scores could be seen: Lysholm-Score: 46.4 +/- 17.3 to 84.7 +/- 14.1, HSS
      Score: 74.3 +/- 10.5 to 88.3 +/- 10.7. Postoperative evaluated scores were:
      Tegner score: 4.8 +/- 1.2, IKDC score: 80.0 +/- 16.2, VPS: 3.4 +/- 2.7. Patients
      with low physical load in their workplace described significantly better clinical
      results in every clinical score (p < .05) and less pain than patients with high
      physical load prior to the accident (VPS: REFA < 2: 2.4 +/- 2.6, REFA >= 2: 5.5
      +/- 1.7; p < 0.05). CONCLUSIONS: Operative treated patients with a chronic PCL
      insufficiency achieve an improvement of the clinical result. Patients with low
      physical load at their workplace achieve less restrictions.

PMID- 24684774
TI  - Cost implications of the use of basal insulin glargine in people with early
      dysglycemia: the ORIGIN trial.
AB  - AIMS: The cost implications of the Outcome Reduction with an Initial Glargine
      Intervention (ORIGIN) trial were evaluated using a prespecified analysis plan.
      METHODS: Purchasing power parity-adjusted country-specific costs were applied to
      consumed healthcare resources by participants from each country. Subgroup
      analyses were conducted on subgroups based on baseline metabolic status and
      diabetes duration. RESULTS: The total undiscounted cost per participant in the
      insulin glargine arm was $13,491 ($13,080 to $14,254) versus $11,189 ($10,568 to
      $12,147) for standard care, an increase of $2303 ($1370 to $3235; p < 0.0001);
      the discounted increase was $2099 ($1276 to $2923; P < 0.0001). The greater
      number of mainly generic oral anti-diabetic agents in the standard group
      partially offset the higher cost of basal insulin glargine. As the trial
      progressed and the standard group required more anti-diabetic medications, the
      annual cost difference decreased, reaching $68 (-$160 to $295) in the last year.
      The subgroup whose baseline diabetes duration was >= 6 years achieved cost
      savings during the trial. CONCLUSIONS: From a global perspective basal insulin
      glargine use in ORIGIN incurred greater costs than standard care using older
      generic drugs. Nevertheless, the cost difference fell with time such that the
      intervention was cost-neutral by the last year.

PMID- 24684775
TI  - Acute pancreatitis during pregnancy, 7-year experience of a tertiary referral
      center.
AB  - INTRODUCTION: Acute pancreatitis is a common cause of acute abdomen in pregnant
      women. The purpose of this study was to determine the frequency at our
      institution and its management and outcomes. METHODS: A retrospective analysis of
      a database of cases presented in 7 consecutive years at a tertiary center was
      performed. RESULTS: Between December 2002 and August 2009, there were 19 cases of
      acute pancreatitis in pregnant women, 85% with a biliary etiology. The highest
      frequency was in the third trimester of pregnancy (62.5% cases). In cases of
      gallstone pancreatitis, 43.6% of pregnant women had had previous episodes before
      pregnancy. A total of 52.6% of the patients were readmitted for a recurrent
      episode of pancreatitis during their pregnancy. Overall, 26.3% of the patients
      received antibiotic treatment and 26.3% parenteral nutrition. Laparoscopic
      cholecystectomy was performed during the 2nd trimester in two patients (10.5%).
      There was no significant maternal morbidity. CONCLUSION: Acute pancreatitis in
      pregnant women usually has a benign course with proper treatment. In cases of
      biliary origin, it appears that a surgical approach is suitable during the second
      trimester of pregnancy.

PMID- 24684776
TI  - Medical tongue piercing - development and evaluation of a surgical protocol and
      the perception of procedural discomfort of the participants.
AB  - BACKGROUND: A system providing disabled persons with control of various assistive
      devices with the tongue has been developed at Aalborg University in Denmark. The
      system requires an activation unit attached to the tongue with a small piercing.
      The aim of this study was to establish and evaluate a safe and tolerable
      procedure for medical tongue piercing and to evaluate the expected and perceived
      procedural discomfort. METHODS: Four tetraplegic subjects volunteered for the
      study. A surgical protocol for a safe insertion of a tongue barbell piercing was
      presented using sterilized instruments and piercing parts. Moreover, post
      procedural observations of participant complications such as bleeding, edema, and
      infection were recorded. Finally, procedural discomforts were monitored by VAS
      scores of pain, changes in taste and speech as well as problems related to
      hitting the teeth. RESULTS: The piercings were all successfully inserted in less
      than 5 min and the pain level was moderate compared with oral injections. No
      bleeding, infection, embedding of the piercing, or tooth/gingival injuries were
      encountered; a moderate edema was found in one case without affecting the speech.
      In two cases the piercing rod later had to be replaced by a shorter rod, because
      participants complained that the rod hit their teeth. The replacements prevented
      further problems. Moreover, loosening of balls was encountered, which could be
      prevented with the addition of dental glue. No cases of swallowing or aspiration
      of the piercing parts were recorded. CONCLUSIONS: The procedure proved simple,
      fast, and safe for insertion of tongue piercings for tetraplegic subjects in a
      clinical setting. The procedure represented several precautions in order to avoid
      risks in these susceptible participants with possible co-morbidity. No serious
      complications were encountered, and the procedure was found tolerable to the
      participants. The procedure may be used in future studies with tongue piercings
      being a prerequisite for similar systems, and this may include insertion in an
      out-patient setting.

PMID- 24684777
TI  - Rheumatoid forefoot reconstruction: outcome of 1st metatarsophalangeal joint
      fusion and the Stainsby procedure in the lesser toes.
AB  - BACKGROUND: Rheumatoid arthritis is a chronic inflammatory disease involving
      connective tissue and joints. The most common rheumatoid forefoot deformities are
      hallux valgus and clawed lesser toes. There are a number of surgical procedures
      that have been described offering symptomatic relief and anatomical correction.
      OBJECTIVES: This prospective case series aims to assess outcome in patients with
      rheumatoid forefoot deformities who underwent a novel combination of 1st
      metatarsophalangeal joint fusions and Stainsby procedures. METHODS: Thirteen
      procedures were performed on 12 consecutive patients with an age range of 55-71
      (mean=62) between 02/2009 and 05/2011. AOFAS scoring was performed preoperatively
      and again six and 12 months post-surgery. Hallux valgus (HVA) and intermetatarsal
      angles (IMA) were measured preoperatively and six weeks and six months
      postoperatively. RESULTS: The mean AOFAS score increased from 46 to 72, 12 months
      postoperatively. The mean HVA reduced from 48 degrees  preoperatively to 14
      degrees  six months postoperatively. The IMA decreased from 15 degrees  to 10
      degrees  six months postoperatively. CONCLUSIONS: The novel approach of 1st
      metatarsophalangeal fusion combined with lesser toe metatarsal head sparing is an
      effective procedure that reduces forefoot deformity and pain.

PMID- 24684778
TI  - Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and
      mechanistic in vitro studies.
AB  - BACKGROUND: Porphyrin TMPyP4 (P4) and its C14H28-alkyl derivative (C14) are G
      quadruplex binders and singlet oxygen (1O2) generators. In contrast, TMPyP2 (P2)
      produces 1O2 but it is not a G-quadruplex binder. As their photosensitizing
      activity is currently undefined, we report in this study their efficacy against a
      melanoma skin tumour and describe an in vitro mechanistic study which gives
      insights into their anticancer activity. METHODS: Uptake and antiproliferative
      activity of photoactivated P2, P4 and C14 have been investigated in murine
      melanoma B78-H1 cells by FACS, clonogenic and migration assays. Apoptosis was
      investigated by PARP-1 cleavage and annexin-propidium iodide assays.
      Biodistribution and in vivo anticancer activity were tested in melanoma tumour
      bearing mice. Porphyrin binding and photocleavage of G-rich mRNA regions were
      investigated by electrophoresis and RT-PCR. Porphyrin effect on ERK pathway was
      explored by Western blots. RESULTS: Thanks to its higher lipophylicity C14 was
      taken up by murine melanoma B78-H1 cells up to 30-fold more efficiently than P4.
      When photoactivated (7.2 J/cm2) in B78-H1 melanoma cells, P4 and C14, but not
      control P2, caused a strong inhibition of metabolic activity, clonogenic growth
      and cell migration. Biodistribution studies on melanoma tumour-bearing mice
      showed that P4 and C14 localize in the tumour. Upon irradiation (660 nm, 193
      J/cm2), P4 and C14 retarded tumour growth and increased the median survival time
      of the treated mice by ~50% (P <0.01 by ANOVA), whereas porphyrin P2 did not. The
      light-dependent mechanism mediated by P4 and C14 is likely due to the binding to
      and photocleavage of G-rich quadruplex-forming sequences within the 5'
      untranslated regions of the mitogenic ras genes. This causes a decrease of RAS
      protein and inhibition of downstream ERK pathway, which stimulates proliferation.
      Annexin V/propidium iodide and PARP-1 cleavage assays showed that the porphyrins
      arrested tumour growth by apoptosis and necrosis. C14 also showed an intrinsic
      light-independent anticancer activity, as recently reported for G4-RNA binders.
      CONCLUSIONS: Porphyrins P4 and C14 impair the clonogenic growth and migration of
      B78-H1 melanoma cells and inhibit melanoma tumour growth in vivo. Evidence is
      provided that C14 acts through light-dependent (mRNA photocleavage) and light
      independent (translation inhibition) mechanisms.

PMID- 24684779
TI  - Synergistic anti-inflammatory effect: simvastatin and pioglitazone reduce
      inflammatory markers of plasma and epicardial adipose tissue of coronary patients
      with metabolic syndrome.
AB  - BACKGROUND: The inappropriate secretion of adipocytokines plays a critical role
      in chronic inflammatory states associated with obesity-linked type 2 diabetes and
      atherosclerosis. The pleiotropic actions of simvastatin and pioglitazone on
      epicardial adipose tissue (EAT) are unknown. This study assessed the anti
      inflammatory actions of simvastatin and pioglitazone on EAT in patients with
      coronary artery disease (CAD) and metabolic syndrome (MS). METHODS: A total of 73
      patients with multivessel CAD who underwent elective bypass grafting were non
      randomly allocated to one of four subgroups: Control (n = 17), simvastatin (20
      mg/day, n = 20), pioglitazone (15 mg or 30 mg/day, n = 18), or simvastatin +
      pioglitazone (20 mg/day + 30 mg/day, respectively, n = 18); 20 valvar patients
      were also included. EAT samples were obtained during surgery. The infiltration of
      macrophages and lymphocytes and cytokines secretion were investigated using
      immunohistochemical staining and compared to plasma inflammatory biomarkers.
      RESULTS: Simvastatin significantly reduced plasma interleukin-6, leptin, resistin
      and monocyte chemoattractant protein-1 (p < 0.001 for all); pioglitazone reduced
      interleukin-6, tumoral necrose factor-alpha, resistin and matrix
      metalloproteinase-9 (p < 0.001 for all). Simvastatin + pioglitazone treatment
      further reduced plasmatic variables, including interleukin-6, tumoral necrose
      factor-alpha, resistin, asymmetric dimethylarginine and metalloproteinase-9 vs.
      the control group (p < 0.001). Higher plasma adiponectin and lower high
      sensitivity C-reactive protein concentrations were found simultaneously in the
      combined treatment group. A positive correlation between the mean percentage
      systemic and tissue cytokines was observed after treatments. T- and B-lymphocytes
      and macrophages clusters were observed in the fat fragments of patients treated
      with simvastatin for the first time. CONCLUSIONS: Pioglitazone, simvastatin or
      combination treatment substantially reduced EAT and plasma inflammatory markers
      in CAD and MS patients. These tissue effects may contribute to the control of
      coronary atherosclerosis progression.

PMID- 24684780
TI  - Impact of prior admissions on 30-day readmissions in medicare heart failure
      inpatients.
AB  - OBJECTIVE: To determine how all-cause hospitalizations within 12 months preceding
      an index heart failure (HF) hospitalization affect risk stratification for 30-day
      all-cause readmission. PATIENTS AND METHODS: Early readmission of inpatients with
      HF is challenging to predict, yet this outcome is used to compare hospital
      performance and guide reimbursement. Most risk models do not consider the
      potentially important variable of prior admissions. We analyzed Medicare
      inpatients with HF aged 66 years or older admitted to 14 Michigan community
      hospitals from October 1, 2002, to March 31, 2003, and from January 1 to June 30,
      2004. Clinical data were obtained from admission charts, hospitalization dates
      from Centers for Medicare & Medicaid Services (CMS) claims, and mortality dates
      from the Social Security Death Index. We used mixed-effects logistic regression
      and reclassification indices to evaluate the ability of a CMS chart-based
      readmission risk model, prior admissions, and their combination to predict 30-day
      readmission in survivors of the index HF hospitalization. RESULTS: Of 1807
      patients, 43 (2.4%) died during the index admission; 476 of 1764 survivors (27%)
      were readmitted 30 or fewer days after discharge. Adjusted for the CMS
      readmission model, prior admissions significantly increased the odds of 30-day
      readmission (1 vs 0: odds ratio, 4.67; 95% CI, 3.37-6.46; >=2 vs 0: odds ratio,
      6.49; 95% CI, 4.93-8.55; both P<.001), improved model discrimination (c
      statistic, 0.61-0.74, P<.001), and reclassified many patients (net
      reclassification index, 0.40; integrated discrimination index, 0.12). CONCLUSION:
      In Medicare inpatients with HF, prior all-cause admissions strongly increase all
      cause readmission risk and markedly improve risk stratification for 30-day
      readmission.

PMID- 24684781
TI  - Contemporary strategies in the diagnosis and management of heart failure.
AB  - Heart failure (HF) is an important public health problem, and strategies are
      needed to improve outcomes and decrease health care resource utilization and
      costs. Its prevalence has increased as the population ages, and HF continues to
      be associated with a high mortality rate and frequent need for hospitalization.
      The total cost of care for patients with HF was $30.7 billion in 2012, and it is
      estimated to more than double to $69.8 billion by 2030. Given this reality, there
      has been recent investigation into ways of identifying and preventing HF in
      patients at risk (stage A HF) and those with cardiac structural and functional
      abnormalities but no clinical HF symptoms (stage B). For patients who have
      symptoms of HF (stage C), there has been important research into the most
      effective ways to decongest patients hospitalized with acute decompensated HF and
      prevent future hospital readmissions. Successful strategies to treat patients
      with HF and preserved ejection fraction, which has increased in prevalence,
      continue to be sought. We are in the midst of a rapid evolution in our ability to
      care for patients with end-stage HF (stage D) because of the introduction of and
      improvements in mechanical circulatory support. Left ventricular assist devices
      used as destination therapy offer an important therapeutic option to patients who
      do not qualify for heart transplant because of advanced age or excessive
      comorbidity. This review provides a thorough update on contemporary strategies in
      the diagnosis and management of HF by stage (A to D) that have emerged during the
      past several years. 

PMID- 24684782
TI  - Long-term use of zolpidem increases the risk of major injury: a population-based
      cohort study.
AB  - OBJECTIVE: To estimate the risk of head injury or fracture requiring
      hospitalization in patients treated with zolpidem. PATIENTS AND METHODS: We
      identified 8188 patients 18 years and older who had received a first prescription
      for zolpidem between January 1, 2000, and December 31, 2009, and compared them
      with 32,752 age- and sex-matched patients who had not used sedative-hypnotic
      agents. Both cohorts were followed up for at least 1 year or until
      hospitalization for head injury or fracture (major injury). Hazard ratios (HRs)
      and 95% CIs were calculated by comparing the incidence of major injury requiring
      hospitalization between the zolpidem user and comparison cohorts, including age
      groups 18 to 54 and 55 years or more, using a Cox proportional hazards regression
      analysis. RESULTS: The adjusted HR for major injury in zolpidem users was 1.67
      (95% CI, 1.19-2.34). The adjusted HR for major injury in zolpidem users in the
      younger cohort (aged 18-54 years) was 1.70 (95% CI, 1.15-2.51) and in the older
      cohort (aged >=55 years) was 1.57 (95% CI, 0.78-3.13). The adjusted HR for major
      injury in zolpidem users increased when the zolpidem dosage increased (HR, 2.04;
      95% CI, 1.32-3.13 for 71-800 mg/y; HR, 4.37; 95% CI, 2.12-9.01 for 801-1600 mg/y;
      and HR, 4.74; 95% CI, 2.38-9.42 for >1600 mg/y). CONCLUSION: The long-term use of
      zolpidem is associated with a significantly greater risk of head injury or
      fracture requiring hospitalization than in patients who do not use sedative
      hypnotic agents (P<.001), particularly in the younger (aged 18-54 years)
      patients.

PMID- 24684784
TI  - Perceptions and experiences of people with mental illness regarding their
      interactions with police.
AB  - This study examined the perceptions and lived experiences of people with mental
      illness in relation to their interactions with the police. A community-based
      participatory research approach was used and a procedural justice theoretical
      perspective guided the study. In-depth, semi-structured interviews were conducted
      by peer researchers with 60 people with mental illness who had interacted with
      the police and were living in Metro Vancouver, Canada. Among the study
      participants, contact with the police was frequent and occurred under a diverse
      range of circumstances. The majority of participants perceived being treated in a
      procedurally just manner by the police officer(s) who were involved in their most
      recent interaction. Almost three-quarters (n=43, 72%) of participants were
      generally satisfied with how the police officer(s) had handled their most recent
      interaction. The slight majority of participants (n=30, 51%) rated their previous
      contacts with the police as a positive experience overall, with 32% (n=19)
      indicating that their previous interactions with the police were negative life
      experiences. The findings paint a more balanced picture than that which is often
      portrayed by the media. Emphasizing a procedural justice framework for police
      handling of situations involving people with mental illness is a vital step
      toward improving how these interactions are experienced and perceived. 

PMID- 24684783
TI  - Diagnostic capability of comprehensive handheld vs transthoracic
      echocardiography.
AB  - OBJECTIVE: To assess the diagnostic capability of handheld echocardiography (HHE)
      compared with transthoracic echocardiography (TTE) performed and evaluated by
      experienced sonographers and expert echocardiographers. PATIENTS AND METHODS: We
      conducted a prospective study of adult outpatients undergoing comprehensive TTE
      between July 9, 2012, and April 3, 2013. Experienced sonographers performed a
      detailed, standardized examination using a handheld ultrasound device that
      included 2-dimensional and color Doppler images from standard imaging windows.
      Images from TTE and HHE were independently interpreted by expert
      echocardiographers to whom the other study was masked. Agreement between the
      standard TTE and the HHE reports was analyzed. RESULTS: The study group contained
      190 patients (mean +/- SD age, 62 +/- 17 years; 49% male [n=93]). The kappa
      values were 0.52 for left ventricular (LV) enlargement, 0.52 for right
      ventricular enlargement, 0.62 for regional wall motion abnormalities, 0.73 for
      aortic stenosis, and 0.61 for mitral regurgitation. Lin concordance correlation
      coefficients ranged from 0.89 for LV end-systolic diameter to 0.78 for LV end
      diastolic diameter. In 51 patients (27%), echocardiographic findings were
      discordant between HHE and standard TTE. The most common discordant finding was
      the presence vs absence of any regional wall motion abnormalities. In discordant
      cases, HHE tended to underestimate, rather than overestimate, the severity of
      abnormal findings. CONCLUSION: In experienced hands, HHE shows moderate
      correlation with standard TTE, but discordant findings were present in 27% of
      patients. Even when performed and interpreted by experienced operators, HHE
      should not be used as a surrogate for standard TTE. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01558518.

PMID- 24684785
TI  - Phase 2 trial of everolimus and carboplatin combination in patients with triple
      negative metastatic breast cancer.
AB  - INTRODUCTION: Rapamycin acts synergistically with platinum agents to induce
      apoptosis and inhibit proliferation in breast cancer cell lines. Combination of
      everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR)
      inhibitor) and carboplatin may have activity in metastatic triple-negative breast
      cancer (TNBC). METHODS: The primary objective of this study was to determine
      clinical benefit rate (CBR), that is (complete remission (CR) + partial remission
      (PR) + stable disease (SD) lasting >=6 months) and the toxicity of
      everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was
      allowed. Treatment consisted of intravenous carboplatin area under the curve
      (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with
      daily 5 mg everolimus. RESULTS: We enrolled 25 patients in this study. Median age
      was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of
      disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was
      achieved in a patient progressing on single agent carboplatin. The median
      progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and
      overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There
      were seven patients (28%) with >= grade 3 thrombocytopenia; three (12%) with
      grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3
      anemia. Greater hematological toxicity was seen in the first seven patients
      treated with carboplatin AUC5/6. After the amendment for starting dose of
      carboplatin to AUC 4, the regimen was well tolerated with only one out of 18
      patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia.
      There was only one case of mucositis. CONCLUSION: Everolimus-carboplatin was
      efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed
      when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC
      4 was well tolerated in combination with everolimus with continuing responses.
      TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01127763.

PMID- 24684786
TI  - Implications of human genome structural heterogeneity: functionally related genes
      tend to reside in organizationally similar genomic regions.
AB  - BACKGROUND: In an earlier study, we hypothesized that genomic segments with
      different sequence organization patterns (OPs) might display functional
      specificity despite their similar GC content. Here we tested this hypothesis by
      dividing the human genome into 100 kb segments, classifying these segments into
      five compositional groups according to GC content, and then characterizing each
      segment within the five groups by oligonucleotide counting (k-mer analysis; also
      referred to as compositional spectrum analysis, or CSA), to examine the
      distribution of sequence OPs in the segments. We performed the CSA on the entire
      DNA, i.e., its coding and non-coding parts the latter being much more abundant in
      the genome than the former. RESULTS: We identified 38 OP-type clusters of
      segments that differ in their compositional spectrum (CS) organization. Many of
      the segments that shared the same OP type were enriched with genes related to the
      same biological processes (developmental, signaling, etc.), components of
      biochemical complexes, or organelles. Thirteen OP-type clusters showed
      significant enrichment in genes connected to specific gene-ontology terms. Some
      of these clusters seemed to reflect certain events during periods of horizontal
      gene transfer and genome expansion, and subsequent evolution of genomic regions
      requiring coordinated regulation. CONCLUSIONS: There may be a tendency for genes
      that are involved in the same biological process, complex or organelle to use the
      same OP, even at a distance of ~ 100 kb from the genes. Although the intergenic
      DNA is non-coding, the general pattern of sequence organization (e.g., reflected
      in over-represented oligonucleotide "words") may be important and were protected,
      to some extent, in the course of evolution.

PMID- 24684787
TI  - Brain lipidomes of subcortical ischemic vascular dementia and mixed dementia.
AB  - Despite its importance as the leading cause of vascular dementia, the primary
      pathogenic mechanisms in subcortical ischemic vascular dementia (SIVD) have
      remained elusive. Because of the lack of approved therapeutic agents for SIVD,
      there is a pressing need to identify novel therapeutic targets. Comparative
      lipidomic analyses of SIVD and mixed dementia (i.e., SIVD and Alzheimer's
      disease, MixD) may also confer new insights pertaining to the possible
      interaction between neurodegenerative and vascular mechanisms in the pathogenesis
      of dementia. Liquid chromatography coupled to mass spectrometry was used to
      comprehensively analyze the lipidomes of white and gray matter from the temporal
      cortex of nondemented controls, SIVD, and MixD subjects. Detailed molecular
      profiles highlighted the pathologic relevance of gray matter sphingolipid fatty
      acyl chain heterogeneity in dementia. In addition, the levels of sulfatides and
      lysobisphosphatidic acids were progressively increased in the temporal cortex
      gray matter from control to SIVD to MixD. White matter phospholipid profiles
      indicated possible adaptive mechanisms (i.e., increased unsaturation) to chronic
      ischemia in SIVD and elevated membrane degradation in MixD. 

PMID- 24684788
TI  - Hippocampal subfield volumes at 7T in early Alzheimer's disease and normal aging.
AB  - We compared hippocampal subfield and entorhinal cortex (ERC) volumes between
      patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and
      controls without cognitive impairment. Additionally, we investigated the relation
      between age and hippocampal subfields and ERC in controls. We performed ultra
      high field 0.7 mm(3) 7Tesla magnetic resonance imaging in 16 patients with
      amnestic MCI, 9 with AD, and 29 controls. ERC, subiculum, cornu ammonis (CA)1,
      CA2, CA3, and dentate gyrus (DG)&CA4 were traced on T2-weighted images. Analyses
      of covariance, adjusted for age, sex, and intracranial volume showed that
      compared with controls and patients with MCI, patients with AD had significantly
      smaller ERC, subiculum, CA1, CA3, and DG&CA4 volumes. Trend analyses revealed
      similar associations between ERC and hippocampal subfields and diagnostic group.
      Older age was significantly associated with smaller CA1 and DG&CA4 volumes. In
      conclusion, almost all hippocampal subfields and ERC show volume reductions in
      patients with AD compared with controls and patients with MCI. Future, larger
      studies should determine which subfields are affected earliest in the disease
      process and what mechanisms underlie the volume loss.

PMID- 24684789
TI  - Reverse engineering of Alzheimer's disease based on biomarker pathways analysis.
AB  - Alzheimer's disease (AD) poses an increasingly profound problem to society, yet
      progress toward a genuine understanding of the disease remains worryingly slow.
      Perhaps, the most outstanding problem with the biology of AD is the question of
      its mechanistic origins, that is, it remains unclear wherein the molecular
      failures occur that underlie the disease. We demonstrate how molecular biomarkers
      could help define the nature of AD in terms of the early biochemical events that
      correlate with disease progression. We use a novel panel of biomolecules that
      appears in cerebrospinal fluid of AD patients. As changes in the relative
      abundance of these molecular markers are associated with progression to AD from
      mild cognitive impairment, we make the assumption that by tracking their origins
      we can identify the biochemical conditions that predispose their presence and
      consequently cause the onset of AD. We couple these protein markers with an
      analysis of a series of genetic factors and together this hypothesis essentially
      allows us to redefine AD in terms of the molecular pathways that underlie the
      disease.

PMID- 24684790
TI  - Neural correlates of age-related decline and compensation in visual attention
      capacity.
AB  - We identified neural correlates of declined and preserved basic visual attention
      functions in aging individuals based on Bundesen "Theory of Visual Attention". In
      an interindividual difference approach, we contrasted electrophysiology of higher
      and lower-performing younger and older participants. In both age groups, the
      same distinct components indexed performance levels of parameters visual
      processing speed C and visual short-term memory storage capacity K. The posterior
      N1 marked interindividual differences in C and the contralateral delay activity
      marked interindividual differences in K. Moreover, both parameters were
      selectively related to 2 further event-related potential waves in older age. The
      anterior N1 was reduced for older participants with lower processing speed,
      indicating that age-related loss of attentional resources slows encoding. An
      enhanced right-central positivity was found only for older participants with high
      storage capacity, suggesting compensatory recruitment for retaining visual short
      term memory performance. Together, our results demonstrate that attentional
      capacity in older age depends on both preservation and successful reorganization
      of the underlying brain circuits.

PMID- 24684791
TI  - Genetic variation of the retromer subunits VPS26A/B-VPS29 in Parkinson's disease.
AB  - We recently showed that mutation of the VPS35 gene can cause late-onset
      Parkinson's disease. In the present study we sequenced 702 affected subjects from
      the Mayo Clinic Parkinson's disease patient-control series for the VPS29 and
      VPS26A/B genes. We identified only 2 rare nonsynonymous variants in the VPS26A
      p.K93E and VPS29 p.N72H. The results show that mutations in the genes composing
      the retromer cargo recognition subunit are not a common cause of Parkinson's
      disease. 

PMID- 24684793
TI  - Serotonin transporter polymorphic region 5-HTTLPR modulates risk for Parkinson's
      disease.
AB  - The association between the serotonin transporter gene (SLC6A4) polymorphisms,
      that is, 5-HTTLPR and rs25531, and Parkinson's disease (PD) remains to be further
      defined. We investigated this relationship in a Chinese cohort that comprised 504
      PD patients and 504 controls. A total of 8 haplotypes and 14 genotypes of SLC6A4
      were found in this population including a new variant of 5-HTTLPR, that is, 20G.
      Our results presented that 5-HTTLPR was associated with an aggravated risk for PD
      (p = 0.005). The rs25531 alone is not associated with PD susceptibility. However,
      in a sub-classification based on the impact of 5-HTTLPR and rs25531 on 5-HTT
      expression, we observed a significant difference in 5-HTT expressing distribution
      in the cohort, accompanied by an apparently lower level of 5-HTT high expressing
      group, that is, the LALA genotype, in the PD patients. Taken together, our data
      provide novel insight in support that the SLC6A4 polymorphisms, particularly 5
      HTTLPR, and the serotonergic system are associated with PD etiology. 

PMID- 24684792
TI  - Respiratory chain deficiency in aged spinal motor neurons.
AB  - Sarcopenia, muscle wasting, and strength decline with age, is an important cause
      of loss of mobility in the elderly individuals. The underlying mechanisms are
      uncertain but likely to involve defects of motor nerve, neuromuscular junction,
      and muscle. Loss of motor neurons with age and subsequent denervation of skeletal
      muscle has been recognized as one of the contributing factors. This study
      investigated aspects of mitochondrial biology in spinal motor neurons from
      elderly subjects. We found that protein components of complex I of mitochondrial
      respiratory chain were reduced or absent in a proportion of aged motor neurons-a
      phenomenon not observed in fetal tissue. Further investigation showed that
      complex I-deficient cells had reduced mitochondrial DNA content and smaller soma
      size. We propose that mitochondrial dysfunction in these motor neurons could lead
      to the cell loss and ultimately denervation of muscle fibers. 

PMID- 24684794
TI  - Mutations in UBQLN2 and SIGMAR1 genes are rare in Korean patients with
      amyotrophic lateral sclerosis.
AB  - Mutations in the UBQLN2 and SIGMAR1 genes were recently identified in X-linked
      dominant amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS and/or
      FTD) and FTD and/or motor neuron disease, respectively. Subsequent studies,
      however, found that UBQLN2 mutations were rare, and the pathogenicity of SIGMAR1
      mutation in FTD and/or motor neuron disease was controversial. In the present
      study, we analyzed mutations in the UBQLN2 and SIGMAR1 genes in a Korean cohort
      of 258 patients with familial ALS (n = 9) or sporadic (sALS; n = 258) ALS. One
      novel UBQLN2 variant (p.D314E) was observed in 2 patients with sALS and 5 of 727
      controls indicating that this variant might be a rare polymorphism rather than a
      disease-causing mutation. A novel SIGMAR1 gene variant in the 3'-untranslated
      region (c.*58T>C) was found in 1 sALS and was absent in 727 control samples.
      Taken together, our data suggest that causative mutations in the UBQLN2 and
      SIGMAR1 genes are rare in Korean patients with either familial or sporadic ALS. 

PMID- 24684795
TI  - Aging-related neurodegeneration eliminates male courtship choice in Drosophila.
AB  - Choices between 2 options, one liked and one disliked, are effortless for an
      animal, whereas those among 2 equally liked options are more difficult to
      determine and might depend on an unknown mechanism. Here, we report that in the
      fruit fly Drosophila melanogaster, both younger virgin females and older ones are
      "liked options" to males. However, when given the choice, males tend to be
      fastidious and prefer younger virgin females to older ones. Besides, aging
      eliminates males' preference for younger mates, which can be mimicked by
      ectopically expressing the human amyloid precursor protein in their central
      nervous system. Furthermore, we examined the effect of neurodegeneration in
      Drosophila courtship circuit and confirmed that male courtship preference for
      younger mates was abrogated by neurodegeneration. Our work, thus characterizes a
      novel choice behavior that can be decisions after comparison and also reveals the
      critical role of neurodegeneration in this behavior, which provides new insights
      on decision-making mechanisms.

PMID- 24684797
TI  - Synthesis, characterization, and in vitro studies of PLGA-PEG nanoparticles for
      oral insulin delivery.
AB  - Therapeutic proteins and peptides are corresponding to a major area of research
      in biotechnology companies and current pharmaceutical. Because of their natural
      instability, the enormous majority of these drugs require parenteral
      administration. Oral insulin delivery would be a highly attractive alternative
      process of administration, though it continues to be a mysterious target due to
      the enzymatic digestion of insulin and low levels of absorption from the
      gastrointestinal region. Hydrogel polymers can be considered as potential
      carriers for oral insulin delivery. In particular, a pH responsive hydrogel
      composed of PLGA-PEG has shown the ability to protect insulin from enzymes in the
      gastric environment and release in small intestines. However, this material has
      not shown similar potential for oral protein delivery of further model drugs. To
      date, the unique interaction between PLGA-PEG and insulin, as a potential drug
      for oral delivery, is not completely understood. The focus of this research is
      synthetization and characterization of hydrogels PLGA-PEG insulin nanoparticles
      and also pH sensitivity of insulin nanoparticles was investigated. 

PMID- 24684796
TI  - Heritability and genetic association analysis of cognition in the Diabetes Heart
      Study.
AB  - Cognitive performance is an important component of healthy aging. Type 2 diabetes
      (T2D) is associated with negative outcomes for the brain and cognition, although
      causal mechanisms have not been definitely determined. Genetic risk factors
      warrant further consideration in this context. This study examined the
      heritability of cognitive function as assessed by (1) the Digit Symbol
      Substitution Task; (2) the Modified Mini-Mental State Examination; (3) the Stroop
      Task; (4) the Rey Auditory-Verbal Learning Task; and (5) the Controlled Oral Word
      Association Task for Phonemic and Semantic Fluency, in the family-based, T2D
      enriched, Diabetes Heart Study sample (n = 550 participants from 257 families).
      The genetic basis of these cognitive measures was further evaluated by
      association analysis with candidate single-nucleotide polymorphisms (SNPs) and
      genome-wide SNP data. Measures of cognitive function were significantly heritable
      (h^(2) = 0.28-0.62) following adjustment for age, gender, and education. A total
      of 31 SNPs (from 26 genes/regions) selected to form an a priori set of candidate
      SNPs showed limited evidence of association with cognitive function when applying
      conservative metrics of significance. Genome-wide assessment of both noncoding
      and coding variants revealed suggestive evidence of association for several
      coding variants including rs139509083 in CNST (p = 4.9 * 10(-9)), rs199968569 in
      PLAA (p = 4.9 * 10(-9)) and rs138487371 in PCDH8 (p = 3.7 * 10(-8)). The
      identification of a heritable component to cognitive performance in T2D suggests
      a role for genetic contributors to cognitive performance even in the presence of
      metabolic disease and other associated comorbidities and is supported by the
      identification of genetic association signals in functionally plausible
      candidates. 

PMID- 24684798
TI  - Food-related parenting: issues and challenges.

PMID- 24684800
TI  - Pattern of neurological disease seen among patients admitted in tertiary care
      hospital.
AB  - BACKGROUND: Neurologic disorders are not uncommon at in patient departments of
      different hospitals. We have conducted the study to see the pattern and burden of
      neurologic disorders at different inpatient departments of a tertiary care
      centre. METHODOLOGY: This retrospective observational study was carried out from
      the records and referral notes of neurology department of Dhaka Medical College
      Hospital (DMCH) from July 2011 to June 2012. A total 335 patients were evaluated
      by consultant neurologists during this period. RESULT: Majority of the patients
      (59.7%) presented after the age of forty years. The mean age at presentation was
      45.11 +/- 17.3 years with a male predominance (63.3%). Stroke was the most common
      condition (47.5%) observed at referral, followed by seizure (9.3%), disease of
      spinal cord (7.8%) and encephalopathy (6.3%). Even after consultation, 30
      patients remained undiagnosed and 6 were diagnosed as functional disorder.
      Department of Medicine (231, 69%) and Cardiology (61, 18.2%) made most of the
      calls. More than half (56%) of the stroke patients were referred from medicine
      and one third (35.2%) from cardiology. Seizure (67.7%), problem in spinal cord
      (92.3%), coma (50%), encephalopathy (57.1%), motor neuron disease (MND) (72.7%)
      were common reasons for referral from department of Medicine. Whereas patients
      with cord disease (7.3%), CNS tumor (40%), seizure disorder (6.5%) and stroke
      (3.8%) were referred from surgery. Department of Obstetrics and Gynecology sought
      help for stroke (2.5%), seizure (12.9%), MND (27.3%), coma (16.7%) and
      encephalopathy (9.5%). Hypertension, diabetes, ischemic heart disease,
      dyslipidaemia and respiratory problem were significantly associated co-morbid
      conditions in stroke patients (at 95% CI, p value is <0.001, <0.01, <0.001,
      <0.05, <0.05 respectively). Hematological disorders were common association among
      patients with cord problem (<0.05). CONCLUSION: Wide ranges of neurological
      problems are often managed by physicians and surgeons, especially those from
      medicine and cardiology. Where ever available consultation from neurologists can
      help in diagnosing and managing these cases.

PMID- 24684801
TI  - Overdose rescues by trained and untrained participants and change in opioid use
      among substance-using participants in overdose education and naloxone
      distribution programs: a retrospective cohort study.
AB  - BACKGROUND: One approach to preventing opioid overdose, a leading cause of
      premature, preventable mortality, is to provide overdose education and naloxone
      distribution (OEND). Two outstanding issues for OEND implementation include 1)
      the dissemination of OEND training from trained to untrained community members;
      and 2) the concern that OEND provides active substance users with a false sense
      of security resulting in increased opioid use. METHODS: To compare overdose
      rescue behaviors between trained and untrained rescuers among people reporting
      naloxone rescue kit use; and determine whether heroin use changed after OEND, we
      conducted a retrospective cohort study among substance users in the Massachusetts
      OEND program from 2006 to 2010. We used chi square and t-test statistics to
      compare the differences in overdose management characteristics among overdoses
      managed by trained versus untrained participants. We employed Wilcoxon signed
      rank test to compare median difference among two repeated measures of substance
      use among participants with drug use information collected more than once.
      RESULTS: Among 4,926 substance-using participants, 295 trained and 78 untrained
      participants reported one or more rescues, resulting in 599 rescue reports. We
      found no statistically significant differences in help-seeking (p = 0.41), rescue
      breathing (p = 0.54), staying with the victim (p = 0.84) or in the success of
      naloxone administration (p = 0.69) by trained versus untrained rescuers. We
      identified 325 OEND participants who had drug use information collected more than
      once. We found no significant overall change in the number of days using heroin
      in past 30 days (decreased 38%, increased 35%, did not change 27%, p = 0.52).
      CONCLUSION: Among 4926 substance users who participated in OEND, 373(7.6%)
      reported administering naloxone during an overdose rescue. We found few
      differences in behavior between trained and untrained overdose rescuers.
      Prospective studies will be needed to determine the optimal level of training and
      whether naloxone rescue kits can meet an over-the-counter standard. With no clear
      evidence of increased heroin use, this concern should not impede expansion of
      OEND programs or policies that support them.

PMID- 24684802
TI  - F-box protein complex FBXL19 regulates TGFbeta1-induced E-cadherin down
      regulation by mediating Rac3 ubiquitination and degradation.
AB  - BACKGROUND: Rac3 is a small GTPase multifunctional protein that regulates cell
      adhesion, migration, and differentiation. It has been considered as an oncogene
      in breast cancer; however, its role in esophageal cancer and the regulation of
      its stability have not been studied. F-box proteins are major subunits within the
      Skp1-Cullin-1-F-box (SCF) E3 ubiquitin ligases that recognize particular
      substrates for ubiquitination and proteasomal degradation. Recently, we have
      shown that SCFFBXL19 targets Rac1 and RhoA, thus regulating Rac1 and RhoA
      ubiquitination and degradation. Here, we demonstrate the role of FBXL19 in the
      regulation of Rac3 site-specific ubiquitination and stability. Expression of
      TGFbeta1 is associated with poor prognosis of esophageal cancer. TGFbeta1 reduces
      tumor suppressor, E-cadherin, expression in various epithelial-derived cancers.
      Here we investigate the role of FBXL19-mediated Rac3 degradation in TGFbeta1
      induced E-cadherin down-regulation in esophageal cancer cells. METHODS: FBXL19
      regulated endogenous and over-expressed Rac3 stability were determined by
      immunoblotting and co-immunoprecipitation. Esophageal cancer cells (OE19 and
      OE33) were used to investigate TGFbeta1-induced E-cadherin down-regulation by
      Immunoblotting and Immunostaining. RESULTS: Overexpression of FBXL19 decreased
      endogenous and over-expressed Rac3 expression by interacting and
      polyubiquitinating Rac3, while down-regulation of FBXL19 suppressed Rac3
      degradation. Lysine166 within Rac3 was identified as an ubiquitination acceptor
      site. The FBXL19 variant with truncation at the N-terminus resulted in an
      increase in Rac3 degradation; however, the FBXL19 variant with truncation at the
      C-terminus lost its ability to interact with Rac3 and ubiquitinate Rac3 protein.
      Further, we found that Rac3 plays a critical role in TGFbeta1-induced E-cadherin
      down-regulation in esophageal cancer cells. Over-expression of FBXL19 attenuated
      TGFbeta1-induced E-cadherin down-regulation and esophageal cancer cells
      elongation phenotype. CONCLUSIONS: Collectively these data unveil that FBXL19
      functions as an antagonist of Rac3 by regulating its stability and regulates the
      TGFbeta1-induced E-cadherin down-regulation. This study will provide a new
      potential therapeutic strategy to regulate TGFbeta1 signaling, thus suppressing
      esophageal tumorigenesis.

PMID- 24684803
TI  - Improvement of both fasting and postprandial glycemic control by the two-step
      addition of miglitol and mitiglinide to basal insulin therapy: a pilot study.
AB  - BACKGROUND: Combination therapy consisting of basal insulin and oral hypoglycemic
      agents (OHAs) is effective for the treatment of type 2 diabetes (T2DM) that
      cannot be adequately controlled using OHAs alone. Though basal insulin with
      metformin or sulfonylurea is an effective therapy, it cannot reduce postprandial
      glycemia without the risk of hypoglycemia. We examined a two-step regimen
      consisting of the addition of postprandial hypoglycemic agents (an alpha
      glucosidase inhibitor and a glinide) in patients whose T2DM was poorly controlled
      using basal insulin therapy. METHODS: Inpatients between the ages of 30-79 years
      who had T2DM and an HbA1c level of more than 7.0% were recruited. The patients
      were treated with once-daily insulin glargine with or without metformin,
      depending on the patient's age and renal function. Insulin glargine was titrated
      to achieve a target fasting glucose level of 70-130 mg/dL as a first step
      (STEP0). If the 2-hour postprandial glucose (PBG) level was higher than the
      target of 180 mg/dL, miglitol treatment (150 mg/day) was initiated, with dose
      adjustments (75-225 mg) allowed depending on abdominal symptoms and the PBG
      (STEP1). If the PBG of the patients remained higher than the target after 3 days
      of treatment, mitiglinide (30 mg/day, titrated up to 60 mg) was added (STEP2). We
      then evaluated the proportion of patients who achieved the target PBG before and
      after the two-step regimen. Continuous Glucose Monitoring (CGM) was performed
      throughout the two-step protocol in most of the patients. RESULTS: Of the 16
      patients who were recruited (median age, 67.0 [58.0-71.0] years; body mass index,
      25.0 [22.0-27.9] kg/m(2); HbA1c level at admission, 9.1% [8.35-10.4%]), 1 patient
      (6.25%) achieved the target PBG at STEP 0 and 14 patients (87.5%) had achieved
      the target PBG at the end of the treatment protocol (P = 0.002). CGM showed a
      significant decrease in the glucose level at each step of the protocol. The
      standard deviations in the CGM glucose levels for 24 hours, MAGE, and M-value
      also improved. CONCLUSIONS: The two-step addition of postprandial hypoglycemic
      agents to basal insulin therapy is potentially effective and safe for decreasing
      both the fasting and postprandial glucose levels.

PMID- 24684804
TI  - Angiographic outcome of endovascular stroke therapy correlated with MR findings,
      infarct growth, and clinical outcome in the DEFUSE 2 trial.
AB  - BACKGROUND: DEFUSE 2 demonstrated that patients with magnetic resonance imaging
      mismatch had a favorable clinical response to tissue reperfusion assessed by
      magnetic resonance imaging. This study reports the endovascular results and
      correlates angiographic reperfusion with clinical and imaging outcomes. METHODS:
      Prospectively enrolled ischemic stroke patients underwent baseline magnetic
      resonance imaging and started endovascular therapy within 12 h of onset. Patients
      were classified as either target mismatch or no target mismatch using magnetic
      resonance imaging. The pre- and postprocedure angiogram was evaluated to
      determine thrombolysis in cerebral infarction scores. Favorable clinical response
      was determined at day 30, and good functional outcome was defined as a modified
      Rankin Scale 0-2 at day 90. RESULTS: One-hundred patients had attempted
      endovascular treatment. At procedure end, 23% were thrombolysis in cerebral
      infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in
      cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More
      favorable thrombolysis in cerebral infarction-reperfusion scores were associated
      with greater magnetic resonance imaging reperfusion (P<0.001). thrombolysis in
      cerebral infarction scores correlated with 30-day favorable clinical response
      (P=0.041) and 90-day modified Rankin Scale 0-2 (P=0.008). These correlations were
      significant for target mismatch patients at 30 days (P=0.034) and 90 days
      (P=0.003). Infarct growth was strongly associated with poorer thrombolysis in
      cerebral infarction scores in target mismatch patients (P<0.001). Patients with
      thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic
      resonance imaging reperfusion (P=0.004) and poorer clinical outcome at 90 days
      (P=0.01) compared with thrombolysis in cerebral infarction 2B-3 patients.
      CONCLUSION: Thrombolysis in cerebral infarction reperfusion following
      endovascular therapy for ischemic stroke is highly correlated with magnetic
      resonance imaging reperfusion, infarct growth, and clinical outcome.

PMID- 24684806
TI  - Novel missense mutation in the FH gene in familial renal cell cancer patients
      lacking cutaneous leiomyomas.
AB  - BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare
      tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas
      and papillary type 2 renal cell cancer. Germline mutation of the fumarate
      hydratase (FH) gene is known to be associated with HLRCC. CASE PRESENTATION: We
      describe a 64-year-old father and his 39-year-old son with HLRCC who developed
      papillary type 2 RCCs lacking cutaneous leiomyomas at any site. A common missense
      mutation in the FH gene, (c.1021G > A, p.D341N) in exon 7, was detected in the 2
      cases. Functional prediction with the bioinformatics programs, SIFT and Polyphen
      2, reported "damaging (SIFT score 0.00)" and "probably damaging (PSIC score
      1.621)" values, respectively. In 162 healthy individuals, there were no cases of
      a G transition to any base. Finally, (c.1021G > A) in exon 7, was identified as a
      point mutation. CONCLUSION: We report a family with HLRCC in which a novel
      missense mutation was detected. A familial papillary type 2 renal cancer should
      be considered HLRCC unless typical cutaneous leiomyomas do not occur.

PMID- 24684805
TI  - Identification of candidate genes for drought tolerance by whole-genome
      resequencing in maize.
AB  - BACKGROUND: Drought stress is one of the major limiting factors for maize
      production. With the availability of maize B73 reference genome and whole-genome
      resequencing of 15 maize inbreds, common variants (CV) and clustering analyses
      were applied to identify non-synonymous SNPs (nsSNPs) and corresponding candidate
      genes for drought tolerance. RESULTS: A total of 524 nsSNPs that were associated
      with 271 candidate genes involved in plant hormone regulation, carbohydrate and
      sugar metabolism, signaling molecules regulation, redox reaction and acclimation
      of photosynthesis to environment were detected by CV and cluster analyses. Most
      of the nsSNPs identified were clustered in bin 1.07 region that harbored six
      previously reported QTL with relatively high phenotypic variation explained for
      drought tolerance. Genes Ontology (GO) analysis of candidate genes revealed that
      there were 35 GO terms related to biotic stimulus and membrane-bounded organelle,
      showing significant differences between the candidate genes and the reference B73
      background. Changes of expression level in these candidate genes for drought
      tolerance were detected using RNA sequencing for fertilized ovary, basal leaf
      meristem tissue and roots collected under drought stressed and well-watered
      conditions. The results indicated that 70% of candidate genes showed
      significantly expression changes under two water treatments and our strategies
      for mining candidate genes are feasible and relatively efficient. CONCLUSIONS:
      Our results successfully revealed candidate nsSNPs and associated genes for
      drought tolerance by comparative sequence analysis of 16 maize inbred lines. Both
      methods we applied were proved to be efficient for identifying candidate genes
      for complex traits through the next-generation sequencing technologies (NGS).
      These selected genes will not only facilitate understanding of genetic basis of
      drought stress response, but also accelerate genetic improvement through marker
      assisted selection in maize.

PMID- 24684807
TI  - Introducing intravascular microdialysis for continuous lactate monitoring in
      patients undergoing cardiac surgery: a prospective observational study.
AB  - INTRODUCTION: Lactate is a marker of hypoperfusion and may be used for risk
      assessment in critically ill patients. Although evidence suggests that repeated
      lactate measurements are of clinical interest, how and when lactate should be
      analyzed is controversial. Intravascular microdialysis provides a novel method
      for the continuous monitoring of lactate, which may be clinically beneficial in
      critically ill patients. METHODS: Circulating lactate levels were continuously
      monitored in 80 patients undergoing cardiac surgery using either a separate
      single-lumen microdialysis catheter or a triple-lumen central venous catheter
      with an integrated microdialysis function. The catheter was placed with the tip
      positioned in the superior vena cava. Arterial blood gas samples were taken every
      hour to obtain reference values, and the lactate levels were analyzed in a blood
      gas analyzer. RESULTS: A total of 1,601 paired microdialysis-arterial blood gas
      lactate samples were obtained. Bland-Altman analysis showed a bias (mean
      difference) +/- limits of agreement (+/-1.96 SD) of 0.02 +/- 0.42 mmol/L. The
      regression coefficient was 0.98 (P = 0.0001). CONCLUSIONS: Central venous
      microdialysis is an accurate and reliable method for continuous blood lactate
      monitoring in patients undergoing cardiac surgery. The system may be useful for
      early lactate-guided therapy in critically ill patients.

PMID- 24684808
TI  - Effects of task-oriented robot training on arm function, activity, and quality of
      life in chronic stroke patients: a randomized controlled trial.
AB  - BACKGROUND: Over fifty percent of stroke patients experience chronic arm hand
      performance problems, compromising independence in daily life activities and
      quality of life. Task-oriented training may improve arm hand performance after
      stroke, whereby augmented therapy may lead to a better treatment outcome.
      Technology-supported training holds opportunities for increasing training
      intensity. However, the effects of robot-supported task-oriented training with
      real life objects in stroke patients are not known to date. The aim of the
      present study was to investigate the effectiveness and added value of the Haptic
      Master robot combined with task-oriented arm hand training in chronic stroke
      patients. METHODS: In a single-blind randomized controlled trial, 22 chronic
      stroke patients were randomly allocated to receive either task-oriented robot
      assisted arm-hand training (experimental group) or task-oriented non-robotic arm
      hand training (control group). For training, the T-TOAT (Technology-supported
      Task-Oriented Arm Training) method was applied. Training was provided during 8
      weeks, 4 times/week, 2 * 30 min/day. RESULTS: A significant improvement after
      training on the Action Research Arm Test (ARAT) was demonstrated in the
      experimental group (p = 0.008). Results were maintained until 6 months after
      cessation of the training. On the perceived performance measure (Motor Activity
      Log (MAL)), both, the experimental and control group improved significantly after
      training (control group p = 0.008; experimental group p = 0.013). The
      improvements on MAL in both groups were maintained until 6 months after cessation
      of the training. With regard to quality of life, only in the control group a
      significant improvement after training was found (EuroQol-5D p = 0.015, SF-36
      physical p = 0.01). However, the improvement on SF-36 in the control group was
      not maintained (p = 0.012). No between-group differences could be demonstrated on
      any of the outcome measures. CONCLUSION: Arm hand performance improved in chronic
      stroke patients, after eight weeks of task oriented training. The use of a Haptic
      Master robot in support of task-oriented arm training did not show additional
      value over the video-instructed task-oriented exercises in highly functional
      stroke patients. CLINICAL TRIAL REGISTRATION INFORMATION: Current Controlled
      Trials ISRCTN82787126.

PMID- 24684809
TI  - The health-related quality of life among pre-diabetics and its association with
      body mass index and physical activity in a semi-urban community in Malaysia--a
      cross sectional study.
AB  - BACKGROUND: People with pre-diabetes are at high risk of developing type 2
      diabetes and cardiovascular diseases. Measurements of health-related quality of
      life (HRQOL) among pre-diabetics enable the health care providers to understand
      their overall health status and planning of interventions to prevent type 2
      diabetes. Therefore we aimed to determine the HRQOL and physical activity level;
      and its association with Body Mass Index (BMI) among pre-diabetics. METHODS: This
      was a cross sectional study carried out in two primary care clinics in a semi
      urban locality of Ampangan, Negeri Sembilan, Malaysia. Data was collected through
      self-administered questionnaires assessing the demographic characteristics,
      medical history, lifestyle and physical activity. The Short Form 36-items health
      survey was used to measure HRQOL among the pre-diabetics. Data entry and analysis
      were performed using the SPSS version 19. RESULTS: A total of 268 eligible pre
      diabetics participated in this study. The prevalence of normal weight, overweight
      and obesity were 7.1%, 21.6% and 71.3% respectively. Their mean (SD) age was 52.5
      (8.3) years and 64.2% were females. Among the obese pre-diabetics, 42.2% had both
      IFG and IGT, 47.0% had isolated IFG and 10.8% had isolated IGT, 36.2% had
      combination of hypertension, dyslipidemia and musculoskeletal diseases. More than
      53.4% of the obese pre-diabetics had family history of diabetes, 15.7% were
      smokers and 60.8% were physically inactive with mean PA of <600 MET-minutes/week.
      After adjusted for co-variants, Physical Component Summary (PCS) was
      significantly associated with BMI categories [F (2,262)=11.73, p<0.001] where pre
      diabetics with normal weight and overweight had significantly higher PCS than
      those obese; normal vs obese [Mdiff=9.84, p=0.006, 95% CIdiff=2.28, 17.40] and
      between overweight vs obese [Mdiff=8.14, p<0.001, 95% CIdiff=3.46, 12.80].
      CONCLUSION: Pre-diabetics who were of normal weight reported higher HRQOL
      compared to those overweight and obese. These results suggest a potentially
      greater risk of poor HRQOL among pre-diabetics who were overweight and obese
      especially with regard to the physical health component. Promoting recommended
      amount of physical activity and weight control are particularly important
      interventions for pre-diabetics at the primary care level.

PMID- 24684810
TI  - A risk score model predictive of the presence of additional disease in the axilla
      in early-breast cancer patients with one or two metastatic sentinel lymph nodes.
AB  - BACKGROUND: Axillary lymph node dissection (ALND) in early-breast cancer patients
      with positive sentinel node (SLN+) may not always be necessary. AIMS: To predict
      the finding of >=1 metastatic axillary node in addition to SLN+(s); to
      discriminate between patients who would or not benefit from ALND. METHODS:
      Records of 397 consecutive patients with 1-2 SLN+s receiving ALND were reviewed.
      Clinico-pathological features were used in univariate and multivariate analyses
      to develop a logistic regression model predictive of the risk of >=1 additional
      axillary node involved. The discrimination power of the model was quantified by
      the area under the receiver operating characteristic curve (AUC) and validated
      using an independent set of 83 patients. RESULTS: In univariate analyses, the
      risk of >=1 additional node involved was correlated with tumor size, grade, HER-2
      and Ki-67 over-expression, number of SLN+s. All factors, but Ki-67, retained in
      multivariate regressions were used to generate a predictive model with good
      discriminating power on both the training and the validation sets (AUC 0.73 and
      0.75, respectively). Three patient groups were defined based on their risk to
      present additional axillary burden. CONCLUSIONS: The model identifies SLN+
      patients at low risk (<=15%) who could reasonably be spared ALND and those at
      high risk (>75%) who should receive ALND. For patients at intermediate risk, ALND
      appropriateness could be individually evaluated based on other clinico
      pathological parameters.

PMID- 24684814
TI  - Long-term seizure outcome in patients with juvenile absence epilepsy; a
      retrospective study in a tertiary referral center.
AB  - PURPOSE: The study aim was to evaluate pharmacotherapy effects and long-term
      seizure outcomes in patients with juvenile absence epilepsy (JAE) during a five
      year follow-up period. The secondary aim was to identify factors from patient
      history and determine their influence on seizure control. METHOD: We
      retrospectively studied 46 patients with JAE in the period between 2006 and 2011.
      The age at seizure onset, onset seizure type, family history of epilepsy, status
      epilepticus in history, medication history, and the rate of seizure control were
      studied. RESULTS: There were 30 females (65.2%) and 16 males (34.8%) in the
      study. The mean age at seizure onset was 12.9+/-5.6 years (ranged from 3 to 28
      years). In 30 patients (65.2%), seizure onset was with absences, in 15 patients
      (32.6%) with generalized tonic-clonic seizure (GTCS), and in 1 patient (2.2%)
      with absence status. In 43 patients (93.5%), GTCS occurred in the course of the
      disease. Family history for epilepsy was positive in 10 patients (21.7%). In the
      five-year follow-up period, seizure freedom (Group 1) was achieved in 7 patients
      (15.2%). In total, 22 patients (47.8%) were classified into the groups involving
      very poor seizure control and antiepileptic drug resistance (Groups 5 and 6). The
      mean number of antiepileptic drugs (AEDs) used in the course of the disease in
      appropriate therapeutic doses was 3.8+/-2.3 (1-10 AEDs). CONCLUSION: The study
      results show that almost half of JAE patients have poor seizure control with a
      high rate of pharmacoresistance. The outcome of JAE can be very uncertain.

PMID- 24684813
TI  - Ankle voluntary movement enhancement following robotic-assisted locomotor
      training in spinal cord injury.
AB  - BACKGROUND: In incomplete spinal cord injury (iSCI), sensorimotor impairments
      result in severe limitations to ambulation. To improve walking capacity, physical
      therapies using robotic-assisted locomotor devices, such as the Lokomat, have
      been developed. Following locomotor training, an improvement in gait capabilities
      characterized by increases in the over-ground walking speed and endurance-is
      generally observed in patients. To better understand the mechanisms underlying
      these improvements, we studied the effects of Lokomat training on impaired ankle
      voluntary movement, known to be an important limiting factor in gait for iSCI
      patients. METHODS: Fifteen chronic iSCI subjects performed twelve 1-hour sessions
      of Lokomat training over the course of a month. The voluntary movement was
      qualified by measuring active range of motion, maximal velocity peak and
      trajectory smoothness for the spastic ankle during a movement from full plantar
      flexion (PF) to full dorsi-flexion (DF) at the patient's maximum speed. Dorsi-
      and plantar-flexor muscle strength was quantified by isometric maximal voluntary
      contraction (MVC). Clinical assessments were also performed using the Timed Up
      and Go (TUG), the 10-meter walk (10MWT) and the 6-minute walk (6MWT) tests. All
      evaluations were performed both before and after the training and were compared
      to a control group of fifteen iSCI patients. RESULTS: After the Lokomat training,
      the active range of motion, the maximal velocity, and the movement smoothness
      were significantly improved in the voluntary movement. Patients also exhibited an
      improvement in the MVC for their ankle dorsi- and plantar-flexor muscles. In
      terms of functional activity, we observed an enhancement in the mobility (TUG)
      and the over-ground gait velocity (10MWT) with training. Correlation tests
      indicated a significant relationship between ankle voluntary movement performance
      and the walking clinical assessments. CONCLUSIONS: The improvements of the
      kinematic and kinetic parameters of the ankle voluntary movement, and their
      correlation with the functional assessments, support the therapeutic effect of
      robotic-assisted locomotor training on motor impairment in chronic iSCI.

PMID- 24684815
TI  - Shifts in microbial community in response to dissolved oxygen levels in activated
      sludge.
AB  - This study evaluates the degradative efficiency of activated biomass collected
      from a Common Effluent Treatment Plant (CETP) under three different dissolved
      oxygen (DO) levels, 1, 2 and 4mgl(-1). The change in bacterial diversity with
      reference to DO levels was also analyzed. Results demonstrate that degradative
      efficiency was the highest, when the reactor was maintained at 4mgl(-1) DO, but
      amplicon library analysis showed a greater diversity of bacteria in the reactor
      maintained at 2mgl(-1) DO. Bacteria belonging to the order Desulfuromonadales,
      Entomoplasmatales, Pasteurellales, Thermales and Chloroflexales have only been
      detected in this reactor. Ammonia and nitrate levels in all three reactors
      indicated efficient nitrification process. Results of this study offer new
      insights into understanding the performance of activated biomass vis-a-vis
      microbial diversity and degradative efficiency with reference to DO. This
      information would be useful in improving the efficiency of any wastewater
      treatment plant. 

PMID- 24684816
TI  - Evaluation of electricity generation from ultrasonic and heat/alkaline
      pretreatment of different sludge types using microbial fuel cells.
AB  - This study investigated the effects of different sludge pretreatment methods
      (ultrasonic vs. combined heat/alkali) with varied sources of municipal sewage
      sludge (primary sludge (PS), secondary excess sludge (ES), anaerobic digestion
      sludge (ADS)) on electricity generation in microbial fuel cells (MFCs).
      Introduction of ultrasonically pretreated sludge (PS, ES, ADS) to MFCs generated
      maximum power densities of 13.59, 9.78 and 12.67mW/m(2) and soluble COD (SCOD)
      removal efficiencies of 87%, 90% and 57%, respectively. The sludge pretreated by
      combined heat/alkali (0.04N NaOH at 120 degrees C for 1h) produced maximum power
      densities of 10.03, 5.21 and 12.53mW/m(2) and SCOD removal efficiencies of 83%,
      75% and 74% with PS, ES and ADS samples, respectively. Higher SCOD by sludge
      pretreatment enhanced performance of the MFCs and the electricity generation was
      linearly proportional to the SCOD removal, especially for ES. 

PMID- 24684817
TI  - Waste degradation and gas production with enzymatic enhancement in anaerobic and
      aerobic landfill bioreactors.
AB  - The presence of lignin is the limiting factor at later stages of biodegradation
      of municipal solid waste under aerobic or anaerobic conditions. Supplying enzymes
      into the system could facilitate lignin degradation, thereby aiding anaerobic and
      aerobic waste degradation processes. A comprehensive set of laboratory
      experiments were conducted under both anaerobic and aerobic conditions to
      evaluate the feasibility of using enzymes in accelerating lignin-rich waste
      degradation. After 30 days of anaerobic operation, MnP and LiP enzyme treated
      reactors produced 36 and 23 times higher cumulative methane (CH4), respectively,
      compared to that of the control reactor devoid of enzyme treatments. The carbon
      dioxide (CO2) yield of MnP enhanced aerobic reactor showed more than two-fold
      increase.

PMID- 24684818
TI  - [GRADE: Methodology for formulating and grading recommendations in clinical
      practice].
AB  - Clinical practice guidelines (CPG) provide recommendations on the benefits and
      harms of different healthcare interventions. Proper CPG development and
      implementation can potentially reduce variability in clinical practice while
      improving its quality and safety. The GRADE system is used to assess the quality
      of evidence and to grade the strength of recommendations in the context of the
      development of CPGs, systematic reviews or health technology assessments. The aim
      of this article is to describe the main characteristics of the GRADE system
      through relevant examples in the context of primary care. 

PMID- 24684819
TI  - Psychosocial care to affected citizens and communities in case of CBRN incidents:
      a systematic review.
AB  - Disasters are associated with a substantial psychosocial burden for affected
      individuals (including first responders) and communities. Knowledge about how to
      address these risks and problems is valuable for societies worldwide. Decades of
      research into post-disaster psychosocial care has resulted in various
      recommendations and general guidelines. However, as CBRN (chemical, biological,
      radiological, nuclear) events form a distinctive theme in emergency planning and
      disaster preparedness, it is important to systematically explore their
      implications for psychosocial care. The aim of this study is to answer two
      questions: 1). To what extent does psychosocial care in the case of CBRN events
      differ from other types of events? 2). How strong is the scientific evidence for
      the effectiveness of psychosocial care interventions in the context of a CBRN
      event? A systematic literature review was conducted. Searches were performed in
      Medline, PsychINFO, Embase and PILOTS. Studies since January 2000 were included
      and evaluated by independent reviewers. The 39 included studies contain
      recommendations, primarily based on unsystematic literature reviews, qualitative
      research and expert opinions. Recommendations address: 1) public risk- and crisis
      communication, 2) training, education and exercise of responders, 3) support, and
      4) psychosocial counselling and care to citizens and responders. Although none of
      the studies meet the design criteria for effectiveness research, a substantial
      amount of consensus exists on aspects relevant to CBRN related psychosocial care.
      Recommendations are similar or complementary to general post-disaster
      psychosocial care guidelines. Notable differences are the emphasis on risk
      communication and specific preparation needs. Relevant recurring topics are
      uncertainty about contamination and health effects, how people will overwhelm
      health care systems, and the possibility that professionals are less likely to
      respond. However, the lack of evidence on effectiveness makes it necessary to be
      careful with recommendations. More evaluation research is absolutely needed. 

PMID- 24684820
TI  - Managing mass casualties and decontamination.
AB  - Careful planning and regular exercising of capabilities is the key to
      implementing an effective response following the release of hazardous materials,
      although ad hoc changes may be inevitable. Critical actions which require
      immediate implementation at an incident are evacuation, followed by disrobing
      (removal of clothes) and decontamination. The latter can be achieved through
      bespoke response facilities or various interim methods which may utilise water or
      readily available (dry, absorbent) materials. Following transfer to a safe
      holding area, each casualty's personal details should be recorded to facilitate a
      health surveillance programme, should it become apparent that the original
      contaminant has chronic health effects. 

PMID- 24684821
TI  - Chemerin levels as predictor of acute coronary events: a case-control study
      nested within the veterans affairs normative aging study.
AB  - OBJECTIVE: Chemerin is a recently identified adipocytokine that has been
      positively correlated with the presence and severity of coronary artery disease
      (CAD). However, no studies have examined circulating chemerin levels as a
      predictor of acute coronary syndrome (ACS). The purpose of this study is to
      evaluate whether chemerin levels predict the onset of ACS. MATERIALS/METHODS: We
      studied 90 men whose serum had been collected at least 2 years before the
      development of ACS, and 162 controls matched with the cases in a 1:2 fashion for
      age and year of collection. The mean age of the cohort was 66.3+/-9.6 years
      (range 34-84 years). Serum chemerin levels were measured with a commercially
      available enzyme-linked immunosorbent assay. RESULTS: Age was positively
      associated with chemerin levels (r=0.39, p<0.001). Logistic regression analysis,
      adjusting for years since blood collection, demonstrated a null association
      between chemerin levels and the odds ratio for development of ACS (OR: 0.99, 95%
      CI [0.99-1.001]). This association remained null after adjusting for age (OR:
      0.99 95% CI [0.99-1.001]). CONCLUSIONS: Although cross-sectional and case-control
      studies suggest a positive association between chemerin levels and CAD, we
      demonstrate that chemerin levels do not predict the development of ACS.

PMID- 24684822
TI  - Effects of individual branched-chain amino acids deprivation on insulin
      sensitivity and glucose metabolism in mice.
AB  - OBJECTIVE: We recently discovered that leucine deprivation increases hepatic
      insulin sensitivity via general control nondepressible (GCN) 2/mammalian target
      of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways. The goal of
      the present study was to investigate whether the above effects were leucine
      specific or were also induced by deficiency of other branched chain amino acids
      including valine and isoleucine. METHODS: Following depletion of BCAAs, changes
      in metabolic parameters and the expression of genes and proteins involved in
      regulation of insulin sensitivity and glucose metabolism were analyzed in mice
      and cell lines including human HepG2 cells, primary mouse hepatocytes and a mouse
      myoblast cell line C2C12. RESULTS: Valine or isoleucine deprivation for 7 days
      has similar effect on improving insulin sensitivity as leucine, in wild type and
      insulin-resistant mice models. These effects are possibly mediated by decreased
      mTOR/S6K1 and increased AMPK signaling pathways, in a GCN2-dependent manner.
      Similar observations were obtained in in vitro studies. In contrast to leucine
      withdrawal, valine or isoleucine deprivation for 7 days significantly decreased
      fed blood glucose levels, possibly due to reduced expression of a key
      gluconeogenesis gene, glucose-6-phosphatase. Finally, insulin sensitivity was
      rapidly improved in mice 1 day following maintenance on a diet deficient for any
      individual BCAAs. CONCLUSIONS: Our results show that while improvement on insulin
      sensitivity is a general feature of BCAAs depletion, individual BCAAs have
      specific effects on metabolic pathways, including those that regulate glucose
      level. These observations provide a conceptual framework for delineating the
      molecular mechanisms that underlie amino acid regulation of insulin sensitivity.

PMID- 24684823
TI  - Superantigen activates the gp130 receptor on adipocytes resulting in altered
      adipocyte metabolism.
AB  - OBJECTIVE: The bacteria Staphylococcus aureus is part of the normal bacterial
      flora and produces a repertoire of enterotoxins which can cause food poisoning
      and toxic shock and might contribute to the pathogenesis of inflammatory
      diseases. These enterotoxins directly cross-link the T cell receptor with MHC
      class II, activating large amounts of T cells and are therefore called
      superantigens. It was recently discovered that the superantigen SEA binds to the
      cytokine receptor gp130. As obesity and type 2 diabetes are highly associated
      with inflammation of the adipose tissue and gp130 has been shown to play an
      important role in adipocytes, we wanted to investigate the effect of SEA on
      adipocyte signaling and function. MATERIALS/METHODS: Binding of SEA to gp130 was
      examined using surface plasmon resonance in a cell free system. Effects of SEA on
      adipocyte signaling, insulin sensitivity and function were studied using western
      blotting and biological assays for lipolysis, lipogenesis and glucose uptake.
      RESULTS: We demonstrate that SEA binds to gp130 with a medium affinity.
      Furthermore, SEA induces phosphorylation of a key downstream target, STAT3, in
      adipocytes. SEA also inhibits insulin-induced activation of PKB and PKB
      downstream signaling which was associated with reduced basal and insulin induced
      glucose uptake, reduced lipogenesis as well as reduced ability of insulin to
      inhibit lipolysis. CONCLUSIONS: SEA inhibits insulin signaling as well as insulin
      biological responses in adipocytes supporting that bacterial infection might
      contribute to the development of insulin resistance and type 2 diabetes.

PMID- 24684824
TI  - Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced
      obese mice and obese-diabetic ob/ob mice.
AB  - OBJECTIVE: We investigated whether KR-66195, a new synthetic dipeptidyl
      dipeptidase IV inhibitor, could prevent weight gain, as well as improving
      glycemic control in diet-induced obese (DIO) and ob/ob mice. MATERIALS/METHODS:
      Male C57BL/6 mice were randomly assigned to the following groups: chow diet, high
      fat diet, and high-fat diet with KR-66195. After KR-66195 treatment for eight
      weeks, intraperitoneal glucose tolerance tests were performed. A pair-feeding
      study was performed to investigate the mechanisms of the anti-obesity effects of
      KR-66195 in DIO mice. Female ob/ob mice were treated with KR-66195 for three
      weeks and compared to the vehicle-treated group. RESULTS: In DIO mice, KR-66195
      treatment increased the plasma glucagon-like peptide (GLP)-1 levels and improved
      glucose tolerance. This treatment also reduced body weight gain (5.38+/-0.94 g
      vs. 12.08+/-0.55 g, P<0.01) and food intake (2.41+/-0.09 g vs. 2.79+/-0.11 g,
      P<0.05). In ob/ob mice, KR-66195 treatment for three weeks resulted in comparable
      effects in DIO mice. In the pair-feeding study, KR-66195-treated mice exhibited a
      16% increase in energy expenditure (kcal/h/kg lean body mass) without significant
      differences in body weight or activities compared with pair-fed mice. These
      results suggest that KR-66195 prevented weight gain in DIO mice by decreasing
      food intake, as well as increasing energy expenditure. CONCLUSIONS: KR-66195
      markedly increased plasma levels of GLP-1, resulting in the probable improvement
      in glucose tolerance and reduced body weight and food intake. Thus, KR-66195
      might be further developed as a therapeutic drug to treat obesity, as well as
      diabetes.

PMID- 24684825
TI  - Markers of endothelial cell dysfunction are increased in human omental adipose
      tissue from women with pre-existing maternal obesity and gestational diabetes.
AB  - OBJECTIVE: To determine the effect of maternal obesity and gestational diabetes
      mellitus (GDM) on the expression and release of genes involved in endothelial
      cell dysfunction in human placenta and omental adipose tissue. MATERIALS/METHODS:
      Human placenta and omental adipose tissue were obtained from non-obese and obese
      normal glucose tolerant (NGT) women and women with GDM at the time of Caesarean
      section. Quantitative RT-PCR was performed to determine the level of expression.
      Tissue explants were performed to determine the release of proteins of interest.
      RESULTS: There was no effect of pre-existing maternal obesity or GDM on placental
      gene expression or secretion of members of the VEGF family members (PLGF and VEGF
      A expression and secretion; sFlt-1 release; VEGFR1 and VEGFR2 mRNA expression);
      FGFR1 mRNA expression, FGF2 mRNA expression and secretion; endoglin mRNA
      expression and secretion (sEng); and the adhesion molecules ICAM-1 and VCAM-1. On
      the other hand, in omental adipose tissue, pre-existing maternal obesity and GDM
      were associated with increased gene expression of PLGF, endoglin and ICAM-1 and
      increased secretion of PLGF, sFlt-1, FGF2, sEng and sICAM-1. There was, however,
      no effect of maternal pre-existing obesity and GDM on VEGF-A, VEGFR1, VEGFR2,
      FGFR1 and VCAM-1 expression or secretion. CONCLUSIONS: This study demonstrated
      the presence of abnormal expression and secretion of angiogenic proteins and
      adhesion molecules in omental adipose tissue, but not placenta, from pregnant
      women with GDM and pre-existing maternal obesity. Increased angiogenic and
      adhesion molecules released from adipose tissue may affect angiogenesis,
      inflammation and or lipid and glucose metabolism in both mum and her offspring.

PMID- 24684826
TI  - Three-dimensional reconstruction of the human skeletal muscle mitochondrial
      network as a tool to assess mitochondrial content and structural organization.
AB  - AIM: Mitochondria undergo continuous changes in shape as result of complex fusion
      and fission processes. The physiological relevance of mitochondrial dynamics is
      still unclear. In the field of mitochondria bioenergetics, there is a need of
      tools to assess cell mitochondrial content. To develop a method to visualize
      mitochondrial networks in high resolution and assess mitochondrial volume.
      METHODS: Confocal fluorescence microscopy imaging of mitochondrial network stains
      in human vastus lateralis single muscle fibres and focused ion beam/ scanning
      electron microscopy (FIB/SEM) imaging, combined with 3D reconstruction was used
      as a tool to analyse mitochondrial morphology and measure mitochondrial
      fractional volume. RESULTS: Most type I and type II muscle fibres have tubular
      highly interconnected profusion mitochondria, which are thicker and more
      structured in type I muscle fibres (Fig. 1). In some muscle fibres, profission
      isolated ellipsoid-shaped mitochondria were observed. Mitochondrial volume was
      significantly higher in type I muscle fibres and showed no correlation with any
      of the investigated molecular and biochemical mitochondrial measurements (Fig.
      2). Three-dimensional reconstruction of FIB/SEM data sets shows that some
      subsarcolemmal mitochondria are physically interconnected with some
      intermyofibrillar mitochondria (Fig. 3). CONCLUSION: Two microscopy methods to
      visualize skeletal muscle mitochondrial networks in 3D are described and can be
      used as tools to investigate mitochondrial dynamics in response to life-style
      interventions and/or in certain pathologies. Our results question the
      classification of mitochondria into subsarcolemmal and intermyofibrillar pools,
      as they are physically interconnected.

PMID- 24684827
TI  - Autochthonous canine leishmaniasis in Romania: neglected or (re)emerging?
AB  - Canine leishmaniasis is a vector-borne zoonotic disease caused by the protozoan
      parasite Leishmania infantum. In Romania between 1955 and 2013, no cases of human
      autochthonous visceral leishmaniasis were reported. Data regarding canine
      leishmaniasis is similarly scarce. Since the first report of clinical
      autochthonous canine leishmaniasis in 1935, there were only three sporadic
      reports of positive dogs all without any clinical signs. Our study reports the
      first clinical case of autochthonous canine leishmaniasis in the last 80 years,
      stressing the importance of a targeted surveillance of Leishmania infection, as
      infected dogs act as the primary reservoir for zoonotic visceral leishmaniasis. 

PMID- 24684828
TI  - Mechanical testing of a device for subcutaneous internal anterior pelvic ring
      fixation versus external pelvic ring fixation.
AB  - BACKGROUND: Although useful in the emergency treatment of pelvic ring injuries,
      external fixation is associated with pin tract infections, the patient's limited
      mobility and a restricted surgical accessibility to the lower abdomen. In this
      study, the mechanical stability of a subcutaneous internal anterior fixation
      (SIAF) system is investigated. METHODS: A standard external fixation and a SIAF
      system were tested on pairs of Polyoxymethylene testing cylinders using a
      universal testing machine. Each specimen was subjected to a total of 2000
      consecutive cyclic loadings at 1 Hz with sinusoidal lateral
      compression/distraction (+/-50 N) and torque (+/- 0.5 Nm) loading alternating
      every 200 cycles. Translational and rotational stiffness were determined at 100,
      300, 500, 700 and 900 cycles. RESULTS: There was no significant difference in
      translational stiffness between the SIAF and the standard external fixation when
      compared at 500 (p = .089), 700 (p = .081), and 900 (p = .266) cycles. Rotational
      stiffness observed for the SIAF was about 50 percent higher than the standard
      external fixation at 300 (p = .005), 500 (p = .020), and 900 (p = .005) cycles.
      No loosening or failure of the rod-pin/rod-screw interfaces was seen.
      CONCLUSIONS: In comparison with the standard external fixation system, the tested
      device for subcutaneous internal anterior fixation (SIAF) in vitro has similar
      translational and superior rotational stiffness.

PMID- 24684829
TI  - Lipoprotein(a) is associated with necrotic core progression of non-culprit
      coronary lesions in statin-treated patients with angina pectoris.
AB  - BACKGROUND: Statin therapy results in regression and stabilization of coronary
      artery plaques, and reduces the incidence of coronary artery disease. However,
      statin therapy does not effectively halt the accumulation of necrotic core in all
      patients. The purpose of the present study was to identify the predictors
      associated with necrotic core progression during statin therapy. METHODS:
      Coronary atherosclerosis in non-culprit lesions was evaluated using virtual
      histology intravascular ultrasound at baseline and 8 months after statin therapy.
      One hundred nineteen patients were divided into 2 groups based on necrotic core
      progression or regression during an 8-month follow-up period. RESULTS: Patients
      with necrotic core progression had higher serum lipoprotein(a) [Lp(a)] levels
      than patients with regression at baseline (16 mg/dL vs. 12 mg/dL, p = 0.02) and
      at the 8-month follow-up (17 mg/dL vs. 10 mg/dL, p = 0.006). Patients with
      necrotic core progression had a higher fibro-fatty plaque volume (1.28 mm3/mm vs.
      0.73 mm3/mm, p = 0.002), and less necrotic core (0.56 mm3/mm vs. 1.04 mm3/mm, p <
      0.0001) and dense calcium (0.35 mm3/mm vs. 0.56 mm3/mm, p = 0.006) plaque volumes
      at baseline than patients with regression. Multivariate logistic regression
      analysis showed that Lp(a) was a significant independent predictor associated
      with necrotic core progression during statin therapy (odds ratio [OR]: 3.514; 95%
      confidence interval [CI]: 1.338-9.228; p = 0.01). CONCLUSIONS: Serum Lp(a) is
      independently associated with necrotic core progression in statin-treated
      patients with angina pectoris.

PMID- 24684830
TI  - Functional genomic analysis of the periodic transcriptome in the developing
      Drosophila wing.
AB  - The eukaryotic cell cycle, driven by both transcriptional and posttranslational
      mechanisms, is the central molecular oscillator underlying tissue growth
      throughout animals. Although genome-wide studies have investigated cell-cycle
      associated transcription in unicellular systems, global patterns of periodic
      transcription in multicellular tissues remain largely unexplored. Here we define
      the cell-cycle-associated transcriptome of the developing Drosophila wing
      epithelium and compare it with that of cultured Drosophila S2 cells, revealing a
      core set of periodic genes and a surprising degree of context specificity in
      periodic transcription. We further employ RNAi-mediated phenotypic profiling to
      define functional requirements for more than 300 periodic genes, with a focus on
      those required for cell proliferation in vivo. Finally, we investigate
      uncharacterized genes required for interkinetic nuclear migration. Combined,
      these findings provide a global perspective on cell-cycle control in vivo, and
      they highlight a critical need to understand the context-specific regulation of
      cell proliferation.

PMID- 24684831
TI  - Genetic control of plant development by overriding a geometric division rule.
AB  - Formative cell divisions are critical for multicellular patterning. In the early
      plant embryo, such divisions follow from orienting the division plane. A major
      unanswered question is how division plane orientation is genetically controlled,
      and in particular whether this relates to cell geometry. We have generated a
      complete 4D map of early Arabidopsis embryogenesis and used computational
      analysis to demonstrate that several divisions follow a rule that uses the
      smallest wall area going through the center of the cell. In other cases, however,
      cell division clearly deviates from this rule, which invariably leads to
      asymmetric cell division. By analyzing mutant embryos and through targeted
      genetic perturbation, we show that response to the hormone auxin triggers a
      deviation from the "shortest wall" rule. Our work demonstrates that a simple
      default rule couples division orientation to cell geometry in the embryo and that
      genetic regulation can create patterns by overriding the default rule. 

PMID- 24684832
TI  - Use of probiotics in the treatment of severe acute pancreatitis: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Necrotic tissue infection can worsen the prognosis of severe acute
      pancreatitis (SAP), and probiotics have been shown to be beneficial in reducing
      the infection rate in animal experiments and primary clinical trials. However,
      the results of multicenter randomized clinical trials have been contradictory.
      Our aim in this study was to systematically review and quantitatively analyze all
      randomized controlled trials with regard to important outcomes in patients with
      predicted SAP who received probiotics. METHODS: A systematic literature search of
      the PubMed, Embase and Cochrane Library databases was conducted using specific
      search terms. Eligible studies were randomized controlled trials that compared
      the effects of probiotic with placebo treatment in patients with predicted SAP.
      Mean difference (MD), risk ratio (RR) and 95% confidence interval (95% CI) were
      calculated using the Mantel-Haenszel fixed- and random-effects models. A meta
      analysis on the use of probiotics in the treatment of critically ill patients was
      also performed to serve as a reference. RESULTS: In this study, 6 trials
      comprising an aggregate total of 536 patients were analyzed. Significant
      heterogeneities were observed in the type, dose, treatment duration and clinical
      effects of probiotics in these trials. Systematic analysis showed that probiotics
      did not significantly affect the pancreatic infection rate (RR = 1.19, 95% CI =
      0.74 to 1.93; P = 0.47), total infections (RR = 1.09, 95% CI = 0.80 to 1.48; P =
      0.57), operation rate (RR = 1.42, 95% CI = 0.43 to 3.47; P = 0.71), length of
      hospital stay (MD = 2.45, 95% CI = -2.71 to 7.60; P = 0.35) or mortality (RR =
      0.72, 95% CI = 0.42 to 1.45; P = 0.25). CONCLUSIONS: Probiotics showed neither
      beneficial nor adverse effects on the clinical outcomes of patients with
      predicted SAP. However, significant heterogeneity was noted between the trials
      reviewed with regard to the type, dose and treatment duration of probiotics,
      which may have contributed to the heterogeneity of the clinical outcomes. The
      current data are not sufficient to draw a conclusion regarding the effects of
      probiotics on patients with predicted SAP. Carefully designed clinical trials are
      needed to validate the effects of particular probiotics given at specific dosages
      and for specific treatment durations.

PMID- 24684833
TI  - The relationship between regional abdominal fat distribution and both insulin
      resistance and subclinical chronic inflammation in non-diabetic adults.
AB  - OBJECTIVE: Obesity is associated with a high risk of insulin resistance (IR) and
      its metabolic complications. It is still debated that distributions of adipose
      tissue relate to an excess risk of IR and chronic inflammation in different race.
      This study was designed to examine the relation between insulin sensitivity,
      chronic inflammation and central fat distribution in non-diabetic volunteers in
      Taiwanese. METHODS: There were 328 volunteers without family history of diabetes
      mellitus and with normal oral glucose tolerance test enrolled. Total body fat and
      abdominal fat were measured. Abdominal fat was categorized into intraperitoneal
      (IP), retroperitoneal (RP) and subcutaneous (SC) fat. The IR index was estimated
      by homeostatic model assessment. Five inflammatory markers: adiponectin, leptin,
      tumor necrosing factor-alpha (TNF-alpha), resistin and high sensitive CRP (hs
      CRP) were measured. RESULTS: IR was related to IP fat (r = 0.23, p < 0.001), but
      not RP fat, SC fat or total body fat. After correcting for age and sex, IP fat
      was the only significant predictor of IR (r2 = 58%, p = 0.001). Leptin showed the
      strongest relationship with all fat compartments (IP fat: r = 0.44, p = 0.001; RP
      fat: r = 0.36, p = 0.005, SC fat: r = 0.54, p < 0.001; total body fat: r = 0.61,
      p < 0.001). The hs-CRP and adiponectin were closely related both to IP (r = 0.29,
      p = 0.004; r = -0.20, p = 0.046, respectively) and total body fat (r = 0.29, p =
      0.004; r = -0.29, p = 0.005, respectively), but not RP, or SC fat. TNF-alpha and
      resistin were not correlated to any fat compartment. After correcting for age and
      sex, leptin variance was mostly explained by SC fat (41.3%), followed by IP fat
      (33.6%) and RP fat (25.3%). The hs-CRP and adiponectin variance were mostly
      explained by IP fat (40% and 49% respectively). CONCLUSIONS: IP fat is better
      predictors of IR and subclinical chronic inflammation in Taiwanese adults. A
      disproportionate accumulation of abdominal fat is associated with increased risk
      of cardiovascular diseases.

PMID- 24684834
TI  - Acute oxygenation changes on ischemic foot of a novel intermittent pneumatic
      compression device and of an existing sequential device in severe peripheral
      arterial disease.
AB  - BACKGROUND: Intermittent pneumatic compression (IPC) improves haemodynamics in
      peripheral arterial disease (PAD), but its effects on foot perfusion were
      scarcely studied. In severe PAD patients we measured the foot oxygenation changes
      evoked by a novel intermittent IPC device (GP), haemodynamics and compliance to
      the treatment. Reference values were obtained by a sequential foot-calf device
      (SFC). METHODS: Twenty ischemic limbs (Ankle-Brachial Index = 0.5 +/- 0.2) of 12
      PAD patients (7 male, age: 74.5 +/- 10.8 y) with an interval of 48 +/- 2 hours
      received a 35 minute treatment in supine position with two IPC devices: i) a
      Gradient Pump (GP), which slowly inflates a single thigh special sleeve and ii)
      an SFC (ArtAssist(r), ACI Medical, San Marcos, CA, USA), which rapidly inflates
      two foot-calf sleeves. MAIN OUTCOME MEASURE: changes of oxygenated haemoglobin at
      foot (HbO2foot) by continuous near-infrared spectroscopy recording and quantified
      as area-under-curve (AUC) for periods of 5 minutes. Other measures: haemodynamics
      by echo-colour Doppler (time average velocity (TAV) and blood flow (BF) in the
      popliteal artery and in the femoral vein), patient compliance by a properly
      developed form. RESULTS: All patients completed the treatment with GP, 9 with
      SFC. HbO2foot during the working phase, considered as average value of the 5
      minutes periods, increased with GP (AUC 458 +/- 600 to 1216 +/- 280) and
      decreased with SFC (AUC 231 +/- 946 to -1088 +/- 346), significantly for most
      periods (P < 0.05). The GP treatment was associated to significant haemodynamic
      changes from baseline to end of the treatment (TAV = 10.2 +/- 3.3 to 13.5 +/- 5.5
      cm/sec, P = 0.004; BF = 452.0 +/- 187.2 to 607.9 +/- 237.8 ml/sec, P = 0.0001),
      not observed with SFC (TAV = 11.2 +/- 3.4 to 11.8 +/- 4.3 cm/sec; BF  = 513.8 +/-
      203.7 to 505.9 +/- 166.5 ml/min, P = n.s.). GP obtained a higher score of patient
      compliance (P < 0.0001). CONCLUSIONS: A novel IPC thigh device, unlike a
      traditional SFC device, increased foot oxygenation in severe PAD, together with
      favourable haemodynamic response and high compliance to the treatment under the
      present experimental conditions.

PMID- 24684835
TI  - Epidemiological and molecular features of dengue virus type-1 in New Caledonia,
      South Pacific, 2001-2013.
AB  - BACKGROUND: The epidemiology of dengue in the South Pacific has been
      characterized by transmission of a single dominant serotype for 3-5 years, with
      subsequent replacement by another serotype. From 2001 to 2008 only DENV-1 was
      reported in the Pacific. In 2008, DENV-4 emerged and quickly displaced DENV-1 in
      the Pacific, except in New Caledonia (NC) where DENV-1 and DENV-4 co-circulated
      in 2008-2009. During 2012-2013, another DENV-1 outbreak occurred in NC, the third
      DENV-1 outbreak in a decade. Given that dengue is a serotype-specific immunizing
      infection, the recurrent outbreaks of a single serotype within a 10-year period
      was unexpected. FINDINGS: This study aimed to inform this phenomenon by examining
      the phylogenetic characteristics of the DENV-1 viruses in NC and other Pacific
      islands between 2001 and 2013. As a result, we have demonstrated that NC
      experienced introductions of viruses from both the Pacific (genotype IV) and
      South-east Asia (genotype I). Moreover, whereas genotype IV and I were co
      circulating at the beginning of 2012, we observed that from the second half of
      2012, i.e. during the major DENV-1 outbreak, all analyzed viruses were genotype I
      suggesting that a genotype switch occurred. CONCLUSIONS: Repeated outbreaks of
      the same dengue serotype, as observed in NC, is uncommon in the Pacific islands.
      Why the earlier DENV-1 outbreaks did not induce sufficient herd immunity is
      unclear, and likely multifactorial, but the robust vector control program may
      have played a role by limiting transmission and thus maintaining a large
      susceptible pool in the population.

PMID- 24684836
TI  - [Antifungal treatment for suspected or proved candidiasis in the critically ill].
AB  - OBJECTIVE: Describe systemic antifungal therapy in non-neutropenic adult patients
      in intensive care unit (ICU). PATIENTS AND METHOD: A prospective, observational
      study was conducted during the first half of 2010 in the 7 ICU in a hospital with
      medical consultant on antimicrobial therapy. All non-neutropenic consecutive
      adult patients receiving systemic antifungal therapy for documented or suspected
      invasive fungal infection (IFI) apart from aspergillosis were included. RESULTS:
      Out of 1502 patients admitted in ICU, 104 (7 %) underwent systemic antifungal
      therapy, including 30 (29 %) for a documented IFI and 74 (71 %) for a suspected
      IFI. Candida albicans was identified in 23 (77 %) of the IFI and 45/52 (86 %) of
      the broncho-pulmonary and/or urinary colonizations in suspected IFI. Echinocandin
      was significantly more prescribed in patients with a documented infection (19/30
      patients) and fluconazole in patients with a suspected infection (48/74
      patients). The first line therapy was primarily stopped after recovery (11/30
      patients) or de-escalation (9/30 patients) in documented infections, and for lack
      of indication (34/74 patients) or due to recovery (21/74 patients) in suspected
      infections after on average of 7 days of treatment. CONCLUSION: For ICU non
      neutropenic adult patients in our center, antifungal therapy is prescribed two
      times out of three for suspected, unproved infections, in most cases with
      fluconazole. Documented infections were more often treated by echinocandin with
      secondary de-escalation. An interventional prospective study to assess the role
      of antifungal pre-emptive or empirical therapy is necessary.

PMID- 24684837
TI  - Asthma linked with rhinosinusitis: An extensive review.
AB  - Current literature related to asthma diagnosis, epidemiology, pathogenesis, and
      treatment linked with rhinosinusitis is important. Asthma is very heterogeneous;
      new theories and treatments are emerging. It is a growing epidemic among children
      and adults in the United States and the severity of asthma is caused by many
      factors such as lack of education, poor early recognition, decreased symptom
      awareness, improper medications, and phenotypic changes. Genetic variation,
      innate immune genes, those involved in tissue remodeling and arachidonic acid
      metabolism, and inflammatory mediators might contribute to the pathogenesis of
      chronic rhinosinusitis (CRS) linked with asthma. This extensive review addresses
      concepts of the burden of asthma and sinusitis, altered innate immunity, adaptive
      immunity, asthma remodeling, the airway epithelium, the role of airway smooth
      muscle cells, united allergic airway, genetics, an integral part in asthma, and
      CRS. In addition, the role of vitamin D in both asthma and CRS in the elderly and
      pediatric population, various treatment options, and exhaled nitric oxide are
      briefly addressed. 

PMID- 24684838
TI  - Morphologic parameters relevant for visual outcome during anti-angiogenic therapy
      of neovascular age-related macular degeneration.
AB  - PURPOSE: To identify the effects of anti-angiogenic therapy in neovascular age
      related macular degeneration (AMD) in respect to morphologic type and time course
      and to identify prognostic factors for visual outcome on the basis of
      standardized optical coherence tomography (OCT) analysis. DESIGN: Subanalysis of
      a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of
      Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to
      Age-Related Macular Degeneration [EXCITE]). PARTICIPANTS: A total of 353
      treatment-naive patients with subfoveal choroidal neovascularization (CNV)
      receiving quarterly or monthly ranibizumab therapy. METHODS: Patients were
      randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses
      of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly
      injections followed by a 9-month maintenance phase of monthly or quarterly
      injections. Best-corrected visual acuity (BCVA) was measured using the Early
      Treatment Diabetic Retinopathy Study protocol, and retinal morphology was
      assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were
      evaluated by certified examiners of the Vienna Reading Center using a
      standardized protocol. MAIN OUTCOME MEASURES: The BCVA was measured using ETDRS
      charts and retinal morphology was assessed by OCT. RESULTS: During the loading
      phase, there was a significant correlation between a reduction in central retinal
      thickness and an increase in BCVA (P < 0.001), which decreased during the
      maintenance phase in all treatment arms. The proportion of patients showing
      retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid
      (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all
      groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg
      groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED
      decreased at a slower rate and intensity. Patients with IRC at baseline had lower
      BCVA levels that remained lower over the entire study period, whereas recurrence
      of IRC during follow-up showed no additional negative effect on function.
      Baseline SRF had no effect on visual recovery; however, recurrence of SRF during
      follow-up showed a tendency for an additional negative effect on function (P =
      0.06). Baseline PED showed a negative influence on visual outcome only in
      combination with IRC and SRF. CONCLUSIONS: There is a distinct response pattern
      and time course of morphologic parameters associated with anti-vascular
      endothelial growth factor therapy in neovascular AMD. Specific alterations, such
      as IRC, SRF, and PED, as baseline or follow-up features are significantly
      influencing the potential for visual gain.

PMID- 24684839
TI  - Low seroprevalence of systemic cysticercosis among patients with epilepsy in
      Kerala--South India.
AB  - PURPOSE: Neurocysticercosis (NCC) is considered to be rare in Kerala state,
      India, although it is an important cause of epilepsy in many other parts of
      India. Our objective was to test this notion by determining the seroprevalence of
      cysticercosis (CC) in an unselected sample of persons with epilepsy and comparing
      it to that of persons without epilepsy living in Kerala. METHODS: Individuals
      with active epilepsy (AE) who had never resided outside Kerala state for more
      than one month and were attending our center for epilepsy care constituted the
      cases. Sex-matched persons without epilepsy who had never resided outside Kerala
      state for more than one month constituted the controls. The demographic details,
      occupation, and food habits (for the cases and controls), as well as clinical
      characteristics and imaging (for cases only) were recorded. Sera separated from
      blood drawn by venipuncture from the cases and controls were assayed for
      cysticercal antibodies by enzyme-linked immunoelectrotransfer blot (EITB).
      RESULTS: Of the 80 persons with AE, 12 were seropositive for cysticercus
      antibodies (15%; 95% CI: 8.8-24.4); among the 68 controls, 7 were seropositive
      (10.3%; 95% CI: 5.1-19.8). The odds ratio (OR) for seropositivity in the epilepsy
      group (1.54) was not statistically significant (95% CI: 0.6-4.2). Among the 69
      patients who had a brain computed tomography (CT) scan or magnetic resonance
      imaging (MRI), none had features diagnostic of NCC. Gender, diet (vegetarian vs
      non-vegetarian, consumption of raw vegetables), drinking water status (clean vs
      unclean), residence (rural vs urban), exposure to manure, and animal rearing
      including pigs did not have any association with seropositivity. CONCLUSION:
      Among the residents of Kerala, most epilepsy is not related to cysticercosis.

PMID- 24684840
TI  - Multisubstituted indole-acrylonitrile hybrids as potential cytotoxic agents.
AB  - A series of multisubstituted indole-acrylonitrile hybrids were designed,
      synthesized and evaluated for their potential cytotoxic activities. The bio
      evaluation results indicated that some of the target compounds (such as 3a, 3f,
      3k, 3n) exhibited good to moderate cytotoxic effect on HepG2, BCG-823, BEL-7402,
      and HL-7702 cell lines. Especially, the compounds 3a and 3k also exhibited high
      cytotoxic activities (3a, 19.38+/-3.38 MUM; 3k, 15.43+/-3.54 MUM) against the BEL
      7402 cell line resistant to Taxol (>25MUM) and 5-FU (>500 MUM), which might be
      developed as novel lead scaffold for potential anticancer agents.

PMID- 24684841
TI  - Naphthalene-hydrophobized beta-1,3-glucan nanogel for doxorubicin delivery to
      immunocytes.
AB  - A water soluble beta-1,3-glucan schizophyllan (SPG) can be recognized by an
      immunocyte receptor called dectin-1. When we introduced naphthalene into the side
      chain of SPG (nSPG), it formed nanogel by physical cross-link and gained
      capability to ingest hydrophobic compounds such as doxorubicin. Our in vitro
      assay revealed that this nanogel can be used as specific delivery of anti-cancer
      drugs to immunocytes. 

PMID- 24684842
TI  - Design, synthesis, and biological evaluation of dihydroartemisinin
      fluoroquinolone conjugates as a novel type of potential antitubercular agents.
AB  - Tuberculosis remains a global public health problem in recent years. To develop
      novel type of potential antitubercular agents, twelve novel dihydroartemisinin
      fluoroquinolone (DHA-FQ) conjugates (three types of molecules) were gradually
      designed and conveniently synthesized. All the newly synthesized conjugates were
      well characterized and evaluated against different Mycobacterium tuberculosis
      strains in vitro. The screening results showed that five DHA-FQ conjugates were
      active toward M. tuberculosis H37Rv, and compound 3a exhibited the strongest
      inhibitory activity (MIC=0.0625 MUg/mL), which was comparable to the positive
      control Moxifloxacin and even stronger than Ofloxacin. Conjugates 2a and 3a also
      displayed comparable activities against various clinically isolated sensitive and
      resistant M. tuberculosis strains (MIC=0.125-16 MUg/mL) to Moxifloxacin. All
      target compounds possessed selective anti-M. tuberculosis ability. Preliminary
      structure-activity relationship demonstrated that short linker between DHA and FQ
      was favorable for strong antitubercular activity. This study provides a new clue
      for the development of novel antitubercular lead molecules.

PMID- 24684843
TI  - In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the
      treatment of glaucoma.
AB  - A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo
      activity for topical ocular dosing. Modifications of the 2-(piperazin-1
      yl)pyrazine derivatives produced compounds with improved solubility and
      physicochemical properties. Modifications of the 6-pyrazine substituent led to
      improvements in in vitro potency. Compound 9 had the best in vitro and in vivo
      potency of EC50=260 nM with a 30% reduction of IOP in a non-human primate model
      at a dose of 0.33%.

PMID- 24684844
TI  - Spiramine derivatives induce apoptosis of Bax(-/-)/Bak(-/-) cell and cancer
      cells.
AB  - Spiramine C-D, the atisine-type diterpenoid alkaloids isolated from the Chinese
      herbal medicine Spiraea japonica complex, are shown to have anti-inflammatory
      effects in vitro. In this study, we report that spiramine derivatives of
      spiramine C-D bearing alpha,beta-unsaturated ketone induce apoptosis of Bax(-/
      )/Bak(-/-) MEFs cell, which is positively corresponding their cytotoxicity of
      tumor cell lines including multidrug resistance MCF-7/ADR. The results indicated
      that oxazolidine ring is necessary, and derivatives bearing double 'Michael
      reaction acceptor' group would significantly increased activities both of
      inducing apoptosis of Bax(-/-)/Bak(-/-) cells and cytotoxicity of tumor cells.
      The result indicated that spiramine derivative with alpha,beta-unsaturated ketone
      group is a new anti-cancer agent with a capability of inducing apoptosis of
      cancer cells in Bax/Bak-independent manner. 

PMID- 24684845
TI  - Synthesis and biological evaluation of novel bis-aromatic amides as novel PTP1B
      inhibitors.
AB  - A series of bis-aromatic amides was designed, synthesized, and evaluated as a new
      class of inhibitors with IC50 values in the micromolar range against protein
      tyrosine phosphatase 1B (PTP1B). Among them, compound 15 displayed an IC50 value
      of 2.34+/-0.08 MUM with 5-fold preference over TCPTP. More importantly, the
      treatment of CHO/HIR cells with compound 15 resulted in increased phosphorylation
      of insulin receptor (IR), which suggested extensive cellular activity of compound
      15. These results provided novel lead compounds for the design of inhibitors of
      PTP1B as well as other PTPs.

PMID- 24684847
TI  - Dual function of p38alpha MAPK in colon cancer: suppression of colitis-associated
      tumor initiation but requirement for cancer cell survival.
AB  - Colorectal cancer is frequently associated with chronic inflammation, with the
      intestinal epithelial barrier playing an important protective role against the
      infections and injuries that cause colitis. The p38alpha pathway regulates
      inflammatory responses but can also suppress tumor initiation in epithelial
      cells. We have found that p38alpha signaling has a dual function in colorectal
      tumorigenesis. On one side, p38alpha protects intestinal epithelial cells against
      colitis-associated colon cancer by regulating intestinal epithelial barrier
      function. Accordingly, p38alpha downregulation results in enhanced colitis
      induced epithelial damage and inflammation, which potentiates colon tumor
      formation. Surprisingly, inhibition of p38alpha in transformed colon epithelial
      cells reduces tumor burden. Thus, p38alpha suppresses inflammation-associated
      epithelial damage and tumorigenesis but contributes to the proliferation and
      survival of tumor cells. 

PMID- 24684848
TI  - [Non-medical applications for brain MRI: Ethical considerations].
AB  - INTRODUCTION: The recent neuroimaging techniques offer the possibility to better
      understand complex cognitive processes that are involved in mental disorders and
      thus have become cornerstone tools for research in psychiatry. The performances
      of functional magnetic resonance imaging are not limited to medical research and
      are used in non-medical fields. These recent applications represent new
      challenges for bioethics. OBJECTIVE: In this article we aim at discussing the new
      ethical issues raised by the applications of the latest neuroimaging technologies
      to non-medical fields. METHODS: We included a selection of peer-reviewed English
      medical articles after a search on NCBI Pubmed database and Google scholar from
      2000 to 2013. We screened bibliographical tables for supplementary references.
      Websites of governmental French institutions implicated in ethical questions were
      also screened for governmental reports. RESULTS: Findings of brain areas
      supporting emotional responses and regulation have been used for marketing
      research, also called neuromarketing. The discovery of different brain activation
      patterns in antisocial disorder has led to changes in forensic psychiatry with
      the use of imaging techniques with unproven validity. Automated classification
      algorithms and multivariate statistical analyses of brain images have been
      applied to brain-reading techniques, aiming at predicting unconscious neural
      processes in humans. We finally report the current position of the French
      legislation recently revised and discuss the technical limits of such techniques.
      DISCUSSION: In the near future, brain imaging could find clinical applications in
      psychiatry as diagnostic or predictive tools. However, the latest advances in
      brain imaging are also used in non-scientific fields raising key ethical
      questions. Involvement of neuroscientists, psychiatrists, physicians but also of
      citizens in neuroethics discussions is crucial to challenge the risk of
      unregulated uses of brain imaging.

PMID- 24684846
TI  - Pemetrexed and gemcitabine as combination therapy for the treatment of Group3
      medulloblastoma.
AB  - We devised a high-throughput, cell-based assay to identify compounds to treat
      Group3 medulloblastoma (G3 MB). Mouse G3 MBs neurospheres were screened against a
      library of approximately 7,000 compounds including US Food and Drug
      Administration-approved drugs. We found that pemetrexed and gemcitabine
      preferentially inhibited G3 MB proliferation in vitro compared to control
      neurospheres and substantially inhibited G3 MB proliferation in vivo. When
      combined, these two drugs significantly increased survival of mice bearing
      cortical implants of mouse and human G3 MBs that overexpress MYC compared to each
      agent alone, while having little effect on mouse MBs of the sonic hedgehog
      subgroup. Our findings strongly suggest that combination therapy with pemetrexed
      and gemcitabine is a promising treatment for G3 MBs.

PMID- 24684849
TI  - Rotavirus infections, vaccines and virus variability.

PMID- 24684850
TI  - Association of APOA5 rs662799 and rs3135506 polymorphisms with arterial
      hypertension in Moroccan patients.
AB  - BACKGROUND: The goal of the study is to investigate the association between the
      APOA5 polymorphisms and haplotypes with Arterial Hypertension (AHT) in Moroccan
      patients. METHODS: The study was performed in 283 subjects, 149 patients with AHT
      and 134 controls. All subjects were genotyped for the APOA5 -1131 T > C
      (rs662799), 56C > G (rs3135506) and c.553G > T (rs2075291) polymorphisms.
      RESULTS: There was a strong association between -1131 T > C and 56C > G
      polymorphisms with AHT. The -1131 T > C and 56C > G polymorphisms were
      significantly associated with increased systolic blood pressure (SBP) and
      triglycerides (TG) levels. There were 4 haplotypes with a frequency higher than
      5%, constructed from APOA5 polymorphisms, with the following order: -1131 T > C,
      56C > G and c.553G > T. Haplotype H1 (TCG) was associated with decreased risk of
      AHT, whereas the haplotypes H2 (CCG) and H4 (CGG) were significantly associated
      with an increased risk of AHT. Carriers of H1 haplotype had a lower SBP and DBP
      and TG. In contrast, significant elevated SBP, DBP and TG were found in H4
      haplotypes carriers. CONCLUSIONS: Our data demonstrate for the first time that
      several common SNPs in the APOA5 gene and their haplotypes are closely associated
      with modifications of blood pressure and serum lipid parameters in the AHT
      patient.

PMID- 24684851
TI  - Cardiovascular polypharmacy is not associated with unplanned hospitalisation:
      evidence from a retrospective cohort study.
AB  - BACKGROUND: Polypharmacy is often considered suggestive of suboptimal
      prescribing, and is associated with adverse outcomes. It is particularly common
      in the context of cardiovascular disease, but it is unclear whether prescribing
      of multiple cardiovascular medicines, which may be entirely appropriate and
      consistent with clinical guidance, is associated with adverse outcome. The aim of
      this study was to assess the relationship between number of prescribed
      cardiovascular medicines and unplanned non-cardiovascular hospital admissions.
      METHODS: A retrospective cohort analysis of 180,815 adult patients was conducted
      using Scottish primary care data linked to hospital discharge data. Patients were
      followed up for one year for the outcome of unplanned non-cardiovascular hospital
      admission. The association between number of prescribed cardiovascular medicines
      and hospitalisation was modelled using logistic regression, adjusting for key
      confounding factors including cardiovascular and non-cardiovascular morbidity and
      non-cardiovascular prescribing. RESULTS: 25.4% patients were prescribed >=1
      cardiovascular medicine, and 5.7% were prescribed >=5. At least one unplanned non
      cardiovascular admission was experienced by 4.2% of patients. Admissions were
      more common in patients receiving multiple cardiovascular medicines (6.4% of
      patients prescribed 5 or 6 cardiovascular medicines) compared with those
      prescribed none (3.5%). However, after adjusting for key confounders,
      cardiovascular prescribing was associated with fewer non-cardiovascular
      admissions (OR 0.66 for 5 or 6 vs. no cardiovascular medicines, 95% CI 0.57
      0.75). CONCLUSIONS: We found no evidence that increasing numbers of
      cardiovascular medicines were associated with an increased risk of unplanned non
      cardiovascular hospitalisation, following adjustment for confounding. Assumptions
      that polypharmacy is hazardous and represents poor care should be moderated in
      the context of cardiovascular disease.

PMID- 24684852
TI  - Knowledge brokering in public health: a tale of two studies.
AB  - OBJECTIVES: A Knowledge Broker is one approach for facilitating the integration
      of evidence-informed decision making in public health practice. In this paper,
      the findings from two studies investigating a Knowledge Broker intervention as a
      means of enhancing capacity for evidence-informed decision making are presented.
      Contextual factors that facilitate this strategy are also identified. STUDY
      DESIGN: This paper describes work done through a single mixed-methods study
      (randomized controlled trial with a qualitative component) and a case study.
      METHODS: The Health Evidence team conducted two studies examining Knowledge
      Broker impact in Canadian public health departments. The effectiveness of
      knowledge translation strategies of varying intensities for promoting the use of
      research evidence in decisions related to child obesity prevention were explored
      via a randomized controlled trial with a fundamental descriptive component (2003
      2007). In a case study (2010-2013), the authors partnered with three health
      departments to develop and implement tailored strategies targeted at the
      organization. Knowledge Brokers worked with designated staff in these studies via
      one-on-one consultations, small group meetings, and/or workshops and
      presentations. The Knowledge Broker role was assessed by analysing data from
      close-ended surveys, interviews, organizational documents, and reflective
      journals. RESULTS: In this paper, the authors focus on findings from the
      qualitative analysis of implementing the Knowledge Broker role in both studies
      and explore several contextual factors that impacted study outcomes. Knowledge
      Brokers were shown to enhance individual capacity by improving knowledge and
      skill in searching for, critically appraising, and applying research evidence to
      practice-based issues. Organizational capacity was also enhanced with strong
      management support and policies. Effective Knowledge Broker attributes included
      both expertise in research methodology and public health, as well as intangible
      traits such as approachability and patience. Finally, optimal positioning and
      ways of working were identified, including the importance of in-person meetings
      and neutrality of the Knowledge Broker. CONCLUSIONS: Knowledge brokering is a
      potentially promising knowledge translation strategy for public health, though
      additional feasibility and cost-effectiveness data are still needed. The research
      presented here further highlights the importance of context and adopting a
      tailored approach to implement a Knowledge Broker strategy.

PMID- 24684853
TI  - Cardiovascular and metabolic responses to tap water ingestion in young humans:
      does the water temperature matter?
AB  - AIM: Drinking water induces short-term cardiovascular and metabolic changes.
      These effects are considered to be triggered by gastric distension and osmotic
      factors, but little is known about the influence of water temperature. METHODS:
      We determined, in a randomized crossover study, the acute cardiovascular and
      metabolic responses to 500 mL of tap water at 3  degrees C (cold), 22  degrees C
      (room) and 37  degrees C (body) in 12 young humans to ascertain an effect of
      water temperature. We measured continuous beat-to-beat haemodynamics, skin blood
      flux with laser-Doppler flowmetry and resting energy expenditure by indirect
      calorimetry starting with a 30-min baseline followed by a 4-min drink period and
      a subsequent 90-min post-drink observation. RESULTS: Ingestion of cold- and room
      tempered water led to decreased heart rate (P < 0.01) and double product (P <
      0.01), and increased stroke volume (P < 0.05); these effects were not observed
      with body-tempered water. Drinking cold- and room-, but not body-tempered water,
      led to increased high frequency power of heart rate variability (P < 0.05) and
      baroreflex sensitivity (P < 0.05). Cold- and room-tempered water increased energy
      expenditure over 90 min by 2.9% (P < 0.05) and 2.3% (ns), respectively,
      accompanied by a diminished skin blood flux (P < 0.01), thereby suggesting that
      both small increases in heat production together with decreased heat loss
      contribute to warming up the ingested water to intra-abdominal temperature
      levels. CONCLUSIONS: Overall, ingestion of cold- and room-, but not body-tempered
      water reduced the workload to the heart through a reduction in heart rate and
      double product which could be mediated by an augmented cardiac vagal tone.

PMID- 24684854
TI  - Mise en place: setting the stage for thought and action.
AB  - A school became safer after security measures were removed. Children can learn
      better in playful, rather than didactic, settings. At-risk students earned higher
      grades after writing about a personal value. A novel construct - mise en place-
      explains how small changes in context, such as these, can lead to large changes
      in behaviors by highlighting how the psychology of preparing to act within an
      environment shapes and is shaped by that environment.

PMID- 24684855
TI  - Contemporary use of beta-blockers: clinical relevance of subclassification.
AB  - beta-Adrenergic receptor blockers or beta-blockers represent one of the oldest
      classes of cardiovascular agents and have been considered a cornerstone therapy
      for hypertension and heart disease for the past 5 decades. They are advocated as
      a first-line treatment for uncomplicated essential hypertension in patients
      younger than 60 years of age as recommended by the Canadian Hypertension
      Education Program. However, despite the well-established antihypertensive and
      cardiovascular benefits of beta-blockers, a number of studies argue that they
      might not have the same clinical advantages of other classes of agents in terms
      of morbidity/mortality outcomes. This review will focus on the heterogeneity of
      the pharmacologic characteristics of beta-blockers, and we will discuss the
      metabolic and hemodynamic differences within the beta-blocker class and try to
      assess the potential implications of these differences for optimal selection in
      hypertension. 

PMID- 24684856
TI  - A single fixed-dose combination for all patients is bad medicine.
AB  - It has been proposed that cardiovascular risk could be markedly reduced by
      prescribing a single daily pill to all patients at risk. This concept is bad
      medicine, because each constituent has problems, and the problems are different
      for each patient. A key principle of clinical pharmacology is individualization
      of therapy. Patients are not all the same, so a single polypill cannot work for
      all of them. For patients with resistant hypertension, at least 3 different
      versions would be needed for patients with different causes of hypertension, and
      even then not one pill would be suitable for all patients. 

PMID- 24684857
TI  - A multicentric evaluation of the recombinant Leishmania infantum antigen-based
      immunochromatographic assay for the serodiagnosis of canine visceral
      leishmaniasis.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a serious public health challenge in
      Brazil and dogs are considered to be the main urban reservoir of the causative
      agent. The culling of animals to control VL in some countries makes the accurate
      diagnosis of canine VL (CVL) essential. Recombinant antigens rLci1A and rLci2B
      were selected from a cDNA library of Leishmania infantum amastigotes due to their
      strong potential as candidates in diagnostic testing for CVL. The present
      multicentric study aimed to evaluate the sensitivity of a prototype test using
      these antigens (DPP rLci1A/rLci2B) against 154 sera obtained from symptomatic
      dogs within three endemic areas of VL in Brazil. The specificity was evaluated
      using 40 serum samples from negative dogs and dogs infected with other pathogens.
      Sensitivity and specificity rates of DPP rLci1A/rLci2B prototype were compared to
      rates from other diagnostic tests currently in use by the Brazilian Ministry of
      Health, including DPPLVC, EIELVC. FINDINGS: DPP rLci1A/rLci2B prototype offered
      similar performance to that offered by DPPLVC rapid test, as follows: sensitivity
      of 87% (CI 81-91) and 88% (CI 82-93) and specificity of 100% (CI 91-100) and 97%
      (CI 87-100), respectively for DPP rLci1A/rLci2B and DPPLVC. When results of these
      two tests were considered concomitantly, sensitivity increased to 93.5% (CI 89
      96). CONCLUSIONS: The recombinant antigens rLci1A and rLci2B represent promising
      candidates for use in a multi-antigen rapid test for CVL. The inclusion of novel
      antigens to the DPP rLci1A/rLci2B prototype model could offer additionally
      enhanced sensitivity to detect animals infected by L. infantum.

PMID- 24684858
TI  - Tongue pressure during swallowing is decreased in patients with Duchenne muscular
      dystrophy.
AB  - Although dysphagia is a life-threatening problem in patients with Duchenne
      muscular dystrophy (DMD), the pathophysiology of oral stage dysphagia is yet to
      be understood. The present study investigated the tongue motor deficit during
      swallowing in patients with DMD and its relationship with disease-specific
      palatal morphology. Tongue pressure during swallowing water was recorded in 11
      male patients with DMD and 11 age- and sex-matched healthy subjects using an
      intra-oral sensor with five measuring points, and the state of tongue pressure
      production was compared between the groups. Palatal morphology was assessed by a
      non-contact three-dimensional scanner on maxillary plaster models. In patients
      with DMD, the normal sequential order of tongue-palate contact was lost and the
      maximal magnitude and integrated value of tongue pressure on the mid-anterior
      part of palate were smaller than those in healthy subjects. The width of the
      palate in patients was greater than that in healthy subjects and the depth of the
      palate in patients had a negative correlation with tongue pressure magnitude on
      the median palate. Our results suggested that the deteriorated tongue motor
      kinetics prevented tongue movement during swallowing that was appropriate for the
      depth of the palate and affects the state of tongue pressure production during
      swallowing. 

PMID- 24684859
TI  - Congenital muscular dystrophy with dropped head phenotype and cognitive
      impairment due to a novel mutation in the LMNA gene.
AB  - Mutations in A-type nuclear lamins are known to cause a variety of diseases,
      which can affect almost all organs of the human body including striated muscle.
      For lamin-related congenital muscular dystrophy two different phenotypes are
      known to date. Here, we describe a 3-year-old, white Caucasian girl with a novel
      de novo mutation in the LMNA gene with marked hypotonia of neck and trunk muscles
      with dropped head posture, loss of cervical lordosis and marked joint laxity. In
      addition to this novel mutation, the patient also had cerebral white matter
      lesions on MRI and cognitive impairment on developmental testing. This is only
      the second A-type lamin-related congenital muscular dystrophy patient in which
      white matter lesions are described. Thus, white matter involvement might be a
      feature in A-type lamin-related congenital muscular dystrophy, warranting
      screening of these patients for both white matter lesions and cognitive
      impairment. 

PMID- 24684860
TI  - Anti-gravity training improves walking capacity and postural balance in patients
      with muscular dystrophy.
AB  - Recent studies in patients with muscular dystrophies suggest positive effects of
      aerobic and strength training. These studies focused training on using bicycle
      ergometers and conventional strength training, which precludes more severely
      affected patients from participating, because of their weakness. We investigated
      the functional effects of combined aerobic and strength training in patients with
      Becker and limb-girdle muscular dystrophies with knee muscle strength levels as
      low as 3% of normal strength. Eight patients performed 10 weeks of aerobic and
      strength training on an anti-gravity treadmill, which offered weight support up
      to 80% of their body weight. Six minute walking distance, dynamic postural
      balance, and plasma creatine kinase were assessed 10 weeks prior to training,
      immediately before training and after 10 weeks of training. Training elicited an
      improvement of walking distance by 8+/-2% and dynamic postural balance by 13+/
      4%, indicating an improved physical function. Plasma creatine kinase remained
      unchanged. These results provide evidence that a combination of aerobic and
      strength training during anti-gravity has the potential to safely improve
      functional ability in severely affected patients with Becker and limb-girdle
      muscular dystrophies.

PMID- 24684861
TI  - Activation of the PKR/eIF2alpha signaling cascade inhibits replication of
      Newcastle disease virus.
AB  - BACKGROUND: Newcastle Disease virus (NDV) causes severe and economically
      significant disease in almost all birds. However, factors that affect NDV
      replication in host cells are poorly understood. NDV generates long double
      stranded RNA (dsRNA) molecules during transcription of single-stranded genomic
      RNA. Protein kinase R (PKR) is activated by dsRNA. The aim of this study was to
      elucidate the role of PKR in NDV infection. RESULTS: NDV infection led to the
      activation of dsRNA-dependent PKR and phosphorylation of its substrate,
      translation initiation factor eIF2alpha, in a dose-dependent manner by either the
      lentogenic strain LaSota or a velogenic strain Herts/33. PKR activation coincided
      with the accumulation of dsRNA induced by NDV infection. PKR knockdown remarkably
      decreased eIF2alpha phosphorylation as well as IFN-beta mRNA levels, leading to
      the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or
      phosphorylation of eIF2alpha or okadaic acid treatment significantly impaired NDV
      replication, indicating the critical role of the PKR/eIF2alpha signaling cascade
      in NDV infection. CONCLUSION: PKR is activated by dsRNA generated by NDV
      infection and inhibits NDV replication by eIF2alpha phosphorylation. This study
      provides insight into NDV-host interactions for the development of candidate
      antiviral strategies.

PMID- 24684862
TI  - Comments on: "Intraoperative neurophysiologic monitoring in spine surgery.
      Developments and state of the art in France in 2011" written by M. Gavaret et al.
      published in Orthop Traumatol Surg Res 2013;99:s319-27.

PMID- 24684863
TI  - Percutaneous pelvic osteotomy in non-ambulatory cerebral palsy patients.
AB  - The aim of this study was to describe the surgical technique of and indications
      for percutaneous pelvic osteotomy in patients with severe cerebral palsy. Forty
      non-ambulatory children and adolescents (47 hips) were consecutively treated with
      percutaneous pelvic osteotomy. The mean preoperative Reimers' migration
      percentage improved from 66.2% to 4.9% at the final follow-up. The mean
      preoperative acetabular angle (AA) improved from 32.4 degrees  to 13.2 degrees 
      at last follow-up. Percutaneous pelvic osteotomy is a less invasive surgical
      approach and appears to be a valid option with similar outcomes to standard
      techniques.This method results in less muscle stripping and blood loss and a
      shorter operating time. 

PMID- 24684864
TI  - Patterns and predictors of osteoporosis medication discontinuation and switching
      among Medicare beneficiaries.
AB  - BACKGROUND: Low adherence to bisphosphonate therapy is associated with increased
      fracture risk. Factors associated with discontinuation of osteoporosis
      medications have not been studied in-depth. This study assessed medication
      discontinuation and switching patterns among Medicare beneficiaries who were new
      users of bisphosphonates and evaluated factors possibly associated with
      discontinuation. METHODS: We identified patients initiating bisphosphonate
      treatment using a 5% random sample of Medicare beneficiaries with at least 24
      months of traditional fee-for-service and part D drug coverage from 2006 through
      2009. We classified medication status at the end of follow-up as: continued
      original bisphosphonate, discontinued without switching or restarting, restarted
      the same drug after a treatment gap (>= 90 days), or switched to another anti
      osteoporosis medication. We conducted logistic regression analyses to identify
      baseline characteristics associated with discontinuation and a case-crossover
      analysis to identify factors that precipitate discontinuation. RESULTS: Of 21,452
      new users followed respectively for 12 months, 44% continued their original
      therapy, 36% discontinued without switching or restarting, 8% restarted the same
      drug after a gap greater than 90 days, and 11% switched to another anti
      osteoporosis medication. Factors assessed during the 12-month period before
      initiation were weakly associated with discontinuation. Several Factors measured
      during follow-up were associated with discontinuation, including more physician
      visits, hospitalization, having a dual-energy X-ray absorptiometry test, higher
      Charlson comorbidity index scores, higher out-of-pocket drug payments, and upper
      gastrointestinal problems. Patterns were similar for 4,738 new users followed for
      30 months. CONCLUSIONS: Among new bisphosphonates users, switching within and
      across drug classes and extended treatment gaps are common. Robust definitions
      and time-varying considerations should be considered to characterize medication
      discontinuation more accurately.

PMID- 24684865
TI  - Vaccine risk assessment in children with a referred reaction to a previous
      vaccine dose: 2009-2011 retrospective report at the Bambino Gesu' children
      hospital, Rome, Italy.
AB  - BACKGROUND: During the last century, mass vaccination programs have achieved
      considerable success across the world in immunizing against several serious
      infectious diseases. However, vaccinations are threatened by their own success
      after results have been obtained: the more the incidence of potentially
      devastating diseases decreases, thanks to the success of vaccination programs,
      the more public attention shifts towards real or alleged "side effects" of
      vaccines. METHODS: We analyze the experience of 153 children with "reaction to a
      previous vaccine dose" continuing the vaccination protocol in the safe
      environment of the Center for risk vaccination at the Bambino Gesu Children's
      Hospital IRCCS in Rome, from 2009 to 2011. RESULTS: To assess the suitability for
      vaccination, a specialized pre-vaccination advice and a skin prick test (SPT) was
      undergone, according to Wood's guideline; 151 children were SPT negative and full
      vaccine was administered. Of the 153 children examined just 13 had symptoms
      suggestive of IgE-mediated reaction-type reactions with angioedema
      manifestations. Among them, 2 had positive STP, which required alternative
      measures of administration of the vaccine. No cases of post vaccination reaction
      was reported and no vaccination program was stopped due to a severe reaction.
      CONCLUSIONS: Inadequate levels of immunization against infectious diseases remain
      a significant problem for public health. However, the reasons for incomplete
      vaccination and non-adoption of vaccination services are manifold. To maintain
      public confidence in vaccines, advanced immunization programs must include
      activities for monitoring the safety of the vaccine at the individual level and
      pursuing specialized counseling pre-and post-vaccination for those at risk. Our
      results underlined a gap between true and referred adverse reactions and are
      consistent with vaccine safety. Anyway, a continuous assessment of the risks and
      benefits of vaccination is required and the results must be disclosed in order to
      strengthen confidence in the existing and in the new immunization programs.

PMID- 24684867
TI  - A prospective, randomized controlled trial of single-incision laparoscopic vs
      conventional 3-port laparoscopic appendectomy for treatment of acute
      appendicitis.
AB  - BACKGROUND: Proponents of single-incision laparoscopic surgery (SILS) claim
      patients have less pain, faster recovery, and better long-term cosmetic results
      than patients who undergo multiport laparoscopy. However, randomized comparisons
      are lacking. This study presents the results of a prospective randomized trial of
      SILS or 3-port laparoscopic appendectomy. STUDY DESIGN: Adults with uncomplicated
      acute appendicitis were randomized 1:1 to either SILS or 3-port laparoscopic
      appendectomy. The primary end point was early postoperative pain (measured by
      opiate usage and pain score in the first 12 hours). Secondary end points were
      operative time, complication rate (including conversions), and recovery time
      (days of oral opiate usage and return to work). After 6 months, body image and
      cosmetic appearance were assessed using a validated survey. RESULTS: The trial
      was planned for 150 patients, but was halted after 75 patients when planned
      interim analysis showed that SILS patients had more postoperative pain (pain
      score: 4.4 +/- 1.6 vs 3.5 +/- 1.5; p = 0.01) and higher inpatient opiate usage
      (hydromorphone use: 3.9 +/- 1.9 mg vs 2.8 +/- 1.7 mg; p = 0.01) than 3-port
      laparoscopy. Operative time for SILS averaged 40% longer (54 +/- 17 minutes vs 38
      +/- 11 minutes; p < 0.01). Only 1 SILS case was converted to 3-port. There were
      no significant differences in length of stay, complications, oral pain medication
      usage after discharge, or return to work. After 6 months, body image and cosmetic
      appearance were excellent for both groups and indistinguishable by most measures.
      However, 3-port patients reported better physical attractiveness (4.0 +/- 0.4 vs
      3.8 +/- 0.4; p = 0.04) and SILS patients reported better scars (score 18.4 +/-
      2.7 vs 16.4 +/- 3.0; p < 0.01). Results are reported as mean +/- SD. CONCLUSIONS:
      Single-incision laparoscopic surgery appendectomy resulted in more pain and
      longer operative times without improving short-term recovery or complications.
      Long-term body image and cosmetic appearance were excellent in both groups.

PMID- 24684868
TI  - The usefulness of preoperative biopsy in unilateral nasal masses.
AB  - Unilateral nasal masses are considered suspicious for proliferative diseases.
      Several tools are routinely used to investigate unilateral lesions such as
      imaging and nasal biopsy. This study investigated the usefulness of nasal biopsy
      in predicting the actual nature of unilateral lesions. Preoperative nasal biopsy
      pathological results were compared with the final pathology obtained during an
      operation. Forty-six patients with unilateral nasal masses were included in the
      study group. In 40 patients the final pathology was similar to the preoperative
      nasal biopsy. In three patients the biopsy specimen was a benign polyp and the
      final pathology was of an inverted papilloma in two patients and
      hemangiopericytoma in one patient. In two patients the biopsy specimen was
      suspicious for an inverted papilloma and the final pathology was a benign polyp.
      In one patient the biopsy specimen was chordoma and the final pathology was
      osteosarcoma. The total agreement was 86.9%. The kappa value was 81.2%.
      Preoperative nasal biopsy is important and useful in evaluating unilateral nasal
      masses. 

PMID- 24684869
TI  - FT-IR, FT-Raman spectra, and DFT computations of the vibrational spectra and
      molecular geometry of chlorzoxazone.
AB  - Far-IR, mid-IR, and FT-Raman spectra of the chlorzoxazone (CZX) were recorded.
      The observed vibrational wavenumbers were analyzed and assigned to different
      normal modes of vibration of the molecule. Density functional calculations were
      performed to support wavenumber assignments of the observed bands. The
      equilibrium geometry and harmonic wavenumbers of CZX were calculated by the DFT
      B3LYP method. All tautomeric forms and dimer form of CZX were determined and
      optimized. Additionally, experimental FT-IR spectrum in ethanol solution was
      recorded and compared with solid phase experimental data for the first time. The
      combination of the DFT B3LYP with polarized continuum model (PCM) was employed to
      characterize the solvent effects in ethanol solution. 

PMID- 24684871
TI  - What is ahead for Mayo Clinic?

PMID- 24684870
TI  - Melanoma resistance: a bright future for academicians and a challenge for patient
      advocates.

PMID- 24684872
TI  - Cardiac and multiorgan transplantation for end-stage congenital heart disease.
AB  - OBJECTIVE: To report our single-center experience with patients who had cardiac
      and multiorgan transplantation for end-stage congenital heart disease (CHD).
      PATIENTS AND METHODS: We reviewed records for all patients with CHD who had
      undergone heart transplantation at Mayo Clinic, Rochester, Minnesota, from
      November 1, 1990, through June 30, 2012. Patients with cardiomyopathy were
      excluded, unless CHD was present. RESULTS: Overall, 45 patients had cardiac
      transplantation for end-stage CHD (mean age, 26.1+/-18.4 years; range, 1 month to
      65 years). Two patients (4%) had combined heart/liver transplantation; 1 (2%) had
      heart/kidney transplantation. Six patients (13%) had no previous cardiac
      operation; the remaining 39 patients had a mean of 3 (range, 1-8) previous
      cardiac operations. Patient survival (95% CI) at 1, 5, and 10 years was 89% (80%
      98%), 89% (80%-98%), and 72% (56%-87%), respectively, while graft survival at 1,
      5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 61% (44%-78%),
      respectively. During the same era, the International Society for Heart & Lung
      Transplantation reported that survival in patients undergoing transplant for non
      congenital diagnoses was 85%, 72%, and 56%, respectively. Over a mean follow-up
      of 8.7+/-6.2 years, rejection requiring treatment was documented in 35 patients
      (78%). Eleven patients (24%) have been diagnosed with neoplasia (8 skin, 1 blood,
      1 lymph, and 1 other), and 3 patients (7%) have required retransplantation. Four
      patients (9%) have developed significant coronary vasculopathy; 1 successfully
      underwent retransplantation, and 3 died 6, 8, and 14 years after transplantation.
      CONCLUSION: With appropriate patient selection and posttransplant monitoring,
      survival has improved for patients with complex end-stage CHD. Multiorgan
      transplantation is an option for selected patients with CHD.

PMID- 24684873
TI  - Latest advances in chemotherapeutic, targeted, and immune approaches in the
      treatment of metastatic melanoma.
AB  - Melanoma is the most dangerous form of skin cancer owing to its metastatic
      potential and is an important public health concern. The melanoma incidence has
      been increasing worldwide. Although potentially curable when diagnosed early,
      metastatic melanoma carries a poor prognosis. Until recently, systemic therapy
      for metastatic melanoma was ineffective, but the recent successes in the
      development of new therapies for metastatic melanoma, such as mitogen-activated
      protein kinase (MAPK) pathway inhibitors, anti-cytotoxic T-lymphocyte-associated
      antigen-4 (CTLA-4), and programmed cell death protein 1 (PD-1)/programmed cell
      death ligand 1 (PD-L1) pathway blocking antibodies, as well as combination
      strategies of cytotoxic chemotherapy and inhibitors of angiogenesis, have all
      yielded promising results, changing the continually evolving landscape of
      therapeutic options for patients with this disease. The aim of this review was to
      summarize the evolution of and recent advances in the treatment of metastatic
      melanoma. Therefore, we conducted a comprehensive PubMed search between January
      1, 1960, and February 1, 2014, using the search term melanoma or metastatic
      melanoma combined with terms such as chemotherapy, immunotherapy, CTLA-4, PD-1,
      PD-L1, adoptive T cell, targeted therapy, MAPK, molecular biology, and survival.

PMID- 24684875
TI  - Diagnosis and management of benign, atypical, and indeterminate breast lesions
      detected on core needle biopsy.
AB  - Imaging abnormalities detected by mammographic screening often lead to diagnostic
      evaluations, with suspicious abnormalities subjected to image-guided core needle
      biopsy (CNB) to exclude malignancy. Most CNBs reveal benign pathological
      alterations, termed benign breast disease (BBD). Adoption of CNB presents
      challenges with pathologic classification of breast abnormalities and management
      of patients with benign or atypical histological findings. Patient management and
      counseling after CNB diagnosis of BBD depends on postbiopsy determination of
      radiologic-pathologic concordancy. Communication between radiologists and
      pathologists is crucial in patient management. Management is dependent on the
      histological type of BBD. Patients with concordant pathologic imaging results can
      be reassured of benign biopsy findings and advised about the future risk of
      developing breast cancer. Surgical consultation is advised for patients with
      discordant findings, symptomatic patients, and high-risk lesions. This review
      highlights benign breast lesions that are encountered on CNB and summarizes
      management strategies. For this review, we conducted a search of PubMed, with no
      date limitations, and used the following search terms (or a combination of
      terms): atypical ductal hyperplasia, atypical hyperplasia, atypical lobular
      hyperplasia, benign breast disease, cellular fibroepithelial lesions, columnar
      cell lesions, complex sclerosing lesion, core needle biopsy, fibroadenomas, flat
      epithelial atypia, lobular carcinoma in situ, lobular neoplasia, mucocele-like
      lesions, phyllodes tumor, pseudoangiomatous stromal hyperplasia, radial scar, and
      vascular lesions. The selection of references included in this review was based
      on study relevance and quality. We used additional articles culled from the
      bibliographies of retrieved articles to examine the published evidence for risk
      factors of BBD.

PMID- 24684876
TI  - Breast density and breast cancer risk: a practical review.
AB  - New legislation in several states requiring breast density notification in all
      mammogram reports has increased awareness of breast density. Estimates indicate
      that up to 50% of women undergoing mammography will have high breast density;
      thus, with increased attention and high prevalence of increased breast density,
      it is crucial that primary care clinicians understand the implications of dense
      breasts and are able to provide appropriate counseling. This review provides an
      overview of breast density, specifically by defining breast density, exploring
      the association between breast density and breast cancer risk, both from masking
      and as an independent risk factor, and reviewing supplemental screening options
      as part of a larger framework for counseling patients with dense breasts.

PMID- 24684877
TI  - 37-year-old man with abdominal pain.

PMID- 24684879
TI  - Is coffee harmful? If looking for longevity, say yes to the coffee, no to the
      sugar.

PMID- 24684874
TI  - Immunomodulatory effects of sex hormones: requirements for pregnancy and
      relevance in melanoma.
AB  - Similarities between the pathologic progression of cancer and the physiologic
      process of placentation (eg, proliferation, invasion, and local/systemic
      tolerance) have been recognized for many years. Sex hormones such as human
      chorionic gonadotropin, estrogens, progesterone, and others contribute to
      induction of immunologic tolerance at the beginning of gestation. Sex hormones
      have been shown to play contributory roles in the growth of cancers such as
      breast cancer, prostrate cancer, endometrial cancer, and ovarian cancer, but
      their involvement as putative mediators of the immunologic escape of cancer is
      still being elucidated. Herein, we compare the emerging mechanism by which sex
      hormones modulate systemic immunity in pregnancy and their potentially similar
      role in cancer. To do this, we conducted a PubMed search using combinations of
      the following keywords: "immune regulation," "sex hormones," "pregnancy,"
      "melanoma," and "cancer." We did not limit our search to specific publication
      dates. Mimicking the maternal immune response to pregnancy, especially in late
      gestation, might aid in design of better therapies to reconstitute endogenous
      antitumor immunity and improve survival.

PMID- 24684880
TI  - In reply--is coffee harmful? If looking for longevity, say yes to the coffee, no
      to the sugar.

PMID- 24684878
TI  - Targets of immune regeneration in rheumatoid arthritis.
AB  - Many of the aging-related morbidities, including cancer, cardiovascular disease,
      neurodegenerative disease, and infectious susceptibility, are linked to a decline
      in immune competence with a concomitant rise in proinflammatory immunity, placing
      the process of immune aging at the center of aging biology. Immune aging affects
      individuals older than 50 years and is accelerated in patients with the
      autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline
      in protective immune responses and a parallel increase in tissue inflammatory
      responses. By studying immune cells in patients with rheumatoid arthritis,
      several of the molecular underpinnings of the immune aging process have been
      delineated, such as the loss of telomeres and inefficiencies in the repair of
      damaged DNA. Aging T cells display a series of abnormalities, including the
      unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic
      competence, that alter their response to stimulating signals and undermine their
      longevity. Understanding the connection between accelerated immune aging and
      autoimmunity remains an area of active research. With increasing knowledge of the
      molecular pathways that cause immunosenescence, therapeutic interventions can be
      designed to slow or halt the seemingly inevitable deterioration of protective
      immunity with aging.

PMID- 24684881
TI  - Testicular microlithiasis.

PMID- 24684882
TI  - Physician-poet William Carlos Williams--"no ideas but in things".

PMID- 24684884
TI  - Long-term recurrence rates following excision and cartilage rim shave of
      chondrodermatitis nodularis chronica helicis and antihelicis.

PMID- 24684885
TI  - Placenta increta originating from placental remnants of a first trimester
      vanished twin.

PMID- 24684886
TI  - Dry season refugia for anopheline larvae and mapping of the seasonal distribution
      in mosquito larval habitats in Kandi, northeastern Benin.
AB  - BACKGROUND: The dynamics of mosquito populations depends on availability of
      suitable surface water for oviposition. It is well known that suitable management
      of mosquito larval habitats in the sub-Saharan countries, particularly during
      droughts, could help to suppress vector densities and malaria transmission. We
      conducted a field survey to investigate the spatial and seasonal distribution of
      mosquito larval habitats and identify drought-refugia for anopheline larvae.
      METHODS: A GIS approach was used to identify, geo-reference and follow up
      longitudinally from May 2012 to May 2013, all mosquito breeding sites in two
      rural sites (Yondarou and Thui), one urban (Kossarou), and one peri-urban (Pede)
      site at Kandi, a municipality in northeastern Benin. In Kandi, droughts are
      excessive with no rain for nearly six months and a lot of sunshine. A
      comprehensive record of mosquito larval habitats was conducted periodically in
      all sites for the identification of drought-refugia of anopheline larval stages.
      With geospatialisation data, seasonal larval distribution maps were generated for
      each study site with the software ArcGIS version 10.2. RESULTS: Overall, 187
      mosquito breeding sites were identified of which 29.95% were recorded during
      drought. In rural, peri-urban and urban sites, most of the drought-refugia of
      anopheline larvae were domestic in nature (61.54%). Moreover, in rural settings,
      anopheline larvae were also sampled in cisterns and wells (25% of larval habitats
      sampled during drought in Yondarou and 20% in Thui). The mapping showed a
      significant decrease in the spatial distribution of mosquito larval habitats in
      rural, peri-urban and urban sites during drought, except in Yondarou (rural)
      where the aridity did not seem to influence the distribution of larval habitats.
      CONCLUSION: Our data showed that the main drought-refugia of anopheline larvae
      were of a domestic nature as well as wells and cisterns. A suitable management of
      mosquito larvae in sub-Saharan countries, particularly during droughts, should
      target such larval habitats for a meaningful impact on the dynamics of mosquito
      populations and malaria transmission.

PMID- 24684887
TI  - [Spontaneous Listeria monocytogenes bacterial peritonitis].

PMID- 24684888
TI  - [Spondylodiscitis due to Clostridium perfringens].

PMID- 24684889
TI  - Analysis of emergency department consults with an on-call neurologist due to
      seizures.

PMID- 24684890
TI  - Visual hallucinations related to use of ertapenem.

PMID- 24684891
TI  - Skeletal metastases in 301 breast cancer patients: patient survival and
      complications after surgery.
AB  - The aim was to identify prognostic variables associated with survival in 301
      breast cancer patients after surgical treatment of skeletal metastases. The study
      period was 1986-2012. The median age at surgery was 61 (interquartile-range [IQR]
      52-70) years. The cumulative 1-, 2-, and 5-year survival after surgery was 45%
      (95% CI 39-51), 27% (22-32), and 8% (5-12), respectively. The median follow-up
      time was 1 (IQR 0.2-2) year. Age over 60 years (Hazard ratio [HR] 1.9) and
      hemoglobin levels <110 g/L (HR 2) increased the risk of death after surgery.
      Patients with impending fractures (HR 0.4) had a lower death rate. The overall
      neurological function in patients with spinal metastases improved after surgery
      (p < 0.001). The complication rate was 25%, including 14% re-operations. Survival
      data and analysis of complications of this large cohort of surgically treated
      breast cancer patients help to set appropriate expectations for the patients,
      families, and medical staff. 

PMID- 24684892
TI  - Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic
      murine inhalation models.
AB  - BACKGROUND: Although ZnO nanoparticles (NPs) are used in many commercial products
      and the potential for human exposure is increasing, few in vivo studies have
      addressed their possible toxic effects after inhalation. We sought to determine
      whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub
      chronic inhalation exposure to realistic exposure doses. METHODS: Mice (C57Bl/6)
      were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub
      acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3
      wks) post exposure. Toxicity was assessed by enumeration of total and
      differential cells, determination of total protein, lactate dehydrogenase
      activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well
      as measurements of pulmonary mechanics. Generation of reactive oxygen species was
      assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn
      content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL
      fluid was measured. RESULTS: An elevated concentration of Zn2+ was detected in
      BAL fluid immediately after exposures, but returned to baseline levels 3 wks post
      exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial
      lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial
      interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of
      macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1alpha,
      but no other inflammatory or toxic responses were observed. Following both sub
      acute and sub-chronic exposures, pulmonary mechanics were no different than sham
      exposed animals. CONCLUSIONS: Our ZnO NP inhalation studies showed minimal
      pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated
      concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in
      the respiratory system after inhalation. Exposure concentration, exposure mode
      and time post exposure played an important role in the toxicity of ZnO NPs.
      Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung
      cellularity, but other markers of toxicity did not differ from sham-exposed
      animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by
      the inhalation route.

PMID- 24684893
TI  - Sequence variability in the structural protein-encoding region of foot-and-mouth
      disease virus serotype A and O of Ethiopian isolates.
AB  - A total of 13 serotype O and 5 serotype A FMD Ethiopian isolates and some
      isolates from other countries (six for serotype A and four for serotype O) were
      sequenced on the structural protein (P1) coding region. The deduced amino acid
      sequences were aligned and investigated in an attempt to determine the amino acid
      variation. Differences were observed at 115 (15.6%) and 119 (16.1%) amino acid
      positions for serotype O and serotype A, respectively. The variation in the
      derived amino acid sequences is the highest in VP1, while VP4 was highly
      conserved in both serotypes A and O. In all isolates, hypervariable regions were
      located at regions corresponding to the highly immunogenic sites, the G-H loop
      (133-158) and the C-terminus (194-213) of the VP1 gene. The RGD cell attachment
      site within the G-H loop of the gene was conserved in all isolates. The study
      revealed the presence of significant amino acid variation at VP2 and VP3 in
      addition to known VP1 coding region. Hence, determination of amino acid sequence
      of the whole P1 region provides more information on antigenic variability of FMD
      virus and could be used in vaccine strain selection in parallel with serological
      vaccine matching assays.

PMID- 24684894
TI  - Doppler velocimetric parameters of the testicular artery in healthy dogs.
AB  - This study aimed to examine the Doppler velocimetric pattern of the testicular
      artery of small dogs in two different locations. Testes of 21 dogs were evaluated
      by two-dimensional ultrasonography to measure testicular volume and by Doppler
      ultrasonography to record the velocimetric patterns of the testicular artery in
      the spermatic cord and marginal location. The volume of left testes (4.70 +/-
      1.22 cm(3)) was significantly higher than the volume of the right testes (4.45 +/
      1.17 cm(3)). Peak systolic velocity (PSV) of the left spermatic cord was
      significantly higher than the right side. End-diastolic velocity was
      significantly higher in the marginal artery than the spermatic cord on both
      sides; however, resistance and pulsatility indexes were significantly lower in
      the marginal artery. Results demonstrate the viability of Doppler ultrasonography
      for characterization of the testicular artery in small dogs and Doppler
      velocimetric values vary according to the location of measurement along the
      artery.

PMID- 24684895
TI  - Evaluation of biomarkers for osteoarthritis caused by fragmented medial coronoid
      process in dogs.
AB  - The aim of the present work was to evaluate whether concentrations of the carboxy
      terminal cross-linked fragment of type II collagen (CTX-II), the activities of
      matrix metalloproteinase-2 and -9 (MMP-2/-9) and Myeloperoxidase (MPO) in canine
      synovial fluids (SF) can reflect structural alterations of articular cartilage in
      dogs with fragmented medial coronoid process (FMCP). Elbow joints with FMCP
      underwent radiographic and arthroscopic examination. Commercially available
      assays were used to analyze SF for CTX-II concentration and MMP-2/-9 activity.
      MPO activity was measured by o-dianisidine-assay. The MMPs were further evaluated
      by zymography. CTX-II concentration and MMP-2 activity showed age-dependent
      trends in controls. Increased enzyme activities of MPO and MMP-2/-9 were found in
      diseased dogs. MMP-9activity seems suitable to underline the subjective
      assessment of the degree of cartilage damage. These initial data of the study
      suggest that MPO and MMP-2/9 may be used as objective biomarkers in the diagnosis
      of canine osteoarthritis due to FMCP.

PMID- 24684897
TI  - Functional characterisation of human pulmonary monocyte-like cells in
      lipopolysaccharide-mediated acute lung inflammation.
AB  - BACKGROUND: We have previously reported the presence of novel subpopulations of
      pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA
      DR(+)CD14(++)CD16(+)cells) and inducible PMLC (iPMLC, HLA-DR(+)CD14(++)CD16(-)
      cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid
      following inhalation of lipopolysaccharide (LPS). We have carried out the first
      functional evaluation of PMLC subpopulations in the inflamed lung, following the
      isolation of these cells, and other lineages, from BAL fluid using novel and
      complex protocols. METHODS: iPMLC, rPMLC, alveolar macrophages (AM), neutrophils,
      and regulatory T cells were quantified in BAL fluid of healthy subjects at 9
      hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC,
      rPMLC and AM and the ability of each lineage to proliferate and to undergo
      phagocytosis were investigated using flow cytometry. Basal cytokine production by
      iPMLC compared to AM following their isolation from BAL fluid and the
      responsiveness of both cell types following in vitro treatment with the synthetic
      corticosteroid dexamethasone were assessed. RESULTS: rPMLC have a significantly
      increased expression of mature macrophage markers and of the proliferation
      antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory,
      corticosteroid-resistant phenotype of iPMLC in this model. CONCLUSIONS: These
      data emphasise the presence of functionally distinct subpopulations of the
      monocyte/macrophage lineage in the human lung in experimental acute lung
      inflammation.

PMID- 24684896
TI  - Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case
      report.
AB  - Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly
      presents with symptoms and signs of catecholamine excess, such as hypertension,
      tachycardia, headache and sweating. Cardiovascular manifestations include
      catecholamine-induced cardiomyopathy, which may present as severe left
      ventricular dysfunction and congestive heart failure. We report a case of
      pheochromocytoma which was diagnosed following investigation of dilated
      cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of
      cardiomyopathy, with recovery of left ventricular function after treatment. 

PMID- 24684898
TI  - High prevalence of Helicobacter pylori infection in Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a multisystem disease of unknown etiology.
      There are several clues which may indicate an ethiopathogenesis role for
      Helicobacter pylori infection in this disease. METHODS: In a case control study
      in an out patient department, 48 patients with BD were compared to age, sex
      matched controls regarding presence of H. pylori infection by serology and urea
      breath test (UBT). RESULTS: Ongoing H. pylori infection was more prevalent among
      patients with BD using result of UBT with odds ratio of 3.1 (95% CI: 1.34 - 7.26,
      PV < 0.001). CONCLUSION: H. pylori infection may have a role in the pathogenesis
      of BD.

PMID- 24684899
TI  - Familial malignant mesothelioma: a population-based study in central Italy (1980
      2012).
AB  - Malignant mesothelioma is a sporadic cancer linked to asbestos exposure. Its
      occurrence among blood relatives (familial mesothelioma) may point to genetic
      susceptibility or shared exposures. The burden of the familial disease is
      unknown. The aims of the study were to assess at population level the proportion
      of familial mesotheliomas among all mesotheliomas and to investigate the family
      history of cancer among relatives of mesothelioma cases. We actively searched
      familial clusters based on a mesothelioma registry from central Italy (5.5
      million people, 10% of the Italian population) of the National Mesothelioma
      Register network (ReNaM) as well as a pathology-based archive. Among 997 incident
      mesotheliomas recorded in a 32-year-period (1980-2012), we detected 13 clusters
      and 34 familial cases, accounting for 3.4% of all mesotheliomas. The most common
      clusters where those with affected siblings and unaffected parents. Asbestos
      exposure was occupational (n=7 clusters), household (n=2), environmental (n=1),
      or not attributable for insufficient information (n=3). There were 25 additional
      cancers in nine families. Some were cancer sites for which there is sufficient
      evidence (lung and larynx) or limited evidence (stomach and colon) of causal
      association with asbestos. The results suggest potential genetic recessive
      effects in mesothelioma that interact with asbestos exposure, but it is not
      possible to estimate the specific proportion attributable to each of these
      components. 

PMID- 24684900
TI  - Professional meetings: what's missing?

PMID- 24684901
TI  - Effect of governmental intervention on appropriateness of lumbar MRI referrals: a
      Canadian experience.
AB  - PURPOSE: In 2012, the Ontario government attempted to reduce inappropriate lumbar
      MRI referrals through guideline and decision-aid distributions to physicians as
      well as threats of financial penalties. The goals of this study were to determine
      if any change in lumbar MRI referral appropriateness occurred after this policy
      change at a tertiary care hospital in Ontario and to determine if any change in
      the number of new lumbar MRI referrals occurred after the policy change. METHODS:
      Six hundred lumbar MRI referral forms were randomly selected; 300 before and 300
      after the policy change. The ACR Appropriateness Criteria for low back pain
      imaging were used to evaluate the appropriateness of each referral and assign it
      a score from 1 to 9. The numbers of new referrals during 3-month periods both
      before and after the policy change were recorded. Student's t test was performed
      to test for significant differences after the policy change. RESULTS: Before the
      policy change, 50.4% of lumbar MRI referrals were appropriate, and 47.9% were not
      appropriate. After the policy change, appropriateness increased, with 62.6% of
      referrals being appropriate and 37.1% not appropriate. The mean appropriateness
      score before the policy change was 5.08 (95% confidence interval, 4.74-5.42) and
      increased significantly after the policy change to 5.79 (95% confidence interval,
      5.46-6.12) (P = .004). No significant difference in the number of new lumbar MRI
      referrals before (246 +/- 20.1 per month) and after (232.7 +/- 38.3 per month)
      the policy change was noted (P > .05). CONCLUSIONS: The Ontario government's
      interventions have significantly increased the appropriateness of lumbar MRI
      referrals. However, many referrals remain inappropriate, and no change in the
      number of new referrals has occurred.

PMID- 24684902
TI  - Radiology trainees' comfort with difficult conversations and attitudes about
      error disclosure: effect of a communication skills workshop.
AB  - PURPOSE: The aim of this study was to assess the effect of communication skills
      training on radiology trainees' (1) comfort with communicating directly with
      patients and family members about unexpected or difficult diagnoses ("bad news"),
      radiologic errors, and radiation risks and (2) attitudes about disclosing
      radiologic errors directly to patients and their families. METHODS: One hundred
      nine radiology trainees from 16 US programs were asked to complete questionnaires
      immediately before and after attending an institutional review board-exempted,
      full-day communication workshop. Questionnaires assessed (1) comfort
      communicating with patients and their families generally and about bad news,
      radiologic errors, and radiation risks specifically; (2) attitudes and behavioral
      intent regarding a hypothetical vignette involving a radiologic error; and (3)
      desire for additional communication training. RESULTS: All trainees completed the
      questionnaires. After completing the workshop, more trainees reported comfort
      communicating with patients about bad news, errors, and radiation risks (pre vs
      post, 44% vs 73%, 25% vs 44%, and 34% vs 58%, respectively, P < .001 for all).
      More also agreed that the radiologist in the error vignette should discuss the
      error with the patient (pre vs post, 84% vs 95%; P = .002) and apologize (pre vs
      post, 78% vs 94%; P < .001). After participation, fewer trainees reported
      unwillingness to disclose the error despite medicolegal concerns (pre vs post, 39
      vs 15%; P < .001). Despite high baseline comfort (92%) and low stress (14%)
      talking with patients in general, most respondents after participation desired
      additional communication training on error disclosure (83%), general
      communication (56%), and radiation risks (80%). CONCLUSIONS: This program
      provides effective communication training for radiology trainees. Many trainees
      desire more such programs.

PMID- 24684903
TI  - Preexisting cognitive status is associated with reduced behavioral functional
      capacity in patients 3 months after cardiac surgery: an extension study.
AB  - OBJECTIVE: To examine whether preexisting cognitive status rather than short- and
      middle-term postoperative cognitive decline (POCD) may differentially account for
      behavioral functional capacity 3 months after cardiac surgery. METHOD: Seventy
      nine patients completed a psychological evaluation, including the Trail Making
      Test Part B, the memory with 10-s interference, the phonemic fluency and the
      Instrumental Activities of Daily Living (IADLs) questionnaire for cognitive
      functions and behavioral functional capacity, respectively, before surgery, at
      discharge and at 3-month follow-up. RESULTS: Thirty-one (39%) and 22 (28%)
      patients showed POCD at discharge and at 3-month follow-up, respectively.
      Preoperative cognitive status was significantly associated with change in
      behavioral functional capacity 3 months after surgery (Ps<.003), whereas short-
      and middle-term POCD and intraoperative risk factors were unrelated to
      residualized change in IADLs scores (all Ps>.095). CONCLUSIONS: Preexisting
      cognitive deficit, especially working memory deficit, rather than short- and
      middle-term POCD related to intraoperative risk factors is associated with poor
      behavioral functional capacity 3 months after cardiac surgery. The present study
      therefore suggests that a preoperative cognitive evaluation is essential to
      anticipate which patients are likely to show a decline in behavioral functional
      capacity after cardiac surgery.

PMID- 24684904
TI  - Simultaneous multi-analyte urinary protein assay for bladder cancer detection.
AB  - BACKGROUND: The ability to accurately measure multiple proteins simultaneously in
      a single assay has the potential to markedly improve the efficiency of a myriad
      of clinical assays. Here, we tested the performance of a new, multiplex protein
      array platform to quantitate three bladder cancer-associated proteins in urine
      samples. The following analytes, interleukin 8 (IL8), matrix metallopeptidase 9
      (MMP9), and vascular endothelial growth factor A (VEGFA) were monitored using Q
      plex, a customized multiplex ELISA system from Quansys Biosciences, and
      individual target commercial ELISA kits. The performance of the two approaches
      was compared by evaluating the diagnostic accuracy of the biomarker assays in
      samples from a cohort of 73 subjects of known bladder cancer status. RESULTS: The
      combination biomarker panel analyses revealed an AUROC value of 0.9476 for the Q
      plex assay, and 0.9119 for the combination of the single-target ELISA assays. The
      Q-plex assay achieved an overall diagnostic sensitivity of 0.93 and specificity
      of 0.81, and the individual target ELISA assays achieved an overall sensitivity
      of 0.77 and specificity of 0.91. CONCLUSION: Based on these encouraging
      preliminary data, we believe that the Q-Plex technology is a viable platform that
      can be exploited as an efficient, highly accurate tool to quantitate multiplex
      panels of diagnostic proteins in biologic specimens.

PMID- 24684905
TI  - Neural crest development and craniofacial morphogenesis is coordinated by nitric
      oxide and histone acetylation.
AB  - Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences
      that undergo convergence and extension to generate the craniofacial form. We
      applied a chemical genetics approach to identify pathways that regulate
      craniofacial development during embryogenesis. Treatment with the nitric oxide
      synthase inhibitor 1-(2-[trifluoromethyl] phenyl) imidazole (TRIM) abrogated
      first pharyngeal arch structures and induced ectopic ceratobranchial formation.
      TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation,
      which were mediated through impaired nitric oxide (NO) production without
      appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox
      gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was
      achieved with overexpression of histone acetyltransferase kat6a, inhibition of
      histone deacetylase, and complementary NO. These studies demonstrate that NO
      signaling and histone acetylation are coordinated mechanisms that regulate CNC
      patterning, differentiation, and convergence during craniofacial morphogenesis. 

PMID- 24684906
TI  - Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium
      tuberculosis by targeting the ATP-dependent protease ClpC1P1P2.
AB  - Languishing antibiotic discovery and flourishing antibiotic resistance have
      prompted the development of alternative untapped sources for antibiotic
      discovery, including previously uncultured bacteria. Here, we screen extracts
      from uncultured species against Mycobacterium tuberculosis and identify
      lassomycin, an antibiotic that exhibits potent bactericidal activity against both
      growing and dormant mycobacteria, including drug-resistant forms of M.
      tuberculosis, but little activity against other bacteria or mammalian cells.
      Lassomycin is a highly basic, ribosomally encoded cyclic peptide with an unusual
      structural fold that only partially resembles that of other lasso peptides. We
      show that lassomycin binds to a highly acidic region of the ClpC1 ATPase complex
      and markedly stimulates its ATPase activity without stimulating ClpP1P2-catalyzed
      protein breakdown, which is essential for viability of mycobacteria. This
      mechanism, uncoupling ATPase from proteolytic activity, accounts for the
      bactericidal activity of lassomycin. 

PMID- 24684907
TI  - A zebrafish chemical suppressor screening identifies small molecule inhibitors of
      the Wnt/beta-catenin pathway.
AB  - Genetic screening for suppressor mutants has been successfully used to identify
      important signaling regulators. Using an analogy to genetic suppressor screening,
      we developed a chemical suppressor screening method to identify inhibitors of the
      Wnt/beta-catenin signaling pathway. We used zebrafish embryos in which chemically
      induced beta-catenin accumulation led to an "eyeless" phenotype and conducted a
      pilot screening for compounds that restored eye development. This approach
      allowed us to identify geranylgeranyltransferase inhibitor 286 (GGTI-286), a
      geranylgeranyltransferase (GGTase) inhibitor. Our follow-up studies showed that
      GGTI-286 reduces nuclear localization of beta-catenin and transcription dependent
      on beta-catenin/T cell factor in mammalian cells. In addition to pharmacological
      inhibition, GGTase gene knockdown also attenuates the nuclear function of beta
      catenin. Overall, we validate our chemical suppressor screening as a method for
      identifying Wnt/beta-catenin pathway inhibitors and implicate GGTase as a
      potential therapeutic target for Wnt-activated cancers. 

PMID- 24684909
TI  - Dynamic soft tissue balancing in total knee arthroplasty.
AB  - Achieving optimal soft tissue balance intraoperatively is a critical element for
      a successful outcome after total knee arthroplasty. Although advances in
      navigation have improved the incidence of angular outliers, spatial distance
      measurements do not quantify soft tissue stability or degrees of ligament
      tension. Revisions caused by instability, malrotation, and malalignment still
      constitute up to one-third of early knee revisions. The development of integrated
      microelectronics and sensors into the knee trials during surgery allows surgeons
      to evaluate and act on real-time data regarding implant position, rotation,
      alignment, and soft tissue balance through a full range of motion. 

PMID- 24684908
TI  - Molecular and chemical characterization of the biosynthesis of the 6-MSA-derived
      meroterpenoid yanuthone D in Aspergillus niger.
AB  - Secondary metabolites in filamentous fungi constitute a rich source of bioactive
      molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic
      yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a
      meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA).
      Yanuthone D formation depends on a cluster composed of ten genes including yanA
      and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O
      mevalon transferase, respectively. In addition, several branching points in the
      pathway were discovered, revealing five yanuthones (F, G, H, I, and J).
      Furthermore, we have identified another compound (yanuthone X1) that defines a
      class of yanuthones that depend on several enzymatic activities encoded by genes
      in the yan cluster but that are not derived from 6-MSA. 

PMID- 24684910
TI  - Total knee arthroplasty with a novel navigation system within the surgical field.
AB  - Total knee arthroplasty is a common procedure, and current navigation systems are
      gradually gaining acceptance for improving surgical accuracy and clinical
      outcomes. A new navigation system used within the surgical field, iAssist, has
      demonstrated reproducible accuracy in component alignment. All orientation
      information is captured by small electronic pods and transmitted via a local
      wireless network, which directs the surgical workflow automatically to the
      femoral and tibial resection instruments. This simple and accurate navigation
      system used completely in the surgical field, without optical trackers or
      preoperative imaging, seems to be the latest generation of smart instrumentation
      for total knee arthroplasty. 

PMID- 24684911
TI  - Soft tissue balance in total knee arthroplasty with a force sensor.
AB  - This article presents a concise description and literature review of the eLibra
      Dynamic Ligament Balancing Device in total knee arthroplasty. This device is a
      force sensor that allows surgeons to balance the medial and lateral collateral
      ligaments during total knee replacement. This instrument provides precise,
      quantitative, digital information in newtons during surgery that allows surgeons
      to accurately externally rotate the femoral component in order to balance the
      forces across the medial and lateral compartments. The device is highly accurate
      and simple to use. It relies on objective dynamic data to balance the knee rather
      than static landmarks or subjective tensiometers. 

PMID- 24684912
TI  - Handheld navigation in total knee arthroplasty.
AB  - Computer navigation for knee replacement surgery has been available for over a
      decade but has not gained popularity despite improved accuracy. The literature
      has shown higher failure rates for knee replacements with tibial malalignment.
      This article reviews some of this literature and demonstrates a novel handheld,
      simple-to-use, disposable navigation system that has been proven to be accurate
      and may be the answer to combining ease of use, lower cost, and increased
      accuracy to give better overall results. 

PMID- 24684913
TI  - Principles of tibial fracture management with circular external fixation.
AB  - There is a growing mass of literature to suggest that circular external fixation
      for high-energy tibial fractures has advantages over traditional internal
      fixation, with potential improved rates of union, decreased incidence of
      posttraumatic osteomyelitis, and decreased soft tissue problems. To further
      advance our understanding of the role of circular external fixation in the
      management of these tibial fractures, randomized controlled trials should be
      implemented. In addition to complication rates and radiographic outcomes,
      validated functional outcome tools and cost analysis of this method should be
      compared with open reduction with internal fixation. 

PMID- 24684914
TI  - Surgical management of isolated greater tuberosity fractures of the proximal
      humerus.
AB  - Because the greater tuberosity is the insertion site of the posterior superior
      rotator cuff, fractures can have a substantial impact on functional outcome.
      Isolated fractures should not inadvertently be trivialized. Thorough patient
      evaluation is required to make an appropriate treatment decision. In most cases
      surgical management is considered when there is displacement of 5 mm or greater.
      Although reduction of displaced greater tuberosity fractures has traditionally
      been performed with open techniques, arthroscopic techniques are now available.
      The most reliable techniques of fixation of the greater tuberosity incorporate
      the rotator cuff tendon bone junction rather than direct bone-to-bone fixation.

PMID- 24684915
TI  - The role of acromioplasty for rotator cuff problems.
AB  - Acromioplasty is a well-described technique used throughout the wide spectrum of
      treatment options for shoulder impingement and rotator cuff pathology. Several
      randomized prospective studies have described clinical outcomes that are
      statistically similar when comparing patients undergoing rotator cuff repair
      either with or without concomitant acromioplasty. This article reviews the
      current evidence for use of acromioplasty in patients with subacromial
      impingement syndrome and during arthroscopic rotator cuff repair. Despite
      recently published studies, more long-term data, especially with regard to
      failure rates and return-to-surgery rates over time, are needed to better
      determine the role of acromioplasty. 

PMID- 24684916
TI  - Evaluation and management of brachial plexus birth palsy.
AB  - Brachial plexus birth palsy can result in permanent lifelong deficits and
      unfortunately continues to be relatively common despite advancements in obstetric
      care. The diagnosis can be made shortly after birth by physical examination,
      noting a lack of movement in the affected upper extremity. Treatment begins with
      passive range-of-motion exercises to maintain flexibility and tactile stimulation
      to provide sensory reeducation. Primary surgery consists of microsurgical nerve
      surgery, whereas secondary surgery consists of alternative microsurgical
      procedures, tendon transfers, or osteotomies, all of which improve outcomes in
      the short term. However, the long-term outcomes of current treatment
      recommendations remain unknown. 

PMID- 24684917
TI  - Evaluation and medical management of fragility fractures of the upper extremity.
AB  - Osteoporosis continues to be a major health condition plaguing the aging
      population. The major manifestation of osteoporosis, the development of fragility
      fractures, is a burden both clinically and economically on patients and the
      nation's health care system, with up to half of all American women sustaining a
      fragility fracture in their older years. The high frequency of injuries to the
      distal radius and proximal humerus should lead upper extremity surgeons to take
      pause and recognize the magnitude of impact these fractures have on their patient
      population. Recommended interventions span a spectrum of aggressiveness and have
      various financial implications. 

PMID- 24684918
TI  - Non-neoplastic soft tissue masses that mimic sarcoma.
AB  - Non-neoplastic soft tissue masses may mimic soft tissue sarcoma in a wide variety
      of clinical settings. Systematic and thorough review of patient history, physical
      examination, imaging, laboratory results, and biopsy will allow the clinician to
      differentiate between the two in most cases. We describe several common non
      neoplastic entities that may mimic soft tissue sarcoma in case presentation
      format along with the characteristics that help distinguish them. 

PMID- 24684919
TI  - The principles and applications of fresh frozen allografts to bone and joint
      reconstruction.
AB  - Fresh frozen allograft reconstruction has been used for a long time in massive
      bone loss in orthopedic surgery. Allografts have the advantage of being biologic
      reconstructions, which gives them durability. Despite a greater number of
      complications in the short term, after 5 years these stabilize with high rates of
      survival after 10 years. The rate of early complications and the need for careful
      management in the first years has led the orthopedic surgeon to the use of other
      options. However, the potential durability of this reconstruction makes this one
      of the best options for younger patients with high life expectancy. 

PMID- 24684920
TI  - Adult reconstruction.

PMID- 24684921
TI  - Oncology.

PMID- 24684922
TI  - Trauma.

PMID- 24684923
TI  - Upper extremity.

PMID- 24684924
TI  - Field comparison of circulating antibody assays versus circulating antigen assays
      for the detection of schistosomiasis japonica in endemic areas of China.
AB  - BACKGROUND: Schistosomiasis remains a serious public health problem in affected
      countries, and routine, highly sensitive and cost-effective diagnostic methods
      are lacking. We evaluated two immunodiagnostic techniques for the detection of
      Schistosoma japonicum infections: circulating antibody and circulating antigen
      assays. METHODS: A total of 1864 individuals (between 6 and 72 years old)
      residing in five administrative villages in Hubei province were screened by serum
      examination with an indirect hemagglutination assay (IHA). The positive
      individuals (titer >=20 in IHA) were reconfirmed by stool examination with the
      Kato-Katz method (three slides from a single stool specimen). Samples of good
      serum quality and a volume above 0.5 ml were selected for further testing with
      two immunodiagnostic antibody (DDIA and ELISA) and two antigen (ELISA) assays.
      RESULTS: The average antibody positive rate in the five villages was 12.7%, while
      the average parasitological prevalence was 1.50%; 25 of the 28 egg-positive
      samples were also circulating antigen-positive. Significant differences were
      observed between the prevalence according to the Kato-Katz method and all three
      immunodiagnostic antibody assays (P-value <0.0001). Similar differences were
      observed between the Kato-Katz method and the two immunodiagnostic antigen assays
      (P-value <0.0001) and between the antigen and antibody assays (P-value <0.0001).
      CONCLUSION: Both circulating antibody and circulating antigen assays had
      acceptable performance characteristics. Immunodiagnostic techniques to detect
      circulating antigens have potential to be deployed for schistosomiasis japonica
      screening in the endemic areas.

PMID- 24684925
TI  - Evaluation of a multiplex ligation-dependent probe amplification assay for the
      detection of respiratory pathogens in oncological patients.
AB  - BACKGROUND: Respiratory tract infections are widespread and may cause significant
      morbidity and mortality in immunosuppressed populations such as oncological
      patients. OBJECTIVES: The RealAccurate Respiratory RT PCR Kit covering 14
      respiratory viruses was compared to the RespiFinder Smart22, a broad-spectrum
      multiplex ligation-dependent probe amplification (MLPA) test, targeting 22 viral
      and bacterial respiratory pathogens. STUDY DESIGN: After verification of its
      analytical performance, the clinical performance of the RespiFinder Smart22 was
      evaluated by re-analysis of 96 respiratory samples from oncological patients.
      Additionally, the time to result (TTR) of both methods was compared. RESULTS: The
      analytical performance of the RespiFinder Smart22 fulfilled all previously
      specified criteria. Concordant results in both assays were achieved in 74.0% of
      all clinical specimens and in 91.2% when only positive results were taken into
      account. The RespiFinder Smart22 yielded additional results in a total of 22
      (22.9% of 96) samples due to higher test sensitivity and a broader, highly
      multiplexed spectrum of pathogens. The TTR of a typical routine test consisting
      of three samples were 206 and 356 min for the RealAccurate Respiratory RT PCR Kit
      and the RespiFinder Smart22, respectively. However, hands-on time was reduced by
      59.0% applying the MLPA method. CONCLUSIONS: In our hands, the RespiFinder
      Smart22 showed excellent analytical performance while hands-on time was halved in
      comparison to the RT PCR method. Regarding the clinical evaluation, the MLPA
      method provided additional results in 22.9% (22/96) of specimens due to its
      comprehensive format, higher test sensitivity and the capability to detect 22
      pathogens compared to 14 with the RealAccurate Respiratory RT PCR Kit.

PMID- 24684926
TI  - Microbiota biodiversity in inflammatory bowel disease.
AB  - Gut microbiota plays a significant role in human health and energy balance, and
      provides protection against disease states. An altered balance between microbiota
      and its host (dysbiosis) would appear to contribute to the development of
      Inflammatory Bowel Disease (IBD), Crohn's Disease (CD) and Ulcerative Colitis
      (UC). CD and UC are chronic inflammatory diseases of the gastrointestinal tes. 

PMID- 24684927
TI  - The safety and acceptability of delivering an online intervention to secondary
      students at risk of suicide: findings from a pilot study.
AB  - BACKGROUND: Suicide-related behaviour is a major problem among adolescents. Yet
      relatively few studies have tested the efficacy, acceptability and safety of
      interventions for this population. We developed and pilot tested an online
      intervention for at-risk school students, which has led to reduced suicidal
      ideation, hopelessness and depressive symptoms. The aims of this study were to
      examine the safety and acceptability of the programme, and to determine which
      components were found to be most helpful and enjoyable. METHODS: This pilot study
      employed a pre-test/post-test design, with an 8-week intervention phase.
      Participants were assessed immediately before, and immediately after the
      intervention. Participants were also asked to complete a weekly questionnaire
      immediately after the intervention, and again 2 days later assessing suicidal
      ideation and distress. RESULTS: Twenty-one young people completed the
      intervention. Overall, the intervention did not lead to increases in suicidal
      ideation or distress. Participants reported enjoying the programme, in particular
      watching the video diaries and completing the activities, and said they would
      recommend the programme to a friend. Overall, the cognitive components of the
      programme were found to be most helpful. CONCLUSIONS: Overall, the programme
      appeared to be a safe and acceptable intervention for at-risk adolescents. This
      was a small, pilot study so we need to interpret the results with caution.
      However, the findings are promising and suggest that young people at risk of
      suicide can safely be included in trials as long as adequate safety procedures
      are in place. The programme is now being tested in a randomized controlled trial.

PMID- 24684928
TI  - Cue-responding during simulated routine nursing care: a mixed method study.
AB  - BACKGROUND: Failure of nurses to recognize, acknowledge, and/or explore patient
      cues/concerns may result in patients' unrecognized psychosocial and information
      needs that could have untoward consequences. With the continuous evidence of the
      need for nurses to improve their communication, a greater emphasis is needed in
      the undergraduate nursing curriculum on training students in such skills.
      OBJECTIVE: This study is to explore the cue-responding behaviors of nursing
      students during their routine care of patients in a simulated setting. DESIGN: A
      mixed methods approach. PARTICIPANTS: Senior year students. METHOD: Data was
      collected by video-taping the students' cue-responding behavior performance,
      through individual debriefing interviews, and from the student-patient actors'
      written comments and the focus group. RESULTS: Of the 110 cues in the
      conversation, 47% were acknowledged, only 12% were explored, and 53% were
      responded to with distancing behavior. Students' cue-responding behavior was a
      negative 21.8% with more cues being responded to through distancing behaviors
      than were acknowledged. Their pattern of communication was characterized by a
      focus on task completion, the use of predominately close-ended questions, and the
      giving of explanations and information based on unchecked assumptions.
      CONCLUSIONS: Learning from their individual video-taped performance and
      debriefing with facilitators helped the students to not only develop a deeper
      level of self-awareness and reflection but also caused them to think more about
      time, the culture of nursing, and the tension between task-focused and patient
      centered care. They came to value cue-responding in communication as one way of
      learning about communicating with patients. Focusing on cue-responding in
      communication also provided us with insights on the students' understanding of
      communication and the need for educators to re-emphasize person-centered
      communication and to deal with issues that go beyond technical skills. Future
      research is critical to examine its transferability to practice with continuous
      coaching and role modeling for students in clinical settings.

PMID- 24684929
TI  - Multiple sclerosis and pregnancy.
AB  - The question of pregnancy in patients with multiple sclerosis is regularly raised
      due to the prevalence of the disease in middle age women. The multiple sclerosis
      think tank (Groupe de Reflexion sur la Sclerose en Plaques [GRESEP]) decided to
      develop recommendations on this issue, with consideration to both the impact of
      multiple sclerosis on pregnancy, and that of pregnancy on the disease. As with
      topics of previous works, the formal expert consensus method was used. The
      working group was composed of hospital-based and private practice neurologists.
      The reading group was composed of neurologists, anaesthetists and obstetricians.
      Each recommendation is presented with the relevant level of consensus. 

PMID- 24684930
TI  - The DEAD box helicase RDE-12 promotes amplification of RNAi in cytoplasmic foci
      in C. elegans.
AB  - RNAi is a potent mechanism for downregulating gene expression. Conserved RNAi
      pathway components are found in animals, plants, fungi, and other eukaryotes. In
      C. elegans, the RNAi response is greatly amplified by the synthesis of abundant
      secondary small interfering RNAs (siRNAs). Exogenous double-stranded RNA is
      processed by Dicer and RDE-1/Argonaute into primary siRNA that guides target mRNA
      recognition. The RDE-10/RDE-11 complex and the RNA-dependent RNA polymerase RRF-1
      then engage the target mRNA for secondary siRNA synthesis. However, the molecular
      link between primary siRNA production and secondary siRNA synthesis remains
      largely unknown. Furthermore, it is unclear whether the subcellular sites for
      target mRNA recognition and degradation coincide with sites where siRNA synthesis
      and amplification occur. In the C. elegans germline, cytoplasmic P granules at
      the nuclear pores and perinuclear Mutator foci contribute to target mRNA
      surveillance and siRNA amplification, respectively. We report that RDE-12, a
      conserved phenylalanine-glycine (FG) domain-containing DEAD box helicase,
      localizes in P granules and cytoplasmic foci that are enriched in RSD-6 but are
      excluded from the Mutator foci. Our results suggest that RDE-12 promotes
      secondary siRNA synthesis by orchestrating the recruitment of RDE-10 and RRF-1 to
      primary siRNA-targeted mRNA in distinct cytoplasmic compartments.

PMID- 24684931
TI  - The Vasa Homolog RDE-12 engages target mRNA and multiple argonaute proteins to
      promote RNAi in C. elegans.
AB  - Argonaute (AGO) proteins are key nuclease effectors of RNAi. Although purified
      AGOs can mediate a single round of target RNA cleavage in vitro, accessory
      factors are required for small interfering RNA (siRNA) loading and to achieve
      multiple-target turnover. To identify AGO cofactors, we immunoprecipitated the C.
      elegans AGO WAGO-1, which engages amplified small RNAs during RNAi. These studies
      identified a robust association between WAGO-1 and a conserved Vasa ATPase
      related protein RDE-12. rde-12 mutants are deficient in RNAi, including viral
      suppression, and fail to produce amplified secondary siRNAs and certain
      endogenous siRNAs (endo-siRNAs). RDE-12 colocalizes with WAGO-1 in germline P
      granules and in cytoplasmic and perinuclear foci in somatic cells. These findings
      and our genetic studies suggest that RDE-12 is first recruited to target mRNA by
      upstream AGOs (RDE-1 and ERGO-1), where it promotes small RNA amplification
      and/or WAGO-1 loading. Downstream of these events, RDE-12 forms an RNase
      resistant (target mRNA-independent) complex with WAGO-1 and may thus have
      additional functions in target mRNA surveillance and silencing.

PMID- 24684932
TI  - MUT-14 and SMUT-1 DEAD box RNA helicases have overlapping roles in germline RNAi
      and endogenous siRNA formation.
AB  - More than 2,000 C. elegans genes are targeted for RNA silencing by the mutator
      complex, a specialized small interfering RNA (siRNA) amplification module which
      is nucleated by the Q/N-rich protein MUT-16. The mutator complex localizes to
      Mutator foci adjacent to P granules at the nuclear periphery in germ cells. Here,
      we show that the DEAD box RNA helicase smut-1 functions redundantly in the
      mutator pathway with its paralog mut-14 during RNAi. Mutations in both smut-1 and
      mut-14 also cause widespread loss of endogenous siRNAs. The targets of mut-14 and
      smut-1 largely overlap with the targets of other mutator class genes; however,
      the mut-14 smut-1 double mutant and the mut-16 mutant display the most dramatic
      depletion of siRNAs, suggesting that they act at a similarly early step in siRNA
      formation. mut-14 and smut-1 are predominantly expressed in the germline and,
      unlike other mutator class genes, are specifically required for RNAi targeting
      germline genes. A catalytically inactive, dominant-negative missense mutant of
      MUT-14 is RNAi defective in vivo; however, mutator complexes containing the
      mutant protein retain the ability to synthesize siRNAs in vitro. The results
      point to a role for mut-14 and smut-1 in initiating siRNA amplification in germ
      cell Mutator foci, possibly through the recruitment or retention of target mRNAs.

PMID- 24684933
TI  - Entrainment of prefrontal beta oscillations induces an endogenous echo and
      impairs memory formation.
AB  - Brain oscillations across all frequency bands play a key role for memory
      formation. Specifically, desynchronization of local neuronal assemblies in the
      left inferior prefrontal cortex (PFC) in the beta frequency (~18 Hz) has been
      shown to be central for encoding of verbal memories. However, it remains elusive
      whether prefrontal beta desynchronization is causally relevant for memory
      formation and whether these endogenous beta oscillations can be entrained by
      external stimulation. By using combined EEG-TMS (transcranial magnetic
      stimulation), we here address these fundamental questions in human participants
      performing a word-list learning task. Confirming our predictions, memory encoding
      was selectively impaired when the left inferior frontal gyrus (IFG) was driven at
      beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz)
      and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained
      oscillatory "echo" in the left IFG, which outlasted the stimulation period by
      approximately 1.5 s, was observed solely after beta stimulation. The strength of
      this beta echo was related to memory impairment on a between-subjects level.
      These results show endogenous oscillatory entrainment effects and behavioral
      impairment selectively in beta frequency for stimulation of the left IFG,
      demonstrating an intimate causal relationship between prefrontal beta
      desynchronization and memory formation.

PMID- 24684934
TI  - Receipt of seminal fluid proteins causes reduction of male investment in a
      simultaneous hermaphrodite.
AB  - Mating partners often have conflicting interests when copulating. One of the
      major agents affecting female mating partners is seminal fluid, transferred along
      with sperm. The role of seminal fluid proteins (SFPs) in reproductive success is
      well studied in separate-sexed animals but is much less so in simultaneous
      hermaphrodites. The latter potentially have a unique target to exploit for the
      sperm donor's own benefit: the male function of their mating partners. Here we
      show that, in the great pond snail Lymnaea stagnalis, receipt of specific SFPs
      reduces both sperm transfer and paternity success in a subsequent insemination
      event. Lowering investment in the mating partner's male function constitutes a
      novel role for SFPs. This demonstrates for the first time that hermaphrodites
      alter their mates' male as well as female reproductive output. Although it
      remains to be tested whether this represents mate manipulation or an adaptive
      response of recipients, our findings identify male investment as a new target for
      postcopulatory sexual selection.

PMID- 24684936
TI  - Social calls predict foraging success in big brown bats.
AB  - Animals foraging in the dark are engaged simultaneously in prey pursuit,
      collision avoidance, and interactions with conspecifics, making efficient
      nonvisual communication essential. A variety of birds and mammals emit food
      associated calls that inform, attract, or repel conspecifics (e.g.,). Big brown
      bats (Eptesicus fuscus) are insectivorous aerial hawkers that may forage near
      conspecifics and are known to emit social calls (e.g.,). Calls recorded in a
      foraging setting might attract (e.g.,) or repel conspecifics and could denote
      territoriality or food claiming. Here, we provide evidence that the "frequency
      modulated bout" (FMB), a social call emitted only by male bats (exclusively in a
      foraging context), is used to claim food and is individually distinct. Bats were
      studied individually and in pairs in a flight room equipped with synchronized
      high-speed stereo video and audio recording equipment while sex and experience
      with a foraging task were experimentally manipulated. Male bats emitting the FMB
      showed greater success in capturing prey. Following FMB emission, interbat
      distance, diverging flight, and the other bat's distance to the prey each
      increased. These findings highlight the importance and utility of vocal
      communication for a nocturnal animal mediating interactions with conspecifics in
      a fast-paced foraging setting.

PMID- 24684935
TI  - Nutritional state modulates the neural processing of visual motion.
AB  - Food deprivation alters the processing of sensory information, increasing neural
      activity in the olfactory and gustatory systems in animals across phyla. Neural
      signaling is metabolically costly, and a hungry animal has limited energy
      reserves, so we hypothesized that neural activity in other systems may be
      downregulated by food deprivation. We investigated this hypothesis in the motion
      vision pathway of the blowfly. Like other animals, flies augment their motion
      vision when moving: they increase the resting activity and gain of visual
      interneurons supporting the control of locomotion and gaze. In the present study,
      walking-induced changes in visual processing depended on the nutritional state
      they decreased with food deprivation and recovered after subsequent feeding. We
      found that changes in the motion vision pathway depended on walking speed in a
      manner dependent on the nutritional state. Walking also reduced response
      latencies in visual interneurons, an effect not altered by food deprivation.
      Finally, the optomotor reflex that compensates for visual wide-field motion was
      reduced in food-deprived flies. Thus, walking augmented motion vision, but the
      effect was decreased when energy reserves were low. Our results suggest that
      energy limitations may drive the rebalancing of neural activity with changes in
      the nutritional state.

PMID- 24684937
TI  - Dopaminergic modulation of cAMP drives nonlinear plasticity across the Drosophila
      mushroom body lobes.
AB  - BACKGROUND: Activity of dopaminergic neurons is necessary and sufficient to evoke
      learning-related plasticity in neuronal networks that modulate learning. During
      olfactory classical conditioning, large subsets of dopaminergic neurons are
      activated, releasing dopamine across broad sets of postsynaptic neurons. It is
      unclear how such diffuse dopamine release generates the highly localized patterns
      of plasticity required for memory formation. RESULTS: Here we have mapped spatial
      patterns of dopaminergic modulation of intracellular signaling and plasticity in
      Drosophila mushroom body (MB) neurons, combining presynaptic thermogenetic
      stimulation of dopaminergic neurons with postsynaptic functional imaging in vivo.
      Stimulation of dopaminergic neurons generated increases in cyclic AMP (cAMP)
      across multiple spatial regions in the MB. However, odor presentation paired with
      stimulation of dopaminergic neurons evoked plasticity in Ca(2+) responses in
      discrete spatial patterns. These patterns of plasticity correlated with
      behavioral requirements for each set of MB neurons in aversive and appetitive
      conditioning. Finally, broad elevation of cAMP differentially facilitated
      responses in the gamma lobe, suggesting that it is more sensitive to elevations
      of cAMP and that it is recruited first into dopamine-dependent memory traces.
      CONCLUSIONS: These data suggest that the spatial pattern of learning-related
      plasticity is dependent on the postsynaptic neurons' sensitivity to cAMP
      signaling. This may represent a mechanism through which single-cycle conditioning
      allocates short-term memory to a specific subset of eligible neurons (gamma
      neurons).

PMID- 24684938
TI  - A comparison of patient-reported and measured range of motion in a cohort of
      total knee arthroplasty patients.
AB  - Range of motion (ROM) is an important component of the assessment of total knee
      arthroplasty (TKA) outcome. We compared patient-reported versus clinically
      observed ROM in a prospective cohort. Clinically observed ROM was measured using
      a goniometer by a trained research assistant. Self-reported ROM was estimated
      using a set of lateral knee photographs depicting varying levels of flexion and
      extension. All measures were taken pre-operatively, three, and six months
      postoperatively. We found statistically significant associations between self
      reported ROM and clinically observed ROM for flexion and extension (all P <
      0.001). We dichotomized flexion at 90 degrees  and found that self-report had a
      specificity of 94% and sensitivity of 65%. We conclude that patient-reported ROM
      may be a useful outcome measure for TKA.

PMID- 24684939
TI  - Age-based prediction of incidence of complications during inpatient stroke
      rehabilitation: a retrospective longitudinal cohort study.
AB  - BACKGROUND: Stroke complications can occur not only in the acute ward but also
      during the subsequent rehabilitation period. However, existing studies have not
      adequately addressed the incidence of various complications among stroke in
      patients undergoing rehabilitation using a longitudinal method. We aimed to
      investigate the longitudinal impact of age on complication rates in patients
      undergoing inpatient stroke rehabilitation at different disease stages. METHODS:
      Five hundred and sixty-eight first-time stroke patients transferred to the
      rehabilitation ward between July 2002 and June 2012 were included in the study.
      Patients were stratified into age groups for comparison: <65 years (young), 65
      years to <75 years (younger old), and >=75 years (older old). In total, 30
      different complication types were recorded for analysis. RESULTS: Constipation,
      shoulder pain, symptomatic urinary tract infection (UTI), and fever were common
      complications during initial stay in the rehabilitation ward, and incidence was
      >10% in all three age groups. The frequency of incidence of upper
      gastrointestinal bleeding (UGIB) was higher in the younger old (17.9%) and older
      old (20.6%) groups than in the young group (4.1%) during initial stay in the
      rehabilitation ward (p < 0.001). The incidence of UGIB was higher in the younger
      old (8.04%) and older old (8.33%) groups than in the young group (0.19%) during
      subsequent stay in the rehabilitation ward (p = 0.011). The incidence of
      symptomatic UTI was higher in the younger old (21.0%) and older old (20.0%)
      groups than in the young group (11.5%) during initial stay in the rehabilitation
      ward (p = 0.019). The incidence of symptomatic UTI was higher in the older old
      group (29.17%) than in the younger old (9.21%) and young (3.14%) groups during
      subsequent stay in the rehabilitation ward (p < 0.001). CONCLUSIONS: Age does not
      affect every complication type. UGIB and symptomatic UTI occurred more frequently
      in stroke patients aged >=65 years during their stay in the rehabilitation ward.

PMID- 24684940
TI  - The Stroke Oxygen Study (SO2S) - a multi-center, study to assess whether routine
      oxygen treatment in the first 72 hours after a stroke improves long-term outcome:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Mild hypoxia is common in stroke patients and may have significant
      adverse effects on the ischemic brain after stroke. The use of oxygen treatment
      is rapidly increasing in European stroke units but is not without side effects.
      It impedes early mobilization, could pose an infection risk, and may encourage
      the formation of toxic free radicals, leading to further damage to the ischemic
      brain. In the Stroke Oxygen Pilot Study (2 or 3 L/min for 72 hours) neurological
      recovery at one week was better in the oxygen group than in controls, and after
      correction for difference in baseline stroke severity and prognostic factors,
      there was a trend to better outcome with oxygen at six months. Oxygen was as
      effective in mild as in severe strokes.Oxygen saturation is lower at night than
      during the day, and episodes of oxygen desaturation are common during sleep.
      Nocturnal oxygen supplementation is likely to reduce the burden of hypoxia
      without interfering with daytime mobilization and rehabilitation.Before wider use
      of oxygen supplementation becomes established it is important to obtain better
      evidence on which patients benefit from such treatment. METHODS: Participants
      will be randomized to one of three groups: the first will receive continuous
      oxygen for 72 hours (at a rate of 2 or 3 L/min depending on baseline oxygen
      saturation), the second group will receive nocturnal oxygen only (at a rate of 2
      or 3 L/min depending on baseline oxygen saturation) and the third group will not
      receive any oxygen (control). A baseline assessment is performed at randomization
      and a one-week follow-up completed. Outcome data at three, six and twelve months
      will be obtained via a questionnaire sent to the patient by the trial center.
      DISCUSSION: This study will provide evidence on the effectiveness of oxygen
      supplementation for the treatment of stroke and whether nocturnal oxygen is a
      potentially beneficial therapy regimen. TRIAL REGISTRATION: This trial is
      registered with the ISRCTN register ID number ISRCTN52416964.

PMID- 24684942
TI  - The Richmond Agitation-Sedation Scale modified for palliative care inpatients
      (RASS-PAL): a pilot study exploring validity and feasibility in clinical
      practice.
AB  - BACKGROUND: The Richmond Agitation-Sedation Scale (RASS), which assesses level of
      sedation and agitation, is a simple observational instrument which was developed
      and validated for the intensive care setting. Although used and recommended in
      palliative care settings, further validation is required in this patient
      population. The aim of this study was to explore the validity and feasibility of
      a version of the RASS modified for palliative care populations (RASS-PAL).
      METHODS: A prospective study, using a mixed methods approach, was conducted.
      Thirteen health care professionals (physicians and nurses) working in an acute
      palliative care unit assessed ten consecutive patients with an agitated delirium
      or receiving palliative sedation. Patients were assessed at five designated time
      points using the RASS-PAL. Health care professionals completed a short survey and
      data from semi-structured interviews was analyzed using thematic analysis.
      RESULTS: The inter-rater intraclass correlation coefficient range of the RASS-PAL
      was 0.84 to 0.98 for the five time points. Professionals agreed that the tool was
      useful for assessing sedation and was easy to use. Its role in monitoring
      delirium however was deemed problematic. Professionals felt that it may assist
      interprofessional communication. The need for formal education on why and how to
      use the instrument was highlighted. CONCLUSION: This study provides preliminary
      validity evidence for the use of the RASS-PAL by physicians and nurses working in
      a palliative care unit, specifically for assessing sedation and agitation levels
      in the management of palliative sedation. Further validity evidence should be
      sought, particularly in the context of assessing delirium.

PMID- 24684941
TI  - A hemangioma of the sigmoid colon mesentery presenting as a retroperitonealtumor:
      a case report and review.
AB  - Hemangiomas of the gastrointestinal tract and mesentery are uncommon benign
      vascular lesions. While spontaneous bleeding is the hallmark of the
      gastrointestinal tumor variant, clinical signs of mesenteric hemangiomas are
      mostly unspecific. Despite the increasing imaging quality of computerized
      tomography (CT), in most cases the final diagnosis is established through surgery
      and histopathologic analysis of a macrobiopsy.We present a case report of a 20
      year-old female patient who was admitted with progressive abdominal distension
      and suffered from persistent abdominal pain for 3 months. A large retroperitoneal
      tumor mass was detected on the CT scan. Due to radiographic signs of an
      intraabdominal liposarcoma, an explorative laparotomy was performed revealing a
      large hemangioma originating from the mesosigmoid.Although rare, gastrointestinal
      hemangiomas should be kept in mind by oncological visceral surgeons as one
      differential diagnosis of large intraabdominal tumorous masses, especially in
      young adults.

PMID- 24684944
TI  - A reduction of sleep spindles heralds seizures in focal epilepsy.
AB  - OBJECTIVES: Sleep has profound effects on epilepsy. It may alter the occurrence
      of interictal discharges (IEDs) and seizures. Vice versa, an active epilepsy
      changes sleep. Sleep spindles are typically associated with an increase of IEDs.
      We examined whether seizures change the number and power of spindles preceding
      nightly seizures. METHODS: We retrospectively examined the nightly EEG recordings
      of presurgical epilepsy patients from our EEG-video-monitoring unit. We evaluated
      the 200s before the EEG seizure onset for spindle density (spindles per minute)
      and spindle power and compared that to the interictal baseline sleep. RESULTS:
      The spindle density and the spindle power decreased significantly before the
      first seizure. The reduction before secondarily generalized seizures (8.7+/-2.5;
      p=0.001) was more pronounced than before focal seizures (10.5+/-2.5; p=0.003)
      compared to baseline (12.2+/-2.7). This finding was more pronounced in
      extratemporal lobe epilepsies than in temporal lobe epilepsies. The reduction of
      spindle power was also significant and was more pronounced in XTLE. These results
      were consistent for all other seizures during sleep, the mean spindle density
      decreased significantly in all focal (10.2+/-1.9; p=0.001) and generalized
      preictal period (8.8+/-2.4; p=0.001) compared to the mean interictal period
      (12.1+/-2.1). These were also more significant in XTLE than TLE group.
      CONCLUSIONS: Our data demonstrate that the occurrence of seizures and propensity
      of seizure generalisation in focal epilepsy is modulated by specific
      characteristics of light sleep such as sleep spindles. SIGNIFICANCE: This study
      supports the notion that changes in the epileptic network precede the seizure
      onset and have an influence on seizure generation and termination.

PMID- 24684943
TI  - Host-biting rate and susceptibility of some suspected vectors to Leishmania
      braziliensis.
AB  - BACKGROUND: American tegumentary leishmaniasis is a serious Brazilian public
      health problem. This diseases is attributed to seven species of Leishmania,
      however, the majority of cases are associated with Leishmania braziliensis. Some
      phlebotomine species have been implicated in the transmission of this parasite,
      nonetheless only Psychodopygus wellcomei has had its vectorial competence
      demonstrated. Thus this study sought to assess some parameters related to the
      vectorial capacity of anthropophilic species of sand fly occurring in Sao Paulo
      state: Pintomyia fischeri, Migonemyia migonei Nyssomyia intermedia, Nyssomyia
      whitmani, Expapillata firmatoi and Psychodopygus ayrozai, under laboratory
      conditions. These parameters were the duration of the gonotrophic cycle,
      proportion of females which feed on hamster, the rate of infection by L.
      braziliensis and the duration of the extrinsic incubation period. METHODS: The
      sandflies were collected in three regions of the Sao Paulo state: Greater Sao
      Paulo and the Mogi Guacu and Iporanga municipalities. To assess the proportion of
      engorged females the insects were fed on hamsters to estimate the duration of the
      gonotrophic cycle. To estimate the susceptibility to infection of each species,
      their females were fed on hamsters infected with Leishmania braziliensis and
      dissected to ascertain the localization of the flagellates and estimate the
      extrinsic incubation period. RESULTS: Low hamster attractiveness to Ps. ayrozai
      was observed. A high proportion of engorged females was observed when the hamster
      had its whole body exposed. The gonotrophic cycle ranged between three and eight
      days. Mg. migonei, Pi. fischeri, Ny. neivai, Ny. intermedia, Ny. whitmani and
      Ex.firmatoi presented susceptibility to infection by L. braziliensis. The highest
      infection rate (34.4%) was observed for Ny. whitmani and the lowest for Ny.
      intermedia (6.6%). Mg. migonei presented late-stage infection forms on the fifth
      day after feeding, but in the other species these forms were observed as from the
      fourth day. CONCLUSIONS: Our results, together with other parameters of their
      behavior under natural conditions, suggest the potential role of Ex. firmatoi as
      vector of this parasite and reinforce that of Mg. migonei, Pi. fischeri, Ny.
      neivai, Ny. intermedia and Ny. whitmani in the areas in which they occur.

PMID- 24684945
TI  - Editors' Pick: milk sugar, migration and pastoralism in Africa.

PMID- 24684946
TI  - Can an Internet-based intervention reduce suicidal ideation, depression and
      hopelessness among secondary school students: results from a pilot study.
AB  - AIM: Little evidence exists regarding the efficacy of suicide prevention
      programmes among the youth. This pilot study aimed to test the effects of a
      specifically designed, eight-module Internet-based programme on suicidal ideation
      among secondary school students. METHODS: The study employed a pre-test/post-test
      design. Outcomes of interest were suicidal ideation, depression and hopelessness.
      Participants were recruited via the school well-being team, were assessed at
      baseline and immediately post-intervention. The intervention was delivered weekly
      at the young persons' school. RESULTS: Twenty-one students completed all eight
      modules and a post-intervention assessment, and constitute the observed case
      sample used for the analysis. Overall levels of suicidal ideation, depressive
      symptoms and hopelessness decreased significantly over the course of the study.
      CONCLUSIONS: This was a small pilot study with no control group. However,
      significant reductions were seen in suicidal ideation, depressive symptoms and
      hopelessness, indicating that Internet-based interventions may hold promise when
      it comes to reducing suicide risk among youth. Further investigation is
      warranted.

PMID- 24684947
TI  - Footwear traction and three-dimensional kinematics of level, downhill, uphill and
      cross-slope walking.
AB  - Outdoor activities are a popular form of recreation, with hiking being the most
      popular outdoor activity as well as being the most prevalent in terms of injury.
      Over the duration of a hike, trekkers will encounter many different sloped
      terrains. Not much is known about the required traction or foot-floor kinematics
      during locomotion on these sloped surfaces, therefore, the purpose was to
      determine the three-dimensional foot-floor kinematics and required traction
      during level, downhill, uphill and cross-slope walking. Ten participants
      performed level, uphill, downhill and cross-slope walking along a 19 degrees 
      inclined walkway. Ground reaction force data as well as 3D positions of retro
      reflective markers attached to the shoe were recorded using a Motion Analysis
      System. Peak traction coefficients and foot-floor kinematics during sloped
      walking were compared to level walking. When walking along different sloped
      surfaces, the required traction coefficients at touchdown were not different from
      level walking, therefore, the increased likelihood of heel slipping during hiking
      is potentially due to the presence of loose material (rocks, dirt) on hiking
      slopes, rather than the overall lack of traction. Differences in required
      traction were seen at takeoff, with uphill and cross-sloped walking requiring a
      greater amount of traction compared to level walking. Changes in sagittal plane,
      frontal plane and transverse plane foot-floor angles were seen while walking on
      the sloped surfaces. Rapid foot-floor eversion was observed during cross-slope
      walking which could place the hiker at risk of injury with a misstep or if there
      was a slight slip. 

PMID- 24684949
TI  - Commentary on: the economic cost of firearm-related injuries in the United States
      from 2006 to 2010.

PMID- 24684948
TI  - Physical activity program for patients with dementia and their relative
      caregivers: randomized clinical trial in Primary Health Care (AFISDEMyF study).
AB  - BACKGROUND: The aging of the population has led to the increase of chronic
      diseases, especially dementia and cardiovascular diseases, and it has become
      necessary for their relatives to dedicate more time in caregiving.The objective
      in the first phase of this study is to evaluate the effectiveness of a Primary
      Health Care procedure to increase the physical activity of people with dementia
      and their relative caregivers. Also the effect on the cognitive state and
      cardiovascular risk will be assessed. METHODS/DESIGN:  DESIGN: Clinical,
      multicentric and randomized trial. A simple random sampling to select 134
      patients diagnosed with dementia will be carried out. After contacting their
      relatives, his/her participation in the trial will be requested. A basal
      assessment will be made and the participants will be asigned to control or
      intervention group (1:1). VARIABLES: The main measure will be the assessment of
      physical activity (podometer and 7-PAR) in patients and caregivers. In patients
      with dementia: ADAS-cog, functional degree and cardiovascular risk. In
      caregivers: cardiovascular risk, general health and quality of life.
      INTERVENTION: For 3 months, participants will receive instructions to do physical
      activity with an adapted program. This program will be designed and applied by
      Primary Health Care professionals in patients with dementia and their caregivers.
      The control group will receive regular care. ANALYSIS: An intention-to-treat
      analysis will be carried out by comparing the observed differences between basal,
      6 and 12 months measures. Change in the mean of daily steps assessed with the
      podometer and 7-PAR will be the main result. DISCUSSION: If the main hypothesis
      is confirmed, it could be useful to improve the cognitive state of patients with
      dementia, as well as the cardiovascular risk of all of them. The results can be
      good to improve technical features of the devices that register the physical
      activity in the patients with dementia, and it could facilitate its
      commercialization. TRIAL REGISTRATION: Clinical Trials.gov Identifier:
      NCT02044887.

PMID- 24684950
TI  - The economic cost of firearm-related injuries in the United States from 2006 to
      2010.
AB  - BACKGROUND: Estimates of the number of firearm-related injuries widely vary.
      Although focus has been primarily on deaths, the societal cost of caring for
      victims of these injuries is largely unknown. Our goal was to estimate the
      economic impact of nonfatal, firearm-related injuries in the United States based
      on recent, publically available data. METHODS: We queried several national
      registries for hospital and emergency department (ED) discharges from 2006 to
      2010 to estimate the annual incidence of firearm-related injuries. The cost of
      direct medical services and lost productivity from firearm-related injuries were
      extrapolated from recently published estimates. To identify potentially important
      trends, we compared the economic impact and payor mix for firearm-related
      injuries in 2006 with those in 2010. RESULTS: During the 5-year analytic period,
      we identified 385,769 (SE = 29,328) firearm-related ED visits resulting in
      141,914 (SE = 14,243) hospital admissions, costing more than $88 billion (SE =
      $8.0 billion). Between 2006 and 2010, there was a decrease in the rate of
      hospital visits from 6.65 per 10,000 visits in 2006 to 5.76 per 10,000 visits in
      2010 (P < .001). Similarly, the rate of hospital admissions and ED visits without
      admission decreased from 2.58 per 10,000 to 1.96 per 10,000 (P < .001) and 4.08
      per 10,000 to 3.79 per 10,000 (P < .001). Regression of the economic costs from
      2006 to 2010, adjusted for Consumer Price Index, showed no change (P = .15).
      There was a decrease in the proportion of Uninsured between 2006 and 2010 from
      51.6% to 46.78% (P < .001). CONCLUSION: Firearm-related injuries are a major
      economic burden to not only the American health care system but also to American
      society. The incidence of these injuries has decreased slightly from 2006 to
      2010, with no change in the economic burden. Research aimed at understanding the
      associated financial, social, health, and disability-related issues related to
      firearm injuries is necessary and would likely enhance our knowledge of the
      causes of these events, and may accelerate development of interventions and
      policies to decrease the staggering medical and societal cost of gun violence.

PMID- 24684951
TI  - Commentary on: the economic cost of firearm-related injuries in the United States
      from 2006 to 2010.

PMID- 24684952
TI  - CDH1 polymorphisms and haplotypes in sporadic diffuse and intestinal gastric
      cancer: a case-control study based on direct sequencing analysis.
AB  - BACKGROUND: Findings related to the influence of the -160C -> A promoter
      polymorphism and haplotypes of the E-cadherin (CDH1) gene have not been
      consistent in previous studies regarding the risk for sporadic gastric cancer.
      Investigators in most previous studies detected those genotypes using restriction
      fragment length polymorphism analysis. Therefore, we conducted a case-control
      study to investigate the association of the CDH1 - 160C -> A promoter
      polymorphism and haplotypes for cancer risk related to sporadic diffuse and
      intestinal gastric cancer by direct sequencing analysis. METHODS: We included 107
      diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134
      controls. The genotypic polymorphisms in the -160 promoter region, exons and
      intron-exon boundaries of CDH1 were detected by direct sequencing analysis.
      Genotype frequencies were compared. The CDH1 - 160C -> A promoter polymorphism
      and four polymorphisms (48 + 6 T -> C, 2076C -> T, 2253C -> T and 1937-13 T -> C)
      were included in the haplotype analyses, which were estimated using the
      expectation-maximization algorithm. RESULTS: Compared to controls, the frequency
      of the -160A allele was significantly higher in diffuse gastric cancer cases (P =
      0.005), but it was not significantly different in intestinal gastric cancer cases
      (P = 0.119). Two sets of three-marker haplotypes (-160C -> A, 48 + 6 T -> C,
      2076C -> T and -160C -> A, 1937-13 T -> C, 2253C -> T) were associated with the
      risk of diffuse gastric cancer (P = 0.011 and P = 0.042, respectively).
      CONCLUSION: Based on direct sequencing analysis, our findings suggest that the
      CDH1 - 160C -> A promoter polymorphism and haplotypes play significant roles in
      cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric
      cancer, in a Taiwanese population.

PMID- 24684953
TI  - Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L
      based on hollow fiber assay.
AB  - BACKGROUND: Stellera chamaejasme L, a traditional Chinese herb, has long been
      used for treatment of various tumors in the Chinese population. In our previous
      study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera
      chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from
      ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in
      vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2
      had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC
      2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor
      active fraction of ESC might exist in ESC-2. Here, we further observe the
      inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo.
      METHODS: In this study, we used hollow fiber tumor model to evaluate the
      inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic
      rates of the cancer cells retrieved from the hollow fibers were measured with
      flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by
      colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-alpha expression were determined
      with elisa assay and radioimmunoassay respectively. RESULTS: The results showed
      that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the
      effect strength, dose and antitumor spectrum, the order of antitumor effects of
      ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs.
      ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme
      activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas
      L protein, but TNF-alpha/TNFR1 protein expression in NCI-H460 cells changed
      significantly after ESC and ESC-2 treatment. CONCLUSION: ESC-2 had the similar
      antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be
      the main antitumor active fraction of ESC, which was consistent with our previous
      results in vitro.

PMID- 24684954
TI  - Hormone abnormalities are not related to the erectile dysfunction and decreased
      libido found in many men with infertility.
AB  - OBJECTIVE: To evaluate whether hormonal markers predict erectile dysfunction (ED)
      and symptoms of T deficiency syndrome (TDS), which are commonly found in the
      population of infertile men. DESIGN: Retrospective study utilizing a
      prospectively maintained infertility database. SETTING: A tertiary referral
      center. PATIENT(S): A total of 1,750 of 2,783 men presenting for evaluation of
      infertility between 1995 and 2010 completed validated questionnaires.
      INTERVENTION(S): Androgen Deficiency in the Aging Male (ADAM) and Sexual Health
      Inventory for Men questionnaires were administered. Baseline risk factors for ED
      and TDS were also measured. Subjects underwent serum hormone evaluation for total
      T, calculated bioavailable T, sex hormone-binding globulin, E2, LH, FSH, and PRL.
      MAIN OUTCOME MEASURE(S): Multivariable logistic regression modeling was used to
      determine the significance of hormonal markers in predicting ED (Sexual Health
      Inventory for Men score <22) and/or a positive ADAM score. RESULT(S): The
      prevalence of ED and a positive response to the ADAM questionnaire were 30.5% and
      45.2%, respectively, in this population (mean age, 36 years). Low serum T (total
      T < 10 nmol/L) was found in 29.4%. Neither T nor bioavailable T was significantly
      associated with the symptoms of ED or TDS on multivariable regression analysis.
      CONCLUSION(S): Erectile dysfunction and TDS in young, infertile men seem to be
      unrelated to hormone changes.

PMID- 24684955
TI  - Ovarian tissue cryopreservation: a committee opinion.
AB  - Ovarian tissue cryopreservation is an option to preserve reproductive potential
      in patients who must urgently undergo aggressive chemotherapy and/or radiotherapy
      or who have other medical conditions requiring treatment that may threaten
      ovarian function and subsequent fertility. Ovarian tissue cryopreservation may be
      the only option available to prepubertal girls undergoing such treatments.
      However, these techniques are still considered to be experimental. This document
      outlines the current technology, clinical outcomes, and risks of ovarian tissue
      cryopreservation and recommendations for clinical applications. This document and
      the document "Mature Oocyte Cryopreservation: A Guideline" published in 2013
      (Fertil Steril 2013;99:37-43) replace the document "Ovarian Tissue and Oocyte
      Cryopreservation" last published in 2008 (Fertil Steril 2008;90:S241-6). 

PMID- 24684956
TI  - Differences in ovarian hormones in relation to parity and time since last birth.
AB  - OBJECTIVE: To examine ovarian function in relation to parity and time since last
      birth. DESIGN: Cross-sectional study. SETTING: Health-care program in California.
      PATIENT(S): 346 naturally cycling women, aged 18 to 39 years. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Mean follicular urinary estradiol metabolite
      concentration (E1C) (cycle days -8 to -1), mean luteal progesterone metabolite
      concentration (PdG) (days 0 to +10), and cycle phase lengths in ovulatory cycles.
      RESULT(S): After the women had collected daily urine samples for up to eight
      menstrual cycles, we measured the E1C and PdG using enzyme-linked immunoassay.
      The cycle phase lengths were calculated from the hormone profiles and daily
      diaries. Women who had given birth within the previous 3 years had lower E1C than
      the nulliparous women and women who last given birth >3 years earlier. Among the
      parous women, E1C was positively associated with the time since last birth. Women
      who last gave birth >3 years earlier had longer follicular phases than the
      nulliparous women. There were no associations between parity and PdG or luteal
      phase length. CONCLUSION(S): Our cross-sectional data suggest that ovarian
      function differs in nulliparous and parous women and is positively associated
      with the time since last birth. Longitudinal research is needed to explore within
      woman changes in ovarian function prepartum and postpartum.

PMID- 24684958
TI  - FISH Oracle 2: a web server for integrative visualization of genomic data in
      cancer research.
AB  - BACKGROUND: A comprehensive view on all relevant genomic data is instrumental for
      understanding the complex patterns of molecular alterations typically found in
      cancer cells. One of the most effective ways to rapidly obtain an overview of
      genomic alterations in large amounts of genomic data is the integrative
      visualization of genomic events. RESULTS: We developed FISH Oracle 2, a web
      server for the interactive visualization of different kinds of downstream
      processed genomics data typically available in cancer research. A powerful search
      interface and a fast visualization engine provide a highly interactive
      visualization for such data. High quality image export enables the life scientist
      to easily communicate their results. A comprehensive data administration allows
      to keep track of the available data sets. We applied FISH Oracle 2 to published
      data and found evidence that, in colorectal cancer cells, the gene TTC28 may be
      inactivated in two different ways, a fact that has not been published before.
      CONCLUSIONS: The interactive nature of FISH Oracle 2 and the possibility to
      store, select and visualize large amounts of downstream processed data support
      life scientists in generating hypotheses. The export of high quality images
      supports explanatory data visualization, simplifying the communication of new
      biological findings. A FISH Oracle 2 demo server and the software is available at
      http://www.zbh.uni-hamburg.de/fishoracle.

PMID- 24684957
TI  - Segmented filamentous bacteria antigens presented by intestinal dendritic cells
      drive mucosal Th17 cell differentiation.
AB  - How commensal microbiota contributes to immune cell homeostasis at barrier
      surfaces is poorly understood. Lamina propria (LP) T helper 17 (Th17) cells
      participate in mucosal protection and are induced by commensal segmented
      filamentous bacteria (SFB). Here we show that MHCII-dependent antigen
      presentation of SFB antigens by intestinal dendritic cells (DCs) is crucial for
      Th17 cell induction. Expression of MHCII on CD11c(+) cells was necessary and
      sufficient for SFB-induced Th17 cell differentiation. Most SFB-induced Th17 cells
      recognized SFB in an MHCII-dependent manner. SFB primed and induced Th17 cells
      locally in the LP and Th17 cell induction occurred normally in mice lacking
      secondary lymphoid organs. The importance of other innate cells was unveiled by
      the finding that MHCII deficiency in group 3 innate lymphoid cells (ILCs)
      resulted in an increase in SFB-independent Th17 cell differentiation. Our results
      outline the complex role of DCs and ILCs in the regulation of intestinal Th17
      cell homeostasis.

PMID- 24684959
TI  - Polishing for glass ceramics: which protocol?
AB  - PURPOSE: The execution of adjustments on ceramic restorations is sometimes
      necessary for either correction of occlusion and/or inadequate contours or
      esthetical improvements. Clinically, the surfaces undergo weariness through fine
      grinding diamond burs which remove the superficial glazing layer. Several
      materials for ceramic polishing have been used in an attempt to reach a
      satisfactory surface smoothness. The aim of this study was to perform a
      literature review on different polishing protocols of several dental ceramics.
      STUDY SELECTION: This is a literature review performed through scientific
      articles published between 2004 and 2012, indexed in MEDLINE, PubMed and Scielo
      databases. The study selected and analyzed a total of 20 relevant articles that
      evaluated different types of ceramics, polishing treatment and surface roughness.
      RESULTS: After an extensive literature review, this study observed: 1 - after the
      rupture of the glazing layer due to the adjustments of the restorations, the best
      choice for the polishing of the surface will depend on the type of ceramics used;
      2 - glazing procedure provide excellent results regarding to the superficial
      smoothness; however, if reglazing is impossible, either abrasive rubber
      cups/points or sandpaper discs followed by the use of diamond polishing pastes
      results in a satisfactory superficial smoothness; 3 - clinical studies that take
      into account the behavior of the protocols polishing are scarce and should be
      encouraged; 4 - the large number of variables influence the final outcome of
      polishing should be considered. CONCLUSIONS: The necessity in standardization of
      methodologies to enable a comparison among researches.

PMID- 24684960
TI  - Pretreatment tables predicting pathologic stage of locally advanced prostate
      cancer.
AB  - BACKGROUND: Pretreatment tables for the prediction of pathologic stage have been
      published and validated for localized prostate cancer (PCa). No such tables are
      available for locally advanced (cT3a) PCa. OBJECTIVE: To construct tables
      predicting pathologic outcome after radical prostatectomy (RP) for patients with
      cT3a PCa with the aim to help guide treatment decisions in clinical practice.
      DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective cohort
      study including 759 consecutive patients with cT3a PCa treated with RP between
      1987 and 2010. INTERVENTION: Retropubic RP and pelvic lymphadenectomy. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were divided into pretreatment
      prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These
      parameters were used to construct tables predicting pathologic outcome and the
      presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal
      logistic regression. RESULTS AND LIMITATIONS: In the model predicting pathologic
      outcome, the main effects of biopsy GS and pretreatment PSA were significant. A
      higher GS and/or higher PSA level was associated with a more unfavorable
      pathologic outcome. The validation procedure, using a repeated split-sample
      method, showed good predictive ability. Regression analysis also showed an
      increasing probability of positive LNs with increasing PSA levels and/or higher
      GS. Limitations of the study are the retrospective design and the long study
      period. CONCLUSIONS: These novel tables predict pathologic stage after RP for
      patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be
      used to guide decision making in men with locally advanced PCa. PATIENT SUMMARY:
      Our study might provide physicians with a useful tool to predict pathologic stage
      in locally advanced prostate cancer that might help select patients who may need
      multimodal treatment.

PMID- 24684961
TI  - Observation of ovarian cancer stem cell behavior and investigation of potential
      mechanisms of drug resistance in three-dimensional cell culture.
AB  - Cancer cells behave differently in a three-dimensional (3D) cell culture compared
      with in the conventional two-dimensional (2D) one. Accumulated evidences indicate
      that the characteristics of cancer stem cells (CSCs) are different from common
      cancer cells due to their ability to produce tumors and resist chemoradiation.
      The objective of this work was to observe CSC behavior and investigate the
      potential mechanisms of CSC drug resistance in 3D versus 2D in vitro environment.
      We first demonstrated that the CD44(+)CD117(+)cells isolated from the human
      epithelial ovarian cancer HO8910 cell line have the properties of CSCs that
      revealed faster growth, larger tumorsphere and stronger survival potential in the
      hypoxic environment in 3D cell culture as well as more powerful tumorigenicity in
      a xenograft mice than the HO8910 cells. The CD44(+)CD117(+)CSCs also exhibited
      high chemoresistance to anticancer drugs when the cells were incubated with 5
      fluorouracil, cisplatin and carboplatin, respectively in 3D versus 2D
      environment. This might be associated with the high expression of ABCG2, ABCB1
      and the high expression of MMP-2 and MMP-9 in CD44(+)CD117(+)CSCs. Overall, these
      results suggest the advantages of using 3D culture model to accurately display
      CSC behavior in vitro. 3D model may improve the efficacy of screening anticancer
      drugs for treatment of ovarian CSCs.

PMID- 24684962
TI  - Asthma medication use among U.S. adults 18 and older.
AB  - BACKGROUND: Asthma is a chronic lung disease that currently affects an estimated
      25 million Americans. One way to control the disease is by regular use of
      preventive asthma medications and controlled use of acute medications. However,
      little is known about adults with asthma and factors associated with their
      medication use. OBJECTIVE: To identify factors associated with asthma medication
      use among U.S. adults aged 18 and older. METHODS: Data were obtained from the
      2006 to 2010 Medical Expenditure Panel Survey (MEPS). Medication use outcome
      variables include: a) daily use of a preventive asthma medication (yes/no) and b)
      overuse (3+) of acute inhalers in last 3 months (yes/no). The Andersen Behavioral
      Model of Health Care was used to guide the selection of independent variables.
      The independent variables were categorized as predisposing, enabling and medical
      need factors. Logistic regression models were used to examine the relationship
      between asthma medication use in adults with asthma. Point estimates were
      weighted to the U.S. non-institutionalized population, and standard errors were
      adjusted to account for the complex survey design. RESULTS: Compared to Whites,
      minority adults 18 and older were less likely to use preventive asthma medication
      daily (Hispanic-OR: 0.72, CI: 0.54-0.96; African American-OR: 0.62, CI: 0.51-0.75
      respectively). Similarly, Hispanic adults age 18 and older were at a
      significantly higher likelihood of overusing rescue medications compared to
      Whites (OR: 1.47, CI: 1.03-2.11). Non-metropolitan adults age 18 and older were
      more likely to overuse acute asthma medications than those from Metropolitan
      Statistical Area (OR: 1.57, CI: 1.15-2.16). Compared to older adults age 65 and
      over, late mid-life 50-64 year old adults were less likely to use a daily
      preventive asthma medication (OR: 0.67, CI: 0.54-0.83). CONCLUSIONS: Race,
      rurality and age were important factors associated with poor asthma medication
      use in U.S. adults. Although this is a first step toward identifying factors that
      may influence the use of asthma medications, future studies are needed to develop
      and implement interventions to overcome issues to improve asthma care.

PMID- 24684963
TI  - COX-2-derived endocannabinoid metabolites as novel inflammatory mediators.
AB  - Cyclooxygenase-2 (COX-2) is an enzyme that plays a key role in inflammatory
      processes. Classically, this enzyme is upregulated in inflammatory situations and
      is responsible for the generation of prostaglandins (PGs) from arachidonic acid
      (AA). One lesser-known property of COX-2 is its ability to metabolize the
      endocannabinoids, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2
      AG). Endocannabinoid metabolism by COX-2 is not merely a means to terminate their
      actions. On the contrary, it generates PG analogs, namely PG-glycerol esters (PG
      G) for 2-AG and PG-ethanolamides (PG-EA or prostamides) for AEA. Although the
      formation of these COX-2-derived metabolites of the endocannabinoids has been
      known for a while, their biological effects remain to be fully elucidated.
      Recently, several studies have focused on the role of these PG-G or PG-EA in
      vivo. In this review we take a closer look at the literature concerning these
      novel bioactive lipids and their role in inflammation. 

PMID- 24684964
TI  - Comparison of methods to quantify posterior capsule opacification using forward
      and backward light scattering.
AB  - PURPOSE: To compare forward and backward light scattering measurements to
      quantify posterior capsule opacification (PCO). SETTING: Vienna Institute for
      Research in Ocular Surgery, Vienna, Austria. DESIGN: Prospective single-center
      study. METHODS: This observational study comprised consecutive patients scheduled
      for neodymium:YAG (Nd:YAG) capsulotomy for regeneratory PCO. The corrected
      distance visual acuity (CDVA) using Early Treatment of Diabetic Retinopathy Study
      charts and the contrast sensitivity under mesopic and photopic conditions using
      Pelli-Robson charts were assessed before an Nd:YAG capsulotomy was performed.
      Retroillumination images, rotating Scheimpflug scans (Pentacam HR), and
      straylight meter (C-Quant) and point-spread function (PSF) meter (Optical Quality
      Analysis System) measurements were performed before and after Nd:YAG capsulotomy.
      RESULTS: The study enrolled 50 eyes of 50 patients. The mean uncorrected distance
      visual acuity and CDVA were 0.76 logMAR +/- 0.18 (SD) and 0.68 +/- 0.2 logMAR,
      respectively. The mean log contrast sensitivity (logCS) was 1.2 +/- 0.15 logCS
      under photopic conditions and 1.05 +/- 0.15 logCS under mesopic conditions. There
      was a moderate correlation between the Scheimpflug score and the Automated
      Quantification of After-Cataract score (r(2) = 0.37, P=.03). Furthermore, a
      moderate and close to significant correlation between the PSF meter and the
      straylight meter was observed (r(2) = 0.32; P=.07). CONCLUSION: Each of the 4
      devices assesses different aspects of a patient's quality of vision. Further
      developments should focus on methods that measure forward scatter of light in a
      large visual angle and are not too patient or examiner dependent.

PMID- 24684965
TI  - Temperature in the anterior chamber during phacoemulsification.
AB  - PURPOSE: To evaluate changes in the aqueous humor temperature using 2
      phacoemulsification units (Stellaris 28.5 kHz device and Whitestar Signature 40
      kHz device). SETTING: Nippon Medical School, Musashikosugi Hospital, Kawasaki
      City, Kanagawa, Japan. DESIGN: Experimental study. METHODS: Aqueous humor
      temperatures were measured with a temperature probe set in the anterior chamber
      during ultrasound (US) oscillation in porcine eyes under 5 conditions. RESULTS:
      Continuous longitudinal oscillation caused a rapid rise in aqueous humor
      temperature, while the pulse and elliptical modes suppressed temperature
      elevation. Reducing the number of US tip vibrations did not reduce the
      temperature in the anterior chamber. However, raising the vacuum setting allowed
      the aspirations to rise to the set value, thereby lowering the temperature in the
      anterior chamber. CONCLUSION: Because differences in the phacoemulsification
      settings can lead to temperature elevations in the anterior chamber, surgeons
      must carefully monitor these settings to prevent corneal tissue damage.

PMID- 24684966
TI  - Toric intraocular lens implantation versus astigmatic keratotomy to correct
      astigmatism during phacoemulsification.
AB  - PURPOSE: To compare toric intraocular lens (IOL) implantation and astigmatic
      keratotomy (AK) in correction of astigmatism during phacoemulsification. SETTING:
      Tertiary care hospital. DESIGN: Prospective randomized trial. METHODS:
      Consecutive patients with visually significant cataract and moderate astigmatism
      (1.25 to 3.00 diopters [D]) were randomized into 2 groups. Temporal clear corneal
      2.75 mm phacoemulsification with toric IOL implantation was performed in the
      toric IOL group and with 30-degree coupled AK at the 7.0 mm optic zone in the
      keratotomy group. The uncorrected (UDVA) and corrected (CDVA) distance visual
      acuities, refraction, keratometry, topography, central corneal thickness, and
      endothelial cell density were evaluated preoperatively and 1 day, 1 week, and 1
      and 3 months postoperatively. RESULTS: The study enrolled 34 eyes (34 patients),
      17 in each group. There was no difference in UDVA or CDVA between the 2 groups at
      any follow-up visit. The mean preoperative and postoperative refractive cylinder
      was 2.00 D +/- 0.49 (SD) and 0.33 +/- 0.17 D, respectively, in the toric IOL
      group and 1.95 +/- 0.47 D and 0.57 +/- 0.41 D, respectively, in the keratotomy
      group (P=.10). The mean residual astigmatism at 3 months was 0.44 +/- 1.89 @ 160
      in the toric IOL group and 0.77 +/- 1.92 @ 174 in the keratotomy group (P=.61).
      All eyes in the toric IOL group and 14 eyes (84%) in the keratotomy group
      achieved a residual refractive cylinder of 1.00 D or less (P=.17). CONCLUSION:
      Toric IOL implantation was comparable to AK in eyes with moderate astigmatism
      having phacoemulsification.

PMID- 24684967
TI  - Acute intraoperative rock-hard eye syndrome and its management.
AB  - PURPOSE: To evaluate the use of pars plana needle aspiration of retrolenticular
      fluid in the immediate management of an acute intraoperative rock-hard eye
      syndrome (AIRES). SETTING: Private practice, Sydney, Australia. DESIGN:
      Retrospective case series. METHODS: Data over an 18-month period were collected
      to evaluate efficacy, complications, and visual outcomes in patients who had pars
      plana needle aspiration for management of AIRES, which is an acute intraoperative
      shallowing of the anterior chamber and a marked increase in intraocular pressure
      (IOP) during phacoemulsification cataract surgery but without evidence of a
      choroidal hemorrhage. Preoperative and postoperative (1 day, 1 week, and 1 month)
      data were evaluated. Resolution of AIRES and postoperative posterior segment
      status, IOP, and corrected distance visual acuity (CDVA) were the main outcome
      measures. RESULTS: Acute intraoperative rock-hard eye syndrome occurred in 6
      (1.45%) of 413 surgeries. All 6 patients were women with a mean age of 81 years.
      Four patients had dense nuclear cataracts. In each case, the anterior chamber
      depth and IOP normalized immediately after pars plana needle aspiration and the
      procedure concluded uneventfully. Mild vitreous hemorrhage was observed in 1
      patient postoperatively. At 1 month, the IOP was normal in 5 of 6 cases, while
      the CDVA was 20/12 in 5 of 6 cases. CONCLUSION: Although the etiology of AIRES is
      iatrogenic, immediate resolution was achieved uneventfully with pars plana needle
      aspiration, which appears to be a safe management technique with satisfactory
      outcomes.

PMID- 24684969
TI  - Single cell genomics of deep ocean bacteria.
AB  - SAR11 is one of the most abundant bacterioplanktons in the upper surface waters
      of the oceans. In a recent issue of The ISME Journal, Thrash and colleagues
      present the genomes of four single SAR11 cells isolated from the deep oceans that
      are enriched in genes for membrane biosynthetic functions. 

PMID- 24684968
TI  - Anthrax lethal and edema toxins in anthrax pathogenesis.
AB  - The pathophysiological effects resulting from many bacterial diseases are caused
      by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming
      bacterium, is such a pathogen, causing anthrax through a combination of bacterial
      infection and toxemia. B. anthracis causes natural infection in humans and
      animals and has been a top bioterrorism concern since the 2001 anthrax attacks in
      the USA. The exotoxins secreted by B. anthracis use capillary morphogenesis
      protein 2 (CMG2) as the major toxin receptor and play essential roles in
      pathogenesis during the entire course of the disease. This review focuses on the
      activities of anthrax toxins and their roles in initial and late stages of
      anthrax infection. 

PMID- 24684971
TI  - Histological evaluation of mandibular third molar roots retrieved after
      coronectomy.
AB  - There is a resurgence of interest in coronectomy for the management of mandibular
      third molars because it has a low risk of injury to the inferior dental nerve.
      However, there is concern that the root that is left in place will eventually
      become a source of infection. We describe the histological evaluation of 26
      consecutive symptomatic coronectomy roots in 21 patients. All roots had vital
      tissue in the pulp chamber and there was no evidence of periradicular
      inflammation. Persistent postoperative symptoms related predominantly to
      inflammation of the soft tissue, which was caused by partially erupted roots or
      failure of the socket to heal. 

PMID- 24684970
TI  - Distribution of estrogen and progesterone receptors isoforms in endometrial
      cancer.
AB  - BACKGROUND: 70-80% of sporadic endometrial carcinomas are defined as endometrioid
      carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually
      retain expression of estrogen and progesterone receptors (ER and PR,
      respectively), as advanced stage, poorly differentiated tumors often lack one or
      both of these receptors. Well-described EC prognosis includes tumor
      characteristics, such as depth of myometrial invasion. Therefore, in the current
      study, we evaluated the expression profile of ER and PR isoforms, including ER
      alpha, PR-A and PR-B, in correlation to EC tumor histological depth. METHODS:
      Using immunohistochemistry and image analysis software, the expression of ER
      alpha, PR-A, PR-B and Ki67 was assessed in endometrial stroma and epithelial
      glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC
      specimens, and compared to 5 biopsies of non-malignant endometrium. RESULTS:
      Expression of PR-A and ER-alpha was found to be lower in EC compared to
      nonmalignant tissue, as the stromal expression was dramatically reduced compared
      to epithelial cells. Expression ratios of both receptors were significantly high
      in superficial and deep portions of EC; in non-tumoral portion of EC were close
      to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial
      glands of EC superficial and deep portions, and high in the extra-tumoral region.
      Elevated PR-B expression was found in stroma of EC, as well. CONCLUSIONS: The
      ratio of ER-alpha and PR-A expression in the epithelial glands and the stroma of
      EC biopsies may serve as an additional parameter in the histological evaluation
      of EC tumor. VIRTUAL SLIDES: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016.

PMID- 24684972
TI  - Drug dosage in isolated limb perfusion: evaluation of a limb volume model for
      extremity volume calculation.
AB  - BACKGROUND: Exact drug dosing in isolated limb perfusion (ILP) and infusion (ILI)
      is essential. We developed and evaluated a model for calculating the volume of
      extremities and compared this model with body weight- and height-dependent
      parameters. METHODS: The extremity was modeled by a row of coupled truncated
      cones. The sizes of the truncated cone bases were derived from the circumference
      measurements of the extremity at predefined levels (5 cm). The resulting volumes
      were added. This extremity volume model was correlated to the computed tomography
      (CT) volume data of the extremity (total limb volume). The extremity volume was
      also correlated with the patient's body weight, body mass index (BMI) and ideal
      body weight (IBW). The no-fat CT limb volume was correlated with the
      circumference-measured limb volume corrected by the ideal-body-weight to actual
      body-weight ratio (IBW corrected-limb-volume). RESULTS: The correlation between
      the CT volume and the volume measured by the circumference was high and
      significant. There was no correlation between the limb volume and the bare body
      weight, BMI or IBW. The correlation between the no-fat CT volume and IBW
      corrected limb volume was high and significant. CONCLUSIONS: An appropriate drug
      dosing in ILP can be achieved by combining the limb volume with the simple
      circumference measurements and the IBW to body-weight ratio.

PMID- 24684973
TI  - Fingolimod therapy in early multiple sclerosis: an efficacy analysis of the
      TRANSFORMS and FREEDOMS studies by time since first symptom.
AB  - AIMS: The phase 3 TRANSFORMS and FREEDOMS studies established the efficacy of
      fingolimod in reducing multiple sclerosis (MS) relapses and magnetic resonance
      imaging lesions compared with intramuscular (IM) interferon (IFN) beta-1a and
      placebo over 12 and 24 months, respectively. METHODS: To investigate the efficacy
      of fingolimod at the approved 0.5 mg dose in patients early in the MS disease
      course, post hoc subgroup analyses of TRANSFORMS (n = 272) and FREEDOMS (n = 217)
      data were conducted in patients who experienced their first MS symptom <3 years
      before randomization. RESULTS: Fingolimod 0.5 mg reduced annualized relapse rate
      by 73.4% (P = 0.0002) versus IFNbeta-1a IM and by 67.4% (P < 0.0001) versus
      placebo in patients with <3 years since first symptom; respective reductions were
      45.4% and 51.4% in subgroups of patients with >=3 years since first symptom. For
      patients with <3 years since their first symptom, significantly fewer new/newly
      enlarged T2 lesions were observed with fingolimod versus IFNbeta-1a IM (mean
      number, 1.94 vs. 2.95; P = 0.036) or placebo (4.1 vs. 10.7; P < 0.001); the mean
      number of gadolinium-enhancing T1 lesions was significantly reduced versus
      placebo (0.3 vs. 1.1; P < 0.001). CONCLUSION: Fingolimod 0.5 mg is highly
      effective in reducing relapses and MRI activity in patients early in the MS
      disease course.

PMID- 24684974
TI  - Risk of coronary artery disease in patients with idiopathic inflammatory
      myopathies: a systematic review and meta-analysis of observational studies.
AB  - OBJECTIVES: To investigate the risk of coronary artery disease in patients with
      idiopathic inflammatory myopathies (IIM). METHODS: We conducted a systematic
      review and meta-analysis of observational studies that reported odds ratios,
      relative risks, hazard ratios, or standardized incidence ratios comparing the
      risk of coronary artery disease in patients with IIM versus non-IIM participants.
      We searched published studies indexed in MEDLINE, EMBASE, and the Cochrane
      database from inception to December 2013 using the terms "coronary artery
      disease" OR "coronary heart disease" OR "myocardial infarction" OR
      "atherosclerosis" combined with the terms "dermatomyositis" OR "polymyositis" OR
      "Idiopathic inflammatory myopathy." Pooled risk ratio and 95% confidence interval
      were calculated using a random-effect, generic inverse variance method. RESULT:
      Overall, four studies were identified and included for data analysis. The pooled
      risk ratio of CAD in patients with IIM was 2.24 (95% CI: 1.02-4.92). The
      statistical heterogeneity of this meta-analysis was high with an I(2) of 97%.
      CONCLUSION: Our study demonstrated a statistically significant increased risk of
      CAD among patients with IIM.

PMID- 24684975
TI  - Palmar fasciitis and polyarthritis syndrome-systematic literature review of 100
      cases.
AB  - OBJECTIVE: To analyse clinical, laboratory, and imaging characteristics of all
      patients with palmar fasciitis and polyarthritis syndrome (PFPAS) described in
      the literature. METHOD: Comparison of the clinical presentation of one patient
      with acute onset of PFAPS with 99 other published cases identified through a
      PubMed literature research. RESULTS: Since the original description in 1982 by
      Medsger et al., there have been numerous case reports and small case series in
      the literature. In total, 73 articles in English, French and Spanish language
      were included in the analysis. PFPAS is a rare but characteristic paraneoplastic
      syndrome in rheumatology. Its distinct clinical feature is a painful swelling of
      both the hands caused by an inflammation of the palmar fascia, tendon sheaths and
      small joints of fingers and wrist, and flexion contractures develop rapidly.
      Since the subcutaneous tissues become indurated and hard, the illustrative term
      "woody hands" was coined. The most frequent underlying malignancy is ovarian
      cancer but adenocarcinomas of the breast, gastrointestinal tract and other organs
      can also cause this syndrome. A helpful diagnostic procedure in order to identify
      the nature of the underlying malignancy in many cases has been the determination
      of various serum tumour markers. In cases when a complete removal of the
      malignancy is possible, PFPAS can also undergo complete remission. CONCLUSIONS:
      Knowledge of the distinct features of this rare paraneoplastic syndrome
      facilitates early diagnosis and potentially life-saving therapeutic
      interventions.

PMID- 24684976
TI  - High incidence of stroke in young women with sleep apnea syndrome.
AB  - OBJECTIVE: Patients with sleep apnea syndrome (SAS) carry a higher stroke risk.
      The differential stroke risk between sex and among different age groups has not
      yet been specifically addressed in previous studies. METHODS: Using a universal
      insurance claims database, we identified a large cohort of SAS patients from 1997
      to 2010 and assessed the sex- and age-specific stroke risk compared with a
      control cohort matched for age, sex, and index date. Cox regression analyses were
      performed to assess the hazard ratio (HR) of stroke and the corresponding 95%
      confidence interval (CI). Stroke-free probabilities were computed using the
      Kaplan-Meier method and differences between both cohorts were examined using the
      log-rank test. RESULTS: We identified 29,961 patients with SAS and a control
      cohort of 119,844 subjects without SAS. The overall incidence of stroke in the
      SAS cohort was 37% higher compared to the non-SAS cohort (54.6 per 10,000
      individual-years vs 39.8 per 10,000 individual-years). After controlling for sex
      and comorbidities, the SAS cohort exhibited a 19% higher risk for stroke compared
      to the control cohort (adjusted HR, 1.19 [95% CI, 1.09-1.30]). Women with SAS
      ages 35 years or younger had the highest stroke risk compared to older age groups
      of the same sex and their risk for stroke was relatively higher compared to their
      male counterparts. CONCLUSION: Women aged 35 years or younger with SAS have a
      higher stroke risk.

PMID- 24684977
TI  - Use of sleep medication in children with ADHD.
AB  - OBJECTIVE: Sleep problems are common in children with attention
      deficit/hyperactivity disorder (ADHD), yet little is known about sleep medication
      use in this population. The aim of this study was to describe sleep medication
      use, as well as associated child and family characteristics in school-aged
      children with ADHD. METHOD: Sleep medication use was ascertained using a
      prospective parent-completed seven-night sleep and medication log. Exposure
      variables included socio-demographic characteristics, total sleep problem
      severity (Children's Sleep Habits Questionnaire), ADHD severity and subtype (ADHD
      Rating Scale IV), ADHD medication use, internalising and externalising co
      morbidities (Anxiety Disorders Interview Schedule for Children/Parent version IV)
      and parent mental health (Depression Anxiety Stress Scale). RESULTS: Two hundred
      and fifty-seven children with ADHD participated and of these 57 (22%) were taking
      sleep medication (melatonin 14% and clonidine 9%). Sleep medication use was
      associated with combined-type ADHD and ADHD medication use. The presence of co
      occurring internalising and externalising co-morbidities was also associated with
      sleep medication use in ad hoc analyses. CONCLUSION: Sleep medication use is
      common in children with ADHD and is associated with combined-type ADHD and use of
      ADHD medication. Further research is needed on the broad functional benefits and
      long-term safety of sleep medication in this population.

PMID- 24684978
TI  - Sleep-disordered breathing does not affect nocturnal dipping, as assessed by
      pulse transit time, in preschool children: evidence for early intervention to
      prevent adverse cardiovascular effects?
AB  - OBJECTIVE: Sleep-disordered breathing (SDB) is associated with reduced nocturnal
      dipping of blood pressure (BP) and sleep disruption in adults, and these features
      confer an increased risk of cardiovascular events. As SDB prevalence in children
      peaks during the preschool years, we investigated nocturnal dipping and sleep
      fragmentation in preschool children with SDB. METHODS: Children (3-5 years;
      n=163) grouped by obstructive apnoea hypopnoea index (OAHI): control, no snoring
      history and OAHI <=1 event/h; primary snoring, OAHI <=1 event/h; mild SDB, >1-<=5
      events/h; moderate-severe SDB, >5 events/h. Pulse transit time (PTT), an inverse
      continuous indicator of BP changes, and heart rate (HR) during total sleep time
      and the first period of rapid eye movement (REM), non-REM (NREM)1/2 and NREM3/4
      sleep were expressed as percentage change from wake before sleep onset. The sleep
      fragmentation index (SFI) was calculated as the number of sleep stage transitions
      or awakenings per hour of sleep. RESULTS: There were no group differences in the
      change in PTT or HR from wake to total sleep time or to individual sleep stages
      or in the proportion of children in the quartile with the smallest change in PTT
      during total sleep. Children with moderate-severe SDB had higher SFI than primary
      snoring (PS) or mild SDB groups (p<0.05 for both) and controls (p=0.07).
      CONCLUSIONS: In contrast to adults, nocturnal dipping is preserved in young
      children with SDB, despite increased sleep fragmentation. As there is evidence
      that nocturnal dipping is similarly preserved at the school age, childhood may
      pose a window of opportunity for resolution of SDB when the cardiovascular
      effects are less marked.

PMID- 24684980
TI  - Who should be an author on your academic paper?

PMID- 24684979
TI  - Vitamin D levels and obstructive sleep apnoea in children.
AB  - AIMS/HYPOTHESIS: Obstructive sleep apnoea (OSA) is a common health problem in
      children. African American (AA) and obese children have higher prevalence of OSA,
      and are also at a higher risk of reduced vitamin D levels. We hypothesised that
      OSA would be associated with lower levels of plasma 25-hydroxyvitamin D (25(OH)D)
      and increase in the risk of metabolic dysfunction and systemic inflammation.
      METHODS: In this observational cross-sectional study, 176 prospectively recruited
      children (mean age: 6.8+/-0.8 years) underwent overnight polysomnographic
      evaluation and a fasting blood draw the morning after the sleep study. In
      addition to lipid profile, homeostatic model of insulin resistance (HOMA-IR) and
      high-sensitivity C-reactive protein (hsCRP) assays and plasma 25(OH)D levels were
      assessed using ELISA kits. RESULTS: AA children, obese children and children with
      OSA had significantly lower 25(OH)D levels. Linear associations emerged between
      25(OH)D plasma levels and body mass index (BMI) z-score, hsCRP and HOMA-IR, as
      well as with apnoea-hypopnoea index (AHI) and oxygen saturation (SpO2) nadir, the
      latter two associations remaining statistically significant even when controlling
      for all other potential confounders, and independently accounting for 17.7% of
      the variance in 25(OH)D (p<0.01). CONCLUSIONS: 25(OH)D levels are reduced in
      paediatric OSA, in AA children and in obese children, particularly when all are
      present, and may play a role in modulating the degree of insulin resistance and
      systemic inflammation. The short-term and long-term significance of reduced
      25(OH)D in paediatric OSA remains undefined.

PMID- 24684981
TI  - [Translation medicine in wound healing: successful cases and personal
      deliberation].
AB  - Local wound care is the key step in wound management, and it is affected by many
      factors. The innovation and translation application of some new theories and
      skills may help accelerate local wound healing velocity and improve wound healing
      quality. In this paper, the translation medicine in wound healing, such as
      debridement, dressings, and tissue engineering products, are reviewed. In the
      meantime, personal consideration concerning their successful and future
      development is given. 

PMID- 24684982
TI  - [An inquiry into the relevant issues about burn sepsis].
AB  - Since the definition of sepsis was proposed in Chest by American College of Chest
      Physicians and Society of Critical Care Medicine in 1992, researches on burn
      sepsis have focused on the regulation of immune-inflammation response resulting
      in minimizing tissue injury resulted from excessive inflammatory response.
      Treatment of sepsis should focus on effect of early circulation oxygenation
      support in preventing and treating multiple organ dysfunction. The hypothesis of
      producing a hibernation-like state which might prevent multiple organ dysfunction
      in patients with sepsis provides us a new therapeutic strategy in protecting
      organs in the early stage of sepsis in future. 

PMID- 24684983
TI  - [Analysis of drug resistance of Pseudomonas aeruginosa and use of antibiotics in
      burn wards during 6 years].
AB  - OBJECTIVE: To study the distribution characteristics of pathogens, the drug
      resistance of Pseudomonas aeruginosa (PA), and the use of antibiotics against
      Gram negative bacilli (GNB) in burn wards, so as to provide a guide for future
      treatment. METHODS: A total of 2 758 strains of pathogens were isolated from
      specimens of wound excretion, venous catheter attachment, blood, stool, urine,
      and sputum from 7 441 patients hospitalized in our burn wards from January 2007
      to December 2012. After being identified by API strips and automatic
      microorganism identification and drug sensitivity analyzer, drug resistance of
      all the pathogens to 13 antibiotics commonly used in clinic, including amikacin,
      cefoperazone/sulbactam, ceftazidime, etc., was tested by K-B paper disk diffusion
      method. The defined daily doses per 1 000 patient-day of 5 antibiotics including
      amikacin, cefoperazone/sulbactam, ceftazidime, imipenem, and ciprofloxacin each
      year was set as use intensity. The WHONET 5.6 software was used to analyze the
      distribution of pathogens and the drug resistance of PA to 13 antibiotics. The
      SPSS 19.0 software was used to analyze the relation between changes in drug
      resistant rates of PA to 13 antibiotics and year, the relation between the
      proportion of PA in all the pathogens and the use intensity of 5 antibiotics
      commonly used against GNB, and the relation between the use intensity of
      ciprofloxacin and the change in drug-resistant rates of PA to amikacin,
      cefoperazone/sulbactam, and imipenem with Pearson correlation analysis. RESULTS:
      (1) In 6 years, Staphylococcus aureus ranked the first with the highest
      proportion (31%, 865/2 758). The proportion of PA increased to tie in with
      Acinetobacter baumannii (both accounting for 17%, 458/2 758), both taking the
      second place. (2) Drug-resistant rates of PA to amikacin, gentamicin, aztreonam,
      piperacillin, cefoperazone, cefepime, piperacillin/tazobactam,
      cefoperazone/sulbactam, imipenem, and meropenem were significantly increased and
      positively correlated with year (with r values from 0.844 to 0.988, P < 0.05 or P
      < 0.01), while the drug-resistant rate of PA to ciprofloxacin was decreased and
      negatively correlated with year (r = -0.836, P < 0.05). (3) In 6 years, the use
      intensity of amikacin (from 8.65 to 91.44), cefoperazone/sulbactam (from 9.62 to
      63.56), imipenem (from 7.63 to 157.25), ceftazidime (from 18.39 to 86.11), and
      ciprofloxacin (from 0 to 19.77) was increased. (4) The proportion of PA in all
      the pathogens was positively correlated with the use intensity of imipenem and
      ciprofloxacin (with r values respectively 0.849, 0.933, P < 0.05 or P < 0.01),
      while it was not significantly correlated with the use intensity of amikacin,
      cefoperazone/sulbactam, or ceftazidime (with r values respectively 0.672, 0.668,
      0.794, P values all above 0.05). (5) The use intensity of ciprofloxacin was
      positively correlated with the drug-resistant rates of PA to amikacin,
      cefoperazone/sulbactam, and imipenem (with r values respectively 0.878, 0.934,
      0.928, P < 0.05 or P < 0.01). CONCLUSIONS: In our burn wards, drug-resistant PA
      was prevalent, with positive correlation with the use intensity of antibiotics.
      The sensitive rate can be increased by a decrease in the use of amikacin,
      cefoperazone/sulbactam, and imipenem periodically.

PMID- 24684984
TI  - [Analysis of the resistance mechanism and homology of carbapenems-resistant
      Pseudomonas aeruginosa].
AB  - OBJECTIVE: To study the resistance mechanism and homology of carbapenems
      resistant Pseudomonas aeruginosa (PA). METHODS: A total of 812 strains of PA
      (identified) were isolated from sputum, urine, blood, pus, and drainage of
      patients with burn, severe pneumonia, diabetes, chronic obstructive pneumonia,
      myocarditis, liver transplantation, or brainstem hemorrhage hospitalized from
      January to September 2012. Drug resistance of the 812 strains of PA to 15
      antibiotics commonly used in clinic, including piperacillin, imipenem, etc., was
      tested using the automatic microorganism identifying and drug sensitivity
      analyzer. Among the carbapenems-resistant PA isolates, synergism test with
      imipenem-ethylene diamine tetraacetic acid (EDTA) and enhancement test with
      imipenem-EDTA and ceftazidime-EDTA were used to screen metallo-beta-lactamase
      (MBL)-producing strains; modified Hodge test was used to screen strains producing
      Klebsiella pneumoniae carbapenemases (KPC); the carbapenemase gene, plasmid
      mediated quinolone resistant (PMQR) gene, and mobile genetic elements (MGE) were
      detected by polymerase chain reaction (PCR). In addition, a comparative analysis
      of the PMQR gene carrying level between the carbapenemase gene positive strains
      and carbapenemase gene negative strains was carried out. The repetitive consensus
      sequence of Enterobacteriaceae genome PCR (ERIC-PCR) was carried out for gene
      typing. Moreover, the source and resistance genes of strains with the same
      genotype were analyzed. Data were processed with Fisher's exact probability test.
      RESULTS: The sensitive rates of the 812 strains of PA to ceftriaxone and
      trimethoprim-sulfamethoxazole were high, respectively 83.07% and 88.19%, and
      those of the other antibiotics ranged from 17.30% to 55.18%. Twenty-four
      carbapenems-resistant PA strains were screened, including 11 MBL-producing
      strains and 2 KPC-producing strains. Eleven carbapenems-resistant PA strains were
      found to harbor the blaVIM-2 gene, accounting for 45.83%; 2 carbapenems-resistant
      PA strains carried the blaKPC-2 gene, accounting for 8.33%. Fourteen carbapenems
      resistant PA strains only harbored the PMQR gene acc (6')-Ib-cr, accounting for
      58.33%; 3 carbapenems-resistant PA strains (12.50%) harbored the PMQR genes acc
      (6')-Ib-cr and qnr, including 1 strain with qnr A1 and 2 strains with qnr B4. Ten
      carbapenems-resistant PA strains carried the MGE gene ISCR1, accounting for
      41.67%; 6 carbapenems-resistant PA strains carried the MGE gene ISEcp1,
      accounting for 25.00%. In addition, 3 carbapenems-resistant PA strains co
      harbored the MGE genes ISCR1 and ISEcp1 (accounting for 12.50%), while only 1
      carbapenems-resistant PA strain co-harbored the MGE genes class 1 integron and
      ISEcp1, accounting for 4.17%. Twelve out of the 13 carbapenemase gene positive
      strains carried one or two PMQR gene (s), which was significantly higher than
      that of the carbapenemase gene negative strains (with only five strains harboring
      one PMQR gene, P = 0.023). The 24 carbapenems-resistant PA strains were
      classified into 6 genotypes by the ERIC-PCR. Thirteen strains (accounting for
      54.17%), mainly isolated from pus and blood samples, which were collected from
      burn department, were in genotype A. Eight out of the 13 strains harbored genes
      blaVIM-2, acc (6')-Ib-cr, and ISCR1. Five strains (accounting for 20.83%), mainly
      isolated from sputum samples which were collected from ICU, were in genotype B.
      Only 2 out of the 5 strains co-harbored the carbapenemase gene, PMQR gene, and
      MGE gene. There were respectively 2 strains in genotypes C and D, both accounting
      for 8.33%; the strains in different pattern were isolated from different wards,
      and they harbored diverse resistance genes. There were respectively 1 strain in
      genotypes E and F, both accounting for 4.17%. CONCLUSIONS: The resistance
      mechanism of PA to carbapenems is mainly mediated by the VIM-2 type MBL in our
      hospital during 2012, followed by KPC-2 type carbapenemase, and the prevalent
      genotype is type A. The carbapenemase genes and PMQR genes co-carrying phenomenon
      exists among these strains of PA, which disseminated by clones.

PMID- 24684985
TI  - [Investigation of antibacterial activity of topical antimicrobials against
      methicillin-resistant Staphylococcus aureus].
AB  - OBJECTIVE: To investigate the antibacterial activity of silver sulfadiazine (SD
      Ag), mupirocin, and clotrimazole used alone or in combination against methicillin
      resistant Staphylococcus aureus (MRSA) isolated from burn wounds. METHODS:
      Eighteen MRSA isolates from wound excretion of 18 burn patients hospitalized in
      our unit from July to December 2011 were collected continuously and non
      repetitively. (1) Minimum inhibitory concentration (MIC), 50% MIC (MIC50), and
      90% MIC (MIC90) of SD-Ag, mupirocin, and clotrimazole used alone, those of SD-Ag
      and mupirocin used in combination, and those of SD-Ag, mupirocin, and
      clotrimazole used in combination to MRSA were determined by checkerboard agar
      dilution method. (2) Fractional inhibitory concentration (FIC) index was
      calculated to determine the combined effect of SD-Ag plus mupirocin, and SD-Ag
      plus mupirocin and clotrimazole. Synergy with FIC index less than or equal to 0.5
      or additivity with FIC index more than 0.5 and less than or equal to 1.0 was
      regarded as effective, and indifference with FIC index more than 1.0 and less
      than or equal to 4.0 or antagonism with FIC index more than 4.0 was regarded as
      ineffective. The effective ratio was compared with overall ratio (assumed as 0)
      by unilateral binomial distribution test. RESULTS: The MIC, MIC50, and MIC90 of
      SD-Ag, mupirocin, and clotrimazole used alone against 18 MRSA isolates were
      respectively 8, 8, 16 ug/mL; 2, 16, 64 ug/mL; 2, 2, 2 ug/mL. MIC of antimicrobial
      agents used in combination decreased from 3.1% to 50.0% as compared with that of
      individual agent used alone. Compared with those of single application of SD-Ag
      and mupirocin, MIC50 of SD-Ag and that of mupirocin both decreased 75.0%, and
      MIC90 of them decreased 87.5% when SD-Ag and mupirocin were used in combination.
      Compared with those of single application of SD-Ag, mupirocin, and clotrimazole,
      MIC50 of SD-Ag, mupirocin, and clotrimazole respectively decreased 75.0%, 87.5%,
      and 50.0%; MIC90 of them respectively decreased 87.5%, 96.9%, and 50.0% when SD
      Ag, mupirocin, and clotrimazole were used in combination. Among the 18 MRSA
      isolates, the combined effect of SD-Ag and mupirocin was synergic in 9 isolates,
      additive in 7 isolates, indifferent in 2 isolates, and antagonistic in 0 isolate;
      the combined effect of SD-Ag, mupirocin, and clotrimazole was additive in 16
      isolates, indifferent in 2 isolates, and antagonistic in 0 isolate. There were
      statistically significant differences between effective ratio and overall ratio
      of 18 MRSA isolates treated with combined antimicrobial agents (P values all
      above 0.01). CONCLUSIONS: For burn wounds at middle and late stages infected with
      Staphylococcus aureus or Staphylococcus aureus and Fungus, low dose of SD-Ag or
      combination of above-mentioned antimicrobial agents can effectively control
      infection and decrease the adverse effect of antimicrobial agents on wound
      healing.

PMID- 24684986
TI  - [Analysis of drug resistance and drug resistance genes of imipenem-resistant
      Pseudomonas aeruginosa strains isolated from burn wards].
AB  - OBJECTIVE: To analyze the drug resistance and drug resistance genes of imipenem
      resistant Pseudomonas aeruginosa (IRPA) strains isolated from burn wards.
      METHODS: From June 2011 to June 2012, 30 strains of IRPA were isolated from wound
      excretion, sputum, and venous catheter attachment from burn patients hospitalized
      in Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine.
      Drug resistance of the IRPA to 12 antibiotics commonly used in clinic, including
      ceftazidime, amikacin, ciprofloxacin, etc., was tested with K-B paper agar disk
      diffusion method. Metallo-beta-lactamase (MBL)-producing IRPA was detected by
      synergism test with imipenem-2-mercaptoethanol. Plasmid of IRPA was extracted,
      and it was inserted into competent cells, producing transformation strains (TSs).
      Drug resistance of TSs to imipenem and the MBL-producing TSs were detected. The
      genes blaIMP, blaVIM, blaOXA-1, blaOXA-2 and blaOXA-10 of IRPA and the TSs were
      detected by polymerase chain reaction. The drug resistance of IRPA producing MBL
      or OXA enzyme was summed up. RESULTS: The sensitive rates of the 30 strains of
      IRPA to the 12 antibiotics were equal to or above 60.0%. Six strains of MBL
      producing IRPA were screened. Twenty-four TSs were resistant to imipenem, and 6
      strains among them were MBL-producing positive. Among the 30 strains of IRPA, 6
      strains and their corresponding TSs carried blaVIM; 20 strains and their
      corresponding TSs carried blaOXA-10; no strain was detected to carry blaIMP,
      blaOXA-1 or blaOXA-2. Two strains and their corresponding TSs were detected
      carrying both blaVIM and blaOXA-10. No significant difference of drug resistance
      was observed between strains producing only MBL or OXA enzyme, with the same high
      resistance to beta-lactam antibiotics and some degree of sensitivity to
      aminoglycoside antibiotics. Strains producing enzymes MBL and OXA were all
      resistant to the 12 antibiotics. CONCLUSIONS: IRPA strains isolated from burn
      wards of Guangzhou Hospital of Integrated Traditional Chinese and Western
      Medicine are multidrug-resistant, and they mainly produce type B and D
      carbapenemases.

PMID- 24684987
TI  - [Effect of severe burn on growth and development and the level of growth hormone
      in mice].
AB  - OBJECTIVE: To analyze the changes in body growth, learning and memory
      capabilities, exercise capacity, and the level of growth hormone (GH) in mice
      suffering from severe burn. METHODS: One hundred and four healthy BALB/c mice
      aged from 3 to 4 weeks were divided into normal control group (NC, without
      treatment) , 7 s burn group (inflicted with 20%TBSA deep partial-thickness burn
      on the back), 10 s burn group (inflicted with 20%TBSA full-thickness burn on the
      back), and negative control group (simulating the treatment of two burn groups
      without injury) according to the random number table, with 26 mice in each group.
      The body weight, body length, and tail length of 8 mice in each group were
      measured before burn. Respectively 6 mice of two burn groups were sacrificed on
      post burn day (PBD) 1, 3, and 7 for determination of serum level of GH with
      enzyme-linked immunosorbent assay kit. The remaining 8 mice in each of the two
      burn groups were raised to adulthood. The body weight, body length, and tail
      length were measured on PBD 62, and the increased percentages of body weight,
      body length, and tail length were calculated. Morris water maze tests, including
      escape latency on PBD 66, 67, and 68, frequency of stepping over the platform
      location and proportion of staying time in the target quadrant on PBD 69, were
      used to examine the learning and memory capabilities. The time of loaded swimming
      and the time of pole-climbing on PBD 70 were used to assess the exercise
      capacity. Above-mentioned indexes were also determined in the two control groups
      at the same time points. Data were processed with one-way analysis of variance;
      Welch test was applied when equal variance was not assumed; independent samples t
      test was applied for paired comparison. RESULTS: (1) The level of GH of mice in 7
      s burn group on PBD 1 [(3 021 +/- 506) pg/mL] was lower than that of group NC [(3
      728 +/- 412) pg/mL, t = 2.656, P < 0.05], while on PBD 3 and 7 [(3 098 +/- 503) ,
      (3 199 +/- 275) pg/mL] they were close to those of group NC [(3 872 +/- 785), (3
      301 +/- 600) pg/mL, with t values respectively 2.033 and 0.379, P values all
      above 0.05]. The levels of GH of mice in 10 s burn group on PBD 1, 3, and 7 were
      respectively (2 859 +/- 447), (2 707 +/- 151) , and (2 666 +/- 222) pg/mL, which
      were lower than those of group NC (with t values respectively 3.504, 3.571,
      2.429, P < 0.05 or P < 0.01). (2) The increased percentage of body weight, body
      length, and tail length of mice in group NC, 7 s burn group, and 10 s burn group
      were respectively (155 +/- 22) %, (46 +/- 6) %, (63 +/- 10)%; (112 +/- 57) %, (32
      +/- 12) %, (40 +/- 15) %; (106 +/- 36) %, (30 +/- 8) %, (32 +/- 7) %. The
      increased percentage of body weight of mice in 7 s burn group was close to that
      in group NC (t = 1.997, P > 0.05), while the increased percentages of other
      indexes of mice in the two burn groups were lower than those in group NC (with t
      values from 3.092 to 6.910, P values all below 0.01). (3) The escape latency
      values of mice in 10 s burn group on PBD 67 and 68 were respectively (33 +/- 12),
      (33 +/- 11) s, which were longer than those of group NC [(20 +/- 8), (20 +/- 7)
      s, with t values respectively 2.421 and 2.692, P values all below 0.05]. The
      frequency of stepping over the platform location of mice in 10 s burn group [(1.6
      +/- 1.8) times] was close to that of group NC [(3.2 +/- 1.5) times, t = 1.989, P
      > 0.05]. The proportion of retention time in the target quadrant of mice in 10 s
      burn group [ (28 +/- 7) %] was shorter than that of group NC[(48 +/- 16)%, t =
      3.076, P < 0.01]. The escape latency of mice in 7 s burn group on PBD 67 [(30 +/-
      7) s] was longer than that of group NC (t = 2.659, P < 0.05). The frequency of
      stepping over the platform location and the proportion of retention time in the
      target quadrant of mice in 7 s burn group [(2.0 +/- 1.1) times, (36 +/- 11) %,
      respectively] were close to those of group NC (with t values respectively 1.930,
      1.670, P values all above 0.05). (4) The time of pole-climbing [(30 +/- 11) s]
      and the time of loaded swimming [(38 +/- 39) min] of mice in 10 s burn group were
      shorter than those of group NC [(47 +/- 11) s, (122 +/- 74) min, with t values
      respectively 3.108, 2.868, P < 0.05 or P < 0.01]. The time of loaded swimming of
      mice in 7 s burn group [(47 +/- 12) min] was shorter than that of group NC (t =
      2.855, P < 0.05), while the time of pole-climbing [(33 +/- 14) s] was close to
      that of group NC (t = 2.044, P > 0.05). CONCLUSIONS: For mice, severe burn can
      delay body growth, decrease the learning and memory capabilities, decrease
      exercise capacities, and reduce the serum level of GH.

PMID- 24684988
TI  - [Expression of coxsackie-adenovirus receptor in keratinocytes of mouse skin after
      heat stimulation and the effect of coxsackie-adenovirus receptor on dendritic
      epidermal T lymphocytes].
AB  - OBJECTIVE: To study the influence of heat stimulation on expression of coxsackie
      adenovirus receptor (CAR) in keratinocytes (KCs) of mouse skin and the effect of
      CAR on production of cell growth factors by dendritic epidermal T lymphocytes
      (DETCs). METHODS: (1) Twenty BALB/c mice were divided into heat stimulation group
      (HS) and control group (C) according to the random number table, with 10 mice in
      each group. Mice in group HS were inflicted with scald milder than superficial
      thickness by dressing wet hot gauze, which had been soaked in 100 degrees C hot
      water for 3 min, in the hair removed area on the back for 1 to 3 s, while mice in
      group C were sham injured by dressing a wet gauze which had been soaked in water
      of room temperature for 3 min in the hair removed area on the back for 1 to 3 s.
      Square full-thickness skin specimens measuring 2.0 cm * 2.0 cm in size were
      obtained from the center of the bare skin. The expression of CAR in skin tissue
      sections were detected by immunohistochemistry staining. The mRNA and protein
      expression levels of CAR in skin tissue sections were respectively determined by
      real-time fluorescent quantitation RT-PCR and Western blotting. (2) KCs were
      isolated and cultured from full-thickness skin obtained from the trunk of 2 fetal
      BALB/c mice, and they were divided into 2 groups according to the random number
      table, with 5 wells in each group. The cells in group HS and group C were
      respectively cultured in 42 degrees C and 37 degrees C, 5% CO2 incubator for 1 h,
      and then all the cells were cultured in 37  degrees , 5% CO2 incubator for 6 h.
      The apoptosis of the cells and their expression of CAR were detected by flow
      cytometer. (3) Five BALB/c mice were sacrificed, and full-thickness skin was
      obtained from the trunk. The DETCs were divided into 7 groups according to the
      random number table after being isolated and purified from the skin specimens.
      Cells in group C were cultured without any stimulation, and cells in the 0.5,
      1.0, 2.0, 4.0, 8.0, and 16.0 mg/L CAR groups were respectively cultured with
      corresponding concentration of recombinant mice CAR nutrient solutions, with 5
      wells in each group. The contents of insulin-like growth factor I (IGF-I) and
      keratinocyte growth factor (KGF) were determined with ELISA. Data were processed
      with independent samples t test and one-way analysis of variance. RESULTS: (1)
      The immunohistochemistry staining showed that there was mild positive staining in
      the skin tissue sections of mice in group C, while the positive staining was more
      obvious in group HS. The positive staining was mainly located in KCs, hair
      follicles, and sweat gland epithelial cells, while no positive staining was
      observed in fibroblasts. The mRNA expression levels of CAR in skin tissue
      sections in group C and group HS were respectively 0.157 +/- 0.027 and 0.773 +/-
      0.029. There was statistically significant difference between them (t = 3.052, P
      < 0.01). The protein expression levels of CAR in skin tissue sections in group C
      and group HS were respectively 0.23 +/- 0.09 and 0.89 +/- 0.14. There was
      statistically significant difference between them (t = 2.556, P < 0.05). (2) The
      apoptosis rates of KCs in group C and group HS were respectively (5.7 +/- 1.3)%
      and (7.4 +/- 1.7)% (t = 0.464, P > 0.05). The expression rates of CAR in KCs in
      group C and group HS were respectively (48 +/- 6)% and (80 +/- 8)%. There was
      statistically significant difference between them (t = 2.585, P < 0.05). (3) The
      contents of IGF-Iin culture supernatants in group C and 0.5, 1.0, 2.0, 4.0, 8.0,
      16.0 mg/L CAR groups were respectively (23.1 +/- 1.8), (22.5 +/- 2.1), (31.2 +/-
      2.5), (39.7 +/- 2.3), (61.8 +/- 3.5), (45.1 +/- 2.8), and (29.0 +/- 2.0) ug/L.
      There was statistically significant difference among 7 groups (F = 3.414, P <
      0.05). The contents of KGF in culture supernatants in group C and 0.5, 1.0, 2.0,
      4.0, 8.0, 16.0 mg/L CAR groups were respectively (131 +/- 9), (217 +/- 12), (355
      +/- 21), (563 +/- 21), (535 +/- 34), (292 +/- 20), and (245 +/- 10) ng/L. There
      was statistically significant difference among 7 groups (F = 5.063, P < 0.01).
      CONCLUSIONS: The expression of CAR in KCs would rise after HS. The optimum CAR
      concentration to increase IGF-I and KGF production in DETCs is low.

PMID- 24684989
TI  - [Influence of exogenous putrescine on the function of liver and apoptosis of
      liver cells in rats].
AB  - OBJECTIVE: To explore the influence of exogenous putrescine on the function of
      liver and apoptosis of liver cells in rats. METHODS: Ninety healthy clean SD rats
      were divided into control group (C, n = 10, intraperitoneally injected with 2 mL
      normal saline), low dosage putrescine group (LP, n = 40), and high dosage
      putrescine group (HP, n = 40) according to the random number table. Rats in the
      latter two groups were intraperitoneally injected with approximately 2 mL
      putrescine (2.5 or 5.0 g/L) with the dosage of 25 or 50 ug/g. Ten rats from group
      C at post injection hour (PIH) 24 and 10 rats from each of the latter two groups
      at PIH 24, 48, 72, 96 were sacrificed. Heart blood was obtained for determination
      of serum contents of ALT and AST. Liver was harvested for gross observation and
      histomorphological observation with HE staining. Apoptosis was shown with in situ
      end labeling, and apoptosis index (AI) was calculated. Data among the three
      groups and those at different time points within one group were processed with
      one-way analysis of variance or Welch test; LSD or Dunnett's T3 test was used for
      paired comparison; factorial design analysis of variance of two factors was
      applied for data between group LP and group HP. RESULTS: (1) No obvious
      abnormality was observed at gross observation of liver of rats in each group.
      Liver tissue of rats in group C was normal. Light edema was observed occasionally
      in liver of rats in groups LP and HP, but necrotic cells were not seen. (2)
      Content of ALT at PIH 24, 48, 96 and content of AST at PIH 72 and 96 in group LP
      were respectively (38 +/- 10), (45 +/- 6), (34 +/- 4), (207 +/- 18), (196 +/- 19)
      U/L, and content of ALT at PIH 72 and 96 and content of AST at PIH 24, 72, 96 in
      group HP were respectively (38 +/- 6), (48 +/- 5), (213 +/- 43), (209 +/- 40),
      (230 +/- 29) U/L. They were significantly higher than those of rats in group C
      [(29 +/- 5), (163 +/- 42) U/L, with P values all below 0.01]. There were
      statistically significant differences between group LP and group HP in the
      content of ALT at PIH 48, 72, 96 and content of AST at PIH 96 (with P values all
      below 0.05). Compared with that at PIH 24 of each group, content of ALT of rats
      in group LP at PIH 48 and that of rats in group HP at PIH 96, as well as content
      of AST of rats in group LP at PIH 48, 72, 96 and that of rats in group HP at PIH
      48 were significantly increased or decreased (with P values all below 0.05).
      Factorial analysis showed that the differences due to different concentration of
      putrescine on content of AST were statistically significant (F = 12.21, P =
      0.001), but not on content of ALT (F = 0.01, P = 0.974) between group LP and
      group HP. (3) AI values of rats in group LP at PIH 24, 48, 72 were respectively
      (5.69 +/- 0.38)%, (13.80 +/- 1.66)%, (11.56 +/- 1.74)%, and AI values of rats in
      group HP at PIH 72 and 96 were respectively (10.29 +/- 1.43)%, (15.29 +/- 1.41)%.
      They were all obviously higher than AI value of control group at PIH 24 [(3.50 +/
      0.30)%, with P values all below 0.01]. There were statistically significant
      differences between group LP and group HP in AI value at PIH 24, 48, 96 (with P
      values all below 0.05). Compared with that at PIH 24 of each group, AI value of
      rats in groups LP and HP at PIH 48, 72, 96 were significantly increased or
      decreased (with P values all below 0.05). Factorial analysis showed that the
      differences in the influence of concentration of putrescine and stimulation time
      on AI value were statistically significant (with F values respectively 22.95 and
      130.44, P values all below 0.01). CONCLUSIONS: Intraperitoneal injection of
      exogenous putrescine in the dosage of 25 or 50 ug/g could lead to certain degree
      of functional damage of liver and apoptosis of liver cells of rat. The higher the
      dosage and the longer the stimulation time, the more obvious the damage and
      apoptosis would be.

PMID- 24684990
TI  - [Effects of different position during high frequency oscillatory ventilation on
      oxygenation and hemodynamics of dogs with severe smoke inhalation injury].
AB  - OBJECTIVE: To study the effects of high frequency oscillatory ventilation (HFOV)
      with different position on oxygenation and hemodynamics of dogs with severe smoke
      inhalation injury. METHODS: After being treated with conventional mechanical
      ventilation, 12 dogs were inflicted with severe smoke inhalation injury and
      treated by HFOV for 30 min. They were divided into HFOV+prone positioning (PP)
      group and HFOV+supine positioning (SP) group according to the random number
      table, with 6 dogs in each group. They received HFOV with corresponding position
      for 8 hours respectively. RESULTS: of blood gas analysis (pH, PaO2 and PaCO2
      levels), oxygen index (OI) and hemodynamic parameters [heart rate, mean arterial
      pressure (MAP), and cardiac output (CO)] were recorded or calculated before
      injury, immediately after injury, and at post ventilation hour (PVH) 2, 4, 6, 8.
      Data were processed with analysis of variance of repeated measurement, and LSD- t
      test. RESULTS: (1) At PVH 8, pH value of dogs in group HFOV+PP was significantly
      higher than that in group HFOV+SP (t = 3.0571, P < 0.05). Compared with those
      observed immediately after injury, except for group HFOV+SP at PVH 2 and 4 (with
      t values respectively 2.066 5 and 1.440 7, P values all above 0.05), the pH
      values in both groups at other treatment time points were decreased (with t
      values from 2.449 5 to 3.985 3, P < 0.05 or P < 0.01). At PVH 2, 4, 8, the PaO2
      levels in group HFOV+PP [(131 +/- 26), (150 +/- 40), (112 +/- 30) mmHg, 1 mmHg =
      0.133 kPa] were higher than those in group HFOV+SP [(81 +/- 15), (96 +/- 5), (83
      +/- 6) mmHg, with t values from 2.366 4 to 4.083 5, P < 0.05 or P < 0.01]. The
      PaO2 levels in both groups from PVH 2 to PVH 8 were increased, compared with
      those observed immediately after injury [(55 +/- 15) mmHg in group HFOV+SP and
      (48 +/- 11) mmHg in group HFOV+PP, with t values from 2.473 6 to 7.2310, P < 0.05
      or P < 0.01]. No statistically significant differences were observed in PaCO2
      level at each time point between two groups (with t values from 0.661 0 to 2.141
      9, P values all above 0.05). No statistically significant differences were
      observed in PaCO2 levels from PVH 2 to PVH 8 compared with those observed
      immediately after injury in both groups (with t values from 0.126 2 to 1.768 3, P
      values all above 0.05). (2) The OI values in group HFOV+SP were significantly
      higher than those in group HFOV+PP from PVH 2 to PVH 8 (with t values from 3.091
      9 to 3.791 6, P < 0.05 or P < 0.01). The OI values in both groups from PVH 2 to
      PVH 8 were significantly decreased, compared with those observed immediately
      after injury (with t values from 2.702 0 to 5.969 3, P < 0.05 or P < 0.01). (3)
      At PVH 6 and PVH 8, heart rate in group HFOV+PP was significantly higher than
      that in group HFOV+SP (with t values respectively 4.255 9 and 4.765 9, P values
      both below 0.01). Compared with that observed immediately after injury, heart
      rate in group HFOV+PP was significantly decreased (with t values from 3.006 2 to
      5.135 5, P < 0.05 or P < 0.01) except for PVH 2 (t = 1.938 2, P > 0.05). However,
      there was no statistical significant difference at each treatment time point in
      group HFOV+PP (with t values from 0.786 5 to 1.525 8, P values all above 0.05).
      There was no statistically significant difference in MAP between two groups at
      each time point (with t values from 0.045 8 to 1.783 4, P values all above 0.05).
      Compared with that observed immediately after injury, MAP in group HFOV+SP was
      significantly decreased at PVH 8 (t = 2.368 3, P < 0.05); MAP in group HFOV+PP
      was significantly decreased at PVH 2 (t = 3.580 1, P < 0.01). At PVH 2 and 4, the
      CO values in group HFOV+SP were significantly higher than those in group HFOV+PP
      (with t values respectively 2.310 3 and 4.526 5, P values both below 0.01).
      Except for group HFOV+SP at PVH 2 (t = 1.294 1, P > 0.05), CO values at other
      treatment time points in both groups were significantly lower than that observed
      immediately after injury (with t values from 2.247 0 to 4.067 8, P < 0.05 or P <
      0.01). CONCLUSIONS: HFOV+ PP can improve oxygenation with no obvious CO2
      retention or adverse effect on hemodynamic parameters of dogs with severe smoke
      inhalation injury. Therefore, it is recommended for clinical application.

PMID- 24684991
TI  - [Advances in the research of rheological behavior of platelets and its regulation
      after burn].
AB  - Microcirculatory dysfunction of local wounds and distant tissues after burns
      results in ischemia and hypoxia of tissues and organs, thus affecting the course
      and prognosis of burns. Platelet is an important component of blood, and the
      changes in its rheological behavior influence the blood flow in the
      microcirculation, as well as the microvascular structure and function. The
      abnormality of platelet rheological behavior plays an important role in the
      occurrence and development of microcirculatory dysfunction after burn. Changes in
      rheological behavior of platelets are due to changes in platelet morphology,
      adhesion, aggregation, shrinkage functions, and release reaction. Investigation
      of platelet rheological behavior and its regulation after burn may be of
      significant implication in the analysis of patient's condition and instruction
      for treatment. This article reviews the changes in platelet rheological behavior
      and its regulation after burn in the aspects of morphology, adhesion,
      aggregation, shrinkage functions, and release reaction. 

PMID- 24684992
TI  - Evaluation of in vivo antitrypanosomal activity of crude extracts of Artemisia
      abyssinica against aTrypanosoma congolense isolate.
AB  - BACKGROUND: African trypanosomiasis is a major disease of economic and public
      health importance affecting agricultural and human development. The search for
      alternative compounds against African trypanosomiasis is justified by various
      limitations of existing chemotherapeutic agents. This study was aimed at
      screening the hydromethanolic and dichloromethane (DCM) crude extracts of aerial
      parts of Artemisia abyssinica for in vivo antitrypanosomal activity against
      Trypanosoma congolense isolate in mice. METHODS: The aerial parts of the plant
      were extracted by maceration technique using dichloromethane and 80% methanol to
      obtain the corresponding crude extracts. The plant extracts at doses of 100, 200
      and 400 mg/kg body weight were administered intraperitoneally daily for 7 days to
      mice infected with Trypanosoma congolense. Diminazene aceturate and distilled
      water were used as positive and as negative controls respectively. The level of
      parasitaemia, body weight, packed cell volume, differential leukocyte counts and
      mean survival period were monitored. RESULTS: The study showed that the DCM
      extract at 200 and 400 mg/kg, and the hydromethanolic extract at 400 mg/kg
      reduced parasitaemia (p < 0.05), ameliorated anaemia (p < 0.05), prevented body
      weight loss (p < 0.05) and resulted in significant increase in neutrophil levels
      (p < 0.05) and marked decrease in lymphocyte levels (p < 0.05) compared to the
      negative control. CONCLUSIONS: This study established that aerial parts of A.
      abyssinica have antitrypanosomal potential and can be considered a potential
      source of new drugs for the treatment of tropical diseases caused by
      trypanosomes.

PMID- 24684994
TI  - Cardiovascular implantable electronic device infective endocarditis.

PMID- 24684993
TI  - Balloon valvuloplasty after Transcatheter Aortic Valve Implantation (TAVI):
      always safe?

PMID- 24684995
TI  - Contrast-enhancing right atrial thrombus in cancer patient.

PMID- 24684996
TI  - Cardiac imaging training in the United Kingdom - rise of the machines.

PMID- 24684997
TI  - Determinants of exercise-induced pulmonary arterial hypertension in systemic
      sclerosis.
AB  - BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPH) in systemic
      sclerosis (SSc) has already been observed but its determinants remain unclear.
      The aim of this study was to determine the incidence and the determinants of EIPH
      in SSc. METHODS AND RESULTS: We prospectively enrolled 63 patients with SSc (age
      54+/-3years, 76% female) followed in CHU Sart-Tilman in Liege. All patients
      underwent graded semi-supine exercise echocardiography. Systolic pulmonary
      arterial pressure (sPAP) was derived from the peak velocity of the tricuspid
      regurgitation jet and adding the estimation of right atrial pressure, both at
      rest and during exercise. Resting pulmonary arterial hypertension (PH) was
      defined as sPAP > 35 mmHg and EIPH as sPAP > 50 mmHg during exercise. The
      following formulas were used: mean PAP (mPAP) = 0.61 * sPAP + 2, left atrial
      pressure (LAP)=1.9+1.24 * left ventricular (LV) E/e' and pulmonary vascular
      resistance (PVR)=(mPAP-LAP)/LV cardiac output (CO) and slope of mPAP-LVCO
      relationship=changes in mPAP/changes in LVCO. Resting PH was present in 3
      patients (7%) and 21 patients developed EIPH (47%). Patients with EIPH had higher
      resting LAP (10.3 +/- 2.2 versus 8.8 +/- 2.3 mmHg; p = 0.03), resting PVR (2.6 +/
      0.8 vs. 1.4 +/- 1.1 Woods units; p=0.004), exercise LAP (13.3 +/- 2.3 vs. 9 +/-
      1.7 mmHg; p < 0.0001), exercise PVR (3.6 +/- 0.7 vs. 2.1 +/- 0.9 Woods units; p =
      0.02) and slope of mPAP-LVCO (5.8 +/- 2.4 vs. 2.9 +/- 2.1 mmHg/L/min; p <
      0.0001). After adjustment for age and gender, exercise LAP (beta=3.1 +/- 0.8;
      p=0.001) and exercise PVR (beta=7.9 +/- 1.7; p=0.0001) were independent
      determinants of exercise sPAP. CONCLUSION: EIPH is frequent in SSc patients and
      is mainly related to both increased exercise LV filling pressure and exercise
      PVR.

PMID- 24684998
TI  - The interventricular septum in pulmonary hypertension does not show features of
      right ventricular failure.

PMID- 24684999
TI  - Cardiac autonomic nervous activity in adults with coarctation of the aorta late
      after repair.

PMID- 24685000
TI  - Relation of socioeconomic status to hypertension occurrence.

PMID- 24685001
TI  - Direct implantation versus platelet-rich fibrin-embedded adipose-derived
      mesenchymal stem cells in treating rat acute myocardial infarction.
AB  - BACKGROUND: This study tested whether adipose-derived mesenchymal stem cells
      (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct
      ADMSC implantation in improving left ventricular (LV) performance and reducing LV
      remodeling in a rat acute myocardial infarction (AMI) model of left anterior
      descending coronary artery (LAD) ligation. METHODS: Twenty-eight male adult
      Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI
      only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded
      autologous ADMSC) were sacrificed on day 42 after AMI. RESULTS: LV systolic and
      diastolic dimensions and volumes, and infarct/fibrotic areas were highest in
      group 2, lowest in group 1 and significantly higher in group 3 than in group 4,
      whereas LV performance and LV fractional shortening exhibited a reversed pattern
      (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1beta, MMP
      9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-beta), and
      pressure-overload biomarkers (BNP, MHC-beta) displayed a pattern similar to that
      of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and
      anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV
      performance among the four groups (all p<0.05). Angiogenesis biomarkers at
      protein (CXCR4, SDF-1alpha, VEGF), cellular (CD31+, CXCR4+, SDF-1alpha+), and
      immunohistochemical (small vessels) levels, and cardiac stem cell markers (C
      kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1,
      and significantly higher in group 3 than in group 2 (all p<0.005). CONCLUSION:
      PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV
      function and attenuating LV remodeling.

PMID- 24685004
TI  - Relationship of left ventricular hypertrophy, age, and renal artery stenosis.

PMID- 24685003
TI  - Changes in cerebrospinal fluid and blood plasma levels of IGF-II and its binding
      proteins in Alzheimer's disease: an observational study.
AB  - BACKGROUND: The Insulin-like Growth Factor (IGF)-related system is implicated in
      neuroregeneration and cell repair, as well as regulating lifespan. IGF-II, one
      component of this system, has also been found to affect memory functions in a rat
      model. In this study we explored changes in the IGF-related system in patients
      with Alzheimer's disease (AD), including changes in IGF-II levels. METHODS: We
      measured blood plasma and cerebrospinal fluid (CSF) levels of IGF-I, IGF-II,
      IGFBP-2 and IGFBP-3 in 72 healthy controls and 92 patients with AD. RESULTS: We
      found significantly lower blood plasma levels of IGF-II and IGFBP-3 in patients
      with AD, compared with controls. The levels of IGF-II and IGFBP-2 were
      significantly elevated in the CSF from patients with AD. We also found
      correlations between established CSF biomarkers for AD (tau and P-tau) and
      components of the IGF system. CONCLUSIONS: CSF and blood plasma levels of IGF-II
      and some of its binding proteins are changed in patients with AD. Further
      investigation into this area may unravel important clues to the nature of this
      disease.

PMID- 24685002
TI  - Long noncoding RNAs, emerging players in muscle differentiation and disease.
AB  - The vast majority of the mammalian genome is transcribed giving rise to many
      different types of noncoding RNAs. Among them, long noncoding RNAs are the most
      numerous and functionally versatile class. Indeed, the lncRNA repertoire might be
      as rich as the proteome. LncRNAs have emerged as key regulators of gene
      expression at multiple levels. They play important roles in the regulation of
      development, differentiation and maintenance of cell identity and they also
      contribute to disease. In this review, we present recent advances in the biology
      of lncRNAs in muscle development and differentiation. We will also discuss the
      contribution of lncRNAs to muscle disease with a particular focus on Duchenne and
      facioscapulohumeral muscular dystrophies. 

PMID- 24685007
TI  - Efficacy and safety of a new fully covered self-expandable non-foreshortening
      metal esophageal stent.
AB  - BACKGROUND: Fully covered esophageal self-expandable metal stents (SEMSs) are
      potentially removable but can be associated with high migration rates. For
      precise positioning, non-foreshortening SEMSs are preferred. Recently, a new
      fully covered non-foreshortening SEMS with anti-migration features was
      introduced. OBJECTIVE: To evaluate the efficacy and safety of this new esophageal
      SEMS. DESIGN: Retrospective study. SETTING: Single, tertiary-care center.
      PATIENTS: Consecutive patients with malignant and benign strictures with
      dysphagia grade of >=3 and patients with fistulas/leaks were studied.
      INTERVENTIONS: Stent placement and removal. MAIN OUTCOME MEASUREMENTS: Technical
      success in stent deployment/removal, efficacy in relieving dysphagia and sealing
      fistulas/leaks, and adverse events. RESULTS: Forty-three stents were placed in 35
      patients (mean [+/- standard deviation] age 65 +/- 11 years; 31 male), 24 for
      malignant and 11 for benign (5 strictures, 6 leaks) indications. Technical
      success in precise SEMS placement was 100%. The after-stent dysphagia grade
      improved significantly (at 1 week: 1.5 +/- 0.7; at 4 weeks: 1.2 +/- 0.4;
      baseline: 3.8 +/- 0.4; P < .0001). Twenty stents were removed for clinical
      indications, with technical success of 100%. All leaks sealed after SEMS
      placement and did not recur after stent removal. All benign strictures recurred
      after stent removal. Adverse events included migration (14%), chest pain (11%),
      and dysphagia from tissue hyperplasia (6%). There was no stent-related mortality.
      LIMITATIONS: Nonrandomized, single-center study. CONCLUSION: The new esophageal
      SEMS was effective in relieving malignant dysphagia, allowed for precise
      placement, and was easily removable. It was effective in treating benign
      esophageal fistulas and leaks. Stent-related adverse events were acceptable.

PMID- 24685006
TI  - Effects of amlodipine and other classes of antihypertensive drugs on long-term
      blood pressure variability: evidence from randomized controlled trials.
AB  - Blood pressure (BP) is monitored and managed to prevent cardiovascular
      complications of hypertension, but BP variability (BPV) has not been sufficiently
      studied. This analysis assessed whether patients receiving amlodipine vs other
      antihypertensive agents had lower BPV after >=12 weeks of treatment. Studies were
      included if individual subject data were available, had >=1 active comparator,
      and treatment duration was >=12 weeks. BPV was assessed using standard deviation
      (SD) and coefficient of variation (CV) of systolic BP across visits from 12
      weeks. Individual trial and meta-analyses were performed for SD- and CV-based
      methodology. Five studies (47,558 BPV-evaluable patients) were included. Patient
      characteristics were largely consistent across the studies, but BP measurements
      varied from ~4 months to ~6 years. BPV with amlodipine was significantly (P <
      .0001) lower vs atenolol and lisinopril; significantly (P < .0001) lower than
      enalapril in one study and numerically, but not significantly lower in another;
      and similar to chlorthalidone and losartan. Meta-analysis revealed a treatment
      difference (standard error) for amlodipine vs all active comparators of -1.23
      (0.46; P = .008) mm Hg using SD and -0.86 (0.31; P = .005) using CV. These
      findings suggest that amlodipine is effective for minimizing BPV. Future studies
      need to confirm a causal link between BPV and cerebrovascular/cardiovascular
      outcomes. 

PMID- 24685005
TI  - Detection of early diastolic alterations by tissue Doppler imaging in untreated
      childhood-onset essential hypertension.
AB  - The aim of the study was to determine the presence of preclinical diastolic
      dysfunction in hypertensive children relative to normotensive children by Tissue
      Doppler Imaging (TDI). We prospectively enrolled children with untreated
      essential hypertension in absence of any other disease and a matched healthy
      control group with normal blood pressure (BP); both groups confirmed by clinic BP
      and a 24-hour ambulatory BP monitoring. Echocardiographic diastolic parameters
      were determined using spectral transmitral inflow Doppler, flow propagation
      velocity, TDI, and systolic parameters were determined via midwall shortening
      fraction and ejection fraction. A total of 80 multiethnic children were
      prospectively enrolled for the study: 46 hypertensive (median age, 13 years; 72%
      males) and 34 control (median age, 14 years; 65% males). The only
      echocardiography parameters that had a statistically significant change compared
      with the control children, were regional mitral Ea, Aa, and the E/Ea ratio by
      TDI. In comparison with controls, hypertensive children had lower Ea and Aa
      velocities of anterior and posterior walls and higher lateral wall E/Ea ratio.
      The decrease in posterior wall Ea and Aa remained significant after adjustment
      for gender, age, body mass index, ethnicity, and left ventricular hypertrophy on
      multivariate analysis. The lateral and septal wall E/Ea ratios correlated
      significantly with fasting serum insulin levels on similar multivariate analysis.
      Decreased regional TDI velocities were seen with preserved left ventricular
      systolic function even when other measures of diastolic dysfunction remained
      unchanged in untreated hypertensive children. Hypertension and serum insulin
      levels had strong associations with preclinical diastolic alterations in
      children. 

PMID- 24685008
TI  - Point-of-care testing for celiac disease has a low sensitivity in endoscopy.
AB  - BACKGROUND: Celiac disease (CD) is a common but underdiagnosed condition. A rapid
      point-of-care test (POCT) could reduce lead times and missed diagnoses.
      OBJECTIVE: To assess the utility of an immunoglobulin (Ig) A tissue
      transglutaminase (TTG) antibody POCT in an endoscopic setting. DESIGN:
      Prospective observational study. SETTING: A single UK university hospital.
      PATIENTS: Patients presenting with suspected CD, known CD, and routine endoscopy
      for upper GI symptoms. INTERVENTIONS: All patients were tested with POCT, serum
      TTG, endomysial antibody (EMA), and upper GI endoscopy with duodenal biopsies at
      the same visit. MAIN OUTCOME MEASUREMENTS: Comparison was made with histology in
      all cases, with villous atrophy regarded as diagnostic of CD. RESULTS: A total of
      576 patients (63.5% female, mean [+/- standard deviation] age 49.7 years [+/-
      17.6 years]) were recruited. A total of 523 patients had no prior diagnosis of
      CD, and 53 patients had known CD coming for reassessment. A total of 117 patients
      were newly diagnosed with CD, and 82 were positively identified by the POCT.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were 70.1%, 96.6%, 85.4%, and 91.8%, respectively. In comparison, TTG and
      EMA both performed significantly better than the POCT. Sensitivity and
      specificity of TTG were 91.0% and 83.5%, respectively, and EMA were 83.8% and
      97.5%, respectively. Of patients with known CD coming for reassessment, 26 had
      villous atrophy, and POCT results were positive in 16 (61.5%). There was poor
      agreement between POCT and standard serology. LIMITATIONS: High pre-test
      probability of CD. CONCLUSION: The performance of this POCT was disappointing
      compared with standard serology and cannot at present be recommended within the
      context of an endoscopy unit.

PMID- 24685009
TI  - Multiple endocrine disorders associated with adrenomyeloneuropathy and a novel
      mutation of the ABCD1 gene.
AB  - INTRODUCTION: X-linked adrenomyeloneuropathy (X-AMN) is a genetic disorder that
      primarily affects the adrenal cortex and the nervous system. The disease shows a
      wide range of phenotypic expression, age of onset, and rate of progression.
      PATIENT DESCRIPTION: We present a thalassemic 23-year-old man with X-AMN and
      multiple endocrine disorders. At age 2 years, he was diagnosed with thalassaemia
      intermedia, and he was receiving occasional blood transfusions and maintaining an
      adequate hemoglobin level without signs of extramedullar hematopoiesis or
      hemosiderosis. During adolescence, he was diagnosed with growth hormone
      deficiency, primary hypothyroidism, and primary adrenal insufficiency. In his
      early 20s he demonstrated progressive tetraparesis, and the diagnosis of X-AMN
      was confirmed by DNA analysis of the ABCD1 gene. CONCLUSION: This patient expands
      the phenotype X-AMN by adding growth hormone deficiency and hypothyroidism.

PMID- 24685010
TI  - Leukodystrophy presenting as acute-onset polyradiculoneuropathy.
AB  - BACKGROUND: Sulfatides, the most abundant glycosphingolipids, are a major
      component of myelin. They are degraded by the combined action of sphingolipid
      activator protein and arylsulfatase A. Deficiency of either of these entities
      causes metachromatic leukodystrophy (MLD). On the basis of age of onset, this
      entity is divided into late infantile, juvenile, and adult subtypes. Late
      infantile form, the commonest subtype, can exhibit peripheral neuropathy as the
      initial manifestation. The other two forms usually manifest peripheral neuropathy
      later in the disease course. PATIENT: A 1.5-year-old girl with preexisting
      isolated motor delay presented with acute-onset ascending flaccid quadriparesis,
      ptosis, and respiratory failure. Ptosis and respiratory failure responded
      completely to intravenous immunoglobulin, whereas quadriparesis showed minimal
      improvement. Nerve biopsy revealed metachromatic granules with demyelination, and
      serum arylsulfatase A levels were undetectable. CONCLUSION: The severity and
      nature of the disease coupled with the response to immunotherapy makes this case
      unusual. This child may represent either an atypical presentation of MLD with
      coincidental response to immunotherapy or an episode of immune mediated
      neuropathy in an individual with already diseased nerves due to MLD.

PMID- 24685011
TI  - Absence of Wolbachia endobacteria in the human parasitic nematode Dracunculus
      medinensis and two related Dracunculus species infecting wildlife.
AB  - BACKGROUND: Wolbachia endosymbionts are a proven target for control of human
      disease caused by filarial nematodes. However, little is known about the
      occurrence of Wolbachia in taxa closely related to the superfamily Filarioidea.
      Our study addressed the status of Wolbachia presence in members of the
      superfamily Dracunculoidea by screening the human parasite Dracunculus medinensis
      and related species from wildlife for Wolbachia. FINDINGS: D. medinensis, D.
      lutrae and D. insignis specimens were all negative for Wolbachia colonization by
      PCR screening for the Wolbachia ftsZ, 16S rRNA and Wolbachia surface protein
      (wsp) sequences. The quality and purity of the DNA preparations was confirmed by
      amplification of nematode 18S rRNA and cytochrome c oxidase subunit I sequences.
      Furthermore, Wolbachia endobacteria were not detected by whole mount fluorescence
      staining, or by immunohistochemistry using a Wolbachia-specific antiserum. In
      contrast, positive control Brugia malayi worms were shown to harbour Wolbachia by
      PCR, fluorescence staining and immunohistochemistry. CONCLUSIONS: Three examined
      species of Dracunculus showed no evidence of Wolbachia endobacteria. This
      supports that members of the superfamily Dracunculoidea are free of Wolbachia.
      Within the order Spirurida, these endosymbionts appear restricted to the
      Filarioidea.

PMID- 24685012
TI  - A case-cohort study with propensity score matching to evaluate the effects of
      mannitol on venous thromboembolism.
AB  - Mannitol has been shown to damage endothelial cells and activate coagulation
      pathways leading to intravascular thrombosis. Dehydration and hemagglutination
      have also been associated with mannitol use, although the risk of clinically
      evident venous thromboembolism (VTE) disease is not well-defined. The aim of this
      study was to compare the risk of VTE in critically ill neurological patients who
      received mannitol compared to only hypertonic saline. A case-cohort study design
      with propensity score matching was used to evaluate the risk of VTE among
      patients who received mannitol compared to those who received hypertonic saline
      alone. The odds of thrombosis were evaluated by the Cochran-Mantel-Haenszel
      method and conditional logistic regression was used to adjust for year of
      treatment. Ninety-one of 330 patients (27.6%; 95% confidence interval [CI] 23
      33%) developed a VTE; however, the yearly proportion remained unchanged over the
      8 year study period. Cumulative use of mannitol declined and use of hypertonic
      saline increased significantly. The odds of thrombosis for those exposed to
      mannitol compared to hypertonic saline alone was 1.11 (95% CI 0.65-1.73; p=0.75).
      This remained insignificant after adjusting for year of injury. In conclusion,
      despite a significant change in the pattern of osmotic therapy used at our
      institution, the proportion of patients with VTE remained unchanged. We found no
      evidence that mannitol use was associated with VTE compared to hypertonic saline
      alone.

PMID- 24685013
TI  - Resilience at the border: traditional botanical knowledge among Macedonians and
      Albanians living in Gollobordo, Eastern Albania.
AB  - BACKGROUND: Ethnobotany in South-Eastern Europe is gaining the interest of
      several scholars and stakeholders, since it is increasingly considered a key
      point for the re-evaluation of local bio-cultural heritage. The region of
      Gollobordo, located in Eastern Albania and bordering the Republic of Macedonia,
      is of particular interest for conducting ethnobiological studies, since it
      remained relatively isolated for the larger part of the 20th Century and is
      traditionally inhabited by a majority of ethnic Macedonians and a minority of
      Albanians (nowadays both sharing the Muslim faith). METHODS: An ethnobotanical
      survey focused on local food, medicinal, and veterinary plant uses was conducted
      with 58 participants using open and semi-structured interviews and via
      participant observation. RESULTS: We recorded and identified 115 taxa of vascular
      plants, which are locally used for food, medicinal, and veterinary purposes
      (representing 268 total plant reports). The Macedonian Traditional Ecological
      Knowledge (TEK) was greater than the Albanian TEK, especially in the herbal and
      ritual domains. This phenomenon may be linked to the long socio-cultural and
      linguistic isolation of this group during the time when the borders between
      Albania and the former Yugoslavia were completely closed. Moreover, the unusual
      current food utilisation of cooked potatoes leaves, still in use nowadays among
      Macedonians, could represent the side effect of an extreme adaptation that locals
      underwent over the past century when the introduction of the potato crop made new
      strategies available for establishing stable settlements around the highest
      pastures. Additionally, the difference in use of Helichrysum plicatum, which is
      popular in the local Macedonian folk medicine but absent among Albanians,
      confirms the particular significance of this taxon as it relates to the yellow
      colour of its flowers in South Slavic folklore. CONCLUSION: Botanical studies
      with an ethnographic approach are crucial for understanding patterns of use of
      plants within given cultures. Importantly, such studies can also allow for
      analysis of the dynamics of change in these TEK patterns over the time. The
      results of this study may be important as baseline data set to be used in rural
      development programs in Gollobordo, aimed at fostering community-based strategies
      of management of natural resources.

PMID- 24685015
TI  - Richness and diversity of helminth species in eels from a hypersaline coastal
      lagoon, Mar Menor, south-east Spain.
AB  - The composition and diversity of parasite communities and intestinal components,
      as well as infra-community structure, were assessed in eels Anguilla anguilla,
      from Mar Menor, a permanent Mediterranean hypersaline coastal lagoon. Data were
      used to determine whether this helminth community differs in composition and
      structure from that of eels in lagoons with lower salinity regimes and higher
      freshwater inputs. A total prevalence of 93% was detected. Specifically,
      parasites were identified as Deropristis inflata, Bucephalus anguillae,
      Contracaecum sp., Anguillicoloides crassus and two plerocercoid larvae belonging
      to the order Proteocephalidae, the marine species representing 91% of the
      isolated helminths. In the total community, digenetic trematodes were the
      dominant group of helminths, and D. inflata, an eel specialist, dominated both
      the component community and the infra-community. Richness and diversity were low
      but similar to those reported in other saline lagoons, and maximum species per
      eel did not exceed four. At the infra-community level, higher abundance than in
      other brackish or marine Mediterranean environments was detected. The findings
      provide further evidence of the similarity in composition and structure of
      helminth communities in eels from various Mediterranean coastal lagoons.
      Moreover, salinity-dependent specificities are well supported and reflect the
      life history of individual eels. 

PMID- 24685014
TI  - Does specific interventional risk scoring better predict mortality than
      comorbidity in nonagenerians undergoing coronary angioplasty?
AB  - BACKGROUND: Preliminary study to assess the risk profile and outcomes of patients
      aged over 90years at the time of percutaneous coronary intervention. METHODS: A
      database search was performed to identify patients 90years or over at the time of
      percutaneous coronary intervention. Risk profile scores (Charlson Comorbidity
      Index, SYNTAX, Logistic clinical SYNTAX, New York PTCA score and frailty indices)
      were evaluated on 24 consecutive patients in order to determine the best
      predictor for survival. Between both groups (survivors and non-survivors)
      unpaired Student's t-test was used to determine statistical significance.
      RESULTS: The New York PTCA score was significantly higher in those patients that
      died in hospital (n=5) when compared to those who survived to discharge (n=19)
      (NY PTCA score of 20.9+/-5.4 vs. 4.5+/-0.8, p<0.001) and this was also seen with
      mortality at 12months. The level of co-morbidity (Charlson index) was similar in
      patients who died in hospital (n=5) compared with those who survived to discharge
      (n=19, Charlson comorbidity index of 3.4+/-0.7 vs.3.9+/-0.6, p=0.70). This trend
      was also observed at 1year. The average level of frailty (by the CSHA Clinical
      Frailty Scale), SYNTAX score and logistic clinical SYNTAX were not significantly
      different between the two groups both at discharge and at 12months. Choosing an
      arbitrary New York PTCA score of 9%, nearly two thirds of patients above this
      level died, whereas no patient below this level of risk died in hospital.
      CONCLUSION: This small observational study found that nonagenarians who underwent
      PCI had relatively low comorbidity and SYNTAX scores. The specific coronary
      intervention (New York PTCA) risk score appears to have more predictive power in
      this small group of patients than the other three scores. Crucially, the factors
      that determine risk by New York PTCA score - haemodynamic instability, shock,
      pulmonary oedema, renal failure, etc. - are commonly encompassed by an "end-of
      bed" assessment of the patient and these patients that pass this test ought not
      to be denied PCI on the basis of their advanced years.

PMID- 24685016
TI  - Reconceptualising failure to rescue in midwifery: a concept analysis.
AB  - AIM: to reconceptualise the concept of failure to rescue, distinguishing it from
      its current scientific usage as a surveillance strategy to recognise physiologic
      decline. BACKGROUND: failure to rescue has been consistently defined as a failure
      to save a patient's life after development of complications. The term, however,
      carries a richer connotation when viewed within a midwifery context. Midwives
      have historically believed themselves to be the vanguards of normal, physiologic
      processes, including birth. This philosophy mandates careful consideration of
      what it means to promote normal birth and the consequences of failure to rescue
      women from processes which challenge that outcome. DATA SOURCES: the Medline,
      CINAHL, PsycINFO, PubMED, Web of Science and Google Scholar databases were
      searched from the period of 1992-2014 using the key terms of concept analysis,
      failure-to-rescue, childbirth, midwifery outcomes, obstetrical outcomes,
      suboptimal care, and patient outcomes. English language reports were used
      exclusively. The search yielded 45 articles which were reviewed in this paper.
      REVIEW METHOD: a critical analysis of the published literature was undertaken as
      a means of determining the adequacy of the concept for midwifery practice and to
      detail how it relates to other concepts important in development of a conceptual
      framework promoting normal birth processes. FINDINGS: failure to rescue within
      the context of the midwifery model of care requires robust attention to a
      midwifery managed setting and surveillance based on a caring presence, patient
      protection, and midwifery partnership with patient. CONCLUSION: clarifying the
      definition of failure to rescue in childbirth and defining its attributes can
      help inform midwifery providers throughout the world of the ethical importance of
      considering failure to rescue in clinical practice. Relevance to midwifery care
      mandates use of failure to rescue as both a process and outcome measure.

PMID- 24685017
TI  - Decreased nerve fibers in the oviduct isthmus of women with endometriosis.
AB  - Oviduct tubal motility is thought to be controlled by hormones and nerves and has
      been associated with endometriosis. However, it is still not known whether the
      fallopian tubes in women with endometriosis demonstrate an abnormal distribution
      of nerve fibers. The objective of this study was to determine the distribution of
      nerve fibers in the oviduct isthmus in women with and without endometriosis.
      Histological sections of the oviduct isthmus tissues were obtained from women
      undergoing hysterectomy for endometriosis (n=24) and other benign gynecologic
      diseases (n=24). The tissues were immunohistochemically stained for protein gene
      product (PGP) 9.5, substance P (SP), neuropeptide Y (NPY), and vasoactive
      intestinal peptide (VIP) to reveal all nerve fibers, sensory nerve fibers and
      sympathetic and parasympathetic nerve fibers. Nerve fibers stained with PGP9.5,
      VIP and NPY in the oviduct isthmus were all significantly decreased in women with
      endometriosis as compared with women without endometriosis (P<0.05). In women
      with endometriosis, reduced nerve fibers stained with PGP9.5 and SP in the
      serosal layer, NPY in the muscular and mucosal layers, and VIP in the mucosal
      layer of the oviduct isthmus were all associated with the severity of the disease
      (P<0.05). These results suggest that decreased nerve fibers in the oviduct
      isthmus in women with endometriosis in comparison to women without may imply a
      role in the pathogenesis of endometriosis. 

PMID- 24685018
TI  - Peroxisome determination in optical microscopy: a useful tool derived by a
      simplification of an old ultrastructural technique.
AB  - Peroxisomes are able to respond to changes in the cellular environment by
      adapting their number, morphology and metabolic functions. Recently interest in
      peroxisomes and their possible roles in physiological and pathological processes
      have significantly increased. In order to identify peroxisomes, several
      cytochemical techniques have been developed that require fairly complex
      procedures or are too expensive to be used for screening. In this paper we show
      that it is possible to label peroxisomes in several cell lines and in tissues by
      a simple and cheap technique based on 3,3'-diaminobenzidine (DAB) reactivity. The
      number of peroxisomes detected with this technique in each cell line was similar
      to that shown by catalase immunoreaction. The technique appears specific because
      it was able to detect increased number of peroxisomes after treatment with the
      specific PPARgamma antagonist G3335. Gomori's technique for acid phosphatase
      activity was used to demonstrate that the DAB positive organelles were not
      lysosomes. The DAB technique has also been applied to transmission electron
      microscopy, where it labels round structures that are identified as peroxisomes
      on the basis of morphology, size and localization. The DAB technique has proved
      to be specific, simple, fast and cheap, which make it ideal to screen possible
      peroxisome changes in physiological and pathological conditions. 

PMID- 24685019
TI  - Dural dissection cyst: a more accurate term for extradural meningeal cyst.
AB  - AIMS: Spinal extradural meningeal cyst (EMC) aetiology remains unclear. Based on
      our in-depth analysis of EMC clinical characters, we propose the alternative term
      'dural dissection cyst' (DDC), which is more consistent with its aetiology and
      pathological manifestations. METHODS: We examined the clinical, imaging and
      operative findings of four patients with spinal EMC (type I A) and analysed the
      aetiology and treatment of the cyst. RESULTS: Spinal DDC was observed between T10
      and L3 in our series. Patients presented with low back pain, lower extremity
      numbness and weakness, and segmental muscle atrophy. Small clefts were found on
      the inner wall of all cysts. Microscopic suture of the cleft successfully
      improved patient's symptoms and neurological deficits. CONCLUSIONS: Spinal EMC
      (type I A) is characterized by dural dissection, so the term DDC can best reflect
      its aetiology. Because it is a dissection cyst, the most reasonable treatment is
      to suture the fistula.

PMID- 24685020
TI  - A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds
      powder in menopausal women.
AB  - BACKGROUND: The risk of cardiovascular diseases (CVD) is increased tremendously
      among menopausal women, and there is an increasing demand for alternative
      therapies for managing factors like dyslipidemia that contribute to CVD
      development. METHODS: In this study, Nigella sativa was evaluated for its
      hypolipidemic effects among menopausal women. In a randomised trial,
      hyperlipidemic menopausal women were assigned to treatment (n=19) or placebo
      groups (n=18), and given N. sativa or placebo for two months after their informed
      consents were sought. At baseline, blood samples were taken and at one month
      intervals thereafter until one month after the end of the study. RESULTS: The
      results showed that N. sativa significantly improved lipid profiles of menopausal
      women (decreased total cholesterol, low density lipoprotein cholesterol and
      triglyceride, and increased high density lipoprotein cholesterol) more than the
      placebo treatment over 2 months of intervention. One month after cessation of
      treatment, the lipid profiles in the N. sativa-treated group tended to change
      towards the pretreatment levels. CONCLUSIONS: N. sativa is thought to have
      multiple mechanisms of action and is cost-effective. Therefore, it could be used
      by menopausal women to remedy hypercholesterolemia, with likely more benefits
      than with single pharmacological agents that may cause side effects. The use of
      N. sativa as an alternative therapy for hypercholesterolemia could have profound
      impact on the management of CVD among menopausal women especially in countries
      where it is readily available.

PMID- 24685021
TI  - Image diagnosis of zoonotic onchocercosis by Onchocerca lupi.
AB  - Onchocerca lupi, a zoonotic nematode infecting the eyes of carnivores, has been
      increasingly reported in dogs from Europe and the USA. In order to improve the
      current status of knowledge on this neglected filarioid, diagnostic imaging tools
      (i.e., ultrasound scan, computed tomography and magnetic resonance imaging) are
      herein used to diagnose canine onchocercosis in two dogs, which scored positive
      for O. lupi microfilariae at the skin snip test and to assess the anatomical
      location of the nematode within the ocular apparatus. Results indicate that
      ultrasound tools are useful to address the diagnosis of O. lupi in dogs and to
      evaluate the localization of nodules or cysts containing the adult nematode. 

PMID- 24685022
TI  - The expression and activity of 5-LOX in the large intestine of horses harbouring
      encysted cyathostomin larvae.
AB  - Leukotrienes are products of the arachidonic acid metabolism and act as potent
      inflammatory mediators modulating the immune response and various physiological
      processes. This study evaluated the expression and activity of 5-lipoxygenase (5
      LOX), the enzyme that catalyzes the first two steps in the biosynthesis of
      leukotrienes, in horses infected by larval cyathostomins. Tissue samples from
      dorsal and ventral colon, and from the cecum were collected from 16 horses
      slaughtered for human consumption. Samples were analyzed to estimate the burdens
      of encysted cyathostomin larvae and adult luminal stages, and then processed for
      the evaluation of biochemical parameters. No significant differences were found
      in the protein expression and enzymatic activity of 5-LOX between animals
      harbouring only adult parasites and negative horses. The protein expression and
      enzyme activity of 5-LOX were significantly higher in horses harbouring encysted
      larvae in comparison with horses free of encysted larvae. Although preliminary,
      these results indicate that 5-LOX is an important mediator in the course of horse
      cyathostominosis and further studies are warranted to unveil the possible role
      this enzyme plays in the pathogenesis of horse cyathostominosis, and its
      potential as a diagnostic marker. 

PMID- 24685023
TI  - Molecular characterization of Cryptosporidium isolates from beef calves under one
      month of age over three successive years in one herd in western France.
AB  - Cohorts of pre-weaned calves were studied for Cryptosporidium infection over
      three successive years (2010-2012) in one beef cattle herd in western France.
      Each year 25-34 calves were sampled weekly from 3 days to one month of age in
      order to characterize oocyst output, Cryptosporidium species and clinical
      features associated with infection. Faecal samples were screened for the presence
      of oocysts using immunofluorescence analysis. DNA was extracted from positive
      samples and a PCR SSU rRNA followed by RFLP or sequencing was performed. For the
      subtyping of C. parvum, a gp60 PCR was carried out. Regardless of the year, 92
      100% of the animals excreted oocysts on at least one sampling date. Depending on
      the year of observation, the age of highest prevalence varied. In contrast, the
      peak of excretion was systematically observed almost at the same age (2nd-3rd
      week of life) with excretion levels ranging from between 100 and 1.7 *
      10(7)oocysts/g of faeces. Differences concerning clinical signs depending on the
      year of sampling were observed. Different species patterns were observed, with a
      predominance of C. bovis in the 1st year and a predominance of C. parvum in the
      last year. Moreover, two zoonotic subtypes of C. parvum, IIaA15G2R1 and
      IIaA18G2R1, were recorded in different years. This study shows that, in a given
      farm, the Cryptosporidium species and C. parvum subtypes identified as well as
      the prevalence of infection and level of excretion may vary greatly and show
      distinct patterns according to the year.

PMID- 24685024
TI  - Development and evaluation of an ITS1 "Touchdown" PCR for assessment of drug
      efficacy against animal African trypanosomosis.
AB  - Animal African trypanosomoses (AAT) are caused by flagellated protozoa of the
      Trypanosoma genus and contribute to considerable losses in animal production in
      Africa, Latin America and South East Asia. Trypanosoma congolense is considered
      the economically most important species. Drug resistant T. congolense strains
      present a threat to the control of AAT and have triggered research into discovery
      of novel trypanocides. In vivo assessment of trypanocidal efficacy relies on
      monitoring of treated animals with microscopic parasite detection methods. Since
      these methods have poor sensitivity, follow-up for up to 100 days after treatment
      is recommended to increase the chance of detecting recurrent parasitaemia waves.
      Molecular techniques are more amendable to high throughput processing and are
      generally more sensitive than microscopic detection, thus bearing the potential
      of shortening the 100-day follow up period. The study presents a "Touchdown" PCR
      targeting the internal transcribed spacer 1 of the ribosomal DNA (ITS1 TD PCR)
      that enables detection and discrimination of different Trypanosoma taxa in a
      single run due to variations in PCR product sizes. The assay achieves analytical
      sensitivity of 10 parasites per ml of blood for detection of T. congolense
      savannah type and T. brucei, and 100 parasites per ml of blood for detection of
      T. vivax in infected mouse blood. The ITS1 TD PCR was evaluated on cattle
      experimentally infected with T. congolense during an investigational new
      veterinary trypanocide drug efficacy study. ITS1 TD PCR demonstrated comparable
      performance to microscopy in verifying trypanocide treatment success, in which
      parasite DNA became undetectable in cured animals within two days post-treatment.
      ITS1 TD PCR detected parasite recrudescence three days earlier than microscopy
      and had a higher positivity rate than microscopy (84.85% versus 57.58%) in 66
      specimens of relapsing animals collected after treatments. Therefore, ITS1 TD PCR
      provides a useful tool in assessment of drug efficacy against T. congolense
      infection in cattle. As the assay bears the potential for detection of mixed
      infections, it may be applicable for drug efficacy studies and diagnostic
      discrimination of T. vivax and T. congolense against other pathogenic
      trypanosomes, including T. brucei, T. evansi and T. equiperdum. 

PMID- 24685026
TI  - [The immunization of hepatitis B vaccine and adverse events following
      immunization].

PMID- 24685025
TI  - Natural infection of the wild canid, Cerdocyon thous, with the piroplasmid
      Rangelia vitalii in Brazil.
AB  - Canine rangeliosis, caused by the piroplasmid protozoon Rangelia vitalii, is
      currently recognized as a reemerging disease that affects domestic dogs in
      Brazil. In the present study, piroplasmid infection was searched in wild canids
      (20 Cerdocyon thous and 4 Lycalopex gymnocercus) in Brazil. Molecular analysis,
      based on PCR and DNA sequencing of a portion of the 18S rRNA gene, revealed that
      30% (6/20) C. thous were infected by R. vitalii. Blood and bone marrow samples
      from one of the R. vitalii-infected C. thous were inoculated into a domestic dog,
      which developed clinical rangeliosis that was confirmed by molecular tests.
      However, the C. thous donor showed no clinical, hematological or biochemical
      alterations, even though its R. vitalii infection status was confirmed for at
      least 80 days. These observations suggest that R. vitalii is not as highly
      pathogenic for C. thous as it is for domestic dogs. Phylogenetic analysis
      inferred by the 18S rRNA gene placed R. vitalii embedded in the clade 'Babesia
      sensu stricto', consisting of a number of species that represent truly the genus
      Babesia. It is proposed that the species R. vitalii should be transferred to the
      genus Babesia. The present study expands our knowledge on the natural history of
      R. vitalii, suggesting that it might have a natural cycle involving the wild
      canid C. thous. Further studies are needed to confirm that C. thous is a natural
      reservoir of R. vitalii in Brazil.

PMID- 24685027
TI  - [Association between different types of obesity and cardiovascular risk factors
      in school-aged children].
AB  - OBJECTIVE: The aim of this paper was to analyze the association between different
      types of obesity and cardiovascular risk factors (CRFs)in school-aged children.
      METHODS: 3508 children aged 6-18 years old including 2 054 non-obese and 1 454
      obese children were chosen as the population under study, from Beijing Children
      and Adolescents Metabolic Syndrome Study. Demographic data was collected through
      questionnaires while height, weight, waist circumference, and blood pressure were
      measured through physical check-up. Fasting blood glucose and blood lipids were
      also tested. Children were divided into four groups:without obesity, with general
      obesity, with abdominal obesity and with combined obesity. CRFs including
      dyslipidemia, impaired fasting glucose (IFG), and hypertension were scored.
      Multiple linear regression and logistic regression analyses were performed to
      assess the association between different types of obesity and CRFs. RESULTS: From
      non-obese children, children under general-obesity, abdominal obesity and those
      with combined types of obesity, there appeared an increasing trend in the levels
      of blood pressure, blood glucose, and blood lipids, the prevalence dyslipidemia
      and hypertension (P < 0.001). There were no significant differences in the risks
      of IFG among four types of obesity. After controlling for age, sex, and puberty
      stage, when compared with non-obese children, those children with abdominal
      obesity or combined types of obesity had 1.54 and 2.51 times of risks to only one
      CRF, while generally obese children had similar risk of dyslipidemia. When
      compared to the non-obese ones, children with general obesity, abdominal obesity,
      or combined types of obesity showed 3.32, 2.21 and 7.42 times of risks to >= 2
      CRFs and 3.10, 3.67 and 10.75 times of risks to >= 3 CRFs. The cluster of CRFs
      increased with the levels of obesity (P < 0.001). CONCLUSION: Levels and cluster
      of CRFs were increasing along with the levels of obesity in school-aged children
      in Beijing. Children with combined types of obesity had the highest risk of
      clustering CRFs, followed by those with abdominal obesity and general obesity.

PMID- 24685028
TI  - [Detection rates of overweight and obesity in children and adolescents with
      different ethnicities in Xinjiang Uigur areas].
AB  - OBJECTIVE: To investigate the detection rates of overweight and obesity among
      Han,Uygur and Kazakh Children and adolescents in Xinjiang. METHODS: Random
      samples were used to analyze the detection rates on overweight and obesity based
      on data from Han,Uygur and Kazakh Children and adolescents aged 7-14 years from 3
      regions-Hetian, Kashi and Fuhai prefectures in Xinjiang Uygur Autonomous Region.
      Anthropometric data including weight and height was collected. Overweight and
      obesity were defined according to body mass index [BMI, weight (kg)/height (m2)]
      cutoffs recommended by the Chinese Working Group on Obesity for Children
      (WGOC)aged 7-14 years. RESULTS: The present study was performed in 11 894 Han,
      Uygur and Kazakh Children and adolescents aged 7-14 years. The overall prevalence
      rates of overweight and obesity were 5.6% and 2.9% respectively, which the
      difference between male and female was significant (chi2 = 39.765, P < 0.05).
      Different ethnic students of overweight and obesity rate showed differences, with
      detection rate of overweight among Kazakh students was 12.0% , higher than the
      other ethnic groups. The obesity detection rate was 7.2% among Han students,
      which was the highest of the three ethnic groups, with differences statistically
      significant(chi2 = 363.885, P < 0.05). Prevalence rates of both overweight and
      obesity decreased with increasing age in various ethnic groups, showing a clear
      downward trend, with the peak at 7-9 year-olds and the difference was
      statistically significant(chi2 = 101.479, P < 0.05). CONCLUSION: Both detection
      rates on overweight and obesity among children and adolescents were significantly
      lower in Xinjiang Uygur Autonomous Region than the national average level, with
      differences also seen in different ethnic, gender and age groups.

PMID- 24685029
TI  - [Growth pattern of Tibetan infants: one-year follow-up study after birth in rural
      Tibet].
AB  - OBJECTIVE: To investigate the growth pattern of rural Tibetan children in the
      first year after birth. METHODS: In rural area of Lhasa, Tibet, 252 subjects were
      recruited and their weight, length were measured longitudinally from birth to
      12th months of age. Frequency of monitoring reached 5 times in total and Ponderal
      index (PI)was calculated for each visit. Mixed model was used to analyze the
      changes of length and weight by gender after controlling for birth weight.
      RESULTS: Birth weight and length showed great influence on children's growth
      (weight: beta = -0.681 9, P < 0.000 1, length: beta = -0.957 1, P < 0.000 1).
      Weight and length of Tibetan male infants at each age point were lower than WHO
      new standard on growth and the Reference from 2005 National Survey on growth of
      children in China. The gap seemed widened by time but the gap between Tibetan
      female infants and Chinese standard narrowed 6 months after birth. Data showed
      that the higher PI of Tibetan infants than that of other Chinese infants which
      might infer that Tibetan infants had a more solid body mass under their own
      height. CONCLUSION: The growth pattern of Tibetan infants might have its own
      feature. Tibetan infants appeared to have had higher PI, which was contradictory
      to the general conclusion that poor growth and development status had been seen
      in Tibetan children.

PMID- 24685030
TI  - [Study on promotion of improvement regarding the nutritional status in Nakhi
      children and adolescents of Nakhi ethnicity].
AB  - OBJECTIVE: To analyze the improvement of nutrition status in children and
      adolescents of Nakhi ethnicity, in the last 25 years so as to put forward further
      suggestions for improvement. METHODS: 2 635 Nakhi students aged 7-18 years were
      selected from the 2010 national survey, with a group of Han students from the
      rural areas were randomly selected as controls. WHO-2006 reference was used to
      screen the prevalence of malnutrition, and compared with the control group.
      RESULTS: The prevalence rates in the Nakhi male and female students were 4.9% and
      4.7% for stunting, 5.6% and 4.6% for wasting, and 10.5% and 9.3% for total
      malnutrition, respectively. Changes on secular growth in both Nakhi and Han
      students in the rural areas were compared and the results showed that the
      superiority of Nakhi children was the cause for these disparities. CONCLUSION:
      Nutrition status of the Nakhi children was predicted and an optional future was
      displayed. Positive factors for causing these superiorities were summarized.
      Suggestions were also put forward regarding the formulation of balanced diet,
      improving the skills on preventive-cure, strengthening the local maternal-child
      healthcare services and the development of education on better bearing and
      rearing, etc.

PMID- 24685031
TI  - [Relationship between finger dermatoglyphics and body size indicators in
      adulthood among Chinese twin population from Qingdao and Lishui cities].
AB  - OBJECTIVE: To study the correlation between fingerprints and body size indicators
      in adulthood. METHODS: Samples were composed of twins from two sub-registries of
      Chinese National Twin Registry (CNTR), including 405 twin pairs in Lishui and 427
      twin pairs in Qingdao. All participants were asked to complete the field survey,
      consisting of questionnaire, physical examination and blood collection. From the
      832 twin pairs, those with complete and clear demographic prints were selected as
      the target population. Information of Fingerprints pixel on the demographic
      characteristics of these 100 twin pairs and their related adulthood body type
      indicators were finally chosen to form this research. Descriptive statistics and
      mixed linear model were used for data analyses. RESULTS: In the mixed linear
      models adjusted for age and sex, data showed that the body fat percentage of
      those who had arches was higher than those who did not have the arches (P =
      0.002), and those who had radial loops would have higher body fat percentage when
      compared with ones who did not (P = 0.041). After adjusted for age, there
      appeared no statistically significant correlation between radial loops and
      systolic pressure, but the correlations of arches (P = 0.031)and radial loops (P
      = 0.022) to diastolic pressure still remained statistically significant.
      CONCLUSION: Statistically significant correlations were found between fingerprint
      types and body size indicators, and the fingerprint types showed a useful tool to
      explore the effects of uterine environment on health status in one's adulthood.

PMID- 24685032
TI  - [How reproductive history of married women influencing the mortality rate of
      their children under 5 years in rural areas of Shaanxi province].
AB  - OBJECTIVE: To investigate the current status of reproductive history among
      married women and the mortality rate of children under 5 years. Influence of
      reproductive history among married women on mortality rate of their children
      under 5 years in rural areas in Shaanxi province was also studied. METHODS: A
      cross-sectional survey was conducted on reproductive history and mortality rate
      of their children under 5 years of age in five Fourth National-Level Poverty
      Stricken counties in Shaanxi province. Sample under study was chosen according to
      the three-stage stratified random sampling technique. RESULTS: A total number of
      4 732 married women were studied, with the average age of first birth as 23.65
      years, the average parity as 1.49, the average spacing between first and second
      child birth as 6.96 years and the average spacing between second and third child
      birth as 3.98 years. In children under 5 years of age among the surveyed women in
      2007-2010, 32.19% of the deaths in children under 5 years of age occurred during
      infancy while 70.21% of the infant deaths occurred during neonatal period. The
      mortality rates (1/1000)for newborns, infants and children under 5 years were
      6.710/00, 9.550/00, 29.670/00 respectively. Infant mortality rate of mother with
      multiple births was higher than the singletons (chi2 = 6.057, P = 0.014). Parity
      differences in mortality rate of children under 5 years were significant(chi2 =
      17.469, P < 0.001)and interval differences of births on infant mortality rate
      were also significant(chi2 = 13.137, P = 0.001). CONCLUSION: Fertility of rural
      women in Shaanxi was in good condition. The proportion that infant death was
      accounted for the total deaths of children under 5 years had declined, but the
      neonatal deaths still accounted for a big proportion of infant deaths. Infant
      mortality rate and mortality rate of children under 5 years old had declined,
      when compared to the national level in 2000, however, it was still higher than
      the city level. In terms of the fertility characteristics in women as multiple
      births, more parity and short spacing of births etc, were important factors of
      death of their children under 5 years of age.

PMID- 24685033
TI  - [Study on the psychological-health status and its relationship with social
      capital among left behind children in rural area, Macheng, Hubei province].
AB  - OBJECTIVE: To understand the status of mental health among left-behind children
      in rural area and to explore its relationship with social capital. METHODS: A
      sample of 1 031 left behind children, aged 10-18 years, was randomly selected
      from six schools of two townships in Macheng city of Hubei province where large
      number of rural parents were working in the urban area. Data from a cross
      sectional survey was collected among the sampled students from primary, middle
      and high schools, using self-designed questionnaires which targeting the 'left
      behind' condition and social capital Mental Health Inventory of Middle-School
      Students (MMHI-60). Chi-square test was used to compare the differences in mental
      health among different groups. Spearman correlation and logistical regression
      analysis were applied to assess the relationship between social capital and
      mental health. RESULTS: The prevalence of mental problems was 54.12%. Results
      from linear chi2 test indicated that the detection rates of mental problems were
      parallel with the monthly pocket money and the reduction in the frequency of
      contacting migrant father/mother (P < 0.01). Results from the multiple logistic
      regression analysis indicated that students who were senior(OR = 2.410-2.682, P <
      0.001), and who reported not caring about their parents (OR = 2.048-2.420, P <
      0.001)were at increased risks for mental health problems. After controlling the
      demographic characteristics and conditions of staying relevant factors, family
      social capital(OR = 0.845, 95%CI:0.801-0.891), neighborhood social capital (OR =
      0.867, 95%CI:0.826-0.910)and school social capital(OR = 0.893, 95%CI:0.863-0.923)
      were all associated with declined risks of mental health problems, in which the
      family social capital was the most important one. CONCLUSION: The prevalence of
      mental health problems was high among the left-behind children in rural area.
      Much attention should be paid to assist these children in improving their mental
      health status. One promising approach appeared to be improving social capitals
      which would include family social capital, neighborhood social capital, and
      school social capital to assist these children from avoiding mental health
      problems.

PMID- 24685034
TI  - [Evaluation on programs regarding the community-based management of hypertension
      and type 2 diabetes mellitus patients in eight provinces, China].
AB  - OBJECTIVE: To understand the situation and efficacy of community-based management
      programs on hypertension and type 2 diabetes mellitus patients in primary health
      service centers. METHODS: In eight provinces being selected, a stratified
      multistage random sampling method was used to survey 5 116 cases of hypertension
      patients and 3 586 cases of type 2 diabetes mellitus patients aged over 35 years
      who had been under the management program for over 1 year. Face-to-face
      questionnaire interview and physical and biochemical examination were applied to
      collect related information, blood pressure and situation of glucose control.
      RESULTS: The rates of management on hypertension patients and type 2 diabetes
      mellitus patients were 23.6% (urban:17.1%, rural:28.1%, chi2 = 27 195.33, P <
      0.001)and 19.1% (urban:14.1%, rural:23.8%, chi2 = 7 423.67, P < 0.001)while the
      standardized management rates were 61.1% (urban:63.3%, rural:58.6%, chi2 = 11.82,
      P < 0.001)and 59.0% (urban:61.5%, rural:55.6%, chi2 = 12.66, P < 0.001),
      respectively. Rate on blood pressure control among hypertension patients and the
      rate on fasting glucose control on type 2 diabetes mellitus patients were 50.3%
      (urban:62.0%, rural:36.6%, chi2 = 329.31, P < 0.001)and 53.9% (urban:60.8%,
      rural:44.7%, chi2 = 90.53, P < 0.001), respectively. Satisfaction rates for the
      management service of the hypertension patients and type 2 diabetes mellitus
      patients were 83.0% (urban:84.7% , rural: 80.7% , chi2 = 13.42, P < 0.001) and
      84.5% (urban:88.0% , rural:79.5% , chi2 = 43.90, P < 0.001), respectively.
      CONCLUSION: Efficiency was achieved to some extent in managing hypertension and
      type 2 diabetes mellitus patients in primary health service centers. Further
      improvement was expected on rates regarding management, standardized management
      and control on both blood pressure and glucose.

PMID- 24685035
TI  - [Quality of life and related factors among people living with HIV/AIDS in
      Guangdong province].
AB  - OBJECTIVE: To explore the quality of life and related factors among people living
      with HIV/AIDS in Guangdong province. METHODS: A total of 443 subjects older than
      age 18 who had been diagnosed as HIV/AIDS were recruited from AIDS Outpatient
      Clinic Departments in Guangzhou and Shenzhen. HIV/AIDS-targeted quality of
      life(HAT-QoL)scale was used to measure the quality of life on the patients.
      Nonparametric test method and multiple linear regression analysis were performed
      to explore the related factors. RESULTS: The average scores of the following nine
      domains of HIV/AIDS-targeted quality of life scales were:overall function as
      59.89 +/- 23.35, concerns on medication as 62.91 +/- 24.01, worries on factors as
      being disclosed, on health, on financial situation were 19.97 +/- 23.04, 54.05 +/
      12.24 and 35.94 +/- 26.45, respectively, trust on providers as 68.72 +/- 26.17,
      rate of understanding HIV as 61.46 +/- 25.72, on life satisfaction as 56.90 +/-
      25.30 and on sexual function as 50.82 +/- 23.86. Factors associated with quality
      of life would include sex, age, residential area, education, employment, marital
      status, complications, HAART-related prescriptions, route of infection and
      duration of HIV/AIDS etc. CONCLUSION: The quality of life among HIV/AIDS patients
      had declined, especially on worries related to disclosure and financial
      situation. More attention should be paid on those with poor education, low income
      and lack of family support in order to improve their quality of life and reducing
      mortality.

PMID- 24685036
TI  - [Epidemiological investigation on thyroid disease among fertile women in
      different iodine intake areas of Shanxi province].
AB  - OBJECTIVE: To understand the prevalence of thyroid diseases and its influencing
      factors of iodine on thyroid gland function and autoimmune among fertile women in
      different iodine intake areas. METHODS: Cross-sectional method was used for
      descriptive epidemiology. 236 women aged 19 to 45 years were sampled in 2011, in
      Shanxi province. Questionnaire was used to include general data on place, name,
      age etc. Sample of water from home, one time random urine sample and venous blood
      were collected to test the iodine contents using arsenic and cerium catalysis
      spectrophotometric methods. Finally, in blood, free triiodothyronine (FT3), free
      thyroxine (FT4), thyrotrophin (TSH) in blood were tested under auto-CLIA and anti
      thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) through radio
      immunological methods. RESULTS: 1)The urine iodine's medians were 486.9 ug/L for
      fertile women in high iodine areas, and 192.6 ug/L in low iodine areas, with
      difference on urine iodine level statistically significant (Z = -10.676, P =
      0.000). 2) Levels of blood FT3 and FT4 in women from high iodine areas were
      obviously lower than those from proper iodine areas(t = -2.884, P = 0.004; t = 
      2.862, P = 0.005), but the level of TSH in high iodine areas was higher than that
      of proper iodine areas(t = 2.332, P = 0.021). 3) In both areas, the rate of the
      thyroid dysfunction with positive antibodies was obviously higher than those with
      negative antibodies (chi2 = 20.941, P = 0.000;chi2 = 5.596, P = 0.018), while the
      rate of the thyroid dysfunction with positive antibodies and the level of TSH in
      the blood for high iodine women higher than those in women with proper iodine
      level(chi2 = 5.708, P = 0.37;t = -2.177, P = 0.031). 4)The morbidity rate of
      inferior clinical hyperthyroidism for women in high iodine areas was obviously
      higher than those in proper iodine areas(chi2 = 9.542, P = 0.003), while the
      morbidity rate of inferior clinical hypothyroidism for women with positive
      antibodies in two areas obviously higher than those with negative antibodies
      (chi2 = 17.264, P = 0.000; chi2 = 6.002, P = 0.044). CONCLUSION: Morbidity rate
      of inferior clinical hypothyroidism for women in high iodine areas was obviously
      higher than those in proper iodine areas, suggesting that there were potential
      risks of hypothyroidism for overdose iodine intake which causing the existence of
      positive thyroid antibodies. Monitoring programs on iodine nutrition and thyroid
      function among women living in high iodine areas should be strengthened.

PMID- 24685037
TI  - [Changes of iodine nutrition status and thyroid function among pregnant women in
      iodine sufficient rural area of Gansu province].
AB  - OBJECTIVE: To assess the iodine nutrition and thyroid function of pregnant women
      during different periods of pregnancy, to provide evidence for guiding iodine
      supplementation for them. METHODS: A cross-sectional survey was performed in 215
      pregnant women in Yongjing couty from May to June 2013. Samples of blood and
      random urine were collected, and serum thyrotrophin (TSH), free triiodothyronine
      (FT3), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO),
      antithyroglobulin ( anti-TG)and urinary iodine were measured. RESULTS: The
      medians of urinary iodine from the three groups of pregnant women(first, second
      and third trimester) were 189.8 ug/L, 152.5 ug/L and 144.9 ug/L respectively.
      With the exception of pregnant women in the third trimester, the urinary iodine
      medians of pregnant women in the first and second trimesters were within the 150
      249 ug/L range which was defined as optimal by WHO/UNICEF/ICCIDD. With the
      increase of gestational age, the level of FT3 decreased (P < 0.05), with the FT3
      levels in the first trimester were higher than those in the second or third
      trimester (P < 0.05). The difference of TSH levels among the three groups of
      pregnant women was statistically significant (P < 0.01), with a U-shaped curve
      seen between the iodine TSH levels and the gestational age. The medians of anti
      TG and anti-TPO appeared the lowest in the first trimester, and remained at a
      high level in women at second and third trimesters. Significant difference was
      seen in anti-TG, anti-TPO levels of the three groups of pregnant women (first,
      second and third trimester) (P < 0.01). The incidence of thyroid function
      disorder was 1.86%, including subclinical hypothyroidism accounted for 1.40%, and
      hypothyroidism accounted for 0.47%. The incidence of thyroid function disorder
      mainly appeared in the early pregnancy. Abnormal FT3, TSH, positive anti-TG and
      anti-TPO were mainly seen during early pregnancy. The changes of TSH, FT3, FT4,
      anti-TG and anti-TPO along with the changes of urine iodine levels were not
      obvious. CONCLUSION: With the increase of gestational age, the incidence of
      iodine deficiency also increased among pregnant women. Abnormal thyroid hormones,
      TSH, positive anti-TG and anti-TPO were mainly existed in the early pregnancy.
      Programs as monitoring urinary iodine as well as thyroid function targeting all
      the pregnant women should be carried out.

PMID- 24685038
TI  - [Epidemiological analysis on recent infected HIV-1 patients among newly reported
      HIV cases in Beijing, from 2009 to 2011].
AB  - OBJECTIVE: To understand the epidemiologic characteristics on newly reported HIV
      cases and those recently infected HIV-1 cases in the past few years in Beijing so
      as to find out their correlates. METHODS: All the qualified newly reported HIV
      serum samples from both the first quarters of 2009, 2010 and the second quarter
      of 2011 in Beijing, were tested using the BED HIV-1 incidence capture enzyme
      immunoassay (BED-CEIA) to identify those recent HIV-1 infection (BED positive)
      samples and related socio-demographic characteristics. The proportions of BED
      positives were determined and the correlates analyzed by SPSS software. RESULTS:
      The Annual qualified newly reported HIV serum samples of each year from Beijing
      were 274, 236 and 356, with BED positive rate among them as 35.0%, 31.8% and
      33.7%, respectively. The majority of newly reported HIV cases of each year were
      males (89.1%, 88.6%, 91.9%), range of age as 20-39 years (77.4%, 75.8%, 82.0%),
      Han nationality (77.7%, 88.6%, 85.7%), and most of them were not permanent
      residents of Beijing (74.1%, 80.5%, 2011 data missed). The proportions of
      patients through sexual transmission showed upward trend (67.5%, 76.2%, 86.8%).
      Especially in the 'man having sex with man' (MSM)group, it showed a significantly
      increase (44.9% , 45.3% , 62.6%). The proportions of injection drug users (15.3%,
      8.1%, 9.0%)declined to some extent during this period. Data from statistics
      indicated that the proportions of BED positives among newly reported HIV cases of
      each year were significantly correlated to factors as patients' sex, transmission
      route and source of samples, but not significantly correlated to patents' age or
      marital status. Male cases accounted for 96.9% and MSM accounted for 73.5% of all
      the BED-positives during 2009-2011. CONCLUSION: MSM accounted for both large
      portion of newly reported HIV cases and recent HIV-1 infections which suggested
      an increasing trend in 2009-2011. It seemed that the characteristic and changing
      trends of HIV epidemic in Beijing was oriented by MSM population in the last
      years.

PMID- 24685039
TI  - [Case classification in measles surveillance system under the Two-level Logistic
      Model].
AB  - OBJECTIVE: To study the prevalence rates of Rash and Febrile Illnesses (RFIs)
      including measles, rubella, scarlet fever, exanthema subitum and the differences
      among measles and other RFIs to tentatively formulate the logistic regression
      model through clinical manifestation. METHODS: All the suspected cases of
      measles, rubella, scarlet fever, exanthema subitum reported by the
      county/prefecture lever hospitals at four counties were collected during March
      2011 to February 2012. When setting laboratory confirmed measles as dependent
      variable and existed symptoms as independent variable, a logistic regression
      model was formulated and optimal operational point (OOP)chosen, according to the
      ROC curve. RESULTS: A total number of 551 cases were collected but the
      consistency of measles diagnosis between clinical and laboratory was not
      satisfied, with Kappa value = 0.349, same to the diagnosis of rubella. As for the
      result from the two-lever logistic regression model, symptoms that related to the
      confirmation of measles would include cough (OR = 5.75), conjunctivitis (OR =
      3.00), Koplik spot (OR = 7.52), lymphadenectasis(OR = 0.07), rash after fever (OR
      = 0.07). The area under ROC curve was 0.97 and the optimal operational point was
      0.249. CONCLUSION: A logistic regression model was formulated using the clinical
      symptoms which was resulted in better performance on prediction. As the sample
      size of this survey was small, the expansion on the scale of investigation and
      laboratory testings were needed before the types and components of measles
      related RFIs be clarified.

PMID- 24685040
TI  - [An investigation on a case of hand-foot-mouth disease caused by coxsackie-virus
      A6 associated with a vaccine-derived poliovirus co-infection].
AB  - OBJECTIVE: To identify the pathogen and characteristics on a case of hand-foot
      mouth disease (HFMD) caused by coxsackie-virus A6 (CA6) associated with vaccine
      derived poliovirus (VDPV) co-infection. METHODS: Field epidemiological study at
      the epidemic area was conducted and 16 stool samples including from the patient
      and close contacts were collected for isolation and identification of the
      enterovirus (EV). 21 stool samples from patients diagnosed as HFMD were collected
      in the same hospital at the same month to detect CA16,EV71, CA6 and PV by real
      time RT-PCR or RT-PCR. The VP1 gene of the CA6 was amplified by RT-PCR and PCR
      products were sequenced and analyzed. RESULTS: The patient showed only HFMD
      symptoms, but no symptoms related to acute flaccid paralysis (AFP). No EVs were
      isolated from 16 samples collected from the patient and close contacts. And no
      AFP cases were found by an active search. A total of 21 samples from patients
      diagnosed as HFMD were collected in the same hospital at the same month and 4
      were found to be EV71, 2 were CA16 and 15 (include the patient)were CA6. Only
      this patient was found to have had VDPV II infection. The CA6 VP1 gene was
      amplified from the HFMD patient and 9 other cases from the same hospital at the
      same month. Nucleotide sequences of the VP1 gene among the 9 strains shared 98.9%
      100.0% in homology and 96.0%-100.0% in the deduced amino acid sequences.
      Phylogenetic analysis of the VP1 sequences categorized the 9 strains into the
      same branch. There were 6 nucleotides changes including U2909A between the VP1
      region of the VDPV strain of the case and Sabin II. Results from phylogenetic
      analysis on the VP1 sequences indicated that the VDPV strain of the case was
      different from other VDPVs strains isolated in the world. CONCLUSION: This case
      was a HFMD which caused by CA6 co-infection with VDPV II and the VDPV was newly
      discovered. HFMD symptoms of the case were caused by CA6. The reason why this
      case did not have AFP symptoms was probably due the protective effect of IPV
      vaccine. No AFP cases were found by the active search for AFP cases conducted in
      the area, which indicated that VDPV did not cause virus circulation in this area.

PMID- 24685041
TI  - [Development of both multiple PCR and real-time SYBR green PCR for the detection
      of Vibrio cholerae non-O1/O139 serogroups].
AB  - OBJECTIVE: To develop methodology of both multiple PCR and real-time SYBR green
      PCR for the detection of Vibrio cholerae (V. cholerae) serogroups non-O1 and non
      O139. METHODS: The outer membrane protein gene (ompW) specific for V. cholerae,
      as well as O antigen rfb genes specific for both O1 and O139, were used for the
      design of the PCR primers. Both multiple PCR and real-time SYBR green PCR systems
      were used to detect both O1 and O139. Specific rfb genes and ompW were developed
      to evaluate their specificity, limit of detection, reproducibility and
      consistency. RESULTS: We established multiple PCR and real-time SYBR green PCR
      methods. According to the specific electrophoretic bands (multiple PCR) and the
      specific melt curve temperature (real-time SYBR green PCR), both methods could
      specifically detect the non-O1, non-O139 V. cholerae, and to differentiate them
      from O1,O139 V. cholerae, other five Vibrios and 3 intestinal bacteria. The
      detection limits were 7 * 10(4) cfu/ml (multiple PCR) and 7 * 102 cfu/ml(real
      time SYBR green PCR), with statistically significant difference seen (P < 0.05).
      For the reproducibility of real-time SYBR green PCR, the external coefficient
      variation ranging from 0.22% to 0.92% while the internal coefficient variation
      ranging from 0.27% to 1.41%. 370 strains of non-O1, non-O139 V. cholerae, were
      detected, with both consistency rates as 100% . CONCLUSION: Both multiple PCR and
      real-time SYBR green PCR could detect non-O1, non-O139 V. cholerae, rapidly,
      specifically, and reproducibly, that could all be used for the detection and
      identification of non-O1, non-O139 under different conditions.

PMID- 24685042
TI  - [The Clumping factor B gene typing in discriminating the strains of nosocomial
      acquired methicillin-resistant Staphylococcus aureus].
AB  - OBJECTIVE: To evaluate the clfB typing method in discriminating the ST239
      methicillin-resistant Staphylococcus aureus (MRSA) isolated from patients under
      nosocomial infection in Tianjin first central hospital so as to access the
      clinical risk factors and outcomes of the MRSA nosocomial infection from ICU and
      non-ICU departments. METHODS: Forty-two stains of MRSA with known SCCmec type
      were chosen in both ICU (n = 35) and non-ICU (n = 7) wards, from 2006 to 2012, of
      which MLST genotype was ST239. Clinical risk factors and rates on drug resistant
      to MRSA were counted, respectively. RESULTS: All the isolates of MRSA belonged to
      the same lineage 3 and 6 haplotypes, based on clfB variable-number tandom repeats
      typing. Thirty-five isolates from ICU belonged to 6 haplotypes, among which clfB3
      52, 3-52E, 3-50, 3-52C, 3-50A and 3-50E were accouted for 42.9%, 37.1%, 8.6%,
      5.7%, 2.9% and 2.9%, respectively. Seven isolates from non-ICU belonged to 3
      haplotypes, in which 3-52, 3-52E and 3-50 were accouted for 42.8%, 28.6%, 28.6%,
      respectively. When clfB typing was combined with SCCmec typing in use, results
      showed that the index of discrimination as 0.767, better than clfB (ID = 0.688)
      or SCCmec (ID = 0.303) used alone. SCCmec III -clfB3-52E seemed as the major
      clone among the 10 haplotypes of clfB/SCCmec typing, which was accounted for
      40.4% . There were significant differences on the length of hospitalization (P <
      0.005) and the duration of antibiotics use (P < 0.05) between ICU and non-ICU.
      CONCLUSION: The clfB typing method which was based on variable-numbers of tandom
      repeats showed powerful ability of resolution. It could also be combined with
      MLST and SCCmec typing to be used in local epidemiological investigations.

PMID- 24685043
TI  - [Impact the variability of blood pressure on the outcome of ischemic stroke
      patients upon discharge from the hospital].
AB  - OBJECTIVE: To explore the relationship between blood pressure variability and
      worsening functional outcomes of patients upon discharge from the hospitals.
      METHODS: The study cohort consisted of 404 patients who presented to Second
      Affiliated Hospital of Harbin Medical University with ischemic stroke during
      March 2012-March 2013. Systolic BP and diastolic BP were measured for each
      patient from admission to the fifth day and coefficient of variation blood
      pressure calculated. Disability at discharge was measured by the modified Rankin
      score (mRs). Chi-square test, t-test and multivariate logistic regression
      analysis were performed. RESULTS: After adjustment for potential confounding
      factors including age, sex, activity, smoking, alcohol intake,BMI, heart rate,
      hypertension, diabetes mellitus, stroke history, lipid parameters, homocysteine
      and FPG, results from the multivariate logistic regression analysis showed that
      when DBP variability was greater than 9, it was associated with a significantly
      worse functional outcome at hospital discharge compared with those less than 9,
      with the odds ratio as 1.70 (95%CI:1.02-2.84). When comparing the ones that DBP
      variability more than 10 with the ones less than 10, the odds ratio was 1.86 (95%
      CI:1.11-3.13). However, there was no significant association seen between SBP
      variability and the worse functional outcome at hospital discharge. CONCLUSION:
      Blood pressure variability might be associated with ischemic stroke outcome at
      hospital discharge but needed more evidence to approve.

PMID- 24685044
TI  - [Influential factors on congenital gastrointestinal malformation:a hospital-based
      case-control study].
AB  - OBJECTIVE: To investigate the influential factors on congenital gastrointestinal
      malformation and to provide evidences for prevention. METHODS: A hospital-based
      case-control study was conducted among infants with or without congenital
      gastrointestinal malformation at Children's hospital of Hunan province, from
      April 2011 to August 2012. Parents of 120 cases with congenital gastrointestinal
      malformation and another 170 controls were asked to fill in a questionnaire. Data
      was analyzed using SPSS 18.0 software. RESULTS: Congenital gastrointestinal
      malformation was associated with intakes of maternal medication (OR = 3.35,
      95%CI:1.51-7.41) and folic acid (OR = 0.28, 95%CI:0.15-0.52), exposure to paints
      (OR = 5.05, 95%CI:1.32-19.29) and pesticides (OR = 15.20, 95%CI:1.55-148.99)
      prior to or during pregnancy, and also associated with medication intake of the
      father (OR = 3.70, 95% CI:1.13-12.10), smoking (OR = 2.39, 95% CI:1.24-4.62),
      drinking alcohol (OR = 2.47, 95% CI:1.20-5.07), exposure to the agents for indoor
      cleaning (OR = 16.42, 95% CI:1.71-157.92) and exposure to paints (OR = 9.92, 95%
      CI:2.66-36.98) before conception. CONCLUSION: Congenital gastrointestinal
      malformation was affected by multiple factors. Potential risk factors for
      congenital gastrointestinal malformation would include intakes of medication by
      the pregnant mother, exposure to paints exposure and pesticide exposure before or
      during pregnancy, and medication intake by the father, smoking, drinking alcohol,
      exposure to indoor cleaning agents/paint before conception. The amount of folic
      acid intake by mother before or during pregnancy was likely to reduce the risk
      for congenital gastrointestinal malformation.

PMID- 24685045
TI  - [Dynamic monitoring on ovarian function among patients having had cervical
      squamous cell carcinoma transposition surgery].
AB  - To investigate the changes in ovarian function and the radiotherapeutic influence
      on ovarian function on patients with cervical squamous cell carcinoma. METHODS:
      We retrospectively analyzed 53 cases of cervical cancer patients FIGO staging I
      B1- II B who had received ovarian transposition surgery at the Maternal and Child
      Health Hospital of Jiangxi province from January 2009 to June 2012. All the
      patients included in the study were FIGO staging I B1- II B and had undergone
      radiation therapy, including 38 staging I B1- II A2 cervical cancer patients
      receiving chemo-therapy after radical radiotherapy due to the presence of risk
      factors and other 15 patients with stage II B to radical concurrent
      chemoradiotherapy ovarian transposition. Ovarian transposition methods would
      include laparoscopic ovarian transposition and transabdominal ovarian
      transposition. 15 concurrent patients with stage II B who currently receiving
      chemo-radiotherapy were under laparoscopic ovarian transposition. Among the 38
      radical hysterectomy patients, 31 were having abdominal ovarian transposition,
      and the remaining 7 cases were laparoscopic. All the 53 patients had undergone
      radiotherapy. The levels of serum female hormones FSH, LH, E2 were determined to
      monitor the ovarian endocrine function. RESULTS: According to FIGO staging, 18
      cases were stage I B1, 15 cases I B2, 3 cases II A1, 2 cases II A2 and 15 cases
      II B. Patients' age range was from 28 to 44 years old, with an average of 37.7
      years, median age as 38 years. 14 patients (63.6%) were still normal ovarian
      function after radiotherapy by laparoscopic ovarian transposition, which was
      100.0% before radiotherapy. There was a significant difference (P < 0.05)compared
      with before radiotherapy. After transabdominal ovarian transposition surgery and
      radiotherapy, normal ovarian function 22 cases (71.0%), and there was a
      significant difference (P < 0.05) compared with before radiotherapy. No
      significant difference was found with regard to the proportion of normal ovarian
      function after radiotherapy between the two groups of patients with laparoscopic
      and transabdominal ovarian transposition (P > 0.05). CONCLUSION: For the young
      cervical cancer patients, even with ovarian transposition, ovarian dysfunction
      was still evident after radiotherapy. There was no significant difference between
      laparoscopic and transabdominal ovarian transposition.

PMID- 24685046
TI  - [Recent advances in molecular epidemiology of Orientia tsutsugamushi in China].

PMID- 24685047
TI  - [Overview on the practice and characteristics of large prospective cohort
      studies].

PMID- 24685048
TI  - [Progress on methodology of adjusting survival curves].

PMID- 24685049
TI  - Local cattle movements in response to ongoing bovine tuberculosis zonation and
      regulations in Michigan, USA.
AB  - Bovine tuberculosis (Mycobacterium bovis) is an ongoing management issue in the
      state of Michigan with eradication from livestock as the ultimate goal.
      Eradication has been a challenge owing to the presence of a wildlife reservoir;
      competing interests in managing the livestock and wildlife hosts; and many
      uncertainties in transmission dynamics of M. bovis. One of the cornerstones of
      the eradication effort has been to stop movement of infected cattle among farms
      by imposing strict pre-movement testing on cattle being moved within, into and
      out of the Modified Accredited Zone (MAZ) in northeastern Michigan. In addition
      to pre-movement tuberculosis testing, detailed information about the origin and
      destination premises of all movements within the MAZ has been recorded in
      Michigan. The aim of this study was to describe the farm-to-farm movements of
      cattle within the MAZ, report changes in the network of movements during a 6-year
      period when the MAZ was a constant size (2004-2009), and examine changes in
      cattle movement patterns when the MAZ was reduced from 11 to 5 counties in 2010.
      Non-slaughter cattle movement within the MAZ was characterized by predominantly
      local movements at a sub-county scale. Premises that shipped cattle were
      primarily senders or receivers, but rarely both. From 2004 to 2009, the number of
      cattle shipped, size of shipments, number of shipments and distance of shipments
      decreased; there was little change in the network patterns of interaction among
      individual premises; and interactions among all premises became more
      disconnected. After accounting for MAZ size, there were also no changes in cattle
      movement network patterns following the reduction of the MAZ in 2010. The
      movement of cattle was likely not a key risk factor in bTB spread among premises
      in the MAZ during the study period and the effect of zonation and movement
      regulations appeared to further reduce the risk of tuberculosis spread via cattle
      movements among farms in Michigan's MAZ. 

PMID- 24685050
TI  - The ameliorating effects of long-term electroacupuncture on cardiovascular
      remodeling in spontaneously hypertensive rats.
AB  - BACKGROUND: The purpose of this study was to investigate the inhibitory effects
      of long-term electroacupuncture at BaiHui (DU20) and ZuSanLi (ST36) on
      cardiovascular remodeling in spontaneously hypertensive rats (SHR) and underlying
      mechanisms. METHODS: 6-weeks-old SHR or Wistar male rats were randomly, divided
      into 6 groups: the control group (SHR/Wistar), the non-acupoint
      electroacupuncture stimulation group (SHR-NAP/Wistar-NAP) and the
      electroacupuncture stimulation at DU20 and ST36 group (SHR-AP/Wistar-AP), 24 rats
      in each group. Rats were treated with or without electroacupuncture at DU20 and
      ST36, once every other day for a period of 8 weeks. The mean arterial pressure
      (MAP) was measured once every 2 weeks. By the end of the 8th week, the left
      ventricular structure and function were assessed by echocardiography. The content
      of angiotensin II (Ang II), endothelin-1 (ET-1) and nitric oxide (NO) in the
      plasma was determined using enzyme-linked immunosorbent assay. Histological
      studies on the heart and the ascending aorta were performed. The expression of
      angiotensin II type 1 receptor (AT1R), endothelin-1 type A receptor (ETAR), eNOS
      and iNOS in rat myocardium and ascending aorta was investigated by Western
      blotting. RESULTS: The MAP in SHR increased linearly over the observation period
      and significantly reduced following electroacupuncture as compared with sham
      control SHR rats, while no difference in MAP was observed in Wistar rats between
      electroacupuncture and sham control. The aortic wall thickness, cardiac
      hypertrophy and increased collagen level in SHR were attenuated by long term
      electroacupuncture. The content of Ang II, ET-1 in the plasma decreased, but the
      content of NO increased after electroacupuncture stimulation in SHR. Long term
      electroacupuncture significantly inhibited the expression of AT1R, ETAR and iNOS,
      whereas increased eNOS expression, in myocardium and ascending aorta of SHR.
      CONCLUSIONS: The long term electroacupuncture stimulation at DU20 and ST36
      relieves the increased MAP and cardiovascular abnormality in both structure and
      function in SHR, this beneficial action is most likely mediated via modulation of
      AT1R-AT1R-ET-1-ETAR and NOS/NO pathway.

PMID- 24685051
TI  - Deep transcranial magnetic stimulation in a woman with chronic tinnitus: clinical
      and FMRI findings. Seeking relief from a symptom and finding vivid memories by
      serendipity.

PMID- 24685052
TI  - Associations between young children's perceived and actual ball skill competence
      and physical activity.
AB  - OBJECTIVES: The relationship between actual and perceived object control
      competence (ball skills) and the contribution to young children's physical
      activity is not known. DESIGN: Cross sectional study. METHODS: The Test Gross
      Motor Development-2 assessed actual object control competence and a modified
      version of the Pictorial Scale of Perceived Competence and Social Acceptance for
      Young Children assessed perceived object control competence. Moderate- to
      vigorous-intensity physical activity was measured via accelerometry. Three mixed
      regression models were performed: (i) object control competence as the predictor
      and the outcome as perceived object control, (ii) perceived object control
      competence as the predictor and the outcome moderate to vigorous physical
      activity and (iii) actual object control as the predictor and the outcome
      moderate to vigorous physical activity. Models adjusted for school clustering,
      monitor wear time, sex and age. Interactions between respective predictor
      variables and sex were performed if warranted. A total of 102 children (56% boys,
      44% girls) aged 4-8 years (M 6.3, SD 0.92) completed assessments. RESULTS: Girls
      had lower perceived and actual object control competence and were less active
      than boys. Actual object control competence was positively associated with
      perceived object control competence (B=0.11, t(96)=2.25, p<0.001, p=0.027) and
      this relationship did not differ by sex (p=0.449); however, neither actual
      (p=0.092) nor perceived object control competence (p=0.827) were associated with
      moderate to vigorous physical activity. DISCUSSION: Young children's perceived
      ball skill abilities appear to relate to actual competence; however, these
      measures were not associated with physical activity. In older children, object
      control skill is associated with physical activity so targeting young children's
      object control skills is an intervention priority.

PMID- 24685053
TI  - Comparison of lateral and posterior surgical approach in management of extra
      articular distal humeral shaft fractures.
AB  - OBJECTIVE: The objective of this study was to compare treatment results and
      complication rates between lateral and posterior approaches in surgical treatment
      of extra-articular distal humeral shaft fractures. MATERIAL AND METHODS: Between
      June 2008 and May 2012, a total of 68 patients with extra-articular distal
      humeral shaft fractures were treated by lateral and posterior approaches. Of the
      patients, 30 were operated by a lateral approach (group I) and 26 patients were
      operated by a posterior approach (group II). There was no statistical
      significance between the two groups in sex distribution, age, the mechanism of
      the injury, injured arms, AO/ASIF (Arbeitsgemeinschaft fur
      Osteosynthesefragen/Association for the Study of Internal Fixation)
      classification, and the time from injury to surgery (P>0.05). Operation time,
      intraoperative bleeding volume, hospitalisation, clinical outcomes, and
      complications were compared between the two groups. The elbow functional results
      were evaluated by the Mayo Elbow Performance Score (MEPS). RESULTS: All patients
      were followed up. The average of follow-up in group I was 15.53+/-2.636 months
      (range, 12-22 months), and was 16.12+/-2.889 months (range, 12-22 months) in
      group II. There was no significant difference in the operation time,
      intraoperative bleeding time, and hospitalisation between the two groups
      (P>0.05). In group I, the mean time of bone union was 12.87+/-1.852 weeks (range,
      10-16 weeks), the mean degrees of elbow flexion was 139.20 degrees +/-3.274
      degrees  (range, 134-146 degrees ), the mean degrees of elbow extension was 4.77
      degrees +/-1.906 degrees  (range, 0-8 degrees ), and the mean points of MEPS was
      87.00+/-7.724 (range, 70-100 points). In group II, the mean time of bone union
      was 12.96+/-2.218 weeks (range, 10-16 weeks), the mean degrees of elbow flexion
      was 137.85 degrees +/-4.076 degrees  (range, 130-145 degrees ), the mean degrees
      of elbow extension was 5.15 degrees +/-2.327 degrees  (range, 0-9 degrees ), and
      the mean points of MEPS was 86.15+/-7.656 (range, 70-100 points). There was no
      significant difference in the bone union, range of elbow flexion, range of elbow
      extension and MEPS between the two groups (P>0.05). The overall complication rate
      in group I was lower than that in group II (P=0.041). CONCLUSIONS: Both lateral
      and posterior surgical approaches acquired satisfied treatment results in the
      management of extra-articular distal humeral shaft fractures, and there was a
      lower complication rate using the lateral approach.

PMID- 24685054
TI  - Sphingosine kinase 1 improves cutaneous wound healing in diabetic rats.
AB  - BACKGROUND: Diabetes is one of the most prevalent human metabolic diseases. Wound
      healing in diabetes is frequently impaired and treatment remains challenging.
      Sphingolipid metabolites play important roles in the regulation of glucose
      metabolism. SPK1 is the key enzyme in the sphingolipid metabolic pathway. S1P/SPK
      plays a pivotal role in the signalling pathways of diverse cellular processes
      including proliferation, differentiation, migration, apoptosis in diverse cell
      types. METHODS: To investigate the role of sphingosine kinase 1 (SPK1) in skin
      injury, plasmids containing the SPK1 gene (pcDNA3-FLAG-SPK1) were applied to
      cutaneous wounds on a streptozotocin-induced diabetic rat model over a 21-day
      period. The wound area and rate of wound healing were determined. The
      histopathological features of the healed wounds were also observed, and SPK1
      expression in the skin was detected by immunohistochemistry. RESULTS: There was a
      significant decrease in wound area in diabetic rats treated with 125 and
      60MUg/wound pcDNA3-FLAG-SPK1 (P<0.001-0.01). The mean sizes of the wounds were
      0.67+/-0.15cm(2), 0.83+/-0.18cm(2), and 1.09+/-0.23cm(2) in both treated and
      diabetic control group at the 7th day post-treatment respectively. In addition,
      wound healing in diabetic rats of test group was accelerated. At the 7th day, the
      mean rates of healing were 73.2+/-5.7% and 66+/-7.3% in test group of 125 and
      60MUg/wound respectively, and 55.4+/-9.9% in diabetic control group (P<0.001
      0.01). Histology revealed that tissue sections from the treated diabetic rats
      contained more granulation tissue and capillaries than that of the control rats.
      There was high SPK1 expression in the skin of the treated diabetic rats.
      CONCLUSIONS: SPK1 gene therapy may represent a novel approach to cutaneous wound
      healing.

PMID- 24685056
TI  - Radial neck fracture presenting to a Chiropractic clinic: a case report and
      literature review.
AB  - OBJECTIVE: The purpose of this case report is to describe a patient that
      presented with a Mason type II radial neck fracture approximately three weeks
      following a traumatic injury. CLINICAL FEATURES: A 59-year old female presented
      to a chiropractic practice with complaints of left lateral elbow pain distal to
      the lateral epicondyle of the humerus and pain provocation with pronation,
      supination and weight bearing. The complaint originated three weeks prior
      following a fall on her left elbow while hiking. INTERVENTION AND OUTCOME: Plain
      film radiographs of the left elbow and forearm revealed a transverse fracture of
      the radial neck with 2mm displacement--classified as a Mason Type II fracture.
      The patient was referred for medical follow-up with an orthopedist. CONCLUSION:
      This report discusses triage of an elbow fracture presenting to a chiropractic
      clinic. This case study demonstrates the thorough clinical examination, imaging
      and decision making that assisted in appropriate patient diagnosis and
      management.

PMID- 24685055
TI  - Characterization of TgPuf1, a member of the Puf family RNA-binding proteins from
      Toxoplasma gondii.
AB  - BACKGROUND: Puf proteins act as translational regulators and affect many cellular
      processes in a wide range of eukaryotic organisms. Although Puf proteins have
      been well characterized in many model systems, little is known about the
      structural and functional characteristics of Puf proteins in the parasite
      Toxoplasma gondii. METHODS: Using a combination of conventional molecular
      approaches, we generated endogenous TgPuf1 tagged with hemagglutinin (HA) epitope
      and investigated the TgPuf1 expression levels and localization in the tachyzoites
      and bradyzoites. We used RNA Electrophoretic Mobility Shfit Assay (EMSA) to
      determine whether the recombination TgPuf1 has conserverd RNA binding activity
      and specificity. RESULTS: TgPuf1 was expressed at a significantly higher level in
      bradyzoites than in tachyzoites. TgPuf1 protein was predominantly localized
      within the cytoplasm and showed a much more granular cytoplasmic staining pattern
      in bradyzoites. The recombinant Puf domain of TgPuf1 showed strong binding
      affinity to two RNA fragments containing Puf-binding motifs from other organisms
      as artificial target sequences. However, two point mutations in the core Puf
      binding motif resulted in a significant reduction in binding affinity, indicating
      that TgPuf1 also binds to conserved Puf-binding motif. CONCLUSIONS: TgPuf1
      appears to exhibit different expression levels in the tachyzoites and
      bradyzoites, suggesting that TgPuf1 may function in regulating the proliferation
      or/and differentiation that are important in providing parasites with the ability
      to respond rapidly to changes in environmental conditions. This study provides a
      starting point for elucidating the function of TgPuf1 during parasite
      development.

PMID- 24685057
TI  - Screw loosening and iliotibial band friction after posterolateral corner
      reconstruction.
AB  - BACKGROUND: Many reconstruction techniques have already been developed for
      treating posterolateral corner (PLC) injuries, with still no consensus regarding
      what would be the best option. Some techniques use non-bone tunnel fixation,
      attaching the graft to the femur using a cortical screw with toothed washer. The
      main objective of the present study is to evaluate complications related to
      fixation performed by a screw and toothed washer technique. METHODS: A
      prospective study with surgical reconstruction of the PLC structures of the knee
      between January 2008 and December 2009 was performed. PLC reconstruction included
      reconstruction of the lateral collateral ligament, popliteofibular ligament and
      popliteal muscle tendon. Fixation of the grafts in the femur was achieved by
      means of a 4.5mm screw with a toothed washer. The assessments were done using the
      following methods: objective IKDC, subjective IKDC, Lysholm and Tegner.
      Radiographic evaluations were performed immediately after the operation, at 3, 6
      and 12months after surgery, and yearly thereafter. Complications were documented.
      RESULTS: The mean subjective IKDC score after the operation was 69.2; Lysholm
      scale was 80.7. Two patients presented failure of reconstructions of the PLC. In
      the radiographic evaluations, signs of loosening of the screw with toothed washer
      in the femur were observed in eight cases (66.6%). Six patients (50%) complained
      of lateral pain after the operation. CONCLUSION: The technique of femoral
      fixation was shown to be efficient in restoration of stability. However there was
      a high rate of complications secondary to implant, such as loosening of the
      screws and iliotibial tract friction. LEVEL OF EVIDENCE: Case series, leve IV.

PMID- 24685060
TI  - Early hospital admission and treatment onset may positively affect spontaneous
      passage of ureteral stones in patients with renal colic.
AB  - OBJECTIVE: To evaluate the impact of early hospital admission and onset of
      medical expulsive therapy (MET) in spontaneous passage of ureteral stones causing
      renal colic. METHODS: We recruited 392 patients referred to the emergency room
      with symptoms of renal colic. All patients received standard MET of oral
      tamsulosin 0.4 mg at the time of diagnosis. In group A, patients who received MET
      in <2 hours from the symptom onset were included, whereas group B consisted of
      patients treated in >2 hours. The association of MET onset and stone-free rates
      after 6 weeks of follow-up was evaluated. Early MET onset predictive impact on
      spontaneous stone passage was evaluated as well. RESULTS: The stone-free rate in
      group A and B patients was 71.2% and 59.7% (P=.018), respectively. A significant
      association was observed between spontaneous calculus elimination and stone size
      (P<=.001), location within the ureter (P=.007), and the interval between pain
      onset and pharmaceutical management (P=.018). Patients who received a late-onset
      MET had an increased risk to develop febrile upper urinary tract infection during
      the follow-up period (P=.040). In the multivariate analysis, size (P<=.001) and
      early therapy onset (P=.019) were statistically important predictors for stone
      free status after the surveillance period. CONCLUSION: Patients with renal colic
      who admitted to the emergency department earlier since symptom onset may have
      increased potential to be stone free during the surveillance period.

PMID- 24685058
TI  - A phase Ib study of combined VEGFR and mTOR inhibition with vatalanib and
      everolimus in patients with advanced renal cell carcinoma.
AB  - BACKGROUND: Vatalanib is an oral vascular endothelial growth factor receptor
      (VEGFR) tyrosine kinase inhibitor (TKI), whereas everolimus inhibits mammalian
      target of rapamycin (mTOR). Combination therapy with VEGFR and mTOR inhibitors
      has not been well tolerated to date but may have efficacy in renal cell carcinoma
      (RCC). PATIENTS AND METHODS: A phase Ib study of vatalanib and everolimus was
      performed in patients with advanced solid tumors to determine the maximum
      tolerated dose (MTD), safety, and tolerability of the combination. A dose
      expansion cohort of 20 patients with metastatic RCC was studied to further define
      toxicity and preliminary efficacy in patients with RCC. RESULTS: We evaluated 32
      patients over 3 dose levels and a dose-expansion cohort. The most common
      toxicities of any grade were proteinuria, fatigue, hypertriglyceridemia, nausea,
      and vomiting. Dose-limiting toxicities (DLTs) included severe hypertension,
      diarrhea, neutropenia, mucositis, and fatigue. The MTD for the combination was
      vatalanib 1000 mg daily and everolimus 5 mg daily. In all patients, median
      overall survival (OS) was 16.3 months. In patients with RCC, median progression
      free survival (PFS) was 5.8 months, and OS was 16.5 months. OS was significantly
      better in treatment-naive patients (25.1 months) compared with patients who had
      received previous vascular endothelial growth factor (VEGF)-targeted therapy (6.3
      months). Seven of 24 (29.2%) evaluable patients demonstrated a partial response,
      and an additional 15 patients exhibited stable disease. Long-term tolerability (>
      1 year) was demonstrated in 19% of patients. CONCLUSION: Relevant doses of
      vatalanib and everolimus were achieved in combination, with expected toxicities.
      A substantial number of patients with RCC achieved an objective response in the
      treatment-naive setting, with prolonged tolerability and survival. Further
      comparative phase II/III studies of specifically targeted VEGF and mTOR inhibitor
      combinations may be warranted in patients with RCC.

PMID- 24685059
TI  - The long-term incidence of urinary tract infection after endoscopic management of
      vesicoureteral reflux.
AB  - OBJECTIVE: To evaluate the long-term urinary tract infection (UTI) rates after
      endoscopic correction of vesicoureteral reflux and the possible risk factors for
      urinary infection. MATERIALS AND METHODS: A retrospective study of patients who
      underwent endoscopic management of vesicoureteral reflux at a single institution
      from 2001 to 2011 was performed. Patients were followed up for a minimum of 1
      year. Voiding cystourethrograms were completed 3 months postoperatively. UTI
      questionnaire pertaining to the patient's UTI history before and after the
      surgery was mailed to each patient. Data were first evaluated looking only at
      culture-confirmed UTIs, and a second analysis included all patient-reported and
      culture-confirmed urinary infections. Factors considered in the analysis included
      sex, age, preoperative dimercaptosuccinic acid (DMSA) scan, reflux on
      postoperative voiding cystourethrogram, voiding dysfunction, and preoperative
      reflux grade. RESULTS: Data on 175 patients for a minimum of 1 year were
      collected. There were 34 of 175 confirmed UTIs after endoscopic management, and
      11 confirmed febrile UTIs. There were no significant predictors of febrile or
      afebrile UTIs in this group. Fifty-three of 175 patients (30%) experienced any
      UTI, 19 of which were febrile (10%). In this group, recurrent reflux was the only
      significant predictor of UTI (P=.03) and febrile UTIs (P=.04). Patients with more
      UTIs preoperatively were more likely to have a postoperative febrile UTI.
      CONCLUSION: Rates of UTI and febrile UTI in endoscopic management are similar and
      no better than those for open ureteral reimplantation. Longer follow-up suggests
      an association of recurrent reflux and preoperative UTI rates as predictors of
      postoperative febrile UTIs. These patients benefit from closer postoperative
      observation.

PMID- 24685061
TI  - Surgical management of genitoperineal hidradenitis suppurativa in men.
AB  - OBJECTIVE: To report our successful experience in treating genital and perineal
      hidradenitis suppurativa (HS) and its sequelae including localized chronic
      lymphedema. We describe our method of diseased tissue resection and wound defect
      coverage with local flaps and split-thickness skin grafts (STSG). METHODS: From
      2004 to 2012, we treated 6 patients with genital and perineal HS with radical
      resection of diseased tissue. Wound coverage was performed with skin flaps and/or
      STSGs. RESULTS: Two patients had enough normal neighboring skin for local flap
      coverage of their wound defect. Four others had more extensive disease requiring
      STSG coverage. Two patients with secondary penile skin lymphedema required STSG
      for penile shaft reconstruction. All patients achieved excellent cosmetic
      results. There was one recurrence that required repeat resection and wound
      coverage. No wound complications occurred at the STSG donor site. Successful STSG
      "take" on the scrotum and penis ranged from 90% to 100% (mean 98%). Wound
      complications from local flap closure were clinically insignificant and include
      small (<=2 cm) areas of wound breakdown with no evidence of infection in 3
      patients (50%). CONCLUSION: Genitoperineal HS is a debilitating and disfiguring
      disease that results in the need for repeated abscess drainage operations,
      chronically painful skin boils, and chronic foul-smelling infectious discharge.
      It can be associated with lymphedema of surrounding tissues, requiring removal of
      tissues not originally affected by the disease. The use of complete resection and
      reconstruction with skin flaps and grafts provides a viable treatment option for
      these patients.

PMID- 24685062
TI  - Ethnoveterinary herbal remedies used by farmers in four north-eastern Swiss
      cantons (St. Gallen, Thurgau, Appenzell Innerrhoden and Appenzell Ausserrhoden).
AB  - BACKGROUND: Very few ethnoveterinary surveys have been conducted in central
      Europe. However, traditional knowledge on the use of medicinal plants might be an
      option for future concepts in treatment of livestock diseases. Therefore the aim
      of this study was to document and analyse the traditional knowledge and use of
      homemade herbal remedies for livestock by farmers in four Swiss cantons. METHODS:
      Research was conducted in 2012. Fifty farmers on 38 farms were interviewed with
      the aid of semistructured interviews. Detailed information about the plants used
      and their mode of preparation were documented as well as dosage, route of
      administration, category of use, origin of knowledge, frequency of use, and
      satisfaction with the treatment. RESULTS: In total, 490 homemade remedies were
      collected. Out of these, 315 homemade remedies contained only one plant species
      (homemade single species herbal remedies, HSHR), which are presented in this
      paper. Seventy six species from 44 botanical families were mentioned. The most
      HSHR were quoted for the families of Asteraceae, Polygonaceae and Urticaceae. The
      plant species with the highest number of HSHRs were Matricaria recutita L.,
      Calendula officinalis L., Rumex obtusifolius L. and Urtica dioica L. For each
      HSHR, one to eight different applications were enumerated. A total of 428
      applications were documented, the majority of which were used to treat cattle.
      The main applications were in treatment of skin afflictions and sores, followed
      by gastrointestinal disorders and metabolic dysfunctions. Topical administration
      was most frequently used, followed by oral administration. In nearly half of the
      cases the knowledge on preparing and using herbal remedies was from forefathers
      and relatives. More than one third of the applications were used more than ten
      times during the last five years, and in about sixty percent of the cases, the
      last application was during the last year preceding the interviews. CONCLUSIONS:
      Traditional knowledge of farmers about the use of medicinal plants to treat
      livestock exists in north-eastern Switzerland. Homemade herbal remedies based on
      this knowledge are being used. The interviewed farmers were satisfied with the
      outcome of the applications.

PMID- 24685063
TI  - Utility of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations
      in obese diabetic individuals before and after weight loss.

PMID- 24685064
TI  - Lowering blood pressure to lower the risk of cardiovascular events in CKD.

PMID- 24685065
TI  - A systematic review of the management and outcome of toxic epidermal necrolysis
      treated in burns centres.
AB  - INTRODUCTION: Toxic epidermal necrolysis (TEN) is a rare condition characterised
      by mucocutaneous exfoliation of greater than 30% total body surface area (%TBSA),
      increasingly being treated in burns centres. The rate of mortality varies
      significantly in the literature, with recent prospective studies in non-burns
      centres reporting percentage mortality of approximately 45%. We undertook a
      systematic review of published studies that included TEN patients treated
      specifically in burns centres to determine a cumulative mortality rate. METHODS:
      Electronic searches of MEDLINE, EMBASE and The Cochrane Library (Issue 4, 2010)
      databases from 1966 onwards were used to identify English articles related to the
      treatment of TEN in burns centres. RESULTS: The systematic literature search
      identified 20 studies which specifically described patients with TEN grater than
      30% %TBSA. Treatment regimens varied amongst studies, as did mortality. The
      overall percentage mortality of the combined populations was 30%. Risk factors
      commonly described as associated with mortality included age, %TBSA and delay to
      definitive treatment. CONCLUSION: The review highlights the variation between
      principles of treatment and mortality amongst burns centres. It offers a standard
      that burns centre can use to internationally compare their mortality rates. The
      review supports the ongoing reporting of outcomes in TEN patients with epidermal
      detachment greater than 30%.

PMID- 24685066
TI  - Use of a pediatric oxygenator integrated in a veno-venous hemofiltration circuit
      to remove CO2: a case report in a severe burn patient with refractory
      hypercapnia.
AB  - Acute respiratory distress syndrome management is currently based on lung
      protective ventilation. Such strategy may lead to hypercapnic acidosis. We report
      a case of refractory hypercapnia in a severe burn adult, treated with simplified
      veno-venous extracorporeal carbon dioxide removal technique. We integrated a
      pediatric oxygenator in a continuous veno-venous hemofiltration circuit. This
      technique, used during at least 96h, was feasible, sure and efficient with carbon
      dioxide removal rate up to 32%. 

PMID- 24685067
TI  - Safety and efficacy of excision and direct closure in acute burns surgery:
      outcome analysis in a prospective series of 100 patients and a survey of UK burns
      surgeons' attitudes.
AB  - Many burns surgeons avoid excision and direct closure of acute burns owing to
      concerns over wound dehiscence, scarring and infection. There is no evidence in
      the literature to support this practice. We present outcomes of a prospective
      series of 100 patients who underwent excision and direct closure of 138 burns
      over a 2-year period, along with results from a survey sent to 33 senior burns
      surgeons to gauge attitudes towards direct closure in burns surgery. 47% of
      survey respondents never perform direct closure. Dehiscence was cited as the most
      common concern, followed by hypertrophic scarring (HTS). In our cohort, the
      superficial dehiscence rate was 12% and the HTS rate was 16%, with no scarring
      contractures. Patients with healing time greater than 14 days were more likely to
      develop HTS (p=0.008), as were those with wound dehiscence (p=0.014). Patients
      undergoing part-grafting in addition to direct closure took significantly longer
      to heal than those undergoing direct closure alone (p=0.0002), with the donor
      site or graft delaying healing in the majority. Excision and direct closure of
      acute burn wounds avoids donor site morbidity and has an acceptable complication
      rate. It is a safe and effective treatment for full thickness burns in selected
      cases. 

PMID- 24685068
TI  - Real-time vascular mechanosensation through ex vivo artery perfusion.
AB  - BACKGROUND: Cell-based perfusion studies have provided great insight into fluid
      sensing mechanisms, such as primary cilia in the renal and vascular systems.
      However, the intrinsic limitations of in vitro cell culture, such as the
      inability to reflect cellular organization within tissues, has distanced observed
      paradigms from possible clinical developments. Here we describe a protocol that
      applies ex vivo artery perfusion and calcium imaging to observe real-time
      cellular responses to fluid-shear stress. RESULTS: Through our ex vivo artery
      perfusion method, we were able to simulate physiological flow and initiate
      distinct fluid shear stress mechanosensory responses, as well as induced
      acetylcholine responses in mouse aortic tissue. The observed calcium profiles
      confirm results found through previous in vitro cell culture experiments. The
      overall procedure, including dissection, sample preparation and perfusion, takes
      around 3 hours to complete. CONCLUSION: Through our unique method, we are able to
      induce laminar flow within intact mouse aortic tissue and illicit subsequent
      cellular responses. This method of ex vivo artery perfusion provides the
      opportunity to bridge the novel findings of in vitro studies with subsequent
      physiological models of fluid-shear stress mechanosensation in vascular tissues.

PMID- 24685069
TI  - Posttraumatic amnesia and personality changes after severe traumatic brain
      injury: preliminary findings.

PMID- 24685070
TI  - Interpersonal behaviors and socioemotional interaction of medical students in a
      virtual clinical encounter.
AB  - BACKGROUND: The virtual clinical encounter (VCE) may function as an important
      support for medical students in or prior to clinical practice to train and ease
      communication and socioemotional interactions with patients. Few studies have
      however focused on the dynamics of interpersonal behaviors in clinical
      interviewing with a virtual patient (VP) and the affective responses evoked by
      such a learning experience. The study was designed to investigate the dynamics
      and congruence of interpersonal behaviors and socioemotional interaction
      exhibited during the learning experience in a VCE, and to evaluate which
      interaction design characteristics contribute most to the behavioral and
      affective engagement in medical students. METHODS: Thirty medical students (sixth
      semester) participated voluntarily in an exploratory observational study with a
      highly interactive VP case based on a trustworthy VP encounter with a natural and
      realistic dialogue interface. Students worked collaboratively in pairs. They were
      videotaped for further behavioral analysis and self-reported (in both a survey
      and an interview) their personal opinions, perceptions and attitudes about the
      VCE. A mixed methods approach was applied. RESULTS: All participants demonstrated
      an adequate, respectful and relevant clinical case management and to obtain
      psychosocial history. The collaborative workspace played its role and led to
      dynamic and engaged discussions fostering thus shared understanding. The results
      suggest that the VCE studied was perceived as a meaningful, intrinsically
      motivational and activating learning environment, and was found to socially and
      emotionally engage learners. We also found that VCEs have the potential to
      support the development of relevant and congruent interpersonal communication
      skills in trainees. CONCLUSIONS: By taking advantage of socioemotional
      interaction, VCEs promote not only critical reflection skills or strategy
      selection skills, but also to develop listening and nonverbal skills, induce self
      awareness and target coping behaviours. We believe that, if applied in early
      medical education, this learning approach may facilitate clinical encounters at
      an early stage and contribute to responsible clinical decision making.

PMID- 24685071
TI  - Factors affecting final facial nerve outcome following vestibular schwannoma
      surgery.
AB  - OBJECTIVE: To determine factors affecting facial nerve outcome of vestibular
      schwannoma surgery. METHODS: This retrospective cohort study comprised 652
      patients. The outcome measure was House-Brackmann classification at two years
      post-operatively. Univariate and multivariate analyses were carried out to
      determine the factors affecting facial nerve outcome. The incidence rates of
      hemifacial spasm, metallic taste and crocodile tear syndrome were recorded.
      RESULTS: For tumours less than 1.5 cm, 95 per cent of outcomes were normal, 100
      per cent were satisfactory (House-Brackmann grades I-III) and 0 per cent were
      unsatisfactory (grades IV-VI). For tumours 1.5-2.4 cm, 83 per cent of outcomes
      were normal, 99 per cent were satisfactory and 1 per cent were unsatisfactory.
      For tumours 2.5-3.4 cm, 68 per cent of outcomes were normal, 96 per cent were
      satisfactory and 4 per cent were unsatisfactory. For tumours 3.5-4.4 cm, 52 per
      cent of outcomes were normal, 80 per cent were satisfactory and 20 per cent were
      unsatisfactory. For tumours larger than 4.4 cm, 50 per cent of outcomes were
      normal, 72 per cent were satisfactory and 28 per cent were unsatisfactory.
      CONCLUSION: Tumour size and operation year were significant predictors of facial
      nerve outcome. The surgical learning curve was steepest for the first 50
      patients.

PMID- 24685073
TI  - Association between 1019C/T polymorphism in the connexin 37 gene and essential
      hypertension.
AB  - OBJECTIVE: To investigate the association between the CX 37 1019C/T polymorphism
      and the susceptibility to essential hypertension (EH). METHODS: A total of 1126
      cases of EH were diagnosed in the People's Hospital of Wuxi City, China. A
      control group consisted of 874 healthy people, i.e., non-EH patients. All cases
      were genotyped by DNA sequencing. RESULTS: Polymorphism C1019T on the Connexin37
      gene was found in the whole population. The distribution of three genotype
      frequencies in both groups was in accordance with the Hardy-Weinberg equilibrium.
      The frequency of the CX37C allele was higher in EH patients (57.4% vs. 42.1%,
      chi(2)=92.5, P<0.01) compared to the control group. The frequency of C carriers
      (CC+TC) was 80.5% in EH patients compared to 66.7% in the control (chi(2)=49.0,
      P<0.01). EH risk was significantly increased in carriers of C the allele (CC+TC)
      over that in the TT homozygote (OR=2.06, 95% CI: 1.68 ~ 2.52). Subsequent
      stratified analyses demonstrate that a significant difference exists in the
      frequency of C carriers between male EH patients and controls (79.2% vs. 69.1%,
      chi(2)=13.4, P<0.01) and in female EH patients and the control group (81.8% vs.
      64.4%, chi(2)=38.7, P<0.01). The carriers of the C allele had higher EH risk
      compared with the TT homozygote without sex differences (male: OR=1.71, 95% CI:
      1.28 ~ 2.27; female: OR=2.48, 95%CI: 1.85 ~ 3.31). CONCLUSION: The C allele in
      the CX37 gene might be associated with the susceptibility to EH in population of
      Wuxi, China.

PMID- 24685072
TI  - Antenatal telephone support intervention with and without uterine artery Doppler
      screening for low risk nulliparous women: a randomised controlled trial.
AB  - BACKGROUND: The number of routine antenatal visits provided to low risk
      nulliparous women has been reduced in the UK, acknowledging this change in care
      may result in women being less satisfied with their care and having poorer
      psychosocial outcomes. The primary aim of the study was to investigate whether
      the provision of proactive telephone support intervention (TSI) with and without
      uterine artery Doppler screening (UADS) would reduce the total number of
      antenatal visits required. A secondary aim was to investigate whether the
      interventions affected psychological outcomes. METHODS: A three-arm randomised
      controlled trial involving 840 low risk nulliparous women was conducted at a
      large maternity unit in North East England. All women received antenatal care in
      line with current UK guidance. Women in the TSI group (T) received calls from a
      midwife at 28, 33 and 36 weeks and women in the telephone and Doppler group (T +
      D) received the TSI and additional UADS at 20 weeks' gestation. The main outcome
      measure was the total number of scheduled and unscheduled antenatal visits
      received after 20 weeks' gestation. RESULTS: The median number of unscheduled (n
      = 2.0), scheduled visits (n = 7.0) and mean number of total visits (n = 8.8) were
      similar in the three groups. The majority (67%) of additional antenatal visits
      were made to a Maternity Assessment Unit because of commonly occurring pregnancy
      complications. Additional TSI+/-UADS was not associated with differences in
      clinical outcomes, levels of anxiety, social support or satisfaction with care.
      There were challenges to the successful delivery of the telephone support
      intervention; 59% of women were contacted at 29 and 33 weeks gestation reducing
      to 52% of women at 37 weeks. CONCLUSIONS: Provision of additional telephone
      support (with or without UADS) in low risk nulliparous women did not reduce the
      number of unscheduled antenatal visits or reduce anxiety. This study provides a
      useful insight into the reasons why this client group attend for unscheduled
      visits. TRIAL REGISTRATION: ISRCTN62354584.

PMID- 24685074
TI  - Erythropoietin modulates imbalance of matrix metalloproteinase-2 and tissue
      inhibitor of metalloproteinase-2 in doxorubicin-induced cardiotoxicity.
AB  - BACKGROUND: Doxorubicin (DOX) is a highly effective anti-cancer drug with limited
      clinical use due to its serious cardiotoxicity. Recent studies reported that
      erythropoietin (EPO) could exert a cardioprotective effect by non-erythropoietic
      effects. This study was to investigate fibrosis of DOX-induced cardiotoxicity and
      determine mechanisms of EPO against extracellular matrix (ECM) remodelling.
      METHODS: Rats were grouped as the control group, the DOX group and the DOX+EPO
      group. DOX (2.5 mg/kg/dose, six doses for two weeks) was administered to induce
      cardiotoxicity by intraperitoneal injections in the DOX group and the DOX+EPO
      group, and EPO (2500U/kg/dose, six doses for two weeks) was administered
      simultaneously in the DOX+EPO group. Two weeks after the last administration,
      rats were killed with cardiac tissues used for histological analyses and
      immunological detections for matrix metalloproteinase-2 (MMP-2) and tissue
      inhibitor of metalloproteinase-2 (TIMP-2). RESULTS: Rats treated with DOX showed
      degenerative changes with cardiac fibrosis. Compared to the control group, the
      expression of MMP-2 was up-regulated whereas that of TIMP-2 was down-regulated in
      the DOX group. EPO administration improved cardiac fibrosis, decreased MMP-2
      expression, increased TIMP-2 expression and ameliorated imbalance of MMP-2/TIMP-2
      ratio. CONCLUSIONS: The present study suggests that EPO can exert a
      cardioprotective effect on DOX-induced cardiotoxicity which may be associated
      with improving MMP-2/TIMP-2 imbalance.

PMID- 24685075
TI  - Prevalence of venous thromboembolic events and diagnostic performance of the
      wells score and revised geneva scores for pulmonary embolism in patients with
      interstitial lung disease: a prospective study.
AB  - BACKGROUND: To determine the prevalence of venous thromboembolism (VTE) in
      patients with connective tissue disease-related interstitial lung diseases (CTD
      ILD) and idiopathic interstitial pneumonia (IIP) and to further evaluate
      associated risk factors. To also examine the diagnostic performance of the Wells
      score and the revised Geneva scores for diagnosing pulmonary embolism (PE) in ILD
      patients. METHOD: Fifty-seven patients with CTD-ILD and IIP were prospectively
      enrolled. Plasma D-dimer was measured by ELISA. Deep-vein thrombosis (DVT) was
      examined by venous ultrasonography and PE by computed tomography pulmonary
      angiography. PE prevalence was further assessed by the Wells score and the
      revised Geneva score. RESULTS: VTE was diagnosed in 15 (26.3%, 15/57) patients.
      Bivariate analysis revealed that dyspnoea (OR 3.750, 95%CI 1.095-12.842,
      P=0.035), lower extremity oedema (OR 8.667, 95%CI1.814-41.408, P=0.007),
      palpitations (OR 4.75, 95%CI1.073-21.032, P=0.040), and positive D-dimer (OR
      5.087, 95%CI 1.015-25.485, P=0.048) were associated with VTE. Using the Wells
      Score, 46 (80.70%), eight (14.4%) and three (5.26%) patients had a low,
      intermediate and high probability of PE, respectively, with seven (15.22%), three
      (37.5%) and two (66.67%) of the respective cases confirmed. By the revised Geneva
      score, 23 (40.35%), 32 (56.14%) and two (3.51%) patients had a low, intermediate
      and high probability of PE, respectively, with two (8.70%), nine (28.13%) and one
      (50.00%) of the respective cases confirmed. The AUC for the Wells score and the
      revised Geneva score was 0.720+/-0.083 (CI 0.586 to 0.831) and 0.704+/- 0.081 (CI
      0.568 to 0.817), respectively. CONCLUSION: VTE can be seen in approximately one
      fourth of patients with CTD-ILD or IIP and the Wells score and the revised Geneva
      score can be used for categorising PE risk.

PMID- 24685077
TI  - [To follow the past and herald the future, and create new wonders].

PMID- 24685076
TI  - Radiation exposure with the radial approach for diagnostic coronary angiography
      in a centre previously performing purely the femoral approach.
AB  - INTRODUCTION: Use of the radial approach for coronary angiography and
      percutaneous coronary intervention (PCI) is known to improve many patient outcome
      measures. However, there is some concern that it may be associated with increased
      patient radiation exposure. This study explores radiation exposure with the
      radial approach compared with the femoral approach in a centre previously
      performing purely femoral approach. PATIENTS AND METHODS: Data was collected
      retrospectively for all patients undergoing diagnostic coronary angiography over
      a six month period. PCIs and procedures with inherent technical difficulty or use
      of additional techniques (graft studies, optical coherence tomography, fractional
      flow reserve) were excluded. Dose area product (DAP) and fluoroscopy time (FT)
      were analysed for all remaining procedures (n=389), comparing radial (n=109) and
      femoral (n=280) approaches. RESULTS: The overall mean FT for transradial cases
      (7.45 mins) was significantly higher than for transfemoral cases (4.59 mins;
      p<0.001). The overall mean DAP for transradial cases (95.64 G Gycm(2)) was
      significantly higher than for transfemoral cases (70.25 Gycm(2), p<0.05)).
      Neither the FT nor the DAP decreased over the six month period. CONCLUSION: The
      radial approach was associated with significantly higher DAP and FT compared to
      the femoral approach during an initial introductory phase which was likely
      insufficient to develop radial proficiency. The results of this study are
      consistent with previous studies and may influence choice of access for non
      emergent diagnostic coronary angiography before radial proficiency has been
      established, particularly for patients more susceptible to radiation risks.

PMID- 24685078
TI  - [Laparoscopic surgery could be considered as routine treatment for elderly
      patients with colorectal cancer].

PMID- 24685079
TI  - [Effects of dioscin on apoptosis in pancreatic cancer MiaPaCa-2 cells and its
      mechanism].
AB  - OBJECTIVE: The aim of this study was to observe the effects of dioscin on
      apoptosis and on expression of PRDX1 in pancreatic cancer MiaPaCa-2 cells in
      vitro. METHODS: MTT assay was used to detect the growth rate among the medication
      groups treated with different concentrations of dioscin. The apoptosis rate was
      determined by annexin V-fluorescein isothiocyanate/propidium iodide double
      staining and flow cytometry. Western blot analysis was used to assay the
      expression of PRDX1 and apoptotic proteins in the cells. Reactive oxygen species
      (ROS) formation was measured by 2'7'-dichlorofluorescein diacetate (DCFH-DA).
      RESULTS: Dioscin considerably inhibited the proliferation of MiaPaCa-2 cells in
      vitro. The inhibitory action was enhanced in a dose-dependent manner. The levels
      of intracellular ROS detected with DCFH-DA were highly increased after dioscin
      treatment. The flow cytometry analysis using annexin V-PI staining showed that
      compared with the apoptotic rate of control group [(3.5 +/- 0.7)%], 2.5 umol/L
      and 5 umol/L dioscin induced apoptosis in (28.4 +/- 0.9)% and (49.6 +/- 2.7)%
      MiaPaCa-2 cells, and Western blot analysis showed that apoptotic proteins Bax and
      cleaved caspase-3 expressions were increased and antiapoptotic protein Bcl-2
      expression was decreased. In addition, these effects could be blocked by
      antioxidant N-acetylcysteine (NAC) administration, and the apoptotic rates
      decreased to (10.8 +/- 2.3)% and (18.8 +/- 3.0)%, respectively. We further
      observed the decrease of PRDX1 expression after dioscin treatment. Moreover,
      after PRDX1 overexpression, dioscin treatment no longer induced high levels of
      ROS and apoptosis, and the apoptotic rate was decreased to (21.3 +/- 5.9)%.
      CONCLUSION: Dioscin can down-regulate the PRDX1 expression, and then induces ROS
      mediated apoptosis in cancer cells.

PMID- 24685080
TI  - [Targeted Sox4 gene-knock-down suppresses xenograft growth of Xuanwei female lung
      cancer cell line XWLC-05 cells in nude mice].
AB  - OBJECTIVE: To study the effect of targeted Sox4 gene-knock-down on the growth of
      xenografts of Xuanwei female lung cancer cell line XWLC-05 cells in nude mice.
      METHODS: Recombinant plasmid pGFP-V-RS-Sox4 shRNA was constructed and transfected
      into XWLC-05 cells. Real-time quantitative PCR and Western blot were applied to
      confirm the effect of Sox4 gene-knock-down. XWLC-05 cells stably transfected with
      the plasmids were inoculated into nude mice to establish the xenograft model. The
      nude mouse status, tumor formation and tumor growth were observed, and the tumor
      inhibition rate was calculated. CT scan was performed to assess the metastasis of
      xenografts. Immunohistochemical staining was applied to detect Sox4 and ki-67
      protein expression. RESULTS: Recombinant plasmid pGFP-V-RS-A-Sox4 shRNA which can
      effectively knocking-down Sox4 gene was successfully constructed and the stable
      transfected cells were selected by puromycin-screening. The success rate of tumor
      cell inoculation was 100% in the mice of all groups except those inoculated with
      saline. The body weight of all mice inoculated with parental XWLC-05 cells (blank
      control), pGFP-V-RS-scram shRNA trsfected XWLC-05 cells (negative control), and
      pGFP-V-RS-Sox4 shRNA transfected XWLC-05 cells was increased to a varying degree,
      but there was no significant difference among the groups (P > 0.05 ). The growth
      of xenografts was significantly inhibited after silencing the Sox4 gene
      expression when compared with that of the blank and negative controls (P < 0.05)
      . The volume of removed tumors of the Sox4 gene-inhibited mice was (2.30 +/-
      0.34) cm(3) , significantly smaller than that of the negative control (3.99 +/-
      0.45) cm(3) and the blank control (4.03 +/- 0.42) cm(3) (P < 0.05) . The weight
      of removed tumors of Sox4 gene-inhibited mice was (0.86 +/- 0.14) g,
      significantly lower than that of the negative control (1.84 +/- 0.27) g and blank
      control (1.86 +/- 0.22) g, (P < 0.05). Immunohistochemical staining showed that
      Sox4 and ki-67 proteins mainly expressed in cell nuclei. The staining was
      significantly decreased in xenografts of Sox4-inhibited mice when compared with
      the negative and blank controls (P < 0.05). No distant metastasis was found in
      any mouse by CT imaging and pathological examination during the observation
      period. CONCLUSIONS: The xenograft model of Xuanwei female lung cancer cell line
      XWLC-05 cells in nude mice is successfully established. Knocking-down of Sox4
      gene can suppress the xenograft tumor growth.

PMID- 24685081
TI  - [Enrichment and functional characterization of cancer stem cells from squamous
      cell carcinoma of head and neck by suspension culture].
AB  - OBJECTIVE: Initiation, growth, recurrence, and metastasis of head and neck
      squamous cell carcinoma (HNSCC) have been related to the cancer stem cells (CSC)
      that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH-1)
      activity. In this study, we try to prove that suspension culture can enrich ALDH
      1 high expression cells within HNSCC cell lines and the enriched cells possess
      cancer stem cell properties. METHODS: Cells from five HNSCC cell lines were
      cultured in ultra-low attachment plates in serum-free Quantum 263 medium
      supplemented with 10 ng/ml EGF and 10 ng/ml bFGF, and ALDH-1 expression level was
      evaluated by ALDEFLUOR assay. ALDH-1 high expression cells were separated by FACS
      sorting, and their phenotypical and functional properties were characterized.
      RESULTS: Spheroids can be formed from all five HNSCC cell lines (UD-SCC1, UT
      SCC22, UM-SCC11B, UT-SCC9 and UT-SCC24A) under anchorage independent culture
      condition. The proportion of ALDH1 high expression cells were highly increased in
      speroids derived cells (SDCs) compared with their monolayers (P < 0.05). The
      clones formed by ALDH1 high expression cells on average contained 197 (197 +/-
      47) cells compared with 33 (33 +/- 16) cells in clones generated from ALDH1 low
      expression cells (P < 0.01). Single ALDH1 high expression cell could
      significantly better regenerate a spheroid (UT-SCC9: 17.1%, UD-SCC1:19.3%),
      whereas under the same conditions single ALDH1 low expression cells regenerated
      only in one case a spheroid (P < 0.01). SDCs from all five tested cell lines also
      showed a significantly increased invasion capacity (P < 0.05). We also found that
      the mRNA levels of Oct-4, Sox2, and Nanog were all significantly increased in the
      SDC. The reactive oxygen species (ROS) levels in SDCs from UD-SCC1 and UT-SCC24A
      were significantly increased compared with their monolayer counterpart [(26.3 +/-
      4.9)% vs (8.6 +/- 1.7)% and (72.1 +/- 6.1)% vs (23.7 +/- 7.5)%, P < 0.05)].
      CONCLUSION: Cancer stem cells can be enriched by suspension culture, which may be
      of importance in investigation of their contribution to therapy resistance, tumor
      recurrence and metastasis.

PMID- 24685082
TI  - [Relationship between human papilloma virus infection and expression of p16 and
      EGFR in head and neck squamous cell carcinoma and their prognostic significance].
AB  - OBJECTIVE: To detect the infection of human papillomavirus (HPV) 6/11, 16/18,
      31/33 in patients with head and neck squamous cell carcinoma and explore the
      relationship between HPV infection and expression of p16 and EGFR in the tumor
      tissue and their clinical significance. METHODS: The infection of HPV6/11, 16/18,
      31/33 was detected by in situ hybridization (ISH), and expression of p16 and EGFR
      was assessed by immunohistochemistry in biopsy or surgical specimens of 43 cases
      of head and neck squamous cell carcinoma, and analyzed its impact on the
      prognosis. Spearman rank correlation method was used for analysis of the
      relationship. Overall survival rate of the patients was estimated by Kaplan-Meier
      analysis. Cox regression model was used for multivariate analysis. RESULTS:
      HPV6/11, 16/18, 31/33 were detected in 25.6% (11/43) of this group of patients,
      among them, HPV16/18 accounted for 63.6%, HPV31/33 accounted for 27.3%, and
      HPV6/11 accounted for 0. EGFR was expressed in 69.8% and p16 was expressed in
      53.5% of the patients. The difference was statistically significant between the
      HPV-positive and HPV-negative groups in ethnicity, smoking, alcohol consumption
      (P = 0.045, 0.040, 0.011, respectively). HPV infection was found to be positively
      correlated with p16 expression and inversely correlated with EGFR expression (P =
      0.029, P = 0.009). The expression of p16 protein was negatively correlated with
      EGFR protein expression (r = -0.447, P = 0.003). The 3-year overall survival rate
      was 60.0% in the HPV-positive group and 59.7% in the negative group (P = 0.789);
      72.2% in the p16-positive patients and 43.9% in the p16-negative patients (P =
      0.012); 48.8% in the EGFR-positive patients and 81.8% in the EGFR-negative
      patients (P = 0.037). CONCLUSIONS: The results of our study suggest that the HPV
      infection rate, HPV subtypes and clinicopathological features of HPV-positive
      SCCHN are in accordance with those reported in Western literatures. There may be
      differences between the HPV infections in Uygur and Han nationalities. HPV
      infection is positively correlated with p16 and negatively correlated with EGFR
      expressions. The prognosis of p16-positive patients is significantly better than
      that of negative cases, and p16 is an independent prognostic factor for head and
      neck squamous cell carcinoma.

PMID- 24685083
TI  - [Impact of histology on efficacy of pemetrexed: pemetrexed in second-line setting
      and as maintenance therapy after first-line treatment in Chinese patients with
      advanced NSCLC].
AB  - OBJECTIVE: To evaluate the impact of histology on efficacy of pemetrexed in
      Chinese non-small cell lung cancer (NSCLC) patients. This report summarized the
      results of two clinical trials of pemetrexed in Chinese patients with advanced
      NSCLC in 2nd line setting and maintenance setting after 1st line (JMID study and
      Chinese subgroup from JMEN study) treatment. METHODS: For the Chinese JMID study
      (second-line), Chinese patients with locally advanced or metastatic (stage IIIA,
      IIIB or IV) NSCLC who had prior chemotherapy were enrolled. The study was
      designed to investigate the noninferiority of pemetrexed (500 mg/m(2), day 1 of
      each 21-day cycle) to docetaxel (75 mg/m(2), day 1 of each 21-day cycle) in terms
      of overall survival (OS). For the global JMEN study (maintenance), patients
      initially diagnosed with IIIB or IV NSCLC, those who had not progressed after
      completing at least four cycles of platinum-based chemotherapy were enrolled to
      test for the superiority of pemetrexed (500 mg/m(2), day 1 of each 21-day cycle)
      over placebo with progression free survival (PFS) as primary endpoint. RESULTS:
      In JMID study, the OS was similar between the pemetrexed group (Pem group) and
      docetaxel group (Doc group). Retrospective histological subtype analysis showed
      survival benefits (both OS and PFS) numerically of non-squamous patients over
      squamous patients in the Pem group (OS: HR 0.74, 95% CI 0.45-1.21, P = 0.2267,
      median 11.7 vs. 9.7 months; PFS: HR 0.77, 95% CI 0.44-1.34, P = 0.3585, median
      3.0 vs. 1.7 months). In the Chinese subgroup of JMEN study, the median PFS in the
      Pem group for squamous and nonsquamous patients was 4.2 and 1.5 months for
      squamous patients, the median OS in the Pem group for squamous and nonsquamous
      patients was 22.5 and 6.2 months for squamous patients. In JMEN China subgroup
      analysis, the HR on histology was not analyzed due to the small sample size. In
      terms of safety profile, drug-related grade 3 or 4 hematological toxicities
      (leukocytopenia and neutropenia) events occurring after second-line treatment
      were significantly lower in the Pem group than in the Doc group (both P < 0.001).
      Similarly in patients receiving pemetrexed maintenance after first-line
      treatment, incidences of toxicity events were low. CONCLUSIONS: Consistent with
      global results, in Chinese NSCLC patients, histology has an impact on the
      efficacy of pemetrexed, in which non-squamous histology predicts a positive
      outcome for patients treated with pemetrexed. In terms of overall safety,
      pemetrexed is better than docetaxel with a lower incidence of adverse events and
      anticipates manageable safety profile in NSCLC patients. Based on consistent
      Chinese data from the two studies, pemetrexed is recommended as a standard
      chemotherapy regime in both second-line and maintenance setting after first-line
      treatment for Chinese non-squamous NSCLC patients.

PMID- 24685084
TI  - [4D-CT-based plan target volume (PTV) definition compared with conventional PTV
      definition using general margin in radiotherapy for lung cancer].
AB  - OBJECTIVE: To investigate the dosimetric benefit of 4D-CT in the planning target
      volume (PTV) definition process compared with conventional PTV definition using
      general margin in radiotherapy of lung cancer. METHODS: A set of 4D-CT images and
      multiphase helical CT scans were obtained in 10 patients with lung cancer. The
      radiotherapeutic plans based on PTV determined by 4D-CT and in addition of
      general margin were performed, respectively. The 3D motion of the centroid of GTV
      and the 3D spatial motion vectors were calculated. The differences of the two
      kinds of PTVs, mean lung dose (MLD), V5,V10,V15,V20 of total lung, mean heart
      dose (MHD), V30 and V40 of heart, D99 and D95 were compared, and the correlation
      between them and the 3D spatial motion vector was analyzed. RESULTS: The PTV4D in
      eight patients were smaller than PTVconv, with a mean reduction of (13.0 +/-
      8.0)% (P = 0.018). In other two patients, whose respiration motion was great,
      PTV4D was larger than PTVconv. The mean 3D spatial motion vector of GTV centroid
      was (0.78 +/- 0.72)cm. By using 4D-CT, the mean reduction of MLD was (8.6 +/-
      9.9)% (P = 0.037). V5, V10, V15, V20 of total lung were decreased averagely by
      (7.2 +/- 10.5)%, (5.5 +/- 8.9)%, (6.5 +/- 8.4)% and (5.7 +/- 7.4)%, respectively
      (P < 0.05 for all). There was a significant positive correlation between
      PTV4D/PTVconv and the 3D spatial motion vector of the GTV centroid (P = 0.008). A
      significant inverse correlation was found between D994D/D99conv and the 3D
      spatial motion vector of the GTV centroid (P = 0.002). D994D/D99conv, (MLDconv
      MLD4D) /MLDconv, total lung (V5conv-V54D)/V5conv, total lung (V10conv
      V104D)/V10conv, (MHDconv-MHD4D)/MHDconv, heart (V30conv-V304D)/V30conv were
      inversely correlated with PTV4D/PTVconv (P < 0.05 for all). CONCLUSIONS: 4D-CT
      can be used to evaluate the respiration motion of lung tumor accurately. The 4D
      CT-based PTV definition and radiotherapeutic planing can reduce the volume of PTV
      in patients with small respiration motion, increase the intra-target dose, and
      decrease the dose of normal tissue sequentially. For patients with large
      respiration motion, especially those more than 1.5-2 cm, this method can avoid
      target miss, meanwhile, not increase the dose of normal tissue significantly.

PMID- 24685085
TI  - [Prophylactic use of low molecular weight heparin in combination with graduated
      compression stockings in post-operative patients with gynecologic cancer].
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of low molecular
      weight heparin (LMWH) combined with graduated compression stockings (GCS) with
      GCS alone as prophylactic measures for venous thromboembolism (VTE) in post
      operative patients with gynecologic cancer. METHODS: Patients diagnosed with
      gynecologic cancer undergoing primary major surgery between 2010 and 2011 in our
      institute were randomized to receive LMWH+GCS or GCS as VTE prophylaxis post
      operatively. RESULTS: Altogether 247 patients were enrolled. The incidence of VTE
      in patients treated with LMWH + GCS was significantly lower than that in patients
      using GCS alone (0.8% Vs. 8.1%, P = 0.01). There were no severe bleeding
      complications in the patients with prophylactic use of LMWH and the occurrence
      rate of wound dehiscence was comparable between the two groups (P > 0.05).
      Multivariable logistic regression analysis revealed that age over 60 years (P =
      0.015) , duration of operation over 3 hours (P = 0.04) and without prophylactic
      use of LMWH (P = 0.02) were independent risk factors for VTE. CONCLUSIONS: Dual
      prophylaxis with LMWH and GCS should be recommended for gynecologic cancer
      patients undergoing major surgery for its better efficacy than GCS. Prophylactic
      use of LMWH is safe and convenient. Patients with older age and prolonged
      operation time are at highest risk of developing VTE post-operatively.

PMID- 24685086
TI  - [Evaluation of the rationality of current T staging of gastric cancer with
      transverse mesocolon invasion].
AB  - OBJECTIVE: To evaluate the rationality of T staging of gastric cancer with
      transverse mesocolon invasion. METHODS: Data of 808 patients with primary gastric
      cancer undergoing surgical treatment was screened from the Data base of Gastric
      Cancer of Sun Yat-sen University, from April 1996 to October 2009. According to
      the information of transverse mesocolon invasion, all cases were divided into
      groups NOI (T4a stage, non organ invasion, n = 638), NTMI (T4b stage, non
      transverse mesolon invasion, with organ invasion, n = 126), and TMI (transverse
      mesocolon invasion, n = 44). The clinicopathological features, surgical procedure
      and prognosis were compared among the three groups. RESULTS: No significant
      difference was found in gender, age, lymph node metastasis, hepatic metastasis,
      tumor's Borrmann type, histological type, differentiation degree, value of serum
      CEA among the 3 groups (all P > 0.05). In the groups NOI, NTMI and TMI, the ratio
      of mean tumor diameter >= 5 cm was 39.0% (249/638), 61.1% (77/126) and 54.5%
      (24/44), respectively; the ratio of distal metastasis was 11.9% (76/638), 30.2%
      (38/126) and 43.2% (19/44), respectively; the ratio of peritoneal metastasis was
      8.2% (52/638), 26.2% (33/126) and 38.6% (17/44), respectively; the ratio of TNM
      IV stage was 25.4% (162/638), 84.7% (107/126) and 93.7% (41/44), respectively;
      and the ratio of radical resection was 92.0% (587/638), 69.8% (88/126) and 77.3%
      (34/44), respectively; all with significant differences (P < 0.01), and the
      results of pairwise comparisons (Bonferroni correction, significant level alpha =
      0.05/3 = 0.0167) showed that these parameters were significantly different
      between groups NOI and TMI (P < 0.0167), but non-significant between groups NTMI
      and TMI (P > 0.0167). The median survival time was 42.0, 16.4 and 19.0 months in
      the groups NOI, NTMI and TMI, respectively (P < 0.01), and the results of
      pairwise comparison showed that the prognosis were significant different between
      the groups NOI and TMI (P < 0.01), but non-significant between the groups NTMI
      and TMI (P > 0.05). In the cases who received radical resection, the median
      survival time was 47.9, 23.5 and 21.4 months in the groups NOI, NTMI and TMI,
      respectively (P < 0.01), and the results of pairwise comparison showed that the
      prognosis was significantly different between the groups NOI and TMI (P < 0.05),
      but not significant between groups NTMI and TMI (P > 0.05). CONCLUSIONS: The
      tumor size, distal meatastasis, peritoneal metastasis, TNM stage, surgical
      procedure and prognosis of gastric cancer with transverse mesocolon invasion are
      similar to that of T4b gastric cancer, but are significantly different from that
      of T4a gastric cancer. Gastric cancer with transverse mesocolon invasion should
      be reclassified as T4b stage.

PMID- 24685087
TI  - [(99)Tc(m)N-NOET dual-phase SPECT in differential diagnosis of benign and
      malignant lung tumors].
AB  - OBJECTIVE: To investigate the value of (99)Tc(m)N-NOET dual-phase SPECT in
      differential diagnosis of benign and malignant lung tumors. METHODS: CT scan,
      early (20 to 30 min) and delayed (2 h) imaging of NOET SPECT were performed on 61
      patients suspected of lung lesions before operation. The results were compared
      with the pathological findings. All cases were not treated with radiotherapy,
      chemotherapy or surgery before checks. Moreover, all patients had pathological
      diagnosis. To determine the value in differential diagnosis of tumors by
      analyzing the tumor uptake and excretion of (99)Tc(m)N-NOET, and the results were
      compared with that of CT. RESULTS: The value of early T/N ratio (ER) in the
      malignant (G1) and benign (G2) groups was 1.25 +/- 0.15 and 1.09 +/- 0.11 (P <
      0.001), respectively, and delayed T/N ratio (DR) was 1.40 +/- 0.17 and 1.18 +/-
      0.21 (P < 0.001). The retention index (RI) of groups G1 was (12.22 +/- 6.38)% and
      group G2 was (8.3 +/- 10.91)%, with a non-significant difference between them (P
      > 0.05). The ER, DR and RI of NOET SPECT in the malignant patients were not
      significantly correlated with TNM staging, pathological types, tumor diameter,
      cavity in the lung tumor mass, history of smoking, tumor size and patient gender
      (P > 0.05). The sensitivity of NOET dual-phase SPECT and CT in the differential
      diagnosis of benign and malignant lung tumors was 94.1% vs. 90.2%, specificity
      was 70.0% vs. 80.0% , positive predictive value (PPV) was 94.1% vs. 95.8%,
      negative predictive value (NPV) was 70.0% vs. 61.5 %, and accuracy was 90.2%. vs.
      88.5% (P > 0.05 for all). CONCLUSIONS: (99)Tc(m)N- NOET dual-phase SPECT could be
      used in differential diagnosis of benign and malignant lung tumors, with no
      significant differences compared with the efficacy of CT imaging. The
      semiquantitative indexes (ER, DR and RI) of NOET SPECT can also be used in
      differential diagnosis of benign and malignant lung tumors, and are not
      significantly correlated with TNM staging, pathological types, tumor diameter,
      cavity of the lung tumor mass, history of smoking, tumor size and patient gender.

PMID- 24685088
TI  - [Role of conventional pulmonary function tests and stair climbing test in the
      prediction of postoperative cardiopulmonary complications in non-small cell lung
      cancer patients after surgery].
AB  - OBJECTIVE: To evaluate and compare the value of stair climbing tests and
      conventional pulmonary function tests in the prediction of postoperative
      cardiopulmonary complications in non-small cell lung cancer patients underwent
      surgery. METHODS: From April 1, 2010 to Jan. 30, 2012, a total of 162 patients
      with thoracic carcinoma underwent stair climbing test (SCT) and conventional
      pulmonary function tests (PFT) preoperatively. The correlation of postoperative
      cardiopulmonary complications with the SCT and PFT parameters were analyzed
      retrospectively using chi-square test, independent sample t test and binary
      logistic regression analysis. RESULTS: Of the 162 patients, 19 without operation
      were excluded, due to an advanced stage (9 cases), poor cardiopulmonary function
      (5 cases), rejecting operation (4 cases) and exploration alone (1 case). 143
      cases were eligible and evaluated eventually. Forty-one of the 143 patients
      (28.7%) had postoperative cardiopulmonary complications, but no death occurred.
      The patients were stratified into groups based on the time of stair climbing 5
      stories (18.36 m, t, <92 s, >= 92 s). Exercise oxygen desaturation (EOD) during
      the stair climbing test (<5%, >= 5%) and the difference between the pulse at
      resting state and the pulse at end of stair climbing test (DeltaP, <55 beats/min,
      >= 55 beats/min), respectively. The rate of postoperative cardiopulmonary
      complications was significantly higher in the group with t >= 92 s, EOD >= 5% and
      DeltaP < 55 beats/min (38.5%, 42.0% and 35.1%, respectively) than that in the
      group with t<92 s, EOD<5% and DeltaP >= 55 beats/min (16.9%, 21.5% and 18.2%,
      respectively). Binary logistic regression analysis showed that postoperative
      cardiopulmonary complications were independently correlated with EOD and lung
      function which did not meet the requirement of the lung resection operation mode.
      CONCLUSIONS: A symptom-limited stair climbing test is a safe, simple and low-cost
      method to evaluate the cardiopulmonary function preoperatively. It can predict
      the occurrence of postoperative cardiopulmonary complications in non-small cell
      lung cancer patients. Conventional pulmonary function tests and stair-climbing
      test can be recommended to be routinely performed in all patients with non-small
      cell lung cancer before thoracic surgery.

PMID- 24685089
TI  - [Analysis of efficacy and prognostic factors of transarterial chemoembolization
      combined with multimodality therapy for huge hepatocellular carcinoma].
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy, survival and
      prognosis of transarterial chemoembolization (TACE) alone and TACE in combination
      with multimodality therapy for huge hepatocellular carcinoma. METHODS: A
      retrospective analysis was conducted in 115 patients with huge hepatocellular
      carcinoma treated in our hospital from August 2008 to January 2012. Among them,
      72 patients were treated by TACE alone (TACE group) and 43 patients by TACE plus
      multimodality therapy (TACE-combined treatment group). Their clinicopathological
      data and survival were analyzed. RESULTS: The median follow-up of the 115 cases
      was 24 months (range 1-40 months). The 1-, 2-, and 3-year overall survival (OS)
      rates for the TACE group were 60.4,% 23.3% and 9.8%, respectively, and 39 months,
      78.1%, 43.3% and 36.8%, respectively, for the combined treatment group (P <
      0.001). The univariate analysis showed that the patient gender and age, HIV
      infection and AFP level were not significantly correlated with prognosis of the
      patients (P > 0.05 for all), while multimodality therapy, Child's grading, ECOG
      scores, distant metastasis, and portal vein tumor thrombus were significantly
      related to the overall survival. Moreover, the Cox multivariate survival analysis
      revealed that therapy and ECOG scores were independent prognostic indicators (P <
      0.05 for all). CONCLUSIONS: Multimodality therapy is a safe and effective
      treatment for huge hepatocellular carcinoma. Multimodality therapy and ECOG
      scores are independent prognostic indicators for the patients.

PMID- 24685090
TI  - [Application of laparoscopy in the modified nerve plane-sparing radical
      hysterectomy of cervical cancer].
AB  - OBJECTIVE: The aim of this study was to assess the feasibility and safety of
      laparoscopic nerve plane-sparing radical hysterectomy (NPSRH) and compare with
      that of open NPSRH. METHODS: One hundred and thirty-four patients with FIGO stage
      Ib1-IIa2 cervical cancer were enrolled in the study. Thirty-three patients
      underwent laparoscopic NPSRH. During the operation, the pelvic autonomic nerve
      plane which is directly underneath the ureter was integrally preserved by
      dissecting the pelvic spaces laparoscopically. The vessels around the nerve plane
      were controlled by Hem-o-lok polymer clips. One hundred and one patients
      underwent open NPSRH without special instruments. The clinical, pathological and
      surgery-related parameters were compared between the two groups. Moreover,
      postoperative short-term bladder function of these patients was also analyzed.
      RESULTS: There was no significant difference between the laparoscopic group and
      open group in terms of age, body mass index, previous surgery, FIGO stage,
      pathologic type, etc. (P > 0.05). The mean duration of surgery in the
      laparoscopic group was significantly longer [(303.8 +/- 67.5) min vs. (272.4 +/-
      57.5) min] (P < 0.01). But, the laparoscopic group had less blood loss [177.0 ml
      vs. 474.5 ml, P < 0.01] and blood transfusion rate [ 6.1% (2/33 cases) vs. 49.5%
      (50/101 cases), P < 0.001]. There was no significant difference regarding the
      proportion of patients who firstly passed the post-void residual urine volume
      (PVR) test (P > 0.05). The median time of catheterization between the two groups
      were also comparable (P > 0.05). However, the postoperative hospital stay was
      significantly shorter in the laparoscopic group [median postoperative hospital
      stay 9.2 days vs. 11.0 days, P < 0.001]. CONCLUSIONS: Laparoscopic NPSRH is
      feasible. It seems to be comparable with open NPSRH in terms of preserving pelvic
      nerve function, but is more favorable in terms of blood loss and postoperative
      recovery.

PMID- 24685091
TI  - [Clinical features of familial non-medullary thyroid cancer patients].
AB  - OBJECTIVE: To analyze the clinical features of familial non-medullary thyroid
      cancers, and to discuss their management. METHODS: Sixty thyroid cancer patients
      with familial non-medullary thyroid cancer (FNMTC) history during Sep. 2003 to
      Sep. 2012 were collected as study group, and another 60 sporadic thyroid cancer
      patients were randomly chosen as control. We compared the differences of their
      clinical features. RESULTS: All the patients were diagnosed as thyroid papillary
      carcinoma. The study group included 40 female and 20 male patients. There were 16
      cases in stage T1, 37 in stage T3, and 7 in stage T4. The patients were 21-66
      year old ( median age 42-years). The control group included 49 female and 11 male
      patients. The patients were 24- to 78-year old, and the median age was 45.5
      years. 43.3% of the patients in the study group and 18.3% of the patients in the
      control group had bilateral carcinomas (P = 0.003). There were multifocal lesions
      in 53.3% of the patients in the study group and 35.0% of the control group, local
      invasion in 73.3% of the patients in the study group and 55.0% of the control
      group, and coexisting benign thyroid diseases in 81.7% of the patients of the
      study group and 50.0% of the control group (P < 0.05 for all). There were
      cervical lymph node metastases in 60.0% of the patients in the study group and
      38.3% in the control group (P = 0.018). In the study group, 32 cases were of
      parent-offspring type and 28 cases of sibling type. Among the parent-offspring
      type patients, the median onset age of the first generation offsprings was 58
      years, and that of the second generation offsprings was 32 years (P < 0.001).
      CONCLUSIONS: Familial nonmedullary thyroid cancer, especially in parent-offspring
      type patients, is more aggressive than sporadic nonmedullary thyroid cancer, and
      often involves bilateral lobes, has multifocality, and combines with benign
      thyroid diseases. We recommend a total thyroidectomy for treatment, and to screen
      all the family members >20 years old, with ultrasonography for early diagnosis
      and treatment.

PMID- 24685092
TI  - [Clinicopathological characteristics of colorectal cancer complicated with type 2
      diabetes mellitus: analysis of clinicopathological data from 3, 202 colorectal
      cancer patients].
AB  - OBJECTIVE: the aim of this study was to determine the clinicopathological
      characteristics of colorectal cancer (CRC) patients complicated with type 2
      diabetes mellitus (T2DM ). METHODS: A total of 3, 202 patients with CRC confirmed
      pathologically in Tianjin Union Medicine Center from January 2005 to December
      2009 were included in this study. We analyzed the differences in
      clinicopathological features between T2DM patients and non-diabetic patients
      according to age of diagnosis, gender, tumor site, stage, gross type,
      histological type, and differentiation. RESULTS: From 2005 to 2009, the number of
      CRC patients increased yearly. The high incidence age of all CRC patients was 51
      to 80 years old. The male to female ratio was 1.18:1, showing that the number of
      female patients with CRC was increased significantly compared with males. The CRC
      distribution of T2DM patients and non-diabetic patients showed a predominance of
      rectal cancer (64.4%, 68.7%), followed by sigmoid colon cancer (12.5%, 13.0%),
      and moderately differentiated ulcer-type adenocarcinoma. Compared with non
      diabetic patients, T2DM patients were older (66.2 years versus 62.7 years, P <
      0.001) and had more multiple CRCs (3.5% versus 1.6%, P < 0.001). Moreover, the
      proportion of lymph node or organ metastasis in T2DM patients was higher than
      that in non-diabetic patients (52.6% versus 45.6%, P < 0.05). No significant
      differences were observed between both groups in terms of gender, gross type,
      histological type, and differentiation(P > 0.05 for all). CONCLUSIONS: CRC
      incidence shows an increasing trend with age. CRC patients with T2DM have an
      older age of onset, higher proportion of lymph node and distant organ metastasis
      than in non-diabetic patients.

PMID- 24685093
TI  - Autonomic regulation of cellular immune function.
AB  - The nervous system and the immune system (IS) are two integrative systems that
      work together to detect threats and provide host defense, and to maintain/restore
      homeostasis. Cross-talk between the nervous system and the IS is vital for health
      and well-being. One of the major neural pathways responsible for regulating host
      defense against injury and foreign antigens and pathogens is the sympathetic
      nervous system (SNS). Stimulation of adrenergic receptors (ARs) on immune cells
      regulates immune cell development, survival, proliferative capacity, circulation,
      trafficking for immune surveillance and recruitment, and directs the cell surface
      expression of molecules and cytokine production important for cell-to-cell
      interactions necessary for a coordinated immune response. Finally, AR stimulation
      of effector immune cells regulates the activational state of immune cells and
      modulates their functional capacity. This review focuses on our current
      understanding of the role of the SNS in regulating host defense and immune
      homeostasis. SNS regulation of IS functioning is a critical link to the
      development and exacerbation of chronic immune-mediated diseases. However, there
      are many mechanisms that need to be further unraveled in order to develop sound
      treatment strategies that act on neural-immune interaction to resolve or prevent
      chronic inflammatory diseases, and to improve health and quality of life. 

PMID- 24685094
TI  - Rapid protein profiling facilitates surveillance of invasive mosquito species.
AB  - BACKGROUND: Invasive aedine mosquito species have become a major issue in many
      parts of the world as most of them are recognised vectors or potentially involved
      in transmission of pathogens. Surveillance of these mosquitoes (e.g. Ae. aegypti,
      Yellow fever mosquito, Aedes albopictus, Asian tiger mosquito) is mainly done by
      collecting eggs using ovitraps and by identification of the larvae hatched in the
      laboratory. In order to replace this challenging and laborious procedure, we have
      evaluated matrix-assisted laser desorption/ionization time of flight mass
      spectrometry (MALDI-TOF MS) for easy and rapid species identification. METHODS:
      Individual protein profiles were generated using five eggs each of nine aedine
      species (Ae. aegypti, Ae. albopictus, Ae. atropalpus, Ae. cretinus, Ae.
      geniculatus, Ae. japonicus, Ae. koreicus, Ae. phoeniciae, Ae. triseriatus) from
      various geographical origins, and species-specific biomarker mass sets could be
      generated. A blinded validation using our reference data base for automated egg
      identification was performed. In addition, pools of 10 aedine eggs (132 two
      species and 18 three-species pools) in different ratios were evaluated. RESULTS:
      Specific biomarker mass sets comprising 18 marker masses could be generated for
      eggs of nine container-inhabiting aedine species, including all the major
      invasive and indigenous species of Europe and North America. Two additional
      masses shared by all investigated aedine species are used as internal
      calibrators. Identification of single eggs was highly accurate (100% specificity,
      98.75% sensitivity), and this method is also of value for the identification of
      species in pools of ten eggs. When mixing two or three species, all were
      identified in all pools in at least 2 or 1 of the 4 loaded replicates,
      respectively, if the "lesser abundant" species in the pool accounted for three or
      more eggs. CONCLUSIONS: MALDI-TOF MS, which is widely applied for routine
      identification of microorganisms in clinical microbiology laboratories, is also
      suited for robust, low-cost and high throughput identification of mosquito
      vectors in surveillance programmes. This tool can further be developed to include
      a wide spectrum of arthropods but also other Metazoa for which surveillance is
      required, and might become the method of choice for their centralised
      identification via online platforms.

PMID- 24685095
TI  - High risk for obesity in children with a subtype of developmental coordination
      disorder.
AB  - The purpose of this study was to compare the prevalence of overweight and obesity
      in typically developing (TD) children, children with developmental coordination
      disorder (DCD) and balance problems (DCD-BP), and children with DCD without
      balance problems (DCD-NBP). Two thousand and fifty-seven children (1095 boys, 962
      girls) ages 9-12 years were recruited from 18 elementary schools in Taiwan. The
      Movement Assessment Battery for Children was used to assess motor coordination
      ability. International cut-off points for body mass index were used to classify
      participants into the following groups: normal-weight, overweight or obese.
      Compared with TD children, children in the DCD-BP group were more than twice as
      likely to be obese (OR=2.28; 95% CI=1.41-3.68). DCD-BP children were also more
      likely to be obese compared to DCD-NBP children (OR=1.79; 95% CI=1.02-3.16). Boys
      in the DCD-BP group were more likely to be obese when compared to DCD-BP girls
      (OR=3.12; 95% CI=1.28-7.57). Similarly, DCD-NBP boys were more likely to be obese
      when compared to DCD-NBP girls (OR=2.67; 95% CI=1.21-5.89). Children with both
      DCD and BP were significantly more likely to be obese when compared to TD and DCD
      NBP children. From an intervention perspective, the inclusion of regular physical
      activity, including activities that encourage development of both balance and
      energy expenditure, may be required to prevent obesity in this population. 

PMID- 24685096
TI  - The link between impaired theory of mind and executive function in children with
      cerebral palsy.
AB  - The aim of the study was to explore the relationship between theory of mind (ToM)
      deficits and executive function (EF) impairments in children with cerebral palsy
      (CP), 42 CP with children and 42 typically developing (TD) children, acting as
      controls, were assessed on the tasks of ToM (false belief and faux pas) and EF
      (inhibition, updating and shifting). Results showed that CP children had deficits
      both in ToM and EF tasks. The correlation analyses showed that two EF components
      (inhibition and updating) were strongly related to false belief and faux pas in
      both two groups. We also found correlation between shifting and false belief and
      faux pas. However, this correlation was only found in TD children and not in
      children with CP. These findings suggest that children with CP lag behind TD
      children in both ToM and EF. Further, the results reveal, interestingly, that ToM
      deficits in CP children might be related to their inhibition and updating
      impairments, but not to shifting impairments.

PMID- 24685097
TI  - Psychometric properties of the DCDDaily-Q: a new parental questionnaire on
      children's performance in activities of daily living.
AB  - Difficulties in the performance of activities of daily living (ADL) are a key
      feature of developmental coordination disorder (DCD). The DCDDaily-Q was
      developed to address children's motor performance in a comprehensive range ADL.
      The aim of this study was to investigate the psychometric properties of this
      parental questionnaire. Parents of 218 five to eight year-old children (DCD
      group: N=25; reference group: N=193) completed the research version of the new
      DCDDaily-Q and the Movement Assessment Battery for Children-2 (MABC2) Checklist
      and Developmental Coordination Disorder Questionnaire (DCDQ). Children were
      assessed with the MABC2 and DCDDaily. Item reduction analyses were performed and
      reliability (internal consistency and factor structure) and concurrent,
      discriminant, and incremental validity of the DCDDaily-Q were investigated. The
      final version of the DCDDaily-Q comprises 23 items that cover three underlying
      factors and shows good internal consistency (Cronbach's alpha>.80). Moderate
      correlations were found between the DCDDaily-Q and the other instruments used
      (p<.001 for the reference group; p>.05 for the DCD group). Discriminant validity
      of the DCDDaily-Q was good for DCDDaily-Q total scores (p<.001) and all 23 item
      scores (p<.01), indicating poorer performance in the DCD group. Sensitivity (88%)
      and specificity (92%) were good. The DCDDaily-Q better predicted DCD than
      currently used questionnaires (R(2)=.88). In conclusion, the DCDDaily-Q is a
      valid and reliable questionnaire to address children's ADL performance.

PMID- 24685098
TI  - Maximal and submaximal mouth opening with mouth gags in cats: implications for
      maxillary artery blood flow.
AB  - The use of spring-loaded mouth gags in cats can be associated with the
      development of central neurological deficits, including blindness. In this
      species, the maxillary arteries are the main source of blood supply to the
      retinae and brain. Spring-loaded gags generate constant force after placement
      that could contribute to bulging of the soft tissues between the mandible and the
      tympanic bulla. Under these circumstances, the maxillary arteries can become
      compressed as they course between these osseous structures. Smaller gags that
      might apply less force to the mouth were investigated to determine if they
      preserved maxillary artery blood flow. Six healthy adult cats were anesthetized.
      Electroretinography (ERG) and magnetic resonance angiography (MRA) were performed
      without the use of a mouth gag and during submaximal (plastic mouth gags of 20,
      30 and 42 mm in length between canine teeth) and maximal mouth opening. Maximal
      mouth opening produced alterations in ERG waveforms consistent with circulatory
      compromise in 1/6 cats and reductions in signal intensity during MRA in 4/6 cats.
      Placement of a 42 mm plastic gag produced a reduction in MRA signal in 1/6 cats.
      No changes were observed with smaller gags. The force applied against the mouth
      was significantly higher with the spring-loaded gag than with any other gags. The
      use of a smaller mouth gags was associated with fewer alterations of indicators
      of maxillary artery blood flow. Nevertheless, a 42 mm plastic gag, equivalent to
      the size of a needle cap, resulted in an abnormal MRA in one cat.

PMID- 24685099
TI  - Macrolides and lincosamides in cattle and pigs: use and development of
      antimicrobial resistance.
AB  - Macrolides and lincosamides are important antibacterials for the treatment of
      many common infections in cattle and pigs. Products for in-feed medication with
      these compounds in combination with other antimicrobials are commonly used in
      Europe. Most recently approved injectable macrolides have very long elimination
      half-lives in both pigs and cattle, which allows once-only dosing regimens. Both
      in-feed medication and use of long-acting injections result in low concentrations
      of the active substance for prolonged periods, which causes concerns related to
      development of antimicrobial resistance. Acquired resistance to macrolides and
      lincosamides among food animal pathogens, including some zoonotic bacteria, has
      now emerged. A comparison of studies on the prevalence of resistance is
      difficult, since for many micro-organisms no agreed standards for susceptibility
      testing are available. With animal pathogens, the most dramatic increase in
      resistance has been seen in the genus Brachyspira. Resistance towards macrolides
      and lincosamides has also been detected in staphylococci isolated from pigs and
      streptococci from cattle. This article reviews the use of macrolides and
      lincosamides in cattle and pigs, as well as the development of resistance in
      target and some zoonotic pathogens. The focus of the review is on European
      conditions. 

PMID- 24685100
TI  - Test and cull of high risk Coxiella burnetii infected pregnant dairy goats is not
      feasible due to poor test performance.
AB  - A major human Q fever epidemic occurred in The Netherlands during 2007-2009. In
      response, all pregnant goats from infected herds were culled before the 2010
      kidding season without individual testing. The aim of this study was to assess
      whether high risk animals from recently infected naive herds can be identified by
      diagnostic testing. Samples of uterine fluid, milk and vaginal mucus from 203
      euthanized pregnant goats were tested by PCR or ELISA. The results suggest that
      testing followed by culling of only the high risk animals is not a feasible
      method for protecting public health, mainly due to the low specificity of the
      tests and variability between herds. The risk of massive bacterial shedding
      during abortion or parturition can only be prevented by removal of all pregnant
      animals from naive recently infected herds. 

PMID- 24685101
TI  - Empathic veterinarians score cattle pain higher.
AB  - The treatment of cattle pain often relies upon veterinarians. The aim of this
      study was to qualify the influence of veterinarians skills, attitudes, and
      empathy on cattle pain assesment and consequently disbudding pain management. A
      web-based questionnaire was sent to Finnish veterinary students in either the
      preclinical or clinical stage, and also to production-animal practice oriented
      veterinarians. The questionnaire recorded demographics, statements of opinions,
      pain scoring of cattle conditions and procedures. Empathy towards humans
      (Interpersonal Reactivity Index, IRI) and reworded IRI to measure empathy towards
      animals were also covered. The overall response rate was approximately 40%. The
      association between pain and empathy scores were analyzed by Pearsons
      correlation, and the factors affecting pain scores and empathy towards animals
      analyzed using linear models. The need for pain medication of calves during
      disbudding was well recognized and the intention to treat such pain was very
      common. Higher mean scores for cattle pain were associated with greater empathy
      towards humans. On average, respondents' empathy towards animals was greater than
      towards humans, and was associated with respondents' empathy towards humans,
      family size and attachment to family pet.

PMID- 24685102
TI  - The effect of injectable trace minerals (selenium, copper, zinc, and manganese)
      on peripheral blood leukocyte activity and serum superoxide dismutase activity of
      lactating Holstein cows.
AB  - The objective of this study was to evaluate the effect of subcutaneous
      supplementation of 300 mg of zinc, 50 mg of manganese, 25 mg of selenium, and 75
      mg of copper on peripheral blood leukocyte activity and serum beta
      hydroxybutyrate (BHBA) concentrations at 10 +/- 2 days in milk (DIM), and on
      serum superoxide dismutase (SOD) activity during the transition period and
      subsequent lactation of multiparous Holstein cows. A total of 250 multiparous
      cows were randomly allocated into one of two treatments groups, namely, trace
      mineral supplemented (TMS) or control. Cows in the TMS group were injected at 230
      and 260 days of gestation, and 35 days postpartum. Serum SOD activity was
      measured at enrollment, and 10, 60 and 100 DIM. Serum BHBA concentration and
      leukocyte function were assessed at 10 DIM. Overall serum SOD activity for TMS
      and control was 16.01 and 12.71 U/mL, respectively. The interaction between
      treatment and time of serum collection was significant. Additionally, overall
      serum SOD activity was 12.85 and 14.78 U/mL for cows diagnosed with mastitis and
      unaffected cows, respectively. Treatment did not affect leukocyte function. For
      parity >2, TMS cows had lower serum BHBA concentrations than control cows; BHBA
      concentrations were 0.41 and 0.27 mmol/L for control and TMS cows, respectively.
      In conclusion, cows diagnosed with mastitis had decreased serum SOD activity, and
      trace mineral supplementation increased serum SOD activity although leukocyte
      function was not affected by supplementation.

PMID- 24685103
TI  - Production impact of a targeted selective treatment system based on liveweight
      gain in a commercial flock.
AB  - The sustainability of sheep production is hindered by anthelmintic resistance.
      Options to slow down or prevent resistance have been widely studied but their
      application in the field is still limited. In this study, the practical
      application and effect of a targeted selective treatment (TST) approach for the
      treatment of parasitic gastroenteritis was investigated in lambs (n = 385) over a
      2 year period. At 14-day intervals during the grazing season, liveweight, breech
      soiling and anthelmintic treatments were individually recorded. Selection of
      lambs for anthelmintic treatment in the TST group was based on pre-calculated
      individual growth rates, with a matched cohort routinely treated (RT) with
      anthelmintic drug every 6 weeks. The adoption of a TST approach had no negative
      effect on the liveweight gains of the lambs, time to finishing or breech soiling
      measures compared to RT lambs; however a 50% decrease in anthelmintic treatment
      was observed in the TST group. The time to implement this system averaged 2 min
      per lamb. It is concluded that the TST could be suitable for commercial sheep
      farms, in association with automated weighing systems, potentially reducing
      selection for anthelmintic resistance, while having no negative effect on
      production.

PMID- 24685104
TI  - Bluetongue, Schmallenberg - what is next? Culicoides-borne viral diseases in the
      21st Century.
AB  - In the past decade, two pathogens transmitted by Culicoides biting midges
      (Diptera: Ceratopogonidae), bluetongue virus and Schmallenberg virus, have caused
      serious economic losses to the European livestock industry, most notably
      affecting sheep and cattle. These outbreaks of arboviral disease have highlighted
      large knowledge gaps on the biology and ecology of indigenous Culicoides species.
      With these research gaps in mind, and as a means of assessing what potential
      disease outbreaks to expect in the future, an international workshop was held in
      May 2013 at Wageningen University, The Netherlands. It brought together research
      groups from Belgium, France, Germany, Spain, Switzerland, United Kingdom and The
      Netherlands, with diverse backgrounds in vector ecology, epidemiology,
      entomology, virology, animal health, modelling, and genetics. Here, we report on
      the key findings of this workshop. 

PMID- 24685105
TI  - Moral discourses and pharmaceuticalised governance in households.
AB  - This article extends our understanding of the everyday practices of
      pharmaceuticalisation through an examination of moral concerns over medication
      practices in the household. Moral concerns of responsibility and discipline in
      relation to pharmaceutical consumption have been identified, such as passive or
      active medication practices, and adherence to orthodox or unorthodox accounts.
      This paper further delineates dimensions of the moral evaluations of
      pharmaceuticals. In 2010 and 2011 data were collected from 55 households across
      New Zealand and data collection techniques, such as photo- and diary-elicitation
      interviews, allowed the participants to develop and articulate reflective stories
      of the moral meaning of pharmaceuticals. Four repertoires were identified: a
      disordering society repertoire where pharmaceuticals evoke a society in an
      unnatural state; a disordering self repertoire where pharmaceuticals signify a
      moral failing of the individual; a disordering substances repertoire where
      pharmaceuticals signify a threat to one's physical or mental equilibrium; a re
      ordering substances repertoire where pharmaceuticals signify the restoration of
      function. The research demonstrated that the dichotomies of orthodox/unorthodox
      and compliance/resistance do not adequately capture how medications are used and
      understood in everyday practice. Attitudes change according to why
      pharmaceuticals are taken and who is taking them, their impacts on social
      relationships, and different views on the social or natural production of
      disease, the power of the pharmaceutical industry, and the role of health
      experts. Pharmaceuticals are tied to our identity, what we want to show of
      ourselves, and what sort of world we see ourselves living in. The ordering and
      disordering understandings of pharmaceuticals intersect with forms of
      pharmaceuticalised governance, where conduct is governed through pharmaceutical
      routines, and where self-responsibility entails following the prescription of
      other agents. Pharmaceuticals symbolise forms of governance with different sets
      of roles and responsibilities. 

PMID- 24685108
TI  - Interaction of genes and nutritional factors in the etiology of autism and
      attention deficit/hyperactivity disorders: a case control study.
AB  - OBJECTIVE: To compare risk factors of attention deficit/hyperactivity disorder
      (ADHD) and autism spectrum disorder (ASD) to age/sex-matched controls with
      particular attention to family history, parental age and nutrition. METHOD: 31
      ASD and 81 ADHD patients were compared to 612 age/sex-matched controls by
      reviewing charts for parental age, sibling order, gestational age, and early
      feeding, and by parental interview for early feeding and family history of
      psychopathology on affected patients and 139 of those controls. FINDINGS:
      Parental age affected ASD and ADHD females but not males. First-born males were
      at increased risk for both disorders even though their siblings had older parents
      and their parents were not more likely to stop having children. Breastfeeding in
      the absence of parental psychopathology reduced ADHD risk, but breastfeeding of
      first-born males by older mothers with psychopathology was a risk for ASD.
      Breastfeeding was only a risk for ADHD if the mother had psychopathology. Parent
      emigration from a place of high fish consumption was a significant ASD risk
      factor. RESULTING HYPOTHESES: ADHD and ASD share risk factors due to shared
      genetic and nutritional interactions, likely revolving around deficiencies of
      omega-3 fatty acids (n3FAs) during brain development. Fatty acid metabolism genes
      are important in that process. The 4:1 male to female ratio for both disorders
      results from hormonally driven fat metabolism differences. Risk factors for both
      disorders including maternal smoking, prematurity, and gestational diabetes may
      also be attributed to their effect on n3FA supplies. Breastfeeding can be a risk
      factor when the mother's genes and/or age affect her milk quality. Parental age
      and gene defects may affect female more than male offspring. Childbirth with
      adequate spacing and breastfeeding can override maternal age and protect
      subsequent offspring. Genetic variations in fat metabolism can be influenced by
      cultural/geographic diet, causing deficiencies in offspring with migration
      influenced diet changes. Interaction of n3FA deficient diets, delayed child
      bearing, and breastfeeding by mothers with psychopathology may be important
      factors in the rising incidence of ASD and ADHD in recent decades. Partial
      prevention through diet and supplements may be possible.

PMID- 24685106
TI  - Neural stem cells: are they the hope of a better life for patients with fetal
      onset hydrocephalus?
AB  - I was honored to be awarded the Casey Holter Essay Prize in 2013 by the Society
      for Research into Hydrocephalus and Spina Bifida. The purpose of the prize is to
      encourage original thinking in a way to improve the care of individuals with
      spina bifida and hydrocephalus. Having kept this purpose in mind, I have chosen
      the title: Neural stem cells, are they the hope of a better life for patients
      with fetal-onset hydrocephalus? The aim is to review and discuss some of the most
      recent and relevant findings regarding mechanisms leading to both hydrocephalus
      and abnormal neuro/gliogenesis. By looking at these outcome studies, it is hoped
      that we will recognize the potential use of neural stem cells in the treatment of
      hydrocephalus, and so prevent the disease or diminish/repair the associated brain
      damage. 

PMID- 24685107
TI  - Leukemic phase of ALK(+) anaplastic large-cell lymphoma, small-cell variant:
      clinicopathologic pitfalls of a rare entity.

PMID- 24685110
TI  - Are caesarean sections, induced labor and oxytocin regulation linked to Autism
      Spectrum Disorders?
AB  - The etiology of Autism Spectrum Disorders (ASDs) continues to be elusive. While
      ASDs have been shown to be heritable, several environmental co-factors, such as,
      e.g. pre- or perinatal adverse events, could play a role in the pathogenesis of
      the disorder as well. Prevalence of ASDs appears to have increased in the last
      three decades, but the causes of this surge are not fully understood. As
      perinatal adverse events have increased as well, they have been regarded as
      logical contributors to the risen prevalence of ASDs. Over the last three decades
      there has been also a considerable increase in the rates of induced labor and
      caesarean sections (CS). However, even if a causal association between CS and
      ASDs increase has been suggested, it has not yet been proven. Nevertheless, we
      hypothesize here that such an association is actual and that it might help to
      explain a part of the increase in ASD diagnoses. Our assumption is based on the
      wider epidemiological picture of ASDs and CS, as well as on the possible
      biological plausibility of this correlation, by postulating potential epigenetic
      and neurobiological mechanisms underpinning this relationship. Today, several
      observations point toward the existence of epigenetic dysregulation in ASDs and
      this raises the issue of the role of environmental factors in bringing about
      epigenetic modifications. Epigenetic dysregulations in some brain neuropeptide
      systems could play a role in the behavioral dysfunctions of ASDs. Particularly,
      some evidence suggests a dysregulation of the oxytocinergic system in autistic
      brains. Perinatal alterations of oxytocin (OT) can also have life-long lasting
      effects on the development of social behaviors. Within the perinatal period,
      various processes, like pitocin infusion or CS, can alter the OT balance in the
      newborn; OT dysregulation could then interact with genetic factors, leading
      ultimately to the development of ASDs. Large long-term prospective studies are
      needed to identify causal pathways for ASDs and examine whether and how (epi
      )genetic susceptibility interacts with obstetric risk factors in the development
      of ASDs. A better understanding of such a potential interplay could become
      paradigmatic for a wide range of genetic-environmental interactions in ASDs. 

PMID- 24685109
TI  - Next target of tranilast: inhibition of corneal neovascularization.
AB  - Corneal neovascularization (CN) which is associated with angiogenesis and
      inflammation is seen in different pathological conditions. Among all these
      situations inflammation and angiogenesis factors such as vascular endothelial
      growth factor (VEGF), matrix metalo proteinases (MMPs), tumor necrosis factor
      alpha (TNF-alpha) and other related factors are involved in CN regardless of the
      etiology. Thus inhibition of these agents that lead to suppression of
      angiogenesis and inflammation is one the most important strategies to treat CN.
      Tranilast (TR) is an anti-allergic medicine which has been used in Japan and
      South Korea in clinic. TR is able to inhibit VEGF, MMP-2 and MMP-9, TNF-alpha and
      some other angiogenic and inflammatory factors. According to the anti-angiogenic
      and anti-inflammatory activity of TR, we hypothesize on the probable efficacy of
      TR in treating CN. Also topical application of TR in human eye is reported to be
      safe, so it would be easier to have additional research on therapeutic potential
      of TR in clinic. 

PMID- 24685111
TI  - Are emotional labour strategies by nurses associated with psychological costs? A
      cross-sectional survey.
AB  - BACKGROUND: Emotional labour is an integral part of the role of nurses with
      surface and deep acting as the core emotional labour strategies. Surface acting
      involves the regulation of emotional expression with the aim of bringing it in
      line with organizational display rules, whereas deep acting aims at modifying the
      situation or perception of situations in order to change felt emotions,
      accordingly. OBJECTIVES: Since surface acting is thought to consume more
      cognitive control resources than deep acting, the study examines whether nurses'
      cognitive control deficits as a stable personal vulnerability factor exert
      stronger adverse interactive influences with surface acting on job strain than
      with deep acting. DESIGN: A cross-sectional questionnaire survey was conducted in
      combination with absence data referring to a time period of 12 months after
      administration of the questionnaires. SETTING: A hospital and three nursing homes
      for the elderly located in a federal state in Germany. PARTICIPANTS:
      Questionnaires were distributed to the whole nursing staff of which 195 nurses
      filled in the questionnaire and permitted collecting their absence data (73%
      participation rate). METHODS: In addition to descriptive statistics and bivariate
      correlations, confirmatory factor analyses and hierarchical moderated regression
      analyses were performed. RESULTS: Findings revealed significant positive
      relations of surface acting and cognitive control deficits with indicators of job
      strain, whereas deep acting was unrelated to strain. In addition, surface acting
      was found to interact stronger with cognitive control deficits in its relation to
      strain than deep acting. Compared to nurses with low levels of cognitive control
      deficits, the adverse influences of surface acting on burnout, depressive
      symptoms, and sum of days absent were much stronger when high levels of cognitive
      control deficits were reported. CONCLUSIONS: Consequently, interventions are
      needed to inform nurses on the detrimental influences of surface acting and train
      them in the daily use of deep acting as the healthier emotional regulation
      strategy. In addition, interventions targeted at the enhancement of the
      individual capacity for self-control would be beneficial to nurses' health.

PMID- 24685112
TI  - Anthranilic acid derivatives as novel ligands for farnesoid X receptor (FXR).
AB  - Nuclear farnesoid X receptor (FXR) has important physiological roles in various
      metabolic pathways including bile acid, cholesterol and glucose homeostasis. The
      clinical use of known synthetic non-steroidal FXR ligands is restricted due to
      toxicity or poor bioavailability. Here we report the development, synthesis, in
      vitro activity and structure-activity relationship (SAR) of anthranilic acid
      derivatives as novel FXR ligands. Starting from a virtual screening hit we
      optimized the scaffold to a series of potent partial FXR agonists with appealing
      drug-like properties. The most potent derivative exhibited an EC50 value of 1.5+/
      0.2 MUM and 37+/-2% maximum relative FXR activation. We investigated its SAR
      regarding polar interactions with the receptor by generating derivatives and
      computational docking.

PMID- 24685113
TI  - Development of 3,5-dinitrobenzoate-based 5-lipoxygenase inhibitors.
AB  - Human 5-lipoxygenase (5-LOX) is a well-validated target for anti-inflammatory
      therapy. Development of novel 5-LOX inhibitors with higher activities is highly
      demanded. In previous study, we have built a model for the active conformation of
      human 5-LOX, and identified naphthalen-1-yl 3,5-dinitrobenzoate (JMC-4) as a 5
      LOX inhibitor by virtual screening. In the present work, 3,5-dinitrobenzoate
      based 5-lipoxygenase inhibitors were developed. Twenty aryl 3,5-dinitrobenzoates,
      N-aryl 3,5-dinitrobenzamides and analogues were designed and synthesized. Several
      of them were found with significantly increased activities according to cell-free
      assay and human whole blood assay. The structure-activity relationship study may
      provide useful insights for designing effective 5-LOX inhibitors. 

PMID- 24685114
TI  - Molecular hydrogen suppresses reactive astrogliosis related to oxidative injury
      during spinal cord injury in rats.
AB  - AIMS: Spinal cord injury (SCI) can induce excessive astrocyte activation.
      Hydrogen has been deemed as a novel antioxidant. We investigated whether
      molecular hydrogen could act as an antiastrogliosis agent during SCI and
      oxidative injury in experimental rats and cultured astrocytes. METHODS: Hydrogen
      rich saline (HS, 8 mL/kg, i.p.) was injected every 12 h after SCI in rats. The
      expression of STAT3, p-STAT3, and glial fibrillary acidic protein (GFAP); the
      release of IL-1beta, IL-6, and TNF-alpha; and astrogliosis, along with the BBB
      score, were evaluated. Culturing astrocytes with hydrogen-rich medium, the
      intracellular reactive oxygen species (ROS), astrogliosis, and the release of
      proinflammatory cytokines were assessed after H2O2-induced injury. RESULTS: In
      the HS group, the expression of STAT3, p-STAT3, and GFAP and the proinflammatory
      cytokines were decreased in local spinal cord on postoperation day (POD) 3; on
      PODs 7 and 14, reactive astrogliosis was suppressed, and the locomotor function
      was also improved. Furthermore, hydrogen-rich medium attenuated the intracellular
      production of ROS (especially HO*), astrogliosis, and the secretion of
      proinflammatory cytokines in astrocytes 12 h after H2O2-induced injury.
      CONCLUSIONS: Molecular hydrogen could suppress reactive astrogliosis after
      contusive SCI and reduce the release of proinflammatory cytokines produced by
      active astrocytes related to oxidative injury. Thus, molecular hydrogen is
      potential to be a neuroprotective agent.

PMID- 24685115
TI  - Optimum deposition conditions of ultrasmooth silver nanolayers.
AB  - Reduction of surface plasmon-polariton losses due to their scattering on metal
      surface roughness still remains a challenge in the fabrication of plasmonic
      devices for nanooptics. To achieve smooth silver films, we study the dependence
      of surface roughness on the evaporation temperature in a physical vapor
      deposition process. At the deposition temperature range 90 to 500 K, the mismatch
      of thermal expansion coefficients of Ag, Ge wetting layer, and sapphire substrate
      does not deteriorate the metal surface. To avoid ice crystal formation on
      substrates, the working temperature of the whole physical vapor deposition
      process should exceed that of the sublimation at the evaporation pressure range.
      At optimum room temperature, the root-mean-square (RMS) surface roughness was
      successfully reduced to 0.2 nm for a 10-nm Ag layer on sapphire substrate with a
      1-nm germanium wetting interlayer. Silver layers of 10- and 30-nm thickness were
      examined using an atomic force microscope (AFM), X-ray reflectometry (XRR), and
      two-dimensional X-ray diffraction (XRD2). PACS: 63.22.Np Layered systems; 68.
      Surfaces and interfaces; thin films and nanosystems (structure and nonelectronic
      properties); 81.07.-b Nanoscale materials and structures: fabrication and
      characterization.

PMID- 24685116
TI  - Clinical characteristics of people experiencing biochemical hypoglycaemia during
      an oral glucose tolerance test: cross-sectional analyses from a UK multi-ethnic
      population.
AB  - AIMS: People who experience biochemical hypoglycaemia during an oral glucose
      tolerance test (OGTT) may be insulin resistant, but this has not been
      investigated robustly, therefore we examined this in a population-based multi
      ethnic UK study. METHODS: Cross-sectional data from 6478 diabetes-free
      participants (849 with fasting insulin data available) who had an OGTT in the
      ADDITION-Leicester screening study (2005-2009) were analysed. People with
      biochemical hypoglycaemia (2-h glucose <3.3mmol/l) were compared with people with
      normal glucose tolerance (NGT) or impaired glucose regulation (IGR) using
      regression methods. RESULTS: 359 participants (5.5%) had biochemical
      hypoglycaemia, 1079 (16.7%) IGR and 5040 (77.8%) NGT. Biochemical hypoglycaemia
      was associated with younger age (P<0.01), white European ethnicity (P<0.001),
      higher HDL cholesterol (P<0.01), higher insulin sensitivity (P<0.05), and lower
      body mass index (P<0.001), blood pressure (P<0.01), fasting glucose (P<0.001),
      HbA1C (P<0.01), and triglycerides (P<0.01) compared with NGT and IGR separately
      in both unadjusted and adjusted (age, sex, ethnicity, body mass index, smoking
      status) models. CONCLUSIONS: Biochemical hypoglycaemia during an OGTT in the
      absence of diabetes or IGR was not associated with insulin resistance, but
      instead appeared to be associated with more favourable glycaemic risk profiles
      than IGR and NGT. Thus, clinicians may not need to intervene due to biochemical
      hypoglycaemia on a 2-h OGTT.

PMID- 24685117
TI  - Can an alert in primary care electronic medical records increase participation in
      a population-based screening programme for colorectal cancer? COLO-ALERT, a
      randomised clinical trial.
AB  - BACKGROUND: Colorectal cancer is an important public health problem in Spain.
      Over the last decade, several regions have carried out screening programmes, but
      population participation rates remain below recommended European goals. Reminders
      on electronic medical records have been identified as a low-cost and high-reach
      strategy to increase participation. Further knowledge is needed about their
      effect in a population-based screening programme. The main aim of this study is
      to evaluate the effectiveness of an electronic reminder to promote the
      participation in a population-based colorectal cancer screening programme.
      Secondary aims are to learn population's reasons for refusing to take part in the
      screening programme and to find out the health professionals' opinion about the
      official programme implementation and on the new computerised tool.
      METHODS/DESIGN: This is a parallel randomised trial with a cross-sectional second
      stage. PARTICIPANTS: all the invited subjects to participate in the public
      colorectal cancer screening programme that includes men and women aged between 50
      69, allocated to the eleven primary care centres of the study and all their
      health professionals. The randomisation unit will be the primary care physician.
      The intervention will consist of activating an electronic reminder, in the
      patient's electronic medical record, in order to promote colorectal cancer
      screening, during a synchronous medical appointment, throughout the year that the
      intervention takes place. A comparison of the screening rates will then take
      place, using the faecal occult blood test of the patients from the control and
      the intervention groups. We will also take a questionnaire to know the opinions
      of the health professionals. The main outcome is the screening status at the end
      of the study. Data will be analysed with an intention-to-treat approach.
      DISCUSSION: We expect that the introduction of specific reminders in electronic
      medical records, as a tool to facilitate and encourage direct referral by
      physicians and nurse practitioners to perform colorectal cancer screening will
      mean an increase in participation of the target population. The introduction of
      this new software tool will have good acceptance and increase compliance with
      recommendations from health professionals. TRIAL REGISTRATION: Clinical
      Trials.gov identifier NCT01877018.

PMID- 24685120
TI  - Changing practice to support self-management and recovery in mental illness:
      application of an implementation model.
AB  - Health services introducing practice changes need effective implementation
      methods. Within the setting of a community mental health service offering
      recovery-oriented psychosocial support for people with mental illness, we aimed
      to: (i) identify a well-founded implementation model; and (ii) assess its
      practical usefulness in introducing a new programme for recovery-oriented self
      management support. We reviewed the literature to identify implementation models
      applicable to community mental health organisations, and that also had
      corresponding measurement tools. We used one of these models to inform
      organisational change strategies. The literature review showed few models with
      corresponding tools. The Promoting Action on Research Implementation in Health
      Services (PARIHS) model and the related Organisational Readiness to Change
      Assessment (ORCA) tool were used. The PARIHS proposes prerequisites for health
      service change and the ORCA measures the extent to which these prerequisites are
      present. Application of the ORCA at two time points during implementation of the
      new programme showed strategy-related gains for some prerequisites but not for
      others, reflecting observed implementation progress. Additional strategies to
      address target prerequisites could be drawn from the PARIHS model. The PARIHS
      model and ORCA tool have potential in designing and monitoring practice change
      strategies in community mental health organisations. Further practical use and
      testing of implementation models appears justified in overcoming barriers to
      change.

PMID- 24685118
TI  - Models of care for orphaned and separated children and upholding children's
      rights: cross-sectional evidence from western Kenya.
AB  - BACKGROUND: Sub-Saharan Africa is home to approximately 55 million orphaned
      children. The growing orphan crisis has overwhelmed many communities and has
      weakened the ability of extended families to meet traditional care-taking
      expectations. Other models of care and support have emerged in sub-Saharan Africa
      to address the growing orphan crisis, yet there is a lack of information on these
      models available in the literature. We applied a human rights framework using the
      United Nations Convention on the Rights of the Child to understand what extent
      children's basic human rights were being upheld in institutional vs. community-
      or family-based care settings in Uasin Gishu County, Kenya. METHODS: The Orphaned
      and Separated Children's Assessments Related to their Health and Well-Being
      Project is a 5-year cohort of orphaned children and adolescents aged <=18 year.
      This descriptive analysis was restricted to baseline data. Chi-Square test was
      used to test for associations between categorical /dichotomous variables.
      Fisher's exact test was also used if some cells had expected value of less than
      5. RESULTS: Included in this analysis are data from 300 households, 19 Charitable
      Children's Institutions (CCIs) and 7 community-based organizations. In total,
      2871 children were enrolled and had baseline assessments done: 1390 in CCI's and
      1481 living in households in the community. We identified and described four
      broad models of care for orphaned and separated children, including:
      institutional care (sub-classified as 'Pure CCI' for those only providing
      residential care, 'CCI-Plus' for those providing both residential care and
      community-based supports to orphaned children , and 'CCI-Shelter' which are
      rescue, detention, or other short-term residential support), family-based care,
      community-based care and self-care. Children in institutional care (95%) were
      significantly (p < 0.0001) more likely to have their basic material needs met in
      comparison to those in family-based care (17%) and institutions were better able
      to provide an adequate standard of living. CONCLUSIONS: Each model of care we
      identified has strengths and weaknesses. The orphan crisis in sub-Saharan Africa
      requires a diversity of care environments in order to meet the needs of children
      and uphold their rights. Family-based care plays an essential role; however,
      households require increased support to adequately care for children.

PMID- 24685119
TI  - Review of brief cognitive tests for patients with suspected dementia.
AB  - BACKGROUND: As the population ages, it is increasingly important to use effective
      short cognitive tests for suspected dementia. We aimed to review systematically
      brief cognitive tests for suspected dementia and report on their validation in
      different settings, to help clinicians choose rapid and appropriate tests.
      METHODS: Electronic search for face-to-face sensitive and specific cognitive
      tests for people with suspected dementia, taking <= 20 minutes, providing
      quantitative psychometric data. RESULTS: 22 tests fitted criteria. Mini-Mental
      State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good
      psychometric properties in primary care. In the secondary care settings, MMSE has
      considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT),
      Brief Alzheimer's Screen, HVLT, and 7 Minute Screen have good properties for
      detecting dementia but need further validation. Addenbrooke's Cognitive
      Examination (ACE) and Montreal Cognitive Assessment are effective to detect
      dementia with Parkinson's disease and Addenbrooke's Cognitive Examination-Revised
      (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland
      Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests
      such as Test for Early Detection of Dementia, Test Your Memory, Cognitive
      Assessment Screening Test (CAST) and the recently developed ACE-III show promise
      but need validation in different settings, populations, and dementia subtypes.
      Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for
      dementia screening in acute hospital settings. CONCLUSIONS: Practitioners should
      use tests as appropriate to the setting and individual patient. More validation
      of available tests is needed rather than development of new ones.

PMID- 24685121
TI  - Dengue transmission model by means of viremic adult immuno-competent mouse.
AB  - BACKGROUND: Dengue virus infection manifests in three distinct forms in humans:
      dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Infection with
      the virus is a fatal disease; no vaccine is available and prevention depends on
      interruption of the chain of transmission. The study of dengue viral transmission
      by mosquitoes is hindered due to the lack of an affordable animal model. In
      general, immuno-competent mice are used as a simple and inexpensive animal model,
      but mice are not susceptible to dengue virus infection and therefore viremia will
      not occur following the inoculation of the virus in such mice. Here, we report a
      method for creating artificial viremia in immuno-competent mice, and further
      demonstrate the use of viremic mice to simultaneously infect a large number of
      Aedes aegypti. METHODS: We infected K562 cells with DENV-2 in the presence of an
      antibody against DENV-4. We then incubated the cells for 2 d before injecting the
      infected cells into C3H mice. After 5 h incubation, we allowed 100-150 female
      Aedes aegypti to feed on blood from the mice directly. We collected blood samples
      from the mice and from randomly selected Ae. aegypti at 2, 6, 12, and 24 h post
      blood meal and screened the samples for DENV-2 genome as well as for virus
      concentration. RESULTS: Our procedure provided high virus concentrations in the
      mice for at least 7 h after viral inoculation. We found that 13 out of 14
      randomly picked mosquitoes were infected with DENV-2. High concentrations of
      virus were detected in the mosquitoes until at least 12 h post-infection.
      CONCLUSIONS: Using the viremic immuno-competent mouse, we show that mass
      infection of Ae. aegypti is achievable. Compared to other infection techniques
      using direct inoculation, membrane-feeding, or immuno-deficient/humanized mice,
      we are confident that this method will provide a simpler and more efficient
      infection technique.

PMID- 24685122
TI  - A recent case of periorbital necrotizing fasciitis--presentation to definitive
      reconstruction within an in-theater combat hospital setting.
AB  - First described in 1924, necrotizing fasciitis (NF) is a rapidly progressing,
      severe suppurative infection of the superficial fascia, often associated with
      vascular thrombosis and necrosis of the overlying skin. Despite advances in
      medical therapy, the mortality remains high, with rates exceeding 25 to 50% in
      some studies. Early diagnosis and treatment is paramount in the management of
      this serious infection and should include wide surgical debridement and drainage
      of all necrotic tissues, coupled with aggressive parenteral antibiotics. This
      infectious process has been commonly associated with traumatic events in patients
      with compromised immune systems, diabetes, chronic steroid use, and alcoholism.
      The common microbacterial organisms associated with necrotizing fasciitis include
      Streptococcus pyogenes and Staphylococcus aureus and less commonly, facultative
      and anaerobic microorganisms. Most cases typically present in the extremities,
      trunk, and/or groin regions. Although this virulent soft tissue infection can
      occur within the face and neck areas, cases of isolated periorbital NF have been
      relatively uncommon. However, head and neck cases of NF have had high associated
      morbidity and mortality rates. In recent publications, the reported mortality
      rate for isolated periorbital NF was not insignificant, ranging from 8.5 to
      12.5%. The prognosis, morbidity, and mortality rates will be greatly increased in
      those patients who present late in the infectious phase, have a delay in
      diagnosis and/or treatment, or who demonstrate extension of this virulent
      infection into the face, cervical, or sternal/mediastinal regions. An aggressive
      multimodal approach is required in treating periorbital necrotizing infection,
      with the main tenant remaining wide and adequate surgical debridement of affected
      tissues. This difficult clinical situation can create a subsequent challenge with
      respect to achieving good functional and cosmetic outcomes in those patients with
      periorbital NF. Delayed reconstruction of the eyelids with skin grafts and/or
      facial flaps is often required to avoid late complications such as cicatricial
      lid retraction, lid malposition, exposure keratopathy, and potential loss of
      vision. We describe a patient who presented to a military combat hospital with a
      virulent periorbital soft tissue infection. We have outlined his treatment course
      from the initial presentation through definitive reconstruction.

PMID- 24685123
TI  - First bite syndrome after deep lobe parotidectomy: case report.
AB  - First bite syndrome (FBS) has recently been recognized in published medical
      studies; however, only 2 cases have been reported in dental studies. The syndrome
      was defined by Netterville and Civantos and Netterville et al as originating from
      a postoperative complication after parapharyngeal space (PPS) surgery. The most
      frequent reason for PPS surgery is the presence of a deep lobe parotid gland (PG)
      neoplasm, with cervical schwannoma the second most common lesion mandating
      surgery in this space. Surgical therapeutic procedures in the PPS for these
      tumors can inadvertently ablate the sympathetic nerve supply to the PG.
      Subsequently, with the first introduction of food into the mouth, severe intense
      and debilitating pain will develop and radiate through the upper neck, PG, and
      auricular regions on the ipsilateral surgical side. The intense pain will last
      approximately 5 seconds.With continued mastication, the pain will subside, but
      not totally abate. After the meal, the pain will gradually disappear, only to
      return with the next masticatory period. The pain is initiated by salivation,
      whether by food or the thought of food and will be accentuated by acidic
      sialogogic foods. Usually, with the passage of time, some gradual improvement in
      the intensity and frequency of the pain episodes can be anticipated. 

PMID- 24685124
TI  - Effect of enzyme replacement therapy on isokinetic strength for all major muscle
      groups in four patients with Pompe disease-a long-term follow-up.
AB  - Pompe disease is a rare, inherited metabolic myopathy characterized by
      progressive weakness of the proximal limb and respiratory muscles. We report the
      findings from four patients with late-onset Pompe disease treated with alpha
      glucosidase (Myozyme) for 2 (n=2) and 6 (n=2) years, and monitored with
      isokinetic dynamometry, 6-minute walking test (6MWT), and vital capacity.
      Patients were evaluated after 6, 12, 24, 36, 48, 60, and 72months. In two
      patients, muscle size estimated by MRI and DXA scanning was also performed prior
      to and following 6months of treatment. After 2years of alpha-glucosidase
      treatment, maximal isokinetic muscle strength increased by 11% (0%-50%) [median
      (range)] and 6MWT improved by 18% (2%-40%). In the two patients treated for
      6years, the increase in muscle strength stabilized at 40% and 6MWT stabilized at
      32%. The improvements primarily occurred during the first 6months of treatment.
      Interestingly, the weakest muscle groups seemed to benefit more than those less
      affected, and greater improvements occurred for flexor muscles compared to
      extensor muscles. Vital capacity did not improve on treatment. 

PMID- 24685125
TI  - An Interpretative Phenomenological Analysis of the lived experience of multiple
      concurrent symptoms in patients with lung cancer: a contribution to the study of
      symptom clusters.
AB  - PURPOSE OF THE RESEARCH: To explore the lived experience of multiple concurrent
      symptoms in people with advanced lung cancer to contribute to the understanding
      of the experience of symptom clusters. METHODS AND SAMPLE: Purposive sampling
      recruited ten people with advanced lung cancer who were experiencing three or
      more concurrent symptoms, were at least 18 years of age and were able to provide
      written informed consent. The participants took part in two consecutive, in-depth
      interviews, 3-5 weeks apart. Interpretative Phenomenological Analysis was used to
      analyse the data. FINDINGS: Participants experienced 4-11 concurrent symptoms
      with fatigue, cough, pain and breathlessness featuring prominently in their
      interviews. The participants commonly identified associations between the
      symptoms that they experienced, with the occurrence of one symptom often used to
      explain the occurrence of another. Reductions in physical and social functioning
      were often associated with the experience of multiple concurrent symptoms,
      particularly at times of high symptom severity. The participants' highlighted
      breathlessness and cough as being of particular salience, due to the association
      of these symptoms with fear of death and visibility and embarrassment in public.
      CONCLUSIONS: People with lung cancer experience multiple concurrent symptoms and
      perceive relationships between the symptoms experienced. Within the experience of
      multiple symptoms, people with lung cancer highlight individual symptoms that are
      of particular importance, based on their concomitant meanings. Such findings
      provide vital information for the future development of meaning-based symptom
      cluster interventions.

PMID- 24685126
TI  - The distribution of DNA damage is defined by region-specific susceptibility to
      DNA damage formation rather than repair differences.
AB  - The cellular genomes are continuously damaged by reactive oxygen species (ROS)
      from aerobic processes. The impact of DNA damage depends on the specific site as
      well as the cellular state. The steady-state level of DNA damage is the net
      result of continuous formation and subsequent repair, but it is unknown to what
      extent heterogeneous damage distribution is caused by variations in formation or
      repair of DNA damage. Here, we used a restriction enzyme/qPCR based method to
      analyze DNA damage in promoter and coding regions of four nuclear genes: the two
      house-keeping genes Gadph and Tbp, and the Ndufa9 and Ndufs2 genes encoding
      mitochondrial complex I subunits, as well as mt-Rnr1 encoded by mitochondrial DNA
      (mtDNA). The distribution of steady-state levels of damage varied in a site
      specific manner. Oxidative stress induced damage in nDNA to a similar extent in
      promoter and coding regions, and more so in mtDNA. The subsequent removal of
      damage from nDNA was efficient and comparable with recovery times depending on
      the initial damage load, while repair of mtDNA was delayed with subsequently
      slower repair rate. The repair was furthermore found to be independent of
      transcription or the transcription-coupled repair factor CSB, but dependent on
      cellular ATP. Our results demonstrate that the capacity to repair DNA is
      sufficient to remove exogenously induced damage. Thus, we conclude that the
      heterogeneous steady-state level of DNA damage in promoters and coding regions is
      caused by site-specific DNA damage/modifications that take place under normal
      metabolism.

PMID- 24685127
TI  - Assessment of regional non-linear tissue deformation and air volume change of
      human lungs via image registration.
AB  - We evaluate the non-linear characteristics of the human lung via image
      registration-derived local variables based on volumetric multi-detector-row
      computed tomographic (MDCT) lung image data of six normal human subjects acquired
      at three inflation levels: 20% of vital capacity (VC), 60% VC and 80% VC. Local
      variables include Jacobian (ratio of volume change) and maximum shear strain for
      assessment of lung deformation, and air volume change for assessment of air
      distribution. First, the variables linearly interpolated between 20% and 80% VC
      images to reflect deformation from 20% to 60% VC are compared with those of
      direct registration of 20% and 60% VC images. The result shows that the linearly
      interpolated variables agree only qualitatively with those of registration
      (P<0.05). Then, a quadratic (or linear) interpolation is introduced to link local
      variables to global air volumes of three images (or 20% and 80% VC images). A
      sinusoidal breathing waveform is assumed for assessing the time rate of change of
      these variables. The results show significant differences between two-image and
      three-image results (P<0.05). The three-image results for the whole lung indicate
      that the peak of the maximum shear rate occurs at about 37% of the maximum volume
      difference between 20% and 80% VC, while the peaks for the Jacobian and flow rate
      occur at 50%. This is in agreement with accepted physiology whereby lung tissues
      deform more at lower lung volumes due to lower elasticity and greater compliance.
      Furthermore, the three-image results show that the upper and middle lobes, even
      in the recumbent, supine posture, reach full expansion earlier than the lower
      lobes. 

PMID- 24685128
TI  - Leucine supplementation differentially enhances pancreatic cancer growth in lean
      and overweight mice.
AB  - BACKGROUND: The risk of pancreatic cancer, the 4th deadliest cancer for both men
      and women in the United States, is increased by obesity. Calorie restriction (CR)
      is a well-known dietary regimen that prevents or reverses obesity and suppresses
      tumorigenesis in a variety of animal models, at least in part via inhibition of
      mammalian target of rapamycin (mTOR) signaling. Branched-chain amino acids
      (BCAA), especially leucine, activate mTOR and enhance growth and proliferation of
      myocytes and epithelial cells, which is why leucine is a popular supplement among
      athletes. Leucine is also increasingly being used as a treatment for pancreatic
      cancer cachexia, but the effects of leucine supplementation on pancreatic tumor
      growth have not been elucidated. RESULTS: Supplementation with leucine increased
      pancreatic tumor growth in both lean (104 +/- 17 mm3 versus 46 +/- 13 mm3; P
      <0.05) and overweight (367 +/- 45 mm3 versus 230 +/- 39 mm3; P <0.01) mice, but
      tumor enhancement was associated with different biological outcomes depending on
      the diet. In the lean mice, leucine increased phosphorylation of mTOR and
      downstream effector S6 ribosomal protein, but in the overweight mice, leucine
      reduced glucose clearance and thus increased the amount of circulating glucose
      available to the tumor. CONCLUSIONS: These findings show that leucine
      supplementation enhances tumor growth in both lean and overweight mice through
      diet-dependent effects in a murine model of pancreatic cancer, suggesting caution
      against the clinical use of leucine supplementation for the purposes of skeletal
      muscle enhancement in cachectic patients.

PMID- 24685129
TI  - Quantifying genome-editing outcomes at endogenous loci with SMRT sequencing.
AB  - Targeted genome editing with engineered nucleases has transformed the ability to
      introduce precise sequence modifications at almost any site within the genome. A
      major obstacle to probing the efficiency and consequences of genome editing is
      that no existing method enables the frequency of different editing events to be
      simultaneously measured across a cell population at any endogenous genomic locus.
      We have developed a method for quantifying individual genome-editing outcomes at
      any site of interest with single-molecule real-time (SMRT) DNA sequencing. We
      show that this approach can be applied at various loci using multiple engineered
      nuclease platforms, including transcription-activator-like effector nucleases
      (TALENs), RNA-guided endonucleases (CRISPR/Cas9), and zinc finger nucleases
      (ZFNs), and in different cell lines to identify conditions and strategies in
      which the desired engineering outcome has occurred. This approach offers a
      technique for studying double-strand break repair, facilitates the evaluation of
      gene-editing technologies, and permits sensitive quantification of editing
      outcomes in almost every experimental system used.

PMID- 24685130
TI  - A humanized mouse identifies the bone marrow as a niche with low therapeutic IgG
      activity.
AB  - Genetic differences between humans and in vivo model systems, including mice and
      nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G
      (IgG) activity in humans and understand the molecular and cellular mechanisms
      underlying that activity. To bridge this gap, we established a small-animal model
      system that allowed us to study human IgG effector functions in the context of an
      intact human immune system without the interference of murine Fcgamma receptors
      expressed on mouse innate immune effector cells in vivo. Using a model of B cell
      depletion with different human IgG variants that recognize CD20, we show that
      this humanized mouse model can provide unique insights into the mechanism of
      human IgG activity in vivo. Importantly, these studies identify the bone marrow
      as a niche with low therapeutic IgG activity.

PMID- 24685131
TI  - The APC network regulates the removal of mutated cells from colonic crypts.
AB  - Self-renewal is essential for multicellular organisms but carries the risk of
      somatic mutations that can lead to cancer, which is particularly critical for
      rapidly renewing tissues in a highly mutagenic environment such as the intestinal
      epithelium. Using computational modeling and in vivo experimentation, we have
      analyzed how adenomatous polyposis coli (APC) mutations and beta-catenin
      aberrations affect the maintenance of mutant cells in colonic crypts. The
      increasing abundance of APC along the crypt axis forms a gradient of cellular
      adhesion that causes more proliferative cells to accelerate their movement toward
      the top of the crypt, where they are shed into the lumen. Thus, the normal crypt
      can efficiently eliminate beta-catenin mutant cells, whereas APC mutations favor
      retention. Together, the molecular design of the APC/beta-catenin signaling
      network integrates cell proliferation and migration dynamics to translate
      intracellular signal processing and protein gradients along the crypt into
      intercellular interactions and whole-crypt physiological or pathological
      behavior.

PMID- 24685132
TI  - Intrinsic resistance to MEK inhibition in KRAS mutant lung and colon cancer
      through transcriptional induction of ERBB3.
AB  - There are no effective therapies for the ~30% of human malignancies with mutant
      RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that
      suppression of the ERBB3 receptor tyrosine kinase sensitizes KRAS mutant lung and
      colon cancer cells to MEK inhibitors. We show that MEK inhibition results in MYC
      dependent transcriptional upregulation of ERBB3, which is responsible for
      intrinsic drug resistance. Drugs targeting both EGFR and ERBB2, each capable of
      forming heterodimers with ERBB3, can reverse unresponsiveness to MEK inhibition
      by decreasing inhibitory phosphorylation of the proapoptotic proteins BAD and
      BIM. Moreover, ERBB3 protein level is a biomarker of response to combinatorial
      treatment. These data suggest a combination strategy for treating KRAS mutant
      colon and lung cancers and a way to identify the tumors that are most likely to
      benefit from such combinatorial treatment.

PMID- 24685133
TI  - Autophagy controls the kinetics and extent of mitochondrial apoptosis by
      regulating PUMA levels.
AB  - Macroautophagy is thought to protect against apoptosis; however, underlying
      mechanisms are poorly understood. We examined how autophagy affects canonical
      death receptor-induced mitochondrial outer membrane permeabilization (MOMP) and
      apoptosis. MOMP occurs at variable times in a population of cells, and this is
      delayed by autophagy. Additionally, autophagy leads to inefficient MOMP, after
      which some cells die through a slower process than typical apoptosis and,
      surprisingly, can recover and divide afterward. These effects are associated with
      p62/SQSTM1-dependent selective autophagy causing PUMA levels to be kept low
      through an indirect mechanism whereby autophagy affects constitutive levels of
      PUMA mRNA. PUMA depletion is sufficient to prevent the sensitization to apoptosis
      that occurs when autophagy is blocked. Autophagy can therefore control apoptosis
      via a key regulator that makes MOMP faster and more efficient, thus ensuring
      rapid completion of apoptosis. This identifies a molecular mechanism whereby cell
      fate decisions can be determined by autophagy. 

PMID- 24685135
TI  - Polarized expression of p75(NTR) specifies axons during development and adult
      neurogenesis.
AB  - VIDEO ABSTRACT: Newly generated neurons initiate polarizing signals that specify
      a single axon and multiple dendrites, a process critical for patterning neuronal
      circuits in vivo. Here, we report that the pan-neurotrophin receptor p75(NTR) is
      a polarity regulator that localizes asymmetrically in differentiating neurons in
      response to neurotrophins and is required for specification of the future axon.
      In cultured hippocampal neurons, local exposure to neurotrophins causes early
      accumulation of p75(NTR) into one undifferentiated neurite to specify axon fate.
      Moreover, knockout or knockdown of p75(NTR) results in failure to initiate an
      axon in newborn neurons upon cell-cycle exit in vitro and in the developing
      cortex, as well as during adult hippocampal neurogenesis in vivo. Hence, p75(NTR)
      governs neuronal polarity, determining pattern and assembly of neuronal circuits
      in adult hippocampus and cortical development.

PMID- 24685134
TI  - Iron metabolism regulates p53 signaling through direct heme-p53 interaction and
      modulation of p53 localization, stability, and function.
AB  - Iron excess is closely associated with tumorigenesis in multiple types of human
      cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has
      emerged as a major strategy for chemotherapy, but it exerts tumor suppression
      only on select human malignancies. Here, we report that the tumor suppressor
      protein p53 is downregulated during iron excess. Strikingly, the iron
      polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions,
      and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a
      tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor
      growth, suggesting that upregulation of wild-type p53 signaling underlies the
      selective efficacy of iron deprivation. Our findings thus identify a direct link
      between iron/heme homeostasis and the regulation of p53 signaling, which not only
      provides mechanistic insights into iron-excess-associated tumorigenesis but may
      also help predict and improve outcomes in iron-deprivation-based chemotherapy. 

PMID- 24685136
TI  - The homeodomain transcription factor Hb9 controls axon guidance in Drosophila
      through the regulation of Robo receptors.
AB  - Transcription factors establish neural diversity and wiring specificity; however,
      how they orchestrate changes in cell morphology remains poorly understood. The
      Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how
      their precise expression domains are established is unknown. Here, we show that
      the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to
      regulate axon guidance in the Drosophila embryo. In ventrally projecting motor
      neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in
      hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor
      domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can
      regulate the medio-lateral position of axons through robo2 and robo3, and
      restoring robo3 expression in hb9 mutants rescues the lateral position defects of
      a subset of neurons. Altogether, these data identify Robo2 and Robo3 as key
      effectors of Hb9 in regulating nervous system development.

PMID- 24685137
TI  - A histone methylation network regulates transgenerational epigenetic memory in C.
      elegans.
AB  - How epigenetic information is transmitted from generation to generation remains
      largely unknown. Deletion of the C. elegans histone H3 lysine 4 dimethyl
      (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic
      H3K4me2 mark and progressive decline in fertility. Here, we identified multiple
      chromatin-modifying factors, including H3K4me1/me2 and H3K9me3
      methyltransferases, an H3K9me3 demethylase, and an H3K9me reader, which either
      suppress or accelerate the progressive transgenerational phenotypes of spr-5
      mutant worms. Our findings uncover a network of chromatin regulators that control
      the transgenerational flow of epigenetic information and suggest that the balance
      between euchromatic H3K4 and heterochromatic H3K9 methylation regulates
      transgenerational effects on fertility.

PMID- 24685138
TI  - The distribution of genomic variations in human iPSCs is related to replication
      timing reorganization during reprogramming.
AB  - Cell-fate change involves significant genome reorganization, including changes in
      replication timing, but how these changes are related to genetic variation has
      not been examined. To study how a change in replication timing that occurs during
      reprogramming impacts the copy-number variation (CNV) landscape, we generated
      genome-wide replication-timing profiles of induced pluripotent stem cells (iPSCs)
      and their parental fibroblasts. A significant portion of the genome changes
      replication timing as a result of reprogramming, indicative of overall genome
      reorganization. We found that early- and late-replicating domains in iPSCs are
      differentially affected by copy-number gains and losses and that in particular,
      CNV gains accumulate in regions of the genome that change to earlier replication
      during the reprogramming process. This differential relationship was present
      irrespective of reprogramming method. Overall, our findings reveal a functional
      association between reorganization of replication timing and the CNV landscape
      that emerges during reprogramming. 

PMID- 24685139
TI  - Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7.
AB  - The Rif1 protein, originally identified as a telomere-binding factor in yeast,
      has recently been implicated in DNA replication control from yeast to metazoans.
      Here, we show that budding yeast Rif1 protein inhibits activation of
      prereplication complexes (pre-RCs). This inhibitory function requires two N
      terminal motifs, RVxF and SILK, associated with recruitment of PP1 phosphatase
      (Glc7). In G1 phase, we show both that Glc7 interacts with Rif1 in an RVxF/SILK
      dependent manner and that two proteins implicated in pre-RC activation, Mcm4 and
      Sld3, display increased Dbf4-dependent kinase (DDK) phosphorylation in rif1
      mutants. Rif1 also interacts with Dbf4 in yeast two-hybrid assays, further
      implicating this protein in direct modulation of pre-RC activation through the
      DDK. Finally, we demonstrate Rif1 RVxF/SILK motif-dependent recruitment of Glc7
      to telomeres and earlier replication of these regions in cells where the motifs
      are mutated. Our data thus link Rif1 to negative regulation of replication origin
      firing through recruitment of the Glc7 phosphatase.

PMID- 24685141
TI  - Long-term results of radiotherapy in anaplastic thyroid cancer.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is an aggressive malignant tumour
      with a poor prognosis. The median overall survival is described in the literature
      to be just 6 months, however, in series of selected patients treated by
      multimodal therapy cases of long-time-survival have been reported. We analyzed
      the role of radiotherapy and the impact of other therapies and clinical features
      on survival in patients with ATC. METHODS: In a retrospective analysis of all
      patients (n = 40), who presented with histologically proven ATC at a single
      centre between 1989 and 2008, patient and treatment characteristics with a focus
      on details of radiotherapy were registered and the survival status determined.
      RESULTS: 39 of 40 patients received radiotherapy, 80% underwent surgery and 15%
      had chemotherapy. The median dosis of radiation was 50 Gy (6-60.4 Gy), in 87.5%
      fractionation was once daily. In 49.4% opposing-field techniques were applied, in
      14% 3D-conformal-techniques and 32.5% combinations of both.The median overall
      survival (OS) was 5 months, 1-year survival 35.2% and 5-year-survival 21.6%.
      Interestingly, 24.3% survived 2 years or longer. Three factors could be
      identified as predictors of improved overall survival: absence of lymph node
      metastasis (N0) (median OS 18.3 months), median dose of radiation of 50 Gy or
      more (median OS 10.5 months) and the use of any surgery (median OS 10.5 months).
      CONCLUSIONS: Despite the generally poor outcome, the combination of surgery and
      intensive radiotherapy can result in long-term survival in selected patients with
      ATC.

PMID- 24685140
TI  - Inhibition of ATPIF1 ameliorates severe mitochondrial respiratory chain
      dysfunction in mammalian cells.
AB  - Mitochondrial respiratory chain disorders are characterized by loss of electron
      transport chain (ETC) activity. Although the causes of many such diseases are
      known, there is a lack of effective therapies. To identify genes that confer
      resistance to severe ETC dysfunction when inactivated, we performed a genome-wide
      genetic screen in haploid human cells with the mitochondrial complex III
      inhibitor antimycin. This screen revealed that loss of ATPIF1 strongly protects
      against antimycin-induced ETC dysfunction and cell death by allowing for the
      maintenance of mitochondrial membrane potential. ATPIF1 loss protects against
      other forms of ETC dysfunction and is even essential for the viability of human
      rho degrees  cells lacking mitochondrial DNA, a system commonly used for studying
      ETC dysfunction. Importantly, inhibition of ATPIF1 ameliorates complex III
      blockade in primary hepatocytes, a cell type afflicted in severe mitochondrial
      disease. Altogether, these results suggest that inhibition of ATPIF1 can
      ameliorate severe ETC dysfunction in mitochondrial pathology.

PMID- 24685142
TI  - Cortistatin-14 mediates its anticonvulsant effects via sst2 and sst3 but not
      ghrelin receptors.
AB  - Cortistatin (CST)-14, a neuropeptide that is structurally and functionally
      related to somatostatin-14 (SRIF) binds all five somatostatin receptor subtypes
      (sst1-sst5). Using in vivo microdialysis and telemetry-based
      electroencephalographic recordings, we provide the first experimental evidence
      for anticonvulsive effects of CST-14 in a pilocarpine-induced seizure model in
      rats and mice and for the involvement of sst2 and sst3 receptors in these
      anticonvulsant actions of CST-14. Both receptor subtypes are required for the
      anticonvulsant effects of CST-14 given that co-perfusion of a selective sst2
      antagonist (cyanamid15486) or a selective sst3 antagonist (SST3-ODN-8) reversed
      anticonvulsant effect of CST-14, and this, independently of each other. Next, as
      the ghrelin receptor has been proposed as a target for the biological effects of
      CST-14, we used ghrelin receptor knockout mice and their wild type littermates to
      study the involvement of this receptor in the anticonvulsive actions of CST-14.
      Our results show a significant decrease in seizure duration in both genotypes
      when CST-14 treated mice were compared with corresponding control animals
      receiving only pilocarpine. In addition, this CST-14-induced decrease was
      comparable in both genotypes. We here thus provide the first evidence that
      ghrelin receptors are not involved in mediating anticonvulsant actions of CST-14
      in vivo.

PMID- 24685143
TI  - Which psychosocial factors best predict cognitive performance in older adults?
AB  - Negative affect (e.g., depression) is associated with accelerated age-related
      cognitive decline and heightened dementia risk. Fewer studies examine positive
      psychosocial factors (e.g., emotional support, self-efficacy) in cognitive aging.
      Preliminary reports suggest that these variables predict slower cognitive decline
      independent of negative affect. No reports have examined these factors in a
      single model to determine which best relate to cognition. Data from 482
      individuals 55 and older came from the normative sample for the NIH Toolbox for
      the Assessment of Neurological and Behavioral Function. Negative and positive
      psychosocial factors, executive functioning, working memory, processing speed,
      and episodic memory were measured with the NIH Toolbox Emotion and Cognition
      modules. Confirmatory factor analysis and structural equation modeling
      characterized independent relations between psychosocial factors and cognition.
      Psychosocial variables loaded onto negative and positive factors. Independent of
      education, negative affect and health status, greater emotional support was
      associated with better task-switching and processing speed. Greater self-efficacy
      was associated with better working memory. Negative affect was not independently
      associated with any cognitive variables. Findings support the conceptual
      distinctness of negative and positive psychosocial factors in older adults.
      Emotional support and self-efficacy may be more closely tied to cognition than
      other psychosocial variables.

PMID- 24685145
TI  - Structural basis of substrate specificity of human oligosaccharyl transferase
      subunit N33/Tusc3 and its role in regulating protein N-glycosylation.
AB  - N-linked glycosylation of proteins in the endoplasmic reticulum (ER) is essential
      in eukaryotes and catalyzed by oligosaccharyl transferase (OST). Human OST is a
      hetero-oligomer of seven subunits. The subunit N33/Tusc3 is a tumor suppressor
      candidate, and defects in the subunit N33/Tusc3 are linked with nonsyndromic
      mental retardation. Here, we show that N33/Tusc3 possesses a membrane-anchored N
      terminal thioredoxin domain located in the ER lumen that may form transient mixed
      disulfide complexes with OST substrates. X-ray structures of complexes between
      N33/Tusc3 and two different peptides as model substrates reveal a defined peptide
      binding groove adjacent to the active site that can accommodate peptides in
      opposite orientations. Structural and biochemical data show that N33/Tusc3
      prefers peptides bearing a hydrophobic residue two residues away from the
      cysteine forming the mixed disulfide with N33/Tusc3. Our results support a model
      in which N33/Tusc3 increases glycosylation efficiency for a subset of human
      glycoproteins by slowing glycoprotein folding. 

PMID- 24685144
TI  - Rapid onset of cardiomyopathy in STZ-induced female diabetic mice involves the
      downregulation of pro-survival Pim-1.
AB  - BACKGROUND: Diabetic women are five times more likely to develop congestive heart
      failure compared with two fold for men. The underlying mechanism for this gender
      difference is not known. Here we investigate the molecular mechanisms responsible
      for this female disadvantage and attempt safeguarding cardiomyocytes viability
      and function through restoration of pro-survival Pim-1. METHODS AND RESULTS:
      Diabetes was induced by injection of streptozotocin in CD1 mice of both genders.
      Functional and dimensional parameters measurement using echocardiography revealed
      diastolic dysfunction in female diabetic mice within 8 weeks after STZ-induced
      diabetes. This was associated with significant downregulation of pro-survival Pim
      1 and upregulation of pro-apoptotic Caspase-3, microRNA-1 and microRNA-208a. Male
      diabetic mice did not show any significant changes at this time point (P < 0.05
      vs. female diabetic). Further, the onset of ventricular remodelling was quicker
      in female diabetic mice showing marked left ventricular dilation, reduced
      ejection fraction and poor contractility (P < 0.05 vs. male diabetic at 12 and 16
      weeks of STZ-induced diabetes). Molecular analysis of samples from human diabetic
      hearts confirmed the results of pre-clinical studies, showing marked
      downregulation of Pim-1 in the female diabetic heart (P < 0.05 vs. male
      diabetic). Finally, in vitro restoration of Pim-1 reversed the female
      disadvantage in diabetic cardiomyocytes. CONCLUSIONS: We provide novel insights
      into the molecular mechanisms behind the rapid onset of cardiomyopathy in female
      diabetics. These results suggest the requirement for the development of gender
      specific treatments for diabetic cardiomyopathy.

PMID- 24685146
TI  - Identification of an actin binding surface on vinculin that mediates mechanical
      cell and focal adhesion properties.
AB  - Vinculin, a cytoskeletal scaffold protein essential for embryogenesis and
      cardiovascular function, localizes to focal adhesions and adherens junctions,
      connecting cell surface receptors to the actin cytoskeleton. While vinculin
      interacts with many adhesion proteins, its interaction with filamentous actin
      regulates cell morphology, motility, and mechanotransduction. Disruption of this
      interaction lowers cell traction forces and enhances actin flow rates. Although a
      model for the vinculin:actin complex exists, we recently identified actin-binding
      deficient mutants of vinculin outside sites predicted to bind actin and developed
      an alternative model to better define this actin-binding surface, using negative
      stain electron microscopy (EM), discrete molecular dynamics, and mutagenesis.
      Actin-binding deficient vinculin variants expressed in vinculin knockout
      fibroblasts fail to rescue cell-spreading defects and reduce cellular response to
      external force. These findings highlight the importance of this actin-binding
      surface and provide the molecular basis for elucidating additional roles of this
      interaction, including actin-induced conformational changes that promote actin
      bundling. 

PMID- 24685147
TI  - Distinct docking and stabilization steps of the Pseudopilus conformational
      transition path suggest rotational assembly of type IV pilus-like fibers.
AB  - The closely related bacterial type II secretion (T2S) and type IV pilus (T4P)
      systems are sophisticated machines that assemble dynamic fibers promoting protein
      transport, motility, or adhesion. Despite their essential role in virulence, the
      molecular mechanisms underlying helical fiber assembly remain unknown. Here, we
      use electron microscopy and flexible modeling to study conformational changes of
      PulG pili assembled by the Klebsiella oxytoca T2SS. Neural network analysis of
      3,900 pilus models suggested a transition path toward low-energy conformations
      driven by progressive increase in fiber helical twist. Detailed predictions of
      interprotomer contacts along this path were tested by site-directed mutagenesis,
      pilus assembly, and protein secretion analyses. We demonstrate that electrostatic
      interactions between adjacent protomers (P-P+1) in the membrane drive pseudopilin
      docking, while P-P+3 and P-P+4 contacts determine downstream fiber stabilization
      steps. These results support a model of a spool-like assembly mechanism for
      fibers of the T2SS-T4P superfamily. 

PMID- 24685148
TI  - Structural basis for proteasome formation controlled by an assembly chaperone
      nas2.
AB  - Proteasome formation does not occur due to spontaneous self-organization but
      results from a highly ordered process assisted by several assembly chaperones.
      The assembly of the proteasome ATPase subunits is assisted by four client
      specific chaperones, of which three have been structurally resolved. Here, we
      provide the structural basis for the working mechanisms of the last, hereto
      structurally uncharacterized assembly chaperone, Nas2. We revealed that Nas2
      binds to the Rpt5 subunit in a bivalent mode: the N-terminal helical domain of
      Nas2 masks the Rpt1-interacting surface of Rpt5, whereas its C-terminal PDZ
      domain caps the C-terminal proteasome-activating motif. Thus, Nas2 operates as a
      proteasome activation blocker, offering a checkpoint during the formation of the
      19S ATPase prior to its docking onto the proteolytic 20S core particle. 

PMID- 24685149
TI  - Is provider type associated with cancer screening and prevention: advanced
      practice registered nurses, physician assistants, and physicians.
AB  - BACKGROUND: Physician recommendations for cancer screening and prevention are
      associated with patient compliance. However, time constraints may limit
      physicians' ability to provide all recommended preventive services, especially
      with increasing demand from the Affordable Care Act in the United States. Team
      based practice that includes advanced practice registered nurses and physician
      assistants (APRN/PA) may help meet this demand. This study investigates the
      relationship between an APRN/PA visit and receipt of guideline-consistent cancer
      screening and prevention recommendations. METHODS: Data from the 2010 National
      Health Interview Survey were analyzed with multivariate logistic regression to
      assess provider type seen and receipt of guideline-consistent cancer screening
      and prevention recommendations (n = 26,716). RESULTS: In adjusted analyses, women
      who saw a primary care physician (PCP) and an APRN/PA or a PCP without an APRN/PA
      in the past 12 months were more likely to be compliant with cervical and breast
      cancer screening guidelines than women who did not see a PCP or APRN/PA (all p <
      0.0001 for provider type). Women and men who saw a PCP and an APRN/PA or a PCP
      without an APRN/PA were also more likely to receive guideline consistent
      colorectal cancer screening and advice to quit smoking and participate in
      physical activity than women and men who did not see a PCP or APRN/PA (all p <
      0.01 for provider type). CONCLUSIONS: Seeing a PCP alone, or in conjunction with
      an APRN/PA is associated with patient receipt of guideline-consistent cancer
      prevention and screening recommendations. Integrating APRN/PA into primary care
      may assist with the delivery of cancer prevention and screening services. More
      intervention research efforts are needed to explore how APRN/PA will be best able
      to increase cancer screening, HPV vaccination, and receipt of behavioral
      counseling, especially during this era of healthcare reform.

PMID- 24685151
TI  - Optimisation of the synthesis of vancomycin-selective molecularly imprinted
      polymer nanoparticles using automatic photoreactor.
AB  - A novel optimized protocol for solid-state synthesis of molecularly imprinted
      polymer nanoparticles (nanoMIPs) with specificity for antibiotic vancomycin is
      described. The experimental objective was optimization of the synthesis
      parameters (factors) affecting the yield of obtained nanoparticles which have
      been synthesized using the first prototype of an automated solid-phase
      synthesizer. Applications of experimental design (or design of experiments) in
      optimization of nanoMIP yield were carried out using MODDE 9.0 software. The
      factors chosen in the model were the amount of functional monomers in the
      polymerization mixture, irradiation time, temperature during polymerization, and
      elution temperature. In general, it could be concluded that the irradiation time
      is the most important and the temperature was the least important factor which
      influences the yield of nanoparticles. Overall, the response surface methodology
      proved to be an effective tool in reducing time required for optimization of
      complex experimental conditions. 

PMID- 24685150
TI  - Comparative efficacy of a multi-epitope DNA vaccine via intranasal, peroral, and
      intramuscular delivery against lethal Toxoplasma gondii infection in mice.
AB  - BACKGROUND: Toxoplasmosis is an important zoonosis, being a cause of congenital
      disease and abortion in animals and humans. DNA vaccination as a promising
      vaccine remains a challenge for an improved delivery system. METHODS: In this
      study, attenuated Salmonella typhimurium BRD509 was used to deliver a DNA vaccine
      encoding several epitopes, derived from the tachyzoite proteins SAG1, GRA1, ROP2,
      GRA4 and bradyzoite proteins SAG2C, SAG2X of Toxoplasma gondii and A2/B subunit
      of cholera toxin. The recombinant plasmids were electroporated into attenuated
      Salmonella typhimurium. Humoral and cellular immune responses were evaluated for
      BALB/c mice administered with this attenuated recombinant Salmonella vaccine via
      the oral and nasal route or by intramuscular injection with DNA plasmid directly.
      RESULTS: High IgG levels were present in the mice immunized intramuscularly,
      while IgA levels were higher in the oral and nasal immunization groups.
      Furthermore, cellular immunity was activated in oral immunization groups with 60%
      survival rate following challenge with high virulent RH strain. CONCLUSIONS: The
      results from this study indicate that a DNA vaccine encoding multi-epitopes of T.
      gondii delivered by attenuated Salmonella is promising.

PMID- 24685152
TI  - Proton therapy expansion under current United States reimbursement models.
AB  - PURPOSE: To determine whether all the existing and planned proton beam therapy
      (PBT) centers in the United States can survive on a local patient mix that is
      dictated by insurers, not by number of patients. METHODS AND MATERIALS: We
      determined current and projected cancer rates for 10 major US metropolitan areas.
      Using published utilization rates, we calculated patient percentages who are
      candidates for PBT. Then, on the basis of current published insurer coverage
      policies, we applied our experience of what would be covered to determine the net
      number of patients for whom reimbursement is expected. Having determined the net
      number of covered patients, we applied our average beam delivery times to
      determine the total number of minutes needed to treat that patient over the
      course of their treatment. We then calculated our expected annual patient
      capacity per treatment room to determine the appropriate number of treatment
      rooms for the area. RESULTS: The population of patients who will be both PBT
      candidates and will have treatments reimbursed by insurance is significantly
      smaller than the population who should receive PBT. Coverage decisions made by
      insurers reduce the number of PBT rooms that are economically viable.
      CONCLUSIONS: The expansion of PBT centers in the US is not sustainable under the
      current reimbursement model. Viability of new centers will be limited to those
      operating in larger regional metropolitan areas, and few metropolitan areas in
      the US can support multiple centers. In general, 1-room centers require captive
      (non-PBT-served) populations of approximately 1,000,000 lives to be economically
      viable, and a large center will require a population of >4,000,000 lives. In
      areas with smaller populations or where or a PBT center already exists, new
      centers require subsidy.

PMID- 24685153
TI  - Perceptions of radiation oncologists and urologists on sources and type of
      evidence to inform prostate cancer treatment decisions.
AB  - PURPOSE: To perform a national survey of radiation oncologists and urologists
      about the type of resources used and the level of evidence needed to change
      clinical practice in localized prostate cancer. METHODS AND MATERIALS: From a
      random sample, 1422 physicians were mailed a survey assessing the types of
      information used and what level of evidence could alter their clinical practice
      in prostate cancer. Multivariable logistic regression models were used to
      identify differences in physician characteristics for each outcome. RESULTS:
      Survey response rates were similar for radiation oncologists and urologists (44%
      vs 46%; P=.46). Specialty-specific journals represented the most commonly used
      resource for informing the clinical practice for radiation oncologists (65%) and
      urologists (70%). Relative to radiation oncologists, urologists were less likely
      to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio
      [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P<.001) but
      more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006).
      Both radiation oncologists and urologists most commonly reported large
      randomized, clinical trials as the level of evidence to change treatment
      recommendations for localized prostate cancer (85% vs 77%; P=.009). CONCLUSIONS:
      Both specialties rely on their own specialty-specific journals and view
      randomized, clinical trials as the level of evidence needed to change clinical
      practice. Our study provides a context on meaningful ways of disseminating
      evidence for localized prostate cancer.

PMID- 24685154
TI  - Treatment of head and neck paragangliomas with external beam radiation therapy.
AB  - PURPOSE: To retrospectively assess the outcomes of radiation therapy in patients
      with head and neck paragangliomas. METHODS AND MATERIALS: From 1990 to 2009, 66
      patients with 81 head and neck paragangliomas were treated by conventional
      external beam radiation therapy in 25 fractions at a median dose of 45 Gy (range,
      41.4-68 Gy). One case was malignant. The median gross target volume and planning
      target volume were 30 cm(3) (range, 0.9-243 cm(3)) and 116 cm(3) (range, 24-731
      cm(3)), respectively. Median age was 57.4 years (range, 15-84 years). Eleven
      patients had multicentric lesions, and 8 had family histories of paraganglioma.
      Paragangliomas were located in the temporal bone, the carotid body, and the
      glomus vagal in 51, 18, and 10 patients, respectively. Forty-six patients had
      exclusive radiation therapy, and 20 had salvage radiation therapy. The median
      follow-up was 4.1 years (range, 0.1-21.2 years). RESULTS: One patient had a
      recurrence of temporal bone paraganglioma 8 years after treatment. The actuarial
      local control rates were 100% at 5 years and 98.7% at 10 years. Patients with
      multifocal tumors and family histories were significantly younger (42 years vs 58
      years [P=.002] and 37 years vs 58 years [P=.0003], respectively). The association
      between family predisposition and multifocality was significant (P<.001). Two
      patients had cause-specific death within the 6 months after irradiation. During
      radiation therapy, 9 patients required hospitalization for weight loss, nausea,
      mucositis, or ophthalmic zoster. Two late vascular complications occurred (middle
      cerebral artery and carotid stenosis), and 2 late radiation-related meningiomas
      appeared 15 and 18 years after treatment. CONCLUSION: Conventional external beam
      radiation therapy is an effective and safe treatment option that achieves
      excellent local control; it should be considered as a first-line treatment of
      choice for head and neck paragangliomas.

PMID- 24685155
TI  - Combined portal vein resection in the treatment of hilar cholangiocarcinoma: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To analyse the efficacy and safety of portal vein resection for hilar
      cholangiocarcinoma (HCCA). METHODS: A thorough search of PubMed, the Cochrane
      Library, Embase, the Chinese BioMedical Literature (CBM), and the Chinese Medical
      Current Contents (CMCC) databases was performed to identify comparative studies
      concerning combined portal vein resection (PVR) versus surgery without portal
      vein resection (Without PVR) and no surgical tumour resection (NR) in the
      treatment of HCCA. RESULTS: Thirteen studies with a total of 1921 HCCA cases were
      included. The results of the meta-analysis revealed that PVR was associated with
      a poorer overall survival than Without PVR (HR = 1.90; 95%CI 1.59-2.28; P <
      0.00001) but was significantly better than NR (HR = 0.33; 95%CI 0.26-0.41; P <
      0.00001). The PVR group exhibited significantly higher rates of advanced disease
      and a higher proportion of lymph node metastasis (OR = 1.50; 95%CI 1.06-2.13; P =
      0.02) and perineural invasion (OR = 2.95; 95%CI 1.80-4.84; P < 0.0001), and the
      PVR group exhibited a lower curative resection rate (OR = 0.65; 95%CI 0.46-0.91;
      P = 0.01). No significant differences were found between the two groups with
      respect to postoperative mortality and morbidity. CONCLUSIONS: Combined PVR is
      safe and feasible in the treatment of HCCA when the portal vein is grossly
      involved. For advanced HCCA when the portal vein is grossly involved, surgical
      resection including PVR can benefit the overall survival in certain patients.
      However, further randomised controlled trials are necessary to determine the
      prognostic effects of the addition of PVR to the surgical procedure.

PMID- 24685156
TI  - Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis,
      treatment and follow-up.

PMID- 24685157
TI  - An mRNA-derived noncoding RNA targets and regulates the ribosome.
AB  - The structural and functional repertoire of small non-protein-coding RNAs
      (ncRNAs) is central for establishing gene regulation networks in cells and
      organisms. Here, we show that an mRNA-derived 18-nucleotide-long ncRNA is capable
      of downregulating translation in Saccharomyces cerevisiae by targeting the
      ribosome. This 18-mer ncRNA binds to polysomes upon salt stress and is crucial
      for efficient growth under hyperosmotic conditions. Although the 18-mer RNA
      originates from the TRM10 locus, which encodes a tRNA methyltransferase, genetic
      analyses revealed the 18-mer RNA nucleotide sequence, rather than the mRNA
      encoded enzyme, as the translation regulator. Our data reveal the ribosome as a
      target for a small regulatory ncRNA and demonstrate the existence of a yet unkown
      mechanism of translation regulation. Ribosome-targeted small ncRNAs are found in
      all domains of life and represent a prevalent but so far largely unexplored class
      of regulatory molecules. 

PMID- 24685158
TI  - Quality control autophagy degrades soluble ERAD-resistant conformers of the
      misfolded membrane protein GnRHR.
AB  - Molecular chaperones triage misfolded proteins via action as substrate selectors
      for quality control (QC) machines that fold or degrade clients. Herein, the
      endoplasmic reticulum (ER)-associated Hsp40 JB12 is reported to participate in
      partitioning mutant conformers of gonadotropin-releasing hormone receptor
      (GnRHR), a G protein-coupled receptor, between ER-associated degradation (ERAD)
      and an ERQC autophagy pathway. ERQC autophagy degrades E90K-GnRHR because pools
      of its partially folded and detergent-soluble degradation intermediates are
      resistant to ERAD. S168R-GnRHR is globally misfolded and disposed of via ERAD,
      but inhibition of p97, the protein retrotranslocation motor, shunts S168R-GnRHR
      from ERAD to ERQC autophagy. Partially folded and grossly misfolded forms of
      GnRHR associate with JB12 and Hsp70. Elevation of JB12 promotes ERAD of S168R
      GnRHR, with E90K-GnRHR being resistant. E90K-GnRHR elicits association of the
      Vps34 autophagy initiation complex with JB12. Interaction between ER-associated
      Hsp40s and the Vps34 complex permits the selective degradation of ERAD-resistant
      membrane proteins via ERQC autophagy. 

PMID- 24685160
TI  - Steady state recycling chromatography with solvent removal-effect of solvent
      removal constraints on process operation under ideal conditions.
AB  - Steady state recycling chromatography (SSR) offers a means to reduce eluent
      consumption and increase productivity in preparative and production scale
      chromatographic separations. Even better performance is obtained with an
      integrated process by coupling solvent removal unit to the chromatographic
      separation unit. Here a design method for SSR with an integrated solvent removal
      unit (SSR-SR) is presented. The method is more practical than previous work as
      the effect of physical constraints, such as solubility or viscosity, imposed on
      the amount of solvent removed is included. The method holds under ideal
      conditions for binary systems with competitive Langmuir isotherm model. The
      design equations allow calculation of the regions of feasible operating
      parameters when either the maximum concentrations in the solvent removal unit or
      of the solution fed into the chromatographic column is restricted. The method was
      applied to analyze the performance of different SSR-SR configurations in two case
      studies: the separation of mandelic acid enantiomers and the separation of EMD
      53986 enantiomers. The benefits of SSR-SR are relatively small under ideal
      conditions but the design method developed here can give a good starting point
      for designing SSR-SR processes under non-ideal conditions. 

PMID- 24685159
TI  - Hormone-responsive enhancer-activity maps reveal predictive motifs, indirect
      repression, and targeting of closed chromatin.
AB  - Steroid hormones act as important developmental switches, and their nuclear
      receptors regulate many genes. However, few hormone-dependent enhancers have been
      characterized, and important aspects of their sequence architecture, cell-type
      specific activating and repressing functions, or the regulatory roles of their
      chromatin structure have remained unclear. We used STARR-seq, a recently
      developed enhancer-screening assay, and ecdysone signaling in two different
      Drosophila cell types to derive genome-wide hormone-dependent enhancer-activity
      maps. We demonstrate that enhancer activation depends on cis-regulatory motif
      combinations that differ between cell types and can predict cell-type-specific
      ecdysone targeting. Activated enhancers are often not accessible prior to
      induction. Enhancer repression following hormone treatment seems independent of
      receptor motifs and receptor binding to the enhancer, as we show using ChIP-seq,
      but appears to rely on motifs for other factors, including Eip74. Our strategy is
      applicable to study signal-dependent enhancers for different pathways and across
      organisms. 

PMID- 24685161
TI  - Comparison of the relative merits of port-location rearrangement and partial
      feeding as the strategy for improving the performances of a three-zone simulated
      moving chromatography for separation of succinic acid and lactic acid.
AB  - The three-zone simulated moving bed (SMB) chromatographic process for separation
      of succinic acid and lactic acid, which has been developed previously, was based
      on a classical port-location arrangement (desorbent->extract->feed->raffinate)
      and a classical feeding mode (full-feeding). To improve the performance of the
      three-zone SMB process, it is worth utilizing the strategy of either a port
      location rearrangement (desorbent->feed->raffinate->extract) or a partial
      feeding. To investigate which of the two strategies is more effective, the three
      zone SMBs based on the port-location rearrangement (PR) and the partial-feeding
      (PF) were optimized each under equal conditions and then the two strategies were
      compared in terms of product purities or throughput. The result showed that the
      PR strategy led to higher purities or higher throughput than the PF strategy in
      regard to the previously reported three-zone SMB system. To check whether such
      trend is still valid in other separation systems, the above optimization works
      were repeated while varying only the selectivity between two feed components. It
      was confirmed that the PR strategy is definitely superior to the PF strategy.
      However, such superiority of the PR over the PF strategy is lessened as the
      selectivity becomes lower. If the selectivity is significantly low, the PR
      strategy is rather outperformed by the PF strategy. 

PMID- 24685163
TI  - Determination of organothiophosphorus pesticides in water by liquid
      chromatography and post-column chemiluminescence with cerium(IV).
AB  - A new, fast, selective and sensitive method has been developed for the
      simultaneous determination of nine organothiophosphorus (OTP) pesticides, namely
      omethoate, dimethoate, disulfoton-sulfoxide, methidathion, phosmet, malathion,
      diazinon, pirimiphos-methyl and chlorpyrifos. The pesticides were separated on a
      Kinetex C18 column by gradient elution with acetonitrile:water. A post-column
      basic hydrolysis of the pesticides and later a chemiluminescence (CL) reaction
      with cerium (IV) in acid medium was carried out. Hexadecylpyridinium chloride
      highly enhanced the CL emission. Under optimized conditions, linearity,
      precision, limits of detection and quantification, and accuracy were determined.
      Both selectivity and sensitivity were compared with those obtained with UV
      detection. In combination with SPE, limits of detection in the range 15-80ng/L
      and 5-30ng/L were obtained when 250mL and 1000mL of solution were treated,
      respectively. When applied to 250mL of sample the inter-day precision of the
      method was between 3.5% and 7.3% and the intra-day precision between 2.9% and
      6.0%. The method was applied to determine OTP pesticides in spiked water samples
      from different origins: irrigation, river, sea, ground, spring, mineral and tap
      waters, being the percentage of recovery of added amounts near 100% form most of
      the pesticides. 

PMID- 24685162
TI  - Fluorescence recovery after photobleaching investigation of protein transport and
      exchange in chromatographic media.
AB  - A fully-mechanistic understanding of protein transport and sorption in
      chromatographic materials has remained elusive despite the application of modern
      continuum and molecular observation techniques. While measuring overall uptake
      rates in proteins in chromatographic media is relatively straightforward,
      quantifying mechanistic contributions is much more challenging. Further, at
      equilibrium in fully-loaded particles, measuring rates of kinetic exchange and
      diffusion can be very challenging. As models of multicomponent separations rely
      on accurate depictions of protein displacement and elution, a straightforward
      method is desired to measure the mobility of bound protein in chromatographic
      media. We have adapted fluorescence recovery after photobleaching (FRAP) methods
      to study transport and exchange of protein at equilibrium in a single particle.
      Further, we have developed a mathematical model to capture diffusion and
      desorption rates governing fluorescence recovery and investigate how these rates
      vary as a function of protein size, binding strength and media type. An emphasis
      is placed on explaining differences between polymer-modified and traditional
      media, which in the former case is characterized by rapid uptake, slow
      displacement and large elution pools, differences that have been postulated to
      result from steric and kinetic limitations. Finally, good qualitative agreement
      is achieved predicting flow confocal displacement profiles in polymer-modified
      materials, based solely on estimates of kinetic and diffusion parameters from
      FRAP observations.

PMID- 24685164
TI  - Protein adsorption to poly(ethylenimine)-modified Sepharose FF: III. Comparison
      between different proteins.
AB  - Previously, we studied bovine serum albumin (BSA) uptake to poly(ethylenimine)
      (PEI)-grafted Sepharose resins, and an ionic capacity (IC) range (600-740mmol/L)
      for steep increases of both protein capacity (qm) and effective pore diffusion
      coefficient (De) was found. In this work, seven PEI-grafted Sepharose FF resins
      at IC range of 270-1030mmol/L were synthesized to investigate the effect of
      protein properties on the adsorption and uptake kinetics using BSA and gamma
      globulin as two model proteins. For BSA, the change trends of qm and De values
      with IC were well consistent with the previous results. For gamma-globulin, the
      qm values increased slowly till reaching a maximum value at IC=560mmol/L and then
      decreased rapidly at IC>560mol/L. The De values nearly kept unchanged at low ICs
      (IC<460mmol/L), and increased steeply at IC>460mmol/L till reaching a maximum at
      680mmol/L (De/D0=0.48+/-0.01). After that increase, the De values for gamma
      globulin dropped quickly at IC>680mol/L, which was not observed for BSA. It is
      interesting to note that in the narrow IC range of 460-680mmol/L, the De values
      of gamma-globulin increased dramatically for more than four folds. Moreover, it
      is notable that the IC range where the hopping of De values occurred for gamma
      globulin was earlier than that for BSA (460 vs. 560mmol/L). The earlier hopping
      of gamma-globulin uptake rate was attributed to its larger size and less net
      charge, which facilitated the happenings of the "chain delivery" effect. The
      quick drops of both qm and De values for gamma-globulin at IC>680mmol/L were
      considered due to its large size, which led to the significant decrease of its
      effective pore volume. The results indicate that both PEI layer and protein size
      played important roles in protein adsorption to PEI-grafted resins, and further
      prove the "chain delivery" effect did contributed significantly to the uptake
      rate hopping in the PEI-grafted resins. This work could also help the design and
      selection of resins based on protein characteristics and benefit optimization of
      practical chromatographic processes for therapeutic proteins with PEI-grafted
      anion exchangers. 

PMID- 24685165
TI  - Optimised concentration and purification of retroviruses using membrane
      chromatography.
AB  - The ability of an anion exchange membrane to purify a gamma-retrovirus was
      assessed and optimised with respect to different loading and wash buffers.
      Recoveries of infectious virus greater than 50% were consistently obtained, while
      specific titre was increased up to one thousand fold when compared to the
      material loaded. Specific proteins removed and retained by this optimised process
      were identified by mass spectrometry. It was possible to successfully bind and
      elute the equivalent of 1.27 * 10(8) Ifu/ml of ion exchange membrane. This could
      then be highly concentrated, with infectious virus concentrated to a maximum of
      420-fold compared to the load.

PMID- 24685166
TI  - Multimodal chromatography: Characterization of protein binding and selectivity
      enhancement through mobile phase modulators.
AB  - The unique selectivity of mixed mode chromatography resins is driving increasing
      utilization of these novel selectivities into bioprocess applications. There is a
      need for improved fundamental understanding of protein binding to these
      stationary phases to enable the development of efficient and robust purification
      processes. A panel of four monoclonal antibodies and two model proteins were
      employed to characterize protein interaction with a mixed-mode chromatographic
      resin comprising a hydrophobic ligand with cation-exchange functionality. Binding
      of these proteins was studied as a function of salt concentration and pH in the
      presence of various mobile phase modulators. This knowledge was applied towards
      screening mobile phase modulators that could selectively decrease host cell
      protein levels during monoclonal antibody purification.

PMID- 24685167
TI  - Optimization of solid phase microextraction coatings for liquid chromatography
      mass spectrometry determination of neurotransmitters.
AB  - A simple solid phase microextraction method coupled to liquid chromatography mass
      spectrometry is introduced for the analysis of neurotransmitter compounds with a
      wide range of polarities in biological matrices. A novel "reversed" reverse-phase
      chromatographic method was developed without pre-column derivatization for the
      analysis of dopamine, serotonin, gamma aminobutyric acid and glutamate. New solid
      phase microextraction "in house" coatings using mixed-mode solid phase extraction
      particles were prepared, and used for the extraction of polar neurotransmitters.
      The polymer-support base reverse phase mixed-mode sorbents with strong ion
      exchange properties generally had higher extraction efficiencies compared to
      similar sorbents with weak ion exchange properties. The linear range was
      determined to be between 0.01 and 150ng/mL for all the analytes, except for GABA,
      which was from 0.1 to 100ng/mL. The limit of detection range was from 6 to
      10pg/mL for all the neurotransmitters, and the limits of quantitation were in the
      range of 20-35pg/mL. The results demonstrate the potential of the SPME-LC-MS/MS
      technique for bioanalysis of small polar endogenous compounds, such as
      neurotransmitters, from various biological matrices using the mixed-mode sorbents
      as the extraction phase. 

PMID- 24685168
TI  - Rapid and high-throughput determination of endogenous cytokinins in Oryza sativa
      by bare Fe3O4 nanoparticles-based magnetic solid-phase extraction.
AB  - A rapid method was developed for determination of endogenous cytokinins (CKs)
      based on magnetic solid-phase extraction (MSPE) followed by ultra-performance
      liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We illustrated the
      hydrophilic character of bare Fe3O4 nanoparticles that were directly used as a
      MSPE sorbent for rapid enrichment of endogenous CKs from complex plant extract.
      To the best of our knowledge, this is the first report of bare Fe3O4 directly
      used as efficient extraction sorbent to enrich target CKs based on hydrophilic
      interaction. Under the optimized conditions, a rapid, sensitive and high
      throughput method for the determination of 16 CKs was established by combination
      of MSPE with UPLC-MS/MS. Good linearity was obtained with correlation
      coefficients (r) from 0.9902 to 0.9998. The limits of detection (LODs) and
      quantification (LOQs) ranged from 1.2 pg mL(-1) to 391.3 pg mL(-1) and 4.1 pg mL(
      1) to 1304.3 pg mL(-1), respectively. 16 CKs could be successfully determined in
      spiked sample with 80.6-117.3% recoveries and the relative standard deviations
      (RSDs) were less than 16.6%. Finally, 10 endogenous CKs were successfully
      quantified in 50mg Oryza sativa sample using the developed MSPE-UPLC-MS/MS
      method.

PMID- 24685169
TI  - How might global health master deadly sins and strive for greater virtues?
AB  - In the spirit of critical reflection, we examine how the field of global health
      might surmount current challenges and prioritize its ethical mandate, namely to
      achieve, for all people, equity in health. We use the parlance of mastering
      deadly sins and striving for greater virtues in an effort to review what is
      needed to transform global health action. Global health falls prey to four main
      temptations: coveting silo gains, lusting for technological solutions, leaving
      broad promises largely unfulfilled, and boasting of narrow successes. This
      necessitates a change of heart: to keep faith with the promise it made, global
      health requires a realignment of core values and a sharper focus on the primacy
      of relationships with the communities it serves. Based on the literature to date,
      we highlight six steps to re-orienting global health action. Articulating a
      coherent global health agenda will come from principled action, enacted through
      courage and prudence in decision-making to foster people-centered systems of care
      over the entire lifespan. 

PMID- 24685170
TI  - Step-by-step guideline for disease-specific costing studies in low- and middle
      income countries: a mixed methodology.
AB  - BACKGROUND: Disease-specific costing studies can be used as input into cost
      effectiveness analyses and provide important information for efficient resource
      allocation. However, limited data availability and limited expertise constrain
      such studies in low- and middle-income countries (LMICs). OBJECTIVE: To describe
      a step-by-step guideline for conducting disease-specific costing studies in LMICs
      where data availability is limited and to illustrate how the guideline was
      applied in a costing study of cardiovascular disease prevention care in rural
      Nigeria. DESIGN: The step-by-step guideline provides practical recommendations on
      methods and data requirements for six sequential steps: 1) definition of the
      study perspective, 2) characterization of the unit of analysis, 3) identification
      of cost items, 4) measurement of cost items, 5) valuation of cost items, and 6)
      uncertainty analyses.Please provide the significance of asterisk given in table
      body. RESULTS: We discuss the necessary tradeoffs between the accuracy of
      estimates and data availability constraints at each step and illustrate how a
      mixed methodology of accurate bottom-up micro-costing and more feasible
      approaches can be used to make optimal use of all available data. An illustrative
      example from Nigeria is provided. CONCLUSIONS: An innovative, user-friendly
      guideline for disease-specific costing in LMICs is presented, using a mixed
      methodology to account for limited data availability. The illustrative example
      showed that the step-by-step guideline can be used by healthcare professionals in
      LMICs to conduct feasible and accurate disease-specific cost analyses.

PMID- 24685171
TI  - Health literacy: a critical concept for public health.

PMID- 24685172
TI  - Alternative translation initiation in immunity: MAVS learns new tricks.
AB  - Translational control of gene expression contributes to various aspects of immune
      function [1]. Recent results by Brubaker et al. [2] show how alternative
      translation initiation produces distinct isoforms of Mitochondrial Antiviral
      Signaling (MAVS), an adaptor protein associated with RIG-I and MDA5 that possess
      unique immunomodulatory properties. 

PMID- 24685173
TI  - Cognitive functioning and late-life depression.
AB  - This brief report provides an introduction to the topic of cognitive functioning
      in late-life depression (LLD). In addition to providing a review of the
      literature, we present a framework for understanding the heterogeneity of
      cognitive outcomes in this highly prevalent disorder. In addition, we discuss the
      relationship between LLD and dementia, and highlight the importance of regularly
      assessing cognitive functioning in older adults who present with depressive
      symptoms. If cognitive deficits are discovered during a neuropsychological
      assessment, we recommend referral to a geriatric psychiatrist or cognitive
      neurologist, for evaluation and treatment of the patient's symptoms.

PMID- 24685174
TI  - Glued versus stapled anastomosis of the colon: an experimental study to determine
      comparative resistance to intraluminal pressure.
AB  - BACKGROUND: This study compared the resistance of glued versus stapled
      anastomosis of the colon to intraluminal pressures at different times during
      healing. METHODS: Forty seven female domestic pigs, mean weight of 30.7 kg, were
      used. Maximum physiological luminal pressures, i.e. the pressure resisted by a
      catheter inserted into the intestinal lumen via a puncture without it being
      released and without injury to the surrounding intestinal wall, was performed in
      5 control animals. The remaining 42 animals were divided into 3 groups of 14
      animals each based on time from anastomosis construction. Each group was divided
      into 2 subgroups with stapled or glued anastomoses. Intraluminal pressure was
      measured on the first, third, and fifth day post-surgery. RESULTS: The maximum
      pressures resisted by anastomoses were significantly higher than the
      physiological pressures in all groups. At all time points, stapled anastomoses
      resisted higher intraluminal pressures than glued ones. However, glued
      anastomoses resisted pressures significantly higher than physiological pressure.
      As healing advanced, glued anastomoses neared the resistance to intraluminal
      pressures of stapled anastomoses. CONCLUSION: Healing with absorbable synthetic
      glue was as good as with staples. Glued anastomoses resisted pressures that were
      statistically significantly higher than physiological intraluminal colon
      pressures but lower than stapled ones.

PMID- 24685175
TI  - NMDAR-regulated dynamics of layer 4 neuronal dendrites during thalamocortical
      reorganization in neonates.
AB  - Thalamocortical (TC) connectivity is reorganized by thalamic inputs during
      postnatal development; however, the dynamic characteristics of TC reorganization
      and the underlying mechanisms remain unexplored. We addressed this question using
      dendritic refinement of layer 4 (L4) stellate neurons in mouse barrel cortex
      (barrel cells) as a model; dendritic refinement of L4 neurons is a critical
      component of TC reorganization through which postsynaptic L4 neurons acquire
      their dendritic orientation toward presynaptic TC axon termini. Simultaneous
      labeling of TC axons and individual barrel cell dendrites allowed in vivo time
      lapse imaging of dendritic refinement in the neonatal cortex. The barrel cells
      reinforced the dendritic orientation toward TC axons by dynamically moving their
      branches. In N-methyl-D-aspartate receptor (NMDAR)-deficient barrel cells, this
      dendritic motility was enhanced, and the orientation bias was not reinforced. Our
      data suggest that L4 neurons have "fluctuating" dendrites during TC
      reorganization and that NMDARs cell autonomously regulate these dynamics to
      establish fine-tuned circuits. 

PMID- 24685176
TI  - Soluble Abeta oligomers are rapidly sequestered from brain ISF in vivo and bind
      GM1 ganglioside on cellular membranes.
AB  - Soluble Abeta oligomers contribute importantly to synaptotoxicity in Alzheimer's
      disease, but their dynamics in vivo remain unclear. Here, we found that soluble
      Abeta oligomers were sequestered from brain interstitial fluid onto brain
      membranes much more rapidly than nontoxic monomers and were recovered in part as
      bound to GM1 ganglioside on membranes. Abeta oligomers bound strongly to GM1
      ganglioside, and blocking the sialic acid residue on GM1 decreased oligomer
      mediated LTP impairment in mouse hippocampal slices. In a hAPP transgenic mouse
      model, substantial levels of GM1-bound Abeta42 were recovered from brain membrane
      fractions. We also detected GM1-bound Abeta in human CSF, and its levels
      correlated with Abeta42, suggesting its potential as a biomarker of Abeta-related
      membrane dysfunction. Together, these findings highlight a mechanism whereby
      hydrophobic Abeta oligomers become sequestered onto GM1 ganglioside and
      presumably other lipids on neuronal membranes, where they may induce progressive
      functional and structural changes.

PMID- 24685178
TI  - Chipping fracture resistance of dental CAD/CAM restorative materials: part I-
      procedures and results.
AB  - OBJECTIVE: The edge chipping test was used to measure the fracture resistance of
      CAD/CAM dental restoration ceramics and resin composites. METHODS: An edge
      chipping machine was used to evaluate six materials including one feldspathic
      porcelain, two glass ceramics, a filled resin-composite, a yttria-stabilized
      zirconia, and a new ceramic-resin composite material. Force versus edge distance
      data were collected over a broad range of forces and distances. Data were
      analyzed by several approaches and several chipping resistance parameters were
      evaluated. The effects of using different indenter types were explored. RESULTS:
      The force versus distance trends were usually nonlinear with good fits to a power
      law equation with exponents usually ranging from 1.2 to 1.9. The order of
      chipping resistance (from least to greatest) was: feldspathic porcelain and a
      leucite glass ceramic (which were similar), followed by the lithium disilicate
      glass ceramic and the two resin composites (which were similar), and finally the
      zirconia which had the greatest resistance to chipping. Chipping with a Vickers
      indenter required 28-45% more force than with the sharp conical 120 degrees 
      indenter. The two indenters rank materials approximately the same way. The power
      law exponents were very similar for the two indenters for a particular material,
      but the exponents varied with material. The Rockwell C indenter gives different
      power law trends and rankings. SIGNIFICANCE: Despite the variations in the trends
      and indenters, simple comparisons between materials can be made by chipping with
      sharp conical 120 degrees  or Vickers indenters at 0.50mm. Broad distance ranges
      are recommended for trend evaluation.

PMID- 24685177
TI  - The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and
      engrailed.
AB  - Specific vulnerability and degeneration of the dopaminergic neurons in the
      substantia nigra pars compacta of the midbrain is the pathological hallmark of
      Parkinson's disease. A number of transcription factors regulate the birth and
      development of this set of neurons and some remain constitutively expressed
      throughout life. These maintenance transcription factors are closely associated
      with essential neurophysiological functions and are required ultimately for the
      long-term survival of the midbrain dopaminergic neurons. The current review
      describes the role of two such factors, Nurr1 and engrailed, in differentiation,
      maturation, and in normal physiological functions including acquisition of
      neurotransmitter identity. The review will also elucidate the relationship of
      these factors with life, vulnerability, degeneration and death of mesencephalic
      dopaminergic neurons in the context of Parkinson's disease. 

PMID- 24685179
TI  - Chipping fracture resistance of dental CAD/CAM restorative materials: part 2.
      Phenomenological model and the effect of indenter type.
AB  - The edge chipping resistances of six CAD/CAM dental restoration materials are
      analyzed and correlated to other mechanical properties. A new quadratic
      relationship that is based on a phenomenological model is presented. OBJECTIVE:
      The purpose of this study was to further analyze the edge chipping resistance of
      the brittle materials evaluated in Part 1. One objective was to determine why
      some force-distance trends were linear and others were nonlinear. A second
      objective was to account for differences in chipping resistance with indenter
      type. METHODS: Edge chipping experiments were conducted with different indenters,
      including some custom-made sharp conical indenters. A new force - distance
      quadratic expression was correlated to the data and compared to the linear and
      power law trends. RESULTS: The new quadratic function was an excellent fit in
      every instance. It can account for why some materials can be fit by a linear
      trend, while others can be fit by the power law trend. The effects of indenter
      type are accounted for variations in crack initiation and by the wedging stresses
      once an indentation hole is created. SIGNIFICANCE: The new quadratic force - edge
      distance function can be used with edge chipping data for all brittle materials,
      not just those evaluated in this study. The data trends vary from linear to
      nonlinear depending upon the material's hardness, fracture toughness, and elastic
      modulus.

PMID- 24685180
TI  - Computed tomography follow-up of acute portal vein thrombosis.
AB  - PURPOSE: To assess the evolution of acute portal vein thrombosis by computed
      tomography (CT). PATIENTS AND METHODS: Retrospective single-centre study (2005
      2011) including 23 patients who had an initial CT scan and a CT scan during the
      first year. The analysis compared the last CT scan available with that of the
      initial CT scan. Neoplastic thrombosis, extrinsic compressions and cavernomas
      were excluded. All patients received anticoagulant treatment. RESULTS: The causes
      included: cirrhoses (n = 6), blood disorders (n = 4), locoregional inflammations
      and infections (n = 8), abdominal surgery (n = 1). The thrombosis was idiopathic
      in 4 cases. After a mean follow-up of 7.7 months, 7 patients (30%) benefited from
      a restitutio ad integrum of the portal system, a stable or partially regressive
      thrombosis was noted in 12 patients (52%) and an aggravation of the thrombosis
      was noted in 4 patients (18%). In the sub-group of portal vein thrombosis,
      repermeabilisation was noted in 37.5% of the patients (6/16) and 6 cavernomas
      developed. CONCLUSION: CT monitoring helps follow the evolution of an acute
      portal vein thrombosis and demonstrates complete repermeabilisation of the portal
      vein in 30% of the patients.

PMID- 24685181
TI  - Heavy ion radiography and tomography.
AB  - In the latest years, radiation therapy with ion beams has been rapidly spreading
      worldwide. This is mainly due to the favourable interaction properties of ion
      beams with matter, offering the possibility of more conformal dose deposition
      with superior sparing of healthy tissue in comparison to conventional photon
      radiation. Moreover, heavier ions like carbon offer a selective increase of
      biological effectiveness which can be advantageous for the treatment of tumours
      being resistant to sparsely ionizing radiation. However, full clinical
      exploitation of the advantages offered by ion beams is still challenged by the
      lack of exact knowledge of the beam range within the patient. Therefore,
      increasing research efforts are being devoted to the goal of reducing range
      uncertainties in ion beam therapy. In this context, ion transmission imaging is
      being recognized as a promising modality capable of providing valuable pre- (or
      even "in-between") treatment information on the patient-specific stopping
      properties for indirect in-vivo range verification and low dose image guidance at
      the treatment site. The more recent availability of energetic ion beam sources at
      therapeutic treatment facilities, in combination with the advances in detector
      technologies and computational power, have considerably renewed the interest in
      this imaging technique. Nowadays, many research efforts are being devoted to the
      development of novel detector prototypes for heavy ion radiography and
      tomography, as will be reviewed in this contribution. 

PMID- 24685182
TI  - Accuracy of 2-hydroxyglutarate quantification by short-echo proton-MRS at 3 T: a
      phantom study.
AB  - PURPOSE: We set out to investigate the potential confounding effect of variable
      concentration of N-acetyl-l-aspartate (NAA) and Glutamate (Glu) on measurement of
      the brain oncometabolite 2-hydroxyglutarate (2HG) using a standard MRS protocol.
      This issue may arise due to spectral overlap at clinical magnetic field strengths
      and thus complicate the usage of 2HG as a putative biomarker of gliomas bearing
      mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes. METHODS: Spectra
      from 25 phantoms (50 mL falcon test tubes) containing a range of known
      concentrations of 2HG, NAA and Glu were acquired using a clinical 3 T scanner
      with a quadrature head coil, single-voxel point-resolved spectroscopy sequence
      with TE = 30 ms. Metabolite concentrations were estimated by linear combination
      analysis and a simulated basis set. RESULTS: NAA and Glu concentrations can have
      a significant confounding effect on 2HG measurements, whereby the negative
      changes in concentration of these metabolites typically observed in
      (peri)lesional areas can lead to under-estimation of 2HG concentration with
      respect to spectra acquired in presence of physiological levels of NAA and Glu.
      CONCLUSION: The confounding effect of NAA and Glu concentration changes needs to
      be considered: in patients, it may mask the presence of 2HG at low
      concentrations, however it is not expected to lead to false positives. 2HG data
      acquired using standard short echo-time MRS protocols should be considered with
      caution.

PMID- 24685183
TI  - Real-time PCR detection of the HhaI tandem DNA repeat in pre- and post-patent
      Brugia malayi Infections: a study in Indonesian transmigrants.
AB  - BACKGROUND: Lymphatic filariasis caused by Wuchereria bancrofti or Brugia spp. is
      a public health problem in developing countries. To monitor bancroftian
      filariasis infections, Circulating Filarial Antigen (CFA) test is commonly used,
      but for brugian infections only microfilariae (Mf) microscopy and indirect IgG4
      antibody analyses are available. Improved diagnostics for detecting latent
      infections are required. METHODS: An optimized real-time PCR targeting the
      brugian HhaI repeat was validated with plasma from microfilariae negative
      Mongolian gerbils (jirds) infected with B. malayi. Plasma samples from
      microfilaremic patients infected with B. malayi or W. bancrofti were used as
      positive and negative controls, respectively. PCR results of plasma samples from
      a transmigrant population in a B. malayi endemic area were compared to those of
      life-long residents in the same endemic area; and to IgG4 serology results from
      the same population. To discriminate between active infections and larval
      exposure a threshold was determined by correlation and Receiver-Operating
      Characteristics (ROC) curve analyses. RESULTS: The PCR detected HhaI in pre
      patent (56 dpi) B. malayi infected jirds and B. malayi Mf-positive patients from
      Central Sulawesi, Indonesia. HhaI was also detected in 9/9 elephantiasis
      patients. In South Sulawesi 87.4% of the transmigrants and life-long residents
      (94% Mf-negative) were HhaI PCR positive. Based on ROC-curve analysis a threshold
      for active infections was set to >53 HhaI copies/MUl (AUC: 0.854). CONCLUSIONS:
      The results demonstrate that the HhaI PCR detects brugian infections with greater
      sensitivity than the IgG4 test, most notably in Mf-negative patients (i.e. pre
      patent or latent infections).

PMID- 24685184
TI  - Overnight orthokeratology is comparable with atropine in controlling myopia.
AB  - BACKGROUND: Many efforts have been invested in slowing progression of myopia.
      Among the methods, atropine administration and orthokeratology (OK) are most
      widely used. This study analyzed the efficacy of atropine and OK lens in
      controlling myopia progression and elongation of axial length. METHODS: This
      retrospective study included 105 patients (210 eyes) who wore OK lenses and 105
      patients (210 eyes) who applied 0.125% atropine every night during the 3
      following period. Student t-test, linear regression analysis, repeated measure
      ANOVA, and Pearson's correlation coefficient were used for statistical analysis.
      RESULTS: The change in axial length per year was 0.28 +/- 0.08 mm, 0.30 +/- 0.09
      mm, and 0.27 +/- 0.10 mm in the OK lens group, and 0.38 +/- 0.09 mm, 0.37 +/-
      0.12 mm, and 0.36 +/- 0.08 mm in the atropine group for years 1, 2, and 3,
      respectively. Linear regression analysis revealed an increase in myopia of 0.28 D
      and 0.34 D per year, and an increase in axial length of 0.28 mm and 0.37 mm per
      year in the OK lens and atropine groups, respectively. Repeated measure ANOVA
      showed significant differences in myopia (p = 0.001) and axial length (p < 0.001)
      between the atropine and OK lens groups; in astigmatism, there was no significant
      difference in these parameters (p = 0.320). Comparison of increases in axial
      length in relation to baseline myopia showed significant correlations both in the
      OK lens group (Pearson's correlation coefficient, r = 0.259; p < 0.001) and
      atropine group (r = 0.169; p = 0.014). High myopia patients benefited more from
      both OK lenses and atropine than did low myopia patients. The correlation of
      baseline myopia and myopia progression was stronger in the OK lens group then in
      the atropine group. CONCLUSIONS: OK lens is a useful method for controlling
      myopia progression even in high myopia patients.

PMID- 24685186
TI  - Optical properties of Ag nanoparticle-polymer composite film based on two
      dimensional Au nanoparticle array film.
AB  - The nanocomposite polyvinyl pyrrolidone (PVP) films containing Ag nanoparticles
      and Rhodamine 6G are prepared on the two-dimensional distinctive continuous
      ultrathin gold nanofilms. We investigate the optical properties and the
      fluorescence properties of silver nanoparticles-PVP polymer composite films
      influenced by Ag nanoparticles and Au nanoparticles. Absorption spectral analysis
      suggests that the prominently light absorption in Ag nanowire/PVP and Ag
      nanowire/PVP/Au film arises from the localized surface plasmon resonance of Ag
      nanowire and Au nanofilm. The enhanced fluorescence is observed in the presence
      of Ag nanowire and Au nanofilm, which is attributed to the excitation of surface
      plasmon polariton resonance of Ag nanowire and Au nanofilm. The gold nanofilm is
      proven to be very effective fluorescence resonance energy transfer donors. The
      fabricated novel structure, gold ultrathin continuous nanofilm, possesses high
      surface plasmon resonance properties and prominent fluorescence enhancement
      effect. Therefore, the ultrathin continuous gold nanofilm is an active substrate
      on nanoparticle-enhanced fluorescence. 

PMID- 24685185
TI  - A reduced genome decreases the host carrying capacity for foreign DNA.
AB  - BACKGROUND: Host-plasmid interactions have been discussed largely in terms of the
      influences of plasmids, whereas the contributions of variations in host genomes
      to host interactions with foreign DNA remain unclear. A strain with a so-called
      "clean genome" (i.e., MDS42) of reduced genome size has recently been generated
      from the wild-type strain MG1655, a commonly used host strain. A quantitative
      evaluation of the influence of plasmid burdens in these two Escherichia coli
      strains can not only provide an understanding of how a reduced genome responds to
      foreign DNA but also offer insights into the proper application of these strains.
      RESULTS: The decreases in growth caused by the cost of carrying foreign DNA were
      similar for the wild-type and clean-genome strains. A negative correlation
      between the growth rate and the total amount of exogenous DNA was observed in
      both strains, but a better theoretical fit with a higher statistical significance
      was found for the strain with the clean genome. Compared to the wild-type strain,
      the clean-genome strain exhibited a reduced carrying capacity for exogenous DNA,
      which was largely attributed to its ability to restrict the replication of
      foreign DNA. A tendency to allocate energy and resources toward gene expression,
      but not DNA replication, was observed in the strain with the clean genome.
      CONCLUSIONS: The possession of a clean genome constrained the plasmid copy number
      to a wild-type-equivalent load. The results indicate that the wild-type strain
      possesses a greater tolerance for foreign DNA, as in endosymbiosis, and that the
      use of strains with clean genomes will be favorable in the applications that
      require precise control and theoretical prediction.

PMID- 24685187
TI  - Biodynamics of hallux abductovalgus etiology and preoperative evaluation.
AB  - Hallux abductovalgus (HAV) is a common but complex deformity. HAV is a
      combination of deformities and abnormalities. Because HAV is not from a single
      cause or pathologic process, controversies in description and potential
      treatments exist. Although many HAV deformities appear similar, no two are the
      same and thus cannot be treated the same surgically. 

PMID- 24685188
TI  - Proximal phalangeal osteotomies for hallux abductovalgus deformity.
AB  - The primary indication for an osteotomy of the hallux proximal phalanx to correct
      hallux abductovalgus (HAV) deformities is increased hallux interphalangeus. The
      typical osteotomy is the Akin osteotomy or a variation. The Akin is a medial
      closing wedge osteotomy in the proximal phalanx. An Akin-type osteotomy is
      usually used as an adjunctive procedure for HAV to correct deformity within the
      great toe. When first metatarsal procedures and soft tissue balancing are not
      sufficient for realigning the first metatarsophalangeal joint, an Akin can be
      useful. A hallux proximal phalanx osteotomy is not indicated as the primary
      correction for HAV deformities. 

PMID- 24685189
TI  - First metatarsal head osteotomies for the correction of hallux abducto valgus.
AB  - An array of distal first metatarsal osteotomies has been described over the
      decades for the correction of hallux valgus. No one procedure is proficient in
      correcting all forms and severities of hallux valgus deformities. To optimize
      results, it is imperative for the surgeon to match a procedure and its
      modifications to the patient's deformity. The dorsal long arm chevron osteotomy
      stands at the forefront for correction of mild to moderate hallux abductovalgus.
      The results with this specific osteotomy are predictable; it allows for early
      ambulation, and it is easily modified to compensate for the deformity at hand. 

PMID- 24685190
TI  - Scarf osteotomy for correction of hallux abducto valgus deformity.
AB  - The scarf osteotomy has been used and researched extensively for many years for
      the correction of hallux valgus deformity in both the adolescent and adult
      populations. It is an inherently stable construct, which allows for early weight
      bearing and early return to activities of daily living. The scarf procedure has a
      wide array of surgical indications with great reproducibility and a low
      complication rate, and it can be performed bilaterally simultaneously, with long
      term predictability. Once the scarf procedure is mastered, it is a rewarding and
      predictable operation for both the surgeon and patient. 

PMID- 24685191
TI  - First metatarsal base osteotomies for hallux abducto valgus deformities.
AB  - Proximal first metatarsal osteotomies have historically been associated with and
      limited to treatment of severe hallux valgus deformities. These procedures are
      powerful in deformity correction and overall realignment of first ray function
      because of their ability to correct closer to the deformity's origin. When
      considering all factors in bunion correction, they are good options for
      correction of a wide range of hallux abducto valgus deformities. This article
      discusses the use of proximal metatarsal osteotomies for correction of hallux
      valgus deformity, techniques to facilitate optimal outcome, and common
      complications of these osteotomies. 

PMID- 24685193
TI  - First metatarsophalangeal joint arthrodesis in the treatment of hallux valgus.
AB  - First metatarsophalangeal joint arthrodesis is a reliable procedure with
      predictable outcomes in the treatment of moderate-to-severe hallux valgus with
      degenerative changes of the joint. It offers better functional outcome compared
      to arthroplasty with or without prosthesis in appropriate patient populations.
      Recent studies have shown that with appropriate fixation, early weight bearing
      may be initiated without an increase in nonunion. 

PMID- 24685192
TI  - Fixation updates for hallux valgus correction.
AB  - Fixation options for hallux valgus correction vary. Although some methods are
      newer and more advanced, even the older techniques are successful in appropriate
      situations. Kirschner wires and cerclage wiring have their place in proximal
      phalanx and first metatarsal osteotomies. They are useful for fusion procedures,
      depending on patient bone quality. Advancements with staple fixation allow the
      surgeon to apply compression with this device. One of the most stable forms of
      fixation is the bone screw. By providing a stable construct with good
      interfragmentary compression, primary bone healing is facilitated. The more
      recent use of rigid locking plates has allowed for earlier weight bearing
      following fusion procedures. 

PMID- 24685194
TI  - Revision hallux valgus: causes and correction options.
AB  - The need for revision hallux valgus surgery is a problem all surgeons encounter.
      Revision of a failed hallux valgus surgery is often difficult, and very little
      research exists and few papers have been presented on the topic. Hallux valgus
      failure has multiple causes, including reoccurrence, avascular necrosis,
      malunion, nonunion, and hallux varus. These problems can be difficult to address,
      although some are far more difficult to correct than others. This article details
      the underlying causes of hallux valgus failure, the workup, and the revision
      options, with the hope of providing greater education and research on this
      difficult problem. 

PMID- 24685195
TI  - Contemporary approaches and advancements to the Lapidus procedure.
AB  - The Lapidus procedure as evolved over the last 50 years. What originally was a
      difficult procedure with poor outcomes has changed to a procedure that allows for
      ideal realignment of the deformity at its source, improved foot alignment, and
      minimal to no need for further surgery. The authors now use a weight bearing
      plate which has improved overall patient care, with a minimized risk of
      nonunions, and more rapid return to early weight bearing and range of motion.
      This method has opened up the procedure to more patients, decreased the recovery
      time, and allowed for early physical therapy, resulting in outstanding patient
      outcomes. 

PMID- 24685196
TI  - Physical therapy post-hallux abducto valgus correction.
AB  - This article discusses physical therapy considerations after hallux valgus
      correction. Hallux valgus is a fairly common occurrence, and corrective surgery
      is an option when conservative measures fail. Symptoms such as pain, swelling,
      and difficulty walking may persist after surgical correction of bunion deformity
      that addresses soft tissue and bone structure. Physical therapy is helpful after
      corrective hallux valgus surgery to address impairments and continued dysfunction
      and to improve overall patient outcome expectations. This article describes the
      benefits of a multifaceted physical therapy program after hallux valgus
      correction. 

PMID- 24685197
TI  - Hallux abducto valgus surgery.

PMID- 24685198
TI  - Hallux valgus and bunion surgery.

PMID- 24685199
TI  - The acceptability of care delegation in skill-mix: the salience of trust.
AB  - The aim of this research was to explore the acceptability of care delegation in
      skill-mix, using the views and experiences of patients and parents of children
      treated by dental therapists as a case study. A purposive sample of 15 adults
      whose care, or that of their children, had been delegated to dental therapists in
      English dental practices was interviewed using narrative and ethnographic
      techniques (July 2011 - May 2012). Experiences were overwhelmingly positive with
      the need for trust in clinicians and the health system emerging as a key factor
      in its acceptability. Perceptions of general and dental health services ranged
      from them being a collectivist public service to a more consumerist marketised
      service, with the former seemingly associated with notions of dentistry as a
      trusted system working for the social good. Interpersonal trust appeared built,
      sustained (and undermined) by the affective behaviour, perceived competence, and
      continuity of care with clinicians providing care, and contributed to trust in
      the system. It also appeared to compensate for gaps in knowledge needed for
      patient decision-making. Overall, where trust existed, delegation of care was
      acceptable. An increasingly marketised health system, and emphasis on the patient
      as a consumer, may challenge trust and acceptability of delegation, and undermine
      the notion of patient-centred health care. 

PMID- 24685200
TI  - Future biologic therapies in asthma.
AB  - Despite the administration of appropriate treatment, a high number of patients
      with asthma remain uncontrolled. This suggests the need for alternative
      treatments that are effective, safe and selective for the established asthma
      phenotypes, especially in patients with uncontrolled severe asthma. The most
      promising options among the new asthma treatments in development are biological
      therapies, particularly those monoclonal antibodies directed at selective
      targets. It should be noted that the different drugs, and especially the new
      biologics, act on very specific pathogenic pathways. Therefore, determination of
      the individual profile of predominant pathophysiological alterations of each
      patient will be increasingly important for prescribing the most appropriate
      treatment in each case. The treatment of severe allergic asthma with anti-IgE
      monoclonal antibody (omalizumab) has been shown to be effective in a large number
      of patients, and new anti-IgE antibodies with improved pharmacodynamic properties
      are being investigated. Among developing therapies, biologics designed to block
      certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13
      (lebrikizumab), have a greater chance of being used in the clinic. Perhaps
      blocking more than one cytokine pathway (such as IL-4 and IL-13 with dulipumab)
      might confer increased efficacy of treatment, along with acceptable safety.
      Stratification of asthma based on the predominant pathogenic mechanisms of each
      patient (phenoendotypes) is slowly, but probably irreversibly, emerging as a
      tailored medical approach to asthma, and is becoming a key factor in the
      development of drugs for this complex respiratory syndrome. 

PMID- 24685201
TI  - Diagnosis and treatment of neuroendocrine lung tumors.
AB  - Pulmonary neuroendocrine tumors (PNT) encompass a broad spectrum of tumors
      including typical carcinoid (TC) and atypical (AC) tumors, large-cell
      neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). Although no
      variety can be considered benign, AC and TC have a much lower metastatic
      potential, are usually diagnosed in early stages, and most are candidates for
      surgical treatment. Several chemotherapy (CT) regimens are available in the case
      of recurrence or in advanced stages, although scientific evidence is
      insufficient. LCNEC, which is currently classified alongside large-cell
      carcinomas, have molecular features, biological behavior and CT sensitivity
      profile closely resembling SCLC. Pathological diagnosis is often difficult,
      despite the availability of immunohistochemical techniques, and surgical
      specimens may be necessary. The diagnostic tests used are similar to those used
      in other lung tumors, with some differences in the optimal tracer in positron
      emission tomography. The new TNM classification is useful for staging these
      tumors. Carcinoid syndrome, very rare in PNT, may cause symptoms that are
      difficult to control and requires special therapy with somatostatin analogs and
      other drugs. Overall, with the exception of SCLC, new trials are needed to
      provide a response to the many questions arising with regard to the best
      treatment in each lineage and each stage. 

PMID- 24685203
TI  - Is low health literacy associated with overweight and obesity in adolescents: an
      epidemiology study in a 12-16 years old population, Nanning, China, 2012.
AB  - BACKGROUND: The problem of overweight and obesity in children and adolescents is
      considered an epidemic in both developed and developing world by the WHO. There
      has been little study on the relationship between health literacy and body weight
      among adolescents.This epidemiological study aims to investigate the association
      between low health literacy and overweight and obesity among a population of
      Chinese adolescents aged 12-16 years in the city of Nanning, China in 2012.
      METHODS: This study was a population-based cross-sectional health survey
      utilising a two-stage random cluster sampling design. The sample consisted of
      high school students aged between 12-16 years with the total student population
      attending high schools in a large city as the sample frame. Health literacy was
      measured by the Chinese version of the short form of the Test of Functional
      Health Literacy translated for and validated among Taiwanese adolescents.
      Overweight and obesity were assessed in accordance to the recommendation of the
      World Health Organization (WHO) Global Database of Body Mass Index classification
      methods. Data were analysed using logistic regression modelling techniques with
      adjustment to the cluster sampling effect. RESULTS: A total of 1035 students
      responded to the survey providing usable information with 628 (48.1%) respondents
      classified as high, 558 (42.8%) moderate, and 119 (9.1%) low levels of health
      literacy. After adjusting for potential confounding factors and the cluster
      sampling effect, low health literacy was significantly associated with overweight
      and obesity (OR = 1.84, 95% C.I. = 1.13-2.99). CONCLUSION: Results suggested that
      low health literacy level was associated with many aspects of adolescence health
      including their body weight. These results have public health implications on an
      important global problem of adolescence body weight. Enhancing the health
      literacy should be considered as part of the strategies in combating adolescence
      weight problem.

PMID- 24685202
TI  - Nematode phospholipid metabolism: an example of closing the genome-structure
      function circle.
AB  - Parasitic nematodes that infect humans, animals, and plants cause health
      problems, livestock and agricultural losses, and economic damage worldwide and
      are important targets for drug development. The growing availability of nematode
      genomes supports the discovery of new pathways that differ from host organisms
      and are a starting point for structural and functional studies of novel
      antiparasitic targets. As an example of how genome data, structural biology, and
      biochemistry integrate into a research cycle targeting parasites, we summarize
      the discovery of the phosphobase methylation pathway for phospholipid synthesis
      in nematodes and compare the phosphoethanolamine methyltransferases (PMTs) from
      nematodes, plants, and Plasmodium. Crystallographic and biochemical studies of
      the PMTs in this pathway provide a foundation that guides the next steps that
      close the genome-structure-function circle. 

PMID- 24685204
TI  - [More controversies about direct-to-consumer genetic profiles].

PMID- 24685205
TI  - [Synthesis of MHC class I antigenic peptides in the nucleus: a role for the
      nuclear translation at last?].

PMID- 24685207
TI  - [Human MX2 is an effector of IFN-mediated resistance to HIV-1 infection].

PMID- 24685206
TI  - [IAP and Rho finally connected].

PMID- 24685208
TI  - [Shear stress triggers membrane insertion of voltage-gated potassium channels in
      atrial myocytes].

PMID- 24685209
TI  - [Immunologic mechanisms involved in rituximab failure during adult immune
      thrombocytopenia].

PMID- 24685210
TI  - [Aspartate: an essential amino acid for the physiology and virulence of the
      tuberculosis bacillus].

PMID- 24685211
TI  - [Cholesterol, neuronal activity and Alzheimer disease].

PMID- 24685212
TI  - [Can the phenomenology of near death experiences memories be compared to memories
      of real and imagined events?].

PMID- 24685213
TI  - [A novel inhibitor of the Arp2/3 complex, Arpin, controls cell migration].

PMID- 24685214
TI  - [Human skin carcinoma arising from kidney transplant-derived epithelial cells].

PMID- 24685215
TI  - [Innate lymphoid cells control the intestinal commensal bacteria adaptive
      response].

PMID- 24685216
TI  - [Gut microbiota and digestion of polysaccharides].
AB  - The distal gut microbiota corresponds to all the microorganisms, essentially
      bacteria, that reside commonly in the colon. The microbial population is
      characterized by a large taxonomical diversity, counting approximately a thousand
      distinct bacterial species for a single individual. The pace of investigations of
      this microbial system has greatly accelerated these last few years, fuelled by
      the advent of metagenomics techniques, which do not rely on bacterial
      cultivation, but utilize high throughput DNA sequencing. In just a few years
      studies of the intestinal microbiota have become fashionable, albeit with often
      contradictory results when attempting to correlate changes in microbial
      composition to diverse pathologies. The article focuses on one of the essential
      functions of the distal gut microbiota: the digestion of the immense variety of
      polysaccharides from our diet that enzymes of the host cannot breakdown.

PMID- 24685217
TI  - [Chromothripsis, an unexpected novel form of complexity for chromosomal
      rearrangements].
AB  - The recent discovery of a new kind of massive chromosomal rearrangement in
      different cancers, named "chromothripsis" (chromo for chromosome, thripsis for
      shattering) has questioned the established models for a progressive development
      of tumors. Indeed, this phenomenon, which is characterized by the shattering of
      one (or a few) chromosome segments followed by a random reassembly of the
      fragments generated, occurs during one unique cellular event. The same phenomenon
      was identified in constitutional genetics in patients with various developmental
      pathologies, indicating that chromothripsis also occurs at the germ cell level.
      Diverse situations can cause chromothripsis (radiations, telomere erosion,
      abortive apoptosis, etc.), and two express "repair routes" are used by the cell
      to chaotically reorganise the chromosomal regions concerned: non-homologous end
      joining and repair by replicative stress. The in-depth analysis of the DNA
      sequences involved in the regions of chromothripsis leads to a better
      understanding of the molecular basis of chromothripsis and also helps to better
      apprehend its unexpected role in the development of constitutional pathologies
      and the progression of cancers.

PMID- 24685218
TI  - [Prokineticins: new regulatory peptides in human reproduction].
AB  - During the last decade, there has been growing evidence for the involvement of
      prokineticins and their receptors (PROK/PROKR) in human reproduction, with
      multiple roles in the female and male reproductive systems. The PROK/PROKR
      signalling complex has been reported as a new actor in ovary, uterus, placenta,
      and testis physiology, with marked dysfunction in various pathological conditions
      such as polycystic ovary syndrome, recurrent pregnancy loss, preeclampsia, and
      ectopic pregnancy. Altogether, the results strongly suggest the involvement of
      prokineticins in spermatogenesis, oocyte competence, embryo implantation,
      pregnancy, and delivery, and argue for the clinical relevance of these cytokines
      and their receptors as diagnostic markers for several reproductive diseases. 

PMID- 24685219
TI  - [Innate lymphoid cells: new players of the mucosal immune response].
AB  - ILC have recently emerged as new subsets of innate lymphoid effectors devoid of
      antigen receptors and harboring strikingly diverse functions. Three main sub
      types of ILC can be distinguished based on their developmental requirements and
      functions. ILC1 include cytotoxic natural killer cells and T-bet dependent
      IFNgamma producing cells. ILC2 are generated from bone marrow progenitors
      expressing GATA-3 and produce type 2 cytokines such as IL-5 and IL-13 in response
      to infections by parasitic worms and Influenza virus. Type 3 ILC are dependent on
      RORgammat, they are involved in the maintenance of the gut homeostasis and in the
      defense against intestinal pathogens. Given their close relationship with the gut
      and airway epithelial barriers, ILC are in the first line of defense against a
      number of pathogens but they also need to be tightly regulated in order to avoid
      chronic inflammation. 

PMID- 24685220
TI  - [Circulating miRNAs as a new class of biomedical markers].
AB  - Search for new biomarkers able to improve patient diagnosis has become a real
      challenge in the era of personalized medicine. Considering that early detection
      of cancer greatly increases the chances for successful treatment, the
      identification of accurate biomarkers is essential. In addition, the possibility
      to optimize patients' care and follow-up using "companion" diagnostic tests is
      emerging under the term of theranostics and should become a key step in future
      therapeutics. Since their discovery in serum and their close associations with
      pathological conditions, miRNA found in biological fluids represent a new
      promising class of potential biomarkers. First identified in cancer patients,
      possible applications are very broad and address the vast majority of human
      diseases. This review focuses on recent advances in our knowledge of circulating
      miRNA. Their production in cells, export in extra-cellular environment and
      presumed physiological functions are addressed. The review also emphasizes their
      potential applications in clinics as biomarkers or therapeutic agents. 

PMID- 24685221
TI  - [Beyond usual functions of snoRNAs].
AB  - Small nucleolar RNAs or snoRNAs, principally implicated in post-transcriptional
      chemical modification of other RNAs, were among the first non-coding RNA
      identified, together with ribosomal and transfer RNA. Lately, snoRNA have been
      involved in various unexpected functions, which renewed researcher's interest for
      these molecules. SnoRNA processing into smaller functional RNA species (sdRNA for
      snoRNA-derived RNA) or into miRNA (sno-miR), snoRNA mediated regulation of
      messenger RNA alternative splicing or snoRNA links to human disorders, including
      cancers, are some of the topics developed in this review.

PMID- 24685222
TI  - [Coronary stents: 30 years of medical progress].
AB  - The history of interventional cardiology has been marked by several technologic
      revolutions since the late 1970s. The first key step was the use of inflatable
      balloon angioplasty as an alternative to CABG surgery for coronary
      revascularization, followed by intracoronary delivery of bare metal stent (BMS)
      and drug eluting stents (DES) to drastically reduce intracoronary restenosis
      observed with BMS. Improved stents platforms and polymers (absorbable or
      biocompatible) led to a dramatic reduction in the rate of late stent thrombosis.
      Self-expanding stents are now available to improve stent a position especially in
      acute myocardial infarction. The emergence of new fully bioabsorbable stents that
      can be combined with antiproliferative drugs is the ongoing revolution. A new
      generation of stents is continuously improving and likely to become the ideal
      stent for coronary revascularization in the near future.

PMID- 24685223
TI  - [Experiences and knowledge exchanged in medical consultations by post (16th-18th
      centuries)].
AB  - Consultations by post make up together a significant part of the medical
      literature, especially between the 16(th) and 18(th) centuries and bring
      irreplaceable testimonies on how physicians could follow up their patients from
      far away, in relation with local practitioners who were at their patients'
      bedside or who could visit them on a regular basis. These testimonies are of a
      scientific nature since they show how illustrious physicians diagnosed, predicted
      and prescribed, such as Fernel, Chirac and later on Barthez and Tissot, or less
      famous practitioners such as Le Thieullier, for instance. They are of a literary
      nature since every physician has his own writing style, and the lay out of their
      letters often respects codes. They are of an anthropological nature in the sense
      that a conception of man, ill, with his character, his own life, is rendered
      under the form of narratives.

PMID- 24685224
TI  - [Search for natural substances with therapeutic activity: George R. Pettit].
AB  - This series of brief reviews covers the "life and work" of famous and iconic
      researchers who discovered major therapeutics from natural products: their life
      history, the circumstances of their discoveries, the molecules and their
      molecular, cellular and physiological mechanisms of action, and their biomedical
      applications. Dedicated to George R. Pettit, the second article reviews the life
      of the famous researcher, his worldwide exploration of natural products,
      especially of marine origin, in search of promising anticancer leads, his
      discovery and structural elucidation of very potent drug candidates, their
      synthesis and the launch of some of them on the pharmaceutical market. An
      extraordinary scientific career which lead George R. Pettit from exploration of
      Nature to state-of-the-art analytical and synthetic chemistry and from clinical
      trials to therapeutic successes. 

PMID- 24685225
TI  - [Pithovirus sibericum: awakening of a giant virus of more than 30,000 years].

PMID- 24685226
TI  - Differential influence of 5-HTTLPR - polymorphism and COMT Val158Met -
      polymorphism on emotion perception and regulation in healthy women.
AB  - Converging evidence indicates that a considerable amount of variance in self
      estimated emotional competency can be directly attributed to genetic factors. The
      current study examined the associations between the polymorphisms of the Catechol
      O-methyltransferase (COMT Met158Val) and the serotonin transporter (5-HTTLPR) and
      specific measures of the self-estimated effectiveness of an individual's emotion
      perception and regulation. Emotional competence was measured in a large sample of
      289 healthy women by using the Self-report Emotional Ability Scale (SEAS), which
      includes two subscales for the assessment of emotion perception and regulation in
      the intra-personal domain and two subscales for the assessment of emotion
      perception and regulation in the inter-personal domain. Participants' reports of
      effective emotion regulation in everyday life were associated with the COMT Met
      allele, with women homozygous for the Val-allele scoring lowest on this scale.
      Self-estimated effectiveness of emotion perception of the individual's own
      emotions was related to the 5-HTTLPR. Both homozygous groups (s/s and l/l) rated
      their intra-personal emotion perception less effective than participants in the
      heterozygous s/l group. Taken together, the results indicate that genetic
      variants of the COMT and 5HTTLPR genes are differentially associated with
      specific measures of the self-estimated effectiveness of an individual's emotion
      perception and regulation in the intra-personal domain.

PMID- 24685227
TI  - Clinical course after five years of insulin therapy in patients with type 2
      diabetes in Spain: results of the EDIN study.
AB  - OBJECTIVES: The primary study objective was to assess the proportion of patients
      with type 2 diabetes and an HbA1c value <= 6.5% from the start of insulin therapy
      to five years later in the outpatient setting in Spain. MATERIAL AND METHODS:
      This was an observational, multicenter, naturalistic study with retrospective
      collection of clinical data. Investigators were endocrinologists or internal
      medicine specialists from all over Spain. During standard clinical care, patients
      started insulin therapy, which was continued for at least 5 years. RESULTS: The
      clinical records of 405 patients were reviewed. The final analysis set included
      records from 346 patients. At baseline (start of insulin therapy), 51.2% of
      patients were female; mean (SD) age was 64.6 (9.0) years; body mass index, 29.8
      (4-5) kg/m(2); time since diagnosis, 8.8 (6.8) years; HbA1c, 9.4% (1.5); fasting
      glucose, 223.7 (55.9) mg/dL; and mean 2-hour postprandial glucose, 293.6 (71.0)
      mg/dL. When insulin therapy was started, <1.0% of patients had an HbA1c value <=
      6.5%. At 5 years, 10.3% of patients achieved the HbA1c goal of <= 6.5% (mean,
      7.72%). All glucose parameters (HbA1c, fasting glucose, and 2-hour postprandial
      glucose) improved at 5 years as compared to values at the start of insulin
      therapy. CONCLUSIONS: Glucose parameters improved over time in patients with type
      2 diabetes in this naturalistic study. However, blood glucose control exceeded
      the internationally recommended target values. These results therefore suggest
      that there is still some margin for improvement in outpatient care in Spain.

PMID- 24685229
TI  - Colored dissolved organic matter signature and phytoplankton response in a
      coastal ecosystem during mesoscale cyclonic (cold core) eddy.
AB  - Chromophoric dissolved organic matter (CDOM) and hydrochemical parameters were
      measured in the nearshore region of the western Bay of Bengal with and without
      significant terrestrial influence. A meso-scale cyclonic eddy that occupied the
      northern part of the study area set up a nutrient enriched distinct ecosystem in
      April (premonsoon) attended with increased levels of DOM fluorescence,
      particularly the protein tyrosine like fluorescence (B). A new (minor)
      fluorescence component, attributed to land source was revealed which contained
      two fluorophores, the red-shifted tryptophan-like (TU) hypothesized as the
      "unfolded protein" and the petroleum hydrocarbon-like (P). During the eddy,
      pennate diatom population increased, bringing the centric:pennate diatom ratio to
      half of what it was during the remaining period (monsoon season). The nutrients
      distribution suggested that when pennates are favored (premonsoon),
      orthophosphate and silicate are the limiting nutrients and that when centric
      diatoms are favored (monsoon season), the limitation is by nitrate. 

PMID- 24685228
TI  - Nutrient control of Drosophila longevity.
AB  - Dietary restriction (DR) extends the lifespan of many animals, including
      Drosophila melanogaster. Recent work with flies shows that longevity is
      controlled by the ratio of consumed protein relative to carbohydrates. Given that
      reduced insulin and/or insulin-like growth factor (IGF) and target of rapamycin
      (TOR) signaling increase Drosophila lifespan, these pathways are candidate
      mediators of DR. However, this idea has ambiguous experimental support. The
      Nutritional Geometric Framework (NGF), which dissects the impact of nutrient
      protein relative to carbohydrates, may provide an approach to resolving the roles
      for these pathways in DR. Nutrient sensing of protein and carbohydrate may occur
      in the fat body through signals to hypothalamic-like neurons in the fly brain
      and, thus, control secretion of insulin-like peptides that regulate longevity.

PMID- 24685230
TI  - [The heart failure patient: a case report].
AB  - Given its prevalence, high mortality rate, morbidity, chronicity and use of
      resources, heart failure (HF) is a priority issue from a social and health
      standpoint, due to the ageing population and to lack of adherence to and the
      complexity of treatment. For these reasons, an individualized care plan needs to
      be established to meet the real and potential needs of the patient diagnosed with
      HF. A clinical case is presented of a patient admitted to the Cardiology Critical
      Care (CCC) unit of a tertiary hospital. A patient care plan was prepared
      following the steps of the scientific method and relying on the NANDA taxonomy,
      and the NOC and NIC to design goals and nursing interventions, respectively.

PMID- 24685231
TI  - beta2-glycoprotein I, lipopolysaccharide and endothelial TLR4: three players in
      the two hit theory for anti-phospholipid-mediated thrombosis.
AB  - The thrombogenic effect of beta2-glycoprotein I (beta2GPI)-dependent anti
      phospholipid antibodies (aPL) in animal models was found to be LPS dependent.
      Since beta2GPI behaves as LPS scavenger, LPS/beta2GPI complex was suggested to
      account for in vitro cell activation through LPS/TLR4 involvement being LPS the
      actual bridge ligand between beta2GPI and TLR4 at least in monocytes/macrophages.
      However, no definite information is available on the interaction among beta2GPI,
      LPS and endothelial TLR4 in spite of the main role of endothelial cells (EC) in
      clotting. To analyse at the endothelial level the need of LPS, we investigated
      the in vitro interaction of beta2GPI with endothelial TLR4 and we assessed the
      role of LPS in such an interaction. To do this, we evaluated the direct binding
      and internalization of beta2GPI by confocal microscopy in living TLR4-MD2
      transfected CHO cells (CHO/TLR4-MD2) and beta2GPI binding to CHO/TLR4-MD2 cells
      and human umbilical cord vein EC (HUVEC) by flow cytometry and cell-ELISA using
      anti-beta2GPI monoclonal antibodies in the absence or presence of various
      concentrations of exogenous LPS. To further investigate the role of TLR4, we
      performed anti-beta2GPI antibody binding and adhesion molecule up-regulation in
      TLR4-silenced HUVEC. Confocal microscopy studies show that beta2GPI does interact
      with TLR4 at the cell membrane and is internalized in cytoplasmic granules in
      CHO/TLR4-MD2 cells. beta2GPI binding to CHO/TLR4-MD2 cells and HUVEC is also
      confirmed by flow cytometry and cell-ELISA, respectively. The interaction between
      beta2GPI and TLR4 is confirmed by the reduction of anti-beta2GPI antibody binding
      and by the up-regulation of E-selectin or ICAM-1 by TLR4 silencing in HUVEC.
      beta2GPI binding is not affected by LPS at concentrations comparable to those
      found in both beta2GPI and antibody preparations. Only higher amount of LPS that
      can activate EC and up-regulate TLR4 expression are found to increase the
      binding. Our findings demonstrate that beta2GPI interacts directly with TLR4
      expressed on EC, and that such interaction may contribute to beta2GPI-dependent
      aPL-mediated EC activation. At variance of monocytic cells, we also showed a
      threshold effect for the action of LPS, that is able to enhance anti-beta2GPI
      antibody EC binding only at cell activating concentrations, shown to increase
      TLR4 expression. This in vitro model may explain why LPS behaves as a second hit
      increasing the expression of beta2GPI in vascular tissues and triggering aPL
      mediated thrombosis in experimental animals. 

PMID- 24685233
TI  - DAFS: a data-adaptive flag method for RNA-sequencing data to differentiate genes
      with low and high expression.
AB  - BACKGROUND: Next-generation sequencing (NGS) has advanced the application of high
      throughput sequencing technologies in genetic and genomic variation analysis. Due
      to the large dynamic range of expression levels, RNA-seq is more prone to detect
      transcripts with low expression. It is clear that genes with no mapped reads are
      not expressed; however, there is ongoing debate about the level of abundance that
      constitutes biologically meaningful expression. To date, there is no consensus on
      the definition of low expression. Since random variation is high in regions with
      low expression and distributions of transcript expression are affected by
      numerous experimental factors, methods to differentiate low and high expressed
      data in a sample are critical to interpreting classes of abundance levels in RNA
      seq data. RESULTS: A data-adaptive approach was developed to estimate the lower
      bound of high expression for RNA-seq data. The Kolmgorov-Smirnov statistic and
      multivariate adaptive regression splines were used to determine the optimal
      cutoff value for separating transcripts with high and low expression. Results
      from the proposed method were compared to results obtained by estimating the
      theoretical cutoff of a fitted two-component mixture distribution. The robustness
      of the proposed method was demonstrated by analyzing different RNA-seq datasets
      that varied by sequencing depth, species, scale of measurement, and empirical
      density shape. CONCLUSIONS: The analysis of real and simulated data presented
      here illustrates the need to employ data-adaptive methodology in lieu of
      arbitrary cutoffs to distinguish low expressed RNA-seq data from high expression.
      Our results also present the drawbacks of characterizing the data by a two
      component mixture distribution when classes of gene expression are not well
      separated. The ability to ascertain stably expressed RNA-seq data is essential in
      the filtering process of data analysis, and methodologies that consider the
      underlying data structure demonstrate superior performance in preserving most of
      the interpretable and meaningful data. The proposed algorithm for classifying low
      and high regions of transcript abundance promises wide-range application in the
      continuing development of RNA-seq analysis.

PMID- 24685234
TI  - Life-threatening cardiac tamponade: a rare complication of acupuncture.
AB  - Acupuncture as an ancient Chinese treatment has proven effective and is utilized
      worldwide. Although it is generally believed to be a safe clinical procedure,
      serious lethal complications including death have been reported. We present a
      rare case of life-threatening cardiac tamponade due to penetration of an
      acupuncture needle directly into the right ventricle. 

PMID- 24685232
TI  - Hormonal milieu at time of B cell activation controls duration of autoantibody
      response.
AB  - A strong gender bias is seen in many autoimmune diseases including systemic lupus
      erythematosus (SLE). To investigate the basis for the female preponderance in
      SLE, we have been studying BALB/c mice in which B cells express the R4A heavy
      chain of an anti-DNA antibody in association with an endogenous light chain
      repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells
      express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum
      titers of anti-DNA antibodies. Administration of either estradiol (E2) or
      prolactin (Pr) results in escape from tolerance of autoreactive B cells,
      expressed as an increase in transgene-expressing B cells and elevated serum
      titers of anti-DNA antibodies. We previously demonstrated that autoreactive B
      cells maturing in an estrogenic milieu develop as marginal zone (MZ) B cells;
      when these same B cells mature in the presence of increased prolactin, they
      develop as follicular (Fo) B cells. To determine the long term consequence of
      this differential maturation of DNA-reactive B cells, we treated R4Atg BALB/c
      mice with E2 or Pr for 6 weeks until serum titers of anti-DNA antibody were high,
      at which time hormonal exposure was discontinued. In E2-treated mice, the anti
      DNA titers remained high even 3 months after discontinuation of hormone exposure.
      Nascent B cells underwent normal tolerance induction, but existing autoreactive
      MZ B cells persisted and continued to secrete autoantibody. In contrast, Pr
      caused only a short-term increase in anti-DNA antibody titers. By 3 months after
      cessation of hormone treatment, serum anti-DNA antibody titers and B cell subsets
      were indistinguishable from those in placebo (P) treated mice. These findings
      suggest that autoantibody responses are sustained for variable lengths of time
      depending on the B cell subset producing the autoantibodies. This observation may
      be relevant to understanding the heterogeneous presentation of patients with SLE
      and to the design of therapies targeting specific B-cell populations in
      autoimmune disease. 

PMID- 24685235
TI  - Trabeculectomy with versus without releasable sutures for glaucoma: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and tolerability of
      trabeculectomies performed with and without releasable sutures in the treatment
      of patients with uncontrolled glaucoma. METHODS: A comprehensive literature meta
      analysis was performed, comparing trabeculectomies performed with and without
      releasable sutures. The primary efficacy measure was the weighted mean difference
      (WMD) in percentage intraocular pressure reduction (IOPR%) at the follow-up end
      point. The secondary efficacy measure was the risk ratio (RR) for complete and
      qualified success rates of trabeculectomy at the follow-up end point.
      Trabeculectomy tolerability estimates were measured by the RR for adverse events.
      All the outcomes were reported with a 95% confidence interval (CI). RESULTS: The
      WMD of the IOPR% from baseline was -4.56 (range -9.24-0.12) when trabeculectomies
      without releasable sutures were compared with trabeculectomies with releasable
      sutures. Trabeculectomies with releasable sutures were associated with
      numerically greater, but nonsignificant, efficacy in terms of lowered IOP
      compared with trabeculectomies without releasable sutures. The complete and
      qualified success rate of the two surgical procedures were comparable, with RRs
      of 0.92 (range 0.80-1.04) and 0.99 (range 0.89-1.11), respectively, at the follow
      up endpoints. Trabeculectomies without releasable sutures were associated with a
      significantly higher frequency of hypotony and flat anterior chambers than
      trabeculectomies with releasable sutures, with pooled RRs of 4.04 (range 1.88
      8.68) and 2.57 (range 1.25-5.30), respectively. CONCLUSION: Although the two
      surgical procedures resulted in equivalent efficacy in IOP control, the
      trabeculectomies performed with releasable sutures were better tolerated than
      those without releasable sutures.

PMID- 24685236
TI  - Vegetable consumption is linked to decreased visceral and liver fat and improved
      insulin resistance in overweight Latino youth.
AB  - There are limited data on the influence of vegetable consumption on adiposity and
      metabolic health, specifically nonstarchy vegetables and vegetables that are dark
      green and deep orange/yellow (also known as nutrient-rich vegetables). Our study
      examines the relationship between vegetable intake and adiposity, liver fat, and
      insulin dynamics in overweight Latino youth. This cross-sectional study of 175
      overweight (body mass index >=85th percentile) Latino youth (aged 8 to 18 years),
      with data collected during 2006-2011, included the following: dietary intake via
      multiple 24-hour recalls, total body fat via dual-energy x-ray absorptiometry,
      adipose tissue distribution and liver fat via magnetic resonance imaging, and
      insulin dynamics via frequently sampled intravenous glucose tolerance test.
      Linear regression and analysis of covariance were used for analysis, with the
      following a priori covariates: age, sex, energy intake, and total body fat.
      Participants who consumed the most nonstarchy vegetables (mean intake=1.7+/-1.0
      servings/day) compared with the least (mean intake=0.1+/-0.1 servings/day) had
      44% less liver fat (10.0%+/-8.5% vs 5.6%+/-8.7%; P=0.01). Nutrient-rich vegetable
      intake was positively correlated with insulin sensitivity (r=0.19; P=0.03).
      Consumers of nutrient-rich vegetables (mean intake=0.3+/-0.4 servings/day
      [n=107]), compared with nonconsumers (n=68), had 31% increased insulin
      sensitivity (1.6+/-1.6 vs 2.1+/-1.3*10(-4)/min/MUU/mL; P=0.03) and 17% less
      visceral adipose tissue (2.3+/-0.9 vs 1.9+/-0.7 L; P=0.01). Consumption of
      specific vegetable types by overweight Latino youth is associated with positive
      metabolic outcomes, including reduced visceral and liver fat and risk factors for
      type 2 diabetes, even when consumed in small quantities. These may be relevant
      targets for interventions.

PMID- 24685237
TI  - Identifying association model for single-nucleotide polymorphisms of ORAI1 gene
      for breast cancer.
AB  - BACKGROUND: ORAI1 channels play an important role for breast cancer progression
      and metastasis. Previous studies indicated the strong correlation between breast
      cancer and individual single nucleotide polymorphisms (SNPs) of ORAI1 gene.
      However, the possible SNP-SNP interaction of ORAI1 gene was not investigated.
      RESULTS: To develop the complex analyses of SNP-SNP interaction, we propose a
      genetic algorithm (GA) to detect the model of breast cancer association between
      five SNPs (rs12320939, rs12313273, rs7135617, rs6486795 and rs712853) of ORAI1
      gene. For individual SNPs, the differences between case and control groups in
      five SNPs of ORAI1 gene were not significant. In contrast, GA-generated SNP
      models show that 2-SNP (rs12320939-GT/rs6486795-CT), 3-SNP (rs12320939
      GT/rs12313273-TT/rs6486795-TC), 5-SNP (rs12320939-GG/rs12313273-TC/rs7135617
      TT/rs6486795-TT/rs712853-TT) have higher risks for breast cancer in terms of odds
      ratio analysis (1.357, 1.689, and 13.148, respectively). CONCLUSION: Taken
      together, the cumulative effects of SNPs of ORAI1 gene in breast cancer
      association study were well demonstrated in terms of GA-generated SNP models.

PMID- 24685238
TI  - Phylogeny of Spanish swine influenza viruses isolated from respiratory disease
      outbreaks and evolution of swine influenza virus within an endemically infected
      farm.
AB  - In the present study, outbreaks of respiratory disease were investigated for the
      presence of swine influenza virus (SIV). In 14 cases the circulating SIV strains
      were isolated, fully sequenced and compared with other known SIVs. The viruses
      causing the outbreaks belonged to the H1N1 (including human pandemic H1N1), H3N2
      and H1N2 subtypes. In 11/14 cases the phylogenetic analyses indicated the
      occurrence of probable reassortment events. In the second part of the study, the
      genetic evolution of H1N1 SIV was assessed in a longitudinal study in closed
      groups of pigs over six months. Sequencing of the 22 isolates indicated co
      circulation of two different variants for the same virus, as well as the
      emergence of SIV reassortants at certain time-points. These results indicate that
      reassortment events in SIV are common, and point towards the need for a better
      understanding of the epidemiology of SIV, particularly in endemic farms. 

PMID- 24685240
TI  - Brucella suis in armadillos (Chaetophractus villosus) from La Pampa, Argentina.
AB  - Brucellosis is a zoonotic disease transmitted from an animal reservoir to humans.
      Both, wildlife and domestic animals, contribute to the spreading of these
      zoonosis. The surveillance of the animal health status is strictly regulated for
      domestic animals, whereas disease monitoring in wildlife does not exist. The aim
      of the present study was to provide data on the prevalence of anti-Brucella
      antibodies in Chaetophractus villosus from a region of La Pampa, Argentina to
      assess public health risks. The C. villosus is endemic to South America, and in
      Argentina it represents a food resource for human consumption. A total of 150
      sera of armadillos bleeding between 2007 and 2010 were tested using buffered
      plate antigen test (BPAT), serum agglutination test (SAT), 2-mercaptoethanol (2
      ME) and complement fixation test (CFT), for the detection of anti-Brucella
      antibodies. Antibodies to Brucella sp. were found in 16% (24:150) of the
      armadillos tested using the BPAT test. All 24 positive samples were confirmed by
      the SAT, 2-ME and CFT tests. Strain isolation was attempted from liver and spleen
      samples of two animals with positive serology. Isolates were characterized by
      conventional biotyping and identification of specific DNA using polymerase chain
      reaction (PCR). A total of 2 isolates were recovered from spleen and liver. Both
      of them were identified as Brucella suis biovar 1. This preliminary study
      provides the first report on the seroprevalence of brucellosis and describes the
      first isolate of B. suis biovar 1 in C. villosus in Argentina. 

PMID- 24685239
TI  - Quality control ranges for cefoperazone 30 MUg disks for Staphylococcus aureus
      ATCC(r) 25923 and Escherichia coli ATCC(r) 25922.
AB  - The third generation cephalosporin cefoperazone is commonly used for bovine
      mastitis therapy. So far, the cefoperazone susceptibility testing using 30 MUg
      disks was hampered by the lack of quality control (QC) ranges and the respective
      interpretive criteria. The aim of this study was to develop CLSI-approved QC
      ranges for Staphylococcus aureus ATCC((r)) 25923 and Escherichia coli ATCC((r))
      25922. An interlaboratory trial including eight laboratories was conducted. Each
      laboratory tested both QC reference strains ten times using two lots of
      cefoperazone 30 MUg disks and three lots of Mueller-Hinton agar. The results were
      analysed by using the published statistical analysis method. Based on the data,
      zone diameters of 23-34 mm and 24-33 mm were established as QC ranges for the 30
      MUg disk and S. aureus ATCC((r)) 25923 and E. coli ATCC((r)) 25922, respectively.
      These new QC ranges have been recently approved by the Clinical and Laboratory
      Standards Institute and will help diagnostic laboratories to validate their
      cefoperazone testing results using 30 MUg disks.

PMID- 24685241
TI  - Caspian White Fish (Rutilus frisii kutum) as a host for Spring Viraemia of Carp
      Virus.
AB  - Rutilus frisii kutum is a fish of the Cyprinidae Family which is native in
      Caspian Sea and commercially cultured in Iran. This study was conducted to
      investigate susceptibility of Caspian White Fish to Spring Viraemia of Carp Virus
      (SVCV) infection and to evaluate influence of different challenge routes on
      virulence of the virus. Fingerlings were infected by immersion, intra-peritoneal
      (i.p.) injection, cohabitation and orally. Dead and surviving fish were collected
      for histological examination as well as for virus re-isolation by cell culture,
      Reverse Transcriptase Polymerization Chain Reaction (RT-PCR) and Indirect
      Fluorescent Antibody Test (IFAT) analysis. The results indicated that immersion
      was the best infectious route of transmission with the highest mortality, whereas
      oral transmission showed the lowest mortality. The virus was also re-isolated
      from dead fish and identified by IFAT. In addition, histopathological changes
      including branchial, hepatic and splenic necrosis as well as glomerulonephritis
      and necrosis in kidney were observed in diseased fish tissues but not in the
      survivors. RT-PCR on samples obtained from surviving fish tissues detected viral
      genome in the fish surviving from immersion, i.p. injection and cohabitation
      challenges but not in the fish infected orally. In conclusion, Caspian White Fish
      are susceptible to infection by SVCV and virulence of the virus could be
      influenced by route of transmission. In addition, SVCV could persist in surviving
      fish, which may serve as reservoirs of the virus, transmitting infection to
      healthy fish population. 

PMID- 24685242
TI  - Expression of microRNA-454 in TGF-beta1-stimulated hepatic stellate cells and in
      mouse livers infected with Schistosoma japonicum.
AB  - BACKGROUND: In the process of hepatic fibrosis, hepatic stellate cells (HSCs) can
      be activated by many inflammatory cytokines. The transforming growth factor-beta1
      (TGF-beta1) is one of the main profibrogenic mediators. Recently, some studies
      have also shown that microRNAs (miRNAs) play essential roles in the progress of
      liver fibrosis by being involved in the differentiation, fat metabolism and ECM
      production of HSCs. METHODS: The expression of miR-454 in LX-2 cells treated with
      TGF-beta1 and in the fibrotic livers with Schistosoma japonicum infection was
      detected by qRT-PCR. The role of miR-454 on LX-2 cells was then analyzed by
      Western blot, flow cytometry and luciferase assay. RESULTS: The results showed
      that the expression of miR-454 was down-regulated in the TGF-beta1-treated LX-2
      cells and miR-454 could inhibit the activation of HSCs by directly targeting
      Smad4. However, we found that miR-454 had no effect on cell cycle and cell
      proliferation in TGF-beta1-treated LX-2. Besides these, miR-454 was found to be
      regulated in the process of Schistosoma japonicum infection. CONCLUSIONS: All the
      results suggested that miR-454 could provide a novel therapeutic approach for
      treating liver fibrosis, especially the liver fibrosis induced by Schistosoma
      japonicum.

PMID- 24685243
TI  - Nanosuspension delivery of paclitaxel to xenograft mice can alter drug
      disposition and anti-tumor activity.
AB  - Paclitaxel is a common chemotherapeutic agent that is effective against various
      cancers. The poor aqueous solubility of paclitaxel necessitates a large
      percentage of Cremophor EL:ethanol (USP) in its commercial formulation which
      leads to hypersensitivity reactions in patients. We evaluate the use of a
      crystalline nanosuspension versus the USP formulation to deliver paclitaxel to
      tumor-bearing xenograft mice. Anti-tumor efficacy was assessed following
      intravenous administration of three 20 mg/kg doses of paclitaxel. Paclitaxel
      pharmacokinetics and tissue distribution were evaluated, and differences were
      observed between the two formulations. Plasma clearance and tissue to plasma
      ratio of mice that were dosed with the nanosuspension are approximately 33- and
      11-fold higher compared to those of mice that were given the USP formulation.
      Despite a higher tumor to plasma ratio for the nanosuspension treatment group,
      absolute paclitaxel tumor exposure was higher for the USP group. Accordingly, a
      higher anti-tumor effect was observed in the xenograft mice that were dosed with
      the USP formulation (90% versus 42% tumor growth inhibition). This reduction in
      activity of nanoparticle formulation appeared to result from a slower than
      anticipated dissolution in vivo. This study illustrates a need for careful
      consideration of both dose and systemic solubility prior utilizing nanosuspension
      as a mode of intravenous delivery. 

PMID- 24685244
TI  - A new algorithm for quadratic sample entropy optimization for very short
      biomedical signals: application to blood pressure records.
AB  - This paper describes a new method to optimize the computation of the quadratic
      sample entropy (QSE) metric. The objective is to enhance its segmentation
      capability between pathological and healthy subjects for short and unevenly
      sampled biomedical records, like those obtained using ambulatory blood pressure
      monitoring (ABPM). In ABPM, blood pressure is measured every 20-30 min during 24h
      while patients undergo normal daily activities. ABPM is indicated for a number of
      applications such as white-coat, suspected, borderline, or masked hypertension.
      Hypertension is a very important clinical issue that can lead to serious health
      implications, and therefore its identification and characterization is of
      paramount importance. Nonlinear processing of signals by means of entropy
      calculation algorithms has been used in many medical applications to distinguish
      among signal classes. However, most of these methods do not perform well if the
      records are not long enough and/or not uniformly sampled. That is the case for
      ABPM records. These signals are extremely short and scattered with outliers or
      missing/resampled data. This is why ABPM Blood pressure signal screening using
      nonlinear methods is a quite unexplored field. We propose an additional stage for
      the computation of QSE independently of its parameter r and the input signal
      length. This enabled us to apply a segmentation process to ABPM records
      successfully. The experimental dataset consisted of 61 blood pressure data
      records of control and pathological subjects with only 52 samples per time
      series. The entropy estimation values obtained led to the segmentation of the two
      groups, while other standard nonlinear methods failed.

PMID- 24685245
TI  - Molecular typing of human platelet and neutrophil antigens (HPA and HNA).
AB  - Genotyping is an important tool in the diagnosis of disorders involving allo
      immunisation to antigens present on the membranes of platelets and neutrophils.
      To date 28 human platelet antigens (HPAs) have been indentified on six
      polymorphic glycoproteins on the surface of platelets. Antibodies against HPAs
      play a role in foetal and neonatal alloimmune thrombocytopenia (FNAIT), post
      transfusion purpura (PTP) and refractoriness to donor platelets. The 11 human
      neutrophil antigens (HNAs) described to date have been indentified on five
      polymorphic proteins on the surface of granulocytes. Antibodies to HNAs are
      implicated with foetal and neonatal alloimmune neutropenia (FNAIN), autoimmune
      neutropenia (AIN) and transfusion related acute lung injury (TRALI). In this
      report, we will review the molecular basis and techniques currently available for
      the genotyping of human platelet and neutrophil antigens. 

PMID- 24685246
TI  - [Editorial. The orthodontist and beauty].

PMID- 24685247
TI  - [Beauty judgment: review of the literature].
AB  - Esthetic judgments are surely subjective, but as surely, that does not preclude
      them being studied objectively through rigorous scientific methods. The factual
      basis of a science of esthetics is not to settle whether some person or image is
      "objectively beautiful" but rather to determine whether some representative set
      or sets of individuals judge or experience him/her/it as beautiful or
      unattractive. The aim of this paper is to review the definitional, theoretical
      and methodological aspects pertaining to the perception of facial/dental
      attractiveness by a group of representative individuals. The first part lays down
      the basic principles of the perception of facial/dental attractiveness: the
      perception involves a jury, a field of investigation and a test providing
      quantitative data; the following general determinants of beauty perception are
      reviewed: the average morphology, the judge's cultural background, the
      numerology, the judge's ethnical origin. Indirect determinants are the dentition,
      the osseous architecture and the muscular envelope. Some disruptive factors might
      alter the judges' facial perception. They might be qualified as either peripheral
      to the face or psycho-social factors. Peripheral factors include hair style and
      color, skin hue, wrinkles, lips color... Psycho-social factors cover the
      personality of the subject being evaluated, his/her intelligence or behavior. The
      second part deals specifically with the methodology used to determine facial
      attractiveness and to correlate this latter with a specific morphology. Typically
      such a study aims to determine average esthetic preferences for some set of
      visual displays among a particular jury, given a specific task to judge esthetic
      quality or qualities. The sample being studied, the displays, the jury or jurys,
      the rating procedure must all be specified prior to collecting data. A specific
      emphasis will be given to the rating process and the associated morphometrics,
      the ultimate goal being to discriminate morphologies judged as attractive among
      our patients. 

PMID- 24685248
TI  - [Orthognathic surgery in adults: state of the art].
AB  - The objective of orthognathic surgery is the repositioning of the osseous bases
      of the jaws. Its consequences are both aesthetic and functional. As adults are
      increasingly concerned with appearance, orthognathic surgery is today, more than
      ever, a close collaboration between the orthodontist, surgeon and general
      dentist. The whole team must be capable of coordinating its approach with an
      aesthetic objective. For the surgeon, a perfect knowledge of complementary
      techniques (rhinoplasty, bone grafts, plastic surgery of the face, lipostructure
      or fillers) makes orthognathic surgery a completely separate surgical speciality.
      The aim of this article is to establish the philosophy underlying this type of
      treatment and define relevant fundamental aspects. We propose an esthetic "extra
      oral" clinical approach not focused on occlusal anomalies but on classification
      of tooth positional abnormalities in the smile and the therapeutic options that
      we have for placing teeth in correct positions in the smile. 

PMID- 24685249
TI  - [Contribution of three dimensional cephalometry in the study of determining
      morphological parameters for facial esthetics].
AB  - There have been numerous studies of facial esthetics, but few have benefited from
      the new techniques provided by 3D imaging. The aim of this study is to determine
      which are the most crucial cephalometric criteria for facial esthetics by
      identifying the strongest correlations between the esthetic rating and 3D
      Cephalometric values, the Cepha 3Dt. A group of 91 subjects (from 10 to 60 years
      of age) was rated by a jury of 50 randomly selected judges (from 12 to 65 years
      of age) using an analog scale. We then looked for the most important correlations
      between the esthetic ratings and the tridimensional cephalometric values by using
      3D Cephalometric Analysis on a global sample, and on Class II and Class III sub
      samples. Facial esthetics therefore appeared to be especially linked to: anterior
      posterior dimension, maxillo-mandibular disharmony, relationships between the
      anterior areas (alveolar and basal), the alveolar region has a greater impact
      than the basal area on facial architecture. In the Class II group, sagittal
      discrepancies and mandibular divergence have an equal impact on the assessment of
      facial esthetics. 

PMID- 24685250
TI  - [Invisible and almost invisible orthodontic appliances].
AB  - Patient demand for invisible esthetic orthodontic appliances is steadily
      increasing. Two types of orthodontic appliances have a high rate of patient
      acceptance. The lingual technique has continually evolved by offering both
      prefabricated brackets or custom-made brackets. The various techniques have been
      improved over time, and the results are better than ever. Thermoplastic aligners
      are an alternative to lingual devices and their use is rapidly growing. Their
      specific properties make it easier to assess their indications and limitations. A
      review of the literature, the development of these systems and a presentation of
      some clinical examples of treated cases will help us to provide some of the
      basics for understanding each of these two types of appliances and to demonstrate
      the advantages and disadvantages of each system. 

PMID- 24685251
TI  - [Finishing and detailing, stability and harmony].
AB  - The finishing and detailing phase, the last stage of active orthodontic
      treatment, makes it possible to perfect the occlusion, by adhering to criteria
      defined by various authors and to improve the esthetic result, while achieving
      the treatment objectives made during the pre-planning phase. The reliability of
      end of treatment results cannot be ensured without an initial individualized
      analysis of the risk factors for relapse specific to each patient. It is only
      after this analysis, that the orthodontist will be able to determine how to
      comply with these criteria for stability, common in any treatment, and to
      individually choose and implement reliable procedures. When planning for
      stability as the treatment objective, orthodontic patients are able to achieve
      stable alignment. This course of action is the necessary process to help ensure
      equilibrium and alignment. Eight different methods of alignment, already
      frequently discussed in the literature, will be described and analyzed in this
      paper. 

PMID- 24685252
TI  - [What makes a pleasing face].
AB  - Regular faces are beautiful because they are expressive and arouse an interest in
      the observer due to the variations in their shape, their surface appearance and
      their movements. The sensitivity of the eye of the beholder is correlated to the
      expressivity of the face and of the dentition. Better, however, to avoid any
      indication of aggression that could foreshadow the senescence of the face. 

PMID- 24685253
TI  - [Beauty and esthetics: juridical approach].
AB  - Although beauty is increasingly becoming a right mostly as it relates to objects,
      people are now beginning to make a new demand - the right to personal beauty: the
      right to live in and surrounded by beauty and the right to be beautiful. 

PMID- 24685254
TI  - Impact of vitamin D supplementation on health-care use in a 25-hydroxyvitamin D
      tested population in France: a population-based descriptive cohort study.
AB  - OBJECTIVE: Chronic vitamin D deficiency has been associated in some patients with
      diffuse musculoskeletal pain. These unspecific symptoms may partly explain why
      vitamin D deficiency is often diagnosed late. Our aim was to analyse health-care
      claims after vitamin D supplementation in patients likely to have vitamin D
      deficiency. DESIGN: Ambulatory health-care claims were compared before and after
      a vitamin D supplementation prescribed following a 25-hydroxyvitamin D assay.
      SETTING: Health Insurance Fund (FHIF) database of the Rhone-Alpes area, France.
      SUBJECTS: Among patients reimbursed for a 25-hydroxyvitamin D assay between 1
      December 2008 and 31 January 2009, those supplemented with vitamin D after the
      assay were matched on the date of assay to patients who did not receive vitamin
      D. RESULTS: Among the 3023 patients who had a 25-hydroxyvitamin D assay, 935 were
      consequently supplemented and matched to 935 patients not supplemented. Their
      median age was 50.0 and 49.5 years, respectively. Patients supplemented decreased
      their muscle relaxant consumption whereas no change was observed in the reference
      group, the difference between the two groups was significant (P=0.03). Second and
      third Pain Relief Ladder prescriptions decreased in both groups but not
      significantly differently between groups (P=0.58). There was a decrease in
      prescriptions of biological examination in both groups with no significant
      difference. CONCLUSIONS: Besides a decrease in muscle relaxant prescriptions in
      the supplemented group, it was difficult to assess the impact of vitamin D
      supplementation in patients likely to have vitamin D deficiency. Prospective
      cohort studies and randomized trials are needed to assess the efficiency of
      screening and supplementing vitamin D deficiency.

PMID- 24685255
TI  - Antihypertensive drug treatment changes in the general population: the CoLaus
      study.
AB  - BACKGROUND: Changes in antihypertensive drug treatment are paramount in the
      adequate management of patients with hypertension, still, there is little
      information regarding changes in antihypertensive drug treatment in Switzerland.
      Our aim was to assess those changes and associated factors in a population-based,
      prospective study. METHODS: Data from the population-based, CoLaus study,
      conducted among subjects initially aged 35-75 years and living in Lausanne,
      Switzerland. 772 hypertensive subjects (371 women) were followed for a median of
      5.4 years. Data Subjects were defined as continuers (no change), switchers (one
      antihypertensive class replaced by another), combiners (one antihypertensive
      class added) and discontinuers (stopped treatment). The distribution and the
      factors associated with changes in antihypertensive drug treatment were assessed.
      RESULTS: During the study period, the prescription of diuretics decreased and of
      ARBs increased: at baseline, diuretics were taken by 46.9% of patients;
      angiotensin receptor blockers (ARB) by 44.7%, angiotensin converting enzyme
      inhibitors (ACEI) by 28.8%, beta-blockers (BB) by 28.0%, calcium channel blockers
      (CCB) by 18.9% and other antihypertensive drugs by 0.3%. At follow-up
      (approximately 5 years later), their corresponding percentages were 42.8%, 51.7%,
      25.5%, 33.0% 20.7% and 1.0%. Among all participants, 54.4% (95% confidence
      interval: 50.8-58.0) were continuers, 26.9% (23.8-30.2) combiners, 12.7% (10.4
      15.3) switchers and 6.0% (4.4-7.9) discontinuers. Combiners had higher systolic
      blood pressure values at baseline than the other groups (p < 0.05). Almost one
      third (30.6%) of switchers and 29.3% of combiners improved their blood pressure
      status at follow-up, versus 18.8% of continuers and 8.7% of discontinuers (p <
      0.001). Conversely, almost one third (28.3%) of discontinuers became hypertensive
      (systolic >=140 mm Hg or diastolic >=90 mm Hg), vs. 22.1% of continuers, 16.3% of
      switchers and 11.5% of combiners (p < 0.001). Multivariate analysis showed
      baseline uncontrolled hypertension, ARBs, drug regimen (monotherapy/polytherapy)
      and overweight/obesity to be associated with changes in antihypertensive therapy.
      CONCLUSION: In Switzerland, ARBs have replaced diuretics as the most commonly
      prescribed antihypertensive drug. Uncontrolled hypertension, ARBs, drug regimen
      (monotherapy or polytherapy) and overweight/obesity are associated with changes
      in antihypertensive treatment.

PMID- 24685256
TI  - Gamma probe-assisted excision of an ectopic parathyroid adenoma located within
      the thymus: case report and review of the literature.
AB  - Primary hyperparathyroidism due to parathyroid adenomas may be associated with
      ectopic parathyroid gland localization in 20-25% of the patients. We report
      herein the excision of an ectopic parathyroid adenoma which was detected in the
      thymus gland by gamma probe intraoperatively. A 38-year-old patient presented to
      our clinic with a history of bilateral nephrolithiasis, chronic hypercalcaemia,
      and PTH elevation. A combination of Technetium-99 m sestamibi scintigraphy and
      Computed Tomography scan of the chest and neck revealed an ectopic parathyroid
      adenoma of 8.5 mm in its greatest dimension. The patient underwent sternotomy and
      the adenoma was found within the right lobe of the thymus gland with the
      intraoperative use of gamma probe. PTH detection and frozen biopsy were performed
      during surgery and confirmed the successful excision of the adenoma, while mild
      hypocalcaemia was noticed postoperatively. We conclude that accurate preoperative
      and intraoperative localization of an ectopic parathyroid adenoma is crucial to
      successful surgery. The use of at least two diagnostic modalities before surgical
      excision minimizes the risk of re-operation for recurrent hyperparathyroidism,
      while the intraoperative use of gamma probe offers a significant advantage over
      conventional techniques by reducing surgical time, morbidity and/or complications
      associated with surgical exploration. 

PMID- 24685257
TI  - Assessment of the effect of iris colour and having children on 5-year risk of
      death after diagnosis of uveal melanoma: a follow-up study.
AB  - BACKGROUND: To examine the all-cause mortality and uveal melanoma specific
      mortality among newly diagnosed uveal melanoma patients after five years.
      Furthermore, we assess of the effect of iris colour and having children on 5-year
      risk of death after diagnosis of uveal melanoma. Therefore, we assess the
      performance of an individual prediction model of survival from uveal melanoma.
      METHODS: A cohort of 459 patients aged 45 to 79 years with newly diagnosed uveal
      melanoma was recruited between 2002 and 2004 from the Division of Ophthalmology,
      University of Essen, Germany. Survival probabilities were estimated by Kaplan
      Meier survival analysis. The clinical and histopathological characteristics were
      obtained from medical records. Iris colour and childbearing history were assessed
      at baseline by a computer-assisted telephone interview. We used crude and
      multivariable Cox proportional hazards regression to estimate unadjusted and
      adjusted hazard ratios (HR) and corresponding 95% confidence intervals (95%CIs)
      with respect to death from uveal melanoma and death from all causes. We used the
      Cox model to estimate adjusted probabilities of primary events. For computing
      Harrell's C statistics, we used a Cox model including the prognostics factors
      gender, age at diagnosis, ciliary body involvement, largest basal tumour
      diameter, and iris colour. RESULTS: The 5-year uveal melanoma-specific survival
      probability was 82.9% (95% CI: 79.1-86.3). Main prognostic factors for the death
      of uveal melanoma were ciliary body involvement (HR: 1.7 (95% CI:1.0-2.8)),
      largest basal tumour diameter >15 mm HR: 7.0 (95% CI: 3.5-13.9), light iris
      colour (HR: 2.3 (95% CI: 0.9-5.8), having children (HR: 0.6 (95% CI: 0.2 - 1.7)),
      and gender (HR: 0.7 (95% CI: 0.4-1.1)). The value of the bootstrap-corrected C
      statistics was 0.76 (95% CI: 0.74-0.77). CONCLUSION: Beyond the established
      prognostic factors, light iris colour also appears to be a prognostic factor for
      death from uveal melanoma.

PMID- 24685258
TI  - SPiCE: a web-based tool for sequence-based protein classification and
      exploration.
AB  - BACKGROUND: Amino acid sequences and features extracted from such sequences have
      been used to predict many protein properties, such as subcellular localization or
      solubility, using classifier algorithms. Although software tools are available
      for both feature extraction and classifier construction, their application is not
      straightforward, requiring users to install various packages and to convert data
      into different formats. This lack of easily accessible software hampers quick,
      explorative use of sequence-based classification techniques by biologists.
      RESULTS: We have developed the web-based software tool SPiCE for exploring
      sequence-based features of proteins in predefined classes. It offers data
      upload/download, sequence-based feature calculation, data visualization and
      protein classifier construction and testing in a single integrated, interactive
      environment. To illustrate its use, two example datasets are included showing the
      identification of differences in amino acid composition between proteins yielding
      low and high production levels in fungi and low and high expression levels in
      yeast, respectively. CONCLUSIONS: SPiCE is an easy-to-use online tool for
      extracting and exploring sequence-based features of sets of proteins, allowing
      non-experts to apply advanced classification techniques. The tool is available at
      http://helix.ewi.tudelft.nl/spice.

PMID- 24685259
TI  - Malignant peripheral nerve sheath tumours in the head and neck region:
      retrospective analysis of clinicopathological features and treatment outcomes.
AB  - Malignant peripheral nerve sheath tumours (MPNST) are rare soft tissue sarcomas.
      The aim of this study was to assess clinicopathological characteristics and
      prognostic factors in order to improve the treatment of such tumours in the head
      and neck region. We performed a retrospective analysis of head and neck MPNST
      patients in our hospital between 1996 and 2012. Clinical features and
      pathological findings of these cases (n=43) were summarized. In addition,
      prognostic variables were evaluated by univariate and multivariate analyses. The
      median age of the patients at presentation was 41 years. Surgery was the main
      treatment approach. Pertinent information regarding the presence of
      neurofibromatosis type 1 was found in 13 patients (30.2%). Two-thirds of these
      patients were admitted for a primary tumour (n=27, 62.8%), while one-third (n=16,
      37.2%) were treated for recurrent neoplasms. The overall survival rate was 46.5%.
      Multivariable analysis identified tumour size, surgical margins, and
      postoperative radiotherapy to be independent prognostic factors. MPNST of the
      head and neck is extremely difficult to manage. Surgery with postoperative
      radiation may be the optimum choice of treatment for primary head and neck MPNST.

PMID- 24685260
TI  - Control of cerebrospinal fluid otorrhea via C-arm-guided reduction of the
      zygomatic arch as a part of the temporal bone: interdisciplinary approach to an
      unusual craniomaxillofacial fracture.
AB  - Maxillofacial fractures are often associated with blunt head injuries, of which
      skull base trauma is a common component. However, most oral and maxillofacial
      surgeons do not provide definitive management of temporal bone fractures
      involving the skull base and their sequelae. Persistent cerebrospinal fluid (CSF)
      leakage that is refractory to conservative measures usually requires surgical
      closure to decrease the risk of meningitis. In general, reduction of the
      displaced fragment of the skull base in temporal bone fractures is not considered
      a priority. We describe an unusual case of craniomaxillofacial injury exhibiting
      CSF otorrhea because of a temporal bone fracture with a fragment that included
      the zygomatic arch. The persistent traumatic leakage was stopped after C-arm
      guided reduction of the depressed zygomatic arch. This technique facilitated
      minimal and only necessary manipulation, without overcorrection, thereby avoiding
      additional damage to the surrounding tissues. The present case illustrates the
      definitive contribution of therapeutic measures based on maxillofacial surgery as
      part of an interdisciplinary approach to the management of the complications of
      severe head injuries; more invasive neurosurgery was thus avoided. 

PMID- 24685261
TI  - Resection for oral tongue squamous cell carcinoma: a paradigm shift from
      conventional wide resection towards compartmental resection.

PMID- 24685262
TI  - Three-dimensional soft tissue change after paranasal augmentation with porous
      polyethylene.
AB  - The aim of this study was to investigate the effect of porous polyethylene (PPE)
      in paranasal augmentation on midfacial soft tissue architecture. This
      retrospective study recruited patients with midface retrusion and mandibular
      prognathism. Twenty adult patients who had undergone bilateral PPE augmentation
      (ready-made type, thickness 4.5mm, Medpor) to the piriform aperture and
      simultaneous mandibular setback surgery were included in this study. The soft
      tissue morphology and thickness of the midface were evaluated using three
      dimensional reformatted images from cone beam computed tomography done before and
      6 months after surgery. The soft tissue outline of the midface was augmented 1
      4mm. The average increase in soft tissue outline near the peri-alar region was
      3.1-3.4mm, which comprised 68-74% of the PPE thickness (P<0.01). The nasolabial
      angle and columellar inclination were increased significantly (2.2 degrees  and
      1.4 degrees , respectively; both P<0.05), whereas the nasal tip angle, nasal tip
      protrusion, columellar length, and bilateral nostril axis angle did not change.
      The alar base became wider on average by 2.2mm (P<0.01). The results showed that
      paranasal augmentation with PPE significantly increased the overlying soft tissue
      outline without influencing the nasal projection and could enhance paranasal
      aesthetics with minimal morbidity. 

PMID- 24685263
TI  - Sperm fertility and viability following 48h of refrigeration: evaluation of
      different extenders for the preservation of bull semen in liquid state.
AB  - Two experiments were conducted to compare the effectiveness of different
      extenders conventionally used for semen cryopreservation to maintain the
      viability and fertility of cooled bull semen. In Experiment 1, sperm samples
      obtained from 20 Nellore bulls were preserved at 5 degrees C for 48h using two
      extenders containing 20% of egg yolk [Tris (TRIS-R) and Botu-Bov((r)) (BB)] and
      another composed of 1% soy lecithin [Botu-Bov((r))-Lecithin (BB-L)] as
      substitutes for animal origin products. The samples were evaluated at 6, 24 and
      48h for plasma and acrosomal membrane integrity, quantification of thiobarbituric
      acid reactive substances (ng of TBARS/10(8) cells) and sperm motility parameters
      by computer-assisted semen analysis (CASA). In Experiment 2, pregnancy rate
      (P/AI) of 973 fixed-time artificially inseminated Nellore cows were compared when
      cows were inseminated with conventionally cryopreserved semen in TRIS-egg yolk
      glycerol (TRIS-C Control, n=253) or semen cooled for 48h in TRIS-R (n=233), BB
      (n=247) or BB-L (n=240). Although none of the extenders used was effective on
      maintaining total progressive motility and cellular integrity throughout the 48-h
      of the refrigeration period (P<0.01), BB-L conferred greater protection against
      oxidative stress (P<0.05) than egg yolk-based medias. The P/AI for semen samples
      preserved in TRIS-C, TRIS-R, BB and BB-L were 39.92(a), 25.32(b), 26.32(b) and
      33.33(ab), respectively. These results demonstrate that the three conventional
      extenders used for semen cryopreservation do not provide the protection required
      to maintain bull semen fertility under refrigeration for a 48-h period, resulting
      in reduced pregnancy rates. However, the use of lecithin-based medium instead of
      egg yolk results in greater protection against lipid peroxidation, producing P/AI
      results comparable to those obtained using frozen semen. 

PMID- 24685264
TI  - The in vitro and in vivo toxicity of graphene quantum dots.
AB  - Graphene quantum dots (GQD) generate intrinsic fluorescence, and improves aqueous
      stability of graphene oxide (GO) while maintaining wide chemical adaptability and
      high adsorption capacity. Despite GO's remarkable advantages in bio-imaging, bio
      sensing and other biomedical applications, its biosafety issues are still
      unclear. Here we report a detailed and systematic study on the in vitro and in
      vivo toxicity of GQD. The GQD sample was prepared through a facile oxidation
      approach and fully characterized by means of AFM, TEM, FTIR, XPS and elemental
      analysis. In vitro experiments showed that GQD exhibits very low cytotoxicity
      owing to its ultra-small size and high oxygen content. Then, the in vivo
      biodistribution experiment of GQD revealed no material accumulation in main
      organs of mice and fast clearance of GQD through kidney. In order to mimic clinic
      drug administration, mice were injected with GQD and GO (as comparison) multiple
      times for in vivo toxicity tests. We found that GQD showed no obvious influence
      on mice owing to its small size, while GO appeared toxic, even caused death to
      mice due to GO aggregation inside mice. In brief, GQD possesses no obvious in
      vitro and in vivo toxicity, even under multi-dosing situation.

PMID- 24685266
TI  - Anisotropic cell-to-cell spread of vaccinia virus on microgrooved substrate.
AB  - Cell-to-cell spread of virus is a comprehensive process with involvement of
      cellular actin cytoskeleton and substrate topography can affect the arrangement
      of cytoskeleton via contact guidance, yet interaction among virus, cytoskeleton
      and substrate topography is still unknown. To investigate the virus-cell
      substrate interaction, we designed a microgrooved poly(dimethyl siloxane) (PDMS)
      substrate for the study of vaccinia virus (VACV) cell-to-cell spread and the
      remodeling of cellular actin cytoskeleton in viral infection process.
      Interestingly, VACV-induced plaques on microgrooved substrate were elliptical
      instead of circular plaques on smooth substrate, suggesting an anisotropic cell
      to-cell spread of VACV. The spread rate was faster in the direction parallel to
      microgroove and slower in the direction perpendicular to microgroove than that on
      smooth substrate. Host cells cultured on microgrooved surface showed significant
      alignment and elongation in the axis parallel to microgrooves. Cell elongation is
      one reason for anisotropic spread but could not totally explain the phenomenon.
      Actin fibers in infected cells maintained alignment and VACV-induced actin tails
      tipped with virions were oriented along the direction parallel to microgroove.
      These results suggested that substrate topography can affect infected cells and
      these effects will guide the spread of virus via orientation of actin
      cytoskeleton. This work opens a window for understanding virus response to
      substrate topography, and has potential implications on revealing virus-cell
      substrate interactions in vivo.

PMID- 24685265
TI  - A solid-phase PEGylation strategy for protein therapeutics using a potent FGF21
      analog.
AB  - Fibroblast growth factor 21 (FGF21) is an endocrine-acting hormone that has the
      potential to treat metabolic diseases, such as type 2 diabetes and obesity.
      Development of FGF21 into a therapeutic has been hindered due to its low
      intrinsic bio-stability, propensity towards aggregation and its susceptibility to
      in vivo proteolytic degradation. In order to address these shortcomings, we've
      developed recombinant human FGF21 variants by strategically introducing cysteine
      residues via site-directed mutagenesis, and have also developed a solid-phase
      nickel affinity PEGylation strategy, whereby engineered, surface-exposed cysteine
      residues of immobilized proteins were used as a platform to efficiently and site
      selectively conjugate with PEG-maleimide. The engineered PEGylated FGF21
      conjugates retained its biological functions, as well as demonstrated an increase
      in half-life by over 211.3 min. By demonstrating the biological activity of the
      FGF21 analog as a prototype, we have also provided a "generalized" solid-phase
      approach to effectively increase serum half-life of protein therapeutics.

PMID- 24685267
TI  - Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer
      therapy.
AB  - The tumor tropism of mesenchymal stem cells (MSCs) makes them an excellent
      delivery vehicle used in anticancer therapy. However, the exact mechanisms of
      MSCs involved in tumor microenvironment are still not well defined. Molecular
      imaging technologies with the versatility in monitoring the therapeutic effects,
      as well as basic molecular and cellular processes in real time, offer tangible
      options to better guide MSCs mediated cancer therapy. In this study, an in situ
      breast cancer model was developed with MDA-MB-231 cells carrying a reporter
      system encoding a double fusion (DF) reporter gene consisting of firefly
      luciferase (Fluc) and enhanced green fluorescent protein (eGFP). In mice breast
      cancer model, we injected human umbilical cord-derived MSCs (hUC-MSCs) armed with
      a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine
      kinase (HSV-ttk), renilla luciferase (Rluc) and red fluorescent protein (RFP)
      into tumor on day 13, 18, 23 after MDA-MB-231 cells injection. Bioluminescence
      imaging of Fluc and Rluc provided the real time monitor of tumor cells and hUC
      MSCs simultaneously. We found that tumors were significantly inhibited by hUC
      MSCs administration, and this effect was enhanced by ganciclovir (GCV)
      application. To further demonstrate the effect of hUC-MSCs on tumor cells in
      vivo, we employed the near infrared (NIR) imaging and the results showed that hUC
      MSCs could inhibit tumor angiogenesis and increased apoptosis to a certain
      degree. In conclusion, hUC-MSCs can inhibit breast cancer progression by inducing
      tumor cell death and suppressing angiogenesis. Moreover, molecular imaging is an
      invaluable tool in tracking cell delivery and tumor response to hUC-MSCs
      therapies as well as cellular and molecular processes in tumor.

PMID- 24685268
TI  - [Authors' response to the Letter to the Editor "Acute mesenteric ischemia"].

PMID- 24685269
TI  - [Epiploic appendagitis: an uncommon cause of abdominal pain in primary care].

PMID- 24685270
TI  - Mitochondrial structure alteration in human prostate cancer cells upon initial
      interaction with a chemopreventive agent phenethyl isothiocyanate.
AB  - BACKGROUND: Phenethyl isothiocyanate (PEITC), present naturally in cruciferous
      vegetables, is a chemopreventive agent. It blocks initiation and post-initiation
      progression of carcinogenesis. Mechanism study in human prostate cancer cells
      revealed that PEITC is a dual inhibitor of aberrant DNA hypermethylation and
      histone deacetylases, reactivating silenced genes and regulating the androgen
      mediated growth of tumor cells. The identity of the cellular organelle that
      initially interacts with PEITC has not been fully described. METHODS: Human
      prostate cancer LNCaP cells were exposed to PEITC and the effects on cellular
      fine structure examined by transmission electron microscopic studies. Alteration
      of mitochondrial membrane potential and cytochrome c release were evaluated as
      early events of apoptosis, and the TUNEL method for quantifying apoptotic cells.
      Mitochondria were isolated for determining their protein expression. RESULTS:
      Ultrastructural analyses have revealed condensed mitochondria and a perturbed
      mitochondrial cristae structure, which assumed a rounded and dilated shape within
      4-hours of PEITC contact, and became more pronounced with longer PEITC exposure.
      They presented as the most prominent intracellular alterations in the early
      hours. Mitochondria structure alterations were demonstrated, for the first time,
      with the isothiocyanates. An increase in the number of smooth endoplasmic
      reticulum and vacuoles were also noted that is consistent with the presence of
      autophagy. Early events of apoptosis were detected, with cytochrome c released
      along with the appearance of mitochondrial alteration. Mitochondrial membrane
      potential was disrupted within 18 hours of PEITC exposure, preceding the
      appearance of apoptotic cells with DNA strand breaks. In parallel, the expression
      of the mitochondrial class III beta-tubulin in the outer membrane, which
      associates with the permeability transition pore, was significantly reduced as
      examined with isolated mitochondria. CONCLUSION: Mitochondria may represent the
      organelle target of the isothiocyanates, indicating that the isothiocyanates may
      be mitochondria-interacting agents to inhibit carcinogenesis.

PMID- 24685271
TI  - The Effective Field Theory approach towards membrane-mediated interactions
      between particles.
AB  - Fluid lipid membranes can mediate forces between particles bound to them: A local
      deformation of the surface geometry created by some object spreads to distant
      regions, where other objects can respond to it. The physical characteristics of
      these geometric interactions, and how they are affected by thermal fluctuations,
      are well described by the simple continuum curvature-elastic Hamiltonian proposed
      40 years ago by Wolfgang Helfrich. Unfortunately, while the underlying principles
      are conceptually straightforward, the corresponding calculations are not-largely
      because one must enforce boundary conditions for finite-sized objects. This
      challenge has inspired several heuristic approaches for expressing the problem in
      a point particle language. While streamlining the calculations of leading order
      results and enabling predictions for higher order corrections, the ad hoc nature
      of the reformulation leaves its domain of validity unclear. In contrast, the
      framework of Effective Field Theory (EFT) provides a systematic way to construct
      a completely equivalent point particle description. In this review we present a
      detailed account for how this is accomplished. In particular, we use a familiar
      example from electrostatics as an analogy to motivate the key steps needed to
      construct an EFT, most notably capturing finite size information in point-like
      "polarizabilities," and determining their value through a suitable "matching
      procedure." The interaction (free) energy then emerges as a systematic cumulant
      expansion, for which powerful diagrammatic techniques exist, which we also
      briefly revisit. We then apply this formalism to derive series expansions for
      interactions between flat and curved particle pairs, multibody interactions, as
      well as corrections to all these interactions due to thermal fluctuations.

PMID- 24685272
TI  - Phospholipid-based nonlamellar mesophases for delivery systems: bridging the gap
      between empirical and rational design.
AB  - Phospholipids are ubiquitous cell membrane components and relatively well
      accepted ingredients due to their natural origin. Phosphatidylcholine (PC) in
      particular offers a promising alternative to monoglycerides for lyotropic liquid
      crystalline (LLC) delivery system applications in the food, cosmetics and
      pharmaceutical industries, provided its strong tendency to form zero-mean
      curvature lamellar mesophases in water can be overcome. Higher negative
      curvatures are usually reached through the addition of a third lipid component,
      forming a ternary diagram phospholipid/water/oil. The initial part of this work
      summarizes the potential advantages and the challenges of phospholipid-based
      delivery system applications. In the next part, various ternary PC/water/oil
      systems are discussed, with a special emphasis on the PC/water/cyclohexane and
      PC/water/alpha-tocopherol systems. We report that R-(+)-limonene has a
      quantitatively similar effect as cyclohexane. The last part is devoted to the
      theoretical interpretation of the observed phase behaviors. A fruitful parallel
      is drawn with PC polymer-like reverse micelles, leading to a thermodynamic
      description in terms of interfacial bending energy. Investigations at the
      molecular level are reviewed to help in bridging the empirical and theoretical
      approaches. Predictive rules are finally derived from this wide-ranging overview,
      thereby opening the way to a future rational design of PC-based LLC delivery
      systems. 

PMID- 24685273
TI  - Molecular phylogeny of Triatomini (Hemiptera: Reduviidae: Triatominae).
AB  - BACKGROUND: The Triatomini and Rhodniini (Hemiptera: Reduviidae) tribes include
      the most diverse Chagas disease vectors; however, the phylogenetic relationships
      within the tribes remain obscure. This study provides the most comprehensive
      phylogeny of Triatomini reported to date. METHODS: The relationships between all
      of the Triatomini genera and representatives of the three Rhodniini species
      groups were examined in a novel molecular phylogenetic analysis based on the
      following six molecular markers: the mitochondrial 16S; Cytochrome Oxidase I and
      II (COI and COII) and Cytochrome B (Cyt B); and the nuclear 18S and 28S. RESULTS:
      Our results show that the Rhodnius prolixus and R. pictipes groups are more
      closely related to each other than to the R. pallescens group. For Triatomini, we
      demonstrate that the large complexes within the paraphyletic Triatoma genus are
      closely associated with their geographical distribution. Additionally, we observe
      that the divergence within the spinolai and flavida complex clades are higher
      than in the other Triatoma complexes. CONCLUSIONS: We propose that the spinolai
      and flavida complexes should be ranked under the genera Mepraia and Nesotriatoma.
      Finally, we conclude that a thorough morphological investigation of the
      paraphyletic genera Triatoma and Panstrongylus is required to accurately assign
      queries to natural genera.

PMID- 24685274
TI  - Arsenic trioxide inhibits Hedgehog, Notch and stem cell properties in
      glioblastoma neurospheres.
AB  - BACKGROUND: Notch and Hedgehog signaling have been implicated in the pathogenesis
      and stem-like characteristics of glioblastomas, and inhibitors of the pathways
      have been suggested as new therapies for these aggressive tumors. It has also
      been reported that targeting both pathways simultaneously can be advantageous in
      treating glioblastoma neurospheres, but this is difficult to achieve in vivo
      using multiple agents. Since arsenic trioxide has been shown to inhibit both
      Notch and Hedgehog in some solid tumors, we examined its effects on these
      pathways and on stem cell phenotype in glioblastoma. RESULTS: We found that
      arsenic trioxide suppresses proliferation and promotes apoptosis in three stem
      like glioblastoma neurospheres lines, while inhibiting Notch and Hedgehog target
      genes. Importantly, arsenic trioxide markedly reduced clonogenic capacity of the
      tumor neurospheres, and the stem-like CD133-positive fraction was also diminished
      along with expression of the stem cell markers SOX2 and CD133. CONCLUSIONS: Our
      results suggest that arsenic trioxide may be effective in targeting stem-like
      glioblastoma cells in patients by inhibiting Notch and Hedgehog activity.

PMID- 24685275
TI  - Invited commentary on Australian fetal alcohol spectrum disorder diagnostic
      guidelines.
AB  - The publication of Australian fetal alcohol spectrum disorder (FASD) diagnostic
      guidelines marks an important step forward in Australia's efforts to prevent
      FASD. But do we need yet another set of FASD guidelines? At the 5th International
      FASD Conference, the ever growing number of FASD diagnostic guidelines was
      identified as a core area of concern by leaders in FASD worldwide. All agreed we
      need to strive to adopt a single set of guidelines. It is essential that FASD
      diagnosis advance to incorporate new knowledge and technology. But to date, the
      field of FASD has seen multiple sets of guidelines published that do not address
      the important question-How is the performance of these new guidelines superior to
      the performance of existing guidelines to warrant/justify their introduction into
      the medical literature?The Australian guidelines include FAS, PFAS and
      Neurodevelopmental Disorder-Alcohol Exposed (ND-AE). This latter group includes
      individuals with severe CNS abnormalities without the physical features of FAS.
      This is the group the 4-Digit-Code calls Static-Encephalopathy-Alcohol-Exposed
      (SE-AE). The criteria for FAS, PFAS, and ND-AE (or what the 4-Digit-Code calls SE
      AE) are identical between the Australian and 4-Digit-Code guidelines with the
      exception of one very small, but very consequential difference in facial criteria
      for PFAS. The 4-Digit-Code requires a Rank 3 FAS facial phenotype for PFAS (J
      Popul Ther Clin Pharmacol20(3):e416-e467, 2013); the Australian guidelines relax
      the criteria to include the Rank 2 FAS facial phenotype. This relaxation of the
      criteria renders the facial phenotype NOT specific to prenatal alcohol exposure
      as confirmed in published empirical studies. If the facial phenotype is not
      specific to (caused only by) prenatal alcohol exposure one can no longer validly
      call the outcome PFAS. When one makes a diagnosis of FAS (full or partial), one
      is stating explicitly that the individual has a syndrome caused by prenatal
      alcohol exposure. One is also stating explicitly that the biological mother drank
      alcohol during pregnancy and, as a result, harmed her child. These are bold
      conclusions to draw and are not without medical, ethical, and even legal
      consequences. So the question remains-Why go against the published empirical
      evidence and relax the PFAS facial criteria into the normal range? 

PMID- 24685277
TI  - Effects of fingolimod in relapsing-remitting multiple sclerosis.

PMID- 24685276
TI  - Safety and efficacy of fingolimod in patients with relapsing-remitting multiple
      sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3
      trial.
AB  - BACKGROUND: Fingolimod has shown reductions in clinical and MRI disease activity
      in patients with relapsing-remitting multiple sclerosis. We further assessed the
      efficacy and safety of fingolimod in such patients. METHODS: We did this placebo
      controlled, double-blind phase 3 study predominantly in the USA (101 of 117
      centres). Using a computer-generated sequence, we randomly allocated eligible
      patients-those aged 18-55 years with relapsing-remitting multiple sclerosis-to
      receive fingolimod 0.5 mg, fingolimod 1.25 mg, or placebo orally once daily
      (1:1:1; stratified by study centre). On Nov 12, 2009, all patients assigned to
      fingolimod 1.25 mg were switched to the 0.5 mg dose in a blinded manner after a
      review of data from other phase 3 trials and recommendation from the data and
      safety monitoring board, but were analysed as being in the 1.25 mg group in the
      primary outcome analysis. Our primary endpoint was annualised relapse rate at
      month 24, analysed by intention to treat. Secondary endpoints included percentage
      brain volume change (PBVC) from baseline and time-to-disability-progression
      confirmed at 3 months. This trial is registered with ClinicalTrilals.gov, number
      NCT00355134. FINDINGS: Between June 30, 2006, and March 4, 2009, we enrolled and
      randomly allocated 1083 patients: 370 to fingolimod 1.25 mg, 358 to fingolimod
      0.5 mg, and 355 to placebo. Mean annualised relapse rate was 0.40 (95% CI 0.34
      0.48) in patients given placebo and 0.21 (0.17-0.25) in patients given fingolimod
      0.5 mg: rate ratio 0.52 (95% CI 0.40-0.66; p<0.0001), corresponding to a
      reduction of 48% with fingolimod 0.5 mg versus placebo. Mean PBVC was -0.86 (SD
      1.22) for fingolimod 0.5 mg versus -1.28 (1.50) for placebo (treatment difference
      -0.41, 95% CI -0.62 to -0.20; p=0.0002). We recorded no statistically significant
      between-group difference in confirmed disability progression (hazard rate 0.83
      with fingolimod 0.5 mg vs placebo; 95% CI 0.61-1.12; p=0.227). Fingolimod 0.5 mg
      caused more of the following adverse events versus placebo: lymphopenia (27 [8%]
      patients vs 0 patients), increased alanine aminotransferase (29 [8%] vs six
      [2%]), herpes zoster infection (nine [3%] vs three [1%]), hypertension (32 [9%]
      vs 11 [3%]), first-dose bradycardia (five [1%] vs one [<0.5%]), and first-degree
      atrioventricular block (17 [5%] vs seven [2%]). 53 (15%) of 358 patients given
      fingolimod 0.5 mg and 45 (13%) of 355 patients given placebo had serious adverse
      events over 24 months, which included basal-cell carcinoma (ten [3%] patients vs
      two [1%] patients), macular oedema (three [1%] vs two [1%]), infections (11 [3%]
      vs four [1%]), and neoplasms (13 [4%] vs eight [2%]). INTERPRETATION: Our
      findings expand knowledge of the safety profile of fingolimod and strengthen
      evidence for its beneficial effects on relapse rates in patients with relapsing
      remitting multiple sclerosis. We saw no effect of fingolimod on disability
      progression. Our findings substantiate the beneficial profile of fingolimod as a
      disease-modifying agent in the management of patients with relapsing-remitting
      multiple sclerosis. FUNDING: Novartis Pharma AG.

PMID- 24685278
TI  - Neuropsychiatric outcomes of stroke.
AB  - The most common neuropsychiatric outcomes of stroke are depression, anxiety,
      fatigue, and apathy, which each occur in at least 30% of patients and have
      substantial overlap of prevalence and symptoms. Emotional lability, personality
      changes, psychosis, and mania are less common but equally distressing symptoms
      that are also challenging to manage. The cause of these syndromes is not known,
      and there is no clear relation to location of brain lesion. There are important
      gaps in knowledge about how to manage these disorders, even for depression, which
      is the most studied syndrome. Further research is needed to identify causes and
      interventions to prevent and treat these disorders. 

PMID- 24685279
TI  - A case of stings in humans caused by Sclerodermus sp. in Italy.
AB  - In the last years, stings of Sclerodermus species in humans have been
      sporadically reported in Italy. In order to draw attention to these bethylid
      wasps of medical importance, we report the case of documented Sclerodermus sp.
      stings on the dorsum, abdomen, arms, and thighs of a 40-year-old man and his
      wife. The sting sites developed raised red itchy rash. The source of
      environmental contamination was identified in a worm-eaten sofa purchased from a
      used furniture dealer and placed in the living room about a month and half
      earlier. The lesions on the man and his wife rapidly healed within 3 to 4 days
      once they left the house and treatment for the lesions was instituted.
      Physicians, dermatologists, medical and public health entomologists, as well as
      specific categories of workers should be aware of the risk of exposure to
      Sclerodermus stings. 

PMID- 24685280
TI  - Correlation between antibiotic consumption and carbapenem-resistant Acinetobacter
      baumannii causing health care-associated infections at a hospital from 2005 to
      2010.
AB  - BACKGROUND/PURPOSE: This study investigated the correlation between antibiotic
      consumption and the incidence of health care-associated infections (HCAIs) caused
      by imipenem-resistant Acinetobacter baumannii (IRAB) at a hospital in Taiwan from
      2005 to 2010. METHODS: Data on annual consumption (defined daily dose per 1000
      patient-days) of extended-spectrum cephalosporins, beta-lactam-beta-lactamase
      inhibitor combinations, carbapenems, aminoglycosides, and fluoroquinolones from
      2005 to 2010 were analyzed. Yearly aggregated data on the number of nonduplicate
      clinical IRAB isolates causing HCAI were collected. The incidence rates of HCAI
      caused by IRAB were defined as the number of patients infected with IRAB per 1000
      inpatient-days. RESULTS: The trend of total consumption (defined daily dose per
      1000 patient-days) of extended-spectrum cephalosporins, carbapenems, and
      fluoroquinolones was significantly increased, but the use of aminoglycosides
      decreased during 2005 to 2010. During the same period, the incidence of HCAI
      caused by IRAB gradually increased. The consumptions of carbapenems and
      fluoroquinolones were positively correlated with the incidence of HCAI caused by
      IRAB. There was no significant association between the use of extended-spectrum
      cephalosporins, beta-lactam-beta-lactamase inhibitor combinations, and
      aminoglycosides and the incidence of HCAI caused by IRAB. CONCLUSION: The
      increasing use of carbapenems and fluoroquinolones was associated with the
      increasing incidence of HCAI caused by IRAB.

PMID- 24685282
TI  - Effect of oxygen on multidrug resistance in term human placenta.
AB  - INTRODUCTION: The placenta contains efflux transporters, including P-glycoprotein
      (P-gp) and breast cancer resistance protein (BCRP), that limit the passage of
      xenobiotics, certain hormones and nutrients from the maternal to the fetal
      circulation. The expression of these transporters changes with gestational age,
      yet the mechanisms involved remain unknown. However, the changes in P-gp and BCRP
      transporter expression coincide with those of oxygen tension in the placenta, and
      oxygen tension has been shown to modulate P-gp and BCRP expression in other
      tissues. The objective of this study was to investigate the effects of oxygen
      tension on P-gp and BCRP expression in the term human placenta. METHODS:
      Following equilibration in culture (96 h), term placental explants (n = 7) were
      cultured in 3% or 20% oxygen for 24 and 48 h. Culture medium was collected every
      24 h to measure lactate dehydrogenase (LDH; explant viability) and human
      chorionic gonadotropin (hCG; syncytiotrophoblast function). P-gp (encoded by
      ABCB1) and BCRP (encoded by ABCG2) protein and mRNA, as well as VEGFA mRNA were
      measured using western blot and qRT-PCR. P-gp localization was determined using
      immunofluorescence. RESULTS: Oxygen tension had a significant effect on P-gp
      expression, with ABCB1/P-gp mRNA and protein levels increased in the hypoxic
      condition (3% O2) after 48 h (p < 0.05). VEGFA mRNA was elevated by hypoxia at
      both 24 and 48 h (p < 0.05). In contrast, placental ABCG2/BCRP mRNA and protein
      expression were stable with changes in oxygen tension. We identified profound
      differences in the glycosylation of P-gp between cultured and non-cultured
      placental tissue, with cultured explants expressing deglycosylated P-gp.
      CONCLUSIONS: These findings demonstrate that, at term, the expression of
      placental P-gp, is regulated by oxygen tension. This suggests that changes in
      oxygenation of the placenta in the third trimester may alter levels of placental
      P-gp, and in doing so alter fetal exposure to P-gp substrates, including
      xenobiotics and certain hormones.

PMID- 24685283
TI  - Trends of fruit and vegetable availability in neighbourhoods in Albany, NY, USA,
      2003-2012.
AB  - OBJECTIVE: To investigate a 9-year trend of fresh fruit and vegetable
      availability and factors associated with the net availability change in two
      contrasting neighbourhoods. DESIGN: Longitudinal design. Data were collected in
      2003, 2009 and 2012 through in-store observations. Fresh fruit and vegetable
      availability was presented by weight-adjusted counts of stores having designated
      varieties per 10 000 population. SETTING: A low-income minority neighbourhood and
      an adjacent middle-income racially mixed neighbourhood in Albany, NY, USA. These
      neighbourhoods became sites of fresh produce interventions after baseline data
      were collected. SUBJECTS: A total of 111, 128 and 146 eligible food stores in
      respective years. RESULTS: Fresh fruit availability (two or more varieties)
      increased in both neighbourhoods. Inventory expansion of existing stores and the
      convenience store intervention contributed to the significant increase (P for
      trend=0.04) of fresh fruit availability in the minority neighbourhood. Although
      not statistically significant (P>0.05), the availability of two or more dark
      coloured fresh vegetables also increased in the mixed neighbourhood, but declined
      slightly in the minority neighbourhood. The secular (non-intervention) fresh
      vegetable availability rate ratio by neighbourhood reached 3.0 in 2012 (P<0.01).
      The net decline of fresh vegetable availability in the minority neighbourhood was
      primarily attributed to inventory reduction of existing stores. CONCLUSIONS:
      Longitudinal observations revealed narrowed neighbourhood disparities of fresh
      fruit availability and widened gaps of fresh vegetable availability. Inventory
      shifts of existing stores impacted the net availability change more profoundly
      than store opening or closing in the minority neighbourhood. Findings support
      increasing the programme capacity of the convenience store intervention to
      address the fresh vegetable disparity.

PMID- 24685284
TI  - Eradication of a chronic wound and driveline infection after redo-LVAD
      implantation.
AB  - A 48 year old patient with dilated cardiomyopathy and chronic acne inversa
      underwent implantation of a LVAD system (Heartmate II, Thoratec, USA) March 2011.
      During 2011 and 2012 the patient was repeatedly readmitted for treatment of
      driveline infection with MRSA. Colonization was controlled with Linezolid and
      Rifampicin however reoccurred after discontinuation. In August 2012 the LVAD
      system was exchanged due to pump dysfunction (HVAD, HeartWare Inc., USA).
      Postoperatively, the patient presented with ascites which secreted through the
      driveline exit. Consequently, the abdominal wall was surgically corrected to
      prevent exit of peritoneal fluid through the driveline, and the patient was
      discharged with sterile wound swabs. However 6 weeks after discharge the
      driveline exit wound started secreting pus showing abundant growth of multi
      resistant staphylococcus aureus (MRSA). With clinical signs of increasing liver
      failure with regular need for paracentesis, and clinical signs of local
      infection, a CT scan of the abdomen was performed revealing an enrichment of
      contrast medium along the driveline and an abscess-like formation on the
      abdominal wall. Patient was admitted receiving regular dose Daptomycin and
      Rifampicin. The latter was discontinued after ten days. The abscess, surrounding
      driveline exit and abdominal wall cavity was excised and vacuum treatment
      initiated. Total duration of Daptomycin therapy was 3 weeks. While first week
      skin and wound swabs were still positive for MRSA, all samples were sterile after
      the second week. Inflammation was monitored by leucocyte count and IL6. The
      secretion of pus along the driveline ceased, the wound cavity was closed
      subsequently. After discharge and stop of antibiotics skin and driveline swabs
      remained negative for MRSA (10 weeks).

PMID- 24685285
TI  - A schizophrenia risk gene, ZNF804A, is associated with brain white matter
      microstructure.
AB  - Genome-wide association studies have provided strong evidence for association of
      the SNP rs1344706 in the ZNF804A gene with schizophrenia and bipolar disorder.
      Neuroimaging studies have suggested that variation at rs1344706 may be associated
      with neural endophenotypes such as white matter volumes and densities. However,
      analyses of white matter microstructure using diffusion tensor imaging (DTI) have
      produced conflicting results. We examined the association between rs1344706 and
      white matter microstructure in 107 healthy individuals using tract-based spatial
      statistics (TBSS). TBSS analysis showed significant association between the risk
      allele and lower fractional anisotropy in the corpus callosum, left forceps
      minor, and right parietal white matter (p<.05; FWE corrected). Post-hoc analyses
      indicated that this association was largely driven by alterations in radial
      diffusivity, consistent with an effect of genotype on myelination. In light of
      the strong DTI evidence for white matter microstructural abnormalities in
      schizophrenia, the current results implicate a potential mechanism for
      schizophrenia risk formation by ZNF804A rs1344706 genotype. 

PMID- 24685287
TI  - Towards successful user interaction with systems: focusing on user-derived
      gestures for smart home systems.
AB  - Various studies that derived gesture commands from users have used the frequency
      ratio to select popular gestures among the users. However, the users select only
      one gesture from a limited number of gestures that they could imagine during an
      experiment, and thus, the selected gesture may not always be the best gesture.
      Therefore, two experiments including the same participants were conducted to
      identify whether the participants maintain their own gestures after observing
      other gestures. As a result, 66% of the top gestures were different between the
      two experiments. Thus, to verify the changed gestures between the two
      experiments, a third experiment including another set of participants was
      conducted, which showed that the selected gestures were similar to those from the
      second experiment. This finding implies that the method of using the frequency in
      the first step does not necessarily guarantee the popularity of the gestures. 

PMID- 24685286
TI  - Chloroquine efficacy studies confirm drug susceptibility of Plasmodium vivax in
      Chennai, India.
AB  - BACKGROUND: Assessing the Plasmodium vivax burden in India is complicated by the
      potential threat of an emerging chloroquine (CQ) resistant parasite population
      from neighbouring countries in Southeast Asia. Chennai, the capital of Tamil Nadu
      and an urban setting for P. vivax in southern India, was selected as a sentinel
      site for investigating CQ efficacy and sensitivity in vivax malaria. METHODS: CQ
      efficacy was evaluated with a 28-day in vivo therapeutic study, while CQ
      sensitivity was measured with an in vitro drug susceptibility assay. In both
      studies, isolates also underwent molecular genotyping to investigate correlations
      between parasite diversity and drug susceptibility to CQ. Molecular genotyping
      included sequencing a 604 base pair (bp) fragment of the P. vivax multidrug
      resistant gene-1 (Pvmdr1) for single nucleotide polymorphisms (SNPs) and also the
      amplification of eight microsatellite (MS) loci located across the genome on
      eight different chromosomes. RESULTS: In the 28-day in vivo study (N=125), all
      subjects were aparasitaemic by Day 14. Passive case surveillance continuing
      beyond Day 28 in 22 subjects exposed 17 recurrent infections, which ranged from
      44 to 148 days post-enrollment. Pvmdr1 sequencing of these recurrent infections
      revealed that 93.3% had identical mutant haplotypes (958M/Y976/1076L) to their
      baseline Day 0 infection. MS genotyping further revealed that nine infection
      pairs were related with >= 75% haplotype similarity (same allele at six or more
      loci). To test the impact of this mutation on CQ efficacy, an in vitro drug assay
      (N=68) was performed. No correlation between IC50 values and the percentage of
      ring-stage parasites prior to culture was observed (r(sadj): -0.00063, p =
      0.3307) and the distribution of alleles among the Pvmdr1 SNPs and MS haplotypes
      showed no significant associations with IC50 values. CONCLUSIONS: Plasmodium
      vivax was found to be susceptible to CQ drug treatment in both the in vivo
      therapeutic drug study and the in vitro drug assay. Though the mutant 1076 L of
      Pvmdr1 was found in a majority of isolates tested, this single mutation did not
      associate with CQ resistance. MS haplotypes revealed strong heterogeneity in this
      population, indicating a low probability of reinfection with highly related
      haplotypes.

PMID- 24685288
TI  - Health benefits of hormonal contraception.

PMID- 24685289
TI  - A review of vitamin D and Parkinson's disease.
AB  - The role of vitamin D in bone health has been known for over a century. More
      recent research has suggested that vitamin D may play a role in the muscular,
      immune, endocrine, and central nervous systems. Animal research suggests that
      vitamin D may have some protective effects against toxic insults that are known
      to damage dopamine cells, the primary cells to degenerate in PD. Persons with PD
      tend to have lower vitamin D levels than persons of similar ages without PD.
      Vitamin D levels are generally associated with bone mineral density (BMD) in
      persons with PD, but simply giving vitamin D does not appear to improve BMD.
      Results of genetic studies examining polymorphism of the vitamin D receptor and
      PD risk, severity, or age at onset have shown variable results, with FokI CC
      seeming to possibly carry some increased risk of PD. Amount of sun exposure and
      vitamin D levels in earlier life may influence the risk of developing PD. Cross
      sectional research suggests a relationship between vitamin D levels and severity
      of PD symptoms. A single intervention study did show some improvement in PD with
      vitamin D supplementation. Vitamin D may have effects on PD symptoms and perhaps
      even on the risk of disease development or disease progression. More well
      designed intervention studies are needed to confirm the effect of vitamin D on PD
      symptoms. Human neuroprotection studies are needed, but probably not feasible
      until better biomarkers are established.

PMID- 24685290
TI  - Effects of mild and global cognitive impairment on the prevalence of fear of
      falling in community-dwelling older adults.
AB  - OBJECTIVES: Few studies have reported the relationship between fear of falling
      (FoF) and mild and global cognitive impairment in community-dwelling older
      adults. We aimed to determine whether the status of cognitive impairment affects
      the prevalence of FoF in community-dwelling older adults. STUDY DESIGN: Cross
      sectional study among 4474 community-dwelling older adults who participated in
      the Obu Study of Health Promotion for the Elderly. MAIN OUTCOME MEASURES:
      Participants underwent cognitive tests and were divided into three groups:
      cognitive healthy, mild cognitive impairment (MCI), and global cognitive
      impairment (GCI). FoF and related variables, such as fall history, physical
      function, and depression, were also investigated. RESULTS: The prevalence of FoF
      was significantly different by group (p<0.001; healthy: 43.6%, MCI: 50.6%, GCI:
      40.6%). Logistic regression analysis showed that GCI (odds ratio=0.63; 95%
      confidence interval=0.526-0.76) was independently associated with FoF, after
      controlling for confounding factors. Older adults with GCI showed the lowest
      prevalence of FoF, although they had the lowest physical function comparing with
      the other groups (p<0.001). CONCLUSION: MCI and GCI in community-dwelling older
      adults affect the prevalence of FoF in a completely different manner. Further
      study is required to determine whether insensitivity to FoF with GCI increases
      the risk of falling in older adults.

PMID- 24685291
TI  - Neuroimaging in dementia.
AB  - Over the last few years, advances in neuroimaging have generated biomarkers,
      which increase diagnostic certainty, provide valuable information about
      prognosis, and suggest a particular pathology underlying the clinical dementia
      syndrome. We aim to review the evidence for use of already established imaging
      modalities, along with selected techniques that have a great potential to guide
      clinical decisions in the future. We discuss structural, functional and molecular
      imaging, focusing on the most common dementias: Alzheimer's disease, fronto
      temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we
      stress the importance of conducting research using representative cohorts and in
      a naturalistic set up, in order to build a strong evidence base for translating
      imaging methods for a National Health Service. If we assess a broad range of
      patients referred to memory clinic with a variety of imaging modalities, we will
      make a step towards accumulating robust evidence and ultimately closing the gap
      between the dramatic advances in neurosciences and meaningful clinical
      applications for the maximum benefit of our patients. 

PMID- 24685292
TI  - Q&A: What are strigolactones and why are they important to plants and soil
      microbes?
AB  - What are strigolactones? Strigolactones are signaling compounds made by plants.
      They have two main functions: first, as endogenous hormones to control plant
      development, and second as components of root exudates to promote symbiotic
      interactions between plants and soil microbes. Some plants that are parasitic on
      other plants have established a third function, which is to stimulate germination
      of their seeds when in close proximity to the roots of a suitable host plant. It
      is this third function that led to the original discovery and naming of
      strigolactones. 

PMID- 24685293
TI  - Distinct origins of dura mater graft-associated Creutzfeldt-Jakob disease: past
      and future problems.
AB  - Dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) can be divided into
      two subgroups that exhibit distinct clinical and neuropathological features, with
      the majority represented by a non-plaque-type of dCJD (np-dCJD) and the minority
      by a plaque-type of dCJD (p-dCJD). The two distinct phenotypes of dCJD had been
      considered to be unrelated to the genotype (methionine, M or valine, V) at
      polymorphic codon 129 of the PRNP gene or type (type 1 or type 2) of abnormal
      isoform of prion protein (PrPSc) in the brain, while these are major determinants
      of clinicopathological phenotypes of sporadic CJD (sCJD). The reason for the
      existence of two distinct subgroups in dCJD had remained elusive. Recent progress
      in research of the pathogenesis of dCJD has revealed that two distinct subgroups
      of dCJD are caused by infection with different PrPSc strains from sCJD, i.e., np
      dCJD caused by infection with sCJD-MM1/MV1, and p-dCJD caused by infection with
      sCJD-VV2 or -MV2. These studies have also revealed previously unrecognized
      problems as follows: (i) the numbers of p-dCJD patients may increase in the
      future, (ii) the potential risks of secondary infection from dCJD, particularly
      from p-dCJD, may be considerable, and (iii) the effectiveness of the current
      PrPSc decontamination procedures against the PrPSc from p-dCJD is uncertain. To
      prevent secondary infection from p-dCJD, the establishment of effective
      decontamination procedures is an urgent issue. In this review, we summarize the
      past and future problems surrounding dCJD. 

PMID- 24685295
TI  - Adjuvant induced autoimmune/inflammatory syndrome presenting as joint and lung
      manifestations.
AB  - A 59 year-old female with a history of injection of an oily material in the
      buttocks 11 years ago. She developed symmetric aditive polyarthritis as well as
      superior and inferior airways involvement. There was no evidence of
      granulomatosis with polyangiitis (Wegener). She had several serum autoantibodies
      and a skin biopsy showed a foreign body granuloma. The diagnosis of adjuvant
      induced autoimmune/inflammatory syndrome was made. The pulmonary involvement was
      an atypical manifestation at the onset of disease. 

PMID- 24685296
TI  - Role of transforming growth factor-beta (TGF) beta in the physiopathology of
      rheumatoid arthritis.
AB  - Transforming growth factor-beta (TGF-beta) is a cytokine with pleiotropic
      functions in hematopoiesis, angiogenesis, cell proliferation, differentiation,
      migration and apoptosis. Although its role in rheumatoid arthritis is not well
      defined, TGF-beta activation leads to functional immunomodulatory effects
      according to environmental conditions. The function of TGF-beta in the
      development of arthritis in murine models has been extensively studied with
      controversial results. Recent findings point to a non-relevant role for TGF-beta
      in a mice model of collagen-induced arthritis. The study of TGF-beta on T-cell
      responses has shown controversial results as an inhibitor or promoter of the
      inflammatory response. This paper presents a review of the role of TGF-beta in
      animal models of arthritis. 

PMID- 24685294
TI  - Complete mitochondrial genomes of the 'intermediate form' of Fasciola and
      Fasciola gigantica, and their comparison with F. hepatica.
AB  - BACKGROUND: Fascioliasis is an important and neglected disease of humans and
      other mammals, caused by trematodes of the genus Fasciola. Fasciola hepatica and
      F. gigantica are valid species that infect humans and animals, but the specific
      status of Fasciola sp. ('intermediate form') is unclear. METHODS: Single
      specimens inferred to represent Fasciola sp. ('intermediate form'; Heilongjiang)
      and F. gigantica (Guangxi) from China were genetically identified and
      characterized using PCR-based sequencing of the first and second internal
      transcribed spacer regions of nuclear ribosomal DNA. The complete mitochondrial
      (mt) genomes of these representative specimens were then sequenced. The
      relationships of these specimens with selected members of the Trematoda were
      assessed by phylogenetic analysis of concatenated amino acid sequence datasets by
      Bayesian inference (BI). RESULTS: The complete mt genomes of representatives of
      Fasciola sp. and F. gigantica were 14,453 bp and 14,478 bp in size, respectively.
      Both mt genomes contain 12 protein-coding genes, 22 transfer RNA genes and two
      ribosomal RNA genes, but lack an atp8 gene. All protein-coding genes are
      transcribed in the same direction, and the gene order in both mt genomes is the
      same as that published for F. hepatica. Phylogenetic analysis of the concatenated
      amino acid sequence data for all 12 protein-coding genes showed that the specimen
      of Fasciola sp. was more closely related to F. gigantica than to F. hepatica.
      CONCLUSIONS: The mt genomes characterized here provide a rich source of markers,
      which can be used in combination with nuclear markers and imaging techniques, for
      future comparative studies of the biology of Fasciola sp. from China and other
      countries.

PMID- 24685297
TI  - Tai chi as a potentially effective treatment for neck pain.

PMID- 24685298
TI  - Needlestick and sharps injuries among dental healthcare workers at a university
      hospital.
AB  - BACKGROUND/PURPOSE: Needlestick/sharps injuries (NSI) are a major occupational
      hazard among healthcare workers. Since needles and sharps are commonly used
      during dental procedures, workers in the dental profession are especially prone
      to sharps-related injuries. In this study, NSI among workers in the dental
      department of National Taiwan University Hospital (NTUH) were analyzed to find
      out the risk factors associated with NSI. METHODS: NSI cases reported by the
      Department of Dentistry to NTUH from 2009 to 2011 were collected. Correlations
      between NSI and parameters related to the events were analyzed. RESULTS: A total
      of 56 NSI events including 31 occurring during surgical treatment and 25
      occurring during cleanup procedure were reported. The annual incidence of NSI was
      8.19% among all dental workers. NSI incidences per person-year were 21.28% for
      interns, 7.50% for residents, 6.77% for nursing staffs, 3.33% for clerks, and
      0.85% for attending doctors (P < 0.001, chi-square test). NSI events occurred
      more frequently in the 3-month period from July to September (20 cases), on
      Wednesday (18 cases) or Friday (14 cases), and at the hours from 11:00 to 14:00
      and after 16:00 (39 cases). Dental injection needle (19 cases) was the most
      common instrument involved in NSI and 9 of these 19 needle injuries occurred
      during need removal. CONCLUSION: NSI events tend to occur in dental personnel
      (interns) with lesser clinical skill and experience, in the period (from July to
      September) when new interns and residents join the clinic, on the working days in
      the middle (Wednesday) and end (Friday) of the week, and at the hours close to
      lunch break (11:00 to 14:00) and getting off duty (after 16:00). In addition,
      establishment of standard operating procedure for injection needle removal is
      necessary, because one-third of NSI are needle-related.

PMID- 24685299
TI  - Tests of data quality, scaling assumptions, reliability, and construct validity
      of the SF-36 health survey in people who abuse heroin.
AB  - BACKGROUND/PURPOSE: Health-related quality of life (HRQOL) is considered an
      important outcome indicator in substances abuse studies. However, psychometric
      properties of HRQOL measures are largely unknown in people who abuse heroin.
      Therefore, the present study aimed to examine data quality, scaling properties,
      reliability, and construct validity of the 36-Item Short Form healthy survey (SF
      36) in people who abuse heroin. METHODS: A total of 469 people who abuse heroin
      participated in the study. Data quality was determined by data completeness.
      Scaling properties were evaluated by item frequency distribution, equivalence of
      item means and standard deviations, item-internal consistency, and item
      discriminant validity (calculating scaling success). Internal consistency was
      examined using Cronbach's alpha. Construct validity was examined by investigating
      convergent validity and divergent validity among the eight scales of the SF-36.
      RESULTS: The results of data quality showed low missing rates (0.0-3.8%) and high
      completion rates in the scales (91.9-98.7%). The results of scaling assumptions
      showed good item frequency distribution on each item, roughly equivalent item
      means and standard deviations within a scale, good item-internal consistency
      (>0.4) and good scaling success rates (77.5-100%), except on the two scales of
      bodily pain (BP) and social functioning (SF). Three scales showed ceiling and/or
      floor effects [i.e., physical functioning (PF), role limitations due to physical
      problems (RP), and role limitations due to emotional problems (RE)]. Cronbach's
      alpha was acceptable (>0.7), except for the BP and SF scales. Construct validity
      was partially supported by the results of convergent validity and divergent
      validity. CONCLUSION: The results confirmed good data quality; satisfactory
      scaling assumptions and internal consistency (except for the BP and SF scales);
      and generally acceptable construct validity. However, the PF, RP, and RE scales
      showed ceiling and/or floor effects. Therefore, the BP, SF, PF, RP, and RE scales
      should be used with cautions in measuring HRQOL in people who abuse heroin.

PMID- 24685300
TI  - Conjugation of diisocyanate side chains to dimethacrylate reduces polymerization
      shrinkage and increases the hardness of composite resins.
AB  - BACKGROUND/PURPOSE: Polymerization shrinkage is one of the main causes of dental
      restoration failure. This study tried to conjugate two diisocyanate side chains
      to dimethacrylate resins in order to reduce polymerization shrinkage and increase
      the hardness of composite resins. METHODS: Diisocyanate, 2-hydroxyethyl
      methacrylate, and bisphenol A dimethacrylate were reacted in different ratios to
      form urethane-modified new resin matrices, and then mixed with 50 wt.% silica
      fillers. The viscosities of matrices, polymerization shrinkage, surface hardness,
      and degrees of conversion of experimental composite resins were then evaluated
      and compared with a non-modified control group. RESULTS: The viscosities of resin
      matrices increased with increasing diisocyanate side chain density.
      Polymerization shrinkage and degree of conversion, however, decreased with
      increasing diisocyanate side chain density. The surface hardness of all
      diisocyanate-modified groups was equal to or significantly higher than that of
      the control group. CONCLUSION: Conjugation of diisocyanate side chains to
      dimethacrylate represents an effective means of reducing polymerization shrinkage
      and increasing the surface hardness of dental composite resins.

PMID- 24685301
TI  - Factors affecting the diagnostic accuracy of ultrasonography in assessing the
      severity of hepatic steatosis.
AB  - BACKGROUND/PURPOSE: Ultrasonography has long been recognized as a useful tool for
      detecting hepatic steatosis in clinical practice. However, whether it can assess
      the severity of hepatic steatosis and which factors affect its diagnostic
      accuracy remain unclear. METHODS: A total of 171 patients with various causes of
      hepatitis undergoing liver biopsies were retrospectively reviewed. The clinical,
      serologic data and ultrasonographical findings were recorded. Hepatic steatosis
      was graded as negative, mild, moderate, or severe by ultrasonography and
      histology. Histology was used as gold standard and the agreement rates were
      calculated. RESULTS: Our data showed that the agreement rate of ultrasonography
      was 61.4% in assessing the severity of hepatic steatosis and 74.3% in diagnosing
      hepatic steatosis compared with histology (crude kappa=0.46 vs. 0.46). Using
      univariate analyses, body mass index and histology activity index score were
      associated with the agreement in assessing the severity of hepatic steatosis
      (p=0.008 and 0.035), whereas Ishak fibrosis score had a trend association
      (p=0.066). Multivariate analyses indicated that age, body mass index, and Ishak
      fibrosis score could affect the agreement (odds ratio=0.72, 0.89, and 1.41; 95%
      confidence interval=0.54-0.97, 0.83-0.97, and 1.1-1.8). CONCLUSION:
      Ultrasonography could assess the severity of hepatic steatosis with moderate
      accuracy. Obese patients are difficult ultrasonographically. In addition, age and
      hepatic fibrosis could affect the performance of ultrasonography in assessing the
      severity of hepatic steatosis.

PMID- 24685302
TI  - Renal MALT lymphoma associated with Waldenstrom macroglobulinemia.
AB  - Mucosa associated lymphoid tissue lymphoma (MALT lymphoma) is mostly seen in the
      gastrointestinal tract; origin from the kidney is extremely rare. Waldenstrom
      macroglobulinemia (WM) is a clinicopathologic syndrome denoted by the presence of
      monoclonal gammopathy in the serum, typically caused by lymphoproliferative
      disorder. Literature review did not find any report of renal MALT lymphoma
      accompanied by WM. Herein, for the first time, we report a 72 year-old female
      patient with a history of chronic kidney disease, presenting with solitary renal
      mass; MALT lymphoma was confirmed by pathological examination. A serology study
      identified the presence of WM. No manifestation of hyperviscosity syndrome was
      noted. Bone marrow biopsy disclosed the concurrent systemic involvement. Her
      treatment response was uneventful and the renal mass responded with regressive
      change in size after chemotherapy. The renal function remained stable during
      follow-up. MALT lymphoma should be considered as an underlying pathology of
      isolated renal mass. Furthermore, patients with MALT lymphoma should be screened
      for Waldenstrom macroglobulinemia and hyperviscosity syndrome. 

PMID- 24685303
TI  - First microbiologically confirmed case of cryptosporidiosis due to
      Cryptosporidium hominis gp60-If sub-genotype in a patient with HIV-1 infection in
      Taiwan.

PMID- 24685304
TI  - Periportal edema after cardiac arrest due to calcium channel blocker overdose.

PMID- 24685305
TI  - Laparoscopic management of obstructed partial duplex with Y ureteric
      configuration.
AB  - An 11-year-old girl underwent a laparoscopic upper-to-lower moiety
      ureteropyelostomy for lower moiety pelviureteric junction obstruction associated
      with Y ureteric duplication. She presented with left flank pain and was noted to
      be hypertensive with microscopic haematuria on admission. An abdominal ultrasound
      scan revealed a duplex left kidney with gross lower moiety pelvicalyceal
      dilatation. A subsequent MAG-3 scan demonstrated reduced differential function in
      the left lower moiety. A laparoscopic transmesocolic approach confirmed a dilated
      lower moiety pelvis and revealed the Y ureteric duplication. An upper to lower
      moiety ureteropyelostomy and insertion of a JJ stent is described in the
      accompanying video. The child was discharged home on the second day post
      operation. Postoperative imaging showed good decompression and improved
      differential function. The child has been completely well and normotensive at 2
      years' follow-up. 

PMID- 24685306
TI  - T790M mutation is associated with better efficacy of treatment beyond progression
      with EGFR-TKI in advanced NSCLC patients.
AB  - BACKGROUND AND PURPOSE: Continuous EGFR-TKI treatment beyond progression has
      shown promising benefit for some patients with acquired resistance to EGFR-TKIs.
      The aim of this study was to investigate the association of secondary T790M
      mutation at the time of progression with the efficacy of EGFR-TKI treatment
      beyond progression. METHODS: From March 2011 to March 2013, patients with
      advanced NSCLC who developed acquired resistance to EGFR-TKI and where a re
      biopsy was performed at Tongji University Cancer Institute were included into
      this study. Scorpion ARMS was used to detect EGFR mutation status. RESULTS: A
      total of 54 patients were enrolled in this study with a median progression-free
      survival time (PFS1) of 10.9 months according to RECIST criteria. In all, 53.7%
      (29/54) had T790M mutation after the failure of EGFR-TKIs; PFS1 was not
      statistically significantly different between patients with T790M mutation and
      without (13.0 vs. 10.5 months, p = 0.894). In all, 41 patients received TKI
      treatment beyond progression, including 22 with local progression to receive
      additional local therapy and 19 with gradual progression to receive additional
      chemotherapy. The median progression-free survival time (PFS2) of patients who
      received EGFR-TKI beyond progression treatment was 3.5 months (95% CI, 2.689
      4.311). Patients with T790M mutation had significantly longer PFS2 (6.3 vs. 2.6
      months, p = 0.002) and overall survival (39.8 vs. 23.2 months, p = 0.044) than
      those without. CONCLUSION: Patients with secondary T790M mutation at the time of
      progression having gradual or local progression after acquired resistance to EGFR
      TKI benefit more from EGFR-TKI treatment beyond progression compared to those
      without T790M mutation.

PMID- 24685307
TI  - Second line treatment for EGFR wild-type advanced NSCLC: the jury is still out.

PMID- 24685308
TI  - "What is in a name? That which we call a rose. By any other name would smell as
      sweet": towards resolving ambiguity in the TNM Classification for Lung Cancer.

PMID- 24685309
TI  - Development of a New Nordic Diet score and its association with gestational
      weight gain and fetal growth - a study performed in the Norwegian Mother and
      Child Cohort Study (MoBa).
AB  - OBJECTIVE: To construct a diet score for assessing degree of adherence to a
      healthy and environmentally friendly New Nordic Diet (NND) and to investigate its
      association with adequacy of gestational weight gain and fetal growth in a large
      prospective birth cohort. DESIGN: Main exposure was NND adherence, categorized as
      low, medium or high adherence. Main outcomes were adequacy of gestational weight
      gain, described as inadequate, optimal or excessive according to the 2009
      Institute of Medicine guidelines, and fetal growth, categorized as being small,
      appropriate or large for gestational age. Associations of NND adherence with
      gestational weight gain and fetal growth were estimated with multinomial logistic
      regression in crude and adjusted models. SETTING: Norway. SUBJECTS: Women (n 66
      597) from the Norwegian Mother and Child Cohort Study (MoBa). RESULTS: Higher NND
      adherence implied higher energy and nutrient intakes, higher nutrient density and
      a healthier macronutrient distribution. Normal-weight women with high as compared
      with low NND adherence had lower adjusted odds of excessive gestational weight
      gain (OR=0.93; 95 % CI 0.87, 0.99; P=0.024). High as compared with low NND
      adherence was associated with reduced odds of the infant being born small for
      gestational age (OR=0.92; 95 % CI 0.86, 0.99; P=0.025) and with higher odds of
      the baby being born large for gestational age (OR=1.07; 95 % CI 1.00, 1.15;
      P=0.048). CONCLUSIONS: The NND score captures diet quality. Adherence to a
      regional diet including a large representation of fruits and vegetables, whole
      grains, potatoes, fish, game, milk and drinking water during pregnancy may
      facilitate optimal gestational weight gain in normal-weight women and improve
      fetal growth in general.

PMID- 24685310
TI  - Parvalbumin as a metal-dependent antioxidant.
AB  - Parvalbumin (PA) is a Ca(2+)-binding protein of vertebrates massively expressed
      in tissues with high oxygen uptake and respectively elevated level of reactive
      oxygen species (ROS). To characterize antioxidant properties of PA, antioxidant
      capacity (AOC) of intact rat alpha-PA has been explored. ORAC, TEAC and hydrogen
      peroxide AOC assays evidence conformation-dependent oxidation of the PA. AOC
      value for the apo-PA 4-11-fold exceeds that for the Ca(2+)-loaded protein.
      Despite folded conformation of apo-PA, it has AOC equivalent to that of the
      proteolized protein. The most populated under resting conditions PA form, Mg(2+)
      bound PA, has AOC similar to that of apo-PA. ROS-induced changes in absorption
      spectrum of PA evidence an oxidation of PA's phenylalanines in the ORAC assay.
      Sensitivity of PA oxidation to its conformation enabled characterization of its
      metal affinity and pH-dependent behavior: a transition with pKa of 7.6 has been
      revealed for the Ca(2+)-loaded PA. Since total AOC of PA under in vivo conditions
      may reach the level of reduced glutathione, we propose that PA might modulate
      intracellular redox equilibria and/or signaling in a calcium-dependent manner. We
      speculate that the oxidation-mediated damage of some of PA-GABAergic interneurons
      observed in schizophrenia is due to a decline in total AOC of the reduced
      glutathione-PA pair. 

PMID- 24685311
TI  - The neuropsychology of self-reflection in psychiatric illness.
AB  - The development of robust neuropsychological measures of social and affective
      function-which link critical dimensions of mental health to their underlying
      neural circuitry-could be a key step in achieving a more pathophysiologically
      based approach to psychiatric medicine. In this article, we summarize research
      indicating that self-reflection (the inward attention to personal thoughts,
      memories, feelings, and actions) may be a useful model for developing such a
      paradigm, as there is evidence that self-reflection is (1) measurable with self
      report scales and performance-based tests, (2) linked to the activity of a
      specific neural circuit, and (3) dimensionally related to mental health and
      various forms of psychopathology. 

PMID- 24685312
TI  - Patients with type 1 Gaucher disease in South Florida, USA: demographics,
      genotypes, disease severity and treatment outcomes.
AB  - BACKGROUND: Gaucher disease, an autosomal recessive condition due to deficiency
      of lysosomal glucocerebrosidase, is a multisystemic disease, with variable age of
      onset, severity and progression. It is classified into subtypes delineated by the
      absence (type 1) or presence (type 2 and 3) of primary nervous system
      involvement. The ethnically diverse, largely immigrant population in South
      Florida has a spectrum of Gaucher disease phenotypes, creating a challenge for
      optimization of disease management and an opportunity to explore treatment
      patterns. METHODS: Ninety-three records from patients with Gaucher type I in
      South Florida were retrieved from the International Collaborative Gaucher Group
      (ICGG) Registry. Individual genotypes were correlated with severity scores and
      success at achieving published therapeutic goals for haemoglobin concentration,
      platelet count, spleen volume, liver volume and amelioration of bone pain and
      bone crises. RESULTS: The majority of patients were diagnosed during the fifth
      decade of life. Almost two-thirds were homozygous for the N370S mutation,
      reflecting the large Ashkenazi Jewish population in South Florida. The majority
      received imiglucerase (62.8%) at various intervals. 24.5% of patients underwent
      splenectomy before starting enzyme replacement therapy. After a median 12
      treatment years, South Florida patients matched or exceeded the ICCG 4 year
      therapeutic goal achievement for platelet count (85.4% vs. 79.6% success), spleen
      volume (93.3% vs. 78.0% success), liver volume (93.4% vs. 90.6% success), and
      bone crises (100% vs. 99% success). Nevertheless, fewer patients with intact
      spleens had sustained achievement of all 6 therapeutic goals (30.4% versus 41.4%)
      and only 40% of the splenectomy patients sustained achievement of 5/5 possible
      goals. 54.7% of the intact spleen patients continued to have bone pain vs. 29.8%
      in ICCG. Significantly, only 37% of the ICGG patient cohort had bone pain prior
      to initiation of treatment compared to 73.4% of the South Florida patients
      (moderate or severe pain in 59.6%). CONCLUSIONS: Demographic characteristics are
      a significant determinant of the differences in response to treatment observed in
      South Florida Gaucher patients compared to those described in the international
      population enrolled in the ICGG Gaucher Registry. Individual genotypes and ethnic
      background are important considerations for optimizing patient care for Gaucher
      disease.

PMID- 24685314
TI  - Is it time for a "pneumo-geriatrician" for frail old patients with respiratory
      diseases?

PMID- 24685315
TI  - Family factors contribute to general anxiety disorder and suicidal ideation among
      Latina Americans.
AB  - PURPOSE: Despite a rapidly growing Latina/o American population, little is known
      about modifiable factors that could protect Latinas against major psychiatric
      disorders. The present study explored psychosocial risk (Negative Interaction)
      and protective factors (Family Cohesion, Social Support, Religious Involvement,
      Racial and Ethnic Identity) for major depressive disorder (MDD), general anxiety
      disorder (GAD), and suicidal ideation (SI) among Latinas participating in the
      first national mental health epidemiological survey of Latina Americans. METHOD:
      We conducted three sets of logistic regressions, predicting outcomes for 1,427
      Latinas identified in the National Latino and Asian American Study (NLAAS), the
      first nationally representative, epidemiological study of Latino and Asian
      Americans living in the United States. These analyses followed preplanned steps:
      Model 1 used known predictors as controls and Model 2 added psychosocial risk and
      predictive factors beyond the known predictors. RESULTS: For each outcome
      examined, psychosocial risk and protective factors produced a significantly
      better model fit in Model 2 than sociodemographic and acculturation variables
      known to predict mental health outcomes in Model 1. Negative Interactions were
      associated with increased likelihood of GAD and SI, whereas Family Cohesion
      seemed to be protective against GAD. No psychosocial factors predicted MDD.
      CONCLUSIONS: Differential protective and risk factors for major psychiatric
      disorders suggest that assessment and intervention may need certain sex-specific
      components in order to improve health care and prevention for Latinas.

PMID- 24685313
TI  - Management of nontuberculous mycobacterial infection in the elderly.
AB  - The incidence of nontuberculous mycobacteria (NTM) has increased over the last
      decades. Elderly people are more susceptible to NTM and experience increased
      morbidities. NTM incidence is expected to rise due to an increasing elderly
      population at least up to 2050. Given the importance of NTM infection in the
      elderly, an increasing interest exists in studying NTM characteristics in the
      aged population. In this review, we summarize the characteristics of NTM
      infection among elderly patients. We focus on epidemiology, clinical
      presentation, and treatment options of NTM in this age group. We highlight the
      differences in the diagnosis and treatment between rapid and slow growing
      mycobacterial infections. The current recommendation for treatment of NTM is
      discussed. We debate if in vitro susceptibility testing has a role in the
      treatment of NTM. Drug-drug interaction between antibiotics used to treat NTM and
      other medications, particularly warfarin, is another important issue that we
      discuss. Finally, we review the prognosis of NTM disease in elderly patients.

PMID- 24685316
TI  - Adventitial macrophage and lymphocyte accumulation accompanying early stages of
      human coronary atherogenesis.
AB  - BACKGROUND: Atherosclerosis is considered a chronic inflammatory disease of the
      entire arterial wall, including the adventitia. Advanced coronary lesions with
      lipid cores are associated with adventitial inflammation, but the early
      inflammatory process in human coronary adventitia is largely unknown. We
      hypothesized that adventitial inflammatory cell infiltration accompanies the
      early stages of atherogenesis in human coronary arteries, and it is synchronous
      with the inflammatory process in the intima. METHODS: Coronary artery samples
      were obtained from 111 forensic autopsy cases aged from 7 to 25 years.
      Adventitial and intimal macrophages, T lymphocytes and B lymphocytes, and intimal
      microvessels were detected by immunohistochemical methods and quantified by
      computerized image analysis. Body height, weight, waist circumference, and the
      size of mesenteric and omental fat depots were measured. RESULTS: Adventitial
      densities of macrophages and T lymphocytes were significantly higher in arteries
      showing intimal xanthomas than in cases with only scattered intimal macrophages.
      The xanthoma group also had significantly higher body mass index and larger
      visceral fat depots. Highest densities of all adventitial cell types were seen in
      intermediate lesions and fibroatheromas. There were significant positive
      correlations between intimal and adventitial densities of T cells and B cells in
      the groups with or without intimal xanthomas, but the positive correlation
      between intimal and adventitial macrophages was significant only in the group
      without xanthomas. CONCLUSIONS: Adventitial immune-inflammatory cell accumulation
      accompanies the early stages of coronary atherogenesis in young individuals, and
      lymphocyte accumulation seems to be synchronous in the intima and adventitia.
      Macrophage accumulation is also synchronous before xanthomas are seen.

PMID- 24685318
TI  - Changes in maternal serum insulin-like growth factor-1 during pregnancy and its
      relationship to maternal anthropometry.

PMID- 24685317
TI  - iPS cell technologies: significance and applications to CNS regeneration and
      disease.
AB  - In 2006, we demonstrated that mature somatic cells can be reprogrammed to a
      pluripotent state by gene transfer, generating induced pluripotent stem (iPS)
      cells. Since that time, there has been an enormous increase in interest regarding
      the application of iPS cell technologies to medical science, in particular for
      regenerative medicine and human disease modeling. In this review article, we
      outline the current status of applications of iPS technology to cell therapies
      (particularly for spinal cord injury), as well as neurological disease-specific
      iPS cell research (particularly for Parkinson's disease and Alzheimer's disease).
      Finally, future directions of iPS cell research are discussed including a)
      development of an accurate assay system for disease-associated phenotypes, b)
      demonstration of causative relationships between genotypes and phenotypes by
      genome editing, c) application to sporadic and common diseases, and d)
      application to preemptive medicine. 

PMID- 24685319
TI  - Pregnancy and pulmonary hypertension.
AB  - Pulmonary hypertension during pregnancy is associated with considerable risks of
      maternal mortality and morbidity. Our systematic review of the literature on the
      use of targeted treatments for pulmonary arterial hypertension during pregnancy
      indicates a considerable decrease of mortality since a previous review in 1998
      (16% v 38%), and a further non-significant decrease in mortality since the latest
      review in 2009 (16% v 25%). In addition to the use of targeted treatments, the
      timely institution of these treatments, and early planned delivery, may
      contribute to better outcome. Furthermore, research suggests that women with mild
      pulmonary hypertension or favourable functional class may have a better
      prognosis, but there is yet no proof of decreased mortality among these women.
      Despite an improved prognosis, pregnancy is contra-indicated in women with
      pulmonary hypertension and, when pregnancy occurs, termination should be
      considered. When pregnancy continues, management by a multidisciplinary team in a
      specialist centre is indicated. 

PMID- 24685320
TI  - The intravenous and oral pharmacokinetics of afoxolaner used as a monthly
      chewable antiparasitic for dogs.
AB  - The pharmacokinetics of afoxolaner in dogs was evaluated following either
      intravenous or after oral administration of NEXGARD((r)), a soft chewable
      formulation. Afoxolaner is a member of one of the newest classes of antiparasitic
      agents, known as antiparasitic isoxazolines. The soft chewable formulation
      underwent rapid dissolution, and afoxolaner was absorbed quickly following oral
      administration of the minimum effective dose of 2.5mg/kg, with maximum plasma
      concentrations (Cmax) of 1,655 +/- 332 ng/mL observed 2-6h (Tmax) after
      treatment. The terminal plasma half-life was 15.5 +/- 7.8 days, and oral
      bioavailability was 73.9%. Plasma concentration-versus-time curves fit a 2
      compartment model and increased proportionally with dose over the oral dose range
      of 1.0-4.0mg/kg, and over the oral dose range from 1.0 to 40 mg/kg. Following an
      intravenous dose of 1mg/kg, the volume of distribution (Vd) was 2.68 +/- 0.55
      L/kg, and the systemic clearance was 4.95 +/- 1.20 mL/h/kg. Afoxolaner plasma
      protein binding was >99.9% in dogs. One major metabolite, formed following
      hydroxylation of afoxolaner, was identified in dog plasma, urine and bile. When
      afoxolaner is administered orally, there is a strong correlation between
      afoxolaner plasma concentration and efficacy with EC90 values of 23 ng/mL for
      Ctenocephalides felis and >= 100 ng/mL for Rhipicephalus sanguineus sensu lato
      and Dermacentor variabilis. The pharmacokinetic properties of afoxolaner are
      suited for a monthly administration product because the fast absorption and long
      terminal half-life support a rapid onset of action while ensuring month-long
      efficacy.

PMID- 24685321
TI  - Efficacy of afoxolaner against Ixodes scapularis ticks in dogs.
AB  - Efficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Ixodes
      scapularis was evaluated in a laboratory study. One day prior to treatment,
      beagle dogs (n=16) were infested with 50 unfed wild adult ticks. Repeat
      infestations were performed weekly for four additional weeks. The number of live
      ticks remaining on each dog was determined 48 h after treatment and after each
      subsequent infestation. A single oral treatment with a dose approaching the
      minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing
      infestations of I. scapularis ticks and controlled weekly re-infestations, with
      efficacy between 98% and 100% recorded until Day 23 and 94% at Day 30.

PMID- 24685322
TI  - Assessment of the onset of action of afoxolaner against existing adult flea
      (Ctenocephalides felis) infestations on dogs.
AB  - The speed of kill of afoxolaner against experimental infestations by
      Ctenocephalides felis was evaluated after oral administration of afoxolaner in a
      soft chew (NEXGARD((r))) at a dose to achieve 2.5mg/kg bodyweight. Forty beagles
      were allocated to two treatment groups. Dogs in Treatment Group 1 were untreated
      controls. Dogs in Treatment Group 2 were treated on Day-0 with afoxolaner,
      according to their pre-treatment bodyweight. All dogs were infested with
      approximately 100 C. felis on Day-1. Live fleas were counted upon removal at 5
      time points after treatment (i.e., 2, 4, 8, 12 and 24h after treatment). For each
      time point, counts were performed on 4 dogs from each of the treated and the
      untreated groups. Early curative flea killing efficacy was evaluated with respect
      to the untreated control group. The afoxolaner treated group had significantly
      fewer fleas than the untreated control group at 8, 12, and 24h (p<0.001). The
      percent efficacies of orally administered afoxolaner were 15.0%, 87.8%, 99.5%,
      100.0%, and 100.0% at 2, 4, 8, 12, and 24h, respectively. In this study,
      afoxolaner began killing fleas by 2h after treatment with increasing efficacy at
      subsequent time points and had >99.5% efficacy at 8, 12, and 24h after treatment
      demonstrating an early onset of action. 

PMID- 24685323
TI  - A novel vacuum assisted closure therapy model for use with percutaneous devices.
AB  - Long-term maintenance of a dermal barrier around a percutaneous prosthetic device
      remains a common clinical problem. A technique known as Negative Pressure Wound
      Therapy (NPWT) uses negative pressure to facilitate healing of impaired and
      complex soft tissue wounds. However, the combination of using negative pressure
      with percutaneous prosthetic devices has not been investigated. The goal of this
      study was to develop a methodology to apply negative pressure to the tissues
      surrounding a percutaneous device in an animal model; no tissue healing outcomes
      are presented. Specifically, four hairless rats received percutaneous porous
      coated titanium devices implanted on the dorsum and were bandaged with a semi
      occlusive film dressing. Two of these animals received NPWT; two animals received
      no NPWT and served as baseline controls. Over a 28-day period, both the number of
      dressing changes required between the two groups as well as the pressures were
      monitored. Negative pressures were successfully applied to the periprosthetic
      tissues in a clinically relevant range with a manageable number of dressing
      changes. This study provides a method for establishing, maintaining, and
      quantifying controlled negative pressures to the tissues surrounding percutaneous
      devices using a small animal model. 

PMID- 24685324
TI  - Omega-3 fatty acids for postoperative atrial fibrillation: alone or in
      combination with antioxidant vitamins?
AB  - BACKGROUND: The effects of omega-3 polyunsaturated fatty acids (PUFA) on the
      prevention of postoperative atrial fibrillation (POAF) are inconclusive in
      current studies. Moreover, the most appropriate composition of PUFA to play the
      protective role is unclear. The aim of this meta-analysis was to ascertain the
      protective role of PUFA on POAF and the most appropriate composition. METHODS:
      Studies were identified through PubMed, CENTRAL, EMBASE, reviews and reference
      lists of relevant papers. The odds ratio (OR) was calculated for POAF.
      Statistical analyses were performed with Review Manager 5.0. RESULTS: Eleven
      randomised controlled trials with 3137 patients were included in the analysis.
      The use of PUFA alone did not reduce the incidence of POAF compared with the
      control (OR: 0.76; 95% confidence interval [CI]: 0.57-1.03; P=0.08; I(2)=52%).
      However, combination therapy with PUFA and vitamins C and E reduced the incidence
      of POAF by 68% (OR: 0.32; 95%CI: 0.17-0.60; P=0.0005; I(2)=38%). Subgroup
      analysis indicated that the ratio of EPA/DHA 1:2 was effective in preventing POAF
      (OR: 0.35; 95%CI: 0.24-0.50; P<0.00001; I(2)=0%), while the ratio not 1:2 failed.
      CONCLUSIONS: Combination therapy with PUFA and vitamins C and E is effective in
      the prevention of POAF while PUFA alone is not. The ratio of EPA/DHA may
      influence the incidence of POAF, and 1:2 may be most appropriate. Studies about
      PUFA on the prevention of POAF are still worthwhile to be conducted in the
      future.

PMID- 24685325
TI  - Usefulness of the QRS-T angle to improve long-term risk stratification of
      patients with acute myocardial infarction and depressed left ventricular ejection
      fraction.
AB  - In light of the low cost, the widespread availability of the electrocardiogram,
      and the increasing economic burden of the health-related problems, we aimed to
      analyze the prognostic value of automatic frontal QRS-T angle to predict
      mortality in patients with left ventricular (LV) systolic dysfunction after acute
      myocardial infarction (AMI). About 467 consecutive patients discharged with
      diagnosis of AMI and with LV ejection fraction <=40% were followed during 3.9
      years (2.1 to 5.9). From them, 217 patients (47.5%) died. The frontal QRS-T angle
      was higher in patients who died (116.6+/-52.8 vs 77.9+/-55.1, respectively,
      p<0.001). The QRS-T angle value of 90 degrees  was the most accurate to predict
      all-cause cardiac death. After multivariate analysis, frontal QRS-T angle
      remained as an excellent predictor of all-cause and cardiac deaths, increasing
      the mortality 6% per each 10 degrees . For the global mortality, the hazard ratio
      for a QRS-T angle>90 degrees  was 2.180 (1.558 to 3.050), and for the combined
      end point of cardiac death and appropriate implantable cardioverter
      defribrillator therapy, it was 2.385 (1.570 to 3.623). This independent
      predictive value was maintained even after adjusting by bundle brunch block, ST
      elevation AMI, and its localization. In conclusion, a wide automatic frontal QRS
      T angle (>90 degrees ) is a good discriminator of long-term mortality in patients
      with LV systolic dysfunction after an AMI. The ability to easily measure it from
      a standard 12-lead electrocardiogram together with its prognostic value makes the
      frontal QRS-T angle an attractive tool to help clinicians to improve risk
      stratification of those patients.

PMID- 24685326
TI  - Meta-analysis of outcomes after intravascular ultrasound-guided versus
      angiography-guided drug-eluting stent implantation in 26,503 patients enrolled in
      three randomized trials and 14 observational studies.
AB  - There are conflicting data regarding the benefit of intravascular ultrasound
      (IVUS)-guided percutaneous coronary intervention (PCI) over angiography-guided
      PCI. Since the last meta-analysis was published, several new studies have been
      reported. We performed a comprehensive meta-analysis to evaluate the clinical
      impact of IVUS-guided PCI with drug-eluting stent compared with conventional
      angiography-guided PCI. This meta-analysis included 26,503 patients from 3
      randomized and 14 observational studies; 12,499 patients underwent IVUS-guided
      PCI and 14,004 underwent angiography-guided PCI. Main outcome measures were total
      mortality, myocardial infarction (MI), stent thrombosis, and target lesion
      revascularization (TLR). IVUS-guided PCI was significantly associated with more
      stents, longer stents, and larger stents. Regarding clinical outcomes, IVUS
      guided PCI was associated with a significantly lower risk of TLR (odds ratio [OR]
      0.81, 95% confidence interval [CI] 0.66 to 1.00, p=0.046). In addition, the risk
      of death (OR 0.61, 95% CI 0.48 to 0.79, p<0.001), MI (OR 0.57, 95% CI 0.44 to
      0.75, p<0.001), and stent thrombosis (OR 0.59, 95% CI 0.47 to 0.75, p<0.001) were
      also decreased. In conclusion, our meta-analysis demonstrated that IVUS-guided
      PCI was associated with lower risk of death, MI, TLR, and stent thrombosis after
      drug-eluting stent implantation.

PMID- 24685327
TI  - Meta-analysis of clinical correlates of acute mortality in takotsubo
      cardiomyopathy.
AB  - The incidence and clinical correlates of acute in-hospital mortality of takotsubo
      cardiomyopathy (TTC) are not clear. We performed a systematic review and meta
      analysis to consolidate the current evidence on acute mortality in TTC. We then
      assessed the impact of "secondary" TTC, male gender, advancing age, and
      catecholamine use on mortality. A comprehensive search of 4 major databases
      (EMBASE, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their
      inception to the first week of July 2013. We included original research studies,
      recruiting >=10 participants, published in English language, and those that
      reported data on mortality and cause of death in patients with TTC. Of 382
      citations, 37 studies (2,120 patients with TTC) from 11 different countries were
      included in the analyses. The mean age of the cohort was 68 years (95% confidence
      interval [CI] 67 to 69) with female predominance (87%). The in-hospital mortality
      rate among patients with TTC was 4.5% (95% CI 3.1 to 6.2, I2=60.8%). Among all
      deaths, 38% were directly related to TTC complications and rest to underlying
      noncardiac conditions. Male gender was associated with higher TTC mortality rate
      (odds ratio 2.6, 95% CI 1.5 to 4.6, p=0.0008, I2=0%) so was "secondary" TTC (risk
      difference -0.11, 95% CI -0.18 to -0.04, p=0.003, I2=84%). The mean age of
      patients dying tended to be greater than that in the whole cohort (72+/-7 vs 65+/
      7 years). In conclusion, TTC is not as benign as once thought. To reduce the
      mortality rate, greater efforts need to be directed to the diagnosis, treatment,
      and ultimately prevention of "secondary" TTC.

PMID- 24685328
TI  - Cardiotoxicity research in breast cancer patients: past and future.

PMID- 24685329
TI  - Critical role of TNF-alpha-TNFR1 signaling in intracranial aneurysm formation.
AB  - BACKGROUND: Intracranial aneurysm (IA) is a socially important disease due to its
      high incidence in the general public and the severity of resultant subarachnoid
      hemorrhage that follows rupture. Despite the social importance of IA as a cause
      of subarachnoid hemorrhage, there is no medical treatment to prevent rupture,
      except for surgical procedures, because the mechanisms regulating IA formation
      are poorly understood. Therefore, these mechanisms should be elucidated to
      identify a therapeutic target for IA treatment. In human IAs, the presence of
      inflammatory responses, such as an increase of tumor necrosis factor (TNF)-alpha,
      have been observed, suggesting a role for inflammation in IA formation. Recent
      investigations using rodent models of IAs have revealed the crucial role of
      inflammatory responses in IA formation, supporting the results of human studies.
      Thus, we identified nuclear factor (NF)-kappaB as a critical mediator of
      inflammation regulating IA formation, by inducing downstream pro-inflammatory
      genes such as MCP-1, a chemoattractant for macrophages, and COX-2. In this study,
      we focused on TNF-alpha signaling as a potential cascade that regulates NF-kappaB
      mediated IA formation. RESULTS: We first confirmed an increase in TNF-alpha
      content in IA walls during IA formation, as expected based on human studies.
      Consistently, the activity of TNF-alpha converting enzyme (TACE), an enzyme
      responsible for TNF-alpha release, was induced in the arterial walls after
      aneurysm induction in a rat model. Next, we subjected tumor necrosis factor
      receptor superfamily member 1a (TNFR1)-deficient mice to the IA model to clarify
      the contribution of TNF-alpha-TNFR1 signaling to pathogenesis, and confirmed
      significant suppression of IA formation in TNFR1-deficient mice. Furthermore, in
      the IA walls of TNFR1-deficient mice, inflammatory responses, including NF-kappaB
      activation, subsequent expression of MCP-1 and COX-2, and infiltration of
      macrophages into the IA lesion, were greatly suppressed compared with those in
      wild-type mice. CONCLUSIONS: In this study, using rodent models of IAs, we
      clarified the crucial role of TNF-alpha-TNFR1 signaling in the pathogenesis of
      IAs by inducing inflammatory responses, and propose this signaling as a potential
      therapeutic target for IA treatment.

PMID- 24685330
TI  - Mechanisms and physiological roles of K+ efflux from root cells.
AB  - Potassium is the most abundant macronutrient, which is involved in a multitude of
      physiological processes. Potassium uptake in roots is crucial for plants;
      however, K(+) efflux can also occur and has important functions. Potassium efflux
      from roots is mainly induced by stresses, such as pathogens, salinity, freezing,
      oxidants and heavy metals. Reactive oxygen species (ROS) and exogenous purines
      also cause this reaction. The depolarisation and activation of cation channels
      are required for K(+) efflux from plant roots. Potassium channels and
      nonselective cation channels (NSCCs) are involved in this process. Some of them
      are 'constitutive', while the others require a chemical agent for activation. In
      Arabidopsis, there are 77 genes that can potentially encode K(+)-permeable
      channels. Potassium-selective channel genes include 9 Shaker and 6 Tandem-Pore
      K(+) channels. Genes of NSCCs are more abundant and present by 20 cyclic
      nucleotide gated channels, 20 ionotropic glutamate receptors, 1 two-pore channel,
      10 mechanosensitive-like channels, 2 mechanosensitive 'Mid1-Complementing
      Activity' channels, 1 mechanosensitive Piezo channel, and 8 annexins. Two Shakers
      (SKOR and GORK) and several NSCCs are expressed in root cell plasma membranes.
      SKOR mediates K(+) efflux from xylem parenchyma cells to xylem vessels while GORK
      is expressed in the epidermis and functions in K(+) release. Both these channels
      are activated by ROS. The GORK channel activity is stimulated by hydroxyl
      radicals that are generated in a Ca(2+)-dependent manner in stress conditions,
      such as salinity or pathogen attack, resulting in dramatic K(+) efflux from root
      cells. Potassium loss simulates cytosolic proteases and endonucleases, leading to
      programmed cell death. Other physiological functions of K(+) efflux channels
      include repolarisation of the plasma membrane during action potentials and the
      'hypothetical' function of a metabolic switch, which provides inhibition of
      energy-consuming biosyntheses and releasing energy for defence and reparation
      needs. 

PMID- 24685331
TI  - Exome array study did not identify novel variants in Alzheimer's disease.
AB  - Genetic variants so far identified explain a small fraction of the overall
      inherited risk of Alzheimer's disease (AD). We aimed to identify novel genetic
      variants in AD using exome array that contains comprehensive panel. We genotyped
      295,988 variants in 1005 subjects (400 AD cases and 605 controls) using Axiom
      Exome Genotyping Array that contains a pool of variants discovered in over 16
      major human exome sequencing initiatives. Logistic regression analysis and the
      sequence kernel association optimal test were performed. The APOE, APOC1, and
      TOMM40 showed significant associations with AD in the single variant analysis.
      However, no significant association of other variants with AD was observed. This
      exome array study failed to identify novel genetic variants in AD. 

PMID- 24685332
TI  - Elevated parathyroid hormone after parathyroidectomy delays symptom improvement.
AB  - BACKGROUND: Curative parathyroidectomy for primary hyperparathyroidism (PHPT)
      resolves various nonspecific symptoms related to the disease. Between 8% and 40%
      of patients with normocalcemia after parathyroidectomy have persistently elevated
      parathyroid hormone (ePTH) levels at follow-up. We investigated whether ePTH in
      the early postoperative period was associated with the timing of symptom
      improvement. MATERIALS AND METHODS: This prospective study included adult
      patients with PHPT who underwent curative parathyroidectomy from November 2011 to
      September 2012. Biochemical testing at 2 wk postoperatively identified ePTH
      (defined as PTH>72 pg/mL) versus normal PTH (nPTH). A questionnaire administered
      pre- and post-operatively at 6 wk and 6 mo asked patients to rate the frequency
      of 18 symptoms of PHPT on a five-point Likert scale. Student t-tests were used to
      compare pre- with postoperative changes in scores for individual symptoms.
      RESULTS: Of 194 patients who underwent parathyroidectomy, 129 (66%) participated
      in the study. Preoperatively, all patients were symptomatic, with a mean of 13+/
      4 symptoms. Two weeks postoperatively, 20 patients (16%) had ePTH. The percentage
      of patients with postoperative improvement for individual symptoms was compared
      between groups. At the early time point (6 wk), the ePTH group showed less
      improvement in 14 of 18 symptoms. This difference reached statistical
      significance for four symptoms: anxiety, constipation, thirst, and polyuria. By
      the 6-mo time point, these differences had resolved, and symptom improvement was
      similar between groups. CONCLUSIONS: ePTH after curative parathyroidectomy may
      result in a delay in symptom improvement 6 wk postoperatively; however, this
      difference resolves in 6 mo.

PMID- 24685333
TI  - Methylation of CTNNA1 promoter: frequent but not an adverse prognostic factor in
      acute myeloid leukemia.
AB  - The reduced expression of CTNNA1 gene, a putative tumor suppressor gene, has been
      found in several cancers including acute myeloid leukemia (AML). CTNNA1
      expression is regulated by methylation and histone deacetylation. However, the
      clinical significance of CTNNA1 methylation in AML is rarely known. The present
      study was aimed to investigate the methylation status of CTNNA1 promoter region
      using methylation-specific PCR (MSP) and its clinical relevance in Chinese AML
      patients. Patients with CTNNA1 hypermethylation had significantly lower level of
      CTNNA1 transcript than those without CTNNA1 hypermethylation (P=0.031). The
      relationship of CTNNA1 methylation with clinical parameters was evaluated.
      Aberrant hypermethylation of CTNNA1 gene was found in 23.9% (37/155) AML cases.
      The status of CTNNA1 methylation was not correlated with the mutations of seven
      genes (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, N/K-RAS and C/EBPA). There was
      no significant difference in the rates of complete remission (CR) between
      patients with and without CTNNA1 methylation. Although the overall survival (OS)
      time of the CTNNA1-methylated AML was shorter than that of CTNNA1-unmethylated
      group (6 months vs 9 months), the difference was not statistically significant
      (P=0.681). Our data suggest that CTNNA1 methylation is a recurrent event but has
      no influence on prognosis in AML. 

PMID- 24685334
TI  - BLASTPLOT: a PERL module to plot next generation sequencing NCBI-BLAST results.
AB  - BACKGROUND: The development of Next Generation Sequencing (NGS) during the last
      decade has created an unprecedented amount of sequencing data, as well as the
      ability to rapidly sequence specimens of interest. Read-based BLAST analysis of
      NGS data is a common procedure especially in the case of metagenomic samples.
      However, coverage is usually not enough to allow for de novo assembly. This type
      of read-based analysis often creates the question of how the reads that align to
      the same sequence are distributed. The same question applies to preparation of
      primers or probes for microarray experiments. Although there are several packages
      that allow the visualization of DNA segments in relation to a reference, in most
      cases they require the visualization of one reference at a time and the capture
      of screen shots for each segment. Such a procedure could be tedious and time
      consuming. The field is in need of a solution that automates the capture of
      coverage plots for all the segments of interest. RESULTS: We have created
      BLASTPLOT, a PERL module to quickly plot the BLAST results from short sequences
      (primers, probes, reads) against reference targets. CONCLUSIONS: BLASTPLOT is a
      simple to use PERL module that allows the generation of PNG graphs for all the
      reference sequences associated with a BLAST result set.

PMID- 24685335
TI  - 'Imbricated dermal flap': a novel technique for autologous augmentation in
      immediate breast reconstruction after skin-sparing mastectomy.
AB  - This case demonstrates use of a de-epithelialised inferior pole skin flap for a
      more aesthetic result in immediate autologous breast reconstruction. For women
      with medium to large ptotic breasts, utilising the excess tissue following skin
      sparing mastectomy as an auto-prosthesis, adds volume to the breast and improves
      inferior pole aesthetics. This 'imbricated dermal flap' offers an excellent
      addendum to aesthetic breast reconstruction. 

PMID- 24685336
TI  - A prospective validation study of sentinel lymph node biopsy in multicentric
      breast cancer: SMMaC trial.
AB  - BACKGROUND: Multicentric breast cancer is often considered a contra-indication
      for sentinel lymph node (SLN) biopsy due to concerns with sensitivity and false
      negative rate. To assess SLN feasibility and accuracy in multicentric breast
      cancer, the multi-institutional SMMaC trial was conducted. METHODS: In this study
      30 patients with multicentric breast cancer and a clinically negative axilla were
      prospectively included. Periareolar injection of radioisotope and blue dye was
      administered. In all patients SLN biopsy was validated by back-up completion
      axillary lymph node dissection. RESULTS: the SLN was successfully identified in
      30 of 30 patients (identification rate 100%). The incidence of axillary
      metastases was 66.7% (20/30). The false negative rate was 0% (0/20) and the
      sensitivity was 100% (20/20). The negative predictive value was 100% (10/10).
      CONCLUSION: SLN biopsy in multicentric breast cancer seems feasible and accurate
      and should therefore be considered in patients with multicentric breast cancer
      and clinically negative axilla.

PMID- 24685338
TI  - Malignant renal tumors in childhood.

PMID- 24685337
TI  - Metallographic preparation of Zn-21Al-2Cu alloy for analysis by electron
      backscatter diffraction (EBSD).
AB  - Samples of Zn-21Al-2Cu alloy (Zinalco) that will be heavily deformed were
      prepared using five different manual mechanical metallographic methods. Samples
      were analyzed before tensile testing using the orientation imaging microscopy
      electron backscatter diffraction (OIM-EBSD) technique. The effect of type and
      particle size during the final polishing stages for this material were studied in
      order to identify a method that produces a flat, damage free surface with a
      roughness of about 50 nm and clean from oxide layers, thereby producing
      diffraction patterns with high image quality (IQ) and adequate confidence indexes
      (CI). Our results show that final polishing with alumina and silica, as was
      previously suggested by other research groups for alloys that are difficult to
      prepare or alloys with low melting point, are not suitable for manual
      metallographic preparation of this alloy. Indexes of IQ and CI can be used to
      evaluate methods of metallographic preparation of samples studied using the OIM
      EBSD technique. 

PMID- 24685339
TI  - Diverse presentations in pediatric Meckel's diverticulum: a review of 100 cases.
AB  - BACKGROUND: Our objective was to analyze demographics and characteristics of
      Meckel's diverticulum with different manifestations in pediatric patients.
      METHODS: This is a retrospective study in children with symptomatic Meckel's
      diverticulum who underwent resection between September 1998 and October 2010. The
      diagnosis was confirmed by surgery and pathology. Demographic characteristics,
      manifestations, Meckel's scan results, surgical and histological findings were
      analyzed. RESULTS: One hundred symptomatic Meckel's diverticula were identified
      in 74 boys and 26 girls aged from one day to 18 years old over 13 years.
      Depending on whether or not obstruction occurred, the patients were classified
      into two categories. Each category was further subdivided into two diagnostic
      groups: 17 intussusception and 24 non-intussusception bowel obstruction in the
      obstructive category and 44 gastrointestinal bleeding and 15 diverticulitis
      and/or perforation in the non-obstructive category. The sex discrepancy was
      higher in the non-obstructive category than in the obstructive category (male-to
      female, 4.36 vs. 1.73, p < 0.05). Forty-one of 44 patients with gastrointestinal
      bleeding underwent a Meckel's scan with a high positive rate (92.7%). The ectopic
      tissues were identified in 73 patients and included 61 gastric type, two
      pancreatic type and 10 mixed type. Ectopic tissues were more prevalent in non
      obstructive category (p < 0.05) with ectopic gastric tissue even more pronounced
      (p < 0.01). Ectopic pancreatic tissue was significantly more prevalent in
      intussusception (p < 0.01). Laparoscopic surgery was performed more frequently in
      Meckel's diverticulum with non-obstructive symptoms (p < 0.001). CONCLUSION:
      Diverse presentations in pediatric Meckel's diverticulum are affected by
      different ectopic tissue types and male sex. Laparoscopic surgery is widely used
      for children with non-obstructive symptoms.

PMID- 24685340
TI  - Bronchial platelet-activating factor receptor in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Bacteria expressing phosphorylcholine (ChoP) co-opt host-expressed
      platelet-activating factor receptor (PAFR) to adhere to lower airway cells.
      Cigarette smoke and rhinovirus (RV) infection upregulate PAFR-dependent bacterial
      adhesion to airway cells in vitro, and in healthy adults smoking increases the
      proportion of PAFR positive bronchial epithelial cells. To date the effect of
      chronic obstructive pulmonary disease (COPD) on smoke-induced PAFR is unknown. We
      therefore sought to test the hypothesis that bronchial PAFR mRNA expression is
      increased in smokers with chronic obstructive pulmonary disease (COPD), and
      further increases after RV infection. METHODS: Endobronchial biopsies were
      obtained by fibreoptic bronchoscopy from healthy non-smokers, smokers without
      airway obstruction, and smokers with COPD, before and after infection with
      rhinovirus (RV) serotype 16. Endobronchial PAFR mRNA expression was assessed by
      quantitative PCR and expressed as a ratio of glyceraldehyde-3-phosphate
      dehydrogenase. The distribution of PAFR was assessed by immunohistochemistry.
      RESULTS: Baseline PAFR mRNA expression was increased (p < 0.05) in smokers (n =
      16), and smokers with COPD (n = 14) compared with non-smokers (n = 18). In RV16
      infected subjects there was no increase in PAFR mRNA expression in either non
      smokers (n = 9), smokers (n = 8), or smokers with COPD (n = 7). PAFR
      immunoreactivity in all 3 groups was predominately restricted to the bronchial
      epithelium and submucosal glands. CONCLUSIONS: Endobronchial PAFR mRNA is
      increased in both smokers without airway obstruction and smokers with COPD. We
      found preliminary evidence that RV16 infection does not increase PAFR mRNA
      expression in either smokers or smokers with COPD.

PMID- 24685341
TI  - Recurrent hemichorea after a hypoglycemic episode.

PMID- 24685342
TI  - Diabetes is associated with postural and cognitive domains in Parkinson's
      disease. Results from a single-center study.

PMID- 24685343
TI  - Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's
      disease.
AB  - BACKGROUND: In Parkinson's disease (PD), chronic pain is a common symptom which
      markedly affects the quality of life. Some physiological arguments proposed that
      Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in
      PD. METHODS: We investigated in 58 PD patients the effect of STN-DBS on pain
      using the short McGill Pain Questionnaire and other pain parameters such as the
      Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the
      Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. RESULTS:
      All pain scores were significantly improved 12 months after STN-DBS. This
      improvement was not correlated with motor improvement, depression scores or L
      Dopa reduction. CONCLUSIONS: STN-DBS induced a substantial beneficial effect on
      pain in PD, independently of its motor effects and mood status of patients.

PMID- 24685344
TI  - NIMRAD - a phase III trial to investigate the use of nimorazole hypoxia
      modification with intensity-modulated radiotherapy in head and neck cancer.

PMID- 24685345
TI  - Do screening trial recruitment logs accurately reflect the eligibility criteria
      of a given clinical trial? Early lessons from the RAVES 0803 trial.
AB  - AIMS: Maintaining clinical trial screening logs and reporting data from such logs
      are given importance due to the relevance of a trial's patient population to the
      generalisability of its findings. However, screening logs may not always reflect
      a clinical trial's true target population. The aim of the present study was to
      define and compare 'apparent recruitment' to a trial as captured in a clinical
      trial screening log with 'true recruitment', which considers all potentially
      eligible patients. The Trans Tasman Radiation Oncology Group (TROG) 0803 RAVES
      clinical trial was used to examine the above. MATERIALS AND METHODS: A
      prospective, surgical database was interrogated for the 12 month period to
      identify patients potentially eligible for the TROG 0803 RAVES trial. Information
      on whether patients were referred to a RAVES trial recruitment site and reasons
      for non-referral were obtained. RESULTS: Of 92 men undergoing radical
      prostatectomy, 28 met the RAVES clinical trial eligibility criteria. Fifteen of
      the 28 eligible men were assessed at a RAVES trial site, with five being
      ultimately recruited to RAVES (33% 'apparent recruitment fraction' as captured by
      the site's trial screening log). The 'true recruitment fraction' was 5/28 (18%).
      CONCLUSION: Screening logs at a recruiting trial site may underestimate the
      trial's target population and overestimate recruitment. Only a subpopulation of
      all eligible patients may be captured in trial screening logs and subsequently
      reported on. This may affect the generalisability of the trial's reported
      findings.

PMID- 24685346
TI  - Re-emphasizing the role of copious water irrigation in the first aid treatment of
      chemical burns.

PMID- 24685347
TI  - The hazards of dynamic airflow mattresses and overlays.

PMID- 24685348
TI  - Creation of a standardized burn course for Low Income Countries: meeting local
      needs.
AB  - INTRODUCTION: Standardized courses for the care of the burn patient have
      historically been developed in High Income Countries (HIC). These courses do not
      necessarily reflect the challenges and needs of Low Income Countries (LIC) and
      some components may not be relevant there (i.e. use of ventilators in a country
      that has no or very limited number of ventilators). We are developing a Burn
      Management Course for East Africa. This course was created and trialed in a LIC
      and subsequently a formal manual and course curriculum created. Recently the
      first iteration of the course was undertaken in a major regional burn centre in
      East Africa. We present participant feedback on the course content, and potential
      future directions for course development. OBJECTIVE: (1) To evaluate the ability
      of a standardized burn course for LIC to meet the needs of the participants. (2)
      To explore characteristics of burn care and needs related to delivery of burn
      care in LIC. METHODS: 21 students participated in a multidisciplinary burn
      management course. They were asked to complete an anonymous questionnaire at the
      end of the course. RESULTS: There were 11 nurses, 6 doctors, a physiotherapist,
      occupational therapist, and a dietician. 15 worked in either the adult or
      pediatric burn units, the other six worked in emergency, ICU or the operating
      room. The majority of respondents (56%) had less than 3 years of experience
      working with burn patients. Overall agreement that the course met their
      objectives was rated as 4.6 out of 5. As well the students agreement that they
      had a better understanding of burn injury was rated as 4.8/5. 55.6% indicated
      that scalds were the most commonly seen injury followed by 27.8% responding that
      flames were the most common. Some responses to the question of top difficulties
      facing the caregivers were similar to HIC: staffing shortages, bed shortages, and
      finding useable donor site in large burns. Other responses highlighted the
      challenges these care givers face: poverty stricken patients, not enough
      appropriate food available, and deficiencies in infection control practices.
      CONCLUSION: It is possible to create a course that translates knowledge from a
      HIC setting to meet the needs of the end-user in a LIC setting.

PMID- 24685349
TI  - Comparison of the Berlin definition with the American European consensus
      definition for acute respiratory distress syndrome in burn patients.
AB  - OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a leading cause of
      mortality in burn patients. Smoke inhalation, pneumonia and inflammation process
      are the major causes of ARDS in burn patients. The American European Consensus
      Conference (AECC) definition proposed in 1994 has recently been revised by the
      Berlin definition. Our objective was to describe the epidemiology of ARDS
      comparing the Berlin definition with the AECC definition in a retrospective
      cohort of burn patients. METHODS: We reviewed admitted burn adult patients for a
      two year period, and investigated patient who received mechanical ventilation for
      more than 48 h and in whom pneumonia was diagnosed. RESULTS: 40 patients were
      analyzed. According to the AECC definition, 11 patients met criteria for ALI
      (27.5%), and 29 patients for ARDS (72.5%). According to the Berlin definition,
      all patients met criteria for ARDS: 4 (10%) for a severe ARDS, 25 (62.5%) for a
      moderate ARDS, 11 (27.5%) for a mild ARDS. Inhalation injury was diagnosed in 10
      patients (25%). Categorizing patients with the Berlin definition showed
      statistically significative difference of mortality within the three groups, but
      not with the AECC definition. CONCLUSION: The Berlin definition seems to be more
      accurate than the AECC definition to assess the severity of ARDS in term of
      outcome in burn patients. This definition may facilitate prompt recognition of
      ARDS in burn patients, and promote protective ventilation strategy to a larger
      number of patients.

PMID- 24685350
TI  - Working time and workload of nurses: the experience of a burn center in a high
      income country.
AB  - We conducted a one-month study of the working time and workload of nurses in a 15
      beds burn center (including 8 intensive care beds). Nurses' tasks were
      categorized according to their nature (medical care, local treatments, post
      anesthetic monitoring, administrative time related to health care, administrative
      time unrelated to health care, cleaning, rest). The time taken to complete a
      given task was measured for each task. The time devoted to walk and unavailable
      for patients care was also measured. Our study revealed that work distribution
      was far from optimal since administrative tasks occupy more than 30% of workload.
      This represents inefficiency and the literature shows that when time is saved
      from administrative work it is reinvested in health care. One third of the
      administrative tasks are unrelated to care and thus could be performed by non
      specialized clerks. The other two third of the administrative workload are
      closely linked to care. An answer to reduce administrative time lost to care
      activities is the implementation of dedicated ICU software which carries several
      other advantages such as reducing the use of paper, improving the safety of
      prescriptions, automating repetitive and unrewarding tasks and saving physician
      time. This expensive solution can be quickly repaid through costs containment due
      to the time saved. A significant part of the working time is spent walking but
      reducing the ambulatory time may be considered only through structural
      improvements. 

PMID- 24685351
TI  - The evaluation of nasal mupirocin to prevent Staphylococcus aureus burn wound
      colonization in routine clinical practice.
AB  - BACKGROUND: Staphylococcus aureus wound colonization frequently occurs in
      patients with burns and can cause impaired wound healing. Nasal mupirocin
      application may contribute to the reduction of burn wound colonization of
      endogenous origin, whereas colonization by the exogenous route can be reduced by
      blocking cross-infection from other sources. In this study we evaluated whether
      the implementation of routine treatment of patients and burn center personnel
      using nasal mupirocin ointment reduces S. aureus burn wound colonization.
      METHODS: We composed three study groups, consisting of a control period
      (Control), a mupirocin period (MUP), in which patients with burns were all
      receiving nasal mupirocin at admission, and a mupirocin+personnel period (MUP+P),
      in which we also screened the burn center personnel and decolonized S. aureus
      carriers by nasal mupirocin. RESULTS: The patients who carried S. aureus in their
      nose and did not have S. aureus burn wound colonization at admission were
      considered as patients susceptible for the use of nasal mupirocin. In these
      patients, the S. aureus burn wound colonization rate was the same in all study
      groups. S. aureus nasal carriage was a significant independent risk factor for
      burn wound colonization (OR: 3.3; 95% CI: 1.4-7.6) when analyzed within the three
      study groups. CONCLUSION: Although S. aureus carriage is a significant risk
      factor for developing burn wound colonization, the routine use of nasal mupirocin
      did not contribute to a reduction of burn wound colonization.

PMID- 24685352
TI  - Classification of quality of life subscales within the ICF framework in burn
      research: identifying overlaps and gaps.
AB  - OBJECTIVE: Quality of life (QOL) is one of the leading outcomes in burn care
      research. This study classifies subscales of common QOL measures within the
      International Classification of Functioning disability and health (ICF) framework
      to determine to which extent the measures are complementary or overlapping and to
      investigate whether the instruments are able to describe the full spectrum of
      patients' functioning. METHODS: A literature search was performed to determine
      the most frequently used questionnaires in burn research. The subscales of the
      three mostly used questionnaires were classified within the ICF framework.
      RESULTS: Two generic measures, the Short Form-36 items (SF-36) and the European
      Quality of Life 5 Dimensions (EQ-5D), and a disease specific measure, the Burn
      Specific Health Scale-Brief (BSHS-B), were analyzed. The BSHS-B covered most
      domains and was the only scale that included personal factors. The SF-36 included
      only one domain in the activity limitations and similar to the EQ-5D no
      contextual factors were included. Environmental factors were not addressed in the
      questionnaires, even though these may have an impact on the quality of life in
      patients with burns. CONCLUSION: To capture the full spectrum of dysfunctioning a
      combination of the BSHS-B with a generic questionnaire seems obligatory. However
      still some domains of functioning remain uncovered.

PMID- 24685353
TI  - Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain.
AB  - INTRODUCTION: Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG)
      are present in some neuromyelitis optica patients who lack antibodies against
      aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the
      central nervous system have not been investigated in vivo. We microinjected MOG
      IgG, obtained from patients with neuromyelitis optica, into mouse brains and
      compared the results with AQP4-IgG. RESULTS: MOG-IgG caused myelin changes and
      altered the expression of axonal proteins that are essential for action potential
      firing, but did not produce inflammation, axonal loss, neuronal or astrocyte
      death. These changes were independent of complement and recovered within two
      weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal
      and astrocyte death with limited recovery at two weeks. CONCLUSIONS: These
      differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG
      patients and raise the possibility that MOG-IgG contributes to pathology in some
      neuromyelitis optica patients.

PMID- 24685354
TI  - Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: a relationship study.
AB  - OBJECTIVE: This study examines a possible relationship between Ehlers-Danlos
      Syndrome (EDS) and Postural Tachycardia Syndrome (POTS). DESIGN/METHODS: We
      retrospectively reviewed 109 medical records of patients suffering from autonomic
      dysfunction exhibiting at least one POTS symptom from one urban clinic for EDS
      and POTS diagnoses between 2006 and 2013. The presence of EDS within the POTS and
      non-POTS populations was calculated and compared to that of the general
      population. RESULTS: The review revealed 39 (36F:3M) patients with POTS (mean +/-
      SD age, 32.5 +/- 11.8 years) with 7 cases of EDS yielding a prevalence of 18%
      (95% exact CI: 8%, 34%), a statistically significant difference from the
      suggested prevalence of EDS in the general population of 0.02% (p<0.0001). 70
      patients (53F:17M) without POTS (mean +/- SD age, 51.1 +/- 14.7 years) contained
      3 cases of EDS, yielding a prevalence of 4% (95% exact CI: 1%, 12%), a
      statistically significant difference from the general population (p<0.0001). The
      prevalence of EDS was significantly higher in the POTS group compared to the non
      POTS group (p=0.0329). The odds ratio comparing the odds of EDS for POTS versus
      non-POTS patients is 4.9 (95% CI: 1.2, 20.1). CONCLUSION: The presence of EDS may
      be significantly higher in patients with POTS than that of the general population
      and in autonomic patients without POTS. We suspect an additional underlying
      mechanism of POTS caused by EDS.

PMID- 24685355
TI  - Role of NMDA receptors in noise-induced tau hyperphosphorylation in rat
      hippocampus and prefrontal cortex.
AB  - Chronic noise exposure has been associated with abnormalities in glutamate (Glu)
      NMDAR signaling and tau hyperphosphorylation. However, further studies are
      necessary to clarify potential causal relationships. The aim of the present study
      was to evaluate the role of NMDA receptors in noise-induced tau
      hyperphosphorylation in the rat hippocampus and prefrontal cortex. Male Wistar
      rats were randomly divided into three groups in the present study: control with
      isotonic saline instillation (n=10); noise exposure (100 dB SPL white noise, 4h/d
      * 14d) and treated with saline (n=10); and noise exposure and treated with MK-801
      (0.5mg/kg, intraperitoneally; n=10). The levels of tau phosphorylated at Ser202
      and Ser396, and proteins involved in hyperphosphorylation, namely glycogen
      synthase kinase 3beta (GSK3beta) and protein phosphatase 2A (PP2A), were measured
      in the hippocampus and prefrontal cortex (PFC) after the last noise exposure. We
      showed that phosphorylated tau levels were enhanced in noise-exposed-rat
      hippocampus and PFC. MK-801 decreased the hyperphosphorylation of tau at Ser202
      and Ser396 sites in the hippocampus and PFC. Furthermore, MK-801 reversed noise
      induced GSK3beta overexpression but had no significant effect on PP2A levels.
      This suggests that MK-801 protects against chronic-noise-induced tau
      hyperphosphorylation in the hippocampus and PFC. These findings demonstrate that
      Glu-NMDAR signaling may be involved in triggering aberrant tau
      hyperphosphorylation in the hippocampus and PFC after chronic noise exposure.

PMID- 24685356
TI  - Stage III non-small-cell lung cancer: Establishing a benchmark for the proportion
      of patients suitable for radical treatment.
AB  - INTRODUCTION: Outcome data from Cancer Care Ontario suggest that only 27% of
      patients with stage III non-small-cell lung cancer (NSCLC) receive
      chemoradiotherapy. However, many patients are not suitable for radical treatment.
      This study aimed to determine the proportion of patients with stage III NSCLC
      suitable for radical treatment and to examine reasons for choosing a palliative
      approach otherwise. PATIENTS AND METHODS: This was a retrospective cohort study
      of patients with newly diagnosed stage III NSCLC treated between July 1, 2007,
      and June 30, 2009, at the Juravinski Cancer Centre, Canada. Data collected
      included patient demographics, clinical characteristics, treatment, and outcomes.
      RESULTS: A total of 122 patients with stage III NSCLC were included. Additional
      data on 37 patients with stage IV NSCLC and pleural effusions (previously stage
      IIIB) are included for comparison. Of the 122 patients, 61 (50%) received radical
      treatment and 61 (50%) were treated palliatively. Reasons for excluding patients
      from radical treatment were weight loss (WL) > 10% within 3 months of
      presentation (11%), performance status (PS) > 2 (16%), or combined poor PS and WL
      (33%). Significant comorbid health problems excluded only 15% of patients from
      radical treatment. The median overall survival (OS) for patients treated
      radically was 23.3 months versus 7.0 months for those treated palliatively.
      Patients with poor PS or WL > 10% had OS similar to that of patients with stage
      IV pleural effusion (7.1 months vs. 7.2 months). Patients with poor PS and WL >
      10% had the poorest survival (3 months). CONCLUSION: The present data do not
      support extrapolating radical treatment of stage III NSCLC beyond the eligibility
      criteria used in clinical trials. These data serve as a benchmark for the
      assessment of quality of care for patients with stage III NSCLC.

PMID- 24685357
TI  - Glomus tumors in individuals with neurofibromatosis type 1.
AB  - BACKGROUND: Glomus tumors have recently been reported in individuals with the
      neurofibromatosis type 1 (NF1) cancer disposition syndrome. We compare the
      clinical and molecular features of these painful hamartomas in a series of
      sporadic and NF1-associated cases. OBJECTIVE: We sought to evaluate the
      association of NF1 with glomus tumors and to compare NF1-associated glomus tumors
      with sporadic glomus tumors. METHODS: We conducted a retrospective cohort study
      of all individuals with a histopathologic diagnosis of glomus tumor at a large
      tertiary care center from January 1998 to January 2013. Charts were reviewed for
      a coexisting diagnosis of NF1. RESULTS: A total of 42 glomus tumors were
      identified in 34 individuals. Twelve (28.6%) were found in 6 patients with NF1.
      In 28 individuals with 30 sporadic tumors, there was no coexisting medical
      condition. Although multifocal tumors (16.7%) and tumor recurrence (33.3%) were
      more common in association with NF1, these trends did not reach statistical
      significance. NF1-associated glomus tumors exhibited no neurofibromin
      immunoreactivity, whereas their sporadic counterparts retained neurofibromin
      expression. LIMITATIONS: The retrospective design resulted in incomplete data
      capture. CONCLUSIONS: Detection of glomus tumors should raise suspicion for a
      concurrent diagnosis of NF1.

PMID- 24685358
TI  - Turning the tide? Changes in treatment rates for keratinocyte cancers in
      Australia 2000 through 2011.
AB  - BACKGROUND: Keratinocyte cancers (basal cell carcinoma, squamous cell carcinoma)
      are the commonest cancers in human beings. Population data on incidence trends
      are scant because few jurisdictions reliably record diagnoses or treatments.
      OBJECTIVE: We sought to examine temporal trends of treating keratinocyte cancers
      in Australia. METHODS: We analyzed Medicare Australia data relating to the
      diagnosis and treatment of keratinocyte skin cancer between 2000 and 2011. We
      examined counts and rates for each procedure, and the average annual percentage
      rate of change. RESULTS: There were significant increases in excision rates for
      keratinocyte cancers (3.3% per annum for men and 2.2% per annum for women),
      however temporal trends differed significantly by age group. Although annual
      increases in excision rates were highest for men aged 75 to 84 years (8.6% per
      annum), they declined significantly for men and women younger than 45 years. Skin
      biopsy rates increased substantially in all age groups over the study period,
      suggesting no lessening in skin cancer surveillance in any age group.
      LIMITATIONS: The Medicare data do not include services provided in public
      hospitals, however fewer than 2% of skin cancers are treated in these settings.
      CONCLUSIONS: Although overall treatment rates for keratinocyte cancers have
      increased substantially during the past decade, excision rates are declining in
      younger Australians.

PMID- 24685359
TI  - High-energy resolution electron energy-loss spectroscopy study of interband
      transitions characteristic to single-walled carbon nanotubes.
AB  - An electron energy-loss spectroscopic (EELS) study using a monochromator
      transmission electron microscope was conducted for investigating the dielectric
      response of isolated single-walled carbon nanotubes (SWCNTs) owing to interband
      transitions characteristic to chiral structures. Individual chiral structures of
      the SWCNTs were determined by electron diffraction patterns. EELS spectra
      obtained from isolated SWCNTs showed sharp peaks below pi plasmon energy of 5 eV,
      which were attributed to the characteristic interband transitions of SWCNTs. In
      addition, unexpected shoulder structures were observed at the higher energy side
      of each sharp peak. Simulations of EELS spectra by using the continuum dielectric
      theory showed that an origin of the shoulder structures was because of the
      surface dipole mode along the circumference direction of the SWCNT. It was
      noticed that the electron excitation energies obtained by EELS were slightly
      higher than those of optical studies, which might be because of the inelastic
      scattering process with the momentum transfers. To interpret the discrepancy
      between the EELS and optical experiments, it is necessary to conduct more
      accurate simulation including the first principle calculation for the band
      structure of SWCNTs. 

PMID- 24685360
TI  - Youth victimization in Sweden: prevalence, characteristics and relation to mental
      health and behavioral problems in young adulthood.
AB  - The present study examines multiple types of victimization simultaneously, their
      prevalence and characteristics in childhood and adolescence, and it examines the
      associations between victimization and poly-victimization on the one hand and
      single and multiple mental health and behavioral problems on the other. The
      sample consisted of 2,500 Swedish young adults (20-24 years) who provided
      detailed report of multiple types of lifetime victimization and current health
      and behaviors via an interview and a questionnaire. Results showed that it was
      more common to be victimized in adolescence than in childhood and more common to
      be victimized repeatedly rather than a single time, among both males and females.
      Males and females were victimized in noticeably different ways and partially at
      different places and by different perpetrators. With regard to mental health and
      behavioral problems, anxiety, post-traumatic stress, self-harm, and criminality
      were clearly overrepresented among both males and females who had experienced any
      type of victimization. Poly-victimization was related to single and multiple
      mental health and behavioral problems among both males and females. We conclude
      that professionals need to conduct thorough evaluations of victimization when
      completing mental health assessments among troubled youths, and that youth might
      benefit from the development of interventions for poly-victimized youth. 

PMID- 24685361
TI  - Beta-blockade and noncardiac surgery.

PMID- 24685362
TI  - Polyuria after cessation of vasopressin in a child after cardiac surgery.

PMID- 24685363
TI  - The clinical impact of inpatient hypoglycemia.
AB  - Hypoglycemia is common in hospitalized patients and is associated with poor
      outcomes, including increased mortality. Older individuals and those with
      comorbidities are more likely to suffer the adverse consequences of inpatient
      hypoglycemia. Observational studies have shown that spontaneous inpatient
      hypoglycemia is a greater risk factor for death than iatrogenic hypoglycemia,
      suggesting that hypoglycemia acts as a marker for more severe illness, and may
      not directly cause death. Initial randomized controlled trials of intensive
      insulin therapy in intensive care units demonstrated improvements in mortality
      with tight glycemic control, despite high rates of hypoglycemia. However, follow
      up studies have not confirmed these initial findings, and the largest NICE-SUGAR
      study showed an increase in mortality in the tight control group. Despite these
      recent findings, a causal link between hypoglycemia and mortality has not been
      clearly established. Nonetheless, there is potential for harm from inpatient
      hypoglycemia, so evidence-based strategies to treat hyperglycemia, while
      preventing hypoglycemia should be instituted, in accordance with current practice
      guidelines.

PMID- 24685365
TI  - Helicobacter pylori infection, insulin resistance and nonalcoholic fatty liver
      disease.

PMID- 24685364
TI  - Carotid intima-media thickness is reduced 12 months after gastric bypass surgery
      in obese patients with type 2 diabetes or impaired glucose tolerance.
AB  - AIM: To investigate whether Roux-en-Y gastric bypass surgery (RYGB) - an in vivo
      model for normalisation of hyperglycaemia - improves carotid intima-media
      thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance
      (IGT) and normal glucose tolerance (NGT). METHODS: Observational prospective
      study, 34 obese patients (T2D (n = 14)/IGT (n = 4), and NGT (n = 16)) were
      investigated before and six and 12months after RYGB. RESULTS: Mean carotid IMT
      was significantly reduced 12months after RYGB in patients with T2D/IGT (-0.041 mm
      (95% CI -0.069; -0.012, p = 0.005)) but not in patients with NGT (-0.010 mm (
      0.039; 0.020, p = 0.52)). The between-group difference was not significant
      (p=0.13). Twelve months after RYGB, patients with respectively T2D/IGT and NGT
      demonstrated changes in weight: -29.9 kg, p<0.001/-30.6 kg, p < 0.001, HbA1c: 
      0.7%, p < 0.001/-0.1%, p = 0.33, systolic blood pressure: -2 mmHg, p = 0.68/-10
      mmHg, p = 0.01 and diastolic blood pressure: -8 mmHg, p = 0.003/-11 mmHg, p <
      0.001. 80% of T2D patients terminated antihyperglycaemic medication. CONCLUSION:
      Mean carotid IMT was significantly reduced 12months after RYGB in patients with
      T2D/IGT which provides evidence to support that the earliest atherosclerotic
      changes in the arterial wall are reversible. Although numerically different from
      the changes observed in patients with NGT, the between-group difference was not
      statistically significant.

PMID- 24685366
TI  - [Diarrhea associated with Clostridium difficile in the elderly: new
      perspectives].
AB  - Infection due to Clostridium difficile is currently the main cause of hospital
      acquired gastrointestinal disease. Its prevalence in the elderly population is
      higher due to there being many associated risk factors in this age group, such as
      comorbidity, frequent exposure to the healthcare or residential home setting,
      immunosenescence, greater consumption of antibiotics, and antiacids. The
      diagnostic techniques have notably improved in the last few years, which could
      also account for an increase in its diagnosis. The new expert consensus
      recommendations propose stratifying the clinical situation of the patient in
      order to choose the treatment option. Therapeutic options have recently been
      included in the new Clinical Guidelines, such as flidaxomicin or fecal
      transplants, with encouraging results, particularly for the control of frequent
      recurrences. 

PMID- 24685367
TI  - Electromyographic response of shoulder muscles to acute experimental subacromial
      pain.
AB  - This study investigated effects of experimentally-induced subacromial pain,
      induced via hypertonic saline injection, on shoulder muscles activity.
      Electromyographic activity of 20 healthy participants was assessed for humeral
      elevation and descent for the control and experimental pain conditions, using
      fine wire electrodes for subscapularis and supraspinatus and surface electrodes
      for middle deltoid, upper trapezius, lower trapezius, infraspinatus, and serratus
      anterior. Normalized mean amplitudes were analyzed for each muscle for four
      phases for elevation and descent, respectively. Repeated measures analysis of
      variances (ANOVAs) were used to determine differences between muscle activity in
      the control and experimental condition for the four phases of elevation and
      descent. Differences for mean normalized amplitudes were not significant during
      humeral elevation. Increased activity was found for the pain condition for
      serratus anterior and middle deltoid during the first (120-90 degrees ) and third
      (60-30 degrees ) parts and decreased activity for infraspinatus in the second
      half of descent (60-0 degrees ). No significant differences were found during
      descent for upper and lower trapezius, subscapularis and supraspinatus. While
      increased serratus anterior activity during 60-30 degrees  of descent may be
      protective, increased middle deltoid and decreased infraspinatus activity during
      the same range may threaten subacromial tissues in that range. Overall the
      changes in muscle activation were individual specific, particularly during the
      concentric elevation phase.

PMID- 24685368
TI  - Multiple pregnancies following assisted reproductive technologies--a happy
      consequence or double trouble?
AB  - The association between assisted reproduction technologies (ART) and multiple
      pregnancy is well-established, with a multiple birth rate of 24% in ART
      pregnancies. Multiple pregnancy is associated with significantly increased
      maternal and perinatal morbidity and mortality, as well as increased costs to the
      National Health Service. Evidence relating to the obstetric outcomes of ART twins
      versus naturally conceived twins is discussed in this review. Methods to reduce
      the risk of multiple births including elective single embryo transfer and
      multifetal pregnancy reduction are also discussed. 

PMID- 24685369
TI  - Ultra minimally invasive sonographically guided carpal tunnel release: an
      external pilot study.
AB  - BACKGROUND: Authors have reported better outcomes, by reducing surgical
      dissection for carpal tunnel syndromes requiring surgery. Recently, a new
      sonographically guided technique for ultra minimally invasive (Ultra-MIS) carpal
      tunnel release (CTR) through 1mm incision has been described. HYPOTHESIS: We
      hypothesized that a clinical trial for comparing Ultra-MIS versus Mini-open
      Carpal Tunnel Release (Mini-OCTR) was feasible. MATERIALS AND METHODS: To test
      our hypothesis, we conducted a pilot study for studying Ultra-MIS versus Mini
      OCTR respectively performed through a 1mm or a 2 cm incision. We defined success
      if primary feasibility objectives (safety and efficacy) as well as secondary
      feasibility objectives (recruitment rates, compliance, completion, treatment
      blinding, personnel resources and sample size calculation for the clinical trial)
      could be matched. Score for Quick-DASH questionnaire at final follow-up was
      studied as the primary variable for the clinical trial. Turnover times were
      studied for assessing learning curve stability. RESULTS: Forty patients were
      allotted. Primary and secondary feasibility objectives were matched with the
      following occurrences: 70.2% of eligible patients finally recruited; 4.2% of
      randomization refusals; 26.6 patients/month recruited; 100% patients receiving a
      blinded treatment; 97.5% compliance and 100% completion. A sample size of 91
      patients was calculated for clinical trial validation. At final follow-up,
      preliminary results for Quick-Dash substantially favored Ultra-MIS over Mini-OCTR
      (average 14.54 versus 7.39) and complication rates were lower for Ultra-MIS (5%
      versus 20%). A stable learning curve was observed for both groups. CONCLUSIONS:
      The clinical trial is feasible. There is currently no evidence to contraindicate
      nor withhold the use of Ultra-MIS for CTR. LEVEL OF EVIDENCE: III.

PMID- 24685370
TI  - Strategies for the management of adverse events associated with mTOR inhibitors.
AB  - Mammalian target of rapamycin (mTOR) inhibitors are used as potent
      immunosuppressive agents in solid-organ transplant recipients (everolimus and
      sirolimus) and as antineoplastic therapies for various cancers (eg, advanced
      renal cell carcinoma; everolimus, temsirolimus, ridaforolimus). Relevant
      literature, obtained from specific PubMed searches, was reviewed to evaluate the
      incidence and mechanistic features of specific adverse events (AEs) associated
      with mTOR inhibitor treatment, and to present strategies to effectively manage
      these events. The AEs examined in this review include stomatitis and other
      cutaneous AEs, wound-healing complications (eg, lymphocele, incisional hernia),
      diabetes/hyperglycemia, dyslipidemia, proteinuria, nephrotoxicity, delayed graft
      function, pneumonitis, anemia, hypertension, gonadal dysfunction, and ovarian
      toxicity. Strategies for selecting appropriate patients for mTOR inhibitor
      therapy and minimizing the risks of AEs are discussed, along with best practices
      for identifying and managing side effects. mTOR inhibitors are promising
      therapeutic options in immunosuppression and oncology; most AEs can be
      effectively detected and managed or reversed with careful monitoring and
      appropriate interventions.

PMID- 24685371
TI  - [One-lung ventilation in a patient with a tracheal bronchus].
AB  - We report a patient in whom a tracheal bronchus was discovered intraoperatively
      during an endoscopy control. This observation led us to a focus on what to do in
      such cases. 

PMID- 24685372
TI  - Adverse events following rabies post-exposure prophylaxis: a comparative study of
      two different schedules and two vaccines.
AB  - OBJECTIVE: Due to lack of effective treatment for rabies, post-exposure
      prophylaxis becomes very important. In this study, we investigated side effects
      developed in patients following administration of rabies post-exposure
      prophylaxis. METHODS: A total of 1685 patients were vaccinated. 265 patients
      (15.7%) administered the Essen regimen with equine rabies immunoglobulin and 1420
      patients (84.2%) administered Zagreb regimen. 761 (45.2%) patients were
      vaccinated with a verocell vaccine; Verorab and 924 patients (54.8%) were
      vaccinated with Abhayrab. RESULTS: All side effects were higher in female
      patients than those of males. The patients with chronic illness also had
      significantly, increased side effects; headache (12.4%), pain at site of
      administration (11.3%), and arthralgia (10.5%) compared to the patients without
      chronic illness. We grouped the patients in three as; 0-15 years, 15-60 years,
      and 60 years and above. In the first group; fever (21.2%), vomiting (2.4%) and
      coughing (2.1%); in the second group (15-60 years), headache (8.8%), arthralgia
      (6.7%) were significantly increased compared to the other groups. Side effects
      are significantly higher with schema of 2-1-1 and Abhayrab trade mark vaccine,
      particularly following the first doses. DISCUSSION: Second generation rabies
      vaccines are safe, effective and cheaper than HDCV. When fatality of rabies
      disease is considered, occurring side effects can be tolerated.

PMID- 24685373
TI  - Is there a legal framework for action towards travelers' health in Latin America?

PMID- 24685374
TI  - Hybrid versus Norwood procedure for hypoplastic left heart syndrome: contemporary
      series from a single center.
AB  - OBJECTIVE: Two different strategies have emerged in the initial palliation for
      hypoplastic left heart syndrome, the conventional Norwood operation and the so
      called hybrid procedure. We have used each of these at our center. The purpose of
      the present study was to compare the outcomes of both procedures. METHODS: From
      2007 to 2012, 40 patients presented to the Cardinal Glennon Children's Medical
      Center with hypoplastic left heart syndrome or 1 of its variants. Of the 40
      patients, 24 underwent a hybrid procedure and 16 a Norwood procedure for initial
      palliation. The medical records, echocardiograms, and cardiac catheterization
      data were retrospectively reviewed. Standard statistical analysis was performed.
      RESULTS: The patients who underwent the hybrid procedure weighed less than those
      who underwent the Norwood procedure. Overall unadjusted survival was better in
      the Norwood group, although this did not reach statistical significance. Overall
      hospital resource usage was similar in both cohorts, taking into account both
      first and second palliation stages. CONCLUSIONS: In our review, we found no
      statistically significant difference in survival or resource usage between those
      patients undergoing the Norwood procedure and those undergoing a hybrid procedure
      as initial palliation for hypoplastic left heart syndrome.

PMID- 24685375
TI  - Global experience with an inner branched arch endograft.
AB  - BACKGROUND: Branched endografts are a new option to treat arch aneurysm in high
      risk patients. METHODS AND RESULTS: We performed a retrospective multicenter
      analysis of all patients with arch aneurysms treated with a new branched
      endograft designed with 2 inner branches to perfuse the supra aortic trunks.
      Thirty-eight patients were included. The median age was 71 years (range, 64-74
      years). An American Society of Anesthesiologists score of 3 or 4 was reported in
      89.5% (95% confidence interval [CI], 79.7-99.3) of patients. The 30-day mortality
      rate was 13.2% (95% CI, 2.2-24.2). Technical success was obtained in 32 patients
      (84.2% [95% CI, 72.4-95.9]). Early secondary procedures were performed in 4
      patients (10.5% [95% CI, 0.7-20.3]). Early cerebrovascular complications were
      diagnosed in 6 patients (15.8% [95% CI, 4.0-27.6]), including 4 transient
      ischemic attacks, 1 stroke, and 1 subarachnoid hemorrhage. The median follow-up
      was 12 months (range, 6-12 months). During follow-up, no aneurysm-related death
      was detected. Secondary procedures during follow-up were performed in 3 patients
      (9.1% [95% CI, 0.0-19.1]), including 1 conversion to open surgery. We compared
      the first 10 patients (early experience group) with the subsequent 28 patients.
      Intraoperative complications and secondary procedures were significantly higher
      in the early experience group. Although not statistically significant, the early
      mortality was higher in the early experience group (30% [95% CI, 0.0-60.0])
      versus the remainder (7.1% [95% CI, 0.0-16.9]; P=.066). Being part of the early
      experience group and ascending aortic diameter>=38 mm were found to be associated
      to higher rates of combined early mortality and neurologic complications.
      CONCLUSIONS: Our preliminary study confirms the feasibility and safety of the
      endovascular repair of arch aneurysms in selected patients who may not have other
      conventional options. CLINICAL TRIAL REGISTRATION INFORMATION: Thoracic IDE
      NCT00583817, FDA IDE# 000101.

PMID- 24685376
TI  - Long-term results of Freestyle stentless bioprosthesis in the aortic position: a
      single-center prospective cohort of 500 patients.
AB  - OBJECTIVE: Stentless xenograft bioprostheses may be the future valve of choice
      for aortic valve replacement. The study aim was to investigate the long-term
      clinical outcome after aortic valve replacement with the Medtronic Freestyle
      bioprosthesis (Medtronic Inc, Minneapolis, Minn). METHODS: Between April 1997 and
      November 2004, a total of 500 patients (mean age, 74.5+/-9.6 years; 52% were
      male) underwent aortic valve replacement with a Freestyle bioprosthesis, without
      population selection. The surgical procedure used a modified subcoronary
      technique in 479 patients and a complete root replacement in 21 patients,
      conducted with mini-extracorporeal circulation. Concomitant procedures included
      coronary artery bypass grafting in 122 patients (24%) and mitral valve
      repair/replacement in 11 patients. RESULTS: The mean cardiopulmonary bypass time
      was 98+/-26 minutes, and total aortic crossclamp time was 77+/-19 minutes.
      Operative mortality was 5.2%. The median follow-up time was 104.8+/-5.7 months.
      During this period, there were 224 deaths (n=122 cardiovascular and n=102
      noncardiovascular deaths). The actuarial survivals from cardiovascular and valve
      related mortality were 67%+/-3% and 70%+/-4%, respectively, at 10 years. Freedom
      from structural valve deterioration at 10 years was 94%+/-2%. The linearized
      structural valve deterioration incidence was 0.6% per patient/year. Multivariate
      Cox regression analysis revealed that older age, impaired renal function, and
      coronary artery disease were independent predictors of cardiovascular death. In
      the subgroup of patients aged less than 65 years at implantation (n=45), the
      actuarial cardiovascular survival was 83%+/-8% and freedom from structural valve
      deterioration was 89%+/-6% at 10 years. CONCLUSIONS: The use of the Freestyle
      bioprosthesis for aortic valve replacement resulted in good long-term
      cardiovascular survival and freedom from structural valve deterioration in this
      cohort regardless of age at implantation.

PMID- 24685377
TI  - A new technique for venous unifocalization of the bilateral superior vena cava
      with the Glenn procedure.

PMID- 24685378
TI  - Blood lactate level during extracorporeal life support as a surrogate marker for
      survival.
AB  - OBJECTIVE: The establishment of reliable markers to monitor adequate tissue
      perfusion during extracorporeal life support is clinically important to improve
      outcomes. METHODS: We evaluated 115 consecutive adult patients (aged 61.7 +/-
      13.4 years, 59 female patients) undergoing extracorporeal life support to manage
      low cardiac output syndrome after major cardiac surgery. The blood lactate levels
      serially measured during extracorporeal life support (at 6, 12, and 24 hours)
      were analyzed. RESULTS: Forty-seven patients (40.8%) were weaned off
      extracorporeal life support successfully, and 32 patients (27.8%) survived to
      discharge. On logistic regression analysis, a high blood lactate level before
      extracorporeal life support (relative risk [RR], 1.19; 95% confidence interval
      [CI], 1.06-1.34) and cardiopulmonary bypass weaning failure after surgery (RR,
      4.39; 95% CI, 1.44-13.35) emerged as baseline risk factors of mortality. After
      adjustment with these factors, blood lactate levels at 6 hours (RR, 1.24; 95% CI,
      1.06-1.46), 12 hours (RR, 1.35; 95% CI, 1.10-1.67), and 24 hours (RR, 1.46; 95%
      CI, 1.10-1.93) were predictive of mortality. When the predictive values of serial
      blood lactate levels for mortality were assessed using the receiver operating
      characteristic method, the greatest accuracy was obtained at cutoff values of
      7.05 mmol/L at 6 hours (sensitivity, 75.5%; specificity, 75.0%), 4.95 mmol/L at
      12 hours (sensitivity, 70.4%; specificity, 76%), and 4.15 mmol/L at 24 hours
      (sensitivity, 62%; specificity, 93.1%). CONCLUSIONS: Blood lactate measurement
      can be used as a reliable tool for monitoring adequate tissue perfusion during
      extracorporeal life support and was strongly predictive of mortality. Therefore,
      in patients without adequate decrement in lactate levels during extracorporeal
      life support, potential factors responsible for inadequate perfusion should be
      identified and corrected.

PMID- 24685380
TI  - New approach to implantable cardioverter-defibrillators in small pediatric
      patients: dorsal positioning of superior vena cava shock lead in a 3-year-old.

PMID- 24685379
TI  - Five-year real world outcomes of GeoForm ring implantation in patients with
      ischemic mitral regurgitation.
AB  - BACKGROUND: Reductive ring annuloplasty represents the current standard surgical
      therapy for ischemic mitral regurgitation (IMR); however, the clinical results
      have been suboptimal. Etiology-specific prostheses such as the GeoForm
      annuloplasty ring have been designed to better address the annular and
      subvalvular perturbations associated with IMR. However, clinical experience is
      limited, and mid-term results are lacking. METHODS: We reviewed the clinical
      outcomes of 86 patients who had undergone implantation of a GeoForm ring at our
      center from 2005 to 2011. Perioperative mortality and clinical parameters were
      derived from The Society of Thoracic Surgeons database. Follow-up survival was
      assessed using the Social Security Death Index. Surviving patients were
      interviewed by telephone for valve-specific follow-up data and to complete the
      Medical Outcomes Study, short-form, 36-item, quality-of-life questionnaire.
      RESULTS: The mean grade of IMR preoperatively was 3.1+/-0.8 (range, 1-4+), 0.2+/
      0.4 in the immediate postoperative period, and 0.7+/-0.7 at the last mean follow
      up point of 41 months; only 2 patients developed >=2+IMR during the follow-up
      period, for a 5-year freedom from recurrent 2+ IMR of 86%. The mean left
      ventricular end-diastolic and end-systolic diameters decreased from before to
      after surgery from 6.0+/-0.0 cm to 5.3+/-09 cm and 5.0+/-0.9 cm to 4.3+/-1.1 cm,
      respectively (P<.001). Perioperative mortality was 5.8% (5 of 86), and 1-, 3-,
      and 5-year survival was 87%, 81%, and 75%, respectively. At the last follow-up
      point, 80% of patients were in New York Heart Association class I and II, and
      their quality of life was equal to, or better than, age-matched controls from the
      general population. CONCLUSIONS: Implantation of the GeoForm ring offers very
      good control of IMR, with low rate of recurrent IMR at mid-term follow-up. The
      use of this prosthesis was associated with good perioperative mortality, mid-term
      survival, and quality of life.

PMID- 24685381
TI  - Pretransplant serum human chitinase-like glycoprotein YKL-40 concentrations
      independently predict bronchiolitis obliterans development in lung transplant
      recipients.
AB  - OBJECTIVE: Bronchiolitis obliterans syndrome (BOS) is the main long-term
      complication limiting survival after lung transplantation. There exists no cure
      for BOS and its mechanisms are not well understood. Early identification of BOS
      could therefore contribute to improvement of therapeutic and preventive measures.
      The human chitinase-like glycoprotein YKL-40 is involved in regulation of
      inflammatory tissue response and remodeling and is associated with pulmonary
      fibrosis. However, its role in BOS is unknown. METHODS: A total of 57 recipients
      with irreversible fibrotic BOS and matched 85 recipients without BOS were
      retrospectively analyzed. Pretransplant serum samples were available at the time
      of the study. Serum and bronchoalveolar lavage samples were obtained at BOS
      diagnosis or at a comparable time point in patients without BOS. Additionally,
      serum samples were obtained 3 months later after BOS diagnosis or after the first
      sample in patients without BOS. YKL-40 concentrations were analyzed by enzyme
      linked immunosorbent assay. RESULTS: Pretransplant serum YKL-40 concentrations
      were higher in recipients who developed BOS and were useful in identifying
      patients at high risk for BOS development (odds ratio, 1.3; 95% confidence
      interval, 1.01-1.9; P = .02). At BOS diagnosis, posttransplant YKL-40
      concentrations were significantly elevated in the serum and bronchoalveolar
      lavage of patients with BOS compared with those without BOS at a comparable
      posttransplant time point. Of note, there was no significant association between
      serum YKL-40 concentrations and the frequency of acute rejection episodes.
      CONCLUSIONS: Elevated pretransplant serum YKL-40 concentration is associated with
      BOS development and could be an independent biomarker in early prediction and
      monitoring of BOS.

PMID- 24685382
TI  - Editorial comment.

PMID- 24685384
TI  - Simulation of probe position-dependent electron energy-loss fine structure.
AB  - We present a theoretical framework for calculating probe-position-dependent
      electron energy-loss near-edge structure for the scanning transmission electron
      microscope by combining density functional theory with dynamical scattering
      theory. We show how simpler approaches to calculating near-edge structure fail to
      include the fundamental physics needed to understand the evolution of near-edge
      structure as a function of probe position and investigate the dependence of near
      edge structure on probe size. It is within this framework that density functional
      theory should be presented, in order to ensure that variations of near-edge
      structure are truly due to local electronic structure and how much from the
      diffraction and focusing of the electron beam. 

PMID- 24685383
TI  - Rapid effects of estrogens on behavior: environmental modulation and molecular
      mechanisms.
AB  - Estradiol can modulate neural activity and behavior via both genomic and
      nongenomic mechanisms. Environmental cues have a major impact on the relative
      importance of these signaling pathways with significant consequences for
      behavior. First we consider how photoperiod modulates nongenomic estrogen
      signaling on behavior. Intriguingly, short days permit rapid effects of estrogens
      on aggression in both rodents and song sparrows. This highlights the importance
      of considering photoperiod as a variable in laboratory research. Next we review
      evidence for rapid effects of estradiol on ecologically-relevant behaviors
      including aggression, copulation, communication, and learning. We also address
      the impact of endocrine disruptors on estrogen signaling, such as those found in
      corncob bedding used in rodent research. Finally, we examine the biochemical
      mechanisms that may mediate rapid estrogen action on behavior in males and
      females. A common theme across these topics is that the effects of estrogens on
      social behaviors vary across different environmental conditions. 

PMID- 24685385
TI  - Factors associated with home discharge among veterans with stroke.
AB  - OBJECTIVE: To determine which patient-, treatment-, and facility-level
      characteristics were associated with home discharge among patients hospitalized
      for stroke within the Department of Veterans Affairs. DESIGN: Retrospective
      observational study. SETTING: Veterans Affairs facilities nationwide.
      PARTICIPANTS: Veterans hospitalized for stroke during fiscal year 2007 to fiscal
      year 2008 (N=12,565). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE:
      Discharge location after hospitalization. RESULTS: There were 10,130 (80.6%)
      veterans discharged home after hospitalization for acute stroke. Married veterans
      were more likely than nonmarried veterans to be discharged home (odds ratio
      [OR]=1.23; 95% confidence interval [CI]=1.11-1.35). Compared with veterans
      admitted to the hospital from home, patients admitted from extended care were
      less likely to be discharged home (OR=.04; 95% CI=.03-.07). Compared with those
      with occlusion of cerebral arteries, patients with intracerebral hemorrhage
      (OR=.61; 95% CI=.50-.74) or other central nervous system hemorrhage (OR=.78; 95%
      CI=.63-.96) were less likely to be discharged home, whereas patients with
      occlusion of precerebral arteries (OR=1.36; 95% CI=1.07-1.73) were more likely to
      return home. Evidence of congestive heart failure (OR=.85; 95% CI=.76-.95), fluid
      and electrolyte disorders (OR=.86; 95% CI=.77-.96), internal organ procedures and
      diagnostics (OR=.87; 95% CI=.78-.97), and serious nutritional compromise (OR=.49;
      95% CI=.40-.62) during hospitalization remained independently associated with
      lower odds of home discharge. Longer hospitalizations and receipt of
      rehabilitation services while hospitalized acutely were negatively associated,
      whereas treatment on more bed sections and rehabilitation accreditation of the
      facility were positively associated with home discharge. Region exerted a
      statistically significant effect on home discharge. CONCLUSIONS: We found
      sociological, clinical, and facility-level factors associated with home discharge
      after hospitalization for acute stroke. Findings document the importance of
      considering a broad range of characteristics rather than focusing only on a few
      specific traits during discharge planning.

PMID- 24685386
TI  - Assisted movement with proprioceptive stimulation reduces impairment and restores
      function in incomplete spinal cord injury.
AB  - OBJECTIVE: To test whether treatment with assisted movement with enhanced
      sensation (AMES) using vibration to the antagonist muscle would reduce
      impairments and restore upper limb function in people with incomplete
      tetraplegia. DESIGN: Prospective, pre-post study. SETTING: Laboratory and
      rehabilitation hospital. PARTICIPANTS: We recruited 15 arms from 10 individuals
      (8 men; mean age, 40.5 y; mean years postspinal cord injury [SCI], 3) with
      chronic, incomplete tetraplegia. INTERVENTION: Two or three 20-minute sessions
      per week over 9 to 13 weeks (25 sessions total) on the AMES device, which
      combines repeated movement with targeted vibration to the antagonist muscle. MAIN
      OUTCOME MEASURES: Strength and active motion tests on the AMES device;
      International Standards for the Neurological Classification of SCI (ISNCSCI)
      motor and sensory examinations; Modified Ashworth Scale (MAS); grasp and release
      test (GRT); Van Lieshout Test (VLT); and Capabilities of Upper Extremity
      questionnaire (CUE). RESULTS: The AMES strength test scores improved
      significantly in metacarpophalangeal flexion (P=.024) and extension (P=.007) and
      wrist flexion (P=.001) and extension (P<.000). The AMES active motion scores
      improved in the hand (P=.001) and wrist (P=.001). The MAS and ISNCSCI scores
      remained unchanged, whereas the GRT scores increased (P=.025). Post hoc analysis
      showed a trend from pre- to posttreatment (P=.068) and a significant change from
      pretreatment to 3-month follow-up (P=.046). There was no significant change in
      the VLT (P=.951) or the CUE (P=.164). Five of the 10 participants reported a
      return of sensation to the digits after the first, second, or third treatment
      session. CONCLUSIONS: People with chronic, incomplete tetraplegia may experience
      improvements in impairments and function after treatment on a device combining
      assisted movement and proprioceptive stimulation. Further investigation is
      warranted.

PMID- 24685387
TI  - Heterotopic ossification in civilians with lower limb amputations.
AB  - OBJECTIVES: To report the incidence of symptomatic heterotopic ossification (HO)
      in a defined civilian amputee population, describe its characteristics, and
      compare these findings to published data in military amputees. DESIGN:
      Retrospective chart analysis from July 1998 to July 2009. SETTING: Ambulatory
      amputee clinic within a large university medical center. PARTICIPANTS: Adults
      with lower limb amputation (N=158). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Patients with symptomatic HO confirmed by radiographs. RESULTS: A total
      of 261 patients were evaluated; 158 met inclusion criteria, with 59% having
      traumatic etiology, 18% vascular etiology, 22% infection, and 1% tumor.
      Symptomatic HO was diagnosed in 36 (22.8%) patients, and 94% patients had mild HO
      on radiographic scoring. Rate of HO in amputations related to trauma was not
      increased compared with those of other etiologies. Surgical resection of the
      ectopic bone was required in 4 (11%) patients. CONCLUSIONS: HO is seen commonly
      after civilian lower limb amputation regardless of etiology. The prevalence was
      less than that observed in previous reports from military populations. This is
      the first report estimating the prevalence of HO in adult civilian amputees.

PMID- 24685388
TI  - Computer-adaptive balance testing improves discrimination between community
      dwelling elderly fallers and nonfallers.
AB  - OBJECTIVES: To build an item response theory-based computer adaptive test (CAT)
      for balance from 3 traditional, fixed-form balance measures: Berg Balance Scale
      (BBS), Performance-Oriented Mobility Assessment (POMA), and dynamic gait index
      (DGI); and to examine whether the CAT's psychometric performance exceeded that of
      individual measures. DESIGN: Secondary analysis combining 2 existing datasets.
      SETTING: Community based. PARTICIPANTS: Community-dwelling older adults (N=187)
      who were aged >=65 years (mean age, 75.2+/-6.8y, 69% women). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The BBS, POMA, and DGI items were compiled
      into an initial 38-item bank. The Rasch partial credit model was used for final
      item bank calibration. CAT simulations were conducted to identify the ideal CAT.
      CAT score accuracy, reliability, floor and ceiling effects, and validity were
      examined. Floor and ceiling effects and validity of the CAT and individual
      measures were compared. RESULTS: A 23-item bank met model expectations. A 10-item
      CAT was selected, showing a very strong association with full item bank scores
      (r=.97) and good overall reliability (.78). Reliability was better in low- to
      midbalance ranges as a result of better item targeting to balance ability when
      compared with the highest balance ranges. No floor effect was noted. The CAT
      ceiling effect (11.2%) was significantly lower than the POMA (40.1%) and DGI
      (40.3%) ceiling effects (P<.001 per comparison). The CAT outperformed individual
      measures, being the only test to discriminate between fallers and nonfallers
      (P=.007), and being the strongest predictor of self-reported function.
      CONCLUSIONS: The balance CAT showed excellent accuracy, good overall reliability,
      and excellent validity compared with individual measures, being the only measure
      to discriminate between fallers and nonfallers. Prospective examination,
      particularly in low-functioning older adults and clinical populations with
      balance deficits, is recommended. Development of an improved CAT based on an
      expanded item bank containing higher difficulty items is also recommended.

PMID- 24685389
TI  - Randomized controlled trial of the effectiveness of continuous passive motion
      after total knee replacement.
AB  - OBJECTIVE: To determine the effects of using a continuous passive motion (CPM)
      device for individuals with poor range of motion (ROM) after a total knee
      replacement (TKR) admitted for postacute rehabilitation. DESIGN: Randomized
      controlled trial. SETTING: Inpatient rehabilitation facility (IRF). PARTICIPANTS:
      Adults (N=141) after TKR with initial active knee flexion <75 degrees  on
      admission to the IRF. INTERVENTION: Two randomized groups: group 1 (n=71)
      received the conventional 3 hours of therapy per day, and group 2 (n=70) received
      the addition of daily CPM use for 2 hours throughout their length of stay. MAIN
      OUTCOME MEASURES: The primary outcome measure was active knee flexion ROM.
      Secondary outcome measures included active knee extension ROM length of stay,
      estimate of function using the FIM and Timed Up and Go test, girth measurement,
      and self-reported Western Ontario and McMaster Universities Osteoarthritis Index
      scores. RESULTS: All subjects significantly improved from admission to discharge
      in all outcome measures. However, there were no statistically significant
      differences in any of the discharge outcome measures of the CPM group compared
      with the non-CPM group. CONCLUSIONS: CPM does not provide an additional benefit
      over the conventional interventions used in an IRF for patient after TKR,
      specifically in patients with poor initial knee flexion ROM after surgery.

PMID- 24685390
TI  - Influence of left- and right-side total hip arthroplasty on the ability to
      perform an emergency stop while driving a car.
AB  - OBJECTIVE: To show the possible effect of left- and right-side total hip
      arthroplasty (THA) on the ability to perform an emergency stop when driving a
      car. DESIGN: Inception cohort. SETTING: A driving simulator using an actual car
      cabin, specifically developed for the experiment, was used for testing driving
      ability. PARTICIPANTS: Patients (N=40; 20 left-side THA/20 right-side THA) were
      tested preoperatively and in increments of 8 days and 6, 12, and 52 weeks after
      surgery. INTERVENTIONS: Left- and right-side THA. MAIN OUTCOME MEASURES: Reaction
      time, movement time, total brake response time (TBRT), and maximum brake force.
      RESULTS: Eight days postoperatively, measurements on driving performance
      indicated a slight worsening for all outcome parameters in patients after left
      side THA and considerably more worsening in patients after right-side THA. For
      both patient groups, significant improvements in outcome measures were noted
      during the 1-year follow-up. Brake force declined significantly in patients with
      left-side THA (P=.012) and in patients after right-side THA (P<.001). A total of
      35% of the patients with right-side THA and 15% with left-side THA could not meet
      the 600 ms TBRT threshold 6 weeks postoperatively. CONCLUSIONS: Most patients who
      underwent right-side THA reached their preoperative baseline 6 weeks after
      surgery. Most of the patients with left-side THA showed no TBRT limitations 8
      days postoperatively. Because of the patients' highly individual rehabilitation
      course and considering the possible consequences of the premature resumption of
      driving a motor vehicle, individual examination and recommendation are necessary.

PMID- 24685391
TI  - Engineering the Caenorhabditis elegans genome with CRISPR/Cas9.
AB  - The development in early 2013 of CRISPR/Cas9-based genome engineering promises to
      dramatically advance our ability to alter the genomes of model systems at will. A
      single, easily produced targeting RNA guides the Cas9 endonuclease to a specific
      DNA sequence where it creates a double strand break. Imprecise repair of the
      break can yield mutations, while homologous recombination with a repair template
      can be used to effect specific changes to the genome. The tremendous potential of
      this system led several groups to independently adapt it for use in
      Caenorhabditiselegans, where it was successfully used to generate mutations and
      to create tailored genome changes through homologous recombination. Here, we
      review the different approaches taken to adapt CRISPR/Cas9 for C. elegans, and
      provide practical guidelines for CRISPR/Cas9-based genome engineering. 

PMID- 24685392
TI  - Tools and methods for studying the Drosophila JAK/STAT pathway.
AB  - The Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT)
      signaling pathway is one of a limited number of signaling cascades that is
      extensively utilized for many developmental and homeostatic functions. The
      JAK/STAT pathway is evolutionarily conserved from insects to mammals, with
      homologous transduction machinery in each. Yet the mammalian pathway is composed
      of multiple members for each family of proteins, while flies have only a single
      homologue of most pathway components. This simplicity and the abundance of
      genetic, biochemical, and developmental tools make Drosophila an attractive model
      to investigate this important signaling pathway. This review provides a basic
      description of the Drosophila JAK/STAT cascade and summarizes currently available
      reagents and tools to study and manipulate the pathway. 

PMID- 24685393
TI  - Good syndrome and polymyositis.

PMID- 24685395
TI  - Future directions for worksite cardiovascular risk factor reduction programs to
      reduce health disparities.

PMID- 24685394
TI  - Pulmonary rehabilitation improves heart rate variability at peak exercise,
      exercise capacity and health-related quality of life in chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) appear to
      have impaired cardiac autonomic modulation with depressed heart rate variability
      (HRV). Pulmonary rehabilitation (PR) is recommended as an integral part of the
      management. However, the effect of PR on HRV at peak exercise remains unclear.
      METHODS: Sixty-four patients with COPD participated in a 12-week, 2 sessions-per
      week, hospital-based PR program. Baseline and post-PR status were evaluated by
      spirometry, HRV, health-related quality of life (HRQL, St. George's Respiratory
      Questionnaire, SGRQ), cardiopulmonary exercise test, respiratory muscle strength,
      and dyspnea Borg's scale. RESULTS: After PR, there were significant improvements
      in the time and frequency domains of HRV with increased standard deviation of the
      normal R-R intervals, difference between adjacent normal R-R intervals within a
      given time minus one, high-frequency and decreased low-frequency, as well as
      concurrent improvements in HRQL, exercise capacity, dyspnea score, and
      respiratory muscle strength (all p < 0.05). CONCLUSIONS: PR results in
      significant improvements in autonomic function, with concurrent improvements in
      HRQL and exercise capacity.

PMID- 24685396
TI  - Insomnia research: 3Ps and beyond.

PMID- 24685397
TI  - A guide into glycosciences: How chemistry, biochemistry and biology cooperate to
      crack the sugar code.
AB  - BACKGROUND: The most demanding challenge in research on molecular aspects within
      the flow of biological information is posed by the complex carbohydrates (glycan
      part of cellular glycoconjugates). How the 'message' encoded in carbohydrate
      'letters' is 'read' and 'translated' can only be unraveled by interdisciplinary
      efforts. SCOPE OF REVIEW: This review provides a didactic step-by-step survey of
      the concept of the sugar code and the way strategic combination of experimental
      approaches characterizes structure-function relationships, with resources for
      teaching. MAJOR CONCLUSIONS: The unsurpassed coding capacity of glycans is an
      ideal platform for generating a broad range of molecular 'messages'. Structural
      and functional analyses of complex carbohydrates have been made possible by
      advances in chemical synthesis, rendering production of oligosaccharides,
      glycoclusters and neoglycoconjugates possible. This availability facilitates to
      test the glycans as ligands for natural sugar receptors (lectins). Their
      interaction is a means to turn sugar-encoded information into cellular effects.
      Glycan/lectin structures and their spatial modes of presentation underlie the
      exquisite specificity of the endogenous lectins in counterreceptor selection,
      that is, to home in on certain cellular glycoproteins or glycolipids. GENERAL
      SIGNIFICANCE: Understanding how sugar-encoded 'messages' are 'read' and
      'translated' by lectins provides insights into fundamental mechanisms of life,
      with potential for medical applications.

PMID- 24685398
TI  - [Design of a program for the positive development of schoolchildren and
      characteristics of participants (Medellin, Colombia)].
AB  - The design of the program for the promotion of personal potential and prevention
      of risky health behaviors in school-aged children, PILAS! Better Adults, Better
      Kids, was based on local and international evidence on programs for the
      prevention of school-based violence. The program offers a training process for
      parents and teachers through active methodologies and advice (provided for 10
      months) based on topics that encourage individual child development and the
      delegitimization of violence in everyday interactions. A total of 306 teachers,
      800 parents and 12,800 children benefited from the program. An initial
      measurement was conducted using a scale ranging from 0 to 100 in a sample of 1751
      children. The results showed an average of 80 in the children's social skills,
      but caregivers reported high levels of aggression. Communication and supervision
      failures were found among parents, as well as punishment practices through
      psychological and physical aggression. Another finding was low social cohesion in
      the neighborhood.

PMID- 24685399
TI  - Economic benefits from food recovery at the retail stage: an application to
      Italian food chains.
AB  - The food supply chain is affected by losses of products near to their expiry date
      or damaged by improper transportation or production defects. Such products are
      usually poorly attractive for the consumer in the target market even if they
      maintain their nutritional properties. On the other hand undernourished people
      face every day the problem of fulfilling their nutritional needs usually relying
      on non-profit organizations. In this field the food recovery enabling economic
      benefits for donors is nowadays seen as a coherent way to manage food products
      unsalable in the target market for various causes and thus destined to be
      discarded and disposed to landfill thus representing only a cost. Despite its
      obvious affordability the food recovery is today not always practiced because the
      economic benefits that could be achieved are barely known. The paper aims at
      presenting a deterministic mathematical model for the optimization of the supply
      chain composed by retailers and potential recipients that practice the food
      recovery, taking into account the benefits recognized to donors and the
      management costs of the food recovery. The model determines the optimal time to
      withdraw the products from the shelves as well as the quantities to be donated to
      the non-profit organizations and those to be sent to the livestock market
      maximizing the retailer profit. The results show that the optimal conditions
      ensuring the affordability of the food recovery strategy including the tax
      reliefs and cost saving for the retailers outperforms the profit achievable in
      absence of such a system. 

PMID- 24685400
TI  - Metal toxicity assessment of mobile phone parts using Milli Q water.
AB  - Environmentally safe disposal of end-of-life (EoL) or discarded mobile phone is a
      serious problem on account of their ever increasing number and toxic metals
      contents. In the present work, metal toxicity of mobile phone plastics, printed
      wire boards (PWBs) and batteries were assessed through dynamic batch leaching
      using Milli Q (MQ) water. Phone plastics failed Toxicity Characterization
      Leaching Procedure (TCLP) and Waste Extraction Test (WET) for Pb as the
      cumulative amount of Pb leached from plastics (5.33 mg/l) exceeded the regulatory
      limits (5.0mg/l) used in characterizing a waste as hazardous. Similarly, the
      average cumulative amount (21.83 mg/l) of Ni leached from PWBs exceeded the
      regulatory limit of 20mg/l and thus PWBs failed WET. Metals leached from
      batteries in small amounts (Cr: 0.40 mg/l and Ni: 0.15 mg/l). The presence of Fe
      in the batteries and its precipitation as oxides/hydroxides in the leaching
      solution hindered the leaching of other metals in MQ water. Both plastics and
      PWBs should be treated as hazardous waste and should not be disposed in open
      landfills. Further, MQ water leaching could provide good simulation of metals
      leaching from the mobile phones disposed at landfill sites.

PMID- 24685401
TI  - Septin 7 immunoexpression in papillary thyroid carcinoma: a preliminary study.
AB  - Papillary thyroid carcinoma (PTC) is the most common type among thyroid cancers.
      The diagnosis of PTC may be challenging when follicular variant (FVPTC) of this
      disease is present due to the resemblance of nuclear properties of the classical
      type (CVPTC). However, making use of ancillary molecular markers in the diagnosis
      of PTC may help. In our study, we aimed to evaluate the SEPT7 protein expression
      in PTC. A total of 55 paraffin block tissue samples comprising encapsulated FVPTC
      (FVPTC(e), n=25), and CVPTC (n=15), and benign hyperfunctioning thyroid nodules
      (HypN, n=15) were used in this study. Nuclear, cytoplasmic, and overall (total)
      SEPT7 protein expression levels were determined by using immunohistochemistry.
      Nuclear, cytoplasmic, and overall SEPT7 expressions (p=0.02, p=0.001, p=0.002,
      respectively) were significantly lower in FVPTC(e) tissues when compared to HypN.
      In CVPTC group, nuclear expression was significantly lower (p=0.004) while
      overall and cytoplasmic expressions were not changed (p>0.05). In HypN group,
      highest nuclear (mean=2.73), cytoplasmic (mean=2.86), and overall (mean=2.86)
      expression scores were detected. Significantly lower SEPT7 expression in all
      expressional categories in FVPTC(e) group may be a sign of different molecular
      signature in this type of tissue. 

PMID- 24685402
TI  - Extensive facial hematoma following third molar removal.

PMID- 24685403
TI  - beta-adrenoceptors as molecular targets in the treatment of hypertension.
AB  - Regulation of sympathoadrenal activity has been a long-time target in the
      management of hypertension. Regulation of beta-adrenoceptor (betaAR) function has
      been the most therapeutically important of these targets. The development of
      effective antihypertensive treatments based on betaAR antagonism paralleled the
      elucidation of the molecular basis of beta-adrenergic effects by the family of
      betaARs, which are members of the G-protein-coupled receptor (GPCR) superfamily.
      betaARs serve as the extracellular face of the transmembrane signalling pathway
      that results in the consequent activation of heterotrimeric G-proteins and the
      activation of several other newly appreciated signalling molecules that include
      beta-arrestins and GPCR kinases (GRKs). The aggregate effect of the activation of
      these signalling pathways mediates the response to betaAR activation.
      Paradoxically, the hypertensive state is characterized by impaired betaAR
      responsiveness. This defect is common to many other receptor systems linked to
      the stimulator G protein (Gs) and adenylyl cyclase activation. This impairment is
      principally mediated by receptor-G-protein uncoupling, which has been linked to
      increased expression and activity of GRK2. 

PMID- 24685404
TI  - CareHPV cervical cancer screening demonstration in a rural population of north
      India.
AB  - OBJECTIVE: To compare cervical careHPV screening in a rural community setting
      with other methods of cervical screening for the detection of high-grade cervical
      intra-epithelial neoplasia (CIN). STUDY DESIGN: Cross-sectional study. All ever
      married women aged 30-59 years surveyed in an administrative area of Uttar
      Pradesh, India were targeted for screening by careHPV (cervical and vaginal
      samples), Pap test and visual inspection of the cervix following application of
      acetic acid (VIA). Women who screened positive were referred for colposcopy and
      the results were confirmed histologically. Sensitivity, specificity and
      predictive values for the detection of histological CINII+ and CINIII+ were
      assessed for each screening test. RESULTS: Sixty-five percent (5032/7704) of the
      women invited for cervical screening agreed to participate in the study. Screen
      positive rates for cervical careHPV, vaginal careHPV, Pap test and VIA were 3%,
      2%, 3% and 6%, respectively. Data for women who did not complete all screening
      modes, women lost to follow-up and women with missing histological results were
      excluded before data analysis, resulting in a final sample size of 4658. Cervical
      careHPV had high sensitivity (85%) for the detection of CINIII+ lesions and
      moderate sensitivity (53%) for the detection of CINII+ lesions. Sensitivities for
      the detection of CINIII+ and CINII+ were 54% and 41% for vaginal careHPV, 62% and
      44% for Pap test, and 8% and 22% for VIA, respectively. CONCLUSION: Cervical
      careHPV testing is superior to VIA and Pap test for the detection of high-grade
      CIN in a rural community setting.

PMID- 24685406
TI  - Patient-related factors associated with depressive state in caregivers of
      patients with dementia at home.
AB  - OBJECTVES: To identify patient-related factors associated with depressive state
      in caregivers of patients with dementia, we investigated the caregivers' and
      patients' characteristics in relation to the depressive state in their
      caregivers. DESIGN: Prospective hospital-based cohort study. SETTING: Two memory
      clinics in Japan. PARTICIPANTS: Outpatients with dementia (n = 135) and their
      caregivers at home. MEASUREMENTS: The outpatients and their caregivers were
      divided into 2 groups according to the Center for Epidemiologic Studies
      Depression Scale for caregivers. To identify the patient-related factors that
      cause depressive state in caregivers, Mini-Mental State Examination (MMSE), the
      Physical Self-Maintenance Scale for fundamental activities of daily living (ADL),
      and the instrumental ADL scale (IADL) scores for instrumental ADL and the
      neuropsychiatric inventory (NPI) subscale score for behavioral and psychological
      symptoms of dementia were compared between the 2 groups. We used logistic
      regression to determine the independent predictors of caregiver depressive state.
      RESULTS: There was no significant difference in MMSE score between the 2 groups.
      Logistic regression analysis revealed that the depressive state in caregivers was
      related with IADL score and delusion in NPI subscale of patients. CONCLUSIONS:
      Depressive state in caregivers was independent of the decline in cognitive
      function in patients with dementia but was associated with decline in
      instrumental ADL and severity of delusion.

PMID- 24685405
TI  - Inhibition of intimal hyperplasia in murine aortic allografts by the oral
      administration of the transforming growth factor-beta receptor I kinase inhibitor
      SD-208.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) plays a significant role
      in the pathogenesis of the intimal hyperplasia of transplant arteriosclerosis
      (TA). The aim of this study was to evaluate the efficacy of an oral inhibitor of
      TGF-beta receptor I kinase (SD-208) on the development of TA. METHODS: BALB/c (H
      2(d)) donor aortas were transplanted into C57BL/6 (H-2(b)) recipients, and the
      mice then received different doses (40 or 60 mg/kg) of SD-208 or control vehicle
      by daily gavage for 8 weeks. The grafts were analyzed by histology and
      morphometry at 1, 2, 4, 6 and 8 weeks after transplantation. The effects of TGF
      beta and SD-208 on neointimal smooth muscle-like cell (SMLC) and vascular smooth
      muscle cell (VSMC) proliferation and migration were evaluated, and the expression
      levels of Smad3, P-Smad3, connective tissue growth factor (CTGF) and collagen I
      were determined by in vitro experiments. RESULTS: The intimal hyperplasia of the
      SD-208-treated group was significantly reduced compared with the vehicle-treated
      control group (32% and 48% reduction for 40 mg/kg and 60 mg/kg SD-208 compared
      with the controls, respectively [n = 5], p < 0.05). SD-208 reduced SMLC
      proliferation and the production of intimal collagen by 21% and 75%,
      respectively, in the grafts. SD-208 also abolished the promoting effect of TGF
      beta on SMLC proliferation and migration but did not affect TGF-beta inhibition
      of VSMCs in vitro. CTGF, a protein downstream of TGF-beta, was downregulated with
      the inhibition of Smad3 phosphorylation by SD-208, both in vitro and in vivo.
      Moreover, we found that the endogenous Smad3 in SMLCs was upregulated from 2
      weeks after transplantation and was 64% higher than in VSMCs at 8 weeks.
      CONCLUSION: These results demonstrate that SD-208 can effectively reduce the
      formation of intimal hyperplasia of TA in the murine aortic allograft model.

PMID- 24685407
TI  - Dose-responsive effect of psychotropic drug use and subsequent dementia: a
      nationwide propensity score matched case-control study in Taiwan.
AB  - OBJECTIVE: To test the hypothesis that the load of psychotropic agents was
      associated with subsequent dementia occurrence by a nationwide database. DESIGN:
      Propensity score matched case-control study. SETTING: National Health Insurance
      Research database. PARTICIPANTS: A total of 32,649 older people with dementia and
      32,649 matched dementia-free older people. MEASUREMENTS: Use of psychotropic
      drugs (anxiolytics, antipsychotics, hypnotics, and antidepressants), defined
      daily dose (DDD) of psychotropic drugs, diagnosis of dementia, and propensity
      score. INTERVENTION: None. RESULTS: Compared with nonusers, ever use of
      psychotropic agents was associated with higher odds of subsequent dementia
      [adjusted odds ratio (OR): 3.73; 95% confidence interval (CI) (3.59-3.88)].
      Significantly, the association was stronger with longer term exposure to
      psychotropic agents. The ORs at exposures of <90 days, 90-180 days, and >180
      days, were 3.14 (95% CI 3.01-3.28); 5.48 (5.07-5.93); and 7.54 (6.73-8.44),
      respectively. A similar and stronger association was identified when cumulative
      dose was used to measure the exposure of psychotropic agents [<90 DDDs, 3.40 (95%
      CI 3.26-3.54); 90-180 DDDs 6.38 (5.76-7.07), and >180 DDDs, 7.35 (6.29-8.58)].
      CONCLUSIONS: We found that a higher burden of psychotropic agents was strongly
      associated with a higher odds of subsequent dementia. Careful monitoring of any
      elderly who is prescribed or uptitrated psychotropic agents is highly
      recommended, especially those who combine use of more than one agent.
      Furthermore, providing timely assessment for cognitive function for older
      patients consuming psychotropic drugs is of great importance.

PMID- 24685408
TI  - Genetic variation in coding region of Aurora kinase A gene leads to cancer
      susceptibility.

PMID- 24685409
TI  - Control of data quality for population-based cancer survival analysis.
AB  - BACKGROUND: Population-based cancer survival is an important measure of the
      overall effectiveness of cancer care in a population. Population-based cancer
      registries collect data that enable the estimation of cancer survival. To ensure
      accurate, consistent and comparable survival estimates, strict control of data
      quality is required before the survival analyses are carried out. In this paper,
      we present a basis for data quality control for cancer survival. METHODS: We
      propose three distinct phases for the quality control. Firstly, each individual
      variable within a given record is examined to identify departures from the study
      protocol; secondly, each record is checked and excluded if it is ineligible or
      logically incoherent for analysis; lastly, the distributions of key
      characteristics in the whole dataset are examined for their plausibility.
      RESULTS: Data for patients diagnosed with bladder cancer in England between 1991
      and 2010 are used as an example to aid the interpretation of the differences in
      data quality. The effect of different aspects of data quality on survival
      estimates is discussed. CONCLUSIONS: We recommend that the results of data
      quality procedures should be reported together with the findings from survival
      analysis, to facilitate their interpretation.

PMID- 24685410
TI  - Increasing trend of contralateral prophylactic mastectomy: what are the factors
      behind this phenomenon?
AB  - INTRODUCTION: Numerous studies have shown a trend towards increasing rates of
      contralateral prophylactic mastectomy (CPM) in the US. In this review, we will
      explore the trend, possible causative factors and outcomes from CPM. METHODS: We
      performed a literature review of all relevant retrospective reviews, clinical
      trials and review articles regarding contralateral prophylactic mastectomy.
      RESULTS: Several studies have noted a four to fivefold increase in CPM in recent
      years; an increase most notable in younger patients. When surveyed, patients
      report that the most important factors affecting their choice of CPM include fear
      of cancer recurrence, genetic counseling/testing, family history or additional
      high risk factors, stress surrounding close follow up, the availability of
      reconstructive surgery and information provided about contralateral breast cancer
      (CBC) risk and risk for local recurrence. Women who have undergone CPM do report
      high satisfaction with the procedure and some studies suggest risk reduction.
      CONCLUSION: CPM rates have increased across the US and numerous factors have been
      reported to increase the likelihood of choosing CPM. Despite that bilateral
      mastectomy is associated with an increased risk of wound and overall
      postoperative complications for certain populations, this surgery appears to have
      psychological, cosmetic and possibly oncologic benefit.

PMID- 24685411
TI  - Epistaxis in a patient on antiplatelet therapy: not always benign.
AB  - Epistaxis in patients on antiplatelet and anticoagulant therapy is common and
      typically benign. We present a case of a rare nasal septal malignancy in a
      patient on antiplatelet therapy and discuss worrisome symptoms and signs which
      should prompt early referral to a specialist. 

PMID- 24685412
TI  - Orexin-A microinjection into the rostral ventromedial medulla causes
      antinociception on formalin test.
AB  - Orexins are produced from neurons which are restricted to a few regions of the
      lateral hypothalamus (LH), where they are important in pain modulation. The
      orexin receptors and orexinergic projections are localized in regions previously
      shown to play a role in pain modulation such as rostral ventromedial medulla
      (RVM). The effect of orexin-A (ORXA) microinjection into the RVM on nociceptive
      behaviors was examined using the formalin test. Microinjection of ORXA into the
      RVM, but not adjacent reticularis gigantocellularis (Gi) nucleus, decreased
      formalin induced nociceptive behaviors. Pretreatment with a selective OX1R
      antagonist, SB-334867 inhibited the antinociception produced by ORXA, while the
      administration of SB-334867 alone had no effect. These data demonstrate that ORXA
      induced antinociception in the formalin test is mediated in part through orexin1
      receptors in the RVM. 

PMID- 24685413
TI  - Homeopathy and antimicrobial resistance.

PMID- 24685414
TI  - Homeopathic treatment in addition to standard care in multi drug resistant
      pulmonary tuberculosis: a randomized, double blind, placebo controlled clinical
      trial.
AB  - BACKGROUND: Multi drug resistant-tuberculosis (MDR-TB) [resistant to Isoniazid
      and Rifampicin] is a major global public health problem. In India the incidence
      is rising in spite of implementation of Revised National Tuberculosis Control
      Program. Standard MDR-TB drugs are second generation antibiotics taken for 24-27
      months. The present study was undertaken to evaluate the efficacy of add on
      homeopathic intervention to the standard MDR-TB regimen (SR). METHODS: A
      randomized, double blind, placebo controlled study was conducted from 2003 to
      2008. 120 diagnosed MDR-TB patients (both culture positive and negative) were
      enrolled and randomized to receive Standard Regimen + individualized homeopathic
      medicine (SR + H) or Standard Regimen + identical placebo (SR + P). The medicines
      have been used in infrequent doses. The outcome measures were sputum conversion,
      changes in chest X-ray (CXR), hemoglobin, erythrocyte sedimentation rate (ESR),
      weight gain, and clinical improvement. RESULTS: There was an improvement in all
      the outcome measures as per intention to treat (ITT) and per protocol (PP)
      analyses. ITT analyses revealed sputum culture conversion from positive to
      negative in 23 (38.3%) in SR + H; 23 (38.3%) patients in SR + P group; (p =
      0.269) and 27 (55.1); 21 (42.8%), p = 0.225 as PP analyses. The mean weight gain
      in SR + H group was 2.4 +/- 4.9 and in SR + P was 0.8 +/- 4.4; [p = 0.071],
      reduction in ESR in SR + H was -8.7 +/- 13.2; SR + P was 3.9 +/- 15.4 [p =
      0.068]. The mean increase in hemoglobin was by 0.6 +/- 1.7 in SR + H & 0.3 +/-
      2.3 [p = 0.440] in SR + P group at 95% confidence interval. Statistically
      significant improvement was seen in CXR in 37 (61.7%) in SR + H and 20 (33.3%)
      patients in SR + P group (p = 0.002). Subgroup analyses of culture positive
      patients showed statistically significant improvement in CXR (p = 0.0005), weight
      gain (p = 0.026), increase in hemoglobin (p = 0.017) and reduction in ESR (p =
      0.025) with add on homeopathy. The cure rate was 11.4% more in SR + H group as
      compared to placebo group. Change in sputum culture conversion, was not
      statistically significant. CONCLUSION: Add on homeopathy in addition to standard
      therapy appears to improve outcome in MDR-TB. Larger scale studies using a
      standardized homeopathic treatment regime should be conducted.

PMID- 24685415
TI  - Do Homeopathic Pathogenetic Trials generate recognisable and reproducible symptom
      pictures?: Results from a pilot pathogenetic trial of Ozone 30c.
AB  - BACKGROUND: Homeopathic Pathogenetic Trials (HPTs) are a pillar of homeopathy, a
      key source of the symptoms characteristic of a particular homeopathic medicine.
      Homeopaths choose homeopathic medicines by comparing these remedy pictures with
      the symptoms the patient is presenting. Thus, recognition of these symptom sets
      underpins the clinical practice of homeopathy. OBJECTIVE: To test whether HPTs
      generate consistent and recognisable sets of symptoms in consecutive trials.
      DESIGN: Practising homeopaths, blinded to the homeopathic medicine under
      investigation, were given the set of symptoms generated during an unpublished HPT
      and asked to identify the homeopathic medicine used. HOMEOPATHIC TRIAL SUBSTANCE:
      Ozone, prepared by homeopathic method to the ultramolecular dilution of 30c (10(
      60) dilution), was chosen at random from twenty potential medicines. RESULTS:
      Seven practising homeopaths were asked to make three guesses as to the identity
      of the remedy. Initially from the full list of possible remedies (N = 2372). Two
      of the seven homeopaths guessed the identity of the remedy correctly (p <
      0.0001). Subsequently, when their choice of possible medicines was restricted to
      a list of 20, the same two homeopaths selected the correct medicine, however none
      of the other practising homeopaths did so (p = 0.2). DISCUSSION: The selection of
      the correct homeopathic medicine from the unrestricted list (N = 2372 medicines)
      by two homeopaths is noteworthy given that the homeopathic medicine used during
      the HPT was diluted well beyond Avogadro's number and would not be expected to
      produce any detectable or recognisable symptomatology. Possible reasons why the
      remaining five homeopaths did not guess correctly are discussed. CONCLUSION: The
      results show that practising homeopaths may be able to correctly identify a
      homeopathic medicine from the set of symptoms generated during an HPT. This
      suggests that such symptom pictures generated by taking an ultramolecular
      homeopathic medicine are recognisable and specific to the substance taken. Since
      identification of the remedy was based on past HPT information held in the
      materia medica, this demonstrates that HPT-generated symptom pictures are
      reproducible, thus validating the HPT methodology. These promising preliminary
      findings warrant replication; possible improvements to the trial design to be
      incorporated in future studies were identified.

PMID- 24685416
TI  - Reproducibility of effects of homeopathically potentised gibberellic acid on the
      growth of Lemna gibba L. in a randomised and blinded bioassay.
AB  - BACKGROUND: Reproducibility of basic research investigations in homeopathy is
      challenging. This study investigated if formerly observed effects of
      homeopathically potentised gibberellic acid (GA3) on growth of duckweed (Lemna
      gibba L.) were reproducible. METHODS: Duckweed was grown in potencies (14x-30x)
      of GA3 and one time succussed and unsuccussed water controls. Outcome parameter
      area-related growth rate was determined by a computerised image analysis system.
      Three series including five independent blinded and randomised potency
      experiments (PE) each were carried out. System stability was controlled by three
      series of five systematic negative control (SNC) experiments. Gibbosity (a
      specific growth state of L. gibba) was investigated as possibly essential factor
      for reactivity of L. gibba towards potentised GA3 in one series of potency and
      SNC experiments, respectively. RESULTS: Only in the third series with gibbous L.
      gibba L. we observed a significant effect (p = 0.009, F-test) of the homeopathic
      treatment. However, growth rate increased in contrast to the former study, and
      most biologically active potency levels differed. Variability in PE was lower
      than in SNC experiments. The stability of the experimental system was verified by
      the SNC experiments. CONCLUSIONS: Gibbosity seems to be a necessary condition for
      reactivity of L. gibba to potentised GA3. Further still unknown conditions seem
      to govern effect direction and the pattern of active and inactive potency levels.
      When designing new reproducibility studies, the physiological state of the test
      organism must be considered. Variability might be an interesting parameter to
      investigate effects of homeopathic remedies in basic research.

PMID- 24685417
TI  - Exploring the effects of homeopathic Apis mellifica preparations on human gene
      expression profiles.
AB  - BACKGROUND: Diluted preparations obtained from Apis mellifica are reported in the
      homeopathic literature to have anti-inflammatory activity. The present study was
      designed to explore the effects on global gene expression profiles of human cells
      by means of microarrays, using Apis mellifica mother tincture (TM) and its 3C,
      5C, 7C dynamized dilutions; the technique employed allowed us to study the
      changes in gene expression at concentrations much lower than those associated
      with pharmacological responses. METHODS: An RWPE-1 cell line (human immortalized
      prostate epithelial cells) was used to study the effects on global gene
      expression by transcriptomic analysis. RESULTS: Apis mellifica TM and its 3C, 5C,
      7C dynamized dilutions modulated hundreds of genes; using cluster analysis we
      observed groups of genes up- or down-regulated with similar expression profiles
      among treatments; other genes showed opposite regulation profiles at low and high
      dilutions of Apis mellifica, suggesting a hormetic response. In particular, genes
      involved in cytokine expression, inflammatory processes, anti-oxidative responses
      and proteasome degradation were differentially, and sometimes divergently
      expressed by the TM or by Apis mellifica 3C, 5C and 7C dilutions. We confirmed
      these data by RT-PCR analyses on 5 selected candidate genes (IL1beta, CD46, ATF1,
      UBE2Q2 and MT1X). CONCLUSIONS: Apis mellifica TM modifies gene expression in
      human cells and has inhibitory effects on regulatory processes of inflammation;
      in addition, extremely diluted dynamized dilutions (3C, 5C and 7C) still exert
      significant effects on genes involved in inflammation and oxidative stress.

PMID- 24685418
TI  - Anti-rheumatoid and anti-oxidant activity of homeopathic Guaiacum officinale in
      an animal model.
AB  - BACKGROUND: Homeopathy is a popular form of complementary and alternative
      medicine. Guaiacum extract is said to be useful for pain and inflammation, but
      there appears to be no scientific evidence to support this. AIMS: The aim of the
      present study was to evaluate the anti-rheumatic and anti-oxidant activity of
      homeopathic preparations of Guaiacum officinale (Gua) on experimental animal
      model. DESIGN: Rheumatoid arthritis (RA) was induced in male albino rats by
      Freund's complete adjuvant (FCA) at a dose of (0.25 mg heat killed Mycobacterium
      tuberculosis/ml of emulsion). Gua mother tincture (MT) (prepared from the latex
      part of the plant) (MT), Gua 30cc and 200cc were purchased commercially from King
      Company, Kolkata, India. Male albino Wistar rats (130 +/- 10 g) were divided into
      6 groups: Sham control; Arthritis control; Standard treatment indomethacin (0.25
      mg 100 g(-1) p.o. * 5 alternative days), Gua MT (1 ml kg(-1) p.o. * 5 days)
      treated; Gua (30c 1 ml kg(-1) p.o. * 5 days) treated; Gua (200c; 1 ml kg(-1) p.o.
      * 5 days) treated. Anti-rheumatic activity was examined through physical,
      urinary, serum parameters. All the results were expressed in terms of mean +/-
      SEM (statistical error of mean n = 6) at each dose level. The level of
      significance was determined through one-way analysis of variance (ANOVA), p <
      0.05 was considered significant. RESULTS: It was observed that body weight, ankle
      and knee diameter, urinary parameters (hydroxyproline (OH-P), glucosamine,
      calcium (Ca(2)(+)), creatinine (CRE), phosphate (PO4(3)(-))), serum ACP (acid
      phosphatase)/ALP (alkaline phosphatase)/Ca(2+)/CRE/PO4(3-)/gamma-glutamyl
      transferase (GGT)/Lipid peroxidation (LPO)/Glutathione (GSH)/Superoxide dismutase
      (SOD)/Catalase, serum GGT, serum interleukins like IL-1beta/CINC-1/PGE2/TNF
      alpha/IL-6, IL-12/IL-4/IL-6 levels were significantly affected. After treatment
      with Guaiacum in all 3 regimes was associated with normalization of these
      parameters compared to control group. CONCLUSION: These findings suggest that
      homeopathic G. officinale possesses anti-rheumatic and anti-oxidant activity in
      experimental animal and these activities may be more significant in higher
      potencies.

PMID- 24685419
TI  - Effects of a homeopathic complex on the performance and cortisol levels in Nile
      tilapia (Oreochromis niloticus).
AB  - BACKGROUND: Intensive fish farming results in stress adversely effecting the
      performance of farmed fish. Plasma cortisol is a validated measure of stress in
      fish. We evaluated the effect of a homeopathic complex on the cortisol level of
      Nile tilapias (Oreochromis niloticus). METHOD: 60 animals with approximate
      average weight of 100 g each at the start of experiment were randomly distributed
      in six glass fiber water tanks, capacity 1000 liters, with a daily water renewal
      rate of 20%. They received one of two treatments: 30 animals in control treatment
      and 30 animals receiving the homeopathic complex Homeopatila 100. On days 1, 30
      and 60, all fish were anesthetized and blood was collected by puncture on the
      caudal vein, to determine the levels of circulating cortisol. RESULTS: At the end
      of the experiment the fish receiving a homeopathic complex, had significantly
      lower circulating cortisol level (17.96 ng/mL +/- 0.95) than the control group
      (38.68 ng/mL +/- 1.21) (p < 0.05). CONCLUSIONS: Cortisol levels were
      significantly lower in the treated group than control, and the fish were larger
      in the treated group.

PMID- 24685420
TI  - The mathematics of dilution.
AB  - The major objection to homeopathic medicine is that the doses of medicine
      prescribed in some cases are too dilute for any active ingredient to be present.
      The medicines would hence be rendered inactive, necessitating novel explanations
      for the action. A further examination of dilution in the light of the Langmuir
      equation shows that homeopathic medicines may not be as dilute as a simplistic
      application of Avogadro's Principle suggests, due to surface effects. 

PMID- 24685421
TI  - Depression treated by homeopaths: a study protocol for a pragmatic cohort
      multiple randomised controlled trial.
AB  - BACKGROUND: The most commonly recommended treatments for depression are
      psychological/psychotherapeutic treatments, and antidepressant drugs. However, 38
      percent of patients with depression do not use these recommended treatments. Some
      patients seek homeopathic treatment for depression, but insufficient evidence
      exists to conclude as to the effectiveness, cost-effectiveness and safety of
      treatment by homeopaths for patients with depression. The aim of this trial is to
      evaluate the acceptability and comparative clinical and cost-effectiveness of the
      offer of adjunctive treatment provided by homeopaths for patients with self
      reported depression. METHOD: This pragmatic randomised controlled trial is
      embedded within the population based South Yorkshire Cohort (SYC) of whom nine
      percent self-report long-term depression. The SYC is designed to facilitate
      'cohort multiple' randomised controlled trials (cmRCT). A self-completed
      questionnaire will be used to both screen and collect baseline data from
      potential trial participants. The primary outcome is PHQ-9. One-hundred-and-sixty
      two participants will be randomly selected to the intervention group (Offer of
      treatment by a homeopath). The results of the Offer and the No Offer groups will
      be compared at 6 and 12 months using both an intention to treat (ITT) and
      complier average causal effect (CACE) analysis. Cost-effectiveness analysis will
      involve calculation of quality adjusted life year (QALY). In order to help
      interpret the quantitative findings a selection of up to 30 patients in the offer
      group will be invited to participate in qualitative interviews after the first
      consultation and after a minimum of 6 months. Interviews will be assessed by two
      researchers and results will be analysed using thematic analysis. Triangulation
      will be used to combine results from qualitative and quantitative methodologies
      at the interpretation stage, to see if results agree, offer complementary
      information on the same issue or contradict each other.

PMID- 24685422
TI  - New approaches within the history and theory of medicine and their relevance for
      homeopathy.
AB  - Conventional sciences have brought forth a wealth of knowledge and benefits, but
      they have not always been clear and precise about their legitimate scope and
      methodological limitations. In contrast, new and critical approaches in modern
      sciences question and reflect their own presuppositions, dependencies, and
      constraints. Examples are quantum physics, theory and history of science, as well
      as theory and history of medicine, sociology, and economics. In this way,
      deprecative dogmatism and animosity amongst sciences ought to be lessened, while
      the field opens up for each science to redefine its appropriate place in society.
      This would appear to be a chance for homeopathy, as new approaches, especially
      within the social and economic sciences, suggest that being a follower of Samuel
      Hahnemann (1755-1843) may have advantages and privileges that conventional
      medicine seems to be lacking and whose relevance was overlooked during the rise
      of economic thinking in the last two centuries. 

PMID- 24685423
TI  - Homeopathy, phenomenology and the unprejudiced observer: response to Swayne and
      Whitmarsh: Homeopathy (2013) 102, pp. 157-159; 225-229.

PMID- 24685424
TI  - Homeopathy and phenomenology: response to David Levy.

PMID- 24685425
TI  - Homeopathy and phenomenology: response to David Levy.

PMID- 24685426
TI  - Statin therapy and related risk of new-onset type 2 diabetes mellitus.
AB  - The use of statins for cardiovascular disease (CVD) prevention is clearly
      supported by clinical evidence. Although statin therapy is rather well tolerated,
      recent data from prospective and retrospective clinical trials and related meta
      analyses suggest an increased incidence of new-onset type 2 diabetes mellitus
      (T2DM) in association with such treatment. The incidence of this adverse effect
      is not negligible, especially for specific subsets of patients, such as women,
      elderly, presence of familial history of T2DM and Asian ethnicity. Statin-driven
      T2DM appears to be a medication class-effect, mostly not related to potency nor
      to individual statin, as well as to be independent of previous history of CVD.
      Therefore, implementation of strategies for identification of patients using
      statins and at specific risk of incident T2DM, as well as of different
      therapeutic options is important and is discussed in this article. As most
      authors emphasized that benefits of CVD reduction by statin therapy seem to far
      exceed the risk of T2DM development itself, these medications remain the
      cornerstone for primary and secondary CVD prevention, although a specific
      attention to glucose metabolism and metabolic syndrome features should be payed
      before and during statin treatment, especially in cohorts at greater risk. 

PMID- 24685427
TI  - Relaxed tRNA specificity of the Staphylococcus aureus aspartyl-tRNA synthetase
      enables RNA-dependent asparagine biosynthesis.
AB  - The human pathogen Staphylococcus aureus is an asparagine prototroph despite its
      genome not encoding an asparagine synthetase. S. aureus does use an asparaginyl
      tRNA synthetase (AsnRS) to directly ligate asparagine to tRNA(Asn). The S. aureus
      genome also codes for one aspartyl-tRNA synthetase (AspRS). Here we demonstrate
      the lone S. aureus aspartyl-tRNA synthetase has relaxed tRNA specificity and can
      be used with the amidotransferase GatCAB to synthesize asparagine on tRNA(Asn).
      S. aureus thus encodes both the direct and indirect routes for Asn-tRNA(Asn)
      formation while encoding only one aspartyl-tRNA synthetase. The presence of the
      indirect pathway explains how S. aureus synthesizes asparagine without either
      asparagine synthetase. 

PMID- 24685428
TI  - The dynamic complex of cytochrome c6 and cytochrome f studied with paramagnetic
      NMR spectroscopy.
AB  - The rapid transfer of electrons in the photosynthetic redox chain is achieved by
      the formation of short-lived complexes of cytochrome b6f with the electron
      transfer proteins plastocyanin and cytochrome c6. A balance must exist between
      fast intermolecular electron transfer and rapid dissociation, which requires the
      formation of a complex that has limited specificity. The interaction of the
      soluble fragment of cytochrome f and cytochrome c6 from the cyanobacterium Nostoc
      sp. PCC 7119 was studied using NMR spectroscopy and X-ray diffraction. The
      crystal structures of wild type, M58H and M58C cytochrome c6 were determined. The
      M58C variant is an excellent low potential mimic of the wild type protein and was
      used in chemical shift perturbation and paramagnetic relaxation NMR experiments
      to characterize the complex with cytochrome f. The interaction is highly dynamic
      and can be described as a pure encounter complex, with no dominant stereospecific
      complex. Ensemble docking calculations and Monte-Carlo simulations suggest a
      model in which charge-charge interactions pre-orient cytochrome c6 with its haem
      edge toward cytochrome f to form an ensemble of orientations with extensive
      contacts between the hydrophobic patches on both cytochromes, bringing the two
      haem groups sufficiently close to allow for rapid electron transfer. This model
      of complex formation allows for a gradual increase and decrease of the
      hydrophobic interactions during association and dissociation, thus avoiding a
      high transition state barrier that would slow down the dissociation process. 

PMID- 24685429
TI  - The architecture of Rhodobacter sphaeroides chromatophores.
AB  - The chromatophores of Rhodobacter (Rb.) sphaeroides represent a minimal bio
      energetic system, which efficiently converts light energy into usable chemical
      energy. Despite extensive studies, several issues pertaining to the morphology
      and molecular architecture of this elemental energy conversion system remain
      controversial or unknown. To tackle these issues, we combined electron microscope
      tomography, immuno-electron microscopy and atomic force microscopy. We found that
      the intracellular Rb. sphaeroides chromatophores form a continuous reticulum
      rather than existing as discrete vesicles. We also found that the cytochrome bc1
      complex localizes to fragile chromatophore regions, which most likely constitute
      the tubular structures that interconnect the vesicles in the reticulum. In
      contrast, the peripheral light-harvesting complex 2 (LH2) is preferentially
      hexagonally packed within the convex vesicular regions of the membrane network.
      Based on these observations, we propose that the bc1 complexes are in the inter
      vesicular regions and surrounded by reaction center (RC) core complexes, which in
      turn are bounded by arrays of peripheral antenna complexes. This arrangement
      affords rapid cycling of electrons between the core and bc1 complexes while
      maintaining efficient excitation energy transfer from LH2 domains to the RCs. 

PMID- 24685430
TI  - The H(+)-ATP synthase: a gate to ROS-mediated cell death or cell survival.
AB  - Cellular oxidative stress results from the increased generation of reactive
      oxygen species and/or the dysfunction of the antioxidant systems. Most
      intracellular reactive oxygen species derive from superoxide radical although the
      majority of the biological effects of reactive oxygen species are mediated by
      hydrogen peroxide. In this contribution we overview the major cellular sites of
      reactive oxygen species production, with special emphasis in the mitochondrial
      pathways. Reactive oxygen species regulate signaling pathways involved in
      promoting survival and cell death, proliferation, metabolic regulation, the
      activation of the antioxidant response, the control of iron metabolism and Ca(2+)
      signaling. The reversible oxidation of cysteines in transducers of reactive
      oxygen species is the primary mechanism of regulation of the activity of these
      proteins. Next, we present the mitochondrial H(+)-ATP synthase as a core hub in
      energy and cell death regulation, defining both the rate of energy metabolism and
      the reactive oxygen species-mediated cell death in response to chemotherapy. Two
      main mechanisms that affect the expression and activity of the H(+)-ATP synthase
      down-regulate oxidative phosphorylation in prevalent human carcinomas. In this
      context, we emphasize the prominent role played by the ATPase Inhibitory Factor 1
      in human carcinogenesis as an inhibitor of the H(+)-ATP synthase activity and a
      mediator of cell survival. The ATPase Inhibitory Factor 1 promotes metabolic
      rewiring to an enhanced aerobic glycolysis and the subsequent production of
      mitochondrial reactive oxygen species. The generated reactive oxygen species are
      able to reprogram the nucleus to support tumor development by arresting cell
      death. Overall, we discuss the cross-talk between reactive oxygen species
      signaling and mitochondrial function that is crucial in determining the cellular
      fate. This article is part of a Special Issue entitled: 18th European
      Bioenergetic Conference. 

PMID- 24685431
TI  - Water exchange in manganese-based water-oxidizing catalysts in photosynthetic
      systems: from the water-oxidizing complex in photosystem II to nano-sized
      manganese oxides.
AB  - The water-oxidizing complex (WOC), also known as the oxygen-evolving complex
      (OEC), of photosystem II in oxygenic photosynthetic organisms efficiently
      catalyzes water oxidation. It is, therefore, responsible for the presence of
      oxygen in the Earth's atmosphere. The WOC is a manganese-calcium (Mn4CaO5(H2O)4)
      cluster housed in a protein complex. In this review, we focus on water exchange
      chemistry of metal hydrates and discuss the mechanisms and factors affecting this
      chemical process. Further, water exchange rates for both the biological cofactor
      and synthetic manganese water splitting are discussed. The importance of fully
      unveiling the water exchange mechanism to understand the chemistry of water
      oxidation is also emphasized here. This article is part of a special issue
      entitled: photosynthesis research for sustainability: keys to produce clean
      energy.

PMID- 24685432
TI  - Reaction of wild-type and Glu243Asp variant yeast cytochrome c oxidase with O2.
AB  - We have studied internal electron transfer during the reaction of Saccharomyces
      cerevisiae mitochondrial cytochrome c oxidase with dioxygen. Similar absorbance
      changes were observed with this yeast oxidase as with the previously studied
      Rhodobacter sphaeroides and bovine mitochondrial oxidases, which suggests that
      the reaction proceeds along the same trajectory. However, notable differences
      were observed in rates and electron-transfer equilibrium constants of specific
      reaction steps, for example the ferryl (F) to oxidized (O) reaction was faster
      with the yeast (0.4ms) than with the bovine oxidase (~1ms) and a larger fraction
      CuA was oxidized with the yeast than with the bovine oxidase in the peroxy (PR)
      to F reaction. Furthermore, upon replacement of Glu243, located at the end of the
      so-called D proton pathway, by Asp the PR->F and F->O reactions were slowed by
      factors of ~3 and ~10, respectively, and electron transfer from CuA to heme a
      during the PR->F reaction was not observed. These data indicate that during
      reduction of dioxygen protons are transferred through the D pathway, via Glu243,
      to the catalytic site in the yeast mitochondrial oxidase. This article is part of
      a Special Issue entitled: 18th European Bioenergetic Conference. 

PMID- 24685433
TI  - External validation of a prognostic model predicting overall survival in
      metastatic castrate-resistant prostate cancer patients treated with abiraterone.
AB  - A prognostic model was derived from the population of the COU-AA-301 phase 3
      trial for metastatic castrate-resistant prostate cancer patients treated with
      abiraterone after docetaxel, and it stratifies patients into three risk groups
      based on clinical parameters. We validated this model in an independent cohort of
      patients treated with abiraterone after docetaxel outside a clinical trial (group
      A; n=94) and explored its utility in patients treated with abiraterone in the
      prechemotherapy setting (group B; n=64). For group A, median overall survival
      (mOS) was significantly different across the three prognostic groups (good: n=39,
      mOS: 21.8 mo; intermediate: n=44, mOS: 10.6 mo; poor: n=7, mOS: 6.8 mo; p<0.001;
      area under the curve [AUC]: 0.71). Analysis of group B confirmed the ability of
      the model to prognosticate for survival in the prechemotherapy setting: (good:
      n=44, mOS: 45.6 mo; intermediate or poor: n=20, mOS: 34.5 mo; p=0.042; AUC:
      0.61). These results serve to validate the prognostic model in an independent
      population treated with abiraterone after docetaxel and support clinical
      implementation of the score. Calibration of the model was poorer in patients
      receiving abiraterone prechemotherapy. Prospective evaluation of this model in
      clinical trials is needed.

PMID- 24685434
TI  - Metabolic syndrome as a marker for prostate cancer: still a work in progress.

PMID- 24685435
TI  - Is it possible that one patient may again experience a response to abiraterone
      acetate withdrawal during an abiraterone acetate rechallenge?

PMID- 24685436
TI  - Mapping glucose-mediated gut-to-brain signalling pathways in humans.
AB  - OBJECTIVES: Previous fMRI studies have demonstrated that glucose decreases the
      hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS
      response to glucose have not been defined. We recently demonstrated that the
      slowing of gastric emptying by glucose is dependent on activation of the gut
      peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic
      resonance imaging this study aimed to determine the whole brain response to
      glucose, and whether CCK plays a central role. EXPERIMENTAL DESIGN: Changes in
      blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12
      healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing
      with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9%
      saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder
      volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined.
      Hunger, fullness and nausea scores were also recorded. PRINCIPAL OBSERVATIONS:
      Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced
      gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD
      signal, relative to saline, in the brainstem and hypothalamus as well as the
      cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD
      signal decrease was negatively correlated with the rise in blood glucose and
      insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent
      increase in BOLD signal only in the motor cortex. CONCLUSIONS: Glucose induces
      site-specific differences in BOLD response in the human brain; the brainstem and
      hypothalamus show a CCK1 receptor-independent reduction which is likely to be
      mediated by a circulatory effect of glucose and insulin, whereas the motor cortex
      shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1
      receptor-dependent neural pathway.

PMID- 24685437
TI  - Non-invasive MRI measurements of venous oxygenation, oxygen extraction fraction
      and oxygen consumption in neonates.
AB  - BACKGROUND AND PURPOSE: Brain oxygen consumption reflects neuronal activity and
      can therefore be used to investigate brain development or neuronal injury in
      neonates. In this paper we present the first results of a non-invasive MRI method
      to evaluate whole brain oxygen consumption in neonates. MATERIALS AND METHODS:
      For this study 51 neonates were included. The T1 and T2 of blood in the sagittal
      sinus were fitted using the 'T2 prepared tissue relaxation inversion recovery'
      pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation
      and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic
      rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial
      spin labeling whole brain cerebral blood flow (CBF) measurements. RESULTS: Venous
      oxygenation was 59+/-14% (mean+/-sd), OEF was 40+/-14%, CBF was 14+/-5ml/100g/min
      and CMRO2 was 30+/-12MUmol/100g/min. The OEF in preterms at term-equivalent age
      was higher than in the preterms and in the infants with hypoxic-ischemic
      encephalopathy (p<0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and
      <0.01, respectively) with postnatal age. CONCLUSION: We presented an MRI
      technique to evaluate whole-brain oxygen consumption in neonates non-invasively.
      The measured values are in line with reference values found by invasive
      measurement techniques. Preterms and infants with HIE demonstrated significant
      lower oxygen extraction fraction than the preterms at term-equivalent age. This
      could be due to decreased neuronal activity as a reflection of brain development
      or as a result of tissue damage, increased cerebral blood flow due to immature or
      impaired autoregulation, or could be caused by differences in postnatal age.

PMID- 24685438
TI  - Proteome changes in platelets after pathogen inactivation--an interlaboratory
      consensus.
AB  - Pathogen inactivation (PI) of platelet concentrates (PCs) reduces the
      proliferation/replication of a large range of bacteria, viruses, and parasites as
      well as residual leucocytes. Pathogen-inactivated PCs were evaluated in various
      clinical trials showing their efficacy and safety. Today, there is some debate
      over the hemostatic activity of treated PCs as the overall survival of PI
      platelets seems to be somewhat reduced, and in vitro measurements have identified
      some alterations in platelet function. Although the specific lesions resulting
      from PI of PCs are still not fully understood, proteomic studies have revealed
      potential damages at the protein level. This review merges the key findings of
      the proteomic analyses of PCs treated by the Mirasol Pathogen Reduction
      Technology, the Intercept Blood System, and the Theraflex UV-C system,
      respectively, and discusses the potential impact on the biological functions of
      platelets. The complementarities of the applied proteomic approaches allow the
      coverage of a wide range of proteins and provide a comprehensive overview of PI
      mediated protein damage. It emerges that there is a relatively weak impact of PI
      on the overall proteome of platelets. However, some data show that the different
      PI treatments lead to an acceleration of platelet storage lesions, which is in
      agreement with the current model of platelet storage lesion in pathogen
      inactivated PCs. Overall, the impact of the PI treatment on the proteome appears
      to be different among the PI systems. Mirasol impacts adhesion and platelet shape
      change, whereas Intercept seems to impact proteins of intracellular platelet
      activation pathways. Theraflex influences platelet shape change and aggregation,
      but the data reported to date are limited. This information provides the basis to
      understand the impact of different PI on the molecular mechanisms of platelet
      function. Moreover, these data may serve as basis for future developments of PI
      technologies for PCs. Further studies should address the impact of both the PI
      and the storage duration on platelets in PCs because PI may enable the extension
      of the shelf life of PCs by reducing the bacterial contamination risk. 

PMID- 24685439
TI  - Dual orexin receptor antagonist 12 inhibits expression of proteins in neurons and
      glia implicated in peripheral and central sensitization.
AB  - Sensitization and activation of trigeminal nociceptors is implicated in prevalent
      and debilitating orofacial pain conditions including temporomandibular joint
      (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate
      many physiological processes and are reported to modulate nociception. To
      determine the role of orexins in an inflammatory model of trigeminal activation,
      the effects of a dual orexin receptor antagonist (DORA-12) on levels of proteins
      that promote peripheral and central sensitization and changes in nocifensive
      responses were investigated. In adult male Sprague-Dawley rats, mRNA for orexin
      receptor 1 (OX1R) and receptor 2 (OX2R) were detected in trigeminal ganglia and
      spinal trigeminal nucleus (STN). OX1R immunoreactivity was localized primarily in
      neuronal cell bodies in the V3 region of the ganglion and in laminas I-II of the
      STN. Animals injected bilaterally with complete Freund's adjuvant (CFA) in the
      TMJ capsule exhibited increased expression of P-p38, P-ERK, and lba1 in
      trigeminal ganglia and P-ERK and lba1 in the STN at 2 days post injection.
      However, levels of each of these proteins in rats receiving daily oral DORA-12
      were inhibited to near basal levels. Similarly, administration of DORA-12 on days
      3 and 4 post CFA injection in the TMJ effectively inhibited the prolonged
      stimulated expression of protein kinase A, NFkB, and Iba1 in the STN on day 5
      post injection. While injection of CFA mediated a nocifensive response to
      mechanical stimulation of the orofacial region at 2h and 3 and 5 days post
      injection, treatment with DORA-12 suppressed the nocifensive response on day 5.
      Somewhat surprisingly, nocifensive responses were again observed on day 10 post
      CFA stimulation in the absence of daily DORA-12 administration. Our results
      provide evidence that DORA-12 can inhibit CFA-induced stimulation of trigeminal
      sensory neurons by inhibiting expression of proteins associated with
      sensitization of peripheral and central neurons and nociception.

PMID- 24685440
TI  - Multiple electrode aggregometry in severe obstetric haemorrhage.

PMID- 24685441
TI  - Coinfection of tick cell lines has variable effects on replication of
      intracellular bacterial and viral pathogens.
AB  - Ticks transmit various human and animal microbial pathogens and may harbour more
      than one pathogen simultaneously. Both viruses and bacteria can trigger, and may
      subsequently suppress, vertebrate host and arthropod vector anti-microbial
      responses. Microbial coinfection of ticks could lead to an advantage or
      disadvantage for one or more of the microorganisms. In this preliminary study,
      cell lines derived from the ticks Ixodes scapularis and Ixodes ricinus were
      infected sequentially with 2 arthropod-borne pathogens, Borrelia burgdorferi
      s.s., Ehrlichia ruminantium, or Semliki Forest virus (SFV), and the effect of
      coinfection on the replication of these pathogens was measured. Prior infection
      of tick cell cultures with the spirochaete B. burgdorferi enhanced subsequent
      replication of the rickettsial pathogen E. ruminantium whereas addition of
      spirochaetes to cells infected with E. ruminantium had no effect on growth of the
      latter. Both prior and subsequent presence of B. burgdorferi also had a positive
      effect on SFV replication. Presence of E. ruminantium or SFV had no measurable
      effect on B. burgdorferi growth. In tick cells infected first with E. ruminantium
      and then with SFV, virus replication was significantly higher across all time
      points measured (24, 48, 72h post infection), while presence of the virus had no
      detectable effect on bacterial growth. When cells were infected first with SFV
      and then with E. ruminantium, there was no effect on replication of either
      pathogen. The results of this preliminary study indicate that interplay does
      occur between different pathogens during infection of tick cells. Further study
      is needed to determine if this results from direct pathogen-pathogen interaction
      or from effects on host cell defences, and to determine if these observations
      also apply in vivo in ticks. If presence of one pathogen in the tick vector
      results in increased replication of another, this could have implications for
      disease transmission and incidence.

PMID- 24685442
TI  - Cherenkov video imaging allows for the first visualization of radiation therapy
      in real time.
AB  - PURPOSE: To determine whether Cherenkov light imaging can visualize radiation
      therapy in real time during breast radiation therapy. METHODS AND MATERIALS: An
      intensified charge-coupled device (CCD) camera was synchronized to the 3.25-MUs
      radiation pulses of the clinical linear accelerator with the intensifier set *
      100. Cherenkov images were acquired continuously (2.8 frames/s) during
      fractionated whole breast irradiation with each frame an accumulation of 100
      radiation pulses (approximately 5 monitor units). RESULTS: The first patient
      images ever created are used to illustrate that Cherenkov emission can be
      visualized as a video during conditions typical for breast radiation therapy,
      even with complex treatment plans, mixed energies, and modulated treatment
      fields. Images were generated correlating to the superficial dose received by the
      patient and potentially the location of the resulting skin reactions. Major blood
      vessels are visible in the image, providing the potential to use these as
      biological landmarks for improved geometric accuracy. The potential for this
      system to detect radiation therapy misadministrations, which can result from
      hardware malfunction or patient positioning setup errors during individual
      fractions, is shown. CONCLUSIONS: Cherenkoscopy is a unique method for
      visualizing surface dose resulting in real-time quality control. We propose that
      this system could detect radiation therapy errors in everyday clinical practice
      at a time when these errors can be corrected to result in improved safety and
      quality of radiation therapy.

PMID- 24685443
TI  - Prevalence and predictors of neoadjuvant therapy for stage IIIA non-small cell
      lung cancer in the National Cancer Database: importance of socioeconomic status
      and treating institution.
AB  - PURPOSE: The optimal locoregional therapy for stage IIIA non-small cell lung
      cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and
      neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies.
      In this study, we used the National Cancer Database to determine the prevalence
      and predictors of NT in a large, modern cohort of patients. METHODS AND
      MATERIALS: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003
      and 2010 at programs accredited by the Commission on Cancer were included.
      Predictors were categorized as clinical, time/geographic, socioeconomic, and
      institutional. In accord with the National Cancer Database, institutions were
      classified as academic/research program and as comprehensive and noncomprehensive
      community cancer centers. Logistic regression and random effects multilevel
      logistic regression were performed for univariable and multivariable analyses,
      respectively. RESULTS: The cohort consisted of 18,581 patients, 3,087 (16.6%) of
      whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The
      prevalence of NT-S was constant over time, but there were significant relative
      31% and 30% decreases in pneumonectomy and right-sided pneumonectomy,
      respectively, over time (P trend <.02). In addition to younger age, lower T
      stage, and favorable comorbidity score, indicators of higher socioeconomic status
      were strong independent predictors of NT-S, including white race, higher income,
      and private/managed insurance. The type of institution (academic/research program
      vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54
      and 2.08, respectively) strongly predicted NT-S, but treatment volume did not.
      CONCLUSIONS: Neoadjuvant therapy followed by surgery was an uncommon treatment
      approach in Commission on Cancer programs, and the prevalence of postinduction
      pneumonectomy decreased over time. Higher socioeconomic status and treatment at
      academic institutions were significant predictors of NT-S. Further research
      should be performed to enable a better understanding of these disparities.

PMID- 24685444
TI  - Workflow enhancement (WE) improves safety in radiation oncology: putting the WE
      and team together.
AB  - PURPOSE: To review the impact of a workflow enhancement (WE) team in reducing
      treatment errors that reach patients within radiation oncology. METHODS AND
      MATERIALS: It was determined that flaws in our workflow and processes resulted in
      errors reaching the patient. The process improvement team (PIT) was developed in
      2010 to reduce errors and was later modified in 2012 into the current WE team.
      Workflow issues and solutions were discussed in PIT and WE team meetings. Due to
      tensions within PIT that resulted in employee dissatisfaction, there was a 6
      month hiatus between the end of PIT and initiation of the renamed/redesigned WE
      team. In addition to the PIT/WE team forms, the department had separate incident
      forms to document treatment errors reaching the patient. These incident forms are
      rapidly reviewed and monitored by our departmental and institutional quality and
      safety groups, reflecting how seriously these forms are treated. The number of
      these incident forms was compared before and after instituting the WE team.
      RESULTS: When PIT was disbanded, a number of errors seemed to occur in
      succession, requiring reinstitution and redesign of this team, rebranded the WE
      team. Interestingly, the number of incident forms per patient visits did not
      change when comparing 6 months during the PIT, 6 months during the hiatus, and
      the first 6 months after instituting the WE team (P=.85). However, 6 to 12 months
      after instituting the WE team, the number of incident forms per patient visits
      decreased (P=.028). After the WE team, employee satisfaction and commitment to
      quality increased as demonstrated by Gallup surveys, suggesting a correlation to
      the WE team. CONCLUSIONS: A team focused on addressing workflow and improving
      processes can reduce the number of errors reaching the patient. Time is necessary
      before a reduction in errors reaching patients will be seen.

PMID- 24685445
TI  - Evaluation of on-board kV cone beam computed tomography-based dose calculation
      with deformable image registration using Hounsfield unit modifications.
AB  - PURPOSE: The purpose of this study was to estimate the accuracy of the dose
      calculation of On-Board Imager (Varian, Palo Alto, CA) cone beam computed
      tomography (CBCT) with deformable image registration (DIR), using the multilevel
      threshold (MLT) algorithm and histogram matching (HM) algorithm in pelvic
      radiation therapy. METHODS AND MATERIALS: One pelvis phantom and 10 patients with
      prostate cancer treated with intensity modulated radiation therapy were studied.
      To minimize the effect of organ deformation and different Hounsfield unit values
      between planning CT (PCT) and CBCT, we modified CBCT (mCBCT) with DIR by using
      the MLT (mCBCT(MLT)) and HM (mCBCT(HM)) algorithms. To evaluate the accuracy of
      the dose calculation, we compared dose differences in dosimetric parameters (mean
      dose [D(mean)], minimum dose [D(min)], and maximum dose [D(max)]) for planning
      target volume, rectum, and bladder between PCT (reference) and CBCTs or mCBCTs.
      Furthermore, we investigated the effect of organ deformation compared with DIR
      and rigid registration (RR). We determined whether dose differences between PCT
      and mCBCTs were significantly lower than in CBCT by using Student t test.
      RESULTS: For patients, the average dose differences in all dosimetric parameters
      of CBCT with DIR were smaller than those of CBCT with RR (eg, rectum; 0.54% for
      DIR vs 1.24% for RR). For the mCBCTs with DIR, the average dose differences in
      all dosimetric parameters were less than 1.0%. CONCLUSIONS: We evaluated the
      accuracy of the dose calculation in CBCT, mCBCT(MLT), and mCBCT(HM) with DIR for
      10 patients. The results showed that dose differences in D(mean), D(min), and
      D(max) in mCBCTs were within 1%, which were significantly better than those in
      CBCT, especially for the rectum (P<.05). Our results indicate that the mCBCT(MLT)
      and mCBCT(HM) can be useful for improving the dose calculation for adaptive
      radiation therapy.

PMID- 24685446
TI  - Spatiotemporal stability of Cu-ATSM and FLT positron emission tomography
      distributions during radiation therapy.
AB  - PURPOSE: In dose painting, in which functional imaging is used to define
      biological targets for radiation therapy dose escalation, changes in spatial
      distributions of biological properties during treatment can compromise the
      quality of therapy. The goal of this study was to assess the spatiotemporal
      stability of 2 potential dose painting targets--hypoxia and proliferation--in
      canine tumors during radiation therapy. METHODS AND MATERIALS: Twenty-two canine
      patients with sinonasal tumors (14 carcinoma and 8 sarcoma) were imaged before
      hypofractionated radiation therapy with copper(II)-diacetyl-bis(N4
      methylthiosemicarbazone) (Cu-ATSM) positron emission tomography/computed
      tomography (PET/CT) for hypoxia and 3'-deoxy-3'-(18)F-fluorothymidine (FLT)
      PET/CT for proliferation. The FLT scans were repeated after 2 fractions and the
      Cu-ATSM scans after 3 fractions. Midtreatment PET/CT images were deformably
      registered to pretreatment PET/CT images. Voxel-based Spearman correlation
      coefficients quantified the spatial stability of Cu-ATSM and FLT uptake
      distributions between pretreatment and midtreatment scans. Paired t tests
      determined significant differences between the patients' respective Cu-ATSM and
      FLT correlations coefficients. Standardized uptake value measures were also
      compared between pretreatment and midtreatment scans by use of paired t tests.
      RESULTS: Spatial distributions of Cu-ATSM and FLT uptake were stable through
      midtreatment for both sarcomas and carcinomas: the population mean +/- standard
      deviation in Spearman correlation coefficient was 0.88 +/- 0.07 for Cu-ATSM and
      0.79 +/- 0.13 for FLT. The patients' Cu-ATSM correlation coefficients were
      significantly higher than their respective FLT correlation coefficients (P=.001).
      Changes in Cu-ATSM SUV measures from pretreatment to midtreatment were histology
      dependent: carcinomas experienced significant decreases in Cu-ATSM uptake
      (P<.05), whereas sarcomas did not (P>.20). Both histologies experienced
      significant decreases in FLT uptake (P<.05). CONCLUSIONS: Spatial distributions
      of Cu-ATSM were very stable after a few fractions of radiation therapy. FLT
      spatial distributions were generally stable early in therapy, although they were
      significantly less stable than Cu-ATSM distributions. Canine tumors had
      significantly lower proliferative activity at midtreatment than at pretreatment,
      and they experienced histology-dependent changes in Cu-ATSM uptake.

PMID- 24685447
TI  - Prostate stereotactic ablative radiation therapy using volumetric modulated arc
      therapy to dominant intraprostatic lesions.
AB  - PURPOSE: To investigate boosting dominant intraprostatic lesions (DILs) in the
      context of stereotactic ablative radiation therapy (SABR) and to examine the
      impact on tumor control probability (TCP) and normal tissue complication
      probability (NTCP). METHODS AND MATERIALS: Ten prostate datasets were selected.
      DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion
      weighted magnetic resonance imaging. Four plans were produced for each dataset:
      (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3)
      boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose;
      and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning
      target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially
      prescribed 115% of the PTV(Prostate) prescription, and PTV(DIL) prescriptions
      were increased in 5% increments until organ-at-risk constraints were reached. TCP
      and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman
      models respectively. RESULTS: When treating the prostate alone, the median
      PTV(DIL) prescription was 125% (range: 110%-140%) of the PTV(Prostate)
      prescription. Median PTV(DIL) D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same
      PTV(DIL) prescriptions and similar PTV(DIL) median doses were possible when
      including the proxSV within the prescription. TCP depended on prostate alpha/beta
      ratio and was highest with an alpha/beta ratio = 1.5 Gy, where the additional TCP
      benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and
      was considered unacceptably high in 5 cases, which, when replanned with an
      emphasis on reducing maximum dose to 0.5 cm(3) of rectum (Dmax(0.5cc)), as well
      as meeting existing constraints, resulted in considerable rectal NTCP reductions.
      CONCLUSIONS: Boosting DILs in the context of SABR is technically feasible but
      should be approached with caution. If this therapy is adopted, strict rectal
      constraints are required including Dmax(0.5cc). If the alpha/beta ratio of
      prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by
      prescribing SABR to the whole prostate, without the need for DIL boosting.

PMID- 24685448
TI  - Pulmonary artery invasion, high-dose radiation, and overall survival in patients
      with non-small cell lung cancer.
AB  - PURPOSE: To investigate whether high-dose radiation to the pulmonary artery (PA)
      affects overall survival (OS) in patients with non-small cell lung cancer
      (NSCLC). METHODS AND MATERIALS: Patients with medically inoperable/unresectable
      NSCLC treated with definitive radiation therapy in prospective studies were
      eligible for this study. Pulmonary artery involvement was defined on the basis of
      pretreatment chest CT and positron emission tomography/CT fusion. Pulmonary
      artery was contoured according to the Radiation Therapy Oncology Group protocol
      1106 atlas, and dose-volume histograms were generated. RESULTS: A total of 100
      patients with a minimum follow-up of 1 year for surviving patients were enrolled:
      82.0% underwent concurrent chemoradiation therapy. Radiation dose ranged from 60
      to 85.5 Gy in 30-37 fractions. Patients with PA invasion of grade <=2, 3, 4, and
      5 had 1-year OS and median survival of 67% and 25.4 months (95% confidence
      interval [CI] 15.7-35.1), 62% and 22.2 months (95% CI 5.8-38.6), 90% and 35.8
      months (95% CI 28.4-43.2), and 50% and 7.0 months, respectively (P=.601). Two of
      the 4 patients with grade 5 PA invasion died suddenly from massive hemorrhage at
      3 and 4.5 months after completion of radiation therapy. Maximum and mean doses to
      PA were not significantly associated with OS. The V45, V50, V55, and V60 of PA
      were correlated significantly with a worse OS (P<.05). Patients with V45 >70% or
      V60 >37% had significantly worse OS (13.3 vs 37.9 months, P<.001, and 13.8 vs
      37.9 months, P=.04, respectively). CONCLUSIONS: Grade 5 PA invasion and PA volume
      receiving more than 45-60 Gy may be associated with inferior OS in patients with
      advanced NSCLC treated with concurrent chemoradiation.

PMID- 24685449
TI  - Heavy metal concentration in mangrove surface sediments from the north-west coast
      of South America.
AB  - Mangrove ecosystems are coastal estuarine systems confined to the tropical and
      subtropical regions. The Estero Salado mangrove located in Guayaquil, Ecuador,
      has suffered constant disturbances during the past 20 years, due to industrial
      wastewater release. However, there are no published data for heavy metals present
      in its sediments and the relationship with anthropogenic disturbance. In the
      present study, metal concentrations were evaluated in surface sediment samples of
      the mangrove, showing that B, Cd, Cu, Pb, Se, V, and Zn levels exceeded those
      declared in international environmental quality standards. Moreover, several
      metals (Pb, Sn, Cd, Ag, Mo, Zn and Ni) could be linked to the industrial
      wastewater present in the studied area. In addition, heavy metal levels detected
      in this mangrove are higher than previous reports on mangrove sediments
      worldwide, indicating that this mangrove ecosystem is one of the most disrupted
      on earth.

PMID- 24685450
TI  - Effects of the sandbar breaching on hydrobiological parameters and zooplankton
      communities in the Senegal River Estuary (West Africa).
AB  - This study describes the changes in hydrology, zooplankton communities and
      abundance in the Senegal River Estuary (SRE) before and after the breaching of
      the sandbar in October 2003. Samples were taken in 2003 at 3 stations located
      upstream (DI), in mid estuary (HY) and downstream (RM), and in 2005 at the same
      stations (RM becoming Old River Mouth: ORM), plus the new river mouth (NRM)
      resulting from the morphological evolution of the SRE. The study showed marked
      seasonal variations that affected the structure and distribution of zooplankton
      as well as major changes caused by the sandbar opening: increased marine
      influence throughout the whole SRE, changes in the horizontal gradients, arrival
      of euryhaline species and increase in meroplankton, in particular decapod larvae,
      transformation of the ORM area into a slackwater area with limited exchanges and
      the highest zooplankton numbers during high waters.

PMID- 24685451
TI  - Point-of-care ultrasound findings of acute pulmonary embolism: McConnell sign in
      emergency medicine.

PMID- 24685452
TI  - Bedside ultrasound AIDS identification and removal of cutaneous foreign bodies: a
      case series.
AB  - BACKGROUND: Soft tissue injury with a retained foreign body (FB) is a common
      emergency department (ED) complaint. Detection and precise localization of these
      foreign bodies is often difficult with traditional plain radiographic imaging or
      computed tomography (CT). CASE REPORT: We present three cases in which bedside
      ultrasound was used to identify and guide management of retained soft tissue
      foreign bodies. Comparison of ultrasound vs. plain radiography and CT, as well as
      techniques for FB identification and removal, are discussed. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Bedside ultrasound is an invaluable tool
      in the localization of foreign bodies in relation to other anatomic structures,
      and aids in the decision to remove them in the ED.

PMID- 24685453
TI  - Oblique-axis vs. short-axis view in ultrasound-guided central venous
      catheterization.
AB  - BACKGROUND: Ultrasound (US) guidance during central venous catheterization (CVC)
      reduces complications and improves success rates compared to landmark-guided
      techniques. A novel "oblique view" (US transducer held at approximately 45
      degrees  with respect to the target vessel) has been suggested to be superior to
      the standard short-axis approach usually used during US-guided CVC. OBJECTIVES:
      The purpose of this study was to compare the rates of posterior vessel wall
      puncture (PVWP) between the short-axis and oblique-axis approaches to US-guided
      CVC. METHODS: This was a prospective observational trial of emergency medicine
      residents and attending physicians, using gelatin models to simulate short-axis
      and oblique-axis US-guided CVC. Participants were blinded to the primary outcome
      of PVWP. Data collected included year in training/practice, number of central
      lines placed, time to successful "flash," and self-reported confidence of needle
      tip position using a Likert scale. After CVC simulation, models were
      deconstructed and inspected for PVWP. RESULTS: The rate of PVWP was 14.7% using
      short axis vs. 2.9% using oblique axis, resulting in a difference of 11.8% (95%
      confidence interval [CI] -4.7-28.3%, p = 0.10) and an odds ratio of 0.2 (95% CI
      0.004-1.79). This difference was not statistically significant (p = 0.10). Mean
      time to flash was 11.9 s using short axis, and 15.4 s using oblique axis (p =
      0.14). Confidence in needle tip location was 3.63 using short axis, and 4.58
      using oblique axis (p < 0.001). CONCLUSIONS: We found decreased PVWP using the
      oblique axis approach, though the difference was not statistically significant,
      and participants felt more confident in their needle tip location using the
      oblique axis view. Further research into the potential benefits of the oblique
      axis approach is warranted.

PMID- 24685454
TI  - Gas-forming liver abscess with pneumocardia.

PMID- 24685455
TI  - Molecular modeling of Gram-positive bacteria peptidoglycan layer, selected
      glycopeptide antibiotics and vancomycin derivatives modified with sugar moieties.
AB  - Proper understanding of the mechanisms of binding to Gram-positive bacteria cell
      wall layers-especially to the peptidoglycan (PG) layer, seems to be crucial for
      proper development of new drug candidates which are effective against these
      bacteria. In this work we have constructed two different models of the Gram
      positive bacteria PG layer: the layered and the scaffold models. PG
      conformational changes during geometry optimization, models relaxation, and
      molecular dynamics were described and discussed. We have found that the border
      surface of both PG layer models differs from the surface located away from the
      edge of models and the chains formed by disaccharide units prefer helix-like
      conformation. This curling of PG chains significantly affects the shape of
      antibiotic-accessible surface and the process is thus crucial for new drug
      development. Glycopeptide antibiotics effective against Gram-positive bacteria,
      such as vancomycin and its semisynthetic derivatives-oritavancin and telavancin,
      bind to d-alanyl-d-alanine stem termini on the peptidoglycan precursors of the
      cell wall. This binding inhibits cross-linking between the peptides and
      subsequently prevents cell wall synthesis. In this study some of the aspects of
      conformational freedom of vancomycin and restrictions from the modifications of
      vancomycin structure introduced into oritavancin and telavancin and five other
      vancomycin derivatives (with addition of 2-acetamido-2-deoxy-beta-d
      galactopyranosylamine, 2-acetamido-2-deoxy-beta-d-glucopyranosylamine, 1-amine-1
      deoxy-d-glucitol, 2-amino-2-deoxy-d-galactitol, or 2-amino-2-deoxy-d-glucitol to
      the C-terminal amino acid group in the vancomycin) are presented and discussed.
      The resulting molecular dynamics trajectories, root mean square deviation changes
      of aglycon and saccharide moieties as well as a comparative study of possible
      interactions with cyclic and chain forms of modified groups have been carried
      out, measured, and analyzed. Energetically advantageous conformations show close
      similarity to the structures known from the experimental data, but the diversity
      of others suggest very high conformational freedom of all modeled antibiotics and
      vancomycin derivatives. Alditol derivatives move closer to the peptidoglycan
      chain more easily but they also form intramolecular interactions more frequently
      than their homologous cyclic forms. One of the proposed derivatives seems to be a
      promising agent which is efficient in treatment of infections caused by Gram
      positive bacteria. 

PMID- 24685456
TI  - Stabilising metal(loid)s in soil with iron and aluminium-based products:
      microbial, biochemical and plant growth impact.
AB  - Four iron and aluminium-based products, including red mud (RM), hematite (Fe2O3),
      an iron-rich water treatment residual (Fe-WTR) and amorphous Al hydroxide (Al
      OH), were evaluated for their effectiveness at stabilising As and heavy metals
      (i.e. Cd, Cu, Pb, Zn) in a circumneutral contaminated soil [As (2105 mg kg(-1)),
      Cd (18 mg kg(-1)), Cu (264 mg kg(-1)), Pb (710 mg kg(-1)), Zn (522 mg kg(-1))].
      Treatment impacts on soil microbial and biochemical features (i.e. microbial
      biomass-C, microbial counts, 16S rRNA PCR-TTGE of culturable bacteria,
      dehydrogenase, urease and beta-glucosidase activity, Biolog derived parameters
      AWCD and richness) as well as bean (Phaseolus vulgaris) and wheat (Triticum
      vulgare) growth were also assessed. After 6 months equilibration, all the
      amendments (application rate 3% w/w) but RM reduced labile As while only Al-OH
      reduced the concentration of water-soluble heavy metals. Despite the highest
      bioavailability of contaminants, most of the soil microbial and biochemical
      features monitored (i.e. microbial biomass-C, total bacterial counts,
      dehydrogenase activity and AWCD) were significantly higher in the RM-soil. Bean
      germination was completely inhibited in RM-soil while wheat growth was similar to
      that of the control. The Al-OH treatment was best overall, promoting microbial
      abundance, diversity and activity while increasing bean and wheat growth and
      reducing As accumulated in plant shoots. Results suggest that Al-OH is a suitable
      candidate for field evaluations while the use of RM in the remediation of
      circumneutral or subalkaline contaminated soils should be reconsidered. 

PMID- 24685457
TI  - Exposure to vegetable variety in infants weaned at different ages.
AB  - The aim of the current study was to examine the effectiveness of different
      vegetable exposure methods (variety versus single taste) over a 9 day period in
      two groups of infants; those introduced to solids prior to the age of 5.5 months,
      and those introduced after 5.5 months. Sixty parent-infant dyads were recruited
      in South Birmingham, UK. Infants' acceptance of a novel vegetable (pea puree) was
      measured after a 9 day exposure period in the infants a week after they were
      first introduced to solid foods. During the exposure period half of each age
      group was given carrot every day, and the other half was given a variety pack of
      courgette, parsnip and sweet potato. A baseline measurement of the infants'
      acceptance of a vegetable (carrot) was taken prior to the exposure period. There
      was no difference between the groups in consumption of the baseline vegetable
      (carrot). There were no main effects of exposure group or age group on
      consumption of pea after the exposure period. There was, however, an interaction
      between the age of introduction and exposure group on consumption of the new
      vegetable (pea). In particular, infants weaned at 6 months in the single taste
      group ate significantly less pea puree than those in the variety group. These
      findings suggest that infants, who are weaned at 6 months or later, may benefit
      from being weaned onto a variety of tastes rapidly to ensure adequate exposure to
      taste. This study constitutes some of the first evidence to suggest that there
      may be a sensitive period for the acceptance of tastes between the ages of 4 and
      6 months. 

PMID- 24685458
TI  - Methadone safety: a clinical practice guideline from the American Pain Society
      and College on Problems of Drug Dependence, in collaboration with the Heart
      Rhythm Society.
AB  - Methadone is used for the treatment of opioid addiction and for treatment of
      chronic pain. The safety of methadone has been called into question by data
      indicating a large increase in the number of methadone-associated overdose deaths
      in recent years that has occurred in parallel with a dramatic rise in the use of
      methadone for chronic pain. The American Pain Society and the College on Problems
      of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned
      an interdisciplinary expert panel to develop a clinical practice guideline on
      safer prescribing of methadone for treatment of opioid addiction and chronic
      pain. As part of the guideline development process, the American Pain Society
      commissioned a systematic review of various aspects related to safety of
      methadone. After a review of the available evidence, the expert panel concluded
      that measures can be taken to promote safer use of methadone. Specific
      recommendations include the need to educate and counsel patients on methadone
      safety, use of electrocardiography to identify persons at greater risk for
      methadone-associated arrhythmia, use of alternative opioids in patients at high
      risk of complications related to corrected electrocardiographic QTc interval
      prolongation, careful dose initiation and titration of methadone, and diligent
      monitoring and follow-up. Although these guidelines are based on a systematic
      review, the panel identified numerous research gaps, most recommendations were
      based on low-quality evidence, and no recommendations were based on high-quality
      evidence. PERSPECTIVE: This guideline, based on a systematic review of the
      evidence on methadone safety, provides recommendations developed by a
      multidisciplinary expert panel. Safe use of methadone requires clinical skills
      and knowledge in use of methadone to mitigate potential risks, including serious
      risks related to risk of overdose and cardiac arrhythmias.

PMID- 24685459
TI  - Methadone overdose and cardiac arrhythmia potential: findings from a review of
      the evidence for an American Pain Society and College on Problems of Drug
      Dependence clinical practice guideline.
AB  - The number of deaths associated with methadone use increased dramatically in
      parallel with marked increases in its use, particularly for treatment of chronic
      pain. To develop a clinical guideline on methadone prescribing to reduce
      potential harms, the American Pain Society commissioned a review of various
      aspects related to methadone safety. This article summarizes evidence related to
      unintentional overdose due to methadone and harms related to cardiac arrhythmia
      potential. We searched Ovid MEDLINE, the Cochrane Library, and PsycINFO databases
      through January 2014 for studies assessing harms associated with methadone use;
      we judged 70 studies to be relevant and to meet inclusion criteria. The majority
      of studies on overdose and cardiac arrhythmia risk are observational and provide
      weak evidence on which to base clinical guidelines. In patients prescribed
      methadone for treatment of opioid dependence, data suggest that mortality
      benefits related to reduction in illicit drug use outweigh harms. Despite
      epidemiologic data showing marked increases in the numbers of methadone-related
      deaths that have been primarily attributed to increased use of methadone for
      chronic pain, evidence on methadone and mortality risk in this population has
      been somewhat contradictory. There is some evidence that recent initiation of
      methadone, psychiatric admissions, and concomitant use of benzodiazepines are
      associated with a higher risk for overdose. Evidence on cardiac risks is
      primarily limited to case reports of torsades de pointes, primarily in patients
      on high doses of methadone, and to studies showing an association between
      methadone use and prolongation of QTc intervals. Research is needed to understand
      the effectiveness of dosing methods, electrocardiogram monitoring, and other risk
      mitigation strategies in patients prescribed methadone. PERSPECTIVE: This
      systematic review synthesizes the evidence related to methadone use and risk for
      overdose and cardiac arrhythmia. Findings regarding the association between
      methadone use and QTc interval prolongation and risk factors for methadone
      associated overdose suggest potential targets for risk mitigation strategies,
      though research is needed to determine the effectiveness of such strategies at
      reducing adverse outcomes.

PMID- 24685460
TI  - Research gaps on methadone harms and comparative harms: findings from a review of
      the evidence for an American Pain Society and College on Problems of Drug
      Dependence clinical practice guideline.
AB  - Methadone-associated overdose deaths have dramatically increased. In order to
      inform an evidence-based clinical practice guideline to improve safety of
      methadone prescribing, the American Pain Society commissioned a systematic review
      on various aspects related to methadone safety. We searched Ovid MEDLINE,
      Cochrane Library, and PsycINFO databases through July 2012 to identify studies
      that addressed 1 or more of 17 Key Questions related to methadone safety; an
      update search was performed in 2014 for new studies related to methadone-related
      overdose and risks related to cardiac arrhythmias. A total of 168 studies met
      inclusion criteria for the review. The purpose of this article is to highlight
      critical research gaps in the literature related to methadone safety. These
      include lack of evidence on risk factors associated with methadone-overdose
      deaths and adverse events, limited evidence to evaluate the comparative mortality
      of methadone versus other opioids, insufficient evidence to fully understand the
      harms associated with methadone use during pregnancy, and insufficient evidence
      to determine effects of risk mitigation strategies such as electrocardiogram
      monitoring, strategies for managing patients with prolonged QTc intervals on
      screening, urine drug testing, alternative dosing regimens for initiation and
      titration of therapy, and timing of follow-up. Therefore, most guideline
      recommendations are based on weak evidence. More research is needed to guide safe
      methadone prescribing practices and decrease the adverse events associated with
      methadone. PERSPECTIVE: This article summarizes critical research gaps in the
      literature related to methadone safety, based on a systematic review commissioned
      by the American Pain Society. Critical research gaps were identified in a number
      of areas, highlighting the need for additional research to guide safer
      prescribing and risk mitigation strategies.

PMID- 24685461
TI  - Multifaceted chitin/poly(lactic-co-glycolic) acid composite nanogels.
AB  - Cyto-compatible, 80nm sized chitin/PLGA composite nanogels (chit/PLGA-comp NGs)
      were prepared by regeneration method and characterized. The multifaceted
      chit/PLGA-comp NGs were surface modified with Au, Fe3O4, CdTe/ZnTe-QDs and
      umbelliferone, respectively. 185nm sized Au-chit/PLGA-comp NGs, 170nm sized QD
      chit/PLGA-comp-NGs and 160nm sized Fe3O4-chit/PLGA-comp-NGs showed RF heating.
      The QD-chit/PLGA-comp-NGs and 180nm sized umb-chit/PLGA-comp-NGs were well
      uptaken by Escherichia coli, Staphylococcus aureus and Candida albicans. The
      chit/PLGA-comp NGs could be useful for microbial monitoring and RF application
      for cancer therapy. The preliminary data showed that multifaceted chit/PLGA-comp
      NGs could be useful for hyperthermia for cancer treatment and microbial labelling
      and imaging. 

PMID- 24685462
TI  - Extraction optimization of the polysaccharide from Adenophorae Radix by central
      composite design.
AB  - The central composite design (CCD) was applied to optimize the water extraction
      of the polysaccharide from Adenophorae Radix in the paper. The three variables of
      extraction temperature (X1), extraction time (X2) and ratio of water to raw
      material (X3) were investigated by single factor analysis first. Since the
      presence of active polysaccharides and the imperfect of its extraction, the
      purpose of the paper was to evaluate the effects of selected variables on the
      yield of polysaccharide, which was expected to obtain the maximum yield. By
      variance and regression analysis, the quadratic regression equation was
      established as a predicted model. The R(2) of 0.9825 indicated that the equation
      was well-fitted. The optimal conditions were 72.5 degrees C, 133min, 1:35 (g/mL)
      and the predicted maximum yield of the polysaccharide was 5.78%. The predicted
      value was verified in triplicates under the optimum conditions, which was 5.68%
      and well matched with the predictive yield. 

PMID- 24685463
TI  - Novel semi-IPN based on crosslinked carboxymethyl starch and clay for the in
      vitro release of theophylline.
AB  - A novel semi-interpenetrating polymer network (IPN) based on crosslinked
      carboxymethyl starch (CL-CMS) and montmorillonite (MMT) was prepared, where
      carboxymethylation occurs as a result of the reaction between native starch and
      monochloroacetic acid in isopropanol/water medium at 60 degrees C. The
      carboxymethyl starch is further crosslinked and made into a semi-IPN with MMT for
      the release of theophylline. The drug carrier was characterized using FTIR, XRD
      and surface analysis using SEM. Studies including physio-chemical analysis,
      swelling behavior, encapsulation efficiency, effect of MMT content, effect of
      ionic strength and in vitro drug release were carried out. Theophylline
      encapsulation of up to 74% was achieved and drug release was monitored in SGF (pH
      1.2) and SIF (pH 7.4). Results show that the matrix releases drug at a much
      faster rate in the basic medium than in the acidic medium, thereby holding the
      promise of developing the semi-IPN system as a potential candidate for the
      release of theophylline. 

PMID- 24685464
TI  - Effect of plasticizer on drug crystallinity of hydroxypropyl methylcellulose
      matrix film.
AB  - Effect of different hydrophilic plasticizers on drug crystallinity of
      hydroxypropyl methylcellulose (HPMC) matrix film was studied. HPMC films
      containing telmisartan using different plasticizers were prepared by casting
      method. Drug crystallinity in the films was examined using polarized light
      microscopy (PLM), scanning electron microscopy (SEM), and x-ray diffractometry
      (XRD) to describe their phase behavior/solid state miscibility/crystal growth and
      drug-polymer-plasticizer interaction. HPMC and plasticizer were compatible with
      the drug and no phase separation was observed upon solvent evaporation.
      Plasticized-HPMC contributed a major role in the significant inhibition of
      crystal growth of the drug in the film. The triethanolamine film produced a
      relatively smooth surface in comparison to the other films in the submicron
      level. The films have not shown any significant changes even after exposure to
      stress (40 degrees C/75% RH, 6 w). Triethanolamine as plasticizer brought about
      amorphization of telmisartan to the maximum extent in the film which is
      technologically more advantageous than the others owing to its anticipated better
      bioavailability. 

PMID- 24685465
TI  - Free radical scavenging activity and reducing power of Acacia nilotica wood
      lignin.
AB  - Nine different fractions of lignin extracted by alkali, hot water and organosolv
      methods from Acacia wood powder were assessed for antioxidants activity. Results
      indicated that methanolic lignin fraction had highest polyphenol content of
      393.30+/-9.2MUg/ml (GAE). The oraganosolv lignin with total phenols and phenolic
      hydroxyl group content exhibited significant antioxidant activity as compared to
      other lignin fractions. Antioxidant properties of acetone fractions revealed a
      high antiradical scavenging activity (<90%) with a simultaneous high ferric and
      molybdate ion reducing capacity. The influence of extraction methods on
      functional groups of lignin fractions was confirmed by analytical methods and
      Fourier transform infrared spectroscopy (FTIR) analysis. Whereas the phenolic
      content showed strong correlation with reducing capacity, the antiradical
      activity was moderately correlated with phenolic content. A high phenolic
      hydroxyl groups content of organosolv lignin fractions provides evidence for the
      presence of active therapeutic antioxidant compounds for their testing as
      potential value added products for cosmetics and pharmaceutical industries. 

PMID- 24685466
TI  - Probing the binding mode of psoralen to calf thymus DNA.
AB  - The binding properties between psoralen (PSO) and calf thymus DNA (ctDNA) were
      predicted by molecular docking, and then determined with the use of UV-vis
      absorption, fluorescence, circular dichroism (CD) and Fourier transform infrared
      (FT-IR) spectroscopy, coupled with DNA melting and viscosity measurements. The
      data matrix obtained from UV-vis spectra was resolved by multivariate curve
      resolution-alternating least squares (MCR-ALS) approach. The pure spectra and the
      equilibrium concentration profiles for PSO, ctDNA and PSO-ctDNA complex extracted
      from the highly overlapping composite response were obtained simultaneously to
      evaluate the PSO-ctDNA interaction. The intercalation mode of PSO binding to
      ctDNA was supported by the results from the melting studies, viscosity
      measurements, iodide quenching and fluorescence polarization experiments,
      competitive binding investigations and CD analysis. The molecular docking
      prediction showed that the specific binding most likely occurred between PSO and
      adenine bases of ctDNA. FT-IR spectra studies further confirmed that PSO
      preferentially bound to adenine bases, and this binding decreased right-handed
      helicity of ctDNA and enhanced the degree of base stacking with the preservation
      of native B-conformation. The calculated thermodynamic parameters indicated that
      hydrogen bonds and van der Waals forces played a major role in the binding
      process. 

PMID- 24685467
TI  - Antimicrobial susceptibility of Salmonella enterica isolates from healthy breeder
      and broiler flocks in Portugal.
AB  - Three hundred and thirty-three isolates representing 40 different serotypes of
      Salmonella enterica, recovered from environmental and faecal samples of breeder
      and broiler flocks from 2009 to 2011, were studied. Antimicrobial susceptibility
      was determined by measuring the minimal inhibitory concentration of 11
      antimicrobials using the agar dilution method. Salmonella Havana, S. Enteritidis
      and S. Mbandaka were the most common serotypes isolated from broiler flocks,
      while S. Enteritidis was the common isolate from breeder flocks. The frequency of
      non-wild-type Salmonella isolates (those with decreased susceptibility to the
      different antimicrobials) varied according to serotype. S. Mbandaka in broilers
      and S. Enteritidis in both breeders and broilers showed higher frequencies of
      reduced susceptibility to quinolones, but clinical resistance towards
      ciprofloxacin was not observed. Reduced susceptibility to sulfamethoxazole,
      tetracycline, ampicillin and streptomycin were common in Salmonella Typhimurium
      isolates. Two isolates of S. Havana from broilers were resistant to cefotaxime
      and phenotypically categorised as extended-spectrum beta-lactamase producers. The
      results presented in this study provide useful data on the antimicrobial
      susceptibility of different Salmonella serotypes and highlight the high diversity
      of multi-drug resistance patterns present.

PMID- 24685468
TI  - Using technology to find the secret places of the heart.

PMID- 24685470
TI  - Feline mycobacterial infections.
AB  - Mycobacteria of feline importance include (1) obligate pathogens (tuberculosis),
      (2) mycobacteria that are difficult to grow, so the environmental niche is
      unknown (feline leprosy syndrome), and (3) facultative pathogenic opportunistic
      saprophytes (non-tuberculous mycobacteriosis). Most cats present with cutaneous
      disease, although some have systemic involvement. Diagnosis is challenging
      because there are no pathognomonic histopathological changes and many
      mycobacteria fail to culture, so molecular diagnostics are required. Treatment
      can involve extended multidrug therapy and prognosis is variable. This article
      reviews the microbiology, clinical diagnosis, management and prognosis of feline
      mycobacterial infections. 

PMID- 24685469
TI  - Computed tomographic features of feline sino-nasal and sino-orbital
      aspergillosis.
AB  - Feline upper respiratory tract aspergillosis (URTA) occurs as two distinct
      anatomical forms, namely, sino-nasal aspergillosis (SNA) and sino-orbital
      aspergillosis (SOA). An emerging pathogen, Aspergillus felis, is frequently
      involved. The pathogenesis of URTA, in particular the relationship between the
      infecting isolate and outcome, is poorly understood. In this study, computed
      tomography was used to investigate the route of fungal infection and extension in
      16 cases (SNA n = 7, SOA n = 9) where the infecting isolate had been identified
      by molecular testing. All cases had nasal cavity involvement except for one cat
      with SNA that had unilateral frontal sinus changes. There was a strong
      association between the infecting species and anatomic form (P = 0.005). A.
      fumigatus infections remained within the sino-nasal cavity, while cryptic species
      infections were associated with orbital and paranasal soft-tissue involvement and
      with orbital lysis. Cryptic species were further associated with a mass in the
      nasal cavity, paranasal sinuses or nasopharynx. Orbital masses showed
      heterogeneous contrast enhancement, with central coalescing hypoattenuating foci
      and peripheral rim enhancement. Severe, cavitated turbinate lysis, typical of
      canine SNA, was present only in cats with SNA. These findings support the
      hypothesis that the nasal cavity is the portal of entry for fungal spores in
      feline URTA and that the route of extension to involve the orbit is via direct
      naso-orbital communication from bone lysis. Additionally, a pathogenic role for
      A. wyomingensis and a sinolith in a cat with A. udagawae infection are reported
      for the first time.

PMID- 24685471
TI  - Serological and virological detection of canine herpesvirus-1 in adult dogs with
      and without reproductive disorders.
AB  - Canine herpesvirus 1 (CaHV-1) is known to cause reproductive disorders in adult
      dogs and neonatal mortality in puppies. The seroprevalence of CaHV-1 has not been
      documented in Italy. Sera from 865 dogs were screened for CaHV-1 using a serum
      neutralization assay (SN). All CaHV-1 positive sera and 100 CaHV-1 negative sera
      were also tested using an in-house immunofluorescence (IF) test. Thirteen bitches
      with reproductive disorders and three bitches with no history of reproductive
      diseases were also examined clinically so that lesions associated with CaHV-1 and
      CaHV-1 DNA could be identified using PCR analysis of vaginal swabs. An overall
      seroprevalence of 14.6% was observed using SN, and 18.6% using IF. The
      correlation between SN and IF was moderate. The SN assay demonstrated a greater
      sensitivity than IF, with a few exceptions. None of the vaginal swabs tested
      positive for CaHV-1 DNA. The differences in the seropositivity rates between SN
      and IF were not statistically significant (P = 0.16). Using the SN test as the
      reference standard, the sensitivity and specificity of IF were 29% and 95%,
      respectively. These results suggest that CaHV-1 is common in canine populations
      and could pose a threat to neonatal survival and canine fertility in breeding
      kennels in Italy. Vaccination of breeding bitches should be recommended if there
      is a history of reproductive disorders.

PMID- 24685472
TI  - Epidemiology of reproductive pathogens in semi-intensive lamb-producing flocks in
      North-West Spain: a comparative serological study.
AB  - The aim of this study was to better understand the epidemiology of five major
      reproductive pathogens in semi-intensive lamb-producing flocks in North-West
      Spain. Two thousand four hundred serum samples were collected from 44 flocks, and
      several factors were studied to assess their influence on seropositivity. Farms
      that tested seropositive for more than one pathogen were common (84.1%), but
      seroprevalence was high only for Toxoplasma gondii (38.1%), and low for the other
      four pathogens, namely, Neospora caninum (5.5%), Coxiella burnetii (4.0%),
      Chlamydia abortus (3.9%) and Pestivirus (2.3%). Farm level exposure was highest
      for T. gondii and N. caninum (100% and 72.7%, respectively). For both of these
      pathogens, and for C. burnetii, seropositivity was associated with age and area.
      Farm level exposure was lowest for Pestivirus and C. abortus (13.6% and 18.2%,
      respectively), and, for the latter, seropositivity was principally related to
      flock size.

PMID- 24685473
TI  - Duplication of the lower third of the internal jugular vein--case report and
      surgical implications.
AB  - Duplication of the internal jugular vein is rare with a reported incidence of
      0.4%. Most are located in the upper third and are almost always unilateral,
      duplication of the lower third is less common. In the case presented the vein
      divided above the omohyoid muscle with one branch passing superficial and the
      other deep to the muscle. Failure to recognise this anomaly could result in
      iatrogenic damage to the superficial branch in particular, with brisk and
      unexpected haemorrhage during neck dissection. 

PMID- 24685474
TI  - Fracture of the clivus as an unusual complication of LeFort I osteotomy: case
      report.
AB  - LeFort I osteotomy is a standard technique for the surgical correction of
      dentofacial deformities. Despite its low morbidity, it can lead to various
      complications at the base of the skull. We report the case of a fractured clivus
      as an unusual complication. 

PMID- 24685475
TI  - Evidence based management of Bell's palsy.
AB  - Bell's palsy (idiopathic facial paralysis) is caused by the acute onset of lower
      motor neurone weakness of the facial nerve with no detectable cause. With a
      lifetime risk of 1 in 60 and an annual incidence of 11-40/100,000 population, the
      condition resolves completely in around 71% of untreated cases. In the remainder
      facial nerve function will be impaired in the long term. We summarise current
      published articles regarding early management strategies to maximise recovery of
      facial nerve function and minimise long-term sequelae in the condition. 

PMID- 24685476
TI  - Use of the Alexis ring retractor in oral and maxillofacial surgery.

PMID- 24685477
TI  - Scaffold preferences of mesenchymal stromal cells and adipose-derived stem cells
      from green fluorescent protein transgenic mice influence the tissue engineering
      of bone.
AB  - We have analysed the growth and differentiation of mesenchymal stromal cells
      (MSC) from bone marrow, and of adipose derived stem cells (ASC) from murine
      abdominal fat tissue, of green fluorescent protein (GFP) transgenic animals grown
      directly on two types of hydroxyapatite ceramic bone substitutes. BONITmatrix(r)
      and NanoBone(r) have specific mechanical and physiochemical properties such as
      porosity and an inner surface that influence cellular growth. Both MSC and ASC
      were separately seeded on 200mg of each biomaterial and cultured for 3 weeks
      under osteogenic differentiation conditions. The degree of mineralisation was
      assessed by alizarin red dye and the specific alkaline phosphatase activity of
      the differentiated cells. The morphology of the cells was examined by scanning
      electron microscopy and confocal microscopy. The osteoblastic phenotype of the
      cells was confirmed by analysing the expression of bone-specific genes (Runx2,
      osteocalcin, osteopontin, and osteonectin) by semiquantitative reverse
      transcriptase polymerase chain reaction (PCR). Comparison of BONITmatrix(r) and
      NanoBone(r) showed cell type-specific preferences in terms of osteogenic
      differentiation. MSC-derived osteoblast-like cells spread optimally on the
      surface of NanoBone(r) but not BONITmatrix(r) granules. In contrast
      BONITmatrix(r) granules conditioned the growth of osteoblast-like cells derived
      from ASC. The osteoblastic phenotype of the cultured cells on all matrices was
      confirmed by specific gene expression. Our results show that the in vitro growth
      and osteogenic differentiation of murine MSC or ASC of GFP transgenic mice are
      distinctly influenced by the ceramic substratum. While NanoBone(r) granules
      support the proliferation and differentiation of murine MSC isolated from bone
      marrow, the growth of murine ASC is supported by BONITmatrix(r) granules.
      NanoBone(r) is therefore recommended for use as scaffold in tissue engineering
      that requires MSC, whereas ASC can be combined with BONITmatrix(r) for in vitro
      bone engineering.

PMID- 24685478
TI  - Effects of hormone replacement therapy on the rate of recurrence in endometrial
      cancer survivors: a meta-analysis.
AB  - BACKGROUND: To quantify the effect of hormone replacement therapy (HRT) on the
      recurrence in endometrial cancer (EC) survivors through a meta-analysis. METHODS:
      A systematic literature review was conducted through October 2013 and included
      studies reporting estimates of effect size for the relationship between HRT use
      and the risk of EC recurrence. Study design features that may affect the
      selection of participants, the detection of EC recurrence and manuscript
      publication were assessed. If there was no significant statistical heterogeneity
      across studies, then a fixed effects model was used to obtain pooled estimates
      for the effect of HRT use on EC recurrence by combining study-specific estimates
      of the odds ratio (OR). RESULTS: One randomised trial and five observational
      studies included 896 EC survivors who used HRT and 1079 non-users. Over the
      combined study period, 19 of the 896 HRT users experienced recurrence, whereas 64
      of the 1079 controls did. The meta-analysis based on the fixed effects model
      indicates no significant increase in the risk of recurrence in EC survivors using
      HRT relative to the control group (OR: 0.53; 95% confidence interval: 0.30-0.96,
      I(2)=49.0). This pattern was also observed in the subgroup analysis for the stage
      and type of HRT. There was no evidence of any publication bias. CONCLUSIONS:
      Although based mainly on observational studies, the literature does not provide
      support for a positive relationship between HRT use and the risk of EC
      recurrence. Future research should verify this relationship through randomised
      controlled trials over a longer term.

PMID- 24685479
TI  - Rapamycin-mediated CD36 translational suppression contributes to alleviation of
      hepatic steatosis.
AB  - Rapamycin, a mammalian target of rapamycin (mTOR)-specific inhibitor, has the
      effect of anti-lipid deposition on non-alcoholic fatty liver disease (NAFLD), but
      the mechanisms with which rapamycin alleviates hepatic steatosis are not fully
      disclosed. CD36 is known to facilitate long-chain fatty acid uptake and
      contribute to NAFLD progression. Hepatic CD36 expression is closely associated
      with hepatic steatosis, while mTOR pathway is involved in CD36 translational
      control. This study was undertaken to investigate whether rapamycin alleviates
      hepatic steatosis via the inhibition of mTOR pathway-dependent CD36 translation.
      Human hepatoblastoma HepG2 cells were treated with palmitate and C57BL/6J mice
      were fed with high fat diet (HFD) to induce hepatic steatosis. Hepatic CD36
      protein expression was significantly increased with lipid accumulation in
      palmitate-treated HepG2 cells or HFD-fed C57BL/6J mice. Rapamycin reduced hepatic
      steatosis and CD36 protein expression, but it had no influence on CD36 mRNA
      expression. Rapamycin had no effect on CD36 protein stability, but it
      significantly decreased CD36 translational efficiency. We further confirmed that
      rapamycin inhibited the phosphorylation of mTOR and its downstream translational
      regulators including p70 ribosomal protein S6 kinase (p70S6K), eukaryotic
      initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic initiation factor
      4E (eIF4E). This study demonstrates that rapamycin inhibits hepatic CD36
      translational efficiency through the mTOR pathway, resulting in reduction of CD36
      protein expression and alleviation of hepatic steatosis.

PMID- 24685480
TI  - CUEDC2 interacts with heat shock protein 70 and negatively regulates its
      chaperone activity.
AB  - Recently studies have revealed that CUEDC2, a CUE domain-containing protein,
      plays critical roles in many biological processes, such as cell cycle,
      inflammation and tumorigenesis. In this study, to further explore the function of
      CUEDC2, we performed affinity purification combined with mass spectrometry
      analysis to identify its interaction proteins, which led to the identification of
      heat shock protein 70 (HSP70). We confirmed the interaction between CUEDC2 and
      HSP70 in vivo by co-immunoprecipitation assays. Mapping experiments revealed that
      CUE domain was required for their binding, while the PBD and CT domains of HSP70,
      mediated the interaction with CUEDC2. The intracellular Luciferase refolding
      assay indicated that CUEDC2 could inhibit the chaperone activity of HSP70.
      Together, our results identify HSP70 as a novel CUEDC2 interaction protein and
      suggest that CUEDC2 might play important roles in regulating HSP70 mediated
      stress responses.

PMID- 24685481
TI  - Fatty acid composition in matrix vesicles and in microvilli from femurs of
      chicken embryos revealed selective recruitment of fatty acids.
AB  - Hypertrophic chondrocytes participate in matrix mineralization by releasing
      matrix vesicles (MVs). These MVs, by accumulating Ca(2+) and phosphate initiate
      the formation of hydroxyapatite. To determine the types of lipids essential for
      mineralization, we analyzed fatty acids (FAs) in MVs, microvilli and in membrane
      fractions of chondrocytes isolated from femurs of chicken embryos. The FA
      composition in the MVs was almost identical to that in microvilli, indicating
      that the MVs originated from microvilli. These fractions contained more
      monounsaturated FAs especially oleic acid than in membrane homogenates of
      chondrocytes. They were enriched in 5,8,11-eicosatrienoic acid (20:3n-9), in
      eicosadienoic acid (20:2n-6), and in arachidonic acid (20:4n-6). In contrast,
      membrane homogenates from chondrocytes were enriched in 20:1n-9, 18:3n-3, 22:5n-3
      and 22:5n-6. Due to their relatively high content in MVs and to their selective
      recruitment within microvilli from where MV originate, we concluded that 20:2n-6
      and 20:3n-9 (pooled values), 18:1n-9 and 20:4n-6 are essential for the biogenesis
      of MVs and for bone mineralization. 

PMID- 24685482
TI  - Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in
      zebrafish.
AB  - Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial
      hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the
      angiopoietin-like family, the vascular endothelial growth factor family that is
      structurally similar to angiopoietins and is known for a regulator of lipid and
      glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to
      defect in liver development in the vertebrates. We report here that angptl3 is
      primarily expressed in the zebrafish developing liver and that morpholino (MO)
      knockdown of Angptl3 reduces the size of the developing liver, which is caused by
      suppression of cell proliferation, but not by enhancement of apoptosis. However,
      MO knockdown of Angptl3 did not alter angiogenesis in the developing liver.
      Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia
      phenotype that is characteristic of FHBL2 in humans. Together, our findings
      propose a novel role for Angptl3 in liver cell proliferation and maintenance
      during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good
      model for understanding the pathophysiology of FHBL2. 

PMID- 24685483
TI  - Aging differentially alters the expression of angiogenic genes in a tissue
      dependent manner.
AB  - Organ functions are altered and impaired during aging, thereby resulting in
      increased morbidity of age-related diseases such as Alzheimer's disease,
      diabetes, and heart failure in the elderly. Angiogenesis plays a crucial role in
      the maintenance of tissue homeostasis, and aging is known to reduce the
      angiogenic capacity in many tissues. Here, we report the differential effects of
      aging on the expression of angiogenic factors in different tissues, representing
      a potentially causes for age-related metabolic disorders. PCR-array analysis
      revealed that many of angiogenic genes were down-regulated in the white adipose
      tissue (WAT) of aged mice, whereas they were largely up-regulated in the skeletal
      muscle (SM) of aged mice compared to that in young mice. Consistently, blood
      vessel density was substantially reduced and hypoxia was exacerbated in WAT of
      aged mice compared to that in young mice. In contrast, blood vessel density in SM
      of aged mice was well preserved and was not different from that in young mice.
      Moreover, we identified that endoplasmic reticulum (ER) stress was strongly
      induced in both WAT and SM during aging in vivo. We also found that ER stress
      significantly reduced the expression of angiogenic genes in 3T3-L1 adipocytes,
      whereas it increased their expression in C2C12 myotubes in vitro. These results
      collectively indicate that aging differentially affects the expression of
      angiogenic genes in different tissues, and that aging-associated down-regulation
      of angiogenic genes in WAT, at least in part through ER stress, is potentially
      involved in the age-related adipose tissue dysfunction. 

PMID- 24685484
TI  - Neuronal cells but not muscle cells are resistant to oxidative stress mediated
      protein misfolding and cell death: role of molecular chaperones.
AB  - Our recent study in a mouse model of familial-Amyotrophic Lateral Sclerosis (f
      ALS) revealed that muscle proteins are equally sensitive to misfolding as spinal
      cord proteins despite the presence of low mutant CuZn-superoxide dismutase, which
      is considered to be the key toxic element for initiation and progression of f
      ALS. More importantly, we observed differential level of heat shock proteins
      (Hsp's) between skeletal muscle and spinal cord tissues prior to the onset and
      during disease progression; spinal cord maintains significantly higher level of
      Hsp's compared to skeletal muscle. In this study, we report two important
      observations; (i) muscle cells (but not neuronal cells) are extremely vulnerable
      to protein misfolding and cell death during challenge with oxidative stress and
      (ii) muscle cells fail to mount Hsp's during challenge unlike neuronal cells.
      These two findings can possibly explain why muscle atrophy precedes the death of
      motor neurons in f-ALS mice. 

PMID- 24685485
TI  - Evidence-based medicine reviews of hand and upper extremity.

PMID- 24685486
TI  - Angiosarcoma of the face and scalp: effective systemic treatment in the older
      patient.
AB  - BACKGROUND: Angiosarcoma of the face and scalp, though rare, frequently affects
      older people and the prognosis is poor. Due to its rarity, optimal management of
      advanced disease with chemotherapy has been difficult to define. OBJECTIVE: This
      is a retrospective review of patients treated at the Royal Marsden Hospital
      (RMH), looking at chemotherapy regimens, toxicity profile and treatment outcome
      in this elderly population over the last 20years. MATERIALS AND METHODS: Detailed
      clinical-pathologic data were collected on patients treated for head and neck
      angiosarcoma at RMH between 1992 and 2011. RESULTS: Thirteen patients (median
      age: 79years) were eligible for analysis. The majority (92.3%) received taxanes
      with a response rate of 83.3% and median progression-free survival (PFS) of
      7months. Although the main toxicities were lethargy and peripheral neuropathy, a
      median number of 6 cycles of paclitaxel were administered. Doxorubicin was used
      in 57% of patients (median number of cycles: 3) with a response rate of 50%
      (median PFS: 3months). Cardiotoxicity occurred in 2 out of 7 cases and led to
      discontinuation of treatment. Overall, 57.1% of patients received chemotherapy at
      least 2 lines of chemotherapy. There were no deaths attributable to systemic
      treatment. CONCLUSIONS: Advanced angiosarcoma of face and scalp can be controlled
      with multiple lines of chemotherapy, consisting primarily of taxanes as well as
      anthracyclines. Old age should not preclude systemic therapy although safety and
      quality of life issues deserve careful consideration.

PMID- 24685487
TI  - Undisclosed chemicals--implications for risk assessment: a case study from the
      mining industry.
AB  - Many of the chemicals used in industry can be hazardous to human health and the
      environment, and some formulations can have undisclosed ingredients and hazards,
      increasing the uncertainty of the risks posed by their use. The need for a better
      understanding of the extent of undisclosed information in chemicals arose from
      collecting data on the hazards and exposures of chemicals used in typical mining
      operations (copper, platinum and coal). Four main categories of undisclosed
      chemicals were defined (incomplete disclosure; chemicals with unspecific
      identities; relative quantities of ingredients not stated; and trade secret
      ingredients) by reviewing material safety data sheet (MSDS) omissions in previous
      studies. A significant number of chemicals (20% of 957 different chemicals)
      across the three sites had a range of undisclosed information, with majority of
      the chemicals (39%) having unspecific identities. The majority of undisclosed
      information was found in commercially available motor oils followed by cleaning
      products and mechanical maintenance products, as opposed to reagents critical to
      the main mining processes. All three types of chemicals had trade secrets,
      unspecific chemical identities and incomplete disclosures. These types of
      undisclosed information pose a hindrance to a full understanding of the hazards,
      which is made worse when combined with additional MSDS omissions such as acute
      toxicity endpoints (LD50) and/or acute aquatic toxicity endpoints (LC50), as well
      as inadequate hazard classifications of ingredients. The communication of the
      hazard information in the MSDSs varied according to the chemical type, the
      manufacturer and the regulations governing the MSDSs. Undisclosed information can
      undermine occupational health protection, compromise the safety of workers in
      industry, hinder risk assessment procedures and cause uncertainty about future
      health. It comes down to the duty of care that industries have towards their
      employees. With a wide range of chemicals increasingly used, there is a balance
      that needs to be reached between disclosure requirements, trade secret provisions
      and definitions of hazardous ingredients for market needs, and the information
      required to protect the health of their workers. 

PMID- 24685488
TI  - Influence of a municipal solid waste landfill in the surrounding environment:
      toxicological risk and odor nuisance effects.
AB  - The large amounts of treated waste materials and the complex biological and
      physicochemical processes make the areas in the proximity of landfills vulnerable
      not only to emissions of potential toxic compounds but also to nuisance such as
      odor pollution. All these factors have a dramatic impact in the local environment
      producing environmental quality degradation. Most of the human health problems
      come from the landfill gas, from its non-methanic volatile organic compounds and
      from hazardous air pollutants. In addition several odorants are released during
      landfill operations and uncontrolled emissions. In this work we present an
      integrated risk assessment for emissions of hazard compounds and odor nuisance,
      to describe environmental quality in the landfill proximity. The study was based
      on sampling campaigns to acquire emission data for polychlorinated dibenzo-p
      dioxins and dibenzofurans, dioxin-like polychlorobiphenyls, polycyclic aromatic
      hydrocarbons, benzene and vinyl chloride monomer and odor. All concentration
      values in the emissions from the landfill were measured and used in an air
      dispersion model to estimate maximum concentrations and depositions in
      correspondence to five sensitive receptors located in proximity of the landfill.
      Results for the different scenarios and cancer and non-cancer effects always
      showed risk estimates which were orders of magnitude below those accepted from
      the main international agencies (WHO, US EPA). Odor pollution was significant for
      a limited downwind area near the landfill appearing to be a significant risk
      factor of the damage to the local environment. 

PMID- 24685489
TI  - Methylmercury exposure and neurological outcomes in Taiji residents accustomed to
      consuming whale meat.
AB  - Methylmercury (MeHg) is a major environmental neurotoxicant that causes damage to
      the central nervous system. In Japan, industrial emission of MeHg has resulted in
      MeHg intoxication in Minamata and Niigata, the so-called Minamata disease. Humans
      are exposed to MeHg derived from natural sources, primarily fish and fish
      predators. Therefore, MeHg continues to be an environmental risk to human health,
      particularly in susceptible populations that frequently consume substantial
      amounts of fish or fish predators such as whale. This study aimed to investigate
      the health effects of MeHg exposure in adults. The subjects were 194 residents
      (117 males, 77 females; age 20-85 years) who resided in the coastal town of
      Taiji, the birthplace of traditional whaling in Japan. We analyzed hair for
      mercury content and performed detailed neurological examinations and dietary
      surveys. Audiometry, magnetic resonance imaging, and electromyography were
      performed to diagnose neurological defects. Whole blood mercury and selenium (Se)
      levels were measured in 23 subjects. The geometric mean of the hair mercury
      levels was 14.9 MUg/g. Twelve subjects revealed hair mercury levels >50 MUg/g
      (NOAEL) set by WHO. Hair mercury levels significantly correlated with daily whale
      meat intake. These results suggested that residents in Taiji were highly exposed
      to MeHg by ingesting MeHg-contaminated whale meat. Multivariate regression
      analysis demonstrated no significant correlations between hair mercury levels and
      neurological outcomes, whereas some of the findings significantly correlated with
      age. A significantly positive correlation between whole blood mercury and Se
      levels was observed and the whole blood mercury/Se molar ratios of all subjects
      were <1. These findings suggested that sufficient Se intake might be one of
      causes of the absence of adverse effects of MeHg exposure in this study.

PMID- 24685490
TI  - An uninvited guest.

PMID- 24685491
TI  - Five-fold increase in use of inhaled corticosteroids over 18 years in the general
      adult population in west Sweden.
AB  - INTRODUCTION: Asthma medication was increasingly used during the second part of
      the past century. There are few detailed data from population studies on use of
      asthma medication. The current study aimed to determine the use and determinants
      of asthma medication in West Sweden and to assess changes during the last two
      decades. METHODS: From a random population sample participating in a survey on
      respiratory symptoms, 2000 individuals were randomly selected for clinical
      examinations and structured interviews, 1172 participated. All subjects reporting
      asthma (n = 1524) were also invited, and 834 participated. In total, 964 subjects
      with asthma participated. Asthma medication use was assessed in the general
      population and among two severity categories of asthma: multi-symptom asthma
      (MSA) and "other" asthma (having fewer symptoms). Current data, from 2010, was
      compared with data from 1992. RESULTS: Asthma medication was used by 11% of the
      population, 4.4% used ICS with concurrent use of LABA, 3.3% used ICS without
      LABA, while 3.2% only used SABA. Compared with 1992, the prevalence of asthma
      medication use had increased with 54%, and use of ICS had increased from 1.5% to
      7.7%. CONCLUSION: Subjects with MSA reported using asthma medication more
      frequently and at higher doses, and a higher proportion used ICS.A shift in
      asthma medication use has occurred since 1992, with increased use of ICS and
      decreased use of SABA only, implying better asthma control on a population level.
      Multi-symptom asthma should alert the treating physician to consider under
      medication and/or poor treatment adherence.

PMID- 24685492
TI  - Potential role of pentosidine on susceptibility to small airway closure in
      elderly and smoking asthma.
AB  - BACKGROUND: Small airway closure in asthma is determined by a complex interaction
      of structural and functional characteristics including lung elastic recoil.
      Recently, we determined that loss of elastic recoil might be attributable to
      pentosidine level in the airways. This study was designed to investigate the
      influences of aging and smoking on small airway closure in asthma. METHODS: Sixty
      one patients with asthma (20 non-smoking young adult, 23 non-smoking elderly, and
      18 smoking young adult) and 36 control subjects (12 non-smoking young adult, 11
      non-smoking elderly, and 13 smoking young adult) were included. We assessed
      airway responses during methacholine provocation and calculated the closing
      index. In addition, we measured pentosidine levels in induced sputum from all
      study subjects. RESULTS: Pentosidine levels in induced sputum were markedly
      higher in asthmatic patients than in controls. In control subjects, the
      intergroup differences in pentosidine level among 3 subgroups were significant.
      Similarly, pentosidine levels were significantly higher in non-smoking elderly
      and smoking young adult asthmatics than in non-smoking young adult asthmatics.
      There was no significant difference in pentosidine levels between non-smoking
      elderly and smoking young adult asthmatics. The closing index was also
      significantly higher in non-smoking elderly and smoking young adult asthmatics
      than in non-smoking young adult asthmatics. Moreover, pentosidine levels in non
      smoking elderly and smoking young adult asthmatics were closely correlated with
      closing index. CONCLUSIONS: We determined the correlation of pentosidine level
      with susceptibility to small airway closure in elderly and smoking asthmatics.
      Our results might facilitate the understanding of elderly and smoking asthma.

PMID- 24685493
TI  - Monte Carlo simulations of dose distributions with necrotic tumor targeted
      radioimmunotherapy.
AB  - Radio-resistant hypoxic tumor cells are significant contributors to the
      locoregional recurrences and distant metastases that mark failure of
      radiotherapy. Due to restricted tissue oxygenation, chronically hypoxic tumor
      cells frequently become necrotic and thus there is often an association between
      chronically hypoxic and necrotic tumor regions. This simulation study is the
      first in a series to determine the feasibility of hypoxic cell killing after
      first targeting adjacent areas of necrosis with either an alpha- or beta-emitting
      radioimmunoconjugate. 

PMID- 24685494
TI  - Synthesis of [11C]PBR170, a novel imidazopyridine, for imaging the translocator
      protein with PET.
AB  - The translocator protein (TSPO) ligand 2-(6,8-dichloro-2-(4
      ethoxyphenyl)imidazo[1,2-a]pyridin-3-yl)-N-(2-fluoropyridin-3-yl)-N
      methylacetamide (PBR170), is a novel imidazopyridineacetamide with high affinity
      (2.6 nm) and selectivity for the TSPO. The synthesis of [(11)C]PBR170 was
      accomplished by N-methylation of the corresponding desmethyl precursor with
      [(11)C]methyl iodide in the presence of sodium hydroxide in dimethylformamide.
      [(11)C]PBR170 was produced in 30-45% radiochemical yield (decay-corrected, based
      on [(11)C]methyl iodide) with a radiochemical purity >98% and a specific activity
      of 90-190 GBq/MUmol after 35 min of synthesis time.

PMID- 24685495
TI  - Elemental characterization of coal, fly ash, and bottom ash using an energy
      dispersive X-ray fluorescence technique.
AB  - A total of 18 elements viz. Si, Al, Fe, Ca, Mg, K, Na, Sr, V, Zn, Mn, Cr, Cu, Pb,
      Ni, Co, As and Cd were analyzed in coal, fly ash and bottom ash samples collected
      across India using an EDXRF technique. Various indices such as element enrichment
      ratio, enrichment factor (with respect to crustal average) and mineral
      composition were calculated. Around 95% of mass was reconstructed using the
      concentration of elements in this study for fly and bottom ash. 

PMID- 24685496
TI  - A comparative study on component volumes from outer to inner dental enamel in
      relation to enamel tufts.
AB  - BACKGROUND AND AIM: Dental enamel presents marked mechanical properties gradients
      from outer to inner enamel, a region lacking component volumes profiles. Tufts,
      structures of inner enamel, have been shown to play a role in enamel resilience.
      We aimed at comparing component volumes from inner to outer enamel in relation to
      enamel tufts. MATERIALS AND METHODS: Transversal ground sections from the
      cervical half of unerupted human third molars (n=10) were prepared and
      histological points were selected along transversal lines (extending from
      innermost to outer enamel) traced across tufts and adjacent control areas without
      tufts. Component volumes were measured at each histological point. RESULTS:
      Component volumes ranges were: 70.6-98.5% (mineral), 0.02-20.78% (organic), 3.8
      9.8% (total water), 3-9% (firmly bound water), and 0.02-3.3% (loosely bound
      water). Inner enamel presented the lowest mineral volumes and the highest non
      mineral volumes. Mineral, water and organic contents differed as a function of
      the distance from innermost enamel but not between the tuft and control lines.
      Tufts presented opaqueness in polarizing microscopy (feature of fracture lines).
      Organic volume gradient correlated with a relatively flat profile of loosely
      bound water. Inner, but not outer enamel, rehydrated after air-dried enamel was
      heated to 50 degrees C and re-exposed to room conditions, as predicted by the
      organic/water gradient profiles. CONCLUSIONS: Component volumes vary markedly
      from outer to inner enamel, but not between areas with or without tufts (that
      behave like fracture lines under polarizing microscopy).

PMID- 24685497
TI  - Multilocus approach to clarify species status and the divergence history of the
      Bemisia tabaci (Hemiptera: Aleyrodidae) species complex.
AB  - The sweet potato whitefly, Bemisia tabaci, is a highly differentiated species
      complex. Despite consisting of several morphologically indistinguishable entities
      and frequent invasions on all continents with important associated economic
      losses, the phylogenetic relationships, species status, and evolutionary history
      of this species complex is still debated. We sequenced and analyzed one
      mitochondrial and three single-copy nuclear genes from 9 of the 12 genetic groups
      of B. tabaci and 5 closely related species. Bayesian species delimitation was
      applied to investigate the speciation events of B. tabaci. The species statuses
      of the different genetic groups were strongly supported under different prior
      settings and phylogenetic scenarios. Divergence histories were estimated by a
      multispecies coalescence approach implemented in (*)BEAST. Based on mitochondrial
      locus, B. tabaci was originated 6.47 million years ago (MYA). Nevertheless, the
      time was 1.25MYA based on nuclear loci. According to the method of approximate
      Bayesian computation, this difference is probably due to different degrees of
      migration among loci; i.e., although the mitochondrial locus had differentiated,
      gene flow at nuclear loci was still possible, a scenario similar to parapatric
      mode of speciation. This is the first study in whiteflies using multilocus data
      and incorporating Bayesian coalescence approaches, both of which provide a more
      biologically realistic framework for delimiting species status and delineating
      the divergence history of B. tabaci. Our study illustrates that gene flow during
      species divergence should not be overlooked and has a great impact on divergence
      time estimation. 

PMID- 24685498
TI  - Phylogenetic analysis of mitochondrial genome sequences indicates that the cattle
      tick, Rhipicephalus (Boophilus) microplus, contains a cryptic species.
AB  - Cattle ticks of the subgenus Rhipicephalus (Boophilus) are major agricultural
      pests worldwide, causing billions of dollars in losses annually. Rhipicephalus
      (Boophilus) annulatus and R. microplus are the most well-known and widespread
      species, and a third species, R. australis, was recently reinstated for 'R.
      microplus' from Australia and parts of Southeast Asia. We use mitochondrial
      genome sequences to address the phylogenetic relationships among the species of
      the subgenus Boophilus. We sequenced the complete or partial mitochondrial
      genomes of R. annulatus, R. australis, R. kohlsi, R. geigyi, and of three
      geographically disparate specimens of R. microplus from Brazil, Cambodia and
      China. Phylogenetic analyses of mitochondrial genomes, as well as cox1 and 16S
      rRNA sequences, reveals a species complex of R. annulatus, R. australis, and two
      clades of R. microplus, which we call the R. microplus complex. We show that
      cattle ticks morphologically identified as R. microplus from Southern China and
      Northern India (R. microplus clade B) are more closely related to R. annulatus
      than other specimens of R. microplus s.s. from Asia, South America and Africa (R.
      microplus clade A). Our analysis suggests that ticks reported as R. microplus
      from Southern China and Northern India are a cryptic species. This highlights the
      need for further molecular, morphological and crossbreeding studies of the R.
      microplus complex, with emphasis on specimens from China and India. We found that
      cox1 and, to a lesser extent, 16S rRNA were far more successful in resolving the
      phylogenetic relationships within the R. microplus complex than 12S rRNA or the
      nuclear marker ITS2. We suggest that future molecular studies of the R. microplus
      complex should focus on cox1, supplemented by 16S rRNA, and develop nuclear
      markers alternative to ITS2 to complement the mitochondrial data. 

PMID- 24685499
TI  - Integrating coalescent and phylogenetic approaches to delimit species in the
      lichen photobiont Trebouxia.
AB  - The accurate assessment of species boundaries in symbiotic systems is a
      prerequisite for the study of speciation, co-evolution and selectivity. Many
      studies have shown the high genetic diversity of green algae from the genus
      Trebouxia, the most common photobiont of lichen-forming fungi. However, the
      phylogenetic relationships, and the amount of cryptic diversity of these algae
      are still poorly understood, and an adequate species concept for trebouxiophycean
      algae is still missing. In this study we used a multifaceted approach based on
      coalescence (GMYC, STEM) and phylogenetic relationships to assess species
      boundaries in the trebouxioid photobionts of the lichen-forming fungus Lasallia
      pustulata. We further investigated whether putative species of Trebouxia found in
      L. pustulata are shared with other lichen-forming fungi. We found that L.
      pustulata is associated with at least five species of Trebouxia and most of them
      are shared with other lichen-forming fungi, showing different patterns of species
      to-species and species-to-community interactions. We also show that one of the
      putative Trebouxia species is found exclusively in association with L. pustulata
      and is restricted to thalli from localities with Mediterranean microclimate. We
      suggest that the species delimitation method presented in this study is a
      promising tool to address species boundaries within the heterogeneous genus
      Trebouxia. 

PMID- 24685500
TI  - Flavonoids and stilbenoids from Derris eriocarpa.
AB  - One new resveratrol analogue, 1-(3',4',5'-trimethoxyphenyl)-2-methoxy-2-(4"
      methoxyphenyl)-ethane-1-ol (1), and two new prenylisoflavones, 4'-hydroxy-5,7
      dimethoxy-6-(3-methyl-2-butenyl)-isoflavone (2), and derrubon 5-methyl ether (3),
      together with 17 known compounds including one new natural product, 5,7-dihydroxy
      3-[4'-O-(3-methyl-2-butenyl)-phenyl]-isoflavone (4), were isolated from the stems
      of ethnomedicinal plant Derris eriocarpa How. (Leguminosae). Their structures
      were elucidated based on chemical evidence and spectroscopic techniques including
      two-dimensional NMR methods. All compounds are reported from this species for the
      first time. Antimicrobial activities of the new compounds were evaluated.
      Compound 2 exhibited good inhibitory activities against Candida guilliermondii,
      C. albicans and Microsporium gypseum with the minimal inhibitory concentration
      (MIC) values of 12.5 MUg/ml.

PMID- 24685501
TI  - Two new diterpene derivatives from Euphorbia lunulata Bge and their anti
      proliferative activities.
AB  - A new ent-abietane-type diterpene lactone (1) and a new jatrophane-type
      diterpenoid (2), together with twelve known compounds including three diterpenes
      (3-5), five triterpenes (6-10) and four sterides (11-14) were isolated from the
      ethanol extract of the whole plant of Euphorbia lunulata Bge. The structure of
      compounds 1 and 2 was elucidated on the basis of 1D and 2D NMR spectra and the HR
      ESI-MS data. The structure of compound 2 was further analyzed by an X-ray
      crystallographic study. The in vitro anti-proliferative activities against MCF-7
      and NCI-H460 cell lines for compounds 1-5 (diterpene) were evaluated. The results
      showed marked activity for compound 1 against the two cell lines with the IC50
      values 19.5 (NCI-H460) and 18.6 (MCF-7) MUM, while for cis-platinum (a positive
      cytotoxic control agent) 29.7 (NCI-H460) and 27.7 (MCF-7) MUM. Compounds 2-5
      exhibited moderate cytotoxic activities for the two cell lines with the IC50
      values ranging from 32.1 to 58.2 MUM.

PMID- 24685502
TI  - New sesquiterpenic acids from Inula wissmanniana.
AB  - Eight new (1-8) and two known (9 and 10) sesquiterpenic acids featuring alpha
      methylene-gamma-carboxyl units were isolated from the whole plants of Inula
      wissmanniana, along with two new germacranolides (11 and 12). Their structures
      were elucidated based on detailed spectroscopic analysis, including HRESIMS, 1D
      and 2D NMR, and X-ray crystallography. Notably, the skeleton of 1 was firstly
      discovered from nature, while that of 2 was discovered for the second time. All
      the compounds were evaluated for their inhibition against LPS-induced nitric
      oxide (NO) production in RAW264.7 macrophages. Compound 11 exhibited the
      strongest activity with the IC50 value of 1.04 MUM.

PMID- 24685503
TI  - Polyacetylenes and anti-hepatitis B virus active constituents from Artemisia
      capillaris.
AB  - Three new polyacetylenes, 8-(Z)-decene-4, 6-diyne-1, 3, 10-triol (1), 1, 3S, 8S
      trihydroxydec-9-en-4, 6-yne (2), 3S, 8S-dihydroxydec-9-en-4, 6-yne 1-O-beta-D
      glucopyranoside (3), and one new glucosyl caffeoate, 1-O-ethyl-6-O-caffeoyl-beta
      D-glucopyranose (4), together with 34 known compounds were isolated from
      Artemisia capillaris. The structures of the new compounds were determined by
      extensive spectroscopic analyses including 1D and 2D NMR, HRESIMS, [alpha]D and
      CD experiments. Among them, 19 compounds showed activity inhibiting HBsAg
      secretion; 20 compounds showed activity inhibiting HBeAg secretion; and 25
      compounds possessed inhibitory activity against HBV DNA replication according to
      our anti-HBV assay on HepG 2.2.15 cell line in vitro. The most active compound 12
      could inhibit not only the secretions of HBsAg and HBeAg, but also HBV DNA
      replication with IC50 values of 15.02 MUM (SI=111.3), 9.00 MUM (SI=185.9) and
      12.01 MUM (SI=139.2).

PMID- 24685504
TI  - Indole alkaloids from the roots of Isatis indigotica and their inhibitory effects
      on nitric oxide production.
AB  - Three rare indole-2-S-glycosides, indole-3-acetonitrile-2-S-beta-D
      glucopyranoside (1), indole-3-acetonitrile-4-methoxy-2-S-beta-D-glucopyranoside
      (2) and N-methoxy-indole-3-acetonitrile-2-S-beta-D-glucopyranoside (3), together
      with 11 known indole alkaloids were isolated from the roots of Isatis indigotica
      Fort. (Cruciferae). The structures of 1-3 were elucidated on the basis of mass
      spectrometry and extensive 1D and 2D NMR spectroscopy. All of the isolated
      compounds were tested for inhibitory activity against LPS-induced nitric oxide
      production in RAW 264.7 macrophages. A plausible biosynthesis pathway of 1-3 is
      also proposed. 

PMID- 24685505
TI  - Anti-ulcer xanthones from the roots of Hypericum oblongifolium Wall.
AB  - Three new xanthones, hypericorin C (1), hypericorin D (2) and 3,4-dihydroxy-5
      methoxyxanthone (3), along with eight known compounds; 2,3-dimethoxyxanthone (4),
      3,4-dihydroxy-2-methoxyxanthone (5), 3,5-dihydroxy-1-methoxyxanthone (6), 3
      acetylbetulinic acid (7), 10H-1,3-dioxolo[4,5-b]xanthen-10-one (8), 3-hydroxy-2
      methoxyxanthone (9), 3,4,5-trihydroxyxanthone (10) and betulinic acid (11) were
      isolated from the roots of Hypericum oblongifolium. The structures of the new
      compounds 1, 2 and 3 were deduced by spectroscopic techniques [ESI MS, (1)H NMR,
      (13)C NMR, and 2D NMR (HMQC, HMBC, COSY and NOESY)]. The entire series of
      compounds were evaluated for anti-ulcer activity. 

PMID- 24685506
TI  - A C-methylated resacetophenone from Cistus monspeliensis L.
AB  - A new methylresacetophenone glucoside, named monspelioside, was isolated from
      Cistus monspeliensis, together with several diterpenes of labdane and clerodane
      types, a simple flavone and two methyl-inositols, one of them isolated for the
      first time from Cistus spp. 

PMID- 24685507
TI  - Two novel clerodane diterpenenes with NGF-potentiating activities from the twigs
      of Croton yanhuii.
AB  - Nerve growth factor (NGF) and analog reagents to promote the neurite outgrowth of
      nerve cells against the neuron degeneration are expected to be potentially useful
      for the medical treatment of Alzheimer's disease. In our focus on the discovery
      of bioactive diterpenes, we investigated the chemical constituents of the plant
      Croton yanhuii. This investigation led to the isolation and identification of two
      novel clerodane diterpenes (1 and 2). Their structures were elucidated on the
      basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESIMS
      and HR-ESIMS) spectroscopic data analyses. Further biological screenings showed
      that both of the compounds enhanced NGF-mediated neurite outgrowth from PC12
      cells. 

PMID- 24685508
TI  - Antiinflammatory activity of glucomoringin isothiocyanate in a mouse model of
      experimental autoimmune encephalomyelitis.
AB  - Glucomoringin (4(alpha-L-rhamnosyloxy)-benzyl glucosinolate) (GMG) is an uncommon
      member of glucosinolate group belonging to the Moringaceae family, of which
      Moringa oleifera Lam. is the most widely distributed. Bioactivation of GMG with
      the enzyme myrosinase forms the corresponding isothiocyanate (4(alpha-L
      rhamnosyloxy)-benzyl isothiocyanate) (GMG-ITC), which can play a key role in
      antitumoral activity and counteract the inflammatory response. The aim of this
      study was to assess the effect of GMG-ITC treatment in an experimental mouse
      model of multiple sclerosis (MS), an inflammatory demyelinating disease with
      neurodegeneration characterized by demyelinating plaques, neuronal, and axonal
      loss. For this reason, C57Bl/6 male mice were injected with myelin
      oligodendrocyte glycoprotein35-55 which is able to evoke an autoimmune response
      against myelin fibers miming human multiple sclerosis physiopatogenesis. Results
      clearly showed that the treatment was able to counteract the inflammatory cascade
      that underlies the processes leading to severe MS. In particular, GMG-ITC was
      effective against proinflammatory cytokine TNF-alpha. Oxidative species
      generation including the influence of iNOS, nitrotyrosine tissue expression and
      cell apoptotic death pathway was also evaluated resulting in a lower Bax/Bcl-2
      unbalance. Taken together, this work adds new interesting properties and
      applicability of GMG-ITC and this compound can be suggested as a useful drug for
      the treatment or prevention of MS, at least in association with current
      conventional therapy. 

PMID- 24685509
TI  - Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary
      perspective.
AB  - Nucleic acids derived from viral pathogens are typical pathogen associated
      molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by
      pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs)
      and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the
      release of inflammatory cytokines and type I interferons (IFNs) through the
      activation of nuclear factor kappaB (NF-kappaB) and interferon regulatory factor
      (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic
      acids can induce similar antiviral immunity in invertebrates remains ambiguous.
      Several studies have reported that nucleic acid mimics, especially dsRNA mimic
      poly(I:C), can strongly induce non-specific antiviral immune responses in
      insects, shrimp, and oyster. This behavior shows multiple similarities to the
      hallmarks of mammalian IFN responses. In this review, we highlight the current
      understanding of nucleic acid-induced antiviral immunity in invertebrates. We
      also discuss the potential recognition and regulatory mechanisms that confer non
      specific antiviral immunity on invertebrate hosts. 

PMID- 24685510
TI  - The immunomodulation of a novel tumor necrosis factor (CgTNF-1) in oyster
      Crassostrea gigas.
AB  - Tumor necrosis factor (TNF) is one of the most important cytokines involved in
      many processes in both vertebrate and invertebrate. In the present study, a new
      tumor necrosis factor with a typical TNF domain was identified in oyster
      Crassostrea gigas (designated CgTNF-1). CgTNF-1 shared low sequence identity and
      similarity with the TNF superfamily members from other vertebrate and
      invertebrate. After LPS stimulation, the mRNA expression of CgTNF-1 in haemocytes
      increased significantly and peaked at 12h (1.39+/-0.12, P<0.05) post treatment,
      and the expression of CgTNF-1 protein in haemolymph also increased obviously
      during 6-12h. When the oyster haemocytes were incubated with rCgTNF-1, its
      apoptosis and phagocytosis rate were both effectively induced and peaked at 12h
      post the treatment of rCgTNF-1 with the concentration of 100ngmL(-1) (23.3+/-3%,
      P<0.01), 50ngmL(-1) (5.3+/-0.6%, P<0.05) and 10ngmL(-1) (6.7+/-1.2%, P<0.05),
      respectively. After the co-stimulation of LPS and rCgTNF-1, the apoptosis and
      phagocytosis rate of oyster haemocytes, and the activities of PO and lysozyme in
      the haemolymph all increased significantly, and reached the peak at 12h
      (apoptosis rate 26.7+/-1.5%, P<0.01), 12h (phagocytosis rate 8.3+/-0.6%, P<0.01),
      6h (PO 1.11+/-0.01Umg prot(-1), P<0.01) and 12h (lysozyme 168.9+/-8.3Umg prot(
      1), P<0.05), respectively, which were significantly higher than that in the LPS
      group. Furthermore, the anti-bacteria activity in the LPS+TNF group was
      significantly higher than that in the LPS group during 6-12h. All the results
      collectively indicated that CgTNF-1 was involved in the oyster immunity and
      played a crucial role in the modulation of immune response including apoptosis
      and phagocytosis of haemocytes, and regulation of anti-bacterial activity as well
      as the activation of immune relevant enzymes. 

PMID- 24685512
TI  - Development of correction factors for landfill gas emission model suiting Indian
      condition to predict methane emission from landfills.
AB  - Methane emission from landfill gas emission (LandGEM) model was validated through
      the results of laboratory scale biochemical methane potential assay. Results
      showed that LandGEM model over estimates methane (CH4) emissions; and the true
      CH4 potential of waste depends on the level of segregation. Based on these
      findings, correction factors were developed to estimate CH4 emission using
      LandGEM model especially where the level of segregation is negligible or does not
      exist. The correction factors obtained from the study were 0.94, 0.13 and 0.74
      for food waste, mixed un-segregated municipal solid waste (MSW) and vegetable
      wastes, respectively. 

PMID- 24685513
TI  - Extracellular synthesis and characterization of nickel oxide nanoparticles from
      Microbacterium sp. MRS-1 towards bioremediation of nickel electroplating
      industrial effluent.
AB  - In the present study, a nickel resistant bacterium MRS-1 was isolated from nickel
      electroplating industrial effluent, capable of converting soluble NiSO4 into
      insoluble NiO nanoparticles and identified as Microbacterium sp. The formation of
      NiO nanoparticles in the form of pale green powder was observed on the bottom of
      the flask upon prolonged incubation of liquid nutrient medium containing high
      concentration of 2000ppm NiSO4. The properties of the produced NiO nanoparticles
      were characterized. NiO nanoparticles exhibited a maximum absorbance at 400nm.
      The NiO nanoparticles were 100-500nm in size with unique flower like structure.
      The elemental composition of the NiO nanoparticles was 44:39. The cells of MRS-1
      were utilized for the treatment of nickel electroplating industrial effluent and
      showed nickel removal efficiency of 95%. Application of Microbacterium sp. MRS-1
      would be a potential bacterium for bioremediation of nickel electroplating
      industrial waste water and simultaneous synthesis of NiO nanoparticles. 

PMID- 24685511
TI  - Perspectives on antigen presenting cells in zebrafish.
AB  - Antigen presentation is a critical step in the activation of naive T lymphocytes.
      In mammals, dendritic cells (DCs), macrophages, and B lymphocytes can all
      function as antigen presenting cells (APCs). Although APCs have been identified
      in zebrafish, it is unclear if they fulfill similar roles in the initiation of
      adaptive immunity. Here we review the characterization of zebrafish macrophages,
      DCs, and B cells and evidence of their function as true APCs. Finally, we discuss
      the conservation of APC activity in vertebrates and the use of zebrafish to
      provide a new perspective on the evolution of these functions. 

PMID- 24685514
TI  - Infantile anti-MuSK positive myasthenia gravis in a patient with autoimmune
      polyendocrinopathy type 3.
AB  - Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies and
      related to the muscle nicotinic acetylcholine receptor (AChR) or muscle-specific
      tyrosine kinase (MuSK). Myasthenia gravis with anti-MuSK antibodies rarely occurs
      in children. The present article reports a childhood onset case of auto-immune MG
      with anti-MuSK antibodies, part of autoimmune polyglandular syndrome. 

PMID- 24685515
TI  - Effect of hemodiafiltration or hemofiltration compared with hemodialysis on
      mortality and cardiovascular disease in chronic kidney failure: a systematic
      review and meta-analysis of randomized trials.
AB  - BACKGROUND: Whether convective modalities of dialysis, including hemofiltration
      (HF) and hemodiafiltration (HDF), improve cardiovascular outcomes and mortality
      is unclear. STUDY DESIGN: Systematic review and meta-analysis. SETTING &
      POPULATION: Patients receiving HDF, HF, or standard hemodialysis (HD). SELECTION
      CRITERIA FOR STUDIES: Randomized controlled trials. INTERVENTION: Convective
      modalities of dialysis (HDF and HF) versus standard HD. OUTCOMES: The primary
      outcome was clinical cardiovascular outcomes. Secondary outcomes were all-cause
      mortality, episodes of symptomatic hypotension, dialysis adequacy, and beta2
      microglobulin level. Relative risks (RRs) or weighted mean differences with 95%
      CIs for individual trials were pooled using random-effects models. RESULTS: The
      search yielded 16 trials including 3,220 patients. Therapies assessed were
      convective modalities (HDF or HF) compared with standard HD. Compared with HD,
      convective modalities did not significantly reduce the risk of cardiovascular
      events (RR, 0.85; 95% CI, 0.66-1.10) or all-cause mortality (RR, 0.83; 95% CI,
      0.65-1.05). Convective modalities reduced symptomatic hypotension (RR, 0.49; 95%
      CI, 0.30-0.81) and improved serum beta2-microglobulin levels (-5.95 mg/L; 95% CI,
      -10.27 to -1.64), but had no impact on small-molecule clearance (weighted mean
      difference in Kt/V, 0.04; 95% CI, -0.04 to 0.12). There was a nonsignificant
      trend to a greater likelihood of receiving a kidney transplant for participants
      allocated to filtration therapies (RR, 1.19; 95% CI, 0.99-1.42). LIMITATIONS: The
      trials were predominantly of suboptimal quality and underpowered, with imbalance
      in some prognostic variables at baseline. Intention-to-treat analysis was not
      used in some trials. Our analysis was limited to published outcomes. CONCLUSIONS:
      The potential benefits of convective modalities over standard HD for
      cardiovascular outcomes and mortality remain unproved. Further high-quality
      randomized trials are needed to define the impact of these modalities on
      clinically important outcomes.

PMID- 24685516
TI  - Neuroscientists do not use non-invasive brain stimulation on themselves for
      neural enhancement.

PMID- 24685517
TI  - Coarse-grained modeling of protein unspecifically bound to DNA.
AB  - There is now a certain consensus that transcription factors (TFs) reach their
      target sites, where they regulate gene transcription, via a mechanism dubbed
      facilitated diffusion (FD). In FD, the TF cycles between events of 3D diffusion
      in solution (jumps), 1D diffusion along DNA (sliding), and small jumps (hopping),
      achieving association rates higher than for 3D diffusion alone. We investigate
      the FD phenomenology through molecular dynamics simulations in the framework of
      coarse-grained modeling. We show that, despite the crude approximations, the
      model generates, upon varying the equilibrium distance of the DNA-TF interaction,
      a phenomenology matching a number of experimental and numerical results obtained
      with more refined models. In particular, focusing on the kinematics of the
      process, we characterize the geometrical properties of TF trajectories during
      sliding. We find that sliding occurs via helical paths around the DNA helix,
      leading to a coupling of translation along the DNA axis with rotation around it.
      The 1D diffusion constant measured in simulations is found to be interwoven with
      the geometrical properties of sliding and we develop a simple argument that can
      be used to quantitatively reproduce the measured values. 

PMID- 24685518
TI  - Effect of light on growth and endogenous hormones in Chlorella minutissima
      (Trebouxiophyceae).
AB  - Plant growth regulators (PGRs) play an important role in mediating growth and
      stress responses in plants. Light influences PGRs concentrations in vascular
      plants. The effect of light on growth and endogenous PGR concentrations in
      microalgae was investigated in the present study. Chlorella minutissima MACC 360
      was grown in 14:10 h light:dark (L:D), continuous dark (CD) and continuous dark
      with the addition of 5 g L(-1) glucose (CD + G) for 48 h. Cultures were
      synchronized in the L:D cultures, increasing in size during the light period and
      dividing during the dark period. C. minutissima cells did not increase in size or
      undergo cell division in CD cultures. In CD + G conditions, the cultures were no
      longer synchronized but did continue to increase in cell size and constantly
      underwent cell division although fewer cells divided than in the L:D cultures.
      Endogenous auxin and cytokinin concentrations increased and gibberellin
      concentrations decreased over time in the actively growing cultures (L:D and CD +
      G) but did not increase in the CD cultures. The largest increase in indole
      content was in the CD + G cultures while the L:D cultures had the largest
      cytokinin increase. Brassinosteroid concentrations decreased over time in all the
      cultures including those grown in CD conditions. Abscisic acid (ABA)
      concentrations were low and only increased in the CD cultures. These results show
      that endogenous PGRs were affected by the light regime and/or culture growth. 

PMID- 24685519
TI  - Protecting personal data in epidemiological research: DataSHIELD and UK law.
AB  - BACKGROUND: Data from individual collections, such as biobanks and cohort
      studies, are now being shared in order to create combined datasets which can be
      queried to ask complex scientific questions. But this sharing must be done with
      due regard for data protection principles. DataSHIELD is a new technology that
      queries nonaggregated, individual-level data in situ but returns query data in an
      anonymous format. This raises questions of the ability of DataSHIELD to
      adequately protect participant confidentiality. METHODS: An ethico-legal analysis
      was conducted that examined each step of the DataSHIELD process from the
      perspective of UK case law, regulations, and guidance. RESULTS: DataSHIELD
      reaches agreed UK standards of protection for the sharing of biomedical data. All
      direct processing of personal data is conducted within the protected environment
      of the contributing study; participating studies have scientific, ethics, and
      data access approvals in place prior to the analysis; studies are clear that
      their consents conform with this use of data, and participants are informed that
      anonymisation for further disclosure will take place. CONCLUSION: DataSHIELD can
      provide a flexible means of interrogating data while protecting the participants'
      confidentiality in accordance with applicable legislation and guidance.

PMID- 24685520
TI  - Transforming growth factor alpha promotes osteosarcoma metastasis by ICAM-1 and
      PI3K/Akt signaling pathway.
AB  - Osteosarcoma is the most common primary malignancy of bone and is characterized
      by a high malignant and metastatic potential. Transforming growth factor alpha
      (TGF-alpha) is classified as the EGF (epidermal growth factor)-like family, which
      is involved in cancer cellular activities such as proliferation, motility,
      migration, adhesion and invasion abilities. However, the effect of TGF-alpha on
      human osteosarcoma is largely unknown. We found that TGF-alpha increased the cell
      migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human
      osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced TGF-alpha
      mediated cell migration. We also found that the phosphatidylinositol 3'-kinase
      (PI3K)/Akt/NF-kappaB pathway was activated after TGF-alpha treatment, and TGF
      alpha-induced expression of ICAM-1 and cell migration was inhibited by the
      specific inhibitors and siRNAs of PI3K, Akt, and NF-kappaB cascades. In addition,
      knockdown of TGF-alpha expression markedly decreased cell metastasis in vitro and
      in vivo. Our results indicate that TGF-alpha/EGFR interaction elicits PI3K and
      Akt activation, which in turn activates NF-kappaB, resulting in the expression of
      ICAM-1 and contributing the migration of human osteosarcoma cells. 

PMID- 24685521
TI  - cDNA isolation and characterization of two vitellogenin genes in the Chagas'
      disease vector Triatoma infestans (Hemiptera, Reduviidae).
AB  - Two vitellogenin genes (Vg1 and Vg2) were identified in the Chagas' disease
      vector Triatoma infestans. The putative coding sequence corresponding to Vg2 was
      found to be 5553bp long, encoding 1851 amino acids in a single open reading
      frame. The comparative analysis of the deduced amino acid sequences from Vg1 and
      Vg2 cDNA fragments of T. infestans revealed 58.94% of identity with 76.43% of
      homology. The phylogenetic tree based on the complete Vg amino acid sequences of
      hemimetabolous insects unambiguously supported two clusters, one consisting of Vg
      sequences from dictyopteran and the other containing Vg sequences of hemipteran.
      The Vg1 and Vg2 mRNAs were detected in fat bodies and ovaries of adult females
      with the highest levels of both Vg transcripts in the first tissue. Quantitative
      PCR showed low expression of Vg2 in head and muscle of adult females, while the
      Vg1 transcript was not present in these organs. Neither Vg1 nor Vg2 was expressed
      in fifth instar nymph fat bodies or in adult male fat bodies, heads, and muscles.

PMID- 24685522
TI  - Prenatal skeletal dysplasia phenotype in severe MLII alpha/beta with novel GNPTAB
      mutation.
AB  - We report a neonate who was diagnosed as a case of skeletal dysplasia during
      pregnancy, and was subsequently diagnosed as a case of MLII alpha/beta on the
      basis of clinical and radiological findings and molecular testing of the parents.
      A novel GNPTAB mutation c.1701delC [p.F566LfsX5] was identified in the father.
      The case reiterates the severe prenatal phenotype of MLII alpha/beta which mimics
      skeletal dysplasia and illustrates the utility of molecular genetic analysis in
      confirmation of diagnosis and subsequent genetic counselling.

PMID- 24685524
TI  - MiR-291b-3p induces apoptosis in liver cell line NCTC1469 by reducing the level
      of RNA-binding protein HuR.
AB  - BACKGROUND: There is increasing evidence that miRNAs are involved in cellular
      apoptosis. However, the specific role of miR-291b-3p in apoptosis has not been
      elucidated. In the present study, we investigated the effect of miR-291b-3p on
      NCTC1469 cell growth and apoptosis. METHODS: Cell viability and apoptosis were
      examined in NCTC1469 cells transfected with miR-291b-3p mimics, inhibitor miRNA
      or negative control. Using computational miRNA target prediction databases, HuR
      was predicted as a target of miR-291b-3p. Luciferase assay, immunofluorescence
      and western blot were used to further explore the effects of miR-291b-3p on HuR
      expression. In addition, the effect of HuR on cell apoptosis was evaluated using
      a HuR-specific siRNA. RESULTS: TNF-alpha-induced hepatocyte apoptosis was
      accompanied by enhanced expression of miR-291b-3p, suggesting that miR-291b-3p
      might contribute to the apoptotic process. Follow-up experiments showed that
      upregulation of miR-291b-3p decreased cell viability and induced NCTC1469 cell
      apoptosis. Additionally, similar to the activity of miR-519, which is another
      member of the same miRNA family, miR-291b-3p suppressed HuR translation through
      binding to the HuR coding region (CR). We further showed that the downregulation
      of HuR expression by miR-291b-3p was accompanied by reduced Bcl-2 expression.
      Moreover, knockdown of HuR also impaired Bcl-2 expression and increased the ratio
      of Bax/Bcl-2. More significantly, downregulation of miR-291b-3p failed to
      increase Bcl2 expression in NCTC1469 cells that were co-transfected with siRNA
      HuR. Finally, inhibition of miR-291b-3p led to reduced apoptosis, while knockdown
      of HuR by siRNA promoted apoptosis, even in NCTC1469 cells that were co
      transfected with the miR-291b-3p inhibitor. CONCLUSION: The current data
      suggested that miR-291b-3p contributed to NCTC1469 cell apoptosis by regulating
      the expression of HuR, which in turn increased Bcl-2 stability.

PMID- 24685523
TI  - Control of an outbreak due to orthopedic infections caused by Enterobacteriaceae
      producing IMP-4 or IMP-8 carbapenemases.
AB  - OBJECTIVE: To investigate control of an outbreak due to orthopedic infections
      caused by Enterobacteriaceae producing IMP carbapenemases. METHODS: The sporadic
      orthopedic infections with Enterobacteriaceae producing carbapenemase (CPE) were
      retrospectively analyzed in a Chinese tertiary care hospital from November 2010
      to September 2012. RESULTS: The CPE were isolated from four distinct orthopedic
      patients, three patients infected with Enterobacter cloacae while the other with
      Klebsiella oxytoca. All strains were resistant to almost all the conventional
      antimicrobial. The strains produced IMP-4 type detected in the two early
      patients, while other strains could produce IMP-8 type. All of the four patients
      had ever undergoing invasive surgical procedure, and three of them were given
      fluoroquinolones for anti-infection treatment while the other patients was
      treated with meropenem. Ultimately, all patients were cured and discharged,
      without outbreak of nosocomial infection caused by CPE. CONCLUSION: Our study
      shows that strict infection control plays an important role in limiting
      dissemination of Enterobacteriaceae producing IMP carbapenemase. In addition,
      reasonable supporting treatment and disinfection protection seems to be more
      effective for the infection of strains.

PMID- 24685525
TI  - Whole joint MRI assessment of surgical cartilage repair of the knee: cartilage
      repair osteoarthritis knee score (CROAKS).
AB  - OBJECTIVE: To develop a magnetic resonance imaging (MRI) scoring system for
      follow-up of knee cartilage repair procedures integrating assessment of the
      repair site and the whole joint called Cartilage Repair OsteoArthritis Knee Score
      (CROAKS), and to assess its reliability. DESIGN: MRI examinations of 20 patients
      that had undergone matrix-associated autologous chondrocyte transplantation
      (MACT) of the knee 12 months before were semi-quantitatively assessed for the
      repair site using features of the magnetic resonance observation of cartilage
      repair tissue (MOCART) system and for the whole joint based on experiences with
      the MRI Osteoarthritis Knee Score (MOAKS) instrument. Intra- and inter-observer
      reliability was calculated using weighted (w) kappa statistics for plates
      (medial/lateral tibia, medial/lateral femur, trochlea, patella), compartments
      (medial tibio-femoral, lateral tibio-femoral, patello-femoral) and the whole
      joint. For certain features with low prevalence the overall percent agreement was
      calculated in addition. RESULTS: For cartilage, reliability on a plate level
      ranged between 0.48 (lateral femur) and 1.00 (medial femur). BML assessment
      showed comparable results ranging on a plate level between 0.46 and 1.00 with
      overall percent agreement between 83.3% and 100%. Meniscal morphology assessment
      ranged between 0.62 and 0.94. For repair site assessment reliability ranged from
      0.41 (signal intensity inter-observer) to 1.00 (several features). Overall
      percent agreement was above 80% for 17 of 22 features assessed (intra- and inter
      observer results combined). CONCLUSIONS: Combined scoring of the repair site and
      whole joint assessment for common osteoarthritis features using CROAKS, which is
      based on experience with two established semi-quantitative scoring tools, is
      feasible and may be performed with good to excellent reliability.

PMID- 24685526
TI  - Factors associated with arthrogenous muscle inhibition in patellofemoral
      osteoarthritis.
AB  - OBJECTIVES: Arthrogenous muscle inhibition (AMI) is thought to contribute to
      quadriceps weakness in knee osteoarthritis (OA), but its relationship with
      structural changes of bone marrow lesions (BMLs), capsular distension and pain is
      unclear. This study's objective was to investigate the factors associated with
      AMI in subjects with symptomatic patellofemoral joint OA (PFJOA). DESIGN: 126
      Subjects with predominant PFJOA were assessed for pain by the visual analogue
      scale (VAS) for a nominated aggravating activity. Their more symptomatic knee
      underwent a magnetic resonance imaging (MRI) scan which was used to assess BMLs
      and synovitis which were scored using the Whole Organ MRI score (WORMS).
      Quadriceps AMI was measured by calculating the activation deficit and quadriceps
      strength assessed by isometric maximum voluntary contraction. Multiple linear
      regressions were used to assess factors associated with AMI. RESULTS: We studied
      124 subjects [mean age 55.5 (SD 7.5); 57.14% female]. In regression analyses,
      higher levels of AMI were significantly associated with more severe knee pain and
      with lower BML score. CONCLUSION: Quadriceps AMI in knee OA is associated with
      severity of knee pain and surprisingly with lower BML scores.

PMID- 24685527
TI  - Screening of plant growth-promoting traits in arsenic-resistant bacteria isolated
      from agricultural soil and their potential implication for arsenic
      bioremediation.
AB  - Twelve arsenic (As)-resistant bacteria (minimum inhibitory concentration ranging
      from 10 to 30mM and 150 to 320mM for As(III) and As(V), respectively) were
      isolated from the agricultural soil of the Chianan Plain in southwestern Taiwan
      using enrichment techniques. Eight isolates capable of oxidizing As(III) (rate of
      oxidation from 0.029 to 0.059MUMh(-1) 10(-9) cell) and exhibiting As(III)-oxidase
      enzyme activity belong to Pseudomonas, Acinetobacter, Klebsiella and Comamonas
      genera, whereas four isolates that did not show As(III)-oxidizing activity belong
      to Geobacillus, Bacillus, Paenibacillus, and Enterobacter genera. Assessment of
      the parameters of plant growth promotion revealed that Pseudomonas sp. ASR1, ASR2
      and ASR3, Geobacillus sp. ASR4, Bacillus sp. ASR5, Paenibacillus sp. ASR6,
      Enterobacter sp. ASR10 and Comamonas sp. ASR11, and ASR12 possessed some or all
      of the studied plant growth-promoting traits, including phosphate-solubilization,
      siderophore, IAA-like molecules and ACC deaminase production. In addition, the
      ability of As-resistant isolates to grow over wide ranges of pH and temperatures
      signify their potential application for sustainable bioremediation of As in the
      environment. 

PMID- 24685528
TI  - A three-year experiment confirms continuous immobilization of cadmium and lead in
      contaminated paddy field with biochar amendment.
AB  - Heavy metal contamination in croplands has been a serious concern because of its
      high health risk through soil-food chain transfer. A field experiment was
      conducted in 2010-2012 in a contaminated rice paddy in southern China to
      determine if bioavailability of soil Cd and Pb could be reduced while grain yield
      was sustained over 3 years after a single soil amendment of wheat straw biochar.
      Contaminated biochar particles were separated from the biochar amended soil and
      microscopically analyzed to help determine where, and how, metals were
      immobilized with biochar. Biochar soil amendment (BSA) consistently and
      significantly increased soil pH, total organic carbon and decreased soil
      extractable Cd and Pb over the 3 year period. While rice plant tissues' Cd
      content was significantly reduced, depending on biochar application rate,
      reduction in plant Pb concentration was found only in root tissue. Analysis of
      the fresh and contaminated biochar particles indicated that Cd and Pb had
      probably been bonded with the mineral phases of Al, Fe and P on and around and
      inside the contaminated biochar particle. Immobilization of the Pb and Cd also
      occurred to cation exchange on the porous carbon structure. 

PMID- 24685529
TI  - Simultaneous removal of phenol, Cu and Cd from water with corn cob silica
      alginate beads.
AB  - Phenol and heavy metals in petroleum waste are environmental and human health
      concerns, but physicochemical removal is often cost-prohibitive and can produce
      toxic secondary products and treatment residues. An environmentally benign
      alternative combines corn cob silica with alginate and immobilized bacteria into
      beads for treating contaminated water. The concentration of phenol was decreased
      >92% by Pseudomonas putida YNS1 on aliginate-silica beads (2%, w/v) after
      equilibrating for 96h with water containing 214mg phenol/L. GC-MS analysis
      indicated formation of benzoquinone and other polar products. Beads containing
      corn cob silica decreased Cu concentrations by 84-88% and Cd by 83-87% within
      24h. In a mixture of 114mg phenol, 43mg Cu and 51mg Cd/L, phenol removal (93%
      within 96h) only occurred with beads containing the silica and bacterial strain.
      Beads containing corn cob silica removed >97% of the Cu and >99% of the Cd,
      critical for reducing toxicity to the bacteria. Beads with the immobilized strain
      removed phenol when zeolite was used instead of corn cob silica, but beads with
      silica were more effective for Cu and Cd removal. Results show the potential of
      corn cob silica combined with alginate and immobilized bacteria for removing
      phenol and heavy metals from contaminated water. 

PMID- 24685530
TI  - Photooxidation of cellulose nitrate: new insights into degradation mechanisms.
AB  - Cellulose nitrate (or nitrocellulose) has received considerable interest due to
      its uses in various applications, such as paints, photographic films and
      propellants. However, it is considered as one of the primary pollutants in the
      energetic material industries because it can be degraded to form polluting
      chemical species. In this work, the UV light degradation of cellulose nitrate
      films was studied under conditions of artificially accelerated photooxidation. To
      eliminate the reactivity of nitro groups, the degradation of ethylcellulose was
      also investigated. Infrared spectroscopy analyses of the chemical modifications
      caused by the photooxidation of cellulose nitrate films and the resulting
      formation of volatile products revealed the occurrence of de-nitration and the
      formation of oxidation photoproducts exhibiting lactone and anhydride functions.
      The impact of these chemical modifications on the mechanical and thermal
      properties of cellulose nitrate films includes embrittlement and lower
      temperatures of ignition when used as a propellant. 

PMID- 24685531
TI  - Cervical screening and cervical cancer death among older women: a population
      based, case-control study.
AB  - Recent research suggests that cervical screening of older women is associated
      with a considerable decrease in cervical cancer incidence. We sought to quantify
      the efficacy of cervical cytology screening to reduce death from this disease.
      Among enrollees of 2 US health plans, we compared Papanicolaou smear screening
      histories of women aged 55-79 years who died of cervical cancer during 1980-2010
      (cases) to those of women at risk of cervical cancer (controls). Controls were
      matched 2:1 to cases on health plan, age, and enrollment duration. Cytology
      screening during the detectable preclinical phase, estimated as the 5-7 years
      before diagnosis during which cervical neoplasia is asymptomatic but
      cytologically detectable, was ascertained from medical records. A total of 39
      cases and 80 controls were eligible. The odds ratio of cervical cancer death
      associated with screening during the presumed detectable preclinical phase was
      0.26 (95% confidence interval: 0.10, 0.63) after adjustment for matching
      characteristics, smoking, marital status, and race/ethnicity using logistic
      regression. We estimate that cervical cytology screening of all women aged 55-79
      years in the United States could avert 630 deaths annually. These results provide
      a minimum estimate of the efficacy of human papillomavirus DNA screening-a more
      sensitive test-to reduce cervical cancer death among older women. 

PMID- 24685533
TI  - Reproducibility of estradiol and testosterone levels in postmenopausal women over
      5 years: results from the breakthrough generations study.
AB  - Prospective cohort studies examining sex hormones in relation to cancer risk have
      generally collected blood samples at 1 time point, with an assumption that
      hormone levels measured in these samples will be reliable markers of true levels
      at other times. In postmenopausal women, body fat is a major source of estradiol;
      therefore, changes in adiposity may affect the correlation of single measurements
      to more relevant long-term averages. To estimate the intraclass correlation
      coefficient (ICC) for estradiol and testosterone, we collected repeat blood
      samples from 119 postmenopausal women (average age = 59.4 (standard deviation,
      4.7) years) from the United Kingdom during 2004-2005 and again during 2010-2011.
      The ICCs (adjusted for assay variation) were 0.73 (95% confidence interval: 0.63,
      0.82) for total estradiol and 0.59 (95% confidence interval: 0.47, 0.72) for
      total testosterone. The ICCs were 3%-5% larger after adjustment for change in
      body mass index (weight (kg)/height (m)(2)) or leptin, which are 2 markers of
      change in adiposity. There was no increase in ICCs after adjustment for change in
      age, alcohol consumption, smoking, exercise, time between waking and blood
      collection, or season. The results suggest that other factors account for within
      woman variation in these sex hormones. 

PMID- 24685532
TI  - Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year
      follow-up of a British population.
AB  - Epidemiologic studies have reported conflicting results on the relationship
      between daytime napping and mortality risk, and there are few data on the
      potential association in the British population. We investigated the associations
      between daytime napping and all-cause or cause-specific mortality in the European
      Prospective Investigation Into Cancer-Norfolk study, a British population-based
      cohort study. Among the 16,374 men and women who answered questions on napping
      habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up.
      Daytime napping was associated with an increased risk of all-cause mortality (for
      napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence
      interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard
      ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex,
      social class, educational level, marital status, employment status, body mass
      index, physical activity level, smoking status, alcohol intake, depression, self
      reported general health, use of hypnotic drugs or other medications, time spent
      in bed at night, and presence of preexisting health conditions. This association
      was more pronounced for death from respiratory diseases (for napping less than 1
      hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1
      hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in
      individuals 65 years of age or younger. Excessive daytime napping might be a
      useful marker of underlying health risk, particularly of respiratory problems,
      especially among those 65 years of age or younger. Further research is required
      to clarify the nature of the observed association. 

PMID- 24685534
TI  - Neuroprotective effects of hypothermia on synaptic actin cytoskeletal changes
      induced by perinatal asphyxia.
AB  - Cerebral hypoxia-ischemia damages synaptic proteins, resulting in cytoskeletal
      alterations, protein aggregation and neuronal death. In the previous works, we
      have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia
      that leads to ubi-protein accumulation. Recently, we also showed that, changes in
      F-actin organization could be related to early alterations induced by hypoxia in
      the Central Nervous System. However, little is known about effective treatment to
      diminish the damage. The main aim of this work is to study the effects of birth
      hypothermia on the actin cytoskeleton of neostriatal post-synaptic densities
      (PSD) in 60 days olds rats by immunohistochemistry, photooxidation and western
      blot. We used 2 different protocols of hypothermia: (a) intrahypoxic hypothermia
      at 15 degrees C and (b) post-hypoxia hypothermia at 32 degrees C. Consistent with
      previous data at 30 days, staining with phalloidin-Alexa(488) followed by
      confocal microscopy analysis showed an increase of F-actin fluorescent staining
      in the neostriatum of hypoxic animals. Correlative photooxidation electron
      microscopy confirmed these observations showing an increment in the number of
      mushroom-shaped F-actin staining spines in neostriatal excitatory synapses in
      rats subjected to hypoxia. In addition, western blot revealed beta-actin increase
      in PSDs in hypoxic animals. The optic relative density measurement showed a
      significant difference between controls and hypoxic animals. When hypoxia was
      induced under hypothermic conditions, the changes observed in actin cytoskeleton
      were blocked. Post-hypoxic hypothermia showed similar answer but actin
      cytoskeleton modifications were not totally reverted as we observed at 15 degrees
      C. These data suggest that the decrease of the body temperature decreases the
      actin modifications in dendritic spines preventing the neuronal death.

PMID- 24685535
TI  - Panic symptom profiles in social anxiety disorder: a person-centered data
      analytic approach.
AB  - Panic attacks (PAs) are prevalent among individuals with social anxiety disorder
      (SAD), but the clinical utility of panic symptom profiles is unclear. The aims of
      the present investigation were to empirically define panic symptom profiles in a
      treatment-seeking sample of individuals with SAD (N = 280) and to assess the
      associations of observed panic symptom profiles with clinical features of SAD.
      Results of a latent class analysis revealed four distinct panic symptom profiles:
      low panic symptoms, high typical SAD-related panic, high cardiac sensations and
      paresthesias, and moderate panic. Comparisons of external validators across
      latent classes indicated that the classes were differentially associated with
      clinical features of SAD. The present findings suggest that individuals with SAD
      experience distinct patterns of panic symptoms that may be clinically useful in
      conducting diagnostic assessments and determining treatment targets. 

PMID- 24685536
TI  - Alleviating distressing intrusive memories in depression: a comparison between
      computerised cognitive bias modification and cognitive behavioural education.
AB  - Negative appraisals maintain intrusive memories and intrusion-distress in
      depression, but treatment is underdeveloped. This study compared the efficacy of
      computerised bias modification positive appraisal training (CBM) versus a
      therapist-delivered cognitive behavioural therapy session (CB-Education) that
      both aimed to target and alter negative appraisals of a negative intrusive
      autobiographical memory. Dysphoric participants (Mean BDI-II = 27.85; N = 60)
      completed baseline ratings of a negative intrusive memory, negative appraisals
      and the Impact of Event Scale, and were randomly allocated either one session of
      CBM, CB-Education, or a no intervention monitoring control condition (Control).
      Mood and intrusion symptoms were assessed at one week follow-up. For all groups,
      there were significant reductions over one week in mood (depression and anxiety),
      memory intrusiveness and negative appraisals. Groups differed in terms of
      intrusion-related distress, with the CB-Education group showing greatest
      reduction, followed by the CBM group. The study provides evidence for the link
      between maladaptive appraisals of intrusive memories and distress in depressed
      mood. Further, both a single session of CB-Education and (to a lesser degree) CBM
      are useful in reducing intrusion-related distress. This study may have been
      underpowered to detect differences and replication is needed with larger samples.

PMID- 24685537
TI  - Multiplexing oscillatory biochemical signals.
AB  - In recent years it has been increasingly recognized that biochemical signals are
      not necessarily constant in time and that the temporal dynamics of a signal can
      be the information carrier. Moreover, it is now well established that the protein
      signaling network of living cells has a bow-tie structure and that components are
      often shared between different signaling pathways. Here we show by mathematical
      modeling that living cells can multiplex a constant and an oscillatory signal:
      they can transmit these two signals simultaneously through a common signaling
      pathway, and yet respond to them specifically and reliably. We find that
      information transmission is reduced not only by noise arising from the intrinsic
      stochasticity of biochemical reactions, but also by crosstalk between the
      different channels. Yet, under biologically relevant conditions more than 2 bits
      of information can be transmitted per channel, even when the two signals are
      transmitted simultaneously. These observations suggest that oscillatory signals
      are ideal for multiplexing signals. 

PMID- 24685538
TI  - Early prevention of childhood obesity: another promise or a reliable path for
      battling childhood obesity?

PMID- 24685539
TI  - The discovery and SAR of cyclopenta[b]furans as inhibitors of CCR2.
AB  - The discovery of a novel series of cyclopenta[b]furans as CCR2 inhibitors is
      discussed. This series has excellent CCR2 potency and PK characteristics, and
      good cardiovascular safety.

PMID- 24685540
TI  - Symmetric adamantyl-diureas as soluble epoxide hydrolase inhibitors.
AB  - A series of inhibitors of the soluble epoxide hydrolase (sEH) containing two urea
      groups has been developed. Inhibition potency of the described compounds ranges
      from 2.0 MUM to 0.4 nM. 1,6-(Hexamethylene)bis[(adamant-1-yl)urea] (3b) was found
      to be a potent slow tight binding inhibitor (IC50=0.5 nM) with a strong binding
      to sEH (Ki=3.1 nM) and a moderately long residence time on the enzyme (koff=1.05
      * 10(-3) s(-1); t1/2=11 min).

PMID- 24685541
TI  - Environmentally benign synthesis and antimicrobial study of novel
      chalcogenophosphates.
AB  - We report in this work an environmentally benign zinc mediated synthesis of aryl
      and benzyl phosphorochalcogenoates in ethanol within a short reaction time. In
      vitro antimicrobial study along with statistical analysis and seed germination
      assay were performed. These chalcogenophosphates possess strong antimicrobial
      activity against the reference strains. The antibacterial activity was determined
      against four standard strains (Bacilus subtilis, Staphylococcus aureus,
      Escherichia coli, Pseudomonas aeruginosa). The antifungal activity was evaluated
      against one fungal strain Candida albicans.

PMID- 24685543
TI  - Discovery of substituted benzamides as follicle stimulating hormone receptor
      allosteric modulators.
AB  - Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a
      pivotal role in the stimulation of follicular development and maturation.
      Multiple injections of protein formulations are used during clinical protocols
      for ovulation induction and for in vitro fertilization that are followed by a
      selection of assisted reproductive technologies. In order to increase patient
      convenience and compliance several research groups have searched for orally
      bioavailable FSH mimetics for innovative fertility medicines. We report here the
      discovery of a series of substituted benzamides as positive allosteric modulators
      (PAM) targeting FSHR. Optimization of this series has led to enhanced activity in
      primary rat granulosa cells, as well as remarkable selectivity against the
      closely related luteinizing hormone receptor (LHR) and thyroid stimulating
      hormone receptor (TSHR). Two modulators, 9j and 9k, showed promising in vitro and
      pharmacokinetic profiles.

PMID- 24685542
TI  - Purine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors for
      autoimmune diseases.
AB  - Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2
      yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors.
      Subsequent SAR studies of the purine series led to the discovery of 20 as a
      leading compound. Compound 20 is very selective when screened against a panel of
      400 kinases and is a potent inhibitor in cellular assays of human B cell function
      including B-Cell proliferation and CD86 cell surface expression and exhibited in
      vivo efficacy in a mouse PCA model. Its X-ray co-crystal structure with BTK shows
      that the high selectivity is gained from filling a BTK specific lipophilic
      pocket. However, physical and ADME properties leading to low oral exposure
      hindered further development.

PMID- 24685544
TI  - Identification of tertiary sulfonamides as RORc inverse agonists.
AB  - Screening a nuclear receptor compound subset in a RORc biochemical binding assay
      revealed a benzylic tertiary sulfonamide hit. Herein, we describe the
      identification of compounds with improved RORc biochemical inverse agonist
      activity and cellular potencies. These improved compounds also possessed
      appreciable selectivity for RORc over other nuclear receptors.

PMID- 24685545
TI  - Synthesis and cytotoxic activity of nitric oxide-releasing isosteviol
      derivatives.
AB  - Fifteen novel hybrids containing diterpene skeleton and nitric oxide (NO) donor
      were prepared from isosteviol. All the compounds were tested on preliminary
      cytotoxicity, and the results showed that six target compounds (8c, 10b, 14a,
      14c, 18c, and 18d) exhibited anti-proliferation activity on HepG2 cells, with 8c
      (IC50=4.24 MUM) and 18d (IC50=2.75 MUM) superior to the positive control CDDO-Me
      (2-cyano-3,12-dioxooleana-1,9(11)-dien-28-acid methyl ester, IC50=4.99 MUM);
      eleven target compounds (8a-c, 9a-c, 10a-b, 14a, 14c, 18d) exhibited anti
      proliferation activities on B16F10 cells at different levels, among them, seven
      compounds were more potent than comptothecin (IC50=2.78 MUM) and CDDO-Me
      (IC50=5.85 MUM), particularly, 10b (IC50=0.02 MUM) presented the strongest
      effect, which was selected as a candidate for further study.

PMID- 24685546
TI  - Successful application of serum shift prediction models to the design of dual
      targeting inhibitors of bacterial gyrase B and topoisomerase IV with improved in
      vivo efficacy.
AB  - A series of dual targeting inhibitors of bacterial gyrase B and topoisomerase IV
      were identified and optimized to mid-to-low nanomolar potency against a variety
      of bacteria. However, in spite of seemingly adequate exposure achieved upon IV
      administration, the in vivo efficacy of the early lead compounds was limited by
      high levels of binding to serum proteins. To overcome this limitation, targeted
      serum shift prediction models were generated for each subclass of interest and
      were applied to the design of prospective analogs. As a result, numerous
      compounds with comparable antibacterial potency and reduced protein binding were
      generated. These efforts culminated in the synthesis of compound 10, a potent
      inhibitor with low serum shift that demonstrated greatly improved in vivo
      efficacy in two distinct rat infection models.

PMID- 24685547
TI  - Ultrasound targeted apoptosis imaging in monitoring early tumor response of
      trastuzumab in a murine tumor xenograft model of her-2-positive breast
      cancer(1.).
AB  - OBJECTIVE: Our study aimed to monitor the trastuzumab therapy response of murine
      tumor xenograft model with human epidermal growth factor receptor 2 (Her-2)
      positive breast cancer using ultrasound targeted apoptosis imaging. METHODS: We
      prepared targeted apoptosis ultrasound probes by nanobubble (NB) binding with
      Annexin V. In vitro, we investigated the binding rate of NB-Annexin V with breast
      cancer apoptotic cells after the trastuzumab treatment. In vivo, tumor-bearing
      mice underwent ultrasound targeted imaging over 7 days. After imaging was
      completed, the tumors were excised to determine Her-2 and caspase-3 expression by
      immunohistochemistry (IHC). The correlation between parameters of imaging and
      histologic results was then analyzed. RESULTS: For seeking the ability of
      targeted NB binding with apoptotic tumor cells (Her-2 positive), we found that
      binding rate in the treatment group was higher than that of the control group in
      vitro (P = .001). There were no differences of tumor sizes in all groups over the
      treatment process in vivo (P = .98). However, when using ultrasound imaging to
      visualize tumors by targeted NB in vivo, we observed that the mean and peak
      intensities from NBs gradually increased in the treatment group after trastuzumab
      therapy (P = .001). Furthermore, these two parameters were significantly
      associated with caspase-3 expression of tumor excised samples (P = .0001).
      CONCLUSION: Ultrasound targeted apoptosis imaging can be a non-invasive technique
      to evaluate the early breast tumor response to trastuzumab therapy.

PMID- 24685548
TI  - Genome-wide polymorphisms and development of a microarray platform to detect
      genetic variations in Plasmodium yoelii.
AB  - The rodent malaria parasite Plasmodium yoelii is an important model for studying
      malaria immunity and pathogenesis. One approach for studying malaria disease
      phenotypes is genetic mapping, which requires typing a large number of genetic
      markers from multiple parasite strains and/or progeny from genetic crosses.
      Hundreds of microsatellite (MS) markers have been developed to genotype the P.
      yoelii genome; however, typing a large number of MS markers can be labor
      intensive, time consuming, and expensive. Thus, development of high-throughput
      genotyping tools such as DNA microarrays that enable rapid and accurate large
      scale genotyping of the malaria parasite will be highly desirable. In this study,
      we sequenced the genomes of two P. yoelii strains (33X and N67) and obtained a
      large number of single nucleotide polymorphisms (SNPs). Based on the SNPs
      obtained, we designed sets of oligonucleotide probes to develop a microarray that
      could interrogate ~11,000 SNPs across the 14 chromosomes of the parasite in a
      single hybridization. Results from hybridizations of DNA samples of five P.
      yoelii strains or cloned lines (17XNL, YM, 33X, N67 and N67C) and two progeny
      from a genetic cross (N67*17XNL) to the microarray showed that the array had a
      high call rate (~97%) and accuracy (99.9%) in calling SNPs, providing a simple
      and reliable tool for typing the P. yoelii genome. Our data show that the P.
      yoelii genome is highly polymorphic, although isogenic pairs of parasites were
      also detected. Additionally, our results indicate that the 33X parasite is a
      progeny of 17XNL (or YM) and an unknown parasite. The highly accurate and
      reliable microarray developed in this study will greatly facilitate our ability
      to study the genetic basis of important traits and the disease it causes. 

PMID- 24685550
TI  - Cardiac diseases complicating community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: The aim is to evaluate basic mechanisms, prevalence, risk
      factors, outcomes, and potential treatments of cardiovascular events (CVEs) in
      patients with community-acquired pneumonia (CAP). RECENT FINDINGS: In this
      review, we present a new model to evaluate the pathophysiology of cardiac disease
      in patients with pneumonia based on plaque-related events, such as acute
      myocardial infarction, versus plaque-unrelated events, such as arrhythmias and
      heart failure. CAP increases the risk for both plaque-related and plaque
      unrelated events with an absolute rate of CVE across different cohorts that
      varies broadly from 10 to 30%. These complications may happen among both
      ambulatory patients and inpatients, either on admission or during
      hospitalization, and/or after discharge. CVEs represent a major cause for
      increased mortality in CAP patients, contributing to more than 30% of deaths at
      long-term follow-up. SUMMARY: From a clinical perspective, especially during the
      first 24 h after hospitalization, CAP patients should be tested for the
      probability to have or develop during hospitalization a cardiac event. From a
      research point of view, there is an urgent need to prospectively evaluate
      cardioprotective interventions.

PMID- 24685549
TI  - Preparing for an era of untreatable gonorrhea.
AB  - PURPOSE OF REVIEW: The proportion of Neisseria gonorrhoeae isolates with reduced
      susceptibility to extended-spectrum cephalosporins (ESCs) has increased rapidly
      since 2006. Clinicians, researchers, and public health officials need to be
      prepared for the possibility of an era of untreatable gonorrhea. This review
      focuses on the evidence for current gonorrhea treatment recommendations,
      potential future treatment options, and other methods to control gonorrhea.
      RECENT FINDINGS: In addition to an increase in isolates with decreased
      susceptibility to ESCs, there have been reported treatment failures to both
      cefixime and ceftriaxone. In response, some countries have increased the
      recommended cephalosporin dose, and most now recommend dual therapy with an ESC
      and azithromycin. The pharynx has been implicated as a site for acquiring
      resistance through transformation with commensal Neisseria species or induced
      resistance through subtherapeutic antimicrobial levels. Thus, appropriate
      screening of the pharynx and treatment with a regimen that eradicates gonorrhea
      from the pharynx is necessary. At present, several studies are evaluating various
      novel treatment regimens in preparation for an era of untreatable gonorrhea.
      SUMMARY: Screening for asymptomatic infections, maintaining culture capacity to
      monitor antimicrobial resistance, treating with ceftriaxone and azithromycin, and
      ensuring that all sexual partners are treated are among the best strategies to
      control gonorrhea in the current clime.

PMID- 24685551
TI  - Skin manifestations of arthropod-borne infection in Latin America.
AB  - PURPOSE OF REVIEW: Arthropods are a significant cause of human skin lesions and
      infections, especially in Latin America. This review summarizes recent articles
      on the cutaneous manifestations of arthropod-borne diseases, with an emphasis on
      those diseases causing direct skin damage but also considering those systemic
      diseases with cutaneous manifestations. RECENT FINDINGS: Studies have shown a
      variety and increase of cutaneous manifestations caused by arthropod-borne
      infections, including petechiae, purpura, ulcers, nodules, atrophic, miliary and
      hyperpigmented lesions. Although unspecific, when considering other features they
      become a useful tool in the diagnostic approach. Unusual cutaneous presentation
      of these diseases has been found to be associated with development of immunity,
      virulent strain, drug resistance and immunosuppressive states. Also, because of
      globalization, climate change and large-scale migration, these manifestations
      have spread to new areas. SUMMARY: Cutaneous manifestations of arthropod-borne
      infections are varied and nonspecific. Their atypical presentations are mainly
      related to immune impairment and strain virulence. When considering a patient
      with skin lesions, other clinical and laboratory features must be taken into
      account in order to make an accurate diagnostic approach.

PMID- 24685552
TI  - Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired
      energy homeostasis and increased physical activity in mice.
AB  - Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation
      channels well characterized in neuronal signal transmission. Moreover, recent
      studies have revealed nAChR expression in nonneuronal cell types throughout the
      body, including tissues involved in metabolism. In the present study, we screen
      gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice
      pancreatic islets present predominant expression of alpha7 and beta2 nAChR
      subunits but at a lower level than in central structures. Characterization of
      glucose and energy homeostasis in alpha7beta2nAChR(-/-) mice revealed no major
      defect in insulin secretion and sensitivity but decreased glycemia apparently
      unrelated to gluconeogenesis or glycogenolysis. alpha7beta2nAChR(-/-) mice
      presented an increase in lean and bone body mass and a decrease in fat storage
      with normal body weight. These observations were associated with elevated
      spontaneous physical activity in alpha7beta2nAChR(-/-) mice, mainly due to
      elevation in fine vertical (rearing) activity while their horizontal (ambulatory)
      activity remained unchanged. In contrast to alpha7nAChR(-/-) mice presenting
      glucose intolerance and insulin resistance associated to excessive inflammation
      of adipose tissue, the present metabolic phenotyping of alpha7beta2nAChR(-/-)
      mice revealed a metabolic improvement possibly linked to the increase in
      spontaneous physical activity related to central beta2nAChR deficiency. 

PMID- 24685554
TI  - An in vitro study of the effect of probiotics, prebiotics and synbiotics on the
      elderly faecal microbiota.
AB  - The use of dietary intervention in the elderly in order to beneficially modulate
      their gut microbiota has not been extensively studied. The influence of two
      probiotics (Bifidobacterium longum and Lactobacillus fermentum) and two
      prebiotics [isomaltooligosaccharides (IMO) and short-chain fructooligosaccharides
      (FOS)], individually and in synbiotic combinations (B. longum with IMO, L.
      fermentum with FOS) on the gut microbiota of elderly individuals was investigated
      using faecal batch cultures and three-stage continuous culture systems.
      Population changes of major bacterial groups were enumerated using fluorescent in
      situ hybridisation (FISH). B. longum and IMO alone significantly increased the
      Bifidobacterium count after 5 and 10 h of fermentation and their synbiotic
      combination significantly decreased the Bacteroides count after 5 h of
      fermentation. L. fermentum and FOS alone significantly increased the
      Bifidobacterium count after 10 h and 5, 10 and 24 h of fermentation respectively.
      B. longum with IMO as well as B. longum and IMO alone significantly increased
      acetic acid concentration during the fermentation in batch cultures. In the three
      stage continuous culture systems, both synbiotic combinations increased the
      Bifidobacterium and Lactobacillus count in the third vessel representing the
      distal colon. In addition, the synbiotic combination of L. fermentum with scFOS
      resulted in a significant increase in the concentration of acetic acid. The
      results show that the elderly gut microbiota can be modulated in vitro with the
      appropriate pro-, pre- and synbiotics. 

PMID- 24685553
TI  - Complex changes in the liver mitochondrial proteome of short chain acyl-CoA
      dehydrogenase deficient mice.
AB  - Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive
      inborn error of metabolism that leads to the impaired mitochondrial fatty acid
      beta-oxidation of short chain fatty acids. It is heterogeneous in clinical
      presentation including asymptomatic in most patients identified by newborn
      screening. Multiple mutations have been identified in patients; however, neither
      clear genotype-phenotype relationships nor a good correlation between genotype
      and current biochemical markers for diagnosis has been identified. The definition
      and pathophysiology of this deficiency remain unclear. To better understand this
      disorder at a global level, quantitative alterations in the mitochondrial
      proteome in SCAD deficient mice were examined using a combined proteomics
      approach: two-dimensional gel difference electrophoresis (2DIGE) followed by
      protein identification with MALDI-TOF/TOF and iTRAQ labeling followed by nano
      LC/MALDI-TOF/TOF. We found broad mitochondrial dysfunction in SCAD deficiency.
      Changes in the levels of multiple energy metabolism related proteins were
      identified indicating that a more complex mechanism for development of symptoms
      may exist. Affected pathways converge on disorders with neurologic symptoms,
      suggesting that even asymptomatic individuals with SCAD deficiency may be at risk
      to develop more severe disease. Our results also identified a pattern associated
      with hepatotoxicity implicated in mitochondrial dysfunction, fatty acid
      metabolism, decrease of depolarization of mitochondria and mitochondrial
      membranes, and swelling of mitochondria, demonstrating that SCAD deficiency
      relates more directly to mitochondrial dysfunction and alteration of fatty acid
      metabolism. We propose several candidate molecules that may serve as markers for
      recognition of clinical risk associated with this disorder. 

PMID- 24685555
TI  - pH and bacterial profile of dental plaque in children and adults of a low caries
      population.
AB  - OBJECTIVE: This study compares pH and microbiological profile of dental plaque in
      children and adults of a low caries population. MATERIAL AND METHODS: Thirty-nine
      children, 12-14 years of age and 45 adults between 20 and 39 years of age in 5
      Karen villages of the Tak province, Northern Thailand were examined for plaque,
      calculus, caries (DMFT) and pH measurements in resting plaque and after a sucrose
      rinse. Information on dietary and oral hygiene habits was obtained through
      interviews using a fixed questionnaire. Microbiological profile of plaque samples
      was analyzed with DNA-DNA checkerboard technique. RESULTS: Mean DMFT was 0.77 +/-
      1.56 and 87% of the adults and 67% of the children were caries free (p < 0.05).
      The mean resting pH was for both age groups in the range of 7.0-7.1 and
      significantly higher than a Swedish caries free reference group. Karen adult men
      had significantly lower pH minimum than females and children (p < 0.05).
      Supragingival plaque samples showed high levels of low acidogenic and anaerobic
      species, which dominated over strong acid producers such as streptococci.
      CONCLUSION: The study indicates that the Karen children and adults has a plaque
      physiology and microbiology predominating by low acidogenic anaerobes, which in
      addition to the low sucrose intake explains the low caries prevalence in this
      population.

PMID- 24685556
TI  - Identification of pili on the surface of Finegoldia magna--a gram-positive
      anaerobic cocci.
AB  - Pili have only been discovered in the major Gram-positive pathogens in the past
      decade and they have been found to play an important role in colonisation and
      virulence. Pili have been shown to have many important functions including
      attachment to host tissues, mediating bacterial aggregation, biofilm formation
      and binding to proteins in the extracellular matrix. In this study, sortase
      dependent pili have been found to be expressed on the surface of Finegoldia magna
      ALB8. F. magna is a Gram-positive anaerobic coccus that, primarily, is a
      commensal of the skin and mucous membranes, but has also been isolated from
      various clinical infection sites and is associated with soft-tissue abscesses,
      wound infections and bone and prosthetic joint infections. In this study, F.
      magna ALB8 was found to harbour three sortases at the pilus locus, two of which
      bear high similarity to class C sortases in Streptococcus pneumoniae. Two
      putative sortase-dependent pili proteins were found in the locus, with one being
      identified as the major pilus subunit, Fmp1 (F. magna pilus subunit 1), due to
      its high similarity to other major pilus proteins in prominent Gram-positive
      pathogens. The presence of sortase-dependent pili was confirmed experimentally
      through recombinant production of Fmp1 and production of antiserum. The Fmp1
      antiserum was used in Western blot to show the presence of a high molecular
      weight protein ladder, characteristic of the presence of pili, in trypsin
      released cell wall surface proteins from F. magna. The presence of sortase
      dependent pili was visually confirmed by transmission electron microscopy, which
      showed the binding of gold labelled anti-Fmp1 to individual pilus proteins along
      the pilus. Furthermore, pili could also be found to bind and interact with
      keratinocytes in the epidermal layer of human skin, suggesting an adhesive role
      for pili on F. magna. Our work represents the first description of pilus
      structures in F. magna. This discovery further elucidates F. magna physiology and
      allows for additional analysis of host-bacterial interactions in future studies. 

PMID- 24685557
TI  - Discordance between self-report and genetic confirmation of sickle cell disease
      status in African-American adults.
AB  - BACKGROUND: Sickle cell disease (SCD) is an autosomal recessive genetic disorder,
      with persons heterozygous for the mutation said to have the sickle cell trait
      (SCT). Serious adverse effects are mainly limited to those with SCD, but the
      distinction between disease and trait is not always clear to the general
      population. We sought to determine the accuracy of self-reported SCD when
      compared to genetic confirmation. METHODS: From stratified random samples of
      Southern Community Cohort Study participants, we sequenced the beta- globin gene
      in 51 individuals reporting SCD and 75 individuals reporting no SCD. RESULTS: The
      median age of the group selected was 53 years (range 40-69) with 29% male. Only
      5.9% of the 51 individuals reporting SCD were confirmed by sequencing, with the
      remaining 62.7% having SCT, 5.9% having hemoglobin C trait, and 25.5% having
      neither SCD nor trait. Sequencing results of the 75 individuals reporting no SCD
      by contrast were 100% concordant with self-report. CONCLUSIONS: Misreporting of
      SCD is common in an older adult population, with most persons reporting SCD in
      this study being carriers of the trait and a sizeable minority completely
      unaffected. The results from this pilot survey support the need for increased
      efforts to raise community awareness and knowledge of SCD.

PMID- 24685558
TI  - Palmitate induces TRB3 expression and promotes apoptosis in human liver cells.
AB  - BACKGROUND/AIMS: Parenteral nutrition-associated liver disease (PNALD) is a major
      complication for patients who require long-term parenteral nutrition. Treatment
      options for PNALD are limited and its pathogenesis is poorly understood. Tribbles
      homolog 3 (TRB3) is a pseudokinase that modulates many signal transduction
      cascades and may be involved in the pathogenesis of PNALD. The aim of this study
      was to examine the role of TRB3 in palmitate-induced endoplasmic reticulum (ER)
      stress, in the human liver cell line L02. METHODS: L02 cells were treated with
      palmitate, and its effect on cell viability, mitochondrial membrane potential,
      apoptosis and TRB3 expression were assessed. The role of TRB3 was also studied
      using transient overexpression of TRB3 in L02 cells, as well as its interaction
      with Akt signaling. RESULTS: We found that palmitate induced ER stress and
      apoptosis in L02 cells. Palmitate-associated ER stress was accompanied by a
      significant induction of TRB3 expression at the mRNA and protein level.
      Overexpression of TRB3 potentiated the deleterious effects of palmitate, which
      was associated with decreased levels of phospho-Akt. CONCLUSIONS: TRB3 is an
      important mediator of palmitate-induced apoptosis in human liver cells,
      suggesting that it may also be involved in the molecular mechanism underlying
      PNALD.

PMID- 24685560
TI  - Poly-tobacco use among adults in 44 countries during 2008-2012: evidence for an
      integrative and comprehensive approach in tobacco control.
AB  - INTRODUCTION: The concurrent use of multiple tobacco products (i.e., poly-tobacco
      use) might hinder efforts to reduce overall tobacco use, particularly considering
      that use of some non-cigarette tobacco products may be popular in some regions
      due to social, cultural, or economic reasons. This study assessed poly-tobacco
      use patterns among persons aged >=15 years old from 44 countries. METHODS: Data
      from 44 countries in all six World Health Organization regions were obtained from
      the 2008 to 2012 Global Adult Tobacco Surveys (n=19 countries), and the Special
      Eurobarometer 385 (77.1) survey, 2012 (n=25 countries). Correlates of poly
      tobacco use were assessed using multivariate logistic regression analyses
      (p<0.05). RESULTS: Overall prevalence of poly-tobacco use ranged from 0.8%
      (Mexico) to 11.9% (Denmark). In 28 countries, 20% or more of current smokers of
      manufactured cigarettes concurrently used at least one other tobacco product and
      this proportion was highest in India (66.2%) and lowest in Argentina (4.4%).
      After adjusting for other factors, the likelihood of being a poly-tobacco user
      among all respondents was lower among females (aOR=0.09; 95% CI: 0.08-0.11), and
      among respondents from upper-middle-income (aOR=0.53, 95% CI: 0.43-0.66), and
      lower-middle-income countries (aOR=0.64; 95% CI: 0.51-0.81) compared to high
      income countries. Increased likelihood of poly-tobacco use was observed among
      respondents from the South-East Asian region compared to those from the European
      region (aOR=1.58, 95% CI: 1.35-1.85), as well as among respondents aged >=65
      years (aOR=2.10; 95% CI: 1.73-2.54), compared to those aged <25 years.
      CONCLUSIONS: The pattern of tobacco use varied widely, underscoring the need for
      intensified efforts towards implementing policies that address all tobacco
      products, not only manufactured cigarettes.

PMID- 24685559
TI  - Changing motives for use: outcomes from a cognitive-behavioral intervention for
      marijuana-dependent adults.
AB  - BACKGROUND: Motives for use have been identified as important predictors of
      substance use and related problems; however, little is known about how motives
      for use change following an intervention and how this change may impact future
      substance use behaviors. The present study sought to describe change in motives
      following an intervention for marijuana-dependent adults. Furthermore,
      investigators examined change in motives as a predictor of treatment outcome.
      METHOD: The study randomized 74 adults to one of two conditions: both of which
      received 9-sessions base treatment of cognitive behavioral therapy and
      motivational enhancement therapy and had access to additional sessions of
      cognitive behavioral treatment on an as-needed basis. The experimental condition
      received two additional "check-ups" during the course of follow-up. RESULTS:
      Significant decreases in reported frequency of motives used were observed
      following treatment. Changes in Expansion and Coping were associated with
      differential treatment outcomes. Decreases in Expansion were associated with
      poorer treatment outcome, while decreases in Coping were associated with better
      treatment outcome. CONCLUSIONS: The relationship between expansion motives and
      outcomes was paradoxical. Although there were some inconsistencies in the
      findings, the results regarding the coping motive were consistent with hypotheses
      and may have important implications for treatment.

PMID- 24685561
TI  - Effect of experimental analogs of contingency management treatment on cocaine
      seeking behavior.
AB  - BACKGROUND: Contingency management (CM) treatment is effective for treating
      cocaine dependence but further mechanistic studies of its efficacy are warranted.
      This study aimed to determine whether: (a) higher vs. lower predictable money
      amounts ($3 vs. $1; analogs of standard voucher-based CM) increase cocaine demand
      elasticity; and (b) probabilistic amounts matched for expected value with the $3
      predictable amount (50% chance of $6; 25% chance of $12; and 12.5% chance of $24;
      analogs of prize CM) similarly affect cocaine choice. METHODS: Each of 15 cocaine
      dependent participants first completed a qualifying session to ensure that
      intranasal cocaine functioned as a reinforcer, then completed a 10-session,
      within-subject, randomized crossover study. During each of the 10 sessions, the
      participant responded on a progressive ratio schedule to earn units of cocaine (5
      mg or 10-mg) and/or money (five monetary conditions above). RESULTS: During the
      reinforcement qualifying session (10-mg vs. 0-mg units; no money alternative),
      cocaine choice was high. The $3-predictable amount significantly decreased
      cocaine choice relative to both the $1-predictable amount and the qualifying
      session. Cocaine-choices in the probabilistic conditions were similar to the $3
      predictable condition. CONCLUSIONS: These findings indicate that CM interventions
      targeted at reducing cocaine self-administration are more likely to succeed with
      higher value non-drug reinforcement.

PMID- 24685562
TI  - Changes in alcohol use after traumatic experiences: the impact of combat on Army
      National Guardsmen.
AB  - OBJECTIVE: This research documents the impact of combat experiences on alcohol
      use and misuse among National Guard soldiers. Whereas much research regarding
      combat personnel is based on post-experience data, this study's design uses both
      pre- and post-deployment data to identify the association between different types
      of combat experiences and changes in substance use and misuse. METHOD: A National
      Guard Infantry Brigade Combat Team was surveyed before and after its deployment
      to Iraq in 2005-2006. Members of the unit completed anonymous surveys regarding
      behavioral health and alcohol use and, in the post-survey, the combat experiences
      they had during deployment. The unit was surveyed 3 months prior to its
      deployment and 3 months after its deployment. RESULTS: Prevalence rates of
      alcohol use increased from 70.8% pre-deployment to 80.5% post-deployment.
      Prevalence rates of alcohol misuse more than doubled, increasing from 8.51%
      before deployment to 19.15% after deployment. However, among the combat
      experiences examined in this study, changes in alcohol misuse post-deployment
      appear to be solely affected by the combat experience of killing. Alcohol misuse
      decreased amongst those who experienced killing during combat. CONCLUSIONS: This
      study highlights the role of combat experiences on substance use.

PMID- 24685563
TI  - Time to relapse following treatment for methamphetamine use: a long-term
      perspective on patterns and predictors.
AB  - INTRODUCTION: This paper describes methamphetamine (MA) use patterns,
      specifically the duration of continuing abstinence ("time to relapse") for
      periods averaging 5 years post-discharge from treatment for MA use, and the
      relationship with selected user and treatment characteristics. METHODS: A sample
      of 350 treatment admissions from a large county substance use disorder (SUD)
      treatment system was randomly selected (within gender, race/ethnicity, treatment
      modality strata). Retrospective self-report data are from natural history
      interviews (NHI) conducted approximately 3 years after treatment and a follow-up
      of 2-3 years later. Relapse is defined as any use of MA with time as the number
      of months of continuous MA abstinence after treatment discharge until relapse.
      This outcome was constructed from a monthly MA use timeline using NHI data. A Cox
      model was used to examine time to relapse and predictors. RESULTS: Sixty-one
      percent of the sample relapsed to MA use within 1 year after treatment discharge
      and 14% during years 2-5. Significant protective factors predicting longer time
      to relapse included having experienced serious MA-related psychiatric/behavioral
      problems (hazard ratio [HR]=0.75, p=0.027), longer duration of the index
      treatment episode (HR=0.93, p=0.001), and participating in self-help or other
      treatment during the post-treatment abstinence period (HR=0.29, p<0.001); risk
      factors for shorter time to relapse included having a parent with alcohol and/or
      drug use problems (HR=1.35, p=0.020) and involvement in MA sales (HR=1.48,
      p=0.002). CONCLUSIONS: Results contribute a long-term perspective on patterns of
      MA use following treatment and support a need for early post-treatment and long
      term continuing care and relapse-prevention services.

PMID- 24685564
TI  - Chronic morphine treatment induces over-expression of HSP70 in mice striatum
      related with abnormal ubiquitin-proteasome degradation.
AB  - BACKGROUND: It has been shown that opioid dependence-related neuronal plasticity
      may rely not only on protein synthesis, but also on protein degradation, mainly
      mediated by ubiquitin-proteasome system (UPS). The aim of the present study was
      to determine the effect of morphine on the regulation of protein degradation in
      the brain and to determine which proteins are involved in the underlying
      mechanism. METHODS: Mice were given chronic morphine administration and the state
      of morphine dependence was confirmed by induction of naloxone-precipitated
      withdrawal jumping. The level of ubiquitinated proteins in the striatum and
      spinal cord of morphine-dependent mice was detected by Western blotting. One of
      the abnormal-ubiquitinated proteins in mice striatum was identified by
      electrospray ionization quadrupole time-of-flight tandem mass spectrometry and
      the result was further confirmed by Western blotting and immunofluorescence
      method. RESULTS: We found that the expression of some ubiquitinated proteins was
      clearly decreased in the striatum of morphine-depnendent mice, but not in the
      spinal cord. And we identified a ubiquitinated protein (>79 kDa) decreased in the
      striatum as heat shock cognate 70 protein, one member of the 70 kDa family of
      heat shock proteins (HSP70). Moreover, we confirmed the level of HSP70 protein
      was significantly increased in mice striatum. CONCLUSIONS: These data strongly
      suggest morphine-induced HSP70 overexpression in the striatum is closely related
      with its abnormal degradation by UPS and it seems to be an important mechanism
      associated with morphine dependence.

PMID- 24685566
TI  - A novel protein extracted from foxtail millet bran displays anti-carcinogenic
      effects in human colon cancer cells.
AB  - Millet is an important cereal food and exhibits multiple biological activities,
      including immunodulatory, antioxidant, antifungal and anti-hyperglycemia effects.
      Herein, we describe a novel 35kDa protein with anti-cancer properties, named
      FMBP, which was extracted and purified from foxtail millet bran by cell-based
      screening. FMBP is highly homologous to peroxidase as revealed by mass
      spectrometry and gene sequencing analysis. Furthermore, in vivo anti-tumor
      results implicated that the novel protein FMBP had the ability to suppress
      xenografted tumor growth in nude mice. Mechanistically, FMBP is able to suppress
      colon cancer cell growth through induction of G1 phase arrest and also causes a
      loss of mitochondrial transmembrane potential which results in caspase-dependent
      apoptosis in colon cancer cells. Notably, FMBP has much lower toxicity in normal
      colon epithelial cells. Taken together, FMBP has targeted anti-colon cancer
      effects and may serve as a therapeutic agent against colon cancer. 

PMID- 24685567
TI  - Editorial comment.

PMID- 24685565
TI  - Novel molecular aspects of ghrelin and leptin in the control of adipobiology and
      the cardiovascular system.
AB  - Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a
      gut hormone that is secreted to the bloodstream in two major forms, acylated and
      desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the
      activation of hypothalamic orexigenic neurons but also directly stimulate the
      expression of several fat storage-related proteins in adipocytes, including ACC,
      FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation.
      Moreover, both acylated and desacyl ghrelin reduce TNF-alpha-induced apoptosis
      and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in
      human adipose tissue. On the other hand, leptin is an adipokine with lipolytic
      effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of
      aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from
      adipocytes in response to the lipolytic stimuli via its translocation from the
      cytosolic fraction (AQP3) or lipid droplets (AQP7) to the plasma membrane.
      Ghrelin and leptin also participate in the homeostasis of the cardiovascular
      system. Ghrelin operates as a cardioprotective factor with increased circulating
      acylated ghrelin concentrations in patients with left ventricular hypertrophy
      (LVH) causally related to LV remodeling during the progression to LVH.
      Additionally, leptin induces vasodilation by inducible NO synthase expression
      (iNOS) in the vascular wall. In this sense, leptin inhibits the angiotensin II
      induced Ca(2+) increase, contraction and proliferation of VSMC through NO
      dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and
      leptin resistance associated to obesity, type 2 diabetes, or the metabolic
      syndrome contribute to cardiometabolic derangements observed in these
      pathologies.

PMID- 24685568
TI  - Affective and cognitive reactions to subliminal flicker from fluorescent
      lighting.
AB  - This study renews the classical concept of subliminal perception (Peirce &
      Jastrow, 1884) by investigating the impact of subliminal flicker from fluorescent
      lighting on affect and cognitive performance. It was predicted that low compared
      to high frequency lighting (latter compared to former emits non-flickering light)
      would evoke larger changes in affective states and also impair cognitive
      performance. Subjects reported high rather than low frequency lighting to be more
      pleasant, which, in turn, enhanced their problem solving performance. This
      suggests that sensory processing can take place outside of conscious awareness
      resulting in conscious emotional consequences; indicating a role of affect in
      subliminal/implicit perception, and that positive affect may facilitate cognitive
      task performance. 

PMID- 24685569
TI  - Outcomes following the conservative management of patients with non-radicular
      peripheral neuropathic pain.
AB  - STUDY DESIGN: Prospective cohort. INTRODUCTION: There is limited evidence for
      conservative management of patients with non-radicular peripheral neuropathic
      pain (PNP). PURPOSE: To investigate the effectiveness of a comprehensive
      treatment approach on pain and disability in patients with non-radicular PNP and
      to determine if improvements are maintained following the discontinuation of
      therapy. METHODS: Patients received a multi-modal therapeutic intervention.
      Outcome measures were the shortened version of the Disabilities of the Arm,
      Shoulder and Hand questionnaire (QDASH), Numeric Pain Rating Scale (NPRS), and
      grip strength. Follow-up data were collected 5 +/- 2 months post-discharge.
      RESULTS: There was a significant improvement in the QDASH and mean pain (p <
      .001). There was no significant change in grip strength (p > .13). Follow-up data
      suggest that pain and disability scores are maintained (p < .001). CONCLUSION: A
      comprehensive, conservative treatment program has a positive and lasting effect
      on pain and disability scores in patients with non-radicular PNP. LEVEL OF
      EVIDENCE: IIIa.

PMID- 24685570
TI  - GNE myopathy: new name and new mutation nomenclature.

PMID- 24685571
TI  - Detection of anti-periplakin auto-antibodies during idiopathic pulmonary
      fibrosis.

PMID- 24685572
TI  - Comparison of KRAS mutation analysis of primary tumors and matched circulating
      cell-free DNA in plasmas of patients with colorectal cancer.
AB  - Colorectal cancer (CRC) patients with KRAS mutations do not benefit from
      epidermal growth factor receptor (EGFR) targeted therapy. In clinical practice,
      identifying patients with KRAS mutations is critical prior to EGFR targeting
      therapy, and gene testing is generally performed using the DNA extracted from
      tumor tissue. The aim of this study was to compare the presence of KRAS mutations
      in circulating cell-free DNA (cfDNA) and primary tumor tissue using a peptide
      nucleic acid mediated polymerase chain reaction. We extracted and analyzed the
      DNA from plasmas and corresponding primary tumor samples from 52 patients with
      CRC. The results demonstrated that the detection rate of KRAS sequence variations
      was 50% (26 of 52) in plasma samples and 28.8% (15 of 52) in resected primary
      tumor tissue samples. The majority of KRAS mutations detected in tumors were also
      found in matched plasma specimens with an agreement rate of 78.8%. Eleven plasma
      cfDNA were found positive for KRAS mutation but not in their corresponding
      tissue. In conclusion, our results suggest that circulating cfDNA provides a
      better representation of the malignant disease as a whole and could be a reliable
      source of diagnostic DNA to replace the tumor tissue in a diagnostic setting. 

PMID- 24685573
TI  - A prospective tool for risk assessment of sendout testing.
AB  - OBJECTIVE: Errors associated with laboratory testing can cause significant
      patient harm. Sendout testing refers to tests sent by a primary lab to a
      reference lab when testing is unavailable at the primary lab. Sendout testing is
      particularly high risk for patient harm, due to many factors including increased
      hand-offs, manual processes, and complexity associated with rare, low-volume
      tests. No published prospective tools exist for sendout risk assessment. METHODS:
      A novel prospective tool was developed to assess risk of diagnostic errors
      involving laboratory sendout testing. This tool was successfully piloted at nine
      sites. RESULTS: Marked diversity was noted among survey respondents, particularly
      in the sections on quality metrics and utilization management. Of note, most
      sites had committees who managed rules for test ordering, but few places reported
      enforcing these rules. Only one site claimed to routinely measure the frequency
      clinicians failed to retrieve test results. An evaluation of the tool indicated
      that it was both useful and easy to use. CONCLUSIONS: This tool could be used by
      other laboratories to identify the areas of highest risk to patients, which in
      turn may guide them in focusing their quality improvement efforts and resources.

PMID- 24685574
TI  - Should all screen-positive elevated blood lead (EBL) samples be retested before
      reporting?

PMID- 24685575
TI  - Author's reply to "detection of anti-periplakin autoantibodies during idiopathic
      pulmonary fibrosis" by Taille et al.

PMID- 24685576
TI  - Structural investigation and immunological activity of a heteropolysaccharide
      from Sargassum fusiforme.
AB  - A heteropolysaccharide was isolated from the brown alga, Sargassum fusiforme. The
      heteropolysaccharide was estimated to have a molecular weight of 11kDa and showed
      [alpha]D(20) -62.2420 (c 0.05, H2O). SFPS65-B comprised galactose, glucose,
      mannose, fucose, and galacturonic acid at a ratio of 3.04:1:1.15:2.82:6.51. Its
      structural features were investigated using composition analysis, methylation
      analysis, IR, NMR spectroscopy, and ESI-Q-TOF MS spectroscopy. Results showed
      that SFPS65-B contained the backbone of ->4)-alpha-GalAp-(1->4)-alpha-Hexp-(1->4)
      alpha-GalAp-(1->4)-alpha-Fucp-(1->4)-alpha-GalAp-(1->. The sulfated unit and
      terminal fucose residues were attached onto the backbone through the O-2 of some
      galactose residues. Results also showed that SFPS65-B had a good effect on thymus
      and spleen indices at a dose of 100mg/kg upon immunosuppression in
      cyclophosphamide-treated mice. 

PMID- 24685577
TI  - Strange bedfellows: mitotically active chronic myeloid leukemia in molecular
      complete remission, detected in focal lesion of myeloma.

PMID- 24685578
TI  - T cell-depleted related HLA-mismatched peripheral blood stem cell transplantation
      as salvage therapy for graft failure after single unit unrelated donor umbilical
      cord blood transplantation.
AB  - Graft failure is a severe treatment complication of unrelated donor umbilical
      cord blood transplantation (UCBT). Its incidence seems to be higher after UCBT
      than after transplantation with bone marrow or peripheral blood stem cells
      (PBSCs). The only curative option is to perform a second transplantation;
      however, both the ideal stem cell source and the conditioning regimen for this
      salvage transplantation remain unclear. We report a series of 11 patients who
      underwent haploidentical PBSC transplantation (PBSCT) as salvage therapy for
      graft failure after a previous UCBT. The reduced-intensity conditioning regimen
      consisted of fludarabine 150 mg/m(2) for 3 days and horse antithymocyte globulin
      8 mg/kg for 4 days. Ex vivo CD34(+) positive selection was performed in all
      cases, and no post-transplantation graft-versus-host disease prophylaxis was
      used. Six of the 9 evaluable patients (67%) eventually engrafted, at a median
      time of 10 days. The cumulative incidence of engraftment at 28 days was 64% (95%
      confidence interval [CI], 35% to 92%). Two patients relapsed after PBSCT. The
      cumulative incidence of TRM was 55% at 2 years (95% CI, 25% to 84%), and the
      probability of overall survival at 2 years was 36%. Our findings suggest that
      haploidentical ex vivo T cell-depleted PBSCT is a feasible alternative for
      treating graft failure after UCBT.

PMID- 24685579
TI  - Full endoscopic endonasal transclival approach: meningioma attached to the
      ventral surface of the brainstem.
AB  - BACKGROUND: Intracranial meningiomas without dural attachment (MWODA) are rare
      entities. We present the first case published, to the best of our knowledge,
      regarding a MWODA attached to the ventral surface of the brainstem. This location
      makes the patient subsidiary to treatment through an expanded endonasal
      transclival approach. CLINICAL PRESENTATION: A 16-year-old female with suspected
      diagnosis of recurrence of a clear cell meningioma (CCM) at a distance from the
      initial lesion, located on the premedullary cistern. The patient underwent a pure
      endoscopic low transclival approach. The attachment to the ventral surface of the
      brainstem was confirmed intraoperatively. Postoperative MRI confirmed gross total
      resection and treatment was complemented with adjuvant fractionated stereotactic
      radiotherapy. No complications related to the procedure were observed.
      CONCLUSION: MWODA may appear attached to the ventral brainstem. The expanded
      endonasal approach to the clivus provides a critical anatomical advantage in the
      treatment of medial lesions, even ventral meningiomas, to the lower cranial
      nerves. Reconstruction principles must be strictly respected to reduce
      complications.

PMID- 24685580
TI  - Matriptase is required for the active form of hepatocyte growth factor induced
      Met, focal adhesion kinase and protein kinase B activation on neural
      stem/progenitor cell motility.
AB  - Hepatocyte growth factor (HGF) is a chemoattractant and inducer for neural
      stem/progenitor (NS/P) cell migration. Although the type II transmembrane serine
      protease, matriptase (MTP) is an activator of the latent HGF, MTP is
      indispensable on NS/P cell motility induced by the active form of HGF. This
      suggests that MTP's action on NS/P cell motility involves mechanisms other than
      proteolytic activation of HGF. In the present study, we investigate the role of
      MTP in HGF-stimulated signaling events. Using specific inhibitors of
      phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt) or focal adhesion
      kinase (FAK), we demonstrated that in NS/P cells HGF-activated c-Met induces PI3k
      Akt signaling which then leads to FAK activation. This signaling pathway
      ultimately induces MMP2 expression and NS/P cell motility. Knocking down of MTP
      in NS/P cells with specific siRNA impaired HGF-stimulation of c-Met, Akt and FAK
      activation, blocked HGF-induced production of MMP2 and inhibited HGF-stimulated
      NS/P cell motility. MTP-knockdown NS/P cells cultured in the presence of
      recombinant protein of MTP protease domain or transfected with the full-length
      wild-type but not the protease-defected MTP restored HGF-responsive events in
      NS/P cells. In addition to functioning as HGF activator, our data revealed novel
      function of MTP on HGF-stimulated c-Met signaling activation. 

PMID- 24685581
TI  - Leptin downregulates LPS-induced lung injury: role of corticosterone and insulin.
AB  - BACKGROUND/AIMS: We investigated the effects of leptin in the development of
      lipopolysaccharide (LPS)-induced acute lung inflammation (ALI) in lean mice.
      METHODS: Mice were administered leptin (1.0ug/g) or leptin (1.0ug/g) followed by
      LPS (1.5ug/g) intranasally. Additionally, some animals were given LPS (1.5ug/g)
      or saline intranasally alone, as a control. Tissue samples and fluids were
      collected six hours after instillation. RESULTS: We demonstrated that leptin
      alone did not induce any injury. Local LPS exposure resulted in significant acute
      lung inflammation, characterized by a substantial increase in total cells, mainly
      neutrophils, in bronchoalveolar lavages (BAL). We also observed a significant
      lymphocyte influx into the lungs associated with enhanced lung expression of
      chemokines and cytokines (KC, RANTES, TNF-alpha, IFN-gamma, GM-CSF and VEGF). LPS
      induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in
      the lungs. Mice that received LPS showed an increase in insulin levels. Leptin,
      when administered prior to LPS instillation, abolished all of these effects. LPS
      induced an increase in corticosterone levels, and leptin potentiated this event.
      CONCLUSION: These data suggest that exogenous leptin may promote protection
      during sepsis, and downregulation of the insulin levels and upregulation of
      corticosterone may be important mechanisms in the amelioration of LPS-induced
      ALI.

PMID- 24685582
TI  - Genotoxic assessment of Rubus imperialis (Rosaceae) extract in vivo and its
      potential chemoprevention against cyclophosphamide-induced DNA damage.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rubus imperialis Cham. Schl. (Rosaceae) is
      frequently used in traditional medicine as hypoglycemic, antinociceptive and
      antiviral remedy. MATERIALS AND METHODS: Swiss albino mice were distributed in
      eight groups for acute treatment with Rubus imperialis extract (24 h). The
      extract doses selected were 50, 250 and 500 mg/kg b.w. administered by gavage
      alone or plus to CPA (50 mg/kg b.w.) administered by intraperitoneal injection.
      Control groups were treated in a similar way. Analyses were performed using the
      comet assay, on leukocytes (collected 4 and 24h after treatment) and liver
      (collected 24 h after treatment), and using the micronucleus test (MN) in bone
      marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic
      (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). RESULTS AND
      CONCLUSION: The main compounds identified in the Rubus imperialis extract were
      saponins and steroidal compounds, with niga-ichigoside and tormentic acid being
      the major compounds. Tested doses of Rubus imperialis extract showed no genotoxic
      effects on leukocytes from peripheral blood or liver cells by the comet assay.
      However, the MN test showed an increase in the frequency of micronucleated cells
      at the two higher doses tested, indicating that this extract has
      clastogenic/aneugenic effects on bone marrow cells at higher doses. On the other
      hand, for all cells evaluated, the three tested doses of the Rubus imperialis
      extract promoted inhibition of DNA damage induced by CPA. Despite the
      chemoprevention observed, the clastogenicity/aneugenicity observed suggested
      caution about either continuous or high-dose usage of Rubus imperialis aerial
      parts extract by humans.

PMID- 24685583
TI  - Ethnobotanical survey of medicinal plants used by people in Oriental Morocco to
      manage various ailments.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This document presents the uses of plants in
      traditional herbal medicines in Oriental Morocco. It also determines the
      homogeneity of informant knowledge in medicinal plants suitable for different
      ailment categories and the most preferred plant species used to treat each
      illness category in the study area. MATERIALS AND METHODS: The ethnobotanical
      information was obtained from 3151 inhabitants who were 20 years and older in
      five different areas of Oriental Morocco region. The data were analyzed through
      informant consensus factor (ICF) and frequency of uses (FC). RESULTS: The results
      indicated that 65.7% of the participants interviewed used medicinal plants to
      treat 23 ailments. The inventory of medicinal plants is summarized in a synoptic
      table, which contains the scientific and vernacular names of the plant, the part
      of the plant and the preparation used and the therapeutic indication. Extensive
      investigations have brought to light 148 medicinal plants belonging to 60
      families; of these, 108 are used for the disorders of the digestive system, 74
      for diabetes, 73 for dermatological problems, 66 for allergy, 66 for
      cardiovascular disorders and 63 for respiratory problems. In this region, the
      most frequently used plants including Origanum compactum Benth., Trigonella
      foenum graecum L., Lavandula dentata L., Mentha pulegium L., Nigella sativa L.,
      Rosmarinus officinalis L., Lippia citriodora L., Tetraclinis articulata Benth.,
      and Atemisia herba-alba Asso. Lamiaceae and Asteraceae are the dominant locally
      used families. Most medicines were prepared in the form of powder and used
      orally. Leaves were the most frequently used plant part. Gastro-intestinal
      ailments have high ICF (0.92) whereas pathologies of the circulatory and
      ophthalmological uses have low ICF (0.22 and 0.24, respectively). CONCLUSION:
      Oriental Morocco boasts an extensive phytotherapy knowledge base and ICF values
      indicated that there was high agreement in the use of plants in gastro-intestinal
      ailment category among the users. The frequency use value (FC) indicated that
      these plants are the most preferred species used in study areas. These preferred
      plant species could be prioritized for conservation and subjected to further
      studies related to chemical screening for their authenticity.

PMID- 24685584
TI  - Interaction of five anthraquinones from rhubarb with human organic anion
      transporter 1 (SLC22A6) and 3 (SLC22A8) and drug-drug interaction in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is a well-known traditional Chinese
      medicine and has been used in China for thousands of years. Anthraquinone
      derivatives including rhein, emodin, aloe-emodin, chrysophanol and physcion are
      the important components in rhubarb. MATERIALS AND METHODS: Here we studied the
      interaction of five anthraquinone derivatives with human renal organic anion
      transporter 1 (hOAT1) and hOAT3 stably expressed in cells, and interaction of
      rhein or rhubarb extract (RE) with furosemide (FS, substrate of OATs) in rats.
      RESULTS: Uptake of 6-carboxyl fluorescein via hOAT1 and fluorescein via hOAT3
      were markedly inhibited by rhein, emodin and aloe-emodin, and slightly inhibited
      by chrysophanol and physcion. The estimated IC50 values for rhein, emodin, aloe
      emodin and probenecid (typical inhibitor of hOAT1 and hOAT3) were 0.23, 0.61,
      2.29 and 18.34 MUM for hOAT1, and 0.08, 1.22, 5.37 and 5.83 MUM for hOAT3,
      respectively. Furthermore, the data from the cellular accumulation assay
      indicated that these five compounds were not substrates of hOAT1 or hOAT3.
      Pharmacokinetic interaction between rhein and FS in rats showed that area under
      the curve (AUC0-t) for FS was increased by 65% when coadministrated with rhein.
      RE was also used to interact with FS in rats and results showed that AUC0-t of FS
      was increased by 32% and by 52% when coadministrated with single-dose or multiple
      dose of RE, respectively. CONCLUSIONS: These findings suggested that five
      anthraquinones inhibited hOAT1 and hOAT3, but these compounds were not
      transported by hOAT1 or hOAT3. Furthermore, rhein or RE, might cause drug-drug
      interaction when coadministrated with substrates of OAT1 or OAT3 in vivo.

PMID- 24685585
TI  - A metabolic profiling analysis of the acute toxicological effects of the realgar
      (As2S2) combined with other herbs in Niuhuang Jiedu Tablet using 1H NMR
      spectroscopy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Niuhuang Jiedu Tablet (NJT), composed of Realgar
      (As2S2), Bovis Calculus Artificialis, Borneolum Synthcticum, Gypsum Fibrosum,
      Rhei Radix et Rhizoma (RR), Scutellariae Radix (SR), Platycodonis Radix (PR) and
      Glycyrrhizae Radix et Rhizoma (GR), is an effective formula of traditional
      Chinese medicine (TCM) used in treating acute tonsillitis, pharyngitis,
      periodontitis and mouth ulcer. In the formula, significant level of realgar
      (As2S2) as a potentially toxic element is contained. In our pervious experiments,
      NJT was significantly less toxic than realgar (As2S2), and the material bases of
      toxicity alleviation effect to realgar (As2S2) were RR, SR, PR and GR. However,
      the toxicity alleviation effect of each above mentioned four herbs to realgar
      (As2S2) and their synergistic detoxification effects to realgar (As2S2) were
      still obscure. MATERIALS AND METHODS: Male Wistar rats were divided into 11
      groups: control, group R (treated with Realgar), group RRSPG (treated with
      Realgar, RR, SR, PR and GR), group RRSP (treated with Realgar, RR, SR and PR),
      group RRSG (treated with Realgar, RR, SR and GR), group RRPG (treated with
      Realgar, RR, PR and GR), group RSPG (treated with Realgar, SR, PR and GR), group
      RR (treated with Realgar and RR), group RS (treated with Realgar and SR), group
      RP (treated with Realgar and PR) and group RG (treated with Realgar and GR).
      Based on (1)H NMR spectra of urine and serum from rats, PCA and PLS-DA were
      performed to identify different metabolic profiles. Liver and kidney
      histopathology examinations and serum clinical chemistry analysis were also
      performed. RESULTS: The metabolic profiles of groups RR, RS, RP and RG were
      similar to those of group R, while the metabolic profiles of groups RRSPG, RRSP,
      RRSG, RRPG and RSPG were almost in line with those of control group. Statistics
      results were confirmed by the histopathological examination and biochemical
      assay. CONCLUSION: The present work suggested that the toxicity alleviation
      effects of RR, SR, PR and GR to realgar (As2S2) were not obvious when combined
      with realgar (As2S2) respectively, but they had synergistic detoxification
      effects on realgar (As2S2) mutually.

PMID- 24685586
TI  - 1H NMR-based metabonomic analysis of the effect of optimized rhubarb aglycone on
      the plasma and urine metabolic fingerprints of focal cerebral ischemia
      reperfusion rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The ischemia cerebrovascular disease is one of
      leading causes of death and long-term disability in modern society. Rhubarb is
      one of the common traditional Chinese medicine with many effects, and the main
      pharmacodynamic ingredients are aloe-emodin, rhein, emodin, chrysophanol and
      physcion. The five components are also known as rhubarb aglycone. Rhubarb
      aglycone has been confirmed to play a remarkable curative effect on cerebral
      ischemia, but the mechanism is not clear. In this study, (1)H NMR-based
      metabonomics approach has been used to investigate the protective effect of the
      optimized rhubarb aglycone on rats of cerebral ischemia-reperfusion. MATERIALS
      AND METHODS: Male Wistar rats were divided into four groups: sham operation
      group, model group, Nimodipine group and the optimized rhubarb aglycone group.
      Based on (1)H-NMR spectra of plasma and urine, principal component analyses were
      performed to identify different metabolic markers and explore the changes of
      associated biochemical pathways. Behavior research and brain histopathology
      examinations were also performed. RESULTS: It was showed that the optimized
      rhubarb aglycone treatment improved neurological deficits, cerebral infarction
      and neuronal apoptosis. Principal component analysis scores plots demonstrated
      that the cluster of model rats was separated from those of sham operation group;
      rats of the optimized rhubarb aglycone group were classified from model group,
      but the optimized rhubarb aglycone group closed to the sham operation group.
      Optimized rhubarb aglycone regulated the associated amino acid, energy and lipid
      metabolisms disturbed in model rats. CONCLUSION: Our results suggested that the
      optimized rhubarb aglycone had protective effect on rats of cerebral ischemia
      reperfusion and explored the metabolic regulation mechanism. This work showed
      that the NMR-based metabonomics approach might be a promising approach to study
      mechanisms of traditional Chinese medicines.

PMID- 24685587
TI  - Antioxidant effects of Genkwa flos flavonoids on Freund's adjuvant-induced
      rheumatoid arthritis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Genkwa flos (Daphne genkwa Sieb. et Zucc.), a
      Chinese herbal medicine, has been traditionally used for over two thousand years
      in China for inflammation related symptoms, including joint pain. To evaluate the
      antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on
      adjuvant arthritis in rats and to identify the relationship between antioxidant
      potential and whole blood viscosity (WBV). MATERIALS AND METHODS: FA compounds
      were identified using LC-MS and the content was assayed by HPLC. Arthritis was
      induced by an intradermal injection of Freund's complete adjuvant in the footpad.
      The effects of FA on paw volumes, secondary arthritis scores, histopathology of
      joints, and body and organ weights were measured. The antioxidant effects of FA
      and WBV were determined. RESULTS: LC-MS analysis showed that the FA contained
      four major compounds: luteolin, apigenin, hydroxygenkwanin and genkwanin. FA
      significantly decreased paw edema, arthritis scores, and weight loss. These
      observations were consistent with the reduction of oxidative stress and the
      improvement of the WBV. CONCLUSION: FA significantly decreased arthritis in a rat
      model through antioxidant and hemorheological modulatory mechanisms. The Genkwa
      flos flavonoids may have clinical potential for the treatment of rheumatoid
      arthritis.

PMID- 24685588
TI  - An ethnobotanical study of medicinal plants used in sacred groves of Kumaon
      Himalaya, Uttarakhand, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: International organizations recognize the
      importance of sacred groves and place them into the context of sustainable
      development and also emphasize to conserve biodiversity through protection of
      sacred groves and sties. The significance of medicinal plants from Himalayan
      region is well known to the world. Therefore, present study was conducted in
      identified sacred groves of Kumaon Himalaya to investigate and document the
      utilization of medicinal plants by various local communities and tribal people.
      MATERIALS AND METHODS: The study was conducted during 2008-2011 in four seasons
      of the year. Information was collected from 70 locals from different sacred
      groves by using free listing interviews with randomly selected informants and
      semi-structured questionnaires; plant specimens were collected, identified and
      deposited at the CSIR-NBRI herbarium (LWG), Lucknow, India. RESULTS: Seven sacred
      groves viz., Dhwaj, Haat Kali, Hokra, Malay Nath, Nakuleshwar, Narayan Swami
      Ashram and Patal Bhuvneshwar were identified from the Pithoragarh district of
      Kumaon Himalaya. 89 medicinal plants belonging to 52 families and 77 genera of
      which, 2 are lichens, 4 are pteridophytes, 3 are gymnosperms and remaining 80
      plant species are angiosperms. 6 plant species are reported with new therapeutic
      uses for the first time in this paper. Highest informant's consensus factor value
      was found in liver disorder (0.55) and least by body pains (0.23). 55
      ethnomedicinal plants are showing 100% fidelity level against various diseases.
      CONCLUSION: Sacred groves in Kumaon region of Indian Himalaya are rich sources
      and best repository of ethno-medicinally important plants with many rare,
      endangered and threatened species. It is an excellent example of unique
      traditional way of in situ conservation of different plant species.

PMID- 24685589
TI  - Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced
      inflammatory responses in RAW264.7 macrophages.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rheum rhabarbarum (rhubarb) has long been used
      for the treatment of inflammation in China and other Asian countries. However,
      the mechanism underlying the anti-inflammatory activity of this medicinal plant
      is not fully understood. The present study was designed to investigate the anti
      inflammatory effects of anthraquinones, the major constituents in rhubarb, and
      the molecular mechanism involved in their anti-inflammatory effects. MATERIALS
      AND METHODS: RAW264.7 cells were stimulated by lipopolysaccharide (LPS) in the
      presence or absence of the compounds examined. The proliferation of RAW264.7
      cells was assayed by the Alamar-Blue method. The quantity of nitric oxide (NO)
      was determined by Griess assay. The expression of pro-inflammatory cytokines was
      determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real
      time PCR. Inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor
      kappaBalpha (IkappaBalpha), extracellular signal-regulated kinase (ERK), p38
      mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), and
      Akt/phosphoinositide 3-kinase (PI3K) protein expression levels were determined by
      Western blotting. RESULTS: Aloe-emodin markedly suppressed the production of NO,
      interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) in LPS-stimulated RAW264.7
      cells with no apparent cytotoxicity. The mRNA expression levels of iNOS, IL-6,
      and IL-1beta genes were also significantly inhibited by aloe-emodin. Western blot
      analysis showed that aloe-emodin suppressed LPS-induced iNOS protein expression,
      IkappaBalpha degradation, and the phosphorylation of ERK, p38, JNK, and Akt.
      CONCLUSIONS: These results demonstrate that aloe-emodin is the bioactive
      component of rhubarb that confers an anti-inflammatory effect through a likely
      mechanism involving a decrease in pro-inflammatory cytokine production in LPS
      induced RAW264.7 macrophages via inhibition of NF-kappaB, MAPK, and PI3K
      pathways.

PMID- 24685590
TI  - Comparison of the theoretical and real-world evolutionary potential of a genetic
      circuit.
AB  - With the development of next-generation sequencing technologies, many large scale
      experimental efforts aim to map genotypic variability among individuals. This
      natural variability in populations fuels many fundamental biological processes,
      ranging from evolutionary adaptation and speciation to the spread of genetic
      diseases and drug resistance. An interesting and important component of this
      variability is present within the regulatory regions of genes. As these regions
      evolve, accumulated mutations lead to modulation of gene expression, which may
      have consequences for the phenotype. A simple model system where the link between
      genetic variability, gene regulation and function can be studied in detail is
      missing. In this article we develop a model to explore how the sequence of the
      wild-type lac promoter dictates the fold-change in gene expression. The model
      combines single-base pair resolution maps of transcription factor and RNA
      polymerase binding energies with a comprehensive thermodynamic model of gene
      regulation. The model was validated by predicting and then measuring the
      variability of lac operon regulation in a collection of natural isolates. We then
      implement the model to analyze the sensitivity of the promoter sequence to the
      regulatory output, and predict the potential for regulation to evolve due to
      point mutations in the promoter region. 

PMID- 24685591
TI  - The emerging role of the inflammasome in kidney diseases.
AB  - PURPOSE OF REVIEW: To focus on the latest data that elucidate the role of the
      NLRP3 inflammasome in kidney diseases. RECENT FINDINGS: The NLRP3 inflammasome is
      not limited by the traditional microbial stimuli of innate immunity and its
      connection with autophagy, apoptosis, fibrosis, and pro-inflammatory cytokines
      has broader implications for a variety of kidney diseases. In a wide spectrum of
      glomerular and tubulointerstitial diseases, the NLRP3 inflammasome is upregulated
      in both classical immune cells such as infiltrating macrophages and resident
      dendritic cells as well as in renal tubular epithelial cells, and even podocytes.
      Inhibition of the NLRP3 inflammasome ameliorates renal injury in a variety of
      animal models. Interestingly, this extends to models of proteinuria, which
      suggests that the deleterious effect of albuminuria on the proximal tubular
      epithelium and podocytes is, in part, mediated by inflammasome activation.
      SUMMARY: Recent studies in animal models, and limited studies in humans, suggest
      a broad role for inflammasome activation in renal disease. Surprisingly,
      individual components of the inflammasome, independent of inflammasome
      activation, may also contribute to progressive renal injury. Additional, studies
      are needed to define the relative importance of the inflammasome in specific
      diseases and the therapeutic opportunities afforded by targeting the
      inflammasome.

PMID- 24685592
TI  - An EASO position statement on multidisciplinary obesity management in adults.
AB  - Obesity has proven to be a gateway to ill health. It has already reached epidemic
      proportions becoming one of the leading causes of death and disability in Europe
      and world-wide. Obesity plays a central role in the development of a number of
      risk factors and chronic diseases like hypertension, dyslipidaemia and type 2
      diabetes mellitus inducing cardiovascular morbidity and mortality. Therefore
      weight management plays a central role in controlling the respective risk factors
      and their consequences. Obesity is a complex condition of multifactorial origin.
      Biological but also psychological and social factors interfere to lead to excess
      body weight and its deleterious outcomes. Obesity management cannot focus any
      more only on weight (and BMI) reduction. More attention is to be paid to waist
      circumference (or waist-to-hip ratio, especially in females), the improvement in
      body composition (measured with body composition tracking systems like BOD POD,
      dual energy X-ray absorptiometry or bioelectrical impedance analysis) which is
      focusing on ameliorating or maintaining fat-free mass and decreasing fat mass.
      Management of co-morbidities, improving quality of life and well-being of obese
      patients are also included in treatment aims. This statement emphasises the
      importance of a comprehensive approach to obesity management.

PMID- 24685593
TI  - Simultaneous determination of sildenafil citrate and some nitric oxide releasing
      drugs in human plasma using UPLC MS/MS.
AB  - OBJECTIVE: The inadvertent combination of sildenafil (SLD) and nitric oxide
      releasing compounds (NRC) may cause a life threatening hypotension and conversion
      of coital angina into an irreversible one. The aim of this study was to develop
      and validate a UPLC MS/MS method for the simultaneous quantitative analysis of
      SLD, nicorandil (NRD), and ARG in human plasma to determine the safety margins
      for drug combinations. DESIGN AND METHOD: Chromatographic elution was achieved in
      4min using gradient elution and an injection volume of 10MUL. Electro-spray
      positive ionization (ESI+ve) detection and multiple-reaction monitoring mode
      (MRM) were used for detection. RESULTS: The method was found to be linear (10
      900ng/mL for SLD and NRD while 1-30MUg/mL for ARG), accurate and precise (99.35+/
      1.58, 99.62+/-1.13, and 100.04+/-1.22% for SLD, NRD and ARG; respectively) and
      met all other validation requirements. CONCLUSION: The developed UPLC MS/MS
      method is suitable for fast, sensitive, accurate and simultaneous determinations
      of SLD, NRD, and ARG in plasma.

PMID- 24685594
TI  - GSTM1-null and GSTT1-null genotypes are associated with essential arterial
      hypertension in patients with type 2 diabetes.
AB  - OBJECTIVE: To evaluate whether the genetic polymorphisms of glutathione S
      transferases M1 (GSTM1) and T1 (GSTT1), Ile105Val of the GSTP1 (rs947894), and
      the Val16Ala polymorphism of the MnSOD (rs4880) are associated with essential
      arterial hypertension (EAH) in Caucasians with type 2 diabetes. DESIGN AND
      METHODS: 1015 Slovenian subjects (Caucasians) with type 2 diabetes with/without
      EAH were enrolled in the cross-sectional study. Genotypes were determined by
      multiplex PCR amplification and PCR-restriction fragment length polymorphism
      method. RESULTS: In the cross-sectional study, GSTM1-null genotype and GSTT1-null
      genotype were associated with EAH in subjects with type 2 diabetes (59.0% vs.
      50.3%, p=0.007; 28.5% vs. 20.7%, p=0.008; consequently). CONCLUSION: After
      adjustment for age, body mass index, and hsCRP level, GSTM1-null and GSTT1-null
      genotypes were found to be independent risk factors for the development of EAH in
      Slovenian patients with type 2 diabetes.

PMID- 24685595
TI  - tassel-less1 encodes a boron channel protein required for inflorescence
      development in maize.
AB  - tassel-less1 (tls1) is a classical maize (Zea mays) inflorescence mutant.
      Homozygous mutant plants have no tassels or very small tassels, and ear
      development is also impaired. Using a positional cloning approach, ZmNIP3;1 (a
      NOD26-like intrinsic protein) was identified as the candidate gene for tls1. The
      ZmNIP3;1 gene is completely deleted in the tls1 mutant genome. Two Mutator
      insertional TUSC alleles of ZmNIP3;1 exhibited tls1-like phenotypes, and allelism
      tests confirmed that the tls1 gene encodes ZmNIP3;1. Transgenic plants with an
      RNA interference (RNAi) construct to down-regulate ZmNIP3;1 also showed tls1-like
      phenotypes, further demonstrating that TLS1 is ZmNIP3;1. Sequence analysis
      suggests that ZmNIP3;1 is a boron channel protein. Foliar application of boron
      could rescue the tls1 phenotypes and restore the normal tassel and ear
      development. Gene expression analysis indicated that in comparison with that of
      the wild type or tls1 plants treated with boron, the transition from the
      vegetative to reproductive phase or the development of the floral meristem is
      impaired in the shoot apical meristem of the tls1 mutant plants. It is concluded
      that the tls1 mutant phenotypes are caused by impaired boron transport, and boron
      is essential for inflorescence development in maize. 

PMID- 24685596
TI  - European inter-institutional impact study of MammaPrint.
AB  - AIM: To measure the impact of MammaPrint on adjuvant treatment decisions and to
      analyze the agreement in treatment decisions between hospitals from 4 European
      countries for the same patient cohort. METHODS: Breast cancer patients were
      prospectively enrolled and MammaPrint was assessed. Patients' clinical data
      without and then with MammaPrint results were sent to the different
      multidisciplinary teams and treatment advice was provided for each patient.
      RESULTS: Using MammaPrint, chemotherapy treatment advice for ER+/HER2- breast
      cancer patients was changed in 37% of patients by the Dutch, 24% by the Belgian,
      28% by the Italian and 35% by the Spanish teams. MammaPrint increased the inter
      institutional agreement in treatment advice (chemotherapy or no chemotherapy)
      from 51% to 75%. CONCLUSION: The results of this study indicate that MammaPrint
      impacts adjuvant chemotherapy recommendation. MammaPrint can decrease inter
      institutional and inter-country variability in adjuvant treatment advice for
      breast cancer patients.

PMID- 24685597
TI  - Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6
      poor metabolizer phenotype.
AB  - BACKGROUND: CYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into
      its main active metabolite, endoxifen. Poor CYP2D6 metabolizers (PM) have lower
      endoxifen plasma concentrations and possibly benefit less from treatment with
      tamoxifen. We evaluated tamoxifen dose adjustment in CYP2D6 PM patients in order
      to obtain plasma concentrations of endoxifen comparable to patients with
      extensive CYP2D6 metabolism (EM). PATIENTS AND METHODS: Comprehensive CYP2D6
      genotyping and plasma tamoxifen metabolite concentrations were performed among
      249 breast cancer patients in adjuvant treatment with tamoxifen. Tamoxifen dose
      was increased in PM patients to 40 mg and to 60 mg daily for a 4-month period
      each, repeating tamoxifen metabolite measurements on completion of each dose
      increase. We compared the endoxifen levels between EM and PM patients, and among
      the PM patients at each dose level of tamoxifen (20, 40 and 60 mg). RESULTS:
      Eleven PM patients (4.7%) were identified. The mean baseline endoxifen
      concentration in EM patients (11.30 ng/ml) was higher compared to the PM patients
      (2.33 ng/ml; p < 0.001). In relation to the 20 mg dose, increasing the tamoxifen
      dose to 40 and 60 mg in PM patients significantly raised the endoxifen
      concentration to 8.38 ng/ml (OR 3.59; p = 0.013) and to 9.30 ng/ml (OR 3.99; p =
      0.007), respectively. These concentrations were comparable to those observed in
      EM patients receiving 20 mg of tamoxifen (p = 0.13 and p = 0.64, respectively).
      CONCLUSION: In CYP2D6 PM patients, increasing the standard tamoxifen dose two
      fold or three-fold raises endoxifen concentrations to levels similar to those of
      patients with EM phenotype.

PMID- 24685598
TI  - [Recovery of elbow flexion in post-traumatic C5-C6 and C5-C6-C7 palsy:
      retrospective dual-center study comparing single and double nerve transfer].
AB  - Twenty-nine patients underwent single (n=15) or double (n=14) nerve transfer for
      post-traumatic elbow flexion palsy. Patients averaged 30.2 years, with a mean
      preoperative delay of six months and postoperative follow-up of 34.2 months.
      Sixty per cent of the single transfer patients recovered to BMRC grade M4 after
      an average of follow-up of 13.2 months. Eighty-five percent of double nerve
      transfer patients reached grade M4 after an average follow-up of 11 months. There
      were no significant differences between groups. Clinical assessment revealed
      motor or sensory deficit in seven cases, which did not cause any impairment.
      Patients with a C5-C6 injury had shorter recovery times and better strength in
      comparison with those with C5-C6-C7 injury. By restoring shoulder function, elbow
      flexion will be indirectly improved. This improvement can be partially attributed
      to the base of the arm being more stable.

PMID- 24685599
TI  - Extraoral plasmablastic lymphoma detected using ascitic fluid cytology and flow
      cytometry: a case report with a review of the literature.
AB  - BACKGROUND: Plasmablastic lymphoma (PL) is a relatively new category of lymphoma,
      which has been considered to be found predominantly in the oral cavity and has a
      strong association with HIV. CASE: We report a case of extraoral/mesenteric PL
      detected using cytological examination of ascitic fluid assisted by flow
      cytometric (FC) analysis. The cells were positive for CD38, CD138, CD10, CD45 and
      CD56 and negative for CD3, CD19, CD20 and CD79a, with cytoplasmic lambda light
      chain restriction. We also reviewed 67 cases of extraoral PL from the available
      literature and found them to be less often associated with HIV (than oral PL),
      occurring mostly in males aged 30-60 years, with the most common extraoral site
      being the anorectal region. CONCLUSION: A high index of suspicion at the level of
      the cytopathologist is imperative for identifying lymphoma cells in a body fluid.
      A rare entity like PL can also be diagnosed on cytology assisted by ancillary
      techniques (like FC), without the need for a biopsy. We also suggest that the
      minimum panel to diagnose PLs should include CD138, MUM-1, Ki-67, ALK-1, CD3,
      immunoglobulin light-chains, CD20 and PAX5.

PMID- 24685600
TI  - Comparative genomics study for the identification of drug and vaccine targets in
      Staphylococcus aureus: MurA ligase enzyme as a proposed candidate.
AB  - Now-a-days increasing emergence of antibiotic-resistant pathogenic microorganisms
      is one of the biggest challenges for management of disease. In the present study
      comparative genomics, metabolic pathways analysis and additional parameters were
      defined for the identification of 94 non-homologous essential proteins in
      Staphylococcus aureus genome. Further study prioritized 19 proteins as vaccine
      candidates where as druggability study reports 34 proteins suitable as drug
      targets. Enzymes from peptidoglycan biosynthesis, folate biosynthesis were
      identified as candidates for drug development. Furthermore, bacterial secretory
      proteins and few hypothetical proteins identified in our analysis fulfill the
      criteria of vaccine candidates. As a case study, we built a homology model of one
      of the potential drug target, MurA ligase, using MODELLER (9v12) software. The
      model has been further selected for in silico docking study with inhibitors from
      the DrugBank database. Results from this study could facilitate selection of
      proteins for entry into drug design and vaccine production pipelines. 

PMID- 24685601
TI  - Development of an allele-specific PCR for Escherichia coli B2 sub-typing, a rapid
      and easy to perform substitute of multilocus sequence typing.
AB  - We developed and validated an allele-specific PCR method for detecting the nine
      main Escherichia coli phylogroup B2 lineages involved in extra-intestinal
      infections, which could be used as a substitute for multilocus sequence typing in
      studies for which the greater resolution at the sequence type level is not
      needed. 

PMID- 24685602
TI  - Severe fibrosis in patients with recurrent hepatitis C after liver
      transplantation: a French experience on 250 patients over 15 years (the Orfevre
      study).
AB  - BACKGROUND AND AIMS: Recurrent hepatitis C after liver transplantation (LT) is
      associated with rapid fibrosis progression. The aim of this study was to evaluate
      the cumulative risk for severe fibrosis and the factors influencing it. PATIENTS
      AND METHODS: Two hundred and fifty LT patients were included 1 to 15years after
      LT. Recurrence of chronic hepatitis C on liver graft was classified according to
      Metavir score. RESULTS: Kaplan-Meyer estimates for actuarial progression to
      severe fibrosis (Metavir>F3) showed a probability of 15.2% and 44.5% at 5 and
      10years, respectively. Predictive factors for progression to severe fibrosis
      were: use of tacrolimus as main CNI, recipient age at time of biopsy<55, donor
      age >=45, graft HCV re-infection<3months, biologically suspected graft re
      infection and lack of response to antiviral treatment after LT. Multivariate
      analysis disclosed that only donor age >=45 (hazard ratio 2.243, 95%CI 1.264
      3.983, P=0.0058) and lack of response to antiviral treatment (hazard ratio 2.816,
      95%CI 1.227-6.464, P=0.0146) were associated to severe fibrosis. CONCLUSIONS: Our
      study confirms that donor age >=45 and lack of response to antiviral treatment
      after LT are major predictive factors of progression of HCV recurrence on liver
      graft.

PMID- 24685603
TI  - Thymidylate synthase genetic polymorphisms and colorectal cancer risk: a meta
      analysis.
AB  - AIM: The effects of thymidylate synthase (TS) polymorphisms on susceptibility to
      colorectal cancer (CRC) have been investigated in many studies, but the results
      remain conflicting rather than conclusive. To resolve these conflicts, we
      performed a quantitative synthesis of the evidence on the association between
      these two polymorphisms and CRC risk. METHODS: All eligible case-control studies
      published up to September 2013 were identified by searching PubMed, Web of
      Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval
      (95% CI) were calculated by using a fixed- or random-effect model. RESULTS: A
      total of 11 case-control studies were included, including 10 studies (3324 cases
      and 4622 controls) for TSER polymorphism and 9 studies (3223 cases and 3886
      controls) for TS1494del6 polymorphism. Overall, no significant association
      between the TS polymorphisms and CRC risk was found. In the subgroup analysis by
      ethnicity, a significantly association were found among Caucasian populations for
      TSER polymorphism; but for TS1494del6 polymorphism, no significantly association
      was observed in both Asian and Caucasian populations. When stratifying by source
      of controls, we found there was a statistically significant association between
      TSER polymorphism and risk of CRC in the population-based population; however, we
      detected no association in both population-based and hospital-based populations
      for TS1494del6 polymorphism. CONCLUSIONS: This meta-analysis suggests that the
      TSER polymorphism in TS gene but not TS1494del6 polymorphism might be a
      protective factor for CRC among Caucasian populations.

PMID- 24685604
TI  - High frequency home-based exercise decreases levels of vascular endothelial
      growth factor in patients with stable angina pectoris.
AB  - BACKGROUND: In coronary artery disease (CAD), circulating angiogenic factors have
      been seen to increase, possibly as a response to ischaemia. Regular physical
      activity (PA) is recommended for prevention and treatment of CAD, but more
      research is needed to optimise PA regimes. We investigated the effect of home
      based high frequency exercise (HFE) on angiogenic cytokines and cardiac markers
      in patients with stable CAD. DESIGN: This was a randomised case-control study
      METHODS: Sixty-two patients, with stable CAD, were randomised to HFE (n = 33),
      (aerobic exercise 70% of max, 30 min, five times/week and resistance exercise
      three times/week), performed at home, or usual lifestyle (control, n = 29). After
      eight weeks, percutaneous coronary intervention (PCI) was performed in both
      groups, and the HFE group continued another six months of exercise. Serum
      vascular endothelial growth factor (VEGF) and stromal derived factor-1 (SDF-1),
      plasma N-terminal-brain natriuretic peptide (NT-proBNP), high-sensitive troponin
      T (TnT) and copeptin were analysed. RESULTS: Data are presented as median
      (25(th), 75(th) percentile) of relative changes (%) from baseline. Values of p
      are given for the difference between the HFE and controls. HFE decreased
      circulating VEGF levels, before PCI (-5% (-15%, -2%)), while VEGF levels
      increased in the control group (5% (-3%, 20%) p = 0.004). A significant
      difference in VEGF remained at three months post-PCI (HFE (-1%(-12%, 5%), control
      (7% (0%, 14%), p = 0.04), but not at six months after PCI. SDF-1, NT-proBNP, TnT
      and copeptin levels did not differ significantly. In addition, VEGF levels were
      positively correlated to NT pro-BNP. CONCLUSIONS: Home-based HFE decreased
      circulating VEGF in patients with stable CAD, suggesting a reduced ischaemic
      burden. HFE does not increase markers of cardiac dysfunction, suggesting that it
      is a safe therapeutic intervention in these patients.

PMID- 24685605
TI  - Evaluation of oral anticoagulation therapy: rationale and design of the
      thrombEVAL study programme.
AB  - BACKGROUND: Since decades, oral anticoagulation (OAC) with vitamin K antagonists
      (VKA) is an established therapy for both prevention and treatment of
      thromboembolism in daily clinical routine. Increasing life expectancy,
      demographic changes, and novel oral anticoagulants have led to an increasing
      complexity of medical therapy. However, data on quality and management of VKA
      therapy with phenprocoumon in current medical care are limited. Our aim is to
      investigate the quality of OAC with VKA in current health care and to evaluate
      the potential for improvements. STUDY DESIGN: The investigator-initiated
      thrombEVAL study programme comprises two cohorts of patients treated with vitamin
      K antagonists for oral anticoagulation therapy in real-life settings: a
      multicentre cohort of patients in regular medical care and a multilocal, single
      centre cohort of patients in a telemedicine-based coagulation service. The study
      programme is expected to enrol a total number of approximately 2000 to 2500
      patients. Both cohorts will build on a detailed clinical assessment of
      participants and anticoagulation therapy at study enrolment. Subsequently active
      and passive follow-up investigations are carried out to document and validate
      complications of the treatment. The primary short-term outcome is the
      distribution of time in therapeutic range; the primary long-term outcome
      comprises the composite of stroke, systemic embolism, myocardial infarction,
      major and clinically relevant bleeding, and death. CONCLUSIONS: The thrombEVAL
      project will provide a large prospective observational cohort of patients
      predominantly treated with phenprocoumon. It will evaluate the quality of oral
      anticoagulation in regular medical care and a telemedicine-based coagulation
      service.

PMID- 24685606
TI  - Neurogenin 2 converts mesenchymal stem cells into a neural precursor fate and
      improves functional recovery after experimental stroke.
AB  - BACKGROUND: Neurogenin2 (Ngn2) is a proneural gene that directs neuronal
      differentiation of progenitor cells during development. Here, we investigated
      whether Ngn2 can reprogram MSCs to adopt a neural precursor fate and enhance the
      therapeutic effects of MSCs after experimental stroke. METHODS: In vitro, MSCs
      were transfected with lenti-GFP or lenti-Ngn2. Following neuronal induction,
      cells were identified by immunocytochemistry, Western blot and
      electrophysiological analyses. In a stroke model induced by transient right
      middle cerebral artery occlusion (MCAO), PBS, GFP-MSCs or Ngn2-MSCs were injected
      1 day after MCAO. Behavioral tests, neurological and immunohistochemical
      assessments were performed. RESULTS: In vitro, Ngn2-MSCs expressed neural stem
      cells markers (Pax6 and nestin) and lost the potential to differentiate into
      mesodermal cell types. Following neural induction, Ngn2-MSCs expressed higher
      levels of neuron-specific proteins MAP2, Tuj1 and NeuN, and also expressed
      voltage-gated Na+ channel, which was absent in GFP-MSCs. In vivo, after
      transplantation, Ngn2-MSCs significantly reduced apoptotic cells, decreased
      infarct volume, and increased the expression of VEGF and BDNF. Finally, Ngn2-MSCs
      treated animals showed the highest functional recovery among the three groups.
      CONCLUSIONS: Ngn2 was sufficient to convert MSCs into a neural precursor fate and
      transplantation of Ngn2-MSCs was advantageous for the treatment of stroke rats.

PMID- 24685607
TI  - Diffusion-weighted MR imaging findings of ovarian adenocarcinofibromas and
      adenofibromas.
AB  - We retrospectively evaluated pelvic magnetic resonance imaging including
      diffusion-weighted imaging (DWI) of 16 ovarian lesions (5 adenocarcinofibromas, 2
      borderline adenofibromas, and 9 benign adenofibromas). All adenocarcinofibromas
      were detected as large solid areas of strong high signal on DWI, and seven of
      nine benign adenofibromas and both borderline adenofibromas demonstrated no areas
      of high signal or small areas of weak high signal. Solid components that appear
      as areas of strong high signal on DWI might represent a characteristic finding of
      adenocarcinofibromas. 

PMID- 24685608
TI  - Viral replication kinetics and in vitro cytopathogenicity of parental and
      reassortant strains of bluetongue virus serotype 1, 6 and 8.
AB  - Bluetongue virus (BTV), a segmented dsRNA virus, is the causative agent of
      bluetongue (BT), an economically important viral haemorrhagic disease of
      ruminants. Bluetongue virus can exchange its genome segments in mammalian or
      insect cells that have been co-infected with more than one strain of the virus.
      This process, may potentially give rise to the generation of novel reassortant
      strains that may differ from parental strains in regards to their phenotypic
      characteristics. To investigate the potential effects of reassortment on the
      virus' phenotype, parental as well as reassortant strains of BTV serotype 1, 6,
      8, that were derived from attenuated and wild type strains by reverse genetics,
      were studied in vitro for their virus replication kinetics and cytopathogenicity
      in mammalian (Vero) cell cultures. The results indicate that genetic reassortment
      can affect viral replication kinetics, the cytopathogenicity and extent/mechanism
      of cell death in infected cell cultures. In particular, some reassortants of non
      virulent vaccine (BTV-1 and BTV-6) and virulent field origin (BTV-8) demonstrate
      more pronounced cytopathic effects compared to their parental strains. Some
      reassortant strains in addition replicated to high titres in vitro despite being
      composed of genome segments from slow and fast replicating parental strains. The
      latter result may have implications for the level of viraemia in the mammalian
      host and subsequent uptake and transmission of reassortant strains (and their
      genome segments) by Culicoides vectors. Increased rates of CPE induction could
      further suggest a higher virulence for reassortant strains in vivo. Overall,
      these findings raise questions in regards to the use of modified-live virus (MLV)
      vaccines and risk of reassortment in the field. To further address these
      questions, additional experimental infection studies using insects and/or animal
      models should be conducted, to determine whether these results have significant
      implications in vivo. 

PMID- 24685609
TI  - The changing landscape of allergy immunotherapy in the United States.

PMID- 24685610
TI  - Controlling cell shape changes during salivary gland tube formation in
      Drosophila.
AB  - Any type of tubulogenesis is a process that is highly coordinated between large
      numbers of cells. Like other morphogenetic processes, it is driven to a great
      extent by complex cell shape changes and cell rearrangements. The formation of
      the salivary glands in the fly embryo provides an ideal model system to study
      these changes and rearrangements, because upon specification of the cells that
      are destined to form the tube, there is no further cell division or cell death.
      Thus, morphogenesis of the salivary gland tubes is entirely driven by cell shape
      changes and rearrangements. In this review, we will discuss and distill from the
      literature what is known about the control of cell shape during the early
      invagination process and whilst the tubes extend in the fly embryo at later
      stages. 

PMID- 24685612
TI  - Tissue design: how Drosophila tumors remodel their neighborhood.
AB  - Drosophila genetics has long been appreciated as a powerful approach for
      discovering the normal functions of genes that act as oncogenes and tumor
      suppressors in human cancer. Recent studies have also highlighted its advantages
      for deciphering how such genes function during tumorigenesis itself. Here we
      detail studies relating to how tumors, generated in developing organs and adult
      stem cell-based tissues, remodel the tissue landscape to their benefit. Like
      mammalian tumors, insect tumors can dissolve extracellular matrix, recruit blood
      cells, migrate and invade other tissues. While much is known about how mammalian
      fibroblasts, immune cells and vasculature promote late tumorigenesis, less is
      understood about the very earliest stages of tumor development in mammals.
      Because Drosophila has fewer mitotic cells and a simpler tissue architecture, it
      affords easy detection and analysis of early clonal tumor growth. Drosophila
      studies have revealed both cooperative and competitive interactions between tumor
      and normal cells during early tumor growth. During development, these
      interactions typically occur with other proliferative progenitor cells, but in
      adult stem cell-based tissues, the stem cell niche can fuel tumor growth. 

PMID- 24685613
TI  - Replisome components--post-translational modifications and their effects.
AB  - The process of DNA replication is highly regulated, but at the same time very
      dynamic. Once S-phase is initiated and replication elongation is occurring, the
      cells are committed to complete replication in order to ensure genome stability
      and survival. Many pathways exist to resolve situations where normal replisome
      progression is not possible. It is becoming more and more evident that post
      translational modifications of replisome components play a key role in regulating
      these pathways which ensure fork progression. Here we review the known
      modifications of the progressing replisome and how these modifications are
      thought to affect DNA replication in unperturbed and perturbed S-phases. 

PMID- 24685611
TI  - JAK/STAT pathway dysregulation in tumors: a Drosophila perspective.
AB  - Sustained activation of the JAK/STAT pathway is causal to human cancers. This
      pathway is less complex in Drosophila, and its dysregulation has been linked to
      several tumor models in this organism. Here, we discuss models of metastatic
      epithelial and hematopoietic tumors that are causally linked to dysregulation of
      JAK/STAT signaling in Drosophila. First, we focus on cancer models in imaginal
      discs where ectopic expression of the JAK/STAT pathway ligand Unpaired downstream
      of distinct tumor suppressors has emerged as an unexpected mediator of neoplastic
      transformation. We also discuss the collaboration between STAT and oncogenic Ras
      in epithelial transformation. Second, we examine hematopoietic tumors, where
      mutations that cause hyperactive JAK/STAT signaling are necessary and sufficient
      for "fly leukemia". We highlight the important contributions that genetic screens
      in Drosophila have made to understanding the JAK/STAT pathway, its developmental
      roles, and how its function is co-opted during tumorigenesis. 

PMID- 24685614
TI  - Preface. Trafficking of organelles and proteins in the nervous system.

PMID- 24685615
TI  - WITHDRAWN: Nuclear matrix, nuclear envelope and premature aging syndromes in a
      translational research perspective.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.semcdb.2014.03.022. The duplicate article has
      therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be
      found at http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 24685616
TI  - A historical perspective of pancreatic cancer mouse models.
AB  - Pancreatic cancer is an inherently aggressive disease with an extremely poor
      prognosis and lack of effective treatments. Over the past few decades, much has
      been uncovered regarding the pathogenesis of pancreatic cancer and the underlying
      genetic alterations necessary for tumour initiation and progression. Much of what
      we know about pancreatic cancer has come from mouse models of this disease. This
      review focusses on the development of genetically engineered mouse models that
      phenotypically and genetically recapitulate human pancreatic cancer, as well as
      the increasing use of patient-derived xenografts for preclinical studies and the
      development of personalised medicine strategies. 

PMID- 24685617
TI  - Genetically engineered mouse models for epithelial ovarian cancer: are we there
      yet?
AB  - The development of preclinical spontaneous genetically engineered mouse models
      (GEMMs) requires an understanding of the genetic basis of the human disease. Such
      robust models have proven invaluable for increasing understanding of human
      malignancies as well as identifying new biomarkers and testing new therapies for
      these diseases. While GEMMs have been reported for ovarian cancer, the majority
      have proven disappointing overall in their recapitulation of paired genetic and
      histological features especially for serous ovarian epithelial cancer. This
      review describes GEMMs for ovarian cancer, in particular, high grade serous
      ovarian cancer and assesses these in light of recent changes in our understanding
      of the human malignancy. 

PMID- 24685618
TI  - Regulation of spermatogenesis: an evolutionary biologist's perspective.
AB  - This review describes the regulation of spermatogenesis taking into consideration
      the hypothalamic-pituitary gonadal axis, the male reproductive organs and the
      endocrine and paracrine factors involved in the control of sperm production and
      the release of androgens. Instead of detailed descriptions of many hormones and
      growth factors, we attempt to provide an integrative and evolutionary view by
      comparing different species and considering their specific needs for successful
      male reproduction. The review focuses on species specific differences in the
      structural organization of spermatogenesis and indicates that the crucial
      regulatory mechanisms controlling sperm output are targeted toward
      differentiating spermatogonia when they initiate clonal expansion. We argue that
      the further differentiation of germ cells is following a highly coordinated and
      strictly predetermined morphogenetic cascade widely independent of hormonal
      control. We propose a hypothetical "ancient" model. Spermatogenesis and
      steroidogenesis are controlled by a master switch (GnRH pulse generator) under
      whose control two separate feedback systems provide independent control of
      androgen (LH-testosterone) and sperm production (FSH-inhibin). This scenario
      offers high flexibility and has seen uncountable adaptions to optimize the
      specific needs of different species. Models for the hormonal regulation in
      hamsters, laboratory rodents and primates are presented to illustrate the species
      specific diversity. 

PMID- 24685619
TI  - Predictors of weight loss in obese older adults: findings from the USA and the
      UK.
AB  - OBJECTIVE: To examine the prevalence and demographic predictors of clinically
      meaningful weight loss in community samples of obese older adults in the USA and
      the UK. METHODS: Data were from obese older adults (BMI >= 30 kg/m(2); age >= 52
      years), free of a cancer diagnosis, from the Health and Retirement Study (HRS; n
      = 3398) and the English Longitudinal Study of Ageing (ELSA; n = 998). Weight
      change was assessed from 2004 to 2008. Multivariable logistic regression tested
      whether age, sex, ethnicity, marital status, education, or BMI predicted >= 5%
      weight loss. RESULTS: Over a quarter (28.7%) of obese participants from HRS and
      16.6% from ELSA lost >= 5% weight. Being female (odds ratio (OR) = 1.31, 95%
      confidence interval (CI) = 1.11-1.54) and heavier (BMI >= 35 kg/m(2)) (OR = 1.60,
      95% CI = 1.37-1.87) predicted weight loss in HRS. Trends were similar in ELSA
      (female: OR = 1.18, 95% CI = 0.83-1.69; BMI >= 35 kg/m(2): OR = 1.24, 95% CI =
      0.85-1.82). ORs were increased in >= 65-year-olds in HRS (OR = 1.55, 95% CI =
      1.33-1.81), and reduced in married people in ELSA (OR = 0.69, 95% CI = 0.48
      1.00). Neither education nor ethnicity predicted weight loss in either cohort.
      CONCLUSION: A high proportion of obese older adults experience clinically
      meaningful weight loss, but few demographic variables consistently predict weight
      loss in this population.

PMID- 24685621
TI  - Multiple bio-analytical methods to reveal possible molecular mechanisms of
      developmental toxicity in zebrafish embryos/larvae exposed to tris(2-butoxyethyl)
      phosphate.
AB  - The flame retardant tris(2-butoxyethyl) phosphate (TBEP) is a frequently detected
      contaminant in the environment, wildlife and human milk. The potentially toxic
      effects of TBEP and their underlying molecular mechanisms have not been
      elucidated. Here, zebrafish embryos were exposed to different concentrations of
      TBEP from 4 hours of post-fertilization (hpf) to 120 hpf, and effects on
      embryonic development and global protein expression patterns examined. Our
      results demonstrate that treatment with TBEP (0.8-100mg/L) causes a concentration
      and time-dependent decrease in embryonic survival and the hatching percentage.
      The median lethal concentration was 10.7 mg/L at 120 hpf. Furthermore, exposure
      to 150 or 800 MUg/L TBEP inhibited the degradation and utilization of
      vitellogenins and down-regulated the expression of proteins related to cation
      binding, and lipid transport, uptake and metabolism, accompanied by a decrease in
      heart rate and body length. Exposure to TBEP (150 or 800 MUg/L) also decreased
      the expression of proteins involved in cell proliferation and DNA repair, and led
      to an increased number of apoptotic cells in the tail region. Collectively, our
      results suggest that exposure to TBEP causes toxicity in the developing zebrafish
      by inhibiting the degradation and utilization of nutrients from the mother and
      inducing apoptosis.

PMID- 24685622
TI  - Amount and metal composition of midgut gland metallothionein in shore crabs
      (Carcinus maenas) after exposure to cadmium in the food.
AB  - Accumulation of cadmium in aquatic invertebrates may compromise human food safety
      and anthropogenic additions of cadmium to coastal areas cause concern. Induction
      of crustacean metallothionein has been suggested as a useful biomarker for
      contamination of the aquatic environment with cadmium. We investigated how
      exposure to low concentrations of cadmium in the food affects the subcellular
      binding of cadmium with the shore crab Carcinus maenas as model organism.
      Approximately 80% of the assimilated cadmium was bound in the soluble fraction of
      the midgut gland and of this, 82% was found in the metallothionein fraction.
      Metallothionein synthesis was only induced at the highest exposure level.
      However, the number of cadmium atoms bound per molecule of metallothionein
      increased linearly with exposure, from approximately 0.18 in the control group to
      1.4 in a group administered food containing 5.1 MUg Cd g(-1). We noted a marked
      interaction between the presence of copper and zinc in the midgut gland and the
      binding of cadmium. The usefulness of crustacean midgut gland metallothionein as
      a biomarker for cadmium exposure at modest levels was questioned since exposures
      at levels producing significant increases in the tissue contents of the metal did
      not result in elevated concentrations of metallothionein in the midgut gland.

PMID- 24685620
TI  - Metabolic tinkering by the gut microbiome: Implications for brain development and
      function.
AB  - Brain development is an energy demanding process that relies heavily upon diet
      derived nutrients. Gut microbiota enhance the host's ability to extract otherwise
      inaccessible energy from the diet via fermentation of complex oligosaccharides in
      the colon. This nutrient yield is estimated to contribute up to 10% of the host's
      daily caloric requirement in humans and fluctuates in response to environmental
      variations. Research over the past decade has demonstrated a surprising role for
      the gut microbiome in normal brain development and function. In this review we
      postulate that perturbations in the gut microbial-derived nutrient supply, driven
      by environmental variation, profoundly impacts upon normal brain development and
      function. 

PMID- 24685623
TI  - Transgenic fluorescent zebrafish Tg(fli1:EGFP)y1 for the identification of
      vasotoxicity within the zFET.
AB  - The fish embryo toxicity test (FET) is currently one of the most advocated animal
      alternative tests in ecotoxicology. To date, the application of the FET with
      zebrafish (zFET) has focused on acute toxicity assessment, where only lethal
      morphological effects are accounted for. An application of the zFET beyond acute
      toxicity, however, necessitates the establishment of more refined and
      quantifiable toxicological endpoints. A valuable tool in this context is the use
      of gene expression-dependent fluorescent markers that can even be measured in
      vivo. We investigated the application of embryos of Tg(fli1:EGFP)(y1) for the
      identification of vasotoxic substances within the zFET. Tg(fli1:EGFP)(y1) fish
      express enhanced GFP in the entire vasculature under the control of the fli1
      promoter, and thus enable the visualization of vascular defects in live zebrafish
      embryos. We assessed the fli1 driven EGFP-expression in the intersegmental blood
      vessels (ISVs) qualitatively and quantitatively, and found an exposure
      concentration related increase in vascular damage for chemicals like triclosan,
      cartap and genistein. The fluorescence endpoint ISV-length allowed an earlier and
      more sensitive detection of vasotoxins than the bright field assessment method.
      In combination with the standard bright field morphological effect assessment, an
      increase in significance and value of the zFET for a mechanism-specific toxicity
      evaluation was achieved. This study highlights the benefits of using transgenic
      zebrafish as convenient tools for identifying toxicity in vivo and to increase
      sensitivity and specificity of the zFET.

PMID- 24685624
TI  - Regional cortical thinning and cerebrospinal biomarkers predict worsening daily
      functioning across the Alzheimer's disease spectrum.
AB  - BACKGROUND: Impairment in instrumental activities of daily living (IADL) heralds
      the transition from mild cognitive impairment (MCI) to dementia and is a major
      source of burden for both the patient and caregiver. OBJECTIVE: To investigate
      the relationship between IADL and regional cortical thinning and cerebrospinal
      fluid (CSF) Alzheimer's disease (AD) biomarkers cross-sectionally and
      longitudinally in clinically normal (CN) elderly, MCI, and mild AD dementia
      subjects. METHODS: Two hundred and twenty nine CN, 395 MCI, and 188 AD dementia
      subjects participating in the Alzheimer's Disease Neuroimaging Initiative
      underwent baseline magnetic resonance imaging, baseline lumbar puncture, and
      clinical assessments, including the Functional Activities Questionnaire used to
      measure IADL, every 6 to 12 months up to 3 years. General linear regression and
      mixed effects models were employed. RESULTS: IADL impairment was associated with
      the interactions between lower inferior temporal cortical thickness and diagnosis
      (p < 0.0001), greater lateral occipital cortical thickness and diagnosis (p <
      0.0001), and greater amyloid-beta 1-42 (Abeta1-42) and diagnosis (p = 0.0002) at
      baseline (driven by AD dementia). Lower baseline supramarginal (p = 0.02) and
      inferior temporal (p = 0.05) cortical thickness, lower Abeta1-42 (p < 0.0001),
      and greater total tau (t-tau) (p = 0.02) were associated with greater rate of
      IADL impairment over time. CONCLUSIONS: Temporal atrophy is associated with IADL
      impairment in mild AD dementia at baseline, while baseline parietal and temporal
      atrophy, lower CSF Abeta1-42, and greater t-tau predict worsening IADL impairment
      over time across the AD spectrum. These results emphasize the importance of
      assessing IADL at the stage of MCI and even at the transition from CN to MCI.

PMID- 24685625
TI  - Celastrol enhances cell viability and inhibits amyloid-beta production induced by
      lipopolysaccharide in vitro.
AB  - BACKGROUND: Neuroinflammation is a notable hallmark of Alzheimer's disease
      pathogenesis and can markedly exacerbate amyloid pathology. Celastrol, a
      pentacyclic-triterpene, has been found to possess anti-inflammatory properties.
      OBJECTIVE: The purpose of this study was to characterize the effects of celastrol
      on cell viability and amyloid-beta (Abeta) peptide production induced by
      lipopolysaccharide (LPS) administration in H4 human neuroglioma cells stably
      transfected to overexpress human full length APP (H4-APP). METHODS: H4-APP cells
      were exposed to 1, 10, and 100 nM of celastrol in the presence of 0.1 MUg/ml or
      100 MUg/ml of LPS for 24 hours. The effects of celastrol were determined using
      MTT cell viability assay, immunohistochemistry, western blot, and ELISA. RESULTS:
      Cell viability tests revealed that a dose-dependent death of H4-APP cells
      following administration of LPS. Moreover, celastrol significantly reduced (p <
      0.05) cell death induced by LPS compared to LPS alone. Furthermore, the
      administration of celastrol was associated with a significant reduction in LPS
      stimulated Abeta production compared to LPS alone. Western blot and
      immunofluorescence analysis showed that exposure to celastrol increased HSP-70
      and Bcl-2 expression but decreased NFkappaB activity, phosphorylated glycogen
      synthase kinase-3beta (GSK-3beta) at tyrosine 216 and cyclooxygenase-2 (COX-2)
      expression, Abeta accumulation together with a reduction of superoxide and
      hydrogen peroxide generation. HSP-70 siRNA abolished celastrol mediated
      cytoprotection. CONCLUSION: This study demonstrates that celastrol reduced both
      LPS-induced cell death and Abeta production in vitro through increasing HSP-70
      and Bcl-2 expression and reducing NFkappaB, COX-2, and GSK-3beta expression and
      oxidative stress.

PMID- 24685626
TI  - Neuroanatomical correlates of emotional blunting in behavioral variant
      frontotemporal dementia and early-onset Alzheimer's disease.
AB  - BACKGROUND: Emotional blunting is a characteristic feature of behavioral variant
      frontotemporal dementia (bvFTD) and can help discriminate between patients with
      bvFTD and other forms of younger-onset dementia. OBJECTIVE: We compared the
      presence of emotional blunting symptoms in patients with bvFTD and early-onset
      Alzheimer's disease (AD), and investigated the neuroanatomical associations
      between emotional blunting and regional brain volume. METHODS: Twenty-five
      individuals with bvFTD (n = 11) and early-onset AD (n = 14) underwent magnetic
      resonance imaging (MRI) and were rated on symptoms of emotional blunting using
      the Scale for Emotional Blunting (SEB). The two groups were compared on SEB
      ratings and MRI-derived brain volume using tensor-based morphometry. Voxel-wise
      linear regression was performed to determine neuroanatomical correlates of SEB
      scores. RESULTS: The bvFTD group had significantly higher SEB scores compared to
      the AD group. On MRI, bvFTD patients had smaller bilateral frontal lobe volume
      compared to AD patients, while AD patients had smaller bilateral temporal and
      left parietal volume than bvFTD patients. In bvFTD, SEB ratings were strongly
      correlated with right anterior temporal volume, while the association between SEB
      and the right orbitofrontal cortex was non-significant. CONCLUSIONS: Symptoms of
      emotional blunting were more prevalent in bvFTD than early-onset AD patients.
      These symptoms were particularly associated with right-sided atrophy, with
      significant involvement of the right anterior temporal region. Based on these
      findings, the SEB appears to measure symptoms of emotional blunting that are
      localized to the right anterior temporal lobe.

PMID- 24685627
TI  - The role of neurosonology in the diagnosis of vascular dementia.
AB  - Although transcranial sonography is not yet an established diagnostic modality
      for dementia screening or differential diagnosis of Alzheimer's disease (AD) from
      vascular dementia (VaD), intracranial hemodynamic assessment may provide crucial
      information about the association between cognitive deterioration and vascular
      risk factors. We conducted a systematic narrative review of available literature
      through MEDLINE and EMBASE search to identify all available data about the
      evaluation of VaD patients with transcranial Doppler, and to discuss further the
      vascular disorders of the cerebral circulation in patients with vascular
      cognitive impairment. According to the available literature data to date, VaD
      patients were found to have lower mean flow velocity values in four studies
      (indicating cerebral hypoperfusion), higher pulsatility indices in three studies
      (indicating increased downstream vascular resistance), and more severe impairment
      of cerebrovascular reactivity in five studies (indicating exhausted vasodilatory
      reserve) compared to AD patients and controls. Microembolic signals were also
      found to be significantly more common in patients with VaD or AD compared to
      their age- and gender-matched controls, suggesting that asymptomatic
      microembolism, apart for being only marker of VaD, could presumably be involved
      in the genesis of dementia, and in the overlap between VaD and AD. Further
      studies with larger and carefully selected groups are required to eliminate
      potential confounders and to set specific cut-off values for the aforementioned
      hemodynamic parameters in demented patients and dementia subtypes. 

PMID- 24685628
TI  - Has prenatal folate supplementation established an at-risk population for age
      related cognitive decline?
AB  - Nutrition exerts a pervasive impact on normal and pathological conditions of the
      nervous system throughout life. Maternal folate supplementation during pregnancy
      has reduced developmental disorders of the nervous system, but may have also
      fostered an increase in individuals harboring genetic polymorphisms that
      compromise folate usage. Such individuals may harbor a lifetime requirement for
      additional dietary folate, often not met beyond peri/postnatal periods. An
      increased association of such polymorphisms has been detected in individuals with
      autism. Prenatal nutritional supplementation may have inadvertently established
      latent conditions that, in the absence of continued supplementation, may lead to
      age-related cognitive decline. 

PMID- 24685630
TI  - Effects of cognitive training on gray matter volumes in memory clinic patients
      with subjective memory impairment.
AB  - Subjective memory impairment (SMI) is a common risk factor for Alzheimer's
      disease, with few established options for treatment. Here we investigate the
      effects of two months episodic memory training on regional brain atrophy in 19
      memory clinic patients with SMI. We used a sensitive longitudinal magnetic
      resonance imaging protocol and compared the patients with 42 matched healthy
      volunteers randomly assigned to a group performing the same training, or a no
      training control group. Following intervention, the SMI sample exhibited
      structural gray matter volume increases in brain regions encompassing the
      episodic memory network, with cortical volume expansion of comparable extent as
      healthy training participants. Further, we found significant hippocampal volume
      increases in the healthy training group but not in the SMI group. Still,
      individual differences in left hippocampal volume change in the patient group
      were related to verbal recall improvement following training. The present results
      reinforce earlier studies indicating intact brain plasticity in aging, and
      further suggest that training-related brain changes can be evident also in the
      earliest form of cognitive impairment. 

PMID- 24685629
TI  - Increased hippocampal blood flow in sedentary older adults at genetic risk for
      Alzheimer's disease.
AB  - Resting cerebral blood flow (CBF) decreases with age; however regulatory
      increases in hippocampal CBF have been associated with genetic risk
      (Apolipoprotein E [APOE] epsilon4 carriers) for Alzheimer's disease (AD).
      Although physical activity exerts beneficial effects on CBF in healthy elderly,
      the effects of sedentary behaviors on CBF remain unknown. We measured resting
      hippocampal CBF (via arterial spin labeling magnetic resonance imaging) and
      sedentary time/physical activity (via accelerometry) on 33 cognitively healthy
      adults (ages 52-81), 9 of which were APOE epsilon4 carriers. Results indicate
      that the relationship between sedentary time and CBF in the left hippocampus
      differs by APOE status, whereby APOE epsilon4 carriers show higher CBF as a
      function of longer sedentary time (B = 10.8, SE = 3.17, beta = 0.74, t = 3.41, p
      < 0.01) compared to noncarriers (B = 1.4, SE = 2.7, beta = 0.096, t = 0.51, p =
      0.61), possibly suggesting a CBF regulatory response to compensate for metabolic
      alterations in dementia risk. These preliminary data suggest that the
      relationship between CBF and sedentary time is different in APOE epsilon4
      carriers and noncarriers and that sedentary time may act as a behavioral risk
      factor for CBF dysregulation in those at genetic risk for developing AD. More
      research is needed to further understand the role of sedentary behaviors and
      physical activity on CBF, especially in individuals at genetic risk of developing
      AD. 

PMID- 24685632
TI  - Cognitive, genetic, and brain perfusion factors associated with four year
      incidence of Alzheimer's disease from mild cognitive impairment.
AB  - BACKGROUND: There is a range of factors that predict the development of
      Alzheimer's disease (AD) dementia among patients with amnestic mild cognitive
      impairment (MCI). OBJECTIVES: To identify the neuropsychological, genetic, and
      functional brain imaging data that best predict conversion to AD dementia in
      patients with amnestic MCI. METHODS: From an initial group of 42 amnestic MCI
      patients assessed with neurological, neuropsychological, and brain SPECT, 39 (25
      converters, 14 non-converters) were followed for 4 years, and 36 had APOE
      epsilon4 genotyping. Baseline neuropsychological data and brain SPECT data were
      used to predict which of the MCI patients would develop dementia by the end of
      the 4 years of observation. RESULTS: The MCI patients who had converted to AD
      dementia had poorer performance on long-term visual memory and Semantic Fluency
      tests. The MCI subjects who developed dementia were more likely to carry at least
      one copy of the APOE epsilon4 allele (Hazard Risk = 4.22). There was lower brain
      perfusion in converters than non-converters, mainly in postcentral gyrus. An
      additional analysis of the SPECT data found differences between the MCI subjects
      and controls in the posterior cingulate gyrus and the basal forebrain. When the
      brain imaging and neuropsychological test data were combined in the same Cox
      regression model, only the neuropsychological test data were significantly
      associated with time to dementia. CONCLUSION: Although the presence of reduced
      brain perfusion in postcentral gyrus and basal forebrain indicated an at-risk
      condition, it was the extent of memory impairment that was linked to the speed of
      decline from MCI to AD.

PMID- 24685633
TI  - Age-dependent increment of hydroxymethylation in the brain cortex in the triple
      transgenic mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex disorder whose etiology is associated with
      environmental and genetic factors. Recently there have been several attempts to
      analyze the role of epigenetic alterations in the origin and progression of this
      neurodegenerative condition. To evaluate the potential participation of the
      methylation status of the genome that may contribute to AD progression, we have
      studied the levels and distribution of the 5-methylcytosine and 5
      hydroxymethylcytosine in different brain regions at different ages. We analyzed
      and quantified the immunosignal of these two epigenetic marks in young versus old
      wild-type mice and in the triple-transgenic mouse model of AD (3xTg-AD). The
      results show a decline in global 5-methylcytosine mark over time in all studied
      brain regions concomitant with a significant and widespread increase in 5
      hydroxymethylcytosine mark in the aged transgenic mice in contrast to the age
      matched controls. These differences in the methylation pattern of brain DNA in
      the 3xTg-AD that accumulates along age indicates abnormal formation of permissive
      chromatin structure associated with the increase in AD-related markers. 

PMID- 24685634
TI  - Apolipoprotein C-III is an amyloid-beta-binding protein and an early marker for
      Alzheimer's disease.
AB  - It has been demonstrated that peripheral injection of anti-amyloid-beta (Abeta)
      antibodies to patients with Alzheimer's disease (AD) and AD transgenic mice
      facilitate Abeta clearance. We hypothesized that peripheral circulating Abeta
      binding proteins also possess the ability to enhance Abeta clearance and the
      levels of circulating Abeta-binding proteins could serve as early AD biomarkers.
      Circulating Abeta-binding proteins were isolated from plasma and identified by LC
      MS/MS. Their levels were compared among non-demented individuals without AD
      family history (ND), with AD family history (ND-FH), and patients with mild AD.
      The results showed that most of the identified Abeta-binding proteins were
      apolipoproteins, i.e., apoA-I, apoB-100, apoC-III, and apoE. Abeta bound
      preferentially to apoA-I-enriched HDL, followed by apoC-III- and apoE-enriched
      VLDL, and bound less favorably to apoB-100-enriched LDL. Levels of apoA-I were
      reduced in AD patients and could be used to discriminate AD from ND groups (AUC:
      0.93); whereas levels of apoC-III were reduced in both ND-FH and AD groups and
      could be used to differentiate ND-FH from ND individuals (AUC: 0.81). Both the
      levels of apoA-1 and apoC-III positively correlated with CASI and MMSE scores. In
      conclusion, these results suggest that plasma apoA-I could be a sensitive AD
      biomarker and individuals with low plasma levels of apoC-III are at risk for AD. 

PMID- 24685636
TI  - Tissue transglutaminase in Alzheimer's disease: involvement in pathogenesis and
      its potential as a therapeutic target.
AB  - Protein misfolding and the formation of stable insoluble protein complexes by
      self-interacting proteins, in particular amyloid-beta and tau protein, play a
      central role in the pathogenesis of Alzheimer's disease (AD). Unfortunately, the
      underlying mechanisms that trigger the misfolding of self-interacting proteins
      that eventually results in formation of neurotoxic dimers, oligomers, and
      aggregates remain unclear. Elucidation of the driving forces of protein complex
      formation in AD is of crucial importance for the development of disease-modifying
      therapies. Tissue transglutaminase (tTG) is a calcium-dependent enzyme that
      induces the formation of covalent epsilon-(gamma-glutamyl)lysine isopeptide
      bonds, which results in both intra- and intermolecular protein cross-links. These
      tTG-catalyzed intermolecular cross-links induce stable, rigid, and insoluble
      protein complexes, whereas intramolecular cross-links change the conformation of
      proteins. Inhibition of tTG-catalyzed cross-linking counteracts the formation of
      protein aggregates, as observed in disease-models of other protein misfolding
      diseases, in particular Parkinson's and Huntington's diseases. Although data of
      tTG activity in AD models is limited, there is compelling evidence from both in
      vitro and postmortem human brain tissue of AD patients that point toward a
      crucial role for tTG in the pathogenesis of AD. Here, we review these data on the
      role of tTG in the initiation and development of protein aggregates in AD, and
      discuss the possibility to use inhibitors of the cross-linking activity of tTG as
      a new therapeutic approach for AD. 

PMID- 24685637
TI  - Brain region-specific monoaminergic correlates of neuropsychiatric symptoms in
      Alzheimer's disease.
AB  - Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are present during
      the disease course of nearly all AD patients and consist of psychosis,
      agitation/aggression, and depression, among others. Given their detrimental
      consequences regarding life expectancy, cognition, and socio-economic costs, it
      is essential to elucidate their neurochemical etiology to facilitate the
      development of novel and effective pharmacotherapeutics. This study attempted to
      identify brain region-specific monoaminergic correlates of NPS by measuring the
      levels of eight monoamines and metabolites in nine relevant postmortem brain
      regions of 40 behaviorally characterized AD patients, i.e., dopamine (DA),
      serotonin (5-HT), (nor)epinephrine and their respective metabolites 3,4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid, 5-hydroxy-3
      indoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), using RP
      HPLC-ECD. Likewise, Mini-Mental State Examination (MMSE) score correlates of
      monoaminergic neurotransmitter alterations were calculated. As a result, MMSE
      scores, used as a measure of dementia severity, correlated positively with
      hippocampal 5-HIAA levels as well as with 5-HT levels of the superior temporal
      gyrus and cerebellar cortex. Furthermore, hippocampal 5-HIAA levels inversely
      correlated with agitation scores, whereas thalamic MHPG levels comparably did
      with the presence of hallucinations. Finally, in the cerebellar cortex, DOPAC/DA
      ratios, indicative of DA turnover, correlated with physically agitated behavior
      while MHPG levels correlated with affective disturbances. These findings support
      the assumption that specific NPS features in AD might be (in)directly related to
      brain region-specific monoaminergic neurotransmitter alterations. Additionally,
      the effect of AD pathology on neurochemical alterations in the cerebellum
      requires further examination due to its important but underestimated role in the
      neurochemical pathophysiology of NPS in AD. 

PMID- 24685635
TI  - Increased plasma TACE activity in subjects with mild cognitive impairment and
      patients with Alzheimer's disease.
AB  - Evidence suggests that the tumor necrosis factor receptor (TNFR)-signaling
      pathway contributes to the pathogenesis of Alzheimer's disease (AD). TNF-alpha
      converting enzyme (TACE/ADAM-17) can cleave both pro-TNF-alpha and TNF receptors.
      Recently, we have shown that TACE activity in the cerebrospinal fluid (CSF) of
      subjects with mild cognitive impairment (MCI) and AD patients is significantly
      higher than that of cognitively healthy controls (HC). To date, it is not clear
      whether TACE activity could be detected in the human plasma and whether TACE
      activity in MCI and AD patients is different from that in HC. We analyzed TACE
      expression and activity in a large clinical sample of 64 patients with AD, 88
      subjects with MCI, and 50 age-matched HC recruited from two distinct academic
      centers. Plasma TACE protein levels did not differ significantly in the three
      study groups (AD, MCI, and HC). However, plasma TACE activity in subjects with
      MCI and AD patients was significantly higher than that in HC. Moreover, in MCI
      and AD groups, we found a significant correlation between plasma TACE activity
      and CSF t-tau and Abeta42 levels and CSF Abeta42/tau ratios. In AD patients, the
      levels of plasma TACE activity correlated significantly and negatively with
      cognition. These findings further support the role of the TNF-alpha receptor
      complex in AD-related neuroinflammation and propose TACE plasma activity as a
      promising hypothesis-driven biomarker candidate for detection, diagnosis, and
      prognosis of prodromal and clinical AD. 

PMID- 24685639
TI  - N-terminal 5-mer peptide analog P165 of amyloid precursor protein inhibits UVA
      induced MMP-1 expression by suppressing the MAPK pathway in human dermal
      fibroblasts.
AB  - Exposure to ultraviolet (UV) radiation leads to a progressive increase in dermal
      damage through the degradation of collagen, which is mediated by matrix
      metalloproteinases (MMPs). UV radiation alters the intracellular signaling events
      that regulate the elaboration of MMPs. Our previous study showed that P165, the N
      terminal 5-mer peptide analog of amyloid precursor protein, exerts a protective
      effect on ultraviolet A (UVA)-induced loss of collagen type I in human dermal
      fibroblasts (HDFs) by inhibiting the generation of intracellular reactive oxygen
      species and MMP-1. In this study, we focused on specific signal transduction
      pathways to elucidate the possible photoprotective mechanisms of P165 in
      controlling MMP-1 inhibition. Results from western blot analyses indicated that
      pretreatment with P165 dose-dependently inhibited UVA-induced phosphorylation of
      extracellular regulated protein kinases (ERK), c-Jun N-terminal kniase (JNK), p38
      mitogen-activated protein kinases (MAPKs), and the phosphorylation of their
      downstream targets c-Jun and c-Fos. The photoprotective effects of P165 were
      further demonstrated in collagen type I secretion and cellular senescence induced
      by UVA irradiation. These findings suggest that P165 exerts photoprotective
      activity in UVA-treated HDFs by regulating MMP-1 generation. This activity may be
      mediated by inhibiting the MAPK signaling pathways. Thus, P165 is a potential
      agent for the prevention of skin photoaging. 

PMID- 24685638
TI  - Dopamine D(3) receptors contribute to methamphetamine-induced alterations in
      dopaminergic neuronal function: role of hyperthermia.
AB  - Methamphetamine administration causes long-term deficits to dopaminergic systems
      that, in humans, are thought to be associated with motor slowing and memory
      impairment. Methamphetamine interacts with the dopamine transporter (DAT) and
      increases extracellular concentrations of dopamine that, in turn, binds to a
      number of dopamine receptor subtypes. Although the relative contribution of each
      receptor subtype to the effects of methamphetamine is not fully known, non
      selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine
      induced changes to dopamine systems. The present study extended these findings by
      testing the role of the dopamine D3 receptor subtype in mediating the long-term
      dopaminergic, and for comparison serotonergic, deficits caused by
      methamphetamine. Results indicate that the dopamine D3 receptor selective
      antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal
      DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as
      assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine
      induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by
      treating rats in a warm ambient environment, PG01037 failed to attenuate the
      effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate
      methamphetamine-induced decreases in dopamine and 5HT content. Taken together,
      the present study demonstrates that dopamine D3 receptors mediate, in part, the
      long-term deficits in DAT function caused by methamphetamine, and that this
      effect likely involves an attenuation of methamphetamine-induced hyperthermia. 

PMID- 24685640
TI  - The effect of acute simvastatin administration on the severity of arrhythmias
      resulting from ischaemia and reperfusion in the canine: Is there a role for
      nitric oxide?
AB  - The present study has examined the effects and the possible mechanisms of a
      single dose of simvastatin on the severity of arrhythmias resulting from a 25min
      occlusion and reperfusion of the left anterior descending coronary artery in
      anaesthetized (chloralose and urethane) dogs. The control animals (n=16) were
      given the solvent of simvastatin by slow (over 5min) intracoronary (ic.)
      injection just prior to the occlusion. Twenty-six dogs were treated with
      simvastatin (0.1mg/kg) by the same route, both in the absence (n=15) and in the
      presence (n=11) of l-NAME. This latter was administered (5mg/kg, ic.) either
      alone (n=12) or 10min before the simvastatin treatment. The severity of ischaemia
      (epicardial ST-segment, inhomogeneity) and ventricular arrhythmias (ventricular
      premature beats [VPBs], ventricular tachycardia [VT] and fibrillation [VF]),
      plasma nitrite/nitrate levels, myocardial superoxide production and eNOS activity
      were assessed. Compared with controls simvastatin significantly reduced the
      number of VPBs (289+/-34vs. 94+/-25) and the episodes of VT (5.6+/-1.3vs. 0.3+/
      0.2), the incidence of VT (88% vs. 20%) and VF (56% vs. 0%) during occlusion and
      increased survival (0% vs. 33%) on reperfusion. There were also less marked
      ischaemic changes in the simvastatin-treated dogs than in the controls.
      Simvastatin preserved eNOS activity and nitric oxide (NO) bioavailability during
      occlusion and attenuated superoxide production following reperfusion. All these
      effects of simvastatin (except for the protection against VF) were reversed by l
      NAME. We conclude that simvastatin given just prior to ischaemia/reperfusion
      reduces the severity of arrhythmias. This effect involves both NO-dependent and
      NO-independent mechanisms. 

PMID- 24685641
TI  - Greater organ involution in highly proliferative tissues associated with the
      early onset and acceleration of ageing in humans.
AB  - Domination of cell proliferation over cell death is a driving force for
      carcinogenesis, whereas reduced cell proliferation and increased cell death are
      characteristic of ageing. We employed published data to estimate representative
      mean values of cell turnover times for 31 different organs and tissues in adult
      humans and animals (when data in humans were lacking) as well as functional mass
      loss for 5 organs, accounting for actual mass loss and tissue conversion to fat,
      in humans over the adult period, age 25 to 70. We found that greater actual and
      functional mass loss was significantly associated (P=0.001 and P<0.0001,
      respectively) with the log of shorter cell turnover times. We propose that this
      is characteristic of stem cell exhaustion and replicative senescence. In
      addition, we provide quantitative evidence that, in many organs, involution is
      evident even in young adults. On the basis of published mass measurements of
      major organs, by analysis of covariance, we identified examples of significant
      (P<=0.05), accelerated actual or functional mass loss and ageing from early to
      late adulthood. We hypothesise and quantitatively demonstrate that functional
      mass loss accelerates with ageing by incorporating the contribution of actual
      mass loss, tissue conversion to fatty or fibrous tissue, and the presence of
      apoptotic, necrotic and senescent cells. We propose that mass loss, linked to
      replicative senescence, is an evolutionary adaptation that effectively limits
      cancer in young adults, as mass loss is first apparent soon after the end of the
      growth period, accelerating in the more elderly as biological conditions deviate
      away from those prevailing in youth, when the selective pressure on pleiotropic
      genes is greatest. 

PMID- 24685642
TI  - Complete genome sequence of Lactobacillus reuteri I5007, a probiotic strain
      isolated from healthy piglet.
AB  - Lactobacillus reuteri I5007 is a well-characterized probiotic strain isolated
      from the colonic mucosa of healthy weaning piglets. Here, we present the complete
      genome sequence of this strain, which consists of a circular chromosome and six
      distinct plasmids. 

PMID- 24685643
TI  - [Breastfeeding after breast surgery: patient information].
AB  - OBJECTIVES: Partial mastectomy, augmentation and reduction mammaplasty are often
      operated on women who are not yet bothered by breastfeeding. The objectives of
      this study were to evaluate the information given to patients before surgery, and
      describe difficulties that mothers confront when starting breastfeeding in order
      to create a reference document about breastfeeding to inform patients who will
      undergo such surgery in the future. MATERIAL AND METHODS: We led one first study
      to evaluate the surgeons' practice in the Reunion Island and a second
      retrospective and descriptive study upon patients. RESULTS: We encountered the
      fact that few patients in childbearing age ask for information about
      breastfeeding before undergoing surgery, but surgeons do not systematically give
      such information either, even less before partial mastectomy. The impact of
      surgery on breastfeeding depends on the type of intervention and the surgical
      technique. Even though breastfeeding is possible, the mean period of
      breastfeeding after surgery is shorter and the most frequent difficulty
      encountered is lactation insufficiency, even more after reduction mammaplasty,
      periareolar incision, and nipple hypoesthesia after surgery. DISCUSSION AND
      CONCLUSION: The information document that we tried to establish concerning
      breastfeeding after partial mastectomy, augmentation and reduction mammaplasty,
      may compensate patients' lack of information and sums up all the complications
      described in our study and in the literature.

PMID- 24685644
TI  - [E.G. Simon, C.J. Arthuis, F. Perrotin in reply to the article by T. Boisrame et
      al].

PMID- 24685645
TI  - [Prenatal three-vessel and tracheal view: abnormal features].
AB  - Good knowledge of normal characteristics of prenatal three vessels and trachea
      view allows not only to detect, but also to identify abnormalities such as normal
      variants and malformations of interest to main vessels (trunk of the pulmonary
      artery and its branches, the aorta and the superior vena cava) and various
      vascular structures in the anterior-superior mediastinum. These abnormalities may
      be isolated or associated with other anomalies of cardiac architecture. 

PMID- 24685646
TI  - Targeted therapies in urothelial carcinoma.
AB  - PURPOSE OF REVIEW: Greater understanding of the biology and genetics of
      urothelial carcinoma is helping to identify and define the role of molecules and
      pathways appropriate for novel-targeted therapies. Here, we review the targeted
      therapies that have been reported or are in ongoing urothelial carcinoma clinical
      trials, and highlight molecular targets characterized in preclinical and clinical
      studies. RECENT FINDINGS: Trials in nonmuscle-invasive bladder cancer are
      evaluating the role of immunotherapy and agents targeting vascular endothelial
      growth factor (VEGF) or fibroblast growth factor receptor-3. In muscle-invasive
      bladder cancer, neoadjuvant studies have focused on combining VEGF agents with
      chemotherapy; adjuvant studies are testing vaccines and agents targeting the
      human epidermal growth factor receptor 2, p53, and Hsp27. In the first-line
      treatment of metastatic urothelial carcinoma, tubulin, cytotoxic T-lymphocyte
      antigen 4, Hsp27, and p53 are novel targets in clinical trials. The majority of
      targeted agents studied in urothelial carcinoma are in the second-line setting;
      new targets include CD105, polo-like kinase-1, phosphatidylinositide 3-kinases
      (PI3K), transforming growth factor beta receptor/activin receptor-like kinase
      beta, estrogen receptor, and the hepatocyte growth factor receptor (HGFR or MET).
      SUMMARY: Development of targeted therapies for urothelial carcinoma is still in
      early stages, consequently there have been no major therapeutic advances to date.
      However, greater understanding of urothelial carcinoma and solid tumor biology
      has resulted in a proliferation of clinical trials that could lead to significant
      advances in treatment strategies.

PMID- 24685647
TI  - Comparative proteomic analysis of anti-cancer mechanism by periplocin treatment
      in lung cancer cells.
AB  - BACKGROUND: Periplocin is used for treatment of rheumatoid arthritis,
      reinforcement of bones and tendons, palpitations or shortness of breath and lower
      extremity edema in traditional medicine. Our previous findings suggested that
      periplocin could inhibit the growth of lung cancer both in vitro and in vivo. But
      the biological processes and molecular pathways by which periplocin induces these
      beneficial effects remain largely undefined. METHODS: To explore the molecular
      mechanisms of periplocin involved in anti-cancer activity, in the present study
      the protein profile changes of human lung cancer cell lines A549 in response to
      periplocin treatment were investigated using the proteomics approaches (2-DE
      combined with MS/MS). Western blot was employed to verify the changed proteins.
      Interactions between changed proteins were analyzed by STRING. RESULTS: 29 down
      regulated protein species named GTP-binding nuclear protein Ran (RAN), Rho GDP
      dissociation inhibitor 1 (ARHGDIA), eukaryotic translation initiation factor 5A-1
      (EIF5A) and Profilin-1(PFN1), and 10 up-regulated protein species named Heat
      shock cognate 71 kDa protein (HSPA8),10 kDa heat shock protein (HSPE1), and
      Cofilin-1(CFL-1) were identified. Among them, GTP-binding nuclear protein Ran
      (RAN) and Rho GDP-dissociation inhibitor 1 (ARHGDIA) were the most significantly
      changed (over tenfold). The proteasome subunit beta type-6 (PSMB6), ATP synthase
      ecto-alpha-subunit (ATP5A1), Aldehyde dehydrogenase 1 (ALDH1) and EIF5A were
      verified by immunoblot assays to be dramatically down-regulated. By STRING
      bioinformatics analysis revealing interactions and signaling networks it became
      apparent that the proteins changed they are primarily involved in transcription
      and proteolysis. CONCLUSION: Periplocin inhibited growth of lung cancer by down
      regulating proteins, such as ATP5A1, EIF5A, ALDH1 and PSMB6. These findings may
      improve our understanding of the molecular mechanisms underlying the anti-cancer
      effects of periplocin on lung cancer cells.

PMID- 24685648
TI  - An integrative review of dignity in end-of-life care.
AB  - BACKGROUND: Dying with dignity is regarded as a goal of quality end-of-life care.
      However, the meaning of dying with dignity is ambiguous, and no comprehensive
      synthesis of the existing literature has been published. AIM: To synthesize the
      meaning of dying with dignity and to identify common aspects of dignity in end-of
      life care. DESIGN: This is an integrative review article. Methodological
      strategies specific to the integrative review method proposed by Whittemore and
      Knafl were followed to conduct data analysis. The matrix method was used to
      summarize characteristics of included articles. DATA SOURCES: Five electronic
      databases were searched in October 2012, with no date restriction: PubMed,
      CINAHL, PsycINFO, Academic Search Premier, and Social Sciences Abstracts.
      Theoretical reports, and both qualitative and quantitative empirical reports,
      focused on dignity in end-of-life care were included. RESULTS: Themes of dying
      with dignity are as follows: a human right, autonomy and independence, relieved
      symptom distress, respect, being human and being self, meaningful relationships,
      dignified treatment and care, existential satisfaction, privacy, and calm
      environment. Factors influencing dignity include demographic, illness-related,
      and treatment-/care-related factors, as well as communication. Models of dignity
      in end-of-life care and instruments to measure dignity were reported.
      Interventions to support dignity stressed physical, psychological, and spiritual
      supports not only to dying patients but also to family members. CONCLUSION: This
      review clarified the meaning of dying with dignity and synthesized common aspects
      of dignity in end-of-life care. Further research is needed to evaluate the
      meaning of dying with dignity across cultures and to explore individualized
      dignity-based care.

PMID- 24685649
TI  - Impact of a novel online learning module on specialist palliative care nurses'
      pain assessment competencies and patients' reports of pain: Results from a quasi
      experimental pilot study.
AB  - BACKGROUND: Pain is a complex multidimensional phenomenon moderated by consumer,
      provider and health system factors. Effective pain management cuts across
      professional boundaries, with failure to screen and assess contributing to the
      burden of unrelieved pain. AIM: To test the impact of an online pain assessment
      learning module on specialist palliative care nurses' pain assessment
      competencies, and to determine whether this education impacted positively on
      palliative care patients' reported pain ratings. DESIGN: A quasi-experimental
      pain assessment education pilot study utilising 'Qstream(c)', an online
      methodology to deliver 11 case-based pain assessment learning scenarios,
      developed by an interdisciplinary expert panel and delivered to participants'
      work emails over a 28-day period in mid-2012. The 'Self-Perceived Pain Assessment
      Competencies' survey and chart audit data, including patient-reported pain
      intensity ratings, were collected pre-intervention (T1) and post-intervention
      (T2) and analysed using inferential statistics to determine key outcomes.
      SETTING/PARTICIPANTS: Nurses working at two Australian inpatient specialist
      palliative care services in 2012. RESULTS: The results reported conform to the
      Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      Guidelines. Participants who completed the education intervention ( n = 34)
      increased their pain assessment knowledge, assessment tool knowledge and
      confidence to undertake a pain assessment ( p < 0.001). Participants were more
      likely to document pain intensity scores in patients' medical records than non
      participants (95% confidence interval = 7.3%-22.7%, p = 0.021). There was also a
      significant reduction in the mean patient-reported pain ratings between the
      admission and audit date at post-test of 1.5 (95% confidence interval = 0.7-2.3)
      units in pain score. CONCLUSION: This pilot confers confidence of the education
      interventions capacity to improve specialist palliative care nurses' pain
      assessment practices and to reduce patient-rated pain intensity scores.

PMID- 24685650
TI  - Nasogastric tube insertion followed by intravenous and oral erythromycin in
      refractory nausea and vomiting secondary to paraneoplastic gastroparesis: A case
      report.
AB  - BACKGROUND: Gastroparesis is an under-recognised cause of refractory nausea and
      vomiting in patients with malignancy. The most common aetiologies are
      paraneoplastic and postsurgical dysmotility. There are little data on the
      efficacy of treatment to direct the management of patients with this symptom. We
      present a case and brief summary of current literature. CASE PRESENTATION: We
      present the case of a 72-year-old patient with metastatic neuroendocrine
      carcinoma of the pancreas with dehydration and renal impairment secondary to
      nausea and vomiting. Replacement of duodenal stent, gastroscopy, endoscopic
      retrograde cholangiopancreatogram and gastric motility studies revealed
      gastroparesis rather than mechanical obstruction. CASE MANAGEMENT: The patient
      was transferred to an inpatient palliative care unit for symptom management where
      a nasogastric tube was inserted, followed by intravenous erythromycin with
      excellent improvement in symptoms and oral intake. He was switched to oral
      erythromycin with ongoing effect. CASE OUTCOME: With stabilisation of symptoms
      and renal function, the patient was able to be discharged with maintenance of
      good symptomatic control. CONCLUSIONS: Further research is needed into the
      management of gastroparesis in palliative care patients. In particular, we
      suggest that initial drainage with a nasogastric tube followed by a course of
      erythromycin warrants further study.

PMID- 24685651
TI  - The effect of nicotine on osteoinduction by recombinant human bone morphogenetic
      protein 2.
AB  - Nicotine, one of the constituents of tobacco, is known to have an adverse effect
      on human health. We sought to clarify the interaction between nicotine and
      recombinant human bone morphogenetic protein 2 (rhBMP-2) in terms of osteogenesis
      in vitro and osteoinduction in vivo. Nicotine did not inhibit or stimulate
      alkaline phosphatase (ALP) activity or the amount of osteocalcin in C2C12 cells
      in the presence of rhBMP-2 in vitro. Ectopic bone formation using a collagen
      sponge containing rhBMP-2 was evaluated with and without nicotine after 21 days
      using radiographic, histological, biochemical, and immunohistochemical analyses.
      ALP activity in the medium-dose group (2.2+/-0.9IU/mg protein; P=0.047) and the
      high-dose group (2.0+/-0.1IU/mg protein; P=0.03) was significantly lower than in
      the control group. The calcium content in the medium-dose group (35.4+/
      12.9MUg/mg tissue; P=0.0099) and high-dose group (34.8+/-10.5MUg/mg tissue;
      P=0.006) was significantly lower than in the control group. The number of
      vascular endothelial growth factor-positive cells in the high-dose group (671.9+/
      57.3cells/mm(2); P=0.03) was significantly lower than in the control group.
      Results showed that nicotine did not inhibit the stimulatory effect of rhBMP-2 in
      vitro, but a high dose of nicotine inhibited bone formation in vivo by adversely
      affecting vascularization. 

PMID- 24685652
TI  - Comment on the paper by Abbo et al. entitled 'Delayed diagnosis of neurologic
      bladder following spinal cord injury without radiologic abnormality'.

PMID- 24685653
TI  - Enhanced levels of S-linalool by metabolic engineering of the terpenoid pathway
      in spike lavender leaves.
AB  - Transgenic Lavandula latifolia plants overexpressing the linalool synthase (LIS)
      gene from Clarkia breweri, encoding the LIS enzyme that catalyzes the synthesis
      of linalool were generated. Most of these plants increased significantly their
      linalool content as compared to controls, especially in the youngest leaves,
      where a linalool increase up to a 1000% was observed. The phenotype of increased
      linalool content observed in young leaves was maintained in those T1 progenies
      that inherit the LIS transgene, although this phenotype was less evident in the
      flower essential oil. Cross-pollination of transgenic spike lavender plants
      allowed the generation of double transgenic plants containing the DXS (1-deoxy-d
      xylulose-5-P synthase), coding for the first enzyme of the methyl-d-erythritol-4
      phosphate pathway, and LIS genes. Both essential oil yield and linalool content
      in double DXS-LIS transgenic plants were lower than that of their parentals,
      which could be due to co-suppression effects linked to the structures of the
      constructs used. 

PMID- 24685654
TI  - In vivo evolution of metabolic pathways by homeologous recombination in mitotic
      cells.
AB  - We describe a rapid and highly efficient method for the assembly, recombination,
      targeted chromosomal integration and regulatable expression of mosaic metabolic
      pathways by homeologous recombination in DNA repair deficient yeast cells. We
      have assembled and recombined 23kb pathways containing all the genes encoding
      enzymes for the production of flavonoids, a group of plant secondary metabolites
      of nutritional and agricultural value. The mosaic genes of the pathways resulted
      from pair-wise recombination of two nonidentical (homeologous) wild-type genes.
      The recombination events occurred simultaneously in the cell. Correctly assembled
      mosaic gene clusters could only be observed in DNA repair deficient strains.
      Thus, libraries of intragenic mosaic pathways were generated. Randomly isolated
      clones were screened for their ability to produce flavonoids such as kaempferol,
      phloretin and galangin. Thus, the functionality of the recombinant pathways was
      proven. Additionally, significant higher concentrations of metabolites such as
      naringenin, pinocembrin and dihydrokaempferol were detected. Further analysis
      also revealed the production of different aromatic compounds such as styrene,
      hydroxystyrene, phloretic acid and other molecules. We show that the in vivo
      homeologous recombination strategy can generates libraries of intragenic mosaic
      pathways producing a high diversity of phenylpropanoid compounds. 

PMID- 24685657
TI  - Thermodynamic stability contributes to immunoglobulin specificity.
AB  - Antigen-binding specificity of immunoglobulins is important for their function in
      immune defense. However, immune repertoires contain a considerable fraction of
      immunoglobulins with promiscuous binding behavior, the physicochemical basis of
      which is not well understood. Evolution of immunoglobulin specificity occurs
      through iterative processes of mutation and selection, referred to as affinity
      maturation. Recent studies reveal that some somatic mutations could compromise
      the thermodynamic stability of the variable regions of immunoglobulins. By
      integrating this observation with the wealth of data on the evolution of novel
      enzyme activities, we propose that antibody specificity is linked to the
      thermodynamic stability of the antigen-binding regions, which provides a
      quantitative distinction between highly specific and promiscuous antibodies. 

PMID- 24685658
TI  - Blepharospasm with non-satisfactory response to treatment: our experience with
      IncobotulinumtoxinA.

PMID- 24685659
TI  - The factor structure of the UPDRS motor scores changes during early Parkinson's
      disease.
AB  - BACKGROUND: Parkinson's disease is a progressive movement disorder recognized by
      motor symptoms which frequently are measured and longitudinally monitored using
      the Unified Parkinson Disease Rating Scale (UPDRS). The factor structure of the
      UPDRS has yet not been analyzed in early PD. METHODS: A population-based cohort
      of patients with PD was investigated at the time of diagnosis, one year and three
      years later. The factor structure of the motor section of the UPDRS was explored
      using Principal Component Analysis (PCA). RESULTS: We found that the factor
      structure, the interrelatedness among variables, is different in the first year
      from diagnosis compared to later stages, but evolves at three years to resemble
      the factor structure reported for more advanced PD. The only consistent factor
      throughout the observation period was an axial factor. CONCLUSION: The factor
      structure differs in early versus more advanced PD, but resembles the factor
      structure of more advanced PD after three years. This is likely due to a higher
      proportion of subjects with unilateral motor symptoms in early stages of PD
      together with a changing distribution of motor symptoms with further disease
      progression. Initiation of PD medication did not alter the factor structure in
      early PD. The axial factor was the most consistent factor in early PD and could
      be the most appropriate factor to monitor progression across the earliest stages
      of PD.

PMID- 24685660
TI  - Clinically discriminating checklists versus thoroughness checklists: improving
      the validity of performance test scores.
AB  - PURPOSE: High-quality checklists are essential to performance test score
      validity. Prior research found that physical exam checklists of items that
      clinically discriminated between competing diagnoses provided more generalizable
      scores than all-encompassing thoroughness checklists. The purpose of this study
      was to compare validity evidence for clinically discriminating versus
      thoroughness checklists, hypothesizing that evidence would favor the former.
      METHOD: Faculty at four Chicago-area medical schools developed six standardized
      patient (SP) cases with checklists of about 20 items ("thoroughness [long]
      checklists"). Four clinicians identified a subset of items that clinically
      discriminated between competing diagnoses of each case ("clinically
      discriminating [short] checklists"). Cases were administered to 155 University of
      Illinois at Chicago fourth-year medical students during their 2011 Clinical
      Skills Examination (CSE). Validity evidence was compared for CSE scores based on
      thoroughness versus clinically discriminating checklist items. RESULTS: Validity
      evidence favoring clinically discriminating checklists included response process:
      greater SP checklist accuracy (kappa = 0.75 for long and 0.84 for short
      checklists, P < .05); internal structure: better item discrimination (0.28 long,
      0.42 short, P < .001); internal consistency reliability (0.80 long, 0.92 short);
      standard error of measurement (z score 8.87 long, 8.05 short); and
      generalizability (G = 0.504 long, 0.533 short). There were no significant
      differences overall in relevance ratings, item difficulty, or cut scores of long
      versus short checklist items. CONCLUSIONS: Limiting checklist items to those
      affecting diagnostic decisions resulted in better accuracy and psychometric
      indices. Thoroughness items performed without thinking do not reflect clinical
      reasoning ability and contribute construct-irrelevant variance to scores.

PMID- 24685662
TI  - Essays on citation classics in Cardiology.

PMID- 24685661
TI  - Psychological correlates to dysfunctional eating patterns among morbidly obese
      patients accepted for bariatric surgery.
AB  - OBJECTIVE: To examine the relationships between dysfunctional eating patterns,
      personality, anxiety and depression in morbidly obese patients accepted for
      bariatric surgery. DESIGN: The study used cross-sectional data collected by
      running a randomized controlled trial
      (http://clinicaltrials.gov/ct2/show/NCT01403558). SUBJECTS: A total of 102
      patients (69 women, 33 men) with a mean (SD) age of 42.6 (9.8) years and a mean
      BMI of 43.5 (4.4) kg/m(2) participated. MEASUREMENTS: Measurements included the
      NEO-PI-R (personality: neuroticism, extroversion, openness, conscientiousness and
      agreeableness), the TFEQ-R-21 (dysfunctional eating: emotional eating (EE),
      uncontrolled eating (UE) and cognitive restraint of eating (CR)) and the HADS
      (anxiety and depression). RESULTS: The personality traits neuroticism and
      conscientiousness were more strongly correlated with dysfunctional eating than
      anxiety and depression. These differences were most pronounced for emotional and
      cognitive restraint of eating. Emotional eating occurred more often in female
      than in male patients, a finding that was partially mediated by neuroticism but
      not by anxiety and depression. CONCLUSION: Personality traits may be important to
      address in the clinical management of morbidly obese patients seeking bariatric
      surgery as neuroticism is particularly salient in female patients displaying an
      emotional eating behaviour.

PMID- 24685663
TI  - Balancing innovation and harm.

PMID- 24685664
TI  - Magnetic Resonance Imaging Tracking of Graft Survival in the Infarcted Heart:
      Iron Oxide Particles Versus Ferritin Overexpression Approach.
AB  - The main objective of cell therapy is the regeneration of damaged tissues. To
      distinguish graft from host tissue by magnetic resonance imaging (MRI), a
      paramagnetic label must be introduced to cells prior to transplantation. The
      paramagnetic label can be either exogenous iron oxide nanoparticles or a genetic
      overexpression of ferritin, an endogenous iron storage protein. The purpose of
      this work was to compare the efficacy of these 2 methods for MRI evaluation of
      engrafted cell survival in the infarcted mouse heart. Mouse skeletal myoblasts
      were labeled either by cocultivation with iron oxide particles or by engineering
      them to overexpress ferritin. Along with live cell transplantation, 2 other
      groups of mice were injected with dead-labeled cells. Both particle-labeled and
      ferritin-tagged grafts were detected as areas of MRI signal hypointensity in the
      left ventricle of the mouse heart using T2*-weighted sequences, although the
      signal attenuation decreased with ferritin tagging. Importantly, live cells could
      not be distinguished from dead cells when labeled with iron oxide particles,
      whereas the ferritin tagging was detected only in live grafts, thereby allowing
      identification of viable grafts using MRI. Thus, iron oxide particles can provide
      information about initial cell injection success but cannot assess graft
      viability. On the other hand, genetically based cell tagging, such as ferritin
      overexpression, despite having lower signal intensity in comparison with iron
      oxide particles, is able to identify live transplanted cells.

PMID- 24685666
TI  - Functional reorganization of the forepaw cortical representation immediately
      after thoracic spinal cord hemisection in rats.
AB  - Spinal cord injury may produce long-term reorganization of cortical circuits.
      Little is known, however, about the early neurophysiological changes occurring
      immediately after injury. On the one hand, complete thoracic spinal cord
      transection of the spinal cord immediately decreases the level of cortical
      spontaneous activity and increases the cortical responses to stimuli delivered to
      the forepaw, above the level of the lesion. On the other hand, a thoracic spinal
      cord hemisection produces an immediate cortical hyperexcitability in response to
      preserved spinothalamic inputs from stimuli delivered to the hindpaw, below the
      level of the lesion. Here we show that a thoracic spinal cord hemisection also
      produces a bilateral increase of the responses evoked in the forepaw cortex by
      forepaw stimuli, associated with a bilateral decrease of cortical spontaneous
      activity. Importantly, the increased cortical forepaw responses are immediate in
      the cortex contralateral to the hemisection (significant within 30min after
      injury), but they are progressive in the cortex ipsilateral to the hemisection
      (reaching significance only 2.5h after injury). Conversely, the decreased
      cortical spontaneous activity is progressive both ipsilaterally and
      contralaterally to the hemisection (again reaching significance only 2.5h after
      injury). In synthesis, the present work reports a functional reorganization of
      the forepaw cortical representation immediately after thoracic spinal cord
      hemisection, which is likely important to fully understand the mechanisms
      underlying long-term cortical reorganization after incomplete spinal cord
      injuries. 

PMID- 24685665
TI  - Early-life seizures result in deficits in social behavior and learning.
AB  - Children with epilepsy show a high co-morbidity with psychiatric disorders and
      autism. One of the critical determinants of a child's behavioral outcome with
      autism and cognitive dysfunction is the age of onset of seizures. In order to
      examine whether seizures during postnatal days 7-11 result in learning and memory
      deficits and behavioral features of autism we administered the inhalant flurothyl
      to induce seizures in C57BL/6J mice. Mice received three seizures per day for
      five days starting on postnatal day 7. Parallel control groups consisted of
      similarly handled animals that were not exposed to flurothyl and naive mice.
      Subjects were then processed through a battery of behavioral tests in adulthood:
      elevated-plus maze, nose-poke assay, marble burying, social partition, social
      chamber, fear conditioning, and Morris water maze. Mice with early-life seizures
      had learning and memory deficits in the training portion of the Morris water maze
      (p<0.05) and probe trial (p<0.01). Mice with seizures showed no differences in
      marble burying, the nose-poke assay, or elevated plus-maze testing compared to
      controls. However, they showed a significant difference in the social chamber and
      social partition tests. Mice with seizures during postnatal days 7-11 showed a
      significant decrease in social interaction in the social chamber test and had a
      significant impairment in social behavior in the social partition test. Together,
      these results indicate that early life seizures result in deficits in hippocampal
      dependent memory tasks and produce long-term disruptions in social behavior. 

PMID- 24685667
TI  - ACC/AHA/SCAI 2014 health policy statement on structured reporting for the cardiac
      catheterization laboratory: a report of the American College of Cardiology
      Clinical Quality Committee.

PMID- 24685669
TI  - 2014 AHA/ACC/HRS guideline for the management of patients with atrial
      fibrillation: a report of the American College of Cardiology/American Heart
      Association Task Force on Practice Guidelines and the Heart Rhythm Society.

PMID- 24685670
TI  - Delayed diagnosis of neurological bladder following spinal cord injury without
      radiological abnormality.
AB  - Spinal cord injuries are a well-known cause of neurological bladder and a well
      known complication of high-velocity trauma. They can, however, be difficult to
      diagnose in young children, in whom the absence of initial neurological symptoms
      and normality of the radiological workup can be falsely reassuring. Management of
      associated injuries can further delay diagnosis. We present 2 cases of spinal
      cord injuries without radiological abnormality revealed by delayed bladder
      retention.

PMID- 24685672
TI  - Internal derangement of the knee in fibular hemimelia: radiographic and MRI
      findings.
AB  - BACKGROUND: Fibular hemimelia is a rare bone dysplasia with partial or complete
      absence of the fibula. There are many associated lower limb deformities. METHODS:
      We describe the commonly associated bone and soft tissue abnormalities in the
      knee joint in a case series of six knees in five patients with fibular hemimelia
      who underwent both radiographic and MR imaging. RESULTS: In all knees, there was
      an elongated conjoint tendon of the lateral collateral ligament and biceps
      femoris. In five out of six knees, there was trochlear dysplasia. In four out of
      six, there was complete absence of the anterior cruciate ligament. In four out of
      six, there was an abnormal lateral meniscus (three were hypoplastic and one
      absent). CONCLUSION: These associations in fibular hemimelia, although
      unpredictable, have relevance in the guidance of further orthopaedic management
      in this complex condition.

PMID- 24685671
TI  - Liver transplantation: immunosuppression and oncology.
AB  - PURPOSE OF REVIEW: Long-term survival of liver transplant recipients is
      threatened by increased rates of de-novo malignancy and recurrence of
      hepatocellular carcinoma (HCC), both events tightly related to immunosuppression.
      RECENT FINDINGS: There is accumulating evidence linking increased exposure to
      immunosuppressants and carcinogenesis, particularly concerning calcineurin
      inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study
      including 219 HCC transplanted patients showed that HCC recurrence rates were
      halved if a minimization of CNIs was applied within the first month after liver
      transplant. With mammalian target of rapamycin (mTOR) inhibitors as approved
      immunosuppressants for liver transplant patients, pooled data from several
      retrospective studies have suggested their possible benefit for reducing HCC
      recurrence. SUMMARY: Randomized controlled trials with sufficiently long follow
      up are needed to evaluate the influence of different immunosuppression protocols
      in preventing malignancy after LT. Currently, early minimization of CNIs with or
      without mTOR inhibitors or mycophenolate seems a rational strategy for patients
      with risk factors for de-novo malignancy or recurrence of HCC after liver
      transplant. A deeper understanding of the immunological pathways of rejection and
      cancer would allow for designing more specific and safer drugs, and thus to
      prevent cancer after liver transplant.

PMID- 24685673
TI  - Characterization of an avirulent FCV strain with a broad serum cross
      neutralization profile and protection against challenge of a highly virulent vs
      feline calicivirus.
AB  - Highly virulent, systemic strains of Feline calicivirus (vs FCV) have been
      described in recent years. These vs FCV isolates cause severe edema, cutaneous
      ulcers, lameness and other upper respiratory and oral clinical signs typically
      associated with FCV infection in cats. Vs FCV isolates can cause high mortality
      even in cats vaccinated with currently available commercial vaccines. This study
      reports identification and characterization of an avirulent FCV strain (FCV 21).
      This strain offers a broader serum cross-neutralization profile in comparison
      with the commonly used vaccine strain (FCV F9), as tested with two separate viral
      panels of FCV isolates. The first viral panel consists of 45 FCV strains isolated
      around 1993. The second viral panel consists of 26 FCV strains with most isolated
      around 2003. The potential of using this strain as a vaccine, in a 3-way
      (FCV+FHV+FPV) or 4-way (FCV+FHV+FPV+FCp) format, was tested by using a highly
      virulent vs FCV strain (FCV-33585) as a challenge virus. The mortality induced by
      this vs FCV in unvaccinated control cats was 78% (7 out of 9 cats). The mortality
      decreased to 44% (4 out of 9 cats) in cats vaccinated with a 4-way vaccine
      containing FCV F9. However, when this novel FCV vaccine strain (FCV 21) was used,
      either in combination with FCV F9 or by itself, the mortality decreased to 0% (0
      out of 10 cats). The 3-way vaccine (FCV+FHV+FPV) that contained both FCV 21 and
      FCV F9 also had mortality of 0% (0 out of 10 cats). The clinical scores, as
      calculated taking into consideration the frequency and severity of various
      clinical signs, correlated with mortality data. The results suggested this FCV
      vaccine has the potential to be broadly protective against newly emergent FCV
      isolates, including complete protection against challenge with a highly virulent
      vs FCV 33585.

PMID- 24685674
TI  - Deep sequencing of pigeonpea sterility mosaic virus discloses five RNA segments
      related to emaraviruses.
AB  - The sequences of five viral RNA segments of pigeonpea sterility mosaic virus
      (PPSMV), the agent of sterility mosaic disease (SMD) of pigeonpea (Cajanus cajan,
      Fabaceae), were determined using the deep sequencing technology. Each of the five
      RNAs encodes a single protein on the negative-sense strand with an open reading
      frame (ORF) of 6885, 1947, 927, 1086, and 1,422 nts, respectively. In order, from
      RNA1 to RNA5, these ORFs encode the RNA-dependent RNA polymerase (p1, 267.9 kDa),
      a putative glycoprotein precursor (p2, 74.3 kDa), a putative nucleocapsid protein
      (p3, 34.6 kDa), a putative movement protein (p4, 40.8 kDa), while p5 (55 kDa) has
      an unknown function. All RNA segments of PPSMV showed the highest identity with
      orthologs of fig mosaic virus (FMV) and Rose rosette virus (RRV). In phylogenetic
      trees constructed with the amino acid sequences of p1, p2 and p3, PPSMV clustered
      consistently with other emaraviruses, close to clades comprising members of other
      genera of the family Bunyaviridae. Based on the molecular characteristics
      unveiled in this study and the morphological and epidemiological features similar
      to other emaraviruses, PPSMV seems to be the seventh species to join the list of
      emaraviruses known to date and accordingly, its classification in the genus
      Emaravirus seems now legitimate.

PMID- 24685675
TI  - Molecular characterization of the complete genome of falconid herpesvirus strain
      S-18.
AB  - Falconid herpesvirus type 1 (FaHV-1) is the causative agent of falcon inclusion
      body disease, an acute, highly contagious disease of raptors. The complete
      nucleotide sequence of the genome of FaHV-1 has been determined using Illumina
      MiSeq sequencing. The genome is 204,054 nucleotides in length and has a class E
      organization. The genome encodes approximately 130 putative protein-coding genes,
      of which 70 are orthologs of conserved alphaherpesvirus and Mardivirus proteins.
      Three FaHV-1 genes (UL3.5, UL44.5 and CIRC) were identified that encode protein
      homologues unique to Mardivirus and Varicellovirus. The genome also encodes
      homologues to the Mardivirus genes LORF2, LORF3, LORF4, LORF5, SORF3 and SORF4.
      An opal mutation resulting in premature termination was identified in the FaHV-1
      UL43 gene. Phylogenetically, FaHV-1 resides in a monophyletic group with the
      other Mardiviruses but, along with anatid herpesvirus 1, represents a more
      distant divergence from the rest of the Mardivirus genus.

PMID- 24685677
TI  - Biosynthesis of cystic fibrosis transmembrane conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP
      regulated chloride (Cl(-)) channel. Mutations of its gene lead to the disease of
      cystis fibrosis (CF) among which the most common is the deletion of phenylalanine
      at position 508 (Phe508del). CFTR is a multi-domain glycoprotein whose
      biosynthesis, maturation and functioning as an anion channel involve multi-level
      post-translational modifications of CFTR molecules and complex folding processes
      to reach its native, tertiary conformation. Only 20-40% of the nascent chains
      achieve folded conformation, while the remaining molecules are targeted for
      degradation by endoplasmic reticulum, lysosomes, or autophagy. A large number of
      mutations causing CF impair processing of CFTR. Growing knowledge of CFTR
      biosynthesis has enabled understanding the cellular basis of CF and has brought
      to light various potential targets for novel, promising therapies.

PMID- 24685678
TI  - Fibroblasts induce epithelial to mesenchymal transition in breast tumor cells
      which is prevented by fibroblasts treatment with histamine in high concentration.
AB  - Epithelial to mesenchymal transition (EMT) of cancer cells is an essential
      process in cancer progression. Cancer cells that undergone EMT loose cell-cell
      contacts, acquire mesenchymal properties and develop migratory and invasive
      abilities. In previous studies we have demonstrated that histamine may modify the
      invasive phenotype of pancreatic and mammary tumor cells. In this work we
      proposed to investigate whether histamine may also influence the interaction
      between tumor cells and normal fibroblasts. The potential activation of normal
      CCD-1059Sk fibroblasts by histamine and EMT phenotypic changes induced in MCF-7
      and MDA-MB-231 breast tumor cells by the conditioned media (CM) derived from
      fibroblasts were evaluated. Initially, we determined the presence of H1, H2 and
      H4 histamine receptors and matrix metalloproteinase 2 (MMP2) mRNA in CCD-1059Sk
      fibroblasts. MMP2 gelatinolytic activity, cell migration and alpha-smooth muscle
      actin expression were increased in fibroblasts by low doses (<1MUM) and decreased
      by high doses (20MUM) of histamine. MCF-7 cells cultured with CM from fibroblasts
      exhibited spindle-shaped morphology, cell spreading and cytoplasmic expression of
      beta-catenin but there was no change in MMP2 activity and cell migration. MDA-MB
      231 cells cultured with CM from fibroblasts showed a more elongated phenotype,
      cell spreading, cytoplasmic beta-catenin, increased MMP2 activity and endogenous
      TGF-beta1 expression, and enhanced cell migration and invasion. Notably, all
      these features were reversed when mammary tumor cells were cultured with CM from
      fibroblasts treated with 20MUM histamine. In conclusion, high doses of histamine
      may prevent the activation of fibroblasts and also avert the EMT related changes
      induced in epithelial tumor cells by fibroblasts CM. 

PMID- 24685676
TI  - Cystic fibrosis: an inherited disease affecting mucin-producing organs.
AB  - Our current understanding of cystic fibrosis (CF) has revealed that the
      biophysical properties of mucus play a considerable role in the pathogenesis of
      the disease in view of the fact that most mucus-producing organs are affected in
      CF patients. In this review, we discuss the potential causal relationship between
      altered cystic fibrosis transmembrane conductance regulator (CFTR) function and
      the production of mucus with abnormal biophysical properties in the intestine and
      lungs, highlighting what has been learned from cell cultures and animal models
      that mimic CF pathogenesis. A similar cascade of events, including mucus
      obstruction, infection and inflammation, is common to all epithelia affected by
      impaired surface hydration. Hence, the main structural components of mucus,
      namely the polymeric, gel-forming mucins, are critical to the onset of the
      disease. Defective CFTR leads to epithelial surface dehydration, altered
      pH/electrolyte composition and mucin concentration. Further, it can influence
      mucin transition from the intracellular to extracellular environment, potentially
      resulting in aberrant mucus gel formation. While defective HCO3(-) production has
      long been identified as a feature of CF, it has only recently been considered as
      a key player in the transition phase of mucins. We conclude by examining the
      influence of mucins on the biophysical properties of CF sputum and discuss
      existing and novel therapies aimed at removing mucus from the lungs. This article
      is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell
      biology, physiology, and therapeutic advances. 

PMID- 24685679
TI  - Neutrophil Elastase in the capacity of the "H2A-specific protease".
AB  - The amino-terminal tail of histones and the carboxy-tail of histone H2A protrude
      from the nucleosome and can become modified by many different posttranslational
      modifications (PTM). During a mass spectrometric proteome analysis on
      haematopoietic cells we encountered a histone PTM that has received only little
      attention since its discovery over 35 years ago: truncation of the histone H2A C
      tail at V114 which is mediated by the "H2A specific protease" (H2Asp). This
      enzyme is still referenced today but it was never identified. We first developed
      a sensitive AQUA approach for specific quantitation of the H2AV114 clipping. This
      clipping was found only in myeloid cells and further cellular fractionation lead
      to the annotation of the H2Asp as Neutrophil Elastase (NE). Ultimate proof was
      provided by NE incubation experiments and by studying histone extracts from NE
      Null mice. The annotation of the H2Asp not only is an indispensable first step in
      elucidating the potential biological role of this enzymatic interaction but
      equally provides the necessary background to critically revise earlier reports of
      H2A clipping. 

PMID- 24685680
TI  - Interactions of ataxin-3 with its molecular partners in the protein machinery
      that sorts protein aggregates to the aggresome.
AB  - Ataxin-3 (AT3) is the protein that triggers the inherited neurodegenerative
      disorder spinocerebellar ataxia type 3 when its polyglutamine (polyQ) stretch
      close to the C-terminus exceeds a critical length. AT3 consists of the N-terminal
      globular Josephin domain (JD) and the C-terminal disordered one. It cleaves
      isopeptide bonds between ubiquitin monomers, an event involved in protein quality
      control mechanisms. AT3 has been implicated in the pathway that sorts aggregated
      protein to aggresomes via microtubules, in which dynein and histone deacetylase 6
      (HDAC6) also seem to be involved. By taking advantage of small angle X-ray
      scattering (SAXS) and surface plasmon resonance (SPR), we have investigated the
      interaction of AT3 with tubulin and HDAC6. Based on SAXS results, the AT3
      oligomer, consisting of 6-7 subunits, tightly binds to the tubulin hexameric
      oligomer in a "parallel" fashion. By SPR analysis we have demonstrated that AT3
      binds to tubulin dimer with a 50nM affinity. Binding fits with a Langmuir 1:1
      model and involves a single binding interface. Nevertheless, the interaction
      surface consists of three distinct, discontinuous tubulin-binding regions (TBR),
      one located in the JD, and the two others in the disordered domain, upstream and
      downstream of the polyQ stretch. In the absence of any of the three TBRs, the
      affinity is drastically reduced. By SPR we have also provided the first evidence
      of direct binding of AT3 to HDAC6, with affinity in the range 0.1-1MUM. These
      results shed light on the interactions among the components of the transport
      machinery that sorts aggregate protein to the aggresome, and pave the way to in
      vivo studies aimed at further clarifying their roles. 

PMID- 24685681
TI  - Cytoskeleton and CFTR.
AB  - Cystic Fibrosis Transmembrane conductance Regulator, CFTR, is a membrane protein
      expressed in epithelia. A protein kinase A (PKA)-regulated Cl(-) channel, it is a
      rate-limiting factor in fluid transport. Mutations in CFTR are responsible for
      cystic fibrosis, CF, an autosomal recessive disease. The most frequent mutation
      is deletion of phenylalanine at position 508, DeltaF508. The regulation of
      trafficking and degradation of CFTR/DeltaF508CFTR as well as its function(s) is a
      complex process which involves a number of proteins including chaperones and
      adaptors. It is now known that cytoskeletal proteins, previously considered only
      as structural proteins, are also important factors in the regulation of cellular
      processes and functions. The aim of the present review is to focus on how
      microfilaments, microtubules and intermediary filaments form a dynamic
      interactome with CFTR to participate in the regulation of CFTR-dependent
      transepithelial ion transport, CFTR trafficking and degradation.

PMID- 24685682
TI  - Simple and rapid method for the detection of Filobasidiella neoformans in a
      probiotic dairy product by using loop-mediated isothermal amplification.
AB  - Yeast contamination is a serious problem in the food industry and a major cause
      of food spoilage. Several yeasts, such as Filobasidiella neoformans, which cause
      cryptococcosis in humans, are also opportunistic pathogens, so a simple and rapid
      method for monitoring yeast contamination in food is essential. Here, we
      developed a simple and rapid method that utilizes loop-mediated isothermal
      amplification (LAMP) for the detection of F. neoformans. A set of five specific
      LAMP primers was designed that targeted the 5.8S-26S rDNA internal transcribed
      spacer 2 region of F. neoformans, and the primer set's specificity was confirmed.
      In a pure culture of F. neoformans, the LAMP assay had a lower sensitivity
      threshold of 10(2)cells/mL at a runtime of 60min. In a probiotic dairy product
      artificially contaminated with F. neoformans, the LAMP assay also had a lower
      sensitivity threshold of 10(2)cells/mL, which was comparable to the sensitivity
      of a quantitative PCR (qPCR) assay. We also developed a simple two-step method
      for the extraction of DNA from a probiotic dairy product that can be performed
      within 15min. This method involves initial protease treatment of the test sample
      at 45 degrees C for 3min followed by boiling at 100 degrees C for 5min under
      alkaline conditions. In a probiotic dairy product artificially contaminated with
      F. neoformans, analysis by means of our novel DNA extraction method followed by
      LAMP with our specific primer set had a lower sensitivity threshold of
      10(3)cells/mL at a runtime of 60min. In contrast, use of our novel method of DNA
      extraction followed by qPCR assay had a lower sensitivity threshold of only
      10(5)cells/mL at a runtime of 3 to 4h. Therefore, unlike the PCR assay, our LAMP
      assay can be used to quickly evaluate yeast contamination and is sensitive even
      for crude samples containing bacteria or background impurities. Our study
      provides a powerful tool for the primary screening of large numbers of food
      samples for yeast contamination. 

PMID- 24685683
TI  - The influence of salt (NaCl) on ochratoxin A biosynthetic genes, growth and
      ochratoxin A production by three strains of Penicillium nordicum on a dry-cured
      ham-based medium.
AB  - Iberian dry-cured ham is colonised by moulds during the ripening process. The
      environmental conditions occurring during the process including the salt content
      predisposes the surface to colonisation by Penicillium species, including
      Penicillium nordicum which can contaminate the curing ham with ochratoxin A
      (OTA). The objective of this study was to examine the effect of NaCl (10% and
      22%=0.94 and 0.87 water activity (aw)) on the activation of two genes involved in
      the biosynthetic pathway for OTA production, otapksPN and otanpsPN, relative
      growth and phenotypic OTA production by three strains of P. nordicum (CBS
      110.769, FHSCC1 and FHSCC2) on a ham-based medium over a period of 12days at 25
      degrees C. Growth of the three strains was faster at 0.87 than 0.94 aw on the ham
      based media. However, some intra- and inter-strain differences were observed. Of
      the three strains, only two (CBS 110.789; FHSCC2) were able to express the two
      genes involved in the biosynthesis of OTA in the two salt treatments. RT-qPCR
      showed that the temporal expression of the two genes (otapksPN and otanpsPN) was
      relatively similar for the wild type strain (FHSCC2) at both 0.94 and 0.87 aw
      over the 12day period. However, in the type strain (CBS 110.769) expression
      increased rapidly at 0.94 aw but was significantly lower at 0.87 aw. Expression
      of these two genes occurred after 3day incubation, while phenotypic OTA
      production was observed only after 6days in the two toxigenic strains. The other
      strain did not produce any OTA. The OTA concentrations confirmed the results
      observed with the molecular tools. This suggests that the RT-qPCR gene expression
      of these two genes may be a good early indicator of potential contamination of
      dry-cured ham with OTA during dry-cured ham ripening. 

PMID- 24685684
TI  - Analysis on micro-regional characters of the resistance wires surface in
      electrical immersion heater by SEM/EDX.
AB  - We present a novel method for identifying the conditions of electrical resistance
      wires before fire basing on micro-regional characters. The morphology and
      elemental compositions of resistance wires surface under normally used, misused
      and external heating conditions were respectively studied by scanning electron
      microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The results show
      that the normally used wire has a smooth surface and stable metal composition.
      While the resistance wire under misused condition for the certain time could be
      characterized as a coarse surface covered by compacted and silica-embedded oxide
      layer, and the proportion of elemental compositions of different metals is also
      changed with higher content of Al and lower content of Fe and Cr. The external
      heating condition has little influence on inside wires. The mechanism of changes
      formed under misused condition was explained. We demonstrate that this approach
      is practical and functional to aid fire investigators in determining the cause of
      related fires. 

PMID- 24685685
TI  - Morphological identification of animal hairs: Myths and misconceptions,
      possibilities and pitfalls.
AB  - The examination of hair collected from crime scenes is an important and highly
      informative discipline relevant to many forensic investigations. However, the
      forensic identification of animal (non-human) hairs requires different skill sets
      and competencies to those required for human hair comparisons. The aim of this is
      paper is not only to highlight the intrinsic differences between forensic human
      hair comparison and forensic animal hair identification, but also discuss the
      utility and reliability of the two in the context of possibilities and pitfalls.
      It also addresses and dispels some of the more popular myths and misconceptions
      surrounding the microscopical examination of animal hairs. Furthermore, future
      directions of this discipline are explored through the proposal of
      recommendations for minimum standards for the morphological identification of
      animal hairs and the significance of the newly developed guidelines by SWGWILD is
      discussed. 

PMID- 24685686
TI  - Predictive value of elevated neutrophil to lymphocyte ratio for long-term
      cardiovascular mortality in peripheral arterial occlusive disease.
AB  - BACKGROUND: Peripheral arterial occlusive disease (PAOD), which is common in male
      gender and elderly population, is related with increased cardiovascular mortality
      and morbidity. Neutrophil to lymphocyte ratio (NLR) has been found to be an
      independent predictor of cardiovascular mortality in atherosclerosis. The aim of
      the present study was to investigate the association between NLR and
      cardiovascular mortality both in patients with intermittent claudication and
      critical limb ischemia. METHODS: In a retrospective study, 593 consecutive
      patients who had been admitted to the inpatient ward of the vascular department
      of a large tertiary training and research hospital with diagnosis of symptomatic
      PAOD between May 2009 and September 2012 were included. Patients were divided
      into two groups according to their NLR as follows: high NLR (NLR>3.0) and low NLR
      (NLR <= 3.0) groups. RESULTS: During the course of the present study [median
      follow-up period of 20 months (interquartile range, 12-27)], 75 deaths occurred
      out of 508 patients (14.8%). Cardiovascular mortality was found to be
      significantly higher in elevated NLR group (n = 43) as compared to low NLR group
      (n = 32) (23.6% vs 9.8%, respectively; p < 0.001). Even after adjustment of
      various risk factors, NLR > 3 and age were found as independent predictors of
      long-term cardiovascular mortality in Cox regression analysis [hazard ratios (95%
      confidence interval), 2.04 (1.26-3.30) and 1.04 (1.01-1.07), p = 0.004 and p =
      0.004, respectively]. CONCLUSION: We demonstrated that an increased NLR was
      related with higher cardiovascular mortality in patients with PAOD, who were
      admitted with critical limb ischemia or intermittent claudication. NLR, which
      reflects the patient's inflammatory status, is an inexpensive and readily
      available biomarker that provides an additional level of risk stratification
      beyond that provided by conventional risk scores in predicting long-term
      cardiovascular mortality in PAOD.

PMID- 24685687
TI  - Association of plasma thioredoxin-1 with renal tubular damage and cardiac
      prognosis in patients with chronic heart failure.
AB  - BACKGROUND: Thioredoxin-1 (Trx-1) is an abundant 12.5 kDa redox protein expressed
      in almost all eukaryotic cells that protect against the development of heart
      failure and kidney dysfunction. Plasma Trx-1 levels are considered as a reliable
      marker for oxidative stress. However, it remains to be determined whether plasma
      Trx-1 levels can predict cardiac prognosis in patients with chronic heart failure
      (CHF). METHODS AND RESULTS: We measured plasma Trx-1 levels and urinary beta2
      microglobulin-creatinine ratio (UBCR), a marker for renal tubular damage, in 156
      consecutive patients with CHF and 17 control subjects. The patients were
      prospectively followed for a median follow-up period of 627 days and 46 cardiac
      events were observed. The patients with cardiac events had significantly higher
      plasma Trx-1 levels and UBCR levels than the cardiac event-free patients.
      Multivariate Cox proportional hazard analysis revealed that an elevated Trx-1
      level was independently associated with poor outcome in patients with CHF after
      adjustment for confounding factors (hazard ratio, 1.74; 95% confidence interval,
      1.33-2.29; p < 0.0001). UBCR was increased with higher plasma Trx-1 levels.
      Kaplan-Meier analysis demonstrated that the highest Trx-1 tertile was associated
      with the highest risk of cardiac events. CONCLUSION: Plasma Trx-1 level was
      associated with renal tubular damage and cardiac prognosis, suggesting that it
      could be a useful marker to identify patients at high risk for comorbid heart
      failure and renal tubular damage.

PMID- 24685688
TI  - Disease duration and severity impacts on long-term cardiovascular events in
      Japanese patients with rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) increases the mortality and morbidity of
      cardiovascular disease (CVD). However, the relationship between RA and the risk
      of CVD in the Japanese population remains unclear. METHODS AND RESULTS: This
      study comprised 571 RA patients who were admitted to Juntendo University Hospital
      from January 1990 to December 2000. Cardiovascular events (CVEs) were defined as
      cardiac death, acute coronary syndrome (ACS), symptomatic stroke, and congestive
      heart failure. During follow-up (mean 11.7 +/- 5.8 years), 7.5% of the patients
      died from all causes and 11.0% experienced CVEs. The morbidity of stroke and ACS
      was 3.6 and 2.5 per 1000 person-years, respectively. The mean RA disease duration
      at enrolment was significantly longer in patients who experienced CVEs than in
      those who did not experience CVEs (15.0 +/- 12.7 years vs. 10. 8 +/- 9.7 years; p
      = 0.01). Physical disabilities due to RA were more severe in patients who
      experienced CVEs than in those who did not experience CVEs. Patients with a long
      RA disease duration showed significantly higher event rates (p = 0.033). Cox
      proportional hazards analysis identified a longer RA duration as an independent
      risk factor for CVD (hazard ratio 1.57, 95% CI 1.09-2.30, p = 0.02). CONCLUSION:
      Japanese RA patients showed a relatively high incidence of CVD, despite the fact
      that they had few coronary risk factors. The RA disease duration was an
      independent risk factor for CVEs.

PMID- 24685689
TI  - Drug-eluting versus bare-metal stents in large coronary arteries of patients with
      ST-segment elevation myocardial infarction: findings from the ICAS registry.
AB  - BACKGROUND AND PURPOSE: There are a few retrospective subgroup analyses or
      registries of large-vessel (>= 3.5mm) stenting. We investigated clinical outcomes
      of patients with ST-segment elevation myocardial infarction (STEMI) undergoing
      percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare
      metal stents (BMS) in large coronary vessels. METHODS AND SUBJECTS: Of 1100 STEMI
      patients registered in the Ibaraki Cardiovascular Assessment Study (ICAS)
      multicenter registry from April 2007 to June 2012 who underwent PCI, we enrolled
      454 patients (65.8 +/- 12.7 years old, 81% male) with >= 3.5-mm stents. We
      excluded 53 patients with cardiogenic shock or left main trunk lesions. The
      remaining 401 patients were divided into Group-D, PCI with DES (n = 184), and
      Group-B, PCI with BMS (n = 217). Propensity score analysis matched 1:1 according
      to treatment with DES (n = 101) or with BMS (n = 101). We evaluated major adverse
      cardiac and cerebrovascular events (MACCE) and incidence of stent thrombosis
      (ST). MACCE was defined as all-cause death, myocardial infarction (MI), target
      vessel revascularization (TVR), or cerebrovascular accident (CVA). ESSENTIAL
      RESULTS: During a mean follow-up period of 526 days, all-cause death, MI, CVA,
      MACCE, and ST were not significantly different in Group-D versus Group-B (all
      cause death: 4.35% vs. 4.61%, p = 0.90; MI: 0% vs. 0%; CVA: 2.72% vs. 3.23%, p =
      0.76; MACCE: 15.2% vs. 20.3%, p = 0.19; and ST: 0.0% vs. 1.38%, p = 0.11). After
      adjusting for age, insulin use, multivessel disease, intra-aortic balloon pump
      use, culprit lesions, and estimated glomerular filtration rate <60 ml/min/1.73
      m(2), MACCE was not significantly different between the groups (odds ratio: 0.69;
      95% CI: 0.40-1.23; p = 0.21). However, TVR was significantly lower in Group-D
      than Group-B in Kaplan-Meier analysis (p = 0.048) after propensity score
      matching. PRINCIPAL CONCLUSION: There was no advantage to using a DES in large
      vessels for preventing a hard endpoint, whereas DES use resulted in a significant
      reduction in TVR in the patients with STEMI in this registry.

PMID- 24685690
TI  - Lipid accumulation in dysferlin-deficient muscles.
AB  - Dysferlin is a membrane associated protein involved in vesicle trafficking and
      fusion. Defects in dysferlin result in limb-girdle muscular dystrophy type 2B and
      Miyoshi myopathy in humans and myopathy in A/J(dys-/-) and BLAJ mice, but the
      pathomechanism of the myopathy is not understood. Oil Red O staining showed many
      lipid droplets within the psoas and quadriceps muscles of dysferlin-deficient
      A/J(dys-/-) mice aged 8 and 12 months, and lipid droplets were also conspicuous
      within human myofibers from patients with dysferlinopathy (but not other
      myopathies). Electron microscopy of 8-month-old A/J(dys-/-) psoas muscles
      confirmed lipid droplets within myofibers and showed disturbed architecture of
      myofibers. In addition, the presence of many adipocytes was confirmed, and a
      possible role for dysferlin in adipocytes is suggested. Increased expression of
      mRNA for a gene involved in early lipogenesis, CCAAT/enhancer binding protein
      delta, in 3-month-old A/J(dys-/-) quadriceps (before marked histopathology is
      evident), indicates early induction of lipogenesis/adipogenesis within dysferlin
      deficient muscles. Similar results were seen for dysferlin-deficient BLAJ mice.
      These novel observations of conspicuous intermyofibrillar lipid and progressive
      adipocyte replacement in dysferlin-deficient muscles present a new focus for
      investigating the mechanisms that result in the progressive decline of muscle
      function in dysferlinopathies. 

PMID- 24685691
TI  - On the substrate- and stereospecificity of the plant carotenoid cleavage
      dioxygenase 7.
AB  - Strigolactones are phytohormones synthesized from carotenoids via a
      stereospecific pathway involving the carotenoid cleavage dioxygenases 7 (CCD7)
      and 8. CCD7 cleaves 9-cis-beta-carotene to form a supposedly 9-cis-configured
      beta-apo-10'-carotenal. CCD8 converts this intermediate through a combination of
      yet undetermined reactions into the strigolactone-like compound carlactone. Here,
      we investigated the substrate and stereo-specificity of the Arabidopsis and pea
      CCD7 and determined the stereo-configuration of the beta-apo-10'-carotenal
      intermediate by using Nuclear Magnetic Resonance Spectroscopy. Our data
      unequivocally demonstrate the 9-cis-configuration of the intermediate. Both CCD7s
      cleave different 9-cis-carotenoids, yielding hydroxylated 9-cis-apo-10'
      carotenals that may lead to hydroxylated carlactones, but show highest affinity
      for 9-cis-beta-carotene. 

PMID- 24685692
TI  - The Clouston syndrome mutation connexin30 A88V leads to hyperproliferation of
      sebaceous glands and hearing impairments in mice.
AB  - Distinct mutations in the gap junction protein connexin30 (Cx30) can cause the
      ectodermal dysplasia Clouston syndrome in humans. We have generated a new mouse
      line expressing the Clouston syndrome mutation Cx30A88V under the control of the
      endogenous Cx30 promoter. Our results show that the mutated Cx30A88V protein is
      incorporated in gap junctional plaques of the epidermis. Homozygous Cx30A88V mice
      reveal hyperproliferative and enlarged sebaceous glands as well as a mild
      palmoplantar hyperkeratosis. Additionally, homozygous mutant mice show an altered
      hearing profile compared to control mice. We conclude that the Cx30A88V mutation
      triggers hyperproliferation in the skin and changes the cochlear homeostasis in
      mice. 

PMID- 24685693
TI  - Effects of PipX on NtcA-dependent promoters and characterization of the cox3
      promoter region in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120.
AB  - In Anabaena, the pipX gene is induced in the cells differentiating into
      heterocysts, being the PipX factor required for full expression of late
      heterocyst-specific genes. Here we show that PipX has a positive effect on in
      vitro binding of the transcription factor NtcA to DNA, as well as on transcript
      production, in different NtcA-dependent promoters. We found that the cox3 operon,
      encoding a heterocyst-specific terminal respiratory oxidase, is expressed from
      three nitrogen-regulated promoters to which NtcA binds. At the three sites, NtcA
      binding is potentiated by PipX. Thus, PipX has a direct effect on gene expression
      influencing the activity of NtcA. 

PMID- 24685694
TI  - miR-181a mediates metabolic shift in colon cancer cells via the PTEN/AKT pathway.
AB  - Cancer cell metabolism is often characterized by a shift from an oxidative to a
      glycolytic bioenergetics pathway, a phenomenon known as the warburg effect.
      Whether the deregulation of miRNAs contributes to the warburg effect remains
      largely unknown. Here we show that miR-181a expression is increased and thus
      induces a metabolic shift in colon cancer cells. miR-181a performs this function
      by inhibiting the expression of PTEN, leading to an increase of phosphorylated
      AKT which triggers metabolic shift. The increase of lactate production induced by
      miR-181a results in the rapid growth of cancer cells. These results identify miR
      181a as a molecular switch involved in the orchestration of the warburg effect in
      colon cancer cells via the PTEN/AKT pathway. 

PMID- 24685695
TI  - High expression of long non-coding RNA H19 is required for efficient
      tumorigenesis induced by Bcr-Abl oncogene.
AB  - Dysregulation of non-coding RNA H19 has been observed in various tumors. However,
      it remains unknown whether H19 is involved in Bcr-Abl-induced leukemia. Here, we
      demonstrate a critical requirement for H19 in Bcr-Abl-mediated tumorigenesis. H19
      was highly expressed in Bcr-Abl-transformed cell lines and primary cells derived
      from patients in a Bcr-Abl kinase-dependent manner. Silencing H19 expression
      sensitized leukemic cells to undergo imatinib-induced apoptosis and inhibited Bcr
      Abl-induced tumor growth. Furthermore, H19 was shown to be regulated by c-Myc in
      Bcr-Abl-expressing cells. These results reveal an important role H19 plays in Bcr
      Abl-mediated transformation and provide novel insights into complex mechanisms
      underlying Bcr-Abl-induced cancers. 

PMID- 24685696
TI  - Spermagglutinating Escherichia coli and its role in infertility: in vivo study.
AB  - PURPOSE: Association of Escherichia coli with its detrimental action on
      spermatozoa is well established in vitro. Therefore, an attempt was made to
      clarify the effect of presence of E. coli in Balb/c mouse vagina on fertility
      outcome. MATERIALS AND METHODS: All the mice in experimental groups received
      intravaginal administration of either spermagglutinating E. coli, PBS or standard
      E. coli strain (MTCC 1687; non-spermagglutinating/spermimmobilizing). Different
      doses and durations of administration were 10(4), 10(6), or 10(8) cfu for 10
      consecutive days; 10(4) or 10(6) for 3 consecutive days. Subgroups were created
      to evaluate cytokine level in reproductive organ and histopathological changes in
      both reproductive and non-reproductive organs. RESULTS: All the animals receiving
      either 10(4), 10(6) or 10(8) cfu of spermagglutinating E. coli for 3 or 10
      consecutive days were rendered infertile in contrast to groups receiving PBS or
      standard strain (MTCC 1687) of E. coli. Another group of mice receiving
      spermagglutinating E. coli when mated after the clearance of organism from mouse
      vagina under natural circumstances or with use of antibiotic remained fertile. No
      other clinical manifestation could be seen apparently or histologically, except
      minor rise in IL-10 level and mild leukocyte infiltration in vagina of animals
      inoculated with spermagglutinating E. coli. CONCLUSIONS: Our data suggests that
      presence of spermagglutinating strain of E. coli in vagina/vaginal tract might be
      playing significant role in fertility outcome.

PMID- 24685697
TI  - Role of intracellular events in the pathogenesis of dengue; an overview.
AB  - Dengue is one of the most important mosquito-borne viral diseases that are
      relentlessly spreading in newer areas in the tropical and subtropical regions of
      the World. In last fifty years, in spite of intensive and extensive
      investigations, pathogenesis of dengue is still not clearly understood. Recently,
      the research focus is on studying the role of intracellular events in
      pathogenesis of viral infections. Entry of virion in the host cell is followed by
      quick succession of events, unfolded protein response, lipid bodies and
      lipophagy, endoplasmic reticulum stress and recent demonstration of autophagy.
      The turbulence caused by these events may result in clearance of the
      virus/enhanced replication and survival of the host cell/apoptosis. Both,
      increased virus load and apoptosis of host cell may have pathological effects on
      the host. In the present review, we have summed up the role of various
      intracellular events in viral infections with special emphasis on Dengue virus
      infection. 

PMID- 24685698
TI  - Impact of Candida albicans hyphal wall protein 1 (HWP1) genotype on biofilm
      production and fungal susceptibility to microglial cells.
AB  - The hyphal wall protein 1 (HWP1) gene of Candida albicans encodes for a fungal
      cell wall protein, required for hyphal development and yeast adhesion to
      epithelial cells; yet, its role in pathogenesis remains largely unknown. In the
      present study, we analyzed two C. albicans laboratory strains, the DAY286
      (HWP1/HWP1) and the null mutant FJS24 (hwp1/hwp1) and six clinical isolates [3
      harbouring the homozygous HWP1 gene (HWP1/HWP1) and 3 the heterologous gene
      (HWP1/hwp1)]. Biofilm production, fungal HWP1 mRNA levels and ultrastructural
      morphology were investigated; also, the susceptibility of these strains to
      microglial cells was evaluated, in terms of fungal damage and immune cell
      mediated secretory response. When comparing the two laboratory strains, biofilm
      was produced to a similar extent independently on the genetic background, while
      the susceptibility to microglial cell-mediated damage was higher in the hwp1/hwp1
      mutant than in the HWP1/HWP1 counterpart. Also, transmission electron microscopy
      revealed differences between the two in terms of abundance in surface adhesin
      like structures, fungal cell wall shape and intracellular granules. When
      comparing the clinical isolates grouped according to their HWP1 genotype, reduced
      biofilm production and increased susceptibility to microglial cell-mediated
      damage occurred in the HWP1/hwp1 isolates with respect to the HWP1/HWP1
      counterparts; furthermore, upon exposure to microglial cells, the HWP1/HWP1
      isolates, but not the HWP1/hwp1 counterpart, showed enhanced HWP1 mRNA levels.
      Finally, both laboratory and clinical isolates exhibited reduced ability to
      stimulate TNFalpha and nitric oxide production by microglial cells in the case of
      heterozygous or null mutant HWP1 genotype. Overall, these data indicate that C.
      albicans HWP1 genotype influences pathogen morphological structure as well as its
      interaction with microglial cells, while fungal biofilm production results
      unaffected, thus arguing on its role as virulence factor that directly affects
      host mediated defences.

PMID- 24685699
TI  - Virulence properties, biofilm formation and random amplified polymorphic DNA
      analysis of Photobacterium damselae subsp. damselae isolates from cultured sea
      bream (Sparus aurata) and sea bass (Dicentrarchus labrax).
AB  - Photobacterium damselae subsp. damselae has been isolated from different
      outbreaks affecting cultured Sparus aurata and Dicentrarchus labrax. The aim of
      the present study was to characterize the phenotype and genotype of 12 P.
      damselae subsp. damselae strains isolated from these outbreaks. The roles of skin
      mucus in resistance to the initial infection steps have been studied. All tested
      strains resisted the bactericidal activity of the mucus and showed an ability to
      adhere to it, but only those showing hemolytic activity were found to be virulent
      by intraperitoneal injection. Phenotypic and genetic characterization revealed a
      considerable degree of variability within the subspecies. We found that RAPD-PCR
      represents a quick tool to generate information on intraspecific differences in
      environmental strains. We found, that some biotypes are more pathogenic than
      others, which by doing correlation between adhesion profile, enzymatic and
      hemolytic activity. 

PMID- 24685700
TI  - TLR4 in Toxoplasmosis; friends or foe?
AB  - Toxoplasma species are obligate intracellular protozoan which are responsible for
      induction of several forms of Toxoplasmosis in humans. The mechanisms responsible
      for the progression of the prolonged forms of Toxoplasmosis and associated
      pathologies are yet to be identified. However, previous studies proposed that
      immunological and genetic parameters may play important roles in the etiology and
      complexity of Toxoplasmosis. Pathogen recognition receptors (PRRs) recognize
      microbial antigens and induce immune responses against parasites, including
      toxoplasma species. Toll like receptors (TLRs) are PRRs which recognize
      toxoplasma as a pathogenic parasite and activate immune cells. It has been
      reported that the TLR4 is a critical innate immune cell receptor in toxoplasma
      detection and subsequently activates immune responses using either MYD88 or TRIF
      pathways. This review collates recent information regarding the role of TLR4 and
      its related signaling molecules with Toxoplasmosis.

PMID- 24685701
TI  - Environmental pH influences Candida albicans biofilms regarding its structure,
      virulence and susceptibility to fluconazole.
AB  - Candida albicans colonizes sites with different environmental pH. However, it is
      unclear how these conditions can interfere on biofilms. This study aimed to
      evaluate the influence of environmental pH on behavior of C. albicans regarding
      its structure, virulence and susceptibility to fluconazole (FLZ). Minimal
      inhibitory concentration, minimal fungicidal concentration and time kill were
      used to evaluate the susceptibility to FLZ in planktonic cells under three pH
      values (4.0, 5.5, 7.0). These pH values were used for biofilms analysis. C.
      albicans ATCC 90028 was developed on poly(methlymethacrylate) resin for 48 h.
      Then, 2.56 MUg/mL of FLZ was added to experimental groups for 24 h, and biofilms
      were analyzed by cell quantification, bioactivity, secretion of proteinases and
      phospholipases and structure. All data were analyzed by two-way ANOVA, followed
      by Tukey's test (alpha = 0.05). For planktonic cells, changes in environmental pH
      decreased the susceptibility to FLZ. C. albicans biofilms developed at pH 5.5
      showed higher cell counts, bioactivity, bio-volume, average thickness and
      roughness coefficient (p < 0.05). In contrast, the presence of FLZ at pH 4.0 did
      not influence the structural parameters (p > 0.05), but increased secretion of
      proteinase and phospholipase (p < 0.05). Within the conditions studied, it was
      shown that environmental pH modulates the structure, virulence and susceptibility
      of C. albicans to FLZ.

PMID- 24685702
TI  - Relaxation guided imagery reduces motor fluctuations in Parkinson's disease.
AB  - BACKGROUND: Motor fluctuations in Parkinson's disease (PD) cause major disabling
      symptoms. OBJECTIVE: We aimed to assess the efficacy of relaxation guided imagery
      in PD patients with motor fluctuation. METHODS: In a prospective pilot, case
      cohort, PD patients underwent (i) a relaxation session with relaxation guided
      imagery, and (ii) a control session of relaxing music. Three-day diaries were
      completed at baseline and after each intervention. Subsequently, patients
      received discs for home listening-a relaxation guided imagery disc and a relaxing
      music disc. After three months the patients were interviewed by phone. RESULTS:
      Twenty one PD patients participated and 19 completed this study. There was a
      significant increase in the percent of "on" time after listening to the
      relaxation guided imagery disc as compared with baseline (from 47.7% to 62.8%,
      95% CI 5.26-25.03, p = 0.005). Relaxing music caused no significant change in
      percent of "on" time from baseline (from 47.7% to 53.0%, p = 0.161). Although all
      sessions were performed in "on" state, there was a significant decrease in UPDRS
      motor subscores after each of the two sessions as compared with the UPDRS score
      before the session (relaxation guided imagery mean reduction -3.81 p = 0.0002 and
      after relaxing music mean reduction -1.95, p = 0.001), significantly more so
      after the relaxation guided imagery (p = 0.020). After 3 months listening to the
      relaxation guided imagery disc increased "on" time from baseline by 12.6% (95% CI
      3.19-28.39, p = 0.111) but this did not reach statistical significance.
      CONCLUSION: In this pilot study we showed that relaxation guided imagery is a
      promising treatment for PD.

PMID- 24685703
TI  - Synthesis, antinociceptive activity and pharmacokinetic profiles of nicorandil
      and its isomers.
AB  - Nicorandil (N-(2-hydroxyethyl)nicotinamide nitrate) is an antianginal drug, which
      activates guanylyl cyclase and opens the ATP-dependent K(+) channels, actions
      that have been suggested to mediate its vasodilator activity. We synthesized
      nicorandil and its two isomers, which vary in the positions of the side chain
      containing the nitric oxide (NO) donor, and also their corresponding denitrated
      metabolites. The activities of these compounds were evaluated in an experimental
      model of pain in mice. Pharmacokinetic parameters of nicorandil and its isomers,
      as well as the plasma concentrations of the corresponding denitrated metabolites
      and also nicotinamide and nitrite were determined. Nicorandil exhibited the
      highest antinociceptive activity, while the ortho-isomer was the least active.
      Nicorandil and para-nicorandil, which induced higher plasma concentrations of
      nitrite, exhibited higher antinociceptive activity, which suggests that the
      release of NO may mediate this activity. 

PMID- 24685704
TI  - Structure-activity relationships of pyrazole derivatives as potential
      therapeutics for immune thrombocytopenias.
AB  - Idiopathic or immune thrombocytopenia (ITP) is a serious clinical disorder
      involving the destruction of platelets by macrophages. Small molecule
      therapeutics are highly sought after to ease the burden on current therapies
      derived from human sources. Earlier, we discovered that dimers of five-membered
      heterocycles exhibited potential to inhibit phagocytosis of human RBCs by
      macrophages. Here, we reveal a structure-activity relationship of the bis
      pyrazole class of molecules with -C-C-, -C-N- and -C-O- linkers, and their
      evaluation as inhibitors of phagocytosis of antibody-opsonized human RBCs as
      potential therapeutics for ITP. We have uncovered three potential candidates, 37,
      47 and 50, all carrying a different linker connecting the two pyrazole moieties.
      Among these compounds, hydroxypyrazole derivative 50 is the most potent compound
      with an IC50 of 14 +/- 9 MUM for inhibiting the phagocytosis of antibody
      opsonized human RBCs by macrophages. None of the compounds exhibited significant
      potential to induce apoptosis in peripheral blood mononuclear cells (PBMCs).
      Current study has revealed specific functional features, such as up to 2-atom
      spacer arm and alkyl substitution at one of the N(1) positions of the bivalent
      pyrazole core to be important for the inhibitory activity.

PMID- 24685705
TI  - Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal
      targeting in mouse models of inflammatory bowel diseases.
AB  - The purpose of this study was to investigate the therapeutic potential of
      budesonide loaded nanocarriers for the treatment of inflammatory bowel disease
      (IBD). First, budesonide was encapsulated in poly(lactic-co-glycolic) acid (PLGA)
      nanoparticles by an oil in water (O/W) emulsion technique. A second batch of the
      same nanoparticles was additionally coated with a pH-sensitive methyl
      methacrylate-copolymer. The particle sizes of the plain and the coated PLGA were
      200+/-10.1nm and ~240+/-14.7nm, respectively. As could be shown in vitro, the pH
      sensitive coating prevented premature drug release at acidic pH and only releases
      the drug at neutral to slightly alkaline pH. The efficacy of both coated and
      plain nanoparticle formulations was assessed in different acute and chronic
      colitis mouse models, also in comparison to an aqueous solution of the drug. The
      dose was always the same (0.168mg/kg). It was found that delivery by coated PLGA
      nanoparticles alleviated the induced colitis significantly better than by plain
      PLGA particles, which was already more effective than treatment with the same
      dose of the free drug. These data further corroborate the potential of polymeric
      nanocarriers for targeted drug delivery to the inflamed intestinal mucosa, and
      that this concept can still be further improved regarding the oral route of
      administration by implementing pH-dependent drug release characteristics. 

PMID- 24685706
TI  - Targeting and depletion of circulating leukocytes and cancer cells by lipophilic
      antibody-modified erythrocytes.
AB  - There is a great interest in targeting and selective ablation of populations of
      circulating cells for research or therapeutic purposes. Red blood cells (RBCs)
      are readily available and fully biocompatible long-circulating intravascular
      carriers (natural life is 120days) that are amenable to chemical modifications,
      drug loading and reinjection. Here we demonstrate that using our previously
      described lipophilic ligand painting strategy, red blood cells (RBCs) could be in
      one step converted into targeted entities that selectively seek and bind various
      cells in vitro and in vivo. In vitro, RBCs modified with lipophilic anti-EpCAM or
      anti-CD45 antibodies efficiently bound to cancer cells and leukocytes, forming
      characteristic rosettes. In vivo, intravenously injected RBCs painted with anti
      CD45 antibody immediately associated with CD45 positive cells in blood, forming
      RBC-leukocyte rosettes. Moreover, anti-CD45-modified RBCs, but not the same
      amount of anti-CD45 antibody or anti-CD45-lipid conjugate (1-2MUg/mouse),
      depleted over 50% of CD45+ leukocytes from circulation, with main clearance
      organs of leukocytes being liver and spleen with no visible deposition in kidneys
      and lungs. Anti-CD20 (Rituximab)-painted RBCs efficiently (over 90%) depleted
      CD19+/CD20+/CD45+ human lymphoma cells in mantle cell lymphoma (MCL) JeKo-1
      model, while the same amount of rituximab-lipid (2MUg/mouse) was much less
      efficient in lymphoma cell depletion. Treatment of MCL mice with rituximab
      modified RBCs carrying only 2MUg of the antibody resulted in a significant
      prolongation of survival as compared to the same amount of antibody-lipid
      control. Lipophilic ligand-painted RBCs is a novel tool that can be utilized for
      targeting blood borne cells for experimental immunology and drug delivery
      applications. 

PMID- 24685707
TI  - A novel approach for noninvasive drug delivery and sensing through the amniotic
      sac.
AB  - Current invasive prenatal tests (amniocentesis and chorionic villus sampling) are
      known for their risk to the fetus. In the last decade, the use and awareness of
      these prenatal tests have increased, resulting in growing demand for a safe, non
      invasive, and accurate prenatal test. Chemical penetration enhancers (CPEs) have
      long been used to increase transport phenomena across skin and other membranes
      (e.g., tympanic membrane). The amniotic sac membrane is called the chorioamnion
      (CA) membrane and serves as the physical barrier between the fetus and the
      mother. In this research, the effect of CPEs on human CA mass transport was
      evaluated both in vitro and ex vivo. The results show that the tested CPEs
      exhibit an enhancing effect on CA mass transport. Based on the permeability
      results, two mechanisms of action were suggested: "extractors" and "fluidizers".
      Fourier transform infrared (FTIR) and rapid colorimetric screening measurements
      supported the mechanisms, based on which, more potent compounds were designed and
      tested for their enhancing effect. The enhancing mass transport effect of CPEs on
      CA membrane may be used both for sampling of cell-free DNA and for noninvasively
      administering drugs and other biological agents to the amniotic sac. 

PMID- 24685708
TI  - Clinician acceptance is the key factor for sustainable telehealth services.
AB  - Telehealth, the delivery of health care services at a distance using information
      and communications technology, has been slow to be adopted and difficult to
      sustain. Researchers developing theories concerning the introduction of complex
      change into health care usually take a multifactorial approach; we intentionally
      sought a single point of intervention that would have maximum impact on
      implementation. We conducted a qualitative interview study of 36 Australian
      telehealth services, sampled for maximum variation, and used grounded theory
      methods to develop a model from which we chose the most important factor
      affecting the success of telehealth. We propose that clinician acceptance
      explains much of the variation in the uptake, expansion, and sustainability of
      Australian telehealth services, and that clinician acceptance could, in most
      circumstances, overcome low demand, technology problems, workforce pressure, and
      lack of resourcing. We conclude that our model offers practical advice to those
      seeking to implement change with limited resources. 

PMID- 24685709
TI  - Chasing a moving target: outcome and risk stratification in patients with
      transposition of the great arteries after atrial switch operation.

PMID- 24685710
TI  - Using the electrocardiogram as a crystal ball for cardiovascular and all-cause
      mortality.

PMID- 24685711
TI  - Dual opposing roles of adaptive immunity in hypertension.
AB  - Hypertension involves remodelling and inflammation of the arterial wall.
      Interactions between vascular and inflammatory cells play a critical role in
      disease initiation and progression. T effector and regulatory lymphocytes,
      members of the adaptive immune system, play contrasting roles in hypertension.
      Signals from the central nervous system and the innate immune system antigen
      presenting cells activate T effector lymphocytes and promote their
      differentiation towards pro-inflammatory T helper (Th) 1 and Th17 phenotypes. Th1
      and Th17 effector cells, via production of pro-inflammatory mediators,
      participate in the low-grade inflammation that leads to blood pressure elevation
      and end-organ damage. T regulatory lymphocytes, on the other hand, counteract
      hypertensive effects by suppressing innate and adaptive immune responses. The
      present review summarizes and discusses the adaptive immune mechanisms that
      participate in the pathophysiology in hypertension. 

PMID- 24685713
TI  - Responsiveness to loop diuretics in heart failure.

PMID- 24685712
TI  - High-sensitivity cardiac troponin T and cognitive function and dementia risk: the
      atherosclerosis risk in communities study.
AB  - AIM: Clinical cardiovascular disease is a major risk factor for cognitive
      impairment and dementia. However, less is known about the association of
      subclinical myocardial damage with cognition and dementia. We sought to examine
      the associations of high-sensitivity cardiac troponin T (hs-cTnT) with cognition
      and dementia. METHODS AND RESULTS: Cross-sectional analysis of cognition
      (baseline 1996-98) and prospective analysis of dementia (follow-up through 2010)
      in 9472 participants in the Atherosclerosis Risk in Communities study. High
      sensitivity cardiac troponin T was measured using a novel highly sensitive assay
      with a lower limit of the blank of 3 ng/L. Cognitive function was assessed by
      three tests: the delayed word recall test (DWRT), the digit symbol substitution
      test (DSST), and the word fluency test (WFT). Dementia was defined using ICD-9
      codes. Linear regression and Cox models were adjusted for traditional
      cardiovascular risk factors. The mean age of participants was 63 years, 59% were
      female, 21% were black, and 66% had hs-cTnT >=3 ng/L. In cross-sectional
      analyses, higher hs-cTnT was associated with lower scores on the DSST (P-trend <
      0.001) and the WFT (P-trend = 0.002), but not on the DWRT (P-trend = 0.089). Over
      a median of 13 years, there were 455 incident dementia hospitalizations. In
      prospective analyses, higher baseline concentrations of hs-cTnT were associated
      with an increased risk for dementia hospitalizations overall (P-trend < 0.001)
      and for vascular dementia (P-trend = 0.029), but not for Alzheimer's dementia (P
      trend = 0.212). CONCLUSION: Elevations in baseline concentrations of hs-cTnT were
      associated with lower cognitive test scores at baseline and increased dementia
      hospitalization risk during the follow-up. Our results suggest that subclinical
      myocardial injury is associated with cognition and dementia.

PMID- 24685715
TI  - Temporal and intraclonal variation of flowering and pseudovivipary in Poa
      bulbosa.
AB  - BACKGROUND AND AIMS: Versatility in the reproductive development of
      pseudoviviparous grasses in response to growth conditions is an intriguing
      reproduction strategy. To better understand this strategy, this study examined
      variation in flowering and pseudovivipary among populations, co-occurring clones
      within populations, and among tillers in individual clones of Poa bulbosa, a
      summer-dormant geophytic grass that reproduces sexually by seed, and asexually by
      basal tiller bulbs and bulbils formed in proliferated panicles. METHODS: Clones
      were collected from 17 populations across a rainfall gradient. Patterns of
      reproduction were monitored for 11 years in a common garden experiment and
      related to interannual differences in climatic conditions. Intraclonal variation
      in flowering and pseudovivipary was studied in a phytotron, under daylengths
      marginal for flowering induction. KEY RESULTS: Clones showed large temporal
      variability in their reproductive behaviour. They flowered in some years but not
      in others, produced normal or proliferated panicles in different years, or became
      dormant without flowering. Proliferating clones did not show a distinct time
      sequence of flowering and proliferation across years. Populations differed in
      incidence of flowering and proliferation. The proportion of flowering clones
      increased with decreasing rainfall at the site of population origin, but no
      consistent relationship was found between flowering and precipitation in the
      common garden experiment across years. In contrast, flowering decreased at higher
      temperatures during early growth stages after bulb sprouting. Pulses of soil
      fertilization greatly increased the proportion of flowering clones and panicle
      production. High intraclonal tiller heterogeneity was observed, as shown by the
      divergent developmental fates of daughter plants arising from bulbs from the same
      parent clone and grown under similar conditions. Panicle proliferation was
      enhanced by non-inductive 8 h short days, while marginally inductive 12 h days
      promoted normal panicles. CONCLUSIONS: Interannual variation in flowering and
      proliferation in P. bulbosa clones was attributed to differences in the onset of
      the rainy season, resulting in different daylength and temperature conditions
      during the early stages of growth, during which induction of flowering and
      dormancy occurs.

PMID- 24685714
TI  - Arabinogalactan protein 31 (AGP31), a putative network-forming protein in
      Arabidopsis thaliana cell walls?
AB  - BACKGROUND AND AIMS: Arabinogalactan protein 31 (AGP31) is a remarkable plant
      cell-wall protein displaying a multi-domain organization unique in Arabidopsis
      thaliana: it comprises a predicted signal peptide (SP), a short AGP domain of
      seven amino acids, a His-stretch, a Pro-rich domain and a PAC (PRP-AGP containing
      Cys) domain. AGP31 displays different O-glycosylation patterns with
      arabinogalactans on the AGP domain and Hyp-O-Gal/Ara-rich motifs on the Pro-rich
      domain. AGP31 has been identified as an abundant protein in cell walls of
      etiolated hypocotyls, but its function has not been investigated thus far.
      Literature data suggest that AGP31 may interact with cell-wall components. The
      purpose of the present study was to identify AGP31 partners to gain new insight
      into its function in cell walls. METHODS: Nitrocellulose membranes were prepared
      by spotting different polysaccharides, which were either obtained commercially or
      extracted from cell walls of Arabidopsis thaliana and Brachypodium distachyon.
      After validation of the arrays, in vitro interaction assays were carried out by
      probing the membranes with purified native AGP31 or recombinant PAC-V5-6xHis. In
      addition, dynamic light scattering (DLS) analyses were carried out on an AGP31
      purified fraction. KEY RESULTS: It was demonstrated that AGP31 interacts through
      its PAC domain with galactans that are branches of rhamnogalacturonan I. This is
      the first experimental evidence that a PAC domain, also found as an entire
      protein or a domain of AGP31 homologues, can bind carbohydrates. AGP31 was also
      found to bind methylesterified polygalacturonic acid, possibly through its His
      stretch. Finally, AGP31 was able to interact with itself in vitro through its PAC
      domain. DLS data showed that AGP31 forms aggregates in solution, corroborating
      the hypothesis of an auto-assembly. CONCLUSIONS: These results allow the proposal
      of a model of interactions of AGP31 with different cell-wall components, in which
      AGP31 participates in complex supra-molecular scaffolds. Such scaffolds could
      contribute to the strengthening of cell walls of quickly growing organs such as
      etiolated hypocotyls.

PMID- 24685716
TI  - The effects of localized heating and disbudding on cambial reactivation and
      formation of earlywood vessels in seedlings of the deciduous ring-porous
      hardwood, Quercus serrata.
AB  - BACKGROUND AND AIMS: The networks of vessel elements play a vital role in the
      transport of water from roots to leaves, and the continuous formation of
      earlywood vessels is crucial for the growth of ring-porous hardwoods. The
      differentiation of earlywood vessels is controlled by external and internal
      factors. The present study was designed to identify the limiting factors in the
      induction of cambial reactivation and the differentiation of earlywood vessels,
      using localized heating and disbudding of dormant stems of seedlings of a
      deciduous ring-porous hardwood, Quercus serrata. METHODS: Localized heating was
      achieved by wrapping an electric heating ribbon around stems. Disbudding involved
      removal of all buds. Three treatments were initiated on 1 February 2012, namely
      heating, disbudding and a combination of heating and disbudding, with untreated
      dormant stems as controls. Cambial reactivation and differentiation of vessel
      elements were monitored by light and polarized-light microscopy, and the growth
      of buds was followed. KEY RESULTS: Cambial reactivation and differentiation of
      vessel elements occurred sooner in heated seedlings than in non-heated seedlings
      before bud break. The combination of heating and disbudding of seedlings also
      resulted in earlier cambial reactivation and differentiation of first vessel
      elements than in non-heated seedlings. A few narrow vessel elements were formed
      during heating after disbudding, while many large earlywood vessel elements were
      formed in heated seedlings with buds. CONCLUSIONS: The results suggested that, in
      seedlings of the deciduous ring-porous hardwood Quercus serrata, elevated
      temperature was a direct trigger for cambial reactivation and differentiation of
      first vessel elements. Bud growth was not essential for cambial reactivation and
      differentiation of first vessel elements, but might be important for the
      continuous formation of wide vessel elements.

PMID- 24685717
TI  - High-field ELDOR-detected NMR study of a nitroxide radical in disordered solids:
      towards characterization of heterogeneity of microenvironments in spin-labeled
      systems.
AB  - The combination of high-field EPR with site-directed spin-labeling (SDSL)
      techniques employing nitroxide radicals has turned out to be particularly
      powerful in probing the polarity and proticity characteristics of protein/matrix
      systems. This information is concluded from the principal components of the
      nitroxide Zeeman (g), nitrogen hyperfine (A) and quadrupole (P) tensors of the
      spin labels attached to specific sites. Recent multi-frequency high-field EPR
      studies underlined the complexity of the problem to treat the nitroxide
      microenvironment in proteins adequately due to inherent heterogeneities which
      result in several principal x-components of the nitroxide g-tensor. Concomitant,
      but distinctly different nitrogen hyperfine components could, however, not be
      determined from high-field cw EPR experiments owing to the large intrinsic EPR
      linewidth in fully protonated guest/host systems. It is shown in this work that,
      using the W-band (95GHz) ELDOR- (electron-electron double resonance) detected NMR
      (EDNMR) method, different principal nitrogen hyperfine, Azz, and quadrupole, Pzz,
      tensor values of a nitroxide radical in glassy 2-propanol matrix can be measured
      with high accuracy. They belong to nitroxides with different hydrogen-bond
      situations. The satisfactory resolution and superior sensitivity of EDNMR as
      compared to the standard ENDOR (electron-nuclear double resonance) method are
      demonstrated. 

PMID- 24685718
TI  - Synergizing immunotherapy with molecular-targeted anticancer treatment.
AB  - The therapeutic opportunity for anticancer kinase inhibitors (KIs) that block
      cell-signaling pathways is materializing. Yet, these molecular-targeted therapies
      are not tailored to be allies of the immune system, and often antagonize it
      despite generating antigenic activity. KIs usually offer an incomplete cure and
      one culprit is the lack of synergy between the drug and the immune system, a
      problem that is magnified when the therapeutic context involves HIV-1-induced
      immunosuppression (AIDS). We outline a strategy to fulfill the therapeutic
      imperative of recruiting cooperative immune responses. Accordingly, we propose a
      method to redesign anticancer drugs to harness the antigenic products of drug
      induced apoptosis of tumor cells, thus eliciting an adjuvant immune response. 

PMID- 24685719
TI  - Effect of Laser wavelength on delivering appropriate laser burns through the
      opaque lens using a pattern scan laser.
AB  - BACKGROUND/AIMS: We evaluated the effects of pattern scan laser (PSL) wavelength
      in delivering appropriate laser burns to the retina of eyes with an opaque lens.
      METHODS: Sixteen shots of 2 * 2 square grids (64 laser spots) were delivered
      using green (532-nm), yellow (577-nm) and red (647-nm) lasers to the retinas of
      mice with mild cataract induced by chloral hydrate (400 mg/kg). Three eyes with
      clear lenses served as controls. One week after laser coagulation, the ratio of
      appropriate burns, defined as coagulation restricted to the outer half of the
      retina without retinal or choroidal hemorrhage, was investigated histologically.
      RESULTS: With the green laser, we confirmed only 3.0 +/- 2.0 appropriate burns in
      eyes with an opaque lens, in contrast to 13.7 +/- 4.0 effective burns in eyes
      with a clear lens. On the other hand, the yellow and red lasers produced 18 +/-
      5.2 and 13 +/- 1.5 appropriate burns, respectively, in eyes with an opaque lens.
      CONCLUSION: Although all three PSL wavelengths successfully delivered appropriate
      burns restricted to the outer half of the retina in eyes with an opaque lens, the
      longer-wavelength yellow and red lasers were significantly more effective than
      the green laser. PSL may be a treatment option to accompany anti-vascular
      endothelial growth factor drug therapy.

PMID- 24685720
TI  - High penetrance of a pan-canina type rDNA family in intersection Rosa hybrids
      suggests strong selection of bivalent chromosomes in the section Caninae.
AB  - All dogroses (Rosa sect. Caninae) are characterized by the peculiar canina
      meiosis in which genetic material is unevenly distributed between female and male
      gametes. The pan-canina rDNA family (termed beta) appears to be conserved in all
      dogroses analyzed so far. Here, we have studied rDNAs in experimental hybrids
      obtained from open pollination of F1 plants derived from 2 independent
      intersectional crosses between the pentaploid dogrose species (2n = 5x = 35) Rosa
      rubiginosa as female parent (producing 4x egg cells due to the unique
      asymmetrical canina meiosis) and the tetraploid (2n = 4x = 28) garden rose R.
      hybrida 'Andre Brichet' as male parent (producing 2x pollen after normal
      meiosis). We analyzed the structure of rDNA units by molecular methods [CAPS and
      extensive sequencing of internal transcribed spacers (ITS)] and determined the
      number of loci on chromosomes by FISH. FISH showed that R. rubiginosa and 'Andre
      Brichet' harbored 5 and 4 highly heteromorphic rDNA loci, respectively. In the
      second generation of hybrid lines, we observed a reduced number of loci (4 and 5
      instead of the expected 6). In R. rubiginosa and 'Andre Brichet', 2-3 major ITS
      types were found which is consistent with a weak homogenization pressure
      maintaining high diversity of ITS types in this genus. In contrast to expectation
      (the null hypothesis of Mendelian inheritance of ITS families), we observed
      reduced ITS diversity in some individuals of the second generation which might
      derive from self-fertilization or from a backcross to R. rubiginosa. In these
      individuals, the pan-canina beta family appeared to be markedly enriched, while
      the paternal families were lost or diminished in copies. Although the mechanism
      of biased meiotic transmission of certain rDNA types is currently unknown, we
      speculate that the bivalent-forming chromosomes carrying the beta rDNA family
      exhibit extraordinary pairing efficiency and/or are subjected to strong selection
      in Caninae polyploids.

PMID- 24685722
TI  - Reply: A network meta-analysis of the efficacy of opioid analgesics for the
      management of breakthrough cancer pain episodes.

PMID- 24685721
TI  - Monocytes activate natural killer cells via inflammasome-induced interleukin 18
      in response to hepatitis C virus replication.
AB  - BACKGROUND & AIMS: Production of interferon (IFN)-gamma by natural killer (NK)
      cells is attenuated during chronic infection with hepatitis C virus (HCV). We
      investigated whether this is due to intrinsic or extrinsic mechanisms of NK
      cells. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from
      patients with chronic HCV infection or uninfected blood donors (controls); NK
      cells and monocytes were isolated or eliminated. We cultured hepatoma cells that
      express luciferase-tagged subgenomic HCV replicons (Huh7/HCV replicon cells) or
      their HCV-negative counterparts (Huh7) with NK cells in the presence or absence
      of other populations of PBMCs. Antiviral activity, cytotoxicity, and cytokine
      production were assessed. RESULTS: NK cells produced greater amounts of IFN-gamma
      when PBMC were cocultured with Huh7/HCV replicon cells than with Huh7 cells; NK
      cells and PBMCs from controls suppressed HCV replication to a greater extent than
      those from patients with chronic HCV infection. This antiviral effect was
      predominantly mediated by tumor necrosis factor (TNF)-alpha and IFN-gamma. The
      antiviral activity of NK cells and their production of IFN-gamma were reduced
      when they were used in coculture alone (rather than with PBMC), or after
      depletion of CD14(+) monocytes, after knockdown of the inflammasome in monocytes,
      or after neutralization of interleukin-18, which is regulated by the
      inflammasome. These findings indicate a role for monocytes in NK cell activation.
      Compared with control monocytes, monocytes from patients with chronic HCV
      infection had reduced TNF-alpha-mediated (direct) and reduced NK cell-mediated
      (indirect) antiviral effects. Control monocytes increased the antiviral effects
      of NK cells from patients with chronic HCV infection and their production of IFN
      gamma. CONCLUSIONS: Monocytes sense cells that contain replicating HCV and
      respond by producing interleukin-18 via the inflammasome and by activating NK
      cells. Patients with chronic HCV infection have reduced monocyte function,
      attenuating NK cell IFN-gamma-mediated responses.

PMID- 24685723
TI  - A prospective study to investigate contributory factors that lead to constipation
      in palliative care patients.

PMID- 24685724
TI  - A randomized crossover clinical trial to evaluate the efficacy of oral
      transmucosal fentanyl citrate in the treatment of dyspnea on exertion in patients
      with advanced cancer.

PMID- 24685725
TI  - The first confirmed case of human avian influenza A(H7N9) in Hong Kong and the
      suspension of volunteer services: impact on palliative care.

PMID- 24685726
TI  - Simultaneous determination of bosentan and glimepiride in human plasma by ultra
      performance liquid chromatography tandem mass spectrometry and its application to
      a pharmacokinetic study.
AB  - A sensitive and rapid ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS) method was developed to determine bosentan (BOS) and
      glimepiride (GPD) in human plasma simultaneously. Chromatographic separation was
      carried out on an Acquity UPLC BEH C18 column and mass spectrometric analysis was
      performed using a QTrap5500 mass spectrometer coupled with an electro-spray
      ionization (ESI) source in the positive ion mode. The MRM transitions of m/z
      552.0->202.1 and m/z 491.2->125.9 were used to quantify BOS and GPD,
      respectively. This assay method has been fully validated in terms of selectivity,
      linearity, recovery and matrix effect, accuracy, precision and stability. The
      linearity of this method was found to be within the concentration range of 5-1000
      ng/mL for BOS, and 2.5-500 ng/mL for GPD in human plasma. Only 1.5 min was needed
      for an analytical run. This assay was used to support a clinical study where
      multiple oral doses were administered to healthy Chinese subjects to investigate
      the pharmacokinetics of BOS and GPD.

PMID- 24685727
TI  - Tissue-smashing based ultra-rapid extraction of chemical constituents in herbal
      medicines.
AB  - Sample extraction is the first challenge in analysis of herbal medicines (HMs).
      Numerous methods have been developed to improve extraction efficiency, use less
      solvent and short time. In this work, a tissue-smashing based ultra-rapid
      extraction (TSURE) method has been proposed through the designed particle
      crushing, drastic stir, and dynamic molecular permeation at normal temperature.
      Factors in TSURE like extraction time, volts, and solvents were optimized for
      extraction efficiency of salvianolic acid B, cryptotanshinone, and tanshinone IIA
      from Salvia miltiorrhiza. The TSURE method was validated in terms of
      repeatability (RSD<2.2%) and extraction recoveries (93-106% with RSD<5.0%). TSURE
      showed a comparable extraction efficiency to conventional heat reflux extraction
      (HRE) and better than ultrasonic assisted extraction (UAE). The extraction time
      was about 2.0-3.0 min for TSURE, 60 times faster than the performance of HRE and
      20 times faster than UAE. Microscopic analysis showed that the Krummbein diameter
      of plant particles after extraction were about 600-1200 MUm for HRE and UAE, and
      decreased to 50-80 MUm for TSURE. Subsequently, the developed TSURE was applied
      to high-throughput extraction of 19 S. miltiorrhiza samples collected in
      different regions of China. Besides, application of TSURE to other herbal
      medicines was also investigated, including Panax quinquefolius and Lonicera
      japonica. TSURE method provided an ultra-rapid and promising alternation for
      extraction of ingredients in herbal medicines, and can be extended to
      pharmaceutics, foods and cosmetics.

PMID- 24685728
TI  - Surgery for juvenile nasopharyngeal angiofibroma with lateral extension to the
      infratemporal fossa.
AB  - OBJECTIVE: The study aimed to assess the usefulness of skull base surgery for
      large juvenile nasopharyngeal angiofibroma (JNA) with lateral extension to the
      infratemporal fossa. MATERIALS AND METHODS: Eleven cases were enrolled for this
      study, and the mean age was 17.7 years old (range: 8-32). Six out of 11 cases
      underwent surgery as an initial treatment, and the other five underwent secondary
      surgery after initial surgery or radiotherapy in other institutions. The range of
      extension of tumor, feeding arteries, surgical approach, and treatment outcome
      were estimated. RESULTS: All tumors originated from the sphenopalatine foramen.
      Based on the imaging study, there was extension to the cavernous sinus observed
      in eight cases, as well as to the middle cranial fossa (8), orbit (4), and
      anterior cranial fossa (1). These tumors were diagnosed as Andrews' Stage IVa (3)
      and IVb (8). However, infiltration into the cavernous sinus was observed in one
      case only during surgery. Ten tumors were separated carefully from the cavernous
      sinus or dura and were accurately diagnosed as Stage IIIb. In all cases, the main
      arterial feeders of the JNAs were branches of the external carotid artery, which
      were embolized prior to surgery. However, 10 cases were also fed by branches of
      the internal carotid artery (branches of the ophthalmic artery), in which these
      arteries could not be embolized. Coronal skin incision (1) and a facial
      dismasking flap (9) were used, and in one case, wide lateral skin incision with
      temporary incision of the facial nerve was applied. The orbito-zygomatic approach
      and its modification was applied to all the cases. Fronto-lateral craniotomy was
      applied in four cases and lateral craniotomy in seven cases. Total resection was
      achieved in 10 cases and subtotal resection in one case. No mortality was noted
      in this series. Temporal trismus was observed in all cases which subsided
      gradually. Cheek numbness and facial palsy were observed in three and two cases,
      respectively. CONCLUSION: Coupled with craniotomy, tumor removal was successfully
      carried out in 11 patients with JNAs, which showed large lateral extension. Our
      surgical strategy is a safe and effective approach for the removal of JNAs with
      infratemporal fossa extension.

PMID- 24685729
TI  - Chronic kidney disease and the aging population.

PMID- 24685730
TI  - Chronic antibody-mediated rejection: review of literature.
AB  - Chronic antibody-mediated rejection among kidney transplant recipients is a major
      unresolved problem which is covered in this review article which included
      different lines of its management. 

PMID- 24685731
TI  - Coexistent renal milk of calcium and amyloidosis.

PMID- 24685732
TI  - Serum procalcitonin level for prediction of high-grade vesicoureteral reflux in
      urinary tract infection.
AB  - INTRODUCTION: Procalcitonin is a reliable and specific marker of bacterial
      infections such as urinary tract infection. Some authors suggest measurement of
      serum procalcitonin as a predictor of vesicoureteral reflux (VUR). We
      investigated this association in children admitted because of acute
      pyelonephritis. MATERIALS AND METHODS: Forty-eight children with the first
      febrile urinary tract infection were included. Twelve patients had low-grade VUR,
      9 patients had high-grade VUR, and 27 patients did not have any VUR in their
      imaging assessment. RESULTS: There was a significant association between high
      grade VUR and higher levels of procalcitonin (P = .04). The sensitivity of a
      procalcitonin level of 0.31 ng/mL or greater was 90% and the specificity was 32%
      for diagnosis of high-grade VUR. CONCLUSIONS: We concluded that serum
      procalcitonin concentration is a sensitive and promising predictor of high-grade
      VUR.

PMID- 24685733
TI  - Prevalence of chronic kidney disease and its contributing risk factors in
      southern Iran: a cross-sectional adult population-based study.
AB  - INTRODUCTION: The global prevalence of chronic kidney disease (CKD) is increasing
      consistently. Progression of CKD to end-stage renal disease could be slowed down
      by early detection and treatment, yet CKD and its risk factors have been poorly
      studied in many countries. This study investigated the CKD prevalence and its
      contributing risk factors in adult population of Southern Iran. MATERIALS AND
      METHODS: In this cross-sectional study on randomly recruited participants from
      adult population, we investigated the CKD prevalence (stages 3 to 5) and its risk
      factors in Southern Iran. After calculation of sample size (10385 cases), data
      was collected in a total of 10397 individuals. Medical and demographic data was
      obtained, as well as measurement of height, body weight, blood pressure, and
      blood urea nitrogen, and serum creatinine. A fresh spot urinalysis was also
      performed. RESULTS: The overall prevalence of CKD stages 3 to 5 was 11.6%. Stages
      1, 2, 3, 4, and 5 of CKD were found in 8.5%, 66.1%, 11.4%, 0.1%, and 0.1% of the
      participants, respectively. The prevalence of CKD (stages 3 to 5) was
      significantly higher compared to those with the non-CKD group, in the older than
      younger participants, and in the women as compared to the men. There was a strong
      positive correlation between age, female sex, hypertension, and high body mass
      index with different stages of CKD. CONCLUSIONS: The prevalence of CKD is high in
      Southern Iran and its contributing risk factors are older age, female sex,
      hypertension, and high body mass index.

PMID- 24685734
TI  - Relationship between kidney length and cortical thickness and circadian blood
      pressure measurements in hypertensive patients.
AB  - INTRODUCTION: It has been demonstrated that kidney length is associated with
      office blood pressure (BP) measurements. Several studies support that ambulatory
      BP measurements in comparison to conventional BP better correlate with
      hypertensive target organ damage, and that the lack of nocturnal dip in BP
      (nondipping) is related to an increase in the incidence of cardiovascular event
      in essential hypertensive patients. This study evaluated the specific
      relationship between kidney length, renal cortical thickness (RCT), and circadian
      BP in hypertensive patients. MATERIALS AND METHODS: In a cross-sectional study,
      144 patients with newly diagnosed essential hypertension underwent physical
      examination, office BP measurements, laboratory analysis, ambulatory BP
      monitoring, renal ultrasonography, and spot and 24-hour urine collection.
      RESULTS: There were 103 dipper (71.5%) and 41(28.5%) nondipper patients. Among
      the dippers, 13 were extreme dippers and among nondippers 11 were reverse
      dippers. Most of the ambulatory BP measurements were not associated with kidney
      length or RCT. Kidney length and RCT were not different among dippers, extreme
      dippers, nondippers, and reverse dippers. The kidney length and RCT were not
      different between patients with white coat hypertension and sustained
      hypertension, either. Logistic regression analysis did not show any independent
      association between kidney length, RCT, and nondipping status. CONCLUSIONS:
      Kidney length and RCT may not be associated with circadian BP monitoring.

PMID- 24685735
TI  - Clinical application of long-term Palindrome catheter in hemodialysis patients.
AB  - INTRODUCTION: This study was conducted to compare catheter function, dialysis
      adequacy, and dialysis-related complications among patients receiving long-term
      dialysis via Palindrome catheter, Permcath catheter, and arteriovenous fistula
      (AVF) as vascular access. MATERIALS AND METHODS: Forty-three patients undergoing
      dialysis with Permcath catheter, 49 with Palindrome catheter, and 56 with AVF
      were recruited. Urea clearance (KT/V), urea reduction rate, and the highest blood
      flow at the arteriovenous junction during dialysis were determined during the
      dialysis sessions. Catheter-related infection, catheter-associated thrombosis,
      and annual patency rate were also evaluated. RESULTS: In patients using Permcath
      catheter for dialysis, the incidence of secondary renal injury (metabolic
      diseases, hypertension, and ischemic kidney diseases) was 73.1%, which was
      significantly higher than that in patients with AVF (51.5%; P = .001). In the
      Palindrome group, maximum blood flow, KT/V, urea reduction rate, and annual
      patency rate were significantly higher than those in the Permcath group, and the
      incidence of access-related infection was significantly higher than that in the
      AVF group. In the Palindrome group, the prevalence of thromboembolism was 30.6%,
      which was significantly lower than that in the Permcath group (46.5%), but higher
      than that in the AVF group (5.4%). CONCLUSIONS: For dialysis patients, Palindrome
      catheter was superior to Permcath catheter and comparable with the AVF in terms
      of the maximum blood flow, dialysis adequacy, and annual patency rate. Dialysis
      with Palindrome catheter has a high infection rate and a high incidence of
      thromboembolism as in the dialysis with Permcath catheter.

PMID- 24685736
TI  - Dynamic changes of regulatory T cell and dendritic cell subsets in stable kidney
      transplant patients: a prospective analysis.
AB  - INTRODUCTION: We aimed to identify immune status of the stable kidney allografts
      from the point of some cellular changes that may occur after transplantation.
      MATERIALS AND METHODS: This study considered 57 patients with no rejection during
      the 6 months after transplantation. Flow cytometric frequencies of circulatory
      CD4+CD25+FoxP3+ and CD8+CD28- regulatory T cells (Treg) as well as myeloid
      dendritic cells type 1 (MDC1) and type 2 (MDC2) and plasmacytoid dendritic cells
      (PDC) were measured before transplantation and 2 weeks and 1, 3, and 6 months
      after transplantation. Using adjusted model of repeated measure analysis, we
      assessed the influence of different parameters on different cell subsets.
      RESULTS: The mean number of Tregs and PDCs decreased 2 weeks after
      transplantation and then increased as they reached their values before
      transplantation within a few months after transplantation. The mean MDC1s
      increased during 2 weeks and then decreased to its before-transplantation values
      within 6 months. The frequency of Tregs (r = 0.90) and MDC1s (r = 0.75) at month
      3 could strongly predict their frequencies at month 6. Different variables
      including family relationship between donor and recipient, glomerular filtration
      rate, and human leukocyte antigen antibody mismatch did not change the frequency
      of different cell subsets during the time. CONCLUSIONS: The dynamism and
      circulatory changes in the frequency of Tregs and PDCs are opposite to MDCs after
      kidney transplantation. We describe these changes in a group of patients with
      stable graft; however, our study does not render any idea in patients with
      unstable or rejecting grafts.

PMID- 24685737
TI  - Effect of applying continuous care model on quality of life among kidney
      transplant patients: a randomized clinical trial.
AB  - INTRODUCTION: The aim of this study was to compare the effect of continuous care
      model with routine care on the quality of life among patients who receive a
      kidney transplant. MATERIALS AND METHODS: In a randomized clinical trial, 90
      kidney transplant patients were selected from 4 hospitals in Tehran, Iran, and
      were randomly assigned to 2 group. In the experimental group, continuous care
      model was applied for 3 months and the control group received routine care. The
      scale scores of the Kidney Transplant Questionnaire concerning quality of life
      were monthly compared between the two groups. RESULTS: Of 90 patients, 4 in the
      experimental and 8 in the control group were excluded from the study. Final
      analysis was performed on 41 in the experimental and 37 in the control groups. No
      significant difference was found between the two groups in terms of demographic
      variables. Although the quality of life scores increased in both groups, the mean
      scores of the experimental group were significantly higher than those in the
      control group at 1, 2, and 3 months. CONCLUSIONS: Continuous care model may
      improve the kidney transplant patients' quality of life.

PMID- 24685738
TI  - Prospective study of BK virus infection and nephropathy during the first year
      after kidney transplantation.
AB  - INTRODUCTION: The aim of this study was to assess the prevalence and severity of
      BK virus infection, BK virus nephritis, and related risk factors among kidney
      transplant recipients. MATERIALS AND METHODS: BK viremia during the first year of
      kidney transplantation was assessed prospectively in 32 successive recipients. BK
      virus DNA was extracted and determined in all samples by real-time polymerase
      reaction assay for 1 year after kidney transplantation. RESULTS: The mean age of
      the patients was 33.3 +/- 15.3 years. Sixteen patients (50%) received
      antithymocyte globulin for induction therapy. Living donor transplant consisted
      of 75% of the kidney donations. Maintenance immunosuppressive therapy included
      cyclosporine A in 27 patients (84.4%), plus tapering prednisolone and
      mycophenolate mofetil. BK viremia was detected in 8 patients (25%). The highest
      detected plasma viral load was less than 4000 copies per milliliter. BK virus was
      respectively positive in 5 (62.5%), 2 (25%), and 1 (12.5%) patients during the
      first 4, 8, and 12 months after transplantation. Biopsy-proven rejection and
      antirejection therapy by methylprednisolone pulses were 5 and 2.3 times more
      common in patients with BK virus infection (P = .01 and P = .01), respectively.
      CONCLUSIONS: Despite occurrence of BK virus infection in 25% of our patients, BK
      nephropathy did not develop in any of them. Routine screening of BK virus
      infection, particularly in centers with low prevalence of BK virus nephritis, may
      not be cost effective for predicting this disease.

PMID- 24685739
TI  - Association of serum uric acid with level of blood pressure in type 2 diabetic
      patients.
AB  - This study was conducted to investigate the association between serum uric acid
      level and blood pressure in type 2 diabetes mellitus. Sixty patients with type 2
      diabetes mellitus were enrolled to the study. None of the patients had a history
      of gout, were treated with allopurinol, or were treated with antihypertensive
      drugs previously. The mean duration of DM was 9.2 +/- 4.9 years. The mean serum
      creatinine level was 0.98 +/- 0.22 mg/dL, and the mean serum UA level was 4.4 +/-
      1.2 mg/dL. The mean protein level in 24-hour urine sample was 388 +/- 22 mg/d.
      The mean systolic and diastolic blood pressure values were 133.0 +/- 13.0 mm Hg
      and 84.0 +/- 7.4 mm Hg, respectively. There was no significant difference in
      levels of serum uric acid, hemoglobin A1c, serum creatinine, proteinuria, or
      systolic and diastolic pressure between the men and the women. A significant
      positive correlation was seen between serum UA and systolic (r = 0.312, P = .02)
      and diastolic blood pressure (r = 0.297, P = .03). Results of this study suggest
      that serum uric acid had a strong association with levels of systolic and
      diastolic blood pressure in type 2 diabetic patients. More attention to the serum
      uric acid level and treatment of hyperuricemia could halt the progress of
      diabetic nephropathy.

PMID- 24685740
TI  - Urinary tract infection due to salmonella in an otherwise healthy child.
AB  - Salmonella species are a rare cause of urinary tract infection in children. They
      are associated with a high incidence of structural abnormalities or
      immunosuppressive status. We report the case of a healthy 7-year-old boy with
      pyelonephritis due to Salmonella group. He did not have a history of recent
      gastroenteritis. 

PMID- 24685741
TI  - Re: effects of low-glucose degradation product solution on peritoneal membrane
      characteristics in peritoneal dialysis patients: a 3-year follow-up study.

PMID- 24685742
TI  - Protective effect of hepatitis B virus-active antiretroviral therapy against
      primary hepatitis B virus infection.
AB  - OBJECTIVE: Current guidelines advise to vaccinate every hepatitis B virus (HBV)
      susceptible HIV patient against HBV until sufficient antibody titers have been
      reached. However, in this era of combination antiretroviral therapy (cART), acute
      HBV infection rarely occurs in patients who lack this immune protection. We
      analyzed whether HBV-active cART (lamivudine, emtricitabine, tenofovir) might
      work as a preexposure prophylaxis (PrEP) to explain this effect. METHODS: From
      our HIV cohort at the Onze Lieve Vrouwe Gasthuis hospital (N=2942), patients were
      selected retrospectively for negative HBV serology (HBsAg, anti-HBs and anti-HBc
      negative) at cohort entry. Men who have sex with men (MSM) with a second HBV
      serology available were included for analysis. The incidence of anti-HBc
      conversion was determined and correlated with the use of HBV-active drugs. Kaplan
      Meier curves and log-rank tests were used to compare HBV-free survival for MSM.
      RESULTS: In total, 33 HBV infections occurred in 381 eligible MSM over a median
      follow-up of 2470 days (interquartile range 1146-3871.5). The incident rate per
      100 patient-years of follow-up was 1.10 overall, but differed strongly dependent
      on the use of HBV-active drugs: 2.85/100 patient-years of follow-up in the
      absence of HBV-active drugs, 1.36 when only lamivudine was used, and 0.14 in the
      presence of tenofovir. Furthermore, HBV-free survival rate was significantly
      higher when HBV-active cART was used, in particular when this HBV-active cART
      contained tenofovir (log-rank P<0.001). CONCLUSION: Our findings demonstrate that
      HBV-active cART protects against the occurrence of de-novo HBV infection, most
      strongly when tenofovir is used.

PMID- 24685743
TI  - The protective effect of HIV-2 infection: implications for understanding HIV-1
      immunity.

PMID- 24685744
TI  - Persistent HIV infection in newborns: how soon is soon enough?

PMID- 24685745
TI  - Massive hypereosinophilia and vasculitis associated with major expansion of
      interleukin-5-producing CD8+ T cells in HIV-1 infection.

PMID- 24685746
TI  - Drug reaction with eosinophilia and systemic symptoms associated with raltegravir
      use: case report and review of the literature.

PMID- 24685747
TI  - Reactivation of hepatitis B virus infection associated with maraviroc use in an
      HIV-infected patient.

PMID- 24685749
TI  - Receiving the baton.

PMID- 24685748
TI  - Candidate chromosome 1 disease susceptibility genes for Sjogren's syndrome
      xerostomia are narrowed by novel NOD.B10 congenic mice.
AB  - Sjogren's syndrome (SS) is characterized by salivary gland leukocytic infiltrates
      and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1
      within the span of the Aec2 region. In an attempt to demonstrate that COX-2
      drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox
      2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking
      genes failed manifest xerostomia. Further backcrossing yielded disease
      susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that
      critical Aec2 genes lie within a 1.56 to 2.17Mb span of DNA downstream of Cox-2.
      Bioinformatics analysis revealed that susceptible and non-susceptible lines
      exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region,
      thereby better delineating candidate Aec2 alleles needed for SS xerostomia. 

PMID- 24685753
TI  - Put a stop to bullying new nurses.

PMID- 24685751
TI  - Palliative wound care, part 2: application of principles.
AB  - In part 1 of this 2-part series, we discussed principles of palliative care to
      help understand the goals of treatment in developing a plan of care. This
      article, Part 2, aims to provide knowledge of practical topical wound management
      by common wound etiologies and symptoms among persons who would benefit from
      palliative wound care. 

PMID- 24685754
TI  - Panic attacks.

PMID- 24685755
TI  - Bedbugs: what nurses need to know from treating lesions to treating the home,
      management of an infestation is multifaceted.
AB  - I t could happen to anyone. A family is vacationing, and after checking into a
      hotel the kids and their mother go to bed. A short while later, the husband
      approaches the bed where his wife is sleeping; he notices something moving on the
      white sheet near her head. It's an insect. He catches it, places it on a tissue,
      and logs onto his computer to try to identify it. Soon he realizes it's a bedbug,
      wakes his wife and children, and calls the front desk. The hotel's pest manager
      comes up and confirms it: there's a bedbug infestation in the room, and the hotel
      moves the family to another part of the building. 

PMID- 24685756
TI  - "Drink at least 8 glasses of water a day to be healthy???".
AB  - The saying "drink at least 8 glasses of water per day to be healthy" has had
      little supporting evidence. The purpose of this article was to briefly introduce
      the role of hydration in health in order to explore in more detail recent
      observational studies of hyperhydration in chronic kidney disease (CKD) in man.
      The Modification of Diet in Renal Disease study initially noted a negative
      association between increasing urine output and progression of CKD that was
      absent when corrected for baseline variables. Recently, data from 2 different
      cross-sectional populations found those with the highest fluid intake had a
      significantly lower risk of CKD. In a longitudinal, community-based cohort study
      adjusted for baseline variables, decline in kidney function was significantly
      slower in those with higher versus lower baseline urine volume. These new and
      contradictory results underline the need for a randomized controlled study to
      test the hypothesis that increased fluid intake will slow renal decline.

PMID- 24685757
TI  - Human trafficking: crime in our own backyard.
AB  - Imagine for a moment being in a small, cold, dark, and dirty room. You haven't
      seen your family in months and you're not sure if you ever will again. When the
      drugs that you've given begin to wear off, you feel hunger pangs because you
      haven't eaten anything in more hours than you can count. You hear a door opening
      and are filled with paralyzing fear and dread. You are never quite sure who or
      what will greet you on the other side of that door. You may have to endure a
      brutal beating, you may be forced to take drugs, or you may be raped. 

PMID- 24685758
TI  - Teaching patients with an intellectual disability.

PMID- 24685759
TI  - Meals on wheels.

PMID- 24685760
TI  - What's in a name?

PMID- 24685761
TI  - Making patients feel safe and valued.

PMID- 24685762
TI  - ABCA1 rs1883025 polymorphism shows no association with neovascular age-related
      macular degeneration or polypoidal choroidal vasculopathy in a Northern Chinese
      population.
AB  - PURPOSE: To analyze the association between ABCA1 rs1883025 variants with
      neovascular age-related macular degeneration (nAMD) and polypoidal choroidal
      vasculopathy (PCV) in a northern Chinese population. METHODS: The study enrolled
      900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV.
      Genomic DNA was extracted from venous blood leukocytes. Single-nucleotide
      polymorphisms in the ABCA1 (rs1883025) gene were genotyped by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. RESULTS: The ABCA1
      rs1883025 polymorphism was not significantly associated with nAMD (22.5%; p >
      0.05) or PCV (20.8%; p > 0.05) in a northern Chinese population. The association
      remained insignificant after adjustment for age and gender differences (p >
      0.05). CONCLUSIONS: This study suggests that ABCA1 rs1883025 variants are not
      associated with nAMD or PCV in a Chinese population, which is likely due to an
      ethnic difference.

PMID- 24685763
TI  - Surgency and negative affectivity, but not effortful control, are uniquely
      associated with obesogenic eating behaviors among low-income preschoolers.
AB  - Despite increased attention to the role of temperament in children's obesogenic
      eating behaviors, there is a paucity of research examining whether different
      dimensions of temperament may be differentially associated with specific eating
      behaviors among preschool-age children. The purpose of the current study was to
      examine whether three temperament dimensions (surgency, negative affectivity, and
      effortful control) were uniquely associated with six obesogenic eating behaviors
      (caregiver-reported food responsiveness, enjoyment of food, emotional overeating,
      satiety responsiveness, and tantrums over food; and observed eating in the
      absence of hunger) among low-income preschool-age children, covarying home
      environment quality. Results showed that temperament dimensions were
      differentially associated with different eating behaviors. Specifically,
      preschoolers with higher surgency were more likely to overeat in response to
      external cues, have frequent desire to eat, derive pleasure from food, and eat in
      the absence of hunger. In contrast, preschoolers with higher negative affectivity
      were more likely to have tantrums over being denied food and less likely to eat
      in the absence of hunger. Effortful control was not uniquely associated with
      obesogenic eating behavior. Findings remained significant even when home chaos
      was accounted for, suggesting that child surgency and negative affectivity are
      important to consider, independent of home environment. Results are discussed
      with regard to theoretical implications for the study of childhood obesity and
      for applied prevention implications. 

PMID- 24685764
TI  - Longitudinal predictors of frequent vegetable and fruit consumption among socio
      economically disadvantaged Australian adolescents.
AB  - Adequate vegetable and fruit consumption is necessary for preventing nutrition
      related diseases. Socio-economically disadvantaged adolescents tend to consume
      relatively few vegetables and fruits. However, despite nutritional challenges
      associated with socio-economic disadvantage, a minority of adolescents manage to
      eat vegetables and fruit in quantities that are more in line with dietary
      recommendations. This investigation aimed to identify predictors of more frequent
      intakes of fruits and vegetables among adolescents over a 2-year follow-up
      period. Data were drawn from 521 socio-economically disadvantaged (maternal
      education <=Year 10 of secondary school) Australian adolescents aged 12-15 years.
      Participants were recruited from 37 secondary schools and were asked to complete
      online surveys in 2004/2005 (baseline) and 2006/2007 (follow-up). Surveys
      comprised a 38-item FFQ and questions based on Social Ecological models examining
      intrapersonal, social and environmental influences on diet. At baseline and
      follow-up, respectively, 29% and 24% of adolescents frequently consumed
      vegetables (>=2 times/day); 33% and 36% frequently consumed fruit (>=1 time/day).
      In multivariable logistic regressions, baseline consumption strongly predicted
      consumption at follow-up. Frequently being served vegetables at dinner predicted
      frequent vegetable consumption. Female sex, rarely purchasing food or drink from
      school vending machines, and usually being expected to eat all foods served
      predicted frequent fruit consumption. Findings suggest nutrition promotion
      initiatives aimed at improving eating behaviours among this at-risk population
      and should focus on younger adolescents, particularly boys; improving adolescent
      eating behaviours at school; and encouraging families to increase home
      availability of healthy foods and to implement meal time rules.

PMID- 24685766
TI  - Detecting adverse drug reactions following long-term exposure in longitudinal
      observational data: The exposure-adjusted self-controlled case series.
AB  - Most approaches used in postmarketing drug safety monitoring, including
      spontaneous reporting and statistical risk identification using electronic health
      care records, are primarily suited to pick up only acute adverse drug effects.
      With the availability of increasingly larger electronic health record and
      administrative claims databases comes the opportunity to monitor for potential
      adverse effects that occur only after prolonged exposure to a drug, but analysis
      methods are lacking. We propose an adaptation of the self-controlled case series
      design that uses the notion of accumulated exposure to capture long-term effects
      of drugs and evaluate extensions to correct for age and recurrent events. Several
      variations of the approach are tested on simulated data and two large insurance
      claims databases. To evaluate performance a set of positive and negative control
      drug-event pairs was created by medical experts based on drug product labels and
      review of the literature. Performance on the real data was measured using the
      area under the receiver operator characteristics curve. The best performing
      method achieved an area under the receiver operator characteristics curve of 0.86
      in the largest database using a spline model, adjustment for age, and ignoring
      recurrent events, but it appears this performance can only be achieved with very
      large data sets.

PMID- 24685765
TI  - Silent atrial fibrillation after ischemic stroke or transient ischemic attack:
      interest of continuous ECG monitoring.
AB  - BACKGROUND: Since atrial fibrillation (AF) may be undiagnosed when asymptomatic
      and paroxysmal, we aimed to investigate the incidence and determinants of silent
      AF in patients with acute ischemic stroke or transient ischemic attack (TIA).
      METHODS: Consecutive patients admitted to the Stroke Unit of the University
      Hospital of Dijon, France, for acute ischemic stroke or TIA were prospectively
      enrolled from March to December 2012. Silent AF was assessed by continuous
      electrocardiography (ECG) monitoring for 24 h after admission. An
      echocardiography was performed at day 2 +/- 1 to measure left ventricular
      ejection fraction (LVEF) and left auricular (LA) dimensions. RESULTS: Among the
      187 patients included, 19 (10%) developed silent AF. Patients with silent AF were
      markedly older (76 vs. 66 years, p < 0.002), with lower creatinine levels (90 vs.
      80 umol/l, p = 0.030) and were less often smokers (5 vs. 24%, p = 0.058) than
      patients without silent AF. They also showed a trend towards more frequent
      hypertension and a recent history of infection. Patients with silent AF had a
      larger indexed LA volume (37.4 vs. 30.8 ml/m(3), p = 0.057) and LA diameter (23.2
      vs. 20.8 mm/m(2), p = 0.059). LVEF in the two groups was similar. In multivariate
      analysis, only age remained an independent estimate of silent AF. CONCLUSION:
      Silent AF detected by continuous ECG monitoring is common and closely associated
      with older age. Further studies are needed to investigate the interest of
      systematically screening for silent AF for secondary prevention after ischemic
      stroke/TIA.

PMID- 24685767
TI  - First TDCR measurements at low energies using a miniature x-ray tube.
AB  - Developed for radionuclide standardization using liquid scintillation, the Triple
      to Double Coincidence Ratio (TDCR) method is applied using coincidence counting
      obtained with a specific three-photomultiplier system. For activity
      determination, a statistical model of light emission is classically used to
      establish a relation between the detection efficiency and the experimental TDCR
      value. At LNE-LNHB, a stochastic approach of the TDCR modeling was developed
      using the Monte Carlo code Geant4. The interest of this TDCR-Geant4 model is the
      possibility to simulate the propagation of optical photons from their creation in
      the scintillation vial to the production of photoelectrons in photomultipliers.
      As an alternative to the use of radionuclide sources, first TDCR measurements are
      presented using a miniature x-ray tube closely coupled to the scintillation vial.
      The objective of this new set-up was to enable low-energy depositions (lower than
      20 keV) in liquid scintillator in order to study the influence of both time and
      geometrical dependence between PMTs already observed with radioactive sources. As
      for the statistical TDCR model, the non-linearity of light emission is
      implemented in the TDCR-Geant4 model using the Birks formula which depends on the
      kB factor and the scintillation yield. Measurements performed with the x-ray tube
      are extended to the assessment of these parameters and they are tested afterwards
      in the TDCR-Geant4 model for activity measurements of (3)H.

PMID- 24685768
TI  - Mechanisms of crosstalk between endocrine systems: regulation of sex steroid
      hormone synthesis and action by thyroid hormones.
AB  - Thyroid hormones (THs) are well-known regulators of development and metabolism in
      vertebrates. There is increasing evidence that THs are also involved in gonadal
      differentiation and reproductive function. Changes in TH status affect sex ratios
      in developing fish and frogs and reproduction (e.g., fertility), hormone levels,
      and gonad morphology in adults of species of different vertebrates. In this
      review, we have summarized and compared the evidence for cross-talk between the
      steroid hormone and thyroid axes and present a comparative model. We gave special
      attention to TH regulation of sex steroid synthesis and action in both the brain
      and gonad, since these are important for gonad development and brain sexual
      differentiation and have been studied in many species. We also reviewed research
      showing that there is a TH system, including receptors and enzymes, in the brains
      and gonads in developing and adult vertebrates. Our analysis shows that THs
      influences sex steroid hormone synthesis in vertebrates, ranging from fish to
      pigs. This concept of crosstalk and conserved hormone interaction has
      implications for our understanding of the role of THs in reproduction, and how
      these processes may be dysregulated by environmental endocrine disruptors. 

PMID- 24685769
TI  - Differential placental gene expression in term pregnancies affected by fetal
      growth restriction and macrosomia.
AB  - INTRODUCTION: Extremes of fetal growth are associated with increased perinatal
      mortality and morbidity and a higher prevalence of cardiovascular disease,
      obesity and diabetes in later life. We aimed to identify changes in placental
      gene expression in pregnancies with evidence of growth dysfunction and candidate
      genes that may be used to identify abnormal patterns of growth prior to delivery.
      METHODS: Growth-restricted (n = 4), macrosomic (n = 6) and normal term (n = 5)
      placentas were selected from a banked series (n = 200) collected immediately
      after caesarean section. RNA was extracted prior to microarray analysis using
      Affymetrix HG-U219 arrays to determine variation in gene expression. Genes of
      interest were confirmed using qRT-PCR. RESULTS: 338 genes in the growth
      restricted and 41 genes in the macrosomic group were identified to be
      significantly dysregulated (>2-fold change; p < 0.05). CPXM2 and CLDN1 were
      upregulated and TXNDC5 and LRP2 downregulated in fetal growth restriction. In
      macrosomia, PHLDB2 and CLDN1 were upregulated and LEP and GCH1 were
      downregulated. DISCUSSION: Dysfunctional growth is associated with differential
      placental gene expression and affects genes with a whole spectrum of
      developmental and cellular functions. Better elucidation of these pathways may
      allow the development of biomarkers to identify growth abnormalities and
      effective prenatal intervention.

PMID- 24685770
TI  - Stopped in its tracks: the RNA polymerase molecular motor as a robust sensor of
      DNA damage.
AB  - DNA repair is often a complex, multi-component, multi-step process; this makes
      detailed kinetic analysis of the different steps of repair a challenging task
      using standard biochemical methods. At the same time, single-molecule methods are
      well-suited for extracting kinetic information despite time-averaging due to
      diffusion of biochemical components and stochasticity of chemical reaction steps.
      Here we discuss recent experiments using DNA nanomanipulation in a magnetic trap
      to study the initiation of transcription-coupled repair in a model bacterial
      system comprising the canonical Escherichia coli RNA polymerase and the Mfd
      translocase which specifically binds to it. These experiments provide kinetic
      insight into the reaction process, helping to explain how Mfd discriminates
      between transcribing RNAP and stalled RNAP. They also identify a reliably long
      lived intermediate containing Mfd translocase and, potentially, RNA polymerase.
      This intermediate presumably serves as a platform for assembly of downstream
      repair components UvrAB(C). 

PMID- 24685771
TI  - Brain magnetic resonance imaging findings and auditory brainstem response in a
      child with spastic paraplegia 2 due to a PLP1 splice site mutation.
AB  - A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation
      of PLP1 presented with progressive spasticity of lower limbs, which was first
      observed during late infancy, when he gained the ability to walk with support.
      His speech was slow and he had dysarthria. The patient showed mildly delayed
      intellectual development. Subtotal dysmyelination in the central nervous system
      was revealed, which was especially prominent in structures known to be myelinated
      during earlier period, whereas structures that are myelinated later were better
      myelinated. These findings on the brain magnetic resonance imaging were unusual
      for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem
      response (ABR) were normally provoked, but peaks III-V were not clearly
      demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These
      findings of brain MRI and ABR may be characteristic for a subtype of SPG2
      patients. 

PMID- 24685775
TI  - Periodontal status in subjects with hyperlipidemia and determination of
      association between hyperlipidemia and periodontal health: a clinicobiochemical
      study.
AB  - AIM: The aim of this study was to assess the periodontal status in subjects with
      hyperlipidemia and to determine whether there is any association between
      hyperlipidemia and periodontitis. MATERIALS AND METHODS: Sixty subjects with
      hyperlipidemia and 60 normolipidemic subjects participated in the study.
      Biochemical parameters assessed included plasma triglyceride, total cholesterol,
      low density lipoprotein cholesterol (LDL-C) and high density lipoprotein
      cholesterol (HDL-C) levels. Periodontal parameters assessed included plaque index
      (PI), probing depth (PD), clinical attachment level (CAL) and percentage of sites
      with bleeding on probing (BOP). RESULTS: Hyperlipidemic patients showed
      signifcantly higher values across the four periodontal parameters. Plasma
      triglycerides, total cholesterol, LDL-C were signifcantly and positively
      associated with PD, BOP and CAL (p = 0.05). Whereas HDL-C levels were
      signifcantly and negatively associated with PD, BOP and CAL (p = 0.05).
      CONCLUSION: Patients with hyperlipidemia manifested higher values of periodontal
      parameters compared to control group. Poorly controlled hyperlipidemia had a
      destructive impact on periodontium. A cyclic relationship exists between serum
      lipids, periodontitis and systemic health. Clinical signifcance: The relationship
      between periodontium and systemic factors is bidirectional and interlinked.
      Therefore, dentists and physicians should take this into account while treating
      patients, aiming for the overall betterment of the patient.

PMID- 24685772
TI  - How useful are clinical liver function tests in in vitro human hepatotoxicity
      assays?
AB  - In preclinical hepatotoxicity testing cell based assays are frequently employed.
      However, prediction of clinical drug induced liver injury (DILI) remains a major
      challenge. Here we examined the usefulness of frequently employed markers of
      hepatocellular injury in cultures of primary human hepatocytes (PHH) in response
      to treatment with either paracetamol, rifampicin, petadolex and/or amiodarone.
      The changes in the metabolic competency (urea and albumin) and cellular injury
      (AST, ALT, ALP, LDH, gammaGT and succinate dehydrogenase) were determined at
      therapeutic and above drug concentrations as to evaluate the utility of these
      markers in in vitro systems. Initially, treatment of PHH with any of the drugs
      caused a statistically significant reduction in enzyme activities to suggest a
      switch from basic amino acid metabolism towards induced detoxification. However,
      treatment for prolonged periods of time caused cytolysis, as evidenced by the
      significant rise in extracellular LDH and the concomitant increase in ALT and AST
      activity. Notably, amongst the various endpoints studied, urea was best to
      demonstrate dose dependent metabolic stress, while other markers of
      hepatocellular injury were highly variable. Taken collectively, urea measurement
      proofed to be robust in predicting hepatocellular stress; therefore it should be
      included in preclinical testing strategies for an improved prediction of DILI. 

PMID- 24685773
TI  - Mutagenicity and clastogenicity of native airborne particulate matter samples
      collected under industrial, urban or rural influence.
AB  - Airborne particulate matter has recently been classified by the IARC as
      carcinogenic to humans (group 1). However, the link between PM chemical
      composition and its carcinogenicity is still unclear. The aim of the present
      study was to evaluate and to compare genotoxic potencies of 6 native PM samples
      collected in spring-summer or autumn-winter, either in industrial, urban or rural
      area. We evaluated their mutagenicity through Ames test on YG1041, TA98, and
      TA102 tester strains, and their clastogenicity on human bronchial epithelial BEAS
      2B cells using comet assay, gamma-H2AX quantification, and micronucleus assay.
      Ames test results showed a strong positive response, presumably associated with
      nitro-aromatics content. In addition, at least 2 positive responses were observed
      out of the 3 genotoxicity assays for each of the 6 samples, demonstrating their
      clastogenicity. Our data suggest that PM samples collected in autumn-winter
      season are more genotoxic than those collected in spring-summer, potentially
      because of higher concentrations of adsorbed organic compounds. Taken together,
      our results showed the mutagenicity and clastogenicity of native PM2.5 samples
      from different origins, and bring additional elements to explain the newly
      recognized carcinogenicity of outdoor air pollution.

PMID- 24685774
TI  - Detection of key enzymes, free radical reaction products and activated signaling
      molecules as biomarkers of cell damage induced by benzo[a]pyrene in human
      keratinocytes.
AB  - Benzo[a]pyrene (BaP) is a known carcinogenic and cell damaging agent. The
      underlying cell damaging pathomechanisms have not been totally revealed.
      Especially BaP-related induction of oxidative and nitrosative stress has not been
      previously investigated in detail. The presented study investigated these effects
      in order to elucidate the pathomechanism and as well to identify potential
      biological markers that may indicate a BaP exposure. Human immortalized
      keratinocytes (HaCaT cells) were exposed to BaP (1 MUM) for either 5 min or 6 h,
      respectively. BaP-induced cellular damage was evaluated by immunocytochemistry
      analysis of multiple signaling cascades (e.g. apoptosis, Akt, MAPK, NOS,
      nitrotyrosine and 8-isoprostane formation), detection of nitrosative stress using
      diaminofluorescein (DAF-FM) and oxidative stress using 3' -(p
      aminophenyl)fluorescein (APF). Our results show that BaP exposure significantly
      enhanced NO and ROS productions in HaCaT cells. BaP led to eNOS-phosphorylation
      at Ser(1177), Thr(495) and Ser(116) residues. Using specific inhibitors, we found
      that the Erk1/2 pathways seemed to have strong impact on eNOS phosphorylation. In
      addition, BaP-induced apoptosis was observed by caspase-3 activation and PARP
      cleavage. Our results suggest that BaP mediates its toxic effect in keratinocytes
      through oxidative and nitrosative stress which is accompanied by complex changes
      of eNOS phosphorylation and changes of Akt and MAPK pathways.

PMID- 24685776
TI  - Comparative evaluation of self-etching primers and phosphoric acid effectiveness
      on composite to enamel bond: an in vitro study.
AB  - AIM: The aim of the present study was to investigate the effectiveness of the one
      total-etch self-priming adhesive, one two-step self-etching primer adhesive, and
      one 'all-in-one' self-etching adhesive system on the adhesion of a resin
      composite to enamel. MATERIALS AND METHODS: Thirty-six freshly extracted human
      mandibular molars were selected for this study. A fat area about 5 mm in diameter
      was created on the exposed mesial surface of enamel of each tooth by moist
      grinding with 320, 420 and 600 grit silicon carbide paper. Twelve teeth were
      randomly assigned into three groups. In group 1, Adper Easy One (3M ESPE), a one
      step self-etching primer adhesive was applied and light curing unit for 10
      seconds. In group 2, Adper SE Plus, a two-step self-etching primer with bottle A
      containing the aqueous primer and bottle B containing the acidic adhesive was
      applied and light cured for 10 seconds. Group 3 (control)-etchant 37% phosphoric
      acid is applied to the surface for 15 seconds and rinsed with water and air dried
      and adhesive (single bond 2) is applied to the surface and tube is placed and
      light cured for 20 seconds. Composite material (Z350) was placed in the tube and
      light cured for 40 seconds in all the groups. Bond strength testing was done
      using universal testing machine at the enamel-composite interface. The debonded
      enamel surface was evaluated in stereomicroscope to assess the cohesive, adhesive
      or mixed fracture. Data was statistically analyzed by one way analysis of
      variance (ANOVA). RESULTS: Group 1 performed least among all groups with a mean
      score of 19.46 MPa. Group 2 had a mean score of 25.67 MPa. Group 3 had a mean
      score of 27.16 MPa. CONCLUSION: Under the conditions of this in vitro study, the
      bond strength values of the two-step self-etching primer systems tested were
      similar to the total-etch. And, one step self-etching primers have lower bond
      strength compared to the total-etch.

PMID- 24685777
TI  - Effect of the association between citric acid and EDTA on root surface etching.
AB  - OBJECTIVE: This study aims to compare the clot stabilization on root surfaces
      conditioned with citric acid and ethylenediamine-tetraacetic acid (EDTA).
      MATERIALS AND METHODS: Scaled root samples (n = 100) were set in fve groups:
      group I-control group (saline solution); group II (24% EDTA); group III (25%
      citric acid); group IV (EDTA + citric acid); group V (citric acid + EDTA). Fifty
      samples were assessed using the root surface modifcation index (RSMI). The other
      50 received a blood drop after conditioning. Clot formation was assessed using
      blood elements adhesion index (BEAI). A blind examiner evaluated
      photomicrographs. Statistical analysis considered p < 0.05. RESULTS: Groups-III
      and G-V attained the best results for RSMI and BEAI in comparison to control. The
      worst results for clot stabilization were seen in group-II. EDTA employment
      before citric acid (group-IV) reduced clot formation in comparison to citric acid
      use alone (group-III). CONCLUSION: Root conditioning with citric acid alone and
      before EDTA had the best results for smear layer removal and clot stabilization.
      EDTA inhibited clot stabilization on root surface and must have a residual
      activity once it has diminished clot adhesion to root even after citric acid
      conditioning. Thus, EDTA can be used to neutralize citric acid effects on
      periodontal cells without affecting clot stabilization. Clinical signifcance: To
      demonstrate that citric acid use on root surfaces previously affected by
      periodontal disease may favor clot stabilization and may have a benefcial effect
      on surgical outcomes. Also, EDTA can be used to neutralize citric acid effects on
      periodontal cells.

PMID- 24685778
TI  - Estimation of serum copper and zinc levels in oral submucous fibrosis: an atomic
      absorption spectroscopic study.
AB  - BACKGROUND AND OBJECTIVES: Biochemical derangements of microelements although
      reported in oral cancer is poorly understood in oral submucous fbrosis (OSMF).
      Hence, the present study was carried out to estimate and compare the serum copper
      and zinc levels among different histopathological stages of OSMF with that of
      healthy controls. MATERIALS AND METHODS: Thirty histopathologically diagnosed
      cases of OSMF and 30 healthy controls reporting to MS Ramaiah Dental College and
      Hospital (MSRDCH), Bengaluru, were included in the study. The histopathological
      staging of OSMF was done as per criteria given by Pindborg and Sirsat (1966).
      Blood samples were collected and the serum copper and zinc levels were estimated
      using atomic absorption spectroscopy. The results were statistically analyzed
      using independent t-test and Kruskal-Wallis test. RESULTS: The mean serum copper
      levels were increased (p < 0.0005) and zinc levels were decreased (p < 0.01) in
      OSMF patients when compared to that of controls. The mean serum copper levels
      showed an increasing trend from stage I to IV (p = 0.004) while zinc levels
      showed a decreasing trend from stage I to IV (p = 0.04) in OSMF patients.
      CONCLUSION: The serum copper and zinc levels in OSMF showed a signifcant
      difference in comparison to that of controls and between the histopathological
      stages. These fndings indicate that serum copper and zinc may have a contributory
      role in the etiopathogenesis of OSMF. CLINICAL RELEVANCE: Although the role of
      the trace elements as etiological factors is minor, derangements noted in the
      serum copper and zinc levels could be correlated with diseased progression and
      possibly explain the transformation of OSMF into malignancy. Thus, they can be
      used as prognostic markers and can be of value for proactive intervention.

PMID- 24685779
TI  - Objective evaluation of cervical vertebral bone age' its reliability in
      comparison with hand-wrist bone age: by TW3 method.
AB  - AIM: The aim of this study was to establish the validity of a new method for
      evaluating skeletal maturation by assessing the 3rd and 4th cervical vertebrae
      seen in the cephalometric radiograph. MATERIALS AND METHODS: This study consisted
      of a sample of 50 patients in the age group of 8 to 14 years of age.
      Chronologically, they were divided into six groups, based on the age consisting
      of a minimum of six to a maximum of 10 subjects. All the patients included in the
      study were females. The selected subjects were clinically examined and then age
      and date of birth of the patient in years and months was noted. Then lateral
      cephalograms and hand-wrist radiographs of the patient were taken on the same day
      with good clarity and contrast. RESULTS: The results suggested that cervical
      vertebral bone age on cephalometric radiographs calculated with this method is as
      reliable at estimating bone age as is the Tanner-Whitehouse 3 (TW3) method on
      hand-wrist radiographs. By determining the cervical vertebral bone age, skeletal
      maturity can be evaluated in a detailed and objective manner with cephalometric
      radiographs. CONCLUSION: The ability to accurately appraise skeletal maturity
      from cervical vertebral maturation, without the need for additional radiographs,
      has the potential to improve orthodontic diagnostic and therapeutic decisions.
      The technique's simplicity and ease of use should encourage this method as a frst
      level diagnostic tool to assess skeletal maturation. Clinical signifcance: This
      study revealed that the timing and sequence of ossifcation of the bones in hand
      and wrist and cervical vertebrae were able to relate the skeletal development of
      the various skeletal maturity indicators to a child's development. This method
      provided a mean with which one can determine the skeletal maturity of a person
      and thereby determine whether the possibility of potential growth existed.

PMID- 24685783
TI  - Effect of energy drinks on the surface texture of nanoflled composite resin.
AB  - OBJECTIVE: To study the effect of three energy drinks on the surface roughness of
      nanoflled composite resins after different periods of aging time. MATERIALS AND
      METHODS: Composite resin disks, 6 mm diameter, 3 mm thickness were prepared from
      Filtec Z350 XT, Tetric EvoCeram and Filtec Z250 XT. Specimens fr/8om each
      material were tested after aging with Red Bull, Bison and Power Horse energy
      drinks and distilled water as a control. Specimens were stored at 37 degrees C in
      dark containers for 1, 3 and 6 months. Surface roughness Ra was assessed using a
      surface scanning interferometry before and after each storage period. Surface
      roughness differences DeltaRa and Ra among specimens were measured. Mean values
      were statistically analyzed using multiple repeated measured (ANOVA), variance
      and multiple comparisons of the mean values were done with Bonferroni test, with
      p < 0.05 as signifcance level. RESULTS: The surface roughness degradation change
      DeltaRa and Ra value before and after occurred by Red Bull, Bison and Power Horse
      energy drinks was signifcantly different for all tested materials at all three
      times p < 0.05. All specimens showed increase in surface roughness changes after
      aging periods of 1, 3 and 6 months. The highest total surface roughness
      difference DeltaRa and Ra was found in the Red Bull group after 6 months.
      CONCLUSION: Energy drinks used in this study had surface degradation effect on
      the tested composite resin materials. The surface roughness increased with aging
      time however, it was clinically acceptable in all test groups after 6 months. The
      effect of energy drinks solutions on the surface roughness parameter of resin
      composites depends on type of solution and its acidity contents.

PMID- 24685782
TI  - An in vitro study to compare the effectiveness of F-fle with ultrasonically
      activated K-fle to remove smear layer by using a scanning electron microscope.
AB  - AIM: The aim of this study was to compare the effectiveness of the F-fle with an
      ultrasonically activated #15 K-fle in removing the smear layer after
      biomechanical instrumentation along with irrigation of Saline, NaOCl and with or
      without a fush of EDTA. MATERIALS AND METHODS: Sixty decoronated human premolar
      teeth with a single canal were instrumented with ProTaper using S1, S2 and F1
      series to produce the smear layer and randomly divided into two groups. Group A
      used Ultrasonics and group B used F-fle for activation of irrigants respectively.
      Each group was further divided in to three subgroups consisting of 10 teeth in
      each as I, II, III consisting of saline, NaOCl, NaOCl and EDTA as irrigants
      respectively. SEM micrographs were taken and amount of smear layer removal was
      analyzed by using Chi-square statistics tests. RESULTS: Most effective smear
      layer removal was seen only when EDTA was used. There was no statistically
      signifcant difference between the groups A and B in removal of smear layer.
      CONCLUSION: There was no increase in smear layer between use of F-fle when
      compared with the Ultrasonically activated K-fle. CLINICAL SIGNIFCANCE: The F-fle
      although does not have a superior effcacy than the ultrasonics in removal of
      smear layer from root canals but when used along with EDTA, can be an effective
      alternative for the dentists who are unable to bear the initial setup cost of
      ultrasonics.

PMID- 24685780
TI  - Comparison of the serum immunoglobulin IgM level in diabetic and nondiabetic
      patients with chronic periodontitis.
AB  - AIM: To evaluate and compare the serum IgM level in diabetic and nondiabetic
      patients with chronic periodontitis. MATERIALS AND METHODS: A total of 60
      patients were selected for the study and divided into four groups, diabetic with
      periodontitis, diabetic without periodontitis, nondiabetic with periodontitis and
      nondiabetic without periodontitis (control) were analyzed for the quantitative
      estimation of serum immunoglobulins M by turbidimetric immunoassay. The serum of
      the diabetic and nondiabetic patients was evaluated and turbidimetric method was
      used for immunological assay by using Quantia IgM turbidimetric immunoassay for
      estimation of immunoglobulin IgM in human serum. The data for the level of
      immunoglobulin thus obtained were compared with clinically healthy patient taken
      as control. Sugar level was estimated the by checking the random blood sugar
      level by glucose test kit based on end point and kinetic assay and compared with
      the HbA1c percentage of the patients, by using NycoCard Reader. RESULT: The group
      A patients having diabetes with periodontitis showed nonsignifcant increase in
      serum IgM level as compared to controls and other groups. Group B showed
      signifcance of p = 0.074. Group C showed signifcance of p = 0.982 and group D
      showed signifcance of p = 0.520. There was signifcant increase in HbA1c with an
      increase percentage serum IgM. CONCLUSION: In the present study, significantly
      high concentrations of the IgM in serum of diabetic and nondiabetic patients were
      found as compared to the healthy subjects who had neither diabetes nor
      periodontitis. CLINICAL SIGNIFCANCE: By this study, we can emphasize on the fact
      of the importance of the immune system and its correlation with glycemic control,
      especially in patients diagnosed with periodontitis, also suggests that the
      alteration in immune response in poorly controlled diabetic patients may
      contribute to the pathogenesis of periodontitis and is the cause of increased
      incidence of periodontitis in patients with diabetes.

PMID- 24685781
TI  - The effects of phase III cardiac rehabilitation in serum and salivary Hs-CRP and
      anthropometric measurements in patients with coronary artery disease.
AB  - AIM: Cardiac rehabilitation is a key part in the treatment of coronary artery
      disease (CAD) by its anti-infammatory effects. However, the effect of exercise
      training programs on salivary concentrations of high-sensitivity C-reactive
      protein (hs-CRP) in patients with coronary artery disease has not been well
      studied. The objective of this study was to evaluate the effect of phase III
      cardiac rehabilitation on serum and salivary levels of hs-CRP, in relation to the
      anthropometric measurements of obesity and the relationship between salivary and
      serum levels of hs-CRP in CAD male patients. MATERIALS AND METHODS: Forty male
      volunteers (45-75 years) with CAD participated in 6 to 8 weeks of moderate
      intensity aerobic exercise training consisting of 45 minutes sessions of
      treadmill, stationary bicycle and arm ergometer. Anthropometric measurements of
      obesity, serum level of hs-CRP, stimulated and nonstimulated salivary level of hs
      CRP were measured at the beginning, in the middle and at the end of exercise
      sessions. RESULTS: All anthropometric measurements increased (p < 0.05) following
      cardiac rehabilitation except waist-hip ratio. Serum hs-CRP level reduced by 36%
      independent to the anthropometric measurements changes. Stimulated and
      nonstimulated salivary hs-CRP level decreased 68 and 54%, respectively, after 24
      sessions of cardiac rehabilitation. Nonstimulated salivary hs-CRP levels
      correlated to serum levels of hs-CRP at baseline and after 24 sessions (p <
      0.05). CONCLUSION: Phase III cardiac rehabilitation seems to be effective to
      improve serum and salivary hs-CRP concentrations independent of anthropometric
      measurements. CLINICAL SIGNIFICANCE: Nonstimulated salivary hs-CRP measurement
      could be a surrogate for blood measurement of hs-CRP during cardiac
      rehabilitation in male patients with CAD.

PMID- 24685784
TI  - A cephalometric study to determine the center of anteroposterior curve of
      occlusion in the cranium.
AB  - Proper management of the occlusal plane is an essential consideration when
      multiple long span posterior restorations are designed. When restorations are
      added to an existing tooth arrangement characterized by rotated, tipped or
      extruded teeth, excursive interferences may be incorporated. The curve of Spee
      which exists in natural dentition, allows harmony to exist between the anterior
      teeth and the condylar guidance. Broadrick fag or occlusal plane analyzer is used
      to assist in the reproduction of tooth morphology that is commensurate with the
      curve of Spee when posterior restorations are designed; its use prevents the
      introduction of protrusive interferences. The current study determines the
      relationship of the center of anteroposterior curve of occlusion in the cranium
      and its relationship to other cephalometric landmarks and also evaluates the
      relationship of anteroposterior curve of occlusion to the condyle.

PMID- 24685785
TI  - An in vitro comparison of antimicrobial effcacy of three root canal irrigants
      BioPure MTAD, 2% chlorhexidine gluconate and 5.25% sodium hypochlorite as a final
      rinse against E. faecalis.
AB  - AIM: This study was conducted to evaluate the antimicrobial activity of 5.25%
      sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) and BioPure MTAD when used as
      a fnal rinse against Enterococcus faecalis. MATERIALS AND METHODS: Sixty single
      rooted premolars were biomechanically prepared, inoculated with E. faecalis and
      divided into various groups. These were then irrigated with the test irrigants
      and tested microbiologically for growth of E. faecalis immediately after
      irrigation and after 48 hours. RESULTS: Statistical analysis showed that there
      was a signifcant difference between the antibacterial activities of BioPure MTAD,
      2% CHX and 5.25% NaOCl at 5 minutes; however, the antibacterial activities of the
      three irrigants were comparable after 2 days of irrigation. CONCLUSION: The
      present study concludes that BioPure MTAD is as effective against E. faecalis as
      5.25% NaOCl and more effective than 2% CHX. CLINICAL SIGNIFCANCE: E. faecalis is
      one of the most resistant intracanal species and a possible cause of root canal
      failure. Many authors have stressed the importance of using antimicrobial
      irrigants during chemomechanical preparation to ensure complete disinfection.
      Therefore, various irrigating solutions have been used during and immediately
      after root canal preparation to remove debris and necrotic pulp tissue and to
      eliminate microorganisms that cannot be reached by mechanical instrumentation.

PMID- 24685787
TI  - An investigation of blood hemogram and estimation of serum iron and protein
      levels in aggressive periodontitis patients: a clinic biochemical study.
AB  - AIM: The aim of this study is to investigate the blood hemogram and estimation of
      serum iron and proteins level in aggressive periodontitis patients. MATERIALS AND
      METHODS: A total of 85 patients were selected and divided into two groups, 45
      patients are with aggressive periodontitis and 40 patients are healthy.
      Periodontal parameters such as gingival infammation oral hygiene index, Russell's
      periodontal index and radiograph were taken. Total 10 ml blood was collected and
      sent for estimation of blood hemogram protein estimation and serum
      electrophoresis. RESULTS: There was statistical signifcant difference observed in
      relation to gingival infammation oral hygiene hemoglobin and total iron binding
      capacity level between both the groups. CONCLUSION: It has been concluded that
      periodontitis does not induce anemia like state, as the hematological and
      biochemical parameters were almost equally affected in periodontally healthy and
      periodontally diseased individuals, but some parameters showed statistical
      significant difference between the both groups. CLINICAL SIGNIFICANCE: In the
      present study, the clinical periodontal parameters, red blood cell parameters and
      serum iron and ferritin levels were compared among control and test groups. It
      was found that the values of gingival infammation, oral hygiene and periodontal
      index, hemoglobulin level and total iron binding protein were statistically
      signifcant between the groups. However, the values of erythrocyte count, white
      blood cell count, serum iron and serum proteins, serum electrophoresis did not
      show any signifcant correlation.

PMID- 24685786
TI  - Compare the effcacy of two commercially available mouthrinses in reducing viable
      bacterial count in dental aerosol produced during ultrasonic scaling when used as
      a preprocedural rinse.
AB  - AIM: To evaluate and compare the effcacy of preprocedural mouthrinses
      (chlorhexidine digluconate and tea tree oil) in reducing microbial content of
      aerosol product during ultrasonic scaling procedures by viable bacterial count.
      SETTINGS AND DESIGN: It was a randomized single blind, placebo-controlled
      parallel group study. MATERIALS AND METHODS: Sixty subjects were randomly
      assigned to rinse 10 ml of any one of the mouthrinses (chlorhexidine digluconate
      or tea tree oil or distilled water). Ultrasonic scaling was done for a period of
      10 minutes in presence of trypticase soy agar plates placed at standardized
      distance. Plates were then sent for microbiological evaluation for the aerosol
      produced. RESULTS: This study showed that all the antiseptic mouthwashes
      signifcantly reduced the bacterial colony forming units (CFUs) in aerosol
      samples. Chlorhexidine rinses were found to be superior to tea tree when used
      preprocedurally in reducing aerolized bacteria. CONCLUSION: This study advocates
      preprocedural dural rinsing with an effective antimicrobial mouthrinse during any
      dental treatment which generates aerosols, reduces the risk of cross
      contamination with infectious agents in the dental operatory. CLINICAL
      SIGNIFICANCE: The aerolization of oral microbes occurring during dental
      procedures can potentially result in cross-contamination in the dental operatory
      and transmission of infectious agents to both dental professionals and patient.
      It is reasonable to assume therefore, that any stratagem for reducing the viable
      bacterial content of these aerosols could lower the risk of cross-contamination.

PMID- 24685789
TI  - The effect of different bracket base cleaning method on shear bond strength of
      rebonded brackets.
AB  - AIM: To assess the effect of different bracket base conditioning method on shear
      bond strength (SBS) of rebonded brackets. MATERIALS AND METHODS: Eighty brackets
      were bonded to freshly extracted premolar teeth using light cured composite
      adhesive. SBS was measured for 20 random samples as control group (G1). After
      debonding, 60 debonded brackets were allocated randomly into three groups of
      bracket base conditioning methods to remove the remaining adhesives. G2: bracket
      base cleaned with slow speed round carbide bur (CB), G3: cleaned with ultrasonic
      scaler (US), G4: cleaned with sandblasting (SB). After that, brackets were
      rebonded in the same manner as frst bonding and SBS was measured. Modifed
      adhesive remnant index (ARI) was recorded for all groups. RESULTS: SBS for new
      brackets was 11.95 MPa followed by 11.65 MPa for G2, 11.56 MPa for G4 and 11.04
      MPa for G3 group. There were no statistically signifcant differences between all
      groups (p = 0.946). In all groups, failure mode showed that the majority of
      adhesive composite remained on the bracket base with ARI of 4. There was no
      statistically signifcant difference between all groups in ARI (p = 0.584).
      CONCLUSION: In-offce methods; slow speed CB and US are effective, quick and cheap
      methods for bracket base cleaning for rebonding.

PMID- 24685788
TI  - Effectiveness of desensitizing agents in relieving the pre- and postcementation
      sensitivity for full coverage restorations: a clinical evaluation.
AB  - Patients frequently report sensitivity of prepared abutment teeth during the
      temporization period and after the fnal cementation of full coverage restoration.
      Purpose of this clinical investigation was to evaluate the effectiveness of
      desensitizing agents in reducing the pre- and postcementation sensitivity for
      full coverage restorations and to compare the relative effcacy of three in offce
      applied desensitizing agents in relieving the postcementation sensitivity with
      the use of glass ionomer luting cement. MATERIALS AND METHODS: This study
      consisted of 30 patients requiring either full coverage restoration or 3 unit
      fxed partial denture. Total of 40 restorations (n = 40) were made and were
      randomly assigned into four groups comprising 10 restoration (n = 10) in each
      group. Group C control where no desensitizer application was done, group BB
      applied with BisBlock dentin desensitizer (Bisco Inc.), group ST applied with
      Systemp desensitizer (Ivoclar Vivadent), group GC applied with GC Tooth Mousse
      desensitizer (GC Asia). Desensitizer application was done immediately after the
      tooth preparation. Sensitivity of the tested abutment was determined by the
      patient response to cold, hot and bite stimuli and were recorded on visual analog
      scale (VAS). Sensitivity level scores was evaluated at 4 time intervals, i.e. 1
      week after desensitizer application at baseline precementation appointment and
      others at 5 minutes, 1 day and 1 week postcementation appointment. VAS score data
      was statistically analyzed using one-way ANOVA followed by post hoc Tukey's test.
      RESULTS: BisBlock and GC Tooth Mousse desensitizer resulted in statistically
      signifcant (p < 0.01) reduction in postcementation sensitivity of glass ionomer
      cement in comparison to Systemp desensitizer at 5 minutes, 1 week postcementation
      time interval with no statistical difference was seen between all desensitizer
      groups at 1 day postcementation. Application of BisBlock and GC Tooth Mousse
      desensitizer resulted in highly signifcant (p < 0.01) reduction in sensitivity
      level at the end of 1 week. CLINICAL SIGNIFICANCE: Desensitizer's application on
      the prepared abutment teeth is considerably effective in relieving both pre- and
      postcementation sensitivity for full coverage restoration over the short duration
      of time. Immediate reduction in postoperative sensitivity relatively in a short
      time period may be benefcial in terms of patient's comfort. Nonetheless,
      multicenter long-term clinical trials should be conducted to confrm the results.
      CONCLUSION: Efficacy of BisBlock and GC Tooth Mousse desensitizer was more in
      relieving the postcementation sensitivity of glass ionomer cement at various time
      intervals in comparison to Systemp desensitizer. In conclusion, application of
      desensitizers was beneficial to reduce the pre- and postcementation abutment
      sensitivity.

PMID- 24685790
TI  - Antioxidant agents and their effects on shear bond strength of bleached enamel.
AB  - AIM: The goal of this study was to fnd a method to eliminate bond strength
      reduction after vital bleaching. MATERIALS AND METHODS: Sixty fat surfaces of
      enamel central human incisors were prepared by diamond disks. In the frst group,
      the samples immediately bonded to the tooth after bleaching. For the second
      group, the bleached samples were treated by sodium ascorbate for 1 hours. In the
      third and fourth groups the treatment was down using a new antioxidant agent for
      1 hour and 15 minutes respectively. For the ffth group no bleaching was done.
      Cylindrical composite resin (Z 100) with a Single Bond adhesive system was bonded
      to the enamel with a special metal mold. After thermocycling, the samples were
      loaded at a crosshead speed of 0.5 mm/min. The mode of failures was inspected by
      the Dino Lite microscope and the microstructure of the debonding surfaces was
      observed by SEM. Considering normal data, statistical analysis was conducted by
      ANOVA and Tukey tests (p = 0.05). RESULTS: The fourth group had maximum (21.82),
      while the frst group had the least (9.0971) shear bond strength. The ANOVA test
      showed a signifcant difference among the fve groups (p = 0.0002). There was not
      any signifcant statistical difference between the three types of debonding (p =
      0.165). CONCLUSION: The usage of sodium ascorbate or sodium ascorbate with
      detergent after vital bleaching are effective methods for reducing the damaging
      effects of bleaching agents on the shear bond strength of composite resin
      restoration to enamel. CLINICAL SIGNIFCANCE: Using antioxidants is necessary post
      bleaching and before resin bonding.

PMID- 24685791
TI  - Long-term surface hardness and monomer conversion of a nanoflled and a
      microhybrid composite resin.
AB  - OBJECTIVE: This study aims to evaluate the degree of conversion (DC) and
      hydrolytic degradation through the Vickers hardness test (HV) of a nanoflled
      (Filtek(TM) Z-250, 3M) and a microhybrid (Filtek(TM)Supreme-XT, 3M) composite
      resin. MATERIALS AND METHODS: Eight disk-shaped specimens (4 mm diameter * 2 mm
      thick, ISO 4049) of each material were prepared for each test. Composites were
      inserted into single increment in a metallic matrix and light-cured for 40
      seconds. VH readings were performed for each specimen at predetermined intervals:
      immediately after polymerization (control), 1, 2, 3, 7, 14, 21, 30 and 180 days.
      After curing, initial hardness measurements were performed and the specimens were
      immersed in artifcial saliva at 37 degrees C. For DC (%), specimens were ground,
      pressed with KBr and analyzed by FT-IR spectrophotometer. RESULTS: Student t-test
      showed that there was no difference between the resins for DC (p = 0.252). ANOVA
      analysis revealed that Z-250 VH means were all greater than S-XT, for both top
      and bottom surfaces, whatever the storage-period in artifcial saliva (p < 0.001).
      After 180 days of storage, the hardness obtained for S-XT was similar with that
      at the baseline, for both top and bottom surfaces. While for Z-250 hardness was
      not signifcantly different from baseline only for top surface, but there was a
      signifcant decrease observed in hardness for bottom surface. CONCLUSION: The
      materials tested showed no evidence of hydrolytic degradation in a signifcant
      way, in a 6-month storage-time in artifcial saliva. Nanoflled resin presents a
      monomer conversion comparable to the conventional microhybrid.

PMID- 24685792
TI  - Flowable composite an alternative orthodontic bonding adhesive: an in vitro
      study.
AB  - OBJECTIVE: To determine the clinical applicability of Ormocer based fowable
      adhesive (Admira fow) in comparison with BisGMA based adhesive (Transbond XT) and
      Ormocer based packable adhesive (Admira). MATERIALS AND METHODS: Sixty human
      premolars, divided into group I (n = 20) Transbond XT, group II (n = 20) Admira
      and group III (n = 20) Admira fow were bonded with metal brackets using
      adhesives. Brackets were debonded in shear on an Instron universal testing
      machine with a crosshead speed of 1 mm per minute. The mode of bond failure was
      determined by modifed ARI index. RESULTS: The results obtained from SBS
      evaluation and modifed ARI showed highest shear bond strength for Transbond XT
      (SD 11.64) 3.68 followed by Admira fow (SD 11.0) 2.87 and least for Admira (SD
      9.42) 2.21. However, the difference was not statistically signifcant, but an
      intergroup comparison done using Independent student 't' test, showed statically
      signifcant difference between Transbond XT and Admira. Kaplan-Meier survival
      analysis showed least survival median value for Admira, but the survival median
      value is not statistically signifcant among the three groups. All groups had
      modifed ARI score of three (60-70%), suggestive of cohesive type of failure.
      CONCLUSION: The in vitro study showed that fowable Ormocer can be an good
      alternative to commonly used BisGMA based adhesive but the its effcacy needs
      clinical assessment through a survival analysis. CLINICAL SIGNIFCANCE: Admire fow
      can defnitely be considered as an alternative bonding system due to their
      comparable bond strength and debonding characters and reported properties of
      biocompatibility.

PMID- 24685794
TI  - Shear bond strength of acrylic teeth to acrylic denture base after different
      surface conditioning methods.
AB  - BACKGROUND AND OBJECTIVES: Acrylic resin ruled the dental profession for 60
      years, and this success is attributed to its aesthetics, handling properties,
      physical and biological compatibility, its stability in oral environment and its
      cost effectiveness. The objective of this study is to evaluate and compare the
      bond strength of acrylic resin teeth treated with various conditioning materials
      like monomer and silane coupling agent. METHDOLOGY: A study was carried out in
      which 96 samples were grouped into 3 groups with a sample size of 32 each (16
      premolars, 16 molars). They were conditioned with different conditioning
      materials i,e monomer and silane coupling agent. Monomer, Silane coupling agent
      are coated on the ridge lap area before thermocycling and cured according to the
      manufacturer recommendations. The samples are retained from the fask; trimmed and
      polished. The samples are then subjected to shear bond strength using the
      Insteron Universal Testing Machine. RESULTS: In the present study it was found
      that application of monomer increased the bond strength between acrylic teeth and
      denture base, when compared to the conventionally processed samples. However it
      was found that application of silane coupling agent further increased the shear
      bond strength between acrylic teeth and denture base. Interprations and
      CONCLUSIONS: Within the confnes of this study it is found that there was a
      signifcant improvement in the bond strength between the acrylic teeth and denture
      base when silane coupling agent and monomer were used as surface conditioning
      material. The order of shear strength of samples is control > monomer > silane
      coupling agent.

PMID- 24685793
TI  - Fluoride releasing and uptake capacities of esthetic restorations.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate and compare
      in vitro the fuoride release and uptake from 5 different esthetic restorative
      materials. MATERIALS AND METHODS: Materials tested were conventional GIC - Fuji
      7, GC (group1), resin modifed GIC - Vitremer, 3M ESPE (group 2), polyacid modifed
      composite - Dyract, Dentsply (group 3), fuoride releasing composite - Tetric
      ceram, Ivoclar Vivadent (group 4), Giomer-Beautifl, Shofu (group 5). Fluoride
      release was estimated at 6th, 24th, 48th hour and weekly interval for 5 weeks.
      For fuoride recharge, each specimen was exposed to 2 ml of 1.23% APF gel for 4
      minutes and fuoride release measured at 1st, 2nd, 3rd day and 7th day. The
      fuoride release and recharge was measured using fuoride ion specifc electrode.
      RESULTS: ANOVA and Tukey HSD test were used for statistical analysis. During
      tested period all materials showed statistically different capability to release
      and uptake fuoride. Groups 1 and 2 results were comparable in fuoride release.
      Similarly groups 3 and 5. Groups 1 and 2 vs 3, 4, 5 were statistically very
      highly signifcant. Only conventional GIC showed initial 'burst effect'.
      INTERPRETATION AND CONCLUSION: Materials tested showed potential for fuoride
      release and recharge. Different esthetic materials had variable fuoride release
      hence selection of materials should be guided by specifc clinical situations.

PMID- 24685795
TI  - Comparative evaluation of shear compressive bond strength between cross-linked
      acrylic resin denture base and cross-linked acrylic resin teeth with different
      modifcations of their ridge lap surfaces.
AB  - A major problem commonly observed in denture wearer is the detachment of
      artifcial tooth/teeth from acrylic denture base. The problem was grave when
      porcelain teeth used along with the then available denture base materials. The
      bond formed was purely mechanical and hence debonding of teeth from denture base
      was a frequent occurrence. Inspite of chemical union between acrylic resin teeth
      and acrylic denture base material, detachment of teeth particularly anterior
      teeth is a frequent observation. The objective of the study is to study the
      effect of change in the surface treatment and surface confguration of ridge lap
      surface of the teeth on retention of cross-linked acrylic teeth on cross-linked
      acrylic resin denture base. Sixty specimens were tested for the shear compressive
      bond strength using instron universal testing machine in KN. Statistical analysis
      is used. The fndings were analyzed using one-way analysis of variance (ANOVA) and
      't' test. Slight modifcation in the ridge lap surface of artifcial teeth alters
      the strength of the shear compressive bond. Sand papering of ridge lap surfaces
      improves the shear compressive bond then the one without any modifcation. Maximum
      shear compressive bond strength can be increased by application of monomer.

PMID- 24685796
TI  - A study to evaluate the frequency and association of various mucosal conditions
      among geriatric patients.
AB  - Geriatric dentistry or gerodontics is the delivery of dental care to older adults
      involving the diagnosis, prevention and treatment of problems associated with
      normal aging and age-related diseases as part of an interdisciplinary team with
      other health care professionals. AIM: To evaluate the oral mucosal status in the
      elderly population of different age group and fnd out the association of age,
      gender and denture with oral mucosal disorders. MATERIALS AND METHODS: The study
      sample consisted of 570 geriatric persons concentrating mainly on the oral
      mucosal changes or lesions occurring in the geriatric population. Individuals
      those are aged above 60 years were selected, and all the examined geriatric
      persons were categorized into 3 age groups to fnd out the association of oral
      mucosal lesions in each group. Group I-60 to 65 years, Group II-66 to 70 years,
      Group III-71 and above years. RESULTS: The sample of 570 elderly patients
      included 279 (48.95%) men and 291 (51.05%) women in three age groups: 61 to 65
      years (40.35%), 66 to 70 years (31.05%), and 71 years and older (28.60%). The
      sample included 254 (44.56%) dentate patients, 205 (35.96%) denture wearers
      (partial and complete denture wearers) and 111 (19.47%) edentulous persons who
      lacked dentures in both the jaws. Almost half of the patients examined (48%) had
      one or more oral mucosal lesions. The 48% of the patients who presented with oral
      mucosal lesions, twenty fve different oral mucosal conditions were identifed and
      the three most common fndings were lingual varices (13.68%), denture induced
      infammatory fbrous hyperplasia (4.21%), squamous cell carcinoma (4.21%). There
      was some differences in the distribution of oral mucosal condition among the
      sexes. Leukoplakia and dysplasia were signifcantly associated with men (p <
      0.001) whereas the association of fbroma and lichen planus with women were
      signifcant (p < 0.001). CONCLUSION: In our study it was found that patients in
      groups II and III had more prevalence of oral mucosal disorders. Lingual varices,
      oral squamous cell carcinoma, fbroma and denture induced infammatory fbrous
      hyperplasia were more commonly associated with the geriatric patients. The oral
      lesions (fbroma and lichen planus) were strongly associated with women while
      leukoplakia was strongly associated with men. Ageing is an important factor that
      can infuence the occurrence of mucosal lesions and with age the oral mucosa
      becomes more permeable to noxious substances and more vulnerable to external
      carcinogens.

PMID- 24685797
TI  - Comparison of mutans streptococcal strains of father, mother, and child in indian
      families using chromosomal DNA fingerprinting.
AB  - INTRODUCTION: It is now understood and accepted that there is a direct
      transmission of mutans streptococci (MS) from the mother to the child. There is
      also a direct correlation between the levels of MS in the mother and the caries
      status of the child. Advanced technologies in molecular biology like chromosomal
      DNA fngerprinting have established beyond doubt that the mother and the child
      bear similar strains of MS. AIM: A study was designed with the aim of comparing
      the MS strains between the father, mother and the child in Indian families.
      MATERIALS AND METHODS: A group of 20 Indian families comprising of the father,
      mother and child were selected and divided into caries free and caries active
      groups. Mixed salivary samples were collected from the individuals and were
      cultured for the growth of Mutans streptococci. The colonies were counted on a
      colony counter and a comparison was made between the mutans streptococcal counts
      of the mother and the caries status of the child. Further, the genotypes of the
      father, mother and the child were isolated and compared using the technique of
      chromosomal DNA fngerprinting. Following electrophoresis, the band pattern
      obtained was compared for similarities or differences. The results of the same
      were tabulated and evaluated statistically. RESULTS: When the colony counts of
      the mother (in CFU/ml) were compared with the 'dft' status of the child, a
      positive correlation was seen in group II. Intergroup comparison using the
      unpaired T test was statistically signifcant. Electrophoretic analysis of the
      chromosomal DNA on the agarose gels revealed identical band patterns in 13 mother
      child pairs, which was statistically signifcant. Three of the father-child pairs
      showed identical band patterns, which was statistically signifcant. Intergroup
      comparison using Chi-square test was not statistically signifcant. CONCLUSION:
      One may conclude that irrespective of the caries status of the child, majority of
      the mother child pairs share identical strains of MS and hence the mother is the
      primary source of infection. However, in children with a high dft, the father may
      also play an important role in the acquisition and transmission of MS.

PMID- 24685799
TI  - Evaluating the antimicrobial activity of commercially available herbal
      toothpastes on microorganisms associated with diabetes mellitus.
AB  - AIM: The present study was conducted to evaluate the effcacy of commercially
      available herbal toothpastes against the different periodontopathogens. MATERIALS
      AND METHODS: Six herbal toothpastes that were commonly commercially available
      were included in the study. Colgate herbal, Babool, Meswak, Neem active, Dabur
      red toothpastes were tested for the study whereas sterile normal saline was used
      as control. Antimicrobial effcacies of dentifrices were evaluated against
      Streptococcus mutans and Actinobacillus actinomycetemcomitans. The antimicrobial
      properties of dentifrices were tested by measuring the maximum zone of inhibition
      at 24 hours on the Mueller Hinton Agar media inoculated with microbial strain
      using disk diffusion method. Each dentifrice was tested at 100% concentration
      (full strength). RESULTS: The study showed that all dentifrices selected for the
      study were effective against the entire test organism but to varying degree. Neem
      active tooth paste gave a reading of 25.4 mm as the zone of inhibition which was
      highest amongst all of the test dentifrices. Colgate Herbal and Meswak
      dentifrices recorded a larger maximum zone of inhibition, measuring 23 and 22.6
      mm respectively, compared to other toothpastes. All other dentifrices showed the
      zone of inhibition to be between 17 and 19 mm respectively. CONCLUSION: The
      antibacterial properties of six dentifrices were studied in vitro and concluded
      that almost all of the dentifrices available commercially had antibacterial
      properties to some extent to beneft dental health or antiplaque action.

PMID- 24685798
TI  - A comparative evaluation of shear bond strength of different pits and fissure
      sealants: an in vitro study.
AB  - AIM: The aim of this study was to determine and compare the shear bond strength
      of three different pits and fssure sealants to enamel namely, Delton, Clinpro and
      Z350 Filtek fowable composite. MATERIALS AND METHODS: Ninety permanent molars
      were divided into three groups of 30 each. Their proximal surfaces were prepared
      and stored in 37 degrees C +/- 5 degrees C normal saline for 24 hours. Sealant
      buttons were prepared. The specimens were tested in a shear mode (Lloyds LR100K)
      at a crosshead speed of 0.5 mm/min. The mean and standard deviations were
      subjected to an analysis of variance. RESULTS: The mean shear bond strength of
      samples of Delton was 10.33 MPa; Clinpro was 8.51 MPa and Z350 Filtek fowable was
      12.17 MPa. The mean strength of Delton was signifcantly higher as compared to
      Clinpro whereas the mean strength of Z350 Filtek was signifcantly higher as
      compared to Delton and Clinpro (Student t-test, p < 0.001). CONCLUSION: Z350
      Filtek fowable composite had maximum shear bond strength than Delton FS sealant
      followed by Clinpro sealant. Clinical signifcance: In this study, we compare the
      bond strength of three pits and fssure sealant, Clinpro yielded lower bond
      strength than Delton. This outcome can be described due to the presence of fllers
      in Delton, since these particles increase the resistance of the material to
      abrasion and also increase the mechanical resistance of the material.

PMID- 24685800
TI  - A comparative clinical evaluation of diet intake and effect of various nutritions
      on aggressive periodontitis patients.
AB  - AIM: The aim of this study is to investigate the effect various dietary nutrients
      in aggressive periodontitis patients. MATERIALS AND METHODS: A total of 85
      patients were selected and divided into two groups, 45 patients are with
      aggressive periodontitis and 40 patients are healthy. Periodontal parameters such
      as oral hygiene index, Russels periodontal index and radiograph were taken. The
      food consumption survey was conducted in all the households of subjects both in
      control and experimental group. The individual of food intake of the subjects was
      assessed by the oral questionnaire (24 hours recall) method. The quantity of raw
      foods used for various preparations and volumes of cooked quantities of such
      preparations in terms of standardized cups were noted. Body measurements were
      taken on all the subjects, standing height using a height measuring rod and
      weight in standard weighing machine. RESULTS: Aggressive periodontitis is seen in
      young individual and mostly in females; majority of the patients of both groups
      belongs to low socioeconomic group. Body mass index which is a refection of
      nutritional status of an individual indicated that chronically energy defcient
      subjects in experimental group appeared to be higher. The average food and
      nutrient intake in control group was slightly better than that of experimental
      group. CONCLUSION: The diet survey indicated marginal and negligible defciencies
      in aggressive periodontitis patients compared to controls, and this coupled with
      chronically energy defciency as indicated by body mass index, calls for a
      detailed study of this aspect of aggressive periodontitis. The present study
      indicates that nutritional infuences point to a needle of suspicion toward the
      etiology of aggressive periodontitis.

PMID- 24685802
TI  - Developmental malformation of primary and permanent dentition: a rare sequel of
      trauma.
AB  - Dentofacial injuries that occur prior to the eruption of primary teeth can result
      in developmental disturbances not only in the primary but also in permanent
      dentition. Here we report a rare case of long term sequelae of trauma in a female
      child of 4 to 5 months of age which resulted in dilaceration and impaction of
      maxillary primary central incisors and subsequent enamel hypoplasia of the
      permanent maxillary central incisors.

PMID- 24685804
TI  - Pressure-induced alopecia from orthodontic headgear.
AB  - Every treatment in the dental specialty has its own set of complications,
      Orthodontic therapy being no exception. Such a problem during the course of
      treatment puts the specialist in a dilemma as to whether to continue or stop the
      treatment. One such case in which during headgear therapy, a rare complication
      such as alopecia was encountered has been dealt with in this paper. This case
      report shows its effective management while still continuing treatment, thus
      leading to the desired result. It emphasizes on the importance of maintaining a
      balance between the benefts and risks of a treatment. CLINICAL RELEVANCE: The use
      of headgear can lead to the rare complication of alopecia and the clinician
      should be aware of it. OBJECTIVE: The reader should understand the psychological
      implications of alopecia and also to carry out the treatment after assessing the
      risk/beneft ratio.

PMID- 24685801
TI  - Evaluation of malocclusion in MPDS.
AB  - INTRODUCTION: Myofascial pain dysfunction syndrome (MPDS) is a disorder which is
      characterized by facial pain and limited mandibular function because of the
      complex nature of this disease. Malocclusion was never evaluated in MPDS patients
      to know its role. Electromyographic silent period durations of masseter were used
      for objective assessment of MPDS patients. AIM: To evaluation of role of
      malocclusion in MPDS patients and also to study the EMG masseteric silent period
      pattern in MPDS patients in different malocclusions. MATERIALS AND METHODS: Two
      groups, groups I and II of 75 subjects each, were included in this study. Groups
      I and II constituted the normal subjects and MPDS patients respectively. All
      these subjects in both the groups were again subdivided based on Angle's class I,
      II and III malocclusion. Electromyographic (EMG) silent period of masseteric
      muscle on both sides was measured for all the subjects in both the groups to know
      whether it differs according to the type of malocclusion. RESULTS: The silent
      period was more in group II (MPDS patients). There was no signifcant difference
      in the silent periods in Angle's class I, II and III malocclusion in group I,
      whereas in group II, there was a signifcant difference in the silent period in
      Angle's class II compared to Angle's class I and III. There was no signifcant
      difference between males and females. CONCLUSION: MPDS patients are more in
      Angle's class I malocclusion. Silent period is more in Angle's class II
      malocclusion of MPDS group. CLINICAL SIGNIFCANCE: The EMG masseter silent period
      duration can be advantageously utilized as an adjunct to clinical examination for
      diagnosis of myofascial pain dysfunction syndrome. It is enough if one side
      masseter muscle is measured for silent period duration.

PMID- 24685803
TI  - A novel treatment of gingival recession using a botanical topical gingival patch
      and mouthrinse.
AB  - BACKGROUND AND AIM: Current treatment of gingival recession (GR) is limited to
      surgical procedures. We describe a case series of 18 patients with GR who were
      treated with a botanical patch and rinse following standard conservative therapy.
      CASE SERIES DESCRIPTION: A total of 22 sites with GR > 1 mm were studied.
      Following scaling and root planing (SRP) and oral hygiene instruction, patients
      received two courses of patch treatment (3 days each) and botanical rinse
      administered twice daily throughout the treatment period. Outcome measures (GR,
      gingival index (GI) and gingival thickness (GT) were taken at baseline; at 1 to 2
      weeks; 2 to 4 weeks; and at 6 to 8 weeks. Miller classifcation and plaque index
      (PI) were measured at baseline and at 6 to 8 weeks. At the end of the treatment
      period, mean GR decreased from 4.18 +/- 1.74 mm to 3.31 +/- 1.51 mm (20.8%);
      Miller grade from 1.86 +/- 0.56 to 1.06 +/- 0.43; GI scores from 1.45 +/- 0.63 to
      0.17 +/- 0.38 (88.3%); and PI scores from 1.33 +/- 0.59 to 0.78 +/- 0.94. GT
      increased from 0.74 mm +/- 0.40 to 1.21 +/- 0.39 (63.5%). No adverse effects were
      reported with either the patch or rinse treatments. CONCLUSION: We observed a
      decrease in GR and GI scores in 18 patients (22 sites) treated with the study
      patch and rinse, with increased GT. CLINICAL SIGNIFICANCE: A combined botanical
      patch-rinse treatment may be effective as adjuvant treatment to standard
      conservative care for GR. Further research is needed to verify these fndings.

PMID- 24685806
TI  - Impeded eruption of mandibular canine.
AB  - Odontome, tumor of odontogenic origin, is associated with disturbances in the
      eruption of teeth such as impaction, delayed eruption or retention of permanent
      teeth. It is seen on radiographic examination as a radiopaque lesion which may be
      single or multiple. Morphologically, odontomes are of two types-compound or
      complex and can be found at any age with high prevalence in maxilla than in
      mandible. In this case report, lack of eruption of permanent mandibular canine
      owing to presence of associated compound odontome is presented.

PMID- 24685807
TI  - Removal of a fractured locator abutment screw fragment.
AB  - BACKGROUND: Although, dental implants have been a predictable option to support
      several types of restorations, mechanical problems are not uncommon. Retaining
      and abutment screw loosenings/fractures are one of the most common technical
      problems. AIM: To present a step-by-step technique in order to remove a broken
      locater abutment screw fragment. MATERIALS AND METHODS: A 56-year-old, edentulous
      man with a fractured locator abutment screw in an implant was referred to our
      clinic from a private practice. His dentist placed a narrow platform locator
      abutment onto a regular platform implant and the fracture occurred. Attempts to
      remove the fractured fragment using a periodontal probe and a manual screw
      removal driver were unsuccessful. RESULTS: This clinical report presents a
      situation in which a fractured locater abutment screw fragment was successfully
      removed using an implant repair kit. CONCLUSION: A fractured locater abutment
      screw fragment was successfully removed using an implant repair kit including
      drills, drill guides and tapping instruments. To avoid similar complications, it
      is recommended to use appropriate manufacturer specified torque values in
      conjunction with compatible restorative components. CLINICAL SIGNIFICANCE:
      Retaining and abutment screw loosenings/fractures are one of the most common
      mechanical problems associated with the implant components. This clinical report
      showed how to remove a broken screw fragment using proper armamentarium and
      technique, which might help clinicians eliminate similar problems.

PMID- 24685809
TI  - Extra roots and root canals in premolar and molar teeth: review of an endodontic
      challenge.
AB  - The main goal of endodontic treatment is healing of the periapical tissues which
      are gained by elimination of bacteria and their byproducts from the canal and
      prevention from reinfection. Understanding of root canal anatomy is an essential
      part in endodontic treatment. Anatomic forms and variations in special teeth
      should be well known, one of them is extra roots/ canals. Although possible
      aberrations of canal anatomy should be considered for all teeth, some teeth
      should be highlighted. This review addresses the prevalence, diagnosis (clinical
      and radiographic), and endodontic management of teeth with extra roots/canals.

PMID- 24685805
TI  - The correction of maxillary defciency with internal distraction devices: a
      multidisciplinary approach.
AB  - AIM: The purpose of this case report is to present the orthodontic, surgical and
      restorative treatments in the case of an operated cleft lip and palate and severe
      maxillary defciency in a 14-year-old female patient. BACKGROUND: Only orthodontic
      treatment could be ineffcient for cleft lip and palate patients characterized
      with maxillary hypoplasia. Orthodontic and surgical treatment shows suffcient
      results, especially with severe skeletal defciency. CASE REPORT: A cleft lip and
      palate patient required complex multidisciplinary treatment to preserve health
      and restore esthetics. Dental leveling and alignment of the maxillary and
      mandibular teeth were provided before the surgery. Maxillary advancement and
      clockwise rotation of the maxillary-mandibular complex was applied by a Le Fort 1
      osteotomy with two internal distraction devices. After the active treatment
      including orthodontic treatment and orthognathic surgery, upper full mouth
      ceramic restoration was applied. CONCLUSION: This report shows the efficiency of
      internal distraction devices in cleft lip palate patients and exemplifes the
      multidisciplinary care required for such diffcult cases. Clinical signifcance:
      Stable improved occlusion and skeletal relations were observed after a follow-up
      examination period of 12 months.

PMID- 24685808
TI  - Utilization of different management concepts in fractured tooth fragment
      reattachment: a report of three cases.
AB  - Traumatic injuries of teeth involve varying degrees of damage to the supporting
      soft tissues or the teeth itself. A very common injury to the permanent dentition
      affecting children and adolescents during their growing years is the anterior
      crown fracture. Recent developments in restorative material, placement
      techniques, preparation designs, and an adhesive protocol allow clinicians to
      predictably restore fractured teeth. With the advent of adhesive dentistry the
      process of fragment reattachment has become simplifed and more reliable. This
      procedure provides an improved function, is relatively faster to perform and at
      the same time provides long lasting esthetics. This paper discusses various
      innovative techniques of fracture reattachment depending on the complexity of the
      case.

PMID- 24685810
TI  - The museum maze in oral pathology demystifed: part II.
AB  - Museum technology is perpetually changing due to current requirements and added
      inventions for our comfort and furbished display of specimens. Hence numerous
      methods of specimen preservation have been put on trial by diverse people in the
      medical feld as are the inventions. But only few have caught people's interest
      and are popularized today. This part provides unique insights into specialized
      custom-made techniques, evolution of recent advances like plastination and
      virtual museum that have popularized as visual delights. Plastination gives
      handy, perennial life-like acrylic specimens, whereas virtual museum takes museum
      feld to the electronic era making use of computers and virtual environment.

PMID- 24685811
TI  - Miniscrew implants as temporary anchorage devices in orthodontics: a
      comprehensive review.
AB  - In recent times, the use of miniscrew implants to obtain absolute anchorage has
      gained momentum in clinical orthodontics as rigid anchorage modality. Miniscrew
      implants offers many advantages when used as temporary anchorage devices like,
      easy placement and removal, immediate loading, can be used in a variety of
      locations, provide absolute anchorage, economic and requires less patient
      cooperation. This makes them as a necessary treatment option in cases with
      critical anchorage that would have otherwise resulted in anchorage loss if
      treated with conventional means of anchorage. The aim of this comprehensive
      review is to highlight the gradual evolution, clinical use, advantages and
      disadvantages of the miniscrew implants when used to obtain a temporary but
      absolute skeletal anchorage for orthodontic applications.

PMID- 24685812
TI  - Hemangioma: review of literature.
AB  - Hemangiomas are tumors identifed by rapid endothelial cell proliferation in early
      infancy, followed by involution over time. All other abnormalities are
      malformations resulting from anomalous development of vascular plexuses. The
      malformations have a normal endothelial cell growth cycle that affects the veins,
      the capillaries or the lymphatics and they do not involute. Hemangiomas are the
      most common tumors of infancy and are characterized by a proliferating and
      involuting phase. They are seen more commonly in whites than in blacks, more in
      females than in males in a ratio of 3:1.

PMID- 24685813
TI  - Retraction notice to: influence of post fit and post length on fracture
      resistance: an in vitro study. J Contemp Dent Pract 2013;14(3):496-500.
AB  - It has been notified to the Editorial Board, The Journal of Contemporary Dental
      Practice (JCDP), that considerable script of the aforementioned article has been
      plagiarized from the article: Buttel L, Krastl G, Lorch H, Naumann M, Zitzmann
      NU, Weiger R. Influence of Post Fit and Post Length on Fracture Resistance. Int
      Endod J 2009;42(1):47-53. The same was confirmed after thorough evaluation and
      interpretation. In accordance to observe serious view in case of plagiarism, the
      Editorial Board, JCDP decided to take appropriate action against the act. Thus,
      it is herewith decided by the Editorial Board, JCDP to retract the title as
      addressed from the assigned issue. 

PMID- 24685814
TI  - Editorial. Oral submucous fibrosis: revised hypotheses as to its cause.
AB  - Oral submucous fbrosis (OSF), being a prototype of pathological fbrosis, remains
      enigmatic as regards its causation. The connective tissue production is permanent
      and there is no reversal of the condition even after cessation of the habit of
      areca-nut usage; prime suspect in its causation.(1) The bulk of the connective
      tissue consists of type-1 collagen(2) and its formation does not appears to be
      caused by excessive proliferation of fbroblasts.(3) The effect of areca nut
      extract on in vitro fbroblasts varies on a concentration gradient, predominantly
      suppressing rather than stimulating the growth of the cells.(4) Based on
      morphological characteristics, the fbroblast population in the diseased mucosa
      has been classifed in to types F1, F2 and F3 with F3 cells producing signifcantly
      more collagen than the other two cell types. It was concluded that a change of
      fbroblast population has occurred in OSF and that this relative increase of F3
      cells in humans, could be committed to the production of large quantities of
      collagen formation in OSF. It has been proposed that fbroblasts are functionally
      heterogeneous, the composition of any given normal or diseased connective tissue
      being a consequence in part of its particular mixture of fbroblast subtypes and
      density. Subtype deletion or amplifcation can result from selective cytotoxic or
      mitogenic responses induced by the binding environmental ligands.(5) Against this
      backdrop, we propose few de-novo attributes, hitherto unreported, and seem to be
      of relevance in the pathogenesis of OSF; namely the role of autophagy in basic
      cellular homeostatic process, important to cell fate decisions under conditions
      of stress and also ECM producing cells (fbroblasts, myofbroblasts and smooth
      muscle cells) derived from epithelial and endothelial cells through process
      termed epithelial and endothelial-mesenchymal transition. 

PMID- 24685816
TI  - Impact of multivessel disease on infarct size among STEMI patients undergoing
      primary angioplasty.
AB  - BACKGROUND: Although primary angioplasty achieves Thrombolysis In Myocardial
      Infarction (TIMI) 3 flow in most patients with ST-elevation myocardial
      infarction, epicardial recanalization does not guarantee optimal perfusion in a
      large proportion of patients. Multivessel disease has been demonstrated to be
      associated with impaired survival, however its impact on infarct size has not
      been largely investigated, that therefore is the aim of the current study.
      METHODS: Our population is represented by 827 STEMI patients undergoing primary
      PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi. RESULTS:
      Multivessel disease was observed in 343 patients (41.5%). It was associated with
      older age (65 [57-74] vs 63 [53-71], p < 0.001), higher rate of previous MI (6.4%
      vs 2.5%, p = 0.005), longer ischemia time evaluated as continuous variable (210
      [155-280] min vs 196 [145-270] min, p = 0.065) or percentage of patients with
      ischemia time >3 h (63.7% vs 56.4%, p = 0.038), and a trend in more cardiogenic
      shock (5.5% vs 2.9%, p = 0.055). Patients with multivessel disease received more
      often Abciximab (92.1% vs 88.4%, p < 0.001), Intra-aortic balloon pump (6.4% vs
      1.9%, p < 0.001). No differences were observed in other clinical or angiographic
      characteristics. In particular, multivessel disease did not affect the rate of
      postprocedural TIMI 3 flow (90.9% vs 93.4%, p = 0.18) and ST-segment resolution
      (52.4% vs 54.9%, p = 0.48). Multivessel disease did not affect infarct size
      (12.7% [4.5%-24.9%] vs 12.3% [4%-24.1%], p = 0.58). Similar results were observed
      in subanalyses without any significant interaction for each variable (anterior
      infarct location (p int = 0.23), gender (p int = 0.9), age (p int = 0.7),
      diabetes (p int = 0.15)). The absence of any impact of multivessel disease on
      infarct size was confirmed when the analysis was conducted according to the
      percentage of patients with infarct size above the median, even after correction
      for baseline characteristics, such as age, previous MI, ischemia time, use of Gp
      IIb-IIIa inhibitors, cardiogenic shock, ischemia time (OR [95% CI] = 1.09 [0.82
      1.45], p = 0.58). CONCLUSIONS: This study shows that among STEMI patients
      undergoing primary PCI multivessel disease does not affect infarct size.

PMID- 24685815
TI  - Targeted mouse complement inhibitor CR2-Crry protects against the development of
      atherosclerosis in mice.
AB  - OBJECTIVE: Atherosclerosis is a chronic inflammatory and immune vascular disease,
      and clinical and experimental evidence has indicated an important role of
      complement activation products, including the terminal membrane attack complex
      (MAC), in atherogenesis. Here, we investigated whether complement inhibition
      represents a potential therapeutic strategy to treat/prevent atherogenesis using
      CR2-Crry, a recently described complement inhibitor that specifically targets to
      sites of C3 activation. METHODS AND RESULTS: Previous studies demonstrated that
      loss of CD59 (a membrane inhibitor of MAC formation) accelerated atherogenesis in
      Apoe deficient (Apoe(-/-)) mice. Here, both CD59 sufficient and CD59 deficient
      mice in an Apoe deficient background (namely, mCd59 ab(+/+)/Apoe(-/-) and mCd59
      ab(-/-)/Apoe(-/-)) were treated with CR2-Crry for 4 and 2 months respectively,
      while maintained on a high fat diet. Compared to control treatment, CR2-Crry
      treatment resulted in significantly fewer atherosclerotic lesions in the aorta
      and aortic root, and inhibited the accelerated atherogenesis seen in mCd59
      ab(+/+)/Apoe(-/-) and mCd59 ab(-/-)/Apoe(-/-) mice. CR2-Crry treatment also
      resulted in significantly reduced C3 and MAC deposition in the vasculature of
      both mice, as well as a significant reduction in the number of infiltrating
      macrophages and T cells. CONCLUSION: The data demonstrate the therapeutic
      potential of targeted complement inhibition.

PMID- 24685817
TI  - Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in
      patients with stable coronary disease on statin treatment.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator
      of LDL-cholesterol receptor homeostasis and emerges as a therapeutic target in
      the prevention of cardiovascular (CV) disease. This prospective cohort study
      analyzes risk prediction with PCSK9 serum concentrations in patients with stable
      coronary artery disease (CAD) on statin treatment. METHODS AND RESULTS: Fasting
      PCSK9 concentrations were measured in 504 consecutive patients with stable CAD
      confirmed by angiography. Oral glucose tolerance tests were performed in all
      patients without known diabetes. Patients were followed up for 48months. The
      primary outcome was the composite of cardiovascular death and unplanned
      cardiovascular hospitalization. Serum concentrations of PCSK9 predicted CV
      outcomes (PCSK9>622 ng/ml vs. <471 ng/ml: HR 1.55, 95%-CI 1.11-2.16, p=0.009).
      Higher PCSK9 concentrations were associated with female gender, hypertension,
      statin treatment, C-reactive protein, HbA1c, insulin, total cholesterol and
      fasting triglycerides, but not with LDL- or HDL-cholesterol. The association of
      PCSK9 levels with CV events was reduced after adjustment for fasting TG.
      CONCLUSION: PCSK9 concentrations predict cardiovascular events in patients with
      coronary artery disease on statin treatment. Serum triglycerides are correlated
      with PCSK9 and modify risk prediction by PCSK9.

PMID- 24685818
TI  - Stimulation of alpha7 nicotinic acetylcholine receptor by AR-R17779 suppresses
      atherosclerosis and aortic aneurysm formation in apolipoprotein E-deficient mice.
AB  - Atherosclerosis is a chronic inflammatory disease. It has been appreciated that
      vagus nerve inhibits macrophage activation via alpha7 nicotinic acetylcholine
      receptor (nAChR), termed the cholinergic anti-inflammatory pathway. We explored
      the effects of AR-R17779, a selective alpha7nAChR agonist, on atherosclerosis and
      aneurysm formation in apolipoprotein E (ApoE)-deficient mice. ApoE-deficient mice
      were fed a high-fat diet (HFD) and angiotensin II (Ang II) was infused by osmotic
      minipumps from 10-week-old for 4weeks. AR-R17779 was given in drinking water ad
      libitum. Oil red O staining of the aorta showed that combined loading of HFD and
      Ang II induced marked atherosclerosis compared with control mice fed a normal
      chow. Treatment with AR-R17779 significantly reduced atherosclerotic plaque area
      and improved survival of mice. Treatment with AR-R17779 also suppressed abdominal
      aortic aneurysm formation. Quantitative RT-PCR of the aorta revealed that mRNA
      expression levels of interleukin-1beta, interleukin-6 and NOX2 were significantly
      decreased in AR-R17779-treated mice compared with Ang II+HFD mice. AR-R17779
      treatment also reduced blood pressure and serum lipid levels. In conclusion,
      alpha7nAChR activation attenuates atherogenesis and aortic abdominal aneurysm
      formation in ApoE-deficient mice possibly through an anti-inflammatory effect and
      reduction of blood pressure and lipid levels. Pharmacological activation of
      alpha7nAChR may have a therapeutic potential against atherosclerotic vascular
      diseases through multiple mechanisms. 

PMID- 24685819
TI  - Endothelium-independent hypoxic contraction of porcine coronary arteries may be
      mediated by activation of phosphoinositide 3-kinase/Akt pathway.
AB  - Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway plays an essential role in
      the regulation of vascular tone. The present study aimed to determine its role in
      hypoxic coronary vasoconstriction. Isometric tension of isolated porcine coronary
      arteries was measured with organ chamber technique; the protein levels of
      phosphorylated and total MLC were examined by Western blotting; the activities of
      PI3K and Rho kinase were determined by the phosphorylation of their respective
      target protein Akt and MTPT1. Acute hypoxia induced a rapid contraction followed
      by a short-term relaxation and then a sustained contraction in porcine coronary
      arteries. The rapid but not the sustained contraction was abolished by
      endothelium removal. The sustained contraction was attenuated by inhibitors of
      PI3K (LY294002) and Akt (Akt-I). The attenuation effect caused by LY294002 was
      not affected by nifedipine, but was abolished by Y27632, an inhibitor of Rho
      kinase. The sustained hypoxic contraction was associated with altered
      phosphorylation of MLC and Akt, which was inhibited by LY294002. The sustained
      hypoxic contraction was also accompanied with increased phosphorylation of MYPT1,
      which was inhibited by LY294002 and Y27632. This study demonstrates that
      sustained hypoxia causes porcine coronary artery to contract in an endothelium
      independent manner. An increased PI3K/Akt/Rho kinase signaling may be involved. 

PMID- 24685822
TI  - Cannabis abuse and age at onset in schizophrenia patients with large, rare copy
      number variants.
AB  - BACKGROUND: Large deletions are found to a greater extent in patients with
      schizophrenia compared with healthy controls. This study aims to investigate
      clinical symptomatology and substance abuse rates in patients with large
      (>500kb), rare (<1% of cohort) deletions and duplications compared with
      schizophrenia patients in general. METHODS: 633 schizophrenia patients, including
      60 with large (>500kb), rare (<1% of cohort) deletions and 74 with large, rare
      duplications, who formed part of a large genome-wide association study, were
      assessed for alcohol and cannabis abuse rates as well as a range of symptom
      measures using the Diagnostic Interview for Genetic Studies (DIGS), Family
      Interview for Genetic Studies (FIGS), and medical records. RESULTS: Patients with
      large, rare deletions had significantly less cannabis abuse rates but comparable
      alcohol abuse rates, with an age at onset later than those without large, rare
      deletions. There was no significant difference in any substance abuse or clinical
      symptom rates between patients with and without large, rare duplications, but an
      interaction did exist between cannabis abuse, duplication status, and age at
      onset, with cannabis abuse resulting in an earlier age at onset only in those
      without a large, rare duplication. Similarly, patients with a large, rare
      duplication had a later onset age for cannabis abuse/dependence. CONCLUSIONS:
      Schizophrenia patients with large, rare deletions were less likely to have
      comorbid cannabis abuse over their lifetime. This provides support for a
      threshold model of risk with those carrying a schizophrenia-associated copy
      number variation less reliant on environmental insults. Patients with large, rare
      duplications were protected against earlier onset of schizophrenia in the
      presence of comorbid cannabis abuse in addition to later onset of cannabis abuse
      itself.

PMID- 24685820
TI  - Immunologic status and virologic outcomes in repeat pregnancies to HIV-positive
      women not on antiretroviral therapy at conception: a case for lifelong
      antiretroviral therapy?
AB  - During their second pregnancy with diagnosed HIV (n = 1177), two-fifths of women
      in the UK/Ireland not on antiretroviral therapy (ART) at conception had an
      immunological indication for treatment (CD4(+) <350 cells/MUl), of whom nearly
      half had CD4(+) at least 350 cells/MUl in their previous pregnancy. Those
      initiating ART during pregnancy had a 4.3-fold increased odds of detectable viral
      load at delivery compared with those conceiving on treatment, suggesting that
      continuation of ART after pregnancy may be beneficial for many women.

PMID- 24685821
TI  - Disparities in psychosocial functioning in a diverse sample of adults with
      anxiety disorders.
AB  - Anxiety disorders are associated with psychosocial functional impairments, but no
      study has compared how these impairments might vary by ethno-racial status. We
      examined whether minority status was uniquely associated with functional
      impairments in 431 adults with anxiety disorders. Functioning was measured in the
      rater-assessed domains of: Global Assessment of Functioning (GAF); global
      psychosocial functioning; work, relationship, and recreational functioning; and,
      self-reported: life satisfaction, mental health functioning, physical
      functioning, and disability status. After controlling for demographic and
      clinical variables, results revealed evidence of disparities, whereby African
      Americans (AAs), particularly those with low income, had worse GAF, worse global
      psychosocial functioning, and were more likely to be disabled compared to non
      Latino Whites. Latinos, particularly those with low income, had worse global
      psychosocial functioning than non-Latino Whites. Results suggest AAs and Latinos
      are at increased risk for functional impairments not better accounted for by
      other demographic or clinical variables.

PMID- 24685823
TI  - Schizophrenia and co-occurring substance use disorder: reward, olfaction and
      clozapine.
AB  - Co-occurring substance use disorders (SUD), including alcohol, are common in
      schizophrenia (SZ) and are associated with poor outcome. Emerging data suggest
      that individuals with SZ have a dysfunctional brain reward circuit that may
      underlie their frequent use of alcohol and other substances, and further, that
      the atypical antipsychotic, clozapine (CLOZ), limits alcohol/substance use in
      these individuals, potentially by ameliorating this brain reward circuit
      dysfunction. To explore this hypothesis, reward functioning in a SZ sample with a
      history of co-occurring SUD, treated with either CLOZ (n=13) or typical
      antipsychotic agents (TYP), haloperidol or fluphenazine (n=14), as well as
      healthy controls (n=16), was evaluated through ratings of pleasurable and
      aversive odors, stimuli that are processed by several neural structures thought
      to play a key role in processing rewarding stimuli. Results suggest that CLOZ
      treatment is associated with broadening and strengthening the hedonic experience
      of these rewarding olfactory stimuli, both of a pleasant and unpleasant nature.
      This hedonic appraisal of odors appeared to be independent of odor perception
      (intensity ratings) and clinical symptoms. These preliminary findings provide
      important new data in support of the hypothesis that CLOZ ameliorates some
      aspects of abnormal brain reward functioning in individuals with co-occurring SZ
      and SUD. Further research may have valuable treatment implications for this
      population including interventions for other reward-associated deficits in
      learning, social interactions and other aspects of behavior and cognition. 

PMID- 24685824
TI  - Anti-fatigue and vasoprotective effects of quercetin-3-O-gentiobiose on oxidative
      stress and vascular endothelial dysfunction induced by endurance swimming in
      rats.
AB  - Chronic fatigue accumulation increases the incidence of cardiovascular disease
      while the treatment of antioxidants could prevent this development. We have
      previously shown that quercetin-3-O-gentiobiose (QG), a flavonoid isolated from
      tonic herb Okra, possesses anti-oxidative properties. In the present study, the
      protective effects of QG were evaluated in a rat model of load-induced endurance
      swimming. Oral administration of QG at the doses of 25-75mg/kg could
      significantly improve the endurance capability of rats to fatigue along with
      decrease serum lactic acid and blood urea nitrogen levels were decreased.
      Moreover, QG could alleviate vascular impairments, enhance the activities of
      antioxidant enzymes and attenuate the levels of inflammatory cytokines (MCP-1, IL
      6 and TNF-alpha). The results indicated that QG had anti-fatigue and
      vasoprotective effects and represented a potential agent for the treatment of
      aortic pathology involved with fatigue- and related syndrome. 

PMID- 24685826
TI  - Oral exposure of Kunming mice to diisononyl phthalate induces hepatic and renal
      tissue injury through the accumulation of ROS. Protective effect of melatonin.
AB  - Diisononyl phthalate (DINP) has been widely used in polyvinyl chloride (PVC)
      products and is ubiquitous as a substitute; however, its toxicity due to exposure
      remains to be determined. This study investigated the oxidative damage induced by
      DINP and the induced production of the pro-inflammation cytokines interleukin-1
      (IL-1) and tumour necrosis factor-alpha (TNF-alpha). Oral exposure to DINP
      induced oxidative damage and inflammatory responses in liver and kidney tissues
      through the accumulation of ROS, which may be an underlying mechanism for its
      toxicity. These changes may contribute to hepatic and renal histopathological
      alterations. Our data suggest that oxidative stress is involved in DINP-induced
      toxicity and that the co-administration of melatonin exerts a protective effect
      against DINP-induced toxicity. 

PMID- 24685825
TI  - Galla rhois exerts its antiplatelet effect by suppressing ERK1/2 and PLCbeta
      phosphorylation.
AB  - Galla rhois and its components have various biological activities, including
      protective effects on liver cells as well as antimetastatic, antiplatelet, and
      antibacterial effects. In the present study, we identified the antiplatelet
      activity and possible mechanism of action of a G. rhois extract (GRE). We
      investigated the effect of GRE and its components on rabbit platelet activation,
      and their possible molecular mechanisms. The GRE inhibited collagen-, AA-, and
      thrombin-induced platelet aggregation as well as serotonin secretion, in a
      concentration-dependent manner. The GRE significantly inhibited the production of
      lipoxygenase-mediated 12-hydroxyeicosatetraenoic acid. The GRE effectively
      suppressed thrombin-stimulated PLCbeta3 phosphorylation and collagen-induced
      ERK1/2 phosphorylation, in addition, the GRE significantly restored the cAMP
      level, which had decreased due to collagen or thrombin. Among the components of
      GRE, methyl gallate inhibited the collagen-induced platelet activation through
      suppression of ERK phosphorylation, penta-O-galloyl-beta-D-glucoside inhibited
      the thrombin-induced platelet activation through suppression of PLCbeta
      phosphorylation. These results indicate that the GRE including methyl gallate and
      penta-O-galloyl-beta-D-glucoside suppressed platelet activation by inhibiting
      ERK1/2 and PLCbeta3 phosphorylation.

PMID- 24685827
TI  - Assessment of the early predictive power of quantitative magnetic resonance
      imaging parameters during neoadjuvant chemotherapy for uterine cervical cancer.
AB  - OBJECTIVES: The purpose of this study was to quantitatively evaluate 3 types of
      magnetic resonance imaging (MRI) parameters in parallel for the early prediction
      of neoadjuvant chemotherapy (NACT) effectiveness in cervical cancer-tumor volume
      parameters, diffusion parameters, and perfusion parameters. MATERIALS AND
      METHODS: We prospectively evaluated 13 patients with International Federation of
      Gynecology and Obstetrics stage IB to IIB cervical squamous cell carcinoma who
      underwent 3 serial MRI studies, that is, pretreatment, post-first course NACT,
      and post-second course NACT followed by radical hysterectomy. We obtained tumor
      volume parameters, diffusion parameters, and dynamic contrast material-enhanced
      perfusion parameters quantitatively from pretreatment MRI and post-first course
      MRI. The correlation of these parameters and the eventual tumor volume regression
      rate (TVRR) obtained from pretreatment MRI and post-second course MRI before
      surgery were investigated, statistically based on the Pearson correlation
      coefficient. RESULTS: Thirteen patients had a total of 39 scans. Early TVRR (r =
      0.844; P < 0.001), the fractional volume of the tissue extracellular
      extravascular space (Ve, r = 0.648; P < 0.05), and the change of Ve during the
      first course of NACT (r = -0.638; P < 0.05) correlated with eventual TVRR.
      CONCLUSIONS: Early TVRR, Ve, and the change of Ve could be useful predictors for
      the treatment effectiveness of NACT. These parameters could help to modify
      strategy in the early stage of NACT and to choose individualized treatment to
      avoid the delay of radical treatment, even when NACT is ineffective.

PMID- 24685828
TI  - Pelvic exenteration for recurrent endometrial adenocarcinoma: a retrospective
      multi-institutional study about 21 patients.
AB  - OBJECTIVE: The aim of our study was to evaluate morbidity, mortality, and long
      term survival of patients who underwent pelvic exenteration (PE) with curative
      intent for recurrence of endometrial adenocarcinoma during a single decade.
      METHODS: We defined a cohort of 21 patients who met our inclusion criteria,
      referred to 4 cooperating gynecologic oncology settings in Germany and Italy
      between 2000 and 2011. Data regarding surgery, histology, and oncologic outcomes
      were collected and statistically evaluated. Survival was determined from the day
      of exenteration until the last follow-up or death. RESULTS: The median age was 66
      years. A total of 42.9% of the patients had major complications, and a complete
      resection was achieved in 85.7% of the patients. A total of 71.4% of the patients
      had negative nodes. No patient died intraoperatively. The perioperative
      mortality, calculated within 30 days from PE, was 4.8%. The overall 5-year
      survival rate, evaluated using the Kaplan-Meier method, was 40%. For the subgroup
      with complete resection and negative lymph nodes, overall survival reached 60%.
      CONCLUSIONS: Despite a high complication rate, PE for solitary pelvic recurrence
      of endometrial cancer yields a high rate of long-term survival.

PMID- 24685830
TI  - Core business, future direction, and the 10-bar target.

PMID- 24685831
TI  - Tipping points in ecological networks.
AB  - Network studies have described the complex interactions among species.
      Concomitantly, researchers have searched for signals of ecosystem tipping points
      and attributes of systems that resist them. A recent study combines these areas,
      showing that attributes of pollination network structure delay critical
      transitions, and generating a wealth of new research questions. 

PMID- 24685829
TI  - Incidence of central nervous system metastases in patients with HER2-positive
      metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel:
      results from the randomized phase III study CLEOPATRA.
AB  - BACKGROUND: Results from the phase III trial CLEOPATRA in human epidermal growth
      factor receptor 2-positive first-line metastatic breast cancer demonstrated
      significant improvements in progression-free and overall survival with
      pertuzumab, trastuzumab, and docetaxel over placebo, trastuzumab, and docetaxel.
      We carried out exploratory analyses of the incidence and time to development of
      central nervous system (CNS) metastases in patients from CLEOPATRA. PATIENTS AND
      METHODS: Patients received pertuzumab/placebo: 840 mg in cycle 1, then 420 mg;
      trastuzumab: 8 mg/kg in cycle 1, then 6 mg/kg; docetaxel: initiated at 75
      mg/m(2). Study drugs were administered i.v. every 3 weeks. The log-rank test was
      used for between-arm comparisons of time to CNS metastases as first site of
      disease progression and overall survival in patients with CNS metastases as first
      site of disease progression. The Kaplan-Meier approach was used to estimate
      median time to CNS metastases as first site of disease progression and median
      overall survival. RESULTS: The incidence of CNS metastases as first site of
      disease progression was similar between arms; placebo arm: 51 of 406 (12.6%),
      pertuzumab arm: 55 of 402 (13.7%). Median time to development of CNS metastases
      as first site of disease progression was 11.9 months in the placebo arm and 15.0
      months in the pertuzumab arm; hazard ratio (HR) = 0.58, 95% confidence interval
      (CI) 0.39-0.85, P = 0.0049. Overall survival in patients who developed CNS
      metastases as first site of disease progression showed a trend in favor of
      pertuzumab, trastuzumab, and docetaxel; HR = 0.66, 95% CI 0.39-1.11. Median
      overall survival was 26.3 versus 34.4 months in the placebo and pertuzumab arms,
      respectively. Treatment comparison of the survival curves was not statistically
      significant for the log-rank test (P = 0.1139), but significant for the Wilcoxon
      test (P = 0.0449). CONCLUSIONS: While the incidence of CNS metastases was similar
      between arms, our results suggest that pertuzumab, trastuzumab, and docetaxel
      delays the onset of CNS disease compared with placebo, trastuzumab, and
      docetaxel. CLINICALTRIALSGOV: NCT00567190.

PMID- 24685835
TI  - Reproducibility studies for experimental epitope detection in macrophages (EDIM).
AB  - INTRODUCTION: We have recently described epitope detection in macrophages (EDIM)
      by flow cytometry. This is a promising tool for the diagnosis and follow-up of
      malignancies. However, biological and technical validation is warranted before
      clinical applicability can be explored. METHODS: The pre-analytic and analytic
      phases were investigated. Five different aspects were assessed: blood sample
      stability, intra-individual variability in healthy persons, intra-assay
      variation, inter-assay variation and assay transferability. The post-analytic
      phase was already partly standardized and described in an earlier study. RESULTS:
      The outcomes in the pre-analytic phase showed that samples are stable for 24h
      after venipuncture. Biological variation over time was similar to that of serum
      tumor marker assays; each patient has a baseline value. Intra-assay variation
      showed good reproducibility, while inter-assay variation showed reproducibility
      similar to that of to established serum tumor marker assays. Furthermore, the
      assay showed excellent transferability between analyzers. CONCLUSION: Under
      optimal analytic conditions the EDIM method is technically stable, reproducible
      and transferable. Biological variation over time needs further assessment in
      future work.

PMID- 24685834
TI  - Using fluorescence correlation spectroscopy (FCS) for IFN-g detection: a
      preliminary study.
AB  - Nowadays, enzyme-linked immunosorbent assay (ELISA) based detection of
      Mycobacterium tuberculosis (M. tuberculosis) antigen triggered interferon-gamma
      (IFN-g) secretion by blood T cells displays an improved diagnostic value for M.
      tuberculosis infection. Applications of fluorescence correlation spectroscopy
      (FCS) have been explored in various subfields of medicine and molecular biology,
      including detection of a certain biomarker in liquid instead of ELISA. Here, we
      present a preliminary study of detecting IFN-g using FCS-based technique. 

PMID- 24685832
TI  - Racial differences in gestational weight gain and pregnancy-related hypertension.
AB  - PURPOSE: The aim of the study was to examine racial differences in gestational
      weight gain (GWG) and pregnancy-related hypertension. METHODS: Logistic
      regression models tested racial differences in adequacy of GWG and pregnancy
      induced hypertension in all singleton live births from the South Carolina 2004
      2006 birth certificates. RESULTS: Compared with white women, black and Hispanic
      women had 16%-46% lower odds of gaining weight above the recommendations.
      However, the odds of inadequate GWG was ~50% higher in black and Hispanic women
      with a pregnancy body mass index (BMI) less than 25 kg/m(2). Furthermore,
      compared with women with adequate GWG, women with excessive GWG had higher odds
      of pregnancy-related hypertension (underweight: 2.35, 95% confidence interval
      [CI; 1.66, 3.32]; normal: 2.05, 95% CI [1.84, 2.27]; overweight: 1.93, 95% CI
      [1.64, 2.27]; obese: 1.46, 95% CI [1.30, 1.63]). Among women with a BMI less than
      25 kg/m(2), black women had higher odds of pregnancy-related hypertension than
      white women (underweight: 1.64, 95% CI [1.14, 2.36]; normal weight: 1.28, 95% CI
      [1.15, 1.42]), whereas among women with a BMI less than 25 kg/m(2), Hispanic
      women had 40% lower odds. CONCLUSIONS: Programs are needed to curb excessive GWG
      in all racial groups and to help some sub-groups ensure adequate GWG. Maternal
      obesity and GWG are two factors that should be used in combination to reduce
      racial differences in pregnancy-related hypertension.

PMID- 24685838
TI  - A review of analytical methods for eicosanoids in brain tissue.
AB  - Eicosanoids are potent lipid mediators of inflammation and are known to play an
      important role in numerous pathophysiological processes. Furthermore,
      inflammation has been proven to be a mediator of diseases such as hypertension,
      atherosclerosis, Alzheimer's disease, cancer and rheumatoid arthritis. Hence,
      these lipid mediators have gained significant attention in recent years. This
      review focuses on chromatographic and mass spectrometric methods that have been
      used to analyze arachidonic acid and its metabolites in brain tissue. Recently
      published analytical methods such as LC-MS/MS and GC-MS/MS are discussed and
      compared in terms of limit of quantitation and sample preparation procedures,
      including solid phase extraction and derivatization. Analytical challenges are
      also highlighted. 

PMID- 24685836
TI  - Long-term improvement of speech perception with the fine structure processing
      coding strategy in cochlear implants.
AB  - AIMS: To investigate the long-term effects of the fine structure processing (FSP)
      coding strategy on speech perception in noise and quality of life in experienced
      cochlear implant (CI) users. METHODS: In a prospective comparative clinical
      trial, 32 experienced postlingually deafened CI recipients were upgraded from the
      Tempo+ to the Opus 2 audio processor, implementing FSP in one group and high
      definition continuous interleaved sampling (HDCIS) coding strategy in another
      group with identical frequency ranges. Speech perception in noise testing and the
      Speech, Spatial and Qualities (SSQ) questionnaire were administered at 0, 6, 12
      and 24 months after the upgrade. RESULTS: FSP yielded significant long-term
      improvement of speech perception in noise of in total 13.2 dB from 16.2 dB SNR at
      the upgrade to 3.0 dB SNR after 24 months of FSP experience. No significant
      improvement of speech perception in noise over time was measured for the HDCIS
      group. With the SSQ questionnaire, a significant benefit of the FSP coding
      strategy was observed. CONCLUSIONS: The FSP coding strategy as implemented in the
      Med-EL Opus 2 audio processor improves speech perception in noise. This
      beneficial effect of FSP on speech perception in noise is not immediate but is
      significant after 12 months and further improves up to 24 months after
      implementation of FSP.

PMID- 24685839
TI  - Analysis, physiological and clinical significance of 12-HETE: a neglected
      platelet-derived 12-lipoxygenase product.
AB  - While the importance of cyclooxygenase (COX) in platelet function has been amply
      elucidated, the identification of the role of 12-lipoxygenase (12-LOX) and of its
      stable metabolite, 12-hydroxyeicosatretraenoic acid (12-HETE), has not been
      clarified as yet. Many studies have analysed the implications of 12-LOX products
      in different pathological disorders but the information obtained from these works
      is controversial. Several analytical methods have been developed over the years
      to simultaneously detect eicosanoids, and specifically 12-HETE, in different
      biological matrices, essentially enzyme-linked immunosorbent assays (ELISA),
      radioimmunoassays (RIA), high performance liquid chromatography (HPLC) and mass
      spectrometry coupled with both gas and liquid chromatography methods (GC- and LC
      MS). This review is aimed at summarizing the up to now known physiological and
      clinical features of 12-HETE together with the analytical methods used for its
      determination, focusing on the critical issues regarding its measurement. 

PMID- 24685833
TI  - The External Quality Assurance Oversight Laboratory (EQAPOL) proficiency program
      for IFN-gamma enzyme-linked immunospot (IFN-gamma ELISpot) assay.
AB  - The interferon-gamma enzyme-linked immunospot (IFN-gamma ELISpot) assay has been
      developed and used as an end-point assay in clinical trials for infectious
      diseases and cancer to detect the magnitude of antigen-specific immune responses.
      The ability to compare data generated by different laboratories across
      organizations is pivotal to understand the relative potency of different
      therapeutic and vaccine strategies. We developed an external proficiency program
      for the IFN-gamma ELISpot assay that evaluates laboratory performance based on
      five parameters: timeliness for data reporting; ability to handle cellular
      samples; detection of background (non-specific) responses; accuracy to consensus
      of the results; and precision of the measurements. Points are awarded for each
      criterion, and the sum of the points is used to determine a numeric and
      adjectival performance rating. Importantly, the evaluation of the accuracy to the
      consensus mean for the detection of antigen-specific responses using laboratory
      specific procedures informs each laboratory and its sponsor on the degree of
      concordance of its results with those obtained by other laboratories. This study
      will ultimately provide the scientific community with information on how to
      organize and implement an external proficiency program to evaluate longitudinally
      the performance of the participating laboratories and, therefore, fulfill the
      requirements of the GCLP guidelines for laboratories performing end-point IFN
      gamma ELISpot assay for clinical trials. 

PMID- 24685837
TI  - Priapism in homozygous sickle cell patients: important clinical and laboratory
      associations.
AB  - OBJECTIVE: To evaluate the relationship between the occurrence of priapism and
      important steady-state clinical and laboratory parameters in homozygous sickle
      cell disease (SCD). SUBJECTS AND METHODS: Steady-state clinical and laboratory
      data were obtained from the medical records of 126 male patients seen in the
      clinic over a 7-year period. Estimated prevalence rates, correlation coefficients
      and independent t tests were calculated to assess the relationship between
      priapism and several important clinical and laboratory indices. Patient data on
      age, haemoglobin concentrations, the frequency of crises per annum, leucocyte
      counts, platelet counts, serum bilirubin and aspartate transaminase were
      evaluated. RESULTS: The prevalence of priapism was determined to be 21.4%, and
      22.2% of those affected had erectile dysfunction. There was a significant
      positive correlation between priapism and older age (p = 0.049) and lower
      leucocyte counts (p = 0.008). There was no significant relationship with other
      clinical or laboratory indices. CONCLUSION: About 1 in 4 of all homozygous older
      SCD patients had priapism, and an approximately similar ratio developed erectile
      dysfunction; they also had lower steady-state leucocyte counts. Other clinical
      and laboratory indicators of disease severity in SCD did not positively correlate
      with the occurrence of priapism, and this may imply an alternative pathogenetic
      mechanism.

PMID- 24685843
TI  - Streamlining advertisements: editorial perspective.

PMID- 24685840
TI  - Cognitive and affective dysfunctions in autoimmune thyroiditis.
AB  - Hashimoto's thyroiditis (HT) is the most frequent cause of hypothyroidism in
      areas with sufficient iodine intake. While the impact of thyroid function on mood
      and cognition is well known, only in the recent years, an increasing number of
      studies report on the association of HT with cognitive and affective disturbances
      also in the euthyroid state. Recent imaging studies have shown that these
      impairments are accompanied by altered brain perfusion, in particular, in the
      frontal lobe and a reduced gray matter density in the left inferior gyrus
      frontalis. Brain function abnormalities in euthyroid patients with HT may be
      subtle and only detected by specific testing or even severe as it is the case in
      the rare neuropsychiatric disorder Hashimoto's encephalopathy (HE). The good
      response to glucocorticoids in patients with HE indicates an autoimmune origin.
      In line with this, the cognitive deficits and the high psycho-social burden in
      euthyroid HT patients without apparent signs of encephalopathy appear to be
      associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in
      vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to
      a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in
      HT patients, TPO Abs may function only as a marker of an autoimmune disorder of
      the central nervous system. In line with this, anti-central nervous system auto
      antibodies (CNS Abs) which are markedly increased in patients with HT disturb
      myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In
      addition, in HT patients, production of monocyte- and T-lymphocyte-derived
      cytokines is also markedly increased which may negatively affect multiple
      neurotransmitters and, consequently, diverse brain neurocircuits. 

PMID- 24685841
TI  - Family and Community Influences on Diabetes-Related Dietary Change in a Low
      Income Urban Neighborhood.
AB  - PURPOSE: The purpose of this study is to explore the influence of the social
      environment, including family and community relationships, on diabetes-related
      dietary change behaviors in a low-income, predominantly African American
      community with limited access to healthy foods. METHODS: Study methods included
      interviews and focus groups with adults with diabetes and family members of
      individuals with diabetes in a low-income African American community. In this
      analysis, interview participants included 11 participants with diabetes, one with
      prediabetes, and 8 family members or close friends with diabetes. Information
      from 4 participants with diabetes and 6 with family members with diabetes was
      included from 6 focus groups. Transcripts were analyzed via thematic iterative
      coding influenced by social cognitive theory to understand the influence of
      family and community relationships on dietary change. RESULTS: Participants'
      social environments strongly influenced diet-related behavioral change. Family
      members without diabetes provided reinforcements for dietary change for those
      with diabetes by preparing healthy food and monitoring intake, as well as by
      adopting dietary changes made by those with diabetes. Family and community
      members served as sources of observational learning about the potential impacts
      of diabetes and enhanced behavioral capability for dietary change among people
      with diabetes by providing dietary advice and strategies for making healthy
      choices. CONCLUSIONS: This study demonstrates the ways in which family and
      community members can influence dietary change in people with diabetes.
      Interventions targeting diabetes management should incorporate families and
      communities as sources of information, learning, and support.

PMID- 24685844
TI  - Advertisements in medical journals.

PMID- 24685842
TI  - Partnering With Families to Refine and Expand a Diabetes Intervention for Mexican
      Americans.
AB  - PURPOSE: The purpose of this study was to refine and expand a culturally tailored
      individual-level diabetes self-management intervention to a family-level
      intervention. METHODS: Using community-based participatory research principles,
      Mexican American adults (n = 12) with type 2 diabetes mellitus (T2DM) and family
      members (n = 12) in the United States-Mexico border region participated in 6
      focus group interviews, conducted by bilingual, bicultural facilitators.
      Facilitators and barriers to T2DM management were identified. Transcripts were
      analyzed using qualitative content analysis. RESULTS: Through an iterative
      analysis process, 5 categories represented participants with T2DM: (1) strategies
      my family can use to support our managing T2DM, (2) be sensitive to my
      challenges, (3) stop telling me what to eat or do, (4) how can we peacefully
      coexist, and (5) I feel supported. Categories identified by family members were
      (1) changing behaviors together, (2) sharing not controlling, (3) supporting
      positive behaviors, and (4) your behaviors frustrate me. CONCLUSIONS: The family
      was reinforced as a major influence for successful T2DM management. Family
      support requires that families value and develop knowledge and skills for T2DM
      management. This family intervention builds on family assets and relationships,
      shifting from traditional externally motivated individual models to create a
      shared commitment to manage T2DM among Mexican American adults.

PMID- 24685847
TI  - A randomized placebo-controlled double-blind pilot study of methotrexate in the
      treatment of H1 antihistamine-resistant chronic spontaneous urticaria.
AB  - BACKGROUND: Chronic urticaria not responsive to antihistamines is a difficult
      disease to manage. Methotrexate has been used in difficult chronic urticarias
      with some benefit. OBJECTIVE: To evaluate the efficacy of methotrexate in the
      treatment of chronic spontaneous urticaria poorly responsive to H1
      antihistaminics. METHODS: In a randomized double-blind trial at the Department of
      Dermatology and Venereology of a tertiary care centre, 29 patients with chronic
      spontaneous urticaria not responding well to H1 antihistaminics were recruited.
      Patients were randomly allocated to receive either a weekly dose of oral
      methotrexate 15 mg or placebo (calcium carbonate) for a total duration of 12
      weeks, after which treatment was stopped and patients were followed up for
      relapse of urticaria. Each group also received levocetrizine 5 mg once daily for
      symptom control. Primary outcome measured was a reduction by >2/3 rd of baseline
      urticaria scores after 12 week therapy. Secondary outcome was a reduction in
      antihistamine requirement after stopping therapy. RESULTS: Fourteen patients were
      randomized to the methotrexate group and fifteen patients to the placebo group.
      Out of 17 patients who completed therapy, the primary outcome was achieved by 3.5
      +/- 1.9 (out of 10) patients in the methotrexate group and by 3.67 +/- 1.03 (out
      of 7) patients in the placebo group (P > 0.05). Ten patients followed up, after
      stopping therapy, for a mean period of 3.5 +/- 2.4 months; 3 remained in
      remission and 7 had relapsed. One patient had uncontrollable nausea and vomiting
      after taking methotrexate and was withdrawn from the study. The placebo group did
      not experience any side effects. CONCLUSIONS: Methotrexate 15 mg weekly for 3
      months did not provide any additional benefit over H1 antihistamines in this
      study but an adequately powered study with longer follow up is required to assess
      its utility.

PMID- 24685845
TI  - Understanding itch: an update on mediators and mechanisms of pruritus.
AB  - Pruritus is the most common symptom secondary to skin diseases. Advances in the
      fields of neurobiology, immunology and physiology have made it possible for us to
      understand and unravel the deeper pathophysiological basis of pruritus. This
      review aims to update our current understanding of the mechanisms and mediators
      of pruritus. Special attention is paid to endogenous itch mediators particularly
      newly identified ones like endovanilloids, opioids, neurotrophins, cannabinoids,
      proteases and cytokines. Various theories explaining the peripheral encoding of
      itch are reviewed. Multiple neural pathways including the central itch pathways
      as well as supraspinal processing of itch and brain areas involved in pruritus
      are highlighted. Apart from peripheral itch mediators, spinal neural receptors
      are also involved in control of itch and should form part of the development of a
      novel antipruritic strategy. Further studies are required to fill the lacunae in
      our current understanding of the pathophysiology of pruritus. 

PMID- 24685852
TI  - Old-world leishmaniasis presenting as a nasal mass.
AB  - Mucosal leishmaniasis is a major problem in Latin America but has been rarely
      noticed in our region. Although there have been a few reports of mucosal
      involvement especially in the oral cavity from Southwest Iran, yet none have been
      presented from the Northeast where Leishmania tropica is the major concern. We
      report a patient with endonasal leishmaniasis due to L. tropica, an extremely
      rare entity in immunocompetent patients in our region. He presented with a mass
      in the left nasal vestibule causing a sense of obstruction on the same side,
      accompanied by occasional rhinorrhea and mild epistaxis. This case exemplifies
      the need for considering leishmaniasis as a differential diagnosis for nasal
      obstruction in this endemic area. 

PMID- 24685849
TI  - Validation of a computer based objective structured clinical examination in the
      assessment of undergraduate dermatology courses.
AB  - Many teaching centers have now adopted objective structured clinical examination
      (OSCE) as an assessment method for undergraduate dermatology courses. A
      modification of the standard OSCE in dermatology is computer based or electronic
      OSCE (eOSCE). We attempted to validate the use of a computer-based OSCE in
      dermatology in a group of fifth year medical students. The scores of the students
      in the computer-based OSCE showed a strong positive correlation with the scores
      on the clinical presentation (Pearson's co-efficient - 0.923, P value <0.000,
      significant at the 0.01 level) and a good correlation with overall scores of the
      student (Pearson's co-efficient - 0.728, P value <0.000, significant at the 0.01
      level), indicating that this is a reliable method for assessment in dermatology.
      Generally, the students' feedback regarding the methods was positive. 

PMID- 24685851
TI  - Tumor of follicular infundibulum: an unsuspected cause of macular
      hypopigmentation.
AB  - We present three cases of a rare eruptive variant of tumor of follicular
      infundibulum. Two patients presented with hypopigmented macules. The clinical
      differential diagnoses considered in these two cases were vitiligo, lichen
      sclerosus et atrophicus, and idiopathic guttate hypomelanosis. In the third case,
      the lesions were hypopigmented flat topped maculo-papules diagnosed clinically as
      verruca plana. In all three cases, the histopathological features of plate like
      growth of pale keratinocytes connected to the epidermis and peritumoral
      condensation of elastic fibers were diagnostic. Although no satisfactory
      treatment is available, the exclusion of other clinical differential diagnosis
      particularly vitiligo with its psychosocial implications underscores the
      importance of skin biopsy. 

PMID- 24685850
TI  - Extensive disseminated cysticercosis.
AB  - Cysticercosis, especially neurocysticercosis, is a major public health problem in
      India. We report an unusual case of disseminated cysticercosis with extensive
      infiltration of the skin, central nervous system, skeletal muscles, eye, lung,
      and heart. A patient with extensive cutaneous cysticercosis must be thoroughly
      investigated for widespread internal organ involvement. 

PMID- 24685846
TI  - Drug advertisements in two dermatology journals: a critical comparison of IJDVL
      and JAAD.
AB  - BACKGROUND: Though drug promotion regulations exist worldwide, low quality of
      journal drug advertising is a global issue. Medical journals are regarded as a
      leading source of information for new drugs. They may also modulate prescribing
      behavior of physicians without their knowledge. A comparative analysis of
      advertisements from different countries may provide insights regarding strengths
      and weaknesses of different regulating systems. AIMS: Prescription drug
      advertisements from the Indian Journal of Dermatology, Venereology, and Leprology
      (IJDVL) and Journal of American Academy of Dermatology (JAAD) were compared to
      check their compliance with criteria of World Health Organization (WHO) and
      International Federation of Pharmaceutical Manufacturers and Associations
      (IFPMA). METHODS: All the prescription drug advertisements of at least one page
      length appearing in all the issues of IJDVL and JAAD from January 2012 till
      December 2012 were included in this study. The contents of both advertisements
      were compared for compliance regarding different criteria of ethical codes for
      drug advertising of WHO and IFPMA. Statistical analysis was done using Fisher's
      exact test. RESULTS: Compared to IJDVL, more advertisements in JAAD complied with
      WHO and IFPMA codes. On the whole, advertisements in IJDVL had significantly less
      information regarding the approved usage, dosage, abbreviated prescribing
      information (API), summary of scientific information, safety information
      regarding the drug, and references to the scientific literature to support
      various claims. However, JAAD had more advertisements with multiple claims than
      IJDVL, and many advertisements interspersed between scientific articles while
      IJDVL had none. CONCLUSION: The complex issue of ethical drug advertising in
      dermatology journals requires constant review and discussion. Dermatologists
      should be cautious in assessing any advertisement or claim even if it seems
      evidence-based. The results from our study highlight the need for a global,
      proactive and effective regulatory system to ensure ethical medicinal drug
      advertising in medical journals.

PMID- 24685848
TI  - Extramammary Paget's disease: analysis of 17 Chinese cases.
AB  - BACKGROUND/OBJECTIVE: Extramammary Paget's Disease (EMPD) seems to be more common
      in Caucasians than Chinese. We report the clinical manifestations, management,
      and prognostic characteristics in 17 Chinese patients. METHODS: Medical records
      and biopsies of 17 patients who had been treated at a large university hospital
      in China between March 2005 and January 2012 were reviewed. RESULTS: Of the 17
      patients, 14 were men. They had lesions on the scrotum and the penis. Of the
      three women, two had vulvar and one had inguinal lesions. All patients underwent
      Mohs micrographic surgery (MMS). Three men had metastasis to the inguinal lymph
      nodes and underwent an extensive local excision with inguinal lymphadenectomy.
      Eight patients who had positive excision margins received additional radiation
      therapy. The mean follow-up duration was 54 months (4-85 months). One patient had
      two recurrences. Three had metastasis to the inguinal lymph node. One had
      metastasis to the bone and concomitant prostate cancer. Two patients died of the
      disease. CONCLUSION: A striking difference in presentation of EMPD in Chinese
      compared with Caucasians is the male predominance and location on the penis and
      scrotum. Mohs micrographic surgery followed by radiotherapy is an effective
      treatment. Long-term follow-up suggests that the disease has a good prognosis
      when it does not metastasise.

PMID- 24685853
TI  - Mucosal carotenoderma.

PMID- 24685856
TI  - Polycystic ovarian syndrome: a review.

PMID- 24685855
TI  - Polycystic ovarian disease: still an enigma!

PMID- 24685854
TI  - Flagellate dermatoses.

PMID- 24685859
TI  - Occupational contact dermatitis among construction workers: results of a pilot
      study.

PMID- 24685860
TI  - Syphilis among sexually transmitted infections clinic attendees in a tertiary
      care institution: a retrospective data analysis.

PMID- 24685857
TI  - Delleman syndrome or Haberland syndrome?

PMID- 24685863
TI  - Dermatomyositis and nasopharyngeal carcinoma in an Indian patient.

PMID- 24685861
TI  - Piebaldism with non-intertriginous freckles: what does it mean?

PMID- 24685858
TI  - Multibacillary leprosy: follow up observations on 19 patients treated with 12
      monthly doses of rifampicin, ofloxacin and minocycline therapy in Agra.

PMID- 24685862
TI  - Scrub typhus in a child: looking behind the ear and beyond.

PMID- 24685864
TI  - Epithelioid sarcoma of the extremities.

PMID- 24685865
TI  - Periocular granuloma annulare in a child.

PMID- 24685868
TI  - Treatment of multifocal epithelial hyperplasia with imiquimod.

PMID- 24685870
TI  - Disseminated molluscum contagiosum in a patient on methotrexate therapy for
      psoriasis.

PMID- 24685869
TI  - Central retinal artery occlusion and cerebral inrfaction following forehead
      injection with a corticosteroid suspension for vitiligo.

PMID- 24685871
TI  - Lindane toxicity following accidental oral ingestion.

PMID- 24685867
TI  - Mondor's disease.

PMID- 24685866
TI  - Distinctive manifestations of cutaneous intraneural perineurioma of fingers,
      compared with typical intraneural perineurioma.

PMID- 24685873
TI  - Adult variant of self-healing papular mucinosis in a patient treated with
      interferon alpha2a.

PMID- 24685872
TI  - Interstitial granulomatous drug reaction due to febuxostat.

PMID- 24685874
TI  - Severe eosinophilia during anti-tumor necrosis factor-alpha therapy for psoriatic
      arthritis.

PMID- 24685875
TI  - Unilateral Blaschkoid Darier's disease over the forehead.

PMID- 24685876
TI  - Multiple cutaneous nodules in a patient with rheumatoid arthritis.

PMID- 24685877
TI  - Clinico-mycological study of dermatophytes in a tertiary care centre in Northwest
      India.

PMID- 24685878
TI  - Retrospective analysis of fixed drug eruptions among patients attending a
      tertiary care center in Southern India.

PMID- 24685879
TI  - Effects of low-level light therapy on facial corticosteroid addiction dermatitis:
      a retrospective analysis of 170 Asian patients.

PMID- 24685880
TI  - Nevus lipomatosus cutaneus superficialis associated with nevus sebaceous of
      Jadassohn.

PMID- 24685881
TI  - Bullous pemphigoid after femur fracture surgery: a mere coincidence?

PMID- 24685882
TI  - Successful treatment of multiple facial basal cell carcinomas with imiquimod in a
      patient with chronic renal failure.

PMID- 24685883
TI  - Intraoperative Radiation Therapy in the Management of Gynecologic Malignancies.
AB  - OBJECTIVE: The aim of this study was to review the experience with intraoperative
      radiation therapy (IORT) in the treatment of gynecologic cancers at the
      Massachusetts General Hospital. METHODS: From January 1, 1994 to December 31,
      2011, 32 patients were treated with IORT at Massachusetts General Hospital.
      Hospital, pathology, and office medical records and radiation oncology records
      were reviewed. The Kaplan-Meier method was used to generate disease-free survival
      and overall survival (OS) data. RESULTS: In 27 patients (84.4), surgical
      resection margins were microscopically positive. In 5 patients (15.6%), margins
      were grossly positive. For patients with microscopic disease, 5-year disease-free
      survival was 40.9% (57 mo), compared with 9.1% (23 mo) for those with gross
      residual disease (P=0.001). Five-year OS was also statistically improved for
      patients with microscopic residual disease, when compared with OS among patients
      with gross residual disease, 77.3% (93 mo) and 54.5% (40 mo), respectively
      (P=0.001). The risk of distant metastases in patients with gross residual disease
      was 87%, compared with 28% in patients with microscopic disease (P=0.02).
      CONCLUSIONS: Volume of residual disease before IORT is an important prognostic
      indicator. Local recurrence and distant metastases were more common among
      patients with gross residual disease left in situ at time of IORT. Our
      institutional experience with IORT further supports the importance of complete
      surgical resection.

PMID- 24685884
TI  - Body Composition by Computed Tomography as a Predictor of Toxicity in Patients
      With Renal Cell Carcinoma Treated With Sunitinib.
AB  - BACKGROUND: Sunitinib is a standard first-line option for metastatic renal cell
      carcinoma (mRCC). Body composition is a prognostic factor in cancer patients and
      patients with loss of skeletal muscle mass and fat-free mass (FFM) are prone to
      dose-limiting toxicity (DLT) during targeted drug therapy. We investigated
      whether body composition by computed tomography predicted DLT from sunitinib in
      mRCC. METHODS: Patients with clear cell mRCC receiving sunitinib (50 mg) were
      included. Skeletal muscle cross-sectional area at L3 was measured by computed
      tomography. Sarcopenia was defined using published cutoffs. Toxicity was assessed
      after 4 cycles of the drug. RESULTS: Fifty-five patients (43 male), mean age 64
      years were included. Overall, 33% (N=18) of all patients were sarcopenic and of
      these 12.7% (N=7) were sarcopenic and overweight or obese. DLT occurred in <6
      months in 53% of patients (44% male vs. 83% female) and those who experienced DLT
      were older (68 vs. 60 y), had a lower skeletal muscle index (51.7 vs. 59.4 cm/m),
      a lower FFM (51.4 vs. 57.7 kg), and received a higher drug dose in mg/kg FFM (0.9
      vs. 0.8). Patients with the lowest compared with the highest measurements of
      skeletal muscle mass experienced more DLT, respectively, 92% versus 57% and
      experienced on average 5 toxicities versus 2. CONCLUSIONS: Sarcopenia is
      prevalent in patients with mRCC, is an occult condition in patients with
      normal/high body mass index, and is a significant predictor of DLT in patients
      receiving sunitinib. Our results highlight the potential use of baseline body
      composition to predict toxicity.

PMID- 24685885
TI  - Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC):
      the role of immune checkpoint inhibitors.
AB  - Immune checkpoint inhibition as a new treatment approach is undergoing extensive
      investigation in non-small cell lung cancer (NSCLC) and other malignancies.
      Unlike standard chemotherapy or targeted agents, which act directly on the tumor
      cells, immune checkpoint inhibitors work by restoring the immune system's
      capacity to eradicate tumors. Agents currently in active clinical development for
      lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte
      associated antigen 4 pathway, and multiple agents targeting the programmed death
      protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK
      3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for
      PD-1 (BMS-936559, MPDL3280A). Preliminary evidence shows activity for these
      agents in NSCLC as monotherapy or in combination with chemotherapy. This article
      reviews the immune checkpoint inhibitors and the available data to date on their
      use in lung cancer. Clinical implications for the use of these therapies in NSCLC
      are discussed as they relate to their novel mechanisms of action, response
      patterns, and safety profiles. 

PMID- 24685887
TI  - Partner's Perspective on Long-term Sexual Dysfunction After Prostate Cancer
      Treatment.
AB  - OBJECTIVE: Prostate cancer is the most common type of male cancer in the United
      States and the negative effect of prostate cancer treatment on sexual function
      has been well documented. The objective of this study was to examine the long
      term impact of sexual dysfunction on spouses or partners of prostate cancer
      survivors. METHODS: A total of 742 spouses of prostate cancer survivors was
      mailed surveys by the Michigan Public Health Institute, of which 379 were
      returned (51%). Nine surveys were excluded owing to study ineligibility. Spouses
      responding to the survey completed a combination of modified items from the
      Sexual Adjustment Questionnaire and researcher-developed items. RESULTS: Over 75%
      of spouses reported a decline in sex life quality after treatment. Communication
      about sexual issues between survivors and their health care providers was rated
      as good to excellent by 54.7% of partners, whereas 35.1% reported it as fair to
      poor. Approximately 60% of physicians initially recommended some form of sexual
      treatment. However, despite the persistence of sexual dysfunction, only 7% of the
      prostate cancer survivors were currently receiving treatment. Only 4.1% of health
      care providers referred the survivor to a sex therapist. CONCLUSIONS: Physicians
      need to understand the importance of the open, ongoing communication with
      prostate cancer survivors about sexual issues because sexual dysfunction seems to
      continue indefinitely after completion of treatment. Research on the
      effectiveness of behavioral interventions in restoring sexual health is
      critically needed for this population, especially as first-line sexual aids and
      medications are often not satisfactory solutions.

PMID- 24685886
TI  - Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus
      Cetuximab for Metastatic Pancreatic Cancer: An Eastern Cooperative Oncology Group
      Study.
AB  - OBJECTIVES: The primary objective was to determine the response rate in patients
      with metastatic pancreatic cancer treated in first line with irinotecan/docetaxel
      combination (Arm A) or with irinotecan/docetaxel/cetuximab combination (Arm B).
      Secondary endpoints were progression-free survival (PFS), overall survival (OS),
      toxicity, and the rate of thromboembolic events with prophylactic enoxaparin
      sodium. PATIENTS AND METHODS: Patients were eligible who had measurable,
      metastatic adenocarcinoma of the pancreas, and normal bilirubin. All patients
      received anticoagulation. Docetaxel (35 mg/m) and irinotecan (50 mg/m) were
      administered once a week for 4 weeks followed by 2 weeks rest (Arm A) alone or
      with the addition of cetuximab (Arm B). The primary endpoint was response rate.
      RESULTS: A total of 87 eligible patients were enrolled and treated. Grade 3/4
      toxicity was observed in 74% of patients in Arm A and 76% in Arm B. The principal
      grade 3/4 toxicity was diarrhea. Response rates were 4.5% in Arm A and 7% in Arm
      B. Median PFS and OS were 3.9 and 6.5 months in Arm A and 4.5 and 5.4 months in
      Arm B. CONCLUSIONS: Docetaxel/irinotecan combination is associated with
      considerable toxicity. Objective responses were infrequent and addition of
      cetuximab in an unselected population was not beneficial, but PFS and OS were
      comparable with those achieved with other regimens. Docetaxel/irinotecan therapy
      is active in metastatic pancreatic cancer.

PMID- 24685888
TI  - Revealing the role of SGK1 in the dynamics of medulloblastoma using a
      mathematical model.
AB  - Deregulation of signaling pathways and subsequent abnormal interactions of
      downstream genes very often results in carcinogenesis. In this paper, we propose
      a two-compartment model describing intricate dynamics of the target genes of the
      Wnt signaling pathway in medulloblastoma. The system of nine nonlinear ordinary
      differential equations accounts for the formation and dissociation of complexes
      as well as for the transcription, translation and transport between the cytoplasm
      and the nucleus. We focus on the interplay between MYC and SGK1 (serum and
      glucocorticoid-inducible kinase 1), which are the products of Wnt/beta-catenin
      signaling pathway, and GSK3beta (glycogen synthase kinase). Numerical simulations
      of the model solutions yield a better understanding of the process and indicate
      the importance of the SGK1 gene in the development of medulloblastoma, which has
      been confirmed in our recent experiments. The model is calibrated based on the
      gene expression microarray data for two types of medulloblastoma, characterized
      by monosomy and trisomy of chromosome 6q to highlight the difference between
      diagnoses. 

PMID- 24685889
TI  - System analysis of synonymous codon usage biases in archaeal virus genomes.
AB  - Recent studies of geothermally heated aquatic ecosystems have found widely
      divergent viruses with unusual morphotypes. Archaeal viruses isolated from these
      hot habitats usually have double-stranded DNA genomes, linear or circular, and
      can infect members of the Archaea domain. In this study, the synonymous codon
      usage bias (SCUB) and dinucleotide composition in the available complete archaeal
      virus genome sequences have been investigated. It was found that there is a
      significant variation in SCUB among different Archaeal virus species, which is
      mainly determined by the base composition. The outcome of correspondence analysis
      (COA) and Spearman's rank correlation analysis shows that codon usage of selected
      archaeal virus genes depends mainly on GC richness of genome, and the gene's
      function, albeit with smaller effects, also contributes to codon usage in this
      virus. Furthermore, this investigation reveals that aromaticity of each protein
      is also critical in affecting SCUB of these viral genes although it was less
      important than that of the mutational bias. Especially, mutational pressure may
      influence SCUB in SIRV1, SIRV2, ARV1, AFV1, and PhiCh1 viruses, whereas
      translational selection could play a leading role in HRPV1's SCUB. These
      conclusions not only can offer an insight into the codon usage biases of archaeal
      virus and subsequently the possible relationship between archaeal viruses and
      their host, but also may help in understanding the evolution of archaeal viruses
      and their gene classification, and more helpful to explore the origin of life and
      the evolution of biology. 

PMID- 24685891
TI  - Twist versus nonlinear stacking in short DNA molecules.
AB  - The denaturation of the double helix is a template for fundamental biological
      functions such as replication and transcription involving the formation of local
      fluctuational openings. The denaturation transition is studied for heterogeneous
      short sequences of DNA, i.e. ~100 base pairs, in the framework of a mesoscopic
      Hamiltonian model which accounts for the helicoidal geometry of the molecule. The
      theoretical background for the application of the path integral formalism to
      predictive analysis of the molecule thermodynamical properties is discussed. The
      base pair displacements with respect to the ground state are treated as paths
      whose temperature dependent amplitudes are governed by the thermal wavelength.
      The ensemble of base pairs paths is selected, at any temperature, consistently
      with both the model potential and the second law of thermodynamics. The partition
      function incorporates the effects of the base pair thermal fluctuations which
      become stronger close to the denaturation. The transition appears as a gradual
      phenomenon starting from the molecule segments rich in adenine-thymine base
      pairs. Computing the equilibrium thermodynamics, we focus on the interplay
      between twisting of the complementary strands around the molecule axis and
      nonlinear stacking potential: it is shown that the latter affects the melting
      profiles only if the rotational degrees of freedom are included in the
      Hamiltonian. The use of ladder Hamiltonian models for the DNA complementary
      strands in the pre-melting regime is questioned. 

PMID- 24685890
TI  - The dynamics of sperm detachment from epithelium in a coupled fluid-biochemical
      model of hyperactivated motility.
AB  - Hyperactivation in mammalian sperm is characterized by a high-amplitude,
      asymmetric flagellar waveform. A mechanical advantage of this hyperactivated
      waveform has been hypothesized to be the promotion of flagellar detachment from
      oviductal epithelium. In order to investigate the dynamics of a free-swimming
      sperm's binding and escaping from a surface, we present an integrative model that
      couples flagellar force generation and a viscous, incompressible fluid. The
      elastic flagellum is actuated by a preferred curvature model that depends upon an
      evolving calcium profile along its length. In addition, forces that arise due to
      elastic bonds that form and break between the flagellar head and the surface are
      accounted for. As in recent laboratory experiments, we find that a hyperactive
      waveform does result in frequent detaching and binding dynamics that is not
      observed for symmetric flagellar beats. Moreover, we demonstrate that flagellar
      behavior depends strongly on the assumptions of the bond model, suggesting the
      need for more experimental investigation of the biochemistry of epithelial
      bonding and the shedding of binding proteins on the sperm head. 

PMID- 24685892
TI  - Marshall bundle reentry: a novel type of macroreentrant atrial tachycardia.

PMID- 24685893
TI  - Bidirectional ventricular tachycardia associated with digoxin toxicity and with
      normal digoxin levels.

PMID- 24685894
TI  - The international journal of evidence-based Healthcare - quo vadis?

PMID- 24685895
TI  - Strategies to promote adherence to treatment by pulmonary tuberculosis patients:
      a systematic review.
AB  - OBJECTIVE: The objective of this study is to review and synthesise the best
      available research evidence that investigates the effectiveness of strategies to
      promote adherence to treatment by patients with newly diagnosed pulmonary
      tuberculosis (TB). METHODS: The search sought to find published and unpublished
      studies. The search covered articles published from 1990 to 2010 in English and
      Thai. The database search included Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), EMBASE, Cochrane Library, PubMed, Science Direct, Current
      Content Connect, Thai Nursing Research Database, Thai thesis database, Digital
      Library of Thailand Research Fund, Research of National Research Council of
      Thailand and Database of Office of Higher Education Commission. Studies were
      additionally identified from reference lists of all studies retrieved. Eligible
      studies were randomised controlled trials that explored different strategies to
      promote adherence to TB treatment of patients with newly diagnosed pulmonary TB
      and also included quasiexperimental studies. Two of the investigators
      independently assessed the studies and then extracted and summarised data from
      eligible studies. Extracted data were entered into Review Manager software and
      analysed. RESULTS: A total of 7972 newly diagnosed pulmonary TB patients
      participated in 10 randomised controlled trials and eight quasiexperimental
      studies. The studies reported on the effectiveness of a number of specific
      interventions to improve adherence to TB treatment among newly diagnosed
      pulmonary TB patients. These interventions included directly observed treatment
      (DOT) coupled with alternative patient supervision options, case management with
      DOT, short-course directly observed treatment, the intensive triad-model
      programme and an intervention package aimed at improved counselling and
      communication, decentralisation of treatment, patient choice of a DOT supporter
      and reinforcement of supervision activities. CONCLUSION: This review found
      evidence of beneficial effects from the DOT with regard to the medication
      adherence among TB patients in terms of cure rate and success rate. However, no
      beneficial effect was found from DOT intervention with increasing completion
      rate. In addition, the combined interventions to improve adherence to
      tuberculosis treatment included case management with directly observed treatment
      short-course program, the intensive triad-model programme and intervention
      package. These interventions should be implemented by healthcare providers and
      tailored to local contexts and circumstances, wherever appropriate.

PMID- 24685896
TI  - Evidence-based practice in the health and social services in China: developments,
      strategies, and challenges.
AB  - For the past decade, healthcare professionals and decision makers in China have
      made efforts to promote the development of evidence-based practice (EBP) in
      medicine and health services. In recent years, attention has been given to the
      use of EBP among other nonmedical fields, such as social work and education. The
      purpose of this article is to explore the current and the future development of
      EBP in health and social services in China. We first presented a brief account of
      EBP development in the Chinese context. Then, based on a literature search, we
      explored empirical foundations that may support the development and advancement
      of EBP in China. We also elaborated on some barriers that inhibit the development
      of EBP, and proposed strategies that are in place to overcome these barriers.
      This article concludes with a discussion of perceived challenges to the
      development of EBP in health and social services in China. 

PMID- 24685897
TI  - Managing peripheral intravenous devices in the adults' general surgical setting:
      a best practice implementation report.
AB  - AIM: The aim of this evidence-based practice (EBP) project was to promote
      adherence to the current best practice in monitoring and optimal replacement of
      peripheral intravenous device (PIVD). METHODS: This EBP project took place in a
      30-bed acute general surgical ward. Twenty in-patients with PIVD in situ for 4
      days or more were recruited. There were five stages in the project:
      identification of EBP topic, criteria, sample and setting; baseline;
      dissemination of baseline audit results and identification of best practice
      barriers; identification of barriers to EBP and implementation of strategies
      promoting EBP; and postimplementation audit. RESULTS: There were eight criteria
      in this project. The first audit showed moderate compliance in PIVD monitoring
      and optimal replacement. The project identified three barriers: lack of awareness
      of the current evidence-based guidelines, hospital policy not being aligned with
      current guidelines and no standard form of documentation. In order to overcome
      these barriers the following strategies were used: audit and feedback,
      interactive educational meetings, reminders and hospital policy change. The
      second audit showed minor improvements in each criterion. Compliance with
      documentation remained a challenge, possibly because of the lack of standardised
      documentation. DISCUSSION: Although the project did not render us the results we
      aimed for, it was successful because it highlighted the current EBP in PIVD
      management. The major challenges of the project were time and the lack of opinion
      leaders in our project team. We felt that more time was needed to adapt to the
      practice change and standardised documentation could not be developed in such a
      short time period. Further, the role of the opinion leader proved to be vital in
      this project. We felt that had we recruited more than one opinion leader, the
      results would have been different.

PMID- 24685898
TI  - Moving evidence to practice: reflections on a multisite academic-practice
      partnership.
AB  - This paper describes the challenges encountered by an academic team when working
      with clinical teams to translated knowledge for the purposes of quality
      improvement in multiple sites. The sites were four differing health care settings
      in a Northeastern US state: two acute care hospital sites (one rural, one urban),
      one visiting nurse service and one psychiatric specialty hospital were
      purposively chosen for the action research study. In conducting this study at
      these diverse sites the importance of developing relationships and trust,
      understanding the context and dealing with real world complexities were evident.
      We conclude with observations and recommendations on important elements for
      effective knowledge translation work. 

PMID- 24685899
TI  - Use of evidence-based practice in an aid organisation: a proposal to deal with
      the variety in terminology and methodology.
AB  - AIM: As part of its strategy Belgian Red Cross-Flanders underpins all its
      activities with evidence-based guidelines and systematic reviews. The aim of this
      publication is to describe in detail the methodology used to achieve this goal
      within an action-oriented organisation, in a timely and cost-effective way.
      METHODS: To demonstrate transparency in our methods, we wrote a methodological
      charter describing the way in which we develop evidence-based materials to
      support our activities. Criteria were drawn up for deciding on project priority
      and the choice of different types of projects (scoping reviews, systematic
      reviews and evidence-based guidelines). RESULTS: While searching for rigorous and
      realistically attainable methodological standards, we encountered a wide variety
      in terminology and methodology used in the field of evidence-based practice.
      Terminologies currently being used by different organisations and institutions
      include systematic reviews, systematic literature searches, evidence-based
      guidelines, rapid reviews, pragmatic systematic reviews, and rapid response
      service. It is not always clear what the definition and methodology is behind
      these terms and whether they are used consistently. We therefore describe the
      terminology and methodology used by Belgian Red Cross-Flanders; criteria for
      making methodological choices and details on the methodology we use are given.
      CONCLUSION: In our search for an appropriate methodology, taking into account
      time and resource constraints, we encountered an enormous variety of
      methodological approaches and terminology used for evidence-based materials. In
      light of this, we recommend that authors of evidence-based guidelines and reviews
      are transparent and clear about the methodology used. To be transparent about our
      approach, we developed a methodological charter. This charter may inspire other
      organisations that want to use evidence-based methodology to support their
      activities.

PMID- 24685900
TI  - Recommendations from international clinical guidelines for routine antenatal
      infection screening: does evidence matter?
AB  - AIM: Maternal infections in pregnancy may cause severe child morbidity. In this
      article, we aim to summarise recommendations from international evidence-based
      clinical guidelines for infection screening in pregnancy. METHODS: We conducted a
      systematic search for evidence-based guidelines in two databases (Guidelines
      International Network and National Guideline Clearinghouse) and a hand search on
      websites of international institutions and societies that develop evidence-based
      guidelines. We considered guidelines published from the 1 of January 2007 onwards
      and developed in Western, industrialised countries. The guidelines in our
      analysis had to be based on a systematic literature search in at least two
      databases and needed to provide recommendations explicitly linked to the
      evidence. We included five general antenatal clinical practice guidelines from
      Australia, UK and the United States and 20 disease-specific guidelines published
      by Canadian, German, UK and US guideline development groups. RESULTS: The
      comparison of evidence-based guidelines from nine different guideline development
      groups for 17 antenatal infection screenings showed variations in directions (pro
      screening or contra-screening) as well as in grades of recommendations.
      Uniformly, all-pro-universal or all-contra-universal screening recommendations
      were identified for 10 of 17 diseases. Contradictions were primarily observed for
      group B streptococcus, chlamydia trachomatis, genital herpes and gonorrhoea
      infection screening. Whereas certainty of recommendations was high for all-pro
      screening recommendations, it decreased in all-contra-screening recommendations
      and even displayed conflicting results for contradictory recommendations.
      CONCLUSION: The variety of grades of recommendations hamper across-guideline
      comparison. Nevertheless, the article highlights agreed screening areas based on
      the best available evidence as well as areas of still existing uncertainty. Local
      health policy decisions on whether to include or refrain from including screening
      measures in preventive care programmes can be facilitated by the comparison of
      recommendations from international evidence-based guidelines. Beyond the
      availability of evidence each country's health policy makers will have to make a
      judgement on the value of the test for a population-wide screening.

PMID- 24685901
TI  - The joint effects of room temperature ionic liquids and ordered media on
      fluorescence characteristics of estrogens in water and methanol.
AB  - This study investigated the steady-state and time-resolved fluorescence
      properties of 17alpha-ethinylestradiol (EE2) and 17beta-estradiol (E2) in the
      presence of ordered media (beta-cyclodextrins (beta-CD) and
      cetyltrimethylammonium bromide (CTAB)). In addition, we analyzed the effects of
      four room temperature ionic liquids (RTILs) on the fluorescence intensities (FIs)
      of EE2/beta-CD and E2/beta-CD inclusion complexes in methanol. Both beta-CD and
      CTAB enhanced the fluorescence of EE2 and E2. The FIs of EE2 and E2 with beta-CD
      or CTAB in methanol were greater than those in water, possibly resulting from
      decreased oxygen-quenching in H2O molecules. beta-CD and CTAB may form inclusion
      complexes with estrogen in both water and methanol. The inclusion ratio of the
      complex was 1:1 and the inclusion constant (K) values in water were greater than
      those in methanol. The fluorescence lifetimes were 2.50 and 4.13 ns for EE2 and
      2.58 and 4.03 ns for E2 in aqueous solution and methanol, respectively. The
      changing trend of fluorescence lifetimes for EE2 and E2 in beta-CD or CTAB was
      similar to the steady-state FIs. The four RTILs had a significant quenching
      effect on the FIs of EE2/beta-CD and E2/beta-CD, and the quenching process for
      EE2/beta-CD and E2/beta-CD by RTILs was demonstrated to be a dynamic quenching
      mechanism. Fluorescent data obtained from these complex systems provide a
      theoretical foundation for understanding the interaction mechanisms between
      ordered media and RTILs in the analysis of estrogens.

PMID- 24685902
TI  - Gambogic acid exhibits anti-psoriatic efficacy through inhibition of angiogenesis
      and inflammation.
AB  - BACKGROUND: Psoriasis is a chronic T cell-mediated inflammatory skin disease.
      Studies have shown that angiogenesis plays an important role in the pathogenesis
      of psoriasis. Studies have also indicated that Gambogic acid (GA) inhibits
      angiogenesis and may be a viable drug candidate in anti-angiogenesis therapies.
      OBJECTIVE: The aim of this study was to investigate the anti-psoriatic effect of
      GA and the possible mechanisms. METHODS: MTT test on HaCaT cells and
      immunofluorescence on HUVEC cells were processed. An O/W cream of GA was prepared
      and topically applied to the ears of K14-VEGF transgenic mice and psoriasis-like
      guinea-pigs, and the tail skin of Balb/C mice independently. Furthermore,
      hematoxylin-eosin staining of tissues from three models and immunohistochemistry
      staining of ear samples from K14-VEGF mice were performed. RESULTS: In vitro, GA
      inhibited proliferation of HaCaTs and TNF-alpha-induced activation of NF-kappaB
      in HUVECs. In vivo, animals treated with GA showed significant morphological and
      histological improvements. Immunohistochemical analysis of K14-VEGF transgenic
      mice revealed that hyperplastic and inflamed vessels were suppressed with GA
      treatment. The expression of adhesion molecules such as ICAM-1 and E-selectin was
      significantly decreased. GA inhibited angiogenesis and the expression of VEGFR2
      and p-VEGFR2. T lymphocyte infiltration and the expression of IL-17 and IL-22
      were also reduced by GA treatment. CONCLUSION: Our results suggest that GA has
      anti-psoriatic efficacy through inhibition of angiogenesis and inflammation.
      Therefore, GA is attractive and offers future potential for application in
      patients with psoriasis.

PMID- 24685903
TI  - Purinergic signaling via P2X7 receptor mediates IL-1beta production in Kupffer
      cells exposed to silica nanoparticle.
AB  - There is extensive evidence that nanoparticles (NPs) cause adverse effects in
      multiple organs, including liver, though the mechanisms involved remain to be
      fully established. Kupffer cells are macrophages resident in the liver, and play
      important roles in liver inflammation induced by various toxic agents, including
      lipopolysaccharide (LPS). Interleukin-1 (IL-1) family members IL-1alpha,beta are
      released from LPS-primed macrophages exposed to NPs, including silica NPs (SNPs),
      via activation of nucleotide-binding oligomerization domain-like receptor family
      pyrin domain-containing 3 inflammasomes. Here, we investigated the mechanism of
      production of IL-1beta via activation of inflammasomes in mouse Kupffer cell line
      KUP5, focusing on the role of purinergic signaling via P2X7 receptor. IL-1beta
      production by LPS-primed KUP5 cells exposed to SNPs was increased dose
      dependently, and was greatest in response to SNPs with a diameter of 30 nm
      (SNP30), as compared with 70-nm and 300-nm SNPs (SNP70 and SNP300). ATP release
      was also highest in cells exposed to SNP30. Treatment of LPS-primed KUP5 cells
      with ATP also induced a high level of IL-1beta production, similar to that
      induced by SNP30. IL-1beta production was significantly inhibited by apyrase (an
      ecto-nucleotidase) and A438079 (a P2X7 antagonist/ATP-release inhibitor).
      Production of reactive oxygen species (ROS) was confirmed in cells exposed to
      SNP30. In conclusion, ATP released from P2X7 receptor in response to stimulation
      of KUP5 cells with SNP30 induces ROS production via cell-membrane NADPH oxidase.
      The ROS causes activation of inflammasomes, leading to caspase-1-dependent
      processing of IL-1beta.

PMID- 24685904
TI  - Regulation of expression and activity of multidrug resistance proteins MRP2 and
      MDR1 by estrogenic compounds in Caco-2 cells. Role in prevention of xenobiotic
      induced cytotoxicity.
AB  - ABC transporters including MRP2, MDR1 and BCRP play a major role in tissue
      defense. Epidemiological and experimental studies suggest a cytoprotective role
      of estrogens in intestine, though the mechanism remains poorly understood. We
      evaluated whether pharmacologic concentrations of ethynylestradiol (EE, 0.05pM to
      5nM), or concentrations of genistein (GNT) associated with soy ingestion (0.1
      10MUM), affect the expression and activity of multidrug resistance proteins MRP2,
      MDR1 and BCRP using Caco-2 cells, an in vitro model of intestinal epithelium. We
      found that incubation with 5pM EE and 1MUM GNT for 48h increased expression and
      activity of both MRP2 and MDR1. Estrogens did not affect expression of BCRP
      protein at any concentration studied. Irrespective of the estrogen tested, up
      regulation of MDR1 and MRP2 protein was accompanied by increased levels of MDR1
      mRNA, whereas MRP2 mRNA remained unchanged. Cytotoxicity assays demonstrated
      association of MRP2 and MDR1 up-regulation with increased resistance to cell
      death induced by 1-chloro-2,4-dinitrobenzene, an MRP2 substrate precursor, and by
      paraquat, an MDR1 substrate. Experiments using an estrogen receptor (ER)
      antagonist implicate ER participation in MRP2 and MDR1 regulation. GNT but not EE
      increased the expression of ERbeta, the most abundant form in human intestine and
      in Caco-2 cells, which could lead in turn to increased sensitivity to estrogens.
      We conclude that specific concentrations of estrogens can confer resistance
      against cytotoxicity in Caco-2 cells, due in part to positive modulation of ABC
      transporters involved in extrusion of their toxic substrates. Although
      extrapolation of these results to the in vivo situation must be cautiously done,
      the data could explain tentatively the cytoprotective role of estrogens against
      chemical injury in intestine. 

PMID- 24685905
TI  - Situs ambiguous with left sided isomerism.

PMID- 24685906
TI  - Characterization and phylogeny of a novel methanotroph, Methyloglobulus morosus
      gen. nov., spec. nov.
AB  - A novel methanotrophic gammaproteobacterium, strain KoM1, was isolated from the
      profundal sediment of Lake Constance after initial enrichment in opposing
      gradients of methane and oxygen. Strain KoM1 grows on methane or methanol as its
      sole source of carbon and energy. It is a Gram-negative methanotroph, often
      expressing red pigmentation. Cells are short rods and occur sometimes in pairs or
      short chains. Strain KoM1 grows preferably at reduced oxygen concentrations
      (pO2=0.05-0.1bar). It can fix nitrogen, and grows at neutral pH and at
      temperatures between 4 and 30 degrees C. Phylogenetically, the closest relatives
      are Methylovulum miyakonense and Methylosoma difficile showing 91% 16S rRNA gene
      sequence identity. The only respiratory quinone is ubiquinone Q8; the main polar
      lipids are phosphatidyl ethanolamine and phosphatidyl glycerol. The major
      cellular fatty acids are summed feature 3 (presumably C16:1omega7c) and
      C16:1omega5c, and the G+C content of the DNA is 47.7mol%. Strain KoM1 is
      described as the type strain of a novel species within a new genus,
      Methyloglobulus morosus gen. nov., sp. nov. 

PMID- 24685907
TI  - Editorial Overview: Genome studies and molecular genetics: Genomic approaches to
      understanding evolution, development and the plant phenome.

PMID- 24685908
TI  - Drugs for plant chromosome and chromatin research.
AB  - Eukaryotic genomes are organized into chromosomes. Genetic information regularly
      becomes damaged and requires repair in order to ensure genome stability.
      Furthermore, expression of individual genetic elements on the chromosome(s) is
      controlled by several factors, including chromatin. Understanding the functions
      of chromatin may provide efficient tools for regulating gene expression. There
      has been great progress in understanding genome control using genetic mutations,
      but the use of mutants is sometimes not possible or may require additional
      interference with DNA or chromatin structure using specific treatments in order
      to obtain phenotypes. Therefore, chemical genetics has become an integral part of
      plant genome research. Here, we summarize information on the most commonly used
      drugs for chromatin and DNA damage repair studies, with the aim of simplifying
      the choice of drug and the estimation of possible side effects for current and
      future research.

PMID- 24685909
TI  - Improved performance of epidemiologic and genetic risk models for rheumatoid
      arthritis serologic phenotypes using family history.
AB  - OBJECTIVE: To develop and validate rheumatoid arthritis (RA) risk models based on
      family history, epidemiologic factors and known genetic risk factors. METHODS: We
      developed and validated models for RA based on known RA risk factors, among women
      in two cohorts: the Nurses' Health Study (NHS, 381 RA cases and 410 controls) and
      the Epidemiological Investigation of RA (EIRA, 1244 RA cases and 971 controls).
      Model discrimination was evaluated using the area under the receiver operating
      characteristic curve (AUC) in logistic regression models for the study population
      and for those with positive family history. The joint effect of family history
      with genetics, smoking and body mass index (BMI) was evaluated using logistic
      regression models to estimate ORs for RA. RESULTS: The complete model including
      family history, epidemiologic risk factors and genetics demonstrated AUCs of 0.74
      for seropositive RA in NHS and 0.77 for anti-citrullinated protein antibody
      (ACPA)-positive RA in EIRA. Among women with positive family history,
      discrimination was excellent for complete models for seropositive RA in NHS (AUC
      0.82) and ACPA-positive RA in EIRA (AUC 0.83). Positive family history, high
      genetic susceptibility, smoking and increased BMI had an OR of 21.73 for ACPA
      positive RA. CONCLUSIONS: We developed models for seropositive and seronegative
      RA phenotypes based on family history, epidemiological and genetic factors. Among
      those with positive family history, models using epidemiologic and genetic
      factors were highly discriminatory for seropositive and seronegative RA.
      Assessing epidemiological and genetic factors among those with positive family
      history may identify individuals suitable for RA prevention strategies.

PMID- 24685911
TI  - Pretreatment Epstein-Barr virus DNA load and cumulative cisplatin dose intensity
      affect long-term outcome of nasopharyngeal carcinoma treated with concurrent
      chemotherapy: experience of an institute in an endemic area.
AB  - BACKGROUND: We retrospectively compared the long-term efficacy of concurrent
      chemoradiotherapy (CCRT) regimens (docetaxel vs. cisplatin), total dose intensity
      of cisplatin (> 200 vs. <= 200 mg/m2) and pretreatment plasma levels of Epstein
      Barr virus (EBV) DNA for nasopharyngeal carcinoma (NPC), and investigated the
      prognostic factors. METHODS: We enrolled 214 patients diagnosed with NPC and
      treated with CCRT. 41 patients received weekly docetaxel and 173 weekly
      cisplatin. 62 received cumulative cisplatin of <= 200 mg/m2 and 111, > 200 mg/m2.
      Pretreatment levels of EBV DNA were available for 155 patients. RESULTS: Patients
      receiving concurrent weekly docetaxel and cisplatin had similar 5-year rates for
      overall survival (OS) (p = 0.306), progression-free survival (PFS) (p = 0.133),
      distant failure-free survival (DFS) (p = 0.110), and locoregional failure-free
      survival (LFS) (p = 0.452). Cumulative cisplatin of > 200 mg/m2 improved the 5
      year rates of PFS (p = 0.018) and DFS (p = 0.042) significantly in comparison
      with cumulative cisplatin of <= 200 mg/m2. EBV DNA levels of >= 1,500 copies/ml
      was closely associated with poor DFS (p = 0.011), PFS (p = 0.006), and OS (p =
      0.004). CONCLUSIONS : Weekly cisplatin was well tolerated in CCRT, during which
      cumulative cisplatin of > 200 mg/m2 improved PFS and DFS. The long-term efficacy
      of concurrent docetaxel was similar to that of concurrent cisplatin. The EBV DNA
      level was the most significant prognostic factor.

PMID- 24685910
TI  - Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy:
      results from the British Society for Rheumatology Biologics Register for
      Rheumatoid Arthritis.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk of
      certain solid cancers, in particular lung cancer, compared to the general
      population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may
      further enhance this risk. OBJECTIVES: To compare the risk of solid cancer in
      patients with RA treated with TNFi to that in patients treated with non-biologic
      (synthetic) disease modifying antirheumatic drugs (sDMARDs). METHODS: Patients
      with a physician diagnosis of RA enrolled in the British Society for Rheumatology
      Biologics Register, a national prospective cohort study established in 2001 to
      monitor the long-term safety of TNFi, were followed via record linkage with the
      national cancer registries until first solid cancer, death, for 5 years, or until
      2011. Rates of solid cancers in 11 767 patients without prior cancer who received
      TNFi were compared to those in 3249 patients without prior cancer treated with
      sDMARDs. RESULTS: 427 solid cancers were reported in 52 549 patient-years follow
      up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136
      cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI
      98 to 138) per 10 000 patient-years). After adjusting for differences in baseline
      characteristics there was no difference in risk of solid cancer for TNFi compared
      to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no
      difference in the relative risk of cancer for any of the individual TNFi drugs.
      CONCLUSIONS: The addition of TNFi to sDMARD does not alter the risk of cancer in
      RA patients selected for TNFi in the UK.

PMID- 24685912
TI  - Clinically staged cT2 adenocarcinomas of the gastroesophageal junction: accuracy
      of staging and therapeutic consequences.
AB  - BACKGROUND: Multimodality treatment options in locally advanced adenocarcinomas
      of the esophagogastric junction (AEGs) have been established in the last years.
      However, the therapeutic approach in patients with clinically staged cT2 tumors
      remains controversial. The most important determinant is the accuracy of clinical
      staging. We aimed to evaluate the association of clinical and histopathological
      staging in patients with cT2 tumors in respect of possible therapeutic
      consequences. PATIENTS AND METHODS: Between 2001 and 2011, 71 patients with AEG
      tumors were clinically staged as cT2 (cN0 = 48 (68%); cN+ = 23 (32%)) and
      underwent surgical resection. RESULTS: A primary tumor resection was performed in
      59 (83%) patients while 12 (17%) patients received neoadjuvant therapy. Primarily
      resected patients showed the following pT/pN categories: pT1: 13 (22%), pT2: 35
      (59%), pT3: 11 (19%), pN0: 23 (39%), whereas the clinical/histopathological pN
      category included 55% of the patients. Neoadjuvantly treated patients showed the
      following pT/pN categories: ypT0: 3 (25%), ypT1: 3 (25%), ypT2: 6 (50%), ypN0: 6
      (50%). The overall survival of primarily resected patients compared with patients
      undergoing neoadjuvant therapy was not significantly different. CONCLUSIONS: The
      accuracy of clinical staging in patients with cT2 tumors of the gastroesophageal
      junction is poor. As in primarily resected patients, over- and understaging
      balance each other; correct pretherapeutic staging occurs in just about 60% of
      the patients. Moreover, our study suggests that a radical surgical resection with
      adequate lymphadenectomy seems to be appropriate for cT2N0 and even in cT2N+
      tumors, since down-categorizing and prognosis are not improved for neoadjuvantly
      treated patients. However, the data have to be interpreted with caution because
      of the small patient numbers.

PMID- 24685913
TI  - THADA gene polymorphism and prostate cancer risk: a meta-analysis.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) rs1465618 in THADA at 2p21
      has been identified as being associated with prostate cancer (PCa) risk in
      Europeans; however, it is not clear whether the SNP is related to PCa risk in
      multiple populations. We investigated the association of rs1465618 in THADA with
      PCa in a Chinese population and carried out a meta-analysis in multiple
      populations, testing the relevance of this SNP for PCa risk. PATIENTS AND
      METHODS: We genotyped the SNP using high resolution melting (HRM) analysis and
      assessed its association with PCa risk in a case-control study of 289 PCa
      patients and 288 controls in a Chinese population. A meta-analysis was carried
      out with 36,313 PCa patients and 36,485 controls to evaluate the association of
      rs1465618 with PCa risk in multiple populations. RESULTS: rs1465618 in THADA was
      significantly associated with PCa risk (p = 0.026; odds ratio (OR) 1.327, 95%
      confidence interval (CI) 1.035-1.700). Furthermore, the rs1465618 variant
      genotype was associated with PCa aggressiveness (p = 0.044; OR = 2.053, 95% CI =
      1.015-6.602) in the Chinese population. The meta-analysis showed that rs1465618
      was significantly associated with PCa risk in multiple populations (p = 1.0*10(
      8); OR = 1.127, 95% CI = 1.085-1.171). CONCLUSION: Our results showed that
      rs1465618 in THADA may be a shared susceptibility variant for PCa in multiple
      populations. THADA gene polymorphisms may impact PCa susceptibility and
      progression.

PMID- 24685914
TI  - Investigation of using diffusion-weighted magnetic resonance imaging to evaluate
      the therapeutic effect of esophageal carcinoma treatment.
AB  - AIM: To explore the associations of diffusion-weighted magnetic resonance imaging
      (DWI) measurements with the therapeutic effect (TE) on and survival of esophageal
      carcinoma patients treated with chemoradiotherapy (CRT). METHODS: From March 2010
      to December 2011, 77 patients were prospectively enrolled into a cohort study.
      DWI was performed at the beginning and 1-3 months after CRT. The immediate post
      CRT TE was evaluated according to the Response Evaluation Criteria in Solid
      Tumors (RECIST). The associations between the disappearance status of
      hyperintense expression (HE) in DWI and the apparent diffusion coefficient (ADC)
      of DWI with the complete response (CR) as TE and survival were analyzed. RESULTS:
      3 patients were excluded due to the absence of HE in DWI. Analysis of the
      remaining 74 patients indicated that their ADC values were significantly improved
      from 1.64 +/- 0.48 to 2.65 +/- 0.58 mm2/s from pre-CRT to post-CRT (p = 0.000).
      Both univariate and multivariate Cox model analyses showed that high post-CRT ADC
      values and the disappearance status of HE associated significantly with the TE
      (CR rate) and survival. CONCLUSIONS: DWI examination could afford useful markers
      to predict the treatment response as well as the survival of patients with
      esophageal squamous cell carcinoma. The non-disappearance of HE in DWI and low
      ADC values after CRT were risk factors.

PMID- 24685915
TI  - MYC and MXI1 protein expression: potential prognostic significance in women with
      breast cancer in China.
AB  - OBJECTIVE: To investigate the expression levels and the clinical significance of
      MYC and MXI1 proteins in breast cancer. METHODS: The expression levels of MYC and
      MXI1 were detected by immunohistochemical assay in 166 cases of breast cancer;
      the relationships among MYC, MXI1 and the clinicopathological parameters were
      analyzed by chi2 test. Univariate analysis and Cox's proportional hazards model
      were used to evaluate the prognostic significance of the 2 proteins. RESULTS:
      27.71% of the tumor specimens showed high staining intensity for MYC (high
      expression group, HEG-MYC) and 22.89% showed high staining intensity for MXI1
      (HEG-MXI1); the expression of 2 proteins was negatively correlated (r = -0.177 p
      = 0.022). The Kaplan-Meier method for survival analysis showed that patients of
      the MYC-HEG demonstrated a significantly worse disease-specific survival than
      those of the MYC-low-expression group (LEG) (chi2 = 11.102, p = 0.001). However,
      patients of the MXI1-HEG had a significantly better disease-specific survival
      than those of the MXI1-LEG (chi2 = 7.858, p = 0.005). Both univariate analysis
      and Cox's proportional hazards model indicated that MYC and MXI1 could be
      independent prognostic molecular markers. CONCLUSION: MYC-HEG and MXI1-LEG levels
      are associated with poor prognosis in patients with breast cancer, suggesting
      that they may be useful molecular markers in breast cancer prognosis prediction.

PMID- 24685916
TI  - Metastatic hepatic epithelioid hemangio-endothelioma: long-term response to
      sunitinib malate.
AB  - BACKGROUND: Epithelioid hemangio-endothelioma (EHE) is a rare malignant tumor of
      vascular origin that electively metastasizes to lungs and liver. CASE REPORT: We
      report the case of a 51-year-old woman with metastatic and progressive EHE of the
      liver. She was successfully treated with daily administration of sunitinib
      malate, an oral multi-target tyrosine kinase inhibitor, which particularly
      targets vascular endothelial growth factor (VEGF) receptors. Stabilization has
      lasted 6 years. We discuss the rationale for using antiangiogenic treatment for
      EHE. CONCLUSION: This case adds to a growing body of evidence that suggests that
      antiangiogenic agents should be considered in patients who present with advanced
      EHE.

PMID- 24685917
TI  - Nab-paclitaxel for metastatic pancreatic cancer: clinical outcomes and potential
      mechanisms of action.
AB  - For almost 15 years there has been stagnation in the systemic treatment of
      patients with pancreatic ductal adenocarcinoma (PDAC). Recently, several
      developments seem to indicate clinically relevant improvements in the treatment
      of patients with metastatic disease. One of these developments is the
      introduction of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) into the
      firstline treatment of metastatic disease. In this review, underlying preclinical
      and clinical data are discussed, with a special focus on mechanisms of action,
      the potential interaction with albumin and calcium-binding matricellular
      glycoproteins, such as the secreted protein acidic and rich in cysteine (SPARC),
      as well as the clinical outcome associated with the use of nab-paclitaxel.

PMID- 24685918
TI  - Treatment algorithm for metastatic renal cell carcinoma--recommendations based on
      evidence and clinical practice.
AB  - Until a few years ago, the treatment options for metastatic renal cell cancer
      (mRCC) were very limited. The growing understanding of the molecular
      pathomechanisms underlying RCC allowed the development of new treatment
      approaches. Meanwhile, several approved target-oriented substances from different
      drug classes are available for mRCC. The mechanism of action of vascular
      endothelial growth factor (VEGF) and VEGF receptor or mTOR inhibition is well
      documented by phase III trials and reflected in the current guidelines. However,
      no predictive biomarkers have been identified in mRCC so far to demonstrate a
      benefit by a specific compound in an individual patient. Meanwhile, the
      sequential use of 'targeted therapies' in mRCC has been established as standard
      treatment. The optimal sequence of available agents is still unclear. A German
      RCC expert panel discussed and developed an algorithm for the choices of first-
      and second-line treatment in mRCC based on established clinical criteria.

PMID- 24685919
TI  - Fluoroscopic guide wire manipulation of malfunctioning peritoneal dialysis
      catheters initially placed by interventional radiologists.
AB  - PURPOSE: To assess the efficacy of fluoroscopic guide wire manipulation in
      patients with malfunctioning peritoneal dialysis (PD) catheters that were
      initially placed by interventional radiologists under fluoroscopic guidance.
      MATERIALS AND METHODS: From January 2002 to April 2012, 52 patients (mean age,
      52.8 y +/- 2.10s; range, 12-79 y) with malfunctioning PD catheters in whom
      fluoroscopic guide wire manipulation was performed were retrospectively reviewed.
      Technical success, clinical success, and complications were evaluated. Technical
      success was defined as fluoroscopically verified, successful catheter
      repositioning and adequate dialysate drainage after the procedure. Clinical
      success was defined as maintenance of PD catheter function for at least 30 days
      after the manipulation. RESULTS: During the study period, 72 manipulations (68
      initial manipulations and 4 remanipulations) for malfunctioning PD catheters were
      done. The technical success rate was 74% (50 of 68) for initial manipulations and
      75% (3 of 4) for remanipulations. The overall clinical success rate was 47% (32
      of 68) for initial manipulations and 0% (0 of 4) for remanipulations. The primary
      causes of catheter malfunction were extraluminal obstruction by omental wrapping
      or adhesions in 43 of 68 cases (63.2%) and catheter malposition in 25 of 68
      (36.8%) cases. There were no procedure-related major complications. CONCLUSIONS:
      Fluoroscopic guide wire manipulation in patients with malfunctioning PD catheters
      initially placed by interventional radiologists is a simple procedure, an
      effective way of prolonging PD catheter life, and a recommended procedure before
      invasive surgical procedures.

PMID- 24685920
TI  - Nuts may lower cancer risk.

PMID- 24685921
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685922
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685923
TI  - RE: Serum phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685924
TI  - Cancer risk: the fat tissue-BMI-obesity connection.

PMID- 24685926
TI  - RE: Serum phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685927
TI  - Response.

PMID- 24685928
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685929
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685930
TI  - More questions than answers surrounding e-cigarette debate.

PMID- 24685931
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685932
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685933
TI  - RE: Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial.

PMID- 24685934
TI  - Assessing mammography's benefits and harms.

PMID- 24685936
TI  - Enteral nutrition feeding alters antioxidant activity in unstimulated whole
      saliva composition of patients with neurological disorders.
AB  - Patients with neurological disorders have an increased risk of oral and systemic
      diseases due to compromised oral hygiene. If patients lose the ability to swallow
      and chew food as a result of their disorder, enteral nutrition is often utilized.
      However, this type of feeding may modify salivary antioxidant defenses, resulting
      in increased oxidative damage and the emergence of various diseases. The aim of
      this study was to evaluate the effects of enteral nutrition on biochemical
      parameters in the unstimulated whole saliva composition of patients with
      neurological disorders. For this, enzymatic (superoxide dismutase - SOD;
      glutathione peroxidase - GPx) and non-enzymatic (uric acid; ferric ion reducing
      antioxidant power - FRAP) antioxidant activity, as well as a marker for oxidative
      damage (thiobarbituric acid reactive substances - TBARS) were analyzed.
      Unstimulated whole saliva was collected from 12 patients with neurological
      disorders and tube-feeding (tube-fed group - TFG), 15 patients with neurological
      disorders and normal feeding via the mouth (non-tube-fed group - NTFG), and 12
      volunteers without neurological disorders (control group - CG). The daily oral
      hygiene procedures of TFG and NTFG patients were similar and dental care was
      provided monthly by the same institution's dentist. All patients exhibited
      adequate oral health conditions. The salivary levels of FRAP, uric acid, SOD,
      GPx, TBARS, and total protein were compared between studied groups. FRAP was
      increased (p<0.05) in the NTFG (4,651 +/- 192.5 mmol/mL) and the TFG (4,743 +/-
      116.7 mmol/mL) when compared with the CG (1,844 +/- 343.8 mmol/mL). GPx values
      were lower (p<0.05) in the NTGF (8.24 +/- 1.09 mmol/min/mg) and the TFG (8.37 +/-
      1.60 mmol/min/mg) than in the CG (15.30 +/- 2.61 mmol/min/mg). Uric acid in the
      TFG (1.57 +/- 0.23 mg/dL) was significantly lower than in the NTFG (2.34 +/-
      0.20mg/dL) and the CG (3.49 +/- 0.21 mg/dL). Protein was significantly lower in
      the TFG (5.35 +/- 0.27 g/dL) than in the NTFG (7.22 +/- 0.57 g/dL) and the CG
      (7.86 +/- 0.54 g/dL). There was no difference in the salivary flow rate and SOD
      between groups. Enteral nutrition in patients with neurological disorders was
      associated with lower oxidative damage, resulting in increased salivary
      antioxidant capacity. These results emphasize the importance of oral care for
      this population to prevent oral and systemic diseases.

PMID- 24685937
TI  - Acceptance and mindfulness-based stress management for support staff caring for
      individuals with intellectual disabilities.
AB  - Support staff working with individuals with intellectual disability (ID) and
      challenging behaviour experience high levels of work-related stress. Preliminary
      theoretical and experimental research has highlighted the potential suitability
      of acceptance and mindfulness approaches for addressing support staff stress.
      This study examines the effectiveness of an acceptance and mindfulness-based
      stress management workshop on the levels of psychological distress and well-being
      of support staff working with individuals with ID and challenging behaviour.
      Support staff (n=120) were randomly assigned to a workshop intervention condition
      (n=66) or to a waiting list control condition (n=54). Measurements were completed
      at three time points (pre-, post and 6 week follow-up) for: psychological
      distress, well-being, perceived work stressors, thought suppression, and
      emotional avoidance/psychological inflexibility. MAIN FINDINGS: The intervention
      led to significantly greater reductions in distress in the intervention group
      than in the control group. This was largely maintained at 6 week follow-up. This
      effect was more pronounced amongst a subsample that had shown higher levels of
      psychological distress at baseline. Thought suppression was found to reduce
      significantly in the intervention group between post intervention and follow-up,
      although no significant change was found in well-being or experiential
      avoidance/psychological inflexibility. Overall, results demonstrated support for
      the effectiveness of an acceptance and mindfulness-based intervention in reducing
      distress.

PMID- 24685938
TI  - Antioxidant intervention attenuates oxidative stress in children and teenagers
      with Down syndrome.
AB  - We previously demonstrated that systemic oxidative stress is present in Down
      syndrome (DS) patients. In the present study we investigated the antioxidant
      status in the peripheral blood of DS children and teenagers comparing such status
      before and after an antioxidant supplementation. Oxidative stress biomarkers were
      evaluated in the blood of DS patients (n=21) before and after a daily antioxidant
      intervention (vitamin E 400mg, C 500 mg) during 6 months. Healthy children (n=18)
      without DS were recruited as control group. The activity of superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR),
      glutathione S-transferase (GST), gamma-glutamyltransferase (GGT), glucose-6
      phosphate dehydrogenase (G6PD) and myeloperoxidase (MPO), as well as the contents
      of reduced glutathione (GSH), uric acid, vitamin E, thiobarbituric acid reactive
      substances (TBARS), and protein carbonyls (PC) were measured. Before the
      antioxidant therapy, DS patients presented decreased GST activity and GSH
      depletion; elevated SOD, CAT, GR, GGT and MPO activities; increased uric acid
      levels; while GPx and G6PD activities as well as vitamin E and TBARS levels were
      unaltered. After the antioxidant supplementation, SOD, CAT, GPx, GR, GGT and MPO
      activities were downregulated, while TBARS contents were strongly decreased in
      DS. Also, the antioxidant therapy did not change G6PD and GST activities as well
      as uric acid and PC levels, while it significantly increased GSH and vitamin E
      levels in DS patients. Our results clearly demonstrate that the antioxidant
      intervention with vitamins E and C attenuated the systemic oxidative damage
      present in DS patients.

PMID- 24685939
TI  - Sensorimotor function in preschool-aged children with expressive language
      disorder.
AB  - AIM: The aim of the study was to evaluate functional motor performance and haptic
      object recognition in 5-year-old children with mild expressive language disorder
      (ELD) in comparison with age- and gender-matched healthy children. METHODS: The
      subjects were classified by speech-language pathologist using The Reynell
      Developmental Language Scales III and Boehm Test of Basic Concepts: Preschool as
      children with mild ELD (n=29, incl. 23 boys and 6 girls) and children with
      typical language development as controls (n=29, incl. 23 boys and 6 girls). The
      children were examined for manual dexterity, ball skills, static and dynamic
      balance by Movement-ABC, haptic object recognition (HOR), hand-grip strength
      (HGS) and vertical jumping performance. RESULTS: Children with mild ELD
      demonstrated significantly higher scores (i.e., inferior performance) in all
      subtests of M-ABC (all p values <0.05), in haptic object recognition (p<0.01) and
      vertical jumping height (p<0.05) compared to controls. However, no statistically
      significant differences (p>0.05) emerged from HGS. Boys with mild ELD
      demonstrated higher results in impairment score (p<0.001), ball skills (p<0.01)
      and balance (p<0.01) of M-ABC, as well as in HOR (p<0.05). Girls with mild ELD
      showed higher impairment score (p<0.05) with lower percentile (p<0.05) in M-ABC,
      indicating inferior motor performance, and lower HGS for the non-dominant hand
      (p<0.05). Seven out of 29 (24.1%) children with mild ELD had definite or
      borderline motor difficulties, while only one child in control group (3.4%)
      demonstrated borderline motor difficulties. CONCLUSIONS: Children with mild
      expressive language disorder do not perform as well as controls in tests of
      functional motor skills, but their results in tests demanding maximal muscle
      force generation are in level with typically developing children. Boys and girls
      with mild ELD demonstrated higher impairment scores in M-ABC, indicating the need
      to follow their overall development more closely.

PMID- 24685940
TI  - Frequency domain analysis of ground reaction force in preadolescents with and
      without Down syndrome.
AB  - Children with Down syndrome (DS) display less stable and coordinated gait
      patterns in the time domain than their healthy peers. However, little is known
      about whether this group difference exists in the frequency domain. The purpose
      of this study was to investigate differences in vertical ground reaction force
      (GRF) in the frequency domain between preadolescents with and without DS. Twenty
      children at 7-10 years of age with and without DS participated in this study.
      Participants walked on an instrumented treadmill at two speeds with and without
      external ankle load. Vertical GRF was collected and the data was processed
      through a Fourier transform. Frequency content variables included fundamental
      frequency, power of the first five harmonics, and the frequency and number of
      harmonics at 95%, 99% and 99.5% of total power. Preadolescents with DS had a
      similar fundamental frequency as their healthy peers even though the DS group
      walked at slower speeds. The DS group displayed a different power spectrum of the
      first five harmonics and had the lower frequency and number of harmonics at 99%
      and 99.5% of total power. However, walking at a faster speed with external ankle
      load helped the DS group produce a power spectrum more similar to healthy
      children. Frequency content of vertical GRF provides additional assessment
      parameters in functional gait evaluation of children with DS. Treadmill
      intervention at a faster speed and with external ankle load appears to be
      clinically promising and needs further investigation. 

PMID- 24685941
TI  - Balance in children with attention deficit hyperactivity disorder-combined type.
AB  - The balance ability in children with attention deficit hyperactivity disorder
      combined type (ADHD-C) has not been fully examined, particularly dynamic sitting
      balance. Moreover, the findings of some published studies are contradictory. We
      examined the static and dynamic sitting balance ability in 20 children with ADHD
      C (mean age: 9 years 3 months; 18 boys, 2 girls) and 20 age-, sex-, height-,
      weight-, and IQ-matched healthy and typically developing controls (mean age: 9
      years 2 months; 18 boys, 2 girls). The balance subtests of the Movement
      Assessment Battery for Children (MABC) and the Bruininks-Oseretsky Test of Motor
      Proficiency (BOTMP) were used to compare the two groups, and a mechanical
      horseback riding test was recorded using a motion-capture system. Compared with
      the controls, children with ADHD-C had less-consistent patterns of movement, more
      deviation of movement area, and less-effective balance strategies during
      mechanical horseback riding. In addition, their performance on the balance
      subtests of the MABC and BOTMP were not as well as those of the controls. Our
      findings suggest that balance ability skill levels in children with ADHD-C were
      generally not as high as those of the controls in various aspects, including
      static and dynamic balance.

PMID- 24685942
TI  - Capnography in patients with severe neurological impairment.
AB  - Respiratory disease is a common reason for hospitalization and mortality in
      persons with severe intellectual and developmental disability. Capnography is the
      measurement and numerical display of end-tidal carbon dioxide (EtCO2). This was a
      prospective, case controlled, cross sectional study to assess differences of
      baseline EtCO2 values between neurologically impaired patients and healthy
      individuals. 86 neurologically impaired patients were evaluated in the study
      group. Their mean age +/- SD was 25.65 +/- 10.48 years with 41% males. 53 healthy
      children and young adults were evaluated in the control group. Their mean age +/-
      SD was 21.95 +/- 10.38 years with 54.7% males. Patients with severe neurological
      impairment had higher baseline EtCO2 values than healthy individuals.
      Kyphoscoliosis and the use of antipsychotic drugs were the major factors to
      increase EtCO2 levels. Knowing the patient's baseline EtCO2 value, as well as
      baseline oximetry, could guide treatment decisions, when assessing the patient's
      oxygenation and ventilation during acute respiratory illness, and can potentially
      prevent unnecessary laboratory and imaging investigations as well as over
      treatment. Future research can shed light on the utility of capnometry and
      clinical implications of higher baseline EtCO2 values among neurologically
      impaired patients.

PMID- 24685943
TI  - People with multiple disabilities learn to engage in occupation and work
      activities with the support of technology-aided programs.
AB  - These two studies were aimed at assessing technology-aided programs to help
      persons with multiple disabilities engage in basic occupation or work activities.
      Specifically, Study I focused on teaching two participants (an adolescent and an
      adult) with low vision or total blindness, severe/profound intellectual
      disabilities, and minimal object interaction to engage in constructive object
      manipulation responses. The technology monitored their responses and followed
      them with brief stimulation periods automatically. Study II focused on teaching
      three adults with deafness, severe visual impairment, and profound intellectual
      disabilities to perform a complex activity, that is, to assemble a five-component
      water pipe. The technology regulated (a) light cues to guide the participants
      through the workstations containing single pipe components and the carton for
      completed pipes and (b) stimulation events. The results of both studies were
      positive. The participants of Study I showed consistent and independent
      engagement in object-manipulation responses. The participants of Study II showed
      consistent and independent pipe assembling performance. General implications of
      the two programs and the related technology packages for intervention with
      persons with multiple disabilities are discussed.

PMID- 24685944
TI  - Dialkyl phosphates in amniotic fluid as a biomarker of fetal exposure to
      organophosphates in Crete, Greece; association with fetal growth.
AB  - The aim of this study was to evaluate fetal exposure to organophosphate
      pesticides (OPs) by measuring their non-specific dialkyl-phosphate metabolites
      (DAPs) in amniotic fluid (AF), and to examine the potential association between
      prenatal exposure and fetal growth. AF samples were collected from 415 women
      during the second gestational trimester. The determined OPs metabolites were DMP,
      DMTP, DEP, DETP, and DEDTP. DAPs were extracted by liquid-solid extraction,
      derivatized and analyzed by gas chromatography-mass spectrometry. 97.8% of AF
      samples were positive for at least one DAP. DAPs levels did not differ between
      urban and rural areas. Macrosomic neonates have significantly higher sum levels
      of DMPs (p=0.043), which exerted a linear positive association with birth-weight
      centile (b=4.43, p=0.016). Conclusively, as DAPs are detectable in AF they may be
      used as a potential biomarker of fetal exposure to OPs. Sum levels of DMPs appear
      to be associated with birth weight independently of other covariates. 

PMID- 24685945
TI  - Principles of rational design of thermally targeted liposomes for local drug
      delivery.
AB  - Drug release from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes
      occurs close to the main transition temperature Tm=41 degrees C. The exact
      release temperature can be adjusted by additional lipids, which shift Tm. A major
      issue is drug leakage at 37 degrees C. We here describe a novel approach with
      improved drug retention yet rapid release. To obtain spherical, smooth liposomes
      we included: i) 2mol% cholesterol, to soften bilayers (Lemmich et al 1997), ii)
      lipids, which due to their spontaneous curvature stabilize the negative and
      positive curvatures of the inner and outer leaflets of unilamellar liposomes. In
      addition to differential scanning calorimetry (DSC) and fluorescence
      spectroscopy, the lipid mixtures were analyzed by a Langmuir balance for their
      elastic properties and lipid packing, aiming at high elasticity modulus CS(-1).
      Maxima in CS(-1) coincided with minima in the free energy of lateral mixing.
      These liposomes have reduced drug leakage, yet retain rapid release. FROM THE
      CLINICAL EDITOR: This paper reports the development of optimized DPPC liposomes
      for drug delivery, with reduced drug leakage but maintained rapid release.

PMID- 24685946
TI  - Exosome-mediated delivery of functionally active miRNA-155 inhibitor to
      macrophages.
AB  - Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play
      pivotal roles in both physiological intercellular crosstalk and disease
      pathogenesis. Here, we showed that B cell-derived exosomes can function as
      vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or
      macrophages, respectively. Stimulation of B cells significantly increased exosome
      production. Unlike in parental cells, baseline level of miRNA-155 was very low in
      exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic
      significantly increased miRNA-155 levels in primary mouse hepatocytes and the
      liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155
      inhibitor loaded exosomes resulted in statistically significant reduction in LPS
      induced TNFalpha production and partially prevented LPS-induced decrease in SOCS1
      mRNA levels. Furthermore, exosome-mediated miRNA-155 inhibitor delivery resulted
      in functionally more efficient inhibition and less cellular toxicity compared to
      conventional transfection methods. Similar approaches could be useful in
      modification of target biomolecules in vitro and in vivo. From the clinical
      editor: In this study, exosome-based delivery of miRNA-155 mimicker or inhibitor
      was found to have significant biological response in hepatocytes and macrophages.
      Exosome-based approaches may be useful in the modification of other target
      biomolecules.

PMID- 24685947
TI  - Suppressor of cytokine signaling 3 is a negative regulator for neointimal
      hyperplasia of vein graft stenosis.
AB  - Coronary artery bypass graft (CABG) surgery is one of the most effective
      treatments for coronary artery disease. However, neointimal hyperplasia and
      ultimate luminal occlusion that is caused by vascular smooth muscle cell (VSMC)
      migration, proliferation and inflammatory response impede the long-term
      prognosis. The SOCS3 protein is involved in modulating various autoimmune and
      inflammatory diseases. However, the role of SOCS3 in vein graft disease is still
      unclear. We found that the mRNA and protein expression levels of IL-1beta, IL-6,
      MCP-1, ICAM-1, TNF-alpha, STAT3, P-STAT3 and SOCS3 were significantly higher in
      the graft samples compared to normal veins. After transfecting the recombinant
      adenovirus carrying the rat SOCS3 gene into cultured rat VSMCs or grafting veins
      in rat, SOCS3 overexpression was found to significantly inhibit VSMC migration
      and proliferation in vitro and neointimal hyperplasia in vivo, respectively.
      Furthermore, SOCS3 overexpression inhibited VSMC migration and growth in vitro
      and alleviated VSMC inflammation in vitro by inhibiting STAT3 activation and
      phosphorylation. In conclusion, SOCS3 is a crucial physiological negative
      regulator for vein graft failure and provides a novel target for vein graft
      stenosis therapy after CABG.

PMID- 24685948
TI  - Withholding or termination of resuscitation in pediatric out-of-hospital
      traumatic cardiopulmonary arrest.
AB  - This multiorganizational literature review was undertaken to provide an evidence
      base for determining whether recommendations for out-of-hospital termination of
      resuscitation could be made for children who are victims of traumatic
      cardiopulmonary arrest. Although there is increasing acceptance of out-of
      hospital termination of resuscitation for adult traumatic cardiopulmonary arrest
      when there is no expectation of a good outcome, children are routinely excluded
      from state termination-of-resuscitation protocols. The decision to withhold
      resuscitative efforts in a child under specific circumstances (decapitation or
      dependent lividity, rigor mortis, etc) is reasonable. If there is any doubt as to
      the circumstances or timing of the traumatic cardiopulmonary arrest, under the
      current status of limiting termination of resuscitation in the field to persons
      older than 18 years in most states, resuscitation should be initiated and
      continued until arrival to the appropriate facility. If the patient has arrested,
      resuscitation has already exceeded 30 minutes, and the nearest facility is more
      than 30 minutes away, involvement of parents and family of these children in the
      decision-making process with assistance and guidance from medical professionals
      should be considered as part of an emphasis on family-centered care because the
      evidence suggests that either death or a poor outcome is inevitable. 

PMID- 24685949
TI  - Strength capacity and cardiometabolic risk clustering in adolescents.
AB  - OBJECTIVES: The purpose of this study was to determine the gender-specific
      independent association between muscular strength and cardiometabolic risk
      clustering in a large cohort (n = 1421) of children. METHODS: Principal component
      analysis was used to determine the pattern of risk clustering and to derive a
      continuous aggregate score (MetScore) from various cardiometabolic risk
      components: percent body fat (%BF), fasting glucose, blood pressure, plasma
      triglycerides levels, and HDL-cholesterol. Gender-stratified risk and MetScore
      were assessed by using general linear models and logistic regression for
      differences between strength tertiles, as well as independent associations with
      age, BMI, estimated cardiorespiratory fitness (CRF), physical activity, and
      muscular strength (normalized for body mass). RESULTS: In both boys (n = 670) and
      girls (n = 751), there were significant differences in cardiometabolic profiles
      across strength tertiles, such that stronger adolescents had lower overall risk.
      Age, BMI, cardiorespiratory fitness, physical activity participation, and
      strength were all individually correlated with multiple risk components, as well
      as the overall MetScore. However, in the adjusted model, only BMI (beta = 0.30),
      physical inactivity (beta = 0.30), and normalized strength capacity (beta = -1.5)
      emerged as significant (P < .05) predictors of MetScore. %BF was the strongest
      loading coefficient within the principal component analysis-derived MetScore
      outcome. CONCLUSIONS: Normalized strength is independently associated with lower
      cardiometabolic risk in boys and girls. Moreover, %BF was associated with all
      cardiometabolic risk factors and carried the strongest loading coefficient. These
      findings bolster the importance of early strength acquisition and healthy body
      composition in childhood.

PMID- 24685950
TI  - The epidemiology and clinical features of Kawasaki disease in Australia.
AB  - OBJECTIVES: The current Australian epidemiology of Kawasaki disease (KD) is
      poorly defined. Previous enhanced surveillance (1993-1995) estimated an incidence
      of 3.7/100,000 <5 years. METHODS: We identified all patients hospitalized in
      Western Australia (current population ~2.4 million) 1979 through 2009 with a
      discharge diagnosis of KD. We reviewed demographic, clinical, laboratory, and
      echocardiographic data from individual patient files and derived age-specific
      population estimates. KD diagnosis was made using standard criteria. RESULTS:
      There were 353 KD cases, with incomplete KD in 34 (9.6%). Male to female ratio
      was 1.7:1 and median age was 3.8 years (interquartile range 12-60 months). Fifty
      (18.1%) patients were Asian. Mean annual incidence increased from 2.82 per
      100,000 children aged <5 years (95% confidence interval, 1.93-3.99) in 1980 to
      1989, to 7.96 (6.48-9.67) in 1990 to 1999, to 9.34 (7.72-11.20) in 2000 to 2009.
      The highest incidence was 15.7 in 2005. A total of 293 children (83%) received
      intravenous immunoglobulin and 331 (95.4%) aspirin. Of 282 children who completed
      echocardiographic studies, 47 (16.7%) had coronary artery (CA) ectasia/dilatation
      and 19 (6.8%) had CA aneurysms; male gender was significantly associated with CA
      abnormalities. CONCLUSIONS: KD epidemiology in Western Australia mirrors that of
      other industrialized, predominantly European-Caucasian populations. The rising
      incidence likely reflects both improved ascertainment and a real increase in
      disease burden. The current Australian incidence is threefold higher than
      previously reported and similar to the United Kingdom. The CA outcomes, which
      include the pre-intravenous immunoglobulin era, are comparable to those reported
      elsewhere.

PMID- 24685951
TI  - Live vaccine use and safety in DiGeorge syndrome.
AB  - OBJECTIVE: Live vaccines are generally contraindicated in patients with DiGeorge
      syndrome (DGS), a congenital disorder characterized by cellular immune
      deficiency. Vaccine utilization and safety in this population are not well
      described. This study examined vaccination patterns and adverse events following
      live immunization (AEFLI) in these individuals. METHODS: A multicenter
      retrospective cohort study was conducted in subjects with DGS confirmed by
      fluorescence in situ hybridization assay (chromosome 22q11.2 microdeletion). Live
      vaccine-preventable illnesses, vaccination coverage and timeliness, and AEFLIs in
      the 56-day window after live vaccination were examined. Bivariate and
      multivariable analyses assessed the impact of demographics medical history,
      timing of diagnostic confirmation, and preceding immune function on vaccination
      patterns and AEFLIs. RESULTS: Of 194 subjects, 77% and 75% received measles-mumps
      rubella (MMR) and varicella vaccines, respectively; 58% completed recommended
      vaccinations by age 19 to 35 months. Adverse events occurred after 14% and 20% of
      MMR and varicella vaccine doses, respectively. Most events were minor, few were
      serious, and no deaths were reported in post-live vaccination windows. Although
      early diagnostic confirmation negatively affected live vaccination coverage and
      timeliness (P < .001), baseline CD4% did not differ between subjects who did or
      did not receive live vaccines by 12 to 18 months. Among varicella vaccine
      recipients, those with a subsequent adverse event had a lower preceding CD4%
      (24.8% +/- 7.3%) than those without (35.5% +/- 11.7%) (P < .05); no CD4%
      differences were observed with MMR vaccination. Fourteen unvaccinated subjects
      experienced live vaccine-preventable illnesses. CONCLUSIONS: Live vaccines were
      frequently given and generally well-tolerated among patients with DGS with mild
      to-moderate immunosuppression.

PMID- 24685953
TI  - Clinical phenotype of scabies by age.
AB  - OBJECTIVE: Scabies has a clinical presentation that seems to vary according to
      age. We conducted a prospective study with the goal of delineating the clinical
      presentation of the disease into 3 groups of age: infants, <2 years; children, 2
      to 15 years; and adults, >15 years. METHODS: This trial was a prospective,
      multicenter observational study in consecutive patients with a confirmed
      diagnosis of scabies who were seen in 13 French Departments of Dermatology and
      Pediatric Dermatology between April 2010 and April 2011. A standardized
      questionnaire was completed for each patient. To identify factors associated with
      patient age, comparisons between the 3 age groups were conducted by using
      univariate and multivariate multinomial logistic regression analyses. RESULTS: A
      total of 323 individuals were included; the gender ratio (female:male) was 1.2:1.
      In univariate analysis, infants were more likely to have facial involvement. In
      multivariate logistic regression, relapse was more frequent in children (odds
      ratio [OR]: 2.45 [95% confidence interval (CI):1.23-4.88]) and infants (OR: 3.26
      [95% CI: 1.38-7.71]). In addition, family members with itch (OR: 2.47 [95% CI:
      1.04-5.89]), plantar (OR: 20.57 [95% CI: 7.22-58.60]), and scalp (OR: 16.94 [95%
      CI: 3.70-77.51]) involvement were also found to be independently associated with
      the age group <2 years. CONCLUSIONS: There is a specific clinical presentation of
      scabies in infants and children. Taking into account these specificities may be
      helpful for the early diagnosis and the identification of cases to prevent the
      propagation of the disease.

PMID- 24685954
TI  - Office-based preventive dental program and statewide trends in dental caries.
AB  - OBJECTIVES: To evaluate the impact of a North Carolina Medicaid preventive
      dentistry program in primary care medical offices (Into the Mouths of Babes
      Program [IMBP]) on decayed, missing, and filled teeth (dmft) of kindergarten
      students statewide and in schools with a large proportion of students from low
      income families. METHODS: An ecologic study using panel data of 920,505
      kindergarten students with 11,694 school-year observations examined the effect of
      the IMBP on dmft scores from 1998 to 2009. Ordinary least squares regression with
      fixed effects determined the association between IMBP visits per child 0 to 4
      years of age per county and mean dmft scores per kindergarten student per school,
      controlling for school-level poverty and ethnicity, county-level Medicaid
      enrollment, and supply of dentists and physicians. RESULTS: Mean dmft per
      kindergarten student per school increased from 1.53 in 1998 to 1.84 in 2004, then
      decreased to 1.59 in 2009. The mean number of IMBP visits per child 0 to 4 years
      of age per county increased from 0.01 in 2000 to 0.22 in 2009. A 1-unit increase
      in IMBP visits per county was associated with a 0.248 (95% confidence interval, 
      0.40 to -0.10) decrease in dmft per kindergarten student per school. For schools
      with more students at high risk for dental disease, a 1-unit increase in IMBP
      visits was associated with a 0.320 (95% confidence interval, -0.55 to -0.09)
      decrease in dmft. CONCLUSIONS: IMBP reduced dental caries among targeted
      vulnerable children, which helped reduce oral health disparities among preschool
      aged children in North Carolina.

PMID- 24685957
TI  - Chimerism of buccal membrane cells in a monochorionic dizygotic twin.
AB  - No monochorionic dizygotic twins (MCDZTs) with cellular chimerism involving cells
      other than blood cells have been reported in the literature to date. Here we
      report a probable first case of MCDZTs with buccal cell chimerism. A 32-year-old
      woman conceived twins by in vitro fertilization by using 2 cryopreserved
      blastocysts that were transferred into her uterus. An ultrasound scan at 8 weeks'
      gestation showed signs indicative of monochorionic twins. A healthy boy and a
      healthy girl were born, showing no sexual ambiguity. Cytogenetic analyses and
      microsatellite studies demonstrated chimerism in blood cells of both twins.
      Notably, repeated fluorescence in situ hybridization and microsatellite studies
      revealed chimerism in buccal cells obtained from 1 of the twins. Although the
      mechanism through which buccal cell chimerism was generated remains to be
      elucidated, ectopic differentiation of chimeric hematopoietic cells that migrated
      to the buccal membrane or the cellular transfer between the 2 embryos at the
      early stage of development might be responsible for the phenomenon. This
      hypothesis raises an interesting issue regarding embryonic development and
      cellular differentiation into organs during fetal development. Given the
      possibility of cryptic chimerism in various organs including gonadal tissues in
      MCDZTs, close observation will be required to determine whether complications
      develop in the course of the patients' growth. 

PMID- 24685956
TI  - Impact of the FITKids physical activity intervention on adiposity in prepubertal
      children.
AB  - OBJECTIVE: To investigate the effect of a 9-month physical activity intervention
      on cardiorespiratory fitness and adiposity among prepubertal children. METHODS:
      Prepubertal children (8- to 9-year-olds, N = 220, 103 girls) were randomly
      assigned to a 9-month physical activity intervention or a control group. The
      intervention provided 70 minutes (5 days/week) of moderate to vigorous physical
      activity. Maximum oxygen consumption (Vo2max percentile) and dual-energy
      radiograph absorptiometry measured cardiorespiratory fitness and adiposity,
      respectively. Intention-to-treat analysis was performed to assess baseline and
      follow-up cardiorespiratory fitness, percentage fat mass (%FM), percentage
      central fat mass (%CFM), and estimated visceral adipose tissue (VAT) area.
      RESULTS: The intervention group increased in cardiorespiratory fitness (5.4th
      percentile; 95% confidence interval [CI], 1.8 to 8.9) and decreased in %FM (
      0.7%; 95% CI, -1.1 to -0.4) and %CFM (-1.3%; 95% CI, -1.9 to -0.7). Reductions in
      %FM were evident for both nonoverweight (-0.62%; 95% CI, -1.07 to -0.17) and
      overweight or obese (-0.86%; 95% CI,-1.46 to -0.25) intervention participants.
      Conversely, the control group displayed no change in cardiorespiratory fitness
      while exhibiting increases in %FM (0.4%; 95% CI, 0.1 to 0.7), %CFM (0.6; 95% CI,
      0.1 to 1.1), and VAT area (3.0 cm(2); 95% CI, 1.6 to 4.4). Nonoverweight control
      participants increased in %FM (0.52%; 95% CI, 0.13 to 0.91), and their overweight
      and obese counterparts increased in VAT (4.76 cm(2); 95% CI, 1.90 to 7.63).
      CONCLUSIONS: The physical activity intervention improved cardiorespiratory
      fitness, reduced %FM, and prevented accumulation of %CFM among prepubertal
      children with varying adiposity levels. These findings provide support for daily
      physical activity recommendations to prevent excess fat mass accumulation in
      childhood.

PMID- 24685955
TI  - Free thyroxine levels after very preterm birth and neurodevelopmental outcomes at
      age 7 years.
AB  - BACKGROUND AND OBJECTIVES: Preterm infants commonly have transient
      hypothyroxinemia of prematurity after birth, which has been associated with
      deficits in general intellectual functioning, memory, attention, and academic
      achievement. However, research has predominantly focused on thyroxine levels in
      the first 2 weeks of life and outcomes are limited to the preschool period. Our
      objective was to evaluate the relationships between free thyroxine (fT4) levels
      over the first 6 weeks after very preterm (VPT) birth with cognitive functioning
      and brain development at age 7 years. METHODS: A total of 83 infants born VPT
      (<30 weeks' gestation) had fT4 concentrations measured postnatally and 2- and 6
      week area under the curve (AUC) summary measures were calculated. Follow-up at
      age 7 years included a neuropsychological assessment and brain MRI. Univariable
      and multivariable regression modeling was used where AUC for fT4 was the main
      predictor of neurodevelopmental outcome at age 7 years. RESULTS: Multivariable
      modeling revealed that higher, not lower, postnatal fT4 levels (2-week AUC) were
      associated with poorer cognitive performances at age 7 years on tasks of verbal
      learning (P = .02), verbal memory (P = .03), and simple reaction time (P < .001).
      A similar pattern of results was found when the 6-week AUC was examined. No
      significant associations between postnatal fT4 levels and brain volumes at age 7
      years were identified. CONCLUSIONS: Results are contradictory to previous
      observations and suggest that after adjustment for confounders, higher postnatal
      fT4 levels in VPT infants, rather than lower levels, may be a marker of adverse
      neuropsychological development in childhood.

PMID- 24685958
TI  - Reducing hypothermia in preterm infants following delivery.
AB  - BACKGROUND: Moderate hypothermia (temperature <36 degrees C) at birth is common
      in premature infants and is associated with increased mortality and morbidity.
      METHODS: A multidisciplinary practice plan was implemented to determine in
      premature infants <35 weeks old whether a multifaceted approach would reduce the
      number of inborn infants with an admitting axillary temperature <36 degrees C by
      20% without increasing exposure to a temperature >37.5 degrees C. The plan
      included use of occlusive wrap a transwarmer mattress and cap for all infants and
      maintaining an operating room temperature between 21 degrees C and 23 degrees C.
      Data were obtained at baseline (n = 66), during phasing in (n = 102), and at full
      implementation (n = 193). RESULTS: Infant axillary temperature in the delivery
      room (DR) increased from 36.1 degrees C +/- 0.6 degrees C to 36.2 degrees C +/-
      0.6 degrees C to 36.6 degrees C +/- 0.6 degrees C (P < .001), and admitting
      temperature increased from 36.0 degrees C +/- 0.8 degrees C to 36.3 degrees C +/-
      0.6 degrees C to 36.7 degrees C +/- 0.5 degrees C at baseline, phasing in, and
      full implementation, respectively (P < .001). The number of infants with
      temperature <36 degrees C decreased from 55% to 6.2% at baseline versus full
      implementation (P < .001), and intubation at 24 hours decreased from 39% to 17.6%
      (P = .005). There was no increase in the number of infants with a temperature
      >37.5 degrees C over time. The use of occlusive wrap, mattress, and cap increased
      from 33% to 88% at baseline versus full implementation. Control charts showed
      significant improvement in DR ambient temperature at baseline versus full
      implementation. CONCLUSIONS: The practice plan was associated with a significant
      increase in DR and admitting axillary infant temperatures and a corresponding
      decrease in the number of infants with moderate hypothermia. There was an
      associated reduction in intubation at 24 hours. These positive findings reflect
      increased compliance with the practice plan.

PMID- 24685960
TI  - Chylothorax in infants and children.
AB  - Chylothorax, the accumulation of chyle in the pleural space, is a relatively rare
      cause of pleural effusion in children. It can cause significant respiratory
      morbidity, as well as lead to malnutrition and immunodeficiency. Thus, a
      chylothorax requires timely diagnosis and treatment. This review will first
      discuss the anatomy and physiology of the lymphatic system and discuss various
      causes that can lead to development of a chylothorax in infants and children.
      Then, methods of diagnosis and treatment will be reviewed. Finally, complications
      of chylothorax will be reviewed. 

PMID- 24685959
TI  - Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for
      diabetes in youth study.
AB  - OBJECTIVE: To estimate temporal changes in the prevalence of diabetic
      ketoacidosis (DKA) at diagnosis of type 1 or type 2 diabetes in youth and to
      explore factors associated with its occurrence. METHODS: Five centers identified
      incident cases of diabetes among youth aged 0 to 19 years starting in 2002. DKA
      presence was defined as a bicarbonate level <15 mmol/L and/or a pH <7.25 (venous)
      or <7.30 (arterial or capillary) or mention of DKA in the medical records. We
      assessed trends in the prevalence of DKA over 3 time periods (2002-2003, 2004
      2005, and 2008-2010). Logistic regression was used to determine factors
      associated with DKA. RESULTS: In youth with type 1 diabetes (n = 5615), the
      prevalence of DKA was high and stable over time (30.2% in 2002-2003, 29.1% in
      2004-2005, and 31.1% in 2008-2010; P for trend = .42). Higher prevalence was
      associated with younger age at diagnosis (P < .0001), minority race/ethnicity (P
      = .019), income (P = .019), and lack of private health insurance (P = 008). Among
      youth with type 2 diabetes (n = 1425), DKA prevalence decreased from 11.7% in
      2002-2003 to 5.7% in 2008-2010 (P for trend = .005). Higher prevalence was
      associated with younger age at diagnosis (P = .001), minority race/ethnicity (P =
      .013), and male gender (P = .001). CONCLUSIONS: The frequency of DKA in youth
      with type 1 diabetes, although stable, remains high, indicating a persistent need
      for increased awareness of signs and symptoms of diabetes and better access to
      health care. In youth with type 2 diabetes, DKA at onset is less common and is
      decreasing over time.

PMID- 24685961
TI  - Percutaneous closure of patent foramen ovale with Atriasept II device in nickel
      allergic patients.
AB  - There are concerns about percutaneous closure of patent foramen ovale (PFO) using
      nitinol-alloys devices in patients with nickel hypersensitivity. We describe our
      experience with Atriasept II (Cardia Eagan, Minnesota, USA) used in four patients
      with known nickel allergy. No intraprocedural or in-hospital adverse events
      occurred. The follow-up was negative for allergic manifestations, without
      complications, as assessed by echocardiography. Because of the risk of adverse
      outcomes in nickel-allergic patients, devices with higher biocompatibility, low
      profile, and low nickel content should be preferred in cases of known
      hypersensitivity. Atriasept II, containing less metallic material, appears to be
      a safe option in allergic patients undergoing PFO closure. 

PMID- 24685962
TI  - Low pulse pressure as a poor-man's indicator of a low cardiac index in patients
      with severe cardiac dysfunction.
AB  - AIMS: A low pulse pressure (PP) may reflect poor cardiac output (CO), but has not
      been well characterized by invasive haemodynamic studies. METHODS: We
      investigated the relationship between PP and cardiac index (CI) in patients with
      cardiovascular disease including those with normal and impaired cardiac function.
      Cardiac catheterization data from 1897 patients was analysed. RESULTS: Mean age
      was 59 years; 57% were men, mean (SD) PP was 65 (25) mmHg and mean (SD) CI was
      2.9 (0.8) l/min/m. Correlation between CI and PP was absent if the CI was more
      than 3 l/min/m, with a weak correlation if CI was between 2 and 3 l/min/m (r =
      0.161; P < 0.001). For those with a CI of less than 2 l/min/m, the correlation
      was much stronger (r = 0.414; P < 0.001). In a multivariable regression analysis,
      a low PP predicted a low CI, at cardiac indices of less than 3 l/min/m. This was
      independent of potential confounders, including age, sex, presence of
      hypertension, presence of heart failure, presence of aortic stenosis, diabetes,
      renal function, heart rate, systemic vascular resistance, left ventricular end
      diastolic pressure and mean arterial pressure. CONCLUSION: In patients with a CI
      of less than 3 l/min/m, a low PP is a marker of a low CI. In patients with severe
      heart failure and a low CO, PP pressure might be useful as a 'poor-man's'
      surrogate of CO.

PMID- 24685964
TI  - An update on the benefits and risks of rosuvastatin therapy.
AB  - Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor
      (statin) that reduces low-density lipoprotein cholesterol levels to the greatest
      extent of all currently marketed statins. Prospective, randomized studies
      demonstrate the ability of rosuvastatin to reduce the risk of cardiovascular
      events and stabilize atherosclerosis. However, the efficacy of rosuvastatin in
      patient subpopulations (eg, patients with chronic kidney disease, women, ethnic
      subgroups) is not well described in the literature. To provide an updated,
      comprehensive review of the efficacy and safety of rosuvastatin, a literature
      search of PubMed was conducted using statins as a major topic, MESH topic, or a
      word in the title (including rosuvastatin, fluvastatin, atorvastatin,
      pitavastatin, lovastatin, pravastatin, and simvastatin). Publications selected
      for inclusion in this review were published from January 1, 2010 to December 31,
      2013, and provide new information pertaining to the efficacy and safety of
      rosuvastatin. 

PMID- 24685963
TI  - Impact of depression on circulating endothelial progenitor cells in patients with
      acute coronary syndromes: a pilot study.
AB  - AIMS: Depression has been identified as a risk factor for an adverse prognosis
      and reduced survival in patients with acute coronary syndrome (ACS). The number
      of endothelial progenitor cells (EPCs) is an independent predictor of clinical
      outcomes in patients with ACS. The aim of this study was to evaluate the impact
      of depression on EPC levels in patients with ACS. METHODS: Out of 74 ACS patients
      [23 non-ST-segment elevation myocardial infarction (NSTEMI), 48 STEMI], 36 had a
      diagnosis of major depressive episode (MDE) according to the Diagnostic and
      Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria at the time
      of the inclusion in the study. Control groups were as follows: 15 healthy
      individuals and 18 patients with current MDE without a history of cardiovascular
      diseases. EPCs were defined as CD34CD133KDR and evaluated by flow cytometry. All
      patients underwent standardized cardiological and psychopathological evaluations.
      Parametric and nonparametric statistical tests were performed wherever
      appropriate. RESULTS: ACS patients with MDE showed a significant decrease in
      circulating EPC number compared with ACS patients without MDE (P < 0.001). The
      ACS study population was then subdivided into STEMI and NSTEMI groups, and within
      each group patients with MDE again showed a significant decrease in circulating
      CD34CD133KDR EPCs compared with others (P <0.001). CONCLUSION: We showed that ACS
      patients with MDE have a reduced number of circulating CD34CD133KDR cells
      compared with ACS patients without MDE, suggesting that the presence of MDE
      reduces the response of bone marrow to acute ischemic events. Considering the
      reparative role of EPCs in ACS patients, we propose that patients with MDE might
      be protected less than patients without MDE.

PMID- 24685965
TI  - The hospitalist perspective on treatment of community-acquired bacterial
      pneumonia.
AB  - Community-acquired bacterial pneumonia (CABP) is an important health care concern
      in the United States and worldwide, and is associated with significant morbidity,
      mortality, and health care expenditure. Streptococcus pneumoniae is the most
      frequent causative pathogen of CABP. Other common pathogens include
      Staphylococcus aureus, Haemophilus influenzae, Enterobacteriaceae, Legionella
      pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. However, in
      clinical practice, the causative pathogen of CABP is most often not identified.
      Therefore, a common treatment approach for patients hospitalized with CABP is
      empiric antibiotic therapy with a beta-lactam in combination with a macrolide,
      respiratory fluoroquinolones, or tetracyclines. An increase in the incidence of
      S. pneumoniae that is resistant to frequently used antibiotics, including beta
      lactams, macrolides, and tetracyclines, provides a challenge for the physician
      when selecting empiric antimicrobial therapy. When patients with CABP do not
      respond to initial therapy, they must be adequately reevaluated with further
      diagnostic testing, change in antimicrobial regimen, and/or transfer of the
      patient to a higher level of care. The role of hospital medicine physicians is
      crucial in treating patients who are hospitalized with CABP. An important focus
      of hospitalists is to provide care improvement in a way that addresses both
      patient and hospital needs. It is essential that the hospitalist provides best
      possible patient care, including adherence to quality measures, optimizing the
      patient's hospital length of stay, and arranging adequate post-discharge care in
      an effort to prevent readmission and provide appropriate ongoing outpatient care.

PMID- 24685966
TI  - Clinical utility of implantable loop recorders.
AB  - Implantable loop recorders provide the highest sensitivity and accuracy of
      diagnosing cardiac arrhythmia that results in cardiac syncope. When
      bradyarrhythmia or tachyarrhythmia, including atrial fibrillation, is detected,
      appropriate secondary prevention therapy will be implemented, which will impact
      the long-term clinical outcome. An implantable loop recorder enables the
      clinician to record for a longer period of time, which increases the likelihood
      of detecting cardiac arrhythmia. Currently, this technology is being evaluated to
      diagnose a cardiac etiology of ischemic stroke and to optimize atrial
      fibrillation management that will predict the success of rhythm control and
      prevent thromboembolic events. This article reviews implantable loop recorder
      technology, and discusses the current indications, the outcomes of clinical
      studies and ongoing current studies, and future technological improvements. 

PMID- 24685967
TI  - Endothelial dysfunction in metabolic and vascular disorders.
AB  - Vascular endothelium has important regulatory functions in the cardiovascular
      system and a pivotal role in the maintenance of vascular health and metabolic
      homeostasis. It has long been recognized that endothelial dysfunction
      participates in the pathogenesis of atherosclerosis from early, preclinical
      lesions to advanced, thrombotic complications. In addition, endothelial
      dysfunction has been recently implicated in the development of insulin resistance
      and type 2 diabetes mellitus (T2DM). Considering that states of insulin
      resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose
      tolerance, and T2DM) represent the most prevalent metabolic disorders and risk
      factors for atherosclerosis, it is of considerable scientific and clinical
      interest that both metabolic and vascular disorders have endothelial dysfunction
      as a common background. Importantly, endothelial dysfunction has been associated
      with adverse outcomes in patients with established cardiovascular disease, and a
      growing body of evidence indicates that endothelial dysfunction also imparts
      adverse prognosis in states of insulin resistance. In this review, we discuss the
      association of insulin resistance and T2DM with endothelial dysfunction and
      vascular disease, with a focus on the underlying mechanisms and prognostic
      implications of the endothelial dysfunction in metabolic and vascular disorders.
      We also address current therapeutic strategies for the improvement of endothelial
      dysfunction. 

PMID- 24685968
TI  - The molecular biology and pathophysiology of vascular calcification.
AB  - Vascular calcification (VC), commonly encountered in renal failure, diabetes, and
      aging, is associated with a large increase in the risk for cardiovascular events
      and mortality. Calcification of the arterial media and of heart valves clearly
      plays a mediating role in this regard, whereas it is less clear how calcification
      of plaque influences atherogenesis and risk for plaque rupture. Vascular
      calcification is an active process in which vascular smooth muscle cells (VSMCs)
      adopt an osteoblastic phenotype and deposit hydroxyapatite crystals; apoptosis of
      VSMCs also promotes this deposition. Drivers of this phenotypic transition, which
      include elevated serum phosphate, advanced glycation end-products, bone
      morphogenetic proteins, inflammatory cytokines, and leptin, invariably induce
      oxidative stress in VSMCs, which appears to be a necessary and sufficient
      condition for induction of the runt-related transcription factor 2 gene (RUNX2)
      and the shift to osteoblastic behavior. Magnesium antagonizes the impact of
      phosphate on VSMC osteoblastic transition, both by a direct effect within VSMCs
      and by suppressing absorption of dietary phosphate. Antioxidants that suppress
      reduced nicotinamide adenine dinucleotide phosphate oxidase activity may have the
      potential to block the osteoblastic transition of VSMCs. Minimizing the
      absorption of dietary phosphate may also be helpful in this regard, particularly
      in renal failure, and it can be achieved with plant-based dietary choices,
      avoidance of phosphate additives, and administration of pharmaceutical phosphate
      binders, supplemental magnesium, and niacin. Good vitamin K status opposes VC by
      optimizing the gamma-carboxylation of matrix Gla protein, a physiological
      antagonist of VC. Adequate but not excessive vitamin D status also appears to
      discourage VC. Etidronate, a structural analogue of pyrophosphate, has shown
      potential for blocking VC. 

PMID- 24685969
TI  - Achieving serum urate goal: a comparative effectiveness study between allopurinol
      and febuxostat.
AB  - BACKGROUND: Febuxostat is recommended as 1 of 2 first-line urate-lowering
      therapies (ULT) for treating gout in the 2012 American College of Rheumatology
      Guidelines. Several efficacy trials have compared febuxostat with allopurinol
      treatment, but real-world comparative data are limited. METHODS: We compared
      effectiveness of the 2 agents in reaching serum urate (sUA) level goal (< 6
      mg/dL) within 6 months (main endpoint), factors impacting the likelihood of
      reaching goal, and outcomes in allopurinol patients who were switched to
      febuxostat therapy after failing to reach sUA level goal. Data from the General
      Electric Electronic Medical Record database on adult patients with newly
      diagnosed gout, who had started treatment with allopurinol or febuxostat in 2009
      or thereafter were analyzed. Descriptive statistics, bivariate analyses, and
      logistic regressions were used. RESULTS: Allopurinol (n = 17 199) and febuxostat
      (n = 1190) patients had a mean +/- standard deviation (SD) age of 63.7 (+/-
      13.37) years; most patients were men and white. Average daily medication doses
      (mg) in the first 6 months were 184.9 +/- 96.7 and 48.4 +/- 15.8 for allopurinol-
      and febuxostat-treated patients, respectively; 4.8% of allopurinol-treated
      patients switched to febuxostat, whereas 25.7% of febuxostat-treated patients
      switched to allopurinol. Febuxostat patients had lower estimated glomerular
      filtration rate levels, more diabetes mellitus, or tophi at baseline (P < 0.05)
      and 29.2% and 42.2% of patients in the allopurinol and febuxostat groups achieved
      goal sUA levels (P < 0.0001). Febuxostat was significantly more effective in
      patients reaching sUA goal (adjusted odds ratio, 1.73; 95% CI, 1.48-2.01). Older
      patients and women had greater likelihood of reaching sUA goal level; however,
      patients with higher Charlson Comorbidity Index scores, blacks, or those with
      estimated glomerular filtration rates between 15 to <= 60 mL/min had reduced
      likelihood of attaining goal (P < 0.05). Among allopurinol-treated patients who
      were switched to febuxostat after failing to reach goal, 244 (48.3%) reached goal
      on febuxostat (median = 62.5 days), with an average 39% sUA level reduction
      achieved within 6 months. Patients who did not reach goal had a 14.3% sUA level
      reduction. CONCLUSIONS: The real-life data support the effectiveness of
      febuxostat in managing patients with gout.

PMID- 24685970
TI  - Effects of parathyroid hormone-related peptide on the large conductance calcium
      activated potassium channel and calcium homeostasis in vascular smooth muscle
      cells.
AB  - AIM: To demonstrate the impact of the parathyroid hormone-related peptide (PTHrP)
      on the large conductance calcium-activated potassium (BKCa) channels in vascular
      smooth muscle cells (VSMC) and hyperpolarization of the cell membrane and its
      dependence on calcium. MATERIALS AND METHODS: VSMC were isolated from rat aorta
      and further subcultured. Four experiments were conducted in calcium-release
      measurements and each of them consisted of a control group, PTHrP, chemical
      substance, and PTHrP + chemical substance. Chemical substances used were:
      iberiotoxin, xestospongin C, xestospongin D, and thapsigargin, respectively. Fura
      2 imaging was used to determine changes in calcium release of VSMC. In membrane
      potential experiments, groups were designed similarly to the Fura-2 imaging
      experiments: iberiotoxin, BAPTA, and xestospongin D were added, in respective
      order. Changes in the membrane potential were examined using the fluorescence dye
      (DiBAC). RESULTS: Given in a dose between 0.01 and 1.0 MUmol/L, PTHrP caused a
      concentration-dependent decrease in fluorescence intensity, with a maximum effect
      at 0.5 MUmol/L. The decrease, therefore, demonstrated a PTHrP-induced
      hyperpolarization of the VSMC. The effect was blocked by use of iberiotoxin (100
      nmol/L), a highly selective inhibitor of BKCa. Furthermore, when the calcium
      chelator BAPTA (10 MUmol/L) was added, there was a significant reduction in PTHrP
      induced hyperpolarization. Use of PTHrP (0.5 MUmol/L) also decreased the
      fluorescence intensity of the indicator for intracellular calcium, Fura-2AM (a
      membrane-permeable derivative of Fura 2). This effect was re-blocked by use of
      iberiotoxin. Xestospongin C (3 MUmol/L) and xestospongin D (6 MUmol/L), both
      inhibitors of the inositol 1,4,5 trisphosphate-triggered calcium release,
      inhibited the effects of PTHrP. Additionally, thapsigargin (1 MUmol/L), a
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor, inhibited the effect of
      PTHrP. CONCLUSION: The results of our study show that PTHrP induces
      hyperpolarization and activates BKCa in VSMC. The activation of BKCa channels is
      calcium dependent; activation is linked to the inositol 1,4,5 trisphosphate
      triggered calcium release and is also dependent on the endo/sarcoplasmic
      reticulum calcium pump.

PMID- 24685971
TI  - Double-blind, placebo-controlled, crossover study of early-intervention with
      sumatriptan 85/naproxen sodium 500 in (truly) episodic migraine: what's neck pain
      got to do with it?
AB  - OBJECTIVE: Published studies of triptans in acute migraine have shown relatively
      disappointing 2-hour pain-free rates, ranging from 18% to 58%, with 2- to 24-hour
      sustained pain-free rates from 17% to 25%. A major flaw in the design of previous
      studies may have contributed to disappointing results: many subjects are not
      truly episodic in the nature of their headaches-they discount days with mild
      headache and ignore days with migraine-related neck pain. Believing that neck
      pain is integrally related to migraine, we sought to ascertain whether early
      treatment with sumatriptan 85/naproxen sodium 500 (sumatriptan/naproxen) in truly
      episodic migraineurs is more robust than results when neck pain has not been
      considered. METHODS: Successfully screened adult migraineurs who returned
      baseline diaries showing 2 to 7 migraine attacks monthly and < 15 headache and/or
      neck pain days/month received blister packs containing 3 sumatriptan/naproxen/1
      placebo for treatment of 4 migraines. Instructions were to treat within the first
      30 minutes of mild headache or neck discomfort-but only if the preceding day was
      completely free of both headache and neck pain. RESULTS: In our study, 63.9% of
      patient attacks treated with sumatriptan/naproxen achieved 2-hour pain freedom
      compared with 33.3% of those with placebo (P < 0.001). Sustained pain freedom (2
      24 hours) was achieved in 69.1% of sumatriptan/naproxen-treated attacks, compared
      with 23.3% with placebo (P < 0.01). More subjects using sumatriptan/naproxen
      achieved sustained pain freedom (than 2-hour pain freedom), due to 6 time points
      when the subject was sleeping/napping 2-hours post dose (5 sumatriptan/naproxen,
      1 placebo), yet attested to no discomfort between 2 and 24 hours post dose. Had
      the attacks been scored as pain-free at 2 hours, the 2-hour pain-free and
      sustained pain-free rates with sumatriptan/naproxen would have been identical at
      69.1% (vs 36.7% with placebo). With truly episodic migraineurs, pain freedom was
      significant as soon as 15 minutes following treatment with sumatriptan/naproxen
      (5.2% vs 0% with placebo; P < 0.01). CONCLUSION: Our study results support a
      fundamental re-evaluation of the role of neck pain in migraine.

PMID- 24685972
TI  - Antidepressants and sexual dysfunction: mechanisms and clinical implications.
AB  - INTRODUCTION: Depression is one of the more prevalent mental disorders in the
      United States, with estimates as high as 6.7% of Americans affected annually.
      Consequently, antidepressant use in the United States is also widespread. Both
      depression and its treatments are associated with sexual dysfunction (SD) in men
      and women, including orgasm and arousal problems, hypoactive sexual desire,
      premature ejaculation, erectile difficulties, and dyspareunia. Sexual dysfunction
      is frequently cited as a reason for nonadherence or discontinuation of treatment
      for depression. AIM: The objective of our review is to aid physicians, including
      primary care physicians, psychiatrists, and urologists/gynecologists, in the
      multidisciplinary approach to treating patients with SD and depression. METHODS:
      Our review focuses on articles published within the last 10 years on SD and
      depression in adults, with an emphasis on the relationship of treatments for
      depression on SD. SUMMARY: Different classes of antidepressants vary in their
      ability to cause sexual side effects. RESULTS: Treatment with selective serotonin
      reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors
      (SNRIs) is associated with SD. Use of other antidepressants, such as bupropion,
      mirtazapine, nefazodone, and vilazodone, have been associated with less SD
      compared with SSRIs; furthermore, some of the mentioned antidepressants have been
      used in the treatment of SD induced by SSRIs and SNRIs.

PMID- 24685973
TI  - Pharmacotherapy considerations in diabetes and obesity: setting patients up for
      success.
AB  - The causal relationship between obesity and type 2 diabetes mellitus has been
      acknowledged over the past few decades and is frequently expressed by the term
      diabesity. It is predicted that the number of people with diabetes mellitus (DM)
      and prediabetes will continue to rise, with obesity placing people at increased
      risk for diabetic complications and comorbidities. Therefore, an individualized,
      patient-centered care approach is needed to optimally treat and manage the obese
      patient with DM. With 11 classes of medications available to lower blood glucose
      levels, 2 new agents for weight loss, and various surgical procedures, the
      clinician and the patient have numerous options from which to choose. In an
      effort to promote optimal disease management, clinicians should work with their
      obese patients to select appropriate pharmacotherapy combinations that will
      enable the patients to successfully manage DM. The current clinical
      recommendations and guidelines emphasize the need to consider the weight effects
      of the various DM agents as monotherapy and in combination. Additionally, with
      the approval of 2 new weight loss medications, the clinician must be aware of the
      place of the medications in therapy and their appropriate use in combination with
      DM pharmacotherapy. 

PMID- 24685974
TI  - Combination phentermine/topiramate for obesity treatment in primary care: a
      review.
AB  - The treatment of obesity is often met with a myriad of challenges in the primary
      care setting. Nevertheless, a modest 5% weight loss is considered clinically
      significant and may be associated with health benefits. Phentermine/topiramate
      (Qsymia), available in the United States since September 2012, achieves
      clinically meaningful weight loss along with improvements in weight-related
      comorbidities. This combination drug therapy could be an additional tool for
      primary care providers in their quest for effective management of obesity.
      Special precautions and close monitoring are indicated when prescribing
      phentermine/topiramate for women of childbearing potential. Monitoring of heart
      rate and psychiatric and cognitive side effects is important. 

PMID- 24685975
TI  - Chest radiography in supporting the diagnosis of asthma in children with
      persistent cough.
AB  - OBJECTIVE: To establish whether chest radiographic findings suggestive of lower
      airway obstruction (LAO) disease support the diagnosis of asthma in pediatric
      patients with persistent cough in an outpatient setting. METHODS: 180 patient
      charts were reviewed. The patients were children aged 1 to 18 years referred over
      a 3-year period to a pediatric pulmonary subspecialty clinic for evaluation of
      cough lasting >= 4 weeks. Chest radiographic images obtained after the initial
      evaluation of 90 patients diagnosed with cough-variant asthma and 90 patients
      diagnosed with persistent cough from nonasthma origins were compared with
      radiologic findings of a control group consisting of patients with a positive
      tuberculin skin test and no respiratory symptoms. Increased peribronchial
      markings/peribronchial cuffing and hyperinflation were considered
      radiographically suggestive findings of LAO disease. RESULTS: Children diagnosed
      with cough-variant asthma at the initial evaluation had higher rates of chest
      radiographic findings suggestive of LAO disease (30.00%) than children with
      persistent cough from other causes (17.80%) or those with a positive tuberculin
      skin test and no respiratory symptoms (8.16%) (overall P value = 0.0063). They
      also had higher rates of spirometry abnormalities suggestive of an LAO defect.
      Children with chest radiographic findings suggestive of LAO disease were found to
      be younger than those with normal chest radiographic findings (5.0 +/- 2.7 years
      vs 8.6 +/- 4.7 years; P < 0.0001). CONCLUSION: This study suggests that chest
      radiographic findings indicative of an LAO in correlation with the clinical
      presentation can support the diagnostic suspicion of asthma, especially in
      younger children unable to perform spirometry.

PMID- 24685976
TI  - Psychosocial and pharmacological management of pain in pediatric sickle cell
      disease.
AB  - For children with sickle cell disease (SCD), pain is associated with significant
      current and future morbidity and mortality. Unfortunately, few evidence-based
      guidelines exist for the management of pain episodes in children with SCD. To
      inform empirically based treatment strategies for pain management in pediatric
      SCD, this review integrates and evaluates the extant literature on psychosocial
      and pharmacological approaches to the management of pain. Findings reveal a
      paucity of rigorous investigations of psychosocial and pharmacological pain
      management interventions in children with SCD. Psychosocial interventions
      included were primarily cognitive-behavioral in nature, whereas pharmacological
      approaches targeted non-opioid analgesics (ie, nonsteroidal anti-inflammatory
      drugs and corticosteroids) and opioid medications (ie, morphine and oxycodone).
      However, to date there is not a "gold standard" for pain management among
      children with SCD. Because psychosocial and physiological processes each play a
      role in the etiology and experience of pain, effective pain management requires
      multidimensional, comprehensive treatment approaches. Considering the significant
      impact of pain on functional outcomes and quality of life among children with
      SCD, additional clinical trials are warranted to ensure that interventions are
      safe and efficacious. 

PMID- 24685977
TI  - Management of chronic venous disease by general practitioners in Serbia: a cross
      sectional study.
AB  - BACKGROUND: Chronic venous disease (CVD) is one of the most prevalent medical
      conditions in the general population worldwide. OBJECTIVE: To evaluate the
      management of CVD provided by general practitioners (GPs). METHODS AND MATERIALS:
      The 2-center cross-sectional study comprised 2284 patients with CVD diagnosed and
      treated by GPs. Demographic and clinical data were obtained by physical
      examinations and standardized interviews. RESULTS: Patients were counseled about
      different types of therapy; lifestyle advice was recommended to 88.8%, venoactive
      drugs to 90.8%, compression therapy to 44.0% of patients, anticoagulants to
      16.7%, surgical treatment to 8.3%, and other types of therapy were recommended to
      7.8% of patients. The most common types of treatment were dual and triple
      therapies recommended to 39.5% and 33.1%, respectively. The number of therapies
      recommended to patients increased with CVD progression. Treatment was not
      recommended to < 1% of patients. Only 8.4% of patients were referred to a vein
      specialist. CONCLUSIONS: Although GPs had undergone special medical training
      about CVD before they were included in the study, some patients did not receive
      complete management of their condition. Continuous training of GPs and clinical
      guidelines for the management of CVD may help GPs to make adequate decisions.

PMID- 24685978
TI  - Collaborative care management effectively promotes self-management: patient
      evaluation of care management for depression in primary care.
AB  - BACKGROUND: Chronic disease management in the primary care setting increasingly
      involves self-management support from a nurse care manager. Prior research had
      shown patient acceptance and willingness to work with care managers. METHODS:
      This survey study evaluated patient-perceived satisfaction with care management
      and patient opinions on the effectiveness of care management in promoting self
      management. Qualitative and quantitative survey responses were collected from 125
      patients (79% female; average age 46; 94% Caucasian) enrolled in care management
      for depression. Qualitative responses were coded with methods of content analysis
      by 2 independent analysts. RESULTS: Patients were satisfied with depression care
      management. Patients felt that care management improved their treatment above and
      beyond other aspects of their depression treatment (mean score, 6.7 [SD, 2]; 10 =
      Very much), increased their understanding of depression self-management (mean
      score, 7.2 [SD, 2]; 10 = Very much), and increased the frequency of self
      management goal setting (mean score, 6.9 [SD, 3]; 10 = Very much). Predominant
      qualitative themes emphasized that patients value emotional, motivational, and
      relational aspects of the care manager relationship. Patients viewed care
      managers as caring and supportive, helpful in creating accountability for
      patients and knowledgeable in the area of depression care. Care managers empower
      patients to take on an active role in depression self-management. Some logistical
      challenges associated with a telephonic intervention are described. CONCLUSION:
      Care manager training should include communication and motivation strategies,
      specifically self-management education, as these strategies are valued by
      patients. Barriers to care management, such as scheduling telephone calls, should
      be addressed in future care management implementation and study.

PMID- 24685979
TI  - Etiology, evaluation, and management of nocturia in elderly men and women.
AB  - One of the most common problems affecting both elderly men and women is nocturia.
      Not only is nocturia a quality-of-life complaint, but the condition also is
      associated with increased morbidity and even mortality. Elderly people with
      nocturia are more at risk for hip fractures, resulting in an increased mortality.
      Nocturia can also be a harbinger of underlying disease states that can certainly
      affect a man or woman's quality of life in addition to the morbidity and
      mortality of those who suffer from this common medical problem. This article
      discusses the causes of nocturia, the evaluation, and the treatment options
      available for managing this common medical complaint that affects so many elderly
      patients. 

PMID- 24685980
TI  - Rational approaches, design strategies, structure activity relationship and
      mechanistic insights for anticancer hybrids.
AB  - A Hybrid drug which comprises the incorporation of two drug pharmacophores in one
      single molecule are basically designed to interact with multiple targets or to
      amplify its effect through action on another bio target as one single molecule or
      to counterbalance the known side effects associated with the other hybrid part(.)
      The present review article offers a detailed account of the design strategies
      employed for the synthesis of anticancer agents via molecular hybridization
      techniques. Over the years, the researchers have employed this technique to
      discover some promising chemical architectures displaying significant anticancer
      profiles. Molecular hybridization as a tool has been particularly utilized for
      targeting tubulin protein as exemplified through the number of research papers.
      The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin,
      phenstatins and vinca alkaloids have been utilized as one of the functionality of
      the hybrids and promising results have been obtained in most of the cases with
      some of the tubulin based hybrids exhibiting anticancer activity at nanomolar
      level. Linkage with steroids as biological carrier vector for anticancer drugs
      and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA
      interactive antitumor antibiotics derived from Streptomyces species in hybrid
      structure based drug design has also emerged as a potential strategy. Various
      heteroaryl based hybrids in particular isatin and coumarins have also been
      designed and reported to posses' remarkable inhibitory potential. Apart from
      presenting the design strategies, the article also highlights the structure
      activity relationship along with mechanistic insights revealed during the
      biological evaluation of the hybrids. 

PMID- 24685981
TI  - Apoptosis inducing lead compounds isolated from marine organisms of potential
      relevance in cancer treatment.
AB  - Apoptosis is a critical defense mechanism against the formation and progression
      of cancer and exhibits distinct morphological and biochemical traits. Targeting
      apoptotic pathways becomes an intriguing strategy for the development of
      chemotherapeutic agents particularly if the process is selective to cancer cells.
      Marine natural products have become important sources in the discovery of
      antitumour drugs, especially when recent technological and methodological
      advances have increased the scope of investigations of marine organisms. A high
      number of individual compounds from diverse organisms have induced apoptosis in
      several tumour cell lines via a number of mechanisms. Here, we review the effects
      of selected marine natural products and their synthetic derivatives on apoptosis
      signalling pathways in association with their pharmacological properties.
      Providing an outlook into the future, we also examine the factors that contribute
      to new discoveries and the difficulties associated with translating marine
      derived compounds into clinical trials. 

PMID- 24685982
TI  - Hypoxia-induced gene expression of aquaporin-4, cyclooxygenase-2 and hypoxia
      inducible factor 1alpha in rat cortical astroglia is inhibited by 17beta
      estradiol and progesterone.
AB  - 17beta-Estradiol (E2) and progesterone (P) are neuroprotective in acute brain
      injury by attenuating neuropathophysiological processes and regulating local
      glial function. Besides controlling brain-intrinsic immune responses, astrocytes
      are cellular targets for sex steroids in health and disease and typically resist
      to hypoxic damage. In this in vitro study, we aimed at uncovering astroglia
      specific reactions to sublethal hypoxic conditions and astroglia-specific effects
      of both sex steroid hormones on these parameters. Short-term hypoxia for 3 h
      increased reactive oxygen species production, but had no influence on cell
      viability of cerebral cortical rat astroglia. Astrocytes expressed classical
      estrogen receptors (ER), progesterone receptor (PR), and a set of nonclassical
      steroid hormone receptors. Hypoxia specifically induced ERalpha and PR isoform A
      gene expression. Oxygen deprivation increased gene expression of aquaporin-4
      (AQP4), hypoxia-inducible factor 1alpha (Hif1alpha), and cyclooxygenase-2 (COX2).
      The application of E2 and P selectively prevented this induction. Effects on
      protein levels of these genes appeared to be delayed. These data show that
      astrocytes change their receptivity for sex steroid hormones by switching steroid
      hormone receptor expression and that E2 and P modify or antagonize
      proinflammatory COX2 synthesis, edema-promoting AQP4 expression, and the
      Hif1alpha increase. In vivo studies have to address whether these cell responses
      contribute to steroid-mediated neuroprotection in stroke.

PMID- 24685983
TI  - Chemical exchange saturation transfer MRI using intermolecular double-quantum
      coherences with multiple refocusing pulses.
AB  - Chemical exchange saturation transfer (CEST) provides a new type of image
      contrast in MRI. Due to the intrinsically low CEST effect, new and improved
      experimental techniques are required to achieve reliable and quantitative CEST
      images. In the present work, we proposed a novel and more sensitive CEST
      acquisition approach, based on the intermolecular double-quantum coherence with a
      module of multiple refocusing pulses (iDQC-MRP). Experiments were performed on
      creatine and egg white phantoms using a Varian 7T animal MRI scanner. The iDQC
      MRP CEST technique showed a substantial enhancement in CEST and nuclear
      Overhauser enhancement (NOE) signal intensities, compared to the standard single
      quantum coherence approach. In addition, the iDQC-MRP approach increased the
      signal-to-noise ratio of acquired saturation images, compared to the conventional
      iDQC approach. The new iDQC-MRP CEST sequence provides a promising way for
      exploiting in vivo CEST and NOE imaging applications. 

PMID- 24685985
TI  - A functional fetal HSD11B2[CA]n microsatellite polymorphism is associated with
      maternal serum cortisol concentrations in pregnant women.
AB  - BACKGROUND/AIMS: Cortisol plays an important role during pregnancy. It controls
      maternal glucose metabolism and fetal development. Cortisol metabolism is
      partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and
      human placenta. The activity of the enzyme is partially controlled by functional
      polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this
      functional gene polymorphism on cortisol metabolism and potential effects on the
      newborn's is unknown so far. METHODS: In the current prospective birth cohort
      study in southern Asia, we analyzed the association of the HSD11B2[CA]n
      microsatellite polymorphisms in 187 mothers and their newborn's on maternal and
      newborn's serum cortisol concentrations. RESULTS: Using multivariable regression
      analyses considering known confounding (gestational age, newborn's gender, the
      labor uterine contraction states and the timing during the day of blood taking),
      we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first
      intron was related to maternal cortisol concentration (R2=0.26, B=96.27,
      p=0.007), whereas as the newborn's cortisol concentrations were independent of
      fetal and maternal HSD11B2[CA]n microsatellite polymorphism. CONCLUSIONS: Our
      study showed for the first time that the fetal HSD11B2[CA]n microsatellite
      polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is
      associated with maternal cortisol concentration. This indicates that fetal genes
      controlling cortisol metabolism may affect maternal cortisol concentration and
      hence physiology in healthy pregnant women.

PMID- 24685984
TI  - Long-term clinical evaluation of 211 two-unit cantilevered resin-bonded fixed
      partial dentures.
AB  - OBJECTIVES: This retrospective study aims to evaluate the long term clinical
      performance of two-unit cantilevered resin-bonded fixed partial dentures (RBFPDs)
      relating to their retention, success and survival rate. MATERIALS AND METHODS:
      Prostheses that were placed at least four years previously were clinically
      reviewed to evaluate retention, success and survival rate. Additional information
      was also collected, including patient's gender, age and satisfaction on their
      prosthesis, operator's experience, prosthesis service life, root canal therapy if
      performed, abutment mobility, bone support, the presence of shim-stock contacts
      on the abutment or pontic in intercuspal position, and the presence of proximal
      axial contacts adjacent to the prosthesis. The date of any debonding with
      subsequent treatment was also recorded. RESULTS: A total of 211 two-unit RBFPDs
      were placed in 153 patients, with a mean service life of 113.2+/-33.5 months.
      Twenty-eight prostheses debonded, resulting in a retention rate of 86.7 percent,
      and another five teeth were extracted with the prostheses, resulting in a success
      rate of 84.4 percent. 90.0 percent prostheses were functioning (survival rate) by
      means of rebonding at the time of review. The location of the replaced tooth had
      a significant effect on the retention of RBFPDs with posterior RBFPDs lower than
      anterior (p=0.020). Kaplan-Meier analysis revealed 5-, 10- and 15-year cumulative
      probability of surviving was 0.97, 0.91 and 0.84, respectively. CONCLUSIONS: 211
      two-unit RBFPDs were observed to have a success, retention and survival rate of
      84.4, 86.7 and 90.0 percent, respectively, with a mean service life of 9.4 years.
      CLINICAL SIGNIFICANCE: Based on the clinical results, two-unit RBFPD are shown to
      be a durable prosthesis over the long term with high patient satisfaction. The
      posterior prostheses, particularly in the lower arch appeared to have a higher
      failure rate, and improved design features should be considered.

PMID- 24685986
TI  - The protective effects of erythropoietin on rat glomerular podocytes in culture
      are modulated by extracellular matrix proteins.
AB  - BACKGROUND/AIMS: Podocytes are typically cultured on collagen I; however,
      collagen I is absent from healthy glomerular basement membranes. Erythropoietin
      (EPO) is thought to protect podocytes in vivo. Here, we studied how various types
      of extracellular matrix (ECM) proteins and EPO affect podocytes in culture.
      METHODS: Primary rat podocytes were replated on collagen I, collagen IV, whole
      ECM extract, laminin, or bare plastic. Cellular adhesion (8 hours after plating),
      proliferation (5 days, 10 % serum), and resistance to serum deprivation (3 days,
      0.5 % serum) were assessed. BrdU incorporation and expression of podocyte
      specific markers were employed as measures of cellular proliferation and
      differentiation, respectively. qPCR was used to verify expression of EPO receptor
      in cultured podocytes. RESULTS: Cellular adhesion was similar on all ECM proteins
      and unaffected by EPO. Proliferation was accelerated by laminin and the ECM
      extract, but the final cell density was similar on all ECM surfaces. Collagen IV
      supported the serum-deprived cells better than the other ECM proteins. EPO (2-20
      ng/ml) improved viability of serum-deprived podocytes on collagen I, collagen IV,
      and ECM, but not on laminin or bare plastic. The cells expressed mRNA for EPO
      receptor. CONCLUSION: The physiological ECM proteins are more supportive of
      primary podocytic cultures compared with collagen I. The protective effects of
      EPO during serum deprivation are modulated by the cultivation surface.

PMID- 24685987
TI  - PKB/SGK-resistant GSK-3 signaling following unilateral ureteral obstruction.
AB  - BACKGROUND/AIMS: Renal tissue fibrosis contributes to the development of end
      stage renal disease. Causes for renal tissue fibrosis include obstructive
      nephropathy. The development of renal fibrosis following unilateral ureteral
      obstruction (UUO) is blunted in gene-targeted mice lacking functional serum- and
      glucocorticoid-inducible kinase SGK1. Similar to Akt isoforms, SGK1
      phosphorylates and thus inactivates glycogen synthase kinase GSK-3. The present
      study explored whether PKB/SGK-dependent phoshorylation of GSK-3alpha/beta
      impacts on pro-fibrotic signaling following UUO. METHODS: UUO was induced in mice
      carrying a PKB/SGK-resistant GSK-3alpha/beta (gsk-3(KI)) and corresponding wild
      type mice (gsk-3(WT)). Three days after the obstructive injury, expression of
      fibrosis markers in kidney tissues was analyzed by quantitative RT-PCR and
      western blotting. RESULTS: GSK-3alpha and GSK-3beta phosphorylation was absent in
      both, the non-obstructed and the obstructed kidney tissues from gsk-3(KI) mice
      but was increased by UUO in kidney tissues from gsk-3(WT) mice. Expression of
      alpha-smooth muscle actin, type I collagen and type III collagen in the non
      obstructed kidney tissues was not significantly different between gsk-3(KI) mice
      and gsk-3(WT) mice but was significantly less increased in the obstructed kidney
      tissues from gsk-3(KI) mice than from gsk-3(WT) mice. After UUO treatment, renal
      beta-catenin protein abundance and renal expression of the beta-catenin sensitive
      genes: c-Myc, Dkk1, Twist and Lef1 were again significantly less increased in
      kidney tissues from gsk-3(KI) mice than from gsk-3(WT) mice. CONCLUSIONS: PKB/SGK
      dependent phosphorylation of glycogen synthase kinase GSK-3 contributes to the
      pro-fibrotic signaling leading to renal tissue fibrosis in obstructive
      nephropathy.

PMID- 24685988
TI  - Preferential silent survival of intracellular bacteria in hemoglobin-primed
      macrophages.
AB  - Hemolysis releases hemoglobin (Hb), a prooxidant, into circulation. While the
      heme iron is a nutrient for the invading pathogens, it releases ROS, which is
      both microbicidal and cytotoxic, making it a double-edged sword. Previously, we
      found a two-pass detoxification mechanism involving the endocytosis of Hb into
      monocytes in collaboration with vascular endothelial cells to overcome oxidative
      damage. This prompted us to examine the effect of Hb priming on host cell
      viability and intracellular bacterial clearance during a hemolytic infection.
      Here, we demonstrate that Hb-primed macrophages harbor a higher intracellular
      bacterial load but with suppressed apoptosis. p-ERK and p-p38 MAPK were
      significantly downregulated, with concomitant impairment of Bax and downstream
      caspases. The Hb-primed cells harboring intracellular bacteria upregulated anti
      inflammatory IL-10 and downregulated proinflammatory TNF-alpha, which further
      enhanced the infectivity of the neighboring cells. Our findings suggest that
      opportunistic intracellular pathogens exploit the Hb-scavenging machinery of the
      host to silently persist within the circulating phagocytes by suppressing
      apoptosis while escaping immune surveillance.

PMID- 24685990
TI  - Does consistent piperacillin dosing result in consistent therapeutic
      concentrations in critically ill patients? A longitudinal study over an entire
      antibiotic course.
AB  - Piperacillin plasma concentrations are known to vary between critically ill
      patients. However, there are no comprehensive data on the variability of
      antibiotic concentrations within the same patient. The purpose of this study was
      to investigate the adequacy of dosing during an entire 7-day antibiotic course
      and to investigate the variability in antibiotic trough concentrations both
      between patients and within the same patient. Piperacillin trough concentrations
      were measured daily in critically ill patients with normal renal function. The
      drug assay was performed using UPLC-MS/MS. The pharmacokinetic/pharmacodynamic
      target was 100% fT>MIC of the Pseudomonas aeruginosa EUCAST breakpoint. Within-
      and between-patient variability were calculated as percent coefficient of
      variation (CV). Eleven patients treated for pneumonia were included in this
      nested prospective observational cohort study. The median (range) age was 67 (18
      79) years, weight was 75 (57-90)kg and BMI was 23.5 (22.3-26.4). The median
      (range) creatinine clearance on Day 1 of antibiotic treatment was 102 (62
      154)mL/min. Trough concentrations were variable, ranging from 4.9 mg/L to 98.0
      mg/L. A median CV of 40% for within-patient variability and 57% for between
      patient variability was found. Within-patient variability was inversely
      correlated with SOFA score (R = 0.65, P = 0.027) and APACHE II score on admission
      (R = 0.73, P = 0.009). In conclusion, piperacillin concentrations varied widely
      both between patients and within the same patient. Within-patient variability was
      inversely correlated with disease severity. Consistent dosing of
      piperacillin/tazobactam does not result in consistent piperacillin concentrations
      throughout the entire treatment period.

PMID- 24685991
TI  - Stanniocalcin-1 ameliorates lipopolysaccharide-induced pulmonary oxidative
      stress, inflammation, and apoptosis in mice.
AB  - Stanniocalcin-1 (STC1) is an endogenous glycoprotein whose anti-inflammatory
      effects occur through induction of uncoupling proteins to reduce oxidative
      stress. In this study, we tested the hypothesis that exogenous recombinant human
      STC1 (rhSTC1) protects against lipopolysaccharide (LPS)-induced acute lung injury
      in mice. Anesthetized C57BL/6 mice underwent intratracheal spraying of LPS (20
      ug/10 g body wt), and lung injury was assessed 24h later by analyzing pulmonary
      edema, bronchoalveolar lavage fluid, and lung histopathology. Lung inflammation,
      oxidative stress, and expression of STC1 and its downstream uncoupling protein 2
      (UCP2) were analyzed at specific time points. Expression of UCP2 was suppressed
      initially but was subsequently upregulated after STC1 elevation in response to
      intratracheal administration of LPS. Intratracheal rhSTC1 treatment 1h before or
      after LPS spraying significantly attenuated pulmonary inflammation, oxidative
      stress, cell apoptosis, and acute lung injury. Pretreatment with STC1 short
      interfering RNA 48 h before LPS spraying inhibited the expression of STC1 and
      UCP2 and significantly increased the extent of lung injury. These findings
      suggest that STC1 is an endogenous stress protein that may counteract LPS-induced
      lung injury by inhibiting the inflammatory cascade and inducing antioxidant and
      antiapoptotic mechanisms. However, the potential clinical application of STC1 and
      the direct linkage between UCP2 and LPS-induced lung injury remain to be further
      investigated.

PMID- 24685992
TI  - Protective effect of telmisartan against progressive oxidative brain damage and
      synuclein phosphorylation in stroke-resistant spontaneously hypertensive rats.
AB  - Previously, we reported that reactive oxygen species and signaling molecules of
      angiotensin II produced lipid peroxides, degenerated proteins, and injured DNA
      after cerebral ischemia in normotensive Wistar rats. Here, we investigated the
      long-term effect of the angiotensin II type I receptor blocker telmisartan on
      oxidative stress and hyperphosphorylated alpha-synuclein accumulation in stroke
      resistant spontaneously hypertensive rats (SHR-SR). At the age of 3 months, SHR
      SR were divided into 3 treatment groups: SHR-SR vehicle (SHR/Ve), SHR-SR low-dose
      telmisartan (.3 mg/kg/day) (SHR/low), and SHR-SR high-dose telmisartan (3
      mg/kg/day) (SHR/high). Immunohistologic analyses were conducted in these groups
      and Wistar rats at the age of 6, 12, and 18 months. The SHR/Ve group demonstrated
      more progressive increase in advanced glycation end product (AGE)-, 4-hydroxy-2
      nonenal (4-HNE)-, and phosphorylated alpha-synuclein (pSyn)-positive cells in the
      cerebral cortex and hippocampus compared with the Wistar group at 18 months.
      These expressions were reduced in the SHR/low group even without lowering blood
      pressure (BP), and expressions were dramatically suppressed in the SHR/high group
      with lowering of BP. These data suggest that persistent hypertension in SHR-SR
      strongly potentiate the markers of oxidative damage (AGEs and 4-HNE) and abnormal
      accumulation of pSyn, which were greatly suppressed by telmisartan in a dose
      dependent manner without and with lowering of BP. 

PMID- 24685993
TI  - Safety of intravenous tissue plasminogen activator administration with computed
      tomography evidence of prior infarction.
AB  - BACKGROUND: Prior stroke within 3 months excludes patients from thrombolysis;
      however, patients may have computed tomography (CT) evidence of prior infarct,
      often of unknown time of origin. We aimed to determine if the presence of a
      previous infarct on pretreatment CT is a predictor of hemorrhagic complications
      and functional outcomes after the administration of intravenous (IV) tissue
      plasminogen activator (tPA). METHODS: We retrospectively analyzed consecutive
      patients treated with IV tPA at our institution from 2009-2011. Pretreatment CTs
      were reviewed for evidence of any prior infarct. Further review determined if any
      hemorrhagic transformation (HT) or symptomatic intracerebral hemorrhage (sICH)
      were present on repeat CT or magnetic resonance imaging. Outcomes included sICH,
      any HT, poor functional outcome (modified Rankin Scale score of 4-6), and
      discharge disposition. RESULTS: Of 212 IV tPA-treated patients, 84 (40%) had
      evidence of prior infarct on pretreatment CT. Patients with prior infarcts on CT
      were older (median age, 72 versus 65 years; P=.001) and had higher pretreatment
      National Institutes of Health Stroke Scale scores (median, 10 versus 7; P=.023).
      Patients with prior infarcts on CT did not experience more sICH (4% versus 2%;
      P=.221) or any HT (18% versus 14%; P=.471). These patients did have a higher
      frequency of poor functional outcome at discharge (82% versus 50%; P<.001) and
      were less often discharged to home or inpatient rehabilitation center (61% versus
      73%; P=.065). CONCLUSIONS: Visualization of prior infarcts on pretreatment CT did
      not predict an increased risk of sICH in our study and should not be viewed as a
      reason to withhold systemic tPA treatment after clinically evident strokes within
      3 months were excluded.

PMID- 24685994
TI  - Relationship between magnetic resonance angiography-diffusion-weighted imaging
      mismatch and clinical outcome in endovascular treatment for acute ischemic
      stroke: subgroup analysis of the Recovery by Endovascular Salvage for Cerebral
      Ultra-acute Embolism--Japan Registry.
AB  - BACKGROUND: The presence or absence of the penumbra area is important when
      performing reperfusion therapy in patients with acute ischemic stroke. As a
      predictor of this penumbra area, magnetic resonance angiography (MRA)-diffusion
      weighted imaging (DWI) mismatch is attracting attention. The usefulness of MRA
      DWI mismatch (MDM) using the DWI-Alberta Stroke Program Early Computed Tomography
      Score (ASPECTS) in endovascular treatment (EVT) of patients with cerebral large
      vessel occlusion was evaluated. METHODS: Of 1442 patients registered in the
      Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Registry
      between July 1, 2010 and June 30, 2011 who presented to the hospital within 24
      hours of the onset of acute cerebral infarction because of cerebral large vessel
      occlusion, 188 patients who had internal carotid artery or middle cerebral artery
      occlusion and achieved recanalization with EVT were included. Of these, 71
      patients underwent intracranial EVT because intravenous recombinant tissue
      plasminogen activator therapy was ineffective. The associations between the
      presence or absence of MDM (MDM-positive [MDM-P], DWI-ASPECTS>=6; MDM-negative
      [MDM-N], DWI-ASPECTS<6) and 90-day prognosis (modified Rankin Scale [mRS]) and
      symptomatic intracranial hemorrhage (sICH) were examined. RESULTS: Of the 188
      patients analyzed, the time from symptom onset to admission was within 3 hours in
      143 patients, 3-8 hours in 36 patients, and 8 hours or more in 9 patients. The
      time from the onset was within 3 hours in 118 patients in the MDM-P and 25
      patients in the MDM-N cases. Favorable outcomes (mRS score<=2 at 90 days) were
      seen in 63 patients (53.4%) in the MDM-P group and 7 patients (28.0%) in the MDM
      N group, showing a significantly more favorable clinical outcome in the MDM-P
      group (P=.027). The incidence of sICH was significantly lower in the MDM-P group
      (MDM-P group 3.4%, MDM-P group 20.0%; P=.009). The time from the onset was 3-8
      hours in 29 patients in the MDM-P group and in 7 patients in the MDM-N group.
      Favorable outcomes were seen in 12 patients (41.4%) in the MDM-P group and 2
      patients (28.6%) in the MDM-N group, with no significant difference between the 2
      groups. No patients had sICH. The patients admitted 8 hours or more after the
      onset were all MDM-P. Five patients (55.6%) had a favorable outcome. CONCLUSIONS:
      This study demonstrated the safety and efficacy of EVT in MDM-P patients within 3
      hours of symptom onset. Although the ratio of patients who had a favorable
      outcome was high in the MDM-P patients admitted 3-8 hours after the onset, the
      difference was not significant.

PMID- 24685995
TI  - High blood pressure on admission in relation to poor outcome in acute ischemic
      stroke with intracranial atherosclerotic stenosis or occlusion.
AB  - BACKGROUND: Intracranial atherosclerotic stenosis is common in Asian, black, and
      Hispanic individuals. However, the management of blood pressure (BP) in the
      setting of acute stage in these patients is controversial. The present study aims
      to explore the relationship between BP on admission and outcomes in acute
      ischemic stroke patients with intracranial atherosclerotic stenosis or occlusion.
      METHODS: We prospectively registered consecutive cases of acute ischemic stroke
      from September 01, 2009, to August 31, 2011. Patients with severe intracranial
      stenosis or occlusion were included. Death or disability was followed up at the
      end of the third month. The multivariate logistic regression model was used to
      analyze the relationship between BP on admission and clinical outcomes. RESULTS:
      We included 215 cases, which accounted for 22.7% (215 of 946) of the total
      registered cases. The mean age was 60.44+/-13.23 years. The median time of
      symptoms onset to admission was 72 hours (2-270 hours). Patients with systolic
      blood pressure (SBP) of 120-159 mm Hg or diastolic BP of 70-89 mm Hg had the
      lowest death or disability. After adjustment of confounders, SBP of 160 mm Hg or
      more on admission was the independent predictor of death or disability at the
      third month (relative risk [RR], 2.89; 95% confidence interval [CI], 1.20-6.91).
      SBP less than 120 mm Hg on admission had a trend of increasing death or
      disability (RR, 1.96; 95% CI, .60-6.33). CONCLUSIONS: Higher BP on admission was
      associated with an increased risk of death or disability in patients with
      symptomatic intracranial artery stenosis or occlusion. It is reasonable that
      further studies on the effects of BP lowering in acute stroke include these
      patients.

PMID- 24685996
TI  - CAPABLE trial: a randomized controlled trial of nurse, occupational therapist and
      handyman to reduce disability among older adults: rationale and design.
AB  - BACKGROUND: As the population ages, it is increasingly important to test new
      models of care that improve life quality and decrease health costs. This paper
      presents the rationale and design for a randomized clinical trial of a novel
      interdisciplinary program to reduce disability among low income older adults
      based on a previous pilot trial of the same design showing strong effect.
      METHODS: The CAPABLE (Community Aging in Place, Advancing Better Living for
      Elders) trial is a randomized controlled trial in which low income older adults
      with self-care disability are assigned to one of two groups: an interdisciplinary
      team of a nurse, occupational therapist, and handyman to address both personal
      and environmental risk factors for disability based on participants' functional
      goals, or an attention control of sedentary activities of choice. Both groups
      receive up to 10 home visits over 4 months. OUTCOMES: The primary outcome is
      decreased disability in self-care (ADL). Secondary outcomes are sustained
      decrease in self care disability as well as improvement in instrumental ADLS,
      strength, balance, walking speed, and health care utilization. Careful cost
      tracking and analysis using intervention data and claims data will enable direct
      measurement of the cost impact of the CAPABLE approach. CAPABLE has the potential
      to leverage current health care spending in Medicaid waivers, Accountable Care
      Organizations and other capitated systems to save the health care system costs as
      well as improving low income older adults' ability to age at home with improved
      life quality.

PMID- 24685997
TI  - Delta Healthy Sprouts: a randomized comparative effectiveness trial to promote
      maternal weight control and reduce childhood obesity in the Mississippi Delta.
AB  - INTRODUCTION: Excessive and inadequate gestational weight gain can complicate a
      woman's pregnancy and put her and her child at risk for poor delivery and birth
      outcomes. Further, feeding and activity habits established early in life can
      significantly impact the development of childhood obesity. METHODS: The on-going
      Delta Healthy Sprouts Project is a randomized, controlled, comparative trial
      testing the efficacy of two Maternal, Infant, and Early Childhood Home Visiting
      programs on weight status and health behaviors of 150 mothers and their infants
      residing in the rural Mississippi Delta region of the United States. Women are
      enrolled in their second trimester of pregnancy and randomized to one of two
      treatment arms. The control arm curriculum is based on Parents as Teachers, an
      evidence based approach to increase parental knowledge of child development and
      improve parenting practices. The experimental arm, labeled Parents as Teachers
      Enhanced, builds upon the control curriculum by including culturally tailored
      nutrition and physical activity components specifically designed for the
      gestational and postnatal periods. We hypothesize that, as compared to the
      control arm, the experimental arm will be more effective in preventing
      inappropriate gestational weight gain, reducing postnatal weight retention, and
      decreasing infant obesity rates. We also will evaluate mother and child dietary
      and physical activity outcomes, breastfeeding initiation and continuation, and
      child feeding practices. CONCLUSION: The Delta Healthy Sprouts Project tests a
      novel, combined approach to maternal weight management and childhood obesity
      prevention in pregnant women and their children at high risk for obesity and
      chronic disease.

PMID- 24685998
TI  - Reducing cardiovascular disease risk in mid-life and older African Americans: a
      church-based longitudinal intervention project at baseline.
AB  - INTRODUCTION: African Americans (AAs) experience higher age-adjusted morbidity
      and mortality than Whites for cardiovascular disease (CVD). Church-based health
      programs can reduce risk factors for CVD, including elevated blood pressure [BP],
      excess body weight, sedentary lifestyle and diet. Yet few studies have
      incorporated older adults and longitudinal designs. PURPOSES: The aims of this
      study are to: a) describe a theory-driven longitudinal intervention study to
      reduce CVD risk in mid-life and older AAs; b) compare selected dietary (fruit and
      vegetable servings/day, fat consumption), physical activity (PA) and clinical
      variables (BMI, girth circumferences, systolic and diastolic BP, LDL, HDL, total
      cholesterol [CHOL] and HDL/CHOL) between treatment and comparison churches at
      baseline; c) identify selected background characteristics (life satisfaction,
      social support, age, gender, educational level, marital status, living
      arrangement and medication use) at baseline that may confound results; and d)
      share the lessons learned. METHODS: This study incorporated a longitudinal
      pre/post with comparison group quasi-experimental design. Community-based
      participatory research (CBPR) was used to discover ideas for the study, identify
      community advisors, recruit churches (three treatment, three comparison) in two
      counties in North Florida, and randomly select 221 mid-life and older AAs (45+)
      (n=104 in clinical subsample), stratifying for age and gender. Data were
      collected through self-report questionnaires and clinical assessments. RESULTS
      AND CONCLUSIONS: Dietary, PA and clinical results were similar to the literature.
      Treatment and comparison groups were similar in background characteristics and
      health behaviors but differed in selected clinical factors. For the total sample,
      relationships were noted for most of the background characteristics. Lessons
      learned focused on community relationships and participant recruitment.

PMID- 24685999
TI  - Systematic structural characterization of metabolites in Arabidopsis via
      candidate substrate-product pair networks.
AB  - Plant metabolomics is increasingly used for pathway discovery and to elucidate
      gene function. However, the main bottleneck is the identification of the detected
      compounds. This is more pronounced for secondary metabolites as many of their
      pathways are still underexplored. Here, an algorithm is presented in which liquid
      chromatography-mass spectrometry profiles are searched for pairs of peaks that
      have mass and retention time differences corresponding with those of substrates
      and products from well-known enzymatic reactions. Concatenating the latter peak
      pairs, called candidate substrate-product pairs (CSPP), into a network displays
      tentative (bio)synthetic routes. Starting from known peaks, propagating the
      network along these routes allows the characterization of adjacent peaks leading
      to their structure prediction. As a proof-of-principle, this high-throughput
      cheminformatics procedure was applied to the Arabidopsis thaliana leaf metabolome
      where it allowed the characterization of the structures of 60% of the profiled
      compounds. Moreover, based on searches in the Chemical Abstract Service database,
      the algorithm led to the characterization of 61 compounds that had never been
      described in plants before. The CSPP-based annotation was confirmed by
      independent MS(n) experiments. In addition to being high throughput, this method
      allows the annotation of low-abundance compounds that are otherwise not amenable
      to isolation and purification. This method will greatly advance the value of
      metabolomics in systems biology. 

PMID- 24686000
TI  - The structure of the geriatric depressed brain and response to electroconvulsive
      therapy.
AB  - Electroconvulsive therapy (ECT) is the treatment of choice in severe geriatric
      depression. High remission rates may be influenced by specific brain morphology
      characteristic of geriatric depression. Our objective was to identify the
      relationship between brain structure, symptom profile, and ECT response. In a
      naturalistic cohort of 55 patients with a major depressive disorder, structural
      magnetic resonance imaging (MRI) was performed before ECT. Voxel-based
      morphometry was applied to determine regional differences in gray matter (GM)
      volume between patients and 23 matched healthy controls. Depressed patients with
      psychotic symptoms showed significantly higher remission rates and smaller
      regional GM volume of the left inferior frontal gyrus (IFG). Patients with late
      onset depression showed smaller regional GM volume of the bilateral lateral
      temporal cortex. Larger size of response in the whole patient group was related
      to smaller pretreatment regional GM volume of the right lateral temporal cortex,
      whereas faster speed of response was related to smaller pretreatment regional GM
      volume of the right IFG. ECT is most effective in depressed patients with
      psychotic symptoms. In this study the presence of psychotic symptoms was related
      to pretreatment smaller GM volume of the left IFG and bilateral temporal cortex.
      Smaller volume of the IFG pretreatment was related to faster treatment response,
      and smaller volume of the right lateral temporal cortex pretreatment was related
      to larger response to ECT. These results are possibly explained by the
      connectivity between these brain regions and an interconnected network that is
      particularly activated by the ECT-induced seizures. 

PMID- 24686002
TI  - Distortion of a transcatheter aortic valve after external chest compression.

PMID- 24686001
TI  - Mid-term results of aortic valve surgery in redo scenarios in the current
      practice: results from the multicentre European RECORD (REdo Cardiac Operation
      Research Database) initiative?.
AB  - OBJECTIVES: Although commonly reported as single-centre experiences, redo aortic
      valve replacement (RAVR) has overall acceptable results. Nevertheless, trans
      catheter aortic valve replacement has recently questioned the efficacy of RAVR.
      METHODS: Early-to-mid-term results and determinants of mortality in 711 cases of
      RAVR from seven European institutions were assessed in the entire population and
      in selected high-risk subgroups [elderly >75 years, urgent/emergent procedures,
      preoperative New York Heart Association (NYHA) functional Class IV and
      endocarditis]. RESULTS: Hospital mortality was 5.1%, major re-entry
      cardiovascular complications (MRCVCs) 4.9%, low cardiac output syndrome (LCOS)
      15.3%, stroke 6.6%, acute respiratory failure (ARF) 10.6%, acute renal
      insufficiency (ARI) 19.3% and need for continuous renal replacement therapy
      (CRRT) 7.2%, transfusions 66.9% and for permanent pacemaker (PMK) 12.7%. Mid-term
      survival, freedom from acute heart failure (AHF), reinterventions, stroke and
      thrombo-embolisms were 77.2 +/- 2.7, 84.4 +/- 2.6, 97.2 +/- 0.8, 97.2 +/- 0.9 and
      96.3 +/- 1.2%, respectively; 87.5% of patients were in NYHA functional Class I
      II. Preoperative left ventricular ejection fraction of <30% [odds ratio (OR) 8.7,
      95% confidence interval (CI) 2.1-35.6], MRCVCs (OR 20.9, 95% CI 5.6-78.3),
      cardiopulmonary bypass time (OR 1.1, 95% CI 1.0-1.1), perioperative LCOS (OR
      17.2, 95% CI 5.1-57.4) and ARI (OR 5.1, 95% CI 1.5-18.1) predicted hospital
      death. Endocarditis (OR 7.5, 95% CI 2.9-19.1), preoperative NYHA functional Class
      IV (OR 4.7, 95% CI 1.0-24.0), combined RAVR + mitral surgery (OR 5.1, 95% CI 1.5
      17.3) and AHF at follow-up (OR 2.8, 95% CI 1.3-6.0) predicted late death at the
      Cox proportional hazard regression model. Elderly >75 years had similar hospital
      mortality (P = 0.06) and major morbidity, except for a higher need for PMK (P =
      0.03), as well as comparable mid-term survival (P = 0.89), freedom from AHF (P =
      0.81), reinterventions (P = 0.63), stroke (P = 0.21) and thrombo-embolisms (P =
      0.09). Urgent/emergent indication resulted in higher hospital death, LCOS,
      transfusions, MRCVCs, intra-aortic balloon pumping (IABP), stroke, prolonged (>48
      h) ventilation, pneumonia, ARI, CRRT, lower mid-term survival and freedom from
      AHF (P <= 0.03). Preoperative NYHA functional Class IV correlated with higher
      LCOS, IABP, prolonged ventilation, pneumonia, ARF, ARI, CRRT and MRCVCs and lower
      mid-term survival, freedom from AHF, reinterventions and stroke (P <= 0.02).
      Endocarditis demonstrated higher hospital mortality, MRCVCs, LCOS, IABP, stroke,
      ARF, prolonged intubation, pneumonia, ARI, CRRT, transfusions and PMK and lower
      mid-term survival and freedom from AHF and reinterventions (P <= 0.04).
      CONCLUSIONS: RAVR achieves overall satisfactory results. Baseline risk factors
      and perioperative complications strongly affect outcomes and mandate improvements
      in perioperative management. New emerging strategies might be considered in
      selected high-risk cases.

PMID- 24686003
TI  - Searching for the second best graft for coronary artery bypass surgery: a network
      meta-analysis of randomized controlled trials?.
AB  - OBJECTIVES: There is a lack of unequivocal evidence basis for selecting the best
      second conduit in coronary artery bypass grafting (CABG). We thus aimed to
      perform head-to-head relative effect estimate on angiographic outcomes for second
      conduits, including the right internal mammary artery (RIMA), radial artery (RA),
      right gastroepiploic artery (RGEA) and saphenous vein graft (SVG) by means of
      network meta-analysis of randomized controlled trials (RCTs). METHODS: Databases
      were searched for RCTs comparing angiographic outcomes (>=4 weeks) of second
      conduits in CABG. Odds ratios (95% confidence intervals) were computed with
      Markov Chain Monte Carlo simulation. RESULTS: A total of nine RCTs were
      identified, including 2780 patients and 1620 angiographic results available for
      analysis to compare RIMA (n=145) versus RA (n=871) versus RGEA (n=92) versus SVG
      (n=845). The mean time to angiographic follow-up ranged from 1 to 7.7 years. An
      SVG was significantly associated with a 4-fold (1.67-16.00) and 3-fold (0.78
      22.20) increased risk of late (>=4 years) functional graft occlusion when
      compared with the RIMA and RA, respectively. A RIMA was associated with a non
      significant 27% absolute risk reduction for functional graft occlusion when
      compared with the RA. CONCLUSIONS: The present network meta-analysis consistently
      demonstrated an angiographic superiority of RIMA and RA over SVG. The RIMA is
      expected to achieve a better patency rate than the RA, but further studies are
      needed.

PMID- 24686004
TI  - Direct electrochemistry of cytochrome c immobilized on gold electrode surface via
      Zr(IV) ion glue and its activity for ascorbic acid.
AB  - Direct electrochemistry of cytochrome c (Cyt c) is achieved via Zr(IV) ion as an
      immobilization matrix to interface Cyt c on gold surface via thiol self-assembled
      monolayers. Steps of surface modification and electrocatalytic activity of the
      immobilized Cyt c are followed by voltammetry, impedance spectroscopy,
      chronoampetrometry, and attenuated total reflectance Fourier transform infrared
      (ATR-FTIR) spectroscopy. The results indicate that the native structure of Cyt c
      is conserved during the immobilization process. The immobilization method is
      rather simple, effective and free of immobilizing activators and reagents. Direct
      electron transfer rate constant and surface coverage of the immobilized Cyt c are
      found as 8.62(+/-1.98) s(-1) and 1.15(+/-0.38)*10(-11)molcm(-2), respectively.
      Bioactivity studies of the immobilized Cyt c toward oxidation of the ascorbic
      acid (AA) substrate show a linear response, from 10.0MUM to 1.30mM AA, with a
      detection limit of 5.0(+/-1.8) MUM AA and mean relative standard deviations
      varied from 13.7% to 3.7% for n=4 at each point. A value of 1.6(+/-0.8) mM AA is
      found for the Michaelis-Menten constant of Au-MPA-Zr(IV)-Cyt c toward AA for the
      first time. The tightly immobilized Cyt c maintains its bioactivity for more than
      32days storage at 4 degrees C. 

PMID- 24686005
TI  - Effects of angiotensin converting enzyme inhibitors and angiotensin receptor
      blockers in contrast-induced nephropathy.
AB  - Contrast-induced nephropathy (CIN) is considered the third leading cause of
      iatrogenic acute kidney injury in high-risk patients undergoing radiographic
      procedures. The main mechanism leading to CIN is medullary hypoxia due to
      decreased renal blood flow, secondary to renal artery vasoconstriction and direct
      tubular toxicity by contrast medium. Furthermore, experimental data suggests that
      an activated renin-angiotensin-aldosterone system (RAAS) plays a role in the
      pathophysiology of CIN. However, the role of RAAS blockers, including angiotensin
      converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in
      CIN is controversial. They have been reported to be effective in the prevention
      of CIN in previous studies, but some studies have concluded that they were
      associated with an increased risk of CIN, especially in patients with pre
      existing renal impairment. In summary, there is no solid data to link ACE
      inhibitors and ARB to CIN, and larger randomised controlled trials are necessary
      to further investigate their role in the development of CIN. In this review, we
      discuss the pathophysiology of CIN, the role of RAAS on the development of CIN,
      and the effect of RAAS blockers on CIN.

PMID- 24686006
TI  - Superior activity of a new histone deacetylase inhibitor (ZYJ-34c) in inhibiting
      growth of human leukemia cells by inducing p21WAF1 expression and cell cycle
      arrest.
AB  - Histone deacetylase inhibitors are a new class of anticancer agents that inhibit
      cancer cell proliferation and induce apoptosis and cell cycle arrest in various
      cancer cells. Recently, we identified ZYJ-34c, a modified histone deacetylase
      inhibitor that showed significantly higher antitumor activity in vivo than the
      FDA-approved drug suberoylanilide hydroxamic acid. We aimed to investigate its
      exact mechanism of action. Activity of ZY-34c against human erythroleukemic
      (K562) cells, human myeloid leukemia (HL-60) cells, and primary leukemic cells
      were investigated in vitro using proliferation assays, cell cycle assays,
      apoptosis assays, RNA interference, promoter acetylation assays, and assays of
      transcription of related molecules. ZYJ-34c strongly inhibited the proliferation
      of leukemia cells compared with suberoylanilide hydroxamic acid. Primary leukemic
      cells isolated from patients with acute myeloid leukemia were more sensitive to
      ZYJ-34c. The 50% growth-inhibitory concentrations of ZYJ-34c and suberoylanilide
      hydroxamic acid were 2.95+/-0.75 and 4.45+/-0.29 MUmol/l for K562 cells treated
      for 48 h, respectively. We found that ZYJ-34c caused more significant G1 cell
      cycle arrest than suberoylanilide hydroxamic acid, in a time-dependent manner.
      ZYJ-34c-induced hyperacetylation of histone H3 and H4 around the promoter region
      of p21. P21 RNA interference markedly impaired ZYJ-34c-induced or suberoylanilide
      hydroxamic acid-induced G1 cell cycle arrest. In addition, levels of bcr-abl mRNA
      and protein in K562 cells decreased after treatment with either suberoylanilide
      hydroxamic acid or ZYJ-34c; moreover, ZYJ-34c had a higher inhibition activity.
      ZYJ-34c could represent a novel pharmacological agent with potential benefit for
      patients with leukemia. 

PMID- 24686007
TI  - MiR-489 modulates cisplatin resistance in human ovarian cancer cells by targeting
      Akt3.
AB  - MicroRNAs are a conserved class of small noncoding RNA molecules that harbour the
      capacity to regulate protein-coding gene expression at the post-transcriptional
      level. In the current study, we show that miR-489 is downregulated in cisplatin
      (CDDP)-resistant ovarian cancer cells, SKOV3/CDDP and OVCAR3/CDDP cells. MiR-489
      overexpression results in an inhibition of SKOV3 and OVCAR3 cell survival and
      cell growth after CDDP treatment and an induction of cell apoptosis. Inhibition
      of miR-489 yields the opposite results. In addition, miR-489 overexpression
      increases the sensitivity of SKOV3/CDDP and OVCAR3/CDDP cells to CDDP and
      inhibits their colony number. Akt3 is validated as a direct target of miR-489 in
      SKOV3, OVCAR3, SKOV3/CDDP and OVCAR3/CDDP cells. In addition, miR-489 suppresses
      Akt3 protein expression by binding sites on its 3'UTR. Knockdown of Akt3 results
      in a similar effect as that because of miR-489 overexpression; importantly, Akt3
      silencing rescues the functions induced by miR-489. Furthermore, we also use the
      Akt3 inhibitor, MK-2206 2HCl, to determine the role of Akt3 in CDDP resistance.
      Our study showed that MK-2206 2HCl increased the sensitivity of SKOV3/CDDP and
      OVCAR3/CDDP cells to CDDP. Taken together, our results indicate that miR-489
      inhibited CDDP resistance and cell growth, and promotes apoptosis by suppressing
      Akt3 expression. Furthermore, the identification of a novel miR-489-based pathway
      in CDDP-resistant ovarian cancer will facilitate the development of therapeutic
      strategies. 

PMID- 24686008
TI  - An alternative transcription start site yields estrogen-unresponsive Kiss1 mRNA
      transcripts in the hypothalamus of prepubertal female rats.
AB  - The importance of the Kiss1 gene in the control of reproductive development is
      well documented. However, much less is known about the transcriptional regulation
      of Kiss1 expression in the hypothalamus. Critical for these studies is an
      accurate identification of the site(s) where Kiss1 transcription is initiated.
      Employing 5'-RACE PCR, we detected a transcription start site (TSS1) used by the
      hypothalamus of rats, mice, nonhuman primates and humans to initiate Kiss1
      transcription. In rodents, an exon 1 encoding 5'-untranslated sequences is
      followed by an alternatively spliced second exon, which encodes 5'-untranslated
      regions of two different lengths and contains the translation initiation codon
      (ATG). In nonhuman primates and humans, exon 2 is not alternatively spliced.
      Surprisingly, in rat mediobasal hypothalamus (MBH), but not preoptic area (POA),
      an additional TSS (TSS2) located upstream from TSS1 generates an exon 1 longer
      (377 bp) than the TSS1-derived exon 1 (98 bp). The content of TSS1-derived
      transcripts increased at puberty in the POA and MBH of female rats. It also
      increased in the MBH after ovariectomy, and this change was prevented by
      estrogen. In contrast, no such changes in TSS2-derived transcript abundance were
      detected. Promoter assays showed that the proximal TSS1 promoter is much more
      active than the putative TSS2 promoter, and that only the TSS1 promoter is
      regulated by estrogen. These differences appear to be related to the presence of
      a TATA box and binding sites for transcription factors activating transcription
      and interacting with estrogen receptor-alpha in the TSS1, but not TSS2, promoter.

PMID- 24686009
TI  - Role of arterial telomere dysfunction in hypertension: relative contributions of
      telomere shortening and telomere uncapping.
AB  - OBJECTIVE: Telomere shortening in arteries could lead to telomere uncapping and
      cellular senescence, which in turn could promote the development of hypertension.
      METHODS AND RESULTS: To assess the novel role of arterial telomere dysfunction in
      hypertension, we compared mean telomere length (qPCR), telomere uncapping (serine
      139 phosphorylated histone gamma-H2A.X (gamma-H2) localized to telomeres: ChIP),
      and tumor suppressor protein p53 (P53)/cyclin-dependent kinase inhibitor 1A (P21)
      induced senescence (P53 bound to P21 gene promoter: ChIP) in arteries from 55 age
      matched hypertensive and nonhypertensive individuals. Arterial mean telomere
      length was not different in hypertensive patients compared with nonhypertensive
      individuals (P = 0.29). Arterial telomere uncapping and P53/P21-induced
      senescence were two-fold greater in hypertensive patients compared with
      nonhypertensive individuals (P = 0.04 and P = 0.02, respectively). Arterial mean
      telomere length was not associated with telomere uncapping or P53/P21-induced
      senescence (r = -0.02, P = 0.44 and r = 0.01, P = 0.50, respectively), but
      telomere uncapping was a highly influential covariate for the hypertension group
      difference in P53/P21-induced senescence (r = 0.62, P < 0.001, eta(p)(2) = 0.35).
      Finally, telomere uncapping was a significant predictor of hypertension status (P
      = 0.03), whereas mean telomere length was not (P = 0.68). CONCLUSION:
      Collectively, these findings demonstrate that arterial telomere uncapping and
      P53/P21-induced senescence are linked to hypertension independently of mean
      telomere length, and telomere uncapping influences hypertension status more than
      mean telomere length.

PMID- 24686010
TI  - Design, synthesis and biological evaluation of small-azo-dyes as potent Vesicular
      Glutamate Transporters inhibitors.
AB  - Vesicular Glutamate Transporters (VGLUTs) allow the loading of presynapic
      glutamate vesicles and thus play a critical role in glutamatergic synaptic
      transmission. VGLUTs have proved to be involved in several major neuropathologies
      and directly correlated to clinical dementia in Alzheimer and Parkinson's
      disease. Accordingly VGLUT represent a key biological target or biomarker for
      neuropathology treatment or diagnostic. Yet, despite the pivotal role of VGLUTs,
      their pharmacology appears quite limited. Known competitive inhibitors are
      restricted to some dyes as Trypan Blue (TB) and glutamate mimics. This lack of
      pharmacological tools has heavily hampered VGLUT investigations. Here we report a
      rapid access to small molecules that combine benefits of TB and dicarboxylic
      quinolines (DCQs). Their ability to block vesicular glutamate uptake was
      evaluated. Several compounds displayed low micromolar inhibitory potency when
      size related compounds are thirty to forty times less potent (i.e. DCQ). We then
      confirmed the VGLUT selectivity by measuring the effect of the series on
      vesicular monoamine transport and on metabotropic glutamate receptor activity.
      These inhibitors are synthesized in only two steps and count among the best
      pharmacological tools for VGLUTs studies. 

PMID- 24686011
TI  - Biological evaluation of new mimetics of annonaceous acetogenins: alteration of
      right scaffold by click linkage with aromatic functionalities.
AB  - A small library of analogues of annonaceous acetogenins through click linkage
      with aromatic moieties is established using a convergent modular fragment
      assembly approach. These analogues exhibited low micromolar inhibitory activities
      against the proliferation of several human cancer cell lines. Structure-activity
      relationship (SAR) of these analogues indicates that replacement of the methoxy
      groups of ubiquinone ring with methyl groups is proved to be a useful strategy
      for improving the anticancer activity of quinone-acetogenin hybrids. 

PMID- 24686012
TI  - PMPA and PMEA prodrugs for the treatment of HIV infections and human
      papillomavirus (HPV) associated neoplasia and cancer.
AB  - The synthesis and in vitro biological evaluation of novel phosphonamidate and
      phosphonodiamidate prodrugs of adefovir and tenofovir are reported. The selected
      synthetic approach from free phosphonic acid via bis-trimethylsilyl ester
      intermediates affords (L)-alanine ester derivatives in 10-70% yields. When
      assessed for their anti-HIV activity, all the prodrugs showed submicromolar
      activity. Noteworthy, the most potent derivative in the adefovir series contained
      a 5,6,7,8-tetrahydronaphtyl group, herein reported for the first time as an aryl
      moiety in a ProTide. A pronounced cytostatic activity of the above prodrugs is
      also reported. Selected compounds were tested for their antiproliferative
      activity against HPV-transformed cells and they were found significantly more
      active in comparison to their parent compounds. In this study a slightly improved
      activity of the adefovir derivatives over those of tenofovir was also noticed.
      However, no specificity for naturally HPV-transformed cell lines was observed.

PMID- 24686013
TI  - 2-Aryl-3H-indol-3-ones: synthesis, electrochemical behaviour and antiplasmodial
      activities.
AB  - The synthesis of indolone derivatives and their antiplasmodial activity in vitro
      against Plasmodium falciparum at the blood stage are described. The 2-aryl-3H
      indol-3-ones were synthesized via deoxygenation of indolone-N-oxides.
      Electrochemical behaviour, antiplasmodial activity and cytotoxicity on human
      tumor cell lines were compared to those of indolone-N-oxides. The antiplasmodial
      IC50 (concentrations at 50% inhibition) of these compounds ranged between 49 and
      1327 nM. Among them, the 2-(4-dimethylaminophenyl)-5-methoxy-indol-3-one, 7, had
      the best antiplasmodial activity in vitro (IC50 = 49 nM; FcB1 strain) and
      selectivity index (SI (CC50 MCF7/IC50 FcB1) = 423.4). Thus, the hits identified
      in this deoxygenated series correspond to their structural homologs in the N
      oxide series with comparable electrochemical behaviour at the nitrogen-carbon
      double bond. 

PMID- 24686014
TI  - Analogue-based design, synthesis and biological evaluation of 3-substituted
      (methylenehydrazono)indolin-2-ones as anticancer agents.
AB  - The docking studies on CDK2 and GSK-3beta inspired us to synthesis a series of
      indoline-2,3-dione hydrazones 10a-l. Treatment of indoline-2,3-dione derivatives
      7a-d with hydrazine gave 3-hydrazonoindolin-2-ones 8a-d which were reacted with
      the appropriate aldehydes 9a-c to yield 3-substituted-(methylenehydrazono)indolin
      2-ones 10a-l. Compounds 10a-l showed a significant anticancer activity against
      human breast cell line MCF-7. Compounds 10c, f, i exhibited the highest activity
      almost the same of doxorubicin (IC50 = 6.10 MUM) with IC50 = 7.75, 6.75, 6.25
      MUM, respectively. 

PMID- 24686015
TI  - Binuclear copper complexes: synthesis, X-ray structure and interaction study with
      nucleotide/protein by in vitro biochemical and electrochemical analysis.
AB  - Two new, binuclear copper(II) hydrazone complexes have been synthesized and
      characterized by various physico-chemical techniques including single crystal X
      ray diffraction. Interaction of these complexes with nucleotide and protein were
      analyzed by in vitro biochemical and electrochemical analysis. Both the complexes
      exhibited intercalative mode of binding with DNA. Further, gel electrophoresis
      assay demonstrated the ability of the complexes to cleave the supercoiled pBR322
      plasmid DNA to nicked circular DNA form. Cytotoxicity of the complexes performed
      against a panel of cancer cell lines and a normal cell line proved that these
      complexes are potentially cytotoxic against the cancerous cell lines,
      particularly with IC50 as low as 0.7 MUM against HeLa cell line. 

PMID- 24686016
TI  - Discovery of mixed type thymidine phosphorylase inhibitors endowed with
      antiangiogenic properties: synthesis, pharmacological evaluation and molecular
      docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II.
AB  - In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin
      4-ones were designed, synthesized and evaluated for their TP inhibitory
      potential. All the synthesized analogues conferred a varying degree of TP
      inhibitory activity, comparable or better than positive control, 7-deazaxanthine
      (7-DX, 2) (IC50 value = 42.63 MUM). A systematic approach to the lead
      optimization identified compounds 3c and 4a as the most promising TP inhibitors,
      exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds
      demonstrated the ability to attenuate the expression of the angiogenic markers
      (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In
      addition, molecular docking studies revealed the plausible binding orientation of
      these inhibitors towards TP, which was in accordance with the experimental
      results. Taken as a whole, these compounds would constitute a new direction for
      the design of novel TP inhibitors with promising antiangiogenic properties. 

PMID- 24686017
TI  - Searching for new derivatives of neocryptolepine: synthesis, antiproliferative,
      antimicrobial and antifungal activities.
AB  - A series of novel amino acid and dipeptide derivatives of neocryptolepine were
      synthesized and tested for their antimicrobial, antifungal and antiproliferative
      activity in vitro against cancer cell lines (KB, A549, MCF-7, LoVo) and normal
      mice fibroblast cells (BALB/3T3). Biological evaluation revealed that almost all
      of the new compounds displayed high antiproliferative activity against the tested
      cells and moderate to potent antibacterial activities. Interestingly, these
      compounds were active against Candida albicans biofilms at doses significantly
      lower than those required against free-floating planktonic fungal cells. The most
      promising compounds are derivatives with glycine and L-proline as a substituent
      both at 2 and at 9 position of 5H-indolo[2,3-b]quinoline. In general, these new
      compounds (2a, 3a, 6a and 7a) showed the highest dual action against cancer lines
      and infectious pathogenic microbes in vitro.

PMID- 24686018
TI  - Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H- and 11Me
      indolo[3,2-c]quinolines.
AB  - A series of 6-amino-11H- indolo[3,2-c]quinoline derivatives with various
      substituents on the quinoline ring were synthesized. A methyl group introduced to
      N-11 of the intermediate 4 to elaborate novel analog 7. The cytotoxic effect of
      these 6-amino-substituted 11H- and 11-methyl-indolo[3,2-c]quinoline derivatives
      in vitro were tested against MV4-11 (human leukemia), A549 (non-small cell lung
      cancer) and HCT116 (colon cancer) and BALB/3T3 (normal murine fibroblasts). All
      the N-11 methylated compounds significantly increased the cytotoxicity. Compound
      7p was most active with the IC50 value of 0.052 MUM against the MV4-11 cell line,
      and also exhibited a selective activity against A549, HCT116 and BALB/3T3 cell
      line, with the respective IC50 values of 0.112, 0.007 and 0.083 MUM, which were
      higher or comparable to those of the anticancer drug doxorubicin HCl. The binding
      constants of 5g and 7h to salmon fish sperm DNA were also evaluated using UV-vis
      absorption spectroscopy, indicating intercalation binding with constants of 1.05
      * 10(6) L/mol and 4.84 * 10(6) L/mol. 

PMID- 24686019
TI  - Pump and blow isn't hit or miss: the science of BLS education.

PMID- 24686020
TI  - Effects of a mandatory basic life support training programme on the no-flow
      fraction during in-hospital cardiac resuscitation: an observational study.
AB  - AIM OF THE STUDY: Many hospitals have basic life support (BLS) training
      programmes, but the effects on the quality of chest compressions are unclear.
      This study aimed to evaluate the no-flow fraction (NFF) during BLS provided by
      standard care nursing teams over a five-year observation period during which
      annual participation in the BLS training was mandatory. METHODS: All healthcare
      professionals working at Dresden University Hospital were instructed in BLS and
      automated external defibrillator (AED) use according to the current European
      Resuscitation Council guidelines on an annual basis. After each cardiac arrest
      occurring on a standard care ward, AED data were analyzed. The time without chest
      compressions during the period without spontaneous circulation (i.e., the no-flow
      fraction) was calculated using thoracic impedance data. RESULTS: For each year of
      the study period (2008-2012), a total of 1454, 1466, 1487, 1432, and 1388 health
      care professionals, respectively, participated in the training. The median no
      flow fraction decreased significantly from 0.55 [0.42; 0.57] (median [250/00;
      750/00]) in 2008 to 0.3 [0.28; 0.35] in 2012. Following revision of the BLS
      curriculum after publication of the 2010 guidelines, cardiac arrest was
      associated with a higher proportion of patients achieving ROSC (72% vs. 48%,
      P=0.025) but not a higher survival rate to hospital discharge (35% vs. 19%,
      P=0.073). CONCLUSION: The NFF during in-hospital cardiac resuscitation decreased
      after establishment of a mandatory annual BLS training for healthcare
      professionals. Following publication of the 2010 guidelines, more patients
      achieved ROSC after in-hospital cardiac arrest.

PMID- 24686021
TI  - Cardiac arrest from accidental hypothermia, a rare condition with potentially
      excellent neurological outcome, if you treat it right.

PMID- 24686022
TI  - ED visits and spending by unauthorized immigrants compared with legal immigrants
      and US natives.

PMID- 24686023
TI  - Hyperacute Guillain-Barre syndrome mimicking stroke: report of 3 cases: Guillain
      Barre and stroke.

PMID- 24686024
TI  - Troponin leak associated with drug-induced methemoglobinemia.
AB  - Drug-induced methemoglobinemia is a well-described entity but has not been
      previously associated with elevated troponins in the absence of cardiac symptoms.
      We report a case of a patient presenting to the emergency department (ED) with
      complaints related to an exacerbation of her long-standing cystitis. A low pulse
      oximetry reading prompted an evaluation, revealing a troponin leak, which peaked
      at 10 hours. Her methemoglobin level was found to be elevated at 11.4%, but a
      preexisting anemia apparently prevented the clinical recognition of cyanosis. The
      methemoglobinemia was determined to be secondary to her ingestion of
      phenazopyridine and trimethoprim-sulfa methoxizole. Although phenazopyridine and
      sulfa agents have long been known to cause methemoglobinemia, our patient
      exhibited an asymptomatic troponin leak that has not been previously reported as
      a complication of drug-induced methemoglobinemia. Clinicians should be aware of
      this potential association.

PMID- 24686025
TI  - Quick development and sudden death: Evans syndrome followed by thrombotic
      thrombocytopenic purpura.

PMID- 24686026
TI  - Compartment syndrome due to extravasation of contrast material: a case report.

PMID- 24686027
TI  - Necrotizing painful skin lesion after a mosquito bite in healthy elderly woman:
      case report.

PMID- 24686028
TI  - An enteric nervous system progenitor cell implant promotes a behavioral and
      neurochemical improvement in rats with a 6-OHDA-induced lesion.
AB  - The enteric nervous system (ENS) of mammals is derived from neural crest (NC)
      cells during embryogenesis and at the beginning of postnatal life. However,
      neural progenitor cells from the ENS (or ENSPC) are also found in the adult
      intestine and can be used for neuronal regeneration in diseases that lead to a
      loss of cell population, such as Parkinson's disease (PD), in which there is a
      decrease of dopaminergic neurons. The objective of this study was to evaluate the
      capacity of ENSPC to restore damaged nervous tissue and to show that they are
      functional for a behavioral and neurochemical recovery. We found that animals
      with ENSPC implants exhibited a motor recovery of 35% vs. the lesion group. In
      addition, DA levels were partially restored in 34%, while Homovanillic acid (HVA)
      levels remained at 21% vs. the group with a 6-Hydroxydopamine (6-OHDA)-induced
      lesion, suggesting that ENSPC represent a possible alternative in the study of
      cell transplants and the preservation of functional dopaminergic neurons in PD. 

PMID- 24686029
TI  - Single-dose, bilateral paravertebral block plus intravenous sufentanil analgesia
      in patients with esophageal cancer undergoing combined thoracoscopic-laparoscopic
      esophagectomy: a safe and effective alternative.
AB  - OBJECTIVE: Paravertebral block (PVB) has been shown to be an ideal aid for
      analgesia after thoracic or abdominal surgery. The authors studied the safety and
      efficacy of the single-dose and bilateral ultrasound-guided (USG)-PVB before
      combined thoracoscopic-laparoscopic esophagectomy (TLE) along with intravenous
      sufentanil analgesia as a method of pain relief in comparison with intravenous
      sufentanil as a sole analgesic agent. DESIGN: Prospective, randomized study.
      SETTING: Single university hospital. PARTICIPANTS: Fifty-two patients undergoing
      TLE. INTERVENTIONS: A USG-PVB was performed before surgery using a solution of 30
      mL of 0.5% ropivacaine by 3 injections of 10 mL each at the right T5 and
      bilateral T8 (PVB group, n=26) or the saline injection of 10 mL at every site
      (control group, n=26). MEASUREMENTS AND MAIN RESULTS: Successful PVBs were
      achieved in all patients of the PVB group. Intraoperative mean remifentanil usage
      and end-tidal sevoflurane concentration were lower in the PVB group (p<0.001).
      Hemodynamic parameters were stable in both groups. Postoperative pain scores both
      at rest and on coughing were lower during the first 8 hours in the PVB group than
      those in the control group (p<0.05). Cumulative sufentanil consumption delivered
      by patient-controlled analgesia (PCA) was significantly lower in the PVB group at
      all time points (p<0.05). Postoperative pulmonary function was better at the
      third postoperative day in the PVB group (p<0.05), with quicker hospital
      discharge and lower hospital costs (p<0.05). CONCLUSIONS: The single-dose and
      bilateral PVB given before TLE combined with sufentanil may provide better
      postoperative analgesia and early discharge in patients undergoing TLE.

PMID- 24686030
TI  - The involvement of accumbal glycine receptors in the dopamine-elevating effects
      of addictive drugs.
AB  - The ability of drugs of abuse to increase mesolimbic levels of dopamine is a
      characteristic associated with their rewarding effects. Exactly how these effects
      are produced by different substances is not as well characterised. Our previous
      work in rats has demonstrated that accumbal glycine receptors (GlyRs) are
      involved in mediating the dopamine-activating effects of ethanol, and in
      modulating ethanol intake. In this study the investigation of GlyR involvement
      was extended to include several different drugs of abuse. By using microdialysis
      and electrophysiology we compared effects of addictive drugs, with and without
      the GlyR antagonist strychnine, on dopamine levels and neurotransmission in
      nucleus accumbens. The dopamine-increasing effect of systemic ethanol and the
      drug-induced change in neurotransmission in vitro, as measured by microdialysis
      and field potential recordings, were dependent on GlyRs in nAc. Accumbal GlyRs
      were also involved in the actions of tetrahydrocannabinol and nicotine, but not
      in those of cocaine or morphine. These data indicate that accumbal GlyRs play a
      key role in ethanol-induced dopamine activation and contribute also to that of
      cannabinoids and nicotine.

PMID- 24686031
TI  - Observational study of decision making concerning radiotherapy in rectal cancer.
AB  - AIM: To understand how surgeons arrive at a decision in the complex and
      controversial field of radiotherapy in rectal cancer by identifying which
      variables are important in this decision and to assess the influence of age,
      training, area of practice and access to radiotherapy on decisions in this field.
      METHODS: A self-administered survey was distributed to 150 members of the CSSANZ.
      They were asked to rank the importance of 33 variables considered when making
      decisions to use radiotherapy in the treatment of rectal cancer. The responses
      were assessed for association of surgeon age, area of practise or access to
      radiotherapy with decisions in this field. RESULTS: A hierarchy of variables was
      produced which showed tumour characteristics had the highest average importance,
      higher than that attained by patient characteristics and side effects. There were
      subtle but statistically significant differences in the ranking of importance
      when surgeons were grouped by age, site of subspeciality training, site of
      practise and availability of radiotherapy service. CONCLUSION: This study
      identifies a hierarchy of variables used in decision making concerning
      radiotherapy in rectal cancer treatment, which may be used in heuristic decision
      making. Decisions on using radiotherapy are influenced by age, site of practise,
      site of training, and the presence of radiotherapy on site.

PMID- 24686032
TI  - Scolicidal effects of biogenic selenium nanoparticles against protoscolices of
      hydatid cysts.
AB  - Cystic echinococcosis (hydatid cyst, CE) as a zoonotic parasitic infection caused
      by the larval stage of the dog tapeworm Echinococcus granulosus is still an
      important economic and public health concern in the world. One of the treatment
      options for CE is surgical removal of the cysts combined with chemotherapy using
      albendazole and/or mebendazole before and after surgery. Currently, many
      scolicidal agents, which have some complications, have been used for inactivation
      of the cyst contents. Therefore the development of new scolicidal agents with low
      side effects and more efficacies is an urgent need for surgeons. The present
      study was aimed to investigate the in vitro scolicidal effect of selenium
      nanoparticles biosynthesized by a newly isolated marine bacterial strain Bacillus
      sp. MSh-1 against protoscoleces of E. granulosus. Protoscolices were aseptically
      aspirated from sheep livers having hydatid cysts. Various concentrations (50-500
      MUg/ml) of Se NPs (in size range of about 80-220 nm) were used for 10-60 min.
      Viability of protoscoleces was confirmed by 0.1% eosin staining. The results
      indicated that biogenic Se NPs at all concentrations have potent scolicidal
      effects especially at concentrations 500 and 250 MUg/ml after 10 and 20 min of
      application, respectively. In conclusion, the findings of present study proven
      that Se NPs have potent scolicidal effects, therefore may be used in CE surgery.
      However, the in vivo efficacy of these NPs remains to be explored.

PMID- 24686033
TI  - New criterion of asymptotic stability for delay systems with time-varying
      structures and delays.
AB  - In this paper, we study asymptotic stability of the zero solution of a class of
      differential systems governed by a scalar differential inequality with time
      varying structures and delays. We establish a new generalized Halanay inequality
      for the asymptotic stability of the zero solution for such systems under more
      relaxed conditions than the existing ones. We also apply the theoretical results
      to the analysis of self synchronization in networks of delayed differential
      systems and obtain a more general sufficient condition for self synchronization.

PMID- 24686034
TI  - Reference curve for the first-year growth response to growth hormone treatment in
      prepubertal children with idiopathic growth hormone deficiency: validation of the
      KIGS first-year growth response curve using the Belgian Register for the Study of
      Growth and Puberty Problems.
AB  - BACKGROUND: Comparing observed and expected growth after first-year growth
      hormone (GH) therapy is useful for identifying a poor growth response to GH. AIM:
      To generate a first-year, age-specific growth response reference curve for
      prepubertal Belgian children with idiopathic growth hormone deficiency (iGHD)
      treated with a standard weight-adjusted GH dose and to compare this national
      reference with the response references derived from KIGS. SUBJECTS AND METHODS:
      First-year height data of 357 prepubertal children (240 males) with iGHD were
      analyzed. Smooth reference curves of first-year height velocity (HV) in relation
      to age were created. Differences with the KIGS targets were evaluated after z
      score transformation. RESULTS: The observed first-year HVs were log-normal
      distributed by age and decreased significantly with age (p<0.001). No GH dose or
      gender effect was observed (p=0.5). Distance to target height, severity of GHD
      and occurrence of multiple pituitary hormone deficiencies had a positive effect
      (p<0.01) on the calculated HV SDS. When applying the KIGS targets for severe
      iGHD, mean HV SDS was close to zero (-0.09+/-0.84). CONCLUSION: The developed age
      specific growth response curves enable rapid identification of poor response to
      first-year GH treatment in prepubertal iGHD children. Our results validate the
      published growth targets derived from the KIGS database.

PMID- 24686035
TI  - Translational implications of the beta-cell epigenome in diabetes mellitus.
AB  - Diabetes mellitus is a disorder of glucose homeostasis that affects more than 24
      million Americans and 382 million individuals worldwide. Dysregulated insulin
      secretion from the pancreatic beta cells plays a central role in the
      pathophysiology of all forms of diabetes mellitus. Therefore, an enhanced
      understanding of the pathways that contribute to beta-cell failure is imperative.
      Epigenetics refers to heritable changes in DNA transcription that occur in the
      absence of changes to the linear DNA nucleotide sequence. Recent evidence
      suggests an expanding role of the beta-cell epigenome in the regulation of
      metabolic health. The goal of this review is to discuss maladaptive changes in
      beta-cell DNA methylation patterns and chromatin architecture, and their
      contribution to diabetes pathophysiology. Efforts to modulate the beta-cell
      epigenome as a means to prevent, diagnose, and treat diabetes are also discussed.

PMID- 24686036
TI  - Bisphenol A, obesity, and type 2 diabetes mellitus: genuine concern or
      unnecessary preoccupation?
AB  - Bisphenol A (BPA) is a ubiquitous industrial chemical found in a variety of
      plastic containers intended for food storage and in the epoxy resin linings of
      metal food and beverage cans, where it is used to prevent corrosion, food
      contamination, and spoilage. BPA has been linked recently to a wide variety of
      medical disorders and is known to have estrogenic activity with genomic as well
      as nongenomic estrogen receptor-mediated effects. Given the rapidly increasing
      prevalence rates of metabolic disorders such as obesity and type 2 diabetes, BPA
      has come under recent intense scrutiny in scientific and lay communities as a
      potential endocrine-disrupting compound with diabetogenic effects. The purpose of
      this review is to examine critically the available literature investigating the
      link between BPA and alterations in metabolic health. Typical levels of exposure
      to BPA in daily life are discussed, and both epidemiologic human data and
      mechanistic preclinical studies that have tested associations between BPA and
      obesity and diabetes are analyzed. Last, current policies and views of national
      and international regulatory agencies regarding the safety of BPA use are
      summarized.

PMID- 24686039
TI  - [Acute limping in children between 1 and 4 years old].
AB  - Recent limping in children aged between 1 and 4 years old are often a diagnostic
      problem because the young child may not be able to show the area of pain.
      Dominated by the traumatic causes like hairline fracture, the physician should
      eliminate the most severe, including infectious etiologies that require urgent
      treatment. The clinical examination is fundamental and simple complementary
      investigations like standard X-rays and biology (blood count cell, C reactive
      protein) looking for increased inflammatory parameters will help to find the
      cause in the majority of cases. The persistence of a limp beyond a week involves
      the realization of bone scan or MRI imaging.

PMID- 24686040
TI  - Monitoring sedation in patients receiving opioids for pain management.
AB  - Excessive sedation precedes opioid-induced respiratory depression. An evidence
      based practice project standardized systematic sedation monitoring by nurses
      using an opioid sedation scale and respiratory assessment when opioids are
      administered for pain management. Nurses were educated and documentation updated.
      Nurses demonstrated increased ability to identify at-risk patients (3.2 pre
      implementation; 3.6 post-implementation; 1-4 Likert scale) and reported
      understanding the tool to assess for oversedation (2.6 pre-implementation; 3.2
      post-implementation). Documentation compliance improved, and patient safety was
      maintained. 

PMID- 24686038
TI  - [Salt intake in children].
AB  - Very early in life, sodium intake correlates with blood pressure level. This
      warrants limiting the consumption of sodium by children. However, evidence
      regarding exact sodium requirements in that age range is lacking. This article
      focuses on the desirable sodium intake according to age as suggested by various
      groups of experts, on the levels of sodium intake recorded in consumption
      surveys, and on the public health strategies implemented to reduce salt
      consumption in the pediatric population. Practical recommendations are given by
      the Committee on nutrition of the French Society of Pediatrics in order to limit
      salt intake in children. 

PMID- 24686041
TI  - Is the hospital's magnet status linked to HCAHPS scores?
AB  - This study identified a significant link between Magnet hospitals and higher
      HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) scores
      across 110 Illinois hospitals. Compared with registered nurse nursing hours per
      patient-day and registered nurse turnover rate, Magnet status was a stronger
      contributor to the HCAHPS scores. A moderate to strong, reverse relationship
      between hospital's percentage of African American patients and HCAHPS scores
      suggests a need for strengthening culturally sensitive nurse-patient
      communications. 

PMID- 24686042
TI  - Is fever phobia driving inappropriate use of antipyretics?

PMID- 24686044
TI  - Human metapneumovirus viral load is an important risk factor for disease severity
      in young children.
AB  - BACKGROUND: The role of viral load in human metapneumovirus (HMPV) disease
      severity has not yet been clearly determined. OBJECTIVE: We evaluated the
      importance of viral load along with other factors in HMPV disease severity among
      children aged <3 years old. STUDY DESIGN: HMPV-positive cases were selected from
      a cohort of outpatients and hospitalized children with lower respiratory tract
      infections. HMPV groups (A or B) and viral loads were determined in their
      nasopharyngeal aspirates. Disease severity was defined by assessing risk for
      hospitalization and by using two validated clinical severity scores. RESULTS: Of
      the 118 HMPV cases detected over 4 years for which viral load could be
      determined, 60 belonged to genotype A and 58 to genotype B. Baseline
      characteristics were similar in HMPV-A and HMPV-B mono-infected patients. In
      multivariate analysis, HMPV hospitalization was associated with viral load >=1000
      copies/10(4)cells (OR, 3.2; 95%CI, 1.4-7.4), age <6 months (OR, 3.1; 95%CI, 1.2
      8.6) and presence of >=3 children in the household (OR, 2.7; 95%CI, 1.04-6.9). A
      high HMPV viral load was also associated with pulmonary rales (p=.03), use of
      bronchodilators (p=.02) and inhaled corticosteroids (p=.01). CONCLUSION: HMPV
      viral load is associated with disease severity in young children along with young
      age and household crowding.

PMID- 24686043
TI  - Defining criteria and resource use for high dependency care in children: an
      observational economic study.
AB  - OBJECTIVES: Internationally there is no consensus on defining and funding of
      paediatric high dependency care (HDC). This study tested whether a new UK
      Healthcare Resource Group (HRG) classification for HDC, with two categories of
      basic and advanced HDC, can identify children who consume greater staff resource.
      It also explored the impact of a change in basic HDC HRG criteria introduced in
      April 2011. DESIGN: Observational study of medical and nursing staff resource
      use. SETTING: 16 paediatric wards across 6 regional hospitals; 1 tertiary
      children's hospital (November 2010 to March 2011). PARTICIPANTS: 1098 infants and
      children admitted to paediatric wards. MAIN OUTCOME MEASURES: Number of children
      meeting criteria for basic and advanced HDC HRGs; care in a cubicle; medical and
      nursing staff costs, extrapolated from time spent at patient bedside. RESULTS:
      223 (20.3%) children met original HDC criteria (15.9% basic, 4.4% advanced). This
      fell to 88 (8.0%) with the change in basic HDC definition (3.6% basic, 4.4%
      advanced). Children who met original HDC criteria consumed greater bedside staff
      resource than those not meeting criteria (cost ratio 1.0:1.75:2.96 (non-HDC:basic
      HDC:advanced HDC)), with revised criteria identifying a (smaller) basic group
      with greater staff resource use (cost ratio 1.0:2.35:2.76). Being cared for in a
      cubicle was not associated with greater staff costs. CONCLUSIONS: HDC HRG
      criteria identify children who consume significantly greater staff resources.
      Revision of the definition has resulted in a large reduction of cases meeting the
      criteria but identifies a group consuming greater staff resources.

PMID- 24686037
TI  - Epigenetics of lung cancer.
AB  - Lung cancer is the leading cause of cancer-related mortality in the United
      States. Epigenetic alterations, including DNA methylation, histone modifications,
      and noncoding RNA expression, have been reported widely in the literature to play
      a major role in the genesis of lung cancer. The goal of this review is to
      summarize the common epigenetic changes associated with lung cancer to give some
      clarity to its etiology, and to provide an overview of the potential
      translational applications of these changes, including applications for early
      detection, diagnosis, prognostication, and therapeutics. 

PMID- 24686045
TI  - The effects of perineural versus intravenous dexamethasone on sciatic nerve
      blockade outcomes: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Perineural dexamethasone has been investigated as an adjuvant for
      brachial plexus nerve blocks, but it is not known whether the beneficial effect
      of perineural dexamethasone on analgesia duration leads to a better quality of
      surgical recovery. We hypothesized that patients receiving dexamethasone would
      have a better quality of recovery than patients not receiving dexamethasone. We
      also sought to compare the effect of perineural with that of IV dexamethasone on
      block characteristics. METHODS: Patients undergoing elective ankle and foot
      surgery were recruited over a 9-month period. Patients received ultrasound-guided
      sciatic nerve blocks by using 0.5% bupivacaine with epinephrine 1:300,000 (0.45
      mL/kg) and were randomized into 3 groups: group 1 = perineural dexamethasone 8
      mg/2 mL with 50 mL IV normal saline, group 2 = perineural saline/2 mL with IV 8
      mg dexamethasone in 50 mL normal saline, and group 3 = perineural saline/2 mL
      with 50 mL normal saline. The primary outcome was the global score in the quality
      of recovery (QoR-40). The secondary outcomes included analgesia duration, opioid
      consumption, patient satisfaction, numeric pain rating scores, and postoperative
      neurologic symptoms. RESULTS: Eighty patients were randomized, and 78 patients
      completed the study protocol. There was no improvement in the global QoR-40 score
      at 24 hours between the perineural dexamethasone and saline, median (97.5% CI)
      difference of -3 (-7 to 3); IV dexamethasone and saline, median difference of -1
      (-8 to 5); or perineural dexamethasone and IV dexamethasone median difference of 
      2 (-6 to 5). Analgesia duration (P < 0.001) and time to first toe movement (P <
      0.001) were prolonged by perineural dexamethasone compared with saline. IV
      dexamethasone prolonged time to first toe movement compared with saline (P =
      0.008) but not analgesia duration (P = 0.18). There was no significant difference
      in the time to first toe movement or analgesia duration between the perineural
      and IV dexamethasone groups. Postoperative opioid consumption was not different
      among study groups. Self-reported neurologic symptoms at 24 hours were not
      different among perineural dexamethasone (17, 63%), IV dexamethasone (10, 42%),
      or normal saline (8, 30%) (P = 0.31). All postoperative neurologic sequelae were
      resolved by 8 weeks. CONCLUSIONS: Preoperative administration of IV and
      perineural dexamethasone compared with saline did not improve overall QoR-40 or
      decrease opioid consumption but did prolong analgesic duration in patients
      undergoing elective foot and ankle surgery and receiving sciatic nerve block.
      Given the lack of clinical benefit and the concern of dexamethasone neurotoxicity
      as demonstrated in animal studies, the practice of perineural dexamethasone
      administration needs to be further evaluated.

PMID- 24686046
TI  - Ultrasound-guided supraclavicular brachial plexus block: single versus triple
      injection technique for upper limb arteriovenous access surgery.
AB  - BACKGROUND: Although ultrasound-guided supraclavicular block has a good success
      rate, it remains unclear whether multiple injections are superior to single
      injection (SI). We compared the sensory block success rate of SI versus triple
      injection (TI). METHODS: In this randomized double-blind study, 96 end-stage
      renal disease patients undergoing arteriovenous fistula creation or
      superficialization were randomly allocated to receive either SI or TI. The
      primary outcome was the combined score of sensory blockade of the 5 nerves
      (median, ulnar, radial, medial cutaneous nerve of the forearm, and
      musculocutaneous) measured at 5, 10, 15, and 20 minutes after injection.
      Secondary outcome variables were the time to onset of the blockade, performance
      time (time to do the block), separate success rate for each of the above nerves,
      success rate of surgical anesthesia, and the complication rate. RESULTS: The
      combined success of the sensory block was 20% to 31% higher in the TI group than
      in the SI group at 10, 15, and 20 minutes after injection (all P < 0.035). The
      block of the musculocutaneous nerve in the TI group was faster and more
      successful than in the SI group, at all time points (all P < 0.026). The average
      time needed to perform the block was significantly longer in the TI than the SI
      group (6.5 +/- 2.1 vs 4.7 +/- 2.1 minutes, P = 0.001). The overall success of
      surgical anesthesia measured at 30 minutes did not differ significantly between
      the 2 groups (96% in TI vs 87% in SI, P = 0.253). CONCLUSIONS: Although the
      performance time of the SI technique was shorter, TI had a faster onset and
      resulted in a more successful block of all nerves in the first 20 minutes.

PMID- 24686047
TI  - Montelukast attenuates neuropathic pain through inhibiting p38 mitogen-activated
      protein kinase and nuclear factor-kappa B in a rat model of chronic constriction
      injury.
AB  - BACKGROUND: Cysteinyl leukotrienes and their receptors have been shown to be
      involved in the generation of neuropathic pain. We performed this study to
      determine the antagonistic effect of montelukast, a cysteinyl leukotrienes
      receptor antagonist, on neuropathic pain and its underlying mechanism. METHODS:
      Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic
      nerve in rats. After CCI, rats were repeatedly administered montelukast (0.5,
      1.0, and 2.0 mg/kg intraperitoneal, once daily) for a period of 14 days.
      Mechanical withdrawal threshold and thermal withdrawal latency were assessed
      before surgery and on days 1, 3, 5, 7, and 14 after CCI. The levels of
      interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in the spinal
      cord were determined by enzyme-linked immunosorbent assay. The phosphorylation of
      p38 mitogen-activated protein kinase (MAPK) and activation of nuclear factor
      kappaB (NF-kappaB) were assessed by Western blot. The expression of astrocyte
      marker glial fibrillary acidic protein and microglia marker Iba-1 and the
      coexpression of p-p38MAPK and Iba-1 or NF-kappaB and Iba-1 were observed by
      immunofluorescent staining. RESULTS: The CCI group displayed significantly
      decreased mechanical withdrawal threshold and thermal withdrawal latency on days
      1, 3, 5, 7 and 14 compared with sham groups (P <0.05, P < 0.0001), which were
      markedly increased by montelukast (P < 0.05, P < 0.01, P <0.0001). After
      administration with montelukast for 14 days, as biological markers of
      inflammation, the levels of IL-1beta (P < 0.0001), IL-6 (P = 0.001 for low
      dosage, P < 0.0001 for middle and high dosages), and TNF-alpha (P =0.002, 0.001,
      < 0.0001 for low, middle, and high dosage, respectively) in the spinal cord were
      lower than those in the CCI group. Western blot analysis demonstrated that
      montelukast reduced the elevated expression of p-p38 MAPK (P =0.006, 0.015, <
      0.0001 for low, middle, and high dosage, respectively) and NF-kappaB (P < 0.0001)
      in the spinal cord induced by CCI. Immunofluorescent staining showed that
      montelukast could inhibit CCI-induced activation of microglia but not astrocytes
      in the spinal cord. In addition, montelukast (2.0 mg/kg) significantly decreased
      the number of p38MAPK and Iba-1 or NF-kappaBp65 and Iba-1 double-positive cells.
      CONCLUSIONS: These results suggest that montelukast could effectively attenuate
      neuropathic pain in CCI rats by inhibiting the activation of p38MAPK and NF
      kappaB signaling pathways in spinal microglia.

PMID- 24686048
TI  - Integration of magnetoencephalography-generated functional brain maps into dose
      planning during arteriovenous malformation radiosurgery.
AB  - BACKGROUND: Magnetoencephalography (MEG) can delineate critical regions of the
      cortex and facilitate conformal stereotactic radiosurgery (SRS) dose planning.
      Despite the substantial role of Gamma Knife(r) SRS in arteriovenous malformation
      (AVM) management, MEG-generated maps of critical regions have never been utilized
      to improve dose planning. PURPOSE: To assess the value of integrating functional
      brain mapping using MEG with dose planning during treatment of brain AVMs with
      SRS. METHODS: This case series encompassed 5 patients with motor region AVMs.
      Noninvasive eloquent cortex mapping was achieved using a whole-head 306-channel
      Neuromag(r) Vectorview MEG System 5-10 days before SRS. On the day of SRS, the
      functional brain maps were integrated onto the intraoperative dose planning
      magnetic resonance imaging for Leksell GammaPlan(r) version 10. The median AVM
      volume treated was 12.7 cm(3), and 18 Gy was the median margin dose. RESULTS:
      Functional image integration of MEG improved the recognition of critical brain
      structures adjacent to the AVM. This facilitated anatomical planning designed to
      reduce the dose to adjacent critical structures while maintaining a therapeutic
      dose to the AVM target. The 5 patients had no adverse radiation effects during
      the follow-up. CONCLUSION: Coregistration of MEG data improves the accuracy and
      dose sparing needed for optimal planning during Gamma Knife SRS.

PMID- 24686049
TI  - Applying a knowledge translation model to the uptake of the Baby Friendly Health
      Initiative in the Australian health care system.
AB  - BACKGROUND: The Baby Friendly Hospital Initiative is a global, evidence-based,
      public health initiative. The evidence underpinning the Initiative supports
      practices promoting the initiation and maintenance of breastfeeding and
      encourages women's informed infant feeding decisions. In Australia, where the
      Initiative is known as the Baby Friendly Health Initiative (BFHI) the translation
      of evidence into practice has not been uniform, as demonstrated by a varying
      number of maternity facilities in each State and Territory currently accredited
      as 'baby friendly'. This variance has persisted regardless of BFHI implementation
      in Australia gaining 'in principle' support at a national and governmental level
      as well as inclusion in health policy in several states. There are many
      stakeholders that exert an influence on policy development and health care
      practices. AIM: Identify a theory and model to examine where and how barriers
      occur in the gap between evidence and practice in the uptake of the BFHI in
      Australia. RESULTS: Knowledge translation theory and the research to practice
      pipeline model are used to examine the identified barriers to BFHI implementation
      and accreditation in Australia. CONCLUSION: Australian and international studies
      have identified similar issues that have either enabled implementation of the
      BFHI or acted as a barrier. Knowledge translation theory and the research to
      practice pipeline model is of practical value to examine barriers.
      Recommendations in the form of specific targeted strategies to facilitate
      knowledge transfer and supportive practices into the Australian health care
      system and current midwifery practice are included.

PMID- 24686050
TI  - New insights into the role of chronic inflammation and cytokines in the
      etiopathogenesis of gastroenteropancreatic neuroendocrine tumors.
AB  - Although previously considered rare, recent epidemiological studies have revealed
      that the incidence (3.6/100,000) and prevalence (35/100,000) of
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased over the
      past few decades. Despite the progress in the understanding of GEP-NET molecular
      biology, there is still little advance in the early diagnosis due to lack of
      specific tumor markers. As the tumors are mostly detected in their late stage,
      they are not well controlled by either biotherapy or conventional chemotherapy,
      and thus represent a significant clinical issue. Chronic inflammation has been
      implicated in the development of GEP-NETs. This review presents recent findings
      that link pro-inflammatory cytokines to the molecular basis of GEP-NET
      tumorigenesis, leading to a more personalized approach to disease management and
      therapy.

PMID- 24686051
TI  - Clinical characteristics and phenotype-genotype analysis in Turkish patients with
      congenital hyperinsulinism; predominance of recessive KATP channel mutations.
AB  - OBJECTIVE: Congenital hyperinsulinism (CHI) is the commonest cause of
      hyperinsulinaemic hypoglycaemia in the neonatal, infancy and childhood periods.
      Its clinical presentation, histology and underlying molecular biology are
      extremely heterogeneous. The aim of this study was to describe the clinical
      characteristics, analyse the genotype-phenotype correlations and describe the
      treatment outcome of Turkish CHI patients. DESIGN AND METHODS: A total of 35
      patients with CHI were retrospectively recruited from four large paediatric
      endocrine centres in Turkey. Detailed clinical, biochemical and genotype
      information was collected. RESULTS: Diazoxide unresponsiveness was observed in
      nearly half of the patients (n=17; 48.5%). Among diazoxide-unresponsive patients,
      mutations in ABCC8/KCNJ11 were identified in 16 (94%) patients. Among diazoxide
      responsive patients (n=18), mutations were identified in two patients (11%).
      Genotype-phenotype correlation revealed that mutations in ABCC8/KCNJ11 were
      associated with an increased birth weight and early age of presentation. Five
      patients had p.L1171fs (c.3512del) ABCC8 mutations, suggestive of a founder
      effect. The rate of detection of a pathogenic mutation was higher in
      consanguineous families compared with non-consanguineous families (87.5 vs 21%;
      P<0.0001).Among the diazoxide-unresponsive group, ten patients were medically
      managed with octreotide therapy and carbohydrate-rich feeds and six patients
      underwent subtotal pancreatectomy. There was a high incidence of developmental
      delay and cerebral palsy among diazoxide-unresponsive patients. CONCLUSIONS: This
      is the largest study to report genotype-phenotype correlations among Turkish
      patients with CHI. Mutations in ABCC8 and KCNJ11 are the commonest causes of CHI
      in Turkish patients (48.6%). There is a higher likelihood of genetic diagnosis in
      patients with early age of presentation, higher birth weight and from
      consanguineous pedigrees.

PMID- 24686053
TI  - Identification of early interactions between Francisella and the host.
AB  - The adaptive immune response to Francisella tularensis is dependent on the route
      of inoculation. Intradermal inoculation with the F. tularensis live vaccine
      strain (LVS) results in a robust Th1 response in the lungs, whereas intranasal
      inoculation produces fewer Th1 cells and instead many Th17 cells. Interestingly,
      bacterial loads in the lungs are similar early after inoculation by these two
      routes. We hypothesize that the adaptive immune response is influenced by local
      events in the lungs, such as the type of cells that are first infected with
      Francisella. Using fluorescence-activated cell sorting, we identified alveolar
      macrophages as the first cell type infected in the lungs of mice intranasally
      inoculated with F. novicida U112, LVS, or F. tularensis Schu S4. Following
      bacterial dissemination from the skin to the lung, interstitial macrophages or
      neutrophils are infected. Overall, we identified the early interactions between
      Francisella and the host following two different routes of inoculation. 

PMID- 24686052
TI  - Inhibition of the alternative pathway of nonhuman infant complement by porin B2
      contributes to virulence of Neisseria meningitidis in the infant rat model.
AB  - Neisseria meningitidis utilizes capsular polysaccharide, lipooligosaccharide
      (LOS) sialic acid, factor H binding protein (fHbp), and neisserial surface
      protein A (NspA) to regulate the alternative pathway (AP) of complement. Using
      meningococcal mutants that lacked all four of the above-mentioned molecules
      (quadruple mutants), we recently identified a role for PorB2 in attenuating the
      human AP; inhibition was mediated by human fH, a key downregulatory protein of
      the AP. Previous studies showed that fH downregulation of the AP via fHbp or NspA
      is specific for human fH. Here, we report that PorB2-expressing quadruple mutants
      also regulate the AP of baby rabbit and infant rat complement. Blocking a human
      fH binding region on PorB2 of the quadruple mutant of strain 4243 with a chimeric
      protein that comprised human fH domains 6 and 7 fused to murine IgG Fc enhanced
      AP-mediated baby rabbit C3 deposition, which provided evidence for an fH
      dependent mechanism of nonhuman AP regulation by PorB2. Using isogenic mutants of
      strain H44/76 that differed only in their PorB molecules, we confirmed a role for
      PorB2 in resistance to killing by infant rat serum. The PorB2-expressing strain
      also caused higher levels of bacteremia in infant rats than its isogenic PorB3
      expressing counterpart, thus providing a molecular basis for increased survival
      of PorB2 isolates in this model. These studies link PorB2 expression with
      infection of infant rats, which could inform the choice of meningococcal strains
      for use in animal models, and reveals, for the first time, that PorB2-expressing
      strains of N. meningitidis regulate the AP of baby rabbits and rats. 

PMID- 24686054
TI  - Vitamin d deficiency reduces the immune response, phagocytosis rate, and
      intracellular killing rate of microglial cells.
AB  - Meningitis and meningoencephalitis caused by Escherichia coli are associated with
      high rates of mortality and neurological sequelae. A high prevalence of
      neurological disorders has been observed in geriatric populations at risk of
      hypovitaminosis D. Vitamin D has potent effects on human immunity, including
      induction of antimicrobial peptides (AMPs) and suppression of T-cell
      proliferation, but its influence on microglial cells is unknown. The purpose of
      the present study was to determine the effects of vitamin D deficiency on the
      phagocytosis rate, intracellular killing, and immune response of murine
      microglial cultures after stimulation with the Toll-like receptor (TLR) agonists
      tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I.C) (TLR3), lipopolysaccharide
      (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high
      concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF
      alpha) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to
      that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1
      after stimulation of microglial cells with high concentrations of TLR3, -4, and 
      9 agonists and intracellular killing of E. coli K1 after stimulation with high
      concentrations of all TLR agonists were lower in vitamin D-deficient microglial
      cells than in the respective control cells. Our observations suggest that vitamin
      D deficiency may impair the resistance of the brain against bacterial infections.

PMID- 24686055
TI  - Vaccination with a single CD4 T cell peptide epitope from a Salmonella type III
      secreted effector protein provides protection against lethal infection.
AB  - Salmonella infections affect millions worldwide and remain a significant cause of
      morbidity and mortality. It is known from mouse studies that CD4 T cells are
      essential mediators of immunity against Salmonella infection, yet it is not clear
      whether targeting CD4 T cell responses directly with peptide vaccines against
      Salmonella can be effective in combating infection. Additionally, it is not known
      whether T cell responses elicited against Salmonella secreted effector proteins
      can provide protective immunity against infection. In this study, we investigated
      both of these possibilities using prime-boost immunization of susceptible mice
      with a single CD4 T cell peptide epitope from Salmonella secreted effector
      protein I (SseI), a component of the Salmonella type III secretion system. This
      immunization conferred significant protection against lethal oral infection,
      equivalent to that conferred by whole heat-killed Salmonella bacteria.
      Surprisingly, a well-characterized T cell epitope from the flagellar protein FliC
      afforded no protection compared to immunization with an irrelevant control
      peptide. The protective response appeared to be most associated with
      polyfunctional CD4 T cells raised against the SseI peptide, since no antibodies
      were produced against any of the peptides and very little CD8 T cell response was
      observed. Overall, this study demonstrates that eliciting CD4 T cell responses
      against components of the Salmonella type III secretion system can contribute to
      protection against infection and should be considered in the design of future
      Salmonella subunit vaccines. 

PMID- 24686056
TI  - ALOX12 in human toxoplasmosis.
AB  - ALOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a
      nonheme lipoxygenase family of dioxygenases. ALOX12 catalyzes the addition of
      oxygen to arachidonic acid, producing 12-hydroperoxyeicosatetraenoic acid (12
      HPETE), which can be reduced to the eicosanoid 12-HETE (12
      hydroxyeicosatetraenoic acid). 12-HETE acts in diverse cellular processes,
      including catecholamine synthesis, vasoconstriction, neuronal function, and
      inflammation. Consistent with effects on these fundamental mechanisms, allelic
      variants of ALOX12 are associated with diseases including schizophrenia,
      atherosclerosis, and cancers, but the mechanisms have not been defined.
      Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality
      and stimulates an innate and adaptive immune inflammatory reaction. Recently, it
      has been shown that a gene region known as Toxo1 is critical for susceptibility
      or resistance to T. gondii infection in rats. An orthologous gene region with
      ALOX12 centromeric is also present in humans. Here we report that the human
      ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis
      (rs6502997 [P, <0.000309], rs312462 [P, <0.028499], rs6502998 [P, <0.029794], and
      rs434473 [P, <0.038516]). A human monocytic cell line was genetically engineered
      using lentivirus RNA interference to knock down ALOX12. In ALOX12 knockdown
      cells, ALOX12 RNA expression decreased and levels of the ALOX12 substrate,
      arachidonic acid, increased. ALOX12 knockdown attenuated the progression of T.
      gondii infection and resulted in greater parasite burdens but decreased
      consequent late cell death of the human monocytic cell line. These findings
      suggest that ALOX12 influences host responses to T. gondii infection in human
      cells. ALOX12 has been shown in other studies to be important in numerous
      diseases. Here we demonstrate the critical role ALOX12 plays in T. gondii
      infection in humans. 

PMID- 24686057
TI  - IsdC from Staphylococcus lugdunensis induces biofilm formation under low-iron
      growth conditions.
AB  - Staphylococcus lugdunensis is a coagulase-negative staphylococcus that is a
      commensal of humans and an opportunistic pathogen. It can cause a spectrum of
      infections, including those that are associated with the ability to form biofilm,
      such as occurs with endocarditis or indwelling medical devices. The genome
      sequences of two strains revealed the presence of orthologues of the ica genes
      that are responsible for synthesis of poly-N-acetylglucosamine (PNAG) that is
      commonly associated with biofilm in other staphylococci. However, we discovered
      that biofilm formed by a panel of S. lugdunensis isolates growing in iron
      restricted medium was susceptible to degradation by proteases and not by
      metaperiodate, suggesting that the biofilm matrix comprised proteins and not
      PNAG. When the iron concentration was raised to 1 mM biofilm formation by all
      strains tested was greatly reduced. A mutant of strain N920143 lacking the entire
      locus that encodes iron-regulated surface determinant (Isd) proteins was
      defective in biofilm formation under iron-limited conditions. An IsdC-null mutant
      was defective, whereas IsdK, IsdJ, and IsdB mutants formed biofilm to the same
      level as the parental strain. Expression of IsdC was required both for the
      primary attachment to unconditioned polystyrene and for the accumulation phase of
      biofilm involving cell-cell interactions. Purified recombinant IsdC protein
      formed dimers in solution and Lactococcus lactis cells expressing only IsdC
      adhered to immobilized recombinant IsdC but not to IsdJ, IsdK, or IsdB. This is
      consistent with a specific homophilic interaction between IsdC molecules on
      neighboring cells contributing to accumulation of S. lugdunensis biofilm in vivo.

PMID- 24686058
TI  - Phase variation mediates reductions in expression of surface proteins during
      persistent meningococcal carriage.
AB  - Asymptomatic and persistent colonization of the upper respiratory tract by
      Neisseria meningitidis occurs despite elicitation of adaptive immune responses
      against surface antigens. A putative mechanism for facilitating host persistence
      of this bacterial commensal and pathogen is alterations in expression of surface
      antigens by simple sequence repeat (SSR)-mediated phase variation. We
      investigated how often phase variation occurs during persistent carriage by
      analyzing the SSRs of eight loci in multiple isolates from 21 carriers
      representative of 1 to 6 months carriage. Alterations in repeat number were
      detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of
      carriage. The expression states were determined by Western blotting and two
      genes, fetA and nadA, exhibited trends toward low expression states. A critical
      finding from our unique examination of combinatorial expression states,
      "phasotypes," was for significant reductions in expression of multiple phase
      variable surface proteins during persistent carriage of some strains. The immune
      responses in these carriers were examined by measuring variant-specific PorA IgG
      antibodies, capsular group Y IgG antibodies and serum bactericidal activity in
      concomitant serum samples. Persistent carriage was associated with high levels of
      specific IgG antibodies and serum bactericidal activity while recent strain
      acquisition correlated with a significant induction of antibodies. We conclude
      that phase-variable genes are driven into lower expression states during long
      term persistent meningococcal carriage, in part due to continuous exposure to
      antibody-mediated selection, suggesting localized hypermutation has evolved to
      facilitate host persistence. 

PMID- 24686059
TI  - Fibronectin-binding protein of Borrelia hermsii expressed in the blood of mice
      with relapsing fever.
AB  - To identify and characterize surface proteins expressed by the relapsing fever
      (RF) agent Borrelia hermsii in the blood of infected mice, we used a cell-free
      filtrate of their blood to immunize congenic naive mice. The resultant antiserum
      was used for Western blotting of cell lysates, and gel slices corresponding to
      reactive bands were subjected to liquid chromatography-tandem mass spectrometry,
      followed by a search of the proteome database with the peptides. One of the
      immunogens was identified as the BHA007 protein, which is encoded by a 174-kb
      linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed
      by the criteria of in situ protease susceptibility and agglutination of Vtp(-)
      cells by anti-BHA007 antibodies, and was not essential for in vitro growth.
      BHA007 elicited antibodies during experimental infection of mice, but
      immunization with recombinant protein did not confer protection against needle
      delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found
      on large plasmids of other RF species, including the coding sequences for the
      CihC proteins of Borrelia duttonii and B. recurrentis, but not in Lyme disease
      Borrelia species. Recombinant BHA007 bound both human and bovine fibronectin with
      Kd (dissociation constant) values of 22 and 33 nM, respectively, and bound to C4
      binding protein with less affinity. The distant homology of BHA007 and its
      orthologs to BBK32 proteins of Lyme disease species, as well as to previously
      described BBK32-like proteins in relapsing fever species, indicates that BHA007
      is a member of a large family of multifunctional proteins in Borrelia species
      that bind to fibronectin as well as other host proteins. 

PMID- 24686060
TI  - Role of capsule and suilysin in mucosal infection of complement-deficient mice
      with Streptococcus suis.
AB  - Virulent Streptococcus suis serotype 2 strains are invasive extracellular
      bacteria causing septicemia and meningitis in piglets and humans. One objective
      of this study was to elucidate the function of complement in innate immune
      defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-)
      mice demonstrated for the first time that the complement system protects naive
      mice against invasive mucosal S. suis infection. S. suis WT but not an
      unencapsulated mutant caused mortality associated with meningitis and other
      pathologies in C3(-/-) mice. The capsule contributed also substantially to
      colonization of the upper respiratory tract. Experimental infection of C3(-/-)
      mice with a suilysin mutant indicated that suilysin expression facilitated an
      early disease onset and the pathogenesis of meningitis. Flow cytometric analysis
      revealed C3 antigen deposition on the surface of ca. 40% of S. suis WT bacteria
      after opsonization with naive WT mouse serum, although to a significantly lower
      intensity than on the unencapsulated mutant. Ex vivo multiplication in murine WT
      and C3(-/-) blood depended on capsule but not suilysin expression. Interestingly,
      S. suis invasion of inner organs was also detectable in C5aR(-/-) mice,
      suggesting that chemotaxis and activation of immune cells via the anaphylatoxin
      receptor C5aR is, in addition to opsonization, a further important function of
      the complement system in defense against mucosal S. suis infection. In
      conclusion, we unequivocally demonstrate here the importance of complement
      against mucosal S. suis serotype 2 infection and that the capsule of this
      pathogen is also involved in escape from complement-independent immunity. 

PMID- 24686061
TI  - Citrullination and proteolytic processing of chemokines by Porphyromonas
      gingivalis.
AB  - The outgrowth of Porphyromonas gingivalis within the inflammatory subgingival
      plaque is associated with periodontitis characterized by periodontal tissue
      destruction, loss of alveolar bone, periodontal pocket formation, and eventually,
      tooth loss. Potential virulence factors of P. gingivalis are peptidylarginine
      deiminase (PPAD), an enzyme modifying free or peptide-bound arginine to
      citrulline, and the bacterial proteases referred to as gingipains (Rgp and Kgp).
      Chemokines attract leukocytes during inflammation. However, posttranslational
      modification (PTM) of chemokines by proteases or human peptidylarginine
      deiminases may alter their biological activities. Since chemokine processing may
      be important in microbial defense mechanisms, we investigated whether PTM of
      chemokines by P. gingivalis enzymes occurs. Upon incubation of interleukin-8 (IL
      8; CXCL8) with PPAD, only minor enzymatic citrullination was detected. In
      contrast, Rgp rapidly cleaved CXCL8 in vitro. Subsequently, different P.
      gingivalis strains were incubated with the chemokine CXCL8 or CXCL10 and their
      PTMs were investigated. No significant CXCL8 citrullination was detected for the
      tested strains. Interestingly, although considerable differences in the
      efficiency of CXCL8 degradation were observed with full cultures of various
      strains, similar rates of chemokine proteolysis were exerted by cell-free culture
      supernatants. Sequencing of CXCL8 incubated with supernatant or bacteria showed
      that CXCL8 is processed into its more potent forms consisting of amino acids 6 to
      77 and amino acids 9 to 77 (the 6-77 and 9-77 forms, respectively). In contrast,
      CXCL10 was entirely and rapidly degraded by P. gingivalis, with no transient
      chemokine forms being observed. In conclusion, this study demonstrates PTM of
      CXCL8 and CXCL10 by gingipains of P. gingivalis and that strain differences may
      particularly affect the activity of these bacterial membrane-associated
      proteases. 

PMID- 24686063
TI  - A putative regulatory genetic locus modulates virulence in the pathogen
      Leptospira interrogans.
AB  - Limited research has been conducted on the role of transcriptional regulators in
      relation to virulence in Leptospira interrogans, the etiological agent of
      leptospirosis. Here, we identify an L. interrogans locus that encodes a sensor
      protein, an anti-sigma factor antagonist, and two genes encoding proteins of
      unknown function. Transposon insertion into the gene encoding the sensor protein
      led to dampened transcription of the other 3 genes in this locus. This lb139
      insertion mutant (the lb139(-) mutant) displayed attenuated virulence in the
      hamster model of infection and reduced motility in vitro. Whole-transcriptome
      analyses using RNA sequencing revealed the downregulation of 115 genes and the
      upregulation of 28 genes, with an overrepresentation of gene products functioning
      in motility and signal transduction and numerous gene products with unknown
      functions, predicted to be localized to the extracellular space. Another
      significant finding encompassed suppressed expression of the majority of the
      genes previously demonstrated to be upregulated at physiological osmolarity,
      including the sphingomyelinase C precursor Sph2 and LigB. We provide insight into
      a possible requirement for transcriptional regulation as it relates to
      leptospiral virulence and suggest various biological processes that are affected
      due to the loss of native expression of this genetic locus. 

PMID- 24686062
TI  - Vibrio cholerae-induced inflammation in the neonatal mouse cholera model.
AB  - Vibrio cholerae is the causative agent of the acute diarrheal disease of cholera.
      Innate immune responses to V. cholerae are not a major cause of cholera
      pathology, which is characterized by severe, watery diarrhea induced by the
      action of cholera toxin. Innate responses may, however, contribute to resolution
      of infection and must be required to initiate adaptive responses after natural
      infection and oral vaccination. Here we investigated whether a well-established
      infant mouse model of cholera can be used to observe an innate immune response.
      We also used a vaccination model in which immunized dams protect their pups from
      infection through breast milk antibodies to investigate innate immune responses
      after V. cholerae infection for pups suckled by an immune dam. At the peak of
      infection, we observed neutrophil recruitment accompanied by induction of KC,
      macrophage inflammatory protein 2 (MIP-2), NOS-2, interleukin-6 (IL-6), and IL
      17a. Pups suckled by an immunized dam did not mount this response. Accessory
      toxins RtxA and HlyA played no discernible role in neutrophil recruitment in a
      wild-type background. The innate response to V. cholerae deleted for cholera
      toxin-encoding phage (CTX) and part of rtxA was significantly reduced, suggesting
      a role for CTX-carried genes or for RtxA in the absence of cholera toxin (CTX).
      Two extracellular V. cholerae DNases were not required for neutrophil
      recruitment, but DNase-deficient V. cholerae caused more clouds of DNA in the
      intestinal lumen, which appeared to be neutrophil extracellular traps (NETs),
      suggesting that V. cholerae DNases combat NETs. Thus, the infant mouse model has
      hitherto unrecognized utility for interrogating innate responses to V. cholerae
      infection. 

PMID- 24686064
TI  - Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes
      attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague.
AB  - Currently, there is no FDA-approved vaccine against Yersinia pestis, the
      causative agent of bubonic and pneumonic plague. Since both humoral immunity and
      cell-mediated immunity are essential in providing the host with protection
      against plague, we developed a live-attenuated vaccine strain by deleting the
      Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y.
      pestis CO92. The Deltalpp Deltapla double isogenic mutant was highly attenuated
      in evoking both bubonic and pneumonic plague in a mouse model. Further, animals
      immunized with the mutant by either the intranasal or the subcutaneous route were
      significantly protected from developing subsequent pneumonic plague. In mice, the
      mutant poorly disseminated to peripheral organs and the production of
      proinflammatory cytokines concurrently decreased. Histopathologically, reduced
      damage to the lungs and livers of mice infected with the Deltalpp Deltapla double
      mutant compared to the level of damage in wild-type (WT) CO92-challenged animals
      was observed. The Deltalpp Deltapla mutant-immunized mice elicited a humoral
      immune response to the WT bacterium, as well as to CO92-specific antigens.
      Moreover, T cells from mutant-immunized animals exhibited significantly higher
      proliferative responses, when stimulated ex vivo with heat-killed WT CO92
      antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise,
      T cells from the mutant-immunized mice produced more gamma interferon (IFN-gamma)
      and interleukin-4. These animals had an increasing number of tumor necrosis
      factor alpha (TNF-alpha)-producing CD4(+) and CD8(+) T cells than WT CO92
      infected mice. These data emphasize the role of TNF-alpha and IFN-gamma in
      protecting mice against pneumonic plague. Overall, our studies provide evidence
      that deletion of the lpp and pla genes acts synergistically in protecting animals
      against pneumonic plague, and we have demonstrated an immunological basis for
      this protection. 

PMID- 24686065
TI  - In vivo splenic clearance correlates with in vitro deformability of red blood
      cells from Plasmodium yoelii-infected mice.
AB  - Recent experimental and clinical studies suggest a crucial role of mechanical
      splenic filtration in the host's defense against malaria parasites. Subtle
      changes in red blood cell (RBC) deformability, caused by infection or drug
      treatment, could influence the pathophysiological outcome. However, in vitro
      deformability measurements have not been directly linked in vivo with the splenic
      clearance of RBCs. In this study, mice infected with malaria-inducing Plasmodium
      yoelii revealed that chloroquine treatment could lead to significant alterations
      to RBC deformability and increase clearance of both infected and uninfected RBCs
      in vivo. These results have clear implications for the mechanism of human
      malarial anemia, a severe pathological condition affecting malaria patients. 

PMID- 24686066
TI  - Novel pneumocystis antigen discovery using fungal surface proteomics.
AB  - Pneumonia due to the fungus Pneumocystis jirovecii is a life-threatening
      infection that occurs in immunocompromised patients. The inability to culture the
      organism as well as the lack of an annotated genome has hindered antigen
      discovery that could be useful in developing novel vaccine- or antibody-based
      therapies as well as diagnostics for this infection. Here we report a novel
      method of surface proteomics analysis of Pneumocystis murina that reliably
      detected putative surface proteins that are conserved in Pneumocystis jirovecii.
      This technique identified novel CD4(+) T-cell epitopes as well as a novel B-cell
      epitope, Meu10, which encodes a glycosylphosphatidylinositol (GPI)-anchored
      protein thought to be involved in ascospore assembly. The described technique
      should facilitate the discovery of novel target proteins for diagnostics and
      therapeutics for Pneumocystis infection. 

PMID- 24686067
TI  - The tick salivary protein sialostatin L2 inhibits caspase-1-mediated inflammation
      during Anaplasma phagocytophilum infection.
AB  - Saliva from arthropod vectors facilitates blood feeding by altering host
      inflammation. Whether arthropod saliva counters inflammasome signaling, a protein
      scaffold that regulates the activity of caspase-1 and cleavage of interleukin
      1beta (IL-1beta) and IL-18 into mature molecules, remains elusive. In this study,
      we provide evidence that a tick salivary protein, sialostatin L2, inhibits
      inflammasome formation during pathogen infection. We show that sialostatin L2
      targets caspase-1 activity during host stimulation with the rickettsial agent
      Anaplasma phagocytophilum. A. phagocytophilum causes macrophage activation and
      hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was
      not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear
      factor kappaB or cathepsin L signaling. Reactive oxygen species from NADPH
      oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory
      process. Altogether, our data expand the knowledge of immunoregulatory pathways
      of tick salivary proteins and unveil an important finding in inflammasome
      biology. 

PMID- 24686068
TI  - Functional antibodies against VAR2CSA in nonpregnant populations from colombia
      exposed to Plasmodium falciparum and Plasmodium vivax.
AB  - In pregnancy, parity-dependent immunity is observed in response to placental
      infection with Plasmodium falciparum. Antibodies recognize the surface antigen,
      VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the
      placental tissue. In most settings of malaria endemicity, antibodies against
      VAR2CSA are predominantly observed in multigravid women and infrequently in men,
      children, and nulligravid women. However, in Colombia, we detected antibodies
      against multiple constructs of VAR2CSA among men and children with acute P.
      falciparum and Plasmodium vivax infection. The majority of men and children
      (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA:
      DBL5epsilon, DBL3X, and ID1-ID2. Surprisingly, these antibodies were observed
      only in pregnant women, men, and children exposed either to P. falciparum or to
      P. vivax. Moreover, the anti-VAR2CSA antibodies are of high avidity and
      efficiently inhibit adherence of infected red blood cells to chondroitin sulfate
      A in vitro, suggesting that they are specific and functional. These unexpected
      results suggest that there may be genotypic or phenotypic differences in the
      parasites of this region or in the host response to either P. falciparum or P.
      vivax infection outside pregnancy. These findings may hold significant clinical
      relevance to the pathophysiology and outcome of malaria infections in this
      region. 

PMID- 24686069
TI  - Phosphoethanolamine decoration of Neisseria gonorrhoeae lipid A plays a dual
      immunostimulatory and protective role during experimental genital tract
      infection.
AB  - The induction of an intense inflammatory response by Neisseria gonorrhoeae and
      the persistence of this pathogen in the presence of innate effectors is a
      fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A
      increases gonococcal resistance to complement-mediated bacteriolysis and cationic
      antimicrobial peptides (CAMPs), and recently we reported that wild-type N.
      gonorrhoeae strain FA1090 has a survival advantage relative to a PEA transferase
      A (lptA) mutant in the human urethral-challenge and murine lower genital tract
      infection models. Here we tested the immunostimulatory role of this lipid A
      modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the
      PEA modification and an lptA mutant of strain FA19 induced significantly lower
      levels of NF-kappaB in human embryonic kidney Toll-like receptor 4 (TLR4) cells
      and murine embryonic fibroblasts than wild-type LOS of the parent strain.
      Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in
      female mice infected with the isogenic lptA mutant, in contrast to mice infected
      with the wild-type and complemented lptA mutant bacteria. We also demonstrated
      that lptA mutant bacteria were more susceptible to human and murine cathelicidins
      due to increased binding by these peptides and that the differential induction of
      NF-kappaB by wild-type and unmodified lipid A was more pronounced in the presence
      of CAMPs. This work demonstrates that PEA decoration of lipid A plays both
      protective and immunostimulatory roles and that host-derived CAMPs may further
      reduce the capacity of PEA-deficient lipid A to interact with TLR4 during
      infection. 

PMID- 24686070
TI  - Review of foreign body ingestion and esophageal food impaction management in
      adolescents.
AB  - Foreign body ingestion is a common clinical scenario among patients of all ages.
      The immediate risk to the patient ranges from negligible to life threatening.
      Initial and follow-up management strategies depend on multiple patient and
      ingested object-related factors. Available literature on this topic tends to
      focus on the small child or adult, leaving the clinician caring for adolescents
      to extrapolate this information to guide decision making for individual patients.
      This article reviews foreign body ingestion literature with important
      implications to the adolescent patient and raises awareness of some highly
      dangerous objects such as large button batteries, high-powered magnets, long
      sharps, narcotic packages, and super absorbent objects. An additional focus
      includes the management of esophageal food impaction. We highlight the unique
      aspects to the care of the adolescent with intentional ingestion and co-morbid
      psychiatric illness. The article concludes by discussing the challenges to
      prevention of ingestion in the at-risk patient. 

PMID- 24686072
TI  - Impaired upper alpha synchronisation during working memory retention in
      depression and depression following traumatic brain injury.
AB  - Rates of major depressive disorder (MDD) following traumatic brain injury (TBI)
      are higher than in the general population. Individuals with depression following
      traumatic brain injury (TBI-MDD) exhibit working memory (WM) impairments.
      Electrophysiological evidence has suggested that parieto-occipital upper alpha
      synchronisation may enhance WM retention by inhibiting irrelevant processes. The
      current research assessed whether retention period WM parieto-occipital upper
      alpha activity is disrupted in groups with TBI-only (N=20), MDD (N=17), and TBI
      MDD (N=15) compared to healthy controls (N=31). Behavioural data indicated poorer
      performance in MDD and TBI-MDD. Parietal-occipital upper alpha was reduced in the
      MDD and TBI-MDD groups, but was unaffected in TBI-only. These results suggest
      inhibitory deficits may account for WM impairments in MDD and TBI-MDD, and that
      for individuals with TBI-MDD it may be the depression rather than the TBI that
      impairs WM. 

PMID- 24686071
TI  - Race-related health disparities and biological aging: does rate of telomere
      shortening differ across blacks and whites?
AB  - Recent work suggests that leukocyte telomere length (LTL), a marker of cellular
      aging, is sensitive to effects of social stress and may also provide early
      indication of premature aging. Using data from a birth cohort with LTL
      information at birth and in middle adulthood we examined a potential source of
      race-based health disparity by testing the hypothesis that Blacks would
      demonstrate a faster rate of telomere shortening than Whites. Linear regression
      analyses were conducted and adjusted for pack years, BMI, education and social
      factors, diet, exercise, marital status, and age. At birth black individuals had
      LTLs that were longer, on average, than their White counterparts (b=3.85,
      p<0.01). However, rate of shortening was greater for Blacks, who showed a larger
      difference in length between birth and adulthood (b=5.10, p=0.01) as compared
      with Whites, resulting in smaller racial differences in absolute adult LTL. 

PMID- 24686073
TI  - Effortful control and executive attention in typical and atypical development: an
      event-related potential study.
AB  - Executive attention and its relationship with effortful control (EC) were
      investigated in children with ADHD (n=24), autism spectrum disorder (ASD; n=20),
      and controls (n=21). Executive attention measures included flanker-performance
      and event-related potentials (N2, P3, and ERN). EC was assessed using
      questionnaires. Only the ERN was found to be robustly related to EC across
      groups. N2 did not differ between groups and only children with ADHD+ODD showed
      diminished executive attention as expressed in RT and P3. In ADHD, monitoring of
      incorrect (ERN) and correct (CRN) responses was diminished. Overall, the link
      between EC and executive attention was less strong as expected and varied
      depending on group and measure considered. All groups were able to detect
      conflict (N2) and all but ADHD+ODD were able to allocate extra attention in order
      to respond correctly (P3). Findings indicate a general reduced response
      monitoring in ADHD. 

PMID- 24686074
TI  - Patient perceptions of ultrasound educational scans in the emergency department.
AB  - BACKGROUND: Emergency medicine residents may perform bedside ultrasound (BUS)
      scans that are carried out solely for educational purposes. This may lead to
      confusion on the part of patients, as the implications in the context of their
      medical care may be unclear. STUDY OBJECTIVES: We hypothesized that a scripted
      introduction would improve understanding of the objectives and limitations of
      educational BUS. METHODS: A perceptual survey was completed by a prospectively
      enrolled convenience sample of patients in two emergency departments. In phase 1,
      fifty patients completed the survey after their educational BUS. During phase 2,
      sonographers were provided with a one-paragraph scripted introduction to use and
      50 additional patients were recruited. Group data were analyzed using chi-squared
      tests, Kruskal-Wallis, and t-test. RESULTS: There were no statistical differences
      in demographics between the two groups. The scripted introduction changed several
      survey responses by a statistically significant amount for questions including
      whether their clinician ordered the study, whether it was part of their medical
      care, and whether it would be part of their medical record (p < 0.01). The
      responses as to whether they would tell their doctor that they had an ultrasound
      done were not significantly changed by the script (p = 0.86). CONCLUSION: This
      study demonstrates that the use of a scripted introduction regarding the purpose
      of educational BUS improved patient understanding of the objectives and
      limitations of such scans. There were still areas where the scripted introduction
      did not change patient's perception of the educational BUS scan.

PMID- 24686075
TI  - An unusual cause of right upper quadrant pain and emesis.

PMID- 24686076
TI  - Inverted Meckel's diverticulum.

PMID- 24686077
TI  - Magnetic susceptibility of road deposited sediments at a national scale--relation
      to population size and urban pollution.
AB  - Magnetic properties of road dusts from 26 urban sites in Bulgaria are studied.
      Temporal variations of magnetic susceptibility (chi) during eighteen months
      monitoring account for approximately 1/3rd of the mean annual values. Analysis of
      heavy metal contents and magnetic parameters for the fraction d < 63 MUm reveal
      significant correlations (p < 0.05) between chi and Fe, Mn and PLI index. The
      highest negative correlation (R(2) = -0.84) is observed between the ratio ARM/chi
      and Pb content. It suggests that Pb is related to brake/tyre wear emissions,
      releasing larger particles and higher Pb during slow driving - braking. Bulk chi
      values of road dusts per city show significant correlation with population size
      and mean annual NO2 concentration on a log-normal scale. The results demonstrate
      the applicability of magnetic measurements of road dusts for estimation of mean
      NO2 levels at high spatial density, which is important for pollution modelling
      and health risk assessment. 

PMID- 24686078
TI  - Transplantation of bone marrow mesenchymal stem cells for the treatment of type 2
      diabetes in a macaque model.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are self-renewing, multipotent cells
      that can migrate to pathological sites and thereby provide a new treatment in
      diabetic animals. Superparamagnetic iron oxide/4',6-diamidino-2-phenylindole
      (DAPI) double-labeled BMSCs were transplanted into the pancreatic artery of
      macaques to treat type 2 diabetes mellitus (T2DM). The treatment efficiency of
      BMSCs was also evaluated. After successful induction of the T2DM model, the
      treatment group received double-labeled BMSCs via the pancreatic artery. Six
      weeks after BMSC transplantation, the fasting blood glucose and blood lipid
      levels measured in the treatment group were significantly lower (p < 0.05) than
      in the model group, although they were not reduced to normal levels (p < 0.05).
      Additionally, the serum C-peptide levels were significantly increased (p < 0.05).
      An intravenous glucose tolerance test and C-peptide release test had significant
      changes to the area under the curve. Within 14 days of the transplantation of
      labeled cells, the pancreatic and kidney tissue of the treatment group emitted a
      negative signal that was visible on magnetic resonance imaging (MRI). Six weeks
      after transplantation, DAPI signals appeared in the pancreatic and kidney tissue,
      which indicates that the BMSCs were mainly distributed in damaged tissue. Labeled
      stem cells can be used to track migration and distribution in vivo by MRI. In
      conclusion, the transplantation of BMSCs for the treatment of T2DM is safe and
      effective.

PMID- 24686079
TI  - Heterodimerization of human apelin and bradykinin 1 receptors: novel signal
      transduction characteristics.
AB  - Apelin receptor (APJ) and bradykinin 1 receptor (B1R) are involved in a variety
      of important physiological processes, which share many similar characteristics in
      distribution and functions in the cardiovascular system. This study explored the
      possibility of heterodimerization between APJ and B1R, and investigated the
      impact of heterodimer on the signal transduction characteristics and the
      physiological functions in human endothelial cells after stimulation with their
      agonists. We first identified the endogenous expression of APJ and B1R in HUVECs
      and their co-localization on HEK293 membrane. The constitutive heterodimerization
      between the APJ and B1R was then demonstrated by BRET and FRET assays.
      Stimulation with Apelin-13 and des -Arg(9)-BK enhanced the phosphorylation of
      eNOS in HUVECs, which could be dampened by the knockdown of APJ or B1R,
      indicating the co-existence of APJ and B1R is critical for eNOS phosphorylation
      in HUVECs. Furthermore, APJ/B1R heterodimers were found to enhance the activity
      of PKC signaling pathway and increase intracellular Ca(2+) concentration in
      HEK293 cells, which might be the mechanism of APJ/B1R heterodimers promoting the
      phosphorylation of eNOS and leads to increased Galphaq, PKC signal pathway
      activities and a significant increase in cell proliferation. The results provide
      a new theoretical and experimental base for revealed intracellular molecular
      mechanisms of physiological function involved in the APJ and B1R and provide
      potential new targets for the development of drugs and treating cardiovascular
      disease.

PMID- 24686080
TI  - ER stress signaling in ARPE-19 cells after inhibition of protein kinase CK2 by CX
      4945.
AB  - Protein kinase CK2 is a critical factor for the survival of cells. It is
      overexpressed in many cancer cells and provides protection against apoptosis in
      these cells. Inhibition of CK2 kinase activity in various cancer cells leads to
      apoptosis, which makes CK2 an attractive target for cancer therapy. Little is,
      however, known about CK2 inhibition in non-cancerous cells. Using the human
      retinal pigment epithelial cell line ARPE-19, we analyzed the formation of
      reactive oxygen species (ROS) and the ER stress signaling pathway after CK2
      inhibition with CX-4945. Following CK2 inhibition, we did not find any
      significant generation of ROS in neither ARPE-19 non-cancer cells nor in HCT116
      cancer cells. We found an induction of the ER stress pathway including the
      activation of eIF2alpha and ATF4 in both cell types. This activation was
      sufficient for ARPE-19 cells to cope with the ER stress. Furthermore, in contrast
      to HCT116 cancer cells, there was no induction of the pro-apoptotic transcription
      factor CHOP and no induction of apoptosis in the ARPE-19 cells. Overexpression of
      CHOP, however, induced apoptosis in ARPE-19 cells indicating that this step in
      the ER stress pathway is abrogated in normal cells compared to cancer cell.

PMID- 24686082
TI  - Phosphorylation of heat shock protein 27 antagonizes TNF-alpha induced HeLa cell
      apoptosis via regulating TAK1 ubiquitination and activation of p38 and ERK
      signaling.
AB  - Tumor necrosis factor (TNF)-alpha is a potent cytokine that regulates critical
      cellular processes including apoptosis. TNF-alpha usually triggers both survival
      and apoptotic signals in various cell types. Heat shock protein 27 (HSP27), an
      important cellular chaperone, is believed to protect cells from apoptosis. HSP27
      can be phosphorylated and changed its cellular function according to different
      stimuli. However, available reports on the role of HSP27 phosphorylation in
      apoptosis remain elusive. In this study, we investigated the role of HSP27
      phosphorylation in TNF-alpha induced apoptosis in human cervical carcinoma (HeLa)
      cells. We found that TNF-alpha induced apoptosis was enhanced if we suppressed
      the TNF-alpha induced HSP27 phosphorylation by specific inhibitor CMPD1 or
      MAPKAPK2 (MK2) knockdown or by overexpression of non-phosphorylatable mutant
      HSP27-3A. Through co-immunoprecipitation and confocal microscopy, we observed
      that HSP27 associated with transforming growth factor-beta (TGF-beta)-activated
      kinase 1 (TAK1) in response to TNF-alpha stimulation. By blocking MK2 activity or
      overexpressing phospho-mimetic mutant Hsp27-3D, we further showed that HSP27
      phosphorylation facilitated the TNF-alpha induced ubiquitination and
      phosphorylation of TAK1 and the activations of p38 MAPK and ERK, the TAK1
      downstream pro-survival signaling. In addition, we also found that increased
      HSP27 phosphorylation inhibited TRADD ubiquitination but did not influence the
      binding between TRADD and FADD in a pro-apoptotic complex. Taken together, our
      data indicated that HSP27 phosphorylation was involved in modulating the TNF
      alpha induced apoptosis via interacting with TAK1 and regulating TAK1 post
      translational modifications in HeLa cells. This study demonstrates that HSP27
      phosphorylation serves as a novel regulator in TNF-alpha-induced apoptosis, and
      provides a new insight into the cytoprotective role of HSP27 phosphorylation.

PMID- 24686081
TI  - Mutations in arrestin-3 differentially affect binding to neuropeptide Y receptor
      subtypes.
AB  - Based on the identification of residues that determine receptor selectivity in
      arrestins and the phylogenetic analysis of the arrestin (arr) family, we
      introduced fifteen mutations of receptor-discriminator residues in arr-3, which
      were identified previously using mutagenesis, in vitro binding, and BRET-based
      recruitment assay in intact cells. The effects of these mutations were tested
      using neuropeptide Y receptors Y1R and Y2R. NPY-elicited arr-3 recruitment to Y1R
      was not affected by these mutations, or even alanine substitution of all ten
      residues (arr-3-NCA), which prevented arr-3 binding to other receptors tested so
      far. However, NCA and two other mutations prevented agonist-independent arr-3 pre
      docking to Y1R. In contrast, eight out of 15 mutations significantly reduced
      agonist-dependent arr-3 recruitment to Y2R. NCA eliminated arr-3 binding to
      active Y2R, whereas Tyr239Thr reduced it ~7-fold. Thus, manipulation of key
      residues on the receptor-binding surface generates arr-3 with high preference for
      Y1R over Y2R. Several mutations differentially affect arr-3 pre-docking and
      agonist-induced recruitment. Thus, arr-3 recruitment to the receptor involves
      several mechanistically distinct steps. Targeted mutagenesis can fine-tune
      arrestins directing them to specific receptors and particular activation states
      of the same receptor.

PMID- 24686083
TI  - Using a yeast two-hybrid system to identify FTCD as a new regulator for HIF
      1alpha in HepG2 cells.
AB  - HIF-1alpha is implicated in hepatocellular carcinoma (HCC) pathologies. Here, we
      screened a human liver cDNA library for HIF-1alpha-interacting partners using a
      yeast two-hybrid system. We identified 53 genes, including formiminotransferase
      cyclodeaminase (FTCD), which was confirmed by co-immunoprecipitation. Moreover,
      our data indicated that HIF-1alpha mediated the effects of hypoxia on FTCD
      induction via binding to the hypoxia-responsive elements of the FTCD promoter.
      Knockdown of FTCD reduced the effects of HIF-1alpha in hypoxia and enhanced
      chemosensitivity in HepG2 cells. Our findings suggested crosstalk between FTCD
      and HIF signaling and promoted HCC progression, thus implicating FTCD as a
      therapeutic target for HCC.

PMID- 24686084
TI  - GABARBP down-regulates HIF-1alpha expression through the VEGFR-2 and PI3K/mTOR/4E
      BP1 pathways.
AB  - Human gamma-aminobutyrate type A (GABAA) receptor-binding protein (GABARBP), a
      tumor suppressor protein with apoptotic function, can be inhibited in response to
      angiogenesis through the PI3K/Akt signaling cascades. Here, we investigated
      whether GABARBP over-expression could regulate vascular endothelial growth factor
      (VEGF)/hypoxia-inducible factor-1alpha (HIF-1alpha) expression and angiogenic
      activity in a carcinoma model system. GABARBP dramatically inhibited VEGF-induced
      endothelial cell proliferation, migration, and tube formation, as well as VEGFR-2
      phosphorylation in vitro. At the same time, GABARBP exposed potent anti
      angiogenic activity and remarkably down-regulated the levels of VEGF and HIF
      1alpha protein expression, key components for angiogenesis. In addressing its
      biological molecular mechanism, GABARBP was found to effectively inhibit the
      phosphorylation of down-stream PI3K components, such as PDK1, Akt, mTOR, TSC-2,
      p70S6K, and 4E-BP1 by directly binding with VEGFR-2. In contrast, p38/JNK
      phosphorylation was not suppressed by GABARBP. These findings disclose a novel
      function of GABARBP in suppressing VEGF and HIF-1alpha protein expression, which
      is important for tumor angiogenesis and tumor growth. Thus, our data strongly
      provides novel biological mechanistic insights into the regulatory function of
      GABARBP in ovarian tumor progression, and the important of pre-clinical
      certification of GABARBP as a potential angiogenesis agent targeting ovarian
      tumorigenesis.

PMID- 24686086
TI  - AMPKalpha2 translocates into the nucleus and interacts with hnRNP H: implications
      in metformin-mediated glucose uptake.
AB  - Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cytoplasmic
      protein that plays a critical role in the maintenance of energy homeostasis.
      However, its role in the nucleus is still largely unknown. Here, we showed that
      AMPKalpha2 translocated into the nucleus during muscle differentiation. We also
      showed that upon treatment with 5-aminoimidazole-4-carboxy-amide-1-d
      ribofuranoside (AICAR), an AMPK activator, AMPK rapidly translocated into the
      nucleus in rat myoblast L6 cells. On the other hand, the AMPKalpha2
      phosphorylation-defective mutant did not translocate into the nucleus. Knockdown
      of AMPKalpha2 suppressed the differentiation-induced expression of myogenin, a
      differentiation marker. A physiological AMPK activator, metformin, also induced
      the translocation of AMPKalpha2 into the nucleus. Both inhibition and knockdown
      of AMPKalpha2 suppressed metformin-mediated glucose uptake. In addition,
      AMPKalpha2 was shown to directly interact with the heterogeneous nuclear
      ribonucleoprotein H (hnRNP H). AICAR treatment increased the phosphorylation of
      hnRNP H. Metformin increased the interaction between AMPKalpha2 and hnRNP H in
      the nucleus. Knockdown of hnRNP H blocked metformin-induced glucose uptake. In
      summary, these results demonstrate that AMPKalpha2 translocates into the nucleus
      via phosphorylation, AMPKalpha2 interacts with and phosphorylates hnRNP H in the
      nucleus, and such a protein-protein interaction modulates metformin-mediated
      glucose uptake.

PMID- 24686085
TI  - Phosphorylation of c-Cbl and p85 PI3K driven by all-trans retinoic acid and CD38
      depends on Lyn kinase activity.
AB  - The leukocyte antigen CD38 is expressed after all-trans retinoic acid (ATRA)
      treatment in HL-60 myelogenous leukemia cells and promotes induced myeloid
      differentiation when overexpressed. We found that Vav1 and SLP-76 associate with
      CD38 in two cell lines, and that these proteins complex with Lyn, a Src family
      kinase (SFK) upregulated by ATRA. SFK inhibitors PP2 and dasatinib, which enhance
      ATRA-induced differentiation, were used to evaluate the involvement of Lyn kinase
      activity in CD38-driven signaling. Cells treated with ATRA for 48h followed by
      one hour of PP2 incubation show SFK/Lyn kinase inhibition. We observed that Lyn
      inhibition blocked c-Cbl and p85/p55 PI3K phosphorylation driven by the anti-CD38
      agonistic mAb IB4 in ATRA-treated HL-60 cells and untreated CD38+ transfectants.
      In contrast, cells cultured for 48h following concurrent ATRA and PP2 treatment
      did not show Lyn inhibition, suggesting ATRA regulates the effects on Lyn. 48h of
      co-treatment preserved CD38-stimulated c-Cbl and p85/p55 PI3K phosphorylation
      indicating Lyn kinase activity is necessary for these events. In contrast another
      SFK inhibitor (dasatinib) which blocks Lyn activity with ATRA co-treatment
      prevented ATRA-induced c-Cbl phosphorylation and crippled p85 PI3K
      phosphorylation, indicating Lyn kinase activity is important for ATRA-propelled
      events potentially regulated by CD38. We found that loss of Lyn activity
      coincided with a decrease in Vav1/Lyn/CD38 and SLP-76/Lyn/CD38 interaction,
      suggesting these molecules form a complex that regulates CD38 signaling. Lyn
      inhibition also reduced Lyn and CD38 binding to p85 PI3K, indicating CD38
      facilitates a complex responsible for PI3K phosphorylation. Therefore, Lyn kinase
      activity is important for CD38-associated signaling that may drive ATRA-induced
      differentiation.

PMID- 24686087
TI  - Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of
      STAT3 signalling.
AB  - Understanding the mechanisms of colorectal cancer (CRC) metastatic progression is
      essential to reducing its morbidity and mortality. Pyruvate kinase (PK) catalyses
      the final step of glycolysis and has been identified as a critical regulator of
      glucose consumption. However, the mechanisms and roles of PKM1 and PKM2 in the
      regulation of CRC cell migration and cell adhesion remain elusive. Here, we
      report that PKM2 rather than PKM1 drives CRC cell migration and cell adhesion,
      whereas PKM attenuation reverses these phenomena. Furthermore, the overexpression
      of PKM2 significantly increases the expression of N-cadherin, MMP-2, MMP-9,
      STAT3, Snail-2, pFAK and active beta1-integrin, while E-cadherin expression is
      suppressed. More importantly, the results indicated that PKM2 overexpression
      facilitates STAT3 nuclear translocation, and it is required for PKM2 function in
      the regulation of migration and adhesion associated signalling. In addition, the
      dimeric form of PKM2, which lacks the pyruvate kinase activities but possesses
      protein kinase activity, is critical for CRC cell migration and cell adhesion.
      Overall, this study suggests that PKM2 overexpression promotes CRC cell migration
      and cell adhesion by regulating STAT3-associated signalling and that PKM2 may
      serve as a therapeutic target for CRC metastasis.

PMID- 24686088
TI  - Rlim, an E3 ubiquitin ligase, influences the stability of Stathmin protein in
      human osteosarcoma cells.
AB  - Stathmin is an oncoprotein and is expressed at high levels in a wide variety of
      human malignancies, which plays important roles in maintenance of malignant
      phenotypes. The regulation of Stathmin gene overexpression has been wildly
      explored, but the exact mechanism still needs to be elucidated. It is believed
      that regulation of an oncogene protein abundance through post-translational
      modifications is essential for maintenance of malignant phenotypes. Here we
      identified the Rlim, a Ring H2 zinc finger protein with intrinsic ubiquitin
      ligase activity, as a Stathmin-interacting protein that could increase Stathmin
      turnover through binding with this targeted protein and then induce its
      degradation by proteasome in a ubiquitin-dependent manner. Inhibition of
      endogenous Rlim expression by siRNA could increase the level of Stathmin protein,
      which further led to cell proliferation and cell cycle changes in human
      osteosarcoma cell lines. On the other hand, forced overexpression of Rlim could
      decrease the level of Stathmin protein. These results demonstrate that Rlim is
      involved in the negative regulation of Stathmin protein level through physical
      interaction and ubiquitin-mediated proteolysis. Hence, Rlim is a novel regulator
      of Stathmin protein in a ubiquitin-dependent manner, and represents a new pathway
      for malignant phenotype turnover by modulating the level of Stathmin protein in
      human osteosarcomas.

PMID- 24686090
TI  - Safety and effectiveness of bevacizumab treatment for metastatic colorectal
      cancer: final results from the Avastin((r)) Registry - Investigation of
      Effectiveness and Safety (ARIES) observational cohort study.
AB  - AIMS: The Avastin((r)) Registry - Investigation of Effectiveness and Safety
      (ARIES) observational cohort study (OCS) was designed to prospectively examine
      outcomes associated with bevacizumab-containing treatment for metastatic
      colorectal cancer (mCRC) in a community-based setting, where patient populations
      are less restricted than those in randomised trials. MATERIALS AND METHODS:
      Patients with mCRC who were eligible for bevacizumab in combination with
      chemotherapy in first- or second-line treatment were enrolled from November 2006
      to September 2008. There were no protocol-specified treatment regimens; the dose
      and schedule of bevacizumab and chemotherapy were at the treating physician's
      discretion. The objectives in the ARIES OCS included analyses of progression-free
      survival (PFS), overall survival, treatment patterns and safety in each of the
      first- and second-line treatment cohorts. RESULTS: ARIES enrolled 1550 patients
      with mCRC receiving first-line therapy with bevacizumab. The median follow-up
      time was 20.6 months. The median PFS in this cohort was 10.2 months (95%
      confidence interval 9.8-10.6) and the median overall survival was 23.2 months
      (95% confidence interval 21.2-24.8). In a separate cohort of 482 patients with
      second-line mCRC, the median follow-up time was 16.9 months, the median PFS and
      overall survival from the start of second-line treatment to the end of follow-up
      was 7.9 months (95% confidence interval 7.2-8.3) and 17.8 months (95% confidence
      interval 16.5-20.7), respectively. Incidences of known bevacizumab-associated
      adverse events in ARIES were generally consistent with those previously reported
      in OCSs and randomised trials. CONCLUSION: Results from the prospective ARIES OCS
      add further evidence to support the effectiveness and safety of bevacizumab when
      added to first- and second-line treatment regimens for patients with mCRC in
      community treatment settings.

PMID- 24686091
TI  - Sorption and degradation of petroleum hydrocarbons, polycyclic aromatic
      hydrocarbons, alkylphenols, bisphenol A and phthalates in landfill leachate using
      sand, activated carbon and peat filters.
AB  - Landfill leachates are repeatedly found contaminated with organic pollutants,
      such as alkylphenols (APs), phthalates and polycyclic aromatic hydrocarbons
      (PAHs) at levels exceeding water quality standards. It has been shown that these
      pollutants may be present in the colloidal and truly dissolved phase in
      contaminated water, making particle separation an inefficient removal method. The
      aim of this study was to investigate sorption and degradation of petroleum
      hydrocarbons (PHCs), selected APs, bisphenol A (BPA), phthalates and PAHs from
      landfill leachate using sand, granulated activated carbon (GAC) and peat moss
      filters. A pilot plant was installed at an inactive landfill with mixed
      industrial and household waste and samples were collected before and after each
      filter during two years. Leachate pre-treated in oil separator and sedimentation
      pond failed to meet water quality standards in most samples and little
      improvement was seen after the sand filter. These techniques are based on
      particle removal, whereas the analysed pollutants are found, to varying degrees,
      bound to colloids or dissolved. However, even highly hydrophobic compounds
      expected to be particle-bound, such as the PHCs and high-molecular weight PAHs,
      were poorly removed in the sand filter. The APs and BPA were completely removed
      by the GAC filter, while mass balance calculations indicate that 50-80% of the
      investigated phenols were removed in the peat filter. Results suggest possible AP
      degradation in peat filters. No evidence of phthalate degradation in the
      landfill, pond or the filters was found. The PHCs were completely removed in 50%
      and 35% of the measured occasions in the GAC and peat filters, respectively. The
      opposite trend was seen for removal of PAHs in GAC (50%) and peat (63%).
      Oxygenated PAHs with high toxicity were found in the leachates but not in the
      pond sediment. These compounds are likely formed in the pond water, which is
      alarming because sedimentation ponds are commonly used treatment techniques. The
      oxy-PAHs were effectively removed in the GAC, and especially the peat filter. It
      was hypothesized that dissolved compounds would adsorb equally well to the peat
      and GAC filters. This was not completely supported as the GAC filter was in
      general more efficient than peat. 

PMID- 24686089
TI  - MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age
      of discovery.
AB  - Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS)
      combines the sensitivity and selectivity of mass spectrometry with spatial
      analysis to provide a new dimension for histological analyses to provide unbiased
      visualization of the arrangement of biomolecules in tissue. As such, MALDI IMS
      has the capability to become a powerful new molecular technology for the
      biological and clinical sciences. In this review, we briefly describe several
      applications of MALDI IMS covering a range of molecular weights, from drugs to
      proteins. Current limitations and challenges are discussed along with recent
      developments to address these issues. This article is part of a Special Issue
      entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors:
      Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles
      Sanchez. 

PMID- 24686093
TI  - Support for a history-dependent predictive model of dACC activity in producing
      the bivalency effect: an event-related potential study.
AB  - In the present study, we examine electrophysiological correlates of factors
      influencing an adjustment in cognitive control known as the bivalency effect.
      During task-switching, the occasional presence of bivalent stimuli in a block of
      univalent trials is enough to elicit a response slowing on all subsequent
      univalent trials. Bivalent stimuli can be congruent or incongruent with respect
      to the response afforded by the irrelevant stimulus feature. Here we show that
      the incongruent bivalency effect, the congruent bivalency effect, and an effect
      of a simple violation of expectancy are captured at a frontal ERP component
      (between 300 and 550ms) associated with ACC activity, and that the unexpectedness
      effect is distinguished from both congruent and incongruent bivalency effects at
      an earlier component (100-120ms) associated with the temporal parietal junction.
      We suggest that the frontal component reflects the dACC's role in predicting
      future cognitive load based on recent history. In contrast, the posterior
      component may index early visual feature extraction in response to bivalent
      stimuli that cue currently ongoing tasks; dACC activity may trigger the temporal
      parietal activity only when specific task cueing is involved and not for simple
      violations of expectancy. 

PMID- 24686092
TI  - Neural underpinnings for model-oriented therapy of aphasic word production.
AB  - Model-oriented therapies of aphasic word production have been shown to be
      effective, with item-specific therapy effects being larger than generalisation
      effects for untrained items. However, it remains unclear whether semantic versus
      phonological therapy lead to differential effects, depending on type of lexical
      impairment. Functional imaging studies revealed that mainly left-hemisphere,
      perisylvian brain areas were involved in successful therapy-induced recovery of
      aphasic word production. However, the neural underpinnings for model-oriented
      therapy effects have not received much attention yet. We aimed at identifying
      brain areas indicating (1) general therapy effects using a naming task measured
      by functional magnetic resonance imaging (fMRI) in 14 patients before and after a
      4-week naming therapy, which comprised increasing semantic and phonological
      cueing-hierarchies. We also intended to reveal differential effects (2) of
      training versus generalisation, (3) of therapy methods, and (4) of type of
      impairment as assessed by the connectionist Dell model. Training effects were
      stronger than generalisation effects, even though both were significant.
      Furthermore, significant impairment-specific therapy effects were observed for
      patients with phonological disorders (P-patients). (1) Left inferior frontal
      gyrus, pars opercularis (IFGoper), was a positive predictor of therapy gains
      while the right caudate was a negative predictor. Moreover, less activation
      decrease due to therapy in left-hemisphere temporo-parietal language areas was
      positively correlated with therapy gains. (2) Naming of trained compared to
      untrained words yielded less activation decrease in left superior temporal gyrus
      (STG) and precuneus, bilateral thalamus, and right caudate due to therapy. (3)
      Differential therapy effects could be detected in the right superior parietal
      lobule for the semantic method, and in regions involving bilateral anterior and
      mid cingulate, right precuneus, and left middle/superior frontal gyrus for the
      phonological method. (4) Impairment-specific changes of activation were found for
      P-patients in left IFGoper. Patients with semantic disorders (S-patients) relied
      on right frontal areas involving IFG, pars triangularis. After therapy, they
      revealed less activation decrease in areas involving left STG, caudate,
      paracentral lobule, and right rolandic operculum. Regarding naming performance,
      the present study corroborates previous findings on training and generalisation
      effects and reveals differential therapy effects for P-patients. Moreover, brain
      imaging results confirm a predominance of (1) general effects in the left brain
      hemisphere. (2) Brain regions related to visual strategy, monitoring/feedback,
      and articulatory patterns were characteristic for the familiar trained items. (3)
      Distinct regions associated with strategies, monitoring capacities, and
      linguistic information indicate the specific therapeutic influence on word
      retrieval. (4) While P-patients relied more on preserved phonological functions
      in the left hemisphere, S-patients revealed right-sided compensation of semantic
      processing as well as increased strategic efforts in both hemispheres. 

PMID- 24686094
TI  - The imperfect control of self-reactive germinal center B cells.
AB  - Unlike T cells, B cells diversify their antigen receptor (BCR) binding
      specificities at two distinct stages of differentiation. Thus, in addition to
      initial variable region gene rearrangements, B cells recruited into T-dependent
      immune responses further modify their BCR specificity via iterative rounds of
      somatic hypermutation (SHM) within germinal centers (GCs). Although critical for
      providing the high-affinity antibody specificities required for long-term immune
      protection, SHM can also generate self-reactive B cells capable of
      differentiating into autoantibody-producing plasma cells. Recent data confirm
      that self-reactive GC B cells can be effectively removed from the secondary
      repertoire so as to maintain self-tolerance. However, they can also escape
      deletion under certain circumstances and so contribute to autoimmune disease via
      production of somatically mutated, pathogenic autoantibodies. 

PMID- 24686095
TI  - Nanotechnology in the treatment of inflammatory bowel diseases.
AB  - BACKGROUND AND AIMS: Treatment of inflammatory bowel diseases (IBD) is only aimed
      to block or inhibit the pathogenetic steps of the inflammatory cascade. Side
      effects of systemic therapies, poor targeting of orally administered topical drug
      and low adherence to prescription represent frequent therapeutic challenges.
      Recent observations suggest that nanotechnology could provide amazing advantage
      in this field since particles having dimension in the nanometer scale
      (nanoparticles) can modify pharmacokinetic step of biologic and conventional
      therapeutic agents with a better delivery of drugs within the intestinal
      inflammatory cells. The aim of this review was to provide the clinician with an
      insight into the potential role of nanotechnology in the treatment of IBD.
      METHODS: A systematic search (PubMed) for experimental studies on the treatment
      of intestinal inflammation using nanotechnology for the delivery of drugs.
      RESULTS AND CONCLUSIONS: The size of the pharmaceutical formulation is inversely
      related to specificity for inflammation. Nanoparticles can penetrate epithelial
      and inflammatory cells resulting in much higher, effective and long-acting
      concentrations than can be obtained using conventional delivery systems. From a
      practical point of view, this should lead to improvements in both efficacy and
      adherence to treatment, providing patients with the prospect of stable and
      prolonged remissions with reduced drug loadings. Reduced systemic side effects
      could also be expected.

PMID- 24686096
TI  - Epidemiology and control of echinococcosis in central Asia, with particular
      reference to the People's Republic of China.
AB  - At least 270 million people (58% of the total population) are at risk of cystic
      echinococcosis (CE) in Central Asia including areas of Mongolia, Kazakhstan,
      Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, Afghanistan, Iran, Pakistan and
      western China. The annual surgical incidence rate in Uzbekistan and Tadjikistan
      has been estimated to be as high as 25-27 cases/100,000 with the highest
      prevalence reaching 10% (range from 0.8 to 11.9%) in some Tibetan communities in
      western China. Echinococcus transmission in the region is largely associated with
      social factors including limited community knowledge of echinococcosis, small
      scale household animal production, home killing of livestock, and the feeding of
      dogs with uncooked offal. Alveolar echinococcosis (AE) is also endemic in Central
      Asia and is recognized as a major problem in some Tibetan communities with up to
      6% of villagers infected in some villages. In western China, 5-30% of the
      population are seropositive against E. granulosus antigens, indicating that a
      large number of individuals have been exposed to the parasite. Although
      echinococcosis control programs have been initiated in some countries in Central
      Asia, control efforts are generally fragmented and uncoordinated. Monthly
      deworming of dogs with praziquantel (PZQ), as a key measure to control the
      Echinococcus parasites, has been used in western China. However, the approach has
      proven difficult in local semi-nomadic communities. Additional control measures
      including health education, domestic livestock animal treatment/vaccination and
      dog vaccination are needed in CE-endemic areas to accelerate progress. 

PMID- 24686098
TI  - A comparison of the 12s rule and Bayesian approach for quality control:
      application to one-stage clotting factor VIII assay.
AB  - An ideal medical biology internal quality control (IQC) plan should both monitor
      the laboratory methods efficiently and implement the relevant clinical-biological
      specifications. However, many laboratories continue to use the 12s quality
      control rule without considering the high risk of false rejection and without
      considering the relationship of analytical performance to quality requirements.
      Alternatively, one can move to the Bayesian arena, enabling probabilistic
      quantification of the information coming in, on a daily basis from the
      laboratory's IQC tests, and taking into account the laboratory's medical and
      economic contexts. Using the example of one-stage clotting factor VIII assay, the
      present study compares frequentist (12s quality control rule) and Bayesian IQC
      management with respect to prescriber requirements, process start-up phase
      issues, and abnormal scenarios in IQC results. To achieve comparable confidence,
      the traditional 12s quality control rule requires more data than the Bayesian
      approach in order to detect an increase in the random or systematic error of the
      method. Moreover, the Bayesian IQC management approach explicitly implements
      respect of prescriber requirements in terms of calculating the probability that
      the variable in question lies in a given predefined interval: for example, the
      factor VIII concentration required after knee surgery in a hemophilia patient. 

PMID- 24686097
TI  - Update on immunologic and molecular diagnosis of human strongyloidiasis.
AB  - Human strongyloidiasis is an intestinal parasitosis that may affect 100 million
      individuals. However, the prevalence rates of this infection may represent
      smaller values than the actual data, mainly due to difficulties in its diagnosis.
      The aim of this study was to update the immunological and molecular methods
      applied to the diagnosis of human strongyloidiasis. There is a great diversity of
      techniques used in the diagnosis of this parasitosis, such as immunofluorescence
      antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), immunoblotting,
      luciferase immunoprecipitation system (LIPS), dispstick and polymerase chain
      reaction (PCR), all with advantages and disadvantages, and with unique features
      for specific purposes. Considering the magnitude of strongyloidiasis and the
      importance of early diagnosis, due to the possibility of chronicity and
      hyperinfection, this study analyzes the different methods currently employed, and
      demonstrates the necessity of developing innovative methodologies, which also
      maintain diagnostic accuracy, particularly for regions with limited technological
      resources. 

PMID- 24686099
TI  - IgG kappa monoclonal gammopathy of undetermined significance presenting as
      acquired type III Von Willebrand syndrome.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder associated
      with hematoproliferative disorders, autoimmune conditions, neoplasia and
      cardiovascular disorders that often present a diagnostic challenge. Monoclonal
      gammopathy of undetermined significance (MGUS) is one of the most common causes
      of AVWS that typically presents later in life with mucocutaneous or postsurgical
      bleeding and multimers consistent with type I or II von Willebrand disease (VWD).
      Here, we present the case of a patient with a 32-year history of type III VWD
      that was ultimately found to be AVWS related to an IgG MGUS. In this case report,
      we highlight the diagnostic challenges of AVWS to ensure proper identification
      and potentially lifesaving treatment of this rare disorder. 

PMID- 24686100
TI  - Mean platelet volume is related with ischemic stroke in patients with sinus
      rhythm.
AB  - Stroke is the leading cause of disability worldwide. It is known that atrial
      fibrillation and left atrial enlargement contribute ischemic stroke, and mean
      platelet volume (MPV) increases in patients with ischemic stroke and atrial
      fibrillation. We aimed to determine whether higher MPV is associated with
      ischemic stroke in patients with sinus rhythm. We evaluated 74 patients in sinus
      rhythm and with ischemic stroke (Group 1) and 90 age-matched and sex-matched
      healthy individuals as control group (Group 2). After physical and
      echocardiographic examination, 24-48 h Holter monitoring and complete blood
      counts were studied. There were no statistically significant differences in age,
      sex rates, and comorbidities between groups. Left atrial diameter was higher in
      Group 1 than Group 2 (P = 0.001), but both were in normal range. MPV was
      significantly higher in Group 1 (P < 0.001) and was an independent determinant
      [odds ratio (OR): 1.840; P < 0.001; 95% confidence interval (CI) 1.330-2.545] of
      ischemic stroke with left atrial (OR: 1.138; P = 0.006; 95% CI 1.037-1.248). In
      conclusion, higher MPV is associated with acute ischemic stroke in patients with
      sinus rhythm and without heart failure or left atrial enlargement. MPV and left
      atrial diameter are independent predictors of ischemic stroke in this patient
      population. 

PMID- 24686101
TI  - Perioperative and peripartum prevention of venous thromboembolism in patients
      with hereditary antithrombin deficiency using recombinant antithrombin therapy.
AB  - Recombinant human antithrombin (rhAT; ATryn), isolated from the milk of
      transgenic goats, provides an alternative to human plasma-derived antithrombin
      (AT) concentrate for perioperative and peripartum prophylaxis of venous
      thromboembolism (VTE) in patients with hereditary AT deficiency. Optimized rhAT
      dosing algorithms and improved plasma AT monitoring protocol were used in an open
      label, single-arm, multinational, pivotal safety and efficacy study that was
      conducted in patients with hereditary AT deficiency in perioperative and
      peripartum settings. Loading and maintenance doses were calculated on the basis
      of pretreatment AT activity levels. Specific dosing regimens were used for
      pregnant and surgical patients; rhAT was to be given for at least 3 days and for
      14 days or less. The primary efficacy end point was the incidence of any
      thromboembolic event during rhAT therapy or within 7 days of rhAT
      discontinuation. Safety and AT activity levels were secondary end points. Six
      surgical and 12 pregnant patients were treated for a median of 3.2 days (range
      0.9-14 days). With the optimized dosing regimens, a median of 1 dose adjustment
      (range 0-6 dose adjustments) was needed to maintain AT activity levels within 80
      120% of normal. No confirmed VTEs occurred during treatment or in the subsequent
      7 days. Overall, rhAT was well tolerated, but some bleeding complications
      occurred after rhAT discontinuation and anticoagulation reinstitution. No
      antibodies to rhAT or goat milk proteins were detected. Perioperative and
      peripartum prophylactic rhAT therapy in patients with hereditary AT deficiency is
      well tolerated and effective in preventing VTE. 

PMID- 24686102
TI  - Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic
      stroke.
AB  - Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu
      polymorphism of its potentially active A subunit (FXIII-A) leads to faster
      activation of FXIII, influences clot structure and provides a moderate protection
      against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on
      the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few
      studies with contradictory results. In all previous studies, only patients
      surviving AIS were enrolled and sex-specific effects were not explored. In this
      retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu
      polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic
      determinations in the case of 316 patients who died of AIS were carried out on
      paraffin-embedded tissue specimens. Genetic analyses for population controls,
      patients with history of AIS and sex-matched controls were performed on extracted
      genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild
      type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not
      different significantly between the patients with fatal AIS and their respective
      controls. Logistic regression analysis with age as co-variant demonstrated that
      in women, homozygous presentation of Leu34 allele represented a more than three
      fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII
      A Val34Leu polymorphism does not influence the occurrence of AIS, but has an
      effect on the severity of its outcome. This effect is sex-specific and in
      homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu
      polymorphism seem to prevail. 

PMID- 24686103
TI  - Impact of the national venous thromboembolism risk assessment tool in secondary
      care in England: retrospective population-based database study.
AB  - Venous thromboembolism (VTE) is a common and important cause of death in hospital
      patients. We therefore investigated possible associations between the
      introduction of the compulsory national VTE risk assessment tool in England in
      2010 and patient outcomes. A retrospective database study, using data from the
      Health and Social Care Information Centre and Office of National Statistics, was
      undertaken. The main outcome measures were VTE-related secondary diagnosis rates,
      30-day and 90-day readmission rates and mortality rates. The observed mean VTE
      related secondary diagnosis rate for 2011-2012 was 91% of the rate estimated from
      a linear regression model of the data for 2006-2007 to 2010-2011 (P = 0.001).
      Similarly, the observed mean 30-day VTE-related readmission rate for 2011 was 96%
      of the estimated rate (P = 0.067) and the observed mean 90-day VTE-related
      readmission rate for 2011 was 96% of the estimated rate (P = 0.022). The observed
      annual VTE-related national mortality rate was 91% of the estimated rate for 2011
      and 92% of the estimated rate for 2012. This study shows a reduction in VTE
      related secondary diagnoses and readmissions among adults admitted to hospital,
      and a reduction in VTE-related population mortality, since the introduction of a
      national VTE risk assessment screening tool in England. Despite some study
      limitations, this suggests that the concerted effort made by NHS England to
      improve prevention of hospital-acquired VTE has been successful.

PMID- 24686104
TI  - Conservative treatment of femoral neuropathy following retroperitoneal
      hemorrhage: a case report and review of literature.
AB  - Anticoagulant drugs are used to reduce the incidence of thromboembolic events in
      patients at risk. However, minor and major bleeding complications may occur
      during anticoagulation therapy. Femoral neuropathy secondary to retroperitoneal
      hematoma is a well known complication of anticoagulant drugs. However, treatment
      of these patients is still controversial, both conservative and surgical
      treatments have been advocated. Herein, we report a male patient receiving
      warfarin for 7 years who developed femoral neuropathy due to retroperitoneal
      hematoma and was successfully treated with conservative methods. We suggest that
      conservative treatment and appropriate rehabilitation program should be given to
      the patients who do not demonstrate any signs of a continued bleeding and any
      progressive neurological deficits. 

PMID- 24686105
TI  - An evaluation of the effectiveness of recruitment methods: the staying well after
      depression randomized controlled trial.
AB  - BACKGROUND: Randomized controlled trials (RCTs) are widely accepted as being the
      most efficient way of investigating the efficacy of psychological therapies.
      However, researchers conducting RCTs commonly report difficulties in recruiting
      an adequate sample within planned timescales. In an effort to overcome
      recruitment difficulties, researchers often are forced to expand their
      recruitment criteria or extend the recruitment phase, thus increasing costs and
      delaying publication of results. Research investigating the effectiveness of
      recruitment strategies is limited, and trials often fail to report sufficient
      details about the recruitment sources and resources utilized. PURPOSE: We
      examined the efficacy of strategies implemented during the Staying Well after
      Depression RCT in Oxford to recruit participants with a history of recurrent
      depression. METHODS: We describe eight recruitment methods utilized and two
      further sources not initiated by the research team and examine their efficacy in
      terms of (1) the return, including the number of potential participants who
      contacted the trial and the number who were randomized into the trial; (2) cost
      effectiveness, comprising direct financial cost and manpower for initial contacts
      and randomized participants; and (3) comparison of sociodemographic
      characteristics of individuals recruited from different sources. RESULTS: Poster
      advertising, web-based advertising, and mental health worker referrals were the
      cheapest methods per randomized participant; however, the ratio of randomized
      participants to initial contacts differed markedly per source. Advertising
      online, via posters, and on a local radio station were the most cost-effective
      recruitment methods for soliciting participants who subsequently were randomized
      into the trial. Advertising across many sources (saturation) was found to be
      important. LIMITATIONS: It may not be feasible to employ all the recruitment
      methods used in this trial to obtain participation from other populations, such
      as those currently unwell, or in other geographical locations. Recruitment source
      was unavailable for participants who could not be reached after the initial
      contact. Thus, it is possible that the efficiency of certain methods of
      recruitment was poorer than estimated. Efficacy and costs of other recruitment
      initiatives, such as providing travel expenses to the in-person eligibility
      assessment and making follow-up telephone calls to candidates who contacted the
      recruitment team but could not be screened promptly, were not analysed.
      CONCLUSION: Website advertising resulted in the highest number of randomized
      participants and was the second cheapest method of recruiting. Future research
      should evaluate the effectiveness of recruitment strategies for other samples to
      contribute to a comprehensive base of knowledge for future RCTs.

PMID- 24686106
TI  - Recruitment of participants to a multiple sclerosis trial: the CombiRx
      experience.
AB  - BACKGROUND: and purpose Participant recruitment is central to all clinical
      trials. Any delay in recruitment affects the completion and ultimate success of
      the trial. We report our experience with patient screening and randomization in
      CombiRx, which may inform the design of other trials. CombiRx was a multicenter,
      phase III, double-blind, randomized clinical trial comparing the combined use of
      interferon beta-1a and glatiramer acetate to either agent alone in patients with
      relapsing-remitting multiple sclerosis (RRMS). This trial was launched in January
      2005 in 69 centers in the United States and Canada under a co-operative agreement
      with the National Institute of Neurological Disorders and Stroke (NINDS). The
      goal was to recruit 1000 patients over 1.5 years after a 6-month start-up period.
      Instead, the investigators required 4.25 years to enroll 1008 patients. METHODS:
      During this trial, we assessed the effectiveness of various recruitment
      strategies, utility of rescreening prior screen failures, and potential factors
      and strategies used in study conduct, research, and infrastructure, all of which
      affected recruitment of participants and ultimately time to completion of
      CombiRx. We particularly were interested in the variability in time to site
      initiation between academic centers and private practice sites. RESULTS:
      Physicians who were directly involved in the medical care of patients with RRMS
      were the primary source of patients recruited to CombiRx. A flexible study design
      that allowed for rescreening of the initial screen failures after a period of
      time was useful due to the relapsing/remitting course of the disease. Academic
      centers took longer to implement the trial than the private practice centers, but
      once sites were approved for enrollment, there was no important difference in the
      number of participants enrolled. LIMITATIONS: The CombiRx trial was conducted
      during a period when multiple new medications were being tested, thus affecting
      the pace of recruitment and limiting ability to generalize our experiences.
      However, the lessons we learned about process are relevant. CONCLUSION:
      Participants can be enrolled successfully in a clinical trial for RRMS, but
      factors affecting the time to achieve the requirements needed to start screening
      can be unpredictable and problematic. Prospective planning by the sponsors and
      investigators, use of central institutional review boards (IRBs), master trial
      agreements and secure remote desktop access to the trial database may expedite
      trial implementation and participant recruitment. A good scientific research
      question with flexible study design and active involvement of the clinicians are
      important factors driving recruitment. Clinical trials can be implemented
      successfully both in private practices and at academic centers, a consideration
      when selecting sites.

PMID- 24686107
TI  - A community consultation survey to evaluate support for and success of the
      IMMEDIATE trial.
AB  - BACKGROUND: The IMMEDIATE (Immediate Myocardial Metabolic Enhancement During
      Initial Assessment and Treatment in Emergency care) Trial, a randomized
      controlled double-blind clinical effectiveness trial of glucose-insulin-potassium
      (GIK) administered in ambulances in the out-of-hospital setting, used the
      Exception from Informed Consent Requirements (EFIC) for Emergency Research under
      Title 21 of the Code of Federal Regulations. EFIC requirements include community
      consultation that typically involves using a variety of communication methods and
      venues to inform the public of the research and to receive their feedback.
      Although not the primary purpose of the community consultation process, a common
      concern to research sponsors, staff, and institutional review boards (IRBs) is
      whether there will be a sufficient number of participants to justify mounting a
      study in their community. Information from community consultation regarding the
      community acceptance might inform this question. PURPOSE: We evaluated the
      utility of telephone survey data done as part of the EFIC process as a way to
      project the ultimate rate of trial participant enrollment. METHODS: A telephone
      survey community consultation process was undertaken in nine communities planning
      to be IMMEDIATE Trial sites using a representative sampling of the target
      population in the areas covered by participating emergency medical service (EMS)
      agencies. Survey respondents were read a description of the planned study and its
      informed consent approach that included the option for patients to decline
      participation in the trial while being transported for acute care in an
      ambulance. Survey respondents were then asked whether they would object to
      participating in the study. At the conclusion of actual trial enrollment, the
      Coordinating Center compared the survey results with the actual rates of
      enrollment at each site. RESULTS: Approximately 200 (range = 200-271) respondents
      completed the survey in each of the study communities. Of 2079 survey
      respondents, 68% (range = 61%-75%) said that they would not object to
      participating in the trial if experiencing a heart attack, and 85% (range = 79%
      89%) said that they would allow the study to be done in their community. During
      actual trial enrollment in the communities, 79% (range = 63%-91%) of the 828
      potential participants agreed in the ambulance to have the study drug started and
      provided informed consent at the hospital, an average of 13 percentage-points
      higher than projected by the survey (95% confidence interval (CI): 9%-17%), 19%
      higher on a relative scale (CI: 14%-25%). CONCLUSIONS: The survey-based approach
      to community consultation proved to be an efficient way to obtain representative
      input from potential clinical trial participants. The survey data generated a
      relatively good and conservative estimate of the ultimate rate of trial
      enrollment. This information could be useful to investigators and IRBs in
      projecting enrollment for clinical trials using EFIC.

PMID- 24686108
TI  - Enrollment of racially/ethnically diverse participants in traumatic brain injury
      trials: effect of availability of exception from informed consent.
AB  - BACKGROUND: The Final Rule regulations were developed to allow exception from
      informed consent (EFIC) to enable clinical trial research in emergency settings
      where major barriers exist for informed consent. There is little known evidence
      of the effect of the Final Rule in minority enrollment in clinical trials,
      particularly in traumatic brain injury (TBI) trials. A clinical trial funded by
      the National Institute of Neurological Disorders and Stroke was conducted to
      study the effects of erythropoietin on cerebral vascular dysfunction and anemia
      in subjects with TBI. There were periods of time when EFIC was and was not
      available for enrollment into the study. PURPOSE: To explore the effect of EFIC
      availability on TBI trial enrollment of minority versus non-minority subjects.
      METHODS: Minority status of screened (n = 289) and enrolled (n = 191) TBI
      subjects was determined for this study. We tested for the presence of a minority
      and EFIC availability interaction in a multiple logistic regression model after
      controlling for EFIC and minority group main effects and other covariates.
      RESULTS: An interaction between the availability of EFIC minority and non
      minority enrollment was not detected (odds ratio = 1.22; 95% confidence interval
      (CI) = 0.29-5.16). LIMITATIONS: Our study was conducted at a single site, and the
      CI for the EFIC and minority interaction term was wide. Therefore, a small
      interaction effect cannot be ruled out. CONCLUSION: EFIC increased the odds of
      being enrolled regardless of minority status.

PMID- 24686109
TI  - Graph theoretical analysis reveals disrupted topological properties of whole
      brain functional networks in temporal lobe epilepsy.
AB  - OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common forms of drug
      resistant epilepsy. Previous studies have indicated that the TLE-related
      impairments existed in extensive local functional networks. However, little is
      known about the alterations in the topological properties of whole brain
      functional networks. METHOD: In this study, we acquired resting-state BOLD-fMRI
      (rsfMRI) data from 26 TLE patients and 25 healthy controls, constructed their
      whole brain functional networks, compared the differences in topological
      parameters between the TLE patients and the controls, and analyzed the
      correlation between the altered topological properties and the epilepsy duration.
      RESULTS: The TLE patients showed significant increases in clustering coefficient
      and characteristic path length, but significant decrease in global efficiency
      compared to the controls. We also found altered nodal parameters in several
      regions in the TLE patients, such as the bilateral angular gyri, left middle
      temporal gyrus, right hippocampus, triangular part of left inferior frontal
      gyrus, left inferior parietal but supramarginal and angular gyri, and left
      parahippocampus gyrus. Further correlation analysis showed that the local
      efficiency of the TLE patients correlated positively with the epilepsy duration.
      CONCLUSION: Our results indicated the disrupted topological properties of whole
      brain functional networks in TLE patients. SIGNIFICANCE: Our findings indicated
      the TLE-related impairments in the whole brain functional networks, which may
      help us to understand the clinical symptoms of TLE patients and offer a clue for
      the diagnosis and treatment of the TLE patients.

PMID- 24686110
TI  - Update on rituximab: an established treatment for all immune-mediated kidney
      diseases?
AB  - Rituximab, a monoclonal antibody directed against the CD20 antigen, found on
      certain B-cell subsets, results in significant B-cell depletion and has been
      increasingly used in immune-mediated renal disease and transplantation. Although
      originally applied to what were considered antibody-mediated diseases, it has
      become clear that auto- and alloreactive B cells contribute in many ways to
      immune dysfunction, and the benefit of B-cell depletion extends beyond reduction
      in auto- or alloantibody levels. Most positive data regarding the benefit of
      rituximab in immune-mediated kidney disease have come from uncontrolled cohort
      studies, with the only positive controlled clinical trials demonstrating efficacy
      for the treatment of systemic vasculitis. While negative trials may have
      potentially missed clinical effects due to trial design, there may be significant
      differences in responses in different diseases or lack of efficacy due to
      therapeutic overlap when used with certain drug combinations. Rituximab is a
      novel treatment that provides a clear alternative for patients in different
      clinical situations, and allows for customization of therapy. However, much
      remains to be understood as to how best to use it in a cost-effective manner,
      when not to use it, and what the long-term impact of therapy may be.

PMID- 24686111
TI  - Pepper suppressor of the G2 allele of skp1 interacts with the receptor-like
      cytoplasmic kinase1 and type III effector AvrBsT and promotes the hypersensitive
      cell death response in a phosphorylation-dependent manner.
AB  - Xanthomonas campestris pv vesicatoria type III effector protein, AvrBsT, triggers
      hypersensitive cell death in pepper (Capsicum annuum). Here, we have identified
      the pepper SGT1 (for suppressor of the G2 allele of skp1) as a host interactor of
      AvrBsT and also the pepper PIK1 (for receptor-like cytoplasmic kinase1). PIK1
      specifically phosphorylates SGT1 and AvrBsT in vitro. AvrBsT specifically binds
      to the CHORD-containing protein and SGT1 domain of SGT1, resulting in the
      inhibition of PIK1-mediated SGT1 phosphorylation and subsequent nuclear transport
      of the SGT1-PIK1 complex. Liquid chromatography-tandem mass spectrometry of the
      proteolytic peptides of SGT1 identified the residues serine-98 and serine-279 of
      SGT1 as the major PIK1-mediated phosphorylation sites. Site-directed mutagenesis
      of SGT1 revealed that the identified SGT1 phosphorylation sites are responsible
      for the activation of AvrBsT-triggered cell death in planta. SGT1 forms a
      heterotrimeric complex with both AvrBsT and PIK1 exclusively in the cytoplasm.
      Agrobacterium tumefaciens-mediated coexpression of SGT1 and PIK1 with avrBsT
      promotes avrBsT-triggered cell death in Nicotiana benthamiana, dependent on PIK1.
      Virus-induced silencing of SGT1 and/or PIK1 compromises avrBsT-triggered cell
      death, hydrogen peroxide production, defense gene induction, and salicylic acid
      accumulation, leading to the enhanced bacterial pathogen growth in pepper.
      Together, these results suggest that SGT1 interacts with PIK1 and the bacterial
      effector protein AvrBsT and promotes the hypersensitive cell death associated
      with PIK1-mediated phosphorylation in plants. 

PMID- 24686112
TI  - Dynamics and organization of cortical microtubules as revealed by superresolution
      structured illumination microscopy.
AB  - Plants employ acentrosomal mechanisms to organize cortical microtubule arrays
      essential for cell growth and differentiation. Using structured illumination
      microscopy (SIM) adopted for the optimal documentation of Arabidopsis
      (Arabidopsis thaliana) hypocotyl epidermal cells, dynamic cortical microtubules
      labeled with green fluorescent protein fused to the microtubule-binding domain of
      the mammalian microtubule-associated protein MAP4 and with green fluorescent
      protein-fused to the alpha tubulin6 were comparatively recorded in wild-type
      Arabidopsis plants and in the mitogen-activated protein kinase mutant mpk4
      possessing the former microtubule marker. The mpk4 mutant exhibits extensive
      microtubule bundling, due to increased abundance and reduced phosphorylation of
      the microtubule-associated protein MAP65-1, thus providing a very useful genetic
      tool to record intrabundle microtubule dynamics at the subdiffraction level. SIM
      imaging revealed nano-sized defects in microtubule bundling, spatially resolved
      microtubule branching and release, and finally allowed the quantification of
      individual microtubules within cortical bundles. Time-lapse SIM imaging allowed
      the visualization of subdiffraction, short-lived excursions of the microtubule
      plus end, and dynamic instability behavior of both ends during free, intrabundle,
      or microtubule-templated microtubule growth and shrinkage. Finally, short, rigid,
      and nondynamic microtubule bundles in the mpk4 mutant were observed to glide
      along the parent microtubule in a tip-wise manner. In conclusion, this study
      demonstrates the potential of SIM for superresolution time-lapse imaging of plant
      cells, showing unprecedented details accompanying microtubule dynamic
      organization. 

PMID- 24686114
TI  - Mechanisms of pollution induced community tolerance in a soil microbial community
      exposed to Cu.
AB  - Pollution induced community tolerance (PICT) to Cu(2+), and co-tolerance to
      nanoparticulate Cu, ionic silver (Ag(+)), and vancomycin were measured in field
      soils treated with Cu(2+) 15 years previously. EC50 values were determined using
      substrate induced respiration and correlations made against soil physicochemical
      properties, microbial community structure, physiological status (qCO2; metabolic
      quotient), and abundances of genes associated with metal and antibiotic
      resistance. Previous level of exposure to copper was directly (P < 0.05)
      associated with tolerance to addition of new Cu(2+), and also of nanoparticle Cu.
      However, Cu-exposed communities had no co-tolerance to Ag(+) and had increased
      susceptibly to vancomycin. Increased tolerance to both Cu correlated (P < 0.05)
      with increased metabolic quotient, potentially indicating that the community
      directed more energy towards cellular maintenance rather than biomass production.
      Neither bacterial or fungal community composition nor changes in the abundance of
      genes involved with metal resistance were related to PICT or co-tolerance
      mechanisms. 

PMID- 24686113
TI  - Secreted fungal effector lipase releases free fatty acids to inhibit innate
      immunity-related callose formation during wheat head infection.
AB  - The deposition of the (1,3)-beta-glucan cell wall polymer callose at sites of
      attempted penetration is a common plant defense response to intruding pathogens
      and part of the plant's innate immunity. Infection of the Fusarium graminearum
      disruption mutant Deltafgl1, which lacks the effector lipase FGL1, is restricted
      to inoculated wheat (Triticum aestivum) spikelets, whereas the wild-type strain
      colonized the whole wheat spike. Our studies here were aimed at analyzing the
      role of FGL1 in establishing full F. graminearum virulence. Confocal laser
      scanning microscopy revealed that the Deltafgl1 mutant strongly induced the
      deposition of spot-like callose patches in vascular bundles of directly
      inoculated spikelets, while these callose deposits were not observed in
      infections by the wild type. Elevated concentrations of the polyunsaturated free
      fatty acids (FFAs) linoleic and alpha-linolenic acid, which we detected in F.
      graminearum wild type-infected wheat spike tissue compared with Deltafgl1
      infected tissue, provided clear evidence for a suggested function of FGL1 in
      suppressing callose biosynthesis. These FFAs not only inhibited plant callose
      biosynthesis in vitro and in planta but also partially restored virulence to the
      Deltafgl1 mutant when applied during infection of wheat spikelets. Additional FFA
      analysis confirmed that the purified effector lipase FGL1 was sufficient to
      release linoleic and alpha-linolenic acids from wheat spike tissue. We concluded
      that these two FFAs have a major function in the suppression of the innate
      immunity-related callose biosynthesis and, hence, the progress of F. graminearum
      wheat infection. 

PMID- 24686115
TI  - Analysis of petroleum contaminated soils by spectral modeling and pure response
      profile recovery of n-hexane.
AB  - This pilot study compared penalized spline regression (PSR) and random forest
      (RF) regression using visible and near-infrared diffuse reflectance spectroscopy
      (VisNIR DRS) derived spectra of 164 petroleum contaminated soils after two
      different spectral pretreatments [first derivative (FD) and standard normal
      variate (SNV) followed by detrending] for rapid quantification of soil petroleum
      contamination. Additionally, a new analytical approach was proposed for the
      recovery of the pure spectral and concentration profiles of n-hexane present in
      the unresolved mixture of petroleum contaminated soils using multivariate curve
      resolution alternating least squares (MCR-ALS). The PSR model using FD spectra
      (r(2) = 0.87, RMSE = 0.580 log10 mg kg(-1), and residual prediction deviation =
      2.78) outperformed all other models tested. Quantitative results obtained by MCR
      ALS for n-hexane in presence of interferences (r(2) = 0.65 and RMSE 0.261 log10
      mg kg(-1)) were comparable to those obtained using FD (PSR) model. Furthermore,
      MCR ALS was able to recover pure spectra of n-hexane. 

PMID- 24686116
TI  - The prevalence of wheezing and its association with serum zinc concentration in
      children and adolescents in Brazil.
AB  - OBJECTIVE: To assess the influence of zinc serum status on the prevalence of
      wheezing in a sample of children and adolescents in Northeastern Brazil. RESEARCH
      METHODS AND PROCEDURES: This is a cross-sectional study which included 592
      students of 6-12 years old, from the public elementary schools of Sao Francisco
      do Conde, Bahia, Northeastern Brazil. Report of wheezing in the past 12 months
      was collected using a questionnaire of the International Study of Asthma and
      Allergies in Childhood Program (ISAAC) phase III, adapted to Portuguese. The
      determination of serum Zn levels was performed using a flame atomic absorption
      spectrometer. Data on anthropometric status, level of physical activity, pubertal
      development and socioeconomic information, for each participant were obtained.
      Multivariate logistic regression analyses were used to assess the associations of
      interest. RESULTS: Of the students, 8.6% (95% CI 6.30-10.9) reported having
      wheezing. The mean (SD) serum zinc level was 114 (22.9 MUg/dL). The results of
      the multiple logistic regression analysis showed, after adjustments, positive and
      significant association between low serum zinc levels and wheezing. Students
      categorized as being below the median for serum Zn concentration presented an
      almost 1.9-fold increase in the wheezing prevalence ratio (OR=1.9; 95% CI 1.03
      3.53). CONCLUSION: The main findings of this study suggest that the level of zinc
      may influence the risk of wheezing in late childhood on the study population.

PMID- 24686117
TI  - Misfolded proteins, mitochondrial dysfunction, and neurodegenerative diseases.

PMID- 24686118
TI  - Emergence of the scale-invariant proportion in a flock from the metric
      topological interaction.
AB  - Recently, it has become possible to more precisely analyze flocking behavior.
      Such research has prompted a reconsideration of the notion of neighborhoods in
      the theoretical model. Flocking based on topological distance is one such result.
      In a topological flocking model, a bird does not interact with its neighbors on
      the basis of a fixed-size neighborhood (i.e., on the basis of metric distance),
      but instead interacts with its nearest seven neighbors. Cavagna et al., moreover,
      found a new phenomenon in flocks that can be explained by neither metric distance
      nor topological distance: they found that correlated domains in a flock were
      larger than the metric and topological distance and that these domains were
      proportional to the total flock size. However, the role of scale-free correlation
      is still unclear. In a previous study, we constructed a metric-topological
      interaction model on three-dimensional spaces and showed that this model
      exhibited scale-free correlation. In this study, we found that scale-free
      correlation in a two-dimensional flock was more robust than in a three
      dimensional flock for the threshold parameter. Furthermore, we also found a
      qualitative difference in behavior from using the fluctuation coherence, which we
      observed on three-dimensional flocking behavior. Our study suggests that two
      dimensional flocks try to maintain a balance between the flock size and flock
      mobility by breaking into several smaller flocks. 

PMID- 24686120
TI  - Histone lysine methylation and chromatin replication.
AB  - In eukaryotic organisms, the replication of the DNA sequence and its organization
      into chromatin are critical to maintain genome integrity. Chromatin components,
      such as histone variants and histone post-translational modifications, along with
      the higher-order chromatin structure, impact several DNA metabolic processes,
      including replication, transcription, and repair. In this review we focus on
      lysine methylation and the relationships between this histone mark and chromatin
      replication. We first describe studies implicating lysine methylation in
      regulating early steps in the replication process. We then discuss chromatin
      reassembly following replication fork passage, where the incorporation of a
      combination of newly synthesized histones and parental histones can impact the
      inheritance of lysine methylation marks on the daughter strands. Finally, we
      elaborate on how the inheritance of lysine methylation can impact maintenance of
      the chromatin landscape, using heterochromatin as a model chromatin domain, and
      we discuss the potential mechanisms involved in this process.

PMID- 24686121
TI  - An integrated approach for the identification of USF1-centered transcriptional
      regulatory networks during liver regeneration.
AB  - Liver regeneration after partial hepatectomy (PH) is a synchronized process that
      is precisely controlled by system-wide transcriptional regulatory networks. To
      clarify the transcriptional changes and regulatory networks that involve
      transcription factors (TFs) and their target genes during the priming phase, an
      advanced mouse oligonucleotide array-based transcription factor assay (MOUSE
      OATFA), mRNA microarray analysis, bioinformatic analysis and ChIP-on-chip
      experiments were used. A total of 774 genes were upregulated or downregulated in
      PH liver samples compared with the sham operation (SH) group. Seventeen TFs
      showed significant changes in activity in the regenerating livers, some of which
      have not been extensively studied in previous reports, including upstream
      stimulatory transcription factor 1 (USF1). The TF signatures from MOUSE OATFA
      were combined with mRNA expression profiles and ChIP-on-chip analyses to
      construct experimental transcriptional regulatory networks in regenerating
      livers. USF1-centered regulatory networks were further confirmed by ChIP assays,
      revealing some of its target genes and novel coregulatory networks. The
      combination of MOUSE OATFA with transcriptome profiling and bioinformatic
      analysis represents a novel paradigm for the comprehensive prediction of
      transcriptional coregulatory networks during the early phase of liver
      regeneration. 

PMID- 24686119
TI  - The bromodomain: from epigenome reader to druggable target.
AB  - Lysine acetylation is a fundamental post-translational modification that plays an
      important role in the control of gene transcription in chromatin in an ordered
      fashion. The bromodomain, the conserved structural module present in
      transcription-associated proteins, functions exclusively to recognize acetyl
      lysine on histones and non-histone proteins. The structural analyses of
      bromodomains' recognition of lysine-acetylated peptides derived from histones and
      cellular proteins provide detailed insights into the differences and unifying
      features of biological ligand binding selectivity by the bromodomains. Newly
      developed small-molecule inhibitors targeting bromodomain proteins further
      highlight the functional importance of bromodomain/acetyl-lysine binding as a key
      mechanism in orchestrating molecular interactions and regulation in chromatin
      biology and gene transcription. These new studies argue that modulating
      bromodomain/acetyl-lysine interactions with small-molecule chemicals offer new
      opportunities to control gene expression in a wide array of human diseases
      including cancer and inflammation. This article is part of a Special Issue
      entitled: Molecular mechanisms of histone modification function. 

PMID- 24686122
TI  - Responsible integration of biological and psychosocial models: comments on
      "Genetic associations with intimate partner violence in a sample of hazardous
      drinking men in batterer intervention programs".
AB  - Despite research demonstrating that gene expression differs in response to social
      environmental circumstances, deterministic views of biology are common. Stuart
      and colleagues (2014) encourage readers to think about genetic factors in the
      same dynamic and probabilistic manner that they consider other causes of intimate
      partner violence. Given that participants had co-occurring alcohol problems,
      future studies should evaluate how different genetic polymorphisms uniquely and
      synergistically contribute to heavy drinking and aggression under different socio
      environmental conditions. Psychological expectancies have a powerful impact on
      behavior, thus extreme caution is required before labeling people as genetically
      predisposed to violence. 

PMID- 24686123
TI  - Resisting rape: the effects of victim self-protection on rape completion and
      injury.
AB  - The impact of victim resistance on rape completion and injury was examined
      utilizing a large probability sample of sexual assault incidents, derived from
      the National Crime Victimization Survey (1992-2002), and taking into account
      whether harm to the victim followed or preceded self-protection (SP) actions.
      Additional injuries besides rape, particularly serious injuries, following victim
      resistance are rare. Results indicate that most SP actions, both forceful and
      nonforceful, reduce the risk of rape completion, and do not significantly affect
      the risk of additional injury. 

PMID- 24686124
TI  - Appropriate care for shelter-based abused women: concept mapping with Dutch
      clients and professionals.
AB  - We conducted a concept mapping exercise to gain insight into the perspectives
      held by abused women and professionals with regard to appropriate care in Dutch
      women's shelters. Three brainstorming sessions generated 92 statements that were
      then rated by 56 clients and 51 professionals. A total of 11 clusters were
      identified. The three most important clusters were "help with finding a safe
      house if necessary," "safety and suitable care for the children," and "a
      personalized, respectful approach." The most important statement was "take women
      seriously and treat them with respect." The mapping exercise identified key
      practice-based elements of intervention that should better accommodate the needs
      of shelter-based abused women. We have used these elements in developing a new
      intervention for shelter-based abused women in the Netherlands. 

PMID- 24686127
TI  - "She deserved it": Effects of sexism norms, type of violence, and victim's pre
      assault behavior on blame attributions toward female victims and approval of the
      aggressor's behavior.
AB  - Effects of ambivalent sexism, sexism norms, victim behavior, and type of violence
      on male students' reactions to male violence against women in intimate
      relationships were examined. Participants judged a scenario depicting an act of
      sexual or non-sexual violence against a female partner who had either shown
      overtly sexual or non-sexual behavior toward another man. Generally, high (vs.
      low) hostile sexism, high (vs. low) hostile sexism norm feedback, and victim's
      overtly sexual (vs. non-sexual) behavior led to stronger victim blame and
      perceived approval of the aggressor's behavior. The victim of non-sexual violence
      was blamed more than the rape victim, particularly if she had behaved in an
      overtly sexual manner. 

PMID- 24686126
TI  - Empowering self-defense training.
AB  - The purpose of self-defense training is to expand people's options, yet it is
      often framed as a solely physical, and limiting, response to violence. I draw on
      my own experience as a self-defense instructor and that of others in the self
      defense movement to argue that an empowerment approach to self-defense training
      contributes to the anti-violence movement in multiple ways: providing a pathway
      to increase women's and girls' safety and their potential for becoming powerful
      and effective social change agents right now, providing an informed and embodied
      understanding of violence, and offering comprehensive options to recognize,
      prevent, and interrupt violence. 

PMID- 24686125
TI  - Prevalence and correlates of client-perpetrated abuse among female sex workers in
      two Mexico-U.S. border cities.
AB  - History of abuse has been associated with greater HIV risk among women. This
      study examined client-perpetrated abuse among female sex workers (FSWs) in two
      Mexico-U.S. border cities where HIV prevalence is rising. Among 924 FSWs,
      prevalence of client-perpetrated abuse was 31%. In multivariate logistic
      regression models, intimate partner violence (IPV), psychological distress, and
      having drug-using clients were associated with experiencing client-perpetrated
      abuse. FSWs along the Mexico-U.S. border report frequently experiencing abuse
      from both clients and intimate partners, which may have serious mental health
      consequences. Our findings suggest the need for screening and gender-based
      violence prevention services for Mexican FSWs. 

PMID- 24686128
TI  - From gun politics to self-defense politics: a feminist critique of the great gun
      debate.
AB  - This article calls attention to a problematic binary produced by public debates
      surrounding gun rights and gun control-namely, that women must choose armed self
      protection or no self-protection at all. I argue that both anti- and pro-gun
      discourses, drawing on and reproducing race and class privileges, use assumptions
      about women's physical inferiority to further their agendas. I highlight how both
      sides have used guns as the proxy for self-defense and conclude by calling for a
      shift in public discourse to focus on the broader question of the right to self
      defense rather than the narrower question of gun rights. 

PMID- 24686129
TI  - Estradiol and weight are covariates of paracetamol clearance in young women.
AB  - AIM: Paracetamol clearance differs between pregnant and non-pregnant women and
      between women with or without specific oral contraceptives (OCs). However, an
      association between female sex hormones and paracetamol clearance has never been
      explored. METHODS: In total, 49 women at delivery, 8 female control subjects
      without OC use, historical data of 14 women taking OCs, and 15 postpartum
      observations with and without OCs were pooled to explore covariates of
      paracetamol clearance. All received a single intravenous 2-gram paracetamol dose,
      and blood samples were collected up to 6 h after dosing. High-performance liquid
      chromatography was used to quantify paracetamol. The area under the curve to time
      infinity (AUC0-infinity) was determined and clearance (l/h.m(2)) was calculated
      by dose/ AUC0-infinity. In addition, estradiol and progesterone were quantified
      by ELISA with electro-chemiluminescence. RESULTS: Median paracetamol clearance at
      delivery was significantly higher when compared to postpartum or non-pregnant
      women (11.9 vs. 6.42 and 8.4 l/h.m(2), at least p < 0.05), while an association
      between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001).
      In non-pregnant subjects, there was no impact of OC exposure on paracetamol
      clearance. Multiple regression revealed a linear association (Radj = 0.41, p <
      0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p <
      0.0001). CONCLUSION: Estradiol and weight in part explain the variation in
      paracetamol clearance in young women.

PMID- 24686130
TI  - The Dietary Approaches to Stop Hypertension (DASH) diet affects inflammation in
      childhood metabolic syndrome: a randomized cross-over clinical trial.
AB  - BACKGROUND: The effects of the DASH (Dietary Approaches to Stop Hypertension)
      diet on inflammation in childhood metabolic syndrome (MetS) have still to be
      identified. OBJECTIVE: To examine the effects of the DASH diet on markers of
      systemic inflammation in adolescents with MetS. METHODS: In this randomized,
      cross-over clinical trial, 60 postpubescent girls with MetS were randomly
      assigned to receive either the DASH diet menu cycles or usual dietary advice
      (UDA) for 6 weeks. After a 4-week washout period, participants were crossed over
      to the alternate arm. The DASH diet was designed to maintain the current body
      weight. This diet contained high amounts of fruit, vegetables and low-fat dairy
      products and was low in saturated fats and cholesterol. UDA consisted of general
      oral advice and written information about healthy food choices based on the
      Healthy Eating Plate. Compliance to the DASH diet was assessed through
      quantification of plasma vitamin C levels. Fasting venous blood samples were
      taken 4 times from each participant: at baseline and at the end of each study
      arm. Circulating levels of biomarkers of systemic inflammation were quantified
      according to standard protocols. RESULTS: Mean (SD) age and weight of
      participants was 14.2 years (1.7) and 69 kg (14.5), respectively. Serum vitamin C
      levels tended to increase during the DASH phase compared with the UDA phase (16.8
      +/- 12.9 vs. -13.8 +/- 9.7 ng/dl, respectively, p = 0.06) indicating a relatively
      good compliance to the DASH diet. Adherence to the DASH diet, compared to the
      UDA, had a significant effect on serum high-sensitivity C-reactive protein levels
      (p = 0.002). This effect remained significant even after adjustment for weight
      changes and after further controlling for changes in lipid profiles. We did not
      observe any significant effect of intervention on levels of serum tumor necrosis
      factor-alpha, interleukin (IL)-2, IL-6 and adiponectin, in either the crude or
      adjusted models. There were no significant group*time interactions for any
      dependent variable, except for IL-6; this was close to the significant level.
      CONCLUSION: In summary, consumption of the DASH eating pattern for 6 weeks may
      reduce circulating levels of hs-CRP among adolescents with MetS. Other
      inflammatory markers were not affected by the DASH diet.

PMID- 24686131
TI  - Genetic engineering of crops: a ray of hope for enhanced food security.
AB  - Crop improvement has been a basic and essential chase since organized cultivation
      of crops began thousands of years ago. Abiotic stresses as a whole are regarded
      as the crucial factors restricting the plant species to reach their full genetic
      potential to deliver desired productivity. The changing global climatic
      conditions are making them worse and pointing toward food insecurity. Agriculture
      biotechnology or genetic engineering has allowed us to look into and understand
      the complex nature of abiotic stresses and measures to improve the crop
      productivity under adverse conditions. Various candidate genes have been
      identified and transformed in model plants as well as agriculturally important
      crop plants to develop abiotic stress-tolerant plants for crop improvement. The
      views presented here are an attempt toward realizing the potential of genetic
      engineering for improving crops to better tolerate abiotic stresses in the era of
      climate change, which is now essential for global food security. There is great
      urgency in speeding up crop improvement programs that can use modern
      biotechnological tools in addition to current breeding practices for providing
      enhanced food security. 

PMID- 24686132
TI  - The neural process of perception and evaluation for environmental hazards:
      evidence from event-related potentials.
AB  - Perception and evaluation of environmental hazards are vital for human beings to
      avoid potential hazard. This study used event-related potentials to explore the
      neural temporal features in the human brain during the processing of
      environmental hazard presented by picture stimuli, and we found two stages
      involved in processing pictures with environmental hazard: the relatively early
      automatic hazard perception stage indicated by P200 and the later hazard
      evaluation stage indicated by late positive potential. It provided certain
      evidence for the hazard perception two-stage model. The results indicated
      consistency between neural processing toward word and picture stimuli in the
      hazard evaluation tasks. 

PMID- 24686133
TI  - BMP2 shows neurotrophic effects including neuroprotection against
      neurodegeneration.
AB  - In this study, we found that BMP2 exerts neurotrophic effects, including a
      neuroprotective effect against nocodazole-induced neuritic degeneration, on
      neuronal cells. We also found that BMP2-induced neurotrophic effects are directly
      involved in Smad-dependent signaling as well as PI3K/PTEN-Akt-mTOR signaling.
      Moreover, BMP2-induced neurotrophic effects occur by stabilization of neuronal
      microtubules. Thus, these findings suggest that BMP2 can be a potential
      therapeutic target for nerve injury treatment. 

PMID- 24686134
TI  - Human sex differences in emotional processing of own-race and other-race faces.
AB  - There is evidence that women and men show differences in the perception of
      affective facial expressions. However, none of the previous studies directly
      investigated sex differences in emotional processing of own-race and other-race
      faces. The current study addressed this issue using high time resolution event
      related potential techniques. In total, data from 25 participants (13 women and
      12 men) were analyzed. It was found that women showed increased N170 amplitudes
      to negative White faces compared with negative Chinese faces over the right
      hemisphere electrodes. This result suggests that women show enhanced sensitivity
      to other-race faces showing negative emotions (fear or disgust), which may
      contribute toward evolution. However, the current data showed that men had
      increased N170 amplitudes to happy Chinese versus happy White faces over the left
      hemisphere electrodes, indicating that men show enhanced sensitivity to own-race
      faces showing positive emotions (happiness). In this respect, men might use past
      pleasant emotional experiences to boost recognition of own-race faces. 

PMID- 24686135
TI  - Enriched environment attenuates nicotine self-administration and induces changes
      in DeltaFosB expression in the rat prefrontal cortex and nucleus accumbens.
AB  - Environment enrichment conditions have important consequences on subsequent
      vulnerability to drugs of abuse. The present work examined whether exposure to an
      enriched environment (EE) decreases oral self-consumption of nicotine. Wistar
      rats were housed either in a standard environment (SE, four rats per standard
      cage) or in an EE during 60 days after weaning. EE consisted of eight animals
      housed in larger cages containing a variety of objects such as boxes, toys, and
      burrowing material that were changed three times a week. After this period,
      animals were exposed to nicotine for 3 weeks, where animals chose freely between
      water and a nicotine solution (0.006% in water). Fluid consumption was evaluated
      on a daily basis. DeltaFosB immunohistochemistry in the prefrontal cortex and
      nucleus accumbens was also performed. Rats of the EE group consumed less nicotine
      solution (0.25+/-0.04 mg/kg/day) than SE rats (0.54+/-0.05 mg/kg/day). EE
      increased the number of DeltaFos-immunoreactive (DeltaFos-ir) cells in the
      nucleus accumbens core and shell and in the prefrontal cortex, compared with
      animals in the standard condition. However, rats exposed to nicotine in the SE
      showed higher DeltaFos-ir cells in the nucleus accumbens core and shell than
      nonexposed rats. Nicotine consumption did not modify DeltaFos-ir cells in these
      brain areas in EE animals. These results support the idea of a possible
      protective effect of the EE on reward sensitivity and the development of an
      addictive behavior to nicotine. 

PMID- 24686137
TI  - Response to Selveraj et al.

PMID- 24686136
TI  - Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia.
AB  - Consistent with recent reports indicating that neurons differentiated in vitro
      from human-induced pluripotent stem cells (hiPSCs) are immature relative to those
      in the human brain, gene expression comparisons of our hiPSC-derived neurons to
      the Allen BrainSpan Atlas indicate that they most resemble fetal brain tissue.
      This finding suggests that, rather than modeling the late features of
      schizophrenia (SZ), hiPSC-based models may be better suited for the study of
      disease predisposition. We now report that a significant fraction of the gene
      signature of SZ hiPSC-derived neurons is conserved in SZ hiPSC neural progenitor
      cells (NPCs). We used two independent discovery-based approaches-microarray gene
      expression and stable isotope labeling by amino acids in cell culture (SILAC)
      quantitative proteomic mass spectrometry analyses-to identify cellular phenotypes
      in SZ hiPSC NPCs from four SZ patients. From our findings that SZ hiPSC NPCs show
      abnormal gene expression and protein levels related to cytoskeletal remodeling
      and oxidative stress, we predicted, and subsequently observed, aberrant migration
      and increased oxidative stress in SZ hiPSC NPCs. These reproducible NPC
      phenotypes were identified through scalable assays that can be applied to
      expanded cohorts of SZ patients, making them a potentially valuable tool with
      which to study the developmental mechanisms contributing to SZ. 

PMID- 24686138
TI  - Isolation of mRNAs associated with yeast mitochondria to study mechanisms of
      localized translation.
AB  - Most of mitochondrial proteins are encoded in the nucleus and need to be imported
      into the organelle. Import may occur while the protein is synthesized near the
      mitochondria. Support for this possibility is derived from recent studies, in
      which many mRNAs encoding mitochondrial proteins were shown to be localized to
      the mitochondria vicinity. Together with earlier demonstrations of ribosomes'
      association with the outer membrane, these results suggest a localized
      translation process. Such localized translation may improve import efficiency,
      provide unique regulation sites and minimize cases of ectopic expression. Diverse
      methods have been used to characterize the factors and elements that mediate
      localized translation. Standard among these is subcellular fractionation by
      differential centrifugation. This protocol has the advantage of isolation of
      mRNAs, ribosomes and proteins in a single procedure. These can then be
      characterized by various molecular and biochemical methods. Furthermore,
      transcriptomics and proteomics methods can be applied to the resulting material,
      thereby allow genome-wide insights. The utilization of yeast as a model organism
      for such studies has the advantages of speed, costs and simplicity. Furthermore,
      the advanced genetic tools and available deletion strains facilitate verification
      of candidate factors. 

PMID- 24686139
TI  - Enzymatic functional stability of Zn-contaminated field-collected soils: an
      ecotoxicological perspective.
AB  - Functional stability (FS) is an ecosystem attribute that is increasingly promoted
      in soil health assessment. However, FS is currently assessed comparatively, and
      it is therefore impossible to generate toxicity parameters. Additionally, the FS
      scores in the literature do not consider site and contamination history within
      the score. To address these issues, three new FS scores adapted to an
      ecotoxicological context and based on the Relative Soil Stability Index (RSSI)
      method were developed. The aim of the study was then to determine the FS score(s)
      that best describe the toxicity of metal-contaminated field-collected soils.
      Twenty pairs of Zn-contaminated soils (contaminated and reference soils) were
      collected on the field, and their enzymatic FS (arylsulfatase, protease,
      phosphatase and urease) and metal fractions (total and bioavailable) were
      analyzed. New RSSI-based and existing FS scores were calculated for each enzyme
      and correlated to the Zn fractions. One of the new RSSI-based scores was well
      correlated with the bioavailable labile Zn concentration for the arylsulfatase,
      phosphatase and urease (coefficients of regression higher than 0.50).
      Furthermore, this FS score was not affected by the soil organic matter and
      depended little on other soil properties. Other FS scores were correlated to
      labile Zn for only one enzyme, which varied according to the score. The new RSSI
      based score thus better attributed Zn toxicity to field-collected soils than
      other FS scores. 

PMID- 24686140
TI  - Identifying diffused nitrate sources in a stream in an agricultural field using a
      dual isotopic approach.
AB  - Nitrate (NO3(-)) pollution is a severe problem in aquatic systems in Taihu Lake
      Basin in China. A dual isotope approach (delta(15)NNO3(-) and delta(18)ONO3(-))
      was applied to identify diffused NO3(-) inputs in a stream in an agricultural
      field at the basin in 2013. The site-specific isotopic characteristics of five
      NO3(-) sources (atmospheric deposition, AD; NO3(-) derived from soil organic
      matter nitrification, NS; NO3(-) derived from chemical fertilizer nitrification,
      NF; groundwater, GW; and manure and sewage, M&S) were identified. NO3(-)
      concentrations in the stream during the rainy season [mean+/-standard deviation
      (SD)=2.5+/-0.4mg/L] were lower than those during the dry season (mean+/-SD=4.0+/
      0.5mg/L), whereas the delta(18)ONO3(-) values during the rainy season (mean+/
      SD=+12.3+/-3.60/00) were higher than those during the dry season (mean+/
      SD=+0.9+/-1.90/00). Both chemical and isotopic characteristics indicated that
      mixing with atmospheric NO3(-) resulted in the high delta(18)O values during the
      rainy season, whereas NS and M&S were the dominant NO3(-) sources during the dry
      season. A Bayesian model was used to determine the contribution of each NO3(-)
      source to total stream NO3(-). Results showed that reduced N nitrification in
      soil zones (including soil organic matter and fertilizer) was the main NO3(-)
      source throughout the year. M&S contributed more NO3(-) during the dry season
      (22.4%) than during the rainy season (17.8%). AD generated substantial amounts of
      NO3(-) in May (18.4%), June (29.8%), and July (24.5%). With the assessment of
      temporal variation of diffused NO3(-) sources in agricultural field, improved
      agricultural management practices can be implemented to protect the water
      resource and avoid further water quality deterioration in Taihu Lake Basin. 

PMID- 24686141
TI  - Electrical conductivity and emerging contaminant as markers of surface freshwater
      contamination by wastewater.
AB  - The use of chemical markers of undoubted anthropogenic sources for surface
      freshwater contamination by wastewaters was evaluated employing correlations
      observed between measured physico-chemical parameters as the electrical
      conductivity and the concentration of different emerging organic compounds.
      During the period from April/2011 to April/2012 spatial-temporal variations and
      contamination patterns of two rivers (Pirai and Jundiai rivers), Sao Paulo state,
      Brazil were evaluated. Seven physico-chemical parameters and concentrations of
      different classes of emerging contaminants were determined in samples collected
      in seven field campaigns. The high linear correlation coefficients obtained for
      the compounds diclofenac (r=0.9085), propanolol (r=0.8994), ibuprofen (r=0.8720)
      and atenolol (r=0.7811) with electrical conductivity, also corroborated by
      principal component analysis (PCA), point to the potential use of these compounds
      as markers of investigated surface water contamination by wastewaters. Due to
      specific inputs, these environmental markers showed very good effectiveness for
      the identification and differentiation of water body contamination by discharges
      of treated and untreated urban sewage. 

PMID- 24686142
TI  - Metal contamination in campus dust of Xi'an, China: a study based on multivariate
      statistics and spatial distribution.
AB  - The concentrations of As, Ba, Co, Cr, Cu, Mn, Ni, Pb, V and Zn in campus dust
      from kindergartens, elementary schools, middle schools and universities of Xi'an,
      China were determined by X-ray fluorescence spectrometry. Correlation coefficient
      analysis, principal component analysis (PCA) and cluster analysis (CA) were used
      to analyze the data and to identify possible sources of these metals in the dust.
      The spatial distributions of metals in urban dust of Xi'an were analyzed based on
      the metal concentrations in campus dusts using the geostatistics method. The
      results indicate that dust samples from campuses have elevated metal
      concentrations, especially for Pb, Zn, Co, Cu, Cr and Ba, with the mean values of
      7.1, 5.6, 3.7, 2.9, 2.5 and 1.9 times the background values for Shaanxi soil,
      respectively. The enrichment factor results indicate that Mn, Ni, V, As and Ba in
      the campus dust were deficiently to minimally enriched, mainly affected by nature
      and partly by anthropogenic sources, while Co, Cr, Cu, Pb and Zn in the campus
      dust and especially Pb and Zn were mostly affected by human activities. As and
      Cu, Mn and Ni, Ba and V, and Pb and Zn had similar distribution patterns. The
      southwest high-tech industrial area and south commercial and residential areas
      have relatively high levels of most metals. Three main sources were identified
      based on correlation coefficient analysis, PCA, CA, as well as spatial
      distribution characteristics. As, Ni, Cu, Mn, Pb, Zn and Cr have mixed sources -
      nature, traffic, as well as fossil fuel combustion and weathering of materials.
      Ba and V are mainly derived from nature, but partly also from industrial
      emissions, as well as construction sources, while Co principally originates from
      construction. 

PMID- 24686143
TI  - Avoidance response of Danio rerio to a fungicide in a linear contamination
      gradient.
AB  - The present study examines the ability of juvenile Danio rerio to avoid
      pyrimethanil-contaminated water. An avoidance assay system was used with a
      contamination gradient formed by seven compartments, through which the fish could
      move and choose the preferred compartment(s). Additionally, the influence of fish
      movements in promoting the mixing between compartments and thus disruption of the
      gradient over time was also examined by testing sodium chloride (NaCl) at
      sublethal concentrations. Samples with pyrimethanil were obtained from the
      commercial formulation Mythos(r), which was applied to mesocosm systems. Samples
      of the pyrimethanil-contaminated mesocosms water were collected and a series of
      seven concentrations (0.2 to 1.4mgL(-1) plus a control) diluted with reference
      (uncontaminated) mesocosm water were added to the system to form the gradient.
      After 4h exposure, fish avoidance in the three highest pyrimethanil
      concentrations ranged from 29 to 66%. The 4h-AC50 (concentration at which 50% of
      the fish avoided pyrimethanil after 4h exposure) was 1.10 (confidence interval:
      1.07 to 1.12)mgL(-1). However, the avoidance pattern after 12h was strongly
      reduced and it was not possible to calculate the AC50. This is explained by the
      results of the NaCl experiment, which showed that the movement of fish in the
      system accelerates the mixing of the solutions between compartments. As
      pyrimethanil can trigger avoidance response in D. rerio, this fungicide, even at
      non-lethal concentrations, could be considered an environmental disturber. 

PMID- 24686144
TI  - Factors driving epilithic algal colonization in show caves and new insights into
      combating biofilm development with UV-C treatments.
AB  - The proliferation of epilithic algae that form biofilms in subterranean
      environments, such as show caves, is a major problem for conservators. In an
      effort to reduce the use of chemical cleansers when addressing this problem, we
      proposed investigating the effects of UV-C on combating algal biofilm expansion
      in a cave located in northeastern France (Moidons Cave). First, the biofilms and
      cavity were studied in terms of their algal growth-influencing factors to
      understand the dynamics of colonization in these very harsh environments. Next,
      colorimetric measurements were used both to diagnose the initial colonization
      state and monitor the UV-C-treated biofilms for several months after irradiation.
      The results indicated that passive dispersal vectors of the viable spores and
      cells were the primary factors involved in the cave's algae repartition. The
      illumination time during visits appeared to be responsible for greater
      colonization in some parts of the cave. We also showed that colorimetric
      measurements could be used for the detection of both thin and thick biofilms,
      regardless of the type of colonized surface. Finally, our results showed that UV
      C treatment led to bleaching of the treated biofilm due to chlorophyll
      degradation even one year after UV-C treatment. However, a re-colonization
      phenomenon was colorimetrically and visually detected 16months later, suggesting
      that the colonization dynamics had not been fully halted. 

PMID- 24686145
TI  - Occurrence of acidic pharmaceuticals and personal care products in Turia River
      Basin: from waste to drinking water.
AB  - The occurrence of 21 acidic pharmaceuticals, including illicit drugs, and
      personal care products (PPCPs) in waste, surface and drinking water and in
      sediments of the Turia River Basin (Valencia, Spain) was studied. A liquid
      chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the
      determination of these PPCPs with electrospray (ESI) in negative ionization (NI)
      mode. Ammonium fluoride in the mobile phase improved ionization efficiency by an
      average increase in peak area of 5 compared to ammonium formate or formic acid.
      All studied compounds were detected and their concentration was waste
      water>surface water>drinking water. PPCPs were in waste water treatment plants
      (WWTPs) influents up to 7.26MUgL(-1), dominated by ibuprofen, naproxen and 11-nor
      9-carboxy-Delta9-tetrahydrocannabinol (THCOOH). WWTPs were highly effective in
      removing most of them, with an average removal rate of >90%. PPCPs were still
      detected in effluents in the 6.72-940ngL(-1) range, with the THCOOH,
      triclocarban, gemfibrozil and diclofenac as most prevalent. Similarly,
      diclofenac, gemfibrozil, ibuprofen, naproxen and propylparaben were detected
      quite frequently from the low ngL(-1) range to 7MUgL(-1) in the surface waters of
      Turia River. Ibuprofen, methylparaben, salicylic acid and tetrahydrocannabinol
      (THC) were at concentrations up to 0.85ngg(-1) d.w. in sediments. The discharge
      of WWTP as well as of non-treated waters to this river is a likely explanation
      for the significant amount of PPCPs detected in surface waters and sediments.
      Mineral and tap waters also presented significant amounts (approx. 100ngL(-1)) of
      ibuprofen, naproxen, propylparaben and butylparaben. The occurrence at trace
      levels of several PPCPs in drinking water raises concerns about possible
      implications for human health. 

PMID- 24686146
TI  - An indicator to map diffuse chemical river pollution considering buffer capacity
      of riparian vegetation--a pan-European case study on pesticides.
AB  - Vegetated riparian areas alongside streams are thought to be effective at
      intercepting and controlling chemical loads from diffuse agricultural sources
      entering water bodies. Based on a recently compiled European map of riparian
      zones and a simplified soil chemical balance model, we propose a new indicator at
      a continental scale. QuBES (Qualitative indicator of Buffered Emissions to
      Streams) allows a qualitative assessment of European rivers exposed to pesticide
      input. The indicator consists of normalised pesticide loads to streams computed
      through a simplified steady-state fate model that distinguishes various chemical
      groups according to physico-chemical behaviour (solubility and persistence). The
      retention of pollutants in the buffer zone is modelled according to buffer width
      and sorption properties. While the indicator may be applied for the study of a
      generic emission pattern and for a chemical of generic properties, we demonstrate
      it to the case of agricultural emissions of pesticides. Due to missing geo
      spatial data of pesticide emissions, a total pesticide emission scenario is
      assumed. The QuBES indicator is easy to calculate and requires far less input
      data and parameterisation than typical chemical-specific models. At the same
      time, it allows mapping of (i) riparian buffer permeability, (ii) chemical runoff
      from soils, and (iii) the buffered load of chemicals to the stream network. When
      the purpose of modelling is limited to identifying chemical pollution patterns
      and understanding the relative importance of emissions and natural attenuation in
      soils and stream buffer strips, the indicator may be suggested as a screening
      level, cost-effective alternative to spatially distributed models of higher
      complexity. 

PMID- 24686147
TI  - Organic priority substances and microbial processes in river sediments subject to
      contrasting hydrological conditions.
AB  - Flood and drought events of higher intensity and frequency are expected to
      increase in arid and semi-arid regions, in which temporary rivers represent both
      a water resource and an aquatic ecosystem to be preserved. In this study, we
      explored the variation of two classes of hazardous substances (Polycyclic
      Aromatic Hydrocarbons and Nonylphenols) and the functioning of the microbial
      community in river sediments subject to hydrological fluctuations (Candelaro
      river basin, Italy). Overall, the concentration of pollutants (?PAHs range 8
      275ngg(-1); ?NPs range 299-4858ngg(-1)) suggests a moderate degree of
      contamination. The conditions in which the sediments were tested, flow (high/low)
      and no flow (wet/dry/arid), were associated to significant differences in the
      chemical and microbial properties. The total organic carbon contribution
      decreased together with the stream flow reduction, while the contribution of C
      PAHs and C-NPs tended to increase. NPs were relatively more concentrated in
      sediments under high flow, while the more hydrophobic PAHs accumulated under low
      and no flow conditions. Passing from high to no flow conditions, a gradual
      reduction of microbial processes was observed, to reach the lowest specific
      bacterial carbon production rates (0.06fmolCh(-1)cell(-1)), extracellular enzyme
      activities, and the highest doubling time (40h) in arid sediments. In conclusion,
      different scenarios for the mobilization of pollutants and microbial processes
      can be identified under contrasting hydrological conditions: (i) the mobilization
      of pollutants under high flow and a relatively higher probability for
      biodegradation; (ii) the accumulation of pollutants during low flow and lower
      probability for biodegradation; (iii) the drastic reduction of pollutant
      concentrations under dry and arid conditions, probably independently from the
      microbial activity (abiotic processes). Our findings let us infer that a multiple
      approach has to be considered for an appropriate water resource exploitation and
      a more realistic prevision of the impact of pollutants in temporary waters. 

PMID- 24686148
TI  - Evaluation of pesticide monitoring strategies in agricultural streams based on
      the toxic-unit concept--experiences from long-term measurements.
AB  - The European Water Framework Directive requires surface water bodies to have a
      good chemical and ecological status. Although relatively few pesticides are
      included in the list of priority pollutants, they pose, due to their intrinsic
      biological activity, a significant risk for the integrity of aquatic ecosystems.
      In this context, the pesticide (up to 128 pesticides including some
      transformation products) exposure pattern in four agricultural streams and two
      rivers was determined from 2002 to 2011 under the umbrella of the Swedish
      national monitoring program employing time-proportional and grab sampling
      strategies, respectively. After transforming the measured pesticide
      concentrations into toxic units, the European Uniform Principles for algae
      (chronic), invertebrates and fish (both acute), which are partly employed as
      benchmark for pesticide regulation, were only occasionally (<2%) exceeded.
      Moreover, this evaluation showed no long-term trends over the years. However,
      recent publications suggested that those thresholds are not protective for
      ecosystem structure and function, indicating a risk of up to 20% and 35% of the
      samples from the agricultural streams and the rivers, respectively. Moreover, the
      monitoring data show a continuous but rather low toxic potential of pesticides
      for all three trophic levels throughout the year, which suggests pesticides as an
      evolutionary force in agriculturally impacted aquatic ecosystems. However, the
      flow-triggered sampling, which was implemented as an additional sampling strategy
      in one of the agricultural streams starting in 2006, displayed an up to 7-fold
      underestimation of the maximum concentration in terms of toxic units for daphnids
      and fish during run-off events. The present study thus underpins that the optimal
      sampling design for pesticide monitoring strongly depends on its overall purpose.
      If the long-term exposure pattern is of concern a time-proportional composite
      sampling strategy is recommended, while for an assessment of peak exposures a
      flow-event-triggered high-resolution sampling strategy is superior. 

PMID- 24686149
TI  - Surface plasmon resonance technique for directly probing the interaction of DNA
      and graphene oxide and ultra-sensitive biosensing.
AB  - The binding of DNA with graphene oxide (GO) is important for applications in
      disease diagnosis, genetic screening, and drug discovery. The standard assay
      methods are mainly limited to indirect observation via fluorescence labeling.
      Here we report the use of surface plasmon resonance for direct sensing of DNA/GO
      binding. We show that this can be used for ultra-sensitive detection of single
      stranded DNA (ssDNA). Furthermore, the results provide a more direct probe of
      DNA/GO binding abilities and confirm that hydrogen bonding plays a key role in
      the interaction between GO and ssDNA. This enables to a novel biosensor for
      highly sensitive and selective detection of ssDNA based on indirect competitive
      inhibition assay (ICIA). We report development of such a sensor with a linear
      dynamic range of 10(-14)-10(-6)M, a detection limit of 10fM and a high level of
      stability during repeated regeneration. 

PMID- 24686150
TI  - Dynamic and equilibrium performance of sensors based on short peptide ligands for
      affinity adsorption of human IgG using surface plasmon resonance.
AB  - This paper characterizes the potential of novel hexameric peptide ligands for on
      line IgG detection in bioprocesses. Surface Plasmon Resonance (SPR) was used to
      study the binding of human IgG to the hexameric peptide ligand HWRGWV, which was
      covalently grafted to alkanethiol self-assembled monolayers (SAM) on gold
      surfaces. Peptide coupling on SAMs was verified, followed by covalent grafting of
      peptides with a removable Fmoc or acetylated N-termini via their C-termini to
      produce active peptide SPR sensors that were tested for IgG binding. The dynamics
      and extent of peptide-IgG binding were compared with results from a conventional
      system using protein A attached on a gold surface via disulfide monolayers. IgG
      binding to protein A on disulfide monolayers yielded equilibrium dissociation
      constants of 1.4*10(-7)M. The corresponding dissociation constant value for the
      acetylated version of the peptide (Ac-HWRGWV) supported on alkanethiol SAM was
      5.8*10(-7)M and that for HWRGWV on the alkanethiol SAM (after de-protection of
      Fmoc-HWRGWVA) was 1.2*10(-6)M. Maximum IgG binding capacities, Qm of 6.7, 3.8,
      and 4.1mgm(-2) were determined for the protein A and the two forms of HWRGWV
      based biosensors, respectively. Real-time data for the kinetics of adsorption
      were used to determine the apparent rate constants for adsorption and desorption.
      The results were analyzed to understand the mechanism of IgG binding to the
      protein and peptide ligands. It was found that the peptide-IgG binding was
      reaction controlled, however the protein A-IgG binding mechanism was partially
      mass transfer (diffusion) controlled. The adsorption rate constants, ka, for the
      protein A ligand increased with decreasing concentration of analyte and the
      peptide ligand ka values was constant at different IgG concentrations and flow
      rates. 

PMID- 24686151
TI  - Timing of cord clamping in very preterm infants: more evidence is needed.
AB  - In December 2012, the American College of Obstetricians and Gynecologists
      published a Committee Opinion entitled "Timing of umbilical cord clamping after
      birth." It stated that "evidence exists to support delayed cord clamping in
      preterm infants, when feasible. The single most important benefit for preterm
      infants is the possibility for a nearly 50% reduction in IVH." However, the
      Committee Opinion added that the ideal timing of umbilical cord clamping has yet
      to be determined and recommended that large clinical trials be conducted in the
      most preterm infants. Published randomized controlled trials include <200 infants
      of <30 weeks' gestation, with assessments of neurodevelopmental outcome in less
      than one-half of the children. This is a major gap in the evidence. Without
      reliable data from randomized controlled trials that optimally include childhood
      follow-up evaluations, we will not know whether delayed cord clamping may do more
      overall harm than good. Ongoing trials of delayed cord clamping plan to report
      childhood outcomes in >2000 additional very preterm infants. Current
      recommendations may need to change when these results become available. Greater
      international collaboration could accelerate resolution of whether this promising
      intervention will improve disability-free survival in about 1 million infants who
      will be born very preterm globally each year. 

PMID- 24686152
TI  - Simultaneous cusp-sparing aortic root replacement and coarctectomy with total
      arch replacement from the midline incision.
AB  - Four cases of simultaneous surgery for aortic root aneurysm with aortic
      regurgitation and coarctation of the aorta were presented. Age at surgery ranged
      from 18 to 37 years and all were male. All had annuloaortic ectasia and
      dilatation of the ascending aorta, 3 had bicuspid aortic valve and 1 had acute
      localized aortic dissection. Preoperative grade of aortic regurgitation was
      trivial in 1, moderate in 2 and severe in 1. Three had aortic valve-sparing root
      replacement with reimplantation technique and 1 had plication of the sinotubular
      junction. All patients had total arch replacement, coarctectomy and orthogonal
      anastomosis to the descending aorta. Antegrade cerebral perfusion was used for
      brain protection. All patients survived and postoperative pressure difference
      between the upper and lower extremities disappeared. Postoperative aortogram was
      satisfactory. 

PMID- 24686153
TI  - Patency of the internal mammary arteries after removal of the Nuss bar: an
      initial report.
AB  - OBJECTIVES: Surgical correction of pectus excavatum (PE) has shifted to the
      modern minimally invasive Nuss procedure, which proved to be safe and effective.
      In order to restore the dented deformity, custom-curved metal bars provide
      continuous retrosternal pressure but cross the habitat of the internal mammary
      arteries (IMAs) directly affecting their patency. In this initial report, we
      sought to assess the patency of the IMAs in the first 6 patients who underwent
      Nuss bar removal in our department. METHODS: In 2010, we started to perform
      correction of PE using the Nuss bar technique. In 2013, observational analysis
      was performed on the first 6 patients who underwent removal of the Nuss bar.
      Computed tomography angiography (CTA) was performed in order to assess the
      patency of both IMAs directly after removal. RESULTS: In 4 (67%) patients, IMA
      patency was affected unilaterally (total obstruction or highly decreased flow
      pattern) corresponding with the lowest retrosternal side. CONCLUSIONS: According
      to our preliminary results, the oppressive force of Nuss bars interferes with IMA
      patency and thereby compromises future usability in coronary artery bypass
      grafting (CABG). We recommend that patients undergoing CABG following the Nuss
      procedure undergo preoperative evaluation of IMA patency. This study will be
      continued to include a larger number of patients including follow-up CTA one year
      after removal of the bar.

PMID- 24686154
TI  - Establishment of right ventricle-pulmonary artery continuity as the first-stage
      palliation in older infants with pulmonary atresia with ventricular septal defect
      may be preferable to use of an arterial shunt.
AB  - OBJECTIVES: Right ventricle-pulmonary artery (RV-PA) conduit and systemic-to
      pulmonary artery (S-PA) shunt in younger infants for the first-stage palliation
      with pulmonary atresia with ventricular septal defect (PAVSD) obtained good
      results. However, the pulmonary arteries (PA) grow slow in older infants
      undergoing an S-PA shunt. We compared the clinical outcomes of the two procedures
      in older infants with PAVSD. METHODS: A total of 48 patients with PAVSD underwent
      the first-stage palliative procedure between January 2010 and July 2012. Patients
      were divided into the RV-PA group and the S-PA group based on whether they had an
      RV-PA conduit (n = 24) or an S-PA shunt (n = 24). The early and late outcomes
      were compared between groups. RESULTS: There was no significant difference in in
      hospital mortality, mechanical ventilation time, paediatric intensive care unit
      stay and hospital stay between groups (all P > 0.05). The RV-PA conduits were
      associated with better PA growth compared with the S-PA shunts (P < 0.001). The
      RV-PA group had a higher rate of second-stage biventricular surgery compared with
      the S-PA group (P = 0.03). The early outcomes among different conduits of the RV
      PA conduit were not different (all P > 0.05). A positive correlation was found
      between the size of conduits and body weight (R(2) = 0.684, P < 0.001).
      CONCLUSIONS: In older infants with PAVSD who underwent the first-stage palliative
      procedure, early outcomes showed no difference between the RV-PA conduit group
      and the S-PA shunt group. The RV-PA conduits were associated with better growth
      of the PA and higher rates of second-stage biventricular repair. Autologous
      pericardium is a good choice for RV-PA conduits, and there is a correlation
      between body weight and size of conduit.

PMID- 24686155
TI  - Efficient production of mutant phytase (phyA-7) derived from Selenomonas
      ruminantium using recombinant Escherichia coli in pilot scale.
AB  - A mutant gene of rumen phytase (phyA-7) was cloned into pET23b(+) vector and
      expressed in the Escherichia coli BL21 under the control of the T7 promoter. The
      study of fermentation conditions includes the temperature impacts of mutant
      phytase expression, the effect of carbon supplements over induction stage, the
      inferences of acetic acid accumulation upon enzyme expression and the comparison
      of one-stage and two-stage operations in batch mode. The maximum value of phytase
      activity was reached 107.0 U mL(-1) at induction temperature of 30 degrees C.
      Yeast extract supplement demonstrated a significant increase on both protein
      concentration and phytase activity. The acetic acid (2 g L(-1)) presented in the
      modified synthetic medium demonstrated a significant decrease on expressed
      phytase activity. A two-stage batch operation enhanced the level of phytase
      activity from 306 to 1204 U mL(-1) in the 20 L of fermentation scale. An overall
      3.7-fold improvement in phytase yield (35,375.72-1,31,617.50 U g(-1) DCW) was
      achieved in the two-stage operation.

PMID- 24686156
TI  - Expression of a novel recombinant fusion protein BVN-Tbeta4 and its effects on
      diabetic wound healing.
AB  - A recombinant fusion protein BVN-Tbeta4 is successfully expressed in Escherichia
      coli, purified in the laboratory and applied onto the wounds of diabetic mice to
      investigate its effects on diabetic wound healing. Our results show that the
      recombinant protein BVN-Tbeta4 can promote diabetic wound healing in the murine
      model.

PMID- 24686157
TI  - Bronchoalveolar lavage (BAL) for research; obtaining adequate sample yield.
AB  - We describe a research technique for fiberoptic bronchoscopy with bronchoalveolar
      lavage (BAL) using manual hand held suction in order to remove nonadherent cells
      and lung lining fluid from the mucosal surface. In research environments, BAL
      allows sampling of innate (lung macrophage), cellular (B- and T- cells), and
      humoral (immunoglobulin) responses within the lung. BAL is internationally
      accepted for research purposes and since 1999 the technique has been performed in
      > 1,000 subjects in the UK and Malawi by our group. Our technique uses gentle
      hand-held suction of instilled fluid; this is designed to maximize BAL volume
      returned and apply minimum shear force on ciliated epithelia in order to preserve
      the structure and function of cells within the BAL fluid and to preserve
      viability to facilitate the growth of cells in ex vivo culture. The research
      technique therefore uses a larger volume instillate (typically in the order of
      200 ml) and employs manual suction to reduce cell damage. Patients are given
      local anesthetic, offered conscious sedation (midazolam), and tolerate the
      procedure well with minimal side effects. Verbal and written subject information
      improves tolerance and written informed consent is mandatory. Safety of the
      subject is paramount. Subjects are carefully selected using clear inclusion and
      exclusion criteria. This protocol includes a description of the potential risks,
      and the steps taken to mitigate them, a list of contraindications, pre- and post
      procedure checks, as well as precise bronchoscopy and laboratory techniques. 

PMID- 24686159
TI  - Locating Errors Through Networked Surveillance: A Multimethod Approach to Peer
      Assessment, Hazard Identification, and Prioritization of Patient Safety Efforts
      in Cardiac Surgery.
AB  - OBJECTIVES: The objectives were to develop a scientifically sound and feasible
      peer-to-peer assessment model that allows health-care organizations to evaluate
      patient safety in cardiovascular operating rooms and to establish safety
      priorities for improvement. METHODS: The locating errors through networked
      surveillance study was conducted to identify hazards in cardiac surgical care. A
      multidisciplinary team, composed of organizational sociology, organizational
      psychology, applied social psychology, clinical medicine, human factors
      engineering, and health services researchers, conducted the study. We used a
      transdisciplinary approach, which integrated the theories, concepts, and methods
      from each discipline, to develop comprehensive research methods. Multiple data
      collection was involved: focused literature review of cardiac surgery-related
      adverse events, retrospective analysis of cardiovascular events from a national
      database in the United Kingdom, and prospective peer assessment at 5 sites,
      involving survey assessments, structured interviews, direct observations, and
      contextual inquiries. A nominal group methodology, where one single group acts to
      problem solve and make decisions was used to review the data and develop a list
      of the top priority hazards. RESULTS: The top 6 priority hazard themes were as
      follows: safety culture, teamwork and communication, infection prevention,
      transitions of care, failure to adhere to practices or policies, and operating
      room layout and equipment. CONCLUSIONS: We integrated the theories and methods of
      a diverse group of researchers to identify a broad range of hazards and good
      clinical practices within the cardiovascular surgical operating room. Our
      findings were the basis for a plan to prioritize improvements in cardiac surgical
      care. These study methods allowed for the comprehensive assessment of a high-risk
      clinical setting that may translate to other clinical settings.

PMID- 24686160
TI  - Bicycle helmets are highly effective at preventing head injury during head
      impact: head-form accelerations and injury criteria for helmeted and unhelmeted
      impacts.
AB  - Cycling is a popular form of recreation and method of commuting with clear health
      benefits. However, cycling is not without risk. In Canada, cycling injuries are
      more common than in any other summer sport; and according to the US National
      Highway and Traffic Safety Administration, 52,000 cyclists were injured in the US
      in 2010. Head injuries account for approximately two-thirds of hospital
      admissions and three-quarters of fatal injuries among injured cyclists. In many
      jurisdictions and across all age levels, helmets have been adopted to mitigate
      risk of serious head injuries among cyclists and the majority of epidemiological
      literature suggests that helmets effectively reduce risk of injury. Critics have
      raised questions over the actual efficacy of helmets by pointing to weaknesses in
      existing helmet epidemiology including selection bias and lack of appropriate
      control for the type of impact sustained by the cyclist and the severity of the
      head impact. These criticisms demonstrate the difficulty in conducting
      epidemiology studies that will be regarded as definitive and the need for
      complementary biomechanical studies where confounding factors can be adequately
      controlled. In the bicycle helmet context, there is a paucity of biomechanical
      data comparing helmeted to unhelmeted head impacts and, to our knowledge, there
      is no data of this type available with contemporary helmets. In this research,
      our objective was to perform biomechanical testing of paired helmeted and
      unhelmeted head impacts using a validated anthropomorphic test headform and a
      range of drop heights between 0.5m and 3.0m, while measuring headform
      acceleration and Head Injury Criterion (HIC). In the 2m (6.3m/s) drops, the
      middle of our drop height range, the helmet reduced peak accelerations from 824g
      (unhelmeted) to 181g (helmeted) and HIC was reduced from 9667 (unhelmeted) to
      1250 (helmeted). At realistic impact speeds of 5.4m/s (1.5m drop) and 6.3m/s
      (2.0m drop), bicycle helmets changed the probability of severe brain injury from
      extremely likely (99.9% risk at both 5.4 and 6.3m/s) to unlikely (9.3% and 30.6%
      risk at 1.5m and 2.0m drops respectively). These biomechanical results for
      acceleration and HIC, and the corresponding results for reduced risk of severe
      brain injury show that contemporary bicycle helmets are highly effective at
      reducing head injury metrics and the risk for severe brain injury in head impacts
      characteristic of bicycle crashes. 

PMID- 24686158
TI  - The Testosterone Trials: Seven coordinated trials of testosterone treatment in
      elderly men.
AB  - Background The prevalence of low testosterone levels in men increases with age,
      as does the prevalence of decreased mobility, sexual function, self-perceived
      vitality, cognitive abilities, bone mineral density, and glucose tolerance, and
      of increased anemia and coronary artery disease. Similar changes occur in men who
      have low serum testosterone concentrations due to known pituitary or testicular
      disease, and testosterone treatment improves the abnormalities. Prior studies of
      the effect of testosterone treatment in elderly men, however, have produced
      equivocal results. Purpose To describe a coordinated set of clinical trials
      designed to avoid the pitfalls of prior studies and to determine definitively
      whether testosterone treatment of elderly men with low testosterone is
      efficacious in improving symptoms and objective measures of age-associated
      conditions. Methods We present the scientific and clinical rationale for the
      decisions made in the design of this set of trials. Results We designed The
      Testosterone Trials as a coordinated set of seven trials to determine if
      testosterone treatment of elderly men with low serum testosterone concentrations
      and symptoms and objective evidence of impaired mobility and/or diminished libido
      and/or reduced vitality would be efficacious in improving mobility (Physical
      Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality
      Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial),
      bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular
      Trial). The scientific advantages of this coordination were common eligibility
      criteria, common approaches to treatment and monitoring, and the ability to pool
      safety data. The logistical advantages were a single steering committee, data
      coordinating center and data and safety monitoring board, the same clinical trial
      sites, and the possibility of men participating in multiple trials. The major
      consideration in participant selection was setting the eligibility criterion for
      serum testosterone low enough to ensure that the men were unequivocally
      testosterone deficient, but not so low as to preclude sufficient enrollment or
      eventual generalizability of the results. The major considerations in choosing
      primary outcomes for each trial were identifying those of the highest clinical
      importance and identifying the minimum clinically important differences between
      treatment arms for sample size estimation. Potential limitations Setting the
      serum testosterone concentration sufficiently low to ensure that most men would
      be unequivocally testosterone deficient, as well as many other entry criteria,
      resulted in screening approximately 30 men in person to randomize one
      participant. Conclusion Designing The Testosterone Trials as a coordinated set of
      seven trials afforded many important scientific and logistical advantages but
      required an intensive recruitment and screening effort.

PMID- 24686161
TI  - Not just a rural occurrence: differences in agricultural equipment crash
      characteristics by rural-urban crash site and proximity to town.
AB  - PURPOSE: Although approximately one-third of agricultural equipment-related
      crashes occur near town, these crashes are thought to be a rural problem. This
      analysis examines differences between agricultural equipment-related crashes by
      their urban-rural distribution and distance from a town. METHODS: Agricultural
      equipment crashes were collected from nine Midwest Departments of Transportation
      (2005-2008). Crash zip code was assigned as urban or rural (large, small and
      isolated) using Rural-Urban Commuting Areas. Crash proximity to a town was
      estimated with ArcGIS. Multivariable logistic regression was used to estimate the
      odds of crashing in an urban versus rural zip codes and across rural gradients.
      ANOVA analysis estimated mean distance (miles) from a crash site to a town.
      FINDINGS: Over four years, 4444 crashes involved agricultural equipment. About
      30% of crashes occurred in urban zip codes. Urban crashes were more likely to be
      non-collisions (aOR=1.69[1.24-2.30]), involve >=2 vehicles (2 vehicles:
      aOR=1.58[1.14-2.20], 3+ vehicles: aOR=1.68[0.98-2.88]), occur in a town
      (aOR=2.06[1.73-2.45]) and within one mile of a town (aOR=1.65[1.40-1.95]) than
      rural crashes. The proportion of crashes within a town differed significantly
      across rural gradients (P<0.0001). Small rural crashes, compared to isolated
      rural crashes, were 1.98 (95%CI[1.28-3.06]) times more likely to be non
      collisions. The distance from the crash to town differed significantly by the
      urban-rural distribution (P<0.0001). CONCLUSIONS: Crashes with agricultural
      equipment are unexpectedly common in urban areas and near towns and cities.
      Education among all roadway users, increased visibility of agricultural equipment
      and the development of complete rural roads are needed to increase road safety
      and prevent agricultural equipment-related crashes.

PMID- 24686162
TI  - Behavior-based safety on construction sites: a case study.
AB  - This work presents the results of a case study and describes an important area
      within the field of construction safety management, namely behavior-based safety
      (BBS). This paper adopts and develops a management approach for safety
      improvements in construction site environments. A rigorous behavioral safety
      system and its intervention program was implemented and deployed on target
      construction sites. After taking a few weeks of safety behavior measurements, the
      project management team implemented the designed intervention and measurements
      were taken. Goal-setting sessions were arranged on-site with workers'
      participation to set realistic and attainable targets of performance. Safety
      performance measurements continued and the levels of performance and the targets
      were presented on feedback charts. Supervisors were asked to give workers
      recognition and praise when they acted safely or improved critical behaviors.
      Observers were requested to have discussions with workers, visit the site,
      distribute training materials to workers, and provide feedback to crews and
      display charts. They were required to talk to operatives in the presence of line
      managers. It was necessary to develop awareness and understanding of what was
      being measured. In the process, operatives learned how to act safely when
      conducting site tasks using the designed checklists. Current weekly scores were
      discussed in the weekly safety meetings and other operational site meetings with
      emphasis on how to achieve set targets. The reliability of the safety performance
      measures taken by the company's observers was monitored. A clear increase in
      safety performance level was achieved across all categories: personal protective
      equipment; housekeeping; access to heights; plant and equipment, and scaffolding.
      The research reveals that scores of safety performance at one project improved
      from 86% (at the end of 3rd week) to 92.9% during the 9th week. The results of
      intervention demonstrated large decreases in unsafe behaviors and significant
      increases in safe behaviors. The results of this case study showed that an
      approach based on goal setting, feedback, and an effective measure of safety
      behavior if properly applied by committed management, can improve safety
      performance significantly in construction site environments. The results proved
      that the BBS management technique can be applied to any country's culture,
      showing that it would be a good approach for improving the safety of front-line
      workers and that it has industry wide application for ongoing construction
      projects. 

PMID- 24686163
TI  - The influence of dispositional mindfulness on safety behaviors: a dual process
      perspective.
AB  - Based on the dual process model of human cognition, this study investigated the
      influence of dispositional mindfulness on operators' safety behaviors and its
      boundary conditions. In a sample of 212 nuclear power plant control room
      operators, it was found that both safety compliance and safety participation
      behaviors were positively influenced by dispositional mindfulness as measured by
      the 14-item Freiburg Mindfulness Inventory. This effect was still positive after
      controlling for age, intelligence, work experience and conscientiousness.
      Moreover, two boundary conditions were identified: the impact of dispositional
      mindfulness of safety behaviors was stronger among operators who were either more
      experienced or more intelligent. Theoretically, the framework we used to
      understand the benefit of mindfulness on safety behaviors has been proved to be
      useful. Practically, it provides a new and valid criterion that could be used in
      operators' selection and training program to improve organizational safety. 

PMID- 24686164
TI  - The impact of alcohol and road traffic policies on crash rates in Botswana, 2004
      2011: a time-series analysis.
AB  - In Botswana, increased development and motorization have brought increased road
      traffic-related death rates. Between 1981 and 2001, the road traffic-related
      death rate in Botswana more than tripled. The country has taken several steps
      over the last several years to address the growing burden of road traffic crashes
      and particularly to address the burden of alcohol-related crashes. This study
      examines the impact of the implementation of alcohol and road safety-related
      policies on crash rates, including overall crash rates, fatal crash rates, and
      single-vehicle nighttime fatal (SVNF) crash rates, in Botswana from 2004 to 2011.
      The overall crash rate declined significantly in June 2009 and June 2010, such
      that the overall crash rate from June 2010 to December 2011 was 22% lower than
      the overall crash rate from January 2004 to May 2009. Additionally, there were
      significant declines in average fatal crash and SVNF crash rates in early 2010.
      Botswana's recent crash rate reductions occurred during a time when aggressive
      policies and other activities (e.g., education, enforcement) were implemented to
      reduce alcohol consumption and improve road safety. While it is unclear which of
      the policies or activities contributed to these declines and to what extent,
      these reductions are likely the result of several, combined efforts. 

PMID- 24686165
TI  - The role of parents and non-parents in the supervision of learner drivers in
      Australia.
AB  - The purpose of this study was to contrast the role of parental and non-parental
      (sibling, other family and non-family) supervisors in the supervision of learner
      drivers in graduated driver licensing systems. The sample consisted of 522
      supervisors from the Australian states of Queensland (n=204, 39%) and New South
      Wales (n=318, 61%). The learner licence requirements in these two states are
      similar, although learners in Queensland are required to accrue 100h of
      supervision in a log book while those in New South Wales are required to accrue
      120h. Approximately 50 per cent of the sample (n=255) were parents of the learner
      driver while the remainder of the sample were either siblings (n=72, 13.8%),
      other family members (n=153, 29.3%) or non-family (n=114, 21.8%). Parents were
      more likely than siblings, other family or non-family members to be the primary
      supervisor of the learner driver. Siblings provided fewer hours of practice when
      compared with other supervisor types while the median and mode suggest that
      parents provided the most hours of practice to learner drivers. This study
      demonstrates that non-parental supervisors, such as siblings, other family
      members and non-family, at least in jurisdictions that require 100 or 120h of
      practice, are important in facilitating learner drivers to accumulate sufficient
      supervised driving practice. 

PMID- 24686166
TI  - Endothelial cell-secreted EGF induces epithelial to mesenchymal transition and
      endows head and neck cancer cells with stem-like phenotype.
AB  - Emerging evidence suggests that endothelial cell-secreted factors contribute to
      the pathobiology of squamous cell carcinoma (SCC) by enhancing invasive migration
      and resistance to anoikis. Here, we report that SCC cells within the perivascular
      niche have undergone epithelial to mesenchymal transition (EMT) in a primary
      human SCC of a patient that developed distant metastases. Endothelial cell
      secreted EGF induced EMT of human SCC cells in vitro and also induced acquisition
      of a stem-like phenotype. In vivo, tumor xenografts vascularized with EGF
      silenced endothelial cells exhibited a smaller fraction of cancer stem-like cells
      (ALDH(+)CD44(+)) and were less invasive than tumors vascularized with control
      endothelial cells. Collectively, these results demonstrated that endothelial cell
      EGF induces EMT and acquisition of stem-like properties by head and neck tumor
      cells. On this basis, we suggest that vascular endothelial cells contribute to
      tumor dissemination by secreting factors that endow carcinoma cells with enhanced
      motility and stemness.

PMID- 24686167
TI  - Endogenous two-photon fluorescence imaging elucidates metabolic changes related
      to enhanced glycolysis and glutamine consumption in precancerous epithelial
      tissues.
AB  - Alterations in the balance between different metabolic pathways used to meet
      cellular bioenergetic and biosynthetic demands are considered hallmarks of
      cancer. Optical imaging relying on endogenous fluorescence has been used as a
      noninvasive approach to assess tissue metabolic changes during cancer
      development. However, quantitative correlations of optical assessments with
      variations in the concentration of relevant metabolites or in the specific
      metabolic pathways that are involved have been lacking. In this study, we use
      high-resolution, depth-resolved imaging, relying entirely on endogenous two
      photon excited fluorescence in combination with invasive biochemical assays and
      mass spectrometry to demonstrate the sensitivity and quantitative nature of
      optical redox ratio tissue assessments. We identify significant differences in
      the optical redox ratio of live, engineered normal and precancerous squamous
      epithelial tissues. We establish that while decreases in the optical redox ratio
      are associated with enhanced levels of glycolysis relative to oxidative
      phosphorylation, increases in glutamine consumption to support energy production
      are associated with increased optical redox ratio values. Such mechanistic
      insights in the origins of optical metabolic assessments are critical for
      exploiting fully the potential of such noninvasive approaches to monitor and
      understand important metabolic changes that occur in live tissues at the onset of
      cancer or in response to treatment.

PMID- 24686168
TI  - Distinguishing between benign and malignant melanocytic nevi by in vivo
      multiphoton microscopy.
AB  - Monitoring of atypical nevi is an important step in early detection of melanoma,
      a clinical imperative in preventing the disease progression. Current standard
      diagnosis is based on biopsy and histopathologic examination, a method that is
      invasive and highly dependent upon physician experience. In this work, we used a
      clinical multiphoton microscope to image in vivo and noninvasively melanocytic
      nevi at three different stages: common nevi without dysplastic changes,
      dysplastic nevi with structural and architectural atypia, and melanoma. We
      analyzed multiphoton microscopy (MPM) images corresponding to 15 lesions (five in
      each group) both qualitatively and quantitatively. For the qualitative analysis,
      we identified the morphologic features characteristic of each group. MPM images
      corresponding to dysplastic nevi and melanoma were compared with standard
      histopathology to determine correlations between tissue constituents and
      morphology and to evaluate whether standard histopathology criteria can be
      identified in the MPM images. Prominent qualitative correlations included the
      morphology of epidermal keratinocytes, the appearance of nests of nevus cells
      surrounded by collagen fibers, and the structure of the epidermal-dermal
      junction. For the quantitative analysis, we defined a numerical multiphoton
      melanoma index (MMI) based on three-dimensional in vivo image analysis that
      scores signals derived from two-photon excited fluorescence, second harmonic
      generation, and melanocyte morphology features on a continuous 9-point scale.
      Indices corresponding to common nevi (0-1), dysplastic nevi (1-4), and melanoma
      (5-8) were significantly different (P < 0.05), suggesting the potential of the
      method to distinguish between melanocytic nevi in vivo.

PMID- 24686169
TI  - NF-kappaB gene signature predicts prostate cancer progression.
AB  - In many patients with prostate cancer, the cancer will be recurrent and
      eventually progress to lethal metastatic disease after primary treatment, such as
      surgery or radiation therapy. Therefore, it would be beneficial to better predict
      which patients with early-stage prostate cancer would progress or recur after
      primary definitive treatment. In addition, many studies indicate that activation
      of NF-kappaB signaling correlates with prostate cancer progression; however, the
      precise underlying mechanism is not fully understood. Our studies show that
      activation of NF-kappaB signaling via deletion of one allele of its inhibitor,
      IkappaBalpha, did not induce prostatic tumorigenesis in our mouse model. However,
      activation of NF-kappaB signaling did increase the rate of tumor progression in
      the Hi-Myc mouse prostate cancer model when compared with Hi-Myc alone. Using the
      nonmalignant NF-kappaB-activated androgen-depleted mouse prostate, a NF-kappaB
      activated recurrence predictor 21 (NARP21) gene signature was generated. The
      NARP21 signature successfully predicted disease-specific survival and distant
      metastases-free survival in patients with prostate cancer. This transgenic mouse
      model-derived gene signature provides a useful and unique molecular profile for
      human prostate cancer prognosis, which could be used on a prostatic biopsy to
      predict indolent versus aggressive behavior of the cancer after surgery.

PMID- 24686170
TI  - LEO1 is regulated by PRL-3 and mediates its oncogenic properties in acute
      myelogenous leukemia.
AB  - PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of
      acute myelogenous leukemia (AML) and associated with poor survival. We found that
      stable expression of PRL-3 confers cytokine independence and growth advantage of
      AML cells. However, how PRL-3 mediates these functions in AML is not known. To
      comprehensively screen for PRL3-regulated proteins in AML, we performed SILAC
      based quantitative proteomics analysis and discovered 398 significantly perturbed
      proteins after PRL-3 overexpression. We show that Leo1, a component of RNA
      polymerase II-associated factor (PAF) complex, is a novel and important mediator
      of PRL-3 oncogenic activities in AML. We described a novel mechanism where
      elevated PRL-3 protein increases JMJD2C histone demethylase occupancy on Leo1
      promoter, thereby reducing the H3K9me3 repressive signals and promoting Leo1 gene
      expression. Furthermore, PRL-3 and Leo1 levels were positively associated in AML
      patient samples (N=24; P<0.01). On the other hand, inhibition of Leo1 reverses
      PRL-3 oncogenic phenotypes in AML. Loss of Leo1 leads to destabilization of the
      PAF complex and downregulation of SOX2 and SOX4, potent oncogenes in myeloid
      transformation. In conclusion, we identify an important and novel mechanism by
      which PRL-3 mediates its oncogenic function in AML.

PMID- 24686171
TI  - Sphingosine kinase 2 promotes acute lymphoblastic leukemia by enhancing MYC
      expression.
AB  - Sphingosine kinase 2 (SK2) may have utility as a prognostic marker in
      inflammatory diseases such as cancer in which it has been rationalized as a
      candidate therapeutic target. Here, we show that SK2 has an oncogenic role in
      acute lymphoblastic leukemia (ALL) by influencing expression of MYC. Genetic
      ablation of SK2 impaired leukemia development in a mouse model of ALL and
      pharmacologic inhibition extended survival in mouse xenograft models of human
      disease. SK2 attenuation in both the settings reduced MYC expression in leukemic
      cells, with reduced levels of acetylated histone H3 within the MYC gene
      associated with reduced levels of MYC protein and expression of MYC-regulated
      genes. Our results demonstrated that SK2 regulates MYC, which has a pivotal role
      in hematologic malignancies, providing a preclinical proof of concept for this
      pathway as a broad-based therapeutic target in this setting.

PMID- 24686172
TI  - IGF-I regulates redox status in breast cancer cells by activating the amino acid
      transport molecule xC-.
AB  - Insulin-like growth factors (IGF) stimulate cell growth in part by increasing
      amino acid uptake. xCT (SLC7A11) encodes the functional subunit of the cell
      surface transport system xC(-), which mediates cystine uptake, a pivotal step in
      glutathione synthesis and cellular redox control. In this study, we show that IGF
      I regulates cystine uptake and cellular redox status by activating the expression
      and function of xCT in estrogen receptor-positive (ER(+)) breast cancer cells by
      a mechanism that relies on the IGF receptor substrate-1 (IRS-1). Breast cancer
      cell proliferation mediated by IGF-I was suppressed by attenuating xCT expression
      or blocking xCT activity with the pharmacologic inhibitor sulfasalazine (SASP).
      Notably, SASP sensitized breast cancer cells to inhibitors of the type I IGF
      receptor (IGF-IR) in a manner reversed by the reactive oxygen species (ROS)
      scavenger N-acetyl-L-cysteine. Thus, IGF-I promoted the proliferation of ER(+)
      breast cancer cells by regulating xC(-) transporter function to protect cancer
      cells from ROS in an IRS-1-dependent manner. Our findings suggest that inhibiting
      xC(-) transporter function may synergize with modalities that target the IGF-IR
      to heighten their therapeutic effects.

PMID- 24686174
TI  - E3 ubiquitin ligase HOIP attenuates apoptotic cell death induced by cisplatin.
AB  - The genotoxin cisplatin is commonly used in chemotherapy to treat solid tumors,
      yet our understanding of the mechanism underlying the drug response is limited.
      In a focused siRNA screen, using an siRNA library targeting genes involved in
      ubiquitin and ubiquitin-like signaling, we identified the E3 ubiquitin ligase
      HOIP as a key regulator of cisplatin-induced genotoxicity. HOIP forms, with
      SHARPIN and HOIL-1L, the linear ubiquitin assembly complex (LUBAC). We show that
      cells deficient in the HOIP ligase complex exhibit hypersensitivity to cisplatin.
      This is due to a dramatic increase in caspase-8/caspase-3-mediated apoptosis that
      is strictly dependent on ATM-, but not ATR-mediated DNA damage checkpoint
      activation. Moreover, basal and cisplatin-induced activity of the stress response
      kinase JNK is enhanced in HOIP-depleted cells and, conversely, JNK inhibition can
      increase cellular resistance to cisplatin and reverse the apoptotic
      hyperactivation in HOIP-depleted cells. Furthermore, we show that HOIP depletion
      sensitizes cancer cells, derived from carcinomas of various origins, through an
      enhanced apoptotic cell death response. We also provide evidence that ovarian
      cancer cells classified as cisplatin-resistant can regain sensitivity following
      HOIP downregulation. Cumulatively, our study identifies a HOIP-regulated
      antiapoptotic signaling pathway, and we envisage HOIP as a potential target for
      the development of combinatorial chemotherapies to potentiate the efficacy of
      platinum-based anticancer drugs.

PMID- 24686175
TI  - Distinct role of tumor necrosis factor receptor subtypes 1 and 2 in the red
      nucleus in the development of neuropathic pain.
AB  - Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha)
      in the red nucleus (RN) plays a facilitated role in the development of
      neuropathic pain. Here, the protein levels and roles of two different TNF
      receptors, p55 type 1 (TNFR1) and p75 type 2 (TNFR2), in the RN of rats with
      spared nerve injury (SNI) were investigated. Immunohistochemistry demonstrated
      that both TNFR1 and TNFR2 were significantly increased in the RN of rats with SNI
      compared with sham-operated and normal rats. The up-regulation of TNFR1 occurred
      at two weeks after SNI, while TNFR2 had markedly increased already at one week
      and began to decrease at two weeks after SNI. Microinjection of different doses
      (500, 250 and 100ng) of anti-TNFR1 antibody (anti-TNFR1-Ab) or anti-TNFR2-Ab into
      the RN contralateral to the nerve injury side dose-dependently increased the paw
      withdrawal threshold of rats, as assessed using von Frey filaments. The analgesic
      effects produced by anti-TNFR1-Ab at one week and two weeks after SNI did not
      show significant difference. However, the analgesic effect produced by anti-TNFR2
      Ab at two weeks after SNI was significantly lower and shorter than that produced
      at one week after SNI. Combined injection of anti-TNFR1-Ab and anti-TNFR2-Ab
      (500ng for each antibody) into the RN generated a relatively faster and longer
      analgesic effect compared with single using of anti-TNFR1-Ab or anti-TNFR2-Ab.
      These results support that TNF-alpha in the RN plays a crucial role in regulating
      neuropathic pain, and suggest that the algesic effect of TNF-alpha is transmitted
      through both TNFR1 and TNFR2. TNFR1 has equally important role in the early
      development and later maintenance of neuropathic pain, while TNFR2 is more
      inclined to play a role in the early development of neuropathic pain. 

PMID- 24686176
TI  - Oscillations in a neurite growth model with extracellular feedback.
AB  - We consider the influence of extracellular signalling on neurite elongation in a
      model of neurite growth mediated by building proteins (e.g., tubulin). The
      tubulin production dynamics were supplied by a function describing the influence
      of extracellular signalling, which can promote or depress neurite elongation. We
      found that this extracellular feedback could generate neurite length oscillations
      consisting of a periodic sequence of elongations and retractions. The
      oscillations prevent further outgrowth of the neurite, which becomes trapped in
      the non-uniform extracellular field. We analysed the characteristics of the
      elongation process for different distributions of attracting and repelling
      sources of the extracellular signalling molecules. The model predicts three
      different scenarios of neurite development in the extracellular field, including
      monotonic and oscillatory outgrowth, localised limit cycle oscillations and
      complete growth depression. 

PMID- 24686178
TI  - Mitogen-activated protein kinase phosphatase 1 negatively regulates MAPK
      signaling in mouse hypothalamus.
AB  - Mitogen-activated protein kinase phosphatase 1 (MKP-1) is shown to negatively
      regulate MAPK signaling in various peripheral tissues as well as the central
      nervous system such as cortex, striatum and hippocampus. In this study, we
      examined whether MKP-1 regulates MAPK signaling in the mouse hypothalamus.
      Intraperitoneal injection of TNFalpha significantly increased MKP-1 mRNA
      expression in paraventricular and arcuate nuclei in the hypothalamus. TNFalpha
      treatment induced increases in MKP-1 expression at both mRNA and protein levels,
      accompanied by the inactivation of MAPK signaling in mouse hypothalamic explants.
      Inhibition of MKP-1 by its inhibitor or siRNA increased MAPK activity in the
      explants. Our data indicate that MKP-1 negatively regulates MAPK signaling in the
      mouse hypothalamus. 

PMID- 24686177
TI  - Differential effects of dorsal hippocampal inactivation on expression of recent
      and remote drug and fear memory.
AB  - Drugs of abuse generate strong drug-context associations, which can evoke
      powerful drug cravings that are linked to reinstatement in animal models and to
      relapse in humans. Work in learning and memory has demonstrated that contextual
      memories become more distributed over time, shifting from dependence on the
      hippocampus for retrieval to dependence on cortical structures. Implications for
      such changes in the structure of memory retrieval to addiction are unknown. Thus,
      to determine if the passage of time alters the substrates of conditioned place
      preference (CPP) memory retrieval, we investigated the effects of inactivation of
      the dorsal hippocampus (DH) with the GABA-A receptor agonist muscimol on
      expression of recent or remote CPP. We compared these effects with the same
      manipulation on expression of contextual fear conditioning. DH inactivation
      produced similar deficits in expression of both recent and remote CPP, but
      blocked expression of recent but not remote contextual fear memory. We describe
      the implications of these findings for mechanisms underlying long-term storage of
      contextual information. 

PMID- 24686179
TI  - Myelinated Ah-type trigeminal ganglion neurons in female rats: neuroexcitability,
      chemosensitivity to histamine, and potential clinical impact.
AB  - Migraine is a chronic neurological disorder characterized by recurrent moderate
      to-severe headaches often associated with numerous autonomic nervous system
      symptoms, and it is more prevalent in women. To fully understand the underlying
      mechanism, standard electrophysiology was performed with trigeminal ganglion
      neurons (TGNs) isolated from adult rats of both genders using the whole-cell
      patch clamp technique to test the distribution, neuroexcitability, and
      chemosensitivity to histamine. In addition to traditionally classified A- and C
      type TGNs, myelinated Ah-type TGNs were also observed in females. The
      electrophysiological features showed low firing threshold and the capability to
      fire repetitively upon stimulation. Ah-type neurons also functionally expressed
      persistent TTX-R Na(+) channels with more hyperpolarized activating voltage.
      Iberiotoxin and NS11021 significantly altered the discharge profiles of Ah-type
      TGNs. Finally, Ah-type TGNs showed a more potent reaction to histamine, with
      relatively larger inward currents and membrane depolarization compared with C
      types. These data provide evidence of the gender-specific distribution of
      myelinated Ah-type TGNs in adult female rats, characterized by a low threshold
      and high frequency of firing that are at least partially attributable to
      persistent TTX-R Na(+) and BK-KCa channel expression and potent chemosensitivity
      to histamine, suggesting that Ah-type TGNs may play a key role in gender
      differences in migraine.

PMID- 24686180
TI  - Expression analysis of the genes identified in GWAS of the postmortem brain
      tissues from patients with schizophrenia.
AB  - Many gene expression studies have examined postmortem brain tissues of patients
      with schizophrenia. However, only a few expression studies of the genes
      identified in genome-wide association study (GWAS) have been published to date.
      We measured the expression levels of the genes identified in GWAS (ZNF804A,
      OPCML, RPGRIP1L, NRGN, and TCF4) of the postmortem brain tissues of patients with
      schizophrenia and controls from two separate sample sets (i.e., the Australian
      Tissue Resource Center and Stanley Medical Research Institute). We also
      determined whether the single-nucleotide polymorphisms (SNPs) identified in the
      GWAS were related to the gene expression changes in the prefrontal cortex. No
      difference was observed between the patients with schizophrenia and controls from
      the Australian Tissue Resource Center samples in the mRNA levels of ZNF804A,
      OPCML, RPGRIP1L, NRGN, or TCF4. The lack of mRNA change for these five
      transcripts was also found in the brain samples from the Stanley Medical Research
      Institute. In addition, no relationship between the schizophrenia-associated SNPs
      identified in the GWAS and the corresponding gene expression was observed in
      either sample set. Our results suggest that major changes in the transcript
      levels of the five candidate genes identified in the GWAS may not occur in adult
      patients with schizophrenia. The lack of linkage between the risk gene
      polymorphisms and the expression levels of their major transcripts suggests that
      the control of pan mRNA levels may not be a prominent mechanism by which the
      genes identified in the GWAS contribute to the pathophysiology of schizophrenia.
      Further studies are needed to examine how the genes identified in the GWAS
      contribute to the pathophysiology of schizophrenia. 

PMID- 24686181
TI  - The progestin etonogestrel enhances the respiratory response to metabolic
      acidosis in newborn rats. Evidence for a mechanism involving supramedullary
      structures.
AB  - Central congenital hypoventilation syndrome is a neuro-respiratory disease
      characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the
      retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+)
      chemosensitivity has been observed in some central congenital hypoventilation
      syndrome patients coincidental with contraceptive treatment by a potent
      progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin
      effect remain unknown, although structures of medulla oblongata, midbrain or
      diencephalon are known to be targets for progesterone. In the present study, on
      ex vivo preparations of central nervous system of newborn rats, we show that
      acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the
      increased respiratory frequency induced by metabolic acidosis via a mechanism
      involving supramedullary structures located in pontine, mesencephalic or
      diencephalic regions.

PMID- 24686182
TI  - Apelin-13 protects the brain against ischemia/reperfusion injury through
      activating PI3K/Akt and ERK1/2 signaling pathways.
AB  - Apelin has been proved to protect the heart against ischemia/reperfusion (I/R)
      injury via the activation of phosphatidylinositol 3-kinase (PI3K)/Akt and
      extracellular signal-regulated kinase (ERK) signaling pathways. Whether this
      protective effect applies to brain I/R injury needed to be explored. We therefore
      investigated the potential neuroprotective role of Apelin-13 and the underlying
      mechanisms. Focal transient cerebral I/R model in male ICR mice was induced by
      60min of ischemia followed by reperfusion. Apelin-13 intracerebroventricular
      injection was performed 15 min before reperfusion. Neurological function, infarct
      volume, brain edema and apoptosis were measured at 24h after stroke. To further
      test the mechanism of Apelin-13, PI3K inhibitor LY294002 and ERK1/2 inhibitor
      PD98059 were injected into the lateral cerebral ventricle 15min before ischemia.
      Compared with the Vehicle group, Apelin-13 significantly ameliorated neurological
      deficit, infarct volume, brain edema and reduced TUNEL-positive cells. Bax,
      caspase-3 and cleaved caspase-3 were down-regulated and Bcl-2 up-regulated.
      While, the effect of Apelin-13 on Bax, Bcl-2, caspase-3 and cleaved caspase-3 was
      attenuated by LY294002 and PD98059. Apelin protected the brain against I/R insult
      injury, and this effect may be through activation of PI3K/Akt and ERK1/2
      signaling pathways.

PMID- 24686183
TI  - Expression of the JAK/STAT3/SOCS3 signaling pathway in herniated lumbar discs.
AB  - The inflammatory cytokine interleukin-6 (IL-6) plays an important role in causing
      symptoms of lumbar disk herniation. The present study clarifies the expression of
      the signaling pathway of IL-6 in herniated discs. Homogenates prepared from
      lumbar herniated discs from 10 patients were assessed. The expression of janus
      kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3),
      phosphorylated (p)-STAT3 at Tyr(705), suppressor of cytokine signaling 3 (SOCS3)
      and actin was examined by Western blot analysis. The expression of JAK1, STAT3,
      and p-STAT3 at Tyr(705) was also examined by immunostaining. JAK1, STAT3, p-STAT3
      at Tyr(705) and SOCS3 were detected in almost all cases. Immunoreactivity against
      JAK1 and STAT3 was observed mainly in chondrocytes, whereas immunoreactivity
      against p-STAT3 at Tyr(705) was observed in the nuclei of chondrocytes. The
      JAK/STAT signaling pathway might be activated by IL-6 and transmit messages from
      the cell surface to the nucleus, and the pathway is negatively regulated by
      SOCS3. These JAK1, STAT3 and SOCS3 molecules might tightly regulate and play a
      role in the degeneration of chondrocytes within herniated discs. 

PMID- 24686184
TI  - Applying anodal tDCS during tango dancing in a patient with Parkinson's disease.
AB  - Gait disturbance in patients with Parkinson's disease remains a therapeutic
      challenge, given its poor response to levodopa. Dance therapy is of recognised
      benefit in these patients, particularly partnered dance forms such as the tango.
      In parallel, non-invasive brain stimulation has begun to show promise for the
      rehabilitation of patients with Parkinson's disease, although effects on gait,
      compared to upper limbs, have been less well defined. We applied transcranial
      direct current stimulation (tDCS) in a 79 year old male patient with moderate
      Parkinson's disease during tango dancing to assess its effect on trunk motion and
      balance. The patient performed a total of four dances over two days, two
      'tango+tDCS' and two 'tango+sham' in a randomised double-blind fashion. In a
      separate experimental session we also assessed the isolated effect of tDCS (and
      sham) on gait without tango dancing. For the dance session, trunk peak velocity
      during tango was significantly greater during tDCS compared to sham stimulation.
      In the gait experiments we observed a modest but significant reduction in the
      time taken to complete the 3m 'timed up and go' and 6m walk, and an increase in
      overall gait velocity and peak pitch trunk velocity with tDCS compared to sham.
      Our findings suggest that tDCS may be a useful adjunct to gait rehabilitation for
      patients with PD, although studies in a larger group of patients are needed to
      evaluate the therapeutic use of non-invasive brain stimulation during dance
      therapy. 

PMID- 24686185
TI  - Satellite glial cells in dorsal root ganglia are activated in experimental
      autoimmune encephalomyelitis.
AB  - Pain is a serious and common problem with patients suffering from multiple
      sclerosis (MS). Very little has been done to investigate the peripheral
      mechanisms of pain in MS. Here we used a mouse model of experimental autoimmune
      encephalomyelitis (EAE) to investigate the possible contribution of satellite
      glial cells (SGCs) to pain in MS. EAE mice had reduced pain thresholds 10 days
      after disease induction. We examined dorsal root ganglia and found increased
      expression of glial fibrillary acidic protein in SGCs, a marker of SGC
      activation, and increased coupling among SGCs, a known component of activated
      SGCs. Activated SGCs have previously been shown to contribute to pain in other
      classical neuropathic pain models, suggesting that pain in multiple sclerosis has
      a peripheral component. 

PMID- 24686186
TI  - Changes in ascorbate, glutathione and alpha-tocopherol concentrations in the
      brain regions during normal development and moderate hypoglycemia in rats.
AB  - Ascorbate, glutathione and alpha-tocopherol are the major low molecular weight
      antioxidants in the brain. The simultaneous changes in these compounds during
      normal development, and under a pro-oxidant condition are poorly understood.
      Ascorbate, glutathione and alpha-tocopherol concentrations in the olfactory bulb,
      cerebral cortex, hippocampus, striatum, hypothalamus, midbrain, cerebellum, pons
      and medulla oblongata were determined in postnatal day (P) 7, P14 and P60 male
      rats. A separate group of P14 and P60 rats were subjected to acute hypoglycemia,
      a pro-oxidant condition, prior to tissue collection. The concentrations of all
      three antioxidants were 100-600% higher in the brain regions at P7 and P14,
      relative to P60. The neuron-rich anterior brain regions (cerebral cortex and
      hippocampus) had higher concentrations of all three antioxidants than the myelin
      rich posterior regions (pons and medulla oblongata) at P14 and P60. Hypoglycemia
      had a differential effect on the antioxidants. Glutathione was decreased at both
      P14 and P60. However, the decrease was localized at P14 and global at P60.
      Hypoglycemia had no effect on ascorbate and alpha-tocopherol at either age.
      Higher antioxidant concentrations in the developing brain may reflect the risk of
      oxidant stress during the early postnatal period and explain the relative
      resistance to oxidant-mediated injury at this age. 

PMID- 24686188
TI  - Association of seven functional polymorphisms of one-carbon metabolic pathway
      with total plasma homocysteine levels and susceptibility to Parkinson's disease
      among South Indians.
AB  - This study from South India was performed to ascertain the impact of seven
      functional polymorphisms of one-carbon metabolic pathway on total plasma
      homocysteine levels and susceptibility to PD. A total of 151 cases of Parkinson's
      disease and 416 healthy controls were analyzed for fasting plasma homocysteine
      levels by reverse phase HPLC. PCR-RFLP approaches were used to analyze glutamate
      carboxypeptidase II (GCPII) 1561 C>T, reduced folate carrier 1 (RFC1) 80 G>A,
      cytosolic serine hydroxymethyl transferase (cSHMT) 1420 C>T, methylene
      tetrahydrofolate reductase (MTHFR) 677 C>T, methionine synthase (MTR) 2756 A>G
      and methionine synthase reductase (MTRR) 66 A>G polymorphisms. PCR-AFLP was used
      for the analysis of thymidylate synthase (TYMS) 5'-UTR 28bp tandem repeat. PD
      cases exhibited elevated plasma homocysteine levels compared to controls (men:
      28.8 +/- 6.9 vs. 16.4 +/- 8.8 MUmol/L; women: 25.4 +/- 5.3 vs. 11.2 +/-
      5.1MUmol/L). Homocysteine levels showed positive correlation with male gender
      (r=0.39, p<0.0001) and MTRR 66 A>G (r=0.31, p<0.0001) whereas an inverse
      correlation was observed with cSHMT 1420 C>T polymorphism. MTRR 66 A>G
      polymorphism showed independent risk for PD (OR: 3.42, 95% CI: 2.35-4.98) whereas
      cSHMT 1420 C>T conferred protection against PD (OR: 0.11, 95% CI: 0.07-0.17).
      Multifactor dimensionality reduction analysis showed synergistic interactions
      between MTHFR 677 C>T and MTRR 66 A>G, whereas cSHMT 1420 C>T exhibited
      counteracting interactions in altering susceptibility to PD. To conclude, PD
      cases exhibited hyperhomocysteinemia and MTRR 66 A>G and cSHMT 1420 C>T gene
      variants were shown to modulate PD risk by altering the homocysteine levels.

PMID- 24686187
TI  - The analgesia effect of duloxetine on post-operative pain via intrathecal or
      intraperitoneal administration.
AB  - One promising strategy to prevent the chronicity of post-operative pain (POP) is
      to attenuate acute POP during the early phase by efficacious medications with
      fewer side effects. Duloxetine, one of the serotonin (5-HT)-norepinephrine (NE)
      reuptake inhibitors (SNRI), is used to treat a wide range of acute and chronic
      pain. However, its effect on POP has not been investigated. In the present study,
      we investigated the anti-hypersensitivity effect of duloxetine using a rat model
      of POP. The possible involvement of spinal 5-HT2A and alpha2-noradrenergic
      receptors were also evaluated by using antagonists for 5-HT2A (ketanserin) or
      alpha2-noradrenergic receptors (idazoxan). Finally, with the method of in vivo
      microdialysis, the increase in spinal NA and 5-HT levels after intraperitoneal
      (i.p.) delivery of duloxetine were investigated. The results showed that
      intrathecal (i.t.) or i.p. delivery of duloxetine produced an anti-hyperalgesic
      effect in a dose-dependent manner. The anti-hypersensitivity effect of duloxetine
      was partly attenuated by pretreatment with ketanserin or idazoxane. Microdialysis
      study revealed that 5-HT and NA concentrations at the spinal dorsal horn were
      increased, peaking at 30min after i.p. injection of 20mg/kg duloxetine. These
      findings indicate that duloxetine inhibits POP by increasing spinal NA and 5-HT
      levels and activating spinal 5-HT2A or alpha2-noradrenergic receptors. 

PMID- 24686189
TI  - Postural sway and perceived comfort in pointing tasks.
AB  - In this study, we explored relations between indices of postural sway and
      perceived comfort during pointing postures performed by standing participants.
      The participants stood on a force plate, grasped a pointer with the dominant
      (right) hand, and pointed to targets located at four positions and at two
      distances from the body. We quantified postural sway over 60-s intervals at each
      pointing posture, and found no effects of target location or distance on postural
      sway indices. In contrast, comfort ratings correlated significantly with indices
      of one of the sway components, trembling. Our observations support the hypothesis
      that rambling and trembling sway components involve different neurophysiological
      mechanisms. They also suggest that subjective perception of comfort may be more
      important than the actual posture for postural sway. 

PMID- 24686190
TI  - Upregulation of glutamatergic transmission in anterior cingulate cortex in the
      diabetic rats with neuropathic pain.
AB  - Peripheral neuropathic pain is a common complication in the diabetic patients,
      and the underlying central mechanism remains unclear. Forebrain anterior
      cingulate cortex (ACC) is critically involved in the supraspinal perception of
      physical and affective components of noxious stimulus and pain modulation.
      Excitatory glutamatergic transmission in the ACC extensively contributed to the
      maintenance of negative affective component of chronic pain. The present study
      examined the adaptation of glutamatergic transmission in the ACC in rats with
      diabetic neuropathic pain. Injection with streptozotocin (STZ) induced
      hyperglycemia, thermal hyperalgesia and mechanical allodynia in the rats. In
      these rats, significant enhanced basal glutamatergic transmission was observed in
      the ACC neurons. The increased presynaptic glutamate release and enhanced
      conductance of postsynaptic glutamate receptors were also observed in the ACC
      neurons of these modeled rats. Increased phosphorylation of PKMzeta, but not the
      expression of total PKMzeta, was also observed in the ACC. Microinjection of
      PKMzeta inhibitor ZIP into ACC attenuated the upregulation of glutamate
      transmission and painful behaviors in STZ-injected rats. These results revealed a
      substantial central sensitization in the ACC neurons in the rodents with diabetic
      neuropathic pain, which may partially underlie the negative affective components
      of patients with diabetic neuropathic pain. 

PMID- 24686191
TI  - Nitric oxide stimulates glutamatergic synaptic inputs to baroreceptor neurons
      through potentiation of Cav2.2-mediated Ca(2+) currents.
AB  - Nitric oxide (NO) increases glutamate release to the second-order neurons in the
      nucleus tractus solitarius (NTS). N-type Ca(2+) channel is essential for
      triggering glutamate release at synaptic terminals. In this study, we determined
      the role of Cav2.2 subunit in NO-induced increase in glutamate synaptic inputs to
      NTS neurons. The second-order NTS neurons and nodose ganglionic (NG) neurons were
      identified by applying DiA, a fluorescent lipophilic tracer, on aortic depressor
      nerve in rats. NO donor DEA/NO significantly increased tractus solitarius (TS)
      evoked excitatory postsynaptic currents (EPSCs) in second-order NTS neurons, an
      effect was abolished by pretreatment of slice with ODQ, an inhibitor for soluble
      isoform of guanylyl cyclase. DEA/NO decreased the paired-pulse ratio of TS-evoked
      EPSCs, while increased the frequency, but not the amplitude, of miniature EPSCs
      in second-order NTS neurons. Furthermore, DEA/NO significantly increased Ba(2+)
      currents in identified baroreceptor NG neurons. However, DEA/NO had little effect
      on the Ba(2+) currents in the presence of specific N-type Ca(2+) blocker omega
      conotoxin GVIA. In addition, immunocytochemistry staining revealed that Cav2.2
      subunit immunoreactivates were colocalized with DiA-labeled baroreceptor nerve
      terminals in the NTS. Collectively, these findings suggest that NO stimulates
      glutamatergic synaptic inputs to second-order NTS neurons through augmentation of
      Cav2.2-mediated N-type Ca(2+) currents.

PMID- 24686193
TI  - Parathyroid hormone and heart rate variability in haemodialysis patients.
AB  - BACKGROUND: Depressed heart rate variability (HRV) reflects abnormal cardiac
      autonomic regulation and has been linked with increased cardiovascular risk and
      sudden cardiac death. High parathyroid hormone (PTH) levels have also been
      associated with an increased risk of sudden cardiac death in haemodialysis (HD)
      patients. Our aim was to investigate the association between HRV indices and PTH
      in HD patients. METHODS: Continuous intradialytic electrocardiograms were
      repeated in stable HD patients 5 times every 2 weeks. The absolute values of high
      frequency (HF) and low-frequency (LF) HRV components were calculated every 5 min
      and averaged during the first and last hour of each recording (distinguished by
      subscripts F and L, respectively). Pre-HD PTH, corrected calcium, and phosphate
      levels were measured before the first recording. RESULTS: Data were analysed for
      75 subjects aged 60 +/- 15, 32% females, 37% diabetics. Baseline biochemical
      parameters were PTH 44 +/- 32 pmol/l, calcium 2.3 +/- 0.2 mmol/l, and phosphate
      1.6 +/- 0.4 mmol/l. All HRV indices showed intra-subject stability over the 5
      recordings. Diabetics had lower LFL compared to non-diabetics (-5.5 +/- 0.5 vs. 
      5.2 +/- 0.5 after logarithmic transformation, p = 0.012). In non-diabetics, PTH
      correlated negatively with LFL and HFL (LFL r = -0.340, p = 0.020, HFL r = 
      0.325, p = 0.026) and phosphate correlated negatively with LFF (r = -0.427, p =
      0.003), HFF (r = -0.442, p = 0.002) and HFL (r = -0.307, p = 0.040). CONCLUSION:
      High PTH and phosphate are associated with depressed HRV in non-diabetic dialysis
      patients. Prospective studies are needed to evaluate the role of mineral
      abnormalities in autonomic imbalance and arrhythmic risk in HD patients.

PMID- 24686192
TI  - Effect of age and calorie restriction on corpus callosal integrity in rhesus
      macaques: a fiber tractography study.
AB  - The rhesus macaque exhibits age-related brain changes similar to humans, making
      an excellent model of normal aging. Calorie restriction is a dietary intervention
      that reduces age-related comorbidities in short-lived animals, and its effects
      are still under study in rhesus macaques. Here, using deterministic fiber
      tracking method, we examined the effects of age and calorie restriction on a
      diffusion tensor imaging measure of white matter integrity, fractional anisotropy
      (FA), within white matter tracks traversing the anterior (genu) and posterior
      (splenium) corpus callosum in rhesus monkeys. Our results show: (1) a significant
      inverse relationship between age and mean FA of tracks traversing the genu and
      splenium; (2) higher mean FA of the splenium tracks as compared to that of genu
      tracks across groups; and (3) no significant diet effect on mean track FA through
      either location. These results are congruent with the age-related decline in
      white matter integrity reported in humans and monkeys, and the anterior-to
      posterior gradient in white matter vulnerability to normal aging in humans.
      Further studies are warranted to critically evaluate the effect of calorie
      restriction on brain aging in this unique cohort of elderly primates. 

PMID- 24686194
TI  - Blood-brain barrier models and their relevance for a successful development of
      CNS drug delivery systems: a review.
AB  - During the research and development of new drugs directed at the central nervous
      system, there is a considerable attrition rate caused by their hampered access to
      the brain by the blood-brain barrier. Throughout the years, several in vitro
      models have been developed in an attempt to mimic critical functionalities of the
      blood-brain barrier and reliably predict the permeability of drug candidates.
      However, the current challenge lies in developing a model that retains
      fundamental blood-brain barrier characteristics and simultaneously remains
      compatible with the high throughput demands of pharmaceutical industries. This
      review firstly describes the roles of all elements of the neurovascular unit and
      their influence on drug brain penetration. In vitro models, including non-cell
      based and cell-based models, and in vivo models are herein presented, with a
      particular emphasis on their methodological aspects. Lastly, their contribution
      to the improvement of brain drug delivery strategies and drug transport across
      the blood-brain barrier is also discussed. 

PMID- 24686195
TI  - Evaluating heterogeneity of primary tumor (18)F-FDG uptake in breast cancer with
      a dedicated breast PET (MAMMI): a feasibility study based on correlation with
      PET/CT.
AB  - PURPOSE: The aim of the study was to evaluate the heterogeneity of primary tumor
      F-fluorodeoxyglucose ((18)F-FDG) uptake in breast cancer patients using a
      dedicated breast PET. PATIENTS AND METHODS: A positron emission
      tomography/computed tomography (PET/CT) of the thorax was performed 60 min after
      administration of 180-240 MBq of (18)F-FDG in patients with breast cancer.
      Subsequently, 110 min after injection, a scan was taken with a dedicated high
      resolution breast PET [MAMmography with Molecular Imaging (MAMMI)]. Both
      procedures were performed with the patients in the prone position. Four-point
      scores were used to compare the intensity (0: none; 1: mild; 2: moderate; 3:
      high) and heterogeneity (0: none; 1: mild; 2: moderate; 3: high) of (18)F-FDG
      uptake between PET/CT and MAMMI images. RESULTS: Thirty-five patients in whom the
      primary tumor was visualized on both scans were included in this analysis. The
      mean primary tumor size was 35.1 mm (range 10-108 mm). The mean intensity score
      was similar on both devices (2.4 for PET/CT and 2.3 for MAMMI; P=0.439), but the
      mean heterogeneity score on MAMMI images was significantly higher (PET/CT 1.9 vs.
      MAMMI 2.3; P=0.005). MAMMI showed a higher heterogeneity score in 11 (31%) of 35
      patients, especially in tumors with moderate or high intensity. Significantly
      higher heterogeneity scores on both PET/CT and MAMMI were seen in large tumors
      (P=0.005 and 0.014, respectively) and in tumors with high intensity scores
      (P=0.012 and P<0.001, respectively). CONCLUSION: Heterogeneous tumor (18)F-FDG
      uptake in breast cancer is frequently observed, particularly in large tumors with
      intense (18)F-FDG uptake. It is more often seen on MAMMI PET than on conventional
      PET/CT. Although the observed heterogeneity should be proven histopathologically,
      this finding offers a rationale for (18)F-FDG-guided biopsies.

PMID- 24686196
TI  - Rank classification based on the combination of indocyanine green retention rate
      at 15 min and (99m)Tc-DTPA-galactosyl human serum albumin scintigraphy predicts
      the safety of hepatic resection.
AB  - OBJECTIVES: (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is helpful
      in estimating liver function and the extent of liver fibrosis. Estimation of the
      liver function necessary for evaluating hepatic resection damage may be difficult
      in patients with chronic liver damage because of the discrepancy between liver
      functional parameters. The aim of this study was to develop a classification
      system for liver function using indocyanine green retention rate at 15 min (ICG
      R15) and the ratio of uptake by the liver to that by the liver and the heart at
      15 min (LHL15) in GSA scintigraphy for hepatic resection. METHODS: A total of 548
      consecutive patients who underwent hepatectomy were enrolled in this study. On
      the basis of ICG R15 cutoff values, the corresponding LHL15 values were
      determined for rank classification. Postoperative outcomes were compared between
      patients who met the classification and those who did not. RESULTS: Ranks were
      classified into four categories (rank, ICG R15 range, LHL15 range, minimum
      percentage of future liver remnant volume) - rank 1: <=10%, >=0.935, >35%; rank
      2: <=20%, >=0.90, >60%; rank 3: <=30%, >=0.87, >80%; and rank 4: >30%, <0.87,
      >90%. Patients meeting each classification showed significantly better morbidity,
      mortality, postoperative prothrombin time (PT) activity, and total bilirubin
      value on day 5 compared with those who did not. In the ICG rank 2 group (n=249),
      patients with LHL rank 4 had significantly worse platelet count, PT activity, and
      histological fibrosis than those with LHL rank 1 despite similar ICG R15 values.
      CONCLUSION: Rank classification can predict the safety of hepatic resection.
      LHL15 contributes to the classification by predicting histological liver
      fibrosis.

PMID- 24686197
TI  - Purine nucleoside phosphorylase activity decline is linked to the decay of the
      trimeric form of the enzyme.
AB  - Homotrimeric mammalian purine nucleoside phosphorylase (PNP) plays a key role in
      the nucleoside and nucleotide metabolic salvage pathway. Each monomer in the
      active PNP trimer is composed of a central beta-sheet flanked by several alpha
      helices. We investigated the stability of calf PNP using analytical
      ultracentrifugation, differential scanning calorimetry, circular dichroism, and
      UV absorption spectroscopy. The results demonstrate that the activity decline
      (due to protein aging after isolation from cells) of wild type PNP and its two
      mutants with point mutations in the region of monomer-monomer interface, is
      accompanied by a decrease of the population of the trimeric enzyme and an
      increase of the population of its aggregated forms. The data do not indicate a
      significant population of either folded or unfolded PNP monomers. The enzyme with
      specific activity lower than the maximal shows a decrease of the helical
      structure, which can make it prone to aggregation. The presence of phosphate
      stabilizes the enzyme but leads to a more pronounced aggregation above the
      melting temperature. These results suggest that the biological role of packing of
      the PNP monomers into a trimeric structure is to provide the stability of the
      enzyme since the monomers are not stable in solution. 

PMID- 24686198
TI  - Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and
      review of the literature.
AB  - Sarcoidosis is a rare, systemic disease that is characterized by the formation of
      granulomas in various organs, including the skin. As the etiology remains
      unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old
      female patient with progressive, multi-organ sarcoidosis who had a complete
      clinical improvement of the skin lesions, a moderate reduction in pulmonary
      opacities on chest X-ray, a marked subjective improvement in general status and
      pulmonary efficiency and a marked reduction in serum angiotensin-converting
      enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric
      acid esters. The present case and similar reports in the literature highlight the
      probable efficacy of fumaric acid esters in the treatment of sarcoidosis and
      other non-infectious, granulomatous diseases.

PMID- 24686199
TI  - Obesity. Looking at the epigenetic link between obesity and its consequences--the
      promise of EWAS.

PMID- 24686200
TI  - Diabetes. Cognitive decline and T2DM--a disconnect in the evidence?
AB  - Type 2 diabetes mellitus is associated with an increased risk of cognitive
      decline and dementia. Observational data suggest that hyperglycaemia,
      hypertension and dyslipidaemia might be involved in the causal pathway underlying
      this link, but data from the ACCORD MIND investigators challenge these findings.
      Why are the findings of observational and intervention studies so disconnected?

PMID- 24686201
TI  - Diabetes. Altered gut microbial networks linked to islet cell autoimmunity.

PMID- 24686202
TI  - Bone. Maximizing bone health--magnesium, BMD and fractures.
AB  - The contribution of nutrition to bone health has been heavily debated for many
      years resulting in unclear recommendations for patients regarding prevention of
      bone loss and subsequent fractures. A recent cohort study has examined the
      relationships between magnesium intake, BMD and fractures.

PMID- 24686203
TI  - Neuroendocrine cancer. Closing the GAPP on predicting metastases.
AB  - A promising grading system to predict metastasis in patients with
      phaeochromocytoma and paraganglioma assigns risk according to selected
      histological and other criteria. Such risk stratification might be useful for
      personalized management and screening programmes, as it could limit the costs of
      follow-up and reduce the risk of disseminated disease.

PMID- 24686204
TI  - A new and efficient method for the synthesis of Ulipristal acetate.
AB  - In this study, we describe another new and efficient route for preparing
      Ulipristal acetate. The 1,4-addition compound 5 was greatly improved after the
      starting material ketone 1 was underwent epoxidation, cyanation, hydroxyl group
      protection and Grignard addition. The synthetic procedure is only 6 steps and the
      total yield is about 27.4%, which is much suitable for industrial process. 

PMID- 24686205
TI  - Synthesis of steroidal and nonsteroidal vicinal heterocyclic alcohols, N-(1
      cycloalkenyl)heterocycles and their antibacterial studies.
AB  - A solvent free steroidal and nonsteroidal epoxide ring opening reaction by
      nitrogen containing heterocycles under microwave irradiation is described. Some
      of the epoxide ring opening compounds were converted to their corresponding N-(1
      cycloalkenyl)heterocycles via an acid catalyzed dehydration reaction. The
      antimicrobial activities of the epoxide ring opening compounds and N-(1
      cycloalkenyl)heterocyclic compounds were tested by agar diffusion assay.
      Compounds 6, 9-12, 24 and 27 showed moderate inhibition against the growth of
      pathogenic bacteria Escherichia coli, Pseudomonas syringae, Bacillus subtilis,
      Proteus vulgaris and Staphylococcus aureus. 

PMID- 24686206
TI  - Heterocyclic ring extension of estrone: synthesis and cytotoxicity of fused
      pyran, pyrimidine and thiazole derivatives.
AB  - The one pot reaction of estrone with the aromatic aldehydes 2a-c and either of
      malononitrile or ethyl cyanoacetate afforded the fused pyran derivatives 4a-f. On
      the other hand, carrying the same reaction using thiourea instead of the
      cyanomethylene reagent gave the fused pyrimidine derivatives 6a-c. The latter
      compounds reacted with phenacyl bromide to give the thiazolo[3,2-a]pyrimidine
      derivatives 8a-c. The reaction of the title compound with bromine gave the
      monobromo derivative 13 which in turn reacted with either thiourea or
      cyanothioacetamide to give the thiazole derivatives 14 and 16, respectively. The
      cytotoxicity of the newly synthesized products was evaluated against six human
      cancer and normal cell lines where the results showed that compounds 4c, 4f, 6b,
      8b, 8c, 10, 13, 16, 18c and 19c exhibited optimal cytotoxic effect against the
      cancer cell lines, with IC50's in the nM range. 

PMID- 24686207
TI  - Adrenocortical function in hypotensive patients with end stage renal disease.
AB  - BACKGROUND: Sustained hypotension among patients with end stage renal disease on
      dialysis (ESRDh) varies from 5.0% to 12.0%. Despite their role in the regulation
      of blood pressure (BP) corticoadrenal hormones have been poorly investigated.
      OBJECTIVES: This study aims to detect adrenal insufficiency in ESRDh and follow
      their clinical outcome. METHODS: Fifty ESRDh and 30 healthy volunteers were
      studied. In all cases basal blood and saliva were obtained. Synthetic ACTH
      (25MUg) was injected intramuscularly and at 30min saliva was collected.
      Circulating ACTH, renin, cortisol and aldosterone were measured and steroids were
      also assessed in saliva by immunoassay. RESULTS: Fifteen ESRDh achieved steroid
      responses not different than healthy volunteers; four had primary adrenal
      insufficiency; six had secondary adrenal insufficiency; nine had selective
      hypoaldosteronism and sixteen secondary hyperaldosteronism. The years on dialysis
      did not differ among subgroups. ROC analysis defined the following cut-offs for
      basal cortisol to predict adrenal insufficiency: in serum ?232.0nM (sensitivity
      (S) 100.0% and specificity (E) 90.0%); in saliva ?4.4nM (100.0% S and E). Basal
      aldosterone cut-off values to predict hyperaldosteronism were: in serum >500.0pM
      and saliva >60.0pM (100.0% S and E, for both). For the prediction of
      hypoaldosteronism the basal serum aldosterone was ?260.0pM (100% S; 53% E) and in
      saliva it was ?20.1pM (100% S; 58.5% E). Three patients with primary adrenal
      insufficiency and six with secondary adrenal insufficiency improved general
      clinical condition and normalized BP on steroids. One patient died before
      initiation of steroid therapy. CONCLUSION: Adrenal function should be assessed in
      ESRDh in order to unmask adrenal insufficient states.

PMID- 24686208
TI  - Analysis of sitosteryl oleate esters in phytosterols esters enriched foods by
      HPLC-ESI-MS(2.).
AB  - Phytosteryl esters (PE)-enriched spreads are marketed for eating and cooking
      purposes. Temperature and also light exposure are the major factors leading to
      the formation of PE oxides in food matrix. In this study a high-speed HPLC-MS(2)
      method was developed to analyze the major PE present in PE-enriched spreads:
      sitosteryl oleate (SO) and its oxidation products, by using synthesized compounds
      as standards. This analytical method was used to quantify seven SO oxides formed
      in PE-enriched spreads after heating at different temperatures for varying time
      periods and after prolonged exposure to sunlight. Quantification of remaining
      native SO was also performed after these different treatments. It was found that
      under specific heating conditions the decrease of the SO amount was much more
      important compared to the formation of SO oxides showing that many other products
      are formed. In contrast to heating, sunlight radiation did not result in the
      degradation of SO and very few oxides were formed. 

PMID- 24686209
TI  - Correlation between histologic and radiographic reconstruction of intracochlear
      electrode position in human temporal bones.
AB  - In our laboratory, human temporal bone specimens from patients who in life have
      undergone cochlear implantation are routinely processed with the implant in situ,
      embedded in Araldite, sectioned at 20 um and serially photographed during
      cutting, stained with toluidine blue and mounted on glass slides. From the
      images, two-dimensional and three-dimensional reconstructions can be made and a
      very accurate implant insertion depth can be calculated from the three
      dimensional reconstructions. However, this method precludes subsequent special
      stains and further molecular investigations of the tissue including proteomics
      and immunostaining, which is now possible with celloidin-embedded tissue. In this
      study, we correlated measurement of the implant array insertion depth calculated
      from histologic three-dimensional reconstruction with that measured from three
      dimensional radiologic multiplanar reconstruction. Four human temporal bones with
      cochlear implants underwent postfixation preprocessing CT imaging with a Siemens
      Somatom Sensation Scanner. The CT scans from these four bones were downloaded
      into the Voxar software application, reformatted using the multiplanar
      reconstruction tool, viewed in three dimensions and measurements of intracochlear
      insertion lengths of the implants were obtained. The bones were processed
      routinely for in situ Araldite embedding, serial images were made of the block
      during sectioning, postprocessed using PV-Wave(r) software, aligned with Amira(r)
      software, and used to create histologic three-dimensional reconstructions. From
      these three-dimensional reconstructions, the insertion depth of the electrode
      array was mathematically calculated. The range of insertion depths was 15.9 mm
      (case 1) to 26.6 mm (case 4). The two methods, radiographic multiplanar
      reconstruction and three-dimensional reconstruction, differed by 0.4-0.9%. This
      provides confidence that important localization information about the electrode
      in situ can be gleaned from CT scans, thereby allowing us to extract the implants
      prior to processing for celloidin embedment and allow further techniques such as
      special stains and immunostaining to be accomplished in order to evaluate
      molecular mechanisms involved in cochlear implantation.

PMID- 24686210
TI  - Gated SPECT myocardial perfusion imaging, intraventricular synchronism, and
      cardiac events in heart failure.
AB  - PURPOSE: The purpose of this study was to evaluate the ability of rest gated
      SPECT myocardial perfusion imaging (MPI) and intraventricular synchronism, to
      identify heart failure (HF) patients most likely to experience cardiac events.
      METHODS: We studied 165 patients with left ventricular ejection fraction of less
      than 40%, who were divided in 2 groups according to the diagnosis of coronary
      artery disease (group 1: 136 patients) or not (group 2: 29 patients). All
      underwent a rest gated SPECT MPI. RESULTS: In 160 patients, the MPI was abnormal.
      Mean summed rest score was 17 +/- 6 (group 1) versus 10 +/- 6 (group 2), P <
      0.0001. Mean volumes showed a marked ventricular dilation, slightly higher among
      nonischemic. The mean value of the phase-derived SD was 70 +/- 19 (group 1)
      versus 59 +/- 21 degrees (group 2), P = 0.016. The histogram bandwidth showed no
      significant differences. Forty-four (39%) of 114 patients showed some kind of
      event during the follow-up. The more frequent events were HF progression (13%)
      and acute coronary syndrome (11%). The highest odds ratios for prediction of
      events were 1.91 (phase SD), 1.66 (etiology), and 1.55 (summed rest score),
      although the association was not significant. CONCLUSIONS: A rest gated SPECT is
      a valid approach to identify HF patients most likely to experience cardiac
      events.

PMID- 24686211
TI  - Importance of SPECT/CT images in a case to differentiate a chest wall soft tissue
      infection from pneumonia on 111In-tagged WBC scintigraphy.
AB  - A 52-year-old man presented to the emergency department with a 3-day history of
      fevers and left flank pain radiating to the chest and neck. Total WBC count was
      20,000/uL. Abdominal CT demonstrated small bibasilar pleural effusions. Because
      of persistent leukocytosis, an In WBC scintigram was ordered 5 days after
      admission, which demonstrated thoracic WBC accumulation on the planar images that
      localized to the left posterior chest wall on SPECT/CT. SPECT/CT may
      differentiate intrathoracic versus extrathoracic disease. 

PMID- 24686212
TI  - Lingual tonsillar metastasis from rectal carcinoma: a rare occurrence.
AB  - A 66-year-old man presenting with sacral pain 18 months after radical
      transabdominal resection of rectal mucinous adenocarcinoma underwent F-FDG PET/CT
      cancer surveillance. Detection of multiple nodules in lingual tonsil and left
      neck by imaging initially suggested tonsillar squamous carcinoma (as a second
      primary) with spread to cervical nodes, given the rarity with which rectal
      carcinoma metastasizes to the head and neck. Ultimately, the tonsillar neoplasm
      proved to be adenocarcinoma of colorectal origin based on its shared histologic
      features and compatible immunostaining profile. 

PMID- 24686213
TI  - Brain metastasis in carcinoma breast demonstrated on (68)Ga NOTA-bisphosphonate
      PET/CT.
AB  - Ga NOTA-bisphosphonate is a new bone-seeking PET radiotracer undergoing clinical
      evaluation. We report a case of a carcinoma breast who underwent Ga NOTA
      bisphosphonate PET/CT for detection of skeletal metastasis. In addition to
      skeletal metastasis, a focal area of abnormal radiotracer uptake was noted in the
      brain, which was confirmed as brain metastasis on MRI. 

PMID- 24686214
TI  - Giant urinary bladder stone: incidental finding in (99m)Tc-DTPA renography.
AB  - A 27-year-old woman presented with a history of recurrent urinary tract
      infections in infancy and urinary incontinence secondary to lipomyelomeningocele.
      At the age of 7, she underwent bladder augmentation enterocystoplasty, requiring
      intermittent catheterization without urinary tract infections until present. A Tc
      DTPA renography was performed to evaluate renal function, in which an abnormal
      tracer distribution was seen in urinary bladder, and furthermore, a retrograde
      cystography shows a giant bladder stone. 

PMID- 24686215
TI  - (18)F-FDG PET/CT imaging of malignant hepatic solitary fibrous tumor.
AB  - Solitary fibrous tumor of the liver was rarely documented. F-FDG PET/CT imaging
      of malignant hepatic solitary fibrous tumor in a 49-year-old male patient was
      reported. The multifocal hepatic lesions demonstrated avid FDG uptake. FDG PET/CT
      might be potentially useful in the differentiation of benign and malignant
      solitary fibrous tumor. 

PMID- 24686216
TI  - 18F-FDG-avid brunner gland hyperplasia.
AB  - Brunner gland hyperplasia, a rare duodenal tumor, usually presents with benign
      features. A 68-year-old man with a history of anemia presented with a polypoid
      duodenal mass that was detected by CT and esophagogastroduodenoscopy. This mass
      showed high F-FDG avidity on PET/CT and was histopathologically confirmed as
      Brunner gland hyperplasia. We suggest that Brunner gland hyperplasia should be
      considered in the differential diagnosis of F-FDG-avid duodenal tumors. 

PMID- 24686217
TI  - 18F-FDG PET/CT in tumefactive multiple sclerosis.
AB  - A 35-year-old man underwent contrast-enhanced MRI and F-FDG PET/CT for acute
      peripheral paresthesia, vision loss, muscle weakness, and difficulty walking. T2
      weighted MRI demonstrated multiple bright periventricular supratentorial and
      infratentorial white matter lesions, including 2 with nodularity. Both nodular
      lesions showed moderate focal FDG uptake (SUVmax, 6.9 in both cases).
      Cerebrospinal fluid analysis showed increased levels of immunocytes and
      oligoclonal antibody bands. A diagnosis of acute onset tumefactive multiple
      sclerosis was made. 

PMID- 24686218
TI  - Os trigonum syndrome on bone SPECT/CT.
AB  - A 16-year-old female athlete presented with increased pain in the distal left
      lower extremity. A possible stress fracture or shin splint of the left tibia was
      first considered. A 3-phase bone scintigraphy showed a very small focus of
      increased activity in the posterior left foot. A diagnosis of os trigonum
      syndrome was made after SPECT/CT images pinpointed the activity at the left os
      trigonum. 

PMID- 24686219
TI  - Is the change of integrin alpha(v)beta(3) expression in the infarcted myocardium
      related to the clinical outcome?
AB  - Two adult male patients with myocardial infarction underwent Ga-BNOTA-PRGD2
      (arginine-glycine-aspartic acid [RGD]) PET/CT scans. The initial images that were
      acquired within 1 week after the cardiac event showed RGD retention in the
      infarcted regions in both patients. At follow-up Ga-BNOTA-PRGD2 PET/CT scans, RGD
      uptake was again noticed in the infracted region in the patient who was still had
      symptoms. However, in the patient who had become asymptomatic, RGD uptake in the
      infarcted region was no longer visualized. 

PMID- 24686220
TI  - Rapid analysis and exploration of fluorescence microscopy images.
AB  - Despite rapid advances in high-throughput microscopy, quantitative image-based
      assays still pose significant challenges. While a variety of specialized image
      analysis tools are available, most traditional image-analysis-based workflows
      have steep learning curves (for fine tuning of analysis parameters) and result in
      long turnaround times between imaging and analysis. In particular, cell
      segmentation, the process of identifying individual cells in an image, is a major
      bottleneck in this regard. Here we present an alternate, cell-segmentation-free
      workflow based on PhenoRipper, an open-source software platform designed for the
      rapid analysis and exploration of microscopy images. The pipeline presented here
      is optimized for immunofluorescence microscopy images of cell cultures and
      requires minimal user intervention. Within half an hour, PhenoRipper can analyze
      data from a typical 96-well experiment and generate image profiles. Users can
      then visually explore their data, perform quality control on their experiment,
      ensure response to perturbations and check reproducibility of replicates. This
      facilitates a rapid feedback cycle between analysis and experiment, which is
      crucial during assay optimization. This protocol is useful not just as a first
      pass analysis for quality control, but also may be used as an end-to-end
      solution, especially for screening. The workflow described here scales to large
      data sets such as those generated by high-throughput screens, and has been shown
      to group experimental conditions by phenotype accurately over a wide range of
      biological systems. The PhenoBrowser interface provides an intuitive framework to
      explore the phenotypic space and relate image properties to biological
      annotations. Taken together, the protocol described here will lower the barriers
      to adopting quantitative analysis of image based screens. 

PMID- 24686221
TI  - A novel label-free electrochemical sensor for Hg2+ based on the catalytic
      formation of metal nanoparticle.
AB  - A novel label-free electrochemical sensor has been developed for the highly
      sensitive and selective detection of Hg(2+). Hg(2+) were first captured on the
      modified electrode surface through the specific thymine-Hg(2+)-thymine (T-Hg(2+)
      T) coordination and then through the catalytic HAuCl4/NH2OH reaction for the
      formation of gold nanoparticles (AuNPs) as signal reporter. The formed AuNPs
      could be directly detected by stripping voltammetry. By the introduction of
      graphene to accelerate electron transfer and amplify the electrochemical signal,
      a detection limit as low as 0.06 nM could be obtained for Hg(2+). Compared with
      the traditional metal nanoparticles (NPs)-based method, this sensor avoids the
      labeling of the DNA probe with NP tags, only one unlabeled T-rich DNA sequence
      was needed, which greatly reduced the cost and simplified the sensing procedure.

PMID- 24686222
TI  - Direct electrochemical detection of PB1-F2 protein of influenza A virus in
      infected cells.
AB  - Influenza virus represents a major concern of human health and animal production.
      PB1-F2 is a small proapoptotic protein supposed to contribute to the virulence of
      influenza A virus (IAV). However, the molecular mechanism of action of PB1-F2 is
      still unclear.PB1-F2 expression and behavior during the viral cycle is difficult
      to follow with classical biochemical methods. In this work we have developed an
      electrochemical biosensor based on immuno-detection system for quantification of
      PB1-F2 protein in infected cell. The electrochemical immunosensor was based on
      conducting copolypyrrole integrating ferrocenyl group as redox marker for
      enhancing signal detection. A specific anti-PB1-F2 monoclonal antibody was
      immobilized on the copolypyrrole layer via biotin-streptavidin system. We
      demonstrate that this electrochemical system sensitively detect purified
      recombinant PB1-F2 over a wide range of concentrations from 5 nM to 1.5 uM. The
      high sensor sensitivity allowed the detection of PB1-F2 in lysates of infected
      cells confirming that PB1-F2 is expressed in early stages of viral cycle. The
      immunosensor developed shows enhanced performances for the evaluation of PB1-F2
      protein concentration in biological samples and could be applied for studying of
      PB1-F2 during influenza virus infection.

PMID- 24686223
TI  - Enzyme-induced modulation of the emission of upconverting nanoparticles: towards
      a new sensing scheme for glucose.
AB  - A new approach for the design of a fluorometric biosensor for continuous
      monitoring of glucose levels in biological samples based on near-infrared (NIR)
      excitation is described. The sensor combines the fluorescence of the enzyme
      glucose oxidase (GOx) chemically modified with a fluorescein derivative (FS) and
      the luminescent properties of upconverting luminescent nanoparticles (UCLNPs).
      Both, the chemically modified enzyme (GOx-FS) and the UCLNPs are immobilized in a
      poly(acrylamide) film as a physical support. The excitation of the UCLNPs with
      NIR light is of major advantage, since fluorescence background from the matrix is
      minimized. The upconverted luminescence is used to excite GOx-FS, which undergoes
      a change in the fluorescence intensity during the enzymatic reaction with
      glucose. The sensor comprises sufficient stability and covers the physiological
      range of glucose levels in blood. Furthermore, in a proof of principle
      experiment, the sensor system responds linearly to glucose concentrations in the
      range from 3.3 to 16.6 mM in flow injection analysis mode.

PMID- 24686224
TI  - Chemotherapy drug scheduling for the induction treatment of patients with acute
      myeloid leukemia.
AB  - Leukemia is an immediately life-threatening cancer wherein immature blood cells
      are overproduced, accumulate in the bone marrow (BM) and blood and causes immune
      and blood system failure. Treatment with chemotherapy can be intensive or
      nonintensive and can also be life-threatening since only relatively few patient
      specific and leukemia-specific factors are considered in current protocols. We
      have already presented a mathematical model for one intensive chemotherapy cycle
      with intravenous (i.v.) daunorubicin (DNR), and cytarabine (Ara-C). This model is
      now extended to nonintensive subcutaneous (SC) Ara-C and for a standard intensive
      chemotherapy course (four cycles), consistent with clinical practice. Model
      parameters mainly consist of physiological patient data, indicators of tumor
      burden and characteristics of cell cycle kinetics. A sensitivity analysis problem
      is solved and cell cycle parameters are identified to control treatment outcome.
      Simulation results using published cell cycle data from two acute myeloid
      leukemia patients are presented for a course of standard treatment using
      intensive and nonintensive protocols. The aim of remission-induction therapy is
      to debulk the tumor and achieve normal BM function; by treatment completion, the
      total leukemic population should be reduced to at most 10(9) cells, at which
      point BM hypoplasia is achieved. The normal cell number should be higher than
      that of the leukemic, and a 3-log reduction is the maximum permissible level of
      population reduction. This optimization problem is formulated and solved for the
      two patient case studies. The results clearly present the benefits from the use
      of optimization as an advisory tool for treatment design.

PMID- 24686225
TI  - Position-dependent characterization of passive wrist stiffness.
AB  - Because the dynamics of wrist rotations are dominated by stiffness, understanding
      wrist rotations requires a thorough characterization of wrist stiffness in
      multiple degrees of freedom. The only prior measurement of multivariable wrist
      stiffness was confined to approximately one-seventh of the wrist range of motion
      (ROM). Here, we present a precise nonlinear characterization of passive wrist
      joint stiffness over a range three times greater, which covers approximately 70%
      of the functional ROM of the wrist. We measured the torque-displacement vector
      field in 24 directions and fit the data using thin-plate spline smoothing
      optimized with generalized cross validation. To assess anisotropy and
      nonlinearity, we subsequently derived several different approximations of the
      stiffness due to this multivariable vector field. The directional variation of
      stiffness was more pronounced than reported previously. A linear approximation
      (obtained by multiple linear regression over the entire field) was significantly
      more anisotropic (eigenvalue ratio of 2.69 +/- 0.52 versus 1.58 +/- 0.39; )
      though less misaligned with the anatomical wrist axes (12.1 +/- 4.6 degrees 
      versus 21.2 +/- 9.2 degrees ; ). We also found that stiffness over this range
      exhibited considerable nonlinearity-the error associated with a linear
      approximation was 20-30%. The nonlinear characterization over this greater range
      confirmed significantly greater stiffness in radial deviation compared to ulnar
      deviation. This study provides a characterization of passive wrist stiffness
      better suited to investigations of natural wrist rotations, which cover much of
      the wrist's ROM. It also provides a baseline for the study of neurological and/or
      orthopedic disorders that result in abnormal wrist stiffness. 

PMID- 24686226
TI  - A robust algorithm for thickness computation at low resolution and its
      application to in vivo trabecular bone CT imaging.
AB  - Adult bone diseases, especially osteoporosis, lead to increased risk of fracture
      which in turn is associated with substantial morbidity, mortality, and financial
      costs. Clinically, osteoporosis is defined by low bone mineral density; however,
      increasing evidence suggests that the microarchitectural quality of trabecular
      bone (TB) is an important determinant of bone strength and fracture risk.
      Accurate measures of TB thickness and marrow spacing is of significant interest
      for early diagnosis of osteoporosis or treatment effects. Here, we present a new
      robust algorithm for computing TB thickness and marrow spacing at a low
      resolution achievable in vivo. The method uses a star-line tracing technique that
      effectively deals with partial voluming effects of in vivo imaging with voxel
      size comparable to TB thickness. Also, the method avoids the problem of
      digitization associated with conventional algorithms based on sampling distance
      transform along skeletons. Accuracy of the method was examined using computer
      generated phantom images, while the robustness of the method was evaluated on
      human ankle specimens in terms of stability across a wide range of voxel sizes,
      repeat scan reproducibility under in vivo conditions, and correlation between
      thickness values computed at ex vivo and in vivo imaging resolutions. Also, the
      sensitivity of the method was examined by evaluating its ability to predict the
      bone strength of cadaveric specimens. Finally, the method was evaluated in a
      human study involving 40 healthy young-adult volunteers (age: 19-21 years; 20
      males and 20 females) and ten athletes (age: 19-21 years; six males and four
      females). Across a wide range of voxel sizes, the new method is significantly
      more accurate and robust as compared to conventional methods. Both TB thickness
      and marrow spacing measures computed using the new method demonstrated strong
      associations (R2 ? [0.83, 0.87]) with bone strength. Also, the TB thickness and
      marrow spacing measures allowed discrimination between male and female volunteers
      (p ? [0.01, 0.04]) as well as between athletes and nonathletes (p ? [0.005,
      0.03]).

PMID- 24686228
TI  - Speech enhancement for listeners with hearing loss based on a model for vowel
      coding in the auditory midbrain.
AB  - A novel signal-processing strategy is proposed to enhance speech for listeners
      with hearing loss. The strategy focuses on improving vowel perception based on a
      recent hypothesis for vowel coding in the auditory system. Traditionally, studies
      of neural vowel encoding have focused on the representation of formants (peaks in
      vowel spectra) in the discharge patterns of the population of auditory-nerve (AN)
      fibers. A recent hypothesis focuses instead on vowel encoding in the auditory
      midbrain, and suggests a robust representation of formants. AN fiber discharge
      rates are characterized by pitch-related fluctuations having frequency-dependent
      modulation depths. Fibers tuned to frequencies near formants exhibit weaker pitch
      related fluctuations than those tuned to frequencies between formants. Many
      auditory midbrain neurons show tuning to amplitude modulation frequency in
      addition to audio frequency. According to the auditory midbrain vowel encoding
      hypothesis, the response map of a population of midbrain neurons tuned to
      modulations near voice pitch exhibits minima near formant frequencies, due to the
      lack of strong pitch-related fluctuations at their inputs. This representation is
      robust over the range of noise conditions in which speech intelligibility is also
      robust for normal-hearing listeners. Based on this hypothesis, a vowel
      enhancement strategy has been proposed that aims to restore vowel encoding at the
      level of the auditory midbrain. The signal processing consists of pitch tracking,
      formant tracking, and formant enhancement. The novel formant-tracking method
      proposed here estimates the first two formant frequencies by modeling
      characteristics of the auditory periphery, such as saturated discharge rates of
      AN fibers and modulation tuning properties of auditory midbrain neurons. The
      formant enhancement stage aims to restore the representation of formants at the
      level of the midbrain by increasing the dominance of a single harmonic near each
      formant and saturating that frequency channel. A MATLAB implementation of the
      system with low computational complexity was developed. Objective tests of the
      formant-tracking subsystem on vowels suggest that the method generalizes well
      over a wide range of speakers and vowels. 

PMID- 24686227
TI  - Lasting modulation effects of rTMS on neural activity and connectivity as
      revealed by resting-state EEG.
AB  - The long-lasting neuromodulatory effects of repetitive transcranial magnetic
      stimulation (rTMS) are of great interest for therapeutic applications in various
      neurological and psychiatric disorders, due to which functional connectivity
      among brain regions is profoundly disturbed. Classic TMS studies selectively
      alter neural activity in specific brain regions and observe neural activity
      changes on nonperturbed areas to infer underlying connectivity and its changes.
      Less has been indicated in direct measures of functional connectivity and/or
      neural network and on how connectivity/network alterations occur. Here, we
      developed a novel analysis framework to directly investigate both neural activity
      and connectivity changes induced by rTMS from resting-state EEG (rsEEG) acquired
      in a group of subjects with a chronic disorder of imbalance, known as the mal de
      debarquement syndrome (MdDS). Resting-state activity in multiple functional brain
      areas was identified through a data-driven blind source separation analysis on
      rsEEG data, and the connectivity among them was characterized using a phase
      synchronization measure. Our study revealed that there were significant long
      lasting changes in resting-state neural activity, in theta, low alpha, and high
      alpha bands and neural networks in theta, low alpha, high alpha and beta bands,
      over broad cortical areas 4 to 5 h after the last application of rTMS in a
      consecutive five-day protocol. Our results of rsEEG connectivity further
      indicated that the changes, mainly in the alpha band, over the parietal and
      occipital cortices from pre- to post-TMS sessions were significantly correlated,
      in both magnitude and direction, to symptom changes in this group of subjects
      with MdDS. This connectivity measure not only suggested that rTMS can generate
      positive treatment effects in MdDS patients, but also revealed new potential
      targets for future therapeutic trials to improve treatment effects. It is
      promising that the new connectivity measure from rsEEG can be used to understand
      the variability in treatment response to rTMS in brain disorders with impaired
      functional connectivity and, eventually, to determine individually tailored
      stimulation parameters and treatment procedures in rTMS. 

PMID- 24686230
TI  - Murine heart volume: numerical comparison and calibration of conductance catheter
      models.
AB  - A full set of finite-element method (FEM) studies of the catheter within a
      cylindrical cuvette and within an elliptical cuvette are presented along with
      novel insight on the fundamental electromagnetic properties of the catheter. An
      in vitro experiment with modified small mouse pressure-volume catheters was
      conducted and the results are presented as a validation of the FEM models. In
      addition, sensitivity analysis on the electrode size and position is conducted
      and the results allow for a novel calibration factor based on catheter geometry
      to be presented. This calibration factor is used in conjunction with Wei's
      conductance volume equations to reduce the average measured error in cuvette
      volume measurements from 26.5% to 5%.

PMID- 24686231
TI  - A closed-loop brain-computer interface triggering an active ankle-foot orthosis
      for inducing cortical neural plasticity.
AB  - In this paper, we present a brain-computer interface (BCI) driven motorized ankle
      foot orthosis (BCI-MAFO), intended for stroke rehabilitation, and we demonstrate
      its efficacy in inducing cortical neuroplasticity in healthy subjects with a
      short intervention procedure (~15 min). This system detects imaginary
      dorsiflexion movements within a short latency from scalp EEG through the analysis
      of movement-related cortical potentials (MRCPs). A manifold-based method, called
      locality preserving projection, detected the motor imagery online with a true
      positive rate of 73.0 +/- 10.3%. Each detection triggered the MAFO to elicit a
      passive dorsiflexion. In nine healthy subjects, the size of the motor-evoked
      potential (MEP) elicited by transcranial magnetic stimulation increased
      significantly immediately following and 30 min after the cessation of this BCI
      MAFO intervention for ~15 min ( p = 0.009 and , respectively), indicating neural
      plasticity. In four subjects, the size of the short latency stretch reflex
      component did not change following the intervention, suggesting that the site of
      the induced plasticity was cortical. All but one subject also performed two
      control conditions where they either imagined only or where the MAFO was randomly
      triggered. Both of these control conditions resulted in no significant changes in
      MEP size (p = 0.38 and p = 0.15). The proposed system provides a fast and
      effective approach for inducing cortical plasticity through BCI and has potential
      in motor function rehabilitation following stroke.

PMID- 24686232
TI  - Fast three-material modeling with triple arch projection for electronic cleansing
      in CTC.
AB  - In this paper, we propose a fast three-material modeling for electronic cleansing
      (EC) in computed tomographic colonography. Using a triple arch projection, our
      three-material modeling provides a very quick estimate of the three-material
      fractions to remove ridge-shaped artifacts at the T-junctions where air, soft
      tissue (ST), and tagged residues (TRs) meet simultaneously. In our approach,
      colonic components including air, TR, the layer between air and TR, the layer
      between ST and TR (L(ST/TR)), and the T-junction are first segmented.
      Subsequently, the material fraction of ST for each voxel in L(ST/TR) and the T
      junction is determined. Two-material fractions of the voxels in L(ST/TR) are
      derived based on a two-material transition model. On the other hand, three
      material fractions of the voxels in the T-junction are estimated based on our
      fast three-material modeling with triple arch projection. Finally, the CT density
      value of each voxel is updated based on our fold-preserving reconstruction model.
      Experimental results using ten clinical datasets demonstrate that the proposed
      three-material modeling successfully removed the T-junction artifacts and clearly
      reconstructed the whole colon surface while preserving the submerged folds well.
      Furthermore, compared with the previous three-material transition model, the
      proposed three-material modeling resulted in about a five-fold increase in speed
      with the better preservation of submerged folds and the similar level of
      cleansing quality in T-junction regions.

PMID- 24686229
TI  - Magnetic resonance imaging at ultrahigh fields.
AB  - Since the introduction of 4 T human systems in three academic laboratories circa
      1990, rapid progress in imaging and spectroscopy studies in humans at 4 T and
      animal model systems at 9.4 T have led to the introduction of 7 T and higher
      magnetic fields for human investigation at about the turn of the century. Work
      conducted on these platforms has demonstrated the existence of significant
      advantages in SNR and biological information content at these ultrahigh fields,
      as well as the presence of numerous challenges. Primary difference from lower
      fields is the deviation from the near field regime; at the frequencies
      corresponding to hydrogen resonance conditions at ultrahigh fields, the RF is
      characterized by attenuated traveling waves in the human body, which leads to
      image nonuniformities for a given sample-coil configuration because of
      interferences. These nonuniformities were considered detrimental to the progress
      of imaging at high field strengths. However, they are advantageous for parallel
      imaging for signal reception and parallel transmission, two critical technologies
      that account, to a large extend, for the success of ultrahigh fields. With these
      technologies, and improvements in instrumentation and imaging methods, ultrahigh
      fields have provided unprecedented gains in imaging of brain function and
      anatomy, and started to make inroads into investigation of the human torso and
      extremities. As extensive as they are, these gains still constitute a prelude to
      what is to come given the increasingly larger effort committed to ultrahigh field
      research and development of ever better instrumentation and techniques. 

PMID- 24686233
TI  - Development and validation of an HPLC method for the simultaneous quantification
      of indole-3-carbinol acetate, indole-3-carbinol, and 3,3'-diindolylmethane in
      mouse plasma, liver, and kidney tissues.
AB  - A novel Indole-3-carbinol derivative (I3C) prodrug, indole-3-carbinol acetate
      (I3CA), was synthesized and a rapid high-performance liquid chromatography (HPLC)
      method for the quantification of I3CA, I3C, and the major metabolite of I3C,
      diindolylmethane (DIM), in mouse plasma, liver and kidney tissues was developed
      and validated. 4-Methoxy-1-methylindole was used as the internal standard.
      Chromatographic separation was achieved on a Symmetry((r)) C18 column
      (75mm*4.6mm, 3.5MUm) and the detection was made at 280nm. A gradient elution was
      programmed with the mobile phases of water (A) and acetonitrile (B) and a flow
      rate of 1ml/min. The total run time was 15min. The calibration curves were linear
      over the range of 0.06-1.6MUg/ml for both I3C and DIM with a correlation
      coefficient (r(2)) higher than 0.997 and the lower limit of quantitation (LLOQ)
      of 0.06MUg/ml. The calibration curve of I3CA was linear over the range of 0.15
      4.0MUg/ml, with a r(2)>0.995 and LLOQ of 0.15MUg/ml. I3CA, I3C, and DIM intra-day
      accuracy values of plasma, liver and kidney samples ranged from 90.0 to 101.3%,
      while the inter-day ones were between 93.3 and 101.9%. Precision evaluated by the
      relative standard deviation was ranged from 2.0 to 14.8% for intra-day and 1.9 to
      14.4% for inter-day variability. I3CA, I3C, and DIM were stable in mouse plasma,
      liver and kidney samples containing an esterase inhibitor dichlorvos. This method
      was successfully applied to a pharmacokinetic study in mice following oral and
      intravenous administration of I3C and I3CA. 

PMID- 24686235
TI  - Mobilization of Cd from human serum albumin by small molecular weight thiols.
AB  - Although the toxic metal Cd is an established human nephrotoxin, little is known
      about the role that interactions with plasma constitutents play in determining
      its mammalian target organs. To gain insight, a Cd-human serum albumin (HSA)
      complex was analyzed on a system consisting of size exclusion chromatography
      (SEC) coupled on-line to a flame atomic absorption spectrometer (FAAS). Using
      phosphate buffered saline (pH 7.4) as the mobile phase, we investigated the
      effect of 1-10mM oxidized glutathione (GSSG), l-cysteine (Cys), l-glutathione
      (GSH), or N-acetyl-l-cysteine (NAC) on the elution of Cd. As expected, GSSG did
      not mobilize Cd from the Cd-HSA complex up to a concentration of 4mM. With 1.0mM
      NAC, ~30% of the injected Cd-HSA complex eluted as such, while the mobilized Cd
      was lost on the column. With 1.0mM of Cys or GSH, no parent Cd-HSA complex was
      detected and 88% and 82% of the protein bound Cd eluted close to the elution
      volume, likely in form of Cd(Cys)2 and a Cd-GSH 1:1 complex. Interestingly, with
      GSH and NAC concentrations >4.0mM, a Cd double peak was detected, which was
      rationalized in terms of the elution of a polynuclear Cd complex baseline
      separated from a mononuclear Cd complex. In contrast, mobile phases which
      contained Cys concentrations >=2mM resulted in the detection of only a single Cd
      peak, probably Cd(Cys)4. Our results establish SEC-FAAS as a viable tool to probe
      the mobilization of Cd from binding sites on plasma proteins at near
      physiological conditions. The detected complexes between Cd and Cys or GSH may be
      involved in the translocation of Cd to mammalian target organs. 

PMID- 24686234
TI  - A novel method for simultaneous measurement of concentration and enrichment of NO
      synthesis-specific amino acids in human plasma using stable isotopes and LC/MS
      ion trap analysis.
AB  - Stable isotope studies offer the opportunity to study the in-depth metabolic
      pathway of glutamine, citrulline, and arginine amino acids involved in NO
      synthesis. The use of multiple stable isotopes can be used to elucidate the exact
      transformation of glutamine to citrulline and arginine de novo synthesis. This
      novel method provides a purification step using cation exchange resin in
      combination with a rapid and easy derivatization procedure for a precise and
      robust measurement of the concentration and isotopic enrichments of NO synthesis
      specific amino acids using a liquid chromatography mass spectrometry (LC/MS) ion
      trap system with high sensitivity and selectivity. The ethyl chloroformate
      derivatization procedure is beneficial in terms of robustness, velocity,
      simplicity, and derivative stability. In addition, the ethyl chloroformate
      derivatization can be performed at room temperature in an aqueous environment
      without incubation and the isolation of the derivatives from the reaction mixture
      also serves as a purification step. The concentration and enrichment of NO
      synthesis-specific amino acids as well as phenylalanine and tyrosine to determine
      protein turnover, were measured with good inter-day precision for the
      concentration (<7.4%) and enrichment (<12.7%) in plasma samples at low and high
      levels. The low limit of quantification was 0.2MUmol/L for most of the amino
      acids and the purification method showed to have good recoveries between 78% and
      98%. No ion-suppression was observed by post-column infusion experiments. In
      order to develop new nutritional strategies, this novel method can be used to
      support the elucidation of the effect of administration of specific supplements
      on the glutamine-citrulline-arginine pathway by using stable isotope studies. 

PMID- 24686236
TI  - Comparison of different sorbent materials for solid-phase extraction of selected
      drugs in human urine analyzed by UHPLC-UV.
AB  - A procedure based on solid-phase extraction (SPE) followed by ultra-high
      performance liquid chromatography (UHPLC) with UV detection has been developed
      for the analysis of multiple drugs in human urine. The compounds evaluated were
      aliskiren, prasugrel, rivaroxaban, prednisolone, propranolol, ketoprofen,
      nifedipine, naproxen, terbinafine, ibuprofen, diclofenac, sildenafil and
      acenocoumarol. Seventeen different solid phase extraction (SPE) cartridges were
      tested to evaluate their applicability for the isolation of drugs from human
      urine. Comparison were recovery of different drugs and reproducibility. The
      samples were analyzed by UHPLC using a Poroshell 120 EC-C18 column and
      acetonitrile -0.05% TFA in water as the mobile phase under gradient elution
      conditions. SPE combined with UHPLC-UV allowed the determination of drugs over a
      linear range of 0.01-30.0MUg/mL, with limits of detection at 0.003-0.217MUg/mL
      and precision of 0.8-7.1%. Phenyl (C6H5) sorbent was found to provide the most
      effective clean-up, removing the greatest amount of interfering substance and
      simultaneously ensuring analyte recoveries higher than 85.5% with relative
      standard deviations (RSD) <10%. The method was applied with good accuracy and
      precision in the determination of drugs in human urine obtained from patients
      treated with selected drugs. 

PMID- 24686238
TI  - Analysis and determination of oestrogen-active compounds in fructus amomi by the
      combination of high-speed counter-current chromatography and high performance
      liquid chromatography.
AB  - Amomum longiligulare or Amomum villosum showed oestrogenic activity. In the
      present study, oestrogen-active components in fructus amomi, the seeds of A.
      longiligulare were separated by high-speed countercurrent chromatography (HSCCC)
      using stepwise elution of eight mobile phases with gradient polarity and advanced
      separation by high performance liquid chromatography (HPLC). The results yielded
      17 compounds with the amount of 8-138mg and a purity of 94.3-99.8% from a 3g
      ethanolic extract of fructus amomi. The chemical structures of the compounds were
      identified by ESI-MS and NMR spectra, in which eight diarylheptanoids were
      demonstrated as the main oestrogen-active compounds in the fructus amomi.
      Determination of the diarylheptanoids in fructus amomi from various origins
      showed that fructus amomi contains more than 0.5% total diarylheptanoids. The
      results showed that fructus amomi is a diarylheptanoids-rich food resource
      possessing oestrogen-activity. The combination method of HSCCC and HPLC can be
      applied for the analysis of bioactive compounds by detecting the corresponding
      bioactivity in the HSCCC fractions and separating the target compounds with HPLC.

PMID- 24686237
TI  - Liquid chromatography-tandem mass spectrometry method for simultaneous
      quantification of bisoprolol, ramiprilat, propranolol and midazolam in rat dried
      blood spots.
AB  - Dried blood spot (DBS) sampling represents a suitable method for pharmacokinetic
      studies in rats, particularly if serial sampling is needed. To study the
      pharmacokinetics of drugs in a rat heart failure (HF) model, we developed and
      validated a method for the simultaneous determination of bisoprolol, ramiprilat,
      propranolol and midazolam in DBS samples. Bisoprolol and ramipril are widely used
      in the treatment of HF, and midazolam and propranolol are markers of hepatic
      metabolism, which can be altered in HF. A 20MUL sample of rat blood was pipetted
      onto Whatman 903 Protein Saver Card and allowed to dry. The whole spot was
      excised and 300MUL of solvent (methanol with 10% ultrapure water and 0.1% formic
      acid) was added. After mixing and incubating the sample in an ultrasonic bath, a
      mixture of isotopically labeled internal standards was added. After
      centrifugation, the extracts were cleaned on an OstroTM plate and analyzed using
      liquid chromatography-tandem mass spectroscopy. The method was successfully
      validated. No significant interference was observed in the retention times of
      analytes or internal standards. The intraday and interday accuracy and precision
      were within a +/-15% interval. The method was linear in the range 5-250MUg/L and
      the lower limit of quantification was 5MUg/L for all four analytes. The absolute
      matrix effect ranged from 98.7% for midazolam to 121% for ramiprilat. The
      recovery was lowest for ramiprilat and highest for propranolol. Samples were
      stable at all tested temperatures. The method has been used successfully in a
      real-time pharmacokinetic study in rats. 

PMID- 24686239
TI  - Manipulability impairs association-memory: revisiting effects of incidental motor
      processing on verbal paired-associates.
AB  - Imageability is known to enhance association-memory for verbal paired-associates.
      High-imageability words can be further subdivided by manipulability, the ease by
      which the named object can be functionally interacted with. Prior studies suggest
      that motor processing enhances item-memory, but impairs association-memory.
      However, these studies used action verbs and concrete nouns as the high- and low
      manipulability words, respectively, confounding manipulability with word class.
      Recent findings demonstrated that nouns can serve as both high- and low
      manipulability words (e.g., CAMERA and TABLE, respectively), allowing us to avoid
      this confound. Here participants studied pairs of words that consisted of all
      possible pairings of high- and low-manipulability words and were tested with
      immediate cued recall. Recall was worse for pairs that contained high
      manipulability words. In free recall, participants recalled more high- than low
      manipulability words. Our results provide further evidence that manipulability
      influences memory, likely occurring through automatic motor imagery. 

PMID- 24686240
TI  - Properties of the size-weight illusion as shown by lines of subjective equality.
AB  - We studied the size-weight illusion through comparative judgments. The experiment
      had two direct aims: to verify whether the relative contribution of size to
      apparent heaviness can differ for different stimulus sets, and to verify whether
      that contribution can differ for different methods of comparing two objects
      (consecutive vs. simultaneous weighing). Thirty university students participated.
      Results show that the relative contribution of size depends on stimulus set, but
      is independent of the method used for comparing objects. The first finding
      implies that a linear model cannot describe the integration of size and weight
      information in the illusion; the second finding is evidence for the low-level
      character of the integration process. 

PMID- 24686241
TI  - Quantum rotor in nanostructured superconductors.
AB  - Despite its apparent simplicity, the idealized model of a particle constrained to
      move on a circle has intriguing dynamic properties and immediate experimental
      relevance. While a rotor is rather easy to set up classically, the quantum regime
      is harder to realize and investigate. Here we demonstrate that the quantum
      dynamics of quasiparticles in certain classes of nanostructured superconductors
      can be mapped onto a quantum rotor. Furthermore, we provide a straightforward
      experimental procedure to convert this nanoscale superconducting rotor into a
      regular or inverted quantum pendulum with tunable gravitational field, inertia,
      and drive. We detail how these novel states can be detected via scanning
      tunneling spectroscopy. The proposed experiments will provide insights into
      quantum dynamics and quantum chaos. 

PMID- 24686242
TI  - Suppression of murine colitis and its associated cancer by carcinoembryonic
      antigen-specific regulatory T cells.
AB  - The adoptive transfer of regulatory T cells (Tregs) offers a promising strategy
      to combat pathologies that are characterized by aberrant immune activation,
      including graft rejection and autoinflammatory diseases. Expression of a chimeric
      antigen receptor (CAR) gene in Tregs redirects them to the site of autoimmune
      activity, thereby increasing their suppressive efficiency while avoiding systemic
      immunosuppression. Since carcinoembryonic antigen (CEA) has been shown to be
      overexpressed in both human colitis and colorectal cancer, we treated CEA
      transgenic mice that were induced to develop colitis with CEA-specific CAR Tregs.
      Two disease models were employed: T-cell-transfer colitis as well as the
      azoxymethane-dextran sodium sulfate model for colitis-associated colorectal
      cancer. Systemically administered CEA-specific (but not control) CAR Tregs
      accumulated in the colons of diseased mice. In both model systems, CEA-specific
      CAR Tregs suppressed the severity of colitis compared to control Tregs. Moreover,
      in the azoxymethane-dextran sodium sulfate model, CEA-specific CAR Tregs
      significantly decreased the subsequent colorectal tumor burden. Our data
      demonstrate that CEA-specific CAR Tregs exhibit a promising potential in
      ameliorating ulcerative colitis and in hindering colorectal cancer development.
      Collectively, this study provides a proof of concept for the therapeutic
      potential of CAR Tregs in colitis patients as well as in other autoimmune
      inflammatory disorders. 

PMID- 24686243
TI  - Adrenal incidentalomas: management in British district general hospitals.
AB  - INTRODUCTION: Adrenal incidentalomas have become a common clinical dilemma with
      the increasing use and resolution of cross sectional imaging modalities.
      OBJECTIVES: This retrospective observational study examined the management of
      adrenal incidentalomas in district general hospitals in Northumbria and adherence
      to current guidelines. MATERIALS AND METHODS: We searched 4028 abdominal CT scans
      performed in Northumbria between 1 January and 31 December 2010. All patients
      with an incidental adrenal lesion were identified and their clinical records
      reviewed. RESULTS: 75 patients with adrenal incidentalomas were identified. Of
      these, only 13 (17%) were referred for specialist review with a further two
      patients undergoing additional evaluation by the primary medical team; 80%
      received no biochemical investigation or follow-up. Comorbidity may have affected
      the decision in a proportion, but 36 of 62 patients (58%) had no comorbidities
      precluding additional evaluation. In contrast, all patients reviewed by an
      endocrine specialist were appropriately investigated and managed, the majority
      conservatively, with three requiring adrenalectomy for phaeochromocytoma or
      cortisol secreting adenomas. In the patients with an incidentaloma, comorbidities
      which may be attributable to autonomous adrenal cortisol or aldosterone release
      were higher than regional averages, suggesting possible undiagnosed functional
      tumours. CONCLUSIONS: The management of adrenal incidentalomas in British
      district general hospitals in Northumbria shows poor adherence to guidelines.
      Adherence was significantly better in those patients managed by an endocrine
      specialist. We suggest a pathway for the management and referral process.

PMID- 24686244
TI  - FMT-PCCT: hybrid fluorescence molecular tomography-x-ray phase-contrast CT
      imaging of mouse models.
AB  - The implementation of hybrid fluorescence molecular tomography (FMT) and X-ray
      computed tomography (CT) has been shown to be a necessary development, not only
      for combining anatomical with functional and molecular contrast, but also for
      generating optical images of high accuracy. FMT affords highly sensitive 3-D
      imaging of fluorescence bio-distribution, but in stand-alone form it offers
      images of low resolution. It was shown that FMT accuracy significantly improves
      by considering anatomical priors from CT. Conversely, CT generally suffers from
      low soft tissue contrast. Therefore utilization of CT data as prior information
      in FMT inversion is challenging when different internal organs are not clearly
      differentiated. Instead, we combined herein FMT with emerging X-ray phase
      contrast CT (PCCT). PCCT relies on phase shift differences in tissue to achieve
      soft tissue contrast superior to conventional CT. We demonstrate for the first
      time FMT-PCCT imaging of different animal models, where FMT and PCCT scans were
      performed in vivo and ex vivo, respectively. The results show that FMT-PCCT
      expands the potential of FMT in imaging lesions with otherwise low or no CT
      contrast, while retaining the cost benefits of CT and simplicity of hybrid device
      realizations. The results point to the most accurate FMT performance to date. 

PMID- 24686245
TI  - Metric optimization for surface analysis in the Laplace-Beltrami embedding space.
AB  - In this paper, we present a novel approach for the intrinsic mapping of
      anatomical surfaces and its application in brain mapping research. Using the
      Laplace-Beltrami eigen-system, we represent each surface with an isometry
      invariant embedding in a high dimensional space. The key idea in our system is
      that we realize surface deformation in the embedding space via the iterative
      optimization of a conformal metric without explicitly perturbing the surface or
      its embedding. By minimizing a distance measure in the embedding space with
      metric optimization, our method generates a conformal map directly between
      surfaces with highly uniform metric distortion and the ability of aligning
      salient geometric features. Besides pairwise surface maps, we also extend the
      metric optimization approach for group-wise atlas construction and multi-atlas
      cortical label fusion. In experimental results, we demonstrate the robustness and
      generality of our method by applying it to map both cortical and hippocampal
      surfaces in population studies. For cortical labeling, our method achieves
      excellent performance in a cross-validation experiment with 40 manually labeled
      surfaces, and successfully models localized brain development in a pediatric
      study of 80 subjects. For hippocampal mapping, our method produces much more
      significant results than two popular tools on a multiple sclerosis study of 109
      subjects. 

PMID- 24686246
TI  - Invasive aspergillosis in children with acute leukemia at a resource-limited
      oncology center.
AB  - BACKGROUND: Invasive aspergillosis (IA) is one of the most feared complications
      in patients with hematologic malignancies because it is associated with high
      morbidity and mortality, and significantly compromises antileukemia therapy.
      OBJECTIVES: Analyze all patients with acute leukemia and IA of less than 18 years
      of age, diagnosed between January 1996 and December 2011. MATERIALS AND METHODS:
      Cases were identified from the pediatric database for demographic details,
      disease characteristics, and IA-related data. RESULTS: Among 356 patients with
      acute leukemia, 34 were identified to have proven/probable IA (5/29) with a
      relative incidence of 9% (28/310) and 13% (6/46) among acute lymphoblastic
      leukemia (ALL) and acute myeloid leukemia, respectively. Incidence of IA was
      significantly higher after 2004 especially among ALL patients; older patients
      with hyperglycemia and high-risk disease were more predisposed. None of the risk
      factors or type of antifungal treatment predicted mortality. The 120-day
      aspergillus-attributable mortality rate was 14.7%. IA led to a median of 17 days
      (2 to 44 d) of additional hospital stay and contributed to delay or reduction in
      planned chemotherapy in 30/34 patients. CONCLUSIONS: An increasing trend in
      incidence of IA was observed during the latter half of study period. Early
      empiric therapy led to modest aspergillus-free survival. Clinical and financial
      implications of IA mandate review of institutional antifungal prophylaxis policy
      especially in selected ALL patients during induction.

PMID- 24686247
TI  - Optimized protocols for Mycobacterium leprae strain management: frozen stock
      preservation and maintenance in athymic nude mice.
AB  - Leprosy, caused by Mycobacterium leprae, is an important infectious disease that
      is still endemic in many countries around the world, including Brazil. There are
      currently no known methods for growing M. leprae in vitro, presenting a major
      obstacle in the study of this pathogen in the laboratory. Therefore, the
      maintenance and growth of M. leprae strains are preferably performed in athymic
      nude mice (NU-Foxn1(nu)). The laboratory conditions for using mice are readily
      available, easy to perform, and allow standardization and development of
      protocols for achieving reproducible results. In the present report, we describe
      a simple protocol for purification of bacilli from nude mouse footpads using
      trypsin, which yields a suspension with minimum cell debris and with high
      bacterial viability index, as determined by fluorescent microscopy. A
      modification to the standard method for bacillary counting by Ziehl-Neelsen
      staining and light microscopy is also demonstrated. Additionally, we describe a
      protocol for freezing and thawing bacillary stocks as an alternative protocol for
      maintenance and storage of M. leprae strains. 

PMID- 24686248
TI  - Diagnostic value of 99mTc-bombesin scintigraphy for differentiation of malignant
      from benign breast lesions.
AB  - OBJECTIVE: In this study, we evaluated the diagnostic accuracy of (99m)Tc
      bombesin scintigraphy for differentiation of benign from malignant palpable
      breast lesions. (99m)Tc-Bombesin is a tracer with high affinity for gastrin
      releasing peptide receptor, which is overexpressed on a variety of human tumors
      including breast carcinoma. MATERIALS AND METHODS: We examined 33 consecutive
      women who were referred to our center with suspicious palpable breast lesions but
      had no definitive diagnosis in other imaging procedures. A volume of 370-444 MBq
      of (99m)Tc-bombesin was injected and dynamic 1-min images were taken for 20 min
      immediately after injection in anterior view. Thereafter, two static images in
      anterior and prone-lateral views were taken for 5 min. Finally, single-photon
      emission computed tomography images were taken for each patient. Definitive
      diagnosis was based on biopsy and histopathological evaluation. RESULTS: The scan
      findings were positive in 19 patients and negative in 11 on visual assessment of
      the planar and single-photon emission computed tomography images. Pathologic
      examination confirmed breast carcinoma in 12 patients with positive scans and
      benign pathology for 18 patients. The overall sensitivity, specificity, negative
      and positive predictive values, and accuracy of this radiotracer for diagnosis of
      breast cancer were 100, 66.1, 100, 63, and 76%, respectively. Semiquantitative
      analysis improved the specificity of the visual assessment from 66 to 84%.
      CONCLUSION: Our study showed that (99m)Tc-bombesin scintigraphy has a high
      sensitivity and negative predictive value for detecting malignant breast lesions,
      but the specificity and positive predictive value of this radiotracer for
      differentiation of malignant breast abnormalities from benign ones are relatively
      low.

PMID- 24686249
TI  - Are PREDIST criteria better than PERCIST criteria as a PET predictor of
      preoperative treatment response in rectal cancer?
AB  - Fluorine-18-fluorodeoxyglucose PET/CT is an accurate tool for predicting the
      response to preoperative chemoradiotherapy in locally advanced rectal cancer
      patients. The need for standardization has contributed to the development of
      various criteria for harmonizing PET response. The novel proposed set of criteria
      called PET Residual Disease in Solid Tumor (PREDIST) seems to better distinguish
      between responder and nonresponder patients to chemoradiotherapy compared with
      the PET Response Criteria in Solid Tumors criteria. 

PMID- 24686250
TI  - Frequency and significance of physiological versus pathological uptake of 68Ga
      DOTATATE in the pancreas: validation with morphological imaging.
AB  - AIM: The objective of this study was to assess the relevance of physiological
      (68)Ga-DOTATATE PET/CT findings in the pancreas guided by morphological imaging
      (MI) in comparison with pathological tumour uptake in patients with
      neuroendocrine tumours (NETs). METHODS: A total of 138 patients with pancreatic
      NET (pNET; n=38) or non-pNET (n=100) underwent (68)Ga-DOTATATE PET/CT. Pancreatic
      regions with intensity higher than background were localized with anatomical
      reference support [head/uncinate process (HUP); body/tail (BT)] and classified as
      tumour, suspicious or physiological. Maximum standardized uptake value (SUV(max))
      was assessed in all regions. PET/CT findings were compared with MI results.
      RESULTS: Physiological uptake was seen in 10/38 pNETs (SUV(max) range, mean+/-SD
      and median in HUP and BT: 2.4-12.7, 5.9+/-3.2 and 4.6; 3.8-6.6, 6.6+/-2.5 and
      5.6, respectively). A total of 18/38 showed high uptake (SUV(max) range, mean+/
      SD and median in HUP and BT: 6.9-50, 26.9+/-13.5 and 27; 10-151, 32.2+/-36 and
      19.4, respectively) with abnormal MI results. Among 10/38 patients we observed a
      total of n=15 discordant findings between PET/CT and MI: two lesions detected by
      MI did not correspond to any pathologial uptake on PET/CT, five suspicious uptake
      in the HUP did not correspond to any abnormal finding on MI, one HUP suspicious
      uptake correspondend to a lymphadenopaty on MI and seven suspicious BT uptake
      correspondend to calcification (1/6), cystic lesions (3/6), lesion different form
      the one detected by PET/CT (1/6) or negative findings (2/6) on MI. Among the 100
      patients with non-pNETs, 97 showed homogeneous uptake and three had suspicious
      pancreatic uptake without concordant findings on MI. CONCLUSION: Physiological
      pancreatic uptake of (68)Ga-DOTATATE showed low SUV(max), whereas tumours showed
      higher SUV(max); this is in agreement with previously published data. Equivocal
      findings showed SUV(max) in the grey area between physiological and pathological
      ranges, and for these lesions MI and histological confirmation are required for
      final diagnosis.

PMID- 24686251
TI  - Large genomic rearrangements of BRCA1 and BRCA2 among patients referred for
      genetic analysis in Galicia (NW Spain): delimitation and mechanism of three novel
      BRCA1 rearrangements.
AB  - In the Iberian Peninsula, which includes mainly Spain and Portugal, large genomic
      rearrangements (LGRs) of BRCA1 and BRCA2 have respectively been found in up to
      2.33% and 8.4% of families with hereditary breast and/or ovarian cancer (HBOC)
      that lack point mutations and small indels. In Galicia (Northwest Spain), the
      spectrum and frequency of BRCA1/BRCA2 point mutations differs from the rest of
      the Iberian populations. However, to date there are no Galician frequency reports
      of BRCA1/BRCA2 LGRs. Here we used multiplex ligation-dependent probe
      amplification (MLPA) to screen 651 Galician index cases (out of the 830
      individuals referred for genetic analysis) without point mutations or small
      indels. We identified three different BRCA1 LGRs in four families. Two of them
      have been previously classified as pathogenic LGRs: the complete deletion of
      BRCA1 (identified in two unrelated families) and the deletion of exons 1 to 13.
      We also identified the duplication of exons 1 and 2 that is a LGR with unknown
      pathogenicity. Determination of the breakpoints of the BRCA1 LGRs using CNV/SNP
      arrays and sequencing identified them as NG_005905.2:g.70536_180359del,
      NG_005905.2:g.90012_97270dup, and NC_000017.10:g.41230935_41399840delinsAluSx1,
      respectively; previous observations of BRCA1 exon1-24del, exon1-2dup, and exon1
      13del LGRs have not characterized them in such detail. All the BRCA1 LGRs arose
      from unequal homologous recombination events involving Alu elements. We also
      detected, by sequencing, one BRCA2 LGR, the Portuguese founder mutation
      c.156_157insAluYa5. The low frequency of BRCA1 LGRs within BRCA1 mutation
      carriers in Galicia (2.34%, 95% CI: 0.61-7.22) seems to differ from the Spanish
      population (9.93%, 95% CI: 6.76-14.27, P-value = 0.013) and from the rest of the
      Iberian population (9.76%, 95% CI: 6.69-13.94, P-value = 0.014). 

PMID- 24686252
TI  - Investigation of the in vitro toxicological properties of the synthetic
      cannabimimetic drug CP-47,497-C8.
AB  - Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of
      cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis
      substitute since 2008. Although in the beginning CP-47,497-C8 was the main
      ingredient of "Spice" and similar products, it was partly replaced by
      aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH
      250, but never completely disappeared from the market. Since information on its
      toxicological properties is scarce, we investigated the effects of the drug in
      human derived cell lines. The cytotoxic effects were studied in a panel of assays
      (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived
      (HepG2) cell line. The strongest effects were seen in the two former assays at
      levels >= 7.5 MUM indicating that the compound interferes with protein synthesis
      and causes membrane damage. In additional comet assays, DNA damage was detected
      at levels >=10 MUM. Experiments with lesion specific enzymes showed that these
      effects are not due to oxidative damage of DNA bases. The negative findings
      obtained in Salmonella/microsome assays and the positive results of micronucleus
      tests with the cell lines indicate that the compound does not cause gene
      mutations but acts on the chromosomal level. In contrast to other synthetic
      cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in
      a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our
      findings show that the drug has only weak cytotoxic properties. However, the
      induction of chromosomal damage indicates that it may cause adverse effects in
      users due to its impact on the stability of the genetic material.

PMID- 24686253
TI  - Structural characterization and biological properties of the amyloidogenic
      elastin-like peptide (VGGVG)3.
AB  - The peculiar and unique properties of elastin are due to the abundance of
      hydrophobic residues and of repetitive sequences as XGGZG (X, Z=V, L or A).
      Unexpectedly, these sequences not only provide elasticity to the whole protein,
      but are also able to form amyloid-like fibrils. Even though amyloid fibrils have
      been associated for a long time to the development of serious disorders as
      Alzheimer's disease, recent evidence suggests that toxicity may be related to
      oligomeric species or to pre-fibrillar intermediates, rather than to mature
      fibrils. In addition, a number of studies highlighted the potential of "bio
      inspired" materials based on amyloid-like nanostructures. The present study has
      been undertaken with the aim to characterize a chemically synthesized elastin
      like peptide (VGGVG)3. Structural and biological features were compared with
      those of peptides as poly(VGGVG) and VGGVG that, having the same amino acid
      sequence, but different length and supramolecular structure have been previously
      investigated for their amyloidogenic properties. Results demonstrate that a
      minimum sequence of 15 amino acids is sufficient to aggregate into short amyloid
      like fibrils, whose formation is however strictly dependent on the specific VGGVG
      repeated sequence. Moreover, in the attempt to elucidate the relationship among
      aggregation properties, fibers morphology and biocompatibility, 3T3 fibroblasts
      were grown in the presence of VGGVG-containing elastin-like peptides (ELPs) and
      analyzed for their ability to proliferate, attach and spread on ELPs-coated
      surfaces. Data clearly show that amyloid-like fibrils made of (VGGVG)3 are not
      cytotoxic at least up to the concentration of 100 MUg/ml, even after several days
      of culture, and are a good support for cell attachment and spreading.

PMID- 24686254
TI  - Interrupted by pain: an anatomy of pain-contingent activity interruptions.

PMID- 24686255
TI  - Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of
      pain: results from a double-blind, placebo-controlled exploratory study in
      osteoarthritis of the knee.
AB  - The safety, tolerability, and efficacy of fasinumab (REGN475), a fully human
      monoclonal antibody against nerve growth factor, was evaluated for the treatment
      of pain in patients with osteoarthritis (OA) of the knee. This was a 24-week,
      double-blind, placebo-controlled, parallel-group, repeat-dose, exploratory study.
      Eligible patients 40 to 75 years of age with a diagnosis of OA of the knee and
      moderate to severe pain were randomized 1:1:1:1 to intravenous fasinumab 0.03,
      0.1, or 0.3 mg/kg or placebo and received study drug on day 1 and day 57. Pain
      intensity was recorded daily using the numeric rating scale. Safety and
      tolerability, assessed by the incidence of treatment-emergent adverse events
      (TEAEs), was the primary study endpoint. Secondary study endpoints included the
      change from baseline in daily walking knee pain and the assessment of pain,
      function, and stiffness using the Western Ontario and McMaster Osteoarthritis
      (WOMAC) index. Baseline characteristics were similar among treatment groups
      (N=217). After 24 weeks, the incidence of TEAEs ranged from 66.1% to 75.0% in the
      fasinumab groups vs. 63.6% for placebo. The most common TEAEs included
      arthralgia, hyperesthesia, myalgia, peripheral edema, and joint swelling.
      Discontinuation for TEAEs occurred in 5.6% of fasinumab patients and 3.7% of
      placebo patients. All 3 doses of fasinumab were associated with significant
      (P<.05) improvements compared with placebo in walking knee pain and WOMAC total
      and subscale scores. Fasinumab was generally well tolerated, and was associated
      with a significant reduction in walking knee pain and an improvement in function
      for up to 8 weeks.

PMID- 24686256
TI  - Rescue transoesophageal echocardiography for refractory haemodynamic instability
      during transvenous lead extraction.
AB  - AIMS: The rising number of cardiovascular implantable electronic devices has led
      to a steep increase in transvenous lead extractions (TLEs). Procedure-related,
      haemodynamically significant adverse events are uncommon during TLE yet remain an
      inevitable risk. While the use of transoesophageal echocardiography (TEE) as a
      guide to clinical decision-making during refractory circulatory instability has
      been well established, the specific utility of rescue TEE during TLE has not been
      comprehensively studied. METHODS AND RESULTS: Twenty-six patients who required
      emergent TEE to determine the aetiology of intractable haemodynamic instability
      during TLE were evaluated. Pericardial effusion requiring urgent
      pericardiocentesis and/or cardiac surgical intervention was diagnosed by TEE in
      10 patients, and progressed to cardiac arrest in 4 patients. Haemorrhagic shock
      developed in two patients suffering from femoral vein laceration and right
      haemothorax, respectively. One additional patient developed acute respiratory
      compromise and right ventricular dysfunction diagnosed by TEE, which necessitated
      prolonged post-operative intubation and inotropic therapy. In 14 patients, TEE
      excluded life-threatening cardiovascular injuries and enabled the pursuit of
      continued medical management. Two patients with reassuring TEE findings underwent
      intra-operative placement of chest tubes for pneumothorax. All the 26 patients
      were discharged from the hospital. CONCLUSION: While TLE is a relatively safe
      procedure, life-threatening cardiovascular injuries remain a rare risk. In this
      study, the use of rescue TEE ruled out significant cardiovascular injuries in the
      majority of patients. Furthermore, rescue TEE had a substantial impact on the
      efficiency of determining the aetiology of refractory haemodynamic instability
      during TLE and thereby facilitated the timely initiation of definitive
      intervention.

PMID- 24686257
TI  - Myocardial fibrosis imaging based on T1-mapping and extracellular volume fraction
      (ECV) measurement in muscular dystrophy patients: diagnostic value compared with
      conventional late gadolinium enhancement (LGE) imaging.
AB  - AIM: Cardiac involvement with progressive myocardial fibrosis leading to dilated
      cardiomyopathy is a major cause of death in muscular dystrophy patients.
      Extracellular volume fraction (ECV) measurement based on T1-mapping pre- and post
      contrast promises the detection of early 'diffuse' myocardial fibrosis that
      cannot be depicted by conventional contrast-imaging based on late gadolinium
      enhancement (LGE). With this study, we evaluated the presence of diffuse
      myocardial fibrosis in regions of 'normal' (LGE-negative) and 'diseased' (LGE
      positive) appearing myocardium as well as its relation to the extent of left
      ventricular (LV) dysfunction and the occurrence of arrhythmias in Becker muscular
      dystrophy (BMD) patients. METHODS AND RESULTS: Twenty-seven BMD patients (35 +/-
      12 years) and 17 matched male healthy controls (33 +/- 8 years) underwent
      cardiovascular magnetic resonance (CMR) studies including ECV measurement and LGE
      imaging. Ambulatory monitoring of arrhythmic events was performed by means of an
      external event loop recorder. Twenty BMD patients (74%) demonstrated cardiac
      involvement as detected by typical inferolateral presence of LGE. Twelve patients
      (44%) had an impaired LV ejection fraction-all being LGE-positive. Global
      myocardial ECV was significantly higher in the BMD group (29 +/- 6%) compared
      with the control group (24 +/- 2%, P = 0.001). Patients with cardiac involvement
      demonstrated higher global ECV (31 +/- 6%) as well as significantly increased
      regional ECV not only in LGE-positive segments (34 +/- 6%), but also in LGE
      negative segments (28 +/- 6%) compared with BMD patients without cardiac
      involvement and to controls, respectively (24 +/- 3 and 24 +/- 2%, P = 0.005).
      Global ECV in patients with cardiac involvement substantially correlated to LV
      ejection fraction (r = -0.629, P = 0.003) and to the number of LGE-positive
      segments (r = 0.783, P < 0.001). On univariable analysis, global ECV-but not the
      categorical presence of LGE per se--was significantly associated with arrhythmic
      events (OR: 1.97, CI: 32.22-1.21, P = 0.032). CONCLUSION: ECV measurement by CMR
      is a useful tool in assessing the total extent of myocardial fibrosis as well as
      in depicting subtle diffuse fibrosis in areas of normal appearing myocardium on
      LGE-images. Thus, myocardial ECV is a potential additional quantitative tool for
      accurate detection of cardiac involvement and risk stratification in muscular
      dystrophy patients.

PMID- 24686258
TI  - A baby in the heart: ALCAPA with aortic arch fistula.

PMID- 24686259
TI  - Complete and partly unexpected diagnostic findings at 18F-FDG-PET/CT scanning in
      patients with suspected prosthetic valve endocarditis.

PMID- 24686260
TI  - For what endpoint does myocardial 123I-MIBG scintigraphy have the greatest
      prognostic value in patients with chronic heart failure? Results of a pooled
      individual patient data meta-analysis.
AB  - AIMS: The purpose of this study was to determine the most appropriate prognostic
      endpoint for myocardial (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in
      patients with chronic heart failure (CHF) based on aggregate results from
      multiple studies published in the past decade. METHODS AND RESULTS: Original
      individual late (3-5 h) heart/mediastinum (H/M) ratio data of 636 CHF patients
      were retrieved from six studies from Europe and the USA. All-cause mortality,
      cardiac mortality, arrhythmic events, and heart transplantation were investigated
      to determine which provided the strongest prognostic significance for the MIBG
      imaging data. The majority of patients was male (78%), had a decreased left
      ventricular ejection fraction (31.1 +/- 12.5%), and a mean late H/M of 1.67 +/-
      0.47. During follow-up (mean 36.9 +/- 20.1 months), there were 83 deaths, 67
      cardiac deaths, 33 arrhythmic events, and 56 heart transplants. In univariate
      regression analysis, late H/M was a significant predictor of all event
      categories, but lowest hazard ratios (HRs) were for the composite endpoint of any
      event (HR = 0.30, 95% CI 0.19-0.46), all-cause (HR = 0.29, 95% CI 0.16-0.53), and
      cardiac mortality (HR = 0.28, 95% CI 0.14-0.55). In multivariate analysis, late
      H/M was an independent predictor for all event categories, except for
      arrhythmias. CONCLUSIONS: This pooled individual patient data meta-analysis
      showed that, in CHF patients, the late H/M ratio is not only useful as a
      dichotomous predictor of events (high vs. low risk), but also has prognostic
      implication over the full range of the outcome value for all event categories
      except arrhythmias.

PMID- 24686261
TI  - Barriers to life jacket use among adult recreational boaters.
AB  - OBJECTIVE: To identify barriers to life jacket use. DESIGN: Cross-sectional
      survey. SETTING: Nine public boat ramps in western Washington State, USA, August
      November, 2008. PARTICIPANTS: 675 adult boaters (>18 years) on motor boats <26
      feet long. MAIN OUTCOME: Low or no life jacket use (0-50% of time) versus high
      life jacket use (51-100% of time). RESULTS: Low/no life jacket use (0-50% of
      time) was associated with longer boat length (per foot, risk ratio [RR] 1.03, 95%
      CI 1.02 to 1.05), alcohol use (RR 1.11, 95% CI 1.01 to 1.20), perception of life
      jackets as 'uncomfortable' (RR 1.29, 95% CI 1.09 to 1.52), perceived greater
      level of swimming ability (RR 1.25, 95% CI 1.03 to 1.53 for 'expert swimmer') and
      possibly with lack of confidence that a life jacket may save one from drowning
      (RR 1.13, 95% CI 0.96 to 1.32). Low life jacket use was less likely when an
      inflatable life jacket was the primary life jacket used by a subject (RR 0.77,
      95% CI 0.63 to 0.94), a child was onboard (RR 0.88, 95% CI 0.79 to 0.99) or if
      the respondent had taken a boating safety class (RR 0.94, 95% CI 0.87 to 1.01).
      CONCLUSIONS: Life jacket use may increase with more comfortable devices, such as
      inflatable life jackets, and with increased awareness of their efficacy in
      preventing drowning. Boater education classes may be associated with increased
      life jacket use among adults.

PMID- 24686262
TI  - Children reporting rescuing other children drowning in rural Bangladesh: a
      descriptive study.
AB  - BACKGROUND: SwimSafe, a basic swimming and safer rescue curriculum, has been
      taught to large numbers of Bangladeshi children since 2006. This study examines
      the frequency and characteristics of rescues reported by children who graduated
      from SwimSafe and compares them with age-matched and sex-matched children who did
      not participate in SwimSafe. METHODS: Interviews were conducted during the
      swimming season in Raiganj, Bangladesh. Data were collected from 3890 SwimSafe
      graduates aged 6-14. Two age-matched and sex-matched controls were selected; one
      who had learned to swim naturally, the other who had not learned to swim.
      RESULTS: 188 rescues were reported by the three groups. The 12-14-year age groups
      reported the highest monthly rate of rescues (SwimSafe 10.5/100 000 (95% CI 3.4
      to 24.5), natural swimmers 8.5/100 000 (95% CI 2.2 to 21.2)) and annual rate of
      rescue reported (SwimSafe 25.4/100 000 (95% CI 13.2 to 43.9), natural swimmers
      35.4/100 000 (20.8 to 56.2)). Reported rescue numbers among both swimming groups
      was similar. Mean victim age was 4.1 years and 92.5% were under 7 years. All
      victims were younger than their rescuer (mean 5.9 years less). Most rescues
      (73.7%) took place in ponds or ditches with most (86.6%) within 10 m of the bank.
      Most victims had entered the water to bathe (53.8%). A large majority of reported
      rescues (90.9%) were conducted with the rescuer in the water, half requiring the
      rescuer to swim. CONCLUSIONS: Children report frequent drowning rescues of
      younger children in rural Bangladesh. Most reported are contact rescues with the
      rescuer in the water. Formal training for in-water rescue techniques may be
      needed to reduce the risk to the child rescuer.

PMID- 24686263
TI  - A case-control study of boat-related injuries and fatalities in Washington State.
AB  - OBJECTIVES: To identify risk factors associated with boat-related injuries and
      deaths. METHODS: We performed a case-control study using the Washington Boat
      Accident Investigation Report Database for 2003-2010. Cases were fatally injured
      boat occupants, and controls were non-fatally injured boat occupants involved in
      a boating incident. We evaluated the association between victim, boat and
      incident factors and risk of death using Poisson regression to estimate RRs and
      95% CIs. RESULTS: Of 968 injured boaters, 26% died. Fatalities were 2.6 times
      more likely to not be wearing a personal flotation device (PFD) and 2.2 times
      more likely to not have any safety features on their boat compared with those who
      survived. Boating fatalities were more likely to be in a non-motorised boat, to
      have alcohol involved in the incident, to be in an incident that involved
      capsizing, sinking, flooding or swamping, and to involve a person leaving the
      boat voluntarily, being ejected or falling than those who survived. CONCLUSIONS:
      Increasing PFD use, safety features on the boat and alcohol non-use are key
      strategies and non-motorised boaters are key target populations to prevent
      boating deaths.

PMID- 24686264
TI  - PSPs and ERPs: applying the dynamics of post-synaptic potentials to individual
      units in simulation of temporally extended Event-Related Potential reading data.
AB  - The Parallel Distributed Processing (PDP) framework is built on neural-style
      computation, and is thus well-suited for simulating the neural implementation of
      cognition. However, relatively little cognitive modeling work has concerned
      neural measures, instead focusing on behavior. Here, we extend a PDP model of
      reading-related components in the Event-Related Potential (ERP) to simulation of
      the N400 repetition effect. We accomplish this by incorporating the dynamics of
      cortical post-synaptic potentials--the source of the ERP signal--into the model.
      Simulations demonstrate that application of these dynamics is critical for model
      elicitation of repetition effects in the time and frequency domains. We conclude
      that by advancing a neurocomputational understanding of repetition effects, we
      are able to posit an interpretation of their source that is both explicitly
      specified and mechanistically different from the well-accepted cognitive one.

PMID- 24686265
TI  - Hepatocellular carcinoma: sorafenib: for once age is not an issue.
AB  - Are some patients with hepatocellular carcinoma just too old to be treated? More
      specifically, should the age of a patient influence the way sorafenib is
      prescribed? A new study has tried to address these questions, providing helpful
      information to guide clinicians making these decisions.

PMID- 24686266
TI  - Management of portal vein thrombosis in liver cirrhosis.
AB  - Portal vein thrombosis (PVT) is a fairly common complication of liver cirrhosis.
      Importantly, occlusive PVT might influence the prognosis of patients with
      cirrhosis. Evidence from a randomized controlled trial has shown that
      anticoagulation can prevent the occurrence of PVT in patients with cirrhosis
      without prior PVT. Evidence from several case series has also demonstrated that
      anticoagulation can achieve portal vein recanalization in patients with cirrhosis
      and PVT. Early initiation of anticoagulation therapy and absence of previous
      portal hypertensive bleeding might be positively associated with a high rate of
      portal vein recanalization after anticoagulation. However, the possibility of
      spontaneous resolution of partial PVT questions the necessity of anticoagulation
      for the treatment of partial PVT. In addition, a relatively low recanalization
      rate of complete PVT after anticoagulation therapy suggests its limited
      usefulness in patients with complete PVT. Successful insertion of a transjugular
      intrahepatic portosystemic shunt (TIPS) not only recanalizes the thrombosed
      portal vein, but also relieves the symptomatic portal hypertension. However, the
      technical difficulty of TIPS potentially limits its widespread application, and
      the risk and benefits should be fully balanced. Notably, current recommendations
      regarding the management of PVT in liver cirrhosis are insufficient owing to low
      quality evidence. 

PMID- 24686267
TI  - Optimal bowel preparation--a practical guide for clinicians.
AB  - High-quality bowel preparation is essential for effective colonoscopy. Bowel
      preparations are judged by their safety, efficacy and tolerability. Between
      efficacy and tolerability, efficacy is the clinical priority because inadequate
      preparations are disruptive and costly. Achieving high rates of adequate
      preparation depends first on using split-dose or same-day dosing. Patients who
      have medical predictors of inadequate preparation quality (for example chronic
      constipation) should be prescribed more aggressive preparations and patients who
      have factors that predict they are less likely to follow the instructions (such
      as English not being their first language) should receive intensified education.
      On the day of the procedure, patients with persistent brown effluent should be
      considered for large-volume enemas or additional oral preparation before
      proceeding with colonoscopy. During the procedure, preparation quality should be
      graded after the clean-up has been completed. 

PMID- 24686269
TI  - Hepatocellular carcinoma: low risk of HCC in patients who have PSC and cirrhosis.
AB  - Primary sclerosing cholangitis (PSC) is understood to be associated with an
      increased risk of malignancy in the bile ducts, gallbladder and colon. The risk
      of hepatocellular carcinoma in the setting of PSC, however, is not well defined.
      Zenouzi et al. provide an analysis of their experience in a recent article.

PMID- 24686270
TI  - Management of hepatitis B during pregnancy.
AB  - Chronic HBV infection is estimated to affect >350 million people worldwide and
      represents a substantial source of morbidity and mortality related to cirrhosis
      and hepatocellular carcinoma. Mother-to-child transmission (MTCT) remains an
      important source of incident cases of hepatitis B. Immunoprophylaxis of infants
      born to mothers who are positive for hepatitis B surface antigen is used to
      prevent MTCT; however, under-utilization of this intervention in certain regions
      endemic for HBV infection and failure of immunoprophylaxis in 5-10% of cases are
      barriers to preventing HBV transmission via this route. Data suggest that a high
      level of HBV viraemia in pregnant women is a substantial risk factor for
      immunoprophylaxis failure. Potential means of reducing viral load include
      antiviral therapy in the third trimester to reduce exposure of the neonate to the
      virus. Determining the optimal time to treat active HBV-related liver disease in
      women who wish to become pregnant, as well as managing antiviral therapy in
      patients who become pregnant, remains challenging. Owing to the vulnerable
      population affected by these issues, clinical trials are difficult and, thus,
      evidence-based recommendations are limited. Emerging data are addressing
      management of HBV during pregnancy that health-care providers should be made
      aware of. Here, we provide an overview of issues pertinent to HBV infection
      during pregnancy and present a management algorithm. 

PMID- 24686268
TI  - Radiation enteropathy--pathogenesis, treatment and prevention.
AB  - Changes in cancer incidence and mortality have been modest during the past
      several decades, but the number of cancer survivors has almost tripled during the
      same period. With an increasing cohort of cancer survivors, efforts to prevent,
      diagnose and manage adverse effects of cancer therapy, in general, and those of
      radiation therapy specifically, have intensified. Many cancer survivors have
      undergone radiation therapy of tumours in the pelvis or abdomen, thus rendering
      the bowel at risk of injury. In fact, the current prevalence of patients who have
      long-term radiation-induced intestinal adverse effects exceeds that of IBD.
      Considerable progress towards reducing toxicity of radiation therapy has been
      made by the introduction of so-called dose-sculpting treatment techniques, which
      enable precise delivery of the radiation beam. Moreover, new insights into the
      underlying pathophysiology have resulted in an improved understanding of
      mechanisms of radiation-induced bowel toxicity and in development of new
      diagnostic strategies and management opportunities. This Review discusses the
      pathogenesis of early and delayed radiation-induced bowel toxicity, presents
      current management options and outlines priorities for future research. By adding
      insight into molecular and cellular mechanisms of related bowel disorders,
      gastroenterologists can substantially strengthen these efforts. 

PMID- 24686271
TI  - Texts and images.

PMID- 24686272
TI  - Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T
      cells and natural killer cells in healthy volunteers.
AB  - Low-dose interleukin-2 (IL-2) expands regulatory T cells (Tregs) and natural
      killer (NK) cells after stem cell transplantation (SCT) and may reduce graft
      versus-host disease (GVHD). We hypothesized that ultra-low dose (ULD) IL-2 could
      serve as an immune-modulating agent for stem cell donors to prevent GVHD
      following SCT. However, the safety, dose level, and immune signatures of ULD IL-2
      in immune-competent healthy subjects remain unknown. Here, we have characterized
      the phenotype and function of Tregs and NK cells as well as the gene expression
      and cytokine profiles of 21 healthy volunteers receiving 50,000 to 200,000
      units/m(2)/day IL-2 for 5 days. ULD IL-2 was well tolerated and induced a
      significant increase in the frequency of Tregs with increased suppressive
      function. There was a marked expansion of CD56(bright) NK cells with enhanced
      interferon-gamma (IFN-gamma) production. Serum cytokine profiling demonstrated
      increase of IFN-gamma induced protein 10 (IP-10). Gene expression analysis
      revealed significant changes in a highly restricted set of genes, including
      FOXP3, IL-2RA, and CISH. This is the first study to evaluate global immune
      modulating function of ULD IL-2 in healthy subjects and to support the future
      studies administrating ULD IL-2 to stem cell donors. 

PMID- 24686273
TI  - Synaptosomal lactate dehydrogenase isoenzyme composition is shifted toward
      aerobic forms in primate brain evolution.
AB  - With the evolution of a relatively large brain size in haplorhine primates (i.e.
      tarsiers, monkeys, apes, and humans), there have been associated changes in the
      molecular machinery that delivers energy to the neocortex. Here we investigated
      variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of
      the neocortex and striatum in primates using quantitative Western blotting and
      isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of
      isoform expression revealed that LDH in synaptosomal fractions from both
      forebrain regions shifted towards a predominance of the heart-type, aerobic
      isoform LDH-B among haplorhines as compared to strepsirrhines (i.e. lorises and
      lemurs), while in the total homogenate of the neocortex and striatum there was no
      significant difference in LDH isoenzyme composition between the primate
      suborders. The largest increase occurred in synapse-associated LDH-B expression
      in the neocortex, with an especially remarkable elevation in the ratio of LDH
      B/LDH-A in humans. The phylogenetic variation in the ratio of LDH-B/LDH-A was
      correlated with species-typical brain mass but not the encephalization quotient.
      A significant LDH-B increase in the subneuronal fraction from haplorhine
      neocortex and striatum suggests a relatively higher rate of aerobic glycolysis
      that is linked to synaptosomal mitochondrial metabolism. Our results indicate
      that there is a differential composition of LDH isoenzymes and metabolism in
      synaptic terminals that evolved in primates to meet increased energy requirements
      in association with brain enlargement.

PMID- 24686274
TI  - Qudit-teleportation for photons with linear optics.
AB  - Quantum Teleportation, the transfer of the state of one quantum system to another
      without direct interaction between both systems, is an important way to transmit
      information encoded in quantum states and to generate quantum correlations
      (entanglement) between remote quantum systems. So far, for photons, only
      superpositions of two distinguishable states (one "qubit") could be teleported.
      Here we show how to teleport a "qudit", i.e. a superposition of an arbitrary
      number d of distinguishable states present in the orbital angular momentum of a
      single photon using d beam splitters and d additional entangled photons. The same
      entanglement resource might also be employed to collectively teleport the state
      of d/2 photons at the cost of one additional entangled photon per qubit. This is
      superior to existing schemes for photonic qubits, which require an additional
      pair of entangled photons per qubit. 

PMID- 24686275
TI  - Clinical management of food protein-induced enterocolitis syndrome.
AB  - PURPOSE OF REVIEW: The article discusses the clinical management of patients
      affected by food protein-induced enterocolitis syndrome (FPIES), focusing on
      established therapeutic choices and future options. RECENT FINDINGS: After FPIES
      has been diagnosed and avoidance of the culprit food prescribed, the most
      important management needs are as follows. First, recurrence of acute FPIES
      episodes due to accidental ingestion of culprit food. It may be useful to give
      patients' families an action plan. The principal suggested treatments are
      intravenous fluids and steroids, whereas the use of epinephrine and ondansetron
      requires further study. In mild-to-moderate cases, oral rehydration should be
      sufficient. Second, dietary introduction of at-risk foods. In children with
      FPIES, in addition to that/those identified as culprit(s), some foods may not be
      tolerated (typically cow's milk, legumes, cereals, poultry). It has been
      suggested to avoid introducing these foods during the baby's first year.
      Otherwise, they may be given for the first time in hospital, performing an oral
      food challenge. Third, acquisition of tolerance. Children affected by cow's milk
      FPIES have a good chance of acquiring tolerance by the time they reach age 18-24
      months. For other culprit foods, insufficient data are available to indicate the
      appropriate time, so that it is suggested that an oral food challenge be
      performed about 1  year after the last acute episode. SUMMARY: Future clinical
      management of FPIES must take into account, among other factors, improved
      understanding of pathogenesis, possible detection of different phenotypes, and
      the introduction of more effective therapies for acute episodes. These factors
      will undoubtedly influence management decisions, which will become more
      diversified and effective.

PMID- 24686276
TI  - Definition, etiology, and diagnosis of food protein-induced enterocolitis
      syndrome.
AB  - PURPOSE OF REVIEW: Food protein-induced enterocolitis syndrome (FPIES) is a
      poorly understood non-IgE-mediated food hypersensitivity, primarily affecting
      infants and toddlers. There are few data regarding pathophysiology of FPIES that
      suggest local intestinal imbalance between TNF-alpha and TGF-beta. Patients
      frequently present with multiple reactions, which are characterized by
      projectile, repetitive emesis, dehydration, lethargy, and failure to thrive.
      Despite the severity of presentation, the diagnosis is frequently delayed, and
      patients often undergo extensive and invasive evaluation prior to reaching the
      diagnosis. RECENT FINDINGS: Reviews published in the last year provide a general
      approach to diagnosis and management of FPIES and aim to increase awareness and
      understanding of FPIES among general pediatricians. SUMMARY: Multicenter studies
      are necessary to reevaluate and modify the oral food challenge criteria. Research
      on the pathophysiology of FPIES reactions is necessary to provide insight into
      the evidence-based approach to diagnosis and management of FPIES. Registries are
      needed to understand the phenotype, triggers, and prevalence of FPIES.

PMID- 24686277
TI  - Epidemiology of food protein-induced enterocolitis syndrome.
AB  - PURPOSE OF REVIEW: To summarize the epidemiology of food protein-induced
      enterocolitis syndrome (FPIES). RECENT FINDINGS: FPIES is regarded as a rare non
      IgE-mediated gastrointestinal allergic disorder. Older nonpopulation-based
      studies reported an average of 1-15 cases presenting to allergy clinics a year,
      but recent studies have reported figures as high as 90 cases a year. The yearly
      incidence of FPIES in one Australian study was one in 10,000 infants less than 2
      years of age. Chronic FPIES typically presents in neonates, whereas acute FPIES
      is primarily a disorder of young infants. FPIES has a slight male predominance;
      eczema and a family history of atopy are commonly present at diagnosis; almost
      one in 10 infants have coexistent IgE food allergies and siblings are rarely
      affected. There is regional variation in common triggering foods, rates of
      combined cow milk and soy FPIES and multiple food group FPIES. Understanding of
      the epidemiology of FPIES is limited by the lack of a universally accepted
      definition and the publication of few prospective population-based case series.
      SUMMARY: FPIES is not as rare as once thought, but how common it is, what factors
      predispose to its development, and why there is regional variation needs to be
      addressed by future well designed population-based studies?

PMID- 24686279
TI  - Full-reference quality estimation for images with different spatial resolutions.
AB  - Multimedia communication is becoming pervasive because of the progress in
      wireless communications and multimedia coding. Estimating the quality of the
      visual content accurately is crucial in providing satisfactory service. State of
      the art visual quality assessment approaches are effective when the input image
      and reference image have the same resolution. However, finding the quality of an
      image that has spatial resolution different than that of the reference image is
      still a challenging problem. To solve this problem, we develop a quality
      estimator (QE), which computes the quality of the input image without resampling
      the reference or the input images. In this paper, we begin by identifying the
      potential weaknesses of previous approaches used to estimate the quality of
      experience. Next, we design a QE to estimate the quality of a distorted image
      with a lower resolution compared with the reference image. We also propose a
      subjective test environment to explore the success of the proposed algorithm in
      comparison with other QEs. When the input and test images have different
      resolutions, the subjective tests demonstrate that in most cases the proposed
      method works better than other approaches. In addition, the proposed algorithm
      also performs well when the reference image and the test image have the same
      resolution. 

PMID- 24686278
TI  - Natural history of food protein-induced enterocolitis syndrome.
AB  - PURPOSE OF REVIEW: Because of the paucity of reports and variability in the
      diagnostic criteria utilized, little is known regarding the natural outcome of
      patients with food protein-induced enterocolitis syndrome (FPIES). Data extracted
      from referenced manuscripts, as well as allergists' unpublished observations from
      across the globe, were used to form a cohesive opinion regarding its natural
      outcome. RECENT FINDINGS: All authors concur that there is a generally high rate
      of recovery for FPIES. The most common foods causing FPIES are milk and soy.
      Depending upon which study is analyzed, by the age of 3-5 years, approximately
      90% of patients recover from their disease. Recovery from FPIES to solid foods,
      occurs at a later age, but may reflect a later stage of introduction of the food
      into the diet. An important clinical outcome, although not common, is a shift
      from FPIES food hypersensitivity to an IgE-mediated food allergy. This
      necessitates a change in the oral food challenge protocol, if IgE-mediated
      sensitization is detected. SUMMARY: Over the past several years, there has been
      an increasing awareness of FPIES. This knowledge should lead to a more timely
      diagnosis and should reassure parents and practitioners alike regarding its
      favorable course.

PMID- 24686280
TI  - Robust object tracking via sparse collaborative appearance model.
AB  - In this paper, we propose a robust object tracking algorithm based on a sparse
      collaborative model that exploits both holistic templates and local
      representations to account for drastic appearance changes. Within the proposed
      collaborative appearance model, we develop a sparse discriminative classifier
      (SDC) and sparse generative model (SGM) for object tracking. In the SDC module,
      we present a classifier that separates the foreground object from the background
      based on holistic templates. In the SGM module, we propose a histogram-based
      method that takes the spatial information of each local patch into consideration.
      The update scheme considers both the most recent observations and original
      templates, thereby enabling the proposed algorithm to deal with appearance
      changes effectively and alleviate the tracking drift problem. Numerous
      experiments on various challenging videos demonstrate that the proposed tracker
      performs favorably against several state-of-the-art algorithms.

PMID- 24686281
TI  - Gaussian Copula multivariate modeling for texture image retrieval using wavelet
      transforms.
AB  - In the framework of texture image retrieval, a new family of stochastic
      multivariate modeling is proposed based on Gaussian Copula and wavelet
      decompositions. We take advantage of the copula paradigm, which makes it possible
      to separate dependence structure from marginal behavior. We introduce two new
      multivariate models using, respectively, generalized Gaussian and Weibull
      densities. These models capture both the subband marginal distributions and the
      correlation between wavelet coefficients. We derive, as a similarity measure, a
      closed form expression of the Jeffrey divergence between Gaussian copula-based
      multivariate models. Experimental results on well-known databases show
      significant improvements in retrieval rates using the proposed method compared
      with the best known state-of-the-art approaches.

PMID- 24686282
TI  - Unsupervised post-nonlinear unmixing of hyperspectral images using a Hamiltonian
      Monte Carlo algorithm.
AB  - This paper presents a nonlinear mixing model for hyperspectral image unmixing.
      The proposed model assumes that the pixel reflectances are post-nonlinear
      functions of unknown pure spectral components contaminated by an additive white
      Gaussian noise. These nonlinear functions are approximated using second-order
      polynomials leading to a polynomial post-nonlinear mixing model. A Bayesian
      algorithm is proposed to estimate the parameters involved in the model yielding
      an unsupervised nonlinear unmixing algorithm. Due to the large number of
      parameters to be estimated, an efficient Hamiltonian Monte Carlo algorithm is
      investigated. The classical leapfrog steps of this algorithm are modified to
      handle the parameter constraints. The performance of the unmixing strategy,
      including convergence and parameter tuning, is first evaluated on synthetic data.
      Simulations conducted with real data finally show the accuracy of the proposed
      unmixing strategy for the analysis of hyperspectral images. 

PMID- 24686283
TI  - Nonlinear transform for robust dense block-based motion estimation.
AB  - We present a noniterative multiresolution motion estimation strategy, involving
      block-based comparisons in each detail band of a Laplacian pyramid. A novel
      matching score is developed and analyzed. The proposed matching score is based on
      a class of nonlinear transformations of Laplacian detail bands, yielding 1-bit or
      2-bit representations. The matching score is evaluated in a dense full-search
      motion estimation setting, with synthetic video frames and an optical flow data
      set. Together with a strategy for combining the matching scores across
      resolutions, the proposed method is shown to produce smoother and more robust
      estimates than mean square error (MSE) in each detail band and combined. It
      tolerates more of nontranslational motion, such as rotation, validating the
      analysis, while providing much better localization of the motion discontinuities.
      We also provide an efficient implementation of the motion estimation strategy and
      show that the computational complexity of the approach is closely related to the
      traditional MSE block-based full-search motion estimation procedure.

PMID- 24686284
TI  - Studying food reward and motivation in humans.
AB  - A key challenge in studying reward processing in humans is to go beyond
      subjective self-report measures and quantify different aspects of reward such as
      hedonics, motivation, and goal value in more objective ways. This is particularly
      relevant for the understanding of overeating and obesity as well as their
      potential treatments. In this paper are described a set of measures of food
      related motivation using handgrip force as a motivational measure. These methods
      can be used to examine changes in food related motivation with metabolic
      (satiety) and pharmacological manipulations and can be used to evaluate
      interventions targeted at overeating and obesity. However to understand food
      related decision making in the complex food environment it is essential to be
      able to ascertain the reward goal values that guide the decisions and behavioral
      choices that people make. These values are hidden but it is possible to ascertain
      them more objectively using metrics such as the willingness to pay and a method
      for this is described. Both these sets of methods provide quantitative measures
      of motivation and goal value that can be compared within and between individuals.

PMID- 24686285
TI  - Metabolic flux analysis of Escherichia coli knockouts: lessons from the Keio
      collection and future outlook.
AB  - Cellular metabolic and regulatory systems are of fundamental interest to
      biologists and engineers. Incomplete understanding of these complex systems
      remains an obstacle to progress in biotechnology and metabolic engineering. An
      established method for obtaining new information on network structure, regulation
      and dynamics is to study the cellular system following a perturbation such as a
      genetic knockout. The Keio collection of all viable Escherichia coli single-gene
      knockouts is facilitating a systematic investigation of the regulation and
      metabolism of E. coli. Of all omics measurements available, the metabolic flux
      profile (the fluxome) provides the most direct and relevant representation of the
      cellular phenotype. Recent advances in (13)C-metabolic flux analysis are now
      permitting highly precise and accurate flux measurements for investigating
      cellular systems and guiding metabolic engineering efforts. 

PMID- 24686287
TI  - Coffee, Cake & Culture: Evaluation of an art for health programme for older
      people in the community.
AB  - Arts for health initiatives and networks are being developed in a number of
      countries and an international literature is emerging on the evidence of their
      benefits to people's health, wellbeing and quality of life. Engagement in
      cultural and creative arts by older people can increase their morale and self
      confidence and provides opportunities for social connection. Museums and
      galleries are increasingly required to justify their expenditure, reach and
      impact and some are working in partnership with local councils, hospitals,
      schools and communities to improve access to their collections. There is a body
      of literature emerging that describes such initiatives but empirical evidence of
      their benefits is less developed. This article reports an evaluation of an art
      for health initiative - Coffee, Cake & Culture organised and delivered by
      Whitworth Art Gallery and Manchester Museum in 2012 for older people living in a
      care home and a supported living facility. The study has identified the benefits
      and impacts of the arts for health programme and its feasibility for older
      people, with or without diagnosed memory loss - dementia, living in a care home
      or supported living facility and their care staff. The findings demonstrate there
      were benefits to the older people and their care staff in terms of wellbeing,
      social engagement, learning, social inclusion and creativity. These benefits were
      immediate and continued in the short term on their return home. The majority of
      older people and care staff had not previously been to the art gallery or museum
      and the programme encouraged creative arts and cultural appreciation which
      promoted social inclusion, wellbeing and quality of life. The programme is
      feasible and important lessons were identified for future planning. Further
      research involving partnerships of researchers, arts for health curators,
      artists, care staff, older people and their families is warranted. 

PMID- 24686286
TI  - From genomes to societies: a holistic view of determinants of human health.
AB  - Both biological and social sciences have identified contributing factors to human
      health. However, health outcomes are unlikely to equal a simple sum of these
      identified factors. This article makes an attempt to put together the
      information, methods, and technologies that relate to health outcomes from
      biological, behavioral, and social disciplines. Much of this information was
      obtained by controlling for the variations of the factors in 'other' disciplines.
      For example, genetic factors were controlled for in identifying the behavioral
      determinants of health. Looking forward, better understandings of health outcomes
      may require exploiting the interactions of health determinants that were
      identified from different disciplines. We propose the concept of 'systems health'
      studies, which take health outcomes as the outputs of a system, where the inputs
      and their interactions from multiple disciplines are considered. 

PMID- 24686288
TI  - Temporal bone changes in patients with Goldenhar syndrome with special emphasis
      on inner ear abnormalities.
AB  - OBJECTIVE: Goldenhar syndrome is a developmental disorder presenting with
      orofacial and vertebral anomalies, which are also accompanied by abnormalities in
      other organs. We examined temporal bone changes with special emphasis on inner
      ear abnormalities in these patients. STUDY DESIGN: A retrospective review of 7
      new cases in addition to a previously published series of 14 cases with
      clinically diagnosed Goldenhar syndrome was carried out to search for inner ear
      anomalies. In addition, temporal bone imaging studies from the literature were
      summarized and compared with our results. SETTING: Departments of Neuroradiology
      and Otorhinolaryngology at a university hospital. PATIENTS: In addition to the
      previous series of 14 patients, 7 new patients with Goldenhar syndrome were
      identified. INTERVENTIONS: Patients underwent otologic examination, audiometric
      studies, and high-resolution computed tomography (CT) or magnetic resonance
      imaging (MRI) of the temporal bone. MAIN OUTCOME MEASURE: Temporal bone changes
      and specifically inner ear malformations. RESULTS: Nineteen of 21 patients showed
      changes of the external and middle ear correlating with the literature. Seven of
      21 patients showed inner ear abnormalities constituting one-third of all
      patients. These ranged from mild such as vestibular enlargement to severe defects
      such as cochlear hypoplasia and common cavity. CONCLUSION: Inner ear
      abnormalities were present in one-third of patients. Although in some cases,
      these might not be of clinical significance, some patients show severe defects of
      the inner ear requiring more complex hearing loss therapy. Therefore, imaging of
      the temporal bone structures is important in the care of these patients.

PMID- 24686289
TI  - Histopathologic changes in the cochlea associated with diabetes mellitus--a
      review.
AB  - BACKGROUND: The pathologic changes that occur as a result of diabetic
      microangiopathy have been well described for the kidneys and the eyes. Although
      many studies suggest an association between diabetes mellitus and hearing loss,
      the pathologic changes in the cochlea in association with the diabetic state
      remain to be clarified. AIM/OBJECTIVE: The aim of this review is to determine the
      effects of diabetes mellitus on cochlear morphology. METHOD: A comprehensive
      search for relevant articles was carried out on electronic databases of Ovid
      Medline, Ovid Medline in Process, PubMed, Ovid Embase,or Biosis Preview, The
      Cochrane Library, ISI Web of Science, and Scopus. Articles published in English
      between 1940 and June 2010 were eligible to be reviewed. Using predefined
      inclusion criteria, published articles on histologic changes occurring in the
      cochlea due to diabetes mellitus were selected and reviewed, and their findings
      were synthesized. RESULTS: Changes were observed in the basement membrane of the
      capillaries of the stria vascularis and in the basilar membrane, which was
      remarkably thickened, giving rise to diabetic microangiopathy. Loss of spiral
      ganglion neurons, organ of Corti cells, and atrophic changes in the stria
      vascularis were varied and infrequent. CONCLUSION: There seems to be variable
      vulnerability of different cochlear cell types to the DM state. Further studies
      are required to determine the factors responsible for the differences in the
      histopathologic observations of cochlear tissues.

PMID- 24686290
TI  - Outcomes of different laser types in laser-assisted stapedotomy: a systematic
      review.
AB  - OBJECTIVE: To assess hearing results and complications following primary
      stapedotomy in otosclerosis patients, comparing different laser types. DATA
      SOURCES: Pubmed, Embase, The Cochrane Library, CINAHL, and Scopus. STUDY
      SELECTION: A systematic bibliographic search was conducted to identify all
      original articles, comparing hearing outcome between different lasers used for
      fenestration in stapedotomy. DATA EXTRACTION: Directness of evidence and risk of
      bias of the selected articles were assessed. Studies with low or moderate
      directness of evidence, or high risk of bias, were not further analyzed. DATA
      SYNTHESIS: The absolute risks, risk differences, and 95% confidence intervals
      were extracted only for the studies with high directness of evidence and moderate
      to low risk of bias. CONCLUSION: A total of 383 unique articles were retrieved.
      Four studies provided direct evidence, whereas all studies carried moderate to
      high risk of bias. After exclusion of the studies that did not provide direct
      evidence and/or carried high risk of bias, 2 studies were considered eligible for
      data extraction. This best available evidence shows a slightly better air-bone
      gap closure for CO2 laser compared to potassium titanyl phosphate laser, but the
      clinical relevance is unclear. The risk difference of 28.1% [95% confidence
      interval, 22.8, 33.4] between CO2 and erbium yttrium aluminium garnet favors CO2
      laser. Unfortunately, this current best available evidence is insufficient to
      draw any definitive conclusions on which laser to use for fenestration in
      stapedotomy.

PMID- 24686291
TI  - The factors associated with tumor stability observed with conservative management
      of intracanalicular vestibular schwannoma.
AB  - OBJECTIVE: Periodic observation with imaging is an acceptable option for patients
      with small vestibular schwannomas (VSs). The objective of this study was to
      evaluate the outcome of conservative management of intracanalicular VSs (ICVSs).
      METHODS: We reviewed 31 patients who were followed up for more than 1 year among
      patients diagnosed as having VS limited to the internal auditory canal. The
      median follow-up period was 31 months (range, 12-84 mo). We analyzed the
      patients' clinical features, clinical courses, and audiologic changes. RESULTS:
      The most frequent initial presenting symptom in patients with ICVS was hearing
      loss, and one-half of the patients (8 of 16) had a history of sudden hearing
      loss. Seven patients (22.5%) showed tumor growth during the follow-up period.
      When we considered the initial tumor size in ICVS, the patients larger in size
      than the median showed a significantly higher rate of tumor growth. In terms of
      the initial hearing levels of ICVS according to the Consensus Meeting Guidelines,
      five patients were classified as Class A (normal hearing) and six patients were
      classified as Class B. Only one patient among patients with useful hearing
      (Classes A and B) showed tumor growth. The follow-up hearing levels of all Class
      A patients were preserved; however, all Class B patients deteriorated to Class C.
      CONCLUSION: Patients with ICVS showed favorable results with conservative
      management. Among them, patients with small tumors and normal hearing showed a
      good prognosis.

PMID- 24686292
TI  - Multivariable dynamic ankle mechanical impedance with relaxed muscles.
AB  - Neurological or biomechanical disorders may distort ankle mechanical impedance
      and thereby impair locomotor function. This paper presents a quantitative
      characterization of multivariable ankle mechanical impedance of young healthy
      subjects when their muscles were relaxed, to serve as a baseline to compare with
      pathophysiological ankle properties of biomechanically and/or neurologically
      impaired patients. Measurements using a highly backdrivable wearable ankle robot
      combined with multi-input multi-output stochastic system identification methods
      enabled reliable characterization of ankle mechanical impedance in two degrees-of
      freedom (DOFs) simultaneously, the sagittal and frontal planes. The
      characterization included important ankle properties unavailable from single DOF
      studies: coupling between DOFs and anisotropy as a function of frequency. Ankle
      impedance in joint coordinates showed responses largely consistent with a second
      order system consisting of inertia, viscosity, and stiffness in both seated (knee
      flexed) and standing (knee straightened) postures. Stiffness in the sagittal
      plane was greater than in the frontal plane and furthermore, was greater when
      standing than when seated, most likely due to the stretch of bi-articular muscles
      (medial and lateral gastrocnemius). Very low off-diagonal partial coherences
      implied negligible coupling between dorsiflexion-plantarflexion and inversion
      eversion. The directions of principal axes were tilted slightly counterclockwise
      from the original joint coordinates. The directional variation (anisotropy) of
      ankle impedance in the 2-D space formed by rotations in the sagittal and frontal
      planes exhibited a characteristic "peanut" shape, weak in inversion-eversion over
      a wide range of frequencies from the stiffness dominated region up to the inertia
      dominated region. Implications for the assessment of neurological and
      biomechanical impairments are discussed. 

PMID- 24686294
TI  - Autophagy researchers.

PMID- 24686293
TI  - Changes in memory before and after stroke differ by age and sex, but not by race.
AB  - BACKGROUND: Post-stroke memory impairment is more common among older adults,
      women and blacks. It is unclear whether post-stroke differences reflect
      differential effects of stroke per se or differences in prestroke functioning. We
      compare memory trajectories before and after stroke by age, sex and race.
      METHODS: Health and Retirement Study participants aged >=50 years (n = 17,341),
      with no stroke history at baseline, were interviewed biennially up to 10 years
      for first self- or proxy-reported stroke (n = 1,574). Segmented linear regression
      models were used to compare annual rates of memory change before and after stroke
      among 1,169 stroke survivors, 405 stroke decedents and 15,767 stroke-free
      participants. Effect modification was evaluated with analyses stratified by
      baseline age (<=70 vs. >70), sex and race (white vs. nonwhite), and using
      interaction terms between age/sex/race indicators and annual memory change.
      RESULTS: Older (>70 years) adults experienced a faster memory decline before
      stroke (-0.19 vs. -0.10 points/year for survivors, -0.24 vs. -0.13 points/year
      for decedents, p < 0.001 for both interactions), and among stroke survivors,
      larger memory decrements (-0.64 vs. -0.26 points, p < 0.001) at stroke and faster
      memory decline (-0.15 vs. -0.07 points/year, p = 0.003) after stroke onset,
      compared to younger adults. Female stroke survivors experienced a faster
      prestroke memory decline than male stroke survivors (-0.14 vs. -0.10 points/year,
      p < 0.001). However, no sex differences were seen for other contrasts. Although
      whites had higher post-stroke memory scores than nonwhites, race was not
      associated with rate of memory decline during any period of time; i.e. race did
      not significantly modify the rate of decline before or after stroke or the
      immediate effect of stroke on memory. CONCLUSIONS: Older age predicted worse
      memory change before, at and after stroke onset. Sex and race differences in post
      stroke memory outcomes might be attributable to prestroke disparities, which may
      be unrelated to cerebrovascular disease.

PMID- 24686295
TI  - A simple stimulatory device for evoking point-like tactile stimuli: a searchlight
      for LFP to spike transitions.
AB  - Current neurophysiological research has the aim to develop methodologies to
      investigate the signal route from neuron to neuron, namely in the transitions
      from spikes to Local Field Potentials (LFPs) and from LFPs to spikes. LFPs have a
      complex dependence on spike activity and their relation is still poorly
      understood(1). The elucidation of these signal relations would be helpful both
      for clinical diagnostics (e.g. stimulation paradigms for Deep Brain Stimulation)
      and for a deeper comprehension of neural coding strategies in normal and
      pathological conditions (e.g. epilepsy, Parkinson disease, chronic pain). To this
      aim, one has to solve technical issues related to stimulation devices,
      stimulation paradigms and computational analyses. Therefore, a custom-made
      stimulation device was developed in order to deliver stimuli well regulated in
      space and time that does not incur in mechanical resonance. Subsequently, as an
      exemplification, a set of reliable LFP-spike relationships was extracted. The
      performance of the device was investigated by extracellular recordings, jointly
      spikes and LFP responses to the applied stimuli, from the rat Primary
      Somatosensory cortex. Then, by means of a multi-objective optimization strategy,
      a predictive model for spike occurrence based on LFPs was estimated. The
      application of this paradigm shows that the device is adequately suited to
      deliver high frequency tactile stimulation, outperforming common piezoelectric
      actuators. As a proof of the efficacy of the device, the following results were
      presented: 1) the timing and reliability of LFP responses well match the spike
      responses, 2) LFPs are sensitive to the stimulation history and capture not only
      the average response but also the trial-to-trial fluctuations in the spike
      activity and, finally, 3) by using the LFP signal it is possible to estimate a
      range of predictive models that capture different aspects of the spike activity. 

PMID- 24686297
TI  - Evaluation of a systematic approach to pediatric back pain: the utility of
      magnetic resonance imaging.
AB  - BACKGROUND: Several studies have suggested that back pain in the majority of
      pediatric patients does not have an identifiable cause. Many children undergo
      extensive diagnostic workup that ultimately results in a nonconfirmative
      diagnosis. The purpose of this study was to (1) describe the prevalence of back
      pain seen in a pediatric orthopaedic clinic; (2) evaluate the efficacy of a
      systematic approach dependent on magnetic resonance imaging (MRI) in the
      diagnosis of pediatric back pain; and (3) analyze sensitivity, specificity,
      positive predictive value, and negative predictive value of various clinical
      signs and symptoms. METHODS: For a 24-month period, all patients that presented
      with a chief complaint of back pain were prospectively enrolled in this study and
      evaluated in a systematic approach which utilized MRI for patients with constant
      pain, night pain, radicular pain, or abnormal neurological examination after an
      initial history, physical examination, and negative radiographic examination.
      RESULTS: The prevalence of chief complaint of back pain was 8.6% (261/3042
      patients). Of the 261 patients, 34% had an identifiable pathology following the
      systematic approach. In 8.8% of patients, the diagnosis was established with the
      history, physical examination, and plain radiographs. MRI yielded a definitive
      diagnosis in another 25% of patients. It is noteworthy that of the 89 patients
      with a confirmed pathology, 26% were identified with plain radiographs and 74%
      with MRI. CONCLUSIONS: A systematic approach to diagnose pediatric back pain
      demonstrated that 34% of pediatric patients that present to an outpatient
      orthopaedic clinic complaining of back pain will have identifiable pathology. The
      diagnostic yield increased from 8.8% with the history, physical examination, and
      plain radiographs to 22% with the TCN Bone Scan to 36% with the use of the MRI.
      The clinician should be aware that the presences of lumbar pain or constant pain
      are red flags for the presence of underlying pathology. LEVEL OF EVIDENCE: Level
      III.

PMID- 24686298
TI  - Muscle overgrowth of the upper limb in a proximo-distal gradient and concurrent
      hypoplasia of the index finger.
AB  - BACKGROUND: There are many forms of congenital overgrowth of the upper limb. We
      aim to present the characteristics of a new form overgrowth of the upper limb.
      METHODS: This is a case series of 3 sporadic cases from 3 different Saudi Arabian
      families with progressive overgrowth of one or both upper limbs. The literature
      is reviewed for similar cases. RESULTS: The 3 cases were considered unique
      because they had almost identical clinical features as follows: the progressive
      overgrowth only affected the muscles (and not bones or other soft tissues); the
      palm was wide with abnormal dermatoglyphics; the space between the second and
      third metacarpals was wide resulting in radial deviation of the index finger
      metacarpal, the index finger was mildly hypoplastic, and the metacarpophalangeal
      joint of the thumb had a hyperextension deformity. Ulnar deviation of the fingers
      was not a constant feature. When the literature was reviewed, similar cases were
      found, but they were mostly discussed as an unusual form of windblown hand
      deformity because of the ulnar deviation of the fingers. CONCLUSION: The author
      believes that these cases present a new clinical form of overgrowth of the upper
      limb. LEVEL OF EVIDENCE: Level IV (case series).

PMID- 24686296
TI  - The Andean adaptive toolkit to counteract high altitude maladaptation: genome
      wide and phenotypic analysis of the Collas.
AB  - During their migrations out of Africa, humans successfully colonised and adapted
      to a wide range of habitats, including extreme high altitude environments, where
      reduced atmospheric oxygen (hypoxia) imposes a number of physiological
      challenges. This study evaluates genetic and phenotypic variation in the Colla
      population living in the Argentinean Andes above 3500 m and compares it to the
      nearby lowland Wichi group in an attempt to pinpoint evolutionary mechanisms
      underlying adaptation to high altitude hypoxia. We genotyped 730,525 SNPs in 25
      individuals from each population. In genome-wide scans of extended haplotype
      homozygosity Collas showed the strongest signal around VEGFB, which plays an
      essential role in the ischemic heart, and ELTD1, another gene crucial for heart
      development and prevention of cardiac hypertrophy. Moreover, pathway enrichment
      analysis showed an overrepresentation of pathways associated with cardiac
      morphology. Taken together, these findings suggest that Colla highlanders may
      have evolved a toolkit of adaptative mechanisms resulting in cardiac
      reinforcement, most likely to counteract the adverse effects of the permanently
      increased haematocrit and associated shear forces that characterise the Andean
      response to hypoxia. Regulation of cerebral vascular flow also appears to be part
      of the adaptive response in Collas. These findings are not only relevant to
      understand the evolution of hypoxia protection in high altitude populations but
      may also suggest new avenues for medical research into conditions where hypoxia
      constitutes a detrimental factor. 

PMID- 24686299
TI  - Fractures from trampolines: results from a national database, 2002 to 2011.
AB  - BACKGROUND: No study specifically analyzes trampoline fracture patterns across a
      large population. The purpose of this study was to determine such patterns.
      METHODS: We queried the National Electronic Injury Surveillance System database
      for trampoline injuries between 2002 and 2011, and the patients were analyzed by
      age, sex, race, anatomic location of the injury, geographical location of the
      injury, and disposition from the emergency department (ED). Statistical analyses
      were performed with SUDAAN 10 software. Estimated expenses were determined using
      2010 data. RESULTS: There were an estimated 1,002,735 ED visits for trampoline
      related injuries; 288,876 (29.0%) sustained fractures. The average age for those
      with fractures was 9.5 years; 92.7% were aged 16 years or younger; 51.7% were
      male, 95.1% occurred at home, and 9.9% were admitted. The fractures were located
      in the upper extremity (59.9%), lower extremity (35.7%), and axial skeleton
      (spine, skull/face, rib/sternum) (4.4%-spine 1.0%, skull/face 2.9%, rib/sternum
      0.5%). Those in the axial skeleton were older (16.5 y) than the upper extremity
      (8.7 y) or lower extremity (10.0 y) (P<0.0001) and more frequently male (67.9%).
      Lower extremity fractures were more frequently female (54.0%) (P<0.0001). The
      forearm (37%) and elbow (19%) were most common in the upper extremity; elbow
      fractures were most frequently admitted (20.0%). The tibia/fibula (39.5%) and
      ankle (31.5%) were most common in the lower extremity; femur fractures were most
      frequently admitted (57.9%). Cervical (36.4%) and lumbar (24.7%) were most common
      locations in the spine; cervical fractures were the most frequently admitted
      (75.6%). The total ED expense for all trampoline injuries over this 10-year
      period was $1.002 billion and $408 million for fractures. CONCLUSIONS: Trampoline
      fractures most frequently involve the upper extremity followed by the lower
      extremity, >90% occur in children. The financial burden to society is large.
      Further efforts for prevention are needed.

PMID- 24686300
TI  - Normal values of bony, cartilaginous, and labral coverage of the infant hip in MR
      imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is becoming more popular in the
      evaluation of residual hip dysplasia. Normal values of the bony, cartilaginous,
      and labral coverage in MRI are not published. The aim of our study was to
      establish reference values for normal hips at different ages and to assess the
      interobserver variability of such measurements. METHODS: MRIs of 115 normal hips
      in 73 children were analyzed. The bony, cartilaginous, and labral acetabular
      index (AI bone/cartilage/labrum) was measured in the coronal plane just posterior
      to the inferior branch of the triradiate cartilage. To determine interobserver
      variability, measurements were made by 3 different observers. Percentile graphs
      were established from the Student t distribution of the measurements grouped by 2
      years of age. RESULTS: Global interobserver variability for the measurement of
      the AI bone was excellent [intraclass correlation coefficient (ICC)=0.88]. For
      the AI cartilage and labrum the ICC was somewhat lower (ICC 0.78) but still rated
      as good. Age-dependent percentile graphs of the AI bone, cartilage, and labrum
      are presented. Although the AI bone decreased during childhood, the AI cartilage
      as well as the AI labrum stays relatively constant with the 50 percentile around
      5 degrees for the AI cartilage and -5 degrees for the AI labrum. The 90
      percentile is around 10 degrees for the AI cartilage and 0 degrees for the AI
      labrum. CONCLUSIONS: We present percentile graphs of age-related normal values.
      Although bony coverage increases during childhood, cartilaginous and labral
      coverage stay constant. We think that measuring an AI cartilage above 10 degrees
      or an AI cartilage above 0 degrees might be a good additional parameter to
      classify hips into the group of residual dysplasia. CLINICAL RELEVANCE: The
      knowledge of normal values for cartilaginous and labral coverage is a valuable
      adjunct in decision-making for secondary surgery in residual dysplasia. This was
      a retrospective cross-sectional study.

PMID- 24686302
TI  - Bio-Inspired glucose control in diabetes based on an analogue implementation of a
      beta-cell model.
AB  - This paper presents a bio-inspired method for in-vivo control of blood glucose
      based on a model of the pancreatic beta-cell. The proposed model is shown to be
      implementable using low-power analogue integrated circuits in CMOS, realizing a
      biologically faithful implementation which captures all the behaviours seen in
      physiology. This is then shown to be capable of glucose control using an in
      silico population of diabetic subjects achieving 93% of the time in tight
      glycemic target (i.e., [70, 140] mg/dl) . The proposed controller is then
      compared with a commonly used external physiological insulin delivery (ePID)
      controller for glucose control. Results confirm equivalent, or superior,
      performance in comparison with ePID. The system has been designed in a
      commercially available 0.35 MUm CMOS process and achieves an overall power
      consumption of 1.907 mW. 

PMID- 24686301
TI  - The role of capital realignment versus in situ stabilization for the treatment of
      slipped capital femoral epiphysis.
AB  - INTRODUCTION: Slipped capital femoral epiphysis (SCFE) can be treated by a
      variety of methods with the traditional method of in situ pin fixation being most
      commonly used. More recently, the Modified Dunn (Mod. Dunn) procedure consisting
      of capital realignment has been popularized as a treatment method for SCFE,
      particularly for more severe cases. Over the last 5 years, our institution has
      selectively used this method for more complex cases. The purpose of this article
      is to evaluate the differences between these 2 treatment methods in terms of
      avascular necrosis (AVN) rate, reoperation rate, and complication rate. METHODS:
      Eighty-eight hips that were surgically treated for SCFE between July 2004 and
      June 2012 met our inclusion criteria. The in situ fixation group included 71
      hips, whereas 17 hips were anatomically reduced with the Mod. Dunn procedure.
      Loder classification, severity, acuity, complication rate, and reoperation rate
      were determined for the 2 cohorts. The chi analysis was performed to evaluate the
      relationship between the treatment method and outcome. RESULTS: As expected,
      stable slips did well with in situ pinning with no cases of AVN, even in more
      severe slips. Ten stable slips were treated with the Mod. Dunn approach and 2
      (20%) developed AVN. Unstable slips were more difficult to treat with 3 of the 7
      hips stabilized in situ developing AVN (43%). Two of the 7 unstable slips treated
      by the Mod. Dunn procedure developed AVN (29%). The other outcomes studied
      (reoperation rate and complication rate) were not significantly related to the
      surgical treatment method (P = 0.732 and 0.261, respectively). CONCLUSIONS: In
      situ pinning remains a safe and predictable method for treatment of stable SCFE
      with no AVN noted, even in severe slips. Attempts to anatomically reduce stable
      slips led to severe AVN in 20% of cases, thus this treatment approach should be
      considered with caution. Treatment of unstable slips remains problematic with
      high AVN rates noted whether treated by in situ fixation or capital realignment
      (Mod. Dunn). LEVEL OF EVIDENCE: Level III retrospective comparative study.

PMID- 24686303
TI  - Reversible symptoms and clearance of mutant prion protein in an inducible model
      of a genetic prion disease in Drosophila melanogaster.
AB  - Prion diseases are progressive disorders that affect the central nervous system
      leading to memory loss, personality changes, ataxia and neurodegeneration. In
      humans, these disorders include Creutzfeldt-Jakob disease, kuru and Gerstmann
      Straussler-Scheinker (GSS) syndrome, the latter being a dominantly inherited
      prion disease associated with missense mutations in the gene that codes for the
      prion protein. The exact mechanism by which mutant prion proteins affect the
      central nervous system and cause neurological disease is not well understood. We
      have generated an inducible model of GSS disease in Drosophila melanogaster by
      temporally expressing a misfolded form of the murine prion protein in cholinergic
      neurons. Flies accumulating this mutant protein develop motor abnormalities which
      are associated with electrophysiological defects in cholinergic neurons. We find
      that, upon blocking the expression of the mutant protein, both behavioral and
      electrophysiological defects can be reversed. This represents the first case of
      reversibility reported in a model of genetic prion disease. Additionally, we
      observe that endogenous mechanisms exist within Drosophila that are capable of
      clearing the accumulated prion protein.

PMID- 24686306
TI  - Adaptive routing for dynamic on-body wireless sensor networks.
AB  - Energy is scarce in mobile computing devices including wearable and implantable
      devices in a wireless body area network. In this paper, an adaptive routing
      protocol is developed and analyzed which minimizes the energy cost per bit of
      information by using the channel information to choose the best strategy to route
      data. In this approach, the source node will switch between direct and relayed
      communication based on the quality of the link and will use the relay only if the
      channel quality is below a certain threshold. The mathematical model is then
      validated through simulations which shows that the adaptive routing strategy can
      improve energy efficiency significantly compared with existing methods. 

PMID- 24686305
TI  - Dynamics of interictal spikes and high-frequency oscillations during
      epileptogenesis in temporal lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE) is characterized in humans and in animal
      models by a seizure-free latent phase that follows an initial brain insult; this
      period is presumably associated to plastic changes in temporal lobe excitability
      and connectivity. Here, we analyzed the occurrence of interictal spikes and high
      frequency oscillations (HFOs; ripples: 80-200Hz and fast ripples: 250-500Hz) from
      48h before to 96h after the first seizure in the rat pilocarpine model of MTLE.
      Interictal spikes recorded with depth EEG electrodes from the hippocampus CA3
      area and entorhinal cortex (EC) were classified as type 1 (characterized by a
      spike followed by a wave) or type 2 (characterized by a spike with no wave). We
      found that: (i) there was a switch in the distribution of both types of
      interictal spikes before and after the occurrence of the first seizure; during
      the latent phase both types of interictal spikes predominated in the EC whereas
      during the chronic phase both types of spikes predominated in CA3; (ii) type 2
      spike duration decreased in both regions from the latent to the chronic phase;
      (iii) type 2 spikes associated to fast ripples occurred at higher rates in EC
      compared to CA3 during the latent phase while they occurred at similar rates in
      both regions in the chronic phase; and (iv) rates of fast ripples outside of
      spikes were higher in EC compared to CA3 during the latent phase. Our findings
      demonstrate that the transition from the latent to the chronic phase is
      paralleled by dynamic changes in interictal spike and HFO expression in EC and
      CA3. We propose that these changes may represent biomarkers of epileptogenicity
      in MTLE.

PMID- 24686304
TI  - High fat diet produces brain insulin resistance, synaptodendritic abnormalities
      and altered behavior in mice.
AB  - Insulin resistance and other features of the metabolic syndrome are increasingly
      recognized for their effects on cognitive health. To ascertain mechanisms by
      which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days
      or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined
      changes in brain insulin signaling responses, hippocampal synaptodendritic
      protein expression, and spatial working memory. Compared to normal control diet
      mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by
      failed activation of Akt, S6 and GSK3beta with ex-vivo insulin stimulation.
      Importantly, we found that expression of brain IPMK, which is necessary for
      mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD
      mouse hippocampus exhibited increased expression of serine-phosphorylated insulin
      receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as
      decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic
      densities, and synaptopodin, an actin-associated protein enriched in spine
      apparatuses. Spatial working memory was impaired as assessed by decreased
      spontaneous alternation in a T-maze. These findings indicate that HFD is
      associated with telencephalic insulin resistance and deleterious effects on
      synaptic integrity and cognitive behaviors.

PMID- 24686307
TI  - Priority-based time-slot allocation in wireless body area networks during medical
      emergency situations: an evolutionary game-theoretic perspective.
AB  - In critical medical emergency situations, wireless body area network (WBAN)
      equipped health monitoring systems treat data packets with critical information
      regarding patients' health in the same way as data packets bearing regular
      healthcare information. This snag results in a higher average waiting time for
      the local data processing units (LDPUs) transmitting data packets of higher
      importance. In this paper, we formulate an algorithm for Priority-based
      Allocation of Time Slots (PATS) that considers a fitness parameter characterizing
      the criticality of health data that a packet carries, energy consumption rate for
      a transmitting LDPU, and other crucial LDPU properties. Based on this fitness
      parameter, we design the constant model hawk-dove game that ensures prioritizing
      the LDPUs based on crucial properties. In comparison with the existing works on
      priority-based wireless transmission, we measure and take into consideration the
      urgency, seriousness, and criticality associated with an LDPU and, thus, allocate
      transmission time slots proportionately. We show that the number of transmitting
      LDPUs in medical emergency situations can be reduced by 25.97%, in comparison
      with the existing time-division-based techniques. 

PMID- 24686309
TI  - Treatment of oral fungal infections using antimicrobial photodynamic therapy: a
      systematic review of currently available evidence.
AB  - The aim was to review the efficacy of antimicrobial photodynamic therapy (PDT) in
      the treatment of oral fungal infections. To address the focused question "Should
      PDT be considered a possible treatment regimen for oral fungal infections?"
      PubMed/Medline and Google-Scholar databases were searched from 1997 up to March
      2014 using various combinations of the following key words: "Candida albicans";
      "Candidiasis"; "Candidosis"; "denture stomatitis"; "oral" and "photodynamic
      therapy". Original studies, experimental studies and articles published solely in
      English language were sought. Letters to the editor, historic reviews and
      unpublished data were excluded. Pattern of the present literature review was
      customized to mainly summarize the pertinent information. Fifteen studies (3
      clinical and 12 experimental) were included. All studies reported antimicrobial
      PDT to be an effective antifungal treatment strategy. One study reported PDT and
      azole therapy to be equally effective in the treatment of oral fungal infections.
      Methylene blue, toluidine blue and porphyrin derivative were the most commonly
      used photosensitizers. The laser wavelengths and power output ranged between ~455
      nm-660 nm and 30 mW-400 mW. The energy fluence ranged between 26-245 J cm(-2) and
      the duration or irradiation ranged between 10 seconds and 26 minutes. Clinical
      effectiveness of antimicrobial PDT as a potent therapeutic strategy for oral
      fungal infections requires further investigations. 

PMID- 24686308
TI  - The hallmarks of fibroblast ageing.
AB  - Ageing is influenced by the intrinsic disposition delineating what is maximally
      possible and extrinsic factors determining how that frame is individually
      exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post
      mitotic skin compartment mainly consisting of extracellular matrix and
      fibroblasts. Dermal fibroblasts are long-lived cells constantly undergoing damage
      accumulation and (mal-)adaptation, thus constituting a powerful indicator system
      for human ageing. Here, we use the systematic of ubiquitous hallmarks of ageing
      (Lopez-Otin et al., 2013, Cell 153) to categorise the available knowledge
      regarding dermal fibroblast ageing. We discriminate processes inducible in
      culture from phenomena apparent in skin biopsies or primary cells from old
      donors, coming to the following conclusions: (i) Fibroblasts aged in culture
      exhibit most of the established, ubiquitous hallmarks of ageing. (ii) Not all of
      these hallmarks have been detected or investigated in fibroblasts aged in situ
      (in the skin). (iii) Dermal fibroblasts aged in vitro and in vivo exhibit
      additional features currently not considered ubiquitous hallmarks of ageing. (iv)
      The ageing process of dermal fibroblasts in their physiological tissue
      environment has only been partially elucidated, although these cells have been a
      preferred model of cell ageing in vitro for decades. 

PMID- 24686310
TI  - Hybrid metaheuristic approaches to the expectation maximization for estimation of
      the hidden Markov model for signal modeling.
AB  - The expectation maximization (EM) is the standard training algorithm for hidden
      Markov model (HMM). However, EM faces a local convergence problem in HMM
      estimation. This paper attempts to overcome this problem of EM and proposes
      hybrid metaheuristic approaches to EM for HMM. In our earlier research, a hybrid
      of a constraint-based evolutionary learning approach to EM (CEL-EM) improved HMM
      estimation. In this paper, we propose a hybrid simulated annealing stochastic
      version of EM (SASEM) that combines simulated annealing (SA) with EM. The novelty
      of our approach is that we develop a mathematical reformulation of HMM estimation
      by introducing a stochastic step between the EM steps and combine SA with EM to
      provide better control over the acceptance of stochastic and EM steps for better
      HMM estimation. We also extend our earlier work and propose a second hybrid which
      is a combination of an EA and the proposed SASEM, (EA-SASEM). The proposed EA
      SASEM uses the best constraint-based EA strategies from CEL-EM and stochastic
      reformulation of HMM. The complementary properties of EA and SA and stochastic
      reformulation of HMM of SASEM provide EA-SASEM with sufficient potential to find
      better estimation for HMM. To the best of our knowledge, this type of
      hybridization and mathematical reformulation have not been explored in the
      context of EM and HMM training. The proposed approaches have been evaluated
      through comprehensive experiments to justify their effectiveness in signal
      modeling using the speech corpus: TIMIT. Experimental results show that proposed
      approaches obtain higher recognition accuracies than the EM algorithm and CEL-EM
      as well.

PMID- 24686311
TI  - Reliable filtering with strict dissipativity for T-S fuzzy time-delay systems.
AB  - In this paper, the problem of reliable filter design with strict dissipativity
      has been investigated for a class of discrete-time T-S fuzzy time-delay systems.
      Our attention is focused on the design of a reliable filter to ensure a strictly
      dissipative performance for the filtering error system. Based on the reciprocally
      convex approach, firstly, a sufficient condition of reliable dissipativity
      analysis is proposed for T-S fuzzy systems with time-varying delays and sensor
      failures. Then, a reliable filter with strict dissipativity is designed by
      solving a convex optimization problem, which can be efficiently solved by
      standard numerical algorithms. Finally, numerical examples are provided to
      illustrate the effectiveness of the developed techniques. 

PMID- 24686312
TI  - Tolerance approach to possibilistic nonlinear regression with interval data.
AB  - We study possibilistic nonlinear regression models with crisp and/or interval
      data. Herein, the task is to compute tight interval regression parameters such
      that all observed output data (either crisp or interval) are covered by the range
      of the nonlinear interval regression function. We propose a method for
      determination of interval regression parameters based on the tolerance approach
      developed by the authors for the linear case. We define two classes of nonlinear
      regression models for which efficient algorithms exist. For other models, we
      provide some extensions allowing to calculate lower and upper bounds on the
      widths of the optimal interval regression parameters. We also discuss other
      approaches to interval regression than the possibilistic one. We illustrate the
      theory by examples. 

PMID- 24686313
TI  - Recovering chaotic properties from small data.
AB  - Physical properties are obviously essential to study a chaotic system that
      generates discrete-time signals, but recovering chaotic properties of a signal
      source from small data is a very troublesome work. Existing chaotic models are
      weak in dealing with such case in that most of them need big data to exploit
      those properties. In this paper, geometric theory is considered to solve this
      problem. We build a smooth trajectory from series to implicitly exhibit the
      chaotic properties with series-nonuniform rational B-spline (S-NURBS) modeling
      method, which is presented by our team to model slow-changing chaotic time
      series. As for the part of validation, we reveal how well our model recovers the
      properties from both the statistical and the chaotic aspects to confirm the
      effectiveness of the model. Finally a practical chaotic model is built up to
      recover the chaotic properties contained in the Musa standard dataset, which is
      used in analyzing software reliability, thereby further proves the high
      credibility of this model in practical time series. The effectiveness of the S
      NURBS modeling leads us to believe that it is really a feasible and worthy
      research area to study chaotic systems from geometric perspective. For this
      reason, we reckon that we have opened up a new horizon for chaotic system
      research. 

PMID- 24686314
TI  - Photoresist-free fully self-patterned transparent amorphous oxide thin-film
      transistors obtained by sol-gel process.
AB  - We demonstrated self-patterned solution-processed amorphous oxide semiconductor
      thin-film transistors (TFTs) using photosensitive sol-gels. The photosensitive
      sol-gels were synthesized by adding beta-diketone compounds, i.e., benzoylacetone
      and acetylacetone, to sol-gels. The chemically modified photosensitive sol-gels
      showed a high optical absorption at specific wavelengths due to the formation of
      metal chelate bonds. Photoreactions of the modified solutions enabled a
      photoresist-free process. Moreover, Zn-Sn-O with a high Sn ratio, which is hard
      to wet-etch using conventional photolithography due to its chemical durability,
      was easily patterned via the self-patterning process. Finally, we fabricated a
      solution-processed oxide TFT that included fully self-patterned electrodes and an
      active layer. 

PMID- 24686315
TI  - Do genetic mutations and genotypes contribute to onychomycosis?
AB  - BACKGROUND: The variability in susceptibility to onychomycosis for individuals
      exposed to the same environmental risk factors raises the possibility that there
      may be individuals with a genetic predisposition to dermatophyte infection.
      OBJECTIVE: To determine whether there are genetic mutations or genotypes which
      contribute to onychomycosis. METHODS: The PubMed database was searched for
      examples of immune deficiencies resulting in dermatophyte infections. RESULTS:
      There are mutations in the innate immune receptors Dectin-1 and its adaptor
      protein CARD9 which result in familial mucocutaneous infections. There are also
      specific human leukocyte antigen genotypes that are more common in individuals
      and families with a high prevalence of onychomycosis. In addition, some patients
      have been reported with insufficient levels of CD4+CD25+ regulatory T cells.
      These deficits impair a full innate and adaptive immune response and may result
      in chronic or recurrent infections. CONCLUSIONS: There are documented mutations
      and genotypes that contribute to familial and individual susceptibility to
      onychomycosis.

PMID- 24686317
TI  - Timing of inorganic phosphate release modulates the catalytic activity of ATP
      driven rotary motor protein.
AB  - F1-ATPase is a rotary motor protein driven by ATP hydrolysis. The rotary motion
      of F1-ATPase is tightly coupled to catalysis, in which the catalytic sites
      strictly obey the reaction sequences at the resolution of elementary reaction
      steps. This fine coordination of the reaction scheme is thought to be important
      to achieve extremely high chemomechanical coupling efficiency and reversibility,
      which is the prominent feature of F1-ATPase among molecular motor proteins. In
      this study, we intentionally change the reaction scheme by using single-molecule
      manipulation, and we examine the resulting effect on the rotary motion of F1
      ATPase. When the sequence of the products released, that is, ADP and inorganic
      phosphate, is switched, we find that F1 frequently stops rotating for a long
      time, which corresponds to inactivation of catalysis. This inactive state
      presents MgADP inhibition, and thus, we find that an improper reaction sequence
      of F1-ATPase catalysis induces MgADP inhibition. 

PMID- 24686318
TI  - Hypothermia makes cerebral resistance index a poor prognostic tool in
      encephalopathic newborns.
AB  - BACKGROUND: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may
      cause death or life-long disability. Acute encephalopathy may also affect
      cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) <=0.55
      was predictive of poor outcome in normothermic NE infants. Recent studies have
      questioned its predictive power during therapeutic hypothermia (HT). OBJECTIVE:
      To assess the predictive power of RI during HT and after rewarming. METHODS: 45
      infants with NE treated with HT for 72 h had their RI calculated during early
      (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h).
      Poor outcome was defined as death or abnormalities on day 10 magnetic resonance
      imaging shown to predict severe neuromotor disability. RESULTS: RI <=0.55 during
      cooling did not differentiate between good and poor outcome (late cooling, p =
      0.08), but was powerful after rewarming (p = 0.004). RI <=0.55 predicted true
      poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling
      and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in
      86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after
      rewarming. CONCLUSIONS: Low RI is not predictive of poor outcome during HT in NE
      infants, but regains the predictive power seen in normothermic infants after
      rewarming.

PMID- 24686316
TI  - eIF5B employs a novel domain release mechanism to catalyze ribosomal subunit
      joining.
AB  - eIF5B is a eukaryal translational GTPase that catalyzes ribosomal subunit joining
      to form elongation-competent ribosomes. Despite its central role in protein
      synthesis, the mechanistic details that govern the function of eIF5B or its
      archaeal and bacterial (IF2) orthologs remained unclear. Here, we present six
      high-resolution crystal structures of eIF5B in its apo, GDP- and GTP-bound form
      that, together with an analysis of the thermodynamics of nucleotide binding,
      provide a detailed picture of the entire nucleotide cycle performed by eIF5B. Our
      data show that GTP binding induces significant conformational changes in the two
      conserved switch regions of the G domain, resulting in the reorganization of the
      GTPase center. These rearrangements are accompanied by the rotation of domain II
      relative to the G domain and release of domain III from its stable contacts with
      switch 2, causing an increased intrinsic flexibility in the free GTP-bound eIF5B.
      Based on these data, we propose a novel domain release mechanism for eIF5B/IF2
      activation that explains how eIF5B and IF2 fulfill their catalytic role during
      ribosomal subunit joining.

PMID- 24686319
TI  - A high throughput MHC II binding assay for quantitative analysis of peptide
      epitopes.
AB  - Biochemical assays with recombinant human MHC II molecules can provide rapid,
      quantitative insights into immunogenic epitope identification, deletion, or
      design(1,2). Here, a peptide-MHC II binding assay is scaled to 384-well format.
      The scaled down protocol reduces reagent costs by 75% and is higher throughput
      than previously described 96-well protocols(1,3-5). Specifically, the
      experimental design permits robust and reproducible analysis of up to 15 peptides
      against one MHC II allele per 384-well ELISA plate. Using a single liquid
      handling robot, this method allows one researcher to analyze approximately ninety
      test peptides in triplicate over a range of eight concentrations and four MHC II
      allele types in less than 48 hr. Others working in the fields of protein
      deimmunization or vaccine design and development may find the protocol to be
      useful in facilitating their own work. In particular, the step-by-step
      instructions and the visual format of JoVE should allow other users to quickly
      and easily establish this methodology in their own labs. 

PMID- 24686320
TI  - Anesthesia and ventilation strategies in children with asthma: part II -
      intraoperative management.
AB  - PURPOSE OF REVIEW: As asthma is a frequent disease especially in children,
      anesthetists are increasingly providing anesthesia for children requiring
      elective surgery with well controlled asthma but also for those requiring urgent
      surgery with poorly controlled or undiagnosed asthma. This second part of this
      two-part review details the medical and ventilatory management throughout the
      perioperative period in general but also includes the perioperative management of
      acute bronchospasm and asthma exacerbations in children with asthma. RECENT
      FINDINGS: Multiple observational trials assessing perioperative respiratory
      adverse events in healthy and asthmatic children provide the basis for
      identifying risk reduction strategies. Mainly, animal experiments and to a small
      extent clinical data have advanced our understanding of how anesthetic agents
      effect bronchial smooth muscle tone and blunt reflex bronchoconstriction. Asthma
      treatment outside anesthesia is well founded on a large body of
      evidence.Perioperative prevention strategies have increasingly been studied.
      However, evidence on the perioperative management, including mechanical
      ventilation strategies of asthmatic children, is still only fair, and further
      research is required. SUMMARY: To minimize the considerable risk of perioperative
      respiratory adverse events in asthmatic children, perioperative management should
      be based on two main pillars: the preoperative optimization of asthma treatment
      (please refer to the first part of this two-part review) and - the focus of this
      second part of this review - the optimization of anesthesia management in order
      to optimize lung function and minimize bronchial hyperreactivity in the
      perioperative period.

PMID- 24686321
TI  - Reprogramming cancer cells to pluripotency: an experimental tool for exploring
      cancer epigenetics.
AB  - The epigenetic marks displayed by a cancer cell originate from two separate
      processes: The most prominent epigenetic signatures are associated with the cell
      of origin, i.e., the lineage and cell type identity imposed during development.
      The second set comprises those aberrant cancer-specific epigenetic marks that
      appear during tumor initiation or subsequent malignant progression. These are
      generally thought to associate with tumor-promoting pathways. As biochemical
      pathways regulating epigenetic mechanisms are potentially "druggable" and
      reversible, there is considerable interest in defining their roles in tumor
      genesis and growth, as they may represent therapeutic targets for treatment of
      human neoplasias. (1) However, despite the potential importance of epigenetic
      modifications in human cancer, it has been difficult to determine when, where and
      how epigenetic disruptions occur, and if they have important functional roles in
      sustaining the malignant state. 

PMID- 24686323
TI  - Joseph Lister and the performance of antiseptic surgery.
AB  - This article highlights a neglected feature of Joseph Lister's work, namely how,
      in addition to promoting germ theories and the principles of the antiseptic
      system, he also devoted much time and effort to communicating the performative
      aspects of antisepsis and of the many other surgical innovations that he
      developed. Attention to 'detail' and striving for 'improvement' were crucial to
      Listerian practice, and he sought to convey his credo in three main ways: first,
      his publications aimed at 'bringing the subject out in the same sort of way as it
      had been worked out by himself'; second, he set out strict protocols and
      information on materials and methods, yet also encouraged surgeons to improvise;
      and third, he made himself an exemplar of a new form of professionalism, which
      made constancy and vigilance in practice a moral duty for surgeons.

PMID- 24686322
TI  - Extreme deep white matter hyperintensity volumes are associated with African
      American race.
AB  - BACKGROUND: African Americans (AAs) have a higher prevalence of extreme ischemic
      white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) than do
      European Americans (EAs) based on the Cardiovascular Health Study (CHS) score.
      Ischemic white matter disease, limited to the deep white matter, may be
      biologically distinct from disease in other regions and may reflect a previously
      observed trend toward an increased risk of subcortical lacunar infarcts in AAs.
      We hypothesized that extreme deep WMH volume (DWMV) or periventricular volume
      (PV) may also have a higher prevalence in AAs. Thus, we studied extreme CHS
      scores and extreme DWMV and PV in a healthy population enriched for
      cardiovascular disease risk factors. METHODS: We imaged the brains of 593
      subjects who were first-degree relatives of probands with early onset coronary
      disease prior to 60 years of age. WMHs were manually delineated on 3-tesla
      cranial MRI by a trained radiology reader; the location and volume of lesions
      were characterized using automated software. DWMV and PV were measured directly
      with automated software, and the CHS score was determined by a neuroradiologist.
      Volumes were characterized as being in the upper 25% versus lower 75% of total
      lesion volume. Volumes in the upper versus the remaining quartiles were examined
      for AA versus EA race using multiple logistic regression (generalized estimating
      equations adjusted for family relatedness) and adjusted for major vascular
      disease risk factors including age >=55 years versus <55, sex, current smoking,
      obesity, hypertension, diabetes and low-density lipoprotein >160 mg/dl. RESULTS:
      Participants were 58% women and 37% AAs, with a mean age of 51.5 +/- 11.0 years
      (range, 29-74 years). AAs had significantly higher odds of having extreme DWMVs
      (odds ratio, OR, 1.8; 95% confidence interval, CI, 1.2-2.9; p = 0.0076)
      independently of age, sex, hypertension and all other risk factors. AAs also had
      significantly higher odds of having extreme CHS scores >=3 (OR, 1.3; 95% CI, 1.1
      3.6; p = 0.025). Extreme PV was not significantly associated with AA race (OR,
      1.3; 95% CI, 0.81-2.1; p = 0.26). CONCLUSIONS: AAs from families with early-onset
      cardiovascular disease are more likely to have extreme DWMVs (a subclinical form
      of cerebrovascular disease) and an extreme CHS score, but not extreme PV,
      independently of age and other cardiovascular disease risk factors. These
      findings suggest that this AA population is at an increased risk for DWMV and may
      be at an increased risk for future subcortical stroke. Longitudinal studies are
      required to see if DWMV is predictive of symptomatic subcortical strokes in this
      population.

PMID- 24686325
TI  - Comment on: Valette et al. Melanocortin-4 receptor mutations and polymorphisms do
      not affect weight loss after bariatric surgery. PLOS ONE 2012; 7(11):E48221.

PMID- 24686324
TI  - A comparison of the effects of epidural analgesia versus traditional pain
      management on outcomes after gastric cancer resection: a population-based study.
AB  - BACKGROUND AND OBJECTIVES: Epidural analgesia may increase survival after cancer
      surgery by reducing recurrence. This population-based study compared survival and
      treated recurrence after gastric cancer resection between patients receiving
      epidurals and those who did not. METHODS: We used the linked federal
      Surveillance, Epidemiology, and End Results Program/Medicare database to identify
      patients aged 66 years or older with nonmetastatic gastric carcinoma diagnosed
      1996 to 2005 who underwent resection. Exclusions included diagnosis at autopsy,
      no Medicare Part B, familial cancer syndrome, emergency surgery, and laparoscopic
      procedures. Epidurals were identified by Current Procedural Terminology codes.
      Treated recurrence was defined as chemotherapy greater than or equal to 16 months
      and/or radiation greater than or equal to 12 months after surgery. Recurrence was
      compared by conditional logistic regression. Survival was compared via marginal
      Cox proportional hazards regression model. RESULTS: We identified 2745 patients,
      766 of whom had epidural codes. Patients receiving epidurals were more likely to
      have regional disease, be white, and live in areas with relatively high
      socioeconomic status. Overall treated recurrence was 25.6% (27.5% epidural and
      24.9% nonepidural). In the adjusted logistic regression, there was no difference
      in recurrence (odds ratio, 1.40; 95% confidence interval [CI], 0.96-2.05). Median
      survival did not differ: 28.1 months (95% CI, 24.8-32.3) in the epidural versus
      27.4 months (95% CI, 24.8-30.0) in the nonepidural groups. The marginal Cox
      models showed no association between epidural use and mortality (adjusted hazard
      ratio, 0.93; 95% CI, 0.84-1.03). CONCLUSIONS: There was no difference between
      groups regarding treated recurrence or survival. Whether this is true or simply a
      result of insufficient power is unclear. Prospective studies are needed to
      provide stronger evidence.

PMID- 24686326
TI  - Upconversion fluorescence resonance energy transfer biosensor for sensitive
      detection of human immunodeficiency virus antibodies in human serum.
AB  - A facile one-step approach was proposed to prepare hydrophilic and peptide
      functionalized upconversion nanoparticles (UCNPs), which were used in the design
      of a biosensor for the sensitive and selective determination of human
      immunodeficiency virus antibodies in human serum based on FRET from the UCNPs to
      the graphene oxide. 

PMID- 24686327
TI  - Long term chronic Pseudomonas aeruginosa airway infection in mice.
AB  - A mouse model of chronic airway infection is a key asset in cystic fibrosis (CF)
      research, although there are a number of concerns regarding the model itself.
      Early phases of inflammation and infection have been widely studied by using the
      Pseudomonas aeruginosa agar-beads mouse model, while only few reports have
      focused on the long-term chronic infection in vivo. The main challenge for long
      term chronic infection remains the low bacterial burden by P. aeruginosa and the
      low percentage of infected mice weeks after challenge, indicating that bacterial
      cells are progressively cleared by the host. This paper presents a method for
      obtaining efficient long-term chronic infection in mice. This method is based on
      the embedding of the P. aeruginosa clinical strains in the agar-beads in vitro,
      followed by intratracheal instillation in C57Bl/6NCrl mice. Bilateral lung
      infection is associated with several measurable read-outs including weight loss,
      mortality, chronic infection, and inflammatory response. The P. aeruginosa RP73
      clinical strain was preferred over the PAO1 reference laboratory strain since it
      resulted in a comparatively lower mortality, more severe lesions, and higher
      chronic infection. P. aeruginosa colonization may persist in the lung for over
      three months. Murine lung pathology resembles that of CF patients with advanced
      chronic pulmonary disease. This murine model most closely mimics the course of
      the human disease and can be used both for studies on the pathogenesis and for
      the evaluation of novel therapies. 

PMID- 24686328
TI  - Computational investigation of structural and electronic properties of aqueous
      interfaces of GaN, ZnO, and a GaN/ZnO alloy.
AB  - The GaN/ZnO alloy functions as a visible-light photocatalyst for splitting water
      into hydrogen and oxygen. As a first step toward understanding the mechanism and
      energetics of water-splitting reactions, we investigate the microscopic structure
      of the aqueous interfaces of the GaN/ZnO alloy and compare them with the aqueous
      interfaces of pure GaN and ZnO. Specifically, we have studied the (1010) surface
      of GaN and ZnO and the (1010) and (1210) surfaces of the 1 : 1 GaN/ZnO alloy. The
      calculations are carried out using first-principles density functional theory
      based molecular dynamics (DFT-MD). The structure of water within a 3 A distance
      from the semiconductor surface is significantly altered by the acid/base
      chemistry of the aqueous interface. Water adsorption on all surfaces is
      substantially dissociative such that the surface anions (N or O) act as bases
      accepting protons from dissociated water molecules while the corresponding
      hydroxide ions bond with surface cations (Ga or Zn). Additionally, the hard-wall
      interface presented by the semiconductor imparts ripples in the density of water.
      Beyond a 3 A distance from the semiconductor surface, water exhibits a bulk-like
      hydrogen bond network and oxygen-oxygen radial distribution function. Taken
      together, these characteristics represent the resting (or "dark") state of the
      catalytic interface. The electronic structure analysis of the aqueous GaN/ZnO
      interface suggests that the photogenerated holes may get trapped on interface
      species other than the adsorbed OH(-) ions. This suggests additional dynamical
      steps in the water oxidation process.

PMID- 24686329
TI  - Soft-solid deformation mechanics at the tip of an embedded needle.
AB  - Motivated by a recently developed technique for measuring soft materials
      properties at the tip of an embedded needle [Zimberlin, et al., Soft Matter,
      2007, 3, 763], the mechanics of elasticity- and surface tension-governed void
      growth within a neo-Hookean material is explored. Previous efforts to describe
      this technique relied on a hybrid spherical void/spherical cap approximation,
      thus assuming a spatially homogeneous deformation, i.e., no stress
      concentrations. We find that despite the inhomogeneities in needle-mediated
      growth, utilization of an areal surface stretch ratio as the deformation
      parameter yields good agreement between the spherical void and needle geometries.

PMID- 24686330
TI  - Slow modulations of high-frequency activity (40-140-Hz) discriminate preictal
      changes in human focal epilepsy.
AB  - Recent evidence suggests that some seizures are preceded by preictal changes that
      start from minutes to hours before an ictal event. Nevertheless an adequate
      statistical evaluation in a large database of continuous multiday recordings is
      still missing. Here, we investigated the existence of preictal changes in long
      term intracranial recordings from 53 patients with intractable partial epilepsy
      (in total 531 days and 558 clinical seizures). We describe a measure of brain
      excitability based on the slow modulation of high-frequency gamma activities (40
      140 Hz) in ensembles of intracranial contacts. In prospective tests, we found
      that this index identified preictal changes at levels above chance in 13.2% of
      the patients (7/53), suggesting that results may be significant for the whole
      group (p < 0.05). These results provide a demonstration that preictal states can
      be detected prospectively from EEG data. They advance understanding of the
      network dynamics leading to seizure and may help develop novel seizure prediction
      algorithms.

PMID- 24686332
TI  - Clinical application of the "pedicle exposure technique" for atlantoaxial
      instability patients with a narrow c1 posterior arch.
AB  - STUDY DESIGN: This was a retrospective study. OBJECTIVE: The aim of this study
      was to test a new surgical approach, that is, "pedicle exposure technique," for
      atlantoaxial instability (AAI) patients with C1 posterior arches measuring <4 mm,
      and to determine its feasibility and clinical outcomes. SUMMARY OF BACKGROUND
      DATA: C1 posterior arch screw placement is one of the most effective methods for
      AAI; however, several studies showed this method to be restricted when the
      posterior arch measures <4 mm. Hence, modification of this technique is necessary
      to expand its indications. PATIENTS AND METHODS: The average height of the C1
      posterior arch in 79 AAI cases was 3.3 (range, 2.5-3.9) mm. All patients were
      treated by the C1 "pedicle exposure technique" and C2 pedicle screw fixation. The
      feasibility and clinical outcome of this technique were analyzed by postoperative
      x-rays, computed tomography, and Visual Analogue Score and Japan Department of
      Orthopedics Association score. RESULTS: A total of 158 screws were successfully
      placed into the atlas in all 79 patients. There were no vertebral artery or
      spinal cord injuries. Venous plexus bleeding was encountered in 3 patients; there
      were no cases of new onset occipital neuralgia. Three screws penetrated into the
      external wall of the C1 lateral mass and 4 screws into the internal wall. Seventy
      nine patients were followed up for 6-80 months. Bony fusion was confirmed in all
      cases within 3-6 months by computed tomography; there were no instrument
      failures. Significant differences in preoperative and postoperative Visual
      Analogue Score and Japan Department of Orthopedics Association score were found.
      Thirty-six and 15 of 62 patients with preoperative neck pain had alleviation or
      resolution of symptoms, respectively; 33 of 36 patients with myelopathy
      demonstrated significant improvement. CONCLUSIONS: The "pedicle exposure
      technique" is an effective alternative in patients with the C1 posterior arch
      measuring <4 mm. In consideration of a high screw entry point on the C1 posterior
      arch, similar to the C1 posterior arch screw technique, we propose that this new
      technique can reduce venous plexus and C2 nerve root injury while providing
      effective biomechanical stability.

PMID- 24686334
TI  - Multilevel anterior cervical discectomy and fusion with plate fixation for
      juvenile unilateral muscular atrophy of the distal upper extremity accompanied by
      cervical kyphosis.
AB  - STUDY DESIGN: A retrospective clinical study was conducted and related
      literatures were reviewed. OBJECT: This study aimed to evaluate outcome of
      multilevel anterior cervical discectomy and fusion with plate fixation for
      juvenile unilateral muscular atrophy of the distal upper extremity accompanied by
      cervical kyphosis. SUMMARY OF BACKGROUND DATA: Juvenile unilateral muscular
      atrophy of the distal upper extremity is a rare disease. Traditional treatment
      uses a neck collar to immobilize neck motion. However, if the disease is
      accompanied by cervical kyphosis, conservative treatment is difficult to correct
      cervical kyphosis and the prognosis is worsened. Therefore, it is important to
      initially apply surgical treatment for juvenile unilateral muscular atrophy
      accompanied with cervical kyphosis. METHODS: From March 2008 to May 2010, 4
      patients were transferred to our spine medical center because of a history of
      slowly progressive distal weakness and atrophy of their hands and forearms. Four
      patients were diagnosed with Hirayama disease accompanied with cervical kyphosis
      based on their clinical representations and radiologic findings. After
      conservative treatment failed, these patients underwent multilevel anterior
      cervical discectomy and fusion with plate fixation. The clinical outcomes were
      retrospectively evaluated with follow-up ranging from 1.5 to 3 years. RESULTS:
      The clinical and radiologic follow-up indicated satisfactory clinical relief from
      symptoms, cervical sagittal alignment and cervical spinal canal volume, for all
      the patients. Within 6 months after surgery, the JOA score improved from a
      preoperative average of 14 to a postoperative average of 16.3; JOA recovery rates
      of all patients were more than good level. The muscle strengths of intrinsic
      muscles, wrist flexors and extensors, and biceps and triceps muscle improved on
      average by 1 grade. No complications occurred. CONCLUSIONS: Hirayama disease is a
      rare disease, a proper diagnosis of which can be made based on significant
      clinical symptoms and neurological imaging (dynamic MRI). The primary results
      from this study showed the tendency that multilevel anterior cervical discectomy
      and fusion with plate fixation is a preferred treatment for patients showing
      anterior effacement and apparent cervical kyphosis.

PMID- 24686335
TI  - Developmental and clinical overview of lithopaidion.
AB  - Lithopaidion, or stone child, is generally a single rare asymptomatic formation
      that evolves from an undiagnosed and untreated advanced abdominal pregnancy. The
      dead fetus is retained in the maternal abdominal cavity, which causes
      calcification. In this paper, we review the literature on the epidemiology,
      etiopathogenesis and clinical features of lithopaidion and report a unique case
      of lithokelyphos in a patient with an ectopic fallopian pregnancy. We propose a
      model to unify the data. The new word 'lithopaidion' can be utilized instead of
      lithopedion.

PMID- 24686336
TI  - Primary strategies for HPV infection and cervical cancer prevention.
AB  - Counseling messages for tobacco cessation, condom use, circumcision, and
      selective choice in the number of sexual partners can help reduce the risk of
      cervical cancer. Other sexual behavioral and reproductive risk factors for
      cervical cancer are a younger age at first intercourse and at first full-term
      pregnancy as well as increasing duration of combined hormonal oral contraceptive
      use. Micronutrients and supplements can reduce the risk of human papillomavirus
      infection, persistence, progression, and regression. Some human papillomavirus
      infections can be prevented by vaccination. Cervical cancer is best prevented by
      screening. 

PMID- 24686338
TI  - Inferring speaker attributes in adductor spasmodic dysphonia: ratings from
      unfamiliar listeners.
AB  - PURPOSE: To determine whether unfamiliar listeners' perceptions of speakers with
      adductor spasmodic dysphonia (ADSD) differ from control speakers on the
      parameters of relative age, confidence, tearfulness, and vocal effort and are
      related to speaker-rated vocal effort or voice-specific quality of life. METHOD:
      Twenty speakers with ADSD (including 6 speakers with ADSD plus tremor) and 20 age
      and sex-matched controls provided speech recordings, completed a voice-specific
      quality-of-life instrument (Voice Handicap Index; Jacobson et al., 1997), and
      rated their own vocal effort. Twenty listeners evaluated speech samples for
      relative age, confidence, tearfulness, and vocal effort using rating scales.
      RESULTS: Listeners judged speakers with ADSD as sounding significantly older,
      less confident, more tearful, and more effortful than control speakers (p < .01).
      Increased vocal effort was strongly associated with decreased speaker confidence
      (rs = .88-.89) and sounding more tearful (rs = .83-.85). Self-rated speaker
      effort was moderately related (rs = .45-.52) to listener impressions. Listeners'
      perceptions of confidence and tearfulness were also moderately associated with
      higher Voice Handicap Index scores (rs = .65-.70). CONCLUSION: Unfamiliar
      listeners judge speakers with ADSD more negatively than control speakers, with
      judgments extending beyond typical clinical measures. The results have
      implications for counseling and understanding the psychosocial effects of ADSD.

PMID- 24686337
TI  - BAX channel activity mediates lysosomal disruption linked to Parkinson disease.
AB  - Lysosomal disruption is increasingly regarded as a major pathogenic event in
      Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased
      levels of lysosomal-associated proteins and accumulation of undegraded
      autophagosomes (AP) are observed in PD-derived samples, including fibroblasts,
      induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain
      tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD
      related lysosomal breakdown to abnormal lysosomal membrane permeabilization
      (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent
      lysosomal defects remain virtually unknown, thereby precluding their potential
      therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2
      associated X protein), which permeabilizes mitochondrial membranes in PD models
      and is activated in PD patients, translocates and internalizes into lysosomal
      membranes early following treatment with the parkinsonian neurotoxin MPTP, both
      in vitro and in vivo, within a time-frame correlating with LMP, lysosomal
      disruption, and autophagosome accumulation and preceding mitochondrial
      permeabilization and dopaminergic neurodegeneration. Supporting a direct
      permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to
      induce LMP in purified mouse brain lysosomes and the latter can be prevented by
      pharmacological blockade of BAX channel activity. Furthermore, pharmacological
      BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse
      AP accumulation, and attenuate mitochondrial permeabilization and overall
      nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall,
      our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP,
      and point to small molecules able to block BAX channel activity as potentially
      beneficial to attenuate both lysosomal defects and neurodegeneration occurring in
      PD.

PMID- 24686339
TI  - Metallodendrimers in three oxidation states with electronically interacting
      metals and stabilization of size-selected gold nanoparticles.
AB  - Metallodendrimers containing redox-robust centres may have applications in
      molecular redox recognition, sensing, biosensing and catalysis. So far, however,
      no metallodendrimer is known in several oxidation states. Here we report
      metallodendrimers with two electronically communicating iron centres that are
      stable and isolated in both the Fe(II) and Fe(III) oxidation states, and in
      addition as class-II mixed-valent Fe(II)Fe(III) complexes. These dendrons are
      branched to arene-centred dendrimer cores either by Sonogashira coupling or
      'click' reactions. The latter reaction involves the introduction of
      intradendritic 1,2,3-triazolyl ligands, which allows investigation of the
      selective role of these ligands in intradendritic Au(III) coordination and Au(0)
      nanoparticle stabilization. As a result, and using the various metallodendrimers
      with different oxidation states, small Au(0) nanoparticles are intradendritically
      stabilized by the triazole ligands, whereas with the related non-'click'
      dendrimers large Au(0) nanoparticles are formed outside the dendrimers and
      stabilized by a group of dendrimers. 

PMID- 24686342
TI  - Presentation and management of splenic injury after colonoscopy: a systematic
      review.
AB  - This study reviewed all single experience of splenic injuries after colonoscopy
      in the last 40 years to define the possible risk factors and the management of
      this complication. A MEDLINE and a PubMed search was undertaken to identify
      articles in English, French, Spanish, and Italian from 1974 to 2012 using the key
      words: "splenic injury," "splenic rupture," and "colonoscopy." Data were analyzed
      using descriptive statistic. A total of 103 cases have been described in 75
      reports. The majority of the patients were women (71.56%) and 6.85% underwent
      previous pelvic surgery. The mean age was 63 years (range, 29 to 90 y). About 61
      of the 103 studies (59.2%) reported the presence or the absence of previous
      abdominal surgery and within these, only 31 of 61 patients (50.82%) underwent
      previous abdominal surgery. In this review, over half of the patients with
      splenic injury underwent colonoscopy for routine surveillance (62.75%), and only
      one third of the splenic injures were associated with biopsy or polypectomy. The
      majority of patients (78.57%) developed symptoms within the first 24 hours after
      colonoscopy and in a minority of cases (21.43%), there was a delayed presentation
      24 hours after colonoscopy. Computed tomography was used as the primary modality
      to make the diagnosis in 69 of 98 cases (70.41%) and as a confirmatory test in
      many additional cases. Twenty-six of 102 patients (25.49%) were treated by
      conservative methods, whereas the majority of patients (69.61%) underwent
      splenectomy as a definitive treatment. Because of possible medicolegal
      implications, the endoscopists should consider mentioning splenic injury on the
      consent form of colonoscopy after bowel perforation and bleeding, particularly in
      higher risk patients. 

PMID- 24686341
TI  - Tissue engineering of tumor stromal microenvironment with application to cancer
      cell invasion.
AB  - 3D organotypic cultures of epithelial cells on a matrix embedded with mesenchymal
      cells are widely used to study epithelial cell differentiation and invasion. Rat
      tail type I collagen and/or matrix derived from Engelbreth-Holm-Swarm mouse
      sarcoma cells have been traditionally employed as the substrates to model the
      matrix or stromal microenvironment into which mesenchymal cells (usually
      fibroblasts) are populated. Although experiments using such matrices are very
      informative, it can be argued that due to an overriding presence of a single
      protein (such as in type I Collagen) or a high content of basement membrane
      components and growth factors (such as in matrix derived from mouse sarcoma
      cells), these substrates do not best reflect the contribution to matrix
      composition made by the stromal cells themselves. To study native matrices
      produced by primary dermal fibroblasts isolated from patients with a tumor prone,
      genetic blistering disorder (recessive dystrophic epidermolysis bullosa), we have
      adapted an existing native matrix protocol to study tumor cell invasion.
      Fibroblasts are induced to produce their own matrix over a prolonged period in
      culture. This native matrix is then detached from the culture dish and epithelial
      cells are seeded onto it before the entire coculture is raised to the air-liquid
      interface. Cellular differentiation and/or invasion can then be assessed over
      time. This technique provides the ability to assess epithelial-mesenchymal cell
      interactions in a 3D setting without the need for a synthetic or foreign matrix
      with the only disadvantage being the prolonged period of time required to produce
      the native matrix. Here we describe the application of this technique to assess
      the ability of a single molecule expressed by fibroblasts, type VII collagen, to
      inhibit tumor cell invasion. 

PMID- 24686340
TI  - The psychologist as an interlocutor in autism spectrum disorder assessment:
      insights from a study of spontaneous prosody.
AB  - PURPOSE: The purpose of this study was to examine relationships between prosodic
      speech cues and autism spectrum disorder (ASD) severity, hypothesizing a mutually
      interactive relationship between the speech characteristics of the psychologist
      and the child. The authors objectively quantified acoustic-prosodic cues of the
      psychologist and of the child with ASD during spontaneous interaction,
      establishing a methodology for future large-sample analysis. METHOD: Speech
      acoustic-prosodic features were semiautomatically derived from segments of
      semistructured interviews (Autism Diagnostic Observation Schedule, ADOS; Lord,
      Rutter, DiLavore, & Risi, 1999; Lord et al., 2012) with 28 children who had
      previously been diagnosed with ASD. Prosody was quantified in terms of
      intonation, volume, rate, and voice quality. Research hypotheses were tested via
      correlation as well as hierarchical and predictive regression between ADOS
      severity and prosodic cues. RESULTS: Automatically extracted speech features
      demonstrated prosodic characteristics of dyadic interactions. As rated ASD
      severity increased, both the psychologist and the child demonstrated effects for
      turn-end pitch slope, and both spoke with atypical voice quality. The
      psychologist's acoustic cues predicted the child's symptom severity better than
      did the child's acoustic cues. CONCLUSION: The psychologist, acting as evaluator
      and interlocutor, was shown to adjust his or her behavior in predictable ways
      based on the child's social-communicative impairments. The results support future
      study of speech prosody of both interaction partners during spontaneous
      conversation, while using automatic computational methods that allow for scalable
      analysis on much larger corpora.

PMID- 24686343
TI  - A comparative review between laparoscopic and robotic pancreaticoduodenectomies.
AB  - In pancreatic surgery, there is an increasing interest in the feasibility of
      minimal access techniques. Robotic surgery has improved some limitations of
      standard laparoscopy and it is expected as a promising access. We provide a
      comparative review between laparoscopic and robotic pancreaticoduodenectomies.
      Between 1996 and 2013, we found 284 patients in the laparoscopic group and 147 in
      the robotic. Operative time, morbidity, and mortality were similar for both the
      groups (425.94 min, 30.28%, 2.19% in the laparoscopic group and 415.88 min,
      36.78%, and 2.72% for the robotic arm, respectively). The mean hospital stay,
      mean estimated blood loss, fistula, and conversion rates were 11.09 days, 172,93
      mL, 13.02%, and 5.63% and 13.84 days, 346.44 mL, 27.69%, and 11.56% for the
      laparoscopic and robotic group, respectively (P<0.05). Laparoscopic
      pancreaticoduodenectomy may confer benefits over robotic
      pancreaticoduodenectomies, although it is expected that outcomes of both
      modalities are likely to improve with greater experience and better patient
      selection. 

PMID- 24686344
TI  - Strategies to reduce pancreatic stump complications after open or laparoscopic
      distal pancreatectomy.
AB  - Fibrin sealants could potentially protect against the occurrence of pancreatic
      fistula after distal pancreatectomy (DP). Fourteen relevant clinical studies (11
      open and 3 laparoscopic DP) were identified using an extensive customized
      literature search, including 4 randomized controlled trials. Data from the 1
      prospective randomized controlled trial with reasonable patient numbers found
      that fibrin reinforcement of the pancreatic stump suture line in open DP was
      associated with a significant reduction in fistula rate compared with suturing
      alone. Three other studies failed to show a significant difference in fistula
      rate. Two small scale nonrandomized retrospective studies each reported a reduced
      fistula rate associated with use of fibrin sealant in laparoscopic DP. On the
      basis of the current studies to evaluate the use of fibrin sealants in open and
      laparoscopic DP, application of fibrin glue to the pancreatic stump could help to
      reduce the incidence of troublesome pancreatic fistulas associated with this
      procedure. 

PMID- 24686345
TI  - Fast-track versus standard care in laparoscopic high anterior resection: a
      prospective randomized-controlled trial.
AB  - The value of fast-track (FT) multimodal recovery programs in improving
      hospitalization of surgical patients has been widely proved. The application of
      FT protocols to laparoscopic colorectal surgery seems to maximize the effects of
      the minimally invasive approach. The objectives of this randomized-controlled
      trial are to compare the short-term outcomes (bowel function, return to oral
      nutrition, day of discharge, fatigue, time to resume normal activities,
      functional capabilities, and readmission rate) of patients undergoing elective
      laparoscopic high anterior resection (HAR) following either a FT or a standard
      program. The prospective randomized-controlled trial included 52 consecutive
      patients undergoing elective laparoscopic HAR. Group 1 was treated with a FT
      rehabilitation program, and group 2 was treated with a standard care (SC)
      program. Patients were interviewed 14 and 30 days postoperatively. One patient in
      each group was excluded from the study. Mean hospital stay, time of first bowel
      movement, and bowel function resumption were significantly shorter in the FT
      group (P<0.05). Patients in the FT group referred more pain in day 0 versus
      patients in the SC group (P<0.05) even though the difference disappeared from day
      1. Fatigue was significantly reduced at day 14 in the FT group compared with the
      SC group (P<0.01). Similarly, ability to resume the normal preoperative attitude
      (walking stairs, cooking, housekeeping, shopping, and walking outdoors) was
      significantly better at day 14 in the FT group (P<0.005). There was no
      significant difference between the 2 groups at day 30 for the same parameters.
      There were no readmissions in both the groups and no need for consultations from
      general practitioners. FT multimodal program is a safe approach effective on
      postoperative short-term outcome significantly reducing hospital stay. Early
      postoperative pain control needs to be optimized. 

PMID- 24686346
TI  - Morphology, localization, and patterns of ghrelin-producing cells in stomachs of
      a morbidly obese population.
AB  - BACKGROUND: The role of the hormone ghrelin in the pathogenesis of morbid obesity
      is unclear. Researchers have identified its involvement in multifunctional
      activities that include appetite regulation, intestinal motility, release of
      growth hormone, and cell proliferation. The purpose of this study is to
      investigate and distinguish a pattern, if present, in ghrelin-producing cells and
      to record their distribution and quantity in a heterogenic morbidly obese
      population. SETTING: The Bariatric & Metabolic Institute, Section of Minimally
      Invasive Surgery, Cleveland Clinic Florida, Weston, FL. MATERIALS AND METHODS:
      Thirty-six patients who underwent sleeve gastrectomy for morbid obesity were
      evaluated for number and distribution of gastric ghrelin. Sections of fundus,
      body, and antrum were evaluated by using a ghrelin antibody staining technique.
      The gross specimens were divided into the following 3 zones: (1) fundus; (2)
      body; and (3) antrum. Three sections were then submitted from each zone. The
      ghrelin cells were counted using an image analyzer (MetaMorph; Universal Imaging
      Corporation, Downingtown, PA) after staining the blocks with antighrelin
      antibody. Counting ghrelin cells was standardized, and for each section 10 high
      power fields were examined at *4000. Our statistical analysis entailed a Student
      t test to compare the number of cells by age, sex, race, diabetic/nondiabetic,
      and body mass index. A P-value <0.05 was considered statistically significant.
      RESULTS: Thirty-six patients (female 20/male 16) were studied. The average age of
      these patients was 45.6 (18 to 71) years. Race distribution was as follows:
      whites, 50% (18); African American, 13.9% (5); and Hispanic, 36.1% (13). Patients
      with diabetes comprised 13.9% of the cohort (5). Average body mass index was 44.9
      kg/m (31 to 70). Significant differences in ghrelin cell distribution were found
      when comparing gastric anatomy location. Ghrelin cells were significantly more
      abundant in the gastric fundus when compared with the body and the antrum.
      Quantities of cells in the antrum were significantly higher in the Hispanic
      population (P=0.0054). No significant differences among other groups were
      observed. CONCLUSIONS: In conclusion, ghrelin-producing cells seem to be more
      abundant in the fundus of morbidly obese patients. No significant differences
      were found in terms of number of cells by age, sex, presence of diabetes, or body
      mass index. There was an incidental finding of a higher concentration of these
      cells located in the antrum of the Hispanic population when compared with the
      white cohort.

PMID- 24686347
TI  - Comparison of standard-pressure and low-pressure pneumoperitoneum in laparoscopic
      cholecystectomy: a double blinded randomized controlled study.
AB  - BACKGROUND AND OBJECTIVE: With the safety of laparoscopic cholecystectomy (LC)
      having been established, the current stress is on reducing the postoperative
      morbidity associated with this procedure. Hence, this study was undertaken to
      compare the effect of low-pressure (8 mm Hg) (LPLC) versus standard-pressure (12
      mm Hg) (SPLC) pneumoperitoneum on postoperative pain, respiratory and liver
      functions, the stress response, and the intraoperative surgeon comfort in
      patients undergoing LC. MATERIALS AND METHODS: Patients undergoing LC (n=43) were
      randomized into the LPLC (8 mm Hg) group (n=22) and the SPLC (12 mm Hg) group
      (n=21). Postoperative pain, changes in liver function, peak expiration flow rate,
      C-reactive protein level, and intraoperative surgeon comfort were assessed.
      RESULTS: The postoperative pain scores (P=0.003, 0.000, 0.001, and 0.002 at 0, 4,
      8, and 24 h), total analgesic requirement (P=0.001), and the number (total and
      good) of demands for analgesic in the first 24 hours (P=0.002 and 0.001) were
      lower in the LPLC group. The surgeon comfort in the LPLC group was significantly
      lesser (P=0.000). The liver function and peak expiration flow rate did not show
      any significant changes. C-reactive protein levels varied significantly only at
      24 hours postoperatively (P=0.001). CONCLUSIONS: The use of low-pressure
      pneumoperitoneum (8 mm Hg) for LC is associated with a significantly lower
      postoperative pain. However, the use of this low-pressure pneumoperitoneum can
      jeopardize the surgeon's comfort.

PMID- 24686348
TI  - Laparoscopic repair of perforated peptic ulcers: the sutured omental patch and
      focused sequential lavage technique.
AB  - We propose a standardized technique of repair and lavage with the outcomes of 50
      consecutive patients treated at our institution. The perforation was closed
      primarily and reinforced with omental patch. It was then followed by peritoneal
      lavage in a focused sequential manner that involved quadrant to quadrant lavage
      with tilting of operating table and changing of position between the surgeon and
      the camera surgeon. None of our patients had postoperative intra-abdominal
      complications, but unfortunately 1 patient succumbed to respiratory
      complications. Respiratory complications was the most common postoperative
      complication in our series (9 patients), whereas 2 patients had ileus. There were
      no leaks or reoperations in our series. Laparoscopic repair and sutured
      omentoplasty, followed by focused sequential lavage in a systematic manner, if
      performed diligently, will yield good outcomes. 

PMID- 24686349
TI  - The impact of mesh fixation with a collagen-fibrin sealant in a murine ventral
      hernia model.
AB  - INTRODUCTION: Pain and adhesions represent the challenge in hernia surgery. AIM:
      To investigate mesh fixation and adhesion prevention with a collagen-fibrin
      sealant. MATERIALS AND METHODS: Twenty-seven male Sprague-Dawley rats were
      operated twice, to create and repair 2 ventral hernias. Mesh fixation was with
      collagen-fibrin sealant on 1 side (group I), whereas an additional peritoneal
      suture was added in group II. On day 60 animals were killed and mesh migration,
      integration and number, grade and location of adhesions noted. RESULTS: Migration
      occurred in 12 (44.4%) in group 1 and 3 (11.1%) in group 2, P=0.023. Adhesions
      developed to 18 (33.3%) meshes. There was no difference in adhesion grade or area
      for mesh center or edge between the groups (P=0.735 and P=0.829, respectively).
      Median adhesion grade for mesh center was 1 and edge 3 (range, 0 to 4), P=0.005
      and P=0.001, respectively. Granuloma formation was noted in 8 (18.6%) animals;
      only with suture-fixed mesh. CONCLUSIONS: Mesh fixation with fibrin sealant is
      not satisfactory, however, adhesion prevention seems to be; adhesions to the edge
      of the mesh are most severe.

PMID- 24686350
TI  - Standardized laparoscopic sphincter-preserving total mesorectal excision for
      rectal cancer: long-term oncologic outcome in 217 unselected consecutive
      patients.
AB  - PURPOSE: This study was designed to evaluate the impact of a standardized
      laparoscopic total mesorectal excision (TME) on the long-term oncologic outcome
      of unselected patients with rectal cancer (RC). METHODS: Unselected consecutive
      patients with histologically proven RC underwent a standardized laparoscopic TME
      with medial to lateral approach encompassing 9 sequential steps: (1) ligation of
      inferior mesenteric vessels, (2) mobilization of the left colon and sigmoid colon
      (medial to lateral), (3) posterior dissection of the rectum, (4) lateral
      mobilization of the sigmoid, left colon, and splenic flexure, (5) left and right
      side dissection of the rectum, (6) anterior dissection of the rectum, (7)
      transection of the rectum, (8) delivery of the specimen, and (9) colorectal
      anastomosis. RESULTS: From 2005 to June 2012, laparoscopic sphincter-preserving
      TME was attempted in 217 patients with a 6.5% conversion rate. There were 91
      women and 126 men, aged 58.3 years (range, 22 to 84 y), with body mass index of
      26.10 (range, 20 to 45), operative time was 150.4 minutes (range, 60 to 330 min),
      and 24.7 (range, 4 to 98) lymph nodes were harvested. Length of stay was 7.56
      days (range, 3 to 32 d). Complication rate was 17.05%. The mean follow-up time of
      all patients was 36.12 months (range, 1 to 89 mo). Local recurrence rate was 3.6%
      and distant recurrence rate was 8.7%. The 5-year disease-free survival rates were
      81.5%. CONCLUSIONS: A standardized laparoscopic sphincter-preserving TME resulted
      in a favorable short-term outcome in unselected patients with RC.

PMID- 24686351
TI  - Laparoscopic surgery for stage IV colorectal cancer.
AB  - Laparoscopic surgery (Lap) is a feasible therapy in advanced colorectal cancer
      (CRC) without distant metastasis. Resection of primary lesion in stage IV CRC is
      now recognized as part of multimodal therapy. However, technical safety and
      invasiveness of Lap in stage IV CRC remain controversial. The feasibility of Lap
      in stage IV CRC was determined. Clinical outcomes were compared in primary
      colorectal resection using Lap, open surgery (Opn), and radical Lap for stages I
      to III CRC. No difference was observed regarding estimated blood loss and
      operative time between procedures. Postoperative recovery time and time to
      subsequent secondary therapy in the stage IV Lap group were significantly shorter
      than those in the Opn group. Similar results were observed for the 3-year overall
      survival rate. Lap for stage IV CRC is feasible and preferable in terms of
      technical safety and invasiveness. It may be useful in multimodal therapy for
      stage IV CRC. 

PMID- 24686352
TI  - Thoracoscopic esophagectomy in the prone position versus in the lateral position
      for patients with esophageal cancer: a comparison of short-term surgical results.
AB  - AIM: Thoracoscopic esophagectomy (TE) in the prone position for patients with
      esophageal cancer has received a great deal of attention. We retrospectively
      compared clinical outcomes and surgical stress of TE in the prone position (TE-P)
      and in the lateral position (TE-L) at our institution. METHODS: A total of 58
      consecutive patients (28 in the TE-L group and 30 in the TE-P group) were
      studied. Between the 2 groups, clinical outcomes and various parameters were
      compared. RESULTS: There were no hospital deaths in both TEL and TEP groups.
      Blood loss during the thoracoscopic part of the surgery were significantly
      (P<0.01) lower in the TE-P group (118+/-72 mL) compared with the TE-L (245+/-203
      mL) group. The incidence of respiratory complications tended to be lower (P=0.07)
      in the TE-P group (3.3%) than in the TE-L (17.8%) group. The duration of systemic
      inflammatory response syndrome condition was significantly (P=0.02) shorter in
      the TE-P group (1.5+/-2.5 d) than in TE-L (3.6+/-3.5 d) group. The levels of
      serum C-reactive protein on postoperative days 1 and 2 were significantly
      (P<0.01) lower in the TE-P group than in the TE-L group. CONCLUSIONS: TE-P for
      patients with esophageal cancer was safe and feasible. TE-P might be a
      potentially less invasive procedure than TE-L.

PMID- 24686353
TI  - High rate of post-ERCP pancreatitis in patients undergoing endoscopic treatment
      of benign biliary stricture.
AB  - INTRODUCTION AND AIM: Endoscopic treatment is the best option for patients with
      postsurgical stricture of main biliary duct. There is scarce information about
      the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP)
      complications in this condition. The aim was to evaluate the incidence of
      complications and the associated risk factors in patients undergoing ERCP for
      postcholecystectomy biliary stricture. MATERIALS AND METHODS: Prospective
      analysis of patients with postsurgical stenosis of main biliary duct was carried
      out. Rate of post-ERCP complications was determined and the associated risk
      factors were analyzed. RESULTS: A total of 25 patients were included. The success
      rate of endoscopic treatment was 92% (n=23). Two patients had recurrence of
      stricture with median follow-up of 23 months (range, 0.3 to 65.4 mo). Five
      patients (20%) developed acute pancreatitis after ERCP. No risk factors were
      detected in multivariate analysis. CONCLUSION: Incidence of post-ERCP
      pancreatitis is high in patients with biliary stricture associated with surgical
      procedures.

PMID- 24686354
TI  - Laparoscopic repair of ventral hernia in a laparoscopic experienced surgical
      center: low recurrence rate, morbidity, and chronic pain are achievable.
AB  - PURPOSE: Recurrence rate and the perioperative outcome evaluation through
      laparoscopic approach for ventral (primary and incisional) hernia repair.
      MATERIALS AND METHODS: A retrospective evaluation of a series of patients treated
      through a minimally invasive approach for ventral hernia was performed. A
      standardized surgical technique was adopted. All the patients were evaluated
      through a clinical follow-up. RESULTS: From July 2004 to June 2011, 150
      videolaparoscopic ventral hernia repairs were performed. The median follow-up was
      40 months. One hernia recurrence (0.7%) was detected after 55 months. The
      intraoperative and postoperative complication rate was 2.6% (1 conversion to open
      surgery) and 5.3%, respectively. Chronic pain nonresponsive to drug was
      registered in 2 patients (1.3%). CONCLUSIONS: The videolaparoscopic approach to
      ventral hernia repair is a safe technique that can guarantee a low recurrence
      rate; moreover, if it is performed in an experienced laparoscopic surgical
      center, it can be a valid alternative to the traditional open approach.

PMID- 24686355
TI  - Laparoscopic cholecystectomy in patients aged 80 years and older: an analysis of
      111 patients.
AB  - INTRODUCTION: The incidence of cholelithiasis increases with age. More
      octogenarian (>=80 y) patients are undergoing laparoscopic cholecystectomy (LC)
      operation throughout the world. PATIENTS AND METHODS: A retrospective study was
      conducted on patients older than 80 years (group 1: 111 patients) and those in
      the 18 to 79 years age group (group 2: 185 patients), who underwent LC between
      July 2005 and October 2009. The variables analyzed were the presentation,
      demographics, comorbid illnesses, American Society of Anaesthesiology (ASA)
      scores, history of previous abdominal surgery, the operative time, postoperative
      morbidity and mortality, and the length of hospital stay. A comparison was made
      between the two groups. Data was evaluated by using the chi and the Fisher exact
      test. P<0.005 was considered significant. RESULTS: The difference in both groups
      in the mean age and ASA scores were significant. The indication for LC was
      gallstone disease in 87 (78.4%) patients, acute cholecystitis in 16 (14.4%), and
      gallstone pancreatitis in 8 (7.2%) of group 1 patients. The conversion rate was
      not statistically significant. The mean operative time was 77 minutes in group 1
      patients, and this was significantly longer than that of group 2 patients. The
      postoperative oral intake within 24 hours of surgery was significantly earlier in
      group 2 patients. Other parameters were not significantly different between the 2
      groups. CONCLUSIONS: LC in octogenarians is a relatively safe procedure that can
      be performed with low morbidity and mortality rates. The comorbidities and higher
      ASA scale are major risk factors for postoperative complications in this age
      group of patients.

PMID- 24686356
TI  - Laparoscopic gastrectomy in patients with previous gastrectomy for gastric
      cancer: a report of 17 cases.
AB  - BACKGROUND: Laparoscopic gastrectomy (LAG) is increasingly used as a treatment
      for gastric cancer. However, it is contraindicated in patients with previous
      abdominal surgery, because of a higher risk of enteric injury, technical
      difficulties associated with adhesions, and longer operative times. The aim of
      this study was to assess the feasibility and clinical outcomes of LAG in patients
      who had previously undergone gastrectomy for gastric cancer. MATERIALS AND
      METHODS: Between June 2008 and May 2012, we performed laparoscopic gastrectomies
      in 17 patients with remnant stomach cancer who had previously undergone open
      gastrectomy (10 patients) or LAG (7 patients) for early gastric cancer. We
      performed laparoscopic distal gastrectomies with Roux-en-Y gastrojejunostomy in
      10 patients, and laparoscopic total gastrectomies in 7 patients. RESULTS: None of
      the patients required conversion to open surgery or intraoperative transfusion.
      One patient with postoperative bleeding received a transfusion of 4 U of blood.
      There were 2 cases of serious postoperative complications: 1 internal herniation
      and 1 anastomosis leakage. One patient experienced tractitis at the trocar site.
      All patients had tumor-free resection margins, and there were no mortalities.
      CONCLUSION: LAG is a safe and realistic treatment for patients who have
      previously undergone gastrectomy, although it may be associated with an increased
      need for adhesiolysis and longer surgery times.

PMID- 24686357
TI  - Minimally invasive management of postoperative esophagojejunal anastomotic leak.
AB  - PURPOSE: Postoperative esophagojejunal fistula induces morbidity and mortality
      after total gastrectomy and affects the long-term survival rate. METHODS: Between
      2003 and 2011, 38 patients underwent laparoscopic total gastrectomy and 2
      developed an esophagojejunal fistula. RESULTS: The diagnosis was established by a
      computed tomography scan with contrast ingestion. The absence of complete
      dehiscence and the vitality of the alimentary loop were checked during
      laparoscopic exploration, associated with effective drainage. During the
      endoscopy, dehiscence was assessed and a covered stent and nasojejunal tube were
      inserted for enteral feeding. The leaks healed progressively, oral feeding was
      resumed and the drains removed within 3 weeks. The stent was removed 6 weeks.
      Three months later, the patients were able to eat without dysphagia. CONCLUSIONS:
      Early diagnosis allows successful conservative management. The objectives are
      effective drainage, covering by an endoscopic stent and renutrition. Management
      by a multidisciplinary team is essential.

PMID- 24686358
TI  - Can percutaneous cholecystostomy be a definitive management for acute
      cholecystitis in high-risk patients?
AB  - PURPOSE: To evaluate the efficacy, long-term outcome, and safety of percutaneous
      cholecystostomy (PC) in high-risk surgical patients. METHODS: This was a
      retrospective descriptive review of the medical records of 36 patients who
      underwent PC for acute cholecystitis (AC) at a single institution between 2000
      and 2011. Primary outcomes were overall morbidity, mortality, and need for
      interval cholecystectomy. RESULTS: PC was initially successful, and symptoms
      disappeared within 3 days in all patients. Seven patients (2 during
      hospitalization and 5 during follow-up) died, 6 for a reason unrelated to AC, and
      1 succumbed to a sepsis-related condition caused by uncontrolled cholecystitis
      progression. Elective cholecystectomy was performed in 6 patients. PC was a
      definitive treatment in 63.9% of patients. CONCLUSIONS: PC is a safe and
      efficient treatment option for patients with AC who are less eligible for
      surgery. After patients recover from PC, further treatment such as
      cholecystectomy may not be needed.

PMID- 24686359
TI  - Laparoscopic sigmoidectomy using a hemi-double-stapling technique.
AB  - BACKGROUND: The double-stapling technique (DST) is frequently used in
      laparoscopic sigmoidectomy. Unfortunately, anastomotic leakage after laparoscopic
      intracorporeal colorectal anastomosis with DST is seen with some frequency.
      METHODS: We performed DST on 40 patients (June 2007 to August 2008) and hemi-DST
      on 50 patients (September 2008 to December 2011) undergoing laparoscopic
      sigmoidectomy. RESULTS: There were no occurrences of anastomotic leakage in the
      hemi-DST group, and 2 instances of anastomotic leakage in the DST group were
      observed. In these patients, the leakage appeared at the lateral intersecting
      anastomotic margins. CONCLUSIONS: Using the hemi-DST for laparoscopic
      intracorporeal colorectal anastomosis will make laparoscopic sigmoidectomy a
      safer procedure.

PMID- 24686360
TI  - Use of fibrin glue for fixation of mesh and approximation of Peritoneum in
      Transabdominal Preperitoneal (TAPP) inguinal hernia repair: technical feasibility
      and early surgical outcomes.
AB  - BACKGROUND: It is a common practice to secure both mesh and peritoneum using
      tacks when performing a transabdominal preperitoneal (TAPP) inguinal hernia
      repair. The use of tacks to secure the mesh is well documented and has been
      associated with postoperative chronic pain. Recently, fibrin glue has been used
      to secure the mesh in these repairs but not used to reapproximate the incised
      peritoneum. This study assessed the technical feasibility of using fibrin glue
      for fixation of both mesh and peritoneum. PATIENTS AND METHODS: A total of 33
      TAPP hernia repairs were carried out in 27 consecutive patients. In all the
      patients, both mesh and peritoneum were secured with fibrin glue (20 primary
      inguinal hernia repairs, 5 bilateral hernia repairs, 1 recurrent inguinal hernia,
      and 1 recurrent bilateral hernia repair). RESULTS: Patients were followed up at
      an outpatient clinic between the second and third week after surgery. Six
      patients were followed up through telephone. Patients were questioned on the
      following factors: residual postoperative pain (groin and port sites), unplanned
      GP or hospital visits, employment status and number of days between their surgery
      and return to both work and normal activities, and recurrence. No patients had
      residual groin or port site pain at a median of 21 days after surgery. No patient
      required an unplanned follow-up appointment with their GP. One patient (recurrent
      repair) developed a seroma postoperatively. Median time to normal activities was
      10 days (range, 3 to 21 d). CONCLUSIONS: Total glue fixation of mesh and
      peritoneum is technically feasible and early results show low rates of
      postoperative complications and pain. Randomized studies are needed to confirm
      this.

PMID- 24686361
TI  - Laparoscopic bowel-lifting technique: a novel and standardized technique for
      laparoscopic low anterior resection for rectal cancer.
AB  - INTRODUCTION: Although surgeons have tried to reduce the number of ports in order
      to achieve better cosmesis and less postoperative pain, it may lead to increased
      risk for complications. Herein, we introduce a technique, "laparoscopic bowel
      lifting (LBL) technique," which helps to reduce ports without additional trocars.
      METHODS: The mesocolon is pierced near the line of transaction using the pair of
      dissecting forceps. A 1-0 Vicryl suture is introduced into the abdominal cavity
      using a grasping needle and passed through the mesocolon. The colon is retracted
      using the suture and fixed to the abdominal wall using a pair of forceps.
      Thereafter, traction is placed on the main nutrient artery. Mobilization of the
      rectum is performed after moving the traction to the cranial side by using a
      grasping needle. As the rectal tube was pulled toward the cranial side, it is
      possible to identify the mesorectum with a good visual field. RESULTS: We
      performed this procedure in 100 consecutive patients with rectal cancer who
      underwent curative laparoscopic low anterior resection (Lap-LAR) between November
      2001 and March 2010. The median duration of follow-up after Lap-LAR was 53.2
      months. The tumor was located in the middle rectum in 75 patients and in the
      lower rectum in 25 patients. The stage grouping on the basis of the TNM
      classification was as follows: stage 0, 6; stage I, 46; stage II, 18; and stage
      III, 30. The number of trocars used in the LBL group was 3 or 4. No LBL cases
      used 5 trocars. No operative complications were attributable to this technique.
      The overall rates of anastomotic leakage and morbidity were 10.0% and 33.0%,
      respectively. The 5-year relapse-free and 5-year overall survival rates were
      stage 0, 100/100; stage I, 93.3/96.8; stage II, 81.5/88.5; and stage III,
      74.5/75.7. CONCLUSIONS: LBL technique is feasible for performing Lap-LAR. This
      method reduces the number of ports and might help to introduce a single
      incisional surgery.

PMID- 24686362
TI  - Resectoscopic ablation of the gallbladder mucosa after cholecystostomy.
AB  - PURPOSE: To investigate the feasibility of endoscopic ablation of the gallbladder
      mucosa after cholecystostomy. MATERIALS AND METHODS: The mucosa of the
      gallbladder was endoscopically electrocoagulated through the cholecystostomy
      tract. After ablation, repeated luminal irrigation with chymotrypsin solution was
      given before removal of the tube. The patients were followed up by
      ultrasonography after the procedure. RESULTS: Twenty patients accepted this
      operation. The mean operating time was 38 minutes (range, 25 to 55 min). There
      were no procedure-related mortality and complications including perforation,
      bleeding, and cholangitis. Eighteen gallbladders have completely obliterated in 3
      months. The other 2 gallbladders developed asymptomatic retention cysts. During
      48 months of follow-up period, no stone occurred and no signs of malignancy were
      found at the site of the gallbladder. Seven patients died from the other medical
      illness. CONCLUSION: Resectoscopic ablation of the gallbladder mucosa is a safe
      and promising approach to sclerosis of the gallbladder after cholecystostomy.

PMID- 24686363
TI  - Thoracoscopic enucleation of esophageal submucosal tumor by prone position under
      artificial pneumothorax by CO2 insufflation.
AB  - Recently, the usefulness of the prone position for thoracoscopic esophagectomy
      has been demonstrated. Thoracoscopic resection of an esophageal submucosal tumor
      using a prone position also offers advantages over a lateral decubitus position.
      We describe 2 cases operated on using the prone position for the resection of
      esophageal submucosal tumor. Case 1 was a 35-year-old man, who was diagnosed with
      a 50*20 mm leiomyoma in the middle thoracic esophagus, and underwent right
      thoracoscopic tumor enucleation. Case 2 was a 61-year-old female, who had 45*30
      mm esophageal schwannoma in the lower thoracic esophagus with symptoms of
      dysphagia, and underwent left thoracoscopic tumor enucleation. No complication
      was observed in both cases. Thoracoscopic esophageal submucosal resection with
      prone position may add the merits to conventional decubitus position, such as
      superior visualization, and less bleeding. The side of incision should be
      determined according to the location of the tumor and anatomic rationality. 

PMID- 24686364
TI  - Multipurpose internal retractor for Single-incision surgery (SIS): single
      institution case series.
AB  - Single-incision laparoscopic surgery (SIS) is less invasive than standard
      laparoscopic surgery; however, it is more difficult due to restriction of motion
      and the impossibility to use assistants. To overcome these obstacles, we
      developed a self-sustaining multipurpose internal retractor by attaching a Lone
      Star retractor hook to a laparoscopic bulldog clamp. Herein, we report our SIS
      experience using our novel retractor. Between October 2008 and April 2011, 104
      patients underwent SIS using the internal retractor: 67 bandings (43%
      simultaneous hiatal hernia repair), 8 sleeve gastrectomies, 27 cholecystectomies,
      and 2 Nissen fundoplication. Mean age was 40 (range, 21 to 85) and mean body mass
      index was 40 kg/m (range, 20 to 64 kg/m). No intraoperative complications were
      observed from the use of the retractor but 2 cases required additional retraction
      due to liver size. This retractor has been successfully used for different SIS
      procedures showing to be safe, adaptable, and easy to use, lessening some
      challenges of SIS. 

PMID- 24686365
TI  - Use of fluorescence imaging technology to identify peritoneal endometriosis: a
      case report of new technology.
AB  - Indocyanine green has long been used to determine the vascularity of various
      anatomic structures. Endometriosis is a disease that features neovascularization
      as a part of its pathologic process. Presented is a case of detecting
      endometriosis with indocyanine green using the fluorescence imaging technology
      built into the daVinci Si surgical platform. 

PMID- 24686366
TI  - Celiac artery compression after a gastric bypass.
AB  - Median arcuate ligament (MAL) syndrome or celiac artery compression occurs
      secondary to diaphragmatic compression of the celiac artery and the corresponding
      neural structures of the celiac plexus. Typically, patients present with
      postprandial abdominal pain, nausea, vomiting, and weight loss. Diagnostically,
      various radiologic studies are used to document impingement of the celiac artery
      including ultrasound, computed tomography, aortograms, and magnetic resonance
      imaging. Historically, open approaches to the aorta and the celiac artery are
      performed to release the MAL and relieve compression of the celiac artery and the
      plexus. Laparoscopic approaches are now utilized to divide the MAL. This study
      describes a patient who underwent a successful laparoscopic Roux-en-Y gastric
      bypass and lost 100 lbs over a 2-year postoperative period. Subsequently, the
      patient developed postprandial abdominal pain associated with nausea. She
      underwent a computed tomogram that diagnosed celiac compression and then a
      dynamic ultrasound that showed elevated velocities with deep expiration.
      Ultimately, a laparoscopic MAL release with division of the celiac plexus was
      performed. At 10 months postoperatively, the patient remains asymptomatic. To our
      knowledge, this report documents a rare case of CAC after Roux-en-Y gastric
      bypass. On the basis of this report, CAC should be considered in the differential
      diagnosis of postprandial abdominal pain in patients after bariatric surgery. 

PMID- 24686367
TI  - A recurrence of benign multicystic peritoneal mesothelioma treated through
      laparoscopic excision: a case report and review of the literature.
AB  - Benign multicystic peritoneal mesothelioma is a rare cystic tumor with
      approximately 140 cases reported to date. It is found mainly in women of
      reproductive age and is commonly attached to the serosal surface of pelvic
      viscera. The pathogenesis is uncertain and debate regarding its neoplastic or
      reactive nature exists. The presenting symptoms are often nonspecific and most
      commonly include vague lower abdominal pain and fullness. Imaging studies are
      used to identify the lesion, but histologic studies with the aid of
      immunohistochemical techniques are needed for definitive diagnosis as the
      differential diagnosis is quite extensive. Surgical resection is the primary form
      of treatment, and follow-up is important due to the high rate of recurrence and
      the rare possibility of malignant transformation. Here, we present a case of a 50
      year-old female with a recurrence of benign multicystic peritoneal mesothelioma
      treated through laparoscopic excision and also a review of the literature. 

PMID- 24686368
TI  - Needle before the knife: nonoperative management of pneumoperitoneum with image
      guided aspiration after gastrointestinal perforation.
AB  - This case series documents the management of 3 acute gastrointestinal
      perforations secondary to upper endoscopic procedures and presents the use of
      nonoperative management with percutaneous aspiration in lieu of immediate
      surgical intervention. A growing number of endoscopists are using more advanced
      resection techniques, further potentiating the risk of gastrointestinal injury,
      including perforation. When localized perforations occur, endoscopic management
      has become an effective treatment option. Perforations that cannot be localized,
      sealed, or successfully treated with endoscopic closure have traditionally
      required an exploratory laparotomy. However, this series suggests that
      nonoperative management with percutaneous procedures may be successfully utilized
      in select patients. In 2 of the cases reported, no closure techniques were used
      and expectant management resulted in successful outcomes. This study suggests
      that the use of image-guided aspiration and serial abdominal exams can be
      utilized successfully in select patients. Image-guided needle aspiration of
      pneumoperitoneum can decrease patient discomfort and allow reliable serial
      physical examination, potentially eliminating unnecessary surgery. 

PMID- 24686369
TI  - A bleeding esophagopulmonary fistula: rare complication of stasis ulcer in
      refractory achalasia.
AB  - Achalasia refractory to Heller cardiomyotomy is a rare problem. Complications
      arising from long-standing achalasia include perforation because of stasis ulcers
      and malignancy. Here, we report a case of refractory achalasia presenting with
      recurrent hematemesis because of a perforated stasis ulcer leading to a bleeding
      esophagopulmonary fistula. 

PMID- 24686370
TI  - Lower NIH stroke scale scores are required to accurately predict a good prognosis
      in posterior circulation stroke.
AB  - BACKGROUND: The NIH stroke scale (NIHSS) is an indispensable tool that aids in
      the determination of acute stroke prognosis and decision making. Patients with
      posterior circulation (PC) strokes often present with lower NIHSS scores, which
      may result in the withholding of thrombolytic treatment from these patients.
      However, whether these lower initial NIHSS scores predict better long-term
      prognoses is uncertain. We aimed to assess the utility of the NIHSS at
      presentation for predicting the functional outcome at 3 months in anterior
      circulation (AC) versus PC strokes. METHODS: This was a retrospective analysis of
      a large prospectively collected database of adults with acute ischemic stroke.
      Univariate and multivariate analyses were conducted to identify factors
      associated with outcome. Additional analyses were performed to determine the
      receiver operating characteristic (ROC) curves for NIHSS scores and outcomes in
      AC and PC infarctions. Both the optimal cutoffs for maximal diagnostic accuracy
      and the cutoffs to obtain >80% sensitivity for poor outcomes were determined in
      AC and PC strokes. RESULTS: The analysis included 1,197 patients with AC stroke
      and 372 with PC stroke. The median initial NIHSS score for patients with AC
      strokes was 7 and for PC strokes it was 2. The majority (71%) of PC stroke
      patients had baseline NIHSS scores <=4, and 15% of these 'minor' stroke patients
      had a poor outcome at 3 months. ROC analysis identified that the optimal NIHSS
      cutoff for outcome prediction after infarction in the AC was 8 and for infarction
      in the PC it was 4. To achieve >80% sensitivity for detecting patients with a
      subsequent poor outcome, the NIHSS cutoff for infarctions in the AC was 4 and for
      infarctions in the PC it was 2. CONCLUSION: The NIHSS cutoff that most accurately
      predicts outcomes is 4 points higher in AC compared to PC infarctions. There is
      potential for poor outcomes in patients with PC strokes and low NIHSS scores,
      suggesting that thrombolytic treatment should not be withheld from these patients
      based solely on the NIHSS. (c) 2014 S. Karger AG, Basel.

PMID- 24686371
TI  - Effects of residual lignin and heteropolysaccharides on the bioconversion of
      softwood lignocellulose nanofibrils obtained by SO2-ethanol-water fractionation.
AB  - The amount of residual lignin and hemicelluloses in softwood fibers was
      systematically varied by SO2-ethanol-water fractionation for integrated
      biorefinery with nanomaterial and biofuel production. On the basis of their low
      energy demand in mechanical processing, the fibers were deconstructed to
      lignocellulose nanofibrils (LCNF) and used as substrate for bioconversion. The
      effect of LCNF composition on saccharification via multicomponent enzymes was
      investigated at different loadings. LCNF digestibility was compared with the
      enzyme activity measured with a quartz crystal microbalance. LCNF hydrolysis rate
      gradually decreased with lignin and hemicellulose concentration, both of which
      limited enzyme accessibility. Enzyme inhibition resulted from non-productive
      binding of proteins onto lignin. Near complete LCNF hydrolysis was achieved, even
      at high lignin and hemicellulose content. Sugar yields for LCNF were higher than
      those for precursor SEW fibers, highlighting the benefits of high surface area in
      LCNF. 

PMID- 24686372
TI  - Comparison of sodium carbonate-oxygen and sodium hydroxide-oxygen pretreatments
      on the chemical composition and enzymatic saccharification of wheat straw.
AB  - Pretreatment of wheat straw with a combination of sodium carbonate (Na2CO3) or
      sodium hydroxide (NaOH) with oxygen (O2) 0.5MPa was evaluated for its
      delignification ability at relatively low temperature 110 degrees C and for its
      effect on enzymatic hydrolysis efficiency. In the pretreatment, the increase of
      alkali charge (as Na2O) up to 12% for Na2CO3 and 6% for NaOH, respectively,
      resulted in enhancement of lignin removal, but did not significantly degrade
      cellulose and hemicellulose. When the pretreated solid was hydrolyzed with a
      mixture of cellulases and hemicellulases, the sugar yield increased rapidly with
      the lignin removal during the pretreatment. A total sugar yield based on dry
      matter of raw material, 63.8% for Na2CO3-O2 and 71.9% for NaOH-O2 was achieved
      under a cellulase loading of 20FPU/g-cellulose. The delignification efficiency
      and total sugar yield from enzymatic hydrolysis were comparable to the previously
      reported results at much higher temperature without oxygen. 

PMID- 24686373
TI  - Relationship between anaerobic digestion of biodegradable solid waste and
      spectral characteristics of the derived liquid digestate.
AB  - The evolution of spectral properties during anaerobic digestion (AD) of 29 types
      of biodegradable solid waste was investigated to determine if spectral
      characteristics could be used for assessment of biological stabilization during
      AD. Biochemical methane potential tests were conducted and spectral indicators
      (including the ratio of ultraviolet-visible absorbance at 254nm to dissolved
      organic carbon concentration (SUVA254), the ratio of ultraviolet-visible
      absorbance measured at 465nm and 665nm (E4/E6), and the abundance of fluorescence
      peaks) were measured at different AD phases. Inter-relationship between organic
      degradation and spectral indicators were analyzed by principle component
      analysis. The results shows that from methane production phase to the end of
      methane production phase, SUVA254 increased by 0.16-10.93 times, the abundance of
      fulvic acid-like compounds fluorescence peak increased by 0.01-0.54 times, the
      abundance of tyrosine fluorescence peak decreased by 0.03-0.64 times. Therefore,
      these indicators were useful to judge the course of mixed waste digestion. 

PMID- 24686374
TI  - Depolymerization of organosolv lignin using doped porous metal oxides in
      supercritical methanol.
AB  - An isolated, solvent-extracted lignin from candlenut (Aleurites moluccana)
      biomass was subjected to catalytic depolymerization in the presence of
      supercritical methanol, using a range of porous metal oxides derived from
      hydrotalcite-like precursors. The most effective catalysts in terms of lignin
      conversion to methanol-soluble products, without char formation, were based on
      copper in combination with other dopants based on relatively earth-abundant
      metals. Nearly complete conversion of lignin to bio-oil composed of monomers and
      low-mass oligomers with high aromatic content was obtained in 6h at 310 degrees C
      using a catalyst based on a Cu- and La-doped hydrotalcite-like precursor. Product
      mixtures were characterized by NMR spectroscopy, gel permeation chromatography,
      and GC-MS. 

PMID- 24686375
TI  - Economic and environmental assessment of syrup production. Colombian case.
AB  - This work presents a techno-economic and environmental assessment of the glucose
      syrups production from sugarcane bagasse, plantain husk, cassava husk, mango
      peel, rice husk and corncobs. According to the economic analysis, the corncob had
      both, the lowest production cost (2.48USD/kg syrup) and the highest yield
      (0.61kgofsugars/kg of wet agroindustrial waste) due to its high content in
      cellulose and hemicellulose. This analysis also revealed that a heat integration
      strategy is necessary since the utilities consumption represent an important
      factor in the production cost. According to the results, the pretreatment section
      requires more energy in the syrup production in comparison with the requirements
      of other sections such as production and sugar concentration. The environmental
      assessment revealed that the solid wastes such as furfural and
      hydroxymethylfurfural affected the environmental development of the process for
      all the agroindustrial wastes, being the rice husk the residue with the lowest
      environmental impact. 

PMID- 24686376
TI  - Hydrothermal carbonization (HTC): near infrared spectroscopy and partial least
      squares regression for determination of selective components in HTC solid and
      liquid products derived from maize silage.
AB  - Near-infrared (NIR) spectroscopy was evaluated as a rapid method of predicting
      fiber components (hemicellulose, cellulose, lignin, and ash) and selective
      compounds of hydrochar and corresponding process liquor produced by hydrothermal
      carbonization (HTC) of maize silage. Several HTC reaction times and temperatures
      were applied and NIR spectra of both HTC solids and liquids were obtained and
      correlated with concentration determined from van-Soest fiber analysis, IC, and
      UHPLC. Partial least-squares regression was applied to calculate models for the
      prediction of selective substances. The model developed with the spectra had the
      best performance in 3-7 factors with a correlation coefficient, which varied
      between 0.9275-0.9880 and 0.9364-0.9957 for compounds in solid and liquid,
      respectively. Calculated root mean square errors of prediction (RMSEP) were 0.42
      5.06mg/kg. The preliminary results indicate that NIR, a widely applied technique,
      might be applied to determine chemical compounds in HTC solid and liquid. 

PMID- 24686377
TI  - [Treatment of hydrocele by a general surgeon practicing in a rural resource-poor
      setting in Africa].
AB  - Hydrocele in adults is a collection of peritesticular fluid between the parietal
      and visceral layers of the tunica vaginalis testis. An endemic disease in Africa,
      its cause is either idiopathic or a reaction to filariasis. In the absence of
      treatment, its volume increases spontaneously. The onset of symptoms justifies
      treatment. In tropical zones, surgery is the most effective treatment. The
      technique must be simple to perform, require few resources, and limit the risks
      of complication. Three surgical techniques should be used. In resource-poor
      practice conditions, fenestration and, to a lesser extent, plication are the
      techniques most appropriate when the tunica vaginalis is essentially healthy.
      Only resection is possible when it is damaged. 

PMID- 24686378
TI  - Electrorheological response of inorganic-coated multi-wall carbon nanotubes with
      core-shell nanostructure.
AB  - The effect of coating thickness and sequence on the multi-wall carbon nanotube
      (MWCNT) surface on electrorheological (ER) activity is investigated. Silica
      coated MWCNTs with different shell thicknesses and inorganic-coated MWCNTs with
      different shell sequences are fabricated using the sol-gel process. The
      morphology and elemental analyses of the core-shell structured MWCNTs were
      performed and the effect of coating thickness and coating materials on the MWCNT
      surface on ER and dielectric properties of inorganic-coated MWCNT suspensions
      have been analyzed from the measurement results of shear stress, viscosity,
      current density and permeability. The electrical conductivity of silica-coated
      MWCNTs decreases with an increase of the shell thickness. However, the dynamic
      yield stress and viscoelastic properties under an external electric field
      increased when the shell thickness reached 20 nm and then decreased with the
      thickness up to 40 nm. However, the titania-coated MWCNT suspension with a shell
      thickness of 40 nm showed the highest dynamic yield stress compared to the other
      core-shell structured MWCNT suspension at the same volume fraction. It has been
      found that the material of the outermost shell plays an important role in the ER
      performance. It has been concluded that the electrical conductivity and the
      permittivity of the MWCNTs can be controlled by adjusting the coating thickness
      and sequence of inorganic materials. 

PMID- 24686379
TI  - Genetic manipulation of cerebellar granule neurons in vitro and in vivo to study
      neuronal morphology and migration.
AB  - Developmental events in the brain including neuronal morphogenesis and migration
      are highly orchestrated processes. In vitro and in vivo analyses allow for an in
      depth characterization to identify pathways involved in these events. Cerebellar
      granule neurons (CGNs) that are derived from the developing cerebellum are an
      ideal model system that allows for morphological analyses. Here, we describe a
      method of how to genetically manipulate CGNs and how to study axono- and
      dendritogenesis of individual neurons. With this method the effects of RNA
      interference, overexpression or small molecules can be compared to control
      neurons. In addition, the rodent cerebellar cortex is an easily accessible in
      vivo system owing to its predominant postnatal development. We also present an in
      vivo electroporation technique to genetically manipulate the developing cerebella
      and describe subsequent cerebellar analyses to assess neuronal morphology and
      migration. 

PMID- 24686380
TI  - Network communities within and across borders.
AB  - We investigate the impact of borders on the topology of spatially embedded
      networks. Indeed territorial subdivisions and geographical borders significantly
      hamper the geographical span of networks thus playing a key role in the formation
      of network communities. This is especially important in scientific and
      technological policy-making, highlighting the interplay between pressure for the
      internationalization to lead towards a global innovation system and the
      administrative borders imposed by the national and regional institutions. In this
      study we introduce an outreach index to quantify the impact of borders on the
      community structure and apply it to the case of the European and US patent co
      inventors networks. We find that (a) the US connectivity decays as a power of
      distance, whereas we observe a faster exponential decay for Europe; (b) European
      network communities essentially correspond to nations and contiguous regions
      while US communities span multiple states across the whole country without any
      characteristic geographic scale. We confirm our findings by means of a set of
      simulations aimed at exploring the relationship between different patterns of
      cross-border community structures and the outreach index. 

PMID- 24686381
TI  - Learning of grammar-like visual sequences by adults with and without language
      learning disabilities.
AB  - PURPOSE: Two studies examined learning of grammar-like visual sequences to
      determine whether a general deficit in statistical learning characterizes this
      population. Furthermore, we tested the hypothesis that difficulty in sustaining
      attention during the learning task might account for differences in statistical
      learning. METHOD: In Study 1, adults with normal language (NL) or language
      learning disability (LLD) were familiarized with the visual artificial grammar
      and then tested using items that conformed or deviated from the grammar. In Study
      2, a 2nd sample of adults with NL and LLD were presented auditory word pairs with
      weak semantic associations (e.g., groom + clean) along with the visual learning
      task. Participants were instructed to attend to visual sequences and to ignore
      the auditory stimuli. Incidental encoding of these words would indicate reduced
      attention to the primary task. RESULTS: In Studies 1 and 2, both groups
      demonstrated learning and generalization of the artificial grammar. In Study 2,
      neither the NL nor the LLD group appeared to encode the words presented during
      the learning phase. CONCLUSION: The results argue against a general deficit in
      statistical learning for individuals with LLD and demonstrate that both NL and
      LLD learners can ignore extraneous auditory stimuli during visual learning.

PMID- 24686382
TI  - Molecular characterization of human T-cell lymphotropic virus type 1 full and
      partial genomes by Illumina massively parallel sequencing technology.
AB  - BACKGROUND: Here, we report on the partial and full-length genomic (FLG)
      variability of HTLV-1 sequences from 90 well-characterized subjects, including 48
      HTLV-1 asymptomatic carriers (ACs), 35 HTLV-1-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) and 7 adult T-cell leukemia/lymphoma (ATLL)
      patients, using an Illumina paired-end protocol. METHODS: Blood samples were
      collected from 90 individuals, and DNA was extracted from the PBMCs to measure
      the proviral load and to amplify the HTLV-1 FLG from two overlapping fragments.
      The amplified PCR products were subjected to deep sequencing. The sequencing data
      were assembled, aligned, and mapped against the HTLV-1 genome with sufficient
      genetic resemblance and utilized for further phylogenetic analysis. RESULTS: A
      high-throughput sequencing-by-synthesis instrument was used to obtain an average
      of 3210- and 5200-fold coverage of the partial (n = 14) and FLG (n = 76) data
      from the HTLV-1 strains, respectively. The results based on the phylogenetic
      trees of consensus sequences from partial and FLGs revealed that 86 (95.5%)
      individuals were infected with the transcontinental sub-subtypes of the
      cosmopolitan subtype (aA) and that 4 individuals (4.5%) were infected with the
      Japanese sub-subtypes (aB). A comparison of the nucleotide and amino acids of the
      FLG between the three clinical settings yielded no correlation between the
      sequenced genotype and clinical outcomes. The evolutionary relationships among
      the HTLV sequences were inferred from nucleotide sequence, and the results are
      consistent with the hypothesis that there were multiple introductions of the
      transcontinental subtype in Brazil. CONCLUSIONS: This study has increased the
      number of subtype aA full-length genomes from 8 to 81 and HTLV-1 aB from 2 to 5
      sequences. The overall data confirmed that the cosmopolitan transcontinental sub
      subtypes were the most prevalent in the Brazilian population. It is hoped that
      this valuable genomic data will add to our current understanding of the
      evolutionary history of this medically important virus.

PMID- 24686383
TI  - Entangled titanium fibre balls combined with nano strontium hydroxyapatite in
      repairing bone defects.
AB  - OBJECTIVE: To investigate the effect of entangled titanium fibre balls (ETFBs)
      combined with nano strontium hydroxyapatite (nano-Sr-HAP) on the repair of bone
      defects in vivo. MATERIALS AND METHODS: Twenty-four 6-month-old, specific
      pathogen-free, male Sprague-Dawley rats were used. Drill defects were created in
      bilateral femoral condyles. ETFBs combined with nano-Sr-HAP were selected
      randomly from 72 samples and implanted into the femoral bone defects of left
      legs, which served as the experimental group, while ETFBs without nano-Sr-HAP
      were implanted into right legs for comparison. The bone defects on both sides
      were X-rayed. The anteroposterior positions and histological procedures and
      evaluations of each sample were performed at 1, 2, 4 and 8 weeks post-surgery.
      RESULTS: Histological results showed that the ETBs allowed new bone to grow
      within their structure. Additionally, an increase in new bone was seen on the
      nano-Sr-HAP side compared to the control side. The results of histomorphometric
      analysis confirmed that the new bone formation on the left side gradually
      increased with time. There was a statistical increase in new bone at 2, 4 and 8
      weeks, and the differences between the two sides were statistically significant
      at weeks 4 and 8 (p < 0.05 for all comparisons). CONCLUSION: The results showed
      that ETFBs possess a unique 3-dimensional interconnective porous structure and
      have excellent biocompatibility, cell affinity and osteoconductivity, which makes
      them useful as scaffold materials for repairing bone defects. On the other hand,
      nano-Sr-HAP improved the bone defect-repairing capacity of the ETFBs, which
      showed osteoinductive properties.

PMID- 24686385
TI  - Malformation of incisor teeth in Grem2-/- mice.
AB  - GREMLIN 2 (GREM2)--formerly, protein related to Dan and cerberus (PRDC)-is a
      potent antagonist of the bone morphogenetic proteins 2 and 4, but little else in
      known about its functions. We found that Grem2(-/-) mice developed small deformed
      mandibular and maxillary incisors, indicating that GREMLIN2 is required for
      normal tooth morphogenesis. Although DEXA scans suggested that bone mineral
      density might be increased in Grem2(-/-) mice, histology did not reveal any
      evident bone phenotype. Grem2(-/-) mice did not display any other notable
      phenotypes evaluated in a high-throughput screening process that encompassed a
      range of immunologic, metabolic, ophthalmic, and behavioral parameters. Our
      findings indicate that Grem2 can be added to the growing list of genes that
      affect tooth development in mice.

PMID- 24686386
TI  - Diagnostic exercise: High mortality in a flock of chukar partridge chicks
      (Alectoris chukar) in California.
AB  - Mortality of 20% of a flock of 1000 chukar partridge chicks occurred over a 6
      week period in Northern California from August to September 2012. Affected birds
      were 2 to 42 days old and died without premonitory clinical signs or after
      showing ruffled feathers and anorexia for 24 to 72 hours. Three carcasses were
      submitted for necropsy, 2 birds had hemorrhagic tracheitis grossly, and all 3 had
      lymphoplasmacytic and histiocytic myocarditis with myocardial necrosis
      microscopically. The differential diagnoses and the diagnostic workup to achieve
      a final diagnosis are discussed. The detection of 2 zoonotic agents in these
      birds makes this an interesting case from a public health perspective. 

PMID- 24686388
TI  - Antleroma in a free-ranging white-tailed deer (Odocoileus virginianus).
AB  - A 2-year-old male free-ranging white-tailed deer (Odocoileus virginianus) was
      diagnosed with bilateral expansile tumors of antler origin. The deer was found
      dead by a landowner in High Springs, Florida. Two roughly spherical,
      multilobular, broad-based, bony, velvet-covered masses originated from each
      antler pedicle. These masses replaced or displaced many of the bones and soft
      tissues of the skull and extended through the left cribriform plate and the right
      petrous temporal bone, compressing portions of the brain. Microscopically, the
      masses closely resembled normal-growing antler, containing all the elements
      thereof but with areas of necrosis and hemorrhage suggestive of ischemi or
      trauma. Tumorlike outgrowths termed antleromas have been described in free
      ranging and captive cervids and typically are associated with disruptions in the
      seasonal rise and fall of circulating testosterone necessary for normal antler
      growth, casting, and regeneration. 

PMID- 24686387
TI  - rhesus cytomegalovirus (macacine herpesvirus 3)-associated facial neuritis in
      simian immunodeficiency virus-infected rhesus macaques (Macaca mulatta).
AB  - Peripheral neuropathies are common sequelae to human immunodeficiency virus (HIV)
      infection in humans and are due to a variety of mechanisms, including direct
      antiretroviral toxicity, HIV-mediated damage, immune-mediated disorders, and
      opportunistic viral infections. Rhesus macaques (Macaca mulatta) infected with
      simian immunodeficiency virus (SIV) remain the most consistent animal model for
      unraveling the pathogenesis of lentiviral-associated disease and its associated
      opportunistic infections. Rhesus cytomegalovirus (RhCMV) is the most common
      opportunistic viral infection in rhesus macaques infected with SIV and causes
      multiorgan pathology; however, its role in peripheral nerve pathology has not
      been explored. We have identified 115 coinfected cases with SIV and RhCMV, of
      which 10 cases of RhCMV-associated facial neuritis were found (8.7% prevalence).
      Histologic lesions were consistent in all cases and ranged from partial to
      complete obliteration of the nerves of the tongue, lacrimal gland, and other
      facial tissues with a mixed inflammatory population of neutrophils and
      macrophages, of which the latter commonly contained intranuclear inclusion
      bodies. Luxol fast blue staining and myelin basic protein immunohistochemistry
      confirmed the progressive myelin loss in the peripheral nerves. Bielschowsky
      silver stain revealed progressive loss of axons directly related to the severity
      of inflammation. Double immunohistochemistry with spectral imaging analysis
      revealed RhCMV-infected macrophages directly associated with the neuritis, and
      there was no evidence to support RhCMV infection of Schwann cells. These results
      suggest that peripheral nerve damage is a bystander effect secondary to
      inflammation rather than a direct infection of Schwann cells and warrants further
      investigations into the pathogenesis of RhCMV-induced peripheral neuropathy. 

PMID- 24686389
TI  - Survivin and related proteins in canine mammary tumors: immunohistochemical
      expression.
AB  - Survivin is reexpressed in most human breast cancers, where its expression has
      been associated with tumor aggressiveness, poor prognosis, and poor response to
      therapy. Survivin expression was evaluated in 41 malignant canine mammary tumors
      (CMTs) by immunohistochemistry, in relation to histological grade and stage, and
      correlated with that of some related molecules (beta-catenin, caspase 3, heat
      shock proteins) to understand their possible role in canine mammary
      tumorigenesis. An increase in nuclear survivin expression, compared with healthy
      mammary glands, was observed in CMTs, where nuclear immunolabeling was related to
      the presence of necrosis. No statistically significant relation was found between
      the expression of the investigated molecules and the histological grade or stage.
      The present study may suggest an important involvement of survivin in CMT
      tumorigenesis. Its overexpression in most of the cases evaluated might suggest
      that targeting survivin in CMTs may be a valid anticancer therapy. 

PMID- 24686391
TI  - Pleomorphic xanthoastrocytoma within the medulla oblongata of a young dog.
AB  - A 13-week-old male intact Poodle mix dog developed an acute onset of vestibular
      ataxia, tetraparesis, and vomiting. The patient presented ambulatory,
      tetraparetic, and ataxic with a head tilt to the left and a disconjugate
      nystagmus (rotary nystagmus with fast phase to the right in right eye and
      vertical nystagmus in left eye). There were absent postural reactions in the left
      pelvic and left thoracic limbs and decreased right-sided postural reactions.
      Magnetic resonance imaging demonstrated an intra-axial mass within the left
      midcaudal medulla oblongata. On gross dissection, there was a left-sided neoplasm
      in the medulla oblongata with surrounding hemorrhage. The histologic findings
      indicated that the mass was a pleomorphic xanthoastrocytoma. This tumor, an
      uncommon variant of an astrocytoma most often seen in children and young adult
      humans, has yet to be described in dogs. 

PMID- 24686390
TI  - Survey of cardiovascular pathology in wild urban Rattus norvegicus and Rattus
      rattus.
AB  - Norway (Rattus norvegicus) and black rats (Rattus rattus) are common commensal
      pests, yet little is known about the ecology of wild rats, including their
      natural diseases. We describe microscopic cardiovascular pathology in a subset of
      a sample of 725 wild urban rats. Changes observed in the pulmonary blood vessels
      (n = 199) included arteriolar medial hypertrophy (20.1%, n = 40) and blood vessel
      mineralization (19.1%, n = 38). Microscopic changes in the heart (n = 200)
      included myocarditis (33.5%, n = 67), fibrosis (6.0%, n = 12), mineralization
      (9.5%, n = 19), myocardial degeneration (22.0%, n = 44), and right ventricular
      hypertrophy (4.5%, n = 9). Rats with myocarditis, fibrosis, or myocardial
      degeneration were grouped into a composite variable: cardiomyopathy. Statistical
      analysis showed that the odds of being affected by cardiomyopathy were greater in
      male rats (odds ratio [OR] = 2.49; 95% confidence interval [CI] = 1.12-5.55) and
      heavier rats (OR = 1.14; 95% CI = 1.09-1.20). The odds of pulmonary arteriolar
      medial hypertrophy was greater in sexually mature rats (OR = 2.35; 95% CI = 0.75
      7.36), while the odds of pulmonary vessel mineralization were greater in heavier
      rats (OR = 1.07; 95% CI = 1.03-1.11) and in black rats (OR = 5.35; 95% CI = 1.62
      17.69) compared to Norway rats. To our knowledge, this is the first detailed
      description of pathology in the cardiovascular system of wild rats and
      demonstrates that cardiovascular disease is common. The impact of these lesions
      on individual and population health remains to be investigated. 

PMID- 24686392
TI  - Synthesis of yolk-shell HPW@Hollow silicalite-1 for esterification reaction.
AB  - HPW@Hollow S-1, a novel solid catalyst which can be reused in the synthesis of
      ethyl acetate, was successfully prepared by the ship-in-bottle approach. The
      catalyst simultaneously shows high activity that resembles homogeneous catalysts,
      and outstanding stability like that of heterogeneous catalysts. 

PMID- 24686394
TI  - Unintended consequences of a Medicaid prescription copayment policy.
AB  - BACKGROUND AND OBJECTIVES: Medication copayments can influence patient choices.
      We evaluated 2 copayment policies implemented by Massachusetts Medicaid
      incentivizing the use of selected generic medications. RESEARCH DESIGN AND
      MEASURES: In 2009, Massachusetts Medicaid copayments were $1 for generics and $3
      for brands. On February 1, 2009, copayments for generic antihypertensives,
      antihyperlipidemics, and hypoglycemics (target medications) remained at $1,
      whereas copayments for all nontarget generics increased to $2 (policy #1) and $3
      on July 1, 2010 (policy #2). Using state-level, aggregate prescription data, we
      developed interrupted time-series models with controls to evaluate the impact of
      these policies on use of target generics, target brands, and nontarget essential
      medications (defined as medications required for ongoing treatment of serious
      medical conditions). RESULTS: After policy #1, target generic use increased by
      0.93% (P<0.001) with a subsequent quarterly slope decrease of -0.16% (P<0.01);
      policy #2 led to a slope increase of 0.20% (P<0.01) for target generics; increase
      in target generics attributable to policy changes was 28,000 prescriptions per
      year. Neither policy affected target brand use. For nontarget essential generics,
      there was a -0.27% (P<0.001) quarterly slope decrease after policy #1 and a 0.32%
      (P<0.01) slope increase after policy #2 with total decrease attributable to
      policy changes of 127,300 prescriptions per year. For nontarget essential brands,
      there was a level increase of 0.91% (P<0.001) after policy #1 with increased use
      attributable to policy changes of 98,300 prescriptions per year. CONCLUSIONS: Two
      copayment policies designed to encourage use of selected generic medications
      modestly increased their use; however, there was a shift in other essential
      medications from generics to brands, which could increase Medicaid costs. When
      adjusting copayments, careful consideration must be given to unintended
      consequences of specific policy structures.

PMID- 24686393
TI  - microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic
      lymphocytic leukemia.
AB  - A commonly deleted region in chronic lymphocytic leukemia (CLL) is the 11q22-23
      region, which encompasses the ATM gene. Evidence suggests that tumor suppressor
      genes other than ATM are likely to be involved in CLL with del(11q). A microRNA
      (miR) cluster including the miR-34b and miR-34c genes is located, among other
      genes, within the commonly deleted region (CDR) at 11q. Interestingly, these miRs
      are part of the TP53 network and have been shown to be epigenetically regulated.
      In this study, we investigated the expression and methylation status of these
      miRs in a well-characterized cohort of CLL, including cases with/without 11q
      deletion. We show that the miR-34b/c promoter was aberrantly hypermethylated in a
      large proportion of CLL cases (48%, 25/52 cases). miR-34b/c expression correlated
      inversely to DNA methylation (P = 0.003), and presence of high H3K37me3 further
      suppressed expression regardless of methylation status. Furthermore, increased
      miR-34b/c methylation inversely correlated with the presence of 11q-deletion,
      indicating that methylation and del(11q) independently silence these miRs.
      Finally, 5-azacytidine and trichostatin A exposure synergistically increased the
      expression of miR-34b/c in CLL cells, and transfection of miR-34b or miR-34c into
      HG3 CLL cells significantly increased apoptosis. Altogether, our novel data
      suggest that miR-34b/c is a candidate tumor suppressor that is epigenetically
      silenced in CLL. 

PMID- 24686395
TI  - Specific adsorption of perchlorate anions on Pt{hkl} single crystal electrodes.
AB  - The voltammetry of Pt{111}, Pt{100}, Pt{110} and Pt{311} single crystal
      electrodes as a function of perchloric acid concentration (0.05-2.00 M) has been
      studied in order to test the assertion made in recent reports by Watanabe et al.
      that perchlorate anions specifically adsorb on polycrystalline platinum. Such an
      assertion would have significant ramifications for our understanding of
      electrocatalytic processes at platinum surfaces since perchlorate anions at low
      pH have classically been assumed not to specifically adsorb. For Pt{111}, it is
      found that OHad and electrochemical oxide states are both perturbed significantly
      as perchloric acid concentration is increased. We suggest that this is due to
      specific adsorption of perchlorate anions competing with OHad for adsorption
      sites. The hydrogen underpotential deposition (H UPD) region of Pt{111} however
      remains unchanged although evidence for perchlorate anion decomposition to
      chloride on Pt{111} is reported. In contrast, for Pt{100} no variation in the
      onset of electrochemical oxide formation is found nor any shift in the potential
      of the OHad state which normally results from the action of specifically
      adsorbing anions. This suggests that perchlorate anions are non-specifically
      adsorbed on this plane although strong changes in all H UPD states are observed
      as perchloric acid concentration is increased. This manifests itself as a
      redistribution of charge from the H UPD state situated at more positive potential
      to the one at more negative potential. For Pt{110} and Pt{311}, marginal changes
      in the onset of electrochemical oxide formation are recorded, associated with
      specific adsorption of perchlorate. Specific adsorption of perchlorate anions on
      Pt{111} is deleterious to electrocatalytic activity in relation to the oxygen
      reduction reaction (ORR) as measured using a rotating disc electrode (RDE) in a
      hanging meniscus configuration. This study supports previous work suggesting that
      a large component of the ORR activity on platinum is governed by simple site
      blocking by specifically adsorbed anions and/or electrosorbed oxide. 

PMID- 24686396
TI  - Lister's relationship with patients: 'A successful case'
AB  - An important aspect of Joseph Lister's work that has received relatively little
      attention is his relationship with patients. However, a manuscript written by one
      of his patients, Margaret Mathewson's 'A Sketch of Eight Months a patient, in the
      Royal Infirmary of Edinburgh, A.D. 1877', provides detail about the surgeon as
      seen 'from below'-that is, by a charity patient. Although excerpts from
      Mathewson's 'Sketch' have previously been published, an earlier version of the
      'Sketch' has only recently been identified as such. That earlier version
      represents Lister not only as actively concerned with patient education, but also
      as strongly supportive of patients' rights, encouraging ward patients to report
      maltreatment at the hands of the staff.

PMID- 24686398
TI  - Glassiness and exotic entropy scaling induced by quantum fluctuations in a
      disorder-free frustrated magnet.
AB  - When spins are arranged in a lattice of triangular motif, the phenomenon of
      frustration leads to numerous energetically equivalent ground states, and results
      in exotic states such as spin liquid and spin ice. Here we report an alternative
      situation: a system, classically a liquid, freezes in the clean limit into a
      glassy state induced by quantum fluctuations. We call such glassy state a spin
      jam. The case in point is a frustrated magnet, where spins are arranged in a
      triangular network of bipyramids. Quantum corrections break the classical
      degeneracy into a set of aperiodic spin configurations forming local minima in a
      rugged energy landscape. This is established by mapping the problem into tiling
      with hexagonal tiles. The number of tessellations scales with the boundary length
      rather than its volume, showing the absence of local zero-energy modes. Low
      temperature thermodynamics is discussed to compare it with other glassy
      materials. 

PMID- 24686397
TI  - Drosophila Mcm10 is required for DNA replication and differentiation in the
      compound eye.
AB  - Mini chromosome maintenance 10 (Mcm10) is an essential protein, which is
      conserved from S. cerevisiae to Drosophila and human, and is required for the
      initiation of DNA replication. Knockdown of Drosophila Mcm10 (dMcm10) by RNA
      interference in eye imaginal discs induces abnormal eye morphology (rough eye
      phenotype), and the number of ommatidia is decreased in adult eyes. We also
      observed a delay in the S phase and M phase in eye discs of dMcm10 knockdown fly
      lines. These results show important roles for dMcm10 in the progression of S and
      M phases. Furthermore, genome damage and apoptosis were induced by dMcm10
      knockdown in eye imaginal discs. Surprisingly, when we used deadpan-lacZ and
      klingon-lacZ enhancer trap lines to monitor the photoreceptor cells in eye discs,
      knockdown of dMcm10 by the GMR-GAL4 driver reduced the signals of R7
      photoreceptor cells. These data suggest an involvement of dMcm10 in R7 cell
      differentiation. This involvement appears to be independent of the apoptosis
      induced by dMcm10 knockdown. Together, these results suggest that dMcm10
      knockdown has an effect on DNA replication and R7 cell differentiation. 

PMID- 24686399
TI  - Current and future applications of the intra-aortic balloon pump.
AB  - PURPOSE OF REVIEW: The intra-aortic balloon pump (IABP) has been used for more
      than 40 years. Although recommended in a wide variety of clinical settings, most
      of these indications are not evidence-based. This review focuses on studies
      challenging these traditional indications and evaluates potentially new
      applications of intra-aortic counterpulsation. RECENT FINDINGS: Recent studies
      have failed to confirm an improvement in clinical outcomes conferred by the IABP
      in patients developing cardiogenic shock after acute myocardial infarction. This
      issue is in need of further investigations. While conflicting results of several
      retrospective studies and meta-analyses have been published regarding the
      performance of the IABP in high-risk percutaneous coronary interventions, it has
      recently been found to improve the long-term clinical outcomes of patients in
      whom it was implanted before the procedure. Small, single-center studies have
      reported the use of the IABP as a bridge to transplantation or candidacy for left
      ventricular assist device implantation. The recently reported feasibility and
      safety of its insertion via the subclavian or axillary arteries will facilitate
      these applications. SUMMARY: The revisiting of available data and the performance
      of new, thoughtfully designed trials should clarify the proper indications for
      the IABP.

PMID- 24686400
TI  - Pharmacologic therapies for acute cardiogenic shock.
AB  - PURPOSE OF REVIEW: The natural history of cardiogenic shock has improved
      significantly with the utilization of revascularization and mechanical
      circulatory support. Despite the interest in identifying new pharmacological
      agents, the medical therapy to restore perfusion is limited by their side-effects
      and no solid evidence about improving outcomes. In this article, we review the
      current pharmacological agents utilized during cardiogenic shock. RECENT
      FINDINGS: Inotropes and vasopressors are widely used to improve hemodynamics
      acutely; however, reliable information regarding comparative efficacy of
      individual agents is lacking. A subanalysis of a prospective randomized trial
      suggested that norepinephrine may be preferred over dopamine in patients with
      cardiogenic shock. Levosimendan is a new inotrope with calcium sensitization
      properties that improves acute hemodynamics, but with uncertain effects in
      mortality. Diuretics are used to decongest patients; however, mortality data are
      not available. Inhibition of inflammation during cardiogenic shock seems to be a
      potential therapeutic target; however, initial clinical studies in this area have
      not shown benefit. SUMMARY: The current pharmacological treatment for cardiogenic
      shock includes inotropes, vasopressors and diuretics. The information about
      comparative effective outcomes is limited and their use should be limited as a
      temporary measure as a bridge to recovery, mechanical circulatory support or
      heart transplantation.

PMID- 24686401
TI  - Emergent use of mechanical circulatory support devices: ethical dilemmas.
AB  - PURPOSE OF REVIEW: Mechanical Circulatory Support (MCS) devices are 'life
      sustaining devices' placed as a bridge to decision, either recovery,
      transplantation or a lifetime tether with the device. Cardiogenic shock may
      compromise patient autonomy, or the right for an individual patient to determine
      his own care. This review addresses an ethical dilemma in the context of complex
      clinical medical decision-making, during marked uncertainty for outcomes. RECENT
      FINDINGS: The language in an advanced directive is often imprecise and may not
      provide clear guidance, especially for emergent decisions related to MCS devices.
      Despite improving outcomes, application of MCS in critical illness is associated
      with excessive morbidity and quality of life-limiting adverse outcomes. Several
      cohort experiences now exist that define deactivation of Left Ventricular Assist
      Devices (LVADs) in futility as now deemed as morally and ethically appropriate.
      In contradistinction to euthanasia, deactivation of an LVAD does not introduce
      new intervention or an additional surgical injury, thereby allowing the patient
      to die from their original disorder. SUMMARY: Clinicians must maintain the
      principle of patient autonomy, ensure the viability of an appropriate informed
      consent process and facilitate surrogate judgment. An interdisciplinary team
      based approach is required, and, in some cases, assisted by formal ethics
      consultations in vexing situations.

PMID- 24686402
TI  - Spotlight on cardiogenic shock therapies in the era of mechanical circulatory
      support.

PMID- 24686403
TI  - Identification of genes differentially expressed between resistant and
      susceptible tomato lines during time-course interactions with Xanthomonas
      perforans race T3.
AB  - Bacterial spot caused by several Xanthomonas sp. is one of the most devastating
      diseases in tomato (Solanum lycopersicum L.). The genetics of hypersensitive
      resistance to X. perforans race T3 has been intensively investigated and
      regulatory genes during the infection of race T3 have been identified through
      transcriptional profiling. However, no work on isolating regulatory genes for
      field resistance has been reported. In this study, cDNA-amplified fragment length
      polymorphism technique was used to identify differentially expressed transcripts
      between resistant tomato accession PI 114490 and susceptible variety OH 88119 at
      3, 4 and 5 days post-inoculation of the pathogen. Using 256 selective primer
      combinations, a total of 79 differentially expressed transcript-derived fragments
      (TDFs) representing 71 genes were obtained. Of which, 60 were up-regulated and 4
      were down-regulated in both tomato lines, 4 were uniquely up-regulated and 2 were
      uniquely down-regulated in PI 114490, and 1 was specifically up-regulated in OH
      88119. The expression patterns of 19 representative TDFs were further confirmed
      by semi-quantitative and/or quantitative real time RT-PCR. These results
      suggested that the two tomato lines activated partly similar defensive mechanism
      in response to race T3 infection. The data obtained here will provide some
      fundamental information for elucidating the molecular mechanism of response to
      race T3 infection in tomato plants with field resistance. 

PMID- 24686404
TI  - Validity of self-reported versus hospital-coded diagnosis of stroke: a cross
      sectional and longitudinal study.
AB  - BACKGROUND: Population-based studies, as well as clinicians, often rely on self
      report and hospital records to obtain a history of stroke. This study aimed to
      compare the validity of the diagnosis of stroke by self-report and by hospital
      coding according to their cross-sectional association with prevalent vascular
      risk factors, and longitudinal association with recurrent stroke and major
      cardiovascular outcomes in a large cohort of older Australian men. METHODS:
      Between 1996 and 1999, 11,745 older men were surveyed for a self-reported history
      of stroke as part of the Health in Men Study (HIMS). Previous hospitalization for
      stroke was obtained with consent from linked medical records via the Western
      Australian Data Linkage System (WADLS). Subjects were followed by WADLS until
      December 31, 2010, for hospitalization for stroke, cardiovascular events, and all
      cause mortality. The primary outcome was hospitalisation for stroke during follow
      up. Secondary outcomes included incident vascular events and composite vascular
      endpoints. RESULTS: At baseline, a history of stroke was reported by 903 men
      (7.7%), previous hospitalisation for stroke was recorded in 717 (6.1%), both self
      report and hospitalisation in 467 (4.0%), and no history of stroke in 10,696 men
      (91.1%). Prevalent cardiovascular disease and peripheral arterial disease were
      more common among men with previous hospitalisation for stroke than a history of
      self-reported stroke (p < 0.001). In longitudinal analyses, incident aortic
      aneurysm was also more common among men with baseline history of hospitalization
      for stroke (adjusted hazard ratio (HR) 1.71, 95% CI 1.12-2.60) than among men
      with self-reported stroke (HR 0.88, 95% CI 0.56-1.36) compared to men with no
      history of stroke. With regard to the primary outcome, the rate of
      hospitalisation for stroke during follow-up was significantly higher among men
      with self-reported stroke (HR 2.44, 95% CI 2.03-2.94), hospital-coded stroke
      (adjusted HR 3.02, 2.42-3.78) and both self-reported and hospital-coded stroke
      (adjusted HR 3.33, 2.82-3.92) compared to participants with no previous stroke.
      Time to recurrent stroke was similar among different methods of initial stroke
      diagnosis (p = 0.067). CONCLUSIONS: Self-reported stroke and hospital-coded
      stroke have a similar prognostic value for predicting the risk of recurrent
      stroke. This supports the use of these ways of assessing a history of stroke for
      the clinical purposes of secondary prevention and for further epidemiological
      studies.

PMID- 24686405
TI  - The type, but not the amount, of information available influences toddlers' fast
      mapping and retention of new words.
AB  - PURPOSE: The authors of this study examined whether the type and number of word
      learning cues affect how children infer and retain word-meaning mappings and
      whether the use of these cues changes with age. METHOD: Forty-eight 18- to 36
      month-old children with typical language participated in a fast-mapping task in
      which 6 novel words were presented with 3 types of cues to the words' referents,
      either singly or in pairs. One day later, children were tested for retention of
      the novel words. RESULTS: By 24 months of age, children correctly inferred the
      referents of the novel words at a significant level. Children retained the
      meanings of words at a significant rate by 30 months of age. Children retained
      the first 3 of the 6 word-meaning mappings by 24 months of age. For both fast
      mapping and retention, the efficacy of different cue types changed with
      development, but children were equally successful whether the novel words were
      presented with 1 or 2 cues. CONCLUSION: The type of information available to
      children at fast mapping affects their ability to both form and retain word
      meaning associations. Providing children with more information in the form of
      paired cues had no effect on either fast mapping or retention.

PMID- 24686406
TI  - School-based influenza vaccination: parents' perspectives.
AB  - BACKGROUND: School-age children are important drivers of annual influenza
      epidemics yet influenza vaccination coverage of this population is low despite
      universal publicly funded influenza vaccination in Alberta, Canada. Immunizing
      children at school may potentially increase vaccine uptake. As parents are a key
      stakeholder group for such a program, it is important to consider their concerns.
      PURPOSE: We explored parents' perspectives on the acceptability of adding an
      annual influenza immunization to the immunization program that is currently
      delivered in Alberta schools, and obtained suggestions for structuring such a
      program. PARTICIPANTS: Forty-eight parents of children aged 5-18 years
      participated in 9 focus groups. Participants lived in urban areas of the Alberta
      Health Services Calgary Zone. FINDINGS: Three major themes emerged: Advantages of
      school-based influenza vaccination (SBIV), Disadvantages of SBIV, and
      Implications for program design & delivery. Advantages were perceived to occur
      for different populations: children (e.g. emotional support), families (e.g.
      convenience), the community (e.g. benefits for school and multicultural
      communities), the health sector (e.g. reductions in costs due to burden of
      illness) and to society at large (e.g. indirect conduit of information about
      health services, building structure for pandemic preparedness, building healthy
      lifestyles). Disadvantages, however, might also occur for children (e.g. older
      children less likely to be immunized), families (e.g. communication challenges,
      perceived loss of parental control over information, choices and decisions) and
      the education sector (loss of instructional time). Nine second-level themes
      emerged within the major theme of Implications for program design & delivery:
      program goals/objectives, consent process, stakeholder consultation, age
      appropriate program, education, communication, logistics, immunizing agent, and
      clinic process. CONCLUSIONS: Parents perceived advantages and disadvantages to
      delivering annual seasonal influenza immunizations to children at school. Their
      input gives a framework of issues to address in order to construct robust,
      acceptable programs for delivering influenza or other vaccines in schools.

PMID- 24686407
TI  - Long-term effects of early adolescent methamphetamine exposure on depression-like
      behavior and the hypothalamic vasopressin system in mice.
AB  - Methamphetamine (MA) has neurotoxic effects on the adult human brain that can
      lead to deficits in behavior and cognition. However, relatively little research
      has examined the behavioral or neurotoxic effects of MA in adolescents. The
      rising rates of adolescent MA use make it imperative that we understand the long
      term effects of MA exposure on the adolescent brain and how these effects may
      differ from those seen in adults. In this study, the long-term effects of MA
      exposure during early adolescence on behavior and the vasopressin system in the
      paraventricular nucleus of the hypothalamus in late adolescent and adult male and
      female C57BL/6J mice were examined. MA exposure increased depression-like
      behavior in the Porsolt forced swim test in both late adolescent and adult male
      and female mice. Late adolescent male mice exposed to MA also showed a decrease
      in the number of vasopressin-immunoreactive neurons in the paraventricular
      nucleus compared to sex-matched saline-treated controls. Thus, similar to humans
      exposed to MA during adolescence, mice exposed to MA during adolescence show
      increased depression-like behavior later in life. These changes in behavior may
      be related to MA-induced alterations in vasopressin and the hypothalamic
      pituitary-adrenal axis, especially in males.

PMID- 24686408
TI  - Revealing the hidden language of complex networks.
AB  - Sophisticated methods for analysing complex networks promise to be of great
      benefit to almost all scientific disciplines, yet they elude us. In this work, we
      make fundamental methodological advances to rectify this. We discover that the
      interaction between a small number of roles, played by nodes in a network, can
      characterize a network's structure and also provide a clear real-world
      interpretation. Given this insight, we develop a framework for analysing and
      comparing networks, which outperforms all existing ones. We demonstrate its
      strength by uncovering novel relationships between seemingly unrelated networks,
      such as Facebook, metabolic, and protein structure networks. We also use it to
      track the dynamics of the world trade network, showing that a country's role of a
      broker between non-trading countries indicates economic prosperity, whereas
      peripheral roles are associated with poverty. This result, though intuitive, has
      escaped all existing frameworks. Finally, our approach translates network
      topology into everyday language, bringing network analysis closer to domain
      scientists. 

PMID- 24686409
TI  - Hybridizing conversational and clear speech to investigate the source of
      increased intelligibility in speakers with Parkinson's disease.
AB  - PURPOSE: A speech analysis-resynthesis paradigm was used to investigate segmental
      and suprasegmental acoustic variables explaining intelligibility variation for 2
      speakers with Parkinson's disease (PD). METHOD: Sentences were read in
      conversational and clear styles. Acoustic characteristics from clear sentences
      were extracted and applied to conversational sentences, yielding 6 hybridized
      versions of sentences in which segment durations, short-term spectrum, energy
      characteristics, or fundamental frequency characteristics for clear productions
      were applied individually or in combination to conversational productions.
      Listeners (N = 20) judged intelligibility in transcription and scaling tasks.
      RESULTS: Intelligibility increases above conversation were more robust for
      transcription, but the pattern of intelligibility improvement was similar across
      tasks. For 1 speaker, hybridization involving only clear energy characteristics
      yielded an 8.7% improvement in transcription intelligibility above conversation.
      For the other speaker, hybridization involving clear spectrum yielded an 18%
      intelligibility improvement, whereas hybridization involving both clear spectrum
      and duration yielded a 13.4% improvement. CONCLUSIONS: Not all production changes
      accompanying clear speech explain its improved intelligibility. Suprasegmental
      adjustments contributed to intelligibility improvements when segmental
      adjustments, as inferred from vowel space area, were not robust. Hybridization
      can be used to identify acoustic variables explaining intelligibility variation
      in mild dysarthria secondary to PD.

PMID- 24686410
TI  - Rhythm as a coordinating device: entrainment with disordered speech.
AB  - PURPOSE: The rhythmic entrainment (coordination) of behavior during human
      interaction is a powerful phenomenon, considered essential for successful
      communication, supporting social and emotional connection, and facilitating sense
      making and information exchange. Disruption in entrainment likely occurs in
      conversations involving those with speech and language impairment, but its
      contribution to communication disorders has not been defined. As a first step to
      exploring this phenomenon in clinical populations, the present investigation
      examined the influence of disordered speech on the speech production properties
      of healthy interactants. METHOD: Twenty-nine neurologically healthy interactants
      participated in a quasi-conversational paradigm, in which they read sentences
      (response) in response to hearing prerecorded sentences (exposure) from speakers
      with dysarthria (n = 4) and healthy controls (n = 4). Recordings of read
      sentences prior to the task were also collected (habitual). RESULTS: Findings
      revealed that interactants modified their speaking rate and pitch variation to
      align more closely with the disordered speech. Production shifts in these
      rhythmic properties, however, remained significantly different from corresponding
      properties in dysarthric speech. CONCLUSION: Entrainment offers a new avenue for
      exploring speech and language impairment, addressing a communication process not
      currently explained by existing frameworks. This article offers direction for
      advancing this line of inquiry.

PMID- 24686411
TI  - Structural biology: solving the T4SS structural mystery.

PMID- 24686412
TI  - Techniques and applications: RNAi 'off-targets' pathogen infection.

PMID- 24686413
TI  - Semi-synthetic artemisinin: a model for the use of synthetic biology in
      pharmaceutical development.
AB  - Recent developments in synthetic biology, combined with continued progress in
      systems biology and metabolic engineering, have enabled the engineering of
      microorganisms to produce heterologous molecules in a manner that was previously
      unfeasible. The successful synthesis and recent entry of semi-synthetic
      artemisinin into commercial production is the first demonstration of the
      potential of synthetic biology for the development and production of
      pharmaceutical agents. In this Review, we describe the metabolic engineering and
      synthetic biology approaches that were used to develop this important
      antimalarial drug precursor. This not only demonstrates the incredible potential
      of the available technologies but also illuminates how lessons learned from this
      work could be applied to the production of other pharmaceutical agents. 

PMID- 24686415
TI  - Synthetic biology: E. coli reporter gets the inside scoop.

PMID- 24686414
TI  - A brief history of synthetic biology.
AB  - The ability to rationally engineer microorganisms has been a long-envisioned goal
      dating back more than a half-century. With the genomics revolution and rise of
      systems biology in the 1990s came the development of a rigorous engineering
      discipline to create, control and programme cellular behaviour. The resulting
      field, known as synthetic biology, has undergone dramatic growth throughout the
      past decade and is poised to transform biotechnology and medicine. This Timeline
      article charts the technological and cultural lifetime of synthetic biology, with
      an emphasis on key breakthroughs and future challenges.

PMID- 24686416
TI  - Ablation of a single cell from eight-cell embryos of the amphipod crustacean
      Parhyale hawaiensis.
AB  - The amphipod Parhyale hawaiensis is a small crustacean found in intertidal marine
      habitats worldwide. Over the past decade, Parhyale has emerged as a promising
      model organism for laboratory studies of development, providing a useful outgroup
      comparison to the well studied arthropod model organism Drosophila melanogaster.
      In contrast to the syncytial cleavages of Drosophila, the early cleavages of
      Parhyale are holoblastic. Fate mapping using tracer dyes injected into early
      blastomeres have shown that all three germ layers and the germ line are
      established by the eight-cell stage. At this stage, three blastomeres are fated
      to give rise to the ectoderm, three are fated to give rise to the mesoderm, and
      the remaining two blastomeres are the precursors of the endoderm and germ line
      respectively. However, blastomere ablation experiments have shown that Parhyale
      embryos also possess significant regulatory capabilities, such that the fates of
      blastomeres ablated at the eight-cell stage can be taken over by the descendants
      of some of the remaining blastomeres. Blastomere ablation has previously been
      described by one of two methods: injection and subsequent activation of
      phototoxic dyes or manual ablation. However, photoablation kills blastomeres but
      does not remove the dead cell body from the embryo. Complete physical removal of
      specific blastomeres may therefore be a preferred method of ablation for some
      applications. Here we present a protocol for manual removal of single blastomeres
      from the eight-cell stage of Parhyale embryos, illustrating the instruments and
      manual procedures necessary for complete removal of the cell body while keeping
      the remaining blastomeres alive and intact. This protocol can be applied to any
      Parhyale cell at the eight-cell stage, or to blastomeres of other early cleavage
      stages. In addition, in principle this protocol could be applicable to early
      cleavage stage embryos of other holoblastically cleaving marine invertebrates. 

PMID- 24686418
TI  - A flow adhesion assay to study leucocyte recruitment to human hepatic sinusoidal
      endothelium under conditions of shear stress.
AB  - Leucocyte infiltration into human liver tissue is a common process in all adult
      inflammatory liver diseases. Chronic infiltration can drive the development of
      fibrosis and progression to cirrhosis. Understanding the molecular mechanisms
      that mediate leucocyte recruitment to the liver could identify important
      therapeutic targets for liver disease. The key interaction during leucocyte
      recruitment is that of inflammatory cells with endothelium under conditions of
      shear stress. Recruitment to the liver occurs within the low shear channels of
      the hepatic sinusoids which are lined by hepatic sinusoidal endothelial cells
      (HSEC). The conditions within the hepatic sinusoids can be recapitulated by
      perfusing leucocytes through channels lined by human HSEC monolayers at specific
      flow rates. In these conditions leucocytes undergo a brief tethering step
      followed by activation and firm adhesion, followed by a crawling step and
      subsequent transmigration across the endothelial layer. Using phase contrast
      microscopy, each step of this 'adhesion cascade' can be visualized and recorded
      followed by offline analysis. Endothelial cells or leucocytes can be pretreated
      with inhibitors to determine the role of specific molecules during this process. 

PMID- 24686419
TI  - Animal-type malignant melanoma associated with nevus of Ota in the orbit of a
      Japanese woman: a case report.
AB  - We present a patient with an animal-type malignant melanoma associated with the
      nevus of Ota in the orbit who showed a good prognosis after a combination of
      orbital extirpation, chemotherapy, stereotactic radiotherapy, and gamma knife. A
      42-year-old Japanese woman presented with two tumors, one pathologically
      diagnosed as right-sided intraconal animal-type malignant melanoma and the other
      intracranially, presumed to be of the same pathogenesis and both were considered
      to have arisen from the nevus of Ota. She underwent an extirpation of the orbit,
      chemotherapy (DAV therapy, which is a combination of dacarbazine, nimustine, and
      vincristine), stereotactic radiotherapy (54 Gy in 27 fractions), and gamma knife
      (marginal dose was 17 Gy, target volume was 0.2 ml). She has been alive for 33
      months since the extirpation, with no sign of local recurrence, new metastasis,
      nor enlargement of the intracranial tumor. Not just combination therapy but also
      the low malignancy of animal-type melanoma may have contributed toward the good
      prognosis. 

PMID- 24686420
TI  - The transcription factor CUTL1 is associated with proliferation and prognosis in
      malignant melanoma.
AB  - The transcription factor CUTL1 (CCAAT displacement protein 1) has been reported
      to participate in the proliferation of diverse types of cancer. In the present
      study, we investigated the potential involvement of CUTL1 in the proliferation of
      malignant melanoma. We found that CUTL1 expression was upregulated in malignant
      melanoma tissues and cell lines, and CUTL1 expression was selected as a
      prognostic predictor for malignant melanoma patients by both univariate and
      multivariate analysis. Knockdown of CUTL1 by short hairpin RNA significantly
      reduced the colony-forming ability of malignant melanoma cells in vitro and
      reduced tumor growth in vivo, whereas forced overexpression of CUTL1 produced the
      opposite results. Consistently, cell cycle progression was impaired upon
      downregulation of CUTL1 and enhanced when CUTL1 was upregulated. Additional
      experiments suggested that CUTL1 may regulate the proliferation of malignant
      melanoma by modulating the expression of cell cycle-related proteins. 

PMID- 24686421
TI  - Convergence of hypoxia and TGFbeta pathways on cell cycle regulation in human
      hematopoietic stem/progenitor cells.
AB  - Although it has been shown that HIF1 and 2 fulfill essential roles within the
      hematopoietic system and in the regulation of HSC fate, little is currently known
      about the specific mechanisms that are involved. We identified transcriptome
      changes induced by hypoxia, constitutively active HIF1(P402/564) and
      HIF2(P405/531) in human cord blood CD34+ cells. Thus, we were able to identify
      common hypoxia-HIF1-HIF2 gene signatures, but we also identified specific target
      genes that were exclusively regulated by HIF1, HIF2 or hypoxia. Geneset
      enrichment analysis (GSEA) revealed that, besides known pathways associated with
      "hypoxia-induced signaling", also significant enrichment for the Transforming
      Growth Factor beta (TGFbeta) pathway was observed within the hypoxia/HIF1/HIF2
      transcriptomes. One of the most significantly upregulated genes in both gene sets
      was the cyclin dependent kinase inhibitor CDKN1C (p57kip2). Combined hypoxia
      treatment or HIF overexpression together with TGFbeta stimulation resulted in
      enhanced expression of CDKN1C and enhanced cell cycle arrest within the
      CD34+/CD38- stem cell compartment. Interestingly, we observed that CD34+ cells
      cultured under hypoxic conditions secreted high levels of latent TGFbeta,
      suggesting an auto- or paracrine role of TGFbeta in the regulation of quiescence
      of these cells. However, knockdown of SMAD4 could not rescue the hypoxia induced
      cell cycle arrest, arguing against direct effects of hypoxia-induced secreted
      TGFbeta. Finally, the Galpha-coupled receptor GTPase RGS1 was identified as a HIF
      dependent hypoxia target that dampens SDF1-induced migration and signal
      transduction in human CD34+ stem/progenitor cells. 

PMID- 24686425
TI  - Polyomavirus BK viremia in kidney transplant recipients after desensitization
      with IVIG and rituximab.
AB  - BACKGROUND: Desensitization with intravenous immune globulin (IVIG) and rituximab
      improves transplantation rates. It is unclear if desensitization increases the
      risk of polyomavirus BK (BKV) viremia. Here, BKV viremia in HLA-sensitized
      patients after desensitization with IVIG and rituximab was analyzed. METHODS:
      Baseline characteristics and outcomes were compared in the desensitized group
      (N=187) and the non-desensitized group (N=284). Surveillance for BKV viremia was
      done at 1, 2, 3, 6, 9, and 12 months posttransplant. Univariable and
      multivariable analyses were performed. RESULTS: BKV viremia was observed in 20%
      of the desensitized and 10% of the non-desensitized (P<0.001) groups by 2 years
      posttransplant. The desensitized group had more lymphocyte depleting induction
      and more rejection. They also had a greater degree of viremia with more patients
      having a peak viral load greater than 10,000 copies per milliliter (P<0.001).
      However, there was no significant difference in BKV-associated nephropathy or
      graft loss in the two groups. There was an association of BKV viremia with
      desensitization and lymphocyte induction. Only desensitization remained a
      significant predictor in the multivariable model with an adjusted HR of 2.13 (95%
      CI 1.21-3.77, P=0.009). CONCLUSIONS: Desensitization with IVIG and rituximab is
      associated with a higher incidence of BKV viremia with high viral copies and was
      the major predictor of BKV viremia in the multivariable model. More frequent
      surveillance for BKV viremia and an early, aggressive treatment strategy are
      essential for preventing high BKV viral loads in this patient population.

PMID- 24686422
TI  - [Epidemiology and prognosis of childhood cancers at Gabriel-Toure Teaching
      Hospital (Bamako, Mali)].
AB  - Cancer today is being treated as a public health problem in Africa, as in
      developed countries. OBJECTIVE: The aim of this retrospective study was to
      evaluate the epidemiology and outcome of children treated in the Pediatric
      Oncology Unit of Gabriel Toure Teaching Hospital in Bamako (Mali), six years
      after it opened. METHODS: Retrospective study of the files of all children aged
      15 and younger diagnosed with cancer and treated by chemotherapy between January
      1, 2005, and December 31, 2010. RESULTS: The study included 690 children. Their
      mean age was 24 months. The time from observation of first symptoms to
      consultation was less than 3 months in 200 cases (29%), from 3 to 10 months in
      256 (37.1%), and more than 10 months in 234 (33.9%). The five most common
      childhood cancers were malignant non-Hodgkin's lymphoma (NHL) (n=231, 33.5%),
      retinoblastoma (n=170, 24.6%), nephroblastoma (n=102, 14.8%), acute lymphoblastic
      leukemia (n=54, 7%), and Hodgkin's disease (n=34, 4%). Six years after the unit
      opened and after a mean follow-up of 3 years, we recorded 272 deaths (39.4%); at
      least 238 children are still alive (34.5%), with 180 cases (26.1%) lost to follow
      up. CONCLUSION: Childhood cancer survival is still low in Mali, and the rate of
      loss to follow-up quite high.

PMID- 24686426
TI  - Lower variability in 24-hour exposure during once-daily compared to twice-daily
      tacrolimus formulation in kidney transplantation.
AB  - INTRODUCTION: Tacrolimus has originally been registered as a twice-daily
      formulation (Prograf, Tac BID), although a once-daily formulation (Advagraf, Tac
      QD) is also available. A reduced intrapatient variability of Tac Cmin, a
      surrogate marker for 24-hour drug exposure (AUC0-24), has been suggested. The
      variability of AUC0-24 has never been studied prospectively yet. The purpose of
      this study was to investigate the change in intrapatient variability of Tac AUC0
      24 after converting from Tac BID to Tac QD. METHODS: Forty renal transplant
      patients on Tac BID were converted on a 1:1 (mg/mg) basis to Tac QD in an
      investigator-driven comparative pharmacokinetic (PK) study. AUC0-24 was
      determined five times before and after conversion. Duplicate samples were
      collected by the patients themselves using the dried blood spot method. The main
      outcome measure is the change in intrapatient variability of AUC0-24 expressed as
      coefficient of variation (CV). Moreover, the influence of Cyp3A5 genotype
      polymorphism on the change in CV was studied. RESULTS: In total, 400 AUC0-24
      profiles were available for analysis. Conversion to Tac QD resulted in a
      significant improvement in intra-patient CV from 14.1% to 10.9% (P=0.012).
      Patients with the Cyp3A5*1/*3 genotype (n=11) had a numerically larger
      improvement in CV than patients with the CYP3A5*3/*3 genotype. CONCLUSION:
      Intrapatient CV of Tac AUC0-24 improved after converting from Tac BID to Tac QD
      in stable renal transplant patients, especially in patients with the CYP3A5*1/3
      genotype. Given the very strict protocol of this PK study, this improvement is
      most likely due to the different intrinsic PK properties of Tac QD and Tac BID.

PMID- 24686428
TI  - May-Thurner syndrome complicating left-sided donor nephrectomy.

PMID- 24686427
TI  - Podocyte foot process effacement in postreperfusion allograft biopsies.

PMID- 24686429
TI  - Successful treatment of hemorrhagic cystitis after HLA-mismatched allogeneic
      hematopoietic stem cell transplantation by hyperbaric oxygen.

PMID- 24686430
TI  - Kidney transplantation from a deceased donor with metachromatic leukodystrophy.

PMID- 24686431
TI  - From mourning to scientific legacy: commemorating Lister in London and Scotland.
AB  - This paper examines the changing methods, underlying motives, clienteles and
      controversy surrounding posthumous commemorations of Lord Lister in Britain. The
      importance of the commemorations for professional identity formation continues
      throughout the twentieth century, but World War I appears as a turning point. The
      constituencies commemorating Lister change from broadly international, national
      and civic with an emphasis on fundraising, to more narrowly professional; the use
      of religious imagery is notable after the war in the debates in the 1920s; and as
      his students, so central to the creation and preservation of his image, die, the
      focus begins to shift from the man and his achievements, 'the great benefactor of
      mankind', to his legacy in the current state of subjects related to his work. The
      changing nature of the commemorations suggests that although Lister's precise
      position in the history of surgery is contentious today, his importance as an
      iconic figure in the history of the medical profession is secure.

PMID- 24686432
TI  - Reading comprehension in Parkinson's disease.
AB  - PURPOSE: Although individuals with Parkinson's disease (PD) self-report reading
      problems and experience difficulties in cognitive-linguistic functions that
      support discourse-level reading, prior research has primarily focused on sentence
      level processing and auditory comprehension. Accordingly, the authors
      investigated the presence and nature of reading comprehension in PD,
      hypothesizing that (a) individuals with PD would display impaired accuracy and/or
      speed on reading comprehension tests and (b) reading performances would be
      correlated with cognitive test results. METHOD: Eleven adults with PD and 9 age-
      and education-matched control participants completed tests that evaluated reading
      comprehension; general language and cognitive abilities; and aspects of
      attention, memory, and executive functioning. RESULT: The PD group obtained
      significantly lower scores on several, but not all, reading comprehension,
      language, and cognitive measures. Memory, language, and disease severity were
      significantly correlated with reading comprehension for the PD group. CONCLUSION:
      Individuals in the early stages of PD without dementia or broad cognitive
      deficits can display reading comprehension difficulties, particularly for high-
      versus basic-level reading tasks. These reading difficulties are most closely
      related to memory, high-level language, and PD symptom severity status. The
      findings warrant additional research to delineate further the types and nature of
      reading comprehension impairments experienced by individuals with PD.

PMID- 24686433
TI  - Recall processes for biliary cytology in primary sclerosing cholangitis.
AB  - PURPOSE OF REVIEW: Patients with primary sclerosing cholangitis (PSC) are at an
      increased risk for cholangiocarcinoma (CCA). Distinguishing benign from malignant
      biliary strictures with routine biliary cytology in this population is
      challenging. In this review, we examine the strengths and limitations of biliary
      cytology, review the application of other techniques to help minimize these
      limitations and present a pragmatic approach to address biliary cytology findings
      when encountered in PSC. RECENT FINDINGS: Limitations of biliary cytology and
      other diagnostic studies have driven the development of new techniques and
      applications of existing technologies to improve our ability to diagnose CCA in
      PSC. Polysomy when detected on fluorescence in-situ hybridization (FISH) is an
      independent predictor for the development of CCA. The application of imaging
      techniques and serologic testing such as carbohydrate antigen 19-9 may further
      enhance our ability to risk stratify patients. Recent studies suggest that
      proteomics may allow for the identification of novel biomarkers that could
      enhance our ability to detect CCA. SUMMARY: Given the inherent challenge of
      establishing a diagnosis of CCA, providers should apply a multifaceted approach
      that involves biliary cytology, FISH, serologic testing and advanced imaging
      techniques when CCA is suspected in patients with PSC.

PMID- 24686434
TI  - Aspects on gallbladder cancer in 2014.
AB  - PURPOSE OF REVIEW: To discuss some key issues involved in the management of
      gallbladder cancer (GBC). RECENT FINDINGS: The decline in incidence and mortality
      of GBC began decades before the introduction of laparoscopic surgery. In
      consecutive autopsies and in cases in which cholelithiasis was present, the
      incidence of gallbladder carcinoma is 3-4%. A number of genetic alterations have
      been identified in the different stages of GBC and they support the morphological
      evidence of two pathways by which tumors develop. Some of these genetic changes
      are associated with particular risk factors. All management of GBC and all
      comparisons of treatment results from different centers must be based on the
      stages. SUMMARY: Simple cholecystectomy is the adequate treatment for T1a GBC.
      Lymph node excision improved survival in patients with T2 lesions. Radical en
      bloc resection of T2 tumors offers greater benefit over conventional
      cholecystectomy alone in terms of greater long-term survival times. Provided that
      negative surgical margins are secured, hepatectomy and lymph node resection can,
      therefore, be withheld in most cases in the surgical treatment of pT2 GBC. With
      improvements in surgical and anesthetic techniques, aggressive surgery has proven
      to be performed with safety.

PMID- 24686435
TI  - Bile duct strictures after liver transplantation.
AB  - PURPOSE OF REVIEW: Biliary complications account for relevant morbidity and
      mortality after liver transplantation. Advances have taken place in understanding
      their aetiology, in preventive operative techniques, imaging procedures, as well
      as interventional and endoscopic management. However, progress in living
      donation, donation after cardiac death as well as paediatric transplant
      procedures have changed the incidence and causes of biliary complications. This
      review summarizes recent progress in the field, particularly related to biliary
      strictures after liver transplantation. RECENT FINDINGS: Significant findings in
      the period of interest for this review focussed on improvements of endoscopic
      treatment of postliver transplant biliary complications, including novel stenting
      devices, the routine analysis of bacterial and fungal flora, and the use of
      steroids to prevent postendoscopic retrograde cholangiopancreaticography
      pancreatitis. The importance of cytomegalovirus and hepatitis C in the aetiology
      of biliary complications was highlighted. Under certain circumstances, biliary
      complications after liver transplantation of organs secondary to donation after
      cardiac death may be reduced to a level known from liver transplantation after
      brain death. Further evidence was added to support the risk-adapted use of
      biliary drainage during liver transplantation. SUMMARY: The ongoing research in
      the aetiology, prevention, and treatment of biliary strictures after liver
      transplantation highlights the significance of biliary complications for patient
      and graft outcome.

PMID- 24686437
TI  - Benzene...acetylene: a structural investigation of the prototypical CH...pi
      interaction.
AB  - The structure of a prototype CH...pi system, benzene...acetylene, has been
      determined in the gas phase using Fourier-transform microwave spectroscopy. The
      spectrum is consistent with an effective C(6v) structure with an H...pi distance
      of 2.4921(1) A. The HCCH subunit likely tilts by ~5 degrees  from the benzene
      symmetry axis. The dipole moment was determined to be 0.438(11) D from Stark
      effect measurements. The observed intermolecular distance is longer than in
      similar benzene...HX complexes and than the distances observed in the
      benzene...HCCH cocrystal and predicted by many high level ab initio calculations;
      however, the experimentally estimated binding energy of 7.1(7) kJ mol(-1) is
      similar to previously studied benzene...HX complexes. Several additional sets of
      transitions were observed in the rotational spectrum, likely corresponding to
      excited states arising from low energy intermolecular vibrational modes of the
      dimer.

PMID- 24686436
TI  - Hepatopulmonary syndrome.
AB  - PURPOSE OF REVIEW: To discuss the advances in the understanding of the
      pathophysiology of experimental and human hepatopulmonary syndrome (HPS) and in
      the management of HPS, particularly regarding liver transplantation. RECENT
      FINDINGS: Advances have been made in defining the pathophysiology of HPS in
      experimental models as well as in human disease, including the role of endothelin
      1, pulmonary monocytes, and angiogenesis. Additionally, the implications of the
      presence of HPS as it relates to prioritizing patients for liver transplantation
      and posttransplant outcomes will also be reviewed. SUMMARY: Mechanisms of disease
      continue to be defined in HPS, providing potential targets for pharmacologic
      intervention. Outcomes after liver transplantation are also becoming clearer,
      including the management of HPS with severe hypoxemia.

PMID- 24686438
TI  - Simulating the effects of common and specific abilities on test performance: an
      evaluation of factor analysis.
AB  - PURPOSE: Factor analysis is a useful technique to aid in organizing multivariate
      data characterizing speech, language, and auditory abilities. However, knowledge
      of the limitations of factor analysis is essential for proper interpretation of
      results. The present study used simulated test scores to illustrate some
      characteristics of factor analysis. METHOD: Linear models were used to simulate
      test scores that were determined by multiple latent variables. These simulated
      test scores were evaluated with principal components analysis and, in certain
      cases, structural equation modeling. In addition, a subset of simulated
      individuals characterized by poor test performance was examined. RESULTS: The
      number of factors recovered and their identity do not necessarily correspond to
      the structure of the latent variables that generated the test scores. The first
      principal component may represent variance from multiple uncorrelated sources.
      Practices such as correction or control for general cognitive ability may produce
      misleading results. CONCLUSIONS: Inferences from the results of factor analysis
      should be primarily about the structure of test batteries rather than the
      structure of human mental abilities. Researchers and clinicians should consider
      multiple sources of evidence to evaluate hypotheses about the processes
      generating test results.

PMID- 24686439
TI  - Examining the construct validity of the V-RQOL in speakers who use alaryngeal
      voice.
AB  - PURPOSE: The construct validity of the Voice-Related Quality of Life (V-RQOL;
      Hogikyan & Sethuraman, 1999) measure was evaluated in a sample of 109 individuals
      who have undergone total laryngectomy. METHOD: A principal components factor
      analysis was performed on participant responses to the 10-question V-RQOL
      measure. RESULTS: Factor analysis of the V-RQOL in our alaryngeal sample
      confirmed the presence of two factors (physical and social-emotional), which is
      consistent with the identified domains in the current V-RQOL. However, the
      current data indicate that some of the questions proposed by the original authors
      of the V-RQOL (Questions 7 and 9) do not align with their proposed domains in
      this postlaryngectomy sample. CONCLUSION: The results indicate that some V-RQOL
      questions do not align with their proposed domains. Consequently, an alternative
      scoring algorithm may be warranted for alaryngeal populations, and the authors
      make suggestions for this change that are simple and efficient. Based on the
      findings of the present factor analysis, use of this modified scoring procedure
      may serve to increase the sensitivity of the V-RQOL for those who are
      laryngectomized and use alaryngeal methods of voice and speech. Consequently, the
      value and application of the V-RQOL may be expanded in the clinical setting.

PMID- 24686440
TI  - Prenatal, perinatal, and neonatal risk factors for specific language impairment:
      a prospective pregnancy cohort study.
AB  - PURPOSE: Although genetic factors are known to play a causal role in specific
      language impairment (SLI), environmental factors may also be important. This
      study examined whether there are prenatal, perinatal, and neonatal factors that
      are associated with childhood SLI. METHOD: Participants were members of the Raine
      Study, a prospective cohort investigation of pregnant women and their offspring.
      Parent report indicated that 26 children had received a clinical diagnosis of
      SLI. Data from antenatal and birth medical records were compared between the
      children with SLI and typically developing comparison children (N = 1,799).
      RESULTS: There were no statistically significant differences between the SLI and
      comparison groups in the individual prenatal, perinatal, and neonatal factors
      examined. Aggregate risk scores were calculated for each period on the basis of
      factors known to be associated with neurodevelopmental disorder. There were no
      group differences in aggregate risk scores in the prenatal and perinatal periods.
      However, significantly more children in the SLI group (50%) compared with the
      comparison group (27.6%) experienced 2 or more risk factors during the neonatal
      period. CONCLUSION: The vast majority of prenatal, perinatal, and neonatal
      complications do not play a clear causal role in childhood SLI. However, poor
      neonatal health may signify increased risk for SLI.

PMID- 24686441
TI  - Children with differing developmental trajectories of prelinguistic communication
      skills: language and working memory at age 5.
AB  - PURPOSE: In this article, the authors examine the developmental continuity from
      prelinguistic communication to kindergarten age in language and working memory
      capacity. METHOD: Following work outlining 6 groups of children with different
      trajectories of early communication development (ECD; Maatta, Laakso, Tolvanen,
      Ahonen, & Aro, 2012), the authors examined their later development by
      psychometric assessment. Ninety-one children first assessed at ages 12-21 months
      completed a battery of language and working memory tests at age 5;3
      (years;months). RESULTS: Two of the ECD groups previously identified as being at
      risk for language difficulties continued to show weaker performance at follow-up.
      Seventy-nine percent of the children with compromised language skills at follow
      up were identified on the basis of the ECD groups, but the number of false
      positives was high. The 2 at-risk groups also differed significantly from the
      typically developing groups in the measures tapping working memory capacity.
      CONCLUSIONS: In line with the dimensional view of language impairment, the
      accumulation of early delays predicted the amount of later difficulties; however,
      at the individual level, the prediction had rather low specificity. The results
      imply a strong link between language and working memory and call for further
      studies examining the early developmental interaction between language and
      memory.

PMID- 24686442
TI  - The effect of deep brain stimulation on the speech motor system.
AB  - PURPOSE: Chronic deep brain stimulation of the nucleus ventralis intermedius is
      an effective treatment for individuals with medication-resistant essential
      tremor. However, these individuals report that stimulation has a deleterious
      effect on their speech. The present study investigates one important factor
      leading to these effects: the coordination of oral and glottal articulation.
      METHOD: Sixteen native-speaking German adults with essential tremor, between 26
      and 86 years old, with and without chronic deep brain stimulation of the nucleus
      ventralis intermedius and 12 healthy, age-matched subjects were recorded
      performing a fast syllable repetition task (/papapa/, /tatata/, /kakaka/).
      Syllable duration and voicing-to-syllable ratio as well as parameters related
      directly to consonant production, voicing during constriction, and frication
      during constriction were measured. RESULTS: Voicing during constriction was
      greater in subjects with essential tremor than in controls, indicating a
      perseveration of voicing into the voiceless consonant. Stimulation led to fewer
      voiceless intervals (voicing-to-syllable ratio), indicating a reduced degree of
      glottal abduction during the entire syllable cycle. Stimulation also induced
      incomplete oral closures (frication during constriction), indicating imprecise
      oral articulation. CONCLUSION: The detrimental effect of stimulation on the
      speech motor system can be quantified using acoustic measures at the subsyllabic
      level.

PMID- 24686443
TI  - Ratiometric luminescence thermometry based on crystal-field alternation at the
      extremely narrow 5D0 -> 7F2 transition band of europium(III).
AB  - A dinuclear europium(III) complex with a structure of [BP-(Eu(III))2-(ODA)3] (BP
      = 2,2'-bipyridine-6,6'-dicarboxylic acid bis(N-hydroxy-succinimide) ester, ODA =
      diglycolic acid) shows a fully reversible emission spectral change at the
      extremely narrow (5)D0 -> (7)F2 transition band in response to temperature
      changes ranging from 283 K to 333 K.

PMID- 24686445
TI  - PCAF-dependent epigenetic changes promote axonal regeneration in the central
      nervous system.
AB  - Axonal regenerative failure is a major cause of neurological impairment following
      central nervous system (CNS) but not peripheral nervous system (PNS) injury.
      Notably, PNS injury triggers a coordinated regenerative gene expression
      programme. However, the molecular link between retrograde signalling and the
      regulation of this gene expression programme that leads to the differential
      regenerative capacity remains elusive. Here we show through systematic epigenetic
      studies that the histone acetyltransferase p300/CBP-associated factor (PCAF)
      promotes acetylation of histone 3 Lys 9 at the promoters of established key
      regeneration-associated genes following a peripheral but not a central axonal
      injury. Furthermore, we find that extracellular signal-regulated kinase (ERK)
      mediated retrograde signalling is required for PCAF-dependent regenerative gene
      reprogramming. Finally, PCAF is necessary for conditioning-dependent axonal
      regeneration and also singularly promotes regeneration after spinal cord injury.
      Thus, we find a specific epigenetic mechanism that regulates axonal regeneration
      of CNS axons, suggesting novel targets for clinical application. 

PMID- 24686446
TI  - Isolation of cancer stem cells from human prostate cancer samples.
AB  - The cancer stem cell (CSC) model has been considerably revisited over the last
      two decades. During this time CSCs have been identified and directly isolated
      from human tissues and serially propagated in immunodeficient mice, typically
      through antibody labeling of subpopulations of cells and fractionation by flow
      cytometry. However, the unique clinical features of prostate cancer have
      considerably limited the study of prostate CSCs from fresh human tumor samples.
      We recently reported the isolation of prostate CSCs directly from human tissues
      by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells
      are harvested from surgical specimens and mechanically dissociated. A cell
      suspension is generated and labeled with fluorescently conjugated HLAI and
      stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated
      using a flow cytometer. The principal limitation of this protocol is the
      frequently microscopic and multifocal nature of primary cancer in prostatectomy
      specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular
      characterization and functional validation by transplantation in immunodeficient
      mice. 

PMID- 24686448
TI  - Knockout of TRPV6 causes osteopenia in mice by increasing osteoclastic
      differentiation and activity.
AB  - BACKGROUND: Calcium ion (Ca(2+)) signals are required for osteoclast
      differentiation. Previous study showed that transient receptor potential
      vanilloid 5 (TRPV5) is an essential Ca(2+) transporter in osteoclastogenesis and
      bone resorption. TRPV5 and TRPV6 represent two highly homologous members within
      the transient receptor potential (TRP) superfamily. However, the role of TRPV6 in
      bone metabolism is still controversial and little is known about the involvement
      of TRPV6 in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced
      osteoclastogenesis. METHODS: In our study, gene knockout mice, RNA interference,
      western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase
      (TRAP) staining, pit formation assay, histomorphometry and measurement of serum
      parameters were employed to investigate the role of TRPV6 in bone homeostasis,
      osteoclastogenesis and bone resorption. RESULTS: We found that TRPV6 depletion
      results in noticeable destruction of bone microarchitecture in TRPV6 knockout
      mice (TRPV6(-/-)), suggesting that TRPV6 is a critical regulator in bone
      homeostasis. Inactivation of Trpv6 had no effect on osteoblastic bone formation.
      However, quantification of the TRAP staining showed a significantly increased
      osteoclast number and surface area in the metaphyseal area of femurs bone
      sections derived from TRPV6(-/-) mice. In agreement with our observations from
      TRPV6(-/-) mice, TRPV6 depletion in vitro significantly increased osteoclasts
      differentiation and bone resorption activity. CONCLUSION: Based on these results
      above, we can draw conclusions that TRPV6 plays an essential role in bone
      metabolism and is a critical regulator in osteoclasts differentiation and bone
      resorption.

PMID- 24686447
TI  - Upregulation of colonic luminal polyamines produced by intestinal microbiota
      delays senescence in mice.
AB  - Prevention of quality of life (QOL) deterioration is associated with the
      inhibition of geriatric diseases and the regulation of brain function. However,
      no substance is known that prevents the aging of both body and brain. It is known
      that polyamine concentrations in somatic tissues (including the brain) decrease
      with increasing age, and polyamine-rich foods enhance longevity in yeast, worms,
      flies, and mice, and protect flies from age-induced memory impairment. A main
      source of exogenous polyamines is the intestinal lumen, where they are produced
      by intestinal bacteria. We found that arginine intake increased the concentration
      of putrescine in the colon and increased levels of spermidine and spermine in the
      blood. Mice orally administered with arginine in combination with the probiotic
      bifidobacteria LKM512 long-term showed suppressed inflammation, improved
      longevity, and protection from age-induced memory impairment. This study shows
      that intake of arginine and LKM512 may prevent aging-dependent declines in QOL
      via the upregulation of polyamines. 

PMID- 24686449
TI  - Expression of early growth response 1 affects miR-106a/signal transducer and
      activator of transcription 3 regulating cognitive impairment in ovariectomized
      mice.
AB  - OBJECTIVE: This study aims to investigate the effects of early growth response 1
      (Egr1) on miR-106a/signal transducer and activator of transcription 3 (STAT3)
      regulating cognitive impairment in an ovariectomy model. METHODS: Using the
      Morris water maze test, we assessed escape latency and time spent in a quadrant
      among mice at 6, 8, and 12 weeks after ovariectomy and their age-matched controls
      (n = 15 each group). Egr1, miR-106a, and STAT3 messenger RNA expression (n = 7)
      in the hippocampus and cortex of mice at 6, 8, and 12 weeks after ovariectomy was
      detected by quantitative real-time polymerase chain reaction, whereas Egr1,
      phospho-STAT3 (p-STAT3), and STAT3 protein expression (n = 8) was evaluated by
      Western blot analysis. Moreover, alterations in miR-106a and STAT3 expression
      were investigated in neuroblastoma (SH-SY5Y) cells transfected with a human Egr1
      interference fragment (si-Egr1) or an Egr1-overexpressing plasmid (GV141-Egr1),
      respectively. RESULTS: Escape latency was significantly increased and time spent
      in a platform quadrant was reduced in mice at 12 weeks after ovariectomy compared
      with age-matched controls. Egr1 and miR-106a expression was obviously increased
      in the hippocampus and cortex at 12 weeks after ovariectomy, whereas STAT3 levels
      were decreased compared with 12-week controls. After SH-SY5Y cell transfection
      with the si-Egr1 fragment, miR-106a levels decreased and STAT3/p-STAT3 levels
      increased, whereas cotransfection of the miR-106a mimic caused a significant
      decrease in STAT3 levels. MiR-106a messenger RNA expression was significantly
      increased and STAT3/p-STAT3 protein levels were decreased by Egr1 overexpression,
      whereas simultaneous transfection with the miR-106a inhibitor inhibited
      alterations in STAT3 levels. CONCLUSIONS: This study suggests that Egr1 decreases
      STAT3 expression via miR-106a in ovariectomized mice with cognitive impairment,
      indicating that Egr1 represents a potential target for therapeutic intervention
      in postmenopausal cognitive decline.

PMID- 24686450
TI  - Risk of stroke in healthy postmenopausal women during and after hormone therapy:
      a meta-analysis.
AB  - OBJECTIVE: This meta-analysis aims to examine the risk of stroke in healthy
      postmenopausal women during and after hormone therapy (HT). METHODS: Medline, The
      Cochrane Library, EMBASE, and Google Scholar were searched for randomized
      controlled trials involving healthy postmenopausal women who received HT and were
      followed up for at least 3 years after starting treatment. The primary outcome
      measures were stroke hazard ratio (HR) for the intervention phase, stroke HR for
      the postintervention phase, and overall stroke HR. RESULTS: Four studies,
      involving 15,423 participants who received HT and 14,582 participants who
      received placebo, met the criteria for inclusion in the meta-analysis. The mean
      age of participants ranged from approximately 50 to 64 years. HT was given as
      conjugated equine estrogens in three studies and as 17beta-estradiol in one
      study. The duration of HT ranged from 3.0 to 10.1 years. The length of follow-up
      after the start of HT ranged from 3.0 to 15.8 years. Meta-analysis revealed that
      the stroke HR during the intervention phase and the overall stroke HR were
      significantly increased among women who received HT (intervention phase: pooled
      HR, 1.32; 95% CI, 1.12-1.56; P = 0.001; overall: pooled HR, 1.15; 95% CI, 1.03
      1.28; P = 0.017). The stroke HR during the postintervention phase was not
      increased among women who received HT (pooled HR, 1.00; 95% CI, 0.85-1.16; P =
      0.958). Sensitivity analysis confirmed the reliability of the meta-analysis for
      both outcomes. CONCLUSIONS: These findings suggest that HT may increase the risk
      of stroke during, but not after, HT in healthy postmenopausal women.

PMID- 24686451
TI  - Stem cells. Repair of renal injury gains omentum.

PMID- 24686453
TI  - Automated separation of C. elegans variably colonized by a bacterial pathogen.
AB  - The wormsorter is an instrument analogous to a FACS machine that is used in
      studies of Caenorhabditis elegans, typically to sort worms based on expression of
      a fluorescent reporter. Here, we highlight an alternative usage of this
      instrument, for sorting worms according to their degree of colonization by a GFP
      expressing pathogen. This new usage allowed us to address the relationship
      between colonization of the worm intestine and induction of immune responses.
      While C. elegans immune responses to different pathogens have been documented, it
      is still unknown what initiates them. The two main possibilities (which are not
      mutually exclusive) are recognition of pathogen-associated molecular patterns,
      and detection of damage caused by infection. To differentiate between the two
      possibilities, exposure to the pathogen must be dissociated from the damage it
      causes. The wormsorter enabled separation of worms that were extensively
      colonized by the Gram-negative pathogen Pseudomonas aeruginosa, with the damage
      likely caused by pathogen load, from worms that were similarly exposed, but not,
      or marginally, colonized. These distinct populations were used to assess the
      relationship between pathogen load and the induction of transcriptional immune
      responses. The results suggest that the two are dissociated, supporting the
      possibility of pathogen recognition. 

PMID- 24686452
TI  - Roles of phosphate and fibroblast growth factor 23 in cardiovascular disease.
AB  - Disturbances in phosphate homeostasis are common in patients with chronic kidney
      disease. As kidney function declines, circulating concentrations of phosphate and
      the phosphate-regulatory hormone, fibroblast growth factor (FGF)-23, rise
      progressively. Higher serum levels of phosphate and FGF-23 are associated with an
      increased risk of adverse outcomes, including all-cause mortality and
      cardiovascular events. The associations between higher FGF-23 levels and adverse
      cardiovascular outcomes are generally independent of serum phosphate levels, and
      might be strongest for congestive heart failure. Higher serum phosphate levels
      are also modestly associated with an increased risk of cardiovascular events even
      after accounting for FGF-23 levels. This observation suggests that FGF-23 and
      phosphate might promote distinct mechanisms of cardiovascular toxicity. Indeed,
      animal models implicate high serum phosphate as a mechanism of vascular
      calcification and endothelial dysfunction, whereas high levels of FGF-23 are
      implicated in left ventricular hypertrophy. These seemingly distinct, but perhaps
      additive, adverse effects of phosphate on the vasculature and FGF-23 on the heart
      suggest that future population-level and individual-level interventions will need
      to simultaneously target these molecules to reduce the risk of associated
      cardiovascular events. 

PMID- 24686454
TI  - Impaired innate immune alveolar macrophage response and the predilection for COPD
      exacerbations.
AB  - BACKGROUND: Alveolar macrophages (AM) in COPD have fundamentally impaired
      responsiveness to Toll-like receptor 2 (TLR2) and TLR4 ligands of non-typeable
      Haemophilus influenzae (NTHI). However, the contribution of innate immune
      dysfunction to exacerbations of COPD is unexplored. We hypothesised that impaired
      innate AM responses in COPD extend beyond NTHI to other pathogens and are linked
      with COPD exacerbations and severity. METHODS: AMs, obtained by bronchoalveolar
      lavage from 88 volunteers with stable-to-moderate COPD, were incubated with
      respiratory pathogens (NTHI, Moraxella catarrhalis (MC), Streptococcus pneumoniae
      (SP) and TLR ligands lipopolysaccharide, Pam3Cys) and elicited IL-8 and TNF-alpha
      were measured by microsphere flow cytometry. NF-kappaB nuclear translocation was
      measured by colorimetric assay. AM TLR2 and TLR4 expression was determined by
      immunolabeling and quantitation of mean fluorescent indices. Participants were
      monitored prospectively for occurrence of COPD exacerbations for 1 year following
      bronchoscopy. Non-parametric analyses were used to compare exacerbation-prone and
      non-exacerbation-prone individuals. RESULTS: 29 subjects had at least one
      exacerbation in the follow-up period (exacerbation-prone) and 59 remained
      exacerbation-free (non-exacerbation-prone). AMs of exacerbation-prone COPD donors
      were more refractory to cytokine induction by NTHI (p=0.02), MC (p=0.045) and SP
      (p=0.046), and to TLR2 (p=0.07) and TLR4 (p=0.028) ligands, and had diminished NF
      kappaB nuclear activation, compared with non-exacerbation-prone counterparts. AMs
      of exacerbation-prone subjects were more refractory to TLR2 upregulation by MC
      and SP (p=0.04 each). CONCLUSIONS: Our results support a paradigm of impaired
      innate responses of COPD AMs to respiratory pathogens, mediated by impaired TLR
      responses, underlying a propensity for exacerbations in COPD.

PMID- 24686455
TI  - Adverse prenatal environment and kidney development: implications for programing
      of adult disease.
AB  - The 'developmental origins of health and disease' hypothesis suggests that many
      adult-onset diseases can be attributed to altered growth and development during
      early life. Perturbations during gestation can be detrimental and lead to an
      increased risk of developing renal, cardiovascular, metabolic, and neurocognitive
      dysfunction in adulthood. The kidney has emerged as being especially vulnerable
      to insult at almost any stage of development resulting in a reduction in nephron
      endowment. In both humans and animal models, a reduction in nephron endowment is
      strongly associated with an increased risk of hypertension. The focus of this
      review is twofold: i) to determine the importance of specific periods during
      development on long-term programing and ii) to examine the effects of maternal
      perturbations on the developing kidney and how this may program adult-onset
      disease. Recent evidence has suggested that insults occurring around the time of
      conception also have the capacity to influence long-term health. Although
      epigenetic mechanisms are implicated in mediating these outcomes, it is unclear
      as to how these may impact on kidney development. This presents exciting new
      challenges and areas for research.

PMID- 24686457
TI  - Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous
      abortion patients.
AB  - MicroRNAs (miRNAs) are non-coding RNA molecules of about 22 nucleotides that
      involved in post-transcriptional gene regulation. Evidence indicates that miRNAs
      play essential roles in endometriosis, pre-eclampsia, infertility and other
      reproductive system diseases. However, whether miRNAs are involved in recurrent
      spontaneous abortion (RSA) is unclear. In this work, we analysed the miRNA
      expression profiles in six pairs of villus or decidua from RSA patients and
      normal pregnancy (NP) women using a human miRNA microarray. Some of the chip
      results were confirmed by RT-qPCR. In the villi of RSA patients, expression of
      hsa-miR-184, hsa-miR-187 and hsa-miR-125b-2 was significantly higher, while
      expression of hsa-miR-520f, hsa-miR-3175 and hsa-miR-4672 was significantly
      lower, comparing with those of NP control. As well, a total of five miRNAs (hsa
      miR-517c, hsa-miR-519a-1, hsa-miR-522, hsa-miR-520h and hsa-miR-184) were
      upregulated in the decidua of RSA patients. The target genes of these
      differentially expressed miRNAs were predicted by miRWalk, and we speculate a
      network of miRNA regulating RSA by target genes function on adhesion, apoptosis
      and angiogenesis. Our study may help clarify the molecular mechanisms which are
      involved in the progression of RSA, and provide a reference for future research. 

PMID- 24686456
TI  - Effects of IL8 and immune cells on the regulation of luteal progesterone
      secretion.
AB  - Recent studies have suggested that chemokines may mediate the luteolytic action
      of prostaglandin F2alpha (PGF). Our objective was to identify chemokines induced
      by PGF in vivo and to determine the effects of interleukin 8 (IL8) on specific
      luteal cell types in vitro. Mid-cycle cows were injected with saline or PGF,
      ovaries were removed after 0.5-4 h, and expression of chemokine was analyzed by
      qPCR. In vitro expression of IL8 was analyzed after PGF administration and with
      cell signaling inhibitors to determine the mechanism of PGF-induced chemokine
      expression. Purified neutrophils were analyzed for migration and activation in
      response to IL8 and PGF. Purified luteal cell types (steroidogenic, endothelial,
      and fibroblast cells) were used to identify which cells respond to chemokines.
      Neutrophils and peripheral blood mononuclear cells (PBMCs) were cocultured with
      steroidogenic cells to determine their effect on progesterone production. IL8,
      CXCL2, CCL2, and CCL8 transcripts were rapidly increased following PGF treatment
      in vivo. The stimulatory action of PGF on IL8 mRNA expression in vitro was
      prevented by inhibition of p38 and JNK signaling. IL8, but not PGF, TNF, or
      TGFB1, stimulated neutrophil migration. IL8 had no apparent action in purified
      luteal steroidogenic, endothelial, or fibroblast cells, but stimulated ERK
      phosphorylation in neutrophils. In coculture experiments neither IL8 nor
      activated neutrophils altered basal or LH-stimulated luteal cell progesterone
      synthesis. In contrast, activated PBMCs inhibited LH-stimulated progesterone
      synthesis from cultured luteal cells. These data implicate a complex cascade of
      events during luteolysis, involving chemokine signaling, neutrophil recruitment,
      and immune cell action within the corpus luteum. 

PMID- 24686458
TI  - microRNA 376a regulates follicle assembly by targeting Pcna in fetal and neonatal
      mouse ovaries.
AB  - In mammals, the primordial follicle pool, providing all oocytes available to a
      female throughout her reproductive life, is established perinatally.
      Dysregulation of primordial follicle assembly results in female reproductive
      diseases, such as premature ovarian insufficiency and infertility. Female mice
      lacking Dicer1 (Dicer), a gene required for biogenesis of microRNAs, show
      abnormal morphology of follicles and infertility. However, the contribution of
      individual microRNAs to primordial follicle assembly remains largely unknown.
      Here, we report that microRNA 376a (miR-376a) regulates primordial follicle
      assembly by modulating the expression of proliferating cell nuclear antigen
      (Pcna), a gene we previously reported to regulate primordial follicle assembly by
      regulating oocyte apoptosis in mouse ovaries. miR-376a was shown to be negatively
      correlated with Pcna mRNA expression in fetal and neonatal mouse ovaries and to
      directly bind to Pcna mRNA 3' untranslated region. Cultured 18.5 days postcoitum
      mouse ovaries transfected with miR-376a exhibited decreased Pcna expression both
      in protein and mRNA levels. Moreover, miR-376a overexpression significantly
      increased primordial follicles and reduced apoptosis of oocytes, which was very
      similar to those in ovaries co-transfected with miR-376a and siRNAs targeting
      Pcna. Taken together, our results demonstrate that miR-376a regulates primordial
      follicle assembly by modulating the expression of Pcna. To our knowledge, this is
      the first microRNA-target mRNA pair that has been reported to regulate mammalian
      primordial follicle assembly and further our understanding of the regulation of
      primordial follicle assembly. 

PMID- 24686459
TI  - Maternal age effect on mouse oocytes: new biological insight from proteomic
      analysis.
AB  - The long-standing view of 'immortal germline vs mortal soma' poses a fundamental
      question in biology concerning how oocytes age in molecular terms. A mainstream
      hypothesis is that maternal ageing of oocytes has its roots in gene
      transcription. Investigating the proteins resulting from mRNA translation would
      reveal how far the levels of functionally available proteins correlate with mRNAs
      and would offer novel insights into the changes oocytes undergo during maternal
      ageing. Gene ontology (GO) semantic analysis revealed a high similarity of the
      detected proteome (2324 proteins) to the transcriptome (22 334 mRNAs), although
      not all proteins had a cognate mRNA. Concerning their dynamics, fourfold changes
      of abundance were more frequent in the proteome (3%) than the transcriptome
      (0.05%), with no correlation. Whereas proteins associated with the nucleus (e.g.
      structural maintenance of chromosomes and spindle-assembly checkpoints) were
      largely represented among those that change in oocytes during maternal ageing;
      proteins associated with oxidative stress/damage (e.g. superoxide dismutase) were
      infrequent. These quantitative alterations are either impoverishing or enriching.
      Using GO analysis, these alterations do not relate in any simple way to the
      classic signature of ageing known from somatic tissues. Given the lack of
      correlation, we conclude that proteome analysis of mouse oocytes may not be
      surrogated with transcriptome analysis. Furthermore, we conclude that the classic
      features of ageing may not be transposed from somatic tissues to oocytes in a one
      to-one fashion. Overall, there is more to the maternal ageing of oocytes than
      mere cellular deterioration exemplified by the notorious increase of meiotic
      aneuploidy. 

PMID- 24686460
TI  - Role of maternal gesture use in speech use by children with fragile X syndrome.
AB  - PURPOSE: The purpose of this study was to investigate how maternal gesture
      relates to speech production by children with fragile X syndrome (FXS). METHOD:
      Participants were 27 young children with FXS (23 boys, 4 girls) and their
      mothers. Videotaped home observations were conducted between the ages of 25 and
      37 months (toddler period) and again between the ages of 60 and 71 months (child
      period). The videos were later coded for types of maternal utterances and
      maternal gestures that preceded child speech productions. Children were also
      assessed with the Mullen Scales of Early Learning at both ages. RESULTS: Maternal
      gesture use in the toddler period was positively related to expressive language
      scores at both age periods and was related to receptive language scores in the
      child period. Maternal proximal pointing, in comparison to other gestures, evoked
      more speech responses from children during the mother-child interactions,
      particularly when combined with wh-questions. CONCLUSION: This study adds to the
      growing body of research on the importance of contextual variables, such as
      maternal gestures, in child language development. Parental gesture use may be an
      easily added ingredient to parent-focused early language intervention programs.

PMID- 24686462
TI  - Thioredoxin-interacting protein, hematopoietic stem cells, and hematopoiesis.
AB  - PURPOSE OF REVIEW: Reactive oxygen species (ROS) can regulate diverse signaling
      pathways and functions in hematopoietic cells. Thioredoxin-interacting protein
      (TXNIP) plays an important role in mammalian cells by inhibiting thioredoxin
      (TRX) under oxidative stress conditions. TXNIP is expressed in hematopoietic stem
      cells (HSCs), and its expression decreases as HSCs differentiate into precursor
      cells. However, this reduction in expression does not sufficiently explain the
      function of TXNIP in hematopoietic cells under oxidative stress conditions. Here,
      we review how ROS can regulate hematopoiesis by focusing on the function of TXNIP
      in hematopoietic cells under oxidative stress conditions. RECENT FINDINGS:
      Studies of Txnip mice have demonstrated an antioxidant function of TXNIP in
      hematopoietic cells or immune cells. This antioxidant function differs from the
      conventional pro-oxidant activity of TXNIP observed in other cell types under
      oxidative stress. The data suggest a context-dependent function of TXNIP under
      oxidative stress conditions and, in particular, a differential function of TXNIP
      in hematopoietic cells via its direct interaction with other redox regulatory
      proteins. SUMMARY: The regulation of ROS is important in determining cellular
      fate decisions. TXNIP acts as a negative regulator of TRX via direct interaction,
      and it increases the levels of ROS under oxidative stress. However, TXNIP has an
      antioxidant function in hematopoietic cells or immune cells, as ROS levels are
      elevated and induce apoptosis in Txnip hematopoietic cells. These results suggest
      that the amount of TXNIP is inversely associated with ROS levels, and the loss of
      TXNIP can increase ROS levels in immune cells or hematopoietic cells.

PMID- 24686461
TI  - Electrochemiluminescence resonance energy transfer between graphene quantum dots
      and gold nanoparticles for DNA damage detection.
AB  - Bright blue luminescent graphene quantum dots (GQDs) with major graphitic
      structured nanocrystals and a photoluminescence (PL) quantum yield of 15.5% were
      synthesized and used to monitor DNA damage. The GQDs were prepared by ultraviolet
      irradiation without using a chemical agent. The as-prepared GQDs showed
      excitation-dependent PL and stable electrochemiluminescence (ECL) behaviors. Gold
      nanoparticles (AuNPs) were linked with a probe of single-stranded DNA (cp53
      ssDNA) to form AuNPs-ssDNA. The ECL signal of the GQDs could be quenched by non
      covalent binding of the AuNPs-ssDNA to the GQDs, due to the occurrence of an
      electrochemiluminescence resonance energy transfer between the GQDs and the
      AuNPs. When AuNPs-ssDNA was then hybridized with target p53 DNA to form AuNPs
      dsDNA, the non-covalent interaction between the GQDs and the ds-DNA weakened and
      the ECL of the GQDs recovered. This engendered an ECL sensor for the detection of
      target p53 ssDNA, with a detection limit of 13 nM. The resultant ECL sensor could
      be used for DNA damage detection based on its different bonding ability to
      damaged target p53 ssDNA and cp53 ssDNA linked AuNPs. The presented method could
      be expanded to the development of other ECL biosensors, for the quantification of
      nucleic acids, single nucleotide polymorphisms or other aptamer-specific
      biomolecules. 

PMID- 24686463
TI  - Does brain volume loss predict cognitive and narrative discourse performance
      following traumatic brain injury?
AB  - PURPOSE: In this study, the authors investigated the relationship between brain
      volume loss and performance on cognitive measures, including working memory,
      immediate memory, executive functions, and intelligence, and a narrative
      discourse production task. An underlying goal was to examine the prognostic
      potential of a brain lesion metric for discourse outcomes. It was hypothesized
      that brain volume loss would correlate with and predict cognitive and narrative
      discourse measures and have prognostic value for discourse outcomes. METHOD: One
      hundred sixty-seven individuals with penetrating head injury participated.
      Correlational and regression analyses were performed for the percentages of total
      brain and hemispheric volume loss and scores on 4 cognitive measures (WMS-III
      Working Memory and Immediate Memory primary indexes, D-KEFS Sorting Test, and
      WAIS-III Full Scale IQ) and 7 narrative discourse measures (T-units, grammatical
      complexity, cohesion, local and global coherence, story completeness, and story
      grammar). RESULTS: The volumetric measures had significant small-to-moderate
      correlations with all cognitive measures but only one significant correlation
      with the discourse measures. Findings from regression analyses were analogous but
      revealed several models that approached significance. CONCLUSION: Findings
      suggest that an overall measure of brain damage may be more predictive of general
      cognitive status than of narrative discourse ability. Atrophy measures in
      specific brain regions may be more informative.

PMID- 24686464
TI  - Structure of organic solids at low temperature and high pressure.
AB  - This tutorial review looks at structural and supramolecular chemistry of
      molecular solids under extreme conditions, and introduces the instrumentation and
      facilities that enable single crystal diffraction studies on molecular crystals
      at both high pressure and low temperature. The equipment used for crystallography
      under extreme conditions is explored, particularly pressure cells such as the
      diamond anvil cell, and their mechanism of action, as well as the cryogenic
      apparatus which allows materials to be cooled to significantly low temperatures.
      The review also covers recent advances in the structural chemistry of molecular
      solids under extreme conditions with an emphasis on the use of single crystal
      crystallography in high pressure and low temperature environments to probe
      polymorphism and supramolecular interactions. 

PMID- 24686465
TI  - [Leg ulcers in patients with sickle-cell disease in Libreville (Gabon): clinical
      aspects and management].
AB  - OBJECTIVES: To present the clinical aspects of leg ulcers among patients with
      sickle-cell disease, propose a protocol for treating them, and identify risk
      factors for their onset in our patients. PATIENTS AND METHODS: This 5-year
      retrospective descriptive study (2007-2012) includes six adolescents homozygous
      (SS) for this disease who had at least one leg ulcer during the study period.
      RESULTS: Our population was aged 16-20 years and comprised 4 young men and 2
      young women. Signs at diagnosis included pallor (100%), jaundice (100%),
      splenomegaly (80%), and fever (70%). Painful crises most often involved a vaso
      occlusive crisis (42%), followed by a splenic sequestration crisis (27%), a
      hemolytic crisis (18%), and erythroblastopenia (14%). CONCLUSION: Leg ulcers are
      a complication of sickle cell disease and cause esthetic, psychological, and
      economic problems. Prevention involves patient education to prevent the
      occurrence and recurrence of these ulcers.

PMID- 24686466
TI  - Effects of phonetic context on relative fundamental frequency.
AB  - PURPOSE: The effect of phonetic context on relative fundamental frequency (RFF)
      was examined, in order to develop stimuli sets with minimal within-speaker
      variability that can be implemented in future clinical protocols. METHOD: Sixteen
      speakers with healthy voices produced RFF stimuli. Uniform utterances consisted
      of 3 repetitions of the same voiced sonorant-voiceless consonant-voiced sonorant
      speech sequence; moderately variable sentences contained speech sequences with a
      single voiceless phoneme (/f/, /s/, /?/, /p/, /t/, or /k/); highly variable
      sentences were loaded with speech sequences using multiple phonemes. Effects of
      stimulus type (uniform, moderately variable, and highly variable) and phoneme
      identity (/f/, /s/, /?/, /p/, /t/, and /k/) on RFF means and standard deviations
      were determined. RESULTS: Stimulus type and the interaction of vocal cycle and
      stimulus type were significant for RFF means and standard deviations but with
      small effect sizes. Phoneme identity and the interaction of vocal cycle and
      phoneme identity on RFF means and standard deviations were also significant with
      small to medium effect sizes. CONCLUSIONS: For speakers with healthy voices,
      uniform utterances with /f/ and /?/ have the lowest standard deviations and thus
      are recommended for RFF-based assessments. Future work is necessary to extend
      these findings to disordered voices.

PMID- 24686467
TI  - Spatial and temporal lingual coarticulation and motor control in preadolescents.
AB  - PURPOSE In this study, the authors compared coarticulation and lingual kinematics
      in preadolescents and adults in order to establish whether preadolescents had a
      greater degree of random variability in tongue posture and whether their patterns
      of lingual coarticulation differed from those of adults. METHOD High-speed
      ultrasound tongue contour data synchronized with the acoustic signal were
      recorded from 15 children (ages 10-12 years) and 15 adults. Tongue shape contours
      were analyzed at 9 normalized time points during the fricative phase of schwa
      fricative-/a/ and schwa-fricative-/i/ sequences with the consonants /s/ and /?/.
      RESULTS There was no significant age-related difference in random variability.
      Where a significant vowel effect occurred, the amount of coarticulation was
      similar in the 2 groups. However, the onset of the coarticulatory effect on
      preadolescent /?/ was significantly later than on preadolescent /s/, and also
      later than on adult /s/ and /?/. CONCLUSIONS Preadolescents have adult-like
      precision of tongue control and adult-like anticipatory lingual coarticulation
      with respect to spatial characteristics of tongue posture. However, there remains
      some immaturity in the motor programming of certain complex tongue movements. 

PMID- 24686469
TI  - Relation between pretransplant magnesemia and the risk of new onset diabetes
      after transplantation within the first year of kidney transplantation.
AB  - BACKGROUND: New-onset diabetes after transplantation (NODAT) is a frequent
      condition associated with a poor outcome. In kidney transplantation,
      hypomagnesemia is a frequent posttransplant complication and has been associated
      with calcineurin inhibitors use. Previous studies have analyzed the relationship
      between posttransplant hypomagnesemia and the risk of NODAT and provided
      conflicting conclusions. We conducted an observational study to analyze the
      relationship between pretransplant magnesemia (Mg) and the risk of NODAT within
      the first year of kidney transplantation. METHODS: A cohort study was conducted
      to determine the risk conferred by pretransplant magnesium level on development
      of NODAT within 1 year posttransplant. First time kidney transplant recipients
      between January 2005 and December 2010 with more than 6 months of follow-up were
      included. Mg was measured within the 24 hours preceding kidney transplantation.
      NODAT was defined according to the American Diabetes Association criteria.
      RESULTS: Among the 154 patients analyzed, 28 (18.2%) developed NODAT at year 1.
      NODAT patients had lower levels of pretransplant Mg as compared with non-NODAT
      patients (P<0.02). When patients were divided into tertiles of Mg level, NODAT
      developed more frequently in patients in the lower tertile (Mg <2 mg/dL) as
      compared with patients in the higher tertile (Mg >2.3 mg/dL) (log rank, P<0.05).
      A multivariate analysis after adjustment to several variables demonstrated
      pretransplant Mg to be an independent risk factor of NODAT. CONCLUSION: This
      study supports that a low pretransplant Mg level is an independent risk factor of
      NODAT in kidney transplant recipients.

PMID- 24686468
TI  - A comparison of pragmatic language in boys with autism and fragile X syndrome.
AB  - PURPOSE: Impaired pragmatic language (i.e., language use for social interaction)
      is a hallmark feature of both autism spectrum disorder (ASD) and fragile X
      syndrome (FXS), the most common known monogenic disorder associated with ASD.
      However, few cross-population comparisons of ASD and FXS have been conducted, and
      it is unclear whether pragmatic language profiles in these conditions overlap.
      METHOD: The authors used seminaturalistic and standardized assessment methods to
      characterize pragmatic language abilities of 29 school-aged boys with idiopathic
      ASD, 38 with FXS and comorbid ASD, 16 with FXS without ASD, 20 with Down
      syndrome, and 20 with typical development. RESULTS: Similar severity of pragmatic
      language deficits was observed in both of the groups with ASD (idiopathic and
      fragile X-associated). ASD comorbidity had a detrimental effect on the pragmatic
      language skills of the boys with FXS. Some different patterns emerged across the
      two pragmatic assessment tools, with more robust group differences observed in
      pragmatics assessed in a seminaturalistic conversational context. CONCLUSION:
      These findings have implications for pragmatic language assessment and
      intervention, as well as for understanding the potential role of the fragile X
      gene, Fragile X Mental Retardation-1, in the pragmatic language phenotype of ASD.

PMID- 24686470
TI  - Tissue-point motion tracking in the tongue from cine MRI and tagged MRI.
AB  - PURPOSE Accurate tissue motion tracking within the tongue can help professionals
      diagnose and treat vocal tract-related disorders, evaluate speech quality before
      and after surgery, and conduct various scientific studies. The authors compared
      tissue tracking results from 4 widely used deformable registration (DR) methods
      applied to cine magnetic resonance imaging (MRI) with harmonic phase (HARP)-based
      tracking applied to tagged MRI. METHOD Ten subjects repeated the phrase "a geese"
      multiple times while sagittal images of the head were collected at 26 Hz, first
      in a tagged MRI data set and then in a cine MRI data set. HARP tracked the motion
      of 8 specified tissue points in the tagged data set. Four DR methods including
      diffeomorphic demons and free-form deformations based on cubic B-spline with 3
      different similarity measures were used to track the same 8 points in the cine
      MRI data set. Individual points were tracked and length changes of several
      muscles were calculated using the DR- and HARP-based tracking methods. RESULTS
      The results showed that the DR tracking errors were nonsystematic and varied in
      direction, amount, and timing across speakers and within speakers. Comparison of
      HARP and DR tracking with manual tracking showed better tracking results for HARP
      except at the tongue surface, where mistracking caused greater errors in HARP
      than DR. CONCLUSIONS Tissue point tracking using DR tracking methods contains
      nonsystematic tracking errors within and across subjects, making it less
      successful than tagged MRI tracking within the tongue. However, HARP sometimes
      mistracks points at the tongue surface of tagged MRI because of its limited
      bandpass filter and tag pattern fading, so that DR has better success measuring
      surface tissue points on cine MRI than HARP does. Therefore, a hybrid method is
      being explored. 

PMID- 24686476
TI  - Children's reaction to depictions of healthy foods in fast-food television
      advertisements.
AB  - IMPORTANCE: Since 2009, quick-service restaurant chains, or fast-food companies,
      have agreed to depict healthy foods in their advertising targeted at children.
      OBJECTIVE: To determine how children interpreted depictions of milk and apples in
      television advertisements for children's meals by McDonald's and Burger King (BK)
      restaurants. DESIGN, SETTING, AND PARTICIPANTS: Descriptive qualitative study in
      a rural pediatric practice setting in Northern New England. A convenience sample
      of 99 children (age range, 3-7 years) was shown depictions of healthy foods in
      fast-food advertisements that aired from July 1, 2010, through June 30, 2011. The
      images from McDonald's and BK showed milk and apples. Children were asked what
      they saw and not prompted to respond specifically to any aspect of the images.
      EXPOSURE: Two still images drawn from advertisements for healthy meals at
      McDonald's and BK. MAIN OUTCOMES AND MEASURES: Children's responses were
      independently content coded to food category by 2 researchers. RESULTS: Among the
      99 children participating, only 51 (52%) and 69 (70%) correctly identified milk
      from the McDonald's and BK images, respectively, with a significantly greater
      percentage correct (P = .02 for both) among older children. The children's recall
      of apples was significantly different by restaurant, with 79 (80%) mentioning
      apples when describing the McDonald's image and only 10 (10%) for the BK image (P
      < .001). The percentage correct was not associated with age in either case.
      Conversely, although french fries were not featured in either image, 80 children
      (81%) recalled french fries after viewing the BK advertisement. CONCLUSIONS AND
      RELEVANCE: Of the 4 healthy food images, only depiction of apples by McDonald's
      was communicated adequately to the target audience. Representations of milk were
      inadequately communicated to preliterate children. Televised depictions of apple
      slices by BK misled the children in this study, although no action was taken by
      government or self-regulatory bodies.

PMID- 24686475
TI  - Solenopsis invicta virus 3: mapping of structural proteins, ribosomal
      frameshifting, and similarities to Acyrthosiphon pisum virus and Kelp fly virus.
AB  - Solenopsis invicta virus 3 (SINV-3) is a positive-sense single-stranded RNA virus
      that infects the red imported fire ant, Solenopsis invicta. We show that the
      second open reading frame (ORF) of the dicistronic genome is expressed via a
      frameshifting mechanism and that the sequences encoding the structural proteins
      map to both ORF2 and the 3' end of ORF1, downstream of the sequence that encodes
      the RNA-dependent RNA polymerase. The genome organization and structural protein
      expression strategy resemble those of Acyrthosiphon pisum virus (APV), an aphid
      virus. The capsid protein that is encoded by the 3' end of ORF1 in SINV-3 and APV
      is predicted to have a jelly-roll fold similar to the capsid proteins of
      picornaviruses and caliciviruses. The capsid-extension protein that is produced
      by frameshifting, includes the jelly-roll fold domain encoded by ORF1 as its N
      terminus, while the C-terminus encoded by the 5' half of ORF2 has no clear
      homology with other viral structural proteins. A third protein, encoded by the 3'
      half of ORF2, is associated with purified virions at sub-stoichiometric ratios.
      Although the structural proteins can be translated from the genomic RNA, we show
      that SINV-3 also produces a subgenomic RNA encoding the structural proteins.
      Circumstantial evidence suggests that APV may also produce such a subgenomic RNA.
      Both SINV-3 and APV are unclassified picorna-like viruses distantly related to
      members of the order Picornavirales and the family Caliciviridae. Within this
      grouping, features of the genome organization and capsid domain structure of SINV
      3 and APV appear more similar to caliciviruses, perhaps suggesting the basis for
      a "Calicivirales" order. 

PMID- 24686477
TI  - Quantitative passive soil vapor sampling for VOCs--Part 4: Flow-through cell.
AB  - This paper presents a controlled experiment comparing several quantitative
      passive samplers for monitoring concentrations of volatile organic compound (VOC)
      vapors in soil gas using a flow-through cell. This application is simpler than
      conventional active sampling using adsorptive tubes because the flow rate does
      not need to be precisely measured and controlled, which is advantageous because
      the permeability of subsurface materials affects the flow rate and the
      permeability of geologic materials is highly variable. Using passive samplers in
      a flow-through cell, the flow rate may not need to be known exactly, as long as
      it is sufficient to purge the cell in a reasonable time and minimize any negative
      bias attributable to the starvation effect. An experiment was performed in a 500
      mL flow-through cell using a two-factor, one-half fraction fractional factorial
      test design with flow rates of 80, 670 and 930 mL min(-1) and sample durations of
      10, 15 and 20 minutes for each of five different passive samplers (passive
      Automatic Thermal Desorption Tube, Radiello(r), SKC Ultra, Waterloo Membrane
      SamplerTM and 3MTM OVM 3500). A Summa canister was collected coincident with each
      passive sampler and analyzed by EPA Method TO-15 to provide a baseline for
      comparison of the passive sampler concentrations. The passive sampler
      concentrations were within a factor of 2 of the Summa canister concentrations in
      32 of 35 cases. Passive samples collected at the low flow rate and short duration
      showed low concentrations, which is likely attributable to insufficient purging
      of the cell after sampler placement. 

PMID- 24686478
TI  - Visualization of the immunological synapse by dual color time-gated stimulated
      emission depletion (STED) nanoscopy.
AB  - Natural killer cells form tightly regulated, finely tuned immunological synapses
      (IS) in order to lyse virally infected or tumorigenic cells. Dynamic actin
      reorganization is critical to the function of NK cells and the formation of the
      IS. Imaging of F-actin at the synapse has traditionally utilized confocal
      microscopy, however the diffraction limit of light restricts resolution of
      fluorescence microscopy, including confocal, to approximately 200 nm. Recent
      advances in imaging technology have enabled the development of subdiffraction
      limited super-resolution imaging. In order to visualize F-actin architecture at
      the IS we recapitulate the NK cell cytotoxic synapse by adhering NK cells to
      activating receptor on glass. We then image proteins of interest using two-color
      stimulated emission depletion microscopy (STED). This results in <80 nm
      resolution at the synapse. Herein we describe the steps of sample preparation and
      the acquisition of images using dual color STED nanoscopy to visualize F-actin at
      the NK IS. We also illustrate optimization of sample acquisition using Leica SP8
      software and time-gated STED. Finally, we utilize Huygens software for post
      processing deconvolution of images. 

PMID- 24686480
TI  - Mouse hindbrain ex vivo culture to study facial branchiomotor neuron migration.
AB  - Embryonic neurons are born in the ventricular zone of the brain, but subsequently
      migrate to new destinations to reach appropriate targets. Deciphering the
      molecular signals that cooperatively guide neuronal migration in the embryonic
      brain is therefore important to understand how the complex neural networks form
      which later support postnatal life. Facial branchiomotor (FBM) neurons in the
      mouse embryo hindbrain migrate from rhombomere (r) 4 caudally to form the paired
      facial nuclei in the r6-derived region of the hindbrain. Here we provide a
      detailed protocol for wholemount ex vivo culture of mouse embryo hindbrains
      suitable to investigate the signaling pathways that regulate FBM migration. In
      this method, hindbrains of E11.5 mouse embryos are dissected and cultured in an
      open book preparation on cell culture inserts for 24 hr. During this time, FBM
      neurons migrate caudally towards r6 and can be exposed to function-blocking
      antibodies and small molecules in the culture media or heparin beads loaded with
      recombinant proteins to examine roles for signaling pathways implicated in
      guiding neuronal migration. 

PMID- 24686481
TI  - Indo-Pacific warm pool area expansion, Modoki activity, and tropical cold-point
      tropopause temperature variations.
AB  - The tropical cold-point tropopause temperature (CPTT), a potentially important
      indicator of global climate change, is of particular importance for understanding
      changes in stratospheric water vapor levels. Since the 1980s, the tropical CPTT
      has shown not only interannual variations, but also a decreasing trend. However,
      the factors controlling the variations in the tropical CPTT since the 1980s
      remain elusive. The present study reveals that the continuous expansion of the
      area of the Indo-Pacific warm pool (IPWP) since the 1980s represents an increase
      in the total heat energy of the IPWP available to heat the tropospheric air,
      which is likely to expand as a result. This process lifts the tropical cold-point
      tropopause height (CPTH) and leads to the observed long-term cooling trend of the
      tropical CPTT. In addition, our analysis shows that Modoki activity is an
      important factor in modulating the interannual variations of the tropical CPTT
      through significant effects on overshooting convection. 

PMID- 24686479
TI  - The Vibrio cholerae type VI secretion system employs diverse effector modules for
      intraspecific competition.
AB  - Vibrio cholerae is a Gram-negative bacterial pathogen that consists of over 200
      serogroups with differing pathogenic potential. Only strains that express the
      virulence factors cholera toxin (CT) and toxin-coregulated pilus (TCP) are
      capable of pandemic spread of cholera diarrhoea. Regardless, all V. cholerae
      strains sequenced to date harbour genes for the type VI secretion system (T6SS)
      that translocates effectors into neighbouring eukaryotic and prokaryotic cells.
      Here we report that the effectors encoded within these conserved gene clusters
      differ widely among V. cholerae strains, and that immunity proteins encoded
      immediately downstream from the effector genes protect their host from
      neighbouring bacteria producing corresponding effectors. As a consequence,
      strains with matching effector-immunity gene sets can coexist, while strains with
      different sets compete against each other. Thus, the V. cholerae T6SS contributes
      to the competitive behaviour of this species. 

PMID- 24686482
TI  - Multiple sclerosis: could simvastatin slow down secondary progressive MS?

PMID- 24686483
TI  - Traumatic brain injury: blood biomarkers for assessing concussion in professional
      hockey players.

PMID- 24686485
TI  - The next 75 years.

PMID- 24686484
TI  - Accuracy and precision of a custom camera-based system for 2-d and 3-d motion
      tracking during speech and nonspeech motor tasks.
AB  - PURPOSE Studying normal or disordered motor control requires accurate motion
      tracking of the effectors (e.g., orofacial structures). The cost of
      electromagnetic, optoelectronic, and ultrasound systems is prohibitive for many
      laboratories and limits clinical applications. For external movements (lips,
      jaw), video-based systems may be a viable alternative, provided that they offer
      high temporal resolution and submillimeter accuracy. METHOD The authors examined
      the accuracy and precision of 2-D and 3-D data recorded with a system that
      combines consumer-grade digital cameras capturing 60, 120, or 240 frames per
      second (fps), retro-reflective markers, commercially available computer software
      (APAS, Ariel Dynamics), and a custom calibration device. RESULTS Overall root
      mean-square error (RMSE) across tests was 0.15 mm for static tracking and 0.26 mm
      for dynamic tracking, with corresponding precision (SD) values of 0.11 and 0.19
      mm, respectively. The effect of frame rate varied across conditions, but,
      generally, accuracy was reduced at 240 fps. The effect of marker size (3- vs. 6
      mm diameter) was negligible at all frame rates for both 2-D and 3-D data.
      CONCLUSION Motion tracking with consumer-grade digital cameras and the APAS
      software can achieve submillimeter accuracy at frame rates that are appropriate
      for kinematic analyses of lip/jaw movements for both research and clinical
      purposes. 

PMID- 24686486
TI  - Illusory recovery: are recovered children with early language delay at continuing
      elevated risk?
AB  - PURPOSE: To examine the later development of language and literacy of children
      who had delayed language at age 2 but were in the normal range at age 4. METHOD:
      Longitudinal data were analyzed from 3,598 pairs of twins participating in the
      Twins Early Development Study (TEDS). Six hundred thirty-three twins (8.8%) were
      delayed at age 2 based on parent-reported expressive vocabulary, and of these,
      373 (59.0%) were classified as recovered based on 4-year measures. Each recovered
      4-year-old was matched on vocabulary, gender, and zygosity to another 4-year-old
      without a history of early delay. RESULTS: Although the recovered group was below
      the mean for the total TEDS sample on measures of language at ages 7 and 12,
      there were no significant differences between the recovered and matched groups.
      Within the recovered group, it was not possible to predict outcome at better than
      a chance level. CONCLUSIONS: Children who appear to have recovered by age 4 from
      early delay are at modest risk for continuing difficulties, but this appears to
      be no higher than the risk for other 4-year-olds with equivalent scores,
      reflecting the continuing variability in longitudinal outcome after age 4. All
      children in the low normal range at age 4 merit continuing monitoring.

PMID- 24686487
TI  - Using a theoretical framework to investigate whether the HIV/AIDS information
      needs of the AfroAIDSinfo Web portal members are met: a South African eHealth
      study.
AB  - eHealth has been identified as a useful approach to disseminate HIV/AIDS
      information. Together with Consumer Health Informatics (CHI), the Web-to-Public
      Knowledge Transfer Model (WPKTM) has been applied as a theoretical framework to
      identify consumer needs for AfroAIDSinfo, a South African Web portal. As part of
      the CHI practice, regular eSurveys are conducted to determine whether these needs
      are changing and are continually being met. eSurveys show high rates of
      satisfaction with the content as well as the modes of delivery. The nature of
      information is thought of as reliable to reuse; both for education and for
      referencing of information. Using CHI and the WPKTM as a theoretical framework,
      it ensures that needs of consumers are being met and that they find the tailored
      methods of presenting the information agreeable. Combining ICTs and theories in
      eHealth interventions, this approach can be expanded to deliver information in
      other sectors of public health. 

PMID- 24686489
TI  - The scalable pinacol coupling reaction utilizing the inorganic electride
      [Ca2N](+).e(-) as an electron donor.
AB  - The scalable pinacol coupling reaction is realized utilizing the inorganic
      electride [Ca2N](+).e(-) as an electron donor in organic solvents. The bond
      cleavages of the [Ca2N](+) layers by methanol play a vital role in transferring
      anionic electrons to electrophilic aldehydes, accompanying the formation of
      Ca(OMe)2 and ammonia. 

PMID- 24686488
TI  - Hypertension in obese type 2 diabetes patients is associated with increases in
      insulin resistance and IL-6 cytokine levels: potential targets for an efficient
      preventive intervention.
AB  - Increased body weight as well as type 2 diabetes (T2D) are found to be associated
      with increased incidence of hypertension, although the mechanisms facilitating
      hypertension in T2D or nondiabetic individuals are not clear. Therefore, in this
      study we compared the levels of insulin resistance (IR:OGIS), plasma insulin
      (PI:RIA) levels, and pro-inflammatory cytokines (IL-6 and TNF-alpha: ELISA),
      being risk factors previously found to be associated with hypertension, in T2D
      patients showing increased body weight (obese and overweight, BMI >= 25 kg/m2)
      with hypertension (group A, N = 30), or without hypertension (group B, N = 30),
      and in nonobese (BMI < 25 kg/m2), normotensive controls (group C, N = 15). We
      found that OGIS index was the lowest (A: 267 +/- 35.42 vs. B: 342.89 +/- 32.0, p
      < 0.01) and PI levels were the highest (A: 31.05 +/- 8.24 vs. B: 17.23 +/- 3.23,
      p < 0.01) in group A. In addition, IL-6 levels were higher in group A (A: 15.46
      +/- 5.15 vs. B: 11.77 +/- 6.09; p < 0.05) while there was no difference in TNF
      alpha levels. Our results have shown that appearance of hypertension in T2D
      patients with increased body weight was dependent on further increase in IR which
      was associated with the rise in pro-inflammatory IL-6 cytokine. The results imply
      that lifestyle intervention aimed to decrease IR might be beneficial in reducing
      the risk for hypertension in those T2D individuals.

PMID- 24686490
TI  - Major anthropogenic causes for and outcomes of wild animal presentation to a
      wildlife clinic in East Tennessee, USA, 2000-2011.
AB  - To determine the reasons for presentation and outcome of wildlife cases in East
      Tennessee, a retrospective analysis was performed using 14,303 records from cases
      presented to the wildlife clinic of the University of Tennessee Veterinary
      Teaching Hospital between 2000 and 2011. The cases were first categorized into
      amphibian/non-avian reptile, mammal, or avian and then classified into groups
      based on the primary admitting/presenting sign. There are a variety of reasons
      animals were presented to the clinic, and some were directly or indirectly
      anthropogenic in origin, including cat related, dog related, hit by automobile,
      and other human encounters leading to trauma; of the cases reviewed, 4,443
      (31.1%) presented for one of these 4 reasons. Overall case fatality risk in
      regard to these 4 admitting/presenting signs was 0.519 for the amphibian/non
      avian reptile cases, 0.675 for mammal cases, and 0.687 for avian cases. This
      study confirms the importance of monitoring wildlife morbidity and mortality and
      of focusing efforts to reduce the anthropogenic threat on native habitats and
      resident wildlife populations. 

PMID- 24686491
TI  - Auditory neuropathy spectrum disorder: a review.
AB  - PURPOSE: Auditory neuropathy spectrum disorder, or ANSD, can be a confusing
      diagnosis to physicians, clinicians, those diagnosed, and parents of children
      diagnosed with the condition. The purpose of this review is to provide the reader
      with an understanding of the disorder, the limitations in current tools to
      determine site(s) of lesion, and management techniques. METHOD: This article is a
      review of what is known about ANSD. It includes descriptions of assessment tools,
      causes of ANSD, and patient management techniques. CONCLUSIONS: This review is a
      guide to audiologists, speech-language pathologists, and early interventionists
      who work with individuals diagnosed with ANSD and/or their families. It
      highlights the need for more precise tools to describe the disorder in order to
      facilitate decisions about interventions and lead to better predictions of
      outcome.

PMID- 24686492
TI  - Coupling dynamics interlip coordination in lower lip load compensation.
AB  - PURPOSE To study the effects of lower lip loading on lower and upper lip
      movements and their coordination to test predictions on coupling dynamics derived
      from studies in limb control. METHOD Movement data were acquired using
      electromagnetic midsagittal articulography under 4 conditions: (a) without
      restrictions, serving as a baseline; (b) with a small carrier device attached to
      the lower lip; (c) with a 50-g weight added to the device; and, at the end of the
      session (d) with the weight and device removed. For all conditions, 8
      participants repeated nonwords at 2 speaking rates. Movement data were used to
      derive discrete kinematic measures, a cyclic index of spatiotemporal variability,
      phase deviations, and standard deviations of relative phase for interlip
      coupling. RESULTS Kinematic variables were not systematically affected by lower
      lip load. Phase deviations also showed no change, but in contrast, phase
      variability showed a significant increase for the lower lip load condition at
      fast rates. CONCLUSION Lower lip load effects are comparable to the reported
      impact of homologous limb loading, showing evidence for a tight coupling between
      both lips in line with predictions from coordination dynamics accounts in the
      literature. 

PMID- 24686493
TI  - Protective effects of parental monitoring of children's media use: a prospective
      study.
AB  - IMPORTANCE: Children spend more time with electronic media than they do in any
      other activity, aside from sleep. Many of the negative effects that stem from
      media exposure may be reduced by parental monitoring of children's media use;
      however, there lacks a clear understanding of the mechanisms and extent of these
      protective effects. OBJECTIVE: To determine the prospective effects of parental
      monitoring of children's media on physical, social, and academic outcomes.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort design. Data were collected
      by in-home and in-school surveys in 2 communities in Iowa and Minnesota, where
      1323 third- (n = 430), fourth- (n = 446), and fifth- (n = 423) grade students
      participated. A primary caregiver and teachers also provided data about the
      student. INTERVENTIONS: Participants in the current study were recruited to
      participate in a social ecological model-based obesity prevention program. MAIN
      OUTCOMES AND MEASURES: Body mass index, average weekly sleep, school performance,
      prosocial behavior, and aggressive behavior. RESULTS Structural equation modeling
      revealed that parental monitoring of children's media influences children's
      sleep, school performance, and prosocial and aggressive behaviors and that these
      effects are mediated through total screen time and exposure to media violence.
      CONCLUSIONS AND RELEVANCE: Parental monitoring of media has protective effects on
      a wide variety of academic, social, and physical child outcomes. Pediatricians
      and physicians are uniquely positioned to provide scientifically based
      recommendations to families; encouraging parents to monitor children's media
      carefully can have a wide range of health benefits for children.

PMID- 24686494
TI  - Effortful pitch glide: a potential new exercise evaluated by dynamic MRI.
AB  - PURPOSE: The purpose of this study was to compare the biomechanics of the
      effortful pitch glide (EPG) with swallowing using dynamic MRI. The EPG is a
      combination of a pitch glide and a pharyngeal squeeze maneuver for targeting
      laryngeal and pharyngeal muscles. The authors hypothesized that the EPG would
      elicit significantly greater structural excursions of anterior hyoid, superior
      hyoid, hyolaryngeal approximation, laryngeal elevation, and lateral pharyngeal
      wall medialization compared with swallowing. METHOD: Eleven healthy, young
      subjects with a mean age of 25 were recruited. The EPG was first taught and
      verified via laryngoscopy. Then 2-planar (coronal and sagittal) dynamic MRI
      acquisitions captured 10 repeated swallows and 3 EPGs. Kinematic analyses of
      minimum and maximum excursion of anatomical landmarks were calculated. RESULTS:
      Results showed a nonsignificant difference between the 2 tasks for range of
      excursion with all measured biomechanics except for superior hyoid, where the
      swallow showed significantly greater excursion. This indicated that swallowing
      and EPG biomechanics were comparable, lending support for the potential use of
      the EPG as another nonswallowing exercise. CONCLUSION: Findings suggest EPG may
      be an effective exercise to target several important swallowing muscles,
      especially the long pharyngeal muscles that elevate the larynx and shorten the
      pharynx in swallowing.

PMID- 24686496
TI  - Spatiotemporal analysis of high-speed videolaryngoscopic imaging of organic
      pathologies in males.
AB  - PURPOSE: The aim of this study was to identify parameters that would
      differentiate healthy from pathological organic-based vocal fold vibrations to
      emphasize clinical usefulness of high-speed imaging. METHOD: Fifty-five men (M
      age = 36 years, SD = 20 years) were examined and separated into 4 groups: 1
      healthy (26 individuals) and 3 pathological (10 individuals with contact
      granuloma, 12 with polyps, and 7 with cysts). Vocal fold vibrations were recorded
      using a high-speed camera during sustained phonation. Twenty objective glottal
      area waveform and 24 phonovibrogram parameters representing spatiotemporal
      characteristics were analyzed. Statistical group comparisons were performed to
      document spatiotemporal changes for organic lesions that cannot be determined
      visually. To look for specific pattern profiles within organic lesions, the
      authors performed linear discriminant analysis. RESULTS: Thirteen parameters
      showed significant differences between the healthy group and at least 1
      pathological group. The differences occurred more in temporal than in spatial
      parameters. Contact granuloma showed the fewest statistical differences (3
      parameters), followed by cysts (9 parameters), and polyps (10 parameters). Linear
      discriminant analysis achieved accuracy performance of 76% (all groups separated)
      and 82% (healthy vs. pathological). CONCLUSION: The results suggest that for
      males, the differences between healthy voices and organic voice disorders may be
      more pronounced within temporal characteristics that cannot be visually detected
      without high-speed imaging.

PMID- 24686497
TI  - [Risk factors and prognosis of emergency cesarean delivery at the Yaounde Women's
      and Children's Hospital, Cameroon].
AB  - OBJECTIVE: To identify the risk factors for emergency cesarean deliveries and
      assess the effects of the emergency situation on maternal and fetal prognosis.
      METHODS: This retrospective cohort study compared emergency and elective cesarean
      deliveries performed at the Yaounde Women's and Children's Hospital in Cameroon,
      analyzing socioeconomic variables, the indications for surgery, and complications
      for mother and child. RESULTS: Risk factors predisposing to emergency cesareans
      were: age <20 years, not having a salaried job, unmarried status, no university
      level education, referral from other health facilities, primiparity, prenatal
      care in a health center or in a district hospital, prenatal care by a nurse, and
      preadmission rupture of membranes. Emergency cesareans increased the mothers risk
      of general anesthesia, unavailability of standard preoperative work-up during
      surgery, infection, and a longer hospital stay. Babies born by emergency cesarean
      delivery had a higher risk of admission to the neonatology unit, neonatal
      asphyxia, neonatal infection, preterm birth, and perinatal death. CONCLUSION: In
      our setting, lack of reproductive experience (primiparity), low socioeconomic
      level, poor prenatal care, and preadmission rupture of membranes were risk
      factors for emergency cesarean deliveries. The emergency situation exposes mother
      and child to a significant risk of morbidity and mortality.

PMID- 24686495
TI  - A new approach for the comparative analysis of multiprotein complexes based on
      15N metabolic labeling and quantitative mass spectrometry.
AB  - The introduced protocol provides a tool for the analysis of multiprotein
      complexes in the thylakoid membrane, by revealing insights into complex
      composition under different conditions. In this protocol the approach is
      demonstrated by comparing the composition of the protein complex responsible for
      cyclic electron flow (CEF) in Chlamydomonas reinhardtii, isolated from
      genetically different strains. The procedure comprises the isolation of thylakoid
      membranes, followed by their separation into multiprotein complexes by sucrose
      density gradient centrifugation, SDS-PAGE, immunodetection and comparative,
      quantitative mass spectrometry (MS) based on differential metabolic labeling
      ((14)N/(15)N) of the analyzed strains. Detergent solubilized thylakoid membranes
      are loaded on sucrose density gradients at equal chlorophyll concentration. After
      ultracentrifugation, the gradients are separated into fractions, which are
      analyzed by mass-spectrometry based on equal volume. This approach allows the
      investigation of the composition within the gradient fractions and moreover to
      analyze the migration behavior of different proteins, especially focusing on
      ANR1, CAS, and PGRL1. Furthermore, this method is demonstrated by confirming the
      results with immunoblotting and additionally by supporting the findings from
      previous studies (the identification and PSI-dependent migration of proteins that
      were previously described to be part of the CEF-supercomplex such as PGRL1, FNR,
      and cyt f). Notably, this approach is applicable to address a broad range of
      questions for which this protocol can be adopted and e.g. used for comparative
      analyses of multiprotein complex composition isolated from distinct environmental
      conditions. 

PMID- 24686498
TI  - Anti-inflammatory effect and prostate gene expression profiling of steryl
      ferulate on experimental rats with non-bacterial prostatitis.
AB  - Steryl ferulate (SF) is a bioactive mixture extracted from rice bran and shows
      higher inhibitory activity against inflammation than the corresponding free
      sterols. In this study, the aim was to investigate the anti-inflammatory effect
      and prostate gene expression profiling of SF using a Xiaozhiling-induced non
      bacterial prostatitis (NBP) rat model. The anti-inflammatory effect was evaluated
      by prostate weight, prostate index, acid phosphatase, density of lecithin
      corpuscles (DLC), white blood cell count (WBC), and prostatic histologic section.
      Prostate gene expression profiling was assessed by a cDNA microarray and
      validated by quantitative real-time PCR of five selected genes. Pathway analysis
      and Gene ontology (GO) analysis were applied to determine the roles of these
      differentially expressed genes involved in these biological pathways or GO terms.
      SF treatment could significantly inhibit prostate weight, prostate index, total
      acid phosphatase, prostatic acid phosphatase and WBC, suppress the severity of
      histological lesion and increase the DLC. Compared with the control group, the SF
      treatment group contained 238 up-regulated genes and 111 down-regulated genes. GO
      analysis demonstrated that the most significant expression genes were closely
      related to the terms of fibrinolysis, inflammatory response, high-density
      lipoprotein particle, protein-lipid complex, enzyme inhibitor activity, peptidase
      inhibitor activity and others. Canonical pathway analysis indicated five pathways
      were significantly regulated, which were associated with inflammation and
      tumorgenesis. In conclusion, SF may be used as a health supplement to prevent
      NBP, in that it could inhibit prostate inflammation in NBP patients by affecting
      the expression of genes in the related GO terms and pathways. 

PMID- 24686501
TI  - Affinity-based isolation of tagged nuclei from Drosophila tissues for gene
      expression analysis.
AB  - Drosophila melanogaster embryonic and larval tissues often contain a highly
      heterogeneous mixture of cell types, which can complicate the analysis of gene
      expression in these tissues. Thus, to analyze cell-specific gene expression
      profiles from Drosophila tissues, it may be necessary to isolate specific cell
      types with high purity and at sufficient yields for downstream applications such
      as transcriptional profiling and chromatin immunoprecipitation. However, the
      irregular cellular morphology in tissues such as the central nervous system,
      coupled with the rare population of specific cell types in these tissues, can
      pose challenges for traditional methods of cell isolation such as laser
      microdissection and fluorescence-activated cell sorting (FACS). Here, an
      alternative approach to characterizing cell-specific gene expression profiles
      using affinity-based isolation of tagged nuclei, rather than whole cells, is
      described. Nuclei in the specific cell type of interest are genetically labeled
      with a nuclear envelope-localized EGFP tag using the Gal4/UAS binary expression
      system. These EGFP-tagged nuclei can be isolated using antibodies against GFP
      that are coupled to magnetic beads. The approach described in this protocol
      enables consistent isolation of nuclei from specific cell types in the Drosophila
      larval central nervous system at high purity and at sufficient levels for
      expression analysis, even when these cell types comprise less than 2% of the
      total cell population in the tissue. This approach can be used to isolate nuclei
      from a wide variety of Drosophila embryonic and larval cell types using specific
      Gal4 drivers, and may be useful for isolating nuclei from cell types that are not
      suitable for FACS or laser microdissection. 

PMID- 24686499
TI  - Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell
      survival.
AB  - Sustained cellular function and viability of high-energy demanding post-mitotic
      cells rely on the continuous supply of ATP. The utilization of mitochondrial
      oxidative phosphorylation for efficient ATP generation is a function of oxygen
      levels. As such, oxygen deprivation, in physiological or pathological settings,
      has profound effects on cell metabolism and survival. Here we show that mild
      extracellular acidosis, a physiological consequence of anaerobic metabolism, can
      reprogramme the mitochondrial metabolic pathway to preserve efficient ATP
      production regardless of oxygen levels. Acidosis initiates a rapid and reversible
      homeostatic programme that restructures mitochondria, by regulating mitochondrial
      dynamics and cristae architecture, to reconfigure mitochondrial efficiency,
      maintain mitochondrial function and cell survival. Preventing mitochondrial
      remodelling results in mitochondrial dysfunction, fragmentation and cell death.
      Our findings challenge the notion that oxygen availability is a key limiting
      factor in oxidative metabolism and brings forth the concept that mitochondrial
      morphology can dictate the bioenergetic status of post-mitotic cells. 

PMID- 24686502
TI  - A demonstration of improved precision of word recognition scores.
AB  - PURPOSE The purpose of this study was to demonstrate improved precision of word
      recognition scores (WRSs) by increasing list length and analyzing phonemic
      errors. METHOD Pure-tone thresholds (frequencies between 0.25 and 8.0 kHz) and
      WRSs were measured in 3 levels of speech-shaped noise (50, 52, and 54 dB HL) for
      24 listeners with normal hearing. WRSs were obtained for half-lists and full
      lists of Northwestern University Test No. 6 (Tillman & Carhart, 1966) words
      presented at 48 dB HL. A resampling procedure was used to derive dimensionless
      effect sizes for identifying a change in hearing using the data. This allowed the
      direct comparison of the magnitude of shifts in WRS (%) and in the average pure
      tone threshold (dB), which provided a context for interpreting the WRS. RESULTS
      WRSs based on a 50-word list analyzed by the percentage of correct phonemes were
      significantly more sensitive for identifying a change in hearing than the WRSs
      based on 25-word lists analyzed by percentage of correct words. CONCLUSION
      Increasing the number of items that contribute to a WRS significantly increased
      the test's ability to identify a change in hearing. Clinical and research
      applications could potentially benefit from a more precise word recognition test,
      the only basic audiologic measure that estimates directly the distortion
      component of hearing loss and its effect on communication. 

PMID- 24686503
TI  - Effect of strain on voltage-controlled magnetism in BiFeO3-based
      heterostructures.
AB  - Voltage-modulated magnetism in magnetic/BiFeO3 heterostructures can be driven by
      a combination of the intrinsic ferroelectric-antiferromagnetic coupling in BiFeO3
      and the antiferromagnetic-ferromagnetic exchange interaction across the
      heterointerface. However, ferroelectric BiFeO3 film is also ferroelastic, thus it
      is possible to generate voltage-induced strain in BiFeO3 that could be applied
      onto the magnetic layer across the heterointerface and modulate magnetism through
      magnetoelastic coupling. Here, we investigated, using phase-field simulations,
      the role of strain in voltage-controlled magnetism for these BiFeO3-based
      heterostructures. It is predicted, under certain condition, coexistence of strain
      and exchange interaction will result in a pure voltage-driven 180 degrees 
      magnetization reversal in BiFeO3-based heterostructures. 

PMID- 24686505
TI  - Digit speech recognition threshold (SRT) in children with normal hearing ages 5-8
      years.
AB  - PURPOSE: The purpose of this study was to compare digit stimuli to popular
      spondees when measuring speech recognition threshold (SRT) in children with
      normal hearing and to determine the influence of increment size using a
      descending method (ASHA, 1988). METHOD: SRT was measured with paired digit
      stimuli (D-SRT) and pediatric word stimuli (W-SRT) using 2 step sizes (5 dB, 2
      dB) in 30 typically developing children with normal hearing ages 5;0
      (years;months) to 8;11. Pure-tone and SRT tests were administered in both ears.
      The D-SRT and W-SRT were compared to pure-tone average (PTA) thresholds per ear.
      RESULTS: Analysis of variance revealed a significant interaction of test and step
      size: PTA was significantly lower when measured with 2-dB than with 5-dB
      increment; however, step size yielded no differences in D-SRT and W-SRT. Right
      ear thresholds across tests were significantly lower than left ear. Pearson
      correlations were significant for all tests except two; D-SRT was highly
      correlated to W-SRT (r = .49-.72) in both ears. Regression analyses for both ears
      and step sizes revealed that prediction of the hearing threshold for speech from
      PTA was equally accurate for SRT measured with digit pairs or popular pediatric
      spondee stimuli. CONCLUSION: Digit pairs are an appropriate alternative stimulus
      for SRT measurement in children with normal hearing. Future diagnostic audiology
      implications, including application for other pediatric populations, are
      discussed.

PMID- 24686506
TI  - Validating models of clinical word recognition tests for spanish/english
      bilinguals.
AB  - PURPOSE: Shi and Sanchez (2010) developed models to predict the optimal test
      language for evaluating Spanish/English (S/E) bilinguals' word recognition. The
      current study intended to validate their conclusions in a separate bilingual
      listener sample. METHOD: Seventy normal-hearing S/E bilinguals varying in
      language profile were included. Participants were presented with English
      monosyllabic and Spanish bisyllabic words in quiet and in speech-spectrum noise
      (+6 and 0 dB SNR). Relative success on the 2 tests was indicated by the
      difference in z score for each test. RESULTS: The current group of participants
      was comparable to participants in Shi and Sanchez (2010) in regard to their
      language background and test performance. Previously developed models fit current
      data well. Age of English acquisition (AOAE) yielded more consistent models
      across test conditions than language dominance (LD). New models incorporating
      average proficiency rating (across domains) and relative proficiency rating
      (across languages) yielded best prediction. CONCLUSIONS: Shi and Sanchez's (2010)
      models incorporating key linguistic variables (AOAE, LD, and average/relative
      proficiency ratings) can help clinicians predict bilingual clients' relative
      success in word recognition in Spanish versus English. These models are
      appropriate for current clinical work with S/E bilinguals in metropolitan areas
      similar to New York City.

PMID- 24686507
TI  - Osteoarthritis pain: nociceptive or neuropathic?
AB  - In this article, we present the case for the existence of a subgroup of patients
      with osteoarthritis (OA) who experience pain with neuropathic features.
      Recognizing these patients as a distinct subgroup will allow clinicians to
      improve the management of their symptoms. We discuss the diagnostic criteria for
      pain to be classed as neuropathic, then systematically examine the applicability
      of these criteria to the symptoms, signs and pathology of OA. What are the
      implications for the preclinical development and clinical use of analgesics for
      OA? How should existing treatment options be reassessed? Differences in the
      aetiology of OA and the pharmacological sensitivity of patients with OA pain with
      neuropathic features, compared with other patients with OA, might explain the
      frequent negative findings of clinical trials of treatments for symptomatic OA.
      If the global prevalence of OA pain with neuropathic features is accurately
      represented by reports from small experimental groups of patients, then a
      substantial unmet need to tailor diagnosis and therapy for these individuals
      exists.

PMID- 24686508
TI  - Rheumatoid arthritis: ETA and MTX versus MTX alone in early inflammatory
      arthritis.

PMID- 24686509
TI  - Experimental arthritis: Antibody against CSF-1 receptor protects bone and
      cartilage.

PMID- 24686511
TI  - Speech compensation for time-scale-modified auditory feedback.
AB  - PURPOSE The purpose of this study was to examine speech compensation in response
      to time-scale-modified auditory feedback during the transition of the semivowel
      for a target utterance of /ija/. METHOD Each utterance session consisted of 10
      control trials in the normal feedback condition followed by 20 perturbed trials
      in the modified auditory feedback condition and 10 return trials in the normal
      feedback condition. The authors examined speech compensation and the aftereffect
      in terms of 3 acoustic features: the maximum velocities on the (a) F1 and (b) F2
      trajectories (VF1 and VF2) and (c) the F1-F2 onset time difference (TD) during
      the transition. They also conducted a syllable perception test on the feedback
      speech. RESULTS Speech compensation was observed in VF1, VF2, and TD. The
      magnitudes of speech compensation in VF1 and TD monotonically increased as the
      amount of the time-scale perturbation increased. The amount of speech
      compensation increased as the phonemic perception change increased. CONCLUSIONS
      Speech compensation for time-scale-modified auditory feedback is carried out
      primarily by changing VF1 and secondarily by adjusting VF2 and TD. Furthermore,
      it is activated primarily by detecting the speed change in altered feedback
      speech and secondarily by detecting the phonemic categorical change. 

PMID- 24686510
TI  - Selection bias in rheumatic disease research.
AB  - The identification of modifiable risk factors for the development of rheumatic
      conditions and their sequelae is crucial for reducing the substantial worldwide
      burden of these diseases. However, the validity of such research can be
      threatened by sources of bias, including confounding, measurement and selection
      biases. In this Review, we discuss potentially major issues of selection bias--a
      type of bias frequently overshadowed by other bias and feasibility issues,
      despite being equally or more problematic--in key areas of rheumatic disease
      research. We present index event bias (a type of selection bias) as one of the
      potentially unifying reasons behind some unexpected findings, such as the 'risk
      factor paradox'--a phenomenon exemplified by the discrepant effects of certain
      risk factors on the development versus the progression of osteoarthritis (OA) or
      rheumatoid arthritis (RA). We also discuss potential selection biases owing to
      differential loss to follow-up in RA and OA research, as well as those due to the
      depletion of susceptibles (prevalent user bias) and immortal time bias. The
      lesson remains that selection bias can be ubiquitous and, therefore, has the
      potential to lead the field astray. Thus, we conclude with suggestions to help
      investigators avoid such issues and limit the impact on future rheumatology
      research.

PMID- 24686512
TI  - Elucidating proline dynamics in spider dragline silk fibre using 2H-13C HETCOR
      MAS NMR.
AB  - (2)H-(13)C HETCOR MAS NMR is performed on (2)H/(13)C/(15)N-Pro enriched A.
      aurantia dragline silk. Proline dynamics are extracted from (2)H NMR line shapes
      and T1 in a site-specific manner to elucidate the backbone and side chain
      molecular dynamics for the MaSp2 GPGXX beta-turn regions for spider dragline silk
      in the dry and wet, supercontracted states. 

PMID- 24686513
TI  - Improving therapist fidelity during implementation of evidence-based practices:
      Incredible years program.
AB  - OBJECTIVE: The aim of the study was to extend research on the potential benefits
      of adding ongoing feedback, coaching, and consultation to initial therapist
      training workshops to ensure fidelity of delivery of evidence-based practices,
      specifically for the Incredible Years parenting program. METHODS: A randomized
      controlled trial compared two models for training therapists to deliver the
      parenting program for children at high risk of developing conduct problems.
      Therapists (N=56) from ten community-based mental health service organizations in
      California were trained in either a three-day workshop model (N=25), based on
      active, experiential, self-reflective, principle-based learning, video modeling,
      and manuals, or an enhanced training model (N=31) that included all elements of
      the workshop model plus ongoing expert coaching, video review of and feedback on
      group sessions, and consultation for therapists and agency supervisors. RESULTS:
      Overall fidelity across both conditions was rated >3 on a 5-point scale in seven
      of eight domains measured. Therapists in the condition that received ongoing
      coaching and consultation were significantly stronger in four of the domains:
      practical support, collaboration, knowledge, and skill at mediating vignettes.
      CONCLUSIONS: Consultation and expert coaching for training therapists beyond the
      standard three-day training enhanced skills and therapists' adherence to the
      model.

PMID- 24686514
TI  - Signal transduction of platelet-induced liver regeneration and decrease of liver
      fibrosis.
AB  - Platelets contain three types of granules: alpha granules, dense granules, and
      lysosomal granules. Each granule contains various growth factors, cytokines, and
      other physiological substances. Platelets trigger many kinds of biological
      responses, such as hemostasis, wound healing, and tissue regeneration. This
      review presents experimental evidence of platelets in accelerating liver
      regeneration and improving liver fibrosis. The regenerative effect of liver by
      platelets consists of three mechanisms; i.e., the direct effect on hepatocytes,
      the cooperative effect with liver sinusoidal endothelial cells, and the
      collaborative effect with Kupffer cells. Many signal transduction pathways are
      involved in hepatocyte proliferation. One is activation of Akt and extracellular
      signal-regulated kinase (ERK)1/2, which are derived from direct stimulation from
      growth factors in platelets. The other is signal transducer and activator of
      transcription-3 (STAT3) activation by interleukin (IL)-6 derived from liver
      sinusoidal endothelial cells and Kupffer cells, which are stimulated by contact
      with platelets during liver regeneration. Platelets also improve liver fibrosis
      in rodent models by inactivating hepatic stellate cells to decrease collagen
      production. The level of intracellular cyclic adenosine monophosphate (cyclic
      AMP) is increased by adenosine through its receptors on hepatic stellate cells,
      resulting in inactivation of these cells. Adenosine is produced by the
      degradation of adenine nucleotides such as adenosine diphosphate (ADP) and
      adenosine tri-phosphate (ATP), which are stored in abundance within the dense
      granules of platelets. 

PMID- 24686516
TI  - CHRNA3 polymorphism modifies lung adenocarcinoma risk in the Chinese Han
      population.
AB  - Recent genome-wide association studies (GWASs) have identified 15q25.1 as a lung
      cancer susceptibility locus. Here, we sought to explore the direct carcinogenic
      effects of genetic variants in this region on the risk of developing lung
      adenocarcinoma (ADC). Five common SNPs (rs8034191, rs16969968, rs1051730,
      rs938682, and rs8042374) spanning the 15q25.1 locus were assayed in a case
      control study examining a cohort of 301 lung ADCs and 318 healthy controls.
      Stratification analysis by gender, smoking status, and tumor, node, metastasis
      (TNM) classification, was performed. In addition, sections from ADC tissue and
      normal tissue adjacent to tumors were stained with an anti-CHRNA3 (cholinergic
      receptor nicotinic alpha3) antibody by immunohistochemistry in 81 cases. Our
      results demonstrate that rs8042374, a variant of the CHRNA3 gene, is associated
      with an increased risk of ADC with an OR of 1.76 (95% CI: 1.17-2.65, p=0.024).
      This variant was linked to a greater risk of ADC in female nonsmokers (OR (95%
      CI): 1.81 (1.05-3.12), p=0.032) and female stage I+II cases (OR (95% CI): 1.92
      (1.03-3.57), p=0.039). Although located within the same gene, rs938682 showed
      protective effects for smokers, stage III+IV cases, and male stage III+IV cases.
      Additionally, the CHRNA3 protein level in ADC tissue was slightly higher than in
      the surrounding normal lung tissue, based on immunohistochemical analysis. Our
      results suggest that the CHRNA3 polymorphism functions as a genetic modifier of
      the risk of developing lung ADC in the Chinese population, particularly in
      nonsmoking females.

PMID- 24686515
TI  - Current strategies to improve the bioactivity of PEEK.
AB  - The synthetic thermoplastic polymer polyetheretherketone (PEEK) is becoming a
      popular component of clinical orthopedic and spinal applications, but its
      practical use suffers from several limitations. Although PEEK is biocompatible,
      chemically stable, radiolucent and has an elastic modulus similar to that of
      normal human bone, it is biologically inert, preventing good integration with
      adjacent bone tissues upon implantation. Recent efforts have focused on
      increasing the bioactivity of PEEK to improve the bone-implant interface. Two
      main strategies have been used to overcome the inert character of PEEK. One
      approach is surface modification to activate PEEK through surface treatment alone
      or in combination with a surface coating. Another strategy is to prepare
      bioactive PEEK composites by impregnating bioactive materials into PEEK
      substrate. Researchers believe that modified bioactive PEEK will have a wide
      range of orthopedic applications. 

PMID- 24686517
TI  - Oral administration of bovine milk from cows hyperimmunized with intestinal
      bacterin stimulates lamina propria T lymphocytes to produce Th1-biased cytokines
      in mice.
AB  - The goal of this study was to examine the effects of oral administration of
      bovine milk from cows hyperimmunized with a proprietary bacterin (immune milk
      "Sustaina") on mucosal immunity in the intestine of adult mice. C57BL/6 mice were
      orally given immune or control milk for two weeks, and then lymphocyte population
      and the cytokine production in lamina propria of colon in normal mice and mice
      induced colitis by dextran sulphate sodium (DSS) were detected. We found that the
      levels of IFN-gamma and IL-10 increased, but the levels of IL-17A and IL-4,
      decreased in lamina propria of colon in immune milk-fed mice as compared with
      those in control milk-fed mice. Interestingly, oral administration of immune milk
      partially improved the acute colitis induced by DSS. The levels of TNF-alpha and
      IFN-gamma increased, but IL-6, IL-17A and IL-4 decreased in lamina propria (LP)
      of colon in immune milk-fed mice with DSS-induced colitis. Our results suggest
      that immune milk may stimulate CD4+ T cells to polarize towards a Th1 type
      response, but contrarily suppress Th17 and Th2 cells responses in large
      intestinal LP of mice. The results indicate that this kind of immune milk has is
      able to promote the maintainance of intestinal homeostasis and enhance protection
      against infection, and could alleviate the symptoms of acute colitis in mice. 

PMID- 24686519
TI  - Address of the president, Paul Nurse, given at the Anniversary meeting on 30
      November 2012.

PMID- 24686518
TI  - Effect of Wnt3a on keratinocytes utilizing in vitro and bioinformatics analysis.
AB  - Wingless-type (Wnt) signaling proteins participate in various cell developmental
      processes. A suppressive role of Wnt5a on keratinocyte growth has already been
      observed. However, the role of other Wnt proteins in proliferation and
      differentiation of keratinocytes remains unknown. Here, we investigated the
      effects of the Wnt ligand, Wnt3a, on proliferation and differentiation of
      keratinocytes. Keratinocytes from normal human skin were cultured and treated
      with recombinant Wnt3a alone or in combination with the inflammatory cytokine,
      tumor necrosis factor alpha (TNFalpha). Furthermore, using bioinformatics, we
      analyzed the biochemical parameters, molecular evolution, and protein-protein
      interaction network for the Wnt family. Application of recombinant Wnt3a showed
      an anti-proliferative effect on keratinocytes in a dose-dependent manner. After
      treatment with TNFalpha, Wnt3a still demonstrated an anti-proliferative effect on
      human keratinocytes. Exogenous treatment of Wnt3a was unable to alter mRNA
      expression of differentiation markers of keratinocytes, whereas an altered
      expression was observed in TNFalpha-stimulated keratinocytes. In silico
      phylogenetic, biochemical, and protein-protein interaction analysis showed
      several close relationships among the family members of the Wnt family. Moreover,
      a close phylogenetic and biochemical similarity was observed between Wnt3a and
      Wnt5a. Finally, we proposed a hypothetical mechanism to illustrate how the Wnt3a
      protein may inhibit the process of proliferation in keratinocytes, which would be
      useful for future researchers. 

PMID- 24686520
TI  - The effects of indexical and phonetic variation on vowel perception in typically
      developing 9- to 12-year-old children.
AB  - PURPOSE The purpose of this study was to investigate how linguistic knowledge
      interacts with indexical knowledge in older children's perception under demanding
      listening conditions created by extensive talker variability. METHOD Twenty-five
      9- to 12-year-old children, 12 from North Carolina (NC) and 13 from Wisconsin
      (WI), identified 12 vowels in isolated /hVd/ words produced by 120 talkers
      representing the 2 dialects (NC and WI), both genders, and 3 age groups
      (generations) of residents from the same geographic locations as the listeners.
      RESULTS Identification rates were higher for responses to talkers from the same
      dialect as the listeners and for female speech. Listeners were sensitive to
      systematic positional variations in vowels and their dynamic structure (formant
      movement) associated with generational differences in vowel pronunciation
      resulting from sound change in a speech community. Overall identification rate
      was 71.7%, which is 8.5% lower than for the adults responding to the same stimuli
      in Jacewicz and Fox (2012). CONCLUSION Typically developing older children were
      successful in dealing with both phonetic and indexical variation related to
      talker dialect, gender, and generation. They were less consistent than the
      adults, most likely because of less efficient encoding of acoustic-phonetic
      information in the speech of multiple talkers and relative inexperience with
      indexical variation. 

PMID- 24686521
TI  - Mechanisms of airway protection during chin-down swallowing.
AB  - PURPOSE: This study examined the effects of chin-down swallowing on laryngeal
      vestibule closure. It also investigated the technique's rehabilitative impact, by
      assessing the stability of effects across multiple trials and aftereffects in
      neutral swallows on cessation of the technique. METHOD: Duration of laryngeal
      vestibule closure (dLVC) was measured with videofluoroscopy in 16 healthy
      participants (mean = 33.2 years, 9 men). Participants swallowed 40 times: 5 head
      neutral swallows (N1), then 30 chin-down swallows, followed by 5 head-neutral
      swallows (N2). The first 5 chin-down swallows were categorized as early posture
      swallows (P1) and the last 5 as late posture swallows (P2). Within-participant
      comparisons determined the effects of the maneuver on dLVC during and after
      execution. RESULTS: The study found that dLVC increased during chin-down swallows
      (N1 to P1, p = .018). This increase remained stable throughout 30 repetitions (P1
      to P2, p = .994). On return to neutral, dLVC returned to baseline (N1 to N2, p =
      .875). CONCLUSIONS: This study demonstrated increased dLVC during chin-down
      swallowing, offering a possible mechanism responsible for previously reported
      reduced aspiration during the technique. As aftereffects were not evident after
      multiple chin-down swallows, the maneuver appears to offer more compensatory
      benefit than rehabilitative value for patients with dysphagia.

PMID- 24686522
TI  - Reliability of an automated high-resolution manometry analysis program across
      expert users, novice users, and speech-language pathologists.
AB  - PURPOSE: The purpose of this study was to investigate inter- and intrarater
      reliability among expert users, novice users, and speech-language pathologists
      with a semiautomated high-resolution manometry analysis program. We hypothesized
      that all users would have high intrarater reliability and high interrater
      reliability. METHOD: Three expert users, 15 novice users, and 5 speech-language
      pathologists participated in this study. Following a 20-min training session,
      users analyzed 30 high-resolution manometry plots using an automated analysis
      program. Output parameters included 2- and 3-dimensional pressure integrals over
      5 anatomical regions of interest. Intraclass correlations were used to examine
      inter- and intrarater reliability. An analysis of variance was also performed to
      determine any differences in mean output parameter values. RESULTS: Within-group
      interrater reliability ranged from 0.54 to 0.99, and intergroup reliability
      ranged from 0.92 to 0.99. Intrarater reliability ranged from 0.67 to 1.00 across
      all groups. There were no significant differences of output parameters among
      groups. CONCLUSIONS: The high reliability observed after a short training session
      demonstrates that individuals with little to no prior knowledge of swallowing
      physiology can perform at a similar level as those with expertise. Given the
      quickness and ease of training in the use of this program, it has the potential
      for research and clinical utility.

PMID- 24686523
TI  - Imaging cell membrane injury and subcellular processes involved in repair.
AB  - The ability of injured cells to heal is a fundamental cellular process, but
      cellular and molecular mechanisms involved in healing injured cells are poorly
      understood. Here assays are described to monitor the ability and kinetics of
      healing of cultured cells following localized injury. The first protocol
      describes an end point based approach to simultaneously assess cell membrane
      repair ability of hundreds of cells. The second protocol describes a real time
      imaging approach to monitor the kinetics of cell membrane repair in individual
      cells following localized injury with a pulsed laser. As healing injured cells
      involves trafficking of specific proteins and subcellular compartments to the
      site of injury, the third protocol describes the use of above end point based
      approach to assess one such trafficking event (lysosomal exocytosis) in hundreds
      of cells injured simultaneously and the last protocol describes the use of pulsed
      laser injury together with TIRF microscopy to monitor the dynamics of individual
      subcellular compartments in injured cells at high spatial and temporal
      resolution. While the protocols here describe the use of these approaches to
      study the link between cell membrane repair and lysosomal exocytosis in cultured
      muscle cells, they can be applied as such for any other adherent cultured cell
      and subcellular compartment of choice. 

PMID- 24686525
TI  - Prostate cancer: MRI reduces low-risk prostate cancer diagnosis and biopsy.

PMID- 24686530
TI  - A ratiometric fluorescent probe for the detection of hydroxyl radicals in living
      cells.
AB  - A naphthalimide-naphthyridine derivative has been synthesized for the detection
      of hydroxyl radicals. It can distinguish hydroxyl radicals from other reactive
      oxygen species with high selectivity and short response time. Moreover, it has no
      cellular toxicity, and can be effectively used for intracellular detection of
      hydroxyl radicals. 

PMID- 24686526
TI  - Immune mediators of chronic pelvic pain syndrome.
AB  - The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since
      the late 1980s, cytokine, chemokine, and immunological classification studies
      using human samples have focused on identifying biomarkers for CPPS, but no
      diagnostically beneficial biomarkers have been identified, and these studies have
      done little to deepen our understanding of the mechanisms underlying chronic
      prostatic pain. Given the large number of men thought to be affected by this
      condition and the ineffective nature of current treatments, there is a pressing
      need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are
      classified according to the presence of pain without concurrent presence of
      bacteria; however, it is becoming more evident that, although levels of bacteria
      are not directly associated with levels of pain, the presence of bacteria might
      act as the initiating factor that drives primary activation of mast-cell-mediated
      inflammation in the prostate. Mast cell activation is also known to suppress
      regulatory T cell (Treg) control of self-tolerance and also activate neural
      sensitization. This combination of established autoimmunity coupled with
      peripheral and central neural sensitization can result in the development of
      multiple symptoms, including pelvic pain and bladder irritation. Identifying
      these mechanisms as central mediators in CPPS offers new insight into the
      prospective treatment of the disease. 

PMID- 24686531
TI  - [Qualitative analysis of palliative care and support in medical practices in
      DRC].
AB  - This work aims at documenting the representations that health professionals in
      Kinshasa have of palliative care and end-of-life support. This qualitative study
      was conducted among 30 doctors and 90 nurses with at least one year of experience
      in six hospitals in Kinshasa that receive patients at the end of life. The
      results show that health professionals believe that this care is time-consuming
      and that the inability to say some things to patients and families generates
      misunderstandings and concerns likely to prevent the application of palliative
      care. For them, it is often a futile therapeutic obstinacy, added hygienic care,
      and neglect of the patient. The obstacles to implementing this care might be
      linked to the lack of training about this approach and a health system based
      essentially on curative approaches. The representation of health professionals
      about palliative care and support are many and varied. They are, however, more
      structured among physicians than nurses. 

PMID- 24686532
TI  - Mizoroki-heck cross-coupling reactions catalyzed by dichloro{bis[1,1',1''
      (phosphinetriyl)tripiperidine]}palladium under mild reaction conditions.
AB  - Dichloro-bis(aminophosphine) complexes of palladium with the general formula of
      [(P{(NC5H10)3-n(C6H11)n})2Pd(Cl)2] (where n = 0-2), belong to a new family of
      easy accessible, very cheap, and air stable, but highly active and universally
      applicable C-C cross-coupling catalysts with an excellent functional group
      tolerance. Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium
      [(P(NC5H10)3)2Pd(Cl)2] (1), the least stable complex within this series towards
      protons; e.g. in the form of water, allows an eased nanoparticle formation and
      hence, proved to be the most active Heck catalyst within this series at 100 
      degrees C and is a very rare example of an effective and versatile catalyst
      system that efficiently operates under mild reaction conditions. Rapid and
      complete catalyst degradation under work-up conditions into phosphonates,
      piperidinium salts and other, palladium-containing decomposition products assure
      an easy separation of the coupling products from catalyst and ligands. The
      facile, cheap, and rapid synthesis of 1,1',1"-(phosphinetriyl)tripiperidine and 1
      respectively, the simple and convenient use as well as its excellent catalytic
      performance in the Heck reaction at 100  degrees C make 1 to one of the most
      attractive and greenest Heck catalysts available. We provide here the visualized
      protocols for the ligand and catalyst syntheses as well as the reaction protocol
      for Heck reactions performed at 10 mmol scale at 100  degrees C and show that
      this catalyst is suitable for its use in organic syntheses. 

PMID- 24686533
TI  - Morphological and functional remodelling of the neuromuscular junction by
      skeletal muscle PGC-1alpha.
AB  - The neuromuscular junction (NMJ) exhibits high morphological and functional
      plasticity. In the mature muscle, the relative levels of physical activity are
      the major determinants of NMJ function. Classically, motor neuron-mediated
      activation patterns of skeletal muscle have been thought of as the major drivers
      of NMJ plasticity and the ensuing fibre-type determination in muscle. Here we use
      muscle-specific transgenic animals for the peroxisome proliferator-activated
      receptor gamma co-activator 1alpha (PGC-1alpha) as a genetic model for trained
      mice to elucidate the contribution of skeletal muscle to activity-induced
      adaptation of the NMJ. We find that muscle-specific expression of PGC-1alpha
      promotes a remodelling of the NMJ, even in the absence of increased physical
      activity. Importantly, these plastic changes are not restricted to post-synaptic
      structures, but extended to modulation of presynaptic cell morphology and
      function. Therefore, our data indicate that skeletal muscle significantly
      contributes to the adaptation of the NMJ subsequent to physical activity. 

PMID- 24686535
TI  - Test-retest reliability of respiratory resistance measured with the airflow
      perturbation device.
AB  - PURPOSE: In this study, the authors aimed to determine reliability of the airflow
      perturbation device (APD) to measure respiratory resistance within and across
      sessions during resting tidal (RTB) and postexercise breathing in healthy
      athletes, and during RTB across trials within a session in athletes with
      paradoxical vocal fold motion (PVFM) disorder. METHOD: Prospective, repeated
      measures design. The APD measured respiratory resistance during 3 baseline
      assessments in 24 teenage female athletes, 12 with and 12 without PVFM. Control
      athletes provided data at rest and following a customized exercise challenge
      during each of 3 sessions. Intraclass correlation coefficient (ICC) analysis
      assessed strength of relationships, and repeated-measures analysis of variance
      assessed differences across trials and sessions. RESULTS: ICC analyses confirmed
      strong correlations across RTB trials for inspiratory, expiratory, and mean
      respiratory resistance in both groups. Inspiratory resistance decreased ~5%
      between sessions for control participants; expiratory and mean respiratory
      resistances were stable. Data from control athletes across sessions and following
      rigorous exercise were strongly correlated when taken at comparable intervals.
      CONCLUSIONS: APD-measured respiratory resistance, including separate assessments
      for the inspiratory and expiratory phases, has strong test-retest reliability
      during RTB and after exercising. This suggests that the APD is a useful
      measurement tool for the assessment of airway function in patients suspected of
      having PVFM.

PMID- 24686534
TI  - Xanthine oxidase inhibition by febuxostat attenuates experimental atherosclerosis
      in mice.
AB  - Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the
      arterial wall. Multiple mechanisms participate in the inflammatory process,
      including oxidative stress. Xanthine oxidase (XO) is a major source of reactive
      oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis,
      but the underlying mechanisms remain unclear. Here, we show enhanced XO
      expression in macrophages in the atherosclerotic plaque and in aortic endothelial
      cells in ApoE(-/-) mice, and that febuxostat, a highly potent XO inhibitor,
      suppressed plaque formation, reduced arterial ROS levels and improved endothelial
      dysfunction in ApoE(-/-) mice without affecting plasma cholesterol levels. In
      vitro, febuxostat inhibited cholesterol crystal-induced ROS formation and
      inflammatory cytokine release in murine macrophages. These results demonstrate
      that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory
      and XO-inhibition by febuxostat is a potential therapy for atherosclerosis. 

PMID- 24686536
TI  - Rapid in vitro protein synthesis pipeline: a promising tool for cost-effective
      protein array design.
AB  - Several protein expression systems for construction of protein arrays have been
      established in recent years. However, current protocols for protein synthesis are
      still time consuming, laborious and expensive. This study has established an
      alternative workflow that covers rapid construction of expression cassettes, in
      tube and on-membrane synthesis of recombinant proteins, and straightforward
      screening of synthesized proteins. Eighteen membrane associated eukaryotic
      proteins and two secretory complement regulators (C1 inhibitor and vitronectin)
      were included in the study. To generate hybrid genes, double-overlap extension
      PCR was employed to fuse the 5' fragment (consisting of a T7 promoter and a
      species independent translation sequence), ORFs of the target proteins, and the
      3' fragment (encompassing GFP fusion, Myc-tag and stop codon). OE-PCR generated
      fragments were directly mixed with the Leishmania torentolae lysate (translation
      mix) for protein synthesis. In order to establish a cheap and user-friendly
      alternative to existing cell-free protein array techniques, PCR products were
      spotted on the hydrophobic substrate (PVDF membrane), air-dried and covered with
      only 2 MUL of translation mix. All synthesized proteins were spontaneously
      immobilized on the membrane due to the hydrophobic interaction between C
      terminally fused GFP and PVDF. Synthesis and immobilization of proteins were
      confirmed simply by assessing the GFP chromophore under a laser scanner or a
      fluorescent microscope. 

PMID- 24686537
TI  - Effects of intensive phonomotor treatment on reading in eight individuals with
      aphasia and phonological alexia.
AB  - PURPOSE: The aim of this study was to investigate effects of a multimodal
      treatment of phonology, phonomotor treatment, on the reading abilities of persons
      with aphasia (PWA) with phonological alexia. METHOD: In a retrospective, single
      group design, this study presents pre-, post-, and 3-months posttreatment data
      for 8 PWA with phonological alexia. Participants completed 60 hr of phonomotor
      treatment over 6 weeks. Wilcoxon signed-ranks tests and group effect sizes
      comparing pre-, immediately post-, and 3-months posttreatment performance on
      tests of phonological processing and reading were performed. RESULTS: Group data
      showed phonological processing and oral reading of real words and nonwords
      improved significantly posttreatment; these gains were maintained 3 months later.
      No group improvement was found for reading comprehension; however, one individual
      did show improvement immediately post- and 3-months posttreatment. CONCLUSIONS:
      This study provides support that phonomotor treatment is a viable approach to
      improve phonological processing and oral reading for PWA with phonological
      alexia. The lack of improvement with comprehension is inconsistent with prior
      work using similar treatments (Conway et al., 1998; Kendall et al., 2003).
      However, this difference can, in part, be accounted for by differences in
      variables, such as treatment intensity and frequency, outcome measures, and
      alexia severity.

PMID- 24686539
TI  - China organ donation and transplantation update: the Hangzhou Resolution.

PMID- 24686538
TI  - Quality of follow-up after hospitalization for mental illness among patients from
      racial-ethnic minority groups.
AB  - OBJECTIVE: Outpatient follow-up after hospitalization for mental health reasons
      is an important indicator of quality of health systems. Differences among racial
      ethnic minority groups in the quality of service use during this period are
      understudied. This study assessed the quality of outpatient treatment episodes
      following inpatient psychiatric treatment among blacks, whites, and Latinos in
      the United States. METHODS: The Medical Expenditure Panel Survey (2004-2010) was
      used to identify adults with any inpatient psychiatric treatment (N=339).
      Logistic regression models were used to estimate predictors of any outpatient
      follow-up or the beginning of adequate outpatient follow-up within seven or 30
      days following discharge. Predicted disparities were calculated after adjustment
      for clinical need variables but not for socioeconomic characteristics, consistent
      with the Institute of Medicine definition of health care disparities as
      differences that are unrelated to clinical appropriateness, need, or patient
      preference. RESULTS: Rates of follow-up were generally low, particularly rates of
      adequate treatment (<26%). Outpatient treatment prior to inpatient care was a
      strong predictor of all measures of follow-up. After adjustment for need and
      socioeconomic status, the analyses showed that blacks were less likely than
      whites to receive any treatment or begin adequate follow-up within 30 days of
      discharge. CONCLUSIONS: Poor integration of follow-up treatment in the continuum
      of psychiatric care leaves many individuals, particularly blacks, with poor
      quality treatment. Culturally appropriate interventions that link individuals in
      inpatient settings to outpatient follow-up are needed to reduce racial-ethnic
      disparities in outpatient mental health treatment following acute treatment.

PMID- 24686540
TI  - Primary graft dysfunction after liver transplantation.
AB  - BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver
      transplantation, which result in poor prognosis. Recipients who develop PGD
      usually experience a longer intensive care unit and hospital stay and have higher
      mortality and graft loss rates compared with those without graft dysfunction.
      However, because of the lack of universally accepted definition, early diagnosis
      of graft dysfunction is difficult. Additionally, numerous factors affect the
      allograft function after transplantation, making the prediction of PGD more
      difficult. The present review was to analyze the literature available on PGD and
      to propose a definition. DATA SOURCE: A search of PubMed (up to the end of 2012)
      for English-language articles relevant to PGD was performed to clarify the
      characteristics, risk factors, and possible treatments or interventions for PGD.
      RESULTS: There is no pathological diagnostic standard; many documented
      definitions of PGD are different. Many factors, such as donor status, procurement
      and transplant process and recipient illness may affect the function of graft,
      and ischemia-reperfusion injury is considered the direct cause. Potential
      managements which are helpful to improve graft function were investigated. Some
      of them are promising. CONCLUSIONS: Our analyses suggested that the definition of
      PGD should include one or more of the following variables: (1) bilirubin >= 10
      mg/dL on postoperative day 7; (2) international normalized ratio >= 1.6 on
      postoperative day 7; and (3) alanine aminotransferase or aspartate
      aminotransferase >2000 IU/L within 7 postoperative days. Reducing risk factors
      may decrease the incidence of PGD. A majority of the recipients could recover
      from PGD; however, when the graft progresses into primary non-function, the
      patients need to be treated with re-transplantation.

PMID- 24686541
TI  - Inflammatory response of macrophages in infection.
AB  - BACKGROUND: Macrophages are widely-distributed innate immune cells playing
      diverse roles in various physiological and pathological processes. The primary
      function of macrophages is to phagocytize and clear invading pathogens. DATA
      SOURCES: A systematic search of PubMed was performed to identify relevant studies
      in English language literature using the key words such as macrophage and
      inflammation. A total of 122 articles related to inflammatory response of
      macrophages in infection were systematically reviewed. RESULTS: The inflammatory
      responses of macrophages triggered by infection comprise four interrelated
      phases: recognition of pathogen-associated molecular patterns by pattern
      recognition receptors expressed on/in macrophages; enrichment of quantity of
      macrophages in local infected tissue by recruitment of circulating monocytes
      and/or in situ proliferation; macrophage-mediation of microbicidal activity and
      conversion to anti-inflammatory phenotype to terminate anti-infectious response
      and to promote tissue repair. Complicated regulation of macrophage activation at
      molecular level recognized in the past decade is also reviewed, including
      intracellular multiple signaling molecules, membrane molecules, microRNAs and
      even epigenetic-associated molecules. CONCLUSION: The inflammatory response of
      macrophages in infection is an orderly and complicated process under elaborate
      regulation at molecular level.

PMID- 24686542
TI  - Risk factors associated with early and late recurrence after curative resection
      of hepatocellular carcinoma: a single institution's experience with 398
      consecutive patients.
AB  - BACKGROUND: Surgical resection is an important curative treatment for
      hepatocellular carcinoma (HCC); however, some patients experience an unexpected
      recurrence even after hepatectomy. The present study aimed to investigate risk
      factors and predictive criteria for early and late recurrence of HCC after
      resection. METHODS: A retrospective analysis of 398 Chinese patients who received
      curative resection for HCC was conducted. Patients were divided into three
      groups: without recurrence, early recurrence, and late recurrence. Prognostic
      factors and predictive criteria for early and late recurrence were statistically
      analyzed. RESULTS: The cumulative recurrence-free survival rates at 1, 2, 3, 4,
      and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and 28.7%, respectively. The
      distribution of the time to recurrence suggested that recurrence could be divided
      into early phase (before 2 years; n=164) and late phase (after 2 years; n=83).
      Cox's multivariate proportional hazard model analysis revealed that multiplicity
      of tumors (P=0.004) and venous infiltration (P=0.002) were independent risk
      factors associated with early recurrence. In contrast, indocyanine green
      retention rate at 15 minutes (P=0.007), serum albumin level (P=0.045), and HBeAg
      status (P=0.028) proved to be significant independent adverse prognostic factors
      for late recurrence. Patients with at least 1 of the 2 early recurrence risk
      factors (multiplicity of tumors >= 2 and venous infiltration) or with 2 or more
      late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and
      1.0e-6, respectively). CONCLUSIONS: Early and late recurrences correlate with
      different risk factors and predictive criteria. Early recurrence primarily
      results from intrahepatic metastases, while late recurrence may be multicentric
      in origin.

PMID- 24686543
TI  - Influence of hepatitis viruses on clinicopathological profiles and long-term
      outcome in patients undergoing surgery for hepatocellular carcinoma.
AB  - BACKGROUND: The global risk of hepatocellular carcinoma (HCC) is largely due to
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In recent years,
      however, an increased prevalence of non-viral HCC has been noted. The clinical
      impact of the presence/absence of viral infections in HCC remains controversial.
      The present study aimed to assess the effect of hepatitis viruses on
      demographics, clinical and pathological features and long-term outcome in a large
      cohort of Romanian patients who underwent surgery for HCC. METHODS: The study
      included 404 patients with HCC who had undergone resection, transplantation or
      radiofrequency ablation at a single institution between 2001 and 2010. The
      patients were divided into four groups: 85 patients with hepatitis B virus
      infection (HBV group), 164 patients with hepatitis C virus infection (HCV group),
      39 patients with hepatitis B and C virus co-infection (HBCV group), and 116
      patients without viral infection (non-BC group). RESULTS: The patients of both
      HBV (56.0+/-11.3 years) and HBCV groups (56.0+/-9.9 years) were significantly
      younger than those of the HCV (61.0+/-8.5 years, P=0.001) and non-BC groups
      (61.0+/-13.0 years, P=0.002). Interestingly, the prevalence of liver cirrhosis
      was significantly lower in the non-BC group (47%) than in any other subsets (72%
      90%, P<0.002). Furthermore, the non-BC patients were more advanced according to
      the Barcelona Clinic Liver Cancer stages than the patients of the HCV or HBCV
      groups (P<0.020); accordingly, they were more frequently assessed beyond the
      Milan criteria than any other groups (P=0.001). No significant differences in the
      disease-free or overall survival rates were observed among these groups.
      CONCLUSIONS: Patients with non-viral HCC are diagnosed at advanced ages and
      stages, a situation plausibly due to the poor effectiveness of cancer
      surveillance in community practice. The presence of viral infections does not
      appear to impair the long-term prognosis after surgical treatment in patients
      with HCC; however, there is a trend for worse disease-free survival rates in HBCV
      patients, though statistical significance was not reached.

PMID- 24686544
TI  - Angiographic embolization in the treatment of intrahepatic arterial bleeding in
      patients with blunt abdominal trauma.
AB  - BACKGROUND: Angiographic embolization (AE) as an adjunct non-operative treatment
      of intrahepatic arterial bleeding has been widely used. The present study aimed
      to evaluate the efficacy of selective AE in patients with hepatic trauma.
      METHODS: Seventy patients with intrahepatic arterial bleeding after blunt
      abdominal trauma who had undergone selective AE in 10 years at this institution
      were retrospectively reviewed. The criteria for selective AE included active
      extravasation on contrast-enhanced CT, an episode of hypotension or a decrease in
      hemoglobin level during the non-operative treatment. The data of the patients
      included demographics, grade of liver injuries, mechanism of blunt abdominal
      trauma, associated intra-abdominal injuries, indications for AE, angiographic
      findings, type of AE, and AE-related hepatobiliary complications. RESULTS: In the
      70 patients, 32 (45.71%) had high-grade liver injuries. Extravazation during the
      early arterial phase mainly involved the right hepatic segments. Thirteen
      (18.57%) patients underwent embolization of intrahepatic branches and the
      extrahepatic trunk and these patients all developed AE-related hepatobiliary
      complications. In 19 patients with AE-related complications, 14 received
      minimally invasive treatment and recovered without severe sequelae. CONCLUSIONS:
      AE is an adjunct treatment for liver injuries. Selective and/or super-selective
      AE should be advocated to decrease the incidence and severity of AE-related
      hepatobiliary complications.

PMID- 24686545
TI  - Effects of plasma exchange combined with continuous renal replacement therapy on
      acute fatty liver of pregnancy.
AB  - BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early
      postpartum period can lead to fatal liver damage. Its traditional therapy is not
      very effective in facilitating hepatic recovery. The safety and effect of plasma
      exchange (PE) in combination with continuous renal replacement therapy (CRRT)
      (PE+CRRT) for AFLP still needs evaluation. METHODS: Five AFLP patients with
      hepatic encephalopathy and renal failure were subjected to PE+CRRT in our
      department from 2007 to 2012. Their symptoms, physical signs and results were
      observed, and all relevant laboratory tests were compared before and after
      PE+CRRT. RESULTS: All the 5 patients were well tolerated to the therapy. Four of
      them responded to the treatment and showed improvement in clinical symptoms/signs
      and laboratory results, and they were cured and discharged home after the
      treatment. One patient succeeded in bridging to transplantation for slowing down
      hepatic failure and its complications process after 2 treatment sessions.
      Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days
      (range 11-42), respectively. CONCLUSION: PE+CRRT is safe and effective and should
      be used immediately at the onset of hepatic encephalopathy and/or renal failure
      in patients with AFLP.

PMID- 24686547
TI  - Pancreatic head cancer in patients with chronic pancreatitis.
AB  - BACKGROUND: Chronic pancreatitis (CP) is a risk factor of pancreatic
      adenocarcinoma (PA). The discovery of a pancreatic head lesion in CP frequently
      leads to a pancreaticoduodenectomy (PD) which preceded by a multidisciplinary
      meeting (MM). The aim of this study was to evaluate the relevance between this
      indication of PD and the definitive pathological results. METHODS: Between 2000
      and 2010, all patients with CP who underwent PD for suspicion of PA without any
      histological proof were retrospectively analyzed. The operative decision has
      always been made at an MM. The definitive pathological finding was
      retrospectively confronted with the decision made at an MM, and patients were
      classified in two groups according to this concordance (group 1) or not (group
      2). Clinical and biological parameters were analyzed, preoperative imaging were
      reread, and confronted to pathological findings in order to identify predictive
      factors of malignant degeneration. RESULTS: During the study period, five of 18
      (group 1) patients with CP had PD were histologically confirmed to have PA, and
      the other 13 (group 2) did not have PA. The median age was 52.5+/-8.2 years
      (gender ratio 3.5). The main symptoms were pain (94.4%) and weight loss (72.2%).
      There was no patient's death. Six (33.3%) patients had a major complication
      (Clavien-Dindo classification >= 3). There was no statistical difference in
      clinical and biological parameters between the two groups. The rereading of
      imaging data could not detect efficiently all patients with PA. CONCLUSIONS: Our
      results confirmed the difficulty in detecting malignant transformation in
      patients with CP before surgery and therefore an elevated rate of unnecessary PD
      was found. A uniform imaging protocol is necessary to avoid PD as a less invasive
      treatment could be proposed.

PMID- 24686546
TI  - FBW7 increases chemosensitivity in hepatocellular carcinoma cells through
      suppression of epithelial-mesenchymal transition.
AB  - BACKGROUND: FBW7 is a tumor suppressor which regulates a network of proteins with
      central roles in cell division, cell growth and differentiation. This study aimed
      to evaluate the role of FBW7 in chemosensitivity and epithelial-mesenchymal
      transition (EMT) in different hepatocellular carcinoma (HCC) cell lines and to
      investigate the relevant underlying mechanisms. METHODS: Different human HCC cell
      lines (Hep3B, Huh-7, and SNU-449) were cultured. The cell viability was evaluated
      by cell counting kit-8, and FBW7 mRNA transcription and protein expression were
      quantitated by real-time PCR and Western blotting. Expressions of vimentin
      (mesenchymal biomarker) and E-cadherin (epithelial biomarker) were evaluated by
      Western blotting and immunocytochemistry. Cell invasion was assayed by Transwell
      migration, and FBW7 plasmid or siRNA was used to evaluate the effect of FBW7
      overexpression or silencing on cell chemosensitivity. RESULTS: FBW7 expression
      affected tumor cell chemosensitivity to doxorubicin and tumor cell invasive
      capacity in different HCC cell lines. FBW7hi (high FBW7 expression) Hep3B and
      FBW7mi (median FBW7 expression) Huh-7 cells were more sensitive to doxorubicin
      and lower in invasive capacity than FBW7lo (low FBW7 expression) SNU-449 cells.
      Silencing of FBW7 in Huh-7 and Hep3B cells induced the resistance to doxorubicin
      and enhanced cell invasion, whereas overexpression of FBW7 in SNU-449 cells
      restored the sensitivity to doxorubicin and significantly reduced invasive
      capacity. Furthermore, doxorubicin induced EMT toward mesenchyme in HCC cells.
      Downregulation of FBW7 in Huh-7 and Hep3B cells or upregulation of FBW7 in SNU
      449 cells altered the direction of EMT. CONCLUSIONS: The level of FBW7 expression
      impacted the tumor resistance to doxorubicin and the invasion capability of HCC
      cells. FBW7 therefore may be a potential target for the chemotherapy of HCC
      through the regulation of EMT.

PMID- 24686548
TI  - Multi-visceral resection of locally advanced extra-pancreatic carcinoma.
AB  - BACKGROUND: Multi-visceral resection for extra-pancreatic carcinoma is an
      uncommon procedure that may offer palliation and potential cure but must be
      balanced against the risk for morbidity and mortality. METHODS: A retrospective
      analysis was made of patients who had undergone multi-visceral resection of non
      pancreatic carcinoma. Factors influencing this procedure included histology,
      pathologic confirmation of pancreaticoduodenal invasion, tumor clearance, peri
      operative morbidity and outcome. RESULTS: Sixteen patients had en bloc resection
      including a Whipple procedure (6 patients) and a distal resection (10). Primary
      pathology mostly originated from the stomach and adenocarcinoma was predominately
      histological. An R0 resection was made in 13 patients, and actual cancer invasion
      or abutment into the pancreas or duodenum was confirmed pathologically in 11
      patients. Twelve patients suffered from at least one complication. Ten patients
      required therapeutic intervention for complications. There were 2 in-hospital
      deaths. The median survival of deceased patients was 7.5 months. Six patients are
      alive at a median of 21 months, and 4 patients have no evidence of disease to the
      present. CONCLUSIONS: Multi-visceral resections for extra-pancreatic carcinoma
      are associated with substantial morbidity that requires therapeutic intervention.
      Clinical determination of pancreaticoduodenal abutment and achievement of tumor
      clearance is excellent. Survival with and without recurrent disease is often
      limited, supporting that it is necessary to cautiously perform the aggressive
      procedures in consideration of neoadjuvant therapy.

PMID- 24686549
TI  - Pancreatic fistula after central pancreatectomy: case series and review of the
      literature.
AB  - BACKGROUND: Postoperative pancreatic fistula is one of the most common
      complications after pancreatectomy. This study aimed to assess the occurrence and
      severity of pancreatic fistula after central pancreatectomy. METHODS: The medical
      records of 13 patients who had undergone central pancreatectomy were
      retrospectively studied, together with a literature review of studies including
      at least five cases of central pancreatectomy. Pancreatic fistula was defined and
      graded according to the recommendations of the International Study Group on
      Pancreatic Fistula (ISGPF). RESULTS: No death was observed in the 13 patients.
      Pancreatic fistula developed in 7 patients and was successfully treated non
      operatively. None of these patients required re-operation. A total of 40 studies
      involving 867 patients who underwent central pancreatectomy were reviewed. The
      overall pancreatic fistula rate of the patients was 33.4% (0-100%). Of 279
      patients, 250 (89.6%) had grade A or B fistulae of ISGPF and were treated non
      operatively, and the remaining 29 (10.4%) had grade C fistulae of ISGPF. In 194
      patients, 15 (7.7%) were re-operated upon. Only one patient with grade C fistula
      of ISGPF died from multiple organ failure after re-operation. CONCLUSION: Despite
      the relatively high occurrence, most pancreatic fistulae after central
      pancreatectomy are recognized a grade A or B fistula of ISGPF, which can be
      treated conservatively or by mini-invasive approaches.

PMID- 24686550
TI  - Familial chylomicronemia syndrome related chronic pancreatitis: a single-center
      study.
AB  - BACKGROUND: Hypertriglyceridemia induces acute recurrent pancreatitis, but its
      role in the etiology of chronic pancreatitis (CP) is controversial. This study
      aimed to evaluate the clinical, laboratory and radiological findings of 7
      patients with CP due to type 1 hyperlipidemia compared to CP patients with other
      or undefined etiological factors. METHODS: We retrospectively analyzed the
      clinical, laboratory and radiological findings of 7 CP patients with type 1
      hyperlipidemia compared to CP patients without hypertriglyceridemia. These 7
      patients had multiple episodes of acute pancreatitis and had features of CP on
      abdominal CT, endoscopic retrograde cholangiopancreatography and/or endoscopic
      ultrasonography. RESULTS: All CP patients were classified into two groups: a
      group with type 1 hyperlipidemia (n=7) and a group with other etiologies (n=58).
      The mean triglyceride level was 2323+/-894 mg/dL in the first group. Age at the
      diagnosis of CP in the first group was significantly younger than that in the
      second group (16.5+/-5.9 vs 48.3+/-13.5, P<0.001). The number of episodes of
      acute pancreatitis in the first group was significantly higher than that in the
      second group (15.0+/-6.8 vs 4.0+/-4.6, P=0.011). The number of splenic vein
      thrombosis in the first group was significantly higher than that in the second
      group (4/7 vs 9/58, P=0.025). Logistic regression analysis found that younger age
      was an independent predictor of CP due to hypertriglyceridemia (r=0.418,
      P=0.000). CONCLUSIONS: Type 1 hyperlipidemia appears to be an etiological factor
      even for a minority of patients with CP. It manifests at a younger age, and the
      course of the disease might be severe.

PMID- 24686551
TI  - Instrumental detection of cystic duct stones during laparoscopic cholecystectomy.
AB  - Residual cystic duct stones (CDSs) after cholecystectomy have been recognized as
      a cause of post-cholecystectomy pain. This study was undertaken to determine the
      incidence of CDSs during laparoscopic cholecystectomy (LC). A cohort of 330
      consecutive patients (80 males and 250 females) undergoing LC between November
      2006 and May 2010 was studied. Their age ranged between 16 and 88 years (median
      50, IQR: 36.62). The data were prospectively collected of preoperative liver
      function tests, imaging, the presence of intraoperative CDSs, and common bile
      duct stones at on-table cholangiogram. CDSs were detected intraoperatively in 64
      of the 330 patients (19%). Ultrasound failed to detect CDSs in any of these
      cases. Deranged liver function tests were noted in 73% of the patients with CDSs
      and in 57% without CDSs. Common bile duct stones were detected in 9% (29) of the
      330 patients. CDSs occur commonly at routine cholecystectomy, and preoperative
      investigations are not helpful in their diagnosis. As CDSs may lead to
      postoperative morbidity, they should be actively sought out during surgery if
      present. 

PMID- 24686552
TI  - Improved anterior hepatic transection for isolated hepatocellular carcinoma in
      the caudate.
AB  - BACKGROUND: One of the best treatments for isolated hepatocellular carcinoma in
      the caudate lobe is major hepatectomy with caudate lobectomy, but it is not
      suitable for patients with poor liver function reserve. Isolated caudate
      lobectomy, which is a very difficult operation, is thus an alternative option.
      METHODS: Here we report an isolated caudate lobectomy with an anterior approach
      in the treatment of a large hepatocellular carcinoma with underlying cirrhosis,
      with focus on the technical aspects. RESULTS: In the operation, both the left and
      right lobes of the liver were mobilized. Hepatotomy was done along the round
      ligament where parenchymal transection was minimal. After exposure of the left
      and middle hepatic veins and the hilar plate, the caudate lobe and the tumor were
      resected en bloc with a 5-mm margin. CONCLUSION: Isolated caudate lobectomy can
      be performed safely with this anterior approach on patients with poor liver
      function reserve.

PMID- 24686554
TI  - Preparation of segmented microtubules to study motions driven by the
      disassembling microtubule ends.
AB  - Microtubule depolymerization can provide force to transport different protein
      complexes and protein-coated beads in vitro. The underlying mechanisms are
      thought to play a vital role in the microtubule-dependent chromosome motions
      during cell division, but the relevant proteins and their exact roles are ill
      defined. Thus, there is a growing need to develop assays with which to study such
      motility in vitro using purified components and defined biochemical milieu.
      Microtubules, however, are inherently unstable polymers; their switching between
      growth and shortening is stochastic and difficult to control. The protocols we
      describe here take advantage of the segmented microtubules that are made with the
      photoablatable stabilizing caps. Depolymerization of such segmented microtubules
      can be triggered with high temporal and spatial resolution, thereby assisting
      studies of motility at the disassembling microtubule ends. This technique can be
      used to carry out a quantitative analysis of the number of molecules in the
      fluorescently-labeled protein complexes, which move processively with dynamic
      microtubule ends. To optimize a signal-to-noise ratio in this and other
      quantitative fluorescent assays, coverslips should be treated to reduce
      nonspecific absorption of soluble fluorescently-labeled proteins. Detailed
      protocols are provided to take into account the unevenness of fluorescent
      illumination, and determine the intensity of a single fluorophore using
      equidistant Gaussian fit. Finally, we describe the use of segmented microtubules
      to study microtubule-dependent motions of the protein-coated microbeads,
      providing insights into the ability of different motor and nonmotor proteins to
      couple microtubule depolymerization to processive cargo motion. 

PMID- 24686553
TI  - Gap detection in school-age children and adults: effects of inherent envelope
      modulation and the availability of cues across frequency.
AB  - PURPOSE: The present study evaluated the effects of inherent envelope modulation
      and the availability of cues across frequency on behavioral gap detection with
      noise-band stimuli in school-age children. METHOD: Listeners were 34 normal
      hearing children (ages 5.2-15.6 years) and 12 normal-hearing adults (ages 18.5
      28.8 years). Stimuli were continuous bands of noise centered on 2000 Hz, either
      1000- or 25-Hz wide. In addition to Gaussian noise at these bandwidths, there
      were conditions using 25-Hz-wide noise bands modified to either accentuate or
      minimize inherent envelope modulation (staccato and low-fluctuation noise,
      respectively). RESULTS: Within the 25-Hz-wide conditions, adults' gap detection
      thresholds were highest in the staccato, lower in the Gaussian, and lowest in the
      low-fluctuation noise. Similar trends were evident in children's thresholds,
      although inherent envelope modulation had a smaller effect on children than on
      adults. Whereas adults' thresholds were comparable for the 1000-Hz-wide Gaussian
      and 25-Hz-wide low-fluctuation stimulus, children's performance converged on
      adults' performance at a younger age for the 1000-Hz-wide Gaussian stimulus.
      CONCLUSIONS: Results are consistent with the idea that children are less
      susceptible to the disruptive effects of inherent envelope modulation than adults
      when detecting a gap in a narrow-band noise. Further, the ability to use
      spectrally distributed gap detection cues appears to mature relatively early in
      childhood.

PMID- 24686555
TI  - Assessing articulatory speed performance as a potential factor of slowed speech
      in older adults.
AB  - PURPOSE To improve our understanding about the underlying factors of aging
      related speaking rate decline, the authors sought to determine if lip and jaw
      speeds are physiologically constrained in older adults. METHOD Thirty-six females
      10 young adults (ages 22-27 years), 9 middle-aged adults (ages 45-55 years), 10
      young-old adults (65-74 years), and 7 very old adults (ages 87-95 years)
      completed metronome-paced syllable repetitions while moving the lower lip or jaw
      to a fixed target with each repetition. Metronome paces incrementally increased
      from 1.4 Hz to 6.7 Hz. Lip and jaw movements were tracked using a 3-dimensional
      motion capture system. RESULTS Older adults' maximum percent increase in lip and
      jaw peak speed was comparable to or tended to be even greater than that of middle
      aged and young adults. By contrast, lip and jaw stiffness, indexed by peak speed
      displacement ratios, tended to decrease with age during fast and very fast
      repetition rates and were associated with mildly prolonged movement durations.
      CONCLUSIONS The findings suggest that lip and jaw speeds are not constrained in
      older adults. The trend of reduced stiffness during fast rates, however, suggests
      that fine-force regulation becomes difficult for older adults. Thus, older adults
      may implement reduced habitual speaking rates as a behavioral strategy to
      compensate for diminished articulatory control. 

PMID- 24686556
TI  - Development of a self-report tool to evaluate hearing aid outcomes among Chinese
      speakers.
AB  - PURPOSE: This article reports on the development of a self-report tool-the
      Chinese Hearing Aid Outcomes Questionnaire (CHAOQ)-to evaluate hearing aid
      outcomes among Chinese speakers. METHOD: There were 4 phases to construct the
      CHAOQ and evaluate its psychometric properties. First, items were selected to
      evaluate a range of culturally relevant outcomes. These procedures provided
      evidence for face and content validity. Second, items with inappropriate
      psychometric properties were eliminated. Items related to listening performance
      were subjected to exploratory factor analysis to identify the factor structure,
      which was later confirmed via a confirmatory factor analysis in Phase III. These
      procedures also ensured content and discriminant validity. Internal consistency
      reliability was evaluated, and normative data were obtained. Finally, test-retest
      reliability was evaluated, and construct validity was established by comparing
      results with corresponding items from the International Outcome Inventory for
      Hearing Aids. RESULTS: The final 26-item CHAOQ contains (a) 3 scales evaluating
      speech understanding in situations in which communication is relatively more
      difficult or easy or includes reduced listening cues; (b) a scale evaluating
      listening comfort; (c) a scale measuring negative responses; and (d) an item
      measuring overall satisfaction. CONCLUSION: The CHAOQ possesses good reliability
      and validity.

PMID- 24686557
TI  - Seven new and two known lipopeptides as well as five known polyketides: the
      activated production of silent metabolites in a marine-derived fungus by chemical
      mutagenesis strategy using diethyl sulphate.
AB  - AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a
      marine-derived Penicillium purpurogenum G59. The G59 strain originally did not
      produce any metabolites with antitumor activities in MTT assays using K562 cells.
      Tracing newly produced metabolites under guidance of MTT assay and TLC analysis
      by direct comparison with control G59 extract, seven new (1-7) and two known (8
      9) lipopeptides were isolated together with five known polyketides 10-14 from the
      extract of mutant AD-2-1. Structures of the seven new compounds including their
      absolute configurations were determined by spectroscopic and chemical evidences
      and named as penicimutalides A-G (1-7). Seven known compounds were identified as
      fellutamide B (8), fellutamide C (9), 1'-O-methylaverantin (10), averantin (11),
      averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1-14
      inhibited several human cancer cell lines to varying extents. All the bioassays
      and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization
      (ESI)-MS analyses demonstrated that the production of 1-14 in the mutant AD-2-1
      was caused by the activated production of silent metabolites in the original G59
      fungal strain. Present results provided additional examples for effectiveness of
      the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover
      new compounds by activating silent metabolites in fungal isolates. 

PMID- 24686558
TI  - Structure activity relationship of brevenal hydrazide derivatives.
AB  - Brevenal is a ladder frame polyether produced by the dinoflagellate Karenia
      brevis. This organism is also responsible for the production of the neurotoxic
      compounds known as brevetoxins. Ingestion or inhalation of the brevetoxins leads
      to adverse effects such as gastrointestinal maladies and bronchoconstriction.
      Brevenal shows antagonistic behavior to the brevetoxins and shows beneficial
      attributes when administered alone. For example, in an asthmatic sheep model,
      brevenal has been shown to increase tracheal mucosal velocity, an attribute which
      has led to its development as a potential treatment for Cystic Fibrosis. The
      mechanism of action of brevenal is poorly understood and the exact binding site
      has not been elucidated. In an attempt to further understand the mechanism of
      action of brevenal and potentially develop a second generation drug candidate, a
      series of brevenal derivatives were prepared through modification of the aldehyde
      moiety. These derivatives include aliphatic, aromatic and heteroaromatic
      hydrazide derivatives. The brevenal derivatives were tested using in vitro
      synaptosome binding assays to determine the ability of the compounds to displace
      brevetoxin and brevenal from their native receptors. A sheep inhalation model was
      used to determine if instillation of the brevenal derivatives resulted in
      bronchoconstriction. Only small modifications were tolerated, with larger
      moieties leading to loss of affinity for the brevenal receptor and
      bronchoconstriction in the sheep model. 

PMID- 24686559
TI  - Marine natural products acting on the acetylcholine-binding protein and nicotinic
      receptors: from computer modeling to binding studies and electrophysiology.
AB  - For a small library of natural products from marine sponges and ascidians, in
      silico docking to the Lymnaea stagnalis acetylcholine-binding protein (AChBP), a
      model for the ligand-binding domains of nicotinic acetylcholine receptors
      (nAChRs), was carried out and the possibility of complex formation was revealed.
      It was further experimentally confirmed via competition with radioiodinated alpha
      bungarotoxin ([125I]-alphaBgt) for binding to AChBP of the majority of analyzed
      compounds. Alkaloids pibocin, varacin and makaluvamines S and G had relatively
      high affinities (K(i) 0.5-1.3 MUM). With the muscle-type nAChR from Torpedo
      californica ray and human neuronal alpha7 nAChR, heterologously expressed in the
      GH4C1 cell line, no competition with [125I]-alphaBgt was detected in four
      compounds, while the rest showed an inhibition. Makaluvamines (K(i) ~ 1.5 MUM)
      were the most active compounds, but only makaluvamine G and crambescidine 359
      revealed a weak selectivity towards muscle-type nAChR. Rhizochalin, aglycone of
      rhizochalin, pibocin, makaluvamine G, monanchocidin, crambescidine 359 and
      aaptamine showed inhibitory activities in electrophysiology experiments on the
      mouse muscle and human alpha7 nAChRs, expressed in Xenopus laevis oocytes. Thus,
      our results confirm the utility of the modeling studies on AChBPs in a search for
      natural compounds with cholinergic activity and demonstrate the presence of the
      latter in the analyzed marine biological sources.

PMID- 24686560
TI  - NMR-based metabolomic analysis of spatial variation in soft corals.
AB  - Soft corals are common marine organisms that inhabit tropical and subtropical
      oceans. They are shown to be rich source of secondary metabolites with biological
      activities. In this work, soft corals from two geographical locations were
      investigated using 1H-NMR spectroscopy coupled with multivariate statistical
      analysis at the metabolic level. A partial least-squares discriminant analysis
      showed clear separation among extracts of soft corals grown in Sanya Bay and
      Weizhou Island. The specific markers that contributed to discrimination between
      soft corals in two origins belonged to terpenes, sterols and N-containing
      compounds. The satisfied precision of classification obtained indicates this
      approach using combined 1H-NMR and chemometrics is effective to discriminate soft
      corals collected in different geographical locations. The results revealed that
      metabolites of soft corals evidently depended on living environmental condition,
      which would provide valuable information for further relevant coastal marine
      environment evaluation.

PMID- 24686561
TI  - Articulatory closure proficiency in patients with Parkinson's disease following
      deep brain stimulation of the subthalamic nucleus and caudal zona incerta.
AB  - PURPOSE: The present study aimed at comparing the effects of deep brain
      stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona
      incerta (cZi) on the proficiency in achieving oral closure and release during
      plosive production of people with Parkinson's disease. METHOD: Nineteen patients
      participated preoperatively and 12 months after DBS surgery. Nine patients had
      implantations in the STN, 7 bilaterally and 2 unilaterally (left). Ten had
      bilateral implantations in the cZi. Postoperative examinations were made off and
      on stimulation. All patients received simultaneous L-dopa treatment in all
      conditions. For a series of plosives extracted from a reading passage, absolute
      and relative measures of duration of frication and amplitude of plosive release
      were compared between conditions within each treatment group. RESULTS: Relative
      duration of frication increased in voiceless plosives in the on-stimulation
      condition in cZi patients. Similar trends were observed across the data set.
      Duration of prerelease frication and the release peak prominence increased in
      voiceless plosives on stimulation for both groups. CONCLUSION: The increased
      release prominence suggests that patients achieved a stronger closure gesture
      because of DBS but that the increased energy available resulted in increased
      frication.

PMID- 24686562
TI  - The use of gas chromatography to analyze compositional changes of fatty acids in
      rat liver tissue during pregnancy.
AB  - Gas chromatography (GC) is a highly sensitive method used to identify and
      quantify the fatty acid content of lipids from tissues, cells, and plasma/serum,
      yielding results with high accuracy and high reproducibility. In metabolic and
      nutrition studies GC allows assessment of changes in fatty acid concentrations
      following interventions or during changes in physiological state such as
      pregnancy. Solid phase extraction (SPE) using aminopropyl silica cartridges
      allows separation of the major lipid classes including triacylglycerols,
      different phospholipids, and cholesteryl esters (CE). GC combined with SPE was
      used to analyze the changes in fatty acid composition of the CE fraction in the
      livers of virgin and pregnant rats that had been fed various high and low fat
      diets. There are significant diet/pregnancy interaction effects upon the omega-3
      and omega-6 fatty acid content of liver CE, indicating that pregnant females have
      a different response to dietary manipulation than is seen among virgin females. 

PMID- 24686564
TI  - 'It's springtime for science': renewing China-UK scientific relations in the
      1970s.
AB  - This paper examines how links between the People's Republic of China and the UK
      were rebuilt in the 1970s. It not only fills a gap in the historiography but also
      makes three particular arguments. The first is that there were two intersecting
      institutional paths along which the rebuilding of links were followed: a foreign
      policy path, in which the most important body was the Foreign and Commonwealth
      Office, and an academy-level path in which relations between the Royal Society
      and the Chinese Academy of Sciences (also known in the early years as the
      Academia Sinica) were crucial. Especially under conditions in which access and
      travel to China were extremely restricted, the Royal Society acted as a
      'gatekeeper', rationing visits to a select few researchers. The second argument
      is that science was a strategic pathfinder or diplomatic 'avant garde'. The
      maintenance of scientific links, even during the most difficult periods of this
      history when they were all but severed, meant that a path was kept open to
      'further communication and exchange between peoples-and governments', as Kathlin
      Smith has found in the broadly similar case of relations between China and the
      USA. In particular, scientific relations formed an important bridge in the
      negotiation and eventual agreement of the first treaty signed between the UK and
      communist China in 1978. It was no coincidence that this highest-level political
      agreement was accompanied by a parallel accord between the scientific academies.
      Third, I argue that, nevertheless, even this treaty was not entirely new, and
      that the model for the China-UK treaty was existing agreements on technology
      exchanges made with Eastern European countries.

PMID- 24686563
TI  - Whisker barrel cortex delta oscillations and gamma power in the awake mouse are
      linked to respiration.
AB  - Current evidence suggests that delta oscillations (0.5-4 Hz) in the brain are
      generated by intrinsic network mechanisms involving cortical and thalamic
      circuits. Here we report that delta band oscillation in spike and local field
      potential (LFP) activity in the whisker barrel cortex of awake mice is phase
      locked to respiration. Furthermore, LFP oscillations in the gamma frequency band
      (30-80 Hz) are amplitude modulated in phase with the respiratory rhythm. Removal
      of the olfactory bulb eliminates respiration-locked delta oscillations and delta
      gamma phase-amplitude coupling. Our findings thus suggest respiration-locked
      olfactory bulb activity as a main driving force behind delta oscillations and
      gamma power modulation in the whisker barrel cortex in the awake state.

PMID- 24686565
TI  - Water-soluble pyrrolopyrrole cyanine (PPCy) NIR fluorophores.
AB  - Water-soluble derivatives of pyrrolopyrrole cyanines (PPCys) have been
      synthesized by a post-synthetic modification route. In highly polar media, these
      dyes are excellent NIR fluorophores. Labeling experiments show how these novel
      dyes are internalized into mammalian cells. 

PMID- 24686566
TI  - Isolated cognitive relapses in multiple sclerosis.
AB  - OBJECTIVE: While cognition can be affected during sensorimotor multiple sclerosis
      (MS) relapses, the relevance of isolated cognitive relapses (ICRs ie, those
      occurring in absence of new sensorimotor symptoms) remain poorly characterised.
      Here, we decided to explore the relationship between ICR, subjective evaluation
      of cognitive performance and long-term cognitive decline in a group of subjects
      with relapsing-remitting MS. METHODS: We analysed the cognitive performance of 99
      clinically stable relapsing-remitting MS for whom data from four consequent
      clinical and cognitive evaluations were available, that is, a baseline evaluation
      (t0), followed in the subsequent 6 months by a second evaluation performed not
      later than 2 weeks after a routine brain scan positive for at least one area of
      gadolinium enhancement (t1) and two gadolinium enhancement-negative follow-up
      evaluations after 6 months (t2) and 1 year (t3) from t1. Based on published
      literature, we defined as a meaningful change in cognition a transient reduction
      of Symbol Digit Modalities Test score of at least four points at t1 compared with
      t0 and t2. RESULTS: ICRs were found in 17 patients and were not associated with
      subjective cognitive deficits or depression. Subjects who presented with an ICR
      at t1 presented with a significantly reduced cognitive performance at the follow
      up evaluations compared with patients without ICR. CONCLUSIONS AND RELEVANCE: We
      showed that ICRs were not associated with changes in mood, fatigue levels or
      cognitive performance self-evaluations. Our study introduces an operational
      definition of ICRs and suggests to their role as a factor for cognitive decline
      in MS.

PMID- 24686567
TI  - Voice onset time in consonant cluster errors: can phonetic accommodation
      differentiate cognitive from motor errors?
AB  - PURPOSE: Phonetic accommodation in speech errors has traditionally been used to
      identify the processing level at which an error has occurred. Recent studies have
      challenged the view that noncanonical productions may solely be due to phonetic,
      not phonological, processing irregularities, as previously assumed. The authors
      of the present study investigated the relationship between phonological and
      phonetic planning processes on the basis of voice onset time (VOT) behavior in
      consonant cluster errors. METHOD: Acoustic data from 22 German speakers were
      recorded while eliciting errors on sibilant-stop clusters. Analyses consider VOT
      duration as well as intensity and spectral properties of the sibilant. RESULTS:
      Of all incorrect responses, 28% failed to show accommodation. Sibilant intensity
      and spectral properties differed from correct responses irrespective of whether
      VOT was accommodated. CONCLUSIONS: The data overall do not allow using (a lack
      of) accommodation as a diagnostic as to the processing level at which an error
      has occurred. The data support speech production models that allow for an
      integrated view of phonological and phonetic processing.

PMID- 24686568
TI  - Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell
      cycle progression in rice.
AB  - We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone
      and in combination with positive or neutral hormones, including salicylic acid
      (SA), on rice growth and expression of cell cycle-related genes. ABA
      significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5,
      and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6
      interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied
      with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA
      also blocked ABA inhibition of DNA replication and thymidine incorporation in the
      shoot apical meristem. These results suggest that ABA arrests cell cycle
      progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit
      the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP
      genes. 

PMID- 24686570
TI  - Contributions of children's linguistic and working memory proficiencies to their
      judgments of grammaticality.
AB  - PURPOSE: The authors explored the cognitive mechanisms involved in language
      processing by systematically examining the performance of children with deficits
      in the domains of working memory and language. METHOD: From a database of 370
      school-age children who had completed a grammaticality judgment task, groups were
      identified with a co-occurring language and working memory impairment (LI-WMI; n
      = 18) or specific language impairment (SLI) with typical working memory skills (
      n = 60) and matched control groups. Correct and incorrect use of grammatical
      markers occurred either early or late in sentence stimuli, imposing a greater
      working memory load for late-marker sentences. RESULTS: Children with SLI showed
      a lower preference for grammatical items than typically developing controls,
      regardless of error marker position. Children with LI-WMI demonstrated a
      performance pattern modulated by error marker position: Their preference for
      grammatical items was lower than typically developing controls for late but not
      early marker sentences. CONCLUSION: This pattern of results suggests that there
      are distinct and dissociable impacts of working memory and linguistic skills on
      metalinguistic functioning through a grammatical judgment task.

PMID- 24686569
TI  - Native SDS-PAGE: high resolution electrophoretic separation of proteins with
      retention of native properties including bound metal ions.
AB  - Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is commonly
      used to obtain high resolution separation of complex mixtures of proteins. The
      method initially denatures the proteins that will undergo electrophoresis.
      Although covalent structural features of resolved proteins can be determined with
      SDS-PAGE, functional properties are destroyed, including the presence of non
      covalently bound metal ions. To address this shortcoming, blue-native (BN)-PAGE
      has been introduced. This method retains functional properties but at the cost of
      protein resolving power. To address the need for a high resolution PAGE method
      that results in the separation of native proteins, experiments tested the impact
      of changing the conditions of SDS-PAGE on the quality of protein separation and
      retention of functional properties. Removal of SDS and EDTA from the sample
      buffer together with omission of a heating step had no effect on the results of
      PAGE. Reduction of SDS in the running buffer from 0.1% to 0.0375% together with
      deletion of EDTA also made little impact on the quality of the
      electrophoretograms of fractions of pig kidney (LLC-PK1) cell proteome in
      comparison with that achieved with the SDS-PAGE method. The modified conditions
      were called native (N)SDS-PAGE. Retention of Zn(2+) bound in proteomic samples
      increased from 26 to 98% upon shifting from standard to modified conditions.
      Moreover, seven of nine model enzymes, including four Zn(2+) proteins that were
      subjected to NSDS-PAGE retained activity. All nine were active in BN-PAGE,
      whereas all underwent denaturation during SDS-PAGE. Metal retention after
      electrophoresis was additionally confirmed using laser ablation-inductively
      coupled plasma-mass spectrometry and in-gel Zn-protein staining using the
      fluorophore TSQ. 

PMID- 24686571
TI  - Multiple factors are involved in the dysarthria associated with Parkinson's
      disease: a review with implications for clinical practice and research.
AB  - PURPOSE: Motor speech abnormalities are highly common and debilitating in
      individuals with idiopathic Parkinson's disease (IPD). These abnormalities,
      collectively termed hypokinetic dysarthria (HKD), have been traditionally
      attributed to hypokinesia and bradykinesia secondary to muscle rigidity and
      dopamine deficits. However, the role of rigidity and dopamine in the development
      of HKD is far from clear. The purpose of the present study was to offer an
      alternative view of the factors underlying HKD. METHOD: The authors conducted an
      extensive, but not exhaustive, review of the literature to examine the evidence
      for the traditional view versus the alternative view. RESULTS: The review
      suggests that HKD is a highly complex and variable phenomenon including multiple
      factors, such as scaling and maintaining movement amplitude and effort;
      preplanning and initiation of movements; internal cueing; sensory and temporal
      processing; automaticity; emotive vocalization; and attention to action (vocal
      vigilance). Although not part of the dysarthria, nonmotor factors, such as
      depression, aging, and cognitive-linguistic abnormalities, are likely to
      contribute to the overall speech symptomatology associated with IPD. CONCLUSION:
      These findings have important implications for clinical practice and research.

PMID- 24686573
TI  - Reduced itraconazole concentration and durations are successful in treating
      Batrachochytrium dendrobatidis infection in amphibians.
AB  - Amphibians are experiencing the greatest decline of any vertebrate class and a
      leading cause of these declines is a fungal pathogen, Batrachochytrium
      dendrobatidis (Bd), which causes the disease chytridiomycosis. Captive assurance
      colonies are important worldwide for threatened amphibian species and may be the
      only lifeline for those in critical threat of extinction. Maintaining disease
      free colonies is a priority of captive managers, yet safe and effective
      treatments for all species and across life stages have not been identified. The
      most widely used chemotherapeutic treatment is itraconazole, although the dosage
      commonly used can be harmful to some individuals and species. We performed a
      clinical treatment trial to assess whether a lower and safer but effective dose
      of itraconazole could be found to cure Bd infections. We found that by reducing
      the treatment concentration from 0.01-0.0025% and reducing the treatment duration
      from 11-6 days of 5 min baths, frogs could be cured of Bd infection with fewer
      side effects and less treatment-associated mortality. 

PMID- 24686574
TI  - Prevalence of mental illnesses in US State prisons: a systematic review.
AB  - Two federal reports dating from 1999 and 2006 are by far the most widely cited
      sources for the prevalence of mental illness among persons in U.S. jails and
      prisons. To provide a broader picture of the issue, the author undertook a
      systematic review of 28 articles published between 1989 and 2013. Not only did
      the review confirm the high prevalence of mental illnesses among prisoners, it
      identified a litany of health problems associated with the incarceration of
      persons with mental illness and profound difficulties in finding housing and
      employment after release. 

PMID- 24686575
TI  - N-substituted 2-isonicotinoylhydrazinecarboxamides--new antimycobacterial active
      molecules.
AB  - This report presents a new modification of the isoniazid (INH) structure linked
      with different anilines via a carbonyl group obtained by two synthetic procedures
      and with N-substituted 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-amines prepared by
      their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS
      and elemental analyses and were evaluated in vitro for their antimycobacterial
      activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium 330/88,
      Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii
      6509/96. 2-Isonicotinoyl-N-(4-octylphenyl)hydrazinecarboxamide displayed an in
      vitro efficacy comparable to that of INH for M. tuberculosis with minimum
      inhibitory concentrations (MICs) of 1-2 MUM. Among the halogenated derivatives,
      the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6
      trichlorophenyl)hydrazinecarboxamide (MIC=4 MUM). In silico modelling on the
      enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl
      substituents are advantageous for the interactions and affinity to InhA. Most of
      the hydrazinecarboxamides, especially those derived from 4-alkylanilines,
      exhibited significant activity against INH-resistant nontuberculous mycobacteria.

PMID- 24686576
TI  - Interaction between different extracts of Hypericum perforatum L. from Serbia and
      pentobarbital, diazepam and paracetamol.
AB  - Herb-drug interactions are an important safety concern and this study was
      conducted regarding the interaction between the natural top-selling
      antidepressant remedy Hypericum perforatum (Hypericaceae) and conventional drugs.
      This study examined the influence of acute pretreatment with different extracts
      of Hypericum perforatum from Serbia on pentobarbital-induced sleeping time,
      impairment of motor coordination caused by diazepam and paracetamol
      pharmacokinetics in mice. Ethanolic extract, aqueous extract, infusion, tablet
      and capsule of Hypericum perforatum were used in this experiment. The profile of
      Hypericum perforatum extracts as well as paracetamol plasma concentration was
      determined using RP-HPLC analysis. By quantitative HPLC analysis of active
      principles, it has been proven that Hypericum perforatum ethanolic extract has
      the largest content of naphtodianthrones: hypericin (57.77 ug/mL) and
      pseudohypericin (155.38 ug/mL). Pretreatment with ethanolic extract of Hypericum
      perforatum potentiated the hypnotic effect of pentobarbital and impairment of
      motor coordination caused by diazepam to the greatest extent and also increased
      paracetamol plasma concentration in comparison to the control group. These
      results were in correlation with naphtodianthrone concentrations. The obtained
      results have shown a considerable influence of Hypericum perforatum on
      pentobarbital and diazepam pharmacodynamics and paracetamol pharmacokinetics. 

PMID- 24686577
TI  - Structures of two new flavonoids and effects of licorice phenolics on vancomycin
      resistant Enterococcus species.
AB  - Since our previous study revealed that several licorice phenolics have
      antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA), and
      suppressive effects on the oxacillin resistance of MRSA, we further investigated
      effectiveness of licorice constituents on vancomycin-resistant Enterococcus (VRE)
      bacteria, and purified 32 phenolic compounds. Two flavonoids among them were
      characterized structurally, and identified their structures as demethylglycyrol
      (31) and 5,7-di-O-methylluteone (32), respectively. Examination of antibacterial
      effects of licorice phenolics showed that 3-arylcoumarins such as
      licoarylcoumarin (9) and glycycoumarin (26), and 2-arylcoumarones such as
      gancaonin I (17), have moderate to potent antibacterial effects on the VRE
      strains used in this study. 

PMID- 24686578
TI  - Further mulinane and azorellane diterpenoids isolated from Mulinum crassifolium
      and Azorella compacta.
AB  - The new mulinane diterpenoids 1 and 2 were isolated from the EtOAc extract of
      Mulinum crassifolium, while the rearranged mulinane 5, which was isolated for the
      first time from a natural source, was isolated from Azorella compacta. Compounds
      1-2 were prepared by semi-synthesis thorough acetylation of the diterpene 17
      acetoxymulinic acid (3). A mechanism of reaction was proposed, while the
      structures of the new compounds were elucidated on the basis of comprehensive
      spectroscopic analysis and computational methods. 

PMID- 24686580
TI  - Propionic acid and its esterified derivative suppress the growth of methicillin
      resistant Staphylococcus aureus USA300.
AB  - Previously, we demonstrated that Propionibacterium acnes, a human skin commensal
      bacterium, ferments glycerol into short-chain fatty acids, including propionic
      acid. Propionic acid suppressed the growth of Staphylococcus aureus USA300, a
      community-acquired methicillin-resistant bacterium, in vitro and in vivo. In this
      study, it is demonstrated that the anti-USA300 activity of propionic acid
      persisted after buffering the acid with 4-(2-hydroxyethyl)-1-
      piperazineethanesulfonic acid. This suggests that the growth suppression of
      USA300 mainly resulted from the antimicrobial activity of propionic acid per se
      and not from the acidity of the medium. In addition, proprionic acid
      significantly reduced the intracellular pH of USA300 and exhibited broad-spectrum
      antimicrobial activity against Escherichia coli and Candida albicans. P. acnes
      showed a higher tolerance to propionic acid. Next, an esterified derivative of
      propionic acid was synthesised. Propionic acid and the esterified derivative were
      equivalent in their efficacy to suppress the growth of USA300 in vitro. The
      esterified derivative thus provides an alternative to propionic acid as an
      antimicrobial agent against S. aureus. 

PMID- 24686581
TI  - Evading the strength-ductility trade-off dilemma in steel through gradient
      hierarchical nanotwins.
AB  - The strength-ductility trade-off has been a long-standing dilemma in materials
      science. This has limited the potential of many structural materials, steels in
      particular. Here we report a way of enhancing the strength of twinning-induced
      plasticity steel at no ductility trade-off. After applying torsion to cylindrical
      twinning-induced plasticity steel samples to generate a gradient nanotwinned
      structure along the radial direction, we find that the yielding strength of the
      material can be doubled at no reduction in ductility. It is shown that this
      evasion of strength-ductility trade-off is due to the formation of a gradient
      hierarchical nanotwinned structure during pre-torsion and subsequent tensile
      deformation. A series of finite element simulations based on crystal plasticity
      are performed to understand why the gradient twin structure can cause
      strengthening and ductility retention, and how sequential torsion and tension
      lead to the observed hierarchical nanotwinned structure through activation of
      different twinning systems. 

PMID- 24686583
TI  - Quantifying the effort individuals with aphasia invest in working memory tasks
      through heart rate variability.
AB  - PURPOSE: The objective of this study was to quantify cognitive effort that
      individuals with aphasia and neurologically intact participants dedicate to
      verbal compared with spatial working memory tasks by using a physiological
      measure of effort: heart rate variability (HRV). METHOD: Participants included 8
      individuals with aphasia and 19 neurologically intact adults. Participants
      completed 3 verbal and 3 spatial working memory tasks that varied in difficulty.
      Performance accuracy and effort allocated to tasks was recorded. Effort was
      quantified as the change in the 0.07-0.14 Hz band of HRV from baseline to task
      conditions. RESULTS: Results indicated that individuals with aphasia and control
      participants allocated effort to verbal and spatial working memory tasks. Unlike
      the control participants, participants with aphasia did not differentially invest
      effort based on task difficulty. Neither group allocated effort differentially
      based on task type. CONCLUSIONS: Results of the physiological data provide
      preliminary support for accounts indicating that individuals with aphasia do not
      properly allocate effort to cognitive-linguistic tasks. Analysis of the Group *
      Difficulty interaction indicated that the aphasia group did not allocate extra
      effort when it was required. The lack of a difference in HRV for spatial and
      verbal tasks suggests that this difference is not specific to verbal stimuli.

PMID- 24686582
TI  - Assessing plural morphology in children acquiring /s/-leniting dialects of
      Spanish.
AB  - PURPOSE: To examine the production of plural morphology in children acquiring a
      dialect of Spanish with syllable-final /s/ lenition with the goal of comparing
      how plural marker omissions in the speech of these children compare with plural
      marker omissions in children with language impairment acquiring other varieties
      of Spanish. METHOD: Three production tasks were administered to children. A
      repetition task was used to examine children's production of the plural marker in
      plural noun phrases, and 2 Berko-style tasks evaluated children's production of
      the plural marker in bare nouns. Behavior on these tasks was compared with plural
      marker comprehension for each individual child. RESULTS: There was a correlation
      between children's comprehension of the plural marker and their production of the
      plural marker on plural noun phrases in the repetition task but not between
      comprehension and production of the plural marker on bare nouns in the Berko
      style tasks. CONCLUSIONS: Assessments of plural morphology as a clinical marker
      of language impairment in Spanish-speaking children may be problematic,
      especially in children acquiring dialects of Spanish with /s/ lenition, such as
      those originating in Chile, the Dominican Republic, Cuba, Puerto Rico, and
      Central America. Instead, for children acquiring /s/-leniting dialects of
      Spanish, assessments of the plural marker in noun phrases produced within a
      sentence frame may be a better indicator of acquisition than traditional Berko
      style tasks that elicit bare nouns.

PMID- 24686584
TI  - Electrical innovations, authority and consulting expertise in late Victorian
      Britain.
AB  - In this article I examine the practices of electrical engineering experts, with
      special reference to their role in the implementation of innovations in late
      Victorian electrical networks. I focus on the consulting work of two leading
      figures in the scientific and engineering world of the period, Alexander Kennedy
      and William Preece. Both were Fellows of the Royal Society and both developed
      large-scale consulting activities in the emerging electrical industry of light
      and power. At the core of the study I place the issues of trust and authority,
      and the bearing of these on the engineering expertise of consultants in late
      Victorian Britain. I argue that the ascription of expertise to these engineers
      and the trust placed in their advice were products of power relations on the
      local scale. The study seeks to unravel both the technical and the social reasons
      for authoritative patterns of consulting expertise.

PMID- 24686585
TI  - Terahertz dual-resonance bandpass filter using bilayer reformative complementary
      metamaterial structures.
AB  - A dual-resonance frequency selective surface filter in the THz range that uses
      bilayer modified complementary metamaterial structures is proposed in this
      Letter. The bandpass filter, with dual bands centered at 0.315 and 0.48 THz, uses
      a single crystal quartz substrate and is simulated, fabricated, and measured. To
      minimize the manufacturing risks of working with fragile and thin quartz
      substrates, efforts have been made to improve the transmission frequency response
      features at realizable substrate thicknesses. Experimental results from 0.1 to
      0.6 THz measured by THz time-domain spectroscopy show excellent agreement with
      the simulation results. 

PMID- 24686586
TI  - Difference of cross-spectral densities.
AB  - Generally speaking, the difference between two cross-spectral densities (CSDs)
      does not represent a correlation function. We will furnish a sufficient condition
      so that such difference be a valid CSD. Using such a condition, we will show
      through some examples how new classes of CSDs can be generated. 

PMID- 24686587
TI  - Probing ultrafast temperature changes of aqueous solutions with coherent
      terahertz pulses.
AB  - We introduce an infrared pump-terahertz probe technique to measure the
      thermalization dynamics of aqueous solutions with a time resolution <200  fs.
      This technique makes use of the sensitivity of the terahertz absorption to the
      temperature of the hydrogen bond network. The thermalization dynamics of
      different aqueous solutions are measured and compared to the dynamics inferred
      from ultrafast infrared pump-infrared probe measurements on the intramolecular
      stretch vibration of water. This technique can shed new light on important
      aspects of energy transfer and heat dynamics and is applicable to a wide range of
      systems.

PMID- 24686588
TI  - Two-way lightwave subcarrier transmission system.
AB  - This Letter proposes and demonstrates a two-way lightwave subcarrier transmission
      system employing interleavers to deliver intensity-modulated CATV/phase-modulated
      RoF/intensity-remodulated 16-QAM-OFDM signals over two 20 km SMF links. To the
      best of our knowledge, it is the first time that interleavers have been employed
      in two-way lightwave subcarrier transmission systems. The downstream light is
      successfully intensity-remodulated with a 16-QAM-OFDM signal for uplink
      transmission. We obtained excellent performance from the CNR/CSO/CTB/BER for
      CATV/RoF/16-QAM-OFDM signal transmissions. The proposed systems offer impressive
      performance features to deliver hybrid CATV/RoF/16-QAM-OFDM signals. 

PMID- 24686589
TI  - Lasing of ambient air with microjoule pulse energy pumped by a multi-terawatt
      infrared femtosecond laser.
AB  - We report on the lasing action of atmospheric air pumped by an 800 nm femtosecond
      laser pulse with peak power up to 4 TW. Lasing emission at 428 nm increases
      rapidly over a small range of pump laser power, followed by saturation above ~1.5
      TW. The maximum lasing pulse energy is measured at 2.6 MUJ corresponding to an
      emission power in the MW range, while a maximum conversion efficiency of 3.5*10(
      5) is measured at moderate pump pulse energy. The optical gain inside the
      filament plasma is estimated to be in excess of 0.7/cm. Lasing emission shows a
      doughnut profile, reflecting the spatial distribution of the pump-generated white
      light continuum that acts as a seed for the lasing. We attribute the pronounced
      saturation to the defocusing of the seed in the plasma amplifying region and to
      the saturation of the seed intensity.

PMID- 24686590
TI  - Negative-index materials: a key to "white" multilayer Fabry-Perot.
AB  - The use of negative-index materials is highly efficient for tailoring the
      spectral dispersion properties of a quarter-wavelength Bragg mirror and for
      obtaining resonant behavior of a multilayer Fabry-Perot cavity over a very large
      spectral range. An optimization method is proposed and validated on some first
      promising devices. 

PMID- 24686591
TI  - Generation of a flexible optical comb in a periodically poled lithium niobate
      waveguide.
AB  - We propose and demonstrate a technique for the generation of an optical comb with
      tunable line spacing in a periodically poled lithium niobate (PPLN) waveguide.
      The technique is implemented with four input continuous waves (CWs), which
      generate a 19-line comb tuned to the spacing of 25 and 20 GHz. We show that each
      additional CW switched on out of the quasi phase-matching band at the PPLN
      waveguide input generates the growth of six new lines. The performance of the
      comb is tested modulating the lines with a 40 Gb/s differential quadrature phase
      shift keying data, demonstrating error-free operation. Nonuniform spacing of the
      input seed CWs improves the efficiency of the line generation process.

PMID- 24686592
TI  - Generation of 103 fs mode-locked pulses by a gain linewidth-variable Nd,Y:CaF2
      disordered crystal.
AB  - We have demonstrated a diode-pumped passively mode-locked femtosecond Nd,Y:CaF2
      disordered crystal laser for the first time to our knowledge. By choosing
      appropriate Y-doping concentration, a broad fluorescence linewidth of 31 nm has
      been obtained from the gain linewidth-variable Nd,Y:CaF2 crystal. With the
      Nd,Y:CaF2 disordered crystal as gain medium, the mode-locked laser generated
      pulses with pulse duration as short as 103 fs, average output power of 89 mW, and
      repetition rate of 100 MHz. To our best knowledge, this is the shortest pulse
      generated from Nd-doped crystal lasers so far. The research results show that the
      Nd,Y:CaF2 disordered crystal will be a potential alternative as gain medium of
      repetitive chirped pulse amplification for high-peak-power lasers.

PMID- 24686593
TI  - Encoding complex fields by using a phase-only optical element.
AB  - We show that the amplitude and phase information from a two-dimensional complex
      field can be synthesized from a phase-only optical element with micrometric
      resolution. The principle of the method is based on the combination of two
      spatially sampled phase elements by using a low-pass filter at the Fourier plane
      of a 4-f optical system. The proposed encoding technique was theoretically
      demonstrated, as well as experimentally validated with the help of a phase-only
      spatial light modulator for phase encoding, a conventional CMOS camera to measure
      the amplitude of the complex field, and a Shack-Hartmann wavefront sensor to
      determine its phase. 

PMID- 24686594
TI  - Liquid crystal hyperbolic metamaterial for wide-angle negative-positive
      refraction and reflection.
AB  - We show that nanosphere dispersed liquid crystal (NDLC) metamaterial can be
      characterized in near IR spectral region as an indefinite medium whose real parts
      of effective ordinary and extraordinary permittivities are opposite in signs.
      Based on this fact we designed an electro-optic effect: an external electric
      field-driven switch between normal refraction, negative refraction, and
      reflection of TM incident electromagnetic wave from the boundary vacuum/NDLC. A
      detailed analysis of its functionality is given based on effective medium theory
      combined with a study of negative refraction in anisotropic metamaterials and
      finite elements simulations. 

PMID- 24686595
TI  - Q-factor measurements through injection locking of a semiconductor-glass hybrid
      laser with unknown intracavity losses.
AB  - The injection locking properties of a newly developed waveguide-based external
      cavity semiconductor laser have been investigated. Using the injection locking
      properties to measure the Q-factor of complex optical cavities with unknown
      internal losses, has been demonstrated for the first time. 

PMID- 24686596
TI  - Digitally enhanced optical fiber frequency reference.
AB  - We use digitally enhanced heterodyne interferometry to measure the stability of
      optical fiber laser frequency references. Suppression of laser frequency noise by
      over four orders of magnitude is achieved using post processing time delay
      interferometry, allowing us to measure the mechanical stability for frequencies
      as low as 100 MUHz. The performance of the digitally enhanced heterodyne
      interferometer platform used here is not practically limited by the dynamic range
      or bandwidth issues that can occur in feedback stabilization systems. This allows
      longer measurement times, better frequency discrimination, a reduction in
      spatially uncorrelated noise sources and an increase in interferometer
      sensitivity. An optical fiber frequency reference with the stability reported
      here, over a signal band of 20 mHz-1 Hz, has potential for use in demanding
      environments, such as space-based interferometry missions and optical flywheel
      applications.

PMID- 24686597
TI  - High gain, wide field of view concentrator for optical communications.
AB  - The field of view and gain of optical concentrators used within free space
      optical communications systems are constrained by conservation of etendue. In
      this Letter, consideration of the processes in a fluorescent concentrator leads
      to a simple design strategy for these concentrators for this application.
      Significantly, because fluorescent concentrators do not conserve etendue, this
      can lead to concentrators with wider fields of view and higher gains. A model of
      a fluorescent concentrator containing a quantum dot material suggests that it
      could have a gain 50 times higher than an etendue conserving concentrator with
      the same field of view. 

PMID- 24686598
TI  - Hotspots from nonreciprocal surface waves.
AB  - We present theoretical and numerical results for a new method of obtaining
      hotspots that relies on nonreciprocal "one-way" propagation as opposed to the
      well-known case of resonance-based hotspots. The nonreciprocal propagation is
      achieved by the breaking of time-reversal symmetry through the use of
      magnetically biased medium. The location and existence of the hotspots depends on
      the magnetic bias that results in the breaking of the time-reversal symmetry.
      This results in the intriguing possibility of switching and spatial control of
      the hotspots through the magnetic bias. 

PMID- 24686599
TI  - Interactions of nonlocal dark solitons under competing cubic-quintic
      nonlinearities.
AB  - We investigate analytically and numerically the interactions of dark solitons
      under competing nonlocal cubic and local quintic nonlinearities. It is shown that
      the self-defocusing quintic nonlinearity will strengthen the attractive
      interaction and decrease the relative distance between solitons, whereas the self
      focusing quintic nonlinearity will enhance the repulsive interaction and increase
      soliton separation. We demonstrate these results by approximate variational
      approach and direct numerical simulation. 

PMID- 24686600
TI  - Second-harmonic generation in a silicon-carbide-based photonic crystal
      nanocavity.
AB  - We demonstrate second-harmonic generation (SHG) in a silicon-carbide (SiC)-based
      heterostructure photonic crystal nanocavity by using a pulsed laser. We observe
      SHG light radiated from the SiC nanocavity and estimate the conversion efficiency
      in the cavity to be 2.59*10(-5) (=0.15  W(-1)) at an average input power of 0.17
      mW. The near-field patterns and polarization characteristics of the SHG light are
      investigated experimentally and theoretically, and the results are in
      qualitatively good agreement.

PMID- 24686601
TI  - Compositional dependence of room-temperature Stark splitting of Yb3+ in several
      popular glass systems.
AB  - The room-temperature Stark splitting properties of Yb3+ are practical and
      valuable for lasers because the working temperature of the gain media intensively
      increases with the laser output. In this Letter, the room-temperature Stark
      splitting properties of Yb3+ in several popular laser glasses are contrastively
      studied. Yb3+-doped germanate (Ge), borate (B), silicate (Si), bismuthate (Bi),
      tellurite (Te), and fluorophosphate (FP) glasses exhibit large Stark splitting
      and tend to operate close to the quasi-four-level scheme, whereas phosphate (P)
      glass shows the weakest Stark splitting and tends to operate close to the quasi
      three-level one. Due to the low thermal conductivity of the glass matrix, Yb3+
      doped P glass suffers from serious thermal problems and is difficult to achieve
      high laser output. The Stark splitting is also used to estimate the crystal-field
      strength of glass hosts and local Yb3+ ligand asymmetry degree. The results show
      that P glass shows weaker crystal-field effect and lower Yb3+ ligand asymmetry
      than Ge, Si, and B glasses.

PMID- 24686602
TI  - All-optical demultiplexing of 16-QAM signals into QPSK tributaries using four
      level optical phase quantizers.
AB  - The potential of four-level optical phase quantizers toward coherent processing
      of advanced modulation formats, such as 16-QAM, is proposed and numerically
      demonstrated. The work shows that phase quantization achieved in fiber-based
      phase-sensitive amplifiers can demultiplex 16-QAM into two quadrature phase shift
      keying (QPSK) signals, enabling subchannel switching. The numerical study
      highlights the impact of the quantizer transfer function on the performance of
      the demultiplexing process and numerically calculates the bit error rate for each
      QPSK tributary after the demultiplexing procedure. 

PMID- 24686603
TI  - Practical decomposition for physically admissible differential Mueller matrices.
AB  - The differential Mueller matrix expresses the local action of an optical medium
      on the evolution of a propagating electromagnetic field, including partially
      coherent and partially polarized waves. Here, we present a derivation of the
      differential Mueller matrix from the canonical form of Type I Mueller matrices
      without making use of the exponential generators of uniform media. We demonstrate
      how to practically obtain this parameterization numerically using an eigenvalue
      decomposition and find validity criteria to ensure that the matrix satisfies the
      constraints of a physical system. This provides a convenient tool-set to
      investigate depolarization effects and extends previous treatments of the
      differential Mueller matrix formalism. 

PMID- 24686604
TI  - Dual modulation Faraday rotation spectroscopy of HO2 in a flow reactor.
AB  - The technique of dual modulation Faraday rotation spectroscopy (DM-FRS) has been
      applied to achieve technical-noise-limited detection of HO2 at the exit of an
      atmospheric pressure flow reactor. This was implemented by combining direct
      current modulation at 51 kHz of an external cavity quantum cascade laser system
      with 610 Hz modulation of the magnetic field generated by a Helmholtz coil. The
      DM-FRS measurement had a 1.5 times better signal-to-noise ratio than a
      conventional FRS measurement acquired under identical flow reactor conditions.
      High harmonic detection of the FRS signal also eliminated the substantial offset
      associated with electromagnetic interference pickup from the Helmholtz coils that
      is observed in the conventional FRS spectrum. A noise equivalent angle of 8.9*10(
      9)  rad Hz(-1/2) was measured for the DM-FRS measurement, corresponding to a
      3sigma detection limit for HO2 of 0.35  ppmv Hz(-1/2).

PMID- 24686605
TI  - All-optical diode based on dipole modes of Kerr microcavity in asymmetric L
      shaped photonic crystal waveguide.
AB  - A design of all-optical diode in L-shaped photonic crystal waveguide is proposed
      that uses the multistability of single nonlinear Kerr microcavity with two dipole
      modes. Asymmetry of the waveguide is achieved through different couplings of the
      dipole modes with the left and right legs of the waveguide. Using coupled mode
      theory we demonstrate an extremely high transmission contrast. The direction of
      optical diode transmission can be controlled by power or frequency of injected
      light. The theory agrees with the numerical solution of the Maxwell equations. 

PMID- 24686606
TI  - Photon correlations for colloidal nanocrystals and their clusters.
AB  - Images of semiconductor "dot-in-rods" and their small clusters are studied by
      measuring the second-order correlation function with a spatially resolving
      intensified CCD camera. This measurement allows one to distinguish between a
      single dot and a cluster and, to a certain extent, to estimate the number of dots
      in a cluster. A more advanced measurement is proposed, based on higher-order
      correlations, enabling more accurate determination of the number of dots in a
      small cluster. Nonclassical features of the light emitted by such a cluster are
      analyzed. 

PMID- 24686607
TI  - Very high finesse optical-feedback cavity-enhanced absorption spectrometer for
      low concentration water vapor isotope analyses.
AB  - So far, cavity-enhanced absorption spectroscopy (CEAS) has been based on optical
      cavities with a high finesse F that, however, has been limited by mirror
      reflectivity and by cavity transmission considerations to a few times 10,000.
      Here, we demonstrate a compact near-infrared optical-feedback CEAS instrument for
      water vapor isotope ratio measurements, with F>140,000. We show that this very
      high finesse can be effectively exploited to improve the detection sensitivity to
      the full extent predicted by the increased effective path length to reach a noise
      equivalent absorption sensitivity of 5.7*10(-11)  cm(-1) Hz(-1/2) for a full
      spectrum registration (including possible effects of interference fringes and fit
      model inadequacies).

PMID- 24686608
TI  - High RF carrier frequency modulation in silicon resonators by coupling adjacent
      free-spectral-range modes.
AB  - We demonstrate the modulation of silicon ring resonators at RF carrier
      frequencies higher than the resonance linewidth by coupling adjacent free
      spectral-range (FSR) resonance modes. In this modulator scheme, the modulation
      frequency is matched to the FSR frequency. As an example, we demonstrate a 20 GHz
      modulation in a silicon ring with a resonance linewidth of only 11.7 GHz. We show
      theoretically that this modulator scheme has lower power consumption compared to
      a standard silicon ring modulator at high carrier frequencies. These results
      could enable future on-chip high-frequency analog communication and photonic
      signal processing on a silicon photonics platform.

PMID- 24686609
TI  - Switching from normal to anomalous dispersion in photonic crystal with Raman gain
      defect.
AB  - Propagation of a light through a one-dimensional photonic crystal containing a
      defect layer doped with a Raman gain medium is discussed. We demonstrate all
      optically controlled switching from normal to anomalous dispersion in such a
      structure. A group delay for the transmitted probe (Raman) pulse is investigated.
      We show that the group velocity of a Raman pulse can be tuned from subluminal to
      superluminal by varying the intensity of the pump field. 

PMID- 24686610
TI  - Optically induced mode coupling and interference in a terahertz parallel plate
      waveguide.
AB  - We demonstrate all-optical control of terahertz (THz) wavemode coupling in a
      silicon-filled parallel plate waveguide. Using an asymmetric photoexcitation of
      charge carriers on the surface of the silicon slab within the waveguide, the
      symmetry is broken, and THz light is partially coupled from TEM to higher-order
      TM modes. The resulting interference between these modes and the residual TEM
      mode leads to a strong frequency-dependent transmission modulation. This
      frequency-selective modulation is widely tunable by adjusting the relative modal
      phases by translating the excitation along the propagation direction. The
      experimental observations are well described by a numerical and analytic model of
      modal interference. 

PMID- 24686611
TI  - Improved microgrid arrangement for integrated imaging polarimeters.
AB  - For almost 20 years, microgrid polarimetric imaging systems have been built using
      a 2*2 repeating pattern of polarization analyzers. In this Letter, we show that
      superior spatial resolution is achieved over this 2*2 case when the analyzers are
      arranged in a 2*4 repeating pattern. This unconventional result, in which a more
      distributed sampling pattern results in finer spatial resolution, is also
      achieved without affecting the conditioning of the polarimetric data-reduction
      matrix. Proof is provided theoretically and through Stokes image reconstruction
      of synthesized data. 

PMID- 24686612
TI  - Dispersion-supported direct-detection mode group division multiplexing using
      commercial multimode fiber couplers.
AB  - In this Letter, an intensity-modulation direct-detection mode group multiplexing
      system is investigated. The system does not use highly modally selective optics:
      multiplexing and demultiplexing is done in commercial multimode couplers and
      modal diversity is enhanced by modulation rates far beyond the length-bandwidth
      product of the fiber. Experimental and theoretical results shown for OM1 and OM2
      fibers fully confirm this theory. 

PMID- 24686613
TI  - Hybrid multiphoton and optoacoustic microscope.
AB  - We present a hybrid microscope combining multiphoton microscopy incorporating
      second-harmonic generation contrast and optical-resolution optoacoustic
      (photoacoustic) microscopy. We study the relative performance of the two systems
      and investigate the complementarity of contrast by demonstrating the label-free
      imaging capabilities of the hybrid microscope on zebrafish larvae ex vivo,
      concurrently visualizing the fish musculature and melanocytes. This
      implementation can prove useful in multiparametric microscopy studies, enabling
      broader information to be collected from biological specimens. 

PMID- 24686614
TI  - Gigabit polarization division multiplexing in visible light communication.
AB  - In this Letter, polarization division multiplexing is proposed and experimentally
      demonstrated for the first time that we know of, in visible light communication
      systems based on incoherent light emitting diodes and two orthogonal groups of
      linear polarizers. Spectrally efficient 16-ary quadrature amplitude modulation
      Nyquist single carrier frequency domain equalization is employed to obtain a
      maximum spectral efficiency. We achieve an aggregate data rate of 1  Gb/s, with
      bit error rate results for two polarization directions both below the 7% pre
      forward-error-correction threshold of 3.8*10(-3) after 80 cm free-space
      transmission. Moreover, the cross talk between x and y polarization is also
      discussed and analyzed.

PMID- 24686615
TI  - Zero-fringe demodulation method based on location-dependent birefringence
      dispersion in polarized low-coherence interferometry.
AB  - We present a high precision and fast speed demodulation method for a polarized
      low-coherence interferometer with location-dependent birefringence dispersion.
      Based on the characteristics of location-dependent birefringence dispersion and
      five-step phase-shifting technology, the method accurately retrieves the peak
      position of zero-fringe at the central wavelength, which avoids the fringe order
      ambiguity. The method processes data only in the spatial domain and reduces the
      computational load greatly. We successfully demonstrated the effectiveness of the
      proposed method in an optical fiber Fabry-Perot barometric pressure sensing
      experiment system. Measurement precision of 0.091 kPa was realized in the
      pressure range of 160 kPa, and computation time was improved by 10 times compared
      to the traditional phase-based method that requires Fourier transform operation.

PMID- 24686616
TI  - Femtosecond amplifier similariton Yb:fiber laser at a 616 MHz repetition rate.
AB  - We report a compact Yb:fiber ring laser operated at 616 MHz. The average output
      power is 450 mW at a pump power of 900 mW. The dechirped pulse width is 98 fs.

PMID- 24686617
TI  - Birefringence compensated silicon nanowire arrayed waveguide grating for CWDM
      optical interconnects.
AB  - We demonstrate an arrayed waveguide grating based on silicon nanowires with
      birefringence compensation for optical interconnects using coarse wavelength
      division multiplexing (CWDM). Angled star couplers are employed in combination
      with different diffraction orders for TM and TE polarizations. This device has a
      compact footprint of 0.36  mm*0.17  mm. Theoretical and experimental results show
      that the polarization-dependent wavelength shifts (PDlambda) can be reduced from
      380-420 to 0.5-3.5 nm, below 25% of the 3 dB bandwidth of channel response. The
      measured cross talk for TM polarization is better than -18  dB, and that for TE
      is better than -14  dB.

PMID- 24686618
TI  - Propagation of rotational field correlation through atmospheric turbulence.
AB  - A general formulation is presented that describes the propagation of the
      rotational field correlation of an optical beam through atmospheric turbulence.
      The associated influence on the orbital angular momentum (OAM) of a single photon
      is described analytically. The analysis predicts the probability of change in the
      OAM state due to the process of propagating through turbulence. The probability
      of a change in an OAM state depends on the Fresnel number and on the ratio of the
      beam diameter to the Fried parameter. 

PMID- 24686619
TI  - Inverted-wedge silica resonators for controlled and stable coupling.
AB  - Silica microresonators with an inverted-wedge shape were fabricated using
      conventional semiconductor fabrication methods. The measured quality factors of
      the resonators were greater than 10(6) in 1550 nm band. Controllable coupling
      from undercoupling to the overcoupling regime through the critical coupling point
      was demonstrated by horizontally moving a fiber taper while in touch with the top
      surface of the resonator. The thin outer ring of the resonator provided a support
      for the fiber taper leading to robust stable coupling.

PMID- 24686620
TI  - Superficial radially resolved fluorescence and 3D photochemical time-dependent
      model for photodynamic therapy.
AB  - Photodynamic therapy (PDT) dosimetric tools are crucial for treatment planning
      and noninvasive monitoring by means of fluorescence. Present approaches consider
      usually a 1D problem, a simple photochemical process, or a spatially homogeneous
      photosensitizer. In this work, a radially resolved superficial photosensitizer
      fluorescence and 3D photochemical time-dependent PDT model are presented. The
      model provides a time-dependent estimation of tissue fluorescence and the
      photosensitizer and singlet oxygen 3D concentrations. The model is applied to a
      basal cell carcinoma treated by Metvix topical photosensitizer protocol. The
      analysis shows the potentiality in treatment planning and monitoring. The
      fluorescence results are in agreement with previous measurements. 

PMID- 24686621
TI  - Thirteen watt all-fiber mid-infrared supercontinuum generation in a single mode
      ZBLAN fiber pumped by a 2 MUm MOPA system.
AB  - All-fiber-integrated mid-infrared (mid-IR) supercontinuum (SC) generation in a
      single mode ZBLAN (ZrF4-BaF2-LaF3-AlF3-NaF) fiber with 13 W average output power
      and a spectrum extending from ~1.9 to 4.3 MUm is reported, which we believe is
      the highest output power for mid-IR SC generation in ZBLAN fibers. The overall
      optical conversion efficiency from the 790 nm pump light of the last stage Tm
      doped fiber (TDF) amplifier to the total SC output was 20%, and the SC power for
      wavelengths longer than 2.5 MUm was 6.85 W with a power ratio of 52.69% with
      respect to the total SC power. The mid-IR SC generation in ZBLAN fiber was pumped
      by a 2 MUm master oscillator power amplifier (MOPA) system, which is also very
      appropriate for high power 2-2.5 MUm region SC generation. We also demonstrate
      high efficiency SC generation in the TDF amplifier with 62.1 W average power,
      39.8% optical efficiency, and a spectrum extending from 1.9 to 2.7 MUm.

PMID- 24686622
TI  - Hollow antiresonant fibers with reduced attenuation.
AB  - An improved design for hollow antiresonant fibers (HAFs) is presented. It
      consists of adding extra antiresonant glass elements within the air cladding
      region of an antiresonant hollow-core fiber. We use numerical simulations to
      compare fiber structures with and without the additional cladding elements in the
      near- and mid-IR regimes. We show that realizable fiber structures can provide
      greatly improved performance in terms of leakage and bending losses compared to
      previously reported antiresonant fibers. At mid-IR wavelengths, the adoption of
      this novel fiber design will lead to HAFs with reduced bending losses. In the
      near-IR, this design could lead to the fabrication of HAFs with very low
      attenuation. 

PMID- 24686623
TI  - Spectrally resolved incoherent holography: 3D spatial and spectral imaging using
      a Mach-Zehnder radial-shearing interferometer.
AB  - Spatial and spectral information holds the key for characterizing incoherently
      illuminated or self-luminous objects, as well as for imaging fluorescence. We
      propose spectrally resolved incoherent holography using a multifunctional Mach
      Zehnder interferometer that can introduce both a radial shear and a variable time
      delay between the interfering optical fields and permits the measurement of both
      spatial and temporal coherence functions, from which a 3D spatial and spectral
      image of the object is reconstructed. We propose and demonstrate the accurate 3D
      imaging of the object spectra by in situ calibration. 

PMID- 24686624
TI  - Photo-isomerization fronts in dye-doped nematic liquid crystals.
AB  - An experimental study of the photo-isomerization dynamics in dye-doped nematic
      crystals is reported, which shows that, when the sample is illuminated by a
      Gaussian beam, and for high enough input power, a transition from the nematic to
      the isotropic phase takes place in the illuminated area. The two phases are
      spatially connected via a front propagating outward from the center of the beam
      and following the local intensity profile and thus inducing a photo-controlled
      optical aperture. The optical intensity and temperature fields on the sample
      follow the same dynamical profile. The front dynamics is described by a
      phenomenological bi-stable model with an inhomogeneous control parameter,
      directly related to the beam intensity profile. 

PMID- 24686626
TI  - Counting rate enhancements in superconducting nanowire single-photon detectors
      with improved readout circuits.
AB  - Counting rates of superconducting nanowire single-photon detectors are usually
      estimated at hundreds of MHz by their kinetic-inductive reset time. This maximum
      is also limited by capacitor coupling effects in conventional readout circuits.
      In this Letter, we design and demonstrate an improved readout circuit that
      reduces the reset time and removes circuit limits. The counting rate at the 3 dB
      compression point is increased by four times for a large active area detector. We
      also discuss nonlinear dependences of the counting rate on the incident
      continuous-wave optical power and give a numerical model to explain our
      observations.

PMID- 24686627
TI  - Formaldehyde laser-induced fluorescence imaging with a multi-band transmission
      filter.
AB  - A method for laser-induced fluorescence (LIF) imaging of formaldehyde (CH2O) that
      discriminates against the interfering signal from polycyclic aromatic
      hydrocarbons (PAHs) is presented. This technique uses an interference filter with
      11 transmission bands that closely match the most prominent fluorescence features
      of CH2O upon excitation at 355 nm. The signal increases by a factor of 12 with
      the multi-band filter compared to a single-band filter. Slight angle-tuning of
      the filter shifts the transmission maxima to the minima in between the CH2O-LIF
      features. The pixel-by-pixel difference between the images collected at the two
      filter angles thus provides CH2O images free of PAH interference, providing the
      capability for selective single-pulse CH2O-LIF imaging in engine combustion even
      under fuel-rich conditions.

PMID- 24686625
TI  - Ball/dumbbell-like structured micrometer-sized Sb2S3 particles as a scattering
      layer in dye-sensitized solar cells.
AB  - To improve the light harvesting efficiency in dye-sensitized solar cells (DSSC)
      the light scattering layer is important. In this Letter, we present ball/dumbbell
      like structured micrometer-sized Sb2S3 particles for photon propagation in DSSCs
      and demonstrate their effective usage in photoelectrodes. The analysis of the
      photoelectrode by a UV-vis spectrophotometer indicates that the absorption
      wavelength of an electrode with scattering layer can be obviously promoted from
      ultraviolet to visible light. The synthesized Sb2S3 particle structures were also
      characterized by x-ray diffraction, scanning electron microscopy, and
      transmission electron microscopy. The photovoltaic performance of the
      ball/dumbbell-like structured Sb2S3 based cell exhibits excellent power
      conversion efficiency.

PMID- 24686628
TI  - Realization of laterally nondispersing ultrabroadband Airy pulses.
AB  - We present the measurements of the spatiotemporal impulse response of a system
      creating nondispersing Airy pulses, i.e., ultrabroadband Airy beams whose main
      lobe size remains constant over propagation. A custom refractive element with a
      continuous surface profile was used to impose the cubic phase on the input beam.
      The impulse response of the Airy pulse generator was spatiotemporally
      characterized by applying a white-light spatial-spectral interferometry setup
      based on the SEA TADPOLE technique. The results were compared with the
      theoretical model and previously spatiotemporally characterized Airy pulses
      generated by a spatial light modulator. 

PMID- 24686629
TI  - Correlation between multiple modulation instability side lobes in dispersion
      oscillating fiber.
AB  - We investigate numerically and experimentally the spectral correlation between
      multiple modulation instability (MI) side lobes in a dispersion oscillating
      fiber. By leveraging the dispersive Fourier transformation, we acquire
      instantaneous spectra and investigate the energy correlation between individual
      MI sidebands through scattergrams. We found that conjugate MI side lobes are
      strongly correlated while other combinations experience a very low degree of
      correlation, revealing that parametric processes related to each side lobe pair
      act quasi-independently. 

PMID- 24686630
TI  - Far-detuned mid-infrared frequency conversion via normal dispersion modulation
      instability in chalcogenide microwires.
AB  - We report the observation of modulation instability (MI) in the mid-infrared (mid
      IR) spectral region by pumping a hybrid polymer-chalcogenide optical microwire
      with a femtosecond optical parametric oscillator operating at 2.6 MUm. It is
      further shown that this MI occurs in the normal dispersion regime through
      negative fourth-order dispersion and leads to far-detuned parametric frequency
      conversion at 2 and 3.5 MUm, despite the presence of a strong absorption band
      around 2.8 MUm. Stochastic nonlinear Schrodinger equation simulations of mid-IR
      MI are in excellent agreement with experiments.

PMID- 24686631
TI  - Super-resolution imaging using a camera array.
AB  - The angular resolution of many commercial imaging systems is limited, not by
      diffraction or optical aberrations, but by pixilation effects. Multiaperture
      imaging has previously demonstrated the potential for super-resolution (SR)
      imaging using a lenslet array and single detector array. We describe the
      practical demonstration of SR imaging using an array of 25 independent commercial
      off-the-shelf cameras. This technique demonstrates the potential for increasing
      the angular resolution toward the diffraction limit, but without the limit on
      angular resolution imposed by the use of a single detector array. 

PMID- 24686632
TI  - Reflection characteristics of guided-mode resonance filter combined with bottom
      mirror.
AB  - A new type of mirror, based on guided-mode resonance, was proposed and discussed
      to provide a mirror having high reflectance and large wavelength dependence of
      reflection phase variation. The proposed mirror consists of a surface grating
      integrated in a channel waveguide on a high-reflection layer. A SiO2-based device
      was fabricated for 0.85-MUm wavelength operation, and reflection phase variation
      of almost pi, with wavelength change of sub-nanometers, was confirmed
      experimentally.

PMID- 24686634
TI  - Self-referenced frequency comb measurement by using a polarization line-by-line
      pulse shaper.
AB  - A polarization line-by-line pulse shaper is used for generation and noniterative
      spectral phase retrieval of optical arbitrary waveforms (OAWs) spanning over the
      entire repetition period. The method is completely reference-free, making it
      particularly attractive in measuring high repetition-rate OAW. 

PMID- 24686635
TI  - Femtosecond laser ablation of microstructures in fiber and application in
      magnetic field sensing.
AB  - A novel (to our knowledge) 3D microstructure manufactured by a femtosecond laser
      in fiber Bragg grating (FBG) fiber cladding is proposed. The special spiral
      parameters including single thread and double thread with certain pitches of 60
      and 80 MUm are controlled by the feed and rotation speed of a rotary fixture.
      Moreover, supermagnetostrictive TbDyFe film with a thickness of nearly 6 MUm is
      deposited on microgrooves of a FBG by magnetron sputtering technology to form the
      magnetic field sensing probe. Experimental results demonstrate that a FBG with a
      double-thread microstructure has a sensitivity of 1.1  pm/mT responding to a
      magnetic field, and in a theoretical situation, it is approximately six times
      higher than the original optical fiber grating (approximately 0.2  pm/mT). This
      new microstructure and method show great prospect in the magnetic field sensing
      domain.

PMID- 24686633
TI  - Experimental and simulation study of the wavelength dependent second harmonic
      generation of collagen in scattering tissues.
AB  - We report on the wavelength dependence of second harmonic generation (SHG) of
      collagen in scattering tissues over the wavelength range of 800-1200 nm. The
      study incorporates inclusion of the molecular hyperpolarizability beta of
      collagen and optical scattering, both of which are wavelength dependent. Using 3D
      SHG imaging and Monte Carlo simulations, we find the wavelength dependence of
      beta is not well described by a two-state model based on known absorption bands.
      We further find that longer wavelength excitation is inefficient as the reduction
      in scattering is overcome by the decreased beta far from resonance and the
      optimal excitation is within the 800-900 nm range. The impact is larger for
      backward collected SHG.

PMID- 24686636
TI  - Ultracompact optical modulator based on graphene-silica metamaterial.
AB  - We present an ultracompact electro-optic modulator with a length of 15 nm by
      utilizing a permittivity-tunable metamaterial channel, which is composed of
      alternative layers of graphene and silica. Optical waves can propagate through
      the metamaterial channel only if its permittivity is tuned to be near zero. The
      finite-difference time-domain (FDTD) simulations show the insertion loss is
      roughly -0.27  dB while the 3 dB extinction ratio is obtained with a 0.8 V gate
      voltage. The device's footprint is as small as 0.01 MUm2. This modulator consumes
      low power and can potentially be ultrafast.

PMID- 24686637
TI  - CROW bottles.
AB  - A coupled resonator optical waveguide (CROW) bottle is a bottle-shaped nonuniform
      distribution of resonator and coupling parameters. This Letter solves the inverse
      problem for a CROW bottle, i.e., develops a simple analytical method that
      determines a CROW with the required group delay and dispersion characteristics.
      In particular, the parameters of CROWs exhibiting the group delay with zero
      dispersion (constant group delay) and constant dispersion (linear group delay)
      are found. 

PMID- 24686638
TI  - Recording and reconstruction of vector fields in a Fe-doped LiNbO3 crystal.
AB  - We propose a flexible method to record and reconstruct vector fields with space
      variant polarization distribution in c-cut Fe-doped LiNbO3, based on
      photorefractive two-wave mixing. To our knowledge, this is the first approach for
      the reconstruction of vector fields without using the photoinduced anisotropy of
      the recording material.

PMID- 24686639
TI  - Toward a miniature endomicroscope: pixelation-free and diffraction-limited
      imaging through a fiber bundle.
AB  - A fiber bundle is widely used for endoscopic imaging due to its direct image
      delivery capability. However, there exists an inevitable pixelation artifact,
      which limits spatial resolution to the diameter of individual fibers. In this
      Letter, we present a method that can eliminate this artifact and achieve
      diffraction-limited spatial resolution. We exploited the binary control of a
      digital micromirror device to measure a transmission matrix of a fiber bundle and
      to subsequently control mode mixing among individual fibers. In doing so, we
      achieved a 22 kHz scanning rate of a diffraction-limited focused spot and
      obtained fluorescence endoscope imaging (58 MUm * 58 MUm) with near video-rate
      (10.3 Hz) acquisition. Our study lays a foundation for developing an ultrathin
      and high-resolution microendoscope.

PMID- 24686640
TI  - Computed tomography using broadband Bessel THz beams and phase contrast.
AB  - We present new results demonstrating the capability of performing computed
      tomography (CT) using broadband Bessel terahertz (THz) beams. Nondiffractive
      beams such as these exhibit propagation-invariant lines of focus with an extended
      depth-of-field compared to conventional Gaussian beams. Using this property, we
      demonstrate a considerable improvement in the 3D reconstruction image of a
      synthetic sample through the backprojection algorithm. Only when THz Bessel beams
      are used, a full reconstruction of the object structure is made. Moreover, we use
      phase-contrast mechanism which improves the spatial resolution and reconstructed
      images. Our results highlight the potential in using nondiffractive Bessel beams
      to significantly improve 3D-image reconstruction of THz CT. 

PMID- 24686641
TI  - Orbital angular momentum of optical vortices from power measurements and the
      cross-correlation function.
AB  - We show that the complex-amplitude cross-correlation function between two beams
      can be obtained by the global Stokes parameters. We apply this approach to
      determine the topological charge of a Laguerre-Gaussian (LG) beam by performing
      power measurements only. Additionally, we study the connection of the cross
      correlation function with the degree of polarization for nonuniformly polarized
      beams, and we obtain closed-form expressions of the cross correlation for LG
      vector modes and the generalized full Poincare beams. 

PMID- 24686642
TI  - Integrated ytterbium-Raman fiber amplifier.
AB  - An integrated ytterbium-Raman fiber amplifier architecture is proposed for power
      scaling of a Raman fiber laser. It is an ytterbium (Yb) fiber amplifier seeded
      with a double or multiple wavelength laser and followed by a passive Raman fiber.
      The bluest wavelength light gets amplified in the Yb fiber and the power is
      transferred to redder wavelengths in the following Raman fiber. A proof of
      principle experiment demonstrates a 300 W all-fiber linearly polarized single
      mode amplifier at 1120 nm with an optical efficiency of 70%, limited only by
      available pump power. The amplifier consists of 4 m of Yb-doped fiber and 20 m of
      germanium-doped fiber, and seeded with a laser emitting at 1070 and 1120 nm. The
      power evolution of the 1070 and 1120 nm light inside the amplifier is
      investigated, both numerically and experimentally. The possibility of power
      scaling to over kilowatt levels is discussed.

PMID- 24686643
TI  - 10 GHz electro-optical OR/NOR directed logic device based on silicon micro-ring
      resonators.
AB  - We report the demonstration of an OR/NOR directed logic device, which consists of
      two cascaded micro-ring resonators (MRRs) modulated through electric-field
      induced carrier depletion in reverse-biased PN junctions embedded in the ring
      waveguides. The resonance wavelength mismatch between the two nominally identical
      MRRs, caused by fabrication error, is compensated by thermal tuning. Two high
      speed electrical signals applied to the PN junctions act as the operands, and the
      logical operation results are represented by the optical powers detected at the
      two output ports of the device. The working parameters of the device, including
      the working wavelength, the voltage applied to the micro-heater, and the voltages
      applied to the two PN junctions are extracted from the static response spectra of
      the device. Dynamic experimental results show that the OR/NOR logical operations
      can be achieved at the speed of 10 GHz. 

PMID- 24686644
TI  - Diffuse reflectivity measurement using cubic cavity.
AB  - A method for measuring diffuse reflectivity using cubic cavity based on the
      variable port fraction method was developed by measuring oxygen P11 line at 762
      nm using tunable diode laser absorption spectroscopy. An experimental method to
      determine the additional path length l0 was presented. We measured the diffuse
      reflectivity of a cubic cavity with scattering coatings of different thickness.
      The error of diffuse reflectivity was reduced from 0.004 to 0.0003 when the
      diffuse reflectivity increased from 0.867(4) to 0.9887(3). A simulation result
      manifests that the error of diffuse reflectivity has the potential to be further
      reduced at higher diffuse reflectivity.

PMID- 24686645
TI  - Manipulation of linearly polarized states in a diode-pumped YAG/Tm:YAG/YAG bulk
      laser.
AB  - We experimentally demonstrated the manipulation of 2 MUm linearly polarized
      states in a diode-pumped YAG/Tm:YAG/YAG laser with high polarization extinction
      ratio of 28 dB for the very first time to the best of our knowledge. A stable
      linearly polarized state of 2 MUm was achieved without using any specific
      intracavity optical polarization-selected elements. The unexpected phenomenon of
      tunable linear polarization directions was observed. Multidistinct linear
      polarization directions were experimentally obtained, including the peculiar case
      of switchable orthogonally linear polarization directions.

PMID- 24686646
TI  - Heterodyne displacement interferometer, insensitive for input polarization.
AB  - Periodic nonlinearity (PNL) in displacement interferometers is a systematic error
      source that limits measurement accuracy. The PNL of coaxial heterodyne
      interferometers is highly influenced by the polarization state and orientation of
      the source frequencies. In this Letter, we investigate this error source and
      discuss two interferometer designs, designed at TU Delft, that showed very low
      levels of PNL when subjected to any polarization state and/or polarization
      orientation. In the experiments, quarter-wave plates (qwps) and half-wave plates
      (hwps) were used to manipulate the polarization state and polarization
      orientation, respectively. Results from a commercial coaxial system showed first
      order PNL exceeding 10 nm (together with higher order PNL) when the system ceased
      operation at around +/-15 degrees   hwp rotation or +/-20 degrees   qwp rotation.
      The two "Delft interferometers," however, continued operation beyond these maxima
      and obtained first-order PNLs in the order of several picometers, without showing
      higher order PNLs. The major advantage of these interferometers, beside their
      high linearity, is that they can be fully fiber coupled and thus allow for a
      modular system buildup.

PMID- 24686647
TI  - Efficient multiline nanosecond pulse amplification in planar waveguide CO2
      amplifier for extreme UV laser-produced plasma source.
AB  - In this Letter, we report on recent experimental results of a short pulse
      amplification at 10.6 MUm wavelength required to drive a tin laser-produced
      plasma (LPP) extreme ultraviolet (UV) source. We report for the first time, to
      our best knowledge, a highly efficient pulsed amplification in a multipass
      amplifier built on RF-discharge-excited, diffusion-cooled CO2, planar waveguide
      industrial CO2 laser. About 2 kW of output average power was obtained from about
      100 W input average power in ~15  ns pulses at 100 kHz pulse repetition
      frequency. As much as 60% relative extraction efficiency, as compared to
      continuous-wave amplification in similar conditions, and 5.8% wall-plug
      efficiency was recorded and believed to be the highest reported so far. An
      improvement of extraction efficiency by ~10% is reported when driving the
      amplifier with two lines of CO2 regular band in good agreement with expectations.

PMID- 24686648
TI  - Steerable optical antennas by selective heating.
AB  - Directional steerability can be obtained for an array of optical antennas through
      selective heating of the individual elements. Heating changes electrical
      conductivity of the heated element, which affects the phase of the generated
      currents. The variation in temperature can be obtained by modifying the biasing
      point of the individual elements of the array, which would allow fast
      reconfiguration. The numerical evaluation of the performance of an array of a
      reduced number of antennas (2 and 3) shows the feasibility of this approach. 

PMID- 24686649
TI  - Tuning response range of a transmission-based fiber-optic refractometer through
      LP11 mode.
AB  - A kind of sensing scheme is theoretically proposed to efficiently tune the
      response range of a fiber-optic refractometer based on the adiabatic transmission
      of the higher-order LP11 mode. Near the cut-off condition, transmission of the
      LP11 mode is a strong function of the refractive index (RI) under detection; thus
      high sensitivity is achieved. The cut-off RI value is dependent on the waist
      diameter; therefore the response RI range with high sensitivity can be changed
      just by altering the waist diameter. Theoretical calculations reveal that the
      response range is effectively tuned from 1.43-1.438 to 1.35-1.365 when the waist
      diameter is reduced from 2.5 to 1 MUm. The proposed fiber-optic sensor is also
      superior when used as an absorbing sensor since the higher-order mode LP11 has a
      much larger power fraction in the evanescent field compared with the fundamental
      mode LP01 of the same fiber.

PMID- 24686651
TI  - Orbital angular moment of a partially coherent beam propagating through an
      astigmatic ABCD optical system with loss or gain.
AB  - We derive the general expression for the orbital angular momentum (OAM) flux of
      an astigmatic partially coherent beam carrying twist phase [i.e., twisted
      anisotropic Gaussian-Schell model (TAGSM) beam] propagating through an astigmatic
      ABCD optical system with loss or gain. The evolution properties of the OAM flux
      of a TAGSM beam in a Gaussian cavity or propagating through a cylindrical thin
      lens are illustrated numerically with the help of the derived formula. It is
      found that we can modulate the OAM of a partially coherent beam by varying the
      parameters of the cavity or the orientation angle of the cylindrical thin lens,
      which will be useful in some applications, such as free-space optical
      communications and particle trapping. 

PMID- 24686650
TI  - Comparison of laser induced thermal fracture between polycrystalline ceramic and
      crystal Nd:YAG.
AB  - Continuous wave 808 nm pump laser-induced thermal damage of polycrystalline
      transparent ceramic and crystalline Nd:YAG materials was investigated both
      experimentally and theoretically. The measured temperature agrees well with the
      theoretical simulation, and the maximum hoop stresses occur on the incident facet
      of the end-pumped rod at about ?2 times of the pump beam radius w0, where the
      temperature gradient is the highest and the damage occurs first at this location.
      The fracture-limited laser intensity of ceramics was experimentally measured to
      be 6.4+/-0.6  kW/cm2, nearly 64% higher than that of the crystals (3.9+/-0.3 
      kW/cm2). The deduced thermal fracture stress for ceramic was 386+/-50  MPa, which
      is 64% higher than that of the crystals (235+/-16  MPa).

PMID- 24686652
TI  - Daytime measurements of atmospheric temperature profiles (2-15 km) by lidar
      utilizing Rayleigh-Brillouin scattering.
AB  - In this Letter, we report on a novel method for measuring atmospheric temperature
      profiles by lidar during daytime for heights of 2-15.3 km, with a vertical
      resolution of 0.3-2.2 km, using Rayleigh-Brillouin scattering. The measurements
      are performed by scanning a laser (lambda=355 nm) over a 12 GHz range and using a
      Fabry-Perot interferometer as discriminator. The temperature is derived by using
      a new analytical line shape model assuming standard atmospheric pressure
      conditions. Two exemplary temperature profiles resulting from measurements over
      14 and 27 min are shown. A comparison with radiosonde temperature measurements
      shows reasonable agreement. In cloud-free conditions, the temperature difference
      reaches up to 5 K within the boundary layer, and is smaller than 2.5 K above. The
      statistical error of the derived temperatures is between 0.15 and 1.5 K.

PMID- 24686653
TI  - Mode conversion and coupling in a slanted grating.
AB  - We have proposed a novel transmission slanted grating at the central wavelength
      of 1550 nm, which can be used in optical communication. We have presented an
      approximate analytical expression that provides an insightful physical
      description of the simplified modal method for the slanted grating. The odd
      grating mode, which only exists in the asymmetric structure under normal
      incidence, plays the positive role of enhancing the -1st order diffraction
      efficiency. The analytic expressions of mode conversion and coupling can be
      obtained to explain the asymmetric field distribution, which cannot occur in the
      rectangular grating region. Numerical results achieved by the rigorous wave
      analysis verify the validity of the simplified modal method. We expect that the
      theoretical modal method set forth in this work will be helpful for the
      tremendous potential application of the slanted grating.

PMID- 24686654
TI  - Reduction of residual amplitude modulation to 1 * 10-6 for frequency modulation
      and laser stabilization.
AB  - Active control and cancellation of residual amplitude modulation (RAM) in phase
      modulation of an optical carrier is one of the key technologies for achieving the
      ultimate stability of a laser locked to an ultrastable optical cavity.
      Furthermore, such techniques are versatile tools in various frequency modulation
      based spectroscopy applications. In this Letter we report a simple and robust
      approach to actively stabilize RAM in an optical phase modulation process. We
      employ a waveguide-based electro-optic modulator (EOM) to provide phase
      modulation and implement an active servo with both DC electric field and
      temperature feedback onto the EOM to cancel both the in-phase and quadrature
      components of the RAM. This technique allows RAM control on the parts-per-million
      level where RAM-induced frequency instability is comparable to or lower than the
      fundamental thermal noise limit of the best available optical cavities. 

PMID- 24686655
TI  - Generation of optical vortices by using spiral phase plates made of polarization
      dependent devices.
AB  - A method to construct spiral phase plates (SPPs) from quarter-wave plates and
      spatially variable half-wave plates (SVHWPs) is proposed. Optical vortices were
      experimentally generated by using SPPs made of polarization-dependent devices.
      The topological charge of the optical vortex can be also determined by the
      structure of the SVHWP and the polarization of the incident beam. 

PMID- 24686656
TI  - Azimuthally and radially polarized light in conical diffraction.
AB  - Azimuthal and radial polarization states of light are used to produce conical
      diffraction (CD) from a KGd(WO4)2 crystal. The patterns produced in the ring
      plane in each case display marked differences than those seen when linearly
      polarized incident light is used, with the production of a splitting of the CD
      ring into two concentric rings of equal intensity. The free space evolution for
      each type of polarization state is also experimentally recorded and investigated.
      Comparison with theory shows agreement with the experimentally observed results.

PMID- 24686657
TI  - Lateral shearing interferometer with variable shearing for measurement of a small
      beam.
AB  - A lateral shearing interferometer with variable shearing for measurement of a
      small beam is proposed. The interferometer is composed of a polarization beam
      splitter, a thick birefringent plate, a quarter-wave plate, a mirror, and an
      image sensor. The shearing amount can be tiny by using the thick birefringent
      plate as the shear generator. The shearing amount of the interferometer can be
      continuously adjusted by rotating the thick birefringent plate, and 2D
      interferograms can be obtained by rotating the thick birefringent plate along the
      mutually perpendicular directions. The optical path difference is compensated
      with a double lateral shearing by using a quarter-wave plate and a mirror. The
      interferometer is verified by simulation and experiment; the experiment result is
      well coincident with the simulation result. The usefulness of the interferometer
      is verified. 

PMID- 24686658
TI  - Quantitative phase microscopy with off-axis optical coherence tomography.
AB  - We have developed a modality for quantitative phase imaging within spectral
      domain optical coherence tomography based on using an off-axis reference beam. By
      tilting the propagation of the reference beam relative to that of the sample
      beam, a spatially varying fringe is generated. Upon detection of this fringe
      using a parallel spectral domain scheme, the fringe can be used to separate the
      interference component of the signal and obtain the complex sample field. In
      addition to providing quantitative phase measurements within a depth resolved
      measurement, this approach also allows elimination of the complex conjugate
      artifact, a known limitation of spectral interferometry. The principle of the
      approach is described here along with demonstration of its capabilities using
      technical samples. 

PMID- 24686659
TI  - Ultraviolet C upconversion fluorescence of trivalent erbium in BaGd2ZnO5 phosphor
      excited by a visible commercial light-emitting diode.
AB  - Multiple ultraviolet (UV) emission bands have been obtained in Er3+ doped
      BaGd2ZnO5 phosphor under the excitation of a 532 nm solid-state laser, and the
      emission peaks at 217, 254, 278, 296, 314, 348, 374 and 394 nm were determined to
      stem from the high-energy states 4D(1/2), 4D(7/2), 2H(9/2), 2P(1/2), 2P(3/2),
      4G(7/2), 4G(11/2), 4H(9/2) of trivalent erbium, respectively. Some UV emission
      bands in the UVC region can be observed when the sample was excited by commercial
      green (529 nm) and blue (460 nm) LED. In view of the small size, low-drive
      voltage and price of LED, UVC upconversion phosphor BaGd2ZnO5:Er3+ excited by
      visible LED has potential application in environmental sciences.

PMID- 24686660
TI  - Programmable wavelength-tunable second-order optical temporal differentiator
      based on a linearly chirped fiber Bragg grating and a digital thermal controller.
AB  - We proposed and experimentally demonstrated an all-fiber structured wavelength
      tunable second-order optical temporal differentiator based on a linearly chirped
      fiber Bragg grating and a digital-controlled thermal array. The central frequency
      of the differentiation can be reconfigured from 192.141 to 192.616 THz by a
      programmable circuit. In the experiment, a second-order differentiator with 3 dB
      bandwidth of 0.086 THz is achieved with a root mean square error of 4.89%.

PMID- 24686661
TI  - Two-color optically synchronized ultrashort pulses from a Tm/Yb-co-doped fiber
      amplifier.
AB  - A method of producing high quality, optically synchronized two-color ultrashort
      pulses in an active thulium-doped fiber is proposed. We show that sech-shaped
      femtosecond pulses with essentially different wavelengths can be generated
      directly from a Tm/Yb-co-doped amplifier: one pulse at about 2 MUm and the second
      pulse with a tunable wavelength up to 2.3 MUm, which covers the pump and gain
      regions of Cr:ZnSe and Cr:ZnS amplifiers. The shortest pulses with durations of
      145 fs at 2.25 MUm and 125 fs at 2 MUm were measured by the FROG (frequency
      resolved optical gating) technique.

PMID- 24686662
TI  - Steerable optical tweezers for ultracold atom studies.
AB  - We report on the implementation of an optical tweezer system for controlled
      transport of ultracold atoms along a narrow, static confinement channel. The
      tweezer system is based on high-efficiency acousto-optic deflectors and offers
      two-dimensional control over beam position. This opens up the possibility for
      tracking the transport channel when shuttling atomic clouds along it,
      forestalling atom spilling. Multiple clouds can be tracked independently by time
      shared tweezer beams addressing individual sites in the channel. The deflectors
      are controlled using a multichannel direct digital synthesizer, which receives
      instructions on a submicrosecond time scale from a field-programmable gate array.
      Using the tweezer system, we demonstrate sequential binary splitting of an
      ultracold 87Rb cloud into 2(5) clouds.

PMID- 24686664
TI  - Fully switchable multiwavelength fiber laser assisted by a random mirror.
AB  - A real-time switchable and reconfigurable multiwavelength laser has been
      experimentally carried out. The laser cavity is based on a random distributed
      mirror and a novel real-time reconfigurable filter mirror structure. The proposed
      laser has been demonstrated to generate any combination of wavelengths at the 50
      and 100 GHz International Telecommunications Union (ITU) grids specifications. By
      simultaneously using Er-doped fiber and Raman amplification, a 15 nm wide lasing
      window at the C band can be utilized to create up to 18 different lasing
      wavelengths into the ITU grid that can be switched automatically and in real time
      when desired.

PMID- 24686663
TI  - Diffractive catheter for ultrahigh-resolution spectral-domain volumetric OCT
      imaging.
AB  - We present a novel design for an endoscopic imaging catheter utilizing
      diffractive optics for ultrahigh-resolution optical coherence tomography (OCT)
      imaging at 800 nm. A diffractive microlens was developed to alleviate severe
      chromatic aberration when a broadband light source was employed at the 800 nm
      wavelength range. Combined with a home-built fiber rotary joint and a broadband
      Ti:sapphire laser, the imaging catheter achieved a lateral resolution of 6.2 MUm
      and an axial resolution of 3.0 MUm in air. The performance of the catheter was
      demonstrated by three-dimensional full-circumferential endoscopic OCT imaging of
      guinea pig esophagus in vivo.

PMID- 24686665
TI  - Spatial frequency doubling with two-step technique.
AB  - The phenomenon of spatial frequency doubling generated by a two-step technique
      with the collimated beam at normal incidence in the second exposure is presented.
      Theoretical analysis demonstrates that the phenomenon is induced by the Talbot
      effect in photoresist and the superposition of two exposures, and the minimum
      achievable period of the grating with double spatial frequency can be close to
      one half of the exposure wavelength in vacuum, divided by the refractive index of
      photoresist lambda/2n. The two-step technique has the potential to be a simpler
      and more practical resolution-improving technique for the Talbot-effect-based
      approach of spatial frequency doubling. 

PMID- 24686666
TI  - Characteristics of surface plasmon polaritons at a chiral-metal interface.
AB  - The characteristics of surface plasmon polaritons at a chiral-metal interface are
      analyzed in detail. Compared to conventional surface plasmon waves at a
      dielectric-metal interface, it is shown that chiral surface plasmon waves have
      distinguishing features such as the presence of an s-wave at the metal surface,
      the existence of a cutoff frequency and chirality value, and the dependence of
      the propagation length on the chiral parameter. These properties of chiral
      surface plasmon waves can be exploited for on-chip chiral sensing and
      enantiometric detection applications. 

PMID- 24686667
TI  - Voxel model for evaluation of a three-dimensional display and reconstruction in
      integral imaging.
AB  - An approximate voxel model for integral imaging is proposed by ray tracing. By
      analyzing the case of corresponding pixels overlapping completely and partially
      in the image space, the voxel is defined with an appropriate approximation, and
      the voxel size and its distribution feature in imaging space are derived. The
      model is verified in a reconstruction experiment of a resolution target and
      compared with the calculation result of an integral imaging display or
      reconstruction system. The proposed model is simple and easy to calculate and
      thus useful for the evaluation and optimization of integral imaging systems. 

PMID- 24686668
TI  - Independent light fields generated using a phase-only spatial light modulator.
AB  - We present a method of reshaping light in three dimensions via phase modulation.
      The method calculates the target computer-generated hologram individually and
      adds to it an appropriate transfer function to translate the reconstruction to
      any location in space. We are able to simultaneously generate independently
      controlled arbitrary patterns at different positions using a single laser beam. 

PMID- 24686669
TI  - Characterization of a photochromic intraocular lens.
AB  - We demonstrate an optical setup for characterization of a photochromic
      intraocular lens and present first measurement results of the kinetic properties
      and relative spectral transmittance of this photochromic lens. The lens showed a
      main absorption spectrum with a center wavelength of lambda(c)=405 nm and a
      minimum relative transmission of 74% in the activated state. The coloring and
      bleaching times were within the manufacturer-provided specification of
      approximately 10 s for coloring and 30 s for bleaching.

PMID- 24686670
TI  - Dual-coded compressive hyperspectral imaging.
AB  - This Letter presents a new snapshot approach to hyperspectral imaging via dual
      optical coding and compressive computational reconstruction. We demonstrate that
      two high-speed spatial light modulators, located conjugate to the image and
      spectral plane, respectively, can code the hyperspectral datacube into a single
      sensor image such that the high-resolution signal can be recovered in
      postprocessing. We show various applications by designing different optical
      modulation functions, including programmable spatially varying color filtering,
      multiplexed hyperspectral imaging, and high-resolution compressive hyperspectral
      imaging. 

PMID- 24686671
TI  - Liquid crystal high-resolution optically addressed spatial light modulator using
      a nanodimensional chalcogenide photosensor.
AB  - The fabrication and performance of an optically addressed spatial light modulator
      (OASLM) based on nematic liquid crystal and nanodimensional amorphous arsenic
      trisulfide (a-As2S3) chalcogenide glassy films are described. The photoconductive
      a-As2S3 layers are used both as photoalignment material and as a photosensor. The
      use of the OASLM as a color converter is demonstrated in the transmission mode.
      The phase retardation dynamic range is over 3pi. Diffraction efficiency
      measurements show a high resolution (150 lp/mm at 50% MTF). A wide variety of
      materials from the chalcogenide glass (ChG) family are useful for simple
      fabrication of high-resolution OASLMs depending on the desired wavelength.

PMID- 24686672
TI  - 3.77 MUm fiber laser based on cascaded Raman gain in a chalcogenide glass fiber.
AB  - Laser emission is demonstrated at a wavelength of 3.766 MUm in a cascaded Raman
      gain device. The laser cavity is made of two nested pairs of fiber Bragg gratings
      inscribed in a 2.8 m length of low-loss As2S3 fiber. An erbium-doped fluoride
      glass quasi-CW fiber laser emitting at 3.005 MUm is used to pump the cascaded
      Raman cavity, which converts the pump wavelength successively to the first and
      second Stokes orders, respectively at 3.340 and 3.766 MUm. A laser output peak
      power in excess of 100 mW is obtained with a lasing efficiency of about 8.3% with
      respect to the launched pump power. This represents the highest emission
      wavelength delivered by a fiber laser operating at room temperature.

PMID- 24686673
TI  - Midinfrared frequency combs from coherent supercontinuum in chalcogenide and
      optical parametric oscillation.
AB  - We observe the coherence of the supercontinuum generated in a nanospike
      chalcogenide-silica hybrid waveguide pumped at 2 MUm. The supercontinuum is shown
      to be coherent with the pump by interfering it with a doubly resonant optical
      parametric oscillator (OPO) that is itself coherent with the shared pump laser.
      This enables coherent locking of the OPO to the optically referenced pump
      frequency comb, resulting in a composite frequency comb with wavelengths from 1
      to 6 MUm.

PMID- 24686674
TI  - 3 GHz, watt-level femtosecond Raman soliton source.
AB  - We demonstrate a 3 GHz repetition rate, femtosecond Raman soliton source with its
      wavelength tunable from 1.15 to 1.35 MUm. We investigate the dependence of Raman
      soliton formation on different photonic-crystal fibers (PCFs), input powers, and
      fiber lengths. To produce a Raman soliton peaking at the same wavelength, shorter
      PCFs demand higher input average powers and consequently generate stronger Raman
      soliton pulses. Using 30 cm PCF NL-3.2-945, the resulting Raman soliton pulse at
      1.35 MUm has 0.9 W average power. The integrated relative intensity noise of the
      Raman soliton pulse at 1.35 MUm generated from the 54-cm PCF NL-3.2-945 is as low
      as 0.33% from 100 Hz to 10 MHz.

PMID- 24686675
TI  - Conical light sword optical beam and its healing property.
AB  - A new diffractive optical element, named as a conical light sword optical
      element, is presented. In the focal volume, this element produces a helical
      amplitude profile that can be used as an optical twister. We have experimentally
      demonstrated the optical healing property of the conical light sword optical beam
      (CLSOB). This healing property comes from the transverse helical energy flow, due
      to the evolution of multiple unipolar vortices in the propagation of CLSOB. We
      envisage that this spiral intensity profile and optical healing property of the
      beam find potential applications in propagation through a scattering and
      turbulent media, imaging with extended depth of field, and in optical tweezers. 

PMID- 24686676
TI  - Room temperature Bloch surface wave polaritons.
AB  - Polaritons are hybrid light-matter quasi-particles that have gathered a
      significant attention for their capability of showing room temperature and out-of
      equilibrium Bose-Einstein condensation. More recently, a novel class of ultrafast
      optical devices have been realized by using flows of polariton fluids, such as
      switches, interferometers, and logical gates. However, polariton lifetimes and
      propagation distances are strongly limited by photon losses and accessible in
      plane momenta in normal microcavity samples. In this work, we show experimental
      evidence of the formation of room temperature propagating polariton states
      arising from the strong coupling between organic excitons and a Bloch surface
      wave. This result, which was only recently predicted, paves the way for the
      realization of polariton devices that could allow lossless propagation up to
      macroscopic distances. 

PMID- 24686677
TI  - Larger-area single-mode photonic crystal surface-emitting lasers enabled by an
      accidental Dirac point.
AB  - By altering the lattice geometry of the photonic crystal (PhC) surface-emitting
      lasers (PCSELs), we tune the regular lasing band edges of quadratic dispersions
      to form a single accidental Dirac point of linear dispersion at the Brillouin
      zone center. This not only increases the mode spacing by orders of magnitude but
      also eliminates the distributed in-plane feedback to enable single-mode PCSELs of
      substantially larger area and thus substantially higher output power. The
      advantages of using accidental Dirac cones are systematically evaluated through
      two-dimensional in-plane calculations and confirmed by three-dimensional
      simulations of PhC slab devices. 

PMID- 24686678
TI  - Photonic crystal fiber half-taper probe based refractometer.
AB  - A compact single-mode photonic crystal fiber single-mode fiber tip (SPST)
      refractive index sensor is demonstrated in this Letter. A CO2 laser cleaving
      technique is utilized to provide a clean-cut fiber tip, which is then coated by a
      layer of gold to increase reflection. An average sensitivity of 39.1 nm/RIU and a
      resolvable index change of 2.56*10(-4) are obtained experimentally with a ~3.2
      MUm diameter SPST. The temperature dependence of this fiber-optic sensor probe is
      presented. The proposed SPST refractometer is also significantly less sensitive
      to temperature and an experimental demonstration of this reduced sensitivity is
      presented in the Letter. Because of its compactness, ease of fabrication, linear
      response, low temperature dependency, easy connectivity to other fiberized
      optical components and low cost, this refractometer could find various
      applications in chemical and biological sensing.

PMID- 24686679
TI  - Generation of a vector doughnut beam from an internal mirror He-Ne laser.
AB  - We demonstrate the direct generation of a vector doughnut mode from an internal
      mirror He-Ne laser using the spot defect method. A circular-shaped spot defect of
      ~30 MUm in diameter with low reflectivity created on the inner surface of a
      cavity mirror by laser ablation suppressed the oscillation of a Gaussian beam
      resulting in the oscillation of a doughnut beam. Polarization investigation
      showed that the generated beam was a vector hybrid mode.

PMID- 24686680
TI  - Ermakov-Lewis symmetry in photonic lattices.
AB  - We present a class of waveguide arrays that is the classical analog of a quantum
      harmonic oscillator, where the mass and frequency depend on the propagation
      distance. In these photonic lattices, refractive indices and second-neighbor
      couplings define the mass and frequency of the analog quantum oscillator, while
      first-neighbor couplings are a free parameter to adjust the model. The quantum
      model conserves the Ermakov-Lewis invariant, thus the photonic crystal also
      possesses this symmetry. 

PMID- 24686681
TI  - Enhancing spatial resolution in digital holographic microscopy by biprism
      structured illumination.
AB  - A novel and efficient architecture of a structured-illumination digital
      holographic microscope (DHM) is presented. As the DHM operates at the diffraction
      limit, its spatial resolution on label-free imaging of transparent samples is
      improved by illuminating the sample with a structured illumination produced by a
      Fresnel's biprism. The theoretical analysis of the method forecasts a twofold
      improvement of the spatial resolution. The proposed method requires only two
      images to improve the spatial resolution, which eases the process of unmixing the
      high-resolution components by means of an unknown phase-shift procedure.
      Numerical modeling and experimental results validate the theoretical findings. 

PMID- 24686682
TI  - Video-rate computational heterodyne holography.
AB  - We present a versatile computational image rendering software of optically
      acquired holograms. The reported software can process 4 Megapixel 8-bit raw
      frames from a sensor array acquired at a sustained rate of 80 Hz. Video-rate
      image rendering is achieved by streamline image processing with commercial
      computer graphics hardware. For time-averaged holograms acquired in off-axis
      optical configuration with a frequency-shifted reference beam, wide-field imaging
      of one tunable spectral component is permitted. This software is validated by
      phase-stepped hologram rendering, and noncontact monitoring of surface acoustic
      waves by single and dual sideband hologram rendering. It demonstrates the
      suitability of holography for video-rate computational laser Doppler imaging in a
      heterodyne optical configuration.

PMID- 24686683
TI  - Photonic crystal slab fabricated on the platform of lithium niobate-on-insulator.
AB  - We report on a photonic crystal slab patterned on a 690 nm thick LiNbO3 thin film
      bonded to SiO2 on lithium niobate substrate. The transmission spectrum is
      measured and a broad and clear photonic bandgap ranging from 1335 to 1535 nm with
      a maximum extinction ratio of more than 20 dB is observed. The bandgap is
      simulated by plane wave expansion and 3D finite-difference time-domain methods.
      Such a deep and broad bandgap structure can be used to form high-performance
      photonic devices and circuits on the platform of lithium niobate-on-insulator.

PMID- 24686684
TI  - Diffuse photon density wavefront speed as a contrast for tomographic imaging of
      heterogeneous diffusive media.
AB  - An imaging algorithm is implemented for tomographically reconstructing contrast
      maps of the space variant speed of diffuse photon density wavefronts (DPDWFs)
      propagating in biological tissue-like diffusing media. This speed serves as a
      novel contrast not previously exploited in the literature. The algorithm employs
      early photon arrival times (EPATs) extracted from a set of time domain
      measurements. A relationship between EPATs and the speed of DPDWFs is exploited
      as the forward model. The forward model and its use in an inverse problem are
      supported by experimental results. These are carried out for 3D media with tissue
      like optical properties. The resulting inverse problem is formulated as a set of
      algebraic equations and solved within a constrained linear least squares
      framework. The results indicate that the algorithm provides tomographic
      information on heterogeneities locations and distributions. 

PMID- 24686685
TI  - Characteristics of the single-longitudinal-mode planar-waveguide external cavity
      diode laser at 1064 nm.
AB  - We describe the characteristics of the planar-waveguide external cavity diode
      laser (PW-ECL). To the best of our knowledge, it is the first butterfly-packaged
      1064 nm semiconductor laser that is stable enough to be locked to an external
      frequency reference. We evaluated its performance from the viewpoint of precision
      experiments. Using a hyperfine absorption line of iodine, we suppressed its
      frequency noise by a factor of up to 10(4) at 10 mHz. The PW-ECL's compactness
      and low cost make it a candidate to replace traditional Nd:YAG nonplanar ring
      oscillators and fiber lasers in applications that require a single longitudinal
      mode.

PMID- 24686686
TI  - Tunable deep ultraviolet single-longitudinal-mode laser generated with Ba(1-x)B(2
      y-z)O4Si(x)Al(y)Ga(z) crystal.
AB  - We report a new nonlinear crystal, Ba(1-x)B(2-y-z)O4Si(x)Al(y)Ga(z), and employ
      it to a compact 1 kHz single-longitudinal-mode Ti:Sapphire master oscillator
      power amplifier system for fourth harmonic generation. A maximum output power of
      130 mW is obtained in the tunable range of 195-205 nm with linewidth of less than
      0.1 pm.

PMID- 24686687
TI  - Generation of 1.5 MUm discrete frequency-entangled two-photon state in
      polarization-maintaining fibers.
AB  - In this Letter, the generation of a 1.5 MUm discrete frequency-entangled two
      photon state is realized based on a piece of commercial polarization-maintaining
      fiber (PMF). It is connected with a polarization beam splitter to realize a
      modified Sagnac fiber loop (MSFL). Correlated two-photon states are generated
      through a spontaneous four-wave-mixing process along the two propagation
      directions of the MSFL, and output from the MSFL with orthogonal polarizations.
      Their quantum interference is realized through a 45 degrees  polarization
      collimation between polarization axes of PMFs inside and outside the MSFL, while
      their phase difference is controlled by the polarization state of the pump light.
      The frequency-entangled property of the two-photon state is demonstrated by a
      spatial quantum beating experiment with a fringe visibility of 98.2+/-1.3%,
      without subtracting the accidental coincidence counts. The proposed scheme
      generates a 1.5 MUm discrete frequency-entangled two-photon state in a
      polarization-maintaining way, which is desired in practical quantum light
      sources.

PMID- 24686688
TI  - Transformation optics scheme for two-dimensional materials.
AB  - Two-dimensional optical materials, such as graphene, can be characterized by
      surface conductivity. So far, the transformation optics schemes have focused on
      three-dimensional properties such as permittivity epsilon and permeability MU. In
      this Letter, we use a scheme for transforming surface currents to highlight that
      the surface conductivity transforms in a way different from epsilon and MU. We
      use this surface conductivity transformation to demonstrate an example problem of
      reducing the scattering of the plasmon mode from sharp protrusions in graphene. 

PMID- 24686689
TI  - Fully motorized optical-resolution photoacoustic microscopy.
AB  - We have developed fully motorized optical-resolution photoacoustic microscopy (OR
      PAM), which integrates five complementary scanning modes and simultaneously
      provides a high imaging speed and a wide field of view (FOV) with 2.6 MUm lateral
      resolution. With one-dimensional (1D) motion-mode mechanical scanning, we
      measured the blood flow through a cross section of a blood vessel in vivo. With
      two-dimensional (2D) optical scanning at a laser repetition rate of 40 kHz, we
      achieved a 2 kHz B-scan rate over a range of 50 MUm with 20 A-lines and 50 Hz
      volumetric-scan rate over a FOV of 50  MUm * 50  MUm with 400 A-lines, which
      enabled real-time tracking of cellular dynamics in vivo. With synchronized 1D
      optical and 2D mechanical hybrid scanning, we imaged a 10  mm * 8  mm FOV within
      three minutes, which is 20 times faster than the conventional mechanical scan in
      our second-generation OR-PAM. With three-dimensional mechanical contour scanning,
      we maintained the optimal signal-to-noise ratio and spatial resolution of OR-PAM
      while imaging objects with uneven surfaces, which is essential for quantitative
      studies.

PMID- 24686690
TI  - High-sensitivity strain sensor based on in-fiber improved Fabry-Perot
      interferometer.
AB  - We demonstrated a high-sensitivity strain sensor based on an in-fiber Fabry-Perot
      interferometer (FPI) with an air cavity, which was created by splicing together
      two sections of standard single-mode fibers. The sensitivity of this strain
      sensor was enhanced to 6.0  pm/MUepsilon by improving the cavity length of the
      FPI by means of repeating arc discharges for reshaping the air cavity. Moreover,
      such a strain sensor has a very low temperature sensitivity of 1.1  pm/ degrees
      C, which reduces the cross sensitivity between tensile strain and temperature.

PMID- 24686691
TI  - Experimental excitation of the Dyakonov-Tamm wave in the grating-coupled
      configuration.
AB  - The Dyakonov-Tamm wave was experimentally excited along the periodically
      corrugated interface of magnesium fluoride as the isotropic homogeneous
      partnering material and a zinc-selenide chiral sculptured thin film (STF) as the
      anisotropic and periodically nonhomogeneous partnering material. The total
      transmittance of a p-polarized 633 nm laser beam was measured as a function of
      the angle of incidence for several thicknesses of the chiral STF to identify
      those dips in total transmittance that are indicative of the excitation of a
      Dyakonov-Tamm wave.

PMID- 24686692
TI  - Accelerating diffraction-free beams in photonic lattices.
AB  - We study nondiffracting accelerating paraxial optical beams in periodic
      potentials, in both the linear and the nonlinear domains. In particular, we show
      that only a unique class of z-dependent lattices can support a true accelerating
      diffractionless beam. Accelerating lattice solitons, autofocusing beams and
      accelerating bullets in optical lattices are systematically examined. 

PMID- 24686693
TI  - Stable, self-starting, passively mode-locked fiber ring laser of the 3 MUm class.
AB  - We report a passively mode-locked Ho(3+)Pr(3+)-doped fluoride fiber laser,
      producing 6 ps pulses at a repetition rate of 24.8 MHz, with a peak power of 465
      W. For the first time, a ring cavity was demonstrated in a fluoride fiber laser
      arrangement which was essential to the generation of stable and self-starting
      mode-locked pulses.

PMID- 24686694
TI  - General analytic solution for far-field phase and amplitude control, with a phase
      only spatial light modulator.
AB  - We present an analytical solution for the phase introduced by a phase-only
      spatial light modulator to generate far-field phase and amplitude distributions
      within a domain of interest. The solution is demonstrated experimentally and
      shown to enable excellent control of the far-field amplitude and phase. 

PMID- 24686696
TI  - Widely tunable second-harmonic generation in a chalcogenide-tellurite hybrid
      optical fiber.
AB  - When a chalcogenide-tellurite hybrid optical fiber with a high refractive index
      difference Deltan=0.24 is pumped by an optical parametric oscillator with a pump
      wavelength from 1700 to 3000 nm, widely tunable second-harmonic generation (SHG)
      from 850 to 1502 nm is obtained. The observation of SHG is primarily due to the
      surface nonlinearity polarization at the core-cladding interface and the second
      harmonic signal remains stable at the maximal level throughout the laser pulse
      irradiation.

PMID- 24686695
TI  - High-efficiency B4C/Mo2C alternate multilayer grating for monochromators in the
      photon energy range from 0.7 to 3.4 keV.
AB  - An alternate multilayer (AML) grating has been prepared by coating an ion etched
      lamellar grating with a B4C/Mo2C multilayer (ML) having a layer thickness close
      to the groove depth. Such a structure behaves as a 2D synthetic crystal and can
      reach very high efficiencies when the Bragg condition is satisfied. This AML
      coated grating has been characterized at the SOLEIL Metrology and Tests Beamline
      between 0.7 and 1.7 keV and at the four-crystal monochromator beamline of
      Physikalisch-Technische Bundesanstalt (PTB) at BESSY II between 1.75 and 3.4 keV.
      A peak diffraction efficiency of nearly 27% was measured at 2.2 keV. The measured
      efficiencies are well reproduced by numerical simulations made with the
      electromagnetic propagation code CARPEM. Such AML gratings, paired with a matched
      ML mirror, constitute efficient monochromators for intermediate energy photons.
      They will extend the accessible energy for many applications as x-ray absorption
      spectroscopy or x-ray magnetic circular dichroism experiments.

PMID- 24686697
TI  - Compact tunable multibandpass filters based on liquid-filled photonic crystal
      fibers.
AB  - We demonstrated a compact tunable multibandpass filter with a short size of about
      9 mm and a high wavelength-tuning sensitivity of up to -2.194  nm/ degrees C by
      means of filling a liquid with a high refractive index of 1.700 into the air
      holes of a photonic crystal fiber (PCF). Such a PCF-based filter maintains an
      almost constant bandwidth and a large extinction ratio of more than 40 dB within
      the whole wavelength tuning range of more than 100 nm. Moreover, the transmission
      spectrum of the PCF-based filter is insensitive to the stretch force and the
      curvature of the fiber.

PMID- 24686698
TI  - Improved idler beam quality via simultaneous parametric oscillation and signal-to
      idler conversion.
AB  - We report on an improvement of idler beam quality in a singly resonant optical
      parametric oscillator (OPO), where the resonant signal is converted to the idler
      via an additional difference frequency generation (DFG) process. The two
      processes are phase matched simultaneously by a quasi-periodically poled
      nonlinear crystal. Whereas back-conversion of the signal and idler to the pump
      frequency distorts the idler beam in a standard OPO, in a quasi-periodic OPO the
      DFG process reduces the signal intensity, leading to suppression of back
      conversion and, hence, improvement in idler beam quality. Indeed, the
      experimental results show under the same pump power a significant improvement in
      idler beam quality for the quasi-periodic OPO (1<=M2<=2.1) as compared with the
      standard OPO (3.2<=M2<=5.3).

PMID- 24686700
TI  - Scintillations of higher-order laser beams in non-Kolmogorov medium.
AB  - In an atmospheric medium that shows a non-Kolmogorov turbulence behavior, the
      variation of the on-axis scintillation index is evaluated when higher-order laser
      modes are used as the excitation. The Rytov method is employed together with the
      equivalent structure constant, which makes our results valid in weak turbulence.
      In the limiting case, our solution correctly reduces to the known scintillation
      index of the Gaussian beam in Kolmogorov turbulence. For all the higher-order
      even modes, increase in the power law exponent, alpha of the non-Kolmogorov
      spectrum is found to increase the scintillations. When the source size of the
      higher-order modes is large, higher-order even modes attain almost the same
      scintillation index values for all alpha. However, for small source sizes, being
      valid for any realization of the non-Kolmogorov spectrum, the scintillations
      decrease as the mode order becomes large. The changes in the propagation
      distance, structure constant, and the wavelength do not vary these trends. 

PMID- 24686699
TI  - DBR and DFB lasers in neodymium- and ytterbium-doped photothermorefractive
      glasses.
AB  - The first demonstration, to the best of our knowledge, of distributed Bragg
      reflector (DBR) and monolithic distributed feedback (DFB) lasers in
      photothermorefractive glass doped with rare-earth ions is reported. The lasers
      were produced by incorporation of the volume Bragg gratings into the laser gain
      elements. A monolithic single-frequency solid-state laser with a linewidth of 250
      kHz and output power of 150 mW at 1066 nm is demonstrated.

PMID- 24686701
TI  - Direct holographic imaging of ultrafast laser damage process in thin films.
AB  - Dynamic process of femtosecond laser-induced damage formation in dielectric thin
      films is reconstructed from a series of time-resolved images. Ta2O5 single-layer
      coatings of four different thicknesses have been investigated in transmission
      mode by means of time-resolved off-axis digital holography. Different processes
      overlapped in time were found to occur; namely, the Kerr effect, free-electron
      generation, ultrafast lattice heating, and shockwave generation. The trends in
      contribution of these effects are qualitatively reproduced by numerical models
      based on electron-rate equations and Drude theory, which take into account
      transient changes in the films and interference effects of the pump and probe
      pulses.

PMID- 24686702
TI  - Multicore fiber with rectangular cross-section.
AB  - We have fabricated, to our knowledge, the first rectangular cross-section
      multicore fiber with eight cores arranged in a line. We have shown that the
      rectangular cross-section remains practically unchanged during the fiber-drawing
      process. The heterogeneous version of the proposed fiber design could be
      beneficial for crosstalk reduction because of the low influence of fiber bends on
      crosstalk between neighboring cores. 

PMID- 24686704
TI  - Breathing solitary-pulse pairs in a linearly coupled system.
AB  - It is shown that pairs of solitary pulses (SPs) in a linearly coupled system with
      opposite group velocity dispersions form robust breathing bound states. The
      system can be realized by temporal-modulation coupling of SPs with different
      carrier frequencies propagating in the same medium, or by coupling of SPs in a
      dual-core waveguide. Broad SP pairs are produced in a virtually exact form by
      means of the variational approximation. Strong nonlinearity tends to destroy the
      periodic evolution of the SP pairs. 

PMID- 24686703
TI  - Optimized asymmetrical tangent phase mask to obtain defocus invariant modulation
      transfer function in incoherent imaging systems.
AB  - Wavefront coding as an optical-digital hybrid imaging technique can be used to
      extend the depth of field. The key to wavefront coding lies in the design of
      suitable phase masks to achieve the invariant imaging properties over a wide
      range of defocus. In this Letter, we propose another phase mask with a tangent
      function to enrich the odd symmetrical kind of phase masks. The performance of
      the tangent phase mask is evaluated by comparison with a cubic mask, improved-1
      logarithmic mask, improved-2 logarithmic mask, and sinusoidal mask. The results
      demonstrate that the tangent phase mask has superior performance in extending the
      depth of field. 

PMID- 24686705
TI  - Interleaved and partial transmission interleaved optical coherent orthogonal
      frequency division multiplexing.
AB  - A novel group of interleaved orthogonal frequency division multiplexing (IL-OFDM)
      and partial transmission IL-OFDM (PT-IL-OFDM) schemes are proposed for optical
      coherent detection. In the interleaved operation, the odd (or even) subcarriers
      of an OFDM symbol are reserved (closed). Such an interleaved arrangement can gain
      the tolerance toward phase noise induced interchannel interference (PN-ICI).
      Meanwhile, the peak to average power ratio (PAPR) of an OFDM signal can be
      significantly reduced. However, half of the capacity is sacrificed for the
      interleaved operation. By exploring the time domain symmetry property of IL-OFDM,
      the concept of PT-IL-OFDM is proposed to double the capacity of IL-OFDM.
      Consequently, PT-IL-OFDM can gain the merits of low PAPR and a high tolerance
      toward PN-ICI without capacity sacrifice. Numerical simulation verified the
      advanced properties of IL-OFDM and PT-IL-OFDM. 

PMID- 24686706
TI  - Improving characteristics of Faraday isolators based on TAG ceramics by cerium
      doping.
AB  - A Faraday isolator (FI) based on a new magneto-optical medium-Ce:TAG ceramics-has
      been fabricated and studied in experiments. Compensation of thermally induced
      depolarization in the FI increases the isolation ratio from 31 to 39 dB at the
      laser power of 300 W. Estimates predict stable operation of the device with
      kilowatt laser power.

PMID- 24686707
TI  - Diode-pumped 1988-nm Tm:YAP laser mode-locked by intracavity second-harmonic
      generation in periodically poled LiNbO3.
AB  - We report a diode-pumped intracavity second-harmonic generation mode-locked solid
      state Tm:YAP laser operating at 1988 nm using a periodically poled congruent
      LiNbO3 as the nonlinear crystal. The threshold of continuous wave mode locking is
      11.6 W. The maximum output power is 1.67 W, while the shortest pulse obtained is
      4.7 ps at a repetition rate of 97.09 MHz.

PMID- 24686708
TI  - 1 W single-frequency Tm-doped ZBLAN fiber MOPA around 810 nm.
AB  - We demonstrate a tunable narrow-linewidth fiber MOPA system around 810 nm for the
      light source of the Sr optical lattice clock. The coherent cw light source with a
      wavelength of 813.42 nm was generated by a combination of a narrow linewidth
      external-cavity laser diode and a Tm-doped ZBLAN fiber amplifier, which was
      upconversion-pumped by an Yb-doped fiber laser at 1064 nm. The maximum output
      power of 1.1 W was obtained with the launched power of 17 W, which is the highest
      power obtained from a Tm-doped fiber amplifier ever reported.

PMID- 24686709
TI  - Programmable multi-wavelength filter with Mach-Zehnder interferometer embedded in
      ethanol filled photonic crystal fiber.
AB  - We experimentally demonstrated a free spectrum range (FSR) tunable comb filter
      based on a programmable thermo-controlled Mach-Zehnder interferometer. The device
      is constructed by sandwiching a length of ethanol-filled photonic crystal fiber
      between single-mode fibers. A digital thermal printer head is used to facilitate
      the interference as well as to adjust the phase difference by selectively
      activating the independent heating elements, thus the FSR can be digitally tuned
      conveniently. The filter shows a feature of periodic equalized passbands with
      flat-top steep-edge as well as a high extinction ratio over a very wide range of
      wavelengths from 1.52 to 1.58 MUm.

PMID- 24686710
TI  - Absolute frequency stabilization of an extended-cavity diode laser by means of
      noise-immune cavity-enhanced optical heterodyne molecular spectroscopy.
AB  - We implemented an optical frequency standard based on noise-immune cavity
      enhanced optical heterodyne molecular spectroscopy (NICE-OHMS) at 1.39 MUm. The
      emission frequency of an extended-cavity diode laser was actively stabilized
      against the center of the 4(4,1)->4(4,0) transition of the H(2)(18)O nu1+nu3
      band, under optical saturation conditions. The nonlinear regime of laser-gas
      interaction was reached by using an optical cavity with a finesse of about 8700.
      By filling it with an 18O-enriched water sample at a pressure of a few Pa, the
      Lamb dip could be observed with a full width at half-maximum of about 2 MHz.
      Absolute frequency stabilization was obtained by locking the cavity resonance to
      the center of the sub-Doppler signal, which was provided by the NICE-OHMS
      technique under the dispersion regime of operation. An Allan deviation analysis
      demonstrated a relative frequency stability of ~5*10(-13) for an integration time
      of 1 s. For longer integration times, the flicker frequency noise floor set the
      stability at the level of 4*10(-14).

PMID- 24686711
TI  - Multiwavelength time-stretch imaging system.
AB  - A high-speed microscopic imaging system based on a multiwavelength source and
      time-stretch technique is proposed and demonstrated. We realize an imaging system
      at 1D scan rate of 80 MHz with 20 resolvable points. This scheme breaks the
      bottleneck of large bandwidth and high repetition rate in mode-lock lasers and
      has great potential for imaging system integration.

PMID- 24686712
TI  - Experimental demonstration of polarization-insensitive air-cladding grating
      couplers for silicon-on-insulator waveguides.
AB  - We present an air-cladding apodized focusing subwavelength grating that can
      effectively couple two polarizations into a single waveguide. For the transverse
      magnetic mode, -3.2  dB maximum coupling efficiency with ~28  nm 1 dB bandwidth
      is achieved. With the same grating, -4.3  dB maximum coupling efficiency with ~58
      nm 1 dB bandwidth is achieved for the transverse electric mode. The minimum
      difference between two polarizations' coupling peaks is demonstrated to be ~32 
      nm. At the 1525 nm wavelength range, the polarization-insensitive grating is
      demonstrated with -6.5  dB coupling efficiency. The polarization-insensitive
      coupling wavelength can be controlled experimentally.

PMID- 24686713
TI  - Tomographic diffractive microscopy of living cells based on a common-path
      configuration.
AB  - We demonstrate a common-path tomographic diffractive microscopy technique for
      three-dimensional (3D) refractive-index (RI) imaging of unstained living cells. A
      diffraction grating is utilized to generate a reference beam that traverses a
      blank region of the sample in a common-path off-axis interferometry setup. Single
      shot phase images captured at multiple illumination angles are used for 3D RI
      reconstruction based on optical diffraction tomography. The common-path
      configuration shows lower temporal phase fluctuations and better RI resolution
      than a Mach-Zehnder configuration. 3D subcellular RI distributions of live HeLa
      cells are quantified. 

PMID- 24686714
TI  - Optimization of in vivo spectroscopic photoacoustic imaging by smart optical
      wavelength selection.
AB  - Spectroscopic photoacoustic (sPA) imaging is an emerging biomedical imaging
      modality which can be used to simultaneously identify multiple optical absorbers
      in tissue. With current technology, the image acquisition time is limited
      primarily by the laser repetition rate, and sPA image acquisition can take
      seconds to minutes, depending on the system and imaging volume. We have developed
      an algorithm that can be used to eliminate extraneous wavelengths and decrease
      image acquisition time while maintaining image quality. Here, we show the effect
      the wavelength selection has on in vivo sPA imaging. As an example, dye draining
      to the lymph node of a mouse was imaged. We demonstrate that sPA image quality is
      more accurately preserved when wavelengths are chosen based on the spectral
      features of the absorbers compared to often-used selection of evenly spaced
      wavelengths. In fact, only three wavelengths are needed to accurately spectrally
      unmix the dye from oxygenated and deoxygenated hemoglobin. 

PMID- 24686715
TI  - Attosecond pulse walk-off in high-order harmonic generation.
AB  - We study the influence of the generation conditions on the group delay of
      attosecond pulses in high-order harmonic generation in gases. The group delay
      relative to the fundamental field is found to decrease with increasing gas
      pressure in the generation cell, reflecting a temporal walk-off due to the
      dispersive properties of the nonlinear medium. This effect is well reproduced
      using an on-axis phase-matching model of high-order harmonic generation in an
      absorbing gas. 

PMID- 24686716
TI  - The relationship between mathematics and language: academic implications for
      children with specific language impairment and English language learners.
AB  - PURPOSE: The present study examined the relationship between mathematics and
      language to better understand the nature of the deficit and the academic
      implications associated with specific language impairment (SLI) and academic
      implications for English language learners (ELLs). METHOD: School-age children (N
      = 61; 20 SLI, 20 ELL, 21 native monolingual English [NE]) were assessed using a
      norm-referenced mathematics instrument and 3 experimental computer-based
      mathematics games that varied in language demands. Group means were compared with
      analyses of variance. RESULTS: The ELL group was less accurate than the NE group
      only when tasks were language heavy. In contrast, the group with SLI was less
      accurate than the groups with NE and ELLs on language-heavy tasks and some
      language-light tasks. Specifically, the group with SLI was less accurate on tasks
      that involved comparing numerical symbols and using visual working memory for
      patterns. However, there were no group differences between children with SLI and
      peers without SLI on language-light mathematics tasks that involved visual
      working memory for numerical symbols. CONCLUSION: Mathematical difficulties of
      children who are ELLs appear to be related to the language demands of mathematics
      tasks. In contrast, children with SLI appear to have difficulty with mathematics
      tasks because of linguistic as well as nonlinguistic processing constraints.

PMID- 24686717
TI  - A reduced graphene oxide supported Cu(3)SnS(4) composite as an efficient visible
      light photocatalyst.
AB  - In this study, a visible light responsive Cu3SnS4/reduced graphene oxide (RGO)
      photocatalyst has been synthesized by a facile one-step solvothermal method. The
      as-synthesized samples were characterized by X-ray diffraction (XRD),
      transmission electron microscopy (TEM), high-resolution transmission electron
      microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS), X-ray
      photoelectron spectroscopy (XPS), Raman spectroscopy, N2 adsorption-desorption,
      UV-vis diffuse reflectance spectra (DRS), and photoluminescence (PL) emission
      spectroscopy. The photocatalytic activity of the Cu3SnS4/RGO composite under
      visible-light irradiation (lambda > 420 nm) was evaluated by measuring the
      degradation of rhodamine B (RhB) and phenol. The results revealed that the
      Cu3SnS4 nanoplates dispersed uniformly on the RGO surface. The Cu3SnS4/RGO
      composite exhibited much higher photocatalytic activity than pure Cu3SnS4. The
      enhancement in photocatalytic activity is likely to be due to the synergistic
      effect of an improved adsorptivity of pollutants, an enhanced visible light
      absorption and an effective charge separation. In addition, the Cu3SnS4/RGO
      photocatalyst was stable during the reaction and could be used repeatedly. 

PMID- 24686718
TI  - Trace fear conditioning in mice.
AB  - In this experiment we present a technique to measure learning and memory. In the
      trace fear conditioning protocol presented here there are five pairings between a
      neutral stimulus and an unconditioned stimulus. There is a 20 sec trace period
      that separates each conditioning trial. On the following day freezing is measured
      during presentation of the conditioned stimulus (CS) and trace period. On the
      third day there is an 8 min test to measure contextual memory. The representative
      results are from mice that were presented with the aversive unconditioned
      stimulus (shock) compared to mice that received the tone presentations without
      the unconditioned stimulus. Trace fear conditioning has been successfully used to
      detect subtle learning and memory deficits and enhancements in mice that are not
      found with other fear conditioning methods. This type of fear conditioning is
      believed to be dependent upon connections between the medial prefrontal cortex
      and the hippocampus. One current controversy is whether this method is believed
      to be amygdala-independent. Therefore, other fear conditioning testing is needed
      to examine amygdala-dependent learning and memory effects, such as through the
      delay fear conditioning. 

PMID- 24686719
TI  - Initiatives to improve feedback culture in the final year of a veterinary
      program.
AB  - Despite the recognized importance of feedback in education, student satisfaction
      with the feedback process in medical and veterinary programs is often
      disappointing. We undertook various initiatives to try to improve the feedback
      culture in the final clinical year of the veterinary program at the University of
      Bristol, focusing on formative verbal feedback. The initiatives included E-mailed
      guidelines to staff and students, a faculty development workshop, and a
      reflective portfolio task for students. Following these initiatives, staff and
      students were surveyed regarding their perceptions of formative feedback in
      clinical rotations, and focus groups were held to further explore issues. The
      amount of feedback appeared to have increased, along with improved recognition of
      feedback by students and increased staff confidence and competence in the
      process. Other themes that emerged included inconsistencies in feedback among
      staff and between rotations; difficulties with giving verbal feedback to
      students, particularly when it relates to professionalism; the consequences of
      feedback for both staff and students; changes and challenges in students'
      feedback-seeking behavior; and the difficulties in providing accurate, personal
      end-of-rotation assessments. This project has helped improve the feedback culture
      within our clinics; the importance of sustaining and further developing the
      feedback culture is discussed in this article. 

PMID- 24686720
TI  - Reconsidering the lecture in modern veterinary education.
AB  - Those teaching in the higher-education environment are now increasingly meeting
      with larger cohorts of students. The result is additional pressure on the
      resources available and on the teacher and learners. Against this backdrop,
      discussions and reflections took place between a practitioner, within a UK
      veterinary school, and an educational researcher with extensive experience in
      observing teaching in veterinary medicine. The result was an examination of the
      lecture as a method of teaching to consider how to resolve identified challenges.
      The focus of much of the literature is on technical aspects of teaching and
      learning, reverting to a range of tips to resolve particular issues recognized in
      large-group settings. We suggest that while these tips are useful, they will only
      take a practitioner so far. To be able to make a genuine connection to learners
      and help them connect directly to the discipline, we need to take account of the
      emotional aspects of our role as teachers, without which, delivery of knowledge
      may be undermined. 

PMID- 24686721
TI  - One-pot hydrothermal synthesis of peony-like Ag/Ag(0.68)V2O5 hybrid as high
      performance anode and cathode materials for rechargeable lithium batteries.
AB  - A peony-like Ag/Ag0.68V2O5 hybrid assembled from nanosheets with the thickness of
      40 nm was synthesized through a one-pot hydrothermal approach from vanadium
      pentoxide (V2O5), oxalic acid (H2C2O4), and silver nitrate (AgNO3) at 180 
      degrees C for 24 h. The hybrid exhibits high performance as both anode and
      cathode materials for rechargeable lithium batteries. Electrochemical
      measurements revealed that the as-prepared Ag/Ag0.68V2O5 hybrid displayed
      excellent cycling stability, especially as an anode material. The resulting anode
      retains 100% of the initial capacity after 1000 cycles under a current density of
      400 mA g(-1). This phenomenon may be attributed to electron conductivity
      improvement by the existence of metallic silver in the hybrid in addition to the
      convenient access to lithium ion ingress/egress because of its unique structure. 

PMID- 24686722
TI  - Do adults with cochlear implants rely on different acoustic cues for phoneme
      perception than adults with normal hearing?
AB  - PURPOSE Several acoustic cues specify any single phonemic contrast. Nonetheless,
      adult, native speakers of a language share weighting strategies, showing
      preferential attention to some properties over others. Cochlear implant (CI)
      signal processing disrupts the salience of some cues: In general, amplitude
      structure remains readily available, but spectral structure less so. This study
      asked how well speech recognition is supported if CI users shift attention to
      salient cues not weighted strongly by native speakers. METHOD Twenty adults with
      CIs participated. The /balpha/-/walpha/ contrast was used because spectral and
      amplitude structure varies in correlated fashion for this contrast. Adults with
      normal hearing weight the spectral cue strongly but the amplitude cue negligibly.
      Three measurements were made: labeling decisions, spectral and amplitude
      discrimination, and word recognition. RESULTS Outcomes varied across listeners:
      Some weighted the spectral cue strongly, some weighted the amplitude cue, and
      some weighted neither. Spectral discrimination predicted spectral weighting.
      Spectral weighting explained the most variance in word recognition. Age of onset
      of hearing loss predicted spectral weighting but not unique variance in word
      recognition. CONCLUSION The weighting strategies of listeners with normal hearing
      likely support speech recognition best, so efforts in implant design, fitting,
      and training should focus on developing those strategies. 

PMID- 24686724
TI  - Production and processing of subject-verb agreement in monolingual Dutch children
      with specific language impairment.
AB  - PURPOSE: In this study, the authors investigated whether errors with subject-verb
      agreement in monolingual Dutch children with specific language impairment (SLI)
      are influenced by verb phonology. In addition, the productive and receptive
      abilities of Dutch acquiring children with SLI regarding agreement inflection
      were compared. METHOD: An SLI group (6-8 years old), an age-matched group with
      typical development, and a language-matched, younger, typically developing (TD)
      group participated in the study. Using an elicitation task, the authors tested
      use of third person singular inflection after verbs that ended in obstruents
      (plosive, fricative) or nonobstruents (sonorant). The authors used a self-paced
      listening task to test sensitivity to subject-verb agreement violations. RESULTS:
      Omission was more frequent after obstruents than nonobstruents; the younger TD
      group used inflection less often after plosives than fricatives, unlike the SLI
      group. The SLI group did not detect subject-verb agreement violations if the
      ungrammatical structure contained a frequent error (omission), but if the
      ungrammatical structure contained an infrequent error (substitution), subject
      verb agreement violations were noticed. CONCLUSIONS: The use of agreement
      inflection by children with TD or SLI is affected by verb phonology. Differential
      effects in the 2 groups are consistent with a delayed development in Dutch SLI.
      Parallels between productive and receptive abilities point to weak lexical
      agreement inflection representations in Dutch SLI.

PMID- 24686723
TI  - Inducing plasticity of astrocytic receptors by manipulation of neuronal firing
      rates.
AB  - Close to two decades of research has established that astrocytes in situ and in
      vivo express numerous G protein-coupled receptors (GPCRs) that can be stimulated
      by neuronally-released transmitter. However, the ability of astrocytic receptors
      to exhibit plasticity in response to changes in neuronal activity has received
      little attention. Here we describe a model system that can be used to globally
      scale up or down astrocytic group I metabotropic glutamate receptors (mGluRs) in
      acute brain slices. Included are methods on how to prepare parasagittal
      hippocampal slices, construct chambers suitable for long-term slice incubation,
      bidirectionally manipulate neuronal action potential frequency, load astrocytes
      and astrocyte processes with fluorescent Ca(2+) indicator, and measure changes in
      astrocytic Gq GPCR activity by recording spontaneous and evoked astrocyte Ca(2+)
      events using confocal microscopy. In essence, a "calcium roadmap" is provided for
      how to measure plasticity of astrocytic Gq GPCRs. Applications of the technique
      for study of astrocytes are discussed. Having an understanding of how astrocytic
      receptor signaling is affected by changes in neuronal activity has important
      implications for both normal synaptic function as well as processes underlying
      neurological disorders and neurodegenerative disease. 

PMID- 24686725
TI  - Cognitive-behavioral therapy for medication-resistant psychosis: a meta-analytic
      review.
AB  - Patients with schizophrenia often continue to experience disabling positive
      symptoms, despite adequate trials of medication. In these situations, patients
      may be prescribed an adjunctive medication, but a more effective choice may be
      cognitive-behavioral therapy (CBT). This review of 16 published articles from 12
      randomized controlled trials found that CBT was associated with robust
      improvements in the positive symptoms of psychotic disorders. In addition, the
      improvements were sustained at follow-up, the authors reported. 

PMID- 24686727
TI  - 2.5D multi-view gait recognition based on point cloud registration.
AB  - This paper presents a method for modeling a 2.5-dimensional (2.5D) human body and
      extracting the gait features for identifying the human subject. To achieve view
      invariant gait recognition, a multi-view synthesizing method based on point cloud
      registration (MVSM) to generate multi-view training galleries is proposed. The
      concept of a density and curvature-based Color Gait Curvature Image is introduced
      to map 2.5D data onto a 2D space to enable data dimension reduction by discrete
      cosine transform and 2D principle component analysis. Gait recognition is
      achieved via a 2.5D view-invariant gait recognition method based on point cloud
      registration. Experimental results on the in-house database captured by a
      Microsoft Kinect camera show a significant performance gain when using MVSM. 

PMID- 24686726
TI  - Activation of Sonic hedgehog signaling in neural progenitor cells promotes glioma
      development in the zebrafish optic pathway.
AB  - Dysregulation of Sonic hedgehog (Shh) signaling has been implicated in glioma
      pathogenesis. Yet, the role of this pathway in gliomagenesis remains
      controversial because of the lack of relevant animal models. Using the
      cytokeratin 5 promoter, we ectopically expressed a constitutively active
      zebrafish Smoothened (Smoa1) in neural progenitor cells and analyzed tumorigenic
      capacity of activated Shh signaling in both transient and stable transgenic fish.
      Transient transgenic fish overexpressing Smoa1 developed retinal and brain
      tumors, suggesting smoa1 is oncogenic in the zebrafish central nervous system
      (CNS). We further established stable transgenic lines that simultaneously
      developed optic pathway glioma (OPG) and various retinal tumors. In one of these
      lines, up to 80% of F1 and F2 fish developed tumors within 1 year of age.
      Microarray analysis of tumor samples showed upregulated expression of genes
      involved in the cell cycle, cancer signaling and Shh downstream targets ptc1,
      gli1 and gli2a. Tumors also exhibited specific gene signatures characteristic of
      radial glia and progenitor cells as transcriptions of radial glia genes cyp19a1b,
      s100beta, blbp, gfap and the stem/progenitor genes nestin and sox2 were
      significantly upregulated. Overexpression of GFAP, S100beta, BLBP and Sox2 was
      confirmed by immunofluorescence. We also detected overexpression of Mdm2
      throughout the optic pathway in fish with OPG, therefore implicating the Mdm2
      Tp53 pathway in glioma pathogenesis. In conclusion, we demonstrate that activated
      Shh signaling initiates tumorigenesis in the zebrafish CNS and provide the first
      OPG model not associated with neurofibromatosis 1. 

PMID- 24686728
TI  - A new approach to integrate Internet-of-things and software-as-a-service model
      for logistic systems: a case study.
AB  - Cloud computing is changing the ways software is developed and managed in
      enterprises, which is changing the way of doing business in that dynamically
      scalable and virtualized resources are regarded as services over the Internet.
      Traditional manufacturing systems such as supply chain management (SCM), customer
      relationship management (CRM), and enterprise resource planning (ERP) are often
      developed case by case. However, effective collaboration between different
      systems, platforms, programming languages, and interfaces has been suggested by
      researchers. In cloud-computing-based systems, distributed resources are
      encapsulated into cloud services and centrally managed, which allows high
      automation, flexibility, fast provision, and ease of integration at low cost. The
      integration between physical resources and cloud services can be improved by
      combining Internet of things (IoT) technology and Software-as-a-Service (SaaS)
      technology. This study proposes a new approach for developing cloud-based
      manufacturing systems based on a four-layer SaaS model. There are three main
      contributions of this paper: (1) enterprises can develop their own cloud-based
      logistic management information systems based on the approach proposed in this
      paper; (2) a case study based on literature reviews with experimental results is
      proposed to verify that the system performance is remarkable; (3) challenges
      encountered and feedback collected from T Company in the case study are discussed
      in this paper for the purpose of enterprise deployment. 

PMID- 24686729
TI  - Quartz-enhanced photoacoustic spectroscopy: a review.
AB  - A detailed review on the development of quartz-enhanced photoacoustic sensors
      (QEPAS) for the sensitive and selective quantification of molecular trace gas
      species with resolved spectroscopic features is reported. The basis of the QEPAS
      technique, the technology available to support this field in terms of key
      components, such as light sources and quartz-tuning forks and the recent
      developments in detection methods and performance limitations will be discussed.
      Furthermore, different experimental QEPAS methods such as: on-beam and off-beam
      QEPAS, quartz-enhanced evanescent wave photoacoustic detection, modulation
      cancellation approach and mid-IR single mode fiber-coupled sensor systems will be
      reviewed and analysed. A QEPAS sensor operating in the THz range, employing a
      custom-made quartz-tuning fork and a THz quantum cascade laser will be also
      described. Finally, we evaluated data reported during the past decade and draw
      relevant and useful conclusions from this analysis. 

PMID- 24686730
TI  - Enhancement of the wear particle monitoring capability of oil debris sensors
      using a maximal overlap discrete wavelet transform with optimal decomposition
      depth.
AB  - Oil debris sensors are effective tools to monitor wear particles in lubricants.
      For in situ applications, surrounding noise and vibration interferences often
      distort the oil debris signature of the sensor. Hence extracting oil debris
      signatures from sensor signals is a challenging task for wear particle
      monitoring. In this paper we employ the maximal overlap discrete wavelet
      transform (MODWT) with optimal decomposition depth to enhance the wear particle
      monitoring capability. The sensor signal is decomposed by the MODWT into
      different depths for detecting the wear particle existence. To extract the
      authentic particle signature with minimal distortion, the root mean square
      deviation of kurtosis value of the segmented signal residue is adopted as a
      criterion to obtain the optimal decomposition depth for the MODWT. The proposed
      approach is evaluated using both simulated and experimental wear particles. The
      results show that the present method can improve the oil debris monitoring
      capability without structural upgrade requirements. 

PMID- 24686731
TI  - A wearable system for gait training in subjects with Parkinson's disease.
AB  - In this paper, a system for gait training and rehabilitation for Parkinson's
      disease (PD) patients in a daily life setting is presented. It is based on a
      wearable architecture aimed at the provision of real-time auditory feedback.
      Recent studies have, in fact, shown that PD patients can receive benefit from a
      motor therapy based on auditory cueing and feedback, as happens in traditional
      rehabilitation contexts with verbal instructions given by clinical operators. To
      this extent, a system based on a wireless body sensor network and a smartphone
      has been developed. The system enables real-time extraction of gait spatio
      temporal features and their comparison with a patient's reference walking
      parameters captured in the lab under clinical operator supervision. Feedback is
      returned to the user in form of vocal messages, encouraging the user to keep
      her/his walking behavior or to correct it. This paper describes the overall
      concept, the proposed usage scenario and the parameters estimated for the gait
      analysis. It also presents, in detail, the hardware-software architecture of the
      system and the evaluation of system reliability by testing it on a few subjects. 

PMID- 24686732
TI  - Aspirin as adjuvant therapy for stage III colon cancer: standard of care?

PMID- 24686733
TI  - Higher prevalence of autoimmune diseases and longer spells of vertigo in patients
      affected with familial Meniere's disease: A clinical comparison of familial and
      sporadic Meniere's disease.
AB  - PURPOSE This study compared clinical features, predisposing factors, and
      concomitant diseases between sporadic and familial Meniere's disease (MD). METHOD
      Retrospective chart review and postal questionnaire were used. Participants were
      250 definite patients with MD (sporadic, n =149; familial, n = 101) who fulfilled
      the American Academy of Otorhinolaryngology-Head and Neck Surgery (1995)
      criteria. RESULTS On average, familial patients were affected 5.6 years earlier
      than sporadic patients, and they suffered from significantly longer spells of
      vertigo (p = .007). The prevalence of rheumatoid arthritis (p = .002) and other
      autoimmune diseases (p = .046) was higher among the familial patients, who also
      had more migraine (p = .036) and hearing impairment (p = .002) in their families.
      CONCLUSION The clinical features of familial and sporadic MD are very similar in
      general, but some differences do exist. Familial MD patients are affected earlier
      and suffer from longer spells of vertigo.

PMID- 24686734
TI  - A novel oxidative procedure for the synthesis of benzamides from styrenes and
      amines under metal-free conditions.
AB  - An interesting procedure for the oxidative synthesis of amides from styrenes and
      amines has been developed. Various primary amides were formed in moderate yields
      (25-81%). Secondary amides can be produced in moderate yields as well (41-68%).
      Notably, no transition metal catalyst was needed for this transformation. This is
      the first example of oxidative transformation of styrenes to benzamides. 

PMID- 24686735
TI  - Speech, sign, or multilingualism for children with hearing loss: quantitative
      insights into caregivers' decision making.
AB  - PURPOSE: The authors sought to investigate the influence of a comprehensive range
      of factors on the decision making of caregivers of children with hearing loss
      regarding the use of speech, the use of sign, spoken language multilingualism,
      and spoken language choice. This is a companion article to the qualitative
      investigation described in Crowe, Fordham, McLeod, and Ching (2014). METHOD:
      Through a questionnaire, 177 caregivers of 157 Australian children with hearing
      loss (ages 3;5 to 9;4 [years;months], Mage = 6;6) rated the importance of a range
      of potential influences on their decision making regarding their children's
      communication. The majority of children were reported to use speech (96.6%) as
      part or all of their communication system, with fewer children reported to use
      sign (20.9%). Few children used more than one spoken language (8.3%). RESULTS:
      Proportional analyses and exploratory factor analyses were conducted. Overall,
      caregivers' decisions were influenced by their children's audiological and
      intervention characteristics, communication with those around them, community
      participation, access to intervention and education services in English, and
      concerns about their children's future lives. The advice of speech-language
      pathologists, audiologists, and specialist teachers was more important to
      caregivers than advice from medical practitioners and nonprofessionals.
      CONCLUSION: Caregivers' decision making regarding communication mode and language
      use is influenced by factors that are not equally weighted and that relate to
      child, family, community, and advice from others. Knowledge of these factors can
      assist professionals in supporting caregivers making choices regarding
      communication.

PMID- 24686736
TI  - Corals record long-term Leeuwin current variability including Ningaloo Nino/Nina
      since 1795.
AB  - Variability of the Leeuwin current (LC) off Western Australia is a footprint of
      interannual and decadal climate variations in the tropical Indo-Pacific. La Nina
      events often result in a strengthened LC, high coastal sea levels and unusually
      warm sea surface temperatures (SSTs), termed Ningaloo Nino. The rarity of such
      extreme events and the response of the southeastern Indian Ocean to regional and
      remote climate forcing are poorly understood owing to the lack of long-term
      records. Here we use well-replicated coral SST records from within the path of
      the LC, together with a reconstruction of the El Nino-Southern Oscillation to
      hindcast historical SST and LC strength from 1795 to 2010. We show that
      interannual and decadal variations in SST and LC strength characterized the past
      215 years and that the most extreme sea level and SST anomalies occurred post
      1980. These recent events were unprecedented in severity and are likely aided by
      accelerated global ocean warming and sea-level rise. 

PMID- 24686737
TI  - Can human mannequin-based simulation provide a feasible and clinically acceptable
      method for training tracheostomy management skills for speech-language
      pathologists?
AB  - PURPOSE: Workplace training for tracheostomy management is currently recognized
      to be inconsistent and insufficient. A novel approach, using technology-enhanced
      simulation, may provide a solution to training tracheostomy management skills by
      providing a consistent, time-efficient, and risk-free learning environment. The
      current research evaluated clinicians' tracheostomy skills acquisition after
      training in a simulated learning environment and explored changes in clinicians'
      confidence and perceptions after the experience. METHOD: Forty-two clinicians
      with no or low levels of tracheostomy skill attended one of six, 1-day simulation
      courses. The training involved both part-task skill learning and immersive
      simulated scenarios. To evaluate clinicians' acquisition of manual skills,
      performance of core tasks during the scenarios was assessed by independent
      observers. Questionnaires were used to examine perceived outcomes, benefits, and
      perceptions of the learning environment at pre-, post-, and 4 months post
      training. RESULTS: Only 1 clinician failed to successfully execute all core
      practical tasks. Clinicians' confidence increased significantly ( p < .05) from
      pre- to post-workshop and was maintained to 4 months post-workshop across most
      parameters. All clinicians reported positive perceptions regarding their learning
      outcomes and learning in a simulated environment. CONCLUSION: These findings
      validate the use of simulation as a clinical training medium and support its
      future use in tracheostomy competency-training pathways.

PMID- 24686738
TI  - Immune responses to O-specific polysaccharide and lipopolysaccharide of Vibrio
      cholerae O1 Ogawa in adult Bangladeshi recipients of an oral killed cholera
      vaccine and comparison to responses in patients with cholera.
AB  - Protective immunity to cholera is serogroup specific, and serogrouping is defined
      by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We
      characterized OSP-specific immune responses in adult recipients of an oral killed
      cholera vaccine (OCV WC-rBS) and compared these with responses in patients with
      cholera caused by Vibrio cholerae O1 Ogawa. Although vaccinees developed plasma
      immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC,
      marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination,
      responses were significantly lower than that which occurred after cholera.
      Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG
      memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas
      vaccinees only developed IgG responses to OSP 30 days after the second
      immunization. The markedly lower ASC and MBC responses to OSP and LPS observed
      among vaccinees might explain, in part, the lower protection of an OCV compared
      with natural infection.

PMID- 24686739
TI  - Genetic structure inferred from mitochondrial 12S ribosomal RNA sequence of
      Oncomelania quadrasi, the intermediate snail host of Schistosoma japonicum in the
      Philippines.
AB  - Species and subspecies of the Oncomelania hupensis species complex are recognized
      as intermediate hosts of Schistosoma japonicum. Of these species and subspecies,
      O. quadrasi is distributed throughout the Philippines. This study used 12S
      ribosomal RNA sequences to explore the genetic structure of O. quadrasi
      populations in the Philippines. Three subspecies, O. h. hupensis, O. h.
      formosana, and O. h. chiui of this group were also examined. The phylogenetic
      tree and haplotypes network showed that O. quadrasi separated from the
      subspecies. Ten O. quadrasi haplotypes (Oq1-Oq10) clustered in relation to their
      geographic origin. Genetic differentiation (FST) and estimated gene flow (Nm)
      among populations showed significant differences, ranging from 0.556-1.000 to
      0.00-0.74, respectively. Genetic differences among groups (FCT = 0.466),
      populations within a group (FSC = 0.727), and populations (FST = 0.854) were
      observed. These results indicate that the O. quadrasi populations in the
      Philippines have a substructure associated with their geographic origin. 

PMID- 24686740
TI  - Transmission of Onchocerca volvulus by Simulium neavei in Mount Elgon focus of
      Eastern Uganda has been interrupted.
AB  - The study determined that Simulium neavei-transmitted onchocerciasis in Mount
      Elgon onchocerciasis focus had been interrupted. Annual mass treatment with
      ivermectin changed to two times per year along with vector elimination in 2007.
      Then, baseline microfilaria (mf) prevalence data of 1994 in five sentinel
      communities were compared with follow-up data in 2005 and 2011. Blood spots from
      3,051 children obtained in 2009 were analyzed for Onchocerca volvulus
      immunoglobulin G4 antibodies. Fresh water crab host captures and blackflies
      collected indicated their infestation with larval stages of S. neavei and
      presence or absence of the vector, respectively. Mf rates dropped from 62.2% to
      0.5%, and 1 (0.03%) of 3,051 children was positive for O. volvulus antibodies.
      Crab infestation dropped from 41.9% in 2007 to 0%, and S. neavei biting reduced
      to zero. Both remained zero for the next 3 years, confirming interruption of
      onchocerciasis transmission, and interventions were halted. 

PMID- 24686741
TI  - Antischistosomal versus antiandrogenic properties of aryl hydantoin Ro 13-3978.
AB  - In the early 1980s, the antischistosomal aryl hydantoin Ro 13-3978 (AH01), a
      close structural analogue of the androgen receptor antagonist nilutamide, was
      discovered. Administration of 100 mg/kg oral doses of AH01 to mice infected with
      adult and juvenile Schistosoma mansoni produced 95% and 64% total worm burden
      reductions, confirming its high activity against adult worms, and showing that
      AH01 is also effective against juvenile infections. AH01 had no measureable
      interaction with the androgen receptor in a ligand competition assay, but it did
      block dihydrotestosterone-induced cell proliferation in an androgen-dependent
      human prostate cancer cell line. For AH01, nilutamide, and three closely related
      aryl hydantoin derivatives, there was no correlation between antischistosomal
      activity and androgen receptor interaction. 

PMID- 24686742
TI  - Assessing the performance of CareStart Malaria Pf/Pv Combo Test against thick
      blood film in the diagnosis of malaria in northwest Ethiopia.
AB  - Bivalent rapid diagnostic tests are promising diagnostic tools for Plasmodium
      falciparum and P. vivax. Their diagnostic performance was evaluated against thick
      blood smear to assist national malaria control programs. A cross-sectional study
      was conducted to evaluate the performance of CareStart against thick blood smears
      among 398 acute febrile patients visiting the Felegeselam Health Center in
      December of 2011. Thick blood smears were examined under 100* objectives to
      diagnose Plasmodium species. Similarly, CareStart Malaria Pf/Pv Combo Test was
      performed as per the manufacturer's instruction. The ability of CareStart Malaria
      Pf/Pv Combo Test to diagnose Plasmodium malaria was very good, with 99.8% (95%
      confidence interval = 97.7-100%) sensitivity and 97.7% (95% confidence interval =
      94.6-99.1%) specificity. The sensitivity and specificity of the CareStart Test is
      comparable with the thick blood smear in diagnosing malaria. Hence, it is
      preferable to use the CareStart Malaria Pf/Pv Combo Test instead of microscopy in
      areas where microscopic diagnosis is limited. 

PMID- 24686743
TI  - Identification of risk factors for plague in the West Nile Region of Uganda.
AB  - Plague is an often fatal, primarily flea-borne rodent-associated zoonosis caused
      by Yersinia pestis. We sought to identify risk factors for plague by comparing
      villages with and without a history of human plague cases within a model-defined
      plague focus in the West Nile Region of Uganda. Although rat (Rattus rattus)
      abundance was similar inside huts within case and control villages, contact rates
      between rats and humans (as measured by reported rat bites) and host-seeking flea
      loads were higher in case villages. In addition, compared with persons in control
      villages, persons in case villages more often reported sleeping on reed or straw
      mats, storing food in huts where persons sleep, owning dogs and allowing them
      into huts where persons sleep, storing garbage inside or near huts, and cooking
      in huts where persons sleep. Compared with persons in case villages, persons in
      control villages more commonly reported replacing thatch roofing, and growing
      coffee, tomatoes, onions, and melons in agricultural plots adjacent to their
      homesteads. Rodent and flea control practices, knowledge of plague, distance to
      clinics, and most care-seeking practices were similar between persons in case
      villages and persons in control villages. Our findings reinforce existing plague
      prevention recommendations and point to potentially advantageous local
      interventions. 

PMID- 24686744
TI  - Detection and phylogenetic characterization of a case of Histoplasma capsulatum
      infection in mainland China.
AB  - Histoplasmosis usually occurs in specific endemic areas. Sporadic cases have also
      been reported in mainland China. Here, we described an indigenous case of
      disseminated histoplasmosis. Phylogenetic analysis revealed that the Histoplasma
      capsulatum isolated in our case belongs to the Australian clade. Combined with
      previous studies, it revealed high genetic diversity among Chinese H. capsulatum
      isolates. 

PMID- 24686745
TI  - Measurement Properties of the Low Back Activity Confidence Scale (LoBACS).
AB  - The purpose of this study was to determine the measurement properties of the Low
      Back Activity Confidence Scale (LoBACS) in individuals with post-acute low back
      pain (LBP) receiving nonsurgical intervention, including construct validity,
      factorial validity, and internal consistency reliability. Data were analyzed from
      an existing randomized clinical trial involving 112 patients with LBP. Evidence
      for convergent validity was observed through significant correlations between
      LoBACS subscale scores and other function, pain, and psychobehavioral measures.
      LoBACS subscales accounted for 36% of the unique variance in dependent variable
      measurements, suggesting a satisfactory level of statistical divergence between
      the LoBACS and other psychobehavioral measurements in this study. Cronbach's
      alpha ranged from .88 to .92 for LoBACS subscales, and item-total correlations
      exceeded .6, indicating high internal consistency reliability. Principal axis
      factoring confirmed the hypothesized three-subscale structure by correctly
      classifying 14 of the 15 items. These findings indicate the LoBACS is valid and
      internally consistent to measure domain-specific self-efficacy beliefs.

PMID- 24686746
TI  - Physician Scientist Training in the United States: A Survey of the Current
      Literature.
AB  - The declining number of physician scientists is an alarming issue. A systematic
      review of all existing programs described in the literature was performed, so as
      to highlight which programs may serve as the best models for the training of
      successful physician scientists. Multiple databases were searched, and 1,294
      articles related to physician scientist training were identified. Preference was
      given to studies that looked at number of confirmed publications and/or research
      grants as primary outcomes. Thirteen programs were identified in nine studies.
      Eighty-three percent of Medical Scientist Training Program (MSTP) graduates, 77%
      of Clinician Investigator Training Program (CI) graduates, and only 16% of
      Medical Fellows Program graduates entered a career in academics. Seventy-eight
      percent of MSTP graduates succeeded in obtaining National Institute of Health
      (NIH) grants, while only 15% of Mayo Clinic National Research Service Award-T32
      graduates obtained NIH grants. MSTP physician scientists who graduated in 1990
      had 13.5 +/- 12.5 publications, while MSTP physician scientists who graduated in
      1975 had 51.2 +/- 38.3 publications. Additionally, graduates from the Mayo
      Clinic's MD-PhD Program, the CI Program, and the NSRA Program had 18.2 +/- 20.1,
      26.5 +/- 24.5, and 17.9 +/- 26.3 publications, respectively. MSTP is a successful
      model for the training of physician scientists in the United States, but training
      at the postgraduate level also shows promising outcomes. An increase in the
      number of positions available for training at the postgraduate level should be
      considered. 

PMID- 24686748
TI  - Visualizing neuroblast cytokinesis during C. elegans embryogenesis.
AB  - This protocol describes the use of fluorescence microscopy to image dividing
      cells within developing Caenorhabditis elegans embryos. In particular, this
      protocol focuses on how to image dividing neuroblasts, which are found underneath
      the epidermal cells and may be important for epidermal morphogenesis. Tissue
      formation is crucial for metazoan development and relies on external cues from
      neighboring tissues. C. elegans is an excellent model organism to study tissue
      morphogenesis in vivo due to its transparency and simple organization, making its
      tissues easy to study via microscopy. Ventral enclosure is the process where the
      ventral surface of the embryo is covered by a single layer of epithelial cells.
      This event is thought to be facilitated by the underlying neuroblasts, which
      provide chemical guidance cues to mediate migration of the overlying epithelial
      cells. However, the neuroblasts are highly proliferative and also may act as a
      mechanical substrate for the ventral epidermal cells. Studies using this
      experimental protocol could uncover the importance of intercellular communication
      during tissue formation, and could be used to reveal the roles of genes involved
      in cell division within developing tissues.

PMID- 24686749
TI  - Cultural and demographic factors influencing noise exposure estimates from use of
      portable listening devices in an urban environment.
AB  - PURPOSE: This study examined listening levels and duration of portable listening
      devices (PLDs) used by people with diversity of ethnicity, education, music
      genre, and PLD manufacturer. The goal was to estimate participants' PLD noise
      exposure and identify factors influencing user behavior. METHOD: This study
      measured listening levels of 160 adults in 2 New York City locations: (a) a quiet
      college campus and (b) Union Square, a busy interchange. Participants completed a
      questionnaire regarding demographics and PLD use. Ordinary least squares
      regression was used to explore the significance of demographic and behavioral
      factors. RESULTS: Average listening level was 94.1 dBA, with 99 of 160 (61.9%)
      and 92 of 159 (57.5%) exceeding daily (L A8hn) and weekly (L Awkn) recommended
      exposure limit, respectively. African American participants listened at the
      highest average levels (99.8 dBA). CONCLUSIONS: A majority of PLD users exceeded
      recommended exposure levels. Factors significant for higher exposure were
      ethnicity and age; factors not significantly associated with exposure were
      gender, education, location, awareness of possible association between PLD use
      and noise-induced hearing loss, mode of transportation, device manufacturer, and
      music genre. Efforts to effect behavior changes to lessen noise-induced hearing
      loss risk from PLD use should be sensitive to the cultural differences within the
      targeted population.

PMID- 24686747
TI  - Executive functioning skills in preschool-age children with cochlear implants.
AB  - PURPOSE: The purpose of this study was to determine whether deficits in executive
      functioning (EF) in children with cochlear implants (CIs) emerge as early as the
      preschool years. METHOD: Two groups of children ages 3 to 6 years participated in
      this cross-sectional study: 24 preschoolers who had CIs prior to 36 months of age
      and 21 preschoolers with normal hearing (NH). All were tested on normed measures
      of working memory, inhibition-concentration, and organization-integration.
      Parents completed a normed rating scale of problem behaviors related to EF.
      Comparisons of EF skills of children with CIs were made to peers with NH and to
      published nationally representative norms. RESULTS: Preschoolers with CIs showed
      significantly poorer performance on inhibition-concentration and working memory
      compared with peers with NH and with national norms. No group differences were
      found in visual memory or organization-integration. When data were controlled for
      language, differences in performance measures of EF remained, whereas differences
      in parent-reported problems with EF were no longer significant. Hearing history
      was generally unrelated to EF. CONCLUSIONS: This is the first study to
      demonstrate that EF deficits found in older children with CIs begin to emerge as
      early as preschool years. The ability to detect these deficits early has
      important implications for early intervention and habilitation after cochlear
      implantation.

PMID- 24686751
TI  - Insights into the coordination mode of quercetin with the Al(III) ion from a
      combined experimental and theoretical study.
AB  - Combining potentiometric, spectroscopic and theoretical DFT computations we have
      studied the formation of the Al(iii)-quercetin complex in ethanol solution. The
      possible complexation sites have been considered on the basis of all the
      experimental and theoretical tools used. Results supported proposing a 1 : 1
      neutral complex and the possibility to have different isomers in solution. 

PMID- 24686750
TI  - P. falciparum isolate-specific distinct patterns of induced apoptosis in
      pulmonary and brain endothelial cells.
AB  - The factors implicated in the transition from uncomplicated to severe clinical
      malaria such as pulmonary oedema and cerebral malaria remain unclear. It is known
      that alterations in vascular integrity due to endothelial cell (EC) activation
      and death occur during severe malaria. In this study, we assessed the ability of
      different P. falciparum clinical isolates to induce apoptosis in ECs derived from
      human lung and brain. We observed that induction of EC apoptosis was sensitive to
      the environmental pH and required direct contact between the parasite and the
      cell, though it was not correlated to the ability of the parasite to cytoadhere.
      Moreover, the extent of induced apoptosis in the two EC types varied with the
      isolate. Analysis of parasite genes transcript led us to propose that the
      activation of different pathways, such as Plasmodium apoptosis-linked
      pathogenicity factors (PALPF), PALPF-2, PALPF-5 and PF11_0521, could be implied
      in EC death. These observations provide an experimental framework to decipher the
      molecular mechanism implicated in the genesis of severe malaria. 

PMID- 24686752
TI  - Beyond picture naming: norms and patient data for a verb-generation task.
AB  - PURPOSE: In the current study, the authors aimed to (a) acquire a set of verb
      generation to picture norms; and (b) probe its utility as an outcomes measure in
      aphasia treatment. METHOD: In Phase I, the verb-generation normative sample, 50
      healthy volunteers generated verbs for 218 pictures of common objects
      (interstimulus interval = 5 s). In Phase II, 4 persons with aphasia (PWAs)
      generated verbs for 60 objects (interstimulus interval = 10 s). Their stimuli
      consisted of objects that were (a) recently trained (for object naming; n = 20),
      (b) untrained (a control set; n = 20), or (c) from a set of pictures named
      correctly at baseline (n = 20). Verb generation was acquired twice: once 2 months
      into and once following a 6-month home practice program. RESULTS: No objects
      elicited perfect verb agreement in the normed sample. Stimuli with the highest
      percent agreement were mostly artifacts and dominant verbs primary functional
      associates. Although not targeted in treatment or home practice, PWAs mostly
      improved performance in verb generation postpractice. CONCLUSIONS: A set of
      clinically and experimentally useful verb-generation norms was acquired for a
      subset of the Snodgrass and Vanderwart (1980) picture set. More cognitively
      demanding than confrontation naming, this task may help to fill the sizeable gap
      between object picture naming and propositional speech.

PMID- 24686753
TI  - Psychiatrist and patient responses to suspected medication nonadherence in
      schizophrenia spectrum disorders.
AB  - OBJECTIVE: Long-term results in schizophrenia treatment continue to be
      unsatisfactory, with many patients nonadherent to treatment and relapsing
      frequently. This study aimed to examine how perceived nonadherence leads
      psychiatrists to implement adherence-enhancing measures and to identify barriers
      and facilitators for the implementation of adherence-enhancing measures. METHODS:
      A cross-sectional survey was conducted with German hospital psychiatrists and
      their inpatients who had a diagnosis of schizophrenia or schizoaffective
      disorder. RESULTS: Interviews were conducted with 121 psychiatrists or resident
      psychiatrists and their 213 inpatients. Psychiatrists recognized nonadherence as
      an important factor for hospital admission only when directly asked about it.
      Psychiatrists implemented a plethora of adherence interventions that in many
      cases constituted only intensive talks and no structured interventions. Of four
      core interventions addressed in the survey-depot administration of medication,
      psychoeducation for patients, psychoeducation for relatives, and arrangement of
      first follow-up visit-the implementation rates were surprisingly high for depot
      prescription of antipsychotics (>30%) and psychoeducation for patients but
      dramatically low for arrangement of follow-up visits and psychoeducation for
      relatives. Patients with poor previous adherence (according to the physician's
      estimate) received more adherence measures. In addition, patients with
      involuntary admission were more likely to receive depot medications, and
      psychoeducation was more often implemented for younger patients and for patients
      at university hospitals. CONCLUSIONS: Treatment nonadherence is often
      underestimated by psychiatrists. Obstacles to the implementation of adherence
      enhancing interventions occur in routine daily care. Integrated-care programs
      addressing adherence issues, communication between inpatient and outpatient
      treatment, implementation of adherence measures, and better involvement of
      patients in clinical decisions may help to overcome these barriers.

PMID- 24686755
TI  - [Radiology reports - how do I inform my doctor?].

PMID- 24686754
TI  - Manufacturing of three-dimensionally microstructured nanocomposites through
      microfluidic infiltration.
AB  - Microstructured composite beams reinforced with complex three-dimensionally (3D)
      patterned nanocomposite microfilaments are fabricated via nanocomposite
      infiltration of 3D interconnected microfluidic networks. The manufacturing of the
      reinforced beams begins with the fabrication of microfluidic networks, which
      involves layer-by-layer deposition of fugitive ink filaments using a dispensing
      robot, filling the empty space between filaments using a low viscosity resin,
      curing the resin and finally removing the ink. Self-supported 3D structures with
      other geometries and many layers (e.g. a few hundreds layers) could be built
      using this method. The resulting tubular microfluidic networks are then
      infiltrated with thermosetting nanocomposite suspensions containing nanofillers
      (e.g. single-walled carbon nanotubes), and subsequently cured. The infiltration
      is done by applying a pressure gradient between two ends of the empty network
      (either by applying a vacuum or vacuum-assisted microinjection). Prior to the
      infiltration, the nanocomposite suspensions are prepared by dispersing
      nanofillers into polymer matrices using ultrasonication and three-roll mixing
      methods. The nanocomposites (i.e. materials infiltrated) are then solidified
      under UV exposure/heat cure, resulting in a 3D-reinforced composite structure.
      The technique presented here enables the design of functional nanocomposite
      macroscopic products for microengineering applications such as actuators and
      sensors.

PMID- 24686756
TI  - [Staphylococcus aureus bacteremia].

PMID- 24686758
TI  - [Coping with chronic disease].
AB  - Patients suffering form chronic diseases have to deal with several problems, the
      illness itself only being one of them. Health care providers have to undergo a
      paradigm shift to be able to meet the new challenges which differ from those in
      acute care. From the patient's perspective, coping with a chronic disease is not
      a limited process, but encompasses different, often recurring phases (trajectory
      model). The treating physician's support may comprise the offering of information
      on general and specific stress factors (physical, emotional, social), empathy,
      respecting the individual's expertise and activating a patient's resources and
      self-efficacy. The amount of support given is limited by the treating physician's
      expert knowledge in this area. Physicians should respect their own limits and
      involve specialists, supervision or Balint groups. 

PMID- 24686759
TI  - ["Crazy paving" of the lungs].
AB  - The term "crazy paving" describes an unspecific pattern in thoracic computed
      tomography mimicking a paving stone configuration. This pattern can be caused by
      a number of differential diagnosis, for example alveolar hemorrhage, alveolar
      proteinosis, lipoid pneumonia or adenocarcinoma in situ. The knowledge of the
      correlation between imaging findings, histopathological pattern and clinical
      presentation prepares the clinician to understand the pathophysiology and to
      initiate the right therapeutic processes. In the following review, we describe
      the most common diseases and their radiologic correlation in daily practice. 

PMID- 24686761
TI  - [Malignant hypoglycaemia].
AB  - We describe the case of a 19-years old patient with seizure due to severe
      hypoglycaemia during general practitioner consultation. Because of
      hyperinsulinaemic hypoglycaemia and suspected liver metastasis a neuroendocrine
      hormone active tumor was suspected. After liver biopsy and CT scan a
      neuroendocrine pancreatic tumor could be diagnosed. Afterwards oncological
      therapy was induced. 

PMID- 24686760
TI  - [Focal therapy-a new era in the treatment of prostate cancer].
AB  - Treatment options for prostate cancer are currently widely discussed in the media
      and by urologic associations. International studies showed that current treatment
      options may significantly affect the quality of life (including incontinence and
      erectile dysfunction) while only offering marginal survival benefits. Low to
      medium risk patients in particular don't seem to be ideal candidates for radical
      treatment by surgery of radio therapy. For this large group of patients focal
      therapy offers additional valuable treatment option. Malignant prostate tissue
      can be specifically ablated by High-Intensity Focused Ultrasound (HIFU). Thus,
      the cancer can be controlled without removing the whole prostate and with minimal
      side effects. Multimodal magnetic resonance tomography, specific biopsies and
      monitoring contribute to the safety of this new treatment strategy. 

PMID- 24686763
TI  - [Are compression stockings after deep venous thrombosis pointless?].

PMID- 24686764
TI  - ["Red Flags" for back pain are not as threatening as the name suggests].

PMID- 24686766
TI  - [CME rheumatology 2. Painless swelling of the finger joints].

PMID- 24686768
TI  - [Personalities in the history of medicine. Alois Alzheimer, Paul Langerhans].

PMID- 24686770
TI  - Polyaniline:poly(sodium 4-styrenesulfonate)-stabilized gold nanoparticles as
      efficient, versatile catalysts.
AB  - Gold nanoparticles were stabilized by a polyaniline:poly(sodium 4
      styrenesulfonate) (PANI:PSS) matrix and readily dispersed in water over a wide
      range of pH. In contrast to nanoparticles passivated by alkanethiolates that
      formed a compact capping layer on the nanoparticle surface, the PANI:PSS-Au
      nanocomposites exhibited apparent catalytic activity in the reduction of 4
      nitrophenol in the presence of excessive NaBH4, with reasonably good
      recyclability, which was likely due to the large accessible surface area. In
      addition, the PANI:PSS-Au nanocomposites also demonstrated peroxidase-like
      catalytic activity as evidenced by the colorimetric detection of H2O2 and glucose
      with PANI:PSS-Au as the enzymatic mimic. The present method may find potential
      applications in the design, preparation and functionalization of noble
      nanoparticles as efficient, versatile, and recyclable catalysts with high
      dispersibility and stability in aqueous media. 

PMID- 24686771
TI  - Radical O-O coupling reaction in diferrate-mediated water oxidation studied using
      multireference wave function theory.
AB  - The O-O (oxygen-oxygen) bond formation is widely recognized as a key step of the
      catalytic reaction of dioxygen evolution from water. Recently, the water
      oxidation catalyzed by potassium ferrate (K2FeO4) was investigated on the basis
      of experimental kinetic isotope effect analysis assisted by density functional
      calculations, revealing the intramolecular oxo-coupling mechanism within a di
      iron(vi) intermediate, or diferrate [Sarma et al., J. Am. Chem. Soc., 2012, 134,
      15371]. Here, we report a detailed examination of this diferrate-mediated O-O
      bond formation using scalable multireference electronic structure theory. High
      dimensional correlated many-electron wave functions beyond the one-electron
      picture were computed using the ab initio density matrix renormalization group
      (DMRG) method along the O-O bond formation pathway. The necessity of using large
      active space arises from the description of complex electronic interactions and
      varying redox states both associated with two-center antiferromagnetic
      multivalent iron-oxo coupling. Dynamic correlation effects on top of the active
      space DMRG wave functions were additively accounted for by complete active space
      second-order perturbation (CASPT2) and multireference configuration interaction
      (MRCI) based methods, which were recently introduced by our group. These
      multireference methods were capable of handling the double shell effects in the
      extended active space treatment. The calculations with an active space of 36
      electrons in 32 orbitals, which is far over conventional limitation, provide a
      quantitatively reliable prediction of potential energy profiles and confirmed the
      viability of the direct oxo coupling. The bonding nature of Fe-O and dual bonding
      character of O-O are discussed using natural orbitals. 

PMID- 24686772
TI  - Prostate cancer diagnosis through electronic nose in the urine headspace setting:
      a pilot study.
AB  - BACKGROUND: To evaluate the efficacy of prostate cancer (PCa) detection by the
      electronic nose (EN) on human urine samples. METHODS: Urine samples were obtained
      from candidates of prostate biopsy (PB). Exclusion criteria were a history of
      urothelial carcinoma or other malignant disease, urine infection, fasting for <12
      h before PB or ingestion of alcohol or foods that might alter the urine smell in
      the last 24 h. The initial part of the voided urine and the midstream were
      collected separately in two sterile containers. Both samples were analyzed by the
      EN immediately after the collection. All patients underwent a standard
      transperineal, transrectal-ultrasound-guided PB. The pathological results were
      compared with the outcomes of the EN. Sensitivity and specificity of EN were
      assessed. RESULTS: Forty-one men were included in the study. Fourteen out of the
      41 patients were positive for PCa. Midstream urine did not correlate
      significantly neither with a positive nor with a negative PB. Instead,
      significantly different results on the initial part of the urine stream between
      positive and negative PBs were obtained. The EN correctly recognized 10 out of
      the 14 cases (that is, sensitivity 71.4% (confidence interval (CI) 42-92%)) of
      PCa while four were false negatives. Moreover, the device recognized as negative
      25 out of the 27 (that is, specificity 92.6% (CI 76-99%)) samples of negative
      PBs, with only two false positives. CONCLUSIONS: We believe this is the first
      demonstration of an olfactory imprinting of the initial part of the urine stream
      in patients with PCa that was revealed by an EN, with high specificity.

PMID- 24686769
TI  - Bacillus thuringiensis subsp. israelensis and its dipteran-specific toxins.
AB  - Bacillus thuringiensis subsp. israelensis (Bti) is the first Bacillus
      thuringiensis to be found and used as an effective biological control agent
      against larvae of many mosquito and black fly species around the world. Its
      larvicidal activity resides in four major (of 134, 128, 72 and 27 kDa) and at
      least two minor (of 78 and 29 kDa) polypeptides encoded respectively by cry4Aa,
      cry4Ba, cry11Aa, cyt1Aa, cry10Aa and cyt2Ba, all mapped on the 128 kb plasmid
      known as pBtoxis. These six delta-endotoxins form a complex parasporal
      crystalline body with remarkably high, specific and different toxicities to
      Aedes, Culex and Anopheles larvae. Cry toxins are composed of three domains
      (perforating domain I and receptor binding II and III) and create cation
      selective channels, whereas Cyts are composed of one domain that acts as well as
      a detergent-like membrane perforator. Despite the low toxicities of Cyt1Aa and
      Cyt2Ba alone against exposed larvae, they are highly synergistic with the Cry
      toxins and hence their combinations prevent emergence of resistance in the
      targets. The lack of significant levels of resistance in field mosquito
      populations treated for decades with Bti-bioinsecticide suggests that this
      bacterium will be an effective biocontrol agent for years to come. 

PMID- 24686773
TI  - Intermittent androgen deprivation is a rational standard-of-care treatment for
      all stages of progressive prostate cancer: results from a systematic review and
      meta-analysis.
AB  - BACKGROUND: The optimal hormone treatment strategy in prostate cancer is
      uncertain, particularly in patients with metastatic disease. We aimed to compare
      the relative benefits and harms of intermittent androgen deprivation (IAD) to
      continuous androgen deprivation (CAD) in all stages of prostate cancer. METHODS:
      We included eight randomised control trials (4668 patients) in our systematic
      review and meta-analysis. Median follow-up ranged from 29 to 118 months. Pooled
      hazard ratios (HRs) were calculated for overall survival (OS), cancer-specific
      survival, time to cancer progression and mortality unrelated to prostate cancer.
      The relative effect of treatment in patients with metastatic and those with non
      metastatic disease was compared using pre-planned subgroup analysis. RESULTS:
      There was no difference in OS between patients treated with IAD and CAD (HR 1.01,
      95% confidence interval (CI) 0.93-1.10); nor was there any difference in cancer
      specific survival (HR 1.03; 95% CI 0.88-1.21). There was a non-significant trend
      towards longer time to prostate cancer progression for IAD (HR 0.93, 95% CI 0.84
      1.04), raising the possibility of slower selection for castrate resistance. There
      was no significant difference in OS when analysis was restricted to patients with
      metastatic disease (HR 1.04, 95% CI 0.91-1.19) or patients without metastatic
      disease (HR 1.06, 95% CI 0.91-1.23) (test for subgroup differences P=0.84). Most
      studies found an improvement in quality of life or toxicity profile with IAD.
      CONCLUSIONS: IAD is non-inferior to CAD in terms of OS and cancer-specific
      survival, and is at least non-inferior in terms of time to progression. This meta
      analysis confirms IAD as a valid standard of care for managing prostate cancer
      patients.

PMID- 24686774
TI  - Hospitalist workload: the search for the magic number.

PMID- 24686775
TI  - Additions to the Babbage bibliography.

PMID- 24686776
TI  - Test-retest stability of word retrieval in aphasic discourse.
AB  - PURPOSE: This study examined the test-retest stability of select word-retrieval
      measures in the discourses of people with aphasia who completed a 5-stimulus
      discourse task. METHOD: Discourse samples across 3 sessions from 12 individuals
      with aphasia were analyzed for the stability of measures of informativeness,
      efficiency, main concepts, noun and verb retrieval, word-finding difficulty, and
      lexical diversity. Values for correlation coefficients and the minimal detectable
      change score were used to assess stability for research and clinical decision
      making. RESULTS: Measures stable enough to use in group research studies included
      the number of words; the number of correct information units (CIUs); the number
      of accurate-complete, accurate-incomplete, and absent main concepts; the
      percentage of T-units that had word-finding behaviors of any kind; the percentage
      of T-units that contained empty words; and a lexical diversity measure. Words per
      minute, CIUs per minute, and the percentage of T-units that contained time
      fillers or delays were sufficiently stable to use when making clinical decisions
      about an individual. CONCLUSION: Although several of the measures demonstrated
      acceptable stability for group research studies, relatively few were sufficiently
      stable for making clinical decisions about individuals on the basis of a single
      administration.

PMID- 24686777
TI  - Vocal interaction between children with Down syndrome and their parents.
AB  - PURPOSE: The purpose of this study was to describe differences in parent input
      and child vocal behaviors of children with Down syndrome (DS) compared with
      typically developing (TD) children. The goals were to describe the language
      learning environments at distinctly different ages in early childhood. METHOD:
      Nine children with DS and 9 age-matched TD children participated; 4 children in
      each group were ages 9-11 months, and 5 were between 25 and 54 months. Measures
      were derived from automated vocal analysis. A digital language processor measured
      the richness of the child's language environment, including number of adult
      words, conversational turns, and child vocalizations. RESULTS: Analyses indicated
      no significant differences in words spoken by parents of younger versus older
      children with DS and significantly more words spoken by parents of TD children
      than parents of children with DS. Differences between the DS and TD groups were
      observed in rates of all vocal behaviors, with no differences noted between the
      younger versus older children with DS, and the younger TD children did not
      vocalize significantly more than the younger DS children. CONCLUSIONS: Parents of
      children with DS continue to provide consistent levels of input across the early
      language learning years; however, child vocal behaviors remain low after the age
      of 24 months, suggesting the need for additional and alternative intervention
      approaches.

PMID- 24686778
TI  - A longitudinal study in adults with sequential bilateral cochlear implants: time
      course for individual ear and bilateral performance.
AB  - PURPOSE: The purpose of this study was to examine the rate of progress in the 2nd
      implanted ear as it relates to the 1st implanted ear and to bilateral performance
      in adult sequential cochlear implant recipients. In addition, this study aimed to
      identify factors that contribute to patient outcomes. METHOD: The authors
      performed a prospective longitudinal study in 21 adults who received bilateral
      sequential cochlear implants. Testing occurred at 6 intervals: prebilateral
      through 12 months postbilateral implantation. Measures evaluated speech
      recognition in quiet and noise, localization, and perceived benefit. RESULTS:
      Second ear performance was similar to 1st ear performance by 6 months
      postbilateral implantation. Bilateral performance was generally superior to
      either ear alone; however, participants with shorter 2nd ear length of deafness
      (<20 years) had more rapid early improvement and better overall outcomes than
      those with longer 2nd ear length of deafness (>30 years). All participants
      reported bilateral benefit. CONCLUSIONS: Adult cochlear implant recipients
      demonstrated benefit from 2nd ear implantation for speech recognition,
      localization, and perceived communication function. Because performance outcomes
      were related to length of deafness, shorter time between surgeries may be
      warranted to reduce negative length-of-deafness effects. Future study may clarify
      the impact of other variables, such as preimplant hearing aid use, particularly
      for individuals with longer periods of deafness.

PMID- 24686779
TI  - Three-dimensional histologic validation of high-resolution SPECT of antibody
      distributions within xenografts.
AB  - Longitudinal imaging of intratumoral distributions of antibodies in vivo in mouse
      cancer models is of great importance for developing cancer therapies. In this
      study, multipinhole SPECT with sub-half-millimeter resolution was tested for
      exploring intratumoral distributions of radiolabeled antibodies directed toward
      the epidermal growth factor receptor (EGFr) and compared with full 3-dimensional
      target expression assessed by immunohistochemistry. METHODS: (111)In-labeled
      zalutumumab, a human monoclonal human EGFr-targeting antibody, was administered
      at a nonsaturating dose to 3 mice with xenografted A431 tumors exhibiting high
      EGFr expression. Total-body and focused in vivo tumor SPECT was performed at 0
      and 48 h after injection and compared both visually and quantitatively with full
      3-dimensional immunohistochemical staining for EGFr target expression. RESULTS:
      SPECT at 48 h after injection showed that activity was predominantly concentrated
      in the tumor (10.5% +/- 1.3% of the total-body activity; average concentration,
      30.1% +/- 4.6% of the injected dose per cubic centimeter). (111)In-labeled EGFr
      targeting antibodies were distributed heterogeneously throughout the tumor. Some
      hot spots were observed near the tumor rim. Immunohistochemistry indicated that
      the antibody distributions obtained by SPECT were morphologically similar to
      those obtained for ex vivo EGFr target expression. Regions showing low SPECT
      activity were necrotic or virtually negative for EGFr target expression. A good
      correlation (r = 0.86, P < 0.0001) was found between the percentage of regions
      showing low activity on SPECT and the percentage of necrotic tissue on
      immunohistochemistry. CONCLUSION: Multipinhole SPECT enables high-resolution
      visualization and quantification of the heterogeneity of (111)In-zalutumumab
      concentrations in vivo.

PMID- 24686780
TI  - Molecular imaging with macrophage CRIg-targeting nanobodies for early and
      preclinical diagnosis in a mouse model of rheumatoid arthritis.
AB  - An accurate and noninvasive tracer able to detect molecular events underlying the
      development of rheumatoid arthritis (RA) would be useful for RA diagnosis and
      drug efficacy assessment. A complement receptor of the Ig superfamily (CRIg) is
      expressed on synovial macrophages of RA patients, making it an interesting target
      for molecular imaging of RA. We aim to develop a radiotracer for the
      visualization of CRIg in a mouse model for RA using radiolabeled single-domain
      variable antibody VHH fragments (Nanobodies). METHODS: Quantitative polymerase
      chain reaction was used to locate CRIg expression in mice with collagen-induced
      arthritis (CIA). A Nanobody, NbV4m119, was generated to specifically target CRIg.
      Flow cytometry, phosphorimaging, and confocal microscopy were used to confirm
      NbVm119 binding to CRIg-positive cells. SPECT (SPECT/CT) was used to image
      arthritic lesions in the inflamed paws of 29 mice using (99m)Tc-NbV4m119
      Nanobody. RESULTS: CRIg is constitutively expressed in the liver and was found to
      be upregulated in synovial tissues of CIA mice. SPECT/CT imaging revealed that
      (99m)Tc-NbV4m119 specifically targeted CRIg-positive liver macrophages in naive
      wild-type but not in CRIg(-/-) (CRIg knockout) mice. In CIA mice, (99m)Tc
      NbV4m119 accumulation in arthritic lesions increased according to the severity of
      the inflammation. In the knees of mice with CIA, (99m)Tc-NbV4m119 was found to
      accumulate even before the onset of macroscopic clinical symptoms. CONCLUSION:
      SPECT/CT imaging with (99m)Tc-NbV4m119 visualizes joint inflammation in CIA.
      Furthermore, imaging could predict which mice will develop clinical symptoms
      during CIA. Consequently, imaging of joint inflammation with CRIg-specific
      Nanobodies offers perspectives for clinical applications in RA patients.

PMID- 24686781
TI  - Laparoscopic sentinel lymph node versus hyperextensive pelvic dissection for
      staging clinically localized prostate carcinoma: a prospective study of 200
      patients.
AB  - Lymph node metastasis is an important prognostic factor in prostate cancer (PC).
      The aim of this prospective study was to validate, through laparoscopic surgery,
      the accuracy of the isotopic sentinel lymph node (SLN) technique correlated with
      hyperextensive pelvic resection (extended pelvic lymphadenectomy dissection) in
      patients with localized PC, candidates for local curative treatment. METHODS: A
      transrectal ultrasound-guided injection of (99m)Tc-sulfur rhenium colloid (0.3
      mL/100 MBq) in each prostatic lobe was performed the day before surgery.
      Detection was performed intraoperatively with a laparoscopic probe, followed by
      extensive resection. SLN counts were performed in vivo and confirmed ex vivo.
      Histologic analysis was performed by hematoxylin-phloxine-safran staining,
      followed by immunohistochemistry if the SLN was free of metastasis. RESULTS: Two
      hundred three patients with PC at intermediate or high risk of lymph node
      metastases were included. The intraoperative detection rate was 96% (195/203).
      Thirty-five patients had lymph node metastases, 19 only in the SLN. The false
      negative rate was 8.5% (3/35). Unilateral surgical SLN detection did not validate
      bilateral pelvic lymph node status, and extended pelvic lymphadenectomy
      dissection was necessary on the opposite side of detection to minimize the false
      negative rate (2.8% [1/35]). A significant metastatic sentinel invasion in the
      common iliac region existed (9.3%) but was always associated with other
      metastatic node areas. The internal iliac region was the primary metastatic site
      (40.7%). Finally, this series invalidated any justification for a standard or
      limited dissection, which would have missed 51.9% and 74.1% of lymph node
      metastases, respectively. CONCLUSION: The radioisotope SLN identification method
      up to the common iliac region is successful to identify sentinel nodes during
      laparoscopic surgery per hemipelvis to be acceptably considered as an isolated
      procedure and should be validated for intermediate- and high-risk patients.

PMID- 24686782
TI  - In vivo evaluation of 18F-MNI698: an 18F-labeled radiotracer for imaging of
      serotonin 4 receptors in brain.
AB  - Serotonin 4 receptors (5-hydroxytryptamine receptor 4 [5HT4R]) hold promise as a
      novel therapeutic approach to multiple brain disorders, including Alzheimer and
      Huntington disease. In vivo imaging of these receptors with selective 5HT4R
      radiotracers and PET would be valuable to investigate alterations in 5HT4R in
      different brain disorders and to assist drug discovery. In this study, (18)F
      MNI698 was evaluated as a potential PET radiotracer for imaging of 5HT4R in the
      brain. METHODS: Eighteen PET studies were performed in 3 adult rhesus monkeys.
      The radiotracer was administered as a bolus intravenous injection or bolus plus
      constant infusion (time that would be required to inject the bolus at the
      infusion rate = 60 min), and arterial blood was collected for data
      quantification. Kinetic models were used to estimate distribution volumes and
      binding potentials, for which the cerebellum was used as a reference region.
      (18)F-MNI698 test-retest variability and upper mass dose limits were determined.
      Preblocking studies using several doses of SB204070, a selective 5HT4R
      antagonist, were performed. RESULTS: (18)F-MNI698 avidly entered the monkey brain
      (peak percentage injected dose of ~ 6.6%), and its brain distribution was
      consistent with known 5HT4R densities. At 120 min after bolus injection and after
      the start of radiotracer infusion, only less than 5% and approximately 10% parent
      compound was present in blood, respectively. Measured binding potentials were
      underestimated by 22%-36% when noninvasive methods were used for data
      quantification in comparison with invasive methods. A good agreement was found
      between test-retest measurements. The radiotracer upper mass dose limit (<5%
      occupancy) was determined to be 13.1 MUg per 70 kg of body weight. SB204070
      blocked the radiotracer binding in a dose-dependent manner. CONCLUSION: Data
      indicate that (18)F-MNI698 is a promising PET radiotracer for imaging of 5HT4R in
      the brain, and human studies are warranted based on these study results.

PMID- 24686784
TI  - Contributions and challenges for network models in cognitive neuroscience.
AB  - The confluence of new approaches in recording patterns of brain connectivity and
      quantitative analytic tools from network science has opened new avenues toward
      understanding the organization and function of brain networks. Descriptive
      network models of brain structural and functional connectivity have made several
      important contributions; for example, in the mapping of putative network hubs and
      network communities. Building on the importance of anatomical and functional
      interactions, network models have provided insight into the basic structures and
      mechanisms that enable integrative neural processes. Network models have also
      been instrumental in understanding the role of structural brain networks in
      generating spatially and temporally organized brain activity. Despite these
      contributions, network models are subject to limitations in methodology and
      interpretation, and they face many challenges as brain connectivity data sets
      continue to increase in detail and complexity. 

PMID- 24686783
TI  - Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.
AB  - MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease
      protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal
      dementia. Using exome sequencing, we identified mutations in MATR3 in ALS
      kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and
      without MATR3 mutations. Our data provide more evidence supporting the role of
      aberrant RNA processing in motor neuron degeneration. 

PMID- 24686785
TI  - Serial dependence in visual perception.
AB  - Visual input often arrives in a noisy and discontinuous stream, owing to head and
      eye movements, occlusion, lighting changes, and many other factors. Yet the
      physical world is generally stable; objects and physical characteristics rarely
      change spontaneously. How then does the human visual system capitalize on
      continuity in the physical environment over time? We found that visual perception
      in humans is serially dependent, using both prior and present input to inform
      perception at the present moment. Using an orientation judgment task, we found
      that, even when visual input changed randomly over time, perceived orientation
      was strongly and systematically biased toward recently seen stimuli. Furthermore,
      the strength of this bias was modulated by attention and tuned to the spatial and
      temporal proximity of successive stimuli. These results reveal a serial
      dependence in perception characterized by a spatiotemporally tuned, orientation
      selective operator-which we call a continuity field-that may promote visual
      stability over time. 

PMID- 24686786
TI  - Attentive scanning behavior drives one-trial potentiation of hippocampal place
      fields.
AB  - The hippocampus is thought to have a critical role in episodic memory by
      incorporating the sensory input of an experience onto a spatial framework
      embodied by place cells. Although the formation and stability of place fields
      requires exploration, the interaction between discrete exploratory behaviors and
      the specific, immediate and persistent modifications of neural representations
      required by episodic memory has not been established. We recorded place cells in
      rats and found that increased neural activity during exploratory head-scanning
      behaviors predicted the formation and potentiation of place fields on the next
      pass through that location, regardless of environmental familiarity and across
      multiple testing days. These results strongly suggest that, during the attentive
      behaviors that punctuate exploration, place cell activity mediates the one-trial
      encoding of ongoing experiences necessary for episodic memory. 

PMID- 24686788
TI  - Assessing the development of murine plasmacytoid dendritic cells in Peyer's
      patches using adoptive transfer of hematopoietic progenitors.
AB  - This protocol details a method to analyze the ability of purified hematopoietic
      progenitors to generate plasmacytoid dendritic cells (pDC) in intestinal Peyer's
      patch (PP). Common dendritic cell progenitors (CDPs, lin(-) c-kit(lo) CD115(+)
      Flt3(+)) were purified from the bone marrow of C57BL6 mice by FACS and
      transferred to recipient mice that lack a significant pDC population in PP; in
      this case, Ifnar(-/-) mice were used as the transfer recipients. In some mice,
      overexpression of the dendritic cell growth factor Flt3 ligand (Flt3L) was
      enforced prior to adoptive transfer of CDPs, using hydrodynamic gene transfer
      (HGT) of Flt3L-encoding plasmid. Flt3L overexpression expands DC populations
      originating from transferred (or endogenous) hematopoietic progenitors. At 7-10
      days after progenitor transfer, pDCs that arise from the adoptively transferred
      progenitors were distinguished from recipient cells on the basis of CD45 marker
      expression, with pDCs from transferred CDPs being CD45.1(+) and recipients being
      CD45.2(+). The ability of transferred CDPs to contribute to the pDC population in
      PP and to respond to Flt3L was evaluated by flow cytometry of PP single cell
      suspensions from recipient mice. This method may be used to test whether other
      progenitor populations are capable of generating PP pDCs. In addition, this
      approach could be used to examine the role of factors that are predicted to
      affect pDC development in PP, by transferring progenitor subsets with an
      appropriate knockdown, knockout or overexpression of the putative developmental
      factor and/or by manipulating circulating cytokines via HGT. This method may also
      allow analysis of how PP pDCs affect the frequency or function of other immune
      subsets in PPs. A unique feature of this method is the use of Ifnar(-/-) mice,
      which show severely depleted PP pDCs relative to wild type animals, thus allowing
      reconstitution of PP pDCs in the absence of confounding effects from lethal
      irradiation. 

PMID- 24686787
TI  - Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in
      Huntington's disease model mice.
AB  - Huntington's disease (HD) is characterized by striatal medium spiny neuron (MSN)
      dysfunction, but the underlying mechanisms remain unclear. We explored roles for
      astrocytes, in which mutant huntingtin is expressed in HD patients and mouse
      models. We found that symptom onset in R6/2 and Q175 HD mouse models was not
      associated with classical astrogliosis, but was associated with decreased Kir4.1
      K(+) channel functional expression, leading to elevated in vivo striatal
      extracellular K(+), which increased MSN excitability in vitro. Viral delivery of
      Kir4.1 channels to striatal astrocytes restored Kir4.1 function, normalized
      extracellular K(+), ameliorated aspects of MSN dysfunction, prolonged survival
      and attenuated some motor phenotypes in R6/2 mice. These findings indicate that
      components of altered MSN excitability in HD may be caused by heretofore unknown
      disturbances of astrocyte-mediated K(+) homeostasis, revealing astrocytes and
      Kir4.1 channels as therapeutic targets. 

PMID- 24686789
TI  - Helicobacter pylori, anemia, iron deficiency and thrombocytopenia among pregnant
      women at Khartoum, Sudan.
AB  - BACKGROUND: Helicobacter pylori is a common gut pathogen that is linked to many
      complications of pregnancy such as iron deficiency anemia, pre-eclampsia and
      thrombocytopenia. There are no published data on H. pylori in Sudan. METHODS: A
      cross-sectional study was conducted during the period May-June 2012 at the
      antenatal care unit of Khartoum Hospital, Sudan, to investigate prevalence of H.
      pylori and its association, if any, with anemia and thrombocytopenia. Obstetric
      and medical histories were gathered using questionnaires. Hemoglobin and serum
      ferritin were measured and H. pylori antibodies (IgA and IgG) investigated using
      ELISA. RESULTS: Among 179 women, rates of positivity for specific IgG formed
      against H. pylori were 69.8% (125/179), 94.0% (168/179) and 5.6% (10/179) for
      IgA, IgG and both IgG and IgA, respectively. There was no association between the
      expected risk factors (age, parity, education) and H. pylori seropositivity. Of
      these women, 42/179 (24.3%), 50/179 (28.9%) and 19/179 (11%), respectively, were
      anemic (hemoglobin <11 g/dl) or had iron deficiency (serum ferritin <15 ug/l) or
      iron deficiency anemia. There was no association between H. pylori infection and
      anemia (OR=1.0, 95% CI=0.3-3.2, p=1.0), iron deficiency (OR=0.6, 95% CI=0.1-3.8,
      p=0.367) or thrombocytopenia (OR=2.0, 95% CI=0.4-8.4, p=0.322). CONCLUSION: There
      is a high prevalence of H. pylori infection among pregnant women in Khartoum,
      Sudan, and it is not associated with anemia or thrombocytopenia.

PMID- 24686790
TI  - Hairpin DNA probes based on target-induced in situ generation of luminescent
      silver nanoclusters.
AB  - Novel hairpin DNA probes are designed and constructed based on target-induced in
      situ generation of luminescent silver nanoclusters. This design allows specific
      and versatile detection of diverse targets with easy operation and low cost. 

PMID- 24686791
TI  - Reduced nutrient pollution in a rural stream following septic tank upgrade and
      installation of runoff retention measures.
AB  - Surface water quality in the UK and much of Western Europe has improved in recent
      decades, in response to better point source controls and the regulation of
      fertilizer, manure and slurry use. However, diffuse sources of pollution, such as
      leaching or runoff of nutrients from agricultural fields, and micro-point sources
      including farmyards, manure heaps and septic tank sewerage systems, particularly
      systems without soil adsorption beds, are now hypothesised to contribute a
      significant proportion of the nutrients delivered to surface watercourses.
      Tackling such sources in an integrated manner is vital, if improvements in
      freshwater quality are to continue. In this research, we consider the combined
      effect of constructing small field wetlands and improving a septic tank system on
      stream water quality within an agricultural catchment in Cumbria, UK. Water
      quality in the ditch-wetland system was monitored by manual sampling at
      fortnightly intervals (April-October 2011 and February-October 2012), with the
      septic tank improvement taking place in February 2012. Reductions in nutrient
      concentrations were observed through the catchment, by up to 60% when considering
      total phosphorus (TP) entering and leaving a wetland with a long residence time.
      Average fluxes of TP, soluble reactive phosphorus (SRP) and ammonium-N (NH4-N) at
      the head of the ditch system in 2011 (before septic tank improvement) compared to
      2012 (after septic tank improvement) were reduced by 28%, 9% and 37%
      respectively. However, TP concentration data continue to show a clear dilution
      with increasing flow, indicating that the system remained point source dominated
      even after the septic tank improvement. 

PMID- 24686792
TI  - Can children with SLI detect cognitive conflict? Behavioral and
      electrophysiological evidence.
AB  - PURPOSE: This study examined whether children with specific language impairment
      (SLI) are deficient in detecting cognitive conflict between competing response
      tendencies in a GO/No-GO task. METHOD: Twelve children with SLI (ages 10-12), 22
      children with typical language development matched group-wise on age (TLD-A), and
      16 younger children with TLD (ages 8-9) matched group-wise on language skills
      (TLD-L) were tested using a behavioral GO/No-GO paradigm with simultaneous
      collection of event-related potentials. The N2 component was used as a neural
      index of the ability to detect conflict between GO and No-GO response tendencies.
      RESULTS: Hit rates did not differentiate the 3 groups. The TLD-L children
      demonstrated the highest false-alarm rates. The N2 component was attenuated and
      showed delayed divergence of GO and No-GO amplitudes in SLI relative to TLD-A
      children in response to stimuli presented at various probability levels. The N2
      effect in children with SLI resembled that of children with TLD who were
      approximately 3 years younger. CONCLUSIONS: School-age children with SLI exhibit
      a maturational lag in detecting conflict between competing response alternatives.
      Deficient conflict detection may in turn hinder these children's ability to
      resolve conflict among semantic representations that are activated during
      language processing.

PMID- 24686793
TI  - Intelligibility of American English vowels and consonants spoken by international
      students in the United States.
AB  - PURPOSE The purpose of this study was to examine the intelligibility of English
      consonants and vowels produced by Chinese-native (CN), and Korean-native (KN)
      students enrolled in American universities. METHOD 16 English-native (EN), 32 CN,
      and 32 KN speakers participated in this study. The intelligibility of 16 American
      English consonants and 16 vowels spoken by native and nonnative speakers of
      English was evaluated by EN listeners. All nonnative speakers also completed a
      survey of their language backgrounds. RESULTS Although the intelligibility of
      consonants and diphthongs for nonnative speakers was comparable to that of native
      speakers, the intelligibility of monophthongs was significantly lower for CN and
      KN speakers than for EN speakers. Sociolinguistic factors such as the age of
      arrival in the United States and daily use of English, as well as a linguistic
      factor, difference in vowel space between native (L1) and nonnative (L2)
      language, partially contributed to vowel intelligibility for CN and KN groups.
      There was no significant correlation between the length of U.S. residency and
      phoneme intelligibility. CONCLUSION Results indicated that the major difficulty
      in phonemic production in English for Chinese and Korean speakers is with vowels
      rather than consonants. This might be useful for developing training methods to
      improve English intelligibility for foreign students in the United States. 

PMID- 24686794
TI  - Sclerosing stromal tumour of the ovary presenting as precocious puberty: a rare
      neoplasm.
AB  - A 7-year-old Indian girl presented with symptoms of excessive development of
      breasts, early menarche, growth of pubic hairs, accelerated growth and abdominal
      distension. On clinical examination, a large right abdominopelvic mass was
      palpable. MRI revealed a large, heterogeneous, solid and cystic tumour in the
      right adnexal region, suggestive of an ovarian neoplasm. The hormonal profile
      showed markedly elevated oestradiol and low follicle-stimulating hormone levels.
      Clinical diagnosis of precocious puberty with right ovarian mass was concluded.
      Right-sided salpingo-oophorectomy was performed. Histopathology showed features
      consistent with sclerosing stromal tumour of the ovary. Postoperatively, signs
      and symptoms of precocity gradually regressed and her serum oestradiol level came
      down to normal. This is the first reported case from India. 

PMID- 24686795
TI  - Pulmonary alveolar microlithiasis: report of two brothers with the same illness
      and review of literature.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterised by
      extensive deposition of calpospherites within the alveoli. The disease is caused
      by mutations in the gene SLC34A2 encoding sodium-dependent phosphate co
      transporter. It is an autosomal recessive disease with sporadic cases worldwide.
      Most patients are asymptomatic at the time of diagnosis. It may progress slowly
      over years to respiratory failure and cor pulmonale. 

PMID- 24686796
TI  - Chest pain in a young patient: an unusual complication of Epstein-Barr virus.
AB  - A 29-year-old man presented with sudden left-sided pleuritic chest pain on a
      background of sore throat during the preceding week. On examination he had tender
      cervical lymphadenopathy, he was tachycardic and had a 24 mm Hg blood pressure
      difference between the left and right arms. Bloods revealed deranged liver
      function tests and a lymphocytosis. His D-dimer was raised, hence he was treated
      for presumed pulmonary embolism before imaging was available. Monospot test was
      positive. He subsequently had both a CT pulmonary angiogram and a CT angiogram of
      the aorta to exclude pulmonary embolism and aortic dissection. The CT revealed
      splenomegaly with a large subdiaphragmatic haematoma secondary to splenic
      rupture. This had likely caused referred pain through diaphragmatic irritation.
      He was taken to theatre for urgent splenectomy. The unifying diagnosis was
      infectious mononucleosis complicated by spontaneous splenic rupture secondary to
      Epstein-Barr virus infection. 

PMID- 24686797
TI  - Valvular aortic stenosis causing angiodysplasia and acquired von Willebrand's
      disease: Heyde's syndrome.

PMID- 24686798
TI  - Chest pain with raised troponin, ECG changes but normal coronary arteries.
AB  - A 65-year-old woman presented to A&E department, with acute onset central chest
      pain and dyspnoea. ECG showed dynamic T wave changes while 12 h troponin was
      elevated. A diagnosis of acute coronary syndrome was made and she underwent an
      inpatient coronary angiogram. Although her coronary arteries were normal,
      symptoms persisted and D-dimers were found to be elevated. This led to a CT
      pulmonary angiogram, which ruled out pulmonary embolism, but uncovered a large
      ascending aortic aneurysm with a contained leak. She was immediately transferred
      to regional cardiothoracic unit for urgent surgical intervention. This case
      report illustrates the importance of a good clinical history, physical
      examination and timely investigations. It also emphasises that not all chest pain
      events with elevated troponin level are due to acute coronary syndrome and that
      alternative diagnoses should still be considered. 

PMID- 24686799
TI  - Classical complication of infective endocarditis: ruptured, large mycotic
      cerebral aneurysm.

PMID- 24686800
TI  - Severe facial swelling in a pregnant woman after using hair dye.
AB  - A 33-year-old Caucasian pregnant woman (26 weeks' gestation) presented to the
      emergency department. She had a 2-day history of severe itching of the scalp and
      steadily worsening swelling of the face over the previous 12 h, which had
      extended to the neck. She had no difficulty breathing. The itching and swelling
      had developed 3 days after she had used hair dye. The patient had no history of
      allergic responses to hair dye or black henna tattoos. A diagnosis of type IV
      delayed hypersensitivity reaction was made. Permanent hair dyes are the most
      frequently used professional hair dyes and are most commonly based on
      paraphenylenediamine (PPD) or related chemicals. PPD is known to be one of the
      most potent allergens which cause allergic contact dermatitis. After treatment
      with intravenous antihistamines and steroids, the facial swelling reduced and the
      patient had completely recovered by the following day. 

PMID- 24686801
TI  - Pseudohyponatraemia due to L-asparaginase-associated dyslipidaemia in T-cell
      lymphoblastic lymphoma.

PMID- 24686802
TI  - Severe systemic candidiasis following immunomodulation therapy in in vitro
      fertilisation-embryo transfer (IVF-ET).
AB  - A 41-year-old nulliparous woman, with a medical history of unexplained
      infertility and multiple in vitro fertilisation (IVF) cycles with
      immunosuppressive therapy, was admitted to our tertiary obstetrics unit with
      sepsis at 18 weeks of pregnancy with dichorionic diamniotic twins. Candida
      glabrata was grown from her blood cultures, then subsequently from the liquor and
      placentae. She was treated with intravenous ambisome (amphotericin), but
      unfortunately, the infection resulted in the rupture of her membranes, preterm
      labour and the demise of her twins. She delivered both twins at 23 weeks, 3 days
      apart. The antifungal agent was changed to high-dose fluconazole after delivery
      for 2 weeks and she is now well. Women undergoing IVF-embryo transfer with
      immunomodulation therapy have a potential risk of developing candidal
      chorioamnionitis and sepsis. 

PMID- 24686803
TI  - Scapular winging in a patient with Arnold-Chiari malformation type 1 and
      syringomyelia.

PMID- 24686804
TI  - Empyema thoracis from an inhaled peanut.
AB  - A 77-year-old man with a history of pulmonary sarcoidosis was referred with
      persistent cough and reduced air entry on auscultation of the right lung base. He
      was an ex-smoker with a 40-pack-year history and his general practitioner was
      concerned about the possibility of bronchogenic carcinoma. A chest radiograph
      showed a right-sided pleural effusion with right mid-zone airspace opacification.
      Bronchoscopy revealed a peanut covered in mucus lodged in the right lower lobe
      bronchus. CT of the thorax demonstrated a multiloculated right pleural effusion
      with associated compressive atelectasis, consistent with chronic empyema. A chest
      drain was inserted but failed to fully clear the collection and the patient
      proceeded to a thoracoscopic decortication of a pleural empyema secondary to the
      right lower lobe obstruction from an inhaled peanut. His postoperative recovery
      was uncomplicated. 

PMID- 24686805
TI  - Methylmalonic acidaemia in pregnancy.
AB  - A 27-year-old woman with vitamin B12 responsive form of methylmalonic acidaemia
      (MMA) was pregnant with her first child. Treatment was unaltered during
      pregnancy: a low-protein diet and supplements. Her pregnancy was uncomplicated.
      She had a spontaneous delivery of a healthy girl with no MMA. The postpartum
      period was uneventful. MMA is a rare autosomal recessive metabolic disorder
      caused by a deficiency of methylmalonyl coenzyme A mutase or its vitamin B12
      dependent cofactor, leading to a toxic accumulation of methylmalonyl acid in
      plasma and urine. Clinical presentation involves otherwise unexplained
      deterioration and neurological dysfunction, recurrent vomiting, dehydration,
      lethargy, respiratory distress and muscular hypotonia. Long-term sequelae are
      neurological problems, renal failure, pancreatitis and cardiomyopathy. This is
      the 11th reported case of pregnancy in a woman with MMA. 

PMID- 24686806
TI  - Typhoid fever with caecal ulcer bleed: managed conservatively.
AB  - Typhoid fever is caused by enteroinvasive Gram-negative organism Salmonella
      typhi. The well-known complications of typhoid fever are intestinal haemorrhage
      and perforation. In the pre-antibiotic era, these complications were quite
      common, but in the current antibiotic era the incidence of these complications is
      on the decline. We report a case of a patient with typhoid fever who developed
      haematochezia during the hospital stay and was found to have caecal ulcer with an
      adherent clot on colonoscopy. He was managed successfully with conservative
      measures without endotherapy and there was no rebleed. 

PMID- 24686807
TI  - Chediak-Higashi syndrome in accelerated phase masquerading as severe acute
      malnutrition.
AB  - A toddler presented with poor appetite, weight loss and frequent respiratory
      tract infections for the past 6 months, fever and increasing paleness for the
      past 2 months and bilateral pedal oedema for the past 1 month. Anthropometry
      confirmed severe acute malnutrition. Clinical and laboratory evaluation revealed
      that the child also had hypopigmented hair and skin, splenohepatomegaly,
      pancytopenia and hypoalbuminaemia. The coexistence of hypopigmentation and
      suspected low immunity prompted us to investigate the child's hair, peripheral
      blood smear and bone marrow. Hair under light microscopy showed evenly
      distributed, large melanin granules, suggestive of Chediak-Higashi syndrome
      (CHS). Peripheral blood smear and bone marrow aspirate examinations revealed
      abnormal large intracytoplasmic granules, which was diagnostic of CHS. The
      child's investigations revealed coexistent hemophagocytic lymphohistiocytosis,
      confirming the diagnosis of CHS in 'accelerated phase', which is fatal if not
      treated. The parents prematurely took the child home against medical advice,
      before definitive therapy could be instituted. 

PMID- 24686808
TI  - Transstyloid, transscaphoid, transcapitate fracture: a variant of scaphocapitate
      fractures.
AB  - Transstyloid, transscaphoid, transcapitate fractures are uncommon. We report the
      case of a 28-year-old man who sustained this fracture following direct trauma.
      The patient was successfully treated by open reduction internal fixation of the
      scaphoid and proximal capitate fragment, with a good clinical outcome at 1-year
      follow-up. This pattern is a new variant of scaphocapitate fracture as involves a
      fracture of the radial styloid as well. 

PMID- 24686809
TI  - Does minimally invasive also stand for minimal patient risk? Lessons from an
      upper gastrointestinal endoscopy.

PMID- 24686810
TI  - Peroneal nerve involvement as initial manifestation of primary systemic
      vasculitis.
AB  - We report a case of two patients with foot drop due to peroneal nerve infarct as
      early sign of two different forms of primary systemic vasculitides: a
      predominantly small-vessel p-antineutrophil cytoplasmic antibody-positive
      vasculitis (microscopic polyangiitis) and a predominantly medium-vessel
      vasculitis (polyarteritis nodosa). 

PMID- 24686811
TI  - Incidental 'ethmoid sinolith'--an unusual cause of frontal recess obstruction.
AB  - We report a case of a middle aged, hypertensive man who presented with nasal
      obstruction, sneezing spells, headache and nasal discharge of long duration. On
      evaluation, he was diagnosed to have a deviated nasal septum with allergic
      rhinosinusitis with sinonasal polyposis. CT of the paranasal sinuses revealed a
      hyperdense, oval structure suggestive of a sinolith in the right anterior ethmoid
      sinus. The patient underwent septoplasty with right Draf 2B procedure and
      extraction of the sinolith from the ethmoid sinus. 

PMID- 24686812
TI  - Couvelaire uterus.

PMID- 24686813
TI  - Knockdown of the HDAC1 promotes the directed differentiation of bone mesenchymal
      stem cells into cardiomyocytes.
AB  - Failure of the directed differentiation of the transplanted stem cells into
      cardiomyocytes is still a major challenge of cardiac regeneration therapy. Our
      recent study has demonstrated that the expression of histone deacetylase 1
      (HDAC1) is decreased in bone mesenchymal stem cells (BMSCs) during their
      differentiation into cardiomyocytes. However, the potential roles of HDAC1 in
      cardiac cell differentiation of BMSCs, as well as the mechanisms involved are
      still unclear. In current study, the expression of HDAC1 in cultured rat BMSCs is
      knocked down by lentiviral vectors expressing HDAC1-RNAi. The directed
      differentiation of BMSCs into cardiomyocytes is evaluated by the expression
      levels of cardiomyocyte-related genes such as GATA-binding protein 4 (GATA-4),
      Nirenberg, Kim gene 2 homeobox 5 (Nkx2.5), cardiac troponin T (CTnT), myosin
      heavy chain (MHC), and connexin-43. Compared with that in control BMSCs, the
      expression of these cardiomyocyte-related genes is significantly increased in
      these HDAC1 deficient stem cells. The results suggest that HDAC1 is involved in
      the cardiomyocyte differentiation of BMSCs. Knockdown of the HDAC1 may promote
      the directed differentiation of BMSCs into cardiomyocytes. 

PMID- 24686814
TI  - UV light induced plasticization and light activated shape memory of spiropyran
      doped ethylene-vinyl acetate copolymers.
AB  - Light activated shape memory polymers (LASMPs) are relatively new kinds of smart
      materials and have significant technological applications ranging from biomedical
      devices to aerospace technology. EVA films doped with spiropyran with contents
      ranging from 0.1% to 3% show efficient UV activated shape memory behaviors if the
      fixed shape deformation is limited within 80%. For EVA films containing 3%
      spiropyran, UV irradiation causes a decrease in EVA modulus of about 44%. FT-IR
      and solid (13)C NMR in association with UV-vis absorption analysis demonstrate
      that UV irradiation transforms spiropyran from the SP form to the MC form,
      meanwhile, it induces an increase in the molecular mobility in the amorphous
      phase of EVA. Thus, the spiropyran-doped EVA films act as LASMPs via a mechanism
      of light induced plasticization. Light activated spiropyran acts as a plasticizer
      to EVA. 

PMID- 24686815
TI  - [Equine research science meeting in Switzerland].

PMID- 24686816
TI  - [Stress parameters and behaviour of horses in walkers with and without the use of
      electricity].
AB  - In order to investigate stress responses of horses in walkers with and without
      electricity, 12 horses were trained during 3 weeks in a horse walker with and
      without the use of electricity (3.7 kV). To evaluate the stress response,
      cortisol levels in the blood were measured, the heart rate was monitored using
      the Polar(r) system and the behaviour was evaluated. Neither the cortisol levels
      nor the heart rates showed any relevant statistically significant difference
      between horses moved in the horse walker with or without the use of electricity.
      The highest cortisol levels and heart rates were recorded during the first week
      (habituation period). A significant difference could be observed regarding
      spontaneous compartment changes: while this happened mainly during the first week
      and before the first use of electricity, no horses changed compartments in the
      periods when electricity was used and thereafter. The results of this study
      indicate that the use of electricity in the horse walker does not seem to cause
      significant detectable stress in the horses. 

PMID- 24686817
TI  - [Influence of floor surface and access to pasture on claw characteristics in
      dairy cows kept in cubicle housing systems].
AB  - This study aimed at investigating the effect of the floor type used in the
      walking area of cubicle housing systems and of access to pasture on claw
      dimensions and claw shape in dairy cows. Data were collected on 36 farms, 12
      farms each fitted with mastic asphalt, slatted concrete or solid rubber flooring.
      With each floor type, cows on half of the farms had access to pasture in summer.
      The farms were visited three times at intervals of about 6 months and data were
      collected from 10 cows during each visit. Net growth of the claw horn was highest
      on rubber flooring and lowest on mastic asphalt. On all floor types, claw angles
      were larger after the winter period and smaller after the summer period. With
      regard to claw shape, floor type had an effect on the occurrence of flat, concave
      and overgrown claw soles. In conclusion, none of the investigated floor types was
      clearly superior to the others with regard to claw dimensions and claw shape, and
      access to pasture during summer (median 4 h per day) had only little influence on
      the investigated claw characteristics. 

PMID- 24686818
TI  - [Doramectin intoxication in 3 kittens].
AB  - This case report describes 3 kittens with suspected doramectin toxicity. In a
      litter of 7 kittens treated with doramectin, 3 developed neurological symptoms.
      One kitten showed mild apathy and tremors, while a second one additionally
      presented behavioral changes and seizures that had to be treated with diazepam.
      Both kittens recovered completely. A third kitten was presented to us in coma 3
      days following treatment with doramectin. Subsequently, this kitten developed
      behavioral changes such as aggression, hyperesthesia, tremors, and seizures and
      died 36 hours after presentation. Histopathologic examination of the brain showed
      cytotoxic edema and polioencephalomalacia. The doramectin dosage of the deceased
      kitten was 380 MUg/kg. 

PMID- 24686824
TI  - [Holidays and wage compensation].

PMID- 24686826
TI  - Perception of consonants in reverberation and noise by adults fitted with bimodal
      devices.
AB  - PURPOSE: The purpose of this study was to evaluate the contribution of a
      contralateral hearing aid to the perception of consonants, in terms of voicing,
      manner, and place-of-articulation cues in reverberation and noise by adult
      cochlear implantees aided by bimodal fittings. METHOD: Eight postlingually
      deafened adult cochlear implant (CI) listeners with a fully inserted CI in 1 ear
      and low-frequency hearing in the other ear were tested on consonant perception.
      They were presented with consonant stimuli processed in the following
      experimental conditions: 1 quiet condition, 2 different reverberation times (0.3
      s and 1.0 s), and the combination of 2 reverberation times with a single signal
      to-noise ratio (5 dB). RESULTS: Consonant perception improved significantly when
      listening in combination with a contralateral hearing aid as opposed to listening
      with a CI alone in 0.3 s and 1.0 s of reverberation. Significantly higher scores
      were also noted when noise was added to 0.3 s of reverberation. CONCLUSIONS: A
      considerable benefit was noted from the additional acoustic information in
      conditions of reverberation and reverberation plus noise. The bimodal benefit
      observed was more pronounced for voicing and manner of articulation than for
      place of articulation.

PMID- 24686827
TI  - Causes of death following spinal cord injury during inpatient rehabilitation and
      the first five years after discharge. A Dutch cohort study.
AB  - STUDY DESIGN: Prospective multicentre cohort study. OBJECTIVES: To determine
      mortality, causes and determinants of death of individuals with spinal cord
      injury (SCI) within five years after first inpatient rehabilitation. SETTING: The
      Netherlands. METHODS: Patients were included on admission to first clinical
      rehabilitation after traumatic or nontraumatic SCI. INCLUSION CRITERIA: age
      between 18 and 65, American Spinal Injury Association impairment scale A-D and
      expected long-term wheelchair dependency. Information about survival, cause of
      death, relevant comorbidity and psychosocial circumstances was obtained from the
      rehabilitation physician or general practitioner. Determinants of death were
      retrieved from a prospectively collected database. Deceased persons and survivors
      were compared using chi(2)-test and t-test. Cox regression analysis was performed
      to describe independent predictors of death. The Kaplan-Meier method was used to
      calculate survival curves for independent predictors. Excess mortality was
      described by a standardized mortality ratio (SMR). RESULTS: Mean duration of
      follow up was 6.2 years. A total of 27 persons (12.2%) died during this period
      (SMR 5.3). Main causes of death were cardiovascular disease (37.0%), pulmonary
      disease (29.6%) and neoplasm (14.8%). Older age at injury, nontraumatic SCI,
      family history of cardiovascular disease, less social support and a history of
      other medical conditions on admission were related to death. Older age at injury,
      nontraumatic SCI and a history of other medical conditions were independent
      predictors of death. CONCLUSION: Twelve per cent of persons with SCI who had
      survived the acute hospital phase died during follow up (SMR 5.3). The main
      causes of death were cardiovascular and pulmonary disease.

PMID- 24686825
TI  - Triadic gaze intervention for young children with physical disabilities.
AB  - PURPOSE: This randomized controlled study investigated whether a supplemental
      treatment designed to teach triadic gaze (TG) as a signal of coordinated joint
      attention would yield a significantly greater increase in TG in the experimental
      versus control group. METHOD: Eighteen 10- to 24-month-old children with severe
      motor impairments were randomly assigned to an experimental ( n = 9) or control
      group ( n = 9). For approximately 29 sessions over 17 weeks, experimental
      participants received TG treatment twice weekly with a speech-language
      pathologist in addition to standard practice. Control participants received only
      standard practice from birth-to-three therapists. Coders who were masked to group
      assignment coded TG productions with an unfamiliar speech-language pathologist at
      baseline, every 3 weeks during the experimental phase, and at the final
      measurement session. RESULTS: TG increased across groups from baseline to final
      measurement, with the experimental group showing slightly greater change.
      Performance trends were examined using experimental phase moving averages.
      Comparisons revealed significant differences between groups at 2 time points (at
      12 weeks, r = .30, a medium effect, and at the end of the phase, r = .50, a large
      effect). CONCLUSION: The results suggest the promise of a short-term, focused
      treatment to teach TG as a behavioral manifestation of coordinated joint
      attention to children with severe physical disabilities.

PMID- 24686828
TI  - To cystoscope or not to cystoscope patients with traumatic spinal cord injuries
      managed with indwelling urethral or suprapubic catheters? That is the question!

PMID- 24686829
TI  - 'To cystoscope or not to cystoscope' Was that really the question?

PMID- 24686830
TI  - Dosing of a cued picture-naming treatment for anomia.
AB  - PURPOSE: Recent investigations into effects of intensity or distribution of
      aphasia therapy have provided moderate evidence supporting intensive therapy
      schedules on aphasia treatment response. The purpose of the present study was to
      investigate the feasibility of creating an intensive therapy session without
      extending the amount of daily time a person spends in treatment. METHOD:
      Individuals who presented with chronic anomia poststroke (N = 8) participated in
      2 weeks of a computerized, therapist-delivered, cued, picture-naming treatment.
      Dosing parameters for each session were 8 presentations of 50 pictures, totaling
      400 teaching episodes per session. RESULTS: Of the 8 participants, 6 achieved
      significant increases from baseline on trained items after 400 teaching episodes
      (i.e., 1 treatment hr), and the remaining 2 participants achieved significant
      increases from baseline after 1200 teaching episodes (i.e., 3 treatment hr).
      Maintenance data from 7 of the participants indicated that 6 participants
      maintained significant improvement from baseline on trained items. CONCLUSIONS:
      Given an intensive and saturated context, anomic individuals were surprisingly
      quick at relearning to produce problematic words successfully. Most participants
      demonstrated retention of the gains 2 months after treatment ended. The high
      density of teaching episodes within the treatment session (i.e., the intensive
      treatment schedule) may have contributed to the behavioral gains.

PMID- 24686831
TI  - Nephrogenic adenoma of the urinary bladder: a report of three cases and a review
      of the literature.
AB  - BACKGROUND: Nephrogenic adenoma (NA) is a rare, benign disease of the urinary
      tract, usually as a response to chronic irritation or trauma. Its diagnosis,
      staging, and treatment are not well established. CASE REPORT: We report on 3
      cases of nephrogenic adenoma of the urinary bladder treated in our hospital
      between February 2011 and December 2012 to assess our experience and clinical
      outcome updating and reviewing the literature concerning this issue. All patients
      had undergone previous open urosurgery. Two patients had kidney transplantation.
      Gross hematuria and microhematuria were found in 2 patients. One patient had
      recurrent urinary tract infection. One patient had NA associated with
      transitional cell carcinoma (TCC). Recurrent nephrogenic adenomas were diagnosed
      in 2 patients (time to disease relapse was 5 and 9 months). All nephrogenic
      adenomas and recurrent tumors were treated with transurethral resection.
      CONCLUSIONS: Although NA is a benign metaplastic lesion of the urothelium, its
      recurrence rate is relatively high, thus careful and regular follow-up is
      necessary. Endoscopic characteristics of NA are not specific and a definite
      diagnosis must be made after histological analysis of resected specimens.

PMID- 24686833
TI  - Progress in human immunodeficiency virus care in prisons: still room for
      improvement?

PMID- 24686832
TI  - Identifying Depression in a National Sample of Caregivers Investigated in Regard
      to Their Child's Welfare.
AB  - OBJECTIVES: Identifying depression is the first step in provision of treatment
      across service settings but can be challenging for non-mental health providers.
      This study examined how caseworker identification of depression among parents and
      other caregivers during the child welfare investigation or assessment process
      varies as a function of agency, caseworker, and case characteristics. METHODS:
      Data were drawn from the second National Survey of Child and Adolescent Well
      Being (NSCAW II), a national probability sample of children referred to U.S.
      child welfare agencies between February 2008 and April 2009. The study sample
      comprised 889 parents and other caregivers whose children initially remained at
      home and whose confidential responses on the World Health Organization Composite
      International Diagnostic Interview Short Form indicated a major depressive
      episode within the past 12 months. Weighted logistic regression examined
      predictors of caseworker identification of caregiver depression at the agency,
      caseworker, and case levels. RESULTS: Investigative caseworkers identified mental
      health needs of only 38% of caregivers. Caseworkers were more likely to identify
      caregiver mental health needs when child welfare agency policy specified use of a
      standardized mental health assessment and when the maltreatment report came from
      a health or mental health provider versus other sources, such as teachers or
      family members. Investigative caseloads were negatively associated with
      identifying depression. CONCLUSIONS: Structured mental health assessments may
      help non-mental health professionals identify mental health needs among
      vulnerable populations.

PMID- 24686834
TI  - Webcam delivery of the Lidcombe program for early stuttering: a phase I clinical
      trial.
AB  - PURPOSE: The Lidcombe Program is an operant treatment for early stuttering shown
      with meta-analysis to have a favorable odds ratio. However, many clients are
      unable to access the treatment because of distance and lifestyle factors. In this
      Phase I trial, we explored the potential efficacy, practicality, and viability of
      an Internet webcam Lidcombe Program service delivery model. METHOD: Participants
      were 3 preschool children who stuttered and their parents, all of whom received
      assessment and treatment using webcam in their homes with no clinic attendance.
      RESULTS: At 6 months post-Stage 1 completion, all children were stuttering below
      1.0% syllables stuttered. The webcam intervention was acceptable to the parents
      and appeared to be practical and viable, with only occasional audiovisual
      problems. At present, there is no reason to doubt that a webcam-delivered
      Lidcombe Program will be shown with clinical trials to have comparable efficacy
      with the clinic version. CONCLUSION: Webcam-delivered Lidcombe Program
      intervention is potentially efficacious, is practical and viable, and requires
      further exploration with comparative clinical trials and a qualitative study of
      parent and caregiver experiences.

PMID- 24686835
TI  - Efficient production and purification of recombinant murine kindlin-3 from insect
      cells for biophysical studies.
AB  - Kindlins are essential coactivators, with talin, of the cell surface receptors
      integrins and also participate in integrin outside-in signalling, and the control
      of gene transcription in the cell nucleus. The kindlins are ~75 kDa multidomain
      proteins and bind to an NPxY motif and upstream T/S cluster of the integrin beta
      subunit cytoplasmic tail. The hematopoietically-important kindlin isoform,
      kindlin-3, is critical for platelet aggregation during thrombus formation,
      leukocyte rolling in response to infection and inflammation and osteoclast
      podocyte formation in bone resorption. Kindlin-3's role in these processes has
      resulted in extensive cellular and physiological studies. However, there is a
      need for an efficient method of acquiring high quality milligram quantities of
      the protein for further studies. We have developed a protocol, here described,
      for the efficient expression and purification of recombinant murine kindlin-3 by
      use of a baculovirus-driven expression system in Sf9 cells yielding sufficient
      amounts of high purity full-length protein to allow its biophysical
      characterization. The same approach could be taken in the study of the other
      mammalian kindlin isoforms. 

PMID- 24686836
TI  - Acoustic cues to perception of word stress by English, Mandarin, and Russian
      speakers.
AB  - PURPOSE: This study investigated how listeners' native language affects their
      weighting of acoustic cues (such as vowel quality, pitch, duration, and
      intensity) in the perception of contrastive word stress. METHOD: Native speakers
      (N = 45) of typologically diverse languages (English, Russian, and Mandarin)
      performed a stress identification task on nonce disyllabic words with fully
      crossed combinations of each of the 4 cues in both syllables. RESULTS: The
      results revealed that although the vowel quality cue was the strongest cue for
      all groups of listeners, pitch was the second strongest cue for the English and
      the Mandarin listeners but was virtually disregarded by the Russian listeners.
      Duration and intensity cues were used by the Russian listeners to a significantly
      greater extent compared with the English and Mandarin participants. Compared with
      when cues were noncontrastive across syllables, cues were stronger when they were
      in the iambic contour than when they were in the trochaic contour. CONCLUSIONS:
      Although both English and Russian are stress languages and Mandarin is a tonal
      language, stress perception performance of the Mandarin listeners but not of the
      Russian listeners is more similar to that of the native English listeners, both
      in terms of weighting of the acoustic cues and the cues' relative strength in
      different word positions. The findings suggest that tuning of second-language
      prosodic perceptions is not entirely predictable by prosodic similarities across
      languages.

PMID- 24686837
TI  - A modeled comparison of direct and food web-mediated impacts of common pesticides
      on Pacific salmon.
AB  - In the western United States, pesticides used in agricultural and urban areas are
      often detected in streams and rivers that support threatened and endangered
      Pacific salmon. Although concentrations are rarely high enough to cause direct
      salmon mortality, they can reach levels sufficient to impair juvenile feeding
      behavior and limit macroinvertebrate prey abundance. This raises the possibility
      of direct adverse effects on juvenile salmon health in tandem with indirect
      effects on salmon growth as a consequence of reduced prey abundance. We modeled
      the growth of ocean-type Chinook salmon (Oncorhynchus tshawytscha) at the
      individual and population scales, investigating insecticides that differ in how
      long they impair salmon feeding behavior and in how toxic they are to salmon
      compared to macroinvertebrates. The relative importance of these direct vs.
      indirect effects depends both on how quickly salmon can recover and on the
      relative toxicity of an insecticide to salmon and their prey. Model simulations
      indicate that when exposed to a long-acting organophosphate insecticide that is
      highly toxic to salmon and invertebrates (e.g., chlorpyrifos), the long-lasting
      effect on salmon feeding behavior drives the reduction in salmon population
      growth with reductions in prey abundance having little additional impact. When
      exposed to short-acting carbamate insecticides at concentrations that salmon
      recover from quickly but are lethal to invertebrates (e.g., carbaryl), the
      impacts on salmon populations are due primarily to reductions in their prey. For
      pesticides like carbaryl, prey sensitivity and how quickly the prey community can
      recover are particularly important in determining the magnitude of impact on
      their predators. In considering both indirect and direct effects, we develop a
      better understanding of potential impacts of a chemical stressor on an endangered
      species and identify data gaps (e.g., prey recovery rates) that contribute
      uncertainty to these assessments. 

PMID- 24686838
TI  - Bioefficacy of tea catechins encapsulated in casein micelles tested on a normal
      mouse cell line (4D/WT) and its cancerous counterpart (D/v-src) before and after
      in vitro digestion.
AB  - Numerous studies have demonstrated that tea catechins form complexes with milk
      proteins, especially caseins. Much less work has been conducted to understand the
      metabolic conversions of tea-milk complexes during gastro-duodenal digestion. The
      objective of this study was to determine the significance of this association on
      the digestibility of the milk proteins and on the bioaccessibility of the tea
      polyphenol epigallocatechin gallate (EGCG). An in vitro digestion model mimicking
      the gastric and duodenal phases of the human gastrointestinal tract was employed
      to follow the fate of the milk proteins during digestion and determine the
      bioefficacy of EGCG isolated or encapsulated with the caseins. The samples,
      before and after digestion, were tested using two parallel colonic epithelial
      cell lines, a normal line (4D/WT) and its cancerous transformed counterpart (D/v
      src). EGCG caused a decrease in proliferation of cancer cells, while in normal
      cells, neither isolated nor encapsulated EGCG affected cell proliferation, at
      concentrations <0.15 mg ml(-1). At higher concentrations, both isolated and
      encapsulated produced similar decreases in proliferation. On the other hand, the
      bioefficacy on the cancer cell line showed some differences at lower
      concentrations. The results demonstrated that regardless of the extent of
      digestion of the nanoencapsulated EGCG, the bioefficacy of EGCG was not
      diminished, confirming that casein micelles are an appropriate delivery system
      for polyphenols. 

PMID- 24686839
TI  - Excess counterion condensation on polyelectrolyte kinks and branch points and the
      interaction of skewed charged lines.
AB  - We have developed explicit formulas for the excess number of counterions
      condensed on kinked and intersecting charged lines caused by the more intense
      electric field in the neighborhood of the kink or intersection. As expected, the
      number of additionally bound counterions is greater for more pronounced kinks,
      and also increases with the number of lines that intersect at a common point. We
      have also analyzed the electrostatic interaction potential as a function of
      distance between two charged lines in skewed orientation. Our finding in this
      case is that in a range of close distances the lines must cross a free energy
      barrier in order to separate. 

PMID- 24686840
TI  - Random allocation of pies promotes the evolution of fairness in the Ultimatum
      Game.
AB  - In the Ultimatum Game, two players are offered a chance to win a pie. The
      proposer suggests how to split the pie. The responder can either accept or reject
      the deal. If an agreement is not reached, neither player gets anything. Both game
      theory and evolutionary game theory predict the rational solution that the
      proposer offers the smallest possible share and the responder accepts it.
      Fairness thus requires additional mechanisms for natural selection to favor it.
      Studies to date assumed that individuals have competed for the fixed size of
      pies, in sharp contrast with real situations, where randomness is ubiquitous.
      Here we study the impact of random allocation of pies on the evolution of
      fairness in the Ultimatum Game. Interestingly, we find that the evolution of
      fairness can be promoted by the randomness associated with the size of pies,
      without the support of any additional evolutionary mechanisms. 

PMID- 24686841
TI  - Online learning from input versus offline memory evolution in adult word
      learning: effects of neighborhood density and phonologically related practice.
AB  - PURPOSE: In this study, the authors investigated adult word learning to determine
      how neighborhood density and practice across phonologically related training sets
      influence online learning from input during training versus offline memory
      evolution during no-training gaps. METHOD: Sixty-one adults were randomly
      assigned to learn low- or high-density nonwords. Within each density condition,
      participants were trained on one set of words and then were trained on a second
      set of words, consisting of phonological neighbors of the first set. Learning was
      measured in a picture-naming test. Data were analyzed using multilevel modeling
      and spline regression. RESULTS: Steep learning during input was observed, with
      new words from dense neighborhoods and new words that were neighbors of recently
      learned words (i.e., second-set words) being learned better than other words. In
      terms of memory evolution, large and significant forgetting was observed during 1
      week gaps in training. Effects of density and practice during memory evolution
      were opposite of those during input. Specifically, forgetting was greater for
      high-density and second-set words than for low-density and first-set words.
      CONCLUSION: High phonological similarity, regardless of source (i.e., known words
      or recent training), appears to facilitate online learning from input but seems
      to impede offline memory evolution.

PMID- 24686842
TI  - Role of alveolar topology on acinar flows and convective mixing.
AB  - Due to experimental challenges, computational simulations are often sought to
      quantify inhaled aerosol transport in the pulmonary acinus. Commonly, these are
      performed using generic alveolar topologies, including spheres, toroids, and
      polyhedra, to mimic the complex acinar morphology. Yet, local acinar flows and
      ensuing particle transport are anticipated to be influenced by the specific
      morphological structures. We have assessed a range of acinar models under self
      similar breathing conditions with respect to alveolar flow patterns, convective
      flow mixing, and deposition of fine particles (1.3 MUm diameter). By tracking
      passive tracers over cumulative breathing cycles, we find that irreversible flow
      mixing correlates with the location and strength of the recirculating vortex
      inside the cavity. Such effects are strongest in proximal acinar generations
      where the ratio of alveolar to ductal flow rates is low and interalveolar
      disparities are most apparent. Our results for multi-alveolated acinar ducts
      highlight that fine 1 MUm inhaled particles subject to alveolar flows are
      sensitive to the alveolar topology, underlining interalveolar disparities in
      particle deposition patterns. Despite the simplicity of the acinar models
      investigated, our findings suggest that alveolar topologies influence more
      significantly local flow patterns and deposition sites of fine particles for
      upper generations emphasizing the importance of the selected acinar model. In
      distal acinar generations, however, the alveolar geometry primarily needs to
      mimic the space-filling alveolar arrangement dictated by lung morphology. 

PMID- 24686843
TI  - Cholanamide components for organic alloys; expanding the scope of nanoporous
      steroidal ureas.
AB  - Amide-linked side-chains can substitute for esters in crystalline nanoporous
      steroidal ureas (NSPUs). This efficient conjugation method increases the
      versatility of NPSUs, and should aid the inclusion of complex functional units in
      the crystal channels. 

PMID- 24686844
TI  - A systematic review of treatment outcomes for children with childhood apraxia of
      speech.
AB  - PURPOSE: To present a systematic review of single-case experimental treatment
      studies for childhood apraxia of speech (CAS). METHOD: A search of 9 databases
      was used to find peer-reviewed treatment articles from 1970 to 2012 of all levels
      of evidence with published communication outcomes for children with CAS.
      Improvement rate differences (IRDs) were calculated for articles with replicated
      (n > 1), statistically compared treatment and generalization evidence. RESULTS:
      Forty-two articles representing Phase I and II single-case experimental designs
      (SCEDs; n = 23) or case series or description studies ( n = 19) were analyzed.
      Six articles showed high CAS diagnosis confidence. Of the 13 approaches within
      the 23 SCED articles, treatments were primarily for speech motor skills ( n = 6),
      linguistic skills ( n = 5), or augmentative and alternative communication ( n =
      2). Most participants responded positively to treatment, but only 7 of 13
      approaches in SCED studies reported maintenance and/or generalization of
      treatment effects. Three approaches had preponderant evidence (Smith, 1981). IRD
      effect sizes were calculated for Integral Stimulation/Dynamic Temporal and
      Tactile Cueing, Rapid Syllable Transition Treatment, and Integrated Phonological
      Awareness Intervention. CONCLUSIONS: At least 3 treatments have sufficient
      evidence for Phase III trials and interim clinical practice. In the future,
      efficacy needs to be established via maintenance and generalization measures.

PMID- 24686845
TI  - Hemostasis in brain tumor surgery using the Aquamantys system.
AB  - BACKGROUND: Adequate hemostasis in cranial and spinal tumor surgery is of
      paramount importance in neurosurgical practice. Generalized ooze bleeding from
      the surgical walls cavity, coming from neoplastic vessels or nervous tissue, may
      be problematic. Recent technical advances have dramatically reduced
      intraoperative complications related to blood loss. Several techniques are
      usually employed to control hemostasis in tumor surgery, including preoperative
      embolization, intraoperative hypotension, electrical coagulation, and local
      application of fibrin sealants or hemostatic matrix, which influence coagulation.
      MATERIAL AND METHODS: Our aim in this study was to evaluate the efficacy and the
      safety of the Aquamantys(r) system (Medtronic Advanced Energy, Portsmouth, NH,
      USA), a novel bipolar coagulation device that incorporates a new bipolar
      coagulation technique. This device has been used in 10 consecutive patients
      affected by cerebral tumor along with the standard microsurgical technique and
      well-known intraoperative tools. The technique is associated with simultaneous
      delivery of bipolar radio frequency energy and conductive fluid through its
      electrode tip. The volume of saline passing by the electrode tip prevents
      charring and maintains a clean tip. This cools the tissue as it raises the
      temperature sufficiently to shrink the collagen of veins and arteries. RESULTS:
      Effective hemostasis was achieved in all the cases. No complications or unwanted
      reactions associated with the device have been observed. CONCLUSIONS: Our
      findings suggest that the Aquamantys(r) system may be a highly effective adjuvant
      tool in minimizing blood loss in a patient with brain tumor, as well as reducing
      time of surgery.

PMID- 24686846
TI  - Rare missense variants in POT1 predispose to familial cutaneous malignant
      melanoma.
AB  - Although CDKN2A is the most frequent high-risk melanoma susceptibility gene, the
      underlying genetic factors for most melanoma-prone families remain unknown. Using
      whole-exome sequencing, we identified a rare variant that arose as a founder
      mutation in the telomere shelterin gene POT1 (chromosome 7, g.124493086C>T;
      p.Ser270Asn) in five unrelated melanoma-prone families from Romagna, Italy.
      Carriers of this variant had increased telomere lengths and numbers of fragile
      telomeres, suggesting that this variant perturbs telomere maintenance. Two
      additional rare POT1 variants were identified in all cases sequenced in two
      separate Italian families, one variant per family, yielding a frequency for POT1
      variants comparable to that for CDKN2A mutations in this population. These
      variants were not found in public databases or in 2,038 genotyped Italian
      controls. We also identified two rare recurrent POT1 variants in US and French
      familial melanoma cases. Our findings suggest that POT1 is a major susceptibility
      gene for familial melanoma in several populations. 

PMID- 24686847
TI  - Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes
      associated with upregulated type I interferon signaling.
AB  - The type I interferon system is integral to human antiviral immunity. However,
      inappropriate stimulation or defective negative regulation of this system can
      lead to inflammatory disease. We sought to determine the molecular basis of
      genetically uncharacterized cases of the type I interferonopathy Aicardi
      Goutieres syndrome and of other undefined neurological and immunological
      phenotypes also demonstrating an upregulated type I interferon response. We found
      that heterozygous mutations in the cytosolic double-stranded RNA receptor gene
      IFIH1 (also called MDA5) cause a spectrum of neuroimmunological features
      consistently associated with an enhanced interferon state. Cellular and
      biochemical assays indicate that these mutations confer gain of function such
      that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand
      induced interferon signaling. Our results demonstrate that aberrant sensing of
      nucleic acids can cause immune upregulation. 

PMID- 24686848
TI  - Low copy number of the salivary amylase gene predisposes to obesity.
AB  - Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic
      associations compared to their biallelic counterparts. Here we investigated the
      influence of gene dosage effects on adiposity through a CNV association study of
      gene expression levels in adipose tissue. We identified significant association
      of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body
      mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects.
      Increased AMY1 copy number was positively associated with both amylase gene
      expression (P = 2.31 * 10(-14)) and serum enzyme levels (P < 2.20 * 10(-16)),
      whereas reduced AMY1 copy number was associated with increased BMI (change in BMI
      per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 * 10(-10)) and obesity risk
      (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13
      1.26; P = 1.46 * 10(-10)). The OR value of 1.19 per copy of AMY1 translates into
      about an eightfold difference in risk of obesity between subjects in the top
      (copy number > 9) and bottom (copy number < 4) 10% of the copy number
      distribution. Our study provides a first genetic link between carbohydrate
      metabolism and BMI and demonstrates the power of integrated genomic approaches
      beyond genome-wide association studies. 

PMID- 24686849
TI  - POT1 loss-of-function variants predispose to familial melanoma.
AB  - Deleterious germline variants in CDKN2A account for around 40% of familial
      melanoma cases, and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT
      have also been linked to the disease. Here we set out to identify new high
      penetrance susceptibility genes by sequencing 184 melanoma cases from 105
      pedigrees recruited in the UK, The Netherlands and Australia that were negative
      for variants in known predisposition genes. We identified families where melanoma
      cosegregates with loss-of-function variants in the protection of telomeres 1 gene
      (POT1), with a proportion of family members presenting with an early age of onset
      and multiple primary tumors. We show that these variants either affect POT1 mRNA
      splicing or alter key residues in the highly conserved
      oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein
      telomere binding and leading to increased telomere length. These findings suggest
      that POT1 variants predispose to melanoma formation via a direct effect on
      telomeres. 

PMID- 24686851
TI  - Use of an anatomical scalar to control for sex-based size differences in measures
      of hyoid excursion during swallowing.
AB  - PURPOSE: Traditional methods for measuring hyoid excursion from dynamic
      videofluoroscopy recordings involve calculating changes in position in absolute
      units (mm). This method shows a high degree of variability across studies but
      agreement that greater hyoid excursion occurs in men than in women. Given that
      men are typically taller than women, the authors hypothesized that controlling
      for participant size might neutralize apparent sex-based differences in hyoid
      excursion. METHOD: Hyoid excursion in 20 young (<45) healthy volunteers (10
      male), stratified by height, was measured in a tightly controlled
      videofluoroscopic protocol. RESULTS: The study identified an anatomical scalar
      (C2-C4 length), visible on the videofluoroscopic image, correlated with
      participant height. This scalar differed significantly between men and women. By
      incorporating the anatomical scalar as a continuous covariate in repeated
      measures mixed-model analyses of variance of hyoid excursion, apparent sex-based
      differences were neutralized. Transforming measures of hyoid excursion into
      anatomically scaled units achieved the same result, reducing variation
      attributable to sex-based differences in participant size. CONCLUSIONS: Hyoid
      excursion during swallowing is dependent on a person's size. If measurements do
      not control for this source of variation, apparent sex differences in hyoid
      excursion are seen.

PMID- 24686850
TI  - Genomic and molecular characterization of esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly
      common in certain regions of Asia. Here we report the whole-exome or targeted
      deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number
      variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized
      mutated genes such as FAT1, FAT2, ZNF750 and KMT2D, in addition to those already
      known (TP53, PIK3CA and NOTCH1). Further SCNV evaluation, immunohistochemistry
      and biological analysis suggested their functional relevance in ESCC. Notably,
      RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently
      dysregulated by multiple molecular mechanisms in this cancer. Our approaches also
      uncovered many druggable candidates, and XPO1 was further explored as a
      therapeutic target because it showed both gene mutation and protein
      overexpression. Our integrated study unmasks a number of novel genetic lesions in
      ESCC and provides an important molecular foundation for understanding esophageal
      tumors and developing therapeutic targets. 

PMID- 24686852
TI  - Speech sound production in 2-year-olds who are hard of hearing.
AB  - PURPOSE: The purpose of the study was to (a) compare the speech sound production
      abilities of 2-year-old children who are hard of hearing (HH) to children with
      normal hearing (NH), (b) identify sources of risk for individual children who are
      HH, and (c) determine whether speech sound production skills at age 2 were
      predictive of speech sound production skills at age 3. METHOD: Seventy children
      with bilateral, mild-to-severe hearing loss who use hearing aids and 37 age- and
      socioeconomic status-matched children with NH participated. Children's speech
      sound production abilities were assessed at 2 and 3 years of age. RESULTS: At age
      2, the HH group demonstrated vowel production abilities on par with their NH
      peers but weaker consonant production abilities. Within the HH group, better
      outcomes were associated with hearing aid fittings by 6 months of age, hearing
      loss of less than 45 dB HL, stronger vocabulary scores, and being female.
      Positive relationships existed between children's speech sound production
      abilities at 2 and 3 years of age. CONCLUSION: Assessment of early speech sound
      production abilities in combination with demographic, audiologic, and linguistic
      variables may be useful in identifying HH children who are at risk for delays in
      speech sound production.

PMID- 24686853
TI  - Predictors of mortality and major in-hospital adverse events associated with
      electrophysiology catheter ablation.

PMID- 24686854
TI  - Experimental protocol for manipulating plant-induced soil heterogeneity.
AB  - Coexistence theory has often treated environmental heterogeneity as being
      independent of the community composition; however biotic feedbacks such as plant
      soil feedbacks (PSF) have large effects on plant performance, and create
      environmental heterogeneity that depends on the community composition.
      Understanding the importance of PSF for plant community assembly necessitates
      understanding of the role of heterogeneity in PSF, in addition to mean PSF
      effects. Here, we describe a protocol for manipulating plant-induced soil
      heterogeneity. Two example experiments are presented: (1) a field experiment with
      a 6-patch grid of soils to measure plant population responses and (2) a
      greenhouse experiment with 2-patch soils to measure individual plant responses.
      Soils can be collected from the zone of root influence (soils from the
      rhizosphere and directly adjacent to the rhizosphere) of plants in the field from
      conspecific and heterospecific plant species. Replicate collections are used to
      avoid pseudoreplicating soil samples. These soils are then placed into separate
      patches for heterogeneous treatments or mixed for a homogenized treatment. Care
      should be taken to ensure that heterogeneous and homogenized treatments
      experience the same degree of soil disturbance. Plants can then be placed in
      these soil treatments to determine the effect of plant-induced soil heterogeneity
      on plant performance. We demonstrate that plant-induced heterogeneity results in
      different outcomes than predicted by traditional coexistence models, perhaps
      because of the dynamic nature of these feedbacks. Theory that incorporates
      environmental heterogeneity influenced by the assembling community and additional
      empirical work is needed to determine when heterogeneity intrinsic to the
      assembling community will result in different assembly outcomes compared with
      heterogeneity extrinsic to the community composition. 

PMID- 24686855
TI  - Children's auditory working memory performance in degraded listening conditions.
AB  - PURPOSE: The objectives of this study were to determine (a) whether school-age
      children with typical hearing demonstrate poorer auditory working memory
      performance in multitalker babble at degraded signal-to-noise ratios than in
      quiet; and (b) whether the amount of cognitive demand of the task contributed to
      differences in performance in noise. It was hypothesized that stressing the
      working memory system with the presence of noise would impede working memory
      processes in real time and result in poorer working memory performance in
      degraded conditions. METHOD: Twenty children with typical hearing between 8 and
      10 years old were tested using 4 auditory working memory tasks (Forward Digit
      Recall, Backward Digit Recall, Listening Recall Primary, and Listening Recall
      Secondary). Stimuli were from the standardized Working Memory Test Battery for
      Children. Each task was administered in quiet and in 4-talker babble noise at 0
      dB and -5 dB signal-to-noise ratios. RESULTS: Children's auditory working memory
      performance was systematically decreased in the presence of multitalker babble
      noise compared with quiet. Differences between low-complexity and high-complexity
      tasks were observed, with children performing more poorly on tasks with greater
      storage and processing demands. There was no interaction between noise and
      complexity of task. All tasks were negatively impacted similarly by the addition
      of noise. CONCLUSIONS: Auditory working memory performance was negatively
      impacted by the presence of multitalker babble noise. Regardless of complexity of
      task, noise had a similar effect on performance. These findings suggest that the
      addition of noise inhibits auditory working memory processes in real time for
      school-age children.

PMID- 24686858
TI  - Notes and Records at 75.

PMID- 24686857
TI  - Mediastinectomy for management of chronic pyogranulomatous pleural disease in
      dogs.
AB  - The medical records of 12 dogs with chronic pyogranulomatous pleural disease
      unresponsive to medical management were reviewed retrospectively. Resection of
      the mediastinal pleura (mediastinectomy) was performed through a median
      sternotomy to remove all diseased and surgically accessible mediastinal pleural
      tissue. Dogs were re-examined two weeks postoperatively, and long-term outcome
      was evaluated by contacting owners by phone. Twelve dogs underwent
      mediastinectomy; additional surgeries included subtotal pericardiectomy (8), lung
      lobectomy (4) and partial diaphragmatic resection (2). Histology of resected
      tissue consistently revealed neutrophilic, pyogranulomatous cellulitis/serositis.
      Foreign material was evident in the mediastinal tissue of five dogs and
      microorganisms were recovered from three dogs. Two dogs developed pneumothorax
      immediately postoperatively; one dog developed haemothorax one month
      postoperatively and was euthanased. Median follow-up time was eight months
      (range: 6-43 months); eleven dogs were alive and considered to be symptom-free by
      their owners. Mediastinectomy resulted in complete resolution of symptoms in most
      dogs (92 per cent) and was associated with a low incidence of major
      complications. The results of this study indicated that mediastinectomy results
      in favourable outcome for dogs with chronic pleural pyogranulomatous pleural
      disease unresponsive to medical management.

PMID- 24686856
TI  - Internet-based motivation program for women with eating disorders: eating
      disorder pathology and depressive mood predict dropout.
AB  - BACKGROUND: One of the main problems of Internet-delivered interventions for a
      range of disorders is the high dropout rate, yet little is known about the
      factors associated with this. We recently developed and tested a Web-based 6
      session program to enhance motivation to change for women with anorexia nervosa,
      bulimia nervosa, or related subthreshold eating pathology. OBJECTIVE: The aim of
      the present study was to identify predictors of dropout from this Web program.
      METHODS: A total of 179 women took part in the study. We used survival analyses
      (Cox regression) to investigate the predictive effect of eating disorder
      pathology (assessed by the Eating Disorders Examination-Questionnaire; EDE-Q),
      depressive mood (Hopkins Symptom Checklist), motivation to change (University of
      Rhode Island Change Assessment Scale; URICA), and participants' age at dropout.
      To identify predictors, we used the least absolute shrinkage and selection
      operator (LASSO) method. RESULTS: The dropout rate was 50.8% (91/179) and was
      equally distributed across the 6 treatment sessions. The LASSO analysis revealed
      that higher scores on the Shape Concerns subscale of the EDE-Q, a higher
      frequency of binge eating episodes and vomiting, as well as higher depression
      scores significantly increased the probability of dropout. However, we did not
      find any effect of the URICA or age on dropout. CONCLUSIONS: Women with more
      severe eating disorder pathology and depressive mood had a higher likelihood of
      dropping out from a Web-based motivational enhancement program. Interventions
      such as ours need to address the specific needs of women with more severe eating
      disorder pathology and depressive mood and offer them additional support to
      prevent them from prematurely discontinuing treatment.

PMID- 24686859
TI  - Cytotoxic efficacy of photodynamic therapy in osteosarcoma cells in vitro.
AB  - In recent years, there has been the difficulty in finding more effective
      therapies against cancer with less systemic side effects. Therefore Photodynamic
      Therapy is a novel approach for a more tumor selective treatment. Photodynamic
      Therapy (PDT) that makes use of a nontoxic photosensitizer (PS), which, upon
      activation with light of a specific wavelength in the presence of oxygen,
      generates oxygen radicals that elicit a cytotoxic response(1). Despite its
      approval almost twenty years ago by the FDA, PDT is nowadays only used to treat a
      limited number of cancer types (skin, bladder) and nononcological diseases
      (psoriasis, actinic keratosis)(2). The major advantage of the use of PDT is the
      ability to perform a local treatment, which prevents systemic side effects.
      Moreover, it allows the treatment of tumors at delicate sites (e.g. around nerves
      or blood vessels). Here, an intraoperative application of PDT is considered in
      osteosarcoma (OS), a tumor of the bone, to target primary tumor satellites left
      behind in tumor surrounding tissue after surgical tumor resection. The treatment
      aims at decreasing the number of recurrences and at reducing the risk for
      (postoperative) metastasis. In the present study, we present in vitro PDT
      procedures to establish the optimal PDT settings for effective treatment of
      widely used OS cell lines that are used to reproduce the human disease in well
      established intratibial OS mouse models. The uptake of the PS mTHPC was examined
      with a spectrophotometer and phototoxicity was provoked with laser light
      excitation of mTHPC at 652 nm to induce cell death assessed with a WST-1 assay
      and by the counting of surviving cells. The established techniques enable us to
      define the optimal PDT settings for future studies in animal models. They are an
      easy and quick tool for the evaluation of the efficacy of PDT in vitro before an
      application in vivo. 

PMID- 24686860
TI  - Characteristics of vocal fold vibrations in vocally healthy subjects: analysis
      with multi-line kymography.
AB  - PURPOSE In this study, the authors aimed to analyze longitudinal data from high
      speed digital images in normative subjects using multi-line kymography. METHOD
      Vocally healthy subjects were divided into young (9 men and 17 women; Mage = 27
      years) and older groups (8 men and 12 women; Mage = 73 years). From high-speed
      digital images of phonation at a conversational frequency kymograms were created
      at 5 different levels of the vocal fold and were analyzed to determine the
      opening/closing longitudinal phase difference, open quotient, and speed index.
      Then age- and gender-related differences of these parameters were analyzed
      statistically. RESULTS Young women frequently showed a pattern of posterior-to
      anterior glottal opening and anterior-to-posterior glottal closure, and older
      women demonstrated various opening and closing patterns. Both young men and older
      men were similar to older women. The open quotient was maximal at the most
      posterior glottal level in young women, but it tended to be maximal at the
      anterior glottis in the other subgroups. The mean value of the 5 open quotients
      was largest in young women. The mean speed index had a large negative value in
      older subjects. CONCLUSION This study provides the first information about age
      related differences of longitudinal oscillatory characteristics of the vocal
      folds obtained with high-speed digital imaging. 

PMID- 24686861
TI  - Risky business.

PMID- 24686862
TI  - Patient safety and general practice: traversing the tightrope.

PMID- 24686863
TI  - Assessing, communicating, and managing risk in general practice.

PMID- 24686865
TI  - Probation and mental health: who cares?

PMID- 24686864
TI  - Why are doctors still measuring blood pressure?

PMID- 24686866
TI  - Getting men into medicine.

PMID- 24686867
TI  - Top dietary iron sources in the UK.

PMID- 24686868
TI  - Befriending services for people with sight and hearing loss.

PMID- 24686869
TI  - Shisha: is this addressed within smoking cessation in general practice?

PMID- 24686870
TI  - Patient access again.

PMID- 24686871
TI  - Lady Sybil's death in Downton Abbey: how right and wrong are her doctors?

PMID- 24686872
TI  - The image of general practice: the revolution begins.

PMID- 24686873
TI  - An A-Z of medical philosophy.

PMID- 24686874
TI  - Time ladies and gentlemen! 'This bewitching poison': alcohol and the Royal
      College of Physicians.

PMID- 24686875
TI  - What counts rather than what can be counted: Shoreditch stories.

PMID- 24686876
TI  - Living the dream. The Scottish colourists series: JD Fergusson.

PMID- 24686878
TI  - I am an anarchist.

PMID- 24686879
TI  - The safety of researchers and participants in primary care qualitative research.

PMID- 24686880
TI  - GP careers: changing student perspectives.

PMID- 24686881
TI  - Tips for GP trainees working in rehabilitation medicine.

PMID- 24686882
TI  - Identification of an updated set of prescribing--safety indicators for GPs.
AB  - BACKGROUND: Medication error is an important contributor to patient morbidity and
      mortality and is associated with inadequate patient safety measures. However,
      prescribing-safety tools specifically designed for use in general practice are
      lacking. AIM: To identify and update a set of prescribing-safety indicators for
      assessing the safety of prescribing in general practice, and to estimate the risk
      of harm to patients associated with each indicator. DESIGN AND SETTING: RAND/UCLA
      consensus development of indicators in UK general practice. METHOD: Prescribing
      indicators were identified from a systematic review and previous consensus
      exercise. The RAND Appropriateness Method was used to further identify and
      develop the indicators with an electronic-Delphi method used to rate the risk
      associated with them. Twelve GPs from all the countries of the UK participated in
      the RAND exercise, with 11 GPs rating risk using the electronic-Delphi approach.
      RESULTS: Fifty-six prescribing-safety indicators were considered appropriate for
      inclusion (overall panel median rating of 7-9, with agreement). These indicators
      cover hazardous prescribing across a range of therapeutic indications, hazardous
      drug-drug combinations and inadequate laboratory test monitoring. Twenty-three
      (41%) of these indicators were considered high risk or extreme risk by 80% or
      more of the participants. CONCLUSION: This study identified a set of 56
      indicators that were considered, by a panel of GPs, to be appropriate for
      assessing the safety of GP prescribing. Twenty-three of these indicators were
      considered to be associated with high or extreme risk to patients and should be
      the focus of efforts to improve patient safety.

PMID- 24686883
TI  - High-risk use of over-the-counter non-steroidal anti-inflammatory drugs: a
      population-based cross-sectional study.
AB  - BACKGROUND: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is
      associated with serious adverse drug events (ADEs). AIM: To determine the
      prevalence of over-the-counter (OTC) NSAID use in the general population and in
      patients with a high risk of developing a serious NSAID-related ADE. DESIGN AND
      SETTING: Cross-sectional study in four general practices in the Netherlands.
      METHOD: Two patient samples were selected: a random sample of adults (general
      population sample); and adult patients with a high risk of developing a serious
      ADE in case of NSAID use (high-risk sample). All included patients were sent a
      questionnaire regarding their use of OTC NSAIDs in the 4 weeks prior to
      participation. RESULTS: In the general population sample, 118 of 456 (26%)
      invited patients completed the questionnaire. Of these, 35 (30%) had used an OTC
      NSAID. In the high-risk sample, 264 of 713 (37%) invited patients completed the
      questionnaire, and of these high-risk patients 33 (13%) had used an OTC NSAID.
      Over 20% of OTC NSAID users in the general population sample and over 30% in the
      high-risk sample had used the OTC NSAID for >7 days. OTC NSAIDs were used in a
      dosage exceeding the recommended daily maximum by 9% and 3% of OTC NSAID users in
      the general population and the high-risk sample respectively. CONCLUSION: OTC
      NSAIDs are used by almost one-third of the general population. In the high-risk
      patients selected, one in eight patients used an OTC NSAID. Continued efforts by
      health authorities and healthcare professionals to inform patients of the risks
      of these drugs are warranted.

PMID- 24686884
TI  - Communicating risk using absolute risk reduction or prolongation of life formats:
      cluster-randomised trial in general practice.
AB  - BACKGROUND: It is important that patients are well-informed about risks and
      benefits of therapies to help them decide whether to accept medical therapy.
      Different numerical formats can be used in risk communication but It remains
      unclear how the different formats affect decisions made by real-life patients.
      AIM: To compare the impact of using Prolongation Of Life (POL) and Absolute Risk
      Reduction (ARR) information formats to express effectiveness of cholesterol
      lowering therapy on patients' redemptions of statin prescriptions, and on
      patients' confidence in their decision and satisfaction with the risk
      communication. DESIGN AND SETTING: Cluster-randomised clinical trial in general
      practices. Thirty-four Danish GPs from 23 practices participated in a primary
      care-based clinical trial concerning use of quantitative effectiveness formats
      for risk communication in health prevention consultations. METHOD: GPs were
      cluster-randomised (treating practices as clusters) to inform patients about
      cardiovascular mortality risk and the effectiveness of statin treatment using
      either POL or ARR formats. Patients' redemptions of statin prescriptions were
      obtained from a regional prescription database. The COMRADE questionnaire was
      used to measure patients' confidence in their decision and satisfaction with the
      risk communication. RESULTS: Of the 240 patients included for analyses, 112 were
      allocated to POL information and 128 to ARR. Patients redeeming a statin
      prescription totalled six (5.4%) when informed using POL, and 32 (25.0%) when
      using ARR. The level of confidence in decision and satisfaction with risk
      communication did not differ between the risk formats. CONCLUSION: Patients
      redeemed statin prescriptions less often when their GP communicated treatment
      effectiveness using POL compared with ARR.

PMID- 24686885
TI  - Change in cardiovascular risk factors following early diagnosis of type 2
      diabetes: a cohort analysis of a cluster-randomised trial.
AB  - BACKGROUND: There is little evidence to inform the targeted treatment of
      individuals found early in the diabetes disease trajectory. AIM: To describe
      cardiovascular disease (CVD) risk profiles and treatment of individual CVD risk
      factors by modelled CVD risk at diagnosis; changes in treatment, modelled CVD
      risk, and CVD risk factors in the 5 years following diagnosis; and how these are
      patterned by socioeconomic status. DESIGN AND SETTING: Cohort analysis of a
      cluster-randomised trial (ADDITION-Europe) in general practices in Denmark,
      England, and the Netherlands. METHOD: A total of 2418 individuals with screen
      detected diabetes were divided into quartiles of modelled 10-year CVD risk at
      diagnosis. Changes in treatment, modelled CVD risk, and CVD risk factors were
      assessed at 5 years. RESULTS: The largest reductions in risk factors and modelled
      CVD risk were seen in participants who were in the highest quartile of modelled
      risk at baseline, suggesting that treatment was offered appropriately.
      Participants in the lowest quartile of risk at baseline had very similar levels
      of modelled CVD risk at 5 years and showed the least variation in change in
      modelled risk. No association was found between socioeconomic status and changes
      in CVD risk factors, suggesting that treatment was equitable. CONCLUSION:
      Diabetes management requires setting of individualised attainable targets. This
      analysis provides a reference point for patients, clinicians, and policymakers
      when considering goals for changes in risk factors early in the course of the
      disease that account for the diverse cardiometabolic profile present in
      individuals who are newly diagnosed with type 2 diabetes.

PMID- 24686886
TI  - Oral penicillin prescribing for children in the UK: a comparison with BNF for
      Children age-band recommendations.
AB  - BACKGROUND: The British National Formulary for Children (BNFC) recommends dosing
      oral penicillins according to age-bands, weight-bands, or weight-based
      calculations. Because of the rising prevalence of childhood obesity, age-band
      based prescribing could lead to subtherapeutic dosing. AIM: To investigate actual
      oral penicillin prescribing by GPs in the UK with reference to the current BNFC
      age-band recommendations. DESIGN AND SETTING: Descriptive analysis of UK
      prescriptions in the 2010 IMS Disease-Analyzer database (IMS-DA). METHOD: A
      detailed database analysis was undertaken of oral penicillin prescriptions for 0
      18 year olds from the 2010 IMS-DA. The prescription analysis included all
      available data on formulation, strength (mg), prescription quantity unit, package
      size, prescribed quantity, and volume. RESULTS: Considering amoxicillin alone, no
      infants (aged <1 year) were prescribed the BNFC 2011 edition recommended unit
      dose (62.5 mg), while the majority received double the dose (125 mg); among
      children aged 1-5 years, 96% were prescribed the recommended unit dose (125 mg),
      but 40% of 6-12 year olds and 70% of 12-18 year olds were prescribed unit doses
      below the BNFC recommendations. For otitis media, only those children aged <1
      year received the recommended dose of amoxicillin (40-90 mg/kg/day). Similar
      variations in dosing across age-bands were observed for phenoxymethylpenicillin
      and flucloxacillin. CONCLUSION: There is wide variation in the dosing of
      penicillins for children in UK primary care, with very few children being
      prescribed the current national recommended doses. There is an urgent need to
      review dosing guidelines, in relation to the weights of children today.

PMID- 24686887
TI  - Doctors record higher blood pressures than nurses: systematic review and meta
      analysis.
AB  - BACKGROUND: The magnitude of the 'white coat effect', the alerting rise in blood
      pressure, is greater for doctors than nurses. This could bias interpretation of
      studies on nurse-led care in hypertension, and risks overestimating or
      overtreating high blood pressure by doctors in clinical practice. AIM: To
      quantify differences between blood pressure measurements made by doctors and
      nurses. DESIGN AND SETTING: Systematic review and meta-analysis using searches of
      MEDLINE, CENTRAL, CINAHL, Embase, journal collections, and conference abstracts.
      METHOD: Studies in adults reporting mean blood pressures measured by doctors and
      nurses at the same visit were selected, and mean blood pressures extracted, by
      two reviewers. Study risk of bias was assessed using modified Cochrane criteria.
      Outcomes were pooled across studies using random effects meta-analysis. RESULTS:
      In total, 15 studies (11 hypertensive; four mixed hypertensive and normotensive
      populations) were included from 1899 unique citations. Compared with doctors'
      measurements, nurse-measured blood pressures were lower (weighted mean
      differences: systolic -7.0 [95% confidence interval {CI} = -4.7 to -9.2] mmHg,
      diastolic -3.8 [95% CI = -2.2 to -5.4] mmHg). For studies at low risk of bias,
      differences were lower: systolic -4.6 (95% CI = -1.9 to -7.3) mmHg; diastolic 
      1.7 (95% CI = -0.1 to -3.2) mmHg. White coat hypertension was diagnosed more
      frequently based on doctors' than on nurses' readings: relative risk 1.6 (95% CI
      =1.2 to 2.1). CONCLUSIONS: The white coat effect is smaller for blood pressure
      measurements made by nurses than by doctors. This systematic difference has
      implications for hypertension diagnosis and management. Caution is required in
      pooling data from studies using both nurse- and doctor-measured blood pressures.

PMID- 24686889
TI  - Attention deficit hyperactivity disorder: clinical update.

PMID- 24686888
TI  - Clinical prediction rules in practice: review of clinical guidelines and survey
      of GPs.
AB  - BACKGROUND: The publication of clinical prediction rules (CPRs) studies has risen
      significantly. It is unclear if this reflects increasing usage of these tools in
      clinical practice or how this may vary across clinical areas. AIM: To review
      clinical guidelines in selected areas and survey GPs in order to explore CPR
      usefulness in the opinion of experts and use at the point of care. DESIGN AND
      SETTING: A review of clinical guidelines and survey of UK GPs. METHOD: Clinical
      guidelines in eight clinical domains with published CPRs were reviewed for
      recommendations to use CPRs including primary prevention of cardiovascular
      disease, transient ischaemic attack (TIA) and stroke, diabetes mellitus, fracture
      risk assessment in osteoporosis, lower limb fractures, breast cancer, depression,
      and acute infections in childhood. An online survey of 401 UK GPs was also
      conducted. RESULTS: Guideline review: Of 7637 records screened by title and/or
      abstract, 243 clinical guidelines met inclusion criteria. CPRs were most commonly
      recommended in guidelines regarding primary prevention of cardiovascular disease
      (67%) and depression (67%). There was little consensus across various clinical
      guidelines as to which CPR to use preferentially. SURVEY: Of 401 responders to
      the GP survey, most were aware of and applied named CPRs in the clinical areas of
      cardiovascular disease and depression. The commonest reasons for using CPRs were
      to guide management and conform to local policy requirements. CONCLUSION: GPs use
      CPRs to guide management but also to comply with local policy requirements.
      Future research could focus on which clinical areas clinicians would most benefit
      from CPRs and promoting the use of robust, externally validated CPRs.

PMID- 24686890
TI  - The filtered words test and the influence of lexicality.
AB  - PURPOSE: In the present study, the authors aimed to investigate the language
      confounds of filtered words tests by examining the repetition of real words
      versus nonsense words as a function of level of filtering. METHOD: Fifty-five
      young, native-English-speaking women with normal hearing were required to repeat
      80 real-word and 80 nonsense-word monosyllables that were matched for phonemic
      content and low-pass filtered. Thirty participants were tested using a harsher
      filter range of 2000 to 500 Hz, and 25 participants were tested using a milder
      filter range of 3000 to 1500 Hz. RESULTS: Paired-sample t tests compared accuracy
      (percentage of phonemes correct) for word and nonsense-word stimuli at each
      filter level. At filter levels between 3000 and 1750 Hz, performance for word
      stimuli was significantly better than for nonsense-word stimuli. Conversely, at
      filter levels between 500 and 1250 Hz, performance was significantly better for
      nonsense words. CONCLUSIONS: The linguistic content of real-word stimuli benefits
      performance on low-pass filtered speech tests at filter levels above 1500 Hz.
      Caution must be taken when using real-word stimuli in low-pass filtered speech
      tests as part of an auditory processing diagnostic test battery, because language
      ability will impact on performance.

PMID- 24686891
TI  - Phenolic extracts of Rubus ulmifolius Schott flowers: characterization,
      microencapsulation and incorporation into yogurts as nutraceutical sources.
AB  - Rubus ulmifolius Schott (Rosaceae), known as wild blackberry, is a perennial
      shrub found in wild and cultivated habitats in Europe, Asia and North Africa.
      Traditionally, it is used for homemade remedies because of its medicinal
      properties, including antioxidant activity. In the present work, phenolic
      extracts of R. ulmifolius flower buds obtained by decoction and hydroalcoholic
      extraction were chemically and biologically characterized. Several phenolic
      compounds were identified in both decoction and hydroalcoholic extracts of
      flowers, ellagitannin derivatives being the most abundant ones, namely the
      sanguiin H-10 isomer and lambertianin. Additionally, comparing with the decoction
      form, the hydroalcoholic extract presented both higher phenolic content and
      antioxidant activity. The hydroalcoholic extract was thereafter microencapsulated
      in an alginate-based matrix and incorporated into a yogurt to achieve antioxidant
      benefits. In what concerns the performed incorporation tests, the obtained
      results pointed out that, among the tested samples, the yoghurt containing the
      microencapsulated extract presented a slightly higher antioxidant activity, and
      that both forms (free and microencapsulated extracts) gave rise to products with
      higher activity than the control. In conclusion, this study demonstrated the
      antioxidant potential of the R. ulmifolius hydroalcoholic extract and the
      effectiveness of the microencapsulation technique used for its preservation, thus
      opening new prospects for the exploitation of these natural phenolic extracts in
      food applications. 

PMID- 24686892
TI  - Integrated training for aphasia: an application of part-whole learning to treat
      lexical retrieval, sentence production, and discourse-level communications in
      three cases of nonfluent aphasia.
AB  - PURPOSE: The purpose of this study was to evaluate integrated training for
      aphasia (ITA), a multicomponent language-production treatment based on part-whole
      learning that systematically trains lexical retrieval, sentence production, and
      discourse-level communications. Specific research objectives were to evaluate
      acquisition of target structures, statistical parameters associated with learning
      variables, treatment generalization, and the efficacy of individual treatment
      components. METHOD: ITA was administered to 3 individuals with nonfluent aphasia
      following a multiple-baseline, across-behaviors design. Effect size and
      correlational coefficients were computed to assess acquisition, generalization,
      and maintenance of target structures. Standardized tests and a treatment efficacy
      questionnaire were also completed. RESULTS: A significant treatment effect was
      found in 2 of the 3 participants. In addition, as is seen in normal skill
      acquisition, practice time and error rate were significantly correlated. All
      participants demonstrated evidence of generalization on standardized language
      measures. Only 1 participant improved, however, on the communication measures.
      Results of the treatment component analysis revealed significant differences in
      the perceived efficacy of individual therapy tasks. CONCLUSIONS: Findings add to
      the evidence supporting multicomponent aphasia treatments, provide preliminary
      support for ITA and the application of a part-whole learning approach, and
      suggest that specific treatment components may contribute differentially to
      outcomes and generalization effects.

PMID- 24686893
TI  - A guide on how to develop an International Classification of Functioning,
      Disability and Health Core Set.
AB  - International Classification of Functioning, Disability and Health (ICF) Core
      Sets are purpose-tailored shortlists of ICF categories from the whole ICF
      classification for describing functioning and disability. Although the 34 ICF
      Core Sets developed up to now already cover many health conditions, there may
      still be a need to develop additional ICF Core Sets that tackle other health
      conditions and address other purposes. This paper provides a detailed description
      of the standard process for developing ICF Core Sets that will serve as a guide
      for future ICF Core Set development projects. ICF Core Sets are developed by
      means of a three-phase, multi-method scientific process. The process involves
      four preparatory studies - an empirical multicentre study, a systematic
      literature review, a qualitative study and an expert survey. The results of the
      preparatory studies serve as the starting point for a structured decision-making
      and consensus process at an international conference, during which participating
      experts decide on the ICF categories to be included in the Comprehensive and
      Brief ICF Core Sets. The first version of the ICF Core Set may necessitate
      modifications for specific applications and implementation in specific settings. 

PMID- 24686894
TI  - Plasmonic excitations of 1D metal-dielectric interfaces in 2D systems: 1D surface
      plasmon polaritons.
AB  - Surface plasmon-polariton (SPP) excitations of metal-dielectric interfaces are a
      fundamental light-matter interaction which has attracted interest as a route to
      spatial confinement of light far beyond that offered by conventional dielectric
      optical devices. Conventionally, SPPs have been studied in noble-metal
      structures, where the SPPs are intrinsically bound to a 2D metal-dielectric
      interface. Meanwhile, recent advances in the growth of hybrid 2D crystals, which
      comprise laterally connected domains of distinct atomically thin materials,
      provide the first realistic platform on which a 2D metal-dielectric system with a
      truly 1D metal-dielectric interface can be achieved. Here we show for the first
      time that 1D metal-dielectric interfaces support a fundamental 1D plasmonic mode
      (1DSPP) which exhibits cutoff behavior that provides dramatically improved light
      confinement in 2D systems. The 1DSPP constitutes a new basic category of plasmon
      as the missing 1D member of the plasmon family: 3D bulk plasmon, 2DSPP, 1DSPP,
      and 0D localized SP. 

PMID- 24686895
TI  - Dietary flavonoid intake and thyroid cancer risk in the NIH-AARP diet and health
      study.
AB  - Experimental studies suggested that flavonoids may influence thyroid
      carcinogenesis, but epidemiologic evidence is sparse. No study has examined
      different classes of flavonoids in relation to thyroid cancer risk. Using data
      from the NIH-AARP Diet and Health Study, which enrolled 491,840 U.S. men and
      women, ages 50 to 71 years at baseline, we prospectively examined the risk of
      thyroid cancer in relation to dietary intakes of catechins, flavanones,
      flavonols, anthocyanidins, flavones, isoflavones, and total flavonoids. Dietary
      intakes were assessed using a food frequency questionnaire. Cancer cases were
      ascertained by linkage to state cancer registries. Multivariable-adjusted Cox
      proportional hazard models were used to estimate HRs and 95% confidence intervals
      (CI). During follow up (mean = 9 years), we identified 586 thyroid cancer cases.
      Thyroid cancer risk was inversely associated with dietary flavan-3-ols [HRQ5 vs.
      Q1 (95% CI): 0.70 (0.55, 0.91), PTrend = 0.03], but positively associated with
      flavanones [HRQ5 vs. Q1 (95% CI): 1.50 (1.14, 1.96), PTrend = 0.004]. Other
      classes of flavonoids and total flavonoids were not associated with thyroid
      cancer risk. Similar associations were found for papillary thyroid cancer. Our
      findings suggest that dietary intake of different classes of dietary flavonoids
      may have divergent effects on thyroid cancer risk. More studies are needed to
      clarify a role of flavonoids in thyroid cancer development. Results from our
      study suggest a potential nutritional etiology of thyroid cancer. Cancer
      Epidemiol Biomarkers Prev; 23(6); 1102-8. (c)2014 AACR. 

PMID- 24686897
TI  - Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy
      of irradiation and can be augmented by CTLA-4 blockade in a mouse model.
AB  - PURPOSE: There is growing evidence that tumor-specific immune responses play an
      important role in anti-cancer therapy, including radiotherapy. Using mouse tumor
      models we demonstrate that irradiation-induced anti-tumor immunity is essential
      for the therapeutic efficacy of irradiation and can be augmented by modulation of
      cytotoxic T lymphocyte (CTL) activity. METHODS AND MATERIALS: C57BL/6 mice,
      syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used.
      Cells were injected into the right femurs of mice. Ten days after inoculation,
      tumors were treated with 30 Gy of local X-ray irradiation and their growth was
      subsequently measured. The effect of irradiation on tumor growth delay (TGD) was
      defined as the time (in days) for tumors to grow to 500 mm3 in the treated group
      minus that of the untreated group. Cytokine production and serum antibodies were
      measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors
      were locally controlled by X-ray irradiation and re-introduced EL4 cells were
      completely rejected. Mouse EL4-specific systemic immunity was confirmed by
      splenocyte cytokine production and detection of tumor-specific IgG1 antibodies.
      In the LL/C tumor model, X-ray irradiation also significantly delayed tumor
      growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days
      (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti
      CD8 antibody significantly decreased the therapeutic efficacy of irradiation
      (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation
      affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly
      increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to
      19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy.
      CONCLUSIONS: Our results indicate that tumor-specific immune responses play an
      important role in the therapeutic efficacy of irradiation. Immunomodulation,
      including CTLA-4 blockade, may be a promising treatment in combination with
      radiotherapy.

PMID- 24686896
TI  - Persistent pain facilitates response to morphine reward by downregulation of
      central amygdala GABAergic function.
AB  - Opioid-based analgesics are widely used for treating chronic pain, but opioids
      are highly addictive when repeatedly used because of their strong rewarding
      effects. In recent years, abuse of prescription opioids has dramatically
      increased, including incidences of misuse of opioid drugs prescribed for pain
      control. Despite this issue in current clinical pain management, it remains
      unknown how pain influences the abuse liability of prescription opioids. Pain as
      aversive experience may affect opioid reward of positive emotion through common
      brain sites involved in emotion processing. In this study, on a rat model of
      chronic pain, we determined how persistent pain altered behavioral responses to
      morphine reward measured by the paradigm of unbiased conditioned place preference
      (CPP), focusing on GABAergic synaptic activity in neurons of the central nucleus
      of the amygdala (CeA), an important brain region for emotional processing of both
      pain and reward. We found that pain reduced the minimum number of morphine
      conditioning sessions required for inducing CPP behavior. Both pain and morphine
      conditioning that elicited CPP inhibited GABA synaptic transmission in CeA
      neurons. Pharmacological activation of CeA GABAA receptors reduced the pain and
      inhibited CPP induced both by an effective dose of morphine and by a sub
      threshold dose of morphine under pain condition. Furthermore, inhibition of CeA
      GABAA receptors mimicked the pain effect, rendering the sub-threshold dose of
      morphine effective in CPP induction. These findings suggest that pain facilitates
      behavioral responses to morphine reward by predisposing the inhibitory GABA
      function in the CeA circuitry involved in the behavior of opioid reward. 

PMID- 24686898
TI  - Preparation of light-responsive membranes by a combined surface grafting and
      postmodification process.
AB  - In order to modify the surface tension of commercial available track-edged
      polymer membranes, a procedure of surface-initiated polymerization is presented.
      The polymerization from the membrane surface is induced by plasma treatment of
      the membrane, followed by reacting the membrane surface with a methanolic
      solution of 2-hydroxyethyl methacrylate (HEMA). Special attention is given to the
      process parameters for the plasma treatment prior to the polymerization on the
      surface. For example, the influence of the plasma-treatment on different types of
      membranes (e.g. polyester, polycarbonate, polyvinylidene fluoride) is studied.
      Furthermore, the time-dependent stability of the surface-grafted membranes is
      shown by contact angle measurements. When grafting poly(2-hydroxyethyl
      methacrylate) (PHEMA) in this way, the surface can be further modified by
      esterification of the alcohol moiety of the polymer with a carboxylic acid
      function of the desired substance. These reactions can therefore be used for the
      functionalization of the membrane surface. For example, the surface tension of
      the membrane can be changed or a desired functionality as the presented light
      responsiveness can be inserted. This is demonstrated by reacting PHEMA with a
      carboxylic acid functionalized spirobenzopyran unit which leads to a light
      responsive membrane. The choice of solvent plays a major role in the
      postmodification step and is discussed in more detail in this paper. The
      permeability measurements of such functionalized membranes are performed using a
      Franz cell with an external light source. By changing the wavelength of the light
      from the visible to the UV-range, a change of permeability of aqueous caffeine
      solutions is observed.

PMID- 24686899
TI  - Do physicians spend less time with patients in contact isolation?: a time-motion
      study of internal medicine interns.

PMID- 24686900
TI  - Detection and quantification of the Bcr/Abl chimeric protein on biochips using
      LDI-TOF MS.
AB  - The Bcr/Abl chimeric protein was captured by two antibodies, anti-Bcr on gold
      nanoparticles (AuNPs) and anti-Abl on a biochip, in a sandwich assay format. The
      presence of the Bcr/Abl in cells was then verified by amplified LDI-TOF MS
      signals, and relative amounts were quantified using AuNPs coated with deuterated
      alkanethiols as an internal standard. 

PMID- 24686901
TI  - Perception of speech produced by native and nonnative talkers by listeners with
      normal hearing and listeners with cochlear implants.
AB  - PURPOSE The aim of this study was to evaluate the understanding of English
      sentences produced by native (English) and nonnative (Spanish) talkers by
      listeners with normal hearing (NH) and listeners with cochlear implants (CIs).
      METHOD Sentence recognition in noise was measured in adult subjects with CIs and
      subjects with NH, all of whom were native talkers of American English. Test
      sentences were from the Hearing in Noise Test (HINT) database and were produced
      in English by four native and eight nonnative talkers. Subjects also rated the
      intelligibility and accent for each talker. RESULTS The speech recognition
      thresholds in noise of subjects with CIs and subjects with NH were 4.23 dB and
      1.32 dB poorer with nonnative talkers than with native talkers, respectively.
      Performance was significantly correlated with talker intelligibility and accent
      ratings for subjects with CIs but only correlated with talker intelligibility
      ratings for subjects with NH. For all subjects, performance with individual
      nonnative talkers was significantly correlated with talkers' number of years of
      residence in the United States. CONCLUSION CI users exhibited a larger deficit in
      speech understanding with nonnative talkers than did subjects with NH, relative
      to native talkers. Nonnative talkers' experience with native culture contributed
      strongly to speech understanding in noise, intelligibility ratings, and accent
      ratings of both listeners with NH and listeners with CIs. 

PMID- 24686902
TI  - A computational analysis of the deformation of the femoropopliteal artery with
      stenting.
AB  - Physiological loads that act on the femoropopliteal artery, in combination with
      stenting, can lead to uncharacteristic deformations of the stented vessel. The
      overall goal of this study was to investigate the effect of stent length and
      stent location on the deformation characteristics of the superficial femoral
      artery (SFA) using an anatomically accurate, three-dimensional finite element
      model of the leg. For a range of different stent lengths and locations, the
      deformation characteristics (length change, curvature change, and axial twist)
      that result from physiological loading of the SFA along with the mechanical
      behavior of the vessel tissue are investigated. Results showed that stenting
      portions of the SFA leads to a change in global deformation characteristics of
      the vessel. Increased stress and strain values and altered deformation
      characteristics were observed in the various stented cases of this study, which
      are compared to previous results of an unstented vessel. The study concludes that
      shortening, twist and curvature characteristics of the stented vessel are
      dependent on stent length and stent location within the vessel.

PMID- 24686904
TI  - Treatments for avascular necrosis of the talus: a systematic review.
AB  - INTRODUCTION: Avascular necrosis (AVN) of the talus is a challenging entity to
      treat. Poor outcomes remain all too common. The purpose of this systematic review
      was to: identify and summarize all available evidence for the treatment of talar
      AVN; provide treatment recommendations; and highlight gaps in the literature.
      METHODS: We searched MEDLINE and EMBASE using a unique algorithm. The Oxford
      Level of Evidence Guidelines and GRADE recommendations were used to rate the
      quality of evidence and to make treatment recommendations. RESULTS: 19 studies
      fit the inclusion criteria constituting 321 ankles at final follow-up. The
      interventions of interest included hindfoot fusion, conservative measures, bone
      grafting, vascularized bone graft, core decompression, and talar replacement. All
      studies were Level IV evidence. Due to study quality, imprecise and sparse data,
      and potential for reporting bias, the quality of evidence is "very low". Studies
      investigating conservative therapy showed that prolonged protective weight
      bearing provides the best outcomes in early talar AVN. DISCUSSION: Given the
      "very low" GRADE recommendation, understanding of talar AVN would be
      significantly altered by higher quality studies. Early talar AVN seems best
      treated with protected weightbearing and possibly in combination with ESWT. If
      that fails, core decompression may be an attractive treatment option. Arthrodesis
      should be saved as a salvage procedure. Future prospective, randomized studies
      are necessary to guide the conservative and surgical management of talar AVN.
      LEVEL OF EVIDENCE: Level II.

PMID- 24686905
TI  - Subtalar joint stress imaging with tomosynthesis.
AB  - The purpose of this study was to perform stress imaging of hindfoot inversion and
      eversion using tomosynthesis and to assess the subtalar joint range of motion
      (ROM) of healthy subjects. The subjects were 15 healthy volunteers with a mean
      age of 29.1 years. Coronal tomosynthesis stress imaging of the subtalar joint was
      performed in a total of 30 left and right ankles. A Telos stress device was used
      for the stress load, and the load was 150 N for both inversion and eversion.
      Tomographic images in which the posterior talocalcaneal joint could be confirmed
      on the neutral position images were used in measurements. The angle of the
      intersection formed by a line through the lateral articular facet of the
      posterior talocalcaneal joint and a line through the surface of the trochlea of
      the talus was measured. The mean change in the angle of the calcaneus with
      respect to the talus was 10.3 +/- 4.8 degrees  with inversion stress and 5.0 +/-
      3.8 degrees  with eversion stress from the neutral position. The result was a
      clearer depiction of the subtalar joint, and inversion and eversion ROM of the
      subtalar joint was shown to be about 15 degrees  in healthy subjects. LEVELS OF
      EVIDENCE: Diagnostic, Level IV.

PMID- 24686906
TI  - Effects of total ankle arthroplasty training course on physician practice
      patterns and complication rates.
AB  - BACKGROUND: The purpose of this retrospective survey study was to determine the
      short-term effects of the AAOS/AOFAS total ankle arthroplasty (TAA) training
      course on participant practice patterns, implant preferences, and complication
      rates. METHODS: An anonymous digital survey was administered via email to all
      2012 and 2013 participants. Data regarding industry courses attended, implant
      system preferences, surgical indications, case volume, patient age, complication
      rates, and overall perceptions of TAA in the three months before and after the
      course were collected and analyzed. RESULTS: Of the 87 participants contacted, 43
      (49%) completed the entire survey. STAR (Small Bone Innovations, Inc.,
      Morrisville, PA) was the most preferred implant before the course with 15
      individuals listing it as top preference. A large percentage of participants
      (67%) changed implant preferences after the course. Of the 29 participants who
      changed preferences, 48% switched to INBONE II (Wright Medical, Arlington, TN)
      and 24% to STAR. Average number of TAAs performed in the 3 months before the
      course was 1.3 and increased significantly in the following 3 months to 2.1.
      Total number of reported intraoperative complications decreased from 12 before
      the course to 6 after, the most common being malleolar fractures. Overall, 84% of
      participants indicated that the course positively changed their use and
      perceptions of TAA and current implant systems. CONCLUSION: The main finding of
      this study was that the AAOS/AOFAS TAA training course changed implant system
      preferences, surgical indications, number of cases performed, and complication
      rates among participants in the short-term.

PMID- 24686907
TI  - Imaging of tarsal navicular disorders: a pictorial review.
AB  - The tarsal navicular is a bone within the midfoot that plays a critical role in
      maintaining the arch of the foot. This bone is clinically relevant because it may
      be affected by a wide array of pathologies. Our approach includes a detailed
      description of the imaging characteristics and disorders affecting the tarsal
      navicular. Organization includes (a) normal imaging, (b) accessory ossicles, (c)
      coalition, (d) fractures, (e) Kohler's disease, (f) osteonecrosis, (g)
      osteochondral lesions, (h) arthropathies, and (i) tumors. The purpose of this
      article is to discuss normal variants and pathological processes that can affect
      the tarsal navicular, with emphasis on the often-overlooked imaging findings. 

PMID- 24686908
TI  - Open fracture dislocation of the talus with total extrusion: a case report.
AB  - Open fractures with complete extrusion of talus are high-energy injuries. While
      treating these injuries, union of the fracture, vascularity of the body, and
      possibility of infection are main issues predicting less favorable outcomes. At
      present, there are no recommended treatment protocols for the management of such
      injuries. Early debridement, wound care, anatomic reduction, and adequate
      fixation are key factors in the management of compound injuries of the talus.
      There are few reports in the literature on successful reimplantation of talus
      when it is completely extruded. Encouraging functional outcomes of reimplantation
      of extruded talus suggest that excision of the talus with or without
      tibiocalcaneal fusion should be kept as a salvage procedure. We report a case of
      a farmer who sustained fracture of the talar neck. Both head and body fragments
      were completely extruded from the wound on the anterolateral aspect of the ankle.
      The patient was treated 18 hours postinjury. Thorough debridement of wound and
      bony fragments was done. Talus was reimplanted and fixation was performed with
      Kirschner wires. At 3-year follow-up, satisfactory functional outcome was noted
      with AOFAS (American Orthopaedic Foot and Ankle Society) score of 83 and MOXFQ
      (Manchester-Oxford Foot Questionnaire) scale score of 23. The purpose of
      presenting this case is to demonstrate the successful outcome of reimplantation
      of talus. LEVEL OF EVIDENCE: Therapeutic, Level IV: Case study.

PMID- 24686909
TI  - Biomechanical evaluation of a knotless barbed suture repair in a human Achilles
      tendon rupture model.
AB  - BACKGROUND: Knotless barbed sutures are seeing more common use in wound closures
      and small tendon repairs. The purpose of this study was to evaluate the strength
      and resistance to gap formation of these sutures in larger tendons, such as the
      Achilles, compared with conventional repair. METHODS: Six matched pairs of fresh
      frozen human cadaver Achilles tendons were transected to simulate a rupture. Six
      tendons were repaired using a double Bunnell over-the-top technique with
      Fiberwire, and the matched pairs were repaired using a double Bunnell knotless
      technique with barbed suture. The tendons were tested to failure and stiffness,
      peak failure load, percentage elongation, load at initial gap and load at 5-mm
      gap (clinical failure) were compared. RESULTS: The mean peak failure load for the
      Fiberwire group (459 N) was significantly higher (P = .029) compared with the
      barbed suture group (184 N). Percentage elongation at peak load was significantly
      lower in the barbed suture group (P = .014), as was percentage elongation at
      initial gapping (P = .007) and percent elongation at 5 mm of gapping (P = .004).
      CONCLUSION: While the knotless barbed suture is attractive for its design and
      resistance to gap formation, low failure loads compared with conventional suture
      are concerning for large tendon repairs. LEVELS OF EVIDENCE: Therapeutic, Level
      IV: Bench testing.

PMID- 24686910
TI  - Macrodystrophia lipomatosa of a fifth digit: a case report.
AB  - Macrodystrophia lipomatosa (MDL) is a rare, nonhereditary, congenital
      malformation that primarily affects the proliferation of mesenchymal structures.
      It presents with localized macrodactyly of one or more digits. The characteristic
      pathology is associated with hypertrophic fibroadipose tissues, more so to the
      plantar aspect of the foot. This condition can pose a threat to vascular supply,
      innervation, and even joint function. We present a single case of a 4-year-old
      male patient who presented with progressive enlargement of a unilateral left
      fifth digit since birth. The patient became increasingly symptomatic. Amputation
      was the selected treatment, and on pathological review of the specimen, the
      diagnosis of MDL was confirmed. The patient is approximately 1 year postoperative
      and has recovered uneventfully with an improved quality of life. The purpose of
      this article is to raise awareness of this condition with an emphasis on
      diagnosis through ancillary imaging results. LEVELS OF EVIDENCE: Therapeutic,
      Level IV: Case report.

PMID- 24686911
TI  - Acquisition and maintenance of scripts in aphasia: a comparison of two cuing
      conditions.
AB  - PURPOSE: This study was designed to compare acquisition and maintenance of
      scripts under two conditions: high cue, which provided numerous multimodality
      cues designed to minimize errors, and low cue, which provided minimal cues.
      METHOD: In a randomized controlled crossover study, eight individuals with
      chronic aphasia received intensive computer-based script training under two cuing
      conditions. Each condition lasted 3 weeks, with a 3-week washout period. Trained
      and untrained scripts were probed for accuracy and rate at baseline, during
      treatment, immediately posttreatment, and at 3 and 6 weeks posttreatment.
      Significance testing was conducted on gain scores, and effect sizes were
      calculated. RESULTS: Training resulted in significant gains in script acquisition
      with maintenance of skills at 3 and 6 weeks posttreatment. Differences between
      cuing conditions were not significant. When severity of aphasia was considered,
      there also were no significant differences between conditions, although magnitude
      of change was greater in the high-cue condition versus the low-cue condition for
      those with more severe aphasia. CONCLUSIONS: Both cuing conditions were effective
      in acquisition and maintenance of scripts. The high-cue condition may be
      advantageous for those with more severe aphasia. Findings support the clinical
      use of script training and the importance of considering aphasia severity.

PMID- 24686912
TI  - Differences in the performance of children with specific language impairment and
      their typically developing peers on nonverbal cognitive tests: a meta-analysis.
AB  - PURPOSE: This study used meta-analysis to investigate the difference in nonverbal
      cognitive test performance of children with specific language impairment (SLI)
      and their typically developing (TD) peers. METHOD: The meta-analysis included
      studies (a) that were published between 1995 and 2012 of children with SLI who
      were age matched (and not nonverbal cognitive matched) to TD peers and given a
      norm-referenced nonverbal cognitive test and (b) that reported sufficient data
      for an effect size analysis. Multilevel modeling was used to examine the
      performance of children with SLI relative to their typically developing, age
      matched peers on nonverbal IQ tests. RESULTS: Across 138 samples from 131
      studies, on average children with SLI scored 0.69 standard deviations below their
      TD peers on nonverbal cognitive tests after adjusting for the differences in the
      tests used, the low-boundary cutoff scores, the age of the participants, and
      whether studies matched the two groups on socioeconomic status. DISCUSSION: The
      lower performance of children with SLI relative to TD children on nonverbal IQ
      tests has theoretical implications for the characterization of SLI and clinical
      and political implications regarding how nonverbal cognitive tests are used and
      interpreted for children with this disorder.

PMID- 24686913
TI  - A novel papillomavirus in Adelie penguin (Pygoscelis adeliae) faeces sampled at
      the Cape Crozier colony, Antarctica.
AB  - Papillomaviruses are epitheliotropic viruses that have circular dsDNA genomes
      encapsidated in non-enveloped virions. They have been found to infect a variety
      of mammals, reptiles and birds, but so far they have not been found in
      amphibians. Using a next-generation sequencing de novo assembly contig-informed
      recovery, we cloned and Sanger sequenced the complete genome of a novel
      papillomavirus from the faecal matter of Adelie penguins (Pygoscelis adeliae)
      nesting on Ross Island, Antarctica. The genome had all the usual features of a
      papillomavirus and an E9 ORF encoding a protein of unknown function that is found
      in all avian papillomaviruses to date. This novel papillomavirus genome shared
      ~60 % pairwise identity with the genomes of the other three known avian
      papillomaviruses: Fringilla coelebs papillomavirus 1 (FcPV1), Francolinus
      leucoscepus papillomavirus 1 (FlPV1) and Psittacus erithacus papillomavirus 1.
      Pairwise identity analysis and phylogenetic analysis of the major capsid protein
      gene clearly indicated that it represents a novel species, which we named
      Pygoscelis adeliae papillomavirus 1 (PaCV1). No evidence of recombination was
      detected in the genome of PaCV1, but we did detect a recombinant region (119 nt)
      in the E6 gene of FlPV1 with the recombinant region being derived from ancestral
      FcPV1-like sequences. Previously only paramyxoviruses, orthomyxoviruses and avian
      pox viruses have been genetically identified in penguins; however, the majority
      of penguin viral identifications have been based on serology or histology. This
      is the first report, to our knowledge, of a papillomavirus associated with a
      penguin species.

PMID- 24686914
TI  - Effect of posttraumatic stress on study time in a task measuring four component
      processes underlying text-level reading.
AB  - PURPOSE: To investigate the effect of combat-related posttraumatic stress
      disorder (PTSD) on 4 components underlying text-level reading comprehension.
      METHOD: A group of 17 veterans with PTSD and 17 matched control participants took
      part. An experimental task required participants to read and study 3-sentence
      paragraphs describing semantic features associated with real and unreal objects.
      Each paragraph was followed by true-false statements that assessed knowledge
      access, text memory, inference, and integration. RESULTS: The results revealed
      that the PTSD group took significantly longer than the control group to study the
      paragraphs. Although there was no group difference in test statement accuracy,
      the PTSD group also took significantly longer to respond to the test statements.
      CONCLUSIONS: Overall, the results provide evidence for the control theory of
      attention but suggest that more direct measures of task-irrelevant processing
      during text-level reading are needed. More important, the results begin to lay a
      foundation for developing not only diagnostic but also intervention strategies.

PMID- 24686916
TI  - In vivo SiRNA transfection and gene knockdown in spinal cord via rapid
      noninvasive lumbar intrathecal injections in mice.
AB  - This report describes a step-by-step guide to the technique of acute intrathecal
      needle injections in a noninvasive manner, i.e. independent of catheter
      implantation. The technical limitation of this surgical technique lies in the
      finesse of the hands. The injection is rapid, especially for a trained
      experimenter, and since tissue disruption with this technique is minimal,
      repeated injections are possible; moreover immune reaction to foreign tools (e.g.
      catheter) does not occur, thereby giving a better and more specific read out of
      spinal cord modulation. Since the application of the substance is largely limited
      to the target region of the spinal cord, drugs do not need to be applied in large
      dosages, and more importantly unwanted effects on other tissue, as observed with
      a systemic delivery, could be circumvented(1,2). Moreover, we combine this
      technique with in vivo transfection of nucleic acid with the help of
      polyethylenimine (PEI) reagent(3), which provides tremendous versatility for
      studying spinal functions via delivery of pharmacological agents as well as gene,
      RNA, and protein modulators. 

PMID- 24686915
TI  - Development and preliminary evaluation of a pediatric Spanish-English speech
      perception task.
AB  - PURPOSE: The purpose of this study was to develop a task to evaluate children's
      English and Spanish speech perception abilities in either noise or competing
      speech maskers. METHOD: Eight bilingual Spanish-English and 8 age-matched
      monolingual English children (ages 4.9-16.4 years) were tested. A forced-choice,
      picture-pointing paradigm was selected for adaptively estimating masked speech
      reception thresholds. Speech stimuli were spoken by simultaneous bilingual
      Spanish-English talkers. The target stimuli were 30 disyllabic English and
      Spanish words, familiar to 5-year-olds and easily illustrated. Competing stimuli
      included either 2-talker English or 2-talker Spanish speech (corresponding to
      target language) and spectrally matched noise. RESULTS: For both groups of
      children, regardless of test language, performance was significantly worse for
      the 2-talker than for the noise masker condition. No difference in performance
      was found between bilingual and monolingual children. Bilingual children
      performed significantly better in English than in Spanish in competing speech.
      For all listening conditions, performance improved with increasing age.
      CONCLUSIONS: Results indicated that the stimuli and task were appropriate for
      speech recognition testing in both languages, providing a more conventional
      measure of speech-in-noise perception as well as a measure of complex listening.
      Further research is needed to determine performance for Spanish-dominant
      listeners and to evaluate the feasibility of implementation into routine clinical
      use.

PMID- 24686917
TI  - A prospective and nationwide study investigating endophthalmitis following pars
      plana vitrectomy: clinical presentation, microbiology, management and outcome.
AB  - BACKGROUND/AIMS: This is the first prospective and nationwide study aiming to
      provide epidemiological data relating to presentation, microbiology, management
      and outcome of endophthalmitis following vitrectomy. METHODS: Two years of
      prospective and nationwide surveillance for cases of presumed infectious
      endophthalmitis within 6 weeks of pars plana vitrectomy was completed. The study
      obtained case reports via the established British Ophthalmological Surveillance
      Unit (BOSU) system. RESULTS: Thirty-seven cases were reported and 28 met the
      diagnostic criteria for presumed infectious endophthalmitis following vitrectomy.
      Mean age was 61 years and 67% were male. Nineteen cases were 23/25 gauge and 9
      cases were 20 gauge. Mean time from surgery to endophthalmitis was 5 days.
      Blurred vision (85.2%), pain (77.8%) and a hypopyon (77.8%) were the commonest
      presenting symptoms and signs. Seventeen cases (60.7%) had a positive culture.
      Culture-positive endophthalmitis, relative to culture-negative endophthalmitis,
      was no different with respect to time to presentation, symptoms, signs or
      outcome. Outcome was poor, with 29.6% of eyes being eviscerated or having no
      perception of light or perception of light. CONCLUSIONS: This study helps
      surgeons promptly identify cases of endophthalmitis following vitrectomy and
      informs them about the various management options currently used and the likely
      outcome of this devastating complication.

PMID- 24686919
TI  - Keynes, Newton and the Royal Society: the events of 1942 and 1943.
AB  - Most discussions of John Maynard Keynes's activities in connection with Newton
      are restricted to the sale in 1936 at Sotheby's of Newton's Portsmouth Papers and
      to Keynes's 1946 essay 'Newton, the Man'. This paper provides a history of
      Keynes's Newton-related work in the interim, highlighting especially the events
      of 1942 and 1943, which were particularly relevant to the Royal Society's role in
      the domestic and international promotion of Newton's legacy. During this period,
      Keynes lectured twice on Newton, leaving notes that would later be read by his
      brother Geoffrey in the famous commemoration of the Newton tercentenary in 1946.
      In 1943 Keynes assisted the Royal Society in its recognition of the Soviet
      celebrations and in the acquisition and preservation of more of the Newton
      library. In each instance Keynes took the opportunity to promote his
      interpretation of Newton as 'the last of the magicians': a scientist who had one
      foot in the pre-modern world and whose approach to understanding the world was as
      much intuitive as it was methodical.

PMID- 24686918
TI  - Who uses physician-rating websites? Differences in sociodemographic variables,
      psychographic variables, and health status of users and nonusers of physician
      rating websites.
AB  - BACKGROUND: The number of physician-rating websites (PRWs) is rising rapidly, but
      usage is still poor. So far, there has been little discussion about what kind of
      variables influence usage of PRWs. OBJECTIVE: We focused on sociodemographic
      variables, psychographic variables, and health status of PRW users and nonusers.
      METHODS: An online survey of 1006 randomly selected German patients was conducted
      in September 2012. We analyzed the patients' knowledge and use of online PRWs. We
      also analyzed the impact of sociodemographic variables (gender, age, and
      education), psychographic variables (eg, feelings toward the Internet, digital
      literacy), and health status on use or nonuse as well as the judgment of and
      behavior intentions toward PRWs. The survey instrument was based on existing
      literature and was guided by several research questions. RESULTS: A total of
      29.3% (289/986) of the sample knew of a PRW and 26.1% (257/986) had already used
      a PRW. Younger people were more prone than older ones to use PRWs (t967=2.27,
      P=.02). Women used them more than men (chi(2) 1=9.4, P=.002), the more highly
      educated more than less educated people (chi(2) 4=19.7, P=.001), and people with
      chronic diseases more than people without (chi(2) 1=5.6, P=.02). No differences
      were found between users and nonusers in their daily private Internet use and in
      their use of the Internet for health-related information. Users had more positive
      feelings about the Internet and other Web-based applications in general
      (t489=3.07, P=.002) than nonusers, and they had higher digital literacy
      (t520=4.20, P<.001). Users ascribed higher usefulness to PRWs than nonusers
      (t612=11.61, P<.001) and users trusted information on PRWs to a greater degree
      than nonusers (t559=11.48, P<.001). Users were also more likely to rate a
      physician on a PRW in the future (t367=7.63, P<.001) and to use a PRW in the
      future (t619=15.01, P<.001). The results of 2 binary logistic regression analyses
      demonstrated that sociodemographic variables (gender, age, education) and health
      status alone did not predict whether persons were prone to use PRWs or not.
      Adding psychographic variables and information-seeking behavior variables to the
      binary logistic regression analyses led to a satisfying fit of the model and
      revealed that higher education, poorer health status, higher digital literacy (at
      the 10% level of significance), lower importance of family and pharmacist for
      health-related information, higher trust in information on PRWs, and higher
      appraisal of usefulness of PRWs served as significant predictors for usage of
      PRWs. CONCLUSIONS: Sociodemographic variables alone do not sufficiently predict
      use or nonuse of PRWs; specific psychographic variables and health status need to
      be taken into account. The results can help designers of PRWs to better tailor
      their product to specific target groups, which may increase use of PRWs in the
      future.

PMID- 24686920
TI  - Role of 18f-fdg-pet/ct in assessment of pediatric Hodgkin's lymphoma.
AB  - AIM: To assess the prognostic role of interim 18FFDGPET/CT in pediatric patients
      with Hodgkin's lymphoma (PHL). METHODS: Prospective analysis of 254 Saudi
      patients with pathologically proven PHL, they underwent interim 18F-FDG-PET/CT
      after 2 cycles of ABVD with baseline study, analysis of interim 18F-FDG-PET/CT
      was done visually according to the Deauville score (5-point score) as well as
      semi-quantitative analysis using maximum standardized uptake value (SUVmax),
      average SUV (SUVmean2.5 and SUVmean40). The parameters were calculated as
      absolute values and as percentages of difference between the initial and the
      interim hottest residual lesion. Follow-up was done for period of 2.9 years
      (range, 0.9 to 5.2 years). clinical outcomes were obtained from medical records.
      RESULTS: two hundred and twenty out of 254 children showed PET-ve interim while
      34 were still PET+ve. Univariate analysis showed that the risk stratification,
      qualitative analysis of interim 18F-FDG-PET/CT were significant predictors for
      total actuarial survival (TAS) and disease free survival (DFS). Among the
      semiquantitative parameters, DeltaSUVmean2.5 has the highest hazard ratio. In
      multivariate analysis, the current study revealed that the three above factors
      were important prognostic factors that can predict TAS and DFS. However, visual
      assessment of interim PET canceled the prognostic impact of DeltaSUVmean2.5.
      CONCLUSION: visual assessment of early interim 18F-FDG-PET/CT after 2 cycles of
      ABVD in PHL showed a very significant role in prediction ofTAS and DFS.

PMID- 24686921
TI  - Fungal phenalenones: chemistry, biology, biosynthesis and phylogeny.
AB  - Covering up to the end of August 2013. Phenalenones are members of a unique class
      of natural polyketides exhibiting diverse biological potential. This is a
      comprehensive review of 72 phenalenones with diverse structural features
      originating from fungal sources. Their bioactive potential and structure
      elucidation are discussed along with a review of their biosynthetic pathways and
      the taxonomical relationship between the fungi producing these natural products.

PMID- 24686922
TI  - Children with a history of SLI show reduced sensitivity to audiovisual temporal
      asynchrony: an ERP study.
AB  - PURPOSE: The authors examined whether school-age children with a history of
      specific language impairment (H-SLI), their peers with typical development (TD),
      and adults differ in sensitivity to audiovisual temporal asynchrony and whether
      such difference stems from the sensory encoding of audiovisual information.
      METHOD: Fifteen H-SLI children, 15 TD children, and 15 adults judged whether a
      flashed explosion-shaped figure and a 2-kHz pure tone occurred simultaneously.
      The stimuli were presented at 0-, 100-, 200-, 300-, 400-, and 500-ms temporal
      offsets. This task was combined with EEG recordings. RESULTS: H-SLI children were
      profoundly less sensitive to temporal separations between auditory and visual
      modalities compared with their TD peers. Those H-SLI children who performed
      better at simultaneity judgment also had higher language aptitude. TD children
      were less accurate than adults, revealing a remarkably prolonged developmental
      course of the audiovisual temporal discrimination. Analysis of early event
      related potential components suggested that poor sensory encoding was not a key
      factor in H-SLI children's reduced sensitivity to audiovisual asynchrony.
      CONCLUSIONS: Audiovisual temporal discrimination is impaired in H-SLI children
      and is still immature during mid-childhood in TD children. The present findings
      highlight the need for further evaluation of the role of atypical audiovisual
      processing in the development of SLI.

PMID- 24686923
TI  - Water-soluble porphyrin nanospheres: enhanced photo-physical properties achieved
      via cyclodextrin driven double self-inclusion.
AB  - We describe a method to construct water-soluble porphyrinic nanospheres with
      enhanced photo-physical properties as a result of precluding (via intra-molecular
      host-guest interactions) the individual porphyrins units from aromatic-aromatic
      stacking. 

PMID- 24686924
TI  - Effect of hospitalist workload on the quality and efficiency of care.
AB  - IMPORTANCE: Hospitalist physicians face increasing pressure to maximize
      productivity, which may undermine the efficiency and quality of care. OBJECTIVE:
      To determine the association between hospitalist workload and the efficiency and
      quality of inpatient care. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
      retrospective cohort study of 20,241 admissions of inpatients cared for by a
      private hospitalist group at a large academic community hospital system between
      February 1, 2008, and January 31, 2011. EXPOSURES: Daily hospitalist workload as
      measured by relative value units and patient encounters from the hospitalist
      billing records. MAIN OUTCOMES AND MEASURES: The main outcomes were length of
      stay (LOS), cost, rapid response team activation, in-hospital mortality, patient
      satisfaction, and 30-day readmission rates. Key covariates included hospital
      occupancy and patient-level characteristics. RESULTS: The LOS increased as
      workload increased, particularly at lower hospital occupancy. For hospital
      occupancies less than 75%, LOS increased from 5.5 to 7.5 days as workload
      increased. For occupancies of 75% to 85%, LOS increased exponentially above a
      daily relative value unit of approximately 25 and a census value of approximately
      15. At high occupancy (>85%), LOS was J-shaped, with significant increases at
      higher ranges of workload. After controlling for LOS, cost increased by $111 for
      each 1-unit increase in relative value unit and $205 for each 1-unit increase in
      census across the range of values. Changes in workload were not associated with
      the remaining outcomes. CONCLUSIONS AND RELEVANCE: Increasing hospitalist
      workload is associated with clinically meaningful increases in LOS and cost.
      Although our findings should be validated in different clinical settings, our
      results suggest the need for methods to mitigate the potential negative effects
      of increased hospitalist workload on the efficiency and cost of care.

PMID- 24686925
TI  - Preliminary results on the influence of engineered artificial mucus layer on
      phonation.
AB  - PURPOSE Previous studies have confirmed the influence of dehydration and an
      altered mucus (e.g., due to pathologies) on phonation. However, the underlying
      reasons for these influences are not fully understood. This study was a
      preliminary inquiry into the influences of mucus architecture and concentration
      on vocal fold oscillation. METHOD Two excised human larynges were investigated in
      an in vitro setup. The oscillations of the vocal folds at various airflow volume
      rates were recorded through the use of high-speed imaging. Engineered mucus
      containing polymers (interconnected polymers and linear polymers) was applied to
      the vocal folds. From the high-speed footage, glottal parameters were extracted
      through the use of objective methods and were compared to a gold standard
      (physiological saline solution). RESULTS Variations were found for all
      applications of mucus. Fundamental frequency dropped and the oscillatory behavior
      (speed quotient [SQ], closing quotient [CQ]) changed for both larynges. The 2
      applied mucus architectures displayed different effects on the larynges. The
      interconnected polymer displayed clear low-pass filter characteristics not found
      for the linear polymer. Increase of polymer concentration affected parameters to
      a certain point. CONCLUSION The data confirm results found in previous studies.
      Furthermore, the different effects-comparing architecture and concentration
      suggest that, in the future, synthetic mucus can be designed to improve
      phonation. 

PMID- 24686926
TI  - Effect of phonotactic probability and neighborhood density on word-learning
      configuration by preschoolers with typical development and specific language
      impairment.
AB  - PURPOSE: In this study, the authors assessed the effects of phonotactic
      probability and neighborhood density on word-learning configuration by
      preschoolers with specific language impairment (SLI) and typical language
      development (TD). METHOD: One hundred thirty-one children participated: 48 with
      SLI, 44 with TD matched on age and gender, and 39 with TD matched on vocabulary
      and gender. Referent identification and naming were assessed in a computer-based
      learning context. RESULTS: For referent identification, preschoolers with TD
      benefited from high phonotactic probability, and the younger group also benefited
      from low neighborhood density. In contrast, the SLI group benefited only from
      high neighborhood density. For naming, older preschoolers with TD benefited most
      from low-density words, younger preschoolers with TD benefited most from words
      with high phonotactic probability, and the SLI group showed no advantage.
      CONCLUSION: Phonotactic probability and neighborhood density had different
      effects on each group that may be related to children's ability to store well
      specified word forms and to the size of their extant lexicon. The authors argue
      that cross-study comparisons of word learning are needed; therefore, researchers
      should describe word, referent, and learner characteristics and the learning
      context and should situate their studies in a triggering -> configuration +
      engagement model of word learning.

PMID- 24686927
TI  - Numerical investigation of fluid flow in a chandler loop.
AB  - The Chandler loop is an artificial circulatory platform for in vitro hemodynamic
      experiments. In most experiments, the working fluid is subjected to a strain rate
      field via rotation of the Chandler loop, which, in turn, induces biochemical
      responses of the suspended cells. For low rotation rates, the strain rate field
      can be approximated using laminar flow in a straight tube. However, as the
      rotation rate increases, the effect of the tube curvature causes significant
      deviation from the laminar straight tube approximation. In this manuscript, we
      investigate the flow and associated strain rate field of an incompressible
      Newtonian fluid in a Chandler loop as a function of the governing nondimensional
      parameters. Analytical estimates of the strain rate from a perturbation solution
      for pressure driven steady flow in a curved tube suggest that the strain rate
      should increase with Dean number, which is proportional to the tangential
      velocity of the rotating tube, and the radius to radius of curvature ratio of the
      loop. Parametrically varying the rotation rate, tube geometry, and fill ratio of
      the loop show that strain rate can actually decrease with Dean number. We show
      that this is due to the nonlinear relationship between the tube rotation rate and
      height difference between the two menisci in the rotating tube, which provides
      the driving pressure gradient. An alternative Dean number is presented to
      naturally incorporate the fill ratio and collapse the numerical data. Using this
      modified Dean number, we propose an empirical formula for predicting the average
      fluid strain rate magnitude that is valid over a much wider parameter range than
      the more restrictive straight tube-based prediction.

PMID- 24686928
TI  - Inclusive fitness: 50 years on.

PMID- 24686930
TI  - Quantitative genetic versions of Hamilton's rule with empirical applications.
AB  - Hamilton's theory of inclusive fitness revolutionized our understanding of the
      evolution of social interactions. Surprisingly, an incorporation of Hamilton's
      perspective into the quantitative genetic theory of phenotypic evolution has been
      slow, despite the popularity of quantitative genetics in evolutionary studies.
      Here, we discuss several versions of Hamilton's rule for social evolution from a
      quantitative genetic perspective, emphasizing its utility in empirical
      applications. Although evolutionary quantitative genetics offers methods to
      measure each of the critical parameters of Hamilton's rule, empirical work has
      lagged behind theory. In particular, we lack studies of selection on altruistic
      traits in the wild. Fitness costs and benefits of altruism can be estimated using
      a simple extension of phenotypic selection analysis that incorporates the traits
      of social interactants. We also discuss the importance of considering the genetic
      influence of the social environment, or indirect genetic effects (IGEs), in the
      context of Hamilton's rule. Research in social evolution has generated an
      extensive body of empirical work focusing--with good reason--almost solely on
      relatedness. We argue that quantifying the roles of social and non-social
      components of selection and IGEs, in addition to relatedness, is now timely and
      should provide unique additional insights into social evolution.

PMID- 24686929
TI  - The genetical theory of social behaviour.
AB  - We survey the population genetic basis of social evolution, using a logically
      consistent set of arguments to cover a wide range of biological scenarios. We
      start by reconsidering Hamilton's (Hamilton 1964 J. Theoret. Biol. 7, 1-16
      (doi:10.1016/0022-5193(64)90038-4)) results for selection on a social trait under
      the assumptions of additive gene action, weak selection and constant environment
      and demography. This yields a prediction for the direction of allele frequency
      change in terms of phenotypic costs and benefits and genealogical concepts of
      relatedness, which holds for any frequency of the trait in the population, and
      provides the foundation for further developments and extensions. We then allow
      for any type of gene interaction within and between individuals, strong selection
      and fluctuating environments and demography, which may depend on the evolving
      trait itself. We reach three conclusions pertaining to selection on social
      behaviours under broad conditions. (i) Selection can be understood by focusing on
      a one-generation change in mean allele frequency, a computation which underpins
      the utility of reproductive value weights; (ii) in large populations under the
      assumptions of additive gene action and weak selection, this change is of
      constant sign for any allele frequency and is predicted by a phenotypic selection
      gradient; (iii) under the assumptions of trait substitution sequences, such
      phenotypic selection gradients suffice to characterize long-term multi
      dimensional stochastic evolution, with almost no knowledge about the genetic
      details underlying the coevolving traits. Having such simple results about the
      effect of selection regardless of population structure and type of social
      interactions can help to delineate the common features of distinct biological
      processes. Finally, we clarify some persistent divergences within social
      evolution theory, with respect to exactness, synergies, maximization, dynamic
      sufficiency and the role of genetic arguments. 

PMID- 24686931
TI  - Evolutionary dynamics of n-player games played by relatives.
AB  - One of the core concepts in social evolution theory is kin selection. Kin
      selection provides a perspective to understand how natural selection operates
      when genetically similar individuals are likely to interact. A family-structured
      population is an excellent example of this, where relatives are engaged in social
      interactions. Consequences of such social interactions are often described in
      game-theoretical frameworks, but there is a growing consensus that a naive
      inclusive fitness accounting with dyadic relatedness coefficients are of limited
      use when non-additive fitness effects are essential in those situations. Here, I
      provide a general framework to analyse multiplayer interactions among relatives.
      Two important results follow from my analysis. First, it is generally necessary
      to know the n-tuple genetic association of family members when n individuals are
      engaged in social interactions. However, as a second result, I found that, for a
      special class of games, we need only measures of lower-order genetic association
      to fully describe its evolutionary dynamics. I introduce the concept of degree of
      the game and show how this degree is related to the degree of genetic
      association. 

PMID- 24686933
TI  - Inclusive-fitness logic of cooperative breeding with benefits of natal
      philopatry.
AB  - In cooperatively breeding species, individuals help to raise offspring that are
      not their own. We use two inclusive-fitness models to study the advantage of this
      kind of helpful behaviour in social groups with high reproductive skew. Our first
      model does not allow for competition among relatives to occur but our second
      model does. Specifically, our second model assumes a competitive hierarchy among
      nest-mates, with non-breeding helpers ranked higher than their newborn siblings.
      For each model, we obtain an expression for the change in inclusive fitness
      experienced by a helpful individual in a selfish population. The prediction
      suggested by each expression is confirmed with computer simulation. When model
      predictions are compared to one another, we find that helping emerges under a
      broader range of conditions in the second model. Although competition among kin
      occurs in our second model, we conclude that the life-history features associated
      with this competition also act to promote the evolutionary transition from
      solitary to cooperative breeding. 

PMID- 24686932
TI  - Hamilton's inclusive fitness in finite-structured populations.
AB  - Hamilton's formulation of inclusive fitness has been with us for 50 years. During
      the first 20 of those years attention was largely focused on the evolutionary
      trajectories of different behaviours, but over the past 20 years interest has
      been growing in the effect of population structure on the evolution of behaviour
      and that is our focus here. We discuss the evolutionary journey of the inclusive
      fitness effect over this epoch, nurtured as it was in an essentially homogeneous
      environment (that of 'transitive' structures) having to adapt in different ways
      to meet the expectations of heterogeneous structures. We pay particular attention
      to the way in which the theory has managed to adapt the original constructs of
      relatedness and reproductive value to provide a formulation of inclusive fitness
      that captures a precise measure of allele-frequency change in finite-structured
      populations. 

PMID- 24686934
TI  - Hamilton's rule and the causes of social evolution.
AB  - Hamilton's rule is a central theorem of inclusive fitness (kin selection) theory
      and predicts that social behaviour evolves under specific combinations of
      relatedness, benefit and cost. This review provides evidence for Hamilton's rule
      by presenting novel syntheses of results from two kinds of study in diverse taxa,
      including cooperatively breeding birds and mammals and eusocial insects. These
      are, first, studies that empirically parametrize Hamilton's rule in natural
      populations and, second, comparative phylogenetic analyses of the genetic, life
      history and ecological correlates of sociality. Studies parametrizing Hamilton's
      rule are not rare and demonstrate quantitatively that (i) altruism (net loss of
      direct fitness) occurs even when sociality is facultative, (ii) in most cases,
      altruism is under positive selection via indirect fitness benefits that exceed
      direct fitness costs and (iii) social behaviour commonly generates indirect
      benefits by enhancing the productivity or survivorship of kin. Comparative
      phylogenetic analyses show that cooperative breeding and eusociality are promoted
      by (i) high relatedness and monogamy and, potentially, by (ii) life-history
      factors facilitating family structure and high benefits of helping and (iii)
      ecological factors generating low costs of social behaviour. Overall, the focal
      studies strongly confirm the predictions of Hamilton's rule regarding conditions
      for social evolution and their causes. 

PMID- 24686935
TI  - Genetic conflict, kin and the origins of novel genetic systems.
AB  - Genetic conflict may have played an important role in the evolution of novel
      genetic systems. The ancestral system of eumendelian genetics is highly
      symmetrical. Those derived from it (e.g. thelytokous parthenogenesis,
      haplodiploidy and parent-specific allele expression) are more asymmetrical in the
      genetic role played by maternal versus paternal alleles. These asymmetries may
      have arisen from maternal-paternal genetic conflict, or cytonuclear conflict, or
      from an interaction between them. Asymmetric genetic systems are much more common
      in terrestrial and freshwater taxa than in marine taxa. We suggest three reasons
      for this, based on the relative inhospitability of terrestrial environments to
      three types of organism: (i) pathogens-departure from the marine realm meant
      escape from many pathogens and parasites, reducing the need for sexual
      reproduction; (ii) symbionts-symbionts are no more important in the terrestrial
      realm than the marine realm but are more likely to be obligately intracellular
      and vertically transmitted, making them more likely to disrupt their host's
      genetic systems; (iii) Gametes and embryos-because neither gametes nor embryos
      can be shed into air as easily as into seawater, the mother's body is a more
      important environment for both types of organisms in the terrestrial realm than
      in the marine realm. This environment of asymmetric kinship (with neighbours more
      closely related by maternal alleles than by paternal alleles) may have helped to
      drive asymmetries in expression and transmission. 

PMID- 24686936
TI  - War and peace: social interactions in infections.
AB  - One of the most striking facts about parasites and microbial pathogens that has
      emerged in the fields of social evolution and disease ecology in the past few
      decades is that these simple organisms have complex social lives, indulging in a
      variety of cooperative, communicative and coordinated behaviours. These organisms
      have provided elegant experimental tests of the importance of relatedness, kin
      discrimination, cooperation and competition, in driving the evolution of social
      strategies. Here, we briefly review the social behaviours of parasites and
      microbial pathogens, including their contributions to virulence, and outline how
      inclusive fitness theory has helped to explain their evolution. We then take a
      mechanistically inspired 'bottom-up' approach, discussing how key aspects of the
      ways in which parasites and pathogens exploit hosts, namely public goods, mobile
      elements, phenotypic plasticity, spatial structure and multi-species
      interactions, contribute to the emergent properties of virulence and
      transmission. We argue that unravelling the complexities of within-host ecology
      is interesting in its own right, and also needs to be better incorporated into
      theoretical evolution studies if social behaviours are to be understood and used
      to control the spread and severity of infectious diseases. 

PMID- 24686939
TI  - How Darwinian is cultural evolution?
AB  - Darwin-inspired population thinking suggests approaching culture as a population
      of items of different types, whose relative frequencies may change over time.
      Three nested subtypes of populational models can be distinguished: evolutionary,
      selectional and replicative. Substantial progress has been made in the study of
      cultural evolution by modelling it within the selectional frame. This progress
      has involved idealizing away from phenomena that may be critical to an adequate
      understanding of culture and cultural evolution, particularly the constructive
      aspect of the mechanisms of cultural transmission. Taking these aspects into
      account, we describe cultural evolution in terms of cultural attraction, which is
      populational and evolutionary, but only selectional under certain circumstances.
      As such, in order to model cultural evolution, we must not simply adjust existing
      replicative or selectional models but we should rather generalize them, so that,
      just as replicator-based selection is one form that Darwinian selection can take,
      selection itself is one of several different forms that attraction can take. We
      present an elementary formalization of the idea of cultural attraction. 

PMID- 24686937
TI  - First principles of Hamiltonian medicine.
AB  - We introduce the field of Hamiltonian medicine, which centres on the roles of
      genetic relatedness in human health and disease. Hamiltonian medicine represents
      the application of basic social-evolution theory, for interactions involving
      kinship, to core issues in medicine such as pathogens, cancer, optimal growth and
      mental illness. It encompasses three domains, which involve conflict and
      cooperation between: (i) microbes or cancer cells, within humans, (ii) genes
      expressed in humans, (iii) human individuals. A set of six core principles, based
      on these domains and their interfaces, serves to conceptually organize the field,
      and contextualize illustrative examples. The primary usefulness of Hamiltonian
      medicine is that, like Darwinian medicine more generally, it provides novel
      insights into what data will be productive to collect, to address important
      clinical and public health problems. Our synthesis of this nascent field is
      intended predominantly for evolutionary and behavioural biologists who aspire to
      address questions directly relevant to human health and disease. 

PMID- 24686940
TI  - Joint phenotypes, evolutionary conflict and the fundamental theorem of natural
      selection.
AB  - Multiple organisms can sometimes affect a common phenotype. For example, the
      portion of a leaf eaten by an insect is a joint phenotype of the plant and insect
      and the amount of food obtained by an offspring can be a joint trait with its
      mother. Here, I describe the evolution of joint phenotypes in quantitative
      genetic terms. A joint phenotype for multiple species evolves as the sum of
      additive genetic variances in each species, weighted by the selection on each
      species. Selective conflict between the interactants occurs when selection takes
      opposite signs on the joint phenotype. The mean fitness of a population changes
      not just through its own genetic variance but also through the genetic variance
      for its fitness that resides in other species, an update of Fisher's fundamental
      theorem of natural selection. Some similar results, using inclusive fitness,
      apply to within-species interactions. The models provide a framework for
      understanding evolutionary conflicts at all levels. 

PMID- 24686938
TI  - Inclusive fitness in agriculture.
AB  - Trade-offs between individual fitness and the collective performance of crop and
      below-ground symbiont communities are common in agriculture. Plant
      competitiveness for light and soil resources is key to individual fitness, but
      higher investments in stems and roots by a plant community to compete for those
      resources ultimately reduce crop yields. Similarly, rhizobia and mycorrhizal
      fungi may increase their individual fitness by diverting resources to their own
      reproduction, even if they could have benefited collectively by providing their
      shared crop host with more nitrogen and phosphorus, respectively. Past selection
      for inclusive fitness (benefits to others, weighted by their relatedness) is
      unlikely to have favoured community performance over individual fitness. The
      limited evidence for kin recognition in plants and microbes changes this
      conclusion only slightly. We therefore argue that there is still ample
      opportunity for human-imposed selection to improve cooperation among crop plants
      and their symbionts so that they use limited resources more efficiently. This
      evolutionarily informed approach will require a better understanding of how
      interactions among crops, and interactions with their symbionts, affected their
      inclusive fitness in the past and what that implies for current interactions. 

PMID- 24686941
TI  - Helping in cooperatively breeding long-tailed tits: a test of Hamilton's rule.
AB  - Inclusive fitness theory provides the conceptual framework for our current
      understanding of social evolution, and empirical studies suggest that kin
      selection is a critical process in the evolution of animal sociality. A key
      prediction of inclusive fitness theory is that altruistic behaviour evolves when
      the costs incurred by an altruist (c) are outweighed by the benefit to the
      recipient (b), weighted by the relatedness of altruist to recipient (r), i.e.
      Hamilton's rule rb > c. Despite its central importance in social evolution
      theory, there have been relatively few empirical tests of Hamilton's rule, and
      hardly any among cooperatively breeding vertebrates, leading some authors to
      question its utility. Here, we use data from a long-term study of cooperatively
      breeding long-tailed tits Aegithalos caudatus to examine whether helping
      behaviour satisfies Hamilton's condition for the evolution of altruism. We show
      that helpers are altruistic because they incur survival costs through the
      provision of alloparental care for offspring. However, they also accrue
      substantial benefits through increased survival of related breeders and
      offspring, and despite the low average relatedness of helpers to recipients,
      these benefits of helping outweigh the costs incurred. We conclude that
      Hamilton's rule for the evolution of altruistic helping behaviour is satisfied in
      this species. 

PMID- 24686942
TI  - A theoretical muddle of the conditional strategy: a comment on Neff and Svensson.

PMID- 24686944
TI  - Interventional cardiology. DAPT use and DES type.

PMID- 24686945
TI  - Vascular disease. Disparities in treatment and mortality from ruptured AAA
      between England and the USA.

PMID- 24686946
TI  - Pathophysiology and epidemiology of peripartum cardiomyopathy.
AB  - Cardiovascular diseases are a major cause of complications in pregnancy
      worldwide, and the number of patients who develop cardiac problems during
      pregnancy is increasing. Peripartum cardiomyopathy (PPCM) is a potentially life
      threatening heart disease that emerges towards the end of pregnancy or in the
      first months postpartum, in previously healthy women. Symptoms and signs of PPCM
      are similar to those in patients with idiopathic dilated cardiomyopathy. The
      incidence varies geographically, most likely because of socioeconomic and genetic
      factors. The syndrome is associated with a high morbidity and mortality, and
      diagnosis is often delayed. Various mechanisms have been investigated, including
      the hypothesis that unbalanced peripartum or postpartum oxidative stress triggers
      the proteolytic cleavage of the nursing hormone prolactin into a potent
      antiangiogenic, proapoptotic, and proinflammatory 16 kDa fragment. This theory
      provides the basis for the discovery of disease-specific biomarkers and promising
      novel therapeutic targets. In this Review, we describe the latest understanding
      of the epidemiology, pathophysiology, and novel treatment strategies for patients
      with PPCM.

PMID- 24686948
TI  - Sera from remitting and secondary progressive multiple sclerosis patients disrupt
      the blood-brain barrier.
AB  - BACKGROUND: Pathological destruction of blood-brain barrier (BBB) has been
      thought to be the initial key event in the process of developing multiple
      sclerosis (MS). The purpose of the present study was to clarify the possible
      molecular mechanisms responsible for the malfunction of BBB by sera from relapse
      remitting MS (RRMS) and secondary progressive MS (SPMS) patients. METHODS: We
      evaluated the effects of sera from the patients in the relapse phase of RRMS
      (RRMS-R), stable phase of RRMS (RRMS-S) and SPMS on the expression of tight
      junction proteins and vascular cell adhesion protein-1 (VCAM-1), and on the
      transendothelial electrical resistance (TEER) in human brain microvascular
      endothelial cells (BMECs). RESULTS: Sera from the RRMS-R or SPMS patients
      decreased the claudin-5 protein expression and the TEER in BMECs. In RRMS-R, this
      effect was restored after adding an MMP inhibitor, and the MMP-2/9 secretion by
      BMECs was significantly increased after the application of patients' sera. In
      SPMS, the immunoglobulin G (IgG) purified from patients' sera also decreased the
      claudin-5 protein expression and the TEER in BMECs. The sera and purified IgG
      from all MS patients increased the VCAM-1 protein expression in BMECs.
      CONCLUSIONS: The up-regulation of autocrine MMP-2/9 by BMECs after exposure to
      sera from RRMS-R patients or the autoantibodies against BMECs from SPMS patients
      can compromise the BBB. Both RRMS-S and SPMS sera increased the VCAM-1 expression
      in the BBB, thus indicating that targeting the VCAM-1 in the BBB could represent
      a possible therapeutic strategy for even the stable phase of MS and SPMS.

PMID- 24686949
TI  - Growth of millimeter-size single crystal graphene on Cu foils by circumfluence
      chemical vapor deposition.
AB  - A simply and reproducible way is proposed to significantly suppress the
      nucleation density of graphene on the copper foil during the chemical vapor
      deposition process. By inserting a copper foil into a tube with one close end,
      the nucleation density on the copper foils can be reduced by more than five
      orders of magnitude and an ultra-low nucleation density of ~10 nucleus/cm(2) has
      been achieved. The structural analyses demonstrate that single crystal monolayer
      graphene with a lateral size of 1.9 mm can be grown on the copper foils under the
      optimized growth condition. The electrical transport studies show that the
      mobility of such single crystal graphene is around 2400 cm(2)/Vs.

PMID- 24686950
TI  - Examining correlates of game-to-game variation in volleyball players' achievement
      goal pursuit and underlying autonomous and controlling reasons.
AB  - In the current study we aimed to examine the antecedents and outcomes associated
      with the variability in competitive volleyball players' (N = 67; Mage = 19.45; SD
      = 5.13) situational achievement goal pursuit and its underlying autonomous and
      controlling reasons. Players were followed during six consecutive games and data
      were analyzed through multilevel modeling. Players' dominant contextual goal
      pursuit reported at the onset of the study related to their situational (i.e.,
      game-specific) goal pursuit. Further, variation in game-to-game mastery-approach
      goal pursuit, as compared with the pursuit of other achievement goals, related to
      variation in prosocial behavior. Finally, autonomous reasons underlying
      situational mastery-approach goal pursuit related positively to games-specific
      prosocial behavior, enjoyment, and performance satisfaction. The discussion
      emphasizes the necessity to study players' game-to-game motivational dynamics and
      the reasons underlying players' achievement goal pursuit. 

PMID- 24686951
TI  - Sources of self-efficacy and coach/instructor behaviors underlying relation
      inferred self-efficacy (RISE) in recreational youth sport.
AB  - Interpersonal feedback from coaches may be instrumental in the formation of
      children's self-efficacy to learn or perform sport skills. We report on two
      studies that explored perceived sources of self-efficacy and relation-inferred
      self-efficacy (RISE) in one-on-one interviews with sport camp participants (N =
      61; ages 7-12) and focus groups with recreational league participants (N = 28;
      ages 8-12). Participants' responses indicated that prior experiences and socially
      constructed interactions contributed to the development of self-efficacy and RISE
      beliefs. Results support Bandura's (1997) theorizing that self-efficacy is
      developed through processing of experiential feedback as well as Lent and Lopez's
      (2002) tripartite theory proposing interpersonal feedback from influential others
      contributes to children's RISE and self-efficacy. 

PMID- 24686952
TI  - Habits predict physical activity on days when intentions are weak.
AB  - Physical activity is regulated by controlled processes, such as intentions, and
      automatic processes, such as habits. Intentions relate to physical activity more
      strongly for people with weak habits than for people with strong habits, but
      people's intentions vary day by day. Physical activity may be regulated by habits
      unless daily physical activity intentions are strong. University students (N =
      128) self-reported their physical activity habit strength and subsequently self
      reported daily physical activity intentions and wore an accelerometer for 14
      days. On days when people had intentions that were weaker than typical for them,
      habit strength was positively related to physical activity, but on days when
      people had typical or stronger intentions than was typical for them, habit
      strength was unrelated to daily physical activity. Efforts to promote physical
      activity may need to account for habits and the dynamics of intentions. 

PMID- 24686953
TI  - Daily satisfaction with life is regulated by both physical activity and sedentary
      behavior.
AB  - Recent research revealed that on days when college students engage in more
      physical activity than is typical for them, they also experience greater
      satisfaction with life (SWL). That work relied on self-reported physical activity
      and did not differentiate between low levels of physical activity and sedentary
      behavior. This study was designed to (1) determine if the association between
      self-reported physical activity and SWL would exist when physical activity was
      monitored objectively and (2) examine the between- and within-person associations
      among physical activity, sedentary behavior, and SWL. During a 14-day ecological
      momentary assessment study, college students (N = 128) wore an accelerometer to
      objectively measure physical activity and sedentary behavior, and they self
      reported their physical activity, sedentary behavior, and SWL at the end of each
      day. Physical activity and sedentary behavior had additive, within-person
      associations with SWL across self-reported and objective-measures of behavior.
      Strategies to promote daily well-being should encourage college students to
      incorporate greater amounts of physical activity as well as limit their sedentary
      behavior. 

PMID- 24686954
TI  - Testing measurement invariance across Spanish and English versions of the
      physical self-description questionnaire: an application of exploratory structural
      equation modeling.
AB  - Test of measurement invariance across translated versions of questionnaires is a
      critical prerequisite to comparing scores on the different versions. In this
      study, we used exploratory structural equation modeling (ESEM) as an alternative
      approach to evaluate the measurement invariance of the Spanish version of the
      Physical Self-Description Questionnaire (PSDQ). The two versions were
      administered to large samples of Australian and Spanish adolescents. First, we
      compared the CFA and ESEM approaches and showed that ESEM fitted the data much
      better and resulted in substantially more differentiated factors. We then tested
      measurement invariance with a 13-model ESEM taxonomy. Results justified using the
      Spanish version of the PSDQ to carry out cross-cultural comparisons in sport and
      exercise psychology research. Overall, the study can stimulate research on
      physical self-concept across countries and foster better cross-cultural
      comparisons. 

PMID- 24686955
TI  - The ARSQ: the athletes' received support questionnaire.
AB  - To address calls for context-specific measurement of social support, this article
      reports the development of the Athletes' Received Support Questionnaire (ARSQ)
      and demonstrates initial evidence for its validity. Across four studies there was
      support for a four-dimensional structure reflecting emotional, esteem,
      informational, and tangible received support. There was also support for
      unidimensional and higher-order models. Further, Study 3 provided some support
      for convergent validity, with significant correlations between the corresponding
      dimensions of the ARSQ and the Inventory of Socially Supportive Behaviors. Study
      4 provided evidence for the nomological validity of the ARSQ. Emotional and
      esteem support significantly predicted self-confidence and positive affect, and
      tangible support significantly moderated the relationship between stress and
      negative affect. Collectively, these results provide initial evidence for the
      validity of the ARSQ, and offer researchers flexibility to adopt either a
      multidimensional or aggregated approach to measuring received support. 

PMID- 24686956
TI  - Exploring self-compassion and eudaimonic well-being in young women athletes.
AB  - Using a mixed methods research design, we explored self-compassion and eudaimonic
      well-being in young women athletes. In a quantitative study (n = 83), we found
      that self-compassion and eudaimonic well-being were positively related (r = .76,
      p < .01). A model of multiple mediation was proposed, with self-compassion,
      passivity, responsibility, initiative, and self-determination accounting for 83%
      of the variance in eudaimonic well-being. In a qualitative study (n = 11), we
      explored when and how self-compassion might be useful in striving to reach one's
      potential in sport. Self-compassion was described as advantageous in difficult
      sport-specific situations by increasing positivity, perseverance, and
      responsibility, as well as decreasing rumination. Apprehensions about fully
      embracing a self-compassionate mindset in sport warrant additional research to
      explore the seemingly paradoxical role of self-compassion in eudaimonic well
      being. 

PMID- 24686957
TI  - Self-affirmation promotes physical activity.
AB  - The present study tests whether a self-affirmation intervention (i.e., requiring
      an individual to focus on a valued aspect of their self-concept, such as honesty)
      can increase physical activity and change theory of planned behavior (TPB)
      variables linked to physical activity. Eighty young people completed a
      longitudinal intervention study. Baseline physical activity was assessed using
      the Godin Leisure-Time Physical Activity Questionnaire (LTPAQ). Next,
      participants were randomly allocated to either a self-affirmation or a
      nonaffirmation condition. Participants then read information about physical
      activity and health, and completed measures of TPB variables. One week later,
      participants again completed LTPAQ and TPB items. At follow up, self-affirmed
      participants reported significantly more physical activity, more positive
      attitudes toward physical activity, and higher intentions to be physically active
      compared with nonaffirmed participants. Neither attitudes nor intentions mediated
      the effects of self-affirmation on physical activity. Self-affirmation can
      increase levels of physical activity and TPB variables. Self-affirmation
      interventions have the potential to become relatively simple methods for
      increasing physical activity levels. 

PMID- 24686958
TI  - Manual signing in adults with intellectual disability: influence of sign
      characteristics on functional sign vocabulary.
AB  - PURPOSE: The purpose of this study was to investigate the influence of sign
      characteristics in a key word signing (KWS) system on the functional use of those
      signs by adults with intellectual disability (ID). METHOD: All 507 signs from a
      Flemish KWS system were characterized in terms of phonological, iconic, and
      referential characteristics. Phonological and referential characteristics were
      assigned to the signs by speech-language pathologists. The iconicity (i.e.,
      transparency, guessing the meaning of the sign; and translucency, rating on a 6
      point scale) of the signs were tested in 467 students. Sign functionality was
      studied in 119 adults with ID (mean mental age of 50.54 months) by means of a
      questionnaire, filled out by a support worker. RESULTS: A generalized linear
      model with a negative binomial distribution (with log-link) showed that semantic
      category was the factor with the strongest influence on sign functionality, with
      grammatical class, referential concreteness, and translucency also playing a
      part. No sign phonological characteristics were found to be of significant
      influence on sign use. CONCLUSION: The meaning of a sign is the most important
      factor regarding its functionality (i.e., whether a sign is used in everyday
      communication). Phonological characteristics seem only of minor importance.

PMID- 24686960
TI  - Creating a culture of safety.

PMID- 24686959
TI  - A population-based intervention for the prevention of falls and fractures in home
      dwelling people 65 years and older in South Germany: protocol.
AB  - BACKGROUND: Falls and fall-related injuries pose a major threat to older peoples'
      health, and are associated with increased morbidity and mortality. In the course
      of demographic changes, development and implementation of fall prevention
      strategies have been recognized as an urgent public health challenge. Various
      risk factors for falls and a number of effective interventions have been
      recognized. A substantial proportion of falls occur for people who are neither
      frail nor at high risk. Therefore, population-based approaches reaching the
      entire older population are needed. OBJECTIVE: The objective of the study
      presented is the development, implementation, and evaluation of a population
      based intervention for the prevention of falls and fall-related injuries in a
      medium sized city in Germany. METHODS: The study is designed as a population
      based approach. The intervention community is a mid sized city named Reutlingen
      in southern Germany with a population of 112,700 people. All community dwelling
      inhabitants 65 years and older are addressed. There are two main measures that
      are defined: (1) increase of overall physical activity, and (2) reduction of
      modifiable risk factors for falls such as deficits in strength and balance, home
      and environmental hazards, impaired vision, unsafe footwear, and improper use of
      assistive devices. The implementation strategies are developed in a participatory
      community planning process. These might include, for example, training of
      professionals and volunteers, improved availability of exercise classes, and
      education and raising awareness via newspaper, radio, or lectures. RESULTS: The
      study starts in September 2010 and ends in December 2013. It is evaluated
      primarily by process evaluation as well as by telephone survey. CONCLUSIONS:
      Physical activity as a key message entails multiple positive effects with
      benefits on a range of geriatric symptoms. The strength of the design is the
      development of implementation strategies in a participatory community planning.
      The problems that we anticipate are the dependency on the stakeholders'
      willingness to participate, and the difficulty of evaluating population-based
      programs by hard end points.

PMID- 24686961
TI  - Cognitive function.

PMID- 24686962
TI  - Authors' response.

PMID- 24686963
TI  - Safety first.

PMID- 24686964
TI  - Authors' response.

PMID- 24686966
TI  - Using stereophotogrammetric technology for obtaining intraoral digital
      impressions of implants.
AB  - BACKGROUND: The procedure for making impressions of multiple implants continues
      to be a challenge, despite the various techniques proposed to date. The authors'
      objective in this case report is to describe a novel digital impression method
      for multiple implants involving the use of stereophotogrammetric technology. CASE
      DESCRIPTION: The authors present three cases of patients who had multiple
      implants in which the impressions were obtained with this technology. Initially,
      a stereo camera with an infrared flash detects the position of special flag
      abutments screwed into the implants. This process is based on registering the x,
      y and z coordinates of each implant and the distances between them. This
      information is converted into a stereolithographic (STL) file. To add the soft
      tissue information, the user must obtain another STL file by using an intraoral
      or extraoral scanner. In the first case presented, this information was acquired
      from the plaster model with an extraoral scanner; in the second case, from a
      Digital Imaging and Communication in Medicine (DICOM) file of the plaster model
      obtained with cone-beam computed tomography; and in the third case, through an
      intraoral digital impression with a confocal scanner. RESULTS: In the three
      cases, the frameworks manufactured from this technique showed a correct clinical
      passive fit. At follow-up appointments held six, 12 and 24 months after insertion
      of the prosthesis, no complications were reported. CONCLUSIONS:
      Stereophotogrammetric technology is a viable, accurate and easy technique for
      making multiple implant impressions. PRACTICAL IMPLICATIONS: Clinicians can use
      stereophotogrammetric technology to acquire reliable digital master models as a
      first step in producing frameworks with a correct passive fit.

PMID- 24686965
TI  - Hospital-based emergency department visits involving dental conditions: profile
      and predictors of poor outcomes and resource utilization.
AB  - BACKGROUND: Untreated dental conditions may progress to lesions that are severe
      enough to necessitate emergency visits to hospitals. The authors conducted a
      study to investigate nationally representative trends in U.S. hospital-based
      emergency department (ED) visits involving dental conditions and to examine
      patient-related characteristics associated with ED charges. METHODS: The authors
      used the Nationwide Emergency Department Sample of the Healthcare Cost and
      Utilization Project, sponsored by the Agency for Healthcare Research and Quality,
      for the years 2008 through 2010. They selected all ED visits involving patients
      with a diagnosis of either dental caries, pulpal or periapical lesions, gingival
      or periodontal conditions, or mouth cellulitis or abscess. Outcomes examined
      included post-ED disposition status and hospital ED charges. RESULTS: During the
      study period, 4,049,361 ED visits involved diagnosis of a dental condition, which
      is about 1 percent of all ED visits occurring in the entire United States.
      Uninsured patients made about 40.5 percent of all dental condition-related ED
      visits. One hundred one patients in the study died in EDs. The mean hospital ED
      charge per visit was approximately $760 (adjusted to 2010 dollars), and the total
      ED charges across the entire United States during the three-year study period was
      $2.7 billion. CONCLUSIONS: Patients without insurance are a cohort at high risk
      of seeking dental care in hospital-based ED settings. A substantial amount of
      hospital resources are used to treat dental conditions in ED settings. Patients
      with mouth cellulitis, periodontal conditions and numerous comorbidities are
      likely to incur higher ED charges. PRACTICAL IMPLICATIONS: Dental conditions can
      be treated more effectively in a dental office setting than in hospital-based
      settings.

PMID- 24686968
TI  - Oral care behavior after purging in a sample of women with bulimia nervosa.
AB  - BACKGROUND: Bulimia nervosa (BN) is a mental health disorder associated with
      serious dental problems. The authors surveyed patients with a diagnosis of BN
      about their oral health behaviors after purging and their perspectives on
      barriers to patient-initiated discussion of eating disorders (EDs) with oral
      health professionals (OHPs). METHODS: A convenience sample of women with BN who
      were receiving treatment at major ED treatment centers (those centers that are
      members of the Academy of Eating Disorders, Deerfield, Ill.) completed a 45-item,
      self-reported online survey that the authors use to assess oral care behaviors
      after purging, dental problems and barriers to communication with their dentists.
      Inclusion criteria were being 18 years or older, female and a U.S. resident, as
      well as having a clinical diagnosis of BN. A sample of 292 women began the
      survey, and 201 (68.8 percent) completed the survey. RESULTS: The survey results
      indicated that 32.5 percent of participants reported brushing their teeth
      immediately after purging, which is contraindicated. Although 92.4 percent of
      participants acknowledged having dental problems, only 29.2 percent of these
      participants discussed their BN with a dentist. CONCLUSIONS: The survey results
      show that although participants with BN had a high level of concern about their
      oral health and a high incidence of oral health problems, less than one-third
      considered their OHPs to be the most helpful source of oral health information.
      PRACTICAL IMPLICATIONS: OHPs must be educated about how to approach patients when
      an ED is suspected, develop practice protocols for discussing secondary
      prevention with patients and develop practice policies about disclosing ED (for
      example, purging) to a parent or guardian.

PMID- 24686967
TI  - Association of calcified carotid atheromas visualized on panoramic images and
      aortic arch calcifications seen on chest radiographs of postmenopausal women.
AB  - BACKGROUND: Occult atherosclerotic disease is the leading cause of death among
      older women. The authors hypothesized that women with calcified carotid artery
      plaque (CCAP) visualized on panoramic images were more likely to have aortic arch
      calcifications (AAC) that were visible on chest radiographs (CRs), a risk
      indicator of experiencing cardiovascular events, than would matched cohorts who
      did not have atheromas. METHODS: The authors obtained the CRs of 36 female
      veterans (>= 50 years) who had CCAP and atherogenically risk-matched them to
      those of 36 women without CCAP. A radiologist evaluated the CRs for AAC. Other
      study variables included age, ethnicity, body mass index and presence or absence
      of hypertension, diabetes and dyslipidemia. The authors computed descriptive and
      bivariate statistics. RESULTS: Women 60 years or older who had evidence of CCAP
      on their panoramic radiographs were significantly (P = .022; 95 percent
      confidence interval, 1.298-26.223) more likely to have evidence of AAC on their
      CRs than were similarly aged women who did not have evidence of CCAP. This
      association was not evident in women younger than 60 years. Among women who were
      both younger and older than 60 years, there was no evident association between
      the presence of CCAP and the severity (on a four point scale [0-3]) of AAC
      calcification. CONCLUSION: Prevalence of carotid plaque on panoramic images of
      women 60 years or older is significantly associated with presence of aortic arch
      calcifications on CRs. PRACTICAL IMPLICATIONS: Panoramic images of women 60 years
      or older must be evaluated for CCAP, given their association with AAC. Patients
      with atheromas should be referred to their physicians for further evaluation
      given the systemic implications.

PMID- 24686971
TI  - Using drill stops on twist drills to promote safety and efficiency when creating
      osteotomies for dental implants.
AB  - BACKGROUND: A growing number of dental implants are being placed each year in the
      United States. This upward trend is associated with an increased incidence of
      comorbidities. In this regard, use of a drill stop has the potential to decrease
      unintended consequences of overdrilling the depth of an osteotomy. METHODS: The
      authors did not find any studies in the dental literature in which researchers
      assessed the safety and effectiveness of using drill stops on twist drills.
      Nevertheless, the advantages of utilizing drill stops and the undesired results
      due to excessive drilling can be reasonably deduced. RESULTS: The authors
      describe the following clinically relevant issues pertaining to overdrilling of
      osteotomies for dental implants: the anatomical effect of excessive drilling in
      different sections of the oral cavity, reasons for excessive drilling, methods to
      avoid overlengthening of implant sites and benefits of using drill stops on twist
      drills. CONCLUSIONS: Use of drill stops enhances safety, accuracy and efficiency
      when creating an osteotomy. Drill stops also reduce the clinicians and patients
      stress during operative procedures. PRACTICAL IMPLICATIONS: Drills stops can be
      beneficial when utilized in situations in which there is reduced visibility,
      making it difficult to read the lines on a twist drill. They also are helpful
      when there is a dearth of bone over the mandibular or mental nerves, and
      precisely lengthened osteotomies are needed to avoid nerve injuries.

PMID- 24686970
TI  - The effect of a nanofilled resin-based coating on water absorption by teeth
      restored with glass ionomer.
AB  - BACKGROUND: A nanofilled, resin-based light-cured coating (G-Coat Plus, GC
      America, Alsip, Ill.) may reduce water absorption by glass ionomers. The authors
      investigated this possibility by measuring cuspal flexure caused by swelling of
      glass ionomer-restored teeth. METHODS: The authors cut large mesio-occlusodistal
      slots (4-millimeter wide, 4-mm deep) in 12 extracted premolars and restored them
      with a glass ionomer cement (Fuji IX GP Extra, GC America). Six teeth were
      coated, and the other six were uncoated controls. The authors digitized the teeth
      in three dimensions by using an optical scanner after preparation and restoration
      and during an eight-week storage in water. They calculated cuspal flexure and
      analyzed the results by using an analysis of variance and Student-Newman-Keuls
      post hoc tests (significance level .05). They used dye penetration along the
      interface to verify bonding. RESULTS: Inward cuspal flexure indicated restoration
      shrinkage. Coated restorations had significantly higher flexure (mean [standard
      deviation], -11.9 [3.5] micrometers) than did restorations without coating (-7.3
      [1.5] MUm). Flexure in both groups decreased significantly (P < .05) during water
      storage and, after eight weeks, it changed to expansion for uncoated control
      restorations. Dye penetration along the interfaces was not significant, which
      ruled out debonding as the cause of cuspal relaxation. CONCLUSIONS: Teeth
      restored with glass ionomer cement exhibited shrinkage, as seen by inward cuspal
      flexure. The effect of the protective coating on water absorption was evident in
      the slower shrinkage compensation. PRACTICAL IMPLICATIONS: The study results show
      that teeth restored with glass ionomers exhibited setting shrinkage that deformed
      tooth cusps. Water absorption compensated for the shrinkage. Although the coating
      may be beneficial for reducing water absorption, it also slows the shrinkage
      compensation rate (that is, the rate that hygroscopic expansion compensates for
      cuspal flexure from shrinkage).

PMID- 24686972
TI  - Access flap surgery treatment for intrabony defects may result in improved
      clinical outcomes.

PMID- 24686973
TI  - A laboratory evaluation of dental unit water treatment systems.

PMID- 24686974
TI  - Health care reform brings new opportunities.

PMID- 24686969
TI  - Concordance between patient satisfaction and the dentist's view: findings from
      The National Dental Practice-Based Research Network.
AB  - OBJECTIVES: In this study, the authors examined the dentist's view of the
      patient's experience and concordance with the patient's rating of satisfaction.
      METHODS: Practitioners from 197 practices in The National Dental Practice-Based
      Research Network recruited consecutively seen patients who had defective
      restorations that were replaced or repaired. At the end of the dental visit, the
      treating dentist and 5,315 patients completed and returned a survey that asked
      about the patient's satisfaction. RESULTS: Most dentists viewed their patients as
      having been satisfied with the treatment experience (n = 4,719 [89 percent]) and
      as having perceived them as friendly (n = 5,136 [97 percent]). Dentists had less
      strong feelings about whether patients had a preference for the restorative
      material (n = 2,271 [43 percent]) or an interest in obtaining information about
      the procedure (n = 1,757 [33 percent]). Overall, patients were satisfied, and
      most of the time dentists correctly predicted this outcome. Among patients who
      were less than satisfied, there was a substantial subset of cases in which
      dentists were not aware of this dissatisfaction. CONCLUSION: For improved patient
      centered care, dentists should assess patients' desires, expectations and
      perceptions of the dental care experience and then manage or correct the
      expectations and perceptions as needed. PRACTICAL IMPLICATIONS: By taking a
      patient-centered approach, dentists should seek to understand how patients
      evaluate and rate the services provided, thereby enabling them to focus on what
      each patient values most.

PMID- 24686975
TI  - Use of luting or bonding with lithium disilicate and zirconia crowns.

PMID- 24686976
TI  - Can the 'wrong' team become the 'right' team?

PMID- 24686977
TI  - Addressing after-hours requests for prescription drugs.

PMID- 24686978
TI  - Lasers may reduce pain arising from dentin hypersensitivity.

PMID- 24686979
TI  - Hearing loss in syndromic craniosynostoses: introduction and consideration of
      mechanisms.
AB  - PURPOSE: There are a number of craniosynostosis syndromes with hearing loss
      including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with
      acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in
      the fibroblast growth factor receptor (FGFR) genes. Studies of FGFRs and their
      ligands, fibroblast growth factors (FGFs), have revealed clues to the precise
      contribution of aberrant FGFR signaling to inner ear morphogenesis and the
      hearing loss encountered in craniosynostoses. The purpose of this article is to
      review basic studies of FGFRs with emphasis on their function and expression in
      the inner ear and surrounding structures. METHOD: A Medline search was performed
      to find basic science articles regarding FGFR, their ligands, and their
      expression and relevant mouse models. Additional items searched included clinical
      descriptions and studies of individuals with FGFR-related craniosynostosis
      syndromes. RESULTS: The FGF signaling pathway is essential for the morphogensis
      and proper function of the inner ear and auditory sensory epithelium. CONCLUSION:
      The variable auditory phenotypes seen in individuals with Muenke syndrome may
      have a genetic basis, likely due to multiple interacting factors in the genetic
      environment or modifying factors. Further analysis and studies of mouse models of
      Muenke syndrome, in particular, may provide clues to the specific effects of the
      defining mutation in FGFR3 in the inner ear not only at birth but also into
      adulthood. In particular, investigations into these models may give insight into
      the variable expression and incomplete penetrance of this phenotype.

PMID- 24686980
TI  - A mouse tumor model of surgical stress to explore the mechanisms of postoperative
      immunosuppression and evaluate novel perioperative immunotherapies.
AB  - Surgical resection is an essential treatment for most cancer patients, but
      surgery induces dysfunction in the immune system and this has been linked to the
      development of metastatic disease in animal models and in cancer patients.
      Preclinical work from our group and others has demonstrated a profound
      suppression of innate immune function, specifically NK cells in the postoperative
      period and this plays a major role in the enhanced development of metastases
      following surgery. Relatively few animal studies and clinical trials have focused
      on characterizing and reversing the detrimental effects of cancer surgery. Using
      a rigorous animal model of spontaneously metastasizing tumors and surgical
      stress, the enhancement of cancer surgery on the development of lung metastases
      was demonstrated. In this model, 4T1 breast cancer cells are implanted in the
      mouse mammary fat pad. At day 14 post tumor implantation, a complete resection of
      the primary mammary tumor is performed in all animals. A subset of animals
      receives additional surgical stress in the form of an abdominal nephrectomy. At
      day 28, lung tumor nodules are quantified. When immunotherapy was given
      immediately preoperatively, a profound activation of immune cells which prevented
      the development of metastases following surgery was detected. While the 4T1
      breast tumor surgery model allows for the simulation of the effects of abdominal
      surgical stress on tumor metastases, its applicability to other tumor types needs
      to be tested. The current challenge is to identify safe and promising
      immunotherapies in preclinical mouse models and to translate them into viable
      perioperative therapies to be given to cancer surgery patients to prevent the
      recurrence of metastatic disease. 

PMID- 24686982
TI  - Characterizing vibratory kinematics in children and adults with high-speed
      digital imaging.
AB  - PURPOSE The aim of this study is to quantify and identify characteristic
      vibratory motion in typically developing prepubertal children and young adults
      using high-speed digital imaging. METHOD The vibrations of the vocal folds were
      recorded from 27 children (ages 5-9 years) and 35 adults (ages 21-45 years), with
      high speed at 4,000 frames per second for sustained phonation. Kinematic features
      of amplitude periodicity, time periodicity, phase asymmetry, spatial symmetry,
      and glottal gap index were analyzed from the glottal area waveform across mean
      and standard deviation (i.e., intercycle variability) for each measure. RESULTS
      Children exhibited lower mean amplitude periodicity compared to men and women and
      lower time periodicity compared to men. Children and women exhibited greater
      variability in amplitude periodicity, time periodicity, phase asymmetry, and
      glottal gap index compared to men. Women had lower mean values of amplitude
      periodicity and time periodicity compared to men. CONCLUSION Children differed
      both spatially but more temporally in vocal fold motion, suggesting the need for
      the development of children-specific kinematic norms. Results suggest more
      uncontrolled vibratory motion in children, reflecting changes in the vocal fold
      layered structure and aero-acoustic source mechanisms. 

PMID- 24686983
TI  - Decreased sensitivity to long-distance dependencies in children with a history of
      specific language impairment: electrophysiological evidence.
AB  - PURPOSE: One possible source of tense and agreement limitations in children with
      specific language impairment (SLI) is a weakness in appreciating structural
      dependencies that occur in many sentences in the input. This possibility was
      tested in the present study. METHOD: Children with a history of SLI (H-SLI; n =
      12; M = 9;7 [years;months]) and typically developing same-age peers (TD; n = 12;
      M = 9;7) listened to and made grammaticality judgments about grammatical and
      ungrammatical sentences involving either a local agreement error (e.g., "Every
      night they talks on the phone") or a long-distance finiteness error (e.g., "He
      makes the quiet boy talks a little louder"). Electrophysiological (ERP) and
      behavioral (accuracy) measures were obtained. RESULTS: Local agreement errors
      elicited the expected anterior negativity and P600 components in both groups of
      children. However, relative to the TD group, the P600 effect for the long
      distance finiteness errors was delayed, reduced in amplitude, and shorter in
      duration for the H-SLI group. The children's grammaticality judgments were
      consistent with the ERP findings. CONCLUSION: Children with H-SLI seem to be
      relatively insensitive to the finiteness constraints that matrix verbs place on
      subject-verb clauses that appear later in the sentence.

PMID- 24686984
TI  - Nanoscale structure study of boron nitride nanosheets and development of a deep
      UV photo-detector.
AB  - In this communication, we report on the synthesis of few atomic-layer boron
      nitride nanosheets (BNNSs) and their application for deep ultraviolet photo
      detection. Synthesis of BNNSs is carried out by using the short-pulse plasma beam
      deposition technique. High-resolution tunneling electron microscopy,
      cathodoluminescence spectroscopy and photo-stimulated measurements are conducted
      and linked to characterize the BNNS morphology. The obtained BNNSs are flat with
      a typical size of 50 * 50 MUm(2) and are optically transparent down to 210 nm.
      Nanoscale studies by transmission electron microscopy revealed that these
      nanosheets are composed of a densely packed honeycomb crystal lattice structure
      of covalently bonded boron and nitrogen atoms. Cathodoluminescence spectroscopy
      of these nanosheets revealed a single sharp excitonic peak centered at 233 nm at
      300 K. The synthesized BNNSs are used to demonstrate applicability of BNNSs for
      detecting ultraviolet photons. The initial experimental tests of the developed
      prototype BNNSs based deep-ultraviolet photo-detector show that it is blind to
      photons with an energy less than 4 eV. The calculated output power of the
      detector is approximately 2 MUW and the ratio between the output electrical power
      and the input optical power is ~1%. 

PMID- 24686981
TI  - Vocal fold epithelial barrier in health and injury: a research review.
AB  - PURPOSE: Vocal fold epithelium is composed of layers of individual epithelial
      cells joined by junctional complexes constituting a unique interface with the
      external environment. This barrier provides structural stability to the vocal
      folds and protects underlying connective tissue from injury while being nearly
      continuously exposed to potentially hazardous insults, including environmental or
      systemic-based irritants such as pollutants and reflux, surgical procedures, and
      vibratory trauma. Small disruptions in the epithelial barrier may have a large
      impact on susceptibility to injury and overall vocal health. The purpose of this
      article is to provide a broad-based review of current knowledge of the vocal fold
      epithelial barrier. METHOD: A comprehensive review of the literature was
      conducted. Details of the structure of the vocal fold epithelial barrier are
      presented and evaluated in the context of function in injury and pathology. The
      importance of the epithelial-associated vocal fold mucus barrier is also
      introduced. RESULTS/CONCLUSIONS: Information presented in this review is valuable
      for clinicians and researchers as it highlights the importance of this
      understudied portion of the vocal folds to overall vocal health and disease.
      Prevention and treatment of injury to the epithelial barrier is a significant
      area awaiting further investigation.

PMID- 24686985
TI  - A diazirine-based photoaffinity probe for facile and efficient aptamer-protein
      covalent conjugation.
AB  - A photo-reactive functional labelling reagent, diazirine phosphoramidite, was
      designed and synthesized for easy and flexible site-specific labelling of
      oligonucleotides with the diazirine moiety. The new reagent allows facile photo
      crosslinking of oligonucleotide with its interacting partner for a variety of
      applications, including tertiary structure determination, molecular interaction
      study and biomarker discovery. 

PMID- 24686986
TI  - Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with
      GVHD.
AB  - GVHD is a major complication following allogeneic hematopoietic SCT, and is
      associated with substantial morbidity and mortality. Based on the results of our
      previous clinical study with females treated with human chorionic gonadotropin
      (hCG) as preconditioning therapy for in vitro fertilization, we hypothesized that
      low-dose hCG stimulates indoleamine-2,3-dioxygenase (IDO), IL 10 and regulatory T
      cells (Treg), thereby suppressing clinical manifestations of chronic GVHD. Active
      chronic GVHD localized at skin, subcutaneous tissue, joints or gastrointestinal
      tract that was refractory or intolerant to glucocorticoid therapy improved
      substantially in 12 of 20 patients treated with hCG for 8 weeks (off-label),
      enabling a glucocorticoid dose reduction of 28% (average). Twelve of 19 patients
      with chronic GVHD of the skin responded to hCG therapy with a reduction of 25%
      (average) in their total skin score. HCG treatment increased IDO expression at
      median by sevenfold in peripheral mononuclear cells and IL10 levels in serum up
      to twofold at median from the pretreatment baseline. Further, an expansion of the
      Treg cell population was measured in one patient, which is also associated with
      the induction of tolerance. This novel application of low-dose hCG was well
      tolerated and is of clinical interest for GVHD treatment.

PMID- 24686987
TI  - Impact of uncontrolled freezing and long-term storage of peripheral blood stem
      cells at - 80  degrees C on haematopoietic recovery after autologous
      transplantation. Report from two centres.
AB  - Controlled-rate freezing and storage in vapour phase nitrogen are used by most
      transplantation teams for the cryopreservation and storage of peripheral blood
      haematopoietic stem cells (PBSC). In this study, we analysed 666 autologous PBSC
      transplants after uncontrolled freezing and storage of PBSC at -80  degrees C.
      Statistical analysis showed that neutrophil recovery was associated with both the
      infused CD34(+) cell dose (P=0.01) and the post transplantation use of growth
      factors (P<0.001) and that platelet recovery was associated with the infused
      CD34(+) cell dose (P<0.001) and with the diagnosis (P=0.02). We analysed three
      groups according to the duration of the cryopreservation period (less than 6
      months, between 6 and 12 months or more than 1 year). Haematopoietic recovery was
      not found to be adversely affected by longer storage at -80  degrees C. The
      haematopoietic recoveries of 50 pairs of sequential transplantations from the
      same PBSC mobilization were analysed. Despite prolonged cryopreservation, there
      were no statistically significant differences in neutrophil (P=0.09) or platelet
      (P=0.22) recovery in the second compared with the first transplant. In
      conclusion, the long-term storage of PBSC at -80  degrees C after uncontrolled
      rate freezing is an easy and comparatively inexpensive cryopreservation method
      that leads to successful haematopoietic recovery even after prolonged storage. 

PMID- 24686989
TI  - Autonomic correlates of speech versus nonspeech tasks in children and adults.
AB  - PURPOSE: To assess autonomic arousal associated with speech and nonspeech tasks
      in school-age children and young adults. METHOD: Measures of autonomic arousal
      (electrodermal level, electrodermal response amplitude, blood pulse volume, and
      heart rate) were recorded prior to, during, and after the performance of speech
      and nonspeech tasks by twenty 7- to 9-year-old children and twenty 18- to 22-year
      old adults. RESULTS: Across age groups, autonomic arousal was higher for speech
      tasks compared with nonspeech tasks, based on peak electrodermal response
      amplitude and blood pulse volume. Children demonstrated greater relative arousal,
      based on heart rate and blood pulse volume, for nonspeech oral motor tasks than
      adults but showed similar mean arousal levels for speech tasks as adults.
      Children demonstrated sex differences in autonomic arousal; specifically,
      autonomic arousal remained high for school-age boys but not girls in a more
      complex open-ended narrative task that followed a simple sentence production
      task. CONCLUSIONS: Speech tasks elicit greater autonomic arousal than nonspeech
      tasks, and children demonstrate greater autonomic arousal for nonspeech oral
      motor tasks than adults. Sex differences in autonomic arousal associated with
      speech tasks in school-age children are discussed relative to speech-language
      differences between boys and girls.

PMID- 24686990
TI  - Residual shear deformations in the coronary artery.
AB  - Quantifying arterial residual deformations is critical for understanding the
      stresses and strains within the arterial wall during physiological and
      pathophysiological conditions. This study presents novel findings on residual
      shear deformations in the left anterior descending coronary artery. Residual
      shear deformations are most evident when thin, long axial strips are cut from the
      artery. These strips deform into helical configurations when placed in isotonic
      solution. A residual shear angle is introduced as a parameter to quantify the
      residual shear deformations. Furthermore, a stress analysis is performed to study
      the effects of residual shear deformations on the intramural shear stress
      distribution of an artery subjected to pressure, axial stretch, and torsion using
      numerical simulation. The results from the stress analyses suggest that residual
      shear deformations can significantly modulate the intramural shear stress across
      the arterial wall.

PMID- 24686992
TI  - Efficacy assessment of cryostorants of donor hearts by ImageJ based image
      analysis.
AB  - AIM: Donor organ injury during cold preservation before transplantation
      negatively impacts graft survival. The current study was to examine available
      evidences for the efficacy of different cold storage solutions that are used to
      preserve donor hearts in vitro prior to orthotopic transplantation. METHODS: A
      systematic search of full-length articles published from 1980 to August 2012 was
      performed in PubMed and Google Scholar. Detailed searches were also made for
      availability of any sourceware for histopathology images of endomyocardial
      biopsies of stored hearts. RESULTS: Not even a single controlled trial has been
      published relating to this topic. However, we assessed all available literature
      pertaining to this topic, and performed original, simple yet innovative analyses
      using ImageJ, a Java based image analyses program, to show the tremendous power
      to objectively examine the efficacy of the storage solution. Our analysis suggest
      that ImageJ may be conveniently used to obtain evidences (or lack of it) of
      ischemic injury of donor hearts during cold storage. CONCLUSION: Even the UNOS
      database does not provide histopathological evidences of cardiac biopsies of
      orthotopically transplanted hearts. We, however, make the case of the need for
      image analyses and making availability of images to allow establishing evidence
      of the usefulness of these storage solutions. We recommend obtaining
      endomyocardial biopsy prior to orthotopic transplantation and create a registry
      of H&E stained slides. This is the only step that will direct us towards evidence
      based care of such highly critical patients who need the equally challenging
      surgical intervention of cardiac transplantation.

PMID- 24686988
TI  - Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma
      patients: a position statement from the European Group for Blood and Marrow
      Transplantation.
AB  - Autologous haematopoietic SCT with PBSCs is regularly used to restore BM function
      in patients with multiple myeloma or lymphoma after myeloablative chemotherapy.
      Twenty-eight experts from the European Group for Blood and Marrow Transplantation
      developed a position statement on the best approaches to mobilising PBSCs and on
      possibilities of optimising graft yields in patients who mobilise poorly.
      Choosing the appropriate mobilisation regimen, based on patients' disease stage
      and condition, and optimising the apheresis protocol can improve mobilisation
      outcomes. Several factors may influence mobilisation outcomes, including older
      age, a more advanced disease stage, the type of prior chemotherapy (e.g.,
      fludarabine or melphalan), prior irradiation or a higher number of prior
      treatment lines. The most robust predictive factor for poor PBSC collection is
      the CD34(+) cell count in PB before apheresis. Determination of the CD34(+) cell
      count in PB before apheresis helps to identify patients at risk of poor PBSC
      collection and allows pre-emptive intervention to rescue mobilisation in these
      patients. Such a proactive approach might help to overcome deficiencies in stem
      cell mobilisation and offers a rationale for the use of novel mobilisation
      agents. 

PMID- 24686993
TI  - Efficacy and safety assessment of isolated ultrafiltration compared to
      intravenous diuretics for acutely decompensated heart failure: a systematic
      review with meta-analysis.
AB  - AIM: Intravenous diuretics at relatively high doses are currently used for
      treating acute decompensated heart failure (ADHF). However, the existence of
      harmful side effects diuretic-related, such as electrolyte abnormalities,
      symptomatic hypotension and marked neuro-hormonal activation have led researchers
      to implement alternative therapeutic tools such as isolated ultrafiltration
      (IUF). METHODS: Our study aimed to compare intravenous diuretics vs. IUF as
      regards their respective efficacy and safety in ADHF patients through systematic
      review and meta-analysis of data derived from relevant randomized controlled
      trials. RESULTS: 6 studies grouping a total of 477 patients were included in the
      systematic review. By contrast, data from only three studies were pooled for the
      meta-analysis, because of different adopted outcomes or marked dissimilarities in
      the data presentation . Weight loss at 48 h was greater in IUF group compared to
      the diuretics group [weighted mean difference (WMD)=1.77 kg; 95%CI: 1.18-2.36 kg;
      P<0.001)]. Similarly, greater fluid loss at 48 h was found in IUF group in
      comparison with diuretics group (WMD=1.2 liters; 95%CI: 0.73-1.67 liters; P<
      0.001). In contrast, the probability of exhibiting worsening renal function
      (WRF), i.e., increase in serum creatinine > 0.3 mg/dl at 48 hours, was similar to
      the one found in the diuretics group (OR=1.33; 95% CI: 0.81-2.16 P=0.26).
      CONCLUSION: On the basis of this meta-analysis, IUF induced greater weight loss
      and larger fluid removal compared to iv diuretics in ADHF patients, whereas the
      probability of developing WRF was not significantly different in the comparison
      between iv diuretics and IUF.

PMID- 24686994
TI  - Possible role of BNP for an early diagnosis of asymptomatic left ventricular
      dysfunction: a retrospective study.
AB  - AIM: The use of haematochemical markers of intra-ventricular myocardial strain,
      known as B-type natriuretic peptides, has been proposed as an initial diagnostic
      step for early screening programs targeting asymptomatic left ventricular
      dysfunction (ALVD) in populations of subjects at risk. METHODS: The diagnostic
      accuracy of BNP for the identification of ALVD was assessed by adopting Doppler
      echocardiography supplemented by Doppler Tissue Imaging (DTI) as the gold
      standard method. For this purpose, a retrospective analysis of the medical
      records of patients judged at risk of ALVD, mostly hypertensive and/or diabetic
      patients, was carried out. For admission into the study, at least one
      determination of plasma BNP and one Doppler echocardiographic assessment
      complemented by DTI were required for each patient. Systolic ALVD was diagnosed
      in the presence of left ventricular ejection fraction(LVEF) of <50 %. Diastolic
      ALVD was assessed according to the recommendations of the American Society of
      Echocardiography using two-dimensional Doppler echocardiography and TDI. Thus, in
      the presence of LVEF of >=50%, concomitant findings of lateral mitral annular e'
      velocity <10 cm/s and septal mitral annular e' velocity <8 cm/s with left atrial
      volume index >=34 ml/m2 were required to substantiate a diagnosis of diastolic
      ALVD . It was subsequently graded by measuring the ratio of early (E) to late (A)
      transmitral flow velocity (E/A ratio), mitral deceleration time and E/average e'
      ratio. Several Receiver Operating Characteristic (ROC) curves were built in the
      entire study population as well as in some subsets, to identify the BNP values
      exhibiting the best profile of sensitivity, specificity and positive and negative
      likelihood ratios with respect to ALVD. RESULTS: Among 88 patients at risk
      enrolled on the whole, 33 cases (37.5%) of mild diastolic ALVD and 10 cases
      (11.4%) of moderate-to-severe diastolic ALVD were found. No cases of systolic
      ALVD were detected. The ROC plots for the diagnostic accuracy of serum BNP in
      early detection of ALVD in the entire cohort of patients at risk of heart failure
      showed an area under the curve of 0.761 [standard error=0.0523; P<0.0001 ] .
      Moreover, among the various BNP values located across the ROC curve, an optimal
      cut-off value of 156 pg/ml was found (sensitivity=83.7%; specificity=46.7%;
      positive likelihood ratio=1.57; negative likelihood ratio=0.35). Conversely, a
      value of 290 pg/ml was shown to be more specific at the cost of a remarkable loss
      in sensitivity (sensitivity=53.5%;specificity=95.5%; positive likelihood
      ratio=12; negative likelihood ratio=0.5). CONCLUSION: The sensitivity of BNP in
      the identification of patients with ALVD by adopting a cut-off of 156 pg/ml was
      equal to 83.7%, which is in keeping with the literature values. In case of
      programs targeted to ALVD screening, the choice of adopting a relatively low
      threshold value for BNP seems to comply with the goal of enhancing sensitivity ,
      so as to exclude from the echocardiography the individuals found negative at BNP
      assay and thereby reduce the number of unnecessary echocardiographic examinations
      in individuals with low probability of having ALVD.

PMID- 24686995
TI  - Detection of ischemical dyssynchrony in patients with normal duration of QRS at
      rest and during exercise echocardiography (Dyssynchrony in coronary artery
      disease patients during exercise).
AB  - AIM: Ischemic segments cannot develop a sufficient amount of strength during
      systole, so theoretically they begin to contract later in comparison with non
      ischemic zones. There is a lack of information about methods that can detect
      dyssynchrony during exercise in patients with QRS not longer 100 ms. The aim of
      the study was to compare different methods of detection regarding left
      ventricular moving dyssynchrony in patients with significant coronary stenosis
      artery lesions: pulsed-wave of PW-TDI, strain (S) and strain rate (SR). METHODS:
      The study included 133 subjects: 106 consecutive patients who were scheduled for
      coronary angiography with previous stress-echocardiography and 27 healthy
      persons. All the patients underwent a supine bicycle exercise test. RESULTS:
      Seventy-six patients had stenoses and 30 subjects had no significant lesions by
      coronary angiography. There was a detectable difference between time parameters
      of left ventricle contraction for the two groups and controls before and during
      exercise using all Doppler methods. Subgroups of patients without previous
      myocardial infarction and without hypertrophy of left ventricle had the same
      results. Maximal difference was observed using strain method. There was a
      moderate correlation between time parameters and the existence of significant
      lesions of coronary arteries. CONCLUSION: Patients without prolongations of QRS
      with significant lesions of coronary arteries have detectable left ventricular
      dyssynchrony before and during exercise.

PMID- 24686996
TI  - Comprehensive multidisciplinary patient assessment and selection before TAVI
      procedure.
AB  - Aortic stenosis is a common disorder that affects nearly 5% of persons >75 years
      of age. Aortic valve replacement is indicated for symptomatic patients with
      severe aortic stenosis, as the prognosis of untreated patients is poor.
      Nevertheless, many patients with symptomatic severe aortic stenosis do not
      undergo surgical valve replacement, which has been attributed to comorbidities.
      Transcatheter aortic valve implantation (TAVI) is a novel method to treat
      selected high-risk patients with aortic stenosis. Patient screening and anatomic
      measurements of the aortic root are of great importance to ensure procedural
      success and appropriate patient selection. This review outlines comprehensive
      multidisciplinary assessment and selection of these patients and the evolving
      role of the echocardiogram and the multislice computed tomography in support of
      TAVI program. 

PMID- 24686997
TI  - New perspectives for transcatheter aortic valve implantation: more than a
      "simple" alternative to surgery.
AB  - To date, the gold standard of aortic stenosis treatment is surgical valve
      replacement. However, in inoperable or high risk patients a valid alternative is
      transcatheter aortic valve implantation (TAVI). Several trials showed
      feasibility, efficacy and safety of TAVI, with a tailored strategy for these
      patients on the basis of their clinical and anatomical conditions. The selection
      of valve type (CoreValve(r) or Edwards Sapien(r)) and transcatheter approach
      (transfemoral, transapical, subclavian or direct aortic approach) is an important
      step in the management of aortic stenosis. However, mortality is high and it is
      mainly related to non-cardiac reasons, given the high clinical risk profile of
      these patients. Moreover, the less invasive approach, the faster recovery, the
      reduced morbidity and the improved psychological tolerance, typical of TAVI,
      suggest that this technique could be used in a broader spectrum of cases,
      becoming a valid therapeutic alternative even in patients with severe aortic
      stenosis with a low surgical risk or asymptomatics. The identification of aortic
      stenosis patients by the medical community and their assessment over time, before
      they become candidates only for "extreme" strategies, remains the main challenge.

PMID- 24686998
TI  - The most relevant complications of transcatheter aortic valve implantation
      according to VARC criteria.
AB  - Transcatheter aortic valve implantation (TAVI) has been shown to be a viable
      alternative for high-risk patients who may not tolerate a surgical aortic valve
      replacement. The Edwards Sapien valve and the CoreValve are the most widely
      implanted valves worldwide. The indication may be expanded to intermediate and
      eventually low-risk patients in future; however, this will require a better
      understanding of potential complications and selecting the right valve for each
      individual patient. Although TAVI has expanded physicians' ability to intervene
      in many high-risk patients, there are still circumstances under which this
      procedure should not be considered, and some drawbacks have been identified,
      including important differences in periprocedural risks, aortic regurgitation,
      stroke, kidney injury, access associated complications, and significant
      conduction disturbances. One major concern is the higher rate of paravalvular
      leakage compared to SAVR. The Valve Academic Research Consortium established an
      independent collaboration between Academic Research organizations and specialty
      societies (cardiology and cardiac surgery) in the US and Europe. Consensus
      criteria were developed for the following endpoints: mortality, myocardial
      infarction, stroke, bleeding, acute kidney injury, vascular complications, and
      prosthetic valve performance. VARC definitions have already been incorporated
      into research and clinical practice. However, as clinical experience with this
      technology has matured and expanded, certain definitions have become unsuitable
      or ambiguous. The VARC 2 recommendations try to define the following clinical
      endpoints: mortality, stroke, myocardial infarction, bleeding complications,
      acute kidney injury, vascular complications, conduction disturbances, and
      arrhythmias, as well as a miscellaneous category including relevant complications
      not otherwise categorized. This manuscript reviews the most relevant
      complications of TAVI-transapical and transfemoral. 

PMID- 24686999
TI  - Percutaneous rheolytic thrombectomy with the AngioJet System for the treatment of
      intermediate-risk acute pulmonary embolism: a case report and an appraisal of
      contemporary indications and technique.
AB  - Percutaneous mechanical thrombectomy (PMT) for treatment of clinically
      significant pulmonary embolism (PE) has been shown to be technically feasible and
      effective, aiming at thrombus resolution without increase in major bleeding.
      Despite its success, use of PMT in clinical practise has not become widespread,
      because it is challenging. Among several devices proposed, AngioJet rheolytic
      thrombectomy (ART) appears as the most effective and easy-to-use. We present the
      case of a 69-year-old woman who developed acute intermediate-risk PE, with right
      ventricular dysfunction and major myocardial necrosis, who was successfully
      treated by ART. The peculiarities of the case, toghether with the principles,
      tecnique and tips and tricks of ART, its effectiveness and potential
      complications are discussed. 

PMID- 24687000
TI  - Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor
      blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events
      in patients with diabetes mellitus: a meta-analysis.
AB  - IMPORTANCE: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II
      receptor blockers (ARBs) may have different effects on cardiovascular (CV) events
      in patients with diabetes mellitus (DM). OBJECTIVE: To conduct a meta-analysis to
      separately evaluate the effects of ACEIs and ARBs on all-cause mortality, CV
      deaths, and major CV events in patients with DM. DATA SOURCES Data sources
      included MEDLINE (1966-2012), EMBASE (1988-2012), the Cochrane Central Register
      of Controlled Trials, conference proceedings, and article reference lists. STUDY
      SELECTION: We included randomized clinical trials reporting the effects of ACEI
      and ARB regimens for DM on all-cause mortality, CV deaths, and major CV events
      with an observation period of at least 12 months. Studies were excluded if they
      were crossover trials. DATA EXTRACTION AND SYNTHESIS: Dichotomous outcome data
      from individual trials were analyzed using the risk ratio (RR) measure and its
      95% CI with random-effects models. We estimated the difference between the
      estimates of the subgroups according to tests for interaction. We performed meta
      regression analyses to identify sources of heterogeneity. MAIN OUTCOMES AND
      MEASURES: Primary end points were all-cause mortality and death from CV causes.
      Secondary end points were the effects of ACEIs and ARBs on major CV events.
      RESULTS: Twenty-three of 35 identified trials compared ACEIs with placebo or
      active drugs (32,827 patients) and 13 compared ARBs with no therapy (controls)
      (23,867 patients). When compared with controls (placebo/active treatment), ACEIs
      significantly reduced the risk of all-cause mortality by 13% (RR, 0.87; 95% CI,
      0.78-0.98), CV deaths by 17% (0.83; 0.70-0.99), and major CV events by 14% (0.86;
      0.77-0.95), including myocardial infarction by 21% (0.79; 0.65-0.95) and heart
      failure by 19% (0.81; 0.71-0.93). Treatment with ARBs did not significantly
      affect all-cause mortality (RR, 0.94; 95% CI, 0.82-1.08), CV death rate (1.21;
      0.81-1.80), and major CV events (0.94; 0.85-1.01) with the exception of heart
      failure (0.70; 0.59-0.82). Both ACEIs and ARBs were not associated with a
      decrease in the risk for stroke in patients with DM. Meta-regression analysis
      showed that the ACEI treatment effect on all-cause mortality and CV death did not
      vary significantly with the starting baseline blood pressure and proteinuria of
      the trial participants and the type of ACEI and DM. CONCLUSIONS AND RELEVANCE:
      Angiotensin-converting enzyme inhibitors reduced all-cause mortality, CV
      mortality, and major CV events in patients with DM, whereas ARBs had no benefits
      on these outcomes. Thus, ACEIs should be considered as first-line therapy to
      limit excess mortality and morbidity in this population.

PMID- 24687001
TI  - Associations between toddler-age communication and kindergarten-age self
      regulatory skills.
AB  - PURPOSE: In this study, the authors aimed at gaining understanding on the
      associations of different types of early language and communication profiles with
      later self-regulation skills by using longitudinal data from toddler age to
      kindergarten age. METHOD: Children with early language profiles representing
      expressive delay, broad delay (i.e., expressive, social, and/or symbolic), and
      typical language development were compared in domains of kindergarten-age
      executive and regulative skills (attentional/executive functions, regulation of
      emotions and behavioral activity, and social skills) assessed with parental
      questionnaires. RESULTS: Children with delay in toddler-age language development
      demonstrated poorer kindergarten-age self-regulation skills than children with
      typical early language development. Broad early language delays were associated
      with compromised social skills and attentional/executive functions, and early
      expressive delays were associated with a generally lower level of kindergarten
      age executive and regulative skills. Regression analyses showed that both earlier
      and concurrent language had an effect especially on the attentional/executive
      functions. CONCLUSIONS: The findings suggest that different aspects of toddler
      age language have differential associations with later self-regulation. Possible
      mechanisms linking early language development to later self-regulative
      development are discussed.

PMID- 24687002
TI  - Reduced plant nutrition under elevated CO2 depresses the immunocompetence of
      cotton bollworm against its endoparasite.
AB  - Estimating the immunocompetence of herbivore insects under elevated CO2 is an
      important step in understanding the effects of elevated CO2 on crop-herbivore
      natural enemy interactions. Current study determined the effect of elevated CO2
      on the immune response of Helicoverpa armigera against its parasitoid Microplitis
      mediator. H. armigera were reared in growth chambers with ambient or elevated
      CO2, and fed wheat grown in the concentration of CO2 corresponding to their
      treatment levels. Our results showed that elevated CO2 decreases the nutritional
      quality of wheat, and reduces the total hemocyte counts and impairs the capacity
      of hemocyte spreading of hemolymph of cotton bollworm larvae, fed wheat grown in
      the elevated CO2, against its parasitoid; however, this effect was insufficient
      to change the development and parasitism traits of M. mediator. Our results
      suggested that lower plant nutritional quality under elevated CO2 could decrease
      the immune response of herbivorous insects against their parasitoid natural
      enemies. 

PMID- 24687004
TI  - Self-powered electrochemical memristor based on a biofuel cell--towards
      memristors integrated with biocomputing systems.
AB  - The electrochemical memristor based on a pH-switchable polymer-modified electrode
      integrated with a biofuel cell was designed and proposed for interfacing between
      biomolecular information processing and electronic systems. The present approach
      demonstrates a new application of biofuel cells in information processing
      systems, rather than for electrical power generation. 

PMID- 24687003
TI  - Segmental and prosodic approaches to accent management.
AB  - PURPOSE: This study investigated the relative outcomes of segmental and prosodic
      training of nonnative speakers of American English. METHOD: The study used a
      single-subject, alternating treatments, multiple baseline design with replication
      across participants and counterbalanced for order effect. Participants were 4
      adult male native Hindi speakers proficient in English. Two participants received
      ABABCACA (A = baseline/withdrawal, B = segmental training, C = prosody training),
      and 2 participants received ACACBABA, with a minimum of 5 sessions per phase.
      Segmental accuracy and prosodic accuracy were probed at each session, as were
      perception of accentedness and ease of understanding. RESULTS: Visual assessment
      of data and effect size calculation demonstrated that segmental and prosody
      training resulted in increased accuracy of pronunciation and prosody patterns,
      respectively, and those improvements appeared to be maintained over the short
      term. Listeners perceived lesser accent and easier understanding as a result of
      the combination of segmental and prosody training. The findings are uncertain
      with respect to the relative contribution of segmental and prosody training, and
      they may be speaker dependent, but the data do suggest that both components are
      important. CONCLUSION: Accent management, consisting of both segmental and
      prosody training, yielded positive outcomes. Further research with native
      language speakers of other languages is important to verify and expand on these
      findings.

PMID- 24687005
TI  - Transforming practices: a primer on action research.
AB  - Action research (AR) is a powerful tool for health education and promotion
      practitioners who want to focus on improving the quality of their programs and
      services. In this Tool, we describe the characteristics and controversial aspects
      of AR, differentiate between traditional and action research, present the
      benefits of applying AR methods/techniques for investigating problems related to
      professional practice, and offer a four-phase methodological framework for
      conducting AR studies. Unlike traditional research, AR is a methodology that
      links theory, research, and practice; advances new knowledge and understandings
      via iterative action cycles; employs frontline health practitioners as
      researchers; and promotes collaborative practitioner-community partnerships.
      Egalitarian in its approach, AR offers an "insider's perspective" centered on
      context-specific problems and issues related to health promotion. AR falls into
      two categories: large-scale community-based research and small-scale practice
      based research. Each cycle of the AR framework includes four phases: (a)
      preplanning/needs assessment, (b) planning/study organization, (c) action and
      observation/study implementation, and (d) reflection and planning/data analysis
      and interpretation. Using the AR primer in this Tool has the potential to empower
      health education/promotion practitioners, encourage collaborative partnerships,
      enhance practitioners' knowledge base, and promote social change. 

PMID- 24687006
TI  - HIV-, HCV-, and co-infections and associated risk factors among drug users in
      southwestern China: a township-level ecological study incorporating spatial
      regression.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      are major public health problems. Many studies have been performed to investigate
      the association between demographic and behavioral factors and HIV or HCV
      infection. However, some of the results of these studies have been in conflict.
      METHODOLOGY/PRINCIPAL FINDINGS: The data of all entrants in the 11 national
      methadone clinics in the Yi Autonomous Prefecture from March 2004 to December
      2012 were collected from the national database. Several spatial regression models
      were used to analyze specific community characteristics associated with the
      prevalence of HIV and HCV infection at the township level. The study enrolled
      6,417 adult patients. The prevalence of HIV infection, HCV infection and co
      infection was 25.4%, 30.9%, and 11.0%, respectively. Prevalence exhibited stark
      geographical variations in the area studied. The four regression models showed Yi
      ethnicity to be associated with both the prevalence of HIV and of HIV/HCV co
      infection. The male drug users in some northwestern counties had greater odds of
      being infected with HIV than female drug users, but the opposite was observed in
      some eastern counties. The 'being in drug rehabilitation variable was found to be
      positively associated with prevalence of HCV infection in some southern
      townships, however, it was found to be negatively associated with it in some
      northern townships. CONCLUSIONS/SIGNIFICANCE: The spatial modeling creates better
      representations of data such that public health interventions must focus on areas
      with high frequency of HIV/HCV to prevent further transmission of both HIV and
      HCV.

PMID- 24687007
TI  - Modeling the biomechanical influence of epilaryngeal stricture on the vocal
      folds: a low-dimensional model of vocal-ventricular fold coupling.
AB  - PURPOSE Physiological and phonetic studies suggest that, at moderate levels of
      epilaryngeal stricture, the ventricular folds impinge upon the vocal folds and
      influence their dynamical behavior, which is thought to be responsible for
      constricted laryngeal sounds. In this work, the authors examine this hypothesis
      through biomechanical modeling. METHOD The dynamical response of a low
      dimensional, lumped-element model of the vocal folds under the influence of vocal
      ventricular fold coupling was evaluated. The model was assessed for F0 and cover
      mass phase difference. Case studies of simulations of different constricted
      phonation types and of glottal stop illustrate various additional aspects of
      model performance. RESULTS Simulated vocal-ventricular fold coupling lowers F0
      and perturbs the mucosal wave. It also appears to reinforce irregular patterns of
      oscillation, and it can enhance laryngeal closure in glottal stop production.
      CONCLUSION The effects of simulated vocal-ventricular fold coupling are
      consistent with sounds, such as creaky voice, harsh voice, and glottal stop, that
      have been observed to involve epilaryngeal stricture and apparent contact between
      the vocal folds and ventricular folds. This supports the view that vocal
      ventricular fold coupling is important in the vibratory dynamics of such sounds
      and, furthermore, suggests that these sounds may intrinsically require
      epilaryngeal stricture. 

PMID- 24687008
TI  - Nanometer precise adjustment of the silver shell thickness during automated Au-Ag
      core-shell nanoparticle synthesis in micro fluid segment sequences.
AB  - In this work, a wet-chemical synthesis method for gold-silver core-shell
      particles with nanometer precise adjustable silver shell thicknesses is
      presented. Typically wet-chemical syntheses lead to relatively large diameter
      size distributions and losses in the yield of the desired particle structure due
      to thermodynamical effects. With the here explained synthesis method in micro
      fluidic segment sequences, a combinatorial in situ parameter screening of the
      reactant concentration ratios by programmed flow rate shifts in conjunction with
      efficient segment internal mixing conditions is possible. The highly increased
      mixing rates ensure a homogeneous shell deposition on all presented gold core
      particles while the amount of available silver ions was adjusted by automated
      flow rate courses, from which the synthesis conditions for exactly tunable shell
      thicknesses between 1.1 and 6.1 nm could be derived. The findings according to
      the homogeneity of size and particle structure were confirmed by differential
      centrifugal sedimentation (DCS), scanning and transmission electron microscopy
      (SEM, TEM) and X-ray photoelectron spectroscopy (XPS) measurements. In UV-Vis
      measurements, a significant contribution of the core metal was found in the shape
      of the extinction spectra in the case of thin shells. These results were
      confirmed by theoretical calculations. 

PMID- 24687009
TI  - An intake of C14-labelled dichlorobenzene.
AB  - An intake of C14 in the form of dichlorobenzene was followed up with 90 spot
      urine samples over a period of almost 2 weeks. This dataset has been fitted by a
      model consisting of three exponential terms. The intake and effective dose have
      been calculated. This case has been used to examine the effects of recent
      proposals by ICRP concerning the calculation of effective dose and the use of non
      standard biokinetic models. 

PMID- 24687010
TI  - Is hip strength a risk factor for patellofemoral pain? A systematic review and
      meta-analysis.
AB  - OBJECTIVE: To evaluate and synthesise the literature on hip strength among
      patients with patellofemoral pain (PFP) to address the following: (1)
      differentiate between hip strength as a risk factor and associated deficit in
      PFP; (2) describe hip strength in men and women with PFP across different age
      ranges; (3) investigate the effects of hip strengthening on biomechanical knee
      variables associated with PFP development. METHODS: MEDLINE, CINAHL, Web of
      Science, SportDiscus and Google Scholar were searched in November 2013 for
      studies investigating hip strength among patients with PFP. Two reviewers
      independently assessed papers for inclusion and quality. Means and SDs were
      extracted from each included study to allow effect size calculations and
      comparisons of results. RESULTS: Moderate-to-strong evidence from prospective
      studies indicates no association between isometric hip strength and risk of
      developing PFP. Moderate evidence from cross-sectional studies indicates that men
      and women with PFP have lower isometric hip musculature strength compared to pain
      free individuals. Limited evidence indicates that adolescents with PFP do not
      have the same strength deficits as adults with PFP. CONCLUSIONS: This review
      highlights a possible discrepancy between prospective and cross-sectional
      research. Cross-sectional studies indicate that adult men and women with PFP
      appear to have lower hip strength compared to pain-free individuals. Contrary to
      this, a limited number of prospective studies indicate that there may be no
      association between isometric hip strength and risk of developing PFP. Therefore,
      reduced hip strength may be a result of PFP rather than the cause.

PMID- 24687012
TI  - Evaluation of designer amphetamine interference in GC-MS amine confirmation
      procedures.
AB  - In recent years, a class of new designer drugs commonly referred to as 'bath
      salts' have made their way to the illicit drug market. The most common drugs
      encountered are designer amphetamines and cathinones. Many analytical methods for
      analysis and identification of bath salts have been published, but there has been
      little reported on their impact on existing gas chromatography-mass spectrometry
      (GC-MS) amine confirmation methods. Due to structural similarities, the potential
      exists that designer amphetamines may interfere with methods used for analysis of
      sympathomimetic amines. Methiopropamine, 4-fluoroamphetamine, 4
      fluoromethamphetamine (4-FMA) and 4-methylamphetamine were examined for potential
      interference with immunoassays and GC-MS confirmation analysis utilizing three
      derivatization procedures: R(-)-alpha-methoxy-alpha-trifluoromethylphenylacetyl
      chloride (R-MTPAC), heptafluorobutyric anhydride (HFBA) and chlorodifluoroacetic
      anhydride (ClF(2)AA). Significant cross-reactivity was observed with all the four
      compounds on the Syva Emit((r)) II Plus Amphetamines and Roche KIMS Amphetamines
      II immunoassays. Laboratories utilizing GC-MS selected-ion-monitoring
      confirmation methods with R-MTPAC, HFBA or ClF(2)AA derivatives could experience
      potential chromatographic and mass spectral interferences from 4
      fluroamphetamine, 4-FMA and methiopropamine in the form of ion ratio and
      quantitative failures. Careful ion selection, proper selectivity and specificity
      studies during method validation and rigid chromatographic and spectral
      acceptance criteria are required to assure the robustness and accuracy of GC-MS
      methods.

PMID- 24687011
TI  - High knee abduction moments are common risk factors for patellofemoral pain (PFP)
      and anterior cruciate ligament (ACL) injury in girls: is PFP itself a predictor
      for subsequent ACL injury?
AB  - BACKGROUND: Identifying risk factors for knee pain and anterior cruciate ligament
      (ACL) injury can be an important step in the injury prevention cycle. OBJECTIVE:
      We evaluated two unique prospective cohorts with similar populations and
      methodologies to compare the incidence rates and risk factors associated with
      patellofemoral pain (PFP) and ACL injury. METHODS: The 'PFP cohort' consisted of
      240 middle and high school female athletes. They were evaluated by a physician
      and underwent anthropometric assessment, strength testing and three-dimensional
      landing biomechanical analyses prior to their basketball season. 145 of these
      athletes met inclusion for surveillance of incident (new) PFP by certified
      athletic trainers during their competitive season. The 'ACL cohort' included 205
      high school female volleyball, soccer and basketball athletes who underwent the
      same anthropometric, strength and biomechanical assessment prior to their
      competitive season and were subsequently followed up for incidence of ACL injury.
      A one-way analysis of variance was used to evaluate potential group (incident PFP
      vs ACL injured) differences in anthropometrics, strength and landing
      biomechanics. Knee abduction moment (KAM) cut-scores that provided the maximal
      sensitivity and specificity for prediction of PFP or ACL injury risk were also
      compared between the cohorts. RESULTS: KAM during landing above 15.4 Nm was
      associated with a 6.8% risk to develop PFP compared to a 2.9% risk if below the
      PFP risk threshold in our sample. Likewise, a KAM above 25.3 Nm was associated
      with a 6.8% risk for subsequent ACL injury compared to a 0.4% risk if below the
      established ACL risk threshold. The ACL-injured athletes initiated landing with a
      greater knee abduction angle and a reduced hamstrings-to-quadriceps strength
      ratio relative to the incident PFP group. Also, when comparing across cohorts,
      the athletes who suffered ACL injury also had lower hamstring/quadriceps ratio
      than the players in the PFP sample (p<0.05). CONCLUSIONS: In adolescent girls
      aged 13.3 years, >15 Nm of knee abduction load during landing is associated with
      greater likelihood of developing PFP. Also, in girls aged 16.1 years who land
      with >25 Nm of knee abduction load during landing are at increased risk for both
      PFP and ACL injury.

PMID- 24687013
TI  - [Emergency psychopharmacotherapy in Hungary -- preliminary data].
AB  - OBJECTIVES: Although the number of patients admitted for psychiatric emergency
      care is increasing according to data from various countries, there are no large
      scale studies assessing clinical emergency practice and in several countries no
      national guidelines have been published concerning emergency care in psychiatry.
      The aim of our study was to assess practice related to emergency care of agitated
      psychotic patients in Hungary. METHODS: Anonymous survey questionnaire with
      questions related to care of an agitated patient showing psychotic symptoms was
      dispatched to 210 institutions providing psychiatric care in Hungary in 2013.
      RESULTS: The overwhelming majority of the 155 participating clinicians would use
      haloperidol (92.9%) and benzodiazepines (81.3%), 74.8% in a dual combination.
      18.7% would apply monotherapy and 5.2% a triple combination of medications. 59.4%
      would use i.v. and 23.9% i.m. therapy, and 9% would apply the combination of
      these two. In case of failure of first-line therapy, 76.8% of participants would
      repeat the previous medication. CONCLUSIONS: The aim of our study was to assess
      emergency interventions in psychiatry focusing on different psychopharmacological
      approaches. Our results provide a cross-sectional view on current practice in
      Hungary, and therefore may contribute to outlining practice-coherent guidelines
      and also provide the opportunity for a comparison with international trends.

PMID- 24687014
TI  - Disease activity and disability evolution under glatiramer acetate: a clinical
      approach.
AB  - INTRODUCTION: By analyzing literature data regarding glatiramer acetate in the
      treatment of relapsing-remitting multiple sclerosis one might find controversial
      data but the majority of authors state that the clinical evolution under the
      treatment showed a positive course. MATERIALS AND METHODS: Our goal was to
      analyze groups of patients, both non-treated and treated with the drug, for
      relapse rate, Kurtzke's Expanded Disability Status Scale (EDSS) score, Multiple
      Sclerosis Functional Composite (MSFC) score - upper limb disability, lower limb
      disability and cognition, and for cognitive dysfunction, using the Montreal
      Cognitive Assessment (MoCA) test, in order to objectively quantify the clinical
      impact of the drug. RESULTS/CONCLUSIONS: Our results are in accordance with the
      literature for most of the investigated measures - relapse rate, EDSS, MSFC -,
      and furthermore suggest the possibility to use more extensively the MoCA test for
      evaluation of MS patients from the point of view of cognitive functions, after a
      much wider comparative assessment.

PMID- 24687015
TI  - [Catatonia and neuroleptic malignant syndrome in view of a psychopathological and
      pathophysiological overlap: a brief review].
AB  - Catatonia was first described in the 19th century as a syndrome with motor,
      affective and behavioral symptoms. During the 20th century it was rather regarded
      as a rare motoric manifestation of schizophrenia and that classification has
      almost resulted in the disappearance of catatonia among patients outside of the
      schizophrenia spectrum. With the introduction of neuroleptics, the incidence of
      catatonic schizophrenia also declined which was attributed to effective
      treatment. Simultaneously, neuroleptic malignant syndrome was described, which
      shows many similarities with catatonia. Recently, several researchers suggested a
      common origin of the two disorders. In this paper we review case reports of the
      last five years, in which both neuroleptic malignant syndrome and catatonia had
      emerged as a diagnosis. Additionally, based on the relevant literature, we
      propose a common hypothetical pathomechanism with therapeutic implications for
      the two syndromes. Besides underlining the difficulties of differential
      diagnosis, the reviewed cases demonstrate a transition between the two illnesses.
      The similarities and the possible shifts may suggest a neuropathological and
      pathophysiological overlap in the background of the two syndromes.
      Electroconvulsive therapy and benzodiazepines seem to be an effective treatment
      in both syndromes. These two treatment approaches can be highly valuable in
      clinical practice, especially if one considers the difficulties of differential
      diagnosis. 

PMID- 24687016
TI  - The effect of negative mood and major depressive episode on working memory and
      implicit learning.
AB  - Major depressive episode (MDE) is one of the most common psychiatric diagnoses
      and it has long-term mental and physiological consequences. The status of
      cognitive functions is of specific importance in case of affective disorders, due
      to their influence not only on patients' behaviour, but to a certain extent also
      on the success of psychotherapy. In addition, examining the impact of mood and
      affective disorders on cognitive functions also helps us understand the
      relationship between brain plasticity and neurocognitive networks. While the
      relationship between explicit, conscious memory and mood are relatively well
      explored, the effect of mood and affective disorders on working memory and
      implicit sequence learning received less attention. The present review aims to
      overview available results in these less-explored areas. Research suggests that
      while working memory performance shows impairments in MDE and in some specific
      mood conditions, effects of affective disorders and mood on implicit sequence
      learning are more contradictory, highlighting the need for further studies in
      this field. 

PMID- 24687017
TI  - Lamotrigine in the treatment of psychotic depression associated with hereditary
      coproporphyria -- case report and a brief review of the literature.
AB  - OBJECTIVE: We report a successful treatment with lamotrigine of a patient with
      hereditary coproporphyria presenting with affective and psychotic symptoms. CASE
      REPORT: M.F., a 38-year-old, single woman was admitted to an acute psychiatric
      ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was
      diagnosed 9 years before the current admission. While on treatment with
      olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view
      of her significant mood fluctuations predominantly with depressed phases,
      lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually
      became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow
      up, while still on lamotrigine, her porphyria was asymptomatic. CONCLUSION: To
      the best of our knowledge, this is the first report about the safe administration
      of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute
      porphyric attack as confirmed by clinical and laboratory findings.

PMID- 24687018
TI  - The spatial hearing questionnaire: data from individuals with normal hearing.
AB  - PURPOSE: Although a number of questionnaires are available to assess hearing aid
      benefit and general hearing disability, relatively few investigate spatial
      hearing ability in more complex listening situations. The aim of this study was
      to document the performance of individuals with normal hearing using the Spatial
      Hearing Questionnaire (SHQ; Tyler, Perreau, & Ji, 2009) and to compare
      performance with published data from cochlear implant (CI) users. METHOD: Fifty
      one participants with normal hearing participated. All participants completed the
      24-item SHQ. Also, a factor analysis and reliability tests were performed.
      RESULTS: Performance on the SHQ was high (87%) for the participants with normal
      hearing. Subjective ratings varied across different listening situations:
      Understanding speech in quiet (98%) was rated higher than sound localization
      (84%) and understanding speech in a background of noise (85%). Compared with
      previously published data (Tyler, Perreau, & Ji, 2009), listeners with normal
      hearing rated their spatial hearing ability significantly better than bilateral
      and unilateral CI users. Results confirmed that the SHQ is a reliable measure of
      spatial hearing ability for listeners with normal hearing. CONCLUSIONS: Overall,
      results indicated that the SHQ is able to capture expected differences between
      individuals with normal hearing and CI users. These new data can be used as
      targets following the provision of hearing devices.

PMID- 24687019
TI  - Asthma and the flu: a tricky two-step.

PMID- 24687020
TI  - Circulating CD1c(+) DCs are superior at activating Th2 responses upon Phl p
      stimulation compared with basophils and pDCs.
AB  - The contributing role of circulating human dendritic cell (DC) populations and
      basophils in the presentation and augmentation of Th2 responses remains to be
      determined. The present study aimed at elucidating the functional role of CD1c(+)
      myeloid DCs (mDCs), CD123(+) plasmacytoid DCs (pDCs), monocyte-derived DCs and
      basophils in allergen presentation and Th2 activation. By coculturing Phleum
      pratense (Phl p)-pulsed CD1c(+) mDCs, CD123(+) pDCs, monocyte-derived DCs and
      basophils with autologous CD4(+) effector memory T cells, we assessed T-cell
      proliferation as well as the frequency of interleukin-4- and interferon-gamma
      producing T cells. Interestingly, a Th2-stimulating ability was observed for Phl
      p-challenged CD1c(+) mDCs and monocyte-derived DCs, while CD123(+) pDCs and
      basophils did not affect the Th-balance. In addition, both Phl p-pulsed CD1c(+)
      mDCs and monocyte-derived DCs stimulated increased T-cell proliferation compared
      to basophils and CD123(+) pDCs. Together, these results point to a prominent role
      for circulating CD1c(+) mDCs in allergen presentation and augmentation of Th2
      responses, making them promising therapeutic targets for Type I hypersensitivity
      reactions.

PMID- 24687022
TI  - Frontispiece.

PMID- 24687021
TI  - Activation of the NLRP3 inflammasome is not a feature of all particulate vaccine
      adjuvants.
AB  - Particulate vaccine formulations, designed to improve the delivery of antigens to
      antigen-presenting cells (APCs) and to stimulate an immune response, have been
      shown to activate the NLRP3 inflammasome. This leads to the processing and
      secretion of interleukin (IL)-1beta, which supports the recruitment of pro
      inflammatory immune cells into the tissue and can therefore be beneficial for
      vaccine potency. Recent work suggested that this may be a common mechanism of
      action for all particulate formulations. The aim of this study was to investigate
      whether the activation of the NLRP3 inflammasome was common to many delivery
      systems. We prepared polymer-based chitosan nanoparticles (CNPs), lipid-based
      cubosomes, a water in oil emulsion of incomplete Freund's adjuvant (IFA) and alum
      formulations and examined inflammasome activation in vitro using murine bone
      marrow-derived dendritic cells and human peripheral blood mononuclear cells and
      in vivo in mice. The formulations differed in their morphology, size and zeta
      potential. Only the positively charged particles (CNPs and alum) were able to
      activate the inflammasome and increase the secretion of IL-1beta. A decrease in
      the activation of the inflammasome with these particulates was observed when
      cathepsin B-mediated effects were blocked, implying a role of lysosomal rupture
      in the activation process. These findings demonstrate a role for the surface
      charge of particulates in the activation of the NLRP3 inflammasome, which should
      be considered when designing a novel vaccine formulation.

PMID- 24687024
TI  - Legislation impacting audiology and the provision of audiological services: a
      review of legislation across the United States.
AB  - PURPOSE: The purpose of this review was to investigate the legislation about the
      provision of audiology services. Specifically, the goal of the review was to
      investigate the similarities and differences in legislation regarding the
      identification of, and audiology services provided to, children with hearing
      loss. METHOD: A systematic review was conducted to collect state-specific
      legislation regarding the audiology licensure requirements, requirements about
      the identification and management of children with hearing loss, and insurance
      coverage regulations. Compiled data were analyzed for similarities and
      differences between state regulations and legislature. RESULTS: All states
      require audiologists to hold licensure; however, many differences exist between
      the requirements of acquiring and maintaining the license. Some states regulate
      the identification and management of children with hearing loss, whereas others
      do not. Additionally, states differ in their regulation of services provided to
      children with hearing loss, who can provide these services, and what is covered
      by insurance. CONCLUSION: It is critical for audiologists to understand the
      requirements of their state in the provision of audiology services. Specifically,
      it is important for audiologists to understand how the laws may impact the
      services they provide to children with hearing loss.

PMID- 24687025
TI  - Hand-assisted thoracoscopic surgery for pulmonary metastasectomy through
      sternocostal triangle access: superiority in detection of non-imaged pulmonary
      nodules.
AB  - Hand-Assisted Thoracoscopic Surgery for pulmonary metastasectomy through
      sternocostal triangle access allows manual palpation of both lungs, thus
      permitting effective treatment of lung metastases. In our research, 62 patients
      from November 2001 to January 2012 underwent our Hand-Assisted Thoracoscopic
      Surgery procedures for pulmonary metastasectomy. Clinical data, including the
      number of pulmonary metastases determined by Computed Tomography/Positron
      Emission Tomography-Computed Tomography, surgical findings and survival data of
      these patients were collected. We found that the median follow-up time was 23.7
      months (range 2.4 to 85.6 months). 30 cases of them had post-operative
      recurrences and the median disease-free survival period was 27.4 months. For
      Computed Tomography scan, the overall sensitivity for proved metastases was 63%
      (115/182). 67 non-imaged malignant nodules were palpated and removed in 14 cases.
      For Positron Emission Tomography-Computed Tomography scan, the overall
      sensitivity was 66% (79/120). 41 non-imaged malignant nodules were palpated and
      removed in 12 cases. This study show that the Hand-Assisted Thoracoscopic Surgery
      provides an easier way for routine bilateral pleural exploration, and thus is
      critical and effective in detection of non-imaged malignant pulmonary metastases,
      which might contribute to long-term disease-free survival. 

PMID- 24687026
TI  - Individual differences in language ability are related to variation in word
      recognition, not speech perception: evidence from eye movements.
AB  - PURPOSE: The authors examined speech perception deficits associated with
      individual differences in language ability, contrasting auditory, phonological,
      or lexical accounts by asking whether lexical competition is differentially
      sensitive to fine-grained acoustic variation. METHOD: Adolescents with a range of
      language abilities (N = 74, including 35 impaired) participated in an experiment
      based on McMurray, Tanenhaus, and Aslin (2002). Participants heard tokens from
      six 9-step voice onset time (VOT) continua spanning 2 words (beach/peach,
      beak/peak, etc.) while viewing a screen containing pictures of those words and 2
      unrelated objects. Participants selected the referent while eye movements to each
      picture were monitored as a measure of lexical activation. Fixations were
      examined as a function of both VOT and language ability. RESULTS: Eye movements
      were sensitive to within-category VOT differences: As VOT approached the
      boundary, listeners made more fixations to the competing word. This did not
      interact with language ability, suggesting that language impairment is not
      associated with differential auditory sensitivity or phonetic categorization.
      Listeners with poorer language skills showed heightened competitors fixations
      overall, suggesting a deficit in lexical processes. CONCLUSION: Language
      impairment may be better characterized by a deficit in lexical competition
      (inability to suppress competing words), rather than differences in phonological
      categorization or auditory abilities.

PMID- 24687027
TI  - Lexical characteristics of expressive vocabulary in toddlers with autism spectrum
      disorder.
AB  - PURPOSE: Vocabulary is a domain of particular challenge for many children with
      autism spectrum disorder (ASD). Recent research has drawn attention to ways in
      which lexical characteristics relate to vocabulary acquisition. The current study
      tested the hypothesis that lexical characteristics account for variability in
      vocabulary size of young children with ASD, applying the extended statistical
      learning theory of vocabulary delay in late talkers (Stokes, Kern, & Dos Santos,
      2012) to toddlers with ASD. METHOD: Parents reported the words produced by
      toddlers with ASD (n = 57; age 21-37 months) or toddlers without ASD (n = 41; age
      22-26 months) on the MacArthur-Bates Communicative Development Inventories. The
      average phonological neighborhood density, word frequency, and word length of
      each toddler's lexicon were calculated. These lexical characteristics served as
      predictors of vocabulary size. RESULTS: Findings differed for toddlers with and
      without ASD and according to subsamples. Word length was the most consistent
      predictor of vocabulary size for toddlers with ASD. CONCLUSIONS: Distinct
      relationships between lexical characteristics and vocabulary size were observed
      for toddlers with and without ASD. Experimental studies on distributional cues to
      vocabulary acquisition are needed to inform what is known about mechanisms of
      learning in neurodevelopmental disorders.

PMID- 24687028
TI  - Expression of HLA class I antigen, aspirin use, and survival after a diagnosis of
      colon cancer.
AB  - IMPORTANCE: Use of aspirin (which inhibits platelet function) after a colon
      cancer diagnosis is associated with improved overall survival. Identifying
      predictive biomarkers of this effect could individualize therapy and decrease
      toxic effects. OBJECTIVE: To demonstrate that survival benefit associated with
      low-dose aspirin use after a diagnosis of colorectal cancer might depend on HLA
      class I antigen expression. DESIGN, SETTING, AND PARTICIPANTS: A cohort study
      with tumor blocks from 999 patients with colon cancer (surgically resected
      between 2002 and 2008), analyzed for HLA class I antigen and prostaglandin
      endoperoxide synthase 2 (PTGS2) expression using a tissue microarray. Mutation
      analysis of PIK3CA was also performed. Data on aspirin use after diagnosis were
      obtained from a prescription database. Parametric survival models with
      exponential (Poisson) distribution were used to model the survival. MAIN OUTCOMES
      AND MEASURES: Overall survival. RESULTS: The overall survival benefit associated
      with aspirin use after a diagnosis of colon cancer had an adjusted rate ratio
      (RR) of 0.53 (95% CI, 0.38-0.74; P < .001) when tumors expressed HLA class I
      antigen compared with an RR of 1.03 (0.66-1.61; P = .91) when HLA antigen
      expression was lost. The benefit of aspirin was similar for tumors with strong
      PTGS2 expression (0.68; 0.48-0.97; P = .03), weak PTGS2 expression (0.59; 0.38
      0.97; P = .02), and wild-type PIK3CA tumors (0.55; 0.40-0.75; P < .001). No
      association was observed with mutated PIK3CA tumors (0.73; 0.33-1.63; P = .44).
      CONCLUSIONS AND RELEVANCE: Contrary to the original hypothesis, aspirin use after
      colon cancer diagnosis was associated with improved survival if tumors expressed
      HLA class I antigen. Increased PTGS2 expression or the presence of mutated PIK3CA
      did not predict benefit from aspirin. HLA class I antigen might serve as a
      predictive biomarker for adjuvant aspirin therapy in colon cancer.

PMID- 24687029
TI  - A brief history of USNCB: motivation and formation.

PMID- 24687030
TI  - Immigration within the United States: prevalence of childhood hearing loss
      revisited.
AB  - PURPOSE: As more adult and child immigrants enter the United States each year,
      there is a high likelihood that the prevalence of childhood hearing loss in the
      United States is underestimated, given estimations of the number of immigrant
      children entering the country with hearing loss. METHOD: Information was
      collected using online search engines and peer-reviewed journals. The most recent
      articles available through search engines included in EBSCOhost at the time were
      used. The gathered data were organized by emigrating country, and the 2 countries
      with the highest immigration rates were presented. Estimations of the number of
      children immigrating with hearing loss were made using data from published peer
      reviewed articles and government reports on immigration. CONCLUSIONS: The
      prevalence of hearing loss in the United States is underestimated when
      considering undetected hearing loss in immigrant children. The addition of the
      immigrant children from only Mexico and China presents a 7.5% increase in the
      total number of children in the United States with hearing loss. This reinforces
      the importance of early detection of hearing loss in these children, resulting in
      more accurate estimation of the rate of childhood hearing loss in the United
      States and better planning for intervention programs.

PMID- 24687031
TI  - Cognitive-perceptual examination of remediation approaches to hypokinetic
      dysarthria.
AB  - PURPOSE: To determine how increased vocal loudness and reduced speech rate affect
      listeners' cognitive-perceptual processing of hypokinetic dysarthric speech
      associated with Parkinson's disease. METHOD: Fifty-one healthy listener
      participants completed a speech perception experiment. Listeners repeated phrases
      produced by 5 individuals with dysarthria across habitual, loud, and slow
      speaking modes. Listeners were allocated to habitual ( n = 17), loud ( n = 17),
      or slow ( n = 17) experimental conditions. Transcripts derived from the phrase
      repetition task were coded for overall accuracy (i.e., intelligibility), and
      perceptual error analyses examined how these conditions affected listeners'
      phonemic mapping (i.e., syllable resemblance) and lexical segmentation (i.e.,
      lexical boundary error analysis). RESULTS: Both speech conditions provided
      obvious perceptual benefits to listeners. Overall, transcript accuracy was
      highest in the slow condition. In the loud condition, however, improvement was
      evidenced across the experiment. An error analysis suggested that listeners in
      the loud condition prioritized acoustic-phonetic cues in their attempts to
      resolve the degraded signal, whereas those in the slow condition appeared to
      preferentially weight lexical stress cues. CONCLUSIONS: Increased loudness and
      reduced rate exhibited differential effects on listeners' perceptual processing
      of dysarthric speech. The current study highlights the insights that may be
      gained from a cognitive-perceptual approach.

PMID- 24687032
TI  - Prostate cancer: muddying the waters by overlooking treatment modality.

PMID- 24687033
TI  - Prostate cancer: a new look at prostate cancer treatment complications.

PMID- 24687034
TI  - Gynaecological cancer: AURELIA--ovarian combination.

PMID- 24687035
TI  - Implementing personalized cancer care.
AB  - Implementing personalized cancer care requires a sound understanding of cancer
      genomics, familiarity with the analytical methods used to study cancer, knowledge
      of the mechanisms of action of targeted drugs, and ways to assimilate and
      understand complex data sets. Perhaps the greatest challenge is obtaining the
      drugs predicted to be beneficial based on the genomic profile of a patient's
      tumour. A potential solution is creation of a national facilitated access
      programme and registry for off-label use of targeted anti-cancer drugs. Within
      such a programme, patients could receive the targeted agent matched to the
      genomic profile of their tumour. Physicians would receive guidance in
      interpretation of complex genomic tests and access to drugs. Pharmaceutical
      companies, payers and regulators would receive data on off-label drug and test
      use and clinical outcomes to inform their research and development plans and
      coverage decisions and to track real-world safety. Although recently launched
      prospective clinical trials will determine the true benefit of matching drugs to
      genomic alterations, the approach proposed here will facilitate delivery of
      personalized medicine services to participating patients while at the same time
      making observations that allow us to learn from each patient to inform clinical
      care and future research initiatives.

PMID- 24687036
TI  - Effect of surface carbon coating on sintering of silver nanoparticles: in situ
      TEM observations.
AB  - In this work, in situ transmission electron microscopy heating has been used to
      investigate the effects of a carbon capping layer on sintering of silver
      nanoparticles. For the first time, we make direct and real-time measurements of
      surface diffusivity of silver in nanoparticles coated with carbon. We observe
      that the carbon surface coatings may significantly inhibit sintering in silver
      nanoparticles. 

PMID- 24687037
TI  - Experiences of physical activity: A phenomenological study of individuals with
      cystic fibrosis.
AB  - Although extensive research has investigated the benefits of physical activity in
      cystic fibrosis, minimal exploration of the experiences for individuals from a
      qualitative, phenomenological perspective has been carried out. The aim of this
      study was to explore the subjective experiences of physical activity for
      individuals with cystic fibrosis. The health-care team, at an Adult Cystic
      Fibrosis Unit in the United Kingdom, recruited 12 participants to take part.
      Interview data were analysed using interpretative phenomenological analysis. A
      central theme of 'self-monitoring' emerged from the accounts and was embedded in
      the three super-ordinate themes. 

PMID- 24687039
TI  - Direct evidence of plasmon enhancement on photocatalytic hydrogen generation over
      Au/Pt-decorated TiO2 nanofibers.
AB  - Direct evidence of plasmon-enhanced H2 generation is observed in photocatalytic
      water reduction by using TiO2 electrospun nanofibers co-decorated with Au and Pt
      nanoparticles through dual-beam irradiation. The Au/Pt/TiO2 nanofibers exhibit
      certain activity for H2 generation under single irradiation at 420 nm that
      excites the defect/impurity states of TiO2. Significantly, when secondary
      irradiation at 550 nm is introduced to simultaneously excite Au SPR, we observed
      2.5 times higher activity for H2 generation. Further investigation by finely
      controlling the irradiation wavelengths reveals that the enhancement factor on
      the photocatalytic activity for H2 generation is directly correlated with the
      plasmon absorption band of the Au nanoparticles in the Au/Pt/TiO2 nanofibers. The
      control experiments with different sacrificial agents suggest that the hot
      plasmonic electrons of Au are responsible for the enhanced photocatalytic
      activity that can be magnified when TiO2 is simultaneously excited. 

PMID- 24687038
TI  - The protective effect of topical rifamycin treatment against sternal wound
      infection in diabetic patients undergoing on-pump coronary artery bypass graft
      surgery.
AB  - OBJECTIVES: The aim of this study was to investigate the protective effect of
      topical rifamycin SV treatment against sternal wound infection (SWI) in diabetic
      patients undergoing on-pump coronary artery bypass graft (CABG) surgery. METHODS:
      One hundred and fifty-nine diabetic patients who were scheduled to undergo
      isolated on-pump CABG surgery were included. Eight were excluded for various
      reasons. Of the 151 patients, 51 were on insulin therapy and 100 were on oral
      anti-diabetics. The risk of mediastinitis was assessed using the American College
      of Cardiology/American Heart Association 2004 guideline update for CABG surgery.
      According to the risk scores, patients were divided into two comparable groups:
      the rifamycin group (n = 78) received topical rifamycin treatment after on-pump
      CABG surgery, and the control group (n = 73) received no topical treatment.
      RESULTS: Deep sternal wound infection (mediastinitis) was not observed in either
      group (0/78 vs 0/73, p = 1.0). No superficial sternal wound infection was
      observed in the rifamycin group, however, it did occur in one patient in the
      control group (0/78 vs 1/73, p = 0.303). Wound culture was performed and
      coagulase-negative staphylococci were observed. The infection regressed on
      initiation of antibiotic therapy against isolated bacteria and the patient was
      discharged after a full recovery. CONCLUSIONS: Although the difference in rate of
      superficial sternal wound infection (SSWI) in the rifamycin and control groups
      was not statistically significant, locally applied rifamycin SV during closure of
      the sternum in the CABG operation may have had a protective affect against SWI.

PMID- 24687041
TI  - X-linked hearing loss: two gene mutation examples provide generalizable
      implications for clinical care.
AB  - PURPOSE: To describe the inheritance patterns and auditory phenotype features of
      3 Canadian families with mutations in 2 X-linked "deafness" genes (DFNX). METHOD:
      Audiological, medical, and family histories were collected and family members
      interviewed to compare hearing thresholds and case histories between cases with
      mutations in SMPX versus POU3F4. RESULTS: The family pedigrees reveal
      characteristic X-linked inheritance patterns. Phenotypic features associated with
      the SMPX (DFNX4) mutation include early onset in males with rapid progression
      from mild and flat to sloping sensorineural loss, with highly variable onset and
      hearing loss severity in females. In contrast, phenotypic features associated
      with the POU3F4 (DFNX2) mutation are characterized by an early onset, mixed
      hearing loss with fluctuation in males, and a normal hearing phenotype reported
      for females. CONCLUSIONS: The study shows how this unique inheritance pattern and
      both gender and mutation-specific phenotype variations can alert audiologists to
      the presence of X-linked genetic etiologies in their clinical practice. By
      incorporating this knowledge into clinical decision making, audiologists can
      facilitate the early identification of X-linked hearing loss and contribute to
      the effective team management of affected families.

PMID- 24687040
TI  - Low yield of stress imaging in a population-based study of asymptomatic patients
      after percutaneous coronary intervention.
AB  - BACKGROUND: Little is known about the clinical value of stress imaging studies in
      asymptomatic patients after percutaneous coronary intervention (PCI). METHODS AND
      RESULTS: Residents of Olmsted County, MN, who underwent PCI were followed up for
      the occurrence of stress imaging (stress nuclear or stress echocardiography),
      coronary angiography, or coronary artery bypass grafting (without angiography) as
      initial procedures after PCI. Patients whose first follow-up procedure was a
      stress imaging test were evaluated for their symptom status at the time of the
      study and whether they underwent angiography or revascularization (PCI or
      coronary artery bypass grafting) within 90 days. Of 1848 patients who underwent
      PCI during the study period, 710 (38%) had stress imaging as their initial
      procedure after PCI, and 241 (13% of the entire cohort) were asymptomatic at the
      time of testing. The majority (86%) of these 241 patients underwent PCI for acute
      myocardial infarction or unstable angina. Within 90 days of stress imaging, 16 of
      the 241 asymptomatic patients underwent angiography, and 2 patients were
      revascularized. Stratified by timing after PCI, none of 138 asymptomatic patients
      tested within 2 years of PCI underwent revascularization. Two of 103 asymptomatic
      patients tested after 2 years from PCI underwent revascularization. Compared with
      patients who were asymptomatic at the time of stress imaging, patients who did
      not undergo any follow-up procedures (stress imaging, angiography, or coronary
      artery bypass grafting) after the index PCI were older, were more likely to have
      comorbidities, and had significantly greater all-cause mortality (P<0.001).
      CONCLUSIONS: In a population-based sample of patients undergoing PCI primarily
      for acute coronary syndromes, 1 in 8 had subsequent stress imaging when they were
      asymptomatic. These stress imaging tests resulted in further revascularization in
      <1% of patients. The low rate of downstream revascularization suggests that
      stress imaging in asymptomatic patients after PCI has low value.

PMID- 24687043
TI  - Pronoun comprehension in individuals with down syndrome: deviance or delay?
AB  - PURPOSE: Results of recent pilot studies suggest that the interpretation of
      pronouns in individuals with Down syndrome (DS) may follow a pattern unattested
      in typical development, indicating the presence of a selective deficit targeting
      the comprehension of reflexive pronouns. These findings come at a time when there
      is a heated debate surrounding pronoun comprehension in typical development as
      well. This study aims to contribute to these debates by examining pronoun
      comprehension in Greek, a language that exhibits unusual patterns in pronoun
      comprehension in typical development. METHOD: Seven Greek-speaking individuals
      with DS and a control group of 14 typically developing (TD) children were tested.
      The authors examined the comprehension of strong pronouns, reflexive pronouns,
      and pronominal clitics, using a picture selection task. RESULTS: The data reveal
      evidence of deviant pronoun comprehension in individuals with DS compared with
      the TD group. The DS group encountered problems in the interpretation of
      reflexive pronouns when compared with the TD group, while the performance of the
      two groups was comparable in all remaining conditions. CONCLUSIONS: Findings are
      in line with the selective deficit model of language comprehension in DS,
      supporting the presence of a cross-linguistic reflexive deficit.

PMID- 24687042
TI  - Impact of clear, loud, and slow speech on scaled intelligibility and speech
      severity in Parkinson's disease and multiple sclerosis.
AB  - PURPOSE: The perceptual consequences of rate reduction, increased vocal
      intensity, and clear speech were studied in speakers with multiple sclerosis
      (MS), Parkinson's disease (PD), and healthy controls. METHOD: Seventy-eight
      speakers read sentences in habitual, clear, loud, and slow conditions. Sentences
      were equated for peak amplitude and mixed with multitalker babble for
      presentation to listeners. Using a computerized visual analog scale, listeners
      judged intelligibility or speech severity as operationally defined in Sussman and
      Tjaden (2012). RESULTS: Loud and clear but not slow conditions improved
      intelligibility relative to the habitual condition. With the exception of the
      loud condition for the PD group, speech severity did not improve above habitual
      and was reduced relative to habitual in some instances. Intelligibility and
      speech severity were strongly related, but relationships for disordered speakers
      were weaker in clear and slow conditions versus habitual. CONCLUSIONS: Both clear
      and loud speech show promise for improving intelligibility and maintaining or
      improving speech severity in multitalker babble for speakers with mild dysarthria
      secondary to MS or PD, at least as these perceptual constructs were defined and
      measured in this study. Although scaled intelligibility and speech severity
      overlap, the metrics further appear to have some separate value in documenting
      treatment-related speech changes.

PMID- 24687044
TI  - Optimization of human immunodeficiency virus treatment during incarceration:
      viral suppression at the prison gate.
AB  - IMPORTANCE: Human immunodeficiency virus (HIV) management in correctional
      settings is logistically feasible, but HIV-related outcomes before release have
      not been recently systematically examined. OBJECTIVE: To evaluate HIV treatment
      outcomes throughout incarceration, including jail and prison. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective cohort study of longitudinally linked
      demographic, pharmacy, and laboratory data on 882 prisoners within the
      Connecticut Department of Correction (2005-2012) with confirmed HIV infection,
      who were continually incarcerated 90 days or more, had at least 2 HIV-1 RNA and
      CD4 lymphocyte measurements, and were prescribed antiretroviral therapy. MAIN
      OUTCOMES AND MEASURES: Three electronic databases (correctional, laboratory, and
      pharmacy) were integrated to assess HIV viral suppression (HIV-1 RNA levels, <400
      copies/mL) on intake and release. Secondary outcomes were mean change in log
      transformed HIV-1 RNA levels and mean change in CD4 lymphocyte count during
      incarceration. Demographic characteristics, prescribed pharmacotherapies, receipt
      of directly observed therapy, and duration of incarceration were analyzed as
      possible explanatory variables for HIV viral suppression in logistic regression
      models. RESULTS: Among 882 HIV-infected prisoners with 1185 incarceration
      periods, mean HIV-1 RNA level decreased by 1.1 log10 and CD4 lymphocyte count
      increased by 98 cells/uL over time, with a higher proportion achieving viral
      suppression by release compared with entry (70.0% vs 29.8%; P < .001); 36.9% of
      antiretroviral therapy (ART) regimens were changed during incarceration. After
      adjusting for baseline HIV-1 RNA level, prerelease viral suppression correlated
      with female sex (adjusted odds ratio, 1.81; 95% CI, 1.26-2.59) and psychiatric
      disorder severity below the sample median (adjusted odds ratio, 1.50; 95% CI,
      1.12-1.99), but not race/ethnicity, incarceration duration, ART regimen or dosing
      strategy, or directly observed therapy. CONCLUSIONS AND RELEVANCE: Though just
      one-third of HIV-infected prisoners receiving ART entered correctional facilities
      with viral suppression, HIV treatment was optimized during incarceration,
      resulting in the majority achieving viral suppression by release. Treatment for
      HIV within prison is facilitated by a highly structured environment and, when
      combined with simple well-tolerated ART regimens, can result in viral suppression
      during incarceration. In the absence of important and effective community-based
      resources, incarceration can be an opportunity of last resort to initiate
      continuous ART for individual health and, following the "treatment as prevention"
      paradigm, potentially reduce the likelihood of HIV transmission to others after
      release if continuity of HIV care is sustained.

PMID- 24687045
TI  - Distinguishing between schizophrenia and other psychotic disorders.
AB  - The Diagnostic and Statistical Manual of Mental Disorders (DSM) has provided
      diagnostic reliability across observers while neglecting biological validity. The
      current theme issue explores the boundaries between schizophrenia and bipolar
      disorder, using neuro-cognition, systems neuroscience, and genetics as points of
      departure to begin consideration of a biologically based reclassification of
      these illnesses. 

PMID- 24687047
TI  - New route toward building active ruthenium nanoparticles on ordered mesoporous
      carbons with extremely high stability.
AB  - Creating highly active and stable metal catalysts is a persistent goal in the
      field of heterogeneous catalysis. However, a real catalyst can rarely achieve
      both of these qualities simultaneously due to limitations in the design of the
      active site and support. One method to circumvent this problem is to fabricate
      firmly attached metal species onto the voids of a mesoporous support formed
      simultaneously. In this study, we developed a new type of ruthenium catalyst that
      was firmly confined by ordered mesoporous carbons through the fabrication of a
      cubic Ia3d chitosan-ruthenium-silica mesophase before pyrolysis and silica
      removal. This facile method generates fine ruthenium nanoparticles (ca. 1.7 nm)
      that are homogeneously dispersed on a mesoporous carbonaceous framework. This
      ruthenium catalyst can be recycled 22 times without any loss of reactivity,
      showing the highest stability of any metal catalysts; this catalyst displays a
      high activity (23.3 mol(LA)h(-1)g(metal)(-1)) during the catalytic hydrogenation
      of levulinic acid (LA) when the metal loading is 6.1 wt%. Even at an ultralow
      loading (0.3 wt%), this catalyst still outperforms the most active known Ru/C
      catalyst. This work reveals new possibilities for designing and fabricating
      highly stable and active metal catalysts by creating metal sites and mesoporous
      supports simultaneously.

PMID- 24687046
TI  - Impaired metabolic reactivity to oxidative stress in early psychosis patients.
AB  - Because increasing evidence point to the convergence of environmental and genetic
      risk factors to drive redox dysregulation in schizophrenia, we aim to clarify
      whether the metabolic anomalies associated with early psychosis reflect an
      adaptation to oxidative stress. Metabolomic profiling was performed to
      characterize the response to oxidative stress in fibroblasts from control
      individuals (n = 20) and early psychosis patients (n = 30), and in all, 282
      metabolites were identified. In addition to the expected redox/antioxidant
      response, oxidative stress induced a decrease of lysolipid levels in fibroblasts
      from healthy controls that were largely muted in fibroblasts from patients. Most
      notably, fibroblasts from patients showed disrupted extracellular matrix- and
      arginine-related metabolism after oxidative stress, indicating impairments beyond
      the redox system. Plasma membrane and extracellular matrix, 2 regulators of
      neuronal activity and plasticity, appeared as particularly susceptible to
      oxidative stress and thus provide novel mechanistic insights for
      pathophysiological understanding of early stages of psychosis. Statistically,
      antipsychotic medication at the time of biopsy was not accounting for these
      anomalies in the metabolism of patients' fibroblasts, indicating that they might
      be intrinsic to the disease. Although these results are preliminary and should be
      confirmed in a larger group of patients, they nevertheless indicate that the
      metabolic signature of reactivity to oxidative stress may provide reliable early
      markers of psychosis. Developing protective measures aimed at normalizing the
      disrupted pathways should prevent the pathological consequences of environmental
      stressors. 

PMID- 24687048
TI  - Renal tissue thawed for 30 minutes is still suitable for gene expression
      analysis.
AB  - Some biosamples obtained from biobanks may go through thawing before processing.
      We aim to evaluate the effects of thawing at room temperature for different time
      periods on gene expression analysis. A time course study with four time points
      was conducted to investigate the expression profiling on 10 thawed normal mice
      renal tissue samples through Affymetrix GeneChip mouse gene 2.0 st array.
      Microarray results were validated by quantitative real time polymerase chain
      reactions (qPCR) on 6 candidate reference genes and 11 target genes.
      Additionally, we used geNorm plus and NormFinder to identify the most stably
      expressed reference genes over time. The results showed RNA degraded more after
      longer incubation at room temperature. However, microarray results showed only
      240 genes (0.91%) altered significantly in response to thawing at room
      temperature. The signal of majority altered probe sets decreased with thawing
      time, and the crossing point (Cp) values of all candidate reference genes
      correlated positively with the thawing time (p<0.05). The combination of B2M,
      ACTB and PPIA was identified as the best choice for qPCR normalization. We found
      most target genes were stable by using this normalization method. However,
      serious gene quantification errors were resulted from improper reference genes.
      In conclusion, thirty minutes of thawing at room temperature has a limited impact
      on microarray and qPCR analysis, gene expression variations due to RNA
      degradation in early period after thawing can be largely reduced by proper
      normalization. 

PMID- 24687050
TI  - Integrative knowledge management to enhance pharmaceutical R&D.
AB  - Information technologies already have a key role in pharmaceutical research and
      development (R&D), but achieving substantial advances in their use and
      effectiveness will depend on overcoming current challenges in sharing,
      integrating and jointly analysing the range of data generated at different stages
      of the R&D process.

PMID- 24687049
TI  - Sentence comprehension in boys with autism spectrum disorder.
AB  - PURPOSE: Previous research has suggested that language comprehension might be
      particularly impaired in children with autism spectrum disorder (ASD), but this
      profile has been only broadly characterized. In the current study, the authors
      examined sentence comprehension in school-age boys with ASD, including a subgroup
      with intellectual disability (ID), with particular attention paid to errors that
      might differentiate between lexically and syntactically based difficulties.
      METHOD: Participants were boys with ASD (n = 45, ages 4-11 years) and younger
      typically developing boys (n = 45, ages 2-6 years). Comprehension was assessed
      with the Test for Reception of Grammar-Version 2 (TROG-2; Bishop, 2003). Error
      types were analyzed for a subset of items. RESULTS: Boys with ASD did not differ
      from younger typically developing boys matched on receptive vocabulary in overall
      sentence comprehension on the TROG-2 or the number of lexical errors committed.
      In contrast, the subgroup of boys with ASD and ID (n = 16) had poorer overall
      performance and committed more lexical errors than younger typically developing
      boys matched on nonverbal cognition. CONCLUSIONS: On average, comprehension was
      delayed in school-age boys with ASD but not beyond receptive vocabulary
      expectations. Boys with ASD and ID, however, had a weakness in sentence
      comprehension beyond nonverbal cognitive expectations.

PMID- 24687051
TI  - Drug makers and NIH team up to find and validate targets.

PMID- 24687052
TI  - Schizophrenia drug gets negative results for negative symptoms.

PMID- 24687057
TI  - US Patent Office issues guidelines on natural product patent eligibility.

PMID- 24687059
TI  - An audience with ... Wolfgang Plischke.

PMID- 24687060
TI  - Thrombotic disorders: Seeking out better anticoagulants.

PMID- 24687061
TI  - Cancer: Unleashing NK cell anti-metastatic activity.

PMID- 24687067
TI  - The incidence and determinants of primary nonadherence with prescribed medication
      in primary care: a cohort study.
AB  - BACKGROUND: Primary nonadherence is probably an important contributor to
      suboptimal disease management, but methodological challenges have limited
      investigation of it. OBJECTIVE: To estimate the incidence of primary nonadherence
      in primary care and the drug, patient, and physician characteristics that are
      associated with nonadherence. DESIGN: A prospective cohort of patients and all
      their incident prescriptions from primary care electronic health records between
      2006 and 2009 linked to provincial drug insurer data on all drugs dispensed from
      community-based pharmacies were assembled. SETTING: Quebec, Canada. PATIENTS: 15
      961 patients in a primary care network of 131 physicians. MEASUREMENTS: Primary
      nonadherence was defined as not filling an incident prescription within 9 months.
      Multivariate alternating logistic regression was used to estimate predictors of
      nonadherence and account for patient and physician clustering. RESULTS: Overall,
      31.3% of the 37 506 incident prescriptions written for the 15 961 patients were
      not filled. Drugs in the upper quartile of cost were least likely to be filled
      (odds ratio [OR], 1.11 [95% CI, 1.07 to 1.17]), as were skin agents,
      gastrointestinal drugs, and autonomic drugs, compared with anti-infectives.
      Reduced odds of nonadherence were associated with increasing patient age (OR per
      10 years, 0.89 [CI, 0.85 to 0.92]), elimination of prescription copayments for
      low-income groups (OR, 0.37 [CI, 0.32 to 0.41]), and a greater proportion of all
      physician visits with the prescribing physician (OR per 0.5 increase, 0.77 [CI,
      0.70 to 0.85]). LIMITATION: Patients' rationale for choosing not to fill their
      prescriptions could not be measured. CONCLUSION: Primary nonadherence is common
      and may be reduced by lower drug costs and copayments, as well as increased
      follow-up care with prescribing physicians for patients with chronic conditions.
      PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

PMID- 24687068
TI  - Safety and feasibility of a diagnostic algorithm combining clinical probability,
      d-dimer testing, and ultrasonography for suspected upper extremity deep venous
      thrombosis: a prospective management study.
AB  - BACKGROUND: Although well-established for suspected lower limb deep venous
      thrombosis, an algorithm combining a clinical decision score, d-dimer testing,
      and ultrasonography has not been evaluated for suspected upper extremity deep
      venous thrombosis (UEDVT). OBJECTIVE: To assess the safety and feasibility of a
      new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN:
      Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16
      hospitals in Europe and the United States. PATIENTS: 406 inpatients and
      outpatients with suspected UEDVT. MEASUREMENTS: The algorithm consisted of the
      sequential application of a clinical decision score, d-dimer testing, and
      ultrasonography. Patients were first categorized as likely or unlikely to have
      UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was
      excluded. All other patients had (repeated) compression ultrasonography. The
      primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary
      embolism in patients with a normal diagnostic work-up. RESULTS: The algorithm was
      feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an
      unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial
      venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients,
      respectively. All 249 patients with a normal diagnostic work-up, including those
      with protocol violations (n = 16), were followed for 3 months. One patient
      developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI,
      0.0% to 2.2%). LIMITATIONS: This study was not powered to show the safety of the
      substrategies. d-Dimer testing was done locally. CONCLUSION: The combination of a
      clinical decision score, d-dimer testing, and ultrasonography can safely and
      effectively exclude UEDVT. If confirmed by other studies, this algorithm has
      potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE:
      None.

PMID- 24687066
TI  - Advances in targeting cyclic nucleotide phosphodiesterases.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP
      and cyclic GMP, thereby regulating the intracellular concentrations of these
      cyclic nucleotides, their signalling pathways and, consequently, myriad
      biological responses in health and disease. Currently, a small number of PDE
      inhibitors are used clinically for treating the pathophysiological dysregulation
      of cyclic nucleotide signalling in several disorders, including erectile
      dysfunction, pulmonary hypertension, acute refractory cardiac failure,
      intermittent claudication and chronic obstructive pulmonary disease. However,
      pharmaceutical interest in PDEs has been reignited by the increasing
      understanding of the roles of individual PDEs in regulating the subcellular
      compartmentalization of specific cyclic nucleotide signalling pathways, by the
      structure-based design of novel specific inhibitors and by the development of
      more sophisticated strategies to target individual PDE variants. 

PMID- 24687069
TI  - Associations between HIV infection and subclinical coronary atherosclerosis.
AB  - BACKGROUND: Coronary artery disease (CAD) has been associated with HIV infection,
      but data are not consistent. OBJECTIVE: To determine whether HIV-infected men
      have more coronary atherosclerosis than uninfected men. DESIGN: Cross-sectional
      study. SETTING: Multicenter AIDS Cohort Study. PARTICIPANTS: HIV-infected (n =
      618) and uninfected (n = 383) men who have sex with men who were aged 40 to 70
      years, weighed less than 136 kg (200 lb), and had no history of coronary
      revascularization. MEASUREMENTS: Presence and extent of coronary artery calcium
      (CAC) on noncontrast cardiac computed tomography (CT) and of any plaque;
      noncalcified, mixed, or calcified plaque; or stenosis on coronary CT angiography.
      RESULTS: 1001 men had noncontrast CT, of whom 759 had coronary CT angiography.
      After adjustment for age, race, CT scanning center, and cohort, HIV-infected men
      had a greater prevalence of CAC (prevalence ratio [PR], 1.21 [95% CI, 1.08 to
      1.35]; P = 0.001) and any plaque (PR, 1.14 [CI, 1.05 to 1.24]; P = 0.001),
      including noncalcified (PR, 1.28 [CI, 1.13 to 1.45]; P < 0.001) and mixed (PR,
      1.35 [CI, 1.10 to 1.65]; P = 0.004) plaque, than uninfected men. Associations
      between HIV infection and any plaque or noncalcified plaque remained significant
      (P < 0.005) after CAD risk factor adjustment. HIV-infected men had a greater
      extent of noncalcified plaque after CAD risk factor adjustment (P = 0.026). They
      also had a greater prevalence of coronary artery stenosis greater than 50% (PR,
      1.48 [CI, 1.06 to 2.07]; P = 0.020), but not after CAD risk factor adjustment.
      Longer duration of highly active antiretroviral therapy (PR, 1.09 [CI, 1.02 to
      1.17]; P = 0.007) and lower nadir CD4+ T-cell count (PR, 0.80 [CI, 0.69 to 0.94];
      P = 0.005) were associated with coronary stenosis greater than 50%. LIMITATION:
      Cross-sectional observational study design and inclusion of only men. CONCLUSION:
      Coronary artery plaque, especially noncalcified plaque, is more prevalent and
      extensive in HIV-infected men, independent of CAD risk factors. PRIMARY FUNDING
      SOURCE: National Heart, Lung, and Blood Institute and National Institute of
      Allergy and Infectious Diseases.

PMID- 24687070
TI  - Reporting discrepancies between the ClinicalTrials.gov results database and peer
      reviewed publications.
AB  - BACKGROUND: ClinicalTrials.gov requires reporting of result summaries for many
      drug and device trials. PURPOSE: To evaluate the consistency of reporting of
      trials that are registered in the ClinicalTrials.gov results database and
      published in the literature. DATA SOURCES: ClinicalTrials.gov results database
      and matched publications identified through ClinicalTrials.gov and a manual
      search of 2 electronic databases. STUDY SELECTION: 10% random sample of phase 3
      or 4 trials with results in the ClinicalTrials.gov results database, completed
      before 1 January 2009, with 2 or more groups. DATA EXTRACTION: One reviewer
      extracted data about trial design and results from the results database and
      matching publications. A subsample was independently verified. DATA SYNTHESIS: Of
      110 trials with results, most were industry-sponsored, parallel-design drug
      studies. The most common inconsistency was the number of secondary outcome
      measures reported (80%). Sixteen trials (15%) reported the primary outcome
      description inconsistently, and 22 (20%) reported the primary outcome value
      inconsistently. Thirty-eight trials inconsistently reported the number of
      individuals with a serious adverse event (SAE); of these, 33 (87%) reported more
      SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in
      ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero
      or not occurring, and 21 reported a different number of SAEs. Among 29 trials
      that reported deaths in ClinicalTrials.gov, 28% differed from the matched
      publication. LIMITATION: Small sample that included earliest results posted to
      the database. CONCLUSION: Reporting discrepancies between the ClinicalTrials.gov
      results database and matching publications are common. Which source contains the
      more accurate account of results is unclear, although ClinicalTrials.gov may
      provide a more comprehensive description of adverse events than the publication.
      PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 24687073
TI  - HIV and atherosclerosis: moving from associations to mechanisms and
      interventions.

PMID- 24687074
TI  - Metabolically healthy overweight and obesity.

PMID- 24687075
TI  - Metabolically healthy overweight and obesity.

PMID- 24687076
TI  - Metabolically healthy overweight and obesity.

PMID- 24687077
TI  - Metabolically healthy overweight and obesity.

PMID- 24687078
TI  - Metabolically healthy overweight and obesity.

PMID- 24687079
TI  - Metabolically healthy overweight and obesity.

PMID- 24687080
TI  - Metabolically healthy overweight and obesity.

PMID- 24687081
TI  - Feasibility and cost-effectiveness of stroke prevention through community
      screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF
      study.
AB  - Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected
      before stroke. Identification of unknown AF in the community and subsequent anti
      thrombotic treatment could reduce stroke burden. We investigated community
      screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies,
      and determined the cost-effectiveness of this strategy.Pharmacists performedpulse
      palpation and iECG recordings, with cardiologist iECG over-reading. General
      practitioner review/12-lead ECG was facilitated for suspected new AF. An
      automated AF algorithm was retrospectively applied to collected iECGs. Cost
      effectiveness analysis incorporated costs of iECG screening, and
      treatment/outcome data from a United Kingdom cohort of 5,555 patients with
      incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged
      >=65 years (mean 76 +/- 7 years; 44% male) were screened. Newly identified AF was
      found in 1.5% (95% CI, 0.8-2.5%); mean age 79 +/- 6 years; all had CHA2DS2-VASc
      score >=2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed
      98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%)
      specificity. The incremental cost-effectiveness ratio of extending iECG screening
      into the community, based on 55% warfarin prescription adherence, would be
      $AUD5,988 (?3,142; $USD4,066) per Quality Adjusted Life Year gained and
      $AUD30,481 (?15,993; $USD20,695) for preventing one stroke. Sensitivity analysis
      indicated cost-effectiveness improved with increased treatment
      adherence.Screening with iECG in pharmacies with an automated algorithm is both
      feasible and cost-effective. The high and largely preventable
      stroke/thromboembolism risk of those with newly identified AF highlights the
      likely benefits of community AF screening. Guideline recommendation of community
      iECG AF screening should be considered. 

PMID- 24687082
TI  - BE, DO, and modal auxiliaries of 3-year-old African American English speakers.
AB  - PURPOSE: This study examined African American English-speaking children's use of
      BE, DO, and modal auxiliaries. METHOD: The data were based on language samples
      obtained from 48 three-year-olds. Analyses examined rates of marking by auxiliary
      type, auxiliary surface form, succeeding element, and syntactic construction and
      by a number of child variables. RESULTS: The children produced 3 different types
      of marking (mainstream overt, nonmainstream overt, zero) for auxiliaries, and the
      distribution of these markings varied by auxiliary type. The children's
      nonmainstream dialect densities were related to their marking of BE and DO but
      not modals. Marking of BE was influenced by its surface form and the succeeding
      verbal element, and marking of BE and DO was influenced by syntactic
      construction. CONCLUSIONS: Results extend previous studies by showing dialect
      specific effects for children's use of auxiliaries and by showing these effects
      to vary by auxiliary type and children's nonmainstream dialect densities. Some
      aspects of the children's auxiliary systems (i.e., pattern of marking across
      auxiliaries and effects of syntactic construction) were also consistent with what
      has been documented for children who speak other dialects of English. These
      findings show dialect-specific and dialect-universal aspects of African American
      English to be present early in children's acquisition of auxiliaries.

PMID- 24687083
TI  - Articulatory and acoustic correlates of contrastive focus in congenitally blind
      adults and sighted adults.
AB  - PURPOSE: The role of vision in speech representation was investigated in
      congenitally blind speakers and sighted speakers by studying the correlates of
      contrastive focus, a prosodic condition in which phonemic contrasts are enhanced.
      It has been reported that the lips (visible articulators) are less involved in
      implementing the rounding feature for blind speakers. If the weight of visible
      gestures in speech representation is reduced in blind speakers, they should show
      different strategies to mark focus-induced prominence. METHOD: Nine congenitally
      blind French speakers and 9 sighted French speakers were recorded while uttering
      sentences in neutral and contrastive focus conditions. Internal lip area, upper
      lip protrusion, and acoustic values (formants, fundamental frequency, duration,
      and intensity) were measured. RESULTS: In the acoustic domain, both groups
      signaled focus by using comparable values of fundamental frequency, intensity,
      and duration. Formant values in sighted speakers were more affected by the
      prosodic condition. In the articulatory domain, sighted speakers significantly
      altered lip geometry in the contrastive focus condition compared with the neutral
      condition, whereas blind speakers did not. CONCLUSION: These results suggest that
      implementation of prosodic focus is affected by congenital visual deprivation.
      The authors discuss how these findings can be interpreted in the framework of the
      perception-for-action-control theory.

PMID- 24687084
TI  - A new lamin a mutation associated with acrogeria syndrome.

PMID- 24687085
TI  - Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable
      long-term remissions with imatinib.
AB  - Myeloid neoplasms and eosinophilia with rearrangements of PDGFRB are uncommon
      Philadelphia-negative myeloproliferative neoplasms. Patients are typically male,
      with morphologic features of a Philadelphia-negative chronic myeloproliferative
      syndrome or chronic myelomonocytic leukemia with eosinophilia. Reciprocal
      translocations involving PDGFRB result in fusion genes with constitutively
      activated receptor tyrosine kinase sensitive to inhibition with imatinib. We
      present an updated and expanded analysis of a cohort of 26 such patients treated
      with imatinib. After a median follow-up of 10.2 years (range, 1.8-17 years), the
      10-year overall survival rate was 90% (95% confidence interval, 64%-97%); after
      median imatinib duration of 6.6 years (range, 0.1-12 years), the 6-year
      progression-free survival rate was 88% (95% confidence interval, 65%-96%). Of the
      patients, 96% responded; no patients who achieved a complete cytogenetic (n = 13)
      or molecular (n = 8) remission lost their response or progressed to blast crisis.
      Imatinib is well-tolerated and achieves excellent long-term responses in patients
      with PDGFRB rearrangements. 

PMID- 24687086
TI  - Heat shock protein vaccination and directed IL-2 therapy amplify tumor immunity
      rapidly following bone marrow transplantation in mice.
AB  - Tumor relapse is the primary cause of mortality in patients with hematologic
      cancers following autologous hematopoietic stem cell transplantation (HSCT).
      Vaccination early after HSCT can exploit both the state of lymphopenia and
      minimal residual disease for generating antitumor immunity. Here, multiple
      vaccinations using lymphoma cells engineered to secrete heat shock protein fusion
      gp96-Ig within 2 weeks of T cell-replete syngeneic HSCT led to cross-presentation
      and increased survival of lymphoma-bearing mice. To enhance vaccine efficacy,
      interleukin (IL)-2 was directed to predominantly memory phenotype CD8(+) T
      lymphocytes and natural killer (NK) cells via administration bound to anti-IL-2
      monoclonal antibody clone S4B6 (IL-2S4B6). Combination therapy with gp96-Ig
      vaccination and coordinated infusions of IL-2S4B6 resulted in marked prolongation
      of survival, which directly correlated with ~500% increase in effector CD8(+) T
      cell numbers. Notably, this dual regimen elicited large increases in both donor
      CD8(+) T and NK cells, but not CD4(+) T lymphocytes; the former 2 populations are
      essential for both vaccine efficacy and protection against opportunistic
      infections after HSCT. Indeed, IL-2S4B6-treated HSCT recipients infected with
      Listeria monocytogenes exhibited decreased bacterial levels. These preclinical
      studies validate a new strategy particularly well suited to the post-HSCT
      environment, which may augment adaptive and innate immune function in patients
      with malignant disease receiving autologous HSCT.

PMID- 24687087
TI  - Adherence to the Mediterranean diet is associated with lower platelet and
      leukocyte counts: results from the Moli-sani study.
AB  - Platelet (PLT) and white blood cell (WBC) counts are 2 markers of inflammation
      and have been linked to the risk for cerebrovascular and coronary heart disease.
      A Mediterranean diet (MD) has been associated with reduced inflammation and
      mortality for major chronic diseases. We aimed at evaluating the association
      between the MD and both PLT and WBC counts. This cross-sectional analysis in a
      population-based cohort study included 14,586 healthy Italian citizens enrolled
      within the Moli-sani study. Adherence to MD was appraised by either the MD Score
      (MDS) or the Italian Mediterranean Index (IMI). PLT and WBC counts were both
      inversely related to MD adherence (MDS: P < .0001 and P = .008, respectively). As
      compared with those with poorer MD adherence, subjects with greater adherence had
      both reduced odds of being in the highest PLT-count group (MDS: odds ratio =
      0.50; 95% confidence interval, 0.31-0.80) and increased odds of being in the
      lowest WBC-count group (IMI: odds ratio = 1.41; 95% confidence interval, 1.07
      1.86). The association between WBC count and MDS disappeared when further
      adjusted for PLT count, whereas the association between PLT count and the MD was
      not affected by adjustment for WBCs. Food antioxidant and dietary fiber content
      modified the inverse association between MDS and WBC count and partially
      accounted for the association with PLTs.

PMID- 24687089
TI  - The harms of an unnecessary preoperative echocardiogram: a teachable moment.

PMID- 24687088
TI  - Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs
      cytarabine/daunorubicin in older adults with untreated AML.
AB  - CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver
      synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed
      older acute myeloid leukemia (AML) patients were randomized 2:1 to first-line CPX
      351 or 7+3 treatment. The goal was to determine efficacy and identify patient
      subgroups that may benefit from CPX-351 treatment. Response rate (complete
      remission + incomplete remission) was the primary end point, with event-free
      survival (EFS) and overall survival (OS) as secondary end points. The 126
      patients entered were balanced for disease and patient-specific risk factors.
      Overall, CPX-351 produced higher response rates (66.7% vs 51.2%, P = .07),
      meeting predefined criteria for success (P < .1). Differences in EFS and OS were
      not statistically significant. A planned analysis of the secondary AML subgroup
      demonstrated an improved response rate (57.6% vs 31.6%, P = .06), and
      prolongation of EFS (hazard ratio [HR] = 0.59, P = .08) and OS (HR = 0.46, P =
      .01). Recovery from cytopenias was slower after CPX-351 (median days to absolute
      neutrophil count >=1000: 36 vs 32; platelets >100 000: 37 vs 28) with more grade
      3-4 infections but without increase in infection-related deaths (3.5% vs 7.3%) or
      60-day mortality (4.7% vs 14.6%), indicating acceptable safety. These results
      suggest a clinical benefit with CPX-351, particularly among patients with
      secondary AML, and provide the rationale for a phase 3 trial currently underway
      in newly diagnosed secondary AML patients. This study is registered at
      Clinicaltrials.gov as #NCT00788892. 

PMID- 24687091
TI  - Ventricular-fold dynamics in human phonation.
AB  - PURPOSE: In this study, the authors aimed (a) to provide a classification of the
      ventricular-fold dynamics during voicing, (b) to study the aerodynamic impact of
      these motions on vocal-fold vibrations, and (c) to assess whether ventricular
      fold oscillations could be sustained by aerodynamic coupling with the vocal
      folds. METHOD: A 72-sample database of vocal gestures accompanying different
      acoustical events comprised high-speed cinematographic, audio, and
      electroglottographic recordings of 5 subjects. Combining the physiological
      correlates with a theoretical model of phonation, the vocal-ventricular
      aerodynamic interactions were investigated. RESULTS: A ventricular-fold motion is
      found during (de)crescendos, shout, throat singing, yodel, growls, and glides
      with transitions between registers. Three main types of dynamics are identified:
      slow nonoscillatory motion and fast oscillatory motion with aperiodical or
      periodical vibrations. These patterns accompany a change in voice quality, pitch,
      and/or intensity. Alterations of glottal-oscillatory amplitude, frequency, and
      contact were predicted. It is shown that a ventricular oscillation can be
      initiated and sustained by aerodynamic coupling with the vocal folds.
      CONCLUSIONS: Vocal-ventricular aerodynamic interactions can alter, enhance, or
      suppress vocal-fold vibrations or leave them unchanged, depending on the
      ventricular-fold dynamics involved. Depending on its variation in time, a similar
      level of ventricular-fold adduction impacts the glottal vibratory magnitude and
      contact much differently.

PMID- 24687090
TI  - A rapid, site-selective and efficient route to the dual modification of DARPins.
AB  - Designed ankyrin repeat proteins (DARPins) are valuable tools in both
      biochemistry and medicine. Herein we describe a rapid, simple method for the dual
      modification of DARPins by introduction of cysteine mutations at specific
      positions that results in a vast difference in their thiol nucleophilicity,
      allowing for clean sequential modification. 

PMID- 24687092
TI  - Fabrication of MoS2 nanosheet@TiO2 nanotube hybrid nanostructures for lithium
      storage.
AB  - MoS2 nanosheet@TiO2 nanotube hybrid nanostructures were successfully prepared by
      a facile two-step method: prefabrication of porous TiO2 nanotubes based on a sol
      gel method template against polymeric nanotubes, and then assembly of MoS2
      nanoclusters that consist of ultrathin nanosheets through a solvothermal process.
      These hybrid nanostructures were characterized by scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX)
      spectroscopy, X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET) analysis.
      When evaluated as an electrode material for lithium ion batteries, the results of
      the electrochemical test show that the unique MoS2 nanosheet@TiO2 nanotube hybrid
      nanostructures exhibit outstanding lithium storage performances with high
      specific capacity and excellent rate capability. The smart architecture of the
      MoS2 nanosheet@TiO2 nanotube hybrid nanostructures makes a prominent contribution
      to the excellent electrochemical performance. 

PMID- 24687093
TI  - Tetra-sulfonate phthalocyanine zinc-bovine serum albumin conjugate-mediated
      photodynamic therapy of human glioma.
AB  - BACKGROUND: Glioma is the most common brain malignancy with poor prognosis. The
      current treatments for gliomas are mainly based on surgery, chemotherapy, and
      radiotherapy, which exhibit limited efficacy. Photodynamic therapy (PDT) using
      photosensitizers has been applied to glioma therapy. However, different
      photosensitizers usually lead to different therapeutic effects and adverse
      reactions. OBJECTIVE: This study investigates the anti-tumor effect of
      photosensitizer ZnPcS4-BSA in xenograft glioma tumors. METHODS: The xenograft
      glioma tumor model was established by inoculating nude mice with U251 cells.
      Tumor growth was evaluated by tumor volume, weight, and inhibition rate. Cell
      apoptosis was evaluated using TUNEL staining. Vascular endothelial growth factor
      (VEGF) expression and microvessel density were measured by immunohistochemistry.
      RESULTS: Significant decreases in tumor volume and weight as well as significant
      increases in tumor inhibition rate, cell apoptosis, VEGF expression, and
      microvessel density were observed in mice in the low- and high-dose PDT groups
      compared to the control, irradiation alone, and photosensitizer alone groups. No
      significant difference in cytotoxicity was observed between control group and
      photosensitizer alone group. Photosensitizer ZnPcS4-BSA significantly inhibited
      xenograft glioma tumor growth through induction of apoptosis. CONCLUSION: PDT
      using ZnPcS4-BSA may be effective for the therapy of gliomas.

PMID- 24687094
TI  - Poisson's ratio over two centuries: challenging hypotheses.
AB  - This article explores Poisson's ratio, starting with the controversy concerning
      its magnitude and uniqueness in the context of the molecular and continuum
      hypotheses competing in the development of elasticity theory in the nineteenth
      century, moving on to its place in the development of materials science and
      engineering in the twentieth century, and concluding with its recent re-emergence
      as a universal metric for the mechanical performance of materials on any length
      scale. During these episodes France lost its scientific pre-eminence as paradigms
      switched from mathematical to observational, and accurate experiments became the
      prerequisite for scientific advance. The emergence of the engineering of metals
      followed, and subsequently the invention of composites-both somewhat separated
      from the discovery of quantum mechanics and crystallography, and illustrating the
      bifurcation of technology and science. Nowadays disciplines are reconnecting in
      the face of new scientific demands. During the past two centuries, though, the
      shape versus volume concept embedded in Poisson's ratio has remained invariant,
      but its application has exploded from its origins in describing the elastic
      response of solids and liquids, into areas such as materials with negative
      Poisson's ratio, brittleness, glass formation, and a re-evaluation of traditional
      materials. Moreover, the two contentious hypotheses have been reconciled in their
      complementarity within the hierarchical structure of materials and through
      computational modelling.

PMID- 24687095
TI  - Supporting narrative retells for people with aphasia using augmentative and
      alternative communication: photographs or line drawings? Text or no text?
AB  - PURPOSE: The purpose of this study was to examine how the interface design of an
      augmentative and alternative communication (AAC) device influences the
      communication behaviors of people with aphasia during a narrative retell task.
      METHOD: A case-series design was used. Four narratives were created on an AAC
      device with combinations of personally relevant (PR) photographs, line drawings
      (LDs), and text for each participant. The narrative retells were analyzed to
      describe the expressive modality units (EMUs) used, trouble sources experienced,
      and whether trouble sources were repaired. The researchers also explored the
      participants' perceived helpfulness of the interface features. RESULTS: The
      participants primarily used spoken EMUs to retell their narratives. They relied
      on PR photographs more frequently than LDs; however, they reported both picture
      types to be equally helpful. Text was frequently used and reported as helpful by
      all 4 people with aphasia. Participants experienced similar rates of trouble
      sources across conditions; however, they displayed unique trends for successful
      repairs of trouble sources. CONCLUSION: For narrative retells, LDs may serve as
      an effective visual support when PR photographs are unavailable. Individual
      assessment is necessary to determine the optimum combination of supports in AAC
      systems for people with aphasia.

PMID- 24687096
TI  - Crash and rebound of indigenous populations in lowland South America.
AB  - Lowland South America has long been a battle-ground between European colonization
      and indigenous survival. Initial waves of European colonization brought disease
      epidemics, slavery, and violence that had catastrophic impacts on indigenous
      cultures. In this paper we focus on the demography of 238 surviving populations
      in Brazil. We use longitudinal censuses from all known indigenous Brazilian
      societies to quantify three demographic metrics: 1) effects of European contact
      on indigenous populations; 2) empirical estimates of minimum viable population
      sizes; and 3) estimates of post-contact population growth rates. We use this
      information to conduct population viability analysis (PVA). Our results show that
      all surviving populations suffered extensive mortality during, and shortly after,
      contact. However, most surviving populations exhibit positive growth rates within
      the first decade post-contact. Our findings paint a positive demographic outlook
      for these indigenous populations, though long-term survival remains subject to
      powerful externalities, including politics, economics, and the pervasive illegal
      exploitation of indigenous lands. 

PMID- 24687097
TI  - Classroom-based narrative and vocabulary instruction: results of an early-stage,
      nonrandomized comparison study.
AB  - PURPOSE: This nonrandomized feasibility study was designed to provide a
      preliminary assessment of the impact of a narrative and vocabulary instruction
      program provided by a speech-language pathologist (SLP) in a regular classroom
      setting. METHOD: Forty-three children attending 2 first-grade classrooms
      participated in the study. Children in each classroom were divided into high- and
      low-risk subgroups on the basis of their performance on a narrative test.
      Narrative and vocabulary instruction was provided by an SLP in 1 classroom for
      three 30-min periods per week for 6 weeks. RESULTS: The children in the
      experimental classroom made clinically significant improvements on narrative and
      vocabulary measures; children in the comparison classroom did not. Within the
      experimental classroom, children in the high-risk subgroup demonstrated greater
      gains in narration and fewer gains in vocabulary than children in the low-risk
      subgroup. There were no subgroup differences in the comparison classroom.
      CONCLUSION: These preliminary results provide early evidence of the feasibility
      of implementing a narrative instruction program in a classroom setting. Children
      at a high risk for language difficulties appeared to profit more from the
      narrative instruction than from the embedded vocabulary instruction. More
      extensive research on this instructional program is warranted.

PMID- 24687098
TI  - Vocabulary gain among children with language disorders: contributions of
      children's behavior regulation and emotionally supportive environments.
AB  - PURPOSE: Behavior regulation is a positive predictor of language outcomes for
      children with typically developing language skills, and children with language
      disorders are at greater risk for difficulties with behavior regulation. This
      study investigated the unique role of behavior regulation on vocabulary gain for
      children receiving language therapy in the public schools as well as the unique
      and moderating influence of emotional support within therapy sessions on
      outcomes. METHOD: A total of 121 kindergarten and 1st-grade students with
      language disorders, nested within 42 speech-language pathologists (SLPs),
      participated in the study. Direct child measures, indirect child measures, and
      therapy session videotapes were used for all analyses. RESULTS: Hierarchical
      linear modeling indicated a positive association between children's behavior
      regulation and vocabulary gain. The emotional support of therapy sessions was not
      a significant predictor of vocabulary gain. CONCLUSIONS: Results from this study
      suggest that children's behavior regulation is a significant predictor of
      vocabulary gain for children with language disorders; children with higher
      behavior regulation gain more over the academic year than do peers with lower
      behavior regulation. Findings highlight the importance of SLPs considering
      children's behavior regulation when planning and implementing therapy.

PMID- 24687100
TI  - It's time to meet our criminal justice partners halfway.

PMID- 24687102
TI  - Law & psychiatry: Assisting people in recovery who have criminal records to reach
      their employment goals.
AB  - Working, a goal of most people in recovery from mental disorders, can be impeded
      by legal exclusions and by employers' rejections based on an applicant's criminal
      record. This column describes established tools that can partially lower these
      barriers and recent legal developments that provide additional strategies, in
      particular the Equal Employment Opportunity Commission's Enforcement Guidance.
      These developments address the permissible use of arrest and conviction
      information in employment contexts, focusing on individualized consideration of
      specific factors, including rehabilitation. The authors also suggest strategies
      for job interview preparation that, when combined with job retention planning,
      can improve clients' prospects of achieving their employment goals. 

PMID- 24687099
TI  - Chlorella induces stomatal closure via NADPH oxidase-dependent ROS production and
      its effects on instantaneous water use efficiency in Vicia faba.
AB  - Reactive oxygen species (ROS) have been established to participate in stomatal
      closure induced by live microbes and microbe-associated molecular patterns
      (MAMPs). Chlorella as a beneficial microorganism can be expected to trigger
      stomatal closure via ROS production. Here, we reported that Chlorella induced
      stomatal closure in a dose-and time-dependent manner in epidermal peels of Vicia
      faba. Using pharmacological methods in this work, we found that the Chlorella
      induced stomatal closure was almost completely abolished by a hydrogen peroxide
      (H2O2) scavenger, catalase (CAT), significantly suppressed by an NADPH oxidase
      inhibitor, diphenylene iodonium chloride (DPI), and slightly affected by a
      peroxidase inhibitor, salicylhydroxamic acid (SHAM), suggesting that ROS
      production involved in Chlorella-induced stomatal closure is mainly mediated by
      DPI-sensitive NADPH oxidase. Additionally, Exogenous application of optimal
      concentrations of Chlorella suspension improved instantaneous water use
      efficiency (WUEi) in Vicia faba via a reduction in leaf transpiration rate (E)
      without a parallel reduction in net photosynthetic rate (Pn) assessed by gas
      exchange measurements. The chlorophyll fluorescence and content analysis further
      demonstrated that short-term use of Chlorella did not influence plant
      photosynthetic reactions center. These results preliminarily reveal that
      Chlorella can trigger stomatal closure via NADPH oxidase-dependent ROS production
      in epidermal strips and improve WUEi in leave levels. 

PMID- 24687103
TI  - Personal accounts: Trying to go green!

PMID- 24687104
TI  - Race, stigma, and mental health referrals among clients of aging services who
      screened positive for depression.
AB  - OBJECTIVES: This study examined rates of anticipated stigma and its impact on
      successful mental health referrals among elderly clients of home-delivered
      nutrition services who met criteria for depression. METHODS: Elderly clients
      (N=732) admitted to a home meal program between December 2004 and June 2006 were
      assessed for depression, cognitive impairment, and anticipated stigma. Gender and
      race comparisons were conducted, and predictors of receiving a mental health
      referral were identified. RESULTS: African Americans were more likely than
      Caucasians to report high anticipated stigma, and African-American men reported
      the highest mean scores for anticipated stigma. There were no significant
      differences between African Americans and Caucasians in rates of depression or
      mental health referrals. For clients with depression, low anticipated stigma,
      younger age, and an interaction of race and gender predicted receipt of a mental
      health referral. CONCLUSIONS: Anticipated stigma can hinder the process of
      referring older adults for mental health treatment.

PMID- 24687105
TI  - Physicians' influence on primary care patients' reluctance to use mental health
      treatment.
AB  - OBJECTIVES: The study examined attitudes of primary care patients toward mental
      health treatment and whether ambivalent or negative attitudes change after
      patients receive recommendations from their primary care physicians to seek
      treatment from a mental health professional. METHODS: Data were collected in face
      to-face interviews with 902 Jewish patients aged 25-75 in eight primary care
      clinics in Israel. Measures included validated mental health instruments and a
      vignette eliciting patients' readiness to consider treatment and potential
      influence of a physician's recommendation. RESULTS: Initially, almost half of
      patients were reluctant to consider specialized mental health treatment. The
      probability of having a more positive attitude after the physician's
      recommendation was significantly higher among patients with more severe clinical
      diagnoses. CONCLUSIONS: A major finding was the positive impact of primary care
      physicians' recommendations on reluctant patients. Encouraging physicians to
      discuss mental health issues would likely promote more positive attitudes and
      increase patients' willingness to access treatment.

PMID- 24687106
TI  - Safety and privacy outcomes from a moderated online social therapy for young
      people with first-episode psychosis.
AB  - OBJECTIVE: Internet-based treatments for early psychosis offer considerable
      promise, but safety and security need to be established. This study pilot tested
      Horyzons, a novel online treatment application that integrates purpose-built
      moderated social networking with psychoeducation for recovery from early
      psychosis. METHODS: Safety, privacy, and security were evaluated during a one
      month single-group trial with 20 young consumers recovering from early psychosis
      who were recruited in Melbourne, Australia. Known clinical risk factors informed
      the safety protocol. Safety, privacy, and security were evaluated with respect to
      relapse and self-harm, users' perceptions of safety and privacy, and activity
      using Horyzons. RESULTS: No clinical or security problems with use of Horyzons
      were noted. Participants described feeling safe and trusting Horyzons.
      CONCLUSIONS: Private moderated online social networking combined with
      psychoeducation was a safe and secure therapeutic environment for consumers
      recovering from a first episode of psychosis. Testing the intervention in a
      randomized controlled trial is warranted.

PMID- 24687107
TI  - Communicating a schizophrenia diagnosis to patients and families: a qualitative
      study of mental health clinicians.
AB  - OBJECTIVE: The aim of this research was to explore mental health clinicians'
      experiences and perceptions of discussing a diagnosis of schizophrenia with their
      patients. The results of this research will inform a communication skills
      training program for psychiatry trainees. METHODS: Semistructured interviews were
      conducted with 16 mental health clinicians from public mental health services in
      New South Wales, Australia. Interviews were recorded and transcribed for
      qualitative analysis. RESULTS: Although most clinicians supported the need to
      give patients a named diagnosis of schizophrenia, most gave multiple reasons for
      not doing so in practice. The reasons given centered on concerns for the patient;
      they included fear of making an incorrect diagnosis, fear of the patient's
      distress, and harm from stigma. CONCLUSIONS: Mental health clinicians need to
      reflect on their own feelings, examine personal identification with their
      patients, and recognize the subtle interplay of hope and pessimism in their
      communication of a schizophrenia diagnosis.

PMID- 24687108
TI  - Social cognition and interaction training: preliminary results of an RCT in a
      community setting in Israel.
AB  - OBJECTIVE: Social cognition and interaction training (SCIT) has shown promise in
      improving consumers' social cognition and functioning, in both inpatient and
      outpatient settings. This randomized controlled trial examined the effectiveness
      of SCIT among persons with serious mental illness living in community settings in
      Israel. METHODS: Fifty-five participants in social-mentoring services were
      assigned randomly to SCIT with social mentoring or to social mentoring only.
      Emotion recognition, theory of mind, attributional bias, and social functioning
      were assessed at baseline (February 2010) and about six months later, upon
      completion of the intervention. RESULTS: Interactions between time of measurement
      and group were significant for theory of mind and social engagement. Emotion
      recognition by the SCIT group improved significantly, but the time * group
      interaction for this variable was not significant. CONCLUSIONS: This study
      provides preliminary evidence that SCIT plus social mentoring improves social
      cognition and functioning among persons with severe mental illness who are living
      in the community.

PMID- 24687109
TI  - Extended mental health service utilization among survivors of the Oklahoma City
      bombing.
AB  - OBJECTIVE: The study assessed survivors of Oklahoma City's 1995 bombing seven
      years postdisaster to identify long-term mental health service use. METHODS:
      Psychiatric disorders and disaster-related variables were assessed for 99
      survivors at seven years postdisaster with the Diagnostic Interview Schedule for
      DSM-IV and its Disaster Supplement. RESULTS: Of the 99 survivors, 86% received
      services during the seven years. Use was associated with female sex, injury or
      hospitalization, and posttraumatic stress disorder (PTSD) or major depression.
      Informal interventions were usually initiated in the first six months. Treatment
      by psychiatrists, other professionals, and family doctors increased after the
      first month. Half the survivors with PTSD or depression received treatment from a
      psychiatrist. Only 15% of survivors took psychotropic medications. Although 33%
      received treatment for more than one year, only 7% were receiving services at
      seven years. CONCLUSIONS: Although service needs decreased over time, results
      support provision of diverse services adapted to changing needs.

PMID- 24687110
TI  - Refocusing gun policy.

PMID- 24687111
TI  - Refocusing gun policy: in reply.

PMID- 24687112
TI  - Suicide risk assessment and risk of suicide in schizophrenia.

PMID- 24687114
TI  - Internet use among veterans with severe mental illness.

PMID- 24687113
TI  - Suicide risk assessment and risk of suicide in schizophrenia: in reply.

PMID- 24687117
TI  - Supported metal catalysts for alcohol/sugar alcohol steam reforming.
AB  - Despite extensive studies on hydrogen production via steam reforming of alcohols
      and sugar alcohols, catalysts typically suffer a variety of issues from poor
      hydrogen selectivity to rapid deactivation. Here, we summarize recent advances in
      fundamental understanding of functionality and structure of catalysts for
      alcohol/sugar alcohol steam reforming, and provide perspectives on further
      development required to design highly efficient steam reforming catalysts. 

PMID- 24687118
TI  - The battle for the "green" polymer. Different approaches for biopolymer
      synthesis: bioadvantaged vs. bioreplacement.
AB  - Biopolymers have been used throughout history; however, in the last two centuries
      they have seen a decrease in their utilization as the proliferation of
      inexpensive and mass-produced materials from petrochemical feedstocks quickly
      became better-suited to meeting society's needs. In recent years, high petroleum
      prices and the concern of society to adopt greener and cleaner products has led
      to an increased interest in biorenewable polymers and the use of sustainable
      technologies to produce them. Industrial and academic researchers alike have
      targeted several routes for producing these renewable materials. In this
      perspective, we compare and contrast two distinct approaches to the economical
      realization of these materials. One mentality that has emerged we term
      "bioreplacement", in which the fields of synthetic biology and catalysis
      collaborate to coax petrochemical monomers from sugars and lignocellulosic
      feedstocks that can subsequently be used in precisely the same ways to produce
      precisely the same polymers as we know today. For example, the metabolic
      engineering of bacteria is currently being explored as a viable route to common
      monomers such as butadiene, isoprene, styrene, acrylic acid, and sebacic acid,
      amongst others. Another motif that has recently gained traction may be referred
      to as the "bioadvantage" strategy, where the multifunctional "monomers" given to
      us by nature are combined in novel ways using novel chemistries to yield new
      polymers with new properties; for these materials to compete with their petroleum
      based counterparts, they must add some advantage, for example less cost. For
      instance, acrylated epoxidized soybean oil readily undergoes polymerization to
      thermosets and recently, thermoplastic rubbers. Additionally, many plants produce
      pre-polymeric or polymeric materials that require little or no post modification
      to extract and make use of these compounds. 

PMID- 24687119
TI  - Low invasive in vivo tissue sampling for monitoring biomarkers and drugs during
      surgery.
AB  - The techniques currently used for drug, metabolite, and biomarker determination
      are based on sample collection, and therefore they are not suitable for repeated
      analysis because of the high invasiveness. Here, we present a novel method of
      biochemical analysis directly in organ during operation without need of a
      separate sample collection step: solid-phase microextraction (SPME). The approach
      is based on flexible microprobe coated with biocompatible extraction phase that
      is inserted to the tissue with no damage or disturbance of the organ. The method
      was evaluated during lung and liver transplantations using normothermic ex vivo
      liver perfusion (NEVLP) and ex vivo lung perfusion (EVLP). The study demonstrated
      feasibility of the method to extract wide range of endogenous compounds and
      drugs. Statistical analysis allowed observing metabolic changes of lung during
      cold ischemic time, perfusion, and reperfusion. It was also demonstrated that the
      level of drugs and their metabolites can be monitored over time. Based on the
      methylprednisolone as a selected example, the impairment of enzymatic properties
      of liver was detected in the injured organs but not in healthy control. This
      finding was supported by changes in pathways of endogenous metabolites. The SPME
      probe was also used for analysis of perfusion fluid using stopcock connection.
      The evaluation of biochemical profile of perfusates demonstrated potential of the
      approach for monitoring organ function during ex vivo perfusion. The simplicity
      of the device makes it convenient to use by medical personnel. With the
      microprobe, different areas of the organ or various organs can be sampled
      simultaneously. The technology allows assessment of organ function by biochemical
      profiling, determination of potential biomarkers, and drug monitoring. The use of
      this method for preintervention analysis could enhance the decision-making
      process for the best possible personalized approach, whereas post-transplantation
      monitoring would be used for graft assessments and fast response in case of organ
      failure. 

PMID- 24687122
TI  - Arterial stiffness as a potential determinant of beta-amyloid deposition.

PMID- 24687120
TI  - Vitronectin-binding PAI-1 protects against the development of cardiac fibrosis
      through interaction with fibroblasts.
AB  - Plasminogen activator inhibitor-1 (PAI-1) promotes or abates fibrotic processes
      occurring in different organs. Binding of PAI-1 to vitronectin, an extracellular
      matrix component, may inhibit vitronectin-integrin complex-mediated cellular
      responses in pathophysiological conditions. To investigate the importance of
      plasmin suppression vs vitronectin-binding pathways of PAI-1 in cardiac fibrosis,
      we studied uninephrectomized mice fed a high salt diet and infused with
      angiotensin II (Ang II) together with different PAI-1 variants, including PAI-1AK
      (AK) that inhibits plasminogen activators but does not bind vitronectin, PAI-1RR
      (RR) that binds vitronectin but does not have protease inhibitory effects or
      control PAI-1 (CPAI), the control mutant that has similar molecular backbone and
      half-life as AK and RR while retaining all functions of native PAI-1. Compared
      with RR and CPAI, non-vitronectin-binding AK significantly increased expression
      of cardiac fibroblast marker, periostin (Ang+AK 8.40+/-3.55 vs Ang+RR 2.23+/-0.44
      and Ang+CPAI 2.33+/-0.12% positive area, both P<0.05) and cardiac fibrosis
      (Ang+AK 1.79+/-0.26% vs Ang+RR 0.91+/-0.18% and Ang+CPAI 0.81+/-0.12% fibrotic
      area, both P<0.05), as well as Col1 mRNA (Ang+AK 12.81+/-1.84 vs Ang+RR 4.04+/
      1.06 and Ang+CPAI 5.23+/-1.21 fold increase, both P<0.05). To elucidate
      mechanisms underlying the protective effects of vitronectin-binding PAI-1 against
      fibrosis, fibroblasts from normal adult human ventricles were stimulated with Ang
      and different PAI-1 variants. Protease inhibitory AK and CPAI increased
      supernatant fibronectin, while decreasing plasminogen activator/plasmin
      activities and matrix metalloproteinase. RR and CPAI variants significantly
      reduced fibroblast expression of integrin beta3, vitronectin level in the
      supernatant and fibroblast adhesion to vitronectin compared with the non
      vitronectin-binding AK. Further, RR and CPAI preserved apoptotic, decreased anti
      apoptotic and proliferative activities in fibroblasts. Thus, PAI-1 promotes or
      protects against development of cardiac fibrosis differentially through the
      protease inhibitory pathway or through its binding to vitronectin. 

PMID- 24687121
TI  - Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in
      a mouse model of ureteral obstruction.
AB  - Dipeptidyl peptidase IV (DPPIV) is an exopeptidase that modulates the function of
      several substrates, among which insulin-releasing incretin hormones are the most
      well known. DPPIV also modulate substrates involved in inflammation, cell
      migration, and cell differentiation. Although DPPIV is highly expressed in
      proximal renal tubular cells, the role of DPPIV inhibition in renal disease is
      not fully understood. For this reason, we investigated the effects of LC15-0444,
      a DPPIV inhibitor, on renal function in a mouse model of renal fibrosis. Eight
      week-old C57/BL6 mice were subjected to unilateral ureteral obstruction (UUO) and
      were treated with LC15-0444 (a DPPIV inhibitor) at a dose of 150 mg/kg per day in
      food or vehicle for 14 days. DPPIV activity was significantly increased in
      obstructed kidneys, and reduced after treatment with LC15-0444. Administration of
      LC15-0444 resulted in a significant decrease in albuminuria, urinary excretion of
      8-isoprostane, and renal fibrosis. DPPIV inhibition also substantially decreased
      the synthesis of several proinflammatory and profibrotic molecules, as well as
      the infiltration of macrophages. UUO significantly increased, and LC15-0444
      markedly suppressed, levels of phosphorylated Smad2/3, TGFbeta1, toll-like
      receptor 4, high-mobility group box-1, NADPH oxidase 4, and NF-kappaB. These
      results suggest that activation of DPPIV in the kidney has a role in the
      progression of renal disease and that targeted therapy inhibiting DPPIV may prove
      to be a useful new approach in the management of progressive renal disease,
      independent of mechanisms mediated by glucagon-like peptide-1. 

PMID- 24687123
TI  - Adult hearing screening: health policy issues--what happens next?
AB  - PURPOSE: Ten percent of adults in England have some type of hearing loss and
      would greatly benefit from hearing aids or other forms of hearing management.
      However, 76% of these adults do not have hearing aids or other management. The
      impact of this unmet need can be substantial and has been linked to depression,
      social isolation, employment problems, loss of independence, and dementia. This
      article explores how hearing screening-universal, targeted, or opportunistic-can
      address prevalent, incident, and future needs for hearing services as well as
      better define the extent of need. METHOD: Adults age >=60 years living at home in
      England took part in a health survey, part of which was to determine the extent
      of need for hearing services in this population. Survey methods included a face
      to-face interview and hearing screening using pure tones as well as a self-report
      questionnaire on other health issues. RESULTS: The survey highlighted additional
      hearing-related factors that will enable referral decisions in primary care to be
      made with reasonable confidence that patients will use hearing aids and benefit
      from them. Some relevant nonhearing factors are also reported. CONCLUSION: There
      is a growing aging population with increasing needs and expectations for hearing
      services. Targeted screening and triage in primary care, as well as use of
      advanced technologies, are discussed for the future.

PMID- 24687124
TI  - Stuttering, temperament, and anxiety: data from a community cohort ages 2-4
      years.
AB  - PURPOSE: The purpose of this study was to ascertain whether and when temperament
      differences, including precursors of anxiety, emerge before onset and during
      stuttering development. METHOD: The authors prospectively studied temperament
      characteristics of a community cohort of children who stutter (N = 183) and
      children in the control group (N = 1,261). RESULTS: No significant differences
      were found at ages 2, 3, or 4 years between children who stutter and control
      children for approach or at ages 3 or 4 years for easy/difficult temperament.
      Both of these measures are precursors of anxiety. Significant differences were
      found for reactivity and persistence at age 3 years. Children who stutter were
      less reactive to environmental stimuli and had a reduced ability to attend to a
      task until completion. There was no evidence of this difference for persistence
      at age 4 years. Reactivity was not measured at age 4 years. CONCLUSION: On the
      basis of parents' responses to the Short Temperament Scale, preschoolers who
      stutter did not have innately different temperaments from control children on
      those temperament traits measured from ages 2 to 4 years. They showed no signs of
      temperament precursors of anxiety before stuttering onset or shortly after.
      Results suggest, at most, that temperament is influenced somehow during the
      period after stuttering onset but with a waning developmental influence
      subsequently.

PMID- 24687125
TI  - Effect of Verb Network Strengthening Treatment (VNeST) in persons with aphasia:
      extension and replication of previous findings.
AB  - PURPOSE: Verb Network Strengthening Treatment (VNeST) is an aphasia treatment
      that targets verbs (e.g., measure) and their related thematic roles (e.g.,
      carpenter-lumber). Previous studies reported encouraging results in a number of
      participants using single-subject design with improvements observed on naming,
      sentence production, and discourse. The purpose of the current study was to
      conduct a group analysis evaluating the effect of VNeST on similar outcomes.
      METHOD: A multiple baseline design across participants was conducted with 11
      persons with aphasia due to stroke. Wilcoxon signed-ranks tests were used to
      evaluate potential improvement from pre- to posttreatment and maintenance.
      Individual effect sizes were also calculated to evaluate magnitude of change
      within and across participants. RESULTS: Results showed significant improvement
      at posttreatment and maintenance on trained and untrained sentence probes and
      object and action naming. Improvement in the production of sentences not targeted
      in treatment was nonsignificant at posttreatment assessment but significant at
      maintenance. Moderate increases in percentage of complete utterances and overall
      informativeness were observed on discourse. CONCLUSION: The results of this study
      replicate previous findings and provide evidence that VNeST may promote specific
      and generalized lexical retrieval abilities and affect basic syntax production in
      both constrained and discourse production tasks.

PMID- 24687126
TI  - Direct N-acylation of azoles via a metal-free catalyzed oxidative cross-coupling
      strategy.
AB  - The KI-catalyzed N-acylation of azoles via direct oxidative coupling of C-H and N
      H bonds has been developed. It could be smoothly scaled up to gram synthesis of
      acyl azoles. The reaction occurred by the coupling of acyl radicals and azoles to
      form the acyl azole radical anion, followed by its further oxidation. 

PMID- 24687127
TI  - Cross-language perception of Japanese vowel length contrasts: comparison of
      listeners from different first language backgrounds.
AB  - PURPOSE: The purpose of this research was to compare the perception of Japanese
      vowel length contrasts by 4 groups of listeners who differed in their familiarity
      with length contrasts in their first language (L1; i.e., American English,
      Italian, Japanese, and Thai). Of the 3 nonnative groups, native Thai listeners
      were expected to outperform American English and Italian listeners, because vowel
      length is contrastive in their L1. Native Italian listeners were expected to
      demonstrate a higher level of accuracy for length contrasts than American English
      listeners, because the former are familiar with consonant (but not vowel) length
      contrasts (i.e., singleton vs. geminate) in their L1. METHOD: A 2-alternative
      forced-choice AXB discrimination test that included 125 trials was administered
      to all the participants, and the listeners' discrimination accuracy (d') was
      reported. RESULTS: As expected, Japanese listeners were more accurate than all 3
      nonnative groups in their discrimination of Japanese vowel length contrasts. The
      3 nonnative groups did not differ from one another in their discrimination
      accuracy despite varying experience with length contrasts in their L1. Only Thai
      listeners were more accurate in their length discrimination when the target vowel
      was long than when it was short. CONCLUSION: Being familiar with vowel length
      contrasts in L1 may affect the listeners' cross-language perception, but it does
      not guarantee that their L1 experience automatically results in efficient
      processing of length contrasts in unfamiliar languages. The extent of success may
      be related to how length contrasts are phonetically implemented in listeners' L1.

PMID- 24687128
TI  - Prevalence, correlates and trends in seroadaptive behaviours among men who have
      sex with men from serial cross-sectional surveillance in San Francisco, 2004
      2011.
AB  - OBJECTIVES: We sought to assess the prevalence and correlates of seroadaptive
      behaviours (i.e., sexual history incorporating some unprotected anal intercourse
      (UAI)) and conventional risk reduction behaviours (i.e., consistent condom use or
      no anal intercourse) among men who have sex with men (MSM) in San Francisco in
      2011. We compared the prevalence of seroadaptive behaviours between serial cross
      sectional surveys from 2004, 2008 and 2011. METHODS: We analysed data from the
      2011 wave of the National HIV Behavioral Surveillance system in San Francisco. We
      categorised men's self-reported sexual behaviour history in the past 6 months
      into a schema of seroadaptive behaviours and conventional risk reduction
      behaviours. We compared the prevalence of behaviour categories by self-reported
      HIV serostatus, HIV testing history, awareness of pre-exposure HIV prophylaxis
      (PrEP) and diagnosis of a sexually transmitted infection (STI). RESULTS:
      Seroadaptive behaviours remained common in San Francisco MSM, with a 2011
      prevalence of 46.6%, up from 35.9% in 2004. Consistent condom use or no anal
      intercourse was more common than seroadaptive behaviours in HIV-negative MSM, men
      who had not heard of PrEP and men without an STI diagnosis. Seroadaptive
      behaviours increased from 2004 to 2011. CONCLUSIONS: HIV seroadaptive behaviours
      remain common in San Francisco MSM, have increased in the last decade and are
      practiced differently by MSM with different sexual health knowledge and outcomes.
      Public health researchers and officials should continue to document the
      prevalence, intentionality, efficacy and safety of seroadaptive behaviours among
      diverse communities of MSM.

PMID- 24687129
TI  - Association between Mycoplasma genitalium infection and HIV acquisition among
      female sex workers in Uganda: evidence from a nested case-control study.
AB  - OBJECTIVES: Cross-sectional studies have shown a strong association between
      Mycoplasma genitalium and HIV infections. We previously reported that in a cohort
      of female sex workers in Uganda, M genitalium infection at baseline was
      associated with HIV seroconversion. Here we examine the temporal association
      between the M genitalium infection status shortly before HIV seroconversion and
      HIV acquisition. METHODS: A nested case-control study was conducted within a
      cohort of women at high risk for HIV in Kampala. Cases were those of women
      acquiring HIV within 2 years of enrolment. For each of the 42 cases, 3 controls
      were selected from women HIV negative at the visit when the corresponding case
      first tested HIV seropositive. The association between HIV acquisition and M
      genitalium infection immediately prior to HIV testing was analysed using
      conditional logistic regression. RESULTS: There was weak evidence of an
      association between M genitalium infection and HIV acquisition overall (crude
      OR=1.57; 95% CI 0.67 to 3.72, aOR=2.28: 95% CI 0.81 to 6.47). However, time of M
      genitalium testing affected the association (p value for effect
      modification=0.004). For 29 case-control sets with endocervical samples tested 3
      months prior to the first HIV-positive result, M genitalium infection increased
      the risk of HIV acquisition (crude OR=3.09; 95% CI 1.06 to 9.05, aOR=7.19; 95% CI
      1.68 to 30.77), whereas there was little evidence of an association among the 13
      case-control sets with samples tested at an earlier visit (crude OR=0.30: 95% CI
      0.04 to 2.51; aOR=0.34; 95% CI 0.02 to 5.94). CONCLUSIONS: Our study showed
      evidence of a temporal relationship between M genitalium infection and HIV
      acquisition that suggests that M genitalium infection may be a co-factor in the
      acquisition of HIV infection.

PMID- 24687131
TI  - One-pot synthesis of nitrogen and sulfur co-doped graphene as efficient metal
      free electrocatalysts for the oxygen reduction reaction.
AB  - Novel N, S co-doped graphene (NSG) was prepared by annealing graphene oxide with
      thiourea as the single N and S precursor. The NSG electrodes, as efficient metal
      free electrocatalysts, show a direct four-electron reaction pathway, high onset
      potential, high current density and high stability for the oxygen reduction
      reaction. 

PMID- 24687130
TI  - Clinical predictors of rectal lymphogranuloma venereum infection: results from a
      multicentre case-control study in the U.K.
AB  - OBJECTIVE: Since 2003, over 2000 cases of lymphogranuloma venereum (LGV) have
      been diagnosed in the U.K. in men who have sex with men (MSM). Most cases present
      with proctitis, but there are limited data on how to differentiate clinically
      between LGV and other pathology. We analysed the clinical presentations of rectal
      LGV in MSM to identify clinical characteristics predictive of LGV proctitis and
      produced a clinical prediction model. DESIGN: A prospective multicentre case
      control study was conducted at six U.K. hospitals from 2008 to 2010. Cases of
      rectal LGV were compared with controls with rectal symptoms but without LGV.
      METHODS: Data from 98 LGV cases and 81 controls were collected from patients and
      clinicians using computer-assisted self-interviews and clinical report forms.
      Univariate and multivariate logistic regression was used to compare symptoms and
      signs. Clinical prediction models for LGV were compared using receiver operating
      curves. RESULTS: Tenesmus, constipation, anal discharge and weight loss were
      significantly more common in cases than controls. In multivariate analysis,
      tenesmus and constipation alone were suggestive of LGV (OR 2.98, 95% CI 0.99 to
      8.98 and 2.87, 95% CI 1.01 to 8.15, respectively) and that tenesmus alone or in
      combination with constipation was a significant predictor of LGV (OR 6.97, 95% CI
      2.71 to 17.92). The best clinical prediction was having one or more of tenesmus,
      constipation and exudate on proctoscopy, with a sensitivity of 77% and
      specificity of 65%. CONCLUSIONS: This study indicates that tenesmus alone or in
      combination with constipation makes a diagnosis of LGV in MSM presenting with
      rectal symptoms more likely.

PMID- 24687134
TI  - Short-term disruption of diurnal rhythms after murine myocardial infarction
      adversely affects long-term myocardial structure and function.
AB  - RATIONALE: Patients in intensive care units are disconnected from their natural
      environment. Synchrony between environmental diurnal rhythms and intracellular
      circadian rhythms is essential for normal organ biology; disruption causes
      pathology. Whether disturbing rhythms after myocardial infarction (MI)
      exacerbates long-term myocardial dysfunction is not known. OBJECTIVE: Short-term
      diurnal rhythm disruption immediately after MI impairs remodeling and adversely
      affects long-term cardiac structure and function in a murine model. METHODS AND
      RESULTS: Mice were infarcted by left anterior descending coronary artery ligation
      (MI model) within a 3-hour time window, randomized to either a normal diurnal or
      disrupted environment for 5 days, and then maintained under normal diurnal
      conditions. Initial infarct size was identical. Short-term diurnal disruption
      adversely affected body metabolism and altered early innate immune responses. In
      the first 5 days, crucial for scar formation, there were significant differences
      in cardiac myeloperoxidase, cytokines, neutrophil, and macrophage infiltration.
      Homozygous clock mutant mice exhibited altered infiltration after MI, consistent
      with circadian mechanisms underlying innate immune responses crucial for scar
      formation. In the proliferative phase, 1 week after MI, this led to significantly
      less blood vessel formation in the infarct region of disrupted mice; by day 14,
      echocardiography showed increased left ventricular dilation and infarct
      expansion. These differences continued to evolve with worse cardiac structure and
      function by 8 weeks after MI. CONCLUSIONS: Diurnal rhythm disruption immediately
      after MI impaired healing and exacerbated maladaptive cardiac remodeling. These
      preclinical findings suggest that disrupted diurnal rhythms such as found in
      modern intensive care unit environments may adversely affect long-term patient
      outcome.

PMID- 24687135
TI  - Toy talk: simple strategies to create richer grammatical input.
AB  - PURPOSE: The purpose of this initial feasibility study was to determine whether
      brief instruction in toy talk would change grammatical properties of adult
      language, specifically 3rd person lexical noun phrase (NP) subjects. METHOD:
      Eighteen college students participated in the study. The use of 3rd person
      subjects was examined before and after instruction on toy talk strategies (i.e.,
      talk about the toys, give the item its name). Change in the input informativeness
      for tense (i.e., the proportion of verb forms marked for tense out of all verb
      forms) was also examined, although adults were not instructed on use of
      tense/agreement morphemes. RESULTS: Following instruction, statistically
      significant increases with large effect sizes were observed for use of 3rd person
      subjects, lexical NP subjects, and input informativeness for tense (Cohen's d =
      1.20, 2.08, and 0.89, respectively). CONCLUSIONS: These findings demonstrate that
      young adults can learn these simple strategies with relatively brief instruction,
      and the use of toy talk also changes the richness of tense/agreement marking in
      adult language input. Considerations for incorporating toy talk into existing
      language modeling practices and future plans for evaluating the efficacy of toy
      talk are discussed.

PMID- 24687132
TI  - Disruption of mammalian target of rapamycin complex 1 in macrophages decreases
      chemokine gene expression and atherosclerosis.
AB  - RATIONALE: The mammalian target of rapamycin complex 1 inhibitor, rapamycin, has
      been shown to decrease atherosclerosis, even while increasing plasma low-density
      lipoprotein levels. This suggests an antiatherogenic effect possibly mediated by
      the modulation of inflammatory responses in atherosclerotic plaques. OBJECTIVE:
      Our aim was to assess the role of macrophage mammalian target of rapamycin
      complex 1 in atherogenesis. METHODS AND RESULTS: We transplanted bone marrow from
      mice in which a key mammalian target of rapamycin complex 1 adaptor, regulatory
      associated protein of mTOR, was deleted in macrophages by Cre/loxP recombination
      (Mac-Rap(KO) mice) into Ldlr(-/-) mice and then fed them the Western-type diet.
      Atherosclerotic lesions from Mac-Rap(KO) mice showed decreased infiltration of
      macrophages, lesion size, and chemokine gene expression compared with control
      mice. Treatment of macrophages with minimally modified low-density lipoprotein
      resulted in increased levels of chemokine mRNAs and signal transducer and
      activator of transcription (STAT) 3 phosphorylation; these effects were reduced
      in Mac-Rap(KO) macrophages. Although wild-type and Mac-Rap(KO) macrophages showed
      similar STAT3 phosphorylation on Tyr705, Mac-Rap(KO) macrophages showed decreased
      STAT3Ser727 phosphorylation in response to minimally modified low-density
      lipoprotein treatment and decreased Ccl2 promoter binding of STAT3. CONCLUSIONS:
      The results demonstrate cross-talk between nutritionally induced mammalian target
      of rapamycin complex 1 signaling and minimally modified low-density lipoprotein
      mediated inflammatory signaling via combinatorial phosphorylation of STAT3 in
      macrophages, leading to increased STAT3 activity on the chemokine (C-C motif)
      ligand 2 (monocyte chemoattractant protein 1) promoter with proatherogenic
      consequences.

PMID- 24687133
TI  - Low serum ferroxidase I activity is associated with mortality in heart failure
      and related to both peroxynitrite-induced cysteine oxidation and tyrosine
      nitration of ceruloplasmin.
AB  - RATIONALE: Ceruloplasmin antioxidant function is mainly related to its
      ferroxidase I (FeOxI) activity, which influences iron-dependent oxidative and
      nitrosative radical species generation. Peroxynitrite, whose production is
      increased in heart failure (HF), can affect ceruloplasmin antioxidant function
      through amino acid modification. OBJECTIVE: We investigated the relationship
      between FeOxI and ceruloplasmin tyrosine and cysteine modification and explored
      in a cohort of patients with HF the potential clinical relevance of serum FeOxI.
      METHODS AND RESULTS: In patients with chronic HF (n=96, 76 +/- 9 years; New York
      Heart Association class, 2.9 +/- 0.8) and age-matched controls (n=35), serum
      FeOxI, FeOxII, ceruloplasmin, nitrotyrosine-bound ceruloplasmin, B-type
      natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were
      measured, and the patients were followed up for 24 months. Ceruloplasmin, B-type
      natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were
      increased in HF versus controls. FeOxI was decreased in HF (-20%) and inversely
      related to nitrotyrosine-bound ceruloplasmin (r, -0.305; P=0.003). In HF, FeOxI
      lower tertile had a mortality rate doubled compared with middle-higher tertiles.
      FeOxI emerged as a mortality predictor (hazard ratio, 2.95; 95% confidence
      intervals [1.29-6.75]; P=0.011) after adjustment for age, sex, hypertension,
      smoking, sodium level, estimated glomerular filtration rate, and high-sensitivity
      C-reactive protein. In experimental settings, peroxynitrite incubation of serum
      samples and isolated purified ceruloplasmin reduced FeOxI activity while
      increasing ceruloplasmin tyrosine nitration and cysteine thiol oxidation. Reduced
      glutathione prevented peroxynitrite-induced FeOxI drop, tyrosine nitration, and
      cysteine oxidation; flavonoid(-)-epicatechin, which prevented ceruloplasmin
      tyrosine nitration but not cysteine oxidation, partially impeded peroxynitrite
      induced FeOxI drop. CONCLUSIONS: Reduced activity of serum FeOxI is associated
      with ceruloplasmin nitration and reduced survival in patients with HF. Both
      ceruloplasmin tyrosine nitration and cysteine thiol oxidation may be operant in
      vivo in peroxynitrite-induced FeOxI activity inhibition.

PMID- 24687136
TI  - Speaking fundamental frequency and individual variability in Caucasian and
      African American school-age children.
AB  - PURPOSE: The purpose of this study was to examine the speaking fundamental
      frequency (SFF) and pitch sigma (individual SFF variability) of African American
      and Caucasian children ages 6 through 8 years. METHOD: Participants in this study
      included 63 Caucasian and African American children recruited from 6 urban
      schools and 1 day care center. All participants passed hearing and speech
      language screenings. Spontaneous speech samples for SFF measurement were elicited
      from each child in a quiet room in the school he or she attended. RESULTS:
      Results of this study found that there were no significant differences in SFF or
      pitch sigma as a function of the races or ages studied. It appeared that a single
      value for each variable could reasonably characterize African American and
      Caucasian children at ages 6, 7, or 8: 244.8 Hz for SFF (SD = 30.0 Hz) and 2.06
      semitones (STs) for pitch sigma (SD = 0.82 ST). CONCLUSIONS: This study is the
      most comprehensive to date on SFF and pitch sigma for African American and
      Caucasian children ages 6 to 8 years. Results supported previous observations
      that SFF is stable throughout the prepubescent years. Furthermore, findings also
      suggest that pitch sigma is stable across the ages of 6 to 8 years, regardless of
      race.

PMID- 24687137
TI  - Trainee GP who posted photos of patients online is told his fitness to practise
      is impaired.

PMID- 24687138
TI  - Dynamic weight loading in older people with hip fracture.
AB  - OBJECTIVE: Hip fractures have a high morbidity and mortality in elderly patients.
      Improving mobility outcomes is crucial in order to decrease the burden of this
      injury. The objective of this study was to investigate dynamic weight loading in
      older people with hip fractures using a new device. DESIGN: In an observational
      study, low-energy hip fracture patients were monitored one day per week with the
      FeetB@ck system during their admission. Pain, gait and balance scores were noted.
      Outcome measures of the FeetB@ck system are steps, walking bouts and loading
      rate. RESULTS: A total of 21 patients with hip fracture were included in the
      study (mean age 80.3 years (standard deviation 8.3 years)). The number of steps,
      walking bouts and loading rate had a positive linear relationship with
      rehabilitation (i.e. gait and balance scores) (p < 0.05). These parameters also
      differed significantly between patients with short (less than 8 weeks, n = 7),
      intermediate (between 8 and 12 weeks, n = 8) and long (longer than 12 weeks, n =
      6) of rehabilitation (p < 0.01). CONCLUSION: The loading rate is a sensitive
      weight loading parameter for analysis of dynamic weight loading during
      rehabilitation in elderly hip fracture patients. This parameter correlates with
      clinical improvement and can differentiate between fast and slow rehabilitation.

PMID- 24687139
TI  - Examining recombinant human TSH primed 131I therapy protocol in patients with
      metastatic differentiated thyroid carcinoma: comparison with the traditional
      thyroid hormone withdrawal protocol.
AB  - PURPOSE: Recombinant human thyroid-stimulating hormone (rhTSH)-based protocol is
      a promising recent development in the management of differentiated thyroid
      carcinoma (DTC). The objectives of this prospective study were: (1) to assess the
      feasibility and efficacy of the rhTSH primed (131)I therapy protocol in patients
      with DTC with distant metastatic disease, (2) to perform lesional dosimetry in
      this group of patients compared to the traditional protocol, (3) to document the
      practical advantages (patient symptoms and hospital stay) of the rhTSH protocol
      compared to the traditional thyroid hormone withdrawal protocol, (4) to document
      and record any adverse effect of this strategy, (5) to compare the renal function
      parameters, and (6) to compare the serum TSH values achieved in either of the
      protocols in this group of patients. METHODS: The study included 37 patients with
      metastatic DTC having lung or skeletal metastases or both. A comparison of
      lesional radiation absorbed dose, hospital stay, renal function tests, and
      symptom profile was undertaken between the traditional thyroid hormone withdrawal
      protocol and rhTSH-based therapy protocol. Dosimetric calculations of metastatic
      lesions were performed using lesion uptake and survey meter readings for
      calculation of effective half-life. Non-contrast-enhanced CT was used for
      assessment of tumor volume. Quality of life was assessed using the European
      Organization for Research and Treatment of Cancer (EORTC) QOL forms. A comparison
      of pretreatment withdrawal thyroglobulin (TG) was done with the withdrawal TG
      level 3 months after treatment. RESULTS: The mean effective half-life of (131)I
      in metastatic lesions was less during the rhTSH protocol (29.49 h) compared to
      the thyroid hormone withdrawal protocol (35.48 h), but the difference was not
      statistically significant (p = 0.056). The mean 24-h % uptake of the lesions
      during the traditional protocol (4.84 %) was slightly higher than the 24-h %
      uptake during the rhTSH protocol (3.56 %), but the difference was not found to be
      statistically significant (p = 0.301). The mean tumor radiation absorbed dose per
      mCi was less during the rhTSH protocol (6.04 rad/mCi) than during the thyroid
      hormone withdrawal protocol (8.68 rad/mCi), and the difference was statistically
      significant (p = 0.049), though visual analysis of the rhTSH posttherapy scans
      showed avid concentration of (131)I in the metastatic sites and revealed more
      lesions in 30 % of the patients compared to the traditional large dose scan and
      equal number of lesions in 65 % of the patients. Visual analysis of the
      traditional large dose scan, rhTSH pretreatment scan, and rhTSH posttherapy scans
      showed that the traditional large dose scan is better compared to the rhTSH 1 mCi
      scan as it showed more lesions in 19 of 37 patients (51.35 %). rhTSH posttherapy
      scans were better compared to the traditional large dose scans and rhTSH
      pretreatment scans. More lesions were seen on rhTSH posttherapy scans in 11 of 37
      patients (29.7 %) compared to the traditional large dose scans and in 24 of 37
      (64.86 %) patients compared to the rhTSH 1 mCi scans. Our findings demonstrate
      that the rhTSH primed pretreatment scan undertaken at 24 h after diagnostic dose
      is suboptimal to evaluate whether a metastatic lesion concentrates (131)I. The
      majority of these lesions demonstrated radioiodine accumulation in the
      posttreatment scan. Quality of life as assessed using EORTC QOL-3 forms clearly
      showed that rhTSH improved the quality of life of patients compared to the
      thyroid hormone withdrawal protocol. Functional scale and global health status
      were significantly better in the rhTSH protocol compared to the thyroid hormone
      withdrawal protocol (p < 0.001). The mean symptom scale score was significantly
      higher in the thyroid hormone withdrawal protocol (45.25) compared to the rhTSH
      protocol (13.59) (p < 0.001). Of the 20 patients, 4 (20 %) had more than 25 %
      increase in the TG value on follow-up. The median hospital stay of patients
      receiving (131)I therapy with the rhTSH protocol was shorter (2 days, range 2-8
      days) compared to the thyroid hormone withdrawal protocol (3 days, range 1-8
      days) and the difference was found to be statistically significant (p = 0.007).
      The mean serum creatinine level was significantly lower in the rhTSH protocol
      (0.826 mg/dl) than the thyroid hormone withdrawal protocol (0.95 mg/dl) (p =
      0.013), though the mean blood urea level of patients during the rhTSH therapy
      protocol was slightly higher (22.81 mg/dl) than during the thyroid hormone
      withdrawal protocol (21.91 mg/dl) without statistical significance (p = 0.55).
      The mean serum TSH on day 2 of the rhTSH protocol was 140.99 MUIU/ml (range 71
      176 MUIU/ml) compared to 72.62 MUIU/ml (range 2.05-154 MUIU/ml) in the
      traditional protocol after around 4-6 weeks of thyroid hormone withdrawal (p <
      0.05). CONCLUSION: Overall, the rhTSH primed (131)I therapy protocol was found to
      be feasible and a good alternative to the thyroid hormone withdrawal protocol in
      patients with metastatic DTC. The lesional dosimetry findings need to be further
      examined in subsequent studies. The rhTSH primed pretreatment scan at 24 h after
      diagnostic dose is suboptimal to determine whether a metastatic lesion
      concentrates (131)I and the posttreatment scan is important for the correct
      impression.

PMID- 24687140
TI  - A new approach towards the synthesis of pseudaminic acid analogues.
AB  - The pseudaminic acids are a family of 5,7-diamino-3,5,7,9-tetradeoxynonulosonic
      acids that are essential components of bacterial polysaccharides and
      glycoproteins. This paper describes our approach towards the synthesis of
      analogues of pseudaminic acid, and involves the efficient introduction of the
      requisite nitrogen functionalities from a readily available precursor. 

PMID- 24687142
TI  - Thinner subfoveal choroidal thickness in eyes with ocular ischemic syndrome than
      in unaffected contralateral eyes.

PMID- 24687141
TI  - An in vivo study of composite microgels based on hyaluronic acid and gelatin for
      the reconstruction of surgically injured rat vocal folds.
AB  - PURPOSE The objective of this study was to investigate local injection with a
      hierarchically microstructured hyaluronic acid-gelatin (HA-Ge) hydrogel for the
      treatment of acute vocal fold injury using a rat model. METHOD Vocal fold
      stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25
      MUl saline (placebo controls), HA-bulk, or HA-Ge hydrogel was injected into the
      lamina propria (LP) 5 days after surgery. The vocal folds were harvested at 3,
      14, and 28 days after injection and analyzed using hematoxylin and eosin staining
      and immunohistochemistry staining for macrophages, myofibroblasts, elastin,
      collagen type I, and collagen type III. RESULTS The macrophage count was
      statistically significantly lower in the HA-Ge group than in the saline group (p
      < .05) at Day 28. Results suggested that the HA-Ge injection did not induce
      inflammatory or rejection response. Myofibroblast counts and elastin were
      statistically insignificant across treatment groups at all time points. Increased
      elastin deposition was qualitatively observed in both HA groups from Day 3 to Day
      28, and not in the saline group. Significantly more elastin was observed in the
      HA-bulk group than in the uninjured group at Day 28. Significantly more collagen
      type I was observed in the HA-bulk and HA-Ge groups than in the saline group (p <
      .05) at Day 28. The collagen type I concentration in the HA-Ge and saline groups
      was found to be comparable to that in the uninjured controls at Day 28. The
      concentration of collagen type III in all treatment groups was similar to that in
      uninjured controls at Day 28. CONCLUSION Local HA-Ge and HA-bulk injections for
      acute injured vocal folds were biocompatible and did not induce adverse response.

PMID- 24687143
TI  - Improvement of mild retinopathy in type 2 diabetic patients correlates with
      narrowing of retinal arterioles. A prospective observational study.
AB  - PURPOSE: Diabetic retinopathy is one of the leading causes of blindness in the
      Western world. The disease is characterized by morphological lesions secondary to
      disturbances in retinal blood flow assumed to be related to disturbances in
      retinal autoregulation. However, there is a need for elucidating the relation
      between disturbances in diameter regulation of retinal vessels and the
      development of diabetic retinopathy in longitudinal studies. METHODS: Sixty-four
      patients with type 2 diabetes mellitus were subjected to measurement of pressure
      autoregulation of retinal arterioles using the Dynamic Vessel Analyzer (DVA) and
      measurement of retinal thickness using OCT scanning, and after a mean of 6.8
      years, 42 of the patients were re-examined. The vascular response was compared in
      patients in whom retinopathy had disappeared, was unchanged, or had worsened.
      RESULTS: At baseline, hemoglobin A1c (HbA1c) was significantly higher in the
      patients who would later experience worsening of diabetic retinopathy than in the
      other groups, but had been reduced at the follow-up examination. During the
      follow-up period, the resting diameter of retinal arterioles decreased
      significantly in the patients who experienced improvement in diabetic retinopathy
      but was unchanged in the other groups, whereas both the diameter response of
      retinal arterioles to isometric exercise and retinal thickness increased non
      significantly with worsening of retinopathy. CONCLUSIONS: The development of
      diabetic retinopathy is related to the diameter of retinal arterioles. Future
      clinical intervention studies should aim at investigating the effects of
      normalizing arteriolar diameters in diabetic retinopathy.

PMID- 24687144
TI  - Slit-lamp exophthalmometry, a novel technique.
AB  - PURPOSE: Exophthalmometry is clinically important for diagnoses, follow-up, and
      treatment decision-making. Through the years, several drawbacks and sources of
      error have been described when using Hertel and other exophthalmometers. METHODS:
      We describe a simple method of non-touch slit-lamp exophthalmometry. Comparing
      the results between Hertel and slit-lamp exophthalmometry on 60 patients with
      proptosis showed no statistically significant differences in the two methods.
      RESULTS: A total of 60 consecutive patients with proptosis were included. Thirty
      six cases (60 %) were women. Their mean age was 55.6 +/- 16.4 (median 57.5, range
      20-87) years. Only 5 % of the measurements had more than 2 mm difference between
      the two techniques. There were no significant differences in the measurements
      between the two methods. Intra-correlation coefficient is 0.96 for right side and
      0.956 for lest side. The Bland-Altman plot revealed good agreement. CONCLUSIONS:
      Slit-lamp exophthalmometry offers a simple, easily available, and reliable non
      touch technique that does not require an exophthalmometer.

PMID- 24687145
TI  - Pneumatic trabecular bypass versus trabeculotomy in the management of primary
      congenital glaucoma.
AB  - BACKGROUND: The optimal surgical management in primary congenital glaucoma (PCG)
      remains a subject of debate. The aim of this study was to assess efficacy of
      pneumatic trabecular bypass (PTB) in comparison to conventional trabeculotomy (T)
      in the treatment of PCG. METHODS: In a prospective comparative experimental
      study, one eye per child suffering from PCG underwent either PTB or T. Complete
      examinations were performed before surgery, postoperatively at one and seven
      days, then monthly for a minimum of six months. The main outcome measures were
      the IOP, number of IOP-lowering medications, change in cup/disc ratio, and
      corneal clarity. RESULTS: Seventeen eyes (patients) were operated on for PTB
      compared to 25 eyes (patients) in the T group. The mean (+/-SD, range)
      preoperative IOP in the PTB and T groups was 34.7 (6.4, 26-48) mmHg and 26.4
      (6.6, 18-44) mmHg, respectively, and these dropped at six months of follow-up to
      14.9 (3.6, 11-24) mmHg and 18.8 (8.0, 6-34) mmHg, respectively. The mean
      reductions of IOP were 55.87 %(+/-11) and 28.4 %(+/-28.8), (p = 0.001), where
      those for cup/disc ratio were 39.0 %(+/-29) and 17.5 %(+/-39.7) (p = 0.088) in
      the PTB and T groups, respectively. The number of IOP-lowering medications had
      dropped from 1.7 +/- 0.5 to 0.7 +/- 1.0 in PTB patients, compared to an
      insignificant change in the T group (0.64 +/- 0.9 & 0.62 +/- 0.9 pre- and post
      operatively respectively). Corneal clarity improved in 13 eyes (76.5 %) in the
      PTB group, while three eyes (12 %) had worsened in the T group. Total cumulative
      chances for success were 88.2 % (15 out of 17 eyes), compared to 56 % (14 out of
      25 eyes), in the PTB and T groups, respectively (p = 0.027). CONCLUSIONS: PTB is
      a promising surgical technique for the control of primary congenital glaucoma. A
      randomized controlled trial with a longer follow-up is recommended.

PMID- 24687148
TI  - On Hokusai's Great wave off Kanagawa: localization, linearity and a rogue wave in
      sub-Antarctic waters.
AB  - The Hokusai woodcut entitled The great wave off Kanagawa has been interpreted as
      an unusually large storm wave, likely to be classed as a rogue wave, and possibly
      generated from nonlinear wave dynamics (J. H. E. Cartwright and H. Nakamura,
      Notes Rec. R. Soc.63, 119-135 (2009)). In this paper, we present a complementary
      discussion of this hypothesis, discussing in particular how linear and nonlinear
      mechanisms can both contribute to the emergence of rogue wave events. By making
      reference to the Great wave's simultaneous transverse and longitudinal
      localization, we show that the purely linear mechanism of directional focusing
      also predicts characteristics consistent with those of the Great wave. In
      addition, we discuss the properties of a particular rogue wave photographed on
      the open ocean in sub-Antarctic waters, which shows two-dimensional localization
      and breaking dynamics remarkably similar to Hokusai's depiction in the woodcut.

PMID- 24687147
TI  - Safety behaviors and speech treatment for adults who stutter.
AB  - PURPOSE: Those with anxiety use safety behaviors when attempting to prevent
      negative outcomes. There is evidence that these behaviors contribute to the
      persistence of anxiety disorders. Safety behaviors have been prominent in the
      cognitive behavior therapy literature during the last decade, particularly with
      social phobia management. However, nothing is known of safety behavior use by
      those who stutter. This is surprising given the high prevalence of social phobia
      in the stuttering population who seek clinical help. METHOD: Clinical
      psychologists and speech-language pathologists (SLPs) created a list of safety
      behaviors that might be used by adults during treatment for stuttering.
      Participants were 160 SLPs who were asked whether they advised adults who stutter
      to use any of these safety behaviors. RESULTS: SLPs commonly recommend safety
      behaviors during stuttering management. Factor structures were found for the
      following 5 safety behavior categories: (a) general safety behaviors, (b)
      practice and rehearsal, (c) general avoidance, (d) choosing safe and easy people,
      and (e) control-related safety behaviors. CONCLUSIONS: There is a need to
      determine the frequency with which adults who receive stuttering treatment follow
      these clinician recommendations. In addition, there is a need to experimentally
      determine whether following such recommendations prevents fear extinction at long
      term follow-up.

PMID- 24687146
TI  - Sleep and circadian rhythm regulation in early Parkinson disease.
AB  - IMPORTANCE: Sleep disturbances are recognized as a common nonmotor complaint in
      Parkinson disease but their etiology is poorly understood. OBJECTIVE: To define
      the sleep and circadian phenotype of patients with early-stage Parkinson disease.
      DESIGN, SETTING, AND PARTICIPANTS: Initial assessment of sleep characteristics in
      a large population-representative incident Parkinson disease cohort (N=239) at
      the University of Cambridge, England, followed by further comprehensive case
      control sleep assessments in a subgroup of these patients (n=30) and matched
      controls (n=15). MAIN OUTCOMES AND MEASURES: Sleep diagnoses and sleep
      architecture based on polysomnography studies, actigraphy assessment, and 24-hour
      analyses of serum cortisol, melatonin, and peripheral clock gene expression
      (Bmal1, Per2, and Rev-Erbalpha). RESULTS: Subjective sleep complaints were
      present in almost half of newly diagnosed patients and correlated significantly
      with poorer quality of life. Patients with Parkinson disease exhibited increased
      sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid
      eye movement sleep (P = .02). In addition, there was a sustained elevation of
      serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1
      expression in patients with Parkinson disease compared with controls. CONCLUSIONS
      AND RELEVANCE: Sleep dysfunction seen in early Parkinson disease may reflect a
      more fundamental pathology in the molecular clock underlying circadian rhythms.

PMID- 24687149
TI  - Recent developments and applications of electron transfer dissociation mass
      spectrometry in proteomics.
AB  - Electron transfer dissociation (ETD) has been developed recently as an efficient
      ion fragmentation technique in mass spectrometry (MS), being presently considered
      a step forward in proteomics with real perspectives for improvement, upgrade and
      application. Available also on affordable ion trap mass spectrometers, ETD
      induces specific N-Calpha bond cleavages of the peptide backbone with the
      preservation of the post-translational modifications and generation of product
      ions that are diagnostic for the modification site(s). In addition, in the last
      few years ETD contributed significantly to the development of top-down approaches
      which enable tandem MS of intact protein ions. The present review, covering the
      last 5 years highlights concisely the major achievements and the current
      applications of ETD fragmentation technique in proteomics. An ample part of the
      review is dedicated to ETD contribution in the elucidation of the most common
      posttranslational modifications, such as phosphorylation and glycosylation.
      Further, a brief section is devoted to top-down by ETD method applied to intact
      proteins. As the last few years have witnessed a major expansion of the
      microfluidics systems, a few considerations on ETD in combination with chip-based
      nanoelectrospray (nanoESI) as a platform for high throughput top-down proteomics
      are also presented.

PMID- 24687150
TI  - The role of radiation therapy after nipple-sparing mastectomy.
AB  - PURPOSE: The aim of this review was to examine the incidence of nipple-areola
      complex (NAC) involvement, the rates of NAC recurrence, and the data regarding
      the role of radiation therapy (RT) following nipple-sparing mastectomy (NSM).
      METHODS: A literature review was performed using the PubMed search engine, with
      articles selected based on standardized criteria. Additional articles included
      those known to the authors and those obtained by review of references from key
      studies. RESULTS: The reported incidence of NAC involvement ranges from 0 to 58
      %. The most commonly associated factors with NAC involvement include tumor-to-NAC
      distance, tumor size, central location of the primary tumor,
      multicentricity/multifocality, and positive axillary lymph nodes. Following NSM,
      in the setting of proper patient selection, rates of NAC recurrence are generally
      low, with the majority of studies reporting rates ranging from 0 to 4 %. There is
      a paucity of data evaluating the role of RT after NSM and a lack of level I
      evidence, with the largest series documenting low rates of local recurrence with
      RT but failing to provide a control arm without radiotherapy. CONCLUSIONS:
      Optimal preoperative patient selection for NSM and intraoperative assessment of
      the NAC result in acceptably low rates of NAC involvement/recurrence. NSM alone
      is not adequate justification for post-mastectomy radiation. NSM should be taken
      into consideration to inform radiation decision making only when preoperative
      imaging, clinical features, or pathologic findings suggest higher risk for NAC
      involvement.

PMID- 24687151
TI  - Systematic review and meta-analysis comparing the surgical outcomes of invasive
      intraductal papillary mucinous neoplasms and conventional pancreatic ductal
      adenocarcinoma.
AB  - OBJECTIVE: The aim of this study was to summarize the current literature
      comparing the surgical outcomes of invasive intraductal papillary mucinous
      neoplasms (IPMN(INV)) and conventional pancreatic ductal adenocarcinomas (PDAC)
      in order to determine the differences in disease characteristics and prognosis.
      METHODS: Systematic review of the literature yielded 12 comparative studies
      reporting the clinicopathological characteristics and overall survival (OS) of
      1,450 patients with IPMN(INV) with 19,304 patients with conventional PDAC.
      RESULTS: IPMN(INV) had a significantly lower likelihood of tumors extending
      beyond the pancreas [27.6 vs. 94.3 %; T4 vs. T1: odds ratio (OR) 0.111, 95 %
      confidence intervals (CI) 0.057-0.214], nodal metastasis (45.4 vs. 62.9 %: OR
      0.507, 95 % CI 0.347-0.741), positive margin (14.2 vs. 28.3 %; OR 0.438, 95 % CI
      0.322-0.596), perineural invasion (49.2 vs. 76.5 %; OR 0.304, 95 % CI 0.106
      0.877) and vascular invasion (25.2 vs. 45.7 % OR 0.417, 95 % CI 0.177-0.980) when
      compared with PDAC. The 5-year OS of IPMN(INV) was significantly better than PDAC
      [31.4 vs. 12.4 %: hazard ratio (HR) 0.659, 95 % CI 0.574-0.756]. The tubular
      subtype had a poorer 5-year OS and demonstrated significantly more aggressive
      features such as nodal metastases, vascular invasion, and perineural invasion
      compared with the colloid subtype. CONCLUSION: IPMN(INV) were significantly more
      likely to present at an earlier stage and were less likely to demonstrate nodal
      involvement, perineural invasion and vascular invasion. When controlled for
      stage, IPMN(INV) had an improved OS when compared with PDAC in the early stages.

PMID- 24687152
TI  - Risk factors and learning curve associated with postoperative morbidity of
      laparoscopic total gastrectomy for gastric carcinoma.
AB  - BACKGROUND: Laparoscopic total gastrectomy (LTG) is a challenging surgical
      procedure that has substantial technical difficulties and complications. In this
      study, we investigated risk factors for morbidity and mortality after LTG, and
      the learning curve associated with postoperative morbidity. METHODS:
      Prospectively constructed data of 203 patients undergoing LTG between 2004 and
      2013 were retrospectively reviewed. The multivariate logistic regression model
      was used to analyze risk factors for postoperative morbidity. The Cumulative Sum
      (CUSUM) technique was used to assess the learning curve. RESULTS: Postoperative
      morbidity and mortality after LTG was 18.7 and 1.5 %, respectively. Of 38
      patients with postoperative morbidity, 7 (3.4 %) were managed with reoperation, 8
      (4.0 %) with radiologic or endoscopic intervention, and 23 (11.3 %) with a
      conservative treatment. Of local complications, gastrointestinal bleeding was the
      most common (12 patients), followed by anastomosis leakage (9 patients) and intra
      abdominal abscess (9 patients). Respiratory complication was the most common of
      the systemic complications. There were 17 cases (8.4 %) of complications
      exceeding grade III severity, of which anastomosis leakage was the most common.
      CUSUM analysis showed that postoperative morbidity reached a plateau after around
      45 cases. Univariate and multivariate analyses revealed that old age (over 65
      years of age) and surgical experience (<45 cases) were independent factors for
      postoperative morbidity after LTG. CONCLUSION: LTG is a feasible technique with
      acceptable morbidity and mortality. However, substantial surgical experience is
      of most importance to reduce postoperative morbidity and mortality.

PMID- 24687153
TI  - Diagnostic value of computed tomography for staging of clinical T1 gastric
      cancer.
AB  - BACKGROUND: T1 gastric cancer can be diagnosed only by endoscopy and is almost
      curable by local treatment. It has been unclear how a multidetector-row computed
      tomography (CT) evaluation is valuable for clinical T1 patients. METHODS:
      Patients with clinical T1 disease, as diagnosed by endoscopy and treated with
      endoscopic submucosal dissection (ESD) or surgery between October 2000 and
      October 2007, were examined. The efficacy of CT was evaluated by the reversal
      rate of endoscopic T1 by CT, the incidence of clinical M1 disease, and the
      accuracy of diagnosing pathological N+ disease in patients who received surgery.
      To confirm metachronous distant and nodal metastases, the disease-free survival
      (DFS) also was evaluated. RESULTS: A total of 761 patients, 236 treated by ESD
      and 525 treated with surgery, were examined. None of the patients had an
      endoscopic diagnosis of clinical T1 reversed by CT. No clinical M1 disease was
      found. Among the 525 patients who underwent surgery, 8 showed clinical N+ disease
      (1.5 %), while 47 demonstrated pathological N+ disease (8.9 %). The accuracy,
      sensitivity, specificity, positive predictive value, and negative predictive
      values were 90.3, 4.3, 98.7, 25, and 91.3 %, respectively. The 5-year DFS rate
      was 93.6 % (95 % confidence interval 91.4-95.8 %). CONCLUSIONS: The present study
      suggests that diagnostic value of CT is limited for staging of clinical T1
      gastric cancer patients, because the reversal rate of endoscopic T1 by CT was
      very low, clinical M1 disease was rare, the diagnosis of N+ status was
      unreliable, and metachronous M1 and N+ findings were rare.

PMID- 24687154
TI  - A High-Throughput Assay to Identify Inhibitors of the Apicoplast DNA Polymerase
      from Plasmodium falciparum.
AB  - Infection by Plasmodium falciparum is the leading cause of malaria in humans. The
      parasite contains a unique and essential plastid-like organelle called the
      apicoplast that, similar to the mitochondria and chloroplast, houses its own
      genome that must undergo replication and repair. The putative apicoplast
      replicative DNA polymerase, POM1, has no direct orthologs in mammals, making the
      P. falciparum POM1 an attractive antimalarial drug target. Here, we report on a
      fluorescent high-throughput DNA polymerase assay that relies on the ability of
      POM1 to perform strand-displacement synthesis through the stem of a DNA hairpin
      substrate, thereby separating a Cy3 dye from a quencher. Assay-validation
      experiments were performed using 384-well plates and resulted in a signal window
      of 7.90 and aZ' factor of 0.71. A pilot screen of a 2880-compound library
      identified 62 possible inhibitors that cause more than 50% inhibition of
      polymerase activity. The simplicity and statistical robustness of the assay
      suggest it is well suited for the screening of novel apicoplast polymerase
      inhibitors that may serve as lead compounds in antimalarial drug-discovery
      efforts.

PMID- 24687155
TI  - Heterogeneous Antibody-Based Activity Assay for Lysine Specific Demethylase 1
      (LSD1) on a Histone Peptide Substrate.
AB  - Posttranslational modifications of histone tails are very important for
      epigenetic gene regulation. The lysine-specific demethylase LSD1 (KDM1A/AOF2)
      demethylates in vitro predominantly mono- and dimethylated lysine 4 on histone 3
      (H3K4) and is a promising target for drug discovery. We report a heterogeneous
      antibody-based assay, using dissociation-enhanced lanthanide fluorescent
      immunoassay (DELFIA) for the detection of LSD1 activity. We used a biotinylated
      histone 3 peptide (amino acids 1-21) with monomethylated lysine 4 (H3K4me) as the
      substrate for the detection of LSD1 activity with antibody-mediated quantitation
      of the demethylated product. We have successfully used the assay to measure the
      potency of reference inhibitors. The advantage of the heterogeneous format is
      shown with cumarin-based LSD1 inhibitor candidates that we have identified using
      virtual screening. They had shown good potency in an established LSD1 screening
      assay. The new heterogeneous assay identified them as false positives, which was
      verified using mass spectrometry.

PMID- 24687156
TI  - Two-year outcome of a randomized trial comparing second-generation drug-eluting
      stents using biodegradable or durable polymer.

PMID- 24687158
TI  - A robust, catalytic metal-organic framework with open 2,2'-bipyridine sites.
AB  - We report two synthetic approaches to prepare a highly crystalline Zr(IV)-based
      metal-organic framework (MOF) containing open 2,2'-bipyridine (bpy) chelating
      sites. The resulting UiO-67-bpydc readily forms complexes with PdCl2 to produce a
      MOF that exhibits efficient and recyclable catalytic activity for the Suzuki
      Miyaura cross-coupling reaction.

PMID- 24687159
TI  - Description of an intensive residential aphasia treatment program: rationale,
      clinical processes, and outcomes.
AB  - PURPOSE: The purpose of this article is to describe the rationale, clinical
      processes, and outcomes of an intensive comprehensive aphasia program (ICAP).
      METHOD: Seventy-three community-dwelling adults with aphasia completed a
      residentially based ICAP. Participants received 5 hr of daily 1:1 evidence-based
      cognitive-linguistically oriented aphasia therapy, supplemented with weekly
      socially oriented and therapeutic group activities over a 23-day treatment
      course. Standardized measures of aphasia severity and communicative functioning
      were obtained at baseline, program entry, program exit, and follow-up. Results
      were analyzed using a Bayesian latent growth curve model with 2 factors
      representing (a) the initial level and (b) change over time, respectively, for
      each outcome measure. RESULTS: Model parameter estimates showed reliable
      improvement on all outcome measures between the initial and final assessments.
      Improvement during the treatment interval was greater than change observed across
      the baseline interval, and gains were maintained at follow-up on all measures.
      CONCLUSIONS: The rationale, clinical processes, and outcomes of a residentially
      based ICAP have been described. ICAPs differ with respect to treatments
      delivered, dosing parameters, and outcomes measured. Specifying the defining
      components of complex interventions, establishing their feasibility, and
      describing their outcomes are necessary to guide the development of controlled
      clinical trials.

PMID- 24687160
TI  - Environmental enrichment alters splenic immune cell composition and enhances
      secondary influenza vaccine responses in mice.
AB  - Chronic stress has deleterious effects on immune function, which can lead to
      adverse health outcomes. However, studies investigating the impact of stress
      reduction interventions on immunity in clinical research have yielded divergent
      results, potentially stemming from differences in study design and genetic
      heterogeneity, among other clinical research challenges. To test the hypothesis
      that reducing glucocorticoid levels enhances certain immune functions, we
      administered influenza vaccine once (prime) or twice (boost) to mice housed in
      either standard control caging or environmental enrichment (EE) caging. We have
      shown that this approach reduces mouse corticosterone production. Compared with
      controls, EE mice had significantly lower levels of fecal corticosterone
      metabolites (FCMs) and increased splenic B and T lymphocyte numbers.
      Corticosterone levels were negatively associated with the numbers of CD19(+)
      (r(2) = 0.43, p = 0.0017), CD4(+) (r(2) = 0.28, p = 0.0154) and CD8(+) cells
      (r(2) = 0.20, p = 0.0503). Vaccinated mice showed nonsignificant differences in
      immunoglobulin G (IgG) titer between caging groups, although EE mice tended to
      exhibit larger increases in titer from prime to boost than controls; the
      interaction between the caging group (control versus EE) and vaccine group (prime
      versus boost) showed a strong statistical trend (cage-group*vaccine-group, F =
      4.27, p = 0.0555), suggesting that there may be distinct effects of EE caging on
      primary versus secondary IgG vaccine responses. Vaccine-stimulated splenocytes
      from boosted EE mice had a significantly greater frequency of interleukin 5 (IL
      5)-secreting cells than boosted controls (mean difference 7.7, IL-5 spot-forming
      units/10(6) splenocytes, 95% confidence interval 0.24-135.1, p = 0.0493) and
      showed a greater increase in the frequency of IL-5-secreting cells from prime to
      boost. Our results suggest that corticosterone reduction via EE caging was
      associated with enhanced secondary vaccine responses, but had little effect on
      primary responses in mice. These findings help identify differences in primary
      and secondary vaccine responses in relationship to stress mediators that may be
      relevant in clinical studies. 

PMID- 24687161
TI  - Using informative verbal exchanges to promote verb retrieval in nonfluent
      aphasia.
AB  - PURPOSE: The goal of this study was to determine whether positive treatment
      effects of a modified constraint-induced language therapy focused on verb
      production would generalize to unpracticed items and tasks. METHOD: Four
      individuals participated in a single-subject treatment design protocol. The
      treatment involved intensive practice producing verbs in sentences in an
      informative communicative exchange. Direct treatment outcome was examined by
      measuring the accuracy of producing practiced verbs in an action description
      task, a task similar to those used in treatment. Generalization was assessed by
      measuring production of unpracticed verbs and sentence grammaticality in the
      action description task and by measuring verb production and sentence
      grammaticality in 2 relatively unstructured (unpracticed) language tasks.
      RESULTS: Two of the 4 participants showed a direct treatment effect, producing a
      greater number of practiced verbs in the action description task following
      treatment compared with before treatment. All participants improved sentence
      grammaticality following treatment, although grammaticality was not explicitly
      targeted in therapy. Generalization to unpracticed, less-structured tasks was
      variable across the participants. CONCLUSION: Patterns of generalization may
      depend on participants' specific language deficits and production
      characteristics, on the language tasks used, and on the measures used to detect
      change and assess generalization.

PMID- 24687162
TI  - Absolute and relative reliability of percentage of syllables stuttered and
      severity rating scales.
AB  - PURPOSE: Percentage of syllables stuttered (%SS) and severity rating (SR) scales
      are measures in common use to quantify stuttering severity and its changes during
      basic and clinical research conditions. However, their reliability has not been
      assessed with indices measuring both relative and absolute reliability. This
      study was designed to provide such information. Relative reliability deals with
      the rank order of participants in a sample, whereas absolute reliability measures
      the closeness of scores to one other and to a hypothetical true score. METHOD:
      Eighty-seven adult participants who stutter received a 10-min unscheduled
      telephone call. Three experienced judges measured %SS and also used a 9-point SR
      scale to measure stuttering severity from recordings of the telephone calls.
      RESULTS: Relative intrajudge and interjudge reliability were satisfactory for
      both scales. However, absolute intrajudge and interjudge reliability were not
      satisfactory. Results showed that paired-judge SR and %SS procedures improved
      absolute reliability compared with single-judge measures. Additionally, the
      paired-judge procedure improved relative reliability from high to very high
      levels. CONCLUSION: Measurement of group changes of stuttering severity can be
      done in research contexts using either %SS or SR. However, for detecting changes
      within individuals using such measures, a paired-judge procedure is a more
      reliable method.

PMID- 24687163
TI  - UK hospital drops partnership plans after quality of care improves.

PMID- 24687164
TI  - Falsely elevated plasma selenium due to gadolinium contrast interference: a novel
      solution to a preanalytical problem.
AB  - BACKGROUND: Trace elements are commonly measured by inductively coupled mass
      spectrometry (ICP-MS). A 30-year-old man had a plasma selenium (Se) concentration
      on ICP-MS of 66 umol/L (reference interval 0.45-1.40), a potentially lethal
      level, despite no history of Se exposure or toxicity symptoms. He had earlier
      undergone magnetic resonance imaging with a gadolinium (Gd) contrast agent, which
      is known to interfere with Se on ICP-MS. We aimed to adjust our method by
      monitoring a second Se isotope that is unaffected by Gd to detect this
      preanalytical interference. METHODS: Plasma samples referred for trace metal
      testing had Se measured on ICP-MS (monitoring (78)Se), which we modified to also
      monitor a second isotope ((82)Se). The modified method was then applied to a
      specimen with known Gd contamination. RESULTS: Plasma Se results (n = 41) derived
      from monitoring the two different Se isotopes were similar with a good
      correlation (R (2 )= 0.991) over a range of 0.23-2.21 umol/L. On repeat analysis,
      our patient had a Se concentration of 65 umol/L using the (78)Se isotope but only
      1.43 umol/L using (82)Se. CONCLUSION: To avoid reporting a falsely elevated
      plasma Se result, we suggest that Se analysis by ICP-MS should include a second
      Se isotope for monitoring, that is not subject to Gd interference.

PMID- 24687167
TI  - The relative effect of coping strategy and depression on health-related quality
      of life in patients in the chronic phase after stroke.
AB  - OBJECTIVE: To investigate the relative associations of coping strategy and
      depression on health-related quality of life in patients in the chronic phase
      after stroke. DESIGN: Cross-sectional study. SUBJECTS: A total of 213 patients
      after stroke (> 18 months post-onset), mean age 59 years (standard deviation (SD)
      9.86 years), 56% men, mean time post-stroke 53 months (SD 37.8 months). METHODS:
      Coping strategy was measured using the assimilative-accommodative coping scale,
      depression using the Center for Epidemiologic Studies Depression Scale, and
      quality of life using the World Health Organization Quality of Life-BREF.
      Multivariable regression analyses were performed, adjusted for patient
      characteristics. RESULTS: Depression score was independently related to all
      domains of quality of life (Psychological Health (B = -0.924; p = 0.000),
      Physical Health (B = -0.832; p = 0.000), Social Relationships (B = -0.917; p =
      0.000), Environment (B = -0.662, p = 0.000)). Accommodative coping (B = 0.305; p
      = 0.024) and assimilative coping (B = 0.235; p = 0.070) were independently
      related to the domain Psychological Health, adjusted for depression and education
      level. CONCLUSION: Coping strategies and depression score were independently
      associated with Psychological Health in patients in the chronic phase after
      stroke. Patients who prefer an accommodative coping strategy may show less
      symptoms of depression. Preferable coping strategies may be trained in order to
      improve both depression score and health-related quality of life in future
      research.

PMID- 24687165
TI  - Arterial stiffness and beta-amyloid progression in nondemented elderly adults.
AB  - IMPORTANCE: Recent studies show that cerebral beta-amyloid (Abeta) deposition is
      associated with blood pressure and measures of arterial stiffness in nondemented
      individuals. OBJECTIVE: To examine the association between measures of arterial
      stiffness and change in Abeta deposition over time. DESIGN, SETTING, AND
      PARTICIPANTS: Deposition of Abeta was determined in a longitudinal observational
      study of aging by positron emission tomography using the Pittsburgh compound B
      twice 2 years apart in 81 nondemented individuals 83 years and older. Arterial
      stiffness was measured with a noninvasive and automated waveform analyzer at the
      time closest to the second positron emission tomography scan. All measures were
      performed under standardized conditions. Pulse wave velocity (PWV) was measured
      in the central (carotid-femoral and heart-femoral PWV), peripheral (femoral-ankle
      PWV), and mixed (brachial-ankle PWV) vascular beds. MAIN OUTCOMES AND MEASURES:
      The change in Abeta deposition over 2 years was calculated from the 81
      individuals with repeat Abeta-positron emission tomography. RESULTS: The
      proportion of Abeta-positive individuals increased from 48% at baseline to 75% at
      follow-up. Brachial-ankle PWV was significantly higher among Abeta-positive
      participants at baseline and follow-up. Femoral-ankle PWV was only higher among
      Abeta-positive participants at follow-up. Measures of central stiffness and blood
      pressure were not associated with Abeta status at baseline or follow-up, but
      central stiffness was associated with a change in Abeta deposition over time.
      Each standard deviation increase in central stiffness (carotid-femoral PWV, P =
      .001; heart-femoral PWV, P = .004) was linked with increases in Abeta deposition
      over 2 years. CONCLUSIONS AND RELEVANCE: This study showed that Abeta deposition
      increases with age in nondemented individuals and that arterial stiffness is
      strongly associated with the progressive deposition of Abeta in the brain,
      especially in this age group. The association between Abeta deposition changes
      over time and generalized arterial stiffness indicated a relationship between the
      severity of subclinical vascular disease and progressive cerebral Abeta
      deposition.

PMID- 24687168
TI  - Maternal bonding in mothers with postpartum anxiety disorder: the crucial role of
      subclinical depressive symptoms and maternal avoidance behaviour.
AB  - Hardly any research has examined the link between postpartum anxiety disorder and
      maternal bonding. This study examined if postpartum anxiety disorder and maternal
      bonding are related in the postpartum period. Thereby, subclinical depressive
      symptoms and specific aspects of an anxious symptomatology were also taken into
      consideration. The German sample of N = 78 mother-infant dyads is composed of n =
      30 mothers with postpartum anxiety disorders but without major or minor
      depression according to the Diagnostic and Statistical Manual of Mental Disorders
      IV (DSM-IV) and n = 48 healthy mothers. Subjects were interviewed with the
      Structured Clinical Interview for DSM-IV Disorders at an average infant age of M
      = 4.1 months. Moreover, mothers filled out the Postpartum Bonding Questionnaire
      16. The Anxiety Cognitions Questionnaire, the Body Sensations Questionnaire and
      the Mobility Inventory were chosen to assess different aspects of anxious
      symptomatology. To control for concurrent subclinical depressive symptoms, we
      used the German Edinburgh-Postnatal-Depression Scale. Mothers with postpartum
      anxiety disorder reported significantly lower bonding than healthy mothers.
      However, in a linear regression analysis, concurrent subclinical depressive
      symptoms and avoidance of anxiety-related situations in company explained 27 % of
      the overall variance in maternal bonding. The perceived lower bonding of mothers
      with anxiety disorder could be due to aspects of a concurrent subclinical
      depressive symptomatology. This notion emphasizes the need to target even mild
      depressive symptoms in the treatment of postpartum anxiety disorders. The
      outcomes also underline that the severity of anxious symptomatology, reflected by
      avoidance behaviour in company, puts the mother-infant bond at risk.

PMID- 24687170
TI  - A neuron-inspired computational architecture for spatiotemporal visual
      processing: real-time visual sensory integration for humanoid robots.
AB  - In this article, we present a neurologically motivated computational architecture
      for visual information processing. The computational architecture's focus lies in
      multiple strategies: hierarchical processing, parallel and concurrent processing,
      and modularity. The architecture is modular and expandable in both hardware and
      software, so that it can also cope with multisensory integrations - making it an
      ideal tool for validating and applying computational neuroscience models in real
      time under real-world conditions. We apply our architecture in real time to
      validate a long-standing biologically inspired visual object recognition model,
      HMAX. In this context, the overall aim is to supply a humanoid robot with the
      ability to perceive and understand its environment with a focus on the active
      aspect of real-time spatiotemporal visual processing. We show that our approach
      is capable of simulating information processing in the visual cortex in real time
      and that our entropy-adaptive modification of HMAX has a higher efficiency and
      classification performance than the standard model (up to ~+6%).

PMID- 24687171
TI  - Complexation of alkyl groups and ghrelin in a deep, water-soluble cavitand.
AB  - A cavitand with ionic, but nonionizable "feet" folds around hydrophobic guests in
      D2O. Short alkanes and ibuprofen are included and exchange rates are slow on the
      NMR timescale. Normal octanoyl groups show good affinity for the cavitand and the
      gastric peptide ghrelin is bound at low pH and physiological temperature. 

PMID- 24687169
TI  - Effect of metformin on left ventricular function after acute myocardial
      infarction in patients without diabetes: the GIPS-III randomized clinical trial.
AB  - IMPORTANCE: Metformin treatment is associated with improved outcome after
      myocardial infarction in patients with diabetes. In animal experimental studies
      metformin preserves left ventricular function. OBJECTIVE: To evaluate the effect
      of metformin treatment on preservation of left ventricular function in patients
      without diabetes presenting with ST-segment elevation myocardial infarction
      (STEMI). DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled
      study conducted among 380 patients who underwent primary percutaneous coronary
      intervention (PCI) for STEMI at the University Medical Center Groningen, The
      Netherlands, between January 1, 2011, and May 26, 2013. INTERVENTIONS: Metformin
      hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.
      MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular
      ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging.
      A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT
      proBNP) concentration after 4 months. The incidence of major adverse cardiac
      events (MACE; the combined end point of death, reinfarction, or target-lesion
      revascularization) was recorded until 4 months as a secondary efficacy measure.
      RESULTS: At 4 months, all patients were alive and none were lost to follow-up.
      LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared
      with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT
      proBNP concentration was 167 ng/L in the metformin group (interquartile range
      [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P =
      .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2
      patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79
      umol/L [IQR, 70-87 umol/L] vs 79 umol/L [IQR, 72-89 umol/L], P = .61) and
      glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15)
      were not significantly different between both groups. No cases of lactic acidosis
      were observed. CONCLUSIONS AND RELEVANCE: Among patients without diabetes
      presenting with STEMI and undergoing primary PCI, the use of metformin compared
      with placebo did not result in improved LVEF after 4 months. The present findings
      do not support the use of metformin in this setting. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01217307.

PMID- 24687172
TI  - Translocator protein 18 kDa negatively regulates inflammation in microglia.
AB  - Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein.
      Although TSPO expression is up-regulated during neuroinflammation, the role of
      TSPO and its signaling mechanisms in regulation of neuroinflammation remains to
      be elucidated at the molecular level. Here we demonstrate that TSPO is a negative
      regulator of neuroinflammation in microglia. Over-expression of TSPO decreased
      production of pro-inflammatory cytokines upon lipopolysaccharide treatment while
      TSPO knock-down had the opposite effect. Anti-inflammatory activity of TSPO is
      also supported by increased expression of alternatively activated M2 stage
      related genes. These data suggest that up-regulation of TSPO level during
      neuroinflammation may be an adaptive response mechanism. We also provide the
      evidence that the repressive activity of TSPO is at least partially mediated by
      the attenuation of NF-kappaB activation. Neurodegenerative diseases are
      characterized by loss of specific subsets of neurons at the particular anatomical
      regions of the central nervous system. Cause of neuronal death is still largely
      unknown, but it is becoming clear that neuroinflammation plays a significant role
      in the pathophysiology of neurodegenerative diseases. Understanding the
      mechanisms underlying the inhibitory effects of TSPO on neuroinflammation can
      contribute to the therapeutic design for neurodegenerative diseases. 

PMID- 24687173
TI  - Reprolysin metalloproteases from Ixodes persulcatus, Rhipicephalus sanguineus and
      Rhipicephalus microplus ticks.
AB  - Metalloproteases (MPs) have been considered essential for blood feeding and other
      physiological functions in several hematophagous animals, including ticks. We
      report the characterization of MP sequences of three important ticks from Asia,
      Africa and America: Ixodes persulcatus (Ip-MPs), Rhipicephalus sanguineus (Rs
      MPs) and R. microplus (BrRm-MPs). Amino acid sequence identity between R.
      microplus and R. sanguineus MPs ranged from 76 to 100 %, and identities among I.
      persulcatus, I. ricinus and I. scapularis MP sequences ranged from 88 to 97 %.
      This high sequence identity and typical functional motifs show that all sequences
      are MPs. The presence of a zinc binding site, a Met-turn and cysteine rich domain
      at the C-terminal region indicates that these proteins belong to the reproplysin
      family of MPs. Differences in amino acid sequences of BrRm-MP1, BrRm-MP2, BrRm
      MP4 and BrRm-MP5 (from Porto Alegre strain ticks) were 6, 2, 7 and 5 %,
      respectively, when compared with sequences deposited in GenBank for the same
      genes from other R. microplus isolates. Analyses of MPs predicted that they have
      various highly antigenic regions. Semi-quantitative RT-PCR analysis revealed the
      presence of transcripts in salivary glands of partially and fully fed female
      ticks. None of these transcripts were observed in males (except BrRm-MP4) and
      eggs. These enzymes may be functional components required during tick feeding to
      manipulate host defenses and support tick hematophagy.

PMID- 24687174
TI  - Positive correlation of trophic level and proportion of sexual taxa of oribatid
      mites (Acari: Oribatida) in alpine soil systems.
AB  - We investigated community structure, trophic ecology (using stable isotope
      ratios; (15)N/(14)N, (13)C/(12)C) and reproductive mode of oribatid mites (Acari,
      Oribatida) along an altitudinal gradient (2,050-2,900 m) in the Central Alps
      (Obergurgl, Austria). We hypothesized that (1) the community structure changes
      with altitude, (2) oribatid mites span over four trophic levels, (3) the
      proportion of sexual taxa increases with altitude, and (4) the proportion of
      sexual taxa increases with trophic level, i.e. is positively correlated with the
      delta(15)N signatures. Oribatid mite community structure changed with altitude
      indicating that oribatid mites occupy different niches at different altitudes.
      Oribatid mites spanned over 12 delta(15)N units, i.e. about four trophic levels,
      which is similar to lowland forest ecosystems. The proportion of sexually
      reproducing taxa increased from 2,050 to 2,900 m suggesting that limited resource
      availability at high altitudes favors sexual reproduction. Sexual taxa more
      frequently occurred higher in the food web indicating that the reproductive mode
      is related to nutrition of oribatid mites. Generally, oribatid mite community
      structure changed from being decomposer dominated at lower altitude to being
      dominated by fungal and lichen feeders, and predators at higher altitude. This
      supports the view that resources from dead organic material become less available
      with increasing altitude forcing species to feed on living resources such as
      fungi, lichens and nematodes. Our findings support the hypothesis that limited
      resource accessibility (at high altitudes) favors sexually reproducing species
      whereas ample resource supply (at lower altitudes) favors parthenogenetic
      species.

PMID- 24687176
TI  - Effects of thermal stress on lipid peroxidation and antioxidant enzyme activities
      of the predatory mite, Neoseiulus cucumeris (Acari: Phytoseiidae).
AB  - Changes in temperature are known to cause a variety of physiological stress
      responses in insects and mites. Thermal stress responses are usually associated
      with the increased generation of reactive oxygen species (ROS), resulting in
      oxidative damage. In this study, we examined the time-related effect (durations
      for 1, 2, 3, and 5 h) of thermal stress conditions-i.e., relatively low (0, 5,
      10, and 15  degrees C) or high (35, 38, 41, and 44  degrees C) temperatures-on
      the activities of antioxidant enzymes including catalase (CAT), superoxide
      dismutase (SOD), peroxidase (POX), glutathione S-transferases (GSTs), and total
      antioxidant capacity (T-AOC) of the predatory mite Neoseiulus cucumeris. Also the
      lipid peroxidation (LPO) levels of the predatory mite were measured under thermal
      stress conditions. The results confirmed that thermal stress results in a
      condition of so-called oxidative stress and the four antioxidant enzymes play an
      important role in combating the accumulation of ROS in N. cucumeris. CAT and POX
      activity changed significantly when the mites were exposed to cold and heat
      shock, respectively. The elevated levels of SOD and GSTs activity, expressed in a
      time-dependent manner, may have an important role in the process of antioxidant
      response to thermal stress. However, the levels of LPO in N. cucumeris were high,
      serving as an important signal that these antioxidant enzyme-based defense
      mechanisms were not always adequate to counteract the surplus ROS. Thus, we
      hypothesize that thermal stress, especially extreme temperatures, may contribute
      much to the generation of ROS in N. cucumeris, and eventually to its death. 

PMID- 24687175
TI  - Hidden in the mangrove forest: the cryptic intertidal mite Carinozetes mangrovi
      sp. nov. (Acari, Oribatida, Selenoribatidae).
AB  - The small archipelago of Bermuda is a geologically young landmass in the Western
      Atlantic Ocean and recently turned out to be inhabited by a number of intertidal
      oribatid mites. One newly described species, Carinozetes bermudensis, showed an
      unusual vast range of habitats like sandy beaches, rocky substrate and mangroves.
      In the present study, 13 Bermudian populations of C. bermudensis were analysed to
      verify species integrity of specimens from different microhabitats. A
      morphometric analysis of 17 continuous variables as well as a molecular genetic
      investigation of the mitochondrial cytochrome oxidase subunit I revealed the
      existence of a new species Carinozetes mangrovi sp. nov., inhabiting exclusively
      intertidal algae growing on mangrove roots. Although both species are
      morphologically nearly identical, the configuration of the genus-specific ventral
      carinae represents a clear diagnostic character. The high genetic divergence of
      approximately 12 % of the cytochrome oxidase subunit I gene sequence between C.
      bermudensis and C. mangrovi sp. nov. suggests that these two species diverged
      before the emergence of the Bermuda islands. Accordingly, both of them are older
      than the geologically young archipelago of Bermuda.

PMID- 24687177
TI  - Stylostome organization in feeding Leptotrombidium larvae (Acariformes:
      Trombiculidae).
AB  - The stylostome of larvae of the trombiculids Leptotrombidium scutellare (Nagayo
      et al.), Leptotrombidium fletcheri (Womersley et Heaslip) and Leptotrombidium
      deliense (Walch) was studied experimentally at different time intervals after
      larval attachment using the histological method. The stylostome of these species
      has the same organization and belongs to the epidermal combined with the mixed
      type, developing more in width than in length. Neither transverse nor conspicuous
      longitudinal layers are present within the stylostome walls, which stain
      predominantly in red with Azan, also showing longitudinal portions with blue
      staining. Larvae tend to attach closely to each other and scabs, consisting of
      the hyperkeratotic epidermal layers fusing with migrating inflammatory cells,
      develop around the attachment sites. The dermis shows inflammatory foci with
      dilated capillaries and inflammatory cells inserting in the connective tissue
      layer underneath the stylostome. The feeding cavity, which is moderately
      expressed, may be found either in the epidermis or in the dermis. It contains
      inflammatory cells and their debris in the liquefied host tissues. The stylostome
      length depends on the character of the attachment site (the thicker epidermis or
      scab the longer the stylostome), and does not directly correspond to the stages
      of larval feeding. Nevertheless, at the 48-h time interval, nearly all attached
      larvae are found to be fully fed and their midgut cells are filled with
      nutritional globules. 

PMID- 24687178
TI  - Identification of the major sex pheromone component of the scale insect,
      Aulacaspis murrayae Takahashi.
AB  - (R)-Solanone was identified as a female-specific compound from aerations of
      virgin females of the scale insect, Aulacaspis murrayae Takahashi. The
      stereochemistry of the insect-produced solanone was confirmed to be (R) by
      comparison with synthesized racemic and chiral standards on a chiral stationary
      phase GC column. In bioassays, males were strongly attracted to a synthesized
      sample of (R)-solanone, demonstrating that this compound is a sex pheromone
      component for this species. 

PMID- 24687179
TI  - Following in their footprints: cuticular hydrocarbons as overwintering
      aggregation site markers in Hippodamia convergens.
AB  - The convergent lady beetle (Hippodamia convergens) forms large overwintering
      aggregations at revisited montane microsites far removed from their summer
      foraging grounds. Although orientation responses to visual and altitudinal
      features of habitat can explain the arrival of migrants at the general
      overwintering macrosite, the role that pheromones play in the accumulation of
      individuals in inconspicuous hibernacula microsites is not fully understood.
      Through two-choice bioassays and gas chromatography and mass spectrometry, we
      found that H. convergens orient towards hydrocarbons previously deposited on
      their walking surfaces by conspecifics. n-Tricosane (C23) is primarily
      responsible for this chemically-mediated orientation. Footprint extracts, as well
      as C23 alone, induce the eventual accumulation in the field of migrant H.
      convergens at artificial hibernacula, confirming their probable role as
      aggregation signals. Aggregations persisted over many days when footprint
      extracts were applied in conjunction with the previously identified 2-isobutyl-3
      methoxypyrazine (IBMP) aggregation pheromone. The C23 hydrocarbon functions as a
      pheromone that interacts with responses to methoxypyrazines to effectively
      mediate formation of persistent aggregations of diapausing conspecifics at
      specific microsites. Also discussed is the potential effect that C23 has as a
      persistent scent marker in establishing the traditional use of hibernacula. 

PMID- 24687181
TI  - Examining the use of spoken dialect indices with African American children in the
      southern United States.
AB  - PURPOSE: To examine the utility of different dialect indices that have been used
      to characterize the Non-Mainstream American English (NMAE) dialect of African
      American children. The relationships among 4 popular dialect indices were
      examined and compared with the results of a standardized tool used to classify
      the language variation of child speakers at 3 different grade levels. METHOD: The
      authors used listener judgment ratings, 2 dialect density measures obtained from
      a narrative sample, a standardized tool (Part 1 of the Diagnostic Evaluation of
      Language Variation-Screener Test [DELV-ST; Seymour, Roper, & deVilliers, 2003]),
      and dialect variation scores (DVAR) obtained from the DELV-ST to characterize 113
      African American children's spoken production of NMAE. RESULTS: Grade-level
      effects on NMAE varied depending on the index used to measure dialect production.
      All of the dialect indices under investigation were related to one another. DELV
      ST classification group effects were present on all but 1 of the indices used to
      capture NMAE. CONCLUSIONS: Newer measures of NMAE, such as the DELV-ST and DVAR
      scores, are comparable to older measures such as dialect density measures and
      listener judgment ratings. Like listener judgment ratings, the DELV-ST and DVAR
      scores offer clinicians and researchers alike a quicker alternative to dialect
      density measures for confirming and quantifying the spoken production of NMAE
      dialect. The present findings confirm that, depending on the type of data
      collected and questions posed, researchers and clinicians alike are able to
      choose from multiple, valid, and reliable measures of non-mainstream dialect use.

PMID- 24687180
TI  - Reductions in C-reactive protein in older adults with type 2 diabetes are related
      to improvements in body composition following a randomized controlled trial of
      resistance training.
AB  - BACKGROUND: Reductions in skeletal muscle mass and increased adiposity are key
      elements in the aging process and in the pathophysiology of several chronic
      diseases. Systemic low grade inflammation associated with obesity has been shown
      to accelerate the age-related decline in skeletal muscle. The aim of this
      investigation was to determine the effects of 12 months of progressive resistance
      training (PRT) on systemic inflammation, and whether reductions in systemic
      inflammation were associated with changes in body composition. We hypothesized
      that reductions in systemic inflammation following 12 months of PRT in older
      adults with type 2 diabetes would be associated with reductions in adiposity and
      increases in skeletal muscle mass. METHODS: Participants (n = 103) were
      randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C
      reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle
      mass and total fat mass were determined using bioelectrical impedance. RESULTS:
      Twelve months of PRT tended to reduce CRP compared to sham exercise (beta = 
      0.25, p = 0.087). Using linear mixed-effects models, the hypothesized
      relationships between body composition adaptations and CRP changes were
      significantly stronger for skeletal muscle mass (p = 0.04) and tended to be
      stronger for total fat mass (p = 0.07) following PRT when compared to sham
      exercise. Using univariate regression models, stratified by group allocation,
      reductions in CRP were associated with increases in skeletal muscle mass (p =
      0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in
      the sham-exercise group (p = 0.87 and p = 0.32, respectively). CONCLUSIONS: We
      have shown for the first time that reductions in systemic inflammation in older
      adults with type 2 diabetes following PRT were associated with increases in
      skeletal muscle mass. Furthermore, reductions in CRP were associated with
      reductions in adiposity, but only when associated with PRT. Lifestyle
      interventions aimed at reducing systemic inflammation in older adults with type 2
      diabetes should therefore incorporate anabolic exercise such as PRT to optimize
      the anti-inflammatory benefits of favorable body composition adaptations.

PMID- 24687182
TI  - A randomized controlled trial of an inference generation strategy intervention
      for adults with high-functioning autism spectrum disorder.
AB  - PURPOSE: The present intervention study investigated the efficacy of the ACT &
      Check Strategy intervention to improve inference generation when reading,
      metacognitive ability, general reading comprehension, and social inference
      ability in adults with high-functioning autism spectrum disorder (HF-ASD).
      METHOD: Twenty-five adults with HF-ASD were randomly assigned to either a
      treatment or a control group. Treatment sessions were conducted in 1-hr sessions,
      twice a week, for a total of 6 weeks. Treatment focused on explicit instruction
      of components of inference generation, categories of inferences, and increasingly
      independent strategy use. RESULTS: The treatment group demonstrated significantly
      superior performance on 1 of 2 measures of inference generation in reading and 1
      measure of metacognitive ability compared with the control group. Significant
      differences between groups were not found on measures of reading comprehension or
      social inference ability. CONCLUSION: These findings suggest that the ACT & Check
      Strategy was effective in improving participants' ability to generate inferences
      in reading and certain metacognitive abilities, but the skills do not appear to
      generalize to other social communication contexts, such as social inference
      generation. This research provides a measure of support for explicitly teaching
      inference generation to address a reading inference deficit in adults with HF
      ASD.

PMID- 24687183
TI  - Population-level evidence for an autoimmune etiology of epilepsy.
AB  - IMPORTANCE: Epilepsy is a debilitating condition, often with neither a known
      etiology nor an effective treatment. Autoimmune mechanisms have been increasingly
      identified. OBJECTIVE: To conduct a population-level study investigating the
      relationship between epilepsy and several common autoimmune diseases. DESIGN,
      SETTING, AND PARTICIPANTS: A retrospective population-based study using claims
      from a nationwide employer-provided health insurance plan in the United States.
      Participants were beneficiaries enrolled between 1999 and 2006 (N = 2 518 034).
      MAIN OUTCOMES AND MEASURES: We examined the relationship between epilepsy and 12
      autoimmune diseases: type 1 diabetes mellitus, psoriasis, rheumatoid arthritis,
      Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis,
      systemic lupus erythematosus, antiphospholipid syndrome, Sjogren syndrome,
      myasthenia gravis, and celiac disease. RESULTS: The risk of epilepsy was
      significantly heightened among patients with autoimmune diseases (odds ratio,
      3.8; 95% CI, 3.6-4.0; P < .001) and was especially pronounced in children (5.2;
      4.1-6.5; P < .001). Elevated risk was consistently observed across all 12
      autoimmune diseases. CONCLUSIONS AND RELEVANCE: Epilepsy and autoimmune disease
      frequently co-occur; patients with either condition should undergo surveillance
      for the other. The potential role of autoimmunity must be given due consideration
      in epilepsy so that we are not overlooking a treatable cause.

PMID- 24687185
TI  - Alpha-arrestins - new players in Notch and GPCR signaling pathways in mammals.
AB  - For many years, beta-arrestins have been known to be involved in G-protein
      coupled receptor (GPCR) desensitization. However, beta-arrestins belong to a
      family of proteins that act as multifunctional scaffolding proteins, in
      particular during trafficking of transmembrane receptors. The arrestin family
      comprises visual arrestins, beta-arrestins and alpha-arrestins. In mammals, the
      functions of the alpha-arrestins are beginning to be elucidated, and they are
      described as versatile adaptors that link GPCRs or the Notch receptor to E3
      ubiquitin ligases and endocytic factors. These alpha-arrestins can act in
      sequence, complementarily or cooperatively with beta-arrestins in trafficking and
      ubiquitylation events. This Commentary will summarize the recent advances in our
      understanding of the functions and properties of these alpha-arrestin proteins in
      comparison to beta-arrestins, and will highlight a new hypothesis linking their
      functional complementarity to their physical interactions. alpha- and beta
      arrestins could form transient and versatile heterodimers that form a bridge
      between cargo and E3 ubiquitin ligases, thus allowing trafficking to proceed. 

PMID- 24687184
TI  - The effect of Massachusetts health reform on 30 day hospital readmissions:
      retrospective analysis of hospital episode statistics.
AB  - OBJECTIVES: To analyse changes in overall readmission rates and disparities in
      such rates, among patients aged 18-64 (those most likely to have been affected by
      reform), using all payer inpatient discharge databases (hospital episode
      statistics) from Massachusetts and two control states (New York and New Jersey).
      DESIGN: Difference in differences analysis to identify the post-reform change,
      adjusted for secular changes unrelated to reform. SETTING: US hospitals in
      Massachusetts, New York, and New Jersey. PARTICIPANTS: Adults aged 18-64 admitted
      for any cause, excluding obstetrical. MAIN OUTCOME MEASURE: Readmissions at 30
      days after an index admission. RESULTS: After adjustment for known confounders,
      including age, sex, comorbidity, hospital ownership, teaching hospital status,
      and nurse to census ratio, the odds of all cause readmission in Massachusetts was
      slightly increased compared with control states post-reform (odds ratio 1.02, 95%
      confidence interval 1.01 to 1.04, P<0.05). Racial and ethnic disparities in all
      cause readmission rates did not change in Massachusetts compared with control
      states. In analyses limited to Massachusetts only, there were minimal overall
      differences in changes in readmission rates between counties with differing
      baseline uninsurance rates, but black people in counties with the highest
      uninsurance rates had decreased odds of readmission (0.91, 0.84 to 1.00) compared
      with black people in counties with lower uninsurance rates. Similarly, white
      people in counties with the highest uninsurance rates had decreased odds of
      readmission (0.96, 0.94 to 0.99) compared with white people in counties with
      lower uninsurance rates. CONCLUSIONS: In the United States, and in Massachusetts
      in particular, extending health insurance coverage alone seems insufficient to
      improve readmission rates. Additional efforts are needed to reduce hospital
      readmissions and disparities in this outcome.

PMID- 24687186
TI  - GSK-3 - at the crossroads of cell death and survival.
AB  - Glycogen synthase kinase 3 (GSK-3) is involved in various signaling pathways
      controlling metabolism, differentiation and immunity, as well as cell death and
      survival. GSK-3 targets transcription factors, regulates the activity of
      metabolic and signaling enzymes, and controls the half-life of proteins by
      earmarking them for degradation. GSK-3 is unique in its mode of substrate
      recognition and the regulation of its kinase activity, which is repressed by pro
      survival phosphoinositide 3-kinase (PI3K)-AKT signaling. In turn, GSK-3 exhibits
      pro-apoptotic functions when the PI3K-AKT pathway is inactive. Nevertheless, as
      GSK-3 is crucially involved in many signaling pathways, its role in cell death
      regulation is not uniform, and in some situations it promotes cell survival. In
      this Commentary, we focus on the various aspects of GSK-3 in the regulation of
      cell death and survival. We discuss the effects of GSK-3 on the regulation of
      proteins of the BCL-2 family, through which GSK-3 exhibits pro-apoptotic
      activity. We also highlight the pro-survival activities of GSK-3, which are
      observed in the context of nuclear factor kappaB (NFkappaB) signaling, and we
      discuss how GSK-3, by impacting on cell death and survival, might play a role in
      diseases such as cancer.

PMID- 24687188
TI  - Prognostic impact of admission blood glucose for all-cause mortality in patients
      with acute coronary syndromes: added value on top of GRACE risk score.
AB  - BACKGROUND: Abnormal glucose metabolism is a predictor of worse outcome after
      acute coronary syndrome (ACS). However, this parameter is not included in risk
      prediction scores, including GRACE risk score. We sought to evaluate whether the
      inclusion of blood glucose at admission in a model with GRACE risk score improves
      risk stratification. METHODS: Study of consecutive patients included in a single
      centre registry of ACS. Our primary endpoint was the occurrence of all-cause
      mortality at one-year follow-up. The ability of the two logistic regression
      models (GRACE risk score alone and in combination with blood glucose) to predict
      death was analysed. Continuous net reclassification improvement (NRI) and
      integrated discrimination improvement (IDI), with corresponding 95% confidence
      intervals (CIs), were also calculated. RESULTS: We included 2099 patients, with a
      mean age of 64 (SD=13) years, 69% males. In our sample, 55.1% presented with ST
      segment elevation ACS and 13.1% in Killip class >= 2. Only 25% were known
      diabetic at admission. In-hospital mortality was 5.8% and 9.7% at one-year follow
      up. The best cut-point for blood glucose was 160 mg/dl (sensitivity 62% and
      specificity 68%), and 35.2% of the patients had increased levels. This group was
      elderly, had more prevalence of cardiovascular risk factors, worse renal function
      and GRACE score as well as more frequently Killip class >=2. Treatment was
      similar in both groups besides less frequent use of clopidogrel in high glycaemic
      patients. The hyperglycaemia group had higher one-year mortality (17.2% vs. 5.6%,
      p<0.001). Moreover, binary blood glucose remained a predictor of death
      independently of the GRACE risk score and the presence of diabetes (odds ratio
      (OR) 1.99, 95% CI 1.40-2.84, p<0.001). The inclusion of blood glucose, as a
      continuous variable, in a logistic regression model with GRACE score, increased
      the area under the ROC curve from 0.80 to 0.82 (p=0.018) as well as the goodness
      of-fit and was associated with an improvement in both the NRI (37%) and the IDI
      (0.021), suggesting effective reclassification. CONCLUSIONS: A blood glucose
      level on admission >= 160 mg/dl is an independent predictor of mortality in
      medium-term follow-up. It offers an incremental predictive value when added to
      the GRACE risk score, although with a modest magnitude of improvement, probably
      due to the high predictive performance of the GRACE risk score alone.

PMID- 24687189
TI  - Prevalence and predictors of poor sleep quality in mild cognitive impairment.
AB  - AIMS: To investigate the prevalence of and contributors to poor sleep quality in
      patients with mild cognitive impairment (MCI). METHODS: Data were collected for
      158 patients meeting the criteria for MCI. Measures included the Pittsburgh Sleep
      Quality Index, Geriatric Depression Scale, and Mini-Mental State Examination.
      Demographic, lifestyle, medication, and substance use data were also collected.
      RESULTS: A total of 63% of patients with MCI demonstrated sleep disturbance, a
      significantly higher rate than that of the controls (44%; chi-square = 8.77; P =
      .003). Depressive symptoms, cognition, antidepressant usage, alcohol consumption,
      age, and education were identified as significant predictors of self-reported
      sleep quality in patients with MCI (R(2) = .327, F 6,145 = 11.729, P < .0001).
      CONCLUSIONS: Sleep disturbance occurs in around two-thirds of patients with MCI.
      Interventions addressing depression, cognition, and substance and medication use
      may improve sleep quality in MCI.

PMID- 24687190
TI  - Interventions for preventing neuropathy caused by cisplatin and related
      compounds.
AB  - BACKGROUND: Cisplatin and several related antineoplastic drugs used to treat many
      types of solid tumours are neurotoxic, and most patients completing a full course
      of cisplatin chemotherapy develop a clinically detectable sensory neuropathy.
      Effective neuroprotective therapies have been sought. OBJECTIVES: To examine the
      efficacy and safety of purported chemoprotective agents to prevent or limit the
      neurotoxicity of cisplatin and related drugs. SEARCH METHODS: On 4 March 2013, we
      searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL,
      MEDLINE, EMBASE, LILACS, and CINAHL Plus for randomised trials designed to
      evaluate neuroprotective agents used to prevent or limit neurotoxicity of
      cisplatin and related drugs among human patients. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) or quasi-RCTs in which the participants
      received chemotherapy with cisplatin or related compounds, with a potential
      chemoprotectant (acetylcysteine, amifostine, adrenocorticotrophic hormone (ACTH),
      BNP7787, calcium and magnesium (Ca/Mg), diethyldithiocarbamate (DDTC),
      glutathione, Org 2766, oxcarbazepine, or vitamin E) compared to placebo, no
      treatment, or other treatments. We considered trials in which participants
      underwent evaluation zero to six months after completing chemotherapy using
      quantitative sensory testing (the primary outcome) or other measures including
      nerve conduction studies or neurological impairment rating using validated scales
      (secondary outcomes). DATA COLLECTION AND ANALYSIS: Two review authors assessed
      each study, extracted the data and reached consensus, according to standard
      Cochrane methodology. MAIN RESULTS: As of 2013, the review includes 29 studies
      describing nine possible chemoprotective agents, as well as description of two
      published meta-analyses. Among these trials, there were sufficient data in some
      instances to combine the results from different studies, most often using data
      from secondary non-quantitative measures. Nine of the studies were newly included
      at this update. Few of the included studies were at a high risk of bias overall,
      although often there was too little information to make an assessment. At least
      two review authors performed a formal review of an additional 44 articles but we
      did not include them in the final review for a variety of reasons.Of seven
      eligible amifostine trials (743 participants in total), one used quantitative
      sensory testing (vibration perception threshold) and demonstrated a favourable
      outcome in terms of amifostine neuroprotection, but the vibration perception
      threshold result was based on data from only 14 participants receiving amifostine
      who completed the post-treatment evaluation and should be regarded with caution.
      Furthermore the change measured was subclinical. None of the three eligible Ca/Mg
      trials (or four trials if a single retrospective study was included) described
      our primary outcome measures. The four Ca/Mg trials included a total of 886
      participants. Of the seven eligible glutathione trials (387 participants), one
      used quantitative sensory testing but reported only qualitative analyses. Four
      eligible Org 2766 trials (311 participants) employed quantitative sensory testing
      but reported disparate results; meta-analyses of three of these trials using
      comparable measures showed no significant vibration perception threshold
      neuroprotection. The remaining trial reported only descriptive analyses.
      Similarly, none of the three eligible vitamin E trials (246 participants)
      reported quantitative sensory testing. The eligible single trials involving
      acetylcysteine (14 participants), diethyldithiocarbamate (195 participants),
      oxcarbazepine (32 participants), and retinoic acid (92 participants) did not
      perform quantitative sensory testing. In all, this review includes data from 2906
      participants. However, only seven trials reported data for the primary outcome
      measure of this review, (quantitative sensory testing) and only nine trials
      reported our objective secondary measure, nerve conduction test results.
      Additionally, methodological heterogeneity precluded pooling of the results in
      most cases. Nonetheless, a larger number of trials reported the results of
      secondary (non-quantitative and subjective) measures such as the National Cancer
      Institute Common Toxicity Criteria (NCI-CTC) for neuropathy (15 trials), and
      these results we pooled and reported as meta-analysis. Amifostine showed a
      significantly reduced risk of developing neurotoxicity NCI-CTC (or equivalent) >=
      2 compared to placebo (RR 0.26, 95% CI 0.11 to 0.61). Glutathione was also
      efficacious with an RR of 0.29 (95% CI 0.10 to 0.85). In three vitamin E studies
      subjective measures not suitable for combination in meta analysis each favoured
      vitamin E. For other interventions the qualitative toxicity measures were either
      negative (N-acetyl cysteine, Ca/Mg, DDTC and retinoic acid) or not evaluated
      (oxcarbazepine and Org 2766).Adverse events were infrequent or not reported for
      most interventions. Amifostine was associated with transient hypotension in 8% to
      62% of participants, retinoic acid with hypocalcaemia in 11%, and approximately
      20% of participantss withdrew from treatment with DDTC because of toxicity.
      AUTHORS' CONCLUSIONS: At present, the data are insufficient to conclude that any
      of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and
      magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxcarbazepine, retinoic
      acid, or vitamin E) prevent or limit the neurotoxicity of platin drugs among
      human patients, as determined using quantitative, objective measures of
      neuropathy. Amifostine, calcium and magnesium, glutathione, and vitamin E showed
      modest but promising (borderline statistically significant) results favouring
      their ability to reduce the neurotoxicity of cisplatin and related
      chemotherapies, as measured using secondary, non-quantitative and subjective
      measures such as the NCI-CTC neuropathy grading scale. Among these interventions,
      the efficacy of only vitamin E was evaluated using quantitative nerve conduction
      studies; the results were negative and did not support the positive findings
      based on the qualitative measures. In summary, the present studies are limited by
      the small number of participants receiving any particular agent, a lack of
      objective measures of neuropathy, and differing results among similar trials,
      which make it impossible to conclude that any of the neuroprotective agents
      tested prevent or limit the neurotoxicity of platinum drugs.

PMID- 24687191
TI  - Treatment of depression: men and women are different?

PMID- 24687192
TI  - Computerization of the therapeutic task of working through.

PMID- 24687193
TI  - Toward personalized medicine in the pharmacotherapy of alcohol use disorder:
      targeting patient genes and patient goals.

PMID- 24687194
TI  - The NIMH Research Domain Criteria (RDoC) Project: precision medicine for
      psychiatry.

PMID- 24687195
TI  - Management of clozapine-induced fever in a child.

PMID- 24687196
TI  - Johann Christian Reil (1759-1813): pioneer of psychiatry, city physician, and
      advocate of public medical care.

PMID- 24687203
TI  - Cognate and noncognate metal ion coordination in metal-specific metallothioneins:
      the Helix pomatia system as a model.
AB  - The Helix pomatia metallothionein (MT) system, namely, its two highly specific
      forms, HpCdMT and HpCuMT, has offered once again an optimum model to study metal
      protein specificity. The present work investigates the most unexplored aspect of
      the coordination behavior of MT polypeptides with respect to either cognate or
      noncognate metal ions, as opposed to the standard studies of cognate metal ion
      coordination. To this end, we analyzed the in vivo synthesis of the corresponding
      complexes with their noncognate metals, and we performed a detailed spectroscopic
      and spectrometric study of the Zn(2+)/Cd(2+) and Zn(2+)/Cu(+) in vitro
      replacement reactions on the initial Zn-HpMT species. An HpCuMTAla site-directed
      mutant, exhibiting differential Cu(+)-binding abilities in vivo, was also
      included in this study. We demonstrate that when an MT binds its cognate metal,
      it yields well-folded complexes of limited stoichiometry, representative of
      minimal-energy conformations. In contrast, the incorporation of noncognate metal
      ions is better attributed to an unspecific reaction of cysteinic thiolate groups
      with metal ions, which is dependent on their concentration in the surrounding
      milieu, where no minimal-energy structure is reached, and otherwise, the MT
      peptide acts as a multidentate ligand that will bind metal ions until its
      capacity has been saturated. Additionally, we suggest that previous binding of an
      MT polypeptide with its noncognate metal ion (e.g., binding of Zn(2+) to the
      HpCuMT isoform) may preclude the correct folding of the complex with its cognate
      metal ion.

PMID- 24687205
TI  - Rasch validation of the Activities-specific Balance Confidence Scale and its
      short versions in patients with Parkinson's disease.
AB  - OBJECTIVE: To analyse in patients with Parkinson's disease the psychometric
      performance of the Activities-specific Balance Confidence scale (ABC) and its 3
      short versions, using both a classical test theory approach and Rasch analysis.
      METHODS: A sample of 217 patients with Parkinson's disease was assessed by ABC
      and the 3 short versions: Berg Balance Scale, Fear of Falling Measure, and the
      Unified Parkinson's Disease Rating Scale. RESULTS: Cronbach's alpha was 0.95 in
      ABC, and ranged from 0.88 to 0.90 in its short versions. At Rasch analysis the 11
      original rating categories were collapsed to 5 levels. In ABC 15 out of 16 items
      fitted the Rasch model. The ABC showed high correlation only with Fear of Falling
      Measure (r = 0.85), and excellent correlation with its short versions (r > 0.93).
      The 3 short versions showed a limited range of item difficulty estimates, low
      reliability levels, floor effect, a mismatch between mean item difficulty and
      mean ability of the patients. CONCLUSION: In patients with Parkinson's disease:
      (i) the ABC has an adequate unidimensionality; (ii) the selection of its items is
      satisfactory, although there is room for some minor refinement; (iii) the 0-10
      rating scale should be simplified, and a 5-level response format seems able to
      improve the measurement qualities of the scale; (iv) the 3 short versions showed
      some psychometric limitations in comparison with the ABC.

PMID- 24687204
TI  - Mechanisms by which calcium receptor stimulation modifies electromechanical
      coupling in isolated ventricular cardiomyocytes.
AB  - The calcium-sensing receptor (CaR) is widely expressed throughout the entire
      cardiovascular system and is capable of activating signaling pathways in
      different cells. Alongside calcium, the CaR also responds to physiological
      polycations such as putrescine underlining a participation in physiological and
      pathophysiological processes. Here, we aimed to determine mechanisms as to how
      CaR activation affects the contractile responsiveness of ventricular
      cardiomyocytes under basal and stimulated conditions. For that purpose, cardiac
      myocytes from 3-month-old male Wistar rats were isolated, and the acute effects
      of an antagonist (NPS2390), agonists (putrescine and gadolinium), or of
      downregulation of the CaR by siRNA on cell shortening were recorded in a cell
      edge-detection system. In addition, experiments were performed on muscle stripes
      and Langendorff preparations. Mechanistic insights were taken from calcium
      transients of beating fura-2 AM-loaded cardiomyocytes and western blots. Isolated
      ventricular cardiomyocytes constitutively express CaR. The expression in the
      atria is less pronounced. Acute inhibition of CaR reduced basal cell shortening
      of ventricular myocytes at nearly physiological levels of extracellular calcium.
      Inhibition of CaR strongly reduced contractility of ventricular muscle stripes
      but not of atria. Activation of CaR by putrescine and gadolinium influences the
      contractile responsiveness of isolated cardiomyocytes. Increased calcium
      mobilization from the sarcoplasmic reticulum via an IP3-dependent mechanism was
      responsible for amplified systolic calcium transients and a subsequent
      improvement in cell shortening. Alongside with these effects, activation of CaR
      increased relaxation velocity of the cells. In conclusion, ventricular CaR
      expression affects contractile parameters of ventricular heart muscle cells and
      modifies electromechanical coupling of cardiomyocytes. 

PMID- 24687206
TI  - Enhancing speech intelligibility: interactions among context, modality, speech
      style, and masker.
AB  - PURPOSE: The authors sought to investigate interactions among intelligibility
      enhancing speech cues (i.e., semantic context, clearly produced speech, and
      visual information) across a range of masking conditions. METHOD: Sentence
      recognition in noise was assessed for 29 normal-hearing listeners. Testing
      included semantically normal and anomalous sentences, conversational and clear
      speaking styles, auditory-only (AO) and audiovisual (AV) presentation modalities,
      and 4 different maskers (2-talker babble, 4-talker babble, 8-talker babble, and
      speech-shaped noise). RESULTS: Semantic context, clear speech, and visual input
      all improved intelligibility but also interacted with one another and with
      masking condition. Semantic context was beneficial across all maskers in AV
      conditions but only in speech-shaped noise in AO conditions. Clear speech
      provided the most benefit for AV speech with semantically anomalous targets.
      Finally, listeners were better able to take advantage of visual information for
      meaningful versus anomalous sentences and for clear versus conversational speech.
      CONCLUSION: Because intelligibility-enhancing cues influence each other and
      depend on masking condition, multiple maskers and enhancement cues should be used
      to accurately assess individuals' speech-in-noise perception.

PMID- 24687207
TI  - Sound production treatment: effects of blocked and random practice.
AB  - PURPOSE: This investigation was designed to further the development of a
      treatment for acquired apraxia of speech (AOS), Sound Production Treatment (SPT),
      by examining the effects of blocked and random practice. METHOD: A multiple
      baseline design across participants and behaviors was used with 6 speakers with
      chronic AOS and aphasia. Accuracy of production of target sounds in treated and
      untreated words produced in probe sessions served as the primary dependent
      variable. Stimulus generalization was also measured to phrase production and
      sentence completion. Participants received SPT applied with blocked presentation
      of treatment words (SPT-blocked) and SPT applied with random presentation of
      treatment words (SPT-random). RESULTS: Increases in accuracy of articulation of
      target sounds in treated words were observed for all participants for both
      conditions of treatment. SPT-random appeared to be associated with better
      maintenance for 2 participants. Generalization to untreated words was positive
      for all participants for SPT-random and SPT-blocked. Stimulus generalization
      effects varied across participants and measurement conditions; patterns of
      generalization did not appear to be associated with treatment condition.
      CONCLUSIONS: There may be an advantage for SPT-random for some speakers with AOS.
      Findings from the nonspeech motor learning literature may not translate directly
      to the treatment of AOS.

PMID- 24687208
TI  - Ligand binding assay critical reagents and their stability: recommendations and
      best practices from the Global Bioanalysis Consortium Harmonization Team.
AB  - The L4 Global Harmonization Team on reagents and their stability focused on the
      management of critical reagents for pharmacokinetic, immunogenicity, and
      biomarker ligand binding assays. Regulatory guidance recognizes that reagents are
      important for ligand binding assays but do not address numerous aspects of
      critical reagent life cycle management. Reagents can be obtained from external
      vendors or developed internally, but regardless of their source, there are
      numerous considerations for their reliable long-term use. The authors have
      identified current best practices and provided recommendations for critical
      reagent lot changes, stability management, and documentation. 

PMID- 24687209
TI  - Role of public standards in the safety and efficacy of biologic medicines.
AB  - In this report, we emphasize the importance of public monographs with reference
      materials, coupled with careful process and change control and attention to GMPs,
      as a means of advancing access to good quality, safe, and effective medicines,
      with emphasis on available and incoming biologic medicines. With adequate control
      of articles covered by a monograph, these public standards can form the basis for
      a global public quality platform that covers reference products, non
      interchangeable reference products, biosimilars, and interchangeable biosimilars.
      Working collaboratively with all stakeholders, new approaches allow these public
      standards to emerge nationally and globally in a timely way. Yet, there are
      increasing limitations in the availability of public standards for biologic
      medicines, which may reverse many decades of progress. Solutions are considered
      in this report. 

PMID- 24687211
TI  - Prevention of pin tract infection with iodine-supported titanium pins.
AB  - BACKGROUND: Pin tract infection is one of the most common complications of
      external fixation. We developed techniques to coat titanium implant surfaces with
      iodine. This study clinically evaluated the infection-preventive effects and
      biological safety of iodine-coated external fixation pins. PATIENTS AND METHODS:
      Iodine-supported pins were placed in 39 limbs of 38 patients. The mean age of the
      patients was 33.6 years. Twenty-six patients were men and 12 were women. In all
      patients, the iodine-coated pins were used to prevent infection. There were 476
      pin insertion sites. Pin sites were classified according to the Checketts
      Otterburn classification (grade 1-6). White blood cells (WBC) and C-reactive
      protein (CRP) were measured pre- and postoperatively in all patients. To confirm
      whether iodine from the implant affected physiological functions, thyroid hormone
      levels in the blood were monitored. The change in the amount of iodine deposited
      in the body over time was calculated by examining the removed pins. RESULTS:
      External fixation was used for a mean duration of 6 months. Grade 1 infection was
      found in 2.5% of patients, and grade 2 infection in 1.1%. There was no patient
      with an infection of grade 3 or higher. Median WBC levels were in the normal
      range, and median CRP levels returned to <0.3 mg/dl within 3 weeks after surgery.
      Abnormalities of thyroid gland function were not detected. The amount of iodine
      was maintained for a long time, with approximately 40% remaining after 1 year.
      CONCLUSIONS: Iodine-supported titanium pins were able to decrease the pin tract
      infection rate and had no impact on thyroid function. These results suggest that
      iodine-coated titanium pins are biologically safe and effective at preventing pin
      tract infections.

PMID- 24687212
TI  - Reossification of osteolytic metastases at the acetabulum following gefitinib and
      multidisciplinary treatment for lung cancer: a case report with autopsy findings.

PMID- 24687210
TI  - In vitro lipolysis data does not adequately predict the in vivo performance of
      lipid-based drug delivery systems containing fenofibrate.
AB  - The present study investigated the utility of in vitro lipolysis performance
      indicators drug solubilization and maximum supersaturation ratio (SR(M)) for
      their predictive use for the in vivo performance in a minipig model. The
      commercial Lipanthyl formulation and a series of LbDDS based on identical self
      nanoemulsifying drug delivery systems (SNEDDS) containing 200 mg of fenofibrate,
      either dissolved or suspended, were subjected to combined gastric (pH 2) and
      intestinal (pH 6.5) in vitro lipolysis. Based on the solubilization profiles and
      SRM the rank-order SNEDDS (75% drug load) > super-SNEDDS (150% drug load,
      dissolved) = SNEDDS suspension (150% drug load, partially suspended) > Lipanthyl
      was established, with an increased likelihood of drug precipitation above SR(M) >
      3. The in vitro performance, however, was not reproduced in vivo in a minipig
      model as the mean plasma concentration over time curves of all LbDDS were
      comparable, independent of the initial physical state of the drug. There was no
      correlation between the area under the solubilization-time curves (AUC(in vitro))
      of the intestinal step and the AUC(in vivo). The study suggests careful
      interpretation of in vitro performance criteria and revision of LbDDS
      optimization towards increased solubilization.

PMID- 24687213
TI  - Transtrochanteric rotational osteotomy combined with intra-articular procedures
      for pigmented villonodular synovitis of the hip.

PMID- 24687214
TI  - Meta-analysis of the cardiovascular outcomes with dipeptidyl peptidase 4
      inhibitors: validation of the current FDA mandate.
AB  - BACKGROUND: Earlier meta-analyses have demonstrated a significant reduction in
      major adverse cardiovascular events (MACE) with dipeptidyl peptidase 4-inhibitor
      (DPPI) use, as compared with placebo or alternative anti-diabetic therapies.
      However, the large phase III/IV trials, namely SAVOR-TIMI 53 and the EXAMINE
      trials, failed to demonstrate any significant differences in MACE between DPPI
      and placebo. We aimed to perform an updated meta-analysis of randomized
      controlled trials (RCTs) to investigate the differences in cardiovascular death,
      myocardial infarction (MI), and stroke between DPPI and placebo/alternative
      agents. METHODS: We searched the MEDLINE, EMBASE, and Cochrane databases for
      relevant phase III/IV RCTs. Unpublished trials with results available on national
      clinical trials registers were also included. RCTs with follow-up duration >=24
      weeks were included if they compared DPPI with placebo or an alternative anti
      diabetic agent. RESULTS: A total of 82 RCTs including 73,678 patients were
      included. We did not observe any significant difference in the pooled odds of
      cardiovascular death, MI, or stroke in the composite DPPI arm as compared with
      the control arm. Similarly, the pooled odds of all-cause death and MACE were
      statistically similar between the two groups. None of the clinical outcomes
      studied demonstrated evidence of statistical heterogeneity or publication bias.
      Due to a larger sample size and a longer duration of follow-up, both SAVOR-TIMI
      53 and EXAMINE trials had a considerably larger contribution to the pooled
      estimates in our meta-analysis, driving the updated pooled estimates towards null
      for all clinical outcomes assessed. CONCLUSIONS: DPPI use was not associated with
      increased incidence of cardiovascular mortality, MI, stroke, or MACE compared
      with placebo or alternative anti-diabetic agents.

PMID- 24687215
TI  - Rhetorics of health citizenship: exploring vernacular critiques of government's
      role in supporting healthy living.
AB  - This article explores how older adults negotiate and partially counter normative
      expectations of "health citizenship" that stress individual responsibility for
      maintaining health and preventing health problems. Based on interviews with 55
      participants in Canada and the U.K. about what healthy living means to them in
      their everyday lives, we examine how the dominant discourse of personal
      responsibility in participants' responses is counterpointed by a more muted, yet
      significant, alternative critical perspective on the relative roles and
      responsibilities of government and citizens in making healthy living possible.
      Drawing on Hauser's (1999) concept of vernacular rhetoric along with recent
      theories of environmental citizenship, we analyze how participants exercise their
      civic-political judgment by using a logic of dissociation to argue that what
      government says about the importance of healthy living is incompatible with what
      government does to support citizens' abilities to eat healthily and live
      actively. By deploying this technique of argumentation to address structural
      political-economic dimensions of healthy living, participants enact, in modest
      ways, an alternative, critical-collective mode of health citizenship that
      complicates and, at least partially, disrupts neoliberal constructions of the
      individually responsible, "good" health citizen. 

PMID- 24687216
TI  - Biotransformation of the flame retardant tetrabromobisphenol-A (TBBPA) by
      freshwater microalgae.
AB  - Tetrabromobisphenol-A (TBBPA) is the most widely used brominated flame retardant.
      However, little is known about its biotransformation by algae in aquatic
      environments. The authors investigated transformations of TBBPA by 6 freshwater
      green microalgae and identified its transformation products. Transformation
      experiments were conducted under axenic conditions in a laboratory for 10 d. The
      results showed that TBBPA could be transformed by the selected microalgae, with
      nearly complete removal by Scenedesmus quadricauda and Coelastrum sphaericum
      following 10-d incubation. Five transformation products were positively
      identified by mass spectrometry: TBBPA sulfate, TBBPA glucoside, sulfated TBBPA
      glucoside, TBBPA monomethyl ether, and tribromobisphenol-A. The mechanisms
      involved in the biotransformation of TBBPA include sulfation, glucosylation, O
      methylation, and debromination, which could be an important step for its further
      degradation. This suggests that microalgae can play an important role in the fate
      of TBBPA in aquatic environments. The present study is the first report on algal
      transformation of TBBPA, and the proposed transformation products could have
      significant environmental implications.

PMID- 24687217
TI  - Supramolecular chirality in self-assembled soft materials: regulation of chiral
      nanostructures and chiral functions.
AB  - Supramolecular chirality, which arises from the nonsymmetric spatial arrangement
      of components in the self-assembly systems, has gained great attention owing to
      its relation to the natural biological structures and the possible new functions
      in advanced materials. During the self-assembling process, both chiral and
      achiral components are possible to form chiral nanostructures. Therefore, it
      becomes an important issue how to fabricate these molecular components into
      chiral nanostructures. Furthermore, once the chiral nanostructure is obtained,
      will it show new functions that simple component molecule could not? In this
      research news, we report our recent development in the regulation of chiral
      nanostructures in soft gels or vesicle materials. We have further developed
      several new functions pertaining to the soft gel materials, which single chiral
      molecules could not perform, such as the chiroptical switch, chiral recognition
      and the asymmetry catalysis. 

PMID- 24687218
TI  - Moving from child advocacy to evidence-based care for digital natives.

PMID- 24687219
TI  - Development of determination of four analytes of Zhi-Shao-San decoction using LC
      MS/MS and its application to comparative pharmacokinetics in normal and irritable
      bowel syndrome rat plasma.
AB  - Zhi-Shao-San (ZSS), a traditional Chinese medicinal prescription, has been
      clinically used for the treatment of irritable bowel syndrome (IBS) for
      centuries. A comparative study was designed and conducted to compare the
      pharmacokinetic differences between paeoniflorin naringin, hesperidin and
      neohesperidin after oral administration of ZSS decoction to normal rats and IBS
      rats induced by acetic acid and restraint stress. Further, an efficient,
      sensitive and selective liquid chromatography/tandem mass spectrometry for the
      simultaneous determination of four analytes of ZSS decoction in rat plasma was
      developed and validated. The validated method was successfully applied to
      comparison of pharmacokinetic profiles of analytes in rat plasma. The results
      showed that the absorptions of naringin, hesperidin and neohesperidin in IBS
      group were all significantly higher than those in normal group and no obvious
      difference was seen for paeoniflorin between the two groups, which is helpful for
      improving clinical therapeutic efficacy and further pharmacological studies of
      ZSS.

PMID- 24687220
TI  - Arabidopsis Bax inhibitor-1 promotes sphingolipid synthesis during cold stress by
      interacting with ceramide-modifying enzymes.
AB  - Bax inhibitor-1 (BI-1) is a widely conserved cell death suppressor localized in
      the endoplasmic reticulum membrane. Our previous results revealed that
      Arabidopsis BI-1 (AtBI-1) interacts with not only Arabidopsis cytochrome b 5
      (Cb5), an electron transfer protein, but also a Cb5-like domain (Cb5LD)
      containing protein, Saccharomyces cerevisiae fatty acid 2-hydroxylase 1, which 2
      hydroxylates sphingolipid fatty acids. We have now found that AtBI-1 binds
      Arabidopsis sphingolipid Delta8 long-chain base (LCB) desaturases AtSLD1 and
      AtSLD2, which are Cb5LD-containing proteins. The expression of both AtBI-1 and
      AtSLD1 was increased by cold exposure. However, different phenotypes were
      observed in response to cold treatment between an atbi-1 mutant and a sld1sld2
      double mutant. To elucidate the reasons behind the difference, we analyzed
      sphingolipids and found that unsaturated LCBs in atbi-1 were not altered compared
      to wild type, whereas almost all LCBs in sld1sld2 were saturated, suggesting that
      AtBI-1 may not be necessary for the desaturation of LCBs. On the other hand, the
      sphingolipid content in wild type increased in response to low temperature,
      whereas total sphingolipid levels in atbi-1 were unaltered. In addition, the
      ceramide-modifying enzymes AtFAH1, sphingolipid base hydroxylase 2 (AtSBH2), acyl
      lipid desaturase 2 (AtADS2) and AtSLD1 were highly expressed under cold stress,
      and all are likely to be related to AtBI-1 function. These findings suggest that
      AtBI-1 contributes to synthesis of sphingolipids during cold stress by
      interacting with AtSLD1, AtFAH1, AtSBH2 and AtADS2. 

PMID- 24687221
TI  - Magnitude Representation and Working Memory Updating in Children With Arithmetic
      and Reading Comprehension Disabilities.
AB  - It has been argued that children with learning disabilities (LD) encounter severe
      problems in working memory (WM) tasks, especially when they need to update
      information stored in their WM. It is not clear, however, to what extent this is
      due to a generally poor updating ability or to a difficulty specific to the
      domain to be processed. To examine this issue, two groups of children with
      arithmetic or reading comprehension LD and a group of typically developing
      children (9 to 10 years old) were assessed using two updating tasks requiring to
      select the smallest numbers or objects presented. The results showed that
      children with an arithmetic disability failed in a number updating task, but not
      in the object updating task. The opposite was true for the group with poor
      reading comprehension, whose performance was worse in the object than in the
      number updating task. It may be concluded that the problem of WM updating in
      children with LD is also due to a poor representation of the material to be
      updated. In addition, our findings suggest that the mental representation of the
      size of objects relates to the semantic representation of the objects' properties
      and differs from the quantitative representation of numbers. 

PMID- 24687222
TI  - Botulinum neurotoxin treatment for spasticity: the role of electromyography
      guidance.

PMID- 24687223
TI  - Haematological alterations induced by oral subacute exposure to fenvalerate,
      nitrate and their combination in domestic buffalo, Bubalus bubalis.
AB  - The present study investigated haematological alterations induced by oral
      subacute exposure to fenvalerate, nitrate and their combination in the domestic
      buffalo, Bubalus bubalis. Fenvalerate exposure produced significant declines in
      haemoglobin (Hb), total leukocyte count (TLC), total erythrocyte count (TEC) and
      mean corpuscular haemoglobin concentration (MCHC), and a corresponding elevation
      in mean corpuscular volume (MCV). Following oral exposure to sodium nitrate,
      significant declines in blood Hb, TLC, TEC, MCH and MCHC, and a significant
      elevation in MCV occurred. Combined exposure to fenvalerate and sodium nitrate
      produced severe effects with an appreciably more prominent decline in Hb, TLC,
      TEC and MCHC and a significant elevation in MCV. The percentage of methaemoglobin
      was observed to follow an elevating trend in animals exposed to sodium nitrate
      alone (0.69 %-13.8 %) and in combination with fenvalerate (0.75 %-13.7 %).

PMID- 24687224
TI  - Uptake and translocation of metals in different parts of crop plants irrigated
      with contaminated water from DEPZ area of Bangladesh.
AB  - Metal contamination in arable soils and crops grown in and around an industrial
      area of Bangladesh were measured, and the transfer factor from soils to crops was
      calculated accordingly. The highest concentration was observed for Fe and the
      order of metal concentration was Fe > Zn > Cr > Pb > Cu > Ni > Cd in soils.
      Bioaccumulation and translocation of metals from roots to edible parts of the
      crop plants were varied for almost all elements studied. Absorption of metals was
      significantly more in the roots compared to other plant parts. Accumulation of
      all metals in the edible parts of the plants was compared with the recommended
      maximum tolerable levels proposed by the Joint FAO/WHO Expert Committee on Food
      Additives. Bioconcentration factors values based on dry weights were below one
      for all metals except Cu in the rice roots and decreased in the order of Cu > Zn
      > Fe > Pb > Ni > Cd > Cr.

PMID- 24687225
TI  - Impact of a long term fire retardant (Fire Trol 931) on the leaching of Na, Al,
      Fe, Mn, Cu and Si from a Mediterranean forest soil: a short-term, lab-scale
      study.
AB  - Long term fire retardant (LTR) application for forest fire prevention purposes as
      well as wildland fires can result in chemical leaching from forest soils. Large
      quantities of sodium (Na), aluminium (Al), iron (Fe), manganese (Mn), copper (Cu)
      and silicon (Si) in leachates, mainly due to ammonium (one of the major LTR
      components) soil deposition, could affect the groundwater quality. The leaching
      of Na, Al, Fe, Mn, Cu and Si due to nitrogen based LTR application (Fire Trol
      931) was studied at laboratory scale. The concentrations of Na(+), Al(3+),
      Fe(3+)/Fe(2+), Mn(2+), Cu(2+) and Si(4+) were measured in the resulting leachates
      from pots with forest soil and pine trees alone and in combination with fire. The
      leaching of Na, Fe and Si from treated pots was significantly greater than that
      from control pots. The leaching of Al, Mn and Cu was extremely low.

PMID- 24687227
TI  - NHS should become a membership organisation, think tank says.

PMID- 24687226
TI  - Evaluation of the relationship between epicardial fat volume and left ventricular
      diastolic dysfunction.
AB  - PURPOSE: The aim of the present study was to evaluate the relationship between
      epicardial fat tissue (EFT) volume and left ventricular diastolic function.
      MATERIALS AND METHODS: A total of 63 patients (29 male, 34 female, mean age 57.8
      +/- 10.9 years) were enrolled in the study. Multidetector computed tomography
      (MDCT) and 2D transthoracic echocardiography were performed in 29 patients with
      left ventricular diastolic dysfunction and 34 patients with normal diastolic
      function. EFT volume and coronary calcium score were measured by MDCT. RESULTS:
      Mean EFT volume was 137.2 +/- 56.2 cm(3) for the whole study group. Mean EFT was
      114.1 +/- 46.6 cm(3) in patients with normal left ventricular diastolic function
      and 164.4 +/- 54.9 cm(3) in those with left ventricular diastolic dysfunction (p
      = 0.0002). Diastolic dysfunction had no significant correlation with diabetes,
      hypertension, and coronary calcium scoring (p > 0.05). Also in our patient group
      EFT volume had no significant correlation with coronary calcium score (r = 0.148,
      p = 0.248). CONCLUSION: Patients with left ventricular diastolic dysfunction had
      significantly increased EFT volume.

PMID- 24687228
TI  - Effects of SOD/catalase mimetic platinum nanoparticles on radiation-induced
      apoptosis in human lymphoma U937 cells.
AB  - Since polyacrylic acid capped platinum nano-particles (nano-Pts) are known to
      have a unique ability to quench superoxide (O2(-)) and hydrogen peroxide (H2O2),
      the anti-oxidant activity of nano-Pts against apoptosis induced by x-irradiation
      in human lymphoma U937 cells was investigated. DNA fragmentation assay, Annexin V
      FITC/PI by flow cytometry and Giemsa staining revealed a significant decrease in
      apoptosis induced by 10 Gy, when cells were pre-treated with nano-Pts in a dose
      dependent manner. Pre-treatment with nano-Pts significantly decreased radiation
      induced reactive oxygen species (ROS) production, Fas expression and loss of
      mitochondrial membrane potential as determined by flow-cytometry. Furthermore,
      western blot analysis also showed that the expression of cleaved caspase-3, Bid
      and cytosolic cytochrome-c were significantly reduced in nano-Pts pretreated
      cells. Due to the catalase mimetic activity of nano-Pts, these results indicate
      that pre-treatment of U937 cells with nano-Pts significantly protect radiation
      induced apoptosis by inhibiting intracellular ROS (mainly H2O2), which plays a
      key role in the induction of apoptosis, because of no practical observation of
      intracellular O2(-) formation.

PMID- 24687229
TI  - An evaluation of reading comprehension of expository text in adults with
      traumatic brain injury.
AB  - PURPOSE: This project was conducted to obtain information about reading problems
      of adults with traumatic brain injury (TBI) with mild-to-moderate cognitive
      impairments and to investigate how these readers respond to reading comprehension
      strategy prompts integrated into digital versions of text. METHOD: Participants
      from 2 groups, adults with TBI (n = 15) and matched controls (n = 15), read 4
      different 500-word expository science passages linked to either a strategy prompt
      condition or a no-strategy prompt condition. The participants' reading
      comprehension was evaluated using sentence verification and free recall tasks.
      RESULTS: The TBI and control groups exhibited significant differences on 2 of the
      5 reading comprehension measures: paraphrase statements on a sentence
      verification task and communication units on a free recall task. Unexpected group
      differences were noted on the participants' prerequisite reading skills. For the
      within-group comparison, participants showed significantly higher reading
      comprehension scores on 2 free recall measures: words per communication unit and
      type-token ratio. There were no significant interactions. CONCLUSION: The results
      help to elucidate the nature of reading comprehension in adults with TBI with
      mild-to-moderate cognitive impairments and endorse further evaluation of reading
      comprehension strategies as a potential intervention option for these
      individuals. Future research is needed to better understand how individual
      differences influence a person's reading and response to intervention.

PMID- 24687230
TI  - Growth and survival of pacific coho salmon smolts exposed as juveniles to
      pesticides within urban streams in western Washington, USA.
AB  - Pesticides are frequently detected in urban streams, with concentrations often
      exceeding those reported in surface waters within agricultural areas. The authors
      studied growth, survival, and return rates of coho salmon (Oncorhynchus kisutch)
      smolts exposed to a pesticide mixture ("cocktail") representative of the
      pesticides most frequently reported within urban streams in western Washington
      State, USA, in fall through early spring. Exposure concentrations were selected
      to represent a reasonable worst-case scenario based on field monitoring data.
      Smolts were continuously exposed to pulses of the cocktail either from
      fertilization through swim-up (2007-2008) or from fertilization through
      smoltification (2007-2008 and 2008-2009), coded wire tagged, and released in 2008
      and 2009. Pre-release endpoints (growth, survival, sex ratio, brain
      acetylcholinesterase activity, and gonado- and hepatosomatic indices) were not
      affected. However, the number of returning adults exposed to the cocktail to swim
      up (0.90%, n = 42) was more than double that of unexposed controls (0.38%, n =
      26) in 2008, whereas in 2009, fish exposed through smoltification returned in
      lower numbers (0.15%, n = 18) than controls (0.37%, n = 30). Variability in
      return rates among treatments between years was comparable to that observed in
      previous whole life cycle studies with Pacific salmon and other contaminants.
      Results suggest that exposure to pesticides in urban streams does not directly
      impair early life stages of coho salmon, and that additional studies
      incorporating releases of larger numbers of smolts across several years are
      necessary to adequately quantify effects on return rates.

PMID- 24687233
TI  - How FABulous is PEGgy? Certoliziumab pegol from the bench to the patients.

PMID- 24687234
TI  - Tumour necrosis factor alpha antagonists in the treatment of rheumatoid
      arthritis: an immunological perspective.
AB  - Rheumatoid arthritis (RA) is one of the most prevalent autoimmune conditions,
      affecting approximately 1% of the adult population. It is associated with
      decreased quality of life and considerable morbidity and mortality. Various
      inflammatory cells, including macrophages, neutrophils, mast cells, natural
      killer cells, B and T cells and stromal cells play key pathophysiological roles
      in joint inflammation and RA progression. Several cytokines, including
      interleukin (IL)-1alpha and/or IL-1beta, and tumour necrosis factor (TNF)-alpha,
      are involved at each stage of RA pathogenesis; namely, by augmenting
      autoimmunity, sustaining long-term inflammatory synovitis and promoting joint
      damage. Different cell types are involved in RA pathogenesis through upregulation
      of several cytokine and soluble pro-inflammatory mediators. As early as the late
      1980s, TNF had been identified as a potential target in RA. Five anti-TNF drugs,
      infliximab, adalimumab, certolizumab pegol, etanercept and golimumab, are now
      approved for the treatment of RA in various countries. All are bivalent
      monoclonal antibodies, with the exception of the monovalent certolizumab and
      etanercept, which is an engineered dimeric receptor. Although all react with and
      neutralise soluble TNF in vitro, structural differences in the molecules may
      contribute to differences in their therapeutic effects and the occurrence of side
      effects. Pegylated certolizumab permits once-monthly dosing. Other mechanisms of
      action proposed to be important for the efficacy of anti-TNF agents are as
      follows: induction of apoptosis of both monocytes and T cells; neutralization of
      membrane TNF; antibody-dependent cell-mediated and complement-dependent
      cytotoxicity; and reverse signaling via membrane TNF.

PMID- 24687236
TI  - Efficacy and safety of certolizumab pegol in rheumatoid arthritis: meeting
      rheumatologists' requirements in routine clinical practice.
AB  - Certolizumab pegol, a pegylated Fab' anti-tumour necrosis factor (TNF)-alpha
      agent, has shown efficacy in patients with rheumatoid arthritis (RA) unresponsive
      to previous treatment. In key randomised controlled trials involving patients
      with moderate to severe RA and an inadequate response to methotrexate or one or
      more disease-modifying antirheumatic drug (DMARD), the efficacy of certolizumab
      pegol, as monotherapy or with methotrexate, was similar to that reported in other
      anti-TNF clinical studies, with 60% or fewer of patients achieving American
      College of Rheumatology 20% improvement in RA. Rapid clinical response was also
      seen, with significant differences evident at week 1, and efficacy maintained at
      study end and in open-label extensions. Adding certolizumab pegol to non
      biological DMARDs is efficacious in other RA populations. In the CERTAIN study,
      certolizumab increased remission rates, prevented disease worsening and improved
      work productivity and daily activity in patients with low to moderate RA. In the
      REALISTIC study, rapid and consistent clinical responses were observed in a
      diverse group of anti-TNF-eligible RA patients representing those seen in
      clinical practice. In the RAPID studies, rapid and sustained reduction in RA
      signs and symptoms, inhibition of structural joint damage progression, and
      improved physical function were seen with certolizumab pegol plus methotrexate
      versus methotrexate alone in RA patients with an incomplete response to
      methotrexate. Certolizumab pegol was generally well-tolerated in clinical trials,
      although long-term observational data are not yet available. Current data suggest
      that certolizumab pegol suits a 'treat to target' approach, providing rapid and
      sustained improvements in RA signs and symptoms, and beneficial effects on
      workplace and home productivity in patients with RA.

PMID- 24687235
TI  - Pegylation of biological molecules and potential benefits: pharmacological
      properties of certolizumab pegol.
AB  - PEGylation of biological proteins, defined as the covalent conjugation of
      proteins with polyethylene glycol (PEG), leads to a number of biopharmaceutical
      improvements, including increased half-life, increased solubility and reduced
      aggregation, and reduced immunogenicity. Since their introduction in 1990,
      PEGylated proteins have significantly improved the management of various chronic
      diseases, including rheumatoid arthritis (RA) and Crohn's disease. Certolizumab
      pegol is the only PEGylated anti-tumour necrosis factor (TNF)-alpha agent. It is
      a PEGylated, humanised, antigen-binding fragment of an anti-TNF monoclonal
      antibody. Unlike other anti-TNF agents, it has no crystallisable fragment (Fc)
      domain. Because of its novel structure, certolizumab pegol may have a different
      mechanism of action to the other anti-TNF agents, and also has different
      pharmacodynamic properties, which could possibly translate to a different safety
      profile. Pharmacodynamic studies have shown that certolizumab pegol binds to TNF
      with a higher affinity than adalimumab and infliximab. Certolizumab pegol is also
      more potent at neutralising soluble TNF-mediated signalling than adalimumab and
      infliximab, and has similar or lesser potency to etanercept. Certolizumab pegol
      does not cause detrimental in vitro effects such as degranulation, loss of cell
      integrity, apoptosis, complement-dependent cytotoxicity and antibody-dependent
      cell-mediated cytotoxicity. Certolizumab pegol may also penetrate more
      effectively into inflamed arthritic tissue than other anti-TNF agents, and is not
      actively transported across the placenta during pregnancy. Pharmacokinetic
      studies in healthy volunteers demonstrated that single intravenous and
      subcutaneous doses of certolizumab pegol had predictable pharmacokinetics. The
      pharmacokinetics of certolizumab pegol in patients with RA and Crohn's disease
      were consistent with pharmacokinetics in healthy volunteers. 

PMID- 24687237
TI  - Application of a commercial immunoblot to define EBV IgG seroprofiles.
AB  - BACKGROUND: Immunoblot (IB) techniques using different Epstein-Barr virus (EBV)
      antigens have been applied for detecting specific antibodies, making possible to
      obtain EBV seroprofiles in a single determination. The aim of this study was to
      evaluate a commercial IB for the detection of EBV-specific IgG (Euroimmun,
      Lubeck, Germany). METHODS: A total of 117 samples classified as EBV primary
      recent infections (n = 70), past infections (n = 29), or not infected (n = 18)
      have been used. The samples were characterized by immunofluorescence, by testing
      EBV capsid antigens IgM and IgG (using indirect approaches) and EBV nuclear
      antigen (by anticomplement technique; Meridian Bioscience Inc.). RESULTS: Using
      the cut-off value as defined by the IB manufacturer, the concordance, relative
      sensitivity, and relative specificity were 85.5 (100/117), 94.3% (66/70), and
      72.3% (34/47), respectively. If a corrected cut-off value was considered to
      classify the samples, the corresponding corrected figures were 89.7, 88.6, and
      91.5%, respectively. CONCLUSION: Being a useful serological diagnostic tool, IB
      for testing EBV IgG seems to be an adequate approach to define EBV seroprofiles.
      However, efforts to better define the cut-off value should be made in order to
      improve the performance of the assay in evaluation.

PMID- 24687238
TI  - Reversible, photoinduced activation of P4 by low-coordinate main group compounds.
AB  - Two unique systems based on low-coordinate main group elements that activate P4
      are shown to quantitatively release the phosphorus cage upon short exposure to UV
      light. This reactivity marks the first reversible reactivity of P4, and the
      germanium system can be cycled 5 times without appreciable loss in activity.
      Theoretical calculations reveal that the LUMO is antibonding with respect to the
      main group element-phosphorus bonds and bonding with respect to reforming the P4
      tetrahedron, providing a rationale for this unprecedented activity, and
      suggesting that the process is tunable based on the substituents.

PMID- 24687239
TI  - Hip protectors for preventing hip fractures in older people.
AB  - BACKGROUND: Older people living in nursing care facilities or older adults living
      at home are at high risk of falling and a hip fracture may occur after a fall.
      Hip protectors have been advocated as a means to reduce the risk of hip fracture.
      Hip protectors are plastic shields (hard) or foam pads (soft), usually fitted in
      pockets in specially designed underwear.This is an update of a Cochrane review
      first published in 1999, and updated several times, most recently in 2010.
      OBJECTIVES: To determine if the provision of external hip protectors (sometimes
      referred to as hip pads or hip protector pads) reduces the risk of fracturing the
      hip in older people. SEARCH METHODS: We searched the Cochrane Bone, Joint and
      Muscle Trauma Group Specialised Register (December 2012), the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12),
      MEDLINE (1950 to week 3 November 2012), MEDLINE In-Process (18 December 2012),
      EMBASE (1988 to 2012 Week 50), CINAHL (1982 to December 2012), BioMed Central
      (January 2010), trial registers and reference lists of relevant articles.
      SELECTION CRITERIA: All randomised or quasi-randomised controlled trials
      comparing an intervention group provided with hip protectors with a control group
      not provided with hip protectors. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed risk of bias and extracted data. We sought
      additional information from trialists. Data were pooled using fixed-effect or
      random-effects models as appropriate. MAIN RESULTS: This review includes 19
      studies, nine of which were cluster randomised. These included approximately
      17,000 people (mean age range 78 to 86 years). Most studies were overall at low
      risk of bias for fracture outcomes. Trials tested hard or soft hip protectors
      enclosed in special underwear in 18 studies.Pooling of data from 14 studies
      (11,808 participants) conducted in nursing or residential care settings found
      moderate quality evidence for a small reduction in hip fracture risk (risk ratio
      (RR) 0.82, 95% confidence interval (CI) 0.67 to 1.00); the absolute effect is 11
      fewer people (95% CI, from 20 fewer to 0) per 1000 having a hip fracture when
      provided with hip protectors.There is moderate quality evidence when pooling data
      from five trials in the community (5614 participants) that shows little or no
      effect in hip fracture risk (RR 1.15, 95% CI 0.84 to 1.58); the absolute effect
      is two more people (95% CI 2 fewer to 6 more) per 1000 people having a hip
      fracture when provided with hip protectors.There is probably little to no effect
      on falls (rate ratio 1.02, 95% CI 0.9 to 1.16) or fractures other than of the hip
      or pelvis (rate ratio 0.87, 95% CI 0.71 to 1.07). However, the risk ratio for
      pelvic fractures is RR 1.27 (95% CI 0.78 to 2.08); this is an absolute effect of
      one more person (95% CI 1 fewer to 5 more) per 1000 having a pelvic fracture when
      provided with hip protectors.The incidence of adverse events while wearing hip
      protectors, including skin irritation, ranged from 0% to 5%. Adherence,
      particularly in the long term, was poor. AUTHORS' CONCLUSIONS: Hip protectors
      probably reduce the risk of hip fractures if made available to older people in
      nursing care or residential care settings, without increasing the frequency of
      falls. However, hip protectors may slightly increase the small risk of pelvic
      fractures. Poor acceptance and adherence by older people offered hip protectors
      is a barrier to their use. Better understanding is needed of the personal and
      design factors that may influence acceptance and adherence.

PMID- 24687240
TI  - EHR in emergency rooms: exploring the effect of key information components on
      main complaints.
AB  - This study characterizes the information components associated with improved
      medical decision-making in the emergency room (ER). We looked at doctors'
      decisions to use or not to use information available to them on an electronic
      health record (EHR) and a Health Information Exchange (HIE) network, and tested
      for associations between their decision and parameters related to healthcare
      outcomes and processes. Using information components from the EHR and HIE was
      significantly related to improved quality of healthcare processes. Specifically,
      it was associated with both a reduction in potentially avoidable admissions as
      well as a reduction in rapid readmissions. Overall, the three information
      components; namely, previous encounters, imaging, and lab results emerged as
      having the strongest relationship with physicians' decisions to admit or
      discharge. Certain information components, however, presented an association
      between the diagnosis and the admission decisions (blood pressure was the most
      strongly associated parameter in cases of chest pain complaints and a previous
      surgical record for abdominal pain). These findings show that the ability to
      access patients' medical history and their long term health conditions (via the
      EHR), including information about medications, diagnoses, recent procedures and
      laboratory tests is critical to forming an appropriate plan of care and
      eventually making more accurate admission decisions. 

PMID- 24687241
TI  - Nanocarrier for poorly water-soluble anticancer drugs--barriers of translation
      and solutions.
AB  - Many existing chemotherapeutic drugs, repurposed drugs and newly developed small
      molecule anticancer compounds have high lipophilicity and low water-solubility.
      Currently, these poorly water-soluble anticancer drugs (PWSAD) are generally
      solubilized using high concentrations of surfactants and co-solvents, which
      frequently lead to adverse side effects. In recent years, researchers have been
      actively exploring the use of nanotechnology as an alternative to the solvent
      based drug solubilization approach. Several classes of nanocarrier systems (lipid
      based, polymer-based and albumin-based) are widely studied for encapsulation and
      delivery of the existing and new PWSAD. These nanocarriers were also shown to
      offer several additional advantages such as enhanced tumour accumulation, reduced
      systemic toxicity and improved therapeutic effectiveness. In this article, the
      recent nanotechnological advances in PWSAD delivery will be reviewed. The
      barriers commonly encountered in the development of PWSAD nanoformulations (e.g.
      formulation issues and nanotoxicity issues) and the strategies to overcome these
      barriers will also be discussed. It is our goal to provide the pharmaceutical
      scientists and clinicians with more in-depth information about the nanodelivery
      approach, thus, more efficacious and safe PWSAD nanoformulations can be developed
      with improved translational success. 

PMID- 24687242
TI  - Particle margination and its implications on intravenous anticancer drug
      delivery.
AB  - "Margination" refers to the movement of particles in flow toward the walls of a
      channel. The term was first coined in physiology for describing the behavior of
      white blood cells (WBCs) and platelets in blood flow. The margination of
      particles is desirable for anticancer drug delivery because it results in the
      close proximity of drug-carrying particles to the endothelium, where they can
      easily diffuse into cancerous tumors through the leaky vasculature. Understanding
      the fundamentals of margination may further lead to the rational design of
      particles and allow for more specific delivery of anticancer drugs into tumors,
      thereby increasing patient comfort during cancer treatment. This paper reviews
      existing theoretical and experimental studies that focus on understanding
      margination. Margination is a complex phenomenon that depends on the interplay
      between inertial, hydrodynamic, electrostatic, lift, van der Waals, and Brownian
      forces. Parameters that have been explored thus far include the particle size,
      shape, density, stiffness, shear rate, and the concentration and aggregation
      state of red blood cells (RBCs). Many studies suggested that there exists an
      optimal particle size for margination to occur, and that nonspherical particles
      tend to marginate better than spherical particles. There are, however,
      conflicting views on the effects of particle density, stiffness, shear rate, and
      RBCs. The limitations of using the adhesion of particles to the channel walls in
      order to quantify margination propensity are explained, and some outstanding
      questions for future research are highlighted.

PMID- 24687243
TI  - Evaluation of implementation, compliance and acceptance of partial smoking bans
      among hospitality workers before and after the Swiss Tobacco Control Act.
AB  - BACKGROUND: The World Health Organization recommends uniform comprehensive
      smoking bans in public places. In Switzerland, regulations differ between various
      areas and are mostly incomplete for hospitality venues. As ambiguous regulations
      offer more leeway for implementation, we evaluated the Swiss regulations with
      respect to their effects on implementation, acceptance and compliance among
      hospitality workers. METHODS: In our longitudinal study, a standardized, self
      administered questionnaire was mailed to a sample of 185 hospitality workers
      before and 4-6 month after the smoking ban came into effect. The matched
      longitudinal sample comprised 71 participants (repeated response rate 38.4%). We
      developed a seven-item acceptance scale. Logistic regressions were performed to
      explore the factors associated with acceptance. RESULTS: Acceptance of smoking
      bans was influenced by smoking status and perceived annoyance with second-hand
      smoke in private. Although not statistically significant (P = 0.09), we found
      some indications that post-ban acceptance increased in an area with strict
      regulations, whereas it decreased in two areas with less stringent regulations.
      CONCLUSIONS: Tobacco bans in Swiss hospitality venues are still in a period of
      consolidation. The incomplete nature of the law may also have had a negative
      impact on the development of greater acceptance.

PMID- 24687244
TI  - Clinical applications of 3D T2-weighted MRI in pelvic imaging.
AB  - OBJECTIVE: The purpose of this article is to illustrate clinical applications of
      3D T2-weighted MRI in pelvic imaging. We review technical considerations of 3D T2
      weighted MRI with clinical examples. CONCLUSION: 3D T2-weighted MRI has been
      increasingly utilized for pelvic applications, including imaging of rectal
      cancer, prostate cancer, anorectal fistulas and the female pelvis. This
      relatively rapid technique offers good soft-tissue contrast of the pelvic organs,
      with potential for more widespread clinical use.

PMID- 24687245
TI  - Nonenhanced renal MR angiography using steady-state free precession (SSFP) and
      time-spatial labeling inversion pulse (Time-SLIP): repeatability and comparison
      of different tagging location.
AB  - PURPOSE: To prospectively determine the repeatability of noncontrast-enhanced
      renal arterial angiography with steady-state free precession (SSFP) and time
      spatial labeling inversion pulse (Time-SLIP), and to compare the visibility of
      renal artery and its branches when different locations of tagging pulse were
      placed. METHODS: Thirty-six young healthy volunteers were enrolled in this study
      and were twice examined by noncontrast-enhanced renal arterial angiography with
      SSFP and Time-SLIP in 1.5T MR scanner. Measurement error and repeatability were
      assessed for each of the five major parameters [vessel-to-kidney ratio (VKR),
      grade of renal arterial branching, grading of image quality, diameter and area of
      the main renal artery] using the Bland-Altman plot. Two independent observers
      recorded the values of the parameters; Inter- and intra-observer agreement was
      assessed using the intraclass correlation coefficients (ICCs). The same
      parameters, acquired at the tagging pulse placed just above the superior poles of
      both kidneys or closer to the main renal arteries, were compared using the
      Wilcoxon signed-rank test. RESULTS: Grading of arterial branching by the Time
      SLIP SSFP was satisfactorily reproducible with the mean score of greater 3.83
      indicating the visibility of branches within the renal parenchyma. The image
      quality was excellent for Segment I (the main trunk of renal artery) and good for
      Segment II (segmental branches pre renal parenchyma) and III (vessels within the
      renal parenchyma) with a satisfying repeatability between two examinations and a
      good inter- and intra-observer agreement. The ICCs for the inter- and intra
      observer measurements of both diameter and area of the main arteries ranged from
      0.781 to 0.934, indicating very good agreement. The repeatability of VKR was poor
      between the two examinations and at the two different tagging pulse locations.
      The position of tagging pulse in the origination of the main renal arteries was
      better than in the superior poles of kidneys as it provided a better
      visualization of arterial branches. CONCLUSION: Noncontrast-enhanced renal artery
      angiography with SSFP and Time-SLIP yields reliable and reproducible
      visualization of normal renal arteries. Localization of the tagging pulse closer
      to the main renal arteries provides better visibility of renal artery and its
      branches than the tag placement just above the superior poles of both kidneys.

PMID- 24687246
TI  - Molecular materials for organic photovoltaics: small is beautiful.
AB  - An overview of some recent developments of the chemistry of molecular donor
      materials for organic photovoltaics (OPV) is presented. Although molecular
      materials have been used for the fabrication of OPV cells from the very beginning
      of the field, the design of molecular donors specifically designed for OPV is a
      relatively recent research area. In the past few years, molecular donors have
      been used in both vacuum-deposited and solution-processed OPV cells and both
      fields have witnessed impressive progress with power conversion efficiencies
      crossing the symbolic limit of 10 %. However, this progress has been achieved at
      the price of an increasing complexity of the chemistry of active materials and of
      the technology of device fabrication. This evolution probably inherent to the
      progress of research is difficult to reconcile with the necessity for OPV to
      demonstrate a decisive economic advantage over existing silicon technology. In
      this short review various classes of molecular donors are discussed with the aim
      of defining possible basic molecular structures that can combine structural
      simplicity, low molecular weight, synthetic accessibility, scalability and that
      can represent possible starting points for the development of simple and cost
      effective OPV materials. 

PMID- 24687247
TI  - In situ antimicrobial activity on oral biofilm: essential oils vs. 0.2 %
      chlorhexidine.
AB  - OBJECTIVES: This study aims to evaluate the in situ antibacterial activity of a
      mouthwash containing essential oils (M-EO) on undisturbed de novo plaque-like
      biofilm (PL-biofilm) up to 7 h after its application. PATIENTS AND METHODS: An
      appliance was designed to hold six glass disks on the buccal sides of the lower
      teeth, allowing PL-biofilm growth. Fifteen healthy volunteers wore the appliance
      for 48 h and then performed a M-EO. Disks were removed after 30 s and at 1, 3, 5,
      and 7 h later. After a washout period, the same procedure was repeated with a M
      WATER and a M-0.2 % chlorhexidine. After PL-biofilm vital staining, samples were
      analyzed using a confocal laser scanning microscope. RESULTS: At 30 s after M-EO,
      the levels of bacterial vitality were 1.18 %, significantly lower than that of
      the basal sample (p < 0.001). After 7 h, the antibacterial effect of essential
      oils was still patent with a 47.86 % difference in bacterial vitality compared to
      the basal sample (p < 0.001). CONCLUSION: A single M-EO presents high
      antibacterial immediate activity and penetration capacity in situ and a
      substantivity which lasts for at least 7 h after its application over de novo
      biofilm. These results were better than those observed with 0.2 % chlorhexidine
      under the same conditions. CLINICAL RELEVANCE: A single M-EO is an effective
      measure against the de novo biofilm, presenting a good alternative to
      clorhexidine such as a preoperative rinse, in periodontal procedures or post
      treatment applications.

PMID- 24687248
TI  - Comparison of Forsus FRD EZ and Andresen activator in the treatment of class II,
      division 1 malocclusions.
AB  - OBJECTIVES: Purpose of this study is to evaluate the effects of Forsus Fatigue
      Resistant Device (FRD) EZ and Andresen activator in terms of skeletal, dental,
      and soft tissue changes in actively growing patients presenting with class II,
      division 1 malocclusion. MATERIALS AND METHODS: Study sample included 60
      subjects. Inclusion criteria were as follows: class II division 1 malocclusion,
      retrognathic mandible, normal or low-angle growth pattern, and peak growth
      period. The first study group consisted of 20 patients who were treated with
      Forsus appliance, and the second group of 20 patients received treatment with
      Andresen activator. Control group received no treatment. RESULTS: Our results
      revealed that both appliances enhanced mandibular growth, helped increase the
      length of the mandible, and had a restraining growth effect on the maxilla.
      Anterior face height increased in both of treatment groups, whereas posterior
      face height had a significant increase in the activator group only. More
      mandibular incisors protrusion and intrusion were seen with the Forsus appliance.
      Moreover, occlusal plane and palatal plane rotated significantly in clockwise
      direction as a result of dentoalveolar changes only in the Forsus group.
      CONCLUSIONS: As well as the Forsus appliances corrected class II discrepancies
      mostly through dentoalveolar changes as compared to the activator group, both
      appliances proved effective in the treatment of growing individuals having class
      II malocclusions with mandibular retrognathia. CLINICAL RELEVANCE: By this
      investigation, two treatment methods, which are currently used in clinical
      practice, will be evaluated, and the results will be useful for clinicians.

PMID- 24687249
TI  - Five-year evaluation of a low-shrinkage Silorane resin composite material: a
      randomized clinical trial.
AB  - OBJECTIVES: The aim of the present study was to investigate the clinical
      performance of a low-shrinkage silorane-based composite material (FiltekTM
      Silorane, 3 M-Espe) by comparing it with a methacrylate-based composite material
      (Ceram*XTM, Dentsply DeTrey). MATERIAL AND METHODS: A number of 72 patients (158
      restorations) participated in the study. After 5 years, a total of 107
      restorations (52 FiltekTM Silorane, 55 Ceram*XTM) in 48 patients were evaluated.
      Only class II restorations were included. All the restorations were placed by the
      same dentist, and the restorations were scored by one experienced
      dentist/evaluator. Materials were applied following the manufacturer's
      instructions. The primary outcome was marginal adaptation. Secondary outcomes
      were: marginal discoloration, approximal contact, anatomic form, fracture,
      secondary caries, and hypersensitivity. RESULTS: After 5 years, no statistically
      significant differences between the two materials were found in marginal
      adaptation either occlusally (p = 0.96) or approximally (p = 0.62). No
      statistically significant differences were found between the two materials in
      terms of approximal contact, anatomic form, fractures, or discoloration.
      Secondary caries was found in two teeth (FiltekTM Silorane). One tooth showed
      hypersensitivity (Ceram*XTM). CONCLUSION: Restorations of both materials were
      clinically acceptable after 5 years. This study did not find any advantage of the
      silorane-based composite over the methacrylate-based composite, which indicates
      that the low-shrinkage of FiltekTM Silorane may not be a determinant factor for
      clinical success in class II cavities. CLINICAL RELEVANCE: This paper is the
      first to evaluate the 5-year clinical performance of a low-shrinkage composite
      material.

PMID- 24687250
TI  - Quantitative study of cellular heterogeneity in doxorubicin uptake and its
      pharmacological effect on cancer cells.
AB  - Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with
      pharmacological effect on cancer cells were quantitatively investigated for the
      first time. An in vitro experimental model was established by treating human
      leukemia K562 and breast cancer MCF-7 cells with different schedules of DOX with
      or without surface P-glycoprotein (P-gp) inhibitor verapamil (VER). The cellular
      heterogeneity in DOX uptake was quantitatively examined by single-cell analysis
      using capillary electrophoresis coupled with laser-induced fluorescence
      detection. The corresponding cytotoxic effect was tested by cellular morphology,
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium and flow cytometry assays.
      The expression of cellular membrane surface P-gp was determined by flow
      cytometry. Results showed that the cellular heterogeneity exists in DOX uptake.
      The single-high DOX schedule leads to lower uptake heterogeneity and higher mean
      drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively
      correlated with drug cytotoxicity and surface P-gp expression, with r = -0.7680
      to ~ -0.9587. VER reduces the cellular variation in DOX uptake, suggesting that
      surface P-gp may be one of the causes of the cellular heterogeneity in DOX
      uptake. This research demonstrates the importance of quantitative study of
      cellular heterogeneity in drug uptake and its potential application in drug
      schedule design, response prediction and therapy modulation.

PMID- 24687251
TI  - The efficacy of nebulized salbutamol, magnesium sulfate, and salbutamol/magnesium
      sulfate combination in moderate bronchiolitis.
AB  - The aim of this paper is to compare the effect of nebulized magnesium sulfate to
      nebulized salbutamol and salbutamol/magnesium sulfate on successful discharge
      from the emergency department. A total of 56 infants were included in this double
      blinded, prospective study. Infants were grouped according to the nebulized
      treatment they received: group 1-salbutamol/normal saline, group 2-magnesium
      sulfate and normal saline, and group 3-salbutamol plus magnesium sulfate. Heart
      beat, bronchiolitis, clinical severity scores (CSS), and oxygen saturation of the
      patients were determined before and after nebulization (0, 1, 4 h). The patients
      were monitored for adverse reactions. Post-treatment mean CSS results were
      significantly lower than pre-treatment scores in all groups at 4 h with no
      significant difference within groups. CSS scores were lower in the
      salbutamol/magnesium sulfate group when compared with the magnesium sulfate and
      salbutamol groups (3.4 (2.4-4.3), 4.7 (3.8-5.7), 4.0 (3.2-4.3)). CSS were
      significantly lower than those from the magnesium sulfate group. CONCLUSION:
      Nebulized magnesium sulfate plus salbutamol may have additive effects for
      improving the short-term CSS.

PMID- 24687252
TI  - [Chronic ankle joint instability: in unrecognized distal rupture of the
      syndosmosis and malunion of the distal fibula].
AB  - BACKGROUND: It is often difficult in the acute phase to diagnose a lesion of the
      distal tibiofibular syndesmosis. If this lesion is overlooked, the patient will
      develop an incongruity of the upper ankle joint with a pathological external
      rotation of the talus. The risk of a possible premature arthritis is clearly
      increased. OBJECTIVES: In this case study a distal rupture of the syndesmosis in
      a young patient was overlooked in the initial diagnostic work-up. METHODS: A
      search of the relevant literature and a case report. RESULTS: In the case
      described the shortened fibula and chronic instability of the tibiofibular
      syndesmosis were repaired with a lengthening and derotational osteotomy and
      reconstruction using the gracilis muscle tendon. Through this method an exact
      reconstruction of the normal anatomy could be achieved. CONCLUSION: Posttraumatic
      misalignment in the ankle joint is associated with a high risk of secondary
      degenerative lesions. In cases with suspicion of a syndesmosis lesion,
      confirmation of the diagnosis is imperative so as to perform an anatomic
      repositioning and reconstruction of stability.

PMID- 24687253
TI  - SSAT/ASCRS Joint Symposium: controversies in surgery for ulcerative colitis.
AB  - The following is a summary of Session 2: Inflammatory and Infectious Bowel
      Disease within the Maintenance of Certification (MOC) course directed by Jeffrey
      B. Matthews, MD, President of the Society of Surgery of the Alimentary Tract.
      This MOC course was held in Orlando, FL, USA on Saturday, May 18, 2013 during
      Digestive Diseases Week. Multiple disciplines, including gastroenterology, with
      general and colon and rectal surgery, were represented at the session. 

PMID- 24687254
TI  - Mid to distal small bowel resection with the preservation of the terminal ileum
      improves glucose homeostasis in diabetic rats by activating the hindgut-dependent
      mechanism.
AB  - BACKGROUND: The aim of this study was to develop a novel surgical model to test
      the "hindgut hypothesis" and thereby study the role of the gut in glucose
      homeostasis and the mechanism of action of bariatric surgery. METHOD: Sprague
      Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg
      streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid
      to distal small bowel resection with the preservation of the terminal ileum
      (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation
      only) groups. Rats were observed for 12 weeks after the operation. The main
      outcome measures were weight, food intake, non-fasting glucose, an oral glucose
      tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and
      glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum
      bile acids, and lipid profile. RESULT: The DBRPI and sham groups exhibited no
      difference in weight and food intake after surgery. When compared to the sham
      controls, the DBRPI group displayed an improvement in non-fasting glucose, oral
      glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI
      elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks
      postoperation; furthermore, DBRPI resulted in higher serum levels of
      triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and
      lower free fatty acid level at 12 weeks. CONCLUSIONS: This study provides strong
      evidences for the key role of hindgut in the amelioration of diabetes after
      bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and
      effective surgical model for testing the "hindgut hypothesis" and focused study
      of biliary enterohepatic recycling in the context of bariatric operations.

PMID- 24687255
TI  - Adenosine A2A receptor antagonists in Parkinson's disease: progress in clinical
      trials from the newly approved istradefylline to drugs in early development and
      those already discontinued.
AB  - Neurotransmitters other than dopamine, such as norepinephrine, 5
      hydroxytryptamine, glutamate, adenosine and acetylcholine, are involved in
      Parkinson's disease (PD) and contribute to its symptomatology. Thus, the progress
      of non-dopaminergic therapies for PD has attracted much interest in recent years.
      Among new classes of drugs, adenosine A2A antagonists have emerged as promising
      candidates. The development of new highly selective adenosine A2A receptor
      antagonists, and their encouraging anti-parkinsonian responses in animal models
      of PD, has provided a rationale for clinical trials to evaluate the therapeutic
      potential and the safety of these agents in patients with PD. To date, the
      clinical research regarding A2A antagonists and their potential utilization in PD
      therapy continues to evolve between drugs just or previously discontinued
      (preladenant and vipadenant), new derivatives in development (tozadenant, PBF
      509, ST1535, ST4206 and V81444) and the relatively old drug istradefylline, which
      has finally been licensed as an anti-parkinsonian drug in Japan. All these
      compounds have been shown to have a good safety profile and be well tolerated.
      Moreover, results from phase II and III trials also demonstrate that A2A
      antagonists are effective in reducing off-time, without worsening troublesome
      dyskinesia, and in increasing on-time with a mild increase of non-troublesome
      dyskinesia, in patients at an advanced stage of PD treated with L-DOPA. In
      addition, early findings suggest that A2A antagonists might also be efficacious
      as monotherapy in patients at an early stage of PD. This review summarizes
      pharmacological and clinical data available on istradefylline, tozadenant, PBF
      509, ST1535, ST4206, V81444, preladenant and vipadenant. 

PMID- 24687256
TI  - Ginsenoside compound K inhibits angiogenesis via regulation of sphingosine kinase
      1 in human umbilical vein endothelial cells.
AB  - Ginsenoside compound K (CK) is a metabolite of the protopanaxadiol-type saponins
      of Panax ginseng C.A. Meyer (Araliaceae), has long been used to treat against the
      development of cancer, inflammation, allergies, and diabetes. This study examined
      the anti-angiogenic properties of CK against sphingosine 1-phosphate (S1P)
      induced cell migration via regulation of sphingosine kinase 1 (SPHK1) in human
      umbilical vein endothelial cells (HUVEC). Studies on S1P-induced cell migration,
      expression of SPHK1 and MMPs and analysis of sphingolipid metabolites by LC-MS/MS
      were examined after the treatment of CK (2.5, 5, 10 MUg/mL) in HUVEC. S1P
      produced by SPHK1 is also involved in cell growth, migration, and protection of
      apoptosis; therefore, we sought to investigate whether ginsenosides are able to
      regulate SPHK1. For this purpose, we developed an inhibitory assay of SPHK1
      activity and an analytical method for detection of S1P and other sphingolipid
      metabolites in HUVEC. Ginsenoside CK inhibited 100 nM S1P-induced cell migrations
      in a dose-dependent manner. Among tested ginsenosides, CK exclusively inhibited
      S1P production, SPHK1 activity and SPHK1 expression in HUVEC, whereas expression
      of the pro-apoptotic sphingolipids, sphingosine and ceramide, was increased in
      response to CK. The major subspecies of the increased ceramide was C24:0
      ceramide. CK also disrupted the sphingolipid rheostat, which ultimately
      influences cell fate, and dose-dependently inhibited HUVEC migration by reducing
      expression of metalloproteinases (MMPs). Ginsenoside CK acts as a unique HUVEC
      migration inhibitor by regulating MMP expression, as well as the activity of
      SPHK1 and its related sphingolipid metabolites.

PMID- 24687257
TI  - Hyperglycemia and survival rate in Asian patients with acute coronary syndrome.
AB  - Current studies are debating on the association of higher admission blood glucose
      (BG) and increased mortality of acute coronary syndrome (ACS). This study
      evaluated association of mortality between admission BG and BG control in 222
      patients with ACS who received coronary intervention in the intensive care unit.
      This study observed medical records through electronic medical record
      retrospectively and evaluated all patients who were admitted for the first attack
      of ST-segment elevation MI (STEMI), non-STEMI, and unstable angina pectoris.
      Admission BG higher than 220 mg/dl was statistically significantly associated
      with lower survival in patients; the association was stronger than in patients
      with admission BG higher than 140 mg/dl to less than 220 mg/dl and patients with
      admission BG less than 140 mg/dl (Wilcoxon test, p = 0.002). Survival time after
      admission was also associated with the history of diabetes mellitus (DM).
      Patients with diabetes had significantly lower survival than those without
      diabetes (Wilcoxon test, p = 0.028). Survival after ACS was not consistent with
      each insulin intervention of on admission to 6, 24, and 48 h after admission.
      There is a statistically significant association between admission BG higher than
      220 mg/dl and low survival but each intervention of post admission BG levels were
      not consistently associated with the mortality. Additionally, history of DM is
      associated with lower survival in patients with ACS on admission.

PMID- 24687258
TI  - A new megastigmane glycoside from Akebia quinata.
AB  - A new megastigmane glycoside, 8S*,9R*-megastigman-3-one-4,6-diene-8,9-diol-9-O
      beta-D-glucopyranoside, named akequintoside D (1), as well as six known
      compounds, roseoside II (2), 3-O-caffeoylquinic acid (3), methyl-3-O
      caffeoylquinate (4), 3,4,5-trimethoxyphenyl-beta-D-glucopyranoside (5),
      cuneataside D (6), 3,4-dimethoxyphenyl-6-O-(alpha-L-rhamnopyranosyl)-beta-D
      glucopyranoside (7) were isolated from the stem of Akebia quinata. The structures
      of compounds (1-7) were identified based on 1D and 2D NMR, including (1)H-(1)H
      COSY, HSQC, HMBC and NOESY spectroscopic analyses. The inhibitory activity of
      these isolated compounds against interleukin-6 (IL-6) production in TNF-alpha
      stimulated MG-63 cells was also examined. 

PMID- 24687259
TI  - Evaluation of multimeric siRNA conjugates for efficient protamine-based delivery
      into breast cancer cells.
AB  - Despite the preferable properties of well-defined cationic peptides for small
      interfering RNA (siRNA) delivery, their application as siRNA carriers remains
      limited due to their poor binding affinity with short-chain RNAs. In this study,
      we investigated the feasibility of a novel strategy for circumventing this
      limitation, by assessing the utility of multimeric conjugates of siRNA for
      improving the binding affinity of siRNAs with cationic peptides and the extent of
      intracellular delivery. Protamine, a natural and arginine-rich peptide, was used
      to produce stably condensed polyelectrolyte complexes (PECs) with multimeric
      siRNAs (multi-siRNA) with a size of 120 nm while conventional siRNA/protamine
      particles are over 500 nm. The formulated multi-siRNA/protamine PECs showed
      greatly enhanced stability, intracellular uptake, and biocompatibility compared
      to conventional, monomeric (mono)-siRNA/protamine particles. With the addition of
      chloroquine, multi-siRNA/protamine PECs successfully inhibited target gene
      expression in MDA-MB-435 cells, a breast cancer cell line, even in the presence
      of serum protein. This study demonstrates that multi-siRNA conjugates greatly
      facilitate the formulation of nano-sized protamine-based carriers and
      significantly improve intracellular delivery in vitro compared to common siRNAs,
      and therefore may provide a platform for the design of peptide-based siRNA
      delivery systems for in vivo applications. 

PMID- 24687260
TI  - The Santa Clara Strength of Religious Faith Questionnaire (SCSORF): a validation
      study on Iranian Muslim patients undergoing dialysis.
AB  - The Santa Clara Strength of Religious Faith Questionnaire (SCSORF) is an often
      used and validated scale that is uncommonly utilized in culturally diverse
      populations. The purpose of this research investigation was to adapt the SCSORF
      for use among Iranian Muslim patients undergoing dialysis and to examine the
      reliability and validity of the scale among this population. A total of 428
      patients (228 females, 200 males, M age = 52.2 years, SD = 10) were selected from
      five dialysis center in Tehran and Qazvin, Iran. A comprehensive forward-backward
      translation system was used for cross-cultural translation. Patients completed a
      baseline questionnaire obtaining demographic and clinical information as well as
      the SCSORF, the Age Universal Religious Orientation Scale (AUROS), the religious
      life inventory (RLI), and the Duke University religion index (DUREL). 2 weeks
      later, patients were asked to complete the SCSORF once again. Reliability of the
      SCSORF was examined using internal consistency and test-rest reliability.
      Convergent validity and factor structure using exploratory factor analysis (EFA)
      and confirmatory factor analysis (CFA) were also examined. Cronbach's alpha for
      the single construct of the SCSORF was 0.89 with adequate test-retest reliability
      measured over a 2 week period. SCSORF scores were significantly correlated with
      AUROS, RLI and the DUREL. The EFA generated a single factor solution for the
      SCSORF while these results were confirmed by the CFA in an independent sample.
      Findings demonstrated that the SCSORF has favorable reliability, convergent
      validity, and divergent validity among Iranian Muslim patients undergoing
      dialysis and is recommended for use by clinicians (e.g., nephrologists) to
      measure strength of religious faith among patients. 

PMID- 24687261
TI  - True Believers? Religion, Physiology, and Perceived Body Weight in Texas.
AB  - This paper examines relationships between body weight, religion, and gender while
      controlling for relevant covariates and body mass index (BMI), a measure of
      physical/biological body type. Using data from the 2004 Survey of Texas Adults (n
      = 1,504), we present results of ordered logistic regression models which indicate
      that religious factors work distinctly for men and women when controlling for
      BMI. While church attendance is associated with lower odds of overweight
      perceptions among women, it is religious salience that is associated with lower
      odds of self-reported excess weight in men. Implications for research which
      associates religious and physiological factors are discussed. 

PMID- 24687262
TI  - Post-exposure passive immunisation for preventing measles.
AB  - BACKGROUND: Measles outbreaks continue to occur in countries with high
      vaccination coverage. Passive immunisation is generally considered to prevent
      measles in someone who is not immune and has been exposed to infection. Estimates
      of effectiveness have varied and no minimum effective dose has been determined.
      OBJECTIVES: To assess the effectiveness and safety of intramuscular injection or
      intravenous infusion of immunoglobulins (passive immunisation) for preventing
      measles when administered to exposed susceptible people before the onset of
      symptoms. SEARCH METHODS: We searched CENTRAL (2013, Issue 7), MEDLINE (1946 to
      July week 5, 2013), CINAHL (1981 to August 2013) and EMBASE (1974 to August
      2013). SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi
      RCTs and prospective, controlled (cohort) studies if: participants were
      susceptible and exposed to measles, polyclonal immunoglobulins derived from human
      sera or plasma were administered intramuscularly or intravenously as the only
      intervention in at least one group and the number of subsequent measles cases was
      measured. We excluded studies of other sources of immunoglobulins. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and critically
      appraised the included studies. We attempted to contact study authors for missing
      information. We described the results of studies not included in meta-analyses.
      MAIN RESULTS: We included one RCT, two quasi-RCTs and 10 cohort studies (3925
      participants). No studies were rated as low risk of bias for all criteria.
      Critical appraisal was constrained by a lack of information in most studies. The
      overall quality of the evidence was moderate.Seven studies (1432 participants)
      assessed cases of measles after immunoglobulin versus no treatment. Heterogeneity
      was explained by subgrouping according to the blood product used as an
      approximation of dose of immunoglobulin. When given within seven days of
      exposure, immunoglobulins were effective at preventing measles: gamma globulin
      (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.08 to 0.36), convalescent
      serum (RR 0.21, 95% CI 0.15 to 0.29 to RR 0.49, 95% CI 0.44 to 0.54) and adult
      serum (RR 0.52, 95% CI 0.45 to 0.59). The differences in the effectiveness of
      different blood products were supported by studies not included in the meta
      analysis and by two studies (702 participants) that found gamma globulin more
      effective than serum (RR 0.56, 95% CI 0.46 to 0.69).Based on three studies (893
      participants) immunoglobulin was effective at preventing death due to measles
      compared to no treatment (RR 0.24, 95% CI 0.13 to 0.44).Two studies included
      measles vaccine alone among the intervention groups. Meta-analysis could not be
      undertaken. Both studies suggested the vaccine was more effective than gamma
      globulin.No serious adverse events were observed in any of the included studies,
      although reporting of adverse events was poor overall. Non-serious adverse events
      included transient fever, rash, muscle stiffness, local redness and induration.
      AUTHORS' CONCLUSIONS: Passive immunisation within seven days of exposure is
      effective at preventing measles, with the risk for non-immune people up to 83%
      less than if no treatment is given. Given an attack rate of 45 per 1000 (per the
      control group of the most recent included study), gamma globulin compared to no
      treatment has an absolute risk reduction (ARR) of 37 per 1000 and a number needed
      to treat to benefit (NNTB) of 27. Given an attack rate of 759 per 1000 (per the
      attack rate of the other included study assessing gamma globulin), the ARR of
      gamma globulin compared to no treatment is 629 and the NNTB is two.It seems the
      dose of immunoglobulin administered impacts on effectiveness. A minimum effective
      dose of measles-specific antibodies could not be identified.Passive immunisation
      is effective at preventing deaths from measles, reducing the risk by 76% compared
      to no treatment. Whether the benefits of passive immunisation vary among
      subgroups of non-immune exposed people could not be determined.Due to a paucity
      of evidence comparing vaccine to passive immunisation, no firm conclusions can be
      drawn regarding relative effectiveness.The included studies were not specifically
      designed to detect adverse events.Future research should consider the
      effectiveness of passive immunisation for preventing measles in high-risk
      populations such as pregnant women, immunocompromised people and infants. Further
      efforts should be made to determine the minimum effective dose of measles
      specific antibodies for post-exposure prophylaxis and the relative effectiveness
      of vaccine compared to immunoglobulin.

PMID- 24687263
TI  - Product characteristics and quality of bovine blood-enriched dried vegetable
      paste.
AB  - BACKGROUND: The aim of this study was to evaluate a preparation of vegetable
      paste with bovine blood in order to maximize the protein content using linear
      programming, and to analyze the product characteristics and quality of bovine
      blood-enriched vegetable paste dried in a spouted bed. The drying experiments
      were performed by evaluating the effects of inlet air temperature, paste flow
      rate and paste solids concentration on the dried product characteristics and
      quality (functional and nutritional properties). RESULTS: The vegetable paste
      enriched with bovine blood was a good source of protein (~0.20 g g(-1) , dry
      basis), and the linear programming was adequate to select the constituents
      (carrot, onion, potato, kale, tomato, soybean oil and bovine blood) and optimize
      their quantities. The drying conditions of bovine blood-enriched vegetable paste
      in the spouted bed that gave the best product characteristics were an air
      temperature of 110  degrees C and a paste flow rate of 600 mL h(-1) with 0.07 g
      g(-1) solids concentration. CONCLUSION: The addition of bovine blood to vegetable
      paste by linear programming increased the protein content of the paste and
      improved its functional properties and digestibility. The powder obtained from
      the spouted bed drier showed suitable functional and nutritional properties and
      was also a good source of antioxidant compounds.

PMID- 24687264
TI  - Comments on "Injection lipolysis with phosphatidylcholine and deoxycholate".

PMID- 24687265
TI  - Harvest of superficial layers of fat with a microcannula and isolation of adipose
      tissue-derived stromal and vascular cells.
AB  - BACKGROUND: Adipose tissue is a source of stromal and vascular cells suitable for
      regenerative medical applications. Cell recovery depends on several factors,
      including the characteristics of the cannula used to harvest tissue. OBJECTIVES:
      The authors assess whether aspiration of superficial layers of adipose tissue
      performed with a microcannula, rather than a standard cannula, allows for
      improved isolation of stromal and vascular cells, and they evaluate the
      angiogenic potential of the isolated cells in vitro and in vivo. METHODS: Adipose
      derived stromal and stem cells (ADSC) were collected from the lipoaspirate of the
      abdomen and hip regions of 6 healthy female donors. For adipose tissue harvest,
      several options were compared: (1) a rounded-tip cannula with a length of 170 mm,
      a diameter of 3 mm, and a single elliptic suction port on the side near its
      distal end (port diameter: 3 * 9 mm) or (2) a rounded-tip infiltration cannula
      with a length of 170 mm, a diameter of 2 mm, and 5 round ports placed spirally
      along the sides of the distal cannula shaft (each port diameter: 1 mm) (Shipper
      Medical Technologies Corporation, Centennial, Colorado). Isolated cells were
      characterized for (1) expression of the endothelial specific marker CD31 by
      immunohistochemical and cytofluorimetric analyses and (2) tubular-like structure
      formation using a 3-dimensional angiogenesis assay on Matrigel. Human ADSC were
      transduced to express firefly luciferase as a marker suitable for bioluminescent
      tracking and transplantation studies into immunosuppressed mice were performed.
      RESULTS: ADSC yield was determined to be significantly higher in samples
      collected with the microcannula (P = .04). Moreover, isolated cells acquired
      typical endothelial-like morphology in vitro, formed capillary-like structures,
      and expressed the distinctive endothelial cell marker CD31. Cells implanted into
      immunosuppressed mice persisted for several weeks in areas undergoing
      neovascularization. CONCLUSIONS: These results suggest that aspiration of adipose
      tissue with a microcannula can be a minimally invasive method to obtain
      clinically relevant numbers of stromal and vascular cells useful for autologous
      transplant procedures and for promoting tissue regeneration and
      neovascularization.

PMID- 24687266
TI  - Phonological assessment and analysis of bilingual preschoolers' Spanish and
      English word productions.
AB  - PURPOSE: The major purpose of this study was to examine Spanish and English
      phonological productions (patterns/deviations) of typically developing bilingual
      preschool children. Phonological scores were compared in order to determine if
      significant differences exist between (a) boys and girls, (b) 4- and 5-year-olds,
      and/or (c) their productions of Spanish and English words. METHOD: Fifty-six
      bilingual 4- and 5-year-old children (27 boys and 29 girls) who attended Head
      Start programs named stimulus items for Spanish and English phonological
      assessment instruments that were similar in procedures and analyses. RESULTS:
      Multivariate analyses indicated no significant differences for phonological
      scores between boys and girls or between the 2 languages. Differences between the
      4- and 5-year-olds, however, were significant, with the 5-year-olds performing
      better than the 4-year-olds. Liquid deviations and omissions of consonants in
      clusters/sequences were the most frequently occurring phonological deviations.
      CONCLUSIONS: Phonological score differences between typically developing
      bilingual Spanish-English-speaking preschool boys and girls from similar
      backgrounds are not likely to be significant. Better phonological scores,
      however, can be expected for 5-year-olds than for 4-year-olds. Moreover,
      phonological deviation percentage scores of typically developing bilingual
      children for comparable Spanish and English assessment instruments are likely to
      be similar.

PMID- 24687267
TI  - The effect of femoro-acetabular impingement on the kinematics and kinetics of the
      hip joint.
AB  - Gait analysis is an objective tool that has been used to assess and monitor
      treatment for many musculoskeletal conditions. Recently, it has been used to
      assess the impact of femoro-acetabular impingement (FAI) on the hip and lower
      limb movements. There have been a fairly limited number of studies published so
      far reporting unexpected and inconsistent results, which calls for more research
      to be conducted in this arena. In the light of the limited data available, it has
      been challenging to reconcile the contradictions in some of these results, and
      therefore no coherent conclusions could be drawn. In this short article, we
      attempt to explain some of the abnormal kinematic and kinetic patterns associated
      with FAI by highlighting similarities between the gait seen in early
      osteoarthritis (OA) and that of FAI. We also propose an approach for future
      research in this field and emphasise the importance of quantifying early OA in
      FAI based on magnetic resonance imaging (MRI) scans and the amount of chondral
      damage seen during open or arthroscopic surgery. 

PMID- 24687268
TI  - The history of internal fixation of proximal femur fractures Ernst Pohl-the
      genius behind.
AB  - The most frequently used implants for internal fixation of proximal femoral
      fractures are currently the dynamic hip screw and the intramedullary hip nail.
      However, little has been written about one of the pioneers in this field, a
      German genius, the designer Ernst Pohl (1876-1962). Without his involvement the
      concepts of intramedullary nailing coined by Gerhard Kuntscher, Richard Maatz and
      other surgeons could hardly have been implemented. Through his achievements Pohl
      has rightly merited his pre-eminent position in the history of bone surgery. This
      article outlines the extraordinary contribution of Ernst Pohl to the development
      of skeletal surgery and radiology, as well as other medical disciplines. 

PMID- 24687269
TI  - A prospective study to assess the outcomes of revision anterior cruciate ligament
      reconstruction.
AB  - PURPOSE: Continuously increasing numbers of primary anterior cruciate ligament
      (ACL) reconstructions invites a parallel increase in graft failures and need for
      revision ACL reconstruction surgery. High failure rates has previously
      stigmatised the revision surgery. We performed this study using multiple outcome
      measures together with clinical examination to offer a full assessment of the
      outcomes of this procedure. METHODS: Twenty patients, with mean age of 29.4 years
      (17-50 years), were included in this study prior to their revision ACL
      reconstruction surgery. All patients were followed prospectively collecting the
      Knee injury and Osteoarthritis Outcome (KOOS), International Knee Documentation
      Committee (IKDC) and Tegner-Lysholm scores pre- and post-operatively together
      with clinical assessment of the antero-posterior knee laxity. RESULTS: After a
      mean follow up interval of 30 months (16-60 months) significant post-operative
      improvement of IKDC, Tegner-Lysholm scores and knee antero-posterior laxity
      together with the Symptoms, Activities of Daily Living (ADL) and Quality of Life
      (QOL) components of the KOOS score was noticed (P < 0.05). However, there was no
      similar improvement in pain and sports components of the KOOS score (P > 0.05).
      There was no difference in the outcomes of different graft types. CONCLUSION:
      Good outcomes of revision ACL reconstruction surgery are achievable. The use of
      different graft types did not affect the outcome of the procedure. Most of the
      patients opted to less aggressive sports participation after the revision
      procedure.

PMID- 24687271
TI  - Hypoiodite-mediated cyclopropanation of alkenes.
AB  - An efficient, transition metal-free procedure for the cyclopropanation of alkenes
      using malononitrile and the LiI-tBuOCl combination under mild reaction conditions
      is described. The reaction mechanism most likely involves tBuOI generated in situ
      from LiI and tBuOCl. The utility of this new methodology has been demonstrated by
      the synthesis of a potential HIV-1 RT inhibitor. 

PMID- 24687270
TI  - Examination of genetic variation in GABRA2 with conduct disorder and alcohol
      abuse and dependence in a longitudinal study.
AB  - Previous studies have shown associations between single nucleotide polymorphisms
      (SNPs) in gamma aminobutyric acid receptor alpha 2 (GABRA2) and adolescent
      conduct disorder (CD) and alcohol dependence in adulthood, but not adolescent
      alcohol dependence. The present study was intended as a replication and extension
      of this work, focusing on adolescent CD, adolescent alcohol abuse and dependence
      (AAD), and adult AAD. Family based association tests were run using Hispanics and
      non-Hispanic European American subjects from two independent longitudinal
      samples. Although the analysis provided nominal support for an association with
      rs9291283 and AAD in adulthood and CD in adolescence, the current study failed to
      replicate previous associations between two well replicated GABRA2 SNPs and CD
      and alcohol dependence. Overall, these results emphasize the utility of including
      an independent replication sample in the study design, so that the results from
      an individual sample can be weighted in the context of its reproducibility. 

PMID- 24687272
TI  - All spraying processes for the fabrication of robust, self-healing,
      superhydrophobic coatings.
AB  - The spraying method is developed for the fabrication of mechanically robust and
      self-healing superhydrophobic coatings, which comprise highly porous and rough
      polyelectrolyte coatings preserved with low-surface-energy healing agents. These
      coatings can repetitively and autonomically restore superhydrophobicity in humid
      environments. After depletion of healing agents, superhydrophobic coatings with
      dual healing agents can regain their self-healing ability by re-spraying
      fluoroalkylsilane. 

PMID- 24687274
TI  - Association between serum soluble low-density lipoprotein receptor levels and
      metabolic factors in healthy Japanese individuals.
AB  - BACKGROUND: Soluble low-density lipoprotein receptor (sLDL-R) is formed by
      cleavage of the extracellular domain of low-density lipoprotein receptor (LDL-R).
      It is unclear whether serum sLDL-R is a marker of diseases associated with
      triglyceride (TG) metabolism. We investigated the association between serum sLDL
      R concentrations and other biochemical parameters in healthy Japanese
      individuals. METHODS: Study subjects consisted of 102 healthy adult Japanese
      volunteers (42 men, 60 women) with body mass index (BMI) < 30 kg/m(2) and serum
      TGs, LDL cholesterol (LDL-C), aspartate aminotransferase, alanine
      aminotransferase, gamma-glutamyl transpeptidase, and glucose concentrations
      within normal ranges. Serum sLDL-R concentrations were determined by enzyme
      linked immunosorbent assay and their correlations with biochemical parameters
      were analyzed. RESULTS: Mean serum sLDL-R concentration was 120.9 +/- 39.9 ng/ml.
      Serum sLDL-R levels were significantly and positively correlated with BMI (rs =
      0.252) and TG (rs = 0.408) and LDL-C (rs = 0.325) concentrations. Multiple
      regression analysis adjusted for age, gender, and smoking showed that BMI (beta =
      0.274), TG (beta = 0.328), and LDL-C (beta = 0.224) were factors independently
      correlated with sLDL-R levels. CONCLUSION: Serum sLDL-R concentration may be a
      marker of diseases associated with TG metabolism. This is the first report to
      date describing the clinical relevance of sLDL-R.

PMID- 24687273
TI  - Continuity in features of anxiety and attention deficit/hyperactivity disorder in
      young preschool children.
AB  - Anxiety disorders and attention deficit/hyperactivity disorder (ADHD) develop
      before school age, but little is known about early developmental pathways. Here
      we test two hypotheses: first, that early signs of anxiety and ADHD at 18 months
      predict symptoms of anxiety and ADHD at age 31/2 years; second, that emotional
      dysregulation at 18 months predicts the outcome of co-occurring anxiety and ADHD
      at age 31/2 years. The study was part of the prospective Norwegian Mother and
      Child Cohort Study (MoBa) at the Norwegian Institute of Public Health. The 628
      participants were clinically assessed at 31/2 years. Questionnaire data collected
      at 18 months were categorized into early behavioural scales of anxiety, ADHD, and
      emotional dysregulation. We investigated continuity in features of anxiety and
      ADHD from 18 months to 31/2 years of age through logistic regression analyses.
      Anxiety symptoms at 31/2 years were predicted by early signs of anxiety (Odds
      ratio (OR) = 1.41, CI = 1.15-1.73) and emotional dysregulation (OR = 1.33, CI =
      1.15-1.54). ADHD symptoms at 31/2 years were predicted by early signs of ADHD (OR
      = 1.51, CI = 1.30-1.76) and emotional dysregulation (OR = 1.31, CI = 1.13-1.51).
      Co-occurring anxiety and ADHD symptoms at 31/2 years were predicted by early
      signs of anxiety (OR = 1.43, CI = 1.13-1.84), ADHD (OR = 1.30, CI = 1.11-1.54),
      and emotional dysregulation (OR = 1.34, CI = 1.13-1.58). We conclude that there
      were modest continuities in features of anxiety and ADHD through early preschool
      years, while emotional dysregulation at age 18 months was associated with
      symptoms of anxiety, ADHD, and co-occurring anxiety and ADHD at age 31/2 years.

PMID- 24687275
TI  - Effects of atrazine on endocrinology and physiology in juvenile barramundi, Lates
      calcarifer (Bloch).
AB  - Exposure to certain environmental contaminants such as agricultural pesticides
      can alter normal endocrine and reproductive parameters in wild fish populations.
      Recent studies have found widespread pesticide contamination across the rivers
      that discharge into the Great Barrier Reef lagoon. Potential impacts on native
      fish species exposed to known endocrine disrupting chemicals such as atrazine,
      simazine, and diuron have not been assessed. In the present study, the authors
      examined the endocrine and physiological effects of short-term, acute exposure of
      environmentally relevant concentrations of analytical grade atrazine in juvenile
      barramundi (Lates calcarifer) in a controlled laboratory experiment. Expression
      of hepatic vitellogenin was not affected, supporting results of previous studies
      that showed that atrazine does not have a direct estrogenic effect via mediation
      of estrogen receptors. The lack of effect on brain cytochrome P19B (CYP19B)
      expression levels, combined with increases in testosterone (T) and 17beta
      estradiol and a stable T:17beta estradiol ratio, does not support the hypothesis
      that atrazine has an indirect estrogenic effect via modulation of aromatase
      expression. Gill ventilation rate, a measure of oxidative stress, did not change
      in contrast to other studies finding enhanced osmoregulatory disturbance and gill
      histopathology after atrazine exposure. To more closely reflect field conditions,
      the authors recommend that laboratory studies should focus more on examining the
      effects of commercial pesticide formulations that contain additional ingredients
      that have been found to be disruptive to endocrine function.

PMID- 24687276
TI  - Melina Schuh: first comes the egg.

PMID- 24687277
TI  - Uniform nomenclature for the mitochondrial contact site and cristae organizing
      system.
AB  - The mitochondrial inner membrane contains a large protein complex that functions
      in inner membrane organization and formation of membrane contact sites. The
      complex was variably named the mitochondrial contact site complex, mitochondrial
      inner membrane organizing system, mitochondrial organizing structure, or
      Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the
      nomenclature and term the complex "mitochondrial contact site and cristae
      organizing system" and its subunits Mic10 to Mic60. 

PMID- 24687278
TI  - Mitochondrial trafficking and anchoring in neurons: New insight and implications.
AB  - Mitochondria are essential organelles for neuronal growth, survival, and
      function. Neurons use specialized mechanisms to drive mitochondria transport and
      to anchor them in axons and at synapses. Stationary mitochondria buffer
      intracellular Ca(2+) and serve as a local energy source by supplying ATP. The
      balance between motile and stationary mitochondria responds quickly to changes in
      axonal and synaptic physiology. Defects in mitochondrial transport are implicated
      in the pathogenesis of several major neurological disorders. Recent work has
      provided new insight in the regulation of microtubule-based mitochondrial
      trafficking and anchoring, and on how mitochondrial motility influences neuron
      growth, synaptic function, and mitophagy. 

PMID- 24687279
TI  - Ensconsin/Map7 promotes microtubule growth and centrosome separation in
      Drosophila neural stem cells.
AB  - The mitotic spindle is crucial to achieve segregation of sister chromatids. To
      identify new mitotic spindle assembly regulators, we isolated 855 microtubule
      associated proteins (MAPs) from Drosophila melanogaster mitotic or interphasic
      embryos. Using RNAi, we screened 96 poorly characterized genes in the Drosophila
      central nervous system to establish their possible role during spindle assembly.
      We found that Ensconsin/MAP7 mutant neuroblasts display shorter metaphase
      spindles, a defect caused by a reduced microtubule polymerization rate and
      enhanced by centrosome ablation. In agreement with a direct effect in regulating
      spindle length, Ensconsin overexpression triggered an increase in spindle length
      in S2 cells, whereas purified Ensconsin stimulated microtubule polymerization in
      vitro. Interestingly, ensc-null mutant flies also display defective centrosome
      separation and positioning during interphase, a phenotype also detected in
      kinesin-1 mutants. Collectively, our results suggest that Ensconsin cooperates
      with its binding partner Kinesin-1 during interphase to trigger centrosome
      separation. In addition, Ensconsin promotes microtubule polymerization during
      mitosis to control spindle length independent of Kinesin-1. 

PMID- 24687280
TI  - Complexin synchronizes primed vesicle exocytosis and regulates fusion pore
      dynamics.
AB  - ComplexinII (CpxII) and SynaptotagminI (SytI) have been implicated in regulating
      the function of SNARE proteins in exocytosis, but their precise mode of action
      and potential interplay have remained unknown. In this paper, we show that CpxII
      increases Ca(2+)-triggered vesicle exocytosis and accelerates its secretory
      rates, providing two independent, but synergistic, functions to enhance
      synchronous secretion. Specifically, we demonstrate that the C-terminal domain of
      CpxII increases the pool of primed vesicles by hindering premature exocytosis at
      submicromolar Ca(2+) concentrations, whereas the N-terminal domain shortens the
      secretory delay and accelerates the kinetics of Ca(2+)-triggered exocytosis by
      increasing the Ca(2+) affinity of synchronous secretion. With its C terminus,
      CpxII attenuates fluctuations of the early fusion pore and slows its expansion
      but is functionally antagonized by SytI, enabling rapid transmitter discharge
      from single vesicles. Thus, our results illustrate how key features of CpxII,
      SytI, and their interplay transform the constitutively active SNARE-mediated
      fusion mechanism into a highly synchronized, Ca(2+)-triggered release apparatus. 

PMID- 24687283
TI  - Scanning electron microscopy of all parasitic stages of Haemaphysalis
      qinghaiensis Teng, 1980 (Acari: Ixodidae).
AB  - Haemaphysalis qinghaiensis Teng (Acta Zootaxon Sin 5:144-149, 1980) is an endemic
      species in China. This tick species was first described based on engorged or semi
      engorged specimens, and the drawings and description in words of morphological
      characteristics were poor. Therefore, the present study aims to redescribe
      morphological characteristics of all active stages of this tick species in detail
      by scanning electron microscopy. Additionally, a comparison between H.
      qinghaiensis and other sympatric Haemaphysalis species was also analyzed. Males
      of H. qinghaiensis can be distinguished from sympatric Haemaphysalis species by
      the following characters: palpi less salient laterally and curved in contour;
      ventrointernal setae of palpal segment II thin, number <7; the tips of palpal
      segment III not so strongly recurved inward to become "pincerlike" and lacking
      dorsal spur; dental formula 5/5; lateral grooves enclose first festoon; coxa IV
      with a short, broadly triangular spur; tarsi somewhat humped; and spiracular
      plates long comma-shaped. Females of H. qinghaiensis can be distinguished by
      palpi less salient laterally and curved in contour; ventrointernal setae of
      palpal segment II thin, number <7; segment III of palpi lacking dorsal spur;
      dental formula 4/4; scutum subcircula; and tarsi somewhat humped. Nymphs of H.
      qinghaiensis can be distinguished from those of other species by palpi less
      salient laterally and curved in contour; dental formula 2/2; basis capituli
      rectangular, with distinct dorsal cornua, without ventral cornua; and spiracular
      plates with short and narrow dorsal prolongation. Larvae of H. qinghaiensis can
      be distinguished by palpi less salient laterally and curved in contour; basis
      capituli rectangular, without distinct cornua. 

PMID- 24687282
TI  - Development of an immunomagnetic bead separation-coupled quantitative PCR method
      for rapid and sensitive detection of Cryptosporidium parvum oocysts in calf
      feces.
AB  - Cattle feces are the environmental vehicle for the zoonotic Cryptosporidium
      oocysts, but there are drawbacks associated with reliability of the existing
      methods for the detection of oocysts in the feces. Quantification of the
      immunomagnetic bead separation (IMS) coupled with real-time TaqMan PCR (qPCR) was
      accomplished by comparing the fluorescence signals obtained from the calf fecal
      samples of Cryptosporidium parvum oocysts with those obtained from standard
      dilutions of C. parvum oocysts. TaqMan qPCR assays were developed for the
      detection of C. parvum based on 18S rDNA gene. This IMS-qPCR assay allowed a
      reliable quantification of C. parvum oocysts over seven orders of magnitude with
      a baseline sensitivity of 8.7 oocysts. The newly developed IMS-qPCR technique
      proved specific as confirmed by negative reactivity against a wide panel of non
      parvum Cryptosporidium oocysts. As a field application, experimentally infected
      calves (15 infected and 9 non-infected) were screened for oocysts shedding on 16,
      18, and 21 days postinfection. Acid-fast staining microscopy of infected calves
      revealed oocysts in the feces of 11, 7, and 4 calves, respectively, compared to
      15, 15, and 12 in case of screening by IMS-qPCR. Taken together, the proposed IMS
      qPCR method significantly improved the diagnostic capacity for C. parvum
      infection in calves, making the technique a useful, sensitive, reliable, and time
      saving. 

PMID- 24687281
TI  - Functionally distinct PI 3-kinase pathways regulate myelination in the peripheral
      nervous system.
AB  - The PI 3-kinase (PI 3-K) signaling pathway is essential for Schwann cell
      myelination. Here we have characterized PI 3-K effectors activated during
      myelination by probing myelinating cultures and developing nerves with an
      antibody that recognizes phosphorylated substrates for this pathway. We
      identified a discrete number of phospho-proteins including the S6 ribosomal
      protein (S6rp), which is down-regulated at the onset of myelination, and N-myc
      downstream-regulated gene-1 (NDRG1), which is up-regulated strikingly with
      myelination. We show that type III Neuregulin1 on the axon is the primary
      activator of S6rp, an effector of mTORC1. In contrast, laminin-2 in the
      extracellular matrix (ECM), signaling through the alpha6beta4 integrin and Sgk1
      (serum and glucocorticoid-induced kinase 1), drives phosphorylation of NDRG1 in
      the Cajal bands of the abaxonal compartment. Unexpectedly, mice deficient in
      alpha6beta4 integrin signaling or Sgk1 exhibit hypermyelination during
      development. These results identify functionally and spatially distinct PI 3-K
      pathways: an early, pro-myelinating pathway driven by axonal Neuregulin1 and a
      later-acting, laminin-integrin-dependent pathway that negatively regulates
      myelination. 

PMID- 24687284
TI  - Protostrongylus pulmonalis (Frolich, 1802) and P. oryctolagi Babos, 1955
      (Nematoda: Protostrongylidae), parasites of the lungs of European hare (Lepus
      europaeus L.) in France: morphological and molecular approaches.
AB  - Pulmonary protostrongyliasis of hare is a parasitic disease caused by nematodes
      belonging to the genus Protostrongylus (Nematoda, Protostrongylidae). During
      survey of wildlife disease in the South-East of France, pathologic examination of
      lungs from European hares found dead or hunter-killed between 2009 and 2012 was
      performed. Adult male worms were morphologically characterized and the
      identification confirmed by molecular biology (D2 domain of the 28S and ITS2 of
      rDNA). Two different species were identified: the first one, Protostrongylus
      pulmonalis, is identical with the haplotype previously deposited in GenBank.
      Based on morphological criteria of copulatory bursa of adult male worms
      (especially length of spicules and gubernaculum structure), we identified a
      second species found in France as Protostrongylus oryctolagi. This is the first
      report of P. oryctolagi in France from European hare and rabbit. P. oryctolagi
      was isolated from 248 hares and 3 rabbits in the South of France. P. pulmonalis
      was isolated from four hares found dead in the Northern France and from one hare
      in the South, which was co-parasitized by P. oryctolagi and P. pulmonalis. It's
      the first coinfection observed with these two species from a lung of hare in
      France. 

PMID- 24687285
TI  - The enigmatic role of cholinergic reflex in the pathogenesis of Chagas disease.
AB  - This study evaluated the inflammatory process in the colons of mice infected with
      Trypanosoma cruzi QM2 strain, through the analysis of muscle reactivity and the
      measurement of butyrylcholinesterase (BuChE) in plasma. "Swiss" mice were
      infected with T. cruzi QM2 strain and after 15 (G15), 30 (G30), 60 (G60), 90
      (G90), and 210 (G210) days, each group had blood collected for the measurement of
      butyrylcholinesterase plasma concentrations ([BuChE]), a measure which functioned
      as an indicator of plasmatic Ach levels. All groups, except G15, had a segment of
      proximal colon removed to assess muscle reactivity to acetylcholine (Ach) and
      noradrenaline (NA) stimulation. After reactivity tests, the tissues were then
      fixed and stained with hematoxylin and eosin (HE) for histological evaluation of
      inflammatory response. The QM2 strain did induce inflammatory process in mice
      colon, and demonstrated differences in muscular contraction between the G60 and
      G210 groups, with p < 0.05. Plasma [BuChE] increased during the acute phase of
      infection (p < 0.05) with subsequent heterogeneous decline in the late chronic
      phase. These results show that the QM2 strain has tropism to the colon of mice
      and causes damage characteristic of megacolon; also, Ach has an enigmatic
      importance in the anti-inflammatory reflex over the course of T. cruzi infection.

PMID- 24687286
TI  - Echinococcus multilocularis infections in dogs from urban and peri-urban areas in
      France.
AB  - Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a
      severe zoonotic disease. It is maintained through a sylvatic life cycle based on
      predator-prey interactions mainly between foxes and rodents. Dogs are also good
      definitive hosts; and due to their close proximity to humans, they may represent
      a major risk factor for the occurrence of human cases. In two medium-sized cities
      of Eastern France (Annemasse and Pontarlier), located in highly endemic areas,
      817 dog feces samples were collected and analyzed by a flotation technique
      followed by a multiplex PCR assay. For the first time in France, we assessed the
      presence of E. multilocularis DNA in four dog feces samples, in which it
      represents an estimated prevalence of 0.5% (95% CI; 0.1% <> 1.3%). Eight other
      samples presented taeniid infections from three different species (Taenia
      crassiceps, Taenia serialis, and Taenia polyacantha). When considering both E.
      multilocularis and Taenia sensu lato, prevalence rose to 0.6% in Annemasse and
      2.6% in Pontarlier. In this highly endemic context, proper application of the
      usual deworming recommendations (70% of the dogs were treated twice a year or
      more) failed to prevent dog infection, particularly for hunting dogs. Our results
      stressed the need to adapt treatment to the environmental context and to the
      specific activity of dogs. Further epidemiological surveys in domestic dogs and
      cats using this coprological approach are still needed to obtain a better
      overview of infection and the associated zoonotic risk.

PMID- 24687287
TI  - Determination of swertianolin in rat plasma by LC-MS/MS and its application to a
      pharmacokinetic study.
AB  - A sensitive and rapid LC-MS/MS method has been developed and validated for
      quantifying swertianolin in rat plasma using rutin as an internal standard (IS).
      Following liquid-liquid extraction with ethyl acetate, chromatographic separation
      for swertianolin was achieved on a C18 column with a gradient elution using 0.1%
      formic acid as mobile phase A and acetonitrile as mobile phase B at a flow rate
      of 0.3 mL/min. The detection was performed on a tandem mass spectrometer using
      multiple reaction monitoring via an electrospray ionization source and operating
      in the negative ionization mode. The optimized mass transition ion pairs (m/z)
      for quantitation were 435.1/272.0 for swertianolin and 609.2/300.1 for IS. The
      lower limit of quantitation was 0.5 ng/mL within a linear range of 0.5-500 ng/mL.
      Intra-day and inter-day precision was less than 6.8%. The accuracy was in the
      range of -13.9 to 12.0%. The mean recovery of swertianolin was >66.7%. The
      proposed method was successfully applied in evaluating the pharmacokinetics of
      swertianolin after an oral dose of 50 mg/kg Swertia mussotii extract in rats.

PMID- 24687288
TI  - A heart-breaking case of fever and rash.

PMID- 24687289
TI  - Implementation Science Workshop: primary care-based multidisciplinary readmission
      prevention program.

PMID- 24687291
TI  - The CMS Innovation Center: delivering on the promise of payment and delivery
      reform.

PMID- 24687292
TI  - Structuring payment to medical homes after the affordable care act.
AB  - The Patient-Centered Medical Home (PCMH) is a leading model of primary care
      reform, a critical element of which is payment reform for primary care services.
      With the passage of the Affordable Care Act, the Accountable Care Organization
      (ACO) has emerged as a model of delivery system reform, and while there is
      theoretical alignment between the PCMH and ACOs, the discussion of physician
      payment within each model has remained distinct. Here we compare payment for
      medical homes with that for accountable care organizations, consider
      opportunities for integration, and discuss implications for policy makers and
      payers considering ACO models. The PCMH and ACO are complementary approaches to
      reformed care delivery: the PCMH ultimately requires strong integration with
      specialists and hospitals as seen under ACOs, and ACOs likely will require a high
      functioning primary care system as embodied by the PCMH. Aligning payment
      incentives within the ACO will be critical to achieving this integration and
      enhancing the care coordination role of primary care in these settings. 

PMID- 24687293
TI  - Capsule commentary on Gonzalo et al., Patient-centered interprofessional
      collaborative care: factors associated with bedside interprofessional rounds.

PMID- 24687295
TI  - Combined D2-/L2-hydroxyglutaric aciduria (SLC25A1 deficiency): clinical course
      and effects of citrate treatment.
AB  - Combined D,L-2-hydroxyglutaric aciduria (DL-2HGA; OMIM #615182) is a rare
      neurometabolic disorder clinically characterized by muscular hypotonia, severe
      neurodevelopmental dysfunction, and intractable seizures associated with
      respiratory distress. Biochemically, DL-2HGA patients excrete increased amounts
      of D- and L-2-hydroxyglutarate (D2HG and L2HG, respectively), with predominance
      of D2HG, and alpha-ketoglutarate, and show a decrease in urinary citrate.
      Impaired function of the mitochondrial citrate carrier (CIC) due to pathogenic
      mutations within the SLC25A1 gene has been identified as the underlying molecular
      cause of the disease. CIC mediates efflux of the mitochondrial tricarboxylic acid
      (TCA) cycle intermediates citrate and isocitrate in exchange for cytosolic
      malate. Thus, depletion of cytosolic citrate as well as accumulation of citrate
      inside mitochondria have been considered to play a role in the pathophysiology of
      DL-2HGA. Here, we report for the first time on a patient with a genetically
      confirmed diagnosis of DL-2HGA and treatment with either malate or citrate.
      During malate treatment, urinary malate concentration increased, but beyond that,
      neither biochemical nor clinical alterations were observed. In contrast,
      treatment with citrate led to an increased urinary excretion of TCA cycle
      intermediates malate and succinate, and by trend to an increased concentration of
      urinary citrate. Furthermore, excretion of D2HG and L2HG was reduced during
      citrate treatment. Clinically, the patient showed stabilization with regard to
      frequency and severity of seizures. Treating DL-2HGA with citrate should be
      considered in other DL-2HGA patients, and its effects should be studied
      systematically. 

PMID- 24687294
TI  - Innovative strategies to treat protein misfolding in inborn errors of metabolism:
      pharmacological chaperones and proteostasis regulators.
AB  - To attain functionality, proteins must fold into their three-dimensional native
      state. The intracellular balance between protein synthesis, folding, and
      degradation is constantly challenged by genetic or environmental stress factors.
      In the last ten years, protein misfolding induced by missense mutations was
      demonstrated to be the seminal molecular mechanism in a constantly growing number
      of inborn errors of metabolism. In these cases, loss of protein function results
      from early degradation of missense-induced misfolded proteins. Increasing
      knowledge on the proteostasis network and the protein quality control system with
      distinct mechanisms in different compartments of the cell paved the way for the
      development of new treatment strategies for conformational diseases using small
      molecules. These comprise proteostasis regulators that enhance the capacity of
      the proteostasis network and pharmacological chaperones that specifically bind
      and rescue misfolded proteins by conformational stabilization. They can be used
      either alone or in combination, the latter to exploit synergistic effects. Many
      of these small molecule compounds currently undergo preclinical and clinical
      pharmaceutical development and two have been approved: saproterin dihydrochloride
      for the treatment of phenylketonuria and tafamidis for the treatment of
      transthyretin-related hereditary amyloidosis. Different technologies are
      exploited for the discovery of new small molecule compounds that belong to the
      still young class of pharmaceutical products discussed here. These compounds may
      in the near future improve existing treatment strategies or even offer a first
      time treatment to patients suffering from nowadays-untreatable inborn errors of
      metabolism. 

PMID- 24687296
TI  - Cloning and characterization of a novel fold-type I branched-chain amino acid
      aminotransferase from the hyperthermophilic archaeon Thermococcus sp. CKU-1.
AB  - We successfully cloned a novel branched-chain amino acid aminotransferase (Ts
      BcAT; EC 2.6.1.42) gene from the Thermococcus sp. CKU-1 genome and expressed it
      in the soluble fraction of Escherichia coli Rosetta (DE3) cells. Ts-BcAT is a
      homodimer with an apparent molecular mass of approximately 92 kDa. The primary
      structure of Ts-BcAT showed high homology with the fold-type I, subgroup I
      aminotransferases, but showed little homology with BcATs known to date, i.e.,
      those of Escherichia coli and Salmonella typhimurium, which belong to the fold
      type IV, subgroup III aminotransferases. The maximum enzyme activity of Ts-BcAT
      was detected at 95  degrees C, and Ts-BcAT did not lose any enzyme activity, even
      after incubation at 90  degrees C for 5 h. Ts-BcAT was active in the pH range
      from 4.0 to 11.0, the optimum pH was 9.5, and the enzyme was stable between pH 6
      and 7. The exceptionally low pK a of the nitrogen atom in the Lys258 epsilon
      amino group in the internal aldimine bond of Ts-BcAT was determined to be 5.52 +/
      0.05. Ts-BcAT used 21 natural and unnatural amino acids as a substrate in the
      overall transamination reaction. L-Leucine and other aliphatic amino acids are
      efficient substrates, while polar amino acids except glutamate were weak
      substrates. Phylogenetic analysis revealed that Ts-BcAT is a novel fold-type I,
      subgroup I branched-chain aminotransferase.

PMID- 24687297
TI  - What's new in ICU visiting policies: can we continue to keep the doors closed?

PMID- 24687298
TI  - Predictors of insufficient amikacin peak concentration in critically ill patients
      receiving a 25 mg/kg total body weight regimen.
AB  - PURPOSE: Amikacin requires pharmacodynamic targets of peak serum concentration
      (Cmax) of 8-10 times the minimal inhibitory concentration, corresponding to a
      target Cmax of 60-80 mg/L for the less susceptible bacteria. Even with new dosing
      regimens of 25 mg/kg, 30% of patients do not meet the pharmacodynamic target. We
      aimed to identify predictive factors for insufficient Cmax in a population of
      critically ill patients. METHODS: Prospective observational monocentric study of
      patients admitted to a general ICU and requiring a loading dose of amikacin.
      Amikacin was administered intravenously at the dose of 25 mg/kg of total body
      weight. Independent determinants of Cmax < 60 mg/L were identified by mixed model
      multivariate analysis. RESULTS: Over a 1-year period, 181 episodes in 146
      patients (SAPS 2 = 51 [41-68]) were included. At inclusion, the SOFA score was 8
      [6-12], 119 (66%) episodes required vasopressors, 150 (83%) mechanical
      ventilation, and 81 (45%) renal replacement therapy. The amikacin Cmax was 69
      [54.9-84.4] mg/L. Overall, 60 (33%) episodes had a Cmax < 60 mg/L. The risk of
      Cmax < 60 mg/L associated with BMI < 25 kg/m(2) varied across quarters of
      inclusion. Independent risk factors for Cmax < 60 mg/L were a BMI < 25 kg/m(2)
      over the first quarter (odds ratio (OR) 15.95, 95% confidence interval (CI) [3.68
      69.20], p < 0.001) and positive 24-h fluid balance (OR per 250-mL increment 1.06,
      95% [CI 1.01-1.11], p = 0.018). CONCLUSIONS: Despite an amikacin dose of 25 mg/kg
      of total body weight, 33% of patients still had an amikacin Cmax < 60 mg/L.
      Positive 24-h fluid balance was identified as a predictive factor of Cmax < 60
      mg/L. When total body weight is used, low BMI tended to be associated with
      amikacin underdosing. These results suggest the need for higher doses in patients
      with a positive 24-h fluid balance in order to reach adequate therapeutic
      targets.

PMID- 24687299
TI  - A pilot study of associations between treatment for anorexia nervosa and carers'
      distress.
AB  - In order to investigate the degree to which symptom reduction in the treatment of
      adults with anorexia nervosa (AN) impacted on their carers' psychological
      distress, we examined 12 participants in an outpatient treatment trial and their
      nominated 'significant other'. Measures of eating psychopathology in the person
      being treated for AN were collected on six occasions: baseline, session 4,
      session 10, session 25 (end of treatment), and at three-month and 12-month follow
      up. At these same time points, measures of psychological distress were collected
      from carers. Early significant reductions in eating psychopathology were found in
      the AN group at session 4, whereas significant reductions in carers' distress
      were found at three-month follow-up and maintained at 12-month follow-up. These
      reductions were moderated by baseline body mass index of the person with AN.
      Carers whose significant other had a lower BMI at baseline received most benefit
      in terms of symptom reduction at 12-month follow-up. Clinical implications
      include the need to provide more direct support to carers in order to achieve
      more clinically significant reductions in distress, and the need to discuss a
      carer's expectations of the recovery process. KEY PRACTITIONER MESSAGE: Only 61%
      of adults being treated for anorexia nervosa (AN) were willing to allow their
      carer to be contacted by researchers in order to ask them to complete
      questionnaires over the duration of treatment and follow-up. Significant
      reductions in eating psychopathology from those being treated for AN was followed
      by significant reductions in their carers' distress some 12 months later.
      Reductions of carers' distress was associated with only a small effect size and
      may indicate that more clinically significant reductions requires individualised
      support for the carers. Carers whose significant other had a lower body mass
      index at baseline received most benefit in terms of symptom reduction at 12-month
      follow-up, which may indicate a need to clarify a carer's expectations of the
      recovery process.

PMID- 24687300
TI  - Heart failure and dipeptidyl peptidase-4 inhibitors.

PMID- 24687301
TI  - Peripheral blood stem cell mobilization and engraftment after autologous stem
      cell transplantation with biosimilar rhG-CSF.
AB  - INTRODUCTION: Biosimilar versions of filgrastim [recombinant human granulocyte
      colony-stimulating factor (rhG-CSF)] are now widely available. To date,
      biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy
      profile to the originator product (filgrastim [Neupogen((r))], Amgen Inc., CA,
      USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have
      also been used to induce peripheral blood stem cell (PBSC) mobilization in
      patients undergoing autologous stem cell transplantation (AHSCT). The authors
      have examined the effectiveness of a biosimilar rhG-CSF (Zarzio((r)), Sandoz
      Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two
      medical centers in Hungary. METHODS: In Study 1, 70 patients with hematological
      malignancies scheduled to undergo AHSCT received chemotherapy followed by
      biosimilar rhG-CSF (2 * 5 MUg) for facilitating neutrophil, leukocyte, and
      platelet engraftment. In study 2, 40 additional patients with lymphoid
      malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG
      CSF for PBSC mobilization. The effectiveness of treatment was assessed by the
      average yield of cluster of differentiation (CD) 34+ cells and the number of
      leukaphereses required. RESULTS: In Study 1 (patients undergoing AHSCT), the
      median age was 56 years and most patients were male (60%). The conditioning
      regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU((r)),
      Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n =
      21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range
      8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment
      was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and
      the majority (57.5%) were female. The median time interval between day 1 of
      mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the
      autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 *
      10(6)/kg (2.22-57.07 * 10(6)/kg). The median yield of CD34+ cells per
      leukapheresis product was 2.47 * 10(6)/kg. In total, 58 leukaphereses were
      performed in 40 successfully harvested patients. CONCLUSIONS: In line with
      previous studies with originator rhG-CSF, the findings of this study indicate
      that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated
      in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the
      originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+
      cells. In conclusion, the authors have demonstrated that the use of biosimilar
      rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment
      after AHSCT.

PMID- 24687302
TI  - In reference to What are the best management strategies for radiation-induced
      xerostomia?

PMID- 24687303
TI  - Open source software implementation of an integrated testing strategy for skin
      sensitization potency based on a Bayesian network.
AB  - An open-source implementation of a previously published integrated testing
      strategy (ITS) for skin sensitization using a Bayesian network has been developed
      using R, a free and open-source statistical computing language. The ITS model
      provides probabilistic predictions of skin sensitization potency based on in
      silico and in vitro information as well as skin penetration characteristics from
      a published bioavailability model (Kasting et al., 2008). The structure of the
      Bayesian network was designed to be consistent with the adverse outcome pathway
      published by the OECD (Jaworska et al., 2011, 2013). In this paper, the
      previously published data set (Jaworska et al., 2013) is improved by two data
      corrections and a modified application of the Kasting model. The new data set
      implemented in the original commercial software package and the new R version
      produced consistent results. The data and a fully documented version of the code
      are publicly available (http://ntp.niehs.nih.gov/go/its).

PMID- 24687304
TI  - Exogenous hydrogen sulfide alleviates high glucose-induced cardiotoxicity via
      inhibition of leptin signaling in H9c2 cells.
AB  - Hydrogen sulfide (H2S) protects cardiomyoblasts against high glucose (HG)-induced
      injury by inhibiting the activation of p38 mitogen-activated protein kinase
      (MAPK). This study aims to determine whether the leptin-p38 MAPK pathway is
      involved in HG-induced injury and whether exogenous H2S prevents the HG-induced
      insult through inhibition of the leptin-p38 MAPK pathway in H9c2 cells. H9c2
      cells were treated with 35 mM glucose (HG) for 24 h to establish a HG-induced
      cardiomyocyte injury model. Cell viability; mitochondrial membrane potential
      (DeltaPsi m); apoptosis; reactive oxygen species (ROS) level; and leptin, leptin
      receptor, and p38 MAPK expression level were measured by the methods indicated.
      The results showed pretreatment of H9c2 cells with NaHS before exposure to HG led
      to an increase in cell viability, decrease in apoptotic cells, ROS generation,
      and a loss of DeltaPsi m. Exposure of H9c2 cells to 35 mM glucose for 24 h
      significantly upregulated the expression levels of leptin and leptin receptors.
      The increased expression levels of leptin and leptin receptors were markedly
      attenuated by pretreatment with 400 MUM NaHS. In addition, the HG-induced
      increase in phosphorylated (p) p38 MAPK expression was ameliorated by
      pretreatment with 50 ng/ml leptin antagonist. In conclusion, the present study
      has demonstrated for the first time that the leptin-p38 MAPK pathway contributes
      to the HG-induced injury in H9c2 cells and that exogenous H2S protects H9c2 cells
      against HG-induced injury at least in part by inhibiting the activation of leptin
      p38 MAPK pathway.

PMID- 24687305
TI  - Maslinic acid induced apoptosis in bladder cancer cells through activating p38
      MAPK signaling pathway.
AB  - Bladder cancer is among the most aggressive human malignant carcinoma and always
      showed resistance to traditional chemotherapy based on DNA damaging drugs. Unlike
      the existing drugs that damage nuclear acid molecules, maslinic acid (MA)
      displays anti-tumor function in various types of cancers by targeting specific
      intracellular signaling pathways and is regarded as a promising agent for future
      clinical cancer therapy. However, its effect on bladder cancer is still unknown.
      In this study, we assessed the influence of MA on survival of bladder cancer
      cells and the involved mechanisms. MTT assay showed that MA suppressed the
      viability of bladder cancer cells. We further confirmed the growth-suppressing
      activity of MA on T24 and 253J xenograft tumor in mouse models. Subsequently, we
      found that MA induced apoptosis in bladder cancer cells. Based on immunoblotting
      assay, we determined that p38 MAPK pathway was greatly activated in MA-treated
      bladder cancer cells. SB203580 inhibition of p38 MAPK rescued the MA-induced
      apoptosis of bladder cancer cells. In conclusion, we provided evidences that MA
      efficiently suppressed activation of p38 MAPK pathways and induced apoptosis of
      bladder cancer cells. 

PMID- 24687306
TI  - Cell turnover in the repopulated rat liver: distinct lineages for hepatocytes and
      the biliary epithelium.
AB  - The dynamics of cell renewal in the normal adult liver remains an unresolved
      issue. We investigate the possible contribution of a common biliary precursor
      cell pool to hepatocyte turnover in the chimeric long-term repopulated rat liver.
      The retrorsine (RS)-based model of massive liver repopulation was used. Animals
      not expressing the CD26 marker (CD26(-)) were injected with RS, followed by
      transplantation of 2 million syngeneic hepatocytes isolated from a normal CD26
      expressing donor. Extensive (80-90%) replacement of resident parenchymal cells
      was observed at 1 year post-transplantation and persisted at 2 years, as
      expected. A panel of specific markers, including cytokeratin 7, OV6, EpCAM,
      claudin 7 and alpha-fetoprotein, was employed to locate the in situ putative
      progenitor and/or biliary epithelial cells in the stably repopulated liver. No
      overlap was observed between any of these markers and the CD26 tag identifying
      transplanted cells. Exposure to RS was not inhibitory to the putative progenitor
      and/or biliary epithelial cells, nor did we observe any evidence of cell fusion
      between these cells and the transplanted cell population. Given the long-term (>2
      years) stability of the donor cell phenotype in this model of liver repopulation,
      the present findings suggest that hepatocyte turnover in the repopulated liver is
      fuelled by a cell lineage distinct from that of the biliary epithelium and relies
      largely on the differentiated parenchymal cell population. These results support
      the solid biological foundation of liver repopulation strategies based on the
      transplantation of isolated hepatocytes.

PMID- 24687307
TI  - Performances of capillary electrophoresis and HPLC methods in HbA1c
      determination: diagnostic accuracy in HbS and HbD-Iran variants' presence.
AB  - BACKGROUND: Glycated hemoglobin (HbA1c) provides a useful estimate of mean
      glycemia in patients with diabetes and is directly related to risks for diabetes
      complications. The aim of this study is to compare a capillary electrophoresis
      method and two high-performance liquid chromatography (HPLC) cation-exchange
      analyzers (Variant II (Bio-Rad Laboratories, Inc., Hercules, CA) and G8 (Tosoh
      Biosciences, San Francisco, CA)) to identify the most reliable method in Hb
      variants' presence. METHODS: Measurements of HbA1c were carried out in blood
      samples from 200 Tor Vergata Hospital patients, using G8 Tosoh, and from 107 San
      Filippo Neri Hospital patients, using Variant II Bio-Rad methods. All samples
      were analyzed by Capillarys 2 Flex Piercing (FP; Sebia, Lisses, France). RESULTS:
      There was a good concordance between the results of capillary electrophoresis and
      HPLC methods (R(2) = 0.99, P < 0.0001 for G8 HPLC; R(2) = 0.99, P < 0.0001 for
      Variant II HPLC). During the study, we observed that some Hb variants, HbS and
      HbD-Iran, can alter the HbA1c level. CONCLUSIONS: Since the HbA1c test is now
      recommended for diagnosing diabetes, and minimal variation of the concentration
      affects the clinical therapy, it is very important that the results are reliable
      and interference-free. Capillarys 2-FP analyzer is suitable for this purpose and
      sometimes it showed some advantages with respect to the HPLC analyzers tested,
      especially when Hb variants are present.

PMID- 24687308
TI  - Ridge localizations and networks in thin films compressed by the incremental
      release of a large equi-biaxial pre-stretch in the substrate.
AB  - Two-dimensional ridge structures are induced by equi-biaxial compression with
      large equi-biaxial pre-stretch in a thin film by using a micro-fluidics
      technique. Whereas wrinkles tend to be uniformly distributed, ridges are
      localized. The wrinkle-to-ridge transition is unstable (subcritical), resulting
      in large amplitude changes. The nature and morphology of the ridges is studied
      and quantified by experiments and numerical simulations. 

PMID- 24687309
TI  - CH-pi interaction in VQIVYK sequence elucidated by NMR spectroscopy is essential
      for PHF formation of tau.
AB  - One of the histopathological features of Alzheimer's disease (AD) is higher order
      neurofibrillary tangles formed by abnormally aggregated tau protein.
      Investigation of the mechanism of tau aggregation is important for the clarifying
      the cause of AD and the development of therapeutic drugs. The microtubule-binding
      domain, which consists of repeats of similar amino acids (R1-R4) is thought to
      form the core component of paired helical filament (PHF). The hexapeptide(306)
      VQIVYK(311) of R3 has been shown to take a key role of promoting tau aggregation
      and assumed that its CH-pi interaction between the side chains of Ile308 and
      Tyr310 would contribute in stabilizing the filament. In this work, we
      investigated a short isoform of tau (4RTau), R3, VQIVYK peptide and their mutants
      by thioflavin S (ThS) fluorescence, and NMR measurements, and proved for the
      first time that this CH-pi interaction stabilizes the filament at the atomic
      level. In addition, by molecular modeling, we revealed that this interaction
      further supports an extended amphipathic structure for molecular self-association
      during the process of PHF formation of tau protein. The present work indicates
      new approach that inhibits the CH-pi interaction for developing a therapeutic
      agent for AD.

PMID- 24687311
TI  - Evidence of second-trimester changes in head biometry and brain perfusion in
      fetuses with congenital heart disease.
AB  - OBJECTIVES: To evaluate the associations between congenital heart disease (CHD)
      and head biometry and cerebrovascular blood flow dynamics at the time of
      diagnosis of CHD in the second trimester of pregnancy. METHODS: This was a study
      of 95 consecutive fetuses diagnosed with CHD. At the time of diagnosis, fetal
      biometry was performed and brain perfusion was assessed by middle cerebral artery
      pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and fractional moving
      blood volume (FMBV). The results were compared with those of 95 normal fetuses
      matched for gestational age. RESULTS: Median gestational age at diagnosis was 22
      + 3 (range, 20 + 0 to 23 + 5) weeks. Fetuses with CHD showed significantly lower
      MCA-PI and CPR Z-scores (-0.23 vs 0.34 and -0.37 vs 0.30, respectively; both P <
      0.001) and higher FMBV Z-scores (2.35 vs 0.15; P < 0.001). FMBV > 95(th)
      percentile was observed in 81.1% of cases as compared with 10.5% in controls (P <
      0.001). Moreover, cases showed significantly smaller biparietal diameter (BPD)
      and head circumference (HC) Z-scores (-1.61 vs -0.43 and -0.89 vs 0.09,
      respectively; both P < 0.001), with a higher proportion of BPD and HC
      measurements below the 5(th) percentile compared with controls (51.6% vs 13.7%
      and 26.3% vs 4.2%, respectively; both P < 0.001). These findings were more
      pronounced in those cases with types of CHD associated with compromised
      oxygenated blood delivery to the brain, such as left outflow tract obstruction
      and transposition of the great arteries. CONCLUSIONS: A high proportion of
      fetuses with CHD have a smaller head and increased brain perfusion already in the
      second trimester, suggesting an early onset of the mechanisms leading to poorer
      neurodevelopment later in life.

PMID- 24687310
TI  - Trends in inappropriate drug therapy prescription in the elderly in Sweden from
      2006 to 2013: assessment using national indicators.
AB  - BACKGROUND: Medication for elderly patients is often complex and problematic.
      Several criteria for classifying inappropriate prescribing exist. In 2010, the
      Swedish National Board of Health and Welfare published the document "Indicators
      of appropriate drug therapy in the elderly" as a guideline for improving
      prescribing for the elderly. OBJECTIVE: The aim of this study was to assess
      trends in the prescription of inappropriate drug therapy in the elderly in Sweden
      from 2006 to 2013 using national quality indicators for drug treatment. METHODS:
      Individual-based data on dispensed prescription drugs for the entire Swedish
      population aged >=65 years during eight 3-month periods from 2006 to 2013 were
      accumulated. The data were extracted from the Swedish Prescribed Drug Register.
      Eight drug-specific quality indicators were monitored. RESULTS: For the entire
      population studied (n = 1,828,283 in 2013), six of the eight indicators showed an
      improvement according to the guidelines; the remaining two indicators (drugs with
      anticholinergic effects and excessive polypharmacy) remained relatively
      unchanged. For the subgroup aged 65-74 years, three indicators showed an
      improvement, four indicators remained relatively unchanged (e.g. propiomazine,
      and oxazepam) and one showed an undesirable trend (anticholinergic drugs)
      according to guidelines. For the older group (aged >=75 years), all indicators
      except excessive polypharmacy showed improvement. CONCLUSION: According to the
      quality indicators used, the extent of inappropriate drug therapy in the elderly
      decreased from 2006 to 2013 in Sweden. Thus, prescribers appear to be more likely
      to change their prescribing patterns for the elderly than previously assumed.

PMID- 24687312
TI  - Bladder cancer in women.

PMID- 24687314
TI  - Trap of trends to statistical significance: likelihood of near significant P
      value becoming more significant with extra data.

PMID- 24687315
TI  - After eradication: India's post-polio problem.

PMID- 24687313
TI  - Selective digestive or oropharyngeal decontamination and topical oropharyngeal
      chlorhexidine for prevention of death in general intensive care: systematic
      review and network meta-analysis.
AB  - OBJECTIVES: To determine the effect on mortality of selective digestive
      decontamination, selective oropharyngeal decontamination, and topical
      oropharyngeal chlorhexidine in adult patients in general intensive care units and
      to compare these interventions with each other in a network meta-analysis.
      DESIGN: Systematic review, conventional meta-analysis, and network meta-analysis.
      Medline, Embase, and CENTRAL were searched to December 2012. Previous meta
      analyses, conference abstracts, and key journals were also searched. We used
      pairwise meta-analyses to estimate direct evidence from intervention-control
      trials and a network meta-analysis within a Bayesian framework to combine direct
      and indirect evidence. INCLUSION CRITERIA: Prospective randomised controlled
      trials that recruited adult patients in general intensive care units and studied
      selective digestive decontamination, selective oropharyngeal decontamination, or
      oropharyngeal chlorhexidine compared with standard care or placebo. RESULTS:
      Selective digestive decontamination had a favourable effect on mortality, with a
      direct evidence odds ratio of 0.73 (95% confidence interval 0.64 to 0.84). The
      direct evidence odds ratio for selective oropharyngeal decontamination was 0.85
      (0.74 to 0.97). Chlorhexidine was associated with increased mortality (odds ratio
      1.25, 1.05 to 1.50). When each intervention was compared with the other, both
      selective digestive decontamination and selective oropharyngeal decontamination
      were superior to chlorhexidine. The difference between selective digestive
      decontamination and selective oropharyngeal decontamination was uncertain.
      CONCLUSION: Selective digestive decontamination has a favourable effect on
      mortality in adult patients in general intensive care units. In these patients,
      the effect of selective oropharyngeal decontamination is less certain. Both
      selective digestive decontamination and selective oropharyngeal decontamination
      are superior to chlorhexidine, and there is a possibility that chlorhexidine is
      associated with increased mortality.

PMID- 24687316
TI  - Segond fracture in an adult is not pathognomonic for ACL injury.
AB  - The Segond fracture is an avulsion fracture of the lateral tibial plateau and is
      considered pathognomonic for anterior cruciate ligament (ACL) injury. A case of a
      Segond fracture occurring with a clinically, radiologically and arthroscopically
      intact ACL is presented. This was associated with a serious injury to the
      posterolateral corner requiring surgical reconstruction. Relevant literature is
      discussed, and the suggestion is made that, whilst an ACL rupture may be the most
      commonly noted soft tissue component associated with a Segond fracture, the
      clinician should have a high level of suspicion for other serious soft tissue
      injuries. Level of evidence V.

PMID- 24687318
TI  - [Securing the financing of care for the frail elderly: problems and solutions].
AB  - Projects within the Dutch National Program for Elderly Care (NPO) have been
      experimenting since 2008 to increase coherence in care for the frail elderly.
      Invest-NPO explored the problems and solutions to secure the financing of these
      innovative projects. Problems were expected with coordination because there was
      not yet a structural reimbursement for such an activity for the frail elderly.
      There where doubts about the adequacy of reimbursement for multidisciplinary
      consultation and certain structural conditions. The existing fragmentation across
      multiple domains and reimbursement rules made it difficult to achieve an
      integrated approach and creativeness in care. The principles of bundled payment
      can be helpful in problems concerning multidisciplinary consultation, structural
      conditions and coordination because joint agreements are needed. According to
      many, capitation is even a better solution if properly applied, because there are
      fewer boundaries in deciding how care is organized. Initiatives from
      entrepreneurs may represent first steps in the right direction. The findings of
      Invest-NPO may contribute to the development of further steps.

PMID- 24687317
TI  - Cytoprotective effects of 6'-O-galloylpaeoniflorin against ultraviolet B
      radiation-induced cell damage in human keratinocytes.
AB  - The cytoprotective effects of 6'-O-galloylpaeoniflorin against injury and death
      of human HaCaT keratinocytes resulting from ultraviolet B radiation were
      investigated. 6'-O-galloylpaeoniflorin exhibited the capacity to scavenge
      intracellular reactive oxygen species (ROS) generated by ultraviolet B radiation.
      6'-O-galloylpaeoniflorin also attenuated ultraviolet B-induced oxidative
      macromolecular damage to DNA, lipids, and proteins, decreasing the number of DNA
      strand breaks, the level of 8-isoprostane (a biomarker of lipid peroxidation),
      and the level of protein carbonylation. Moreover, 6'-O-galloylpaeoniflorin
      rescued HaCaT cells from ultraviolet induced cell death, by downregulating the
      mitochondrial apoptotic pathway. Taken together, these results indicate that 6'-O
      galloylpaeoniflorin has the potential to be developed as a medical agent against
      ROS-mediated skin diseases. 

PMID- 24687319
TI  - Reducing livestock effects on public lands in the western United States as the
      climate changes: a reply to Svejcar et al.
AB  - Svejcar et al. (Environ Manage, 2014) offered several perspectives regarding
      Beschta et al. (Environ Manage 51:474-491, 2013)--a publication that addressed
      the interacting ecological effects of climate change and domestic, wild, and
      feral ungulates on public lands in the western United States (US)--by largely
      focusing on three livestock grazing issues: (1) legacy versus current day
      impacts; (2) grazing as a fire reduction tool; and (3) the complexity of grazing.
      Regarding these issues, we indicate that (1) legacy effects to western ecosystems
      were indeed significant and contemporary livestock use on public lands generally
      maintains or exacerbates many of those effects; (2) livestock grazing has been a
      major factor affecting fire frequency, fire severity, and ecosystem trajectories
      in the western US for over a century; and (3) the removal or reduction of grazing
      impacts in these altered ecosystems is the most effective means of initiating
      ecological recovery. Svejcar et al. (Environ Manage, 2014) offer no evidence that
      livestock use is consistent with the timely recovery of grazing-degraded uplands,
      riparian areas, or stream systems. We thus conclude that public-land ecosystems
      can best persist or cope with a changing climate by significantly reducing
      ungulate grazing and related impacts.

PMID- 24687320
TI  - Risk tradeoffs in adaptive ecosystem management: the case of the U.S. Forest
      Service.
AB  - Natural resource planning processes on public lands in the United States are
      driven in large part by the requirements of the National Environmental Policy Act
      (NEPA), which dictates general processes for analyzing and disclosing the likely
      impacts of proposed actions. The outcomes of these processes are the result of
      multiple factors, many related to the manifold smaller incremental decisions made
      by agency personnel directing the processes. Through interviews with decision
      makers, team leaders, and team members on five NEPA processes within the U.S.
      Forest Service, this study examines those incremental decisions. Risk, in
      particular external relationship risk, emerged as a dominant lens through which
      agency personnel weigh and make process-related decisions. We discuss the
      tradeoffs associated with agency actors' emphasis on this form of risk and their
      potential implications for adaptive ecosystem management and organizational
      performance. 

PMID- 24687321
TI  - Comparison of Becton Dickinson Vacutainer rapid serum tube with the serum
      separator tube for routine chemistry and immunoassay tests.
AB  - AIMS: To shorten the clotting time and resolve the delayed clotting or no
      clotting on specimens from patients on anticoagulant therapy, Becton Dickinson
      (BD) recently developed the Vacutainer rapid serum tube (RST). The aim of this
      study was to systematically compare the new RST tube with the widely used serum
      separator tube (SST) for routine chemistry and immunoassay tests on 3 common
      analyser platforms. METHODS: Blood from 45 people (24 women and 21 men, age 21-77
      years) was collected using the SST and RST tubes in sequence. Sera from both
      tubes were separated and analysed simultaneously for 54, 50, and 10 chemistry
      and/or immunoassay tests on the Roche Modular, Abbott Architect, and Siemens
      Centaur analysers, respectively. RESULTS: The results from the RST tube were
      comparable with those from the SST tube on most analytes. Although the results
      for a few analytes showed statistically significant differences between the two
      tubes (p<0.05), the differences had no clinical significance for most assays.
      Only for parathyroid hormone on the Abbott Architect, the RST tube demonstrated
      clinical significant bias versus the SST tube (-15.3%, p<0.01). CONCLUSIONS: The
      RST tube provides acceptable performance for routine chemistry and immunoassay
      tests.

PMID- 24687322
TI  - Significance of oestrogen-related receptor gamma on biliary epithelial cells in
      the pathogenesis of primary biliary cirrhosis.
AB  - AIMS: Oestrogen has been speculated to play an important role in the pathogenesis
      of primary biliary cirrhosis (PBC), which mainly affects middle-aged and old-aged
      females because biliary epithelial cells (BECs) are known to express oestrogen
      receptors (ERs). Oestrogen-related receptors (ERRs) are constitutively active
      without oestrogen and competitively inhibit the ER-dependent effects of
      oestrogen. We clarified the effects of oestrogen and the significance of ERRs
      along with their association with the pathogenesis of cholangiopathy in PBC.
      METHODS: We investigated the expression of ERs and ERRs and the apoptosis-related
      cell kinetics in BECs using cultured human BECs and human liver specimens.
      RESULTS: Although cultured human BECs and the interlobular bile ducts in the
      liver expressed ERbeta, in cultured BECs, oestrogen treatment did not induce
      significant cell proliferation but increased the expression of a negative cell
      proliferation regulator (14-3-3sigma protein). The cultured BECs constantly
      expressed ERRalpha and ERRgamma, and oestrogen downregulated the ERRgamma
      expression. Furthermore, the ERRgamma expression was determined in the
      intrahepatic bile ducts and was stronger in the middle-aged and old-aged females,
      particularly those with PBC, than in the younger females. The ERRgamma ligand
      activated a transcription factor, SP1, and enhanced the expression of the pro
      apoptotic Bcl-2 family molecules and Bcl-2 inhibitor-induced apoptosis in
      cultured BECs. CONCLUSIONS: Although oestrogen downregulates the ERRgamma
      expression, the increased ERRgamma expression under oestrogen-deficient
      conditions increases the susceptibility to Bcl-2 family-mediated apoptosis in
      cultured human BECs of females, particularly those with PBC. Understanding the
      oestrogen-mediated cell kinetics is important for elucidating the pathogenesis of
      cholangiopathy in PBC.

PMID- 24687323
TI  - Weaving quality improvement and patient safety skills into all levels of medical
      training: an annotated bibliography.

PMID- 24687324
TI  - The phenomenology of empathy in medicine: an introduction.
AB  - This article is an introduction to a thematic section on the phenomenology of
      empathy in medicine, attempting to provide an expose of the field. It also
      provides introductions to the individual articles of the thematic section. 

PMID- 24687325
TI  - Empathy as a necessary condition of phronesis: a line of thought for medical
      ethics.
AB  - Empathy is a thing constantly asked for and stressed as a central skill and
      character trait of the good physician and nurse. To be a good doctor or a good
      nurse one needs to be empathic-one needs to be able to feel and understand the
      needs and wishes of patients in order to help them in the best possible way, in a
      medical, as well as in an ethical sense. The problem with most studies of empathy
      in medicine is that empathy is poorly defined and tends to overlap with other
      related things, such as emotional contagion, sympathy, or a caring personality in
      general. It is far from clear how empathy fits into the general picture of
      medical ethics and the framework of norms that are most often stressed there,
      such as respect for autonomy and beneficience. How are we to look upon the role
      and importance of empathy in medical ethics? Is empathy an affective and/or
      cognitive phenomenon only, or does it carry moral significance in itself as a
      skill and/or virtue? How does empathy attain moral importance for medicine? In
      this paper I will attempt to show that a comparison with the Aristotelian concept
      of phronesis makes it easier to see what empathy is and how it fits into the
      general picture of medical ethics. I will argue that empathy is a basic condition
      and source of moral knowledge by being the feeling component of phronesis, and,
      by the same power, it is also a motivation for acting in a good way. 

PMID- 24687326
TI  - Websites of note.

PMID- 24687327
TI  - Frontal midline theta reflects individual task performance in a working memory
      task.
AB  - Frontal midline (fm-)theta activity has been related to working memory (WM)
      processes, as it typically increases with WM load. The robustness of this effect,
      however, varies across studies and subjects, putting limits to its
      interpretation. We hypothesized that variation in the fm-theta effect may reflect
      individual differences in task difficulty with increasing WM load as indicated by
      behavioural responses. We further tested whether effects in the alpha range are
      robust markers of WM load. We recorded 64-channel EEG from 24 healthy adults
      while they memorized either 2 or 4 unfamiliar symbols (low vs. high WM load) in a
      modified Sternberg task. The last 2 s of the retention phase were analyzed for WM
      load-related changes in the theta (5-7 Hz) and alpha range (lower: 8-10 Hz,
      upper: 10.5-12.5 Hz). Higher WM load led to less accurate and slower responses.
      The increase of fm-theta with WM load was most pronounced at fm electrodes,
      localized to anterior cingulate regions, and correlated with the participants'
      decrease in accuracy due to higher WM load. Alpha peak frequency increased in the
      high compared to the low WM load condition, corresponding to a decrease in lower
      alpha range across all channels. The results demonstrate that previously reported
      variation in fm-theta workload effects can partly be explained by variation in
      task difficulty indexed by individual task accuracy. Moreover, the results also
      demonstrate that alpha WM load effects are prominent when separating upper and
      lower alpha. 

PMID- 24687328
TI  - Consequences of combined herbivore feeding and pathogen infection for fitness of
      Barbarea vulgaris plants.
AB  - Plants are often attacked by pathogens and insects. Their combined impact on
      plant performance and fitness depends on complicated three-way interactions and
      the plant's ability to compensate for resource losses. Here, we evaluate the
      response of Barbarea vulgaris, a wild crucifer, to combined attack by an oomycete
      Albugo sp., a plant pathogen causing white rust, and a flea beetle, Phyllotreta
      nemorum. Plants from two B. vulgaris types that differ in resistance to P.
      nemorum were exposed to Albugo and P. nemorum alone and in combination and then
      monitored for pathogen infection, herbivore damage, defence compounds,
      nutritional quality, biomass and seed production. Albugo developed infections in
      the insect-resistant plants, whereas insect-susceptible plants were scarcely
      infected. Concentrations of Albugo DNA were higher in plants also exposed to
      herbivory; similarly, flea beetle larvae caused more damage on Albugo-infected
      plants. Concentrations of saponins and glucosinolates strongly increased when the
      plants were exposed to P. nemorum and when the insect-susceptible plants were
      exposed to Albugo, and some of these compounds increased even more in the
      combined treatment. The biomass of young insect-susceptible plants was lower
      following exposure to flea beetles, and the number of leaves of both plant types
      was negatively affected by combined exposure. After flowering, however, adult
      plants produced similar numbers of viable seeds, irrespective of treatment. Our
      findings support the concept that pathogens and herbivores can affect each
      other's performance on a host plant and that the plant reacts by inducing
      specific and general defences. However, plants may be able to compensate for
      biomass loss from single and combined attacks over time.

PMID- 24687329
TI  - Invited review: GPCR structural characterization: Using fragments as building
      blocks to determine a complete structure.
AB  - The structural characterization of G protein-coupled receptors has surged since
      the development of methodologies to facilitate the crystallization of these
      highly helical, seven transmembrane, integral membrane receptors. In the past
      seven years, eighteen GPCR structures were determined by X-ray crystallography.
      The crystal structures represent a static picture of these conformationally
      flexible signal transducers. Analyses that probe their dynamics and
      conformational changes require other techniques, in particular solution state
      nuclear magnetic resonance studies. Such investigations are challenged by the
      size of GPCRs, their alpha-helical structure, which limits resonance dispersion,
      their tendencies to aggregate in micellar preparations and their conformational
      heterogeneity. For many years, groups have been studying GPCR fragments as a
      means to overcome some of these difficulties. The results of these fragment
      analyses are presented here. Review of the literature reveals that much of the
      original work depended on circular dichroism, infra-red spectroscopy and
      fluorescence approaches. High resolution structures obtained by NMR are compared,
      where applicable, to the available crystal structures. In most cases, the work
      done on fragments by biophysical analysis is validated by these comparisons. Our
      perspective on the field of GPCR fragment analysis is presented together with the
      future goals that must be considered if work with fragments is continued.

PMID- 24687330
TI  - In-depth analysis of pH-dependent mechanisms of electromechanical reshaping of
      rabbit nasal septal cartilage.
AB  - OBJECTIVES/HYPOTHESIS: Electromechanical reshaping (EMR) involves reshaping
      cartilage by mechanical deformation and delivering electric current to the area
      around the bend axis, causing local stress relaxation and permanent shape change.
      The mechanism of EMR is currently unclear, although preliminary studies suggest
      that voltage and application time are directly related to the concentration and
      diffusion of acid-base products within the treated tissue with little heat
      generation. This study aims to characterize local tissue pH changes following EMR
      and to demonstrate that local tissue pH changes are correlated with tissue damage
      and shape change. STUDY DESIGN: Ex vivo animal study involving EMR of rabbit
      nasal septal cartilage and biochemical estimation of tissue pH changes. METHODS:
      The magnitude and diffusion of acid-base chemical products in control (0V, 2
      minutes), shape change (4V, 4 minutes; 6V, 1, 2, 4 minutes; 8V, 1, 2 minutes),
      and tissue damage (8V, 4, 5 minutes; 10V, 4, 5 minutes) parameters following EMR
      are approximated by analyzing local pH changes after pH indicator application.
      RESULTS: There is a direct relationship between total charge transfer and extent
      of acid-base product diffusion (P <0.05). A "pH transition zone" is seen
      surrounding the bend apex above 8V, 2 minutes. Colorimetric analysis suggests
      that small local pH changes (10(-8) hydrogen ions) are at least partly implicated
      in clinically efficacious EMR. CONCLUSIONS: These results provide additional
      insight into the translational applications of EMR, particularly the relationship
      among pH changes, shape change, and tissue injury, and are integral in optimizing
      this promising technology for clinical use.

PMID- 24687331
TI  - Evaluation of a new high-throughput next-generation sequencing method based on a
      custom AmpliSeqTM library and ion torrent PGMTM sequencing for the rapid
      detection of genetic variations in long QT syndrome.
AB  - BACKGROUND AND OBJECTIVE: Inherited long QT syndrome (LQTS) is a cardiac
      channelopathy associated with a high risk of sudden death. The prevalence has
      been estimated at close to 1:2,000. Due to large cohorts to investigate and high
      rate of private mutations, mutational screening must be performed using an
      extremely sensitive and specific detection method. Mutational screening is
      crucial as this may have implications for therapy and management of LQTS
      patients. METHODS: Next-generation sequencing (NGS) workflow based on a custom
      AmpliSeqTM panel was designed for sequencing the five most prevalent
      cardiomyopathy-causing genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2) on Ion PGMTM
      Sequencer. A cohort of 30 previously studied patients was screened to evaluate
      this strategy in terms of sensitivity, specificity, practicability, and cost. In
      silico analysis was performed using NextGENe((r)) software. RESULTS: Our
      AmpliSeqTM custom panel allowed us to explore 86 % of targeted sequences
      efficiently. Using adjusted alignment settings, all genetic variants (40
      substitutions, 17 indels) present in covered regions and previously detected by
      high-resolution melt (HRM)/sequencing were readily identified. Uncovered targeted
      regions, which were mainly located in KCNH2, were further analyzed by
      HRM/sequencing strategy. Complete molecular investigation was performed faster
      and cheaper than with previously used mutation detection methods. CONCLUSION:
      Finally, these results suggested that our new NGS approach based on AmpliSeqTM
      libraries and Ion PGMTM sequencing is a highly efficient, fast, and cheap high
      throughput mutation detection method that is ready to be deployed in clinical
      laboratories. This method will allow fast identification of LQTS mutations that
      will have further implications for therapeutics.

PMID- 24687332
TI  - Novel hydrazine derivatives as selective DPP-IV inhibitors: findings from virtual
      screening and validation through molecular dynamics simulations.
AB  - The present study demonstrates and validates the discovery of two novel hydrazine
      derivatives as selective dipeptidyl peptidase-IV (DPP-IV) inhibitors. Virtual
      screening (VS) of publicly available databases was performed using virtual
      screening workflow (VSW) of Schrodinger software against DPP-IV and the most
      promising hits were selected. Selectivity was further assessed by docking the
      hits against homology modeled structures of DPP8 and DPP9. Two novel hydrazine
      derivatives were selected for further studies based on their selectivity
      threshold. To assess their correct binding modes and stability of their complexes
      with enzyme, molecular dynamic (MD) simulation studies were performed against the
      DPP-IV protein and the results revealed that they had a better binding affinity
      towards DPP-IV as compared to DPP 8 and DPP 9. The binding poses were further
      validated by docking these ligands with different softwares (Glide and Gold). The
      proposed binding modes of hydrazines were found to be similar to sitagliptine and
      alogliptine. Thus, the study reveals the potential of hydrazine derivatives as
      highly selective DPP-IV inhibitors. 

PMID- 24687335
TI  - [Living medicine: the call of a almost unknown goodness].

PMID- 24687334
TI  - Nickel oxide electrode interlayer in CH3 NH3 PbI3 perovskite/PCBM planar
      heterojunction hybrid solar cells.
AB  - This study successfully demonstrates the application of inorganic p-type nickel
      oxide (NiOx ) as electrode interlayer for the fabrication of NiOx /CH3 NH3 PbI3
      perovskite/PCBM PHJ hybrid solar cells with a respectable solar-to-electrical PCE
      of 7.8%. The better energy level alignment and improved wetting of the NiOx
      electrode interlayer significantly enhance the overall photovoltaic performance. 

PMID- 24687336
TI  - Factors associated with breast symmetry after breast conserving surgery for
      cancer.
AB  - INTRODUCTION: Breast-conserving surgery (BCS) is the standard of care for
      treatment of early breast cancer. Factors associated with poor cosmetic results
      are not well described. The aim of the present study was to evaluate factors
      associated with breast asymmetry after BCS for invasive breast cancer. MATERIAL
      AND METHODS: Patients who underwent unilateral BCS for invasive breast cancer and
      completed at least six months after radiation therapy were included. After
      informed consent, patients answered a validated questionnaire for breast
      symmetry. Demographic, clinical-pathological and surgical variables were
      recorded. Bilateral breast volume was measured in office and volume difference >
      20% was considered objective asymmetry. Variables were analyzed with chi(2) test
      and significance was considered at p < 0.05. RESULTS: One-hundred and thirtythree
      patients were included. Mean patient age was 56 +/- 9 years. Most patients were
      married (78%) with educational level of high school or greater (50.8%). Mean body
      mass index (BMI) was 25 +/- 8. Twelve percent of patients underwent >= 2 surgical
      procedures. Eighty-one percent of patients had tumors > 1 cm. Twenty-two percent
      of patients had objective breast asymmetry and 27% perceived themselves with
      asymmetry. There were no significant relationship between objective and
      subjective asymmetry. The only variable significantly associated with perception
      of breast asymmetry was educational level >= high school. CONCLUSIONS: There was
      no relationship between subjective and objective breast asymmetry after BCS,
      suggesting that cosmetic results are mainly related to patient subjective
      perception. The only variable associated with subjective breast asymmetry was
      high educational level, possibly because higher cosmetic expectations in this
      group of patients.

PMID- 24687337
TI  - [Antiretroviral adherence evaluation in Mexico: 4-day adherence recall vs. the
      adherence index].
AB  - OBJECTIVE: Compare two indirect methods for measuring adherence to
      antiretrovirals (ARV) for people living with HIV (PLWHA) in Mexico. MATERIAL AND
      METHODS: Sectional study of direct interviews with patients selected from a
      representative sample of PLWHA care units in Mexico. We estimated in 2,054
      patients the adherence of four days as the measurement used traditionally in
      Mexico and the adherence index as a measurement that is reported more correlated
      with biological measurements. For the latter, use was made of all items on the
      questionnaire AIDS Clinical Group (ACTG) (adherence rate, monitoring the schedule
      and special instructions, and time since the last time you stopped taking ARV).
      In both cases, was considered adequate adhesion values >= 95%. RESULTS: The
      adherence of four days identifies 13.2% (n = 271) of patients with levels less
      than the recommended (8.3% of 56-94% and 4.9% of 0- 55%) according to the index,
      the percentage of patients with lower levels of adherence to recommended was
      45.0% (n = 924) (40.5% of 56-94%, 4.5% of 0-55%). CONCLUSIONS: The estimate of
      adherence of 4 days may be underestimating significantly the adherence problem in
      PLWHA in Mexico, according to the comparison with the calculated value.
      Considering the values reported by the index, it is necessary to strengthen
      strategies to promote adherence to treatment and that a high percentage of
      patients has levels of adherence that jeopardize the effectiveness of treatment.

PMID- 24687333
TI  - Developmental neurotoxicity - challenges in the 21st century and in vitro
      opportunities.
AB  - In recent years neurodevelopmental problems in children have increased at a rate
      that suggests lifestyle factors and chemical exposures as likely contributors.
      When environmental chemicals contribute to neurodevelopmental disorders
      developmental neurotoxicity (DNT) becomes an enormous concern. But how can it be
      tackled? Current animal test- based guidelines are prohibitively expensive, at $
      1.4 million per substance, while their predictivity for human health effects may
      be limited, and mechanistic data that would help species extrapolation are not
      available. A broader screening for substances of concern requires a reliable
      testing strategy, applicable to larger numbers of substances, and sufficiently
      predictive to warrant further testing. This review discusses the evidence for
      possible contributions of environmental chemicals to DNT, limitations of the
      current test paradigm, emerging concepts and technologies pertinent to in vitro
      DNT testing and assay evaluation, as well as the prospect of a paradigm shift
      based on 21st century technologies.

PMID- 24687338
TI  - Clinical features and treatment outcomes of pediatric acute promyelocytic
      leukemia in a Mexican pediatric hospital.
AB  - INTRODUCTION: Acute promyelocytic leukemia (APL) is a distinct type of acute
      myeloid leukemia (AML) characterized by chromosomal translocations involving the
      retinoid acid receptor alpha (RARA) gene on chromosome 17. APL is a relatively
      rare blood disease that is highly curable with current treatment strategies;
      however, patient outcomes are heterogeneous in countries with limited resources.
      Promyelocytic leukemia accounts for 20-25% of all AML cases in Latin American
      countries. MATERIAL AND METHODS: We conducted a study from July 2007 to July 2012
      and applied the IC-APL2006 protocol. This case study reports the results from
      eleven patients with AML M3 (five males and six females). In all cases, the
      diagnoses were made by aspirating bone marrow and evaluating the t(15:17) or
      t(11:17) transcript. In eight cases, the molecular biology-based diagnostics for
      the PLM-RARa transcript were positive, and they were negative in two cases. One
      patient was positive for the PLZF-RARa transcript. RESULTS: The mean WBC at the
      time of diagnosis was 10.1 x 10(9)/L, and the mean platelet count was 17.1 x
      10(9)/L. The mean percentage of abnormal promyelocytes in the bone marrow
      aspirates was 68%. Of the eleven patients, four presented with disseminated
      intravascular coagulation. All of the patients began treatment with transretinoic
      acid (ATRA) (45 mg/m(2)/day), which led to 4 cases of ATRA syndrome. There were 2
      relapses, and the patient died in one case. The remaining ten patients were alive
      after the median follow-up period of 33.6 months (range from 11 to 60 months).
      CONCLUSION: The authors report on a series of cases involving pediatric patients
      with AML M3 seen at a single institution; the patients were stratified and
      treated with a standard protocol to obtain satisfactory results. Although the
      number of patients is limited, the health outcomes are relevant. To our
      knowledge, this is the first series of pediatric APL patients in Mexico who were
      treated with the IC-APL2006 protocol.

PMID- 24687339
TI  - Asymptomatic bacteriuria in preadolescent girls.
AB  - BACKGROUND: The detection of asymptomatic bacteriuria in preadolescent girls may
      be important due to its effects on subsequent pregnancies. OBJECTIVE: To describe
      the prevalence of asymptomatic bacteriuria in preadolescent girls and the value
      of the nitrite test for screening. MATERIAL AND METHODS: Cross-sectional study in
      girls aged 9 to 13 years. Bacteriuria was defined as the growth of > 100,000
      CFU/mL in 2 consecutive urine specimens. RESULTS: Three hundred and twenty seven
      girls were included. Asymptomatic bacteriuria was found in 7 girls, so the
      prevalence was 2.1% (95% CI, 1 to 4.4%). Escherichia coli was the isolated agent
      in all the cases. Focused interrogatory found history of urinary symptoms in 6
      girls. The utility values of the nitrite test were: sensitivity, 1; specificity,
      0.9; positive likelihood ratio, 10; and negative predictive value, 1.
      CONCLUSIONS: The prevalence of asymptomatic bacteriuria in preadolescent girls in
      this Mexican study is similar to the one reported internationally; it is
      reasonable to consider its early detection to avoid its effects on future
      pregnancies. Nitrite test seems to be good for screening.

PMID- 24687340
TI  - [Falls mortality trends in Mexico, 1979-2010].
AB  - AIM: To analyze the mortality trend by accidental falls in Mexico, from 1979 to
      2010. MATERIAL AND METHODS: We used official mortality data in Mexico. Variables
      included were mortality cause, place of lesion, age, sex, year of mortality
      registration, size of the town of occurrence, state, occupation, workplace falls.
      RESULTS: During that period, 124,509 deaths by accidental and intentional falls
      were registered; of these 77.03% were men. From 1989 (3.20 per 100,000) to 2010
      (1.99 per 100,000), the mortality trend was falling (beta = -0.053/ 100,000, p <=
      0.001). In the majority of states, we found a decreased between 1993-1997 and
      2006 to 2010, except in Aguascalientes, Puebla, Baja California Sur, Durango and
      Nuevo Leon. CONCLUSIONS: This is the first study in Mexico that showed the
      descending trend of mortality in accidental falls in the last two decades.

PMID- 24687341
TI  - [Incidence of acute rejection in patients with renal graft dysfunction].
AB  - INTRODUCTION: Acute rejection has been identified as the main cause of renal
      graft dysfunction during the first year after transplantation; it is associated
      with chronic structural and functional damage, which causes loss of graft and
      decrease in patient survival. MATERIAL AND METHODS: We performed a retrospective
      and descriptive research consisting in a review of the final reports of biopsies
      performed due to renal graft dysfunction during the postransplant period.
      Patients included were transplanted at the Instituto Nacional de Ciencias Medicas
      y Nutricion Salvador Zubiran (INCMNSZ) from January 2007 to December 2011.
      RESULTS: A total number of 223 patients underwent renal transplantation during
      the period considered for this study purpose, 222 biopsies were performed due to
      renal graft dysfunction in 118 patients (52.9%). 74.5% of patients developed
      graft dysfunction in the first year after transplantation. The main
      histopathological findings reported were immunologic events in both living donor
      (LDRTR) and deceased donor renal transplant recipients (DDRTR), borderline
      changes were the most common diagnosis. The median time to detect immune events
      as cause of dysfunction was shorter for DDRTR and they tend to occur in the first
      4 months after transplantation. CONCLUSION: We observed an incidence of 11.8% for
      acute rejection in the first year after transplantation for LDRTR and 17.4% for
      DDRTR. Further studies are needed to determine the causes of immunological events
      and their implications in the evolution of renal graft and patient's survival.

PMID- 24687342
TI  - [Performance analysis of scientific researchers in biomedicine].
AB  - BACKGROUND: There is no data about the performance of scientific researchers in
      biomedicine in our environment that can be use by individual subjects to compare
      their execution with their pairs. MATERIAL AND METHODS: Using the Scopus browser
      the following data from 115 scientific researchers in biomedicine were obtained:
      actual institution, number of articles published, place on each article within
      the author list as first, last or unique author, total number of citations,
      percentage of citations due to the most cited paper, and h-index. Results were
      analyzed with descriptive statistics and simple lineal regressions. RESULTS: Most
      of scientific researches in the sample are from the National Institutes of the
      Health Ministry or some of the research institutes or faculties at the
      Universidad Nacional Autonoma de Mexico. Total number of publications was < 50 in
      26%, from 50 to 100 in 36.5%, from 101 to 150 in 18.2%, from 151 to 200 in 9.5%,
      and more than 200 papers in 9.5%. The researcher was considered to be the main
      author, by being the first, the last or the unique author, from the 22 to 91% of
      the papers, with 75% being main author in more than 50% of the manuscripts. Total
      citations varied from 240 to 10,866. There is a significant correlation between
      the number of papers and citations, with R2 of 0.46. In the most cited paper, the
      researchers were considered the main author in 43%. The h-index varied from 7 to
      57. Eight researchers had h-index of less than 10. Most are between 11 and 20,
      25% are between 21 and 0 and only 10.4% had an h-index of more than 30. There is
      a significant correlation between number of published papers and h-index, with R2
      of 0.57. CONCLUSIONS: This work provides an analysis of scientific publications
      in a sample of 115 scientific researchers in biomedicine in Mexico City, which
      can be used to compare the productivity of individual subjects with their pairs.

PMID- 24687343
TI  - [Desynchronization/synchronization of lateral EEG rhythms during habituation to
      photostimulation in adults].
AB  - BACKGROUND: Berger related the EEG with cognition; we are attempting to identify
      which rhythms and circuits participate in habituation, a learning that decreases
      responses to meaningless stimuli which, changed the absolute power (AP) of EEG
      oscillations. OBJECTIVE: To characterize habituation, analyzing the AP of four
      rhythms in lateral regions of both hemispheres (BH), proposing that their
      diminution, desynchronization (D), means activation whereas their increase,
      synchronization (S), means inhibition. MATERIAL AND METHODS: qEEG analysis in 83
      college students, in waking state with closed eyes, and photostimulated (RPh).
      The used UAMI/Yanez software identifies RPh signals and takes 2-s samples before
      (Pre) and during RPh; the Welch periodogram integrates the AP of the four
      rhythms. We calculated the average AP (AAP) in Pre and RPh per frequency in
      bipolar lateral leads per hemisphere. AAP differences were evaluated with the
      Wilcoxon tests correcting with Bonferroni for repeated samples. Applying the
      linear regression model, we plotted the AAP distribution slopes during Pre and
      RPh. RESULTS: We established the differences of the AP of the four rhythms within
      each hemisphere and between both hemispheres (BH). During PRE, AAP of delta and
      theta increased whereas alpha and beta decreased. RPh increased the AAP (p =
      0.01) of the four rhythms in fronto-frontal (FF) leads; the increase in delta
      persisted in fronto-temporal (FT) and temporo-occipital (TO), whereas beta's
      increase persisted in all leads. The AAP of alpha decreased with the first RPh
      (D) increasing with the following ones; its slope starts with desynchronization
      and ends with synchronization. Theta followed a D/S pattern in temporal leads.
      Beta followed and ascending (S) slope in all leads. CONCLUSIONS: Habituation
      results from the D/S of a in all cortical regions, of theta in temporal, of delta
      in frontal regions and beta in all regions. Synchronization reflects
      hyperpolarization of neuronal membranes, decreasing their activity.

PMID- 24687344
TI  - MDR1 (ABCB1) polymorphisms: functional effects and clinical implications.
AB  - MDR1 gene encodes for P glycoprotein (P-gp), which plays an important role in
      bioavailability and cell-toxicity limitation of a wide range of drugs and
      xenobiotics. Three single nucleotide polymorphisms (SNPs) in the coding region
      (C3435T, C1236T and G2677T/A) are the most widely studied SNPs in MDR1 and have
      been related to substrate and inhibitor-dependent functional modifications in in
      vitro studies and reduced expression in tissues. The three SNPs exhibit the
      highest frequencies in Asian and Caucasians populations and the lowest in African
      populations. In regard to the clinical implications of MDR1 SNPs, it was found in
      large meta-analysis that C3435T SNP was associated with a slight increase in the
      susceptibility to ulcerative colitis and cancer and was related with slight
      modifications in tacrolimus pharmacokinetics and platinum-based chemotherapy
      response in lung cancer. On the other hand, C3435T SNP has shown controversial
      results in many other cases of disease susceptibility and drug pharmacokinetics
      where no meta-analyses have been performed. There is less information about
      C1236T and G2677T/A SNPs, which, although investigated in some diseases and drug
      pharmacokinetics, have a very limited number of published meta-analyses. Further
      studies should include analysis of the haplotype 1236T-2677T/A-3435T as well as
      other SNPs in MDR1, other transporters and drug metabolizers that may be related
      with the outcome variable. 

PMID- 24687345
TI  - [Interstitial lung disease (ILD) in rheumatoid arthritis (RA)].

PMID- 24687346
TI  - [Answer to the letter: interstitial lung disease (ILD) in rheumatoid arthritis
      (RA)].

PMID- 24687347
TI  - [From mentors and pillars].

PMID- 24687349
TI  - Vocational challenges in congenital heart disease.

PMID- 24687348
TI  - Cowden syndrome: mucocutaneous lesions as precursors of internal malignancy.
AB  - BACKGROUND: Cowden syndrome is an autosomal-dominant hereditary cancer syndrome
      with high variability and susceptibility. It is characterized by multiple
      hamartomas and neoplasms of ectodermal, endodermal and mesodermal origin
      affecting many organs and also by the increased risk of development of internal
      malignancies. CASE REPORT: A 62-year-old woman was referred to our Maxillofacial
      Unit with a hamartomatous mass of the left lateral tongue which had slowly grown
      and was obstructing normal speech and restricting oral intake. The patient had a
      known history of Cowden syndrome and underwent excision of the lesion under
      general anaesthetic. DISCUSSION: Orofacial mucocutaneous features are very common
      in multiple hamartoma and neoplasia syndrome with almost up to 90% of the
      patients being affected. These cutaneous and mucosal lesions, which are
      predominantly benign, often manifest prior to the development of the internal
      malignant tumours associated with the syndrome. CONCLUSIONS: The prompt
      identification of Cowden syndrome's plethoric signs and symptoms can lead to
      appropriate surveillance and multidisciplinary management. Oral manifestations
      are frequent, prominent and usually precede the establishment of malignant
      tumours of visceral organs; hence, the maxillofacial surgeon or general dentist
      may have a significant role in the recognition of the disease. Overall prognosis
      is dependent on prevention or early treatment of internal malignancies;
      consequently, early diagnosis together with frequent follow-up forms the
      cornerstone of management.

PMID- 24687350
TI  - Crystal structure of the nucleotide-binding domain of mortalin, the mitochondrial
      Hsp70 chaperone.
AB  - Mortalin, a member of the Hsp70-family of molecular chaperones, functions in a
      variety of processes including mitochondrial protein import and quality control,
      Fe-S cluster protein biogenesis, mitochondrial homeostasis, and regulation of
      p53. Mortalin is implicated in regulation of apoptosis, cell stress response,
      neurodegeneration, and cancer and is a target of the antitumor compound MKT-077.
      Like other Hsp70-family members, Mortalin consists of a nucleotide-binding domain
      (NBD) and a substrate-binding domain. We determined the crystal structure of the
      NBD of human Mortalin at 2.8 A resolution. Although the Mortalin nucleotide
      binding pocket is highly conserved relative to other Hsp70 family members, we
      find that its nucleotide affinity is weaker than that of Hsc70. A Parkinson's
      disease-associated mutation is located on the Mortalin-NBD surface and may
      contribute to Mortalin aggregation. We present structure-based models for how the
      Mortalin-NBD may interact with the nucleotide exchange factor GrpEL1, with p53,
      and with MKT-077. Our structure may contribute to the understanding of disease
      associated Mortalin mutations and to improved Mortalin-targeting antitumor
      compounds. 

PMID- 24687352
TI  - [Living medicine: shortage of resources].

PMID- 24687351
TI  - Anaplastic thyroid carcinomas incidentally found on postoperative pathological
      examination.
AB  - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is occasionally found on
      postoperative pathological examination of patients with differentiated thyroid
      carcinoma (DTC). There is no general consensus on how we should treat these
      incidentally diagnosed ATC (incidental ATC). MATERIALS AND METHODS: A total of
      675 patients with ATC were registered with the ATC Research Consortium of Japan.
      These patients were treated between 1995 and 2008 in 38 registered institutions.
      About 81 % of the ATC patients had common-type ATC and about 14 % had ATC co
      existing with a metastatic DTC lesion. The remaining 5 % had incidental ATC.
      Among the patients with incidental ATC, we investigated 25 patients whose
      clinical data were fully available. We examined the clinical profile of
      incidental ATC, and the relationships between treatment and outcome in patients
      with incidental ATC. RESULTS: The tumor size was clearly smaller, and patients
      with extrathyroid invasion or distant metastasis were significantly fewer in
      incidental ATC than in common-type ATC. Most incidental ATC coexisted with
      papillary carcinoma. While the clinical course of incidental ATC was favorable
      compared with common-type ATC, half of the patients had disease-related deaths.
      The prognostic factors of incidental ATC were nearly the same as those of common
      type ATC, but the tumor size alone was an independent factor on multivariate
      analysis. Regarding treatments, the outcome was more favorable in those who
      underwent curative resection, and the clinical course showed a slight improvement
      by the addition of external beam radiotherapy and/or chemotherapy after curative
      resection, but it did not reach statistical significance. CONCLUSION: Incidental
      ATC is the only curable type of ATC, and further studies are needed to establish
      the effectiveness of additional postoperative radiotherapy and/or chemotherapy in
      incidental ATC.

PMID- 24687353
TI  - Acute kidney injury in cardiac surgery.
AB  - INTRODUCTION: Acute kidney injury (AKI) associated with cardiac surgery is a
      common postoperative complication that increases the morbidity and mortality
      substantially. However, there is limited information of AKI after cardiac surgery
      in our institution. MATERIAL AND METHODS: We conducted a prospective,
      observational, and longitudinal analysis of adult patients that underwent to
      cardiac surgery requiring cardiopulmonary bypass and aortic cross clamp. Patients
      with preoperative chronic renal insufficiency that were on dialysis, with AKI
      detected up to 24 h before the procedure, or that received contrast agents 72 h
      before surgery were excluded. AKI was defined by the AKIN classification.
      Patients were followed up to 7 days after surgery or before if discharged from
      the intensive care unit. We analyzed age, sex, body mass index (BMI), co
      morbilities, previous cardiac surgery, left ventricular ejection fraction, New
      York Heart Association class, type of procedure, cardiopulmonary bypass time,
      cross clamp time and bleeding. RESULTS: Our analysis included 164 patients
      submitted to cardiac surgery. In the follow up, 84% did not have AKI, 11% had
      AKIN 1 and 2 accompanied by increase in serum creatinine and 6% had AKIN 3.
      Patients with AKI were older, had a higher preoperative creatinine, plasma
      glucose level, and a lower left ventricular ejection fraction. All together
      patients with AKIN had a longer hospital stay and a higher mortality (p < 0.001).
      The preoperative use of insulin was associated with the development of AKI, and
      there was a higher number of patients with a New York Heart Association class III
      and IV for heart failure in the more sever forms of AKI (p = 0.01). The logistic
      regression analysis revealed that patients with a high preoperative blood urea
      nitrogen (> 20 mg/dL) creatinine level (> 1 mg/dL), uric acid (> 7 mg/dL) and
      lower albumin (< 4 g/dL) or lower intraoperative hemoglobin (< 8 g/dL) had a
      higher risk for postoperative AKI. CONCLUSIONS: The prevalence of AKI in our
      Institute is of 17%. Patients with AKIN 2 and 3 had a higher mortality and a
      longer stay in the intensive care unit. The major risk factors for AKI
      development were identified.

PMID- 24687354
TI  - [Pediatric cardiovascular surgical data base registry in Mexico. First report].
AB  - INTRODUCTION: Current world tendency is the detection of health problems in order
      to offer solution alternatives by means of the development of computarized data
      bases. OBJECTIVE: To present the results of a computerized data base developed
      for the registry of pediatric cardiac surgery with the support of Asociacion
      Mexicana de Especialistas en Cardiopatias Congenitas (AMECC, A.C.). MATERIAL AND
      METHODS: A one-year analysis (from August 1, 2011 to July 31, 2012) of a
      computerized data base was performed with the support of AMECC and the
      participation of the most important Mexican institutions for pediatric surgical
      heart disease health care, particularly for the uninsured population. RESULTS:
      There were 7 health institutions voluntarily incorporated to the national data
      base registry, and in the first year of observation, 943 surgical procedures in
      880 patients and 7% re-operations (n = 63), were reported. Patients up to one
      year old accounted for 38%. The most frequent types of operated congenital heart
      diseases were: patent ductus arteriosus (n = 96), ventricular septal defect (n =
      86), tetralogy of Fallot (n = 72), atrial septal defect (n = 68), and aortic
      coarctation (n = 54). Elective procedures were 90%, and 62% of them were
      performed with the use of cardiopulmonary bypass. Overall mortality was 7.5% with
      the following RACHS-1 score risk distribution: 1 (n = 4.2%), 2 (n = 19.6%), 3 (n
      = 22.8%), 4 (n = 12.19%), 5 (n = 1.25%), 6 (n = 6.44%) and not classifiable (n =
      2.9%). CONCLUSIONS: Although this analysis gives a representative vision of the
      cardiovascular surgical health care for the uninsured national pediatric
      population, the incorporation of other health institutions to this data base may
      lead us to have a most realistic overview in relation to the surgical
      cardiovascular health care for the up to 18 year-old population.

PMID- 24687355
TI  - Safety of a dual potential prebiotic system from Mexican agave "Metlin(r) and
      Metlos(r)", incorporated to an infant formula for term newborn babies: a
      randomized controlled trial.
AB  - RATIONALE: Infant formulae are being supplemented with probiotics, prebiotics, or
      symbiotic despite uncertainties regarding their efficacy. Mexican agave is an
      interesting source of fructans with particular features and with potential
      prebiotic effects. MATERIAL AND METHODS: RCT in 600 healthy term babies (20 +/- 7
      days), allocated to receive standard infant formula (control) or infant formula
      added with a dual prebiotic system "Metlin(r) and Metlos(r)", from Mexican agave.
      Primary outcomes include stools frequency, stools consistency, gastrointestinal
      intolerance (frequency of abdominal distension, flatulency, regurgitations,
      vomiting). Secondary outcomes include changes on weight and height along the
      study and frequency of dermatologic problems (eczema). RESULTS: In 66,120 days of
      total follow-up, there were no differences on the frequency of stools passage
      (Human Milk: 3.8 +/- 2.4 evacuations per day; Pro + Metlin + Metlos 3.6 +/- 2.0;
      Pro + Metlin 3.6 +/- 2; only Pro 3.4 +/- 2.3  only formula 3.4 +/- 2.0; p NS).
      Consistency of stools was similar between human milk and prebiotics supplemented
      groups. Also the frequency of gastrointestinal symptoms was significantly low
      between these groups. CONCLUSIONS: Fructans derivate from agave and added to
      infant formula are safe and well tolerated by Mexican healthy term babies.

PMID- 24687356
TI  - [Genotype-phenotype correlation in a sample of Mexican patients with cystic
      fibrosis].
AB  - INTRODUCTION: Cystic fibrosis is a lethal autosomal recessive disease, commonly
      seen in Caucasian population. The World Health Organization (WHO) estimated that
      in Mexico, the incidence is approximately 1 per 8,500 live births. Defects in
      CFTR (cystic fibrosis transmembrane conductance regulator) protein are
      responsible for alterations in the transport of chloride in the apical membrane
      of exocrine epithelial cells. This results to a lot of variability in the
      clinical manifestations, which range from a very serious disease that compromises
      the life of the patient, to only primary infertility due to absence of CBAVD. The
      study of the CFTR gene, responsible for this entity, has led to understand the
      correlation between the molecular defects in this gene and the clinical
      expression of the patients. Most reports show that only pancreatic function in CF
      patients directly correlated with genotype and not with other clinical features
      such as lung disease. OBJECTIVE: In this work we analyzed the genotype-phenotype
      correlation in a cohort of Mexican patients with CF. MATERIAL AND METHODS: We
      included 230 patients with CF, stratified based on the genotype and pancreatic
      disease. Both ratings were correlated with clinical parameters as in sweat
      chloride levels, lung disease, pancreatic insufficiency or sufficiency (IP and
      SP) and colonization by Pseudomonas aeruginosa (P. aeruginosa). RESULTS AND
      DISCUSSION: Our data suggest a strong correlation between the severity of
      mutations and pancreatic function. Related to this, significant differences were
      observed in sweat chloride levels, lung disease, colonization by P. aeruginosa,
      and the age of onset of symptoms, and diagnosis among patients with IP and SP (p
      < 0.001). The close correlation between IP, both with mutations that eliminate
      the function of CFTR gene, as with the presence of more serious clinical picture,
      suggests that IP could be used as an indicator of the severity of CF patients
      especially in those without characterized mutations yet.

PMID- 24687357
TI  - [Life styles associated cognitive impairment. Study from the community pharmacy].
AB  - OBJECTIVE: Frequency of cognitive impairment among people over 65 years old in
      community pharmacy. Study of asssociated factors, referral of cases to the
      specialist and inclusion in a program of health education. MATERIAL AND METHODS:
      Cross-sectional study of prevalence, frequency, conducted in four pharmacies (two
      urban and two rural pharmacies) in the Autonomous Community of Valencia.
      PARTICIPANTS: people over 65 years old who come to the pharmacy and who agree to
      participate in the study after signing an informed consent. It is used as the
      initial screening test, the Short Portable Mental State Questionnaire of
      Pfeiffer. Pfeiffer positive cases undergo a second test (Mini-Mental State
      Examination, NORMACODEM version). A questionnaire designed specifically for the
      study has been used to collect information. It includes questions to gain
      demographic data, questions on lifestyle and chronic diseases. We used analysis
      logistic regression multilevel. RESULTS: 245 patients have participated (76% of
      respondents). 12.65% were detected to have cognitive impairment. In the Logistic
      regression analysis multivariate there is a relation between cognitive impairment
      and some variables: age, lack of reading habit, unusual reading habit, sleeping
      less than 6 or more than 8 hours a day. Only 12.9% wanted to be referred for
      clinical evaluation and 42% were included in a cognitive training program.
      CONCLUSIONS: There are asssociation between lifestyle habits that are modifiable
      and cognitive impairment.

PMID- 24687358
TI  - [Burnout syndrome in elderly care takers working in social care homes].
AB  - OBJECTIVE: To identify the presence and characteristics of Burnout syndrome in
      subjects dedicated to the care of older adults in homes for seniors. MATERIAL AND
      METHODS: A descriptive study was done, 46 workers of 10 homes in Merida, Yucatan,
      were included. Subjects older than 18 years and who have direct interaction with
      adults were included. To evaluate the presence of Burnout syndrome the Spanish
      version of the Maslach Burnout Inventory was used. RESULTS: Sixty-five percent of
      the population studied was female and 35% male, the average age was 38 years,
      with a range of 19-60 years. 87% of the studied population had some level of
      Burnout syndrome. In 60% of homes all the workers were affected. Regard gender
      90% of the women has some grade of Burnout syndrome and 81% of males. Respect
      areas affected, 30% had emotional exhaustion, 46% depersonalization and 95% lack
      of realization. According the number of affected areas 45% were affected in one
      area, 30% in two and 25% in three, the latter representing 22% of the study
      population. CONCLUSIONS: There is a high frequency of Burnout syndrome among
      subjects who are dedicated to caring for the elderly. Personal accomplishment was
      the most affected area. Subjects with lowest salary present higher frequency of
      Burnout syndrome.

PMID- 24687359
TI  - [Glycosylation of antibodies and their pathogenic effect].
AB  - Immunoglobulin G (IgG) has covalently linked a sugar chain in the crystallizable
      fragment (Fc). This structure consists of double stranded glycosidic complexes
      with a high degree of heterogeneity that contribute to define the affinity to
      their specific receptors, and partly determine their biological activity.
      Recently was identified an anti-inflammatory mechanism mediated by IgG based on
      their different alternatives of Fc glycosylation and their interaction with the
      specific adhesion receptor of dendritic cells (DC-SIGN). This mechanism has
      clinical and therapeutic implications in autoimmune diseases. The objective of
      this review is to describe the biochemical structure of sugars associated to the
      Fc of IgG and its variants in relation to specific functions and pathogenicity,
      particularly in tuberculosis, in which may also have therapeutic implication. 

PMID- 24687360
TI  - [The Bernardino Alvarez Farm Hospital and Farm School: antecedents to Instituto
      Nacional de Neurologia y Neurocirugia].
AB  - By 1960, Mexico's Manicomio General (General Asylum) could no longer fulfill the
      functions for which it was created so implementation of the so-called Castaneda
      Operation began, an initiative designed to close down and relocate psychiatric
      patients to other institutions. At that time, Dr. Manuel Velasco-Suarez was in
      charge of the General Direction of Neurology, Mental Health and Rehabilitation,
      and planned to create the Institute of Neurology on a site he already possessed
      for its construction. The Asylum was a dependency of the aforementioned Direction
      and Velasco- Suarez decided that some patients at the Castaneda could be moved to
      the old hacienda house that stood on that terrain. Thus was born the Bernardino
      Alvarez Farm Hospital. A year later, in 1961, the Farm School for the Weak
      Minded, also named Bernardino Alvarez was established there as well. This paper
      examines the history of these two institutions as antecedents to the Instituto
      Nacional de Neurologia y Neurocirugia. 

PMID- 24687361
TI  - [In memoriam. Dr. Hector Orozco Zepeda].

PMID- 24687362
TI  - [National guidelines of non-Hodgkin lymphoma].

PMID- 24687363
TI  - [Answer to the letter: National guidelines of non-Hodgkin lymphoma].

PMID- 24687365
TI  - Dyspareunia and pelvic floor muscle function before and during pregnancy and
      after childbirth.
AB  - INTRODUCTION AND HYPOTHESIS: There is limited knowledge on dyspareunia during
      pregnancy and postpartum and the role of the pelvic floor muscles (PFM) in women
      with dyspareunia. Aims of the study were to investigate the presence of
      dyspareunia before and during pregnancy and postpartum, and to compare vaginal
      resting pressure (VRP), PFM strength, and endurance between women with and those
      without dyspareunia. It was hypothesized that there is no difference in PFM
      variables between women with and those without dyspareunia. METHODS: Three
      hundred nulliparous women participated in this prospective cohort and answered
      questions about dyspareunia and the level of bother at gestational weeks 22 and
      37, 6 and 12 months postpartum, and retrospectively prior to their pregnancies
      using ICIQ-FLUTSsex. PFM variables were assessed by manometer at gestational week
      22, and 6 and 12 months postpartum. Comparisons between groups were analyzed
      using independent samples t test. RESULTS: Twenty-eight and 30 % of the women
      reported dyspareunia at pre-pregnancy and at gestational week 22 respectively. At
      gestational week 37, and 6 and 12 months postpartum, the percentages were 40, 45,
      and 33 respectively. No difference in PFM variables was found between women with
      and those without dyspareunia. Level of bother was higher postpartum than before
      and during pregnancy. CONCLUSIONS: Symptoms of dyspareunia were common at all
      time points. No link could be made between PFM function and dyspareunia. Women
      suffering from dyspareunia postpartum reported it as being bothersome. Our
      findings suggest that women should be asked about symptoms of dyspareunia related
      to pregnancy, and that future research should aim for preventative and
      therapeutic strategies.

PMID- 24687366
TI  - Effect of vaginal delivery on the external anal sphincter muscle innervation
      pattern evaluated by multichannel surface EMG: results of the multicentre study
      TASI-2.
AB  - INTRODUCTION AND HYPOTHESIS: A correlation exists between external anal sphincter
      (EAS) damage during birth and the subsequent development of fecal incontinence.
      This study evaluated the effect of delivery-related trauma on EAS innervation by
      means of intra-anal EMG performed with a rectal probe with 16 silver electrodes
      equally spaced along the circumference, before and after delivery. METHODS: Pre
      partum EMG measurements were performed on 511 women, by nine clinical partners
      from five European countries at the 28th to 34th gestational weeks and the 6th to
      8th post-delivery weeks; 331 women returned, after delivery, for the second test.
      The innervation zones (IZ) of EAS single motor units were identified by means of
      an EMG decomposition algorithm. RESULTS: The subjects were divided into four
      groups according to the delivery mode (Caesarean, vaginal with no evident damage,
      spontaneous lacerations and episiotomies). The number of IZs before and after
      delivery was compared. In the 82 women who underwent right mediolateral
      episiotomy, a statistically significant reduction of IZs was observed, after
      delivery, in the right ventral quadrant of the EAS (side of the episiotomy).
      Women who had Caesarean section, spontaneous lacerations or lack of evident
      damage did not present any significant change in the innervation pattern.
      CONCLUSIONS: Right episiotomy reduces the number of IZs on the right-ventral side
      of the EAS. The fast and reliable test proposed indicates the sphincter
      innervation pattern before delivery and helps obstetricians to evaluate the risks
      and to choose the preferred side of the episiotomy, if deemed necessary at the
      time of delivery.

PMID- 24687367
TI  - Clinical usefulness of the PAXgeneTM bone marrow RNA system for stabilizing total
      RNA.
AB  - The collection of clinical samples, such as bone marrow (BM) and peripheral
      blood, is an important procedure for the extraction of the cellular RNA. It is
      essential to preserve the extracted RNA during and after the collection of
      clinical samples to ensure the accurate analysis of gene expression. To date, the
      PAXgeneTM Blood RNA System has been proven useful for stabilizing RNA extracted
      from peripheral blood; however, a problem concerning the stability of the total
      RNA stored using the system has been identified. The PAXgeneTM Bone Marrow RNA
      System (BM system) is a newly developed system, and its clinical usefulness as a
      stabilizer for the cellular RNA in BM and peripheral blood was investigated with
      respect to the quality of RNA extracted using this system. A quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) was carried out using total RNA
      extracted with the BM system, which showed that total RNA was more stable in the
      BM system than in the conventional system, indicating that the BM system can be
      applied to RT-PCR. The BM system enabled us to detect Wilms' tumor suppressor
      gene (WT1) more effectively than the conventional system. In conclusion, the BM
      system is clinically valuable for extracting and stabilizing total RNA of high
      quality.

PMID- 24687368
TI  - "I don't need my patients' opinion to withdraw treatment": patient preferences at
      the end-of-life and physician attitudes towards advance directives in England and
      France.
AB  - This paper presents the results of a qualitative interview study exploring
      English and French physicians' moral perspectives and attitudes towards end-of
      life decisions when patients lack capacity to make decisions for themselves. The
      paper aims to examine the importance physicians from different contexts accord to
      patient preferences and to explore the (potential) role of advance directives
      (ADs) in each context. The interviews focus on (1) problems that emerge when
      deciding to withdraw/-hold life-sustaining treatment from both conscious and
      unconscious patients; (2) decision-making procedures and the participation of
      proxies/relatives; (3) previous experience with ADs and views on their
      usefulness; and (4) perspectives on ways in which the decision-making processes
      in question might be improved. The analysis reveals differences in the way
      patient preferences are taken into consideration and shows how these differences
      influence the reasons physicians in each country invoke to justify their
      reluctance to adhering to ADs. Identifying cultural differences that complicate
      efforts to develop the practical implementation of ADs can help to inform
      national policies governing ADs and to better adapt them to practice. 

PMID- 24687369
TI  - Triatominae biochemistry goes to school: evaluation of a novel tool for teaching
      basic biochemical concepts of Chagas disease vectors.
AB  - We evaluate a new approach to teaching the basic biochemistry mechanisms that
      regulate the biology of Triatominae, major vectors of Trypanosoma cruzi, the
      causative agent of Chagas disease. We have designed and used a comic book,
      "Carlos Chagas: 100 years after a hero's discovery" containing scientific
      information obtained by seven distinguished contemporary Brazilian researchers
      working with Triatominaes. Students (22) in the seventh grade of a public
      elementary school received the comic book. The study was then followed up by the
      use of Concept Maps elaborated by the students. Six Concept Maps elaborated by
      the students before the introduction of the comic book received an average score
      of 7. Scores rose to an average of 45 after the introduction of the comic book.
      This result suggests that a more attractive content can greatly improve the
      knowledge and conceptual understanding among students not previously exposed to
      insect biochemistry. In conclusion, this study illustrates an alternative to
      current strategies of teaching about the transmission of neglected diseases. It
      also promotes the diffusion of the scientific knowledge produced by Brazilian
      researchers that may stimulate students to choose a scientific career.

PMID- 24687370
TI  - Circadian clocks and inflammation: reciprocal regulation and shared mediators.
AB  - The immune system is deeply interconnected with the endogenous 24-h oscillators
      of the circadian system. Indeed, the connection between these two physiological
      systems occurs at multiple levels and in both directions. On one hand, various
      aspects of the immune system show daily rhythms, which appear to be essential for
      healthy immune maintenance and proper immune response. On the other hand, immune
      responses cause changes in circadian rhythms, disrupting their delicate balance
      and manifesting in disease. Indeed, immune challenges cause various time-, gene-,
      and tissue-specific effects on circadian-regulated factors. This article reviews
      the possible mediators of the cross talk between the circadian clock and the
      immune system, in particular the inflammatory pathways. The rhythmic expression
      of cytokines and their receptors, as well as other rhythmically regulated humoral
      factors such as glucocorticoids, melatonin, leptin, or prostaglandins, could gate
      the effects of the immune response on the circadian system. In addition, systemic
      cues such as body temperature and neuronal connections between the brain and
      peripheral tissues may underlie the immune-circadian communication. 

PMID- 24687371
TI  - A computational approach predicting CYP450 metabolism and estrogenic activity of
      an endocrine disrupting compound (PCB-30).
AB  - Endocrine disrupting chemicals influence growth and development through
      interactions with the hormone system, often through binding to hormone receptors
      such as the estrogen receptor. Computational methods can predict endocrine
      disrupting chemical activity of unmodified compounds, but approaches predicting
      activity following metabolism are lacking. The present study uses a well-known
      environmental contaminant, PCB-30 (2,4,6-trichlorobiphenyl), as a prototype
      endocrine disrupting chemical and integrates predictive (computational) and
      experimental methods to determine its metabolic transformation by cytochrome P450
      3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) into estrogenic byproducts.
      Computational predictions suggest that hydroxylation of PCB-30 occurs at the 3-
      or 4-phenol positions and leads to metabolites that bind more strongly than the
      parent molecule to the human estrogen receptor alpha (hER-alpha). Gas
      chromatography-mass spectrometry experiments confirmed that the primary
      metabolite for CYP3A4 and CYP2D6 is 4-hydroxy-PCB-30, and the secondary
      metabolite is 3-hydroxy-PCB-30. Cell-based bioassays (bioluminescent yeast
      expressing hER-alpha) confirmed that hydroxylated metabolites are more estrogenic
      than PCB-30. These experimental results support the applied model's ability to
      predict the metabolic and estrogenic fate of PCB-30, which could be used to
      identify other endocrine disrupting chemicals involved in similar pathways.

PMID- 24687372
TI  - Being an editor of a psychiatric journal.

PMID- 24687373
TI  - Teaching empathy during clerkship and residency.

PMID- 24687374
TI  - Quality improvement (QI) education in a psychiatry residency program: "diagnosis
      and consultation" as key QI skills.

PMID- 24687375
TI  - Acquisition and retention of basic pathophysiological knowledge in psychiatry.
AB  - OBJECTIVE: An important and yet underexplored issue in medical education concerns
      the extent to which students retain early taught theoretical knowledge during
      subsequent stages of their academic schooling. This study aimed to assess the
      degree to which medical students retain basic pathophysiological knowledge on
      biological psychiatry across different stages of medical education. METHODS: A
      cross-sectional investigation was conducted using a multiple choice questionnaire
      (MCQ) of objective pathophysiological knowledge taught in a course given to
      second-year students, supplemented by questions measuring subjective interest and
      attributed importance to the content taught. Comparisons (ANOVA with post hoc
      Tukey tests) were carried out among five groups (n = 417): baseline (freshmen),
      pre-intervention group (second-year students attending the first day of the
      course), immediate tested group (second-year students on the final day of the
      course), 1-year delayed tested group (third-year students), and 3-years delayed
      tested group (interns). RESULTS: In comparison to the baseline and pre
      intervention groups, the other three groups that received teaching displayed
      significantly better levels of knowledge (p < 0.0001). Differently, scores of
      interest and attributed importance were higher in the pre-intervention group
      relative to all other groups that were tested after having been given the course
      (p < 0.005). There were no significant associations between knowledge retention,
      attributed importance, and interest within pre-intervention or post-intervention
      groups. CONCLUSIONS: The only modest loss of knowledge over time indicates that a
      large proportion of early taught content is retained throughout the later years
      of medical education. Nevertheless, retained knowledge does not seem to be
      associated with subjective interest and attributed importance to such early
      taught content.

PMID- 24687376
TI  - Effect of sleeve gastrectomy on osteopontin circulating levels and expression in
      adipose tissue and liver in rats.
AB  - BACKGROUND: Sleeve gastrectomy (SG) constitutes an effective procedure for the
      treatment of morbid obesity. The aim of the present study was to establish in
      rats the effects of surgically induced weight loss on circulating concentrations
      and mRNA expression in adipose tissue and liver of osteopontin (OPN), a
      proinflammatory protein involved in the development of obesity. METHODS: Eighty
      male diet-induced obese Wistar rats were subjected to surgical interventions
      [sham operation (SH), SG, or pair-fed to the amount of food eaten by SG animals]
      and dietary interventions [fed ad libitum with a normal chow diet (ND) or a high
      fat diet (HFD)]. Body, epididymal adipose tissue (EWAT), and liver weights were
      determined. Circulating OPN concentrations and the transcript levels of Spp1
      (OPN) in EWAT and liver were analyzed. RESULTS: Rats undergoing SG showed
      decreased body weight (P < 0.001) and fat mass (P < 0.001) and greater excess
      weight loss (P < 0.001). The HFD significantly decreased serum OPN levels (P <
      0.001). However, SG did not change serum OPN concentrations. OPN expression was
      dramatically increased in animals fed HFD (P < 0.001) in EWAT, but was unaffected
      by SG. The expression of OPN in the liver was not affected by HFD or SG.
      CONCLUSIONS: Circulating OPN levels decreased with HFD feeding remaining
      unaltered after SG. The expression of Spp1 in EWAT and liver was not modified by
      SG. The global improvement of metabolism after SG appears not to involve changes
      in serum OPN concentrations as well as in EWAT and liver expression in rats.

PMID- 24687377
TI  - MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast
      cancer metastasis.
AB  - MAGEC2 is a member of melanoma antigen (MAGE) family of cancer-testis antigens
      and associated with tumor relapse and metastasis. Here, we investigated the
      expression of MAGEC2 in patients with breast cancer and its clinical effects with
      underlying mechanisms. The expression levels of MAGEC2 were compared between 420
      invasive ductal carcinoma (IDC) and 120 ductal carcinoma in situ of the breast.
      Correlations between MAGEC2 expression and clinico-pathologic factors or survival
      of patients with IDC were analyzed. In addition, MAGEC2 expression levels in
      tumor tissues dissected from the primary focus and matched tumor-invaded axillary
      lymph nodes were analyzed in 8 breast cancer patients. The functional effects of
      MAGEC2 overexpression were assessed in vitro using scratch assay and transwell
      chamber assay. MAGEC2 expression was increased in metastatic breast cancer in
      comparison to the non-metastatic. MAGEC2 expression was significantly associated
      with ER negative expression (P = 0.037), high tumor grade (P = 0.014) and stage
      (P = 0.002), high incidence of axillary lymph node metastasis (P = 0.013), and
      distant metastasis (P = 0.004). Patients with tumor with MAGEC2 positive
      expression have a worse prognosis and a shorter metastasis free interval.
      Multivariate analyses showed that MAGEC2 expression was an independent risk
      factor for patient overall survival and metastasis-free survival. Breast cancer
      cells that overexpressed MAGEC2 had stronger migratory and invasive potential
      than control-treated cells. Epithelial markers (E-cadherin and cytokeratin) were
      down-regulated in MAGEC2-overexpressing cells compared to controls, whereas
      mesenchymal markers (vimentin and fibronectin) were upregulated. Our results
      indicate that MAGEC2 has a role in breast cancer metastasis through inducing
      epithelial-mesenchymal transition. In addition, MAGEC2 is a novel independent
      poor prognostic factor in patients with IDC. Thus, targeting MAGEC2 may provide a
      novel therapeutic strategy for breast cancer treatment.

PMID- 24687379
TI  - A relapsing macrodactyly.
AB  - Lipofibromatous hamartoma is an uncommon benign tumor, usually unknown or
      misdiagnosed. We report the case of a 61-year-old patient presenting an acquired
      painful macrodactyly of the left thumb with paresthesia in the median nerve
      territory. Clinical examination reveals a tumefaction of the volar side of the
      wrist. She had a medical history of amputation of the forefinger for macrodactyly
      without any diagnosis. Paraclinical exploration guided us to the correct
      diagnosis; hypertrophic bone structures of the affected finger were detected on
      radiographs. The left median nerve appeared hypertrophic, with a fatty
      infiltration on the ultrasound exploration. These pathological findings revealed
      a late discovered lipofibromatous hamartoma of the median nerve, a rare entity
      often associated with macrodactyly and diagnosed in childhood. Therefore, we
      retrospectively made the same diagnosis for the amputated index finger with the
      analysis of her ancient paraclinical exams. Lipofibromatous hamartoma remains an
      obscure pathology and its treatment stays controversial. 

PMID- 24687380
TI  - High expression levels of microRNA-629, microRNA-525-5p and microRNA-516a-3p in
      paediatric systemic lupus erythematosus.
AB  - Paediatric systemic lupus erythematosus (pSLE) refers to childhood-onset systemic
      lupus erythematosus. pSLE has its own unique characteristics, and its
      pathogenesis is unclear. To study the relationship between microRNAs (miRNAs) and
      pSLE, we selected three pSLE patients who were newly diagnosed and had not yet
      been treated, and two controls were also included. We collected their peripheral
      blood mononuclear cells to perform Agilent human miRNA (8*15 k) 12.0 analysis. To
      verify the results, we next selected 12 other pSLE patients who had different
      disease activities and 3 healthy controls and conducted real-time PCR. The
      results showed high expression of miRNA-516a-3p, miRNA-629 and miRNA-525-5p in
      pSLE patients with active disease; these levels were normal in patients without
      active disease. Increased expression levels of these three miRNAs were positively
      correlated with the score obtained from the systemic lupus erythematosus disease
      activity index scoring system (SLEDAI) 2000 and C-reactive protein (CRP) levels.
      Furthermore, the target genes of these three miRNAs were important to the
      pathogenesis of pSLE. Therefore, these three miRNAs might be specific to pSLE and
      may be used as novel biomarkers of pSLE to diagnose and monitor the disease.

PMID- 24687381
TI  - Associations of VEGF and VEGFR2 polymorphisms with increased risk and
      aggressiveness of multiple myeloma.
AB  - Angiogenesis has been highlighted as a critical component in the progression of
      multiple myeloma (MM), and vascular endothelial growth factor (VEGF) as well as
      its type 2 receptor (VEGFR2) are thought to play a major role in the process.
      Single nucleotide polymorphisms (SNPs) have been described in VEGF and VEGFR2
      genes, with quantitative or qualitative changes in encoded VEGF and VEGFR2. The
      roles of VEGF -2578C/A, -1154G/A, and -634G/C as well as VEGFR2 -604T/C and
      +1192G/A SNPs in the risk and manifestations of MM are still unknown; therefore,
      this study aimed to clarify this issue. DNA from 192 patients and 209 controls
      were analyzed by real-time polymerase chain reaction for identification of
      genotypes. The frequencies of VEGF -2578CC, VEGF -2578CC plus VEGF -634GG, and
      VEGF -2578CC plus VEGF -1154GG plus VEGF -634GG genotypes were higher in patients
      than in controls. Carriers of the respective genotypes had a 1.89-, a 5.52-, and
      a 4.91-fold increased risk for MM than others. VEGF -2578CC plus VEGFR2 +1192GG,
      VEGF -2578CC plus VEGF -634GG plus VEGFR2 +1192GG, and VEGF -1154GG plus VEGF 
      634GG plus VEGFR2 -604TT combined genotypes were more common in patients than in
      controls. Carriers of the respective genotypes had a 2.56-, a 10.97-, and a 14.10
      fold increased risk for MM than others. An excess of VEGFR2 -604TT genotype was
      also seen in patients with stage II or III tumors when compared with those with
      stage I tumors. Our data suggest, for the first time, that inherited
      abnormalities in VEGF and VEGFR2 pathways influence the risk and aggressiveness
      of MM.

PMID- 24687383
TI  - Determination of accuracy of polycythemia vera diagnoses and use of the JAK2V617F
      test in the diagnostic scheme.
AB  - In 2005, three independent research groups described the presence of a specific
      mutation in the JAK2 gene, JAK2V617F, in patients with a Philadelphia chromosome
      negative myeloproliferative neoplasm (MPN). The percentage of patients with the
      mutation varied according to specific disease with >98 % of polycythemia vera
      (PV) patients having the mutation. In 2008, the World Health Organization issued
      new diagnostic criteria for PV including use of the JAK2V617F test as a major
      diagnostic criterion. The goal of the present study is to determine the accuracy
      of diagnosing PV in a community practice and reporting of PV to cancer
      registries, as well as assessing the integration of molecular testing into
      diagnostic paradigms. Using Geisinger Medical Center's electronic medical records
      (EMR), patients with a PV diagnosis being seen by a hematologist/oncologist
      during 2004-2009 were identified. Records were reviewed by a single
      hematologist/oncologist to determine accuracy of the treating physician's
      diagnosis and use of the molecular test for the JAK2V617F mutation. There was a
      diagnosis of PV from the treating physicians in 121 of the 204 evaluable patients
      (59 %) and another MPN in 21 (10 %). However, we confirmed a PV diagnosis in only
      90 patients (44 %). Of the 90 confirmed PV patients, 64 were JAK2V617F-mutation
      positive while 24 were not tested. While JAK2V617F testing has made a major
      impact in facilitating the successful delineation of the type of polycythemia (PV
      versus secondary polycythemia) in patients evaluated in a large, community-based
      Hematology/Oncology practice, physician usage of other critical tests is
      inconsistent leading to errors in diagnosis. JAK2V617F mutation testing in
      combination with other diagnostic criteria may help reduce diagnostic errors. 

PMID- 24687382
TI  - Expression of cereblon protein assessed by immunohistochemicalstaining in myeloma
      cells is associated with superior response of thalidomide- and lenalidomide-based
      treatment, but not bortezomib-based treatment, in patients with multiple myeloma.
AB  - Cereblon (CRBN) is essential for the anti-myeloma (MM) activity of
      immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide. However,
      the clinical implications of CRBN in MM patients are unclear. Using
      immunohistochemical (IHC) staining on paraffin-embedded bone marrow sections, the
      expression of CRBN protein in myeloma cells (MCs) was assessed in 40
      relapsed/refractory MM (RRMM) patients who received lenalidomide/dexamethasone
      (LD) and 45 and 22 newly diagnosed MM (NDMM) patients who received
      thalidomide/dexamethasone (TD) and melphalan/bortezomib/prednisolone (MVP),
      respectively. IHC staining were scored on a scale representing the diffuseness
      and intensity of positive-staining MCs (range, 0-8) and a score >=4.5 was used
      for CRBN positivity (CRBN(+)) on a cut-point analysis of all possible scores and
      response of TD and LD. Compared to CRBN(+) NDMM patients, CRBN(-) NDMM patients
      had more international staging system (ISS) III (26 vs. 61 %, respectively; P =
      0.006). In the LD and TD cohorts, the response rate (RR) was higher in CRBN(+)
      patients than CRBN(-) patients (LD 79 vs. 33 %, respectively; P = 0.005) (TD 75
      vs. 29 %, respectively; P = 0.005); however, this trend was not observed in the
      MVP cohort. In the LD and TD cohorts, the positive and negative prediction value
      of CRBN(+) for treatment response was 79 and 67 % and 75 and 71 %, respectively.
      Multivariate analysis showed that CRBN(+) was a significant factor associated
      with superior RR for LD and TD. The data suggest that expression of CRBN protein
      in MCs assessed using the IHC is a feasible approach to predict the response of
      IMiDs in MM patients.

PMID- 24687384
TI  - Abstention, alcohol consumption, and common somatic symptoms: the Hordaland
      Health Study (HUSK).
AB  - BACKGROUND: The association between alcohol consumption and somatic symptoms is
      unclear. PURPOSE: The aim of this study was to examine the cross-sectional
      association between the whole continuum of alcohol consumption, ranging from
      abstention to high-level consumption, and the overall level of common somatic
      symptoms in a large population-based sample. METHODS: Data are from the Hordaland
      Health Study, conducted in 1997-1999 with participants aged 40-46 years (N =
      15,018). The main exposure was a categorical variable based on self-reported
      abstention and alcohol consumption, while self-reported overall level of somatic
      symptoms was the outcome. The outcome was defined by the mean overall frequency
      of 17 commonly experienced somatic symptoms. Potential confounders included
      sociodemographic information, somatic diagnoses, and health-related behaviors.
      Linear regression models were computed in the statistical analyses. RESULTS: We
      found no association between different levels of alcohol consumption and overall
      level of somatic symptoms. Abstainers reported, however, a higher overall level
      of somatic symptoms compared to those who consumed alcohol at any level, even
      after adjusting for potential confounders. Investigating the individual somatic
      symptoms, we found that the abstainers had a higher frequency of 10 of the 17
      symptoms compared to the remainder, while higher frequency was found for only 2
      somatic symptoms among the 5% with the highest alcohol consumption. CONCLUSIONS:
      We found no support for an association between alcohol consumption and overall
      level of somatic symptoms. There was, however, a small association between being
      abstinent and increased level of somatic symptoms. These findings may have
      several different explanations, and further investigation is called for.

PMID- 24687385
TI  - Effects of PTH(1-84) therapy on muscle function and quality of life in
      hypoparathyroidism: results from a randomized controlled trial.
AB  - The effects of treatment with 100 MUg parathyroid hormone (PTH) (1-84) or an
      identical placebo on muscle function and quality of life (QoL) was studied in
      hypoparathyroid patients. At baseline, we found reduced QoL but no myopathy in
      the patients. Six months of treatment did not improve QoL, and muscle strength
      decreased slightly. INTRODUCTION: A reduced quality of life (QoL) and myopathy
      that may be due to the absence of PTH have been reported in patients with
      hypoparathyroidism (hypoPT). METHODS: Sixty-two patients with chronic hypoPT were
      randomized to 6 months of treatment with either PTH(1-84) 100 MUg/d s.c. or
      placebo, given as add-on therapy to conventional treatment. Muscle function and
      postural stability were investigated using a dynamometer chair, a stadiometer
      platform, the repeated chair stands test, the timed up and go test, and
      electromyography. QoL was assessed using the 36-item Short Form Health Survey and
      the WHO-5 Well-Being Index. RESULTS: The mean age of the patients was 52 +/- 11
      years, and 85 % were females. At baseline, QoL was significantly reduced in
      comparison with norm-based scores. Compared with placebo, PTH did not improve QoL
      or muscle function. Rather, max force production decreased significantly by 30 %
      at elbow flexion in the PTH group compared with the placebo group. Moreover,
      there was a nonsignificant trend for muscle strength to decrease in the upper
      extremities and on knee extension in response to PTH. Treatment did not affect
      postural stability. Electromyography showed a slight decrease in the duration of
      motor unit potentials in the PTH group, indicating a tendency toward myopathy,
      which, however was not symptomatic. CONCLUSIONS: Overall, our data do not support
      an immediate beneficial effect of PTH replacement therapy on muscle function or
      QoL. A high frequency of hypercalcemia among our patients may have compromised
      the potential beneficial effects of reversing the state of PTH insufficiency.

PMID- 24687378
TI  - MRI breast screening in high-risk women: cancer detection and survival analysis.
AB  - Women with a genetic predisposition to breast cancer tend to develop the disease
      at a younger age with denser breasts making mammography screening less effective.
      The introduction of magnetic resonance imaging (MRI) for familial breast cancer
      screening programs in recent years was intended to improve outcomes in these
      women. We aimed to assess whether introduction of MRI surveillance improves 5-
      and 10-year survival of high-risk women and determine the accuracy of MRI breast
      cancer detection compared with mammography-only or no enhanced surveillance and
      compare size and pathology of cancers detected in women screened with MRI +
      mammography and mammography only. We used data from two prospective studies where
      asymptomatic women with a very high breast cancer risk were screened by either
      mammography alone or with MRI also compared with BRCA1/2 carriers with no
      intensive surveillance. 63 cancers were detected in women receiving MRI +
      mammography and 76 in women receiving mammography only. Sensitivity of MRI +
      mammography was 93 % with 63 % specificity. Fewer cancers detected on MRI were
      lymph node positive compared to mammography/no additional screening. There were
      no differences in 10-year survival between the MRI + mammography and mammography
      only groups, but survival was significantly higher in the MRI-screened group
      (95.3 %) compared to no intensive screening (73.7 %; p = 0.002). There were no
      deaths among the 21 BRCA2 carriers receiving MRI. There appears to be benefit
      from screening with MRI, particularly in BRCA2 carriers. Extended follow-up of
      larger numbers of high-risk women is required to assess long-term survival.

PMID- 24687386
TI  - TBS result is not affected by lumbar spine osteoarthritis.
AB  - The effect of lumbar osteoarthritis on bone density and trabecular bone score
      (TBS) was evaluated cross-sectionally and prospectively in postmenopausal women.
      Lumbar spine osteoarthritis was graded according to Kellgren and Lawrence grades.
      Lumbar osteoarthritis was found to increase lumbar spine bone density, but not
      TBS. INTRODUCTION: Lumbar osteoarthritis overestimates lumbar bone density (areal
      bone mineral density (aBMD)). A new texture parameter, the TBS, has been
      proposed. Calculation of aBMD uses grey level value, while TBS uses grey level
      variation. Therefore, our hypothesis was that TBS is not influenced by lumbar
      spine osteoarthritis. METHODS: Menopausal women participating in osteoporosis and
      ultrasound (OPUS) study were included. They had an aBMD measurement of the spine
      and hip at baseline and 6-year visit. TBS was calculated on lumbar spine dual
      energy X-ray absorptiometry (DXA) scans in an automated manner. The presence of
      lumbar osteoarthritis was evaluated on baseline radiographs using Kellgren and
      Lawrence (K&L) classification. Grades range from 0 to 4. In our study,
      osteoarthritis was defined by at least K&L grade 2. RESULTS: This study included
      1,254 menopausal women (66.7 +/- 7.1 years). Among them, 727 attended the 6-year
      follow-up visit. Patients with lumbar osteoarthritis had an aBMD higher than
      those without lumbar osteoarthritis at the lumbar spine, but not at the hip.
      However, the aBMD significantly increased in all sites with the grade of K&L. In
      contrast, spine TBS was not different between patients with and without lumbar
      osteoarthritis (p = 0.70), and it was not correlated with K&L grade. Spine TBS
      and aBMD at all sites were negatively correlated with age (p < 0.0001). Body mass
      index was correlated positively with aBMD and negatively with spine TBS (p <
      0.0001). The 6-year change of aBMD was significant in the hip and nonsignificant
      in the lumbar spine. That of TBS was significant, with a 3.3 % decrease (p <
      0.0001), independent of K&L grade (p = 0.28). CONCLUSION: In postmenopausal
      women, lumbar osteoarthritis leads to an increase in lumbar spine aBMD. In
      contrast, spine TBS is not affected by lumbar osteoarthritis.

PMID- 24687387
TI  - Strontium ranelate related Stevens-Johnson syndrome: a case report.
AB  - Strontium ranelate is a relatively new medication with good safety profile for
      the treatment of postmenopausal osteoporosis. However, severe cutaneous adverse
      drug reactions have been reported, such as drug rash with eosinophilia and
      systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal
      necrolysis (TEN). We report the case of a 70-year-old woman who developed
      multiple itching erythematous macules and plaques about 1 month after beginning
      strontium ranelate medication. The cutaneous lesions progressed over the entire
      body with severe oral and ocular mucosa involvement. Probable mild SJS was
      diagnosed, compatible with the pathology findings, and strontium ranelate was
      discontinued immediately. Systemic methylprednisolone was administered to
      suppress the overactive immune system and ameliorate cutaneous symptoms. With
      early recognition and prompt treatment, the patient's prognosis was good.

PMID- 24687388
TI  - Nonalbuminuric proteinuria as a biomarker for tubular damage in early development
      of nephropathy with type 2 diabetic patients.
AB  - AIM: The aim of this study was to evaluate the association between urinary
      nonalbumin protein (NAP) and urinary tubular markers in early diabetic
      nephropathy. METHODS: Urinary NAP was measured in 118 patients with type 2
      diabetes with estimated glomerular filtration rates (eGFR) >=60 mL/min/1.73 m2.
      Urine levels of tubular markers [kidney injury molecule (KIM)-1, neutrophil
      gelatinase-assoicated lipocalin (NGAL) and liver-type fatty acid-binding protein
      (L-FABP)] were measured by using an Enzyme-linked immunosorbent assay (ELISA).
      Patients were divided into three groups according to urinary NAP values. RESULTS:
      The urine levels of KIM-1, NGAL and L-FABP were significantly higher in the third
      tertile group than in the first tertile group (all p < 0.001). There was a
      significant positive correlation between NAP and each tubular marker (KIM-1, NGAL
      and L-FABP) in univariate analysis (all p < 0.001). Urinary NAP was positively
      correlated with all urinary tubular markers after adjustment for age, duration of
      diabetes, systolic blood pressure, eGFR, low-density lipoprotein cholesterol,
      HbA1c and albumin-to-creatinine ratio (KIM-1 r = 0.170, p < 0.001; NGAL r =
      0.142, p < 0.015 and L-FABP r = 0.262, p < 0.001). In normoalbuminuric patients
      (n = 58), urinary NAP was also significantly correlated with NGAL and L-FABP in
      multivariate regression analyses (r = 0.302, p = 0.030 and r = 0.430, p = 0.001).
      CONCLUSIONS: These findings suggest that urinary NAP reflects tubular damage in
      the early-stage type 2 diabetic nephropathy (eGFR >= 60 mL/min/1.73 m2). We
      suggest that urinary NAP could be used as a biomarker for tubular damage in
      clinical practice.

PMID- 24687389
TI  - Tractable synthesis of multipurpose screening compounds with under-represented
      molecular features for an open access screening platform.
AB  - The layout of multipurpose screening libraries must address criteria for the
      compounds such as novelty, diversity potential, innovative design, and last but
      not least synthetic tractability. While academic compound collections are often
      innovative, novel, and highly divers, synthesis of analogs or larger substance
      quantities is often hampered by complex multistep syntheses with low overall
      yields. In addition, covalently binding compounds and interaction motifs designed
      to bind metal ions were discriminated against by the paradigm that these
      interaction types must almost inevitably lead to toxic effects. We would like to
      challenge this hypothesis. The lack of such interactions could be a reason for
      frequent failure in the disclosure of hits for hitherto undruggable target
      proteins using commercially available screening collections. Thus, easily
      synthesizable screening candidates equipped to bind covalently to nucleophiles or
      to metalloenzymes by chelation are under-represented in public access screening
      libraries. Within this work, we present the synthesis and deposition of 88
      compounds with five distinct functional classes, each of which features under
      represented screening motifs, for example, metal ion complexation, reversible
      covalent binding, or halogen bonding. The collection includes acetohydrazides,
      acylhydrazones, propylene glycol ethers, 2-cyanoacetamides, and 2
      cyanoacrylamides. The rational for the synthesis of most of the compounds was
      recently published by our group and is now supplemented by additional compounds
      reported here for the first time. The public access disposition enables academic
      research groups to collectively expand the druggable space and interdisciplinary
      collaborate within the scientific field. 

PMID- 24687390
TI  - National Vascular Registry Report on surgical outcomes and implications for
      vascular centres.
AB  - BACKGROUND: The National Vascular Registry Report on Surgical Outcomes (NVSRO)
      coincided with the update of the National Health Service Standard Contract for
      Specialized Vascular Services in Adults (NHSSCSVS). The latter promises patients
      minimum standards for vascular centres. The present study aimed to determine
      whether current data support the standards proposed in the NHSSCSVS. METHODS:
      Numbers of abdominal aortic aneurysm (AAA) repairs and carotid endarterectomies
      (CEAs) performed by hospital Trust and surgeon, and their outcomes were obtained
      from the NVRSO. These were assessed against NHSSCSVS recommendations that
      included: more than 60 AAA repairs per year per Trust, over 50 CEAs per year per
      Trust and at least six vascular surgeons per Trust. RESULTS: Based on NVRSO data,
      107 hospital Trusts (92.2 per cent) would fail to meet the minimum standards
      required to achieve vascular centre status. Outcomes were poorer in these
      hospitals (overall mortality rate after AAA: 2.7 versus 1.3 per cent; P = 0.007).
      There were strong associations between number of AAA repairs or CEAs per Trust
      and better outcomes (AAA repair, P < 0.001; CEA, P = 0.004). These remained
      significant when analysed by individual surgeon (AAA repair, P < 0.001; CEA, P <
      0.001). Trusts undertaking 60 or fewer elective AAA repairs per year had
      significantly higher elective AAA mortality rates (2.7 versus 1.7 per cent; P =
      0.010). Trusts performing a minimum of 50 CEAs per year had significantly lower
      perioperative mortality/morbidity rates (1.9 versus 3.0 per cent; P = 0.032).
      Trusts with seven or more surgeons demonstrated lower AAA-related mortality rates
      (1.7 versus 2.7 per cent; P = 0.018). CONCLUSION: Data from the NVRSO suggest
      that the majority of hospital Trusts presently fail to meet the standards for
      vascular centre status. NVRSO data support a standard of more than 60 elective
      AAA repairs and 50 CEAs per Trust per year. A minimum of seven vascular surgeons
      per unit was associated with better outcomes. These data support the ongoing
      remodelling of vascular services in the UK.

PMID- 24687391
TI  - Functionalized carbon nanotube reinforced scaffolds for bone regenerative
      engineering: fabrication, in vitro and in vivo evaluation.
AB  - Designing biodegradable scaffolds with bone-compatible mechanical properties has
      been a significant challenge in the field of bone tissue engineering and
      regenerative engineering. The objective of this work is to improve the polymeric
      scaffold's mechanical strength by compositing it with mechanically superior
      carbon nanotubes. Poly(lactide-co-glycolide) (PLGA) microsphere scaffolds exhibit
      mechanical properties in the range of human cancellous bone. On the other hand,
      carbon nanotubes have outstanding mechanical properties. The aim of this study is
      to improve further the mechanical strength of PLGA scaffolds such that they may
      be applicable for a wide range of load-bearing repair and regeneration
      applications. We have formed composite microspheres of PLGA containing pristine
      and modified (with hydroxyl (OH), carboxylic acid (COOH)) multi-walled carbon
      nanotubes (MWCNTs), and fabricated them into three-dimensional porous scaffolds.
      Results show that by adding only 3% MWCNTs, the compressive strength and modulus
      was significantly increased (35 MPa, 510.99 MPa) compared to pure PLGA scaffolds
      (19 MPa and 166.38 MPa). Scanning electron microscopy images showed excellent
      cell adhesion and proliferation. In vitro studies exhibited good cell viability,
      proliferation and mineralization. The in vivo study, however, indicated
      differences in inflammatory response throughout the 12 weeks of implantation,
      with OH-modified MWCNTs having the least response, followed by unmodified and
      COOH-modified exhibiting a more pronounced response. Overall, our results show
      that PLGA scaffolds containing water-dispersible MWCNTs are mechanically stronger
      and display good cellular and tissue compatibility, and hence are potential
      candidates for load-bearing bone tissue engineering.

PMID- 24687394
TI  - China to investigate widespread drugging of kindergarten children.

PMID- 24687395
TI  - Secondary diabetic ketoacidosis and severe hypoglycaemia in patients with
      established type 1 diabetes mellitus in China: a multicentre registration study.
AB  - BACKGROUND: Diabetic ketoacidosis (DKA) and severe hypoglycaemia are common acute
      complications of type 1 diabetes mellitus (T1DM). This study aimed to determine
      the incidence of, and risk factors for, these complications in Chinese patients
      with established T1DM. METHODS: This cross-sectional study recruited patients
      with established T1DM from 16 centres in Guangdong Province, China. Incidence
      rates were expressed as episodes/100 patient-years. Regression models identified
      risk factors for the occurrence and recurrence of secondary DKA and severe
      hypoglycaemia. RESULTS: A total of 611 patients with established T1DM (53.7%
      women) were recruited. The incidence of secondary DKA and severe hypoglycaemia
      was 26.4 (22.4, 31.0) and 68.8 (62.2, 76.0)/100 patient-years, respectively.
      Significant risk factors for secondary DKA were female gender [relative risk (RR)
      = 2.12], medical reimbursement rate <50% (RR = 1.84), uncontrolled diet (RR =
      1.76), smoking (RR = 2.18) and poor glycaemic control [glycated haemoglobin A1c
      (HbA1c)/1.0% increase; RR = 1.15]. Overweight/obesity was a protective factor (RR
      = 0.57). Significant risk factors for severe hypoglycaemia included male gender
      (RR = 1.71), medical reimbursement rate < 50% (RR = 1.36), longer duration of
      T1DM (per 5-year increase, RR = 1.22), underweight (RR = 1.44), uncontrolled diet
      ('never controlled' or 'sometimes controlled' vs. 'usually controlled', RR = 2.09
      or 2.02, respectively), exercise <150 min/week (RR = 1.66), presence of
      neuropathy (RR = 1.89), smoking (RR = 1.48) and lower HbA1c values (per 1.0%
      decrease, RR = 1.46). Overweight/obesity was a protective factor (RR = 0.62).
      Additionally, 34.4% of secondary DKA and 81.1% of severe hypoglycaemia episodes
      occurred in 3.8% and 16.2% patients with recurrent events (>=two episodes),
      respectively. CONCLUSIONS: The results indicate that secondary DKA and severe
      hypoglycaemia occur at high rates in Chinese patients with established T1DM and
      that recurrence is likely to occur in high-risk patients. Comprehensive
      management of T1DM should include recommendations to control modifiable risk
      factors.

PMID- 24687396
TI  - Continuous outpatient terlipressin infusion for hepatorenal syndrome as a bridge
      to successful liver transplantation.

PMID- 24687397
TI  - Effect of nitric oxide on microRNA-155 expression in human hepatic epithelial
      cells.
AB  - OBJECTIVE: Nitric oxide (NO) is a signaling molecule and regulator of immunity
      and inflammation. MicroRNAs (miRNAs) regulate gene transcription and are involved
      in inflammatory processes and cancer. This study sought to determine if NO
      activity affects miRNA expression. METHODS: Human liver epithelial (HepG2) cells
      were treated with the NO-releasing S-nitroso-N-acetylpenicillamine (SNAP) 100 MUM
      for 4 h and subjected to microarray analysis. To examine the underlying
      mechanisms, cells were exposed to cGMP analog 8-bromo-cGMP, protein kinase
      inhibitor Rp-*-Br-PET-cGMPS (Rp-PET), or nitric synthase inhibitor L-NAME and
      evaluated with RT-PCR. RESULTS: MiR-155 was the only miRNA of the 887 arrayed
      that showed a change in expression after SNAP treatment. Incubation of the cells
      with 8-bromo-cGMP increased miR-155 expression 4.0 +/- 0.7-fold (p < 0.05); Rp
      PET before SNAP had a dual, concentration-dependent effect. SNAP treatment
      induced a 3.1 +/- 0.7-fold change in miRNA-155 expression, Rp-PET 25 MUM, a 7.3
      +/- 2.2-fold change, and Rp-PET 100 MUM, a 0.79 +/- 0.09-fold change (SNAP vs
      SNAP + Rp-PET, p < 0.05). In unstimulated cells, Rp-PET or L-NAME treatment
      increased miR-155 expression by 3.5 +/- 0.7-fold and 5.6 +/- 2.2-fold,
      respectively (p < 0.05). CONCLUSION: In HepG2 cells, exogenous NO increases miR
      155 expression, but endogenous basal NO inhibits it. Both effects are mediated
      via cGMP/PKG signaling. The upregulation of miR-155 by NO provides a new link
      between NO, inflammation, and cancer.

PMID- 24687398
TI  - Serum level of macrophage migration inhibitory factor (MIF) in Egyptians with
      alopecia areata and its relation to the clinical severity of the disease.
AB  - BACKGROUND: Alopecia areata (AA) is a common dermatological problem that
      manifests as sudden loss of hair without any inflammation or scarring. Various
      cytokines are implicated in the pathogenesis of this disease. Macrophage
      migration inhibitory factor (MIF) is located at an upstream position in the
      events leading to the possible dysregulated immuno-inflammatory responses, and
      the high level of this cytokine in AA may suggest a role of MIF in the
      pathogenesis of AA. METHODS: This case-control study was carried out on 31 AA
      patients with different grades of severity and 15 apparently healthy subjects.
      Serum MIF level was measured by ELISA, and was correlated with the clinical
      severity of the disease using SALT (severity of alopecia tool) scoring system.
      RESULTS: In this study, there was a significant elevation in serum MIF levels in
      AA patients in comparison with controls. There was also a positive correlation
      between MIF levels and clinical severity and disease duration. CONCLUSION: MIF
      seems to have an essential role in the etiopathogenesis of AA. So, it is
      considered to be a promising target in the therapy of autoimmune diseases and as
      a future predictor of alopecia activity. Anti-MIF therapy might be added as one
      of the new biological treatments for AA.

PMID- 24687399
TI  - Flexible molecular-scale electronic devices composed of diarylethene
      photoswitching molecules.

PMID- 24687400
TI  - REKINDLE: robust extraction of kurtosis INDices with linear estimation.
AB  - PURPOSE: Recent literature shows that diffusion tensor properties can be
      estimated more accurately with diffusion kurtosis imaging (DKI) than with
      diffusion tensor imaging (DTI). Furthermore, the additional non-Gaussian
      diffusion features from DKI can be sensitive markers for tissue characterization.
      Despite these benefits, DKI is more susceptible to data artifacts than DTI due to
      its increased model complexity, higher acquisition demands, and longer scanning
      times. To increase the reliability of diffusion tensor and kurtosis estimates, we
      propose a robust estimation procedure for DKI. METHODS: We have developed a
      robust and linear estimation framework, coined REKINDLE (Robust Extraction of
      Kurtosis INDices with Linear Estimation), consisting of an iteratively reweighted
      linear least squares approach. Simulations are performed, in which REKINDLE is
      evaluated and compared with the widely used RESTORE (Robust EStimation of Tensors
      by Outlier REjection) method. RESULTS: Simulations demonstrate that in the
      presence of outliers, REKINDLE can estimate diffusion and kurtosis indices
      reliably and with a 10-fold reduction in computation time compared with RESTORE.
      CONCLUSION: We have presented and evaluated REKINDLE, a linear and robust
      estimation framework for DKI. While REKINDLE has been developed for DKI, it is by
      design also applicable to DTI and other diffusion models that can be linearized.

PMID- 24687401
TI  - Prevalence of hyperuricemia among Chinese adults: a national cross-sectional
      survey using multistage, stratified sampling.
AB  - BACKGROUND: Hyperuricemia is a non-communicable disease that threatens human
      health, and its prevalence has been increasing in recent decades. However, there
      have been no national surveys about hyperuricemia performed in China. We aimed to
      investigate the prevalence of hyperuricemia and its risk factors in Chinese
      adults. METHODS: Using data from 36,348 participants aged 18 years and older from
      the China National Survey of Chronic Kidney Disease (a nationwide cross-sectional
      survey with a randomized, multistage, stratified sampling strategy), we
      investigated the prevalence of hyperuricemia. Male subjects with serum uric acid
      >=416.0 MUmol/l (7.0 mg/dl) and female subjects with >=357.0 MUmol/l (6.0 mg/dl)
      were diagnosed with hyperuricemia. The prevalence of hyperuricemia was
      calculated, and the factors associated with hyperuricemia were analyzed using
      logistic regression. RESULTS: The adjusted prevalence of hyperuricemia among
      Chinese adults in 2009-2010 was 8.4 % [95 % confidence interval (CI) 8.0-8.8 %],
      and it was 9.9 % (9.2-10.6 %) in men and 7.0 % (6.5-7.5 %) in women. The
      prevalence was much higher among urban than rural residents (14.9 vs. 6.6 %, p <
      0.01). Areas with high per capita gross domestic product (GDP) levels had higher
      prevalence of hyperuricemia. In the multivariate regression model, the estimated
      glomerular filtration rate was inversely associated with hyperuricemia. Alcohol
      consumption, body mass index and serum triglyceride levels were positively
      correlated with hyperuricemia. Other factors independently correlated with
      hyperuricemia were age, sex, education level, area of residence, and economic
      development. In order to demonstrate the discriminatory power for hyperuricemia
      of the risk factors all together, we calculated the probabilities by logistic
      regression analysis, which represented the combined effects of these risk
      factors. Then, receiver operating characteristic analysis was used to demonstrate
      the value of the probabilities for hyperuricemia diagnosis. Finally, ROC curve
      analysis revealed the area under the curve was 0.746 (95 % CI 0.739-0.754),
      statistically significant for the association with hyperuricemia of these risk
      factors considered all together (p < 0.001). CONCLUSIONS: Hyperuricemia is
      prevalent in the economically developed areas of China. Our report indicates the
      feasibility of studying the influence that economic changes have on the
      prevalence of hyperuricemia.

PMID- 24687402
TI  - Serum hepcidin-25 and response to intravenous iron in patients with non-dialysis
      chronic kidney disease.
AB  - BACKGROUND: Hepcidin-25 is an iron regulator which reduces iron absorption and
      promotes sequestration in the reticulo-endothelial system. We investigated
      hepcidin and traditional iron storage marker utility in predicting haemoglobin
      increment following bolus intravenous iron. METHODS: The cohort included 129
      consecutive non-dialysis chronic kidney disease patients that attended for
      intravenous iron over a 6-month period. Serum hepcidin-25 levels (determined by
      mass spectrometry) pre iron infusion and 6 weeks post were compared with ferritin
      and transferrin saturation in multivariate models. RESULTS: Log10 ferritin
      [coefficient 0.559 (0.435-0.684) p < 0.001] and log10 high-sensitive C-reactive
      protein [coefficient 0.092 (0.000-0.184) p = 0.049] were significantly associated
      with baseline log10 hepcidin-25 levels. Log10 estimated glomerular filtration
      rate was the only independent determinant of pre-infusion haemoglobin
      [coefficient 1.37 (0.16-2.59) p = 0.027]. Log10 hepcidin-25 was an independent
      predictor of haemoglobin increment 6 weeks following iron infusion [coefficient 
      0.84 (-1.38 to -0.31) p = 0.002]. Ferritin, transferrin saturation and hepcidin
      had similar predictive utility for a 1 g/dl haemoglobin increase (c-statistics:
      0.68, 0.70, 0.69). CONCLUSIONS: Hepcidin is an iron sensor marker which predicts
      the magnitude of haemoglobin increment following protocolised intravenous iron
      infusion. Although displaying similar predictive performance to ferritin and
      transferrin saturation, hepcidin may also play a mechanistic role.

PMID- 24687403
TI  - Treatment of calcium nephrolithiasis in the patient with hyperuricosuria.
AB  - Nearly one-third of patients with calcium stones have hyperuricosuria. In vitro
      studies and clinical trials have investigated the relationship between uric acid
      and calcium stones, but the association between hyperuricosuria and calcium stone
      formation in patients is still being debated. Uric acid appears to cause salting
      out of calcium oxalate in human urine. However, the importance of this in vitro
      phenomenon to the proposed association is not supported in cross-sectional
      observational studies. A small placebo-controlled randomized clinical trial
      showed that allopurinol decreased the rate of recurrent calcium oxalate calculi
      in patients with hyperuricosuria and normocalciuria. An assessment of the effect
      of combination therapy of allopurinol with indapamide showed no additive effect.
      Allopurinol may have antioxidant effects that are responsible for its reducing
      calcium stone formation, which are independent of xanthine oxidase inhibition. In
      addition, a newer xanthine oxidoreductase inhibitor, febuxostat, may also be
      effective in the prevention of calcium stones, as it reduces urinary uric acid
      excretion. 

PMID- 24687404
TI  - Reduction in adipose tissue volume using a new high-power radiofrequency
      technology combined with infrared light and mechanical manipulation for body
      contouring.
AB  - A growing patient demand for a youthful skin appearance with a favorable body
      shape has led to the recent development of new noninvasive body contouring
      techniques. We have previously demonstrated that the combination of bipolar
      radiofrequency (RF) and optical energies with tissue manipulation is an efficient
      reshaping modality. Here, we investigated the efficacy and safety of a new high
      power version of this combined technology, in terms of adipose tissue reduction
      and skin tightening. Thirty-five patients received one treatment per week over 6
      weeks to their abdomen/flank, buttock, or thigh areas and were followed up to 3
      months post completion of the treatment protocol. This new device has an
      increased power in the bipolar RF, as this parameter appears to be the most
      important energy modality for volume reduction. Patient circumferences were
      measured and comparisons of baseline and post treatment outcomes were made.
      Diagnostic ultrasound (US) measurements were performed in 12 patients to evaluate
      the reduction in adipose tissue volume, and a cutometer device was used to assess
      improvements in skin tightening. We observed a gradual decline in patient
      circumferences from baseline to post six treatments. The overall body shaping
      effect was accompanied with improvement in skin tightening and was clearly
      noticeable in the comparison of the before and after treatment clinical
      photographs. These findings correlated with measurements of adipose tissue volume
      and skin firmness/elasticity using diagnostic US and cutometer, respectively. The
      thickness of the fat layer showed on average a 29% reduction between baseline and
      the 1-month follow up. The average reduction in the circumference of the
      abdomen/flanks, buttocks, and thighs from baseline to the 3-month follow-up was
      1.4, 0.5, and 1.2 cm, respectively, and 93% of study participants demonstrated a
      1-60% change in fat layer thickness. Patients subjectively described comfort and
      satisfaction from treatment, and 97% of them were satisfied with the results at
      the follow-up visit. The application of high-power RF energy combined with
      infrared (IR), mechanical massage, and vacuum appears to be an effective modality
      for the reduction in circumferences of the abdomen/flank, buttock and thigh
      regions, and the improvement of skin appearance. The present study performed with
      a new device suggests that the underlying mechanism of action is reduction in the
      subcutaneous adipose tissue volume and intensification of dermal matrix density.

PMID- 24687405
TI  - The dynamic duo: combining NMR and small angle scattering in structural biology.
AB  - Structural biology provides essential information for elucidating molecular
      mechanisms that underlie biological function. Advances in hardware, sample
      preparation, experimental methods, and computational approaches now enable
      structural analysis of protein complexes with increasing complexity that more
      closely represent biologically entities in the cellular environment. Integrated
      multidisciplinary approaches are required to overcome limitations of individual
      methods and take advantage of complementary aspects provided by different
      structural biology techniques. Although X-ray crystallography remains the method
      of choice for structural analysis of large complexes, crystallization of flexible
      systems is often difficult and does typically not provide insights into
      conformational dynamics present in solution. Nuclear magnetic resonance
      spectroscopy (NMR) is well-suited to study dynamics at picosecond to second time
      scales, and to map binding interfaces even of large systems at residue resolution
      but suffers from poor sensitivity with increasing molecular weight. Small angle
      scattering (SAS) methods provide low resolution information in solution and can
      characterize dynamics and conformational equilibria complementary to
      crystallography and NMR. The combination of NMR, crystallography, and SAS is,
      thus, very useful for analysis of the structure and conformational dynamics of
      (large) protein complexes in solution. In high molecular weight systems, where
      NMR data are often sparse, SAS provides additional structural information and can
      differentiate between NMR-derived models. Scattering data can also validate the
      solution conformation of a crystal structure and indicate the presence of
      conformational equilibria. Here, we review current state-of-the-art approaches
      for combining NMR, crystallography, and SAS data to characterize protein
      complexes in solution. 

PMID- 24687406
TI  - Cardiovascular imaging 2013 in the International Journal of Cardiovascular
      Imaging.

PMID- 24687407
TI  - MDCT evaluation of atherosclerotic coronary artery disease: what should
      radiologists know?
AB  - As an important tool for diagnosing acute coronary syndrome and stable angina,
      coronary CT angiography has been increasingly being performed in patients
      presenting with atypical chest pain. In order to help treating patients more
      efficiently, it is crucial for radiologists to have a comprehensive understanding
      about mechanisms and clinical aspects as well as CT findings of coronary
      atherosclerosis per se. A thorough understanding and optimal performance of
      coronary CT angiography may lead to reduction of unjustified downstream testing.
      This article provides a clinical and radiological overview of coronary
      atherosclerosis, and a practical guideline about how to interpret degree of
      stenosis on coronary CT angiography. 

PMID- 24687408
TI  - A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus
      cisplatin in patients with advanced malignant pleural mesothelioma.
AB  - PURPOSE: Low-dose, prolonged infusion of gemcitabine has effects similar to
      standard doses in several cancers. We evaluated the toxicity and efficacy of low
      dose gemcitabine in prolonged infusion plus cisplatin in patients with advanced
      pleural mesothelioma. METHODS: Patients with mesothelioma received gemcitabine
      (250 mg/m(2)) in a 6-h infusion plus cisplatin (35 mg/m(2)) on days 1 and 8 every
      three weeks. We used the modified response evaluation criteria in solid tumours.
      This study is registered in clinical trials (NCT01869023). RESULTS: We included
      39 patients; 82.1 % were low risk according to the European Organisation for
      Research and Treatment of Cancer prognostic group. Partial response was observed
      in 53.8 % (21/39), stable disease in 33.3 % (13/39) and progression in 12.8 %
      (5/39). The median progression-free survival was 6.9 months (95 % CI 3.2-10.6
      months), and the associated factors were the EORTC risk and histology. The median
      overall survival was 20.7 months (95 % CI 10.7-30.8 months). The functional,
      physical and emotional roles and dyspnoea, insomnia and pain symptom scales
      improved. The most commonly graded 3/4 side effects were neutropenia (24.4 %),
      lymphopenia (14.6 %), thrombocytopenia (14.7 %) and anaemia (12.2 %).
      CONCLUSIONS: Low-dose, prolonged gemcitabine infusion plus cisplatin has
      acceptable toxicity and high efficacy with improved quality of life, representing
      an affordable regimen for the low-income population.

PMID- 24687409
TI  - Effects of aromatase inhibitors and body mass index on steroid hormone levels in
      women with early and advanced breast cancer.
AB  - BACKGROUND: Aromatase inhibitors (AIs) are central to the management of oestrogen
      receptor-positive breast cancer in the adjuvant and metastatic setting. Levels of
      circulating steroid hormones (SHs) were measured in patients established on AIs
      to investigate: the influence of body mass index (BMI) in both the adjuvant and
      metastatic setting; the class of AI utilized in the adjuvant setting (steroidal
      versus non-steroidal); and differences in SH levels between women treated
      adjuvantly and those receiving a second-line AI for locally advanced/metastatic
      disease. METHODS: Plasma levels of androstenedione, 5-androstene-3beta,17beta
      diol, dehydroepiandrosterone, oestradiol and testosterone were measured by
      radioimmunoassay in women with breast cancer who were receiving AIs in either an
      adjuvant or a metastatic setting. Differences between mean SH levels by class of
      AI, BMI, and second-line versus adjuvant therapy were assessed. RESULTS: Sixty
      four women were receiving AI therapy, 45 (70 per cent) in an adjuvant setting and
      19 (30 per cent) were taking a second-line AI. There was no significant
      correlation between BMI and SH levels. However, BMI was significantly higher in
      the second-line AI cohort compared with the adjuvant cohort (29.8 versus 26.2
      kg/m2 respectively; P = 0.026). In the adjuvant setting, patients receiving a
      steroidal AI had significantly higher levels of all five hormones (P < 0.050). In
      the second-line AI cohort, oestradiol levels were significantly higher than in
      the adjuvant cohort (4.5 versus 3.3 pg/ml respectively; P = 0.022). Multivariable
      analysis adjusted for BMI confirmed the higher residual oestradiol level in the
      second-line AI group (P = 0.063) and a significantly higher androstenedione level
      (P = 0.022). CONCLUSION: Residual levels of SH were not significantly influenced
      by BMI. However, the significant differences in residual SH levels between the
      second-line and adjuvant AI cohort is of relevance in the context of resistance
      to AI therapy, and warrants further investigation.

PMID- 24687410
TI  - CRF1 receptor-deficiency induces anxiety-like vulnerability to cocaine.
AB  - RATIONALE: The intake of psychostimulant drugs may induce cognitive dysfunction
      and negative affective-like states, and is associated with increased activity of
      stress-responsive systems. The corticotropin-releasing factor (CRF) system
      mediates neuroendocrine, behavioural and autonomic responses to stressors, and
      might be implicated in substance-related disorders. CRF signalling is mediated by
      two receptor types, named CRF1 and CRF2. OBJECTIVES: The present study aims to
      elucidate the role for the CRF1 receptor in cognitive dysfunction and anxiety
      like states induced by cocaine. RESULTS: The genetic inactivation of the CRF1
      receptor (CRF1+/- and CRF1-/-) does not influence recognition memory in drug
      naive mice, as assessed by the novel object recognition (NOR) test. Moreover, the
      chronic administration of escalating doses of cocaine (5-20 mg/kg, i.p.) induces
      NOR deficits, which are unaffected by CRF1 receptor-deficiency. However, the same
      drug regimen reveals an anxiety-like vulnerability to cocaine in CRF1-/- but not
      in wild-type or CRF1+/- mice, as assessed by the elevated plus maze test.
      CONCLUSIONS: The present findings indicate dissociation of cognitive dysfunction
      and anxiety-like states induced by cocaine. Moreover, they unravel a novel
      mechanism of vulnerability to psychostimulant drugs.

PMID- 24687411
TI  - MDMA administration during adolescence exacerbates MPTP-induced cognitive
      impairment and neuroinflammation in the hippocampus and prefrontal cortex.
AB  - RATIONALE: We have recently shown that chronic exposure to 3,4
      methylenedioxymethamphetamine (MDMA, "ecstasy") of adolescent mice exacerbates
      dopamine neurotoxicity and neuroinflammatory effects elicited by 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the substantia nigra and striatum at
      adulthood. OBJECTIVES: The present study investigated whether the amplification
      of MPTP effects by previous treatment with MDMA extends to the limbic and
      cortical regions and consequently affects cognitive performance. METHODS: Mice
      received MDMA (10 mg/kg, twice a day/twice a week) for 9 weeks, followed by MPTP
      (20 mg/kg * 4 administrations), starting 2 weeks after MDMA discontinuation.
      Complement type 3 receptor (CD11b) and glial fibrillary acidic protein (GFAP)
      were evaluated by immunohistochemistry in both the hippocampus and the medial
      prefrontal cortex (mPFC) to measure microglia and astroglia activation. These
      neurochemical evaluations were paired with an assessment of cognitive performance
      by means of the novel object recognition (NOR) and spontaneous alternation tasks.
      RESULTS: MPTP administration to MDMA-pretreated mice elicited a stronger
      activation of CD11b and GFAP in both the hippocampus and the mPFC compared with
      either substance administered alone. Furthermore, NOR performance was lower in
      MDMA-pretreated mice administered MPTP compared with mice that received either
      substance alone. CONCLUSIONS: These results demonstrate that MDMA-MPTP negative
      interactions extend to the limbic and cortical regions and may result in
      cognitive impairment, providing further evidence that exposure to MDMA may
      amplify the effects of later neurotoxic insults.

PMID- 24687412
TI  - Effects of ceftriaxone on ethanol intake: a possible role for xCT and GLT-1
      isoforms modulation of glutamate levels in P rats.
AB  - RATIONALE: Evidence suggests that glutamate transporter 1 (GLT-1) and
      cystine/glutamate exchanger transporter (xCT) are critical in maintaining
      glutamate homeostasis. We have recently demonstrated that ceftriaxone treatment
      induced upregulation of GLT1 levels and attenuated ethanol intake; however, less
      is known about the involvement of xCT on ethanol intake. In this study, we
      investigated the effects of ceftriaxone on the levels of xCT in both continuous
      and relapse-like ethanol drinking, as well as GLT-1 isoforms, and glutamate
      aspartate transporter (GLAST) in relapse-like ethanol intake. METHODS: P rats
      received free choice of 15 and 30 % ethanol and water for 5 weeks and then
      deprived of ethanol for 2 weeks. Rats were treated with ceftriaxone (100 mg/kg,
      i.p.) or saline during the last 5 days of the 2-week deprivation period. After
      deprivation period, P rats were re-exposed to free choice of 15 and 30 % ethanol
      and water for nine consecutive days. A second group of P rats was given
      continuous ethanol access for 5 weeks, then ceftriaxone (100 mg/kg, i.p.) or
      saline throughout the week 6. RESULTS: Ceftriaxone significantly attenuated
      relapse-like ethanol intake. Importantly, this effect of ceftriaxone was
      associated in part with upregulation of the levels of GLT-1a and GLT-1b isoforms
      and xCT in the prefrontal cortex (PFC) and the nucleus accumbens (NAc). There
      were no significant differences in GLAST expression among all groups. We also
      found that ceftriaxone treatment increased xCT levels in both PFC and NAc in
      continuous ethanol intake. CONCLUSION: These findings suggest that xCT and GLT-1
      isoforms might be target proteins for the treatment of alcohol dependence.

PMID- 24687414
TI  - Adiponectin and Aldosterone in Left Ventricular Hypertrophy: An Intriguing
      Interplay.

PMID- 24687413
TI  - The role of polymorphisms of genes CXCL12/CXCR4 and MIF in the risk development
      IBD the Polish population.
AB  - Inflammatory bowel disease (IBD) are characterized recurrent inflammation of
      gastrointestinal tract. The etiology and pathogenesis this disease is currently
      unclear, but it has become evident that immune and genetic factors are involved
      in this process. The aim of this study was to determine whether gene
      polymorphisms: MIF-173 G/C; CXCL12-801 G/A and CXCR4 C/T exon 2 position of
      rs2228014 is associated with susceptibility to IBD. A total of 286 patients were
      examined with IBD, including 152 patients with ulcerative colitis and 134 with
      Crohn's disease (CD) and 220 healthy subjects were recruited from the Polish
      population. Genotyping for polymorphisms in CXCL12/CXCR4 and MIF was performed by
      RFLP-PCR. Statistical significance was found for polymorphisms CXCR4, a receptor
      gene for CXCL12 genotypes and alleles in CD and for genotype C/T and T allele in
      ulcerative colitis with respect to control. This confirms the effect of CXCL12
      gene. The interplay between CXCL12 and its receptor CXCR4 affects homeostasis and
      inflammation in the intestinal mucosa. Three-gene analysis in CD confirmed the
      association of genotype GGGGCT. Statistical analysis of clinical data of patients
      with ulcerative colitis showed significant differences in the distribution of
      genotype C/T and T allele for CXCR4 in the left-side colitis. Having CXCR4/CXCL12
      chemokine axis polymorphisms may predispose to the development of IBD. Activation
      can also be their defensive reaction to the long-lasting inflammation. 

PMID- 24687415
TI  - Saudi Atrial Fibrillation Survey: national, observational, cross-sectional survey
      evaluating atrial fibrillation management and the cardiovascular risk profile of
      patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The
      Saudi Atrial Fibrillation Survey registry was designed to provide epidemiological
      and clinical data on patients with AF. The registry included 400 consecutive
      patients who met the eligibility criteria. Control of AF at the time of the
      initial visit was achieved by 211 (52.75%) patients. Cardiovascular risk profile
      of the patients with AF was smoking 92 (23.5%), hypertension 253 (63.25%),
      diabetes 192 (48%), and dyslipidemia 173 (44%). Rate control was the most
      frequent management strategy (in 265 patients, 66.2%) whereas rhythm control was
      chosen in 48 (12%) patients. Both strategies were attempted in 5 (1.2%) patients.
      This is the first nationwide registry of patients with AF in Saudi Arabia.
      Compared to developed countries, our patients with AF are relatively young and
      have higher rates of diabetes and rheumatic heart disease. Rate control is the
      main strategy currently used for managing AF. 

PMID- 24687416
TI  - Management of acute cholecystitis in cancer patients: a comparative effectiveness
      approach.
AB  - BACKGROUND: Host factors and therapy characteristics predispose cancer patients
      to a high risk of acute cholecystitis. Management of cholecystitis is often
      difficult given complex decision making involving the underlying cancer, possible
      interruption of treatment, and surgical fitness of the patient. METHODS: A
      management pathway was developed for cholecystitis in cancer patients which
      incorporated patient-specific survival and risks of recurrence. Estimates were
      obtained from a multistage systematic review. A decision tree with a lifetime
      horizon was constructed to compare conventional strategies [conservative
      treatment (CT), percutaneous cholecystostomy (PC) and definitive cholecystectomy
      (DC)] with the new pathway (NP). The decision tree was optimized for highest
      estimated survival. Sensitivity analyses were performed. RESULTS: In low surgical
      risk patients with cancer-specific survival of 12 months, the NP yielded
      estimated survivals of 11.9 versus 11.8 (CT) versus 11.8 (PC) versus 11.9 months
      for the DC arm. For high-risk patients, the estimated survival was 11.6 (NP), 9.9
      (DC), 11.4 (PC), and 11 (CT) months, respectively. The decision to perform a DC
      at 6 weeks after a PC was optimum in patients expected to survive 24 months (23.2
      months from the NP) or with a shorter expected survival but a high recurrence
      risk (>20 %). Model estimates were robust in sensitivity analyses. CONCLUSIONS:
      Incorporation of the surgical risk and the risk of recurrent cholecystitis, while
      balancing the patient-specific survival and the impact of antineoplastic therapy
      in the management of cholecystitis yields improved survival. This work provides
      measures to evaluate surgical judgment, and can augment the physician-patient
      decision making.

PMID- 24687417
TI  - Completely abdominal intersphincteric resection for lower rectal cancer:
      feasibility and comparison of robot-assisted and open surgery.
AB  - BACKGROUND: Most previous studies of intersphincteric resection (ISR) adopted a
      two-stage procedure involving abdominal and transanal approaches. We performed
      completely abdominal ISR via open and a robot-assisted (RA) approaches as
      treatments for lower rectal cancer (LRC). The RA approach might enable deep
      dissection and facilitate ISR in patients with restrictive pelvic anatomy.
      METHODS: A consecutive cohort of 222 LRC patients who underwent completely
      abdominal ISR (RA ISR, n = 108; open ISR, n = 114) was enrolled prospectively,
      and their short-term outcomes were evaluated. RESULTS: In a multivariate
      analysis, ISR was performed more frequently in the RA than in the open group
      (82.6 vs. 67.9 %, p = 0.008). The number of harvested lymph nodes was >12 in both
      groups. A positive distal resection margin was not observed in either group, and
      a positive circumferential resection margin was found in one patient in the RA
      group. Overall morbidity did not differ between the groups. Moderate to severe
      sexual dysfunction occurred 2.7-fold more frequently in the open group (p =
      0.023) among male patients <=65 years. Mean Wexner's fecal incontinence scores at
      postoperative months 6 and 12 were greater in the open group than in the RA group
      (p < 0.05). CONCLUSIONS: Completely abdominal ISR may be feasible in the
      treatment of LRC, based on a short-term study. Furthermore, RA ISR had equivalent
      oncological outcomes and slightly improved functional recovery relative to open
      ISR.

PMID- 24687418
TI  - Does thermodynamic stability of peritoneal collagen change during laparoscopic
      cholecystectomies? A differential scanning calorimetry (DSC) study.
AB  - BACKGROUND: Carbon dioxide pneumoperitoneum used during laparoscopic surgeries
      alters the integrity of the peritoneum and results in denudation of the basal
      lamina that might cause altered immune response, inhibited fibrinolysis, hypoxia,
      and acidosis. The changes in the structure of pneumoperitoneum were described as
      bulging of mesothelial cells, irregular cell junction's cell membrane
      degradation, and mesodermal edema. As denaturation of peritoneal proteins
      reflects overall condition of its structure and interactions with the surrounding
      molecules, the physical status of collagen was assessed on the basis of
      parameters of thermal denaturation measured by DSC method. METHODS: Twenty-four
      female patients operated on due to cholelithiasis were enrolled in this study.
      Laparoscopic cholecystectomy was performed using standard four-trocar technique,
      and standard values of insufflated carbon dioxide pneumoperitoneum were used.
      After trocar placement, the first collection of peritoneal sample (sample A) was
      performed. The second peritoneal sample (sample B) was collected after the
      removal of gall bladder. Differential scanning calorimetry (Q200 calorimeter, TA
      Instruments) was performed on samples defrosted at room temperature. RESULTS: In
      all samples of peritoneum, a nonreversible endothermal process recognized as
      denaturation was observed. Sample B obtained at the end of surgery did not differ
      from sample A obtained at the beginning in terms of all parameters under study.
      Temperature of denaturation in A and B was correlated only marginally, but
      enthalpy and specific heat were significantly correlated. The analysis of data
      from DSC measurements did not reveal differences in physical stability of
      collagen in peritoneal samples obtained at the beginning and at the end of
      surgery. Significant negative correlations between duration of CO2
      pneumoperitoneum and enthalpy of denaturation in sample B were found.
      CONCLUSIONS: Differences in enthalpy of denaturation may reflect a quantitative
      relation between amount of native collagen molecules in the sample and other, non
      collagenous components or impaired collagen.

PMID- 24687419
TI  - Regenerative potential and anti-bacterial activity of tetracycline loaded
      apatitic nanocarriers for the treatment of periodontitis.
AB  - Current treatment of periodontal infections includes mechanical debridement,
      administration of antibiotics and bone grafting. Oral administration of
      antibiotics results in undesirable side effects, while current modes of local
      administration are affected by problems concerning allergic response to the
      polymeric carrier agents. We have developed an osteoconductive drug delivery
      system composed of apatitic nanocarriers capable of providing sustained delivery
      of drugs in the periodontium. Calcium deficient hydroxyapatite (CDHA)
      nanocarriers of different Ca/P ratios were synthesized and characterized using
      the x-ray diffraction method, transmission electron microscopy, inductively
      coupled plasma atomic emission spectroscopy, Fourier transform infrared
      spectroscopy and the BET gas isotherm method. Loading and release studies
      performed with tetracycline showed a sustained release of up to 88% in phosphate
      buffered saline over a period of five days. Antibacterial activity studies showed
      that the tetracycline loaded CDHA (TC-CDHA) nanocarriers were effective against
      S. aureus and E. coli bacteria. The biocompatibility of the TC-CDHA nanocarriers
      was demonstrated using an alamar blue assay and further characterized by cell
      uptake studies. Interestingly, cell uptake of drug loaded CDHA also increased the
      cellular proliferation of human periodontal ligament fibroblast cells. Hence, it
      can be concluded that the CDHA nanocarriers are ideal drug delivery agents and
      have bone regenerative potential for local periodontal applications. 

PMID- 24687420
TI  - Introduction to a special issue: eliminating health and safety inequities at
      work.

PMID- 24687421
TI  - A pilot proteomic study of protein markers in autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) diagnosis is increasing, with 1/88 children
      believed to be affected by the disorder, with a most recent survey suggesting
      numbers as high as 1/50. Treatment and understanding of ASD causes is a pressing
      health concern. ASD protein biomarkers may provide clues about ASD cause. Protein
      biomarkers for ASDs could be used for ASD diagnosis, subtyping, treatment
      monitoring, and identifying therapeutic targets. Here, we analyzed the sera from
      seven children with ASD and seven matched controls using Tricine gel
      electrophoresis (Tricine-PAGE) and LC-MS/MS. Overall, we found increased levels
      of apolipoproteins ApoA1 and ApoA4, involved in cholesterol metabolism and of
      serum paraoxanase/arylesterase 1, involved in preventing oxidative damage, in the
      sera of children with ASD, compared with their matched controls. All three
      proteins are predicted to interact with each other and are parts of high-density
      lipoproteins. Further studies are needed to validate these findings in larger
      subject numbers.

PMID- 24687423
TI  - A SxIP motif interaction at the microtubule plus end is important for processive
      retrograde axonal transport.
AB  - The retrograde transport of endosomes within axons proceeds with remarkable
      uniformity despite having to navigate a discontinuous microtubule network. The
      mechanisms through which this navigation is achieved remain elusive. In this
      report, we demonstrate that access of SxIP motif proteins, such as BPAG1n4, to
      the microtubule plus end is important for the maintenance of processive and
      sustained retrograde transport along the axon. Disruption of this interaction at
      the microtubule plus end significantly increases endosome stalling. Our study
      thus provides strong insight into the role of plus-end-binding proteins in the
      processive navigation of cargo within the axon. 

PMID- 24687424
TI  - Two types of martensitic phase transformations in magnetic shape memory alloys by
      in-situ nanoindentation studies.

PMID- 24687422
TI  - Transport and diffusion of Tau protein in neurons.
AB  - In highly polarized and elongated cells such as neurons, Tau protein must enter
      and move down the axon to fulfill its biological task of stabilizing axonal
      microtubules. Therefore, cellular systems for distributing Tau molecules are
      needed. This review discusses different mechanisms that have been proposed to
      contribute to the dispersion of Tau molecules in neurons. They include (1)
      directed transport along microtubules as cargo of tubulin complexes and/or motor
      proteins, (2) diffusion, either through the cytosolic space or along
      microtubules, and (3) mRNA-based mechanisms such as transport of Tau mRNA into
      axons and local translation. Diffusion along the microtubule lattice or through
      the cytosol appear to be the major mechanisms for axonal distribution of Tau
      protein in the short-to-intermediate range over distances of up to a millimetre.
      The high diffusion coefficients ensure that Tau can distribute evenly throughout
      the axonal volume as well as along microtubules. Motor protein-dependent
      transport of Tau dominates over longer distances and time scales. At low near
      physiological levels, Tau is co-transported along with short microtubules from
      cell bodies into axons by cytoplasmic dynein and kinesin family members at rates
      of slow axonal transport. 

PMID- 24687425
TI  - Women spend more of their life with a disability than men.

PMID- 24687426
TI  - Neutrophil-lymphocyte ratio in patients with familial Mediterranean fever.
AB  - BACKGROUND: Blood neutrophil-to-lymphocyte (N/L) ratio is an indicator of the
      overall inflammatory status of the body, and an alteration in N/L ratio may be
      found in patients with familial Mediterranean fever (FMF). The aim of this study
      was to investigate the interrelationship between N/L ratio and FMF. METHODS: One
      hundred and fifteen patients and controls were enrolled in the study. The cases
      in the study were categorized as FMF with attack, FMF with attack-free period,
      and controls. The neutrophil and lymphocyte counts were recorded, and the N/L
      ratio was calculated from these parameters. All patients were diagnosed according
      to Tel Hashomer criteria. RESULTS: A total of 79 FMF patients were included in
      the study and all subjects were receiving colchicine treatment at the time. The
      serum N/L ratios of active patients were significantly higher than those of
      attack-free FMF patients and controls (P < 0.001). The optimum N/L ratio cut-off
      point for active FMF was 2.63 with sensitivity, specificity, positive predictive
      value, and negative predictive value of 0.62 (0.41-0.80), 0.85 (0.72-0.93), 0.67
      (0.44-0.85), and 0.82 (0.69-0.91), respectively. The overall accuracy of the N/L
      ratio in determination of FMF patients during attack was 71%. CONCLUSION: Our
      results demonstrate that N/L ratio is higher in patients with active FMF compared
      with FMF patients in remission and controls, and a cut-off value of 2.63 can be
      used to identify patients with active FMF.

PMID- 24687428
TI  - Multiwell plate tools for controlling cellular alignment with grooved topography.
AB  - In many tissues, cells must be aligned for proper function. This alignment can
      occur at the cellular and/or subcellular (protein/molecular) level. The alignment
      of cytoskeletal components, in fact, precedes whole cell alignment. A variety of
      methods exist to manipulate cytoskeletal and whole cell alignment; one of the
      simplest and most predictable involves seeding adherent cells onto defined
      substrate topography. We present here two methods to create grooved multiwell
      plates: one involving microfabrication, which allows for custom design of
      substrate topography, and a simpler, inexpensive method using commercially
      available diffraction gratings. We also include methods for manual and automatic
      quantification of cell alignment. 

PMID- 24687427
TI  - Lixisenatide as add-on to oral anti-diabetic therapy: an effective treatment for
      glycaemic control with body weight benefits in type 2 diabetes.
AB  - BACKGROUND: Achieving recommended glycated haemoglobin (HbA1c ) targets in
      patients with type 2 diabetes mellitus (T2DM) requires effective control of
      fasting and post-prandial plasma glucose. As T2DM progresses, oral anti-diabetics
      are no longer sufficient to maintain glycaemic control. Five phase III studies in
      the GetGoal clinical trial programme assessed the efficacy of lixisenatide, a
      once-daily prandial glucagon-like peptide-1 receptor agonist, in combination with
      oral anti-diabetics in patients with T2DM insufficiently controlled using oral
      anti-diabetics. METHODS: A meta-analysis was performed of the results of five 24
      week clinical trials (comprising 2760 patients) concerning lixisenatide or
      placebo plus oral anti-diabetic therapy. The primary endpoint of these studies
      was change in HbA1c at week 24. Changes in fasting and post-prandial plasma
      glucose, and weight were also established as were the odds ratios for
      hypoglycaemia and composite safety and efficacy endpoints. Meta-analysis outcomes
      were assessed using a random effects model. All meta-analyses were performed
      using RevMan, version 5.1. RESULTS: Lixisenatide was significantly better than
      placebo in terms of achieving all endpoints in this meta-analysis, including the
      primary endpoint change in HbA1c at week 24, with p < 0.0001 for all endpoints.
      The mean number of symptomatic hypoglycaemic events per patient year was
      increased for patients in the lixisenatide versus placebo groups (p = 0.04).
      However, compared with patients in the placebo group, patients treated with
      lixisenatide were more likely to achieve composite efficacy and safety endpoints.
      CONCLUSIONS: This meta-analysis demonstrates that lixisenatide in combination
      with oral anti-diabetic therapy significantly improves outcomes combining
      efficacy and safety parameters in patients with T2DM.

PMID- 24687429
TI  - On the measurement of entropy production in living cells under an alternating
      electric field.

PMID- 24687430
TI  - Tracer kinetic modeling in myocardial perfusion quantification using MRI.
AB  - PURPOSE: To investigate and compare several quantification methods of myocardial
      perfusion measurements, paying special attention to the relation between the
      techniques and the required measurement duration. METHODS: Seven patients
      underwent contrast-enhanced rest and stress cardiac perfusion measurements at 3T.
      Three slices were acquired in each patient and were divided into 16 segments,
      leading to 112 rest and stress data curves, which were analyzed using various
      tracer kinetic models as well as a model-free deconvolution. Plasma flow, plasma
      volume, and myocardial perfusion reserve were analyzed for the complete
      acquisition as well as for the first pass data only. RESULTS: Deconvolution
      analysis yielded stable results for both rest and stress analysis, while Fermi
      and one compartment models agree well for first pass data (rest measurements
      only) and prolonged data acquisition (stress measurements only). More complex
      models do not yield satisfactory results for the short measurement times
      investigated in this study. CONCLUSIONS: When performing MRI-based quantification
      of myocardial perfusion, care must be taken that the method used is appropriate
      for the time frame under investigation. When a numerical deconvolution is used
      instead of tracer kinetic models, more stable results are obtained.

PMID- 24687431
TI  - Characterization of V-ATPase inhibitor-induced secretion of cysteine-rich with
      EGF-like domains 2.
AB  - We previously demonstrated that cysteine-rich with EGF-like domains 2 (CRELD2), a
      novel ER stress-inducible factor, is a secretory glycoprotein; however, the
      stimuli that induce CRELD2 secretion have not yet been characterized. In this
      study, we found that the perturbation of intravesicular acidification of
      cytoplasmic organelles in HEK293 cells stably expressing wild-type (wt) CRELD2
      induced its secretion. In particular, Concanamycin A (CMA) and Bafilomycin A1
      (Baf), inhibitors of vacuolar ATPase (V-ATPase), increased the secretion of
      CRELD2 without relying on its C-terminal structure. The levels of secretion of
      EGFP-fused CRELD2 (SP-EGFP-CRELD2), which consists of EGFP following the putative
      signal peptide (SP) sequence of CRELD2, from COS7 cells transiently transfected
      with this construct were also increased after each of the treatments, but their
      intracellular localization was barely affected by CMA treatment. Transient
      overexpression of 78-kDa glucose-regulated protein (GRP78) and protein disulfide
      isomerase (PDI) also increased the secretion of CRELD2 from HEK293 cells
      expressing wt CRELD2, whereas the perturbation of intravesicular acidification
      did not alter the expression of GRP78 and PDI in the HEK293 cells. We further
      studied the roles of intracellular calcium ions and the Golgi apparatus in the
      secretion of CRELD2 from HEK293 cells in which intravesicular acidification was
      perturbed. The treatment with calcium ionophore increased the secretion of wt
      CRELD2, while that with BAPTA-AM, an intracellular calcium chelator, did not
      reduce the CMA-induced CRELD2 secretion. By contrast, treatment with brefeldin A
      (BFA), which inhibits the transportation of proteins from the ER to the Golgi
      apparatus, almost completely abolished the secretion of wt CRELD2 from the HEK293
      cells. In conclusion, we demonstrated that the intravesicular acidification by V
      ATPase regulates the secretion of CRELD2 without relying on the balance of
      intracellular calcium ions and the expression of ER chaperones such as GRP78 and
      PDI. These findings concerning the role of V-ATPases in modulating the secretion
      of CRELD2, a novel ER stress-inducible secretory factor, may provide new insights
      into the prevention and treatment of certain ER stress-related diseases. 

PMID- 24687432
TI  - Ramachandran analysis of conserved glycyl residues in homologous proteins of
      known structure.
AB  - High conservation of glycyl residues in homologous proteins is fairly frequent.
      It is commonly understood that glycine tends to be highly conserved either
      because of its unique Ramachandran angles or to avoid steric clash that would
      arise with a larger side chain. Using a database of aligned 3D structures of
      homologous proteins we identified conserved Gly in 288 alignment positions from
      85 families. Ninety-six of these alignment positions correspond to conserved Gly
      residue with (phi, psi) values allowed for non-glycyl residues. Reasons for this
      observation were investigated by in-silico mutation of these glycyl residues to
      Ala. We found in 94% of the cases a short contact exists between the C(beta) atom
      of the introduced Ala with the atoms which are often distant in the primary
      structure. This suggests the lack of space even for a short side chain thereby
      explaining high conservation of glycyl residues even when they adopt (phi, psi)
      values allowed for Ala. In 189 alignment positions, the conserved glycyl residues
      adopt (phi, psi) values which are disallowed for Ala. In-silico mutation of these
      Gly residues to Ala almost always results in steric hindrance involving C(beta)
      atom of Ala as one would expect by comparing Ramachandran maps for Ala and Gly.
      Rare occurrence of the disallowed glycyl conformations even in ultrahigh
      resolution protein structures are accompanied by short contacts in the crystal
      structures and such disallowed conformations are not conserved in the homologues.
      These observations raise the doubt on the accuracy of such glycyl conformations
      in proteins. 

PMID- 24687433
TI  - The Mark Coventry Award: Trabecular metal tibial components were durable and
      reliable in primary total knee arthroplasty: a randomized clinical trial.
AB  - BACKGROUND: Although highly porous metals have demonstrated excellent bone
      ingrowth properties and so are an intriguing option for fixation in total knee
      arthroplasty (TKA), some surgeons are skeptical about the durability of
      uncemented tibial fixation and the potential for soft tissues to adhere to these
      porous metals and perhaps cause knee stiffness or pain. QUESTIONS/PURPOSES: The
      purpose of this study was to compare, in the context of a randomized clinical
      trial, a highly porous metal tibia compared with a traditional modular cemented
      tibia in terms of survivorship, Knee Society scores, range of motion (ROM), and
      complications. METHODS: From 2003 to 2006, 397 patients (age 67.8 +/- 8.7 years;
      54% female) were randomized to three groups: (1) traditional modular cemented
      tibia; (2) cemented highly porous metal tibia; and (3) uncemented highly porous
      metal tibia. The same posterior-stabilized femoral component and patella
      component were cemented in every case. Stratified randomization was done for
      surgeon, patient's age, sex, and body mass index. Survivorship at 5 years was
      compared between the groups, as were Knee Society scores, ROM, and complications.
      Radiographic assessment included alignment, radiolucency, and implant
      migration/loosening. Patients were followed until death, revision, or for a
      minimum of 2 years (mean, 5 years; range, 2-9 years). Four patients were lost to
      followup before 2 years. RESULTS: Highly porous metal tibias (both uncemented and
      cemented) were no different from traditional cemented modular tibial modular
      components in terms of survivorship at 5 years using a intention-to-treat
      analysis (96.8% [1]; 97.6% [2]; 96.7% [3]; p = 0.59). A per-protocol analysis
      revealed that no highly porous metal tibia was revised for aseptic loosening.
      Highly porous metal tibias performed comparably to traditional cemented modular
      tibias in terms of Knee Society scores, ROM, and the frequency of complications.
      CONCLUSIONS: At 5 years this randomized clinical trial demonstrated that highly
      porous metal tibias provided comparably durable fixation and reliable pain relief
      and restoration of function when compared with a traditional cemented modular
      tibia in TKA. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 24687434
TI  - Choosing between RT-qPCR and RNA-seq: a back-of-the-envelope estimate towards the
      definition of the break-even-point.

PMID- 24687435
TI  - Combined use of two membrane-potential-sensitive dyes for determination of the
      Galvani potential difference across a biomimetic oil/water interface.
AB  - The fluorescence behavior of anionic membrane-potential-sensitive dyes, bis-(1,3
      dibutylbarbituric acid) trimethine oxonol (DiBAC4(3)) and bis-(1,3
      diethylthiobarbituric acid)trimethine oxonol (DiSBAC2(3)), at a biomimetic 1,2
      dichloroethane (DCE)/water (W) interface was studied by the mean of potential
      modulated fluorescence (PMF) spectroscopy. The respective dyes gave a well
      defined PMF signal due to the adsorption/desorption at the DCE/W interface. It
      was also found that the potentials where the two dyes gave the PMF signals were
      different by about 100 mV. We then attempted a combined use of the two dyes for
      determination of the Galvani potential difference across the DCE/W interface.
      When 40 MUM DiBAC4(3) and 15 MUM DiSBAC2(3) were initially added to the W phase,
      distinctly different spectra were obtained for different interfacial potentials.
      The ratio of the PMF signal intensities at 530 and 575 nm (the fluorescence
      maximum wavelengths for the respective dyes) showed a clear dependence on the
      interfacial potential. These results suggested the potential utility of the
      combined use of two dyes for the determination of membrane potentials in vivo. 

PMID- 24687436
TI  - Mathematical modelling reveals properties of TcdC required for it to be a
      negative regulator of toxin production in Clostridium difficile.
AB  - The role of the protein TcdC in pathogenicity of the bacterium Clostridium
      difficile is currently unclear: conflicting reports suggest it is either a
      negative regulator of toxin production or, on the other hand, has no effect on
      virulence at all. We exploit a theoretical approach by taking what is known about
      the network of proteins surrounding toxin production by C. difficile and
      translating this into a mathematical model. From there it is possible to
      investigate a range of possible interactions (using numerical and asymptotic
      analyses), identifying properties of TcdC which would make it a realistic
      candidate as a toxin inhibitor. Our findings imply that if TcdC is really an
      inhibitor of toxin production then TcdC production should be at least as fast as
      that of the protein TcdR and TcdC should remain in the cells throughout growth.
      These are experimentally-testable hypotheses and are equally applicable to
      alternative candidates for toxin production inhibition. 

PMID- 24687438
TI  - Beyond the printed page: Leveraging social media to extend the Journal's
      influence.

PMID- 24687437
TI  - Prognostic impact of venous invasion in stage IB node-negative gastric cancer.
AB  - BACKGROUND: Little is known about risk factors for recurrence in stage IB gastric
      cancer without lymph node metastasis. The aims of this study were to determine
      prognostic factors associated with long-term survival and to clarify patterns of
      recurrence. METHODS: We retrospectively reviewed the medical records of 130
      patients with primary gastric cancer who underwent gastrectomy at Kitasato
      University East Hospital from 2001 through 2010 and analyzed clinicopathological
      characteristics associated with survival and patterns of recurrence. RESULTS: Of
      the 130 patients, 12 (9.2%) had recurrence, among whom 10 (83%) patients died.
      Four patients (3.1%) died of other diseases. The 5-year overall survival rate was
      89%. Of the 12 patients with recurrence, 7 (58%) had liver metastasis, 3 (25%)
      had distant lymph-node metastasis, 2 (17%) had peritoneal dissemination, and 1
      (8.3%) had locoregional recurrence. Patients with tumors more than 5 cm in
      diameter tended to have recurrence within 1 year. Patients who had recurrence
      more than 2 years after surgery tended to survive for longer than 5 years after
      recurrence. Moderate or marked venous invasion (v2 or v3) and age >65 years were
      significantly associated with relapse-free and overall survival on univariate
      analysis. On multivariate analysis, the only independent prognostic factor for
      relapse-free and overall survival was venous invasion. CONCLUSIONS: Moderate or
      marked venous invasion (v2 or v3) is an independent predictor of relapse-free and
      overall survival in stage IB node-negative gastric cancer. Postoperative adjuvant
      chemotherapy, currently not given to this subgroup of patients, may improve the
      outcomes of patients with stage IB node-negative gastric cancer, particularly
      when accompanied by venous invasion.

PMID- 24687439
TI  - Effects of error experience when learning to simulate hypernasality.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of error
      experience on the acquisition of hypernasal speech. METHOD: Twenty-eight healthy
      participants were asked to simulate hypernasality in either an errorless learning
      condition (in which the possibility for errors was limited) or an errorful
      learning condition (in which the possibility for errors was not limited). The
      nasality level of the participants' speech was measured with a nasometer and
      reflected by nasalance scores (in percentages). Errorless learners practiced
      producing hypernasal speech with a threshold nasalance score of 10% at the
      beginning, gradually increasing to a threshold of 50% at the end. The same set of
      threshold targets were presented to errorful learners but in a reversed order.
      Errors were defined by the proportion of speech with a nasalance score below the
      threshold. A retention test and a transfer test were administered. RESULTS:
      Relative to errorful learners, errorless learners displayed fewer errors and a
      higher mean nasalance score during acquisition. Furthermore, errorless learners
      outperformed errorful learners in both retention and transfer tests. CONCLUSION:
      The results suggest that errorless learning is more effective than errorful
      learning in acquiring a novel speech motor task that involves manipulation of the
      nasality level of speech.

PMID- 24687440
TI  - Using statistical process control charts to study stuttering frequency
      variability during a single day.
AB  - PURPOSE: Stuttering varies between and within speaking situations. In this study,
      the authors used statistical process control charts with 10 case studies to
      investigate variability of stuttering frequency. METHOD: Participants were 10
      adults who stutter. The authors counted the percentage of syllables stuttered
      (%SS) for segments of their speech during different speaking activities over a 12
      hr day. Results for each participant were plotted on control charts. RESULTS: All
      participants showed marked variation around mean stuttering frequency. However,
      there was no pattern of that variation consistent across the 10 participants.
      According to control charts, the %SS scores of half the participants were
      indicative of unpredictable, out-of-control systems, and the %SS scores of the
      other half of the participants were not. Self-rated stuttering severity and
      communication satisfaction correlated significantly and intuitively with the
      number of times participants exceeded their upper control chart limits.
      CONCLUSIONS: Control charts are a useful method to study how %SS scores might be
      applied to the study of stuttering variability during research and clinical
      practice. However, the method presents some practical problems, and the authors
      discuss how those problems can be solved. Solving those problems would enable
      researchers and clinicians to better plan, conduct, and evaluate stuttering
      treatments.

PMID- 24687442
TI  - Five decades of research in speech motor control: what have we learned, and where
      should we go from here?
AB  - PURPOSE: The author presents a view of research in speech motor control over the
      past 5 decades, as observed from within Ken Stevens's Speech Communication Group
      (SCG) in the Research Laboratory of Electronics at MIT. METHOD: The author
      presents a limited overview of some important developments and discoveries. The
      perspective is based largely on the research interests of the Speech Motor
      Control Group (SMCG) within the SCG; thus, it is selective, focusing on normal
      motor control of the vocal tract in the production of sound segments and
      syllables. It also covers the particular theories and models that drove the
      research. Following a brief introduction, there are sections on methodological
      advances, scientific advances, and conclusions. RESULTS: Scientific and
      methodological advances have been closely interrelated. Advances in
      instrumentation and computer hardware and software have made it possible to
      record and process increasingly large, multifaceted data sets; introduce new
      paradigms for feedback perturbation; image brain activity; and develop more
      sophisticated, computational physiological and neural models. Such approaches
      have led to increased understanding of the widespread variability in speech,
      motor-equivalent trading relations, sensory goals, and the nature of feedback and
      feedforward neural control mechanisms. CONCLUSIONS: Some ideas about important
      future directions for speech research are presented.

PMID- 24687443
TI  - Left lateralized enhancement of orofacial somatosensory processing due to speech
      sounds.
AB  - PURPOSE: Somatosensory information associated with speech articulatory movements
      affects the perception of speech sounds and vice versa, suggesting an intimate
      linkage between speech production and perception systems. However, it is unclear
      which cortical processes are involved in the interaction between speech sounds
      and orofacial somatosensory inputs. The authors examined whether speech sounds
      modify orofacial somatosensory cortical potentials that were elicited using
      facial skin perturbations. METHOD: Somatosensory event-related potentials in EEG
      were recorded in 3 background sound conditions (pink noise, speech sounds, and
      nonspeech sounds) and also in a silent condition. Facial skin deformations that
      are similar in timing and duration to those experienced in speech production were
      used for somatosensory stimulation. RESULTS: The authors found that speech sounds
      reliably enhanced the first negative peak of the somatosensory event-related
      potential when compared with the other 3 sound conditions. The enhancement was
      evident at electrode locations above the left motor and premotor area of the
      orofacial system. The result indicates that speech sounds interact with
      somatosensory cortical processes that are produced by speech-production-like
      patterns of facial skin stretch. CONCLUSION: Neural circuits in the left
      hemisphere, presumably in left motor and premotor cortex, may play a prominent
      role in the interaction between auditory inputs and speech-relevant somatosensory
      processing.

PMID- 24687444
TI  - An EMG study of the lip muscles during covert auditory verbal hallucinations in
      schizophrenia.
AB  - PURPOSE: Auditory verbal hallucinations (AVHs) are speech perceptions in the
      absence of external stimulation. According to an influential theoretical account
      of AVHs in schizophrenia, a deficit in inner-speech monitoring may cause the
      patients' verbal thoughts to be perceived as external voices. The account is
      based on a predictive control model, in which individuals implement verbal self
      monitoring. The authors examined lip muscle activity during AVHs in patients with
      schizophrenia to check whether inner speech occurred. METHOD: Lip muscle activity
      was recorded during covert AVHs (without articulation) and rest. Surface
      electromyography (EMG) was used on 11 patients with schizophrenia. RESULTS:
      Results showed an increase in EMG activity in the orbicularis oris inferior
      muscle during covert AVHs relative to rest. This increase was not due to general
      muscular tension because there was no increase of muscular activity in the
      forearm muscle. CONCLUSION: This evidence that AVHs might be self-generated inner
      speech is discussed in the framework of a predictive control model. Further work
      is needed to better describe how inner speech is controlled and monitored and the
      nature of inner-speech-monitoring-dysfunction. This will lead to a better
      understanding of how AVHs occur.

PMID- 24687445
TI  - Palatal morphology can influence speaker-specific realizations of phonemic
      contrasts.
AB  - PURPOSE: The purpose of this study was to further explore the understanding of
      speaker-specific realizations of the /s/-/?/ contrast in German in relation to
      individual differences in palate shape. METHOD: Two articulatory experiments were
      carried out with German native speakers. In the first experiment, 4 monozygotic
      and 2 dizygotic twin pairs were recorded by means of electromagnetic
      articulography. In the second experiment, 12 unrelated speakers were recorded by
      means of electropalatography. Interspeaker variability in the articulatory
      distance between the sibilants was measured and was correlated with several
      parameters of the palate shape. RESULTS: The results were twofold: (a) Similar
      palatal morphologies as found in monozygotic twins yield similar articulatory
      realizations of the /s/-/?/ contrast regarding vertical and horizontal distance
      of the target tongue tip positions, and (b) the realization of the contrast was
      influenced by palatal steepness, especially the inclination angle of the alveolo
      palatal region. Speakers with flat inclination angles mainly retracted their
      tongue to realize the contrast, whereas speakers with steep inclination angles
      also elevated their tongue. CONCLUSION: The articulatory realization of the
      sibilant contrast is influenced not only by speaker-specific auditory acuity, as
      previously observed, but also by palatal shape morphology, which affects the
      somatosensory feedback speakers receive.

PMID- 24687446
TI  - The distributed lambda (lambda) model (DLM): a 3-D, finite-element muscle model
      based on Feldman's lambda model; assessment of orofacial gestures.
AB  - PURPOSE: The authors aimed to design a distributed lambda model (DLM), which is
      well adapted to implement three-dimensional (3-D), finite-element descriptions of
      muscles. METHOD: A muscle element model was designed. Its stress-strain
      relationships included the active force-length characteristics of the lambda
      model along the muscle fibers, together with the passive properties of muscle
      tissues in the 3-D space. The muscle element was first assessed using simple
      geometrical representations of muscles in the form of rectangular bars. It was
      then included in a 3-D face model, and its impact on lip protrusion was compared
      with the impact of a Hill-type muscle model. RESULTS: The force-length
      characteristic associated with the muscle elements matched well with the
      invariant characteristics of the lambda model. The impact of the passive
      properties was assessed. Isometric force variation and isotonic displacements
      were modeled. The comparison with a Hill-type model revealed strong similarities
      in terms of global stress and strain. CONCLUSION: The DLM accounted for the
      characteristics of the lambda model. Biomechanically, no clear differences were
      found between the DLM and a Hill-type model. Accurate evaluations of the lambda
      model, based on the comparison between data and simulations, are now possible
      with 3-D biomechanical descriptions of the speech articulators because of the
      DLM.

PMID- 24687447
TI  - Interspeaker variability in hard palate morphology and vowel production.
AB  - PURPOSE: Differences in vocal tract morphology have the potential to explain
      interspeaker variability in speech production. The potential acoustic impact of
      hard palate shape was examined in simulation, in addition to the interplay among
      morphology, articulation, and acoustics in real vowel production data. METHOD:
      High-front vowel production from 5 speakers of American English was examined
      using midsagittal real-time magnetic resonance imaging data with synchronized
      audio. Relationships among hard palate morphology, tongue shaping, and formant
      frequencies were analyzed. Simulations were performed to determine the acoustical
      properties of vocal tracts whose area functions are altered according to
      prominent hard palate variations. RESULTS: Simulations revealed that altering the
      height and position of the palatal dome alters formant frequencies. Examinations
      of real speech data showed that palatal morphology is not significantly
      correlated with any formant frequency but is correlated with major aspects of
      lingual articulation. CONCLUSION: Certain differences in hard palate morphology
      can substantially affect vowel acoustics, but those effects are not noticeable in
      real speech. Speakers adapt their lingual articulation to accommodate palate
      shape differences with the potential to substantially affect formant frequencies,
      while ignoring palate shape differences with relatively little acoustic impact,
      lending support for acoustic goals of vowel production.

PMID- 24687448
TI  - Toll-like receptors, immunoproteasome and regulatory T cells in children with
      Henoch-Schonlein purpura and primary IgA nephropathy.
AB  - BACKGROUND: Henoch-Schonlein purpura (HSP) nephritis and primary IgA nephropathy
      (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical
      features. The suspected involvement of different immune system pathways is
      largely unknown. METHODS: This study was aimed at investigating some of the
      immunological features including Toll-like receptors (TLR), proteasome
      (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17
      cells) in 63 children with HSP with/without renal involvement and in 25 with
      pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral
      blood mononuclear cells (PBMC). RESULTS: The expression of mRNAs encoding for
      TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases
      FoxP3mRNA and TGF-beta1mRNA expression was significantly lower than in HC. A
      switch from PS to iPS (LMP2/beta1) was detected only in PBMC of HSP and it
      correlated with the level of TLR2mRNA, which was selectively increased only in
      children with HSP. CONCLUSION: Children with HSP and pIgAN present with similar
      signs of engagement of the innate immunity and regulatory T cell depression. The
      increased immunoproteasome switch, which correlated with TLR2 activation, may
      suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This
      research area also deserves further investigation for possible therapeutic
      applications.

PMID- 24687449
TI  - Explaining health inequalities: the role of space and time.

PMID- 24687450
TI  - Human-animal relationships in zoo-housed orangutans (P. abelii) and gorillas (G.
      g. gorilla): the effects of familiarity.
AB  - I examined human-animal relationships (HARs) in zoo-housed orangutans (Pongo
      abelii) and gorillas (Gorilla gorilla gorilla) to see if they followed patterns
      similar to conspecific relationships in great apes and humans. Familiarity and
      social relationships guide humans' and great apes' behaviors with conspecifics.
      Inter-individual relationships, based on shared social history, and "generalized"
      relationships, based on a history of interactions with relevant classes of
      individuals, guide behavior with familiar and unfamiliar conspecifics,
      respectively. I examined whether both familiarity and social relationships
      similarly guides great apes' cross-species interactions with humans. I used
      repeated measures MANOVA to compare hourly rates and average durations of ape
      initiated human-directed behaviors (HDBs) between familiar and unfamiliar humans
      and between great ape species. HDB patterns were consistent with familiarity
      based HAR predictions, indicating more negative relationships with unfamiliar
      humans and more positive relationships with familiar humans. Findings for
      unfamiliar humans are consistent with negative effects of humans on apes'
      behavior reported in traditional visitor effect studies (VES). However, findings
      for familiar humans may be overlooked in VES due to pooling across levels of
      human familiarity or failure to consider humans other than primarily unfamiliar
      visitors. Additionally, species differences in apes' HDBs suggest that data
      pooling across species, common in many zoo studies, may mask important
      differences. These findings have important methodological implications for
      studies of human-animal interaction as well as for captive animal wellbeing.

PMID- 24687452
TI  - Colloidal RBC-shaped, hydrophilic, and hollow mesoporous carbon nanocapsules for
      highly efficient biomedical engineering.

PMID- 24687453
TI  - Staphylococcus epidermidis adhesion on hydrophobic and hydrophilic textured
      biomaterial surfaces.
AB  - It is of great interest to use nano- or micro-structured surfaces to inhibit
      microbial adhesion and biofilm formation and thereby to prevent biomaterial
      associated infection, without modification of the surface chemistry or bulk
      properties of the materials and without use of the drugs. Our previous study
      showed that a submicron textured polyurethane surface can inhibit staphylococcal
      bacterial adhesion and biofilm formation. To further understand the effect of the
      geometry of textures on bacterial adhesion as well as the underlying mechanism,
      in this study, submicron and micron textured polyurethane surfaces featuring
      ordered arrays of pillars were fabricated and modified to have different
      wettabilities. All the textured surfaces were originally hydrophobic and showed
      significant reductions in Staphylococcus epidermidis RP62A adhesion in phosphate
      buffered saline or 25% platelet poor plasma solutions under shear, as compared to
      smooth surfaces. After being subjected to an air glow discharge plasma treatment,
      all polyurethane surfaces were modified to hydrophilic, and reductions in
      bacterial adhesion on surfaces were subsequently found to be dependent on the
      size of the patterns. The submicron patterned surfaces reduced bacterial
      adhesion, while the micron patterned surfaces led to increased bacterial
      adhesion. The extracellular polymeric substances (EPS) from the S. epidermidis
      cell surfaces were extracted and purified, and were coated on a glass colloidal
      surface so that the adhesion force and separation energy in interactions of the
      EPS and the surface could be measured by colloidal probe atomic force microscopy.
      These results were consistent with the bacterial adhesion observations. Overall,
      the data suggest that the increased surface hydrophobicity and the decreased
      availability of the contact area contributes to a reduction in bacterial adhesion
      to the hydrophobic textured surfaces, while the availability of the contact area
      is the primary determinant factor for bacterial adhesion on hydrophilic textured
      surfaces. 

PMID- 24687451
TI  - Recent advances in enrichment and separation strategies for mass spectrometry
      based phosphoproteomics.
AB  - Due to the significance of protein phosphorylation in various biological
      processes and signaling events, new analytical techniques for enhanced
      phosphoproteomics have been rapidly introduced in the recent years. The
      combinatorial use of the phospho-specific enrichment techniques and
      prefractionation methods prior to MS analysis enable comprehensive profiling of
      the phosphoproteome and facilitate deciphering the critical roles that
      phosphorylation plays in signaling pathways in various biological systems. This
      review places special emphasis on the recent five-year (2009-2013) advances for
      enrichment and separation techniques that have been utilized for phosphopeptides
      prior to MS analysis. 

PMID- 24687454
TI  - Development of a clinical chemiluminescent immunoassay for serum GPC3 and
      simultaneous measurements alone with AFP and CK19 in diagnosis of hepatocellular
      carcinoma.
AB  - BACKGROUND: Glypican-3 (GPC3) is an oncofetal antigen that shows great promise as
      a biomarker for diagnosis of hepatocellular carcinoma (HCC), but there is no
      reliable kit that can be used to detect it in clinics. The aim of this study is
      to develop a stable performance kit for GPC3 detection in clinics. DESIGN AND
      METHODS: The paired antibodies were identified through cycle-screening methods
      based on our previous research. Then, a double antibodies sandwich
      chemiluminescent immunoassay for detecting serum GPC3 was developed. The
      performance of the developed GPC3 diagnostic kit was evaluated by detecting the
      concentration of serum GPC3 and assessing its single or combined use with alpha
      fetoprotein (AFP) and cytokeratin 19 fragment (CK19) for HCC diagnosis. RESULTS:
      The assay demonstrated a linear range of 10-800 ng/ml, the cross-reactivity rate
      at 0.018% (AFP), 0.020% (carcino-embryonic antigen), and 0.021% (CK19),
      respectively. The minimum detectable concentration was 0.05 ng/ml; the intraassay
      coefficient of variation (CV) and interassay CV were both less than 10%, with
      good stability and reproducibility. GPC3 has a high sensitivity (54.2%) and
      specificity (99.4%) in diagnosing HCC. The level of GPC3 in HCC was robust higher
      than that in healthy or other liver diseases' sera (108.67 +/- 230.04 ng/ml vs.
      3.99 +/- 7.68 ng/ml). The diagnostic sensitivity of GPC3 single or combined with
      CK19 and AFP for HCC was evaluated, and the rates were 54.2 and 90.6%,
      respectively. CONCLUSIONS: An applicable chemiluminescent immunoassay with stable
      performance against GPC3 in diagnosing HCC has been established and the
      combination of GPC3 with CK19 and AFP could improve the diagnostic sensitivity
      for HCC.

PMID- 24687456
TI  - Ebola outbreak claims more than 60 lives.

PMID- 24687455
TI  - Simvastatin treatment enhances NMDAR-mediated synaptic transmission by
      upregulating the surface distribution of the GluN2B subunit.
AB  - The ramifications of statins on plasma cholesterol and coronary heart disease
      have been well documented. However, there is increasing evidence that inhibition
      of the mevalonate pathway may provide independent neuroprotective and
      procognitive pleiotropic effects, most likely via inhibition of isoprenoids,
      mainly farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). FPP
      and GGPP are the major donors of prenyl groups for protein prenylation.
      Modulation of isoprenoid availability impacts a slew of cellular processes
      including synaptic plasticity in the hippocampus. Our previous work has
      demonstrated that simvastatin (SV) administration improves hippocampus-dependent
      spatial memory, rescuing memory deficits in a mouse model of Alzheimer's disease.
      Treatment of hippocampal slices with SV enhances long-term potentiation (LTP),
      and this effect is dependent on the activation of Akt (protein kinase B). Further
      studies showed that SV-induced enhancement of hippocampal LTP is driven by
      depletion of FPP and inhibition of farnesylation. In the present study, we report
      the functional consequences of exposure to SV at cellular/synaptic and molecular
      levels. While application of SV has no effect on intrinsic membrane properties of
      CA1 pyramidal neurons, including hyperpolarization-activated cyclic-nucleotide
      channel-mediated sag potentials, the afterhyperpolarization (AHP), and
      excitability, SV application potentiates the N-methyl D-aspartate receptor
      (NMDAR)-mediated contribution to synaptic transmission. In mouse hippocampal
      slices and human neuronal cells, SV treatment increases the surface distribution
      of the GluN2B subunit of the NMDAR without affecting cellular cholesterol
      content. We conclude that SV-induced enhancement of synaptic plasticity in the
      hippocampus is likely mediated by augmentation of synaptic NMDAR components that
      are largely responsible for driving synaptic plasticity in the CA1 region.

PMID- 24687458
TI  - Distributed MRI reconstruction using Gadgetron-based cloud computing.
AB  - PURPOSE: To expand the open source Gadgetron reconstruction framework to support
      distributed computing and to demonstrate that a multinode version of the
      Gadgetron can be used to provide nonlinear reconstruction with clinically
      acceptable latency. METHODS: The Gadgetron framework was extended with new
      software components that enable an arbitrary number of Gadgetron instances to
      collaborate on a reconstruction task. This cloud-enabled version of the Gadgetron
      was deployed on three different distributed computing platforms ranging from a
      heterogeneous collection of commodity computers to the commercial Amazon Elastic
      Compute Cloud. The Gadgetron cloud was used to provide nonlinear, compressed
      sensing reconstruction on a clinical scanner with low reconstruction latency (eg,
      cardiac and neuroimaging applications). RESULTS: The proposed setup was able to
      handle acquisition and 11 -SPIRiT reconstruction of nine high temporal resolution
      real-time, cardiac short axis cine acquisitions, covering the ventricles for
      functional evaluation, in under 1 min. A three-dimensional high-resolution brain
      acquisition with 1 mm(3) isotropic pixel size was acquired and reconstructed with
      nonlinear reconstruction in less than 5 min. CONCLUSION: A distributed computing
      enabled Gadgetron provides a scalable way to improve reconstruction performance
      using commodity cluster computing. Nonlinear, compressed sensing reconstruction
      can be deployed clinically with low image reconstruction latency.

PMID- 24687457
TI  - Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral
      neuropathy.
AB  - BACKGROUND: Peroxynitrite, a product of the reaction of superoxide with nitric
      oxide, causes oxidative stress with concomitant inactivation of enzymes, poly(ADP
      ribosylation), mitochondrial dysfunction and impaired stress signalling, as well
      as protein nitration. In this study, we sought to determine the effect of
      preventing protein nitration or increasing peroxynitrite decomposition on
      diabetic neuropathy in mice after an extended period of untreated diabetes.
      METHODS: C57Bl6/J male control and diabetic mice were treated with the
      peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate
      (FeTMPS, 10 mg/kg/day) or protein nitration inhibitor (-)-epicatechin gallate (20
      mg/kg/day) for 4 weeks, after an initial 28 weeks of hyperglycaemia. RESULTS:
      Untreated diabetic mice developed motor and sensory nerve conduction velocity
      deficits, thermal and mechanical hypoalgesia, tactile allodynia and loss of
      intraepidermal nerve fibres. Both FeTMPS and epicatechin gallate partially
      corrected sensory nerve conduction slowing and small sensory nerve fibre
      dysfunction without alleviation of hyperglycaemia. Correction of motor nerve
      conduction deficit and increase in intraepidermal nerve fibre density were found
      with FeTMPS treatment only. CONCLUSIONS: Peroxynitrite injury and protein
      nitration are implicated in the development of diabetic peripheral neuropathy.
      The findings indicate that both structural and functional changes of chronic
      diabetic peripheral neuropathy can be reversed and provide rationale for the
      development of a new generation of antioxidants and peroxynitrite decomposition
      catalysts for treatment of diabetic peripheral neuropathy.

PMID- 24687459
TI  - Comparative changes in the antioxidant system in the flag leaf of early and
      normally senescing near-isogenic lines of wheat (Triticum aestivum L.).
AB  - KEY MESSAGE: The antioxidant system was significantly inhibited in the early
      aging line than the near-isogenic normal aging line during senescence. The
      antioxidant system plays pivotal roles in removal of reactive oxygen species
      (ROS) produced during leaf senescence. To explore its roles in leaf senescence of
      wheat (Triticum aestivum L.), the concentrations of antioxidants, activities, and
      gene expression of antioxidant enzymes were evaluated in flag leaves of the early
      aging line (EAL) and the near-isogenic normal aging line (NL) during senescence.
      The results showed that the total chlorophyll and soluble protein in the EAL
      declined earlier and faster, while more malondialdehyde and ROS accumulated
      compared with the NL. The activities of superoxide dismutase, catalase, ascorbate
      peroxidase, dehydroascorbate reductase, and glutathione reductase were lower in
      the EAL than in the NL across multiple measuring dates. Additionally, the EAL had
      less amounts of reduced ascorbate and glutathione as well as lower reduction
      state with the progression of senescence. Concomitantly, the gene expression of
      antioxidant enzymes in the EAL was also significantly repressed relative to those
      in the NL during natural senescence. Taken together, the earlier onset and faster
      rate of senescence in the EAL could be a result of an imbalance of ROS production
      and ROS-scavenging antioxidant system, which provided valuable hints toward
      understanding leaf senescence of wheat.

PMID- 24687460
TI  - Teeth clenching reduces arm abduction force.
AB  - It has been reported that the 90 degrees  arm abduction force counteracting
      external adduction loads appeared to be smaller under teeth clenching condition
      than under non-clenching condition. To elucidate the physiological mechanism
      underlying the possible inhibitory effect of teeth clenching on the arm
      abduction, we have attempted to quantify the difference in the force induced
      against the fast and slow ramp load between the arm abductions under teeth non
      clenching and clenching conditions. When the load of adduction moment was
      linearly increased, the abductor force increased to a maximal isometric
      contraction force (MICF) and further increased to a maximal eccentric contraction
      force (MECF) with forced adduction. The MICF measured under teeth clenching was
      significantly lower than that under non-clenching, despite no significant
      difference in the MECF between the two conditions. The reduction in MICF caused
      by teeth clenching was enhanced by increasing the velocity of the load. These
      results suggest that clenching inhibits abduction force only during isometric
      contraction phase. The invariability of MECF would indicate the lack of
      involvement of fatigue in such inhibitory effects of clenching. To discover the
      source of the inhibition, we have examined the effects of teeth clenching on the
      stretch reflex in the deltoid muscle. The stretch reflex of deltoid muscles was
      inhibited during clenching, contrary to what was expected from the Jendrassik
      maneuver. Taken together, our results suggest that the teeth clenching reduced
      the MICF by depressing the recruitment of deltoid motoneurones presumably via the
      presynaptic inhibition of spindle afferent inputs onto those motoneurones.

PMID- 24687461
TI  - Drive for activity in patients with anorexia nervosa.
AB  - OBJECTIVE: Hyperactivity and elevated physical activity are both considered
      symptom characteristics of anorexia nervosa (AN). It has been suggested that a
      drive for activity (DFA) may underlie these expressions, yet research into DFA in
      AN remains scant. This study investigated DFA levels in patients with AN and its
      relation to AN severity. Furthermore, as physical exercise may be a way to reduce
      negative affect, the influence of negative affect (anxiety) on the role of DFA in
      AN was tested. METHOD: Two hundred and forty female patients with AN completed
      measures for DFA, eating disorder (ED) pathology, anxiety, and clinical
      parameters. RESULTS: A strong relation between DFA levels and ED pathology was
      found, which remained significant even after controlling for negative affect
      (anxiety). DISCUSSION: After much theorizing about DFA in AN this study provides
      empirical evidence for DFA as a hallmark feature of AN, independent of anxiety
      levels. Future research should shed light on the relationships between DFA,
      actual physical activity, and the course of AN.

PMID- 24687462
TI  - Atypical femoral fractures in association with bisphosphonate therapy: a case
      series.
AB  - Well-established clinically as frontline therapy in the management of
      osteoporosis, bisphosphonates have been shown in numerous trials to be highly
      effective in reducing the risk of both vertebral and hip fractures. More
      recently, however, in a multitude of exhaustive case reviews, attention has been
      raised to the small but by now well-established link between prolonged
      bisphosphonate usage and the risk for atypical subtrochanteric femoral stress
      fractures. We present herein a trio of illustrative cases highlighting both
      clinical presentation and characteristic radiological findings thereof, as well
      as a discussion of the background, management, and natural history of these
      oftentimes problematic injuries. 

PMID- 24687464
TI  - A longitudinal study of very young children's vowel production.
AB  - PURPOSE: Ecologically realistic, spontaneous, adult-directed, longitudinal speech
      data of young children were described by acoustic analyses. METHOD: The first 2
      formant frequencies of vowels produced by 6 children from different American
      English dialect regions were analyzed from ages 18 to 48 months. The vowels were
      from largely conversational contexts and were classified according to dictionary
      pronunciation. RESULTS: Within-subject formant frequency variability remained
      relatively constant for the span of ages studied. It was often difficult to
      detect overall decreases in the first 2 formant frequencies between ages 30 and
      48 months. A study of the movement of the corner vowels with respect to the vowel
      centroid showed that the shape of the vowel space remained qualitatively constant
      from 30 through 48 months. CONCLUSIONS: The shape of the vowel space is
      established early in life. Some aspects of regional dialect were observed in some
      of the subjects at 42 months of age. The present study adds to the existing data
      on the development of vowel spaces by describing ecologically realistic speech.

PMID- 24687465
TI  - Quantitative and descriptive comparison of four acoustic analysis systems: vowel
      measurements.
AB  - PURPOSE: This study examines accuracy and comparability of 4 trademarked acoustic
      analysis software packages (AASPs): Praat, WaveSurfer, TF32, and CSL by using
      synthesized and natural vowels. Features of AASPs are also described. METHOD:
      Synthesized and natural vowels were analyzed using each of the AASP's default
      settings to secure 9 acoustic measures: fundamental frequency (F0), formant
      frequencies (F1-F4), and formant bandwidths (B1-B4). The discrepancy between the
      software measured values and the input values (synthesized, previously reported,
      and manual measurements) was used to assess comparability and accuracy. Basic
      AASP features are described. RESULTS: Results indicate that Praat, WaveSurfer,
      and TF32 generate accurate and comparable F0 and F1-F4 data for synthesized
      vowels and adult male natural vowels. Results varied by vowel for women and
      children, with some serious errors. Bandwidth measurements by AASPs were highly
      inaccurate as compared with manual measurements and published data on formant
      bandwidths. CONCLUSIONS: Values of F0 and F1-F4 are generally consistent and
      fairly accurate for adult vowels and for some child vowels using the default
      settings in Praat, WaveSurfer, and TF32. Manipulation of default settings yields
      improved output values in TF32 and CSL. Caution is recommended especially before
      accepting F1-F4 results for children and B1-B4 results for all speakers.

PMID- 24687466
TI  - Influence of the perceived taste intensity of chemesthetic stimuli on swallowing
      parameters given age and genetic taste differences in healthy adult women.
AB  - PURPOSE: This study examined whether the perceived taste intensity of liquids
      with chemesthetic properties influenced lingua-palatal pressures and submental
      surface electromyography (sEMG) in swallowing, compared with water. METHOD:
      Swallowing was studied in 80 healthy women, stratified by age group and genetic
      taste status. General Labeled Magnitude Scale ratings of taste intensity were
      collected for deionized water; carbonated water; 2.7% w/v citric acid; and
      diluted ethanol. These stimuli were swallowed, with measurement of tongue-palate
      pressures and submental sEMG. Path analysis differentiated stimulus, genetic
      taste status, age, and perceived taste intensity effects on swallowing. Signal
      amplitude during effortful saliva swallowing served as a covariate representing
      participant strength. RESULTS: Significant differences (p < .05) in taste
      intensity were seen across liquids: citric acid > ethanol > carbonated water >
      water. Supertasters perceived greater taste intensity than did nontasters. Lingua
      palatal pressure and sEMG amplitudes were correlated with the strength covariate.
      Anterior palate pressures and sEMG amplitudes were significantly higher for the
      citric acid stimulus. Perceived taste intensity was a significant mediator of
      stimulus differences. CONCLUSION: These data provide confirmatory evidence that
      high-intensity sour stimuli do influence swallowing behaviors. In addition, taste
      genetics influence the perception of taste intensity for stimuli with
      chemesthetic properties, which modulates behavioral responses.

PMID- 24687467
TI  - Vowel acoustics in dysarthria: speech disorder diagnosis and classification.
AB  - PURPOSE: The purpose of this study was to determine the extent to which vowel
      metrics are capable of distinguishing healthy from dysarthric speech and among
      different forms of dysarthria. METHOD: A variety of vowel metrics were derived
      from spectral and temporal measurements of vowel tokens embedded in phrases
      produced by 45 speakers with dysarthria and 12 speakers with no history of
      neurological disease. Via means testing and discriminant function analysis (DFA),
      the acoustic metrics were used to (a) detect the presence of dysarthria and (b)
      classify the dysarthria subtype. RESULTS: Significant differences between
      dysarthric and healthy control speakers were revealed for all vowel metrics.
      However, the results of the DFA demonstrated some metrics (particularly metrics
      that capture vowel distinctiveness) to be more sensitive and specific predictors
      of dysarthria. Only the vowel metrics that captured slope of the second formant
      (F2) demonstrated between-group differences across the dysarthrias. However, when
      subjected to DFA, these metrics proved unreliable classifiers of dysarthria
      subtype. CONCLUSION: The results of these analyses suggest that some vowel
      metrics may be useful clinically for the detection of dysarthria but may not be
      reliable indicators of dysarthria subtype using the current dysarthria
      classification scheme.

PMID- 24687468
TI  - Vowel acoustics in dysarthria: mapping to perception.
AB  - PURPOSE: The aim of the present report was to explore whether vowel metrics,
      demonstrated to distinguish dysarthric and healthy speech in a companion article
      (Lansford & Liss, 2014), are able to predict human perceptual performance.
      METHOD: Vowel metrics derived from vowels embedded in phrases produced by 45
      speakers with dysarthria were compared with orthographic transcriptions of these
      phrases collected from 120 healthy listeners. First, correlation and stepwise
      multiple regressions were conducted to identify acoustic metrics that had
      predictive value for perceptual measures. Next, discriminant function analysis
      misclassifications were compared with listeners' misperceptions to examine more
      directly the perceptual consequences of degraded vowel acoustics. RESULTS:
      Several moderate correlative relationships were found between acoustic metrics
      and perceptual measures, with predictive models accounting for 18%-75% of the
      variance in measures of intelligibility and vowel accuracy. Results of the second
      analysis showed that listeners better identified acoustically distinctive vowel
      tokens. In addition, the level of agreement between misclassified-to-misperceived
      vowel tokens supports some specificity of degraded acoustic profiles on the
      resulting percept. CONCLUSION: Results provide evidence that degraded vowel
      acoustics have some effect on human perceptual performance, even in the presence
      of extravowel variables that naturally exert influence in phrase perception.

PMID- 24687469
TI  - Quantitative assessment of interutterance stability: application to dysarthria.
AB  - PURPOSE: Following recent attempts to quantify articulatory impairment in speech,
      the present study evaluates the usefulness of a novel measure of motor stability
      to characterize dysarthria. METHOD: The study included 8 speakers with ataxic
      dysarthria (AD), 16 speakers with hypokinetic dysarthria (HD) as a result of
      Parkinson's disease, and 24 unimpaired control participants. Each participant
      performed a series of sentence repetitions under habitual, fast, and slow
      speaking rate conditions. An algorithm to measure utterance-to-utterance spectro
      temporal variation (UUV; Cummins, 2009) was used. Speech rate and intelligibility
      were also measured. RESULTS: UUV scores were significantly correlated with
      perceptually based intelligibility scores. There were significant differences in
      UUV between control speakers and the AD but not the HD groups, presumably because
      of differences in intelligibility in the samples used and not because of
      differences in pathology. Habitual speaking rate did not correlate with UUV
      scores. All speaker groups had greater UUV levels in the slow conditions compared
      with habitual and fast speaking rates. CONCLUSIONS: UUV results were consistent
      with those of other variability indices and thus appear to capture motor control
      issues in a similar way. The results suggest that the UUV could be developed into
      an easy-to-use clinical tool that could function as a valid and reliable
      assessment and outcome measure.

PMID- 24687470
TI  - A differential item functioning (DIF) analysis of the Communicative Participation
      Item Bank (CPIB): comparing individuals with Parkinson's disease from the United
      States and New Zealand.
AB  - PURPOSE: To examine the cross-cultural applicability of the Communicative
      Participation Item Bank (CPIB) through a comparison of respondents with
      Parkinson's disease (PD) from the United States and New Zealand. METHOD: A total
      of 428 respondents-218 from the United States and 210 from New Zealand-completed
      the self-report CPIB and a series of demographic questions. Differential item
      functioning (DIF) analyses were conducted to examine whether response bias was
      present across the 2 groups. RESULTS: No items were identified as having
      statistically significant DIF across the U.S. and N.Z. cohorts. CONCLUSION: The
      current CPIB items and scoring parameters are also suitable for use with
      respondents from New Zealand.

PMID- 24687472
TI  - Evaluating the dimensionality of first-grade written composition.
AB  - PURPOSE: This study examined dimensions of written composition by using multiple
      evaluative approaches such as an adapted 6 + 1 trait scoring, syntactic
      complexity measures, and productivity measures. It further examined unique
      relations of oral language and literacy skills to the identified dimensions of
      written composition. METHOD: A large sample of 1st-grade students (N = 527) was
      assessed on their language, reading, spelling, letter writing automaticity, and
      writing in the spring. Data were analyzed using a latent variable approach,
      including confirmatory factor analysis and structural equation modeling. RESULTS:
      The seven traits in the 6 + 1 trait system were best described as two constructs:
      substantive quality and spelling and writing conventions. When the other
      evaluation procedures such as productivity and syntactic complexity indicators
      were included, four dimensions emerged: substantive quality, productivity,
      syntactic complexity, and spelling and writing conventions. Language and literacy
      predictors were differentially related to each dimension in written composition.
      CONCLUSION: These four dimensions may be a useful guideline for evaluating
      developing beginning writers' compositions.

PMID- 24687473
TI  - An investigation into semantic and phonological processing in individuals with
      Williams syndrome.
AB  - PURPOSE: The current study examined semantic and phonological processing in
      individuals with Williams syndrome (WS). Previous research in language processing
      in individuals with WS suggests a complex linguistic system characterized by
      "deviant" semantic organization and differential phonological processing. METHOD:
      Two experiments explored these representations in individuals with WS. The first
      experiment analyzed the relative typicality and frequency of participants'
      responses to a semantic and phonological fluency task. The second experiment
      tapped into online language processing through a semantic priming task and an
      online sentence reading task measuring the effects of word frequency. Thirteen
      participants with WS were matched to a group of participants on reading grade
      level and a group of participants on chronological age. RESULTS: The results of
      the semantic fluency task, semantic priming task, and word frequency task suggest
      that semantic organization in individuals with WS appears commensurate with their
      reading level rather than deviant. CONCLUSIONS: The pattern of results suggests
      that individuals with WS do not appear to have deviant semantic organization,
      while confirming that online tasks that tap into these processes are a promising
      direction in investigations that include atypically developing populations. These
      findings for the phonological tasks warrant further research into phonological
      processing in individuals with WS.

PMID- 24687474
TI  - Detection of lexical and morphological anomalies by children with and without
      language impairment.
AB  - PURPOSE: The abilities of 5-year-old children with and without language
      impairment (LI) to detect anomalies involving lexical items and grammatical
      morphemes in stories were compared. The influence of sentence versus discourse
      context on lexical anomaly detection rates was explored. METHOD: The participants
      were read 3 story scripts and asked to detect the anomalies embedded in them.
      RESULTS: Typically developing (TD) children outperformed their peers with LI
      across the board. For both groups, lexical anomalies were easier to detect than
      morphological anomalies. Similarly, anomalous nouns were easier for both groups
      to detect compared with anomalous verbs. The latter presented a particular
      challenge to the children with LI. Both groups had greater difficulty with
      lexical anomaly detection in discourse relative to sentence context. CONCLUSION:
      These outcomes suggest that children's ability to detect anomalies is sensitive
      to the nature of the anomaly and the linguistic context involved in anomaly
      detection. Future research may address the relative role of linguistic and
      cognitive factors in anomaly detection.

PMID- 24687471
TI  - Genome-wide association study of receptive language ability of 12-year-olds.
AB  - PURPOSE: Researchers have previously shown that individual differences in
      measures of receptive language ability at age 12 are highly heritable. In the
      current study, the authors attempted to identify some of the genes responsible
      for the heritability of receptive language ability using a genome-wide
      association approach. METHOD: The authors administered 4 Internet-based measures
      of receptive language (vocabulary, semantics, syntax, and pragmatics) to a sample
      of 2,329 twelve-year-olds for whom DNA and genome-wide genotyping were available.
      Nearly 700,000 single-nucleotide polymorphisms (SNPs) and 1 million imputed SNPs
      were included in a genome-wide association analysis of receptive language
      composite scores. RESULTS: No SNP associations met the demanding criterion of
      genome-wide significance that corrects for multiple testing across the genome ( p
      < 5 * 10 -8). The strongest SNP association did not replicate in an additional
      sample of 2,639 twelve-year-olds. CONCLUSIONS: These results indicate that
      individual differences in receptive language ability in the general population do
      not reflect common genetic variants that account for more than 3% of the
      phenotypic variance. The search for genetic variants associated with language
      skill will require larger samples and additional methods to identify and
      functionally characterize the full spectrum of risk variants.

PMID- 24687475
TI  - Large-corpus phoneme and word recognition and the generality of lexical context
      in CVC word perception.
AB  - PURPOSE: Speech recognition may be analyzed in terms of recognition probabilities
      for perceptual wholes (e.g., words) and parts (e.g., phonemes), where j or the j
      factor reveals the number of independent perceptual units required for
      recognition of the whole (Boothroyd, 1968b; Boothroyd & Nittrouer, 1988;
      Nittrouer & Boothroyd, 1990). For consonant-vowel-consonant (CVC) nonsense
      syllables, j ~ 3 because all 3 phonemes are needed to identify the syllable, but
      j ~ 2.5 for real-word CVCs (revealing ~2.5 independent perceptual units) because
      higher level contributions such as lexical knowledge enable word recognition even
      if less than 3 phonemes are accurately received. These findings were almost
      exclusively determined with the 120-word corpus of the isophonemic word lists
      (Boothroyd, 1968a; Boothroyd & Nittrouer, 1988), presented one word at a time. It
      is therefore possible that its generality or applicability may be limited. This
      study thus determined j by using a much larger and less restricted corpus of real
      word CVCs presented in 3-word groups as well as whether j is influenced by test
      size. METHOD: The j-factor for real-word CVCs was derived from the recognition
      performance of 223 individuals with a broad range of hearing sensitivity by using
      the Tri-Word Test (Gelfand, 1998), which involves 50 three-word presentations and
      a corpus of 450 words. The influence of test size was determined from a subsample
      of 96 participants with separate scores for the first 10, 20, and 25 (and all 50)
      presentation sets of the full test. RESULTS: The mean value of j was 2.48 with a
      95% confidence interval of 2.44-2.53, which is in good agreement with values
      obtained with isophonemic word lists, although its value varies among
      individuals. A significant correlation was found between percent-correct scores
      and j, but it was small and accounted for only 12.4% of the variance in j for
      phoneme scores >=60%. Mean j-factors for the 10-, 20-, 25-, and 50-set test sizes
      were between 2.49 and 2.53 and were not significantly different from one another.
      CONCLUSIONS: The j-factor based on a 450-word corpus and tri-word testing
      confirms and expands on findings from single-word presentations of isophonemic
      lists and a 120-word corpus. This enhances the generality (external validity) of
      the notions that j ~ 2.5 for real-word CVCs, and lexical knowledge enables CVC
      word recognition based on ~2.5 independent perceptual units. The robust nature of
      isophonemic word test outcomes is confirmed by close agreement with those
      provided by the high-reliability Tri-Word Test. Percent-correct performance was
      correlated with j but appeared to account for less than 13% of j-factor variance
      for most scores likely to be encountered in practice. Variability in the size of
      j suggests individual differences in the ability to take advantage of lexical
      knowledge in word recognition. The j-factor may be useful to inform
      rehabilitation needs, intervention content, and outcome assessment, as well as
      for other clinical applications.

PMID- 24687476
TI  - Children's perception of speech produced in a two-talker background.
AB  - PURPOSE: This study evaluated the degree to which children benefit from the
      acoustic modifications made by talkers when they produce speech in noise. METHOD:
      A repeated measures design compared the speech perception performance of children
      (5-11 years) and adults in a 2-talker masker. Target speech was produced in a 2
      talker background or in quiet. In Experiment 1, recognition with the 2 target
      sets was assessed using an adaptive spondee identification procedure. In
      Experiment 2, the benefit of speech produced in a 2-talker background was
      assessed using an open-set, monosyllabic word recognition task at a fixed signal
      to-noise ratio (SNR). RESULTS: Children performed more poorly than adults,
      regardless of whether the target speech was produced in quiet or in a 2-talker
      background. A small improvement in the SNR required to identify spondees was
      observed for both children and adults using speech produced in a 2-talker
      background (Experiment 1). Similarly, average open-set word recognition scores
      were 11 percentage points higher for both age groups using speech produced in a 2
      talker background compared with quiet (Experiment 2). CONCLUSION: The results
      indicate that children can use the acoustic modifications of speech produced in a
      2-talker background to improve masked speech perception, as previously
      demonstrated for adults.

PMID- 24687477
TI  - The lymphatic pathway for microbubbles.

PMID- 24687478
TI  - Ultrasonic detection of decompression-induced bubbles.

PMID- 24687479
TI  - The use of portable 2D echocardiography and 'frame-based' bubble counting as a
      tool to evaluate diving decompression stress.
AB  - INTRODUCTION: 'Decompression stress' is commonly evaluated by scoring circulating
      bubble numbers post dive using Doppler or cardiac echography. This information
      may be used to develop safer decompression algorithms, assuming that the lower
      the numbers of venous gas emboli (VGE) observed post dive, the lower the
      statistical risk of decompression sickness (DCS). Current echocardiographic
      evaluation of VGE, using the Eftedal and Brubakk method, has some disadvantages
      as it is less well suited for large-scale evaluation of recreational diving
      profiles. We propose and validate a new 'frame-based' VGE-counting method which
      offers a continuous scale of measurement. METHODS: Nine 'raters' of varying
      familiarity with echocardiography were asked to grade 20 echocardiograph
      recordings using both the Eftedal and Brubakk grading and the new 'frame-based'
      counting method. They were also asked to count the number of bubbles in 50 still
      frame images, some of which were randomly repeated. A Wilcoxon Spearman rho
      calculation was used to assess test-retest reliability of each rater for the
      repeated still frames. For the video images, weighted kappa statistics, with
      linear and quadratic weightings, were calculated to measure agreement between
      raters for the Eftedal and Brubakk method. Bland-Altman plots and intra-class
      correlation coefficients were used to measure agreement between raters for the
      frame-based counting method. RESULTS: Frame-based counting showed a better inter
      rater agreement than the Eftedal and Brubakk grading, even with relatively
      inexperienced assessors, and has good intra- and inter-rater reliability.
      CONCLUSION: Frame-based bubble counting could be used to evaluate post-dive
      decompression stress, and offers possibilities for computer-automated algorithms
      to allow near-real-time counting.

PMID- 24687480
TI  - Sample size requirement for comparison of decompression outcomes using
      ultrasonically detected venous gas emboli (VGE): power calculations using Monte
      Carlo resampling from real data.
AB  - INTRODUCTION: In studies of decompression procedures, ultrasonically detected
      venous gas emboli (VGE) are commonly used as a surrogate outcome if decompression
      sickness (DCS) is unlikely to be observed. There is substantial variability in
      observed VGE grades, and studies should be designed with sufficient power to
      detect an important effect. METHODS: Data for estimating sample size requirements
      for studies using VGE as an outcome is provided by a comparison of two
      decompression schedules that found corresponding differences in DCS incidence
      (3/192 [DCS/dives] vs. 10/198) and median maximum VGE grade (2 vs. 3, P < 0.0001,
      Wilcoxon test). Sixty-two subjects dived each schedule at least once, accounting
      for 183 and 180 man-dives on each schedule. From these data, the frequency with
      which 10,000 randomly resampled, paired samples of maximum VGE grade were
      significantly different (paired Wilcoxon test, one-sided P ? 0.05 or 0.025) in
      the same direction as the VGE grades of the full data set were counted (estimated
      power). Resampling was also used to estimate power of a Bayesian method that
      ranks two samples based on DCS risks estimated from the VGE grades. RESULTS:
      Paired sample sizes of 50 subjects yielded about 80% power, but the power dropped
      to less than 50% with fewer than 30 subjects. CONCLUSIONS: Comparisons of VGE
      grades that fail to find a difference between paired sample sizes of 30 or fewer
      must be interpreted cautiously. Studies can be considered well powered if the
      sample size is 50 even if only a one-grade difference in median VGE grade is of
      interest.

PMID- 24687481
TI  - Decompression illness in divers treated in Auckland, New Zealand, 1996-2012.
AB  - INTRODUCTION: The treatment of divers for decompression illness (DCI) in
      Auckland, New Zealand, has not been described since 1996, and subsequent trends
      in patient numbers and demographics are unmeasured. METHODS: This was a
      retrospective audit of DCI cases requiring recompression in Auckland between 01
      January 1996 and 31 December 2012. Data describing patient demographics, dive
      characteristics, presentation of DCI and outcomes were extracted from case notes
      and facility databases. Trends in annual case numbers were evaluated using
      Spearman's correlation coefficients (rho) and compared with trends in entry-level
      diver certifications. Trends in patient demographics and delay between diving and
      recompression were evaluated using regression analyses. RESULTS: There were 520
      DCI cases. Annual caseload decreased over the study period (rho = 0.813, P <
      0.0001) as did entry level diving certifications in New Zealand (rho = 0.962, P <
      0.0001). Mean diver age was 33.6 (95% confidence limits (CI) 32.7 to 34.5) years
      and age increased (P < 0.0001) over the study period. Median (range) delay to
      recompression was 2.06 (95% CI 0.02 to 23.6) days, and delay declined over the
      study period (P = 0.005). CONCLUSIONS: Numbers of DCI cases recompressed in
      Auckland have declined significantly over the last 17 years. The most plausible
      explanation is declining diving activity but improvements in diving safety cannot
      be excluded. The delay between diving and recompression has reduced.

PMID- 24687482
TI  - Neuron-specific enolase and S100B protein levels in recreational scuba divers
      with neurological decompression sickness.
AB  - INTRODUCTION: Neuron-specific enolase (NSE) and S100B protein are brain-origin
      proteins commonly described to assess the presence and severity of neurological
      injury. To date, there are limited data examining the influence of scuba diving
      on these biomarkers, particularly when symptoms of decompression sickness (DCS)
      occur. The purpose of this controlled study was to determine whether these serum
      neurochemical markers could be used as 1) indicators of neurological DCS and 2)
      predictors of incomplete recovery. METHODS: Fifty-nine divers with neurological
      DCS and 37 asymptomatic divers admitted for inadequate decompression, serving as
      controls, were consecutively enrolled between 2010 and 2012. Blood samples were
      collected at initial presentation up to 6 hours after dive completion (controls)
      or onset of symptoms (DCS divers). Biomarkers were quantified in nonhaemolysed
      samples only. Clinical outcome was assessed at 6 months post-injury. RESULTS: The
      two groups did not differ regarding the variables examined, except for the total
      dive time which was slightly shorter in the control group. NSE, but not S100B
      protein, was higher in the DCS group than in controls (P < 0.0001). An NSE level
      > 15.9 ug L-1 determined by ROC analysis predicted DCS development with a
      specificity of 100% (95% confidence interval (CI) 90 to 100) and a sensitivity of
      24% (95% CI 14 to 36). There was a trend towards a higher likelihood of residual
      neurological deficits above this cut-off value (P = 0.08). CONCLUSIONS: Early
      determination of NSE was found to be useful for the diagnosis of neurological DCS
      with a high specificity. However, its clinical applicability in decision making
      for determining treatment as well as its prognostic value remains to be
      established. Reliability of S100B protein was not demonstrated in the present
      study.

PMID- 24687483
TI  - An in-vitro examination of the effect of vinegar on discharged nematocysts of
      Chironex fleckeri.
AB  - OBJECTIVE: To determine the effect acetic acid (vinegar) has on discharged
      nematocysts in a simulated sting from Chironex fleckeri. METHOD: This research
      was performed in 2 parts: 1 C. fleckeri tentacles placed on amniotic membrane
      were electrically stimulated, and venom washings collected before and after
      application of vinegar. Lyophilised venom washings were run through a fast
      performance protein liquid chromatography column to confirm the venom profile,
      with a quantitative measure of venom from each washing calculated using UNICORNTM
      software. 2 The toxicity of the washings was determined by application to human
      cardiomyocytes, with percentage of cell detachment providing a measure of cell
      mortality, and hence toxicity. RESULTS: Part 1: There was a 69 +/- 32% (F = 77, P
      < 0.001) increase in venom discharge after vinegar was applied compared to post
      electrical stimulation. Part 2: Venom collected after the administration of
      vinegar demonstrated the same toxicity as venom from electrically stimulated C.
      fleckeri tentacles and milked venom, causing cell mortality of 59 +/- 13% at 10
      ug ml-1 compared to 57 +/- 10% and 65 +/- 7% respectively. CONCLUSION: This in
      vitro research suggests that vinegar promotes further discharge of venom from
      already discharged nematocysts. This raises concern that vinegar has the
      potential to do harm when used as first aid in C. fleckeri envenomation.

PMID- 24687484
TI  - Ultrasound detection of vascular decompression bubbles: the influence of new
      technology and considerations on bubble load.
AB  - INTRODUCTION: Diving often causes the formation of 'silent' bubbles upon
      decompression. If the bubble load is high, then the risk of decompression
      sickness (DCS) and the number of bubbles that could cross to the arterial
      circulation via a pulmonary shunt or patent foramen ovale increase. Bubbles can
      be monitored aurally, with Doppler ultrasound, or visually, with two dimensional
      (2D) ultrasound imaging. Doppler grades and imaging grades can be compared with
      good agreement. Early 2D imaging units did not provide such comprehensive
      observations as Doppler, but advances in technology have allowed development of
      improved, portable, relatively inexpensive units. Most now employ harmonic
      technology; it was suggested that this could allow previously undetectable
      bubbles to be observed. METHODS: This paper provides a review of current methods
      of bubble measurement and how new technology may be changing our perceptions of
      the potential relationship of these measurements to decompression illness.
      Secondly, 69 paired ultrasound images were made using conventional 2D ultrasound
      imaging and harmonic imaging. Images were graded on the Eftedal-Brubakk (EB)
      scale and the percentage agreement of the images calculated. The distribution of
      mismatched grades was analysed. RESULTS: Fifty-four of the 69 paired images had
      matching grades. There was no significant difference in the distribution of high
      or low EB grades for the mismatched pairs. CONCLUSIONS: Given the good level of
      agreement between pairs observed, it seems unlikely that harmonic technology is
      responsible for any perceived increase in observed bubble loads, but it is
      probable that our increasing use of 2D ultrasound to assess dive profiles is
      changing our perception of 'normal' venous and arterial bubble loads. Methods to
      accurately investigate the load and size of bubbles developed will be helpful in
      the future in determining DCS risk.

PMID- 24687485
TI  - Cutaneous decompression sickness.
AB  - A probable case of decompression illness with associated cutis marmorata is
      presented, which regressed over a few hours with oxygen breathing and after
      intravenous methylprednisolone and fluid resuscitation without recompression. He
      was eventually transferred for hyperbaric treatment some 10 hours post dive.
      Cutaneous decompression illness is not associated with high mortality per se, but
      prompt and accurate recognition is warranted, as it may represent a prodromal
      feature of potentially life-threatening complications. However, in this case, as
      differential diagnosis, an allergic reaction remains possible. 

PMID- 24687486
TI  - Issues around household pharmaceutical waste disposal through community
      pharmacies in Croatia.
AB  - BACKGROUND: Croatian regulations mandate pharmacies to receive unused medicines
      from households. Pharmacies are considered as producers and holders of
      pharmaceutical waste and are obliged to finance this service. Model where
      pharmacies are responsible for financing disposal of unused medicines without
      reimbursement is not common in Europe. Present service was not tested before
      implementation. OBJECTIVE: To investigate the elements of the pharmaceutical
      waste disposal service provided by pharmacies, and to gain insight into the
      factors that might influence the effectiveness of the service. Setting All
      pharmacies in the city of Zagreb. METHOD: Each pharmacy was asked to weigh the
      collected waste from the public during a period of 30 days, between June 1st and
      July 10th of 2011, absent from any media advertisement and answer a specifically
      designed questionnaire that was exploring possible connections between the amount
      of collected waste, type of pharmacy ownership, discretion while disposing,
      location of the container, appropriate labeling and to compare the amount of
      collected waste between neighborhoods. MAIN OUTCOME MEASURE: Quantity of
      collected unused medicines from the public. RESULTS: Of 210 pharmacies, 91
      participated completing the questionnaire (43 % response rate). The total amount
      of collected waste was 505 kg. Pharmacies owned by the city of Zagreb had higher
      response rate (74 %) than privately owned pharmacies (36 %), and collected
      significantly higher amount of waste. Anonymity when disposing influenced
      collected quantity, while labelling and location of the container did not. There
      were differences in the amount of collected waste between neighborhoods due to
      the demographic characteristics and number of pharmacies per capita. CONCLUSION:
      The effectiveness of the pharmacy service of collecting unused medicines in
      Croatia shows a number of weaknesses. The amount of collected medicines is below
      the European average. Functioning of the service seems to be negatively
      influenced by the type of pharmacy ownership, distribution of pharmacies and lack
      of anonymity when disposing unused medicines. Additionally, type of ownership is
      connected with financial burden for pharmacies. Governmental bodies should
      examine current legislation regulating pharmaceutical waste disposal,
      particularly financial responsibility for providing the service, in order to
      increase pharmacies' compliance. Advertising of the service may increase
      awareness of the importance of proper disposal of unused medicines.

PMID- 24687487
TI  - Simultaneous reduction of MAD2 and BUBR1 expression induces mitotic spindle
      alterations associated with p53 dependent cell cycle arrest and death.
AB  - Most human tumors are characterized by aneuploidy that is believed to be the
      consequence of chromosomal instability (CIN). The mechanism(s) leading to
      aneuploidy and the pathways that allow its tolerance are not completely
      understood. The Spindle Assembly Checkpoint (SAC) is a cellular surveillance
      mechanism working during mitosis, and alterations of genes that encode components
      of the SAC weakening the mitotic checkpoint, induce aneuploidy by chromosome mis
      segregation. We induced aneuploidy in near-diploid tumor cells by simultaneous
      depletion of the SAC proteins MAD2 and BUBR1 by RNA interference in the attempt
      to gain further insight on the cellular responses to aneuploidy. Individual
      reduction of MAD2 and BUBR1 protein levels caused defective mitosis and
      aneuploidy, while co-depletion of MAD2 and BUBR1 caused cell cycle arrest and
      cell death in addition to aneuploidy. The simultaneous reduction of the two SAC
      proteins induced high percentage of hyperdiploid cells and p53 stabilization
      suggesting that hyperdiploidy could activate a p53 controlled pathway. The
      results indicate that p53 is required to induce cell cycle arrest and cell death
      when the mitotic checkpoint is strongly perturbed, thereby preventing aneuploid
      cell propagation. 

PMID- 24687488
TI  - Coupling of fluorescence correlation spectroscopy with capillary and microchannel
      analytical systems and its applications.
AB  - In the past decade, fluorescence correlation spectroscopy (FCS) has become an
      ultrasensitive and noninvasive single-molecule detection technique, which is
      widely applied in the physical, chemical, and life-science research. The coupling
      of FCS with narrow channel flow systems including the ones based on capillary
      provide the important, convenient, and sensitive assay platforms for probing and
      understanding the behavior of single molecules or nanoparticles with improved
      temporal and spatial resolution and need for less sample volume among other
      advantages. This review focus on different approaches for FCS with capillary and
      microchannel analytical systems and its applications in confined diffusion study,
      flow profiles, and imaging of narrow channel, multicomponent analyses such as
      protein, DNA analysis, and characterization on nanoparticles. 

PMID- 24687489
TI  - Discovery of novel cell wall-active compounds using P ywaC, a sensitive reporter
      of cell wall stress, in the model gram-positive bacterium Bacillus subtilis.
AB  - The emergence of antibiotic resistance in recent years has radically reduced the
      clinical efficacy of many antibacterial treatments and now poses a significant
      threat to public health. One of the earliest studied well-validated targets for
      antimicrobial discovery is the bacterial cell wall. The essential nature of this
      pathway, its conservation among bacterial pathogens, and its absence in human
      biology have made cell wall synthesis an attractive pathway for new antibiotic
      drug discovery. Herein, we describe a highly sensitive screening methodology for
      identifying chemical agents that perturb cell wall synthesis, using the model of
      the Gram-positive bacterium Bacillus subtilis. We report on a cell-based pilot
      screen of 26,000 small molecules to look for cell wall-active chemicals in real
      time using an autonomous luminescence gene cluster driven by the promoter of
      ywaC, which encodes a guanosine tetra(penta)phosphate synthetase that is
      expressed under cell wall stress. The promoter-reporter system was generally much
      more sensitive than growth inhibition testing and responded almost exclusively to
      cell wall-active antibiotics. Follow-up testing of the compounds from the pilot
      screen with secondary assays to verify the mechanism of action led to the
      discovery of 9 novel cell wall-active compounds. 

PMID- 24687490
TI  - High proportion of heteroresistance in gyrA and gyrB in fluoroquinolone-resistant
      Mycobacterium tuberculosis clinical isolates.
AB  - Heteroresistance is the coexistence of populations with differing nucleotides at
      a drug resistance locus within a sample of organisms. Although Sanger sequencing
      is the gold standard for sequencing, it may be less sensitive than deep
      sequencing for detecting fluoroquinolone heteroresistance in Mycobacterium
      tuberculosis. Twenty-seven fluoroquinolone monoresistant and 11 fluoroquinolone
      susceptible M. tuberculosis isolates were analyzed by Sanger and Illumina deep
      sequencing. Individual sequencing reads were analyzed to detect heteroresistance
      in the gyrA and gyrB genes. Heteroresistance to fluoroquinolones was identified
      in 10/26 (38%) phenotypically fluoroquinolone-resistant samples and 0/11 (P =
      0.02) fluoroquinolone-susceptible controls. One resistant sample was excluded
      because of contamination with the laboratory strain M. tuberculosis H37Rv. Sanger
      sequencing revealed resistance-conferring mutations in 15 isolates, while deep
      sequencing revealed mutations in 20 isolates. Isolates with fluoroquinolone
      resistance-conferring mutations by Sanger sequencing all had at least those same
      mutations identified by deep sequencing. By deep sequencing, 10 isolates had a
      single fixed (defined as >95% frequency) mutation, while 10 were heteroresistant,
      5 of which had a single unfixed (defined as <95% frequency) mutation and 5 had
      multiple unfixed mutations. Illumina deep sequencing identified a higher
      proportion of fluoroquinolone-resistant M. tuberculosis isolates with
      heteroresistance than did Sanger sequencing. The heteroresistant isolates
      frequently demonstrated multiple mutations, but resistant isolates with fixed
      mutations each had only a single mutation. 

PMID- 24687491
TI  - In vitro and in vivo activities of tigecycline-colistin combination therapies
      against carbapenem-resistant Enterobacteriaceae.
AB  - We assessed the activity of tigecycline (TGC) combined with colistin (COL)
      against carbapenem-resistant enterobacteria. Synergy occurred in vitro against
      the majority of isolates, with the exception of Serratia marcescens. In a simple
      animal model (Galleria mellonella), TGC-COL was superior (P < 0.01) in treating
      Escherichia coli, Klebsiella pneumoniae, and Enterobacter infections, including
      those with TGC-COL resistance. Clinical studies are needed to determine whether
      TGC-COL regimens may be a viable option. 

PMID- 24687492
TI  - Evaluation of imipenem for prophylaxis and therapy of Yersinia pestis delivered
      by aerosol in a mouse model of pneumonic plague.
AB  - It has been previously shown that mice subjected to an aerosol exposure to
      Yersinia pestis and treated with beta-lactam antibiotics after a delay of 42 h
      died at an accelerated rate compared to controls. It was hypothesized that
      endotoxin release in antibiotic-treated mice accounted for the accelerated death
      rate in the mice exposed to aerosol Y. pestis. Imipenem, a beta-lactam
      antibiotic, binds to penicillin binding protein 2 with the highest affinity and
      produces rounded cells. The binding of imipenem causes cells to lyse quickly and
      thereby to release less free endotoxin. Two imipenem regimens producing fractions
      of time that the concentration of free, unbound drug was above the MIC (fT>MIC)
      of approximately 25% (6/24 h) and 40% (9.5/24 h) were evaluated. In the
      postexposure prophylaxis study, the 40% and 25% regimens produced 90% and 40%
      survivorship, respectively. In the 42-h treatment study, both regimens
      demonstrated a 40 to 50% survivorship at therapy cessation and some deaths
      thereafter, resulting in a 30% survivorship. As this was an improvement over the
      results with other beta-lactams, a comparison of both endotoxin and cytokine
      levels in mice treated with imipenem and ceftazidime (a beta-lactam previously
      demonstrated to accelerate death in mice during treatment) was performed and
      supported the original hypotheses; however, the levels observed in animals
      treated with ciprofloxacin (included as an unrelated antibiotic that is also
      bactericidal but should cause little lysis due to a different mode of action)
      were elevated and significantly (7-fold) higher than those with ceftazidime. 

PMID- 24687493
TI  - Assessment of Mycobacterium tuberculosis pantothenate kinase vulnerability
      through target knockdown and mechanistically diverse inhibitors.
AB  - Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the
      first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In
      our earlier reports, we had established that the type I isoform encoded by the
      coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and
      this vital information was then exploited to screen large libraries for
      identification of mechanistically different classes of PanK inhibitors. The
      present report summarizes the synthesis and expansion efforts to understand the
      structure-activity relationships leading to the optimization of enzyme inhibition
      along with antimycobacterial activity. Additionally, we report the progression of
      two distinct classes of inhibitors, the triazoles, which are ATP competitors, and
      the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization
      studies provided evidence of these inhibitors binding to the enzyme. This was
      further substantiated with the biaryl acids having MIC against the wild-type M.
      tuberculosis strain and the subsequent establishment of a target link with an
      upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP
      competitors had cellular activity only in a M. tuberculosis knockdown strain with
      reduced PanK expression levels. Additionally, in vitro and in vivo survival
      kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain
      indicated that the target levels have to be significantly reduced to bring in
      growth inhibition. The dual approaches employed here thus established the poor
      vulnerability of PanK in M. tuberculosis. 

PMID- 24687494
TI  - Characterization of sal(A), a novel gene responsible for lincosamide and
      streptogramin A resistance in Staphylococcus sciuri.
AB  - Natural resistance to lincosamides and streptogramins A (LSA), which is a species
      characteristic of Bacillus subtilis and Enterococcus faecalis, has never been
      documented in the Staphylococcus genus. We investigate here the molecular basis
      of the LSA phenotype exhibited by seven reference strains of Staphylococcus
      sciuri, including the type strains of the three described subspecies. By whole
      genome sequencing of strain ATCC 29059, we identified a candidate gene that
      encodes an ATP-binding cassette protein similar to the Lsa and VmlR resistance
      determinants. Isolation and reverse transcription-quantitative PCR (qRT-PCR)
      expression studies confirmed that Sal(A) can confer a moderate resistance to
      lincosamides (8 times the MIC of lincomycin) and a high-level resistance to
      streptogramins A (64 times the MIC of pristinamycin II). The chromosomal location
      of sal(A) between two housekeeping genes of the staphylococcal core genome
      supports the gene's ancient origins and thus innate resistance to these
      antimicrobials within S. sciuri subspecies. 

PMID- 24687495
TI  - Antifungal susceptibility patterns of opportunistic fungi in the genera
      Verruconis and Ochroconis.
AB  - Species of Verruconis and species of Ochroconis are dematiaceous fungi generally
      found in the environment but having the ability to infect humans, dogs, cats,
      poultry, and fish. This study presents the antifungal susceptibility patterns of
      these fungi at the species level. Forty strains originating from clinical and
      environmental sources were phylogenetically identified at the species level by
      using sequences of the ribosomal DNA internal transcribed spacer (rDNA ITS). In
      vitro antifungal susceptibility testing was performed against eight antifungals,
      using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution
      method. The geometric mean MICs for amphotericin B (AMB), flucytosine (5FC),
      fluconazole (FLC), itraconazole (ITC), voriconazole (VRC), and posaconazole (POS)
      and minimum effective concentrations (MECs) for caspofungin (CAS) and
      anidulafungin (AFG) across the Ochroconis and Verruconis species were as follows,
      in increasing order. For Verruconis species, the values (MUg/ml) were as follows:
      AFG, 0.04; POS, 0.25; ITC, 0.37; AMB, 0.50; CAS, 0.65; VRC, 0.96; 5FC, 10.45; and
      FLC, 47.25. For Ochroconis species, the values (MUg/ml) were as follows: AFG,
      0.06; POS, 0.11; CAS, 0.67; VRC, 2.76; ITC, 3.94; AMB, 5.68; 5FC, 34.48; and FLC,
      61.33. Antifungal susceptibility of Ochroconis and Verruconis was linked with
      phylogenetic distance and thermotolerance. Echinocandins and POS showed the
      greatest in vitro activity, providing possible treatment options for Ochroconis
      and Verruconis infections. 

PMID- 24687496
TI  - Population pharmacokinetic/pharmacodynamic analysis of the bactericidal
      activities of sutezolid (PNU-100480) and its major metabolite against
      intracellular Mycobacterium tuberculosis in ex vivo whole-blood cultures of
      patients with pulmonary tuberculosis.
AB  - Sutezolid (PNU-100480 [U-480]) is an oxazolidinone antimicrobial being developed
      for the treatment of tuberculosis. An active sulfoxide metabolite (PNU-101603 [U
      603]), which reaches concentrations in plasma several times those of the parent,
      has been reported to drive the killing of extracellular Mycobacterium
      tuberculosis by sutezolid in hollow-fiber culture. However, the relative
      contributions of the parent and metabolite against intracellular M. tuberculosis
      in vivo are not fully understood. The relationships between the plasma
      concentrations of U-480 and U-603 and intracellular whole-blood bactericidal
      activity (WBA) in ex vivo cultures were examined using a direct competitive
      population pharmacokinetic (PK)/pharmacodynamic 4-parameter sigmoid model. The
      data set included 690 PK determinations and 345 WBA determinations from 50
      tuberculosis patients enrolled in a phase 2a sutezolid trial. The model
      parameters were solved iteratively. The median U-603/U-480 concentration ratio
      was 7.1 (range, 1 to 28). The apparent 50% inhibitory concentration of U-603 for
      intracellular M. tuberculosis was 17-fold greater than that of U-480 (90%
      confidence interval [CI], 9.9- to 53-fold). Model parameters were used to
      simulate in vivo activity after oral dosing with sutezolid at 600 mg twice a day
      (BID) and 1,200 mg once a day (QD). Divided dosing resulted in greater cumulative
      activity (-0.269 log10 per day; 90% CI, -0.237 to -0.293 log10 per day) than
      single daily dosing (-0.186 log10 per day; 90% CI, -0.160 to -0.208 log10 per
      day). U-480 accounted for 84% and 78% of the activity for BID and QD dosing,
      respectively, despite the higher concentrations of U-603. Killing of
      intracellular M. tuberculosis by orally administered sutezolid is mainly due to
      the activity of the parent compound. Taken together with the findings of other
      studies in the hollow-fiber model, these findings suggest that sutezolid and its
      metabolite act on different mycobacterial subpopulations. 

PMID- 24687497
TI  - Abnormal weight gain and gut microbiota modifications are side effects of long
      term doxycycline and hydroxychloroquine treatment.
AB  - Doxycycline has been proposed for the treatment of malnourished children in
      developing countries, and its use has been associated with weight gain in healthy
      volunteers. No previous studies have assessed abnormal weight gain as a putative
      side effect of long-term doxycycline treatment; thus, the objective of the
      present study was to characterize this phenomenon. We also analyzed the role of
      the gut microbiota in this effect. We assessed changes in the body mass index in
      Q fever endocarditis patients treated with doxycycline and hydroxychloroquine and
      healthy individuals with no antibiotic treatment. Abnormal weight gain was
      defined as a gain in weight above that of the controls. The fecal samples were
      examined using molecular assays for Methanobrevibacter smithii, Bacteroidetes,
      Firmicutes, Escherichia coli, Lactobacillus, Lactobacillus reuteri, and total
      bacterial concentrations. We examined 82 patients, including 48 patients with Q
      fever endocarditis and 34 controls. Approximately 23% of the treated patients
      showed abnormal weight gain (P = 0.001). Patients treated with doxycycline and
      hydroxychloroquine presented significantly lower concentrations of Bacteroidetes
      (P = 0.002), Firmicutes (P = 0.01), and Lactobacillus (P = 0.02). The linear
      regression analysis revealed that the duration of treatment was significantly
      associated with a decrease in Bacteroidetes (P = 0.0001), Firmicutes (P = 0.002),
      and total bacteria (P < 0.00001). Abnormal weight gain is a side effect of long
      term doxycycline and hydroxychloroquine treatment. Gut microbiota modifications
      at the phylum level could play an instrumental role in this effect. We highlight
      the need for specific nutritional care in patients undergoing long-term
      antibiotic treatment, particularly treatment involving the use of doxycycline. 

PMID- 24687498
TI  - The combination of alisporivir plus an NS5A inhibitor provides additive to
      synergistic anti-hepatitis C virus activity without detectable cross-resistance.
AB  - Alisporivir (ALV), a cyclophilin inhibitor, is a host-targeting antiviral (HTA)
      with multigenotypic anti-hepatitis C virus (HCV) activity and a high barrier to
      resistance. Recent advances have supported the concept of interferon (IFN)-free
      regimens to treat chronic hepatitis C. As the most advanced oral HTA, ALV with
      direct-acting antivirals (DAAs) represents an attractive drug combination for IFN
      free therapy. In this study, we investigated whether particular DAAs exhibit
      additive, synergistic, or antagonistic effects when combined with ALV. Drug
      combinations of ALV with NS3 protease, NS5B polymerase, and NS5A inhibitors were
      investigated in HCV replicons from genotypes 1a, 1b, 2a, 3, and 4a (GT1a to -4a).
      Combinations of ALV with DAAs exerted an additive effect on GT1 and -4. A
      significant and specific synergistic effect was observed with ALV-NS5A inhibitor
      combination on GT2 and -3. Furthermore, ALV was fully active against DAA
      resistant variants, and ALV-resistant variants were fully susceptible to DAAs.
      ALV blocks the contact between cyclophilin A and domain II of NS5A, and NS5A
      inhibitors target domain I of NS5A; our data suggest a molecular basis for the
      use of these two classes of inhibitors acting on two distinct domains of NS5A.
      These results provide in vitro evidence that ALV with NS5A inhibitor combination
      represents an attractive strategy and a potentially effective IFN-free regimen
      for treatment of patients with chronic hepatitis C. Due to its high barrier and
      lack of cross-resistance, ALV could be a cornerstone drug partner for DAAs. 

PMID- 24687499
TI  - Factors associated with ceftriaxone nonsusceptibility of Streptococcus
      pneumoniae: analysis of South African national surveillance data, 2003 to 2010.
AB  - It is important to monitor beta-lactam antimicrobial nonsusceptibility trends for
      Streptococcus pneumoniae to inform empirical treatment guidelines. In this study,
      we describe penicillin and ceftriaxone susceptibility trends using national
      laboratory-based pneumococcal surveillance data from 2003 to 2010. A sentinel
      enhanced-site patient subset (2009 to 2010) contributed to the risk factor and
      mortality analyses. We included 9,218 invasive pneumococcal disease (IPD) cases
      for trend analyses and 2,854 IPD cases for risk factor and mortality analyses.
      Overall, we detected no significant changes in penicillin (patients <5 years of
      age, P = 0.50; patients >= 5 years of age, P = 0.05) or ceftriaxone
      nonsusceptibility rates (patients <5 years of age, P = 0.21; patients >= 5 years
      of age, P = 0.60). Factors associated with ceftriaxone nonsusceptibility on
      multivariate analysis were an age of <5 years (<1 year of age: adjusted odds
      ratio [aOR], 2.87; 95% confidence interval [CI], 1.70 to 4.86; 1 to 4 years of
      age: aOR, 2.58; 95% CI, 1.53 to 4.35, versus 25 to 44 years of age), province
      (Gauteng [aOR, 2.46; 95% CI, 1.26 to 4.84], and Northern Cape [aOR, 4.52; 95% CI,
      1.95 to 10.52] versus KwaZulu-Natal), beta-lactam use within 24 h preceding
      admission (aOR, 2.52; 95% CI, 1.41 to 4.53), and 13-valent vaccine serotypes
      (aOR, 51.64; 95% CI, 7.18 to 371.71). Among patients >= 5 years of age with
      meningitis who were treated according to current guidelines, HIV-infected
      patients (aOR, 2.94; 95% CI, 1.32 to 6.54) and patients infected with ceftriaxone
      nonsusceptible isolates (aOR, 3.17; 95% CI, 1.27 to 7.89) had increased mortality
      rates. Among children <5 years of age with meningitis, mortality was increased in
      HIV-infected patients (aOR, 3.04; 95% CI, 1.40 to 6.56) but not in those with
      ceftriaxone-nonsusceptible isolates. Penicillin and ceftriaxone nonsusceptibility
      remained stable over the study period. Ceftriaxone nonsusceptibility was
      associated with increased mortality among patients >=5 years of age with
      meningitis. The introduction of a pneumococcal conjugate vaccine may reduce
      ceftriaxone-nonsusceptible meningitis.

PMID- 24687500
TI  - Deoxysugars as antituberculars and alpha-mannosidase inhibitors.
AB  - A promising modified sugar molecule was identified which was active against
      multidrug-resistant (MDR) strains of Mycobacterium tuberculosis, suggesting
      involvement of a new target. The compound was demonstrated to be bactericidal,
      inhibited the growth of M. tuberculosis in mice, and targeted alpha-mannosidase
      as a competitive inhibitor with a Ki value of 353.9 MUM. 

PMID- 24687501
TI  - Biochemical analysis of metallo-beta-lactamase NDM-3 from a multidrug-resistant
      Escherichia coli strain isolated in Japan.
AB  - New Delhi metallo-beta-lactamase-3 (NDM-3) was identified in a multidrug
      resistant Escherichia coli isolate, NCGM77, obtained from the feces of a patient
      in Japan. The enzymatic activities of NDM-3 against beta-lactams were similar to
      those of NDM-1, although NDM-3 showed slightly lower kcat/Km ratios for all the
      beta-lactams tested except for doripenem. The genetic context for blaNDM-3 was
      tnpA-blaNDM-3-bleMBL-trpF-dsbC-tnpA-sulI-qacEdeltaI-aadA2-dfrA1, which was
      present on an approximately 250-kb plasmid. 

PMID- 24687502
TI  - Bumped kinase inhibitor 1294 treats established Toxoplasma gondii infection.
AB  - Toxoplasma gondii is a unicellular parasite that causes severe brain and eye
      disease. Current drugs for T. gondii are limited by toxicity. Bumped kinase
      inhibitors (BKIs) selectively inhibit calcium-dependent protein kinases of the
      apicomplexan pathogens T. gondii, cryptosporidia, and plasmodia. A lead anti
      Toxoplasma BKI, 1294, has been developed to be metabolically stable and orally
      bioavailable. Herein, we demonstrate the oral efficacy of 1294 against
      toxoplasmosis in vivo. 

PMID- 24687503
TI  - Correlation between plasma, intracellular, and cervical tissue levels of
      raltegravir at steady-state dosing in healthy women.
AB  - Raltegravir is an antiretroviral with potential value for preexposure prophylaxis
      (PrEP) against HIV, but the intracellular pharmacokinetics in genital tissue have
      not been described. In this study, healthy, HIV-uninfected nonpregnant women took
      400 mg of raltegravir twice daily for 22 days. On day 8, 15, and 22, blood was
      collected 0, 4, 6, 8, and 12 h and cervical biopsy specimens taken 0, 6, and 12 h
      after raltegravir dosing. Plasma and intracellular raltegravir concentrations in
      peripheral blood mononuclear cells (PBMC) and cervical tissue were measured by
      tandem mass spectrometry. Linear mixed effects models evaluated correlations
      between different sample types, as well as differences in concentration between
      phases of the menstrual cycle. Ten women were enrolled: 9 completed all three
      visits and 1 completed two visits. The age (mean +/- standard deviation) of
      participants was 30 +/- 8 years. Trough plasma concentrations of raltegravir 12 h
      after a directly observed dose were above the HIV 95% inhibitory concentration
      (IC95) of 33 nM (14.6 ng/ml) in 96% of measurements, compared to 67% of PBMC and
      89% of cervical tissue trough values. Across all measurements, only 2% (3/135) of
      plasma values fell below the IC95, compared to 10% (13/135) for PBMC and 6%
      (5/81) for cervical tissue. There was no impact of menstrual phase on raltegravir
      concentrations. In conclusion, cervical tissue raltegravir concentrations were no
      greater than plasma concentrations, and ~10% of all cervical tissue trough values
      were below the IC95, making the current twice-daily formulation of raltegravir
      impractical for PrEP. 

PMID- 24687504
TI  - Efficacy and pharmacological mechanism of pronase-enhanced low-dose antibiotics
      for Helicobacter pylori eradication.
AB  - This study examined the efficacy and pharmacological mechanism of pronase
      assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian
      gerbils infected with H. pylori received 7-day treatment (omeprazole, different
      concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was
      assessed using the eradication rate and the colonization of H. pylori. In
      Mongolian gerbils orally administered pronase, the thickness of the gastric
      mucous layer (GML) was examined using immunohistochemical and alcian blue
      staining, and the concentrations of amoxicillin in gastric tissue and serum were
      detected using high-performance liquid chromatography (HPLC). The eradication
      rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7%
      (13/15) in the high-antibiotic group (HAG) (P = 1.000). The antibiotic dose in
      the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with
      pronase, the sticky protein of the GML was hydrolyzed, and the GML became
      thinner. Higher amoxicillin concentrations in both the gastric tissue and serum
      were observed in the pronase group than in the Am10 group. The concentration of
      amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher
      than in the Am10 group in 5 min. Together, these data suggest that pronase
      significantly reduced the dose of antibiotics used in H. pylori eradication. The
      pharmacological mechanism is likely pronase removal of the mucus layer, promoting
      chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing
      the antibiotic concentrations in the deep GML, which acted on H. pylori
      collectively. Thus, pronase may enhance the level of antibiotics for eradication
      of H. pylori in the clinic. 

PMID- 24687505
TI  - In vitro and in vivo efficacy of novel flavonoid dimers against cutaneous
      leishmaniasis.
AB  - Treatment of leishmaniasis by chemotherapy remains a challenge because of limited
      efficacy, toxic side effects, and drug resistance. We previously reported that
      synthetic flavonoid dimers have potent antipromastigote and antiamastigote
      activity against Leishmania donovani, the causative agent of visceral
      leishmaniasis. Here, we further investigate their leishmanicidal activities
      against cutaneous Leishmania species. One of the flavonoid dimers (compound 39)
      has marked antipromastigote (50% inhibitory concentrations [IC50s], 0.19 to 0.69
      MUM) and antiamastigote (IC50s, 0.17 to 2.2 MUM) activities toward different
      species of Leishmania that cause cutaneous leishmaniasis, including Leishmania
      amazonensis, Leishmania braziliensis, Leishmania tropica, and Leishmania major.
      Compound 39 is not toxic to peritoneal elicited macrophages, with IC50 values
      higher than 88 MUM. In the mouse model of cutaneous leishmaniasis induced by
      subcutaneous inoculation of L. amazonensis in mouse footpads, intralesional
      administration of 2.5 mg/kg of body weight of compound 39.HCl can reduce footpad
      thickness by 36%, compared with that of controls values. The amastigote load in
      the lesions was reduced 20-fold. The present study suggests that flavonoid dimer
      39 represents a new class of safe and effective leishmanicidal agent against
      visceral and cutaneous leishmaniasis. 

PMID- 24687506
TI  - Evaluation of the pharmacokinetics and pharmacodynamics of liposomal amikacin for
      inhalation in cystic fibrosis patients with chronic pseudomonal infections using
      data from two phase 2 clinical studies.
AB  - The pharmacokinetic-pharmacodynamic (PK-PD) relationships between serum exposure
      measures of liposomal amikacin for inhalation (LAI) and the change in pulmonary
      function test (PFT) measures and number of CFU from baseline were evaluated in
      cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. A
      dose of 70, 140, 280, or 560 mg of LAI or placebo was administered to CF patients
      once daily for 28 days. PFTs and sputum samples for microbiology were assessed on
      days 7, 14, 21, 28, 35 (for log10 CFU), and 56 (for PFTs). Serum, urine, and
      sputum samples were collected for PK evaluation. The relationships between
      efficacy endpoints (relative change in forced expiratory volume in 1 s [FEV1
      {expressed in liters}] and FEV1% predicted and the absolute change in log10 CFU
      of P. aeruginosa from baseline) and exposure measures (dose, day 1 area under the
      curve [AUC], dose/MIC ratio, and day 1 AUC/MIC ratio) and baseline MIC value were
      assessed. The serum and urine PK data were best fit by a 3-compartment model
      (lung, serum, and urine) with linear clearance and interoccasional variation on
      total and renal clearance. Significant univariable relationships between dose or
      day 1 AUC and the relative change in PFT measures (P<=0.017) or the absolute
      change in log10 CFU from baseline (P<=0.037) on the study days were identified.
      Repeated-measures mixed-effects models, which showed dose- and AUC-related
      improvements for each efficacy endpoint (P<=0.041), predicted the observed data
      well. The increases in the relative change in FEV1 and FEV1% predicted of 11% and
      9.9%, respectively, and a 1.23-log10 CFU reduction per 560 mg of LAI estimated on
      day 7 were comparable to the observed increases of 10.7% and 10.3%, respectively,
      and a 1.24-log10 CFU reduction on the same day. The model-estimated PFT effects
      were predicted to be sustained to day 28. An additional 0.451-log10 CFU reduction
      (P=0.022) was estimated on day 14 relative to day 7, with a persistence of effect
      predicted to day 35.

PMID- 24687507
TI  - Activities of ceftazidime and avibactam against beta-lactamase-producing
      Enterobacteriaceae in a hollow-fiber pharmacodynamic model.
AB  - Avibactam is a novel non-beta-lactam beta-lactamase inhibitor that is currently
      undergoing phase 3 clinical trials in combination with ceftazidime. Ceftazidime
      is hydrolyzed by a broad range of beta-lactamases, but avibactam is able to
      inhibit the majority of these enzymes. The studies described here attempt to
      provide insight into the amount of avibactam required to suppress bacterial
      growth in an environment where the concentrations of both agents are varying as
      they would when administered to humans. Following the simulation of a single
      intravenous dose of the drug, ceftazidime alone had no effect on any test
      organism, but a ceftazidime-avibactam combination resulted in rapid killing of
      all of the strains, with growth suppressed for the 8 h of the study. For seven of
      eight strains, this was achieved with a 1-g-250-mg profile, but a 2-g-500-mg
      profile was necessary to completely suppress a high-level-AmpC-producing isolate.
      When ceftazidime was infused continuously for 24 h with a single bolus dose of
      avibactam, rapid killing of all of the strains was again observed, with growth
      suppressed for 10 to >24 h. Regrowth appeared to commence once the avibactam
      concentration dropped below a critical concentration of approximately 0.3 MUg/ml.
      In a third series of studies, ceftazidime was administered every 8 h for 24 h
      with avibactam administered at fixed concentrations for short periods during each
      ceftazidime dose profile. Simulating a 1-g dose of ceftazidime, an avibactam
      pulse of >0.25 and <0.5 MUg/ml was required to suppress growth for 24 h. 

PMID- 24687508
TI  - Altered pharmacokinetics of piperacillin in febrile neutropenic patients with
      hematological malignancy.
AB  - This study assessed the pharmacokinetics and dosing adequacy of piperacillin in
      febrile neutropenic patients after the first dose. Pharmacokinetic analysis was
      performed using noncompartmental methods. We observed an elevated volume of
      distribution (29.7 +/- 8.0 liters [mean +/- standard deviation]) and clearance
      (20.2 +/- 7.5 liters/h) compared to data from other patient populations.
      Antibiotic exposure did not consistently result in therapeutic targets. We
      conclude that alternative dosing strategies guided by therapeutic drug monitoring
      may be required to optimize exposure. 

PMID- 24687509
TI  - Pharmacokinetic interactions between primaquine and chloroquine.
AB  - Chloroquine combined with primaquine has been the standard radical curative
      regimen for Plasmodium vivax and Plasmodium ovale malaria for over half a
      century. In an open-label crossover pharmacokinetic study, 16 healthy volunteers
      (4 males and 12 females) aged 20 to 47 years were randomized into two groups of
      three sequential hospital admissions to receive a single oral dose of 30 mg
      (base) primaquine, 600 mg (base) chloroquine, and the two drugs together. The
      coadministration of the two drugs did not affect chloroquine or
      desethylchloroquine pharmacokinetics but increased plasma primaquine
      concentrations significantly (P <= 0.005); the geometric mean (90% confidence
      interval [CI]) increases were 63% (47 to 81%) in maximum concentration and 24%
      (13 to 35%) in total exposure. There were also corresponding increases in plasma
      carboxyprimaquine concentrations (P <= 0.020). There were no significant
      electrocardiographic changes following primaquine administration, but there was
      slight corrected QT (QTc) (Fridericia) interval lengthening following chloroquine
      administration (median [range] = 6.32 [-1.45 to 12.3] ms; P < 0.001), which was
      not affected by the addition of primaquine (5.58 [1.74 to 11.4] ms; P = 0.642).
      This pharmacokinetic interaction may explain previous observations of synergy in
      preventing P. vivax relapse. This trial was registered at ClinicalTrials.gov
      under reference number NCT01218932. 

PMID- 24687510
TI  - Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic
      response.
AB  - Invasive pulmonary aspergillosis (IPA) is a life-threatening disease of
      immunocompromised patients that requires aggressive therapy. Detection of the
      disease and monitoring of the therapeutic response during IPA are complex, and
      current molecular diagnostics are not suitably robust. Here, we explored
      proteomic profiles of bronchoalveolar lavage fluid (BALF) specimens from a
      persistently neutropenic rabbit model of IPA. Three experimental arms, uninfected
      control animals, infected untreated animals, and animals infected and treated
      with ravuconazole/amphotericin B, were studied. Total proteins were evaluated by
      two-dimensional (2D) gel electrophoresis, followed by matrix-assisted laser
      desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) mass
      spectrometry (MS) and quantified by enzyme-linked immunosorbent assay (ELISA).
      Host-derived proteins haptoglobin (Hp), C-reactive protein (CRP), and annexin A1
      (Anx A1) were prominently found in BALF during the IPA infection and showed
      significant changes in response to antifungal therapy (P < 0.0001). In serum,
      differences in Hp (P = 0.0001) between infected and treated rabbits were
      observed. Preliminary in vitro studies revealed that Aspergillus fumigatus
      secreted proteases may contribute to the cleavage of Anx A1 during IPA. In
      summary, host protein biomarkers Hp, CRP, and Anx A1 may have value in monitoring
      therapeutic response to antifungal agents in IPA patients with confirmed disease.

PMID- 24687511
TI  - Echinocandin failure case due to a previously unreported FKS1 mutation in Candida
      krusei.
AB  - Echinocandins are the preferred therapy for invasive infections due to Candida
      krusei. We present here a case of clinical failure involving C. krusei with a
      characteristic FKS1 hot spot mutation not previously reported in C. krusei that
      was isolated after 14 days of treatment. Anidulafungin MICs were elevated by >= 5
      dilution steps above the clinical breakpoint but by only 1 step for a Candida
      albicans isolate harboring the corresponding mutation, suggesting a notable
      species-specific difference in the MIC increase conferred by this mutation.

PMID- 24687512
TI  - In vitro and in vivo activities of HPi1, a selective antimicrobial against
      Helicobacter pylori.
AB  - A high-throughput screen (HTS) was performed to identify molecules specifically
      active against Helicobacter pylori, the causative agent of peptic ulcer and
      gastric carcinoma. Currently, treatment of H. pylori infection is suboptimal,
      with failure rates approaching 25%, despite triple therapy with two broad
      spectrum antibiotics and a proton pump inhibitor or quadruple therapy with added
      bismuth. The HTS was performed in 384-well plates, and reduction of the metabolic
      indicator resazurin was used as a reporter for cell growth. Diverse molecules
      from commercial sources were identified as hits, and in vitro validations
      included measurements of MIC and time-dependent killing as well as anaerobic
      susceptibility testing against a panel of gut microbes. In vivo validation
      included testing in the mouse model of H. pylori infection. The small molecule
      HPi1 (3-hydrazinoquinoxaline-2-thiol) had excellent potency, with an MIC of 0.08
      to 0.16 MUg/ml and good selectivity for H. pylori compared to a panel of
      commensal bacteria. HPi1 was also effective in a mouse model of H. pylori
      infection, reducing colony counts to below the limit of detection after oral
      dosing of 25 mg/kg/day for 3 days. HPi1 is a promising lead in the search for
      more effective and specific H. pylori therapeutics. 

PMID- 24687513
TI  - Mothers with depression, anxiety or eating disorders: outcomes on their children
      and the role of paternal psychological profiles.
AB  - The present paper aims to longitudinally assess the emotional functioning of
      children of mothers with depression, anxiety, or eating disorders and of mothers
      with no psychological disorders and to evaluate the possible mediating role of
      fathers' psychological profiles on children's internalizing/externalizing
      functioning using SCID I, SCL-90/R and CBCL/11/2-5. The results showed maternal
      psychopathology to be strongly related to children's maladaptive profiles.
      Children of mothers with depression and anxiety showed higher internalizing
      scores than children of other groups. These scores increased from T1 to T2.
      Children of mothers with eating disorders showed higher and increasing
      externalizing scores than children of other groups. The data showed that fathers'
      interpersonal sensitivity, depression, anxiety and psychoticism significantly
      predicted internalizing problems of the children. Moreover, interpersonal
      sensitivity and psychoticism significantly predicted externalizing problems. Our
      results confirmed the impact of maternal psychopathology on maladaptive outcomes
      in their children, which suggests the importance of considering paternal
      psychological profiles. 

PMID- 24687515
TI  - Synthesis of monodispere Au@Co3O4 core-shell nanocrystals and their enhanced
      catalytic activity for oxygen evolution reaction.

PMID- 24687514
TI  - Comparison of a simple-probe real-time PCR and multiplex PCR techniques for HPA-1
      to HPA-6 and HPA-15 genotyping.
AB  - BACKGROUND: We aimed to compare HPA-1 to HPA-6 and HPA-15 genotyping results
      obtained by a simple-probe real-time polymerase chain reaction (PCR) technique
      with the multiplex PCR technique. METHODS: Five hundred DNA samples from the Thai
      National Stem Cell Donor Registry (TSCDR) of the National Blood Centre, Thai Red
      Cross Society were included. Human platelet antigen (HPA) genotyping was
      performed by simple-probe real-time PCR and multiplex PCR techniques. RESULTS:
      HPA-1, HPA-2, HPA-3, and HPA-4 genotyping results obtained by both techniques
      were in agreement. The misinterpretation of HPA-5, HPA-6, and HPA-15 genotypes
      was found in eight samples by simple-probe real-time PCR and HPA genotypes were
      confirmed by DNA sequencing. Two samples of HPA-5 were misinterpreted as HPA-5a5a
      instead of HPA-5a5b due to an NM_002203.3:c.1594A>C mutation (rs199808499) near
      the HPA-5 polymorphism (5' side). Five samples of HPA-6a6b were misinterpreted as
      HPA-6b6b because of an NM_000212.2:c.1545G>A mutation (rs4634) adjacent to the
      HPA-6 polymorphism (3' side). Interestingly, one sample of HPA-15a15b was
      misinterpreted as HPA-15b15b due to an NM_133493.1:c.2118C>A mutation near the
      HPA-15 polymorphism (3' side). CONCLUSIONS: HPA genotyping results by two PCR
      techniques were compared. Incorrect assignments were found due to genetic
      variations near each HPA single nucleotide polymorphism. Therefore, to avoid
      false assignation, the use of two genotyping techniques is recommended.

PMID- 24687516
TI  - Steady-state and synchronous spectrofluorimetric methods for simultaneous
      determination of aliskiren hemifumarate and amlodipine besylate in dosage forms.
AB  - Aliskiren hemifumarate (ALS) and amlodipine besylate (AML) were simultaneously
      determined by two different spectrofluorimetric techniques. The first technique
      depends on direct measurement of the steady-state fluorescence intensities of ALS
      and AML at 313 nm and 452 nm upon excitation at 290 and 375 nm, respectively, in
      a solvent composed of methanol and water (10: 90, v/v). The second technique
      utilizes synchronous fluorimetric quantitative screening of the emission spectra
      of ALS and AML at 272 and 366 nm, respectively using Deltalambda of 97 nm.
      Effects of different solvents and surfactants on relative fluorescence intensity
      were studied. The method was validated according to ICH guidelines. Linearity,
      accuracy and precision were found to be satisfactory in both techniques over the
      concentration ranges of 1-15 and 0.4-4 ug/mL for ALS and AML, respectively. In
      the first technique, limit of detection and limit of quantification were
      estimated and found to be 0.256 and 0.776 ug/mL for ALS as well as 0.067 and
      0.204 ug/mL for AML, respectively. Also, limit of detection and limit of
      quantification were calculated in the synchronous method and found to be 0.293
      and 0.887 ug/mL for ALS as well as 0.034 and 0.103 ug/mL for AML, respectively.
      The methods were successfully applied for the determination of the two drugs in
      their co-formulated tablets. The results were compared statistically with
      reference methods and no significant difference was found. The developed methods
      are rapid, sensitive, inexpensive and accurate for the quality control and
      routine analysis of the cited drugs in bulk and in pharmaceutical preparations
      without pre-separation.

PMID- 24687517
TI  - Impaired limb reaction to displacement of center of gravity in rats with
      unilateral striatal ischemic injury.
AB  - Clinical stroke often results in impaired balance and increased vulnerability to
      severe injuries due to falling. To evaluate potential preclinical treatments that
      might target these deficits, it will be important to include tests capable of
      assessing these impairments chronically in animal models. Previously, we
      developed a postural instability test (PIT) that revealed chronic, unilateral
      impairments in postural stability in rat models of hemi-Parkinson's disease (PD)
      and of unilateral cervical spinal cord injury. Here, we investigated whether this
      test was also capable of revealing long-term stroke-induced impairments in
      postural support in rats. Additionally, we examined the ability of more common
      tests of sensorimotor function to detect chronic impairments. We found that the
      PIT detected chronic deficits in postural stability/balance enduring for up to 6
      weeks post-stroke, outlasting impairments detected in other tests of forelimb
      sensorimotor function, including asymmetries in upright postural support
      (cylinder test) and vibrissae-evoked forelimb placing.

PMID- 24687518
TI  - Only 12 of 211 commissioning groups are acting on integrated care, conference
      hears.

PMID- 24687519
TI  - [Modular reconstruction in acetabular revision with antiprotrusio cages and metal
      augments : the cage-and-augment system].
AB  - OBJECTIVE: Restore primary center of rotation and reconstruct extensive bone
      defects in hip revision surgery with a modular off-label implant combined with
      antiprotrusion cage and metal augment, thus, achieving improved hip function.
      INDICATIONS: Large segmental acetabular defects with nonsupportive columns
      (Paprosky type 3a and 3b) in cup loosening or Girdlestone situation. In case of
      pelvic discontinuity posterior column-plating is possible. CONTRAINDICATIONS:
      Persisting hip infection and severe systemic disorders impairing achievement of
      secondary stability through bony integration of metal augment. SURGICAL
      TECHNIQUE: Posterolateral (if dorsal column plating) or other approach. Remove
      loose implant and granulation tissue with sufficient exposure of bleeding bone.
      Size acetabular defect with trial components of augment and appropriate
      antiprotrusio cage. Fixation of selected metal augment with screws. Fill
      additional acetabular defects with morsellized bone graft. Open a slot into the
      ischium to fix the distal flange of the cage. If necessary, bend both flanges
      according to patient's anatomy. Enter the ischium with distal flange and gradual
      impaction of the antiprotrusio ring. Final stabilization of the ring with several
      screws aiming at the posterior column or the acetabular dome. Inject cement
      between ring and augment to stabilize the construction and avoid metal wear.
      Final cement fixation of a polyethylene liner or a dual-mobility cup into the
      antiprotrusio ring. In pelvic discontinuity with major instability osteosynthesis
      of the dorsal column can be performed prior to cementation. POSTOPERATIVE
      MANAGEMENT: Prophylaxis of periprosthetic infection, DVT and heterotopic
      ossification. Physical therapy with partial weight bearing (20 kp) for 6 weeks;
      in discontinuity initial wheel chair mobilization. RESULTS: Since 2008, 72 off
      label implantations of a combined antiprotrusio cage and a Trabecular MetalTM
      Augment were performed. A total of 44 patients (46 operations) were investigated
      at 38.8 (36-51) months postoperatively. In all, 36 patients had a bone defect
      according to Paprosky type 3a/b and in 3/4 patients with pelvic discontinuity
      additional osteosynthesis was performed. The WOMAC score increased from 39.8 (8.7
      75) points preoperatively to 57.9 (16.7-97.9) points at follow-up. Migration or
      failure of implant components was not observed. In 11 % of dislocations and 11 %
      periprosthetic infections surgical revision was necessary.

PMID- 24687520
TI  - [Periprosthetic bone defects of the hip joint].

PMID- 24687521
TI  - Challenges for the development of bone-forming agents in Europe.

PMID- 24687522
TI  - Major nutrient patterns and bone mineral density among postmenopausal Iranian
      women.
AB  - Our understanding of the influence of overall nutrient intake on bone mineral
      density (BMD) is limited because most studies to date have focused on the intakes
      of calcium, vitamin D, or a few isolated nutrients. Therefore, we examined the
      association of major nutrient patterns with BMD in a sample of postmenopausal
      Iranian women. In this cross-sectional study, 160 women aged 50-85 years were
      studied and their lumbar spine and femoral neck BMDs were measured using dual
      energy X-ray absorptiometry. Dietary intakes were assessed using a validated 168
      item food frequency questionnaire, and daily intakes of 30 nutrients were
      calculated. All nutrient intakes were energy adjusted by the residual method and
      were submitted to principal component factor analysis to identify major nutrient
      patterns. Overall, three major nutrient patterns were identified, among which
      only the first pattern, which was high in folate, total fiber, vitamin B6,
      potassium, vitamin A (as retinol activity equivalent), vitamin C, beta-carotene,
      vitamin K, magnesium, copper, and manganese, had a significant association with
      BMD. After controlling for potential confounders, multivariate adjusted mean of
      the lumbar spine BMD of women in the highest tertile of the first pattern scores
      was significantly higher than those in the lowest tertile (mean difference 0.08;
      95% confidence interval 0.02-0.15; P = 0.01). A nutrient pattern similar to
      pattern 1, which is associated with high intakes of fruits and vegetables, may be
      beneficial for bone health in postmenopausal Iranian women.

PMID- 24687523
TI  - Incidence rates and trends of hip/femur fractures in five European countries:
      comparison using e-healthcare records databases.
AB  - Hip fractures represent a major public health challenge worldwide. Multinational
      studies using a common methodology are scarce. We aimed to estimate the incidence
      rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five
      European countries. The study was performed using seven electronic health-care
      records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the
      United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures
      were calculated for the general population and for those aged >=50 years. Trends
      over time were evaluated using linear regression analysis for both crude and
      standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and
      Spanish DBs varied from 9 to 11 per 10,000 person-years for the general
      population and from 22 to 26 for those >=50 years old; the German DB showed
      slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB
      yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially
      with age in both sexes. The ratio of females to males was >=2 for patients aged
      >=70-79 years in most DBs. Statistically significant trends over time were only
      shown for the UK DB (CPRD) (+0.7% per year, P < 0.01) and the Danish DB (-1.4%
      per year, P < 0.01). IRs of hip/femur fractures varied greatly across European
      countries. With the exception of Denmark, no decreasing trend was observed over
      the study period.

PMID- 24687524
TI  - Physiological effects of microgravity on bone cells.
AB  - Life on Earth developed under the influence of normal gravity (1g). With evidence
      from previous studies, scientists have suggested that normal physiological
      processes, such as the functional integrity of muscles and bone mass, can be
      affected by microgravity during spaceflight. During the life span, bone not only
      develops as a structure designed specifically for mechanical tasks but also
      adapts for efficiency. The lack of weight-bearing forces makes microgravity an
      ideal physical stimulus to evaluate bone cell responses. One of the most serious
      problems induced by long-term weightlessness is bone mineral loss. Results from
      in vitro studies that entailed the use of bone cells in spaceflights showed
      modification in cell attachment structures and cytoskeletal reorganization, which
      may be involved in bone loss. Humans exposed to microgravity conditions
      experience various physiological changes, including loss of bone mass, muscle
      deterioration, and immunodeficiency. In vitro models can be used to extract
      valuable information about changes in mechanical stress to ultimately identify
      the different pathways of mechanotransduction in bone cells. Despite many in vivo
      and in vitro studies under both real microgravity and simulated conditions, the
      mechanism of bone loss is still not well defined. The objective of this review is
      to summarize the recent research on bone cells under microgravity conditions
      based on advances in the field. 

PMID- 24687525
TI  - Heritability of bone mineral density in a multivariate family-based study.
AB  - There is evidence for a genetic contribution to bone mineral density (BMD*).
      Different loci affecting BMD have been identified by diverse linkage and genome
      wide association studies. We studied the heritability of and the correlations
      among six densitometric phenotypes and four bone mass/fracture phenotypes. For
      this purpose, we used a family-based study of the genetics of osteoporosis, the
      Genetic Analysis of Osteoporosis Project. The primary aim of our study was to
      examine the roles of genetic and environmental factors in determining
      osteoporosis-related phenotypes. The project consisted of 11 extended families
      from Spain. All of them were selected through a proband with osteoporosis. BMD
      was measured using dual-energy X-ray absorptiometry. The proportion of variance
      of BMD attributable to significant covariates ranged from 25% (for femoral neck
      BMD) to 48% (for whole-body total BMD). The vast majority of the densitometric
      phenotypes had highly significant heritability, ranging from 0.252 (whole-body
      total BMD) to 0.537 (trochanteric BMD) after correcting for covariate effects.
      All of the densitometric phenotypes showed high and significant genetic
      correlations (from -0.772 to -1.000) with a low bone mass/osteopenia condition
      (Affected 3). Our findings provide additional evidence on the heritability of BMD
      and a strong genetic correlation between BMD and bone mass/fracture phenotypes in
      a Spanish population. Our results emphasize the importance of detecting genetic
      risk factors and the benefit of early diagnosis and especially therapeutic and
      preventive strategies.

PMID- 24687526
TI  - Higher circulating parathormone is associated with smaller and weaker bones in
      obese children.
AB  - Obese children have disadvantageous bone geometry, bone of low quality, and
      reduced strength at non-weight-bearing skeletal sites. The aim of our study was
      to investigate the role of parathormone (PTH) and the Wnt/beta-catenin signaling
      pathway and its inhibitors, sclerostin and Dickkopf-1 (DKK1), as negative
      modulators of fat mass on bone. This was a cross-sectional observational study
      performed in 44 (26 males and 18 females) obese subjects, aged 11.41 +/- 2.61
      years. Thirty-seven normal-weight, healthy children (22 males and 15 females) of
      the same chronological age served as controls for the biochemical parameters and
      bone markers, while the data on bone geometry were evaluated according to our
      normative data obtained previously in a group of 325 control children.
      Digitalized X-rays were evaluated at the level of the second metacarpal bone for
      the determination of bone geometry: total cross-sectional area (TCSA), cortical
      area (CA), medullary area (MA), and bone strength (bending breaking resistance
      index [BBRI]). Serum bone markers (intact procollagen-1N-terminal propeptide
      [P1NP] and serum carboxy-terminal telopeptide of collagen-1 [CTX]), sclerostin,
      DKK1, PTH, 25-hydroxyvitamin D and were also measured. Data for TCSA, CA, MA, and
      BBRI are expressed as a standard deviation score in order to normalize them for
      age and sex. TCSA (mean +/- SD, -2.92 +/- 2.71), CA (-0.60 +/- 0.82), MA (-0.45
      +/- 1.14), and BBRI (-2.65 +/- 2.31) were all significantly smaller than in
      controls (p < 0.01). Serum PTH (36.27 +/- 23.89 vs. 19.33 +/- 11.37 pg/mL) and
      CTX (1.55 +/- 0.44 vs. 1.34 +/- 0.46 ng/mL) were significantly increased (p <
      0.05) in the obese children compared to controls, while sclerostin was
      significantly decreased (24.67 +/- 10.06 vs. 30.42 +/- 11.01 pmol/L, p < 0.05).
      P1NP was also significantly increased (p < 0.01). PTH was negatively correlated
      with TCSA, CA, and BBRI. Bone turnover is higher in obese children than in
      controls, and this is associated with smaller and apparently weaker bones. Higher
      PTH and lower sclerostin levels may be responsible for these findings.

PMID- 24687527
TI  - Prostatic ductal adenocarcinoma: an aggressive tumour variant unrecognized on T2
      weighted magnetic resonance imaging (MRI).
AB  - INTRODUCTION: Prostatic ductal adenocarcinoma (DCa) is an aggressive variant. The
      purpose of this study was to determine if T2 signal intensity (SI) differs from
      conventional adenocarcinoma (CCa). MATERIALS AND METHODS: A retrospective study
      of patients who underwent preoperative MRI and prostatectomy between 2009 and
      2012 was performed. T2 SI ratios (SIR) for tumour (T) to obturator internus
      muscle (M) and normal peripheral zone (PZ) were compared. Two radiologists
      evaluated the central gland/PZ to detect tumours and compared diagnostic
      accuracy. RESULTS: T2 SIR for DCa were 3.60 (T/M), 0.66 (T/PZ); 2.68 (T/M), 0.47
      (T/PZ) for Gleason 9; 2.50 (T/M), 0.47 (T/PZ) for Gleason 7/8 and 3.95 (T/M),
      0.73 (T/PZ) for Gleason 6 tumours. There was a difference in T2 T/M and T/PZ SIR
      between DCa and Gleason 9 (p = 0.003, p = 0.004) and Gleason 7/8 (p = 0.006, p =
      0.002), but no difference in SIR between DCa and Gleason 6 tumours. The
      sensitivity for tumour detection was 0-27 % for DCa, 64-82 % for Gleason 9, 44-88
      % for Gleason 7-8 and 0-20 % for Gleason 6. There was a difference in the
      sensitivity of detecting Gleason 9 and 7/8 tumours when compared to DCa (p =
      0.004, p = 0.001). CONCLUSIONS: DCa resembles Gleason score 6 tumour at T2
      weighted MRI, which underestimates tumour grade and renders the tumour occult.
      KEY POINTS: Prostatic ductal adenocarcinoma is aggressive, resembling endometrial
      carcinoma at histopathology. Prostatic ductal adenocarcinoma resembles Gleason
      score 6 tumour at T2-weighted MRI. MRI grading may underestimate ductal
      adenocarcinoma based on increased T2 signal.

PMID- 24687528
TI  - Leukemia inhibitory factor enhances bovine oocyte maturation and early embryo
      development.
AB  - The present study was conducted to examine the effects of leukemia inhibitory
      factor (LIF) on bovine oocyte maturation and early embryo development in vitro.
      Results showed that LIF supplementation (25 ng/ml) enhanced nuclear maturation of
      intact cumulus-oocyte complexes (COCs) compared to the vehicle control. Similar
      results were observed in denuded oocytes, indicating that LIF directly influences
      oocyte development. LIF-treated oocytes showed a higher cortical-granule
      migration rate and increased expression of CD9, a tetraspanin transmembrane
      protein essential for fertilization. After in vitro fertilization, oocytes
      receiving LIF supplementation exhibited a higher cleavage rate and yielded a
      significantly higher number of blastocysts. To further dissect the molecular
      mechanism underlying this LIF-induced bovine oocyte maturation phenotype, we
      examined the involvement of two signaling cascades, mitogen-activated protein
      kinases (MAPK3/1)- and the signal transducer and activator of transcription 3
      (STAT3)-dependent pathways. Western blot results revealed that LIF phosphorylated
      MAPK3/1 and STAT3. Inhibition of MAPK3/1 activation with MEK inhibitor U0126 only
      partially blocked LIF-induced nuclear maturation, although it attenuated oocyte
      cytoplasmic maturation. Inhibition of JAK/STAT3 activation with a specific
      pharmacological inhibitor completely abolished the LIF-response in bovine oocyte.
      In summary, these data revealed a novel role for LIF in bovine oocyte maturation
      subsequent embryonic development.

PMID- 24687529
TI  - Single-shot imaging with higher-dimensional encoding using magnetic field
      monitoring and concomitant field correction.
AB  - PURPOSE: PatLoc (Parallel Imaging Technique using Localized Gradients)
      accelerates imaging and introduces a resolution variation across the field-of
      view. Higher-dimensional encoding employs more spatial encoding magnetic fields
      (SEMs) than the corresponding image dimensionality requires, e.g. by applying two
      quadratic and two linear spatial encoding magnetic fields to reconstruct a 2D
      image. Images acquired with higher-dimensional single-shot trajectories can
      exhibit strong artifacts and geometric distortions. In this work, the source of
      these artifacts is analyzed and a reliable correction strategy is derived.
      METHODS: A dynamic field camera was built for encoding field calibration.
      Concomitant fields of linear and nonlinear spatial encoding magnetic fields were
      analyzed. A combined basis consisting of spherical harmonics and concomitant
      terms was proposed and used for encoding field calibration and image
      reconstruction. RESULTS: A good agreement between the analytical solution for the
      concomitant fields and the magnetic field simulations of the custom-built PatLoc
      SEM coil was observed. Substantial image quality improvements were obtained using
      a dynamic field camera for encoding field calibration combined with the proposed
      combined basis. CONCLUSION: The importance of trajectory calibration for single
      shot higher-dimensional encoding is demonstrated using the combined basis
      including spherical harmonics and concomitant terms, which treats the concomitant
      fields as an integral part of the encoding.

PMID- 24687531
TI  - Combination chemotherapy of low-dose 5-fluorouracil and cisplatin for advanced
      extramammary Paget's disease.
AB  - BACKGROUND: Extramammary Paget's disease (EPD) is a cutaneous adenocarcinoma. It
      is usually curable by wide local excision. However, the prognosis for EPD
      patients with metastases is extremely poor because effective chemotherapy for
      advanced EPD has not been established. METHODS: We retrospectively analyzed the
      efficacy of combination chemotherapy consisting of infusions of 5-fluorouracil (5
      FU, 600 mg/m(2)/body, 5 days/week) and cisplatin (5-10 mg/body, 5-7 days/week)
      administered intravenously for 8-24 h (low-dose FP). RESULTS: The patients were
      15 males and 7 females and the ages ranged from 54 to 91 years old (median 71).
      The toxicities of low-dose FP were as follows: hematopoietic dysfunction (n = 4),
      gastrointestinal dysfunction (4), nephropathy (1), and phlebitis (1). Almost all
      toxicities were grade 1 or 2 except for 2 cases with grade 3 leukopenia or
      pancytopenia. Seventeen patients were treated with low-dose FP only, and the
      clinical results included 10 partial responses (PR), 4 stable disease (SD), and 3
      progressive disease (PD). The overall survival ranges (medians) were 5-51 months
      (12) in all 22 patients, 6-51 months (13) in the 13 patients showing complete
      response or PR, and 5-12 months (11) in the 6 SD patients. The reported
      palliative effects of low-dose FP include control of pain and improvement of
      lymphedema. CONCLUSION: Although the number of cases is limited and there is a
      bias because cases without clinical effects are less likely to be reported, this
      regimen might be considered a relatively effective option for advanced EPD.

PMID- 24687530
TI  - Role of sentinel lymph node biopsy in patients with Merkel cell carcinoma:
      statistical analysis of 403 reported cases.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with a
      high rate of nodal metastasis. Sentinel lymph node biopsy (SLNB) is used in MCC
      and other cancers to identify regional node micrometastases in patients with
      clinically negative nodes; however, whether SLN status is associated with
      recurrence or prognosis in MCC is unclear. METHODS: A statistical analysis was
      performed of 397 published cases of MCC with SLNB results from 22 reports and 6
      new cases, in order to elucidate any correlation between SLN status and
      recurrence, and to determine false-negative rates for SLNB. RESULTS: Of these 403
      cases, 128 (31.8 %) had positive SLNs; 16 of these 128 (12.5 %) developed
      recurrence (6 nodal, 10 distant). Of 275 patients with negative SLNs, 27 (9.8 %)
      developed recurrence (19 nodal, 8 distant). Patients with positive SLNs had a
      greater risk of distant metastasis (OR 2.82; P = 0.037; 95 % CI 1.089-7.347). The
      false-negative rate for SLNB in all 403 patients was 12.9 %. Use of the
      immunohistochemical approach to diagnosis of micrometastasis with anti-CK20
      antibody did not affect the false-negative rate. CONCLUSIONS: Patients with
      positive SLNs had a greater risk of distant metastasis in MCC; positive SLN was
      an important prognostic factor in MCC. Further studies using standardized, more
      sensitive techniques to examine entire SLNs may decrease the false-negative rate,
      and improve the significance of SLNB in MCC.

PMID- 24687533
TI  - Concordance between prenatal ultrasound and autopsy findings in a tertiary
      center.
AB  - OBJECTIVE: The aim of this study was to evaluate the ultrasound (US)/autopsy
      concordance in elective termination of pregnancies (TOP) due to fetal causes.
      METHODS: We performed a retrospective evaluation of elective TOP from 2004 to
      2012. Inclusion criteria were gestational age at termination <24 weeks, fetal
      pathology and availability of US/autopsy data. Based on the US-autopsy
      concordance, cases were divided into four groups: Group 1: agreement; Group 2:
      autopsy confirmed all US findings but provided additional information; Group 3:
      autopsy didn't confirm all US findings; Group 4: disagreement. RESULTS: One
      hundred and fifty-one patients fulfilled the inclusion criteria during the study
      period. Central nervous system malformations (91.5%), cardiovascular anomalies
      (90.2%) and renal system malformations (91.3%) were confirmed by autopsy. We
      found less concordance in the abdominal and musculoskeletal anomalies (61.5% and
      66.7%, respectively). There were 130 (86%) fetuses in group 1, 7 in group 2
      (4.6%), 3 in group 3 (1.9%) and 11 in group 4 (7.2%). In 5.29% of cases, the
      autopsy added relevant information to the diagnosis and counselling. CONCLUSIONS:
      Diagnosis concordance between US and necropsy is achieved in almost 90% of cases.
      An autopsy may help to adjust the diagnosis and help in counselling the parents
      for a future pregnancy.

PMID- 24687534
TI  - Structural characteristics that stabilize or destabilize different assembly
      levels of phycocyanin by urea.
AB  - Phycocyanin is one of the two phycobiliproteins always found in the Phycobilisome
      antenna complex. It is always situated at the ends of the peripheral rods,
      adjacent to the core cylinders composed of allophycocyanin. The basic phycocyanin
      monomer is an (alphabeta) dimer of globin-like subunits with three covalently
      linked phycocyanobilin cofactors. Monomers assemble further into trimers,
      hexamers, and rods which include non-pigmented linker proteins. Upon isolation in
      low ionic strength solution, rods quickly disintegrate into phycocyanin trimers,
      which lose contacts with other phycobiliproteins and with the linker proteins.
      The trimers, however, are quite stable and only the presence of high
      concentrations of chaotropic agents (such as urea), very acidic solutions, or
      elevated temperatures induces monomerization, followed by separation between the
      subunits. We have recently determined the crystal structures of phycocyanin from
      the thremophilic cyanobacterium Thermosynechococcus vulcanus in the presence of 2
      or 4 M urea, and shown that 4 M urea monomerizes the phycocyanin trimers. In this
      paper, we will describe the phycocyanin structures in 2 and 4 M urea more
      completely. By mapping out the urea positions, we describe the structural
      elements within the trimeric interaction interface that may be interrupted by the
      presence of 4 M urea. In addition, we also identify what are the structural
      characteristics that prevent 4 M urea from inducing subunit dissociation. 

PMID- 24687535
TI  - Relation of the rs6923761 gene variant in glucagon-like peptide 1 receptor with
      weight, cardiovascular risk factor, and serum adipokine levels in obese female
      subjects.
AB  - BACKGROUND: Studies of the glucagon-like peptide 1 (GLP-1) receptor have been
      directed at identifying polymorphisms in the GLP-1 receptor gene that may be a
      contributing factor in the pathogenesis of diabetes mellitus and cardiovascular
      risk factors. Nevertheless, the role of GLP-1 variants on body weight,
      cardiovascular risk factors, and adipokines remains unclear in obese patients.
      OBJECTIVE: Our aim was to analyze the effects of rs6923761 GLP-1 receptor
      polymorphism on body weight, cardiovascular risk factors, and serum adipokine
      levels in nondiabetic obese females. DESIGN: A sample of 645 obese nondiabetic
      Caucasian females was enrolled in a prospective way. Basal fasting glucose, c
      reactive protein (CRP), insulin, insulin resistance (homeostasis model assessment
      (HOMA)), total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides
      concentration, and adipokines were measured. Weights, body mass index (BMI),
      waist circumference, fat mass by bioimpedance, and blood pressure measures were
      measured. RESULTS: Three hundred and twenty-seven participants (50.7%) had the
      genotype GG and 318 (49.3%) study subjects had the next genotypes; GA (270 study
      subjects, 41.9%) or AA (48 study subjects, 7.4%) (second group). In wild group
      (GG genotype), BMI (1.8 +/- 2.3 kg/m(2) ; P < 0.05), weight (3.1 +/- 1.3 kg; P <
      0.05), fat mass (2.4 +/- 1.1 kg; P < 0.05), waist circumference (2.7 +/- 1.9 cm;
      P < 0.05), triglyceride levels (10.4 +/- 5.3 mg/dl; P < 0.05), interleukin 6 (IL
      6) (1.5 +/- 0.9 ng/dl; P < 0.05), resistin (1.1 +/- 0.3 ng/dl; P < 0.05), and
      leptin (30.1 +/- 10.3 ng/dl; P < 0.05) levels were higher than mutant group (GA +
      AA). CONCLUSION: Data from our study revealed an association with decreased
      metabolic and cardiovascular markers in obese females. BMI weight, fat mass,
      waist circumference, triglycerides, leptin, resistin, and IL-6 serum levels were
      lower in subjects with A allele than non-A allele subjects.

PMID- 24687536
TI  - Dyadic influence of hope and optimism on patient marital satisfaction among
      couples with advanced breast cancer.
AB  - PURPOSE: An estimated 10-40 % of breast cancer (BC) patients report negative
      changes to their partnered relationships. Literature suggests that for these
      patients, marital satisfaction is related to depression and other quality of life
      factors which are associated with survivorship and treatment response. However,
      existing literature does not provide a clear explanation of the factors that
      strengthen vs. create strain in couples facing cancer. Given the benefits of a
      satisfying relationship to patient quality of life, it is important to better
      understand factors that put patients at greater risk for marital difficulties.
      This study examined the differential and combined roles of hope and optimism
      among BC patients and their partners on patient marital satisfaction. METHOD:
      Fifty-six breast cancer patient-partner dyads completed study questionnaires as
      part of a larger study. Regression analyses were used to examine the main and
      interaction effects of patient and partner hope and optimism on patient marital
      satisfaction. RESULTS AND CONCLUSION: Higher patient and partner hope predicted
      greater patient marital satisfaction, whereas optimism did not. These results are
      divergent from the literature on optimism and well-being, which shows the
      importance of studying these two traits concurrently. Interaction effects suggest
      certain combinations of patient and partner hope and optimism are more beneficial
      than others for patient marital satisfaction and suggest a dyadic approach is
      important for investigation of well-being in breast cancer.

PMID- 24687537
TI  - Weight loss and body mass index in relation to aspiration in patients treated for
      head and neck cancer: a long-term follow-up.
AB  - PURPOSE: Persistent severe swallowing dysfunction with aspiration is a common and
      sometimes overlooked sequelae after treatment for squamous cell carcinoma of the
      head and neck (SCCHN) and may impact food intake and nutritional status. More
      knowledge is needed to increase the understanding of severe swallowing
      dysfunction as a risk factor for persistent nutritional deteriorations in SCCHN
      survivors. The purpose of the study was to investigate weight loss and body mass
      index (BMI) in relation to pharyngeal swallowing function in a long-term
      perspective in patients after SCCHN treatment. METHODS: Data from 101 patients
      were available for the analyses. Swallowing function was assessed by
      videofluoroscopy at a mean of 71.6 months after the start of radiotherapy (RT).
      Percent weight change (calculated with weight at the start of RT as the
      reference) and BMI at follow-up were the primary nutritional measures. RESULTS:
      Aspiration was present in 48 of 101 patients (48 %). Patients with aspiration had
      a significantly higher mean weight loss and a lower BMI (-10.9 % and 23.1,
      respectively) at follow-up compared with patients without aspiration (-2.8 % and
      26.0, respectively). Patients with aspiration were unable to gain weight after 23
      months. Only ten of 101 patients (10 %) were underweight at follow-up.
      CONCLUSIONS: Swallowing dysfunction with aspiration was related to long-term
      weight loss and reduced BMI. Few patients were underweight despite the high
      prevalence of swallowing dysfunction.

PMID- 24687538
TI  - Automated monitoring of symptoms during ambulatory chemotherapy and oncology
      providers' use of the information: a randomized controlled clinical trial.
AB  - PURPOSE: Monitoring patient-reported symptoms is necessary to adjust and improve
      supportive care during chemotherapy. Continuing advances in computerized
      approaches to symptom monitoring can enhance communication about unrelieved
      symptoms between patients and oncology providers and may facilitate intensified
      symptom treatment. METHODS: An automated IT-based telephone monitoring system was
      developed to enable oncology providers to receive and act on alert reports from
      patients about unrelieved symptoms during chemotherapy treatment. Daily, 250
      participants (randomized to treatment or attentional control) were asked to call
      the automated system to report presence, severity, and distress for common
      chemotherapy-related symptoms (1-10 scale if present). For the treatment group,
      symptoms exceeding preset thresholds for moderate-to-severe intensity levels
      generated emailed alert reports to both the patient's oncologist and oncology
      nurse. RESULTS: Patients reported high satisfaction and ease of use of the
      automated system. Over 80 % of providers reported usefulness of the symptom alert
      reports. Ten monitored symptoms resulted in, on average, nine moderate-to-severe
      intensity alerts per patient over 45 study days. However, providers rarely
      contacted patients after receiving alerts. There were no significant differences
      in change of symptom severity between the two groups (mean difference = 0.06, p =
      0.58). CONCLUSION: Despite patients' use of a daily symptom monitoring system and
      providers' receipt of information about unrelieved symptoms of moderate-to-severe
      intensity, oncology physicians and nurses did not contact patients to intensify
      symptom treatment nor did symptoms improve. Further research is indicated to
      determine if oncology providers initiated follow-up to intensify symptom
      treatment, whether symptom outcomes would improve.

PMID- 24687539
TI  - Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative
      cohort study to explore the influence of patient-reported outcomes on therapy
      decisions.
AB  - PURPOSE: Optimal long-lasting treatment with sunitinib and sorafenib is limited
      by dose modifications (DMs) due to adverse events (AEs). These AEs may be
      underrecognized and their influence on health-related quality of life (HRQL)
      underestimated. Improved insight into the relationship between AEs and therapy
      decisions is needed. To improve decision making around managing symptoms and
      reduce DMs, this study was set up to explore the influence of patient-reported
      symptoms on therapy decisions. METHODS: In this multicenter cohort study, patient
      characteristics, reasons for and different forms of used dose modifications, and
      AEs were prospectively obtained from cancer patients on sunitinib/sorafenib
      treatment. Used instruments to get insight into AEs were the patient-scored
      Utrecht Symptom Diary (USD) and the professional-scored Common Terminology
      Criteria for AEs version 3.0. RESULTS: Median total treatment duration in 42
      patients was 16 weeks. Median time till dose modification was 10 weeks. DMs
      occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence
      of most AEs was found compared to the literature. Sixty percent of the patients
      experienced a decreased HRQL due to multiple AEs. CONCLUSIONS: Because severe AEs
      due to sunitinib/sorafenib treatment seldom occur, it is more important to focus
      on treating and preventing multiple mild AEs with higher impact on HRQL, when
      trying to avoid dose modifications. Using patient self-reported measurement
      methods helps to early recognize symptoms and to differentiate among symptom
      intensities. This systematic approach might help to achieve the optimal dosing,
      which might improve PFS and OS.

PMID- 24687540
TI  - Human endometrial stem cells differentiation into functional hepatocyte-like
      cells.
AB  - In spite of certain clinical limitations, such as teratoma formation, the use of
      stem cells is considered as an appropriate source in cell therapy and tissue
      engineering. This study shows human endometrial stem cells (hEnSCs) has
      exceptional differentiation ability in hepatocyte formation. hEnSCs have high
      purification rate and immune-tolerance, and can be used as an appropriate
      substitute for hepatocytes in liver disorders. Differentiation required
      hepatogenic medium. Quantitative reverse transcription-polymerase chain reaction
      and immunofluorescent staining of hepatic genes and proteins including
      cytokeratin 18 (ck18), alpha-fetoprotein (afp), and albumin (alb) were used to
      assess differentiation. Cells differentiated with a hepatocyte-like morphology
      and expressed hepatic markers on 30 days of differentiation. The Periodic Acid
      Schiff (PAS) reaction showed storage of glycogen, and albumin and afp secretions
      were also detected. In vitro hEnSCs behave like hepatocyte after differentiation
      and may be a suitable source of cells in liver regeneration. 

PMID- 24687541
TI  - Chronic Digoxin Toxicity Precipitated by Dronedarone.
AB  - OBJECTIVE: To report the case of a patient who presented with chronic symptoms
      attributable to dronedarone-induced digoxin toxicity. A review of the literature
      is also provided. CASE SUMMARY: This case report details a case of a 77-year-old
      male patient who presented to the hospital with multiple ambiguous symptoms that
      lasted several weeks. The patient was later hospitalized for symptoms of chronic
      digoxin toxicity, including prolonged nausea, diarrhea, weakness, and lack of
      appetite. The patient had a long history of digoxin use for control of his atrial
      fibrillation but experienced signs and symptoms of toxicity only after the
      addition of dronedarone. DISCUSSION: Both the Naranjo and Drug Interaction
      Probability Scales indicated a "probable" relationship between the development of
      digoxin toxicity and dronedarone. Due to a p-glycoprotein-mediated interaction,
      dronedarone is able to decrease the renal clearance of digoxin, thus putting
      patients at risk for potentially fatal digoxin toxicity. CONCLUSION: This is the
      second case report detailing dronedarone-induced digoxin toxicity and the first
      to focus on chronic digoxin toxicity. The presentation, possible causes, and drug
      drug interactions associated with digoxin toxicity are described. This report
      aims to increase clinicians' awareness of this possible complication. It is
      recommended that digoxin be discontinued prior to initiating dronedarone. If
      concomitant therapy is absolutely necessary, the dose of digoxin should be halved
      prior to initiating dronedarone. Digoxin plasma levels should be monitored
      closely, with frequent patient evaluation for signs and symptoms of digoxin
      toxicity.

PMID- 24687542
TI  - beta-blockers: a review of their pharmacological and physiological diversity in
      hypertension.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, and pharmacodynamic
      properties of commonly used beta-blockers (atenolol, carvedilol, metoprolol
      succinate, metoprolol tartrate, and nebivolol). DATA SOURCES: A MEDLINE
      literature search (1966-May 2013) was performed using the following key terms:
      hypertension, beta-blockers, atenolol, carvedilol, metoprolol tartrate,
      metoprolol succinate, nebivolol, pharmacology, pharmacodynamics,
      pharmacokinetics, blood pressure, metabolic, lipid, central aortic pressure,
      diabetes, and insulin resistance. References from publications reviewed were
      included. STUDY SELECTION AND DATA EXTRACTION: English-language articles
      identified were reviewed. Animal studies and studies in patients for a primary
      diagnosis of coronary artery disease were excluded. DATA SYNTHESIS: beta-Blockers
      are no longer recommended first-line therapy for primary hypertension, based on
      data showing that beta-blockers are inferior to other antihypertensives and no
      better than placebo, in spite of provision of blood pressure reduction. Because
      atenolol is the beta-blocker used in 75% of these studies, uncertainty about
      widespread application to all beta-blockers exists. Different pharmacological and
      physiological properties, both within beta-blockers and compared with other
      antihypertensives, may explain divergent effects. Evidence shows that beta
      blockers have a truncated effect on central aortic pressure, an independent
      predictor of cardiovascular events, compared with other antihypertensive classes;
      differences within the class may exist, but the evidence is inconclusive.
      Metabolic effects differ within the beta-blocker class, with evidence that
      carvedilol causes less metabolic dysregulation. CONCLUSION: Emerging evidence
      reveals physiological differences within the beta-blocker class and in comparison
      to other antihypertensives. These differences provide insight into the diverse
      clinical effects beta-blockers provide in cardiovascular disease.

PMID- 24687543
TI  - Propylene Glycol-Related Delirium After Esmolol Infusion.
AB  - OBJECTIVE: Excipients used in oral or intravenous preparations may cause serious
      adverse events. CASE SUMMARY: We present the case of a 15-year-old boy with
      hypertrophic cardiomyopathy. In the pediatric intensive care unit, he received
      high doses of continuous intravenous esmolol (range = 20-400 ug/kg/min) for
      cardiac rhythm control. After a few days he developed a delirium not responding
      to high doses of antipsychotics or discontinuation of benzodiazepines. We
      eventually realized that the IV esmolol formulation contained high doses of
      propylene glycol and ethanol, which may accumulate after prolonged infusion and
      cause intoxication. Intoxication with propylene glycolcan cause neuropsychiatric
      symptoms. The boy's propylene glycol plasma concentration was approximately 4
      g/L, whereas clinical symptoms arise at concentrations above 1 to 1.44 g/L.
      Application of the Naranjo adverse drug reaction probability scale suggested a
      probable relationship (score 6) between the propylene glycol infusion and the
      delirium. After discontinuation of esmolol, the delirium disappeared
      spontaneously. DISCUSSION: This is the first case describing excipient toxicity
      of esmolol, with an objective causality assessment revealing a probable
      relationship for the adverse event-namely, delirium-and esmolol. CONCLUSION:
      Although excipient toxicity is a well-known adverse drug reaction, this case
      stresses the importance for easily available information for and education of
      physicians.

PMID- 24687544
TI  - Moxifloxacin-Induced Immune-Mediated Thrombocytopenia in a Chronic Kidney Disease
      Patient Receiving Hemodialysis.
AB  - OBJECTIVE: To alert clinicians to a serious complication from a commonly
      prescribed medication, moxifloxacin. CASE SUMMARY: A 65-year-old male, septic,
      hemodialysis patient developed thrombocytopenia following exposure to vancomycin,
      ceftazidime, and moxifloxacin. Drug-specific immunoglobulin testing showed
      positive autoantibodies against only moxifloxacin, and the probability
      stratification proposed by Naranjo et al would give this case a score of 7-a
      probable association between moxifloxacin and the adverse event. DISCUSSION:
      Idiopathic thrombocytopenic purpura (ITP) results in immune-mediated platelet
      destruction, with bleeding risk frequently manifested by purpuric skin and
      mucosal lesions. Although many drugs are associated with ITP, moxifloxacin has
      only been characterized in 2 previous case reports. This is the first case report
      where specific immunoglobulin antibody testing showed a positive association
      between ITP and moxifloxacin. CONCLUSIONS: Moxifloxacin is a commonly prescribed
      medication because of its wide spectrum of activity, high bioavailability, and
      convenient dose schedule. Clinicians need to be aware of this little-known side
      effect of this commonly prescribed antibiotic.

PMID- 24687545
TI  - Clinical practice patterns in hospitalized patients at risk for invasive
      candidiasis: role of antifungal stewardship programs in an era of rapid
      diagnostics.
AB  - BACKGROUND: Rapid diagnostic tests for Candida are becoming available that may
      supplement traditional microbiological identification. OBJECTIVE: Assess clinical
      practice patterns in patients with or at risk of candidiasis who may benefit from
      the use of rapid diagnostic tests. METHODS: This was a prospective cohort study
      of patients with candidemia or receiving systemic antifungals conducted at a
      university-affiliated tertiary care hospital. Time to initiation of therapy,
      Candida species, time to identification, and indications for antifungal use were
      assessed. RESULTS: A total of 162 patients with candidemia aged 58 +/- 17 years
      were identified. Average time to yeast identification yeast was 2.2 +/- 1.3 days
      and varied by Candida species (range = 0.6-7.9 days). Average time for patient to
      start antifungal therapy was 3.5 +/- 2.1 days. In Monte Carlo simulations,
      average time to initiation of antifungal therapy was 0.6 +/- 0.2 days for
      T2Candida, 2.6 +/- 1.3 days for PNA-FISH (fluorescence in situ hybridization
      using peptide nucleic acid probes), and 2.5 +/- 1.4 days for MALDI-TOF (matrix
      assisted laser desorption/ionization time of flight). Use of T2Candida on the day
      of the blood culture collection resulted in 3136 to 6078 fewer doses of
      echinocandins annually per 5000 patients. CONCLUSION: Many interventions are
      possible for antifungal stewardship programs to improve care of patients at risk
      for systemic candidiasis, including rapid identification of yeast species and
      limiting unnecessary antifungal agents. Technology enabling rapid diagnosis of
      Candida will be paramount to appropriate, cost-effective treatment of patients
      with or at risk for candidiasis.

PMID- 24687546
TI  - Ultraweak, spontaneous photon emission in seedlings: toxicological and
      chronobiological applications.
AB  - The detection of ultraweak light emission in seedlings has been explored in
      toxicological and chronobiological studies. The main studies in this area are
      reviewed briefly, including a report on applied tests held in the last 7 years at
      LaFA--UNICAMP (Brazil). In general, results indicate that a linear relation for
      total light emission versus germination performance is found if only strong
      stress situations are considered, when external factors depress a seedling's
      development, even when considering a sequential series of tests. Light emitted by
      a single seedling was detected in a compact apparatus, and data are presented
      here for the first time showing pronounced circadian cycles are evident, with
      similar time and frequency profiles as those of the local gravimetric tide.

PMID- 24687548
TI  - Engineering DNA binding sites to assemble and tune plasmonic nanostructures.

PMID- 24687547
TI  - Hydrothermal fabrication of hydroxyapatite/chitosan/carbon porous scaffolds for
      bone tissue engineering.
AB  - Porous carbon fiber felts (PCFFs) have great applications in orthopedic surgery
      because of the strong mechanical strength, low density, high stability, and
      porous structure, but they are biologically inert. To improve their biological
      properties, we developed, for the first time, the hydroxyapatite
      (HA)/chitosan/carbon porous scaffolds (HCCPs). HA/chitosan nanohybrid coatings
      have been fabricated on PCFFs according to the following stages: (i) deposition
      of chitosan/calcium phosphate precursors on PCFFs; and (ii) hydrothermal
      transformation of the calcium phosphate precursors in chitosan matrix into HA
      nanocrystals. The scanning electron microscopy images indicate that PCFFs are
      uniformly covered with elongated HA nanoplates and chitosan, and the macropores
      in PCFFs still remain. Interestingly, the calcium-deficient HA crystals exist as
      plate-like shapes with thickness of 10-18 nm, width of 30-40 nm, and length of 80
      120 nm, which are similar to the biological apatite. The HA in HCCPs is similar
      to the mineral of natural bone in chemical composition, crystallinity, and
      morphology. As compared with PCFFs, HCCPs exhibit higher in vitro bioactivity and
      biocompatibility because of the presence of the HA/chitosan nanohybrid coatings.
      HCCPs not only promote the formation of bone-like apatite in simulated body
      fluid, but also improve the adhesion, spreading, and proliferation of human bone
      marrow stromal cells. Hence, HCCPs have great potentials as scaffold materials
      for bone tissue engineering and implantation.

PMID- 24687549
TI  - CCL5-403, CCR5-59029, and Delta32 polymorphisms and cancer risk: a meta-analysis
      based on 20,625 subjects.
AB  - Associations between CCL5-403, CCR5-59029, and Delta32 polymorphisms and cancer
      risk are inconclusive. To derive a more precise estimation of the association, we
      performed a meta-analysis by searching PubMed, EMBASE, Google scholar, and
      WanFang databases. A total of 20 eligible articles with 39 studies were included.
      Of those studies, there were 21 studies for CCR5-Delta32 polymorphism, 9 studies
      for CCR5-59029 polymorphism, and 9 studies for CCL5-403 polymorphism. Combined
      analysis revealed no associations between these polymorphisms and cancer risk.
      However, subgroup analysis by ethnicity suggested that CCR5-59029 polymorphism
      was associated with the risk of cancer among Asian populations (A vs. G: odds
      ratio (OR)=1.36, 95 % confidence interval (CI) 1.13-1.65, P H=0.27; AA vs. GG:
      OR=2.07, 95 % CI 1.37-3.12, P H=0.17; GA+AA vs. GG: OR=1.35, 95 % CI 1.03-1.77, P
      H=0.92; AA vs. GA+GG: OR=1.98, 95 % CI 1.01-3.88, P H=0.08), but not among
      Caucasian populations. CCL5-403 polymorphism was associated with the risk of
      cancer among African populations (A vs. G: OR=0.68, 95 % CI 0.55-0.83, P H=0.14;
      AA vs. GG: OR=0.51, 95 % CI 0.33-0.77, P H=0.52; AG vs. GG: OR=0.58, 95 % CI 0.42
      0.80, P H=0.14; AG+AA vs. GG: OR=0.56, 95 % CI 0.41-0.75, P H=0.13), but not
      among Caucasian populations and Asian populations. Overall, this meta-analysis
      indicated that CCR5-Delta32 was not associated with the risk of cancer. CCR5
      59029 polymorphism contributed to cancer risk among Asian populations, and CCL5
      403 polymorphism was associated with the decreased risk of cancer among African
      populations.

PMID- 24687550
TI  - The expression and clinical significance of high mobility group nucleosome
      binding domain 5 in human osteosarcoma.
AB  - The high mobility group nucleosome binding domain 5 (HMGN5) is a member of the
      high mobility group proteins family and highly expressed in multiple
      malignancies. Nevertheless, the role of HMGN5 in osteosarcoma remains unclear.
      This study aimed to investigate the expression and clinical significance of HMGN5
      in human osteosarcoma, confirm the oncogenic role of HMGN5 and explore the
      mechanism by which HMGN5 contributes to invasion and metastasis. HMGN5 expression
      was detected in osteosarcoma tissues and corresponding adjacent non-cancerous
      tissues (ANCTs) from 52 patients by immunohistochemical (IHC) assay and the
      clinicopathologic characteristics of all patients were also recorded. Next,
      osteosarcoma cells were transfected by HMGN5 RNA interference and cell viability,
      apoptosis and invasion were detected by cell vitality test, flow cytometry and
      transwell assay, respectively. As a result, IHC assay showed strong immunized
      activity of HMGN5 in the nucleus in all osteosarcoma tissues compared with the
      ANCT (53.5 +/- 4.3 % vs. 17.0 +/- 3.9 %, P < 0.01). HMGN5 expression level was
      associated with pathologic staging and TNM staging. Knockdown of HMGN5 induced
      cell cycle arrest, inhibited invasion and increased sensitivity to doxorubicin
      induced cell apoptosis in U2-OS and SaO2 cells. Western blot analysis
      demonstrated that there were increased expressions of cleaved caspase-3, cleaved
      PARP and decreased expressions of PCNA, PI3Kp85alpha, p-AKT, MMP-9, and cyclin B1
      in U2-OS and SaO2 cells depleted of HMGN5. HMGN5 plays oncogenic role in
      osteosarcoma by promoting cell proliferation and invasion, and could be exploited
      as a target for therapy in osteosarcoma.

PMID- 24687551
TI  - Development of a novel score for early detection of hepatocellular carcinoma
      among high-risk hepatitis C virus patients.
AB  - Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where
      effective therapies are lacking. Identification of new scoring system is needed
      to discriminate HCC patients from those with chronic liver disease. Based on the
      link between vascular endothelial growth factor (VEGF) and HCC progression, we
      aimed to develop a novel score based on combination of VEGF and routine
      laboratory tests for early prediction of HCC. VEGF was assayed for HCC group
      (123), liver cirrhosis group (210), and control group (50) by enzyme-linked
      immunosorbent assay (ELISA). Data from all groups were retrospectively analyzed
      including alpha-fetoprotein (AFP), international normalized ratio (INR), albumin
      and platelet count, transaminases, and age. Areas under receiving operating curve
      (ROC) were used to develop the score. A novel index named hepatocellular
      carcinoma-vascular endothelial growth factor score (HCC-VEGF score) = 1.26
      (numerical constant + 0.05 * AFP (U l(-1)) + 0.038 * VEGF (ng ml(-1)) + 0.004 *
      INR - 1.02 * albumin (g l(-1)) - 0.002 * platelet count * 10(9) l- (1) was
      developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating
      HCC patients from liver cirrhosis with sensitivity of 91 % and specificity of 82
      % at cutoff 4.4 (i.e., less than 4.4 considered cirrhosis and greater than 4.4
      considered HCC). Hepatocellular carcinoma-VEGF score could replace AFP in HCC
      screening and follow up of cirrhotic patients.

PMID- 24687552
TI  - IDO is highly expressed in breast cancer and breast cancer-derived circulating
      microvesicles and associated to aggressive types of tumors by in silico analysis.
AB  - Indoleamine-2,3-dioxygenase (IDO) has been established as a normal mechanism of
      peripheral tolerance and immunosuppression. Besides, malignant tumors release
      microvesicles (MV) related with tumor dissemination. The aims of this study were
      to determine the expression of IDO in breast cancer and circulating microvesicles
      from breast cancer patients and to perform an in silico analysis to find genes co
      expressed to IDO. One hundred and twenty-two tissue and serum breast samples (91
      malignant, 21 benign, and 10 normal), and MCF7, MDA-MB-231, and T47D breast
      cancer cell lines were included. Standard immunohistochemistry (IHC),
      immunocytochemistry (ICC), Western blot (WB), and RT-PCR were employed.
      Microvesicle isolation from plasma samples was obtained by serial centrifugation
      and ultracentrifugation. By IHC, 60 % breast cancer, 43 % benign, and 20 % normal
      samples were positive. Significant differences were found among normal, benign,
      and malignant samples. Breast cancer stages I, II, and III expressed IDO in 42,
      66, and 71 % of samples, respectively, while breast cancer cell lines also
      reacted; by WB, 9/25 microvesicles fractions showed bands at 42 kD. In silico
      analysis of IDO 1 gene expression in breast cancer showed its association with
      several genes related to immune response and apoptosis. Moreover, IDO and co
      expressed genes were found predominately in basal and erbB2 subtypes. The
      cumulative data indicate a high expression of IDO in breast cancer which
      increased with higher stages. Furthermore, IDO was found in association with
      circulating breast cancer MV, while experimental and in silico gene expression
      revealed that IDO was mainly expressed in a triple-negative subgroup.

PMID- 24687553
TI  - Evaluation of thyroid cancer in Chinese females with breast cancer by vascular
      endothelial growth factor (VEGF), microvessel density, and contrast-enhanced
      ultrasound (CEUS).
AB  - To evaluate thyroid cancer in Chinese females with breast cancer by VEGF, MVD,
      and contrast-enhanced ultrasound (CEUS), 34 of 2,278 female inpatients with
      breast diseases who underwent routine thyroid ultrasonography were pathologically
      proved as thyroid cancer and enrolled into two groups: a breast cancer group and
      a non-breast cancer group. CEUS was performed and enhancement patterns were
      classified. Time-intensity curve parameters were analyzed to correlate with MVD
      CD34 and VEGF expression. Fourteen (2.6 %) and 20 (1.1 %) patients in breast
      cancer and non-breast cancer group were pathologically diagnosed as thyroid
      cancer. Six (42.8 %) and 0(0 %) patients showed high enhancement CEUS patterns of
      thyroid cancer in these two groups, respectively. The arrival time of time
      intense curve was shorter, and the mean and peak intensity were higher in thyroid
      cancer in breast cancer group. The mean MVD counts and VEGF expression were
      significantly higher in thyroid and breast carcinomas in breast cancer group (P <
      0.01). We also found that the mean and peak intensity were significantly
      associated with MVD counts and VEGF expression (P < 0.01). CEUS is recommended in
      evaluating the microcirculation of thyroid cancer in women with breast cancer and
      has the significant relationship with MVD counts and VEGF expression.

PMID- 24687554
TI  - CYP17 polymorphism (rs743572) is associated with increased risk of gallbladder
      cancer in tobacco users.
AB  - Gallbladder cancer (GBC) involves interplay of sex steroids, including estrogen
      and progesterone. Since CYP17 is a key enzyme involved in estrogen and
      testosterone hormone biosynthesis as well as in xenobiotic metabolism, it may be
      a potential candidate gene in the carcinogenesis of the gallbladder. Hence, the
      present study aimed to investigate the association of CYP17 (rs2486758, and
      rs743572) polymorphisms with GBC susceptibility. The present study included a
      total of 414 histologically confirmed GBC and 230 healthy controls. The CYP17
      (rs2486758 and rs743572) polymorphisms were genotyped by TaqMan-Allele
      discrimination assays. Statistical analysis was performed by using SPSS ver. 16.
      Overall, both the CYP17 SNPs did not indicate any association with GBC risk at
      genotype, haplotype, or at the genotypic interaction levels. However, in the case
      only analysis, CYP rs743572 showed association with increased risk of GBC in
      tobacco users at hetero genotype and dominant models, as compared to non-user GBC
      patients. The TCrs2486758-AGrs743572 genotypic combination was also associated
      with increased GBC susceptibility in tobacco users. CYP17 rs743572 is associated
      with increased risk of GBC in tobacco users in the North Indian population.
      However, the study requires confirmation in other populations.

PMID- 24687556
TI  - Molecular and biochemical characteristics of recombinant beta-propeller phytase
      from Bacillus licheniformis strain PB-13 with potential application in aquafeed.
AB  - Phytic acid is the major storage form of organic phosphorus in nature- and plant
      based animal feed. It forms insoluble complexes with nutritionally important
      metals and proteins that are unavailable for monogastric or agastric animals.
      Phytases initiate the stepwise hydrolysis of phytic acid and release inorganic
      orthophosphate. In the present investigation, the phytase gene from a phytase
      producing Bacillus licheniformis strain PB-13 was successfully expressed in
      Escherichia coli BL21. Recombinant phytase 'rPhyPB13' was found to be
      catalytically active, with an activity of 0.97 U/mL and specific activity of 0.77
      U/mg. The rPhyPB13 was purified to 14.10-fold using affinity chromatography.
      Similar to other beta-propeller phytases, purified rPhyPB13 exhibited maximal
      activity at pH 6.0-6.5 and 60  degrees C in the presence of 1 mM Ca(2+) and was
      highly active over a wider pH range (pH 4.0-8.0) and high temperature (80 
      degrees C). It has shown maximum activity towards Na-phytate as substrate. The
      observed K m , V max and k cat of purified rPhyPB13 were 1.064 mM, 1.32
      MUmol/min/mg and 27.46 s(-1), respectively. PhyPB13 was resistant to trypsin
      inactivation, activated in presence of Ca(2+) and inhibited in presence of EDTA.
      Crude rPhyPB13 has good digestion efficiency for commercial feed and soybean
      meal. These results indicate that PhyPB13 is a beta-propeller phytase that has
      application potential in aquaculture feed.

PMID- 24687555
TI  - Global transcriptome analysis identifies regulated transcripts and pathways
      activated during oogenesis and early embryogenesis in Atlantic cod.
AB  - The molecular mechanisms underlying oogenesis and maternally controlled
      embryogenesis in fish are not fully understood, especially in marine species. Our
      aim was to study the egg and embryo transcriptome during oogenesis and early
      embryogenesis in Atlantic cod. Follicles from oogenesis stages (pre-, early-, and
      late-vitellogenic), ovulated eggs, and two embryonic stages (blastula, gastrula)
      were collected from broodstock fish and fertilized eggs. Gene expression profiles
      were measured in a 44 K oligo microarray consisting of 23,000 cod genes. Hundreds
      of differentially expressed genes (DEGs) were identified in the follicle stages
      investigated, implicating a continuous accumulation and degradation of
      polyadenylated transcripts throughout oogenesis. Very few DEGs were identified
      from ovulated egg to blastula, showing a more stable maternal RNA pool in early
      embryonic stages. The highest induction of expression was observed between
      blastula and gastrula, signifying the onset of zygotic transcription. During
      early vitellogenesis, several of the most upregulated genes are linked to nervous
      system signaling, suggesting increasing requirements for ovarian synaptic
      signaling to stimulate the rapid growth of oocytes. Highly upregulated genes
      during late vitellogenesis are linked to protein processing, fat metabolism,
      osmoregulation, and arrested meiosis. One of the genes with the highest
      upregulation in the ovulated egg is involved in oxidative phosphorylation,
      reflecting increased energy requirements during fertilization and the first rapid
      cell divisions of early embryogenesis. In conclusion, this study provides a large
      scale presentation of the Atlantic cod's maternally controlled transcriptome in
      ovarian follicles through oogenesis, ovulated eggs, and early embryos.

PMID- 24687557
TI  - Improved vitamin B12 fermentation process by adding rotenone to regulate the
      metabolism of Pseudomonas denitrificans.
AB  - Our previous research had revealed that the dissolved oxygen limitation was more
      favorable for vitamin B12 fermentation, due to its inducement to the increased
      glycolytic flux in Pseudomonas denitrificans. In this paper, a novel strategy was
      implemented to further investigate the metabolic characteristics of P.
      denitrificans under different oxygen supply levels, by exogenously adding
      rotenone (a respiratory chain inhibitor interfering with the oxygen consumption)
      to the fermentation broths. Compared to the fermentation process without rotenone
      treatment, it was observed that 5 mg/L rotenone treatment could significantly
      strengthen the glycolytic flux of P. denitrificans via activating the key
      glycolytic enzymes (phosphofructokinase and pyruvate kinase), resulting in the
      accelerated generations of anterior precursors (glutamate and 5-aminolevulinic
      acid) for vitamin B12 biosynthesis. Although 5 mg/L rotenone treatment had a
      negative effect on cell growth of P. denitrificans, the vitamin B12 yield was
      increased from 48.28 +/- 0.62 mg/L to 54.70 +/- 0.45 mg/L, which further proved
      that an increased glycolytic flux in P. denitrificans was a consequence of higher
      vitamin B12 production. 

PMID- 24687558
TI  - Periprosthetic supracondylar femoral fractures following total knee arthroplasty:
      clinical comparison and related complications of the femur plate system and
      retrograde-inserted supracondylar nail.
AB  - BACKGROUND: The purpose of this study is to analyze the clinical results and
      related complications of the femur plate system (FP) and the retrograde-inserted
      supracondylar nail (RISN). MATERIALS AND METHODS: The study included 42 cases of
      periprosthetic supracondylar femoral fractures (PSF) proximal to posterior
      stabilized total knee arthroplasty between 2005 and 2009. Twenty-four cases of
      PSF were treated with the FP, and the other 18 cases were treated with the RISN.
      This study cohort was divided into subgroups according to the AO classification.
      We retrospectively compared the clinical results between the FP and RISN group.
      RESULTS: There were no significant differences between the two groups in terms of
      time of clinical union (p = 0.649). In the subgroup analysis, the mean operation
      time was significantly different only in subgroup A1 (p = 0.03). Complications
      were seen in 29.2 % (7/24) of patients in the FP group and 27.8 % (5/18) in the
      RISN group. The age during the index TKA and fracture fixation was a significant
      risk (p = 0.008) factor for complications between the two groups. No significant
      differences were found in the other factors between the two groups. The p value
      for operative time (p = 0.223), immobilization period (p = 0.129), ROM (p =
      0.573), KSS (p = 0.379), KSS functional scores (p = 0.310) and time to union (p =
      0.649). CONCLUSION: Clinical results did not differ according to the treatment
      methods used. Fixation method and fracture type did not cause an increase in the
      complication rate, but there was a trend toward higher non-union rates with the
      FP method and higher re-fracture rate with the RISN method. Noting the fact that
      only increasing age correlated with an increased complication rate, more careful
      attention should be paid to elderly patients in terms of both prevention and
      surgical care. LEVEL OF EVIDENCE: Level III, therapeutic study.

PMID- 24687559
TI  - Plate osteosynthesis of fractures of the shaft of the humerus: comparison of
      limited contact dynamic compression plates and locking compression plates.
AB  - BACKGROUND: The aim of this retrospective study was to compare outcomes and
      complications of displaced fractures of the shaft of the humerus treated with
      limited-contact dynamic compression plates (LCDCPs) and locking compression
      plates (LCPs). MATERIALS AND METHODS: Two hundred and twelve patients with
      displaced fractures of the shaft of the humerus, treated with plate
      osteosynthesis from January 2005 to December 2009 were reviewed. One hundred and
      two patients (group A) were treated with LCDCP osteosynthesis and 110 patients
      (group B) were treated with LCP osteosynthesis. Clinical and radiological
      assessments were made at monthly intervals for the first 6 months and then at 2
      month intervals for the next 6 months. Primary outcome measures like operative
      time, duration of hospital stay, time to fracture union, union rate and secondary
      outcome measures (functional outcome and complications such as infection,
      malunion, delayed union, nonunion, implant failure and iatrogenic radial nerve
      palsy) were compared between both groups. The ULCA scoring system and Mayo elbow
      performance index (MEPI) were used to assess shoulder and elbow functions,
      respectively. Rodriguez-Merchan criteria were used to assess the functional
      outcomes of the fracture fixation. RESULTS: There was no significant difference
      found between the two groups in terms of primary outcome measures. According to
      Rodriguez-Merchan criteria, comparison of functional outcomes of both groups
      showed insignificant difference (p = 0.48). There was no significant difference
      found between the two groups regarding mean ULCA score (p = 0.34) and mean MEPI
      sore (p = 0.54). In terms of complications, no significant difference was found
      between the two groups. CONCLUSION: This study concludes that the principle of
      fracture fixation was more important than plate selection in fractures of the
      shaft of the humerus. LEVEL OF EVIDENCE: Level 3.

PMID- 24687560
TI  - Hybrid epicardial and endocardial ablation of a persistent atrial tachycardia
      arising from the marshall bundle: the importance of a detailed analysis of the
      local potentials.
AB  - Radiofrequency catheter ablation of an atrial tachycardia (AT) and atrial
      fibrillation (AF) was performed in a patient with a history of pulmonary vein
      isolation for paroxysmal AF. The AT exhibited a centrifugal pattern with the
      posterolateral LA as the earliest activation site. The AT was not terminated by
      ablation at the endocardial earliest site, but its cycle length was prolonged by
      ablation at an opposite site within the Vein of Marshall. Finally, the AT was
      terminated by an energy application at a site 7 mm posteroinferior to the initial
      earliest activation site. We analyzed the local potentials of each energy
      delivery site in detail. 

PMID- 24687561
TI  - Covariance adjustment for batch effect in gene expression data.
AB  - Batch bias has been found in many microarray gene expression studies that involve
      multiple batches of samples. A serious batch effect can alter not only the
      distribution of individual genes but also the inter-gene relationships. Even
      though some efforts have been made to remove such bias, there has been relatively
      less development on a multivariate approach, mainly because of the analytical
      difficulty due to the high-dimensional nature of gene expression data. We propose
      a multivariate batch adjustment method that effectively eliminates inter-gene
      batch effects. The proposed method utilizes high-dimensional sparse covariance
      estimation based on a factor model and a hard thresholding. Another important
      aspect of the proposed method is that if it is known that one of the batches is
      produced in a superior condition, the other batches can be adjusted so that they
      resemble the target batch. We study high-dimensional asymptotic properties of the
      proposed estimator and compare the performance of the proposed method with some
      popular existing methods with simulated data and gene expression data sets.

PMID- 24687562
TI  - Evaluation of time, attendance of medical staff and resources for radiotherapy in
      pediatric and adolescent patients. The DEGRO-QUIRO trial.
AB  - BACKGROUND: The German Society of Radiation Oncology (DEGRO) initiated a
      multicenter trial to develop and evaluate adequate modules to assert core
      procedures in radiotherapy. The aim of this prospective evaluation was to
      methodical assess the required resources for radiotherapy in pediatric and
      adolescent patients. MATERIAL AND METHODS: At three radiotherapy centers of
      excellence (University Hospitals of Heidelberg and Munster, the Medical School of
      Hannover), the manpower and time required for radiotherapy in pediatric and
      adolescent patients was prospectively documented consistently over a 2-year
      period. The data were collected using specifically developed standard forms and
      were evaluated using specific process analysis tools. RESULTS: A total number of
      1914 data sets were documented and carefully analyzed. The personnel time
      requirements for all occupational groups were calculated as total time needed for
      a specific procedure and mean time per person. Regarding radiotherapy in general
      anesthesia, the required manpower was higher. The personnel time requirements in
      these cases were also longer, mainly due to longer room occupancy. Overall, the
      required resources were remarkably similar between the three different
      departments and may, therefore, be considered as representative. CONCLUSION: For
      the first time, the personnel time requirements of a radiotherapy department for
      the maintenance, protection, and optimization of operational readiness for
      radiotherapy in pediatric and adolescent patients with and without general
      anesthesia were determined methodically.

PMID- 24687563
TI  - Stability of spinal bone metastases in breast cancer after radiotherapy: a
      retrospective analysis of 157 cases.
AB  - PURPOSE: This retrospective analysis was performed to evaluate osteolytic bone
      lesions of breast cancer in the thoracic and lumbar spine after radiotherapy (RT)
      in terms of stability using a validated scoring system. METHODS: The stability of
      157 osteolytic metastases, treated from January 2000 to January 2012, in 115
      patients with breast cancer was evaluated retrospectively using the Taneichi
      score. Predictive factors for stability were analyzed and survival rates were
      calculated. RESULTS: Eighty-five (54%) lesions were classified as unstable prior
      to RT. After 3 and 6 months, 109 (70%) and 124 (79%) lesions, respectively, were
      classified as stable. Thirty fractures were detected prior to RT, and after RT
      seven cases (4.5%) with pathologic fractures were found within 6 months. None of
      the examined predictive factors showed significant correlation with stability 6
      months after RT. After a median follow-up of 16.7 months, Kaplan-Meier estimates
      revealed an overall survival of 83% after 5 years. CONCLUSION: The majority of
      patients showed an improved or unchanged stability of the involved vertebral
      bodies after 6 months. The patients showed only minor cancer-related morbidity
      during follow-up and reached comparably high survival rates.

PMID- 24687564
TI  - Yeasts associated with plums and their potential for controlling brown rot after
      harvest.
AB  - Bacterial and yeast antagonists isolated from fruit surfaces have been effective
      in controlling various post-harvest diseases, and several microbial antagonists
      have been developed into commercial products. Our knowledge of the fruit
      microbial community, with the exception of grapes, apples and some citrus fruit,
      is rudimentary and the potential of the resident yeasts for biocontrol remains
      largely unknown. We determined the occurrence of yeasts on plum surfaces during
      fruit development from the pre-hardening stage until harvest for 2 years. A total
      of 16 species from 13 genera were isolated. Species from three genera,
      basidiomycetes Rhodotorula (29.5%) and Sporidiobolus (24.7%) and the dimorphic
      ascomycete genus Aureobasidium (24.7%), constituted 78.7% of all isolations and
      were recovered throughout fruit development, while Cryptococcus spp. constituted
      only 6.2% of the total plum isolates. The yeast community in the final sampling
      was significantly different from the first three samplings, reflecting a rapidly
      changing fruit habitat during the maturation of fruit. For example,
      Hanseniaspora, Pichia, Zygosaccharomyces and Wickerhamomyces occurred only on the
      most mature fruit. Screening of the yeasts for antagonistic activity against
      Monilinia fructicola, a fungus that causes brown rot, revealed a range of
      biocontrol activities. Several isolates provided complete control of the decay on
      plums, challenged with a pathogen suspension of 10(3) conidia/ml and > 90% of
      control on fruit inoculated with the pathogen at a concentration 10 times higher.
      Some of the best antagonists included A. pullulans and R. phylloplana.
      Populations of both of these antagonists increased rapidly by several orders of
      magnitude in wounds of plums incubated at 24oC and 4oC. Our results indicate that
      plum surfaces harbour several yeast species, with excellent potential for use in
      biological control of brown rot of stone fruits.

PMID- 24687565
TI  - Molecular response of the axillary lymph node microenvironment to metastatic
      colonization.
AB  - Breast stroma plays an active role in tumorigenesis, undergoing both phenotypic
      and molecular changes that facilitate and promote tumor development and growth.
      The metastatic microenvironment also plays a role in successful colonization;
      however, genetic changes in these secondary microenvironments are not well
      described. To improve understanding of molecular changes associated with
      metastatic colonization, gene expression patterns from lymph node tissues from
      women with at least one positive, as well as one negative node, were compared.
      Lymph node tissue was microdissected and hybridized to U133A 2.0 gene expression
      arrays. Differential expression was detected using Partek((r)) Genomics SuiteTM
      6.6 with FDR <0.05 and >2-fold change defining significance. Twenty-two genes
      were differentially expressed, 14 genes, including AZGP1, FOXA1 and PIP, were
      expressed at significantly higher levels in colonized lymph nodes and eight
      genes, such as CXCL2 and HPGDS, were expressed at significantly higher levels in
      non-metastatic lymph nodes. Thus, lymph node tissues harboring metastases have
      different gene expression patterns from those without metastases. Many
      differentially expressed genes are involved in cellular proliferation and
      survival, immune function and mesenchymal-epithelial transition, suggesting that
      repression of immune response and restoration of an epithelial phenotype in the
      host tissue are critical for successful establishment of lymph node metastases.

PMID- 24687567
TI  - Five people are arrested in Spain's first case of attempted organ trafficking.

PMID- 24687566
TI  - Using Rasch analysis to examine the distress thermometer's cut-off scores among a
      mixed group of patients with cancer.
AB  - PURPOSE: The distress thermometer (DT) is commonly used in cancer care to improve
      detection of distress. The DT's recommended cut-off score of 4 or 5 has typically
      been established using the Hospital Anxiety and Depression Scale (HADS) by
      receiver operating characteristic curve analysis. The present analysis
      complements these studies by critically examining the use of the HADS to identify
      the DT's cut-off score and corroborating the DT's cut-off scores using item
      response theory (Rasch analysis). METHODS: The DT and HADS were completed by 340
      patients with cancer. Rasch dimensionality analysis was performed on the HADS
      Total, and test characteristic curves were examined to equate the DT and the HADS
      subscales. Identified DT cut-off scores were then examined for their sensitivity
      and specificity. RESULTS: Rasch analysis did not support the unidimensionality of
      HADS-Total. The test characteristic curves indicated that a cut-off score of >=8
      on the HADS-Anxiety and HADS-Depression subscales was equivalent to a score of 6
      and 7 on the DT, respectively. However, a DT cut-off score of 5 resulted in the
      best balance between sensitivity and specificity across the HADS-Anxiety and HADS
      Depression subscales. CONCLUSIONS: Despite being a popular practice, the present
      findings did not support combining the HADS-Anxiety and HADS-Depression subscales
      to identify the DT's cut-off score. Furthermore, these results inform the use of
      the DT as a preliminary screening tool and suggest that when a single screen is
      used, a DT cut-off score of 6 or 7 might be more appropriate than the typical cut
      off score of 4.

PMID- 24687568
TI  - Mechanical thrombectomy in acute ischemic stroke-experience from 6 years of
      practice.
AB  - INTRODUCTION: We present our results from the first 6 years with mechanical
      thrombectomy in the treatment of ischemic stroke. METHODS: Every patient treated
      with mechanical thrombectomy for acute ischemic stroke from September 2005 to
      December 2011 was consecutively included in this retrospective analysis. Baseline
      and outcome data were retrieved from computerized records at the hospital.
      National Institute of Health Stroke Scale (NIHSS) score and the modified Rankin
      Scale (mRS) score were used as outcome parameters. Favorable outcome was defined
      as a mRS score of 0-2, corresponding to independence in activities of daily
      living. We also evaluated revascularization and severe adverse events, with focus
      on symptomatic intracranial hemorrhage. RESULTS: Good functional outcome (mRS 0
      2) was achieved in 50 % (120/240) of all patients. For patients with no
      neurological deficit prior to stroke onset (i.e., mRS = 0 before stroke), the
      proportion with good functional outcome was 54 %. Symptomatic hemorrhages
      occurred in 4.6 % of the cases (5.7 % in the anterior circulation). CONCLUSION:
      In summary, our results supports that mechanical thrombectomy is a safe and
      effective method to restore blood flow in selected patients suffering from an
      acute ischemic stroke.

PMID- 24687570
TI  - [Mild therapeutic hypothermia in cardiac arrest].

PMID- 24687571
TI  - [Mild therapeutic hypothermia in cardiac arrest].

PMID- 24687572
TI  - Screening for abnormal placentation and adverse pregnancy outcomes with maternal
      serum biomarkers in the second trimester.
AB  - Second trimester biomarkers were initially introduced with the intent of
      screening for neural tube defects and then subsequently for Down syndrome. It was
      soon realized that these markers can be indirect evidence of abnormal
      placentation and, therefore, can be used for screening for adverse pregnancy
      outcomes. Several new biomarkers have subsequently been described with
      conflicting findings regarding their efficiency for screening for adverse
      pregnancy outcomes. Although a biologically feasible mechanism has been proposed
      for the role of these biomarkers, they still fall short of an ideal screening
      test to be clinically useful.

PMID- 24687573
TI  - In vivo measurement of the pressure signal in the intervertebral disc of an
      anesthetized sheep.
AB  - The purpose of the present study was to measure the intradiscal pressure signal
      of an anesthetized sheep under spontaneous breathing. An ultra-miniature fiber
      optic high-pressure sensor was implanted into the nucleus pulposus of the fifth
      lumbar intervertebral using a dorsolateral transforaminal approach. Results
      suggested the periodicity of the intradiscal pressure signal was similar to the
      mean respiratory rate of the animal. The average resting intradiscal pressure was
      also calculated and compared to available data.

PMID- 24687574
TI  - Comparison of two commercial ELISAs against an in-house ELISA for measuring
      soluble CD26 in human serum.
AB  - BACKGROUND: CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV
      (DPPIV) activity in its extracellular region. The relevance of sCD26 levels and
      disease activity has been reported in rheumatic or infectious disease. For
      certain metabolic and endocrine conditions, DPPIV inhibitors were recently
      developed as a new class of antidiabetic drugs that act by inhibiting DPPIV, the
      enzyme that inactivates incretin hormone. Higher levels of sCD26 in diabetic
      patients have been shown to be associated with a poor clinical response to DPPIV
      inhibitors, with sCD26/DPPIV being an adipokine that may impair insulin
      sensitivity. With the increasing use of serum sCD26 and DPPIV enzyme activity as
      biomarkers with potential clinical implications, accurate measurements of serum
      sCD26 levels and DPPIV enzyme activity are needed. METHODS: We compare two
      commercially widely available and an in-house enzyme-linked immunosorbent assays
      (ELISAs) for measurement of serum sCD26 in healthy or diabetic human sera.
      RESULTS: The significant discrepancies among the results obtained from
      commercially available and the in-house sCD26 assays were found. We also observed
      that a linear correlation between serum sCD26 level and DPPIV enzyme activity
      exists with the in-house ELISA, while the commercial ELISAs demonstrate a lack of
      consistency between serum sCD26 level and DPPIV enzyme activity. CONCLUSION:
      These data strongly suggest that new commercial assays for sCD26 plasma levels
      need detailed evaluation and validation with samples from clinically well
      characterized patients, and results obtained from these newer assays should be
      compared to those obtained from well-established in-house assays such as our
      assay or other validated sCD26 ELISA assays.

PMID- 24687575
TI  - Regulation of high mobility group box 1 and hypoxia in the migration of
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have been increasingly offered for tissue
      regeneration with the premise that they can survive and thrive amidst the
      microenvironment of injured or degenerate tissues. The role of high mobility
      group box 1 (HMGB1) and hypoxia in the proliferation and migration of rat bone
      marrow MSCs (rBM-MSCs) has been investigated. First, the effect of HMGB1 on the
      proliferation of rBM-MSCs was determined. Second, to evaluate the regulation of
      hypoxia and HMGB1 in the migration of rBM-MSCs, cells in the wound healing model
      were exposed to four conditions: normoxia (20% O2) and complete medium, normoxia
      and HMGB1, hypoxia (1% O2) and complete medium, hypoxia and HMGB1. RT-PCR and
      Western blotting were used to measure the expression of migration-related genes
      and proteins. HMGB1 inhibited the proliferation of rBM-MSCs; HMGB1 alone or
      together with hypoxia and promoted the migration of MSCs and upregulated the
      expression of HIF-1alpha and SDF-1. These results demonstrated that HMGB1
      arrested the proliferation of rBM-MSCs, but enhanced the migration of rBM-MSCs
      which could be further improved by hypoxia. This study strengthens current
      understanding of the interaction between MSCs and the microenvironment of damaged
      tissues.

PMID- 24687576
TI  - Effect of pre-warmed intravenous fluids on perioperative hypothermia and
      shivering after ambulatory surgery under monitored anesthesia care.
AB  - PURPOSE: The aim of this study was to evaluate the effects of pre-warmed
      (approximately 41  degrees C) intravenous fluids (IV) on perioperative
      hypothermia and postoperative shivering in female patients undergoing short,
      ambulatory urological surgery under monitored anesthesia care (MAC). METHODS:
      Patients between the ages of 35 and 80 years were randomly assigned to either the
      pre-warmed (n = 27) or the room temperature (n = 26) group. According to group
      allocation, either pre-warmed IV fluids that had been stored in a warming cabinet
      for at least 8 h or room temperature IV fluids were administered intraoperatively
      up to approximately 600-700 ml, including a bolus infusion of 10 ml/kg within 20
      min. Perioperative core temperatures at the tympanic membrane, postoperative
      shivering, subjective thermal comfort, and the use of forced-air warming
      interventions in the post-anesthesia care unit (PACU) were recorded. RESULTS:
      Mean core temperatures were significantly higher in the pre-warmed group than
      they were in the room temperature group after 10 ml/kg preload fluid was
      administered, at the end of the operation, and on admission to the PACU (p =
      0.004, p = 0.02, and p = 0.008, respectively). The incidence of hypothermia (<36 
      degrees C) was significantly lower in the pre-warmed group (n = 4) than in the
      room temperature group (n = 11, p = 0.035) upon PACU admission. The postoperative
      shivering incidence was also significantly lower in the pre-warmed group (n = 2)
      than in the room temperature group (n = 8, p = 0.039). CONCLUSIONS: Infusion of
      pre-warmed IV fluid improved the postoperative recovery profile by decreasing
      hypothermia and shivering in female patients undergoing short, ambulatory
      urological surgery under MAC.

PMID- 24687577
TI  - Selective detection of carbohydrates and their peptide conjugates by ESI-MS using
      synthetic quaternary ammonium salt derivatives of phenylboronic acids.
AB  - We present new tags based on the derivatives of phenylboronic acid and apply them
      for the selective detection of sugars and peptide-sugar conjugates in mass
      spectrometry. We investigated the binding of phenylboronic acid and its
      quaternary ammonium salt (QAS) derivatives to carbohydrates and peptide-derived
      Amadori products by HR-MS and MS/MS experiments. The formation of complexes
      between sugar or sugar-peptide conjugates and synthetic tags was confirmed on the
      basis of the unique isotopic distribution resulting from the presence of boron
      atom. Moreover, incorporation of a quaternary ammonium salt dramatically improved
      the efficiency of ionization in mass spectrometry. It was found that the
      formation of a complex with phenylboronic acid stabilizes the sugar moiety in
      glycated peptides, resulting in simplification of the fragmentation pattern of
      peptide-derived Amadori products. The obtained results suggest that
      derivatization of phenylboronic acid as QAS is a promising method for sensitive
      ESI-MS detection of carbohydrates and their conjugates formed by non-enzymatic
      glycation or glycosylation. 

PMID- 24687580
TI  - Pre-exposure to adenosine, acting via A(2A) receptors on endothelial cells,
      alters the protein kinase A dependence of adenosine-induced dilation in skeletal
      muscle resistance arterioles.
AB  - Adenosine (ADO) is an endogenous vasodilatory purine widely recognized to be a
      significant contributor to functional hyperaemia. Despite this, many aspects of
      the mechanisms by which ADO induces dilation in small resistance arterioles are
      not established, or appear contradictory. These include: identification of the
      primary receptor subtype; its location on endothelial (EC) or vascular smooth
      muscle cells; whether ADO acts on KATP channels in these resistance vessels; and
      the contribution of cAMP/protein kinase A (PKA) signalling to the response. In
      intravital microscopy studies of intact or EC-denuded skeletal muscle arterioles,
      we show that ADO acts via A2A receptors located on ECs to produce vasodilation
      via activation of KATP channels located on vascular smooth muscle cells.
      Importantly, we found that the signalling pathway involves cAMP as expected, but
      that a requirement for PKA activation is demonstrable only if the vessel is not
      pre-exposed to ADO. That is, PKA-dependent signalling varies with pre-exposure to
      ADO. Further, we show that PKA activation alone is not sufficient to dilate these
      arterioles; an additional EC calcium-dependent signalling mechanism is required
      for vasodilation to ADO. The ability of arterioles in situ to respond to
      occupancy of a specific receptor by utilizing different cell signalling pathways
      under different conditions to produce the same response allows the arteriole to
      respond to key homeostatic requirements using more than a single signalling
      mechanism. Clearly, this is likely to be physiologically advantageous, but the
      role for this signalling flexibility in the integrated arteriolar response that
      underlies functional hyperaemia will require further exploration.

PMID- 24687581
TI  - CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by
      altering the contractile protein expression.
AB  - Abundant data indicate that pathogenesis in allergic airways disease is
      orchestrated by an aberrant T-helper 2 (Th2) inflammatory response. CD4(+) T
      cells have been localized to airway smooth muscle (ASM) in both human asthmatics
      and in rodent models of allergic airways disease, where they have been implicated
      in proliferative responses of ASM. Whether CD4(+) T cells also alter ASM
      contractility has not been addressed. We established an in vitro system to assess
      the ability of antigen-stimulated CD4(+) T cells to modify contractile responses
      of the Brown Norway rat trachealis muscle. Our data demonstrated that the
      unloaded velocity of shortening (Vmax) of ASM was significantly increased upon 24
      h co-incubation with antigen-stimulated CD4(+) T cells, while stress did not
      change. Enhanced Vmax was dependent upon contact between the CD4(+) T cells and
      the ASM and correlated with increased levels of the fast (+)insert smooth muscle
      myosin heavy chain isoform. The levels of myosin light chain kinase and myosin
      light chain phosphorylation were also increased within the muscle. The
      alterations in mechanics and in the levels of contractile proteins were
      transient, both declining to control levels after 48 h of co-incubation. More
      permanent alterations in muscle phenotype might be attainable when several
      inflammatory cells and mediators interact together or after repeated antigenic
      challenges. Further studies will await new tissue culture methodologies that
      preserve the muscle properties over longer periods of time. In conclusion, our
      data suggest that inflammatory cells promote ASM hypercontractility in airway
      hyper-responsiveness and asthma.

PMID- 24687582
TI  - Fibre type-specific satellite cell response to aerobic training in sedentary
      adults.
AB  - In the present study, we sought to determine the effect of a traditional, 12 week
      aerobic training protocol on skeletal muscle fibre type distribution and
      satellite cell content in sedentary subjects. Muscle biopsies were obtained from
      the vastus lateralis [n = 23 subjects (six male and 17 female); body mass index
      30.7 +/- 1.2 kg m(-2)] before and after 12 weeks of aerobic training performed on
      a cycle ergometer. Immunohistochemical analyses were used to quantify myosin
      heavy chain (MyHC) isoform expression, cross-sectional area and satellite cell
      and myonuclear content. Following training, a decrease in MyHC hybrid type
      IIa/IIx fibre frequency occurred, with a concomitant increase in pure MyHC type
      IIa fibres. Pretraining fibre type correlated with body mass index, and the
      change in fibre type following training was associated with improvements in
      maximal oxygen consumption. Twelve weeks of aerobic training also induced
      increases in mean cross-sectional area in both MyHC type I and type IIa fibres.
      Satellite cell content was also increased following training, specifically in
      MyHC type I fibres, with no change in the number of satellite cells associated
      with MyHC type II fibres. With the increased satellite cell content following
      training, an increase in myonuclear number per fibre also occurred in MyHC type I
      fibres. Hypertrophy of MyHC type II fibres occurred without detectable myonuclear
      addition, suggesting that the mechanisms underlying growth in fast and slow
      fibres differ. These data provide intriguing evidence for a fibre type-specific
      role of satellite cells in muscle adaptation following aerobic training.

PMID- 24687584
TI  - Smooth muscle BK channel activity influences blood pressure independent of
      vascular tone in mice.
AB  - The large conductance voltage- and Ca(2+)-activated K(+) (BK) channel is an
      important determinant of vascular tone and contributes to blood pressure
      regulation. Both activities depend on the ancillary BKbeta1 subunit. To determine
      the significance of smooth muscle BK channel activity for blood pressure
      regulation, we investigated the potential link between changes in arterial tone
      and altered blood pressure in BKbeta1 knockout (BKbeta1(-/-)) mice from three
      different genetically defined strains. While vascular tone was consistently
      increased in all BKbeta1(-/-) mice independent of genetic background, BKbeta1(-/
      ) strains exhibited increased (strain A), unaltered (strain B) or decreased
      (strain C) mean arterial blood pressures compared to their corresponding
      BKbeta1(+/+) controls. In agreement with previous data on aldosterone regulation
      by renal/adrenal BK channel function, BKbeta1(-/-) strain A mice have increased
      plasma aldosterone and increased blood pressure. Consistently, blockade of
      mineralocorticoid receptors by spironolactone treatment reversibly restored the
      elevated blood pressure to the BKbeta1(+/+) strain A level. In contrast, loss of
      BKbeta1 did not affect plasma aldosterone in strain C mice. Smooth muscle
      restricted restoration of BKbeta1 expression increased blood pressure in BKbeta1(
      /-) strain C mice, implying that impaired smooth muscle BK channel activity
      lowers blood pressure in these animals. We conclude that BK channel activity
      directly affects vascular tone but influences blood pressure independent of this
      effect via different pathways.

PMID- 24687583
TI  - Polycystins and partners: proposed role in mechanosensitivity.
AB  - Mutations of the two polycystins, PC1 and PC2, lead to polycystic kidney disease.
      Polycystins are able to form complexes with numerous families of proteins that
      have been suggested to participate in mechanical sensing. The proposed role of
      polycystins and their partners in the kidney primary cilium is to sense urine
      flow. A role for polycystins in mechanosensing has also been shown in other cell
      types such as vascular smooth muscle cells and cardiac myocytes. At the plasma
      membrane, polycystins interact with diverse ion channels of the TRP family and
      with stretch-activated channels (Piezos, TREKs). The actin cytoskeleton and its
      interacting proteins, such as filamin A, have been shown to be essential for
      these interactions. Numerous proteins involved in cell-cell and cell
      extracellular matrix junctions interact with PC1 and/or PC2. These multimeric
      protein complexes are important for cell structure integrity, the transmission of
      force, as well as for mechanosensing and mechanotransduction. A group of
      polycystin partners are also involved in subcellular trafficking mechanisms.
      Finally, PC1 and especially PC2 interact with elements of the endoplasmic
      reticulum and are essential components of calcium homeostasis. In conclusion, we
      propose that both PC1 and PC2 act as conductors to tune the overall cellular
      mechanosensitivity.

PMID- 24687585
TI  - Adiponectin is sufficient, but not required, for exercise-induced increases in
      the expression of skeletal muscle mitochondrial enzymes.
AB  - Adiponectin (Ad) has been proposed to be a regulator of mitochondrial biogenesis
      in skeletal muscle, and necessary for exercise-induced increases in mitochondrial
      content. We first confirmed that Ad could acutely increase the expression of
      mitochondrial proteins during a 10 h incubation in isolated soleus and extensor
      digitorum longus (EDL) muscles. Next, we further examined the role of Ad as a
      regulator of mitochondrial content using Ad knockout (AdKO) mice. The AdKO
      animals showed no differences in resting VO2, respiratory exchange ratio, or in
      time to exhaustion during exercise when compared to wild-type (WT) mice. There
      was a reduction in resting palmitate oxidation in isolated soleus from AdKO
      animals (-23%, P < 0.05) but not EDL, and 5-aminoimidazole-4-carboxamide (AICAR)
      stimulated palmitate oxidation was similar in both genotypes regardless of
      muscle. There were no differences in protein markers of mitochondrial content
      (COX4, CORE1, CS, PDHE1alpha) in red and white gastrocnemius between WT and AdKO
      animals. A single bout of treadmill running increased the phosphorylation of AMP
      activated protein kinase (AMPK) and the mRNA expression of mitochondrial proteins
      in red and white gastrocnemius in both WT and AdKO animals, with no differences
      between genotypes. Finally, 8 weeks of chronic exercise training increased the
      protein content of mitochondrial markers similarly (~25-35%) in red gastrocnemius
      from both WT and AdKO mice. Collectively, our results demonstrate that the
      absence of Ad is not accompanied by reductions in mitochondrial protein content,
      or a reduction in aerobic exercise capacity. We conclude that Ad is not required
      for the maintenance of mitochondrial content, or for exercise-induced increases
      in skeletal muscle mitochondrial proteins.

PMID- 24687587
TI  - Convergent validity of the Integrated Visual and Auditory Continuous Performance
      Test (IVA+Plus): associations with working memory, processing speed, and
      behavioral ratings.
AB  - Though the Integrated Visual and Auditory Continuous Performance Test (IVA +
      Plus) is commonly used by researchers and clinicians, few investigations have
      assessed its convergent and discriminant validity, especially with regard to its
      use with children. The present study details correlates of the IVA + Plus using
      measures of cognitive ability and ratings of child behavior (parent and teacher),
      drawing upon a sample of 90 psychoeducational evaluations. Scores from the IVA +
      Plus correlated significantly with the Working Memory and Processing Speed
      Indexes from the Fourth Edition of the Wechsler Intelligence Scales for Children
      (WISC-IV), though fewer and weaker significant correlations were seen with
      behavior ratings scales, and significant associations also occurred with WISC-IV
      Verbal Comprehension and Perceptual Reasoning. The overall pattern of relations
      is supportive of the validity of the IVA + Plus; however, general cognitive
      ability was associated with better performance on most of the primary scores of
      the IVA + Plus, suggesting that interpretation should take intelligence into
      account. 

PMID- 24687586
TI  - Adenosine receptor inhibition attenuates the suppression of postexercise
      cutaneous blood flow.
AB  - The time-dependent contributions of active vasodilation (e.g. nitric oxide) and
      noradrenergic vasoconstriction to the postexercise suppression of cutaneous
      perfusion despite persistent hyperthermia remain unknown. Moreover, adenosine
      receptors have been shown to mediate the decrease in cutaneous perfusion
      following passive heating. We examined the time-dependent modulation of nitric
      oxide synthase, noradrenergic vasoconstriction and adenosine receptors on
      postexercise cutaneous perfusion. Eight males performed 15 min of high-intensity
      (85% VO2 max) cycling followed by 60 min of recovery in temperate ambient
      conditions (25 degrees C). Four microdialysis probes were inserted into the
      forearm skin and continuously infused with: (1) lactated Ringer solution
      (Control); (2) 10 mm N(G)-nitro-l-arginine methyl ester (l-NAME; nitric oxide
      synthase inhibitor); (3) 10 mm bretylium tosylate (BT; inhibitor of noradrenergic
      vasoconstriction); or (4) 4 mm theophylline (THEO; adenosine receptor inhibitor).
      Cutaneous vascular conductance (CVC) was expressed as a percentage of maximum and
      was calculated as perfusion units (laser Doppler) divided by mean arterial
      pressure. End-exercise CVC was similar in Control, THEO and BT (P > 0.1), but CVC
      with l-NAME (39 +/- 4%) was lower than Control (59 +/- 4%, P < 0.01). At 20 min
      of recovery, Control CVC (22 +/- 3%) returned to baseline levels (19 +/- 2%, P =
      0.11). Relative to Control, CVC was reduced by l-NAME for the first 10 min of
      recovery whereas CVC was increased with BT for the first 30 min of recovery (P <
      0.03). In contrast, CVC with THEO was elevated throughout the 60 min recovery
      period (P <= 0.01) compared to Control. We show that adenosine receptors appear
      to have a major role in postexercise cutaneous perfusion whereas nitric oxide
      synthase and noradrenergic vasoconstriction are involved only earlier during
      recovery.

PMID- 24687589
TI  - Constrained-geometry bisphosphazides derived from 1,8-diazidonaphthalene:
      synthesis, spectroscopic characteristics, structural features, and theoretical
      investigations.
AB  - Investigations on the Staudinger reaction between 1,8-diazidonaphthalene and
      phosphorous(III) building blocks, a key step in the synthesis of superbasic
      bisphosphazene proton sponges, yielded a set of bisphosphazides with a
      constrained geometry 1,8-disubstituted naphthalene backbone. This compound class
      has attracted our interest not only due to their surprisingly high stability, but
      in particular because of their theoretically predicted basicity in the range of
      their bisphosphazene analogues that can be referred to the constrained geometry
      interaction of two highly basic nitrogen atoms. Eleven new bisphosphazides
      bearing simple P-amino groups as well as P-guanidino substituents,
      azaphosphatrane moieties, P2 building blocks, or chiral P-amino substituents
      derived from L-proline are presented. They were studied concerning their
      spectroscopic properties and partly also their chromophoric and structural
      features. In the case of the pyrrolidino-substituted TPPN(2N2) (TPPN = 1,8
      bis(trispyrrolidinophosphazenyl)naphthalene), the stepwise nitrogen elimination
      is investigated theoretically and experimentally, which led to the isolation and
      structural characterization of TPPN(1N2) bearing a phosphazide and a phosphazene
      functionality in one molecule. Attempts to protonate the obtained bisphosphazides
      and to prove the computationally predicted pKBH(+) values through NMR titration
      reactions resulted in their decay, which again was rationalized by theoretical
      calculations. Altogether we present the so far most extensive spectroscopic,
      structural and theoretical investigation of constrained geometry bisphosphazides
      and their Bronsted and Lewis basic properties.

PMID- 24687588
TI  - Analysis of verbal fluency ability in Alzheimer's disease: the role of
      clustering, switching and semantic proximities.
AB  - The underlying nature of verbal fluency deficits in Alzheimer's disease (AD) was
      investigated in this study. Participants were 48 individuals with AD and 48
      cognitively healthy older adults. Fluency performance on letter and category
      tasks was analyzed across two 30-s intervals for total words produced, mean
      cluster size, and total switches. Compared with the control group, AD
      participants produced fewer words and switches on both fluency tasks and had a
      reduced category cluster size. The AD group was differentially impaired on
      category compared with letter fluency and produced more repetitive responses but
      fewer category exemplars than controls on the category task. A multidimensional
      scaling approach revealed that AD participants' semantic maps were similar to
      controls. Overall, the data suggest that executive abilities involving search and
      retrieval processes and a reduced availability of semantically related words
      contributed to the AD group's poorer performance despite similar temporal recall
      and organizational patterns. 

PMID- 24687590
TI  - Sperm-specific AKAP3 is a dual-specificity anchoring protein that interacts with
      both protein kinase a regulatory subunits via conserved N-terminal amphipathic
      peptides.
AB  - cAMP-dependent protein kinase A (PKA) plays important regulatory roles during
      mouse spermatogenesis. PKA-mediated signaling has been shown to regulate gene
      expression, chromatin condensation, capacitation, and motility during sperm
      development and behavior, although how PKA is regulated in spatiotemporal manners
      during spermatogenesis is not fully understood. In the present study, we found
      that PKA subunit isoforms are expressed and localized differently in meiotic and
      post-meiotic mouse spermatogenic cells. Regulatory subunit I alpha (RIalpha) is
      expressed in spermatocytes and round spermatids, where it is localized diffusely
      throughout the cytoplasm of cells. During late spermiogenesis, RIalpha abundance
      gradually decreases. On the other hand, RIIalpha is expressed constantly
      throughout meiotic and post-meiotic stages, and is associated with cytoskeletal
      structures. Among several A kinase anchoring proteins (AKAPs) expressed in the
      testis, sperm-specific AKAP3 can be found in the cytoplasm of elongating
      spermatids and interacts with RIalpha, as demonstrated by both in vivo and in
      vitro experiments. In mature sperm, AKAP3 is exclusively found in the principal
      piece of the flagellum, coincident with only RIIalpha. Mutagenesis experiments
      further showed that the preferential interactions of AKAP3 with PKA regulatory
      subunits are mediated by two highly conserved amphipathic peptides located in the
      N-terminal region of AKAP3. Thus, AKAP3 is a dual-specificity molecule that
      modulates PKA isotypes in a spatiotemporal manner during mouse spermatogenesis.

PMID- 24687591
TI  - Microenvironment influences vascular differentiation of murine cardiovascular
      progenitor cells.
AB  - We examined the effects of the microenvironment on vascular differentiation of
      murine cardiovascular progenitor cells (CPCs). We isolated CPCs and seeded them
      in culture exposed to the various extracellular matrix (ECM) proteins in both two
      dimensional (2D) and 3D culture systems. To better understand the contribution of
      the microenvironment to vascular differentiation, we analyzed endothelial and
      smooth muscle cell differentiation at both day 7 and day 14. We found that
      laminin and vitronectin enhanced vascular endothelial cell differentiation while
      fibronectin enhanced vascular smooth muscle cell differentiation. We also
      observed that the effects of the 3D electrospun scaffolds were delayed and not
      noticeable until the later time point (day 14), which may be due to the amount of
      time necessary for the cells to migrate to the interior of the scaffold. The
      study characterized the contributions of both ECM proteins and the addition of a
      3D culture system to continued vascular differentiation. Additionally, we
      demonstrated the capability bioengineer a CPC-derived vascular graft.

PMID- 24687592
TI  - Headache attack followed by rapid disease progression in pediatric moyamoya
      disease--how should we manage it?
AB  - CASE REPORT: A 4-year-old female was presented at our hospital with frequent
      right frontal headache attack. She was diagnosed with moyamoya disease and was
      conservatively followed up. One year later, the frequency of headache gradually
      decreased. However, follow-up MR imaging revealed that the disease stage markedly
      progressed in the right side and cerebral infarction occurred in the temporal
      lobe with atrophy of the right frontal lobe. She underwent direct and indirect
      revascularization on the right side. CONCLUSION: Aware of this case, we would
      like to emphasize that headache may be one subtype of ischemic attacks and
      require frequent MR follow-up to see the disease course. If there is any sign of
      disease progression, immediate surgical intervention should be indicated to avoid
      irreversible brain damage.

PMID- 24687593
TI  - Effect of a Bluetooth-implemented hearing aid on speech recognition performance:
      subjective and objective measurement.
AB  - OBJECTIVES: The object was to evaluate speech perception improvement through
      Bluetooth-implemented hearing aids in hearing-impaired adults. METHODS: Thirty
      subjects with bilateral symmetric moderate sensorineural hearing loss
      participated in this study. A Bluetooth-implemented hearing aid was fitted
      unilaterally in all study subjects. Objective speech recognition score and
      subjective satisfaction were measured with a Bluetooth-implemented hearing aid to
      replace the acoustic connection from either a cellular phone or a loudspeaker
      system. In each system, participants were assigned to 4 conditions: wireless
      speech signal transmission into hearing aid (wireless mode) in quiet or noisy
      environment and conventional speech signal transmission using external microphone
      of hearing aid (conventional mode) in quiet or noisy environment. Also,
      participants completed questionnaires to investigate subjective satisfaction.
      RESULTS: Both cellular phone and loudspeaker system situation, participants
      showed improvements in sentence and word recognition scores with wireless mode
      compared to conventional mode in both quiet and noise conditions (P < .001).
      Participants also reported subjective improvements, including better sound
      quality, less noise interference, and better accuracy naturalness, when using the
      wireless mode (P < .001). CONCLUSIONS: Bluetooth-implemented hearing aids helped
      to improve subjective and objective speech recognition performances in quiet and
      noisy environments during the use of electronic audio devices.

PMID- 24687594
TI  - Induction chemotherapy followed by concurrent chemoradiotherapy for advanced
      stage oropharyngeal squamous cell carcinoma with HPV and P16 testing.
AB  - OBJECTIVE: The objective was to report our experience with advanced stage
      oropharyngeal squamous cell carcinoma treated sequentially with induction
      chemotherapy followed by concurrent chemoradiotherapy. METHODS: Retrospective
      chart review identified 49 eligible patients with advanced stage oropharyngeal
      squamous cell carcinoma treated with induction chemotherapy followed by
      concurrent chemoradiotherapy. HPV and p16(INK4A) testing was performed on
      pathology specimens. Follow-up of over 11 months was required unless a death or
      treatment failure occurred before that time. RESULTS: Treatment with induction
      chemotherapy followed by concurrent chemoradiotherapy resulted in 44/48 (90%)
      complete durable response. One death occurred from pulmonary embolism. Toxicity
      profiles were comparable to other published data. Average follow-up was 3.9
      years. Oncologic failure rates among subgroups showed 5.7% failure for HPV+/p16+
      cancer, 9.1% failure for HPV-/p16+ cancer, 100% failure for HPV-/p16- cancer, 0%
      failure for nonsmokers, and 17.9% failure for smokers. CONCLUSIONS: This study
      showed favorable outcomes in terms of durable oncologic response and acceptable
      toxicity profiles. It is notable that 36/49 patients were HPV+/p16+ and 11/49
      were HPV-/p16+. Only 2 patients were HPV-/p16-, and both died as a result of
      oncologic failures. This highlights the importance of obtaining HPV and p16
      testing in studies evaluating the efficacy of treatments for oropharyngeal
      squamous cell carcinoma.

PMID- 24687595
TI  - [Perioperative steroid dosing in steroid treated patients undergoing colorectal
      surgery].

PMID- 24687596
TI  - Treatment of upper cervical spine instability with posterior fusion plus
      atlantoaxial pedicle screw.
AB  - Clinical results of posterior fusion plus pedicle screw fixation in the treatment
      of upper cervical spine instability were taken under consideration. 24 patients
      with atlantoaxial instability were treated with C1-2 pedicle screws and rods
      fixation under general anesthesia. There were 18 males and 6 females with mean
      age of 49.8 years (age range 17-69 years). The postoperative radiographs verified
      good position of all screws, with satisfactory atlantoaxial reduction. Follow-up
      for 3-45 months (average 23 months) showed no spinal cord and vertebral artery
      injury or interfixation failure. Atlantoaxial alignment and stability were
      restored without complication due to instrumentation. In conclusion, posterior
      atlantoaxial pedicle screw and rod fixation provide immediate three-dimensional
      rigid fixation of atlantoaxial joint and are more effective techniques compared
      with previously reported techniques.

PMID- 24687597
TI  - Aortic pulse wave velocity is associated with measures of subclinical target
      organ damage in patients with mild hypertension.
AB  - We evaluated the temporal association between aortic arterial stiffness and
      subclinical target organ damage, including renal function decline, left
      ventricular geometric remodeling, and left ventricular diastolic dysfunction in
      patients with mild hypertension. Automatic pulse wave velocity (PWV) measuring
      system was applied to examine carotid-femoral PWV (CFPWV) reflecting aortic
      arterial stiffness in 644 essential hypertensive patients. Clinical data were
      collected, and cardiac structure and function were assessed by echocardiography.
      CFPWV was significantly and positively associated with left ventricular mass
      index (r = 0.153, P = 0.018), relative wall thickness (r = 0.235, P < 0.001), and
      left atrial diameter (r = 0.192, P = 0.003), and negatively with E/A ratio (r = 
      0.361, P < 0.001) and creatinine clearance (r = -0.248, P < 0.001). Logistic
      regression analysis demonstrated that CFPWV remained significantly correlated
      with renal function decline (P = 0.011), left ventricular diastolic dysfunction
      (P = 0.009) and left ventricular geometric remodeling (P = 0.020). Higher CFPWV
      was independently associated with greater burden of subclinical disease in renal
      impairment, left ventricular geometric remodeling and diastolic dysfunction.

PMID- 24687598
TI  - Packaging, amplification, and appraisal of the recombinant tumor-selective type I
      herpes simplex virus carrying GALV.fus gene.
AB  - The aim of the study was to successfully construct three plasmids, which include
      the GALV.fus gene plasmid regulated by the herpes simplex virus type 1 (HSV-1)
      late expression gene-UL38 promoter and induced by HSV-1 (HSV-UL38P-GALV.fus), the
      cytomegalovirus promoter without tumor specificity (CMVP) GALV.fus plasmid (HSV
      CMVP-GALV.fus), and the control plasmid in which the GALV.fus gene fragment was
      replaced by the enhanced green fluorescent protein (EGFP) gene fragment (HSV-CMVP
      EGFP). The three constructed plasmids were all packaged and named as Synco-2,
      Synco-1, and Baco-1. The plasmids were amplified in coliform bacterium and
      transfected into Vero cells using lipofectamine. These recombinant HSV-1 were
      amplified in Vero cells and purified by conventional methods of cesium chloride,
      TCID50 method is used to measure virus titers. The total RNA was then extracted
      from the HepG2 cells transfected by Synco-1 and Synco-2, and the expression of
      GALV.fus mRNA was detected by RT-PCR. The three recombinant HSV-1 vectors were
      propagated in Vero cells and purified by cesium chloride density gradient
      centrifugation, titrated by TCID50 method, and packaged. The titers of Baco-1,
      Synco-1, and Synco-2 were 3 * 10(10), 1 * 10(11), and 4 * 10(10) pfu/ml. The
      GALV.fus gene was identified in the infected HepG2 cells by RT-PCR method.

PMID- 24687599
TI  - Oxygen deficit alleviates phosphate overaccumulation toxicity in OsPHR2
      overexpression plants.
AB  - Overexpression of OsPHR2 increases phosphate (Pi) uptake and causes
      overaccumulation of Pi in rice plants, which is toxic to rice plants when they
      are grown in media with a sufficient Pi supply. The toxicity that results from
      OsPHR2 overexpression can be significantly relieved by growing the plants in a
      waterlogged paddy field. A comparison of the Pi uptake and growth status of
      OsPHR2-overexpression plants (PHR2-Oe plants) grown in paddy fields or in a
      laboratory setting in aerated or stagnant hydroponic conditions indicated that
      the oxygen limitation that is present in paddy fields and in stagnant rice
      culture solutions inhibits the Pi overaccumulation toxicity of PHR2-Oe plants by
      reducing their Pi uptake. Quantitative RT-PCR demonstrated that the expression of
      Pi-starvation-induced (PSI) genes was induced by oxygen limitation in both wild
      type and PHR2-Oe plants. The induction of PSI genes is the consequence of
      reducing the Pi concentration in stagnant plants. Thus, when evaluating the
      efficiency of Pi use in rice germplasm or transgenic materials under hydroponic
      conditions, the impact of the low oxygen condition that exists in waterlogged
      paddies should be considered. 

PMID- 24687600
TI  - Kidney injuries related to ipilimumab.
AB  - Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T
      lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic
      melanoma and other cancers and have shown promising results. Inhibition of CTLA-4
      characteristically induces well-known side effects called "immune-related adverse
      events" (irAEs). IrAEs mainly include colitis, dermatitis, hepatitis,
      endocrinopathies; uveitis, iridocyclitis, neuropathies, and inflammatory myopathy
      have occasionally been reported. Kidney involvement is rare. We report 2 cases of
      acute granulomatous interstitial nephritis and present, based on literature
      review, renal disorders related to Ipilimumab therapy. Autoimmune symptoms have
      to be carefully checked for patients treated with CTLA-4 inhibitors. In order to
      reduce the risk of sequelae, early recognition of irAEs and treatment initiation
      are crucial. 

PMID- 24687601
TI  - Discrepancy in placental echogenicity: a sign of twin anemia polycythemia
      sequence.
AB  - Twin anemia polycythemia sequence (TAPS) is a form of twin-to-twin transfusion
      syndrome that occurs very rarely and may not be diagnosed until after delivery.
      The condition leads to increased risk of perinatal morbidity and mortality. We
      present two cases of monochorionic diamniotic twins, in which the diagnosis of
      TAPS was made after documenting a discrepancy in the echodensities of the two
      portions of the placenta. Postnatal hemoglobin differences between the twins
      confirmed the diagnosis of TAPS. On the basis of these two cases, it appears that
      the heterogeneity in placental echogenicity is a sign of TAPS and Doppler
      measurement of middle cerebral artery peak systolic velocity is helpful for early
      diagnosis and management with timely delivery.

PMID- 24687602
TI  - Joint geriatric and old-age psychiatric wards in the U.K., 1940s-early 1990s: a
      historical study.
AB  - OBJECTIVE: This study aims to investigate the history of joint geriatric
      psychiatric units. For policy making and planning of high-quality clinical
      service models, clinical and social contexts need to be considered. Longitudinal,
      contextual information can be provided by historical analyses, including the
      successes and failures of earlier, similar services. Historical analyses
      complement clinical, randomised controlled studies and may contribute to ensuring
      optimum outcomes for future schemes. METHODS: Standard historical methodology was
      used, including searching published sources and institutional and personal
      archives and conducting a 'witness seminar' and individual oral history
      interviews. RESULTS: Proposals to create joint units have existed since 1947.
      Most clinically successful units were led by enthusiastic, dedicated clinicians.
      Joint units had the potential to provide appropriate assessment and treatment for
      patients with multiple disorders and education for staff and students. Joint
      units never became widespread. CONCLUSIONS: Reasons for the limited success of
      joint geriatric-psychiatric units might have included personalities of
      individuals, administrative boundaries separating geriatrics and medicine,
      unequal numbers of geriatricians and old-age psychiatrists, varying professional
      ideologies about the meaning of 'integrated' services, lack of reciprocity for
      each other's inpatients and lack of government support. Identified stumbling
      blocks need to be considered when planning joint clinical schemes. If current
      research indicates benefits of integrated wards for patients and their families,
      there needs to be ways to ensure that personal factors and fashions of management
      or government re-prioritisation will not lead to their premature termination.

PMID- 24687603
TI  - Investigation of composition of neobladder [corrected] stone taken from
      Sanliurfa, Southern of Turkey.

PMID- 24687605
TI  - Spatio-temporal dynamics of arbuscular mycorrhizal fungi associated with glomalin
      related soil protein and soil enzymes in different managed semiarid steppes.
AB  - Temporal and spatial patterns of arbuscular mycorrhizal fungi (AMF) and glomalin
      and soil enzyme activities were investigated in different managed semiarid
      steppes located in Inner Mongolia, North China. Soils were sampled in a depth up
      to 30 cm from non-grazed, overgrazed, and naturally restored steppes from June to
      September. Roots of Leymus chinense (Trin.) Tzvel. and Stipagrandis P. Smirn.
      were also collected over the same period. Results showed that overgrazing
      significantly decreased the total mycorrhizal colonization of S. grandis; total
      colonization of L. chinensis roots was not significantly different in the three
      managed steppes. Nineteen AMF species belonging to six genera were isolated.
      Funneliformis and Glomus were dominant genera in all three steppes. Spore density
      and species richness were mainly influenced by an interaction between plant
      growth stage and management system (P < 0.001). Spore densities were higher in 0
      10-cm soil depth. AMF species richness was significantly positively correlated
      with soil acid phosphatase activity, alkaline phosphatase activity, and two
      Bradford-reactive soil protein (BRSP) fractions (P < 0.01). It is concluded that
      the dynamics of AMF have highly temporal and spatial patterns that are related to
      soil glomalin and phosphatase activity in different managed semiarid steppes.
      Based on these observations, AMF communities could be useful indicators for
      evaluating soil quality and function of semiarid grassland ecosystems. 

PMID- 24687604
TI  - Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to
      sorafenib treatment.
AB  - Death rates from hepatocellular carcinoma (HCC) are steadily increasing, yet
      therapeutic options for advanced HCC are limited. We identify a subset of mouse
      and human HCCs harboring VEGFA genomic amplification, displaying distinct
      biologic characteristics. Unlike common tumor amplifications, this one seems to
      work via heterotypic paracrine interactions; stromal VEGF receptors (VEGFR),
      responding to tumor VEGF-A, produce hepatocyte growth factor (HGF) that
      reciprocally affects tumor cells. VEGF-A inhibition results in HGF downregulation
      and reduced proliferation, specifically in amplicon-positive mouse HCCs.
      Sorafenib-the first-line drug in advanced HCC-targets multiple kinases, including
      VEGFRs, but has only an overall mild beneficial effect. We found that VEGFA
      amplification specifies mouse and human HCCs that are distinctly sensitive to
      sorafenib. FISH analysis of a retrospective patient cohort showed markedly
      improved survival of sorafenib-treated patients with VEGFA-amplified HCCs,
      suggesting that VEGFA amplification is a potential biomarker for HCC response to
      VEGF-A-blocking drugs. SIGNIFICANCE: Using a mouse model of inflammation-driven
      cancer, we identified a subclass of HCC carrying VEGFA amplification, which is
      particularly sensitive to VEGF-A inhibition. We found that a similar
      amplification in human HCC identifies patients who favorably responded to
      sorafenib-the first-line treatment of advanced HCC-which has an overall moderate
      therapeutic efficacy.

PMID- 24687608
TI  - Relevance of human parechovirus detection in cerebrospinal fluid samples from
      young infants with sepsis-like illness.
AB  - BACKGROUND: The human parechoviruses (HPeVs) were recently recognized as
      important viral pathogens involved in various illnesses in young children.
      However, routine detection is not performed in most clinical laboratories.
      Therefore, in this study, we aim to assess the relevance of HPeV detection in
      cerebrospinal fluid (CSF) of infants, according to clinical presentation.
      METHODS: A total of 120 CSF specimens collected during 2012 from infants aged
      less than 1 year and previously reported negative for Herpes simplex virus (HSV)
      and enterovirus were selected. HPeV detection was performed with a commercially
      available real-time RT-PCR and HPeV strains from positive samples were
      subsequently genotyped by sequencing. RESULTS: HPeV RNA was detected in nine
      (7.5%) CSF samples. The median age of infected children was 41 days (range: 19
      122 days). HPeV genotyping could be performed on five samples and three HPeV-3,
      one HPeV-1, and one HPeV-4 were identified. Hyperthermia associated with mottled
      skin was the predominant clinical presentation. Most clinical presentations of
      HPeV-infected infants were mild with a final diagnosis of sepsis-like illness.
      The median hospital stay was 3.5 days and five children received antibiotics.
      CONCLUSION: Routine detection of HPeV in CSF may allow differential diagnosis of
      enterovirus infection and improve etiologic identification of sepsis-like illness
      in children.

PMID- 24687606
TI  - Arbuscular mycorrhizal fungal community divergence within a common host plant in
      two different soils in a subarctic Aeolian sand area.
AB  - There is rising awareness that different arbuscular mycorrhizal (AM) fungi have
      different autoecology and occupy different soil niches and that the benefits they
      provide to the host plant are dependent on plant-AM fungus combination. However,
      the role and community composition of AM fungi in succession are not well known
      and the northern latitudes remain poorly investigated ecosystems. We studied AM
      fungal communities in the roots of the grass Deschampsia flexuosa in two
      different, closely located, successional stages in a northern Aeolian sand area.
      The AM fungal taxa richness in planta was estimated by cloning and sequencing
      small subunit ribosomal RNA genes. AM colonization, shoot delta (13)C signature,
      and %N and %C were measured. Soil microbial community structure and AM fungal
      mycelium abundance were estimated using phospholipid (PLFA) and neutral lipid
      (NLFA) analyses. The two successional stages were characterized by distinct
      plant, microbial, and fungal communities. AM fungal species richness was very low
      in both the early and late successional stages. AM frequency in D. flexuosa roots
      was higher in the early successional stage than in the late one. The AM fungal
      taxa retrieved belonged to the genera generally adapted to Arctic or extreme
      environments. AM fungi seemed to be important in the early stage of the
      succession, suggesting that AM fungi may help plants to better cope with the
      harsh environmental conditions, especially in an early successional stage with
      more extreme environmental fluctuations. 

PMID- 24687609
TI  - [Adolescents and young adults with cancer--analogies and differences to young
      adults with congenital heart defects].

PMID- 24687610
TI  - Drug handling in a paediatric intensive care unit--can errors be prevented by a
      three-step intervention?
AB  - BACKGROUND: Drug handling in paediatric intensive care units (PICU) is prone to
      medication errors. We aimed to identify type and prevalence of those errors and
      to assess preventative interventions. METHODS: Prospective intervention study
      investigating a 3-step intervention for preventing errors in drug handling in a
      10-bed PICU of a university hospital. Nurses' drug handling was monitored in
      daily routine to identify the number of patients affected by errors and overall
      prevalence and types of errors in drug handling. We implemented a comprehensive
      intervention consisting of an information handout, a training course, and a 76
      page reference book tailored to reduce the prevalence. RESULTS: The prevalence of
      errors in drug handling decreased from 83 % (555 errors/668 processes)to 63 %
      (554/883; p < 0.001) after the intervention. The number of affected patients
      remained unchanged (95 % vs. 89 %, p = 0.370).Peroral (PO) drugs (1.33
      errors/process) were more error-prone than intravenous (IV) drugs(0.64), despite
      being used less frequently (27 % vs.73 % of all processes, p < 0.001). The
      interventions decreased the prevalence to 0.77 errors/process(p < 0.001) in PO
      and to 0.52 in IV drugs (p = 0.025). CONCLUSION: Errors in drug handling were
      alarmingly frequent. PO drugs were frequently subject to errors, even though
      being used less frequently. The implementation of a comprehensive intervention
      succeeded in reducing the prevalence of errors. Yet further refinements are
      necessary to decrease also the number of affected patients.

PMID- 24687611
TI  - Musculoskeletal pain: a new algorithm for differential diagnosis of a cardinal
      symptom in pediatrics.
AB  - Musculoskeletal pain (MSP) is a common childhood complaint associated with
      multiple differential diagnoses, including cancer. Considering the expanding
      spectrum of diagnostics, evaluat-ing a young patient with MSP is a challenge
      today, particularly for non-specialists in a primary care setting. Since
      childhood cancer is rare and most cardinal symptoms mimic rather non-serious
      diseases, misdiagnosis is not uncommon, but of significant prognostic relevance.
      To build the appropriate bridge between primary and secon-dary care for a child
      presenting with MSP, thereby preventing treatment delay and longterm sequelae,
      initial evaluation should follow a comprehensive, multidisciplinary, systematic
      and stepwise approach, which unites the patient's individual anamnestic,
      psychosocial, and clinical charac-teristics. After a systematic review of the
      literature, we generated multidisciplinarily quality-assured recommendations for
      efficient, rational and cost-effective primary care assessment of pediatric MSP.
      The algorithm promotes the identification and structured interpretation of the
      patient's individual clinical clues. It should serve the primary care physician
      to recognize when further intervention, rather than reassurance and follow-up, is
      needed using the minimum amount of testing to make an appropriate, prompt
      diagnosis in the clinical situation "child presenting with MSP". A German version
      of this algorithm has been published in the Guideline-Portal of The Association
      of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen
      Medizinischen Fachgesellschaften", AWMF) in November 2013.

PMID- 24687612
TI  - Sufficient dimension reduction on the mean and rate functions of recurrent
      events.
AB  - The counting process with a Cox-type intensity function has been extensively
      applied to analyze recurrent event data, which assume that the underlying
      counting process is a time-transformed Poisson process and that the covariates
      have multiplicative or additive effects on the mean and rate functions of the
      counting process. The existing statistical inference, however, often encounters
      difficulties due to high-dimensional covariates, such as in gene expression and
      single nucleotide polymorphism data that have revolutionized our understanding of
      cancer recurrence and other diseases. In this paper, a technique of sufficient
      dimension reduction is applied to the mean and rate function for the number of
      occurrences of events over time. A two-step procedure is proposed to estimate the
      model components: first, a nonparametric estimator is proposed for the baseline,
      and then the basis of the central subspace and its dimension are estimated
      through a modified slicing inverse regression. On the basis of the estimated
      structural dimension and on the basis of the central subspace, we can estimate
      the regression function by using the local linear regression. A simulation is
      performed to confirm and assess the theoretical findings, and an application is
      demonstrated on a set of chronic granulomatous disease data.

PMID- 24687613
TI  - Studies on primary uveal and cutaneous melanoma cell interaction with
      vitronectin.
AB  - We have examined the diversity between primary uveal (92-1 and Mel202) and
      cutaneous (FM55P and IGR-39) melanoma cells in their interaction with
      vitronectin, and established the effect of integrins and beta1,6-branched N
      oligosaccharides on this process. The adhesion level of uveal melanoma cells to
      vitronectin was at least twice lower than that of cutaneous ones, but all cells
      tested repaired scratch wounds on vitronectin-coated surfaces with similar speed.
      Swainsonine treatment, by reducing the amount of beta1,6-branches, significantly
      decreased cell attachment in all cases, but reduction of wound healing efficiency
      was compromised only in cutaneous melanoma cell. Functional blocking antibodies
      used in adhesion and migration assays revealed that integrin alphavbeta3 was
      strongly involved in adhesion and migration only in cutaneous melanoma cells, but
      its role here was less pronounced than that of integrin alphavbeta5. However, in
      uveal melanoma the specific anti-alphavbeta5 integrin antibody had no impact on
      migration speed. Therefore, the anti-alpha3beta1 integrin antibody was used in
      order to explain the nature of uveal melanoma interaction with vitronectin, which
      caused a mild decrease in adhesion efficiency and reduced their motility.
      Expression of alphavbeta5 integrin differed between the cell lines, but there was
      no distinct pattern to distinguish uveal melanoma from cutaneous melanoma. In
      conclusion, alphavbeta5, but not alphavbeta3 integrin is heavily involved in
      uveal melanoma cell interaction with vitronectin. The role of beta1,6-branched N
      glycans in the adhesion, but not during migration, of all cells to vitronectin
      has been confirmed. 

PMID- 24687614
TI  - Coregistered autofluorescence-optical coherence tomography imaging of human lung
      sections.
AB  - Autofluorescence (AF) imaging can provide valuable information about the
      structural and metabolic state of tissue that can be useful for elucidating
      physiological and pathological processes. Optical coherence tomography (OCT)
      provides high resolution detailed information about tissue morphology. We present
      coregistered AF-OCT imaging of human lung sections. Adjacent hematoxylin and
      eosin stained histological sections are used to identify tissue structures
      observed in the OCT images. Segmentation of these structures in the OCT images
      allowed determination of relative AF intensities of human lung components. Since
      the AF imaging was performed on tissue sections perpendicular to the airway axis,
      the results show the AF signal originating from the airway wall components free
      from the effects of scattering and absorption by overlying layers as is the case
      during endoscopic imaging. Cartilage and dense connective tissue (DCT) are found
      to be the dominant fluorescing components with the average cartilage AF intensity
      about four times greater than that of DCT. The epithelium, lamina propria, and
      loose connective tissue near basement membrane generate an order of magnitude
      smaller AF signal than the cartilage fluorescence.

PMID- 24687615
TI  - The 2014 Surgeon General's report: "The health consequences of smoking--50 years
      of progress": a paradigm shift in cancer care.

PMID- 24687616
TI  - Construction and characterisation of near-isogenic Plutella xylostella
      (Lepidoptera: Plutellidae) strains resistant to Cry1Ac toxin.
AB  - BACKGROUND: Resistance to insecticidal Bacillus thuringiensis (Bt) toxins has
      arisen in multiple populations of the worldwide Brassica pest Plutella xylostella
      (L.). To help elucidate the mechanism of resistance to Bt Cry1Ac toxin in a
      population from Florida, two pairs of near-isogenic lines (NILs) were developed.
      RESULTS: NILs were generated using either backcross or recombinant inbred line
      methodologies and evaluated for near-isogenicity with inter-simple-sequence
      repeat (ISSR) markers. Backcross line BC6F4 maintained a similar level of Cry1Ac
      resistance to parental strain DBM1Ac-R (>5000-fold) yet showed 98.24% genetic
      similarity to the susceptible parental strain DBM1Ac-S. Single-pair backcrosses
      between DBM1Ac-S and BC6F4 revealed that Cry1Ac resistance was controlled by one
      recessive autosomal locus. BC6F4 exhibited high levels of cross-resistance to
      Cry1Ab and Cry1Ah but not to Cry1Ca or Cry1Ie. CONCLUSION: Near-isogenic strains
      were constructed to provide a reliable biological system to investigate the
      mechanism of Cry1Ac resistance in P. xylostella. These data suggest that
      resistance to Cry1Ac, Cry1Ab and Cry1Ah is probably caused by the alteration of a
      common receptor not recognised by Cry1Ca or Cry1Ie. Understanding Bt toxin cross
      resistance provides valuable information to consider when developing pest control
      strategies to delay resistance evolution. (c) 2014 Society of Chemical Industry.

PMID- 24687617
TI  - Drug-eluting stents in patients with anterior STEMI undergoing primary
      angioplasty: a substudy of the DESERT cooperation.
AB  - BACKGROUND: Several concerns have emerged on the higher risk of in-stent
      thrombosis after drug-eluting stent (DES) implantation, especially in the setting
      of STEMI patients. Few data have even been reported in high-risk patients, such
      as those with anterior MI. Therefore this represents the aim of the current
      study. METHODS: The literature was scanned by formal searches of electronic
      databases (MEDLINE and CENTRAL). We examined all completed randomized trials of
      DES for STEMI. The following key words were used for study selection: randomized
      trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES,
      sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. No
      language restrictions were enforced. RESULTS: Individual patient's data were
      obtained from 11 out of 13 trials, including a total of 2,782 patients with
      anterior MI [1,739 or 62.5% randomized to DES and 1,043 or 37.5% randomized to
      bare-metal stent (BMS)]. At long-term follow-up, no significant benefit was
      observed with DES as compared to BMS in terms of mortality [9.8 vs 10.9%, HR (95%
      CI) = 0.81 (0.61, 1.07), p = 0.13, p heterogeneity = 0.18], reinfarction [8.8 vs
      6.4%, respectively; HR (95% CI) = 1.14 (0.80, 1.61), p = 0.47, p heterogeneity =
      0.82], and stent thrombosis [5.6 vs 5%, OR (95% CI) = 0.88 (0.59, 1.30), p =
      0.51, p heterogeneity = 0.65], whereas DES was associated with a significant
      reduction in terms of target-vessel revascularization (TVR) [13.7 vs 23.4%; OR
      (95% CI) = 0.56 (0.46, 0.69), p < 0.0001, p het = 0.81] that was observed at both
      early (within 1 year) [7 vs 14.7%, HR (95% CI) = 0.56 (0.46, 0.69), p < 0.0001, p
      het = 0.81] and late (>1 year) follow-up [7.2 vs 9%, HR (95% CI) = 0.67 (0.47,
      0.96), p = 0.03, p het = 0.96]. CONCLUSIONS: This study showed that among
      patients with anterior STEMI undergoing primary angioplasty, SES and PES, as
      compared to BMS, are associated with a significant reduction in TVR at long-term
      follow-up. No concerns were found with the use of first-generation DES in terms
      of mortality.

PMID- 24687618
TI  - Left atrial appendage closure in a patient with atrial fibrillation after
      mechanical mitral valve replacement and cardio-embolic stroke despite effective
      oral anticoagulant therapy: a case report.

PMID- 24687619
TI  - Cardiac fusion and complex congenital cardiac defects in thoracopagus twins:
      diagnostic value of cardiac CT.
AB  - Most thoracopagus twins present with cardiac fusion and associated congenital
      cardiac defects, and assessment of this anatomy is of critical importance in
      determining patient care and outcome. Cardiac CT with electrocardiographic
      triggering provides an accurate and quick morphological assessment of both
      intracardiac and extracardiac structures in newborns, making it the best imaging
      modality to assess thoracopagus twins during the neonatal period. In this case
      report, we highlight the diagnostic value of cardiac CT in thoracopagus twins
      with an interatrial channel and complex congenital cardiac defects. 

PMID- 24687620
TI  - Imaging of spinal injury in abusive head trauma: a retrospective study.
AB  - BACKGROUND: Spinal imaging has been a neglected part of abusive head trauma (AHT)
      imaging. As most of the radiographs and CT spine are negative in AHT in infants,
      the cervical spine is assumed to be normal. There is increasing evidence in the
      role of injury to brainstem and cervical cord in the pathogenesis of AHT. In
      addition, in courts of law, there is fierce debate about AHT, its mimics and
      other disparate nontraumatic diagnoses explaining the neuroradiological and
      skeletal findings. However, this discussion ignores the evidence and significance
      of spinal injury. We sought to study the cervical spine in an AHT cohort to
      understand the true prevalence of spinal injuries in AHT and contrast it with
      cohorts of accidental and nontraumatic groups to give the clinicians a robust
      diagnostic tool in evaluating AHT. OBJECTIVE: The purpose of this study is to
      compare the relative incidence of spinal ligamentous and soft-tissue
      abnormalities on spinal MRI among three groups of children ages <48 months: 1)
      those with AHT, 2) those with accidental trauma, and 3) those with nontraumatic
      conditions. MATERIALS AND METHODS: This comparative study included 183 children
      who underwent spine MRI: 67 with AHT, 46 with accidental trauma and a clinical
      suspicion of spinal injury, and 70 with nontraumatic conditions. Clinical and
      radiographic findings were collected in all cases and were analyzed
      retrospectively to identify MRI evidence of traumatic spinal injuries. The
      incidence of spinal injuries among the three groups was compared. The incidence
      of spinal ligamentous injuries was calculated for those with and without
      radiographic evidence of hypoxic-ischemic encephalopathy. All comparisons were
      performed using Fisher exact test with P < 0.05 considered statistically
      significant. RESULTS: Cervical spine ligamentous injuries (predominantly the
      nuchal, atlanto-occipital and atlanto-axial ligaments) were present in 78% of the
      AHT group, 46% of the accidental trauma group and 1% of the nontraumatic group;
      all of these differences were statistically significant. Among the AHT group,
      ligamentous injuries were statistically correlated with evidence of brain
      ischemia. CONCLUSION: Injury to the cervical spinal posterior ligamentous complex
      is common in AHT and even more prevalent than in clinically symptomatic traumatic
      cases. The high correlation between the radiographic findings of occipitocervical
      ligamentous injuries and hypoxic-ischemic brain injury is consistent with an
      interpretation that transient upper occipitocervical spinal cord injury in AHT
      leads to disordered breathing and results in hypoxic-ischemic encephalopathy. We
      recommend imaging the entire spine in AHT to properly identify and classify these
      injuries.

PMID- 24687621
TI  - Ischial apophyseal fracture in an abused infant.
AB  - We report a previously healthy 4-month-old who presented to the hospital with leg
      pain and swelling and no history of trauma. Radiographs demonstrated a comminuted
      left femur fracture. Given the concern for child abuse, skeletal survey was
      performed and revealed four vertebral compression deformities. Although abuse was
      suspected, the possibility of a lytic lesion associated with the femur fracture
      and multiple spinal abnormalities raised the possibility of an underlying process
      such as Langerhans cell histiocytosis. Subsequently 18F-NaF positron emission
      tomographic (PET) scintigraphy revealed increased tracer activity in the ischium,
      and MRI confirmed an ischial apophyseal fracture. Pelvic fractures, particularly
      ischial fractures, are extremely rare in the setting of child abuse. This case
      report describes the multimodality imaging findings of an ischial fracture in an
      abused infant. 

PMID- 24687622
TI  - Age at death and linear enamel hypoplasias: testing the effects of childhood
      stress and adult socioeconomic circumstances in premature mortality.
AB  - OBJECTIVE: The aim of this study was to test the association between linear
      enamel hypolasias and adult socioeconomic circumstances with age at death in a
      modern skeletal sample of known age. Specifically, this study wishes to test
      whether there is a relationship between early life stressors, environmental
      quality in adult life and premature mortality. METHODS: The presence/absence of
      LEH and the number of LEH episodes were recorded in 113 adult males from the
      Lisbon identified skeletal collection. The association between LEH and age was
      quantified using linear regression and binary logistic regression models,
      calculating crude and adjusted linear regression coefficients and odds ratios.
      The models were adjusted for year of birth, socioeconomic and migration status,
      and cause of death. RESULTS: The presence and number of LEH were related to
      premature mortality. Individuals expressing at least one enamel defect survived
      9.0 years less or were 2.5 times more likely to die before 53 years of age
      compared to individuals with no LEH. However, when controlling for the
      confounding factors considered, the association between LEH and age became
      nonsignificant. CONCLUSIONS: The results indicate that although early life
      stressors, identified as LEH, seem strongly associated with premature mortality,
      adulthood socioeconomic circumstances accounts for most of the decreased
      longevity. This suggests that either macroscopically identified LEH in the
      permanent canine do not measure stressors early in life, or that a cumulative
      adversity model is a more adequate explanation.

PMID- 24687623
TI  - Transient ablation of alveolar macrophages leads to massive pathology of
      influenza infection without affecting cellular adaptive immunity.
AB  - Alveolar macrophages (AMs), localized at the pulmonary air-tissue interface, are
      one of the first lines of defense that interact with inhaled airborne pathogens
      such as influenza viruses. By using a new CD169-DTR transgenic mouse strain we
      demonstrate that specific and highly controlled in vivo ablation of this myeloid
      cell subset leads to severe impairment of the innate, but not adaptive, immune
      responses and critically affects the progression of the disease. In fact, AM
      ablated mice, infected with a normally sublethal dose of PR8 influenza virus,
      showed dramatically increased virus load in the lungs, severe airway
      inflammation, pulmonary edema and vascular leakage, which caused the death of the
      infected animals. Our data highlight the possibilities for new therapeutic
      strategies focusing on modulation of AMs, which may efficiently boost innate
      responses to influenza infections. 

PMID- 24687624
TI  - Cerebrovascular and ischemic heart disease in young adults born preterm: a
      population-based Swedish cohort study.
AB  - Preterm birth is associated with overall cardiovascular mortality in young
      adulthood, but which specific conditions that underlie this association is
      unknown. We studied mortality and morbidity from cerebrovascular and ischemic
      heart disease in individuals born preterm. In a nationwide Swedish study, we
      included 1,306,943 individuals without congenital malformations born between 1983
      and 1995, followed from 15 years of age to December 31st, 2010. Of these, 73,489
      (5.6 %) were born preterm (<37 weeks of gestation). Cox proportional hazards
      regression analysis was used to calculate hazard ratios (HR) with 95 % confidence
      intervals (CI), after adjusting for maternal characteristics and birth weight for
      gestational age. Of 955 incident cases of cerebrovascular disease, 58 (6.1 %)
      occurred in preterm born subjects. The corresponding numbers of ischemic heart
      disease cases were 180 and 13 (7.2 %), respectively. Birth before 32 weeks was
      associated with a nearly twofold increased risk of cerebrovascular disease;
      adjusted HR, (95 % CI) = 1.89 (1.01-3.54) compared to term born individuals,
      whereas individuals born at 32-36 weeks were not at increased risk. Preterm birth
      was not associated with later ischemic heart disease; no cases of ischemic heart
      disease were recorded among those born before 32 weeks and the HR (95 % CI) for
      those born at 32-36 weeks of gestation was 1.45 (0.81-2.57), compared to term
      born individuals. Birth before 32 weeks is associated with increased risk of
      cerebrovascular disease in young adulthood. Our data suggest that cardiovascular
      health promotion in follow-up programs after very preterm birth may be
      beneficial.

PMID- 24687625
TI  - Eradications as scientific experiments: progress in simultaneous eradications of
      two major invasive taxa from a Mediterranean island.
AB  - BACKGROUND: Black rats, Rattus rattus, and mat-forming iceplants, Carpobrotus
      aff. acinaciformis and Carpobrotus edulis, are pervasive pests on Mediterranean
      islands. Their cumulative impacts on native biotas alter the functioning of
      island ecosystems and threaten biodiversity. A report is given here of the first
      attempt to eradicate both taxa from a protected nature reserve in south-eastern
      France (Bagaud Island). In order to minimise unwanted hazardous outcomes and
      produce scientific knowledge, the operations were embedded in a four-step
      strategy including initial site assessment, planning, restoration and monitoring.
      RESULTS: Trapping, which resulted in the removal of 1923 rats in 21 045 trap
      nights, made it possible to eliminate a substantial proportion of the resident
      rat population and to reduce the amount of rodenticide delivered in the second
      stage of the operation. Forty tons of Carpobrotus spp. were manually uprooted
      from a total area of 18 000 m(2) ; yet careful monitoring over a decade is still
      required to prevent germinations from the seed bank. CONCLUSION: Two years after
      the beginning of the interventions, both eradication operations are still
      ongoing. Biosecurity measures have been implemented to reduce reinvasion risks of
      both taxa. With the long-term monitoring of various native plants and animals,
      Bagaud Island will become a reference study site for scientific purposes.

PMID- 24687626
TI  - Calculation of corrected body height in idiopathic scoliosis: comparison of four
      methods.
AB  - PURPOSE: The aim of the study was to analyze four radiographic methods of
      calculating the loss of body height associated with scoliosis. METHODS: Thirty
      patients with right thoracic idiopathic scoliosis were examined with standing
      postero-anterior radiographs. Cobb angles of the upper thoracic, main thoracic
      and lumbar curves were measured. The loss of body height due to scoliosis was
      measured directly on the radiographs and then calculated using the methods of
      Bjure, Kono, Stokes and Ylikoski, respectively. The reproducibility of
      calculations was tested. Detailed analysis of two patients with similar Cobb
      angle but different trunk height was performed. RESULTS: The mean Cobb angle of
      the main thoracic curve was 46 degrees  (21 degrees -74 degrees ). The mean loss
      of body height was 23 mm (11-43 mm) calculated by method of Bjure, 7 mm (-24 to
      46 mm) by Kono, 20 mm (5-47 mm) by Stokes, 14 mm (3-36 mm) by Ylikoski, versus 18
      mm (3-50 mm) measured directly on radiographs. The overall difference between the
      loss of body heights was significant (p < 0.0001), with significant differences
      in pairs for: Bjure versus Kono (p < 0.0001), Stokes versus Kono (p = 0.0002),
      Kono versus measured (p = 0.0061) and Bjure versus Ylikoski (p = 0.0386). Strong
      linear correlation between the methods was found (r >= 0.92; p < 0.0001). High
      reproducibility of height loss calculations was noticed. The two patients with
      similar Cobb angle and different trunk height revealed similar height loss
      calculated, while different loss measured on radiographs. CONCLUSIONS: There
      existed no overall agreement between the four methods of calculation of the loss
      of body height associated with scoliosis. Calculations based on the Cobb angle
      produced inaccuracy and could be supplemented with data considering trunk size.

PMID- 24687628
TI  - Enzymatic control of chitosan gelation for delivery of periodontal ligament
      cells.
AB  - The aim of this study is to optimize enzymatic control over gelation of chitosan
      based hydrogels for the delivery of periodontal ligament cells (PDLCs). The
      results reveal that the gelation time, strength, and degradation rate of the
      chitosan hydrogels can be controlled precisely by variation of the urea and
      urease concentrations. PDLCs remain viable inside these hydrogels for up to 30
      days. Cells released from the hydrogel upon degradation and collected after 3,
      15, and 30 days are able to form colonies and osteogenically differentiate. In
      conclusion, the enzymatic control over the gelation of chitosan hydrogels offers
      options for the delivery of PDLCs. 

PMID- 24687629
TI  - Determined persistence: achieving and sustaining job satisfaction among nurse
      practitioners.
AB  - PURPOSE: Job satisfaction of nurse practitioners (NPs) has been studied using
      quantitative methods. A grounded theory approach was used in this study to
      understand the contextual nature of the NPs' description of job satisfaction from
      a personal perspective. DATA SOURCE: A grounded theory approach as described by
      Glaser and Strauss was used in this study. The study took place in a rural
      northeastern state. The researcher conducted face-to-face interviews using open
      ended questions with 15 participants. Constant comparative method was utilized to
      analyze data culminating in a basic social process. CONCLUSIONS: The participants
      described holistic care as the foundation of their work and their relationship
      with patients as determining factors of job satisfaction. When NPs felt as though
      patient care was compromised, they became dissatisfied. NPs were highly satisfied
      when providing holistic care and within an environment that respected their
      professional values. IMPLICATIONS FOR PRACTICE: In order to maintain
      accessibility to high-quality health care, it is imperative to understand the
      factors that contribute to job satisfaction of NPs. As the healthcare system
      evolves, healthcare policymakers and healthcare organizations must develop
      strategies to ensure job satisfaction among NPs.

PMID- 24687627
TI  - The pathobiology of diabetic vascular complications--cardiovascular and kidney
      disease.
AB  - With the increasing incidence of obesity and type 2 diabetes, it is predicted
      that more than half of Americans will have diabetes or pre-diabetes by 2020.
      Diabetic patients develop vascular complications at a much faster rate in
      comparison to non-diabetic individuals, and cardiovascular risk is increased up
      to tenfold. With the increasing incidence of diabetes across the world, the
      development of vascular complications will become an increasing medical burden.
      Diabetic vascular complications affect the micro- and macro-vasculature leading
      to kidney disease often requiring dialysis and transplantation or cardiovascular
      disease increasing the risk for myocardial infarction, stroke and amputations as
      well as leading to premature mortality. It has been suggested that many complex
      pathways contribute to the pathobiology of diabetic complications including
      hyperglycaemia itself, the production of advanced glycation end products (AGEs)
      and interaction with the receptors for AGEs such as the receptor for advanced
      glycation end products (RAGE), as well as the activation of vasoactive systems
      such as the renin-angiotensin aldosterone system (RAAS) and the endothelin
      system. More recently, it has been hypothesised that reactive oxygen species
      derived from NAD(P)H oxidases (Nox) may represent a common downstream mediator of
      vascular injury in diabetes. Current standard treatment of care includes the
      optimization of blood glucose and blood pressure usually including inhibitors of
      the renin-angiotensin system. Although these interventions are able to delay
      progression, they fail to prevent the development of complications. Thus, there
      is an urgent medical need to identify novel targets in diabetic vascular
      complications which may include the blockade of Nox-derived ROS formation, as
      well as blockade of AGE formation and inhibitors of RAGE activation. These
      strategies may provide superior protection against the deleterious effects of
      diabetes on the vasculature. 

PMID- 24687631
TI  - Mother's awareness and attitudes towards prenatal screening for Down syndrome in
      Muslim Moroccans.
AB  - BACKGROUND: Abortion is prohibited and penalized in Morocco. On the other hand,
      there is no strategy or consensus for prenatal screening for Down syndrome (DS)
      included into the Moroccan pregnancy monitoring national program. OBJECTIVES:
      This study aims to explore the awareness and attitudes of women who have a child
      with DS regarding prenatal screening for DS. PATIENTS AND METHODS: This is an
      observational study based on a knowledge, attitude, and practice survey. RESULTS:
      Fifty women who have a child with DS agreed to participate in this survey.
      Although nearly two-thirds of women had not heard of DS or knew what prenatal
      screening is prior to the birth of the affected child, the majority felt that
      screening for DS would be useful in the first (84%) or second (90%) trimester. In
      line with this, most responders would agree to undergo first trimester (84%) or
      second trimester (80%) screening in a future pregnancy. Most (94%) of the women
      felt that information on DS screening should be provided to all Moroccan women in
      early pregnancy and that a public health program for prenatal screening should be
      established (94%). Deficit in knowledge was detected in awareness that first
      trimester ultrasound may allow screening for DS. CONCLUSION: Women who have a
      child with DS have low awareness of existing screening tests for the condition
      but have a positive attitude towards them.

PMID- 24687633
TI  - Calcitriol enhances fat synthesis factors and calpain activity in co-cultured
      cells.
AB  - We have conducted an in vitro experiment to determine whether calcitriol can act
      as a fat synthesizer and/or meat tenderizer when skeletal muscle cells, adipose
      tissue, and macrophages are co-cultured. When co-cultured, pro-inflammatory
      cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)
      expression increased, whereas decreased anti-inflammatory cytokine (IL-10 and IL
      15) expression decreased in both C2C12 and 3T3-L1 cells. Calcitriol increased
      reactive oxygen species (ROS) production in the media. While adiponectin gene
      expression decreased, leptin, resistin, CCAAT-enhancer-binding protein-beta
      (C/EBP-beta), and peroxisome proliferator-activated receptor gamma (PPAR-gamma)
      gene expression was significantly (P < 0.047) increased with calcitriol in 3T3-L1
      cells co-cultured with two different cell types. Inducible nitric oxide synthase
      (iNOS) protein levels were also stimulated in the C2C12 and 3T3-L1 cells, but
      arginase l was attenuated by calcitriol. Cacitriol highly amplified (P = 0.008) u
      calpain gene expression in co-cultured C2C12 cells. The results showed an overall
      increase in pro-inflammatory cytokines and a decrease in anti-inflammatory
      cytokines of C2C12 and 3T3-L1 cells with calcitriol in co-culture systems. u
      Calpain protein was also augmented in differentiated C2C12 cells with calcitriol.
      These findings suggest that calcitriol can be used as not only fat synthesizer,
      but meat tenderizer, in meat-producing animals.

PMID- 24687634
TI  - Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients
      with cognitive disorders diagnosed according to NIA-AA criteria.
AB  - OBJECTIVES: The purpose of this study was to clarify the concordance of
      diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose
      (FDG) positron emission tomography (PET) and brain perfusion single photon
      emission computed tomography (SPECT) in patients with Alzheimer's disease (AD)
      who were diagnosed according to the research criteria of the National Institute
      of Aging-Alzheimer's Association Workshop. METHODS: Fifty-five patients with "AD
      and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were
      evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during
      an 8-week period. Three radiologists independently graded the regional uptake in
      the frontal, temporal, parietal, and occipital lobes as well as the
      precuneus/posterior cingulate cortex in both images. Kappa values were used to
      determine the interobserver reliability regarding regional uptake. RESULTS: The
      regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD
      SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT
      agreement in the occipital lobes was not significant. The frontal, temporal, and
      parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT
      in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate
      cortex did not show good correlations. The diagnostic accuracy rates of "AD and
      MCI" ranged from 60% to 70% in both of the techniques. CONCLUSIONS: The degree of
      uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in
      the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG
      PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the
      National Institute of Aging-Alzheimer's Association Workshop criteria, were
      nearly identical.

PMID- 24687635
TI  - Titanium-catalyzed hydroalumination of conjugated dienes: access to fulvene
      derived allylaluminium reagents and their diastereoselective reactions with
      carbonyl compounds.
AB  - The described titanium-catalyzed hydroalumination of conjugated dienes opens up a
      new way to allylaluminium reagents. The reaction is carried out by using
      diisobutylaluminium hydride (DIBAL-H) and a catalytic amount of [Cp2TiCl2] (Cp =
      cyclopentadienyl). When applied to mono- and disubstitued pentafulvenes, this
      reaction proceeds in a highly endocyclic manner. The formed allylaluminium
      compounds react regio- and stereoselectively with both aldehydes and ketones to
      afford homoallylic alcohols that are suitable synthons for functionalized
      cyclopentanones. An extension of this methodology to simple dienes was also
      investigated. In the proposed mechanism, the initially formed bimetallic species
      (Ti/Al) are involved in the two possible catalytic cycles with a direct
      hydroalumination or/and a hydrotitanation followed by a titanium to aluminium
      transmetallation.

PMID- 24687636
TI  - Determinants of hemoglobin variability in stable peritoneal dialysis patients.
AB  - PURPOSE: Significant within-patient hemoglobin (Hb) level variability is well
      recognized in particularly hemodialysis patients. Several factors such as
      hospitalizations, intercurrent diseases and IV iron therapy are found to be
      related to Hb variability (Hb-var). In this observational study, we aimed to
      identify predictors and outcome of Hb-var in peritoneal dialysis (PD) patients
      without hospitalization, intercurrent disease and IV iron therapy during the
      study period. METHODS: All patients were in the maintenance phase of short-acting
      erythropoiesis-stimulating agents (ESAs) therapy. The target range of Hb was 11
      12 g/dL according to KDOQI Guidelines in 2007. The desired range of Hb was 11
      12.5 g/dL. Patients' demographic and laboratory data were collected at baseline.
      Atherosclerotic disease was assessed using carotid intima-media thickness (CIMT).
      We assessed Hb variability with various methods using SD Hbmean, SD Hbrange and
      the velocity of Hb change. Hb deflectpositive, Hb deflectnegative, Hb values and
      ESA dosing were recorded monthly for 6 months. RESULTS: This study included 50
      prevalent PD patients (mean age 46.9 +/- 13.7 years, 25 women). The mean velocity
      of Hb change was negatively correlated with age and positively correlated with
      frequent ESA dose changes. Higher albumin and residual renal function (RRF) were
      also positively correlated with Hb deflectpositive. Patients with CIMT >=0.7 cm
      had lower SD Hb range compared to CIMT <0.7 cm. Cumulative survival was better in
      patients with Hb levels consistently >=10 g/dL compared to patients who had Hb
      <10 g/dL for at least 1 month. However, Hb-var was not associated with mortality.
      CONCLUSIONS: In PD patients without hospitalization, intercurrent disease(s) or
      IV iron therapy, young age, higher albumin or RRF and lower CIMT were associated
      with greater oscillations in response to ESA therapy. Careful and appropriate ESA
      dose changes considering these parameters could minimize Hb variability in these
      patients.

PMID- 24687638
TI  - Professor Dr. Helmut Coper December 30, 1925-August 30, 2013. Professor for
      neuropsychopharmacology, FU Berlin (1967-94).

PMID- 24687637
TI  - Aspirin use and the risk of prostate cancer: a meta-analysis of 24 epidemiologic
      studies.
AB  - PURPOSE: Several epidemiologic studies were performed to clarify the protective
      effect of regular aspirin use on prostate cancer risk; however, the results
      remain controversial. Therefore, we conducted this meta-analysis to assess the
      association between regular aspirin use and risk of prostate cancer. METHODS:
      Electronic databases including PubMed, EMBASE and Cochrane Library were searched
      between January 1966 and April 2013 to identify eligible studies. Pooled relative
      ratios (RRs) and 95 % confidence intervals (CIs) were computed to assess the
      influence of aspirin use on prostate cancer risk. All statistical tests were two
      sided. RESULTS: A total of 24 observational studies including 14 case-control
      studies and 10 cohort studies were eligible for this meta-analysis. Regular
      aspirin use was associated with reduction in overall and advanced prostate cancer
      risk (pooled RR 0.86, 95 % CI 0.81-0.92; pooled RR 0.83, 95 % CI 0.75-0.91,
      respectively). When we restricted our analyses to studies with long-time regular
      aspirin use (equal or more than 4 years), reverse association became stronger
      (pooled RR 0.82, 95 % CI 0.72-0.93; pooled RR 0.70, 95 % CI 0.55-0.90,
      respectively). CONCLUSIONS: Our findings suggest that regular, especially long
      time regular aspirin use may reduce the risk of overall and advanced prostate
      cancer. Considering the limitation of included studies, further well-designed
      large-scaled cohort studies and RCTs are required to draw more definitive
      conclusions.

PMID- 24687630
TI  - Pathophysiology of glia in perinatal white matter injury.
AB  - Injury to the preterm brain has a particular predilection for cerebral white
      matter. White matter injury (WMI) is the most common cause of brain injury in
      preterm infants and a major cause of chronic neurological morbidity including
      cerebral palsy. Factors that predispose to WMI include cerebral oxygenation
      disturbances and maternal-fetal infection. During the acute phase of WMI,
      pronounced oxidative damage occurs that targets late oligodendrocyte progenitors
      (pre-OLs). The developmental predilection for WMI to occur during prematurity
      appears to be related to both the timing of appearance and regional distribution
      of susceptible pre-OLs that are vulnerable to a variety of chemical mediators
      including reactive oxygen species, glutamate, cytokines, and adenosine. During
      the chronic phase of WMI, the white matter displays abberant regeneration and
      repair responses. Early OL progenitors respond to WMI with a rapid robust
      proliferative response that results in a several fold regeneration of pre-OLs
      that fail to terminally differentiate along their normal developmental time
      course. Pre-OL maturation arrest appears to be related in part to inhibitory
      factors that derive from reactive astrocytes in chronic lesions. Recent high
      field magnetic resonance imaging (MRI) data support that three distinct forms of
      chronic WMI exist, each of which displays unique MRI and histopathological
      features. These findings suggest the possibility that therapies directed at
      myelin regeneration and repair could be initiated early after WMI and monitored
      over time. These new mechanisms of acute and chronic WMI provide access to a
      variety of new strategies to prevent or promote repair of WMI in premature
      infants.

PMID- 24687639
TI  - In memoriam Professor Dr. Helmut Coper.

PMID- 24687640
TI  - The influence of 8 and 16 mg nicotine patches on sleep in healthy non-smokers.
AB  - AIM AND METHODS: The purpose of this study was to determine whether sleep changes
      are a consequence of nicotine presence or withdrawal during the night, we
      examined 66 healthy non-smokers (33 males, 33 females, age: 20-25 years) after an
      adaptation night in a sleep laboratory setting. Subjects were randomized to
      receive placebo or either 8 or 16 mg nicotine patches during the day or during
      the night in a double blind, parallel group design. RESULTS: The 16 mg nicotine
      patch applied during the night caused a reduced sleep period time and sleep
      efficiency as well as an increased wake time. A reduced REM-sleep latency and
      subjective sleep quality rating were found in subjects receiving nicotine during
      the night. Arousals, apneas and periodic leg movements were not affected by
      nicotine. DISCUSSION: This study documents insomnia-like sleep changes in healthy
      non-smokers caused by nicotine in a dose-dependent manner. There was no evidence
      for sleep-related withdrawal symptoms after 13 h of nicotine application.

PMID- 24687641
TI  - Computerized breast mass detection using multi-scale Hessian-based analysis for
      dynamic contrast-enhanced MRI.
AB  - This study aimed to investigate a computer-aided system for detecting breast
      masses using dynamic contrast-enhanced magnetic resonance imaging for clinical
      use. Detection performance of the system was analyzed on 61 biopsy-confirmed
      lesions (21 benign and 40 malignant lesions) in 34 women. The breast region was
      determined using the demons deformable algorithm. After the suspicious tissues
      were identified by kinetic feature (area under the curve) and the fuzzy c-means
      clustering method, all breast masses were detected based on the rotation
      invariant and multi-scale blob characteristics. Subsequently, the masses were
      further distinguished from other detected non-tumor regions (false positives).
      Free-response operating characteristics (FROC) curve and detection rate were used
      to evaluate the detection performance. Using the combined features, including
      blob, enhancement, morphologic, and texture features with 10-fold cross
      validation, the mass detection rate was 100 % (61/61) with 15.15 false positives
      per case and 91.80 % (56/61) with 4.56 false positives per case. In conclusion,
      the proposed computer-aided detection system can help radiologists reduce inter
      observer variability and the cost associated with detection of suspicious lesions
      from a large number of images. Our results illustrated that breast masses can be
      efficiently detected and that enhancement and morphologic characteristics were
      useful for reducing non-tumor regions. 

PMID- 24687642
TI  - Neural network ensemble based CAD system for focal liver lesions from B-mode
      ultrasound.
AB  - A neural network ensemble (NNE) based computer-aided diagnostic (CAD) system to
      assist radiologists in differential diagnosis between focal liver lesions (FLLs),
      including (1) typical and atypical cases of Cyst, hemangioma (HEM) and metastatic
      carcinoma (MET) lesions, (2) small and large hepatocellular carcinoma (HCC)
      lesions, along with (3) normal (NOR) liver tissue is proposed in the present
      work. Expert radiologists, visualize the textural characteristics of regions
      inside and outside the lesions to differentiate between different FLLs,
      accordingly texture features computed from inside lesion regions of interest
      (IROIs) and texture ratio features computed from IROIs and surrounding lesion
      regions of interests (SROIs) are taken as input. Principal component analysis
      (PCA) is used for reducing the dimensionality of the feature space before
      classifier design. The first step of classification module consists of a five
      class PCA-NN based primary classifier which yields probability outputs for five
      liver image classes. The second step of classification module consists of ten
      binary PCA-NN based secondary classifiers for NOR/Cyst, NOR/HEM, NOR/HCC,
      NOR/MET, Cyst/HEM, Cyst/HCC, Cyst/MET, HEM/HCC, HEM/MET and HCC/MET classes. The
      probability outputs of five class PCA-NN based primary classifier is used to
      determine the first two most probable classes for a test instance, based on which
      it is directed to the corresponding binary PCA-NN based secondary classifier for
      crisp classification between two classes. By including the second step of the
      classification module, classification accuracy increases from 88.7 % to 95 %. The
      promising results obtained by the proposed system indicate its usefulness to
      assist radiologists in differential diagnosis of FLLs. 

PMID- 24687643
TI  - iPad-based patient briefing for radiological examinations-a clinical trial.
AB  - To analyze if an iPad-based patient briefing can serve as a digital alternative
      to conventional documentations prior to radiological examinations. One hundred
      one patients referred for routine MRI were randomized into two groups, who
      underwent iPad-based and classic written briefing in opposite order. For each
      briefing completion time, completeness and correctness were noted. Patient's
      knowledge about the content of either briefing modality was subsequently tested.
      The influence of patient-related factors on the performance of the electronic
      briefing (EB) was analyzed. Finally, the patient's subjective impression of the
      EB was assessed. The mean durations were 4.4 +/- 2.2 min for EB and 1.7 +/- 1.3
      min for the classic briefing (p < 0.01). All iPad briefings were returned
      entirely filled out, whereas 11 % of the classic forms were returned with missing
      data. No significant differences in memorization of the briefing's information
      were objectified. There was a positive correlation between the duration of EB and
      age (r = 0.53; p < 0.01), whereas a negative correlation was found between
      computer skills and patient's age (r = -0.55; p < 0.01) or duration of EB (r = 
      0.62; p < 0.01). More than half of the study patients would prefer EB in the
      future; another 29 % had no preference at all. Patient briefing on iPads
      transfers the information for the patients equally well compared to the classic
      written approach. Although iPad briefing took patients longer to perform, the
      majority would prefer it to written consent briefings in the future.
      Nevertheless, measures have to be undertaken to improve the overall acceptance
      and performance. 

PMID- 24687645
TI  - Renal nerve ablation for resistant hypertension: how did we get here, present
      status, and future directions.

PMID- 24687644
TI  - 18beta-glycyrrhetinic acid attenuates anandamide-induced adiposity and high-fat
      diet induced obesity.
AB  - SCOPE: Previous reports suggest that licorice extract has various metabolically
      beneficial effects and may help to alleviate adiposity and hyperlipidemia.
      However, underlying anti-obesity mechanisms still remain elusive. Moreover, it is
      unknown which single ingredient in licorice extract would mediate such effects.
      We aimed to demonstrate that licorice extract and its active ingredients can
      inhibit adipocyte differentiation and fat accumulation. METHODS AND RESULTS:
      18beta-glycyrrhetinic acid (18beta-GA) alleviated the effects of CB1R agonist,
      anandamide (AEA) on CB1R signaling in a concentration-dependent manner.
      Consistently, 18beta-GA suppressed AEA-induced adipocyte differentiation in 3T3
      L1 cells through the downregulation of AEA-induced MAPK activation and expression
      of adipogenic genes including C/EBP-alpha and PPAR-gamma. The protein levels of
      fatty acid synthase and stearoyl-CoA desaturase 1 were also decreased and the
      phosphorylation of acetyl-CoA carboxylase was increased in 18beta-GA pretreated
      cells. The supplementation of 18beta-GA significantly lowered body weight, fat
      weight, and plasma lipids levels in obese animal models. CONCLUSION: These
      results may provide a novel insight into the molecular mechanism involved in anti
      adipogenic and anti-obesity effects of 18beta-GA by suppressing the activation of
      CB1R induced by AEA. Thus, 18beta-GA may exert beneficial effects against obesity
      related metabolic disorders.

PMID- 24687647
TI  - Coronary magnetic resonance angiography in heterotopic heart transplant
      recipient.

PMID- 24687648
TI  - Twist and shout: acute right ventricular failure secondary to cardiac herniation
      and pulmonary artery compression.

PMID- 24687649
TI  - Cardiology Patient Page. On the possible link between vitamin D deficiency and
      cardiovascular disease: should we D-lighten our lives?

PMID- 24687651
TI  - Letter by Chyrchel et al regarding article, "unexpected effect of proton pump
      inhibitors: elevation of the cardiovascular risk factor asymmetric
      dimethylarginine".

PMID- 24687652
TI  - Letter by Montenegro and Lundberg regarding article, "unexpected effect of proton
      pump inhibitors: elevation of the cardiovascular risk factor asymmetric
      dimethylarginine".

PMID- 24687653
TI  - Letter by Pinheiro et al regarding article, "unexpected effect of proton pump
      inhibitors: elevation of the cardiovascular risk factor asymmetric
      dimethylarginine".

PMID- 24687654
TI  - Response to letters regarding article, "unexpected effect of proton pump
      inhibitors: elevation of the cardiovascular risk factor asymmetric
      dimethylarginine".

PMID- 24687656
TI  - Outcomes of surgery for chronic exertional compartment syndrome in a military
      population.
AB  - AIM: To determine the outcome following fasciectomy for chronic exertional
      compartment syndrome (CECS) in the UK military, and the association between
      presurgical intramuscular pressure (IMP) and outcome. METHODS: All patients who
      underwent fasciectomy for anterior CECS were identified between 2007 and 2010.
      Presurgery and postsurgery military medical grading for leg function was
      extracted from the medical records system. The Wilcoxon signed-rank test compared
      grades before and after surgery. Spearman's rank correlation examined the
      relationship between IMP and outcome. RESULTS: Presurgery and postsurgery grading
      was available for 63% of patients. These patients had significantly better leg
      function after surgery (Z=-3.63, p<0.001). Of these, 49% improved by at least one
      grade, 36% showed no improvement in grading and 15% had a poorer outcome. There
      were no significant correlations between IMP and outcome. CONCLUSIONS: A large
      proportion of patients do not return to full fitness following fasciectomy in the
      military population. This is in line with a recent study in the US military, but
      conflicts with most civilian reports. The reasons for these differences are not
      clear. Furthermore, the lack of a relationship between IMP and outcome questions
      the role of pressure in this condition. These results suggest that the role of
      postoperative rehabilitation protocols and other conservative options should be
      explored.

PMID- 24687658
TI  - The European Respiratory Society plans its future: the 2013-2018 strategic plan.

PMID- 24687659
TI  - The European Union standards for tuberculosis care: do they need an update?

PMID- 24687660
TI  - Processed meat consumption and lung health: more evidence for harm.

PMID- 24687661
TI  - Question everything.

PMID- 24687662
TI  - COPD assessment: I, II, III, IV and/or A, B, C, D.

PMID- 24687663
TI  - Microalbuminuria as a potential novel cardiovascular biomarker in patients with
      COPD.

PMID- 24687664
TI  - Activin-A: active in inflammation in COPD.

PMID- 24687665
TI  - Air pollution and acute exacerbations of idiopathic pulmonary fibrosis: back to
      miasma?

PMID- 24687666
TI  - Measuring health in pulmonary hypertension: emphasising the right end-point?

PMID- 24687667
TI  - Carbon monoxide diffusing capacity and the complexity of diagnosis in pulmonary
      arterial hypertension.

PMID- 24687668
TI  - Treatment of lymphangioleiomyomatosis: building evidence in orphan diseases.

PMID- 24687669
TI  - From the museum: The art of thinking. Part two: knowing.

PMID- 24687670
TI  - Lack of clinically relevant differences between combination therapy and
      monotherapy in COPD.

PMID- 24687671
TI  - Lack of clinically relevant differences between combination therapy and
      monotherapy in COPD.

PMID- 24687672
TI  - Multicomponent indices to predict survival in COPD.

PMID- 24687673
TI  - Multicomponent indices to predict survival in COPD.

PMID- 24687674
TI  - Simvastatin inhibits smoke-induced airway epithelial injury: implications for
      COPD therapy.

PMID- 24687675
TI  - Simvastatin inhibits smoke-induced airway epithelial injury: implications for
      COPD therapy.

PMID- 24687676
TI  - Risk factors for pulmonary tuberculosis in community-acquired pneumonia.

PMID- 24687677
TI  - Risk factors for pulmonary tuberculosis in community-acquired pneumonia.

PMID- 24687678
TI  - Ambulatory management of large primary spontaneous pneumothorax.

PMID- 24687684
TI  - Effects of a caloric restriction weight loss diet on tryptophan metabolism and
      inflammatory biomarkers in overweight adults.
AB  - PURPOSE: Recent data suggest that chronic low-grade inflammation, a
      characteristic of obesity, is associated with altered tryptophan (Trp) and
      tyrosine (Tyr) metabolism and plays a role in neuropsychiatric symptoms. The
      present study assessed the effect of an extreme short-term diet on Trp breakdown
      and inflammatory biomarkers in overweight adults. METHODS: Thirty-eight
      overweight participants (16 women, 22 men; average body mass index: 29 kg/m2,
      mean age 52.8 years) were randomized into two diet groups: a very low kcal diet
      group (VLCD; O 600 kcal/day, n = 21) and a low kcal diet group (LCD; O 1,200
      kcal/day, n = 17). Assays included the measurement of Trp, kynurenine (Kyn), and
      their ratio, neopterin, phenylalanine (Phe), Tyr, as biologic markers; leptin,
      plasma insulin, glucose, and homeostatic model assessment-insulin resistance; and
      interleukin 6, tumor necrosis factor alpha, and C-reactive protein, as
      biochemical and inflammatory markers at baseline and after 2 weeks of treatment.
      RESULTS: Weight loss diet lowered leptin levels in both groups by 46%, although
      not reaching significance. Trp and Kyn decreased significantly by 21 and 16% for
      VLCD and by 15 and 17% for the LCD group, respectively. A significant reduction
      in Phe was only seen after VLCD. Inflammatory biomarkers, neopterin, and Tyr were
      not significantly altered during the study period. Leptin was significantly
      correlated with Trp breakdown before and after the intervention (P < 0.02).
      CONCLUSIONS: Since disturbed metabolism of Trp affects biosynthesis of serotonin
      and might be associated with increased susceptibility for mood disturbances and
      carbohydrate craving, strategies to supplement Trp while dieting could be highly
      useful in treating uncontrolled weight gain or in preventing neuropsychiatric
      symptoms.

PMID- 24687685
TI  - Acid-mediated Lipinski's second rule: application to drug design and targeting in
      cancer.
AB  - With a predicted 382.4 per 100,000 people expected to suffer from some form of
      malignant neoplasm by 2015, and a current death toll of 1 out of 8 deaths
      worldwide, improving treatment and/or drug design is an essential focus of cancer
      research. Multi-drug resistance is the leading cause of chemotherapeutic failure,
      and delivery of anticancer drugs to the inside of cancerous cells is another
      major challenge. Fifteen years ago, in a completely different field in which
      improving drug delivery is the objective, the bioavailability of oral compounds,
      Christopher Lipinski formulated some rules that are still used by the
      pharmaceutical industry as rules of thumb to improve drug delivery to their
      target. Although Lipinski's rules were not formulated to improve delivery of
      antineoplastic drugs to the inside of cancer cells, it is interesting to note
      that the problems are similar. On the basis of the strong similarity between the
      fields, we discuss how they can be connected and how new drug targets can be
      defined in cancer.

PMID- 24687686
TI  - Effects of N,N-dimethyl-N-alkylamine-N-oxides on DOPC bilayers in unilamellar
      vesicles: small-angle neutron scattering study.
AB  - Small-angle neutron scattering data were collected from aqueous dispersions of
      unilamellar vesicles (ULVs) consisting of mixtures of 1,2-dioleoyl-sn-glycero-3
      phosphatidylcholine and a homologous series of N,N-dimethyl-N-alkylamine-N-oxides
      (CnNO, n = 12, 14, 16, and 18, where n is the number of carbon atoms in the alkyl
      chain). A modeling approach was applied to the neutron scattering curves to
      obtain the bilayer structural parameters. Particularly, the external (2)H2O/H2O
      contrast variation technique was carried out on pure dioleoylphosphatidylcholine
      (DOPC) ULVs to determine the hydrophilic region thickness [Formula: see text] =
      9.8 +/- 0.6 A. Consequently, the hydrocarbon region thickness [Formula: see
      text], the lateral bilayer area per one lipid molecule [Formula: see text], and
      the number of water molecules located in the hydrophilic region per one lipid
      molecule [Formula: see text] were obtained from single-contrast neutron
      scattering curves using the previously determined [Formula: see text]. The
      structural parameters were extracted as functions of [Formula: see text] (the
      CnNO:DOPC molar ratio) and n. The dependences [Formula: see text] provided the
      partial lateral areas of CnNOs ([Formula: see text]) and DOPC ([Formula: see
      text]) in bilayers. It was observed that the [Formula: see text]'s were constant
      in the investigated interval of [Formula: see text] and for n = 12, 14, and 16
      equal to 36.6 +/- 0.4 A(2), while [Formula: see text] increased to 39.4 +/- 0.4
      A(2). The bilayer hydrocarbon region thickness [Formula: see text] decreased with
      intercalation of each CnNO. This effect increased with [Formula: see text] and
      decreased with increasing CnNO alkyl chain length. The intercalation of C18NO
      changed the [Formula: see text] only slightly. To quantify the effect of CnNO
      intercalation into DOPC bilayers we fit the [Formula: see text] dependences with
      weighted linear approximations and acquired their slopes [Formula: see text].

PMID- 24687687
TI  - Type I NKT-cell-mediated TNF-alpha is a positive regulator of NLRP3 inflammasome
      priming.
AB  - The NLRP3 inflammasome plays a crucial role in the innate immune response to
      pathogens and exogenous or endogenous danger signals. Its activity must be
      precisely and tightly regulated to generate tailored immune responses. However,
      the immune cell subsets and cytokines controlling NLRP3 inflammasome activity are
      still poorly understood. Here, we have shown a link between NKT-cell-mediated TNF
      alpha and NLRP3 inflammasome activity. The NLRP3 inflammasome in APCs was
      critical to potentiate NKT-cell-mediated immune responses, since C57BL/6 NLRP3
      inflammasome-deficient mice exhibited reduced responsiveness to alpha
      galactosylceramide. Importantly, NKT cells were found to act as regulators of
      NLRP3 inflammasome signaling, as NKT-cell-derived TNF-alpha was required for
      optimal IL-1beta and IL-18 production by myeloid cells in response to alpha
      galactosylceramide, by acting on the NLRP3 inflammasome priming step. Thus, NKT
      cells play a role in the positive regulation of NLRP3 inflammasome priming by
      mediating the production of TNF-alpha, thus demonstrating another means by which
      NKT cells control early inflammation. 

PMID- 24687688
TI  - Acute pain experience in individuals with autism spectrum disorders: a review.
AB  - In addition to the diagnostic criteria for autism spectrum disorder, a number of
      clinically important comorbid complaints, including sensory abnormalities, are
      also discussed. One difference often noted in these accounts is hyposensitivity
      to pain; however, evidence for this is limited. The purpose of the current review
      therefore was to examine sensitivity to pain of individuals with autism spectrum
      disorder. This review is interested in reports which consider differences in
      subjective experience of pain (i.e. different pain thresholds) and differences in
      behavioural response to pain (i.e. signs of pain-related distress). Studies were
      included if they were conducted with human subjects, included a clearly diagnosed
      autism spectrum disorder population and reported data pertaining to pain
      experience relative to the neurotypical population. Studies were classified as
      being self/parent report, clinical observations, observations of response to
      medical procedures or experimental examination of pain. Both self/parent report
      and clinical observations appeared to report hyposensitivity to pain, whereas
      observations of medical procedures and experimental manipulation suggested normal
      or hypersensitive responses to pain. This review suggests that contrary to
      classical reports, individuals with autism spectrum disorder do not appear to
      have systematically altered pain responses or thresholds. More systematic
      experimental examination of this area is needed to understand responses to pain
      of individuals with autism spectrum disorder. 

PMID- 24687689
TI  - Susceptibility in field populations of codling moth, Cydia pomonella (L.)
      (Lepidoptera: Tortricidae), in Ontario and Quebec apple orchards to a selection
      of insecticides.
AB  - BACKGROUND: Codling moth is a major pest of pome fruit worldwide. Insecticide
      resistance has become a widespread pest management issue. However, the current
      status of insecticide resistance in Ontario and Quebec codling moth populations
      is unknown. RESULTS: Codling moth populations were collected from 27 orchards in
      Ontario and Quebec from 2008 to 2010. A series of laboratory bioassays were
      performed to establish baseline susceptibility of adults and larvae to azinphos
      methyl, thiacloprid, chlorantraniliprole and methoxyfenozide. Adult codling moth
      percentage mortality ranged from 22 to 97% and from 21 to 85% when exposed to
      topical bioassays using azinphos-methyl and thiacloprid respectively. Azinphos
      methyl LC50 values from three selected orchards were ca fivefold greater than
      those from an insecticide-susceptible population. Neonate larva percentage
      mortality ranged from 5 to 50%, from 15 to 65%, from 90 to 100% and from 10 to
      40% when exposed to diet bioassays using azinphos-methyl, thiacloprid,
      chlorantraniliprole and methoxyfenozide respectively. CONCLUSION: Based on the
      response of the field-collected populations, resistance development to some
      registered insecticides was evident in some Ontario and Quebec populations. With
      the present status of insecticide resistance documented in these regions,
      modifications to codling moth management strategies should be initiated before
      changes in field efficacy occur.

PMID- 24687690
TI  - Assessment of long-term wastewater irrigation impacts on the soil geochemical
      properties and the bioaccumulation of heavy metals to the agricultural products.
AB  - An extensive field survey was employed for assessing the impacts of long-term
      wastewater irrigation of forage crops and orange orchards in three suburban
      agricultural areas in Cyprus (areas I, II, and III), as compared to rainfed
      agriculture, on the soil geochemical properties and the bioaccumulation of heavy
      metals (Zn, Ni, Mn, Cu, Co) to the agricultural products. Both ryegrass fields
      and orange orchards in areas I and II were continuously wastewater irrigated for
      10 years, whereas clover fields in area III for 0.5, 4, and 8 years. The results
      revealed that wastewater reuse for irrigation caused a slight increase in soil
      salinity and Cl(-) content in areas I and II, and a remarkable increase, having
      strong correlation with the period in which wastewater irrigation was practiced,
      in area III. Soil salinization in area III was due to the high electrical
      conductivity (EC) of the wastewater applied for irrigation, attributed to the
      influx of seawater to the sewage collection network in area III. In addition, the
      wastewater irrigation practice resulted in a slight decrease of the soil pH
      values in area III, while a subtle impact was identified regarding the CaCO3, Fe,
      and heavy metal content in the three areas surveyed. The heavy metal content
      quantified in the forage plants' above-ground parts was below the critical levels
      of phytotoxicity and the maximum acceptable concentration in dairy feed, whereas
      heavy metals quantified in orange fruit pulp were below the maximum permissible
      levels (MPLs). Heavy metal phytoavailability was confined due to soil properties
      (high pH and clay content), as evidenced by the calculated low transfer factor
      (TF). 

PMID- 24687691
TI  - Use of the land snail Helix aspersa for monitoring heavy metal soil contamination
      in Northeast Algeria.
AB  - The objective of this study was to investigate the impact of anthropogenic
      activities on soil quality using the land snail Helix aspersa as a bioindicator.
      Soil samples and snails were collected from several sites in Northeast Algeria
      during the summer and winter of 2010. All of the sites were chosen due to their
      proximity to industrial factories-a potential source of soil pollution via heavy
      metal contamination. The concentration of heavy metals (Pb, Cd, Mn, and Fe) in
      soil samples was analyzed using atomic absorption spectrophotometry. Activity
      levels of glutathione S-transferase (GST) and acetylcholinesterase (AChE),
      indicators of oxidative stress and neurotoxicity, respectively, were measured in
      snails collected from each site. GST and AChE activity were found to vary between
      sites and by season. The highest levels of GST activity were registered during
      the summer at sites closest to potential sources of pollution. AChE activity
      levels also peaked during the summer with the highest values recorded at the site
      in El Hadjar. These increased levels of bioindicative stress response correlated
      with increasing metal concentration in soil samples collected at each site. 

PMID- 24687692
TI  - Assessment of organochlorine pesticide residues in Indian flue-cured tobacco with
      gas chromatography-single quadrupole mass spectrometer.
AB  - Presence of pesticide residues in tobacco increases health risk of both active
      and passive smokers, apart from the imminent potential health problems associated
      with it. Thus, monitoring of pesticide residue is an important issue in terms of
      formulating stringent policies, enabling global trade and safeguarding the
      consumer's safety. In this study, a gas chromatography-single quadrupole mass
      spectrometry (GC-MS) method based upon quantifier-qualifier ions (m/z) ratio was
      employed for detecting and assessing ten organochlorine pesticide residues (alpha
      HCH, beta-HCH, gamma-HCH, delta-HCH, 2,4-DDT, 4,4-DDT, endrin, alpha-endosulfan,
      beta-endosulfan and endosulfan sulphate) in 152 flue-cured (FC) tobacco leave
      samples from two major tobacco growing states, Karnataka and Andhra Pradesh, of
      India. In the majority of samples, pesticide residue levels were below the limit
      of quantification (LOQ). In few samples, pesticide residues were detected and
      they found to comply with the guidance residue levels (GRL) specifications of the
      Cooperation Center for Scientific Research Relative to Tobacco (CORESTA).
      Detection of the phase out pesticides like DDT/HCH might be due to transfer of
      persistent residues from the environmental components to the plant. This is the
      first report on these ten organochlorine pesticide residues in Indian FC tobacco.

PMID- 24687693
TI  - Self-reported utilization of mental health services in the adult German
      population--evidence for unmet needs? Results of the DEGS1-Mental Health Module
      (DEGS1-MH).
AB  - This paper provides up-to-date data on service use for mental health problems and
      disorders among adults aged 18-79 years in Germany derived from the Mental Health
      Module of the German Health Interview and Examination Survey for Adults (DEGS1
      MH; N=4483). Data are based exclusively on self-report. Respondents were examined
      by clinically trained interviewers with a modified version of the Composite
      International Diagnostic Interview DIA-X/M-CIDI to assess diagnoses according to
      the criteria of DSM-IV-TR. Service use, i.e. contact to mental health care
      services, due to mental health problems was assessed for the past 12 months and
      lifetime, by type of sector and type of institution. Among respondents with a 12
      month diagnosis of a mental disorder, 23.5% of the women and 11.6% of the men
      reported any service use in the past 12 months. Service use depends on type of
      diagnosis, comorbidity and socio-demographic characteristics. Lowest 12-month
      utilization rates were found for substance use disorders (15.6%; lifetime use
      37.3%), highest for psychotic disorders (40.5%; lifetime 72.1%). Further, a
      considerable time lap was found between disorder onset and subsequent service use
      among the majority of cases with anxiety and mood disorders. This paper provides
      self-reported epidemiological data on mental health service use in Germany,
      complementing administrative statistics and the predecessor mental health module
      of the German Health Interview and Examination Survey (GHS-MHS) from 1998.
      Despite considerable changes in the mental health field in Germany and the
      existence of a comprehensive mental health care system without major financial
      barriers, we find no indications of substantially higher utilization rates for
      mental disorders as compared to other comparable European countries. Further, no
      indications of major overall changes in utilization rates are apparent. To
      pinpoint areas with unmet needs, more detailed analyses of the data are needed
      taking into account type, frequency, and adequacy of service use and treatment of
      mental disorders. Appropriately matched comparisons with the GHS-MHS are needed
      to identify changes in patterns of utilization and interventions by type of
      disorder.

PMID- 24687694
TI  - Modifications of the homeostasis model assessment of insulin resistance index
      with age.
AB  - The aim of the study was to analyze the association between aging and insulin
      resistance estimated by the homeostasis model assessment of insulin resistance
      (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross
      sectional study including 4,948 subjects, comprising a representative sample of
      the adult Spanish population; (2) the Pizarra study is a population-based cohort
      study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at
      baseline and 714 completed the 6-year follow-up study. Study variables included a
      clinical and demographic structured survey, a lifestyle survey, a physical
      examination, and an oral glucose tolerance test in subjects without diabetes. In
      the Di@bet.es study overall, an increase occurred in blood glucose until the age
      of 50, after which it remained stable (data adjusted for gender, body mass index,
      abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age
      (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p <
      0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with
      age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra
      study, the HOMA-IR was significantly lower after 6-year follow-up in the whole
      study population. Subjects with a HOMA-IR level higher than the 75th percentile
      at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2-3.9; p =
      0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not
      increase HOMA-IR levels, changes that might be related to higher rates of obesity
      and AGR in older subjects. The HOMA-IR was associated with an increased risk of
      developing type 2 diabetes 6 years later.

PMID- 24687695
TI  - The single-port concept: combining optical glucose measurement with insulin
      infusion.
AB  - The aim of this study was to develop a single-port system that combines glucose
      monitoring and insulin infusion. In a preclinical proof-of-concept trial, the
      performance of the glucose measurement at the site of insulin infusion was
      assessed. Glucose levels were clamped from 40 to 250 mg/dL by intravenous glucose
      infusion and subcutaneous insulin infusion via the glucose sensor. Sensor-glucose
      values correlated well with reference blood-glucose values, despite infusion at
      the site of glucose measurement. The average median ARE value was 21.6 +/- 5.7 %
      for sensors used for insulin infusion, 18.1 +/- 5.8 % for sensors used for NaCl
      infusion and 19.2 +/- 7.9 % for sensors without infusion. These preclinical in
      vivo results demonstrate that single-port glucose monitoring is feasible at the
      site of insulin infusion. 

PMID- 24687696
TI  - [Importance of air ambulances for the care of the severely injured].
AB  - BACKGROUND: In the late 1960s, helicopter emergency medical services (HEMS) were
      established because of the increasing number of severely injured in road traffic
      accidents. It was initially thought to bring the doctor to the patient quickly.
      AIM: Today, the rescue helicopter covers the entire field of emergency medicine.
      By analyzing the databases of the TraumaRegister DGU(r) (2005-2011), the
      importance of the HEMS for the treatment of the severely injured was examined.
      RESULTS: The results showed that around 30 % of severely injured are allocated to
      hospitals by HEMS. In addition to regional differences, the level of the hospital
      also plays a particularly important role. The combination of the transfer by HEMS
      and treatment in a level I trauma center has a significantly positive effect on
      the survival rate of the patient, especially in patients with traumatic brain
      injury (TBI).

PMID- 24687697
TI  - Patient and process factors associated with all-cause 30-day readmission among
      patients with heart failure.
AB  - PURPOSE: To explore the patient and process factors associated with all-cause 30
      day readmission after heart failure (HF) hospitalization and develop
      recommendations to reduce readmissions of patients with HF. DATA SOURCES: A
      retrospective, cohort study of 239 patients ages 18 years and older was performed
      using electronic medical chart review. All patients were discharged from the
      medical center between July 1, 2009 and June 30, 2010 with a principal diagnosis
      of HF. Patient and process factors were compared in readmitted and non-readmitted
      groups. CONCLUSIONS: Renal failure/insufficiency was the only factor
      significantly associated with all-cause 30-day readmission among patients with
      HF. IMPLICATIONS FOR PRACTICE: Assessment of renal function during
      hospitalization will help identify patients with HF at high risk for all-cause 30
      day readmission. Give careful consideration to the timing of discharge of
      patients who appear otherwise ready for discharge but still have creatinine
      levels above their baseline. Careful follow-up is needed for patients with
      impaired renal function.

PMID- 24687698
TI  - Fluorescent amphiphilic PEG-peptide-PEG triblock conjugate micelles for cell
      imaging.
AB  - A fluorescent amphiphilic poly(ethylene glycol)-peptide-fluorophore-peptide
      poly(ethylene glycol) (PEG-Pep-F-Pep-PEG) triblock conjugate with a hydrophobic
      fluorophore moiety at the centre of the chain is synthesized by "grafting to"
      technique based on Schiff-base coupling chemistry. The conjugate is characterized
      by nuclear magnetic resonance (NMR), circular dichroism (CD), and fluorescence
      spectroscopy techniques. The aqueous solution of the triblock conjugate emits
      blue light and exhibits a fluorescence emission band at 430 nm. The amphiphilic
      conjugate molecules undergo self-assembly into micelles (D ~ 15-20 nm) in aqueous
      solution as confirmed from transmission electron microscopy (TEM) and dynamic
      light scattering (DLS). The critical aggregation concentration is determined by
      pyrene fluorescence assay and is found to be 0.051 mg mL(-1) . The highly stable
      and low toxic fluorescent PEG-Pep-F-Pep-PEG conjugate micelles are used for
      imaging of HeLa cells. 

PMID- 24687700
TI  - Rapid FEV1 decline, early COPD, and angiotensin-converting enzymes?

PMID- 24687699
TI  - Gliotoxin-induced swelling of astrocytes hinders diffusion in brain extracellular
      space via formation of dead-space microdomains.
AB  - One of the hallmarks of numerous life-threatening and debilitating brain diseases
      is cellular swelling that negatively impacts extracellular space (ECS) structure.
      The ECS structure is determined by two macroscopic parameters, namely tortuosity
      (lambda) and volume fraction (alpha). Tortuosity represents hindrance imposed on
      the diffusing molecules by the tissue in comparison with an obstacle-free medium.
      Volume fraction is the proportion of tissue volume occupied by the ECS. From a
      clinical perspective, it is essential to recognize which factors determine the
      ECS parameters and how these factors change in brain diseases. Previous studies
      demonstrated that dead-space (DS) microdomains increased lambda during ischemia
      and hypotonic stress, as these pocket-like structures transiently trapped
      diffusing molecules. We hypothesize that astrocytes play a key role in the
      formation of DS microdomains because their thin processes have concave shapes
      that may elongate as astrocytes swell in these pathologies. Here we selectively
      swelled astrocytes in the somatosensory neocortex of rat brain slices with a
      gliotoxin DL-alpha-Aminoadipic Acid (DL-AA), and we quantified the ECS parameters
      using Integrative Optical Imaging (IOI) and Real-Time Iontophoretic (RTI)
      diffusion methods. We found that alpha decreased and lambda increased during DL
      AA application. During recovery, alpha was restored whereas lambda remained
      elevated. Increase in lambda during astrocytic swelling and recovery is
      consistent with the formation of DS microdomains. Our data attribute to the
      astrocytes an important role in determining the ECS parameters, and indicate that
      extracellular diffusion can be improved not only by reducing the swelling but
      also by disrupting the DS microdomains.

PMID- 24687701
TI  - The prognostic value of the GAP model in chronic interstitial lung disease: the
      quest for a staging system.

PMID- 24687702
TI  - Primary ciliary dyskinesia and cystic fibrosis: different diseases require
      different treatment.

PMID- 24687704
TI  - Giants in chest medicine: Marvin I. Schwarz, MD, FCCP.

PMID- 24687705
TI  - Air travel and pneumothorax.
AB  - The number of medical emergencies onboard aircraft is increasing as commercial
      air traffic increases and the general population ages, becomes more mobile, and
      includes individuals with serious medical conditions. Travelers with respiratory
      diseases are at particular risk for in-flight events because exposure to lower
      atmospheric pressure in a pressurized cabin at cruising altitude may result in
      not only hypoxemia but also pneumothorax due to gas expansion within enclosed
      pulmonary parenchymal spaces based on Boyle's law. Risks of pneumothorax during
      air travel pertain particularly to those patients with cystic lung diseases,
      recent pneumothorax or thoracic surgery, and chronic pneumothorax. Currently
      available guidelines are admittedly based on sparse data and include
      recommendations to delay air travel for 1 to 3 weeks after thoracic surgery or
      resolution of the pneumothorax. One of these guidelines declares existing
      pneumothorax to be an absolute contraindication to air travel although there are
      reports of uneventful air travel for those with chronic stable pneumothorax. In
      this article, we review the available data regarding pneumothorax and air travel
      that consist mostly of case reports and retrospective surveys. There is clearly a
      need for additional data that will inform decisions regarding air travel for
      patients at risk for pneumothorax, including those with recent thoracic surgery
      and transthoracic needle biopsy. 

PMID- 24687706
TI  - Occupational hypersensitivity pneumonitis in a baker: a new cause.
AB  - Bakers are exposed daily to flour and may be susceptible to immunologic
      occupational diseases. A 30-year-old, nonsmoking, female baker was referred for
      progressive dyspnea on exertion, basal crackles on auscultation, restrictive lung
      function, decreased diffusing capacity of the lung for carbon monoxide, ground
      glass hyperdensities with a mosaic pattern on high-resolution CT scan, 25%
      lymphocytosis by BAL, and cellular chronic bronchiolitis with peribronchiolar
      interstitial inflammation by lung biopsy specimen. Cultures from flours isolated
      nine species, including Aspergillus fumigatus. Twenty-six antigens were tested.
      Serum-specific precipitins were found against A fumigatus, the flour mite Acarus
      siro, and total extracts from maize and oat. Outcome was favorable with cessation
      of occupational exposure to flours and transient therapy with prednisone and
      immunosuppressive agents. To our knowledge, this report is the first of a well
      documented case of hypersensitivity pneumonitis due to sensitization to fungi-
      and mite-contaminated flours. Hypersensitivity pneumonitis--and not only asthma
      and allergic rhinitis--should be suspected in bakers with respiratory symptoms.

PMID- 24687707
TI  - Mycobacterium brisbanense species nova isolated from a patient with chronic
      cavitary lung infection.
AB  - We describe the first case, to our knowledge, of Mycobacterium brisbanense
      species nova with the type strain W6743T (=ATCC 49938T=DSM 44680T) isolated from
      the lungs of a man with a 6-month history of productive cough and intermittent
      fever presenting with acute hypoglycemia. A CT scan of the thorax revealed
      multiple small nodules and consolidation over both lungs with cavitation. Sputum
      culture repeatedly grew M brisbanense species nova, a novel species never before
      isolated in Malaysia. The case met the American Thoracic Society criteria for the
      diagnosis of nontuberculous mycobacterial infection. There was dramatic clinical
      and radiologic response to treatment with an empirical combination of rifampicin,
      ethambutol, and levofloxacin and subsequently clarithromycin and levofloxacin
      once sensitivity was known. This report is the first, to our knowledge, of the
      pathogen isolated in a patient with chronic cavitary lung infection since it was
      first identified from an antral sinus in Brisbane, Queensland, Australia, and the
      first time it is isolated from a human subject in Malaysia.

PMID- 24687708
TI  - Arterial stiffness in COPD.
AB  - In patients with COPD, cardiovascular diseases are the most common concomitant
      chronic diseases, a leading cause of hospitalization, and one of the main causes
      of death. A close connection exists between COPD and cardiovascular diseases.
      Cardiovascular risk scores aim to predict the effect of cardiovascular
      comorbidities on COPD mortality, but there is a need to better characterize
      occult and suboccult cardiovascular disease, even in patients with mild to
      moderate COPD. Among various surrogate markers of cardiovascular risk, arterial
      stiffness plays a central role and is a strong independent predictor of
      cardiovascular events beyond classic cardiovascular risk factors. Its measurement
      is highly suitable, validated, and relatively easy to perform in routine COPD
      clinical practice. The growing awareness of the increased cardiovascular risk
      associated with COPD has led to a call for respiratory physicians to measure
      arterial pulse wave velocity in routine practice. Cross-sectional data establish
      elevated arterial stiffness as being independently linked to COPD. Candidate
      mechanisms have been proposed, but surprisingly, only limited data are available
      regarding the impact of the different COPD treatment modalities on arterial
      stiffness, although initial studies have suggested a significant positive impact.
      In this review, we present the various surrogate markers of cardiovascular
      morbidity in COPD and the central role of arterial stiffness and the underlying
      mechanisms explaining vascular remodeling in COPD. We also consider the
      therapeutic impact of COPD medications and exercise training on arterial
      stiffness and the assessments that should be implemented in COPD care and follow
      up. 

PMID- 24687709
TI  - Ethical dilemmas encountered with the use of extracorporeal membrane oxygenation
      in adults.
AB  - Extracorporeal membrane oxygenation (ECMO) can serve as a bridge to recovery in
      cases of acute reversible illness, a bridge to transplantation in circumstances
      of irreversible cardiac or respiratory failure, a bridge to ventricular assist
      device therapy in select cases of cardiac failure, or a bridge to decision when
      the prognosis remains uncertain. Recent advances in ECMO technology that allow
      for prolonged support with decreased complications, the development of mobile
      ECMO teams, the rapidity of initiation, and the growing body of evidence, much of
      which remains controversial, have led to a significant increase in the use of
      ECMO worldwide. This increasing use of a technology that is not a destination
      device in itself introduces many ethical dilemmas specific to this technology. In
      this article, we explore some of the ethical issues inherent in the decisions
      surrounding the initiation and withdrawal of ECMO by raising key questions and
      providing a framework for clinicians. We will address extracorporeal
      cardiopulmonary resuscitation, the inability to bridge a patient to transplant or
      recovery--the so-called "bridge to nowhere"--and the significance of
      resuscitation preferences in the setting of continual extracorporeal circulatory
      support.

PMID- 24687710
TI  - Parasites of the air passages.
AB  - Parasitic infestations affect millions of the world's population. Global
      immigration and climate change have led to changes in the natural distribution of
      parasitic diseases far removed from endemic areas. A broad spectrum of helminthic
      and protozoal parasitic diseases frequently affects the respiratory system. The
      wide varieties of clinical and radiographic presentations of parasitic diseases
      make the diagnosis of this entity challenging. Pulmonologists need to become
      familiar with the epidemiology, clinical presentation, pathophysiologic
      characteristics, and bronchoscopic findings to provide proper management in a
      timely fashion. This review provides a comprehensive view of both helminthic and
      protozoal parasitic diseases that affect the respiratory system, especially the
      airways. 

PMID- 24687711
TI  - The intelligent use of digital tools and social media in practice management.
AB  - The Internet has fundamentally transformed the way patients and health-care
      providers communicate and interact. The use of digital tools and social media
      platforms, such as blogs, Facebook, Instagram, and Twitter, have empowered
      patients to expand their health-care knowledge and have provided practitioners
      with new ways to gain knowledge, lead discussions, promote causes, and build
      relationships with patients and other providers. In this article, we discuss the
      difference between digital communication, static one-way digital presence, and
      two-way social media connections. We also describe ways to establish and foster
      your digital profile, review the benefits and risks of engaging professionally in
      social media, and describe ways in which digital and social media tools may prove
      useful in both reimbursement and practice management. 

PMID- 24687712
TI  - Innovative designs for the smart ICU: Part 3: Advanced ICU informatics.
AB  - This third and final installment of this series on innovative designs for the
      smart ICU addresses the steps involved in conceptualizing, actualizing, using,
      and maintaining the advanced ICU informatics infrastructure and systems. The
      smart ICU comprehensively and electronically integrates the patient in the ICU
      with all aspects of care, displays data in a variety of formats, converts data to
      actionable information, uses data proactively to enhance patient safety, and
      monitors the ICU environment to facilitate patient care and ICU management. The
      keys to success in this complex informatics design process include an
      understanding of advanced informatics concepts, sophisticated planning,
      installation of a robust infrastructure capable of both connectivity and
      interoperability, and implementation of middleware solutions that provide value.
      Although new technologies commonly appear compelling, they are also complicated
      and challenging to incorporate within existing or evolving hospital informatics
      systems. Therefore, careful analysis, deliberate testing, and a phased approach
      to the implementation of innovative technologies are necessary to achieve the
      multilevel solutions of the smart ICU. 

PMID- 24687713
TI  - A 76-year-old man with anemia, bone pain, and progressive dyspnea. Diagnosis:
      Bilateral myelomatous pleural effusions with extramedullary plasmacytomas.

PMID- 24687714
TI  - A 63-year-old man with a chronic cough and an endobronchial lesion. Diagnosis:
      Endobronchial hamartoma.

PMID- 24687718
TI  - Antimicrobial guidance in ventilator-associated pneumonia with routine
      endotracheal cultures.

PMID- 24687719
TI  - Response.

PMID- 24687720
TI  - Aerosolized colistin cost-effectiveness.

PMID- 24687721
TI  - Response.

PMID- 24687722
TI  - Prediction of postoperative lung function in patients with lung cancer: the role
      of quantitative CT imaging.

PMID- 24687723
TI  - Response.

PMID- 24687725
TI  - A teenager with fever and sore throat. Diagnosis: Lemierre syndrome.

PMID- 24687726
TI  - Access to the aeruginosin serine protease inhibitors through the nucleophilic
      opening of an oxabicyclo[2.2.1]heptane: total synthesis of microcin SF608.
AB  - Serine proteases play key roles in many biological processes and are associated
      with several human diseases such as thrombosis or cancer. During the search for
      selective inhibitors of serine proteases, a family of linear peptides named the
      aeruginosins was discovered in marine cyanobacteria. We herein report an entry
      route into the synthetically challenging core fragment of these natural products.
      Starting from the common oxabicyclic building block 11, we accessed the
      octahydroindole core of the aeruginosins, exemplified by the total synthesis of
      microcin SF608 (2). Key to the synthetic strategy is a highly efficient
      nucleophilic opening of an oxabicyclo[2.2.1]heptane producing the hydroindole
      motif of microcin SF608. Moreover, during the synthetic efforts we have observed
      an unusual regioselective epoxide reduction. Detailed experimental studies of
      this reaction led us to propose a mechanistic rationale involving intramolecular
      hydrogen atom delivery by a carbamate NH group to control the regioselectivity of
      the homolytic epoxide cleavage. 

PMID- 24687727
TI  - Isolation and propagation of neural stem cells in caprine (Capra hircus).
AB  - Neural stem cells (NSCs) can self-renew and give rise to neurons, astrocytes and
      oligodendrocytes; they are found in the nervous system of mammalian organisms,
      representing a promising resource for both fundamental research and therapeutics.
      There have been few investigations on NSCs in the livestock species. Therefore,
      we have successfully isolated and characterised NSCs from the foetal brain of a
      small domestic animal, the goat (called GNSCs). These cells from the foetal brain
      showed self-renewal, rapid proliferation with a population doubling time of 88 h,
      were morphologically homogeneous and maintained normal chromosome throughout the
      culture period. The cells expressed NSC-specific markers (Sox2, Pax6 and
      Mushashi), but were negative for CD34 and CD45. They were capable of multi
      differentiation into neurons, astrocytes, oligodendrocytes, as well as adipocytes
      and osteocytes. The availability of such cells may hold great interest for basic
      and applied neuroscience.

PMID- 24687728
TI  - Mass spectrometry imaging for visualizing organic analytes in food.
AB  - The demand for rapid chemical imaging of food products steadily increases. Mass
      spectrometry (MS) is featured by excellent molecular specificity of analysis and
      is, therefore, a very attractive method for chemical profiling. MS for food
      imaging has increased significantly over the past decade, aided by the emergence
      of various ambient ionization techniques that allow direct and rapid analysis in
      ambient environment. In this article, the current status of food imaging with MSI
      is reviewed. The described approaches include matrix-assisted laser
      desorption/ionization (MALDI), but emphasize desorption atmospheric pressure
      photoionization (DAPPI), electrospray-assisted laser desorption/ionization
      (ELDI), probe electrospray ionization (PESI), surface desorption atmospheric
      pressure chemical ionization (SDAPCI), and laser ablation flowing atmospheric
      pressure afterglow (LA-FAPA). The methods are compared with regard to spatial
      resolution; analysis speed and time; limit of detection; and technical aspects.
      The performance of each method is illustrated with the description of a related
      application. Specific requirements in food imaging are discussed.

PMID- 24687729
TI  - Forest type affects prey foraging of saddleback tamarins, Saguinus nigrifrons.
AB  - Callitrichids can persist in secondary forests where they may benefit from
      elevated prey abundance. However, how tamarins forage for prey in secondary
      forest compared to primary forest has not been examined. Using scan and focal
      sampling, we compared prey foraging and capture success of two groups of Saguinus
      nigrifrons in north-eastern Peru: one ranging in primary forest, the other with
      access to a 10-year-old anthropogenic secondary forest. There was a trend for
      more prey search in the secondary forest, but prey feeding, capture success and
      size were lower compared to the primary forest. Tamarins avoided the forest
      floor, used vertical supports less often and searched on a lower variety of
      substrates in the secondary forest. In the secondary forest, tamarins did not
      capture flushed prey, which make up a substantial part of the total prey captures
      biomass in primary forests. Reduced prey capture success is unlikely to reflect
      reduced prey availability, since more Orthoptera were found in secondary forest
      through ultrasonic surveys. Therefore, the prey search activity of S. nigrifrons
      in young secondary forests seemed rather opportunistic, presumably influenced by
      altered predation patterns, vegetation structure, as well as prey diversity.

PMID- 24687730
TI  - Specific targeting of atherosclerotic plaques in ApoE(-/-) mice using a new
      Camelid sdAb binding the vulnerable plaque marker LOX-1.
AB  - PURPOSE: Molecular imaging has the potential to provide quantitative information
      about specific biological aspects of developing atherosclerotic lesions. This
      requires the generation of reliable, highly specific plaque tracers. This study
      reports a new camelid single-domain antibody fragment (sdAb) targeting the Lectin
      like oxidized low-density lipoprotein receptor (LOX-1), a biomarker for the
      detection and molecular phenotyping of vulnerable atherosclerotic plaques.
      PROCEDURES: A camelid sdAb was generated and selected for high affinity binding
      to LOX-1. Ex vivo biodistribution and in vivo single photon emission computed
      tomography (SPECT)/computed tomography (CT) imaging studies were performed in
      wild-type mice and in fat-fed atherosclerotic apolipoprotein E-deficient mice
      with (99m)Tc-labeled sdAbs. Gamma-counting and autoradiography analyses were
      performed on dissected aorta segments with different degrees of plaque burden.
      The specificity of the LOX-1-targeting sdAb was evaluated by blocking with
      unlabeled sdAb or by comparison with a nontargeting (99m)Tc-labeled control sdAb.
      RESULTS: We generated a sdAb binding LOX-1 with a KD of 280 pM +/- 62 pM
      affinity. After (99m)Tc-labeling, the tracer had radiochemical purity higher then
      99 % and retained specificity in in vitro binding studies. Tracer blood clearance
      was fast with concomitant high kidney retention. At 3 h after injection, uptake
      in tissues other than plaques was low and not different than background,
      suggesting a restricted expression pattern of LOX-1. Conversely, uptake in aortic
      segments increased with plaque content and was due to specific LOX-1 binding. In
      vivo SPECT/CT imaging 160 min after injection in atherosclerotic mice confirmed
      specific targeting of LOX-1-expressing aortic plaques. CONCLUSIONS: The LOX-sdAb
      specifically targets LOX-1-expressing atherosclerotic plaques within hours after
      injection. The possibility to image LOX-1 rapidly after administration combined
      with the favourable biodistribution of a sdAb are beneficial for molecular
      phenotyping of atherosclerotic plaques and the generation of a future prognostic
      tracer.

PMID- 24687732
TI  - Semantic interference from distractor pictures in single-picture naming: evidence
      for competitive lexical selection.
AB  - Picture-naming studies have demonstrated interference from semantic-categorically
      related distractor words, but not from corresponding distractor pictures, and the
      lack of generality of the interference effect has been argued to challenge
      theories viewing lexical selection in speech production as a competitive process.
      Here, we demonstrate that semantic interference from context pictures does become
      visible, if sufficient attention is allocated to them. We combined picture naming
      with a spatial-cuing procedure. When participants' attention was shifted to the
      distractor, semantically related distractor pictures interfered with the
      response, as compared with unrelated distractor pictures. This finding supports
      models conceiving lexical retrieval as competitive (Levelt, Roelofs, & Meyer,
      1999) but is difficult to reconcile with the response exclusion hypothesis
      (Finkbeiner & Caramazza, 2006b) proposed as an alternative.

PMID- 24687731
TI  - CCR7 directs the recruitment of T cells into inflamed pancreatic islets of
      nonobese diabetic (NOD) mice.
AB  - Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease characterized by
      the destruction of insulin-producing beta cells in the pancreatic islets. The
      migration of T cells from blood vessels into pancreas is critical for the
      development of islet inflammation and beta cell destruction in T1D. To define the
      roles of C-C chemokine receptor type 7 (CCR7) in recruitment of T cells into
      islets, we used laser capture microdissection to isolate tissue from inflamed
      islets of nonobese diabetic (NOD) mice and uninflamed islets of BALB/c and young
      NOD mice. RT-PCR analyses detected mRNAs for CCR7 and its chemokine ligands CCL19
      (ELC; MIP-3beta) and CCL21 (SLC) in captures from inflamed, but not from
      uninflamed, islets. Immunohistology studies revealed that high endothelial
      venules in inflamed islets co-express CCL21 protein and MAdCAM-1 (an adhesion
      molecule that recruits lymphocytes into islets). Desensitization of lymphocyte
      CCR7 blocked about 75 % of T cell migration from the bloodstream into inflamed
      islets, but had no effect on B cell migration into islets. These results indicate
      that CCR7 and its ligands are important in the recruitment of T cells into
      inflamed islets and thus in the pathogenesis of T1D.

PMID- 24687733
TI  - Grammatical constraints on phonological encoding in speech production.
AB  - To better understand the influence of grammatical encoding on the retrieval and
      encoding of phonological word-form information during speech production, we
      examine how grammatical class constraints influence the activation of
      phonological neighbors (words phonologically related to the target--e.g., MOON,
      TWO for target TUNE). Specifically, we compare how neighbors that share a
      target's grammatical category (here, nouns) influence its planning and retrieval,
      assessed by picture naming latencies, and phonetic encoding, assessed by word
      productions in picture names, when grammatical constraints are strong (in
      sentence contexts) versus weak (bare naming). Within-category (noun) neighbors
      influenced planning time and phonetic encoding more strongly in sentence
      contexts. This suggests that grammatical encoding constrains phonological
      processing; the influence of phonological neighbors is grammatically dependent.
      Moreover, effects on planning times could not fully account for phonetic effects,
      suggesting that phonological interaction affects articulation after speech onset.
      These results support production theories integrating grammatical, phonological,
      and phonetic processes.

PMID- 24687734
TI  - Active maintenance of semantic representations.
AB  - In research on verbal working memory, articulatory rehearsal, a maintenance
      mechanism for phonological representations, has undergone intensive and excellent
      study. Possible mechanisms for semantic representation have received less
      attention. However, several studies have reported a double dissociation in types
      of memory deficits (semantic memory difficulties vs. phonological memory
      difficulties). This suggests the separability of two maintenance mechanisms. The
      present study focused on this separability in individuals with normal memory
      abilities, using a dual-task interference paradigm. The results indicate a
      crossover interaction between memory and interference task effects: Preventing
      articulatory rehearsal more strongly disrupted the phonological memory task,
      whereas performing a tapping task that interfered with attentional control more
      strongly disrupted semantic memory. These results suggest that semantic
      representations are actively maintained by a mechanism other than phonological
      maintenance. 

PMID- 24687735
TI  - Less means more for pigeons but not always.
AB  - When humans are asked to judge the value of a set of objects of excellent
      quality, they often give this set higher value than those same objects with the
      addition of some of lesser quality. This is an example of the affect heuristic,
      often referred to as the less-is-more effect. Monkeys and dogs, too, have shown
      this suboptimal effect. But in the present experiments, normally hungry pigeons
      chose optimally: a preferred food plus a less-preferred food over a more
      preferred food alone. In Experiment 2, however, pigeons on a less-restricted diet
      showed the suboptimal less-is-more effect. Choice on control trials indicated
      that the effect did not result from the novelty of two food items versus one. The
      effect in the less-food-restricted pigeons appears to result from the devaluation
      of the combination of the food items by the presence of the less-preferred food
      item. The reversal of the effect under greater food restriction may occur
      because, as motivation increases, the value of the less-preferred food increases
      faster than the value of the more-preferred food, thus decreasing the difference
      in value between the two foods.

PMID- 24687736
TI  - Comparative evaluation of antiproliferative effects of Brazilian green propolis,
      its main source Baccharis dracunculifolia, and their major constituents
      artepillin C and baccharin.
AB  - This study evaluated the antiproliferative activity of the Brazilian green
      propolis and Baccharis dracunculifolia extracts and their major compounds
      artepillin C and baccharin in different tumor cell lines. The lowest IC50 values
      observed for Brazilian green propolis and B. dracunculifolia extracts were 41.0
      +/- 4.5 ug/mL for U343 and 44.9 +/- 7.1 ug/mL for HepG2, respectively. Regarding
      artepillin C and baccharin, the lowest IC50 values were 20.1 +/- 2.9 for U343 and
      13.0 +/- 1.5 ug/mL for B16F10, respectively. For the association of artepillin C
      plus baccharin, the lowest IC50 result was 35.2 +/- 0.5 ug/mL for B16F10.
      Artepillin C and baccharin were more cytotoxic than both Brazilian green propolis
      and B. dracunculifolia extracts. No additive or synergistic effect was observed
      for the association of artepillin C plus baccharin. 

PMID- 24687737
TI  - Metabolism of chamaechromone in vitro with human liver microsomes and recombinant
      human drug-metabolizing enzymes.
AB  - Chamaechromone is a major component in the dried roots of Stellera chamaejasme
      with antihepatitis B virus and insecticidal activity. In this study, metabolic
      profiles of chamaechromone were investigated in human liver microsomes. One
      monohydroxide and two monoglucuronides of chamaechromone were identified. The
      enzyme kinetics for both hydroxylation and glucuronidation were fitted to the
      Michaelis-Menten equation. The hydroxylation of chamaechromone was inhibited by
      alpha-naphthoflavone, and predominantly catalyzed by recombinant human cytochrome
      P450 1A2, whereas the glucuronidation was inhibited by quercetin, 1-naphthol, and
      fluconazole, and mainly catalyzed by recombinant human UDP
      glucuronosyltransferase 1A3, 1A7, 1A9, and 2B7. 

PMID- 24687738
TI  - Antimycobacterial furofuran lignans from the roots of Anemopsis californica.
AB  - Topical preparations of Anemopsis californica have been used by Native American
      tribes in the southwestern United States and northern Mexico to treat
      inflammation and infections. We report results of bioassay-guided isolation
      conducted on a sample of A. californica roots. The furofuran lignans sesamin (1)
      and asarinin (2) were isolated and shown to have MIC values ranging from 23 to
      395 uM against five different species of environmental nontuberculous
      mycobacteria. These findings are significant given that these bacteria can cause
      skin, pulmonary, and lymphatic infections. Crude A. californica extracts were
      analyzed by liquid chromatography-mass spectrometry, and it was determined that
      sesamin and asarinin were extracted at relatively high levels from the roots (1.7
      3.1 g/kg and 1.1-1.7 g/kg, respectively), but at lower levels from the leaves
      (0.13 g/kg for both compounds). Our findings suggest that the majority of
      activity of crude A. californica root extracts against nontuberculous
      mycobacteria can be attributed to the presence of sesamin and asarinin. This
      paper is the first to report the isolation of these compounds from a member of
      the Saururaceae family, and the first to describe their activity against
      nontuberculous mycobacteria. 

PMID- 24687739
TI  - Lipase inhibition and antiobesity effect of Atractylodes lancea.
AB  - The ethanol extract of Atractylodes lancea rhizome displayed significant lipase
      inhibition with an IC50 value of 9.06 ug/mL in a human pancreatic lipase assay
      from high-throughput screening. Bioassay-guided isolation led to the
      identification of one new polyacetylene, syn-(5E,11E)-3-acetoxy-4-O-(3
      methylbutanoyl)-1,5,11-tridecatriene-7,9-diyne-3,4-diol (7), along with six known
      compounds (1-6). The structure of compound 7 was determined based on the analysis
      of NMR and MS data. Among these seven lipase inhibitors, the major compound
      atractylodin (1) showed the highest lipase inhibitory activity (IC50 = 39.12 uM).
      The antiobesity effect of the ethanol extract of Atractylodes lancea rhizome was
      evaluated in a high-fat diet-induced obesity mice model at daily dosages of 250
      mg/kg and 500 mg/kg body weight for 4 weeks, and treatment with this extract
      demonstrated a moderate efficacy at the 500 mg/kg dose level. 

PMID- 24687740
TI  - Chemical and pharmacological investigation of the stem bark of Synadenium
      grantii.
AB  - Based on the fact that Synadenium grantii is used in folk medicine for the
      treatment of peptic ulcers and inflammatory diseases, this work describes its
      chemical and pharmacological properties. Pharmacological investigation of the
      crude bark extract showed a high antioxidant activity over several scavenger
      systems, such as 2,2'-azino-bis (3-ethylenebenzothiazoline-6-sulfonic acid)* +, 1
      diphenyl-2-picrylhydrazyl*, O2 * - , and HOCl, as well as an enzymatic system
      with human myeloperoxidase and an ex vivo hemolysis system. Furthermore, the oral
      administration of the crude bark extract was able to reduce carrageenan-induced
      rat paw edema as effectively as ibuprofen. These biological activities may be
      associated with the presence of flavonoids and terpenes, as revealed by HPLC and
      NMR analyses of the crude stem bark extract. The phytochemical investigations in
      this study resulted in the isolation of friedelin and 3beta-friedelinol for the
      first time, while euphol and lanosterol were also isolated. 

PMID- 24687741
TI  - Isolation and immunosuppressive effects of 6"-O-acetylginsenoside Rb1 extracted
      from North American ginseng.
AB  - Extraction of medicinally active components from natural health products has
      become an emerging source for drug discovery. Of particular interest for this
      work was the finding and testing of a new ginsenoside from North American ginseng
      (Panax quinquefolius). In the present study, a large amount of 6"-O
      acetylginsenoside Rb1, compound 7, was found using ultrasonic extraction of North
      American ginseng with DMSO aqueous solution. This new ginsenoside was well
      identified with MS, FTIR, and 1D (1H and 13C) and 2D (gCOSY, gHSQC, and gHMBC)
      NMR. Subsequent bioassay experiments confirmed that compound 7 demonstrated an
      additional immunosuppressive activity towards inhibiting the production of nitric
      oxide and tumor necrosis factor alpha in lipopolysaccharide-induced macrophage
      cells in a dose-dependent manner using murine macrophages. This new ginsenoside
      is encouraging for the further exploration and development of novel drugs. 

PMID- 24687742
TI  - Synergistic antitumor effect of a combination of paclitaxel and carboplatin with
      nobiletin from Citrus depressa on non-small-cell lung cancer cell lines.
AB  - Non-small-cell lung carcinomas do not sufficiently respond to cancer
      chemotherapeutic drugs. Combination effects of cancer chemotherapy drugs
      (paclitaxel and carboplatin) with nobiletin or powdered Shiikuwasha extract from
      Citrus depressa were examined by isobologram and combination index analyses. It
      was demonstrated that the combination generated a synergistic inhibitory effect
      against the proliferation of the human non-small-cell lung carcinoma cell lines
      A549 and H460 and that of the two chemotherapy drugs, paclitaxel was responsible
      for this synergistic effect. Furthermore, the percentage of apoptotic cells was
      decreased with increasing rates of nobiletin to paclitaxel and carboplatin. These
      findings were considered to be attributed to the ability of nobiletin to regulate
      cells in the G1 phase, which escaped cell death initiated by paclitaxel and
      carboplatin. An antitumor activity assay showed that this combination
      significantly suppressed the growth of subcutaneous A549 tumor xenografts in nude
      mice. 

PMID- 24687743
TI  - Xanthone glycosides from Swertia bimaculata with alpha-glucosidase inhibitory
      activity.
AB  - Seven new xanthone glycosides (1-7) were isolated from the n-butanol extract of
      Swertia bimaculata, together with six known compounds (8-13). Their structures
      were elucidated on the basis of extensive spectroscopic analyses (1D- and 2D-NMR,
      HRESIMS, UV, and IR) and comparison with data reported in the literature. All the
      compounds were evaluated for their alpha-glucosidase inhibitory activities in
      vitro, and compounds 3, 4, and 7 exhibited significant activities to inhibit
      alpha-glucosidase. Meanwhile the effects of different substitutions on the alpha
      glucosidase inhibitory activity of xanthone glycosides from S. bimaculata are
      also discussed. 

PMID- 24687744
TI  - In vivo formation and bioavailability of isothiocyanates from glucosinolates in
      broccoli as affected by processing conditions.
AB  - SCOPE: To study the effect of residual myrosinase (MYR) activity in differently
      processed broccoli on sulforaphane (SR) and iberin (IB) formation,
      bioavailability, and excretion in human volunteers. METHODS AND RESULTS: Five
      different broccoli products were obtained with similar glucoraphanin (GR) and
      glucoiberin (GI) content, yet different MYR activity. Excretion of SR and IB
      conjugates in urine were determined in 15 participants after ingestion of the
      broccoli products. A reduction of 80% of MYR in the product did not cause
      differences in the total amount of SR and IB found in urine compared to the
      product with 100% MYR. Complete inactivation of MYR gave the lowest total amount
      of SR and IB in urine (10 and 19%). A residual MYR of only 2% in the product gave
      an intermediate amount (17 and 29%). The excretion half-lives of SR and IB
      conjugates were comparable for all the products (2.5 h on average), although the
      maximum excretion peak times were clearly shorter when the residual MYR was
      higher (2.3-6.1 h). CONCLUSION: For the first time, the effect of residual MYR
      activity on isothiocyanate bioavailability was systematically and quantitatively
      studied. Processing conditions have a large effect on the kinetics and
      bioavailability of isothiocyanates from broccoli.

PMID- 24687745
TI  - Response to: improving postpartum screening rates.

PMID- 24687746
TI  - Histogram analysis of apparent diffusion coefficient for the assessment of local
      aggressiveness of cervical cancer.
AB  - PURPOSE: To retrospectively explore the value of apparent diffusion coefficient
      (ADC) histogram in assessing local aggressiveness of cervical cancer. METHODS: 53
      patients with cervical cancer, including 7 cases at stage IB1, 17 cases at stage
      IB2 and 29 cases at stage IIA, were subjected to preoperative MRI including
      diffusion-weighted imaging with b values of 0 and 800 s/mm(2). The average of
      mean ADC values (ADCmean), minimum ADC values (ADCmin) and the 5th to 85th
      percentile ADC values every 10 % (ADC5 %, ADC15 %, ADC85 %) were measured. ADC
      values were compared between subgroups according to pathologic subtype,
      histological differentiation, depth of cervical infiltration, and lymph node
      metastases. RESULTS: ADCmean and ADCmin for adenocarcinoma were 1,170.3 +/- 97.8
      * 10(-6) and 748.7 +/- 157.5 * 10(-6) mm(2) s(-1), respectively, significantly
      higher than that of squamous cell carcinoma (SCC) (1,053.8 +/- 134.3 * 10(-6) and
      615.6 +/- 170.2 * 10(-6) mm(2) s(-1), respectively). ADCmean and ADC5 %-ADC85 %
      of well or moderately tumor were significantly higher than poorly differentiated
      tumor, but ADCmin was not significantly different among different differentiated
      cervical cancer. Only ADC5 %-ADC45 % could discriminate well or moderately
      differentiated SCC from poorly differentiated SCC. ADC5 % for distinguishing
      well/moderately from poorly differentiated cervical cancer had a largest AUC
      (0.83). There was no statistical difference in ADC value for different depth of
      cervical infiltration or lymph node metastases. CONCLUSIONS: ADC values are
      helpful in assessing pathologic subtype and the differentiation of cervical
      cancer.

PMID- 24687747
TI  - The impacts of different long-term fertilization regimes on the bioavailability
      of arsenic in soil: integrating chemical approach with Escherichia coli
      arsRp::luc-based biosensor.
AB  - An Escherichia coli arsRp::luc-based biosensor was constructed to measure the
      bioavailability of arsenic (As) in soil. In previous induction experiments, it
      produced a linear response (R (2) = 0.96, P < 0.01) to As from 0.05 to 5 MUmol/L
      after a 2-h incubation. Then, both chemical sequential extraction, Community
      Bureau of Reference recommended sequential extraction procedures (BCR-SEPs) and
      E. coli biosensor, were employed to assess the impact of different long-term
      fertilization regimes containing N, NP, NPK, M (manure), and NPK + M treatments
      on the bioavailability of arsenic (As) in soil. Per the BCR-SEPs analysis, the
      application of M and M + NPK led to a significant (P < 0.01) increase of
      exchangeable As (2-7 times and 2-5 times, respectively) and reducible As (1.5-2.5
      times and 1.5-2.3 times, respectively) compared with the no fertilization treated
      soil (CK). In addition, direct contact assay of E. coli biosensor with soil
      particles also supported that bioavailable As in manure-fertilized (M and M +
      NPK) soil was significantly higher (P < 0.01) than that in CK soil (7 and 9
      times, respectively). Organic carbon may be the major factor governing the
      increase of bioavailable As. More significantly, E. coli biosensor-determined As
      was only 18.46-85.17 % of exchangeable As and 20.68-90.1 % of reducible As based
      on BCR-SEPs. In conclusion, NKP fertilization was recommended as a more suitable
      regime in As-polluted soil especially with high As concentration, and this E.
      coli arsRp::luc-based biosensor was a more realistic approach in assessing the
      bioavailability of As in soil since it would not overrate the risk of As to the
      environment. 

PMID- 24687748
TI  - Glucose kinases from Streptomyces peucetius var. caesius.
AB  - Glucose kinases (Glks) are enzymes of the glycolytic pathway involved in glucose
      phosphorylation. These enzymes can use various phosphoryl donors such as ATP,
      ADP, and polyphosphate. In several streptomycetes, ATP-glucose kinase (ATP-Glk)
      has been widely studied and regarded as the main glucose phosphorylating enzyme
      and is likely a regulatory protein in carbon catabolite repression. In cell
      extracts from the doxorubicin overproducing strain Streptomyces peucetius var.
      caesius, grown in glucose, a polyphosphate-dependent Glk (Pp-Glk) was detected by
      zymogram. Maximum activity was observed during the stationary growth phase (48 h)
      of cells grown in 100 mM glucose. No activity was detected when 20 mM glutamate
      was used as the only carbon source, supporting a role for glucose in inducing
      this enzyme. Contrary to wild-type strains of Streptomyces coelicolor,
      Streptomyces lividans, and Streptomyces thermocarboxydus K-155, S. peucetius var.
      caesius produced 1.8 times more Pp-Glk than ATP-Glk. In addition, this
      microorganism produced five and four times more Pp-Glk and anthracyclines,
      respectively, than its wild-type S. peucetius parent strain, supporting a role
      for this enzyme in antibiotic production in the overproducer strain. A cloned 726
      bp DNA fragment from S. peucetius var. caesius encoded a putative Pp-Glk, with
      amino acid identities between 83 and 87 % to orthologous sequences from the above
      cited streptomycetes. The cloned fragment showed the polyphosphate-binding
      sequences GXDIGGXXIK, TXGTGIGSA, and KEX(4)SWXXWA. Sequences for the Zn-binding
      motif were not detected in this fragment, suggesting that Pp-Glk is not related
      to the Glk ROK family of proteins. 

PMID- 24687749
TI  - Role of surface residue 184 in the catalytic activity of NADH oxidase from
      Streptococcus pyogenes.
AB  - Nicotinamide adenine dinucleotide (NADH) oxidase from Streptococcus pyogenes
      (SpNox) is a flavoprotein harboring one molecule of noncovalently bound flavin
      adenine dinucleotide. It catalyzes the oxidation of NADH by reducing molecular O2
      to H2O directly through a four-electron reduction. In this study, we selected the
      lysine residues on the surface of SpNox and mutated them into arginine residues
      to study the effect on the enzyme activity. A single-point mutation (K184R) at
      the surface of SpNox enhanced NADH oxidase activity by approximately 50 % and
      improved thermostability with 46.6 % longer half life at 30  degrees C. Further
      insights into the function of residue K184 were obtained by substituting it with
      other nonpolar, polar, positively charged, and negatively charged residues. To
      elucidate the role of this residue, computer-assisted molecular modeling and
      substrate docking were performed. The results demonstrate that even a single
      mutation at the surface of the enzyme induces changes in the interaction at the
      active site and affects the activity and stability. Additionally, the data also
      suggest that the K184R mutant can be used as an effective biocatalyst for NAD(+)
      regeneration in L-rare sugar production. 

PMID- 24687750
TI  - High-cell-density cultivation of recombinant Escherichia coli, purification and
      characterization of a self-sufficient biosynthetic octane omega-hydroxylase.
AB  - We have recently described the biocatalytic characterization of a self-sufficent
      biosynthetic alkane hydroxylase based on CYP153A13a from Alcanivorax borkumensis
      SK2 (thereafter A13-Red). Despite remarkable regio- and chemo-selectivity, A13
      Red suffers of a difficult-to-reproduce expression and moderate operational
      stability. In this study, we focused our efforts on the production of A13-Red
      using high-cell-density cultivation (HCDC) of recombinant Escherichia coli. We
      achieved 455 mg (5,000 nmol) of functional enzyme per liter of culture. Tight
      control of cultivation parameters rendered the whole process highly reproducible
      compared with flask cultivations. We optimized the purification of the
      biocatalyst that can be performed in either two or three steps depending on the
      application needed to afford A13-Red up to 95 % homogeneous. We investigated
      different reaction conditions and found that the total turnover numbers of A13
      Red during the in vitro hydroxylation of n-octane could reach up to 3,250 to
      produce 1-octanol (1.6 mM) over a period of 78 h.

PMID- 24687751
TI  - Evaluation of MALDI-TOF mass spectrometry for identification of environmental
      yeasts and development of supplementary database.
AB  - Yeast identification using traditional methods which employ morphological,
      physiological, and biochemical characteristics can be considered a hard task as
      it requires experienced microbiologists and a rigorous control in culture
      conditions that could implicate in different outcomes. Considering clinical or
      industrial applications, the fast and accurate identification of microorganisms
      is a crescent demand. Hence, molecular biology approaches has been extensively
      used and, more recently, protein profiling using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has proved
      to be an even more efficient tool for taxonomic purposes. Nonetheless, concerning
      to mass spectrometry, data available for the differentiation of yeast species for
      industrial purpose is limited and reference databases commercially available
      comprise almost exclusively clinical microorganisms. In this context, studies
      focusing on environmental isolates are required to extend the existing databases.
      The development of a supplementary database and the assessment of a commercial
      database for taxonomic identifications of environmental yeast are the aims of
      this study. We challenge MALDI-TOF MS to create protein profiles for 845 yeast
      strains isolated from grape must and 67.7 % of the strains were successfully
      identified according to previously available manufacturer database. The remaining
      32.3 % strains were not identified due to the absence of a reference spectrum.
      After matching the correct taxon for these strains by using molecular biology
      approaches, the spectra concerning the missing species were added in a
      supplementary database. This new library was able to accurately predict
      unidentified species at first instance by MALDI-TOF MS, proving it is a powerful
      tool for the identification of environmental yeasts.

PMID- 24687752
TI  - Extraction of copper from an oxidized (lateritic) ore using bacterially catalysed
      reductive dissolution.
AB  - An oxidized lateritic ore which contained 0.8 % (by weight) copper was bioleached
      in pH- and temperature-controlled stirred reactors under acidic reducing
      conditions using pure and mixed cultures of the acidophilic chemolithotrophic
      bacterium Acidithiobacillus ferrooxidans. Sulfur was provided as the electron
      donor for the bacteria, and ferric iron present in goethite (the major ferric
      iron mineral present in the ore) acted as electron acceptor. Significantly more
      copper was leached by bacterially catalysed reductive dissolution of the laterite
      than in aerobic cultures or in sterile anoxic reactors, with up to 78 % of the
      copper present in the ore being extracted. This included copper that was leached
      from acid-labile minerals (chiefly copper silicates) and that which was
      associated with ferric iron minerals in the lateritic ore. In the anaerobic
      bioreactors, soluble iron in the leach liquors was present as iron (II) and
      copper as copper (I), but both metals were rapidly oxidized (to iron (III) and
      copper (II)) when the reactors were aerated. The number of bacteria added to the
      reactors had a critical role in dictating the rate and yield of copper
      solubilised from the ore. This work has provided further evidence that reductive
      bioprocessing, a recently described approach for extracting base metals from
      oxidized deposits, has the potential to greatly extend the range of metal ores
      that can be biomined.

PMID- 24687753
TI  - Cerato-platanins: a fungal protein family with intriguing properties and
      application potential.
AB  - Cerato-platanin proteins are small, secreted proteins with four conserved
      cysteines that are abundantly produced by filamentous fungi with all types of
      lifestyles. These proteins appear to be readily recognized by other organisms and
      are therefore important factors in interactions of fungi with other organisms,
      e.g. by stimulating the induction of defence responses in plants. However, it is
      not known yet whether the main function of cerato-platanin proteins is associated
      with these fungal interactions or rather a role in fungal growth and development.
      Cerato-platanin proteins seem to unify several biochemical properties that are
      not found in this combination in other proteins. On one hand, cerato-platanins
      are carbohydrate-binding proteins and are able to bind to chitin and N
      acetylglucosamine oligosaccharides; on the other hand, they are able to self
      assemble at hydrophobic/hydrophilic interfaces and form protein layers, e.g. on
      the surface of aqueous solutions, thereby altering the polarity of solutions and
      surfaces. The latter property is reminiscent of hydrophobins, which are also
      small, secreted fungal proteins, but interestingly, the surface-activity-altering
      properties of cerato-platanins are the opposite of what can be observed for
      hydrophobins. The so far known biochemical properties of cerato-platanin proteins
      are summarized in this review, and potential biotechnological applications as
      well as implications of these properties for the biological functions of cerato
      platanin proteins are discussed. 

PMID- 24687754
TI  - Metabolic engineering for the microbial production of carotenoids and related
      products with a focus on the rare C50 carotenoids.
AB  - Carotenoids, a subfamily of terpenoids, are yellow- to red-colored pigments
      synthesized by plants, fungi, algae, and bacteria. They are ubiquitous in nature
      and take over crucial roles in many biological processes as for example
      photosynthesis, vision, and the quenching of free radicals and singlet oxygen.
      Due to their color and their potential beneficial effects on human health,
      carotenoids receive increasing attention. Carotenoids can be classified due to
      the length of their carbon backbone. Most carotenoids have a C40 backbone, but
      also C30 and C50 carotenoids are known. All carotenoids are derived from
      isopentenyl pyrophosphate (IPP) as a common precursor. Pathways leading to IPP as
      well as metabolic engineering of IPP synthesis and C40 carotenoid production have
      been reviewed expertly elsewhere. Since C50 carotenoids are synthesized from the
      C40 carotenoid lycopene, we will summarize common strategies for optimizing
      lycopene production and we will focus our review on the characteristics,
      biosynthesis, glycosylation, and overproduction of C50 carotenoids.

PMID- 24687755
TI  - Influence of intrapartum antibiotic prophylaxis against group B Streptococcus on
      the early newborn gut composition and evaluation of the anti-Streptococcus
      activity of Bifidobacterium strains.
AB  - Several factors are known to influence the early colonization of the gut in
      newborns. Among them, the use of antibiotics on the mother during labor, referred
      to as intrapartum antibiotic prophylaxis (IAP), has scarcely been investigated,
      although this practice is routinely used in group B Streptococcus (GBS)-positive
      women. This work is therefore aimed at verifying whether IAP can influence the
      main microbial groups of the newborn gut microbiota at an early stage of
      microbial establishment. Fifty-two newborns were recruited: 26 born by mothers
      negative to GBS (control group) and 26 by mothers positive to GBS and subjected
      to IAP with ampicillin (IAP group). Selected microbial groups (Lactobacillus
      spp., Bidobacterium spp., Bacteroides fragilis, Clostridium difficile, and
      Escherichia coli) were quantified with real-time PCR on DNA extracted from
      newborn feces. Further analysis was performed within the Bidobacterium genus by
      using DGGE after amplification with genus-specific primers. Results obtained
      showed a significant decrease of the bifidobacteria counts after antibiotic
      treatment of the mother. Bifidobacteria were found to be affected by IAP not only
      quantitatively but also qualitatively. In fact, IAP determined a decrement in the
      frequency of Bidobacterium breve, Bidobacterium bifidum, and Bidobacterium
      dentium with respect to the control group. Moreover, this study has preliminarily
      evaluated that some bifidobacterial strains, previously selected for use in
      infants, have antibacterial properties against GBS and are therefore potential
      candidates for being applied as probiotics for the prevention of GBS infections. 

PMID- 24687757
TI  - A fast and sensitive method for the simultaneous identification of three
      important nematode species of the genus Ditylenchus.
AB  - BACKGROUND: Nematodes of the genus Ditylenchus are parasites of a wide range of
      hosts, including higher plants. The most destructive of these species are D.
      dipsaci and D. destructor, two frequently quarantined pests. No rapid molecular
      method is available for unambiguous detection and distinguishing of these species
      from each other or from D. gigas, a pest of Vicia faba, either by multiplex PCR
      or real-time PCR. RESULTS: By aligning all D. dipsaci, D. destructor and D. gigas
      rDNA sequences, the authors found a constant-sequence region that could be used
      as a universal 5' primer and constant regions in the ITS1 regions of the rDNAs
      that could be used as species-specific 3' primers for PCR detection of these
      nematodes. A standardised protocol was developed for both singleplex- and triplex
      mode PCR that yields a single product of distinct length for each of the species.
      The PCR protocol has also been adapted for real-time PCR. CONCLUSION: The present
      diagnostic PCR protocol is the only method that can identify all three species
      with the use of a triplex and/or a singleplex PCR assay. Importantly, the 3'
      primer for D. destructor ITS1 rDNA was designed so that it would hybridise all
      haplotypes.

PMID- 24687756
TI  - Glycine N-methyltransferase expression in the hippocampus and its role in
      neurogenesis and cognitive performance.
AB  - The hippocampus is a brain area characterized by its high plasticity, observed at
      all levels of organization: molecular, synaptic, and cellular, the latter
      referring to the capacity of neural precursors within the hippocampus to give
      rise to new neurons throughout life. Recent findings suggest that promoter
      methylation is a plastic process subjected to regulation, and this plasticity
      seems to be particularly important for hippocampal neurogenesis. We have detected
      the enzyme GNMT (a liver metabolic enzyme) in the hippocampus. GNMT regulates
      intracellular levels of SAMe, which is a universal methyl donor implied in almost
      all methylation reactions and, thus, of prime importance for DNA methylation. In
      addition, we show that deficiency of this enzyme in mice (Gnmt-/-) results in
      high SAMe levels within the hippocampus, reduced neurogenic capacity, and spatial
      learning and memory impairment. In vitro, SAMe inhibited neural precursor cell
      division in a concentration-dependent manner, but only when proliferation signals
      were triggered by bFGF. Indeed, SAMe inhibited the bFGF-stimulated MAP kinase
      signaling cascade, resulting in decreased cyclin E expression. These results
      suggest that alterations in the concentration of SAMe impair neurogenesis and
      contribute to cognitive decline.

PMID- 24687758
TI  - Distribution and quantitative detection of GABAA receptor in Carassius auratus
      gibelio.
AB  - Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in brain, is
      synthesized from glutamate and metabolized to succinic semialdehyde by glutamic
      acid decarboxylase (GAD) and GABA transaminase (GABA-T), respectively. The fast
      inhibitory effect of GABA is mediated by GABA type A (GABAA) receptors that are
      associated with several neurological disorders, and GABAA receptors are targets
      of several therapeutic agents. To date, information on the distribution and
      quantity of GABAA receptors in Carassius auratus gibelio is still limited. We
      investigated for the first time, the tissue-specific distribution of GABAARbeta2a
      and GABAARbeta2b, the two subunits of the predominant GABAA receptor subtype
      (alpha1beta2gamma2), and then, the expression of GABAARbeta2a, GABAARbeta2b, GAD,
      and quantified GABA-T genes in different tissues by quantitative real-time PCR
      method and compared different expressions between two developmental stages of C.
      auratus gibelio. Results showed that GABAARbeta2a and GABAARbeta2b genes
      expressed in both brain and peripheral organs using reverse transcription
      polymerase chain reaction. In addition, the majority of GABAARbeta2a,
      GABAARbeta2b, GAD, and GABA-T were mainly synthesized in brain; however, a
      considerable amount of GABA-T was secreted from the peripheral tissues,
      especially in the liver. Moreover, the expression of GABAARbeta2a and
      GABAARbeta2b genes in different tissues varied with body weight change. This
      study provides a reference for further studies on GABA and GABAA receptors
      subunits and an insight on the possible pharmacological properties of the GABAA
      receptor in C. auratus gibelio. 

PMID- 24687759
TI  - Molecular cytogenetic identification of B genome chromosomes linked to blackleg
      disease resistance in Brassica napus * B. carinata interspecific hybrids.
AB  - KEY MESSAGE: Provide evidence that the Brassica B genome chromosome B3 carries
      blackleg resistance gene, and also the B genome chromosomes were inherited
      several generations along with B. napus chromosomes. Blackleg disease caused by
      fungus Leptosphaeria maculans causes significant yield losses in Brassica napus.
      Brassica carinata possesses excellent resistance to this disease. To introgress
      blackleg resistance, crosses between B. napus cv. Westar and B. carinata were
      done. The interspecific-hybrids were backcrossed twice to Westar and self
      pollinated three times to produce BC2S3 families. Doubled haploid lines (DH1)
      were produced from one blackleg resistant family. SSR markers were used to study
      the association between B genome chromosome(s) and blackleg resistance. The
      entire B3 chromosome of B. carinata was associated with blackleg resistance in
      DH1. A second DH population (DH2) was produced from F1s of resistant DH1 lines
      crossed to blackleg susceptible B. napus cv. Polo where resistance was found to
      be associated with SSR markers from the middle to bottom of the B3 and top of the
      B8 chromosomes. The results demonstrated that the B3 chromosome carried gene(s)
      for blackleg resistance. Genomic in situ hybridization (GISH) and GISH-like
      analysis of the DH2 lines revealed that susceptible lines, in addition to B.
      napus chromosomes, possessed one pair of B genome chromosomes (2n = 40), while
      resistant lines had either one (2n = 40) or two pairs (2n = 42) of B chromosomes.
      The molecular and GISH data suggested that the B chromosome in the susceptible
      lines was B7, while it was difficult to confirm the identity of the B chromosomes
      in the resistant lines. Also, B chromosomes were found to be inherited over
      several generations along with B. napus chromosomes.

PMID- 24687760
TI  - Safety of postoperative thromboprophylaxis after major hepatobiliary-pancreatic
      surgery in Japanese patients.
AB  - BACKGROUND AND PURPOSE: Thromboprophylaxis is recommended for preventing
      postoperative venous thromboembolism (VTE) after abdominal surgery; however, its
      use after major hepatobiliary-pancreatic surgery is typically avoided as it
      increases the risk of bleeding. We conducted this study to evaluate the safety of
      thromboprophylaxis after major hepatobiliary-pancreatic surgery. METHODS: We
      analyzed the rates of postoperative bleeding, VTE, morbidity, and prolonged
      hospital stay in 349 patients who underwent major hepatobiliary-pancreatic
      surgery, such as pancreaticoduodenectomy, hemihepatectomy or greater, and
      hepatopancreaticoduodenectomy. RESULTS: Chemical thromboprophylaxis was
      associated with significantly increased rates and risks of overall bleeding
      events vs. no chemical thromboprophylaxis (26.6 vs. 8.5%, respectively). The rate
      of minor hemorrhage was significantly higher in patients who received chemical
      thromboprophylaxis (21.7 vs. 3.5%); however, there were no differences in the
      rate of major hemorrhage requiring blood transfusion or hemostatic intervention
      between the groups (4.8 vs. 4.9%). The postoperative VTE rate was also
      significantly decreased by chemical thromboprophylaxis (2.9 vs. 7.7%). However,
      chemical thromboprophylaxis did not affect the rate of SSI, severe morbidity, or
      duration of the postoperative hospital stay. CONCLUSION: We consider that
      chemical thromboprophylaxis is beneficial and can be safely used even after major
      hepatobiliary-pancreatic surgery.

PMID- 24687763
TI  - Bullying: what speech-language pathologists should know.
AB  - PURPOSE: The purpose of this tutorial is to introduce speech-language
      pathologists (SLPs) to the broad issues surrounding the problem of school
      bullying in childhood and adolescence. Specifically, types of bullying and their
      causes are considered, as are the roles students take when bullying occurs and
      the effects of bullying on students with communication disorders. Strategies and
      suggestions to help SLPs more effectively prevent and manage bullying of students
      with communication disorders are discussed. METHOD: A review of the scholarly
      literature in education, psychology, child and adolescent development, and speech
      language pathology was conducted. Recommendations for how SLPs can prevent and
      intervene in bullying incidences were extrapolated from the reviewed literature.
      RESULTS: Students with communication disorders are at particularly high risk for
      being bullied by peers. Some students with communication disorders are
      "provocative victims" in that they demonstrate impairments in social skills that
      draw the attention of bullies. Both provocative victims and typical students may
      react aggressively when bullied and bully others in retaliation. CONCLUSION: SLPs
      can and should help to create an inclusive environment for all students while
      addressing bullying of students with communication disorders via therapeutic
      activities.

PMID- 24687761
TI  - Effect of glucocorticoids on neuronal and vascular pathology in a transgenic
      model of selective Muller cell ablation.
AB  - Retinal diseases such as macular telangiectasis type 2 (MacTel), age-related
      macular degeneration (AMD) and diabetic retinopathy (DR) affect both neurons and
      blood vessels. Treatments addressing both at the same time might have advantages
      over more specific approaches, such as vascular endothelial growth factor (VEGF)
      inhibitors, which are used to treat vascular leak but are suspected to have a
      neurotoxic effect. Here, we studied the effects of an intravitreal injection of
      triamcinolone acetonide (TA) in a transgenic model in which patchy Muller cell
      ablation leads to photoreceptor degeneration, vascular leak, and intraretinal
      neovascularization. TA was injected 4 days before Muller cell ablation. Changes
      in photoreceptors, microglia and Muller cells, retinal vasculature, differential
      expression of p75 neurotrophin receptor (p75(NTR) ), tumor necrosis factor-alpha
      (TNFalpha), the precursor and mature forms of neurotrophin 3 (pro-NT3 and mature
      NT3) and activation of the p53 and p38 stress-activated protein kinase (p38/SAPK)
      signaling pathways were examined. We found that TA prevented photoreceptor
      degeneration and inhibited activation of microglial and Muller cells. TA
      attenuated Muller cell loss and inhibited overexpression of p75(NTR) , TNFalpha,
      pro-NT, and the activation of p53 and p38/SAPK signaling pathways. TA not only
      prevented the development of retinal vascular lesions but also inhibited
      fluorescein leakage from established vascular lesions. TA inhibited
      overexpression of VEGF in transgenic mice but without affecting its basal level
      expression in the normal retina. Our data suggest that glucocorticoid treatment
      may be beneficial for treatment of retinal diseases such as MacTel, AMD, and DR
      that affect both neurons and the vasculature.

PMID- 24687764
TI  - Modifying attitudes of Arab school teachers toward stuttering.
AB  - PURPOSE: The authors of this quasi-experimental design study explored the effect
      of an educational documentary video that presented factual and emotional aspects
      of stuttering on changing attitudes toward stuttering of preservice trainees and
      in-service public school teachers in Kuwait. METHOD: Participants were 99
      preservice trainees (48 control, 51 experimental) and 103 in-service teachers (49
      control, 54 experimental). All participants completed 22 items from the Public
      Opinion Survey of Human Attributes-Stuttering (POSHA-S; St. Louis, 2005;
      translated into Arabic) and 17 additional items pre and post treatment.
      Participants in the experimental group viewed the awareness video. RESULTS:
      Pretreatment comparisons confirmed that the control and experimental groups did
      not differ on their attitudes toward stuttering. As predicted, the posttreatment
      ratings for the control group were not different from the pretreatment ratings. A
      significant shift in attitudes (mostly in a positive direction) from pre to post
      treatment was observed for the experimental group of preservice trainees but not
      for the experimental group of in-service teachers. Interpretation of the
      difference in outcomes for the experimental preservice group as compared to the
      experimental in-service group is confounded by gender differences across groups.
      CONCLUSION: The authors of this study demonstrated that it is possible to
      positively modify preservice trainees' attitudes of people who stutter by using
      an educational documentary video.

PMID- 24687765
TI  - Phonological skills in English language learners.
AB  - PURPOSE: The purpose of this study was to examine the English phonological skills
      of English language learners (ELLs) over 5 time points. METHOD: Sound class
      accuracy, whole-word accuracy, percentage of occurrence of phonological patterns,
      and sociolinguistic correlational analyses were investigated in 19 ELLs ranging
      in age from 5;0 (years;months) to 7;6. RESULTS: Accuracy across all samples was
      over 90% for all sound classes except fricatives and increased for all sound
      classes across time. Whole-word accuracy was high and increased across time. With
      the exception of cluster reduction, stopping, and final consonant deletion, the
      frequency of occurrence for phonological patterns was less than or equal to 5% at
      every time point. Sociolinguistic variables such as age of arrival, age of
      exposure, and age were significantly related to phonological skills. CONCLUSIONS:
      The results were consistent with the hypotheses outlined in Flege's (1995) speech
      learning model in that the phonological skills of ELLs increased over time and as
      a function of age of arrival and time. Thus, speech-language pathologists (SLPs)
      also should expect phonological skills in ELLs to increase over time, as is the
      case in monolingual children. SLPs can use the longitudinal and connected-speech
      results of this study to interpret their assessments of the phonological skills
      of ELLs.

PMID- 24687766
TI  - Longitudinal analysis of receptive vocabulary growth in young Spanish English
      speaking children from migrant families.
AB  - PURPOSE: The authors of this study described developmental trajectories and
      predicted kindergarten performance of Spanish and English receptive vocabulary
      acquisition of young Latino/a English language learners (ELLs) from
      socioeconomically disadvantaged migrant families. In addition, the authors
      examined the extent to which gender and individual initial performance in Spanish
      predict receptive vocabulary performance and growth rate. METHOD: The authors
      used hierarchical linear modeling of 64 children's receptive vocabulary
      performance to generate growth trajectories, predict performance at school entry,
      and examine potential predictors of rate of growth. The timing of testing varied
      across children. The ELLs (prekindergarten to 2nd grade) participated in 2-5
      testing sessions, each 6-12 months apart. RESULTS: The ELLs' average predicted
      standard score on an English receptive vocabulary at kindergarten was nearly 2
      SDs below the mean for monolingual peers. Significant growth in the ELLs'
      receptive vocabulary was observed between preschool and 2nd grade, indicating
      that the ELLs were slowly closing the receptive vocabulary gap, although their
      average score remained below the standard score mean for age-matched monolingual
      peers. The ELLs demonstrated a significant decrease in Spanish receptive
      vocabulary standard scores over time. Initial Spanish receptive vocabulary was a
      significant predictor of growth in English receptive vocabulary. High initial
      Spanish receptive vocabulary was associated with greater growth in English
      receptive vocabulary and decelerated growth in Spanish receptive vocabulary.
      Gender was not a significant predictor of growth in either English or Spanish
      receptive vocabulary. CONCLUSION: ELLs from low socioeconomic backgrounds may be
      expected to perform lower in English compared with their monolingual English
      peers in kindergarten. Performance in Spanish at school entry may be useful in
      identifying children who require more intensive instructional support for English
      vocabulary growth. Findings substantiate the need for progress monitoring across
      the early school years.

PMID- 24687767
TI  - Effect of language context on ratings of shy and unsociable behaviors in English
      language learner children.
AB  - PURPOSE: The primary goal of this study was to explore the effect of language
      context on the socially withdrawn behaviors of school-age-children who are
      English language learners (ELLs) from middle- to high-socioeconomic status (SES)
      backgrounds. This is one of the 1st studies to address the frequently confused
      concepts of shyness and unsociability as independent constructs within the ELL
      population. The authors of this study also investigated the feasibility of an
      experimental parent and child questionnaire that examines shyness and
      unsociability across native-language and English-speaking contexts. METHOD:
      Children and mothers (34 of whom were ELLs and 37 of whom were native English
      speakers) were administered an experimental questionnaire examining the
      children's shy and unsociable behavior in native-language and English-speaking
      contexts. RESULTS: Children and mothers in the ELL group reported significantly
      higher ratings of shy behavior in English-speaking versus native-language
      contexts, whereas unsociable ratings did not differ across language contexts.
      CONCLUSIONS: Shyness and unsociability are distinguishable behaviors in ELL
      children, and researchers should consider these constructs when examining
      withdrawal. In addition, examining ELL children's behavior across language
      contexts provides a valuable method for investigating language-influenced
      behavioral problems. This study demonstrates the need for service providers to
      evaluate behavior across subtype and language context before pathologizing
      withdrawal in ELL children.

PMID- 24687768
TI  - Systematic individualized narrative language intervention on the personal
      narratives of children with autism.
AB  - PURPOSE: The purpose of this study was to investigate the effect of an
      individualized, systematic language intervention on the personal narratives of
      children with autism. METHOD: A single-subject, multiple-baseline design across
      participants and behaviors was used to examine the effect of the intervention on
      language features of personal narratives. Three 6- to 8-year-old boys with autism
      participated in 12 individual intervention sessions that targeted 2-3 story
      grammar elements (e.g., problem, plan) and 3-4 linguistic complexity elements
      (e.g., causal subordination, adverbs) selected from each participant's baseline
      performance. Intervention involved repeated retellings of customized model
      narratives and the generation of personal narratives with a systematic reduction
      of visual and verbal scaffolding. Independent personal narratives generated at
      the end of each baseline, intervention, and maintenance session were analyzed for
      presence and sophistication of targeted features. RESULTS: Graphical and
      statistical results showed immediate improvement in targeted language features as
      a function of intervention. There was mixed evidence of maintenance 2 and 7 weeks
      after intervention. CONCLUSION: Children with autism can benefit from an
      individualized, systematic intervention targeting specific narrative language
      features. Greater intensity of intervention may be needed to gain enduring
      effects for some language features.

PMID- 24687769
TI  - Anaplastic large-cell lymphoma associated with breast implants: a unique entity
      within the spectrum of peri-implant effusions.
AB  - Anaplastic large-cell lymphoma (ALCL) is a rare and newly described complication
      associated with breast implants. Patients often present with a peri-implant
      effusion, which is amenable to fine-needle aspiration. The laboratory handling of
      peri-implant effusions for cytology and ancillary studies is as crucial as
      recognizing the characteristic cytology of ALCL. All cases of peri-implant
      effusions were retrieved from the PathWest database between January 2003 and May
      2013, yielding four cases of breast implant-associated ALCL and six benign
      samples. The cytological features were evaluated and information from ancillary
      studies collated. Clinical and follow-up histology was available in all cases.
      All ALCL cases contained highly atypical lymphoid cells including 'hallmark'
      cells. In contrast, benign peri-implant effusions showed a mixture of
      inflammatory cells, being either neutrophil-rich (three cases) or lymphocyte-rich
      (three cases). A CD30 positive, ALK1 negative immunophenotype was demonstrated in
      all cases on cell block immunohistochemistry. Flow cytometry and T-cell receptor
      clonality studies confirmed aberrant T-cell immunophenotype in four of four and
      clonally rearranged T-cell receptor antigens in three of three cases. ALCL was
      identified in three of four subsequent capsulectomies. Staging confirmed disease
      limited to the capsular tissue or peri-implant effusion in all cases. None of the
      six patients with benign peri-implant effusions developed lymphoma during follow
      up. Cases of ALCL accounted for 40% of peri-implant effusions received over a 10
      year period, indicating the rarity of these samples and the high likelihood of
      malignancy. Awareness of this entity and its presentation should allow for
      appropriate triage of these specimens and definitive diagnosis on effusion
      specimens.

PMID- 24687770
TI  - Reactions of nucleophiles with nitroarenes: multifacial and versatile
      electrophiles.
AB  - In this overview, it is shown that there are many initial reactions between
      nitroarenes and nucleophiles: addition to the electron-deficient ring at
      positions occupied by halogen and hydrogen atoms, addition to the nitro group,
      single-electron transfer (SET), and other types of initial reactions. The
      resulting intermediates react further in a variety of ways to form products of
      nucleophilic substitution of a halogen atom (SN Ar), a hydrogen atom (SN ArH),
      and others. Many variants of these processes are briefly discussed, particularly
      in relation of rates of the initial reactions and further transformations. 

PMID- 24687771
TI  - Brain networks disconnection in early multiple sclerosis cognitive deficits: an
      anatomofunctional study.
AB  - Severe cognitive impairment involving multiple cognitive domains can occur early
      during the course of multiple sclerosis (MS). We investigated resting state
      functional connectivity changes in large-scale brain networks and related
      structural damage underlying cognitive dysfunction in patients with early MS.
      Patients with relapsing MS (3-5 years disease duration) were prospectively
      assigned to two groups based on a standardized neuropsychological evaluation: (1)
      cognitively impaired group (CI group, n = 15), with abnormal performances in at
      least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal
      performances in all tests. Patients and age-matched healthy controls underwent a
      multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2
      images, diffusion imaging and resting state functional MRI. Structural MRI
      analysis revealed that CI patients had a higher white matter lesion load compared
      to CP and a more severe atrophy in gray matter regions highly connected to
      networks involved in cognition. Functional connectivity measured by integration
      was increased in CP patients versus controls in attentional networks (ATT), while
      integration was decreased in CI patients compared to CP both in the default mode
      network (DMN) and ATT. An anatomofunctional study within the DMN revealed that
      functional connectivity was mostly altered between the medial prefrontal cortex
      (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and
      controls. In a multilinear regression model, functional correlation between MPFC
      and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT
      networks may deprive the brain of compensatory mechanisms required to face
      widespread structural damage.

PMID- 24687772
TI  - MicroRNAs as therapeutic targets in human cancers.
AB  - MicroRNAs (miRNAs) are evolutionarily conserved, small, regulatory RNAs that
      negatively regulate gene expression. Extensive research in the last decade has
      implicated miRNAs as master regulators of cellular processes with essential role
      in cancer initiation, progression, and metastasis, making them promising
      therapeutic tools for cancer management. In this article, we will briefly review
      the structure, biogenesis, functions, and mechanism of action of these miRNAs,
      followed by a detailed analysis of the therapeutic potential of these miRNAs. We
      will focus on the strategies presently used for miRNA therapy; discuss their use
      and drawbacks; and the challenges and future directions for the development of
      miRNA-based therapy for human cancers.

PMID- 24687774
TI  - Mulberroside A protects against ischemic impairment in primary culture of rat
      cortical neurons after oxygen-glucose deprivation followed by reperfusion.
AB  - Mulberroside A is a natural polyhydroxylated stilbene compound present at
      relatively high abundance in the roots and twigs of Morus alba L. It is known for
      its nephroprotective, hypoglycemic, and antidiabetic effects. Because its
      metabolite, oxyresveratrol, possessed purported anti-inflammatory and
      neuroprotective effects, we proposed that mulberroside A may elicit
      neuroprotective effects that can be used in the treatment of brain ischemic
      injury. Therefore, we decided to investigate the pharmacological properties of
      mulberroside A in primary culture of rat cortical neurons after oxygen-glucose
      deprivation followed by reperfusion (OGD/R), evaluating its ability to counteract
      the hypoxia-ischemia impairment. The results showed that mulberroside A elicited
      neuroprotective effects comparable to nimodipine. The mechanistic studies showed
      that mulberroside A decreased the expressions of tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-1beta, and IL-6 and inhibited the activation of NALP3,
      caspase-1, and nuclear factor-kappaB and the phosphorylation of extracellular
      signal-regulated protein kinases, the c-Jun N-terminal kinase, and p38,
      exhibiting anti-inflammatory antiapoptotic effects. Our results also further
      demonstrate that the proinflammatory cytokines of IL-1beta, IL-6, and TNF-alpha
      are promising targets for treatment of cerebral ischemic injury. Although further
      investigation is required for its development, all of these findings led us to
      speculate that mulberroside A is a candidate for the treatment of ischemic
      stroke, which would act as a multifactorial neuroprotectant.

PMID- 24687775
TI  - Direct (17)O MRI with partial volume correction: first experiences in a
      glioblastoma patient.
AB  - OBJECT: In tumor cells the energy production is shifted from aerobic to anaerobic
      metabolization of glucose, which makes the cerebral metabolic rate of oxygen
      consumption (CMRO2) a diagnostic parameter for tissue viability. Direct oxygen-17
      ((17)O) MRI during inhalation of (17)O gas allows for a non-invasive
      determination of the CMRO2. However, the low spatial resolution and the fast
      transverse relaxation of (17)O lead to partial volume effects that severely bias
      the quantification of signal intensities. The aim of this work was to determine
      the CMRO2 in a tumor patient by (17)O MRI in combination with a partial volume
      correction (PVC) scheme. MATERIALS AND METHODS: Direct (17)O MRI was performed in
      a glioblastoma patient (F, 51 years) prior to surgery at 7 T. The 'geometric
      transfer matrix' algorithm for volume of interest based PVC was adapted to (17)O
      MRI to recover the true signal intensities. We determined the CMRO2 values of
      gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and the tumor
      areas of the contrast enhancing rim (CE), the necrotic center (NE), and the
      perifocal edema (PE) using a three-phase metabolic model. RESULTS: Large
      differences in the signal increase during (17)O2 inhalation were obtained ranging
      from less than 2% in the tumor center up to more than 20% in GM areas. After PVC
      of the signal time curves, we determined CMRO2 values of 0.67 +/- 0.08
      MUmol/g/min (WM), 3.57 +/- 0.67 MUmol/g/min (GM), 0.35 +/- 0.09 MUmol/g/min (CE),
      and 0.42 +/- 0.05 MUmol/g/min (PE). In CSF and NE no oxygen uptake (i.e. CMRO2 =
      0) was determined from the corrected signals, well in accordance with the
      underlying physiology in these regions. CONCLUSION: The results show that PVC has
      a strong effect on the resulting CMRO2 values obtained by (17)O MRI. We found
      substantial differences-especially in GM tissue-between corrected and non
      corrected CMRO2 values. Additionally, we demonstrated the feasibility of CMRO2
      assessment in a glioblastoma patient by (17)O MRI.

PMID- 24687776
TI  - Vascular risk factors and midlife cognition: rethinking the exposure window.

PMID- 24687773
TI  - Can the freshwater bacterial communities shift to the "marine-like" taxa?
AB  - A mesocosm experiment was used to study the response of a freshwater bacterial
      community to increasing salinity. Bacterial community composition in the control
      and saline groups was analyzed using polymerase chain reaction (PCR)-terminal
      restriction fragment length polymorphism (T-RFLP) of the 16S rRNA genes, followed
      by clonal sequencing of eight selected samples. Cluster analysis and phylogenetic
      analysis revealed that the bacterial communities in pre- and post-salt addition
      samples were significantly different. Detailed analysis showed: (i) the existing
      bacterial taxa markedly declined from freshwater to hypersaline habitats,
      although some taxa maintain balanced growth over a small salinity range through
      inter-genus changes in community structures; (ii) the addition of salt induced a
      clear shift in the community structure toward a striking increase in the relative
      abundance of the latent "marine-like" genera (e.g., Alcanivorax and Roseovarius).
      The reasons may be that freshwater bacteria adapt to live in low salt
      concentrations and low osmotic pressure. They were not adapted to high
      concentrations of salt, and their acute response to increasing salinity resulted
      in significantly decreased numbers. However, as the salinity increases, rare
      members of the ever-present community (rare or dormant bacterial taxa in the
      "microbial seed bank") rise to the fore, while previous dominant members drop
      away. This study provides direct evidence for bacterial succession from
      halosensitive taxa in freshwater to halotolerant ones in response to water
      salinization. 

PMID- 24687777
TI  - Early adult to midlife cardiovascular risk factors and cognitive function.
AB  - BACKGROUND: Studies have linked midlife and late-life cardiovascular risk factors
      (CVRFs) to cognitive function, yet little is known about CVRF exposure in early
      adulthood and subsequent cognitive function. In addition, most studies rely on
      single assessments of CVRFs, which may not accurately reflect long-term exposure.
      We sought to determine the association between cumulative exposure to CVRFs from
      early to middle adulthood and cognitive function at midlife. METHODS AND RESULTS:
      In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25
      years of follow-up, we assessed cognitive function at year 25 (2010-2011) with
      the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning
      Test analyzed with standardized z scores. The primary predictor was 25-year
      cumulative exposure estimated by areas under the curve for resting systolic and
      diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher
      cumulative systolic and diastolic blood pressures and fasting blood glucose were
      consistently associated with worse cognition on all 3 tests. These associations
      were significant primarily for exposures above recommended guidelines; cognitive
      test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD
      increase in risk factor area under the curve after adjustment for age, race, sex,
      and education (P<0.05 for all). Fewer significant associations were observed for
      cholesterol. CONCLUSIONS: Cumulative exposure to CVRFs from early to middle
      adulthood, especially above recommended guidelines, was associated with worse
      cognition in midlife. The meaning of this association and whether it warrants
      more aggressive treatment of CVRFs earlier in life require further investigation.

PMID- 24687778
TI  - Genetic variations in MTHFR and esophageal squamous cell carcinoma susceptibility
      in Chinese Han population.
AB  - Esophageal cancer is the sixth most common cancer worldwide. Esophageal squamous
      cell carcinoma (ESCC) is a fatal malignancy associated with low 5-year survival
      rate. The aim of this study was to assess the association between
      methylenetetrahydrofolate reductase (MTHFR) tagging single nucleotide
      polymorphisms (SNPs) rs1801133 C>T, rs3753584 A>G, rs4845882 G>A, rs4846048 A>G
      and rs9651118 T>C genotypes and ESCC susceptibility in a hospital-based case
      control study. We conducted genotyping analyses for these five SNPs with 629 ESCC
      cases and 686 controls in a Chinese Han population. Ligation detection reaction
      method was used to identify genotypes of these MTHFR SNPs. Our results
      demonstrated that MTHFR rs1801133 C>T was associated with the risk of ESCC;
      however, MTHFR rs4845882 G>A and rs4846048 A>G SNPs were associated with the
      decreased risk of ESCC, and MTHFR rs3753584 A>G and rs9651118 T>C SNPs were not
      associated with ESCC risk. Our findings suggests that MTHFR rs1801133 C>T,
      rs4845882 G>A and rs4846048 A>G SNPs may be genetic modifiers for developing ESCC
      in Chinese Han population. 

PMID- 24687779
TI  - No association between XRCC3 Thr241Met and XPD Lys751Gln polymorphisms and the
      risk of colorectal cancer in West Algerian population: a case-control study.
AB  - Colorectal cancer (CRC) is a complex and multifactorial disease, in which genetic
      and environmental factors both seem to play a part. Many epidemiological studies
      have explored the association between genetic polymorphisms of X-ray repair cross
      complementing group 3 (XRCC3) (Thr241Met) and Xeroderma pigmentosum group D (XPD)
      lysine to glutamine at codon 751 (Lys751Gln) and risk of CRC in various
      populations; however, the results are controversial. We conducted this case
      control study in a West Algerian population to assess the potential role of this
      genetic polymorphism on the risk of CRC in this population. Genomic DNA was
      extracted from blood samples collected from 129 sporadic CRC patients and 148
      normal controls. The polymorphisms were determined by pyrosequencing technique.
      The distribution of XRCC3 Thr241Met and XPD Lys751Gln genotypes among controls
      did not differ significantly from those predicted by the Hardy-Weinberg
      distribution (p > 0.05). There were no significant differences in the genotypes
      distribution and allele frequencies between CRC patients and controls. A
      significant association was found between the combined heterozygous of XRCC3 and
      homozygous variant of XPD gene and CRC. This is the first study on DNA repair
      genetic polymorphisms in West Algerian population, and it suggests that the XRCC3
      Thr241Met and XPD Lys751Gln polymorphisms may not be associated with the CRC risk
      in this population.

PMID- 24687780
TI  - Distribution, origin, and transformation of metal and metalloid pollution in
      vegetable fields, irrigation water, and aerosols near a Pb-Zn mine.
AB  - Pollution of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb),
      and zinc (Zn) in vegetable fields was investigated near a Pb-Zn mine that has
      been exploited for over 50 years without a tailing reservoir. A total of 205
      water, soil, and aerosol samples were taken and quantified by combined chemical,
      spectrometric, and mineral analytical methods. The pollution origins were
      identified by Pb isotopes and the pathways of transformation and transport of the
      elements and minerals was studied. The data showed that the vegetable fields were
      seriously polluted by As, Cd, and Pb. Some concentrations in the samples were
      beyond the regulatory levels and not suitable for agricultural activities. This
      study revealed that: (1) particulate matter is a major pollution source and an
      important carrier of mineral particles and pollutants; (2) the elements from the
      polluted water and soils were strongly correlated with each other; (3) Pb isotope
      ratios from the samples show that Pb minerals were the major pollution sources in
      the nearby vegetable fields, and the aerosols were the main carrier of mining
      pollution; (4) the alkaline, rich-carbonate, and wet conditions in this area
      promoted the weathering and transformation of galena into the secondary minerals,
      anglesite and cerussite, which are significant evidence of such processes; (5)
      the soil and the aerosols are a recycled secondary pollution source for each
      other when being re-suspended with wind.Highlights* Mining activities generated
      heavy metal pollution in fields around a Pb-Zn mine* The elements from water and
      soils are strongly correlated* Anglesite and cerussite are evidence of galena
      transformation into secondary minerals* Particulate matter is an important
      transport carrier of pollution.

PMID- 24687781
TI  - Responses of kinetics and capacity of phenanthrene sorption on sediments to soil
      organic matter releasing.
AB  - Soil organic matter (SOM) releasing with dissolved organic matter (DOM) formed in
      solution was confirmed in a sediment/water system, and the effects of SOM
      releasing on the sorption of phenanthrene on sediments were investigated.
      Inorganic salt (0-0.1 mol L(-1) NaCl) was used to adjust SOM releasing, and two
      sediments were prepared, the raw sediment (S1) from Weihe River, Shann'xi, China,
      and the eluted sediments with and without DOM supernatant remained, termed as S2a
      and S2b, respectively. The FTIR and (1)H NMR analysis indicate that the low
      molecular weight hydrophilic SOM fraction released prior to the high molecular
      weight hydrophobic fraction. As a response, phenanthrene sorption kinetics on S1
      showed atypical and expressed as three stages: rapid sorption, pseudo sorption
      with partial desorption, and slow sorption, thus a defined "sorption valley"
      occurred in kinetic curve. In all cases, partition dominates the sorption, and
      sorption capacity (Kd) ranked as S2b > S1 > S2a. Compared with the alterations of
      sediment characters, DOM solubilization produced by SOM releasing exhibited a
      greater inhibitory effect on sorption with a relative contribution of 0.67.
      Distribution coefficients (K(doc)) of PHE into DOM clusters were 2.10 * 10(4)
      4.18 * 10(4) L kg(-1), however a threshold concentration of 6.83 mg L(-1) existed
      in DOM solubilization. The study results will help to clarify PAHs transport and
      their biological fate in a sediment/water system.

PMID- 24687782
TI  - Physiological and transcriptional responses of Baccharis halimifolia to the
      explosive "composition B" (RDX/TNT) in amended soil.
AB  - Unexploded explosives that include royal demolition explosive (RDX) and
      trinitrotoluene (TNT) cause environmental concerns for surrounding ecosystems.
      Baccharis halimifolia is a plant species in the sunflower family that grows
      naturally near munitions sites on contaminated soils, indicating that it might
      have tolerance to explosives. B. halimifolia plants were grown on 100, 300, and
      750 mg kg(-1) of soil amended with composition B (Comp B) explosive, a mixture of
      royal demolition explosive and trinitrotoluene. These concentrations are
      environmentally relevant to such munitions sites. The purpose of the experiment
      was to mimic contaminated sites to assess the plant's physiological response and
      uptake of explosives and to identify upregulated genes in response to explosives
      in order to better understand how this species copes with explosives. Stomatal
      conductance was not significantly reduced in any treatments. However, net
      photosynthesis, absorbed photons, and chlorophyll were significantly reduced in
      all treatments relative to the control plants. The dark-adapted parameter of
      photosynthesis was reduced only in the 750 mg kg(-1) Comp B treatment. Thus, we
      observed partial physiological tolerance to Comp B in B. halimifolia plants. We
      identified and cloned 11 B. halimifolia gene candidates that were orthologous to
      explosive-responsive genes previously identified in Arabidopsis and poplar. Nine
      of those genes showed more than 90% similarity to Conyza canadensis (horseweed),
      which is the closest relative with significant available genomics resources. The
      expression patterns of these genes were studied using quantitative real-time PCR.
      Three genes were transcriptionally upregulated in Comp B treatments, and the
      Cytb6f gene was found to be highly active in all the tested concentrations of
      Comp B. These three newly identified candidate genes of this explosives-tolerant
      plant species can be potentially exploited for uses in phytoremediation by
      overexpressing these genes in transgenic plants and, similarly, by using
      promoters or variants of promoters from these genes fused to reporter genes in
      transgenic plants for making phytosensors to report the localized presence of
      explosives in contaminated soils.

PMID- 24687783
TI  - Mercury in compact fluorescent lamps (CFLs): European legislation introduces an
      avoidable analytical bias.
AB  - European legislation has set a limit of 5 mg Hg per compact fluorescent lamp
      (CFL). Compliance with this regulation is tested with a method given in a
      European law from 2002 ("EU method"). According to the EU method, the arc tube
      has to be placed inside a fume cupboard and cut into segments. These pieces are
      collected and washed with HNO3, which is finally analyzed for Hg. In this study,
      we investigated the losses of Hg via the gas phase, which are ignored by the EU
      method, using a semiquantitative radiochemical neutron activation analysis (RNAA)
      technique developed at the TRIGA Mark II reactor in Vienna (Austria). Depending
      on the product, the losses range as high as approximately 2% at 20  degrees C. At
      higher ambient temperatures (hot summer days), the losses may increase by a
      factor of 4. Quality products generally suffer lower emission via the gas phase
      than cheap products, which is probably due to amalgam or other techniques that
      retain the Hg from broken CFLs. In any case, the EU method introduces a small but
      avoidable systematic error into the analysis and, in contrast to recommended
      practices, underestimates the Hg content of the CFL in question. Having technical
      alternatives at hand, we urge European lawmakers to adjust the law accordingly.

PMID- 24687784
TI  - Ultrasonic degradation of sulfadiazine in aqueous solutions.
AB  - Advanced oxidation methods, like ultrasound (US), are a promising technology for
      the degradation of emerging pollutants in water matrices, such as sulfonamide
      antibiotics. Nevertheless, few authors report the degradation of sulfonamides by
      high-frequency US (>100 kHz), and limited information exist concerning the use of
      ultrasonic-driven processes in the case of sulfadiazine (SDZ). In this study, SDZ
      degradation was investigated with the aim to evaluate the influence of initial
      concentration, pH and US frequency, and power. Ultrasonic frequencies of 580,
      862, and 1,142 kHz at different power values and SDZ initial concentrations of
      25, 50, and 70 mg L(-1) were used. The results show that SDZ degradation followed
      pseudo first-order reaction kinetics with k values and percent removals
      decreasing for increasing solute initial concentration. Higher SDZ percent
      removals and removal rates were observed for the lowest operating frequency (580
      kHz), higher dissipated power, and in slightly acidic solution (pH 5.5). Addition
      of the radical scavenger n-butanol confirmed that hydroxyl radical-mediated
      reactions at the interface of the cavitation bubbles are the prevailing
      degradation mechanism, which is directly related to the pKa-dependent speciation
      of SDZ molecules. Finally, addition of H2O2 had a detrimental effect on SDZ
      degradation, whereas the addition of the Fenton reagent showed a positive effect,
      revealing to be a promising alternative for the removal of sulfadiazine.

PMID- 24687785
TI  - Electro-Fenton degradation of the antibiotic sulfanilamide with Pt/carbon-felt
      and BDD/carbon-felt cells. Kinetics, reaction intermediates, and toxicity
      assessment.
AB  - The degradation of 230 mL of a 0.6-mM sulfanilamide solution in 0.05 M Na2SO4 of
      pH 3.0 has been studied by electro-Fenton process. The electrolytic cell
      contained either a Pt or boron-doped diamond (BDD) anode and a carbon-felt
      cathode. Under these conditions, organics are oxidized by hydroxyl radicals
      formed at the anode surface from water oxidation and in the bulk from Fenton's
      reaction between initially added (and then electrochemically regenerated) Fe(2+)
      and cathodically generated H2O2. From the decay of sulfanilamide concentration
      determined by reversed-phase liquid chromatography, an optimum Fe(2+)
      concentration of 0.20 mM in both cells was found. The drug disappeared more
      rapidly using BDD than Pt, and, in both cases, it was more quickly removed with
      raising applied current. Almost total mineralization was achieved using the
      BDD/carbon-felt cell, whereas the alternative use of Pt anode led to a slightly
      lower mineralization degree. In both cells, the degradation rate was accelerated
      at higher current but with the concomitant fall of mineralization current
      efficiency due to the greater increase in rate of the parasitic reactions of
      hydroxyl radicals. Reversed-phase liquid chromatography allowed the
      identification of catechol, resorcinol, hydroquinone, p-benzoquinone, and 1,2,4
      trihydroxybenzene as aromatic intermediates, whereas ion exclusion chromatography
      revealed the formation of malic, maleic, fumaric, acetic, oxalic, formic, and
      oxamic acids. NH4(+), NO3(-), and SO4(2-) ions were released during the electro
      Fenton process. A plausible reaction sequence for sulfanilamide mineralization
      involving all detected intermediates has been proposed. The toxicity of the
      solution was assessed from the Vibrio fischeri bacteria luminescence inhibition.
      Although it acquired its maximum value at short electrolysis time, the solution
      was completely detoxified at the end of the electro-Fenton treatment, regardless
      of the anode used.

PMID- 24687786
TI  - Electrolytic removal of Rhodamine B from aqueous solution by peroxicoagulation
      process.
AB  - Peroxicoagulation treatment of aqueous solution containing hazardous dye,
      Rhodamine B, with commercially available graphite as cathode and iron as anode
      has been studied. The effect of various operational parameters such as solution
      pH, applied voltage, electrode area, other ions, etc. on the dye removal was
      investigated. The experimental result showed that pH-regulated peroxicoagulation
      system is an efficient process for the dye removal. Ninety-five percent of the
      dye was removed after 180 min of electrolysis. Anions such as carbonate,
      bicarbonate, chloride and sulphate negatively affected the efficiency of
      peroxicoagulation system. From the present study, it can be concluded that
      peroxicoagulation process is an efficient tool for dye removal from aqueous
      solution.

PMID- 24687787
TI  - Scale-up of electrochemical oxidation system for treatment of produced water
      generated by Brazilian petrochemical industry.
AB  - Scale-up of anodic oxidation system is critical to the practical application of
      electrochemical treatment in bio-refractory organic wastewater treatment. In this
      study, the scale-up of electrochemical flow system was investigated by treating
      petrochemical wastewater using platinized titanium (Ti/Pt) and boron-doped
      diamond (BDD) anodes. It was demonstrated that flow cell was successfully scaled
      up because when it was compared with batch mode (Rocha et al. 2012b), higher
      performances on organic matter removal were achieved. Under the suitable
      operating conditions and better anode material, the chemical oxygen demand (COD)
      of petrochemical wastewater was reduced from 2,746 to 200 mg L(-1) within 5 h
      with an energy consumption of only 56.2 kWh m(-3) in the scaled-up BDD anode
      system. These results demonstrate that anode flow system is very promising in
      practical bio-refractory organic wastewater treatment.

PMID- 24687788
TI  - Electrochemical advanced oxidation processes: today and tomorrow. A review.
AB  - In recent years, new advanced oxidation processes based on the electrochemical
      technology, the so-called electrochemical advanced oxidation processes (EAOPs),
      have been developed for the prevention and remediation of environmental
      pollution, especially focusing on water streams. These methods are based on the
      electrochemical generation of a very powerful oxidizing agent, such as the
      hydroxyl radical ((*)OH) in solution, which is then able to destroy organics up
      to their mineralization. EAOPs include heterogeneous processes like anodic
      oxidation and photoelectrocatalysis methods, in which (*)OH are generated at the
      anode surface either electrochemically or photochemically, and homogeneous
      processes like electro-Fenton, photoelectro-Fenton, and sonoelectrolysis, in
      which (*)OH are produced in the bulk solution. This paper presents a general
      overview of the application of EAOPs on the removal of aqueous organic
      pollutants, first reviewing the most recent works and then looking to the future.
      A global perspective on the fundamentals and experimental setups is offered, and
      laboratory-scale and pilot-scale experiments are examined and discussed. 

PMID- 24687789
TI  - Oxidation of artificial sweetener sucralose by advanced oxidation processes: a
      review.
AB  - Sucralose, a chlorinated carbohydrate, has shown its increased use as an
      artificial sweetener and persistently exists in wastewater treatment plant
      effluents and aquatic environment. This paper aims to review possible degradation
      of sucralose and related carbohydrates by biological, electrochemical, chemical,
      and advanced oxidation processes. Biodegradation of sucralose in waterworks did
      not occur significantly. Electrochemical oxidation of carbohydrates may be
      applied to seek degradation of sucralose. The kinetics of the oxidation of
      sucralose and the related carbohydrates by different oxidative species is
      compared. Free chlorine, ozone, and ferrate did not show any potential to degrade
      sucralose in water. Advanced oxidation processes, generating highly strong
      oxidizing agent hydroxyl radicals ((*)OH), have demonstrated effectiveness in
      transforming sucralose in water. The mechanism of oxidation of sucralose by (*)OH
      is briefly discussed. 

PMID- 24687790
TI  - Treatment of Basic Red 29 dye solution using iron-aluminum electrode pairs by
      electrocoagulation and electro-Fenton methods.
AB  - The aim of this study is the treatment of Basic Red 29 (BR29) dye solution using
      hybrid iron-aluminum electrodes by electrocoagulation and electro-Fenton methods.
      The effect of current density, initial pH, supporting electrolyte, H2O2, and
      initial dye concentration on dye removal efficiency was investigated, and the
      best experimental conditions were obtained. Time-coarse variation of UV-Vis
      spectra and toxicity and chemical oxygen demand (COD) removal were also examined
      at the best experimental conditions. Both systems were found very successful for
      the removal of BR29 dye. The removal efficiency of >95% for BR29 dye solution was
      reached easily in a short time. At the best experimental conditions, for the
      initial BR29 concentration of 100 mg/L, >95% BR29 dye and 71.43% COD removal were
      obtained after 20 and 40 min of electrolysis, respectively. Additionally,
      toxicity results for electro-Fenton treatment of 100 mg/L BR29 were also very
      promising. According to the results obtained, although electro-Fenton is more
      effective, both systems can be used successfully to treat textile wastewater
      including dyes.

PMID- 24687791
TI  - Effect of matrix on the electrochemical characteristics of TiO2 nanotube array
      based PbO2 electrode for pollutant degradation.
AB  - A series of lead dioxide electrodes developed on titania nanotube arrays with
      different matrix were fabricated by electrodeposition. Before the deposition of
      PbO2, the matrix of this anode was electrochemically reduced in (NH4)2SO4
      solution and/or pre-deposited with certain amounts of copper. To gain insight
      into these pretreatments, the PbO2 electrodes were characterized by SEM, LSV, and
      XRD, and their electrocatalytic activities for pollutant degradation were
      compared using p-nitrophenol (p-NP) as a model. It was confirmed that the
      electrochemical reduction with (NH4)2SO4 resulted in the partial conversion of
      TiO2 into Ti4O7 and Ti5O9, which increased the conductivity of PbO2 anode, but
      decreased its electrochemical activity, while the Ti/TNTs*-Cu/PbO2 electrode with
      both pretreatments possessed the highest oxygen evolution overpotential of 2.5 V
      (vs. SCE) and low substrate resistance. After a 180-min treatment on this
      electrode, the removal efficiency of p-NP reached 82.5% and the COD removal
      achieved 42.5% with the energy consumption of 9.45 kWh m(-3), demonstrating the
      best performance among these electrodes with different matrices. Therefore, this
      titania nanotube array-based PbO2 electrode has a promising application in the
      industrial wastewater treatment.

PMID- 24687792
TI  - Kinetics of the degradation of n-butyl benzyl phthalate using O3/UV, direct
      photolysis, direct ozonation and UV effects.
AB  - The aim of this work is to study the degradation kinetics of the endocrine
      disruptor benzyl butyl phthalate using ozone and UV radiation. The model
      comprises four parallel subsystems that are identified and isolated: (1) direct
      photolysis, (2) direct ozonation in the absence of hydroxyl radicals, (3)
      complete ozonation (direct + indirect oxidation), and (4) ozone + UV. To
      determine the nature of ozone attacks and the influence of .OH radicals on O3
      activity, two sets of experiments were performed: (i) conventional ozonation and
      (ii) the same ozonation experiments in the presence of tert-butanol as radical
      scavenger, where only the reactions involving molecular ozone are present. The
      explored variables were (i) ozone concentration, (ii) incident radiation rate at
      the reactor windows, (iii) reaction pH, and (iv) the presence of radical
      scavengers. Major intermediates of BBP degradation were identified. Degradation
      kinetics was correctly modeled by a pseudo-second-order kinetic model based on
      the sum of all the effects occurring during the treatment. The corresponding
      kinetic constants were obtained, and the relative contributions of each of the
      considered subsystems were evaluated.

PMID- 24687793
TI  - Characterization of contaminants and evaluation of the suitability for land
      application of maize and sludge biochars.
AB  - Prior to the application of biochar as an agricultural improver, attention should
      be paid to the potential introduction of toxicants and resulting unintended
      impacts on the environment. In the present study, the concentrations of
      polycyclic aromatic hydrocarbons (PAHs), heavy metals, and mineral elements were
      determined in maize and sludge biochars produced at 100  degrees C increments
      between 200 and 700  degrees C. The concentration ranges of total PAHs were 358
      5,136 MUg kg(-1) in maize biochars and 179-70,385 MUg kg(-1) in sludge biochars.
      The total heavy metals were detected at the following concentrations (mg kg(-1)):
      Cu, 20.4-56.7; Zn, 59.7-133; Pb, 1.44-3.50; Cd, <0.014; Cr, 8.08-21.4; Ni, 4.38
      9.82 in maize biochars and Cu, 149-202; Zn, 735-986; Pb, 54.7-74.2; Cd, 1.06
      1.38; Cr, 180-247; Ni, 41.1-56.1 in sludge biochars. The total concentrations of
      PAHs and heavy metals in all maize biochars and most sludge biochars were below
      the control standards of sludge for agricultural use in China, the USA, and
      Europe. The leachable Mn concentrations in sludge biochars produced at below 500 
      degrees C exceeded the groundwater or drinking water standards of these
      countries. Overall, all the maize biochars were acceptable for land application,
      but sludge biochars generated at temperatures between 200 and 500  degrees C were
      unsuitable for application as soil amendments due to their potential adverse
      effects on soil and groundwater quality.

PMID- 24687794
TI  - Removal of antibiotics and antibiotic resistance genes in rural wastewater by an
      integrated constructed wetland.
AB  - Integrated constructed wetlands (ICWs) are regarded as one of the most important
      removal technology for pollutants in rural domestic wastewaters. This study
      investigated the efficiency of an ICW consisting of a regulating pool, four
      surface and subsurface flow-constructed wetlands, and a stabilization unit for
      removing antibiotics and antibiotic resistance genes (ARGs) from rural domestic
      wastewaters. The results showed that antibiotics leucomycin, ofloxacin,
      lincomycin, and sulfamethazine, and ARGs sul1, sul2, tetM, and tetO were the
      predominant antibiotics and ARGs in the influent, respectively. The ICW system
      could significantly reduce most of the detected antibiotics and ARGs with their
      aqueous removal rates of 78 to 100 % and >99 %, respectively. Based on the
      measured concentrations, the total pollution loadings of antibiotics were 3,479
      MUg/day in the influent and 199 MUg/day in the final effluent. Therefore,
      constructed wetlands could be a promising technology for rural wastewater in
      removing contaminants such as antibiotics and ARGs.

PMID- 24687795
TI  - Developmental toxicity of PAH mixtures in fish early life stages. Part I: adverse
      effects in rainbow trout.
AB  - A new gravel-contact assay using rainbow trout, Oncorhynchus mykiss, embryos was
      developed to assess the toxicity of polycyclic aromatic hydrocarbons (PAHs) and
      other hydrophobic compounds. Environmentally realistic exposure conditions were
      mimicked with a direct exposure of eyed rainbow trout embryos incubated onto
      chemical-spiked gravels until hatching at 10  degrees C. Several endpoints were
      recorded including survival, hatching delay, hatching success, biometry,
      developmental abnormalities, and DNA damage (comet and micronucleus assays). This
      bioassay was firstly tested with two model PAHs, fluoranthene and benzo[a]pyrene.
      Then, the method was applied to compare the toxicity of three PAH complex
      mixtures characterized by different PAH compositions: a pyrolytic extract from a
      PAH-contaminated sediment (Seine estuary, France) and two petrogenic extracts
      from Arabian Light and Erika oils, at two environmental concentrations, 3 and 10
      MUg g(-1) sum of PAHs. The degree and spectrum of toxicity were different
      according to the extract considered. Acute effects including embryo mortality and
      decreased hatching success were observed only for Erika oil extract. Arabian
      Light and pyrolytic extracts induced mainly sublethal effects including reduced
      larvae size and hemorrhages. Arabian Light and Erika extracts both induced
      repairable DNA damage as revealed by the comet assay versus the micronucleus
      assay. The concentration and proportion of methylphenanthrenes and
      methylanthracenes appeared to drive the toxicity of the three PAH fractions
      tested, featuring a toxic gradient as follows: pyrolytic < Arabian Light < Erika.
      The minimal concentration causing developmental defects was as low as 0.7 MUg g(
      1) sum of PAHs, indicating the high sensitivity of the assay and validating its
      use for toxicity assessment of particle-bound pollutants.

PMID- 24687796
TI  - (Eco)toxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) in
      zebrafish (Danio rerio) and permanent fish cell cultures.
AB  - 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a high-production volume chemical
      used in paper, ink, pesticide, and adhesive industries as a wetting and anti
      foaming agent. The physicochemical properties and slow biodegradation rate of
      TMDD indicate a low bioaccumulation potential but a high prevalence in the
      environment. As a consequence, TMDD has been detected in several European rivers
      in the nanogram per liter and lower microgram per liter range; however, its
      environmental risk to aquatic organisms is considered low. Recent studies almost
      exclusively focused on acute effects by TMDD, little is known about cytotoxic and
      genotoxic effects, reproduction and developmental toxicity, endocrine disruption,
      and any kind of long-term toxicity and carcinogenicity so far. The present study
      aims to provide more specific baseline information on the ecotoxicological
      effects of TMDD in fish. For this end, cyto- and genotoxicity assays were carried
      out in vitro with the permanent fish cell line RTL-W1; in addition, in vivo
      studies were conducted with the early life stages of zebrafish (Danio rerio) in
      order to fill the data gaps in developmental toxicity and endocrine disruption.
      TMDD showed a cytotoxic and slight genotoxic potential in fish cell lines;
      moreover, various sublethal and lethal effects could be detected in developing
      zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD;
      however, mortality following prolonged exposure to TMDD during fish sexual
      development test was clearly higher than mortality in the fish embryo test after
      96-h exposure. Our results thus confirmed previous findings of laboratory
      screening tests, suggesting short-term toxic effects of TMDD in the intermediate,
      and long-term effects in the lower milligram per liter range. 

PMID- 24687797
TI  - Levels and distribution of heavy metals in atmospheric particular matters over
      the northern South China Sea.
AB  - Oceans play a significant role in the cycling of trace metals and persistent
      organic pollutants. In this study, aerosol samples covering the whole northern
      South China Sea (SCS) were collected in 2005 and 2007, respectively, for analysis
      of trace metals and major elements. The levels of trace metals detected ranged
      from 0.514 to 119 ng/m(3) in 2005 and from 0.130 to 24.2 ng/m(3) in 2007,
      respectively. Cu, Zn, and Pb were the three predominant metals with high
      enrichment factors (>10), indicating the strong anthropogenic inputs. The trace
      metals over SCS were comparable to the values in suburban and background sites of
      South China, but generally higher than those over other seas and oceans.
      Considering the fact that they were influenced by their proximity to source
      regions and air mass origins, the elevated metals in 2005 were probably
      attributed to the strong wind and long-range atmospheric transport driven by
      Asian monsoon.

PMID- 24687798
TI  - Soil concentrations and source apportionment of polybrominated diphenyl ethers
      (PBDEs) and trace elements around a heavily industrialized area in Kocaeli,
      Turkey.
AB  - Air pollutants are transported by dry deposition, wet deposition, and gas
      exchange accumulated in soil. Therefore, soil is an important environmental
      medium reflecting the level and the spatial distribution of air pollutants such
      as polybrominated diphenyl ethers (PBDEs) and heavy metals. Soil concentrations
      of seven PBDE congeners and 21 trace elements were determined in a heavily
      industrialized region (Dilovasi) in Kocaeli, Turkey. At all sites, Sigma7PBDE
      concentrations ranged from 0.70 to 203 with a mean value of 26.3 MUg kg(-1) (dry
      weight). The congener profiles and mass inventories of PBDEs and their
      interactions with soil organic matter (SOM) were also investigated. BDE-209 was
      the dominant congener at all sites, followed by BDE-99 and/or -47. The estimated
      inventory of PBDEs for the Dilovasi district was 310 kg. However, there are
      several additional industrial regions in Kocaeli city. Considering the total land
      area, the potential inventory would be much larger for this city. The
      relationship between the PBDE concentrations in soil and SOM content indicated
      that factors other than soil properties have a greater influence on soil
      concentrations. Crustal enrichment factors (EFs) were determined; correlation
      analysis and factor analysis (FA) were also applied to generated data set to
      identify and apportion the sources polluting the soil. Sn, Mn, Ca, As, Zn, Pb,
      and Cd had significantly high average EF values, indicating that their soil
      concentrations were mainly influenced by anthropogenic activities. In FA, six
      factors were extracted with a cumulative variance of 84.4 % and industrial
      activities and traffic were found to be the main factors affecting the soil
      profile.

PMID- 24687799
TI  - nab-Paclitaxel: novel clinical and experimental evidence in pancreatic cancer.
AB  - The past few decades have seen virtually no treatment advances for patients with
      metastatic pancreatic cancer. Clinical hallmark features of pancreatic ductal
      adenocarcinoma (PDA) include late symptom onset, invasive growth, early liver and
      lymph node metastasis, and resistance to available chemotherapies. nab-Paclitaxel
      (Abraxane(r)) is generated through high-pressure homogenization of human albumin
      and conventional paclitaxel resulting in non-covalently bound, water-soluble
      albumin-paclitaxel particles with an approximate diameter of 130 nm. Results from
      the recently completed Metastatic Pancreatic Adenocarcinoma Trial (MPACT) (phase
      III trial) showed a significant survival benefit for patients treated with nab
      paclitaxel in combination with gemcitabine, and this treatment regimen is
      currently being implemented in national and international guidelines for PDA
      patients. Therefore, this regimen provides a much needed vantage point of attack
      for this recalcitrant tumor offering potential new hope for our patients.
      Mechanisms such as stromal depletion, selective intratumoral accumulation,
      synergism with gemcitabine metabolism and secreted protein acidic and rich in
      cysteine (SPARC) mediated anti-tumor activity have been suggested for nab
      paclitaxel. This review discusses the clinical and experimental advances of nab
      paclitaxel in pancreatic cancer. 

PMID- 24687800
TI  - Photosensitizing effects of hypericin on head neck squamous cell carcinoma in
      vitro.
AB  - Clinical outcome of patients suffering from head neck squamous cell carcinomas is
      still poor due to recurrent disease and surgical limitations. There is still a
      demand for multimodality approaches and new therapeutic options. Hypericin is a
      promising phototoxic drug which was investigated for its effects on head neck
      squamous cell carcinoma cells in vitro. FaDu cells incubated with or without
      hypericin were illuminated (450-700 nm, 50,000 lx) for different time periods. 3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide- and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to
      score metabolic and apoptotic activity. Even after the shortest illumination FaDu
      cells incubated with hypericin showed massive reduction of metabolism and
      excessive apoptosis. This was present even with the lowest hypericin
      concentration. Cells without hypericin or without illumination were not affected.
      These photosensitizing effects of hypericin could be suitable for clinical
      application and could lead to the development of an intraoperative photodynamic
      therapy of head neck squamous cell carcinomas.

PMID- 24687801
TI  - Multiple chemical sensitivity worsens quality of life and cognitive and sensorial
      features of sense of smell.
AB  - Multiple chemical sensitivity (MCS) is characterized by a loss of tolerance to a
      variety of environmental chemicals. Multiple chemical sensitivity is frequently
      triggered by exposure to chemical agents, especially insecticides. The aim of the
      study was to measure the sense of smell and quality of life in patients with MCS
      compared to the control group. We studied the sense of smell, both sensitive and
      sensorial characteristics, in female patients with MCS (n = 58, mean 50.5 +/- 8.5
      years) and healthy female volunteers without rhinosinusal pathologies (n = 60,
      mean age 46 +/- 10.2 years). Olfactometry (Barcelona Smell Test 24/BAST-24),
      sinonasal symptoms (visual analogue scale/VAS 0-100 mm), and quality of life
      (Quick Environmental Exposure and Sensitivity Inventory/QEESI) were assessed.
      Multiple chemical sensitivity patients showed a significant impairment in smell
      identification (19 +/- 12 %; p > 0.05) and forced choice (62 +/- 18 %; p > 0.05),
      but not in smell detection (96 +/- 4 %) compared to the control group. Multiple
      chemical sensitivity patients reported more odours as being intense and
      irritating and less fresh and pleasant when compared with the control group.
      Patients scored a high level (40-100) on QEESI questionnaire (symptom severity,
      chemical intolerances, other intolerances, life impact). In MCS patients, total
      symptom intensity (VAS/0-700 mm) score was 202 +/- 135, while disease severity
      score was 80 +/- 23. The most frequent symptoms were itching and posterior
      rhinorrhea. Multiple chemical sensitivity patients have an impairment in smell
      cognitive abilities (odour identification and forced choice, but not for
      detection) with increased smell hypersensitivity and poor quality of life.

PMID- 24687802
TI  - Comparison of the tolerance of hepatic ischemia/reperfusion injury in living
      donors: macrosteatosis versus microsteatosis.
AB  - A safe use of intermittent hepatic inflow occlusion (IHIO) has been reported for
      living donor hepatectomy. However, it remains unclear whether the maneuver is
      safe in steatotic donors. In addition, the respective importance of
      macrosteatosis (MaS) and microsteatosis (MiS) is an important issue. Thus, we
      compared MiS and MaS with respect to the tolerance of hepatic
      ischemia/reperfusion (IR) injury induced by IHIO. One hundred forty-four donors
      who underwent a right hepatectomy were grouped according to the presence of MaS
      and MiS: a non-MaS group (n = 68) versus an MaS group (n = 76) and a non-MiS
      group (n = 51) versus an MiS group (n = 93). The coefficients of the regression
      lines between the cumulative IHIO time and the peak postoperative transaminase
      concentrations were used as surrogate parameters indicating the tolerance of
      hepatic IR injury. The coefficients were significantly greater for the MaS group
      versus the non-MaS group (4.12 +/- 0.59 versus 2.22 +/- 0.46 for alanine
      aminotransferase, P = 0.01). Conversely, the MiS and non-MiS groups were
      comparable. A subgroup analysis of donors who underwent IHIO for >30 minutes
      showed that MaS significantly increased the transaminase concentrations, whereas
      MiS had no impact. Also, IHIO for >30 minutes significantly increased the biliary
      complication rate for MaS donors (12.1% for <= 30 minutes versus 32.6% for >30
      minutes, P = 0.04), whereas MiS donors were not affected. In conclusion, the
      tolerance of hepatic IR injury might differ between MaS livers and MiS livers. It
      would be rational to assign more clinical importance to MaS versus MiS. We
      further recommend limiting the cumulative IHIO time to 30 minutes or less for MaS
      donors undergoing right hepatectomy.

PMID- 24687803
TI  - Public health capacity in the provision of health care services.
AB  - In this paper, we assess the capacity of Florida's public health departments. We
      achieve this by using bootstrapped data envelopment analysis (DEA) applied to
      Johansen's definition of capacity utilization. Our purpose in this paper is to
      measure if there is, theoretically, enough excess capacity available to handle a
      possible surge in the demand for primary care services especially after the
      implementation of the Affordable Care Act that includes provisions for expanded
      public health services. We measure subunit service availability using a
      comprehensive data source available for all 67 county health departments in the
      provision of diagnostic care and primary health care. In this research we aim to
      address two related research questions. First, we structure our analysis so as to
      fix budgets. This is based on the assumption that State spending on social and
      health services could be limited, but patient needs are not. Our second research
      question is that, given the dearth of primary care providers in Florida if
      budgets are allowed to vary is there enough medical labor to provide care to
      clients. Using a non-parametric approach, we also apply bootstrapping to the
      concept of plant capacity which adds to the productivity research. To preview our
      findings, we report that there exists excess plant capacity for patient treatment
      and care, but question whether resources may be better suited for more
      traditional types of public health services. 

PMID- 24687804
TI  - No evidence for an association of osteopontin plasma levels with disease activity
      in multiple sclerosis.

PMID- 24687805
TI  - Stressful life-events in childhood and risk of multiple sclerosis: a Danish
      nationwide cohort study.
AB  - BACKGROUND: Current knowledge concerning the association between exposure to
      stressful life-events (SFLEs) in childhood and later risk of multiple sclerosis
      (MS) is sparse. OBJECTIVES: We studied the associations between SFLEs in
      childhood and subsequent risk of MS in a nationwide cohort of 2.9 million Danes
      born from 1968 to 2011. METHODS: A SFLE in childhood was defined as exposure
      before age 18 years to parental divorce, parental death, or death of a sibling,
      using information from the Danish Civil Registration System. MS cases in the
      cohort were identified in the Danish Multiple Sclerosis Registry. Associations of
      SFLE with MS risk were evaluated by incidence rate ratios (RR) of MS obtained in
      log-linear Poisson regression models. RESULTS: Persons exposed to any SFLE in
      childhood were at 11% elevated risk of MS (RR = 1.11; 95% confidence interval:
      1.03-1.20), compared to non-exposed persons. Stratification by subtype of SFLE
      showed that parental death and death of a sibling were not associated with MS
      risk. However, persons exposed to parental divorce were at 13% increased risk of
      developing MS compared to non-exposed (RR = 1.13; 1.04-1.23). CONCLUSIONS:
      Associations of SFLEs in childhood with risk of MS are weak. However, parental
      divorce is somehow associated with modestly increased risk of MS.

PMID- 24687806
TI  - The onset location of neuromyelitis optica spectrum disorder predicts the
      location of subsequent relapses.
AB  - We evaluated whether the location of the initial attack predicted the locations
      of subsequent events in neuromyelitis optica spectrum disorder (NMOSD). In the
      retrospective analysis from 164 patients with NMOSD, increased odds of a second
      attack occurring in the initial event location were seen in all locations (odds
      ratio [OR] brain: 16.00; brainstem: 4.42; optic nerve: 4.08; and spinal cord:
      4.59), as was a positive linear trend when evaluating the number of previous
      events in the same location as the third event location (OR brain: 62.52;
      brainstem: 44.55; optic nerve: 6.48; and spinal cord: 2.98). This study suggests
      early clinical events of NMOSD tend to recur in the same anatomical location
      within the central nervous system (CNS). 

PMID- 24687808
TI  - Clinical and molecular aspects of the live attenuated Oka varicella vaccine.
AB  - VZV is a ubiquitous member of the Herpesviridae family that causes varicella
      (chicken pox) and herpes zoster (shingles). Both manifestations can cause great
      morbidity and mortality and are therefore of significant economic burden. The
      introduction of varicella vaccination as part of childhood immunization programs
      has resulted in a remarkable decline in varicella incidence, and associated
      hospitalizations and deaths, particularly in the USA. The vaccine preparation,
      vOka, is a live attenuated virus produced by serial passage of a wild-type
      clinical isolate termed pOka in human and guinea pig cell lines. Although vOka is
      clinically attenuated, it can cause mild varicella, establish latency, and
      reactivate to cause herpes zoster. Sequence analysis has shown that vOka differs
      from pOka by at least 42 loci; however, not all genomes possess the novel vOka
      change at all positions, creating a heterogeneous population of genetically
      distinct haplotypes. This, together with the extreme cell-associated nature of
      VZV replication in cell culture and the lack of an animal model, in which the
      complete VZV life cycle can be replicated, has limited studies into the molecular
      basis for vOka attenuation. Comparative studies of vOka with pOka replication in
      T cells, dorsal root ganglia, and skin indicate that attenuation likely involves
      multiple mutations within ORF 62 and several other genes. This article presents
      an overview of the clinical aspects of the vaccine and current progress on
      understanding the molecular mechanisms that account for the clinical phenotype of
      reduced virulence.

PMID- 24687807
TI  - Longitudinal evaluation of cognitive functioning in pediatric multiple sclerosis:
      report from the US Pediatric Multiple Sclerosis Network.
AB  - BACKGROUND: Approximately one-third of those with pediatric-onset multiple
      sclerosis (MS) experience cognitive impairment. Less is known concerning their
      change in cognitive functioning over time. OBJECTIVE: Changes in cognitive
      function over time were measured in the largest pediatric cohort to date through
      the US Network of Pediatric MS Centers. METHODS: A total of 67 individuals with
      pediatric MS (n=62) or clinically isolated syndrome (CIS, n=5), ranging from 8-17
      years of age (mean age +/- standard deviation (SD)=14.37 +/- 2.02) completed
      initial and follow-up neuropsychological testing after an average of 1.64 +/-
      0.63 years apart. The nine tests administered measure general intellect,
      attention and working memory, verbal memory, visuomotor integration, language,
      and executive functioning. RESULTS: Rate of impairment (having one-third or more
      scores in the impaired range) was 37% at baseline and 33% at follow-up. Tests
      commonly impaired were measures of visuomotor integration, speeded processing,
      and attention. Most tested did not decline over two years. There was no clear
      pattern of change on any specific measure. CONCLUSION: Findings suggest that,
      over short timeframes, stable or even improved performances on measures of
      cognitive ability can occur. Pediatric MS may instead prevent expected age
      related cognitive gains.

PMID- 24687809
TI  - Overfeeding increases postprandial endotoxemia in men: Inflammatory outcome may
      depend on LPS transporters LBP and sCD14.
AB  - SCOPE: Low-grade inflammation is a recognized hallmark of obesity. Endotoxins
      absorbed after high-fat meals have recently been implicated. Plasma
      lipopolysaccharides binding protein (LBP) and soluble cluster of differentiation
      14 (sCD14) have also been suggested as clinical markers of endotoxemia. In mice,
      the ratio LBP/sCD14 has been associated with high fat diet induced inflammation.
      We tested the hypothesis that healthy subjects develop inflammation differently
      during weight gain according to changes of LBP/sCD14 ratio. METHODS AND RESULTS:
      Eighteen healthy men were overfed during 8 wk (+760 kcal/day). Endotoxemia,
      sCD14, LBP, and IL-6 were measured before and after overfeeding (OF) at fasting
      (n = 18) and postprandially (subcohort, n = 8). OF did not modify fasting IL-6
      but increased the LBP/sCD14 ratio (P = 0.017). Subjects were categorized into
      tertiles for LBP/sCD14 ratio variation. Subjects in the highest tertile (+90%
      LBP/sCD14) increased plasma IL-6 (+26%) versus the lowest tertile due to a
      decrease of sCD14 associated with high LBP. The postprandial accumulation of
      endotoxins increased after OF (+160%). However, only four responding subjects
      presented increased postprandial IL-6 accumulation. CONCLUSION: OF increases
      postprandial endotoxemia but the inflammatory outcome may be modulated by
      endotoxin handling in plasma. This study supports a new concept whereby
      inflammation setup during the initial phase of weight gain is linked to the
      relative variations of LBP and sCD14.

PMID- 24687810
TI  - A step-wise approach to deep brain stimulation in mice.
AB  - BACKGROUND: Studies of deep brain stimulation (DBS) in mice are rare due to their
      small size, agility, aversion to handling, and high anxiety compared to larger
      species. Studying DBS modulation of neural circuitry in murine models of human
      behavior may ensure safety, guide stimulatory parameters for clinical trials in
      humans, and inform a long-eluded mechanism. METHODS: Stereotactic deep brain
      electrode implantation in a mouse is performed. Mechanical etching of the skull
      with a high-speed drill is used with placement of cyanoacrylate glue and molding
      of dental acrylate to affix the electrode in place. Stimulation experiments are
      conducted in the home cage after a habituation period. After testing is complete,
      electrode placement is verified in fixed tissue. RESULTS: Electrodes can be
      safely and accurately implanted in mice for DBS experimentation. Previous
      findings demonstrated accuracy in placement within the nucleus accumbens shell of
      93 % [14]. In this study, there were no hardware malfunctions that required
      interrupting experimentation. CONCLUSIONS: Stereotactic DBS studies may be safely
      and effectively performed in mice to investigate neuropsychiatric disorders. In
      addition, examining the biochemical and molecular mechanisms underlying these
      disorders may be facilitated by widely available transgenic mouse lines and the
      Cre-Lox recombination system.

PMID- 24687811
TI  - Intraventricular stent migration--a problem solved by the use of subcutaneous
      reservoirs.

PMID- 24687812
TI  - Reply: Left-sided and duplicate inferior vena cava: a case series and review.

PMID- 24687813
TI  - Primary oral melanoma presenting with cervical lymph node metastasis: a rare case
      report with emphasis on the role of FNA in the diagnostic approach.

PMID- 24687815
TI  - Tuning the electronic nature of mono-bay alkynyl-phenyl-substituted perylene
      bisimides: synthesis, structure, and photophysical properties.
AB  - Perylene bisimide (PBI) derivatives with various alkynyl-phenyl substituents at a
      single bay position have been synthesised by Sonogashira coupling. NMR
      spectroscopic studies reveal the unsymmetric nature of the dyads. All of the
      dyads undergo two reversible reductions, which demonstrates their structural and
      electrochemical rigidity. The synthesised dyads show a remarkable redshift in
      their absorption maxima and sharp vibronic progression. Electron-rich
      substituents facilitate efficient charge transfer from the substituent HOMO to
      the electron-deficient PBI core. The most interesting spectral signatures were
      exhibited by a PBI with a strongly electron-donating ethynyl(dimethylaminophenyl)
      substituent. The steady-state features of this PBI showed a broad absorption that
      covered almost the whole visible region with no emission. A twisted
      intramolecular charge-transfer (TICT) process, related to the rotational motion
      of ethynyl(dimethylaminophenyl) PBI, was also demonstrated. Computational
      investigations shed light on the coplanarity of the various substituents with
      respect to the PBI core; the PBI core itself remains flat without any noticeable
      deformation even after mono-functionalisation. This illustrates that mono
      functionalisation exerts meagre steric hindrance on the bay positions relative to
      disubstituted analogues. Despite several previous reports on the structural
      characterisation of 1,7-disubstituted PBI derivatives, we present the first
      structural characterisation of a mono-bay ethynyl-phenyl substituted PBI. The
      solid-state structure of the phenyl derivative has a flat PBI core without any
      noticeable steric constraints from the substituents, as predicted. In contrast,
      single-crystal X-ray analysis for the mono-bromo bay-substituted PBI shows that
      the bromine substituent is not in the plane of the PBI core. 

PMID- 24687814
TI  - The power of neuroimaging biomarkers for screening frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous
      neurodegenerative disease that can result from either frontotemporal lobar
      degeneration (FTLD) or Alzheimer's disease (AD) pathology. It is critical to
      establish statistically powerful biomarkers that can achieve substantial cost
      savings and increase the feasibility of clinical trials. We assessed three broad
      categories of neuroimaging methods to screen underlying FTLD and AD pathology in
      a clinical FTD series: global measures (e.g., ventricular volume), anatomical
      volumes of interest (VOIs) (e.g., hippocampus) using a standard atlas, and data
      driven VOIs using Eigenanatomy. We evaluated clinical FTD patients (N = 93) with
      cerebrospinal fluid, gray matter (GM) magnetic resonance imaging (MRI), and
      diffusion tensor imaging (DTI) to assess whether they had underlying FTLD or AD
      pathology. Linear regression was performed to identify the optimal VOIs for each
      method in a training dataset and then we evaluated classification sensitivity and
      specificity in an independent test cohort. Power was evaluated by calculating
      minimum sample sizes required in the test classification analyses for each model.
      The data-driven VOI analysis using a multimodal combination of GM MRI and DTI
      achieved the greatest classification accuracy (89% sensitive and 89% specific)
      and required a lower minimum sample size (N = 26) relative to anatomical VOI and
      global measures. We conclude that a data-driven VOI approach using Eigenanatomy
      provides more accurate classification, benefits from increased statistical power
      in unseen datasets, and therefore provides a robust method for screening
      underlying pathology in FTD patients for entry into clinical trials.

PMID- 24687816
TI  - Physiological networks and disease functions of RNA-binding protein AUF1.
AB  - Regulated messenger RNA (mRNA) decay is an essential mechanism that governs
      proper control of gene expression. In fact, many of the most physiologically
      potent proteins are encoded by short-lived mRNAs, many of which contain AU-rich
      elements (AREs) in their 3'-untranslated region (3'-UTR). AREs target mRNAs for
      post-transcriptional regulation, generally rapid decay, but also stabilization
      and translation inhibition. AREs control mRNA turnover and translation activities
      through association with trans-acting RNA-binding proteins that display high
      affinity for these AU-rich regulatory elements. AU-rich element RNA-binding
      protein (AUF1), also known as heterogeneous nuclear ribonucleoprotein D (HNRNPD),
      is an extensively studied AU-rich binding protein (AUBP). AUF1 has been shown to
      regulate ARE-mRNA turnover, primarily functioning to promote rapid ARE-mRNA
      degradation. In certain cellular contexts, AUF1 has also been shown to regulate
      gene expression at the translational and even the transcriptional level. AUF1
      comprises a family of four related protein isoforms derived from a common pre
      mRNA by differential exon splicing. AUF1 isoforms have been shown to display
      multiple and distinct functions that include the ability to target ARE-mRNA
      stability or decay, and transcriptional activation of certain genes that is
      controlled by their differential subcellular locations, expression levels, and
      post-translational modifications. AUF1 has been implicated in controlling a
      variety of physiological functions through its ability to regulate the expression
      of numerous mRNAs containing 3'-UTR AREs, thereby coordinating functionally
      related pathways. This review highlights the physiological functions of AUF1
      mediated regulation of mRNA and gene expression, and the consequences of
      deficient AUF1 levels in different physiological settings.

PMID- 24687817
TI  - Preserve the (intraocular) environment: the importance of maintaining normal
      oxygen gradients in the eye.
AB  - Oxygen levels in the eye are generally low and tightly regulated. Oxygen enters
      the eye largely by diffusion from retinal arterioles and through the cornea. In
      intact eyes, oxygen from the retinal arterioles diffuses into the vitreous body.
      There is a decreasing oxygen gradient from the retina to the lens, established by
      oxygen consumption by ascorbate in the vitreous fluid and lens metabolism. Age
      related degeneration of the vitreous body or removal during vitrectomy exposes
      the posterior of the lens to increased oxygen, causing nuclear sclerotic
      cataracts. Lowering oxygen in the vitreous, as occurs in patients with ischemic
      diabetic retinopathy, protects against cataracts after vitrectomy. Vitrectomy and
      cataract surgery increase oxygen levels at the trabecular meshwork and with it
      the risk of open angle glaucoma. Two additional risk factors for glaucoma,
      African heritage and having a thinner cornea, are also associated with increased
      oxygen in the anterior chamber angle. Preservation of the vitreous body and the
      lens, two important oxygen consumers, would protect against nuclear sclerotic
      cataracts and open angle glaucoma. Delaying removal of the lens for as long as
      possible after vitrectomy would be an important step in delaying ocular
      hypertension and glaucoma progression. 

PMID- 24687818
TI  - Cholesterol oxidase production from entrapped cells of Streptomyces sp.
AB  - Production of cholesterol oxidase (COD) under batch conditions through Ca
      alginate immobilized cells of Streptomyces sp. was investigated. The process was
      studied for optimal immobilization conditions, beads operational stability and
      comparisons were made with the COD production via free cells. Influence of Na
      alginate concentration (1-5 g L(-1) ) and initial biomass loading on enzyme
      production were studied. Effects of initial pH of the production medium,
      temperature, shaker speed, as well as reuse of beads on the COD production were
      also investigated. It was observed that COD production with immobilized cells
      (5.6 U ml(-1) ) was higher in comparison to free cells (4.5 U ml(-1) ) under
      optimized conditions. The maximum COD production by free cells was observed with
      initial pH 7.0, rpm 200 after 96 h of incubation while immobilized cells sustain
      a broad pH range 6.0-9.0, rpm 300 for maximum production after 72 h. The
      immobilized and free cells produced maximum COD in the culture incubated at 37
      and 30  degrees C, respectively. Other parameters bead size and Na-alginate
      concentration found to be optimum with 1.5 mm and 4% w/v, respectively. Scanning
      electron microscope study of the immobilized cells indicated that the cells in Ca
      alginate beads remained in normal shape with no alterations in the morphology. 

PMID- 24687819
TI  - Impending Carotid Blowout Syndrome.

PMID- 24687820
TI  - Nutritional status as a prognostic indicator for pediatric malignancies.

PMID- 24687821
TI  - Too much, too little, or just right? Tumor margins in women undergoing breast
      conserving surgery.

PMID- 24687823
TI  - Setting the bar for therapeutic trials in non-small-cell lung cancer: how low can
      we go?

PMID- 24687822
TI  - KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance
      in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT
      Dysregulation.

PMID- 24687824
TI  - Will focal therapy remain only an attractive illusion for the primary treatment
      of prostate cancer?

PMID- 24687825
TI  - Olfactory Neuroblastoma With Hyponatremia.

PMID- 24687826
TI  - Randomized, controlled, double-blind, cross-over trial assessing treatment
      preference for pazopanib versus sunitinib in patients with metastatic renal cell
      carcinoma: PISCES Study.
AB  - PURPOSE: Patient-reported outcomes may help inform treatment choice in
      advanced/metastatic renal cell carcinoma (RCC), particularly between approved
      targeted therapies with similar efficacy. This double-blind cross-over study
      evaluated patient preference for pazopanib or sunitinib and the influence of
      health-related quality of life (HRQoL) and safety factors on their stated
      preference. PATIENTS AND METHODS: Patients with metastatic RCC were randomly
      assigned to pazopanib 800 mg per day for 10 weeks, a 2-week washout, and then
      sunitinib 50 mg per day (4 weeks on, 2 weeks off, 4 weeks on) for 10 weeks, or
      the reverse sequence. The primary end point, patient preference for a specific
      treatment, was assessed by questionnaire at the end of the two treatment periods.
      Other end points and analyses included reasons for preference, physician
      preference, safety, and HRQoL. RESULTS: Of 169 randomly assigned patients, 114
      met the following prespecified modified intent-to-treat criteria for the primary
      analysis: exposure to both treatments, no disease progression before cross over,
      and completion of the preference questionnaire. Significantly more patients
      preferred pazopanib (70%) over sunitinib (22%); 8% expressed no preference (P <
      .001). All preplanned sensitivity analyses, including the intent-to-treat
      population, statistically favored pazopanib. Less fatigue and better overall
      quality of life were the main reasons for preferring pazopanib, with less
      diarrhea being the most cited reason for preferring sunitinib. Physicians also
      preferred pazopanib (61%) over sunitinib (22%); 17% expressed no preference.
      Adverse events were consistent with each drug's known profile. Pazopanib was
      superior to sunitinib in HRQoL measures evaluating fatigue, hand/foot soreness,
      and mouth/throat soreness. CONCLUSION: This innovative cross-over trial
      demonstrated a significant patient preference for pazopanib over sunitinib, with
      HRQoL and safety as key influencing factors.

PMID- 24687828
TI  - Later stage at diagnosis and worse survival in cutaneous malignant melanoma among
      men living alone: a nationwide population-based study from Sweden.
AB  - PURPOSE: To investigate the association between cohabitation status, clinical
      stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma
      (CMM). METHODS: This nationwide population-based study included 27,235 patients
      from the Swedish Melanoma Register diagnosed with a primary invasive CMM between
      1990 and 2007 and linked data to nationwide, population-based registers followed
      up through 2012. RESULTS: After adjustment for age at diagnosis, level of
      education, living area, period of diagnosis, and tumor site, the odds ratios
      (ORs) of higher stage at diagnosis were significantly increased among men living
      alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI,
      1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR
      for stage II versus stage I disease was also increased among women living alone
      (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed
      earlier, the CMM-specific survival was significantly decreased among men living
      alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After
      additional adjustments for all potential and established prognostic factors, CMM
      specific survival among men living alone versus men living with a partner
      remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001),
      suggesting a residual adverse effect on survival not accounted for by these
      parameters. CONCLUSION: In all age groups among men, living alone is
      significantly associated with reduced CMM-specific survival, partially attributed
      to a more advanced stage at diagnosis. This emphasizes the need for improved
      prevention and early detection strategies for this group.

PMID- 24687827
TI  - Remarkable Response to Crizotinib in Woman With Anaplastic Lymphoma Kinase
      Rearranged Anaplastic Thyroid Carcinoma.

PMID- 24687829
TI  - Patient-reported outcome results from the open-label phase III AURELIA trial
      evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer.
AB  - PURPOSE: To determine the effects of bevacizumab on patient-reported outcomes
      (PROs; secondary end point) in the AURELIA trial. PATIENTS AND METHODS: Patients
      with platinum-resistant ovarian cancer were randomly assigned to chemotherapy
      alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire
      Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer
      Therapy-Ovarian Cancer symptom index (FOSI) at baseline and every two or three
      cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that
      more patients receiving BEV-CT than CT would achieve at least a 15% (>= 15-point)
      absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36)
      at week 8/9. Patients with missing week 8/9 questionnaires were included as
      unimproved. Questionnaires from all assessments until disease progression were
      analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity
      analyses were used to determine the effects of differing assumptions and methods
      for missing data. RESULTS: Baseline questionnaires were available from 89% of 361
      randomly assigned patients. More BEV-CT than CT patients achieved a >= 15%
      improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v
      9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering
      all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6;
      P = .015). More BEV-CT than CT patients achieved >= 15% improvement in FOSI at
      week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003).
      Sensitivity analyses gave similar results and conclusions. CONCLUSION:
      Bevacizumab increased the proportion of patients achieving a 15% improvement in
      patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant
      ovarian cancer.

PMID- 24687830
TI  - Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk
      factor for lapatinib-induced liver injury.
AB  - PURPOSE: Liver injury is a serious adverse event leading to permanent
      discontinuation of lapatinib in affected patients. This study aimed to validate
      previously associated major histocompatibility complex (MHC) variants as
      predictors of risk of liver injury by using a large, randomized, placebo
      controlled trial of lapatinib in human epidermal growth factor receptor 2
      positive, early-stage breast cancer (Tykerb Evaluation After Chemotherapy
      [TEACH]: Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer).
      PATIENTS AND METHODS: The frequency of ALT elevation cases was compared among
      four MHC variants in 1,194 patients randomly assigned to lapatinib. Cumulative
      ALT elevation time courses during treatment were also compared between carriers
      and noncarriers of specified MHC variants. RESULTS: In lapatinib-treated
      patients, there was a significant difference in ALT case incidence between HLA
      carriers and noncarriers. The highly correlated alleles HLA-DRB1*07:01 and HLA
      DQA1*02:01 (study frequency, 22.4%) were associated with ALT elevation (odds
      ratio, 14) between cases (n = 37) and controls (n = 1,071). These associations
      strengthened at higher ALT elevation thresholds and in Hy's Law cases. In
      lapatinib-treated patients, the overall risk for National Cancer Institute-Common
      Terminology Criteria for Adverse Events grade 3 ALT elevation (> 5* upper limit
      of normal) was 2.1%; HLA allele carriers had an increased risk of 7.7%; in
      noncarriers, risk was reduced to 0.5%, comparable to ALT elevation for all
      patients receiving placebo. The increase in ALT case incidence in the lapatinib
      arm showed no evidence of plateau during 1 year of lapatinib treatment.
      CONCLUSION: These results validate HLA-DRB1*07:01 allele carriage as a predictor
      of increased risk of lapatinib-induced liver injury and implicate an immune
      pathology. The HLA association could support clinical management of patients
      experiencing hepatotoxicity during lapatinib treatment.

PMID- 24687831
TI  - t(14;18) Translocation: A predictive blood biomarker for follicular lymphoma.
AB  - PURPOSE: The (14;18) translocation constitutes both a genetic hallmark and
      critical early event in the natural history of follicular lymphoma (FL). However,
      t(14;18) is also detectable in the blood of otherwise healthy persons, and its
      relationship with progression to disease remains unclear. Here we sought to
      determine whether t(14;18)-positive cells in healthy individuals represent tumor
      precursors and whether their detection could be used as an early predictor for
      FL. PARTICIPANTS AND METHODS: Among 520,000 healthy participants enrolled onto
      the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort,
      we identified 100 who developed FL 2 to 161 months after enrollment.
      Prediagnostic blood from these and 218 controls were screened for t(14;18) using
      sensitive polymerase chain reaction-based assays. Results were subsequently
      validated in an independent cohort (65 case participants; 128 controls). Clonal
      relationships between t(14;18) cells and FL were also assessed by molecular
      backtracking of paired prediagnostic blood and tumor samples. RESULTS: Clonal
      analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples
      demonstrated that progression to FL occurred from t(14;18)-positive committed
      precursors. Furthermore, healthy participants at enrollment who developed FL up
      to 15 years later showed a markedly higher t(14;18) prevalence and frequency than
      controls (P < .001). Altogether, we estimated a 23-fold higher risk of subsequent
      FL in blood samples associated with a frequency > 10(-4) (odds ratio, 23.17; 95%
      CI, 9.98 to 67.31; P < .001). Remarkably, risk estimates remained high and
      significant up to 15 years before diagnosis. CONCLUSION: High t(14;18) frequency
      in blood from healthy individuals defines the first predictive biomarker for FL,
      effective years before diagnosis.

PMID- 24687832
TI  - A major step forward for BRCA1/2-related cancer risk management.

PMID- 24687833
TI  - PEAK: a randomized, multicenter phase II study of panitumumab plus modified
      fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6
      in patients with previously untreated, unresectable, wild-type KRAS exon 2
      metastatic colorectal cancer.
AB  - PURPOSE: To evaluate panitumumab plus modified fluorouracil, leucovorin, and
      oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously
      untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal
      cancer (mCRC). A prespecified secondary objective was to assess treatment effects
      in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS.
      PATIENTS AND METHODS: Patients with WT KRAS exon 2 tumors were randomly assigned
      at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6.
      The primary end point was progression-free survival (PFS); secondary end points
      included overall survival (OS) and safety. RESULTS: Of 285 randomly assigned
      patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group,
      PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P =
      .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab
      arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS
      subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm
      (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months
      (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab
      arms, respectively. Treatment discontinuation rates because of adverse events
      were similar between arms. CONCLUSION: PFS was similar and OS was improved with
      panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with
      WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more
      clinical benefit with anti-epidermal growth factor receptor therapy.

PMID- 24687834
TI  - Providing high-quality and affordable intensive care to patients with cancer: The
      forgotten brick in the steep wall of costs throughout the cancer care continuum.

PMID- 24687835
TI  - Providing high-quality and affordable intensive care to patients with cancer: The
      forgotten brick in the steep wall of costs throughout the cancer care continuum.
      Reply to M. Soares et al.

PMID- 24687836
TI  - Impact on survival and toxicity by duration of weight extremes during treatment
      for pediatric acute lymphoblastic leukemia: A report from the Children's Oncology
      Group.
AB  - PURPOSE: Previous studies regarding the influence of weight on event-free
      survival (EFS) and treatment-related toxicity (TRT) in childhood acute
      lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as
      weight varies substantially over treatment, we hypothesized its impact on EFS is
      instead determined by cumulative time spent at an extreme weight during therapy
      and on TRT by weight at the time of toxicity. PATIENTS AND METHODS: In a cohort
      of 2,008 children treated for high-risk ALL in Children's Oncology Group study
      CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at
      an extreme weight (either obese or underweight) between end of induction and
      start of maintenance therapy. We also evaluated the association between weight
      category and incidence and patterns of TRT during 13,946 treatment courses.
      RESULTS: Being obese or underweight at diagnosis and for >= 50% of the time
      between end of induction and start of maintenance therapy resulted in inferior
      EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization
      of weight during that period resulted in mitigation of this risk comparable to
      never being obese or underweight. Obese or underweight status at start of each
      treatment course was significantly associated with specific patterns of TRT.
      CONCLUSION: Influence of weight extremes on EFS and TRT is not set at diagnosis
      as previously reported but is moderated by subsequent weight status during
      intensive postinduction treatment phases. These observations suggest that weight
      is a potentially addressable risk factor to improve EFS and morbidity in
      pediatric ALL.

PMID- 24687837
TI  - Confirmation of the mantle-cell lymphoma International Prognostic Index in
      randomized trials of the European Mantle-Cell Lymphoma Network.
AB  - PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with
      poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was
      developed as the first prognostic stratification tool specifically directed to
      patients with MCL. External validation was planned to be performed on the cohort
      of the two recently completed randomized trials of the European MCL Network.
      PATIENTS AND METHODS: Data of 958 patients with MCL (median age, 65 years; range,
      32 to 87 years) treated upfront in the trials MCL Younger or MCL Elderly were
      pooled to assess the prognostic value of MIPI with respect to overall survival
      (OS) and time to treatment failure (TTF). RESULTS: Five-year OS rates in MIPI
      low, intermediate, and high-risk groups were 83%, 63%, and 34%, respectively. The
      hazard ratios for OS of intermediate versus low and high versus intermediate risk
      patients were 2.1 (95% CI, 1.5 to 2.9) and 2.6 (2.0 to 3.3), respectively. MIPI
      was similarly prognostic for TTF. All four clinical baseline characteristics
      constituting the MIPI, age, performance status, lactate dehydrogenase level, and
      WBC count, were confirmed as independent prognostic factors for OS and TTF. The
      validity of MIPI was independent of trial cohort and treatment strategy.
      CONCLUSION: MIPI was prospectively validated in a large MCL patient cohort
      homogenously treated according to recognized standards. As reflected in current
      guidelines, MIPI represents a generally applicable prognostic tool to be used in
      research as well as in clinical routine, and it can help to develop risk-adapted
      treatment strategies to further improve clinical outcome in MCL.

PMID- 24687838
TI  - How to interpret patient preferences in selecting the best drug: are the current
      measurements up to the job?

PMID- 24687839
TI  - Primary CNS CCND1/MYC-Positive Double-Hit B-Cell Lymphoma: A Case Report and
      Review of the Literature.

PMID- 24687840
TI  - Liquid diet induces memory impairment accompanied by a decreased number of
      hippocampal neurons in mice.
AB  - It is suggested that masticatory dysfunction affects the central nervous system;
      however, the underlying mechanism remains unknown. Brain-derived neurotrophic
      factor (BDNF) and its receptor, TrkB, are known to play important roles in memory
      and learning. In this study, we examined the effects of mastication on memory,
      the expression levels of BDNF and TrkB, and the number of neurons in the
      hippocampus of mice. Male C57 BL/6J mice (3 weeks old) were randomly divided into
      the control group (N = 7) fed chow pellets and the experimental group (N = 7) fed
      a liquid diet, which reduces mastication during eating. At 14 weeks of age, we
      performed a passive avoidance test and found that memory and learning ability
      were impaired in the experimental group compared with the control group. After
      the behavioral experiment, brains were harvested and analyzed morphologically and
      biochemically. In the hippocampus of the experimental group, the expression
      levels of BDNF were significantly higher, whereas those of TrkB were lower than
      those of the control group. In the cerebral cortex, these levels remained
      unchanged between the two groups. The ratio of phospho-p44/42 ERK/pan ERK, a
      downstream molecule of BDNF/TrkB signaling, in the experimental group was
      significantly lower than that of the control group in the cortex and hippocampus.
      The number of pyramidal neurons in the hippocampus was lower in the experimental
      group than in the control group. These findings suggest that reduced mastication
      induced by a liquid diet in early childhood may impair memory and learning
      ability, accompanied by neuronal loss in the hippocampus.

PMID- 24687841
TI  - Estrogen deficiency does not decrease the in vitro osteogenic potential of rat
      adipose-derived mesenchymal stem cells.
AB  - Osteoporosis due to estrogen deficiency is an increasing bone health issue
      worldwide: new strategies are being studied for regenerative medicine of bone
      pathologies in these patients. The most commonly used cells for tissue
      engineering therapy are the bone marrow mesenchymal stem cells (BMSCs), but they
      might be negatively affected by aging and estrogen deficiency. Besides the
      general advantages of adipose-derived mesenchymal stem cells (ADSCs) over BMSCs,
      ADSCs also seem to be less affected by aging than BMSCs, but in the literature,
      little is known about ADSCs in estrogen deficiency. The present study
      investigated the in vitro behavior of ADSCs, isolated from healthy (SHAM) and
      estrogen-deficient (OVX) rats. Phenotype, clonogenicity, viability, and
      osteogenic differentiation, at both cellular and molecular levels, were evaluated
      with or without osteogenic stimuli. Pro-inflammatory cytokines, growth factors,
      and adipogenic differentiation markers were also analyzed. There were no
      significant differences between OVX and SHAM ADSCs in some analyzed parameters.
      In addition, clonogenicity, osteopontin (Spp1) gene expression, alkaline
      phosphatase (ALP) activity at 2 weeks of culture, total collagen (COLL),
      osteocalcin (Bglap) gene expression and production, and matrix mineralization
      were significantly higher in OVX than in SHAM ADSCs. Besides the increase in some
      osteogenic markers, peroxisome proliferator-activated receptor gamma (Pparg) gene
      was also more expressed in OVX in osteogenic medium, with a concomitant estrogen
      receptor 1 (Esr1) gene expression decrease. These results underlined that ADSCs
      were not affected by estrogen deficiency in an osteogenic microenvironment.

PMID- 24687842
TI  - Ratio of gamma-H2AX level in lymphocytes to that in granulocytes detected using
      flow cytometry as a potential biodosimeter for radiation exposure.
AB  - This study aims to assess utilisation of the ratio of gamma-H2AX in lymphocytes
      to that in granulocytes (RL/G of gamma-H2AX) in blood as a rapid method for
      population triage and dose estimation during large-scale radiation emergencies.
      Blood samples from healthy volunteers exposed to 0-10 Gy of (60)Co irradiation
      were collected. The samples were cultured for 0-24 h and then analysed using flow
      cytometry to measure the levels of gamma-H2AX in lymphocytes and granulocytes.
      The basal RL/G levels of gamma-H2AX in healthy human blood, the response of RL/G
      of gamma-H2AX to ionising radiation and its relationship with doses, time
      intervals after exposure and individual differences were also analysed. The level
      of gamma-H2AX in lymphocytes increased in a dose-dependent manner after
      irradiation, whereas the level in granulocytes was not affected. A linear dose
      effect relationship with low inter-experimental and inter-individual variations
      was observed. The RL/G of gamma-H2AX may be used as a biomarker for population
      triage and dose estimation during large-scale radiation emergencies if blood
      samples can be collected within 24 h.

PMID- 24687843
TI  - Constructing and validating readability models: the method of integrating
      multilevel linguistic features with machine learning.
AB  - Multilevel linguistic features have been proposed for discourse analysis, but
      there have been few applications of multilevel linguistic features to readability
      models and also few validations of such models. Most traditional readability
      formulae are based on generalized linear models (GLMs; e.g., discriminant
      analysis and multiple regression), but these models have to comply with certain
      statistical assumptions about data properties and include all of the data in
      formulae construction without pruning the outliers in advance. The use of such
      readability formulae tends to produce a low text classification accuracy, while
      using a support vector machine (SVM) in machine learning can enhance the
      classification outcome. The present study constructed readability models by
      integrating multilevel linguistic features with SVM, which is more appropriate
      for text classification. Taking the Chinese language as an example, this study
      developed 31 linguistic features as the predicting variables at the word,
      semantic, syntax, and cohesion levels, with grade levels of texts as the
      criterion variable. The study compared four types of readability models by
      integrating unilevel and multilevel linguistic features with GLMs and an SVM. The
      results indicate that adopting a multilevel approach in readability analysis
      provides a better representation of the complexities of both texts and the
      reading comprehension process. 

PMID- 24687844
TI  - Pisotriquetral joint disorders: an under-recognized cause of ulnar side wrist
      pain.
AB  - Pisotriquetral joint disorders are often under-recognized in routine clinical
      practice. They nevertheless represent a significant cause of ulnar side wrist
      pain. The aim of this article is to present the main disorders of this joint and
      discuss the different imaging modalities that can be useful for its assessment. 

PMID- 24687845
TI  - Exploring cartilage damage in gout using 3-T MRI: distribution and associations
      with joint inflammation and tophus deposition.
AB  - OBJECTIVE: Few imaging studies have investigated cartilage in gout. Magnetic
      resonance imaging (MRI) can image cartilage damage and also reveals other
      features of gouty arthropathy. The objective was to develop and validate a system
      for quantifying cartilage damage in gout. METHODS: 3-T MRI scans of the wrist
      were obtained in 40 gout patients. MRI cartilage damage was quantified using an
      adaptation of the radiographic Sharp van der Heijde score. Two readers scored
      cartilage loss at 7 wrist joints: 0 (normal), 1 (partial narrowing), 2 (complete
      narrowing) and concomitant osteoarthritis was recorded. Bone erosion, bone oedema
      and synovitis were scored (RAMRIS) and tophi were assessed. Correlations between
      radiographic and MRI cartilage scores were investigated, as was the reliability
      of the MRI cartilage score and its associations. RESULTS: The GOut MRI Cartilage
      Score (GOMRICS) was highly correlated with the total Sharp van der Heijde (SvdH)
      score and the joint space narrowing component (R = 0.8 and 0.71 respectively, p <
      0.001). Reliability was high (intraobserver, interobserver ICCs = 0.87 [0.57
      0.97], 0.64 [0.41-0.79] respectively), and improved on unenhanced scans;
      interobserver ICC = 0.82 [0.49-0.95]. Cartilage damage was predominantly focal
      (82% of lesions) and identified in 40 out of 280 (14%) of joints. Cartilage
      scores correlated with bone erosion (R = 0.57), tophus size (R = 0.52), and
      synovitis (R = 0.55), but not bone oedema scores. CONCLUSIONS: Magnetic resonance
      imaging can be used to investigate cartilage in gout. Cartilage damage was
      relatively uncommon, focal, and associated with bone erosions, tophi and
      synovitis, but not bone oedema. This emphasises the unique pathophysiology of
      gout.

PMID- 24687846
TI  - Support for the Multidimensional Adolescent Stress Questionnaire in a Sample of
      Adolescents in the United Kingdom.
AB  - Adolescence is a time of physical, social and emotional development, and this
      development can be accompanied by feelings of stress. The Adolescent Stress
      Questionnaire is a 56-item scale measuring stress in 10 domains. Developed in
      Australia, the scale has been translated, and its reliability and validity have
      been tested in a number of countries across Europe, where the 10-factor, 56-item
      version of the scale has received little support. The present study tested the
      factor structure, construct validity and reliability in a sample (n = 610) of
      adolescents in the United Kingdom. Support was found for the 10-factor, 56-item
      version of the scale, and correlations with self-concept measures, sex scores on
      stress factors and Cronbach's alpha-values, suggesting that the scale may be a
      viable assessment tool for adolescent stress. Results for alcohol-specific
      analyses support the domain-specific nature of the scale. Future work may seek to
      investigate the stability of age-specific stress domains (e.g. the stress of
      Emerging Adult Responsibility) in samples that include younger adolescents.

PMID- 24687847
TI  - A pathway linking patient participation in cancer consultations to pain control.
AB  - OBJECTIVE: To test a pathway through which a tailored, pain management education
      coaching intervention could contribute to better cancer pain control through the
      effects of patients' communication about pain on physician prescribing of pain
      medication. METHODS: Secondary analysis of data from a randomized controlled
      trial that tested the effects of a tailored education-coaching intervention on
      pain control for patients with advanced cancer. The current analysis focused on a
      subset of the patients (n = 135) who agreed to have their consultations audio
      recorded. Patients' active communication about pain (e.g., expressing questions,
      concerns, and preferences about pain-related issues) was coded from audio
      recordings. Change in pain medication was measured by patient self-report.
      Improvement in pain control was scored as the difference between baseline pain
      score and pain reported at 6 weeks. RESULTS: Patients' pain-related communication
      was a significant predictor of patient-reported changes in physician prescribing
      of pain medication (p < .0001) and mediated the effect of baseline pain on
      medication change. Other predictors of change in pain medication were age
      (younger) and having participated in the intervention (as opposed to usual care).
      Of the patients reporting adjustment in pain medications, 49% experienced better
      pain control compared with only 27% of patients reporting no change in pain
      management (p < .02). CONCLUSIONS: Cancer patients who ask questions, express
      concerns, and state preferences about pain-related matters can prompt physicians
      to change their pain management regimen, which in turn may lead to better pain
      control. Future research should model pathways through which clinician-patient
      communication can lead to better cancer outcomes.

PMID- 24687848
TI  - Treating parents with attention-deficit/hyperactivity disorder: the effects of
      behavioral parent training and acute stimulant medication treatment on parent
      child interactions.
AB  - This multiple baseline study evaluated the efficacy of behavioral parent training
      (BPT) for 12 parents (M age = 39.17 years; 91% mothers) and their children (ages
      6-12; 83% boys) both with Attention-Deficit/Hyperactivity Disorder (ADHD), and
      also explored the acute effect of stimulant medication for parents before and
      after BPT. Parents rated their own and their children's symptoms and impairment
      and were stabilized on optimally dosed medication. Then, parents discontinued
      medication and were randomly assigned to a 3, 4, or 5 week baseline (BL), during
      which they provided twice-weekly ratings of their impairment, parenting, and
      their child's behavior. Following BL, parents and their children completed two
      laboratory tasks, once on their optimally dosed medication and once on a placebo
      to assess observable effects of medication on parent-child behavior, and they
      completed additional assessments of family functioning. Parents then completed
      eight BPT sessions, during which they were unmedicated. Twice-weekly ratings of
      parent and child behavior were collected during BPT and additional ratings were
      collected upon completing BPT. Two more parent-child tasks with and without
      parent medication were conducted upon BPT completion to assess the observable
      effects of BPT and BPT plus medication. Ten (83.33%) parents completed the trial.
      Improvements in parent and child behavior were observed, and parents reported
      improved child behavior with BPT. Few benefits of BPT emerged through parent
      reports of parent functioning, with the exception of inconsistent discipline, and
      no medication or interaction effects emerged. These results, although
      preliminary, suggest that some parents with ADHD benefit from BPT. While
      pharmacological treatment is the most common intervention for adults with ADHD,
      further examination of psychosocial treatments for adults is needed.

PMID- 24687849
TI  - KAP1 represses differentiation-inducible genes in embryonic stem cells through
      cooperative binding with PRC1 and derepresses pluripotency-associated genes.
AB  - Embryonic stem (ES) cells express pluripotency-associated genes and repress
      differentiation-inducible genes. The activities of these genes are coordinately
      reversed during differentiation. The changes in the transcriptome upon
      conditional KAP1 knockout in ES cells overlapped with the changes during embryoid
      body formation. KAP1 repressed differentiation-inducible genes and derepressed
      pluripotency-associated genes in ES cells. KAP1 formed complexes with polycomb
      repressive complexes 1 (PRC1) through an interaction that was mediated by the
      KAP1 coiled-coil region. KAP1 and PRC1 bound cooperatively at the promoters of
      differentiation-inducible genes and repressed their transcription. In contrast,
      KAP1 bound the transcribed and flanking sequences of pluripotency-associated
      genes, did not enhance PRC1 binding, and derepressed their transcription. KAP1
      had opposite effects on differentiation-inducible and pluripotency-associated
      gene transcription both in ES cells and in differentiating embryoid bodies. The
      region of KAP1 that mediated the interaction with PRC1 was required for KAP1
      enhancement of PRC1 binding and for KAP1 repression of transcription at
      differentiation-inducible promoters. This region of KAP1 was not required for
      KAP1 suppression of PRC1 binding or for KAP1 derepression of transcription at
      pluripotency-associated promoters. The opposite effects of KAP1 on the
      transcription of differentiation-inducible versus pluripotency-associated genes
      contributed to the reciprocal changes in their transcription during
      differentiation. 

PMID- 24687850
TI  - H2A.Z-dependent regulation of cohesin dynamics on chromosome arms.
AB  - Structural maintenance of chromosomes (SMC) complexes and DNA topoisomerases are
      major determinants of chromosome structure and dynamics. The cohesin complex
      embraces sister chromatids throughout interphase, but during mitosis most cohesin
      is stripped from chromosome arms by early prophase, while the remaining cohesin
      at kinetochores is cleaved at anaphase. This two-step removal of cohesin is
      required for sister chromatids to separate. The cohesin-related Smc5/6 complex
      has been studied mostly as a determinant of DNA repair via homologous
      recombination. However, chromosome segregation fails in Smc5/6 null mutants or
      cells treated with small interfering RNAs. This also occurs in Smc5/6 hypomorphs
      in the fission yeast Schizosaccharomyces pombe following genotoxic and
      replication stress, or topoisomerase II dysfunction, and these mitotic defects
      are due to the postanaphase retention of cohesin on chromosome arms. Here we show
      that mitotic and repair roles for Smc5/6 are genetically separable in S. pombe.
      Further, we identified the histone variant H2A.Z as a critical factor to modulate
      cohesin dynamics, and cells lacking H2A.Z suppress the mitotic defects conferred
      by Smc5/6 dysfunction. Together, H2A.Z and the SMC complexes ensure genome
      integrity through accurate chromosome segregation. 

PMID- 24687851
TI  - USP28 is recruited to sites of DNA damage by the tandem BRCT domains of 53BP1 but
      plays a minor role in double-strand break metabolism.
AB  - The DNA damage response (DDR) is critical for genome stability and the
      suppression of a wide variety of human malignancies, including neurodevelopmental
      disorders, immunodeficiency, and cancer. In addition, the efficacy of many
      chemotherapeutic strategies is dictated by the status of the DDR. Ubiquitin
      specific protease 28 (USP28) was reported to govern the stability of multiple
      factors that are critical for diverse aspects of the DDR. Here, we examined the
      effects of USP28 depletion on the DDR in cells and in vivo. We found that USP28
      is recruited to double-strand breaks in a manner that requires the tandem BRCT
      domains of the DDR protein 53BP1. However, we observed only minor DDR defects in
      USP28-depleted cells, and mice lacking USP28 showed normal longevity,
      immunological development, and radiation responses. Our results thus indicate
      that USP28 is not a critical factor in double-strand break metabolism and is
      unlikely to be an attractive target for therapeutic intervention aimed at
      chemotherapy sensitization. 

PMID- 24687852
TI  - Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein
      interactions mediated by its C-terminal WD40 domain.
AB  - Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are associated with
      familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that
      consists of multiple domains, including predicted C-terminal WD40 repeats. In
      this study, we analyzed functional and molecular features conferred by the WD40
      domain. Electron microscopic analysis of the purified LRRK2 C-terminal domain
      revealed doughnut-shaped particles, providing experimental evidence for its WD40
      fold. We demonstrate that LRRK2 WD40 binds and sequesters synaptic vesicles via
      interaction with vesicle-associated proteins. In fact, a domain-based pulldown
      approach combined with mass spectrometric analysis identified LRRK2 as being part
      of a highly specific protein network involved in synaptic vesicle trafficking. In
      addition, we found that a C-terminal sequence variant associated with an
      increased risk of developing PD, G2385R, correlates with a reduced binding
      affinity of LRRK2 WD40 to synaptic vesicles. Our data demonstrate a critical role
      of the WD40 domain within LRRK2 function. 

PMID- 24687853
TI  - p19Ink4d is a tumor suppressor and controls pituitary anterior lobe cell
      proliferation.
AB  - Pituitary tumors develop in about one-quarter of the population, and most arise
      from the anterior lobe (AL). The pituitary gland is particularly sensitive to
      genetic alteration of genes involved in the cyclin-dependent kinase (CDK)
      inhibitor (CKI)-CDK-retinoblastoma protein (Rb) pathway. Mice heterozygous for
      the Rb mutation develop pituitary tumors, with about 20% arising from the AL.
      Perplexingly, none of the CKI-deficient mice reported thus far develop pituitary
      AL tumors. In this study, we show that deletion of p19(Ink4d) (p19), a CKI gene,
      in mice results in spontaneous development of tumors in multiple organs and
      tissues. Specifically, more than one-half of the mutant mice developed pituitary
      hyperplasia or tumors predominantly in the AL. Tumor development is associated
      with increased cell proliferation and enhanced activity of Cdk4 and Cdk6 and
      phosphorylation of Rb protein. Though Cdk4 is indispensable for postnatal
      pituitary cell proliferation, it is not required for the hyperproliferative
      pituitary phenotype caused by p19 loss. Loss of p19 phosphorylates Rb in Cdk4(-/
      ) pituitary AL cells and mouse embryonic fibroblasts (MEFs) and rescues their
      proliferation defects, at least partially, through the activation of Cdk6. These
      results provide the first genetic evidence that p19 is a tumor suppressor and the
      major CKI gene that controls pituitary AL cell proliferation. 

PMID- 24687854
TI  - Transcript stabilization by the RNA-binding protein HuR is regulated by cellular
      retinoic acid-binding protein 2.
AB  - The RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target
      transcripts, thereby protecting them against degradation. We show that HuR
      directly interacts with cellular retinoic acid-binding protein 2 (CRABP2), a
      protein known to transport RA from the cytosol to the nuclear retinoic acid
      receptor (RAR). Association with CRABP2 dramatically increases the affinity of
      HuR toward target mRNAs and enhances the stability of such transcripts, including
      that of Apaf-1, the major protein in the apoptosome. We show further that its
      cooperation with HuR contributes to the ability of CRABP2 to suppress carcinoma
      cell proliferation. The data show that CRABP2 displays antioncogenic activities
      both by cooperating with RAR and by stabilizing antiproliferative HuR target
      transcripts. The observation that CRABP2 controls mRNA stabilization by HuR
      reveals that in parallel to participating in transcriptional regulation, the
      protein is closely involved in posttranscriptional regulation of gene expression.

PMID- 24687856
TI  - A novel transcript, VNN1-AB, as a biomarker for colorectal cancer.
AB  - Colorectal cancer is a global health challenge with high incidence rate and
      mortality. The patients' prognosis is strongly associated with disease stage and
      currently there is a need for improved prognostic and predictive biomarkers. In
      this study, novel colorectal cancer-specific transcript structures were nominated
      from whole transcriptome sequencing of seven colorectal cancer cell lines, two
      primary colorectal carcinomas with corresponding normal colonic mucosa and 16
      normal tissues. The nominated transcripts were combined with gene level outlier
      expression analyses in a cohort of 505 colorectal cancers to identify biomarkers
      with capacity to stratify colorectal cancer subgroups. The transcriptome
      sequencing data and outlier expression analysis revealed 11 novel colorectal
      cancer-specific exon-exon junctions, of which 3 were located in the gene VNN1.
      The junctions within VNN1 were further characterized using rapid amplification of
      cDNA ends (RACE) and the prevalence of the subsequently characterized novel
      transcript, VNN1-AB, was investigated by real-time RT-PCR in 291 samples of
      miscellaneous origins. VNN1-AB was not present in any of the 43 normal colorectal
      tissue samples investigated, but in 5 of the 6 polyps, and 102 of the 136 (75%)
      colorectal cancers. We have identified a novel transcript of the VNN1 gene, with
      an organ-confined complete specificity for colorectal neoplasia. 

PMID- 24687855
TI  - Unraveling the complexities of DNA-dependent protein kinase autophosphorylation.
AB  - DNA-dependent protein kinase (DNA-PK) orchestrates DNA repair by regulating
      access to breaks through autophosphorylations within two clusters of sites (ABCDE
      and PQR). Blocking ABCDE phosphorylation (by alanine mutation) imparts a dominant
      negative effect, rendering cells hypersensitive to agents that cause DNA double
      strand breaks. Here, a mutational approach is used to address the mechanistic
      basis of this dominant negative effect. Blocking ABCDE phosphorylation
      hypersensitizes cells to most types of DNA damage (base damage, cross-links,
      breaks, and damage induced by replication stress), suggesting that DNA-PK binds
      DNA ends that result from many DNA lesions and that blocking ABCDE
      phosphorylation sequesters these DNA ends from other repair pathways. This
      dominant negative effect requires DNA-PK's catalytic activity, as well as
      phosphorylation of multiple (non-ABCDE) DNA-PK catalytic subunit (DNA-PKcs)
      sites. PSIPRED analysis indicates that the ABCDE sites are located in the only
      contiguous extended region of this huge protein that is predicted to be
      disordered, suggesting a regulatory role(s) and perhaps explaining the large
      impact ABCDE phosphorylation has on the enzyme's function. Moreover, additional
      sites in this disordered region contribute to the ABCDE cluster. These data,
      coupled with recent structural data, suggest a model whereby early
      phosphorylations promote initiation of nonhomologous end joining (NHEJ), whereas
      ABCDE phosphorylations, potentially located in a "hinge" region between the two
      domains, lead to regulated conformational changes that initially promote NHEJ and
      eventually disengage NHEJ. 

PMID- 24687857
TI  - Zwitterionic-coated "stealth" nanoparticles for biomedical applications: recent
      advances in countering biomolecular corona formation and uptake by the
      mononuclear phagocyte system.
AB  - Nanoparticles represent highly promising platforms for the development of imaging
      and therapeutic agents, including those that can either be detected via more than
      one imaging technique (multi-modal imaging agents) or used for both diagnosis and
      therapy (theranostics). A major obstacle to their medical application and
      translation to the clinic, however, is the fact that many accumulate in the liver
      and spleen as a result of opsonization and scavenging by the mononuclear
      phagocyte system. This focused review summarizes recent efforts to develop
      zwitterionic-coatings to counter this issue and render nanoparticles more
      biocompatible. Such coatings have been found to greatly reduce the rate and/or
      extent of non-specific adsorption of proteins and lipids to the nanoparticle
      surface, thereby inhibiting production of the "biomolecular corona" that is
      proposed to be a universal feature of nanoparticles within a biological
      environment. Additionally, in vivo studies have demonstrated that larger-sized
      nanoparticles with a zwitterionic coating have extended circulatory lifetimes,
      while those with hydrodynamic diameters of <=5 nm exhibit small-molecule-like
      pharmacokinetics, remaining sufficiently small to pass through the fenestrae and
      slit pores during glomerular filtration within the kidneys, and enabling
      efficient excretion via the urine. The larger particles represent ideal
      candidates for use as blood pool imaging agents, whilst the small ones provide a
      highly promising platform for the future development of theranostics with reduced
      side effect profiles and superior dose delivery and image contrast capabilities. 

PMID- 24687858
TI  - Complete genome sequence and comparative analysis of grass carp reovirus strain
      109 (GCReV-109) with other grass carp reovirus strains reveals no significant
      correlation with regional distribution.
AB  - A new grass carp reovirus strain, tentatively named GCReV-109, was isolated in
      Hubei, China, and its complete genome sequence was determined. The genome
      contained 11 double-stranded RNA segments (S1-S11) covering 24,620 base pairs.
      All of the segments had conserved terminal nucleotides, with GUAA(U)/CU at the 5'
      end and UCAUC at the 3' end. Protein sequence comparison showed that GCReV-109
      was most closely related to GCRV-GD108 and shared 96.6-99.5 % protein sequence
      identity but only shared 16.7-46.1 and 15.1-45.4 % identity with GCRV-873 and
      HGDRV, respectively. Phylogenetic analysis showed that grass carp reovirus
      strains in China can be divided into three genotypes. Further analysis revealed
      homology between the GCRV-109 VP56 and HGDRV VP55 proteins, as well as GCReV-109
      NS38, GCRV-873 NS38, and HGDRV VP39. The results of these comparisons also
      indicated that the homology between viruses was not necessarily linked to their
      geographical distribution. Our study will help in recognizing and understanding
      the genome structure and genetic diversity of grass carp reovirus. 

PMID- 24687859
TI  - Mixed infection of Sida jamaicensis in Jamaica reveals the presence of three
      recombinant begomovirus DNA A components.
AB  - Begomoviruses impose serious constraints on agriculture throughout the temperate,
      tropical and subtropical regions. Previously, we characterised a sida golden
      yellow vein virus isolate, SiGYVV-[JM:Lig2:08] (HQ009519-20) from a symptomatic
      Sida jamaicensis plant. With the aim of establishing whether it was hosting a
      mixed infection that could facilitate recombination, PCR-RFLP was done on DNA
      extracted from this plant, and the results suggested the presence of two
      additional genetically distinct DNA-A molecules. Sequence analysis of these two
      DNA-A molecules (relying on BLAST searches and the CLUSTAL V algorithm within the
      DNASTAR MegAlign module) revealed that they belonged to novel species, and we
      have tentatively named these viruses sida golden mosaic Braco virus
      [Jamaica:Liguanea:2008] and sida golden mosaic Liguanea virus-[Jamaica:1:2008].
      Using RDP4 (recombination detection program), we determined that all three
      viruses were recombinant, with bases ~10 to ~440 of both SiGMLigV-[JM:Lig:08] and
      SiGYVV-[JM:Lig2:08] having been derived from a relative of SiGMBV-[JM:Lig:08]
      (P<2.070*10(-7) for all seven of the recombination detection methods). SiGMBV
      [JM:Lig:08] was itself a product of recombination, deriving bases ~490-1195 from
      a virus that was ~92% similar to malvastrum yellow mosaic Helshire virus.
      Phylogenetically, these DNA-A components are most closely related to those of
      malvaceous weed-infecting begomoviruses from Jamaica, Cuba, Florida and Mexico.
      The SiGMBV DNA-A was able to elicit symptomatic infection in N. benthamiana.

PMID- 24687860
TI  - Synchrotron-based X-ray-sensitive nanoprobes for cellular imaging.
AB  - It is one of the ultimate goals in cell biology to understand the complex spatio
      temporal interplay of biomolecules in the cellular context. To this end, there
      have been great efforts on the development of various probes to detect and
      localize specific biomolecules in cells with a variety of microscopic imaging
      techniques. In this Research News, we first summarize several types of microscopy
      for visualizing specific biomolecular targets. Then we focus on recent advances
      in the design of X-ray sensitive nanoprobes for applications in synchrotron-based
      cellular imaging. With the availability of advanced synchrotron techniques, there
      has been rapid progress toward high-resolution and multi-color X-ray imaging in
      cells with various types of functional nanoprobes. 

PMID- 24687861
TI  - tert-Butyl hydroperoxide-induced differing plasma membrane and oxidative stress
      processes in yeast strains BY4741 and erg5Delta.
AB  - The molecular mechanism of tert-butyl hydroperoxide (t-BuOOH) elicited
      cytotoxicity and the background of t-BuOOH sensitivity were studied in the
      Saccharomyces cerevisiae ergosterol-less gene deletion mutant erg5Delta and its
      parental strain BY4741. In comparison to BY4741, untreated erg5Delta cells
      exhibited alterations in sterol and fatty acid compositions of the plasma
      membrane, as reflected by the inherent amphotericin B resistance, an elevated
      level (31%) of plasma membrane rigidity and a decreased uptake of glycerol.
      Surprisingly, the untreated erg5Delta cells exhibited an unbalanced intracellular
      redox state, accompanied by the continuous upregulation of the antioxidant
      enzymes Mn superoxide dismutase, catalase, and glutathione S-transferase, which
      resulted in decreased specific concentrations of superoxide and peroxides and
      elevated levels of the hydroxyl radical and thiols. The 2.5-fold sensitivity of
      erg5Delta to t-BuOOH suggested that the oxidative stress adaptation processes of
      the mutant could not restore the redox homeostasis of the cells and there is an
      overlap between sterol and redox homeostases. t-BuOOH treatment of both strains
      induced adaptive modification of the sterol and fatty acid compositions,
      increased the plasma membrane fluidity and elevated the specific activities of
      most antioxidant enzymes through specific regulation processes in a strain
      dependent manner. 

PMID- 24687862
TI  - Fibronectin enhances spinal cord astrocyte proliferation by elevating P2Y1
      receptor expression.
AB  - After spinal cord injury (SCI), the formation of glial scar is a complex process
      that is attributed primarily to astrocytic proliferation, but the mechanism of
      astrocytes proliferation is still unclear. Fibronectin is a large extracellular
      glycoprotein that helps organize the matrix protein, and its main membrane
      receptor is the alpha5 beta1 integrin subunit. In this study, fibronectin
      stimulated spinal cord astrocytic proliferation from two directions: fibronectin
      increased astrocytic proliferation via alpha5 beta1 integrin receptor, and
      fibronectin upregulated the expression of P2Y1 receptor, and adenosine
      triphosphate (ATP) could enhance the astrocytic proliferation and induce more
      release of arachidonic acid and prostaglandin E2 via P2Y1. The upregulation of
      P2Y1 by fibronectin required [Ca2+]i and the activation of integrin link kinase
      (ILK) and Akt. We found that [Ca2+]i stimulated by fibronectin was alpha5 beta1
      integrin receptor dependent and that the phosphorylation of Akt or extracellular
      signal-regulated protein kinase (ERK1/2) induced by fibronectin mediated the
      activation of cAMP response element-binding protein (CREB) and signal transducer
      and activator of transcription 3 (Stat3). Our research suggests that the release
      of fibronectin and ATP could stimulate the spinal cord astrocytic proliferation
      after SCI, and the expression of P2Y1 increased by fibronectin would provide more
      sites for ATP, which could aggravate the proliferation and inflammation of spinal
      cord astrocytes.

PMID- 24687863
TI  - The mechanism of the one-step synthesis of hollow-structured Li(3)VO(4) as an
      anode for lithium-ion batteries.
AB  - In recent years, the controlled synthesis of inorganic micro- and nanostructures
      with hollow interiors has attracted considerable attention because of their
      widespread potential applications. A feasible method for synthesizing Li3 VO4 by
      a template-free, solution synthesis of single-crystalline microboxes with well
      defined non-spherical morphologies has been reported. This study provides the
      useful information to produce other hollow structure materials to the broad
      audience of readers. The formation of hollow structure and the influence of raw
      materials have been presented. The thus-synthesized Li3 VO4 exhibited
      significantly improved conductivity, rate capability, and cycling life compared
      to commercial graphite, synthesized Li4 Ti5 O12 , and previously reported Li3 VO4
      . 

PMID- 24687864
TI  - Neuronal RNA-binding proteins in health and disease.
AB  - In mammalian cells in general and in neurons in particular, mRNA maturation,
      translation, and degradation are highly complex and dynamic processes. RNA
      binding proteins (RBPs) play crucial roles in all these events. First, they
      participate in the choice of pre-mRNA splice sites and in the selection of the
      polyadenylation sites, determining which of the possible isoforms is produced
      from a given precursor mRNA. Then, once in the cytoplasm, the protein composition
      of the RNP particles determines whether the mature mRNA is transported along the
      dendrites or the axon of a neuron to the synapses, how efficiently it is
      translated, and how stable it is. In agreement with their importance for neuronal
      function, mutations in genes that code for RBPs are associated with various
      neurological diseases. In this review, we illustrate how individual RBPs
      determine the fate of an mRNA, and we discuss how mutations in RBPs or
      perturbations of the mRNA metabolism can cause neurodegenerative disorders.

PMID- 24687865
TI  - Trends of weekly musculoskeletal pain from 2000 to 2012: National study of
      Finnish university students.
AB  - BACKGROUND: There are no nationwide trend surveys of the prevalence of
      musculoskeletal symptoms among university students. The aim of the study was to
      examine whether the prevalence of perceived musculoskeletal pain symptoms among
      Finnish university students has changed from 2000 to 2012, and to explore the co
      occurrence of these symptoms. METHODS: Four cross-sectional nationwide
      representative samples (n = 11,502) were compared in 2000 (n = 3174), 2004 (n =
      3153), 2008 (n = 2750) and 2012 (n = 2425). The prevalence of weekly neck
      shoulder, lower back, limb or joint, and temporomandibular joint pain was
      studied. RESULTS: All the studied pains increased significantly from 2000 to
      2012. The prevalence rate of neck-shoulder pain increased from 25% to 29%, lower
      back pain from 10% to 14%, and limb and joint pain increased from 7% to 8%. The
      prevalence of pain in temporomandibular joint increased from 4% to 5%. In
      addition, the co-occurrence of different musculoskeletal pain symptoms increased.
      All of these pain symptoms were more common among female students and among older
      students. CONCLUSION: An increasing trend in the prevalence of frequent
      musculoskeletal pain was found over the period of 12-years among Finnish
      university students.

PMID- 24687867
TI  - Pancreatic enzyme replacement therapy during pancreatic insufficiency.
AB  - Pancreatic stimulation and therefore digestion is a tightly controlled and
      hormonally mediated process. Any alterations affecting any of the systematic
      steps for successful digestion and absorption to occur will impair appropriate
      pancreatic enzymatic secretion, entry into the bowel lumen, functionality once
      inside the lumen, and thus appropriate mixing with foods and nutrients. Many
      causes of pancreatic insufficiency may require the initiation of pancreatic
      enzyme therapy, including but not limited to cystic fibrosis, pancreatic cancer,
      acute and chronic pancreatitis, and pancreatic surgery. This purpose of this
      article is to help clarify the conditions that cause pancreatic insufficiency,
      how to determine if the patient is malabsorbing, and the best use of pancreatic
      enzyme replacement therapy for treatment in these conditions. The first step in
      determining if pancreatic enzyme therapy is appropriate is to determine if the
      patient is malabsorbing specifically due to pancreatic exocrine insufficiency. An
      overview of the methods used to determine pancreatic insufficiency is provided,
      as well as appropriate treatment methods. Recent Food and Drug Administration
      regulations require a more thorough process, including randomized controlled
      trials to prove the safety and efficacy of pancreatic enzymes, to approve them
      for use. The studies used to verify efficacy also are examined. Last, dosing
      guidelines and some unconventional ways to administer pancreatic enzymes, such as
      during enteral feedings, are reviewed. 

PMID- 24687866
TI  - Potential influence of intravenous lipids on the outcomes of acute pancreatitis.
AB  - Parenteral nutrition (PN) has been associated with a higher rate of adverse
      outcomes compared with enteral feeding in patients with acute pancreatitis (AP).
      However, PN may be necessary when feeding via the enteral route is poorly
      tolerated or impossible, and PN is recommended as a second-line nutrition therapy
      in AP. Intravenous (IV) lipids are commonly used as a part of PN in patients with
      AP. While the adverse outcomes related to the use of PN in AP have commonly been
      attributed to infectious complications, data suggest that the unsaturated fatty
      acids in the triglycerides used in IV lipids may contribute to the development of
      organ failure. We discuss the clinical and experimental data on this issue and
      the alternative lipid emulsions that are being studied. 

PMID- 24687868
TI  - Application of quantitative 1H-NMR method to determination of gentiopicroside in
      Gentianae radix and Gentianae scabrae radix.
AB  - A quantitative (1)H-NMR method (qHNMR) was used to measure gentiopicroside
      content in Gentianae radix and Gentianae scabrae radix. Gentiopicroside is a
      major component of Gentianae radix and Gentianae scabrae radix. The purity of
      gentiopicroside was calculated from the ratio of the intensity of the H-3 signal
      at delta 7.44 ppm or the H-8 signal at delta 5.78 ppm in methanol-d 4 of
      gentiopicroside to that of a hexamethyldisilane (HMD) signal at 0 ppm. The
      concentration of HMD was corrected with SI traceability by using potassium
      hydrogen phthalate of certified reference material (CRM) grade. As a result, the
      gentiopicroside content in two lots of Gentianae radix as determined by qHNMR was
      found to be 1.76 and 2.17 %, respectively. The gentiopicroside content in two
      lots of Gentianae scabrae radix was 2.73 and 3.99 %, respectively. We
      demonstrated that this method is useful for the quantitative analysis of crude
      drugs. 

PMID- 24687869
TI  - Postmortem CT compared to autopsy in children; concordance in a forensic setting.
AB  - OBJECTIVES: The aim of this study is to assess the accuracy of postmortem CT
      (PMCT) in determining the cause of death in children who underwent a forensic
      autopsy because of a suspected nonnatural death. METHODS: We selected forensic
      pediatric autopsies at the Netherlands Forensic Institute, whereby the subject
      underwent PMCT between 1-1-2008 and 31-12-2012. Cause of death was independently
      scored by a radiologist and a pathologist. Cause of death was classified (1) in
      categories being natural, unnatural, and unknown; (2) according to the ICD-10;
      and (3) according to institutional classification. RESULTS: In the study period,
      189 pediatric forensic autopsies were performed. Fifteen were excluded because of
      putrefaction. Of the remaining 174 autopsies, 98 (56%) underwent PMCT. PMCT and
      autopsy identified the same category in 69/98 cases (70%, kappa 0.49). They
      identified the same cause of death in 66/98 cases (67%, kappa 0.5) using ICD-10;
      in 71/98 (72%, kappa 0.62) using a forensic classification. PMCT performed better
      in unnatural deaths (59-67 % agreement) than in natural deaths (0 % agreement).
      If no cause of death was detected with autopsy, PMCT failed to identify a cause
      of death in 98% (39/40). CONCLUSIONS: Pediatric PMCT does identify the majority
      of unnatural causes of death, but does not identify new diagnoses (true
      positives) if no cause of death is found during autopsy. Diagnostic accuracy in
      natural deaths is low. KEY POINTS: * The case mix is an important predictor for
      the concordance between PMCT and autopsy. * In case of an unnatural death, 72-
      81% of PMCT results matches autopsy results. * In case of a natural death, 0% of
      PMCT results matches autopsy results. * If no cause of death is identified with
      autopsy, 98% of PMCT results concurs.

PMID- 24687872
TI  - Mechanisms of graphene growth on metal surfaces: theoretical perspectives.
AB  - Graphene is an important material with unique electronic properties. Aiming to
      obtain high quality samples at a large scale, graphene growth on metal surfaces
      has been widely studied. An important topic in these studies is the atomic scale
      growth mechanism, which is the precondition for a rational optimization of growth
      conditions. Theoretical studies have provided useful insights for understanding
      graphene growth mechanisms, which are reviewed in this article. On the mostly
      used Cu substrate, graphene growth is found to be more complicated than a simple
      adsorption-dehydrogenation-growth model. Growth on Ni surface is precipitation
      dominated. On surfaces with a large lattice mismatch to graphene, epitaxial
      geometry determin a robust nonlinear growth behavior. Further progresses in
      understanding graphene growth mechanisms is expected with intense theoretical
      studies using advanced simulation techniques, which will make a guided design of
      growth protocols practical. 

PMID- 24687871
TI  - Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine
      approaches and model acquired resistance.
AB  - BACKGROUND: Precision (Personalized) medicine has the potential to revolutionize
      patient health care especially for many cancers where the fundamental disease
      etiology remains either elusive or has no available therapy. Here we outline a
      study in alveolar rhabdomyosarcoma, in which we use gene expression profiling and
      a series of drug prediction algorithms combined with a matched patient-derived
      xenograft (PDX) model to test bioinformatically predicted therapies. PROCEDURE: A
      PDX model was developed from a patient biopsy and a number of drugs identified
      using gene expression analysis in combination with drug prediction algorithms.
      Drugs chosen from each of the predictive methodologies, along with the patient's
      standard-of-care therapy (ICE-T), were tested in vivo in the PDX tumor. A second
      study was initiated using the tumors that re-grew following the ICE-T treatment.
      Further expression analysis identified additional therapies with potential anti
      tumor efficacy. RESULTS: A number of the predicted therapies were found to be
      active against the tumors in particular BGJ398 (FGFR2) and ICE-T. Re-transplanted
      ICE-T treated tumorgrafts demonstrated a decreased response to ICE-T
      recapitulating the patient's refractory disease. Gene expression profiling of the
      ICE-T treated tumorgrafts identified cytarabine (SLC29A1) as a potential therapy,
      which was shown, along with BGJ398, to be highly active in vivo. CONCLUSIONS:
      This study illustrates that PDX models are suitable surrogates for testing
      potential therapeutic strategies based on gene expression analysis, modeling
      clinical drug resistance and hold the potential to assist in guiding prospective
      patient care.

PMID- 24687870
TI  - Applying imaging genetics to ADHD: the promises and the challenges.
AB  - Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent
      childhood psychiatric disorders. During the past decades, studies have focused on
      its genetic background and the abnormality of the brain structure and function.
      Recently, an advanced technique linking these two areas, namely, the imaging
      genetics emerged and kept growing. Imaging genetics primarily identifies genes
      that influence the brain variations. There are three main strategies of doing an
      imaging genetic study: using neuroimaging as endophenotypes to find the
      associated DNA variants, finding neuroimaging effects of risk genes, and
      hypothesis-free whole-brain voxelwise genome-wide association study. In this
      review, we begin with demonstrating the basic principles of imaging genetics
      precisely, with examples from other psychiatric conditions, and then go on to
      synthesize the existing imaging genetic studies in ADHD. Finally, we elaborate
      the challenges of applying imaging genetics to ADHD. We conclude that imaging
      genetics has somewhat showed its potential to provide a more precise
      understanding of how the genes shape the brain variations and further the
      clinical features of ADHD. 

PMID- 24687873
TI  - Enantiomeric separation of indoxacarb on an amylose-based chiral stationary phase
      and its application in study of indoxacarb degradation in water.
AB  - Direct semipreparative enantioseparation of indoxacarb was performed on a
      semipreparative Chiralpak IA column using normal-phase high-performance liquid
      chromatography (HPLC) with n-hexane-isopropanol-ethyl acetate (70:20:10) mixture
      as mobile phase. Degradation of indoxacarb (2.33S + 1R) and its two enantiopure
      isoforms in three aqueous buffer solutions and four water samples collected from
      natural water sources was then elucidated by HPLC analysis on Chiralpak IA
      column. Degradation of all three indoxacarbs complied with first-order kinetics
      and demonstrated linearity with regression coefficients R(2) > n0.88. Indoxacarb
      (2.33S + 1R) underwent enantioselective degradation in river water, rain water,
      and buffer solution of pH 7.0. Enantiopure S-(+)-indoxacarb and R-(-)-indoxacarb
      were both found to be configurationally stable in water.

PMID- 24687874
TI  - Developmental origins and functions of stromal cells in the normal and diseased
      mammalian kidney.
AB  - The kidney is a model developmental paradigm of vertebrate organogenesis. As in
      many other organs, kidney development involves reciprocal inductive tissue
      interactions between multiple cell lineages. The most well defined of these
      interactions occurs between the ureteric bud and the nephrogenic mesenchyme. A
      population of mesenchymal cells distinct from nephrogenic precursors and termed
      stromal cells, have been relatively understudied. Yet existing knowledge
      indicates that stromal cells are critical regulators in the normal and diseased
      kidney. This commentary reviews current knowledge regarding the origin and
      functional roles of the stromal cell population during kidney development. Gaps
      in our current understanding of renal stromal cells and future directions needed
      to advance this expanding field of study are highlighted.

PMID- 24687875
TI  - Enhanced electron injection into inverted polymer light-emitting diodes by
      combined solution-processed zinc oxide/polyethylenimine interlayers.
AB  - Inverted device architectures for organic light-emitting diodes (OLEDs) require
      suitable interfaces or buffer layers to enhance electron injection from highwork
      function transparent electrodes. A solution-processable combination of ZnO and
      PEI is reported, that facilitates electron injection and enables efficient and
      air-stable inverted devices. Replacing the metal anode by highly conductive
      polymers enables transparent OLEDs. 

PMID- 24687877
TI  - Maternal non-Mendelian inheritance of a reduced lifespan? A hypothesis.
AB  - PURPOSE: A negative correlation exists between advanced maternal age and
      reproduction. Current data suggest that this correlation is due to a decline in
      oocyte quality with respect to female age. Since a new individual is derived from
      the fusion of a single sperm and egg, we tested whether the quality of this
      material could influence the long-term physiological health of offspring, by
      examining whether a link between parental age and lifespan of offspring exists.
      METHODS: We requested a search from the Swedish demographic database POPUM 3
      maintained by the University of Umea, Sweden between years 1700 and 1900.
      Parameters requested included mothers' and fathers' age at gestation, the
      lifespan of the children, cause of death of children and the region of birth.
      RESULTS: Complete data was obtained for 30,512 children born to 12,725 mothers
      and fathers. Kaplan-Meier estimators demonstrated a strong relationship between
      mother's age at gestation and the longevity of offspring. Extrinsic factors such
      as century of birth also had an effect on the data. The forward stepwise
      procedure on Cox's model of proportional hazards suggested that most significant
      intrinsic factors were mother's lifespan and mother's age at gestation.
      CONCLUSIONS: These data demonstrate that intrinsic and extrinsic factors
      influence the lifespan of children. Among intrinsic factors, mother's lifespan
      and age at gestation had a significant influence on the data. The influence of
      intrinsic factors remained significant despite a strong extrinsic influence. We
      suggest that the influence of the mother on the lifespan of offspring is due to
      extra-genomic factors.

PMID- 24687879
TI  - [Importance of diagnosis and treatment in chronic migraine].

PMID- 24687876
TI  - Kv7.2 regulates the function of peripheral sensory neurons.
AB  - The Kv7 (KCNQ) family of voltage-gated K(+) channels regulates cellular
      excitability. The functional role of Kv7.2 has been hampered by the lack of a
      viable Kcnq2-null animal model. In this study, we generated homozygous Kcnq2-null
      sensory neurons using the Cre-Lox system; in these mice, Kv7.2 expression is
      absent in the peripheral sensory neurons, whereas the expression of other
      molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is
      not altered. The conditional Kcnq2-null animals exhibit normal motor performance
      but have increased thermal hyperalgesia and mechanical allodynia. Whole-cell
      patch recording technique demonstrates that Kcnq2-null sensory neurons have
      increased excitability and reduced spike frequency adaptation. Taken together,
      our results suggest that the loss of Kv7.2 activity increases the excitability of
      primary sensory neurons.

PMID- 24687880
TI  - [What is the optimal dose for the prophylactic treatment of chronic migraine
      patients?].
AB  - INTRODUCTION: OnabotulinumtoxinA (OnabotA) is indicated for headache prophylaxis
      in patients with chronic migraine. However, there is some controversy about what
      is the minimum effective dose for treating chronic migraine patients. AIM: To
      determine the optimal dose of OnabotA for the prophylactic treatment of patients
      with chronic migraine. DEVELOPMENT: We performed a literature review of the
      randomized, double blind, placebo-controlled studies that have evaluated the
      safety and efficacy of OnabotA as headache prophylactic treatment in migraine
      patients. In the studies conducted before the PREEMPT clinical programme, a
      variety of dose ranges and infiltration paradigms were used. Initial phase II
      studies of OnabotA in chronic daily headache showed that those patients treated
      with 150 U had significant mean reductions from baseline in headache frequency
      compared with placebo, and this benefit was not observed for patients treated
      with 75 U. The experience from previous studies allowed to define an injection
      paradigm and dose range (155-195 U) that was used in the PREEMPT clinical trials.
      PREEMPT studies demonstrate that OnabotA is a safe an effective prophylactic
      treatment for chronic migraine. CONCLUSIONS: Available evidence to date supports
      that the optimal dose for the treatment of chronic migraine patients is the use
      of at least 150 U of OnabotA, that should be administered according to the
      PREEMPT injection paradigm.

PMID- 24687878
TI  - Syncytin-1 and its receptor is present in human gametes.
AB  - MAIN PURPOSE AND RESEARCH QUESTION: To determine whether the true fusogen
      Syncytin-1 and its receptor (ASCT-2) is present in human gametes using qRT-PCR,
      immunoblotting and immunofluorescence. METHODS: Donated oocytes and spermatozoa,
      originating from a fertility center in tertiary referral university hospital,
      underwent qRT-PCR, immunoblotting and immunofluorescence analyzes. RESULTS:
      Quantitative RT-PCR of sperm samples from sperm donors showed that syncytin-1 is
      present in all samples, however, protein levels varied between donors. Syncytin-1
      immunoreactivity predominates in the sperm head and around the equatorial
      segment. The receptor ASCT-2 is expressed in the acrosomal region and in the
      sperm tail. Moreover, ASCT-2, but not syncytin-1, is expressed in oocytes and the
      mRNA level increases with increasing maturity of the oocytes. CONCLUSIONS:
      Syncytin and its receptor are present in human gametes and localization and
      temporal appearance is consistent with a possible role in fusion between oocyte
      and sperm.

PMID- 24687881
TI  - [What benefits does the preventive treatment of migraine have?].
AB  - The preventive treatment of migraine is under-used. Moreover, treatment
      compliance and persistence rates are low. Yet, it is crucial to be able to
      control the frequency, intensity and duration of the attacks of migraine, which
      enables patients to resort to painkillers less often. All this plays a key role
      in improving the associated quality of life and disability. It is important to
      have a clear idea of the goals of preventive treatment, as well as the
      indications for starting it, its ideal duration and compliance. Enhancing and
      completing the knowledge we have about preventive treatment will probably improve
      its prescription and provide tools that allow an increase in patient compliance
      to be achieved. 

PMID- 24687882
TI  - [The myth of tension-type headache].
AB  - Tension-type headache is an entity recognised by the International Headache
      Society in its International Headache Classification. The limits of this
      condition, however, are somewhat fuzzy and poorly defined, and its diagnostic
      criteria are a sort of negation of the symptoms of migraine. In this review we
      are especially interested in highlighting the diagnostic vagueness in patients
      with chronic tension-type headache. This refers, above all, to those with a clear
      history of migraine and who continue to suffer a number of crises with symptoms
      of migraine, although they have headaches with tension-type features on a daily
      basis. Emphasis will be placed on the novel concept of chronic migraine which,
      today, can include these patients, and has not only diagnostic but also, and
      above all, therapeutic implications. Tension-type headache is a clinical syndrome
      that probably covers a series of entities with important aetiopathogenic
      differences from one to another and, perhaps sometime in the future, many
      patients who are now labelled as having been diagnosed with this condition will
      be classified further as having other better-defined diseases. In any case,
      although it might sound like a myth or just pie-in-the-sky, the tension-type
      headache is still needed to encompass these entities that are lacking any better
      defined diagnoses. 

PMID- 24687883
TI  - [OnabotulinumtoxinA in chronic migraine: from the theory of clinical trials to
      clinical practice].
AB  - The introduction of OnabotulinumtoxinA (OnabotA) in the treatment of chronic
      migraine has brought with it a significant change in the management of these
      patients. Its novel mechanism of action, the fact that it is administered as an
      injection and the need to repeat treatment and control regimens all suggest the
      need to modify the therapeutic strategy applied in this clinical situation. This
      article briefly reviews the main clinical evidence on the effectiveness of
      OnabotA in chronic migraine based on the clinical trials conducted to date. At
      the same time it also performs a critical analysis of the application of OnabotA
      in daily clinical practice. It includes the findings of a survey carried out on
      Spanish neurologists about their experience in the application of OnabotA in
      patients with chronic migraine in order to determine the real situation in our
      milieu. The main conclusions include the need to use suitable doses of OnabotA,
      together with appropriate injection points, the non-exclusion of patients with
      very frequent crises, concomitant preventive treatment or medication abuse,
      waiting up to 15 days in order to be able to observe the clinical effectiveness
      and not considering OnabotA as ineffective until after having performed 2-3
      infiltration regimens. 

PMID- 24687884
TI  - Uniform Mesoporous Anatase Hollow Spheres: An Unexpectedly Efficient Fabrication
      Process and Enhanced Performance in Photocatalytic Hydrogen Evolution.
AB  - Uniform mesoporous anatase hollow spheres with high crystallinity have been
      fabricated by an efficient method, in which biocompatible ethanedioic acid acts
      as the chelating agent during the Ostwald ripening process. The combination of
      high crystallinity, large surface area, and mesoporosity leads to an excellent
      photocatalytic activity. In solar water splitting, the hollow spheres exhibit
      remarkably enhanced photocatalytic performance that is 1.4 times of P25.

PMID- 24687885
TI  - Development of novel PET probe [11C](R,R)HAPT and its stereoisomer [11C](S,S)HAPT
      for vesicular acetylcholine transporter imaging: a PET study in conscious monkey.
AB  - Carbon-11-labeled (R,R)trans-8-methyl-2-hydroxy-3-[4-[2-aminophenyl]piperizinyl]
      tetralin ([(11)C](R,R)HAPT) and its stereoisomer [(11)C](S,S)HAPT were developed
      for imaging vesicular acetylcholine transporters (VAChTs), exclusively located in
      presynaptic cholinergic neurons. Both positron emission tomography (PET) probes
      were evaluated in the brain of conscious monkey (Macaca mulatta) using high
      resolution PET. Time-activity curves (TACs) of [(11)C](R,R)HAPT peaked within 5
      min after the injection in all regions except the caudate and putamen, both of
      which showed peaks around 20 min postinjection. The regional distribution
      patterns of [(11)C](R,R)HAPT determined as total distribution volume (V(t)) were
      highest in the putamen, high in the caudate, intermediate in the amygdala,
      hippocampus, and thalamus, lower in the cingulate gyrus and frontal, temporal,
      and occipital cortices, and lowest in the cerebellum. In contrast, the
      distribution and TACs of [(11)C](S,S)HAPT were homogeneous in all regions. The
      uptake of [(11)C](R,R)HAPT was reduced by 1 mg/kg (-)-vesamicol, a specific VAChT
      antagonist, in all regions except the cerebellum, but not by 0.1 mg/kg SA4503, a
      specific sigma-1 receptor agonist. These results well reflect the in vitro
      affinity assessments using rat cerebral membranes. They also demonstrate that
      [(11)C](R,R)HAPT is a potential PET probe for noninvasive and quantitative
      imaging of VAChT in the living brain.

PMID- 24687886
TI  - Insula and sensory insular cortex and somatosensory control in patients with
      insular stroke.
AB  - BACKGROUND: In functional imaging studies, the insular cortex (IC) has been
      identified as an essential part of the processing of a whole spectrum of
      multimodal sensory input. However, there are no lesion studies including a
      sufficient number of patients, which would reinforce the functional imaging data
      obtained from healthy subjects. Such lesion studies should examine how damage to
      the IC affects sensory perception. We chose acute stroke patients with lesions
      affecting the IC in order to fill this gap. METHODS: A comprehensive sensory
      profiling by applying a quantitative sensory testing protocol was performed and a
      voxel-lesion behaviour mapping analysis in 24 patients with acute unilateral
      cortical damage was applied. RESULTS: Our data demonstrate that patients with
      lesions of the posterior IC have deficits in temperature perception, but did not
      show other sensory deficits such as hot or cold pain perception associated with
      specific lesion locations. CONCLUSION: Our data allow the conclusion that the
      posterior IC may represent the major region responsible for encoding warm and
      cold perception in the brain. To what extent focal IC lesions may also impair
      pain processing or induce post-stroke pain has to be addressed in future studies
      including more patients.

PMID- 24687887
TI  - Follicular lymphoma: 2014 update on diagnosis and management.
AB  - DISEASE OVERVIEW: Follicular lymphoma is generally an indolent B cell
      lymphoproliferative disorder of transformed follicular center B cells. Follicular
      lymphoma (FL) is characterized by diffuse lymphoadenopathy, bone marrow
      involvement, splenomegaly, and less commonly other extranodal sites of
      involvement. In general cytopenias can occur but constitutional symptoms of
      fever, nightsweats, and weight loss are uncommon. DIAGNOSIS: Diagnosis is based
      on histology of preferably a biopsy of a lymph node. Immunohistochemical staining
      is positive in virtually all cases for cell surface CD19, CD20, CD10, and
      monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein.
      The overwhelming majority of cases have the characteristic t(14;18) translocation
      involving the IgH/bcl-2 genes. RISK STRATIFICATION: The Follicular Lymphoma
      International Prognostic Index prognostic model for FL uses five independent
      predictors of inferior survival: age >60 years, hemoglobin <12 g/dL, serum LDH >
      normal, Ann Arbor stage III/IV, number of involved nodal areas > 4. The presence
      of 0, 1, 2, and  >= 3 adverse factors defines low, intermediate, and high-risk
      disease. With the use of more modern therapies, outcomes have improved. RISK
      ADAPTED THERAPY: Observation continues to be adequate for asymptomatic patients
      with low bulk disease and no cytopenias. For patients needing therapy, most
      patients are treated with chemotherapy plus rituximab, which has improved
      response rates, duration of response and overall survival. Randomized studies
      have shown additional benefit for maintenance rituximab both following
      chemotherapy-rituximab and single agent rituximab. Experimental therapies as well
      as stem cell transplantation (SCT) are considered for recurrent disease.

PMID- 24687888
TI  - Discovery of colorectal cancer biomarker candidates by membrane proteomic
      analysis and subsequent verification using selected reaction monitoring (SRM) and
      tissue microarray (TMA) analysis.
AB  - Recent advances in quantitative proteomic technology have enabled the large-scale
      validation of biomarkers. We here performed a quantitative proteomic analysis of
      membrane fractions from colorectal cancer tissue to discover biomarker
      candidates, and then extensively validated the candidate proteins identified. A
      total of 5566 proteins were identified in six tissue samples, each of which was
      obtained from polyps and cancer with and without metastasis. GO cellular
      component analysis predicted that 3087 of these proteins were membrane proteins,
      whereas TMHMM algorithm predicted that 1567 proteins had a transmembrane domain.
      Differences were observed in the expression of 159 membrane proteins and 55
      extracellular proteins between polyps and cancer without metastasis, while the
      expression of 32 membrane proteins and 17 extracellular proteins differed between
      cancer with and without metastasis. A total of 105 of these biomarker candidates
      were quantitated using selected (or multiple) reaction monitoring (SRM/MRM) with
      stable synthetic isotope-labeled peptides as an internal control. The results
      obtained revealed differences in the expression of 69 of these proteins, and this
      was subsequently verified in an independent set of patient samples (polyps (n =
      10), cancer without metastasis (n = 10), cancer with metastasis (n = 10)).
      Significant differences were observed in the expression of 44 of these proteins,
      including ITGA5, GPRC5A, PDGFRB, and TFRC, which have already been shown to be
      overexpressed in colorectal cancer, as well as proteins with unknown function,
      such as C8orf55. The expression of C8orf55 was also shown to be high not only in
      colorectal cancer, but also in several cancer tissues using a multicancer tissue
      microarray, which included 1150 cores from 14 cancer tissues. This is the largest
      verification study of biomarker candidate membrane proteins to date; our methods
      for biomarker discovery and subsequent validation using SRM/MRM will contribute
      to the identification of useful biomarker candidates for various cancers. Data
      are available via ProteomeXchange with identifier PXD000851. 

PMID- 24687889
TI  - Histopathological spectrum of bone lesions associated with dental implant
      failure: osteomyelitis and beyond.
AB  - Early or late post-implant placement complications are usually localized
      infectious/inflammatory processes and treated accordingly. If the healing process
      does not take place within a reasonable timeframe, the possibility of a
      pathologic process beyond localized infection/inflammation should be suspected.
      We describe a radiological/histopathological spectrum of bony lesions ranging
      from inflammatory to malignant lesions surrounding failed dental implants. Five
      cases of mandibular dental implant failure that clinically, radiologically and
      histopathologically appeared to be inflammatory processes are presented. The
      failure of the dental implants was immediate in two cases and late in the
      remaining three. The radiological features were essentially similar for all five,
      and they included radiolucent or mixed radiolucent-radiopaque lesions with poorly
      defined borders. Three lesions were limited to the area of the failed implant,
      while the other two extended to a large part of the mandible. The
      histopathological findings ranged from acute osteomyelitis and chronic
      osteomyelitis with features of a fibro-osseous-like lesion and occasional rimming
      of atypical osteoblasts to osteogenic sarcoma that was admixed with a component
      of osteomyelitis (diagnosis of the latter was achieved only after a series of
      biopsies). In-depth investigative procedures are imperative in order to establish
      an accurate diagnosis whenever the histopathological diagnosis is inconsistent
      with persisting clinical signs and symptoms in bone lesions associated with
      failed dental implants. 

PMID- 24687890
TI  - PETRORISK: a risk assessment framework for petroleum substances.
AB  - PETRORISK is a modeling framework used to evaluate environmental risk of
      petroleum substances and human exposure through these routes due to emissions
      under typical use conditions as required by the European regulation for the
      Registration, Evaluation, Authorization and Restriction of Chemicals (REACH).
      Petroleum substances are often complex substances comprised of hundreds to
      thousands of individual hydrocarbons. The physicochemical, fate, and effects
      properties of the individual constituents within a petroleum substance can vary
      over several orders of magnitude, complicating risk assessment. PETRORISK
      combines the risk assessment strategies used on single chemicals with the
      hydrocarbon block approach to model complex substances. Blocks are usually
      defined by available analytical characterization data on substances that are
      expressed in terms of mass fractions for different structural chemical classes
      that are specified as a function of C number or boiling point range. The
      physicochemical and degradation properties of the blocks are determined by the
      properties of representative constituents in that block. Emissions and predicted
      exposure concentrations (PEC) are then modeled using mass-weighted individual
      representative constituents. Overall risk for various environmental compartments
      at the regional and local level is evaluated by comparing the PECs for individual
      representative constituents to corresponding predicted no-effect concentrations
      (PNEC) derived using the Target Lipid Model. Risks to human health are evaluated
      using the overall predicted human dose resulting from multimedia environmental
      exposure to a substance-specific derived no-effect level (DNEL). A case study is
      provided to illustrate how this modeling approach has been applied to assess the
      risks of kerosene manufacture and use as a fuel.

PMID- 24687891
TI  - Parkinson's disease: recent advances.
AB  - While a curative treatment for Parkinson's disease remains elusive, our
      understanding of disease mechanisms as well as preclinical and pre-motor early
      manifestations has improved greatly over the past years. An agent with proven
      disease modifying properties has not yet been identified but symptomatic
      treatment options for affected patients have improved. For patients with motor
      complications, this includes invasive approaches such as deep brain stimulation
      and continuous device-aided drug delivery. The many facets of non-motor problems
      patients are faced with have finally been fully recognized and have become the
      target of treatment trials, as have been non-pharmacological approaches.

PMID- 24687892
TI  - Motivational modulation of bradykinesia in Parkinson's disease off and on
      dopaminergic medication.
AB  - Motivational influence on bradykinesia in Parkinson's disease may be observed in
      situations of emotional and physical stress, a phenomenon known as paradoxical
      kinesis. However, little is known about motivational modulation of movement speed
      beyond these extreme circumstances. In particular, it is not known if
      motivational factors affect movement speed by improving movement
      preparation/initiation or execution (or both) and how this effect relates to the
      patients' medication state. In the present study, we tested if provision of
      motivational incentive through monetary reward would speed-up movement initiation
      and/or execution in Parkinson's disease patients and if this effect depended on
      dopaminergic medication. We studied the effect of monetary incentive on simple
      reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic
      medication and in 11 healthy participants. The simple reaction time task was
      performed across unrewarded and rewarded blocks. The initiation time and movement
      time were quantified separately. Anticipation errors and long responses were also
      recorded. The prospect of reward improved initiation times in Parkinson's disease
      patients both "off" and "on" dopaminergic medication, to a similar extent as in
      healthy participants. However, for "off" medication, this improvement was
      associated with increased frequency of anticipation errors, which were eliminated
      by dopamine replacement. Dopamine replacement had an additional, albeit small
      effect, on reward-related improvement of movement execution. Motivational
      strategies are helpful in overcoming bradykinesia in Parkinson's disease.
      Motivational factors may have a greater effect on bradykinesia when patients are
      "on" medication, as dopamine appears to be required for overcoming speed-accuracy
      trade-off and for improvement of movement execution. Thus, medication status
      should be an important consideration in movement rehabilitation programmes for
      patients with Parkinson's disease. 

PMID- 24687893
TI  - Patterns of decline in upper limb function of boys and men with DMD: an
      international survey.
AB  - With increasing life expectancy, upper extremity (UE) function becomes more and
      more important in boys with Duchenne muscular dystrophy (DMD). Knowledge of UE
      function in these children is, however, limited. The aim of this study was to
      gain insight into the changing patterns of UE function during the course of DMD.
      A Web-based questionnaire on UE function, covering all domains of the
      International Classification of Functioning Disability and Health, was
      distributed worldwide. Primary domains of the questionnaire were: participant
      characteristics, UE pain and stiffness, UE activities, and social participation.
      Data were described per disease stage and analyzed using descriptive analysis. A
      total of 213 boys/men with DMD (1-35 years) were included in this study. UE pain,
      stiffness, and activity limitations increased with disease stage. UE activity
      limitations already occurred in the early ambulatory stage. Compared to the
      healthy population, social participation was restricted in DMD patients and about
      70% of the respondents experienced UE limitations when performing social
      activities. Despite the existence of UE impairments, only 9% of the respondents
      used supportive aids. Functional capacities and activities of the UE are limited
      already in the early ambulatory stage of patients with DMD affecting their social
      participation. Therefore, clinicians should pay attention to UE limitations
      before DMD patients lose their capacity to walk. Effective and adequate aids as
      well as attention for pain and stiffness in the therapeutic management could help
      to reduce UE activity limitations and related restrictions in social
      participation.

PMID- 24687894
TI  - Autonomic symptoms in idiopathic REM behavior disorder: a multicentre case
      control study.
AB  - Patients with idiopathic REM sleep behavior disorder (iRBD) are at very high risk
      of developing neurodegenerative synucleinopathies, which are disorders with
      prominent autonomic dysfunction. Several studies have documented autonomic
      dysfunction in iRBD, but large-scale assessment of autonomic symptoms has never
      been systematically performed. Patients with polysomnography-confirmed iRBD (318
      cases) and controls (137 healthy volunteers and 181 sleep center controls with
      sleep diagnoses other than RBD) were recruited from 13 neurological centers in 10
      countries from 2008 to 2011. A validated scale to study the disorders of the
      autonomic nervous system in Parkinson's disease (PD) patients, the SCOPA-AUT, was
      administered to all the patients and controls. The SCOPA-AUT consists of 25 items
      assessing the following domains: gastrointestinal, urinary, cardiovascular,
      thermoregulatory, pupillomotor, and sexual dysfunction. Our results show that
      compared to control subjects with a similar overall age and sex distribution,
      patients with iRBD experience significantly more problems with gastrointestinal,
      urinary, and cardiovascular functioning. The most prominent differences in
      severity of autonomic symptoms between our iRBD patients and controls emerged in
      the gastrointestinal domain. Interestingly, it has been reported that an altered
      gastrointestinal motility can predate the motor phase of PD. The cardiovascular
      domain SCOPA-AUT score in our study in iRBD patients was intermediate with
      respect to the scores reported in PD patients by other authors. Our findings
      underline the importance of collecting data on autonomic symptoms in iRBD. These
      data may be used in prospective studies for evaluating the risk of developing
      neurodegenerative disorders. 

PMID- 24687895
TI  - Clinical characteristics and functional outcome of patients with West Nile
      neuroinvasive disease in Serbia.
AB  - Neurologic manifestations are prominent characteristic of West Nile virus (WNV)
      infection. The aim of this article was to describe neurological manifestations in
      patients with WNV neuroinvasive disease and their functional outcome at discharge
      in the first human outbreak of WNV infection in Serbia. The study enrolled
      patients treated in the Clinic for Infectious and Tropical Diseases, Clinical
      Center Serbia in Belgrade, with serological evidence of acute WNV infection who
      presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP).
      Functional outcome at discharge was assessed using modified Rankin Scale (mRS)
      and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients
      had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among
      patients with AFP, 12 resembled poliomyelitis and one had clinical and
      electrodiagnostic findings consistent with polyradiculoneuritis. Among patients
      with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight
      (15.4 %) presented with cerebellitis. Respiratory failure with subsequent
      mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %)
      patients died, five (9.6 %) were functionally dependent (mRS 3-5), and 38 (73.1
      %) were functionally independent at discharge (mRS 0-2). In univariate analysis,
      the presence of AFP, respiratory failure and consciousness impairment were found
      to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p <
      0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection
      in Serbia caused a notable case fatality ratio, especially in patients with AFP,
      respiratory failure and consciousness impairment. Rhombencephalitis and
      cerebellitis could be underestimated presentations of WNV neuroinvasive disease.

PMID- 24687896
TI  - An unusual cause of acute paraplegia in a 16-year-old dancer.

PMID- 24687897
TI  - Long-term cognitive outcome of bilateral subthalamic deep brain stimulation in
      Parkinson's disease.
AB  - The effect of subthalamic deep brain stimulation (STN DBS) on cognition in
      Parkinson's disease (PD) remains controversial, and it is unclear which factors
      are related to cognitive decline and dementia after STN DBS, especially over the
      long term. To this end, we analyzed the cognitive outcome of 103 non-demented
      patients with PD who were followed-up for at least 12 months after bilateral STN
      DBS surgery. Preoperatively, the patients were evaluated with the Unified
      Parkinson's Disease Rating Scale and neuropsychological tests. The rate of global
      cognitive decline and the incidence of dementia during follow-up for up to 7
      years (mean 42.4 +/- 24.5 months) were calculated, and preoperative clinical and
      neuropsychological factors associated with postoperative global cognitive decline
      or dementia were analyzed. The prevalence of mild cognitive impairment (MCI) and
      its relation to later cognitive decline or dementia were also evaluated. The
      annual decline in the mini-mental state examination score was 0.4 +/- 1.7 with
      impaired attention and executive function and a higher levodopa equivalent dose
      at baseline being the predictors of a faster global cognitive decline after STN
      DBS. Dementia developed in 13 patients with an incidence rate of 35.7 per 1,000
      person-years. Impaired executive function at baseline predicted dementia. At
      baseline, 63.1 % of the patients had PD-MCI, and these patients were more likely
      to develop dementia than those without PD-MCI. This study showed that
      dysfunctions in the frontostriatal circuitry at baseline were associated with a
      risk of subsequent global cognitive decline and dementia in patients with PD who
      underwent STN DBS. In addition, preoperative PD-MCI was a risk factor for
      dementia after STN DBS.

PMID- 24687898
TI  - A simple brain atrophy measure improves the prediction of malignant middle
      cerebral artery infarction by acute DWI lesion volume.
AB  - In patients with malignant middle cerebral artery infarction (MMI) decompressive
      surgery within 48 h improves functional outcome. In this respect, early
      identification of patients at risk of developing MMI is crucial. While the acute
      diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high
      predictive values, the potential impact of preexisting brain atrophy on the
      course of space-occupying middle cerebral artery (MCA) infarction and the
      development of MMI remains unclear. We tested the hypothesis that the combination
      of the acute DWI lesion volume with simple measures of brain atrophy improves the
      early prediction of MMI. Data from a prospective, multicenter, observational
      study, which included patients with acute middle cerebral artery main stem
      occlusion studied by MRI within 6 h of symptom onset, was analyzed
      retrospectively. The development of MMI was defined according to the European
      randomized controlled trials of decompressive surgery. Acute DWI lesion volume,
      as well as brain and cerebrospinal fluid volume (CSF) were delineated. The
      intercaudate distance (ICD) was assessed as a linear brain atrophy marker by
      measuring the hemi-ICD of the intact hemisphere to account for local brain
      swelling. Binary logistic regression analysis was used to identify significant
      predictors of MMI. Cut-off values were determined by Classification and
      Regression Trees analysis. Sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) of the resulting models were
      calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle
      cerebral artery infarctions patients had higher National Institutes of Health
      Stroke Scale scores on admission and presented more often with combined occlusion
      of the internal carotid artery and MCA. There were no differences in brain and
      CSF volume between the two groups. Diffusion weighted imaging lesion volume was
      larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients.
      Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to
      predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD <= 9.4
      mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93
      vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to
      1/15 (7 %), while there were only slight changes in specificity, sensitivity and
      NPV. The absolute number of correct classifications increased by 4 (3.4 %). The
      integration of hemi-ICD as a linear marker of brain atrophy, that can easily be
      assessed in an emergency setting, may improve the prediction of MMI by lesion
      volume based predictive models.

PMID- 24687899
TI  - Construction of 2D atomic crystals on transition metal surfaces: graphene,
      silicene, and hafnene.
AB  - The synthesis and structures of graphene on Ru(0001) and Pt(111), silicene on
      Ag(111) and Ir(111) and the honeycomb hafnium lattice on Ir(111) are reviewed.
      Epitaxy on a transition metal (TM) substrate is a pro-mising method to produce a
      variety of two dimensional (2D) atomic crystals which potentially can be used in
      next generation electronic devices. This method is particularly valuable in the
      case of producing 2D materials that do not exist in 3D forms, for instance,
      silicene. Based on the intensive investigations of epitaxial graphene on TM in
      recent years, it is known that the quality of graphene is affected by many
      factors, including the interaction between the 2D material overlayer and the
      substrate, the lattice mismatch, the nucleation density at the early stage of
      growth. It is found that these factors also apply to many other epitaxial 2D
      crystals on TM. The knowledge from the reviewed systems will shine light on the
      design and synthesis of new 2D crystals with novel properties. 

PMID- 24687900
TI  - Hox expression in the direct-type developing sand dollar Peronella japonica.
AB  - BACKGROUND: Echinoderms are a curious group of deuterostomes that forms a clade
      with hemichordates but has a pentameral body plan. Hox complex plays a pivotal
      role in axial patterning in bilaterians and often occurs in a cluster on the
      chromosome. In contrast to hemichordates with an organized Hox cluster, the sea
      urchin Strongylocentrotus purpuratus has a Hox cluster with an atypical
      organization. However, the current data on hox expression in sea urchin rudiments
      are fragmentary. RESULTS: We report a comprehensive examination of hox expression
      in a sand dollar echinoid. Nine hox genes are expressed in the adult rudiment,
      which are classified into two groups, but hox11/13b belongs to both: one with
      linear expression in the coelomic mesoderm and another with radial expression
      around the adult mouth. The linear genes may endow the coelom/mesentery with
      axial information to direct postmetamorphic transformation of the digestive
      tract, whereas the radial genes developmentally correlate with the morphological
      novelties of echinoderms and/or sea urchins. Recruitment of the radial genes
      except hox11/13b appears to be accompanied by the loss of ancestral/axial roles.
      CONCLUSIONS: This in toto co-option of the hox genes provides insight into the
      molecular mechanisms underlying the evolution of echinoderms from a bilateral
      ancestor.

PMID- 24687901
TI  - Comparison of prothrombin time derived from CoaguChek XS and laboratory test
      according to fibrinogen level.
AB  - BACKGROUND: CoaguChek XS is one of the most widely used point-of-care (POC)
      devices to evaluate prothrombin time for monitoring oral anticoagulant therapy.
      Unlike laboratory methods, it detects electrical signals produced by thrombin
      activity to derive the international normalized ratio (INR). Therefore, we
      hypothesized that laboratory methods and CoaguChek XS could produce different
      results according to fibrinogen level. METHODS: We compared INR values obtained
      from the CoaguChek XS and conventional laboratory method with 91 plasma samples
      covering a wide range of fibrinogen levels. RESULTS: The samples were stratified
      into low, mid, and high fibrinogen groups by fibrinogen levels of <130 mg/dl, 130
      450 mg/dl, and >450 mg/dl, respectively. The mean INR difference of the low
      fibrinogen group was significantly different from that of the mid or high
      fibrinogen group (P < 0.001). In the low fibrinogen group, CoaguChek XS INR
      showed a negative bias compared with the laboratory INR, while the mid and high
      fibrinogen groups had positive bias. CONCLUSION: Our results suggest that patient
      selection according to fibrinogen status should precede the implementation of POC
      testing using CoaguChek XS. Also, periodic comparisons between CoaguChek XS and
      laboratory INR results should be continued during the use of CoaguChek XS.

PMID- 24687902
TI  - Hierarchical MoS2 shells supported on carbon spheres for highly reversible
      lithium storage.
AB  - Hierarchical MoS2 shells supported on carbon spheres (denoted as C@MoS2) have
      been synthesized through a one-step hydrothermal method. The obtained
      hierarchical C@MoS2 microspheres simultaneously integrate the structural and
      compositional design rationales for high-energy electrode materials based on two
      dimensional (2D) nanosheets. When evaluated as an anode material for lithium-ion
      batteries (LIBs), the hierarchical C@MoS2 microspheres manifest high specific
      capacity, enhanced cycling stability and good rate capability.

PMID- 24687903
TI  - Interactive biotic and abiotic regulators of soil carbon cycling: evidence from
      controlled climate experiments on peatland and boreal soils.
AB  - Partially decomposed plant and animal remains have been accumulating in organic
      soils (i.e. >40% C content) for millennia, making them the largest terrestrial
      carbon store. There is growing concern that, in a warming world, soil biotic
      processing will accelerate and release greenhouse gases that further exacerbate
      climate change. However, the magnitude of this response remains uncertain as the
      constraints are abiotic, biotic and interactive. Here, we examined the influence
      of resource quality and biological activity on the temperature sensitivity of
      soil respiration under different soil moisture regimes. Organic soils were
      sampled from 13 boreal and peatland ecosystems located in the United Kingdom,
      Ireland, Spain, Finland and Sweden, representing a natural resource quality range
      of C, N and P. They were incubated at four temperatures (4, 10, 15 and 20 
      degrees C) at either 60% or 100% water holding capacity (WHC). Our results showed
      that chemical and biological properties play an important role in determining
      soil respiration responses to temperature and moisture changes. High soil C : P
      and C : N ratios were symptomatic of slow C turnover and long-term C
      accumulation. In boreal soils, low bacterial to fungal ratios were related to
      greater temperature sensitivity of respiration, which was amplified in drier
      conditions. This contrasted with peatland soils which were dominated by bacterial
      communities and enchytraeid grazing, resulting in a more rapid C turnover under
      warmer and wetter conditions. The unexpected acceleration of C mineralization
      under high moisture contents was possibly linked to the primarily role of
      fermented organic matter, instead of oxygen, in mediating microbial
      decomposition. We conclude that to improve C model simulations of soil
      respiration, a better resolution of the interactions occurring between climate,
      resource quality and the decomposer community will be required.

PMID- 24687904
TI  - JC virus reactivation during prolonged natalizumab monotherapy for multiple
      sclerosis.
AB  - OBJECTIVE: To determine the prevalence of JC virus (JCV) reactivation and JCV
      specific cellular immune response during prolonged natalizumab treatment for
      multiple sclerosis (MS). METHODS: We enrolled 43 JCV-seropositive MS patients,
      including 32 on natalizumab monotherapy >18 months, 6 on interferon beta-1a
      monotherapy >36 months, and 5 untreated controls. We performed quantitative real
      time polymerase chain reaction in cerebrospinal fluid (CSF), blood, and urine for
      JCV DNA, and we determined JCV-specific T-cell responses using enzyme-linked
      immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) assays, ex
      vivo and after in vitro stimulation with JCV peptides. RESULTS: JCV DNA was
      detected in the CSF of 2 of 27 (7.4%) natalizumab-treated MS patients who had no
      symptoms or magnetic resonance imaging-detected lesions consistent with
      progressive multifocal leukoencephalopathy. JCV DNA was detected in blood of 12
      of 43 (27.9%) and in urine of 11 of 43 (25.6%) subjects without a difference
      between natalizumab-treated patients and controls. JC viral load was higher in
      CD34(+) cells and in monocytes compared to other subpopulations. ICS was more
      sensitive than ELISpot. JCV-specific T-cell responses, mediated by both CD4(+)
      and CD8(+) T lymphocytes, were detected more frequently after in vitro
      stimulation. JCV-specific CD4(+) T cells were detected ex vivo more frequently in
      MS patients with JCV DNA in CD34(+) (p = 0.05) and B cells (p = 0.03).
      INTERPRETATION: Asymptomatic JCV reactivation may occur in CSF of natalizumab
      treated MS patients. JCV DNA load is higher in circulating CD34(+) cells and
      monocytes compared to other mononuclear cells, and JCV in blood might trigger a
      JCV-specific CD4(+) T-cell response. JCV-specific cellular immune response is
      highly prevalent in all JCV-seropositive MS patients, regardless of treatment.

PMID- 24687905
TI  - Testing the role of circadian genes in conferring risk for psychiatric disorders.
AB  - Disturbed sleep and disrupted circadian rhythms are a common feature of
      psychiatric disorders, and many groups have postulated an association between
      genetic variants in circadian clock genes and psychiatric disorders. Using
      summary data from the association analyses of the Psychiatric Genomics Consortia
      (PGC) for schizophrenia, bipolar disorder and major depressive disorder, we
      evaluated the evidence that common SNPs in genes encoding components of the
      molecular clock influence risk to psychiatric disorders. Initially, gene-based
      and SNP P-values were analyzed for 21 core circadian genes. Subsequently, an
      expanded list of genes linked to control of circadian rhythms was analyzed. After
      correcting for multiple comparisons, none of the circadian genes were
      significantly associated with any of the three disorders. Several genes
      previously implicated in the etiology of psychiatric disorders harbored no SNPs
      significant at the nominal level of P < 0.05, and none of the the variants
      identified in candidate studies of clock genes that were included in the PGC
      datasets were significant after correction for multiple testing. There was no
      evidence of an enrichment of associations in genes linked to control of circadian
      rhythms in human cells. Our results suggest that genes encoding components of the
      molecular clock are not good candidates for harboring common variants that
      increase risk to bipolar disorder, schizophrenia, or major depressive disorder.

PMID- 24687906
TI  - Hollow-structured mesoporous materials: chemical synthesis, functionalization and
      applications.
AB  - Hollow-structured mesoporous materials (HMMs), as a kind of mesoporous material
      with unique morphology, have been of great interest in the past decade because of
      the subtle combination of the hollow architecture with the mesoporous
      nanostructure. Benefitting from the merits of low density, large void space,
      large specific surface area, and, especially, the good biocompatibility, HMMs
      present promising application prospects in various fields, such as adsorption and
      storage, confined catalysis when catalytically active species are incorporated in
      the core and/or shell, controlled drug release, targeted drug delivery, and
      simultaneous diagnosis and therapy of cancers when the surface and/or core of the
      HMMs are functionalized with functional ligands and/or nanoparticles, and so on.
      In this review, recent progress in the design, synthesis, functionalization, and
      applications of hollow mesoporous materials are discussed. Two main synthetic
      strategies, soft-templating and hard-templating routes, are broadly sorted and
      described in detail. Progress in the main application aspects of HMMs, such as
      adsorption and storage, catalysis, and biomedicine, are also discussed in detail
      in this article, in terms of the unique features of the combined large void space
      in the core and the mesoporous network in the shell. Functionalization of the
      core and pore/outer surfaces with functional organic groups and/or nanoparticles,
      and their performance, are summarized in this article. Finally, an outlook of
      their prospects and challenges in terms of their controlled synthesis and scaled
      application is presented. 

PMID- 24687907
TI  - Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of
      neuroendocrine tumors.
AB  - PURPOSE: To demonstrate the safety of outpatient 7.8 GBq (177)Lu-DOTA-tyr(3)
      octreotate radiopeptide therapy of neuroendocrine tumors by measurement of
      radiation exposures of hospital personnel, carers and members of the public.
      METHODS: Seventy-six patients with progressive, metastatic neuroendocrine tumors
      each received four cycles of prescribed activity of 7.8 GBq (177)Lu-octreotate at
      8-week intervals, as an outpatient procedure. Cohorts comprising four patients
      were treated in one room, each patient remaining in hospital until radiation
      exposure from them was below the release limit of 25 MUSv h(-1) at 1 m. On
      occasion, a single patient was treated in a single room. Radiation exposures of
      hospital staff and patient carers were monitored by personal dosimeter, and
      nearby areas monitored with a survey meter. RESULTS: Mean whole-body radiation
      exposures per therapy day ranged from 8 MUSv (physicist) to 33 MUSv (nurse), with
      exposures to personnel, carers and members of the public well within the limits
      recommended by the International Commission on Radiological Protection. Patients
      excreted a mean of 46 % of the total administered activity of (177)Lu-octreotate
      within 4 h of therapy. CONCLUSION: Lutetium-177-octreotate radiopeptide therapy
      of neuroendocrine tumors can be safely performed as an outpatient treatment.

PMID- 24687908
TI  - Fruit and vegetable consumption and non-communicable disease: time to update the
      '5 a day' message?

PMID- 24687909
TI  - Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis
      of Health Survey for England data.
AB  - BACKGROUND: Governments worldwide recommend daily consumption of fruit and
      vegetables. We examine whether this benefits health in the general population of
      England. METHODS: Cox regression was used to estimate HRs and 95% CI for an
      association between fruit and vegetable consumption and all-cause, cancer and
      cardiovascular mortality, adjusting for age, sex, social class, education, BMI,
      alcohol consumption and physical activity, in 65 226 participants aged 35+ years
      in the 2001-2008 Health Surveys for England, annual surveys of nationally
      representative random samples of the non-institutionalised population of England
      linked to mortality data (median follow-up: 7.7 years). RESULTS: Fruit and
      vegetable consumption was associated with decreased all-cause mortality (adjusted
      HR for 7+ portions 0.67 (95% CI 0.58 to 0.78), reference category <1 portion).
      This association was more pronounced when excluding deaths within a year of
      baseline (0.58 (0.46 to 0.71)). Fruit and vegetable consumption was associated
      with reduced cancer (0.75 (0.59-0.96)) and cardiovascular mortality (0.69 (0.53
      to 0.88)). Vegetables may have a stronger association with mortality than fruit
      (HR for 2 to 3 portions 0.81 (0.73 to 0.89) and 0.90 (0.82 to 0.98),
      respectively). Consumption of vegetables (0.85 (0.81 to 0.89) per portion) or
      salad (0.87 (0.82 to 0.92) per portion) were most protective, while frozen/canned
      fruit consumption was apparently associated with increased mortality (1.17 (1.07
      to 1.28) per portion). CONCLUSIONS: A robust inverse association exists between
      fruit and vegetable consumption and mortality, with benefits seen in up to 7+
      portions daily. Further investigations into the effects of different types of
      fruit and vegetables are warranted.

PMID- 24687911
TI  - CO2 captured in zeolitic imidazolate frameworks: Raman spectroscopic analysis of
      uptake and host-guest interactions.
AB  - Zeolitic imidazolate frameworks (ZIFs) exhibit enhanced selectivity and increased
      CO2 uptake due to the incorporation of functional imidazolate units in their
      structure as well as their extensive porosity and ring flexibility. In situ Raman
      investigation of a representative host compound, ZIF-69, in practical CO2
      pressure and temperature regimes (0-10 bar and 0-64  degrees C) correlates well
      with corresponding macroscopic CO2 sorption data and shows clear clear
      spectroscopic evidence of CO2 uptake. Significant positive shift of the 159 cm(
      1) phenyl bending mode of the benzimidazole moiety indicates weak hydrogen
      bonding with CO2 in the larger cavities of the ZIF matrix. Raman spectroscopy is
      shown to be an easy and sensitive tool for quantifying CO2 uptake, identifying
      weak host-guest interactions and elucidating CO2 sorption mechanism in ZIFs. 

PMID- 24687910
TI  - Long-term cardiovascular consequences of Rose angina at age 20-54 years: 29
      years' follow-up of the Tromso Study.
AB  - BACKGROUND: The Rose Angina Questionnaire (RAQ) was constructed in the 1960s for
      assessing the population burden of angina. Studies have found that screening
      positivity by RAQ conferred an elevated risk of coronary heart disease (CHD). It
      is, however, not clear to what extent Rose angina represents early CHD in
      relatively young adults who are free of known CHD. If representing CHD, Rose
      angina is expected to carry prognostic information in addition to the risk
      conferred by other risk factors. METHODS: The Tromso Study is a population-based
      cohort study in Northern Norway. All men aged 20-54 years (n=8238) and women aged
      20-49 years (n=8001), free of known cardiovascular disease (CVD), who
      participated in a survey 1979-1980, were followed throughout 2010 for incident
      myocardial infarction (MI), and for incident MI or stroke used as proxy for
      incident CVD. HRs were estimated using a Cox proportional hazard regression
      model. RESULTS: In age-adjusted analyses, Rose angina predicted MI and CVD in
      both sexes. The excess risk was substantially accounted for by CVD risk factors,
      leaving no significantly elevated MI risk above the risk explained by these
      factors (adjusted HR 1.31; 95% CI 0.95 to 1.80 in men, HR 1.20; 95% CI 0.69 to
      2.10 in women). A similar pattern was seen for CVD (adjusted HR 1.16; 95% CI 0.87
      to 1.55 in men and 1.30; 95% CI 0.82 to 2.06 in women). CONCLUSIONS: Rose angina
      predicted MI and CVD in a 29-years' follow-up of a relatively young population.
      Established CVD risk factors were important mediators.

PMID- 24687912
TI  - White coat, patient gown.
AB  - Much has been written about the symbolic function of the white coat: its
      implications of purity, its representation of authority and professionalism, and
      its role in consolidating a medical hierarchy. By contrast, the medical
      literature has paid almost no attention to the patient gown. In this article, we
      argue that in order to understand the full implications of the white coat in the
      doctor-patient relationship, we must also take into account patients' dress, and
      even undress. We explore contemporary artistic images of white coat and patient
      gown in order to reveal the power differential in the doctor-patient
      relationship. Artistic representations capture some of the cultural ambivalence
      surrounding the use of the white coat, which confers professional status on its
      wearer, while undermining his or her personal identity. At the other end of the
      sartorial spectrum, hospital gowns also strip wearers of their identity, but add
      to this an experience of vulnerability. Although compelling reasons for
      continuing to wear the white coat in circumscribed settings persist, physicians
      should be mindful of its hierarchical implications. Ample room remains for
      improving patients' privacy and dignity by updating the hospital gown. 

PMID- 24687913
TI  - An activation of LC3A-mediated autophagy contributes to de novo and acquired
      resistance to EGFR tyrosine kinase inhibitors in lung adenocarcinoma.
AB  - The development of therapeutic resistance to EGFR tyrosine kinase inhibitors
      (EGFR-TKIs, ie erlotinib or gefitinib) has been the major clinical problem when
      treating lung adenocarcinoma patients with these agents. However, its mechanisms
      have not necessarily been well studied to this date. Autophagy has been recently
      considered to play pivotal roles in escaping from the effects of anti-neoplastic
      agents. Therefore, in this study, we examined its roles in the development of
      resistance to EGFR-TKIs in lung adenocarcinoma. We first established erlotinib
      resistant cell lines (PC9/ER) from parental PC9 cells by exposing the cells to
      erlotinib. In PC9/ER, autophagy-related LC3A expression came to be up-regulated
      and constitutive activation of LC3A-mediated autophagy became more pronounced
      through the process of acquiring therapeutic resistance. In addition, inhibition
      of LC3A or autophagy restores sensitivity to EGFR-TKIs in PC9/ER. LC3A was also
      activated at the transcriptional level in de novo resistant cells via
      demethylation of the MAP1LC3A gene. We then evaluated the status of LC3A in 169
      lung adenocarcinoma patients using immunohistochemistry. LC3A immunoreactivity
      was only detected in carcinoma cells (89/169 patients), not in non-tumoural
      cells. In addition, LC3A immunoreactivity was significantly correlated with
      progression-free survival (p = 0.0039) and overall survival (p = 0.0040) of 35
      patients treated with EGFR-TKIs. The results of our present study demonstrated
      that LC3A-mediated autophagy in carcinoma cells was involved in the development
      of resistance to EGFR-TKIs, and that LC3A could serve as a promising therapeutic
      target for overcoming resistance to EGFR-TKIs and a novel predictor of response
      to EGFR-TKIs in lung adenocarcinoma patients.

PMID- 24687914
TI  - Regioselective functionalization of core-persubstituted perylene diimides.
AB  - Regioselective functionalization of core per-substituted perylene diimides has
      been achieved efficiently based on a new versatile building block, named
      tetrabromotetrachloro-perylene-3,4:9,10-tetracarboxylic acid dianhydride (Br4Cl4
      PTCDA), which affords a series of novel chromophores with impressive
      optoelectronic properties. Direct palladium-catalyzed fourfold intramolecular
      ring fusion affords successfully unique propeller-shaped biscarbazole[2,3
      b]carbazole diimides with six annulated rings.

PMID- 24687915
TI  - Modulation of amyloid precursor protein expression reduces beta-amyloid
      deposition in a mouse model.
AB  - OBJECTIVE: Proteolytic cleavage of the amyloid precursor protein (APP) generates
      beta-amyloid (Abeta) peptides. Prolonged accumulation of Abeta in the brain
      underlies the pathogenesis of Alzheimer disease (AD) and is regarded as a
      principal target for development of disease-modifying therapeutics. METHODS:
      Using Chinese hamster ovary (CHO) APP751SW cells, we identified and characterized
      effects of 2-([pyridine-2-ylmethyl]-amino)-phenol (2-PMAP) on APP steady-state
      level and Abeta production. Outcomes of 2-PMAP treatment on Abeta accumulation
      and associated memory deficit were studied in APPSW /PS1dE9 AD transgenic model
      mice. RESULTS: In CHO APP751SW cells, 2-PMAP lowered the steady-state APP level
      and inhibited Abetax-40 and Abetax-42 production in a dose-response manner with a
      minimum effective concentration <= 0.5MUM. The inhibitory effect of 2-PMAP on
      translational efficiency of APP mRNA into protein was directly confirmed using a
      35S-methionine/cysteine metabolic labeling technique, whereas APP mRNA level
      remained unaltered. Administration of 2-PMAP to APPSW /PS1dE9 mice reduced brain
      levels of full-length APP and its C-terminal fragments and lowered levels of
      soluble Abetax-40 and Abetax-42 . Four-month chronic treatment of APPSW /PS1dE9
      mice revealed no observable toxicity and improved animals' memory performance. 2
      PMAP treatment also caused significant reduction in brain Abeta deposition
      determined by both unbiased quantification of Abeta plaque load and biochemical
      analysis of formic acid-extracted Abetax-40 and Abetax-42 levels and the level of
      oligomeric Abeta. INTERPRETATION: We demonstrate the potential of modulating APP
      steady-state expression level as a safe and effective approach for reducing Abeta
      deposition in AD transgenic model mice.

PMID- 24687916
TI  - Climate change may have limited effect on global risk of potato late blight.
AB  - Weather affects the severity of many plant diseases, and climate change is likely
      to alter the patterns of crop disease severity. Evaluating possible future
      patterns can help focus crop breeding and disease management research. We
      examined the global effect of climate change on potato late blight, the disease
      that caused the Irish potato famine and still is a common potato disease around
      the world. We used a metamodel and considered three global climate models for the
      A2 greenhouse gas emission scenario for three 20-year time-slices: 2000-2019,
      2040-2059 and 2080-2099. In addition to global analyses, five regions were
      evaluated where potato is an important crop: the Andean Highlands, Indo-Gangetic
      Plain and Himalayan Highlands, Southeast Asian Highlands, Ethiopian Highlands,
      and Lake Kivu Highlands in Sub-Saharan Africa. We found that the average global
      risk of potato late blight increases initially, when compared with historic
      climate data, and then declines as planting dates shift to cooler seasons. Risk
      in the agro-ecosystems analyzed, varied from a large increase in risk in the Lake
      Kivu Highlands in Rwanda to decreases in the Southeast Asian Highlands of
      Indonesia. 

PMID- 24687918
TI  - Co-occurrence of monoclonal gammopathy and myelodysplasia: a retrospective study
      of fourteen cases.
AB  - We report a series of 14 patients with myelodysplastic syndrome (MDS) accompanied
      by a monoclonal gammopathy unrelated to therapy. Twelve of these had monoclonal
      gammopathy of undermined significance (MGUS) and two had smoldering multiple
      myeloma. These cases represent 10.2 % of all MDS cases seen at our institution
      over a 14-year period (January 2000 to December 2013). The incidence of MGUS was
      determined to be significantly higher in MDS than in age-matched concurrent
      controls by chi(2) test. Absence of prior chemotherapy and simultaneous
      presentation of MDS and MGUS in most cases suggest true co-occurrence of the two
      disorders. MGUS was found in all WHO subtypes of MDS with a wide range of risk
      factors. However, 11 out of the 12 MDS cases accompanied with MGUS had relatively
      low karyotypic risks. In addition, serum M protein levels remained largely
      unchanged in 4 cases of MGUS for which serial determinations were performed.
      These findings indicate that MGUS may not affect the prognosis of MDS.

PMID- 24687917
TI  - Small RNA as a regulator of hematopoietic development, immune response in
      infection and tumorigenesis.
AB  - Posttranscriptional gene regulation by small RNAs (15-40-nucleotide noncoding
      RNAs) is now established as an important branch of the gene regulatory system. It
      has recently been revealed that noncoding RNAs can be categorized into different
      types and that they work through novel mechanisms. In addition, it has been shown
      that noncoding RNAs mediate intercellular communication and, importantly, that
      cross talk between coding and noncoding RNAs occurs. In this review, we discuss
      the recent findings concerning small RNAs. It was originally proposed that
      microRNAs (miRNAs) work to "fine tune" the determination of cell fate. However,
      critical functions beyond fine tuning have been revealed. In addition to miRNAs,
      next-generation sequencing has revealed the existence of various species of non
      canonical small RNAs: mirtrons, piRNAs, 21U-RNA, endo-siRNAs, snoRNAs, usRNAs,
      and Y-RNA-derived small RNAs. Some of these species are involved in response to
      viral infection. Finally, we highlight the intracellular functions of small RNAs,
      which involve the exosomes. 

PMID- 24687919
TI  - Tissue factor pathway inhibitor in activated prothrombin complex concentrates
      (aPCC) moderates the effectiveness of therapy in some severe hemophilia A
      patients with inhibitor.
AB  - Some hemophilia A patients who have developed inhibitors are poorly responsive to
      activated prothrombin complex concentrates (aPCC) after daily dosage, but the
      mechanism(s) underlying this remain unknown. We examined two representative
      cases. In case 1, we found that changing to recombinant factor VIIa (rFVIIa)
      therapy was more effective, and the response to aPCC was restored within ~2
      weeks. Tissue factor (TF)-triggered thrombin generation demonstrated a prolonged
      lag-time and decreased peak thrombin, and this impairment was focused on TF
      pathway inhibitor (TFPI). Plasma-free TFPI was elevated post-infusion of aPCC,
      while this was unaffected by rFVIIa. TFPI returned to normal range within 2-3
      weeks. Plasmas obtained from patients with poor or good response to aPCC (aPCC
      poor or aPCC-good), and good response to rFVIIa (FVIIa-good) demonstrated that
      free TFPI levels are increased in both aPCC groups, but not in FVIIa-good. TFPI
      levels pre- and post-infusion in aPCC-poor were significantly higher than those
      in aPCC-good. Addition of anti-TFPI antibody to the reaction samples demonstrated
      a greater increase of peak thrombin in aPCC-poor compared to aPCC-good, showing
      the higher TFPI activity in aPCC-poor. Free TFPI contained in aPCC corresponded
      to the increasing levels in plasma. In conclusion, TFPI in aPCC attenuated
      thrombin generation, and the reduced effectiveness of therapy in these
      circumstances appeared to be related to TFPI activity.

PMID- 24687920
TI  - High frequency of antiphospholipid antibodies in primary biliary cirrhosis.
AB  - AIM: To evaluate, retrospectively, the frequency of autoantibodies of
      antiphospholipid syndrome (APLS) in Tunisian patients with primary biliary
      cirrhosis (PBC). PATIENTS AND METHODS: We analyzed 80 PBC sera and 80 sera from
      blood donors. ELISA was used to determine the frequency of antibodies against
      cardiolipin (aCL IgG, IgA, and IgM) and beta 2 glycoprotein I (abeta2GPI IgG,
      IgA, and IgM). RESULTS: The frequency of antiphospholipid antibodies (aCL and/or
      abeta2GPI) was significantly higher in PBC patients than in controls (70 vs. 5%,
      P < 10(-6)). The frequency of aCL antibodies (IgG, IgA or IgM) was significantly
      higher in PBC patients than in the control group (23.7 vs. 3.7%, P = 0.0005). The
      frequencies of aCL IgA and aCL IgM in PBC patients' sera were significantly
      higher than those in the control group (10 vs. 0%, P = 0.003 and 20 vs. 2.5%, P =
      0.001, respectively). Two patients of eighty (2.5%) had aCL IgG, aCL IgA and aCL
      IgM. The frequency of abeta2GPI antibodies (IgG, IgA, or IgM) was significantly
      higher in PBC patients than in the control group (70 vs. 1.2%, P < 10(-6)). The
      frequencies of abeta2GPI IgG, abeta2GPI IgA, and abeta2GPI IgM in PBC patients'
      sera were significantly higher in patients than in the control group (12.5 vs.
      0%, P = 0.003; 62.5 vs. 1.2%, P < 10(-6); and 21.2 vs. 0%, P < 10(-4),
      respectively). CONCLUSION: Autoantibodies related to APLS (aCL and abeta2GPI)
      were present in the majority of patients with PBC, reflecting the ability of
      these antibodies to engage mediators of damage.

PMID- 24687921
TI  - Biomarker analyses from a placebo-controlled phase II study evaluating
      erlotinib+/-onartuzumab in advanced non-small cell lung cancer: MET expression
      levels are predictive of patient benefit.
AB  - PURPOSE: In a recent phase II study of onartuzumab (MetMAb), patients whose non
      small cell lung cancer (NSCLC) tissue scored as positive for MET protein by
      immunohistochemistry (IHC) experienced a significant benefit with onartuzumab
      plus erlotinib (O+E) versus erlotinib. We describe development and validation of
      a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers
      as predictors of patient benefit. EXPERIMENTAL DESIGN: Biomarkers related to MET
      and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative
      reverse transcription PCR, mutation detection techniques, and ELISA. RESULTS: A
      positive correlation between IHC, Western blotting, and MET mRNA expression was
      observed in NSCLC cell lines/tissues. An IHC scoring system of MET expression
      taking proportional and intensity-based thresholds into consideration was applied
      in an analysis of the phase II study and resulted in the best differentiation of
      outcomes. Further analyses revealed a nonsignificant overall survival (OS)
      improvement with O+E in patients with high MET copy number (mean>=5 copies/cell
      by FISH); however, benefit was maintained in "MET IHC-positive"/MET FISH-negative
      patients (HR, 0.37; P=0.01). MET, EGFR, amphiregulin, epiregulin, or HGF mRNA
      expression did not predict a significant benefit with onartuzumab; a
      nonsignificant OS improvement was observed in patients with high tumor MET mRNA
      levels (HR, 0.59; P=0.23). Patients with low baseline plasma hepatocyte growth
      factor (HGF) exhibited an HR for OS of 0.519 (P=0.09) in favor of onartuzumab
      treatment. CONCLUSIONS: MET IHC remains the most robust predictor of OS and
      progression-free survival benefit from O+E relative to all examined exploratory
      markers.

PMID- 24687922
TI  - Treatment response evaluation using 18F-FDOPA PET in patients with recurrent
      malignant glioma on bevacizumab therapy.
AB  - PURPOSE: This study compares the value of 3,4-dihydroxy-6-[(18)F]-fluoro-l
      phenylalanine ((18)F-FDOPA) positron emission tomography (PET) and MRI in
      assessing outcome during antiangiogenic treatment in patients with recurrent high
      grade gliomas. EXPERIMENTAL DESIGN: Thirty patients were prospectively studied
      with (18)F-FDOPA PET scans immediately before, and two and six weeks after start
      of bevacizumab therapy. (18)F-FDOPA metabolic tumor volumes (MTV) as well as max
      and mean standardized uptake values (SUV) within this MTV were obtained. MRI
      treatment response was assessed at six weeks. The predictive ability of (18)F
      FDOPA PET and MRI response assessment were evaluated with regard to progression
      free survival (PFS) and overall survival (OS). RESULTS: A total of 30, 28, and 24
      (18)F-FDOPA PET scans at baseline, two weeks, and six weeks, were available for
      analysis, respectively. (18)F-FDOPA PET SUVs as well as their changes through
      therapy were not predictive of outcome. However, MTV parameters such as MTV
      changes were highly prognostic. Interestingly, absolute MTV at the first follow
      up scan provides the most significant prediction for increased OS (P < 0.0001) as
      well as PFS (P = 0.001). This surprising result was scrutinized with cross
      validation and simulation analysis. Responders based on (18)F-FDOPA PET data
      survived 3.5 times longer (12.1 months vs. 3.5 months, median OS, P < 0.001) than
      nonresponders (17 patients vs. 11 patients, respectively). In comparison,
      responders based on MRI data lived 1.5 times longer (11.4 months vs 7.7 months, P
      = 0.03) than nonresponders (22 patients vs. 7 patients, respectively).
      CONCLUSIONS: (18)F-FDOPA PET identifies treatment responders to antiangiogenic
      therapy as early as two weeks after treatment initiation.

PMID- 24687923
TI  - Zoledronic acid has differential antitumor activity in the pre- and
      postmenopausal bone microenvironment in vivo.
AB  - PURPOSE: Clinical trials in early breast cancer have suggested that benefits of
      adjuvant bone-targeted treatments are restricted to women with established
      menopause. We developed models that mimic pre- and postmenopausal status to
      investigate effects of altered bone turnover on growth of disseminated breast
      tumor cells. Here, we report a differential antitumor effect of zoledronic acid
      (ZOL) in these two settings. EXPERIMENTAL DESIGN: Twleve-week-old female Balb/c
      nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham
      operation or ovariectomy (OVX), mimicking the pre- and postmenopausal bone
      microenvironment, respectively. To determine the effects of bone-targeted
      therapy, sham/OVX animals received saline or 100 MUg/kg ZOL weekly. Tumor growth
      was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT,
      histomorphometry, and measurements of bone markers. Disseminated tumor cells were
      detected by two-photon microscopy. RESULTS: OVX increased bone resorption and
      induced growth of disseminated tumor cells in bone. Tumors were detected in 83%
      of animals following OVX (postmenopausal model) compared with 17% following sham
      operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX
      induced tumor growth was completely prevented by ZOL, despite the presence of
      disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham
      operated animals. ZOL increased bone volume in both groups. CONCLUSIONS: This is
      the first demonstration that tumor growth is driven by osteoclast-mediated
      mechanisms in models that mimic post- but not premenopausal bone, providing a
      biologic rationale for the differential antitumor effects of ZOL reported in
      these settings. Clin Cancer Res; 20(11); 2922-32. (c)2014 AACR.

PMID- 24687925
TI  - Proteomic markers of DNA repair and PI3K pathway activation predict response to
      the PARP inhibitor BMN 673 in small cell lung cancer--letter.

PMID- 24687924
TI  - Proteomic markers of DNA repair and PI3K pathway activation predict response to
      the PARP inhibitor BMN 673 in small cell lung cancer--response.

PMID- 24687926
TI  - SPINK1 protein expression and prostate cancer progression.
AB  - PURPOSE: SPINK1 overexpression has been described in prostate cancer and is
      linked with poor prognosis in many cancers. The objective of this study was to
      characterize the association between SPINK1 overexpression and prostate cancer
      specific survival. EXPERIMENTAL DESIGN: The study included 879 participants in
      the U.S. Physicians' Health Study and Health Professionals Follow-Up Study,
      diagnosed with prostate cancer (1983-2004) and treated by radical prostatectomy.
      Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor
      tissue microarrays. RESULTS: Seventy-four of 879 (8%) prostate cancer tumors were
      SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6,
      stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG
      translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors
      showed higher PTEN and stathmin expression, and lower expression of AR (P <
      0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and
      in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant
      associations between SPINK1 status and Gleason grade or tumor stage. There was no
      association between SPINK1 expression and biochemical recurrence (P = 0.56).
      Moreover, there was no association between SPINK1 expression and prostate cancer
      mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5
      years follow-up; HR = 0.71; 95% confidence interval, 0.29-1.76). CONCLUSIONS: Our
      results suggest that SPINK1 protein expression may not be a predictor of
      recurrence or lethal prostate cancer amongst men treated by radical
      prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely
      mutually exclusive, as some previous studies have suggested.

PMID- 24687930
TI  - Organic thermoelectric materials: emerging green energy materials converting heat
      to electricity directly and efficiently.
AB  - The abundance of solar thermal energy and the widespread demands for waste heat
      recovery make thermoelectric generators (TEGs) very attractive in harvesting low
      cost energy resources. Meanwhile, thermoelectric refrigeration is promising for
      local cooling and niche applications. In this context there is currently a
      growing interest in developing organic thermoelectric materials which are
      flexible, cost-effective, eco-friendly and potentially energy-efficient. In
      particular, the past several years have witnessed remarkable progress in organic
      thermoelectric materials and devices. In this review, thermoelectric properties
      of conducting polymers and small molecules are summarized, with recent progresses
      in materials, measurements and devices highlighted. Prospects and suggestions for
      future research efforts are also presented. The organic thermoelectric materials
      are emerging candidates for green energy conversion. 

PMID- 24687931
TI  - Targeting misuse of 2-amino-N-ethyl-1-phenylbutane in urine samples: in vitro-in
      vivo correlation of metabolic profiles and development of LC-TOF-MS method.
AB  - A phenyethylamine derivative, 2-amino-N-ethyl-1-phenylbutane (2-AEPB), has
      recently been detected in doping control and drugs-of-abuse samples, and
      identified as a non-labelled ingredient in a dietary supplement. To facilitate
      efficient control of this substance we have studied the in vitro metabolic
      behaviour of 2-AEPB with human liver preparation, compared these results with in
      vivo pathways in human, and finally propose an analytical strategy to target the
      potential misuse of 2-AEPB for toxicological, forensic and doping control
      purposes. The major in vitro formed metabolites originated from desethylation
      (M1) and monohydroxylation (M2). A minor metabolite with hydroxylation/N
      oxidation was also observed (M3). In vitro-in vivo correlation was studied in an
      excretion study with a single, oral dose of 2-AEPB-containing supplement. An
      unmodified substance was the most abundant target compound and detected until the
      last point of sample collection (72 h), and the detection of M1 (40 h) and M2 (27
      h) demonstrated good correlation to in vitro results. In the study with authentic
      cases (n = 6), 2-AEPB and M1 were mainly found in free urinary fraction, whereas
      higher inter-individual variability was observed for M2. It was predominantly
      conjugated and already within this limited number of cases, the ratio between
      glucuronide- and sulpho-conjugated fractions varied significantly. As a
      conclusion, hydrolysis is not mandatory in the routine sample preparation, and as
      the separation can be based on either gas chromatography or liquid
      chromatography, this study verifies that routine mass spectrometric detection
      methods targeted to amphetamine derivatives can be easily extended to control the
      misuse of 2-AEPB.

PMID- 24687927
TI  - KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild
      type stage III colon cancers from an adjuvant chemotherapy trial (N0147
      alliance).
AB  - PURPOSE: We examined the prognostic impact of specific KRAS mutations in patients
      with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined
      with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF-wild
      type tumors, because BRAF mutation was associated with poor prognosis, and BRAF
      and KRAS mutations are mutually exclusive. EXPERIMENTAL DESIGN: The seven most
      common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF-wild
      type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were
      not predictive of adjuvant cetuximab benefit, study arms were pooled for
      analysis. Disease-free survival (DFS) was evaluated by HRs using Cox models.
      RESULTS: KRAS mutations in codon 12 (multivariate HR, 1.52; 95% confidence
      interval, CI, 1.28-1.80; P < 0.0001) or codon 13 (multivariate HR, 1.36; 95% CI,
      1.04-1.77; P = 0.0248) were significantly associated with shorter DFS compared
      with patients with wild-type KRAS/BRAF tumors, independent of covariates. KRAS
      codon 12 mutations were independently associated with proficient mismatch repair
      (P < 0.0001), proximal tumor site (P < 0.0001), low grade, age, and sex, whereas
      codon 13 mutations were associated with proximal site (P < 0.0001). CONCLUSION:
      KRAS mutations in either codon 12 or 13 are associated with inferior survival in
      patients with resected stage III colon cancer. These data highlight the
      importance of accurate molecular characterization and the significant role of
      KRAS mutations in both codons in the progression of this malignancy in the
      adjuvant setting. Clin Cancer Res; 20(11); 3033-43. (c)2014 AACR.

PMID- 24687932
TI  - Sustained autoimmune mechanisms in dermatomyositis.
AB  - Dermatomyositis is an autoimmune disease predominantly affecting skin and muscle.
      Its poorly understood pathogenesis is increasingly being linked to the
      overproduction of type 1 interferon-inducible gene transcripts and proteins.
      Mechanisms have been identified by which chronic sustained accumulation of these
      proteins might occur and thereby injure tissue in dermatomyositis.

PMID- 24687938
TI  - Efficient palladium-catalyzed aminocarbonylation of aryl iodides using palladium
      nanoparticles dispersed on siliceous mesocellular foam.
AB  - A highly dispersed nanopalladium catalyst supported on mesocellular foam (MCF),
      was successfully used in the heterogeneous catalysis of aminocarbonylation
      reactions. During the preliminary evaluation of this catalyst it was discovered
      that the supported palladium nanoparticles exhibited a "release and catch"
      effect, meaning that a minor amount of the heterogeneous palladium became soluble
      and catalyzed the reaction, after which it re-deposited onto the support. 

PMID- 24687939
TI  - Endoscopic Repair of Nasal Septal Perforation with "Slide and Patch" Technique.
AB  - OBJECTIVE: The aim of this study is to report our new endoscopic technique for
      the repair of nasal septal perforations, called the "slide and patch" technique
      because it combines a mucoperiosteal free graft of the inferior turbinate with a
      mucosal rotational or advancement flap from the nasal septum. METHODS: Twenty-two
      patients with symptomatic septal nasal perforation of various sizes underwent our
      method of repair. RESULTS: At the last follow-up, 21 (95.4%) perforations were
      closed. There was a partial closure in only 1 patient with a large perforation
      (3.5 cm in diameter). After surgery, 19 (86.3%) patients were asymptomatic, 2
      (9%) showed persistence of crusting, and 1 (4.5%) showed the appearance of nasal
      obstruction 1 month postoperatively. CONCLUSION: The method described herein has
      shown to be effective in nasal septal perforation repair and in nasal symptoms
      relief with the advantage of not requiring grafts from outside the nose.

PMID- 24687940
TI  - Effects of Endoscopic Sinus Surgery and Nasal Surgery in Patients with
      Obstructive Sleep Apnea.
AB  - OBJECTIVES: To evaluate the impact of combined nasal surgery and endoscopic sinus
      surgery on the objective measurements of obstructive sleep apnea (OSA) and sleep
      architecture by comparing polysomnographic data before and after combined surgery
      in patients with OSA. STUDY DESIGN: Case series with chart review. SETTING: A
      single clinical site. SUBJECTS AND METHODS: Patients with OSA and chronic
      rhinosinusitis who underwent combined nasal surgery and endoscopic sinus surgery
      and preoperative and postoperative polysomnography were identified. Patient
      charts were reviewed and preoperative and postoperative body mass index, apnea
      hypopnea index (AHI), mean and minimum oxygen saturation, sleep efficiency, and
      sleep staging were compared. RESULTS: Fifty-six patients were included in our
      study. Patients were divided into 3 groups on the basis of the severity of OSA:
      those with mild OSA (n = 9), those with moderate OSA (n = 23), and those with
      severe OSA (n = 24). After combined nasal and sinus surgery, the mean AHI
      significantly decreased from 33.5 +/- 22.0 to 29.4 +/- 20.8 (P = .009) in our
      overall population. Specifically, AHI improved significantly in patients with
      moderate OSA (from 22.3 +/- 4.8 to 20.7 +/- 8.2, P = .023) and severe OSA (from
      52.3 +/- 21.4 to 43.6 +/- 23.9, P = .034), while patients with mild OSA did not
      have significant changes in AHI. Successful surgical procedures were achieved in
      only 2 of 56 patients. CONCLUSION: Although combined nasal and sinus surgery may
      slightly improve AHI in a certain group of patients, it does not cure OSA or have
      a significant clinical impact.

PMID- 24687941
TI  - Nanoimmunoassay to Detect Responses in Head and Neck Cancer: Feasibility in a
      Mouse Model.
AB  - OBJECTIVE: To demonstrate the feasibility of detecting and quantifying
      extracellular signal-related kinase (ERK) phosphorylation status using
      nanoimmunoassay (NIA). STUDY DESIGN: Analyses using Cal27, SCC25, and OSC19 head
      and neck squamous carcinoma cell lines in vitro and in a murine xenograft model.
      SUBJECTS AND METHODS: NIA and immunoblot were performed on whole-cell lysates,
      tumor lysates, and fine-needle aspirate biopsies to detect ERK phosphorylation
      states. RESULTS: Using NIA, all 6 isoforms of ERK1/2, including
      nonphosphorylated, monophosphorylated, and diphosphorylated species, could be
      reliably detected, distinguished, and quantified in a single assay using a single
      antibody. In vitro treatment of Cal27 cells with the epidermal growth factor
      receptor inhibitor gefitinib abolished phospho-ERK detection by immunoblot but
      resulted in residual detectable species by NIA. Residual phospho-ERK in gefitinib
      treated cells could be further reduced by the addition of the insulin-like growth
      factor 1 receptor inhibitor OSI-906; this correlated with an additional decrease
      in proliferation over gefitinib alone. In a pilot study of 4 murine xenograft
      tumors, NIA performed on tumor lysates and fine-needle aspirate biopsies
      demonstrated altered ERK profiles after 2 days of gefitinib treatment compared
      with untreated mice. CONCLUSION: NIA offers a novel approach to quantitating the
      activation state of signaling molecules such as ERK in nanoscale in vitro and in
      vivo samples across a wide dynamic range. As such, it has potential to provide
      molecular diagnostic information before, during, and after treatment using a
      minimally invasive technique. Further study is warranted to determine its utility
      in assessing signaling proteins as biomolecular outcome predictors in clinical
      trials.

PMID- 24687942
TI  - Rapid Systematic Review of the Epley Maneuver for Treating Posterior Canal Benign
      Paroxysmal Positional Vertigo.
AB  - OBJECTIVE: The aim of this study was to compare watchful waiting to the Epley
      maneuver as a management option for patients with posterior canal benign
      paroxysmal positional vertigo (p-BPPV) regarding symptom relief. DATA SOURCES:
      PubMed, Embase, and The Cochrane Library. METHODS: A systematic search was
      conducted. Studies reporting original study data were included. Relevance and
      risk of bias (RoB) of the selected articles were assessed. Studies with low
      relevance, high RoB, or both were excluded. Absolute risk differences and their
      95% confidence intervals (CIs) were extracted for the included studies. RESULTS:
      A total of 1448 unique studies were retrieved. Eight of these satisfied the
      eligibility criteria. At 1-week follow-up, all included studies reported a
      clinically relevant effect in favor of the Epley maneuver regarding symptom
      relief (absolute risk differences ranging from 20% [95% CI, 5%-37%] to 59% [95%
      CI, 32%-76%]) or conversion to a negative Dix-Hallpike (absolute risk differences
      ranging from 17% [95% CI, -5%-37%] to 64% [95% CI, 29%-79%]). At 1-month follow
      up, the results of the included studies diverged further. Absolute risk
      differences ranged from 6% (95% CI, -24%-35%) more symptom relief in favor of
      watchful waiting to 79% (95% CI, 56%-88%) in favor of the Epley maneuver.
      CONCLUSION AND RECOMMENDATIONS: All data of the selected studies show a benefit
      in favor of the Epley maneuver at 1-week follow-up in the management of p-BPPV.
      The Epley maneuver should be considered in all patients with p-BPPV.

PMID- 24687943
TI  - Otitis Media and Caregiver Quality of Life: Psychometric Properties of the
      Modified Danish Version of the Caregiver Impact Questionnaire.
AB  - OBJECTIVE: Otitis media in children may have a considerable impact on caregiver
      quality of life. The disease-specific Caregiver Impact Questionnaire is designed
      to assess caregiver quality of life in relation to child otitis media. Assessment
      of the psychometric properties of this instrument is limited. This study assesses
      the psychometric properties of this instrument including validity,
      reproducibility, responsiveness, and interpretability. STUDY DESIGN: Longitudinal
      validation study. SETTING: Secondary care units. METHODS: Analyses were based on
      data from 435 families. Validity was assessed using confirmatory factor analysis,
      internal consistency, and hypothesis testing. Test-retest reliability and
      measures of smallest detectable change were investigated in the assessment of
      reproducibility. Responsiveness was investigated by means of hypothesis testing
      and receiver operating characteristic analysis. An anchor-based distribution
      method was applied for determining minimal important change as perceived by the
      respondent. RESULTS: Factor analysis confirmed the hypothesized 1-factor
      structure with an acceptable fit. Cronbach's alpha was .90. In the analysis of
      construct validity, 88.9% of the hypothesized correlations were correctly
      predicted. Intraclass correlation coefficient was 0.87 and smallest detectable
      change corresponded to approximately one-fourth of the scale. Responsiveness was
      found to be good and a change score of 13.8 represented minimal important change.
      CONCLUSION: The modified Danish version of the Caregiver Impact Questionnaire is
      a valid and reproducible measurement tool that is also sensitive to measuring
      change in the current setting. A change score representing minimal important
      change as perceived by the respondent is proposed. Results of this study support
      the use of this instrument.

PMID- 24687944
TI  - Changes in forest biomass and linkage to climate and forest disturbances over
      Northeastern China.
AB  - The forests of northeastern China store nearly half of the country's total
      biomass carbon stocks. In this study, we investigated the changes in forest
      biomass by using satellite observations and found that a significant increase in
      forest biomass took place between 2001 and 2010. To determine the possible
      reasons for this change, several statistical methods were used to analyze the
      correlations between forest biomass dynamics and forest disturbances (i.e. fires,
      insect damage, logging, and afforestation and reforestation), climatic factors,
      and forest development. Results showed that forest development was the most
      important contributor to the increasing trend of forest biomass from 2001 to
      2010, and climate controls were the secondary important factor. Among the four
      types of forest disturbance considered in this study, forest recovery from fires,
      and afforestation and reforestation during the past few decades played an
      important role in short-term biomass dynamics. This study provided observational
      evidence and valuable information for the relationships between forest biomass
      and climate as well as forest disturbances. 

PMID- 24687945
TI  - The differential diagnostic value of serum NT-proBNP in hospitalized patients of
      heart failure with pneumonia.
AB  - Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) is considered as an
      effective predictor for patients with heart failure (HF), while a strong body of
      evidence has found its utility in inflammatory diseases. It is difficult to
      differentiate HF and HF coexisting with other inflammations by measuring NT
      proBNP. The aim of this study was to estimate the differential diagnostic
      performance of serum NT-proBNP in hospitalized HF patients with pneumonia. A
      prospective study was launched. Sixty nine HF patients, 51 HF patients
      complicated with pneumonia, and 38 patients with pneumonia were enrolled. Serum
      NT-proBNP levels were measured on Roche Elecsys. X-ray and the European Society
      of Cardiology (ESC) diagnostic principles were adopted to identify patients with
      pneumonia and HF, respectively. The diagnostic performance of NT-proBNP was
      assessed by ROC. Serum NT-proBNP [7,039(1,008-24,672) pg/ml] in patients of HF
      complicated with pneumonia was significantly higher than that in those of
      patients with single HF [3,147(616-24,062) pg/ml] or single pneumonia [911(98
      3,812) pg/ml] (P < 0.0001). No correlation was found between the level of NT
      proBNP and hospital stay. The area under ROC curve (AUC) of NT-proBNP for
      distinguishing patients of HF with pneumonia was 0.8082. At the level of 4,691
      pg/ml, the optimal cutoff value, 74.5% sensitivity and 81.8% specificity of NT
      proBNP were predicted. Evaluation of serum NT-proBNP is conducive for clinicians
      to identify patients of HF with pneumonia, but its poor efficacy in monitoring
      the curative therapy in this entire cohort is not recommended. 

PMID- 24687946
TI  - Controllable printing droplets for high-resolution patterns.
AB  - Inkjet printing has attracted wide attention due to the important applications in
      fabricating biological, optical, and electrical devices. During the inkjet
      printing process, the solutes prefer to deposit along the droplet periphery and
      form an inhomogeneous morphology, known as the coffee-ring effect. Besides, the
      feature size of printed dots or lines of conventional inkjet printing is usually
      limited to tens or even hundreds of micrometers. The above two issues greatly
      restrict the extensive application of printed patterns in high-performance
      devices. This paper reviews the recent advances in precisely controlling the
      printing droplets for high-resolution patterns and three-dimensional structures,
      with a focus on the development to suppress the coffee-ring effect and minimize
      the feature size of printed dots or lines. A perspective on the remaining
      challenges of the research is also proposed. 

PMID- 24687947
TI  - Rapid and sensitive liquid chromatography with tandem mass spectrometry method
      for the simultaneous determination of 11 major components of Yuanhu-Baizhi herb
      pair in rat perfusion fluids.
AB  - A rapid and sensitive liquid chromatography with tandem mass spectrometry method
      has been developed and validated for the simultaneous quantification of 11 major
      compounds in Yuanhu-Bazhi herb-pair from a rat intestinal perfusion experiment,
      including eight alkaloids and three coumarins using diazepam as the internal
      standard. The analysis was performed on an Agilent Poroshell 120EC-C18 column
      using a gradient elution of acetonitrile/H2 O with 0.0015% formic acid and 2 mM
      ammonium formate buffer additive (pH 4.2). All compounds were detected by tandem
      mass spectrometry in positive ionization mode and quantified using multiple
      reaction monitoring mode. Good linearity in the related range of each compound
      was presented. The validation data, such as accuracy and precision, were within
      the required limits. The lower limit of quantification of each analyte was less
      than 10 ng/mL. Intra-day and inter-day precisions were less than 12.84%. The
      relative errors of accuracy were in the range of -13.31 to 13.19%. The recoveries
      of analytes were greater than 84.08%. The method has been successfully applied to
      an intestinal absorption study of major components following intestinal perfusion
      of Yuanhu-Bazhi herb-pair extract to rats. 

PMID- 24687948
TI  - Structural determinants of the interaction between the Haemophilus influenzae Hap
      autotransporter and fibronectin.
AB  - Haemophilus influenzae is a Gram-negative cocco-bacillus that initiates infection
      by colonizing the upper respiratory tract. Hap is an H. influenzae serine
      protease autotransporter protein that mediates adherence, invasion and
      microcolony formation in assays with human epithelial cells and is presumed to
      facilitate the process of colonization. Additionally, Hap mediates adherence to
      fibronectin, laminin and collagen IV, extracellular matrix (ECM) proteins that
      are present in the respiratory tract and are probably important targets for H.
      influenzae colonization. The region of Hap responsible for adherence to ECM
      proteins has been localized to the C-terminal 511 aa of the Hap passenger domain
      (HapS). In this study, we characterized the structural determinants of the
      interaction between HapS and fibronectin. Using defined fibronectin fragments, we
      established that Hap interacts with the fibronectin repeat fragment called
      FNIII(1-2). Using site-directed mutagenesis, we found a series of motifs in the C
      terminal region of HapS that contribute to the interaction with fibronectin. Most
      of these motifs are located on the F1 and F3 faces of the HapS structure,
      suggesting that the F1 and F3 faces may be responsible for the HapS-fibronectin
      interaction. 

PMID- 24687949
TI  - Prevalence of IncI1-Igamma and IncFIA-FIB type plasmids in extended-spectrum beta
      lactamase-producing Klebsiella pneumoniae strains isolated from the NICU of a
      North Indian hospital.
AB  - We studied the molecular mechanism of resistance in extended-spectrum beta
      lactamase (ESBL)-producing Klebsiella pneumoniae isolated from a neonatal
      intensive care unit (NICU) of one of the hospitals in North India. A total of
      3000 clinical samples were collected from a NICU (January 2009 to February 2011),
      of which 523 strains were K. pneumoniae positive and 262 of them were ESBL
      producing K. pneumoniae strains. All of the ESBL-producing clinical isolates were
      susceptible to carbapenems. However, the majority of the clinical isolates (30-96
      %) were resistant to a wide range of antibiotics including antibiotic/inhibitor
      combinations. The MIC values confirmed that these isolates were highly resistant
      to cephalosporins and aztreonam. In the 262 ESBL-producing K. pneumoniae
      isolates, 15 different enterobacterial repetitive intergenic consensus (ERIC)-PCR
      typed phylogenetic groups were identified and reconfirmed by PFGE.
      Characterization of plasmids from each representative member of these
      phylogenetic groups revealed the presence of three plasmids of different sizes.
      Conjugation experiments confirmed the presence of different resistance markers
      only on the 154 kb plasmid. PCR amplification and sequence analysis revealed that
      blaCTX-M-3, blaTEM-1, blaSHV-1, blaOXA-1 and armA were the predominant resistance
      markers. Plasmid-replicon typing showed that IncI1-Igamma and IncFIA-FIB types
      are the most prevalent. This study shows the co-existence of multiple ESBL
      encoding genes and their polyclonal dissemination among K. pneumoniae clinical
      isolates in the NICU of a North Indian hospital. 

PMID- 24687950
TI  - Strategy for modeling flow diverters in cerebral aneurysms as a porous medium.
AB  - Simulations using the patient-specific geometry of the aneurysm may help in a
      better planning of the treatment and in a consequent reduction of the associated
      risks. We propose, evaluate, and implement a methodology for the simulation of
      flow diverter (FD) devices in intracranial aneurysms by using a porous medium
      method (PMM), which greatly reduces the computational cost of these simulations
      compared with immersed method (IMM) approaches used to model complex FDs. The
      method relies on parameters from an empirical correlation derived from
      experimental observations in wire screens, consistent with CFD simulations. The
      verification of our PMM strategy was carried out by comparing the results of
      simulations in different (patient-specific) geometries and FDs, to those obtained
      under identical conditions by the IMM. Overall, both quantitative and qualitative
      results are consistent between IMM and PMM in cases where the local porosity
      remains roughly uniform throughout the neck, with differences in the reduction of
      the observables lower than 10%. This PMM strategy is up to 10 times faster than
      the IMM, which allows for a runtime of hours instead of days, bringing it closer
      for its application in the clinic.

PMID- 24687952
TI  - Mutant p53 accumulation in human breast cancer is not an intrinsic property or
      dependent on structural or functional disruption but is regulated by exogenous
      stress and receptor status.
AB  - Many human cancers contain missense TP53 mutations that result in p53 protein
      accumulation. Although generally considered as a single class of mutations that
      abrogate wild-type function, individual TP53 mutations may have specific
      properties and prognostic effects. Tumours that contain missense TP53 mutations
      show variable p53 stabilization patterns, which may reflect the specific mutation
      and/or aspects of tumour biology. We used immunohistochemistry on cell lines and
      human breast cancers with known TP53 missense mutations and assessed the effects
      of each mutation with four structure-function prediction methods. Cell lines with
      missense TP53 mutations show variable percentages of cells with p53 stabilization
      under normal growth conditions, ranging from approximately 50% to almost 100%.
      Stabilization is not related to structural or functional disruption, but agents
      that stabilize wild-type p53 increase the percentages of cells showing missense
      mutant p53 accumulation in cell lines with heterogeneous stabilization. The same
      heterogeneity of p53 stabilization occurs in primary breast cancers, independent
      of the effect of the mutation on structural properties or functional disruption.
      Heterogeneous accumulation is more common in steroid receptor-positive or HER2
      positive breast cancers and cell lines than in triple-negative samples.
      Immunohistochemcal staining patterns associate with Mdm2 levels, proliferation,
      grade and overall survival, whilst the type of mutation reflects downstream
      target activity. Inhibiting Mdm2 activity increases the extent of p53
      stabilization in some, but not all, breast cancer cell lines. The data indicate
      that missense mutant p53 stabilization is a complex and variable process in human
      breast cancers that associates with disease characteristics but is unrelated to
      structural or functional properties. That agents which stabilize wild-type p53
      also stabilize mutant p53 has implications for patients with heterogeneous mutant
      p53 accumulation, where therapy may activate mutant p53 oncogenic function.

PMID- 24687953
TI  - Evaluation of the HerpeSelect Express rapid test in the detection of herpes
      simplex virus type 2 antibodies in patients with genital ulcer disease.
AB  - BACKGROUND: A rapid point-of-care test with high sensitivity and specificity is
      required in order to fulfill the need for early detection and screening of Herpes
      simplex virus type 2 (HSV-2) infection among patients with genital ulcer disease
      (GUD), for better management and control of virus transmission. METHODS: The goal
      of this study is to evaluate the performance of the commercially available
      HerpeSelect Express rapid test in comparison with three ELISA assays: HerpeSelect
      ELISA, Kalon HSV-2 glycoprotein G2 assay, and monoclonal antibody blocking enzyme
      immunoassay, which was used as the gold standard for the detection of HSV-2
      antibodies. RESULTS: This study showed high sensitivity (ranging from 82.6 to
      100%) and specificity (100%) of the HerpeSelect Express rapid test when compared
      to the three ELISA assays. The agreement between the HerpeSelect Express rapid
      test with the three ELISAs ranged from 93.3 to 100%. CONCLUSION: The HerpeSelect
      Express rapid test has adequate sensitivity and specificity for confirming HSV-2
      infection in patients with GUD, indicating its suitability for epidemiological
      studies.

PMID- 24687954
TI  - Immediate effects of talocrural and subtalar joint mobilization on balance in the
      elderly.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to evaluate the
      immediate effects of therapeutic mobilization of the talocrural and subtalar
      joints on ankle mobility and postural control in elderly subjects. METHODS:
      Nineteen subjects (83.1 +/- 6 years, 159 +/- 1 cm; 56.1 +/- 9.7 kg - mean +/-
      standard deviation) participated in this study. The centre of pressure (COP)
      displacements along the anterior-posterior and medial-lateral axes was recorded
      in static and dynamic conditions on a force platform before and after therapeutic
      mobilization of the feet and ankles without blinding the subjects. RESULTS: In
      static conditions, the sway area is reduced contrarily to dynamic conditions
      where the sway area is increased. In the two experimental sessions, subjects
      showed comparable COP displacements and the total length of the oscillations.
      Results demonstrated a significant improvement immediately after mobilization for
      ankle range of motion in dorsal flexion (right +4.7 degrees ; left +3.2 degrees )
      and plantar flexion (right 5.2 degrees ; left +4.2 degrees ). CONCLUSION: These
      results suggested that postural control is improved in static conditions and
      decreased in dynamic conditions. Therapeutic mobilization of feet and ankles in
      the elderly provides an immediate improvement in joint range of movement in
      dorsal and plantar flexion.

PMID- 24687951
TI  - Measurements for 8 common analytes in native sera identify inadequate
      standardization among 6 routine laboratory assays.
AB  - BACKGROUND: External quality assessment (EQA) with commutable samples is
      essential for assessing the quality of assays performed by laboratories,
      particularly when the emphasis is on their standardization status and
      interchangeability of results. METHODS: We used a panel of 20 fresh-frozen single
      donation serum samples to assess assays for the measurement of creatinine,
      glucose, phosphate, uric acid, total cholesterol, HDL cholesterol, LDL
      cholesterol, and triglycerides. The commercial random access platforms included:
      Abbott Architect, Beckman Coulter AU, Ortho Vitros, Roche Cobas, Siemens Advia,
      and Thermo Scientific Konelab. The assessment was done at the peer group level
      and by comparison against the all-method trimmed mean or reference method values,
      where available. The considered quality indicators were intraassay imprecision,
      combined imprecision (including sample-matrix interference), bias, and total
      error. Fail/pass decisions were based on limits reflecting state-of-the-art
      performance, but also limits related to biological variation. RESULTS: Most
      assays showed excellent peer performance attributes, except for HDL- and LDL
      cholesterol. Cases in which individual assays had biases exceeding the used
      limits were the Siemens Advia creatinine (-4.2%), Ortho Vitros phosphate (8.9%),
      Beckman Coulter AU triglycerides (5.4%), and Thermo Scientific Konelab uric acid
      (6.4%), which lead to considerable interassay discrepancies. Additionally, large
      laboratory effects were observed that caused interlaboratory differences of >30%.
      CONCLUSIONS: The design of the EQA study was well suited for monitoring different
      quality attributes of assays performed in daily laboratory practice. There is a
      need for improvement, even for simple clinical chemistry analytes. In particular,
      the interchangeability of results remains jeopardized both by assay
      standardization issues and individual laboratory effects.

PMID- 24687955
TI  - Desirability function approach for the optimization of an in-syringe ultrasound
      assisted emulsification-microextraction method for the simultaneous determination
      of amlodipine and nifedipine in plasma samples.
AB  - In the present study, an in-syringe ultrasound-assisted emulsification
      microextraction using a low-density organic solvent was developed for
      simultaneous extraction and pre-concentration of amlodipine besylate and
      nifedipine from plasma samples. The extracts were analyzed by high-performance
      liquid chromatography with UV detection. Central composite design combined with
      desirability function was applied to find out the optimal experimental conditions
      providing the highest global extraction efficiency. The optimal conditions
      identified were volume of the extracting solvent 45 MUL, ionic strength 18.95%
      w/v, sonication time 2.58 min, and centrifugation time 3 min. Under the optimal
      conditions, the proposed method was evaluated, and applied to the analysis of
      amlodipine besylate and nifedipine in plasma samples. The validation results of
      the method indicated a wide linear range (2-1200 ng/mL) with a good linearity
      (r(2) >0.9991) and low detection limits (0.17 ng/mL for amlodipine besylate and
      0.15 ng/mL for nifedipine) with RSD less than 5.2% for both components, both in
      intra- and inter-day precision studies. The applicability of the proposed in
      syringe ultrasound-assisted emulsification-microextraction coupled to high
      performance liquid chromatography with UV detection method was demonstrated by
      analyzing the drugs in spiked plasma samples. 

PMID- 24687956
TI  - Compartmental endoscopic surgical anatomy of the medial intraconal orbital space.
AB  - BACKGROUND: Surgical management of intraconal pathology represents the next
      frontier in endoscopic endonasal surgery. Despite this, the medial intraconal
      space remains a relatively unexplored region, secondary to its variable and
      technically demanding anatomy. The purpose of this study is to define the
      neurovascular structures in this region and introduce a compartmentalized
      approach to enhance surgical planning. METHODS: This study was an institutional
      review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After
      dissection of the medial intraconal space, the pattern and trajectory of the
      oculomotor nerve and ophthalmic arterial arborizations were analyzed. The
      position of all vessels as well as the length of the oculomotor trunk and
      branches relative to the sphenoid face were calculated. RESULTS: A mean of 1.5
      arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from
      the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted
      adjacent to the midline of medial rectus. The oculomotor nerve inserted at the
      level of the sphenoid face and arborized with a large proximal trunk 5.5 +/- 1.1
      mm in length and multiple branches extending 13.2 +/- 2.7 mm from the sphenoid
      face. The most anterior nerve and vascular pedicle were identified at 17.0 and
      15.0 mm from the sphenoid face, respectively. CONCLUSION: The neurovascular
      supply to the medial rectus muscle describes a varied but predictable pattern.
      This data allows the compartmentalization of the medial intraconal space into 3
      zones relative to the neurovascular supply. These zones inform the complexity of
      the dissection and provide a guideline for safe medial rectus retraction relative
      to the fixed landmark of the sphenoid face.

PMID- 24687957
TI  - Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in
      cancer immunotherapy.
AB  - Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody
      yields durable responses in a subset of cancer patients and has been approved by
      the FDA as a standard therapy for late-stage melanoma. We recently identified
      inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of
      CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement
      by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor
      immune responses in both quantity and quality and significantly improved
      rejection of established melanoma and prostate cancer in mice. This study
      provides strong support for the development of combinatorial therapies
      incorporating anti-CTLA-4 and ICOS engagement. 

PMID- 24687958
TI  - EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase
      Cgamma, Ca++, and Erk, leading to granule polarization.
AB  - Ewing's sarcoma-associated transcript 2 (EAT-2) is an Src homology 2 domain
      containing intracellular adaptor related to signaling lymphocytic activation
      molecule (SLAM)-associated protein (SAP), the X-linked lymphoproliferative gene
      product. Both EAT-2 and SAP are expressed in natural killer (NK) cells, and their
      combined expression is essential for NK cells to kill abnormal hematopoietic
      cells. SAP mediates this function by coupling SLAM family receptors to the
      protein tyrosine kinase Fyn and the exchange factor Vav, thereby promoting
      conjugate formation between NK cells and target cells. We used a variety of
      genetic, biochemical, and imaging approaches to define the molecular and cellular
      mechanisms by which EAT-2 controls NK cell activation. We found that EAT-2
      mediates its effects in NK cells by linking SLAM family receptors to
      phospholipase Cgamma, calcium fluxes, and Erk kinase. These signals are triggered
      by one or two tyrosines located in the carboxyl-terminal tail of EAT-2 but not
      found in SAP. Unlike SAP, EAT-2 does not enhance conjugate formation. Rather, it
      accelerates polarization and exocytosis of cytotoxic granules toward
      hematopoietic target cells. Hence, EAT-2 promotes NK cell activation by molecular
      and cellular mechanisms distinct from those of SAP. These findings explain the
      cooperative and essential function of these two adaptors in NK cell activation. 

PMID- 24687959
TI  - CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and
      maintenance of gut CD4+ Th17 during parasitic infection.
AB  - Retention of lymphocytes in the intestinal mucosa requires specialized chemokine
      receptors and adhesion molecules. We find that both CD4(+)CD8(+) and CD4(+) T
      cells in the intestinal epithelium, as well as CD8(+) T cells in the intestinal
      mucosa and mesenteric lymph nodes, express the cell adhesion molecule class I
      restricted T cell-associated molecule (Crtam) upon activation, whereas the ligand
      of Crtam, cell adhesion molecule 1 (Cadm1), is expressed on gut CD103(+)DCs. Lack
      of Crtam-Cadm1 interactions in Crtam(-/-) and Cadm1(-/-) mice results in loss of
      CD4(+)CD8(+) T cells, which arise from mucosal CD4(+) T cells that acquire a CD8
      lineage expression profile. After acute oral infection with Toxoplasma gondii,
      both WT and Crtam(-/-) mice mounted a robust TH1 response, but markedly fewer
      TH17 cells were present in the intestinal mucosa of Crtam(-/-) mice. The almost
      exclusive TH1 response in Crtam(-/-) mice resulted in more efficient control of
      intestinal T. gondii infection. Thus, Crtam-Cadm1 interactions have a major
      impact on the residency and maintenance of CD4(+)CD8(+) T cells in the gut mucosa
      in the steady state. During pathogenic infection, Crtam-Cadm1 interactions
      regulate the dynamic equilibrium between newly formed CD4(+) T cells and their
      retention in the gut, thereby shaping representation of disparate CD4(+) T cell
      subsets and the overall quality of the CD4(+) T cell response. 

PMID- 24687961
TI  - Complexities associated with the molecular and proteomic identification of
      Paecilomyces species in the clinical mycology laboratory.
AB  - Paecilomyces species are emerging fungal pathogens. Morphological identifications
      are complicated by similarities among the members of the P. variotii complex as
      well as to some Rasamsonia and Hamigera species. The purpose of this study was to
      compare matrix-assisted laser desorption ionization-time-of-flight mass
      spectrometry (MALDI-TOF MS) with molecular diagnostic standards (i.e., multilocus
      DNA sequencing of the internal transcribed spacer regions 1 and 2, D1/D2 regions,
      and part of the beta-tubulin gene) for the identification of Paecilomyces spp.
      encountered in two clinical mycology laboratories. A total of 77 clinical
      isolates identified morphologically as P. variotii (n = 21), P. lilacinus (n =
      52), and Paecilomyces spp. not otherwise specified (n = 4) were included. In
      accord with the most recent taxonomy, all P. lilacinus isolates were confirmed as
      Purpureocillium lilacinum by both sequencing and MALDI-TOF MS. Fungi
      phenotypically resembling P. variotii or Paecilomyces spp. were identified by
      molecular techniques as P. variotii sensu stricto (n = 12), P. formosus (n = 3),
      P. dactylethromorphus (n = 3), Rasamsonia argillacea (n = 4), or R. piperina (n =
      1) and at the genus level as an isolate of a Hamigera sp. and a Paecilomyces sp.
      There was 92.2% (71/77) agreement between the molecular and proteomic methods
      only after supplementation of the MALDI-TOF MS database with type strains.
      Paecilomyces variotii-like organisms required multilocus DNA interrogations for
      differentiation and account for all of the fungi whose identification was missed
      by MALDI-TOF MS. Overall, MALDI-TOF MS was a rapid and reliable alternative to
      multilocus sequencing. However, significant augmentation of the commercially
      available database was required to reproducibly identify this group of important
      human pathogens. 

PMID- 24687960
TI  - Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine
      thymocyte progenitors with multipotent potential.
AB  - Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) exhibits lymphoid,
      myeloid, and stem cell features and is associated with a poor prognosis. Whole
      genome sequencing of human ETP-ALL cases has identified recurrent mutations in
      signaling, histone modification, and hematopoietic development genes but it
      remains to be determined which of these abnormalities are sufficient to initiate
      leukemia. We show that activating mutations in the interleukin-7 receptor
      identified in human pediatric ETP-ALL cases are sufficient to generate ETP-ALL in
      mice transplanted with primitive transduced thymocytes from p19(Arf-/-) mice. The
      cellular mechanism by which these mutant receptors induce ETP-ALL is the block of
      thymocyte differentiation at the double negative 2 stage at which myeloid lineage
      and T lymphocyte developmental potential coexist. Analyses of samples from
      pediatric ETP-ALL cases and our murine ETP-ALL model show uniformly high levels
      of LMO2 expression, very low to undetectable levels of BCL11B expression, and a
      relative lack of activating NOTCH1 mutations. We report that pharmacological
      blockade of Jak-Stat signaling with ruxolitinib has significant antileukemic
      activity in this ETP-ALL model. This new murine model recapitulates several
      important cellular and molecular features of ETP-ALL and should be useful to
      further define novel therapeutic approaches for this aggressive leukemia. 

PMID- 24687962
TI  - Ageing and dementia in a longitudinal study of a cohort with Down syndrome.
AB  - BACKGROUND: A population sample of people with Down syndrome has been studied
      from infancy and has now been followed up again at age 47 years. METHODS:
      Intelligence and language skills were tested and daily living skills assessed.
      Memory/cognitive deterioration was examined using two test instruments. RESULTS:
      Scores on verbal tests of intelligence changed little. Those on a non-verbal
      test, on self-help skills and on both memory tests showed some decline, even when
      the scores of those already suffering from dementia were discounted. CONCLUSIONS:
      At age 47, scores on most tests of even the majority of the cohort (i.e. those
      not definitely diagnosed with dementia) showed some decline. While this includes
      the scores of people who may subsequently develop dementia, it may also reflect
      the normal ageing process in this population.

PMID- 24687963
TI  - Second-generation cryoballoon ablation for paroxysmal atrial fibrillation: a step
      forward?

PMID- 24687964
TI  - The budget impact of left atrial appendage closure compared with adjusted-dose
      warfarin and dabigatran etexilate for stroke prevention in atrial fibrillation.
AB  - AIMS: Major practice changes require both clinical and economic rationale,
      especially where a novel device replaces an established pharmaceutical therapy.
      Recent studies have reported the clinical benefits of percutaneous left atrial
      appendage closure (LAAC) for stroke prevention in atrial fibrillation (AF)
      relative to standard warfarin anticoagulation, but little is published on the
      cost implications of LAAC. This analysis sought to quantify the budget impact of
      LAAC compared with warfarin and dabigatran etexilate for stroke prevention in AF.
      METHODS AND RESULTS: A budget impact model was constructed from a German payer
      perspective across a 10-year time horizon. Clinical event probabilities were
      taken from the PROTECT AF and RE-LY clinical studies. Clinical events included
      stroke, major extracranial bleeding, systemic embolism, procedure-related
      complications, and death. Costs for stroke included acute, direct costs, as well
      as long-term disability costs. Cost inputs were taken from German inpatient
      diagnosis related groups (DRGs), German pharmaceutical pricing databases, and the
      literature. The findings from this model suggest that LAAC provides long-term
      clinical and economic benefit while also reducing overall mortality. At 8 years,
      LAAC was less expensive than dabigatran (?15 061 vs. ?16 184), and at 10 years,
      it was only 10% more expensive than warfarin (?16 736 vs. ?15 168). CONCLUSION:
      The majority of LAAC costs are borne in the first year, while costs for
      pharmaceutical strategies continue to accrue year on year. Thus, LAAC represents
      an opportunity for savings to healthcare systems in the long term. This is an
      important consideration for payers in evaluating lifetime treatment strategies in
      AF.

PMID- 24687965
TI  - Left and right ventricular lead positions are imprecisely determined by
      fluoroscopy in cardiac resynchronization therapy: a comparison with cardiac
      computed tomography.
AB  - AIMS: Fluoroscopy is the routine method for localizing left ventricular (LV) and
      right ventricular (RV) lead positions in cardiac resynchronization therapy (CRT).
      However, the ability of fluoroscopy to determine lead positions in a standard
      ventricular segmentation is unknown. We aimed to evaluate the accuracy and
      reproducibility of fluoroscopy to determine LV and RV lead positions in CRT when
      compared with cardiac computed tomography (CT). METHODS AND RESULTS: Fifty-nine
      patients undergoing CRT were included. Bi-plane fluoroscopy and cardiac CT were
      evaluated in all patients. Pacing lead positions were assessed in a standard LV
      16-segment model and in a simplistic RV 8-segment model. Four patients with LV
      lead displacement were excluded from the agreement analysis of LV lead position.
      Agreement of LV lead position between fluoroscopy and cardiac CT was observed in
      19 (35%) patients with fluoroscopy demonstrating a 1-segment and >=2-segment
      error in 30 (55%) and 6 (11%) patients, respectively. Agreement of RV lead
      position was found in 13 (22%) patients with fluoroscopy showing a 1-segment and
      >= 2-segment error in 28 (47%) and 18 (31%) patients, respectively. The
      interobserver agreement on LV and RV lead positions was poor for fluoroscopy
      (kappa 0.20 and 0.23, respectively) and excellent for cardiac CT (kappa 0.87 and
      0.85, respectively). CONCLUSION: Fluoroscopy is inaccurate and modestly
      reproducible when assessing LV and RV lead positions in a standard ventricular
      segmentation when compared with cardiac CT. Cardiac CT should be applied to
      determine the exact pacing site in future research evaluating the optimal pacing
      lead position in CRT.

PMID- 24687966
TI  - Prematurity Reduces Functional Adaptation to Intestinal Resection in Piglets.
AB  - BACKGROUND: Necrotizing enterocolitis and congenital gastrointestinal
      malformations in infants often require intestinal resection, with a subsequent
      risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal
      adaptation following resection of the distal intestine with placement of a
      jejunostomy differs between preterm and term neonates. METHODS: Preterm or term
      piglets were born by cesarean section and fed enterally for 2 days. On day 2,
      piglets were subjected to 50% distal intestinal resection with placement of a
      jejunostomy. On the following 4-5 days, piglets received parenteral nutrition
      with gradually increasing doses of enteral nutrition (bovine colostrum).
      Intestinal tissue samples were collected at delivery and 2 and 6-7 days after
      birth for histological examination and assessment of digestive enzyme activities.
      RESULTS: Preterm and term piglets showed similar increases in intestinal weight
      and digestive enzyme activities from birth to 2 days. On days 6-7 after birth,
      the remnant intestine showed a similar density (g/cm) and mucosal mass in term
      and preterm piglets, but villus height, crypt depth, enzyme activities (sucrase,
      maltase, dipeptidyl peptidase IV [DPPIV]), and hexose uptake capacity were
      significantly higher in term piglets (P < .05). Preterm piglets were more prone
      to develop hypoglycemia, respiratory distress syndrome, dehydration, and
      circulatory instability after surgery compared with term piglets. CONCLUSION:
      Studies on intestinal adaptation after resection are feasible in both preterm and
      term piglets, but intensive clinical support is required when rearing preterm
      piglets with SBS. Physiological instability and immaturity of the intestine may
      explain the fact that immediate adaptation after resection is reduced in preterm
      vs term neonates.

PMID- 24687967
TI  - National Trends and In-Hospital Outcomes of Adult Patients With Inflammatory
      Bowel Disease Receiving Parenteral Nutrition Support.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD), including Crohn's
      disease (CD) and ulcerative colitis (UC), are susceptible to protein-calorie
      malnutrition secondary to decreased oral intake, malabsorption, and increased
      metabolic expenditure. In this study, we seek to assess the national frequencies
      of parenteral nutrition (PN) use among hospitalized patients with IBD and to
      determine their in-hospital outcomes. METHODS: We analyzed the Nationwide
      Inpatient Sample from 1988-2006 to determine the frequency of PN usage among
      patients with UC or CD and to determine their in-hospital outcomes. A
      multivariate analysis was performed to identify factors predictive of increased
      inpatient mortality in this population. RESULTS: From 1988-2006, the annual
      incidence of PN use among hospitalized patients with CD was 4.29 per 100,000 and
      among those with UC was 3.80 per 100,000, with trends being relatively stable
      through the indexed period. The mean length of hospitalization among patients
      with UC receiving PN was longer compared with patients with CD. Factors
      predictive of an increased risk for mortality include the following: age >50
      years, acute kidney injury, hospital-acquired pneumonia, Clostridium difficile
      colitis, prolonged postoperative ileus requiring PN use, pulmonary embolism,
      malnutrition, and patients with UC relative to CD. CONCLUSION: Traditionally,
      patients with CD are at a higher risk for developing malnutrition than patients
      with UC; however, there is a 2-fold higher risk for inpatient mortality and a
      longer length of hospitalization among patients with UC compared with those with
      CD. This pattern suggests that the use of PN, particularly among patients with
      UC, serves as a surrogate marker of higher disease acuity and severity.

PMID- 24687968
TI  - Trace analysis of herbicides in wastewaters by a dispersive liquid-liquid
      microextraction approach and liquid chromatography with quadrupole linear ion
      trap mass spectrometry: evaluation of green parameters.
AB  - An analytical method for determining phenylureas (monuron, isoproturon, diuron,
      linuron and neburon) and propanil herbicides in wastewater has been developed and
      validated, and the most significant parameters were compared with the
      corresponding ones found in the literature, thus showing the method performance.
      The method involves pre-concentration by a simple, rapid, sensitive and low
      environmental toxicity temperature-controlled ionic liquid dispersive liquid
      liquid microextraction procedure. The herbicides were identified and determined
      by liquid chromatography with a hybrid triple quadrupole linear ion trap mass
      spectrometer. Data acquisition in selected-reaction monitoring mode allowed the
      simultaneous identification and quantification of the analytes using two
      transitions. The information dependent acquisition scan was performed to carry
      out the identification of those analytes whose second transition was present at
      low intensity, also providing extra confirmation for the other analytes. Limits
      of quantification were in the range 1.0-5.0 ng/L. Good recoveries (95-103%) were
      obtained for the extraction of the target analytes in wastewater samples. The
      methodology developed was applied to analyze effluent wastewater samples from a
      wastewater treatment plant located in an agricultural zone of Almeria (Spain) and
      the results indicated the presence of diuron at mean concentration levels of 73.5
      ng/L. 

PMID- 24687969
TI  - Exploiting the buccal mucosa as an alternative route for the delivery of
      donepezil hydrochloride.
AB  - The potential of the buccal mucosa as an alternative route for the systemic
      delivery of donepezil (DPZ) hydrochloride, and the impact of various skin
      penetration enhancers on DPZ buccal permeability, was assessed using an in vitro
      model. DPZ was applied to porcine buccal mucosa in modified Ussing chambers
      either alone (20 MUg/mL) or with different treatment protocols of various
      enhancers including Azone(r) (AZ), deoxycholic acid (DA), polyethylene glycol
      (PEG) 400, and oleic acid (OA)-PEG 400. DPZ permeated the buccal mucosa very
      rapidly with a permeability coefficient of 35.6 +/- 4.9 * 10(-6) cm/s, which was
      not significantly affected by AZ pretreatment. Coapplication of DA 0.6% (w/w),
      but not DA 0.01% (w/w), reduced the buccal permeation of DPZ (3.5-fold), and PEG
      400 reduced the absorption of DPZ in a dose-dependent manner (1.6- and 18.0-fold
      reduction at 5% and 50%, w/w, PEG 400, respectively). Coapplication of a
      combination of OA 1% (v/w) and PEG 400 5% (w/w) further reduced DPZ permeability
      (5.5-fold), which was demonstrated to result from excipient-induced DPZ
      precipitation as assessed by light microscopy analysis. These results confirm the
      feasibility of a novel buccal delivery system for Alzheimer's disease, and
      suggest various approaches that may be exploited for controlled buccal delivery
      of DPZ.

PMID- 24687971
TI  - Microwave-assisted preparation of poly(ionic liquids)-modified magnetic
      nanoparticles for pesticide extraction.
AB  - Novel poly(ionic liquids) were synthesized and immobilized on prepared magnetic
      nanoparticles, which were used to extract pesticides from fruit and vegetable
      samples by dispersive solid-phase extraction prior to high-performance liquid
      chromatography analysis. Compared with monomeric ionic liquids, poly(ionic
      liquids) have a larger effective contact area and higher viscosity, so they can
      achieve higher extraction efficiency and be used repeatedly without a decrease in
      analyte recovery. The immobilized poly(ionic liquids) were rapidly separated from
      the sample matrix, providing a simple approach for sample pretreatment. The
      nature and volume of the desorption solvent and amount of poly(ionic liquid)
      modified magnetic material were optimized for the extraction process. Under
      optimum conditions, calibration curves were linear (R(2) > 0.9988) for pesticide
      concentrations in the range of 0.100-10.000 MUg/L. The relative standard
      deviations for repeated determinations of the four analytes were 2.29-3.31%. The
      limits of detection and quantification were 0.29-0.88 and 0.97-2.93 MUg/L,
      respectively. Our results demonstrate that the developed poly(ionic liquid)
      modified material is an effective absorbent to extract pesticides from fruit and
      vegetable samples. 

PMID- 24687972
TI  - Hormonal contraception in female lung transplant recipients: a case series.

PMID- 24687970
TI  - HER2 and GATA4 are new prognostic factors for early-stage ovarian granulosa cell
      tumor-a long-term follow-up study.
AB  - Granulosa cell tumors (GCTs) carry a risk of recurrence also at an early stage,
      but reliable prognostic factors are lacking. We assessed clinicopathological
      prognostic factors and the prognostic roles of the human epidermal growth factor
      receptors (HER 2-4) and the transcription factor GATA4 in GCTs. We conducted a
      long-term follow-up study of 80 GCT patients with a mean follow-up time of 16.8
      years. A tumor-tissue microarray was immunohistochemically stained for HER2-4 and
      GATA4. Expression of HER2-4 mRNA was studied by means of real time polymerase
      chain reaction and HER2 gene amplification was analyzed by means of silver in
      situ hybridization. The results were correlated to clinical data on recurrences
      and survival. We found that GCTs have an indolent prognosis, with 5-year disease
      specific survival (DSS) being 97.5%. Tumor recurrence was detected in 24% of the
      patients at a median of 7.0 years (range 2.6-18 years) after diagnosis. Tumor
      stage was not prognostic of disease-free survival (DFS). Of the molecular
      prognostic factors, high-level expression of HER2, and GATA4, and high nuclear
      atypia were prognostic of shorter DFS. In multivariate analyses, high-level
      coexpression of HER2 and GATA4 independently predicted DFS (hazard ratio [HR]
      8.75, 95% CI 2.20-39.48, P = 0.002). High-level expression of GATA4 also
      predicted shorter DSS (HR 3.96, 95% CI 1.45-12.57, P = 0.006). In multivariate
      analyses, however, tumor stage (II-III) and nuclear atypia were independent
      prognostic factors of DSS. In conclusion HER2 and GATA4 are new molecular
      prognostic markers of GCT recurrence, which could be utilized to optimize the
      management and follow-up of patients with early-stage GCTs.

PMID- 24687973
TI  - Australasian nutrition research for prevention and management of child obesity:
      innovation and progress in the last decade.
AB  - BACKGROUND/OBJECTIVE: The Food and Nutrition stream of Australasian Child and
      Adolescent Obesity Research Network (ACAORN) aims to improve the quality of
      dietary methodologies and the reporting of dietary intake within Australasian
      child obesity research (http://www.acaorn.org.au/streams/nutrition/).
      METHODS/RESULTS: With 2012 marking ACAORN's 10th anniversary, this commentary
      profiles a selection of child obesity nutrition research published over the last
      decade by Food and Nutrition Stream members. In addition, stream activities have
      included the development of an online selection guide to assist researchers in
      their selection of appropriate dietary intake methodologies
      (http://www.acaorn.org.au/streams/nutrition/dietary-intake/index.php).
      CONCLUSIONS: The quantity and quality of research to guide effective child
      obesity prevention and treatment has increased substantially over the last
      decade. ACAORN provides a successful case study of how research networks can
      provide a collegial atmosphere to foster and coordinate research efforts in an
      otherwise competitive environment.

PMID- 24687974
TI  - Reversed-phase high-performance liquid chromatography method with fluorescence
      detection to screen nitric oxide synthases inhibitors.
AB  - Nitric oxide synthase (NOS) inhibitors are potential drug candidates due to the
      critical role of an excessive production of nitric oxide in a range of diseases.
      At present, the radiometric detection of L-[(3)H]-citrulline produced from L
      [(3)H]-arginine during the enzymatic reaction is one of the most accepted methods
      to assess the in vitro activity of NOS inhibitors. Here we report a fast, easy,
      and cheap reversed-phase high-performance liquid chromatography method with
      fluorescence detection, based on the precolumn derivatization of L-citrulline
      with o-phthaldialdehyde/N-acetyl cysteine, for the in vitro screening of NOS
      inhibitors. To evaluate enzyme inhibition by the developed method, N-[3
      (aminomethyl)benzyl]acetamidine, a potent and selective inhibitor of inducible
      NOS, was used as a test compound. The half maximal inhibitory concentration
      obtained was comparable to that derived by the well-established radiometric
      assay.

PMID- 24687975
TI  - The NIAID Integrated Research Facility at Frederick, Maryland: a unique
      international resource to facilitate medical countermeasure development for BSL-4
      pathogens.
AB  - Scientists at the National Institute of Allergy and Infectious Diseases
      Integrated Research Facility at Fort Detrick, Frederick, Maryland, coordinate and
      facilitate preclinical research on infectious diseases to develop medical
      countermeasures for high-consequence pathogens. This facility is unique in that
      it is the only maximum containment laboratory in the world where conventional and
      molecular medical imaging equipments are incorporated into the design of the
      facility. This capability provides investigators with unique tools to dissect
      disease pathogenesis, evaluate the ability of animal models to recapitulate human
      disease, and test candidate countermeasures. Importantly, advanced molecular
      imaging has the potential to provide alternative endpoints to lethality. Using
      these alternative endpoints, investigators can reduce the number of animals used
      in experiments and evaluate countermeasures in sublethal models. With the
      incorporation of medical imaging modalities, a clinical laboratory modeled after
      those existing in hospitals, and a highly trained veterinary medicine team, IRF
      Frederick is uniquely suited to advance our understanding of emerging infectious
      diseases and to facilitate the development of medical countermeasures and
      clinical care paradigms previously considered impossible. 

PMID- 24687976
TI  - Is capillary electrophoresis on microchip devices able to genotype uridine
      diphosphate glucuronosyltransferase 1A1 TATA-box polymorphisms?
AB  - In this commentary, we focused our attention on capillary electrophoresis. It
      achieves the efficient separation of molecular species by the application of high
      voltages to samples in solution. Actually, capillary electrophoresis can be
      performed on microchip devices, based on an automated and miniaturized
      electrophoresis system, based on lab-on-a-chip technology. By this technology it
      is possible to separate nucleic acid fragments (DNA or RNA) with respect to
      sizing accuracy and sizing resolution. Currently, two automated capillary
      electrophoresis on microchips devices are available: the Agilent 2100 Bioanalyzer
      and the ExperionTM Automated Electrophoresis System. In this study, we evaluated
      if the CE is able to distinguish the three uridine diphosphate
      glucuronosyltransferase 1A1 TATA-box genotypes. 

PMID- 24687977
TI  - Autophagy, plant senescence, and nutrient recycling.
AB  - Large numbers of publications have appeared over the last few years, dealing with
      the molecular details of the regulation and process of the autophagy machinery in
      animals, plants, and unicellular eukaryotic organisms. This strong interest is
      caused by the fact that the autophagic process is involved in the adaptation of
      organisms to their environment and to stressful conditions, thereby contributing
      to cell and organism survival and longevity. In plants, as in other eukaryotes,
      autophagy is associated with longevity as mutants display early and strong leaf
      senescence symptoms, however, the exact role of autophagy as a pro-survival or
      pro-death process is unclear. Recently, evidence that autophagy participates in
      nitrogen remobilization has been provided, but the duality of the role of
      autophagy in leaf longevity and/or nutrient recycling through cell component
      catabolism remains. This review aims to give an overview of leaf senescence
      associated processes from the physiological point of view and to discuss
      relationships between nutrient recycling, proteolysis, and autophagy. The dual
      role of autophagy as a pro-survival or pro-death process is discussed. 

PMID- 24687978
TI  - Synthetic biology approaches to engineering the nitrogen symbiosis in cereals.
AB  - Nitrogen is abundant in the earth's atmosphere but, unlike carbon, cannot be
      directly assimilated by plants. The limitation this places on plant productivity
      has been circumvented in contemporary agriculture through the production and
      application of chemical fertilizers. The chemical reduction of nitrogen for this
      purpose consumes large amounts of energy and the reactive nitrogen released into
      the environment as a result of fertilizer application leads to greenhouse gas
      emissions, as well as widespread eutrophication of aquatic ecosystems. The
      environmental impacts are intensified by injudicious use of fertilizers in many
      parts of the world. Simultaneously, limitations in the production and supply of
      chemical fertilizers in other regions are leading to low agricultural
      productivity and malnutrition. Nitrogen can be directly fixed from the atmosphere
      by some bacteria and Archaea, which possess the enzyme nitrogenase. Some plant
      species, most notably legumes, have evolved close symbiotic associations with
      nitrogen-fixing bacteria. Engineering cereal crops with the capability to fix
      their own nitrogen could one day address the problems created by the over- and
      under-use of nitrogen fertilizers in agriculture. This could be achieved either
      by expression of a functional nitrogenase enzyme in the cells of the cereal crop
      or through transferring the capability to form a symbiotic association with
      nitrogen-fixing bacteria. While potentially transformative, these
      biotechnological approaches are challenging; however, with recent advances in
      synthetic biology they are viable long-term goals. This review discusses the
      possibility of these biotechnological solutions to the nitrogen problem, focusing
      on engineering the nitrogen symbiosis in cereals. 

PMID- 24687979
TI  - Requirement for A-type cyclin-dependent kinase and cyclins for the terminal
      division in the stomatal lineage of Arabidopsis.
AB  - The Arabidopsis stoma is a specialized epidermal valve made up of a pair of guard
      cells around a pore whose aperture controls gas exchange between the shoot and
      atmosphere. Guard cells (GCs) are produced by a symmetric division of guard
      mother cells (GMCs). The R2R3-MYB transcription factor FOUR LIPS (FLP) and its
      paralogue MYB88 restrict the division of a GMC to one. Previously, the upstream
      regions of several core cell cycle genes were identified as the direct targets of
      FLP/MYB88, including the B-type cyclin-dependent kinase CDKB1;1 and A2-type
      cyclin CYCA2;3. Here we show that CDKA;1 is also an immediate direct target of
      FLP/MYB88 through the binding to cis-regulatory elements in the CDKA;1 promoter
      region. CDKA;1 activity is required not only for normal GMC divisions but also
      for the excessive cell overproliferation in flp myb88 mutant GMCs. The impaired
      defects of GMC division in cdkb1;1 1;2 mutants could be partially rescued by a
      stage-specific expression of CDKA;1. Although targeted overexpression of CDKA;1
      does not affect stomatal development, ectopic expression of the D3-type cyclin
      CYCD3;2 induces GC subdivision, resulting in a stoma with 3-4 GCs instead of the
      normal two. Co-overexpression of CDKA;1 with CYCD3;2, but not with CYCA2;3,
      confers a synergistic effect with respect to GC subdivision. Thus, in addition to
      a role in stomatal formative asymmetric divisions at early developmental stages,
      CDKA;1 is needed in triggering GMC symmetric divisions at the late stage of
      stomatal development. However, timely down-regulation of CDKA;1-CYCD3 activity is
      required for restriction of GC proliferation. 

PMID- 24687980
TI  - Exploiting transplastomically modified Rubisco to rapidly measure natural
      diversity in its carbon isotope discrimination using tuneable diode laser
      spectroscopy.
AB  - Carbon isotope discrimination (Delta) during C3 photosynthesis is dominated by
      the fractionation occurring during CO2-fixation by the enzyme Rubisco. While
      knowing the fractionation by enzymes is pivotal to fully understanding plant
      carbon metabolism, little is known about variation in the discrimination factor
      of Rubisco (b) as it is difficult to measure using existing in vitro
      methodologies. Tuneable diode laser absorption spectroscopy has improved the
      ability to make rapid measurements of Delta concurrently with photosynthetic gas
      exchange. This study used this technique to estimate b in vivo in five tobacco
      (Nicotiana tabacum L. cv Petit Havana [N,N]) genotypes expressing alternative
      Rubisco isoforms. For transplastomic tobacco producing Rhodospirillum rubrum
      Rubisco b was 23.8+/-0.70/00, while Rubisco containing the large subunit Leu-335
      Val mutation had a b-value of 13.9+/-0.70/00. These values were significantly
      less than that for Rubisco from wild-type tobacco (b=290/00), a C3 species.
      Transplastomic tobacco producing chimeric Rubisco comprising tobacco Rubisco
      small subunits and the catalytic large subunits from either the C4 species
      Flaveria bidentis or the C3-C4 species Flaveria floridana had b-values of 27.8+/
      0.8 and 28.6+/-0.60/00, respectively. These values were not significantly
      different from tobacco Rubisco. 

PMID- 24687982
TI  - Faulty needle-tips: are they a clinical hazard?

PMID- 24687984
TI  - Editor's response to 'Just to be sure'.

PMID- 24687987
TI  - Application of thermodynamic-based retention time prediction to ionic liquid
      stationary phases.
AB  - First- and second-dimension retention times for a series of alkyl phosphates were
      predicted for multiple column combinations in GC*GC. This was accomplished
      through the use of a three-parameter thermodynamic model where the analytes'
      interactions with the stationary phases in both dimensions are known. Ionic
      liquid columns were employed to impart unique selectivity for alkyl phosphates,
      and it was determined that for alkyl phosphate compounds, ionic liquid columns
      are best used in the primary dimension. Retention coordinates for unknown
      phosphates are predicted from the thermodynamic parameters of a set standard
      alkyl phosphates. Additionally, we present changing retention properties of alkyl
      phosphates on some ionic liquid columns, due to suspected reaction between the
      analyte and column. This makes it difficult to accurately predict their retention
      properties, and in general poses a problem for ionic liquid columns with these
      types of analytes. 

PMID- 24687986
TI  - Genetic control of weight loss during pneumonic Burkholderia pseudomallei
      infection.
AB  - Burkholderia pseudomallei (Bp) is the causal agent of a high-morbidity/mortality
      disease syndrome known as melioidosis. This syndrome can range from acute
      fulminate disease to chronic, local, and disseminated infections that are often
      difficult to treat because Bp exhibits resistance to many antibiotics. Bp is a
      prime candidate for use in biologic warfare/terrorism and is classified as a Tier
      1 select agent by HHS and APHIS. It is known that inbred mouse strains display a
      range of susceptibility to Bp and that the murine infection model is ideal for
      studying acute melioidosis. Here, we exploit a powerful mouse genetics resource
      that consists of a large family of BXD-type recombinant inbred strains, to
      perform genome-wide linkage analysis of the weight loss phenotype following
      pneumonic infection with Bp. We infected parental mice and 32 BXD strains with 50
      100 CFU of Bp (strain 1026b) and monitored weight retention each day over an
      eleven-day time course. Using the computational tools in GeneNetwork, we
      performed genome-wide linkage analysis to identify an interval on chromosome 12
      that appears to control the weight retention trait. We then analyzed and ranked
      positional candidate genes in this interval, several of which have intriguing
      connections with innate immunity, calcium homeostasis, lipid transport, host cell
      growth and development, and autophagy. 

PMID- 24687988
TI  - Oral immunization with recombinant Lactococcus lactis delivering a multi-epitope
      antigen CTB-UE attenuates Helicobacter pylori infection in mice.
AB  - Urease is an essential virulence factor and colonization factor for Helicobacter
      pylori (H. pylori) and is considered as an excellent vaccine candidate antigen.
      However, conventional technologies for preparing an injectable vaccine require
      purification of the antigenic protein and preparation of an adjuvant. Lactococcus
      lactis NZ9000 (L. lactis) could serve as an antigen-delivering vehicle for the
      development of edible vaccine. In previous study, we constructed a multi-epitope
      vaccine, designated CTB-UE, which is composed of the mucosal adjuvant cholera
      toxin B subunit (CTB), three Th cell epitopes and two B-cell epitopes from urease
      subunits. To develop a novel type of oral vaccine against H. pylori, genetically
      modified L. lactis strains were established to secrete this epitope vaccine
      extracellularly in this study. Oral prophylactic immunization with recombinant L.
      lactis significantly elicited humoral anti-urease antibody responses (P < 0.001)
      and reduced the gastric colonization of H. pylori from 7.14 +/- 0.95 to 4.68 +/-
      0.98 log10 CFU g(-1) stomach. This L. lactis oral vaccine offers a promising
      vaccine candidate for the control of H. pylori infection.

PMID- 24687989
TI  - Proteomic characterization of human proinflammatory M1 and anti-inflammatory M2
      macrophages and their response to Candida albicans.
AB  - In response to different stimuli, macrophages can differentiate into either a pro
      inflammatory subtype (M1, classically activated macrophages) or acquire an anti
      inflammatory phenotype (M2, alternatively activated macrophages). Candida
      albicans is the most important opportunistic fungus in nosocomial infections, and
      it is contended by neutrophils and macrophages during the first steps of the
      invasive infection. Murine macrophages responses to C. albicans have been widely
      studied, whereas the responses of human-polarized macrophages remain less
      characterized. In this study, we have characterized the proteomic differences
      between human M1- and M2-polarized macrophages, both in basal conditions and in
      response to C. albicans, by quantitative proteomics (2DE). This proteomic
      approach allowed us to identify metabolic routes and cytoskeletal rearrangement
      components that are the most relevant differences between M1 and M2 macrophages.
      The analysis has revealed fructose-1,6-bisphosphatase 1, a critical enzyme in
      gluconeogenesis, up-regulated in M1, as a novel protein marker for macrophage
      polarization. Regarding the response to C. albicans, an M1-to-M2 switch in
      polarization was observed. This M1-to-M2 switch might contribute to Candida
      pathogenicity by decreasing the generation of specific immune responses, thus
      enhancing fungal survival and colonization, or instead, may be part of the host
      attempt to reduce the inflammation and limit the damage of the infection. 

PMID- 24687990
TI  - Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte
      action potential and mild conduction system expansion but does not alter
      conduction system function or promote spontaneous arrhythmias.
AB  - CHF1/Hey2 is a Notch-responsive basic helix-loop-helix transcription factor
      involved in cardiac development. Common variants in Hey2 are associated with
      Brugada syndrome. We hypothesized that absence of CHF1/Hey2 would result in
      abnormal cellular electrical activity, altered cardiac conduction system (CCS)
      development, and increased arrhythmogenesis. We isolated neonatal CHF/Hey2
      knockout (KO) cardiac myocytes and measured action potentials and ion channel
      subunit gene expression. We also crossed myocardial-specific CHF1/Hey2-KO mice
      with cardiac conduction system LacZ reporter mice and stained for conduction
      system tissue. We also performed ambulatory ECG monitoring for arrhythmias and
      heart rate variability. Neonatal cardiomyocytes from CHF1/Hey2-KO mice
      demonstrate a 50% reduction in action potential dV/dT, a 50-75% reduction in
      SCN5A, KCNJ2, and CACNA1C ion channel subunit gene expression, and an increase in
      delayed afterdepolarizations from 0/min to 12/min. CHF1/Hey2 cKO CCS-lacZ mice
      have a ~3-fold increase in amount of CCS tissue. Ambulatory ECG monitoring showed
      no difference in cardiac conduction, arrhythmias, or heart rate variability. Wild
      type cells or animals were used in all experiments. CHF1/Hey2 may contribute to
      Brugada syndrome by influencing the expression of SCN5A and formation of the
      cardiac conduction system, but its absence does not cause baseline conduction
      defects or arrhythmias in the adult mouse.-Hartman, M. E., Liu, Y., Zhu, W.-Z.,
      Chien, W.-M., Weldy, C. S., Fishman, G. I., Laflamme, M. A., Chin, M. T.
      Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte
      action potential and mild conduction system expansion but does not alter
      conduction system function or promote spontaneous arrhythmias. 

PMID- 24687991
TI  - SIRT5 is under the control of PGC-1alpha and AMPK and is involved in regulation
      of mitochondrial energy metabolism.
AB  - The sirtuins (SIRTs; SIRT1-7) are a family of NAD(+)-dependent enzymes that
      dynamically regulate cellular physiology. Apart from SIRT1, the functions and
      regulatory mechanisms of the SIRTs are poorly defined. We explored regulation of
      the SIRT family by 2 energy metabolism-controlling factors: peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) and AMP
      activated protein kinase (AMPK). Overexpression of PGC-1alpha in mouse primary
      hepatocytes increased SIRT5 mRNA expression 4-fold and also the protein in a
      peroxisome proliferator-activated receptor alpha (PPARalpha)- and estrogen
      related receptor alpha (ERRalpha)-dependent manner. Furthermore, food withdrawal
      increased SIRT5 mRNA 1.3-fold in rat liver. Overexpression of AMPK in mouse
      hepatocytes increased expression of SIRT1, SIRT2, SIRT3, and SIRT6 <2-fold. In
      contrast, SIRT5 mRNA was down-regulated by 58%. The antidiabetes drug metformin
      (1 mM), an established AMPK activator, reduced the mouse SIRT5 protein level by
      44% in cultured hepatocytes and by 31% in liver in vivo (300 mg/kg, 7 d).
      Metformin also induced hypersuccinylation of mitochondrial proteins. Moreover,
      SIRT5 overexpression increased ATP synthesis and oxygen consumption in HepG2
      cells, but did not affect mitochondrial biogenesis. In summary, our results
      identified SIRT5 as a novel factor that controls mitochondrial function.
      Moreover, SIRT5 levels are regulated by PGC-1alpha and AMPK, which have opposite
      effects on its expression.-Buler, M., Aatsinki, S.-M., Izzi, V., Uusimaa, J.,
      Hakkola, J. SIRT5 is under the control of PGC-1alpha and AMPK and is involved in
      regulation of mitochondrial energy metabolism. 

PMID- 24687992
TI  - Microtubule dynamics at the growth cone are mediated by alpha7 nicotinic receptor
      activation of a Galphaq and IP3 receptor pathway.
AB  - The alpha7 nicotinic receptor (alpha7) plays an important role in neuronal growth
      and structural plasticity in the developing brain. We have recently characterized
      a G-protein-signaling pathway regulated by alpha7 that directs the growth of
      neurites in developing neural cells. Now we show that choline activation of
      alpha7 promotes a rise in intracellular calcium from local ER stores via Galphaq
      signaling, leading to IP3 receptor (IP3R) activation at the growth cone of
      differentiating PC12 cells. A mutant alpha7 significantly attenuated in calcium
      conductance (D44A; P<0.001) was found to be unable to promote IP3R signaling and
      calcium store release. In addition, calcium elevation via alpha7 correlates with
      a significant attenuation in the rate of microtubule invasion of the growth cone
      (P<0.001). This process was also attenuated in the D44A mutant and blocked by an
      inhibitor of the IP3R, suggesting that calcium flow through the alpha7 channel
      and activation of the Galphaq pathway are necessary for growth. Taken together,
      the findings reveal an inhibitory mechanism of alpha7 on cytoskeletal growth via
      the intracellular calcium activity of the receptor channel and the Galphaq
      signaling pathway at the growth cone.-Nordman, J. C., Kabbani, N. Microtubule
      dynamics at the growth cone are mediated by alpha7 nicotinic receptor activation
      of a Galphaq and IP3 receptor pathway. 

PMID- 24687994
TI  - A size-exclusion nanocellulose filter paper for virus removal.
AB  - This is the first time a 100% natural, unmodified nanofibrous polymer-based
      membrane is demonstrated capable of removing viruses solely based on the size
      exclusion principle, with a log10 reduction value (LRV) >= 6.3 as limited by the
      assay lower detection limit and the feed virus titre, thereby matching the
      performance of industrial synthetic polymer virus removal filters. 

PMID- 24687995
TI  - Proteomic identification of rainbow trout sperm proteins.
AB  - Proteomics represents a powerful tool for the analysis of fish spermatozoa, since
      these cells are transcriptionally inactive. The aim of the present study was to
      generate an inventory of the most prominent rainbow trout sperm proteins by SDS
      PAGE prefractionation combined with nano-LC-MS/MS based identification. This
      study provides the first in-depth analysis of the rainbow trout sperm proteome,
      with a total of 206 identified proteins. We found that rainbow trout spermatozoa
      are equipped with functionally diverse proteins related to energetic metabolism,
      signal transduction, protein turnover, transport, cytoskeleton, oxidative
      injuries, and stress and reproduction. The availability of a catalog of rainbow
      trout sperm proteins provides a crucial tool for the understanding of fundamental
      molecular processes in fish spermatozoa, for the ongoing development of novel
      markers of sperm quality and for the optimization of short- and long-term sperm
      preservation procedures. The MS data are available at ProteomeXchange with the
      dataset identifier PXD000355 and DOI 10.6019/PXD000355. 

PMID- 24687993
TI  - Fam65b is important for formation of the HDAC6-dysferlin protein complex during
      myogenic cell differentiation.
AB  - Previously, we identified family with sequence similarity 65, member B (Fam65b),
      as a protein transiently up-regulated during differentiation and fusion of human
      myogenic cells. Silencing of Fam65b expression results in severe reduction of
      myogenin expression and consequent lack of myoblast fusion. The molecular
      function of Fam65b and whether misregulation of its expression could be causative
      of muscle diseases are unknown. Protein pulldowns were used to identify Fam65b
      interacting proteins in differentiating human muscle cells and regenerating
      muscle tissue. In vitro, human muscle cells were treated with histone-deacetylase
      (HDAC) inhibitors, and expression of Fam65b and interacting proteins was studied.
      Nontreated cells were used as controls. In vivo, expression of Fam65b was down
      regulated in developing zebrafish to determine the effects on muscle development.
      Fam65b binds to HDAC6 and dysferlin, the protein mutated in limb girdle muscular
      dystrophy 2B. The tricomplex Fam65b-HDAC6-dysferlin is transient, and Fam65b
      expression is necessary for the complex to form. Treatment of myogenic cells with
      pan-HDAC or HDAC6-specific inhibitors alters Fam65b expression, while dysferlin
      expression does not change. Inhibition of Fam65b expression in developing
      zebrafish results in abnormal muscle, with low birefringence, tears at the
      myosepta, and increased embryo lethality. Fam65b is an essential component of the
      HDAC6-dysferlin complex. Down-regulation of Fam65b in developing muscle causes
      changes consistent with muscle disease.-Balasubramanian, A., Kawahara, G., Gupta,
      V. A., Rozkalne, A., Beauvais, A., Kunkel, L. M., Gussoni, E. Fam65b is important
      for formation of the HDAC6-dysferlin protein complex during myogenic cell
      differentiation. 

PMID- 24687996
TI  - Top-down tandem mass spectrometry on RNase A and B using a Qh/FT-ICR hybrid mass
      spectrometer.
AB  - Protein characterization using top-down approaches emerged with advances in high
      resolution mass spectrometers and increased diversity of available activation
      modes: collision-induced dissociation (CID), infrared multiphoton dissociation
      (IRMPD) electron capture dissociation (ECD), and electron transfer dissociation
      (ETD). Nevertheless, top-down approaches are still rarely used for glycoproteins.
      Hence, this work summarized the capacity of top-down approaches to improve
      sequence coverage and glycosylation site assignment on the glycoprotein
      Ribonuclease B (RNase B). The glycan effect on the protein fragmentation pattern
      was also investigated by comparing the fragmentation patterns of RNase B and its
      nonglycosylated analog RNase A. The experiments were performed on a Bruker 12-T
      Qh/FT-ICR SolariX mass spectrometer using vibrational (CID/IRMPD) and radical
      activation (ECD/ETD) with/without pre- or post-activation (IRMPD or CID,
      respectively). The several activation modes yielded complementary sequence
      information. The radical activation modes yielded the most extensive sequence
      coverage that was slightly improved after a CID predissociation activation event.
      The combination of the data made it possible to obtain 90% final sequence
      coverage for RNase A and 86% for RNase B. Vibrational and radical activation
      modes showed high retention of the complete glycan moiety (>98% for ETD and ECD)
      facilitating unambiguous assignment of the high-mannose glycosylation site.
      Moreover, the presence of the high-mannose glycan enhanced fragmentation around
      the glycosylation site. 

PMID- 24687997
TI  - Nanoengineered particles for enhanced intra-articular retention and delivery of
      proteins.
AB  - Localized intra-articular delivery of anti-inflammatory proteins can reduce
      inflammation in osteoarthritis but poses a challenge because of raid clearance
      within few hours of injection. A new class of polymer is developed that forms
      self-assembled nanoparticles ranging from 300 to 900 nm and demonstrates particle
      size dependent prolonged retention in intra-articular joint spaces compared to
      bolus protein over a period of 14 d. 

PMID- 24687998
TI  - Activation of central angiotensin type 2 receptors by compound 21 improves
      arterial baroreflex sensitivity in rats with heart failure.
AB  - BACKGROUND: In a previous study we demonstrated that central administration of
      compound 21 (C21), a nonpeptide AT2R agonist, inhibited sympathetic tone in
      normal rats. In this study, we hypothesized that C21 exerts a similar effect in
      rats with coronary ligation-induced heart failure (HF). METHODS: C21 was
      intracerebroventricularly infused for 7 days by osmotic mini pump. Blood pressure
      (BP) and heart rate (HR) were recorded by radiotelemetry in the conscious state
      to measure spontaneous arterial baroreflex sensitivity. Urine was collected for
      measurement of norepinephrine excretion. On the last day of C21 treatment, renal
      sympathetic nerve activity, BP, and HR were directly recorded under anesthesia,
      and the induced arterial baroreflex sensitivity was evaluated. Protein
      expressions of neuronal nitric oxide synthase (nNOS) and angiotensin II type 1
      receptor (AT1R) in the subfornical organ, paraventricular nucleus, rostral
      ventrolateral medulla, and nucleus tractus solitarius were determined by Western
      blot analysis. RESULTS: C21-treated HF rats displayed significantly less
      norepinephrine excretion (2,385.6 +/- 121.1 vs. 3,677.3 +/- 147.6 ng/24 hours; P
      < 0.05) and lower renal sympathetic nerve activity (50.2 +/- 1.9% of max vs. 70.9
      +/- 8.2% of max; P < 0.05) than vehicle-treated HF rats. C21-treated rats also
      exhibited improved spontaneous arterial baroreflex sensitivity and induced
      arterial baroreflex sensitivity. Bolus intracerebroventricular injection of
      angiotensin II-evoked pressor and sympatho-excitatory responses were attenuated
      in the C21-treated HF rats, which displayed upregulated nNOS and downregulated
      AT1R expression in the subfornical organ, paraventricular nucleus, and rostral
      ventrolateral medulla. CONCLUSIONS: Activation of central angiotensin II type 2
      receptor AT2R by C21 suppresses sympathetic outflow in rats with HF by improving
      baroreflex sensitivity and may provide important benefit in the HF syndrome.

PMID- 24688001
TI  - Full practice authority--effecting change and improving access to care: the
      Nevada journey.
AB  - PURPOSE: In 2013, Nevada shifted from a collaborative practice model to full
      practice authority. Given the challenges many states still face, this article
      provides an outline of the evolution of the "nurse practitioner" (NP) in Nevada.
      Reviewing the path Nevada took toward full practice authority, we hope to provide
      insight including lessons learned and opposition encountered to assist other
      states working toward full practice authority. DATA SOURCES: Literature searches
      were conducted on PubMed and MEDLINE. Search terms included "autonomous
      practice," "nurse practitioner," and "full practice authority." CONCLUSIONS:
      Healthcare reform will require nurse practitioners committed to legislative
      change. Nurse practitioners have the knowledge and ability to affect the
      legislative process and improve patients' access to care. With careful planning,
      full engagement, and team building, making a statute change is possible and
      should be seriously considered in states still struggling with collaborative
      relationships. IMPLICATIONS FOR PRACTICE: Nurse practitioners are well situated
      to provide primary care in the United States. Removing barriers to practice
      through statute change will empower NPs to effect positive change in our
      struggling healthcare system.

PMID- 24687999
TI  - Common variants in TGFBR2 and miR-518 genes are associated with hypertension in
      the Chinese population.
AB  - BACKGROUND: An animal study reported that TGF-beta1 maturation was linked to the
      homeostasis of blood pressure and elastogenesis of essential hypertension (EH).
      Recent advances require further research of TGF-beta1 receptor in EH. METHODS: A
      case-control study comprised of 2,012 adult hypertension case patients and 2,210
      adult control subjects was conducted, and the association with blood pressure was
      further tested in children. Logistic regression and calculated genetic risk score
      were used to evaluate the effects of one single nucleotide polymorphism (SNP) and
      multiple SNPs on EH, respectively. RESULTS: The genetic risk score of 10 SNPs
      showed a significant association with hypertension; the odds ratio of the upper
      quartile vs. the lower quartile was 1.282 (P = 4.67 * 10(-3)). rs7256241 in miR
      518 was significantly associated with diastolic blood pressure (DBP) change in
      control subjects (P = 0.002), and this association was also observed in children
      (P = 0.04). The systolic blood pressure (SBP) and DBP of female patients taking
      reserpine were higher with the C and G alleles of rs3773661 (P = 0.004) and
      rs7256241 (P = 0.002), respectively. In patients taking Zhen Ju Jiang Ya tablets,
      SBP and DBP decreased linearly with rs749794 (P = 0.004 and P = 0.048,
      respectively). SBP decreased linearly with rs1155705 (P = 0.007) and rs11709624
      (P = 0.04), but increased with rs1036096 (P = 0.03) in male patients. In male
      patients taking Jiang Ya tablets, SBP increased linearly with rs11709624 (P =
      0.007), DBP increased linearly with rs1155705 (P = 0.03) whereas decreased with
      rs7256241 (P = 0.04). CONCLUSIONS: Our results suggest that TGFBR2 and miR-518
      harbor variants that increase the risk of EH and affect blood pressure
      homeostasis as well as efficacy of antihypertensive agents.

PMID- 24688000
TI  - Common genetic variations in the vitamin D pathway in relation to blood pressure.
AB  - BACKGROUND: Vitamin D is involved in blood pressure (BP) regulation. Genetic
      variations may influence the effect of vitamin D on BP, but data from
      epidemiologic studies remain inconsistent. METHODS: We conducted a comprehensive
      genetic association study in the Women's Genome Health Study (WGHS) with genome
      wide genotype data among 23,294 women of European ancestry and in the
      International Consortium of Blood Pressure (ICBP) with genome-wide meta-analysis
      results from 69,395 men and women of European ancestry. RESULTS: First, we found
      none of 5 selected vitamin D-related candidate single nucleotide polymorphisms
      (SNPs) was associated with systolic BP (SBP) or diastolic BP (DBP). Second, in 61
      candidate SNPs involved in vitamin D metabolism and signaling, rs1507023 (in
      RBFOX1) and rs2296241 (in CYP24A1) showed significant associations with SBP, DBP,
      mean arterial pressure, or pulse pressure in the WGHS before, but not after,
      multiple testing corrections. Nominally significant associations in the ICBP were
      also not significant after corrections. Third, among 24 candidate genes across
      vitamin D pathway, associations with BP traits that meet gene-wide significance
      level were found for NCOA3 (rs2235734), RXRA (rs875444), DHCR7 (rs1790370), VDR
      (rs2544037), and NCOR2 (rs1243733, rs1147289) in the WGHS and NCOR1, TP53BP1, and
      TYRP1 in the ICBP. However, none of these associations reached significance
      threshold in both studies. CONCLUSIONS: Our study did not replicate previously
      observed associations of vitamin D-related SNPs with BP. There was suggestive
      evidence for associations in other vitamin D pathway genes; however, these
      associations either did not reach the significance threshold or were not
      replicated.

PMID- 24688002
TI  - Influence of self-management and self-management support on chronic low back pain
      patients in primary care.
AB  - PURPOSE: This study utilized a nonexperimental, cross-sectional, descriptive
      design to examine self-management (SM), self-management support (SMS), and other
      pain-related variables in chronic low back pain (CLBP), and described
      participants' perceptions of their SM, SMS, and functional ablement. DATA
      SOURCES: Data were collected from 120 participants in four primary care clinics
      using survey measures. CONCLUSIONS: SMS was found to significantly influence SM
      and mental health. Overall health significantly influenced functional ablement
      and pain intensity. Participants described using medications, exercising, and
      making lifestyle changes as most common SM strategies. Prescribing medications,
      giving encouragement, and providing information were main participant-perceived
      SMS activities. Depression and anxiety were key responses to perceptions on
      functional ablement. IMPLICATIONS FOR PRACTICE: Study findings increase our
      understanding of the SM, SMS, and functional ablement of CLBP patients with
      relevance to application in practice. There is a great need to develop evidence
      based SM and SMS programs specific to CLBP patients' needs. Nurses and nurse
      practitioners play major roles in leading this initiative. Study findings also
      reinforce the importance of psychologists and physical therapists' collaboration
      in the complex care of CLBP. Longitudinal and experimental studies are
      recommended to evaluate SM and SMS programs that include physical therapy and
      psychological care components.

PMID- 24688003
TI  - Dire prognostication with the death of the Health Accord.

PMID- 24688004
TI  - Canada Gairdner Awards honour exceptional medical research.

PMID- 24688005
TI  - Be wary of "prescribing" medical marijuana, CMA warns.

PMID- 24688007
TI  - Severe metabolic bone disease in pregnancy mimicking malignancy.

PMID- 24688008
TI  - Master of the clinical trial: 2014 Canada Gairdner Wightman Award winner Dr.
      Salim Yusuf.

PMID- 24688009
TI  - Nunavut extends implementation of suicide prevention plan.

PMID- 24688010
TI  - False hope for Canadians who study medicine abroad.

PMID- 24688012
TI  - Opal fuel reduces gas-sniffing and suicides in Australia.

PMID- 24688013
TI  - The ethics of how to manage incidental findings.

PMID- 24688014
TI  - Anxiety in middle-aged men with obstructive sleep apnea: state of the science.
AB  - PURPOSE: This article presents the state of the science of anxiety in middle-aged
      men with obstructive sleep apnea (OSA). OSA affects 10% of men in this
      population. Psychological outcomes, especially anxiety, have a significant impact
      on quality of life, yet are essentially ignored. DATA SOURCES: Search of CINAHL,
      MEDLINE, PsycINFO, and PsycARTICLES, with the key words "sleep apnea" and
      "anxiety" and with age and gender limits, resulted in 107 articles. Based on
      established inclusion criteria, 71 studies were excluded. The resulting 36
      studies were critically evaluated by sample characteristics, anxiety measurement,
      and results. CONCLUSIONS: Anxiety was noted in 34 of the 36 samples, most
      commonly measured using the Hospital Anxiety and Depression Scale, the State
      Trait Anxiety Inventory, and the Beck Anxiety Inventory. Effects of treatment on
      anxiety were significant. IMPLICATIONS FOR PRACTICE: Anxiety is common in middle
      aged men with OSA, but is not adequately studied in this population.
      Psychological screening for anxiety at the time of OSA diagnosis is warranted,
      but is not encouraged in the clinical guidelines. More primary care attention is
      needed on psychological implications that impact OSA treatment adherence.
      Advanced practice nurses can be instrumental in ensuring comprehensive assessment
      of patients with OSA, especially psychological aspects of the disease.

PMID- 24688015
TI  - Of pumps, protons, chloride gradients, and microvesicles at the immunological
      synapse.

PMID- 24688016
TI  - Fishing for holes in transporters: how protons breach the Na/K pump security
      gates.

PMID- 24688017
TI  - Novel coupling is painless.

PMID- 24688020
TI  - Genetic Evidence for Polygamy as a Mating Strategy in Caiman crocodilus.
AB  - The mating system of the spectacled caiman (Caiman crocodilus) was investigated
      in the Piagacu-Purus Sustainable Development Reserve, Amazonas, Brazil. We used 6
      polymorphic microsatellite loci to genotype 13 females and 174 hatchlings
      representing 20 nests sampled over 4 consecutive reproductive seasons (2007
      2010). Paternity was determined by 2 methods: simple counts, and statistical
      analysis using Gerud 2.0. Results were congruent between the 2 approaches, and
      the null hypothesis of single paternity was rejected in 19 of the 20 nests
      analyzed, thereby demonstrating that C. crocodilus females are polyandrous and
      that the breeding system of the species can be characterized as polygamous. The
      data suggest that 1-4 fathers were responsible for the paternity of the
      offspring, and that the males contributed differently (9-100%) to each of the 20
      nests. A total of 53 males copulated with the 20 females mothering the nests.
      This is the first study on the mating system of C. crocodilus and the frequency
      of multiple paternity is among the highest values (95%) reported thus far for
      crocodilians.

PMID- 24688018
TI  - Route, mechanism, and implications of proton import during Na+/K+ exchange by
      native Na+/K+-ATPase pumps.
AB  - A single Na(+)/K(+)-ATPase pumps three Na(+) outwards and two K(+) inwards by
      alternately exposing ion-binding sites to opposite sides of the membrane in a
      conformational sequence coupled to pump autophosphorylation from ATP and auto
      dephosphorylation. The larger flow of Na(+) than K(+) generates outward current
      across the cell membrane. Less well understood is the ability of Na(+)/K(+) pumps
      to generate an inward current of protons. Originally noted in pumps deprived of
      external K(+) and Na(+) ions, as inward current at negative membrane potentials
      that becomes amplified when external pH is lowered, this proton current is
      generally viewed as an artifact of those unnatural conditions. We demonstrate
      here that this inward current also flows at physiological K(+) and Na(+)
      concentrations. We show that protons exploit ready reversibility of
      conformational changes associated with extracellular Na(+) release from
      phosphorylated Na(+)/K(+) pumps. Reversal of a subset of these transitions allows
      an extracellular proton to bind an acidic side chain and to be subsequently
      released to the cytoplasm. This back-step of phosphorylated Na(+)/K(+) pumps that
      enables proton import is not required for completion of the 3 Na(+)/2 K(+)
      transport cycle. However, the back-step occurs readily during Na(+)/K(+)
      transport when external K(+) ion binding and occlusion are delayed, and it occurs
      more frequently when lowered extracellular pH raises the probability of
      protonation of the externally accessible carboxylate side chain. The proton route
      passes through the Na(+)-selective binding site III and is distinct from the
      principal pathway traversed by the majority of transported Na(+) and K(+) ions
      that passes through binding site II. The inferred occurrence of Na(+)/K(+)
      exchange and H(+) import during the same conformational cycle of a single
      molecule identifies the Na(+)/K(+) pump as a hybrid transporter. Whether
      Na(+)/K(+) pump-mediated proton inflow may have any physiological or
      pathophysiological significance remains to be clarified. 

PMID- 24688019
TI  - Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and alpha-conotoxin
      Vc1.1 via GABAB receptor activation.
AB  - Neuronal Cav2.1 (P/Q-type), Cav2.2 (N-type), and Cav2.3 (R-type) calcium channels
      contribute to synaptic transmission and are modulated through G protein-coupled
      receptor pathways. The analgesic alpha-conotoxin Vc1.1 acts through gamma
      aminobutyric acid type B (GABAB) receptors (GABABRs) to inhibit Cav2.2 channels.
      We investigated GABABR-mediated modulation by Vc1.1, a cyclized form of Vc1.1 (c
      Vc1.1), and the GABABR agonist baclofen of human Cav2.1 or Cav2.3 channels
      heterologously expressed in human embryonic kidney cells. 50 uM baclofen
      inhibited Cav2.1 and Cav2.3 channel Ba(2+) currents by ~40%, whereas c-Vc1.1 did
      not affect Cav2.1 but potently inhibited Cav2.3, with a half-maximal inhibitory
      concentration of ~300 pM. Depolarizing paired pulses revealed that ~75% of the
      baclofen inhibition of Cav2.1 was voltage dependent and could be relieved by
      strong depolarization. In contrast, baclofen or Vc1.1 inhibition of Cav2.3
      channels was solely mediated through voltage-independent pathways that could be
      disrupted by pertussis toxin, guanosine 5'-[beta-thio]diphosphate trilithium
      salt, or the GABABR antagonist CGP55845. Overexpression of the kinase c-Src
      significantly increased inhibition of Cav2.3 by c-Vc1.1. Conversely, coexpression
      of a catalytically inactive double mutant form of c-Src or pretreatment with a
      phosphorylated pp60c-Src peptide abolished the effect of c-Vc1.1. Site-directed
      mutational analyses of Cav2.3 demonstrated that tyrosines 1761 and 1765 within
      exon 37 are critical for inhibition of Cav2.3 by c-Vc1.1 and are involved in
      baclofen inhibition of these channels. Remarkably, point mutations introducing
      specific c-Src phosphorylation sites into human Cav2.1 channels conferred c-Vc1.1
      sensitivity. Our findings show that Vc1.1 inhibition of Cav2.3, which defines
      Cav2.3 channels as potential targets for analgesic alpha-conotoxins, is caused by
      specific c-Src phosphorylation sites in the C terminus. 

PMID- 24688021
TI  - Hypoxic stress facilitates acute activation and chronic downregulation of fanconi
      anemia proteins.
AB  - Hypoxia induces genomic instability through replication stress and dysregulation
      of vital DNA repair pathways. The Fanconi anemia (FA) proteins, FANCD2 and FANCI,
      are key members of a DNA repair pathway that responds to replicative stress,
      suggesting that they undergo regulation by hypoxic conditions. Here acute hypoxic
      stress activates the FA pathway via ubiquitination of FANCD2 and FANCI in an ATR
      dependent manner. In addition, the presence of an intact FA pathway is required
      for preventing hypoxia-induced DNA damage measurable by the comet assay, limiting
      the accumulation of gammaH2AX (a marker of DNA damage or stalled replication),
      and protecting cells from hypoxia-induced apoptosis. Furthermore, prolonged
      hypoxia induces transcriptional repression of FANCD2 in a manner analogous to the
      hypoxic downregulation of BRCA1 and RAD51. Thus, hypoxia-induced FA pathway
      activation plays a key role in maintaining genome integrity and cell survival,
      while FA protein downregulation with prolonged hypoxia contributes to genomic
      instability. IMPLICATIONS: This work highlights the critical role of the FA
      pathway in response to hypoxic stress and identifies the pathway as a therapeutic
      target under hypoxic conditions.

PMID- 24688023
TI  - CTLA-4 is expressed by activated mouse NK cells and inhibits NK Cell IFN-gamma
      production in response to mature dendritic cells.
AB  - NK cells express an array of activating and inhibitory receptors that determine
      NK cell responses upon triggering by cognate ligands. Although activating NK cell
      receptors recognize mainly ligands expressed by stressed, virus-infected, or
      transformed cells, most inhibitory receptors engage MHC class I, preventing NK
      cell activation in response to healthy cells. In this study, we provide insight
      into the regulation and function of additional receptors involved in mouse NK
      cell responses: CTLA-4 and CD28. CTLA-4 and CD28 engage the same ligands, B7-1
      and B7-2, which are primarily expressed by APCs, such as dendritic cells. Our
      data demonstrate that activation of mouse NK cells with IL-2 induces the
      expression of CTLA-4 and upregulates CD28. CTLA-4 expression in IL-2-expanded NK
      cells was further up- or downregulated by IL-12 or TGF-beta, respectively. Using
      gene-deficient NK cells, we show that CD28 induces, and CTLA-4 inhibits, IFN
      gamma release by NK cells upon engagement by the recombinant ligand, B7-1, or
      upon coculture with mature dendritic cells. Notably, we show that mouse NK cells
      infiltrating solid tumors express CD28 and CTLA-4 and respond to stimulation with
      recombinant B7-1, suggesting that the NK cell responses mediated by the CD28/CTLA
      4:B7-1/B7-2 system could be of importance during malignant disease. Accordingly,
      our study might have implications for immunotherapy of cancer based on blocking
      anti-CTLA-4 mAbs. 

PMID- 24688022
TI  - Differential ability of surface and endosomal TLRs to induce CD8 T cell responses
      in vivo.
AB  - TLR activation on dendritic cells (DCs) induces DC maturation and secretion of
      proinflammatory cytokines, both of which are important for activation and
      differentiation of CD4 T cells. The importance of TLR activation on DCs for CD8 T
      cell responses is less clear. In this study, we tested the ability of different
      TLRs to regulate CD8 T cell responses to pathogens. We found that although all
      TLRs are able to induce CD8 T cell activation in vitro, there are profound
      differences in their ability to activate CD8 T cells in vivo. The nucleic acid
      recognizing endosomal TLRs, TLR3 and TLR9, had a potent ability to induce CD8 T
      cell activation. However, the surface TLRs, TLR2 and TLR4, that recognize
      bacterial ligands were not only incapable of inducing CD8 T cell priming, but
      they had a dominant effect of inhibiting CD8 T cell expansion induced by
      activation of endosomal TLRs. We found that TLR2 and TLR4, acting in a MyD88
      dependent manner, influenced CD8 T cell priming by altering the composition of
      DCs in the draining lymph nodes. Our results have important implications for
      combined bacterial and viral infections and suggest that bacterial infections
      could constrain the ability of the host to mount effective antiviral CD8 T cell
      immunity. 

PMID- 24688025
TI  - TLR-mediated secretion of endoplasmic reticulum aminopeptidase 1 from
      macrophages.
AB  - Macrophages play an important role in host defense under several immunological,
      inflammatory, and/or infectious conditions. In our previous work, we demonstrated
      that endoplasmic reticulum aminopeptidase 1 (ERAP1) was secreted from macrophages
      in response to LPS and IFN-gamma, and it enhanced their phagocytic activity. In
      this study, we analyzed the mechanism of LPS/IFN-gamma-induced ERAP1 secretion.
      LPS/IFN-gamma-induced secretion of the enzyme from the murine macrophage cell
      line RAW264.7 was suppressed by polymyxin B. Several agonists of TLRs, such as
      Pam3CSK4, FSL-1, and ODN1826, induced its secretion. In contrast, neutralizing
      Abs to IFN-beta and TNF-alpha receptor type 1 suppressed its secretion. Using
      murine peritoneal macrophages derived from TNF-alpha and type 1 IFNR knockout
      mice, we confirmed the involvement of these two cytokines in ERAP1 secretion. In
      addition, secretion of ERAP1 from both RAW264.7 cells and murine peritoneal
      macrophages was induced by A23187 and thapsigargin and inhibited by BAPTA-AM and
      the calmodulin inhibitor W7. These results suggest that LPS/IFN-gamma-induced
      secretion of ERAP1 is mediated by TLRs via induction of intermediate cytokines
      such as IFN-beta and TNF-alpha, which in turn lead to enhanced cytosolic Ca(2+)
      levels and calmodulin activation. 

PMID- 24688024
TI  - Immunological priming requires regulatory T cells and IL-10-producing macrophages
      to accelerate resolution from severe lung inflammation.
AB  - Overwhelming lung inflammation frequently occurs following exposure to both
      direct infectious and noninfectious agents and is a leading cause of mortality
      worldwide. In that context, immunomodulatory strategies may be used to limit
      severity of impending organ damage. We sought to determine whether priming the
      lung by activating the immune system, or immunological priming, could accelerate
      resolution of severe lung inflammation. We assessed the importance of alveolar
      macrophages, regulatory T cells, and their potential interaction during
      immunological priming. We demonstrate that oropharyngeal delivery of low-dose LPS
      can immunologically prime the lung to augment alveolar macrophage production of
      IL-10 and enhance resolution of lung inflammation induced by a lethal dose of LPS
      or by Pseudomonas bacterial pneumonia. IL-10-deficient mice did not achieve
      priming and were unable to accelerate lung injury resolution. Depletion of lung
      macrophages or regulatory T cells during the priming response completely
      abrogated the positive effect of immunological priming on resolution of lung
      inflammation and significantly reduced alveolar macrophage IL-10 production.
      Finally, we demonstrated that oropharyngeal delivery of synthetic CpG
      oligonucleotides elicited minimal lung inflammation compared with low-dose LPS
      but nonetheless primed the lung to accelerate resolution of lung injury following
      subsequent lethal LPS exposure. Immunological priming is a viable
      immunomodulatory strategy used to enhance resolution in an experimental acute
      lung injury model with the potential for therapeutic benefit against a wide array
      of injurious exposures. 

PMID- 24688026
TI  - JAK2-STAT3 blockade by AG490 suppresses autoimmune arthritis in mice via
      reciprocal regulation of regulatory T Cells and Th17 cells.
AB  - IL-6-mediated STAT3 signaling is essential for Th17 differentiation and plays a
      central role in the pathogenesis of rheumatoid arthritis. To investigate the
      molecular mechanism underlying the antirheumatic effects and T cell regulatory
      effects of STAT3 inhibition, we studied the effects of the JAK 2 inhibitor AG490
      on Th17 cell/regulatory T cell (Treg) balance and osteoclastogenesis. AG490 was
      administered to mice with collagen-induced arthritis (CIA) via i.p. injection,
      and its in vivo effects were determined. Differential expression of
      proinflammatory cytokines, including IL-17A, IL-1beta, and IL-6, was analyzed by
      immunohistochemistry. Levels of phosphorylated STAT3 and STAT5 and
      differentiation of Th17 cells and Tregs after AG490 treatment in our CIA model
      were analyzed by immunostaining. In vitro development of Th17 cells and Tregs was
      analyzed by flow cytometry and real-time PCR. AG490 ameliorated the arthritic
      phenotype in CIA and increased the proportion of Foxp3(+) Tregs. In contrast, the
      proportion of IL-17A-producing T cells and levels of inflammatory markers were
      reduced in AG490-treated mice. Numbers of p-STAT3(+) CD4(+) T cells and p
      STAT5(+) CD4(+) T cells were reduced and elevated, respectively, after treatment
      with AG490. Furthermore, AG490 markedly increased the expression of molecules
      associated with Treg development (ICOS, programmed cell death protein 1, ICAM-1,
      and CD103). The development and function of osteoclasts were suppressed by AG490
      treatment. Our results suggest that AG490, specifically regulating the JAK2/STAT3
      pathway, may be a promising treatment for rheumatoid arthritis. 

PMID- 24688028
TI  - SAP facilitates recruitment and activation of LCK at NTB-A receptors during
      restimulation-induced cell death.
AB  - Upon TCR restimulation, activated, cycling T cells can undergo a self-regulatory
      form of apoptosis known as restimulation-induced cell death (RICD). We previously
      demonstrated that RICD is impaired in T cells from patients with X-linked
      lymphoproliferative disease, which lack SLAM-associated protein (SAP) expression.
      Both SAP and the specific SLAM receptor NK, T, and B cell Ag (NTB-A) are required
      for RICD, but the mechanism by which these molecules promote a strong,
      proapoptotic signal through the TCR remains unclear. In this article, we show
      that the Src-family kinase LCK, but not FYN, associates with NTB-A in activated
      human T cells. This association increased after TCR restimulation in a SAP
      dependent manner, requiring both immunoreceptor tyrosine-based switch motifs in
      the NTB-A cytoplasmic tail. Both NTB-A-associated LCK phosphorylation and kinase
      activity were enhanced in restimulated T cells, amplifying proximal TCR
      signaling. In contrast, TCR-induced LCK association with NTB-A, as well as
      phosphorylation and kinase activity, was reduced in T cells from patients with X
      linked lymphoproliferative disease or normal T cells transfected with SAP
      specific small interfering RNA, consistent with RICD resistance. Collectively,
      our data reveal how SAP nucleates a previously unknown signaling complex
      involving NTB-A and LCK to potentiate RICD of activated human T cells. 

PMID- 24688029
TI  - Legislation proposes adding pharmacist services to Medicare.

PMID- 24688027
TI  - High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase
      plasminogen activator receptor-mediated efferocytosis.
AB  - Phagocytosis of apoptotic cells (efferocytosis) is essential for regulation of
      immune responses and tissue homeostasis and is mediated by phagocytic receptors.
      In this study, we found that urokinase plasminogen activator receptor (uPAR)
      plays an important role in internalization of apoptotic cells and also
      characterized the underlying mechanisms. In a flow cytometry-based phagocytic
      assay, uPAR-deficient macrophages displayed significant defect in internalization
      but not tethering of apoptotic cells. When uPAR-deficient mice were challenged
      with apoptotic cells, they exhibited pronounced splenomegaly resulting from
      accumulation of abundant apoptotic cells in spleen. Overexpression of uPAR in HEK
      293 cells enhanced efferocytosis, which was inhibited by Annexin V and
      phosphatidylserine (PS) liposome, suggesting that uPAR-mediated efferocytosis is
      dependent on PS. In serum lacking high m.w. kininogen (HK), a uPAR ligand, uPAR
      mediated efferocytosis was significantly attenuated, which was rescued by
      replenishment of HK. As detected by flow cytometry, HK selectively bound to
      apoptotic cells, but not viable cells. In purified systems, HK was specifically
      associated with PS liposome. HK binding to apoptotic cells induced its rapid
      cleavage to the two-chain form of HK (HKa) and bradykinin. Both the H chain and L
      chain of HKa were associated with PS liposome and apoptotic cells. HKa has higher
      binding affinity than HK to uPAR. Overexpression of Rac1/N17 cDNA inhibited uPAR
      mediated efferocytosis. HK plus PS liposome stimulated a complex formation of
      CrkII with p130Cas and Dock-180 and Rac1 activation in uPAR-293 cells, but not in
      control HEK-293 cells. Thus, uPAR mediates efferocytosis through HK interaction
      with PS on apoptotic cells and activation of the Rac1 pathway. 

PMID- 24688030
TI  - Managing missed doses could improve VTE prevention.

PMID- 24688031
TI  - Contract pharmacies come under 340B scrutiny.

PMID- 24688033
TI  - Advancing the pharmacy practice model through statewide resident collaboration.

PMID- 24688034
TI  - Analysis of pharmacists' use of Twitter.

PMID- 24688035
TI  - Tedizolid: a new oxazolidinone antimicrobial.
AB  - PURPOSE: The mechanism of action, pharmacokinetics, pharmacodynamics, and
      clinical efficacy and safety of an investigational second-generation
      oxazolidinone are reviewed. SUMMARY: Tedizolid is a protein synthesis inhibitor
      in clinical development for the treatment of gram-positive infections. Similar to
      linezolid, tedizolid works by binding to the 23S ribosomal RNA of the 50S
      subunit, thereby preventing the formation of the 70S initiation complex and
      inhibiting protein synthesis. Tedizolid has demonstrated potent in vitro activity
      against multidrug-resistant gram-positive bacteria such as methicillin-resistant
      Staphylococcus aureus (MRSA), Streptococcus pneumoniae, and vancomycin-resistant
      enterococci (VRE), including some linezolid-resistant strains. Tedizolid has a
      favorable pharmacokinetic profile that allows for once-daily dosing and easy i.v.
      to-oral conversion. Unlike linezolid, tedizolid has not been shown to interact
      with serotonergic agents in clinical studies. Two Phase III studies in patients
      with acute bacterial skin and skin structure infections have demonstrated the
      noninferiority of 6 days of tedizolid therapy (200 mg i.v. or orally once daily)
      relative to 10 days of linezolid therapy. In clinical trials to date, overall
      rates of treatment-related adverse effects with linezolid and tedizolid were
      comparable (40.8% versus 43.3%), with nausea being the most commonly reported
      adverse effect associated with tedizolid use (16% of patients). Planned studies
      will investigate tedizolid's potential role in the treatment of community
      acquired bacterial pneumonia, hospital-acquired/ventilator-associated bacterial
      pneumonia, and bacteremia. CONCLUSION: Tedizolid is an investigational
      oxazolidinone antibiotic for the treatment of multidrug-resistant gram-positive
      pathogens such as MRSA, Streptococcus pneumoniae, and VRE, including some
      linezolid-resistant strains.

PMID- 24688036
TI  - High-dose transdermal nicotine replacement for tobacco cessation.
AB  - PURPOSE: The safety and efficacy of high-dose transdermal nicotine-replacement
      therapy (NRT) for the treatment of tobacco-use cessation were reviewed. SUMMARY:
      Transdermal nicotine doses of 7, 14, and 21 mg daily are approved by the Food and
      Drug Administration for use in tobacco cessation. However, studies have suggested
      that these doses are more adequate for people who smoke fewer than 20 cigarettes
      per day. A literature search was conducted to identify English-language studies
      that evaluated the use of transdermal nicotine doses of >=42 mg daily. A total of
      11 articles were identified, representing 10 separate trials. In terms of safety,
      the majority of the trials had no reports of serious adverse events related to
      transdermal NRT at doses of >=42 mg daily. A dose-response relationship with
      adverse events occurred in most trials. In terms of efficacy, a numerically
      higher abstinence rate was achieved with high-dose transdermal NRT in all trials
      but 1. However, none of the studies showed significant differences in final
      abstinence rates at follow-up. Some reasons why statistical significance was not
      achieved in these trials may be related to the limitations of these trials, such
      as their small samples and the lack of a power calculation. A more robust trial
      is needed to support higher nicotine transdermal doses in tobacco cessation and
      to help elucidate which patient population would be most suitable for their use.
      CONCLUSION: The safety and efficacy of high-dose transdermal NRT for tobacco
      cessation have not been established in the medical literature.

PMID- 24688037
TI  - Prolonged coagulopathy after brodifacoum exposure.
AB  - PURPOSE: A case of brodifacoum exposure leading to coagulopathy lasting for
      approximately one year despite treatment with large doses of phytonadione is
      reported. SUMMARY: A 36-year-old man was diagnosed with severe coagulopathy. He
      was treated and discharged on 40 mg of oral phytonadione daily. The cause of the
      coagulopathy remained unknown at discharge, but the hematologist theorized that
      exposure to a vitamin K antagonist was likely the source of the patient's
      condition. The patient was rehospitalized one week later with an International
      Normalized Ratio (INR) of 5.9 despite self-reported medication compliance. Oral
      phytonadione was increased to 80 mg daily. The patient was seen at an outpatient
      hematology clinic for several months and continued on tapering dosages of oral
      phytonadione. A coagulopathy panel from the original hospitalization confirmed
      the presence of brodifacoum, though the method of exposure remained unclear. He
      was lost to follow-up until approximately nine months later, when he reported
      taking 10 mg daily of oral phytonadione and had an INR of 1. Oral phytonadione
      was discontinued. Two months later, his INR was greater than 9, despite an
      undetectable level of brodifacoum. He was rehospitalized with oropharyngeal
      hematoma approximately 1 year after the initial coagulopathy diagnosis. The
      patient was discharged on 40 mg oral phytonadione daily with outpatient follow
      up. CONCLUSION: A patient with brodifacoum exposure ingested brodifacoum had
      coagulopathy that lasted approximately one year despite long-term treatment with
      large dosages of oral phytonadione. The coagulopathy persisted even when
      brodifacoum was undetectable in the serum. Long-term treatment with high-dose
      phytonadione is expensive, which may influence medication compliance.

PMID- 24688038
TI  - Probable drug-induced liver injury associated with aliskiren: case report and
      review of adverse event reports from pharmacovigilance databases.
AB  - PURPOSE: A case of probable drug-induced liver injury (DILI) attributed to use of
      the antihypertensive agent aliskiren is reported. SUMMARY: A 61-year-old woman
      undergoing routine liver function monitoring in conjunction with long-term
      antiepileptic therapy was noted to have an asymptomatic acute hepatic cytolysis 1
      month after the initiation of concomitant aliskiren therapy (150 mg/day). Liver
      enzyme testing showed dramatically elevated aspartate transaminase (AST) and
      alanine transaminase (ALT) concentrations, with substantial rises also noted in
      gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) levels. The
      calculated ALT:ALP value indicated hepatocellular injury. On discontinuation of
      aliskiren use, rapid biological improvement occurred, including normalization of
      serum AST and a sharp decline in serum ALT within one week and the return of GGT
      and ALP levels to baseline a few weeks later; the patient's AST and ALT
      concentrations remained normal during 18 months of subsequent monitoring. Using
      the algorithm of Naranjo et al. and a DILI-specific causality assessment
      instrument, it was determined that aliskiren use was the probable cause of the
      patient's liver injury. While this is believed to be the first report of
      aliskiren-associated DILI in the professional literature, a review of information
      from several European and North American pharmacovigilance databases (through
      October 2012) identified 117 reports of suspected aliskiren hepatotoxicity,
      including 6 reports of liver failure and 12 reports of deaths. CONCLUSION:
      Asymptomatic acute hepatic cytolysis was observed in a 61-year-old woman
      approximately one month after initiation of aliskerin for treatment of
      hypertension. Improvement in AST and ALT concentrations was observed shortly
      after the drug was discontinued.

PMID- 24688039
TI  - Variations in pharmacy-based transition-of-care activities in the United States:
      a national survey.
AB  - PURPOSE: A national survey was conducted to assess pharmacist roles in transition
      of-care (TOC) activities in the United States. METHODS: An online survey was sent
      to 1246 pharmacy directors who were members of the American Society of Health
      System Pharmacists to assess their involvement in TOC activities including
      medication reconciliation, admission histories, medication counseling, and
      postdischarge follow-up; pharmacy student and pharmacy technician involvement in
      TOC activities; the use of technology to facilitate TOC activities; and barriers
      to performing such activities. RESULTS: A total of 393 respondents completed the
      survey (31.5% response rate). Twenty-seven percent of respondents indicated that
      pharmacists complete medication histories on admission, and 5% indicated that
      pharmacy technicians complete medication histories. Most respondents indicated
      that pharmacists do not routinely or consistently provide patients with tools to
      facilitate medication adherence before hospital discharge and that pharmacists do
      not routinely or consistently follow up with patients after discharge. Fifty-six
      percent of respondents indicated that pharmacists provide patient education for
      specific medications or for medications for specific diseases. Few respondents
      indicated that student pharmacists are involved with TOC activities. Most
      respondents either agreed or strongly agreed that it is important for pharmacists
      to be involved in TOC activities for hospitalized patients. CONCLUSION:
      Approximately one third of survey respondents indicated that pharmacists complete
      medication histories. Most respondents indicated that pharmacists do not
      routinely or consistently provide patients with tools to facilitate medication
      adherence before hospital discharge or follow up with patients after discharge.
      Lack of pharmacy staff resources and insufficient recognition of the value of
      pharmacists' provision of TOC by health care executives, medical staff, nursing
      staff, and other health care professionals were the most frequently cited
      barriers to pharmacists assuming more significant roles in the TOC at the
      respondent's institution.

PMID- 24688041
TI  - John W. Webb Lecture. The essence of leadership.

PMID- 24688040
TI  - Stability of clonidine suspension in oral plastic syringes.
AB  - PURPOSE: The stability of clonidine suspensions stored at room temperature and
      under refrigeration for three months was evaluated. METHODS: Oral suspensions of
      clonidine 0.01 mg/mL were prepared in Ora-Blend and stored in clear plastic
      syringes at 25  degrees C and 4  degrees C. Samples were collected from each
      syringe at the time of preparation, at weekly intervals for up to 28 days, and on
      days 42, 56, 77, and 91. Changes in color, taste, and pH, as well as visual
      evidence of precipitation, were used to determine physical compatibility.
      Immediately after the physical observations were made, 1.5-mL samples from each
      syringe were transferred to polypropylene freezer vials and stored at -85 
      degrees C until high-performance liquid chromatographic (HPLC) analysis. The
      samples were analyzed by a validated stability-indicating HPLC-ultraviolet-light
      detection method. Stability was defined as the retention of at least 90% of the
      initial clonidine concentration. The precision of the assay was evaluated by
      intraday and interday validation methods. RESULTS: Clonidine suspensions stored
      at 25  degrees C and 4  degrees C maintained 99.2% and 99.0% of the initial
      concentration for 91 days, respectively. No interfering peaks were generated by
      forced degradation of clonidine with heat, hydrochloric acid, sodium hydroxide,
      or hydrogen peroxide There were no notable changes in pH, and all samples
      remained physically unchanged during the study period. CONCLUSION: An
      extemporaneously prepared suspension of clonidine 0.01 mg/mL in Ora-Blend was
      stable for at least 91 days when stored in clear plastic syringes at either 25 
      degrees C or 4  degrees C.

PMID- 24688042
TI  - Stability of penicillin G sodium diluted with 0.9% sodium chloride injection or
      5% dextrose injection and stored in polyvinyl chloride bag containers and
      elastomeric pump containers.
AB  - PURPOSE: The stability of penicillin G sodium solutions stored in polyvinyl
      chloride (PVC) bags or elastomeric pump containers was studied. METHODS: Test
      samples were prepared by diluting powdered penicillin G sodium (10 million
      units/10-mL vial) to solutions of 2,500 or 50,000 units/mL with 0.9% sodium
      chloride injection or 5% dextrose injection. The preparations were transferred to
      250-mL PVC bags and elastomeric pump containers. All samples were prepared in
      triplicate and stored at 5 degrees C. Chemical stability was measured by a
      stability-indicating high-performance liquid chromatographic (HPLC) assay and by
      pH evaluation. Particulate matter was evaluated according to compendial standards
      using a light-obscuration particle count test. Preparations were visually
      examined throughout the study. RESULTS: After 21 days of storage, all test
      samples remained chemically stable, with an HPLC assay recovery value of more
      than 90% of the initial value. After 28 days, all samples prepared with either
      diluent and stored in PVC bags, as well as the samples diluted to 2,500 units/mL
      with sodium chloride injection and stored in elastomeric pump containers, did not
      meet the recovery acceptance limit. For all test samples, the mean pH
      consistently decreased during storage, from about 6.4 to about 5.5. Particle
      counts remained acceptable throughout the study, and no change in appearance was
      observed. CONCLUSION: Penicillin G for injection (2,500 and 50,000 units/mL)
      diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored at
      5 degrees C in PVC containers or elastomeric pump containers was physically and
      chemically stable for a period of at least 21 days.

PMID- 24688043
TI  - Automation and improved technology to promote database synchronization.

PMID- 24688046
TI  - Inhibition of mTOR signaling reduces PELP1-mediated tumor growth and therapy
      resistance.
AB  - Proline, Glutamic acid-, and Leucine-rich Protein 1 (PELP1) is a proto-oncogene
      that modulates estrogen receptor (ER) signaling. PELP1 expression is upregulated
      in breast cancer, contributes to therapy resistance, and is a prognostic marker
      of poor survival. In a subset of breast tumors, PELP1 is predominantly localized
      in the cytoplasm and PELP1 participates in extranuclear signaling by facilitating
      ER interactions with Src and phosphoinositide 3-kinase (PI3K). However, the
      mechanism by which PELP1 extranuclear actions contributes to cancer progression
      and therapy resistance remains unclear. In this study, we discovered that PELP1
      cross-talked with the serine/threonine protein kinase mTOR and modulated mTOR
      signaling. PELP1 knockdown significantly reduced the activation of mTOR
      downstream signaling components. Conversely, PELP1 overexpression excessively
      activated mTOR signaling components. We detected the presence of the mTOR
      signaling complex proteins in PELP1 immunoprecipitates. mTOR-targeting drugs
      (rapamycin and AZD8055) significantly reduced proliferation of PELP1
      overexpressed breast cancer cells in both in vitro and in vivo xenograft tumor
      models. MCF7 cells that uniquely retain PELP1 in the cytoplasm showed resistance
      to hormonal therapy and mTOR inhibitors sensitized PELP1cyto cells to hormonal
      therapy in xenograft assays. Notably, immunohistochemical studies using xenograft
      tumors derived from PELP1 overexpression model cells showed increased mTOR
      signaling and inhibition of mTOR rendered PELP1-driven tumors to be highly
      sensitive to therapeutic inhibition. Collectively, our data identified the PELP1
      mTOR axis as a novel component of PELP1 oncogenic functions and suggest that mTOR
      inhibitor(s) will be effective chemotherapeutic agents for downregulating PELP1
      oncogenic functions.

PMID- 24688047
TI  - Differential antitumor activity of aflibercept and bevacizumab in patient-derived
      xenograft models of colorectal cancer.
AB  - The recombinant fusion protein aflibercept (ziv-aflibercept in the United States)
      binds VEGF-A, VEGF-B, and placental growth factor (PlGF). The monoclonal antibody
      bevacizumab binds VEGF-A. Recent studies hypothesized that dual targeting of
      VEGF/PlGF is more beneficial than targeting either ligand. We compared activity
      of aflibercept versus bevacizumab in 48 patient-derived xenograft (PDX)
      colorectal cancer models. Nude mice engrafted subcutaneously with PDX colorectal
      cancer tumors received biweekly aflibercept, bevacizumab, or vehicle injections.
      Differential activity between aflibercept and bevacizumab, determined by mouse
      (m), human (h), VEGF-A, and PlGF levels in untreated tumors, was measured.
      Aflibercept induced complete tumor stasis in 31 of 48 models and bevacizumab in 2
      of 48. Based on statistical analysis, aflibercept was more active than
      bevacizumab in 39 of 48 models; in 9 of 39 of these models, bevacizumab was
      considered inactive. In 9 of 48 remaining models, aflibercept and bevacizumab had
      similar activity. Tumor levels of hVEGF-A (range 776-56,039 pg/mg total protein)
      were ~16- to 1,777-fold greater than mVEGF-A (range 8-159 pg/mg total protein).
      Tumor levels of mPlGF (range 104-1,837 pg/mg total protein) were higher than
      hPlGF (range 0-543 pg/mg total protein) in 47 of 48 models. Tumor cells were the
      major source of VEGF; PlGF was primarily produced by tumor stroma. Because tumor
      levels of hVEGF-A were far greater than mVEGF-A, bevacizumab's inability to bind
      mVEGF-A is unlikely to explain higher and more consistent aflibercept activity.
      Neutralizing PlGF and VEGFR-1 activation may be a factor and should be
      investigated in future studies. In these colorectal cancer PDX models,
      aflibercept demonstrated greater antitumor activity than bevacizumab.

PMID- 24688048
TI  - A novel CDK9 inhibitor shows potent antitumor efficacy in preclinical hematologic
      tumor models.
AB  - DNA-dependent RNA polymerase II (RNAP II) largest subunit RPB1 C-terminal domain
      (CTD) kinases, including CDK9, are serine/threonine kinases known to regulate
      transcriptional initiation and elongation by phosphorylating Ser 2, 5, and 7
      residues on CTD. Given the reported dysregulation of these kinases in some
      cancers, we asked whether inhibiting CDK9 may induce stress response and
      preferentially kill tumor cells. Herein, we describe a potent CDK9 inhibitor,
      LY2857785, that significantly reduces RNAP II CTD phosphorylation and
      dramatically decreases MCL1 protein levels to result in apoptosis in a variety of
      leukemia and solid tumor cell lines. This molecule inhibits the growth of a broad
      panel of cancer cell lines, and is particularly efficacious in leukemia cells,
      including orthotopic leukemia preclinical models as well as in ex vivo acute
      myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. Thus,
      inhibition of CDK9 may represent an interesting approach as a cancer therapeutic
      target, especially in hematologic malignancies.

PMID- 24688049
TI  - MCL-1 degradation mediated by JNK activation via MEKK1/TAK1-MKK4 contributes to
      anticancer activity of new tubulin inhibitor MT189.
AB  - Colchicine site-targeted tubulin inhibitors are a promising type of anticancer
      drugs. MT189 is a new derivative of MT119, a previously reported colchicine site
      binding antitubulin agent. In this study, MT189 was demonstrated to retain the
      property of MT119 in disrupting microtubulin via binding to the colchicine site,
      causing mitotic arrest and inducing apoptosis, and to display 8.7-fold enhanced
      proliferative inhibition in a panel of cancer cells. MT189 was shown to elicit in
      vivo anticancer effects on MDA-MB-231 xenografts in nude mice, and the tumor
      growth was suppressed by 35.9% over 14 days. MT189 led to degradation of MCL-1, a
      member of the antiapoptotic BCL-2 protein family. Its overexpression reduced but
      its silenced expression increased the apoptotic induction followed by the
      treatment with MT189. Moreover, the treatment with MT189 caused activation of the
      MEKK1/TAK1-MKK4-JNK signaling pathway. The activated JNK resulted in
      phosphorylation of MCL-1, which facilitated its ubiquitination-mediated
      degradation. Our results show that MT189 inhibits microtubulin polymerization by
      binding to the colchicine site. Relief of apoptotic suppression by MCL-1
      degradation together with mitotic arrest contributes to the anticancer activity
      of MT189.

PMID- 24688050
TI  - Targeting multiple key signaling pathways in melanoma using leelamine.
AB  - Melanoma is a highly drug-resistant cancer with resistance developing to agents
      targeting single proteins. To circumvent this problem, a new class of agent
      inhibiting multiple key pathways important in this disease is being developed to
      reduce the likelihood of developing resistant disease. The phosphoinositide 3
      kinase (PI3K), mitogen-activated protein kinase (MAPK), and STAT3 pathways are
      constitutively activated in 50% to 70% of melanomas, promoting disease
      development. To identify a drug simultaneously targeting the PI3K, MAPK, and
      STAT3 cascades, a natural product library was screened to identify leelamine as a
      potential inhibitor. Leelamine was 4.5-fold more effective at inhibiting cultured
      melanoma cell survival than normal cells, with average IC(50) values of 2 and 9.3
      MUmol/L, respectively. It inhibited cellular proliferation at a concentration of
      2.5 MUmol/L by 40% to 80% and longer exposure increased apoptosis 600%. Leelamine
      inhibited the growth of preexisting xenografted melanoma tumors by an average of
      60% by targeting the PI3K, MAPK, and STAT3 pathways without affecting animal body
      weight or blood markers of major organ function. The mechanism of action of
      leelamine is mediated by disruption of cholesterol transport, causing decreased
      cellular proliferation and consequently leading to increased tumor cell apoptosis
      as well as decreased tumor vascularization. Thus, a unique agent and novel
      mechanism of action has been identified for the treatment of melanoma that acts
      by inhibiting the activity of three major signaling pathways regulating the
      development of this disease.

PMID- 24688051
TI  - Leelamine mediates cancer cell death through inhibition of intracellular
      cholesterol transport.
AB  - Leelamine is a promising compound for the treatment of cancer; however, the
      molecular mechanisms leading to leelamine-mediated cell death have not been
      identified. This report shows that leelamine is a weakly basic amine with
      lysosomotropic properties, leading to its accumulation inside acidic organelles
      such as lysosomes. This accumulation leads to homeostatic imbalance in the
      lysosomal endosomal cell compartments that disrupts autophagic flux and
      intracellular cholesterol trafficking as well as receptor-mediated endocytosis.
      Electron micrographs of leelamine-treated cancer cells displayed accumulation of
      autophagosomes, membrane whorls, and lipofuscin-like structures, indicating
      disruption of lysosomal cell compartments. Early in the process, leelamine
      mediated killing was a caspase-independent event triggered by cholesterol
      accumulation, as depletion of cholesterol using beta-cyclodextrin treatment
      attenuated the cell death and restored the subcellular structures identified by
      electron microscopy. Protein microarray-based analyses of the intracellular
      signaling cascades showed alterations in RTK-AKT/STAT/MAPK signaling cascades,
      which was subsequently confirmed by Western blotting. Inhibition of Akt, Erk, and
      Stat signaling, together with abnormal deregulation of receptor tyrosine kinases,
      was caused by the inhibition of receptor-mediated endocytosis. This study is the
      first report demonstrating that leelamine is a lysosomotropic, intracellular
      cholesterol transport inhibitor with potential chemotherapeutic properties
      leading to inhibition of autophagic flux and induction of cholesterol
      accumulation in lysosomal/endosomal cell compartments. Importantly, the findings
      of this study show the potential of leelamine to disrupt cholesterol homeostasis
      for treatment of advanced-stage cancers.

PMID- 24688052
TI  - KRAS mutation status is associated with enhanced dependency on folate metabolism
      pathways in non-small cell lung cancer cells.
AB  - KRAS gene mutation is linked to poor prognosis and resistance to therapeutics in
      non-small cell lung cancer (NSCLC). In this study, we have explored the
      possibility of exploiting inherent differences in KRAS-mutant cell metabolism for
      treatment. This study identified a greater dependency on folate metabolism
      pathways in KRAS mutant compared with KRAS wild-type NSCLC cell lines. Microarray
      gene expression and biologic pathway analysis identified higher expression of
      folate metabolism- and purine synthesis-related pathways in KRAS-mutant NSCLC
      cells compared with wild-type counterparts. Moreover, pathway analysis and
      knockdown studies suggest a role for MYC transcriptional activity in the
      expression of these pathways in KRAS-mutant NSCLC cells. Furthermore, KRAS
      knockdown and overexpression studies demonstrated the ability of KRAS to regulate
      expression of genes that comprise folate metabolism pathways. Proliferation
      studies demonstrated higher responsiveness to methotrexate, pemetrexed, and other
      antifolates in KRAS-mutant NSCLC cells. Surprisingly, KRAS gene expression is
      downregulated in KRAS wild-type and KRAS-mutant cells by antifolates, which may
      also contribute to higher efficacy of antifolates in KRAS-mutant NSCLC cells. In
      vivo analysis of multiple tumorgraft models in nude mice identified a KRAS-mutant
      tumor among the pemetrexed-responsive tumors and also demonstrated an association
      between expression of the folate pathway gene, methylenetetrahydrofolate
      dehydrogenase 2 (MTHFD2), and antifolate activity. Collectively, we identify
      altered regulation of folate metabolism in KRAS-mutant NSCLC cells that may
      account for higher antifolate activity in this subtype of NSCLC.

PMID- 24688053
TI  - Natural compound Alternol induces oxidative stress-dependent apoptotic cell death
      preferentially in prostate cancer cells.
AB  - Prostate cancers at the late stage of castration resistance are not responding
      well to most of current therapies available in clinic, reflecting a desperate
      need of novel treatment for this life-threatening disease. In this study, we
      evaluated the anticancer effect of a recently isolated natural compound,
      Alternol, in multiple prostate cancer cell lines with the properties of advanced
      prostate cancers in comparison to prostate-derived nonmalignant cells. As
      assessed by trypan blue exclusion assay, significant cell death was observed in
      all prostate cancer cell lines except DU145 but not in nonmalignant (RWPE-1 and
      BPH1) cells. Further analyses revealed that Alternol-induced cell death was an
      apoptotic response in a dose- and time-dependent manner, as evidenced by the
      appearance of apoptosis hallmarks such as caspase-3 processing and PARP cleavage.
      Interestingly, Alternol-induced cell death was completely abolished by reactive
      oxygen species scavengers N-acetylcysteine and dihydrolipoic acid. We also
      demonstrated that the proapoptotic Bax protein was activated after Alternol
      treatment and was critical for Alternol-induced apoptosis. Animal xenograft
      experiments in nude mice showed that Alternol treatment largely suppressed tumor
      growth of PC-3 xenografts but not Bax-null DU-145 xenografts in vivo. These data
      suggest that Alternol might serve as a novel anticancer agent for patients with
      late-stage prostate cancer.

PMID- 24688055
TI  - Floral colleters in Pleurothallidinae (Epidendroideae: Orchidaceae).
AB  - PREMISE OF THE STUDY: The term colleter is applied to trichomes or emergences
      positioned close to developing vegetative and floral meristems that secrete a
      sticky, mucilaginous, and/or lipophilic exudate. Several ecological functions are
      attributed to these glands, but none are exclusive to colleters. Patterns of
      morphology and distribution of colleters may be valuable for systematics and
      phylogeny, especially concerning problematic and large groups such as the
      subtribe Pleurothallidinae, and are also essential to understand the evolution of
      these glands in Orchidaceae as a whole. METHODS: We used scanning electron and
      light microscopy to examine the structure and occurrence of trichomes on bracts
      and sepals and in the invaginations of the external ovary wall (IEOW) in flowers
      in several developmental stages from species in seven genera. KEY RESULTS: The
      exudate was composed of polysaccharides, lipophilic, and phenolic compounds.
      Colleters were secretory only during the development of floral organs, except for
      the glands in the IEOW that were also active in flowers at anthesis. After the
      secretory phase, fungal hyphae were found penetrating senescent trichomes.
      CONCLUSIONS: Trichome-like colleters seem to be a widespread character in
      Epidendroideae, and digitiform colleters are possibly the common type in this
      subfamily. Mucilage from IEOW colleters may aid in the establishment of symbiotic
      fungi necessary for seed germination. The presence of colleters in the IEOW may
      be a case of homeoheterotopy, in which extrafloral nectaries that produce simple
      sugar-based secretions (as in other orchid species) have changed to glands that
      produce secretions with complex polysaccharides, as in Pleurothallidinae.

PMID- 24688054
TI  - Muscarinic receptor activation increases hERG channel expression through
      phosphorylation of ubiquitin ligase Nedd4-2.
AB  - The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of
      the rapidly activating delayed rectifier potassium channel, which is important
      for cardiac repolarization. Reduction of hERG current due to genetic mutations or
      drug interferences causes long QT syndrome, leading to cardiac arrhythmias and
      sudden death. To date, there is no effective therapeutic method to restore or
      enhance hERG channel function. Using cell biology and electrophysiological
      methods, we found that the muscarinic receptor agonist carbachol increased the
      expression and function of hERG, but not ether-a-go-go or Kv1.5 channels stably
      expressed in human embryonic kidney cells. The carbachol-mediated increase in
      hERG expression was abolished by the selective M3 antagonist 4-DAMP (1,1-dimethyl
      4-diphenylacetoxypiperidinium iodide) but not by the M2 antagonist AF-DX 116
      (11[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6H-pyrido[2,3
      b] [1,4]benzodiazepine-6-one). Treatment of cells with carbachol reduced the hERG
      ubiquitin interaction and slowed the rate of hERG degradation. We previously
      showed that the E3 ubiquitin ligase Nedd4-2 mediates degradation of hERG
      channels. Here, we found that disrupting the Nedd4-2 binding domain in hERG
      completely eliminated the effect of carbachol on hERG channels. Carbachol
      treatment enhanced the phosphorylation level, but not the total level, of Nedd4
      2. Blockade of the protein kinase C (PKC) pathway abolished the carbachol-induced
      enhancement of hERG channels. Our data suggest that muscarinic activation
      increases hERG channel expression by phosphorylating Nedd4-2 via the PKC pathway.

PMID- 24688056
TI  - Key plants preserve elements of culture: a study over distance and time of fresh
      crops in Puerto Rican markets in Hartford, Connecticut, "A moveable feast".
AB  - PREMISE OF THE STUDY: People retain culinary customs when they migrate. We tested
      this commitment via the study of Puerto Rican fresh produce markets in the
      continental United States over time, 18 yr, and space, by comparisons with source
      markets in Puerto Rico (PR). METHODS: A survey of Puerto Rican markets in
      Hartford (HT), Connecticut in 1993-1994 was repeated in 2009-2010. A comparative
      study was made at open-air markets in PR in 2009. Surveys recorded fresh crops,
      and interviews with vendors and Hartford Puerto Rican residents provided context.
      KEY RESULTS: We recorded 84 plant crops (64 species; 32 families) for seven
      categories. The largest category was viandas (fresh, starchy "root" crops and
      immature fruits), followed by saborizantes (flavorings). In the second HT survey,
      80% of the crops were still present. And ~90% of the HT 1993-1994 crops and ~75%
      of the HT 2009-2010 crops were shared with markets in PR. CONCLUSIONS: On the
      basis of our results, we suggest two new concepts. The persistence of these
      largely tropical foods in a temperate market far removed from tropical PR shows
      the importance of basic foods as an element of cultural identification. We
      recognize this stability as an example of "culinary cultural conservation".
      Second, analysis of these fresh produce markets leads to the conclusion that
      viandas are the most prominent in diversity, persistence over time and distance,
      volume, and in terms of consumers' "willingness to pay". Accordingly, we consider
      the viandas a good example of a "cultural keystone food group", a food group that
      is emblematic of a community's culinary conservation.

PMID- 24688057
TI  - A plastid DNA phylogeny of tribe Miliuseae: insights into relationships and
      character evolution in one of the most recalcitrant major clades of Annonaceae.
AB  - PREMISE OF THE STUDY: Tribe Miliuseae (~25 genera and ~510 species) includes a
      substantial part of the species and generic diversity in the pantropical
      flowering-plant family Annonaceae (~108 genera and ~2400 species). Previous
      molecular phylogenetic analyses have failed to resolve the backbone phylogeny of
      the tribe, impeding biogeographical and evolutionary studies. We use a dense
      generic taxon sample (~89% of generic diversity in Miliuseae) and plastid DNA
      sequence data (~7 kb) to clarify the phylogenetic relationships of and within the
      tribe. METHODS: Parsimony and Bayesian phylogenetic reconstructions and ancestral
      character-state reconstructions of several reproductive characters were
      performed. KEY RESULTS: Dendrokingstoniae, Monocarpieae, and Miliuseae are
      recovered in a strongly supported clade, and each tribe is strongly supported as
      monophyletic. Miliuseae are characterized by a synapomorphic
      cryptoaperturate/disulculate pollen apertural system. Stenanona is shown to be
      nested within the paraphyletic genus Desmopsis. The only Neotropical clade
      (Sapranthus, Tridimeris, Desmopsis, and Stenanona) in the predominantly Asian
      Miliuseae is shown to be closely related to an undescribed genus from continental
      Southeast Asia and the Indo-Malayan and Austral-Pacific genus Meiogyne. Ancestral
      character-state reconstructions of several reproductive characters that are
      diagnostically important at the generic level indicate a considerable degree of
      homoplasy. CONCLUSIONS: The results improve our understanding of the
      relationships of and within Miliuseae, but parts of the backbone of the phylogeny
      remain poorly supported. Additional data from variable nuclear markers or reduced
      genome-representation approaches seem to be required to further resolve
      relationships within this recalcitrant clade.

PMID- 24688058
TI  - Phylogeny, character evolution, and biogeography of Cuscuta (dodders;
      Convolvulaceae) inferred from coding plastid and nuclear sequences.
AB  - PREMISE OF THE STUDY: The parasitic genus Cuscuta, containing some 200 species
      circumscribed traditionally in three subgenera, is nearly cosmopolitan, occurring
      in a wide range of habitats and hosts. Previous molecular studies, on subgenera
      Grammica and Cuscuta, delimited major clades within these groups. However, the
      sequences used were unalignable among subgenera, preventing the phylogenetic
      comparison across the genus. METHODS: We conducted a broad phylogenetic study
      using rbcL and nrLSU sequences covering the morphological, physiological, and
      geographical diversity of Cuscuta. We used parsimony methods to reconstruct
      ancestral states for taxonomically important characters. Biogeographical
      inferences were obtained using statistical and Bayesian approaches. KEY RESULTS:
      Four well-supported major clades are resolved. Two of them correspond to
      subgenera Monogynella and Grammica. Subgenus Cuscuta is paraphyletic, with
      section Pachystigma sister to subgenus Grammica. Previously described cases of
      strongly supported discordance between plastid and nuclear phylogenies,
      interpreted as reticulation events, are confirmed here and three new cases are
      detected. Dehiscent fruits and globose stigmas are inferred as ancestral
      character states, whereas the ancestral style number is ambiguous.
      Biogeographical reconstructions suggest an Old World origin for the genus and
      subsequent spread to the Americas as a consequence of one long-distance
      dispersal. CONCLUSIONS: Hybridization may play an important yet underestimated
      role in the evolution of Cuscuta. Our results disagree with scenarios of
      evolution (polarity) previously proposed for several taxonomically important
      morphological characters, and with their usage and significance. While several
      cases of long-distance dispersal are inferred, vicariance or dispersal to
      adjacent areas emerges as the dominant biogeographical pattern.

PMID- 24688059
TI  - The histone chaperones Vps75 and Nap1 form ring-like, tetrameric structures in
      solution.
AB  - NAP-1 fold histone chaperones play an important role in escorting histones to and
      from sites of nucleosome assembly and disassembly. The two NAP-1 fold histone
      chaperones in budding yeast, Vps75 and Nap1, have previously been crystalized in
      a characteristic homodimeric conformation. In this study, a combination of small
      angle X-ray scattering, multi angle light scattering and pulsed electron-electron
      double resonance approaches were used to show that both Vps75 and Nap1 adopt ring
      shaped tetrameric conformations in solution. This suggests that the formation of
      homotetramers is a common feature of NAP-1 fold histone chaperones. The
      tetramerisation of NAP-1 fold histone chaperones may act to shield acidic
      surfaces in the absence of histone cargo thus providing a 'self-chaperoning' type
      mechanism. 

PMID- 24688060
TI  - Structural insights into RNA encapsidation and helical assembly of the Toscana
      virus nucleoprotein.
AB  - Toscana virus is an emerging bunyavirus in Mediterranean Europe where it accounts
      for 80% of pediatric meningitis cases during the summer. The negative-strand
      ribonucleic acid (RNA) genome of the virus is wrapped around the virally encoded
      nucleoprotein N to form the ribonucleoprotein complex (RNP). We determined
      crystal structures of hexameric N alone (apo) and in complex with a nonameric
      single-stranded RNA. RNA is sequestered in a sequence-independent fashion in a
      deep groove inside the hexamer. At the junction between two adjacent copies of
      Ns, RNA binding induced an inter-subunit rotation, which opened the RNA-binding
      tunnel and created a new assembly interface at the outside of the hexamer. Based
      on these findings, we suggest a structural model for how binding of RNA to N
      promotes the formation of helical RNPs, which are a characteristic hallmark of
      many negative-strand RNA viruses. 

PMID- 24688061
TI  - Carotid stent infection: a rare but potentially fatal complication of carotid
      artery stenting.
AB  - Infections involving endovascular devices are rare and, to our knowledge, only
      three cases of infection with an inserted carotid stent have ever been reported.
      A 68-year-old man underwent carotid artery stenting (CAS) of the left proximal
      internal carotid artery. Two days after CAS the patient developed a high fever
      and investigation showed that the inserted carotid stent was infected. The
      infection could not be controlled despite adequate antibiotic therapy. Eventually
      a rupture of the carotid artery occurred and the patient underwent emergency
      resection of the left carotid bifurcation in addition to stent removal and
      reconstruction with a saphenous vein interposition graft. The patient recovered
      fully without any neurological sequelae. 

PMID- 24688063
TI  - Neglected conditions: Neuroendocrine tumours.

PMID- 24688064
TI  - Neglected conditions: Sickle cell disease.

PMID- 24688065
TI  - Neglected conditions: Cardiac tumours.

PMID- 24688066
TI  - Neglected conditions: Oculopharyngeal muscular dystrophy.

PMID- 24688067
TI  - Stimulating intersubjective communication in an adult with deafblindness: a
      single-case experiment.
AB  - Sensory disabilities may limit a person's development of intersubjectivity, that
      is, the awareness of self and other, which develops in conjunction with
      interpersonal communication. This study used intersubjectivity theory to test a
      new intervention called the High-Quality Communication (HQC) intervention for its
      effects on a young adult with congenital deafblindness and a developmental age of
      between 1.5 and 4 years. Three of his social partners were trained to support
      attunement and meaning making with him through education and video feedback. This
      study measured seven observation categories at three layers of intersubjective
      development during a baseline and two intervention phases: dyadic interaction,
      shared emotion, referential communication, meaning negotiation, shared meaning,
      declarative communication, and shared past experience. The participant's use of
      conventional communication was included as an additional category. Effects were
      observed in all observation categories from the baseline to the intervention
      phases. Further study of the effectiveness of the HQC intervention is recommended
      to test whether effects generalize across people and settings. 

PMID- 24688068
TI  - Sign vocabulary in deaf toddlers exposed to sign language since birth.
AB  - Lexical comprehension and production is directly evaluated for the first time in
      deaf signing children below the age of 3 years. A Picture Naming Task was
      administered to 8 deaf signing toddlers (aged 2-3 years) who were exposed to Sign
      Language since birth. Results were compared with data of hearing speaking
      controls. In both deaf and hearing children, comprehension was significantly
      higher than production. The deaf group provided a significantly lower number of
      correct responses in production than did the hearing controls, whereas in
      comprehension, the 2 groups did not differ. Difficulty and ease of items in
      comprehension and production was similar for signing deaf children and hearing
      speaking children, showing that, despite size differences, semantic development
      followed similar paths. For signing children, predicates production appears
      easier than nominals production compared with hearing children acquiring spoken
      language. Findings take into account differences in input modalities and language
      structures. 

PMID- 24688069
TI  - Influence of enteric infections on response to oral poliovirus vaccine: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The impaired immunogenicity of oral poliovirus vaccine (OPV) in low
      income countries has been apparent since the early field trials of this vaccine.
      Infection with enteropathogens at the time of vaccination may contribute to this
      phenomenon. However, the relative influence of these infections on OPV
      performance remains uncertain. METHODS: We conducted a systematic review to
      examine the impact of concurrent enteric infections on OPV response. Using random
      effects models, we assessed the effects of nonpolio enteroviruses (NPEVs) and
      diarrhea on the odds of seroconversion and/or vaccine virus shedding. RESULTS: We
      identified 25 trials in which OPV outcomes were compared according to the
      presence or absence of enteric infections, the majority of which (n = 17)
      reported only on NPEVs. Concurrent NPEVs significantly reduced the odds of per
      dose seroconversion for type 1 poliovirus (odds ratio [OR] 0.44, 95% confidence
      interval 0.23-0.84), but not type 2 (OR 0.53 [0.19-1.46]) or type 3 (OR 0.56
      [0.27-1.12]). A similar reduction, significant for type 1 poliovirus (OR 0.50
      [0.28-0.89]), was observed in the odds of vaccine virus shedding among NPEV
      infected individuals. Concurrent diarrhea significantly inhibited per-dose
      seroconversion overall (OR 0.61 [0.38-0.87]). CONCLUSIONS: Our findings are
      consistent with an inhibitory effect of concurrent enteric infections on OPV
      response.

PMID- 24688070
TI  - Hemoglobinopathic erythrocytes affect the intraerythrocytic multiplication of
      Plasmodium falciparum in vitro.
AB  - BACKGROUND: The mechanisms by which alpha-thalassemia and sickle cell traits
      confer protection from severe Plasmodium falciparum malaria are not yet fully
      elucidated. We hypothesized that hemoglobinopathic erythrocytes reduce the
      intraerythrocytic multiplication of P. falciparum, potentially delaying the
      development of life-threatening parasite densities until parasite clearing
      immunity is achieved. METHODS: We developed a novel in vitro assay to quantify
      the number of merozoites released from an individual schizont, termed the
      "intraerythrocytic multiplication factor" (IMF). RESULTS: P. falciparum (3D7
      line) schizonts produce variable numbers of merozoites in all erythrocyte types
      tested, with median IMFs of 27, 27, 29, 23, and 23 in control, HbAS, HbSS, and
      alpha- and beta-thalassemia trait erythrocytes, respectively. IMF correlated
      strongly (r(2) = 0.97; P < .001) with mean corpuscular hemoglobin concentration,
      and varied significantly with mean corpuscular volume and hemoglobin content.
      Reduction of IMFs in thalassemia trait erythrocytes was confirmed using clinical
      parasite isolates with different IMFs. Mathematical modeling of the effect of IMF
      on malaria progression indicates that the lower IMF in thalassemia trait
      erythrocytes limits parasite density and anemia severity over the first 2 weeks
      of parasite replication. CONCLUSIONS: P. falciparum IMF, a parasite heritable
      virulence trait, correlates with erythrocyte indices and is reduced in
      thalassemia trait erythrocytes. Parasite IMF should be examined in other low
      indices erythrocytes.

PMID- 24688072
TI  - Torque Teno virus load as a biomarker of immunosuppression? New hopes and
      insights.

PMID- 24688071
TI  - Tumor necrosis factor alpha is associated with viral control and early disease
      progression in patients with HIV type 1 infection.
AB  - Inflammation in early human immunodeficiency virus type 1 (HIV-1) disease
      progression is not well characterized. Ninety patients with untreated primary HIV
      1 infection were studied to determine associations of inflammatory proteins with
      early disease progression. High plasma tumor necrosis factor alpha (TNF-alpha)
      levels (>=8.5 pg/mL) were significantly associated with an increased viral load
      set point and shorter times to reaching a CD4(+) T-cell count of <500 cells/mm(3)
      and initiating antiretroviral therapy. The increased risk of reaching a CD4(+) T
      cell count of <500 cells/mm(3) in the group with high TNF-alpha levels was driven
      by viral load but was independent of concurrent CD4(+) T-cell count. Thus, TNF
      alpha appears to be an important mediator of inflammation in patients with poor
      viral control and early HIV-1 disease progression.

PMID- 24688073
TI  - Molecular epidemiology of ascariasis: a global perspective on the transmission
      dynamics of Ascaris in people and pigs.
AB  - BACKGROUND: The roundworm Ascaris lumbricoides infects 0.8 billion people
      worldwide, and Ascaris suum infects innumerable pigs across the globe. The extent
      of natural cross-transmission of Ascaris between pig and human hosts in different
      geographical settings is unknown, warranting investigation. METHODS: Adult
      Ascaris organisms were obtained from humans and pigs in Europe, Africa, Asia, and
      Latin America. Barcodes were assigned to 536 parasites on the basis of sequence
      analysis of the mitochondrial cytochrome c oxidase I gene. Genotyping of 410
      worms was also conducted using a panel of microsatellite markers. Phylogenetic,
      population genetic, and Bayesian assignment methods were used for analysis.
      RESULTS: There was marked genetic segregation between worms originating from
      human hosts and those originating from pig hosts. However, human Ascaris
      infections in Europe were of pig origin, and there was evidence of cross
      transmission between humans and pigs in Africa. Significant genetic
      differentiation exists between parasite populations from different countries,
      villages, and hosts. CONCLUSIONS: In conducting an analysis of variation within
      Ascaris populations from pig and human hosts across the globe, we demonstrate
      that cross-transmission takes place in developing and developed countries,
      contingent upon epidemiological potential and local phylogeography. Our results
      provide novel insights into the transmission dynamics and speciation of Ascaris
      worms from humans and pigs that are of importance for control programs.

PMID- 24688075
TI  - Measles virus antibody responses in children randomly assigned to receive
      standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9
      months of age, or 9 and 18 months of age.
AB  - The World Health Organization recommends administration of measles vaccine (MV)
      at age 9 months in low-income countries. We tested the measles virus antibody
      response at 4.5, 9, 18, and 24 months of age for children randomly assigned to
      receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months, at 9 months, or
      at 9 and 18 months of age. At 4.5 months of age, 75% had nonprotective measles
      virus antibody levels. Following receipt of MV at 4.5 months of age, 77%
      (316/408) had protective antibody levels at 9 months of age; after a second dose
      at 9 months of age, 97% (326/337) had protective levels at 24 months of age. In
      addition, the response at both 9 and 24 months of age was inversely correlated
      with the antibody level at receipt of the first dose of MV, and the second dose
      of MV, received at 9 months of age, provided a significant boost in antibody
      level to children who had low antibody levels. In the group of 318 children who
      received MV at 9 months of age, with or without a second dose at 18 months of
      age, 99% (314) had protective levels at 24 months of age. The geometric mean
      titer at 24 months of age was significantly lower in the group that received MV
      at 4.5 and 9 months of age than in the group that received MV at 9 months of age
      (P = .0001). In conclusion, an early 2-dose MV schedule was associated with
      protective measles virus antibody levels at 24 months of age in nearly all
      children. Clinical Trials Registration. NCT00168558. 

PMID- 24688077
TI  - Queen Anne's lupus: phospholipids and the course of the empire.

PMID- 24688074
TI  - Elevated brain monoamine oxidase activity in SIV- and HIV-associated neurological
      disease.
AB  - We recently demonstrated direct evidence of increased monoamine oxidase (MAO)
      activity in the brain of a simian immunodeficiency virus (SIV) model of human
      immunodeficiency virus (HIV)-associated central nervous system (CNS) disease,
      consistent with previously reported dopamine deficits in both SIV and HIV
      infection. In this study, we explored potential mechanisms behind this elevated
      activity. MAO B messenger RNA was highest in macaques with the most severe SIV
      associated CNS lesions and was positively correlated with levels of CD68 and GFAP
      transcripts in the striatum. MAO B messenger RNA also correlated with viral loads
      in the CNS of SIV-infected macaques and with oxidative stress. Furthermore, in
      humans, striatal MAO activity was elevated in individuals with HIV encephalitis,
      compared with activity in HIV-seronegative controls. These data suggest that the
      neuroinflammation and oxidative stress caused by SIV infection in the CNS may
      provide the impetus for increased transcription of MAO B and that MAO, and more
      broadly, oxidative stress, have significant potential as therapeutic targets in
      CNS disease due to HIV.

PMID- 24688076
TI  - Torque Teno virus viremia correlates with intensity of maintenance
      immunosuppression in adult orthotopic liver transplant.

PMID- 24688078
TI  - Agent Orange and heart disease: is there a connection?

PMID- 24688080
TI  - Pulse oximetry in newborns with delayed cord clamping and immediate skin-to-skin
      contact.
AB  - OBJECTIVE: To assess whether defined reference ranges of oxygen saturation (SpO2)
      and heart rate (HR) of term infants after birth also apply for infants born after
      midwifery supervised uncomplicated vaginal birth, where delayed cord clamping
      (DCC) and immediate skin to skin contact (ISSC) is routine management. DESIGN:
      Prospective observational study. SETTING AND PATIENTS: Infants born vaginally
      after uncomplicated birth, that is, no augmentation, maternal pain relief or
      instrumental delivery. INTERVENTIONS: Midwives supervising uncomplicated birth at
      home or in hospital in the Leiden region (The Netherlands) used an oximeter and
      recorded SpO2 and HR in the first 10 min after birth. MAIN OUTCOME MEASURES: SpO2
      and HR values were compared to the international defined reference ranges.
      RESULTS: In Leiden, values of 109 infants were obtained and are comparable with
      previously defined reference ranges, except for a higher SpO2 (p<0.05) combined
      with a slower increase in the first 3 min. The Leiden cohort also had a lower HR
      (p<0.05) during the first 10 min with a slower increase in the first 3 min. In
      the first minutes after birth, tachycardia (HR>180 bpm) occurred less often, and
      a bradycardia (<80 bpm) more often (p<0.05). CONCLUSIONS: Defined reference
      ranges can be used in infants born after uncomplicated vaginal birth with DCC and
      ISSC, but higher SpO2 and lower HR were observed in the first minutes.

PMID- 24688079
TI  - Common drugs inhibit human organic cation transporter 1 (OCT1)-mediated
      neurotransmitter uptake.
AB  - The human organic cation transporter 1 (OCT1) is a polyspecific transporter
      involved in the uptake of positively charged and neutral small molecules in the
      liver. To date, few endogenous compounds have been identified as OCT1 substrates;
      more importantly, the effect of drugs on endogenous substrate transport has not
      been examined. In this study, we established monoamine neurotransmitters as
      substrates for OCT1, specifically characterizing serotonin transport in human
      embryonic kidney 293 cells. Kinetic analysis yielded a Km of 197 micomolar and a
      Vmax of 561 pmol/mg protein/minute for serotonin. Furthermore, we demonstrated
      that serotonin uptake was inhibited by diphenhydramine, fluoxetine, imatinib, and
      verapamil, with IC50 values in the low micromolar range. These results were
      recapitulated in primary human hepatocytes, suggesting that OCT1 plays a
      significant role in hepatic elimination of serotonin and that xenobiotics may
      alter the elimination of endogenous compounds as a result of interactions at the
      transporter level. 

PMID- 24688081
TI  - Benefit-finding intervention for Alzheimer caregivers: conceptual framework,
      implementation issues, and preliminary efficacy.
AB  - PURPOSE: To describe an intervention promoting benefit-finding in Alzheimer
      caregivers, to discuss key issues in implementation and ways to resolve them, and
      to examine whether the intervention reduced burden and depression in a small
      randomized trial. DESIGN AND METHODS: Twenty-five caregivers were randomized into
      benefit-finding and psychoeducation groups. Both groups had eight weekly
      sessions. Outcome measures including role overload, Zarit Burden Interview, and
      Hamilton depression scale were collected at baseline and after treatment. Results
      were analyzed using analysis of covariance. Additionally, the challenges of
      implementing such interventions, some of which related to cultural issues, were
      analyzed qualitatively. RESULTS: Controlling for pretest, the benefit-finding
      group had lower depression than the psychoeducation group at post-test, despite
      the fact that some caregivers found benefit-finding challenging. The two groups
      did not differ on overload and burden. However, within-group analysis suggested
      that both groups showed significant reductions in overload from pretest to post
      test. In addition, we discussed participants' difficulties in grasping the
      technique of thought modification for benefit-finding, recording such exercises
      at home, and sharing their thoughts and experiences in groups. We described
      measures undertaken in the main trial to overcome these issues. IMPLICATIONS:
      Cognitive approaches focusing on benefit-finding are feasible among Chinese
      caregivers, with preliminary evidence suggesting an effect on alleviating
      depression.

PMID- 24688082
TI  - Comparison of Long-term Care in Nursing Homes Versus Home Health: Costs and
      Outcomes in Alabama.
AB  - PURPOSE OF THE STUDY: To compare acute care outcomes and costs among nursing home
      residents with community-dwelling home health recipients. DESIGN AND METHODS: A
      matched retrospective cohort study of Alabamians aged more than or equal to 65
      years admitted to a nursing home or home health between March 31, 2007 and
      December 31, 2008 (N = 1,291 pairs). Medicare claims were compared up to one year
      after admission into either setting. Death, emergency department and inpatient
      visits, inpatient length of stay, and acute care costs were compared using t
      tests. Medicaid long-term care costs were compared for a subset of matched
      beneficiaries. RESULTS: After one year, 77.7% of home health beneficiaries were
      alive compared with 76.2% of nursing home beneficiaries (p < .001). Home health
      beneficiaries averaged 0.2 hospital visits and 0.1 emergency department visits
      more than nursing home beneficiaries, differences that were statistically
      significant. Overall acute care costs were not statistically different; home
      health beneficiaries' costs averaged $31,423, nursing home beneficiaries' $32,239
      (p = .5032). Among 426 dual-eligible pairs, Medicaid long-term care costs
      averaged $4,582 greater for nursing home residents (p < .001). IMPLICATIONS:
      Using data from Medicare claims, beneficiaries with similar functional status,
      medical diagnosis history, and demographics had similar acute care costs
      regardless of whether they were admitted to a nursing home or home health care.
      Additional research controlling for exogenous factors relating to long-term care
      decisions is needed.

PMID- 24688083
TI  - Efficacy of everolimus in patients with advanced renal cell carcinoma refractory
      or intolerant to VEGFR-TKIs and safety compared with prior VEGFR-TKI treatment.
AB  - OBJECTIVE: Everolimus is positioned as second-line treatment for metastatic renal
      cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine
      kinase inhibitors. We investigated retrospectively the efficacy and safety of
      everolimus in Japanese patients with advanced renal cell carcinoma in the
      clinical setting. METHODS: Nineteen patients who discontinued treatment with
      vascular endothelial growth factor receptor-tyrosine kinase inhibitors because of
      disease progression or adverse events were administered everolimus. We evaluated
      progression-free survival, overall survival and tumor response rate of everolimus
      treatment. We also compared laboratory abnormalities and adverse events of
      everolimus treatment with those of prior vascular endothelial growth factor
      receptor-tyrosine kinase inhibitors therapy. RESULTS: In all patients, median
      progression-free survival was 8.4 months and median overall survival was not
      reached at 25 months. The best objective response was complete response in 1
      patient and stable disease in 15 patients. Eleven patients (58%) were intolerant
      and 8 (42%) were refractory to prior vascular endothelial growth factor receptor
      tyrosine kinase inhibitors treatment. Median overall survival was significantly
      longer (P < 0.01) in vascular endothelial growth factor receptor-tyrosine kinase
      inhibitor-intolerant (>25 months) than in vascular endothelial growth factor
      receptor-tyrosine kinase inhibitor-refractory subjects (4.3 months), and median
      progression-free survival tended to be better (P= 0.06) in vascular endothelial
      growth factor receptor-tyrosine kinase inhibitor-intolerant (10.0 months) than in
      vascular endothelial growth factor receptor-tyrosine kinase inhibitor-refractory
      subjects (2.5 months). Two patients discontinued everolimus treatment because of
      adverse events. CONCLUSIONS: In this study, the overall survival and progression
      free survival were better in vascular endothelial growth factor receptor-tyrosine
      kinase inhibitor-intolerant than in vascular endothelial growth factor receptor
      tyrosine kinase inhibitor-refractory subjects. The adverse event profiles of
      everolimus and vascular endothelial growth factor receptor-tyrosine kinase
      inhibitors were different. Patients intolerant to vascular endothelial growth
      factor receptor-tyrosine kinase inhibitors may tolerate everolimus well and have
      greater survival benefit from switching to everolimus than those refractory to
      vascular endothelial growth factor receptor-tyrosine kinase inhibitors.

PMID- 24688084
TI  - Concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF)
      in patients with locally advanced squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: Compared with radiotherapy alone, concurrent chemoradiotherapy
      significantly improves survival rates for patients with squamous cell carcinoma
      of the head and neck. The aim of this study was to retrospectively evaluate the
      efficacy, toxicity and long-term prognosis of concurrent chemoradiotherapy with
      docetaxel, cisplatin and 5-fluorouracil chemotherapy. METHODS: A total of 140
      patients were enrolled and evaluated. Patients were received two cycles of
      docetaxel, cisplatin and 5-fluorouracil chemotherapy (docetaxel [50 mg/m(2): Day
      1], cisplatin [60 mg/m(2): Day 4] and continuous 5-fluorouracil [600 mg/m(2)/day:
      Days 1-5]) during definitive radiotherapy. RESULTS: The overall response rate was
      97.1%. The 3 and 5-year overall survival rates were 83.3 and 79.2%, respectively.
      The 3 and 5-year disease-specific survival rates were 84.2 and 80.0%,
      respectively. Among patients with laryngeal or hypopharyngeal carcinoma, the 5
      year laryngectomy-free survival rate was 64.9%. CONCLUSIONS: Concurrent
      chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil showed excellent
      survival and organ preservation rates for the patients with locally advanced
      squamous cell carcinoma of the head and neck.

PMID- 24688085
TI  - Effect of HMB/Arg/Gln on the prevention of radiation dermatitis in head and neck
      cancer patients treated with concurrent chemoradiotherapy.
AB  - OBJECTIVE: This prospective randomized Phase II study was designed to evaluate
      the preventive effect of an oral nutrition supplement composed of beta-hydroxy
      beta-methylbutyrate, arginine and glutamine (beta-hydroxy-beta
      methylbutyrate/arginine/glutamine) on radiation dermatitis in head and neck
      cancer patients. METHODS: Forty patients with histologically proven head and neck
      cancer, treated with concurrent chemoradiotherapy involving cisplatin were
      recruited. They were randomly assigned to the beta-hydroxy-beta
      methylbutyrate/arginine/glutamine supplement treatment group (Group A) or the
      control group that received no supplement (Group B). The primary endpoint of this
      study was the percentage of patients developing >=Grade 3 dermatitis. The
      secondary endpoints were the percentage of patients developing >=Grade 2
      dermatitis, and the duration of each grade of dermatitis relative to the
      observation period. RESULTS: The incidence of >=Grade 3 dermatitis did not differ
      between the two groups. However, as secondary endpoints of this study, the
      incidence of >=Grade 2 dermatitis was lower in Group A than B (62.6 vs. 94.4%; P
      < 0.05), and the duration of >=Grade 1 dermatitis was shorter in Group A than B
      (44.8 vs. 56.7%; P < 0.01), as was the duration of >=Grade 2 dermatitis (16.5 vs.
      26.5%; P < 0.05). CONCLUSIONS: Our study indicated that beta-hydroxy-beta
      methylbutyrate/arginine/glutamine supplementation was potentially effective in
      the prevention of radiation dermatitis in head and neck cancer patients.

PMID- 24688086
TI  - Secondary EML4-ALK-positive lung adenocarcinoma in a patient previously treated
      for acute lymphoblastic leukemia in childhood: a case report.
AB  - It is widely recognized that the risk of secondary neoplasms increases as
      childhood cancer survivors progress through adulthood. These are mainly
      hematological malignancies, and recurrent chromosome translocations are commonly
      detected in such cases. On the other hand, while secondary epithelial
      malignancies have sometimes been reported, chromosome translocations in these
      epithelial malignancies have not. A 33-year-old man who had been diagnosed with
      acute lymphoblastic leukemia and treated with chemotherapy almost 20 years
      earlier was diagnosed with lung adenocarcinoma. After chromosomal rearrangement
      of echinoderm microtubule-associated protein-like 4 gene and the anaplastic
      lymphoma kinase gene was detected in this adenocarcinoma, he responded to
      treatment with crizotinib. It was therefore concluded that this echinoderm
      microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase gene
      positive lung adenocarcinoma was a secondary epithelial malignancy. 

PMID- 24688087
TI  - Phase I study of carboplatin combined with pemetrexed for elderly patients with
      advanced non-squamous non-small cell lung cancer.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the safety and
      tolerability of carboplatin plus pemetrexed for elderly patients (>=75 years)
      with chemotherapy-naive advanced non-squamous non-small cell lung cancer.
      METHODS: Patients received escalated doses of carboplatin at an area under the
      concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500
      mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided
      according to whether dose-limiting toxicity occurred in the first cycle of
      chemotherapy. RESULTS: A total of 20 patients (6 at Level 1, 14 at Level 2) were
      enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the
      first six patients at Level 2, and therefore the combination of carboplatin at an
      area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was
      considered to be the recommended dose. Among a total of 14 patients in Level 2,
      only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia
      and urticaria. The major toxicities were neutropenia, thrombocytopenia and
      anemia. Liver dysfunction, fatigue and anorexia were also common, but generally
      manageable. Six patients showed partial responses, giving the overall response
      rate of 30%. The median progression-free survival period was 4.8 months (95%
      confidence interval 2.9-6.7 months). CONCLUSIONS: The combination of carboplatin
      at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2)
      was determined as the recommended dose in chemotherapy-naive elderly patients
      (>=75 years) with advanced non-squamous non-small cell lung cancer, in view of
      overall safety and tolerability.

PMID- 24688088
TI  - Measurement of perceptions of educational environment in evidence-based medicine.
AB  - In recent years, there has been a renewed interest in measuring perceptions
      regarding different aspects of the medical educational environment. A reliable
      tool was developed for measuring perceptions of the educational environment as it
      relates to evidence-based medicine as part of a multicountry randomised
      controlled trial to evaluate the effectiveness of a clinically integrated
      evidence-based medicine course. Participants from 10 specialties completed the
      questionnaire. A working dataset of 518 observations was available. Two
      independent subsets of data were created for conducting an exploratory factor
      analysis (n=244) and a confirmatory factor analysis (n=274), respectively. The
      exploratory factor analysis yielded five 67-item definitive instruments, with
      five to nine dimensions; all resulted in acceptable explanations of the total
      variance (range 56.6-65.9%). In the confirmatory factor analysis phase, all
      goodness of-fit measures were acceptable for all models (root mean square error
      of approximation <= 0.047; comparative fit index >= 0.980; normed chi(2) <=
      1.647; Bentler-Bonett normed fit index >= 0.951). The authors selected the
      factorisation with seven dimensions (factor-7 instrument) as the most useful on
      pragmatic grounds and named it Evidence-Based Medicine Educational Environment
      Measure 67 (EBMEEM-67). Cronbach's alpha for subscales ranged between 0.81 and
      0.93. The subscales are: 'Knowledge and learning materials'; 'Learner support';
      'General relationships and support'; 'Institutional focus on EBM'; 'Education,
      training and supervision'; 'EBM application opportunities'; and 'Affirmation of
      EBM environment'. The EBMEEM-67 can be a useful diagnostic and benchmarking tool
      for evaluating the perceptions of residents of the environment in which evidence
      based medicine education takes place.

PMID- 24688089
TI  - Physician antibiotic prescriptions for skin infections in the outpatient setting
      are often unnecessarily long and include unnecessary antibiotics.

PMID- 24688090
TI  - In the absence of diagnosed concussion in collegiate contact sport athletes, a
      relationship is suggested between the effects of head impact exposure, white
      matter diffusivity measures and cognition.

PMID- 24688091
TI  - Continuation-phase cognitive therapy and fluoxetine are effective in reducing the
      risk of relapse/recurrence in major depression after incomplete remission.

PMID- 24688092
TI  - Implications of the E-selectin S128R mutation for drug discovery.
AB  - The C-type lectin E-selectin mediates the rolling of circulating leukocytes on
      vascular endothelial cells during the inflammatory process. In numerous studies,
      the S128R mutation of the E-selectin was associated with cardiovascular and
      autoimmune diseases. There is evidence that the S128R E-selectin mutation leads
      to a loss in ligand specificity, thus increasing leukocyte recruitment. Apart
      from the natural tetrasaccharide ligand sialyl Lewis(x) (sLe(x)), it has
      previously been proposed that non-fucosylated carbohydrates also bind to S128R E
      selectin. To evaluate the therapeutic potential of the antagonism of the E
      selectin mutant, ligand specificity was reinvestigated on a molecular basis. We
      determined the ligand specificity of wild-type and S128R E-selectin in a target
      based competitive assay, a glycan array screen and cell-based binding assays
      under static and flow conditions. Regarding ligand-specificity, the binding
      properties of S128R E-selectin were identical to those of wt E-selectin, i.e., no
      mutant-specific binding of 3'-sialyl-N-acetyllactosamine, heparin, fetuin and
      K562 cells was observed. Additionally, the binding affinities of glycomimetic E
      selectin antagonists were identical for wt and S128R E-selectin. Overall, the
      previous reports on carbohydrate ligand promiscuity of S128R E-selectin could not
      be confirmed. 

PMID- 24688093
TI  - Structure of the K2 capsule associated with the KL2 gene cluster of Acinetobacter
      baumannii.
AB  - The repeat unit structure of the K2 capsule from an extensively antibiotic
      resistant Acinetobacter baumannii global clone 2 (GC2) strain was determined. The
      oligosaccharide contains three simple sugars, d-glucopyranose, d-galatopyranose
      and N-acetyl-d-galactosamine, and the complex sugar, 5,7-diacetamido-3,5,7,9
      tetradeoxy-l-glycero-l-manno-non-2-ulosonic acid (Pse5Ac7Ac or pseudaminic acid),
      which has not previously been reported in any A. baumannii capsule. The strain
      was found to carry all the genes required for the synthesis of the sugars and
      construction of the K2 structure. The linkages catalyzed by the initiating
      transferase, three glycosyltransferases and the Wzy polymerase were also
      predicted. Examination of publicly available A. baumannii genome sequences
      revealed that the same gene cluster, KL2, often occurs in extensively antibiotic
      resistant GC2 isolates and in further strain types. The gene module responsible
      for the synthesis of pseudaminic acid was also detected in four other K loci. A
      related module including genes for an acylated relative of pseudaminic acid was
      also found in two new KL types. A polymerase chain reaction scheme was developed
      to detect all modules containing genes for sugars based on pseudaminic acid and
      to specifically detect KL2. 

PMID- 24688095
TI  - Unusual chest radiographic findings in children.

PMID- 24688094
TI  - A Burkholderia cenocepacia MurJ (MviN) homolog is essential for cell wall
      peptidoglycan synthesis and bacterial viability.
AB  - The cell wall peptidoglycan (PG) of Burkholderia cenocepacia, an opportunistic
      pathogen, has not yet been characterized. However, the B. cenocepacia genome
      contains homologs of genes encoding PG biosynthetic functions in other bacteria.
      PG biosynthesis involves the formation of the undecaprenyl-pyrophosphate-linked N
      acetyl glucosamine-N-acetyl muramic acid-pentapeptide, known as lipid II, which
      is built on the cytosolic face of the cell membrane. Lipid II is then
      translocated across the membrane and its glycopeptide moiety becomes incorporated
      into the growing cell wall mesh; this translocation step is critical to PG
      synthesis. We have investigated candidate flippase homologs of the MurJ family in
      B. cenocepacia. Our results show that BCAL2764, herein referred to as murJBc, is
      indispensable for viability. Viable B. cenocepacia could only be obtained through
      a conditional mutagenesis strategy by placing murJBc under the control of a
      rhamnose-inducible promoter. Under rhamnose depletion, the conditional strain
      stopped growing and individual cells displayed morphological abnormalities
      consistent with a defect in PG synthesis. Bacterial cells unable to express
      MurJBc underwent cell lysis, while partial MurJBc depletion sensitized the mutant
      to the action of beta-lactam antibiotics. Depletion of MurJBc caused accumulation
      of PG precursors consistent with the notion that this protein plays a role in
      lipid II flipping to the periplasmic compartment. Reciprocal complementation
      experiments of conditional murJ mutants in B. cenocepacia and Escherichia coli
      with plasmids expressing MurJ from each strain indicated that MurJBc and MurJEc
      are functional homologs. Together, our results are consistent with the notion
      that MurJBc is a PG lipid II flippase in B. cenocepacia. 

PMID- 24688096
TI  - Myelopathy among zinc-smelter workers in Upper Silesia during the late 19th
      century.
AB  - Zinc-induced myeloneuropathy was recently (re)discovered and its pathophysiology
      elaborated as resulting from secondary copper deficiency. However, myelopathy was
      a recognized problem among European zinc-smelter workers in the late 19th
      century, although these early reports have been overlooked in recent studies and
      reports. The purpose of this article is to translate and review German-language
      reports of myelopathy among zinc-smelter workers in Upper Silesia (now southern
      Poland) by Schlockow from the 1870s. Disease manifestations among zinc-smelter
      workers developed after sustained zinc exposure over many years. The earliest
      symptoms were sensory and included paresthesias, dysesthesias, allodynia, and
      formication in the lower extremities, particularly the feet. Workers ultimately
      developed a clinical picture resembling subacute combined degeneration of the
      spinal cord with a spastic-ataxic gait with prominent proprioceptive impairment,
      sensory disequilibrium, and rombergism. 

PMID- 24688097
TI  - Reversible leukoencephalopathy in sodium monofluoroacetate intoxication.

PMID- 24688098
TI  - Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of
      Memory Study.

PMID- 24688099
TI  - Antithrombotic drugs and risk of hemorrhagic stroke in the general population.

PMID- 24688101
TI  - Journal Club: surveillance neuroimaging and neurologic examinations affect care
      for intracerebral hemorrhage.

PMID- 24688102
TI  - Teaching NeuroImages: internal carotid artery dissection presenting as Villaret
      syndrome.

PMID- 24688103
TI  - The role of lipolysis in human orosensory fat perception.
AB  - Taste perception elicited by food constituents and facilitated by sensory cells
      in the oral cavity is important for the survival of organisms. In addition to the
      five basic taste modalities, sweet, umami, bitter, sour, and salty, orosensory
      perception of stimuli such as fat constituents is intensely investigated.
      Experiments in rodents and humans suggest that free fatty acids represent a major
      stimulus for the perception of fat-containing food. However, the lipid fraction
      of foods mainly consists of triglycerides in which fatty acids are esterified
      with glycerol. Whereas effective lipolysis by secreted lipases (LIPs) liberating
      fatty acids from triglycerides in the rodent oral cavity is well established, a
      similar mechanism in humans is disputed. By psychophysical analyses of humans, we
      demonstrate responses upon stimulation with triglycerides which are attenuated by
      concomitant LIP inhibitor administration. Moreover, lipolytic activities detected
      in minor salivary gland secretions directly supplying gustatory papillae were
      correlated to individual sensitivities for triglycerides, suggesting that
      differential LIP levels may contribute to variant fat perception. Intriguingly,
      we found that the LIPF gene coding for lingual/gastric LIP is not expressed in
      human lingual tissue. Instead, we identified the expression of other LIPs, which
      may compensate for the absence of LIPF.

PMID- 24688104
TI  - RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma
      patients.
AB  - BACKGROUND: Retinoblastoma (Rb) is a childhood cancer of the retina, commonly
      initiated by biallelic inactivation of the RB1 gene. Knowledge of the presence of
      a heritable RB1 mutation can help in risk management and reproductive decision
      making. We report here on RB1 mutation scanning in a unique nationwide cohort of
      Rb patients from the Netherlands. METHODS: From the 1173 Rb patients registered
      in the Dutch National Retinoblastoma Register until January 2013, 529 patients
      from 433 unrelated families could be included. RB1 mutation scanning was
      performed with different detection methods, depending on the time period.
      RESULTS: Our mutation detection methods revealed RB1 mutations in 92% of
      bilateral and/or familial Rb patients and in 10% of non-familial unilateral
      cases. Overall an RB1 germline mutation was detected in 187 (43%) of 433 Rb
      families, including 33 novel mutations. The distribution of the type of mutation
      was 37% nonsense, 20% frameshift, 21% splice, 9% large indel, 5% missense, 7%
      chromosomal deletions and 1% promoter. Ten per cent of patients were mosaic for
      the RB1 mutation. Six three-generation families with incomplete penetrance RB1
      mutations were found. We found evidence that two variants, previously described
      as pathogenic RB1 mutations, are likely to be neutral variants. CONCLUSIONS: The
      frequency of the type of mutations in the RB1 gene in our unbiased national
      cohort is the same as the mutation spectrum described worldwide. Furthermore, our
      RB1 mutation detection regimen achieves a high scanning sensitivity.

PMID- 24688105
TI  - Immune suppression for childhood acquired aplastic anemia and myelodysplastic
      syndrome: where next?

PMID- 24688106
TI  - Assessing the prognostic impact of immune cell infiltrates in follicular
      lymphoma.

PMID- 24688107
TI  - Understanding antifungal prophylaxis with posaconazole in hematology patients: an
      evolving bedside to bench story.

PMID- 24688108
TI  - Understanding the multiple biological aspects leading to myeloma.

PMID- 24688109
TI  - Why methylation is not a marker predictive of response to hypomethylating agents.
AB  - The azanucleotides azacitidine and decitabine have been shown to induce
      hematologic response and prolong survival in higher-risk myelodysplastic
      syndromes. They are inhibitors of DNA methyltransferase-1 and induce DNA
      hypomethylation. Induction of apoptosis is also clinically relevant, in
      particular during the first treatment cycles, when cytopenia is a frequent side
      effect. Since the hypomethylating effect is reversible, and the malignant clone
      has been shown to persist in most responding patients, several cycles are
      necessary to achieve and maintain responses, while treatment interruption is
      associated with rapid relapse. Methylation studies have shown global and gene
      specific hypermethylation in myelodysplastic syndromes, but there seems to be
      little relation between the degree of demethylation following hypomethylating
      treatment and hematologic response. The presence of concurrent genomic
      hypermethylation and hypomethylation may impair the predictive power of current
      detection techniques. This scenario has been complicated by the identification of
      epigenetic enzyme mutations, including TET2, IDH1/2, DNMT3A and EZH2, which are
      important for response to hypomethylating treatment. Changes in azanucleotide
      metabolism genes may also play a role. In the future, methylation analysis
      concentrating not only on promoters, but also on gene bodies and intergenic
      regions, may identify key genes in patients with the highest probability of
      response to azanucleotides and allow a patient-tailored approach. 

PMID- 24688112
TI  - Remembering professor Roberto Stasi (August 24th 1961 - January 28th 2014).

PMID- 24688111
TI  - The role of positron emission tomography-computed tomography and magnetic
      resonance imaging in diagnosis and follow up of multiple myeloma.
AB  - Multiple myeloma is the second most common hematologic malignancy and occurs most
      commonly in elderly patients. Almost all multiple myeloma patients develop bone
      lesions in the course of their disease or have evidence of bone loss at initial
      diagnosis. Whole-body conventional radiography remains the gold standard in the
      diagnostic evaluation, but computed tomography, magnetic resonance imaging and
      18F-fluorodeoxyglucose positron emission tomography are increasingly used as
      complementary techniques in the detection of bone lesions. Moreover, the number
      of lesions detected and the presence of extramedullary disease give strong
      prognostic information. These new techniques may help to assess treatment
      response in solitary plasmacytoma or in multiple myeloma. In this article, we
      review recent data on the different imaging techniques used at diagnosis and in
      the assessment of treatment response, and discuss some current issues. 

PMID- 24688110
TI  - Primary thrombocytosis in children.
AB  - Myeloproliferative neoplasms are uncommon disorders in children, for which we
      have limited understanding of the pathogenesis and optimal management. JAK2 and
      MPL mutations, while common drivers of myeloproliferative neoplasms in adult
      patients, are not clearly linked to pediatric disease. Management and clinical
      outcomes in adults have been well delineated with defined recommendations for
      risk stratification and treatment. This is not the case for pediatric patients,
      for whom there is neither a standard approach to workup nor any consensus
      regarding management. This review will discuss thrombocytosis in children,
      including causes of thrombocytosis in children, the limited knowledge we have
      regarding pediatric primary thrombocytosis, and our thoughts on potential risk
      stratification and management, and future questions to be answered by laboratory
      research and collaborative clinical study. 

PMID- 24688113
TI  - The ecology of sexual health of sexual minorities in Guatemala City.
AB  - Guatemalan gay and bisexual men, men who have sex with men (MSM), and transgender
      persons carry disproportionate burden of HIV and other sexually transmitted
      infections compared with other Guatemalan subgroups. However, little is known
      about the determinants of sexual health to inform health promotion and disease
      prevention interventions among these sexual minorities. We sought to explore
      sexual health and HIV risk among Guatemalan sexual minorities, using a community
      based participatory research approach. We conducted 8 focus groups (n = 87
      participants total) and 10 individual in-depth interviews with gay and bisexual
      men, MSM, and transgender persons. Using constant comparison, an approach to
      grounded theory, we analyzed verbatim transcripts and identified 24 themes that
      we organized into five ecological factors influencing sexual health:
      intrapersonal (e.g. misconceptions about HIV transmission, low perceived
      susceptibility and lack of condoms use skills); interpersonal (e.g. family
      rejection and condom use as a barrier to intimacy); community (e.g.
      discrimination and stigma); institutional (e.g. limited access to health
      promotion resources); and public policy (e.g. perceived lack of provider
      confidentiality and anti-gay rhetoric). There is profound need for multiple-level
      interventions to ensure that Guatemalan sexual minorities have the knowledge and
      skills needed to reduce sexual risk. Interventions are warranted to increase
      social support among sexual minorities, reduce negative perspectives about sexual
      minorities, develop institutional resources to meet the needs of sexual
      minorities and reduce harmful anti-gay rhetoric. Understanding and intervening on
      the identified factors is especially important given that the health of
      Guatemalan sexual minorities has been to-date neglected. 

PMID- 24688114
TI  - Quality of online information on type 2 diabetes: a cross-sectional study.
AB  - Evidence-based health information is a prerequisite for patients with type 2
      diabetes to engage in self-management and to make informed medical decisions. The
      Internet is an important source of health information. In the present study, we
      systematically assessed formal quality, quality of decision support and usability
      of German and English language websites on type 2 diabetes. The search term 'type
      2 diabetes' was entered in the two most popular search engines. Descriptive data
      on website quality are presented. Additionally, associations between website
      quality and affiliation (commercial vs. non-commercial), presence of the HON code
      quality seal and website traffic were explored. Forty-six websites were included.
      Most websites provided basic information necessary for decision-making, while
      only one website also provided decision support. Websites with a HON code had
      significantly better formal quality than websites without HON code. We found a
      highly significant correlation between usability and website traffic and a
      significant correlation between formal quality and website traffic. Most websites
      do not provide sufficient information to support patients in medical decision
      making. Our finding that usability and website traffic are tightly associated is
      consistent with previous research indicating that design is the most important
      cue for users assessing website credibility. 

PMID- 24688115
TI  - 2014 ACC/AHA valve guidelines: earlier intervention for chronic mitral
      regurgitation.

PMID- 24688117
TI  - Abnormal retinal development associated with FRMD7 mutations.
AB  - Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder,
      often associated with FRMD7 mutations. As the appearance of the retina is
      reported to be normal based on conventional fundus photography, IIN is postulated
      to arise from abnormal cortical development. To determine whether the afferent
      visual system is involved in FRMD7 mutations, we performed in situ hybridization
      studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks
      post-conception). We show a dynamic retinal expression pattern of FRMD7 during
      development. We observe expression within the outer neuroblastic layer, then in
      the inner neuroblastic layer and at 9 weeks post-conception a bilaminar
      expression pattern. Expression was also noted within the developing optic stalk
      and optic disk. We identified a large cohort of IIN patients (n = 100), and
      performed sequence analysis which revealed 45 patients with FRMD7 mutations.
      Patients with FRMD7 mutations underwent detailed retinal imaging studies using
      ultrahigh-resolution optical coherence tomography. The tomograms were compared
      with a control cohort (n = 60). The foveal pit was significantly shallower in
      FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with
      significantly decreased optic disk area, retinal nerve fiber layer thickness, cup
      area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first
      time that abnormal afferent system development is associated with FRMD7 mutations
      and could be an important etiological factor in the development of nystagmus. 

PMID- 24688119
TI  - Danger signals from ATP and adenosine in pregnancy and preeclampsia.

PMID- 24688118
TI  - Risk of endometrial, ovarian and breast cancer in women with polycystic ovary
      syndrome: a systematic review and meta-analysis.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition affecting ~8%
      of women. The objective of the present study was to quantify separately the risk
      of endometrial cancer, ovarian cancer and breast cancer in women with PCOS
      compared with non-PCOS controls, and quantify separately the risk to women of all
      ages as well as the risk to premenopausal women. METHODS: We conducted a
      systematic review and meta-analysis of observational studies. Studies were
      eligible for inclusion if they compared women with PCOS to non-PCOS groups for
      fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE
      published up to 7 October 2013 in any language were identified, and relevant
      papers were also searched by hand. Relevant data (for example, study design,
      source of control data, diagnostic criteria) were extracted and tabulated.
      RESULTS: From 698 references, 11 studies (5 of endometrial cancer and 3 each of
      ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919
      women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method,
      with fixed or random effects model as appropriate, women with PCOS were at a
      significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95%
      confidence interval (CI), 1.31-5.95, P < 0.008), but the risk of ovarian and
      breast cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P <
      0.11 and OR, 0.95; 95% CI, 0.64-1.39, P < 0.78, respectively). However when
      studies which included women aged over 54 years were excluded from the analysis,
      the risk for women with PCOS increased further for endometrial cancer (OR, 4.05;
      95% CI, 2.42-6.76, P < 0.00001), became significantly increased for ovarian
      cancer (OR, 2.52; 95% CI, 1.08-5.89, P < 0.03), but remained non-significant for
      breast cancer (OR, 0.78; 95% CI, 0.46-1.32, P < 0.35). CONCLUSIONS: This is the
      first meta-analysis to examine gynaecological cancers in women with PCOS younger
      than 54 years of age compared with controls of similar age. Current data suggest
      that women of all ages with PCOS are at an increased risk of endometrial cancer
      but the risk of ovarian and breast cancer was not significantly increased
      overall. These results highlight the potential risk of gynaecological cancer
      morbidities associated with PCOS. However, the available evidence is far from
      robust and variation in diagnostic criteria for PCOS, associated risk factors
      (particularly obesity), and selection bias in the studies may have resulted in an
      exaggeration of the increased risk. Furthermore, women who have PCOS should also
      be made aware that any increased risk for endometrial cancer must be judged in
      the context of its relatively low incidence in the general population. A large
      well-controlled prospective study is required in order to gain a more accurate
      estimate of the risk of gynaecological cancers in women with PCOS. PROSPERO CRD
      REGISTRATION NUMBER: CRD42012003500.

PMID- 24688116
TI  - Genome-wide association meta-analysis of human longevity identifies a novel locus
      conferring survival beyond 90 years of age.
AB  - The genetic contribution to the variation in human lifespan is ~ 25%. Despite the
      large number of identified disease-susceptibility loci, it is not known which
      loci influence population mortality. We performed a genome-wide association meta
      analysis of 7729 long-lived individuals of European descent (>= 85 years) and 16
      121 younger controls (<65 years) followed by replication in an additional set of
      13 060 long-lived individuals and 61 156 controls. In addition, we performed a
      subset analysis in cases aged >= 90 years. We observed genome-wide significant
      association with longevity, as reflected by survival to ages beyond 90 years, at
      a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P = 1.74 * 10(-8)). We
      also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P =
      3.40 * 10(-36)), representing the TOMM40/APOE/APOC1 locus. In a prospective meta
      analysis (n = 34 103), the minor allele of rs2149954 (T) on chromosome 5q33.3
      associates with increased survival (HR = 0.95, P = 0.003). This allele has
      previously been reported to associate with low blood pressure in middle age.
      Interestingly, the minor allele (T) associates with decreased cardiovascular
      mortality risk, independent of blood pressure. We report on the first GWAS
      identified longevity locus on chromosome 5q33.3 influencing survival in the
      general European population. The minor allele of this locus associates with low
      blood pressure in middle age, although the contribution of this allele to
      survival may be less dependent on blood pressure. Hence, the pleiotropic
      mechanisms by which this intragenic variation contributes to lifespan regulation
      have to be elucidated.

PMID- 24688120
TI  - New therapy via targeting androgen receptor in monocytes/macrophages to battle
      atherosclerosis.
AB  - The male sex has a higher risk to develop coronary artery diseases, including
      atherosclerosis. The androgen receptor (AR) is expressed in several
      atherosclerosis-associated cell types, including monocytes/macrophages,
      endothelial cells (ECs), and smooth muscle cells (SMCs), but its
      pathophysiological role in each cell type during the development of
      atherosclerotic lesions remains unclear. Using the Cre-loxP system, we
      selectively knocked out AR in these 3 cell types and the resultant AR knockout
      (ARKO) mice, monocyte/macrophage ARKO, EC-ARKO, and SMC-ARKO, were then crossed
      with the low-density lipoprotein receptor (LDLR) deficient (LDLR(-/-)) mice to
      develop monocyte/macrophage ARKO-LDLR(-/-), EC-ARKO-LDLR(-/-), and SMC-ARKO-LDLR(
      /-) mice for the study of atherosclerosis. The results showed that the
      monocyte/macrophage ARKO-LDLR(-/-) mice had reduced atherosclerosis compared with
      the wild-type-LDLR(-/-) control mice. However, no significant difference was
      detected in EC-ARKO-LDLR(-/-) and SMC-ARKO-LDLR(-/-) mice compared with wild-type
      LDLR(-/-) mice, suggesting that the AR in monocytes/macrophages, and not in ECs
      and SMCs, plays a major role to promote atherosclerosis. Molecular mechanism
      dissection suggested that AR in monocytes/macrophages upregulated the tumor
      necrosis factor-alpha, integrin beta2, and lectin-type oxidized LDL receptor 1
      molecules that are involved in 3 major inflammation-related processes in
      atherosclerosis, including monocytes/macrophages migration and adhesion to human
      umbilical vein ECs, and subsequent foam cell formation. Targeting AR via the AR
      degradation enhancer, ASC-J9, in wild-type-LDLR(-/-) mice showed similar effects
      as seen in monocyte/macrophage ARKO-LDLR(-/-) mice with little influence on lipid
      profile. In conclusion, the AR in monocytes/macrophages plays key roles in
      atherosclerosis and targeting AR with ASC-J9 may represent a new potential
      therapeutic approach to battle atherosclerosis. 

PMID- 24688121
TI  - Strategy for standardization of preeclampsia research study design.
AB  - Preeclampsia remains a major problem worldwide for mothers and babies. Despite
      intensive study, we have not been able to improve the management or early
      recognition of preeclampsia. At least part of this is because of failure to
      standardize the approach to studying this complex syndrome. It is possible that
      within the syndrome there may be different phenotypes with pathogenic pathways
      that differ between the subtypes. The capacity to recognize and to exploit
      different subtypes is of obvious importance for prediction, prevention, and
      treatment. We present a strategy for research to study preeclampsia, which will
      allow discrimination of such possible subtypes and also allow comparison and
      perhaps combinations of findings in different studies by standardized data and
      biosample collection. To make studies relevant to current clinical practice, the
      definition of preeclampsia can be that currently used and accepted. However, more
      importantly, sufficient data should be collected to allow other diagnostic
      criteria to be used and applied retrospectively. To that end, we present what we
      consider to be the minimum requirements for a data set in a study of preeclampsia
      that will facilitate comparisons. We also present a comprehensive or optimal data
      set for in-depth investigation of pathophysiology. As we approach the definition
      of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to
      standardized protocols will hasten our understanding of the causes of
      preeclampsia and development of targeted treatment strategies. 

PMID- 24688122
TI  - Day-by-day blood pressure variability: cause or consequence of vascular brain
      injury?

PMID- 24688123
TI  - Connective tissue growth factor inhibition attenuates left ventricular remodeling
      and dysfunction in pressure overload-induced heart failure.
AB  - Connective tissue growth factor (CTGF) is involved in the pathogenesis of various
      fibrotic disorders. However, its role in the heart is not clear. To investigate
      the role of CTGF in regulating the development of cardiac fibrosis and heart
      failure, we subjected mice to thoracic aortic constriction (TAC) or angiotensin
      II infusion, and antagonized the function of CTGF with CTGF monoclonal antibody
      (mAb). After 8 weeks of TAC, mice treated with CTGF mAb had significantly better
      preserved left ventricular (LV) systolic function and reduced LV dilatation
      compared with mice treated with control immunoglobulin G. CTGF mAb-treated mice
      exhibited significantly smaller cardiomyocyte cross-sectional area and reduced
      expression of hypertrophic marker genes. CTGF mAb treatment reduced the TAC
      induced production of collagen 1 but did not significantly attenuate TAC-induced
      accumulation of interstitial fibrosis. Analysis of genes regulating extracellular
      matrix proteolysis showed decreased expression of plasminogen activator inhibitor
      1 and matrix metalloproteinase-2 in mice treated with CTGF mAb. In contrast to
      TAC, antagonizing the function of CTGF had no effect on LV dysfunction or LV
      hypertrophy in mice subjected to 4-week angiotensin II infusion. Further analysis
      showed that angiotensin II-induced expression of hypertrophic marker genes or
      collagens was not affected by treatment with CTGF mAb. In conclusion, CTGF mAb
      protects from adverse LV remodeling and LV dysfunction in hearts subjected to
      pressure overload by TAC. Antagonizing the function of CTGF may offer protection
      from cardiac end-organ damage in patients with hypertension. 

PMID- 24688124
TI  - Understanding the power of perinatal events and metabolic status in childhood.

PMID- 24688125
TI  - Associations of birth weight and postnatal weight gain with cardiometabolic risk
      parameters at 5 years of age.
AB  - The present prospective study assessed the impact of birth weight (BW) and
      postnatal weight gain on blood pressure and metabolic profile during the first 5
      years of life. One hundred thirty-nine newborns (63 women) born at term after
      uncomplicated pregnancies and in the absence of perinatal illness were included.
      Subjects were divided according to size at birth in small, appropriate, and large
      for gestational age. After the initial evaluation on the second day of life,
      infants were followed up at 6 months and 2 and 5 years. Anthropometric parameters
      and blood pressure were measured at each visit and metabolic assessment was
      performed at 5 years of age. Among the BW groups, mothers did not differ in terms
      of age, smoking, and weight gain during pregnancy. BW was a positive determinant
      of systolic blood pressure at birth. Afterward, current weight was the strongest
      determinant, becoming significant at 2 years of age and progressively increasing
      in influence. At 5 years insulin, the homeostasis model assessment index and
      triglycerides were dependent on BW, current weight, and postnatal weight gain. In
      addition, BW was positively associated with high-density lipoprotein-cholesterol
      and inversely so to uric acid. A positive relationship among insulin, blood
      pressure values, and uric acid was observed even early in life. In conclusion,
      the acceleration of early infant weight gain may aggravate the effects of low BW.
      Multiple interactions between hemodynamic and metabolic parameters foreshadow the
      clustering of cardiometabolic risk factors later in life. 

PMID- 24688126
TI  - Specific respiratory neuron types have increased excitability that drive
      presympathetic neurones in neurogenic hypertension.
AB  - A major aspect of hypertension is excessive sympathetic activity but the reasons
      for this remain elusive. Sympathetic tone is increased in the spontaneously
      hypertensive (SH) rat reflecting, in part, enhanced respiratory-sympathetic
      coupling. We aimed to identify which respiratory cells might have altered
      properties. Using the working heart-brain stem preparation, we monitored
      simultaneously sympathetic and respiratory nerve activity in combination with
      intracellular recordings of physiologically characterized medullary
      presympathetic or respiratory neurons. In SH rats, respiratory modulation of both
      inspiratory and postinspiratory phases of sympathetic activity was larger
      relative to Wistar rats. An additional burst of sympathetic activity in the
      preinspiratory phase was also present in SH rats. After synaptic isolation of
      rostral medullary presympathetic neurons, there was no difference in their
      excitability compared with neurons in Wistar rats. Rather, both pre-Botzinger
      preinspiratory and Botzinger postinspiratory neurons had increased neuronal
      excitability in SH rats relative to Wistar rats; this was attributed to higher
      input resistance/reduced leak current in preinspiratory neurons and reduced
      calcium activated potassium conductance in postinspiratory neurons. Thus, the
      respiratory network of the SH rat is reconfigured to a pattern dominated by
      heightened excitability of preinspiratory and postinspiratory neurons. These
      neurons both provide augmented excitatory synaptic drive to rostral medullary
      presympathetic neurons contributing to excessive sympathetic nerve activity
      associated with hypertension in the in situ SH rat. Our data indicate selective
      modulation of potassium conductances in 2 subsets of respiratory neurons
      contributing to neurogenic hypertension. 

PMID- 24688128
TI  - Day-to-day variability in home blood pressure is associated with cognitive
      decline: the Ohasama study.
AB  - Although an association between high blood pressure and cognitive decline has
      been reported, no studies have investigated the association between home blood
      pressure and cognitive decline. Home blood pressure measurements can also provide
      day-to-day blood pressure variability calculated as the within-participant SD.
      The objectives of this prospective study were to clarify whether home blood
      pressure has a stronger predictive power for cognitive decline than conventional
      blood pressure and to compare the predictive power of the averaged home blood
      pressure with day-to-day home blood pressure variability for cognitive decline.
      Of 485 participants (mean age, 63 years) who did not have cognitive decline
      (defined as Mini-Mental State Examination score, <24) initially, 46 developed
      cognitive decline after a median follow-up of 7.8 years. Each 1-SD increase in
      the home systolic blood pressure value showed a significant association with
      cognitive decline (odds ratio, 1.48; P=0.03). However, conventional systolic
      blood pressure was not significantly associated with cognitive decline (odds
      ratio, 1.24; P=0.2). The day-to-day variability in systolic blood pressure was
      significantly associated with cognitive decline after including home systolic
      blood pressure in the same model (odds ratio, 1.51; P=0.02), whereas the odds
      ratio of home systolic blood pressure remained positive, but it was not
      significant. Home blood pressure measurements can be useful for predicting future
      cognitive decline because they can provide information not only on blood pressure
      values but also on day-to-day blood pressure variability. 

PMID- 24688129
TI  - Backyard laying hens--a comment.

PMID- 24688130
TI  - Fixing peer review.

PMID- 24688127
TI  - Functional neural-bone marrow pathways: implications in hypertension and
      cardiovascular disease.

PMID- 24688131
TI  - An ethicist's commentary on industry research.

PMID- 24688132
TI  - Effects of xylazine, romifidine, or detomidine on hematology, biochemistry, and
      splenic thickness in healthy horses.
AB  - Alpha-2 agonist-induced changes in packed cell volume (PCV), total solids (TS),
      selected biochemical parameters, and splenic thickness were investigated in
      horses. Four healthy mares were treated in a blinded, randomized, cross-over
      design with a dose of xylazine (0.5 mg/kg), romifidine (0.04 mg/kg), or
      detomidine (0.01 mg/kg) IV, and detomidine (0.02 mg/kg) IM. Hematology, TS,
      colloid osmotic pressure (COP), plasma osmolality; glucose, lactate, urea (BUN)
      and electrolyte concentrations; venous blood pH and ultrasonographic splenic
      thickness were evaluated at intervals for 300 min. Repeated measures analysis of
      variance (ANOVA) were performed with P < 0.05. There was a significant change
      over time in PCV and TS following each treatment (P < 0.001), with median (range)
      reductions of 20.9% (12.9% to 27.3%) and 5.8% (3.0% to 10.3%), respectively. Red
      blood cell count, BUN, and COP decreased while osmolality, glucose, Na(+), and
      splenic thickness increased. Treatments induced clinically significant transient
      changes in PCV, TS, and other biochemical parameters, which should be considered
      when assessing horses that received these drugs. 

PMID- 24688133
TI  - Antimicrobial susceptibility of Escherichia coli F4, Pasteurella multocida, and
      Streptococcus suis isolates from a diagnostic veterinary laboratory and
      recommendations for a surveillance system.
AB  - Antimicrobial susceptibility data on Escherichia coli F4, Pasteurella multocida,
      and Streptococcus suis isolates from Ontario swine (January 1998 to October 2010)
      were acquired from a comprehensive diagnostic veterinary laboratory in Ontario,
      Canada. In relation to the possible development of a surveillance system for
      antimicrobial resistance, data were assessed for ease of management,
      completeness, consistency, and applicability for temporal and spatial statistical
      analyses. Limited farm location data precluded spatial analyses and missing
      demographic data limited their use as predictors within multivariable statistical
      models. Changes in the standard panel of antimicrobials used for susceptibility
      testing reduced the number of antimicrobials available for temporal analyses.
      Data consistency and quality could improve over time in this and similar
      diagnostic laboratory settings by encouraging complete reporting with sample
      submission and by modifying database systems to limit free-text data entry. These
      changes could make more statistical methods available for disease surveillance
      and cluster detection. 

PMID- 24688134
TI  - Retrospective risk factor assessment for complication following tibial tuberosity
      transposition in 137 canine stifles with medial patellar luxation.
AB  - This study identified risk factors for complication following tibial tuberosity
      transposition by retrospective examination of cases that used various surgical
      techniques. Records and radiographs of 113 dogs with 137 stifles undergoing
      tibial tuberosity transposition for medial patellar luxation were reviewed.
      Patient-specific factors, surgical factors, and complication information were
      recorded. Owners were contacted as necessary to attain a minimum of 30 days
      follow-up. Of 137 stifles, 59 (43%) had complications, with 24 (18%) identified
      as major complications. Factors significantly associated with reduced risk of
      complication included increased age [odds ratio (OR) 0.8] and concurrent cranial
      cruciate ligament rupture (OR 0.3). Factors significantly associated with
      increased risk of complication included large breed compared to toy breed (OR
      5.5), increased weight (OR 1.3), and use of a screw for tibial tuberosity
      fixation (OR infinity). While significant, these associations do not imply
      causality and prospective study is necessary to determine the ideal fixation
      method for individual patients. 

PMID- 24688135
TI  - Long-term outcome of permanent tracheostomies in dogs: 21 cases (2000-2012).
AB  - This retrospective study reports long-term outcome, survival, and complications
      in dogs which received a permanent tracheostomy due to upper airway obstruction.
      Data were collected from medical records (n = 21) in 2 institutions over a 12
      year period. Patients were followed until death, complications, causes of death,
      and survival times are reported. Major complications were reported in 50% of
      patients with 20% of patients receiving revision surgery. The most common
      complications were aspiration pneumonia and need for revision surgery. Median
      survival time was 328 days with 25% of patients surviving 1321 days or longer.
      Some (26%) patients died acutely at home at various times after surgery.
      Permanent tracheostomy is a viable procedure for patients with end stage upper
      airway obstruction; however, a subpopulation of patients suffers acute death at
      various times after surgery, which is thought to be due to airway obstruction. 

PMID- 24688136
TI  - Diurnal variations of central corneal thickness and intraocular pressure in dogs
      from 8:00 am to 8:00 pm.
AB  - Diurnal variations in central corneal thickness (CCT) and intraocular pressure
      (IOP) and their relationships were studied in healthy dogs. Central corneal
      thickness was measured by ultrasonic pachymetry and IOP by applanation tonometry
      in 16 beagle dogs. Measurements were taken every 90 min over 12 h (08:00 am to
      08:00 pm). The mean CCT and IOP values obtained during the sampling period were
      545.6 +/- 21.7 MUm (range: 471 to 595 MUm) and 15 +/- 2.2 mmHg (range: 10 to 19
      mmHg), respectively. The CCT and IOP showed statistically significant decreases
      at 6:30 pm and 5:00 pm, respectively (P < 0.001). Central corneal thickness and
      IOP values were lower in the afternoon/evening than in the morning and were
      positively correlated. Both findings are important for the diagnostic
      interpretation of IOP values in dogs. 

PMID- 24688137
TI  - Epidermoid cyst of the ileum in a miniature dachshund dog.
AB  - A 13-year-old castrated male miniature dachshund dog was presented with chronic
      vomiting and diarrhea. Contrast radiography and surgical exploration revealed an
      ileal cyst, which was excised. A diagnosis of epidermoid cyst was made from a
      combination of the clinical findings and histological examination of the surgical
      specimen. 

PMID- 24688138
TI  - Epizootic hemorrhagic disease in a yak.
AB  - Epizootic hemorrhagic disease virus (EHDV) infection was diagnosed in a 3-year
      old yak. The yak had signs of intermittent tremors, dysphagia, oral ulcerative
      lesions, hemorrhagic enteritis, tachypnea, and thrombocytopenia. Postmortem
      diagnostics confirmed EHDV (serotype 2) using reverse-transcriptase polymerase
      chain reaction (RT-PCR). Gross and histopathological results were consistent with
      EHDV reported in other species. 

PMID- 24688139
TI  - Uncommon acute neurologic presentation of canine distemper in 4 adult dogs.
AB  - Four uncommon cases of canine distemper (CD) were diagnosed in vaccinated adult
      dogs. All dogs had acute onset of neurologic signs, including seizures, abnormal
      mentation, ataxia, and proprioceptive deficits. Polymerase chain reaction for CD
      virus was positive on cerebrospinal fluid in 2 cases. Due to rapid deterioration
      the dogs were euthanized and CD was confirmed by postmortem examination. 

PMID- 24688140
TI  - Neurotropic T-cell-rich B-cell lymphoma in a 14-year-old Morgan gelding.
AB  - A 14-year-old Morgan gelding was presented for progressive weakness and muscle
      atrophy. The horse was initially diagnosed with equine protozoal myelitis based
      on history, physical examination, and laboratory diagnostics. Despite therapy,
      the horse declined clinically and was euthanized. Necropsy revealed a rare form
      of neurotropic lymphoma, described in this report. 

PMID- 24688141
TI  - Functional metastatic parathyroid adenocarcinoma in a dog.
AB  - A 12-year-old dachshund dog was presented for persistent hypercalcemia and
      hyperparathyroidism despite bilateral parathyroidectomy. Magnetic resonance
      imaging of the head, neck, and cranial mediastinum identified an increased number
      of cranial mediastinal lymph nodes with heterogeneous signal intensity.
      Hypercalcemia and hyperparathyroidism resolved after surgery to remove multiple
      cranial mediastinal lymph nodes, one of which contained presumed metastatic
      parathyroid tissue. 

PMID- 24688142
TI  - Public policy and veterinary medicine.

PMID- 24688143
TI  - Ensuring quality communication when irreconcilable differences exert outside
      pressure on the practice.

PMID- 24688144
TI  - Effectiveness of bromocriptine monotherapy or combination treatment with
      clomiphene for infertility in women with galactorrhea and normal prolactin: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Among women with unexplained infertility, 28% to 55% of patients with
      galactorrhea are normoprolactinemic. Bromocriptine, a common treatment for
      infertile women with hyperprolactinemia, has been used in the treatment of
      unexplained subfertility in women with galactorrhea and normal prolactin;
      however, its effectiveness and safety profile have never been determined.
      OBJECTIVE: The aim of this study was to determine the relative effectiveness and
      safety profile of bromocriptine monotherapy or as an adjunct to clomiphene
      citrate in women with galactorrhea and normal prolactin levels. METHODS: We
      conducted a search of the Cochrane Subfertility Review Group specialized register
      of controlled trials (March 2010), CENTRAL (The Cochrane Library, Issue 3, 2010),
      MEDLINE (1950-March 2010), EMBASE (1980-March 2010), and the China Biological
      Medicine Database (inception to March 2010) for relevant randomized controlled
      trials (RCTs) using the following terms: controlled, randomized, blinded,
      clinical trials, humans, galactorrhea, prolactin, bromocriptine, infertility, and
      subfertility. Additionally, reference lists of identified articles were searched
      for relevant articles. RESULTS: Of the 8 studies identified, 5 were excluded
      after full-text review for the following reasons: lack of a placebo group (2);
      difference in cointerventions (1); difference in end points (1); and systematic
      review (1). Therefore, 3 RCTs were included in this review. Bromocriptine
      administered in combination with clomiphene was found to be associated with a
      higher accumulative pregnancy rate compared with clomiphene monotherapy (fixed
      odds ratio [OR], 5.33; 95% CI, 2.62-10.88), and a lower miscarriage rate (fixed
      OR, 0.20; 95% CI, 0.05-0.76). Only 1 trial reported live birth as an outcome, and
      multiple pregnancy rates were poorly reported. Patient-reported adverse effects
      were mentioned in the studies, but reports were often incomplete. CONCLUSIONS:
      This review suggests the effectiveness of bromocriptine with clomiphene for
      infertility in women with galactorrhea and normal prolactin levels. Further RCTs
      of adequate power and of high methodologic quality are required to confirm these
      findings.

PMID- 24688145
TI  - Glucagon-like peptide-1 receptor agonists versus insulin glargine for type 2
      diabetes mellitus: A systematic review and meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of
      hypoglycemic drugs, including exenatide, liraglutide, albiglutide, lixisenatide,
      and taspoglutide. Insulin glargine is a standard agent used to supplement basal
      insulin in type 2 diabetes mellitus (T2DM). OBJECTIVE: The aim of this study was
      to review the efficacy and safety profiles of GLP-1 receptor agonists versus
      insulin glargine in type 2 diabetic patients who have not achieved treatment
      goals with oral hypoglycemic agents. METHODS: The Cochrane Library, MEDLINE,
      EMBASE, Science Citation Index Expanded, and the database of ongoing trials were
      searched from inception through April 2010. Additional data were sought from
      relevant Web sites, the American Diabetes Association, reference lists of
      included trials and related (systematic) reviews, and industry. Randomized
      controlled trials (RCTs) were selected if they were >=3 months in duration,
      compared GLP-1 receptor agonists with insulin glargine in patients with T2DM, and
      included >=1 of the following outcomes: mortality, complications of T2DM,
      glycemie control, weight, lipids, blood pressure, adverse effects, and health
      related quality of life. Quasirandomized controlled trials were excluded. The
      quality of the eligible studies was assessed on the basis of the following
      aspects: randomization procedure, allocation concealment, blinding, incomplete
      outcome data (intent-to-treat [ITT] analysis), selective outcome reporting, and
      publication bias. RESULTS: A total of 410 citations were retrieved; 5 multicenter
      RCTs that met the inclusion criteria were identified. They were all open-label
      designs with an insulin glargine arm, predefined outcomes reported, and ITT
      analysis. One trial had an unclear randomization procedure and allocation
      concealment. Publication bias was not able to be determined. No data wete found
      with regard to mortality or diabetes-associated complications, and few data were
      found on quality of life. The results of the metaanalysis suggest that insulin
      glargine was significantly better in reducing the fasting blood glucose (mean
      difference [MD] [95% CI], 1.31 [1.04 to 1.58]; P < 0.001), but exhibits greater
      incidence of nocturnal hypoglycemia (risk ratio [RR] [95% CI], 0.40 [0.23 to
      0.71]; P = 0.002) and influenza (RR [95% CI], 0.56 [0.32 to 0.98]; P = 0.04). GLP
      1 receptor agonists are more conducive to reducing weight (MD [95% CI], -3.96 [
      5.14 to -2.77]; P < 0.001), postprandial blood glucose (after breakfast, P <
      0.001; after dinner, P < 0.001), and LDL-C (MD [95% CI], -0.18 [-0.28 to -0.08];
      P < 0.001), but have significantly more gastrointestinal adverse effects (eg,
      nausea/ vomiting, P < 0.001). There were no significant differences between GLP-1
      receptor agonists and insulin glargine in reducing glycosylated hemoglobin
      (HbA1c) levels (MD [95% CI], -0.03 [-0.13 to 0.08]) and the overall incidence of
      hypoglycemia (RR [95% CI], 0.69 [0.42 to 1.14]). CONCLUSIONS: Compared with
      insulin glargine, GLP-1 receptor agonists did not have a significant difference
      in regard to reducing HbA1c levels and they were significantly associated with
      decreased weight but increased gastrointestinal adverse events. It remains
      unclear whether GLP-1 receptor agonists influence mortality or diabetes
      associated complications in patients with T2DM. More trials with longer follow-up
      are needed to determine the exact long-term efficacy and safety profiles of this
      new class of hypoglycemic drugs.

PMID- 24688146
TI  - Effects of lorglumide on growth and invasion of human pancreatic cancer cell line
      Mia PaCa-2 in vitro through the cholecystokinin-cholecystokinin-1 receptor
      pathway.
AB  - BACKGROUND: Cholecystokinin (CCK) has been found to be a growth stimulant through
      its special receptor pathway, especially for gastrointestinal malignancies.
      Although the CCK-1 receptor has been shown to be highly expressed in resected
      human pancreatic cancer samples, its role is less clear. OBJECTIVE: The aim of
      this in vitro study was to investigate the CCK-1 receptor expression and the
      function of the CCK-CCK-1 receptor pathway in the human pancreatic adenocarcinoma
      cell line, Mia PaCa-2. METHODS: The expression of the CCK-1 receptor in Mia PaCa
      2 cells was detected by reverse-transcriptase polymerase chain reaction and flow
      cytometry. CCK-1 receptor agonist CCK-8S (the major transmitter form of CCK) and
      antagonist lorglumide were cultured respectively with Mia PaCa-2. Three groups
      were created for this study: CCK-8S group (Mia PaCa-2 cells treated with CCK-8S),
      lorglumide group (Mia PaCa-2 cells treated with lorglumide), and the control
      group (Mia PaCa-2 cells alone). Investigators were blinded to group designation.
      3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and flow
      cytometry were used to detect the cell growth, cell cycle, and apoptosis.
      Apoptosis index rate was measured by terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick-end labeling. Cell invasion ability was
      observed by invasion assay. Expression of matrix metalloproteinase-2 (MMP-2) was
      measured by Western blotting. RESULTS: Mia PaCa-2 cells were found to express the
      CCK-1 receptor. Compared with the control group (70.2% [1.5%]), CCK-8S was
      associated with significant mean (SD) cell proliferation (85.1% [1.7%]; P =
      0.039), and the ratio in the S stage of the cell cycle increased significantly
      (50.5% [1.7%] vs 42.2% [1.4%]; P = 0.021). CCK-8S was also associated with
      increased Mia PaCa-2 cell invasion ability (123.8 [1.7] vs 102.1 [5.8]; P = 0.005
      vs control). Compared with the control group, lorglumide was associated with
      significantly inhibited cell growth (52.1% [1.8%]; P = 0.002) and cell invasion
      (77.6% [1.2%]; P = 0.003). Lorglumide also induced G0/G1 cell cycle arrest and
      apoptosis (27.1% [3-5%] vs 3-7% [0.6%]; P = 0.003 vs control). The change of
      invasion ability appeared to be mediated by MMP-2 expression, which was
      upregulated by CCK-8S and downregulated by lorglumide. CONCLUSION: The findings
      of this in vitro study suggest that CCK may exert a trophic action on the Mia
      PaCa-2 cell line, while lorglumide inhibited the cell growth and invasion.

PMID- 24688147
TI  - Effects of ezetimibe on glucose metabolism in patients with type 2 diabetes: A 12
      week, open-label, uncontrolled, pilot study.
AB  - BACKGROUND: A potential effect of ezetimibe, a novel cholesterol-absorption
      inhibitor, on insulin resistance has been reported in an animal model. OBJECTIVE:
      The aim of this study was to evaluate the effects of ezetimibe on glucose
      metabolism in patients with type 2 diabetes mellitus (T2DM). METHODS: Between
      March and June 2008, outpatients with T2DM who were being treated at Yokohama
      Sakae Kyosai Hospital, Yokohama, Japan, were enrolled in this pilot study if they
      had not achieved the target lipid levels recommended by the Japan Atherosclerosis
      Society Guidelines despite diet and exercise or a statin therapy for >=3 months.
      At baseline and at 4 and 12 weeks after open-label treatment with ezetimibe 10
      mg/d, the levels of lipid parameters, fasting plasma glucose (FPG), glycosylated
      hemoglobin (HbA1c), and high-sensitivity C-reactive protein were measured.
      Adverse effects (AEs) were assessed at each study visit by patient interviews and
      laboratory testing. RESULTS: A total of 21 consecutive patients (10 men, 11
      women; mean [SD] age, 72 [9] years; weight, 63.4 [10.5] kg; body mass index, 25.5
      [3.2] kg/m(2)) were enrolled in this study. The mean (SD) level of LDL-C
      decreased significantly from 146 (31) to 114 (27) mg/dL (-21%; P < 0.001) after
      12 weeks of treatment with ezetimibe. The mean level of remnant-like particle
      cholesterol also decreased significantly from 6.5 (3.8) to 4.8 (2.2) mg/dL (-15%;
      P = 0.03). Treatment with ezetimibe was associated with a reduction in FPG level
      from 127 (31) to 119 (30) mg/dL (P = 0.02), and HbAlc from 6.3% (0.6%) to 6.1%
      (0.7%) (P = 0.003). No AEs were observed or reported during the study period.
      CONCLUSION: In this small, open-label, uncontrolled, pilot study, ezetimibe was
      associated with a significant decrease in lipid parameters and improvement in
      glucose metabolism in these patients with T2DM.

PMID- 24688148
TI  - Pharmacokinetics of depside salts from Salvia miltiorrhiza in healthy Chinese
      volunteers: A randomized, open-label, single-dose study.
AB  - BACKGROUND: Depside salts from Salvia miltiorrhiza, with active components of
      lithospermic acid B (LSB), rosmarinic acid (RA), and lithospermic acid (LA), are
      a multicomponent drug marketed in China for the treatment of coronary heart
      disease. OBJECTIVES: The aims of this study were to determine the concentrations
      of LSB, RA, and LA in human plasma and urine, and to compare the pharmacokinetic
      properties of depside salts from S miltiorrhiza in healthy Chinese volunteers.
      METHODS: A randomized, open-label, single-dose study was conducted in healthy
      Chinese volunteers. Participants were randomly assigned to receive a single
      intravenous infusion of 100 or 200 mg of depside salts from S miltiorrhiza. Blood
      was collected through a venous cannula prior to study drug administration (0 min)
      and at 10, 20, 30, 60, 65, 70, 80, and 90 minutes and 2, 3, 4, 6, 8, 12, and 24
      hours after study drug administration. Urine samples were taken before study drug
      administration (0) and at 0 to 12 and 12 to 24 hours after study drug
      administration. LSB, RA, and LA concentrations in serum and urine were analyzed
      by an LC-MS/MS method. Tolerability was determined by clinical assessment; vital
      signs (ie, blood pressure, heart rate, breathing rate, body temperature)
      monitoring at baseline and at the end of the study, clinical laboratory tests
      (ie, hematology, blood biochemistry, hepatic function, renal function,
      urinalysis), 12-lead ECG measurements, and physical examinations at baseline and
      after completion of the study. RESULTS: Twelve Chinese volunteers (6 males, 6
      females; mean [SD] age, 25.2 [3.8] years; mean height, 165.7 [8.9] cm; mean body
      mass index, 21.6 [2.5] kg/m(2)) were enrolled in the study. Peak plasma
      concentrations of LSB, RA and LA were observed at 0.3 to 1 hour following the 1
      hour intravenous infusion, with respective mean (SD) Cmax of 4925 (1861), 174
      (61), and 361 (101) ng/mL for the 100-mg dose and 10,285 (2259), 308 (77), and
      674 (85) ng/mL for the 200-mg dose. The AUClast values for LSB, RA, and LA were
      4537 (1265), 129 (28), and 1229 (330) ng/mL/h, respectively, for the 100-mg dose
      and 10,426 (2589), 260 (53), and 2792 (729) ng/mL/h for the 200-mg dose. No
      significant difference in pharmacokinetic parameters was observed between male
      and female subjects. Three metabolites were found in the plasma with low
      concentrations. The urinary excretion recoveries of LSB, RA, and LA were 0.58%
      (0.42%), 25.21% (20.61%), and 10.02% (7.72%) for the 100-mg dose and 0.38%
      (0.18%), 20.11% (10.50%), and 6.34% (3.20%) for the 200-mg dose. No adverse
      events were reported by the subjects or found by the investigators in the
      analysis of vital signs, 12-lead ECG measurements, physical examinations, or
      clinical laboratory tests. CONCLUSIONS: Following single intravenous infusion of
      100 or 200 mg of depside salts from S miltiorrhiza to healthy Chinese subjects,
      no statistical differences in pharmacokinetic parameters were observed between
      males and females. The 2 doses of depside salts from S miltiorrhiza were
      clinically well tolerated during the study.

PMID- 24688149
TI  - Fesoterodine for overactive bladder: A review of the literature.
AB  - BACKGROUND: Overactive bladder (OAB) is a chronic condition affecting both men
      and women, with prevalence increasing with age. Antimuscarinics form the
      cornerstone of treatment of OAB. Fesoterodine, a nonselective muscarinic-receptor
      antagonist, was approved by the US Food and Drug Administration in late 2008 for
      once daily, oral administration in the treatment of OAB to relieve the symptoms
      of urinary urge incontinence, urgency, and frequency. OBJECTIVE: The aim of this
      review was to provide an overview of the mechanism of action of and clinical
      trial data for fesoterodine, and to discuss the present status of fesoterodine in
      the management of OAB. METHODS: The MEDLINE and Google Scholar databases were
      searched (June 1, 1999-December 1, 2009) using the terms fesoterodine, overactive
      bladder, and muscarinic antagonists. Full-text articles in English were selected
      for reference, and articles presenting the mechanism of action, pharmacokinetics,
      and data from clinical trials were included. The parameters measured were
      tolerability, efficacy, and health-related quality of life (HRQoL). Trials
      involving animals and Phase I studies were excluded. RESULTS: The initial
      literature search yielded 48 papers. A total of 20 articles fulfilled the
      inclusion criteria. In two 12-week, randomized, multicenter, Phase III clinical
      trials involving patients with increased micturition frequency and urgency and/or
      urinary urge incontinence (n = 836 and 1132 in each trial), both fesoterodine 4
      and 8 mg were associated with significantly improved symptoms of OAB (frequency
      of micturition, urgency, and urge incontinence) compared with placebo (P < 0.05).
      In a post hoc analysis of pooled data of the Phase III trials, HRQoL improved
      significantly with both doses. In a 12-week, Phase Illb trial, fesoterodine 4 and
      8 mg led to treatment satisfaction in ~80% of patients (of 516 enrolled) who were
      initially unsatisfied with their previous treatment. CONCLUSION: A review of the
      literature suggests that fesoterodine is an efficacious and well-tolerated
      treatment option for patients with OAB.

PMID- 24688150
TI  - Comparison of the effects of ketamine or lidocaine on fentanyl-induced cough in
      patients undergoing surgery: A prospective, double-blind, randomized, placebo
      controlled study.
AB  - BACKGROUND: Fentanyl-induced cough is common but has not been viewed as a serious
      anesthetic problem. However, the cough may be explosive at times, may require
      immediate intervention, and may be associated with undesirable increases in
      intracranial, intraocular, and intra-abdominal pressures. Prevention of
      fentanylinduced cough in such situations is of paramount importance. Ketamine, at
      concentrations achieved with standard clinical doses, has a direct relaxant
      effect on airway smooth muscle. OBJECTIVE: This study was designed to assess the
      effects of ketamine or lidocaine on fentanyl-induced cough. METHODS: This double
      blind, randomized, placebo-controlled study was conducted at the Erciyes
      University Medical School, Kayseri, Turkey. Consecutive adult patients aged 18 to
      65 years and classified as American Society of Anesthesiologists physical status
      I or II who were undergoing elective surgery with general anesthesia were
      enrolled. Patients were randomly allocated equally into 3 groups to receive
      lidocaine 1 mg/kg, ketamine 0.5 MUg/kg, or placebo intravenously 1 minute before
      fentanyl administration. Following intravenous fentanyl (1.5 MUg/kg over 2
      seconds) injection, an observer, unaware of the type of medication given to the
      patients, recorded the number of episodes of coughing, if any. Any episode of
      cough was classified as coughing and graded by investigators blinded to treatment
      as mild (1-2 coughs), moderate (3-4), or severe (>=5). Blood pressure, heart
      rate, pulse oximetry oxygen saturation (SpO2), and adverse effects (AEs) were
      recorded. RESULTS: A total of 368 patients were approached for inclusion; 300
      patients met the inclusion criteria and were enrolled in the study. No patients
      in the ketamine group had cough. The frequency of cough was significantly lower
      in the lidocaine (11/100 [11%]; P = 0.024) and ketamine (0/100; P = 0.001) groups
      compared with the placebo group (23/100 [23%]). The intensity of cough was
      significantly lower in the lidocaine (mild, 7/100 [7%]; moderate, 4/100 [4%]; P =
      0.037) and ketamine (0/100; P < 0.001) groups compared with the placebo group
      (mild, 10/100 [10%]; moderate, 12/100 [12%]; severe, 1/100 [1%]). Severe cough
      (>=5) was observed in 1 patient in the placebo group. Incidence and intensity of
      cough were significantly decreased in the ketamine group compared with the
      lidocaine group (incidence, P = 0.001; intensity, P = 0.003). There were no
      significant differences between groups with respect to systolic blood pressure,
      diastolic blood pressure, heart rate, SpO2, and AEs. CONCLUSION: Intravenous
      ketamine (0.5 mg/kg) significantly reduced the reflex cough induced by fentanyl
      compared with lidocaine and placebo, and was well tolerated.

PMID- 24688151
TI  - Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled
      epidural analgesia after subtotal gastrectomy: A prospective, randomized, double
      blind, controlled trial.
AB  - BACKGROUND: Nausea and vomiting are frequent adverse effects of patient
      controlled epidural analgesia (PCEA) with opioids. OBJECTIVE: This study was
      designed to assess the antiemetic effect of midazolam added to fentanyl
      ropivacaine PCEA. METHODS: In a prospective, randomized, double-blind, controlled
      trial, smoking patients with gastric cancer undergoing elective subtotal
      gastrectomy were evenly allocated to 1 of 2 treatment groups to manage
      postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 MUg/mL and midazolam
      0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 MUg/mL (control
      group). The PCEA infusion was set to deliver 4 MUL/h of the study solution, with
      a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of
      postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage
      of rescue analgesia and rescue antiemetic, respiratory depression, urinary
      retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after
      surgery. Total infused volume of PCEA at 72 hours after surgery was measured.
      RESULTS: A total of 60 patients were approached and randomized to treatment. No
      patients were excluded by exclusion criteria and all enrolled patients completed
      this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was
      significantly lower than in the control group. The overall frequency of PONV in
      the test group was significantly less than that of the control group (7% vs 40%;
      P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group
      was significantly lower than that in the control group (392.3 [68.9] vs 351.2
      [49.8] mL; P = 0.01). However, there were no significant differences in pain
      intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus
      between groups. No patient reported moderate or severe sedation, respiratory
      depression, or hypoxemia. In addition, there were no severe adverse events.
      CONCLUSIONS: Midazolam added to fentanyl-ropivacaine PCEA was associated with a
      significant reduction in the incidence of PONV compared with fentanyl-ropivacaine
      alone, and a significant decrease in the amount of PCEA administered without a
      significant increase in adverse events in these patients who underwent subtotal
      gastrectomy.

PMID- 24688152
TI  - Effects of vitamin C and melatonin on cysteamine-induced duodenal ulcer in a
      cholestatic rat model: A controlled experimental study.
AB  - BACKGROUND: Superoxide dismutase (SOD) is one of the defense mechanisms against
      free radicals. Cysteamine is a cytotoxic agent, acting through generation of
      reactive oxygen species (ROS) such as hydrogen peroxide, hydroxyl radical, and
      superoxide, and may decrease defense activity of SOD against ROS and induce
      duodenal ulcer. Melatonin is a suicidal antioxidant that has a protective effect
      against ROS and cytoprotective effect through inhibition of the decrease in SOD
      activity. OBJECTIVES: The primary aim of this study was to assess the effects of
      pretreatment with vitamin C and melatonin on cysteamine-induced duodenal ulcer.
      Secondary aims were to compare the ulcerogenic effect of cysteamine and the
      antiulcer effects of vitamin C and melatonin. METHODS: This study was performed
      in male Wistar rats (200-250 g) in 3 groups of equal size (n = 24): bile duct
      ligation-induced cholestasis (test), sham, and control groups. In the test and
      sham groups, laparotomy was performed under general anesthesia and the common
      bile duct was identified; in sham rats, the common bile duct was left in situ,
      but in test rats, the common bile duct was isolated and doubly ligated to induce
      cholestasis. Animals in each group were also divided into 4 equal subgroups (n =
      6). These subgroups were treated with vitamin C plus cysteamine, melatonin plus
      cysteamine, cysteamine alone, and saline, respectively. All animals were
      euthanized via overdose of ether anesthesia 24 hours after the last injection of
      cysteamine or saline, and 0.5 mL of blood was collected from the heart ventricle.
      The duodenum was cut open, washed with saline, fixed, and prepared for
      calculation of ulcer index (Szabo method) and histopathologic assessment. SOD
      activity was measured using a branded enzyme kit. RESULTS: In all 3 groups,
      animals treated with cysteamine had significantly increased mean (SE) ulcer index
      (test, 4.00 [0.10] vs 1.17 [0.30]; sham, 3.83 [0.16] vs 0.50 [0.22]; control,
      3.67 [0.21] vs 0 [0]) and decreased SOD activity (test, 146.41 [2.16] vs 299.83
      [1.94] U/mL; sham, 154.75 [2.02] vs 303.08 [0.35] U/mL; control, 157.08 [1.67] vs
      314.50 [1.14] U/mL) compared with saline-treated rats (all, P < 0.001). In the
      test rats, ulcer index was significantly increased and SOD activity was
      significantly decreased compared with the sham and control groups (both, P <
      0.001). Pretreatment with vitamin C and melatonin was associated with attenuation
      of ulcer index and increased SOD activity compared with rats treated with
      cysteamine alone (P < 0.001). There were no significant differences in ulcer
      index or SOD activity between groups administered vitamin C or melatonin.
      CONCLUSIONS: In this experimental study, pretreatment with melatonin or vitamin C
      in all rats produced significant attenuation of the ulcer index and enhanced SOD
      activity. Cysteamine-induced duodenal mucosal damage was greater in cholestatic
      rats compared with sham and control rats.

PMID- 24688153
TI  - Effect of Benincasa hispida fruits on testosterone-induced prostatic hypertrophy
      in albino rats.
AB  - BACKGROUND: Benincasa hispida Cogn. has been used traditionally in India for the
      management of urinary disorders. The fruit of B hispida is used as a diuretic and
      the seeds have been reported to possess antiangiogenic effects in prostate cells.
      OBJECTIVE: The aim of the present study was to examine the effect of petroleum
      ether extract, ethanolic extract, and B hispida seed oil on hyperplasia of the
      prostate induced by the subcutaneous administration of testosterone in rats.
      METHODS: In vitro studies were performed to determine the 5alpha-reductase
      inhibitory potential of the extracts. The results of those studies paved the way
      for the pharmacologic screening of the extracts to assess their potential against
      testosterone-induced hyperplasia in rats. Nine groups containing 10 rats per
      group were created for this study. Hyperplasia was induced by administration of
      testosterone (3 mg/kg SC) for 14 days in all the groups except the vehicle
      treated group. Simultaneous administration of petroleum ether extract (100 or 200
      mg/kg PO), ethanolic extract (100 or 200 mg/kg PO), and B hispida seed oil (20 or
      40 mg/kg PO) was conducted. A standard 5alpha-reductase inhibitor (ie,
      finasteride) was used as a positive control. The weight of the rats was recorded
      on day 0 (ie, day 1 of the study) and on day 14, and the influence of
      testosterone and test extracts on the weight of the rats was determined. On day
      14, rats were euthanized; prostates were dissected out, and weighed. The rats'
      prostate/body weight (P/BW) ratio was then determined. Histologic examinations
      were performed on prostates from each group. RESULTS: The petroleum ether extract
      as well as B hispida seed oil exhibited inhibition of 5alpha-reductase activity
      in in vitro studies. Ethanolic extract did not exhibit significant inhibitory
      potential in vitro. Further in vivo study found that testosterone treatment
      significantly increased the rats' P/BW ratio in all the groups except the vehicle
      treated rats, and this increase in weight was significantly inhibited in rats
      administered petroleum ether extract (100 and 200 mg/kg PO) and B hispida seed
      oil (20 and 40 mg/kg PO). Ethanolic extract did not exhibit any significant
      activity. CONCLUSIONS: Petroleum ether extract and B hispida seed oil inhibited
      testosterone-induced hyperplasia of the prostate in these rats. Further studies
      are needed to evaluate its effect in humans with benign prostatic hyperplasia.

PMID- 24688154
TI  - Effects of trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl
      diglycinate/niacinamide topical emulsion in Thai adults with melasma: a single
      center, randomized, double-blind, controlled study.
AB  - BACKGROUND: Melasma is an acquired hyperpigmentary disorder characterized by dark
      patches or macules located on the cheeks, forehead, upper lip, chin, and neck.
      Treatment of melasma involves the use of topical hypopigmenting agents such as
      hydroquinone, tretinoin, and azelaic acid and its derivatives. OBJECTIVE: The
      purpose of this study was to assess the efficacy of a formulation containing a
      combination of trans-4-(aminomethyl) cyclohexanecarboxylic acid/potassium azeloyl
      diglycinate/niacinamide compared with an emulsion-based control in the treatment
      of melasma in Thai adults. METHODS: In this single-center, randomized, double
      blind, controlled study, Thai patients with mild to moderate facial melasma
      (relative melanin value [RMV] in range of 20-120) were randomized for the
      application of either the test or the emulsion-based (control) product in the
      morning and before bedtime for 8 weeks. The supplemental sunscreen product with
      sun protection factor 30 was distributed to all patients. Subjects were assessed
      for the intensity of their hyperpigmented skin area by measuring the difference
      in the absolute melanin value between hyperpigmented skin and normal skin (RMV).
      This parameter was used as a primary outcome of this study. Additionally, the
      severity of melasma was determined visually using the Melasma Area and Severity
      Index (MASI) scored independently by 3 investigators. The assessments of melasma
      intensity and other skin properties were performed before administration (week 0)
      and every 2 weeks thereafter for up to 8 weeks. Other skin properties, including
      moisture content, pH, and redness (erythema value), were measured. Adverse events
      (AEs), including erythema, scaling, and edema, were also assessed by a
      dermatologist using the visual grading scale of Frosch and Kligman and COLIPA.
      RESULTS: The resulting primary intent-to-treat (ITT) population included 33
      patients in the test group and 34 patients in the control group. Sixty patients
      completed all 8 weeks of the study (on-treatment [OT] population): 91% (30) of
      the 33 patients in the test group, and 88% (30) of the 34 patients in the control
      group. Between-group differences in mean RMV were statistically significant at
      week 6 in both the primary ITT (P = 0.005) and OT (P = 0.006) populations. The
      significant differences in mean MASI scores between the test and the control
      groups were initially observed at weeks 4 (P = 0.005) and 8 (P = 0.027) in the OT
      and primary ITT populations, respectively. Other parameters, including skin pH,
      erythema, and moisture content did not significantly change from baseline at any
      time point of study. The incidence of AEs was not different between the test
      (4/33 [12%]) and control (5/34 [15%]) groups. CONCLUSIONS: The significant
      differences in RMVs between the test and control groups were observed after 6
      weeks of treatment, both in the primary ITT and OT populations. The incidence of
      patients with AEs was not significantly different between the test and control
      groups.

PMID- 24688155
TI  - Pharmacokinetic interaction between fluoxetine and omeprazole in healthy male
      volunteers: a prospective pilot study.
AB  - BACKGROUND: Fluoxetine is an inhibitor of the main metabolizing enzymes
      (cytochrome P450 [CYP] 2C19 and CYP3A4) of omeprazole and thus might influence
      that drug's pharmacokinetics. The changes in omeprazole's pharmacokinetics may
      have clinical significance concerning efficacy and tolerability of the treatment.
      OBJECTIVE: The aim of this study was to assess the pharmacokinetic interaction of
      fluoxetine with omeprazole in healthy volunteers. METHODS: The study enrolled
      healthy adult men and consisted of 2 periods. In the first period, all subjects
      received a single 40-mg dose of omeprazole. This was followed by an 8-day period
      during which fluoxetine monotherapy (60 mg/d) was administered as a single oral
      daily dose. At the end of those 8 days, the subjects were administered a 40-mg
      dose of omeprazole with a 60-mg dose of fluoxetine. Plasma concentrations of
      omeprazole were determined at 0.5, 1, 1.33, 1.66, 2, 2.5, 3, 4, 5, 6, 7, 8, 10,
      and 12 hour(s) after study drug administration. Omeprazole plasma concentrations
      were determined by a validated HPLC method. Pharmacokinetic parameters of omep
      razole were calculated using noncompartmental analysis. Adverse events were
      assessed throughout the study duration. RESULTS: Eighteen healthy male volunteers
      (mean [SD] age, 22.11 [2.52] years [range, 18-26 years]; body mass index, 23.34
      [2.31] kg/m(2) [range, 19.1-27.1 kg/m(2)]) were enrolled and completed the study.
      In the 2 periods of treatment, the mean Cmax of omeprazole was 730.8 ng/mL
      (omeprazole monotherapy) and 1725.5 ng/mL (combination treatment with
      fluoxetine). The observed AUC0-infinity was 1453.3 and 5072.5 ng/mL/h and AUC0-t
      was 1465.0 and 5185.3 ng/mL/h, respectively. The Tmax was 1.30 and 1.63 hours and
      the elimination rate constant was 0.753 and 0.482 hr(-1). The t1/2 was 0.96 and
      1.47 hours, whereas the mean residence time was 2.33 and 3.35 hours,
      respectively. Statistically significant differences were observed for all
      parameters between periods 1 and 2 (all, P < 0.001). CONCLUSION: The data found
      in this prospective pilot study suggest a pharmacokinetic interaction between
      fluoxetine and omeprazole in these healthy volunteers, but its relevance has to
      be confirmed.

PMID- 24688156
TI  - Effects of beta-glucan pretreatment on acetylsalicylic acid-induced gastric
      damage: An experimental study in rats.
AB  - BACKGROUND: NSAIDs have been found to induce gastrointestinal tract damage.
      Recently, it has been suggested that this might be mediated by lipid
      peroxidation. OBJECTIVE: The aim of this study was to assess the potential
      protective effects of beta-glucan against acetylsalicylic acid (ASA-induced
      gastric damage by means of its antioxidant capacity in an experimental rat model.
      METHODS: Thirty-two male Wistar albino rats (200-250 g) were randomized into 4
      groups consisting of 8 rats each. The beta-glucan group received 50 mg/kg beta
      glucan once a day for 10 days and 30 minutes before anesthesia. The ASA group
      received saline once a day for 10 days and 300 mg/kg (20 mg/mL) ASA as a single
      dose, 4 hours before anesthesia. The ASA+beta-glucan group was administered 50
      mg/kg beta-glucan once a day for 10 days and 30 minutes before anesthesia.
      Additionally, 300 mg/kg (20 mg/mL) ASA was administered as a single dose, 4 hours
      before anesthesia. The control group received saline once a day for 10 days and
      30 minutes before anesthesia. All medications were administered by intragastric
      gavage. The stomach from each rat was dissected and divided into 2 parts for
      histologic and biochemical analysis. Gastric tissue malondialdehyde (MDA), nitric
      oxide (NO) levels, catalase (CAT), superoxide dismutase (SOD), and glutathione
      peroxidase (GSH-Px) activities were determined for oxidative parameter analysis.
      RESULTS: The gastroprotective and antioxidant effects of beta-glucan appeared to
      attenuate the ASA-induced gastric tissue damage. Compared with the control group,
      MDA and NO levels and CAT and GSH-Px activities were significantly increased in
      the stomachs of ASA-treated rats (MDA, 4.12 [0.44] to 13.41 [1.05] MUmol/L; NO,
      8.04 [7.25-9.10] vs 30.35 [22.34-37.95] MUmol/g protein; CAT, 0.050 [0.004] to
      0.083 [0.003] k/g protein; GSH-Px, 0.57 [0.42-0.66] to 1.55 [1.19-1.76] U/L; all,
      P < 0.001), whereas SOD activity was significantly decreased in the same group
      (291 [29] to 124 [6] U/mL; P < 0.001). In the ASA+beta-glucan group, MDA and NO
      levels and CAT and GSH-Px activities were found to be significantly lower, while
      SOD activity was found to be significantly higher, in comparison with the ASA
      treated group (all, P < 0.001). CONCLUSION: beta-Glucan appeared to attenuate the
      gastric damage caused by ASA in these rats.

PMID- 24688157
TI  - Effects of griseofulvin on apoptosis through caspase-3- and caspase-9-dependent
      pathways in K562 leukemia cells: An in vitro study.
AB  - BACKGROUND: Griseofulvin, an oral nontoxic antifungal drug, has been reported to
      possess anticancer effect in human cancer cells, while the mechanisms are not
      completely understood. OBJECTIVE: The aim of this study was to investigate the
      cytotoxic effect of griseofulvin on K562 cells and to understand its underlying
      molecular pathways. METHODS: K562 cells were treated with griseofulvin at
      different concentrations for 24 hours, and the inhibition effect of griseofulvin
      on K562 cell proliferation was assessed by tetrazolium salt colorimetric assay.
      Apoptosis was assessed by examining nuclear morphology and quantifying
      phosphatidylserine externalization, and alterations in cellular morphology were
      analyzed by laser scanning confocal microscopy for fluorescent analysis. Flow
      cytometry was used in the analysis of cell cycle, mitochondrial membrane
      potential, and caspase pathways. RESULTS: Griseofulvin could inhibit the growth
      of K562 cells in a dose-dependent manner with a mean (SD) inhibitory
      concentration of 50% value of 15.38 (1.35) MUg/mL compared with untreated
      controls. Apoptosis was induced in K562 cells (38.35% [2.73%]; P < 0.01) by
      griseofulvin with the observation of both an increase in phosphatidylserine level
      and accumulation of chromatin nucleation in griseofulvintreated cells. In
      addition, cell-cycle analysis using propidium iodide staining suggested a
      significant G2/M accumulation (increase from mean 17.64% [4.49%] to 48.29
      [1.89%]; P < 0.01) as a result of griseofulvin treatment. Flow cytometry analysis
      found that griseofulvin treatment was associated with the depolarization of the
      mitochondrial membrane in K562 cells. Furthermore, increased activities of
      caspase-3 by 22.15-fold (P < 0.01) and caspase-9 by 16.73-fold (P < 0.01) were
      observed in K562 cells after griseofulvin treatment compared with the untreated
      control; a decrease of caspase-8 activity was also observed, but the change was
      not statistically significant. CONCLUSIONS: These findings suggest that
      griseofulvin inhibited growth of K562 cells and induced cell apoptosis through
      cell-cycle arrest and mitochondrial membrane potential decrease as well as
      caspase-3 and -9 activation. Further testing is needed to evaluate the potential
      of griseofulvin as a candidate in the chemotherapy of hematologic malignancies.

PMID- 24688158
TI  - Relationship between toll-like receptor 2 nonsynonymous single nucleotide
      polymorphisms and the effectiveness of Bacille Calmette-Guerin immunotherapy in
      preventing recurrence of superficial bladder cancer: A prospective study.
AB  - BACKGROUND: Intravesical Bacille Calmette-Guerin (BCG) immunotherapy has been
      used for several decades as a prophylactic approach against recurrence of
      superficial bladder cancer. However, its effectiveness has been both variable and
      unpredictable. Typically, cancer BCG-immunotherapy aims to redirect or modulate
      both innate and adaptive immune responses. The consequences of gene polymorphisms
      in several key immuno-regulatory molecules on the heterogeneity of the response
      to BCG-immunotherapy have been investigated. OBJECTIVE: The aim of this study was
      to evaluate the association of toll-like receptor (TLR) 2 polymorphisms (arginine
      to glutamine substitution at position 753 [Arg753Gln] and arginine to tryptophan
      substitution at position 677 [Arg677Trp]) and the outcome of BCG-immunotherapy.
      METHODS: This prospective study was conducted during a 3-year period from June
      2006 to July 2009. Consecutive patients were recruited during a 1-year period and
      followed for 2 years at the Department of Urology, Charles Nicolle Hospital,
      Tunis, Tunisia. Patients with superficial bladder tumors at stage Ta (noninvasive
      papillary carcinoma) or T1 (where the tumor has grown from the layer of cells
      lining the bladder into the connective tissue below but has not grown into the
      muscle layer of the bladder) of any grade were eligible; carcinoma in situ cases
      were excluded. The TLR2 Arg753Gln and Arg677Trp polymorphisms were studied in
      peripheral blood DNA from patients treated with BCG-immunotherapy after
      transurethral resection. RESULTS: A total of 112 consecutive patients were
      enrolled (101 men and 11 women; mean age, 63.9 years [range, 25-85 years]) and
      completed the 2-year followup. Polymerase chain reaction amplification followed
      by direct sequencing of the region containing the TLR2 single-nucleotide
      polymorphism (SNP) of interest did not detect Arg753Gln or Arg677Trp in any of
      the study participants belonging to either of 2 groups: responders (n = 67) and
      nonresponders (n = 45) to BCG-immunotherapy. CONCLUSIONS: No patients included in
      the study were found to have the 2 known TLR2 nonsynonymous SNPs, and the
      relative importance of these polymorphisms could not be definitely determined.
      However, a significant proportion of patients without these polymorphisms
      responded to BCG-immunotherapy, suggesting that these genetic variants are not
      critical in the effectiveness of this approach for preventing recurrence of the
      tumor.

PMID- 24688159
TI  - Tracheal compression during shoulder arthroscopy in the beach-chair position.
AB  - BACKGROUND: Respiratory distress is a rare complication of outpatient shoulder
      arthroscopy and mostly associated with general anesthesia, pneumothorax,
      anaphylaxis, or phrenic nerve paralysis. OBJECTIVE: We report on a shoulder
      arthroscopy complicated by tracheal compression caused by extravasation of
      irrigation fluid into soft tissues of the upper airway while the patient was in
      the beach-chair position under general anesthesia. CASE SUMMARY: A 33-year-old
      male was scheduled for shoulder arthroscopy for impingement syndrome of the right
      shoulder under general anesthesia combined with interscalene brachial plexus
      block. During the operation, the patient's neck, right chest, and shoulder were
      observed to be swollen and tense on palpation. A fiberoptic bronchoscopic
      evaluation through the endotracheal tube revealed that the trachea was compressed
      to the left, but not completely obstructed. It was determined that the irrigation
      fluid had leaked subcutaneously from the shoulder joint to the neck. Vital signs
      were stable and the patient could be adequately ventilated despite the airway
      obstruction. The patient was transferred to the ward 16 hours after the operation
      with stable vital signs and discharged from the hospital on the second day.
      CONCLUSIONS: We report a case of airway obstruction due to tracheal compression
      from extravasation of irrigation fluid during shoulder arthroscopy under general
      anesthesia combined with peripheral nerve block in the beach-chair position.
      General anesthesia with endotracheal intubation protected the patient from a
      possibly fatal complication.

PMID- 24688160
TI  - Letter to the editor.

PMID- 24688161
TI  - Annual author/subject indexes.

PMID- 24688162
TI  - Seeking Genomic Knowledge: The Case for Clinical Restraint.
AB  - Genome sequencing technology provides new and promising tests for clinical
      practice, including whole genome sequencing, which measures an individual's
      complete DNA sequence, and whole exome sequencing, which measures the DNA for all
      genes coding for proteins. These technologies make it possible to test for
      multiple genes in a single test, which increases the efficiency of genetic
      testing. However, they can also produce large amounts of information that cannot
      be interpreted or is of limited clinical utility. This additional information
      could be distracting for patients and clinicians, and contribute to unnecessary
      healthcare costs. The potential for genomic sequencing to improve care will be
      context-dependent, varying for different patients and clinical settings. This
      Article argues that a disciplined approach is needed, incorporating research to
      assess when and how genomic information can improve clinical outcomes, practice
      guidelines that direct optimal uses of genomic sequencing, and efforts to limit
      the production of genomic information unrelated to the clinical needs of the
      patient. Without this approach, genomic testing could add to current
      unsustainable healthcare costs and prove unaffordable in the long run.

PMID- 24688163
TI  - Targeted memory reactivation during slow wave sleep facilitates emotional memory
      consolidation.
AB  - STUDY OBJECTIVES: To investigate the mechanisms by which auditory targeted memory
      reactivation (TMR) during slow wave sleep (SWS) influences the consolidation of
      emotionally negative and neutral memories. DESIGN: Each of 72 (36 negative, 36
      neutral) picture-location associations were encoded with a semantically related
      sound. During a subsequent nap, half of the sounds were replayed in SWS, before
      picture-location recall was examined in a final test. SETTING: Manchester Sleep
      Laboratory, University of Manchester. PARTICIPANTS: 15 adults (3 male) mean age =
      20.40 (standard deviation +/- 3.07). INTERVENTIONS: TMR with auditory cues during
      SWS. MEASUREMENTS AND RESULTS: Performance was assessed by memory accuracy and
      recall response times (RTs). Data were analyzed with a 2 (sound: replayed/not
      replayed) * 2 (emotion: negative/neutral) repeated measures analysis of
      covariance with SWS duration, and then SWS spindles, as the mean-centered
      covariate. Both analyses revealed a significant three-way interaction for RTs but
      not memory accuracy. Critically, SWS duration and SWS spindles predicted faster
      memory judgments for negative, relative to neutral, picture locations that were
      cued with TMR. CONCLUSIONS: TMR initiates an enhanced consolidation process
      during subsequent SWS, wherein sleep spindles mediate the selective enhancement
      of reactivated emotional memories.

PMID- 24688164
TI  - Treatment of obstructive sleep apnea alters cancer-associated transcriptional
      signatures in circulating leukocytes.
AB  - RATIONALE: Obstructive sleep apnea (OSA) has been associated with a number of
      chronic disorders that may improve with effective therapy. However, the molecular
      pathways affected by continuous positive airway pressure (CPAP) treatment are
      largely unknown. We sought to assess the system-wide consequences of CPAP therapy
      by transcriptionally profiling peripheral blood leukocytes (PBLs). METHODS:
      Subjects in whom severe OSA was diagnosed were treated with CPAP, and whole
      genome expression measurement of PBLs was performed at baseline and following
      therapy. We used gene set enrichment analysis (GSEA) to identify pathways that
      were differentially enriched. Network analysis was then applied to highlight key
      drivers of processes influenced by CPAP. RESULTS: Eighteen subjects with
      significant OSA underwent CPAP therapy and microarray analysis of their PBLs.
      Treatment with CPAP improved apnea-hypopnea index (AHI), daytime sleepiness, and
      blood pressure, but did not affect anthropometric measures. GSEA revealed a
      number of enriched gene sets, many of which were involved in neoplastic processes
      and displayed downregulated expression patterns in response to CPAP. Network
      analysis identified several densely connected genes that are important modulators
      of cancer and tumor growth. CONCLUSIONS: Effective therapy of OSA with CPAP is
      associated with alterations in circulating leukocyte gene expression. Functional
      enrichment and network analyses highlighted transcriptional suppression in cancer
      related pathways, suggesting potentially novel mechanisms linking OSA with
      neoplastic signatures.

PMID- 24688165
TI  - High dosage of hypnotics predicts subsequent sleep-related breathing disorders
      and is associated with worse outcomes for depression.
AB  - OBJECTIVES: The rates of sleep related breathing disorders (SRBD) and treatment
      outcomes of depression were compared among insomnia patients who had stratified
      levels of hypnotic use during a 10-year follow-up (2001-2010). DESIGN: A
      nationwide population-based cohort study. SETTING: A nationally representative
      cohort of 1,000,000 enrollees. PARTICIPANTS: Data were collected from patients
      with major depressive disorder (MDD) and comorbid insomnia during January 2001 to
      December 2003 (study cohort N = 3,235). The mean dosage of hypnotics at baseline
      in the study cohort was calculated, and this information was used to categorize
      the cohort into three equal-sized groups based on levels of hypnotic dosage. MAIN
      OUTCOME MEASURES: Patient response to antidepressants during a period that
      extended from 1 year before to 1 year after the study (short-term outcome) and
      patient psychiatric and non-psychiatric visits and hospitalizations during follow
      up (long-term outcome) were analyzed. RESULTS: High-dosage patients presented the
      highest rates of subsequent SRBD diagnosis (3.9%), compared to medium-dosage
      patients (2.2%) and low-dosage patients (2.0%) (P = 0.011). Significantly more
      patients in the high-dosage group were difficult to treat with antidepressants
      compared to the other 2 groups (8.7% vs. 4.1% vs. 3.0%, P < 0.001), and their
      long-term depression outcome was worse for most parameters. Logistic regression
      showed that high-dosage hypnotics predicted the development of SRBD later (OR
      1.678 [CI, 1.051 to 2.680], P = 0.030). CONCLUSIONS: There is a reliable
      association between a history of high dosages of hypnotics, subsequent diagnosis
      of sleep related breathing disorder, and worse depression outcomes.

PMID- 24688166
TI  - Promise and challenge: the lens model as a biomarker for early diagnosis of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia pathologically
      characterized by cerebral amyloid-beta (Abeta) deposition. Early and accurate
      diagnosis of the disease still remains a big challenge. There is evidence that
      Abeta aggregation starts to occur years before symptoms arise. Noninvasive
      monitoring of Abeta plaques is critical for both the early diagnosis and
      prognosis of AD. Presently, there is a major effort on looking for a reasonably
      priced technology capable of diagnosing AD by detecting the presence of Abeta.
      Studies suggest that AD is systemic rather than brain-limited focus diseases and
      the aggregation of the disease-causing proteins also takes place in lens except
      the brain. There is a possible relationship between AD and a specific subtype of
      age-related cataract (supranuclear cataract). If similar abnormal protein
      deposits are present in the lens, it would facilitate non-invasive diagnosis and
      monitoring of disease progression. However, there are controversies on the issues
      related to performance and validation of Abeta deposition in lens as biomarkers
      for early detection of AD. Here we review the recent findings concerning Abeta
      deposition in the lenses of AD patients and evaluate if the ocular lens can
      provide a biomarker for AD. 

PMID- 24688167
TI  - Behavioral type-environment correlations in the field: a study of three-spined
      stickleback.
AB  - Behavioral type-environment correlations occur when specific behavioral types of
      individuals are more common in certain environments. Behavioral type-environment
      correlations can be generated by several different mechanisms that are probably
      very common such as niche construction and phenotypic plasticity. Moreover,
      behavioral type-environment correlations have important ecological and
      evolutionary implications. However, few studies have examined behavioral type
      environment correlations in natural populations. In this study, we asked whether
      some behavioral types of three-spined stickleback were more likely to occur in
      certain social environments (alone or in a shoal with other stickleback) or in
      certain microhabitats in a river (in the open or under cover). We found that
      individuals that were in shoals with other stickleback at the time of collection
      from the field emerged from a refuge more quickly compared to individuals that
      were found alone. In addition, fish that were alone in an open microhabitat
      explored more of a pool compared to fish that were alone in cover, but this
      difference did not occur among fish that were in shoals at the time of
      collection. Subsequent analyses of gut contents suggested that differences in
      microhabitat use were consistent over time. Our study provides some of the first
      evidence for behavioral type-environment correlations in a natural population of
      non-human animals.

PMID- 24688168
TI  - Comparison of levels and duration of detection of antibodies to bovine viral
      diarrhea virus 1, bovine viral diarrhea virus 2, bovine respiratory syncytial
      virus, bovine herpesvirus 1, and bovine parainfluenza virus 3 in calves fed
      maternal colostrum or a colostrum-replacement product.
AB  - Colostrum-replacement products are an alternative to provide passive immunity to
      neonatal calves; however, their ability to provide adequate levels of antibodies
      recognizing respiratory viruses has not been described. The objective of this
      study was to compare the serum levels of IgG at 2 d of age and the duration of
      detection of antibodies to bovine viral diarrhea virus 1 (BVDV-1), bovine viral
      diarrhea virus 2 (BVDV-2), bovine respiratory syncytial virus (BRSV), bovine
      herpesvirus 1 (BHV-1), and bovine parainfluenza virus 3 (BPIV-3) in calves fed
      maternal colostrum (MC) or a colostrum replacement (CR) at birth. Forty newborn
      male Holstein calves were assigned to the CR or the MC group. Group CR (n = 20)
      received 2 packets of colostrum replacement (100 g of IgG per 470-g packet),
      while group MC (n = 20) received 3.8 L of maternal colostrum. Blood samples for
      detection of IgG and virus antibodies were collected from each calf at birth, at
      2 and 7 d, and monthly until the calves became seronegative. Calves in the MC
      group had greater IgG concentrations at 2 d of age. The apparent efficiency of
      absorption of IgG was greater in the MC group than in the CR group, although the
      difference was not significant. Calves in the CR group had greater concentrations
      of BVDV neutralizing antibodies during the first 4 mo of life. The levels of
      antibodies to BRSV, BHV-1, and BPIV-3 were similar in the 2 groups. The mean time
      to seronegativity was similar for each virus in the 2 groups; however, greater
      variation was observed in the antibody levels and in the duration of detection of
      immunity in the MC group than in the CR group. Thus, the CR product provided
      calves with more uniform levels and duration of antibodies to common bovine
      respiratory viruses. 

PMID- 24688169
TI  - Effect of rider experience and evaluator expertise on subjective grading of
      lameness in sound and unsound sports horses under saddle.
AB  - The primary objective of this study was to investigate whether rider experience
      influences the assessment and grading of lameness in horses based on under-saddle
      gait analysis. Thirteen adult sports horses in active training were included in
      the study. After a baseline lameness and neurologic examination by the principal
      investigators, horses were videotaped while being ridden by an experienced and a
      less experienced rider. A 3-minute video was made for each horse and rider and 26
      videos were randomly ordered and compiled on a DVD. Veterinarians with different
      levels of experience in evaluating lameness and veterinary students viewed the
      DVD and assigned a lameness score to each horse/rider combination. In a model
      accounting for the expertise of the evaluator, there was no difference in overall
      lameness scores between experienced and less experienced riders. This result was
      consistent for both sound and unsound horses. The overall lameness scores
      reported by specialists and students, however, differed significantly. The
      lameness score reported by the study participants while the horse was ridden was
      significantly associated with the subjective baseline lameness assessment
      reported by the principal investigators for the same limb when the horse was not
      under saddle. Additional work is necessary to determine whether riders with even
      lower skill levels would further alter the balance and motion pattern of the
      horse and have more influence on subjective grading of lameness. 

PMID- 24688170
TI  - Acute exercise does not induce an acute phase response (APR) in Standardbred
      trotters.
AB  - The purpose of the study was to investigate whether acute strenuous exercise
      (1600- to 2500-m race) would elicit an acute phase response (APR) in Standardbred
      trotters. Blood levels of several inflammatory markers [serum amyloid A (SAA),
      haptoglobin, fibrinogen, white blood cell count (WBC), and iron], muscle enzymes
      [creatinine kinase (CK) and aspartate transaminase (AST)], and hemoglobin were
      assessed in 58 Standardbred trotters before and after racing. Hemoglobin levels
      increased and iron levels decreased 12 to 14 h after racing and haptoglobin
      concentrations, white blood cell counts, and iron levels were decreased 2 and/or
      7 d after racing. Concentrations of CK, AST, SAA, and fibrinogen were unaltered
      in response to racing. Acute strenuous exercise did not elicit an acute phase
      reaction. The observed acute increase in hemoglobin levels and decreases in
      haptoglobin and iron levels may have been caused by exercise-induced hemolysis,
      which indicates that horses might experience a condition similar to athlete's
      anemia in humans. The pathogenesis and clinical implications of the hematological
      and blood-biochemical changes elicited by acute exercise in Standardbred trotters
      in the present study warrant further investigation. 

PMID- 24688171
TI  - Recovery from desflurane anesthesia in horses with and without post-anesthetic
      xylazine.
AB  - The objective of this study was to compare recovery from desflurane anesthesia in
      horses with or without post-anesthetic xylazine. Six adult horses were
      anesthetized on 2 occasions, 14 d apart using a prospective, randomized crossover
      design. Horses were sedated with xylazine, induced to lateral recumbency with
      ketamine and diazepam, and anesthesia was maintained with desflurane. One of 2
      treatments was administered intravenously at the end of anesthesia: xylazine [0.2
      mg/kg body weight (BW)] or an equivalent volume of saline. Recovery parameters
      were recorded and assessed by 2 blinded observers. A Wilcoxon signed-rank test
      was used to analyze recovery data. Heart rate, arterial blood pressures, and
      arterial blood gas data were analyzed using 2-way analysis of variance (ANOVA)
      for repeated measures. Values of P < 0.05 were considered significant. Duration
      of anesthesia was not different between groups. Administration of xylazine at the
      end of desflurane anesthesia was associated with significantly longer times to
      first movement, endotracheal tube removal, first attempt to achieve sternal
      recumbency, sternal recumbency, first attempt to stand, and standing. Number of
      attempts to stand and quality of recovery scores were not different between
      groups. Administering xylazine after desflurane anesthesia resulted in longer
      recovery times. Recovery scores were not significantly different between groups. 

PMID- 24688172
TI  - [Bacterial biofilms: their importance in animal health and public health].
AB  - Bacterial biofilms are structured communities of bacterial cells enclosed in a
      self-produced polymer matrix that is attached to a surface. Biofilms protect and
      allow bacteria to survive and thrive in hostile environments. Bacteria within
      biofilms can withstand host immune responses, and are much less susceptible to
      antibiotics and disinfectants when compared to their planktonic counterparts. The
      ability to form biofilms is now considered an attribute of many microorganisms.
      Diseases associated with biofilms require novel methods for their prevention,
      diagnosis and treatment; this is largely due to the properties of biofilms.
      Furthermore, the presence of biofilms on surfaces found at farms, slaughterhouses
      or food processing plants will have an impact on the efficacy of disinfection
      protocols. Surprisingly, biofilm formation by bacterial pathogens of veterinary
      or zoonotic importance has received relatively little attention. The objective of
      this brief Review article is to bring awareness about the importance of biofilms
      to animal health stakeholders.(Translated by the authors). 

PMID- 24688174
TI  - Porcine salivary analysis by 2-dimensional gel electrophoresis in 3 models of
      acute stress: a pilot study.
AB  - The purpose of this research was to study changes in the salivary proteome of
      healthy pigs in stressful situations to identify any potential new salivary
      biomarker of stress. Three groups of animals were subjected to 3 stress models:
      snaring restraint followed by simulated sampling of vena cava blood; brief
      transport by road; and restriction of movement in a digestibility cage. Saliva
      was obtained from each animal before and 15 and 30 min after the induction of
      stress. The samples from the animals that showed the greatest increase in
      salivary cortisol concentration were pooled and run on 2-dimensional gels.
      Coomassie Brilliant Blue R-250 was used for spot detection and mass spectrometry
      for spot identification. Statistical analyses showed that 2 proteins had
      significant differences in expression before and after the induction of stress.
      These proteins were identified as odorant-binding protein and fragments of
      albumin. Further studies will be necessary to confirm the value of using these
      proteins as salivary biomarkers of stress in pigs. 

PMID- 24688173
TI  - Immunogenicity and efficacy of a recombinant adenovirus expressing hemagglutinin
      from the H5N1 subtype of swine influenza virus in mice.
AB  - The H5N1 influenza viruses infect a range of avian species and have recently been
      isolated from humans and pigs. In this study we generated a replication-defective
      recombinant adenovirus (rAd-H5HA-EGFP) expressing the hemagglutinin (HA) gene of
      H5N1 A/Swine/Fujian/1/2001 (SW/FJ/1/01) and evaluated its immunogenicity and
      protective efficacy in BALB/c mice. The recombinant virus induced high levels of
      hemagglutination inhibition (HI) antibody at a median tissue culture infective
      dose of 10(8) or 10(7). Compared with mice in the control groups, the mice
      vaccinated with rAd-H5HA-EGFP did not show apparent weight loss after challenge
      with either the homologous SW/FJ/1/01 or the heterologous H5N1
      A/Chicken/Hunan/77/2005 (CK/HuN/77/05). Replication of the challenge virus was
      partially or completely inhibited, and viruses were detected at significantly
      lower numbers in the organs of the vaccinated mice, all of which survived the
      challenge with CK/HuN/77/05, whereas most of the control mice did not. These
      results indicate that rAd-H5HA-EGFP can provide effective immune protection from
      highly pathogenic H5N1 viruses in mice and is therefore a promising new candidate
      vaccine against H5N1 influenza in animals. 

PMID- 24688175
TI  - Specific contrast ultrasound using sterically stabilized microbubbles for early
      diagnosis of thromboembolic disease in a rabbit model.
AB  - Specific contrast ultrasound is widely applied in diagnostic procedures on humans
      but remains underused in veterinary medicine. The objective of this study was to
      evaluate the use of microbubble-based contrast for rapid ultrasonographic
      diagnosis of thrombosis in small animals, using male New Zealand white rabbits
      (average weight about 3.5 kg) as a model. It was hypothesized that the use of
      microbubble-based contrast agents will result in a faster and more precise
      diagnosis in our model of thrombosis. A pro-coagulant environment had been
      previously established by combining endothelial denudation and external vessel
      wall damage. Visualization of thrombi was achieved by application of contrast
      microbubbles [sterically stabilized, phospholipid-based microbubbles filled with
      sulfur hexafluoride (SF6) gas] and ultrasonography. As a result, rapid and clear
      diagnosis of thrombi in aorta abdominalis was achieved within 10 to 30 s (mean:
      17.3 s) by applying microbubbles as an ultrasound contrast medium. In the control
      group, diagnosis was not possible or took 90 to 180 s. Therefore, sterically
      stabilized microbubbles were found to be a suitable contrast agent for the rapid
      diagnosis of thrombi in an experimental model in rabbits. This contrast agent
      could be of practical importance in small animal practice for rapid diagnosis of
      thrombosis.

PMID- 24688176
TI  - Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus
      (FeLV) in shelter cats on the island of Newfoundland, Canada.
AB  - Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are
      retroviruses found within domestic and wild cat populations. These viruses cause
      severe illnesses that eventually lead to death. Housing cats communally for long
      periods of time makes shelters at high risk for virus transmission among cats. We
      tested 548 cats from 5 different sites across the island of Newfoundland for FIV
      and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV,
      respectively. Two sites had significantly higher seroprevalence of FeLV infection
      than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope
      gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2
      sequences were most closely related to FeLV subtype-B and endogenous feline
      leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences
      at different sites demonstrate that some shelters are at greater risk of FeLV
      infections and recombination can occur at sites of high seroprevalence. 

PMID- 24688177
TI  - Antimicrobial susceptibility of Streptococcus suis isolated from clinically
      healthy swine in Brazil.
AB  - Streptococcus suis is an important pathogen in the swine industry. This study is
      the first to report on the antimicrobial susceptibility of S. suis isolated from
      clinically healthy pigs in Brazil; the fourth major pork producer in the world.
      The antimicrobial susceptibility of 260 strains was determined by disc diffusion
      method. Strains were commonly susceptible to ceftiofur, cephalexin,
      chloramphenicol, and florfenicol, with more than 80% of the strains being
      susceptible to these antimicrobials. A high frequency of resistance to some of
      the antimicrobial agents was demonstrated, with resistance being most common to
      sulfa-trimethoprim (100%), tetracycline (97.69%), clindamycin (84.61%),
      norfloxacin (76.92%), and ciprofloxacin (61.15%). A high percentage of multidrug
      resistant strains (99.61%) were also found. The results of this study indicate
      that ceftiofur, cephalexin, and florfenicol are the antimicrobials of choice for
      empirical control of the infections caused by S. suis. 

PMID- 24688178
TI  - Evaluation of a real-time polymerase chain reaction assay of the outer membrane
      protein P2 gene for the detection of Haemophilus parasuis in clinical samples.
AB  - A real-time polymerase chain reaction (PCR) assay of the outer membrane protein
      (OMP) P2 gene was developed and used to test 97 putative Haemophilus parasuis
      pure cultures and 175 clinical tissue samples. With standard culture isolation as
      the gold standard, the diagnostic sensitivity and specificity of the PCR assay
      were determined to be 83% and 80%, respectively. 

PMID- 24688179
TI  - Effect of native Lactobacillus murinus LbP2 administration on total fecal IgA in
      healthy dogs.
AB  - The objective of the present work was to determine the effect of Lactobacillus
      murinus strain LbP2 on canine fecal immunoglobulin A (IgA) levels. Seven dogs
      were orally treated with a 3-mL suspension of L. murinus LbP2 containing 5 *
      10(9) colony-forming units on alternate days for 2 wk. Six dogs were treated with
      3 mL of phosphate-buffered saline as placebo. Fecal samples were taken from the
      rectal ampulla on days 0 and 16, and the total canine fecal IgA concentration was
      determined with an immunoperoxidase assay kit. The IgA levels of individual dogs
      were compared with the nonparametric Wilcoxon test. Differences were considered
      significant when the P-value was less than 0.05. An increase in the total fecal
      IgA concentration was observed in the 7 dogs after treatment with L. murinus LbP2
      (P = 0.01796). No differences were detected between the initial total fecal IgA
      values and those obtained at the end of placebo treatment. Thus, after oral
      administration L. murinus LbP2 showed potential immunomodulatory effects, an
      important property to assess in a microorganism being considered for use as a
      probiotic. 

PMID- 24688181
TI  - Validation of Rules of TwoTM as a paradigm for assessing asthma control.
AB  - Assessing asthma control at each patient encounter is an essential task to
      determine pharmacologic requirements. Rules of Two (Ro2) was created from the
      original 1991 National Asthma Education Program guidelines to determine the need
      for controller therapy. This study determined the degree of agreement between Ro2
      and the Expert Panel Report (EPR-3) definition of "in control" asthma and
      compared that value with the Asthma Control Test (ACT) in a group of asthmatics
      for the purpose of validating this tool. Patients with documented asthma were
      randomized to complete Ro2 or ACT prior to being assessed for asthma control by
      certified asthma educators using an EPR-3 template. Assessments occurred in
      either a specialty asthma clinic or at a local health fair. Patients were also
      queried for their personal assessment of asthma control. The primary statistical
      methodology employed was the degree of agreement (kappa) between each survey tool
      and the EPR-3 template. Of 150 patients, 72% did not have their asthma in
      control, based on the EPR-3 template. Ro2 identified 58% of patients not in
      control of their asthma, whereas ACT identified 36%, with kappa scores of 0.41
      for Ro2 and 0.37 for ACT compared with the EPR-3 template. These were not
      significantly different. Of the 150 patients, 75% considered their asthma in
      control based on self-assessments, with a kappa of 0.23. In 14 of 73 ACT
      questionnaires, scores were not added or were misadded. Eliminating evaluation of
      static lung function significantly improved both kappa scores of Ro2 and ACT. In
      conclusion, Ro2 identifies patients with uncontrolled asthma as well as ACT and
      may be useful to the primary assessing clinician in determining asthma control. 

PMID- 24688180
TI  - Ex vivo evaluation of 7 polydioxanone for closure of equine ventral midline
      celiotomies.
AB  - The objective of this study was to compare the bursting strength (BS) and mode of
      failure (MF) of ventral midline (VM) celiotomies closed with USP 7 polydioxanone
      (7PD) in 1 or 2 simple continuous sections. A bursting strength model, consisting
      of inserting and inflating a 200-L polyurethane bladder through a 25-cm VM
      celiotomy, was used on 15 fresh equine cadavers. Celiotomies were closed using
      7PD in 2 separate sections (4 knots), 2 continuous sections (3 knots), or a
      single section (2 knots) using a simple continuous pattern. The horses'
      signalment, body weight, number of total knots, MF, and BS were recorded and
      analyzed statistically for interactions. No difference was found between the BS
      of VM celiotomies closure types (P = 0.4). All celiotomy/ suture constructs
      failed at the abdominal wall. The celiotomy closure types evaluated in this study
      provided a secure method of closure in VM celiotomies in vivo. 

PMID- 24688182
TI  - Impact of a surveillance screening program on rates of methicillin-resistant
      Staphylococcus aureus infections with a comparison of surgical versus nonsurgical
      patients.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of
      health care-associated infection. The overall effectiveness of surveillance
      screening programs is not well established. A retrospective cohort study was
      performed to evaluate the impact of a surveillance screening program on the rates
      of health care-associated MRSA infection (HA-MRSA-I) at a single institution. A
      subset of surgical patients was analyzed separately. Multivariate regression
      techniques were used to identify predictors of the desired outcomes. The overall
      MRSA infection rate was 1.3% in the before cohort and 3.2% in the after cohort.
      After excluding patients with a history of MRSA infection or MRSA colonization,
      HA-MRSA-I decreased from 1.2% to 0.87%. There was a similar overall increase in
      the surgical group, 1.4% to 2.3%, and decrease in HA-MRSA-I, 1.4% to 1.0% (P <
      0.001). For all patients, surgery, African American race, and increased length of
      stay conferred an increased likelihood of HA-MRSA-I. Females and patients in the
      after cohort had a lower risk of HA-MRSA-I (P < 0.01). In the after cohort, the
      results were similar, with surgery, African American race, and length of stay
      associated with an increased risk, and female sex associated with a decreased
      risk (P < 0.05). African American race and increased age had a higher likelihood
      of screening positive for MRSA colonization, while the surgical group, females,
      and Hispanic patients were less likely (P < 0.05). HA-MRSA-I was associated with
      a higher mortality among all patients (P < 0.001). Mortality rates were similar
      with HA-MRSA-I for all patients (10.8% vs 9.5%, P = 0.55) and in the surgical
      group (8.3% vs 6.8%, P = 0.58). In conclusion, surveillance programs may be
      effective in decreasing HA-MRSA-I. Further studies are needed to determine how to
      reduce transmission, particularly among African Americans and those with
      increased lengths of stay. 

PMID- 24688183
TI  - Improving hospital staff compliance with environmental cleaning behavior.
AB  - Reducing the incidence of healthcare-associated infections requires proper
      environmental cleanliness of frequently touched objects within the hospital
      environment. An intervention was launched in June 2012 and repeated in February
      2013 and August 2013 to increase hospital room cleanliness with repeated
      education and training of nursing and environmental services staff to reduce
      healthcare-associated infections at Cook Children's Medical Center. Random rooms
      were tested, staff were trained about proper cleaning, rooms were retested for
      surface cleanliness, and preintervention and postintervention values were
      compared. The percentage of cleaned surfaces improved incrementally between the
      three trials-with values of 20%, 49%, and 82% showing that repeat training
      favorably changed behavior in the staff (P = 0.007). During the study period,
      during which other infection control interventions were also introduced, there
      was a decline from 0.27 to 0.21 per 1000 patient days for Clostridium difficile
      infection, 0.43 to 0.21 per 1000 patient days for ventilator-associated
      infections, 1.8% to 1.2% for surgical site infections, and 1.2 to 0.7 per 1000
      central venous line days for central line-associated bloodstream infections. 

PMID- 24688184
TI  - Ethnic disparities in the prevalence of the metabolic syndrome in American
      adults: data from the Examination of National Health and Nutrition Examination
      Survey 1999-2010.
AB  - Data from the National Health and Nutrition Examination Survey were stratified by
      weight, gender, and ethnicity for six survey years from 1999 to 2010 for
      variables that satisfy the criteria for metabolic syndrome (MS). Results showed
      that 34% of the US adult population had MS. No significant gender disparities in
      MS prevalence were found. Black men had a significantly lower prevalence of MS
      than Black women and White men from 1999 to 2008 (P < 0.05). Women had a 60%
      higher abdominal adiposity than men in the US population (P = 0.00048; pregnant
      females were excluded). Although there seem to be ethnic differences in the
      prevalence of MS, the expression of MS is not a sufficient risk to culminate in
      cardiovascular disease; rather, nutritional, genetic, and environmental factors
      are necessary to finalize its expression into overt disease. 

PMID- 24688185
TI  - A cohort analysis of the cardiovascular risk factors in the employees of a
      pediatric hospital from 2009 to 2012.
AB  - A retrospective longitudinal cohort regression analysis was completed in 853 of
      the 3435 employees of Cook Children's Hospital who participated all 4 years (2009
      to 2012) in an employer wellness program. The presence of the metabolic syndrome
      (MS) was used as an outcome measure for the success of the wellness program. Data
      were stratified by weight, gender, and ethnicity. The odds ratios and regression
      analysis showed a significant decline in MS over the 4 years of the study (P =
      0.008), as well as a significant association between MS and obesity and
      overweight status (P < 0.0001), male gender (P = 0.0018), and all ethnic
      categories (P < 0.05) except African American ethnicity and the multiple
      ethnicity category. Age was strongly associated with risk for MS. Overall, the
      study showed that the wellness program significantly decreased the incidence of
      MS (P < 0.05). 

PMID- 24688186
TI  - Factors affecting adherence to a quality improvement checklist on an inpatient
      hepatology service.
AB  - Given the increasing emphasis on measuring quality indicators such as adherence
      to practice guidelines, we sought to determine the factors and address the
      barriers affecting guideline adherence on an academic inpatient hepatology
      service. We performed a single-center, prospective observational study.
      Physicians were given a handheld checklist to complete daily. We first measured
      the adherence rate and studied factors affecting adherence by performing surveys.
      We then modified the program to address the factors affecting adherence and
      reassessed the adherence rate. There was a baseline 46% checklist adherence rate.
      Reasons given for nonadherence fell into two categories: ease of task and
      physician commitment from both attending physicians and housestaff. Specific
      reasons given were that the attending did not prompt (39%), the adherence sheet
      was not in the chart (35%), the individual forgot (12%), as well as lack of time,
      unclear protocol, "too difficult," and "didn-t pay attention" (4% each). Each of
      these factors was addressed with a multimodal approach. Thereafter, the adherence
      rate rose from 46% to 83% (P < 0.001). Maintaining checklist adherence is time
      intensive and requires commitment from the whole medical team. 

PMID- 24688187
TI  - Characteristics of Native Americans with HIV and implications for care.
AB  - Limited data have been published about HIV infections and response to
      antiretroviral therapy in the Native American population. We reviewed baseline
      characteristics of 112 Native American patients to determine if there were any
      shared characteristics that would dictate the best treatment for this population.
      Metabolic diseases and psychiatric disorders were common findings among our
      patients. Native American patients should be monitored and screened as
      appropriate for comorbid conditions, and these disease states should be
      considered when choosing an antiretroviral regimen. 

PMID- 24688188
TI  - Comparison of the frequency and level of serum total cholesterol >300 mg/dL in
      patients at the same Texas hospital in a single month in 1993 and in 2013.
AB  - The clinical pathology laboratory database of a large tertiary hospital in
      Dallas, Texas, was searched for patients having a serum total cholesterol > 300
      mg in a single month in 1993 and in 2013. In September 1993, 63 patients had a
      serum total cholesterol > 300 mg/dL (range 302-1515 [mean 431, median 349]), and
      in September 2013, 12 patients had serum total cholesterol levels > 300 mg/dL
      (range 303-442 [mean 334, median 316.5]), an 81% decline in the numbers of
      patients and a 23% decline in the average total cholesterol levels during the 20
      year period. 

PMID- 24688189
TI  - Opsoclonus myoclonus syndrome: an unusual presentation for West Nile virus
      encephalitis.
AB  - A record number of West Nile virus (WNV) cases and fatalities seen in 2012 have
      brought to light the numerous manifestations of neuroinvasive disease. We report
      a case of opsoclonus myoclonus syndrome attributed to WNV and its clinical course
      after treatment with a combination of steroids and intravenous immunoglobulin.
      Our objective is to highlight opsoclonus myoclonus syndrome as a potential
      manifestation of WNV encephalitis. 

PMID- 24688191
TI  - Bilateral diaphragmatic paralysis associated with the use of the tumor necrosis
      factor-alpha inhibitor adalimumab.
AB  - A 51-year-old woman was referred for evaluation of progressive dyspnea of 3
      months- duration. She had received 3 doses of adalimumab for treatment of
      rheumatoid arthritis prior to the onset of her dyspnea. Her chest examination
      revealed absent diaphragmatic movement with inspiration. Spirometry showed a
      severe restrictive defect. Radiologic studies confirmed the diagnosis of
      bilateral diaphragmatic paralysis. Laboratory and radiologic workup excluded
      other possible causes of the diagnosis. Adalimumab was discontinued, and she was
      treated with bilevel positive airway pressure ventilation and intravenous
      immunoglobulin. Three months later, the diaphragmatic paralysis persisted. This
      is the second reported case of bilateral diaphragmatic paralysis occurring in a
      patient who had received adalimumab. Acute neuropathies are rare side effects of
      tumor necrosis factor-alpha inhibitors. 

PMID- 24688190
TI  - Fatal Clostridium septicum infection in a patient with a hematological
      malignancy.
AB  - A 49-year-old woman with acute myeloid transformation of myelodysplastic syndrome
      was admitted with mild erythema and pain in the right thigh and left forearm. She
      was doing well and had been discharged the previous day after consolidation
      chemotherapy. Examination showed only mild erythema and tenderness of the right
      thigh. She was started on broad-spectrum antibiotics. Discoloration progressed
      rapidly, and within hours the right femoral and left brachial pulses were not
      palpable. She was taken to the operating room for a suspicion of embolic arterial
      occlusion. Surgical incision, however, revealed extensive necrosis of the tissues
      with the presence of gas. Her relatives did not want her to undergo amputation.
      The patient developed refractory hypotension and died within 15 hours of
      presentation. Blood samples later tested positive for Clostridium septicum. This
      case is presented to create awareness about the subtle presentation and rapid
      progression of this infection, which can lead to death in less than 24 hours. 

PMID- 24688192
TI  - Celiac artery disease and fatal rupture of a hepatic artery aneurysm in the
      Ehlers-Danlos syndrome.
AB  - Isolated visceral arteriopathies of the celiac and hepatic artery are rare. We
      present a case of a Caucasian man who presented with abdominal pain and was found
      to have a spontaneous celiac artery dissection. Genetic analysis revealed a
      mutation consistent with Ehlers-Danlos syndrome type IV. The patient died 2
      months later from a spontaneous rupture of his hepatic artery. 

PMID- 24688193
TI  - The most common cause of hemoptysis worldwide: a fluke?
AB  - Global travel is associated with an increasing incidence of helminthic infections
      in nonendemic regions. We describe a patient with recurrent hemoptysis from a
      chronic infection not commonly found in the USA. 

PMID- 24688194
TI  - Stress-induced (takotsubo) cardiomyopathy following thoracic epidural steroid
      injection for postherpetic neuralgia.
AB  - We present what may be the first documented case of takotsubo cardiomyopathy
      following a thoracic epidural steroid injection. The 77-year-old patient had many
      risk factors predisposing her to takotsubo cardiomyopathy, including gender,
      postmenopausal status, and numerous recent stressful events in her life. Although
      she presented to the emergency department with symptoms of an acute myocardial
      infarction, her findings on electrocardiography, echocardiography, coronary
      angiography, and cardiac enzymes supported the diagnosis of takotsubo
      cardiomyopathy. While takotsubo cardiomyopathy is rare, it is important for the
      clinician to distinguish it from an acute myocardial infarction, as the two
      conditions present similarly but may have distinctly different clinical outcomes.

PMID- 24688195
TI  - Takotsubo cardiomyopathy following epidural steroid injection: yet another way to
      break the heart.

PMID- 24688196
TI  - Irregular cardiac rhythm with wide QRS complexes.

PMID- 24688197
TI  - Inverted P waves, QRS complexes, and T waves in lead I in a 64-year-old woman.

PMID- 24688198
TI  - Triple-hit lymphoma.
AB  - We report a case of a triple-hit lymphoma in a 72-year-old man. This lymphoma was
      diagnosed using morphology, flow cytometry, immunochemistry, and cytogenetics.
      Since many triple-hit lymphomas have not been documented in the literature, it is
      important to bring attention to this entity, as this lymphoma has different
      prognostic and therapeutic implications than other diffuse large B-cell
      lymphomas, thus making a correct and early diagnosis important. 

PMID- 24688199
TI  - Small bowel intussusception causing a postoperative bowel obstruction following
      laparoscopic low anterior resection in an adult.
AB  - Adult intussusception usually presents with nonspecific symptoms such as
      abdominal pain, bloating, nausea, vomiting, and a change in bowel habits.
      Although postoperative intussusception has been described in the pediatric
      population, there has been little description of it in the adult population.
      Postoperative intussusception has unique challenges, as hydrostatic reduction may
      compromise bowel anastomoses. Surgery is the universal treatment in these
      patients. In adults, delay in diagnosis and definitive treatment may be a direct
      result of common symptomatology between postoperative ileus and intussusception.
      We present a case of an adult patient who underwent laparoscopic low anterior
      resection for rectal cancer and developed a small bowel intussusception causing
      obstruction requiring surgery. To our knowledge, this is the first report of a
      small bowel intussusception masquerading as a postoperative ileus in an adult.
      While most postoperative delayed bowel function is attributed to ileus, abscess
      formation, or anastomotic leak, other uncommon etiologies, including
      intussusception, may occur and are important to include in the differential
      diagnosis. 

PMID- 24688200
TI  - Fatal abdominal hemorrhage associated with gallbladder perforation due to large
      gallstones.
AB  - Gallbladder perforation is a relatively uncommon complication of acute
      cholecystitis and may occur with or without gallstones. Prophylactic
      cholecystectomy has been recommended for patients with very large stones (>3 cm)
      due to an increased risk of gallbladder cancer. We present the case of a 68-year
      old woman who died of hemorrhagic shock following gallbladder perforation due to
      very large gallstones. This case provides additional support for consideration of
      prophylactic cholecystectomy in patients with very large gallstones. 

PMID- 24688201
TI  - Methemoglobinemia precipitated by benzocaine used during intubation.
AB  - Methemoglobinemia is a rare cause of tissue hypoxia that can quickly become fatal
      without immediate recognition and prompt treatment. It refers to an increase in
      methemoglobin in the red blood cells, which can be due to genetic deficiency of
      the enzymes responsible for reducing hemoglobin or can develop after exposure to
      oxidizing agents or xenobiotics. Local anesthetics, particularly benzocaine, have
      long been implicated in the formation of methemoglobin. Benzocaine is used for
      teething pain as well as before invasive procedures such as intubation and
      transesophageal echocardiogram. In this case report, we describe a patient with
      acute appendicitis who developed severe methemoglobinemia following use of
      benzocaine during an emergent intubation. Our objective is to increase awareness
      of this rare but potentially fatal complication associated with the use of this
      anesthetic. 

PMID- 24688202
TI  - Where is that hemodialysis catheter (superior vena cava or aorta)? A case of
      intraarterial catheter placement.
AB  - We present a case of a previously unrecognized intraarterial placement of a
      central venous catheter (CVC)-in this case, a large-bore hemodialysis catheter in
      an 82-year-old woman. CVC insertions have become a common practice in hospitals
      due to a variety of indications, and tunneled CVCs still remain an important form
      of access in patients with end-stage renal disease. Intraarterial puncture is a
      common complication during CVC insertion, while intraarterial (mis)placement is
      fairly uncommon and if unrecognized can lead to significant morbidity and
      mortality. 

PMID- 24688203
TI  - Renal failure due to Capnocytophaga canimorsus generalized Shwartzman reaction
      from a dog bite (DF-2 nephropathy).
AB  - We report a case of a 54-year-old man who developed gram-negative sepsis with
      multiorgan failure and generalized Shwartzman reaction after sustaining a dog
      bite. The causative organism was the fastidious gram-negative rod Capnocytophaga
      canimorsus, which is a commensal organism found in the oral flora of dogs and
      cats. More than 30 years after it was first described and despite technological
      advances in identification techniques, proper identification of this organism
      remains a challenge. In light of the increase in pet ownership as well as the
      increase in the different immunocompromised populations of the 21st century, we
      decided to revisit the case and reignite awareness of physicians caring for
      patients with recent dog or cat bites presenting with fulminant sepsis. 

PMID- 24688204
TI  - Imaging manifestations of a dreaded obstetric complication in the immediate
      postpartum period.
AB  - HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome is a dreaded
      complication that may develop during pregnancy or in the immediate postpartum
      period. Rarely this syndrome manifests itself with imaging findings. We report a
      case of HELLP syndrome in which the diagnosis was reaffirmed via imaging
      findings. 

PMID- 24688205
TI  - Fetal demise due to cord entanglement in the early second trimester.
AB  - In this report, we describe a rare cause of in utero fetal death, a complex
      entanglement of the umbilical cord around the fetal neck. At the 16th gestational
      week of pregnancy, routine fetal ultrasonography showed no fetal heartbeat.
      Thereafter, the fetus was delivered vaginally in the breech presentation. The
      neck was found to be encircled by multiple tight loops of the umbilical cord.
      Other than a thin and elongated neck, there were no dysmorphic features and no
      chromosomal abnormality on cytogenetic analysis. 

PMID- 24688206
TI  - Ingrown toenails (unguis incarnatus): Nail braces/bracing treatment.
AB  - Nail bracing is a safe, simple, and inexpensive treatment option that avoids
      surgery, requires no anesthetic, requires no recovery period, allows wearing the
      existing shoes, offers immediate relief from pain, and allows the practice of
      daily activities. Braces can be used for prolonged periods of times. If
      recurrence occurs, reapplication of bracing is usually required. 

PMID- 24688207
TI  - Tributes to George J. Race, MD, PhD.

PMID- 24688208
TI  - Cardiologist in the shadow of Angkor Wat: A medical mission to Cambodia.
AB  - In a medical mission to Cambodia, our team of doctors, dentists, and nurses saw
      over 1000 patients during 4 days of clinics. The most common cardiovascular
      problems were hypertension (11%) and heart murmurs (3%). Obesity and a history of
      diabetes were very rare. Unlike the cardiac patients I typically see in my
      Atlanta office, the Cambodians were trim and muscular from their predominantly
      farming and, less often, construction jobs. They are a gentle, seemingly happy
      people, appreciative of whatever limited medical help we could offer.
      Tuberculosis was the most prevalent serious illness noted. 

PMID- 24688209
TI  - A tale of Congress, continuing medical education, and the history of medicine.
AB  - Well-intentioned attempts by the Senate Finance Committee to improve the content
      and quality of continuing medical education (CME) offerings had the unanticipated
      consequence of decimating academically oriented history of medicine conferences.
      New guidelines intended to keep CME courses free of commercial bias from the
      pharmaceutical industry were worded in a fashion that caused CME officials at
      academic institutions to be reluctant to offer CME credit for history of medicine
      gatherings. At the 2013 annual conference of the American Association for the
      History of Medicine, we offered a novel solution for determining CME credit in
      line with current guidelines. We asked attendees to provide narrative critiques
      for each presentation for which they desired CME credit. In this essay, we
      evaluate the efficacy of this approach. 

PMID- 24688210
TI  - Mentoring: A tale of two poems, filling graveyards, and learning the art of
      medicine.
AB  - Polar approaches to mentoring are reflected in this pair of poems, which on first
      inspection appear to be unrelated. Mentoring comes in different forms, and
      combining medicine, mentoring, and poetry in one essay is an opportunity to
      explore the vital role mentoring plays in medical education. A nod toward the
      humanistic side of medicine is also illuminated by the selected poetry and
      associated discussion. 

PMID- 24688211
TI  - HIPAA: A flawed piece of legislation.

PMID- 24688212
TI  - Facts and ideas from anywhere.

PMID- 24688213
TI  - Scavenging rate constants of hydrophilic antioxidants against multiple reactive
      oxygen species.
AB  - Scavenging rate constants of eight hydrophilic antioxidants, including caffeic
      acid, chlorogenic acid, genistein, glutathione, N-acetylcysteine, rutin, trolox,
      and uric acid against multiple ROS, namely superoxide anion, hydroxyl radical,
      singlet oxygen, and alkoxyl radical were determined with the electron spin
      resonance method. Direct flash photolysis measurement of the second-order rate
      constant in the reaction of alkoxyl radical plus the spin trap 5,5-dimethyl
      pyrroline N-oxide made it possible to evaluate scavenging rate constants in
      antioxidants. The magnitudes of scavenging rate constants were notably dependent
      on the character of each ROS and the overall rate constants were highest in
      hydroxyl radical scavenging and the lowest in superoxide anion. The highest
      scavenging rate constant against superoxide anion was obtained by chlorogenic
      acid (2.9 * 10(5) M(-1) s(-1)) and the lowest was by N-acetylcysteine (5.0 *
      10(2) M(-1) s(-1)). For singlet oxygen, the highest was by glutathione (9.4 *
      10(8) M(-1) s(-1)) and the lowest was by uric acid (2.3 * 10(6) M(-1) s(-1)). All
      other numbers are listed and illustrated. Redox potential measurements of the
      antioxidants indicated that the antioxidants are likely to react with superoxide
      anion and singlet oxygen through electron transfer processes. 

PMID- 24688214
TI  - Scavenging of reactive oxygen species induced by hyperthermia in biological
      fluid.
AB  - The scavenging activity of rat plasma against hyperthermia-induced reactive
      oxygen species was tested. The glutathione-dependent reduction of a nitroxyl
      radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which was restricted by
      adding superoxide dismutase or by deoxygenating the reaction mixture, was applied
      to an index of superoxide (O2 (*-)) generation. A reaction mixture containing 0.1
      mM 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl and 1 mM glutathione was
      prepared using 100 mM phosphate buffer containing 0.05 mM
      diethylenetriaminepentaacetic acid. The reaction mixture was kept in a screw-top
      vial and incubated in a water bath at 37 or 44 degrees C. The time course of the
      electron paramagnetic resonance signal of 4-hydroxyl-2,2,6,6
      tetramethylpiperidine-N-oxyl in the reaction mixture was measured by an X-band
      EPR spectrometer (JEOL, Tokyo, Japan). When the same experiment was performed
      using rat plasma instead of 100 mM PB, the glutathione-dependent reduction of 4
      hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, i.e., generation of O2 (*-), was
      not obtained. Only the first-order decay reduction of 4-hydroxyl-2,2,6,6
      tetramethylpiperidine-N-oxyl, which indicates direct reduction of 4-hydroxyl
      2,2,6,6-tetramethylpiperidine-N-oxyl, was obtained in rat plasma. Adding 0.5%
      albumin to the phosphate buffer reaction mixture could almost completely inhibit
      O2 (*-) generation at 37 degrees C. However, addition of 0.5% albumin could not
      inhibit O2 (*-) generation at 44 degrees C, i.e., hyperthermic temperature.
      Ascorbic acid also showed inhibition of O2 (*-) generation by 0.01 mM at 37
      degrees C, but 0.02 mM or more could inhibit O2 (*-) generation at 44 degrees C.
      A higher concentration of ascorbic acid showed first-order reduction, i.e.,
      direct one-electron reduction, of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N
      oxyl. Hyperthermia-induced O2 (*-) generation in rat plasma can be mostly
      inhibited by albumin and ascorbic acid in the plasma. 

PMID- 24688215
TI  - Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid
      uptake in gastric epithelial cells.
AB  - Photodynamic therapy and photodynamic diagnosis using 5-aminolevulinic acid (ALA)
      are clinically useful for cancer treatments. Cancer cells have been reported that
      5-aminolevulinic acid is incorporated via peptide transporter 1, which is one of
      the membrane transport proteins, and has been reported to be significantly
      expressed in various gastrointestinal cancer cells such as Caco-2. However, the
      mechanism of this protein expression has not been elucidated. Concentration of
      reactive oxygen species (ROS) is higher in cancer cells in comparison with that
      of normal cells. We have previously reported that ROS derived from mitochondria
      is likely related to invasions and proliferations of cancer cells. Since 5
      aminolevulinic acid is the most important precursor of heme which is necessary
      protein for cellular proliferations, mitochondrial ROS (mitROS) may be also
      related to peptide transporter 1 expressions. In this study, we used a rat
      gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1, and we
      clarified the ALA uptake mechanism and its relations between mitROS and peptide
      transporter 1 expression in RGK1. We also used our self-established stable clone
      of cell which over-expresses manganese superoxide dismutase, a mitROS scavenger.
      We studied differences of the photodynamic therapy effects in these cells after
      ALA administrations to clear the influence of mitROS. 

PMID- 24688216
TI  - The astaxanthin-induced improvement in lipid metabolism during exercise is
      mediated by a PGC-1alpha increase in skeletal muscle.
AB  - Astaxanthin, a xanthophyll carotenoid, accelerates lipid utilization during
      aerobic exercise, although the underlying mechanism is unclear. The present study
      investigated the effect of astaxanthin intake on lipid metabolism associated with
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      in mice. Mice were divided into 4 groups: sedentary, sedentary and astaxanthin
      treated, exercised, and exercised and astaxanthin-treated. After 2 weeks of
      treatment, the exercise groups performed treadmill running at 25 m/min for 30
      min. Immediately after running, intermuscular pH was measured in hind limb
      muscles, and blood was collected for measurements. Proteins were extracted from
      the muscle samples and PGC-1alpha and its downstream proteins were measured by
      western blotting. Levels of plasma fatty acids were significantly decreased after
      exercise in the astaxanthin-fed mice compared with those fed a normal diet.
      Intermuscular pH was significantly decreased by exercise, and this decrease was
      inhibited by intake of astaxanthin. Levels of PGC-1alpha and its downstream
      proteins were significantly elevated in astaxanthin-fed mice compared with mice
      fed a normal diet. Astaxanthin intake resulted in a PGC-1alpha elevation in
      skeletal muscle, which can lead to acceleration of lipid utilization through
      activation of mitochondrial aerobic metabolism. 

PMID- 24688218
TI  - Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer
      cells and modifies intestinal polyp development in Apc (Min/+) mice.
AB  - Excessive prostaglandin production by cyclooxygenase-2 in stromal and epithelial
      cells is a causative factor of colorectal carcinogenesis. Thus, compounds which
      inhibit cyclooxygenase-2 transcriptional activity in colon epithelial cells could
      be candidates for anti-carcinogenic agents. A cyclooxygenase-2 transcriptional
      activity in the human colon cancer cell line DLD-1 has been measured using a beta
      galactosidase reporter gene system. Using this system, we demonstrated that the
      decrease in basal cyclooxygenase-2 transcriptional activities at 100 uM sesamol,
      one of the lignans in sesame seeds, was 50%. Other compounds in sesame seeds such
      as sesamin, sesamolin, ferulic acid, and syringic acid did not exhibit
      significant suppression of cyclooxygenase-2 transcriptional activity at up to 100
      uM. In a following experiment, 6-week-old male Min mice, Apc-deficient mice, were
      divided into a non-treated and 500 ppm sesamol groups. At the age of 15 weeks, it
      was found that treatment with sesamol decreased the number of polyps in the
      middle part of small intestine to 66.1% of the untreated value. Moreover, sesamol
      suppressed cyclooxygenase-2 and cytosolic prostaglandin E2 synthase mRNA in the
      polyp parts. The present findings may demonstrate the novel anti-carcinogenetic
      property of sesamol, and imply that agents that can suppress cyclooxygenase-2
      expression may be useful cancer chemopreventive agents. 

PMID- 24688217
TI  - Role of Nrf2 in the alteration of cholesterol and bile acid metabolism-related
      gene expression by dietary cholesterol in high fat-fed mice.
AB  - Nuclear factor-E2-related factor 2 (Nrf2) is a regulator of lipid metabolism as
      well as various cytoprotective enzymes and may be involved in the pathogenesis of
      non-alcoholic fatty liver disease. Although, bile acids affect lipid metabolism,
      the role of Nrf2 in bile acid metabolism remains unclear. In this study, it was
      tested how Nrf2 modulates lipid and bile acid homeostasis in liver in response to
      changes of cholesterol absorption under high-fat diet using Nrf2-null mice. Eight
      week-old male wild-type and Nrf2-null mice (n = 6/group) were divided into three
      groups fed the following diets: 1) control diet containing 4% soybean oil and 16%
      lard, 2) control diet plus ezetimibe, 3) control diet plus cholesterol. Blood and
      livers were removed after 4 weeks feeding. High cholesterol diet increased
      hepatic expression of liver X receptor alpha target genes related to fatty acid
      metabolism (FAS, ACC1, SREBP-1c, SCD-1c and CD36), cholesterol transport
      (Abcg5/abcg8) and bile acid synthesis (Cyp7a1) in wild type mice. However, these
      genes were not induced in Nrf2-null mice. These findings suggest that Nrf2 has a
      relation to liver X receptor alpha and controls the regulation of gene
      expressions related to lipid and bile acid metabolism. 

PMID- 24688219
TI  - Short-term dietary phosphate restriction up-regulates ileal fibroblast growth
      factor 15 gene expression in mice.
AB  - Members of the fibroblast growth factor (FGF) 19 subfamily, including FGF23,
      FGF15/19, and FGF21, have a role as endocrine factors which influence the
      metabolism of inorganic phosphate (Pi) and vitamin D, bile acid, and energy. It
      has been reported that dietary Pi regulates circulating FGF23. In this study, the
      short-term effects of dietary Pi restriction on the expression of FGF19 subfamily
      members in mice were analyzed. An initial analysis confirmed plasma FGF23 levels
      positively correlated with the amount of dietary Pi. On the other hand, ileal
      Fgf15 gene expression, but not hepatic Fgf21 gene expression, was up-regulated by
      dietary Pi restriction. In addition, we observed the increase of plasma 1,25
      dihydroxyvitamin D [1,25(OH)2D] levels by dietary Pi restriction, and the up
      regulation of ileal Fgf15 mRNA expression by 1,25(OH)2D3 and vitamin D receptor
      (VDR). Importantly, dietary Pi restriction-induced Fgf15 gene expression was
      prevented in VDR-knockout mice. Furthermore, diurnal variations of plasma
      triglyceride concentrations and hepatic mRNA expression of the bile acid
      synthesis enzyme Cyp7a1 as one of Fgf15 negative target genes was influenced by
      dietary Pi restriction. These results suggest that dietary Pi restriction up
      regulates ileal Fgf15 gene expression through 1,25(OH)2D3 and VDR, and may affect
      hepatic bile acid homeostasis. 

PMID- 24688220
TI  - Cooperative effects of soy isoflavones and carotenoids on osteoclast formation.
AB  - Osteoclasts play a major role in bone resorption. Several functional food
      components, such as soy isoflavones and carotenoids, are reported to inhibit
      osteoclast formation. However, the cooperative effect of functional foods or
      their constituents on bone metabolism has not been clarified. This study aimed to
      investigate the cooperative effect of soy isoflavones and carotenoids on
      osteoclast formation in vitro using cultures of RAW264 and bone marrow cells in
      the presence of receptor activator of nuclear factor kappa-B ligand. In RAW264
      cells, treatment with soy isoflavones (genistein or equol) or carotenoids (beta
      carotene) suppressed osteoclast formation. At 10 uM, genistein and equol
      inhibited RAW264 cell proliferation but did not affect cell viability. When 10 uM
      genistein or equol was combined with 0.1 uM beta-carotene, we observed an
      additive suppressive effect on osteoclast differentiation. Similar results were
      observed with bone marrow cell cultures. We found that 10 uM of zeaxanthin or
      lutein suppressed osteoclast formation singly, and further enhanced the
      suppressive effects of daidzein or genistein when administered in combination.
      These results suggest that the combination of soy isoflavones and carotenoids
      have an enhanced suppressive effect on osteoclast formation. This knowledge might
      be important in planning diet for bone health. 

PMID- 24688221
TI  - Supplementation of parenteral nutrition with fish oil attenuates acute lung
      injury in a rat model.
AB  - Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory
      properties and attenuates acute lung injury when administered in enternal
      nutrition. However, enteral nutrition is not always feasible. Therefore, we
      investigated the ability of parenteral nutrition supplemented with fish oil to
      ameliorate acute lung injury. Rats were infused with parenteral nutrition
      solutions (without lipids, with soybean oil, or with soybean oil and fish oil)
      for three days. Lipopolysaccharide (15 mg/kg) was then administered
      intratracheally to induce acute lung injury, characterized by impaired lung
      function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and
      upregulation of mRNAs for inflammatory mediators. Administration of parenteral
      nutrition supplemented with fish oil prior to lung insult improved gas exchange
      and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory
      mediators. Parenteral nutrition supplemented with fish oil also prolonged
      survival. To investigate the underlying mechanisms, leukotriene B4 and
      leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity.
      The neutrophils from rats treated with fish oil-rich parenteral nutrition
      released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than
      neutrophils isolated from rats given standard parenteral nutrition. Parenteral
      nutrition with fish oil significantly reduced lipopolysaccharide-induced lung
      injury in rats in part by promoting the synthesis of anti-inflammatory
      eicosanoids. 

PMID- 24688222
TI  - Relationship between blood levels of methyl donor and folate and mild cognitive
      impairment in Chinese patients with type 2 diabetes: a case-control study.
AB  - Type 2 diabetes is a risk factor for Alzheimer's disease and mild cognitive
      impairment. Folate insufficiency fosters a decline in the sole methyl donor, S
      adenosylmethionine, and decreases methylation potential, which is associated with
      Alzheimer's disease in non-diabetic patients. However, little is known in
      diabetic patients. We analyzed plasma levels of S-adenosylmethionine, S
      adenosylhomocysteine and serum level of folate in 100 elderly type 2 diabetic
      patients with and without mild cognitive impairment. S-adenosylmethionine/S
      adenosylhomocysteine ratio was used to reflect the methylation potential.
      Patients with mild cognitive impairment had significantly lower levels of S
      adenosylmethionine, folate and S-adenosylmethionine/S-adenosylhomocysteineratios.
      Furthermore, logistic regression analysis indicated the plasma S
      adenosylmethionine, S-adenosylmethionine/S-adenosylhomocysteine ratio and serum
      folate (OR, 0.96, 0.698, 0.72, respectively; p<0.05) were negatively associated
      with risk of mild cognitive impairment, even after adjusting for related
      covariates. In addition, folate level was positively correlated with S
      adenosylmethionine and the S-adenosylmethionine/S-adenosylhomocysteine ratio (r =
      0.38, 0.46, respectively; p<0.05) among patients within the middle tertile of
      folate levels (6.3-9.1 ug/L). These findings indicate mild cognitive impairment
      is associated with lower levels of S-adenosylmethionine, folate and weakened
      methylation potential; plasma S-adenosylmethionine and methylation potential may
      be predicted by serum folate within a suitable range of folate concentrations in
      diabetic patients. 

PMID- 24688223
TI  - The involvement of endoplasmic reticulum stress in bile acid-induced
      hepatocellular injury.
AB  - Secondary bile acids produced by enteric bacteria accumulate to high levels in
      the enterohepatic circulation and may contribute to the pathogenesis of
      hepatocellular injury. Relative hydrophobicity has been suggested to be an
      important determinant of the biological properties of these compounds, although
      the mechanism by which bile acids induce pathogenesis is not fully understood. On
      the other hand, endoplasmic reticulum stress has been shown to be involved in the
      induction and development of various pathogenic conditions. In this report, we
      demonstrated that the intensities of cytotoxicity and endoplasmic reticulum
      stress in HepG2 cells triggered by the bile acids tested were largely dependent
      on their hydrophobicity. The activation of caspase-3 and DNA fragmentation by
      treatment with chenodeoxycholic acid showed the contribution of apoptosis to
      cytotoxicity. Increases in intracellular calcium levels and the generation of
      reactive oxygen species stimulated by treatment with chenodeoxycholic acid
      contributed to endoplasmic reticulum stress. Bile acids also induced transforming
      growth factor-beta, a potent profibrogenic factor, which is known to induce
      hepatocyte apoptosis and ultimately liver fibrosis. In conclusion, our study
      demonstrated that bile acids induced endoplasmic reticulum stress, which in turn
      stimulated apoptosis in HepG2 cells, in a hydrophobicity-dependent manner. 

PMID- 24688224
TI  - Early activation of pulmonary TGF-beta1/Smad2 signaling in mice with acute
      pancreatitis-associated acute lung injury.
AB  - Acute lung injury is caused by many factors including acute pancreatitis. There
      is no specific therapy directed at underlying pathophysiological mechanisms for
      acute lung injury. Transforming growth factor-beta (TGF-beta) is involved in the
      resolution of lung injury in later phases of the disease. Some evidence exists
      demonstrating that TGF-beta not only is involved in the late stages, but also
      contributes to lung injury early on in the progress of the disease. Acute
      pancreatitis was induced using ductal ligation in mice. TGF-beta1, 2, and 3,
      TbetaRII, ALK-5, Smad2, 3, 4, and 7, and P-Smad2 expression in the lungs were
      analyzed at 9 and 24 h. We demonstrate that TGF- beta1 levels in the lungs of
      mice with acute pancreatitis increase as early as 9 h after induction. We
      observed an increased expression of ALK-5 in acute pancreatitis at both 9 and 24
      h. Inhibitory Smad7 expression was transiently increased at 9 h in acute
      pancreatitis, but reduced later at 24 h, with a concomitant increased nuclear
      translocation of phosphorylated Smad2. Our findings demonstrate activation of TGF
      beta signaling in the lungs as early as 24 h after acute pancreatitis, suggesting
      that TGF-beta may represent a potential therapeutic candidate in acute
      pancreatitis-induced acute lung injury.

PMID- 24688226
TI  - Of history, half-truths, and rheumatic fever.

PMID- 24688227
TI  - Elevated red cell distribution width is associated with delayed postoperative
      recovery after correction of Tetralogy of Fallot.
AB  - OBJECTIVE: To study the impact of red cell distribution width (RDW) on
      postoperative recovery after correction of Tetralogy of Fallot (TOF). BACKGROUND:
      Increased RDW indicates dysregulated erythropoiesis and predicts survival in
      critical illnesses that include idiopathic pulmonary artery hypertension and
      chronic heart failure. Myocardial injury and oxidative stress induced by
      cardiopulmonary bypass potentially contribute to prolonged recovery in post TOF
      repair patients. MATERIALS AND METHODS: Retrospective analysis of data on 94
      consecutive children with TOF undergoing corrective repair (January 2010-March
      2011) was done. RDW was higher for the study population when compared to
      acyanotic patients with ventricular septal defect (17.7 +/- 3.7 vs. 16.2 +/- 4.2;
      P < 0.001). The mean RDW obtained from 100 separate age-, sex-, and weight
      matched TOF patients (17.8) was chosen as a cut-off. Of 93 survivors (median age:
      12 (4-204) months, weight: 8.6 (3.2-70) kg), 29 patients with higher RDW (> 17.8)
      had a longer ICU stay (155.6 +/- 71.3 vs. 122.4 +/- 61.3 hours, P = 0.02),
      hospital stay (18.6 +/- 10.5 days vs. 13.4 +/- 6.5 days, P = 0.01), ventilation
      time (57.9 +/- 41.6 vs. 38.3 +/- 30.8 hours, P = 0.01), and more surgical site
      infection (24.1% vs. 6.2%, P = 0.01). On multivariate analysis only elevated RDW
      (other variables included age, weight, hemoglobin, hematocrit, and surgical
      support times) showed a significant association with hospital stay. CONCLUSIONS:
      Elevated RDW appears to be associated with prolonged recovery after TOF repair,
      the precise underlying mechanisms are worth investigating.

PMID- 24688225
TI  - Current trends in the monitoring and treatment of diabetic retinopathy in young
      adults.
AB  - The diagnosis and treatment of diabetic retinopathy (DR) in young adults have
      significantly improved in recent years. Research methods have widened
      significantly, for example, by introducing spectral optical tomography of the
      eye. Invasive diagnostics, for example, fluorescein angiography, are done less
      frequently. The early introduction of an insulin pump to improve the
      administration of insulin is likely to delay the development of diabetic
      retinopathy, which is particularly important for young patients with type 1
      diabetes mellitus (T1DM). The first years of diabetes occurring during childhood
      and youth are the most appropriate to introduce proper therapeutic intervention
      before any irreversible changes in the eyes appear. The treatment of DR includes
      increased metabolic control, laserotherapy, pharmacological treatment
      (antiangiogenic and anti-inflammatory treatment, enzymatic vitreolysis, and
      intravitreal injections), and surgery. This paper summarizes the up-to-date
      developments in the diagnostics and treatment of DR. In the literature search,
      authors used online databases, PubMed, and clinitrials.gov and browsed through
      individual ophthalmology journals, books, and leading pharmaceutical company
      websites. 

PMID- 24688228
TI  - Shape of the dilated aorta in children with bicuspid aortic valve.
AB  - BACKGROUND: The dilated aorta in adults with bicuspid aortic valve has been shown
      to have different shapes, but it is not known if this occurs in children. This
      observational study was performed to determine if there are different shapes of
      the dilated aorta in children with bicuspid aortic valve and their association
      with age, gender, hemodynamic alterations, and degree of aortic enlargement.
      METHODS: One hundred and eighty-seven echocardiograms done on pediatric patients
      (0 - 18 years) for bicuspid aortic valve, during 2008, were reviewed. Aortic
      valve morphology, shape/size of the aorta, and pertinent hemodynamic alterations
      were documented. Aortic dilation was felt to be present when at least one aortic
      segment had a z-score > 2.0; global aortic enlargement was determined by summing
      the aortic segment z-scores. The aortic shape was assessed by age, gender, valve
      morphology, and hemodynamic alterations. RESULTS: Aortic dilation was present in
      104/187 patients. The aorta had six different shapes designated from S1 through
      S6. There was no association between the aortic shape and gender, aortic valve
      morphology, or hemodynamic abnormalities. S3 was the most common after the age of
      six years and was associated with the most significant degree of global aortic
      enlargement. CONCLUSIONS: The shape of the dilated aorta in children with
      bicuspid aortic valve does not occur in a uniform manner and multiple shapes are
      seen. S2 and S3 are most commonly seen. As aortic dilation becomes more
      significant, a single shape (S3) becomes the dominant pattern.

PMID- 24688229
TI  - Amplatzer vascular plugs in congenital cardiovascular malformations.
AB  - BACKGROUND: Amplatzer vascular plugs (AVPs) are devices ideally suited to close
      medium-to-large vascular communications. There is limited published literature
      regarding the utility of AVPs in congenital cardiovascular malformations (CCVMs).
      AIMS: To describe the use of AVPs in different CCVMs and to evaluate their safety
      and efficacy. MATERIALS AND METHODS: All patients who required an AVP for the
      closure of CCVM were included in this retrospective review of our catheterization
      laboratory data. The efficacy and safety of AVPs are reported. RESULTS: A total
      of 39 AVPs were implanted in 31 patients. Thirteen (33%) were AVP type I and 23
      (59%) were AVP type II. AVP type III were implanted in two patients and type IV
      in one patient. The major indications for their use included closure of pulmonary
      arteriovenous malformation (AVM) (n = 7), aortopulmonary collaterals (n = 7),
      closure of a patent Blalock-Taussig shunt (n = 5), systemic AVM (n = 5), coronary
      AVM (n = 4), patent ductus arteriosus (PDA) (n = 3), pulmonary artery aneurysms
      (n = 3), and venovenous collaterals (n = 2). Deployment of the AVP was done
      predominantly via the 5 - 7F Judkin's right coronary guide catheter. Overall 92%
      of the AVPs could be successfully deployed and resulted in occlusion of the
      target vessel in all cases, within 10 minutes. No procedure-related or access
      site complication occurred. CONCLUSIONS: AVPs are versatile, easy to use, and
      effective devices to occlude the vascular communications in a variety of
      settings. AVP II is especially useful in the closure of tubular structures with a
      high flow.

PMID- 24688230
TI  - Pulmonary valve regurgitation following balloon valvuloplasty for pulmonary valve
      stenosis: Single center experience.
AB  - BACKGROUND: Pulmonary valve regurgitation following balloon valvuloplasty for
      moderate to severe pulmonary valve stenosis is a known late outcome of this
      procedure. OBJECTIVE: The aim of the study was to characterise the status of
      pulmonary regurgitation on follow up after pulmonary valve balloon dilatation
      (PVBD), and to study the determinant of the severity of PR. MATERIALS AND
      METHODS: We retrospectively reviewed 50 consecutive patients, aged 2 days to 18
      years, with isolated pulmonary valve stenosis, who had undergone PVBD in 2004
      2009 and were assessed with follow-up Doppler echocardiography. The impact of
      balloon to annulus ratio, age, and valve anatomy on the late development of
      moderate and severe pulmonary valve regurgitation following balloon valvuloplasty
      was analysed. RESULTS: Six patients (12%) had no pulmonary valve regurgitation;
      32 (64%) had mild, 9 (18%) had moderate, and 3 (6%) had severe pulmonary valve
      regurgitation at a mean follow-up of 4 years. Balloon to annulus ratio, age, and
      valve anatomy were not statistically significant predictors for moderate and
      severe pulmonary valve regurgitation. CONCLUSIONS: The majority of patients in
      our population had mild pulmonary valve regurgitation. Moderate to severe
      pulmonary valve regurgitation was well tolerated at midterm follow-up. Age,
      balloon to annulus ratio, and valve anatomy were not statistically significant
      predictors for the late development of moderate and severe valve regurgitation.
      Large and longer follow-up studies are needed to address this question.

PMID- 24688231
TI  - Estimating intracardiac and extracardiac shunting in the setting of complex
      congenital heart disease.
AB  - Complex congenital heart disease (CHD) is associated with significant morbidity
      worldwide. Managing hypoxemia in these populations can be difficult, particularly
      in the setting of cyanotic CHD. However, the presence of additional extracardiac
      shunts secondary to acute respiratory disease can be very challenging to manage.
      Before understanding how to deal with hypoxemia in patients with dual shunts, one
      needs to understand the physiology and diagnosis related to the individual shunts
      and apply this knowledge to the patient as a whole. 

PMID- 24688232
TI  - How best to explain unexpected arrangements of the atrioventricular valves?

PMID- 24688233
TI  - What are double-outlet left atrium and double-outlet right atrium?

PMID- 24688234
TI  - Double-outlet left atrium: Ventriculo-atrial malalignment defect.
AB  - A four-month-old female infant presented with heart failure and cyanosis. On
      echocardiography, there was no outlet to the right atrium except an atrial septal
      defect and the left atrium drained into the respective ventricles by two
      atrioventricular valves. The case is reported for its rarity, with a brief
      literature review. 

PMID- 24688235
TI  - An unusual example of isolated double-orifice tricuspid valve.
AB  - Double-orifice tricuspid valve (DOTV) is a very rare congenital cardiac anomaly.
      We report an unusual example of DOTV where one orifice was committed to the left
      ventricle. This was identified preoperatively and managed surgically. 

PMID- 24688236
TI  - Submitral aneurysm: An antenatal diagnosis.
AB  - We describe the echocardiographic features of submitral aneurysm in a 26 week old
      fetus. The diagnosis was confirmed on neonatal echocardiography. 

PMID- 24688237
TI  - Unusual right ventricle aneurysm and dysplastic pulmonary valve with mitral valve
      hypoplasia.
AB  - We report a newborn with an unusual combination of aneurysmally dilated thin
      walled right ventricle with hypertrophy of the apical muscles of the right
      ventricle. There was narrow pulmonary annulus, pulmonary regurgitation, and
      hypoplasia of the mitral valve and left ventricle. We propose that this heart
      represents a partial form of Uhl's anomaly. 

PMID- 24688238
TI  - Off-pump atrial septostomy with thoracoscopic scissors under transesophageal
      echocardiography guidance.
AB  - Selected children with congenital heart defects undergoing palliative closed
      heart procedures require a cardiopulmonary bypass (CPB) run only for the purpose
      of creating an inter-atrial communication. We report a simple technique of atrial
      septostomy using thoracoscopy scissors under transesophageal echocardiography
      guidance without the need for CPB. 

PMID- 24688239
TI  - Percutaneous device closure of persistent ductus venosus presenting with
      hemoptysis.
AB  - An eight-year-old boy was evaluated for unexplained hemoptysis and cyanosis. A
      contrast echocardiogram was suggestive of pulmonary arteriovenous fistula.
      Further evaluation revealed persistent ductus venosus (PDV) and aortopulmonary
      collaterals. Both the PDV and aortopulmonary collaterals were closed
      percutaneously. PDV is amenable for device closure after detailed anatomical
      evaluation. Prior to closure, it is important to ensure adequate portal vein
      arborization into the liver and normal portal pressure after test balloon
      occlusion. 

PMID- 24688240
TI  - Epicardial deployment of right ventricular disk during perventricular device
      closure in a child with apical muscular ventricular septal defect.
AB  - We report a successful perventricular closure of an apical muscular ventricular
      septal defect (mVSD) by a modified technique. An eight-month-old infant, weighing
      6.5 kilograms, presented with refractory heart failure. The transthoracic
      echocardiogram showed multiple apical mVSDs with the largest one measuring 10 mm.
      perventricular device closure using a 12 mm Amplatzer mVSD occluder was planned.
      The left ventricular disk was positioned approximating the interventricular
      septum; however, the right ventricular (RV) disk was deployed on the free wall of
      the RV due to an absent apical muscular septum and a small cavity at the apex.
      The RV disk of the device was covered using an autologous pericardium. His heart
      failure improved during follow-up. 

PMID- 24688241
TI  - Surgical removal of a left ventricular myxoma in an infant.
AB  - Left ventricular (LV) myxoma is particularly rare in children and has not been
      reported in infants. A five-month-old baby presented with a myxoma arising from
      the anterior, lateral, and superior aspect of the LV, causing severe left
      ventricular outflow tract obstruction. The LV was accessed through the conal
      septum after opening the right ventricular outflow. The child had transient
      complete heart block in the postoperative period. There was no recurrence of
      tumor at the nine-month follow-up. 

PMID- 24688242
TI  - Remission of congenital complete heart block without anti-Ro/La antibodies: A
      case report.
AB  - Anti-Ro/La negative congenital heart block (CHB) is uncommon. We report one such
      case of CHB, with no associated structural heart disease or maternal
      autoantibodies. The heart block reverted to sinus rhythm spontaneously at two
      weeks of age, and the patient remains in sinus rhythm at a one year followup.
      Whether patients with antibody negative complete heart block have a different
      clinical course is conjectural. 

PMID- 24688243
TI  - Transjugular closure of a two-hole atrial septal defect in a child with iliac
      vein thrombosis.
AB  - The internal jugular vein is not a typical vascular access line during the
      percutaneous closure of an atrial septal defect. We report the closure of a
      double atrial septal defect with a single device, using a transjugular venous
      approach, in a child with an inferior vena cava obstructed by a thrombosis due to
      previous cardiac catheterization. That the transjugular venous approach can be
      used as a possible alternative during the transcatheter closure of an atrial
      septal defect in children, when the inferior vena cava access is not possible. 

PMID- 24688244
TI  - Transcatheter closure of large right pulmonary artery-to-left atrial fistula.
AB  - We report the successful transcatheter closure of right pulmonary artery fistula
      to left atrium in a six-year-old boy, who had presented with cyanosis and
      shortness of breath. The two-dimensional echocardiogram with bubble contrast
      study demonstrated the communication between right pulmonary artery and left
      atrium. Computerized tomography confirmed the diagnosis and delineated the
      anatomy. The fistula was closed successfully by a transcatheter trans-septal
      approach using an 18/20 duct occluder. 

PMID- 24688245
TI  - Unusual systemic venous Collateral channels to left atrium causing desaturation
      after Fontan operation closed percutaneously.
AB  - We present an unusual cause of progressive cyanosis in a child appearing 2 years
      after successful Fontan surgery for tetralogy of Fallot with hypoplastic right
      ventricle. The cause of cyanosis was identified as one large venous channel
      draining into the left atrium. The channel was closed by Amplatzer vascular plug
      resulting in improvement of oxygen saturation. 

PMID- 24688246
TI  - Hemitruncus with ventricular septal defect in a 6-year-old child.
AB  - We report a 6-year-old girl with anomalous origin of the right pulmonary artery
      from the aorta associated with a large ventricular septal defect. The challenges
      in the assessment of operability and issues in the surgical management are
      discussed. 

PMID- 24688247
TI  - Coronary artery thrombus resulting in sudden cardiac death in an infant with
      Kawasaki disease and giant coronary artery aneurysms.
AB  - We report a case of a six-month-old Hispanic male infant who had Kawasaki disease
      and coronary artery aneurysms on echocardiography. He died suddenly five months
      later in spite of aggressive medical therapy. Autopsy showed extensive coronary
      artery thrombosis. Giant coronary artery aneurysms need diligent follow up as
      they pose significant risks including risk of thrombus, myocardial infarction and
      sudden death. 

PMID- 24688248
TI  - VACTERL association with double-chambered left ventricle: A rare occurrence.
AB  - VACTERL association is a non-random association of birth defects of unknown
      etiology derived from structures of embryonic mesoderm. The common cardiac
      defects seen with VACTERL association are ventricular septal defects, atrial
      septal defects, and tetralogy of Fallot. We present a 2-year-old child with
      VACTERL association in whom we detected double-chambered left ventricle on
      transthoracic echocardiography. 

PMID- 24688249
TI  - A rare pediatric cardiac anomaly: Quadricuspid aortic valve with aortic
      regurgitation.
AB  - A quadricuspid aortic valve is rarely diagnosed in children, but it can be
      associated with significant aortic regurgitation. It is important for pediatric
      cardiologists to be aware of this pathologic entity. We present a nine-year-old
      male, diagnosed with a quadricuspid aortic valve and mild aortic regurgitation. 

PMID- 24688250
TI  - Supratricuspid obstructive membrane in congenitally corrected transposition of
      the great arteries.
AB  - Obstructive lesions in the inflow of the systemic ventricle in congenitally
      corrected transposition of the great arteries are rare. It is important to
      identify such lesion which could alter the surgical outcome if not recognized. We
      report the echocardiographic findings in a patient with supratricuspid
      obstructive membrane with corrected transposition of the great arteries. 

PMID- 24688251
TI  - Re. Treating hypoplastic left heart syndrome in emerging economies: Heading the
      wrong way?

PMID- 24688252
TI  - Selected summaries.

PMID- 24688254
TI  - The correlation of routine tear function tests and conjunctival impression
      cytology in dry eye syndrome.
AB  - PURPOSE: To establish the strength of the association between routine tear
      function tests and conjunctival impression cytology (CIC) and to determine
      whether they simulate the morphological and cytological changes that occur on the
      ocular surface in dry eye. What are the sensitivity, specificity and positive
      predictive values of these tests when CIC is considered the gold standard?
      METHODS: The tear film profile included tear film break up time (TBUT),
      Schirmer's-1, Rose Bengal scores (RBS), and impression cytology. CIC samples were
      obtained from the inferior bulbar conjunctiva and stained with periodic acid
      Schiff and counter stained with hematoxylin and eosin. RESULTS: The mean
      Schirmer's value was 11.66 +/- 5.90 in patients and 17.17 +/- 2.97 in controls (p
      < 0.001). The mean TBUT in participants was 8.88 +/- 3.54 and 13.53 +/- 2.12 in
      controls (p < 0.001). Patients had a mean goblet cell density (GCD) of 490 +/-
      213, while the value for controls was 1,462 +/- 661 (p < 0.001). Abnormal CIC was
      observed in 46.7% cases of dry eye and in 32.8% of controls. The correlation
      coefficient (L) for Schirmer's was 0.2 and 0.24 for participants and controls,
      respectively, while TBUT values were 0.26 and 0.38, RBS were 0.5 and 0.5, and GCD
      was 0.8 and 0.6 in cases and controls, respectively. CONCLUSIONS: GCD, RBS, and
      TBUT were better predictors of morphological and cytological changes in the
      conjunctiva than Schirmer's in dry eye syndrome. The sensitivity of tear function
      tests in diagnosing dry eye was TBUT > Schirmer's > RBS, and the specificity was
      Schirmer's > TBUT > RBS in decreasing order when CIC was considered the gold
      standard.

PMID- 24688253
TI  - Current practice pattern for dry eye patients in South Korea: a multicenter
      study.
AB  - PURPOSE: To assess current practice patterns for dry eye patients in South Korea
      and to evaluate the preference according to the ages and clinic types of
      physicians. METHODS: Dry eye patients (n = 1,612) were enrolled in this
      multicenter cross-sectional, observational study. The severity level of dry eye
      patients was classified based on the Korean guidelines for dry eye treatment. The
      medical records of the enrolled dry eye patients were evaluated, and the practice
      styles and the preferences were analyzed according to the ages and clinic types
      of physicians. RESULTS: Of all patients, dry eye level 1 was most common (47.5%),
      followed by level 2 (33.5%), level 3 (9.1%), and level 4 (1.1%). Topical anti
      inflammatory agents were used in 70.7% of patients with dry eye level 2 and in
      80.6% of patients at levels 3 and 4. Topical anti-inflammatory agents were also
      used in 48.7% of patients with dry eye level 1. Preservative-free artificial
      tears were preferred at all dry eye levels. The use of topical anti-inflammatory
      agents did not differ with investigator ages, but older physicians preferred
      preserved artificial tears more than younger ones. Physicians at referral
      hospitals also tended to use topical anti-inflammatory agents and preservative
      free artificial tears earlier, beginning at dry eye level 1, than those who
      worked at private eye clinics. CONCLUSIONS: Topical anti-inflammatory agents were
      commonly prescribed for the treatment of dry eye patients in South Korea, even
      from dry eye level 1. Preservative-free artificial tears were preferred at all
      dry eye levels. Practice styles differed somewhat depending on the ages and
      clinic types of physicians.

PMID- 24688255
TI  - Comparison of surgically-induced astigmatism after combined phacoemulsification
      and 23-gauge vitrectomy: 2.2-mm vs. 2.75-mm cataract surgery.
AB  - PURPOSE: The 2.2-mm microincision cataract surgery and small-gauge vitrectomy
      system is known to result in less surgically-induced astigmatism (SIA) in
      comparison to conventional surgical methods. We compared the amounts of SIA after
      combined phacoemulsification and 23-gauge transconjunctival sutureless vitrectomy
      (23G-TSV) using the 2.2-mm microincision and 2.75-mm standard incision methods.
      METHODS: We studied 59 patients (61 eyes) who underwent combined
      phacoemulsification and 23G-TSV from November 2008 to September 2012. Twenty
      eight patients (28 eyes) underwent 2.2-mm microincision coaxial
      phacoemulsification, and 31 patients (33 eyes) underwent 2.75-mm standard
      incision phacoemulsification. SIA was evaluated using Naeser's polar method with
      the simulated keratometric values obtained from corneal topography. Preoperative
      and 1-week and 1-month postoperative KP (Naeser's polar value along the specific
      axis) and DeltaKP values were compared between the 2.2-mm microincision and 2.75
      mm standard incision groups. RESULTS: One week after surgery, both groups
      exhibited similar amounts of SIA (-DeltaKP[120], 0.40 +/- 0.41 vs. 0.51 +/- 0.56
      diopters [D]; p = 0.390). One month after surgery, however, the amount of SIA was
      significantly smaller in the 2.2-mm microincision group as compared to the 2.75
      mm standard incision group (-DeltaKP[120], 0.31 +/- 0.54 vs. 0.56 +/- 0.42 D; p =
      0.045). CONCLUSIONS: In combined phacoemulsification with 23G-TSV, 2.2-mm
      microincision coaxial phacoemulsification induces less SIA than does 2.75-mm
      standard coaxial phacoemulsification.

PMID- 24688256
TI  - Reproducibility of peripapillary retinal nerve fiber layer thickness measured by
      spectral domain optical coherence tomography in pseudophakic eyes.
AB  - PURPOSE: To assess the reproducibility of circumpapillary retinal nerve fiber
      layer (cpRNFL) thickness measurement (measurement agreement) and its color-coded
      classification (classification agreement) by Cirrus spectral domain optical
      coherence tomography (OCT) in pseudophakic eyes. METHODS: Two-hundred five
      participants having glaucoma or glaucoma suspected eyes underwent two repeated
      Cirrus OCT scans to measure cpRNFL thickness (optic disc cube 200 * 200). After
      classifying participants into three different groups according to their lens
      status (clear media, cataract, and pseudophakic), values of intra-class
      coefficient (ICC), coefficient of variance, and test-retest variability were
      compared between groups for average retinal nerve fiber layer (RNFL) thicknesses
      and that corresponding to four quadrant maps. Linear weighted kappa coefficients
      were calculated as indicators of agreement of color code classification in each
      group. RESULTS: ICC values were all excellent (generally defined as 0.75 to 1.00)
      for the average and quadrant RNFL thicknesses in all three groups. ICC values of
      the clear media group tended to be higher than those in the cataract and
      pseudophakic groups for all quadrants and average thickness. Especially in the
      superior and nasal quadrants, the ICC value of the cataract group was
      significantly lower than that of the clear media and pseudophakic groups. For
      average RNFL thickness, classification agreement (kappa) in three groups did not
      show a statistically significant difference. For quadrant maps, classification
      agreement (kappa) in the clear media group was higher than those in the other two
      groups. CONCLUSIONS: Agreement of cpRNFL measurement and its color code
      classification between two repeated Cirrus OCT scans in pseudophakic eyes was as
      good as that in eyes with clear crystalline lens. More studies are required to
      ascertain the effect of lens status on the reproducibility of Cirrus OCT
      according to different stages of glaucoma patients.

PMID- 24688257
TI  - Changes in the accommodation-convergence relationship after the Artisan phakic
      intraocular lens implantation for myopic patients.
AB  - PURPOSE: To evaluate the change of accommodation-convergence parameters after
      implantation of Artisan phakic intraocular lens (PIOL). METHODS: Prospective
      study for the patients with the Artisan PIOL implantation was performed. A total
      of 37 patients (3 males and 34 females) enrolled the study. Preoperatively,
      convergence amplitude, the stimulus accommodative convergence per unit of
      accommodation (AC/A) ratio and the near point of convergence (NPC) were
      evaluated. After the Artisan PIOL implantation, the identical evaluations were
      repeated at 1 week, 1, 3, and 6 months after the surgery. RESULTS: Mean age was
      24.3 +/- 4.8 years old, and preoperative refractive error was -8.92 +/- 4.13
      diopters (D). After the implantation, mean refractive errors significantly
      decreased to within +/-1.00 D, and noticeable complications were not found. The
      convergence amplitude and the stimulus AC/A ratio increased 1 month after the
      surgery, but progressively stabilized afterward to near preoperative values. NPC
      didn't show any significant change over follow-up period up to 6 months.
      CONCLUSIONS: These results regarding implantation of the Artisan PIOL revealed
      the increase of accommodation-convergence relationship within first 1 month after
      the surgery, but progressive stabilization was noted during follow-up periods.

PMID- 24688258
TI  - Ocular findings in children with single umbilical artery: a case series of 14
      children.
AB  - PURPOSE: Single umbilical artery (SUA) is the most common malformation of the
      umbilical cord. However, there have been no studies on the ocular findings in
      SUA, except for one case report. This study aimed to investigate the ocular
      findings in children with SUA. METHODS: Fourteen children (eight boys and six
      girls) with SUA were evaluated retrospectively. All children underwent a complete
      ophthalmologic examination. RESULTS: The prevalence of abnormal ocular findings
      in children was up to 42.9%. Refractive errors are detected in four eyes (14.3%):
      myopia >=-1.50 diopters (D) in one eye (3.6%) and hyperopia >=+2.00 D in three
      eyes (10.7%). Epiblepharon was found in three children (21.4%), and strabismus
      was detected in one child (7.1%). CONCLUSIONS: Approximately half of the children
      with SUA showed abnormal ocular findings, therefore, our case series highlight
      the need for a comprehensive ocular examination and larger prospective research
      studies in young patients with SUA.

PMID- 24688259
TI  - Specific visual symptoms and signs of Meares-Irlen syndrome in Korean.
AB  - PURPOSE: To discriminate the visual symptoms and signs of Meares-Irlen syndrome
      (MIS) and nonspecific dyslexia from other ophthalmologic diseases (NODs).
      METHODS: Forty-five patients were enrolled. Thirty four of the patients with MIS
      whose symptoms improved with tinted lenses comprised MIS group. The other 11
      patients whose reading difficulty improved with other ocular therapy and did not
      require tinted lenses comprised NODs group. The main symptoms causing dyslexia
      and associated ocular diseases were evaluated. RESULTS: The mean age was 17.9 +/-
      9.5 years in MIS group, and 19.3 +/- 11.0 years in NODs group. In MIS group, the
      most common symptoms while reading were difficulty to move lines (85%), doubling
      (53%), and difficulty in bright condition (27%). On the other hand, blurring was
      the most common symptom in NODs group (45%). The associated ocular diseases in
      the two groups were refractive error (79% and 73%), dry eye (29% and 18%), and
      exophoria (6% and 27%), respectively. CONCLUSIONS: Doubling, difficulty to move
      lines, and difficulty in bright condition while reading are main specific
      symptoms in MIS compared to nonspecific dyslexia from other ophthalmologic
      disorders.

PMID- 24688260
TI  - Using ImageJ to evaluate optic disc pallor in traumatic optic neuropathy.
AB  - PURPOSE: To evaluate optic disc pallor using ImageJ in traumatic optic neuropathy
      (TON). METHODS: This study examined unilateral TON patients. The optic disc was
      divided into 4 quadrants (temporal, superior, nasal, and inferior), consistent
      with the quadrants on optical coherence tomography (OCT) retinal nerve fiber
      layer (RNFL) thickness maps. Optic disc photography was performed and disc pallor
      was quantified using gray scale photographic images imported into ImageJ
      software. The correlation between optic disc pallor and RNFL thickness was
      examined in each quadrant. RESULTS: A total of 35 patients (31 male, 4 female)
      were enrolled in the study. The mean participant age was 34.8 +/- 15.0 years
      (range, 5 to 63 years). Overall RNFL thickness decreased in 6 patients, with
      thinning most often occurring in the inferior quadrant (28 of 35 eyes). There was
      a significant correlation between optic disc pallor and RNFL thickness (superior,
      rho = -0.358, p = 0.04; inferior, rho = -0.345, p = 0.04; nasal, rho = -0.417, p
      = 0.01; temporal, rho = -0.390, p = 0.02). The highest level of correspondence
      between disc pallor and RNFL thickness values outside of the normative 95th
      percentiles was 39.3% and occurred in the inferior quadrant. CONCLUSIONS: Optic
      disc pallor in TON was quantified with ImageJ and was significantly correlated
      with RNFL thickness abnormalities. Thus, ImageJ evaluations of disc pallor may be
      useful for evaluating RNFL thinning, as verified by OCT RNFL analyses.

PMID- 24688261
TI  - Effect of macrophage migration inhibitory factor on corneal sensitivity after
      laser in situ keratomileusis in rabbit.
AB  - PURPOSE: To investigate the effect of macrophage migration inhibitory factor
      (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery.
      METHODS: New Zealand white rabbits were used in this study. A hinged corneal flap
      (160-um thick) was created with a microkeratome, and -3.0 diopter excimer laser
      ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells
      and surrounding inflammatory cells were analyzed using reverse transcription
      polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the
      rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF
      (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL),
      neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia
      inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative
      and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed
      using the Cochet-Bonnet esthesiometer. RESULTS: Expression of MIF mRNA was 2.5
      fold upregulated in the corneal epithelium and 1.5-fold upregulated in the
      surrounding inflammatory cells as compared with the control eyes. Preoperative
      baseline corneal sensitivity was 40.56 +/- 2.36 mm. At two weeks after LASIK,
      corneal sensitivity was 9.17 +/- 5.57 mm in the BSS treated group, 21.92 +/- 2.44
      mm in the MIF treated group, and 22.42 +/- 1.59 mm in the neuronal growth factors
      treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p <
      0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK,
      corneal sensitivity was 15.00 +/- 9.65, 35.00 +/- 5.48, and 29.58 +/- 4.31 mm
      respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p =
      0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone
      could achieve as much of an effect on recovery of corneal sensation as treatment
      with combination of NGF, NT-3, IL-6, and LIF. CONCLUSIONS: Topically administered
      MIF plays a significant role in the early recovery of corneal sensitivity after
      LASIK in the experimental animal model.

PMID- 24688262
TI  - Ranibizumab injection for corneal neovascularization refractory to bevacizumab
      treatment.
AB  - Vascular endothelial growth factor inhibitor is an emerging therapeutic modality
      for various ocular diseases with neovascularization (NV). However, for corneal
      NV, controversy remains regarding whether bevacizumab or ranibizumab is superior.
      A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory
      corneal NV despite two previous subconjunctival and intrastromal bevacizumab
      injections, received two subconjunctival and intrastromal ranibizumab injections.
      Six months postoperatively, there was significant regression of the neovascular
      area and vessel caliber. Here, the authors report a case of improvement in
      corneal NV with subconjunctival and intrastromal ranibizumab injections, which
      was previously refractory to bevacizumab injection. The findings may suggest a
      new prospect in treating corneal NV. 

PMID- 24688263
TI  - Sutureless intrascleral pocket technique of transscleral fixation of intraocular
      lens in previous vitrectomized eyes.
AB  - In this case series, we assessed a new technique, the intrascleral pocket
      procedure of transscleral fixation (TF) of the intraocular lens (IOL) in post
      vitrectomized eyes. We performed the transscleral fixation of IOL in four aphakic
      patients who underwent pars plana vitrectomy. Two points 180 degrees  apart were
      marked at the limbus. A 2-mm-sized intrascleral pocket was created by lamellar
      dissection using a crescent blade without conjunctival dissection. A 2.8-mm clear
      corneal incision (CCI) was made using a keratome. Prolene sutures were
      exteriorized through the CCI pocket and a three-piece foldable acrylic IOL was
      injected via CCI and the ends of the haptics were exteriorized through the CCI.
      The prolene sutures for each haptic in the intrascleral pocket bed were then tied
      and knots were buried under scleral flaps. No patient had complaints such as
      conjunctival irritation, and visual acuity was almost identical to preoperative
      best-corrected visual acuity at day 1 postoperatively. IOLs were well placed
      without tilting or subluxation. They had no wound dehiscence or endophthalmitis
      postoperatively. The intrascleral pocket procedure of TF without the need for
      conjunctival dissection is a successful method for sulcus fixation in post
      vitrectomized eyes predisposed to developing glaucoma.

PMID- 24688264
TI  - Bilateral acute anterior uveitis and optic disc edema following a snake bite.
AB  - The authors wish to report a case of bilateral acute anterior uveitis and optic
      disc edema following a hemotoxic snake bite, in order to highlight the
      concomitant occurrence of these conditions and the potential adverse effects of
      anti-snake venom (ASV). A 35-year-old male was bitten by a viper at seventeen
      thirty hours, and was started on ASV. Two days following treatment he experienced
      sudden onset redness and painful diminution of vision in both eyes (OU). On
      examination, the patient's visual acuity (VA) in OU was 20/200. Examination
      revealed fresh keratic precipitates, cells, and flare in the anterior chamber
      (AC), posterior synechiae, sluggish and ill-sustained pupillary reaction, and
      hyperemic, edematous disc with blurred margins in OU. He was started on topical
      steroids, cycloplegics and intravenous methylprednisolone. Following treatment,
      the patient showed improvement and was continued on topical medications and oral
      prednisolone tapered over 3 weeks, after which VA OU improved, the AC showed no
      cells and flare and disc edema resolved. Uveitis and optic disc edema in snake
      bite can either be due to the direct toxic effects of the venom or the effect of
      ASV. Steroids have a beneficial role in the management of these symptoms.

PMID- 24688265
TI  - Acetazolamide for cystoid macular oedema in Bietti crystalline retinal dystrophy.
AB  - Bietti crystalline retinal dystrophy is a rare, inherited disorder whose hallmark
      is the presence of retinal crystal deposits associated with later chorioretinal
      degeneration. This condition may rarely be complicated by the development of
      cystoid macular oedema leading to rapid visual decline. Currently, treatment
      options for this complication of Bietti dystrophy are limited and the visual
      prognosis is poor. Here, we present a case of cystoid macular oedema associated
      with Bietti dystrophy that was successfully diagnosed using multimodal imaging
      techniques including optical coherence tomography and fluorescein angiography.
      These modalities confirmed the diagnosis of macular oedema and excluded other
      possible causes of oedema such as choroidal neovascularisation. In this patient,
      cystoid macular oedema was resolved with oral acetazolamide therapy, a treatment
      that has not been previously reported in this context. Acetazolamide treatment
      resulted in oedema resolution and improvement in visual function, and can be
      considered a therapeutic option for other patients with Bietti dystrophy who
      develop cystoid macular oedema. 

PMID- 24688266
TI  - Reversal of early central retinal vein occlusion by alleviating optic nerve edema
      with an intravitreal dexamethasone implant.
AB  - This case describes the reversal of early central retinal vein occlusion (CRVO)
      with disc swelling after intravitreal dexamethasone implant (Ozurdex) injection.
      A 44-year-old female presented with sudden-onset intermittent blurred vision in
      her left eye. Fundus examination revealed multiple retinal hemorrhages without
      macular edema (ME). Two weeks later, an increased number of retinal hemorrhages
      with severe disc swelling were noted with still no sign of ME. An intravitreal
      dexamethasone implant was injected. Five days later, there were improvements in
      disc swelling and retinal hemorrhage. One month later, her subjective visual
      symptoms were completely improved, and fundus examination revealed marked
      improvement along with almost complete resolution of disc swelling. Intravitreal
      dexamethasone implant injection may potentially change the natural course of CRVO
      progression and its various subsequent complications.

PMID- 24688267
TI  - A case of ocular myasthenia gravis presenting as double depressor palsy.
AB  - A 65-year-old man who had been experiencing diplopia in front and down gaze for
      15 days visited our hospital. Hypertropia was noted in the patient's left eye,
      and limitation of depression was found in the adduction, primary gaze, and
      abduction. Brain magnetic resonance imaging showed no remarkable findings. Two
      weeks after the first visit, the patient complained of ptosis in the left eye. An
      ice test was performed and the ptosis was resolved after the test. Then, anti
      acetylcholine receptor binding antibody levels were checked and found to be
      slightly elevated. We prescribed methylprednisolone per os 24 mg for 2 weeks, and
      his symptoms improved after the 2-week treatment. Five weeks after his first
      visit, the patient showed an ortho result in the alternate prism cover test and
      normal ocular movements. This may be the first case in which ocular myasthenia
      gravis presented as double depressor palsy, and in such cases, the possibility of
      ocular myasthenia gravis should be considered to rule out double depressor palsy.

PMID- 24688268
TI  - Biochemical and immunological markers of over-training.
AB  - Athletes fail to perform to the best of their ability if they become infected,
      stale, sore or malnourished. Excessive training with insufficient recovery can
      lead to a debilitating syndrome in which performance and well being can be
      affected for months. Eliminating or minimizing these problems by providing advice
      and guidelines on training loads, recovery times, nutrition or pharmacological
      intervention and regular monitoring of athletes using an appropriate battery of
      markers can help prevent the development of an overtraining syndrome in athletes.
      The potential usefulness of objective physiological, biochemical and
      immunological markers of overtraining has received much attention in recent
      years. Practical markers would be ones that could be measured routinely in the
      laboratory and offered to athletes as part of their sports science and medical
      support. The identification of common factors among overtrained athletes in
      comparison with well-trained athletes not suffering from underperformance could
      permit appropriate intervention to prevent athletes from progressing to a more
      serious stage of the overtraining syndrome. To date, no single reliable objective
      marker of impending overtraining has been identified. Some lines of research do,
      however, show promise and are based on findings that overtrained athletes appear
      to exhibit an altered hormonal response to stress. For example, in response to a
      standardized bout (or repeated bouts) of high intensity exercise, overtrained
      athletes show a lower heart rate, blood lactate and plasma cortisol response.
      Several immune measures that can be obtained from a resting blood sample (e.g.
      the expression of specific cell surface proteins such as CD45RO+ on T
      lymphocytes) also seem to offer some hope of identifying impending overtraining.
      If an athlete is suspected of suffering from overtraining syndrome, other
      measures will also required, if only to exclude other possible causes of
      underperformance including post-viral fatigue, glandular fever, clinical
      depression, poor diet, anaemia, asthma, allergies, thyroid disorders, myocarditis
      and other medical problems interfering with recovery. 

PMID- 24688269
TI  - Complex training: a brief review.
AB  - The effectiveness of plyometric training is well supported by research. Complex
      training has gained popularity as a training strategy combining weight training
      and plyometric training. Anecdotal reports recommend training in this fashion in
      order to improve muscular power and athletic performance. Recently, several
      studies have examined complex training. Despite the fact that questions remain
      about the potential effectiveness and implementation of this type of training,
      results of recent studies are useful in guiding practitioners in the development
      and implementation of complex training programs. In some cases, research suggests
      that complex training has an acute ergogenic effect on upper body power and the
      results of acute and chronic complex training include improved jumping
      performance. Improved performance may require three to four minutes rest between
      the weight training and plyometrics sets and the use of heavy weight training
      loads. 

PMID- 24688271
TI  - Changes in body fat content of top-level soccer players.

PMID- 24688270
TI  - Effects of a carbohydrate-electrolyte drink on specific soccer tests and
      performance.
AB  - The aim of this study was to examine the effects of a carbohydrate-electrolyte
      drink on specific soccer tests and performance. Twenty-two professional male
      soccer players volunteered to participate in the study. The players were
      allocated to two assigned trials ingesting carbohydrate-electrolyte drink (7%
      carbohydrates, sodium 24 mmol.l-1, chloride 12 mmol.l-1, potassium 3 mmol.l-1) or
      placebo during a 90 min on-field soccer match. The trials were matched for
      subjects' age, weight, height and maximal oxygen uptake. Immediately after the
      match, players completed four soccer-specific skill tests. Blood glucose
      concentration [mean (SD)] was higher at the end of the match-play in the
      carbohydrate-electrolyte trial than in the placebo trial (4.4 (0.3) vs. 4.0 (0.3)
      mmol.l-1, P < 0.05). Subjects in the carbohydrate-electrolyte trial finished the
      specific dribble test faster in comparison with subjects in the placebo trial
      (12.9 (0.4) vs. 13.6 (0.5) s, P < 0.05). Ratings of the precision test were
      higher in the carbohydrate-electrolyte trial as compared to the placebo trial
      (17.2 (4.8) vs. 15.1 (5.2), P < 0.05) but there were no differences in
      coordination test and power test results between trials. The main finding of the
      present study indicates that supplementation with carbohydrate-electrolyte
      solution improved soccer-specific skill performance and recovery after an on
      field soccer match compared with ingestion of placebo. This suggests that soccer
      players should consume carbohydrate-electrolyte fluid throughout a game to help
      prevent deterioration in specific skill performance. 

PMID- 24688272
TI  - Creatine supplementation and exercise performance: a brief review.
AB  - During the past decade, the nutritional supplement creatine monohydrate has been
      gaining popularity exponentially. Introduced to the general public in the early
      1990s, shortly after the Barcelona Olympic Games, creatine (Cr) has become one of
      the most widely used nutritional supplements or ergogenic aids, with loading
      doses as high as 20-30 g.day(-1) for 5-7 days typical among athletes. This paper
      reviews the available research that has examined the potential ergogenic value of
      creatine supplementation (CrS) on exercise performance and training adaptations.
      Short-term CrS has been reported to improve maximal power/strength, work
      performed during sets of maximal effort muscle contractions, single-effort sprint
      performance, and work performed during repetitive sprint performance. During
      training CrS has been reported to promote significantly greater gains in
      strength, fat free mass, and exercise performance primarily of high intensity
      tasks. However, not all studies demonstrate a beneficial effect on exercise
      performance, as CrS does not appear to be effective in improving running and
      swimming performance. CrS appears to pose no serious health risks when taken at
      doses described in the literature and may enhance exercise performance in
      individuals that require maximal single effort and/or repetitive sprint bouts. 

PMID- 24688273
TI  - Heart rate during sleep: implications for monitoring training status.
AB  - Resting heart rate has sometimes been used as a marker of training status. It is
      reasonable to assume that the relationship between heart rate and training status
      should be more evident during sleep when extraneous factors that may influence
      heart rate are reduced. Therefore the aim of the study was to assess the
      repeatability of monitoring heart rate during sleep when training status remained
      unchanged, to determine if this measurement had sufficient precision to be used
      as a marker of training status. The heart rate of ten female subjects was
      monitored for 24 hours on three occasions over three weeks whilst training status
      remained unchanged. Average, minimum and maximum heart rate during sleep was
      calculated. The average heart rate of the group during sleep was similar on each
      of the three tests (65 +/- 9, 63 +/- 6 and 67 +/- 7 beats.min(-1) respectively).
      The range in minimum heart rate variation during sleep for all subjects over the
      three testing sessions was from 0 to 10 beats.min(-1) (mean = 5 +/- 3 beats.min(
      1)) and for maximum heart rate variation was 2 to 31 beats.min(-1) (mean = 13 +/-
      9 beats.min(-1)). In summary it was found that on an individual basis the minimum
      heart rate during sleep varied by about 8 beats.min(-1). This amount of intrinsic
      day-to-day variation needs to be considered when changes in heart rate that may
      occur with changes in training status are interpreted. 

PMID- 24688274
TI  - A new approach to modeling vertical stiffness in heel-toe distance runners.
AB  - Various models have been used to describe distance running technique. Among
      these, the mass-spring model is fairly simple to use and apply, but when employed
      as a model, does not predict vertical force accurately especially when a heel
      strike is exhibited. The purpose of this article is to demonstrate how the mass
      spring model can be modified to provide a simple, yet accurate prediction of
      ground reaction forces in distance running. Sixteen subjects ran on a force
      instrumented treadmill. Vertical forces during running at a self-selected pace
      were collected at 500 Hz. Vertical stiffness was calculated using the
      conventional mass-spring model with a constant stiffness and then a high-low
      method where stiffness was varied from a high to low value during the heel
      strike. Fishers z-test was used to compare correlations between predicted and
      measured ground reaction forces for each method of calculating stiffness. The
      high-low method of calculating stiffness provided a better fit of predicted to
      measured ground reaction forces than the constant stiffness method (p < 0.01).
      The high-low method of calculating stiffness avoids the difficulties of applying
      multiple masses, springs, or dampers while simply, yet accurately matching
      predicted to measured ground reaction forces. 

PMID- 24688275
TI  - Kinematic determinants of early acceleration in field sport athletes.
AB  - Acceleration performance is important for field sport athletes that require a
      high level of repeat sprint ability. Although acceleration is widely trained for,
      there is little evidence outlining which kinematic factors delineate between good
      and poor acceleration. The aim of this study was to investigate the kinematic
      differences between individuals with fast and slow acceleration. Twenty field
      sport athletes were tested for sprint ability over the first three steps of a 15m
      sprint. Subjects were filmed at high speed to determine a range of lower body
      kinematic measures. For data analysis, subjects were then divided into relatively
      fast (n = 10) and slow (n = 10) groups based on their horizontal velocity. Groups
      were then compared across kinematic measures, including stride length and
      frequency, to determine whether they accounted for observed differences in sprint
      velocity. The results showed the fast group had significantly lower (~11-13%)
      left and right foot contact times (p < .05), and an increased stride frequency
      (~9%), as compared to the slow group. Knee extension was also significantly
      different between groups (p < .05). There was no difference found in stride
      length. It was concluded that those subjects who are relatively fast in early
      acceleration achieve this through reduced ground contact times resulting in an
      improved stride frequency. Training for improved acceleration should be directed
      towards using coaching instructions and drills that specifically train such
      movement adaptations. 

PMID- 24688276
TI  - Can Aerobic and Anaerobic Power be Measured in a 60-Second Maximal Test?
AB  - The primary objective of this study was to assess the efficacy of measuring both
      aerobic and anaerobic power in a 60-second, maximal effort test. It was
      hypothesized that oxygen consumption increases rapidly during maximal effort and
      maximal oxygen consumption (VO2 max) may be reached in one minute. Fifteen United
      States Cycling Federation competitive cyclists performed the following tests: 1)
      practice 60-second maximal exertion test; 2) standard incremental workload VO2
      max test; 3) Wingate anaerobic power test (WAT); 4) VO2 measured during 60-second
      maximal exertion test (60-SEC); and 5) VO2 measured during 75-second maximal
      exertion test (75-SEC). All tests were performed on an electrically-braked cycle
      ergometer. Hydrostatic weighing was performed to determine percent body fat. Peak
      oxygen consumption values for the 60-SEC (53.4 ml.kg(-1).min(-1), 92% VO2 max),
      and 75-SEC (52.6 ml.kg(-1).min(-1), 91% VO2 max) tests were significantly lower
      than VO2 max (58.1 ml.kg(-1).min(-1)). During the 75-SEC test, there was no
      significant difference in percentage VO2max from 30 seconds to 75 seconds,
      demonstrating a plateau effect. There were no significant differences in peak
      power or relative peak power between the Wingate, 60-SEC, and 75 SEC tests while,
      as expected, mean power, relative mean power, and fatigue index were
      significantly different between these tests. Power measures were highly
      correlated among all three tests. It was concluded that VO2 max was not attained
      during either the 60-SEC nor 75-SEC tests. Furthermore, high correlations in
      power output for WAT, 60-SEC, and 75-SEC precludes the necessity for anaerobic
      tests longer than the 30-second WAT. 

PMID- 24688277
TI  - Effect of 30 degrees c heat on the anaerobic capacity of heat acclimatised
      athletes.
AB  - The main finding of this study was that for heat acclimatised athletes, there was
      no significant difference (p=0.58) in anaerobic capacity for temperate (21.8 +/-
      0.5  degrees C; 52 +/- 5 % relative humidity) compared with warm conditions (29.6
      +/- 0.5  degrees C; 51 +/- 9 % relative humidity). Anaerobic capacity was
      estimated using the maximal accumulated oxygen deficit (MAOD) during constant
      intensity cycling at 120% peak rate of O2 consumption until exhaustion. This
      yielded mean MAOD values of 3.3 +/- 0.9 and 3.5 +/- 1.1 L for temperate and warm
      conditions, respectively. Peak post-exercise lactate values of 14.7 +/- 3.8 and
      14.4 +/- 4.5 mmol.L(-1) for temperate and warm conditions respectively, were also
      not significantly different (p=0.72). Time to exhaustion (TTE) was similarly
      unchanged (p=0.56), being 175 +/- 19 and 170 +/- 18 s for temperate and warm
      conditions, respectively. These results suggest that the MAOD remains a valid
      test throughout environmental temperatures for the range of 20-30  degrees C when
      used with heat acclimatised athletes. 

PMID- 24688278
TI  - Glutamine Supplementation did not Benefit Athletes During Short-Term Weight
      Reduction.
AB  - The purpose was to determine if glutamine supplementation would prevent a loss of
      lean mass in athletes during a 12-day weight reduction program. It was
      hypothesized that supplementation would spare lean body mass. Subjects (n=18)
      exercised and dieted to create a 4186kJ.day(-1) energy deficit and a 8372 kJ.day(
      1) energy deficit on days 1-5, days 6-12, respectively. The glutamine (GLN) group
      (n=9) ingested 0.35 g.kg(-1) body mass of glutamine while a placebo was
      administered to the remaining subjects. Body mass (BM), lean body mass (LBM) and
      fat mass (FM), were measured at days 0, 6, and 12. GLN and placebo groups both
      lost significant amounts of BM, LBM and FM. There were no significant differences
      between groups. The findings indicate little benefit for retention of lean mass
      with supplementation of glutamine during a short-term weight reduction program. 

PMID- 24688279
TI  - Strategic priorities for increasing physical activity among adults age 50 and
      older: the national blueprint consensus conference summary report.
AB  - On May 1, 2001, a coalition of national organizations released a major planning
      document designed to develop a national strategy for the promotion of physically
      active lifestyles among the mid-life and older adult population. The National
      Blueprint: Increasing Physical Activity Among Adults Age 50 and Older was
      developed with input from 46 organizations with expertise in health, medicine,
      social and behavioral sciences, epidemiology, gerontology/geriatrics, clinical
      science, public policy, marketing, medical systems, community organization, and
      environmental issues. The Blueprint notes that, despite a wealth of evidence
      about the benefits of physical activity for mid-life and older persons, there has
      been little success in convincing age 50+ Americans to adopt physically active
      lifestyles. The Blueprint identifies barriers in the areas of research, home and
      community programs, medical systems, public policy and advocacy, and marketing
      and communications. In addition to identifying barriers, the Blueprint proposes a
      number of concrete strategies that could be employed in order to overcome the
      barriers to physical activity in society at large. This report summarizes the
      outcome of the National Blueprint Consensus Conference that was held in October
      2002. In this conference, representatives of more than 50 national organizations
      convened in Washington, D.C. with the goal of identifying high priority and high
      feasibility strategies which would advance the National Blueprint and which could
      be initiated within the next 12 to 24 months. Participants in the consensus
      conference were assigned to one of five breakout groups: home and community,
      marketing, medical systems, public policy, and research. Each breakout group was
      charged with identifying the three highest priority strategies within their area
      for effectively increasing physical activity levels in the mid-life and older
      adult population. In addition to the 15 strategies identified by the breakout
      groups, three "cross-cutting" strategies were added which were considered to be
      broad-based in scope and which applied to more than one of the breakout themes. A
      national organization was identified to take the lead in planning and
      implementing each strategy. A summary of the 18 strategies and lead organizations
      is presented. The National Blueprint Consensus Conference has identified an
      ambitious agenda of strategies and tactics that will need to be implemented in
      order to overcome societal barriers to physical activity among the mid-life and
      older adult population. More than 50 national organizations have expressed a
      commitment to work towards the implementation of the Blueprint agenda. Eighteen
      priority strategies have been identified in the areas of home and community,
      marketing, medical systems, public policy, and research. The organizations
      charged with the task of implementing the high priority strategies will use
      professional networks and established delivery channels and communication systems
      to translate this plan into action. 

PMID- 24688280
TI  - Bilateral os acromiale in a division I basketball player.
AB  - An unfused acromial epiphysis, called os acromiale, can become unstable and
      mobile when the deltoid contracts. This may cause pain and lead to impingement
      syndrome and rotator cuff tearing. After sustaining a direct blow to the right
      shoulder, a male division I basketball player was diagnosed with impingement
      syndrome and an os acromiale. Following failed conservative treatment, the
      athlete underwent arthroscopic subacromial decompression & debridement of the
      loose os acromiale in the right shoulder. One year later, following a fall on the
      left shoulder, the athlete was diagnosed with os acromiale, impingement syndrome
      and a superior labrum anterior-posterior (SLAP) lesion. Arthroscopic repair of
      the unstable type II SLAP lesion, together, with arthroscopic subacromial
      decompression, and resection of the os acromiale was performed on the left
      shoulder. Both surgeries were successful and the athlete was able to return to
      competition subsequent to completing a progressive shoulder rehabilitation
      program. Symptomatic os acromiale is rarely seen in young athletes. However,
      proper diagnosis and management is necessary for a successful recovery. Os
      acromiale should be considered as a part of the differential diagnosis in any
      athlete with rotator cuff impingement symptoms. 

PMID- 24688281
TI  - Great toe pain in a competitive tennis athlete.
AB  - As a variably occurring sesamoid, the hallucal interphalangeal sesamoid can
      significantly alter the biomechanics of the great toe. With modifications to the
      way the great toe functions, there are pathologies that inevitably arise. These
      pathologies can be quite serious and debilitating. While clinicians may take a
      conservative approach to treatment and focus on alleviating the symptoms, the
      physically active patient who desires to return to competitive participation may
      benefit most by having the source of the pathology removed altogether. The
      following is a report of an athlete who returned to competition six weeks after
      surgical excision of the anomalous hallucal interphalangeal sesamoid. 

PMID- 24688282
TI  - Level of achievement motivation of young tennis players and their future
      progress.

PMID- 24688283
TI  - Mimicking the nanostructure of bone matrix to regenerate bone.
AB  - Key features of bone tissue structure and composition are capable of directing
      cellular behavior towards the generation of new bone tissue. Bone tissue, as well
      as materials derived from bone, have a long and successful history of use as bone
      grafting materials. Recent developments in design and processing of synthetic
      scaffolding systems has allowed the replication of the bone's desirable
      biological activity in easy to fabricate polymeric materials with nano-scale
      features exposed on the surface. The biological response to these new tissue
      engineering scaffold materials oftentimes exceeds that seen on scaffolds produced
      using biological materials.

PMID- 24688284
TI  - Gestational diabetes mellitus (GDM) decreases butyrylcholinesterase (BChE)
      activity and changes its relationship with lipids.
AB  - Many conditions interfere with butyrylcholinesterase (BChE) activity, e.g.,
      pregnancy or presence of the BCHE gene variant -116A can decrease activity
      whereas obesity and types I and II diabetes mellitus can increase activity. In
      this study, we examined BChE activity, -116A and 1615A BCHE gene variants, and
      anthropometric and biochemical variables associated with diabetes in patients
      with gestational diabetes mellitus (GDM) and in healthy pregnant women. BChE
      activity was measured spectrophotometrically using propionylthiocholine as
      substrate and genotyping of the -116 and 1615 sites of the BCHE gene was done
      with a TaqMan SNP genotyping assay. Three groups were studied: 150 patients with
      GDM, 295 healthy pregnant women and 156 non-pregnant healthy women. Mean BChE
      activity was significantly lower in healthy pregnant women than in women from the
      general population and was further reduced in GDM patients. BChE activity was
      significantly reduced in carriers of -116A in GDM patients and healthy pregnant
      women. Although GDM patients had a significantly higher mean body mass index
      (BMI) and triglycerides than healthy pregnant women, they had lower mean BChE
      activity, suggesting that the lowering effect of GDM on BChE activity was
      stronger than the characteristic enhancing effect of increased BMI and
      triglycerides. 

PMID- 24688285
TI  - Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani
      population.
AB  - Polymorphisms in the regulatory region of the CCR5 gene affect protein expression
      and modulate the progress of HIV-1 disease. Because of this prominent role,
      variations in this gene have been under differential pressure and their
      frequencies vary among human populations. The CCR2V64I mutation is tightly linked
      to certain polymorphisms in the CCR5 gene. The current Omani population is
      genetically diverse, a reflection of their history as traders who ruled extensive
      regions around the Indian Ocean. In this study, we examined the CCR2-CCR5
      haplotypes in Omanis and compared the patterns of genetic diversity with those of
      other populations. Blood samples were collected from 115 Omani adults and genomic
      DNA was screened to identify the polymorphic sites in the CCR5 gene and the
      CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G
      showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5
      2135C both had a frequency of 36%. These alleles showed moderate levels of
      heterozygosity, indicating that they were under balancing selection. However, the
      well-known allele CCR5Delta32 was relatively rare. Eleven haplotypes were
      identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2
      (12%). 

PMID- 24688286
TI  - Obesity-related gene ADRB2, ADRB3 and GHRL polymorphisms and the response to a
      weight loss diet intervention in adult women.
AB  - The individual response to diet may be influenced by gene polymorphisms. This
      study hypothesized that ADRB2 (Gln27Glu, rs1042714 and Arg16Gly, rs1042713),
      ADRB3 (Trp64Arg, rs4994) and GHRL (Leu72Met, rs696217) polymorphisms moderate
      weight loss. The study was a seven weeks dietary weight loss intervention with
      Brazilian adult obese women (n = 109). The body mass index (BMI) was calculated
      and polymorphisms in these genes were assessed by real-time PCR assays. Two-way
      repeated-measures ANOVA (2 * 2) were used to analyze the intervention effect
      between polymorphisms and BMI over the period and after stratification for age
      and socioeconomic status (SES). The weight loss intervention resulted in
      decreased BMI over the seven-week period (p < 0.001), for high and low SES (p <
      0.05) and mainly for participants with 30-49 y. The intervention did not result
      in a statistically significant difference in weight loss between polymorphism
      carriers and non-carriers, and although, the ADRB2, ADRB3 and GHRL polymorphisms
      did not moderate weight loss, the Gln27Glu polymorphism carriers showed a lower
      BMI compared to non-carriers in the low SES (p = 0.018) and the 30-39 y (p =
      0.036) groups, suggesting a role for this polymorphism related to BMI control. 

PMID- 24688288
TI  - Scattered organization of the histone multigene family and transposable elements
      in Synbranchus.
AB  - The fish species Synbranchus marmoratus is widely distributed throughout the
      Neotropical region and exhibits a significant karyotype differentiation. However,
      data concerning the organization and location of the repetitive DNA sequences in
      the genomes of these karyomorphs are still lacking. In this study we made a
      physical mapping of the H3 and H4 histone multigene family and the transposable
      elements Rex1 and Rex3 in the genome of three known S. marmoratus karyomorphs.
      The results indicated that both histone sequences seem to be linked with one
      another and are scattered all over the chromosomes of the complement, with a
      little compartmentalization in one acrocentric pair, which is different from
      observations in other fish groups. Likewise, the transposable elements Rex1 and
      Rex3 were also dispersed throughout the genome as small clusters. The data also
      showed that the histone sites are organized in a differentiated manner in the
      genomes of S. marmoratus, while the transposable elements Rex1 and Rex3 do not
      seem to be compartmentalized in this group. 

PMID- 24688287
TI  - Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients
      followed within the MPS Brazil Network.
AB  - Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by
      deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect
      of enzyme replacement therapy (ERT) for this condition. We conducted an
      exploratory, open-label, non-randomized, multicenter cohort study of patients
      with MPS I. Data were collected from questionnaires completed by attending
      physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5
      years later (T2; n = 24/34). The 24 patients for whom data were available at T2
      were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months;
      6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4
      with severe phenotype). For all variables in which there was no between-group
      difference at baseline, a delta of >= +/- 20% was considered clinically relevant.
      The following clinically relevant differences were identified in group B in T2:
      lower rates of mortality and reported hospitalization for respiratory infection;
      lower frequency of hepatosplenomegaly; increased reported rates of obstructive
      sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity.
      These changes could be due to the effect of ERT or of other therapies which have
      also been found more frequently in group B. Our findings suggest MPS I patients
      on ERT also receive a better overall care. ERT may have a positive effect on
      respiratory morbidity and overall mortality in patients with MPS I. Additional
      studies focusing on these outcomes and on other therapies should be performed. 

PMID- 24688289
TI  - Genetic diversity and population structure of bocachico Prochilodus magdalenae
      (Pisces, Prochilodontidae) in the Magdalena River basin and its tributaries,
      Colombia.
AB  - Prochilodus magdalenae is an endemic freshwater fish that occurs in the
      Magdalena, Sinu and Atrato hydrographic basins. It has an important economic role
      and is a food resource for the artisanal fishing communities. Its socioeconomic
      importance contrasts with the current status of its fisheries, where stocks are
      being depleted. Considering its importance and lack of information on its genetic
      structure, we used seven microsatellite markers to assess the genetic structure
      of wild populations of P. magdalenae. The genetic diversity was assessed and the
      population genetic structure was estimated through Fst, analysis of molecular
      variance and Bayesian analysis. A total of 290 alleles were found in all loci
      throughout all population. The high polymorphism contrasts with the levels of
      observed heterozygosity (Ho = 0.276), which are the lowest values recorded for
      the family. We found three populations of bocachico coexisting throughout the
      studied system, contradicting the hypothesis that freshwater migratory fish form
      panmictic populations. These results on the genetic structure of P. magdalenae
      constitute tools for a better understanding of the behavior and biology of this
      species, contributing to fish management and conservation programs. 

PMID- 24688290
TI  - Chromosome mapping of repetitive sequences in four Serrasalmidae species
      (Characiformes).
AB  - The Serrasalmidae family is composed of a number of commercially interesting
      species, mainly in the Amazon region where most of these fishes occur. In the
      present study, we investigated the genomic organization of the 18S and 5S rDNA
      and telomeric sequences in mitotic chromosomes of four species from the basal
      clade of the Serrasalmidae family: Colossoma macropomum, Mylossoma aureum, M.
      duriventre, and Piaractus mesopotamicus, in order to understand the chromosomal
      evolution in the family. All the species studied had diploid numbers 2n = 54 and
      exclusively biarmed chromosomes, but variations of the karyotypic formulas were
      observed. C-banding resulted in similar patterns among the analyzed species, with
      heterochromatic blocks mainly present in centromeric regions. The 18S rDNA
      mapping of C. macropomum and P. mesopotamicus revealed multiple sites of this
      gene; 5S rDNA sites were detected in two chromosome pairs in all species,
      although not all of them were homeologs. Hybridization with a telomeric probe
      revealed signals in the terminal portions of chromosomes in all the species and
      an interstitial signal was observed in one pair of C. macropomum. 

PMID- 24688291
TI  - Validation of a microsatellite panel for parentage testing of locally adapted and
      commercial goats in Brazil.
AB  - Brazilian goats are generally kept in small herds and extensive rearing systems,
      mainly in the northeastern region of the country. Despite production improvement
      in recent years, the lack of pedigree control has affected genetic progress. This
      study aimed to validate a panel of 16 microsatellites for parentage testing in
      locally adapted and commercial goats breeds raised in Brazil, as well as to
      compare its efficiency with the panel recommended by the Brazilian Ministry of
      Agriculture, Livestock and Supplies (MAPA) in 2004. The number of alleles and
      expected heterozygosity (He) per marker ranged from four to 18, and from 0.051 to
      0.831, respectively. Using all markers, 100% of parentage cases of the validation
      dataset were resolved with a strict confidence level of 95%. The 16
      microsatellites panel showed adequate exclusion power (99.99%) and identity
      accuracy (99.99%). Suggestions for improvement of the marker panel endorsed by
      MAPA are provided. 

PMID- 24688292
TI  - The lowest diploid number in Testudines: Banding patterns, telomeric and 45S rDNA
      FISH in Peltocephalus dumerilianus, 2n = 26 and FN = 52 (Pleurodira,
      Podocnemididae).
AB  - The karyotype of the big-headed Amazon River turtle, Peltocephalus dumerilianus,
      is characterized based on a sample of seven juveniles from Reserva Biologica do
      Rio Trombetas, Para State, Brazil (1 degrees 30' S, 56 degrees 34' W). Here we
      present the first results on GTG and CBG-banding patterns, Ag-NOR staining and
      FISH, with telomeric and 45S rDNA sequences as probes. A cytogenetic comparison
      with related Podocnemidae is also provided. 

PMID- 24688293
TI  - Analysis of genetic population structure in Acacia caven (Leguminosae,
      Mimosoideae), comparing one exploratory and two Bayesian-model-based methods.
AB  - Bayesian clustering as implemented in STRUCTURE or GENELAND software is widely
      used to form genetic groups of populations or individuals. On the other hand, in
      order to satisfy the need for less computer-intensive approaches, multivariate
      analyses are specifically devoted to extracting information from large datasets.
      In this paper, we report the use of a dataset of AFLP markers belonging to 15
      sampling sites of Acacia caven for studying the genetic structure and comparing
      the consistency of three methods: STRUCTURE, GENELAND and DAPC. Of these methods,
      DAPC was the fastest one and showed accuracy in inferring the K number of
      populations (K = 12 using the find.clusters option and K = 15 with a priori
      information of populations). GENELAND in turn, provides information on the area
      of membership probabilities for individuals or populations in the space, when
      coordinates are specified (K = 12). STRUCTURE also inferred the number of K
      populations and the membership probabilities of individuals based on ancestry,
      presenting the result K = 11 without prior information of populations and K = 15
      using the LOCPRIOR option. Finally, in this work all three methods showed high
      consistency in estimating the population structure, inferring similar numbers of
      populations and the membership probabilities of individuals to each group, with a
      high correlation between each other. 

PMID- 24688294
TI  - TaWRKY68 responses to biotic stresses are revealed by the orthologous genes from
      major cereals.
AB  - WRKY transcription factors have been extensively characterized in the past 20
      years, but in wheat, studies on WRKY genes and their function are lagging behind
      many other species. To explore the function of wheat WRKY genes, we identified a
      TaWRKY68 gene from a common wheat cultivar. It encodes a protein comprising 313
      amino acids which harbors 19 conserved motifs or active sites. Gene expression
      patterns were determined by analyzing microarray data of TaWRKY68 in wheat and of
      orthologous genes from maize, rice and barley using Genevestigator. TaWRKY68
      orthologs were identified and clustered using DELTA-BLAST and COBALT programs
      available at NCBI. The results showed that these genes, which are expressed in
      all tissues tested, had relatively higher levels in the roots and were up
      regulated in response to biotic stresses. Bioinformatics results were confirmed
      by RT-PCR experiments using wheat plants infected by Agrobacterium tumefaciens
      and Blumeria graminis, or treated with Deoxynivalenol, a Fusarium graminearum
      induced mycotoxin in wheat or barley. In summary, TaWRKY68 functions differ
      during plant developmental stages and might be representing a hub gene function
      in wheat responses to various biotic stresses. It was also found that including
      data from major cereal genes in the bioinformatics analysis gave more accurate
      and comprehensive predictions of wheat gene functions. 

PMID- 24688295
TI  - Expression of stress-related genes in zebrawood (Astronium fraxinifolium,
      Anacardiaceae) seedlings following germination in microgravity.
AB  - Seeds of a tropical tree species from Brazil, Astronium fraxinifolium, or
      zebrawood, were germinated, for the first time in microgravity, aboard the
      International Space Station for nine days. Following three days of subsequent
      growth under normal terrestrial gravitational conditions, greater root length and
      numbers of secondary roots was observed in the microgravity-treated seedlings
      compared to terrestrially germinated controls. Suppression subtractive
      hybridization of cDNA and EST analysis were used to detect differential gene
      expression in the microgravity-treated seedlings in comparison to those initially
      grown in normal gravity (forward subtraction). Despite their return to, and
      growth in normal gravity, the subtracted library derived from microgravity
      treated seedlings was enriched in known microgravity stress-related ESTs,
      corresponding to large and small heat shock proteins, 14-3-3-like protein,
      polyubiquitin, and proteins involved in glutathione metabolism. In contrast, the
      reverse-subtracted library contained a comparatively greater variety of general
      metabolism-related ESTs, but was also enriched for peroxidase, possibly
      indicating the suppression of this protein in the microgravity-treated seedlings.
      Following continued growth for 30 days, higher concentrations of total
      chlorophyll were detected in the microgravity-exposed seedlings. 

PMID- 24688296
TI  - Effects of artichoke (Cynara scolymus) leaf and bloom head extracts on chemically
      induced DNA lesions in Drosophila melanogaster.
AB  - The genotoxicity of bloom head (BHE) and leaf (LE) extracts from artichoke
      (Cynara scolymus L.), and their ability to modulate the mutagenicity and
      recombinogenicity of two alkylating agents (ethyl methanesulfonate - EMS and
      mitomycin C - MMC) and the intercalating agent bleomycin (BLM), were examined
      using the somatic mutation and recombination test (SMART) in Drosophila
      melanogaster. Neither the mutagenicity nor the recombinogenicity of BLM or MMC
      was modified by co- or post-treatment with BHE or LE. In contrast, co-treatment
      with BHE significantly enhanced the EMS-induced genotoxicity involving mutagenic
      and/or recombinant events. Co-treatment with LE did not alter the genotoxicity of
      EMS whereas post-treatment with the highest dose of LE significantly increased
      this genotoxicity. This enhancement included a synergistic increase restricted to
      somatic recombination. These results show that artichoke extracts promote
      homologous recombination in proliferative cells of D. melanogaster. 

PMID- 24688297
TI  - Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine
      salt in three different organisms.
AB  - There is considerable controversy with regard to the genotoxicity of glyphosate,
      with some reports stating that this compound is non-toxic for fish, birds and
      mammals. In this work, we used the comet assay to examine the genotoxicity of
      glyphosate isopropylamine (0.7, 7, 70 and 700 MUM) in human lymphocytes,
      erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430)
      in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to
      5 mM N-nitrosodiethylamine (NDEA) were used as positive and negative controls,
      respectively. Significant (p < 0.01) genetic damage was observed in vivo and in
      vitro in all cell types and organisms tested. Human lymphocytes and Tradescantia
      hairs showed lower genetic damage in vivo compared to in vitro, possibly because
      of efficient metabolization of the herbicide. In O. niloticus erythrocytes,
      significant (p < 0.001) genotoxicity was observed at >= 7 MUM, whereas in vitro,
      glyphosphate was genotoxic in human lymphocytes and Tradescantia hairs at >= 0.7
      MUM. These results indicate that glyphosate is genotoxic in the cells and
      organisms studied at concentrations of 0.7-7 MUM. 

PMID- 24688298
TI  - Effects of beta-glucan polysaccharide revealed by the dominant lethal assay and
      micronucleus assays, and reproductive performance of male mice exposed to
      cyclophosphamide.
AB  - beta-glucan is a well-known polysaccharide for its chemopreventive effect. This
      study aimed to evaluate the chemopreventive ability of beta-glucan in somatic and
      germ cells through the dominant lethal and micronucleus assays, and its influence
      on the reproductive performance of male mice exposed to cyclophosphamide. The
      results indicate that beta-glucan is capable of preventing changes in DNA in both
      germ cells and somatic ones. Changes in germ cells were evaluated by the dominant
      lethal assay and showed damage reduction percentages of 46.46% and 43.79% for the
      doses of 100 and 150 mg/kg. For the somatic changes, evaluated by micronucleus
      assay in peripheral blood cells in the first week of treatment, damage reduction
      percentages from 80.63-116.32% were found. In the fifth and sixth weeks, the
      percentage ranged from 10.20-52.54% and -0.95-62.35%, respectively. Besides the
      chemopreventive efficiency it appears that the beta-glucan, when combined with
      cyclophosphamide, is able to improve the reproductive performance of males
      verified by the significant reduction in rates of post-implantation losses and
      reabsorption in the mating of nulliparous females with males treated with
      cyclophosphamide. 

PMID- 24688299
TI  - Use of the heteroduplex mobility assay and cell sorting to select genome
      sequences of the CCR5 gene in HEK 293T cells edited by transcription activator
      like effector nucleases.
AB  - Engineered nucleases such as zinc finger nucleases (ZFN) and transcription
      activator-like effector nucleases (TALEN) are one of the most promising tools for
      modifying genomes. These site-specific enzymes cause double-strand breaks that
      allow gene disruption or gene insertion, thereby facilitating genetic
      manipulation. The major problem associated with this approach is the labor
      intensive procedures required to screen and confirm the cellular modification by
      nucleases. In this work, we produced a TALEN that targets the human CCR5 gene and
      developed a heteroduplex mobility assay for HEK 293T cells to select positive
      colonies for sequencing. This approach provides a useful tool for the quick
      detection and easy assessment of nuclease activity. 

PMID- 24688300
TI  - bFGF promotes adipocyte differentiation in human mesenchymal stem cells derived
      from embryonic stem cells.
AB  - In this work we describe the establishment of mesenchymal stem cells (MSCs)
      derived from embryonic stem cells (ESCs) and the role of bFGF in adipocyte
      differentiation. The totipotency of ESCs and MSCs was assessed by
      immunofluorescence staining and RT-PCR of totipotency factors. MSCs were
      successfully used to induce osteoblasts, chondrocytes and adipocytes. MSCs that
      differentiated into adipocytes were stimulated with and without bFGF. The OD/DNA
      (optical density/content of total DNA) and expression levels of the specific
      adipocyte genes PPARgamma2 (peroxisome proliferator activated receptor gamma2)
      and C/EBPs were higher in bFGF cells. Embryonic bodies had a higher adipocyte
      level compared with cells cultured in plates. These findings indicate that bFGF
      promotes adipocyte differentiation. MSCs may be useful cells for seeding in
      tissue engineering and have enormous therapeutic potential for adipose tissue
      engineering. 

PMID- 24688301
TI  - The golden age of Drosophila research at the Universidade de Sao Paulo (USP): A
      testimonial on the decades 1940-1950.
AB  - This article is a testimonial written by the first author regarding the research
      work performed with Drosophila between 1943 and 1959, at the Departamento de
      Biologia Geral of the Universidade de Sao Paulo (USP), which permitted the
      building of a nucleus of excellence. This research work, focused on the
      systematics and population genetics of the Neotropical species, began during the
      first of Dobzhansky's six visits to USP. Special attention was given to the
      multinational megaprojects conducted during his longer stays, from August 1948 to
      July 1949 and from June 1955 to July 1956. The role played by the Rockefeller
      Foundation is duly remembered, and so is the undeniable contribution brought by
      Dobzhansky, to the establishment of several laboratories dedicated to research in
      the field of natural population genetics and to the qualification of human
      resources. On the other hand, important "backstage" episodes are retrieved which
      were omitted in the official history and occurred from the planning to the
      execution of the project, carried out on the Angra dos Reis islands. Special
      attention was given to the relationship problems which resulted from
      Dobzhansky's, the leader's, difficult personality and contributed to the failure
      of the second and last multinational project. 

PMID- 24688302
TI  - All human EF1alpha promoters are not equal: markedly affect gene expression in
      constructs from different sources.
AB  - The promoter is a major element in the expression cassette of gene therapy
      vectors. Optimal promoter selection can enhance target specificity and gene
      expression. Recently, we evaluated three different human elongation factor 1
      alpha (EF1alpha) promoters. The three promoters were put into the same expression
      vector, pAC-luc, driving expression of the luciferase cDNA. The activity from one
      EF1alpha promoter (termed EF1alpha -3), obtained in a commercial vector, was
      markedly lower when tested in vitro (from 50 - 500 x) in four cell lines and in
      vivo in rat submandibular glands (~250 x). Sequence differences in the EF1alpha 
      3 promoter likely account for the activity differences seen. Investigators need
      to recognize that all promoters of the same name may not be equivalent in driving
      transgene expression. 

PMID- 24688303
TI  - Dynamic response due to behind helmet blunt trauma measured with a human head
      surrogate.
AB  - A Human Head Surrogate has been developed for use in behind helmet blunt trauma
      experiments. This human head surrogate fills the void between Post-Mortem Human
      Subject testing (with biofidelity but handling restrictions) and commercial
      ballistic head forms (with no biofidelity but ease of use). This unique human
      head surrogate is based on refreshed human craniums and surrogate materials
      representing human head soft tissues such as the skin, dura, and brain. A
      methodology for refreshing the craniums is developed and verified through
      material testing. A test methodology utilizing these unique human head surrogates
      is also developed and then demonstrated in a series of experiments in which non
      perforating ballistic impact of combat helmets is performed with and without
      supplemental ceramic appliques for protecting against larger caliber threats.
      Sensors embedded in the human head surrogates allow for direct measurement of
      intracranial pressure, cranial strain, and head and helmet acceleration. Over
      seventy (70) fully instrumented experiments have been executed using this unique
      surrogate. Examples of the data collected are presented. Based on these series of
      tests, the Southwest Research Institute (SwRI) Human Head Surrogate has
      demonstrated great potential for providing insights in to injury mechanics
      resulting from non-perforating ballistic impact on combat helmets, and directly
      supports behind helmet blunt trauma studies. 

PMID- 24688304
TI  - Neural cell apoptosis induced by microwave exposure through mitochondria
      dependent caspase-3 pathway.
AB  - To determine whether microwave (MW) radiation induces neural cell apoptosis,
      differentiated PC12 cells and Wistar rats were exposed to 2.856 GHz for 5 min and
      15 min, respectively, at an average power density of 30  mW/cm2. JC-1 and TUNEL
      staining detected significant apoptotic events, such as the loss of mitochondria
      membrane potential and DNA fragmentation, respectively. Transmission electron
      microscopy and Hoechst staining were used to observe chromatin ultrastructure and
      apoptotic body formation. Annexin V-FITC/PI double staining was used to quantify
      the level of apoptosis. The expressions of Bax, Bcl-2, cytochrome c, cleaved
      caspase-3 and PARP were examined by immunoblotting or immunocytochemistry.
      Caspase-3 activity was measured using an enzyme-linked immunosorbent assay. The
      results showed chromatin condensation and apoptotic body formation in neural
      cells 6h after microwave exposure. Moreover, the mitochondria membrane potential
      decreased, DNA fragmentation increased, leading to an increase in the apoptotic
      cell percentage. Furthermore, the ratio of Bax/Bcl-2, expression of cytochrome c,
      cleaved caspase-3 and PARP all increased. In conclusion, microwave radiation
      induced neural cell apoptosis via the classical mitochondria-dependent caspase-3
      pathway. This study may provide the experimental basis for further investigation
      of the mechanism of the neurological effects induced by microwave radiation.

PMID- 24688305
TI  - Discrepancy between serological and virological analysis of viral hepatitis in
      hemodialysis patients.
AB  - BACKGROUND AND AIM: Viral hepatitis is a health threat for hemodialysis (HD)
      patients and it may be transmitted during treatment. Some patients categorized to
      have viral hepatitis were found to be non-viremic. To clarify the discrepancy
      between the serological tests in HD patients, we conducted the study. METHODS: A
      total of 1681 HD patients was included. Blood samples were analyzed for hepatitis
      B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV). Detection of
      hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were performed in
      either HBsAg (+) or anti-HCV (+) samples. HBV DNA/HCV RNA was also measured in a
      subset of HBsAg (-) and anti-HCV (-) patients. Liver function tests were analyzed
      and compared with the serological and virological tests. RESULTS: The serological
      tests showed that 230 patients (13.7%) were HBsAg (+) and 290 (17.3%) were anti
      HCV (+). We were unable to detect HBV DNA in 97 of 230 (42.2%) HBsAg (+)
      patients, and HCV RNA could not be found in 76 of 290 (26.2%) anti-HCV (+)
      patients. In 167 HBsAg (-) patients, only one showed a trace amount of HBV DNA.
      None of 151 anti-HCV (-) patients showed detectable HCV RNA. The prevalence rate
      of viral hepatitis remains high in Taiwanese HD patients: 13.7% for HBV and 17.3%
      for HCV. However, virological analysis showed 42.2% non-viremic rate for HBsAg
      and 26.2% non-viremic rate for anti-HCV. CONCLUSIONS: The findings might
      challenge the presently suggested principles of bed and machine dedication and
      the diagnosis of viral hepatitis in HD patients.

PMID- 24688306
TI  - Medical supplies shortages and burnout among greek health care workers during
      economic crisis: a pilot study.
AB  - Greece has been seriously affected by the economic crisis. In 2011 there were
      reports of 40% reduction to public hospital budgets. Occasional shortages of
      medical supplies have been reported in mass media. We attempted to pivotally
      investigate the frequency of medical supplies shortages in two Greek hospital
      units of the National Health System and to also assess their possible impact on
      burnout risk of health care workers. We conducted a cross-sectional study (n=303)
      of health care workers in two Greek hospitals who were present at the workplace
      during a casually selected working day (morning shift work). The Maslach Burnout
      Inventory (MBI) was used as the measure of burnout. An additional questionnaire
      was used about demographics, and working conditions (duration of employment,
      cumulative night shifts, type of hospital including medical supplies shortages
      and their impact on quality of healthcare. The prevalence of emotional
      exhaustion, depersonalization and low personal accomplishment was 44.5%, 43.2%
      and 51.5%, respectively. Medical supply shortages were significantly associated
      with emotional exhaustion and depersonalization. This finding provides
      preliminary evidence that austerity has affected health care in Greece. Moreover,
      the medical supply shortages in Greek hospitals may reflect the unfolding
      humanitarian crisis of the country. 

PMID- 24688307
TI  - Effect of chronic administration of forskolin on glycemia and oxidative stress in
      rats with and without experimental diabetes.
AB  - Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin
      activates adenylate cyclase, which increases intracellular cAMP levels. The
      antioxidant and antiinflammatory action of forskolin is due to inhibition of
      macrophage activation with a subsequent reduction in thromboxane B2 and
      superoxide levels. These characteristics have made forskolin an effective
      medication for heart disease, hypertension, diabetes, and asthma. Here, we
      evaluated the effects of chronic forskolin administration on blood glucose and
      oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes
      compared to 8 healthy male Wistar rats. Rats were treated with forskolin,
      delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood
      glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in
      healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine
      (8-OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting
      blood glucose was significantly higher at the end than at the beginning of the
      experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment
      lowered the fasting glucose at the end of the experiment but no effect was found
      on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in
      forskolin-treated than in untreated group. Our results showed that chronic
      administration of forskolin decreased fasting blood glucose levels; however, the
      reductions of 8-OHdG were not statistically significant. 

PMID- 24688308
TI  - Increased levels of circulating advanced glycation end-products in menopausal
      women with osteoporosis.
AB  - BACKGROUND: Advanced glycation end-products (AGEs) can accumulate in organs and
      tissues during ageing and diabetes. Increased levels of AGEs are found in the
      bone tissue of patients with osteoporosis. The purpose of this study was to
      evaluate circulating AGEs in patients with osteoporosis. METHODS: We evaluated
      plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal
      women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43
      healthy women without osteoporosis or osteopenia. RESULTS: Higher levels of serum
      AGEs were found in the osteoporosis or osteopenia group compared to healthy women
      (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar
      spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar
      spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12
      U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a
      3.31-fold risk of osteopenia regarding the hip T-score. CONCLUSION: Serum AGEs
      could be used to monitor the severity and progression of osteoporosis. An
      increased serum level of AGEs was associated with impaired bone formation and was
      a risk factor for the development of osteoporosis. Targeting AGEs may represent a
      novel therapeutic approach for primary or secondary osteoporosis.

PMID- 24688309
TI  - Commonality of drug-associated adverse events detected by 4 commonly used data
      mining algorithms.
AB  - OBJECTIVES: Data mining algorithms have been developed for the quantitative
      detection of drug-associated adverse events (signals) from a large database on
      spontaneously reported adverse events. In the present study, the commonality of
      signals detected by 4 commonly used data mining algorithms was examined. METHODS:
      A total of 2,231,029 reports were retrieved from the public release of the US
      Food and Drug Administration Adverse Event Reporting System database between 2004
      and 2009. The deletion of duplicated submissions and revision of arbitrary drug
      names resulted in a reduction in the number of reports to 1,644,220. Associations
      with adverse events were analyzed for 16 unrelated drugs, using the proportional
      reporting ratio (PRR), reporting odds ratio (ROR), information component (IC),
      and empirical Bayes geometric mean (EBGM). RESULTS: All EBGM-based signals were
      included in the PRR-based signals as well as IC- or ROR-based ones, and PRR- and
      IC-based signals were included in ROR-based ones. The PRR scores of PRR-based
      signals were significantly larger for 15 of 16 drugs when adverse events were
      also detected as signals by the EBGM method, as were the IC scores of IC-based
      signals for all drugs; however, no such effect was observed in the ROR scores of
      ROR-based signals. CONCLUSIONS: The EBGM method was the most conservative among
      the 4 methods examined, which suggested its better suitability for
      pharmacoepidemiological studies. Further examinations should be performed on the
      reproducibility of clinical observations, especially for EBGM-based signals.

PMID- 24688310
TI  - Trend analysis of primary midwife-led delivery care at a Japanese perinatal
      center.
AB  - OBJECTIVE: To perform trend analysis of primary midwife-led delivery care for
      'low risk' pregnant women at our hospital. METHODS: A retrospective cohort study
      was performed to examine trends and outcomes of labor under primary midwife-led
      delivery care at the Japanese Red Cross Katsushika Maternity Hospital between
      2008 and 2012. RESULTS: During the study period, the rate of deliveries initially
      considered 'low risk' decreased from 25 to 22% (p < 0.01). This change was
      associated with increased cases of previous Cesarean deliveries and preterm
      delivery. There were no significant changes in the neonatal outcomes; however,
      the rate of Cesarean delivery and incidence of severe perineal laceration in
      primary midwife-led delivery care were decreased from 2.1 and 3.3% to 0.3 (p =
      0.02) and 1.1% (p = 0.04), respectively due to the close cooperation between
      midwives and obstetricians. CONCLUSION: The rate of deliveries initially
      considered 'low risk' decreased over the last 5-year period. Closer cooperation
      between midwives and obstetricians is important in primary midwife-led delivery
      care.

PMID- 24688311
TI  - Sex-specific association of the zinc finger protein 259 rs2075290 polymorphism
      and serum lipid levels.
AB  - BACKGROUND: Little is known about the association of ZNF259 rs2075290 single
      nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population.
      This study aimed to detect the association of ZNF259 rs2075290 SNP and
      environmental factors with serum lipid levels between males and females in the
      Mulao and Han populations. METHODS AND RESULTS: Genotyping of ZNF259 rs2075290
      SNP was performed in 788 of Mulao and 778 of Han participants using polymerase
      chain reaction and restriction fragment length polymorphism. The genotype
      frequencies were significantly different between Mulao and Han populations (AA,
      50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han
      males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P =
      0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol
      (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were
      different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C
      and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and
      ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes
      (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male
      gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05
      0.01) but not in Mulao's. CONCLUSIONS: The subjects with AG/GG genotype in Mulao
      males and females and Han females have less favorable lipid profiles than those
      with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have
      more favorable lipid profiles than those with AA genotype. These findings suggest
      that the association between ZNF259 rs2075290 SNP and serum lipid levels might
      have ethnic- and/or sex-specificity.

PMID- 24688313
TI  - Identifying hedgehog signaling specific microRNAs in glioblastomas.
AB  - Aberrant activation of hedgehog (Hh) signaling pathway plays an important role in
      the development and proliferation of glioblastoma (GBM) cells. However, its
      mechanism remains unknown. MicroRNAs (miRNAs) are short non-coding RNA molecules
      which are involved in the post-transcriptional regulation of genes, and enrolled
      in signaling transduction network in tumors. This study was designed to
      investigate the role of miRNAs targeting the Hh signaling pathway in GBMs.
      According to the expression level of Gli1 mRNA measured by real time PCR, GBM
      samples were assigned to Gli1 high or low expression group. MiRNA microarray was
      applied to screen the dysregulated miRNA. As a result, 17 miRNAs were
      differentially expressed between Gli1 high expression and low expression groups
      (p < 0.005). Thirteen miRNAs including miR-125b-1 were downregulated, while only
      4 miRNAs including miR-144 were upregulated in Gli1 high expression group. In
      summary, our study presents a subset of miRNAs which target the Hh signaling
      pathway in GBMs, and throws some light on the aberrant activation mechanism. 

PMID- 24688312
TI  - A cell-based pharmacokinetics assay for evaluating tubulin-binding drugs.
AB  - Increasing evidence reveals that traditional pharmacokinetics parameters based on
      plasma drug concentrations are insufficient to reliably demonstrate accurate
      pharmacological effects of drugs in target organs or cells in vivo. This
      underscores the increasing need to improve the types and qualities of cellular
      pharmacokinetic information for drug preclinical screening and clinical efficacy
      assessments. Here we report a whole cell-based method to assess drugs that
      disturb microtubule dynamics to better understand different formulation-mediated
      intracellular drug release profiles. As proof of concept for this approach, we
      compared the well-known taxane class of anti-microtubule drugs based on
      paclitaxel (PTX), including clinically familiar albumin nanoparticle-based
      AbraxaneTM, and a polymer nanoparticle-based degradable paclitaxel carrier,
      poly(L-glutamic acid)-paclitaxel conjugate (PGA-PTX, also known as CT-2103)
      versus control PTX. This in vitro cell-based evaluation of PTX efficacy includes
      determining the cellular kinetics of tubulin polymerization, relative populations
      of cells under G2 mitotic arrest, cell proliferation and total cell viability.
      For these taxane tubulin-binding compounds, the kinetics of cell microtubule
      stabilization directly correlate with G2 arrest and cell proliferation,
      reflecting the kinetics and amounts of intracellular PTX release. Each individual
      cell-based dose-response experiment correlates with published, key therapeutic
      parameters and taken together, provide a comprehensive understanding of drug
      intracellular pharmacokinetics at both cellular and molecular levels. This whole
      cell-based evaluating method is convenient, quantitative and cost-effective for
      evaluating new formulations designed to optimize cellular pharmacokinetics for
      drugs perturbing tubulin polymerization as well as assisting in explaining drug
      mechanisms of action at cellular levels. 

PMID- 24688314
TI  - Comparison of methods for the extraction of DNA from formalin-fixed, paraffin
      embedded archival tissues.
AB  - AIM: Discussing a protocol involving xylene-ethanol deparaffinization on slides
      followed by a kit-based extraction that allows for the extraction of high quality
      DNA from FFPE tissues. METHODS: DNA was extracted from the FFPE tissues of 16
      randomly selected blocks. Methods involving deparaffinization on slides or tubes,
      enzyme digestion overnight or for 72 hours and isolation using phenol chloroform
      method or a silica-based commercial kit were compared in terms of yields,
      concentrations and the amplifiability. RESULTS: The highest yield of DNA was
      produced from the samples that were deparaffinized on slides, digested for 72
      hours and isolated with a commercial kit. Samples isolated with the phenol
      chloroform method produced DNA of lower purity than the samples that were
      purified with kit. The samples isolated with the commercial kit resulted in
      better PCR amplification. CONCLUSION: Silica-based commercial kits and
      deparaffinized on slides should be considered for DNA extraction from FFPE.

PMID- 24688315
TI  - Differential expression profile of long non-coding RNAs during differentiation of
      cardiomyocytes.
AB  - Many long non-coding RNAs (lncRNAs) are species specific and seem to be less
      conserved than protein-coding genes. Some of them are involved in the development
      of the lateral mesoderm in the heart and in the differentiation of
      cardiomyocytes. The purpose of the study was to investigate the expression
      profiles of lncRNAs during the differentiation of P19 cells into cardiomyocytes,
      with a view to studying the biological function of lncRNAs and their involvement
      in the mechanism of heart development. First, we observed the morphology of P19
      cells during differentiation using an inverted microscope. Then, cardiac troponin
      T (cTnT) expression was detected to validate that the cells had successfully
      differentiated into cardiac myocytes by real-time reverse transcriptase
      polymerase chain reaction (real-time RT-PCR) and western blotting. Lastly, the
      expression profile of lncRNA genes was obtained using an lncRNA microarray and
      real-time RT-PCR analyses. The microarray results showed that 40 lncRNAs were
      differentially expressed, of which 28 were upregulated and 12 were downregulated
      in differentiated cardiomyocytes. The differentially expressed lncRNAs were
      further validated. Our results illustrated a critical role of lncRNAs during the
      differentiation of P19 cells into cardiac myocytes, which will provide the
      foundation for further study of the biological functions of lncRNAs and the
      mechanism of heart development. 

PMID- 24688316
TI  - Tuberculosis disease diagnosis using artificial immune recognition system.
AB  - BACKGROUND: There is a high risk of tuberculosis (TB) disease diagnosis among
      conventional methods. OBJECTIVES: This study is aimed at diagnosing TB using
      hybrid machine learning approaches. MATERIALS AND METHODS: Patient epicrisis
      reports obtained from the Pasteur Laboratory in the north of Iran were used. All
      175 samples have twenty features. The features are classified based on
      incorporating a fuzzy logic controller and artificial immune recognition system.
      The features are normalized through a fuzzy rule based on a labeling system. The
      labeled features are categorized into normal and tuberculosis classes using the
      Artificial Immune Recognition Algorithm. RESULTS: Overall, the highest
      classification accuracy reached was for the 0.8 learning rate (alpha) values. The
      artificial immune recognition system (AIRS) classification approaches using fuzzy
      logic also yielded better diagnosis results in terms of detection accuracy
      compared to other empirical methods. Classification accuracy was 99.14%,
      sensitivity 87.00%, and specificity 86.12%.

PMID- 24688317
TI  - Serum hyperglycemia might be not related to fat composition of diet and vegetable
      composition of diet might improve sugar control in taiwanese diabetic subjects.
AB  - OBJECTIVE: This is an Asian study, which was designed to examine the correlations
      between biochemical data and food composition of diabetic patients in Taiwan.
      METHODS: One hundred and seventy Taiwanese diabetic patients were enrolled. The
      correlations between biochemical data and diet composition (from 24-hour recall
      of intake food) of these patients were explored (Spearman correlation, p < 0.05).
      Diet components were also correlated with each other to show diet characteristics
      of diabetic patients in Taiwan. Linear regression was also performed for the
      significantly correlated groups to estimate possible impacts from diet
      composition to biochemical data. RESULTS: Postprandial serum glucose level was
      negatively correlated with fat percentage of diet, intake amount of
      polyunsaturated fatty acid and fiber diet composition. Hemoglobin A1c was
      negatively correlated with fat diet, polyunsaturated fatty acid and vegetable
      diet. Fat composition, calorie percentage accounted by polyunsaturated fatty acid
      and monounsaturated fatty acid in diet seemed to be negatively correlated with
      sugar percentage of diet and positively correlated with vegetable and fiber
      composition of diet. Linear regression showed that intake amount of
      polyunsaturated fatty acid, calorie percentage accounted by polyunsaturated fatty
      acid, fat percentage of diet, vegetable composition of diet would predict lower
      hemoglobin A1c and postprandial blood sugar. Besides, higher percentage of fat
      diet composition could predict higher percentage of vegetable diet composition in
      Taiwanese diabetic patients. CONCLUSION: Fat diet might not elevate serum
      glucose. Vegetable diet and polyunsaturated fatty acid diet composition might be
      correlated with better sugar control in Taiwanese diabetic patients.

PMID- 24688318
TI  - Association study of ARL15 and CDH13 with T2DM in a Han Chinese population.
AB  - Several studies indicate that plasma adiponectin levels are associated with the
      risk of type 2 diabetes mellitus (T2DM) or T2DM risk factors in diverse
      populations. In addition to the adiponectin gene, several other genes have been
      postulated to influence plasma adiponectin levels. In this study, we investigated
      two single nucleotide polymorphisms (SNPs), rs4311394 and rs4783244, located
      intronically in the ADP-ribosylation factor-like protein 15 (ARL15) and the T
      cadherin (CDH13) genes, respectively. These SNPs were detected in a Han Chinese
      population using a TaqMan assay and evaluated for association with T2DM as well
      as with individual metabolic traits. Allele frequencies for rs4311394 were
      significantly different in T2DM and nondiabetes (NDM) groups (chi2 = 4.49, P =
      0.034). However, neither allele nor genotype frequencies for rs4783244 were
      associated with T2DM (chi2 = 0.33, P = 0.56 and chi2 = 2.35, P = 0.31
      respectively). The SNPs did not exhibit significant association with individual
      metabolic traits in the T2DM and NDM groups. Our results indicated that the G
      allele of the rs4311394 might be a susceptibility factor for T2DM in the Han
      Chinese population (odds ratio: 1.20; 95% confidence interval: 1.01-1.41). 

PMID- 24688319
TI  - C-terminal protein characterization by mass spectrometry: isolation of C-terminal
      fragments from cyanogen bromide-cleaved protein.
AB  - A sample preparation method for protein C-terminal peptide isolation from
      cyanogen bromide (CNBr) digests has been developed. In this strategy, the analyte
      was reduced and carboxyamidomethylated, followed by CNBr cleavage in a one-pot
      reaction scheme. The digest was then adsorbed on ZipTipC18 pipette tips for
      conjugation of the homoserine lactone-terminated peptides with 2,2'-dithiobis
      (ethylamine) dihydrochloride, followed by reductive release of 2-aminoethanethiol
      from the derivatives. The thiol-functionalized internal and N-terminal peptides
      were scavenged on activated thiol sepharose, leaving the C-terminal peptide in
      the flow-through fraction. The use of reversed-phase supports as a venue for
      peptide derivatization enabled facile optimization of the individual reaction
      steps for throughput and completeness of reaction. Reagents were replaced
      directly on the support, allowing the reactions to proceed at minimal sample
      loss. By this sequence of solid-phase reactions, the C-terminal peptide could be
      recognized uniquely in mass spectra of unfractionated digests by its unaltered
      mass signature. The use of the sample preparation method was demonstrated with
      low-level amounts of a whole, intact model protein. The C-terminal fragments were
      retrieved selectively and efficiently from the affinity support. The use of
      covalent chromatography for C-terminal peptide purification enabled recovery of
      the depleted material for further chemical and/or enzymatic manipulation. The
      sample preparation method provides for robustness and simplicity of operation and
      is anticipated to be expanded to gel-separated proteins and in a scaled-up format
      to high-throughput protein profiling in complex biological mixtures. 

PMID- 24688321
TI  - Calibration of wide-field deconvolution microscopy for quantitative fluorescence
      imaging.
AB  - Deconvolution enhances contrast in fluorescence microscopy images, especially in
      low-contrast, high-background wide-field microscope images, improving
      characterization of features within the sample. Deconvolution can also be
      combined with other imaging modalities, such as confocal microscopy, and most
      software programs seek to improve resolution as well as contrast. Quantitative
      image analyses require instrument calibration and with deconvolution, necessitate
      that this process itself preserves the relative quantitative relationships
      between fluorescence intensities. To ensure that the quantitative nature of the
      data remains unaltered, deconvolution algorithms need to be tested thoroughly.
      This study investigated whether the deconvolution algorithms in AutoQuant X3
      preserve relative quantitative intensity data. InSpeck Green calibration
      microspheres were prepared for imaging, z-stacks were collected using a wide
      field microscope, and the images were deconvolved using the iterative
      deconvolution algorithms with default settings. Afterwards, the mean intensities
      and volumes of microspheres in the original and the deconvolved images were
      measured. Deconvolved data sets showed higher average microsphere intensities and
      smaller volumes than the original wide-field data sets. In original and
      deconvolved data sets, intensity means showed linear relationships with the
      relative microsphere intensities given by the manufacturer. Importantly, upon
      normalization, the trend lines were found to have similar slopes. In original and
      deconvolved images, the volumes of the microspheres were quite uniform for all
      relative microsphere intensities. We were able to show that AutoQuant X3
      deconvolution software data are quantitative. In general, the protocol presented
      can be used to calibrate any fluorescence microscope or image processing and
      analysis procedure. 

PMID- 24688320
TI  - N-terminal protein characterization by mass spectrometry after cyanogen bromide
      cleavage using combined microscale liquid- and solid-phase derivatization.
AB  - A sample preparation method for protein N-terminal peptide isolation from
      cyanogen bromide (CNBr) protein digests has been developed. In this strategy, the
      CNBr cleavage was preceded by protein alpha- and epsilon-amine acetylation and
      carboxyamidomethylation in a one-pot reaction scheme. The peptide mixture was
      adsorbed on ZipTipC18 pipette tips for reaction of the newly generated N-termini
      with sulfosuccinimidyl-2-(biotinamido) ethyl-1, 3-dithiopropionate. In the
      subsequent steps, the peptides were exposed in situ to hydroxylamine for reversal
      of potential hydroxyl group acylation, followed by reductive release of the
      disulfide-linked biotinamido moiety from the derivatives. The selectively thiol
      group-functionalized internal and C-terminal peptides were reversibly captured by
      covalent chromatography on activated thiol-sepharose, leaving the N-terminal
      fragment in the flow-through fraction. The use of the reversed-phase support as a
      venue for postcleavage serial modification proved instrumental to ensure
      throughput and completeness of derivatization. By this sequence of solid-phase
      reactions, the N-terminal peptide could be recognized uniquely in the MALDI-mass
      spectra of unfractionated digests by its unaltered mass signature. The use of the
      sample preparation method was demonstrated with low-picomole amounts of model
      protein. The N-terminal CNBr fragments were retrieved selectively from the
      affinity support. The sample preparation method provides for robustness and
      simplicity of operation using standard equipment available in most biological
      laboratories and is anticipated to be readily expanded to gel-separated proteins.

PMID- 24688324
TI  - Advancing evidence-based practice - a quarterly compilation of research updates
      most likely to change clinical practice.

PMID- 24688323
TI  - From the Editor's Desk.

PMID- 24688325
TI  - Bioethics in Practice - A Quarterly Column About Medical Ethics: MOMS, Moms, and
      Their Babies.

PMID- 24688326
TI  - Clinical images - a quarterly column: chance fracture of the lumbar spine.

PMID- 24688327
TI  - Editorial - colorectal cancer.

PMID- 24688328
TI  - Surgical treatment for adult spinal deformity: projected cost effectiveness at 5
      year follow-up.
AB  - BACKGROUND: In the United States, expenditures related to spine care are
      estimated to account for $86 billion annually. Policy makers have set a cost
      effectiveness benchmark of less than $100,000/quality adjusted life year (QALY),
      forcing surgeons to defend their choices economically. This study projects the
      cost/QALY for surgical treatment of adult spinal deformity at 5-year follow-up
      based on 2-year cost- and health-related quality-of-life (HRQOL) data. METHODS:
      In a review of 541 patients with adult spinal deformity, the patients who
      underwent revision or were likely to undergo revision were identified and cost of
      surgery was doubled to account for the second procedure; all other patients
      maintained the cost of the initial surgery. Oswestry Disability Index (ODI) was
      modeled by revision status based on literature findings. Total surgical cost was
      based on Medicare reimbursement. Chi square and student t tests were utilized to
      compare cost-effective and non-cost-effective patients. RESULTS: The average
      cost/QALY at 5-year follow-up was $120,311.73. A total of 40.7% of patients fell
      under the threshold of a cost/QALY <$100,000. Cost-effective patients had higher
      baseline ODI scores (45% vs 34% [P=0.001]), lower baseline total Scoliosis
      Research Society scores (2.89 vs 3.00 [P=0.04]), and shorter fusions (8.23 vs
      9.87 [P=0.0001]). CONCLUSION: We found 40.7% of patients to be below the
      threshold of cost effectiveness. Factors associated with reaching the threshold
      <$100,000/QALY were greater preoperative disability, diagnosis of idiopathic
      scoliosis, poor preoperative HRQOL scores, and fewer fusion levels.

PMID- 24688329
TI  - Lateral lumbar interbody fusion for the correction of spondylolisthesis and adult
      degenerative scoliosis in high-risk patients: early radiographic results and
      complications.
AB  - BACKGROUND: Lateral lumbar interbody fusion (LLIF) is not associated with many of
      the complications seen in other interbody fusion techniques. This study used
      computed tomography (CT) scans, the radiographic gold standard, to assess
      interbody fusion rates achieved utilizing the LLIF technique in high-risk
      patients. METHODS: We performed a retrospective review of patients who underwent
      LLIF between January 2008 and July 2013. Forty-nine patients underwent nonstaged
      or staged LLIF on 119 levels with posterior correction and augmentation. Per
      protocol, patients received CT scans at their 1-year follow-up. Of the 49
      patients, 21 patients with LLIF intervention on 54 levels met inclusion criteria.
      Two board-certified musculoskeletal radiologists and the senior surgeon (JZ)
      assessed fusion. RESULTS: Of the 21 patients, 6 patients had had previous lumbar
      surgery, and the cohort's comorbidities included osteoporosis, diabetes, obesity,
      and smoking, among others. Postoperative complications occurred in 12 (57.1%)
      patients and included anterior thigh pain and weakness in 6 patients, all of
      which resolved by 6 months. Two cases of proximal junctional kyphosis occurred,
      along with 1 case of hardware pullout. Two cases of abdominal atonia occurred. By
      CT scan assessment, each radiologist found fusion was achieved in 53 of 54 levels
      (98%). The radiologists' findings were in agreement with the senior surgeon.
      CONCLUSION: Several studies have evaluated LLIF fusion and reported fusion rates
      between 88%-96%. Our results demonstrate high fusion rates using this technique,
      despite multiple comorbidities in the patient population. Spanning the ring
      apophysis with large LLIF cages along with supplemental posterior pedicle screw
      augmentation can enhance stability of the fusion segment and increase fusion
      rates.

PMID- 24688330
TI  - Minimally invasive versus open transforaminal lumbar interbody fusion for
      degenerative spondylolisthesis grades 1-2: patient-reported clinical outcomes and
      cost-utility analysis.
AB  - BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) is the standard
      surgical treatment for patients with lumbar degenerative spondylolisthesis who do
      not respond to a 6-week course of conservative therapy. A number of morbidities
      are associated with the conventional open-TLIF method, so minimally invasive
      surgery (MIS) techniques for TLIF (MIS-TLIF) have been introduced to reduce the
      trauma to paraspinal muscles and hasten postoperative recovery. Because providing
      cost-effective medical treatment is a core initiative of healthcare reforms, a
      comparison of open-TLIF and MIS-TLIF must include a cost-utility analysis in
      addition to an analysis of clinical effectiveness. METHODS: We compared patient
      reported clinical functional outcomes and hospital direct costs in age-matched
      patients treated surgically with either open-TLIF or MIS-TLIF. Patients were
      followed for at least 1 year, and patient scores on the Oswestry Disability Index
      (ODI) and visual analog scale (VAS) were analyzed at 6 weeks, 6 months, and >=1
      year postoperatively in the 2 treatment groups. RESULTS: Compared to their
      preoperative scores, patients in both the open-TLIF and MIS-TLIF groups had
      significant improvements in the ODI and VAS scores at each follow-up point, but
      no significant difference in functional outcome occurred between the open-TLIF
      and MIS-TLIF groups (P=0.46). However, open-TLIF is significantly more costly
      compared to MIS-TLIF (P=0.0002). CONCLUSION: MIS-TLIF is a more cost-effective
      treatment than open-TLIF for patients with degenerative spondylolisthesis and is
      equally effective as the conventional open-TLIF procedure, although further
      financial analysis-including an analysis of indirect costs-is needed to better
      understand the full benefit of MIS-TLIF.

PMID- 24688331
TI  - Minimally invasive laminectomy in spondylolisthetic lumbar stenosis.
AB  - BACKGROUND: Degenerative lumbar stenosis associated with spondylolisthesis is
      common in elderly patients. The most common symptoms are those of neurogenic
      claudication with leg pain. Surgery is indicated for those who fail conservative
      management. The generally accepted recommendation is to perform a laminectomy and
      a fusion at the involved level. METHODS: We reviewed our results for minimally
      invasive single-level decompression without fusion performed by the senior author
      in patients with symptomatic lumbar stenosis with spondylolisthesis with no
      dynamic instability from 2008 to 2011 at a single institution. Outcomes were
      measured using the visual analog scale (VAS), Prolo Economic Functional Rating
      Scale, and revised Oswestry Disability Index (ODI) at initial presentation and at
      3-month, 6-month, and 1-year follow-up time points. RESULTS: Records for 28
      patients (19 males, 9 females) were reviewed. The success rate, defined as
      improvement in pain and functional outcome without the need for surgical fusion,
      was 86%. VAS scores decreased by 6.3 points, Prolo scores increased by 3.5
      points, and the ODI decreased by 31% at 1 year. All changes were statistically
      significant. CONCLUSION: Minimally invasive decompression alone can be a
      reasonable alternative to decompression and fusion for patients with
      spondylolisthetic lumbar stenosis and neurogenic claudication with leg pain.
      Decompression without fusion should be considered for older patients and for
      patients who are not ideal fusion candidates.

PMID- 24688333
TI  - Midline minimally invasive placement of spinal cord stimulators: a technical
      note.
AB  - BACKGROUND: Spinal cord stimulators (SCSs) have conventionally been implanted
      through open approaches requiring extensive muscle dissection to perform
      laminectomies and permanently place the paddle lead. This approach could
      contribute to worsening the pain syndrome in patients who experience chronic
      pain. In an attempt to reduce operative times, minimize blood loss and
      postoperative pain, and ease the technical challenges of placing the paddle lead
      in the midline via a paramedian and off-midline incision, we designed a new
      minimally invasive surgery (MIS) technique to place the paddle lead using a
      tubular retractor system through a true midline approach. METHODS: We performed a
      retrospective review of all MIS paddle lead placements performed by the senior
      author between October 2010 and June 2013. Patient demographics; clinical
      indications for placement of paddle lead; location of paddle lead; and
      perioperative data including blood loss, length of surgery, and surgical and
      perioperative morbidity were recorded. RESULTS: Between October 2010 and June
      2013, 78 patients had MIS placement of paddle lead SCSs. Patient ages ranged from
      27 to 87 years old, with a mean age of 59. The most common levels for paddle lead
      placement were T8 and T9. No minor or major neurologic complications occurred in
      our patient population. No patient was readmitted after being discharged from the
      hospital and all surgeries were outpatient procedures. We had a migration rate
      comparable to open techniques and minimal blood loss. CONCLUSION: Our technique
      is safe and effective and carries minimal surgical morbidity compared to standard
      open techniques for placement of SCSs.

PMID- 24688332
TI  - The effects of lumbar facet dowels on joint stiffness: a biomechanical study.
AB  - BACKGROUND: Facet joint arthrosis may play a significant role in low back pain
      generation. The placement of facet dowels is a percutaneous treatment that aims
      to fuse the facets and increase joint stiffness. In this cadaveric study, we
      evaluated spine stiffness after facet dowel insertion in combination with several
      surgical procedures and determined which motions promote dowel migration.
      METHODS: Six fresh frozen lumbar spines were tested in flexion-extension, lateral
      bending, and axial rotation. Spine stiffness was determined for the intact
      specimens, after L4 laminectomy, and after bilateral L4-L5 facet dowel placement,
      respectively. One specimen underwent a unilateral transforaminal lumbar interbody
      fusion (TLIF) construct and another underwent extreme lateral interbody fusion
      (XLIF) graft (22 mm) placement, followed by placement of facet dowels.
      Afterwards, the specimens were subjected to 10,000 cycles of fatigue testing in
      flexion-extension or axial rotation. RESULTS: The overall decrease in stiffness
      after laminectomy was 4.6%. Facet dowel placement increased overall stiffness by
      7.2%. The greatest increase was seen with axial rotation (13%), compared to
      flexion, extension, and lateral bending (9.5%, 2.3%, and 5.6%, respectively). The
      TLIF and XLIF plus dowel construct increased specimen stiffness to 266% and 163%
      of baseline, respectively. After fatigue testing, dowel migration was detected by
      computed tomography in the 2 uninstrumented specimens undergoing axial rotation
      cycling. CONCLUSION: Facet dowels increase the stiffness of the motion segment to
      which they are applied and can be used in conjunction with laminectomy procedures
      to increase the stiffness of the joint. However, dowel migration can occur after
      axial rotation movements. Hybrid TLIF or XLIF plus facet dowel constructs have
      significantly higher stiffness than noninstrumented ones and may prevent dowel
      migration.

PMID- 24688334
TI  - Intraoperative neurophysiological monitoring for minimally invasive 1- and 2
      level transforaminal lumbar interbody fusion: does it improve patient outcome?
AB  - BACKGROUND: Despite the widespread use of intraoperative monitoring (IOM) in many
      types of spinal surgeries, an absence of data comparing monitored a nd
      unmonitored postoperative outcomes places IOM's efficacy into question. A lack of
      consensus among surgeons about when to use monitoring also raises concerns about
      its overuse in routine and low-risk procedures. METHODS: We performed a
      retrospective database review of 112 patients undergoing a 1- or 2-level
      minimally invasive surgery transforaminal lumbar interbody fusion (MIS-TLIF). Our
      analysis focused on patient demographics, use of IOM, length of surgery, hospital
      length of stay, the perioperative complication of pedicle screw malposition, and
      average hospital cost. RESULTS: For the 73 patients who underwent MIS-TLIF with
      intraoperative neuromonitoring, their hospital length of stay (P=0.8) and need
      for pedicle screw revisions (P=0.93) were not statistically significant compared
      to the 39 patients who underwent MIS-TLIF procedures without IOM. The incidence
      of reoperation was 5.48% and 5.13%, and average length of stay was 3.25 days and
      3.13 days, respectively. However, the cost of surgery and the length of surgery
      were significantly higher in the monitored group compared to the nonmonitored
      group (P=0.008 and P=0.009, respectively). CONCLUSION: IOM is widely used in
      spine surgery, but our retrospective review shows that its use does not
      necessarily decrease the incidence of malpositioning of pedicle screws. In fact,
      no statistical difference was detected in the incidence of screw malposition in
      the 2 groups of patients. On the other hand, IOM adds cost and increases the
      length of surgery. Because the use of IOM did not make a difference in the
      incidence of pedicle screw malpositioning and because of the comparative cost
      analysis for both groups of patients, we believe that the use of IOM for MIS-TLIF
      provides no added benefit.

PMID- 24688335
TI  - Interlaminar epidural steroid injection for degenerative lumbar spinal canal
      stenosis: does the intervertebral level of performance matter?
AB  - BACKGROUND: Interlaminar epidural steroid injections (ILESIs) are commonly
      employed in the management of patients with symptomatic degenerative lumbar
      spinal canal stenosis despite little experimental evidence to guide technique
      optimization. One untested performance parameter is the intervertebral level at
      which the ILESI should be performed for maximum patient relief. METHODS: This
      study randomized patients with symptomatic degenerative lumbar spinal canal
      stenosis to receive an ILESI at the level of maximal spinal canal stenosis or at
      a normal/less stenotic intervertebral site 2 intervertebral levels cephalad to
      the level of maximal stenosis. Pain with ambulation and Roland Morris Disability
      Questionnaire scores were collected prior to the procedure and at 1-, 4-, and 12
      week follow-ups. RESULTS: Fifty-seven patients were enrolled. Thirty patients
      (Group 1) received an ILESI at the level of maximal stenosis; 27 patients (Group
      2) received an ILESI at a less stenotic level. The mean baseline preprocedural
      maximal pain with ambulation and disability scores for the 2 groups were not
      significantly different (P=0.94 and P=0.13, respectively). Patients' pain with
      ambulation scores were significantly lower in Group 1 compared to Group 2 at 1
      and 4 weeks postinjection, but they were not significantly lower at 12 weeks (1
      week, P=0.045; 4 weeks, P=0.049; 12 weeks, P=0.08). The mean Roland Morris
      Disability Questionnaire scores at 1, 4, and 12 weeks postinjection were
      significantly lower in Group 1 as compared to Group 2 (P=0.001, P=0.009, P=0.003,
      respectively). CONCLUSION: Results suggest that patient symptom improvement is
      optimized when the ILESI is performed at the intervertebral level of maximal
      stenosis.

PMID- 24688336
TI  - Likelihood of reaching minimal clinically important difference in adult spinal
      deformity: a comparison of operative and nonoperative treatment.
AB  - BACKGROUND: Few studies have examined threshold improvements in health-related
      quality of life (HRQOL) by measuring minimal clinically important differences
      (MCIDs) in treatment of adult spinal deformity. We hypothesized that patients
      undergoing operative treatment would be more likely to achieve MCID threshold
      improvement compared with those receiving nonoperative care, although a subset of
      nonoperative patients may still reach threshold. METHODS: We analyzed a
      multicenter, prospective, consecutive case series of 464 patients: 225
      nonoperative and 239 operative. To be included in the study, patients had to have
      adult spinal deformity, be older than 18 years, and have both baseline and 1-year
      follow-up HRQOL measures (Oswestry Disability Index [ODI], Short Form-36 [SF-36]
      health survey, and Scoliosis Research Society-22 [SRS-22] questionnaire). We
      compared the percentages of patients achieving established MCID thresholds
      between operative and nonoperative groups using risk ratios (RR) with a 95%
      confidence interval (CI). RESULTS: Compared to nonoperative patients, surgical
      patients demonstrated significant mean improvement (P<0.01) and were more likely
      to achieve threshold MCID improvement across all HRQOL scores (ODI RR = 7.37 [CI
      4.45, 12.21], SF-36 physical component score RR = 2.96 [CI 2.11, 4.15], SRS
      Activity RR = 3.16 [CI 2.32, 4.31]). Furthermore, operative patients were more
      likely to reach threshold MCID improvement in 2 or more HRQOL measures
      simultaneously and were less likely to deteriorate. CONCLUSION: Patients in both
      the operative and nonoperative treatment groups demonstrated improvement in at
      least one HRQOL measure at 1 year. However, surgical treatment was more likely to
      result in threshold improvement and more likely to lead to simultaneous
      improvement across multiple measures of ODI, SF-36, and SRS-22. Although a subset
      of nonoperative patients achieved threshold improvement, nonoperative patients
      were significantly less likely to improve in multiple HRQOL measures and more
      likely to sustain MCID deterioration or no change.

PMID- 24688337
TI  - Adjacent segment disease perspective and review of the literature.
AB  - BACKGROUND: Adjacent segment disease has become a common topic in spine surgery
      circles because of the significant increase in fusion surgery in recent years and
      the development of motion preservation technologies that theoretically should
      lead to a decrease in this pathology. The purpose of this review is to organize
      the evidence available in the current literature on this subject. METHODS: FOR
      THIS LITERATURE REVIEW, A SEARCH WAS CONDUCTED IN PUBMED WITH THE FOLLOWING
      KEYWORDS: adjacent segment degeneration and disease. Selection, review, and
      analysis of the literature were completed according to level of evidence.
      RESULTS: The PubMed search identified 850 articles, from which 41 articles were
      selected and reviewed. The incidence of adjacent segment disease in the cervical
      spine is close to 3% without a significant statistical difference between
      surgical techniques (fusion vs arthroplasty). Authors report the incidence of
      adjacent segment disease in the lumbar spine to range from 2% to 14%. Damage to
      the posterior ligamentous complex and sagittal imbalances are important risk
      factors for both degeneration and disease. CONCLUSION: Insufficient evidence
      exists at this point to support the idea that total disc arthroplasty is superior
      to fusion procedures in minimizing the incidence of adjacent segment disease. The
      etiology is most likely multifactorial but it is becoming abundantly clear that
      adjacent segment disease is not caused by motion segment fusion alone. Fusion
      plus the presence of abnormal end-fusion alignment appears to be a major factor
      in creating end-fusion stresses that result in adjacent segment degeneration and
      subsequent disease. The data presented cast further doubt on previously
      established rationales for total disc arthroplasty, at least with regard to the
      effect of total disc arthroplasty on adjacent segment degeneration pathology.

PMID- 24688338
TI  - Coccydynia: an overview of the anatomy, etiology, and treatment of coccyx pain.
AB  - BACKGROUND: Despite its small size, the coccyx has several important functions.
      Along with being the insertion site for multiple muscles, ligaments, and tendons,
      it also serves as one leg of the tripod-along with the ischial tuberosities-that
      provides weight-bearing support to a person in the seated position. The incidence
      of coccydynia (pain in the region of the coccyx) has not been reported, but
      factors associated with increased risk of developing coccydynia include obesity
      and female gender. METHODS: This article provides an overview of the anatomy,
      physiology, and treatment of coccydynia. RESULTS: Conservative treatment is
      successful in 90% of cases, and many cases resolve without medical treatment.
      Treatments for refractory cases include pelvic floor rehabilitation, manual
      manipulation and massage, transcutaneous electrical nerve stimulation,
      psychotherapy, steroid injections, nerve block, spinal cord stimulation, and
      surgical procedures. CONCLUSION: A multidisciplinary approach employing physical
      therapy, ergonomic adaptations, medications, injections, and, possibly,
      psychotherapy leads to the greatest chance of success in patients with refractory
      coccyx pain. Although new surgical techniques are emerging, more research is
      needed before their efficacy can be established.

PMID- 24688339
TI  - Effective spine triage: patterns of pain.
AB  - BACKGROUND: The most common cause of recurring lost time from work, low back pain
      is a huge burden on society. Medical training dictates that we must establish a
      cause for pain before we can treat it and then base our treatment on a recognized
      and agreed-upon pathology. But in the overwhelming majority of low back pain
      cases, the issue is nothing more than a minor mechanical malfunction, the
      inevitable consequence of normal wear and tear. The severity of the pain does not
      reflect the benign nature of the underlying problem and its limited extent makes
      a definitive diagnosis impossible. One important component of the solution is
      improved spinal triage. Using patterns or syndromes in the initial assessment of
      low back pain is gaining renewed interest and clinical acceptance. METHODS:
      Identifying a patient's pain pattern is achieved primarily through an assessment
      of the patient's history. The patient interview begins with a series of questions
      to determine the specific syndrome. A subsequent physical examination supports or
      refutes the findings in history. Combining information from the history with the
      findings of the physical examination, the clinician has the ability to rule out a
      number of potentially grim diagnoses. RESULTS: More than 90% of back pain
      patients have benign mechanical problems and their pain can be classified into 4
      distinct patterns: 2 back-dominant patterns and 2 leg-dominant patterns.
      CONCLUSION: A clinical perspective capable of recognizing a defined syndrome at
      first contact will lead to a better outcome. Most patients with low back pain can
      be treated successfully with simple, pattern-specific, noninvasive primary
      management. Patients without a pattern and those who do not respond as
      anticipated require further investigation and specialized care.

PMID- 24688340
TI  - How to assess a new patient for a multidisciplinary chronic pain rehabilitation
      program: a review article.
AB  - BACKGROUND: Chronic pain is a debilitating condition that affects people all over
      the world. To effectively treat chronic pain patients, assignment to patient
      centered functional restoration and psychological pain rehabilitation programs at
      an early stage is essential. METHODS: This article describes the initial patient
      screening and evaluation process for an interdisciplinary chronic pain
      rehabilitation program and highlights the relevant points that should be covered
      in each section of the initial assessment. RESULTS: A thorough, detailed history
      that includes an evaluation of the patient's pain, functional limitations, prior
      medications, prior procedures/interventions, substance abuse, and psychiatric
      disorders, as well as the patient's social, legal, and developmental histories,
      are key to the proper screening and appropriate treatment of patients with
      chronic pain. CONCLUSION: Thorough initial evaluation of patients is essential
      for proper enrollment in a chronic pain rehabilitation program. Such programs
      allow early treatment and reduce unnecessary health costs. Future prospective
      studies are needed to identify additional screening methods and triage tools to
      allow early admission of appropriate patients to these rehabilitation programs.

PMID- 24688341
TI  - Exercise in the management of chronic back pain.
AB  - BACKGROUND: Chronic back pain is one of the most common and expensive medical
      conditions facing today's population. Its costs are estimated to be as much as
      $100 billion in the United States alone. Causation is poorly understood and
      healthcare providers share little common language concerning this pain. In
      addition, costly medical diagnostic tests are performed that do little to inform
      treatment. In the era of evidence-based medicine, back pain healthcare providers
      must find better ways to communicate with one another. METHODS: The key to better
      communication is measurement within the context of an evidence-based, protocol
      driven clinical rehabilitation model. Measurement is the key to better
      communication among providers treating spinal pain. Measurement means acquiring
      both patient-reported outcomes (PROs) and clinician-based outcomes (CBOs).
      RESULTS: Musculoskeletal strengthening of the lumbar and cervical extensors has
      been shown to significantly reduce pain and provide successful clinical results
      for patients suffering from chronic back and neck pain. Lumbar strengthening has
      been successful because it is a safe exercise, it is prescribed based on
      pretreatment evaluation, and it provides objective measurements. CONCLUSION:
      Without measurement, clinical results rely more on opinion than on objectively
      prescribed courses of treatment. Although indirect measures (PROs) are typically
      presented in clinical papers and clinical reviews, they are not often used in
      normal physical therapy practices. Adding direct patient-performance measures
      (CBOs) creates a much clearer clinical picture. The key to understanding the
      value of clinical practice and its predictable impact on patient treatment is
      objective measurement.

PMID- 24688342
TI  - Neurologically intact patient following bilateral facet dislocation: case report
      and review of literature.
AB  - BACKGROUND: Complete spinal cord lesions and quadriplegia occur in 50%-84% of
      patients with bilateral facet dislocation. We present a patient who suffered both
      bilateral facet dislocation and bilateral pedicle fractures while remaining
      neurologically intact. Based on this case and our literature review, we
      hypothesize that bilateral facet dislocations without neurological deficits are
      accompanied by significant associated fractures that facilitate the maintenance
      of cervical spine canal patency. CASE REPORT: After a fall down a flight of
      stairs, an 86-year-old woman presented to the hospital complaining of neck pain.
      She denied numbness and weakness of her extremities. On physical examination she
      was neurologically intact without focal sensory or motor deficits and with normal
      reflexes throughout. Computed tomography (CT) of her neck demonstrated bilateral
      C5-C6 facet dislocation with locking of the C6 superior articular process dorsal
      to the C5 inferior articular process, as well as corresponding bilateral C6
      pedicle fractures. Additional acute fractures were identified on the thoracic CT.
      Magnetic resonance imaging demonstrated no spinal cord compression, edema, or
      hemorrhage. The patient had a C6-C7 anterior cervical discectomy and allograft
      fusion and a C5-T1 anterior cervical plate with screw fixation. CONCLUSION:
      Because bilateral facet dislocations without neurological deficits are rare, the
      most appropriate surgical intervention is not evident. We believe the best choice
      as a first step is an anterior cervical discectomy and allograft fusion with
      plating.

PMID- 24688343
TI  - Fetal surgery: the ochsner experience with in utero spina bifida repair.
AB  - BACKGROUND: Myelomeningocele is the most common form of congenital central
      nervous system defect that is compatible with life. Most patients with
      myelomeningocele have significant functional impairment of ambulation and bowel
      and bladder function, require permanent cerebrospinal fluid diversion with
      shunting, and have significant morbidity and mortality from hindbrain herniation
      (Chiari II malformation). The advent of intrauterine surgery has provided new
      opportunities to better address this lifelong debilitating disease. CASE REPORT:
      The patient was a 19-year-old gravida 2 para 1 at 22-6/7 weeks whose fetus was
      diagnosed with an open neural tube defect and further demonstrated to have
      ventriculomegaly and hindbrain herniation. Amniocentesis confirmed normal
      karyotype and the presence of acetylcholinesterase. After an intrauterine
      procedure, the patient underwent cesarean section at 35-5/7 weeks and delivered a
      male infant. His spinal incision was well healed at birth without any evidence of
      cerebrospinal fluid leakage, and his extremities were normal in appearance, range
      of motion, and movement. The infant also has maintained relatively normal, age
      appropriate bowel and bladder function and has no obvious neurologic deficit.
      CONCLUSION: As the benefit of fetal surgery becomes more widely accepted, quality
      of care and patient safety must be at the forefront of any institution's effort
      to offer fetal surgery. Given the current prevalence of spina bifida and the
      amount of resources required to treat this disease effectively either in utero or
      postnatally, it is our opinion that the treatment of spina bifida should be
      regionalized to tertiary referral centers with the interdisciplinary expertise to
      offer comprehensive treatment for all aspects of the disease and all phases of
      care for the patients.

PMID- 24688344
TI  - Successful treatment of occipital neuralgia with implantable peripheral nerve
      stimulation in a pacemaker-dependent patient.
AB  - BACKGROUND: Peripheral nerve stimulation has been used to treat patients with
      occipital nerve-related chronic headaches who have been unsuccessful with less
      invasive therapeutic approaches. Patients with pacemaker-dependent cardiac
      conduction abnormalities require unique consideration prior to the implantation
      of peripheral nerve stimulators because the placement of the devices may lead to
      failure of the systems secondary to electromagnetic interference or crosstalk
      between the devices. CASE REPORT: An 86-year-old female who suffered from chronic
      right-sided cervicogenic headaches and neck pain had received only temporary
      relief from previous treatments. Additional comorbidities included longstanding
      pacemaker-dependent atrioventricular node conduction disease. Because the extent
      to which nerve stimulators electrically interact with pacemakers is unclear, we
      tunneled the leads to the lumbar region of the back and placed the generator on
      the contralateral side to the pacemaker to minimize the chance that the 2 devices
      would interfere. The patient has remained pain free for 1 year since
      implantation. CONCLUSION: Although no current published trials evaluate the
      degree of interference between medical devices, case reports increasingly suggest
      that simultaneous implantation of a spinal cord stimulator and pacemaker is safe
      as long as precautions are taken and the devices are checked periodically,
      particularly when the devices are adjusted.

PMID- 24688345
TI  - Caudal vertebral body fractures following lateral interbody fusion in
      nonosteoporotic patients.
AB  - BACKGROUND: The minimally invasive lateral transpsoas approach for lumbar fusions
      has become increasingly popular. However, vertebral body fractures have been
      reported after this procedure, particularly in patients with osteoporosis and
      patients undergoing multilevel fusions. We evaluated the risk factors for caudal
      vertebral body fractures in 2 nonosteoporotic patients with single-level disease.
      CASE REPORTS: Two patients presented with several years' history of
      incapacitating chronic low back pain and intermittent radicular pain. Diagnostic
      imaging in both cases demonstrated grade 1 degenerative spondylolisthesis. The
      patients underwent a lateral transpsoas interbody fusion, with lateral plate
      fixation in 1 patient and standalone lateral fusion in the other. The operations
      were performed without any incidents and both patients experienced immediate
      symptom relief. Both patients returned several weeks later with excruciating low
      back pain, without any postoperative history of trauma or heavy lifting.
      Diagnostic imaging in both patients showed a coronal fracture of the inferior
      vertebral body. The patients underwent urgent revision surgery involving
      posterior supplementation with pedicle screw and rod constructs and
      posterolateral fusion. CONCLUSION: Caudal vertebral body fracture in patients
      with normal bone quality is a major potential complication after the minimally
      invasive lateral approach for lumbar fusions. Risk factors may include placement
      of a lateral plate, the size of the smaller anteroposterior cage, endplate
      violation, and oblique placement of the interbody cage.

PMID- 24688346
TI  - Urgent cesarean section in a patient with a spinal cord stimulator: implications
      for surgery and anesthesia.
AB  - BACKGROUND: Spinal cord stimulation used in the treatment of chronic pain is
      offered to women of child-bearing age. This practice warrants special
      consideration on the part of the obstetricians and anesthesiologists charged with
      their care. CASE REPORT: We report the instance of a parturient with a spinal
      cord stimulator who presented for urgent cesarean section. In spite of the
      patient's daunting back examination, the suitability of neuraxial anesthesia for
      cesarean delivery was rapidly determined by accessing images in our centerwide
      electronic medical record system. CONCLUSION: Accepted approaches to managing
      labor and delivery-such as neuraxial anesthesia and analgesia-need not be denied
      patients with spinal cord stimulators. Whenever possible, however, the pain
      specialist should communicate the specific characteristics of the implanted
      device to the team who will manage the patient in the peripartal period.

PMID- 24688348
TI  - 14(th) Annual Southern Hospital Medicine Conference Abstracts.

PMID- 24688347
TI  - One-stage resection of giant invasive thoracic schwannoma: case report and review
      of literature.
AB  - BACKGROUND: Schwannomas comprise approximately 25% of all spinal tumors, being
      the third most frequent soft-tissue tumor after hemangiomas and lipomas. Grade 5
      invasive giant schwannomas erode the vertebral bodies, involve 2 or more levels,
      and invade the myofascial planes. Because 3 compartments are involved, these
      tumors represent a surgical challenge and frequently require staged surgeries
      with a multidisciplinary surgical team. CASE REPORT: We report the case of a 62
      year-old female who presented with intermittent upper back pain for 3 years. A
      magnetic resonance imaging scan of the thoracic spine showed a mass invading the
      vertebral body, pedicle, and lamina of T4 and part of T3 and T5. Needle biopsy
      confirmed the diagnosis of schwannoma. The patient underwent surgery using a
      parascapular extracavitary costotransversectomy approach. CONCLUSION: Giant
      invasive spinal schwannomas are rare in the thoracic spine, and surgical
      approaches usually have entailed multiple-stage surgeries with the assistance of
      other surgical specialties. Our 1-stage complete surgical resection of a giant
      invasive spinal schwannoma used a parascapular costotransversectomy approach that
      maintained spinal stability and thus avoided the need for instrumentation.

PMID- 24688349
TI  - Reliability and Validity of PROMIS Cognitive Abilities and Cognitive Concerns
      Scales Among People with Multiple Sclerosis.
AB  - BACKGROUND: Cognitive impairment is among the most debilitating outcomes of
      multiple sclerosis (MS). Although several neuropsychological tests and self
      report cognitive measures have been used to assess cognitive impairment, they may
      not be sensitive to change over time, or may not be feasible to administer in a
      clinical setting. The purpose of this study was to assess the reliability and
      validity of the 8-item PROMIS Cognitive Abilities and Cognitive Concerns Scales
      in a large community-based sample of people with MS. The PROMIS Cognitive
      Abilities and Cognitive Concerns Scales derive from the National Institutes of
      Health-funded Patient Reported Outcomes Measurement Information System (PROMIS),
      an item repository that capitalizes on recent psychometric advances to produce
      short, psychometrically sound health measures. METHODS: Mailed survey data were
      collected from 322 individuals recruited from two National Multiple Sclerosis
      Society chapters in a southwestern state. RESULTS: Both cognitive scales
      demonstrated high internal consistency reliability and were moderately correlated
      with self-reported depressive symptoms, self-efficacy, barriers to health
      promotion, health, and functional status (all correlation coefficients >0.35). In
      hierarchical regression analysis, the PROMIS Cognitive Concerns score added
      significant unique variance to the prediction of MS Incapacity Status after
      controlling for self-reported depressive symptoms, exercise, spiritual growth,
      and global health. Those who were unemployed owing to their disabilities had
      significantly lower PROMIS Cognitive Abilities scores and higher Cognitive
      Concerns scores than those who were working or those who were retired or not
      working for other reasons. CONCLUSIONS: The PROMIS Cognitive Abilities and
      Cognitive Concerns Scales are short, psychometrically sound measures that assess
      an important dimension of functioning and health for people with MS.

PMID- 24688350
TI  - Factors associated with health-related quality of life among older people with
      multiple sclerosis.
AB  - BACKGROUND: This study was conducted to determine which factors (clinical and
      demographic) are associated with mental and physical health-related quality of
      life (HRQOL) among people with multiple sclerosis (MS) aged 60 years and older.
      METHODS: Data were collected at four MS centers on Long Island, New York, from a
      total of 211 patients. Three surveys were administered that collected demographic
      information and included validated questionnaires measuring quality of life
      (QOL), cognition, depression, and disability. Multivariate linear regression
      analyses examined the relationship between patient demographics and scores on
      standardized scales measuring mental and physical HRQOL (Multiple Sclerosis
      Quality of Life-54). Variables included in the regression models were selected on
      the basis of the Andersen Healthcare Utilization model. This framework
      encompasses the multiple influences on health status, including predisposing
      characteristics, enabling resources, need, and health behavior. RESULTS: We found
      that mental HRQOL was negatively associated with having a high school education
      or less, risk of neurologic impairment, physical disability, and depression. No
      variables were positively associated with mental HRQOL. Physical HRQOL was
      negatively associated with risk of neurologic impairment, physical disability,
      depression, and the comorbidity of thyroid disease. However, patient employment
      and, surprisingly, being widowed were positively associated with physical HRQOL.
      These findings are consistent with those of similar studies among younger
      patients in which lower HRQOL was associated with increased disability,
      depression, risk of neurologic impairment, and lower levels of education.
      CONCLUSIONS: The findings that patient employment and being widowed were
      associated with better physical HRQOL suggest that older patients have the
      ability to adapt and adjust to the challenges of MS over time. Clinicians should
      regularly screen for HRQOL in older patients with MS.

PMID- 24688351
TI  - Pelvic floor disorders and multiple sclerosis: are patients satisfied with their
      care?
AB  - BACKGROUND: Despite recent efforts to educate multiple sclerosis (MS) health-care
      providers about the importance of pelvic floor disorders (urinary, bowel, and
      sexual dysfunction), no data are currently available to assess outcomes of these
      efforts in terms of patient satisfaction. METHODS: As part of the fall 2010 North
      American Research Committee on Multiple Sclerosis survey, we conducted a
      prospective, survey-based cohort study (N = 14,268) to evaluate patient
      satisfaction with the current evaluation and treatment of pelvic floor disorders.
      Patients were queried about 1) bother from bladder, bowel, or sexual symptoms; 2)
      whether they had been evaluated by a health-care provider for pelvic floor issues
      in the last 12 months; and 3) satisfaction with the evaluation and treatment they
      received, on a 5-point Likert scale. Patients were also asked whether these
      treatments had affected their quality of life (7-point Likert scale). RESULTS: A
      total of 9397 responses were received (response rate of 65.9%); respondents were
      primarily white (89%) and female (77.4%). Moderate-to-severe pelvic floor
      symptoms were reported by one-third of patients (bladder, 41%; bowel, 30%;
      sexual, 42%). Most respondents had been asked about bladder (61%) or bowel (50%)
      issues by their health-care providers, but only 20% had been queried about sexual
      dysfunction. Most respondents were moderately to very satisfied with the
      management of their bladder and bowel disorders but significantly less satisfied
      with that of sexual dysfunction. CONCLUSIONS: While MS patients are generally
      satisfied with current management of bladder and bowel dysfunction, improvement
      is needed in that of sexual dysfunction.

PMID- 24688352
TI  - Interest in providing multiple sclerosis care and subspecializing in multiple
      sclerosis among neurology residents.
AB  - BACKGROUND: Although detailed knowledge regarding treatment options for multiple
      sclerosis (MS) patients is largely limited to neurologists, shortages in the
      neurologist workforce, including MS subspecialists, are predicted. Thus, MS
      patients may have difficulties in gaining access to appropriate care. No
      systematic evaluation has yet been performed of the number of neurology residents
      planning to pursue MS subspecialization. This study identifies factors affecting
      interest in providing MS patient care or MS subspecialization among current
      neurology residents. METHODS: We randomly selected half of all Accreditation
      Council of Graduate Medical Education-certified neurology residency programs in
      the continental United States to receive the neurology resident survey. Completed
      surveys were received from 218 residents. RESULTS: Residents were significantly
      more likely to have increased interest in MS care when they participated in MS
      research, were interested in teaching, and indicated that the "ability to improve
      patient outcomes and quality of life" was a positive factor influencing their
      desire to provide MS patient care. Residents who were interested in providing MS
      care, interested in teaching, and indicated that "research opportunities" was a
      positive factor for providing MS patient care were significantly more likely to
      express interest in MS subspecialization. CONCLUSIONS: Increasing opportunities
      to interact with MS patients, learn about MS care, and participate in MS research
      may increase interest in MS care and subspecialization among neurology residents.
      Opportunities to educate residents regarding MS patient care may affect
      residents' attitudes.

PMID- 24688353
TI  - The TRUST (EvaluaTion of Bladder Function in Relapsing-Remitting MUltiple
      Sclerosis Patients Treated with Natalizumab) Observational Study.
AB  - BACKGROUND: Bladder dysfunction is a common symptom of multiple sclerosis (MS).
      This study was designed to evaluate effects of natalizumab on bladder function in
      patients with relapsing-remitting MS. METHODS: The TRUST (EvaluaTion of Bladder
      Function in Relapsing-Remitting MUltiple Sclerosis Patients Treated with
      Natalizumab) study was an open-label, single-arm, two-center study. Natalizumab
      naive MS patients with disabling bladder dysfunction and initiating natalizumab
      were enrolled and followed for 6 months. The primary endpoint was change in the
      Urogenital Distress Inventory short form (UDI-6) score from baseline. Change in
      Incontinence Impact Questionnaire short form (IIQ-7) score from baseline was a
      secondary endpoint. RESULTS: Thirty patients were enrolled. Mean baseline
      characteristics were age 49.9 years, Expanded Disability Status Scale score 4.6,
      number of relapses in previous year 2.4, UDI-6 score 10.4, and IIQ-7 score 12.3.
      Mean changes in UDI-6 and IIQ-7 scores were significantly improved from baseline
      beginning at week 4 and up to week 24; mean improvements at 24 weeks were 4.4 (P
      < .0001) and 4.9 (P = .0005) points, respectively. At week 24, 85.7% and 78.6% of
      patients demonstrated improvements from baseline in UDI-6 and IIQ-7 scores,
      respectively. CONCLUSIONS: Incontinence-related quality of life as measured by
      UDI-6 and IIQ-7 scores improved significantly during natalizumab treatment.

PMID- 24688354
TI  - Comparing two conditions of administering the six-minute walk test in people with
      multiple sclerosis.
AB  - OBJECTIVE: This quasi-experimental study was conducted to determine whether
      differences existed in the total distance walked and energy expended between two
      conditions of administering the 6-Minute Walk test (6MW) across different levels
      of disability in people with multiple sclerosis (MS). METHODS: The sample
      comprised 160 individuals with MS. One group of participants (n = 82) completed a
      6MW while wearing a portable metabolic unit (K4b(2), Cosmed, Italy) in a square
      hallway with four corridors and performing 90 degrees  turns. Another group (n =
      78) completed a 6MW while wearing the same metabolic unit in a single corridor
      and performing 180 degrees  turns. Main outcome measures included total distance
      walked (in feet) and oxygen consumption (in milliliters per minute) expressed as
      30-second averages for 1 minute before the 6MW and over the entire 6MW.
      Disability status was assessed using the Patient-Determined Disease Steps scale.
      RESULTS: Participants undertaking the 6MW in a single corridor (1412 ft) walked
      37 ft (2.7%) farther than those undertaking the test in a square hallway (1375
      ft), but this difference was not statistically significant (F = 0.45, P = .51).
      Those completing the 6MW in a single corridor expended more energy than those
      completing the 6MW in the square hallway with four corridors (F = 3.41, P < .01).
      CONCLUSIONS: Either protocol is acceptable, but researchers should be aware of
      the additional physiological demands when administering the 6MW in a single
      corridor with 180 degrees  turns.

PMID- 24688356
TI  - Editorial.

PMID- 24688355
TI  - Nurses' perspective on approaches to limit flu-like symptoms during interferon
      therapy for multiple sclerosis.
AB  - BACKGROUND: Several interferon beta (IFNbeta) formulations are approved for first
      line use as disease-modifying therapies to treat patients with multiple sclerosis
      (MS). Systemic post-injection reactions, often termed flu-like symptoms (FLS),
      occur in approximately half of all patients treated with IFNbetas and can affect
      adherence to therapy. These symptoms, which include pyrexia, chills, malaise,
      myalgia, and headaches, usually resolve within 24 hours or persist intermittently
      following each injection. Because FLS, which usually occur early in the treatment
      course and diminish over time, are a primary cause of nonadherence to IFNbeta
      therapy, it is important to employ strategies that can attenuate these side
      effects. METHODS: To identify interventions effective in limiting FLS, a panel of
      United States-based nurses with expertise in MS patient care was convened and a
      literature review completed. RESULTS: Panel consensus was reached on specific
      interventions that can attenuate FLS. These prevention and mitigation strategies
      include dose titration, analgesia, and optimal injection timing, as well as other
      techniques that panel members have found useful in their clinical practice
      experience. CONCLUSIONS: These measures, in addition to effective patient
      education, will help to reduce the incidence of FLS secondary to IFNbeta therapy,
      improve patient medication adherence, and positively affect long-term clinical
      outcomes.

PMID- 24688357
TI  - Application of butterfly Clos-network in network-on-chip.
AB  - This paper studied the topology of NoC (Network-on-Chip). By combining the
      characteristics of the Clos network and butterfly network, a new topology named
      BFC (Butterfly Clos-network) network was proposed. This topology integrates
      several modules, which belongs to the same layer but different dimensions, into a
      new module. In the BFC network, a bidirectional link is used to complete
      information exchange, instead of information exchange between different layers in
      the original network. During the routing period, other nondestination nodes can
      be used as middle stages to transfer data packets to complete the routing
      mission. Therefore, this topology has the characteristic of multistage.
      Simulation analyses show that BFC inherits the rich path diversity of Clos
      network, and it has a better performance than butterfly network in throughput and
      delay in a quite congested traffic pattern. 

PMID- 24688358
TI  - A comparative study on improved Arrhenius-type and artificial neural network
      models to predict high-temperature flow behaviors in 20MnNiMo alloy.
AB  - The stress-strain data of 20MnNiMo alloy were collected from a series of hot
      compressions on Gleeble-1500 thermal-mechanical simulator in the temperature
      range of 1173 ~ 1473 K and strain rate range of 0.01 ~ 10 s(-1). Based on the
      experimental data, the improved Arrhenius-type constitutive model and the
      artificial neural network (ANN) model were established to predict the high
      temperature flow stress of as-cast 20MnNiMo alloy. The accuracy and reliability
      of the improved Arrhenius-type model and the trained ANN model were further
      evaluated in terms of the correlation coefficient (R), the average absolute
      relative error (AARE), and the relative error (eta). For the former, R and AARE
      were found to be 0.9954 and 5.26%, respectively, while, for the latter, 0.9997
      and 1.02%, respectively. The relative errors (eta) of the improved Arrhenius-type
      model and the ANN model were, respectively, in the range of -39.99% ~ 35.05% and 
      3.77% ~ 16.74%. As for the former, only 16.3% of the test data set possesses eta
      values within +/- 1%, while, as for the latter, more than 79% possesses. The
      results indicate that the ANN model presents a higher predictable ability than
      the improved Arrhenius-type constitutive model.

PMID- 24688360
TI  - High-accuracy approximation of high-rank derivatives: isotropic finite
      differences based on lattice-Boltzmann stencils.
AB  - We propose isotropic finite differences for high-accuracy approximation of high
      rank derivatives. These finite differences are based on direct application of
      lattice-Boltzmann stencils. The presented finite-difference expressions are valid
      in any dimension, particularly in two and three dimensions, and any lattice
      Boltzmann stencil isotropic enough can be utilized. A theoretical basis for the
      proposed utilization of lattice-Boltzmann stencils in the approximation of high
      rank derivatives is established. In particular, the isotropy and accuracy
      properties of the proposed approximations are derived directly from this basis.
      Furthermore, in this formal development, we extend the theory of Hermite
      polynomial tensors in the case of discrete spaces and present expressions for the
      discrete inner products between monomials and Hermite polynomial tensors. In
      addition, we prove an equivalency between two approaches for constructing lattice
      Boltzmann stencils. For the numerical verification of the presented finite
      differences, we introduce 5th-, 6th-, and 8th-order two-dimensional lattice
      Boltzmann stencils. 

PMID- 24688359
TI  - Prediction of early response to chemotherapy in lung cancer by using diffusion
      weighted MR imaging.
AB  - PURPOSE: To determine whether change of apparent diffusion coefficient (ADC)
      value could predict early response to chemotherapy in lung cancer. MATERIALS AND
      METHODS: Twenty-five patients with advanced non-small cell lung cancer underwent
      chest MR imaging including DWI before and at the end of the first cycle of
      chemotherapy. The tumor's mean ADC value and diameters on MR images were
      calculated and compared. The grouping reference was based on serial CT scans
      according to Response Evaluation Criteria in Solid Tumors. Logistic regression
      was applied to assess treatment response prediction ability of ADC value and
      diameters. RESULTS: The change of ADC value in partial response group was higher
      than that in stable disease group (P = 0.004). ROC curve showed that ADC value
      could predict treatment response with 100% sensitivity, 64.71% specificity,
      57.14% positive predictive value, 100% negative predictive value, and 82.7%
      accuracy. The area under the curve for combination of ADC value and longest
      diameter change was higher than any parameter alone (P <= 0.01). CONCLUSIONS: The
      change of ADC value may be a sensitive indicator to predict early response to
      chemotherapy in lung cancer. Prediction ability could be improved by combining
      the change of ADC value and longest diameter.

PMID- 24688361
TI  - Experimental investigation for fault diagnosis based on a hybrid approach using
      wavelet packet and support vector classification.
AB  - To deal with the difficulty to obtain a large number of fault samples under the
      practical condition for mechanical fault diagnosis, a hybrid method that combined
      wavelet packet decomposition and support vector classification (SVC) is proposed.
      The wavelet packet is employed to decompose the vibration signal to obtain the
      energy ratio in each frequency band. Taking energy ratios as feature vectors, the
      pattern recognition results are obtained by the SVC. The rolling bearing and gear
      fault diagnostic results of the typical experimental platform show that the
      present approach is robust to noise and has higher classification accuracy and,
      thus, provides a better way to diagnose mechanical faults under the condition of
      small fault samples. 

PMID- 24688362
TI  - Comparison of geostatistical kriging algorithms for intertidal surface sediment
      facies mapping with grain size data.
AB  - This paper compares the predictive performance of different geostatistical
      kriging algorithms for intertidal surface sediment facies mapping using grain
      size data. Indicator kriging, which maps facies types from conditional
      probabilities of predefined facies types, is first considered. In the second
      approach, grain size fractions are first predicted using cokriging and the facies
      types are then mapped. As grain size fractions are compositional data, their
      characteristics should be considered during spatial prediction. For efficient
      prediction of compositional data, additive log-ratio transformation is applied
      before cokriging analysis. The predictive performance of cokriging of the
      transformed variables is compared with that of cokriging of raw fractions in
      terms of both prediction errors of fractions and facies mapping accuracy. From a
      case study of the Baramarae tidal flat, Korea, the mapping method based on
      cokriging of log-ratio transformation of fractions outperformed the one based on
      cokriging of untransformed fractions in the prediction of fractions and produced
      the best facies mapping accuracy. Indicator kriging that could not account for
      the variation of fractions within each facies type showed the worst mapping
      accuracy. These case study results indicate that the proper processing of grain
      size fractions as compositional data is important for reliable facies mapping. 

PMID- 24688363
TI  - Potential regulatory role of gibberellic and humic acids in sprouting of
      Chlorophytum borivilianum tubers.
AB  - Tubers of safed musli (Chlorophytum borivilianum) were immersed in three
      different concentrations of gibberellic acid (GA3) or humic acid (HA) prior to
      planting. The highest concentration of GA3 (20 mg L(-1)) and all concentrations
      of HA (5, 10, and 15%) appeared to hasten tuber sprouting and promote uniform
      sprouting pattern. The use of 20 mg L(-1) GA3 or 15% HA successfully improved
      sprouting and mean sprouting time. Safed musli growth and development was
      improved through the increase in the number of leaves, total leaf area, leaf area
      index, and total fibrous root length. This directly influenced the number of new
      tubers formed. The use of 20 mg L(-1) GA3 or 15% HA gave similar response with
      nonsignificant difference among them. However, due to the cost of production, the
      result from this study suggests that 15% HA should be used to obtain improved
      sprouting percentage, homogeneous stand establishment, efficient plant growth and
      development, and increased yield of safed musli.

PMID- 24688364
TI  - Detection of lungs status using morphological complexities of respiratory sounds.
AB  - Traditionally, the clinical diagnosis of a respiratory disease is made from a
      careful clinical examination including chest auscultation. Objective analysis and
      automatic interpretation of the lung sound based on its physical characters are
      strongly warranted to assist clinical practice. In this paper, a new method is
      proposed to distinguish between the normal and the abnormal subjects using the
      morphological complexities of the lung sound signals. The morphological embedded
      complexities used in these experiments have been calculated in terms of texture
      information (lacunarity), irregularity index (sample entropy), third order moment
      (skewness), and fourth order moment (Kurtosis). These features are extracted from
      a mixed data set of 10 normal and 20 abnormal subjects and are analyzed using two
      different classifiers: extreme learning machine (ELM) and support vector machine
      (SVM) network. The results are obtained using 5-fold cross-validation. The
      performance of the proposed method is compared with a wavelet analysis based
      method. The developed algorithm gives a better accuracy of 92.86% and sensitivity
      of 86.30% and specificity of 86.90% for a composite feature vector of four
      morphological indices. 

PMID- 24688366
TI  - Heat and mass transfer with condensation in capillary porous bodies.
AB  - The purpose of this present work is related to wetting process analysis caused by
      condensation phenomena in capillary porous material by using a numerical
      simulation. Special emphasis is given to the study of the mechanism involved and
      the evaluation of classical theoretical models used as a predictive tool. A
      further discussion will be given for the distribution of the liquid phase for
      both its pendular and its funicular state and its consequence on diffusion
      coefficients of the mathematical model used. Beyond the complexity of the
      interaction effects between vaporisation-condensation processes on the gas-liquid
      interfaces, the comparison between experimental and numerical simulations permits
      to identify the specific contribution and the relative part of mass and energy
      transport parameters. This analysis allows us to understand the contribution of
      each part of the mathematical model used and to simplify the study. 

PMID- 24688365
TI  - Pharmacodynamics of TRPV1 agonists in a bioassay using human PC-3 cells.
AB  - PURPOSE: TRPV1 is a multimodal channel mainly expressed in sensory neurons. We
      aimed to explore the pharmacodynamics of the TRPV1 agonists, capsaicin, natural
      capsaicinoids, and piperine in an in vitro bioassay using human PC-3 cells and to
      examine desensitization and the effect of the specific antagonist SB366791.
      METHODS: PC-3 cells expressing TRPV1 were incubated with Fluo-4. Fluorescence
      emission changes following exposition to agonists with and without preincubation
      with antagonists were assessed and referred to maximal fluorescence following the
      addition of ionomycin. Concentration-response curves were fitted to the Hill
      equation. RESULTS: Capsaicin and piperine had similar pharmacodynamics (E max
      204.8 +/- 184.3% piperine versus 176.6 +/- 35.83% capsaicin, P = 0.8814, Hill
      coefficient 0.70 +/- 0.50 piperine versus 1.59 +/- 0.86 capsaicin, P = 0.3752).
      In contrast, capsaicinoids had lower E max (40.99 +/- 6.14% capsaicinoids versus
      176.6 +/- 35.83% capsaicin, P < 0.001). All the TRPV1 agonists showed significant
      desensitization after the second exposition and their effects were strongly
      inhibited by SB366791. CONCLUSION: TRPV1 receptor is successfully stimulated by
      capsaicin, piperine, and natural capsaicinoids. These agonists present
      desensitization and their effect is significantly reduced by a TRPV1-specific
      antagonist. In addition, PC-3 cell bioassays proved useful in the study of TRPV1
      pharmacodynamics.

PMID- 24688367
TI  - Modeling relief demands in an emergency supply chain system under large-scale
      disasters based on a queuing network.
AB  - This paper presents a multiple-rescue model for an emergency supply chain system
      under uncertainties in large-scale affected area of disasters. The proposed
      methodology takes into consideration that the rescue demands caused by a large
      scale disaster are scattered in several locations; the servers are arranged in
      multiple echelons (resource depots, distribution centers, and rescue center
      sites) located in different places but are coordinated within one emergency
      supply chain system; depending on the types of rescue demands, one or more
      distinct servers dispatch emergency resources in different vehicle routes, and
      emergency rescue services queue in multiple rescue-demand locations. This
      emergency system is modeled as a minimal queuing response time model of location
      and allocation. A solution to this complex mathematical problem is developed
      based on genetic algorithm. Finally, a case study of an emergency supply chain
      system operating in Shanghai is discussed. The results demonstrate the robustness
      and applicability of the proposed model. 

PMID- 24688369
TI  - A review on using crumb rubber in reinforcement of asphalt pavement.
AB  - An immense problem affecting environmental pollution is the increase of waste
      tyre vehicles. In an attempt to decrease the magnitude of this issue, crumb
      rubber modifier (CRM) obtained from waste tyre rubber has gained interest in
      asphalt reinforcement. The use of crumb rubber in the reinforcement of asphalt is
      considered as a smart solution for sustainable development by reusing waste
      materials, and it is believed that crumb rubber modifier (CRM) could be an
      alternative polymer material in improving hot mix asphalt performance properties.
      In this paper, a critical review on the use of crumb rubber in reinforcement of
      asphalt pavement will be presented and discussed. It will also include a review
      on the effects of CRM on the stiffness, rutting, and fatigue resistance of road
      pavement construction. 

PMID- 24688368
TI  - Fiber optic projection-imaging system for shape measurement in confined space.
AB  - A fiber-based projection-imaging system is proposed for shape measurement in
      confined space. Owing to the flexibility of imaging fibers, the system can be
      used in special scenarios that are difficult for conventional experimental
      setups. Three experiments: open space, closed space, and underwater are designed
      to demonstrate the strength and weakness of the system. It is shown that when
      proper alignment is possible, relatively high accuracy can be achieved; the error
      is less than 2% of the overall height of a specimen. In situations where
      alignment is difficult, significantly increased error is observed. The error is
      in the form of gross-scale geometrical distortion; for example, flat surface is
      reconstructed with curvature. In addition, the imaging fibers may introduce fine
      scale noise into phase measurement, which has to be suppressed by smoothing
      filters. Based on results and analysis, it is found that although a fiber-based
      system has its unique strength, existing calibration and processing methods for
      fringe patterns have to be modified to overcome its drawbacks so as to
      accommodate wider applications. 

PMID- 24688370
TI  - An adaptive hybrid algorithm based on particle swarm optimization and
      differential evolution for global optimization.
AB  - Particle swarm optimization (PSO) and differential evolution (DE) are both
      efficient and powerful population-based stochastic search techniques for solving
      optimization problems, which have been widely applied in many scientific and
      engineering fields. Unfortunately, both of them can easily fly into local optima
      and lack the ability of jumping out of local optima. A novel adaptive hybrid
      algorithm based on PSO and DE (HPSO-DE) is formulated by developing a balanced
      parameter between PSO and DE. Adaptive mutation is carried out on current
      population when the population clusters around local optima. The HPSO-DE enjoys
      the advantages of PSO and DE and maintains diversity of the population. Compared
      with PSO, DE, and their variants, the performance of HPSO-DE is competitive. The
      balanced parameter sensitivity is discussed in detail. 

PMID- 24688371
TI  - Pharmacological correction of stress-induced gastric ulceration by novel small
      molecule agents with antioxidant profile.
AB  - This study was designed to determine novel small-molecule agents influencing the
      pathogenesis of gastric lesions induced by stress. To achieve this goal, four
      novel organic compounds containing structural fragments with known antioxidant
      activity were synthesized, characterized by physicochemical methods, and
      evaluated in vivo at water immersion restraint conditions. The levels of lipid
      peroxidation products and activities of antioxidative system enzymes were
      measured in gastric mucosa and correlated with the observed gastroprotective
      activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with
      (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently
      decreases up to 86% stress-induced stomach ulceration in rats. Discovered small
      molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide
      dismutase, catalase, and xanthine oxidase in concerted directions.
      Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine
      and L-proline at least partially depends on the correction of gastric mucosa
      oxidative balance.

PMID- 24688372
TI  - Production of biodiesel from lipid of phytoplankton Chaetoceros calcitrans
      through ultrasonic method.
AB  - A research on production of biodiesel from lipid of phytoplankton Chaetoceros
      calcitrans through ultrasonic method has been done. In this research, we carried
      out a series of phytoplankton cultures to determine the optimum time of growth
      and biodiesel synthesis process from phytoplankton lipids. Process of biodiesel
      synthesis consists of two steps, that is, isolation of phytoplankton lipids and
      biodiesel synthesis from those lipids. Oil isolation process was carried out by
      ultrasonic extraction method using ethanol 96%, while biodiesel synthesis was
      carried out by transesterification reaction using methanol and KOH catalyst under
      sonication. Weight of biodiesel yield per biomass Chaetoceros calcitrans is
      35.35%. Characterization of biodiesel was well carried out in terms of physical
      properties which are density and viscosity and chemical properties which are FFA
      content, saponification value, and iodine value. These values meet the American
      Society for Testing and Materials (ASTM D6751) standard levels, except for the
      viscosity value which was 1.14 g . cm(-3).

PMID- 24688373
TI  - A mild synthesis of new aryl vinyl ethers and diethyl 1
      [(alkyl)(cyano)methyl]vinylphosphonates via the substitution of a 2,3
      difunctional allyl bromide.
AB  - A novel class of aryl vinyl ethers 3 and diethyl 3-cyano-3-alkylprop-1-en-2
      ylphosphonates 4 has been prepared, respectively, from coupling reaction of
      diethyl 1-(bromomethyl)-2-cyanovinylphosphonate 2 with phenols and Gilman
      reagents. 

PMID- 24688374
TI  - Comparison of solubilization capacity of resveratrol in sodium 3alpha, 12alpha 
      dihydroxy-7-oxo-5 beta-cholanoate and sodium dodecyl sulfate.
AB  - In this study we investigated resveratrol (trans-3,5,4'-trihydroxystilbene)
      solubilization with sodium 3alpha,12 alpha-dihydroxy-7-oxo-5 beta-cholanoate (S7
      OD) and sodium dodecyl sulfate (SDS). The investigation was aimed at determining
      whether large spherical micelles (SDS) or small longitudinal micelles (S7-OD) are
      more convenient for incorporation of resveratrol. Also, we studied resveratrol
      behavior in mixed micelles with mentioned surfactants using spectroflourimetric
      method as well as the effects of sodium chloride and urea on resveratrol
      solubilization capacity in the applied surfactants. Resveratrol solubilization
      curve was different in the investigated surfactants. Resveratrol solubilization
      curve for sodium 3alpha,12 alpha-dihydroxy-7-oxo-5 beta-cholanoate at
      concentration 0.9 CMC reached saturation level of 60% dissolved resveratrol. The
      curve for sodium dodecyl sulfate was linear within the whole range of the
      investigated concentration; resveratrol solubilization rate reached 13% at 2 CMC.
      In S7-OD, NaCl increased capacity of resveratrol solubilization up to 1.4 CMC
      surfactant concentration, whilst maximum level of dissolved resveratrol (90%) was
      observed at 0.9 CMC. In SDS, NaCl decreased resveratrol solubilization capacity.
      Urea reduced resveratrol solubilization rate in sodium 3alpha ,12 alpha-dihydroxy
      7-oxo-5 beta-cholanoate, whereas it had inverse effect in sodium dodecyl sulfate.
      The obtained results strongly suggest that structure, that is, shape, of the
      surfactant micelles significantly affects their capacity of resveratrol
      solubilization. Also, presence of NaCl and urea influences solubilization
      capacities of investigated surfactants.

PMID- 24688375
TI  - SFG synthesis of general high-order all-pass and all-pole current transfer
      functions using CFTAs.
AB  - An approach of using the signal flow graph (SFG) technique to synthesize general
      high-order all-pass and all-pole current transfer functions with current follower
      transconductance amplifiers (CFTAs) and grounded capacitors has been presented.
      For general nth-order systems, the realized all-pass structure contains at most n
      + 1 CFTAs and n grounded capacitors, while the all-pole lowpass circuit requires
      only n CFTAs and n grounded capacitors. The resulting circuits obtained from the
      synthesis procedure are resistor-less structures and especially suitable for
      integration. They also exhibit low-input and high-output impedances and also
      convenient electronic controllability through the g m-value of the CFTA.
      Simulation results using real transistor model parameters ALA400 are also
      included to confirm the theory.

PMID- 24688377
TI  - Formation of three-way scanning electron microscope moire on
      micro/nanostructures.
AB  - Three-way scanning electron microscope (SEM) moire was first generated using a
      designed three-way electron beam (EB) in an SEM. The spot-type three-way SEM
      moire comes from the interference between the three-way EB and the specimen
      grating in which the periodic cells are arranged in a triangular manner. The
      deformation and the structure information of the specimen grating in three
      directions can be simultaneously obtained from the three-way SEM moire. The
      design considerations of the three-way EB were discussed. As an illustration, the
      three-way SEM moire spots produced on a silicon slide were presented. The
      proposed three-way SEM moire method is expected to characterize
      micro/nanostructures in triangular or hexagonal arrangements in three directions
      at the same time. 

PMID- 24688376
TI  - Carrier-based drug delivery system for treatment of acne.
AB  - Approximately 95% of the population suffers at some point in their lifetime from
      acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This
      inflammatory skin disorder is most common in adolescents but also affects
      neonates, prepubescent children, and adults. Topical conventional systems are
      associated with various side effects. Novel drug delivery systems have been used
      to reduce the side effect of drugs commonly used in the topical treatment of
      acne. Topical treatment of acne with active pharmaceutical ingredients (API)
      makes direct contact with the target site before entering the systemic
      circulation which reduces the systemic side effect of the parenteral or oral
      administration of drug. The objective of the present review is to discuss the
      conventional delivery systems available for acne, their drawbacks, and
      limitations. The advantages, disadvantages, and outcome of using various carrier
      based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and
      so forth, are explained. This paper emphasizes approaches to overcome the
      drawbacks and limitations associated with the conventional system and the
      advances and application that are poised to further enhance the efficacy of
      topical acne formulations, offering the possibility of simplified dosing regimen
      that may improve treatment outcomes using novel delivery system. 

PMID- 24688378
TI  - On the number of spanning trees of graphs.
AB  - We establish some bounds for the number of spanning trees of connected graphs in
      terms of the number of vertices (n), the number of edges (m), maximum vertex
      degree (Delta1), minimum vertex degree (delta), first Zagreb index (M 1), and
      Randic index (R -1). 

PMID- 24688379
TI  - Performance analysis of MIMO-STBC systems with higher coding rate using adaptive
      semiblind channel estimation scheme.
AB  - Semiblind channel estimation method provides the best trade-off in terms of
      bandwidth overhead, computational complexity and latency. The result after using
      multiple input multiple output (MIMO) systems shows higher data rate and longer
      transmit range without any requirement for additional bandwidth or transmit
      power. This paper presents the detailed analysis of diversity coding techniques
      using MIMO antenna systems. Different space time block codes (STBCs) schemes have
      been explored and analyzed with the proposed higher code rate. STBCs with higher
      code rates have been simulated for different modulation schemes using MATLAB
      environment and the simulated results have been compared in the semiblind
      environment which shows the improvement even in highly correlated antenna arrays
      and is found very close to the condition when channel state information (CSI) is
      known to the channel. 

PMID- 24688381
TI  - q-Sumudu transforms of q-analogues of Bessel functions.
AB  - The main purpose of this paper is to evaluate q-Sumudu transforms of a product of
      q-Bessel functions. Interesting special cases of theorems are also discussed.
      Further, the results proved in this paper may find certain applications of q
      Sumudu transforms to the solutions of the q-integrodifferential equations
      involving q-Bessel functions. The results may help to extend the q-theory of
      orthogonal functions. 

PMID- 24688380
TI  - Atherosclerosis and atheroma plaque rupture: imaging modalities in the
      visualization of vasa vasorum and atherosclerotic plaques.
AB  - Invasive angiography has been widely accepted as the gold standard to diagnose
      cardiovascular pathologies. Despite its superior resolution of demonstrating
      atherosclerotic plaque in terms of degree of lumen stenosis, the morphological
      assessment for the plaque is insufficient for the analysis of plaque components,
      and therefore, unable to predict the risk status or vulnerability of
      atherosclerotic plaque. There is an increased body of evidence to show that the
      vasa vasorum play an important role in the initiation, progression, and
      complications of atherosclerotic plaque leading to major adverse cardiac events.
      This paper provides an overview of the evidence-based reviews of various imaging
      modalities with regard to their potential value for comprehensive
      characterization of the composition, burden, and neovascularization of
      atherosclerotic plaque. 

PMID- 24688382
TI  - Evaluation of arbuscular mycorrhizal fungi capacity to alleviate abiotic stress
      of olive (Olea europaea L.) plants at different transplant conditions.
AB  - The capacity of roots to sense soil physicochemical parameters plays an essential
      role in maintaining plant nutritional and developmental functions under abiotic
      stress. These conditions generate reactive oxygen species (ROS) in plant tissues
      causing oxidation of proteins and lipids among others. Some plants have developed
      adaptive mechanisms to counteract such adverse conditions such as symbiotic
      association with arbuscular mycorrhizal fungi (AMF). AMF enhance plant growth and
      improve transplant survival by protecting host plants against environmental
      stresses. The aim of this study was to evaluate the alleviation of transplanting
      stress by two strains of Rhizophagus irregularis (GC2 and GA5) in olive. Our
      results show that olive plants have an additional energetic expense in growth due
      to an adaptative response to the growing stage and to the mycorrhizal
      colonization at the first transplant. However, at the second transplant the
      coinoculation improves olive plant growth and protects against oxidative stress
      followed by the GA5-inoculation. In conclusion, a combination of two AMF strains
      at the beginning of olive propagation produces vigorous plants successfully
      protected in field cultivation even with an additional cost at the beginning of
      growth. 

PMID- 24688383
TI  - Phytase production by Aspergillus niger CFR 335 and Aspergillus ficuum SGA 01
      through submerged and solid-state fermentation.
AB  - Fermentation is one of the industrially important processes for the development
      of microbial metabolites that has immense applications in various fields. This
      has prompted to employ fermentation as a major technique in the production of
      phytase from microbial source. In this study, a comparison was made between
      submerged (SmF) and solid-state fermentations (SSF) for the production of phytase
      from Aspergillus niger CFR 335 and Aspergillus ficuum SGA 01. It was found that
      both the fungi were capable of producing maximum phytase on 5th day of incubation
      in both submerged and solid-state fermentation media. Aspergillus niger CFR 335
      and A. ficuum produced a maximum of 60.6 U/gds and 38 U/gds of the enzyme,
      respectively, in wheat bran solid substrate medium. Enhancement in the enzyme
      level (76 and 50.7 U/gds) was found when grown in a combined solid substrate
      medium comprising wheat bran, rice bran, and groundnut cake in the ratio of 2 : 1
      : 1. A maximum of 9.6 and 8.2 U/mL of enzyme activity was observed in SmF by A.
      niger CFR 335 and A.ficuum, respectively, when grown in potato dextrose broth.

PMID- 24688384
TI  - Biomedical informatics and computational biology for high-throughput data
      analysis.

PMID- 24688385
TI  - Effect of selenate on viability and selenomethionine accumulation of Chlorella
      sorokiniana grown in batch culture.
AB  - The aim of this work was to study the effect of Se(+VI) on viability, cell
      morphology, and selenomethionine accumulation of the green alga Chlorella
      sorokiniana grown in batch cultures. Culture exposed to sublethal Se
      concentrations of 40 mg . L(-1) (212 MUM) decreased growth rates for about 25%
      compared to control. A selenate EC50 value of 45 mg . L(-1) (238.2 MUM) was
      determined. Results showed that chlorophyll and carotenoids contents were not
      affected by Se exposure, while oxygen evolution decreased by half.
      Ultrastructural studies revealed granular stroma, fingerprint-like appearance of
      thylakoids which did not compromise cell activity. Unlike control cultures, SDS
      PAGE electrophoresis of crude extracts from selenate-exposed cell cultures
      revealed appearance of a protein band identified as 53 kDa Rubisco large subunit
      of Chlorella sorokiniana, suggesting that selenate affects expression of the
      corresponding chloroplast gene as this subunit is encoded in the chloroplast DNA.
      Results revealed that the microalga was able to accumulate up to 140 mg . kg(-1)
      of SeMet in 120 h of cultivation. This paper shows that Chlorella sorokiniana
      biomass can be enriched in the high value aminoacid SeMet in batch cultures,
      while keeping photochemical viability and carbon dioxide fixation activity
      intact, if exposed to suitable sublethal concentrations of Se.

PMID- 24688386
TI  - Discoloration of roots caused by residual endodontic intracanal medicaments.
AB  - AIMS: This study examined the extent to which intervisit corticosteroid-based
      antibiotic pastes (CAP) medicaments contribute to staining of tooth structure
      after attempted removal by irrigation techniques. METHODS: A total of 140 roots
      were prepared and the canals were filled with Ledermix paste (demeclocycline),
      Odontopaste (clindamycin), and Doxypaste (doxycycline). The pastes were removed
      after 2 or 4 weeks of storage in the dark using EDTA and NaOCl with either a 27
      gauge-slotted needle or an EndoActivator (Dentsply). The roots were then exposed
      to an intense light source for 30 minutes each week and photographed after a
      further 1, 3, or 6 months. Digital images were standardized and data for changes
      in luminosity were analysed using repeated measures ANOVA and a post hoc test.
      RESULTS: Removal of the medicament did not prevent later discolouration. There
      was no significant difference between the paste removal methods. Ledermix paste
      caused the greatest darkening compared to the untreated controls, for both
      application periods and both methods of removal. Doxypaste and Odontopaste caused
      less darkening than Ledermix. CONCLUSION: Medicaments that stain teeth may
      continue to discolour teeth despite best attempts to remove them. This study
      stresses the importance of material selection and minimising contact of Ledermix
      within the coronal aspects of teeth.

PMID- 24688387
TI  - An assessment of wound healing potential of Argyreia speciosa leaves.
AB  - In North India, poultice of young unfolded leaves of Argyreia speciosa Linn.
      (Convolvulaceae) is used for healing wounds. In order to find scientific evidence
      for the traditional utilization of leaves of A. speciosa in wound healing, this
      investigation was carried out. A linear incision wound of about 3 cm in length
      and 2 mm in depth and circular excision wound of 177 mm(2) full thickness were
      made on the dorsal region of separate groups (n = 5) of anesthetized Swiss albino
      mice. A simple ointment, developed by including ethanol, ethanol-water, and water
      extracts (10% each, separately) of A. speciosa, was applied topically to mice
      once daily for 14 days after wounding. To evaluate the effect of each extract,
      wound contraction, epithelization period, wound breaking strength, and
      hydroxyproline content were determined. The water extract of A. speciosa showed
      accelerated wound healing activity as evidenced by fast wound contraction (96.30
      +/- 0.52%; P < 0.01), rapid epithelization period (11.40 +/- 0.60 days; P <
      0.001), greater wound breaking strength (376.56 +/- 21.16 g; P < 0.001), and
      higher hydroxyproline content (16.49 +/- 1.12 mg/g; P < 0.05) of granulation
      tissue. The present report supports the traditional use of Argyreia speciosa
      leaves for wound healing and signify its relevant therapeutic potential.

PMID- 24688388
TI  - Optimized liquid-liquid extractive rerefining of spent lubricants.
AB  - Central composite design methodology has been employed to model the sludge yield
      data obtained during liquid-liquid extractive rerefining of spent lubricants
      using an alcohol (1-butanol) and a ketone (methyl ethyl ketone) as prospective
      solvents. The study has resulted in two reasonably accurate multivariate process
      models that relate the sludge yield (R (2) = 0.9065 and 0.9072 for alcohol and
      ketone, resp.) to process variables (settling time t, operating temperature T,
      and oil to solvent ratio r). Construction of such models has allowed the
      maximization of the sludge yield (more than 8% and 3% in case of alcohol and
      ketone, resp.) so that the extraction of useable oil components from spent
      lubricants can economically be performed under extremely mild conditions (t =
      16.7 h, T = 10 degrees C, and r = 2) and fairly moderate conditions (t = 26.6 h,
      T = 10 degrees C, and r = 5) established for the alcohol and ketone
      correspondingly. Based on these performance parameters alcohol appears to be
      superior over ketone for this extraction process. Additionally extractive
      treatment results in oil stocks with lesser quantity of environmentally hazardous
      polyaromatic hydrocarbons that are largely left in the separated sludge.

PMID- 24688389
TI  - A modified decision tree algorithm based on genetic algorithm for mobile user
      classification problem.
AB  - In order to offer mobile customers better service, we should classify the mobile
      user firstly. Aimed at the limitations of previous classification methods, this
      paper puts forward a modified decision tree algorithm for mobile user
      classification, which introduced genetic algorithm to optimize the results of the
      decision tree algorithm. We also take the context information as a classification
      attributes for the mobile user and we classify the context into public context
      and private context classes. Then we analyze the processes and operators of the
      algorithm. At last, we make an experiment on the mobile user with the algorithm,
      we can classify the mobile user into Basic service user, E-service user, Plus
      service user, and Total service user classes and we can also get some rules about
      the mobile user. Compared to C4.5 decision tree algorithm and SVM algorithm, the
      algorithm we proposed in this paper has higher accuracy and more simplicity. 

PMID- 24688390
TI  - Overexpression of a Vesicle Trafficking Gene, OsRab7, enhances salt tolerance in
      rice.
AB  - High soils salinity is a main factor affecting agricultural production. Studying
      the function of salt-tolerance-related genes is essential to enhance crop
      tolerance to stress. Rab7 is a small GTP-binding protein that is distributed
      widely among eukaryotes. Endocytic trafficking mediated by Rab7 plays an
      important role in animal and yeast cells, but the current understanding of Rab7
      in plants is still very limited. Herein, we isolated a vesicle trafficking gene,
      OsRab7, from rice. Transgenic rice over-expressing OsRab7 exhibited enhanced
      seedling growth and increased proline content under salt-treated conditions.
      Moreover, an increased number of vesicles was observed in the root tip of OsRab7
      transgenic rice. The OsRab7 over-expression plants showed enhanced tolerance to
      salt stress, suggesting that vacuolar trafficking is important for salt tolerance
      in plants. 

PMID- 24688392
TI  - Explicit finite difference methods for the delay pseudoparabolic equations.
AB  - Finite difference technique is applied to numerical solution of the initial
      boundary value problem for the semilinear delay Sobolev or pseudoparabolic
      equation. By the method of integral identities two-level difference scheme is
      constructed. For the time integration the implicit rule is being used. Based on
      the method of energy estimates the fully discrete scheme is shown to be
      absolutely stable and convergent of order two in space and of order one in time.
      The error estimates are obtained in the discrete norm. Some numerical results
      confirming the expected behavior of the method are shown. 

PMID- 24688391
TI  - Physician awareness of knee and hip pain in the context of coronary heart disease
      treatment.
AB  - BACKGROUND: The benefit of physical activity for the prevention and treatment of
      cardiovascular disease (CVD) has been well documented. The aim of the present
      study was to determine the level of awareness among general practitioners (GPs)
      of knee and hip problems in patients with CVD or CVD risk. DESIGN: Cross
      sectional questionnaire survey. SETTING AND SUBJECTS: Thirty-five Austrian GPs
      and 1,118 patients were included. The GPs completed an extraction form about the
      presence or absence of documented evidence of problems related to the knee and/or
      hip joint within the patient medical data. Patients, in turn, were asked to
      complete a questionnaire that included the Oxford Knee/Hip Score and the
      cardiovascular risk-chart established by the European Society of Cardiology.
      RESULTS: In 748 patients' data from medical records and questionnaires were
      available. 40.9% of these patients suffered from serious knee pain and 32.1% from
      hip pain. However, in the medical records, in only 51.3% (knee) and 48.1% (hip)
      of these pain-patients the problems were documented. CONCLUSION: Joint disorders
      of the knee and hip problems are considerable barriers to effective physical
      activity and can therefore contribute to the development of CVD. Our data showed
      that GP awareness of such knee/hip disorders should be improved.

PMID- 24688393
TI  - Do we need to clamp the renal hilum liberally during the initial phase of the
      learning curve of robot-assisted nephron-sparing surgery?
AB  - OBJECTIVE: We aimed to compare the results of our initial robot-assisted nephron
      sparing surgeries (RANSS) performed with or without hilar clamping. MATERIAL AND
      METHOD: Charts of the initial RANSSs (n = 44), which were performed by a single
      surgeon, were retrospectively reviewed. R.E.N.A.L. nephrometry system, modified
      Clavien classification, and M.D.R.D. equation were used to record tumoral
      complexity, complications, and estimated glomerular filtration rate (eGFR),
      respectively. Outcomes of the clamped (group 1, n = 14) versus off-clamp (group
      2, n = 30) RANSSs were compared. RESULTS: The difference between the two groups
      was insignificant regarding mean patient age, mean tumor size, and mean
      R.E.N.A.L. nephrometry score. Mean operative time, mean estimated blood loss
      amount, and mean length of hospitalization were similar between groups. A total
      of 4 patients in each group suffered 11 Clavien grade >= 2 complications early
      postoperatively. Open conversion rates were similar. The difference between the 2
      groups in terms of the mean postoperative change in eGFR was insignificant. We
      did not encounter any local recurrence after a mean follow-up of 18.9 months.
      CONCLUSIONS: Creating warm-ischemic conditions during RANSS should not be a
      liberal decision, even in the initial phases of the learning curve for a highly
      experienced open surgeon.

PMID- 24688395
TI  - Cephalic index in the first three years of life: study of children with normal
      brain development based on computed tomography.
AB  - Cephalic index is a highly useful method for planning surgical procedures, as
      well as assessing their effectiveness in correcting cranial deformations in
      children. There are relatively very few studies measuring cephalic index in
      healthy Caucasian young children. The aim of our study was to develop a
      classification of current cephalic index for healthy Caucasian children up to 3
      years of age with normal brain development, using axial slice computer tomography
      performed with very thin slices (0.5 mm) resulting in more accurate measurements.
      180 healthy infants (83 females and 97 males) were divided into 5 age categories:
      0-3, 4-6, 7-12, 13-24, and 25-36 months. The average value of cephalic index in
      children up to 3 years of age amounted to 81.45 +/- 7.06. The index value in case
      of children under 3 months was 80.19, 4 to 6 months was 81.45, 7 to 12 months was
      83.15, in children under 2 years was 81.05, and in children under 3 years was
      79.76. Mesocephaly is the dominating skull shape in children. In this study, we
      formulated a classification of current cephalic indices of children with normal
      brain development. Our date appears to be of utmost importance in anthropology,
      anatomy forensic medicine, and genetics.

PMID- 24688394
TI  - Cochlear implant programming: a global survey on the state of the art.
AB  - The programming of CIs is essential for good performance. However, no Good
      Clinical Practice guidelines exist. This paper reports on the results of an
      inventory of the current practice worldwide. A questionnaire was distributed to
      47 CI centers. They follow 47600 recipients in 17 countries and 5 continents. The
      results were discussed during a debate. Sixty-two percent of the results were
      verified through individual interviews during the following months. Most centers
      (72%) participated in a cross-sectional study logging 5 consecutive fitting
      sessions in 5 different recipients. Data indicate that general practice starts
      with a single switch-on session, followed by three monthly sessions, three
      quarterly sessions, and then annual sessions, all containing one hour of
      programming and testing. The main focus lies on setting maximum and, to a lesser
      extent, minimum current levels per electrode. These levels are often determined
      on a few electrodes and then extrapolated. They are mainly based on subjective
      loudness perception by the CI user and, to a lesser extent, on pure tone and
      speech audiometry. Objective measures play a small role as indication of the
      global MAP profile. Other MAP parameters are rarely modified. Measurable targets
      are only defined for pure tone audiometry. Huge variation exists between centers
      on all aspects of the fitting practice. 

PMID- 24688396
TI  - Fabrication of ZnS-Bi-TiO2 composites and investigation of their sunlight
      photocatalytic performance.
AB  - The ZnS-Bi-TiO2 composites were prepared by the sol-gel method and were
      characterized by X-ray photoelectron spectroscopy (XPS), transmission electron
      microscopy (TEM), X-ray diffraction (XRD) and UV-visible diffuse reflectance
      spectroscopy (UV-Vis DRS). It is found that the doped Bi as Bi(4+)/Bi(3+) species
      existed in composites, and the introducing of ZnS enhanced further the light
      absorption ability of TiO2 in visible region and reduced the recombination of
      photogenerated electrons and holes. As compared to pure TiO2, the ZnS-Bi-TiO2
      exhibited enhanced photodegradation efficiency under xenon lamp irradiation, and
      the kinetic constant of methyl orange removal with ZnS-Bi-Ti-0.005 (0.0141 min(
      1)) was 3.9 times greater than that of pure TiO2 (0.0029 min(-1)), which could be
      attributed to the existence of Bi(4+)/Bi(3+) species, the ZnS/TiO2
      heterostructure.

PMID- 24688397
TI  - Normal values of metatarsal parabola arch in male and female feet.
AB  - There is not any method to measure metatarsal protrusion in the whole metatarsal.
      The aim of this research is to know the normal metatarsal parabola in male and
      female feet. The system of measurement devised by Hardy and Clapham to evaluate
      the protrusion between metatarsals I and II was adapted to study the whole
      metatarsal parabola and applied to the five metatarsals of 169 normal feet, 72
      female feet and 97 male feet. Authors measured all metatarsal protrusion relative
      to metatarsal II. The results obtained show a female metatarsal protrusion
      relative to metatarsal II of +1.27% for metatarsal I, -3.36% for metatarsal III, 
      8.34% for metatarsal IV, and -15.54% for metatarsal V. Data obtained for male
      metatarsal parabola were +0.5% for metatarsal I, -3.77 for metatarsal III, -9.57
      for metatarsal IV, and -17.05 for metatarsal V. Differences between both
      metatarsal parabola were significant. 

PMID- 24688398
TI  - A TOTP-based enhanced route optimization procedure for mobile IPv6 to reduce
      handover delay and signalling overhead.
AB  - Due to the proliferation of handheld mobile devices, multimedia applications like
      Voice over IP (VoIP), video conferencing, network music, and online gaming are
      gaining popularity in recent years. These applications are well known to be delay
      sensitive and resource demanding. The mobility of mobile devices, running these
      applications, across different networks causes delay and service disruption.
      Mobile IPv6 was proposed to provide mobility support to IPv6-based mobile nodes
      for continuous communication when they roam across different networks. However,
      the Route Optimization procedure in Mobile IPv6 involves the verification of
      mobile node's reachability at the home address and at the care-of address (home
      test and care-of test) that results in higher handover delays and signalling
      overhead. This paper presents an enhanced procedure, time-based one-time password
      Route Optimization (TOTP-RO), for Mobile IPv6 Route Optimization that uses the
      concepts of shared secret Token, time based one-time password (TOTP) along with
      verification of the mobile node via direct communication and maintaining the
      status of correspondent node's compatibility. The TOTP-RO was implemented in
      network simulator (NS-2) and an analytical analysis was also made. Analysis
      showed that TOTP-RO has lower handover delays, packet loss, and signalling
      overhead with an increased level of security as compared to the standard Mobile
      IPv6's Return-Routability-based Route Optimization (RR-RO). 

PMID- 24688399
TI  - Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic
      fatty liver disease in rats.
AB  - Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising
      globally with current upsurge in obesity, is one of the most frequent causes of
      chronic liver diseases. The present study evaluated the ameliorative effect of
      extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced
      NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose
      levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all
      tested dose levels significantly attenuated the pathological alterations
      associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and
      lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as
      well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly
      reduced body weight and adiposity along with an improvement in insulin resistance
      index. The study findings, therefore suggested the therapeutic potential of ETS
      against NAFLD, acting in part through antiobesity, insulin sensitizing, and
      antioxidant mechanisms.

PMID- 24688400
TI  - Prediction of frequency for simulation of asphalt mix fatigue tests using MARS
      and ANN.
AB  - Fatigue life of asphalt mixes in laboratory tests is commonly determined by
      applying a sinusoidal or haversine waveform with specific frequency. The pavement
      structure and loading conditions affect the shape and the frequency of tensile
      response pulses at the bottom of asphalt layer. This paper introduces two methods
      for predicting the loading frequency in laboratory asphalt fatigue tests for
      better simulation of field conditions. Five thousand (5000) four-layered pavement
      sections were analyzed and stress and strain response pulses in both longitudinal
      and transverse directions was determined. After fitting the haversine function to
      the response pulses by the concept of equal-energy pulse, the effective length of
      the response pulses were determined. Two methods including Multivariate Adaptive
      Regression Splines (MARS) and Artificial Neural Network (ANN) methods were then
      employed to predict the effective length (i.e., frequency) of tensile stress and
      strain pulses in longitudinal and transverse directions based on haversine
      waveform. It is indicated that, under controlled stress and strain modes, both
      methods (MARS and ANN) are capable of predicting the frequency of loading in HMA
      fatigue tests with very good accuracy. The accuracy of ANN method is, however,
      more than MARS method. It is furthermore shown that the results of the present
      study can be generalized to sinusoidal waveform by a simple equation. 

PMID- 24688401
TI  - Effect of strength enhancement of soil treated with environment-friendly calcium
      carbonate powder.
AB  - This study aims to investigate the effects of the strength improvement of soft
      ground (sand) by producing calcium carbonate powder through microbial reactions.
      To analyze the cementation effect of calcium carbonate produced through microbial
      reaction for different weight ratios, four different types of specimens
      (untreated, calcium carbonate, cement, and calcium carbonate + cement) with
      different weight ratios (2%, 4%, 6%, and 8%) were produced and cured for a period
      of 3 days, 7 days, 14 days, 21 days, and 28 days to test them. The uniaxial
      compression strength of specimens was measured, and the components in the
      specimen depending on the curing period were analyzed by means of XRD analysis.
      The result revealed that higher weight ratios and longer curing period
      contributed to increased strength of calcium carbonate, cement, and calcium
      carbonate + cement specimens. The calcium carbonate and the calcium carbonate +
      cement specimens in the same condition showed the tendency of decreased strength
      approximately 3 times and two times in comparison with the 8% cement specimens
      cured for 28 days, but the tendency of increased strength was approximately 4
      times and 6 times in comparison with the untreated specimen. 

PMID- 24688402
TI  - Performance of diesel engine using diesel B3 mixed with crude palm oil.
AB  - The objective of this study was to test the performance of diesel engine using
      diesel B3 mixed with crude palm oil in ratios of 95 : 5, 90 : 10, and 85 : 15,
      respectively, and to compare the results with diesel B3. According to the tests,
      they showed that the physical properties of the mixed fuel in the ratio of 95 : 5
      were closest to those of diesel B3. The performance of the diesel engine that
      used mixed fuels had 5-17% lower torque and power than that of diesel B3. The
      specific fuel consumption of mixed fuels was 7-33% higher than using diesel B3.
      The components of gas emissions by using mixed fuel had 1.6-52% fewer amount of
      carbon monoxide (CO), carbon dioxide (CO2), sulfur dioxide (SO2), and oxygen (O2)
      than those of diesel B3. On the other hand, nitric oxide (NO) and nitrogen oxides
      (NO X ) emissions when using mixed fuels were 10-39% higher than diesel B3. By
      comparing the physical properties, the performance of the engine, and the amount
      of gas emissions of mixed fuel, we found out that the 95 : 5 ratio by volume was
      a suitable ratio for agricultural diesel engine (low-speed diesel engine).

PMID- 24688403
TI  - On (Deltam, I)-statistical convergence of order alpha.
AB  - The idea of I-convergence of real sequences was introduced by Kostyrko et al.,
      (2000/01) and also independently by Nuray and Ruckle (2000). In this paper, we
      introduce the concepts of (Delta(m), I)-statistical convergence of order alpha
      and strong (Delta(p)(m), I)-Cesaro summability of order alpha of real sequences
      and investigated their relationship.

PMID- 24688404
TI  - Experiments in computing: a survey.
AB  - Experiments play a central role in science. The role of experiments in computing
      is, however, unclear. Questions about the relevance of experiments in computing
      attracted little attention until the 1980s. As the discipline then saw a push
      towards experimental computer science, a variety of technically, theoretically,
      and empirically oriented views on experiments emerged. As a consequence of those
      debates, today's computing fields use experiments and experiment terminology in a
      variety of ways. This paper analyzes experimentation debates in computing. It
      presents five ways in which debaters have conceptualized experiments in
      computing: feasibility experiment, trial experiment, field experiment, comparison
      experiment, and controlled experiment. This paper has three aims: to clarify
      experiment terminology in computing; to contribute to disciplinary self
      understanding of computing; and, due to computing's centrality in other fields,
      to promote understanding of experiments in modern science in general. 

PMID- 24688405
TI  - A statistical approach to optimizing concrete mixture design.
AB  - A step-by-step statistical approach is proposed to obtain optimum proportioning
      of concrete mixtures using the data obtained through a statistically planned
      experimental program. The utility of the proposed approach for optimizing the
      design of concrete mixture is illustrated considering a typical case in which
      trial mixtures were considered according to a full factorial experiment design
      involving three factors and their three levels (3(3)). A total of 27 concrete
      mixtures with three replicates (81 specimens) were considered by varying the
      levels of key factors affecting compressive strength of concrete, namely,
      water/cementitious materials ratio (0.38, 0.43, and 0.48), cementitious materials
      content (350, 375, and 400 kg/m(3)), and fine/total aggregate ratio (0.35, 0.40,
      and 0.45). The experimental data were utilized to carry out analysis of variance
      (ANOVA) and to develop a polynomial regression model for compressive strength in
      terms of the three design factors considered in this study. The developed
      statistical model was used to show how optimization of concrete mixtures can be
      carried out with different possible options.

PMID- 24688406
TI  - A dual-mode bandpass filter with multiple controllable transmission-zeros using T
      shaped stub-loaded resonators.
AB  - A dual-mode broadband bandpass filter (BPF) with multiple controllable
      transmission-zeros using T-shaped stub-loaded resonators (TSSLRs) is presented.
      Due to the symmetrical plane, the odd-even-mode theory can be adopted to
      characterize the BPF. The proposed filter consists of a dual-mode TSSLR and two
      modified feed-lines, which introduce two capacitive and inductive source-load (S
      L) couplings. Five controllable transmission zeros (TZs) can be achieved for the
      high selectivity and the wide stopband because of the tunable amount of coupling
      capacitance and inductance. The center frequency of the proposed BPF is 5.8 GHz,
      with a 3 dB fraction bandwidth of 8.9%. The measured insertion and return losses
      are 1.75 and 28.18 dB, respectively. A compact size and second harmonic frequency
      suppression can be obtained by the proposed BPF with S-L couplings.

PMID- 24688407
TI  - EPDM based double slope triangular enclosure solar collector: a novel approach.
AB  - Solar heating is one of the important utilities of solar energy both in domestic
      and industrial sectors. Evacuated tube heaters are a commonly used technology for
      domestic water heating. However, increasing cost of copper and nickel has
      resulted in huge initial cost for these types of heaters. Utilizing solar energy
      more economically for domestic use requires new concept which has low initial and
      operating costs together with ease of maintainability. As domestic heating
      requires only nominal heating temperature to the range of 60-90  degrees C,
      therefore replacing nickel coated copper pipes with any cheap alternate can
      drastically reduce the cost of solar heater. We have proposed a new concept which
      utilizes double slope triangular chamber with EPDM based synthetic rubber pipes.
      This has reduced the initial and operating costs substantially. A detailed
      analytical study was carried out to design a novel solar heater. On the basis of
      analytical design, a prototype was manufactured. Results obtained from the
      experiments were found to be in good agreement with the analytical study. A
      maximum error of 10% was recorded at noon. However, results show that error is
      less than 5% in early and late hours.

PMID- 24688409
TI  - Effects of thapsigargin on the proliferation and survival of human rheumatoid
      arthritis synovial cells.
AB  - A series of experiments have been carried out to investigate the effects of
      different concentrations of thapsigargin (0, 0.001, 0.1, and 1 MUM) on the
      proliferation and survival of human rheumatoid arthritis synovial cells (MH7A).
      The results showed that thapsigargin can block the cell proliferation in human
      rheumatoid arthritis synovial cells in a time- and dose-dependent manner. Results
      of Hoechst staining suggested that thapsigargin may induce cell apoptosis in MH7A
      cells in a time- and dose-dependent manner, and the percentages of cell death
      reached 44.6% at thapsigargin concentration of 1 MUM treated for 4 days compared
      to the control. The protein and mRNA levels of cyclin D1 decreased gradually with
      the increasing of thapsigargin concentration and treatment times. Moreover, the
      protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by
      thapsigargin treatment at different concentrations and times, which should be
      responsible for the reduced cyclin D1 expressions. Our results revealed that
      thapsigargin may effectively impair the cell proliferation and survival of MH7A
      cells. The present findings will help to understand the molecular mechanism of
      fibroblast-like synoviocytes proliferations and suggest that thapsigargin is of
      potential for the clinical treatment of rheumatoid arthritis.

PMID- 24688408
TI  - Comparison of protein acetyltransferase action of CRTAase with the prototypes of
      HAT.
AB  - Our laboratory is credited for the discovery of enzymatic acetylation of protein,
      a phenomenon unknown till we identified an enzyme termed acetoxy drug: protein
      transacetylase (TAase), catalyzing the transfer of acetyl group from polyphenolic
      acetates to receptor proteins (RP). Later, TAase was identified as calreticulin
      (CR), an endoplasmic reticulum luminal protein. CR was termed calreticulin
      transacetylase (CRTAase). Our persistent study revealed that CR like other
      families of histone acetyltransferases (HATs) such as p300, Rtt109, PCAF, and
      ESA1, undergoes autoacetylation. The autoacetylated CR was characterized as a
      stable intermediate in CRTAase catalyzed protein acetylation, and similar was the
      case with ESA1. The autoacetylation of CR like that of HATs was found to enhance
      protein-protein interaction. CR like HAT-1, CBP, and p300 mediated the acylation
      of RP utilizing acetyl CoA and propionyl CoA as the substrates. The similarities
      between CRTAase and HATs in mediating protein acylation are highlighted in this
      review.

PMID- 24688411
TI  - A comprehensive robust adaptive controller for gust load alleviation.
AB  - The objective of this paper is the implementation and validation of an adaptive
      controller for aircraft gust load alleviation. The contribution of this paper is
      the design of a robust controller that guarantees the reduction of the gust
      loads, even when the nominal conditions change. Some preliminary results are
      presented, considering the symmetric aileron deflection as control device. The
      proposed approach is validated on subsonic transport aircraft for different mass
      and flight conditions. Moreover, if the controller parameters are tuned for a
      specific gust model, even if the gust frequency changes, no parameter retuning is
      required. 

PMID- 24688410
TI  - Emerging persistent organic pollutants in Chinese Bohai Sea and its coastal
      regions.
AB  - Emerging persistent organic pollutants (POPs) have widely aroused public concern
      in recent years. Polybrominated diphenyl ethers (PBDEs) and perfluorooctane
      sulfonyl fluoride/perfluorooctane sulfonic acid (POSF/PFOS) had been newly listed
      in Stockholm Convention in 2009, and short chain chlorinated paraffins (SCCPs)
      and hexabromocyclododecanes (HBCDs) were listed as candidate POPs. Bohai Sea is
      located in the arms of numbers of industrial cities, the semienclosed location of
      which makes it an ideal sink of emerging pollutants. In the present paper, latest
      contamination status of emerging POPs in Bohai Sea was reviewed. According to the
      literature data, Bohai Sea areas are not heavily contaminated by emerging POPs
      (PBDE: 0.01-720 ng/g; perfluorinated compounds: 0.1-304 ng/g; SCCPs: 64.9-5510
      ng/g; HBCDs: nd-634 ng/g). Therefore, humans are not likely to be under serious
      risk of emerging POPs exposure through consuming seafood from Bohai Sea. However,
      the ubiquitous occurrence of emerging POPs in Bohai Sea region might indicate
      that more work should be done to expand the knowledge about potential risk of
      emerging POPs pollution.

PMID- 24688412
TI  - A stochastic total least squares solution of adaptive filtering problem.
AB  - An efficient and computationally linear algorithm is derived for total least
      squares solution of adaptive filtering problem, when both input and output
      signals are contaminated by noise. The proposed total least mean squares (TLMS)
      algorithm is designed by recursively computing an optimal solution of adaptive
      TLS problem by minimizing instantaneous value of weighted cost function.
      Convergence analysis of the algorithm is given to show the global convergence of
      the proposed algorithm, provided that the stepsize parameter is appropriately
      chosen. The TLMS algorithm is computationally simpler than the other TLS
      algorithms and demonstrates a better performance as compared with the least mean
      square (LMS) and normalized least mean square (NLMS) algorithms. It provides
      minimum mean square deviation by exhibiting better convergence in misalignment
      for unknown system identification under noisy inputs. 

PMID- 24688413
TI  - Design and control of an embedded vision guided robotic fish with multiple
      control surfaces.
AB  - This paper focuses on the development and control issues of a self-propelled
      robotic fish with multiple artificial control surfaces and an embedded vision
      system. By virtue of the hybrid propulsion capability in the body plus the caudal
      fin and the complementary maneuverability in accessory fins, a synthesized
      propulsion scheme including a caudal fin, a pair of pectoral fins, and a pelvic
      fin is proposed. To achieve flexible yet stable motions in aquatic environments,
      a central pattern generator- (CPG-) based control method is employed. Meanwhile,
      a monocular underwater vision serves as sensory feedback that modifies the
      control parameters. The integration of the CPG-based motion control and the
      visual processing in an embedded microcontroller allows the robotic fish to
      navigate online. Aquatic tests demonstrate the efficacy of the proposed
      mechatronic design and swimming control methods. Particularly, a pelvic fin
      actuated sideward swimming gait was first implemented. It is also found that the
      speeds and maneuverability of the robotic fish with coordinated control surfaces
      were largely superior to that of the swimming robot propelled by a single control
      surface. 

PMID- 24688414
TI  - Effects of subchronic exposure of diclofenac on growth, histopathological
      changes, and oxidative stress in zebrafish (Danio rerio).
AB  - The aim of this study was to investigate effects of subchronic exposure to
      sublethal levels of diclofenac on growth, oxidative stress, and histopathological
      changes in Danio rerio. The juvenile growth tests were performed on Danio rerio
      according to OECD method number 215. Fish at the age of 20 days were exposed to
      the diclofenac environmental concentration commonly detected in the Czech rivers
      (0.02 mg L(-1)) and the range of sublethal concentrations of diclofenac (5, 15,
      30, and 60 mg L(-1)) for 28 days. A significant decrease (P < 0.01) in the fish
      growth caused by diclofenac was observed in the concentrations of 30 and 60 mg L(
      1). The identified value of LOEC (lowest observed effect concentration) was 15 mg
      L(-1) of diclofenac and NOEC (no observed effect concentration) value was 5 mg L(
      1) of diclofenac. We did not find histopathological changes and changes of
      selected parameters of oxidative stress (glutathione S-transferase, glutathione
      reductase) in tested fish. The environmental concentration of diclofenac in Czech
      rivers did not have any effect on growth, selected oxidative stress parameters
      (glutathione S-transferase, glutathione reductase), or histopathological changes
      in Danio rerio but it could have an influence on lipid peroxidation.

PMID- 24688415
TI  - Effects of zoledronic acid on physiologic bone remodeling of condylar part of
      TMJ: a radiologic and histomorphometric examination in rabbits.
AB  - OBJECTIVE: The purpose of the present study is to evaluate the effects of
      systemically administered zoledronic acid (ZA) on the physiological bone
      remodeling and the microarchitectural parameters of the condylar part of TMJ in a
      rabbit model. STUDY DESIGN: Thirty skeletally mature male New Zealand white
      rabbits were randomly divided into two groups. The experimental group was
      administered an intravenous, single dose of 0.1 mg/kg ZA diluted with 15 mL of
      saline in a 15-minute perfusion with an infusion pump. The control group was
      administered only saline infusion for 15 minutes. All rabbits were sacrificed on
      the 21st postoperative day. Radiodensitometric and histomorphometric examinations
      were performed on the harvested mandibular condyles. The data were analyzed
      statistically. RESULTS: Radiodensitometric findings showed that ZA treatment
      resulted in a significant increase in the mineralization of mandibular condyle.
      This result was supported by the histomorphometric findings. CONCLUSION: The
      present study has revealed that a temporary delay in the physiological bone
      remodeling using single dose of ZA increases bone mineral content and makes the
      microarchitecture of the mandibular condyle more compact. These effects may be
      regarded as base data and considered in numerous clinical situations including
      TMJ.

PMID- 24688416
TI  - In-plane vibration analysis of annular plates with arbitrary boundary conditions.
AB  - In comparison with the out-of-plane vibrations of annular plates, far less
      attention has been paid to the in-plane vibrations which may also play a vital
      important role in affecting the sound radiation from and power flows in a built
      up structure. In this investigation, a generalized Fourier series method is
      proposed for the in-plane vibration analysis of annular plates with arbitrary
      boundary conditions along each of its edges. Regardless of the boundary
      conditions, the in-plane displacement fields are invariantly expressed as a new
      form of trigonometric series expansions with a drastically improved convergence
      as compared with the conventional Fourier series. All the unknown expansion
      coefficients are treated as the generalized coordinates and determined using the
      Rayleigh-Ritz technique. Unlike most of the existing studies, the presented
      method can be readily and universally applied to a wide spectrum of in-plane
      vibration problems involving different boundary conditions, varying material, and
      geometric properties with no need of modifying the basic functions or adapting
      solution procedures. Several numerical examples are presented to demonstrate the
      effectiveness and reliability of the current solution for predicting the in-plane
      vibration characteristics of annular plates subjected to different boundary
      conditions. 

PMID- 24688417
TI  - Skeletal muscle mass indices in healthy young Mexican adults aged 20-40 years:
      implications for diagnoses of sarcopenia in the elderly population.
AB  - BACKGROUND AND OBJECTIVES: Skeletal muscle and skeletal muscle indices in young
      adults from developing countries are sparse. Indices and the corresponding cut
      off points can be a reference for diagnoses of sarcopenia. This study assessed
      skeletal muscle using dual-energy X-ray absorptiometry (DXA) in healthy male and
      female subjects aged 20-40 years and compared their appendicular skeletal muscle
      mass (ASM) and total-body skeletal muscle (TBSM) indices using certain cut-off
      points published in the literature. METHODS: A sample of 216 healthy adults men
      and women from northwest Mexico was included. Body composition was assessed by
      DXA and several published DXA-derived skeletal muscle indices were compared.
      RESULTS: Both, ASM and TBSM were higher in men compared to the women group (23.0
      +/- 3.4 versus 15.9 +/- 1.6 kg; P < 0.05 and 26.5 +/- 4.1 versus 16.9 +/- 1.9 kg;
      P < 0.05, resp.). These differences were also valid for both indices. When
      derived cut-off points were compared with the most reported indices, significant
      differences were found. INTERPRETATION AND CONCLUSION: Published cut-off points
      from Caucasians are higher than cut-off point derived in this sample of Mexican
      subjects. The new DXA-derived cut-off points for ASM proposed herein may improve
      diagnoses of sarcopenia in the geriatric Mexican population.

PMID- 24688418
TI  - Articulated arm coordinate measuring machine calibration by laser tracker
      multilateration.
AB  - A new procedure for the calibration of an articulated arm coordinate measuring
      machine (AACMM) is presented in this paper. First, a self-calibration algorithm
      of four laser trackers (LTs) is developed. The spatial localization of a
      retroreflector target, placed in different positions within the workspace, is
      determined by means of a geometric multilateration system constructed from the
      four LTs. Next, a nonlinear optimization algorithm for the identification
      procedure of the AACMM is explained. An objective function based on Euclidean
      distances and standard deviations is developed. This function is obtained from
      the captured nominal data (given by the LTs used as a gauge instrument) and the
      data obtained by the AACMM and compares the measured and calculated coordinates
      of the target to obtain the identified model parameters that minimize this
      difference. Finally, results show that the procedure presented, using the
      measurements of the LTs as a gauge instrument, is very effective by improving the
      AACMM precision. 

PMID- 24688419
TI  - New green polymeric composites based on hemp and natural rubber processed by
      electron beam irradiation.
AB  - A new polymeric composite based on natural rubber reinforced with hemp has been
      processed by electron beam irradiation and characterized by several methods. The
      mechanical characteristics: gel fraction, crosslink density, water uptake,
      swelling parameters, and FTIR of natural rubber/hemp fiber composites have been
      investigated as a function of the hemp content and absorbed dose. Physical and
      mechanical properties present a significant improvement as a result of adding
      hemp fibres in blends. Our experiments showed that the hemp fibers have a
      reinforcing effect on natural rubber similar to mineral fillers (chalk, carbon
      black, silica). The crosslinking rates of samples, measured using the Flory
      Rehner equation, increase as a result of the amount of hemp in blends and the
      electron beam irradiation dose increasing. The swelling parameters of samples
      significantly depend on the amount of hemp in blends, because the latter have
      hydrophilic characteristics. 

PMID- 24688420
TI  - Masquelet technique for treatment of posttraumatic bone defects.
AB  - Masquelet technique, which is the use of a temporary cement spacer followed by
      staged bone grafting, is a recent treatment strategy to manage a posttraumatic
      bone defect. This paper describes a series of 9 patients treated with this
      technique of staged bone grafting following placement of an antibiotic spacer to
      successfully manage osseous long bone defects. The injured limbs were stabilized
      and aligned at the time of initial spacer placement. In our series, osseous
      consolidation was successfully achieved in all cases. This technique gives
      promising result in the management of posttraumatic bone defects. 

PMID- 24688421
TI  - Mechanical and morphological properties of polypropylene/nano alpha-Al2O3
      composites.
AB  - A nanocomposite containing polypropylene (PP) and nano alpha-Al2O3 particles was
      prepared using a Haake internal mixer. Mechanical tests, such as tensile and
      flexural tests, showed that mechanical properties of the composite were enhanced
      by addition of nano alpha-Al2O3 particles and dispersant agent to the polymer.
      Tensile strength was approximately ~ 16% higher than pure PP by increasing the
      nano alpha-Al2O3 loading from 1 to 4 wt% into the PP matrix. The results of
      flexural analysis indicated that the maximum values of flexural strength and
      flexural modulus for nanocomposite without dispersant were 50.5 and 1954 MPa and
      for nanocomposite with dispersant were 55.88 MPa and 2818 MPa, respectively.
      However, higher concentration of nano alpha-Al2O3 loading resulted in reduction
      of those mechanical properties that could be due to agglomeration of nano alpha
      Al2O3 particles. Transmission and scanning electron microscopic observations of
      the nanocomposites also showed that fracture surface became rougher by increasing
      the content of filler loading from 1 to 4% wt.

PMID- 24688422
TI  - Dynamics of a diffusive predator-prey model with general nonlinear functional
      response.
AB  - We study a diffusive predator-prey model with nonconstant death rate and general
      nonlinear functional response. Firstly, stability analysis of the equilibrium for
      reduced ODE system is discussed. Secondly, sufficient and necessary conditions
      which guarantee the predator and the prey species to be permanent are obtained.
      Furthermore, sufficient conditions for the global asymptotical stability of the
      unique positive equilibrium of the system are derived by using the method of
      Lyapunov function. Finally, we show that there are no nontrivial steady state
      solutions for certain parameter configuration. 

PMID- 24688423
TI  - Performance of different herbicides in dry-seeded rice in Bangladesh.
AB  - A field study was conducted in the boro season of 2011-12 and aman season of 2012
      at Jessore, Bangladesh, to evaluate the performance of sequential applications of
      preemergence herbicides (oxadiargyl 80 g ai ha(-1), pendimethalin 850 g ai ha(
      1), acetachlor + bensulfuranmethyl 240 g ai ha(-1), and pyrazosulfuron 15 g ai
      ha(-1)) followed by a postemergence herbicide (ethoxysulfuron 18 g ai ha(-1)) in
      dry-seeded rice. All evaluated herbicides reduced weed density and biomass by a
      significant amount. Among herbicides, pendimethalin, oxadiargyl, and acetachlor +
      bensulfuranmethyl performed very well against grasses; pyrazosulfuron, on the
      other hand, was not effective. The best herbicide for broadleaf weed control was
      oxadiargyl (65-85% control); pendimethalin and acetachlor + bensulfuraonmethyl
      were not effective for this purpose. The best combination for weed control was
      oxadiargyl followed by ethoxysulfuron in the boro season and oxadiargyl followed
      by a one-time hand weeding in the aman season. Compared with the partial weedy
      plots (hand weeded once), oxadiargyl followed by ethoxysulfuron (4.13 t ha(-1))
      provided a 62% higher yield in the boro season while oxadiargyl followed by a one
      time hand weeding (4.08 t ha(-1)) provided a 37% higher yield in the aman season.

PMID- 24688424
TI  - Effect of elevated CO2, O3, and UV radiation on soils.
AB  - In this work, we have attempted to review the current knowledge on the impact of
      elevated CO2, O3, and UV on soils. Elevated CO2 increases labile and stabile soil
      C pool as well as efficiency of organic pollutants rhizoremediation and
      phytoextraction of heavy metals. Conversely, both elevated O3 and UV radiation
      decrease inputs of assimilates to the rhizosphere being accompanied by inhibitory
      effects on decomposition processes, rhizoremediation, and heavy metals
      phytoextraction efficiency. Contrary to elevated CO2, O3, or UV-B decreases soil
      microbial biomass, metabolisable C, and soil N t content leading to higher C/N of
      soil organic matter. Elevated UV-B radiation shifts soil microbial community and
      decreases populations of soil meso- and macrofauna via direct effect rather than
      by induced changes of litter quality and root exudation as in case of elevated
      CO2 or O3. CO2 enrichment or increased UV-B is hypothesised to stimulate or
      inhibit both plant and microbial competitiveness for soluble soil N,
      respectively, whereas O3 favours only microbial competitive efficiency.
      Understanding the consequences of elevated CO2, O3, and UV radiation for soils,
      especially those related to fertility, phytotoxins inputs, elements cycling,
      plant-microbe interactions, and decontamination of polluted sites, presents a
      knowledge gap for future research. 

PMID- 24688425
TI  - Medical students' experience of and reaction to stress: the role of depression
      and anxiety.
AB  - BACKGROUND: Medical school is recognized as a stressful environment that often
      has a negative effect on students' academic performance, physical health, and
      psychosocial well-being. Previous studies have not identified differences between
      depressed and nondepressed and anxious and nonanxious medical students'
      experiences of stress or their reactions to stressors. The present study aimed to
      identify the prevalence of depression and anxiety among a sample of 358 medical
      students attending a private university in Malaysia and to examine differences
      according to participants' gender, year of study, and stage of training
      (preclinical and clinical). Additionally, this study examined the extent to which
      stress predicts depression and anxiety, differences between depressed and
      nondepressed medical students' experiences of and reactions to stressors, and
      differences between anxious and nonanxious medical students' experiences of and
      reactions to stressors. METHODS: The Student Life Stress Inventory was used to
      measure stress and reaction to stressors and the Depression, Anxiety, and Stress
      Scale was used to measure depression and anxiety. RESULTS: The results showed
      that 44% (n = 158) of the students were anxious and 34.9% (n = 125) were
      depressed. More female students exhibited anxiety compared to male students.
      Stress is a predictor for depression and anxiety. A significant difference was
      found between depressed and nondepressed and anxious and nonanxious students'
      experience of stressors due to frustration, change, and their emotional reaction
      to stressors. CONCLUSION: Overall, depressed and anxious students were found to
      experience more stress and react differently to stressors compared to
      nondepressed and nonanxious students.

PMID- 24688426
TI  - New improved fractional order differentiator models based on optimized digital
      differentiators.
AB  - Different evolutionary algorithms (EAs), namely, particle swarm optimization
      (PSO), genetic algorithm (GA), and PSO-GA hybrid optimization, have been used to
      optimize digital differential operators so that these can be better fitted to
      exemplify their new improved fractional order differentiator counterparts. First,
      the paper aims to provide efficient 2nd and 3rd order operators in connection
      with process of minimization of error fitness function by registering mean,
      median, and standard deviation values in different random iterations to ascertain
      the best results among them, using all the abovementioned EAs. Later, these
      optimized operators are discretized for half differentiator models for utilizing
      their restored qualities inhibited from their optimization. Simulation results
      present the comparisons of the proposed half differentiators with the existing
      and amongst different models based on 2nd and 3rd order optimized operators.
      Proposed half differentiators have been observed to approximate the ideal half
      differentiator and also outperform the existing ones reasonably well in complete
      range of Nyquist frequency. 

PMID- 24688427
TI  - Chain graph models to elicit the structure of a Bayesian network.
AB  - Bayesian networks are possibly the most successful graphical models to build
      decision support systems. Building the structure of large networks is still a
      challenging task, but Bayesian methods are particularly suited to exploit
      experts' degree of belief in a quantitative way while learning the network
      structure from data. In this paper details are provided about how to build a
      prior distribution on the space of network structures by eliciting a chain graph
      model on structural reference features. Several structural features expected to
      be often useful during the elicitation are described. The statistical background
      needed to effectively use this approach is summarized, and some potential
      pitfalls are illustrated. Finally, a few seminal contributions from the
      literature are reformulated in terms of structural features. 

PMID- 24688428
TI  - Fuzzy filtering method for color videos corrupted by additive noise.
AB  - A novel method for the denoising of color videos corrupted by additive noise is
      presented in this paper. The proposed technique consists of three principal
      filtering steps: spatial, spatiotemporal, and spatial postprocessing. In contrast
      to other state-of-the-art algorithms, during the first spatial step, the eight
      gradient values in different directions for pixels located in the vicinity of a
      central pixel as well as the R, G, and B channel correlation between the
      analogous pixels in different color bands are taken into account. These gradient
      values give the information about the level of contamination then the designed
      fuzzy rules are used to preserve the image features (textures, edges, sharpness,
      chromatic properties, etc.). In the second step, two neighboring video frames are
      processed together. Possible local motions between neighboring frames are
      estimated using block matching procedure in eight directions to perform
      interframe filtering. In the final step, the edges and smoothed regions in a
      current frame are distinguished for final postprocessing filtering. Numerous
      simulation results confirm that this novel 3D fuzzy method performs better than
      other state-of-the-art techniques in terms of objective criteria (PSNR, MAE, NCD,
      and SSIM) as well as subjective perception via the human vision system in the
      different color videos. 

PMID- 24688429
TI  - Reliability prediction of ontology-based service compositions using Petri net and
      time series models.
AB  - OWL-S, one of the most important Semantic Web service ontologies proposed to
      date, provides a core ontological framework and guidelines for describing the
      properties and capabilities of their web services in an unambiguous, computer
      interpretable form. Predicting the reliability of composite service processes
      specified in OWL-S allows service users to decide whether the process meets the
      quantitative quality requirement. In this study, we consider the runtime quality
      of services to be fluctuating and introduce a dynamic framework to predict the
      runtime reliability of services specified in OWL-S, employing the Non-Markovian
      stochastic Petri net (NMSPN) and the time series model. The framework includes
      the following steps: obtaining the historical response times series of individual
      service components; fitting these series with a autoregressive-moving-average
      model (ARMA for short) and predicting the future firing rates of service
      components; mapping the OWL-S process into a NMSPN model; employing the predicted
      firing rates as the model input of NMSPN and calculating the normal completion
      probability as the reliability estimate. In the case study, a comparison between
      the static model and our approach based on experimental data is presented and it
      is shown that our approach achieves higher prediction accuracy. 

PMID- 24688430
TI  - Analysis of change in the wind speed ratio according to apartment layout and
      solutions.
AB  - Apartment complexes in various forms are built in downtown areas. The arrangement
      of an apartment complex has great influence on the wind flow inside it. There are
      issues of residents' walking due to gust occurrence within apartment complexes,
      problems with pollutant emission due to airflow congestion, and heat island and
      cool island phenomena in apartment complexes. Currently, the forms of internal
      arrangements of apartment complexes are divided into the flat type and the tower
      type. In the present study, a wind tunnel experiment and computational fluid
      dynamics (CFD) simulation were performed with respect to internal wind flows in
      different apartment arrangement forms. Findings of the wind tunnel experiment
      showed that the internal form and arrangement of an apartment complex had
      significant influence on its internal airflow. The wind velocity of the buildings
      increased by 80% at maximum due to the proximity effects between the buildings.
      The CFD simulation for relaxing such wind flows indicated that the wind velocity
      reduced by 40% or more at maximum when the paths between the lateral sides of the
      buildings were extended. 

PMID- 24688431
TI  - Evaluation of antidiabetic and antioxidant properties of Brucea javanica seed.
AB  - The ethanol extract of B. javanica seed was fractionated with solvents of
      different polarities and tested for antioxidant activities by several assays
      including DPPH radical scavenging activity, ferric reducing antioxidant power
      (FRAP), ferrous ion chelating activity (FCA), and nitric oxide radical scavenging
      activity (NORSA) along with their polyphenolic contents. Antidiabetic activity
      was evaluated both in vitro and in vivo using a glycogen phosphorylase alpha
      (GPalpha) inhibition assay and oral glucose tolerance test (OGTT) in nondiabetic
      rats. The ethyl acetate fraction (EAF), rich in tannin, exhibited the strongest
      antioxidant activities to DPPH, FRAP, and NORSA, except for FCA. The EAF also
      exerted a dose-depended inhibition of GPalpha (IC50 = 0.75 mg/ml). Further
      evaluation of hypoglycemic effect on OGGT indicated that rats treated with EAF
      (125 mg/kg bw) showed a 39.91% decrease (P < 0.05) in blood glucose levels at 30
      min, and continuous fall (P < 0.05) of 28.89% and 20.29% was observed in the
      following hours (60 and 90 min) compared to the normal control during OGTT. The
      EAF was applied to polyamide column chromatography, and the resulting tannin-free
      fraction was tested for both GPalpha inhibition and antioxidant (DPPH only)
      activity. The GP alpha inhibitory activity was retained, while antioxidant
      activity was lost (4.6-fold) after tannin removal. These results concluded that
      the GPalpha inhibitory activity initially detected was primarily due to the
      compounds other than tannins, whereas antioxidant activity was mainly due to the
      tannins.

PMID- 24688432
TI  - Next generation sequencing: potential and application in drug discovery.
AB  - The world has now entered into a new era of genomics because of the continued
      advancements in the next generation high throughput sequencing technologies,
      which includes sequencing by synthesis-fluorescent in situ sequencing (FISSEQ),
      pyrosequencing, sequencing by ligation using polony amplification, supported
      oligonucleotide detection (SOLiD), sequencing by hybridization along with
      sequencing by ligation, and nanopore technology. Great impacts of these methods
      can be seen for solving the genome related problems of plant and animal kingdom
      that will open the door of a new era of genomics. This may ultimately overcome
      the Sanger sequencing that ruled for 30 years. NGS is expected to advance and
      make the drug discovery process more rapid. 

PMID- 24688434
TI  - A security-awareness virtual machine management scheme based on Chinese wall
      policy in cloud computing.
AB  - Cloud computing gets increasing attention for its capacity to leverage developers
      from infrastructure management tasks. However, recent works reveal that side
      channel attacks can lead to privacy leakage in the cloud. Enhancing isolation
      between users is an effective solution to eliminate the attack. In this paper, to
      eliminate side channel attacks, we investigate the isolation enhancement scheme
      from the aspect of virtual machine (VM) management. The security-awareness VMs
      management scheme (SVMS), a VMs isolation enhancement scheme to defend against
      side channel attacks, is proposed. First, we use the aggressive conflict of
      interest relation (ACIR) and aggressive in ally with relation (AIAR) to describe
      user constraint relations. Second, based on the Chinese wall policy, we put
      forward four isolation rules. Third, the VMs placement and migration algorithms
      are designed to enforce VMs isolation between the conflict users. Finally, based
      on the normal distribution, we conduct a series of experiments to evaluate SVMS.
      The experimental results show that SVMS is efficient in guaranteeing isolation
      between VMs owned by conflict users, while the resource utilization rate
      decreases but not by much. 

PMID- 24688433
TI  - The influence of pH and temperature on the stability of N
      [(piperidine)methylene]daunorubicin Hydrochloride and a comparison of the
      stability of daunorubicin and its four new amidine derivatives in aqueous
      solutions.
AB  - The influence of pH and temperature on the stability of N
      [(piperidine)methylene]daunorubicin hydrochloride (PPD) was investigated.
      Degradation was studied using an HPLC method. Specific acid-base catalysis of PPD
      involves hydrolysis of protonated molecules of PPD catalyzed by hydrogen ions and
      spontaneous hydrolysis under the influence of water zwitterions, unprotonated
      molecules, and monoanions of PPD. The thermodynamic parameters of these
      reactions, energy, enthalpy, and entropy, were calculated. Also, the stability of
      daunorubicin and its new amidine derivatives (piperidine, morpholine,
      pyrrolidine, and hexahydroazepin-1-yl) in aqueous solutions was compared and
      discussed. 

PMID- 24688435
TI  - Manufacturing and shear response characterization of carbon nanofiber modified
      CFRP using the out-of-autoclave-vacuum-bag-only cure process.
AB  - The interlaminar shear response is studied for carbon nanofiber (CNF) modified
      out-of-autoclave-vacuum-bag-only (OOA-VBO) carbon fiber reinforced plastic
      (CFRP). Commercial OOA-VBO prepregs were coated with a CNF modified epoxy
      solution and a control epoxy solution without CNF to make CNF modified samples
      and control samples, respectively. Tensile testing was used to study the in-plane
      shear performance of [+/- 45 degrees ]4s composite laminates. Significant
      difference in failure modes between the control and CNF modified CFRPs was
      identified. The control samples experienced half-plane interlaminar delamination,
      whereas the CNF modified samples experienced a localized failure in the
      intralaminar region. Digital image correlation (DIC) surface strain results of
      the control sample showed no further surface strain increase along the
      delaminated section when the sample was further elongated prior to sample
      failure. On the other hand, the DIC results of the CNF modified sample showed
      that the surface strain increased relatively and uniformly across the CFRP as the
      sample was further elongated until sample failure. The failure mode evidence
      along with microscope pictures indicated that the CNF modification acted as a
      beneficial reinforcement inhibiting interlaminar delamination.

PMID- 24688436
TI  - A new high-order stable numerical method for matrix inversion.
AB  - A stable numerical method is proposed for matrix inversion. The new method is
      accompanied by theoretical proof to illustrate twelfth-order convergence. A
      discussion of how to achieve the convergence using an appropriate initial value
      is presented. The application of the new scheme for finding Moore-Penrose inverse
      will also be pointed out analytically. The efficiency of the contributed
      iterative method is clarified on solving some numerical examples. 

PMID- 24688437
TI  - Characterization of the existence of an N0-completion of a partial N0-matrix with
      an associated directed cycle.
AB  - An n * n matrix is called an N 0-matrix if all its specified principal minors are
      nonpositive. In the context of partial matrices, a partial matrix is called a
      partial N 0-matrix if all its specified principal minors are nonpositive. In this
      paper we characterize the existence of an N 0-matrix completion of a partial N 0
      matrix whose associated graph is a directed cycle. 

PMID- 24688438
TI  - Phase transformation of VO2 nanoparticles assisted by microwave heating.
AB  - The microwave assisted synthesis nowadays attracts a great deal of attention.
      Monoclinic phase VO2 (M) was prepared from NH4VO3 and H2C2O4 . 2H2O by a rapid
      microwave assisted technique. The synthesis parameters, microwave irradiation
      time, microwave power, and calcinations temperature were systematically varied
      and their influences on the structure and morphology were evaluated. The
      microwave power level has been carried out in range 180-600 W. TEM analysis
      demonstrated nanosized samples. The structural and morphological properties were
      measured using XRD, TEM, and thermal analyses. The variations of vanadium phase
      led to thermochromic properties.

PMID- 24688439
TI  - Synthesis of Cr(III)-morin complex: characterization and antioxidant study.
AB  - The complex formation between Cr(III) and morin was carried out in methanol and
      confirmed by analytical characterization using UV-Vis, IR, (1)H NMR, and TG-DTA.
      UV-Vis shows significant bathochromic shift in benzoyl upon coordination as well
      as IR well illustrates the peak shift of C=O group and formation of a O-Cr(III)
      bond. Likewise, (1)H NMR studies clarify that Cr(III) metal ion replaces the 5OH
      proton hence; 5-hydroxy-4-keto site is employed by morin in chelation to form six
      membered stable ring system out of three available chelating sites. In addition,
      TG-DTA denotes the presence of coordinated and crystalline water molecules. The
      melting point of the complex was found to be 389  degrees C by DSC. In addition,
      Cr(III)-morin complex was found to be a more potent antioxidant than morin as
      evaluated by DPPH* and FRAP methods.

PMID- 24688440
TI  - Correction of faulty sensors in phased array radars using symmetrical sensor
      failure technique and cultural algorithm with differential evolution.
AB  - Three issues regarding sensor failure at any position in the antenna array are
      discussed. We assume that sensor position is known. The issues include raise in
      sidelobe levels, displacement of nulls from their original positions, and
      diminishing of null depth. The required null depth is achieved by making the
      weight of symmetrical complement sensor passive. A hybrid method based on memetic
      computing algorithm is proposed. The hybrid method combines the cultural
      algorithm with differential evolution (CADE) which is used for the reduction of
      sidelobe levels and placement of nulls at their original positions. Fitness
      function is used to minimize the error between the desired and estimated beam
      patterns along with null constraints. Simulation results for various scenarios
      have been given to exhibit the validity and performance of the proposed
      algorithm. 

PMID- 24688441
TI  - L-fuzzy fixed points theorems for L-fuzzy mappings via betaFL-admissible pair.
AB  - We define the concept of betaFL-admissible for a pair of L-fuzzy mappings and
      establish the existence of common L-fuzzy fixed point theorem. Our result
      generalizes some useful results in the literature. We provide an example to
      support our result.

PMID- 24688442
TI  - Effective application of improved profit-mining algorithm for the interday
      trading model.
AB  - Many real world applications of association rule mining from large databases help
      users make better decisions. However, they do not work well in financial markets
      at this time. In addition to a high profit, an investor also looks for a low risk
      trading with a better rate of winning. The traditional approach of using minimum
      confidence and support thresholds needs to be changed. Based on an interday model
      of trading, we proposed effective profit-mining algorithms which provide
      investors with profit rules including information about profit, risk, and winning
      rate. Since profit-mining in the financial market is still in its infant stage,
      it is important to detail the inner working of mining algorithms and illustrate
      the best way to apply them. In this paper we go into details of our improved
      profit-mining algorithm and showcase effective applications with experiments
      using real world trading data. The results show that our approach is practical
      and effective with good performance for various datasets. 

PMID- 24688443
TI  - Mechanical characteristics of hardened concrete with different mineral
      admixtures: a review.
AB  - The available literature identifies that the addition of mineral admixture as
      partial replacement of cement improves the microstructure of the concrete (i.e.,
      porosity and pore size distribution) as well as increasing the mechanical
      characteristics such as drying shrinkage and creep, compressive strength, tensile
      strength, flexural strength, and modulus of elasticity; however, no single
      document is available in which review and comparison of the influence of the
      addition of these mineral admixtures on the mechanical characteristics of the
      hardened pozzolanic concretes are presented. In this paper, based on the reported
      results in the literature, mechanical characteristics of hardened concrete
      partially containing mineral admixtures including fly ash (FA), silica fume (SF),
      ground granulated blast furnace slag (GGBS), metakaolin (MK), and rice husk ash
      (RHA) are discussed and it is concluded that the content and particle size of
      mineral admixture are the parameters which significantly influence the mechanical
      properties of concrete. All mineral admixtures enhance the mechanical properties
      of concrete except FA and GGBS which do not show a significant effect on the
      strength of concrete at 28 days; however, gain in strength at later ages is
      considerable. Moreover, the comparison of the mechanical characteristics of
      different pozzolanic concretes suggests that RHA and SF are competitive. 

PMID- 24688445
TI  - Automatic recognition of seismic intensity based on RS and GIS: a case study in
      Wenchuan Ms8.0 earthquake of China.
AB  - In recent years, earthquakes have frequently occurred all over the world, which
      caused huge casualties and economic losses. It is very necessary and urgent to
      obtain the seismic intensity map timely so as to master the distribution of the
      disaster and provide supports for quick earthquake relief. Compared with
      traditional methods of drawing seismic intensity map, which require many
      investigations in the field of earthquake area or are too dependent on the
      empirical formulas, spatial information technologies such as Remote Sensing (RS)
      and Geographical Information System (GIS) can provide fast and economical way to
      automatically recognize the seismic intensity. With the integrated application of
      RS and GIS, this paper proposes a RS/GIS-based approach for automatic recognition
      of seismic intensity, in which RS is used to retrieve and extract the information
      on damages caused by earthquake, and GIS is applied to manage and display the
      data of seismic intensity. The case study in Wenchuan Ms8.0 earthquake in China
      shows that the information on seismic intensity can be automatically extracted
      from remotely sensed images as quickly as possible after earthquake occurrence,
      and the Digital Intensity Model (DIM) can be used to visually query and display
      the distribution of seismic intensity. 

PMID- 24688444
TI  - Aquaporin-1 expression in proliferative vitreoretinopathy and in epiretinal
      membranes.
AB  - PURPOSE: Aquaporin-1 (AQP1) is involved in cell migration and proliferation;
      therefore, the purpose of the study was to investigate its expression in
      proliferative vitreoretinopathy (PVR) and epiretinal membranes (ERM). METHODS: 19
      membranes from PVR and ERM were collected following eye surgery. AQP1 mRNA and
      protein expressions were determined by RT-qPCR and immunofluorescence in the
      membranes from PVR and ERM. RESULTS: AQP1 mRNA and protein were expressed in both
      PVR and ERM as shown by RT-qPCR and immunofluorescence. AQP1 protein expression
      was heterogeneous among and between PVR and ERM and colocalized with alpha-smooth
      muscle actin ( alpha SMA) and with glial fibrillary acidic protein (GFAP). There
      were a higher percentage of cells coexpressing AQP1 and alpha SMA than AQP1 and
      GFAP. GFAP and alpha SMA did not colocalize. CONCLUSION: Our data show for the
      first time AQP1 expression in both PVR and ERM. AQP1 is expressed mostly by the
      alpha SMA-positive cells, presumably myofibroblasts, but also by GFAP-positive
      cells, assumed to be glial cells. These original findings warrant further
      functional investigations aiming at studying the potential role of AQP1 in cell
      migration and proliferation occurring during the development of PVR and ERM.

PMID- 24688446
TI  - Effect of the independent acid base variables on anion gap variation in cardiac
      surgical patients: a Stewart-Figge approach.
AB  - PURPOSE: To determine the effect of each of independent acid base variables on
      the anion gap (AG) value in cardiac surgical patients. METHODS: This
      retrospective study involved 128 cardiac surgical patients admitted for
      postoperative care. The variation of AG (AGvar) between the day of admission and
      the first postoperative day was correlated via a multiple linear regression model
      with the respective variations of the independent acid base variables, that is,
      apparent strong ion difference (SIDa), strong ion gap (SIG), carbon dioxide
      (PCO2), and albumin and phosphate concentrations. RESULTS: The variations of all
      the above variables contributed significantly to the prediction of AGvar
      (adjusted R (2) = 0.9999, F = 201890.24, and P < 0.001). According to the
      standardized coefficients (beta),  SIGvar (beta = 0.948, P < 0.001), [Albumin]var
      (beta = 0.260, P < 0.001), and [Phosphate]var (beta = 0.191, P < 0.001) were the
      major determinants of AGvar with lesser contributions from SIDa, var (beta =
      0.071, P < 0.001) and PCO2, var (beta = -0.067, P < 0.001). CONCLUSIONS: All the
      independent acid base variables contribute to the prediction of the AG value.
      However, albumin and phosphate and SIG variations seem to be the most important
      predictors, while AG appears to be rather stable with changes in PCO2 and SIDa.

PMID- 24688447
TI  - The role of cyclooxygenase in multiplication and reactivation of HSV-1 in
      vestibular ganglion neurons.
AB  - Reactivation of latent herpes simplex type 1 (HSV-1) and nerve inflammation have
      been shown to be involved in vertigo-related vestibular pathogenesis. Treatments
      of such diseases have been less than perfect. Nonsteroidal anti-inflammatory
      drugs (NSAIDs) have been reported to suppress reactivation of HSV-1 in trigeminal
      ganglions. However, whether this drug can affect reactivation of HSV-1 in
      vestibular ganglions is unclear. Due to the difficulties of constructing in vivo
      animal models, in this study, we developed a vestibular ganglion culture system,
      in which vestibular neurons were latently or lytically infected with HSV-1.
      Indomethacin and celecoxib were selected to measure their effects on HSV-1.
      Trichostatin A was used to reactivate HSV-1 in latently infected neurons.
      Cycloxygenase-2, which is the target of NSAIDs, was induced by HSV-1 in the
      lytically infected cultures, with an increase of 14-fold. Although it appeared
      that indomethacin and celecoxib showed limited but concentration-dependent
      inhibition effects on viral production under our condition, indomethacin
      decreased reactivation rate of HSV-1 by about 20%. Though more in vitro or in
      vivo studies are needed to confirm the effects of the drugs, our study may
      provide a potential way to investigate the mechanism of HSV-related vestibular
      pathogenesis as well as new treatments of vertigo-related diseases. 

PMID- 24688448
TI  - Review on cold-formed steel connections.
AB  - The concept of cold-formed light steel framing construction has been widespread
      after understanding its structural characteristics with massive research works
      over the years. Connection serves as one of the important elements for light
      steel framing in order to achieve its structural stability. Compared to hot
      rolled steel sections, cold-formed steel connections perform dissimilarity due to
      the thin-walled behaviour. This paper aims to review current researches on cold
      formed steel connections, particularly for screw connections, storage rack
      connections, welded connections, and bolted connections. The performance of these
      connections in the design of cold-formed steel structures is discussed. 

PMID- 24688449
TI  - An improved feature selection based on effective range for classification.
AB  - Feature selection is a key issue in the domain of machine learning and related
      fields. The results of feature selection can directly affect the classifier's
      classification accuracy and generalization performance. Recently, a statistical
      feature selection method named effective range based gene selection (ERGS) is
      proposed. However, ERGS only considers the overlapping area (OA) among effective
      ranges of each class for every feature; it fails to handle the problem of the
      inclusion relation of effective ranges. In order to overcome this limitation, a
      novel efficient statistical feature selection approach called improved feature
      selection based on effective range (IFSER) is proposed in this paper. In IFSER,
      an including area (IA) is introduced to characterize the inclusion relation of
      effective ranges. Moreover, the samples' proportion for each feature of every
      class in both OA and IA is also taken into consideration. Therefore, IFSER
      outperforms the original ERGS and some other state-of-the-art algorithms.
      Experiments on several well-known databases are performed to demonstrate the
      effectiveness of the proposed method. 

PMID- 24688451
TI  - Dynamic scene stitching driven by visual cognition model.
AB  - Dynamic scene stitching still has a great challenge in maintaining the global key
      information without missing or deforming if multiple motion interferences exist
      in the image acquisition system. Object clips, motion blurs, or other synthetic
      defects easily occur in the final stitching image. In our research work, we
      proceed from human visual cognitive mechanism and construct a hybrid-saliency
      based cognitive model to automatically guide the video volume stitching. The
      model consists of three elements of different visual stimuli, that is, intensity,
      edge contour, and scene depth saliencies. Combined with the manifold-based
      mosaicing framework, dynamic scene stitching is formulated as a cut path
      optimization problem in a constructed space-time graph. The cutting energy
      function for column width selections is defined according to the proposed visual
      cognition model. The optimum cut path can minimize the cognitive saliency
      difference throughout the whole video volume. The experimental results show that
      it can effectively avoid synthetic defects caused by different motion
      interferences and summarize the key contents of the scene without loss. The
      proposed method gives full play to the role of human visual cognitive mechanism
      for the stitching. It is of high practical value to environmental surveillance
      and other applications. 

PMID- 24688452
TI  - Local analysis of human cortex in MRI brain volume.
AB  - This paper describes a method for subcortical identification and labeling of 3D
      medical MRI images. Indeed, the ability to identify similarities between the most
      characteristic subcortical structures such as sulci and gyri is helpful for human
      brain mapping studies in general and medical diagnosis in particular. However,
      these structures vary greatly from one individual to another because they have
      different geometric properties. For this purpose, we have developed an efficient
      tool that allows a user to start with brain imaging, to segment the border
      gray/white matter, to simplify the obtained cortex surface, and to describe this
      shape locally in order to identify homogeneous features. In this paper, a
      segmentation procedure using geometric curvature properties that provide an
      efficient discrimination for local shape is implemented on the brain cortical
      surface. Experimental results demonstrate the effectiveness and the validity of
      our approach. 

PMID- 24688450
TI  - Application of liposomes in treatment of rheumatoid arthritis: quo vadis.
AB  - The most common treatments for rheumatoid arthritis include nonsteroidal anti
      inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic
      drugs (DMARDs), and some biological agents. However, none of the treatments
      available is able to achieve the ultimate goal of treatment, that is, drug-free
      remission. This limitation has shifted the focus of treatment to delivery
      strategies with an ability to deliver the drugs into the synovial cavity in the
      proper dosage while mitigating side effects to other tissues. A number of
      approaches like microemulsions, microspheres, liposomes, microballoons,
      cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used
      for intrasynovial delivery of these drugs. Amongst these, liposomes have proven
      to be very effective for retaining the drug in the synovial cavity by virtue of
      their size and chemical composition. The fast clearance of intra-synovially
      administered drugs can be overcome by use of liposomes leading to increased
      uptake of drugs by the target synovial cells, which in turn reduces the exposure
      of nontarget sites and eliminates most of the undesirable effects associated with
      therapy. This review focuses on the use of liposomes in treatment of rheumatoid
      arthritis and summarizes data relating to the liposome formulations of various
      drugs. It also discusses emerging trends of this promising technology. 

PMID- 24688453
TI  - SNP_NLMM: A SAS Macro to Implement a Flexible Random Effects Density for
      Generalized Linear and Nonlinear Mixed Models.
AB  - Generalized linear and nonlinear mixed models (GMMMs and NLMMs) are commonly used
      to represent non-Gaussian or nonlinear longitudinal or clustered data. A common
      assumption is that the random effects are Gaussian. However, this assumption may
      be unrealistic in some applications, and misspecification of the random effects
      density may lead to maximum likelihood parameter estimators that are
      inconsistent, biased, and inefficient. Because testing if the random effects are
      Gaussian is difficult, previous research has recommended using a flexible random
      effects density. However, computational limitations have precluded widespread use
      of flexible random effects densities for GLMMs and NLMMs. We develop a SAS macro,
      SNP_NLMM, that overcomes the computational challenges to fit GLMMs and NLMMs
      where the random effects are assumed to follow a smooth density that can be
      represented by the seminonparametric formulation proposed by Gallant and Nychka
      (1987). The macro is flexible enough to allow for any density of the response
      conditional on the random effects and any nonlinear mean trajectory. We
      demonstrate the SNP_NLMM macro on a GLMM of the disease progression of toenail
      infection and on a NLMM of intravenous drug concentration over time.

PMID- 24688454
TI  - Transition Metal(II) Complexes with Cefotaxime-Derived Schiff Base: Synthesis,
      Characterization, and Antimicrobial Studies.
AB  - New [ML2(H2O)2] complexes, where M = Co(II), Ni(II), Cu(II), and Zn(II) while L
      corresponds to the Schiff base ligand, were synthesized by condensation of
      cefotaxime with salicylaldehyde in situ in the presence of divalent metal salts
      in ethanolic medium. The complexes were characterized by elemental analyses,
      conductance, and magnetic measurements, as well as by IR and UV-Vis spectroscopy.
      The low values of the molar conductance indicate nonelectrolyte type of
      complexes. Based on spectral data and magnetic moments, an octahedral geometry
      may be proposed for Co(II), Ni(II), and Zn(II) complexes while a tetragonal
      geometry for Cu(II) complex. Molecular structure of the Schiff base ligand and
      its complexes were studied using programs dedicated to chemical modeling and
      quantomolecular calculation of chemical properties. All the synthesized complexes
      were tested for in vitro antibacterial activity against some pathogenic bacterial
      strains, namely Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa,
      Bacillus subtilis, and Staphylococcus aureus. The MIC values shown by the
      complexes against these bacterial strains revealed that the metal complexes
      possess superior antibacterial activity than the Schiff base. 

PMID- 24688455
TI  - Inflammatory cytokines presented from polymer matrices differentially generate
      and activate DCs in situ.
AB  - During infection, inflammatory cytokines mobilize and activate dendritic cells
      (DCs), which are essential for efficacious T cell priming and immune responses
      that clear the infection. Here we designed macroporous poly(lactide-co-glycolide)
      (PLG) matrices to release the inflammatory cytokines GM-CSF, Flt3L and CCL20, in
      order to mimic infection-induced DC recruitment. We then tested the ability of
      these infection mimics to function as cancer vaccines via induction of specific,
      anti-tumor T cell responses. All vaccine systems tested were able to confer
      specific anti-tumor T cell responses and longterm survival in a therapeutic, B16
      F10 melanoma model. However, GM-CSF and Flt3L vaccines resulted in similar
      survival rates, and outperformed CCL20 loaded scaffolds, even though they had
      differential effects on DC recruitment and generation. GM-CSF signaling was
      identified as the most potent chemotactic factor for conventional DCs and
      significantly enhanced surface expression of MHC(II) and CD86(+), which are
      utilized for priming T cell immunity. In contrast, Flt3L vaccines led to greater
      numbers of plasmacytoid DCs (pDCs), correlating with increased levels of T cell
      priming cytokines that amplify T cell responses. These results demonstrate that
      3D polymer matrices modified to present inflammatory cytokines may be utilized to
      effectively mobilize and activate different DC subsets in vivo for immunotherapy.

PMID- 24688456
TI  - Applying mass spectrometry-based qualitative proteomics to human amygdaloid
      complex.
AB  - The amygdaloid complex is a key brain structure involved in the expression of
      behaviors and emotions such as learning, fear, and anxiety. Brain diseases
      including depression, epilepsy, autism, schizophrenia, and Alzheimer's disease,
      have been associated with amygdala dysfunction. For several decades,
      neuroanatomical, neurophysiological, volumetric, and cognitive approaches have
      been the gold standard techniques employed to characterize the amygdala
      functionality. However, little attention has been focused specifically on the
      molecular composition of the human amygdala from the perspective of proteomics.
      We have performed a global proteome analysis employing protein and peptide
      fractionation methods followed by nano-liquid chromatography tandem mass
      spectrometry (nanoLC-MS/MS), detecting expression of at least 1820 protein
      species in human amygdala, corresponding to 1814 proteins which represent a nine
      fold increase in proteome coverage with respect to previous proteomic profiling
      of the rat amygdala. Gene ontology analysis were used to determine biological
      process represented in human amygdala highlighting molecule transport, nucleotide
      binding, and oxidoreductase and GTPase activities. Bioinformatic analyses have
      revealed that nearly 4% of identified proteins have been previously associated to
      neurodegenerative syndromes, and 26% of amygdaloid proteins were also found to be
      present in cerebrospinal fluid (CSF). In particular, a subset of amygdaloid
      proteins was mainly involved in axon guidance, synaptic vesicle release, L1CAM
      interactome, and signaling pathways transduced by NGF and NCAM1. Taken together,
      our data contributes to the repertoire of the human brain proteome, serving as a
      reference library to provide basic information for understanding the neurobiology
      of the human amygdala. 

PMID- 24688457
TI  - Attractor dynamics in local neuronal networks.
AB  - Patterns of synaptic connectivity in various regions of the brain are
      characterized by the presence of synaptic motifs, defined as unidirectional and
      bidirectional synaptic contacts that follow a particular configuration and link
      together small groups of neurons. Recent computational work proposes that a relay
      network (two populations communicating via a third, relay population of neurons)
      can generate precise patterns of neural synchronization. Here, we employ two
      distinct models of neuronal dynamics and show that simulated neural circuits
      designed in this way are caught in a global attractor of activity that prevents
      neurons from modulating their response on the basis of incoming stimuli. To
      circumvent the emergence of a fixed global attractor, we propose a mechanism of
      selective gain inhibition that promotes flexible responses to external stimuli.
      We suggest that local neuronal circuits may employ this mechanism to generate
      precise patterns of neural synchronization whose transient nature delimits the
      occurrence of a brief stimulus. 

PMID- 24688458
TI  - The brain creates illusions not just for us: sharks (Chiloscyllium griseum) can
      "see the magic" as well.
AB  - Bamboo sharks (Chiloscyllium griseum) were tested for their ability to perceive
      subjective and illusionary contours as well as line length illusions. Individuals
      were first trained to differentiate between squares, triangles, and rhomboids in
      a series of two alternative forced-choice experiments. Transfer tests then
      elucidated whether Kanizsa squares and triangles, grating gaps and phase shifted
      abutting gratings were also perceived and distinguished. The visual systems of
      most vertebrates and even invertebrates perceive illusionary contours despite the
      absence of physical luminance, color or textural differences. Sharks are no
      exception to the rule; all tasks were successfully mastered within 3-24 training
      sessions, with sharks discriminating between various sets of Kanizsa figures and
      alternative stimuli, as well as between subjective contours in >75% of all tests.
      However, in contrast to Kanizsa figures and subjective contours, sharks were not
      deceived by Muller-Lyer (ML) illusions. Here, two center lines of equal length
      are comparatively set between two arrowheads or -tails, in which case the line
      featuring the two arrow tails appears to be longer to most humans, primates and
      birds. In preparation for this experiment, lines of varying length, and lines of
      unequal length randomly featuring either two arrowheads or -tails on their ends,
      were presented first. Both sets of lines were successfully distinguished by most
      sharks. However, during presentation of the ML illusions sharks failed to succeed
      and succumbed either to side preferences or chose according to chance. 

PMID- 24688459
TI  - Ventral tegmental area activation promotes firing precision and strength through
      circuit inhibition in the primary auditory cortex.
AB  - The activation of the ventral tegmental area (VTA) can rebuild the tonotopic
      representation in the primary auditory cortex (A1), but the cellular mechanisms
      remain largely unknown. Here, we investigated the firing patterns and membrane
      potential dynamics of neurons in A1 under the influence of VTA activation using
      in vivo intracellular recording. We found that VTA activation can significantly
      reduce the variability of sound evoked responses and promote the firing precision
      and strength of A1 neurons. Furthermore, the compressed response window was
      caused by an early hyperpolarization as a result of enhanced circuit inhibition.
      Our study suggested a possible mechanism of how the reward system affects
      information processing in sensory cortex: VTA activation strengthens cortical
      inhibition, which shortens the response window of post-synaptic cortical neurons
      and further promotes the precision and strength of neuronal activity. 

PMID- 24688460
TI  - Lack of motor prediction, rather than perceptual conflict, evokes an odd
      sensation upon stepping onto a stopped escalator.
AB  - When stepping onto a stopped escalator, we often perceive an "odd sensation" that
      is never felt when stepping onto stairs. The sight of an escalator provides a
      strong contextual cue that, in expectation of the backward acceleration when
      stepping on, triggers an anticipatory forward postural adjustment driven by a
      habitual and implicit motor process. Here we contrast two theories about why this
      postural change leads to an odd sensation. The first theory links the odd
      sensation to a lack of sensorimotor prediction from all low-level implicit motor
      processes. The second theory links the odd sensation to the high-level conflict
      between the conscious awareness that the escalator is stopped and the implicit
      perception that evokes an endogenous motor program specific to a moving
      escalator. We show very similar postural changes can also arise from reflexive
      responses to visual stimuli, such as contracting/expanding optic flow fields, and
      that these reflexive responses produce similar odd sensations to the stopped
      escalator. We conclude that the high-level conflict is not necessary for such
      sensations. In contrast, the implicitly driven behavioral change itself
      essentially leads to the odd sensation in motor perception since the
      unintentional change may be less attributable to self-generated action because of
      a lack of motor predictions. 

PMID- 24688461
TI  - Lesions of the posterior paraventricular nucleus of the thalamus attenuate fear
      expression.
AB  - The paraventricular nucleus of the thalamus (PVT) has generated interest because
      of its strong projections to areas of the brain associated with the regulation of
      emotional behaviors. The posterior aspect of the PVT (pPVT) is notable for its
      projection to the central nucleus of the amygdala which is essential for the
      expression of a conditioned fear response. The present study was done to
      determine if the pPVT is involved in the expression of fear by examining the
      effect of post-conditioning lesions of the pPVT. Male rats were trained to bar
      press for food pellets on a variable ratio schedule. Fear conditioning was done
      using auditory tones (30 s) that co-terminate with footschocks (0.65 mA, 1.0 s).
      Rats were anesthetized 24 h later and small bilateral electrolytic lesions of the
      pPVT were made. Fear expression to the tone was assessed using suppression of bar
      pressing and freezing after one week of recovery from the surgical procedure.
      Small bilateral lesions of the pPVT increased bar-pressing for food and decreased
      freezing during the presentation of the conditioned tone. Lesions of the pPVT had
      no effect on fear extinction, fear conditioning to a novel tone, or the
      motivation for food as assessed using a progressive ratio (PR) schedule. The
      results of the experiment support a role for the pPVT in fear expression. In
      contrast, the pPVT does not appear to be involved in fear learning or extinction
      nor does it appear to play a role in the motivation of rats to bar press for
      food. 

PMID- 24688462
TI  - The VWFA: it's not just for words anymore.
AB  - Reading is an important but phylogenetically new skill. While neuroimaging
      studies have identified brain regions used in reading, it is unclear to what
      extent these regions become specialized for use predominantly in reading vs.
      other tasks. Over the past several years, our group has published three studies
      addressing this question, particularly focusing on whether the putative visual
      word form area (VWFA) is used predominantly in reading, or whether it is used
      more generally in a number of tasks. Our three studies utilize a range of
      neuroimaging techniques, including task based fMRI experiments, a seed based
      resting state functional connectivity (RSFC) experiment, and a network based RSFC
      experiment. Overall, our studies indicate that the VWFA is not used specifically
      or even predominantly for reading. Rather the VWFA is a general use region that
      has processing properties making it particularly useful for reading, though it
      continues to be used in any task that requires its general processing properties.
      Our network based RSFC analysis extends this finding to other regions typically
      thought to be used predominantly for reading. Here, we review these findings and
      describe how the three studies complement each other. Then, we argue that
      conceptualizing the VWFA as a brain region with specific processing
      characteristics rather than a brain region devoted to a specific stimulus class,
      allows us to better explain the activity seen in this region during a variety of
      tasks. Having this type of conceptualization not only provides a better
      understanding of the VWFA but also provides a framework for understanding other
      brain regions, as it affords an explanation of function that is in keeping with
      the long history of studying the brain in terms of the type of information
      processing performed (Posner, 1978). 

PMID- 24688463
TI  - Factors associated with the modulation of pain by visual distortion of body size.
AB  - Modulation of pain using visual distortion of body size (VDBS) has been the
      subject of various reports. However, the mechanism underlying the effect of VDBS
      on pain has been less often studied. In the present study, factors associated
      with modulation of pain threshold by VDBS were investigated. Visual feedback in
      the form of a magnified image of the hand was provided to 44 healthy adults to
      examine changes in pain. In participants with a higher pain threshold when visual
      feedback of a magnified image of the hand was provided, the two-point
      discrimination threshold decreased. In contrast, participants with a lower pain
      threshold with visual feedback of a magnified image of the hand experienced
      unpleasant emotions toward the magnified image of the hand. Interestingly, this
      emotional reaction was strongly associated with negative body consciousness in
      several subjects. These data suggested an analgesic effect of visual feedback in
      the form of a magnified image of the hand is only when tactile perception is
      vivid and the emotional reaction toward the magnified image is moderate. The
      results also suggested that negative body consciousness is important for the
      modulation of pain using VDBS. 

PMID- 24688464
TI  - Differential hippocampal and retrosplenial involvement in egocentric-updating,
      rotation, and allocentric processing during online spatial encoding: an fMRI
      study.
AB  - The way new spatial information is encoded seems to be crucial in disentangling
      the role of decisive regions within the spatial memory network (i.e.,
      hippocampus, parahippocampal, parietal, retrosplenial,...). Several data sources
      converge to suggest that the hippocampus is not always involved or indeed
      necessary for allocentric processing. Hippocampal involvement in spatial coding
      could reflect the integration of new information generated by "online" self
      related changes. In this fMRI study, the participants started by encoding several
      object locations in a virtual reality environment and then performed a pointing
      task. Allocentric encoding was maximized by using a survey perspective and an
      object-to-object pointing task. Two egocentric encoding conditions were used,
      involving self-related changes processed under a first-person perspective and
      implicating a self-to-object pointing task. The Egocentric-updating condition
      involved navigation whereas the Egocentric with rotation only condition involved
      orientation changes only. Conjunction analysis of spatial encoding conditions
      revealed a wide activation of the occipito-parieto-frontal network and several
      medio-temporal structures. Interestingly, only the cuneal areas were
      significantly more recruited by the allocentric encoding in comparison to other
      spatial conditions. Moreover, the enhancement of hippocampal activation was found
      during Egocentric-updating encoding whereas the retrosplenial activation was
      observed during the Egocentric with rotation only condition. Hence, in some
      circumstances, hippocampal and retrosplenial structures-known for being involved
      in allocentric environmental coding-demonstrate preferential involvement in the
      egocentric coding of space. These results indicate that the raw differentiation
      between allocentric versus egocentric representation seems to no longer be
      sufficient in understanding the complexity of the mechanisms involved during
      spatial encoding. 

PMID- 24688465
TI  - Topological organization of the "small-world" visual attention network in
      children with attention deficit/hyperactivity disorder (ADHD).
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most commonly
      diagnosed childhood psychiatric disorder. Disrupted sustained attention is one of
      the most significant behavioral impairments in this disorder. We mapped systems
      level topological properties of the neural network responsible for sustained
      attention during a visual sustained task, on the premise that strong associations
      between anomalies in network features and clinical measures of ADHD would emerge.
      METHODS: Graph theoretic techniques (GTT) and bivariate network-based statistics
      (NBS) were applied to fMRI data from 22 children with ADHD combined-type and 22
      age-matched neurotypicals, to evaluate the topological and nodal-pairing features
      in the functional brain networks. Correlation testing for relationships between
      network properties and clinical measures were then performed. RESULTS: The visual
      attention network showed significantly reduced local-efficiency and nodal
      efficiency in frontal and occipital regions in ADHD. Measures of degree and
      between-centrality pointed to hyper-functioning in anterior cingulate cortex and
      hypo-functioning in orbito-frontal, middle-occipital, superior-temporal, supra
      central, and supra-marginal gyri in ADHD. NBS demonstrated significantly reduced
      pair-wise connectivity in an inner-network, encompassing right parietal and
      temporal lobes and left occipital lobe, in the ADHD group. CONCLUSIONS: These
      data suggest that atypical topological features of the visual attention network
      contribute to classic ADHD symptomatology, and may underlie the inattentiveness
      and hyperactivity/impulsivity that are characteristics of this syndrome.

PMID- 24688466
TI  - Human motion characteristics in relation to feeling familiar or frightened during
      an announced short interaction with a proactive humanoid.
AB  - During an unannounced encounter between two humans and a proactive humanoid (NAO,
      Aldebaran Robotics), we study the dependencies between the human partners'
      affective experience (measured via the answers to a questionnaire) particularly
      regarding feeling familiar and feeling frightened, and their arm and head motion
      [frequency and smoothness using Inertial Measurement Units (IMU)]. NAO starts and
      ends its interaction with its partners by non-verbally greeting them hello
      (bowing) and goodbye (moving its arm). The robot is invested with a real and
      useful task to perform: handing each participant an envelope containing a
      questionnaire they need to answer. NAO's behavior varies from one partner to the
      other (Smooth with X vs. Resisting with Y). The results show high positive
      correlations between feeling familiar while interacting with the robot and: the
      frequency and smoothness of the human arm movement when waving back goodbye, as
      well as the smoothness of the head during the whole encounter. Results also show
      a negative dependency between feeling frightened and the frequency of the human
      arm movement when waving back goodbye. The principal component analysis (PCA)
      suggests that, in regards to the various motion measures examined in this paper,
      the head smoothness and the goodbye gesture frequency are the most reliable
      measures when it comes to considering the familiar experienced by the
      participants. The PCA also points out the irrelevance of the goodbye motion
      frequency when investigating the participants' experience of fear in its relation
      to their motion characteristics. The results are discussed in light of the major
      findings of studies on body movements and postures accompanying specific
      emotions. 

PMID- 24688467
TI  - The BDNF effects on dendritic spines of mature hippocampal neurons depend on
      neuronal activity.
AB  - The fine tuning of neural networks during development and learning relies upon
      both functional and structural plastic processes. Changes in the number as well
      as in the size and shape of dendritic spines are associated to long-term activity
      dependent synaptic plasticity. However, the molecular mechanisms translating
      functional into structural changes are still largely unknown. In this context,
      neurotrophins, like Brain-Derived Neurotrophic Factor (BDNF), are among promising
      candidates. Specifically BDNF-TrkB receptor signaling is crucial for activity
      dependent strengthening of synapses in different brain regions. BDNF application
      has been shown to positively modulate dendritic and spine architecture in
      cortical and hippocampal neurons as well as structural plasticity in vitro.
      However, a global BDNF deprivation throughout the central nervous system (CNS)
      resulted in very mild structural alterations of dendritic spines, questioning the
      relevance of the endogenous BDNF signaling in modulating the development and the
      mature structure of neurons in vivo. Here we show that a loss-of-function
      approach, blocking BDNF results in a significant reduction in dendritic spine
      density, associated with an increase in spine length and a decrease in head
      width. These changes are associated with a decrease in F-actin levels within
      spine heads. On the other hand, a gain-of-function approach, applying exogenous
      BDNF, could not reproduce the increase in spine density or the changes in spine
      morphology previously described. Taken together, we show here that the effects
      exerted by BDNF on the dendritic architecture of hippocampal neurons are
      dependent on the neuron's maturation stage. Indeed, in mature hippocampal neurons
      in vitro as shown in vivo BDNF is specifically required for the activity
      dependent maintenance of the mature spine phenotype. 

PMID- 24688468
TI  - Motor Asymmetry Attenuation in Older Adults during Imagined Arm Movements.
AB  - Laterality is an important feature of motor behavior. Several studies have shown
      that lateralization in right-handed young adults (i.e., right versus left arm
      superiority) emerges also during imagined actions, that is when an action is
      internally simulated without any motor output. Such information, however, is
      lacking for elderly people and it could be valuable to further comprehend the
      evolution of mental states of action in normal aging. Here, we evaluated the
      influence of age on motor laterality during mental actions. Twenty-four young
      (mean age: 24.7 +/- 4.4 years) and 24 elderly (mean age: 72.4 +/- 3.6 years)
      participants mentally simulated and actually executed pointing movements with
      either their dominant-right or non-dominant-left arm in the horizontal plane. We
      recorded and analyzed the time of actual and mental movements and looked for
      differences between groups and arms. In addition, electromyographic activity from
      arm muscle was recorded to quantify any enhancement in muscle activation during
      mental actions. Our findings indicated that both groups mentally simulated arm
      movements without activating the muscles of the right or the left arm above the
      baseline level. This finding suggests that young and, notably, elderly adults are
      able to generate covert actions without any motor output. We found that manual
      asymmetries (i.e., faster movements with the right arm) were preserved in young
      adults for both actual and mental movements. In elderly adults, manual
      asymmetries were observed for actual but not for mental movements (i.e., equal
      movement times for both arms). These findings clearly indicate an age-related
      reduction of motor laterality during mental actions. 

PMID- 24688469
TI  - Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by
      voluntary physical exercise.
AB  - The senescence-accelerated SAMP8 mouse model displays features of cognitive
      decline and Alzheimer's disease. With the purpose of identifying potential
      epigenetic markers involved in aging and neurodegeneration, here we analyzed the
      expression of 84 mature miRNAs, the expression of histone-acetylation regulatory
      genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8
      mice, using SAMR1 mice as control. We also examined the modulation of these
      parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were
      differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs
      were responsive to exercise in both strains. SAMP8 mice showed alterations in
      genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and
      modulation of Hdac3 and Hdac5 gene expression by exercise. Global histone H3
      acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached
      control levels in response to exercise. In sum, data presented here provide new
      candidate epigenetic markers for aging and neurodegeneration and suggest that
      exercise training may prevent or delay some epigenetic alterations associated
      with accelerated aging. 

PMID- 24688470
TI  - Enhanced self-administration of the CB1 receptor agonist WIN55,212-2 in olfactory
      bulbectomized rats: evaluation of possible serotonergic and dopaminergic
      underlying mechanisms.
AB  - Depression has been associated with drug consumption, including heavy or
      problematic cannabis use. According to an animal model of depression and
      substance use disorder comorbidity, we combined the olfactory bulbectomy (OBX)
      model of depression with intravenous drug self-administration procedure to verify
      whether depressive-like rats displayed altered voluntary intake of the CB1
      receptor agonist WIN55,212-2 (WIN, 12.5 MUg/kg/infusion). To this aim, olfactory
      bulbectomized (OBX) and sham-operated (SHAM) Lister Hooded rats were allowed to
      self-administer WIN by lever-pressing under a continuous [fixed ratio 1 (FR-1)]
      schedule of reinforcement in 2 h daily sessions. Data showed that both OBX and
      SHAM rats developed stable WIN intake; yet, responses in OBX were constantly
      higher than in SHAM rats soon after the first week of training. In addition, OBX
      rats took significantly longer to extinguish the drug-seeking behavior after
      vehicle substitution. Acute pre-treatment with serotonin 5HT1B receptor agonist,
      CGS-12066B (2.5-10 mg/kg), did not significantly modify WIN intake in OBX and
      SHAM Lister Hooded rats. Furthermore, acute pre-treatment with CGS-12066B (10 and
      15 mg/kg) did not alter responses in parallel groups of OBX and SHAM Sprague
      Dawley rats self-administering methamphetamine under higher (FR-2) reinforcement
      schedule with nose-poking as operandum. Finally, dopamine levels in the nucleus
      accumbens (NAc) of OBX rats did not increase in response to a WIN challenge, as
      in SHAM rats, indicating a dopaminergic dysfunction in bulbectomized rats.
      Altogether, our findings suggest that a depressive-like state may alter
      cannabinoid CB1 receptor agonist-induced brain reward function and that a
      dopaminergic rather than a 5-HT1B mechanism is likely to underlie enhanced WIN
      self-administration in OBX rats. 

PMID- 24688471
TI  - Four-way regulation of mosquito yolk protein precursor genes by juvenile hormone
      , ecdysone-, nutrient-, and insulin-like peptide signaling pathways.
AB  - Anautogenous mosquito females require a meal of vertebrate blood in order to
      initiate the production of yolk protein precursors by the fat body. Yolk protein
      precursor gene expression is tightly repressed in a state-of-arrest before blood
      meal-related signals activate it and expression levels rise rapidly. The best
      understood example of yolk protein precursor gene regulation is the vitellogenin
      A gene (vg) of the yellow fever mosquito Aedes aegypti. Vg-A is regulated by (1)
      juvenile hormone signaling, (2) the ecdysone-signaling cascade, (3) the nutrient
      sensitive target-of-rapamycin signaling pathway, and (4) the insulin-like peptide
      (ILP) signaling pathway. A plethora of new studies have refined our understanding
      of the regulation of yolk protein precursor genes since the last review on this
      topic in 2005 (Attardo et al., 2005). This review summarizes the role of these
      four signaling pathways in the regulation of vg-A and focuses upon new findings
      regarding the interplay between them on an organismal level. 

PMID- 24688472
TI  - "Drug resistance associated membrane proteins".

PMID- 24688473
TI  - A critical reflection on the principles of peroxisome formation in yeast.
AB  - We have evaluated the current knowledge on peroxisome proliferation in yeast. In
      wild-type cells, peroxisomes multiply predominantly by fission at conditions that
      require peroxisome function(s) for growth. In cells that lack peroxisomes, for
      instance in pex3 and pex19 mutants or in mutants that display inheritance
      defects, peroxisomes may form de novo. We propose a novel machinery for the de
      novo formation of peroxisomes in pex3 cells, in which new peroxisomes do not
      arise from the endoplasmic reticulum. This machinery is based on the recent
      observation that membrane vesicles are present in pex3 cells that display
      peroxisomal characteristics in that they contain specific peroxisomal membrane
      and matrix proteins. These structures are the source for newly formed peroxisomes
      upon reintroduction of Pex3. Furthermore, we critically evaluate the principles
      of sorting of other peroxisomal membrane proteins to their target organelle and
      the function of the endoplasmic reticulum therein. 

PMID- 24688474
TI  - Time and causality: editorial.

PMID- 24688475
TI  - Task demands modulate decision and eye movement responses in the chimeric face
      test: examining the right hemisphere processing account.
AB  - A large and growing body of work, conducted in both brain-intact and brain
      damaged populations, has used the free viewing chimeric face test as a measure of
      hemispheric dominance for the extraction of emotional information from faces.
      These studies generally show that normal right-handed individuals tend to
      perceive chimeric faces as more emotional if the emotional expression is
      presented on the half of the face to the viewer's left ("left hemiface").
      However, the mechanisms underlying this lateralized bias remain unclear. Here, we
      examine the extent to which this bias is driven by right hemisphere processing
      advantages vs. default scanning biases in a unique way-by changing task demands.
      In particular, we compare the original task with one in which right-hemisphere
      biased processing cannot provide a decision advantage. Our behavioral and eye
      movement data are inconsistent with the predictions of a default scanning bias
      account and support the idea that the left hemiface bias found in the chimeric
      face test is largely due to strategic use of right hemisphere processing
      mechanisms. 

PMID- 24688476
TI  - Self-insight in probabilistic categorization - not implicit in children either.
AB  - The weather prediction (WP) task is a probabilistic category learning task that
      was designed to be implicit/procedural. In line with this claim, early results
      showed that patients with amnesia perform comparably to healthy participants. On
      the other hand, later research on healthy adult participants drew attention to
      the fact that the WP task is not necessarily implicit. There have been results
      showing that participants can access structural information acquired during the
      task. Participants also report that their responses are based on memories and
      rule knowledge. The contradictory results may be reconciled by assuming that
      while explicit learning occurs on the WP task in case of adults, in children the
      learning process is implicit. The present study aims at testing this hypothesis.
      Primary school children completed the WP task; the experimental group performed
      the original task, whereas in the control group cues and outcomes were associated
      on a random basis, hence their version of the WP task lacked a predictive
      structure. After each item, participants were asked whether they relied on
      guessing, intuition, "I think I know the answer" type of knowledge, memories of
      previous items, or knowledge of rules. Self-insight reports of the experimental
      group were compared to a control group. Results showed that children learn
      similarly to adults: they mostly (but not completely) rely on explicit, and not
      on implicit processes. 

PMID- 24688477
TI  - Corrigendum: Cognitive training with casual video games: points to consider.

PMID- 24688478
TI  - Interconnected growing self-organizing maps for auditory and semantic acquisition
      modeling.
AB  - Based on the incremental nature of knowledge acquisition, in this study we
      propose a growing self-organizing neural network approach for modeling the
      acquisition of auditory and semantic categories. We introduce an Interconnected
      Growing Self-Organizing Maps (I-GSOM) algorithm, which takes associations between
      auditory information and semantic information into consideration, in this paper.
      Direct phonetic-semantic association is simulated in order to model the language
      acquisition in early phases, such as the babbling and imitation stages, in which
      no phonological representations exist. Based on the I-GSOM algorithm, we
      conducted experiments using paired acoustic and semantic training data. We use a
      cyclical reinforcing and reviewing training procedure to model the teaching and
      learning process between children and their communication partners. A reinforcing
      by-link training procedure and a link-forgetting procedure are introduced to
      model the acquisition of associative relations between auditory and semantic
      information. Experimental results indicate that (1) I-GSOM has good ability to
      learn auditory and semantic categories presented within the training data; (2)
      clear auditory and semantic boundaries can be found in the network
      representation; (3) cyclical reinforcing and reviewing training leads to a
      detailed categorization as well as to a detailed clustering, while keeping the
      clusters that have already been learned and the network structure that has
      already been developed stable; and (4) reinforcing-by-link training leads to well
      perceived auditory-semantic associations. Our I-GSOM model suggests that it is
      important to associate auditory information with semantic information during
      language acquisition. Despite its high level of abstraction, our I-GSOM approach
      can be interpreted as a biologically-inspired neurocomputational model. 

PMID- 24688479
TI  - The relationship between student employability and student engagement: working
      toward a more unified theory.

PMID- 24688480
TI  - The role of executive functions in the pragmatic skills of children age 4-5.
AB  - Several studies suggest that pragmatic skills (PS) (i.e., social communication)
      deficits may be linked to executive dysfunction (i.e., cognitive processes
      required for the regulation of new and complex behaviors) in patients with
      frontal brain injuries. If impairment of executive functions (EF) causes PS
      deficits in otherwise healthy adults, could this mean that EF are necessary for
      the normal functioning of PS, even more so than cognitive maturation? If so,
      children with highly developed EF should exhibit higher levels of PS. This study
      aimed to examine the link between EF and PS among normally developing children. A
      secondary goal was to compare this relationship to that between intellectual
      quotient (IQ) and PS in order to determine which predictor explained the most
      variance. Participants were 70 French-speaking preschool children (3;10-5;7 years
      old). The PS coding system, an observational tool developed for this study, was
      used to codify the children's PS during a semi-structured conversation with a
      research assistant. Five types of EF processes were evaluated: self-control,
      inhibition, flexibility, working memory and planning. IQ was estimated by
      tallying the scores on a receptive vocabulary test and a visuoconstructive
      abilities test. The results of the test of differences between correlation
      coefficients suggest that EF contributed significantly more than IQ to the PS
      exhibited by preschoolers during conversation. More specifically, higher
      inhibition skills were correlated with a decrease in talkativeness and
      assertiveness. EF also appeared to foster quality of speech by promoting the
      ability to produce fluid utterances, free of unnecessary repetition or
      hesitation. Moreover, children with a high working memory capacity were more
      likely to formulate contingent answers and produce utterances that could be
      clearly understood by the interlocutor. Overall, these findings help us better
      understand how EF may assist children in everyday social interactions. 

PMID- 24688481
TI  - Early and late selection: effects of load, dilution and salience.

PMID- 24688482
TI  - Parkinsonian patients and poor awareness of dyskinesias.

PMID- 24688483
TI  - Defensins: antifungal lessons from eukaryotes.
AB  - Over the last years, antimicrobial peptides (AMPs) have been the focus of intense
      research toward the finding of a viable alternative to current antifungal drugs.
      Defensins are one of the major families of AMPs and the most represented among
      all eukaryotic groups, providing an important first line of host defense against
      pathogenic microorganisms. Several of these cysteine-stabilized peptides present
      a relevant effect against fungi. Defensins are the AMPs with the broader
      distribution across all eukaryotic kingdoms, namely, Fungi, Plantae, and
      Animalia, and were recently shown to have an ancestor in a bacterial organism. As
      a part of the host defense, defensins act as an important vehicle of information
      between innate and adaptive immune system and have a role in immunomodulation.
      This multidimensionality represents a powerful host shield, hard for
      microorganisms to overcome using single approach resistance strategies.
      Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major
      problem. Defensins, as other AMPs, have shown to be an effective alternative to
      the current antimycotic therapies, demonstrating potential as novel therapeutic
      agents or drug leads. In this review, we summarize the current knowledge on some
      eukaryotic defensins with antifungal action. An overview of the main targets in
      the fungal cell and the mechanism of action of these AMPs (namely, the
      selectivity for some fungal membrane components) are presented. Additionally,
      recent works on antifungal defensins structure, activity, and cytotoxicity are
      also reviewed. 

PMID- 24688485
TI  - Oct2 and Obf1 as Facilitators of B:T Cell Collaboration during a Humoral Immune
      Response.
AB  - The Oct2 protein, encoded by the Pou2f2 gene, was originally predicted to act as
      a DNA binding transcriptional activator of immunoglobulin (Ig) in B lineage
      cells. This prediction flowed from the earlier observation that an 8-bp sequence,
      the "octamer motif," was a highly conserved component of most Ig gene promoters
      and enhancers, and evidence from over-expression and reporter assays confirmed
      Oct2-mediated, octamer-dependent gene expression. Complexity was added to the
      story when Oct1, an independently encoded protein, ubiquitously expressed from
      the Pou2f1 gene, was characterized and found to bind to the octamer motif with
      almost identical specificity, and later, when the co-activator Obf1 (OCA-B,
      Bob.1), encoded by the Pou2af1 gene, was cloned. Obf1 joins Oct2 (and Oct1) on
      the DNA of a subset of octamer motifs to enhance their transactivation strength.
      While these proteins variously carried the mantle of determinants of Ig gene
      expression in B cells for many years, such a role has not been borne out for them
      by characterization of mice lacking functional copies of the genes, either as
      single or as compound mutants. Instead, we and others have shown that Oct2 and
      Obf1 are required for B cells to mature fully in vivo, for B cells to respond to
      the T cell cytokines IL5 and IL4, and for B cells to produce IL6 normally during
      a T cell dependent immune response. We show here that Oct2 affects Syk gene
      expression, thus influencing B cell receptor signaling, and that Oct2 loss blocks
      Slamf1 expression in vivo as a result of incomplete B cell maturation. Upon IL4
      signaling, Stat6 up-regulates Obf1, indirectly via Xbp1, to enable plasma cell
      differentiation. Thus, Oct2 and Obf1 enable B cells to respond normally to
      antigen receptor signals, to express surface receptors that mediate physical
      interaction with T cells, or to produce and respond to cytokines that are
      critical drivers of B cell and T cell differentiation during a humoral immune
      response. 

PMID- 24688484
TI  - The arable ecosystem as battleground for emergence of new human pathogens.
AB  - Disease incidences related to Escherichia coli and Salmonella enterica infections
      by consumption of (fresh) vegetables, sprouts, and occasionally fruits made clear
      that these pathogens are not only transmitted to humans via the "classical"
      routes of meat, eggs, and dairy products, but also can be transmitted to humans
      via plants or products derived from plants. Nowadays, it is of major concern that
      these human pathogens, especially the ones belonging to the taxonomical family of
      Enterobacteriaceae, become adapted to environmental habitats without losing their
      virulence to humans. Adaptation to the plant environment would lead to longer
      persistence in plants, increasing their chances on transmission to humans via
      consumption of plant-derived food. One of the mechanisms of adaptation to the
      plant environment in human pathogens, proposed in this paper, is horizontal
      transfer of genes from different microbial communities present in the arable
      ecosystem, like the ones originating from soil, animal digestive track systems
      (manure), water and plants themselves. Genes that would confer better adaptation
      to the phytosphere might be genes involved in plant colonization, stress
      resistance and nutrient acquisition and utilization. Because human pathogenic
      enterics often were prone to genetic exchanges via phages and conjugative
      plasmids, it was postulated that these genetic elements may be hold key
      responsible for horizontal gene transfers between human pathogens and indigenous
      microbes in agroproduction systems. In analogy to zoonosis, we coin the term
      phytonosis for a human pathogen that is transmitted via plants and not
      exclusively via animals. 

PMID- 24688486
TI  - Ring the BELL and tie the KNOX: roles for TALEs in gynoecium development.
AB  - Carpels are leaf-like structures that bear ovules, and thus play a crucial role
      in the plant life cycle. In angiosperms, carpels are the last organs produced by
      the floral meristem and they differentiate a specialized meristematic tissue from
      which ovules develop. Members of the three-amino-acid-loop-extension (TALE) class
      of homeoproteins constitute major regulators of meristematic activity. This
      family contains KNOTTED-like (KNOX) and BEL1-like (BLH or BELL) homeodomain
      proteins, which function as heterodimers. KNOX proteins can have different BELL
      partners, leading to multiple combinations with distinct activities, and thus
      regulate many aspects of plant morphogenesis, including gynoecium development.
      TALE proteins act primarily through direct regulation of hormonal pathways and
      key transcriptional regulators. This review focuses on the contribution of TALE
      proteins to gynoecium development and connects TALE transcription factors to
      carpel gene regulatory networks. 

PMID- 24688487
TI  - Lignification of developing maize (Zea mays L.) endosperm transfer cells and
      starchy endosperm cells.
AB  - Endosperm transfer cells in maize have extensive cell wall ingrowths that play a
      key role in kernel development. Although the incorporation of lignin would
      support this process, its presence in these structures has not been reported in
      previous studies. We used potassium permanganate staining combined with
      transmission electron microscopy - energy dispersive X-ray spectrometry as well
      as acriflavine staining combined with confocal laser scanning microscopy to
      determine whether the most basal endosperm transfer cells (MBETCs) contain
      lignified cell walls, using starchy endosperm cells for comparison. We
      investigated the lignin content of ultrathin sections of MBETCs treated with
      hydrogen peroxide. The lignin content of transfer and starchy cell walls was also
      determined by the acetyl bromide method. Finally, the relationship between cell
      wall lignification and MBETC growth/flange ingrowth orientation was evaluated.
      MBETC walls and ingrowths contained lignin throughout the period of cell growth
      we monitored. The same was true of the starchy cells, but those underwent an even
      more extensive growth period than the transfer cells. Both the reticulate and
      flange ingrowths were also lignified early in development. The significance of
      the lignification of maize endosperm cell walls is discussed in terms of its
      impact on cell growth and flange ingrowth orientation. 

PMID- 24688488
TI  - Microbiologically induced deterioration of concrete--a review.
AB  - Microbiologically induced deterioration (MID) causes corrosion of concrete by
      producing acids (including organic and inorganic acids) that degrade concrete
      components and thus compromise the integrity of sewer pipelines and other
      structures, creating significant problems worldwide. Understanding of the
      fundamental corrosion process and the causal agents will help us develop an
      appropriate strategy to minimize the costs in repairs. This review presents how
      microorganisms induce the deterioration of concrete, including the organisms
      involved and their colonization and succession on concrete, the microbial
      deterioration mechanism, the approaches of studying MID and safeguards against
      concrete biodeterioration. In addition, the uninvestigated research area of MID
      is also proposed. 

PMID- 24688491
TI  - Applications of recombinant Pichia pastoris in the healthcare industry.
AB  - Since the 1970s, the establishment and development of the biotech industry has
      improved exponentially, allowing the commercial production of biopharmaceutical
      proteins. Nowadays, new recombinant protein production is considered a
      multibillion-dollar market, in which about 25% of commercial pharmaceuticals are
      biopharmaceuticals. But to achieve a competitive production process is not an
      easy task. Any production process has to be highly productive, efficient and
      economic. Despite that the perfect host is still not discovered, several research
      groups have chosen Pichia pastoris as expression system for the production of
      their protein because of its many features. The attempt of this review is to
      embrace several research lines that have adopted Pichia pastoris as their
      expression system to produce a protein on an industrial scale in the health care
      industry. 

PMID- 24688489
TI  - Biotechnology of polyketides: new breath of life for the novel antibiotic genetic
      pathways discovery through metagenomics.
AB  - The discovery of secondary metabolites produced by microorganisms (e.g.,
      penicillin in 1928) and the beginning of their industrial application (1940)
      opened new doors to what has been the main medication source for the treatment of
      infectious diseases and tumors. In fact, approximately 80 years after the
      discovery of the first antibiotic compound, and despite all of the warnings about
      the failure of the "goose that laid the golden egg," the potential of this wealth
      is still inexorable: simply adjust the focus from "micro" to "nano", that means
      changing the look from microorganisms to nanograms of DNA. Then, the search for
      new drugs, driven by genetic engineering combined with metagenomic strategies,
      shows us a way to bypass the barriers imposed by methodologies limited to
      isolation and culturing. However, we are far from solving the problem of
      supplying new molecules that are effective against the plasticity of multi- or
      pan-drug-resistant pathogens. Although the first advances in genetic engineering
      date back to 1990, there is still a lack of high-throughput methods to speed up
      the screening of new genes and design new molecules by recombination of pathways.
      In addition, it is necessary an increase in the variety of heterologous hosts and
      improvements throughout the full drug discovery pipeline. Among numerous studies
      focused on this subject, those on polyketide antibiotics stand out for the large
      technical-scientific efforts that established novel solutions for the
      transfer/engineering of major metabolic pathways using transposons and other
      episomes, overcoming one of the main methodological constraints for the
      heterologous expression of major pathways. In silico prediction analysis of three
      dimensional enzymatic structures and advances in sequencing technologies have
      expanded access to the metabolic potential of microorganisms. 

PMID- 24688490
TI  - Anti dermatophytic therapy--prospects for the discovery of new drugs from natural
      products.
AB  - Millions of people and animals suffer from superficial infections caused by a
      group of highly specialized filamentous fungi, the dermatophytes, which only
      infect keratinized structures. With the appearance of AIDS, the incidence of
      dermatophytosis has increased. Current drug therapy used for these infections is
      often toxic, long-term, and expensive and has limited effectiveness; therefore,
      the discovery of new anti dermatophytic compounds is a necessity. Natural
      products have been the most productive source for new drug development. This
      paper provides a brief review of the current literature regarding the presence of
      dermatophytes in immunocompromised patients, drug resistance to conventional
      treatments and new anti dermatophytic treatments. 

PMID- 24688492
TI  - Clavulanic acid production by the MMS 150 mutant obtained from wild type
      Streptomyces clavuligerus ATCC 27064.
AB  - Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes
      produced by bacteria resistants to penicillin and cefalosporin. This molecule is
      produced industrially by strains of Streptomyces clavuligerus in complex media
      which carbon and nitrogen resources are supplied by inexpensive compounds still
      providing high productivity. The genetic production improvement using physical
      and chemical mutagenic agents is an important strategy in programs of industrial
      production development of bioactive metabolites. However, parental strains are
      susceptible to loss of their original productivity due genetic instability
      phenomenona. In this work, some S. clavuligerus mutant strains obtained by
      treatment with UV light and with MMS are compared with the wild type
      (Streptomyces clavuligerus ATCC 27064). The results indicated that the random
      mutations originated some strains with different phenotypes, most divergent
      demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that
      exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150
      presented a larger production of CA when cultivated in semi-synthetics media.
      Using other media, the wild type strain obtained a larger CA production. Besides,
      using the modifed complex media the MMS 150 strain showed changes in its
      lipolitic activity and a larger production of CA. The studies also allowed
      finding the best conditions for a lipase activity exhibited by wild type S.
      clavuligerus and the MMS150 mutant. 

PMID- 24688494
TI  - Statistical investigation of Kluyveromyces lactis cells permeabilization with
      ethanol by response surface methodology.
AB  - The aim of our study was to select the optimal operating conditions to
      permeabilize Kluyveromyces lactis cells using ethanol as a solvent as an
      alternative to cell disruption and extraction. Cell permeabilization was carried
      out by a non-mechanical method consisting of chemical treatment with ethanol, and
      the results were expressed as beta-galactosidase activity. Experiments were
      conducted under different conditions of ethanol concentration, treatment time and
      temperature according to a central composite rotatable design (CCRD), and the
      collected results were then worked out by response surface methodology (RSM).
      Cell permeabilization was improved by an increase in ethanol concentration and
      simultaneous decreases in the incubation temperature and treatment time. Such an
      approach allowed us to identify an optimal range of the independent variables
      within which the beta-galactosidase activity was optimized. A maximum
      permeabilization of 2,816 mmol L(-1) oNP min(-1) g(-1) was obtained by treating
      cells with 75.0% v/v of ethanol at 20.0  degrees C for 15.0 min. The proposed
      methodology resulted to be effective and suited for K. lactis cells
      permeabilization at a lab-scale and promises to be of possible interest for
      future applications mainly in the food industry. 

PMID- 24688493
TI  - Extracellular polysaccharide production by a strain of Pleurotus djamor isolated
      in the south of Brazil and antitumor activity on Sarcoma 180.
AB  - Polysaccharides with medicinal properties can be obtained from fruiting bodies,
      mycelium and culture broth of several fungus species. This work was carried out
      in batch culture using a stirred tank reactor with two different initial glucose
      concentrations (40-50 g/L) and pH values (3.0-4.0) to enhance extracellular
      polysaccharides production by Pleurotus djamor UNIVILLE 001 and evaluate
      antitumor effect of intraperitonial administration of Pleurotus djamor extract on
      sarcoma 180 animal model. According to factorial design, the low pH value (pH
      3.0) led to a gain of 1.6 g/L on the extracellular polysaccharide concentration,
      while glucose concentration in the tested range had no significant effect on the
      concentration of polysaccharide. With 40 g/L initial glucose concentration and pH
      3.0, it was observed that yield factor of extracellular polysaccharide on
      substrate (YP/S = 0.072) and maximum extracellular polysaccharide productivity
      (Q(Pmax) = 11.26 mg/L.h) were about 188% and 321% respectively higher than those
      obtained in the experiment performed at pH 4.0. Under these conditions, the
      highest values of the yield factor of biomass on substrate (YX/S = 0.24) and
      maximal biomass productivity (Q(Xmax) = 32.2 mg/L.h) were also reached. In tumor
      response study, mean tumor volume on the 21th day was 35.3 cm(3) in untreated
      group and 1.6 cm(3) in treated group (p = 0.05) with a tumor inhibition rate of
      94%. These impressive results suggests an inhibitory effect of P.djamor extract
      on cancer cells.

PMID- 24688495
TI  - Bioconversion of R-(+)-limonene to perillic acid by the yeast Yarrowia
      lipolytica.
AB  - Perillyl derivatives are increasingly important due to their flavouring and
      antimicrobial properties as well as their potential as anticancer agents. These
      terpenoid species, which are present in limited amounts in plants, may be
      obtained via bioconversion of selected monoterpene hydrocarbons. In this study,
      seventeen yeast strains were screened for their ability to oxidize the exocyclic
      methyl group in the p-menthene moiety of limonene into perillic acid. Of the
      yeast tested, the highest efficiency was observed for Yarrowia lipolytica ATCC
      18942. The conversion of R (+)-limonene by Y. lipolytica was evaluated by varying
      the pH (3 to 8) and the temperature (25 to 30  degrees C) in a reaction medium
      containing 0.5% v/v limonene and 10 g/L of stationary phase cells (dry weight).
      The best results, corresponding to 564 mg/L of perillic acid, were obtained in
      buffered medium at pH 7.1 that was incubated at 25  degrees C for 48 h. The
      stepwise addition of limonene increased the perillic acid concentration by over
      50%, reaching 855 mg/L, whereas the addition of glucose or surfactant to the
      reaction medium did not improve the bioconversion process. The use of Y.
      lipolytica showed promise for ease of further downstream processing, as perillic
      acid was the sole oxidised product of the bioconversion reaction. Moreover,
      bioprocesses using safe and easy to cultivate yeast cells have been favoured in
      industry. 

PMID- 24688496
TI  - Extraction and in vitro antioxidant activity of exopolysaccharide by Pleurotus
      eryngii SI-02.
AB  - The extraction parameters for Pleurotus eryngii SI-02 exopolysaccharide (EPS)
      produced during submerged culture were optimized using response surface
      methodology (RSM). The optimum conditions for EPS extraction were predicted to
      be, precipitation time 20.24 h, ethanol concentration 89.62% and pH 8.17, and EPS
      production was estimated at 7.27 g/L. The actual yield of EPS under these
      conditions was 7.21 g/L. The in vitro antioxidant results of the EPS showed that
      the inhibition effects of EPS at a dosage of 400 mg/L on hydroxyl, superoxide
      anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were 59.63 +/- 3.72%,
      38.69 +/- 2.59%, and 66.36 +/- 4.42%, respectively, which were 12.74 +/- 1.03%,
      8.01 +/- 0.56%, and 12.19 +/- 1.05% higher than that of butylated hydroxytoluene
      (BHT), respectively. The reducing power of EPS of P. eryngii SI-02 was 0.98 +/-
      0.05, 60.66 +/- 5.14% higher than that of BHT. The results provide a reference
      for large-scale production of EPS by P. eryngii SI-02 in industrial fermentation
      and the EPS can be used as a potential antioxidant which enhances adaptive immune
      responses. 

PMID- 24688497
TI  - Enhanced production of Aspergillus tamarii lipase for recovery of fat from
      tannery fleshings.
AB  - The influence of various oil cakes has been investigated for high level
      production of lipase using Aspergillus tamarii MTCC 5152. By solid state
      fermentation in wheat bran containing 2.5% w/w gingili oil cake at 70% v/w
      moisture content the fungus produced a maximal yield of lipase (758 +/- 3.61 u/g)
      after 5 days of incubation using 2% v/w inoculum containing 10(6) spores/mL.
      Wheat bran and gingili oil cake with supplementation of gingili oil (1.0% w/w),
      glucose (0.5% w/w) and peptone (0.5% w/w) gives an increased enzyme production of
      793 +/- 6.56 u/g. The enzyme shows maximum activity at pH 7.0, temperature 50 
      degrees C and was stable between the pH 5.0-8.0 and temperature up to 60  degrees
      C. Crude lipase (3%) applied to tannery fleshing shows 92% fat solubility. The
      results demonstrate that fat obtained from tannery fleshing, a by-product of the
      leather industry has a high potential for biodiesel production and the
      proteinaceous residue obtained can be used as animal feed. 

PMID- 24688498
TI  - Cashew apple juice as microbial cultivation medium for non-immunogenic hyaluronic
      acid production.
AB  - In this work, natural cashew apple juice was used as cultivation medium as an
      alternative to substitute brain heart infusion medium. The effect of aeration and
      juice supplementation with yeast extract on the production of hyaluronic acid in
      batch fermentation was also investigated. Similar levels of cell mass were
      obtained in inoculum using cashew apple juice supplemented with yeast extract or
      the conventional brain heart infusion medium. Fermentation in Erlenmeyer flasks
      produced low biomass and hyaluronic acid concentrations. The hyaluronic acid
      concentration and viscosity increased from 0.15 g/L and 3.87 cP (no aeration or
      medium supplementation) to 1.76 g/L and 107 cP, when aeration (2 vvm) and 60 g/L
      of yeast extract were used. The results suggest the production of low-molecular
      weight hyaluronic acid oligomers instead of the high molecular weight polymer. 

PMID- 24688499
TI  - Kinetic characterization of glucose aerodehydrogenase from Aspergillus niger EMS
      150-F after optimizing the dose of mutagen for enhanced production of enzyme.
AB  - In the present study enhanced production of glucose aerodehydrogenase from
      Aspergillus niger has been achieved after optimizing the dose of chemical mutagen
      ethyl methane sulfonate (EMS) that has not been reported earlier. Different doses
      of mutagen were applied and a strain was developed basing upon the best
      production. The selected strain Aspergillus niger EMS-150-F was optimized for
      nutrient requirements in order to produce enzyme through fermentation and the
      results showed the best yield at 2% corn steep liquor (CSL), 36 hours
      fermentation time, pH 5, 30  degrees C temperature, 0.3% KH2PO4, 0.3% urea and
      0.06% CaCO3. The enzyme was then purified and resulted in 57.88 fold purification
      with 52.12% recovery. On kinetic characterization, the enzyme showed optimum
      activity at pH 6 and temperature 30  degrees C. The Michaelis-Menton constants
      (K(m), Vmax, Kcat and Kcat/K(m)) were 20 mM, 45.87 U mL(-1), 1118.81 s(-1) and
      55.94 s(-1) mM(-1), respectively. The enzyme was found to be thermally stable and
      the enthalpy and free energy showed an increase with increase in temperature and
      DeltaS* was highly negative proving the enzyme from A. niger EMS-150-F resistant
      to temperature and showing a very little disorderliness.

PMID- 24688500
TI  - Isolation and characterization of novel thermophilic lipase-secreting bacteria.
AB  - The purpose of the present study was to screen and identify the lipase-producing
      microorganisms from various regions of Iran. Samples collected from hot spring,
      Persian Gulf, desert area and oil-contaminated soil, were analyzed for
      thermophilic extracellular-lipase producing organisms. Six strains with high
      activity on rhodamine B plates were selected for chemical identification and
      further study. Among these isolated bacteria, four strains show higher activity
      in pH-Stat method at 55  degrees C. These strains were identified by PCR
      amplification of 16s rRNA genes using universal primers. Fermentation increased
      the activity up to 50%. The growth medium, designed for lipase production,
      increased the activity up to 4.55 folds. The crude supernatant of ZR-5 after
      fermentation and separation the cells, was lyophilized and the activity was
      measured. Total activity of this strain was 12 kU/g that shows its potential for
      industrial uses. Further study is required for purification of enzyme and
      calculation its specific activity. Immobilization is another approach should be
      considered. 

PMID- 24688501
TI  - Characteristics of Saccharomyces cerevisiae yeasts exhibiting rough colonies and
      pseudohyphal morphology with respect to alcoholic fermentation.
AB  - Among the native yeasts found in alcoholic fermentation, rough colonies
      associated with pseudohyphal morphology belonging to the species Saccharomyces
      cerevisiae are very common and undesirable during the process. The aim of this
      work was to perform morphological and physiological characterisations of S.
      cerevisiae strains that exhibited rough and smooth colonies in an attempt to
      identify alternatives that could contribute to the management of rough colony
      yeasts in alcoholic fermentation. Characterisation tests for invasiveness in Agar
      medium, killer activity, flocculation and fermentative capacity were performed on
      22 strains (11 rough and 11 smooth colonies). The effects of acid treatment at
      different pH values on the growth of two strains ("52"--rough and "PE-02"-
      smooth) as well as batch fermentation tests with cell recycling and acid
      treatment of the cells were also evaluated. Invasiveness in YPD Agar medium
      occurred at low frequency; ten of eleven rough yeasts exhibited flocculation;
      none of the strains showed killer activity; and the rough strains presented lower
      and slower fermentative capacities compared to the smooth strains in a 48-h cycle
      in a batch system with sugar cane juice. The growth of the rough strain was
      severely affected by the acid treatment at pH values of 1.0 and 1.5; however, the
      growth of the smooth strain was not affected. The fermentative efficiency in
      mixed fermentation (smooth and rough strains in the same cell mass proportion)
      did not differ from the efficiency obtained with the smooth strain alone, most
      likely because the acid treatment was conducted at pH 1.5 in a batch cell-recycle
      test. A fermentative efficiency as low as 60% was observed with the rough colony
      alone.

PMID- 24688502
TI  - Chemicals and lemon essential oil effect on Alicyclobacillus acidoterrestris
      viability.
AB  - Alicyclobacillus acidoterrestris is considered to be one of the important target
      microorganisms in the quality control of acidic canned foods. There is an urgent
      need to develop a suitable method for inhibiting or controlling the germination
      and outgrowth of A.acidoterrestris in acidic drinks. The aim of this work was to
      evaluate the chemicals used in the lemon industry (sodium benzoate, potassium
      sorbate), and lemon essential oil as a natural compound, against a strain of
      A.acidoterrestris in MEB medium and in lemon juice concentrate. The results
      pointed out that sodium benzoate (500-1000-2000 ppm) and lemon essential oil
      (0.08-0.12-0.16%) completely inhibited the germination of A. acidoterrestris
      spores in MEB medium and LJC for 11 days. Potassium sorbate (600-1200 ppm) was
      more effective to inhibit the growth of the microbial target in lemon juice than
      in MEB medium. The effect of sodium benzoate, potassium sorbate and essential oil
      was sporostatic in MEB and LJC as they did not affect spore viability. 

PMID- 24688503
TI  - Dynamics of the chemical composition and productivity of composts for the
      cultivation of Agaricus bisporus strains.
AB  - Two compost formulations based on oat straw (Avena sativa) and brachiaria
      (Brachiaria sp.) were tested for the cultivation of three Agaricus bisporus
      strains (ABI-07/06, ABI-05/03, and PB-1). The experimental design was a 2 * 3
      factorial scheme (composts * strains) with 6 treatments and 8 repetitions (boxes
      containing 12 kg of compost). The chemical characterization of the compost
      (humidity, organic matter, carbon, nitrogen, pH, raw protein, ethereal extract,
      fibers, ash, cellulose, hemicellulose, and lignin) before and after the
      cultivation of A. bisporus and the production (basidiomata mass, productivity,
      and biological efficiency) were evaluated. Data were submitted to variance
      analysis, and averages were compared by means of the Tukey's test. According to
      the results obtained, the chemical and production characteristics showed that the
      best performances for the cultivation of A. bisporus were presented by the
      compost based on oat and the strain ABI-07/06. 

PMID- 24688504
TI  - Elimination of coliforms and Salmonella spp. in sheep meat by gamma irradiation
      treatment.
AB  - This study aimed at evaluating the bacteriological effects of the treatment of
      sheep meat contaminated with total coliforms, coliforms at 45  degrees C and
      Salmonella spp. by using irradiation at doses of 3 kGy and 5 kGy. Thirty sheep
      meat samples were collected from animals located in Rio de Janeiro State, Brazil,
      and then grouped in three lots including 10 samples: non-irradiated (control);
      irradiated with 3 kGy; and irradiated with 5 kGy. Exposure to gamma radiation in
      a (137)Cs source-driven irradiating facility was performed at the Nuclear Defense
      Section of the Brazilian Army Technological Center (CTEx) in Rio de Janeiro. The
      samples were kept under freezing temperature (-18  degrees C) until the analyses,
      which occurred in two and four months after irradiation. The results were
      interpreted by comparison with the standards of the current legislation and
      demonstrated that non-irradiated samples were outside the parameters established
      by law for all groups of bacteria studied. Gamma irradiation was effective in
      inactivating those microorganisms at both doses tested and the optimal dose was
      achieved at 3 kGy. The results have shown not only the need for sanitary
      conditions improvements in slaughter and processing of sheep meat but also the
      irradiation effectiveness to eliminate coliform bacteria and Salmonella spp.

PMID- 24688505
TI  - Presence of enterotoxigenic Staphylococcus aureus in artisan fruit salads in the
      city of San Luis, Argentina.
AB  - An increase in the consumption of fruit juices and minimally processed fruits
      salads has been observed in recent years all over the world. In this work, the
      microbiological quality of artisan fruit salads was analysed. Faecal coliforms,
      Salmonella spp, Shigella spp, Yersinia enterocolitica and Escherichia coli
      O157:H7 were not detected; nevertheless, eleven strains of Staphylococcus aureus
      were isolated. By multiplex PCR, all isolates showed positive results for S.
      aureus 16S rRNA gene and 63.6% of them were positive for sea gene. Furthermore,
      PCR sea positive strains were able to produce the corresponding enterotoxin.
      Finally, the inactivation of these strains in fruit salads by nisin, lysozyme and
      EDTA, was studied. EDTA produced a total S. aureus growth inhibition after 60 h
      of incubation at a concentration of 250 mg/L. The presence of S. aureus might
      indicate inadequate hygiene conditions during salad elaboration; however, the
      enterotoxigenicity of the strains isolated in this study, highlights the risk of
      consumers' intoxication. EDTA could be used to inhibit the growth of S. aureus in
      artisan fruit salads and extend the shelf life of these products. 

PMID- 24688506
TI  - Antibacterial activity of bacteriocin-like substance P34 on Listeria
      monocytogenes in chicken sausage.
AB  - The antimicrobial activity of the bacteriocin-like substance (BLS) P34 against
      Listeria monocytogenes was investigated in chicken sausage. The BLS was applied
      to chicken sausages (256 AU g(-1)) previously inoculated with a suspension of
      10(2) cfu g(-1) of L. monocytogenes. BLS P34 inhibited the indicator
      microorganism in situ in all incubation times for up to 10 days at 5  degrees C.
      The effectiveness of BLS P34 was increased when it was added in combination with
      nisin. The bacteriocin was also tested in natural eatable natural bovine wrapping
      (salty semi-dried tripe) against the same indicator microorganism, also showing
      inhibitory capability in vitro. BLS P34 showed potential to control L.
      monocytogenes in refrigerated meat products. 

PMID- 24688507
TI  - Prevalence and quantification of Listeria monocytogenes in beef offal at retail
      level in Selangor, Malaysia.
AB  - A total of 63 beef offal samples (beef liver = 16; beef lung = 14; beef intestine
      = 9; beef tripe = 15; beef spleen = 9) from three wet markets (A, B, and C) in
      Selangor, Malaysia were examined for the prevalence and microbial load of
      Listeria monocytogenes. A combination of the most probable number and polymerase
      chain reaction (MPN-PCR) method was employed in this study. It was found that L.
      monocytogenes detected in 33.33% of the beef offal samples. The prevalence of L.
      monocytogenes in beef offal purchased from wet markets A, B, and C were 22.73%,
      37.50% and 41.18% respectively. The density of L. monocytogenes in all the
      samples ranged from < 3 up to > 2,400 MPN/g. The findings in this study indicate
      that beef offal can be a potential vehicle of foodborne listeriosis. 

PMID- 24688509
TI  - Essential oils of thyme and Rosemary in the control of Listeria monocytogenes in
      raw beef.
AB  - This study was developed in order to evaluate two alternatives for the control of
      Listeria monocytogenes in raw bovine meat pieces, both based on the use of Thymus
      vulgaris and Rosmarinus officinalis essential oils (EOs). The antilisterial
      activity of different concentrations of the EOs was tested in vitro using agar
      dilution and disk volatilization techniques. In addition, L. monocytogenes was
      inoculated in meat pieces, which were submerged in edible gelatin coatings
      containing 2% (v/v) EOs or submitted to the vapor of EOs (0.74 MUL.cm(-3)). L.
      monocytogenes was quantified after one, 48 and 96 hours of storage (7  degrees
      C). In the in vitro tests, the EO of T. vulgaris presented higher activity. The
      two options used (edible gelatin coating and vapor activity), in spite of
      exercising effects with differentiated behaviors, presented antibacterial
      activity against L. monocytogenes inoculated in raw bovine meat (p < 0.05).
      Greatest antibacterial activity were obtained in the experiment that used edible
      coatings containing EOs, at 48 hours of storage reductions in bacterial counts
      between 1.09 and 1.25 Log CFU.g(-1) were obtained. In the vapor effect
      experiment, the EO of T. vulgaris caused the highest reduction in the population
      of bacteria inoculated in raw bovine meat (p < 0.05), 0.40 Log CFU.g(-1) at 96
      hours of storage. This study supplied important information regarding new and
      promising natural alternatives, based on the concept of active packaging, for the
      control of L. monocytogenes in the meat industry. 

PMID- 24688508
TI  - Virulence profiles of Shiga Toxin-Producing Escherichia coli and other
      potentially diarrheagenic E.coli of bovine origin, in Mendoza, Argentina.
AB  - This study described a group of strains obtained from a slaughter house in
      Mendoza, in terms of their pathogenic factors, serotype, antibiotype and
      molecular profile. Ninety one rectal swabs and one hundred eight plating samples
      taken from carcasses of healthy cattle intended for meat consumption were
      analyzed. Both the swab and the plate samples were processed to analyze the
      samples for the presence of virulence genes by PCR: stx1, stx2, eae and astA. The
      Stx positive strains were confirmed by citotoxicity assay in Vero cells. The
      isolates were subsequently investigated for their O:H serotype, antimicrobial
      susceptibility and molecular profile by Random Amplification of Polymorphic DNA
      (RAPD). Twelve E.coli strains were identified by their pathogenicity. Nine were
      from fecal origin and three from carcasses. Three strains carried the stx1 gene,
      three the stx2 gene, two carried eae and four the astA gene. The detected
      serotypes were: O172:H-; O150:H8; O91:H21; O178:H19 and O2:H5. The strains showed
      a similarity around 70% by RAPD. Some of the E.coli strains belonged to
      serogroups known for certain life-threatening diseases in humans. Their presence
      in carcasses indicates the high probability of bacterial spread during slaughter
      and processing. 

PMID- 24688510
TI  - The sensitivity of bacterial foodborne pathogens to Croton blanchetianus Baill
      essential oil.
AB  - The aim of this study was to assess the activity of essential oil extracted from
      the leaves of C. blanchetianus Baill, popularly known as "marmeleiro", in
      inhibiting the growth and survival of pathogenic microorganisms in food by
      determining their survival in vitro and by observing the behaviour of Listeria
      monocytogenes inoculated into a food model (meat cubes) that was stored at
      refrigeration temperature (7 +/- 1  degrees C) for 4 days. The results indicated
      a bactericidal effect against Aeromonas hydrophila and Listeria monocytogenes and
      bacteriostatic action against Salmonella Enteritidis. A bacteriostatic effect on
      meat contaminated with L. monocytogenes was found for all concentrations of
      essential oils tested. These results showed that essential oil from the leaves of
      C. blanchetianus Baill represents an alternative source of potentially natural
      antimicrobial agents that may be used as a food preservative. 

PMID- 24688511
TI  - Gene detection and toxin production evaluation of hemolysin BL of Bacillus cereus
      isolated from milk and dairy products marketed in Brazil.
AB  - Bacillus cereusis an ubiquitous, spore-forming bacteria that can survive
      pasteurization and the majority of the heating processes used in the dairy
      industry. Besides, it is a pathogen responsible for different types of food
      poisoning. One type of foodborne disease caused by B.cereusis the diarrheal
      syndrome, which is caused by the ingestion of vegetative cells producing toxins
      in the small intestine. One virulence factor for the diarrheal syndrome is the
      toxin hemolysin BL (HBL), a three-component protein formed by the L1, L2 and B
      components. In order to evaluate the presence of diarrheal strains isolated from
      milk and dairy products, 63 B. cereus isolates were obtained from 260 samples of
      UHT milk, pasteurized milk and powdered milk, sold in commercial establishments
      and from different brands. The isolates were subjected to the Polymerase Chain
      Reaction (PCR) for the detection of the encoding genes for the L1, L2 and B
      components and the toxin production capacity were evaluated with an immunoassay.
      A total of 23 [36.5%] isolates were identified carrying simultaneously the three
      tested genes, from which, 20 [86.9%] showed toxigenic capacity. 26 [41.3%]
      isolates did not carry any of genes tested and the other 14 [22.2%] were positive
      for one or two of them. The results showed a high toxigenic capacity among the B.
      cereus isolates able to produce the HBL, indicating a potential risk for
      consumers. 

PMID- 24688512
TI  - Molecular characterization of lactobacilli isolated from fermented idli batter.
AB  - Lactic acid bacteria are non pathogenic organism widely distributed in nature
      typically involved in a large number of spontaneous food fermentation. The
      purpose of this study was to characterize the bacteriocinogenic lactobacilli from
      fermented idli batter which can find application in biopreservation and
      biomedicine. Eight most promising lactobacilli were chosen from twenty two
      isolates based on their spectrum of activity against other lactic acid bacteria
      and pathogens. The eight lactobacilli were characterized based on the various
      classical phenotypic tests, physiological tests and biochemical tests including
      various carbohydrate utilization profiles. All isolates were homo fermentative,
      catalase, and gelatin negative. Molecular characterization was performed by RAPD,
      16S rRNA analysis, 16S ARDRA, and Multiplex PCR for species identification. RAPD
      was carried out using the primer R2 and M13. Five different clusters were
      obtained based on RAPD indicating strain level variation. 16S rRNA analysis
      showed 99 to 100% homology towards Lactobacillus plantarum. The restriction
      digestion pattern was similar for all the isolates with the restriction enzyme
      AluI. The subspecies were identified by performing Multiplex PCR using species
      specific primer. Among the five clusters, three clusters were clearly identified
      as Lactobacillus plantarum subsp. plantarum, Lactobacillus pentosus, and
      Lactobacillus plantarum subsp. argentoratensis. 

PMID- 24688513
TI  - Halotolerance, ligninase production and herbicide degradation ability of
      basidiomycetes strains.
AB  - Fungi have been recently recognized as organisms able to grow in presence of high
      salt concentration with halophilic and halotolerance properties and their
      ligninolytic enzyme complex have an unspecific action enabling their use to
      degradation of a number of xenobiotic compounds. In this work, both the effect of
      salt and polyols on growth of the basidiomycetes strains, on their ability to
      produce ligninolytic enzyme and diuron degradation were evaluated. Results showed
      that the presence of NaCl in the culture medium affected fungal specimens in
      different ways. Seven out of ten tested strains had growth inhibited by salt
      while Dacryopinax elegans SXS323, Polyporus sp MCA128 and Datronia stereoides
      MCA167 fungi exhibited higher biomass production in medium containing 0.5 and 0.6
      mol.L(-1) of NaCl, suggesting to be halotolerant. Polyols such as glycerol and
      mannitol added into the culture media improved the biomass and ligninases
      production by D. elegans but the fungus did not reveal consumption of these
      polyols from media. This fungus degraded diuron in medium control, in presence of
      NaCl as well as polyols, produced MnP, LiP and laccase. 

PMID- 24688514
TI  - Expression of enterovirus 71 capsid protein VP1 in Escherichia coli and its
      clinical application.
AB  - The VPl gene of enterovirus 71 (EV71) was synthesized, construct a recombinant
      plasmid pET15b/VP1 and expressed in E. coli BL21. The recombinant VP1 protein
      could specifically react with EV71-infected patient sera without the cross
      reaction with serum antibodies of coxsackievirus A16 (CA16), A4, A5, B3 and B5 as
      well as echovirus 6. In acute and convalescent phases, IgM and IgG antibodies of
      182 serum samples were detected by ELISA with recombinant VP1 protein as a coated
      antigen. The results showed that the sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of IgM antibodies in
      serum samples for the diagnosis of EV71 infection were 90.1, 98.4, 98.8 and
      88.7%, respectively; similarly, those of IgG antibodies in serum samples were
      82.4, 89.1, 91.5 and 78.1%, respectively. Five of 80 samples (6.25%) from CA16
      infected patients were detected positive by ELISA with recombinant VP1 protein in
      which indicated the cross reactions and 0 of 5 samples from patients infected
      with other enteroviruses including CA4, CA5, CB3, CB5 and echovirus 6. Therefore,
      the recombinant VP1 protein of EV7l may provide a theoretical reference for
      establishing an effective antibody screening of IgM for EV71-infected patients
      with clinically suspected hand, foot, and mouth disease (HFMD). 

PMID- 24688515
TI  - Prevalence of virulence genes in strains of Campylobacter jejuni isolated from
      human, bovine and broiler.
AB  - Campylobacter jejuni isolates of different origins (bovine, broiler meat, human)
      were screened by polymerase chain reaction for the presence of 4 genes cdtB, cst
      II, ggt, and virB11, previously linked to virulence such as adherence, invasion,
      colonization, molecular mimicry, and cytotoxin production. In addition, the
      isolates were screened for the presence of the global gene regulator csrA linked
      to oxidative stress responses, biofilms formation, and cell adhesion. All the C.
      jejuni isolates were positive for cdtB gene. The csrA gene was detected in 100%
      and 92% of C. jejuni isolates from human and animal origin and the virB11 gene
      was detected in 7.3% and 3.6% isolates from chicken and human respectively. All
      isolates from bovine were negative for the virB11 gene. The isolates showed a
      wide variation for the presence of the remaining genes. Of the C. jejuni
      recovered from human 83.6%, and 32.7% were positive for cst-II, and ggt
      respectively. Out of the isolates from chicken 40% and 5.5% isolates revealed the
      presence of cst-II, and ggt, respectively. Finally of the C. jejuni isolates from
      bovine, 97.7% and 22.7% were positive for cst-II, and ggt respectively. We
      conclude that the genes of this study circulate among humans and animals. These
      results led us to hypothesize that the isolates associated with enteritis (cdtB
      positives) are not selected by environmental or host-specific factors. On the
      other hand, the high frequencies of csrA gene in C. jejuni show that this gene is
      important for the survival of C. jejuni in animals and humans. 

PMID- 24688516
TI  - Histopathology of cotton bollworm midgut infected with Helicoverpa armigera
      cytoplasmic polyhedrosis virus.
AB  - This research was carried out to examine cytopathological effects of Helicoverpa
      armigera Cytoplasmic polyhedrosis virus (HaCPV) on infected midgut cotton
      bollworm (Helicoverpa armigera) using transmission and scanning electron
      microscope. The symptoms on infected host larvae of the host, compared with
      healthy ones, were getting swollen with milky-white and fragile Histopathological
      examinations showed infection with HaCPV small polyhedral inclusion bodies (PIB)
      after 1 or 2 days which were observed in columnar cells of midgut. Virions were
      partially or completely occupied in a polyhedral matrix to form polyhedral
      inclusion bodies (PIB) at periphery of virogenic stroma. PIBs were measured 0.5
      to 3.5 MUm and virions about 46 nm in diameter. Microvilli of infected columnar
      cells were affected and degenerated immediately prior to rupture of the cell.
      Some infected columnar cells ruptured to release PIB into the gut lumen 3 days
      after infection. In addition, PIB were found in goblet cells, 5 or 6 days after
      infection. Infected goblet cells degenerate to such an extent that only a few of
      the original microvillus-like cytoplasmic projections and cell organells were
      left. These cytopathic effects caused in the midgut by HaCPV on cotton bollworm
      larvae are essentially similar to those have been reported for lepidoperan and
      dipteran infection by CPV. 

PMID- 24688517
TI  - Seroprevalence of Hepatitis B and C markers at the population level in the
      municipality of Caxias do Sul, southern Brazil.
AB  - Chronic viral hepatitis are main public health problems worldwide. Data about the
      seroprevalence to Hepatitis B and C viruses (HBV e HCV) at the population level
      are scarce on Brazil and especially for the Southern region of the country. The
      seroprevalence to HBV and HBC antigens was evaluated on a large portion of the
      population of the municipality of Caxias do Sul (427,858 inhabitants), Brazil. A
      total of 60,604 individual serum samples collected from 2008 to 2011 were
      screened for HBV surface antigen (HBsAg) and for antibodies against HBsAg; anti
      HCV antibodies were measured by ELISA (Enzyme Linked Immunosorbent Assay).
      Overall, 1.63% of the individuals were positive for HBsAg and 1.43% showed
      seropositivity to HCV. From the total, 31,749 samples were analyzed for HBsAg and
      28,855 for HCV. For HBsAg, 519 samples showed positive (1.63%) while the results
      for 37 patients (0.12%) remained inconclusive. For the anti-HCV test, 412
      individuals (1.43%) showed positive. From the positive samples for HBsAg 216
      (50.6%) were from male individuals whereas for anti-HCV the seroprevalence was
      slightly higher for females 216 (52.4%). The higher prevalence for both hepatitis
      viruses were found among individuals at the age group of 40 to 59 years and the
      lower levels of positivity for both HBV and HBC were among children and
      teenagers. 

PMID- 24688518
TI  - Cgl-SLT2 is required for appressorium formation, sporulation and pathogenicity in
      Colletotrichum gloeosporioides.
AB  - The mitogen-activated protein (MAP) kinase pathways has been implicated in the
      pathogenicity of various pathogenic fungi and plays important roles in regulating
      pathogenicity-related morphogenesis. This work describes the isolation and
      characterization of MAP kinase gene, Cgl-SLT2, from Colletotrichum
      gloeosporioides. A DNA sequence, including 1,633 bp of Cgl-SLT2 open-reading
      frame and its promoter and terminator regions, was isolated via DNA walking and
      cloned. To analyze gene function, a gene disruption cassette containing
      hygromycin-resistant gene was constructed, and Cgl-SLT2 was inactivated via gene
      deletion. Analysis on Cgl-slt2 mutant revealed a defect in vegetative growth and
      sporulation as compared to the wild-type strain. When grown under nutrient
      limiting conditions, hyperbranched hyphal morphology was observed in the mutant.
      Conidia induction for germination on rubber wax-coated hard surfaces revealed no
      differences in the percentage of conidial germination between the wild-type and
      Cgl-slt2 mutant. However, the percentage of appressorium formation in the mutant
      was greatly reduced. Bipolar germination in the mutant was higher than in the
      wild-type at 8-h post-induction. A pathogenicity assay revealed that the mutant
      was unable to infect either wounded or unwounded mangoes. These results suggest
      that the Cgl-SLT2 MAP kinase is required for C. gloeosporioides conidiation,
      polarized growth, appressorium formation and pathogenicity. 

PMID- 24688519
TI  - Mycobacterium tuberculosis belonging to family LAM and sublineage RD(Rio): common
      strains in Southern Brazil for over 10 years.
AB  - A sublineage of Mycobacterium tuberculosis called RD(Rio) was described in 2007.
      Although only recently described, this strain may have been present previously in
      the population, and its identification in clinical isolates will elucidate
      bacterial transmission dynamics and host-pathogen interactions. This study
      evaluated the clonal diversity of the RD(Rio) sublineage in clinical isolates
      from Rio Grande-RS obtained between 1998 and 2001. Among the 45 samples analyzed
      by the MIRU-VNTR method, there were six clusters with two samples each and 33
      orphan strains with unique pattern. The strains were distributed across several
      different lineages including LAM (34.04%), * (14.89%), Haarlem (12.77%), UgandaI
      (10.64%), S (4.26%), NEW-1 (2.13%) and Cameroon (2.13%); 14.89% of the strains
      matched to multiple lineages. RD(Rio) strains were present in 28.9% of the
      samples and 81.25% of the identified strains belonged to the LAM family. The high
      clonal diversity observed in this study is a constant feature in this region. The
      RD(Rio) sublineage has been in Rio Grande-RS since 1998. The continued monitoring
      of RD(Rio) in clinical isolates will enhance the understanding of its
      epidemiological significance. 

PMID- 24688520
TI  - Use of the VITEK 2 system to identify and test the antifungal susceptibility of
      clinically relevant yeast species.
AB  - Eleven quality control isolates (Candida albicans ATCC 64548, C. tropicalis ATCC
      200956, C. glabrata ATCC 90030, C. lusitaniae ATCC 200951, C. parapsilosis ATCC
      22019, C. krusei ATCC 6258, C. dubliniensis ATCC 6330, Saccharomyces cerevisiae
      ATCC 9763, Cryptococcus neoformans ATCC 90012, C. gattii FIOCRUZ-CPF 60, and
      Trichosporon mucoides ATCC 204094) and 32 bloodstream isolates, including C.
      albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, C.
      guilliermondii, C. pelliculosa (Pichia anomala), C. haemulonii, C. lusitaniae,
      and C. kefyr were identified at the species level by the VITEK 2 system. A set of
      clinical isolates (32 total) were used as challenge strains to evaluate the
      ability of the VITEK 2 system to determine the antifungal susceptibility of
      yeasts compared with the CLSI and EUCAST BMD reference standards. The VITEK 2
      system correctly identified 100% of the challenge strains. The identification of
      yeast species and the evaluation of their susceptibility profiles were performed
      in an automated manner by the VITEK 2 system after approximately 15 h of growth
      for most species of Candida. The VITEK 2 system ensures that each test is
      performed in a standardized manner and provides quantitative MIC results that are
      reproducible and accurate when compared with the BMD reference methods. This
      system was able to determine the MICs of amphotericin B, flucytosine,
      voriconazole, and fluconazole in 15 h or less for the most common clinically
      relevant Candida species. In addition, the VITEK 2 system could reliably identify
      resistance to flucytosine, voriconazole, and fluconazole and exhibits excellent
      quantitative and qualitative agreement with the CLSI or EUCAST broth
      microdilution reference methods. 

PMID- 24688521
TI  - Investigation of the association between clinical outcome and the cag
      pathogenicity-island and other virulence genes of Helicobacter pylori isolates
      from patients with dyspepsia in Eastern Turkey.
AB  - The aims of our work were to determine the presence of the cag pathogenicity
      island (cag PAI) and other virulence genes of Helicobacter pylori recovered from
      patients with gastritis and peptic ulcer, and to investigate the correlation of
      these virulence genes with clinical outcome. The presence of the cagA, the
      promoter regions of cagA, cagE, cagT, and the left end of cag-PAI (LEC), cag
      right junction (cagRJ), the plasticity region open reading frames (ORFs), vacA
      and oipA genes among 69 H. pylori isolates were determined by polymerase chain
      reaction. Intact cag PAI was detected in only one (1.4%) isolate. The cagA gene
      was identified in 52.1% and 76.2% of isolates from patients with dyspepsia
      (gastritis and peptic ulcer), respectively. The plasticity region ORFs i.e.
      JHP912 and JHP931 were predominantly detected in isolates from peptic ulcer. Less
      than 25% of the isolates carried other ORFs. Types I, II and III were the most
      commonly found among the isolates. None of the isolates possessed type Ib, 1c,
      IIIb, IV and V motifs. The most commonly vacA genotypes were s1am1a and s1m2 in
      isolates with peptic ulcer and gastritis, respectively. The results confirmed
      that the prevalence of oipA (Hp0638) gene was 75% and 85.7% in patients with
      gastritis and peptic ulcer, respectively. Furthermore, vacA s1am1a positivity was
      significantly related to peptic ulcer (p < 0.05). 

PMID- 24688523
TI  - Characterization of mercury-resistant clinical Aeromonas species.
AB  - Mercury-resistant Aeromonas strains isolated from diarrhea were studied.
      Resistance occurs via mercuric ion reduction but merA and merR genes were only
      detected in some strains using PCR and dot hybridization. Results indicate a high
      variability in mer operons in Aeromonas. To our knowledge, this is the first
      report of mercury-resistant clinical Aeromonas strains. 

PMID- 24688522
TI  - Antifungal activity of extracts from Piper aduncum leaves prepared by different
      solvents and extraction techniques against dermatophytes Trichophyton rubrum and
      Trichophyton interdigitale.
AB  - The effects of different solvents and extraction techniques upon the
      phytochemical profile and anti-Trichophyton activity of extracts from Piper
      aduncum leaves were evaluated. Extract done by maceration method with ethanol has
      higher content of sesquiterpenes and antifungal activity. This extract may be
      useful as an alternative treatment for dermatophytosis. 

PMID- 24688524
TI  - Use of P450 cytochrome inhibitors in studies of enokipodin biosynthesis.
AB  - Enokipodins A, B, C, and D are antimicrobial sesquiterpenes isolated from the
      mycelial culture medium of Flammulina velutipes, an edible mushroom. The presence
      of a quaternary carbon stereocenter on the cyclopentane ring makes enokipodins A
      D attractive synthetic targets. In this study, nine different cytochrome P450
      inhibitors were used to trap the biosynthetic intermediates of highly oxygenated
      cuparene-type sesquiterpenes of F. velutipes. Of these, 1-aminobenzotriazole
      produced three less-highly oxygenated biosynthetic intermediates of enokipodins A
      D; these were identified as (S)-(-)-cuparene-1,4-quinone and epimers at C-3 of 6
      hydroxy-6-methyl-3-(1,2,2-trimethylcyclopentyl)-2-cyclohexen-1-one. One of the
      epimers was found to be a new compound. 

PMID- 24688525
TI  - Interaction of antimicrobial peptide Plantaricin149a and four analogs with lipid
      bilayers and bacterial membranes.
AB  - The amidated analog of Plantaricin149, an antimicrobial peptide from
      Lactobacillus plantarum NRIC 149, directly interacts with negatively charged
      liposomes and bacterial membranes, leading to their lysis. In this study, four
      Pln149-analogs were synthesized with different hydrophobic groups at their N
      terminus with the goal of evaluating the effect of the modifications at this
      region in the peptide's antimicrobial properties. The interaction of these
      peptides with membrane models, surface activity, their hemolytic effect on red
      blood cells, and antibacterial activity against microorganisms were evaluated.
      The analogs presented similar action of Plantaricin149a; three of them with no
      hemolytic effect (< 5%) until 0.5 mM, in addition to the induction of a helical
      element when binding to negative liposomes. The N-terminus difference between the
      analogs and Plantaricin149a retained the antibacterial effect on S. aureus and P.
      aeruginosa for all peptides (MIC50 of 19 MUM and 155 MUM to Plantaricin149a,
      respectively) but resulted in a different mechanism of action against the
      microorganisms, that was bactericidal for Plantaricin149a and bacteriostatic for
      the analogs. This difference was confirmed by a reduction in leakage action for
      the analogs. The lytic activity of Plantaricin149a is suggested to be a result of
      the peptide-lipid interactions from the amphipathic helix and the hydrophobic
      residues at the N-terminus of the antimicrobial peptide. 

PMID- 24688526
TI  - Extracellular proteases of Halobacillus blutaparonensis strain M9, a new
      moderately halophilic bacterium.
AB  - Halophilic microorganisms are source of potential hydrolytic enzymes to be used
      in industrial and/or biotechnological processes. In the present study, we have
      investigated the ability of the moderately halophilic bacterium Halobacillus
      blutaparonensis (strain M9), a novel species described by our group, to release
      proteolytic enzymes. This bacterial strain abundantly proliferated in Luria
      Bertani broth supplemented with 2.5% NaCl as well as secreted proteases to the
      extracellular environment. The production of proteases occurred in bacterial
      cells grown under different concentration of salt, ranging from 0.5% to 10% NaCl,
      in a similar way. The proteases secreted by H. blutaparonensis presented the
      following properties: (i) molecular masses ranging from 30 to 80 kDa, (ii) better
      hydrolytic activities under neutral-alkaline pH range, (iii) expression modulated
      according to the culture age, (iv) susceptibility to phenylmethylsulphonyl
      fluoride, classifying them as serine-type proteases, (v) specific cleavage over
      the chymotrypsin substrate, and (vi) enzymatic stability in the presence of salt
      (up to 20% NaCl) and organic solvents (e.g., ether, isooctane and cyclohexane).
      The proteases described herein are promising for industrial practices due to its
      haloalkaline properties. 

PMID- 24688527
TI  - An oxidant and organic solvent tolerant alkaline lipase by P. aeruginosa mutant:
      downstream processing and biochemical characterization.
AB  - An extracellular alkaline lipase from Pseudomonas aeruginosa mutant has been
      purified to homogeneity using acetone precipitation followed by anion exchange
      and gel filtration chromatography and resulted in 27-fold purification with 19.6%
      final recovery. SDS-PAGE study suggested that the purified lipase has an apparent
      molecular mass of 67 kDa. The optimum temperature and pH for the purified lipase
      were 45  degrees C and 8.0, respectively. The enzyme showed considerable
      stability in pH range of 7.0-11.0 and temperature range 35-55  degrees C. The
      metal ions Ca(2+), Mg(2+) and Na(+) tend to increase the enzyme activity,
      whereas, Fe(2+) and Mn(2+) ions resulted in discreet decrease in the activity.
      Divalent cations Ca(+2) and Mg(+2) seemed to protect the enzyme against thermal
      denaturation at high temperatures and in presence of Ca(+2) (5 mM) the optimum
      temperature shifted from 45  degrees C to 55  degrees C. The purified lipase
      displayed significant stability in the presence of several hydrophilic and
      hydrophobic organic solvents (25%, v/v) up to 168 h. The pure enzyme preparation
      exhibited significant stability and compatibility with oxidizing agents and
      commercial detergents as it retained 40-70% of its original activities. The
      values of K(m) and Vmax for p-nitrophenyl palmitate (p-NPP) under optimal
      conditions were determined to be 2.0 mg.mL(-1) and 5000 MUg.mL(-1).min(-1),
      respectively.

PMID- 24688528
TI  - Effect of alcohols on filamentation, growth, viability and biofilm development in
      Candida albicans.
AB  - In this study we report the potential of alcohols as morphogenetic regulators in
      Candida albicans. All the alcohols tested influenced various modes of growth like
      planktonic as well as biofilm forms. Viability was affected at high
      concentrations. Among the alcohols, the response of C. albicans to amyl alcohol
      (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not
      inhibitory to growth and viability specifically inhibited morphogenetic switching
      from yeast to hyphal forms. It also inhibited normal biofilm development favoring
      yeast dominated biofilms. Based on this study we hypothesize that alcohols
      produced under anaerobic conditions may not favor biofilm development and support
      dissemination of yeast cells. Since anaerobic conditions are not found to favor
      production of quorum sensing molecules like farnesol, the alcohols may play a
      role in morphogenetic regulation. 

PMID- 24688529
TI  - Microbiota and anthropic interference on antimicrobial resistance profile of
      bacteria isolated from Brazilian Maned-wolf (Chrysocyon brachyurus).
AB  - Both the study of Brazilian wild mammal fauna and the conditions that foster the
      preservation of endangered species, such as Brazilian Maned-wolf (Chrysocyon
      brachyurus), in wild life are of extreme importance. In order to study the
      resistance profile of microbiota bacterial colonizing Brazilian Maned-wolf, this
      work investigated samples from eight male captive and free roaming animals
      originating from different Brazilian geographical regions. Samples for
      microbiological purposes were collected with swabs and kept in appropriate
      transport medium. Using routine microbiological techniques, the isolated bacteria
      were tested toward antimicrobial drugs by the agar disk diffusion method. Results
      showed that all samples from wild animals were sensitive toward all drugs tested.
      Conversely, the resistance profile of bacteria isolated from captive animals
      varied among strains and animal body site location. Escherichia coli samples from
      prepuce, anus and ear showed multi-resistance toward at least four drugs,
      especially against erythromycin and tetracycline, followed by Proteus mirabilis
      and P. vulgaris strains isolated from anus and ear. Among Gram-positive bacteria,
      strains of coagulase-negative staphylococci showed multi-resistance mainly toward
      erythromycin and amoxicillin. The work discusses these findings and suggests that
      profile of multi-resistance bacteria from captive subjects may be attributed to
      direct contact with human or through lifestyle factors such as feeding, predation
      or contact of animals with urban animals such as birds, rodents, and insects from
      surrounding environments. 

PMID- 24688530
TI  - Prevalence of antibodies against Toxoplasma gondii and Neospora caninum in dogs.
AB  - Toxoplasmosis and neosporosis are parasitic diseases of global importance. The
      present study had the objective to determine the influence of age, sex and breed
      in the prevalence of antibodies against both diseases in dogs from Brotas city,
      Sao Paulo State, Brazil. Blood samples of 342 dogs were collected, and the age,
      sex and breed of each animal were recorded. The serological diagnosis for
      toxoplasmosis and neosporosis were performed using the immunofluorescent antibody
      test (IFAT). The Fischer's test was used to calculate the association probability
      of the variables, with alpha = 5%. For toxoplasmosis the prevalence of antibodies
      was 26.9% (CI 95% 22.4-31.8%), and for neosporosis 4.97% (CI 95% 3.1-7.8%). The
      statistical analysis revealed a higher risk of infection for T. gondii in dogs
      with more than five years. 

PMID- 24688531
TI  - Methylobacterium-plant interaction genes regulated by plant exudate and quorum
      sensing molecules.
AB  - Bacteria from the genus Methylobacterium interact symbiotically (endophytically
      and epiphytically) with different plant species. These interactions can promote
      plant growth or induce systemic resistance, increasing plant fitness. The plant
      colonization is guided by molecular communication between bacteria-bacteria and
      bacteria-plants, where the bacteria recognize specific exuded compounds by other
      bacteria (e.g. homoserine molecules) and/or by the plant roots (e.g. flavonoids,
      ethanol and methanol), respectively. In this context, the aim of this study was
      to evaluate the effect of quorum sensing molecules (N-acyl-homoserine lactones)
      and plant exudates (including ethanol) in the expression of a series of bacterial
      genes involved in Methylobacterium-plant interaction. The selected genes are
      related to bacterial metabolism (mxaF), adaptation to stressful environment
      (crtI, phoU and sss), to interactions with plant metabolism compounds (acdS) and
      pathogenicity (patatin and phoU). Under in vitro conditions, our results showed
      the differential expression of some important genes related to metabolism, stress
      and pathogenesis, thereby AHL molecules up-regulate all tested genes, except
      phoU, while plant exudates induce only mxaF gene expression. In the presence of
      plant exudates there is a lower bacterial density (due the endophytic and
      epiphytic colonization), which produce less AHL, leading to down regulation of
      genes when compared to the control. Therefore, bacterial density, more than plant
      exudate, influences the expression of genes related to plant-bacteria
      interaction. 

PMID- 24688532
TI  - Effectiveness of halo-tolerant, auxin producing Pseudomonas and Rhizobium strains
      to improve osmotic stress tolerance in mung bean (Vigna radiata L.).
AB  - Halo-tolerant, auxin producing bacteria could be used to induce salt tolerance in
      plants. A number of Rhizobium and auxin producing rhizobacterial strains were
      assessed for their ability to tolerate salt stress by conducting osmoadaptation
      assay. The selected strains were further screened for their ability to induce
      osmotic stress tolerance in mung bean seedlings under salt-stressed axenic
      conditions in growth pouch/jar trials. Three most effective strains of Rhizobium
      and Pseudomonas containing ACC-deaminase were evaluated in combination, for their
      ability to induce osmotic stress tolerance in mung bean at original, 4, and 6 dS
      m(-1) under axenic conditions. Results showed that sole inoculation of Rhizobium
      and Pseudomonas strains improved the total dry matter up to 1.4, and 1.9 fold,
      respectively, while the increase in salt tolerance index was improved up to 1.3
      and 2.0 fold by the Rhizobium and Pseudomonas strains, respectively. However, up
      to 2.2 fold increase in total dry matter and salt tolerance index was observed
      due to combined inoculation of Rhizobium and Pseudomonas strains. So, combined
      application of Rhizobium and Pseudomonas strains could be explored as an
      effective strategy to induce osmotic stress tolerance in mung bean. 

PMID- 24688533
TI  - Yearly variation of bacterial production in the Arraial do Cabo protection area
      (Cabo Frio upwelling region): an evidence of anthropogenic pressure.
AB  - Arraial do Cabo is where upwelling occurs more intensively on the Brazilian
      coast. Although it is a protection area it suffers anthropogenic pressure such as
      harbor activities and sporadic sewage emissions. Short-time studies showed a high
      variability of bacterial production (BP) in this region but none of them
      evaluated BP during long periods in a large spatial scale including stations
      under different natural (upwelling and cold fronts) and anthropogenic pressures.
      During 2006, we sampled surface waters 10 times (5 in upwelling and 5 in
      subsidence periods) in 8 stations and we measured BP, temperature as well as the
      concentrations of inorganic nutrients, pigments and particulate organic matter
      (POM). BP was up to 400 times higher when sewage emissions were observed visually
      and it had a positive correlation with ammonia concentrations. Therefore, in
      2007, we did two samples (each during upwelling and subsidence periods) during
      sewage emissions in five stations under different anthropogenic pressure and we
      also measured particles abundance by flow cytometry. The 12 samples in the most
      impacted area confirmed that BP was highest when ammonia was higher than 2 MUM,
      also reporting the highest concentrations of chlorophyll a and suspended
      particles. However, considering all measured variables, upwelling was the main
      disturbing factor but the pressure of fronts should not be neglected since it had
      consequences in the auto-heterotrophic coupling, increasing the concentrations of
      non fluorescent particles and POM. Stations clustered in function of natural and
      anthropogenic pressures degrees and both determined the temporal-spatial
      variability. 

PMID- 24688534
TI  - Gastric cancer in the young: is it a different clinical entity? A retrospective
      cohort study.
AB  - Background. The rate of gastric cancer in young patients has increased over the
      past few decades. The aim of this study was to search for independent risk
      factors related to patients of younger age. Methods. From January 1996 to
      December 2012, a series of 179 consecutive patients were admitted to our surgical
      department because of a gastric cancer. We carried out a retrospective cohort
      study in 20 patients younger than 50 and in 112 patients aged 50 and older
      treated by curative gastrectomy. The comparison involved the evaluation of
      patient and tumor characteristics. Results. Younger patients had significantly
      less comorbidities and a more favorable American Society of Anesthesiology score;
      they had significantly less preoperative weight loss and a significantly longer
      duration of symptoms; Helicobacter pylori infection and diffuse histological type
      were significantly associated with younger age. There was no statistically
      significant difference regarding overall and cancer-related 5-year survival;
      advanced cancer stage and diffuse histological type were the independent negative
      prognostic factors influencing cancer-related survival. Conclusions. We do not
      have sufficient evidence to consider gastric cancer in younger patients as a
      different clinical entity. Further studies are needed to understand
      carcinogenesis in younger patients and to improve gastric cancer classification. 

PMID- 24688535
TI  - Clinicopathological and immunohistochemical characterisation of gastric
      schwannomas in 29 cases.
AB  - Schwannomas are tumors arising from the nervous system that also occur
      infrequently in the gastrointestinal tract, most commonly in the stomach. This
      report characterizes 29 patients with benign or malignant gastric schwannomas.
      Surgical data and clinical follow-up information were available for 28 cases with
      a median postoperative duration of 57 months. Clinicopathological and
      immunohistochemical characteristics of benign and malignant schwannomas were
      analysed. Four cases (13.7%) were histologically diagnosed with malignant
      schwannoma. All tumors were positive for S-100 and CD56 proteins, displaying a
      diffuse staining pattern. Vimentin was expressed in 100% cases and all
      schwannomas were negative for smooth muscle actin, c-kit, and HMB-45. A
      significant difference was observed between the group of benign and malignant
      schwannomas as regards recurrences and metastasis after complete resection (P =
      0.015). The survival time of patients with benign schwannomas was longer than the
      malignant group (P = 0.013), so gastric malignant schwannomas have a potential
      for recurrence and metastasis, with subsequently short survival. Complete
      resection with an attempt to remove all tumor tissue with negative margins is of
      paramount importance in the management of gastric schwannomas, particularly when
      they turn out to be malignant. 

PMID- 24688536
TI  - Extended salvage pelvic lymph node dissection in patients with recurrent prostate
      cancer.
AB  - Background. Treatment of patients with a biochemical recurrence (BCR) of prostate
      cancer (PCa) is generally difficult and without valid treatment options. Since
      2004 we have been developing therapeutic possibilities for these patients.
      Methods. We retrospectively analyzed a cohort of 41 patients with a BCR of PCa
      and a mean followup of 40.3 +/- 20.8 months. Group 1 (n = 10): salvage radical
      prostatectomy (sRP) with SePLND (salvage extended pelvic lymph nodes dissection)
      (initial treatment: combined brachytherapy). Group 2 (n = 22): SePLND (initial
      treatment: radical prostatectomy (RP)). Group 3 (n = 9): SePLND (initial
      treatment: RP and adjuvant radiation therapy (RT)). We observed PSA, PSA
      velocity, localization of LNs and LNs+, BCR-free period, and BR (biochemical
      response). Results. Group 1: 60% with BCR-freedom (mean 27.2 months). Group 2:
      63.6% with BCR-freedom (mean 17.5 months). Group 3: 33.3% with BCR-freedom (mean
      17.6 months). In total, BCR-freedom was observed in 23 of 41 patients (56.1%)
      after salvage surgery. 75.6% of all patients showed a BR. 765 LNs were removed
      and 14.8% of these were LN+. Conclusions. The BCR-free period and BR are
      comparable in all three groups. Sensibility to ADT can be reestablished and
      prolonged as a result of SePLND. Multicenter studies are needed for a reliable
      output. 

PMID- 24688537
TI  - Learning curves of macintosh laryngoscope in nurse anesthetist trainees using
      cumulative sum method.
AB  - Background. Tracheal intubation is a potentially life-saving procedure. This
      skill is taught to many anesthetic healthcare professionals, including nurse
      anesthetists. Our goal was to evaluate the learning ability of nurse anesthetist
      trainees in their performance of orotracheal intubation with the Macintosh
      laryngoscope. Methods. Eleven nurse anesthetist trainees were enrolled in the
      study during the first three months of their training. All trainees attended
      formal lectures and practice sessions with manikins at least one time on
      performing successful tracheal intubation under supervision of anesthesiology
      staff. Learning curves for each nurse anesthetist trainee were constructed with
      the standard cumulative summation (cusum) methods. Results. Tracheal intubation
      was attempted on 388 patients. Three hundred and six patients (78.9%) were
      successfully intubated on the trainees' first attempt and 17 patients (4.4%) on
      the second attempt. The mean +/- SD number of orotracheal intubations per trainee
      was 35.5 +/- 5.1 (range 30-47). Ten (90.9%) of 11 trainees crossed the 20%
      acceptable failure rate line. A median of 22 procedures was required to achieve
      an 80% orotracheal intubations success rate. Conclusion. At least 22 procedures
      were required to reach an 80% success rate for orotracheal intubation using
      Macintosh laryngoscope in nonexperienced nurse anesthetist trainees. 

PMID- 24688538
TI  - Botulinum toxin suppression of CNS network activity in vitro.
AB  - The botulinum toxins are potent agents which disrupt synaptic transmission. While
      the standard method for BoNT detection and quantification is based on the mouse
      lethality assay, we have examined whether alterations in cultured neuronal
      network activity can be used to detect the functional effects of BoNT. Murine
      spinal cord and frontal cortex networks cultured on substrate integrated
      microelectrode arrays allowed monitoring of spontaneous spike and burst activity
      with exposure to BoNT serotype A (BoNT-A). Exposure to BoNT-A inhibited spike
      activity in cultured neuronal networks where, after a delay due to toxin
      internalization, the rate of activity loss depended on toxin concentration. Over
      a 30 hr exposure to BoNT-A, the minimum concentration detected was 2 ng/mL, a
      level consistent with mouse lethality studies. A small proportion of spinal cord
      networks, but not frontal cortex networks, showed a transient increase in spike
      and burst activity with exposure to BoNT-A, an effect likely due to preferential
      inhibition of inhibitory synapses expressed in this tissue. Lastly, prior
      exposure to human-derived antisera containing neutralizing antibodies prevented
      BoNT-A induced inhibition of network spike activity. These observations suggest
      that the extracellular recording from cultured neuronal networks can be used to
      detect and quantify functional BoNT effects. 

PMID- 24688540
TI  - Benign Aspirates on Follow-Up FNA May Be Enough in Patients with Initial Atypia
      of Undetermined Significance/Follicular Lesion of Undetermined Significance.
AB  - Background. Management of thyroid nodules with benign aspirates following atypia
      of undetermined significance/follicular lesion of undetermined significance
      (AUS/FLUS) is not well established. We reviewed the risk of malignancy and the
      role of ultrasound (US) features among thyroid nodules with benign results
      following initial AUS/FLUS diagnoses. Methods. From December 2009 to February
      2011, a total of 114 nodules in 114 patients diagnosed as benign on follow-up
      fine-needle aspiration (FNA) after AUS/FLUS results were included in our study.
      Eight among 114 nodules were confirmed pathologically and 106 were clinically
      observed by a follow-up FNA or US. Suspicious US features were defined as
      markedly hypoechogenicity, irregular or microlobulated margin, presence of
      microcalcifications, and taller than wide shape. Results. There were 110 (96.5%)
      benign nodules and 4 (3.5%) malignant nodules. Two (4.8%) among 42 nodules
      without suspicious US features and 2 (2.8%) out of 72 nodules with suspicious US
      features were confirmed as malignancy, but there were no significant associations
      between the malignancy rate and US features (P = 0.625). Conclusion. Clinical
      follow-up instead of surgical excision or continuous repeat FNA may be enough for
      benign thyroid nodules after AUS/FLUS. The role of US features might be
      insignificant in the management of these nodules. 

PMID- 24688539
TI  - Benign prostatic hyperplasia: a new metabolic disease of the aging male and its
      correlation with sexual dysfunctions.
AB  - Metabolic syndrome (MetS) is a well-recognized cluster of cardiovascular (CV)
      risk factors including obesity, hypertension, dyslipidemia, and hyperglycaemia,
      closely associated with an increased risk of forthcoming cardiovascular disease
      and type 2 diabetes mellitus. Emerging evidence indicates that benign prostate
      hyperplasia (BPH) and its related lower urinary tract symptoms (LUTS) represent
      other clinical conditions frequently observed in subjects with MetS. Several
      modifiable factors involved in MetS determinism, such as inadequate diet, lack of
      physical exercise, and smoking and drinking behaviours are emerging as main
      contributors to the development of BPH. The pathogenetic mechanisms underlying
      the connection between MetS and BPH have not been completely clarified. MetS and
      its components, hypogonadism, and prostate inflammation probably play an
      important role in inducing BPH/LUTS. Although historically considered as a
      "normal" consequence of the aging process, BPH/LUTS should now be faced
      proactively, as a preventable disorder of the elderly. Type of diet and level of
      physical activity are now considered important factors affecting prostate health
      in the aging male. However, whether physical exercise, weight loss, and
      modifications of dietary habit can really alter the natural history of BPH/LUTS
      remains to be determined. Further research is advisable to better clarify these
      points. 

PMID- 24688541
TI  - Progressive Improvement of T-Scores in Men with Osteoporosis and Subnormal Serum
      Testosterone Levels upon Treatment with Testosterone over Six Years.
AB  - Testosterone deficiency leads to bone loss and testosterone treatment has a
      beneficial effect. This study investigated the effects of normalizing serum
      testosterone on bone mineral density in 45 men with osteoporosis, diagnosed with
      testosterone deficiency (serum testosterone levels <12.1 nmol/L, T-scores: (mean
      +/- SD) -3.12 +/- 0.45, minimum: -4.10, and maximum: -2.60). In a cumulative,
      prospective, registry study of hypogonadal men (mean age: 53 +/- 7 years) they
      received parenteral testosterone undecanoate of 1000 mg/12 weeks for up to six
      years. After one year 44 men were included in the registry, after two years 36
      men, after three years 32 men, after four years 25 men, after five years 10 men
      and after six years 4 men. The declining numbers do not reflect drop-out rates
      but are a result of the registry design. Over the 6 year period there was a
      significant and progressive improvement of the T-scores in these men. Normalizing
      of serum testosterone leads to an improvement of bone mineral density and this
      improvement was progressive with the time period of testosterone administration.
      In this study of 6-years many men with testosterone deficiency suffered from
      classical diagnoses (Klinefelter's syndrome and testicular pathology) hitherto
      undiagnosed. 

PMID- 24688542
TI  - Effects of five-year treatment with testosterone undecanoate on metabolic and
      hormonal parameters in ageing men with metabolic syndrome.
AB  - Metabolic and hormonal modifications after long-term testosterone (T) treatment
      have never been investigated. 20 hypogonadal men (mean T = 241 ng/dL-8.3 nmol/L)
      with metabolic syndrome (MS, mean age 58) were treated with T-undecanoate
      injections every 12 weeks for 60 months. 20 matched subjects in whom T was
      unaccepted or contraindicated served as controls. Primary endpoints were
      variations from baseline of metabolic and hormonal parameters. In T-group,
      significant reductions in waist circumference (-9.6 +/- 3.8 cm, P < 0.0001), body
      weight (-15 +/- 2.8 Kg, P < 0.0001), and glycosylated hemoglobin (-1.6  +/- 
      0.5%, P < 0.0001) occurred, along with improvements in insulin sensitivity (HOMA
      I; -2.8  +/-  0.6, P < 0.0001), lipid profile (total/HDL-cholesterol ratio -2.9
      +/- 1.5, P < 0.0001), systolic and diastolic blood pressure (-23 +/- 10 and -16
      +/- 8 mm Hg, P < 0.0001, resp.), and neck and lumbar T-scores (+0.5 +/- 0.15
      gr/cm(2), P < 0.0001; +0.7 +/- 0.8, P < 0.0001, resp.). Also, serum vitamin D
      (+14.0 +/- 1.3 ng/mL, P < 0.01), TSH (- 0.9 +/- 0.3 mUI/mL, P < 0.01), GH (0.74
      +/- 0.2 ng/mL, P < 0.0001), and IGF1 (105 +/- 11 ng/mL, P < 0.01) levels changed
      in T-group but not in controls. Normalization of T levels in men with MS improved
      obesity, glycemic control, blood pressure, lipid profile, and bone mineral
      density compared with controls. Amelioration in hormonal parameters, that is,
      vitamin D, growth hormone, and thyrotropin plasma levels, were reported. 

PMID- 24688543
TI  - Association between Related Purine Metabolites and Diabetic Retinopathy in Type 2
      Diabetic Patients.
AB  - Aims. The purpose of the study was to investigate the differences of adenosine,
      adenine, inosine, xanthine, hypoxanthine, and uric acid concentrations in
      patients with type 2 diabetes mellitus and diabetic retinopathy and assess the
      relationship between purine metabolites and disease. Materials and Methods. The
      study group consisted of 114 subjects which were divided into three groups:
      control (n = 40), type 2 diabetes without retinopathy (n = 35), and type 2
      diabetes with retinopathy (n = 39). Levels of metabolites were measured in plasma
      of all participants. Results. There is a significant increase of levels of
      adenosine (0.94 +/- 0.17 mg/L versus 0.17 +/- 0.01 mg/L, P < 0.001), inosine
      (0.297 +/- 0.078 mg/L versus 0.086 +/- 0.010 mg/L, P < 0.001), xanthine (1.01 +/-
      0.21 mg/L versus 0.54 +/- 0.05 mg/L, P = 0.009), and uric acid (70.55 +/- 3.97
      mg/L versus 53.81 +/- 2.36 mg/L, P < 0.001) with diabetic retinopathy compared to
      diabetes mellitus. The levels of adenine, hypoxanthine, and xanthine oxidase did
      not change. Uric acid, xanthine, inosine, and adenosine correlated positively
      with systolic blood pressure and urea nitrogen. Conclusions. The levels of
      adenosine, inosine, uric acid, and xanthine may be useful for monitoring the
      progression of diabetic retinopathy and evaluating the treatment. 

PMID- 24688544
TI  - Application of technology in endocrine disease.

PMID- 24688545
TI  - The linker histone h1.2 is an intermediate in the apoptotic response to cytokine
      deprivation in T-effectors.
AB  - Tissue homeostasis is a dynamic process involving proliferation and the removal
      of redundant or damaged cells. This is exemplified in the coordinated deletion
      triggered by limiting trophic factors/cytokines in the extracellular milieu-of
      differentiated T cells overproduced during the mammalian immune response.
      However, mechanisms by which extracellular cues are perceived and transduced as
      apoptotic triggers remain incompletely understood. T-effectors are dependent on
      cytokines for survival and undergo apoptosis following cytokine withdrawal. Here
      we report that leptomycin B (LMB), an inhibitor of nuclear export machinery,
      protected T-effectors from apoptosis implicating a nuclear intermediate in the
      apoptotic pathway. Evidence is presented that the linker histone H1.2 localizes
      to the cytoplasm, by a mechanism sensitive to regulation by LMB, to activate
      apoptotic signaling culminating in nuclear and mitochondrial damage in T
      effectors in response to cytokine deprivation. H1.2 is detected in a complex with
      the proapoptotic mitochondrial resident Bak and its subcellular localization
      regulated by Jun-N-terminal kinase (JNK), an intermediate in the apoptotic
      cascade in T-effectors. These data suggest that metabolic stressors may impinge
      on H1.2 dynamics favoring its activity at the mitochondrion, thereby functioning
      as a molecular switch for T-effector apoptosis. 

PMID- 24688546
TI  - Mitochondrial DNA and functional investigations into the radiosensitivity of four
      mouse strains.
AB  - We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA
      ratios are significant to mitochondrial function and if a material effect on
      mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6
      (radioresistant), and F1 hybrid mouse strains were exposed to total body
      irradiation. Hepatic genomic DNA was extracted, and mitochondria were isolated.
      Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling
      were measured. Radiation influenced strain-specific survival in vivo. F1 hybrid
      survival was influenced by maternal input. Changes in mitochondrial content
      corresponded to survival in vivo among the 4 strains. Calcium-induced
      mitochondrial swelling was strain dependent. Isolated mitochondria from BALB/c
      mice were significantly more sensitive to calcium overload than mitochondria from
      C57BL/6 mice. Maternal input partially influenced the recovery effect of
      radiation on calcium-induced mitochondrial swelling in F1 hybrids; the hybrid
      with a radiosensitive maternal lineage exhibited a lower rate of recovery.
      Hybrids had a survival rate that was biased toward maternal input. mtDNA content
      and mitochondrial permeability transition pores (MPTP) measured in these strains
      before irradiation reflected a dominant input from the parent. After irradiation,
      the MPTP opened sooner in radiosensitive and hybrid strains, likely triggering
      intrinsic apoptotic pathways. These findings have important implications for
      translation into predictors of radiation sensitivity/resistance. 

PMID- 24688547
TI  - Occurrence of Bordetella infection in pigs in northern India.
AB  - Bordetella bronchiseptica infection causing atrophic rhinitis in pigs is reported
      from almost all countries. In the present study, occurrence of Bordetella
      infection in apparently healthy pigs was determined in 392 pigs sampled to
      collect 358 serum samples and 316 nasal swabs from Northern India by conventional
      bacterioscopy, detection of antigen with multiplex polymerase chain reaction
      (mPCR), and detection of antibodies with microagglutination test (MAT) and enzyme
      linked immune-sorbent assay (ELISA). Bordetella bronchiseptica could be isolated
      from six (1.92%) nasal swabs. Although isolates varied significantly in their
      antimicrobial sensitivity, they had similar plasmid profile. The genus specific
      and species specific amplicons were detected from 8.2% and 4.4% nasal swabs using
      mPCR with alc gene (genus specific) and fla gene and fim2 gene (species specific)
      primers, respectively. Observations revealed that there may be other bordetellae
      infecting pigs because about 50% of the samples positive using mPCR for genus
      specific amplicons failed to confirm presence of B. bronchiseptica. Of the pig
      sera tested with MAT and ELISA for Bordetella antibodies, 67.6% and 86.3%
      samples, respectively, were positive. For antigen detection mPCR was more
      sensitive than conventional bacterioscopy while for detection of antibodies
      neither of the two tests (MAT and ELISA) had specificity in relation to antigen
      detection. Study indicated high prevalence of infection in swine herds in
      Northern India. 

PMID- 24688548
TI  - Hearing benefit in allograft tympanoplasty using tutoplast processed malleus.
AB  - Objectives. Tutoplast processed human cadaveric ossicular allografts are a safe
      alternative for ossicular reconstruction where there is insufficient material
      suitable for autograft ossiculoplasty. We present a series of 7 consecutive cases
      showing excellent air-bone gap closure following canal-wall-down mastoidectomy
      for cholesteatoma and reconstruction of the middle ear using Tutoplast processed
      malleus. Patients and Methods. Tympanoplasty with Tutoplast processed malleus was
      performed in seven patients to reconstruct the middle ear following canal-wall
      down mastoidectomy in a tertiary ENT centre. Main Outcome Measures. Hearing
      improvement and recurrence-free period were assessed. Pre-and postoperative
      audiograms were performed. Results. The average pre operative hearing loss was 50
      +/- 13 dB, with an air-bone gap of 33 +/- 7 dB. Post operative audiograms at 25
      months demonstrated hearing thresholds of 29 +/- 10 dB, with an air-bone gap of
      14 +/- 6 dB. No prosthesis extrusion was observed, which compares favourably to
      other commercially available prostheses. Conclusions. Tutoplast processed
      allografts restore conductive hearing loss in patients undergoing mastoidectomy
      and provide an excellent alternative when there is insufficient material suitable
      for autograft ossiculoplasty. 

PMID- 24688550
TI  - Prevalence of Dental Caries in relation to Body Mass Index, Daily Sugar Intake,
      and Oral Hygiene Status in 12-Year-Old School Children in Mathura City: A Pilot
      Study.
AB  - Aim. To correlate the prevalence of dental caries to body mass index, daily sugar
      intake, and oral hygiene status of 12-year-old school children of Mathura city.
      Material and Methods. The study design was cross-sectional and included 100
      school children aged 12 years (n = 50 boys and n = 50 girls) who were randomly
      selected from two schools based upon inclusion and exclusion criteria. Body
      weight/height was recorded and BMI was calculated and plotted on CDC-BMI for age
      growth charts/curves for boys and girls to obtain percentile ranking. Dental
      caries was recorded using WHO criteria. Oral hygiene status of the study subjects
      was assessed using oral hygiene index-simplified. Data regarding the daily sugar
      intake was recorded using 24-hour recall diet frequency chart. The data obtained
      was analysed using SPSS version 11.5 for windows. Result. Only 27 subjects were
      affected by caries. The mean DMFT/dmft was 0.37 +/- 0.79 and 0.12 +/- 0.60,
      respectively. Statistical analysis by means of a logistic regression model
      revealed that only oral hygiene status had a significant effect on caries
      prevalence (OR = 5.061, P = 0.004), whereas daily sugar intake and body mass
      index had no significant effect. Conclusion. From the analysis, it was concluded
      that oral hygiene status had a significant effect on caries prevalence of 12-year
      old school children of Mathura city. 

PMID- 24688549
TI  - Current Neonatal Resuscitation Practices among Paediatricians in Gujarat, India.
AB  - Aim. We assessed neonatal resuscitation practices among paediatricians in
      Gujarat. Methods. Cross-sectional survey of 23 questions based on guidelines of
      Neonatal Resuscitation Program (NRP) and Navjaat Shishu Suraksha Karyakram (NSSK)
      was conducted using web-based tool. Questionnaire was developed and consensually
      validated by three neonatologists. Results. Total of 142 (21.2%) of 669
      paediatricians of Gujarat, India, whose e-mail addresses were available,
      attempted the survey and, from them, 126 were eligible. Of these, 74 (58.7%) were
      trained in neonatal resuscitation. Neonatal Intensive Care Unit with mechanical
      ventilation facilities was available for 54% of respondents. Eighty-eight (69.8%)
      reported correct knowledge and practice regarding effective bag and mask
      ventilation (BMV) and chest compressions. Knowledge and practice about continuous
      positive airway pressure use in delivery room were reported in 18.3% and 30.2%
      reported use of room air for BMV during resuscitation. Suctioning oral cavity
      before delivery in meconium stained liquor was reported by 27.8% and 38.1% cut
      the cord after a minute of birth. Paediatricians with NRP training used
      appropriate method of tracheal suction in cases of nonvigorous newborns than
      those who were not trained. Conclusions. Contemporary knowledge about neonatal
      resuscitative practices in paediatricians is lacking and requires improvement.
      Web-based tools provided low response in this survey. 

PMID- 24688551
TI  - Recombinant human trefoil factor 3 ameliorates bowel injury: its anti
      inflammatory effect on experimental necrotizing enterocolitis.
AB  - Aim. Recombinant human trefoil factor 3 (intestinal trefoil factor) has been
      suggested to be partially protective against necrotizing enterocolitis (NEC), but
      the mechanisms of this protection have not been defined. We investigated whether
      the protective effects of rhTFF3 are the result of an anti-inflammatory response.
      Methods. The rats were killed on day 4, the distal ileum was harvested for
      morphological studies and immunohistochemistry for NF- kappa B (p65), and the
      amounts of IL-1 beta , IL-6, and IL-10 in the intestinal tissue were measured
      using commercial ELISA assay kits. Results. In the neonatal NEC, IL-1 beta , IL
      6, and IL-10 were significantly higher than in normal group. In normal group, IL
      1 beta and IL-6 were significantly decreased, and the amount of IL-10 was
      markedly increased compared with NEC group. In the NEC model, immunohistochemical
      staining for NF- kappa B (p65) was demonstrated to be of a strong brown color and
      was distributed in the intestinal epithelium. Treatment with rhTFF3 significantly
      decreased the immunoreactivity of NF- kappa B (p65) in the NEC model.
      Conclusions. Intestinal inflammation was ameliorated after rhTFF3 was injected.
      rhTFF3 may protect against the intestinal injury of the neonatal rat NEC model by
      suppression of the inflammatory response. 

PMID- 24688552
TI  - Comprehensive planning for classification and disposal of solid waste at the
      industrial parks regarding health and environmental impacts.
AB  - The aim of this study is the comprehensive planning for integrated management of
      solid waste at the industrial parks. The share of each industrial group including
      food, metal, chemical, non-metallic minerals, textile, electrical and
      electronical, and cellulose industries were 48.2, 14.9, 6.7, 22, 0.9, 0.6, and
      6.5 percent, respectively. The results showed that nearly half of total
      industrial waste produced from the range of biological materials are
      biodegradable and discharging them without observing environmental regulations
      leads to short-term pollution and nuisance in the acceptor environment. Also some
      parts of case study waste were recyclable which is considerable from viewpoint of
      economical and environmental pollution. Long-term impacts will appear due to
      improper site selection of disposal from the spatial standpoint. In this way, an
      approach for site selection using several socioeconomic, physical, and
      environmental criteria based on multicriteria decision making model (MCDM) is
      introduced. Health risks and environment pollution such as soil and surface water
      may be done. It is essential to revise the studied industries layout,
      particularly those units which produce special waste which should be more
      cautious. Also stricter enforcement is required as an effective step in reducing
      the harmful impacts of it. 

PMID- 24688553
TI  - The association of periodontitis and metabolic syndrome.
AB  - Metabolic syndrome (MS) is a condition, which constitutes a group of risk factors
      that occur together and increase the risk for Coronary Artery Disease, Stroke and
      type 2 diabetes mellitus. This disorder is found prevalent in the industrialized
      societies of the world in epidemic proportions. Periodontitis is an oral disease
      of microbial origin characterized by loss of attachment apparatus of tooth,
      resulting in edentulism if untreated. Periodontitis has been attributed to
      produce a low grade systemic inflammatory condition. The link of periodontitis to
      various systemic disorders has led to the evolution of a new branch termed as
      "periodontal medicine." Studies reviewed in the present paper have indicated a
      positive link between the MS and periodontitis and it is suggested that subjects
      displaying several components of MS should be submitted to periodontal
      examination. Present studies have displayed coherent relation between the two
      entities. This review will address the vicious association between MS and
      periodontitis, depicting the commonality of pathophysiological pathway between
      the two entities. Systematic reviews, meta-analysis addressing the concerned
      subject were screened. Whether the systematic periodontal therapy in individuals
      exhibiting MS has the potential to reduce the incidence of various adverse
      systemic complications remains a logical proposition. Further, longitudinal and
      controlled trials with a large population would be imperative to depict the
      robustness in the association between MS and periodontal disease in human
      subjects. 

PMID- 24688554
TI  - Salivaomics - A promising future in early diagnosis of dental diseases.
AB  - Human saliva plays an important role in the health of the oral cavity and of the
      body as a whole. Salivary diagnostics is a dynamic and emerging field in the
      diagnosis of oral and systemic diseases. Saliva reflects the physiologic state of
      the body, including emotional, endocrinal, nutritional, and metabolic variations.
      The collection of saliva samples is noninvasive, safe, and inexpensive.
      Traditional clinical criteria are insufficient for determining sites of active
      disease, for monitoring the response to therapy, or for measuring the degree of
      susceptibility to future disease progression. Salivaomics includes five
      diagnostic alphabets proteins, mRNAs, miRNAs, metabolic compounds, and microbes
      offering substantial advantages because disease states may be accompanied by
      detectable changes. Salivaomics, the future of saliva-based techniques for early
      diagnosis of dental diseases, is promising and may offer a robust alternative for
      clinicians to use in the near future to make clinical decisions. 

PMID- 24688555
TI  - The biology of distraction osteogenesis for correction of mandibular and
      craniomaxillofacial defects: A review.
AB  - Limb lengthening by distraction osteogenesis was first described in 1905. The
      technique did not gain wide acceptance until Gavril Ilizarov identified the
      physiologic and mechanical factors governing successful regeneration of bone
      formation. Distraction osteogenesis is a new variation of more traditional
      orthognathic surgical procedure for the correction of dentofacial deformities. It
      is most commonly used for the correction of more severe deformities and syndromes
      of both the maxilla and the mandible and can also be used in children at ages
      previously untreatable. The basic technique includes surgical fracture of
      deformed bone, insertion of device, 5-7 days rest, and gradual separation of bony
      segments by subsequent activation at the rate of 1 mm per day, followed by an 8
      12 weeks consolidation phase. This allows surgeons, the lengthening and reshaping
      of deformed bone. The aim of this paper is to review the principle, technical
      considerations, applications and limitations of distraction osteogenesis. The
      application of osteodistraction offers novel solutions for surgical-orthodontic
      management of developmental anomalies of the craniofacial skeleton as bone may be
      molded into different shapes along with the soft tissue component gradually
      thereby resulting in less relapse. 

PMID- 24688556
TI  - Effect of image compression of direct digital lateral cephalograms on the
      identification of cephalometric points.
AB  - BACKGROUND: With increase of digital imaging, the need for storage space and
      transmission speed also increases. Compressed images need less storage space and
      decrease the transmission time. However, compression could compromise image
      quality. The aim of this study was to evaluate the influence of image compression
      on the identification of cephalometric points on direct digital lateral
      cephalogram images, compared with the digital imaging and communications in
      medicine (DICOM) format. MATERIALS AND METHODS: In this analytical-descriptive
      study, 19 direct digital lateral cephalograms saved in DICOM format were used.
      They were converted to joint photographic experts group (JPEG) 2000 format with
      quality factors 85, 75, and 60 adding up to 76 images (DICOM, JPEG 85, 75, and
      60). The images were randomized and eight cephalometric points were identified on
      each image by a professional, using the x-y coordinate system. Analysis of
      variance (ANOVA) was applied to investigate if there was a statistically
      significant difference in the location of cephalometric points between each group
      of images. All tests were applied at a significance level of 5%. RESULTS: The
      results did not demonstrate any statistically significant difference in the
      identification of the eight cephalometric points between the DICOM images and the
      JPEG2000 quality factors 85, 75, and 60. CONCLUSION: JPEG2000 images of lateral
      cephalograms with quality factors 85, 75, and 60 did not demonstrate any
      alterations in the identification of cephalometric points compared with the DICOM
      format. JPEG2000 is a reliable file format for the compression of digital lateral
      cephalograms.

PMID- 24688557
TI  - Effect of polymerization mode of two adhesive systems on push-out bond strength
      of fiber post to different regions of root canal dentin.
AB  - BACKGROUND: A few studies have investigated the effect of the activation mode of
      adhesive systems on bond strength of fiber posts to root canal dentin. This study
      investigated the push-out bond strengths of a glass fiber post to different root
      canal regions with the use of two adhesives with light- and dual-cure
      polymerization modes. MATERIALS AND METHODS: In this in vitro study, 40 maxillary
      central incisors were decoronated at cement-enamel junction with 15 +/- 1 mm root
      length. After root canal therapy and post space preparations, they were randomly
      divided into four groups. Post spaces were treated with four different adhesives:
      Excite, Excite Dual cure Single Component (DSC), self-etch adhesive (AdheSE), and
      AdheSE dual-cure. Then the fiber-reinforced composite (FRC) post, Postec Plus,
      was cemented with dual-cure resin cement, Variolink II. The roots were cut into
      three 2-mm-thick slices. Push-out tests were performed with a universal testing
      machine at a crosshead speed of 0.5 mm/min. The mode of failures was determined
      under a stereomicroscope. Data were analyzed by three-way analysis of variance
      (ANOVA) and Tukey test was conducted to compare post hoc with P < 0.05 as the
      level of significance. RESULTS: The highest bond strength was obtained for AdheSE
      dual-cure (15.54 +/- 6.90 MPa) and the lowest was obtained for Excite light-cure
      (10.07 +/- 7.45 MPa) and only the bond strength between these two adhesives had
      significant difference (P = 0.02). Bond strength decreased from the coronal to
      the apical in all groups and this was significant in Excite (group 1) and AdheSE
      (group 3) (P < 0.001). In apical regions, bond strength of dual-cure adhesives
      was significantly higher than light-cure adhesives (P < 0.001). CONCLUSION: Push
      out bond strength of fiber post to different regions of root canal dentin was
      affected by both adhesive systems and their polymerization modes.

PMID- 24688558
TI  - Comparing the range of MU and beta angles in 6-17-year-old children of Isfahan
      with normal occlusion.
AB  - BACKGROUND: Linear and angular measurements such as A point, nasion, B point
      (ANB) angle and Wits appraisal index are not accurate enough to evaluate sagittal
      relationship of the jaws. The aim of this study was to evaluate and compare the
      range of MU and beta angles in 6-17-year-old children of Isfahan, having normal
      occlusion. MATERIALS AND METHODS: This was an analytical descriptive study. For
      this study, 235 cephalometric radiographs of patients who didn't receive
      orthodontics treatments and based on 13 indexes had normal occlusion, were
      selected. After tracing of cephalograms, ANB angle, Wits appraisal index, MU
      angle (resulted from the intersection of AB line and perpendicular line from
      point A to mandibular plane) and beta angle (resulted from the intersection of AB
      line and perpendicular line from point A on CB line) were measured. Data was
      analyzed by t-test, ANOVA and Pierson-Spearman correlation coefficient (P <
      0.05). RESULTS: Mean value of MU and beta angles were 17.34 +/- 3.47 and 31.7 +/-
      3.31 and ranged from 8-27 to 21.5-39 respectively. According to t-test, there was
      a significant difference between two sex groups for MU angle (P = 0.02); however,
      it was not significant for beta angle. According to Spearman correlation
      coefficient, there was no significant difference between age and MU angle;
      however, beta angle was directly and significantly related to age (r = 0.435).
      There was significant and reverse relationship between MU and beta angles with
      ANB angle and Wits appraisal index. CONCLUSION: MU and beta angles are reliable
      and can be used to evaluate the anterior-posterior relationship of the jaws.

PMID- 24688559
TI  - Prevalence of talon cusps in a Portuguese population: Forensic identification
      significance of a rare trait.
AB  - BACKGROUND: Dental techniques are frequently used in human identification; some
      of those include comparative analyses of dental features that, being rare or
      unique to an individual, can establish a positive identification. The usefulness
      of each feature depends on its population, frequency, and uniqueness. The aim of
      this study was to determine the prevalence of talon cusps in a Portuguese
      population. MATERIALS AND METHODS: A prospective study was performed. Three
      hundred and two patients were studied, and talon cusps presence was assessed.
      Statistical tests were carried out using Statistical Package for the Social
      Sciences (SPSS) 17 software (SPSS Inc., Chicago, IL, USA). Statistical analysis
      relied primarily on descriptive statistics and crosstabs, with Chi-square
      analysis. RESULTS: Results showed that talon cusps were observed in only 6.3% of
      patients. The maxillary lateral incisors were the most common teeth showing this
      feature (82.1% of all teeth). CONCLUSION: It can be concluded that talon cusps
      are an uncommon trait in these Portuguese population, and therefore, it is a
      feature that can be potentially very useful in forensic human identification,
      when antemortem dental records are available.

PMID- 24688560
TI  - Effect of bracket bonding with Er: YAG laser on nanomechanical properties of
      enamel.
AB  - BACKGROUND: The aim of this study was to compare the effects of conventional acid
      etching and laser etching on the nano-mechanical properties of the dental enamel
      using nano-indentation test. MATERIALS AND METHODS: In this experimental in vitro
      study, buccal surfaces of 10 premolars were divided into three regions. One of
      the regions was etched with 37% phosphoric acid and another etched with Er:YAG
      laser, the third region was not etched. The brackets were bonded to both of
      etched regions. After thermocycling for 500 cycles, the brackets were removed and
      the teeth were decoronated from the bracket bonding area. Seven nano-indentations
      were applied at 1-31 MUm depth from the enamel surface in each region. Mean
      values of the hardness and elastic modulus were analyzed with repeated measures
      analysis of variance and Tukey HSD tests, using the SPSS software (SPSS Inc.,
      version16.0, Chicago, Il, USA). P < 0.05 was considered as significant. RESULTS:
      The hardness up to 21 MUm in depth and elastic modulus up to 6 MUm in depth from
      the enamel surface for laser-etched enamel had significantly higher values than
      control enamel and the hardness up to 11 MUm in depth and elastic modulus up to 6
      MUm in depth for acid-etched enamel had significantly lower values than the
      control enamel. CONCLUSION: The mechanical properties of the enamel were
      decreased after bracket bonding with conventional acid etching and increased
      after bonding with Er:YAG laser.

PMID- 24688561
TI  - A comparative evaluation of working length with digital radiography and third
      generation apex locator (ProPex) in the presence of various intracanal irrigants:
      An in vivo/ex vivo study.
AB  - BACKGROUND: Accurate working length determination is a pre-requisite for a
      successful endodontic treatment. Even with improved systems of working length
      measurement, different readings may be recorded in different electrolytes present
      in the canal. The purpose of this in vivo/ex vivo comparative study was to
      determine the accuracy in measuring the working length of root canal using Direct
      Digital Radiographic Method (Radiovisiography or RVG) and ProPex electronic apex
      locator in the presence of three different irrigating solutions: 0.9% normal
      saline, 2% chlorhexidine, 3% NaOCl solutions. MATERIALS AND METHODS: Forty single
      rooted human teeth scheduled for extraction with mature apices were selected for
      this study. Measurements were performed by using RVG and ProPex in the presence
      of irrigating solutions. After extraction of the teeth, light microscope was used
      to confirm visually the relationship of the tip of the endodontic file to the
      apical foramen, and actual lengths were determined by reducing 0.5 mm from this
      length. The statistical analysis was performed by one-way ANOVA test and Tukey
      HSD post hoc procedure. P < 0.05 was considered as significant. RESULTS: No
      significant difference was found between overall mean electronic working length
      and digital radiographic length; however, prediction error (P < 0.05) was
      significant with respect to different irrigants. Among the irrigating solutions,
      chlorhexidine gluconate had the smallest distance to the actual lengths, whereas
      NaOCl had the greatest. CONCLUSION: Electronic apex locator ProPex yielded best
      result in the presence of chlorhexidine, whereas the largest error was
      demonstrated with NaOCl indicating that higher electroconductive irrigating
      solutions affect the precision of multi-frequency apex locators.

PMID- 24688562
TI  - Effects of low-level laser therapy on orthodontic tooth movement and root
      resorption after artificial socket preservation.
AB  - BACKGROUND: Low- level laser therapy has been used to stimulate the orthodontic
      tooth movements (OTM) previously. Furthermore, in the orthodontic treatments
      accompanying tooth extractions, the adjacent teeth move towards the extraction
      sites and close the space in some cases. Then, the adjacent tooth movements must
      be prevented in the treatments requiring space. Laser stimulates and at some
      doses decelerates tooth movement; it also improves healing process and enhances
      osteogenesis. Hence, it can prevent movement by osteogenesis adjacent to the
      tooth. The present study investigated the effects of low-level laser therapy on
      the OTM and root resorption following artificial socket preservation. MATERIALS
      AND METHODS: In this experimental animal trial, 16 male albino rabbits were
      selected with similar characteristics and randomly divided in two groups. Under
      general anesthesia, an artificial socket, 8 mm in height, was created in the
      mesial aspect of the first premolars of the rabbits and filled with demineralized
      freeze dried bone allograft (DFDBA). The first premolars were connected to the
      incisors using nickel titanium coil springs. In experimental group, gallium
      aluminum-arsenide (GaAlAs) laser was irritated mesial to first premolar where
      artificial socket was created continuously (808 nm). The cycle was 10 days
      irritation, 14 days rest, 10 days irritation, 14 days rest (Biostimulation mode).
      Control group was not laser irradiated. All animals were sacrificed after 48 days
      and the distance between the distal aspect of the first premolars, and the mesial
      surface of the second premolars was measured with leaf gauge. The specimens
      underwent histological assessments. Integrity of root and its resorption was
      observed under microscope calibration. The size of resorption lacunae was
      calculated in mm(2). Normality of data was proved according to Kolmogorov-Smirnov
      analysis, and Student's t-test was done. P value less than 0.05 was considered as
      significant. RESULTS: The mean OTM were 5.68 +/- 1.21 mm in the control group and
      6.0 +/- 0.99 mm in the laser irradiated teeth with no statistically significant
      differences(P > 0.75). The mean root resorption was 1.61 +/- 0.43 mm(2) and 0.18
      +/- 0.07 mm(2) in the control and experimental groups respectively being
      significantly lower in the laser irradiated teeth (P < 0.0001). CONCLUSION: The
      findings of the present study show that GaAlAs irradiation together with the
      application of DFDBA led to limited amount of the stimulated OTM. The laser beam
      irradiation in combination with alloplastic materials used for socket
      preservation could reduce the degree of root resorption significantly.

PMID- 24688563
TI  - Effects of fluoride release from orthodontic bonding materials on nanomechanical
      properties of the enamel around orthodontic brackets.
AB  - BACKGROUND: The aim of the present study is to evaluate the effects of a fluoride
      releasing composite resin bonding material on reducing enamel demineralization
      underneath and around orthodontic brackets and compare that with a conventional
      adhesive system. MATERIALS AND METHODS: Buccal surfaces of 10 intact extracted
      premolar teeth were divided into two parts with nail varnish and stainless steel
      brackets were randomly bonded by two resin composite systems: (Transbond XT) and
      (Transbond XT plus Color Change) (3M, Unitek, Monrovia, CA, USA) on two sides of
      the teeth and then samples were placed in a demineralization solution. It is
      claimed that the second system has the ability of fluoride release. Elastic
      modulus and hardness of enamel were measured with nanoindentation test in 6
      depths in 1-36 MUm from the enamel surface and in 7 regions: Control (intact
      enamel surface), underneath the brackets and also 50 and 100 MUm from the
      brackets edge. These nanomechanical features were evaluated in different regions
      and depths using analysis of variance and paired t-test (P < 0.05). RESULTS:
      Considerable difference can be seen in different depths and regions in terms of
      hardness and elastic modulus. The region under the bracket with fluoridated
      adhesive shows similar results with intact enamel, whereas these parameters in
      fluoride less side show a significant reduction (P < 0.05). CONCLUSION: Results
      show that use of resin composite bonding system with the ability of fluoride
      release for bracket bonding, may reduce demineralization of enamel around
      brackets during orthodontic treatment.

PMID- 24688564
TI  - The effect of sterilization and number of use on the accuracy of friction-style
      mechanical torque limiting devices for dental implants.
AB  - BACKGROUND: Mechanical torque limiting devices (MTLDs) are necessary tools to
      control a peak torque and achieving target values of screw component of dental
      implants. Due to probable effect of autoclaving and number of use on the accuracy
      of these devices, this study aimed to evaluate the effect of sterilization and
      number of use on the accuracy of friction-style mechanical torque limiting
      devices (F-S MTLDs) in achieving their target torque values. MATERIALS AND
      METHODS: Peak torque measurements of 15 new F-S MTLDs from three different
      manufacturers (Astra Tech, BioHorizons, Dr. Idhe) were measured ten times before
      and after 100 steam sterilization using a digital torque gauge. To simulate the
      clinical situation of aging (number of use) target torque application process was
      repeated 10 times after each sterilization cycle and the peak torque values were
      registered. Comparison of the mean differences with target torque in each cycle
      was performed using one sample t test. Considering the type of MTLDs as inter
      subject comparison, One-way repeated measure ANOVA was used to evaluate the
      absolute values of differences between devices of each manufacturer in each group
      (alpha = 0.05). RESULTS: The results of this study in Dr. Idhe group showed that,
      mean of difference values significantly differed from the target torque (P =
      0.002) until 75 cycles. In Astra Tech group, also mean of difference values with
      under estimation trend, showed a significant difference with the target torque (P
      < 0.001). Mean of difference values significantly differed from the target torque
      with under estimation trend during all the 100 cycles in BioHorizons group (P <
      0.05). CONCLUSION: The torque output of each individual device stayed in 10%
      difference from target torque values before 100 sterilization cycles, but more
      than 10% difference from the target torque was seen in varying degrees during
      these consequent cycles.

PMID- 24688565
TI  - Inflammatory response of canine gingiva to a chemical retraction agent placed at
      different time intervals.
AB  - BACKGROUND: Exposure of the gingival sulcus while controlling hemorrhage is
      prerequisites for maximizing treatment outcomes of cervical carious lesions and
      for obtaining quality impressions for the fabrication of indirect restorations
      with cervical finish lines. Gingival retraction cords saturated with different
      chemical agents are widely used for this purpose. The aim of this study was to
      investigate and compare the inflammatory potential of 15.5%ferric sulfate on
      connective tissue when placed at different times. MATERIALS AND METHODS: All
      procedures were performed on three dogs under general anesthesia. Retraction
      cords saturated with a 15.5% ferric sulfate solution were placed into the
      gingival sulcus and evaluated after 3 min and 10 min of exposure to the chemical
      agent. Excisional biopsies of the exposed gingival tissue were then obtained at
      intervals of 1 h, 24 h, and 7 days. For all specimens, histology evaluation was
      performed using light microscopy. Data collected from the microscopic images of
      all tissue specimens were analyzed by using the Wilcoxon Signed Rank and Kruskal
      Wallis Tests. P value less than 0.05 was considered as significant. RESULTS:
      Histopathologic examination of the biopsied gingival tissue revealed that the
      ferric sulfate solution caused significant tissue changes at the beginning of
      both the 3-min and 10-min gingival exposure time (P > 0.05). However, the tissue
      returned to a normal histological appearance by the end of day 7 in all cases (P
      > 0.05). CONCLUSION: The results of this study revealed that the biologic effects
      of 15.5% ferric sulfate solution are clinically acceptable and reliable when
      gingival exposure times of 3 min and 10 min are used for gingival retraction.

PMID- 24688566
TI  - The effect of shape, length and diameter of implants on primary stability based
      on resonance frequency analysis.
AB  - BACKGROUND: The aim of this in vitro study was to evaluate the effect of shape,
      diameter and length of implants on their primary stability based on resonance
      frequency analysis. MATERIALS AND METHODS: Replace select tapered and Branemark
      MK III implants were selected. Each of these two selected groups was divided into
      nine subgroups based on the implant length (IL) (short, medium and long) and the
      implant diameter (ID) (narrow platform [NP], regular platform [RP] and wide
      platform [WP]). Five implants were assigned to each of the nine subgroups.
      Implants were placed in artificial bone blocks with bone quality similar to D3
      bone. Immediately after the implant placement, its primary stability was measured
      using Osstell Mentor equipment. T-test and Tukey's honest significant difference
      Post hoc were performed for data analysis. Statistical significance was defined
      at P < 0.05. RESULTS: Replace select system showed significantly higher primary
      stability compared to the Branemark system, when using the short implants for all
      three diameters (P <= 0.004). However, in medium length implants there were no
      significant differences between the two implant systems (P >= 0.31). In long
      implants, only when the NP and RP implants were used, the Replace Select system
      showed significantly higher primary stability compared to the Branemark system (P
      = 0.000). In the replace select system, long implants had a significantly higher
      primary stability compared to medium and short length implants (P <= 0.003). In
      the NP and RP Branemark implants, short implants showed significantly lower
      primary stability compared to medium and long implants (P <= 0.002). However, in
      WP Branemark implants, primary stability increased significantly with increasing
      the IL from short to medium and from medium to long (P = 0.000). There were also
      significant differences between NP and the two other wider implants in both
      systems (P = 0.000). CONCLUSION: The use of tapered implants is recommended,
      especially, when the use of short implants is necessary. The use of RP implants
      is also preferred to WP implants, because thicker bone wall will remain in place
      when applying RP implants. Furthermore, no significant difference was observed
      between RP and WP implants.

PMID- 24688567
TI  - Distraction osteogenesis for cleft palate closure: A finite element analysis.
AB  - BACKGROUND: Current methods of closure of the cleft palate result in the
      formation of scars and impairment of growth. Distraction osteogenesis (DO) might
      be an effective means to repair or at least reduce the size of wide clefts. This
      study investigates the biomechanical aspects of this process. MATERIALS AND
      METHODS: DO simulation was applied to reduce the size of a unilateral hard palate
      cleft on a three-dimensional (3D) model of the maxilla. For the position of
      osteotomy lines, two different models were assumed, with the osteotomy line on
      the affected side in model A and on the intact side in model B. In each model, DO
      screws were placed on two different positions, anteriorly (models A1 and B1) and
      posteriorly (models A2 and B2). Displacement pattern of the bony island in each
      of the four models, reaction forces at DO locations, and von Mises stress were
      estimated. Mesh generation and data processing were carried out in the 3D finite
      element analysis package (ABAQUS V6.7-1; Simulia Corp., Providence, RI, USA).
      RESULTS: In model B2, the island moved almost evenly, assuring a more complete
      closure of the cleft. The most uniform stress distribution was found in model B1.
      CONCLUSION: The results suggest that the best positions for the DO screw and the
      osteotomy line for closure of the cleft palate are posteriorly and on the intact
      side, respectively.

PMID- 24688568
TI  - The effect of mechanical load cycling and polishing time on microleakage of class
      V glass-ionomer and composite restorations: A scanning electron microscopy
      evaluation.
AB  - BACKGROUND: Microleakage is one of the challenging concerns in direct filling
      restorations. Understanding of its related factors is important in clinical
      practice. The aim of this study was scanning electron microscopy (SEM) evaluation
      of marginal integrity in three types of tooth-colored restorative materials in
      class V cavity preparations and the effect of load cycling and polishing time on
      the microleakage. MATERIALS AND METHODS: In this in vitro experimental study,
      class V cavity preparations were prepared on the buccal and lingual surfaces of
      60 bovine incisors. The specimens were divided into three groups each containing
      20 teeth: group 1: Filtek Z350, Group 2: Fuji IX/G Coat Plus, Group 3: Fuji II
      LC/GC varnish. In each group, 2 subgroups (n = 20) were established based on
      finishing time (immediate or delayed by 24 h). All specimens were thermocycled
      (*2,000, 5-50 degrees C). In each sub groups, half of the teeth were load cycled.
      Epoxy resin replicas of 24 specimens were evaluated under field emission-SEM and
      interfacial gaps were measured. All teeth were then immersed in 0.5% basic
      fuchsin dye for 24 h, sectioned and observed under stereomicroscope. Data were
      analyzed with Kruskal-Wallis' test and Mann-Whitney U test and a comparison
      between incisal and cervical microleakage was made with Wilcoxon test. P < 0.05
      was considered as significant. RESULTS: Load cycling and filling material had a
      significant effect on microleakage, but polishing time did not. Cervical
      microleakage in Z350/load cycle/immediate polish and Fuji IX/load cycle/immediate
      or delayed polish and Fuji IX/no load cycle/immediate polish were significantly
      higher than incisal microleakage. CONCLUSION: It was concluded that the cervical
      sealing ability of Fuji IX under load cycling was better than Fuji II LC. Under
      load cycling and immediate polishing Z350 showed better marginal integrity than
      both Fuji II LC and Fuji IX. The immediate polishing didn't cause a statistically
      significant increase in microleakage of evaluated tooth-colored class V
      restorations.

PMID- 24688569
TI  - Estimation of serum beta2-microglobulin in potentially malignant disorders and
      squamous cell carcinoma of the oral cavity: A clinicopathological study.
AB  - BACKGROUND: Tumor markers are substances, which quantitatively changes in serum,
      during the tumor development, one such tumor marker is serum beta2-microglobulin
      (beta2-m). The aim of this study was to establish the role of beta2-m as a
      biochemical parameter for diagnosis and prognosis of oral carcinoma by estimation
      of serum beta2-m levels in potentially malignant lesions, conditions, and oral
      squamous cell carcinoma. MATERIALS AND METHODS: The study was carried out on 48
      subjects (16 control, 8 oral submucous fibrosis, 8 oral leukoplakia, and 16 oral
      squamous cell carcinoma patients of different stages), conducted at department of
      Oral Medicine, Kothiwal Dental College, Moradabad, India. Under aseptic
      precautions, 5 ml venous blood was drawn and serum was separated. Estimation of
      beta2-m level in serum was carried out by enzyme linked immunosorbent assay. The
      data were analyzed by using the statistical package for social sciences (SPSS
      17.0) software. Cases and controls were tested for statistical significance with
      one-way ANOVA with post-hoc Tukey's HSD. Values of P < 0.05 were considered
      significant. RESULTS: The mean serum beta2-m level in the control group was 1.173
      +/- 0.059, in potentially malignant lesions/conditions group was 1.688 +/- 0.137
      and in oral squamous cell carcinoma group was 2.835 +/- 0.0313. This progressive
      increase in serum beta2-m level was found to be highly significant (P value <
      0.001). Results of Receiver operating characteristic analysis showed beta2-m as a
      100% sensitive and specific biomarker for oral squamous cell carcinoma.
      CONCLUSION: The present study establishes beta2-m as a specific biological tumor
      marker for diagnostic and prognostic evaluation of oral squamous cell carcinoma.

PMID- 24688570
TI  - Effect of surface treatments on shear bond strength of denture teeth to denture
      base resins.
AB  - BACKGROUND: Debonding of denture teeth from denture bases is the most common
      failure in removable dentures. The purpose of this study was to evaluate the
      effect of surface treatments on shear bond strength of denture teeth to heat
      polymerized and autopolymerized denture base resins. MATERIALS AND METHODS: In
      this experimental in vitro study, 60 maxillary central incisor acrylic teeth were
      divided into two groups. Group M was polymerized with heat-polymerized acrylic
      resin (Meliodent) by compression molding technique and group F was processed by
      autopolymerized acrylic resin (Futura Gen) by injection molding technique. Within
      each group, specimens were divided into three subgroups according to the teeth
      surface treatments (n = 10): (1) ground surface as the control group (M1 and F1),
      (2) ground surface combined with monomer application (M2 and F2), and (3)
      airborne particle abrasion by 50 MUm Al2O3 (M3 and F3). The shear bond strengths
      of the specimens were tested by universal testing machine with crosshead speed of
      5 mm/min. Data were analyzed by two-way analysis of variance (ANOVA) and Tukey's
      honestly significant difference (HSD) tests (P < 0.05). RESULTS: The mean shear
      bond strengths of the studied groups were 96.40 +/- 14.01, 124.70 +/- 15.64, and
      118 +/- 16.38 N for M1, M2, and M3 and 87.90 +/- 13.48, 117 +/- 13.88, and 109.70
      +/- 13.78 N for F1, F2, and F3, respectively. The surface treatment of the
      denture teeth significantly affected their shear bond strengths to the both the
      denture base resins (P < 0.001). However, there were no significant differences
      between the groups treated by monomer or airborne particle abrasion (P = 0.29).
      The highest percentage of failure mode was mixed in Meliodent and adhesive in
      Futura Gen. CONCLUSION: Monomer application and airborne particle abrasion of the
      ridge lap area of the denture teeth improved their shear bond strengths to the
      denture base resins regardless of the type of polymerization.

PMID- 24688571
TI  - Mucopyocele of the maxillary sinus.
AB  - Mucoceles are defined as chronic, cystic lesions in the paranasal sinuses. When
      the mucocele content becomes infected, the lesion is defined as mucopyocele. Most
      mucoceles are located in the frontal and anterior ethmoid sinuses and normally
      they involve the frontal-ethmoid complex, expanding to the superior-medial region
      of the orbit, leading to ocular disorders; maxillary sinus presentation is rare.
      In the present article, the authors described a rare case of mucopyocele in the
      maxillary sinus. 

PMID- 24688572
TI  - Binder's syndrome: Report of two cases.
AB  - Binder's syndrome is an uncommon entity characterized by midfacial hypoplasia
      along with Class III incisal relationship. The individuals with this syndrome are
      easily recognizable and the syndrome is mostly associated with other
      malocclusions. The current article presents two cases of this rare syndrome and
      describes its general features. 

PMID- 24688573
TI  - Management of multiple intrusive luxative injuries: A case report with 7-year
      follow-up.
AB  - This report presents a case of severe intrusive luxation of multiple anterior
      teeth in an 11-year-old girl. The teeth were repositioned successfully by
      endodontic and orthodontic management. The case was monitored for 7 years.
      Depending on the severity of the injury, different clinical approaches for
      treatment of intrusive luxation may be used. Despite the variety of treatment
      modalities, rehabilitation of intruded teeth is always a challenge and a
      multidisciplinary approach is important to achieve a successful result. In this
      case, intruded teeth were endodontically treated with multiple calcium hydroxide
      dressings and repositioned orthodontically. The follow-up of such cases is very
      important as the repair process after intrusion is complex. After 7 years, no
      clinical or radiographic pathology was detected. 

PMID- 24688574
TI  - Treatment of severe rotations of maxillary central incisors with whip appliance:
      Report of three cases.
AB  - The routine treatment for rotated maxillary incisor is a fixed appliance, but in
      some instance the use of this method is impossible. In addition, in only limited
      cases of rotation, removable appliance is applicable. In this study, the use of a
      semi-removable appliance is presented, which has some benefits over the other
      methods. In this study, the corrections of about 70-90 degrees  rotation of the
      maxillary central incisors in different phases of mixed dentition were performed
      in three patients using whip appliance. This method was performed using a simple
      removable appliance such as Hawley appliance and whip spring that forced the
      couple to derotate the tooth. In all cases, treatment was successfully completed
      in relative short duration. Whip appliance can be recommended as an effective
      method to correct rotation of maxillary incisor in mixed dentition with several
      advantages like rapid correction. 

PMID- 24688575
TI  - Mineral Trioxide Aggregate vs. Calcium Hydroxide in Primary Molar Pulpotomy: A
      Systematic Review.
AB  - INTRODUCTION: The aim of this quantitative systematic review/meta-analysis was to
      compare the treatment outcomes of mineral trioxide aggregate (MTA) and calcium
      hydroxide (CH) in pulpotomy of human primary molars. The focused PICO question
      was "in case of pulp exposure in vital primary molars, how does MTA pulpotomy
      compare to CH in terms of clinical/radiographic success?" METHODS AND MATERIALS:
      We retrieved published randomized clinical trials (RCTs) of at least 6-month
      duration; our search included articles published up to March 2013 in five
      following databases: PubMed (Medline), Cochrane database of systematic reviews,
      Science Citation Index, EMBASE, and Google Scholar. Mantel Haenszel and Inverse
      Variance-weighted methods were applied by STATA; the relative risk (RR) was
      calculated with 95% confidence intervals (CI). RESULTS: A total of 282 English
      articles were collected. Two authors independently screened the articles and five
      RCTs were selected; data extraction and quality assessment were then carried out.
      Four RCTs were appropriate for meta-analysis according to their follow-up times
      by Mantel Haenszel method. Statistically significant difference was found between
      success rate of MTA compared to CH, with RR=0.08 (95% CI, 0.02-0.39), RR=0.19
      (95% CI, 0.08-0.46), and RR=0.38 (95% CI, 0.21-0.68) for 6-, 12-, and 24-month
      follow-ups, respectively. A significant difference was also observed for all
      included RCTs after analyses using the Inverse Variance-weighted method (RR=0.44;
      95% CI, 0.27-0.72). CONCLUSIONS: Systematic review/meta-analysis of included RCTs
      revealed that for pulpotomy of vital primary molars, MTA has better treatment
      outcomes compared to CH.

PMID- 24688577
TI  - Endodontic epidemiology.
AB  - Epidemiology is the study of disease distribution and factors determining or
      affecting it. Likewise, endodontic epidemiology can be defined as the science of
      studying the distribution pattern and determinants of pulp and periapical
      diseases; specially apical periodontitis. Although different study designs have
      been used in endodontics, researchers must pay more attention to study designs
      with higher level of evidence such as randomized clinical trials. 

PMID- 24688578
TI  - Cone-beam computed tomography for evaluation of apical transportation in root
      canals prepared by two rotary systems.
AB  - INTRODUCTION: Due to the importance of apical transportation during root canal
      preparation, the aim of the current study was to use cone-beam computed
      tomography (CBCT) to assess the extent of apical transportation caused by
      ProTaper and Mtwo files. METHODS AND MATERIALS: Forty extracted maxillary first
      molars with 19-22 mm length and 20-40 degrees of curvature were selected. The
      mesiobuccal canals were prepared using either Mtwo or ProTaper rotary files
      (n=20). CBCT images were obtained before and after canal preparation to compare
      the apical transportation in different cross-sections of mesial and distal
      surfaces. The apical transportation values were analyzed using the SPSS software.
      The results were compared with student's t-test and Mann-Whitney U test. RESULTS:
      There was no significant difference in the extent of apical transportation
      between Mtwo and ProTaper systems in different canal cross-sections. The apical
      transportation value was less than 0.1 mm in most of the specimens, which was
      clinically acceptable. CONCLUSION: Considering the insignificant difference
      between the two systems, it can be concluded that both system have low rates of
      apical transportation and can be assuredly used in clinical settings.

PMID- 24688576
TI  - An update on the management of endodontic biofilms using root canal irrigants and
      medicaments.
AB  - Microbial biofilm is defined as a sessile multicellular microbial community
      characterized by cells that are firmly attached to a surface and enmeshed in a
      self-produced matrix of extracellular polymeric substances. Biofilms play a very
      important role in pulp and periradicular pathosis. The aim of this article was to
      review the role of endodontic biofilms and the effects of root canal irrigants,
      medicaments as well as lasers on biofilms A Medline search was performed on the
      English articles published from 1982 to 2013 and was limited to papers published
      in English. The searched keywords were "Biofilms AND endodontics", "Biofilms AND
      sodium hypochlorite", "Biofilms AND chlorhexidine", "Biofilms AND MTAD",
      "Biofilms AND calcium hydroxide", "Biofilms AND ozone", "Biofilms AND lasers" and
      "Biofilms AND nanoparticles". The reference list of each article was manually
      searched to find other suitable sources of information. 

PMID- 24688579
TI  - Comparing the Fracture Rate of Hero 642, FlexMaster and Mtwo in the Simulated
      Canals.
AB  - INTRODUCTION: File fracture is one of the main procedural mishaps in endodontic
      treatment. The aim of this in vitro study was to compare the fracture rate of
      three NiTi rotary systems; Hero 642, Mtwo and FlexMaster in artificial canals.
      METHODS AND MATERIALS: In this study, bovine long bone was used. After primary
      preparation of bones, longitudinal sections with 4-cm diameter were cut and
      encoded. Subsequently, semicircular sections were prepared. A total number of 500
      canals were created in the same way; the upper 3 mm of the canals were initially
      prepared with orifice shapers and then canals were filed with FlexMaster files
      sizes 25/0.02 and 25/0.04 to 13 mm of canal length. The prepared canals were
      assigned into 3 groups of the following systems: Hero 642, Mtwo and FlexMaster.
      Six selected instruments were used from each system; the files were applied 13 mm
      along the canals for 10 sec with manufacturer's suggested speed and torque. The
      number of the canals prepared by each file before its separation was recorded;
      finally the data was analyzed with ANOVA test. RESULTS: Mean number of prepared
      canals in Mtwo, FlexMaster and Hero groups before file separation was 15, 25 and
      32, respectively. CONCLUSION: RESULTS of this study showed that the number of
      prepared canals by Hero 642 was more than FlexMaster and Mtwo systems.

PMID- 24688581
TI  - The ability of triple antibiotic paste and calcium hydroxide in disinfection of
      dentinal tubules.
AB  - INTRODUCTION: The purpose of this in vitro study was to compare the ability of
      triple antibiotic paste (TAP) to calcium hydroxide (CH) in disinfecting dentinal
      tubules. MATERIAL AND METHODS: Sixty root blocks were obtained from extracted
      single-rooted human teeth. The root canals were enlarged with Gates-Glidden
      drills up to size 3 and were contaminated with Enterococcus. faecalis (E.
      faecalis), and then left for 21 days. The contaminated blocks were treated with
      saline (as negative control), CH or TAP. Dentin debris was obtained at the end of
      first and 7th days, using Gates-Glidden drills sizes 4 and 5 from two different
      depths of 100 and 200 um. The vital bacterial load was assessed by counting the
      number of colony forming units (CFUs). The data was analyzed with the Kruskal
      Wallis H and Dunn Post-Hoc tests. The Wilcoxon Signed Ranks test was used to
      check for differences in bacterial growth at both depths (P<0.05). RESULTS: In
      comparison with CH, the TAP significantly decreased the number of CFUs in both
      depths and time intervals (P<0.001), while the CH group showed a moderate
      antibacterial effect. CONCLUSION: TAP is more effective in disinfecting the canal
      against E. faecalis compared to CH.

PMID- 24688580
TI  - A Comparison of Apical Transportation in Severely Curved Canals Induced by
      Reciproc and BioRaCe Systems.
AB  - INTRODUCTION: Preserving the apical root structure during cleaning and shaping of
      the canal has always been a challenge in endodontics particularly when the root
      canals are curved. The purpose of this in vitro study was to compare the apical
      transportation induced by the Reciproc and BioRaCe rotary systems in preparing
      the mesiobuccal root canal of the human maxillary molars. MATERIALS AND METHODS:
      The mesiobuccal canals of sixty extracted maxillary molars with curvature angle
      of 25-35 were selected and randomly assigned into two groups. Each canal was
      prepared by either Reciproc or BioRaCe rotary systems. A double-digital
      radiographic technique and AutoCAD software were used to compare the apical
      transportation at 0.5, 1, 2, 3, 4 and 5 mm distances from the working length
      (WL). The distance between the master apical rotary file and the initial K-file
      in the superimposed radiographs determined the amount of apical transportation.
      An independent t-test was used to compare the groups. The statistical significant
      level was set at 0.05. RESULTS: Apical transportation of the Reciproc group was
      significantly greater than the BioRaCe group in all distances (P<0.001). The
      maximum apical transportation occurred in the Reciproc group at 0.5 mm from the
      WL (0.048+/-0.0028 mm) and the minimum occurred for BioRaCe at 5 mm from the WL
      (0.010+/-0.0005 mm). CONCLUSIONS: The Reciproc system produced significantly more
      apical transportation than the BioRaCe, but this fact does not seem to negatively
      alter the clinical success or quality of root canal treatment.

PMID- 24688582
TI  - The Impact of Three Different Canal Lubricants on Fracture, Deformity and Metal
      Slivering of ProTaper Rotary Instruments.
AB  - INTRODUCTION: The aim of this in vitro study was to evaluate the effect(s) of
      three canal lubricants i.e. sodium hypochlorite, RC-Prep as the paste form of
      ethylenediaminetetraacetic acid (EDTA) and aqueous EDTA on the
      occurrence/incidence of fracture, deformity and metal slivering of ProTaper
      rotary instruments. METHODS: A total of 120 mesial canals (i.e. mesiobuccal and
      mesiolingual) of first mandibular molars or buccal canals (i.e. mesiobuccal and
      distobuccal) of first maxillary molars, with curvatures of 10-20 degrees were
      selected and randomly divided into three groups of forty samples each. These
      selected canals all had approximate 19-21 mm working length and apical diameter
      equal to a #15 K-file. In each group, the root canals were prepared using
      ProTaper rotary instruments with an electric motor using one of the three
      aforementioned irrigants. Subsequently, samples were compared to each other at
      different magnifications (16*, 20*, 40* and 57*) for any fracture, deformity or
      metal slivering, by the Cox regression analysis. RESULTS: The fractures rate of
      samples in RC-Prep group was significantly higher compared to other groups
      (P=0.01). No evidence of instrument deformity was detected in any groups. A
      statistically significant reverse relation between metal slivering and instrument
      fracture was observed. CONCLUSIONS: Application of aqueous EDTA and/or sodium
      hypochlorite as intracanal lubricants caused less fracture of ProTaper
      instruments compared to canal lubrication with RC-Prep.

PMID- 24688583
TI  - A scanning electron microscope study on the effect of an experimental irrigation
      solution on smear layer removal.
AB  - INTRODUCTION: The aim of this in vitro study was to evaluate the effect of an
      experimental irrigation solution, containing two different concentrations of
      papain, Tween 80, 2% chlorhexidine and EDTA, on removal of the smear layer.
      METHODS AND MATERIALS: Thirty-six single-rooted teeth were divided into two
      experimental groups (n=12) and two positive and negative control groups of six.
      The canals were prepared with BioRaCe instruments up to BR7 (60/0.02). In group
      1, canals were irrigated with a combination of 1% papain, 17% EDTA, Tween 80 and
      2% CHX; in group 2, canals were irrigated with a combination of 0.1% papain, 17%
      EDTA, Tween 80 and 2% CHX. In group 3 (the negative control), the canal was
      irrigated with 2.5% NaOCl during instrumentation and at the end of preparation
      with 1 mL of 17% EDTA was used; in group 4 (positive control), normal saline was
      used for irrigation. The amount of the remaining smear layer was quantified
      according to Hulsmann method using scanning electron microscopy (SEM). Data was
      analyzed by the Kruskal-Wallis and Mann-Whitney tests. RESULTS: Two-by-two
      comparisons of the groups revealed no significant differences in terms of smear
      layer removal at different canal sections between the negative control group
      (standard regiment for smear layer removal) and 1% papain groups (P<0.05).
      CONCLUSION: Under the limitations of the present study, combination of 1% papain,
      EDTA, 2% chlorhexidine and Tween 80 can effectively remove smear layer from canal
      walls.

PMID- 24688584
TI  - A study on biocompatibility of three endodontic sealers: intensity and duration
      of tissue irritation.
AB  - INTRODUCTION: Several studies have evaluated the inflammatory reaction triggered
      by Epiphany (EPH), a contemporary endodontic sealer. However, they used
      conventional parameters, which need additional analysis to better understand the
      reactions induced by this sealer compared to other traditional sealers. METHODS
      AND MATERIALS: The intensity and time span of tissue irritations for three
      endodontic sealers were assessed by inflammatory reactions, fibrous capsule
      measurement and mast cell counts. Tubes containing freshly mixed EPH, AH plus
      (AHP) and Endofill (ENF) were subcutaneously implanted into the backs of 28
      Wistar rats. The side wall of the tube was used as the control. At 14, 21, 42 and
      60 days, the connective tissue surrounding the implants (n=7) was stained for
      histopathological analysis. The Friedman test was applied to compare the results.
      The level of significance was set at 0.05. RESULTS: At days 14 and 21, a
      significant difference among the groups was observed, with the ENF showing the
      worst tissue response (P<0.001). ENF remained the most aggressive sealer at 42
      and 60 days, compared with EPH (P<0.05). No differences were found for the
      fibrous capsule thicknesses among the groups in each period. The number of mast
      cells per field did not show difference among the sealers at 21 and 60 days.
      CONCLUSIONS: EPH and AHP elicited similar patterns of irritation, as demonstrated
      by the inflammatory scores and fibrous capsule thicknesses. ENF caused the
      highest degree of tissue damage. The increase in mast cell counts observed during
      the early and late periods shows the possibility of late hypersensitivity to the
      test materials.

PMID- 24688585
TI  - Marginal adaptation of new bioceramic materials and mineral trioxide aggregate: a
      scanning electron microscopy study.
AB  - INTRODUCTION: This study aimed to compare the marginal adaptation of new
      bioceramic materials, EndoSequence Root Repair Material (ERRM putty and ERRM
      paste), to that of mineral trioxide aggregate (MTA) as root-end filling
      materials. MATERIALS AND METHODS: Thirty-six extracted human single-rooted teeth
      were prepared and obturated with gutta-percha and AH-26 sealer. The roots were
      resected 3 mm from the apex. Root-end cavities were then prepared with an
      ultrasonic retrotip. The specimens were divided into three groups (n=12) and
      filled with MTA, ERRM putty or ERRM paste. Epoxy resin replicas from the resected
      root-end surfaces and longitudinally sectioned roots were fabricated. The gaps at
      the material/dentin interface were measured using scanning electron microscope
      (SEM). Transversal, longitudinal, and overall gap sizes were measured for each
      specimen. The data were analyzed using the Kruskal-Wallis test. RESULTS: In
      transversal sections, no significant difference was found between MTA, ERRM putty
      and ERRM paste (P=0.31). However, in longitudinal sections, larger gaps were
      evident between ERRM paste and dentinal walls compared to MTA and ERRM putty
      (P=0.002 and P=0.033, respectively). Considering the overall gap size values, the
      difference between three tested materials was not statistically significant
      (P=0.17). CONCLUSION: Within the limits of this study, the marginal adaptation of
      ERRM paste and putty was comparable to that of MTA. However, ERRM putty might be
      more suitable for filling the root-end cavities because of its superior
      adaptation compared to ERRM paste in longitudinal sections.

PMID- 24688586
TI  - Extraoral Retrograde Root Canal Filling of an Orthodontic-induced External Root
      Resorption Using CEM Cement.
AB  - Inflammatory external root resorption (IERR) after orthodontic treatments is an
      unusual complication. This case report describes a non-vital maxillary premolar
      with symptomatic extensive IERR (with a crown/root ratio of 1:1) after receiving
      orthodontic treatment. The first appointment included drainage, chemo-mechanical
      preparation of the canal and intra-canal medication with calcium hydroxide (CH)
      along with prescription of analgesic/antibiotic. The subsequent one-week follow
      up revealed the persistence of symptoms and formation of a sinus tract. Finally,
      extraoral endodontic treatment was planned; the tooth was atraumatically
      extracted and retrograde root canal filling with calcium enriched mixture (CEM)
      cement was placed followed by tooth replantation. Clinical signs/symptoms
      subsided during 7 days postoperatively. The sinus tract also resolved after one
      week. Six-month and one-year follow-ups revealed complete healing and a fully
      functional asymptomatic tooth. This case study showed favorable outcomes in a
      refractory periapical lesion associated with orthodontically induced extensive
      IERR. The chemical as well as biological properties of CEM cement may be a
      suitable endodontic biomaterial for these cases. 

PMID- 24688587
TI  - Report of a rare case: a maxillary first molar with seven canals confirmed with
      cone-beam computed tomography.
AB  - INTRODUCTION: Coronal anatomic variations in permanent maxillary molars are
      unusual; conversely variations involving the number of root canals or number of
      roots are more common. METHODS AND MATERIALS: This case report presents a
      successful nonsurgical endodontic therapy of left maxillary first molar with
      three roots and seven root canals. This unusual morphology was diagnosed using a
      dental operating microscope (DOM) and confirmed with the help of cone-beam
      computed tomography (CBCT) images. RESULTS: CBCT axial images showed that both of
      the palatal and distobuccal roots had Vertucci type II canal pattern, whereas the
      mesiobuccal root canal showed a Sert and Bayirli's type XV configuration.
      CONCLUSION: The use of a DOM and CBCT imaging in endodontically challenging cases
      can facilitate a better understanding of the complex root canal anatomy, which
      ultimately enables the clinician to explore the root canal system, and therefore
      treat it far more efficiently.

PMID- 24688588
TI  - Retreatment of a mandibular second premolar with three roots: a case report.
AB  - Mandibular premolars have earned a reputation for having aberrant anatomy. The
      occurrence of three canals with three separate foramina in mandibular premolars
      is very rare. If predictable treatment of a three rooted mandibular premolar is
      planned, precise knowledge of clinical and radiographic anatomy is absolutely
      necessary. These teeth may also require special shaping and obturating
      techniques. This article reports and discusses the treatment recommendations for
      an unusual occurrence of three canals with three separate foramina in a second
      mandibular premolar. 

PMID- 24688590
TI  - Heart rate variability and complementary medicine.

PMID- 24688589
TI  - Chinese herbal medicine on dyslipidemia: progress and perspective.
AB  - Dyslipidemia is an independent risk factor of cardiovascular diseases. The
      statins are a milestone in the primary and second prevention of cardiovascular
      diseases and significantly improved its prognosis. Along with the long-term
      treatment with statins in combination with other hypolipidemic drugs or alone,
      its safety has attracted a particular attention in clinic, such as the elevation
      of transaminase and rhabdomyolysis, which have raised an idea of developing the
      other types of lipid-lowering agents from botanic materials. Traditional Chinese
      medicine (TCM) has been used in clinical practice for more than 2000 years in
      China and showed some beneficial effects for human health and many diseases.
      Recently, many studies demonstrated a favorable effect of TCM for treating
      dyslipidemia; however, its mechanism remains unclear or totally unknown. The
      progress and perspective of studies on dyslipidemia with single Chinese herb and
      its monomers or effective extracts during the past 10 years are discussed in the
      present review. 

PMID- 24688591
TI  - Assessment of Registration Information on Methodological Design of Acupuncture
      RCTs: A Review of 453 Registration Records Retrieved from WHO International
      Clinical Trials Registry Platform.
AB  - Background. This review provides the first methodological information assessment
      of protocol of acupuncture RCTs registered in WHO International Clinical Trials
      Registry Platform (ICTRP). Methods. All records of acupuncture RCTs registered in
      the ICTRP have been collected. The methodological design assessment involved
      whether the randomization methods, allocation concealment, and blinding were
      adequate or not based on the information of registration records (protocols of
      acupuncture RCTs). Results. A total of 453 records, found in 11 registries, were
      examined. Methodological details were insufficient in registration records; there
      were 76.4%, 89.0%, and 21.4% records that did not provide information on
      randomization methods, allocation concealment, and blinding respectively. The
      proportions of adequate randomization methods, allocation concealment, and
      blinding were only 107 (23.6%), 48 (10.6%), and 210 (46.4%), respectively. The
      methodological design improved year by year, especially after 2007. Additionally,
      methodology of RCTs with ethics approval was clearly superior to those without
      ethics approval and different among registries. Conclusions. The overall
      methodological design based on registration records of acupuncture RCTs is not
      very well but improved year by year. The insufficient information on
      randomization methods, allocation concealment, and blinding maybe due to the
      relevant description is not taken seriously in acupuncture RCTs' registration. 

PMID- 24688592
TI  - Millipedes as food for humans: their nutritional and possible antimalarial value
      a first report.
AB  - The first record of millipedes (Diplopoda) being regularly used for food by
      humans (the Bobo people of Burkina Faso) is given, including information on how
      the millipedes are prepared. The species in question are Tymbodesmus falcatus
      (Karsch, 1881) and Sphenodesmus sheribongensis (Schiotz, 1966) (Gomphodesmidae)
      and an unidentified species of Spirostreptidae. New information on the
      nutritional value of millipedes is provided; unsaturated fatty acids, calcium,
      and iron contents are particularly high. The millipedes' defensive secretions,
      hydrogen cyanide and benzoquinones, present a severe challenge for the spread of
      millipedes as an everyday food source. On the other hand, the possibility that
      benzoquinones may act as insect-repellents, as known from studies on nonhuman
      primates, and that sublethal cyanide ingestion may enhance human innate
      resistance to malaria, suggests promising ethnomedical perspectives to our
      findings. 

PMID- 24688593
TI  - Analyzing the study of using acupuncture in delivery in the past ten years in
      china.
AB  - The use of acupuncture in inducing delivery has a long history in China. With
      progress over time, it has been applied in many aspects. For further study of
      acupuncture in delivery, this paper analyzed the papers using acupuncture in
      delivery in the past ten years in mainland China. 87 literatures were picked out
      by searching relevant electronic databases and bibliographies of relevant
      journals. The analysis showed randomized controlled trials that were the major
      type of research, while preclinical researches and literature reviews only
      account for around ten percent, respectively. Clinical researches indicated that
      acupuncture can relieve labor pain, promote maternal uterine contraction, shorten
      birth process, and treat postpartum disorders. Preclinical researches found that
      acupuncture can adjust certain hormones and improve uterus contraction of late
      stage pregnant rats. However, due to lack of large multicenter randomized
      controlled clinical trials, standardized evaluations of clinical effects in
      clinical researches and detailed mechanism study in preclinical researches and
      unequivocal conclusions about the effectiveness, efficacy, and mechanisms of
      acupuncture in this field cannot be obtained from those researches yet. Further
      clinical and preclinical studies about the use of acupuncture in delivery with
      improved methodology is still needed. 

PMID- 24688594
TI  - Hexane Fractions of Bupleurum falcatum L. Stimulates Glucagon-Like Peptide-1
      Secretion through G beta gamma -Mediated Pathway.
AB  - Bupleurum falcatum L. has been used traditionally as a medicinal herb in Korean
      medicine. The hexane fraction of BF (HFBF), which was profiled with Direct
      Analysis in Real Time-Mass Spectrometry (DART-MS), activates the secretion of
      glucagon-like peptide-1 (GLP-1) in NCI-H716 cells significantly. We performed a
      microarray analysis and GLP-1 ELISA assay, as well as calcium imaging experiments
      with inhibitors, to investigate the mechanism of action of the HFBF. Through the
      microarray analysis, it was found that the ITPR2 gene that encodes the inositol
      1,4,5-trisphosphate (IP3) receptor is up-regulated and the HFBF induces cell
      depolarization by inhibiting the voltage-gated channel expression in NCI-H716
      cells. In addition, we found that the intracellular calcium in NCI-H716 cells,
      with Gallein, U73122, and 2APB as inhibitors, was decreased. These results
      suggest that the HFBF activates the GLP-1 secretion through the G betagamma
      pathways in the enteroendocrine L cells after treatment with the HFBF. 

PMID- 24688595
TI  - Quantitative estimation of temperature variations in plantar angiosomes: a study
      case for diabetic foot.
AB  - Thermography is a useful tool since it provides information that may help in the
      diagnostic of several diseases in a noninvasive and fast way. Particularly,
      thermography has been applied in the study of the diabetic foot. However, most of
      these studies report only qualitative information making it difficult to measure
      significant parameters such as temperature variations. These variations are
      important in the analysis of the diabetic foot since they could bring knowledge,
      for instance, regarding ulceration risks. The early detection of ulceration risks
      is considered an important research topic in the medicine field, as its objective
      is to avoid major complications that might lead to a limb amputation. The absence
      of symptoms in the early phase of the ulceration is conceived as the main
      disadvantage to provide an opportune diagnostic in subjects with neuropathy.
      Since the relation between temperature and ulceration risks is well established
      in the literature, a methodology that obtains quantitative temperature
      differences in the plantar area of the diabetic foot to detect ulceration risks
      is proposed in this work. Such methodology is based on the angiosome concept and
      image processing. 

PMID- 24688596
TI  - A new high-resolution spectral approach to noninvasively evaluate wall
      deformations in arteries.
AB  - By locally measuring changes on arterial wall thickness as a function of
      pressure, the related Young modulus can be evaluated. This physical magnitude has
      shown to be an important predictive factor for cardiovascular diseases. For
      evaluating those changes, imaging segmentation or time correlations of ultrasonic
      echoes, coming from wall interfaces, are usually employed. In this paper, an
      alternative low-cost technique is proposed to locally evaluate variations on
      arterial walls, which are dynamically measured with an improved high-resolution
      calculation of power spectral densities in echo-traces of the wall interfaces, by
      using a parametric autoregressive processing. Certain wall deformations are
      finely detected by evaluating the echoes overtones peaks with power spectral
      estimations that implement Burg and Yule Walker algorithms. Results of this
      spectral approach are compared with a classical cross-correlation operator, in a
      tube phantom and "in vitro" carotid tissue. A circulating loop, mimicking heart
      periods and blood pressure changes, is employed to dynamically inspect each
      sample with a broadband ultrasonic probe, acquiring multiple A-Scans which are
      windowed to isolate echo-traces packets coming from distinct walls. Then the new
      technique and cross-correlation operator are applied to evaluate changing
      parietal deformations from the detection of displacements registered on the wall
      faces under periodic regime. 

PMID- 24688597
TI  - The role of [(18)F]FDG-PET/CT in staging and treatment planning for volumetric
      modulated Rapidarc radiotherapy in cervical cancer: experience of the European
      Institute of Oncology, Milan, Italy.
AB  - RATIONALE: to evaluate the role of 18F-fluorodeoxyglucose positron emission
      tomography ([(18)F]FDG-PET) integrated with computer tomography (CT) scan
      [(18)F]FDG-PET/CT in the staging and target volume definition in Intensity
      Modulated RapidarcTM Delivery (RA-IMRT) in cervical cancer. METHODS: From June
      2010 to December 2011, 66 patients affected by cervical cancer, candidates for
      definitive or adjuvant radiochemotherapy, underwent standard staging with CT and
      magnetic resonance imaging (MRI). All patients underwent [(18)F]FDG-PET/CT in
      order to exclude distant metastases and to define gross tumor volume (GTV). 40
      and 26 patients received exclusive and adjuvant radiotherapy, respectively. RA
      IMRT with simultaneous integrated boost (SIB) to the positive disease technique
      was employed. RESULTS: [(18)F]FDG-PET/CT has changed the stage, and radiotherapy
      treatment planning was modified in 25% and 7.7 % of patients that received
      definitive and adjuvant radiotherapy, respectively. Particularly [(18)F]FDG
      PET/CT imaging showed metabolically active tumor in lymph nodes area, therefore
      the stage and the treatment planning changed for these patients. CONCLUSIONS:
      [(18)F]FDG-PET/CT leads to a better staging and definition of disease and has the
      potential of showing lymph-node metastasis not only within the pelvis but also in
      the para-aortic area. In addition, [(18)F]FDG-PET/CT is useful for better
      definition of the target volume and to produce a 'dose painted' treatment. This
      might also open the field for escalation dose regimens.

PMID- 24688599
TI  - Using Social Networking Sites for Communicable Disease Control: Innovative
      Contact Tracing or Breach of Confidentiality?
AB  - Social media applications such as Twitter, YouTube and Facebook have attained
      huge popularity, with more than three billion people and organizations predicted
      to have a social networking account by 2015. Social media offers a rapid avenue
      of communication with the public and has potential benefits for communicable
      disease control and surveillance. However, its application in everyday public
      health practice raises a number of important issues around confidentiality and
      autonomy. We report here a case from local level health protection where the
      friend of an individual with meningococcal septicaemia used a social networking
      site to notify potential contacts.

PMID- 24688598
TI  - Expression of the metastasis suppressor BRMS1 in uveal melanoma.
AB  - AIMS: To determine the expression of breast metastasis suppressor 1 (BRMS1) in
      human uveal melanoma (UM) tissues and cell lines. In addition, we intend to
      establish a possible association between BRMS1 expression and the presence of
      metastatic disease. METHODS: Thirty-one formalin-fixed paraffin-embedded tissues
      from enucleated eyes of patients with UM were immunostained. Clinical
      pathological data were obtained, including age, tumour location, largest
      dimension, cell type, and occurrence of metastasis. The expression of BRMS1 mRNA
      in four human UM cell lines was determined by real-time reverse transcriptase
      polymerase chain reaction, and protein expression was assessed by
      immunocytochemistry and western blot. The association between BRMS1
      immunostaining and location, largest tumour dimension, and tumour cell type was
      determined using the correlation coefficient test. The association between BRMS1
      immunostaining and the incidence of metastasis was assessed using Kaplan-Meier
      analysis. RESULTS: Of the 31 cases of UM, 24 (77.42%) stained positive and seven
      (22.58%) negative for BRMS1. From the positively stained tumours, 21 (87.50%)
      showed cytoplasmatic staining. Macrophages were usually positive when present in
      the tumour and staining intensity was generally higher than in UM cells. BRMS1
      mRNA was present in all four human UM cell lines, as well as cytoplasmatic
      immunoexpression of BRMS1. Immunoblotting showed variable BRMS1 protein levels
      between the different cell lines. No statistically significant correlation was
      found between BRMS1 protein expression and survival (P = 0.69), tumour cell type
      (P = 0.68), largest tumour dimension (P = 0.75), and tumour location (P = 0.11).
      CONCLUSIONS: BRMS1 is expressed in UM both at the mRNA and protein level;
      however, neither was associated with any of the prognosticor outcome parameters
      that we tested.

PMID- 24688600
TI  - Intralesional collagenase in the treatment of Peyronie's disease.
AB  - The objective of intralesional pharmacotherapy in the treatment of Peyronie's
      disease is to deliver large doses of pharmacologic agents that can have a local
      effect on wound remodeling, with minimal side effects. Guidelines for the
      treatment of peyronie's disease published in the Journal of Sexual Medicine and
      the European Association of Urology offer no grade A evidence of efficacy with
      multiple agents such as steroids, verapamil and interferon. Intralesional
      collagenase is the first drug to be approved by the United States Food and Drug
      Administration for the treatment of Peyronie's disease. This is based on grade A
      evidence. The purpose of this update is to review the literature and current data
      on intralesional collagenase in the treatment of Peyronie's disease. 

PMID- 24688601
TI  - Antibiotic resistance in pediatric urology.
AB  - Antibiotics are a mainstay in the treatment of bacterial infections, though their
      use is a primary risk factor for the development of antibiotic resistance.
      Antibiotic resistance is a growing problem in pediatric urology as demonstrated
      by increased uropathogen resistance. Lack of urine testing, nonselective use of
      prophylaxis, and poor empiric prescribing practices exacerbate this problem. This
      article reviews antibiotic utilization in pediatric urology with emphasis on
      modifiable practice patterns to potentially help mitigate the growing rates of
      antibiotic resistance. This includes urine testing to only treat when indicated
      and tailor broad-spectrum therapy as able; selective application of antibiotic
      prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis
      with counseling regarding the importance of compliance; and using local
      antiobiograms, particularly pediatric-specific antiobiograms, with inpatient
      versus outpatient data. 

PMID- 24688602
TI  - Holmium laser enucleation of the prostate: a review of the clinical trial
      evidence.
AB  - Transurethral resection of the prostate (TURP) has remained the procedure of
      choice for the surgical treatment of bladder outflow obstruction for almost five
      decades, but holmium laser enucleation of the prostate (HoLEP) is now emerging as
      a challenger as the gold standard procedure. This review summarizes the evidence
      base for HoLEP, with particular reference to randomized, controlled (level 1)
      evidence. 

PMID- 24688603
TI  - The Prostate Health Index: a new test for the detection of prostate cancer.
AB  - A major focus in urologic research is the identification of new biomarkers with
      improved specificity for clinically-significant prostate cancer. A promising new
      test based on prostate-specific antigen (PSA) is called the Prostate Health Index
      (PHI), which has recently been approved in the United States, Europe and
      Australia. PHI is a mathematical formula that combines total PSA, free PSA and [
      2] proPSA. Numerous international studies have consistently shown that PHI
      outperforms its individual components for the prediction of overall and high
      grade prostate cancer on biopsy. PHI also predicts the likelihood of progression
      during active surveillance, providing another noninvasive modality to potentially
      select and monitor this patient population. This article reviews the evidence on
      this new blood test with significant promise for both prostate cancer screening
      and treatment decision-making. 

PMID- 24688604
TI  - Role of ultrasound in the understanding and management of vasculitis.
AB  - Vasculitis is characterized by a circumferential vessel-wall thickening ('halo'),
      which can be visualized by modern imaging techniques. In particular, the
      resolution of ultrasound has increased to 0.1 mm. Ultrasound detects
      abnormalities that are pathognomonic even in arteries with a diameter below 1 mm.
      It is particularly helpful in the diagnosis of large-vessel vasculitides, such as
      classic temporal arteritis, large-vessel giant-cell arteritis (GCA), Takayasu
      arteritis and idiopathic aortitis. Echocardiography is important for determining
      cardiac involvement in Takayasu arteritis and also for examining the coronary
      arteries of children with suspected Kawasaki disease, which is a medium-vessel
      vasculitis. In small vessel vasculitides ultrasound has only a role for
      determining the distribution or organ involvement. Fast-track clinics for the
      diagnosis of GCA help to initiate treatment before complications such as
      blindness occur; patients receive appointments within 24 h in these clinics.
      Clinical examination and ultrasound of temporal and axillary arteries are
      performed by an experienced rheumatologist. In most cases this is able to
      determine if GCA is present. Temporal artery biopsy can be still carried out in
      ambivalent cases. The wall swelling of temporal arteries disappears after 2-3
      weeks of glucocorticoid treatment. After 3 days of treatment, diagnosis becomes
      more difficult with ultrasound in some cases. In larger arteries, such as the
      axillary arteries, wall thickening disappears within months. It tends to be
      darker (more hypoechoic) in acute disease because of oedema. 

PMID- 24688605
TI  - Role of sclerostin in bone and cartilage and its potential as a therapeutic
      target in bone diseases.
AB  - Sclerostin is a small protein expressed by the SOST gene in osteocytes, bone
      cells that respond to mechanical stress applied to the skeleton and appear to
      play an important role in the regulation of bone remodeling. When sclerostin
      binds to its receptors on the cell surface of osteoblasts, a downstream cascade
      of intracellular signaling is initiated, with the ultimate effect of inhibiting
      osteoblastic bone formation. Recent studies have shown that the SOST gene is also
      expressed by articular chondrocytes and that modulation of its activity may have
      effects on articular cartilage and subchondral bone. The role of sclerostin in
      the pathogenesis of osteoarthritis in humans has not yet been defined, and the
      potential utility of treating osteoarthritis with interventions that alter
      sclerostin is not known. Rare genetic skeletal disorders in humans with low
      sclerostin levels, such as sclerosteosis and van Buchem disease, have been
      associated with a high bone mineral density (BMD) phenotype and low risk of
      fractures. This has led to the concept that antisclerostin interventions might be
      useful in the treatment of patients with osteoporosis and skeletal disorders
      associated with low bone mass. Compounds that inhibit sclerostin have been shown
      to stimulate bone formation and reduce bone resorption, with a robust increase in
      BMD. Investigational monoclonal antibodies to sclerostin, including romosozumab,
      blosozumab, and BPS804, have advanced to phase II clinical trials or beyond. If
      antisclerostin therapy is found to have beneficial effects on clinical endpoints,
      such as reduction of fracture risk or improvement in quality of life in patients
      with osteoarthritis, with a favorable balance of benefit and risk, then this
      class of compounds may become a prominent addition to the options for therapy of
      osteoporosis and other skeletal disorders. 

PMID- 24688606
TI  - Experience with rituximab in the treatment of antineutrophil cytoplasmic antibody
      associated vasculitis.
AB  - Prior to the 1970s, severe cases of antineutrophil cytoplasmic antibody
      associated vasculitis (AAV) were thought to be invariably fatal. However, the use
      of cyclophosphamide-based treatment regimens fundamentally altered disease
      outcomes, transforming AAV into a manageable, chronic illness. Despite the
      tremendous success of cyclophosphamide in the treatment of AAV, there remained a
      need for alternative therapies, due to high rates of treatment failures and
      significant toxicities. In recent years, with the introduction of targeted
      biologic response modifiers into clinical practice, many have hoped that the
      treatment options for AAV could be expanded. Rituximab, a chimeric monoclonal
      antibody directed against the B-lymphocyte protein CD20, has been the most
      successful biologic response modifier to be used in AAV. Following the first
      report of its use in AAV in 2001, experience with rituximab for treatment of AAV
      has rapidly expanded. Rituximab, in combination with glucocorticosteroids, is now
      well established as a safe and effective alternative to cyclophosphamide for
      remission induction for severe manifestations of granulomatosis with polyangiitis
      and microscopic polyangiitis. In addition, initial experiences with rituximab for
      remission maintenance in these diseases have been favorable, as have experiences
      for remission induction in eosinophilic granulomatosis with polyangiitis. 

PMID- 24688607
TI  - Regulation of host innate immunity by hepatitis C virus: crosstalk between
      hepatocyte and NK/DC.
AB  - Hepatitis C virus (HCV) infection in humans is remarkably efficient in
      establishing viral persistence, leading to the development of liver cirrhosis and
      hepatocellular carcinoma. CD8+ T cells are involved in controlling HCV infection;
      but, in chronic HCV patients, severe CD4+ and CD8+ T cell dysfunction has been
      observed. This suggests that HCV may employ numerous mechanisms to counteract or
      possibly suppress the host T cell responses. The primary site of HCV replication
      occurs within hepatocytes in the liver. As a result of liver enodothelial cells
      perforated by fenestrations, parenchymal cells (hepatocytes) are not separated by
      a basal membrane, and thereby HCV-infected hepatocytes are extensively capable of
      interacting with innate immune cells including NK, DC. Recent studies reveal that
      the function of NK and DC function is significantly impaired in chronic HCV
      patients. Given a critical role of NK and DC in limiting HCV replication at the
      early phase of viral infection, it is likely that HCV-infected hepatocytes might
      be responsible for impairing NK and DC function by enhancing the expression of
      immunoregulatory molecules (either soluble or cell surface). Thus, this
      impairment of innate immunity attributes to the failure of generating effective T
      cell responses to clear HCV infection. In this article, we will review studies
      highlighting the regulation of innate immunity by HCV and crosstalk between
      hepatocytes and NK/DC in the hepatic environment.

PMID- 24688609
TI  - First Case of Liver Abscess in Scandinavia Due to the International Hypervirulent
      Klebsiella Pneumoniae Clone ST23.
AB  - This is the first case report from Scandinavia of a pyogenic liver abscess caused
      by a Klebsiella pneumoniae isolate belonging to the international hyper virulent
      clone ST23. The patient, an 85-year old Caucasian, had no history of foreign
      travel or any classical predisposing factors for infection. The isolate was
      hypermucoviscous of capsular serotype K1 and carried the virulence factors
      aerobactin, allS, kfu and rmpA. 

PMID- 24688608
TI  - Study on Certain Biomarkers of Inflammation in Psoriasis Through "OMICS"
      Platforms.
AB  - BACKGROUND: In recent years, research on psoriasis has focused on the
      identification of biomarkers for the diagnosis, pathogenesis, prognosis, or
      therapeutic response of the disease. These studies could provide insights into
      the susceptibility and natural history of psoriasis. The identification of
      biomarkers related to comorbidities in psoriasis, such as arthritis,
      cardiovascular disease, and the metabolic syndrome, is of special clinical
      interest. MATERIALS AND METHODS: We performed an extensive review on psoriasis
      biomarkers, including cytokine and growth factors, in the literature published
      between 1997 and 2013, including cross-references of any retrieved articles. We
      also included some data from our own studies. RESULTS: This review presents
      current knowledge of soluble biomarkers in psoriasis, including cytokines,
      chemokines, proangiogenic mediators, growth factors, antimicrobial proteins,
      neuropeptides, and oxidative stress markers. CONCLUSION: In conclusion, a number
      of studies have been conducted with the aim of establishing soluble biomarkers
      for psoriasis. Most of the biomarkers that have been studied do not meet the
      criteria for a clinically useful biomarker. Further work is needed to establish a
      role for soluble biomarkers in the diagnosis and treatment of psoriasis, with a
      special focus on biomarkers for psoriasis comorbidities, such as arthritis,
      cardiovascular disease, and the metabolic syndrome.

PMID- 24688611
TI  - Pharmacist attire and its impact on patient preference.
AB  - OBJECTIVE: To determine the influence of demographics on patient preferences for
      community pharmacist attire. METHODS: A 10-item questionnaire was developed and
      administered to patients visiting a chain pharmacy or an independent pharmacy in
      the Birmingham, Alabama metropolitan area. Mann-Whitney was used to examine if
      statistical differences existed in chain versus independent pharmacy patient's
      selections based on pharmacist attire. RESULTS: A statistically significant
      difference in patient preference for pharmacist attire between the settings in
      regards to which pharmacist patients felt was more approachable was observed;
      51.2% of chain pharmacy respondents compared to 30% of independent pharmacy
      respondents identified the pharmacist pair with business formal attire and white
      coat as more approachable. Differences in education was also apparent with 70% of
      respondents in the independent pharmacy setting reporting having a Bachelor's
      degree or higher compared to 45% of respondents in the chain pharmacy setting.
      CONCLUSIONS: With the exception of approachability, patients indicated preference
      for pharmacist with the white coat regardless of community setting. Given the
      importance of patient-pharmacist communication for building successful patient
      pharmacist relationships, if patients do not perceive the pharmacists as
      approachable, communication and subsequent development of said relationships may
      not occur regardless of perceived knowledge and competency.

PMID- 24688610
TI  - Medication adherence and glycemic control in patients with psychotic disorders in
      the Veterans Affairs healthcare system.
AB  - OBJECTIVE: To compare antihyperglycemic medication adherence and glycemic control
      between individuals with schizophrenia and related psychotic disorders and a
      nonpsychiatric comparison group. METHODS: This was a retrospective medical record
      review. A total of 124 subjects with diabetes (62 patients with schizophrenia or
      a related psychotic disorder and 62 randomly selected, age-matched patients
      without a psychiatric illness) receiving their medical and psychiatric care
      exclusively through the Kansas City Veterans Affairs healthcare system during
      2008 were included in the study. Adherence to antihyperglycemic and antipsychotic
      medication was determined by refill records obtained through the computerized
      patient record system to calculate the cumulative mean gap ratio. Hemoglobin A1C
      values were utilized to compare glycemic control between groups and compared to
      glycemic goals established by diabetes treatment guidelines. RESULTS:
      Antihyperglycemic medication adherence was poor for both groups as approximately
      60% of the psychotic disorder group and 75% of the nonpsychiatric comparison
      group were without antihyperglycemic medication for greater than 30 days during
      the 12-month period but adherence did not differ between the groups (p=0.182).
      Antipsychotic adherent subjects (>=80% adherent) were more likely to be adherent
      to their antihyperglycemic medication (p=0.0003). There were no significant
      differences between groups in glycemic control. CONCLUSIONS: Antihyperglycemic
      medication adherence and glycemic control was less than optimal for both groups.
      There were no significant differences in antihyperglycemic medication adherence
      and glycemic control between patients with a psychotic disorder and those without
      a psychiatric illness.

PMID- 24688612
TI  - Medication adherence among ambulatory patients with type 2 diabetes in a tertiary
      healthcare setting in southwestern Nigeria.
AB  - OBJECTIVE: To assess adherence to medication among ambulatory patients with type
      2 diabetes, ascertain the level of glycemic control, and evaluate patients'
      opinions on probable reasons for non-adherence with a view to identify areas of
      intervention to improve adherence. METHODS: A prospective cross-sectional study
      was carried out at a 900-bed tertiary teaching hospital in Ibadan, Southwestern
      Nigeria between June and August, 2009. Out of 140 consented patients, 114 (81.4%)
      properly responded to the validated and pre-tested data collection tool and these
      were subsequently considered for analysis. Descriptive statistics were used to
      summarize the data. Means and proportions were compared using student t-test and
      chi-square or Kruskal-Wallis test as appropriate, with p<0.05 considered
      statistical significant. RESULTS: Approximately sixty percent of the patients
      were adjudged adherent with prescribed medication. Out of 58.8% of the cohort who
      gave their recent fasting plasma glucose (FPG) values, 59.7% had FPG above
      110mg/dL. The mean FPG for patients was 139.05 (SD=70.5)mg/dL, males and females
      significantly differed in their mean FPG, 146.55 (SD=85.0)mg/dL versus 133.33
      (SD=57.6)mg/dL respectively (p=0.032). Also, the mean FPG values for adherent
      patients, 137.09 (SD=59.3)mg/dL was lower than their non-adherent counterparts,
      143.92 (SD=87.6) mg/dL, but the difference was not statistically significant
      (p=0.095). Financial constraint (34.4%) was the major barrier to optimal
      adherence with medication. A significant association exist between genders and
      opinions on physician's mode of approach during patient-physician interaction as
      a contributory factor for non-adherence (p=0.038). CONCLUSIONS: Medication
      adherence of ambulatory type 2 diabetes patients is considerable. However, the
      relatively high level of adherence did not appear to have significantly impacted
      on patients' glycemic status due to a substantial number who had plasma glucose
      above the recommended targets. Multiple methods may be required to detect patient
      who report adherence but who may in fact be non-adherent. Also, adherence to
      other aspects of diabetes management plan needs to be encouraged in order to
      accomplish optimal glycemic control. Initiatives targeting patient-specific
      intervention to improve medication adherence should be considered.

PMID- 24688613
TI  - Index of learning styles in a u.s. School of pharmacy.
AB  - OBJECTIVE: The goal of this study was to assess for a predominance of learning
      styles among pharmacy students at an accredited U.S. school of pharmacy. METHODS:
      Following approval by the Institutional Review Board, the Index of Learning
      Styles(c) was administered to 210 pharmacy students. The survey provides results
      within 4 domains: perception, input, processing, and understanding. Analyses were
      conducted to determine trends in student learning styles. RESULTS: Within the
      four domains, 84% of students showed a preference toward sensory perception, 66%
      toward visual input, and 74% toward sequential understanding. Students showed no
      significant preference for active or reflective processing. Preferences were of
      moderate strength for the sensing, visual, and sequential learning styles.
      CONCLUSIONS: Students showed preferences for sensing, visual, and sequential
      learning styles with gender playing a role in learning style preferences. Faculty
      should be aware, despite some preferences, a mix of learning styles exists. To
      focus on the preferences found, instructors should focus teaching in a logical
      progression while adding visual aids. To account for other types of learning
      styles found, the instructors can offer other approaches and provide supplemental
      activities for those who would benefit from them. Further research is necessary
      to compare these learning styles to the teaching styles of pharmacy preceptors
      and faculty at schools of pharmacy.

PMID- 24688614
TI  - Detecting pre-diabetes and the role of the pharmacist.
AB  - OBJECTIVE: This study aims to use a pharmacoepidemiological approach to study the
      drug use of patients during the year prior to diabetes diagnosis (i.e. pre
      diabetic patients) and control patients. Drug use might reveal cardiovascular,
      metabolic and/or endocrinological changes and help to identify indicators for
      active monitoring of Type 2 diabetes mellitus. METHODS: A retrospective case
      control study compared drug use of patients with a future diagnosis of diabetes
      (experimental patients) with patients without a diabetes diagnosis (control
      patients) based on community pharmacy records. An experimental patient had used
      oral hypoglycaemic drugs during 2005 or 2006. Experimental and control patients
      were matched in terms of age, gender and quarter of index date. Drugs were
      selected based on possible co-morbidities of diabetes. Drug use was expressed as
      a binary variable, indicating whether or not a patient took specific drugs. Drug
      use was compared between experimental patients during the year prior to diagnosis
      and control patients using the chi-squared test. RESULTS: Our dataset covered
      5,064 patients (1,688 experimental and 3,376 control patients). A higher
      probability of taking cardiovascular drugs was observed for specific subgroups of
      patients with pre-diabetes as compared to control patients: this trend was
      observed for men as well as for women, for various cardiovascular drug classes,
      and for different age groups (p<0.05), although it was not always statistically
      significant for the 29-38 age group. For each selected age and gender group,
      patients with pre-diabetes had a higher probability of taking a combination of a
      lipid-modifying agent and an antihypertensive drug than control patients
      (p<0.005). CONCLUSIONS: Using community pharmacy data, this study demonstrated
      that age and a characteristic drug use pattern could contribute to detecting pre
      diabetes. There is a potential role for community pharmacists to follow up drug
      indicators of patients with a view to refer high-risk people for screening by a
      physician.

PMID- 24688615
TI  - Qualification, knowledge and experience of dispensers working at community
      pharmacies in Pakistan.
AB  - Pharmacies are managed by a variety of dispensers in terms of qualification,
      knowledge and experience in Pakistan. OBJECTIVE: The study aimed to document the
      state of knowledge, experience and qualification of dispensers working at
      community pharmacies in Pakistan. METHODS: A comparative cross sectional study
      was conducted at a randomly selected sample of 371 pharmacies in the three cities
      of Pakistan. A structured questionnaire for data collection was developed and
      finalized by focused group discussions and pilot testing. The data was coded,
      entered and analyzed by using SPSS Version 16. Kruskal-Wallis and Mann-Whitney
      tests (p<=0.05) were performed to find out differences. RESULTS: Out of total
      sample of 371 pharmacies, 31.8 % (118) were in Islamabad, 32.4 % (120) in
      Peshawar and 35.8 % (133) were in Lahore. Fifty percent of the respondents had
      correct knowledge of range of room temperature at which medicines should be
      stored. Only 11.1% (41) of the respondents knew about OTC (over the counter
      drugs) which can be sold without prescription while 5.9 % (22) of the respondents
      were aware of POM (prescription only medicines) which can be only sold on a valid
      prescription. While 87.6% (325), 88.1% (327), 58.7% (318) and 95.7 % (355) of the
      respondents did not know the meaning of the dispensing abbreviations such as
      'h.s', 'q.d', 'sos' and 'p.r.n'. The respondents did not know correctly the
      status of Deltacortil(r) (Prednisolone), Septran(r) (Sulfamethoxazole) and
      Fansidar(r) (Pyrimethamine and Sulfadoxine) either as OTC or POM in 26.7% (99),
      64.2% (238), and 44.5 % (165) of the cases, respectively. There was a significant
      difference (p<=0.05) in knowledge of dispensers regarding storage temperature,
      prescription terminologies and status of medicines having different level of
      qualification and experience. CONCLUSIONS: The overall knowledge and training of
      dispensers working at community pharmacies is inadequate in Pakistan. However,
      pharmacists had relatively better knowledge regarding storage temperature,
      prescription terminologies and status of medicines as compared to pharmacy
      assistants, diploma holders and salesperson.

PMID- 24688616
TI  - A pre- post-evaluation of implementing an inpatient warfarin monitoring and
      education program.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether a new
      anticoagulation management program resulted in better monitoring of warfarin,
      increased warfarin patient education prior to discharge, and fewer bleeding
      complications associated with warfarin. METHODS: A retrospective chart review was
      conducted of patients who were inpatients and received warfarin from April 1,
      2008 to July 31, 2008 (control group) and from April 1, 2009 to July 31, 2009
      (after implementation of the new anticoagulation program). The frequency of
      warfarin-related laboratory orders that included international normalized ratios
      (INRs), complete blood counts (CBCs), and documented patient education by
      pharmacy, nursing, and dietary services were determined before and after program
      implementation. Also, data was collected to determine frequencies of bleeding
      complications associated with warfarin. RESULTS: There were 112 patients in the
      pre- and 115 patients in the post-program group. After implementation of the
      inpatient warfarin management program, obtaining baseline INRs increased from 74%
      to 90% (p=0.001). Orders for baseline CBCs increased from 85% to 94% (p=0.026).
      Obtaining CBCs every 3 days increased from 54% to 74%, (p<0.001). However, there
      was no significant change in orders for daily INRs (p=0.055). Education by
      nursing increased from 54% to 80%, (p<0.001), by pharmacy increased from 8% to
      76%, (p<0.001), and by dietary increased from 11% to 79%, (p<0.001).
      Documentation by all three disciplines in each patient increased from 3.6% to
      59%, (p<0.001). Significantly fewer patients received vitamin K and/ or fresh
      frozen plasma for supratherapeutic INRs with bleeding complications after the
      program was initiated compared to baseline (p=0.009). CONCLUSIONS: The
      implementation of an inpatient warfarin management program led to better
      monitoring of patients receiving warfarin, and increased patient education.
      However, a larger and longer assessment is necessary to determine if these
      changes are maintained and how these changes affect long-term clinical outcomes.

PMID- 24688617
TI  - Pharmacy intervention on antimicrobial management of critically ill patients.
AB  - Frequent, suboptimal use of antimicrobial drugs has resulted in the emergence of
      microbial resistance, compromised clinical outcomes and increased costs,
      particularly in the intensive care unit (ICU). Mounting on these challenges is
      the paucity of new antimicrobial agents. OBJECTIVE: The study aims to determine
      the impact of prospective pharmacy-driven antimicrobial stewardship in the ICU on
      clinical and potential financial outcomes. The primary objectives were to
      determine the mean length of stay (LOS) and mortality rate in the ICU resulting
      from prospective pharmacy interventions on antimicrobial therapy. The secondary
      objective was to calculate the difference in total drug acquisition costs
      resulting from pharmacy infectious diseases (ID)-related interventions. METHODS:
      In collaboration with an infectious disease physician, the ICU pharmacy team
      provided prospective audit with feedback to physicians on antimicrobial therapies
      of 70 patients over a 4-month period in a 31-bed ICU. In comparison with
      published data, LOS and mortality of pharmacy-monitored ICU patients were
      recorded. Daily cost savings on antimicrobial drugs and charges for medication
      therapy management (MTM) services were added to calculate potential total cost
      savings. Pharmacy interventions focused on streamlining, dose optimization,
      intravenous-to-oral conversion, antimicrobial discontinuation, new recommendation
      and drug information consult. Antimicrobial education was featured in oral
      presentations and electronic newsletters for pharmacists and clinicians. RESULTS:
      The mean LOS in the ICU was 6 days, which was lower than the published reports of
      LOS ranging from 11 to 36 days. The morality rate of 14% was comparable to the
      reported range of 6 to 20% in published literature. The total drug cost
      difference was a negative financial outcome or loss of USD192 associated with ID
      related interventions. CONCLUSIONS: In collaboration with the infectious disease
      physician, prospective pharmacy intervention on antimicrobial therapy in the ICU
      led to positive clinical outcomes and an additional drug cost expense of USD192.

PMID- 24688618
TI  - The impact of pharmaceutical care on patients with hypertension and their
      pharmacists.
AB  - OBJECTIVE: The purpose of the study was to assess the influence of pharmaceutical
      care on patients' knowledge, quality of life and blood pressure and to determine
      whether new type of pharmaceutical services changes the pharmacists' satisfaction
      and knowledge. METHODS: Community pharmacies were randomly assigned to study and
      control group and pharmacists from both groups included patients with
      hypertension, who meet inclusion and exclusion criteria. Study group provided the
      pharmaceutical care (education, pharmacotherapy monitoring, detecting and solving
      drug related problems) for their patients, while the control group provided the
      standard pharmaceutical services (dispensing medicines with or without
      counseling). At the beginning and the end of the study pharmacists and patients
      filled in the knowledge test. Pharmacists fulfilled also satisfaction
      questionnaire. RESULTS: Survey data were collected from 28 and 56 patients from
      community pharmacies in study and control group respectively. At the last meeting
      the normal blood pressure achieved 79% and 55% patients in study and control
      group, respectively (p>0,05). The pharmaceutical care improved patients'
      knowledge about disease. Pharmacists from study group, who provided
      pharmaceutical care, had higher level of pharmacotherapy knowledge and
      professional satisfaction than the control group. CONCLUSIONS: Implementation of
      pharmaceutical care into the pharmacy practice benefits both, patients and
      pharmacists.

PMID- 24688619
TI  - The role of ultrasonography in the diagnosis of rheumatoid arthritis and
      peripheral spondyloarthropathies.
AB  - In recent years a dynamic development of ultrasound technology has been observed.
      Consequently, ultrasound is increasingly being utilized in rheumatology. With the
      introduction of high-frequency (up to 18 MHz) linear probes, sensitive Doppler
      techniques, harmonic imaging options and cross beams, ultrasound is used in the
      initial diagnosis of rheumatic diseases, monitoring of the effectiveness of
      treatment and confirmation of remission. Ultrasound cannot identify specific
      rheumatic diseases, but it does allow for an evaluation of the type of pathology,
      including an assessment of disease progression and its location. These
      irregularities include: synovial pathologies, effusion, tendon, cartilage and
      bone lesions, tendon and ligament pathology at the site of their insertion
      (enthesopathies). This publication discusses the wide spectrum of changes in
      peripheral joints and entheses observed on ultrasound. Special consideration is
      given to the ultrasound, which besides an MRI is a leading diagnostic tool in the
      diagnosis of early stages of the disease and monitoring of disease progression. 

PMID- 24688620
TI  - The use of isotretinoin in the treatment of acne vulgaris: clinical
      considerations and future directions.

PMID- 24688621
TI  - Polypodium leucotomos as an Adjunct Treatment of Pigmentary Disorders.
AB  - INTRODUCTION: Extracts of the tropical fern Polypodium leucotomos appear to
      possess beneficial properties for the skin attributed to the presence of numerous
      compounds within the extract that have antioxidant and photoprotective
      properties. Orally administered Polypodium leucotomos may provide protection
      against the detrimental photoaging effects of sunlight and can also help reduce
      the frequency and severity of polymorphous light eruption. Polypodium leucotomos
      has also been shown to be beneficial for the prevention and potential treatment
      of several aesthetically relevant conditions. OBJECTIVE: The purpose of this
      review is to investigate the beneficial role of Polypodium leucotomos as an
      adjunct treatment for vitiligo, melasma, and postinflammatory hyperpigmentation.
      RESULTS: Based on a review of relevant literature including the results of a
      randomized, placebo-controlled study, the oral administration of Polypodium
      leucotomos significantly improved the severity of melasma in women after 12
      weeks. Three randomized, double-blind, placebo-controlled studies have
      demonstrated significant improvements in vitiligo when oral Polypodium leucotomos
      therapy was combined with psoralens plus ultraviolet A and narrowband ultraviolet
      B. No controlled studies have assessed the efficacy of Polypodium leucotomos for
      the treatment of postinflammatory hyperpigmentation; however, its known
      antioxidant and anti-inflammatory properties and demonstrated effectiveness for
      melasma support its use for treating this condition. No adverse events have been
      associated with the use of Polypodium leucotomos. CONCLUSION: In addition to
      preventing many harmful effects associated with sunlight exposure, orally
      administered Polypodium leucotomos also appears to provide adjunctive benefits in
      treating vitiligo, melasma, and may have the potential to help with
      postinflammatory hyperpigmentation.

PMID- 24688623
TI  - Efficacy of a New Topical Nano-hyaluronic Acid in Humans.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of a new topical
      low molecular nano-hyaluronic acid preparation in treating wrinkles, skin
      hydration, and skin elasticity in humans. METHODS: Thirty-three women with an
      average age of 45.2 were studied for a period of eight weeks to measure the anti
      wrinkle efficacy of a new nano-hyaluronic acid. The measurements were performed
      in the periorbital regions by investigating the three-dimensional structure using
      a DermaTOP for wrinkles, Corneometer for skin hydration, Cutometer for skin
      elasticity, and a Chroma Meter for erythema. Thereafter, standardized images were
      taken and evaluated by six selected and trained raters at the end of the study
      for reduction of visible wrinkles as well as skin color uniformity and
      pigmentation. RESULTS: The results of the study showed a statistically
      significant moisturizing effect of the product range (lotion, serum, and cream,
      after 2,4, and 8 weeks of treatment. Measurement of skin roughness showed a
      significantly finer skin structure after two weeks of treatment, and skin
      elasticity showed a significant improvement after 2 and 8 weeks of treatment.
      CONCLUSION: The new nano-hyaluronic acid clearly demonstrated a significant
      benefit in decreasing the depth of wrinkles (up to 40%), and skin hydration (up
      to 96%) and skin firmness and elasticity were significantly enhanced (up to 55%)
      at the end of eight weeks.

PMID- 24688622
TI  - Moisturizers and Ceramide-containing Moisturizers May Offer Concomitant Therapy
      with Benefits.
AB  - INTRODUCTION: Ceramide-containing moisturizers may offer benefits as an adjunct
      to acne treatment. METHODS: An expert panel of 11 Canadian dermatologists,
      including an international clinical scientist, used the following modified Delphi
      process: 1) A systematic literature review for acne treatment, dry skin,
      irritation, depletion of ceramides in acne, and benefits of moisturizers and
      ceramide-containing moisturizers was conducted; 2) panel members gave their
      opinion on the resulting statements, taking into account their treatment
      practices; 3) a panel meeting was held during the 2011 Canadian Dermatology
      Update to determine final statements; 4) the panel reviewed the final document.
      RESULTS: The panel reached the following consensus (11/11): 1) A very important
      reason for nonadherence to acne treatment is dry skin and irritation; 2) skin
      barrier dysfunction may contribute to acne; 3) dry skin and irritation commonly
      results from topical acne treatment; 4) dry skin and irritation commonly results
      from systemic retinoid therapy; 5) moisturizers can improve dryness and
      irritation resulting from acne treatment; 6) ceramide-containing moisturizers may
      enhance adherence and complement existing acne therapies; 7) adjunctive therapy
      with moisturizers should be considered in acne-treated patients. CONCLUSION: The
      panel proposes that adjunctive therapy with moisturizers, particularly ceramide
      containing moisturizers, should be considered in acne-treated patients.

PMID- 24688624
TI  - Diet and dermatitis: food triggers.
AB  - Given increasing awareness of the link between diet and health, many patients are
      concerned that dietary factors may trigger dermatitis. Research has found that
      dietary factors can indeed exacerbate atopic dermatitis or cause dermatitis due
      to systemic contact dermatitis. In atopic dermatitis, dietary factors are more
      likely to cause an exacerbation among infants or children with moderate-to-severe
      atopic dermatitis relative to other populations. Foods may trigger rapid,
      immunoglobulin E-mediated hypersensitivity reactions or may lead to late
      eczematous reactions. While immediate reactions occur within minutes to hours of
      food exposure, late eczematous reactions may occur anywhere from hours to two
      days later. Screening methods, such as food allergen-specific serum
      immunoglobulin E tests or skin prick tests, can identify sensitization to
      specific foods, but a diagnosis of food allergy requires specific signs and
      symptoms that occur reproducibly upon food exposure. Many patients who are
      sensitized will not develop clinical findings upon food exposure; therefore,
      these tests may result in false-positive tests for food allergy. This is why the
      gold standard for diagnosis remains the double-blind, placebo-controlled food
      challenge. In another condition, systemic contact dermatitis, ingestion of a
      specific food can actually cause dermatitis. Systemic contact dermatitis is a
      distinct T-cell mediated immunological reaction in which dietary exposure to
      specific allergens results in dermatitis. Balsam of Peru and nickel are well
      known causes of systemic contact dermatitis, and reports have implicated multiple
      other allergens. This review seeks to increase awareness of important food
      allergens, elucidate their relationship with atopic dermatitis and systemic
      contact dermatitis, and review available diagnostic and treatment strategies. 

PMID- 24688626
TI  - Refractory Postinflammatory Hyperpigmentation Treated Fractional CO2 Laser.
AB  - OBJECTIVE: Postinflammatory hyperpigmentation is a reactive hypermelanosis of the
      skin that occurs as a consequence of an inflammatory process, such as acne,
      eczema, drug reactions, burns, chemical peelings, and laser applications.
      Although topical agents remain to be the first-line treatment of postinflammatory
      hyperpigmentation, treatment of recalcitrant cases is challenging. The Q-switched
      ruby laser, the low-dose Q-switched neodymium-doped yttrium aluminum garnet
      laser, and the fractional 1550nm erbium-doped fiber laser have been reported to
      improve postinflammatory hyperpigmentation. DESIGN/SETTING/PARTICIPANTS: The
      authors present a case of refractory postinflammatory hyperpigmentation
      successfully treated with two sessions of fractional CO2 laser in a 24-year-old
      woman with Fitzpatrick skin type III. RESULTS: After two treatment sessions with
      a one-month interval, the lesion totally cleared without any complications.
      CONCLUSION: Although many laser systems, including fractional CO2 lasers, can
      cause postinflammatory hyperpigmentation, they also can be very efficacious tools
      by using conservative laser settings and by providing appropriate post-treatment
      care in recalcitrant postinflammatory hyperpigmentation treatment.

PMID- 24688625
TI  - Malassezia (pityrosporum) folliculitis.
AB  - Malassezia (Pityrosporum) folliculitis is a fungal acneiform condition commonly
      misdiagnosed as acne vulgaris. Although often associated with common acne, this
      condition may persist for years without complete resolution with typical acne
      medications. Malassezia folliculitis results from overgrowth of yeast present in
      the normal cutaneous flora. Eruptions may be associated with conditions altering
      this flora, such as immunosuppression and antibiotic use. The most common
      presentation is monomorphic papules and pustules, often on the chest, back,
      posterior arms, and face. Oral antifungals are the most effective treatment and
      result in rapid improvement. The association with acne vulgaris may require
      combinations of both antifungal and acne medications. This article reviews and
      updates readers on this not uncommon, but easily missed, condition. 

PMID- 24688627
TI  - Mohs Surgery in Patients Immunobullous Diseases: Should Prednisone be Increased
      Prior to Surgery?
AB  - BACKGROUND: Mohs surgery is one of the most effective treatment options for skin
      cancers as it offers one of the highest chances for cure. Mohs surgery is a
      precise technique that removes a layer at a time. Although this may be
      advantageous, this treatment method is difficult in patients with immunobullous
      diseases. Currently the guidelines for Mohs surgery do not discuss the
      premanagement of immunobullous patients about to undergo Mohs surgery. OBJECTIVE:
      To advocate for increasing prednisone dose in patients with immunobullous disease
      prior to undergoing Mohs surgery. CASE REPORT: The authors present a case of an
      excision of a squamous cell carcinoma from a 94-year-old woman with a history of
      pemphigus vulgaris using Mohs micrographic surgery. CONCLUSION: Current
      preoperative guidelines for Mohs surgery do not address the issue of altering
      steroid medications for patients with immunobullous disease prior to the
      procedure. The authors suggest that patients with a history of immunobullous
      disease undergoing Mohs micrographic surgery should have an increase in steroid
      dose prior to surgery.

PMID- 24688628
TI  - Assessing Myocardial Disease Using T1rho MRI.
AB  - There is great interest to use magnetic resonance imaging (MRI) for non-invasive
      assessment of myocardial disease in ischemic and non-ischemic cardiomyopathies.
      Recently, there has been a renewed interest to use a magnetic resonance imaging
      (MRI) technique utilizing spin locking radiofrequency (RF) pulses, called T1rho
      MRI. The spin locking RF pulse creates sensitivity to some mechanisms of nuclear
      relaxation such as 1H exchange between water and amide, amine and hydroxyl
      functional groups in molecules; consequently, there is the potential to non
      invasively, and without exogenous contrast agents, obtain important molecular
      information from diseased myocardial tissue. The purpose of this article is to
      review and critically examine the recent published literature in the field
      related to T1rho MRI of myocardial disease.

PMID- 24688631
TI  - Announcing Computational and Structural Biotechnology Journal: not just another
      open-access journal.

PMID- 24688629
TI  - Oxidative stress in aging: advances in proteomic approaches.
AB  - Aging is a gradual, complex process in which cells, tissues, organs, and the
      whole organism itself deteriorate in a progressive and irreversible manner that,
      in the majority of cases, implies pathological conditions that affect the
      individual's Quality of Life (QOL). Although extensive research efforts in recent
      years have been made, the anticipation of aging and prophylactic or treatment
      strategies continue to experience major limitations. In this review, the focus is
      essentially on the compilation of the advances generated by cellular expression
      profile analysis through proteomics studies (two-dimensional [2D] electrophoresis
      and mass spectrometry [MS]), which are currently used as an integral approach to
      study the aging process. Additionally, the relevance of the oxidative stress
      factors is discussed. Emphasis is placed on postmitotic tissues, such as
      neuronal, muscular, and red blood cells, which appear to be those most frequently
      studied with respect to aging. Additionally, models for the study of aging are
      discussed in a number of organisms, such as Caenorhabditis elegans, senescence
      accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the
      beagle canine. Proteomic studies in specific tissues and organisms have revealed
      the extensive involvement of reactive oxygen species (ROS) and oxidative stress
      in aging. 

PMID- 24688630
TI  - Oxidative stress is predominant in female but not in male patients with
      autoimmune thrombocytopenia.
AB  - As the involvement of oxidative stress (OS) in autoimmune thrombocytopenia (AITP)
      has been reported, a fast and rapid test for the reliable measurement of OS and
      antioxidant capacities (AOCs) might be a useful tool in extending current
      diagnostic possibilities. The free oxygen radical test (FORT) and free oxygen
      radical defence (FORD) assay (Callegari, Italy) are easy to perform and reliable,
      with results available within 15 minutes. Thirty-seven AITP patients and 37
      matched healthy individuals were included in this study. All participants
      responded to a standard questionnaire provided by these assays. Female patients
      with AITP were observed to demonstrate significantly higher OS in comparison to
      female controls (P = 0.0027) and male AITP patients (P = 0.0018). The AOCs were
      not reduced in patients with AITP (P = 0.7648). Correlation of OS with platelet
      count identified a weak positive correlation (P = 0.0327, Spearman R = 0.4672).
      The questionnaire revealed that ITP patients in comparison to healthy controls
      are more stressed, feel exhausted and fatigued, and eat a healthier diet. In
      conclusion, OS is predominant in female but not in male patients with AITP
      suggesting gender-specific differences in the pathomechanisms of AITP.
      Identification of patients with high levels of OS might be beneficial in the
      management of AITP. 

PMID- 24688632
TI  - Mathematical and Computational Modelling of Ribosomal Movement and Protein
      Synthesis: an overview.
AB  - Translation or protein synthesis consists of a complex system of chemical
      reactions, which ultimately result in decoding of the mRNA and the production of
      a protein. The complexity of this reaction system makes it difficult to
      quantitatively connect its input parameters (such as translation factor or
      ribosome concentrations, codon composition of the mRNA, or energy availability)
      to output parameters (such as protein synthesis rates or ribosome densities on
      mRNAs). Mathematical and computational models of translation have now been used
      for nearly five decades to investigate translation, and to shed light on the
      relationship between the different reactions in the system. This review gives an
      overview over the principal approaches used in the modelling efforts, and
      summarises some of the major findings that were made. 

PMID- 24688633
TI  - Capturing RNA-dependent pathways for cryo-EM analysis.
AB  - Cryo-Electron Microscopy (EM) is a powerful technique to visualize biological
      processes at nanometer resolution. Structural studies of macromolecular
      assemblies are typically performed on individual complexes that are biochemically
      isolated from their cellular context. Here we present a molecular imaging
      platform to capture and view multiple components of cellular pathways within a
      functionally relevant framework. We utilized the bacterial protein synthesis
      machinery as a model system to develop our approach. By using modified Affinity
      Grid surfaces, we were able to recruit multiple protein assemblies bound to
      nascent strands of mRNA. The combined use of Affinity Capture technology and
      single particle electron microscopy provide the basis for visualizing RNA
      dependent pathways in a remarkable new way. 

PMID- 24688634
TI  - The use of hammett constants to understand the non-covalent binding of aromatics.
AB  - Non-covalent interactions of aromatics are important in a wide range of chemical
      and biological applications. The past two decades have seen numerous reports of
      arene-arene binding being understood in terms Hammett substituent constants, and
      similar analyses have recently been extended to cation-arene and anion-arene
      binding. It is not immediately clear why electrostatic Hammett parameters should
      work so well in predicting the binding for all three interactions, given that
      different intermolecular forces dominate each interaction. This review explores
      such anomalies, and summarizes how Hammett substituent constants have been
      employed to understand the non-covalent binding in arene-arene, cation-arene and
      anion-arene interactions. 

PMID- 24688635
TI  - Genetic code redundancy and its influence on the encoded polypeptides.
AB  - The genetic code is said to be redundant in that the same amino acid residue can
      be encoded by multiple, so-called synonymous, codons. If all properties of
      synonymous codons were entirely equivalent, one would expect that they would be
      equally distributed along protein coding sequences. However, many studies over
      the last three decades have demonstrated that their distribution is not entirely
      random. It has been postulated that certain codons may be translated by the
      ribosome faster than others and thus their non-random distribution dictates how
      fast the ribosome moves along particular segments of the mRNA. The reasons behind
      such segmental variability in the rates of protein synthesis, and thus
      polypeptide emergence from the ribosome, have been explored by theoretical and
      experimental approaches. Predictions of the relative rates at which particular
      codons are translated and their impact on the nascent chain have not arrived at
      unequivocal conclusions. This is probably due, at least in part, to variation in
      the basis for classification of codons as "fast" or "slow", as well as
      variability in the number and types of genes and proteins analyzed. Recent
      methodological advances have allowed nucleotide-resolution studies of ribosome
      residency times in entire transcriptomes, which confirm the non-uniform movement
      of ribosomes along mRNAs and shed light on the actual determinants of rate
      control. Moreover, experiments have begun to emerge that systematically examine
      the influence of variations in ribosomal movement and the fate of the emerging
      polypeptide chain. 

PMID- 24688637
TI  - Thumb-loops up for catalysis: a structure/function investigation of a functional
      loop movement in a GH11 xylanase.
AB  - Dynamics is a key feature of enzyme catalysis. Unfortunately, current
      experimental and computational techniques do not yet provide a comprehensive
      understanding and description of functional macromolecular motions. In this work,
      we have extended a novel computational technique, which combines molecular
      modeling methods and robotics algorithms, to investigate functional motions of
      protein loops. This new approach has been applied to study the functional
      importance of the so-called thumb-loop in the glycoside hydrolase family 11
      xylanase from Thermobacillus xylanilyticus (Tx-xyl). The results obtained provide
      new insight into the role of the loop in the glycosylation/deglycosylation
      catalytic cycle, and underline the key importance of the nature of the residue
      located at the tip of the thumb-loop. The effect of mutations predicted in silico
      has been validated by in vitro site-directed mutagenesis experiments. Overall, we
      propose a comprehensive model of Tx-xyl catalysis in terms of substrate and
      product dynamics by identifying the action of the thumb-loop motion during
      catalysis. 

PMID- 24688638
TI  - Limiting factors in single particle cryo electron tomography.
AB  - Modern methods of cryo electron microscopy and tomography allow visualization of
      protein nanomachines in their native state at the nanometer scale. Image
      processing methods including sub-volume averaging applied to repeating
      macromolecular elements within tomograms allow exploring their structures within
      the native context of the cell, avoiding the need for protein isolation and
      purification. Today, many different data acquisition protocols and software
      solutions are available to researchers to determine average structures of
      macromolecular complexes and potentially to classify structural intermediates.
      Here, we list the density maps reported in the literature, and analyze each
      structure for the chosen instrumental settings, sample conditions, main
      processing steps, and obtained resolution. We present conclusions that identify
      factors currently limiting the resolution gained by this approach. 

PMID- 24688636
TI  - Structural biology of the intrinsic cell death pathway: what do we know and what
      is missing?

PMID- 24688639
TI  - Integration of QSAR and SAR methods for the mechanistic interpretation of
      predictive models for carcinogenicity.
AB  - The knowledge-based Toxtree expert system (SAR approach) was integrated with the
      statistically based counter propagation artificial neural network (CP ANN) model
      (QSAR approach) to contribute to a better mechanistic understanding of a
      carcinogenicity model for non-congeneric chemicals using Dragon descriptors and
      carcinogenic potency for rats as a response. The transparency of the CP ANN
      algorithm was demonstrated using intrinsic mapping technique specifically Kohonen
      maps. Chemical structures were represented by Dragon descriptors that express the
      structural and electronic features of molecules such as their shape and
      electronic surrounding related to reactivity of molecules. It was illustrated how
      the descriptors are correlated with particular structural alerts (SAs) for
      carcinogenicity with recognized mechanistic link to carcinogenic activity.
      Moreover, the Kohonen mapping technique enables one to examine the separation of
      carcinogens and non-carcinogens (for rats) within a family of chemicals with a
      particular SA for carcinogenicity. The mechanistic interpretation of models is
      important for the evaluation of safety of chemicals. 

PMID- 24688640
TI  - Assessment of automated analyses of cell migration on flat and nanostructured
      surfaces.
AB  - Motility studies of cells often rely on computer software that analyzes time
      lapse recorded movies and establishes cell trajectories fully automatically. This
      raises the question of reproducibility of results, since different programs could
      yield significantly different results of such automated analysis. The fact that
      the segmentation routines of such programs are often challenged by nanostructured
      surfaces makes the question more pertinent. Here we illustrate how it is possible
      to track cells on bright field microscopy images with image analysis routines
      implemented in an open-source cell tracking program, PACT (Program for Automated
      Cell Tracking). We compare the automated motility analysis of three cell tracking
      programs, PACT, Autozell, and TLA, using the same movies as input for all three
      programs. We find that different programs track overlapping, but different
      subsets of cells due to different segmentation methods. Unfortunately, population
      averages based on such different cell populations, differ significantly in some
      cases. Thus, results obtained with one software package are not necessarily
      reproducible by other software. 

PMID- 24688641
TI  - In silico evidence of signaling pathways of notch mediated networks in leukemia.
AB  - Notch signaling plays a critical role in cell fate determination and maintenance
      of progenitors in many developmental systems. Notch receptors have been shown to
      be expressed on hematopoietic progenitor cells as well as to various degrees in
      peripheral blood T and B lymphocytes, monocytes, and neutrophils. Our aim was to
      understand the protein interaction network, using Notch1 protein name as query in
      STRING database and we generated a model to assess the significance of Notch1
      associated proteins in Acute Lymphoblastic Leukemia (ALL). We further analyzed
      the expression levels of the genes encoding hub proteins, using Oncomine
      database, to determine their significance in leukemogenesis. Of the forty two hub
      genes, we observed that sixteen genes were underexpressed and eleven genes were
      overexpressed in T-cell Acute Lymphoblastic samples in comparison to their
      expression levels in normal cells. Of these, we found three novel genes which
      have not been reported earlier- KAT2B, PSEN1 (underexpressed) and CDH2
      (overexpressed).These three identified genes may provide new insights into the
      abnormal hematopoietic process observed in Leukemia as these genes are involved
      in Notch signaling and cell adhesion processes. It is evident that experimental
      validation of the protein interactors in leukemic cells could help in the
      identification of new diagnostic markers for leukemia. 

PMID- 24688642
TI  - Editorial note: advances in enzymology and enzyme engineering.

PMID- 24688644
TI  - Rational approaches for engineering novel functionalities in carbon-carbon bond
      forming enzymes.
AB  - Enzymes that catalyze carbon-carbon bond formation can be exploited as
      biocatalyst for synthetic organic chemistry. However, natural enzymes frequently
      do not possess the required properties or specificities to catalyze industrially
      useful transformations. This mini-review describes recent work using knowledge
      guided site-specific mutagenesis of key active site residues to alter substrate
      specificity, stereospecificity and reaction specificity of these enzymes. In
      addition, examples of de novo designed enzymes that catalyze C-C bond reactions
      not found in nature will be discussed. 

PMID- 24688645
TI  - Approaches to engineer stability of beetle luciferases.
AB  - Luciferase enzymes from fireflies and other beetles have many important
      applications in molecular biology, biotechnology, analytical chemistry and
      several other areas. Many novel beetle luciferases with promising properties have
      been reported in the recent years. However, actual and potential applications of
      wild-type beetle luciferases are often limited by insufficient stability or
      decrease in activity of the enzyme at the conditions of a particular assay.
      Various examples of genetic engineering of the enhanced beetle luciferases have
      been reported that successfully solve or alleviate many of these limitations.
      This mini-review summarizes the recent advances in development of mutant
      luciferases with improved stability and activity characteristics. It discusses
      the common limitations of wild-type luciferases in different applications and
      presents the efficient approaches that can be used to address these problems. 

PMID- 24688643
TI  - Computational approaches for rational design of proteins with novel
      functionalities.
AB  - Proteins are the most multifaceted macromolecules in living systems and have
      various important functions, including structural, catalytic, sensory, and
      regulatory functions. Rational design of enzymes is a great challenge to our
      understanding of protein structure and physical chemistry and has numerous
      potential applications. Protein design algorithms have been applied to design or
      engineer proteins that fold, fold faster, catalyze, catalyze faster, signal, and
      adopt preferred conformational states. The field of de novo protein design,
      although only a few decades old, is beginning to produce exciting results.
      Developments in this field are already having a significant impact on
      biotechnology and chemical biology. The application of powerful computational
      methods for functional protein designing has recently succeeded at engineering
      target activities. Here, we review recently reported de novo functional proteins
      that were developed using various protein design approaches, including rational
      design, computational optimization, and selection from combinatorial libraries,
      highlighting recent advances and successes. 

PMID- 24688646
TI  - Lipase improvement: goals and strategies.

PMID- 24688647
TI  - Structural and mechanistic fundamentals for designing of cellulases.

PMID- 24688648
TI  - Computational enzyme design approaches with significant biological outcomes:
      progress and challenges.
AB  - Enzymes are powerful biocatalysts, however, so far there is still a large gap
      between the number of enzyme-based practical applications and that of naturally
      occurring enzymes. Multiple experimental approaches have been applied to generate
      nearly all possible mutations of target enzymes, allowing the identification of
      desirable variants with improved properties to meet the practical needs.
      Meanwhile, an increasing number of computational methods have been developed to
      assist in the modification of enzymes during the past few decades. With the
      development of bioinformatic algorithms, computational approaches are now able to
      provide more precise guidance for enzyme engineering and make it more efficient
      and less laborious. In this review, we summarize the recent advances of method
      development with significant biological outcomes to provide important insights
      into successful computational protein designs. We also discuss the limitations
      and challenges of existing methods and the future directions that should improve
      them. 

PMID- 24688650
TI  - Computational Enzyme Design: Advances, hurdles and possible ways forward.
AB  - This mini review addresses recent developments in computational enzyme design.
      Successful protocols as well as known issues and limitations are discussed from
      an energetic perspective. It will be argued that improved results can be obtained
      by including a dynamic treatment in the design protocol. Finally, a molecular
      dynamics-based approach for evaluating and refining computational designs is
      presented. 

PMID- 24688649
TI  - Computer-Aided Protein Directed Evolution: a Review of Web Servers, Databases and
      other Computational Tools for Protein Engineering.
AB  - The combination of computational and directed evolution methods has proven a
      winning strategy for protein engineering. We refer to this approach as computer
      aided protein directed evolution (CAPDE) and the review summarizes the recent
      developments in this rapidly growing field. We will restrict ourselves to
      overview the availability, usability and limitations of web servers, databases
      and other computational tools proposed in the last five years. The goal of this
      review is to provide concise information about currently available computational
      resources to assist the design of directed evolution based protein engineering
      experiment. 

PMID- 24688651
TI  - Recent advances in rational approaches for enzyme engineering.
AB  - Enzymes are an attractive alternative in the asymmetric syntheses of chiral
      building blocks. To meet the requirements of industrial biotechnology and to
      introduce new functionalities, the enzymes need to be optimized by protein
      engineering. This article specifically reviews rational approaches for enzyme
      engineering and de novo enzyme design involving structure-based approaches
      developed in recent years for improvement of the enzymes' performance, broadened
      substrate range, and creation of novel functionalities to obtain products with
      high added value for industrial applications. 

PMID- 24688652
TI  - Engineering non-heme mono- and dioxygenases for biocatalysis.
AB  - Oxygenases are ubiquitous enzymes that catalyze the introduction of one or two
      oxygen atoms to unreactive chemical compounds. They require reduction equivalents
      from NADH or NADPH and comprise metal ions, metal ion complexes, or coenzymes in
      their active site. Thus, for industrial purposes, oxygenases are most commonly
      employed using whole cell catalysis, to alleviate the need for co-factor
      regeneration. Biotechnological applications include bioremediation, chiral
      synthesis, biosensors, fine chemicals, biofuels, pharmaceuticals, food
      ingredients and polymers. Controlling activity and selectivity of oxygenases is
      therefore of great importance and of growing interest to the scientific
      community. This review focuses on protein engineering of non-heme monooxygenases
      and dioxygenases for generating improved or novel functionalities. Rational
      mutagenesis based on x-ray structures and sequence alignment, as well as random
      methods such as directed evolution, have been utilized. It is concluded that
      knowledge-based protein engineering accompanied with targeted libraries, is most
      efficient for the design and tuning of biocatalysts towards novel substrates and
      enhanced catalytic activity while minimizing the screening efforts. 

PMID- 24688653
TI  - Directed evolution: selection of the host organism.
AB  - Directed evolution has become a well-established tool for improving proteins and
      biological systems. A critical aspect of directed evolution is the selection of a
      suitable host organism for achieving functional expression of the target gene. To
      date, most directed evolution studies have used either Escherichia coli or
      Saccharomyces cerevisiae as a host; however, other bacterial and yeast species,
      as well as mammalian and insect cell lines, have also been successfully used.
      Recent advances in synthetic biology and genomics have opened the possibility of
      expanding the use of directed evolution to new host organisms such as microalgae.
      This review focuses on the different host organisms used in directed evolution
      and highlights some of the recent directed evolution strategies used in these
      organisms. 

PMID- 24688654
TI  - Tailor-made biocatalysts: combining thermodynamics, organic synthesis, molecular
      biology, biochemistry and microbiology for the design of enzyme selections.
AB  - A general strategy for the isolation of catalysts for given chemical reactions
      was designed. A FIRST LINK BETWEEN GENES AND THEIR CORRESPONDING PROTEINS WAS
      ESTABLISHED BY PHAGE DISPLAY: using Darwin's principles on evolution based on
      selection and amplification, rare protein molecules can then be selected for
      function from a large repertoire prior to their characterization by sequencing of
      their genes. A second link was created between enzymes and their products. By
      making use of the chelate effect and of Inovirus particles as a chemical,
      affinity chromatography for the reaction product is then sufficient to isolate
      among 10(6) to 10(11) proteins and their genes, the rare ones coding for
      catalysts of interest. The strategy for the parallel processing of information on
      the catalytic activity of variants from a large protein repertoire is highlighted
      in this review. 

PMID- 24688655
TI  - Emerging role of N- and C-terminal interactions in stabilizing (beta/alpha)8 fold
      with special emphasis on Family 10 xylanases.
AB  - Xylanases belong to an important class of industrial enzymes. Various xylanases
      have been purified and characterized from a plethora of organisms including
      bacteria, marine algae, plants, protozoans, insects, snails and crustaceans.
      Depending on the source, the enzymatic activity of xylanases varies considerably
      under various physico-chemical conditions such as temperature, pH, high salt and
      in the presence of proteases. Family 10 or glycosyl hydrolase 10 (GH10) xylanases
      are one of the well characterized and thoroughly studied classes of industrial
      enzymes. The TIM-barrel fold structure which is ubiquitous in nature is one of
      the characteristics of family 10 xylanases. Family 10 xylanases have been used as
      a "model system" due to their TIM-barrel fold to dissect and understand protein
      stability under various conditions. A better understanding of structure-stability
      function relationships of family 10 xylanases allows one to apply these governing
      molecular rules to engineer other TIM-barrel fold proteins to improve their
      stability and retain function(s) under adverse conditions. In this review, we
      discuss the implications of N-and C-terminal interactions, observed in family 10
      xylanases on protein stability under extreme conditions. The role of metal
      binding and aromatic clusters in protein stability is also discussed. Studying
      and understanding family 10 xylanase structure and function, can contribute to
      our protein engineering knowledge. 

PMID- 24688656
TI  - Cellulose degradation by oxidative enzymes.
AB  - Enzymatic degradation of plant biomass has attracted intensive research interest
      for the production of economically viable biofuels. Here we present an overview
      of the recent findings on biocatalysts implicated in the oxidative cleavage of
      cellulose, including polysaccharide monooxygenases (PMOs or LPMOs which stands
      for lytic PMOs), cellobiose dehydrogenases (CDHs) and members of carbohydrate
      binding module family 33 (CBM33). PMOs, a novel class of enzymes previously
      termed GH61s, boost the efficiency of common cellulases resulting in increased
      hydrolysis yields while lowering the protein loading needed. They act on the
      crystalline part of cellulose by generating oxidized and non-oxidized chain ends.
      An external electron donor is required for boosting the activity of PMOs. We
      discuss recent findings concerning their mechanism of action and identify issues
      and questions to be addressed in the future. 

PMID- 24688658
TI  - Technology prospecting on enzymes: application, marketing and engineering.
AB  - Enzymes are protein molecules functioning as specialized catalysts for chemical
      reactions. They have contributed greatly to the traditional and modern chemical
      industry by improving existing processes. In this article, we first give a survey
      of representative industrial applications of enzymes, focusing on the technical
      applications, feed industry, food processing and cosmetic products. The recent
      important developments and applications of enzymes in industry are reviewed. Then
      large efforts are dedicated to the worldwide enzyme market from the demand and
      production perspectives. Special attention is laid on the Chinese enzyme market.
      Although enzyme applications are being developed in full swing, breakthroughs are
      needed to overcome their weaknesses in maintaining activities during the
      catalytic processes. Strategies of metagomic analysis, cell surface display
      technology and cell-free system might give valuable solutions in novel enzyme
      exploiting and enzyme engineering. 

PMID- 24688657
TI  - Computational tools for rational protein engineering of aldolases.
AB  - In this mini-review we describe the different strategies for rational protein
      engineering and summarize the computational tools available. Computational tools
      can either be used to design focused libraries, to predict sequence-function
      relationships or for structure-based molecular modelling. This also includes de
      novo design of enzymes. Examples for protein engineering of aldolases and
      transaldolases are given in the second part of the mini-review. 

PMID- 24688660
TI  - A structural overview of GH61 proteins - fungal cellulose degrading
      polysaccharide monooxygenases.
AB  - Recent years have witnessed a spurt of activities in the elucidation of the
      molecular function of a class of proteins with great potential in biomass
      degradation. GH61 proteins are of fungal origin and were originally classified in
      family 61 of the glycoside hydrolases. From the beginning they were strongly
      suspected to be involved in cellulose degradation because of their expression
      profiles, despite very low detectable endoglucanase activities. A major
      breakthrough came from structure determination of the first members, establishing
      the presence of a divalent metal binding site and a similarity to bacterial
      proteins involved in chitin degradation. A second breakthrough came from the
      identification of cellulase boosting activity dependent on the integrity of the
      metal binding site. Finally very recently GH61 proteins were demonstrated to
      oxidatively cleave crystalline cellulose in a Cu and reductant dependant manner.
      This mini-review in particular focuses on the contribution that structure
      elucidation has made in the understanding of GH61 molecular function and reviews
      the currently known structures and the challenges remaining ahead for exploiting
      this new class of enzymes to the full. 

PMID- 24688659
TI  - From Molecular Phylogenetics to Quantum Chemistry: Discovering Enzyme Design
      Principles through Computation.

PMID- 24688661
TI  - Converting cells into cellular factories.

PMID- 24688662
TI  - The Biochemistry of Vitreoscilla hemoglobin.
AB  - The hemoglobin (VHb) from Vitreoscilla was the first bacterial hemoglobin
      discovered. Its structure and function have been extensively investigated, and
      engineering of a wide variety of heterologous organisms to express VHb has been
      performed to increase their growth and productivity. This strategy has shown
      promise in applications as far-ranging as the production of antibiotics and
      petrochemical replacements by microorganisms to increasing stress tolerance in
      plants. These applications of "VHb technology" have generally been of the "black
      box" variety, wherein the endpoint studied is an increase in the levels of a
      certain product or improved growth and survival. Their eventual optimization,
      however, will require a thorough understanding of the various functions and
      activities of VHb, and how VHb expression ripples to affect metabolism more
      generally. Here we review the current knowledge of these topics. VHb's functions
      all involve oxygen binding (and often delivery) in one way or another. Several
      biochemical and structure-function studies have provided an insight into the
      molecular details of this binding and delivery. VHb activities are varied. They
      include supply of oxygen to oxygenases and the respiratory chain, particularly
      under low oxygen conditions; oxygen sensing and modulation of transcription
      factor activity; and detoxification of NO, and seem to require interactions of
      VHb with "partner proteins". VHb expression affects the levels of ATP and NADH,
      although not enormously. VHb expression may affect the level of many compounds of
      intermediary metabolism, and, apparently, alters the levels of expression of many
      genes. Thus, the metabolic changes in organisms engineered to express VHb are
      likely to be numerous and complicated. 

PMID- 24688663
TI  - Metabolic engineering of lactic acid bacteria for the production of industrially
      important compounds.
AB  - Lactic acid bacteria (LAB) are receiving increased attention for use as cell
      factories for the production of metabolites with wide use by the food and
      pharmaceutical industries. The availability of efficient tools for genetic
      modification of LAB during the past decade permitted the application of metabolic
      engineering strategies at the levels of both the primary and the more complex
      secondary metabolism. The recent developments in the area with a focus on the
      production of industrially important metabolites will be discussed in this
      review. 

PMID- 24688664
TI  - Metabolic engineering of Corynebacterium glutamicum aimed at alternative carbon
      sources and new products.
AB  - Corynebacterium glutamicum is well known as the amino acid-producing workhorse of
      fermentation industry, being used for multi-million-ton scale production of
      glutamate and lysine for more than 60 years. However, it is only recently that
      extensive research has focused on engineering it beyond the scope of amino acids.
      Meanwhile, a variety of corynebacterial strains allows access to alternative
      carbon sources and/or allows production of a wide range of industrially relevant
      compounds. Some of these efforts set new standards in terms of titers and
      productivities achieved whereas others represent a proof-of-principle. These
      achievements manifest the position of C. glutamicum as an important industrial
      microorganism with capabilities far beyond the traditional amino acid production.
      In this review we focus on the state of the art of metabolic engineering of C.
      glutamicum for utilization of alternative carbon sources, (e.g. coming from
      wastes and unprocessed sources), and construction of C. glutamicum strains for
      production of new products such as diamines, organic acids and alcohols. 

PMID- 24688665
TI  - Optimization of enzyme parameters for fermentative production of biorenewable
      fuels and chemicals.
AB  - Microbial biocatalysts such as Escherichia coli and Saccharomyces cerevisiae have
      been extensively subjected to Metabolic Engineering for the fermentative
      production of biorenewable fuels and chemicals. This often entails the
      introduction of new enzymes, deletion of unwanted enzymes and efforts to fine
      tune enzyme abundance in order to attain the desired strain performance. Enzyme
      performance can be quantitatively described in terms of the Michaelis-Menten type
      parameters Km, turnover number kcat and Ki, which roughly describe the affinity
      of an enzyme for its substrate, the speed of a reaction and the enzyme
      sensitivity to inhibition by regulatory molecules. Here we describe examples of
      where knowledge of these parameters have been used to select, evolve or engineer
      enzymes for the desired performance and enabled increased production of
      biorenewable fuels and chemicals. Examples include production of ethanol,
      isobutanol, 1-butanol and tyrosine and furfural tolerance. The Michaelis-Menten
      parameters can also be used to judge the cofactor dependence of enzymes and
      quantify their preference for NADH or NADPH. Similarly, enzymes can be selected,
      evolved or engineered for the preferred cofactor preference. Examples of exporter
      engineering and selection are also discussed in the context of production of
      malate, valine and limonene. 

PMID- 24688666
TI  - Developing a yeast cell factory for the production of terpenoids.
AB  - Technological developments over the past century have made microbes the work
      horses of large scale industrial production processes. Current efforts focus on
      the metabolic engineering of microbial strains to produce high levels of
      desirable end-products. The arsenal of the contemporary metabolic engineer
      contains tools that allow either targeted rational interventions or global
      screens that combine classical approaches with -omics technologies. Production of
      terpenoids in S. cerevisiae presents a characteristic example of contemporary
      biotechnology that integrates all the variety of novel approaches used in
      metabolic engineering. Terpenoids have attracted significant interest as
      pharmaceuticals, flavour and fragrance additives, and, more recently, biofuels.
      The ongoing metabolic engineering efforts, combined with the continuously
      increasing number of terpene biosynthetic enzymes discovered will enable the
      economical and environmentally friendly production of a wide range of compounds. 

PMID- 24688667
TI  - Development of microorganisms for cellulose-biofuel consolidated bioprocessings:
      metabolic engineers' tricks.
AB  - Cellulose waste biomass is the most abundant and attractive substrate for
      "biorefinery strategies" that are aimed to produce high-value products (e.g.
      solvents, fuels, building blocks) by economically and environmentally sustainable
      fermentation processes. However, cellulose is highly recalcitrant to
      biodegradation and its conversion by biotechnological strategies currently
      requires economically inefficient multistep industrial processes. The need for
      dedicated cellulase production continues to be a major constraint to cost
      effective processing of cellulosic biomass. Research efforts have been aimed at
      developing recombinant microorganisms with suitable characteristics for single
      step biomass fermentation (consolidated bioprocessing, CBP). Two paradigms have
      been applied for such, so far unsuccessful, attempts: a) "native cellulolytic
      strategies", aimed at conferring high-value product properties to natural
      cellulolytic microorganisms; b) "recombinant cellulolytic strategies", aimed to
      confer cellulolytic ability to microorganisms exhibiting high product yields and
      titers. By starting from the description of natural enzyme systems for plant
      biomass degradation and natural metabolic pathways for some of the most valuable
      product (i.e. butanol, ethanol, and hydrogen) biosynthesis, this review describes
      state-of-the-art bottlenecks and solutions for the development of recombinant
      microbial strains for cellulosic biofuel CBP by metabolic engineering. Complexed
      cellulases (i.e. cellulosomes) benefit from stronger proximity effects and show
      enhanced synergy on insoluble substrates (i.e. crystalline cellulose) with
      respect to free enzymes. For this reason, special attention was held on
      strategies involving cellulosome/designer cellulosome-bearing recombinant
      microorganisms. 

PMID- 24688668
TI  - Genome-based Modeling and Design of Metabolic Interactions in Microbial
      Communities.
AB  - Biotechnology research is traditionally focused on individual microbial strains
      that are perceived to have the necessary metabolic functions, or the capability
      to have these functions introduced, to achieve a particular task. For many
      important applications, the development of such omnipotent microbes is an
      extremely challenging if not impossible task. By contrast, nature employs a
      radically different strategy based on synergistic combinations of different
      microbial species that collectively achieve the desired task. These natural
      communities have evolved to exploit the native metabolic capabilities of each
      species and are highly adaptive to changes in their environments. However,
      microbial communities have proven difficult to study due to a lack of suitable
      experimental and computational tools. With the advent of genome sequencing, omics
      technologies, bioinformatics and genome-scale modeling, researchers now have
      unprecedented capabilities to analyze and engineer the metabolism of microbial
      communities. The goal of this review is to summarize recent applications of
      genome-scale metabolic modeling to microbial communities. A brief introduction to
      lumped community models is used to motivate the need for genome-level
      descriptions of individual species and their metabolic interactions. The review
      of genome-scale models begins with static modeling approaches, which are
      appropriate for communities where the extracellular environment can be assumed to
      be time invariant or slowly varying. Dynamic extensions of the static modeling
      approach are described, and then applications of genome-scale models for design
      of synthetic microbial communities are reviewed. The review concludes with a
      summary of metagenomic tools for analyzing community metabolism and an outlook
      for future research. 

PMID- 24688669
TI  - Metabolic modelling in the development of cell factories by synthetic biology.
AB  - Cell factories are commonly microbial organisms utilized for bioconversion of
      renewable resources to bulk or high value chemicals. Introduction of novel
      production pathways in chassis strains is the core of the development of cell
      factories by synthetic biology. Synthetic biology aims to create novel biological
      functions and systems not found in nature by combining biology with engineering.
      The workflow of the development of novel cell factories with synthetic biology is
      ideally linear which will be attainable with the quantitative engineering
      approach, high-quality predictive models, and libraries of well-characterized
      parts. Different types of metabolic models, mathematical representations of
      metabolism and its components, enzymes and metabolites, are useful in particular
      phases of the synthetic biology workflow. In this minireview, the role of
      metabolic modelling in synthetic biology will be discussed with a review of
      current status of compatible methods and models for the in silico design and
      quantitative evaluation of a cell factory. 

PMID- 24688670
TI  - Dissecting complex polyketide biosynthesis.
AB  - Numerous bioactive natural products are synthesised by modular polyketide
      synthases. These compounds can be made in high yield by native multienzyme
      assembly lines. However, formation of analogues by genetically engineered systems
      is often considerably less efficient. Biochemical studies on intact polyketide
      synthase proteins have amassed a body of knowledge that is substantial but still
      incomplete. Recently, the constituent enzymes have been structurally
      characterised as discrete domains or didomains. These recombinant proteins have
      been used to reconstitute single extension cycles in vitro. This has given
      further insights into how the final stereochemistry of chiral centres in
      polyketides is determined. In addition, this approach has revealed how domains co
      operate to ensure efficient transfer of growing intermediates along the assembly
      line. This work is leading towards more effective re-programming of these enzymes
      for use in synthesis of new medicinal compounds. 

PMID- 24688671
TI  - Metabolic engineering of biocatalysts for carboxylic acids production.
AB  - Fermentation of renewable feedstocks by microbes to produce sustainable fuels and
      chemicals has the potential to replace petrochemical-based production. For
      example, carboxylic acids produced by microbial fermentation can be used to
      generate primary building blocks of industrial chemicals by either enzymatic or
      chemical catalysis. In order to achieve the titer, yield and productivity values
      required for economically viable processes, the carboxylic acid-producing
      microbes need to be robust and well-performing. Traditional strain development
      methods based on mutagenesis have proven useful in the selection of desirable
      microbial behavior, such as robustness and carboxylic acid production. On the
      other hand, rationally-based metabolic engineering, like genetic manipulation for
      pathway design, has becoming increasingly important to this field and has been
      used for the production of several organic acids, such as succinic acid, malic
      acid and lactic acid. This review investigates recent works on Saccharomyces
      cerevisiae and Escherichia coli, as well as the strategies to improve tolerance
      towards these chemicals. 

PMID- 24688672
TI  - Analyzing the genomic variation of microbial cell factories in the era of "New
      Biotechnology".
AB  - The application of genome-scale technologies, both experimental and in silico, to
      industrial biotechnology has allowed improving the conversion of biomass-derived
      feedstocks to chemicals, materials and fuels through microbial fermentation. In
      particular, due to rapidly decreasing costs and its suitability for identifying
      the genetic determinants of a phenotypic trait of interest, whole genome
      sequencing is expected to be one of the major driving forces in industrial
      biotechnology in the coming years. We present some of the recent studies that
      have successfully applied high-throughput sequencing technologies for finding the
      underlying molecular mechanisms for (a) improved carbon source utilization, (b)
      increased product formation, and (c) stress tolerance. We also discuss the
      strengths and weaknesses of different strategies for mapping industrially
      relevant genotype-to-phenotype links including exploiting natural diversity in
      natural isolates or crosses between isolates, classical mutagenesis and
      evolutionary engineering. 

PMID- 24688673
TI  - Engineered fluorescent proteins illuminate the bacterial periplasm.
AB  - The bacterial periplasm is of special interest whenever cell factories are
      designed and engineered. Recombinantely produced proteins are targeted to the
      periplasmic space of Gram negative bacteria to take advantage of the authentic N
      termini, disulfide bridge formation and easy accessibility for purification with
      less contaminating cellular proteins. The oxidizing environment of the periplasm
      promotes disulfide bridge formation - a prerequisite for proper folding of many
      proteins into their active conformation. In contrast, the most popular reporter
      protein in all of cell biology, Green Fluorescent Protein (GFP), remains inactive
      if translocated to the periplasmic space prior to folding. Here, the self
      catalyzed chromophore maturation is blocked by formation of covalent oligomers
      via interchain disulfide bonds in the oxidizing environment. However, different
      protein engineering approaches addressing folding and stability of GFP resulted
      in improved proteins with enhanced folding properties. Recent studies describe
      GFP variants that are not only active if translocated in their folded form via
      the twin-arginine translocation (Tat) pathway, but actively fold in the periplasm
      following general secretory pathway (Sec) and signal recognition particle (SRP)
      mediated secretion. This mini-review highlights the progress that enables new
      insights into bacterial export and periplasmic protein organization, as well as
      new biotechnological applications combining the advantages of the periplasmic
      production and the Aequorea-based fluorescent reporter proteins. 

PMID- 24688674
TI  - Beyond de-foaming: the effects of antifoams on bioprocess productivity.
AB  - Antifoams are often added to bioprocesses with little knowledge of their impact
      on the cells or product. However, it is known that certain antifoams can affect
      the growth rates of both prokaryotic and eukaryotic organisms in addition to
      changing surface properties such as lipid content, resulting in changes to
      permeability. This in turn can be beneficial to a recombinant protein production
      system for soluble proteins, as has been demonstrated by increased secretion of
      alpha-amylase and GFP, or achievement of greater yields of protein due to
      increased biomass. However, in some cases, certain concentrations of antifoams
      appear to have a detrimental effect upon cells and protein production, and the
      effects vary depending upon the protein being expressed. These findings emphasise
      the importance of optimising and understanding antifoam addition to bioprocesses.

PMID- 24688675
TI  - Systems biology and metabolic engineering of Arthrospira cell factories.
AB  - Arthrospira are attractive candidates to serve as cell factories for production
      of many valuable compounds useful for food, feed, fuel and pharmaceutical
      industries. In connection with the development of sustainable bioprocessing, it
      is a challenge to design and develop efficient Arthrospira cell factories which
      can certify effective conversion from the raw materials (i.e. CO2 and sun light)
      into desired products. With the current availability of the genome sequences and
      metabolic models of Arthrospira, the development of Arthrospira factories can now
      be accelerated by means of systems biology and the metabolic engineering
      approach. Here, we review recent research involving the use of Arthrospira cell
      factories for industrial applications, as well as the exploitation of systems
      biology and the metabolic engineering approach for studying Arthrospira. The
      current status of genomics and proteomics through the development of the genome
      scale metabolic model of Arthrospira, as well as the use of mathematical modeling
      to simulate the phenotypes resulting from the different metabolic engineering
      strategies are discussed. At the end, the perspective and future direction on
      Arthrospira cell factories for industrial biotechnology are presented. 

PMID- 24688676
TI  - Emerging engineering principles for yield improvement in microbial cell design.
AB  - Metabolic Engineering has undertaken a rapid transformation in the last ten years
      making real progress towards the production of a wide range of molecules and fine
      chemicals using a designed cellular host. However, the maximization of product
      yields through pathway optimization is a constant and central challenge of this
      field. Traditional methods used to improve the production of target compounds
      from engineered biosynthetic pathways in non-native hosts include: codon usage
      optimization, elimination of the accumulation of toxic intermediates or
      byproducts, enhanced production of rate-limiting enzymes, selection of
      appropriate promoter and ribosome binding sites, application of directed
      evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to
      be specific for each engineering project rather than a systematic practice based
      on a more generalizable strategy. In this mini-review, we highlight some novel
      and extensive approaches and tools intended to address the improvement of a
      target product formation, founded in sophisticated principles such as dynamic
      control, pathway genes modularization, and flux modeling. 

PMID- 24688677
TI  - Microbial Consortia Engineering for Cellular Factories: in vitro to in silico
      systems.
AB  - This mini-review discusses the current state of experimental and computational
      microbial consortia engineering with a focus on cellular factories. A discussion
      of promising ecological theories central to community resource usage is presented
      to facilitate interpretation of consortial designs. Recent case studies
      exemplifying different resource usage motifs and consortial assembly templates
      are presented. The review also highlights in silico approaches to design and to
      analyze consortia with an emphasis on stoichiometric modeling methods. The
      discipline of microbial consortia engineering possesses a widely accepted
      potential to generate highly novel and effective bio-catalysts for applications
      from biofuels to specialty chemicals to enhanced mineral recovery. 

PMID- 24688678
TI  - Importance of understanding the main metabolic regulation in response to the
      specific pathway mutation for metabolic engineering of Escherichia coli.
AB  - Recent metabolic engineering practice was briefly reviewed in particular for the
      useful metabolite production such as natural products and biofuel productions.
      With the emphasis on systems biology approach, the metabolic regulation of the
      main metabolic pathways in E. coli was discussed from the points of view of
      enzyme level (allosteric and phosphorylation/ dephosphorylation) regulation, and
      gene level (transcriptional) regulation. Then the effects of the specific pathway
      gene knockout such as pts, pgi, zwf, gnd, pyk, ppc, pckA, lpdA, pfl gene knockout
      on the metabolism in E. coli were overviewed from the systems biology point of
      view with possible application for strain improvement point. 

PMID- 24688679
TI  - Escherichia coli redox mutants as microbial cell factories for the synthesis of
      reduced biochemicals.
AB  - Bioprocesses conducted under conditions with restricted O2 supply are
      increasingly exploited for the synthesis of reduced biochemicals using different
      biocatalysts. The model facultative aerobe Escherichia coli, the microbial cell
      factory par excellence, has elaborate sensing and signal transduction mechanisms
      that respond to the availability of electron acceptors and alternative carbon
      sources in the surrounding environment. In particular, the ArcBA and CreBC two
      component signal transduction systems are largely responsible for the metabolic
      regulation of redox control in response to O2 availability and carbon source
      utilization, respectively. Significant advances in the understanding of the
      biochemical, genetic, and physiological duties of these regulatory systems have
      been achieved in recent years. This situation allowed to rationally-design novel
      engineering approaches that ensure optimal carbon and energy flows within central
      metabolism, as well as to manipulate redox homeostasis, in order to optimize the
      production of industrially-relevant metabolites. In particular, metabolic flux
      analysis provided new clues to understand the metabolic regulation mediated by
      the ArcBA and CreBC systems. Genetic manipulation of these regulators proved
      useful for designing microbial cells factories tailored for the synthesis of
      reduced biochemicals with added value, such as poly(3-hydroxybutyrate), under
      conditions with restricted O2 supply. This network-wide strategy is in contrast
      with traditional metabolic engineering approaches, that entail direct
      modification of the pathway(s) at stake, and opens new avenues for the targeted
      modulation of central catabolic pathways at the transcriptional level. 

PMID- 24688680
TI  - Engineering microbes for plant polyketide biosynthesis.
AB  - Polyketides are an important group of secondary metabolites, many of which have
      important industrial applications in the food and pharmaceutical industries.
      Polyketides are synthesized from one of three classes of enzymes differentiated
      by their biochemical features and product structure: type I, type II or type III
      polyketide synthases (PKSs). Plant type III PKS enzymes, which will be the main
      focus of this review, are relatively small homodimeric proteins that catalyze
      iterative decarboxylative condensations of malonyl units with a CoA-linked
      starter molecule. This review will describe the plant type III polyketide
      synthetic pathway, including the synthesis of chalcones, stilbenes and
      curcuminoids, as well as recent work on the synthesis of these polyketides in
      heterologous organisms. The limitations and bottlenecks of heterologous
      expression as well as attempts at creating diversity through the synthesis of
      novel "unnatural" polyketides using type III PKSs will also be discussed.
      Although synthetic production of plant polyketides is still in its infancy, their
      potential as useful bioactive compounds makes them an extremely interesting area
      of study. 

PMID- 24688681
TI  - Combinatorial approaches for inverse metabolic engineering applications.
AB  - Traditional metabolic engineering analyzes biosynthetic and physiological
      pathways, identifies bottlenecks, and makes targeted genetic modifications with
      the ultimate goal of increasing the production of high-value products in living
      cells. Such efforts have led to the development of a variety of organisms with
      industrially relevant properties. However, there are a number of cellular
      phenotypes important for research and the industry for which the rational
      selection of cellular targets for modification is not easy or possible. In these
      cases, strain engineering can be alternatively carried out using "inverse
      metabolic engineering", an approach that first generates genetic diversity by
      subjecting a population of cells to a particular mutagenic process, and then
      utilizes genetic screens or selections to identify the clones exhibiting the
      desired phenotype. Given the availability of an appropriate screen for a
      particular property, the success of inverse metabolic engineering efforts usually
      depends on the level and quality of genetic diversity which can be generated.
      Here, we review classic and recently developed combinatorial approaches for
      creating such genetic diversity and discuss the use of these methodologies in
      inverse metabolic engineering applications. 

PMID- 24688683
TI  - Analytical techniques & applications of metabolomics in systems medicine and
      systems biotechnology.

PMID- 24688682
TI  - Bioprocess systems engineering: transferring traditional process engineering
      principles to industrial biotechnology.
AB  - The complexity of the regulatory network and the interactions that occur in the
      intracellular environment of microorganisms highlight the importance in
      developing tractable mechanistic models of cellular functions and systematic
      approaches for modelling biological systems. To this end, the existing process
      systems engineering approaches can serve as a vehicle for understanding,
      integrating and designing biological systems and processes. Here, we review the
      application of a holistic approach for the development of mathematical models of
      biological systems, from the initial conception of the model to its final
      application in model-based control and optimisation. We also discuss the use of
      mechanistic models that account for gene regulation, in an attempt to advance the
      empirical expressions traditionally used to describe micro-organism growth
      kinetics, and we highlight current and future challenges in mathematical biology.
      The modelling research framework discussed herein could prove beneficial for the
      design of optimal bioprocesses, employing rational and feasible approaches
      towards the efficient production of chemicals and pharmaceuticals. 

PMID- 24688684
TI  - LC-MS metabolomics from study design to data-analysis - using a versatile
      pathogen as a test case.
AB  - Thanks to significant improvements in LC-MS technology, metabolomics is
      increasingly used as a tool to discriminate the responses of organisms to various
      stimuli or drugs. In this minireview we discuss all aspects of the LC-MS
      metabolomics pipeline, using a complex and versatile model organism, Leishmania
      donovani, as an illustrative example. The benefits of a hyphenated mass
      spectrometry platform and a detailed overview of the entire experimental pipeline
      from sampling, sample storage and sample list set-up to LC-MS measurements and
      the generation of meaningful results with state-of-the-art data-analysis software
      will be thoroughly discussed. Finally, we also highlight important pitfalls in
      the processing of LC-MS data and comment on the benefits of implementing
      metabolomics in a systems biology approach. 

PMID- 24688685
TI  - Computational tools for the secondary analysis of metabolomics experiments.
AB  - Metabolomics experiments have become commonplace in a wide variety of
      disciplines. By identifying and quantifying metabolites researchers can achieve a
      systems level understanding of metabolism. These studies produce vast swaths of
      data which are often only lightly interpreted due to the overwhelmingly large
      amount of variables that are measured. Recently, a number of computational tools
      have been developed which enable much deeper analysis of metabolomics data. These
      data have been difficult to interpret as understanding the connections between
      dozens of altered metabolites has often relied on the biochemical knowledge of
      researchers and their speculations. Modern biochemical databases provide
      information about the interconnectivity of metabolism which can be automatically
      polled using metabolomics secondary analysis tools. Starting with lists of
      altered metabolites, there are two main types of analysis: enrichment analysis
      computes which metabolic pathways have been significantly altered whereas
      metabolite mapping contextualizes the abundances and significances of measured
      metabolites into network visualizations. Many different tools have been developed
      for one or both of these applications. In this review the functionality and use
      of these software is discussed. Together these novel secondary analysis tools
      will enable metabolomics researchers to plumb the depths of their data and
      produce farther reaching biological conclusions than ever before. 

PMID- 24688687
TI  - A rough guide to metabolite identification using high resolution liquid
      chromatography mass spectrometry in metabolomic profiling in metazoans.
AB  - Compound identification in mass spectrometry based metabolomics can be a problem
      but sometimes the problem seems to be presented in an over complicated way. The
      current review focuses on metazoans where the range of metabolites is more
      restricted than for example in plants. The focus is on liquid chromatography with
      high resolution mass spectrometry where it is proposed that most of the problems
      in compound identification relate to structural isomers rather than to isobaric
      compounds. Thus many of the problems faced relate to separation of isomers, which
      is usually required even if fragmentation is used to support structural
      identification. Many papers report the use of MS/MS or MS(2) as an adjunct to the
      identification of known metabolites but there a few examples in metabolomics
      studies of metazoans of complete structure elucidation of novel metabolites or
      metabolites where no authentic standards are available for comparison. 

PMID- 24688686
TI  - Metabolomics in the identification of biomarkers of dietary intake.
AB  - Traditional methods for assessing dietary exposure can be unreliable, with under
      reporting one of the main problems. In an attempt to overcome such problems there
      is increasing interest in identifying biomarkers of dietary intake to provide a
      more accurate measurement. Metabolomics is an analytical technique that aims to
      identify and quantify small metabolites. Recently, there has been an increased
      interest in the application of metabolomics coupled with statistical analysis for
      the identification of dietary biomarkers, with a number of putative biomarkers
      identified. This minireview focuses on metabolomics based approaches and
      highlights some of the key successes. 

PMID- 24688688
TI  - Untargeted metabolomics: an emerging approach to determine the composition of
      herbal products.
AB  - Natural remedies, such as those based on traditional Chinese medicines, have
      become more popular also in western countries over the last 10 years. The
      composition of these herbal products is largely unknown and difficult to
      determine. Moreover, since plants respond to their environment changing the
      metabolome, the composition of plant material can vary depending on the plant
      growth conditions. However, there is a growing need of a deeper knowledge on such
      natural remedies also in view of the growing number of reports of toxicity
      following the consumption of herbal supplements. Untargeted metabolomics is a
      useful approach for the simultaneous analysis of many compounds in herbal
      products. In particular, liquid chromatography/mass spectrometry (LC-MS) can
      determine presence, amount and sometime structures of plant metabolites in
      complex herbal mixtures, with significant advantages over techniques such as
      nuclear magnetic resonance (NMR) spectroscopy and gas chromatography/mass
      spectrometry (GC-MS). 

PMID- 24688689
TI  - LC-MS-based Metabolomics of Xenobiotic-induced Toxicities.
AB  - Xenobiotic exposure, especially high-dose or repeated exposure of xenobiotics,
      can elicit detrimental effects on biological systems through diverse mechanisms.
      Changes in metabolic systems, including formation of reactive metabolites and
      disruption of endogenous metabolism, are not only the common consequences of
      toxic xenobiotic exposure, but in many cases are the major causes behind
      development of xenobiotic-induced toxicities (XIT). Therefore, examining the
      metabolic events associated with XIT generates mechanistic insights into the
      initiation and progression of XIT, and provides guidance for prevention and
      treatment. Traditional bioanalytical platforms that target only a few suspected
      metabolites are capable of validating the expected outcomes of xenobiotic
      exposure. However, these approaches lack the capacity to define global changes
      and to identify unexpected events in the metabolic system. Recent developments in
      high-throughput metabolomics have dramatically expanded the scope and potential
      of metabolite analysis. Among all analytical techniques adopted for metabolomics,
      liquid chromatography-mass spectrometry (LC-MS) has been most widely used for
      metabolomic investigations of XIT due to its versatility and sensitivity in
      metabolite analysis. In this review, technical platform of LC-MS-based
      metabolomics, including experimental model, sample preparation, instrumentation,
      and data analysis, are discussed. Applications of LC-MS-based metabolomics in
      exploratory and hypothesis-driven investigations of XIT are illustrated by case
      studies of xenobiotic metabolism and endogenous metabolism associated with
      xenobiotic exposure. 

PMID- 24688690
TI  - Statistical methods for the analysis of high-throughput metabolomics data.
AB  - Metabolomics is a relatively new high-throughput technology that aims at
      measuring all endogenous metabolites within a biological sample in an unbiased
      fashion. The resulting metabolic profiles may be regarded as functional
      signatures of the physiological state, and have been shown to comprise effects of
      genetic regulation as well as environmental factors. This potential to connect
      genotypic to phenotypic information promises new insights and biomarkers for
      different research fields, including biomedical and pharmaceutical research. In
      the statistical analysis of metabolomics data, many techniques from other omics
      fields can be reused. However recently, a number of tools specific for
      metabolomics data have been developed as well. The focus of this mini review will
      be on recent advancements in the analysis of metabolomics data especially by
      utilizing Gaussian graphical models and independent component analysis. 

PMID- 24688691
TI  - Data Mining Methods for Omics and Knowledge of Crude Medicinal Plants toward Big
      Data Biology.
AB  - Molecular biological data has rapidly increased with the recent progress of the
      Omics fields, e.g., genomics, transcriptomics, proteomics and metabolomics that
      necessitates the development of databases and methods for efficient storage,
      retrieval, integration and analysis of massive data. The present study reviews
      the usage of KNApSAcK Family DB in metabolomics and related area, discusses
      several statistical methods for handling multivariate data and shows their
      application on Indonesian blended herbal medicines (Jamu) as a case study.
      Exploration using Biplot reveals many plants are rarely utilized while some
      plants are highly utilized toward specific efficacy. Furthermore, the ingredients
      of Jamu formulas are modeled using Partial Least Squares Discriminant Analysis
      (PLS-DA) in order to predict their efficacy. The plants used in each Jamu
      medicine served as the predictors, whereas the efficacy of each Jamu provided the
      responses. This model produces 71.6% correct classification in predicting
      efficacy. Permutation test then is used to determine plants that serve as main
      ingredients in Jamu formula by evaluating the significance of the PLS-DA
      coefficients. Next, in order to explain the role of plants that serve as main
      ingredients in Jamu medicines, information of pharmacological activity of the
      plants is added to the predictor block. Then N-PLS-DA model, multiway version of
      PLS-DA, is utilized to handle the three-dimensional array of the predictor block.
      The resulting N-PLS-DA model reveals that the effects of some pharmacological
      activities are specific for certain efficacy and the other activities are diverse
      toward many efficacies. Mathematical modeling introduced in the present study can
      be utilized in global analysis of big data targeting to reveal the underlying
      biology. 

PMID- 24688692
TI  - Integrated LC-MS/MS system for plant metabolomics.
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is highly sensitive,
      selective, and enables extensive detection of metabolites within a sample. The
      result allows us to characterize comprehensive metabolite accumulation patterns
      without dependence on authentic standard compounds and isolation of the
      individual metabolites. A reference database search is essential for the
      structural assignment process of un-targeted MS and MS/MS data. Moreover, the
      characterization of unknown metabolites is challenging, since these cannot be
      assigned a candidate structure by using a reference database. In this case study,
      integrated LC-MS/MS based plant metabolomics allows us to detect several hundred
      metabolites in a sample; and integrated omics analyses, e.g., large-scale reverse
      genetics, linkage mapping, and association mapping, provides a powerful tool for
      candidate structure selection or rejection. We also examine emerging technology
      and applications for LC-MS/MS-based un-targeted plant metabolomics. These
      activities promote the characterization of massive extended detectable
      metabolites. 

PMID- 24688693
TI  - Targeted, LCMS-based Metabolomics for Quantitative Measurement of NAD(+)
      Metabolites.
AB  - Nicotinamide adenine dinucleotide (NAD(+)) is a coenzyme for hydride transfer
      reactions and a substrate for sirtuins and other NAD(+)-consuming enzymes. The
      abundance of NAD (+), NAD(+) biosynthetic intermediates, and related nucleotides
      reflects the metabolic state of cells and tissues. High performance liquid
      chromatography (HPLC) followed by ultraviolet-visible (UV-Vis) spectroscopic
      analysis of NAD(+) metabolites does not offer the specificity and sensitivity
      necessary for robust quantification of complex samples. Thus, we developed a
      targeted, quantitative assay of the NAD(+) metabolome with the use of HPLC
      coupled to mass spectrometry. Here we discuss NAD(+) metabolism as well as the
      technical challenges required for reliable quantification of the NAD(+)
      metabolites. The new method incorporates new separations and improves upon a
      previously published method that suffered from the problem of ionization
      suppression for particular compounds. 

PMID- 24688694
TI  - Spectral deconvolution for gas chromatography mass spectrometry-based
      metabolomics: current status and future perspectives.
AB  - Mass spectrometry coupled to gas chromatography (GC-MS) has been widely applied
      in the field of metabolomics. Success of this application has benefited greatly
      from computational workflows that process the complex raw mass spectrometry data
      and extract the qualitative and quantitative information of metabolites. Among
      the computational algorithms within a workflow, deconvolution is critical since
      it reconstructs a pure mass spectrum for each component that the mass
      spectrometer observes. Based on the pure spectrum, the corresponding component
      can be eventually identified and quantified. Deconvolution is challenging due to
      the existence of co-elution. In this review, we focus on progress that has been
      made in the development of deconvolution algorithms and provide thoughts on
      future developments that will expand the application of GC-MS in metabolomics. 

PMID- 24688695
TI  - Fusing similarity rankings in ligand-based virtual screening.
AB  - Data fusion is the name given to a range of methods for combining multiple
      sources of evidence. This mini-review summarizes the use of one such class of
      methods for combining the rankings obtained when similarity searching is used for
      ligand-based virtual screening. Two main approaches are described: similarity
      fusion involves combining rankings from single searches based on multiple
      similarity measures; and group fusion involves combining rankings from multiple
      searches based on a single similarity measure. The review then focuses on the
      rules that are available for combining similarity rankings, and on the evidence
      that exists for the superiority of fusion-based methods over conventional
      similarity searching. 

PMID- 24688696
TI  - Conformational sampling in template-free protein loop structure modeling: an
      overview.
AB  - Accurately modeling protein loops is an important step to predict three
      dimensional structures as well as to understand functions of many proteins.
      Because of their high flexibility, modeling the three-dimensional structures of
      loops is difficult and is usually treated as a "mini protein folding problem"
      under geometric constraints. In the past decade, there has been remarkable
      progress in template-free loop structure modeling due to advances of
      computational methods as well as stably increasing number of known structures
      available in PDB. This mini review provides an overview on the recent
      computational approaches for loop structure modeling. In particular, we focus on
      the approaches of sampling loop conformation space, which is a critical step to
      obtain high resolution models in template-free methods. We review the potential
      energy functions for loop modeling, loop buildup mechanisms to satisfy geometric
      constraints, and loop conformation sampling algorithms. The recent loop modeling
      results are also summarized. 

PMID- 24688697
TI  - Comparison and enumeration of chemical graphs.
AB  - Chemical compounds are usually represented as graph structured data in computers.
      In this review article, we overview several graph classes relevant to chemical
      compounds and the computational complexities of several fundamental problems for
      these graph classes. In particular, we consider the following problems:
      determining whether two chemical graphs are identical, determining whether one
      input chemical graph is a part of the other input chemical graph, finding a
      maximum common part of two input graphs, finding a reaction atom mapping,
      enumerating possible chemical graphs, and enumerating stereoisomers. We also
      discuss the relationship between the fifth problem and kernel functions for
      chemical compounds. 

PMID- 24688698
TI  - Chemical structure identification in metabolomics: computational modeling of
      experimental features.
AB  - The identification of compounds in complex mixtures remains challenging despite
      recent advances in analytical techniques. At present, no single method can detect
      and quantify the vast array of compounds that might be of potential interest in
      metabolomics studies. High performance liquid chromatography/mass spectrometry
      (HPLC/MS) is often considered the analytical method of choice for analysis of
      biofluids. The positive identification of an unknown involves matching at least
      two orthogonal HPLC/MS measurements (exact mass, retention index, drift time
      etc.) against an authentic standard. However, due to the limited availability of
      authentic standards, an alternative approach involves matching known and measured
      features of the unknown compound with computationally predicted features for a
      set of candidate compounds downloaded from a chemical database. Computationally
      predicted features include retention index, ECOM50 (energy required to decompose
      50% of a selected precursor ion in a collision induced dissociation cell), drift
      time, whether the unknown compound is biological or synthetic and a collision
      induced dissociation (CID) spectrum. Computational predictions are used to filter
      the initial "bin" of candidate compounds. The final output is a ranked list of
      candidates that best match the known and measured features. In this mini review,
      we discuss cheminformatics methods underlying this database search-filter
      identification approach. 

PMID- 24688700
TI  - Multivariate linear QSPR/QSAR models: Rigorous evaluation of variable selection
      for PLS.
AB  - Basic chemometric methods for making empirical regression models for QSPR/QSAR
      are briefly described from a user's point of view. Emphasis is given to PLS
      regression, simple variable selection and a careful and cautious evaluation of
      the performance of PLS models by repeated double cross validation (rdCV). A
      demonstration example is worked out for QSPR models that predict gas
      chromatographic retention indices (values between 197 and 504 units) of 209
      polycyclic aromatic compounds (PAC) from molecular descriptors generated by
      Dragon software. Most favorable models were obtained from data sets containing
      also descriptors from 3D structures with all H-atoms (computed by Corina
      software), using stepwise variable selection (reducing 2688 descriptors to a
      subset of 22). The final QSPR model has typical prediction errors for the
      retention index of +/-12 units (95% tolerance interval, for test set objects).
      Programs and data are provided as supplementary material for the open source R
      software environment. 

PMID- 24688699
TI  - Small world network strategies for studying protein structures and binding.
AB  - Small world network concepts provide many new opportunities to investigate the
      complex three dimensional structures of protein molecules. This mini-review
      explores the published literature on using small-world network approaches to
      study protein structure, with emphasis on the different combinations of
      descriptors that have been tested, on studies involving ligand binding in protein
      ligand complexes, and on protein-protein complexes. The benefits and success of
      small world network approaches, which change the focus from specific interactions
      to the local environment, even to non-local phenomenon, are described. The
      purpose is to show the different ways that small world network concepts have been
      used for building new computational models for studying protein structure and
      function, and for extending and improving existing modelling approaches. 

PMID- 24688702
TI  - Methods for Similarity-based Virtual Screening.
AB  - Developing new medical drugs is expensive. Among the first steps is a screening
      process, in which molecules in existing chemical libraries are tested for
      activity against a given target. This requires a lot of resources and manpower.
      Therefore it has become common to perform a virtual screening, where computers
      are used for predicting the activity of very large libraries of molecules, to
      identify the most promising leads for further laboratory experiments. Since
      computer simulations generally require fewer resources than physical
      experimentation this can lower the cost of medical and biological research
      significantly. In this paper we review practically fast algorithms for screening
      databases of molecules in order to find molecules that are sufficiently similar
      to a query molecule. 

PMID- 24688701
TI  - Molecular Dynamics Computer Simulations of Multidrug RND Efflux Pumps.
AB  - Over-expression of multidrug efflux pumps of the Resistance Nodulation Division
      (RND) protein super family counts among the main causes for microbial resistance
      against pharmaceuticals. Understanding the molecular basis of this process is one
      of the major challenges of modern biomedical research, involving a broad range of
      experimental and computational techniques. Here we review the current state of
      RND transporter investigation employing molecular dynamics simulations providing
      conformational samples of transporter components to obtain insights into the
      functional mechanism underlying efflux pump-mediated antibiotics resistance in
      Escherichia coli and Pseudomonas aeruginosa. 

PMID- 24688703
TI  - A frequency-based linguistic approach to protein decoding and design: Simple
      concepts, diverse applications, and the SCS Package.
AB  - Protein structure and function information is coded in amino acid sequences.
      However, the relationship between primary sequences and three-dimensional
      structures and functions remains enigmatic. Our approach to this fundamental
      biochemistry problem is based on the frequencies of short constituent sequences
      (SCSs) or words. A protein amino acid sequence is considered analogous to an
      English sentence, where SCSs are equivalent to words. Availability scores, which
      are defined as real SCS frequencies in the non-redundant amino acid database
      relative to their probabilistically expected frequencies, demonstrate the
      biological usage bias of SCSs. As a result, this frequency-based linguistic
      approach is expected to have diverse applications, such as secondary structure
      specifications by structure-specific SCSs and immunological adjuvants with rare
      or non-existent SCSs. Linguistic similarities (e.g., wide ranges of scale-free
      distributions) and dissimilarities (e.g., behaviors of low-rank samples) between
      proteins and the natural English language have been revealed in the rank
      frequency relationships of SCSs or words. We have developed a web server, the SCS
      Package, which contains five applications for analyzing protein sequences based
      on the linguistic concept. These tools have the potential to assist researchers
      in deciphering structurally and functionally important protein sites, species
      specific sequences, and functional relationships between SCSs. The SCS Package
      also provides researchers with a tool to construct amino acid sequences de novo
      based on the idiomatic usage of SCSs. 

PMID- 24688705
TI  - Reviewing and identifying amino acids of human, murine, canine and equine TLR4 /
      MD-2 receptor complexes conferring endotoxic innate immunity activation by
      LPS/lipid A, or antagonistic effects by Eritoran, in contrast to species
      dependent modulation by lipid IVa.
AB  - There is literature evidence gathered throughout the last two decades reflecting
      unexpected species differences concerning the immune response to lipid IVa which
      provides the opportunity to gain more detailed insight by the molecular modeling
      approach described in this study. Lipid IVa is a tetra-acylated precursor of
      lipid A in the biosynthesis of lipopolysaccharide (LPS) in Gram-negative
      bacteria. Lipid A of the prototypic E. coli-type is a hexa-acylated structure
      that acts as an agonist in all tested mammalian species by innate
      immunorecognition via the Toll-like receptor 4 (TLR4)/myeloid differentiation
      factor 2 (MD-2) receptor complex. In contrast, lipid IVa is proinflammatory in
      mouse cells (agonism) but it remains inactive to human macrophages and even
      antagonizes the action of potent agonists like E. coli-type lipid A. This
      particular ambivalent activity profile of lipid IVa has been confirmed in other
      mammalian species: in equine cells Lipid IVa also acts in a weak agonistic
      manner, whereas being inactive and antagonizing the lipid A-induced activation of
      canine TLR4/MD-2. Intriguingly, the respective TLR4 amino acid sequences of the
      latter species are more identical to the human (67%, 68%) than to the murine
      (62%, 58%) ortholog. In order to address the unpaired activity-sequence dualism
      for human, murine, canine and equine species regarding the activity of lipid IVa
      as compared to LPS and lipid A and, we review the literature and computationally
      pinpoint the differential biological effects of lipid IVa versus LPS and lipid A
      to specific amino acid residues. In contrast to lipid IVa the structurally
      related synthetic compound Eritoran (E5564) acts consistently in an antagonistic
      manner in these mammalian species and serves as a reference ligand for molecular
      modeling in this study. The combined evaluation of data sets provided by prior
      studies and in silico homology mapping of differential residues of TLR4/MD-2
      complexes lends detailed insight into the driving forces of the characteristic
      binding modes of the lipid A domain in LPS and the precursor structure lipid IVa
      to the receptor complex in individual mammalian species. 

PMID- 24688706
TI  - Automated detection of structural alerts (chemical fragments) in (eco)toxicology.
AB  - This mini-review describes the evolution of different algorithms dedicated to the
      automated discovery of chemical fragments associated to (eco)toxicological
      endpoints. These structural alerts correspond to one of the most interesting
      approach of in silico toxicology due to their direct link with specific
      toxicological mechanisms. A number of expert systems are already available but,
      since the first work in this field which considered a binomial distribution of
      chemical fragments between two datasets, new data miners were developed and
      applied with success in chemoinformatics. The frequency of a chemical fragment in
      a dataset is often at the core of the process for the definition of its
      toxicological relevance. However, recent progresses in data mining provide new
      insights into the automated discovery of new rules. Particularly, this review
      highlights the notion of Emerging Patterns that can capture contrasts between
      classes of data. 

PMID- 24688704
TI  - Current progress in Structure-Based Rational Drug Design marks a new mindset in
      drug discovery.
AB  - The past decade has witnessed a paradigm shift in preclinical drug discovery with
      structure-based drug design (SBDD) making a comeback while high-throughput
      screening (HTS) methods have continued to generate disappointing results. There
      is a deficit of information between identified hits and the many criteria that
      must be fulfilled in parallel to convert them into preclinical candidates that
      have a real chance to become a drug. This gap can be bridged by investigating the
      interactions between the ligands and their receptors. Accurate calculations of
      the free energy of binding are still elusive; however progresses were made with
      respect to how one may deal with the versatile role of water. A corpus of
      knowledge combining X-ray structures, bioinformatics and molecular modeling
      techniques now allows drug designers to routinely produce receptor homology
      models of increasing quality. These models serve as a basis to establish and
      validate efficient rationales used to tailor and/or screen virtual libraries with
      enhanced chances of obtaining hits. Many case reports of successful SBDD show how
      synergy can be gained from the combined use of several techniques. The role of
      SBDD with respect to two different classes of widely investigated pharmaceutical
      targets: (a) protein kinases (PK) and (b) G-protein coupled receptors (GPCR) is
      discussed. Throughout these examples prototypical situations covering the current
      possibilities and limitations of SBDD are presented. 

PMID- 24688707
TI  - Membrane Packing Problems: A short Review on computational Membrane Modeling
      Methods and Tools.
AB  - The use of model membranes is currently part of the daily workflow for many
      biochemical and biophysical disciplines. These membranes are used to analyze the
      behavior of small substances, to simulate transport processes, to study the
      structure of macromolecules or for illustrative purposes. But, how can these
      membrane structures be generated? This mini review discusses a number of ways to
      obtain these structures. First, the problem will be formulated as the Membrane
      Packing Problem. It will be shown that the theoretical problem of placing
      proteins and lipids onto a membrane area differ significantly. Thus, two sub
      problems will be defined and discussed. Then, different - partly historical -
      membrane modeling methods will be introduced. And finally, membrane modeling
      tools will be evaluated which are able to semi-automatically generate these model
      membranes and thus, drastically accelerate and simplify the membrane generation
      process. The mini review concludes with advice about which tool is appropriate
      for which application case. 

PMID- 24688708
TI  - MD simulation studies to investigate iso-energetic conformational behaviour of
      modified nucleosides m(2)G and m(2) 2G present in tRNA.
AB  - Modified nucleic acid bases are most commonly found in tRNA. These may contain
      modifications from simple methylation to addition of bulky groups. Methylation of
      the four canonical nucleotide bases at a wide variety of positions is
      particularly prominent among the known modification. Methylation of N2 group of
      guanine is a relatively common modification in tRNA and rRNA. N2-methylguanosine
      (m(2)G) is the second most often encountered nucleoside in E. coli tRNAs. N2, N2-
      dimethylguanosine (m(2) 2G) is found in the majority of eukaryotic tRNAs and
      involved in forming base pair interactions with adjacent bases. Hence, in order
      to understand the structural significance of these methylated nucleic acid bases
      we have carried out molecular dynamics simulation to see the salvation effect.
      The results obtained shows iso-energetic conformational behaviors for m(2)G and
      m(2) 2G. The simulation trajectory of m(2)G shows regular periodical fluctuations
      suggesting that m(2)G is equally stable as either s-cis or s-trans rotamers. The
      two rotamers of m(2)G may interact canonically or non-canonically with opposite
      base as s-trans m(2)G26:C/A/U44 and s-cis m(2)G26:A/U44. The free rotations
      around the C-N bond could be the possible reason for these iso-energetic
      conformations. Dimethylation of G has almost no influence on base pairing with
      either A or U. Thus, these results reveal that modified nucleosides m(2)G and
      m(2) 2G may play an important role to prevent tRNA from adopting the unusual
      mitochondrial like conformation. 

PMID- 24688709
TI  - ChromatoGate: A Tool for Detecting Base Mis-Calls in Multiple Sequence Alignments
      by Semi-Automatic Chromatogram Inspection.
AB  - Automated DNA sequencers generate chromatograms that contain raw sequencing data.
      They also generate data that translates the chromatograms into molecular
      sequences of A, C, G, T, or N (undetermined) characters. Since chromatogram
      translation programs frequently introduce errors, a manual inspection of the
      generated sequence data is required. As sequence numbers and lengths increase,
      visual inspection and manual correction of chromatograms and corresponding
      sequences on a per-peak and per-nucleotide basis becomes an error-prone, time
      consuming, and tedious process. Here, we introduce ChromatoGate (CG), an open
      source software that accelerates and partially automates the inspection of
      chromatograms and the detection of sequencing errors for bidirectional sequencing
      runs. To provide users full control over the error correction process, a fully
      automated error correction algorithm has not been implemented. Initially, the
      program scans a given multiple sequence alignment (MSA) for potential sequencing
      errors, assuming that each polymorphic site in the alignment may be attributed to
      a sequencing error with a certain probability. The guided MSA assembly procedure
      in ChromatoGate detects chromatogram peaks of all characters in an alignment that
      lead to polymorphic sites, given a user-defined threshold. The threshold value
      represents the sensitivity of the sequencing error detection mechanism. After
      this pre-filtering, the user only needs to inspect a small number of peaks in
      every chromatogram to correct sequencing errors. Finally, we show that correcting
      sequencing errors is important, because population genetic and phylogenetic
      inferences can be misled by MSAs with uncorrected mis-calls. Our experiments
      indicate that estimates of population mutation rates can be affected two- to
      three-fold by uncorrected errors. 

PMID- 24688710
TI  - Tribology of bio-inspired nanowrinkled films on ultrasoft substrates.
AB  - Biomimetic design of new materials uses nature as antetype, learning from
      billions of years of evolution. This work emphasizes the mechanical and
      tribological properties of skin, combining both hardness and wear resistance of
      its surface (the stratum corneum) with high elasticity of the bulk (epidermis,
      dermis, hypodermis). The key for combination of such opposite properties is
      wrinkling, being consequence of intrinsic stresses in the bulk (soft tissue):
      Tribological contact to counterparts below the stress threshold for tissue trauma
      occurs on the thick hard stratum corneum layer pads, while tensile loads smooth
      out wrinkles in between these pads. Similar mechanism offers high tribological
      resistance to hard films on soft, flexible polymers, which is shown for diamond
      like carbon (DLC) and titanium nitride thin films on ultrasoft polyurethane and
      harder polycarbonate substrates. The choice of these two compared substrate
      materials will show that ultra-soft substrate materials are decisive for the
      distinct tribological material. Hierarchical wrinkled structures of films on
      these substrates are due to high intrinsic compressive stress, which evolves
      during high energetic film growth. Incremental relaxation of these stresses
      occurs by compound deformation of film and elastic substrate surface, appearing
      in hierarchical nano-wrinkles. Nano-wrinkled topographies enable high elastic
      deformability of thin hard films, while overstressing results in zigzag film
      fracture along larger hierarchical wrinkle structures. Tribologically, these
      fracture mechanisms are highly important for ploughing and sliding of sharp and
      flat counterparts on hard-coated ultra-soft substrates like polyurethane.
      Concentration of polyurethane deformation under the applied normal loads occurs
      below these zigzag cracks. Unloading closes these cracks again. Even cyclic
      testing do not lead to film delamination and retain low friction behavior, if the
      adhesion to the substrate is high and the initial friction coefficient of the
      film against the sliding counterpart low, e.g. found for DLC. 

PMID- 24688711
TI  - Biomarker identification in breast cancer: Beta-adrenergic receptor signaling and
      pathways to therapeutic response.
AB  - Recent preclinical studies have associated beta-adrenergic receptor (beta-AR)
      signaling with breast cancer pathways such as progression and metastasis. These
      findings have been supported by clinical and epidemiological studies which
      examined the effect of beta-blocker therapy on breast cancer metastasis,
      recurrence and mortality. Results from these studies have provided initial
      evidence for the inhibition of cell migration in breast cancer by beta-blockers
      and have introduced the beta-adrenergic receptor pathways as a target for
      therapy. This paper analyzes gene expression profiles in breast cancer patients,
      utilising Artificial Neural Networks (ANNs) to identify molecular signatures
      corresponding to possible disease management pathways and biomarker treatment
      strategies associated with beta-2-adrenergic receptor (ADRB2) cell signaling. The
      adrenergic receptor relationship to cancer is investigated in order to validate
      the results of recent studies that suggest the use of beta-blockers for breast
      cancer therapy. A panel of genes is identified which has previously been reported
      to play an important role in cancer and also to be involved in the beta
      adrenergic receptor signaling. 

PMID- 24688712
TI  - Biomarker signature identification in "omics" data with multi-class outcome.
AB  - Biomarker signature identification in "omics" data is a complex challenge that
      requires specialized feature selection algorithms. The objective of these
      algorithms is to select the smallest set(s) of molecular quantities that are able
      to predict a given outcome (target) with maximal predictive performance. This
      task is even more challenging when the outcome comprises of multiple classes; for
      example, one may be interested in identifying the genes whose expressions allow
      discrimination among different types of cancer (nominal outcome) or among
      different stages of the same cancer, e.g. Stage 1, 2, 3 and 4 of Lung
      Adenocarcinoma (ordinal outcome). In this work, we consider a particular type of
      successful feature selection methods, named constraint-based, local causal
      discovery algorithms. These algorithms depend on performing a series of
      conditional independence tests. We extend these algorithms for the analysis of
      problems with continuous predictors and multi-class outcomes, by developing and
      equipping them with an appropriate conditional independence test procedure for
      both nominal and ordinal multi-class targets. The test is based on multinomial
      logistic regression and employs the log-likelihood ratio test for model
      selection. We present a comparative, experimental evaluation on seven real-world,
      high-dimensional, gene-expression datasets. Within the scope of our analysis the
      results indicate that the new conditional independence test allows the
      identification of smaller and better performing signatures for multi-class
      outcome datasets, with respect to the current alternatives for performing the
      independence tests. 

PMID- 24688713
TI  - Study of uremic toxin fluxes across nanofabricated hemodialysis membranes using
      irreversible thermodynamics.
AB  - INTRODUCTION: The flux of uremic toxin middle molecules through currently used
      hemodialysis membranes is suboptimal, mainly because of the membranes' pore
      architecture. AIM: Identifying the modifiable sieving parameters that can be
      improved by nanotechnology to enhance fluxes of uremic toxins across the walls of
      dialyzers' capillaries. METHODS: We determined the maximal dimensions of
      endothelin, cystatin C, and interleukin - 6 using the macromolecular modeling
      software, COOT. We also applied the expanded Nernst-Plank equation to calculate
      the changes in the overall flux as a function of increased electro-migration and
      pH of the respective molecules. RESULTS: In a high flux hemodialyzer, the
      effective diffusivities of endothelin, cystatin C, and interleukin - 6 are 15.00
      x 10(-10) cm(2)/s, 7.7 x 10(-10) cm(2)/s, and 5.4 x 10(-10) cm(2)/s,
      respectively, through the capillaries' walls. In a nanofabricated membrane, the
      effective diffusivities of endothelin, cystatin C, and interleukin - 6 are 13.87
      x 10(-7) cm(2)/s, 5.73 x 10(-7) cm(2)/s, and 3.45 x 10(-7) cm(2)/s, respectively,
      through a nanofabricated membrane. Theoretical modeling showed that a 96%
      reduction in the membrane's thickness and the application of an electric
      potential of 10 mV across the membrane could enhance the flux of endothelin,
      cystatin C, and interleukin - 6 by a factor of 25. A DeltapH of 0.07 altered the
      fluxes minimally. CONCLUSIONS: Nanofabricated hemodialysis membranes with a
      reduced thickness and an applied electric potential can enhance the effective
      diffusivity and electro-migration flux of the respective uremic toxins by 3
      orders of magnitude as compared to those passing through the high flux
      hemodialyzer.

PMID- 24688714
TI  - Meeting report: the seventh conference of the hellenic society for computational
      biology and bioinformatics.

PMID- 24688715
TI  - Searching for electrical properties, phenomena and mechanisms in the construction
      and function of chromosomes.
AB  - OUR STUDIES REVEAL PREVIOUSLY UNIDENTIFIED ELECTRICAL PROPERTIES OF CHROMOSOMES:
      (1) chromosomes are amazingly similar in construction and function to electrical
      transformers; (2) chromosomes possess in their construction and function,
      components similar to those of electric generators, conductors, condensers,
      switches, and other components of electrical circuits; (3) chromosomes
      demonstrate in nano-scale level electromagnetic interactions, resonance, fusion
      and other phenomena similar to those described by equations in classical physics.
      These electrical properties and phenomena provide a possible explanation for
      unclear and poorly understood mechanisms in clinical genetics including: (a)
      electrically based mechanisms responsible for breaks, translocations, fusions,
      and other chromosomal abnormalities associated with cancer, intellectual
      disability, infertility, pregnancy loss, Down syndrome, and other genetic
      disorders; (b) electrically based mechanisms involved in crossing over, non
      disjunction and other events during meiosis and mitosis; (c) mechanisms
      demonstrating heterochromatin to be electrically active and genetically
      important. 

PMID- 24688716
TI  - A network-based approach for predicting Hsp27 knock-out targets in mouse skeletal
      muscles.
AB  - Thanks to genomics, we have previously identified markers of beef tenderness, and
      computed a bioinformatic analysis that enabled us to build an interactome in
      which we found Hsp27 at a crucial node. Here, we have used a network-based
      approach for understanding the contribution of Hsp27 to tenderness through the
      prediction of its interactors related to tenderness. We have revealed the direct
      interactors of Hsp27. The predicted partners of Hsp27 included proteins involved
      in different functions, e.g. members of Hsp families (Hsp20, Cryab, Hsp70a1a, and
      Hsp90aa1), regulators of apoptosis (Fas, Chuk, and caspase-3), translation
      factors (Eif4E, and Eif4G1), cytoskeletal proteins (Desmin) and antioxidants
      (Sod1). The abundances of 15 proteins were quantified by Western blotting in two
      muscles of HspB1-null mice and their controls. We observed changes in the amount
      of most of the Hsp27 predicted targets in mice devoid of Hsp27 mainly in the most
      oxidative muscle. Our study demonstrates the functional links between Hsp27 and
      its predicted targets. It suggests that Hsp status, apoptotic processes and
      protection against oxidative stress are crucial for post-mortem muscle
      metabolism, subsequent proteolysis, and therefore for beef tenderness. 

PMID- 24688717
TI  - The albumin-binding domain as a scaffold for protein engineering.
AB  - The albumin-binding domain is a small, three-helical protein domain found in
      various surface proteins expressed by gram-positive bacteria. Albumin binding is
      important in bacterial pathogenesis and several homologous domains have been
      identified. Such albumin-binding regions have been used for protein purification
      or immobilization. Moreover, improvement of the pharmacokinetics, through the non
      covalent association to albumin, by fusing such domains to therapeutic proteins
      has been shown to be successful. Domains derived from streptococcal protein G and
      protein PAB from Finegoldia magna, which share a common origin and therefore
      represent an interesting evolutionary system, have been thoroughly studied
      structurally and functionally. Their albumin-binding sites have been mapped and
      these domains form the basis for a wide range of protein engineering approaches.
      By substitution-mutagenesis they have been engineered to achieve a broader
      specificity, an increased stability or an improved binding affinity,
      respectively. Furthermore, novel binding sites have been incorporated either by
      replacing the original albumin-binding surface, or by complementing it with a
      novel interaction interface. Combinatorial protein libraries, where several
      residues have been randomized simultaneously, have generated a large number of
      new variants with desired binding characteristics. The albumin-binding domain has
      also been utilized to explore the relationship between three-dimensional
      structure and amino acid sequence. Proteins with latent structural information
      built into their sequence, where a single amino acid substitution shifts the
      equilibrium in favor of a different fold with a new function, have been designed.
      Altogether, these examples illustrate the versatility of the albumin-binding
      domain as a scaffold for protein engineering. 

PMID- 24688719
TI  - Methods for recombinant expression and functional characterization of human
      cannabinoid receptor CB2.
AB  - Cannabinoid receptor CB2 is a seven transmembrane-domain integral membrane
      protein that belongs to a large superfamily of G protein-coupled receptors
      (GPCR). CB2 is a part of the endocannabinoid system that plays vital role in
      regulation of immune response, inflammation, pain sensitivity, obesity and other
      physiological responses. Information about the structure and mechanisms of
      functioning of this receptor in cell membranes is essential for the rational
      development of specific pharmaceuticals. Here we review the methodology for
      recombinant expression, purification, stabilization and biochemical
      characterization of CB2 suitable for preparation of multi-milligram quantities of
      functionally active receptor. The biotechnological protocols include expression
      of the recombinant CB2 in E. coli cells as a fusion with the maltose binding
      protein, stabilization with a high affinity ligand and a derivative of
      cholesterol in detergent micelles, efficient purification by tandem affinity
      chromatography, and reconstitution of the receptor into lipid bilayers. The
      purified recombinant CB2 receptor is amenable to functional and structural
      studies including nuclear magnetic resonance spectroscopy and a wide range of
      biochemical and biophysical techniques. 

PMID- 24688718
TI  - The essential biology of the endoplasmic reticulum stress response for structural
      and computational biologists.
AB  - The endoplasmic reticulum (ER) stress response is a cytoprotective mechanism that
      maintains homeostasis of the ER by upregulating the capacity of the ER in
      accordance with cellular demands. If the ER stress response cannot function
      correctly, because of reasons such as aging, genetic mutation or environmental
      stress, unfolded proteins accumulate in the ER and cause ER stress-induced
      apoptosis, resulting in the onset of folding diseases, including Alzheimer's
      disease and diabetes mellitus. Although the mechanism of the ER stress response
      has been analyzed extensively by biochemists, cell biologists and molecular
      biologists, many aspects remain to be elucidated. For example, it is unclear how
      sensor molecules detect ER stress, or how cells choose the two opposite cell
      fates (survival or apoptosis) during the ER stress response. To resolve these
      critical issues, structural and computational approaches will be indispensable,
      although the mechanism of the ER stress response is complicated and difficult to
      understand holistically at a glance. Here, we provide a concise introduction to
      the mammalian ER stress response for structural and computational biologists. 

PMID- 24688720
TI  - Characterization of ENU-induced Mutations in Red Blood Cell Structural Proteins.
AB  - Murine models with modified gene function as a result of N-ethyl-N-nitrosourea
      (ENU) mutagenesis have been used to study phenotypes resulting from genetic
      change. This study investigated genetic factors associated with red blood cell
      (RBC) physiology and structural integrity that may impact on blood component
      storage and transfusion outcome. Forward and reverse genetic approaches were
      employed with pedigrees of ENU-treated mice using a homozygous recessive breeding
      strategy. In a "forward genetic" approach, pedigree selection was based upon
      identification of an altered phenotype followed by exome sequencing to identify a
      causative mutation. In a second strategy, a "reverse genetic" approach based on
      selection of pedigrees with mutations in genes of interest was utilised and,
      following breeding to homozygosity, phenotype assessed. Thirty-three pedigrees
      were screened by the forward genetic approach. One pedigree demonstrated
      reticulocytosis, microcytic anaemia and thrombocytosis. Exome sequencing revealed
      a novel single nucleotide variation (SNV) in Ank1 encoding the RBC structural
      protein ankyrin-1 and the pedigree was designated Ank1(EX34). The reticulocytosis
      and microcytic anaemia observed in the Ank1(EX34) pedigree were similar to
      clinical features of hereditary spherocytosis in humans. For the reverse genetic
      approach three pedigrees with different point mutations in Spnb1 encoding RBC
      protein spectrin-1beta, and one pedigree with a mutation in Epb4.1, encoding band
      4.1 were selected for study. When bred to homozygosity two of the spectrin-1beta
      pedigrees (a, b) demonstrated increased RBC count, haemoglobin (Hb) and
      haematocrit (HCT). The third Spnb1 mutation (spectrin-1beta c) and mutation in
      Epb4.1 (band 4.1) did not significantly affect the haematological phenotype,
      despite these two mutations having a PolyPhen score predicting the mutation may
      be damaging. Exome sequencing allows rapid identification of causative mutations
      and development of databases of mutations predicted to be disruptive. These tools
      require further refinement but provide new approaches to the study of genetically
      defined changes that may impact on blood component storage and transfusion
      outcome. 

PMID- 24688721
TI  - Progression of 'OMICS' methodologies for understanding the pathogenicity of
      Corynebacterium pseudotuberculosis: the Brazilian experience.
AB  - Since the first successful attempt at sequencing the Corynebacterium
      pseudotuberculosis genome, large amounts of genomic, transcriptomic and proteomic
      data have been generated. C. pseudotuberculosis is an interesting bacterium due
      to its great zoonotic potential and because it causes considerable economic
      losses worldwide. Furthermore, different strains of C. pseudotuberculosis are
      capable of causing various diseases in different hosts. Currently, we seek
      information about the phylogenetic relationships between different strains of C.
      pseudotuberculosis isolates from different hosts across the world and to employ
      these data to develop tools to diagnose and eradicate the diseases these strains
      cause. In this review, we present the latest findings on C. pseudotuberculosis
      that have been obtained with the most advanced techniques for sequencing and
      genomic organization. We also discuss the development of in silico tools for
      processing these data to prompt a better understanding of this pathogen. 

PMID- 24688723
TI  - The Cytotoxic Effects of Low Intensity Visible and Infrared Light on Human Breast
      Cancer (MCF7) cells.
AB  - A concept of using low intensity light therapy (LILT) as an alternative approach
      to cancer treatment is at early stages of development; while the therapeutic
      effects of LILT as a non-invasive treatment modality for localized joint and soft
      tissue wound healing are widely corroborated. The LEDs-based exposure system was
      designed and constructed to irradiate the selected cancer and normal cells and
      evaluate the biological effects induced by light exposures in visible and
      infrared light range. In this study, human breast cancer (MCF7) cells and human
      epidermal melanocytes (HEM) cells (control) were exposed to selected far infrared
      light (3400nm, 3600nm, 3800nm, 3900nm, 4100nm and 4300nm) and visible and near
      infrared wavelengths (466nm, 585nm, 626nm, 810nm, 850nm and 950nm). The optical
      intensities of LEDs used for exposures were in the range of 15uW to 30uW.
      Cellular morphological changes of exposed and sham-exposed cells were evaluated
      using light microscopy. The cytotoxic effects of these low intensity light
      exposures on human cancer and normal cell lines were quantitatively determined by
      Lactate dehydrogenase (LDH) cytotoxic activity and PrestoBlueTM cell viability
      assays. Findings reveal that far-infrared exposures were able to reduce cell
      viability of MCF7 cells as measured by increased LDH release activity and
      PrestoBlueTM assays. Further investigation of the effects of light irradiation on
      different types of cancer cells, study of possible signaling pathways affected by
      electromagnetic radiation (EMR) and in vivo experimentation are required in order
      to draw a firm conclusion about the efficacy of low intensity light as an
      alternative non-invasive cancer treatment. 

PMID- 24688722
TI  - Probing Genome Maintenance Functions of human RECQ1.
AB  - The RecQ helicases are a highly conserved family of DNA-unwinding enzymes that
      play key roles in protecting the genome stability in all kingdoms of life. Human
      RecQ homologs include RECQ1, BLM, WRN, RECQ4, and RECQ5beta. Although the
      individual RecQ-related diseases are characterized by a variety of clinical
      features encompassing growth defects (Bloom Syndrome and Rothmund Thomson
      Syndrome) to premature aging (Werner Syndrome), all these patients have a high
      risk of cancer predisposition. Here, we present an overview of recent progress
      towards elucidating functions of RECQ1 helicase, the most abundant but poorly
      characterized RecQ homolog in humans. Consistent with a conserved role in genome
      stability maintenance, deficiency of RECQ1 results in elevated frequency of
      spontaneous sister chromatid exchanges, chromosomal instability, increased DNA
      damage and greater sensitivity to certain genotoxic stress. Delineating what
      aspects of RECQ1 catalytic functions contribute to the observed cellular
      phenotypes, and how this is regulated is critical to establish its biological
      functions in DNA metabolism. Recent studies have identified functional
      specialization of RECQ1 in DNA repair; however, identification of fundamental
      similarities will be just as critical in developing a unifying theme for RecQ
      actions, allowing the functions revealed from studying one homolog to be
      extrapolated and generalized to other RecQ homologs. 

PMID- 24688724
TI  - Quantitative HSQC Analyses of Lignin: A Practical Comparison.
AB  - Lignin is the second-most abundant polymer after cellulose within the biomass of
      our planet. Structurally, it displays random oligomeric units without fixed
      repetition schemes beyond the stage of dimers. Quantitative (1)H-(13)C HSQC
      measurements have recently greatly facilitated lignin analyses. In some cases,
      however, long acquisition times needed for obtaining quantitative HSQCs are not
      compatible with the chemical integrity of (a potentially functionalised) lignin
      sample. We thus compared different methods that were developed for more time
      efficient quantitative HSQC measurements with respect to their usefulness in
      lignin analyses: reliable and reproducible results were obtained using both the
      QQ-HSQC and the HSQC0 method. 

PMID- 24688725
TI  - The innovative medicines initiative: a public private partnership model to foster
      drug discovery.
AB  - The Innovative Medicines Initiative (IMI) is a large-scale public-private
      partnership between the European Commission and the European Federation of
      Pharmaceutical Industries and Associations (EFPIA). IMI aims to boost the
      development of new medicines across Europe by implementing new collaborative
      endeavours between large pharmaceutical companies and other key actors in the
      health-care ecosystem, i.e., academic institutions, small and medium enterprises,
      patients, and regulatory authorities. Currently there are more than 40 IMI
      projects covering the whole value chain of pharmaceutical R&D, but with a strong
      focus on drug discovery, as an ideal arena where the PPP concept of pre
      competitive collaboration can rapidly deliver results. This article review recent
      achievements of the IMI consortia of relevance to drug discovery, providing proof
      of-concept evidence for the efficiency of this new model of collaboration. 

PMID- 24688726
TI  - The role of Lipoxin A4 in Cystic Fibrosis Lung Disease.
AB  - In Cystic Fibrosis (CF), mutations of the CFTR gene result in defective Cl(-)
      secretion and Na(+) hyperabsorption by epithelia which leads to airway lumen
      dehydration and mucus plugging and favours chronic bacterial colonization,
      persistent inflammation and progressive lung destruction. Beyond this general
      description, the pathogenesis of CF lung disease remains obscure due to an
      incomplete understanding of normal innate airway defense. This mini-review aims
      to highlight the role of the pro-resolution lipid mediator, Lipoxin A4, which is
      inadequately produced in CF, on several aspects of innate immunity that are
      altered in CF airway disease. 

PMID- 24688727
TI  - The role of mitochondria in the development and progression of lung cancer.
AB  - The influence of mitochondria in human health and disease is a rapidly expanding
      topic in the scientific literature due to their integral roles in cellular death
      and survival. Mitochondrial biology and alterations in function were first linked
      to cancer in the 1920s with the discovery of the Warburg effect. The utilization
      of aerobic glycolysis in ATP synthesis was the first of many observations of
      metabolic reprogramming in cancer. Mitochondrial dysfunction in cancer has
      expanded to include defects in mitochondrial genomics and biogenesis, apoptotic
      signaling and mitochondrial dynamics. This review will focus on the role of
      mitochondria and their influence on cancer initiation, progression and treatment
      in the lung. 

PMID- 24688729
TI  - Bile acid binding protein: a versatile host of small hydrophobic ligands for
      applications in the fields of MRI contrast agents and bio-nanomaterials.
AB  - During the last decade a growing amount of evidence has been obtained, supporting
      the role of the beta-clamshell family of intracellular lipid binding proteins
      (iLBPs) not only in the translocation of lipophilic molecules but also in lipid
      mediated signalling and metabolism. Given the central role of lipids in
      physiological processes, it is essential to have detailed knowledge on their
      interactions with cognate binding proteins. Structural and dynamical aspects of
      the binding mechanisms have been widely investigated by means of NMR
      spectroscopy, docking and molecular dynamics simulation approaches. iLBPs share a
      stable beta-barrel fold, delimiting an internal cavity capable of promiscuous
      ligand binding and display significant flexibility at the putative ligand portal.
      These features make this class of proteins good scaffolds to build host-guest
      systems for applications in nanomedicine and nanomaterials. 

PMID- 24688728
TI  - The Role of INDY in Metabolic Regulation.
AB  - Reduced expression of the Indy (I'm Not Dead Yet) gene in D. melanogaster and C.
      elegans extends longevity. Indy and its mammalian homolog mINDY (Slc 3a5, NaCT)
      are transporters of TCA cycle intermediates, mainly handling the uptake of
      citrate via the plasma membrane into the cytosol. Deletion of mINDY in mice leads
      to significant metabolic changes akin to caloric restriction, likely caused by
      reducing the effects of mINDY-imported citrate on fatty acid and cholesterol
      synthesis, glucose metabolism and beta-oxidation. This review will provide an
      overview on different mammalian SLC 3 family members with a focus on mINDY (SLC
      3A5) in glucose and energy metabolism and will highlight the role of mINDY as a
      putative therapeutic target for the treatment of obesity, non-alcoholic fatty
      liver disease and type 2 diabetes. 

PMID- 24688730
TI  - Of mice and men: Dissecting the interaction between Listeria monocytogenes
      Internalin A and E-cadherin.
AB  - We report a study of the interaction between internalin A (inlA) and human or
      murine E-cadherin (Ecad). inlA is used by Listeria monocytogenes to internalize
      itself into host cell, but the bacterium is unable to invade murine cells, which
      has been attributed to the difference in sequence between hEcad and mEcad. Using
      molecular dynamics simulations, MM/GBSA free energy calculations, hydrogen bond
      analysis, water characterization and umbrella sampling, we provide a complete
      atomistic picture of the binding between inlA and Ecad. We dissect key residues
      in the protein-protein interface and analyze the energetics using MM/GBSA. From
      this analysis it is clear that the binding of inlA-mEcad is weaker than inlA
      hEcad, on par with the experimentally observed inability of inlA to bind to
      mEcad. However, extended MD simulations of 200 ns in length show no
      destabilization of the inlA-mEcad complex and the estimation of the potential of
      mean force (PMF) using umbrella sampling corroborates this conclusion. The
      binding strength computed from the PMFs show no significant difference between
      the two protein complexes. Hence, our study suggests that the inability of L.
      monocytogenes to invade murine cells cannot be explained by processes at the
      nanosecond to sub-microsecond time scale probed by the simulations performed
      here. 

PMID- 24688732
TI  - A Two-stage Peak Alignment Algorithm for Two-Dimensional Gas Chromatography Time
      of-Flight Mass Spectrometry-Based Metabolomics.
AB  - Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass
      spectrometry (GC*GC/TOF-MS) has been applied to metabolomics analyses recently.
      However, retention time shifts in the two-dimensional gas chromatography will
      introduce difficulty to compare compound profiles obtained from multiple samples.
      In this work, a novel two-stage peak alignment algorithm has been developed for
      data analysis of GC*GC/TOF-MS. In the first stage, our algorithm detects and
      merges multiple peak entries of the same metabolite into one peak entry. After a
      z-score transformation of metabolite retention times, landmark peaks will be
      selected from all samples based on both two-dimensional retention times and mass
      spectrum similarity of fragment ions measured by Pearson's correlation
      coefficient. In the second stage, the original two-dimensional retention time
      shift will be corrected using a local linear fitting method. A progressive
      retention time map searching method is used to align peaks in all samples
      together based on the parameters optimized in the first stage. Our algorithm can
      avoid defining a threshold of retention time window and spectrum similarity,
      which is very difficult for the users since the experimental condition is always
      changed in different experimental runs, even for the repeat experiments. The
      experimental results show that our algorithm can work well in peak alignment from
      real biological samples, which is very important for the further analysis. 

PMID- 24688731
TI  - Changes in the genome-wide localization pattern of Sir3 in Saccharomyces
      cerevisiae during different growth stages.
AB  - In budding yeast, the Sir2, Sir3 and Sir4 proteins form SIR complexes, required
      for the assembly of silent heterochromatin domains, and which mediate
      transcription silencing at the telomeres as well as at silent mating type loci.
      In this study, under fluorescence microscopy, we found most Sir3-GFP expressions
      in the logarithmic phase cells appeared as multiple punctations as expected.
      However, some differences in the distribution of fluorescent signals were
      detected in the diauxic~early stationary phase cells. To clarify these, we then
      used ChIP on chip assays to investigate the genome-wide localization of Sir3. In
      general, Sir3 binds to all 32 telomere proximal regions, the silent mating type
      loci and also binds to the rDNA region. However, the genome-wide localization
      patterns of Sir3 are different between these two distinct growth phases. We also
      confirmed that Sir3 binds to a recently identified secondary binding site, PAU
      genes, and further identified 349 Sir3-associated cluster regions. These results
      provide additional support in roles for Sir3 in the modulation of gene expression
      during physical conditions such as diauxic~early stationary phase growing.
      Moreover, they imply that Sir3 may be not only involved in the formation of
      conventional silent heterochromatin, but also able to associate with some other
      chromatin regions involved in epigenetic regulation. 

PMID- 24688733
TI  - The biological microprocessor, or how to build a computer with biological parts.
AB  - Systemics, a revolutionary paradigm shift in scientific thinking, with
      applications in systems biology, and synthetic biology, have led to the idea of
      using silicon computers and their engineering principles as a blueprint for the
      engineering of a similar machine made from biological parts. Here we describe
      these building blocks and how they can be assembled to a general purpose computer
      system, a biological microprocessor. Such a system consists of biological parts
      building an input / output device, an arithmetic logic unit, a control unit,
      memory, and wires (busses) to interconnect these components. A biocomputer can be
      used to monitor and control a biological system. 

PMID- 24688734
TI  - A network view on Parkinson's disease.
AB  - Network-based systems biology tools including Pathway Studio 9.0 were used to
      identify Parkinson's disease (PD) critical molecular players, drug targets, and
      underlying biological processes. Utilizing several microarray gene expression
      datasets, biomolecular networks such as direct interaction, shortest path, and
      microRNA regulatory networks were constructed and analyzed for the disease
      conditions. Network topology analysis of node connectivity and centrality
      revealed in combination with the guilt-by-association rule 17 novel genes of PD
      potential interest. Seven new microRNAs (miR-132, miR-133a1, miR-181-1, miR-182,
      miR-218-1, miR-29a, and miR-330) related to Parkinson's disease were identified,
      along with more microRNA targeted genes of interest like RIMS3, SEMA6D and SYNJ1.
      David and IPA enrichment analysis of KEGG and canonical pathways provided
      valuable mechanistic information emphasizing among others the role of chemokine
      signaling, adherence junction, and regulation of actin cytoskeleton pathways.
      Several routes for possible disease initiation and neuro protection mechanisms
      triggered via the extra-cellular ligands such as CX3CL1, SEMA6D and IL12B were
      thus uncovered, and a dual regulatory system of integrated transcription factors
      and microRNAs mechanisms was detected. 

PMID- 24688735
TI  - Therapeutic application of nanotechnology in cardiovascular and pulmonary
      regeneration.
AB  - Recently, a wide range of nanotechnologies has been approached for material
      modification by realizing the fact that the extracellular matrix (ECM) consists
      of nanoscale components and exhibits nanoscale architectures. Moreover, cell-cell
      and cell- ECM interactions actively occur on the nanoscale and ultimately play
      large roles in determining cell fate in tissue engineering. Nanomaterials have
      provided the potential to preferentially control the behavior and differentiation
      of cells. The present paper reviews the need for nanotechnology in regenerative
      medicine and the role of nanotechnology in repairing, restoring, and regenerating
      damaged body parts, such as blood vessels, lungs, and the heart. 

PMID- 24688736
TI  - Biochemical and biophysical characterization of recombinant yeast proteasome
      maturation factor ump1.
AB  - Protein degradation is essential for maintaining cellular homeostasis. The
      proteasome is the central enzyme responsible for non-lysosomal protein
      degradation in eukaryotic cells. Although proteasome assembly is not yet
      completely understood, a number of cofactors required for proper assembly and
      maturation have been identified. Ump is a short-lived maturation factor required
      for the efficient biogenesis of the 20S proteasome. Upon the association of the
      two precursor complexes, Ump is encased and is rapidly degraded after the
      proteolytic sites in the interior of the nascent proteasome are activated. In
      order to further understand the mechanisms behind proteasomal maturation, we
      expressed and purified yeast Ump in E. coli for biophysical and structural
      analysis. We show that recombinant Ump is purified as a mixture of different
      oligomeric species and that oligomerization is mediated by intermolecular
      disulfide bond formation involving the only cysteine residue present in the
      protein. Furthermore, a combination of bioinformatic, biochemical and structural
      analysis revealed that Ump shows characteristics of an intrinsically disordered
      protein, which might become structured only upon interaction with the proteasome
      subunits. 

PMID- 24688738
TI  - Robustness in experimental design: A study on the reliability of selection
      approaches.
AB  - The quality criteria for experimental design approaches in chemoinformatics are
      numerous. Not only the error performance of a model resulting from the selected
      compounds is of importance, but also reliability, consistency, stability and
      robustness against small variations in the dataset or structurally diverse
      compounds. We developed a new stepwise, adaptive approach, DescRep, combining an
      iteratively refined descriptor selection with a sampling based on the putatively
      most representative compounds. A comparison of the proposed strategy was based on
      statistical performance of models derived from such a selection to those derived
      by other popular and frequently used approaches, such as the Kennard-Stone
      algorithm or the most descriptive compound selection. We used three datasets to
      carry out a statistical evaluation of the performance, reliability and robustness
      of the resulting models. Our results indicate that stepwise and adaptive
      approaches have a better adaptability to changes within a dataset and that this
      adaptability results in a better error performance and stability of the resulting
      models. 

PMID- 24688737
TI  - A method to predict edge strands in beta-sheets from protein sequences.
AB  - There is a need for rules allowing three-dimensional structure information to be
      derived from protein sequences. In this work, consideration of an elementary
      protein folding step allows protein sub-sequences which optimize folding to be
      derived for any given protein sequence. Classical mechanics applied to this
      system and the energy conservation law during the elementary folding step yields
      an equation whose solutions are taken over the field of rational numbers. This
      formalism is applied to beta-sheets containing two edge strands and at least two
      central strands. The number of protein sub-sequences optimized for folding per
      amino acid in beta-strands is shown in particular to predict edge strands from
      protein sequences. Topological information on beta-strands and loops connecting
      them is derived for protein sequences with a prediction accuracy of 75%. The
      statistical significance of the finding is given. Applications in protein
      structure prediction are envisioned such as for the quality assessment of protein
      structure models. 

PMID- 24688739
TI  - Three-dimensional mapping of differential amino acids of human, murine, canine
      and equine TLR4/MD-2 receptor complexes conferring endotoxic activation by lipid
      A, antagonism by Eritoran and species-dependent activities of Lipid IVA in the
      mammalian LPS sensor system.
AB  - A literature review concerning the unexpected species differences of the
      vertebrate innate immune response to lipid IVA was published in CSBJ prior to the
      present computational study to address the unpaired activity-sequence correlation
      of prototypic E. coli -type lipid A and its precursor lipid IVA regarding human,
      murine, equine and canine species. To this end, their sequences and structures of
      hitherto known Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2
      (MD-2) complexes were aligned and their differential side chain patterns studied.
      If required due to the lack of the corresponding X-ray crystallographic data,
      three-dimensional models of TLR4/MD-2/ligand complexes were generated using mono
      and dimeric crystal structures as templates and in silico docking of the
      prototypic ligands lipid A, lipid IVA and Eritoran. All differential amino acids
      were mapped to pinpoint species dependency on an atomic scale, i.e. the possible
      concert of mechanistically relevant side chains. In its most abstract and general
      form the three-dimensional (3D-) models devise a triangular interface or "wedge"
      where molecular interactions between TLR4, MD-2 and ligand itself take place.
      This study identifies two areas in the wedge related to either agonism or
      antagonism reflecting why ligands like lipid IVA can possess a species dependent
      dual activity. Lipid IVA represents an imperfect (underacylated and backbone
      flipped), low affinity ligand of mammalian TLR4/MD-2 complexes. Its specific but
      weak antagonistic activity in the human system is in particular due to the loss
      of phosphate attraction in the wedge-shaped region conferred by nonhomologous
      residue changes when compared to crystal and modeled structures of the
      corresponding murine and equine TLR4/MD-2 complexes. The counter-TLR4/MD-2 unit
      was also taken into account since agonist-mediated dimerization in a defined m
      shaped complex composed of two TLR4/MD-2/agonist subunits triggers intracellular
      signaling during the innate immune response to bacterial endotoxin exposure. 

PMID- 24688740
TI  - From plant genomes to protein families: computational tools.
AB  - The development of new high-throughput sequencing technologies has increased
      dramatically the number of successful genomic projects. Thus, draft genomic
      sequences of more than 60 plant species are currently available. Suitable
      bioinformatics tools are being developed to assemble, annotate and analyze the
      enormous number of sequences produced. In this context, specific plant
      comparative genomic databases are become powerful tools for gene family
      annotation in plant clades. In this mini-review, the current state-of-art of
      genomic projects is glossed. Besides, the computational tools developed to
      compare genomic data are compiled. 

PMID- 24688741
TI  - Frequency of dipeptides and antidipeptides.
AB  - Although it is reasonable to expect that the frequency of a generic dipeptide XY
      in proteins is the same of its counterpart YX, on the basis of an accurate
      statistical analysis of a large number of protein sequences, it appears that some
      dipeptides XY are considerably more frequent than their mirror images YX,
      referred to as antidipeptides. Given that it has been verified that this
      unexpected anisotropic frequency of occurrence is unbiased by the type of protein
      sequences that are analyzed, it is possible to conclude that this is a genuine
      phenomenon. Nevertheless, it was impossible to find the mechanism underlying this
      unexpected phenomenon, which does not seem to be related to diverse
      conformational propensities, to the different conformational flexibility of the
      peptide/antidipeptide pair, to dissimilar accessibility to the solvent or to gene
      random mutations. 

PMID- 24688742
TI  - Autophagy in Plasmodium, a multifunctional pathway?
AB  - Autophagy is a catabolic process that normally utilizes the lysosome. The far
      reaching implications of this system in disease are being increasingly
      understood. Studying autophagy is complicated by its role in cell survival and
      programmed cell death and the involvement of the canonical marker of autophagy,
      Atg8/LC3, in numerous non-autophagic roles. The malaria parasite, Plasmodium, has
      conserved certain aspects of the autophagic machinery but for what purpose has
      long remained a mystery. Major advances have recently been gained and suggest a
      role for Atg8 in apicoplast maintenance, degradation of heme inside the food
      vacuole, and possibly trafficking of proteins or organelles outside the parasite
      membrane. Autophagy may also participate in programmed cell death under drug
      treatment or as a selective tool to limit parasite load. We review the current
      findings and discuss discrepancies in the field of autophagy in the Plasmodium
      parasite. 

PMID- 24688743
TI  - A Sieve-Raft Hypothesis for the regulation of endothelial fenestrations.

PMID- 24688745
TI  - Structure-based Methods for Computational Protein Functional Site Prediction.
AB  - Due to the advent of high throughput sequencing techniques and structural genomic
      projects, the number of gene and protein sequences has been ever increasing.
      Computational methods to annotate these genes and proteins are even more
      indispensable. Proteins are important macromolecules and study of the function of
      proteins is an important problem in structural bioinformatics. This paper
      discusses a number of methods to predict protein functional site especially
      focusing on protein ligand binding site prediction. Initially, a short overview
      is presented on recent advances in methods for selection of homologous sequences.
      Furthermore, a few recent structural based approaches and sequence-and-structure
      based approaches for protein functional sites are discussed in details. 

PMID- 24688744
TI  - Inverted topologies in membrane proteins: a mini-review.
AB  - Helical membrane proteins such as transporters, receptors, or channels often
      exhibit structural symmetry. Symmetry is perfect in homo-oligomers consisting of
      two or more copies of the same protein chain. Intriguingly, in single chain
      membrane proteins, often internal pseudo-symmetry is observed, in particular in
      transporters and channels. In several cases single chain proteins with pseudo
      symmetry exist, that share the fold with homo-oligomers suggesting evolutionary
      pathways that involve gene duplication and fusion. It has been hypothesized that
      such evolutionary pathways allow for the rapid development of large proteins with
      novel functionality. At the same time symmetry can be leveraged to recognize
      highly symmetric substrates such as ions. Here we review helical transporter
      proteins with an inverted two-fold pseudo-symmetry. In this special scenario the
      symmetry axis lies in the membrane plane. As a result, the putative ancestral
      monomeric protein would insert in both directions into the membrane and its open
      to-the-inside and open-to-the-outside conformations would be structurally
      identical and iso-energetic, giving a possible evolutionary pathway to create a
      transporter protein that needs to flip between the two states. 

PMID- 24688746
TI  - Reconstruction of SAXS Profiles from Protein Structures.
AB  - Small angle X-ray scattering (SAXS) is used for low resolution structural
      characterization of proteins often in combination with other experimental
      techniques. After briefly reviewing the theory of SAXS we discuss computational
      methods based on 1) the Debye equation and 2) Spherical Harmonics to compute
      intensity profiles from a particular macromolecular structure. Further, we review
      how these formulas are parameterized for solvent density and hydration shell
      adjustment. Finally we introduce our solution to compute SAXS profiles utilizing
      GPU acceleration. 

PMID- 24688747
TI  - Recent advances in functional region prediction by using structural and
      evolutionary information - Remaining problems and future extensions.
AB  - Structural genomics projects have solved many new structures with unknown
      functions. One strategy to investigate the function of a structure is to
      computationally find the functionally important residues or regions on it.
      Therefore, the development of functional region prediction methods has become an
      important research subject. An effective approach is to use a method employing
      structural and evolutionary information, such as the evolutionary trace (ET)
      method. ET ranks the residues of a protein structure by calculating the scores
      for relative evolutionary importance, and locates functionally important sites by
      identifying spatial clusters of highly ranked residues. After ET was developed,
      numerous ET-like methods were subsequently reported, and many of them are in
      practical use, although they require certain conditions. In this mini review, we
      first introduce the remaining problems and the recent improvements in the methods
      using structural and evolutionary information. We then summarize the recent
      developments of the methods. Finally, we conclude by describing possible
      extensions of the evolution- and structure-based methods. 

PMID- 24688748
TI  - Measuring the shapes of macromolecules - and why it matters.
AB  - The molecular basis of life rests on the activity of biological macromolecules,
      mostly nucleic acids and proteins. A perhaps surprising finding that crystallized
      over the last handful of decades is that geometric reasoning plays a major role
      in our attempt to understand these activities. In this paper, we address this
      connection between geometry and biology, focusing on methods for measuring and
      characterizing the shapes of macromolecules. We briefly review existing numerical
      and analytical approaches that solve these problems. We cover in more details our
      own work in this field, focusing on the alpha shape theory as it provides a
      unifying mathematical framework that enable the analytical calculations of the
      surface area and volume of a macromolecule represented as a union of balls, the
      detection of pockets and cavities in the molecule, and the quantification of
      contacts between the atomic balls. We have shown that each of these quantities
      can be related to physical properties of the molecule under study and ultimately
      provides insight on its activity. We conclude with a brief description of new
      challenges for the alpha shape theory in modern structural biology. 

PMID- 24688749
TI  - Regulation of gene expression in the genomic context.
AB  - Metazoan life is dependent on the proper temporal and spatial control of gene
      expression within the many cells-essentially all with the identical genome-that
      make up the organism. While much is understood about how individual gene
      regulatory elements function, many questions remain about how they interact to
      maintain correct regulation globally throughout the genome. In this review we
      summarize the basic features and functions of the crucial regulatory elements
      promoters, enhancers, and insulators and discuss some of the ways in which proper
      interactions between these elements is realized. We focus in particular on the
      role of core promoter sequences and propose explanations for some of the
      contradictory results seen in experiments aimed at understanding insulator
      function. We suggest that gene regulation depends on local genomic context and
      argue that more holistic in vivo investigations that take into account multiple
      local features will be necessary to understand how genome-wide gene regulation is
      maintained. 

PMID- 24688751
TI  - Exploring compound promiscuity patterns and multi-target activity spaces.
AB  - Compound promiscuity is rationalized as the specific interaction of a small
      molecule with multiple biological targets (as opposed to non-specific binding
      events) and represents the molecular basis of polypharmacology, an emerging theme
      in drug discovery and chemical biology. This concise review focuses on recent
      studies that have provided a detailed picture of the degree of promiscuity among
      different categories of small molecules. In addition, an exemplary computational
      approach is discussed that is designed to navigate multi-target activity spaces
      populated with various compounds. 

PMID- 24688750
TI  - Leveraging biological replicates to improve analysis in ChIP-seq experiments.
AB  - ChIP-seq experiments identify genome-wide profiles of DNA-binding molecules
      including transcription factors, enzymes and epigenetic marks. Biological
      replicates are critical for reliable site discovery and are required for the
      deposition of data in the ENCODE and modENCODE projects. While early reports
      suggested two replicates were sufficient, the widespread application of the
      technique has led to emerging consensus that the technique is noisy and that
      increasing replication may be worthwhile. Additional biological replicates also
      allow for quantitative assessment of differences between conditions. To date it
      has remained controversial about how to confirm peak identification and to
      determine signal strength across biological replicates, particularly when the
      number of replicates is greater than two. Using objective metrics, we evaluate
      the consistency of biological replicates in ChIP-seq experiments with more than
      two replicates. We compare several approaches for binding site determination,
      including two popular but disparate peak callers, CisGenome and MACS2. Here we
      propose read coverage as a quantitative measurement of signal strength for
      estimating sample concordance. Determining binding based on genomic features,
      such as promoters, is also examined. We find that increasing the number of
      biological replicates increases the reliability of peak identification.
      Critically, binding sites with strong biological evidence may be missed if
      researchers rely on only two biological replicates. When more than two replicates
      are performed, a simple majority rule (>50% of samples identify a peak)
      identifies peaks more reliably in all biological replicates than the absolute
      concordance of peak identification between any two replicates, further
      demonstrating the utility of increasing replicate numbers in ChIP-seq
      experiments. 

PMID- 24688752
TI  - Outcomes of patients with myelodysplatic syndrome and chronic myelomonocytic
      leukemia post clofarabine failure.
AB  - BACKGROUND: The outcome of patients with myelodysplastic syndrome (MDS) and
      chronic myelomonocytic leukemia (CMML) post clofarabine is unknown. METHODS: We
      reviewed 109 patients with MDS or CMML with a median age of 67 years, treated
      with a clofarabine-based chemotherapy as frontline (n = 38) or salvage (n = 71)
      therapy. A total of 58 (53%) patients received salvage therapy after clofarabine
      failure: 13 allogeneic stem cell transplant (ASCT), 18 high-dose cytarabine
      containing regimen, 10 hypomethylating agents and 17 investigational treatments.
      RESULTS: Eight patients achieved complete remission (CR) and three had stable
      disease for an overall response rate of 19%. With a median follow-up of 3 months
      from clofarabine failure, 12 patients (11%) remained alive, 5 remain in CR, 4 of
      them after ASCT. The median overall survival post clofarabine failure was 4
      months with a 1-year survival rate of 23%. CONCLUSIONS: This outcome is
      predictable, with patients with high-risk disease at the time of clofarabine
      failure having the worse survival. To date, patients with MDS continue to have a
      short survival after failure of all available therapies. Ultimately, patients who
      are candidates for additional treatments should be offered novel approaches. In
      conclusion, the outcome of patients with MDS and CMML post clofarabine failure is
      poor. The pattern is similar to patients with MDS post hypomethylating agent
      failure and predictable using University of Texas M. D. Anderson Cancer Center
      global scoring system.

PMID- 24688754
TI  - Experience with intravenous ferric carboxymaltose in patients with iron
      deficiency anemia.
AB  - Erythropoiesis may be limited by absolute or functional iron deficiency or when
      chronic inflammatory conditions lead to iron sequestration. Intravenous iron may
      be indicated when oral iron cannot address the deficiency. Ferric carboxymaltose
      (FCM) is a nondextran iron preparation recently approved in the United States for
      intravenous treatment of iron deficiency anemia (IDA) in adult patients with
      intolerance or unsatisfactory response to oral iron or with nondialysis-dependent
      chronic kidney disease. The full dose is two administrations of up to 750 mg
      separated by at least 7 days (up to 1500 mg total). FCM can be injected in 7-8
      min or diluted in saline for slower infusion. The efficacy and safety of this
      dose was established in two prospective trials that randomized over 3500
      subjects, 1775 of whom received FCM. One trial showed similar efficacy of FCM to
      an approved intravenous iron regimen (1000 mg of iron sucrose) in 2500 subjects
      with chronic kidney disease and additional cardiovascular risk factors. The other
      trial showed superior efficacy of FCM to oral iron in subjects with IDA due to
      various etiologies (e.g. gastrointestinal or uterine bleeding). In these trials,
      there was no significant difference between FCM and comparator with respect to an
      independently adjudicated composite safety endpoint, including death, myocardial
      infarction, or stroke. A database of 5799 subjects exposed to FCM provided a
      safety profile acceptable for regulatory approval. Mechanistic studies
      demonstrated that the transient, asymptomatic reduction in serum phosphate
      observed following FCM administration results from induction of fibroblast growth
      factor 23, which in turn induces renal phosphate excretion. An elevated hepcidin
      level may identify patients with IDA who will not respond to oral iron but will
      respond to FCM. The ability to administer FCM in two rapid injections or
      infusions will likely be viewed favorably by patients and healthcare providers. 

PMID- 24688753
TI  - The evolution of clonality testing in the diagnosis and monitoring of
      hematological malignancies.
AB  - Currently, distinguishing between benign and malignant lymphoid proliferations is
      based on a combination of clinical characteristics, cyto/histomorphology,
      immunophenotype and the identification of well-defined chromosomal aberrations.
      However, such diagnoses remain challenging in 10-15% of cases of
      lymphoproliferative disorders, and clonality assessments are often required to
      confirm diagnostic suspicions. In recent years, the development of new techniques
      for clonality detection has allowed researchers to better characterize, classify
      and monitor hematological neoplasms. In the past, clonality was primarily studied
      by performing Southern blotting analyses to characterize rearrangements in
      segments of the IG and TCR genes. Currently, the most commonly used method in the
      clinical molecular diagnostic laboratory is polymerase chain reaction (PCR),
      which is an extremely sensitive technique for detecting nucleic acids. This
      technique is rapid, accurate, specific, and sensitive, and it can be used to
      analyze small biopsies as well as formalin-fixed paraffin-embedded samples. These
      advantages make PCR-based approaches the current gold standard for IG/TCR
      clonality testing. Since the completion of the first human genome sequence, there
      has been a rapid development of technologies to facilitate high-throughput
      sequencing of DNA. These techniques have been applied to the deep
      characterization and classification of various diseases, patient stratification,
      and the monitoring of minimal residual disease. Furthermore, these novel
      approaches have the potential to significantly improve the sensitivity and cost
      of clonality assays and post-treatment monitoring of B- and T-cell malignancies.
      However, more studies will be required to demonstrate the utility, sensitivity,
      and benefits of these methods in order to warrant their adoption into clinical
      practice. In this review, recent developments in clonality testing are examined
      with an emphasis on highly sensitive systems for improving diagnostic workups and
      minimal residual disease assessments. 

PMID- 24688756
TI  - The elusive link between language control and executive control: A case of
      limited transfer.
AB  - We investigated the relationship between language control and executive control
      by testing three groups of bilinguals (104 participants) and 54 monolinguals in a
      training and transfer paradigm. Participants practiced either a language or a non
      linguistic color/shape switching task and were tested one week later on both
      tasks. The color-shape task produced significant immediate improvement with
      training, which was maintained a week later, but exhibited no cross-task transfer
      effects. In the dominant-language, training effects did not persist after one
      week, and there were no transfer effects. In the non-dominant language there were
      significant training effects that lasted a week, and there was also transfer
      facilitation from prior practice with the color/shape task, which was limited to
      a reduction in mixing costs. Despite limited transfer, there were significant
      correlations between tasks in mixing costs for bilinguals, in switching costs for
      monolinguals, and in intrusion errors for all participants. Finally, the pattern
      of costs observed for the two tasks exhibited both similarities and differences
      across participants. These results imply a limited but significant role for
      executive control in bilingual language control, possibly playing a stronger role
      in facilitating non-dominant language production and in supporting the ability to
      monitor response outcomes to avoid errors.

PMID- 24688757
TI  - Adherence of antidepressants during pregnancy: MEMS compared with three other
      methods.
AB  - BACKGROUND: Data about adherence of antidepressants during pregnancy are lacking.
      However, it is important to gain insight into adherence in this population to
      reduce perinatal risks for relapse of depression. OBJECTIVE: The objective of
      this study was to search for an inexpensive and easy method to implement daily
      for assessing medication adherence during pregnancy. METHODS: An observational
      study was conducted to measure adherence by comparing pill count, Beliefs about
      Medicine questionnaire (BMQ) and blood level monitoring against the standard, the
      Medication Event Monitoring System (MEMS). We used a logistic regression model to
      determine potential predictors for poor adherence (age, marital class, highest
      level of education, monthly net income, employment, smoking, alcohol use and type
      of antidepressant). RESULTS: From January 2010 until January 2012, 41 women were
      included within the first trimester of pregnancy; data could be evaluated in 29
      women. Using MEMS, 86% of the women took in more than 80% of all prescribed doses
      on time and could be classified as adherent. Pill counts showed good agreement
      with MEMS. We did not find predictors for poor adherence in our study population.
      CONCLUSION: Adherence of antidepressants during pregnancy using MEMS is 86%.
      There was a good agreement between MEMS and pill counts. This method may serve as
      a good alternative that can be easily implemented into daily practice.

PMID- 24688758
TI  - De Novo delayed onset hypothermia secondary to therapeutic doses of risperidone
      in bipolar affective disorder.
AB  - The commonly reported side effects related to risperidone include dizziness,
      nausea, weight gain, sleep disturbances, and sexual dysfunction. A rather rare
      and very much less documented side effect of risperidone is hypothermia:
      traditionally defined as a drop in core body temperature below 35 degrees C (95
      degrees F). We report a case of a 75-year-old woman who had been treated for
      bipolar affective disorder for nearly 3 years with risperidone went on to develop
      hypothermia which was reversed with the withdrawal of the offending drug. This
      case is unique as it reported a rare but potentially serious side effect
      occurring after a prolonged administration of risperidone contrary to the
      previous reports in which hypothermia occurred only a few hours or days after the
      administration of risperidone and occurred in a patient who was diagnosed as
      having bipolar affective disorder as opposed to schizophrenia, the most common
      psychiatric disorder associated with previously reported hypothermia. The authors
      would like to emphasize the importance of this idiosyncratic potentially life
      threatening adverse effect of risperidone-induced hypothermia to all clinicians,
      which occurs regardless of the duration of drug intake, in order to help them
      identify the condition early and treat it effectively. 

PMID- 24688760
TI  - Gabapentin pharmacotherapy for antipsychotic-induced akathisia: single-patient
      experiment and case report.
AB  - This clinical study reports upon the efficacy of gabapentin (Neurontin) for
      treating severe akathisia (3 on the Barnes Akathisia Rating Scale) in two
      patients receiving quetiapine (Seroquel), one of whom also received olanzapine
      (Zyprexa) for a short period. The first patient participated in an open-label
      experiment in which the bedtime dose of gabapentin was discontinued three times
      at intervals 1 week apart, resulting in severe akathisia which was quickly
      terminated by taking his usual 1200 mg gabapentin dose. This patient was also
      taking high doses of two benzodiazepines and a beta blocker, without therapeutic
      effect upon his akathisia; only gabapentin was efficacious. The second case is a
      report of a woman taking a high dose of quetiapine for anxiety who experienced
      severe akathisia which was relieved by taking 1200 mg of gabapentin. Possible
      mechanisms of action of gabapentin are discussed. Particular attention is drawn
      to the difference between neuroleptic-induced akathisia and the neurological
      condition of restless legs syndrome. 

PMID- 24688759
TI  - Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions,
      and a systematic review and meta-analysis of efficacy.
AB  - The burden of depressive disorders and the frequent inadequacy of their current
      pharmacological treatments are well established. The anaesthetic and
      hallucinogenic drug ketamine has provoked much interest over the past decade or
      so as an extremely rapidly acting antidepressant that does not modify 'classical'
      monoaminergic receptors. Current evidence has shown several ways through which it
      might exert therapeutic antidepressant actions: blockade of glutamatergic NMDA
      receptors and relative upregulation of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) subtypes may alter cortical connectivity patterns;
      through intracellular changes in protein expression, including the proteins
      mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor
      (BDNF); and alteration of intracellular signalling cascades. The clinical
      evidence demonstrates rapid improvements in mood and suicidal thinking in most
      participants, although study numbers have generally been small and many trials
      are unblinded and methodologically weak. There is a small body of work to suggest
      ketamine might also augment electroconvulsive therapy and potentially have a role
      as a surgical anaesthetic in depressed patients. A major problem is that the
      effects of ketamine appear temporary, disappearing after days to weeks (although
      longer benefits have been sustained in some), and attempts to circumvent this
      through pharmacological augmentation have been disappointing thus far. These
      exciting data are providing new insights into neurobiological models of
      depression, and potentially opening up a new class of antidepressants, but there
      are significant practical and ethical issues about any future mainstream clinical
      role it might have. 

PMID- 24688761
TI  - Pseudohypoaldosteronism in a neonate presenting as life-threatening arrhythmia.
AB  - Neonatal hyperkalemia and hyponatremia are medical conditions that require an
      emergent diagnosis and treatment to avoid morbidity and mortality. Here, we
      describe the case of a 10-day-old female baby presenting with life-threatening
      hyperkalemia, hyponatremia, and metabolic acidosis diagnosed as autosomal
      dominant pseudohypoaldosteronism type 1 (PHA1). This report aims to recognize
      that PHA1 may present with a life-threatening arrhythmia due to severe
      hyperkalemia and describes the management of such cases in neonates. LEARNING
      POINTS: PHA1 may present with a life-threatening arrhythmia.Presentation of PHA
      can be confused with congenital adrenal hyperplasia.Timing and appropriate
      medical management in the critical care unit prevented fatality from severe
      neonatal PHA.

PMID- 24688762
TI  - Spectrum of viral infections in patients with cystic fibrosis.
AB  - This review explores the extensive influence of viral infections leading to
      chronic deterioration of lung function in patients with cystic fibrosis (CF). The
      mechanisms how viral agents affect the pathogenesis as well as the inflammatory
      and immune response of CF are discussed. Viral infections of the upper and lower
      respiratory tract due to viruses in CF patients and methods for diagnosis of
      respiratory viruses are described in detail. The importance of respiratory and
      non-respiratory viral agents for the pathogenesis, especially for the
      exacerbation of bacterial lower respiratory tract infections and course of CF, is
      stressed, especially emphasizing respiratory syncytial virus, influenza virus,
      rhinovirus, and human herpes viruses. Possible harmful effects of further viruses
      like adenovirus, bocavirus, coronavirus, metapneumovirus, parainfluenzavirus on
      the lung function of CF patients are discussed. The potential use of adenovirus
      based vectors for somatic gene therapy is mentioned. 

PMID- 24688764
TI  - The synthetic hydroxyproline-containing collagen analogue (Gly-Pro-Hyp)10
      promotes enzymatic activity of matrixmetalloproteinase-2 in vitro.
AB  - Diseases such as liver fibrosis and intestinal inflammation are characterized by
      accumulated components of the extracellular matrix (ECM). Given that fibrillar
      collagen structures were shown to serve as storage site for inactive proforms of
      matrixmetalloproteinases (MMPs), modulating this MMP-collagen interaction might
      offer a rational interventional (therapeutic) approach to enhance degradation of
      accumulated ECM. The synthetic triple helical collagen analogue (Gly-Pro-Hyp)10 -
      (GPO)10 - was shown to trigger release and enzymatic activation of collagen
      sequestered proMMP-2. In the presented study, we, for the first time,
      investigated how MMP-(GPO)10 interaction impacts cellular responses in vitro. We
      found that recombinant proMMP-2 induced proliferation of hepatic stellate cells
      (HSC), which was enhanced after addition of (GPO)10 reaching comparable levels
      following incubation with fully activated MMP-2. In addition, (GPO)10 induced HSC
      migration similar to the platelet-derived growth factor subunit-B. Further, the
      MMP-2-dependent invasion of HT1080 fibrosarcoma cells through an ECM membrane was
      enhanced after addition of (GPO)10. Since cellular proliferation and migration
      concomitant with matrix degradation is stimulated, we conclude that the MMP
      (GPO)10 interaction also functions in a physiological environment. Thus, a
      potential therapeutic effect of (GPO)10 should be further tested in animal models
      for MMP-associated diseases such as colitis or fibrosis. 

PMID- 24688763
TI  - The influence of virus infections on the course of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is extensively influenced by viral
      infections. The mechanisms of how viral agents affect the pathogenesis and
      prognosis of COPD are numerous. In general, patients with infectious
      exacerbations are characterized by longer hospitalization periods and greater
      impairment of several lung function parameters than those with non-infectious
      exacerbations. Prodromal, clinical, and outcome parameters fail to distinguish
      virally from non-virally induced illnesses in cases of exacerbations. The
      importance of infections with respiratory and non-respiratory viral agents for
      pathogenesis and course of COPD is detailed. Human adenovirus, non-respiratory
      viruses including human immunodeficiency virus, human metapneumovirus, influenza
      virus, human rhinovirus, and respiratory syncytial virus are especially stressed.

PMID- 24688765
TI  - The synthetic hydroxyproline-containing collagen analogue (Gly-Pro-Hyp)10
      ameliorates acute DSS colitis.
AB  - In experimental models of and humans with intestinal inflammation, increased
      levels of the matrix-degrading gelatinases MMP-2 and -9 in inflamed tissues can
      be detected. The synthetic collagen analogue (Gly-Pro-Hyp)10, (GPO)10, has been
      identified as a relevant binding structure for proMMP-2/-9 and promotes enzymatic
      activity of proMMP-2. Since targeted MMP strategies might offer promising anti
      inflammatory treatment options, we for the first time studied in vivo actions
      exerted by (GPO)10 applying an acute dextrane sulfate sodium (DSS) induced
      colitis model. Seven-day intraperitoneal (GPO)10 treatment ameliorated clinical
      symptoms and histopathological colonic changes as compared to placebo controls
      with severe colitis. (GPO)10-treated mice displayed a diminished influx of
      neutrophils, and T- and B-lymphocytes into their colonic mucosa whereas numbers
      of regulatory T-cells and regenerative cells were higher as compared to placebo
      controls. Furthermore, IL-6 secretion was down-regulated in ex vivo colonic
      biopsies derived from (GPO)10-treated mice whereas higher concentrations of the
      anti-inflammatory cytokine IL-10 in extra-intestinal compartments such as MLN and
      spleen could be detected. Strikingly, influx of inflammatory cells into lungs was
      abolished following (GPO)10 application. We therefore propose (GPO)10 as a
      promising effective and safe treatment option of intestinal and extra-intestinal
      inflammatory conditions in humans. 

PMID- 24688766
TI  - Malaria burden in human population of Quetta, Pakistan.
AB  - Malaria is a serious global health challenge, which is responsible for more than
      one million deaths a year. Malarial infection is more prevalent in developing
      countries including Pakistan. Significant efforts have been made to control
      malaria; however, due to socio-environmental factors, it remains a frequent
      problem in Quetta. The present study was undertaken to determine the malarial
      incidence, species prevalence, and its demographic evaluation in human population
      of Quetta, Pakistan. A total of 1831 subjects, comprising 1072 male and 759
      female presenting symptoms of malaria, were included in this study. Blood samples
      from clinically suspected individuals were subjected to the standard
      immunochromatographic and malaria parasite smear analysis for malaria diagnosis.
      Out of 1831 subjects, 338 (18.45%) patients were positive for malarial parasite
      while the species prevalence was found as 276 (81.66%) and 62 (18.34%) for
      Plasmodium vivax, and Plasmodium falciparum, respectively. Furthermore, seasonal
      variations gradual increase in the prevalence rate. The age group of 21-30 years
      (30.47%) was found more prone to malaria. The suspected malaria cases were found
      more frequent in rural (72.1%) as compared to urban (27.9%). In addition, the
      malaria burden was high in urban area (22.89%) population as compared to the
      rural area (16.74%) population. It was observed that the highest disease
      occurrence was caused by P. vivax, which reflects a serious threat for public
      health. The current findings will be helpful to plan effective strategies to
      prevent and control malaria in this area. 

PMID- 24688767
TI  - Comparative study of nasal bacterial carriage in pediatric patients from two
      different geographical regions.
AB  - The aim of this study was to determine the prevalence of bacterial carriage in
      the anterior nares of two different patient cohorts, aged 5-15 years. By use of a
      sensitive enrichment broth, Gram-positive and -negative bacteria were cultured
      from the two cohorts of each 100 patients at the Referral Clinic in Eritrea and
      at a German University Hospital. In the German cohort, 27% of the patients were
      positive either for Gram-negative (n=5) or -positive bacteria, including
      Staphylococcus aureus (n=8; MRSA (n=2)), Staphylococcus epidermidis (n=12),
      Corynebacterium spp. (n=4), and Streptococcus pyogenes (n=1). In comparison, the
      Eritrean cohort revealed 33% bacterial carriers in the anterior nares. Among the
      identified species were S. aureus (n=2), S. epidermidis (n=13), Streptococcus
      haemolyticus (n=9), and Gram-negative rods including Klebsiella
      pneumoniae/oxytoca (n=5), Enterobacter agglomerans (n=4), Escherichia coli (n=2),
      and Pseudomonas aeruginosa (n=1). Noteworthy, none of the Eritrean patients were
      positive for MRSA. In both cohorts there was no co-occurrence of Gram-positive
      and -negative bacteria in the anterior nares. However, we observed in two
      subjects of the Eritrean cohort co-colonization with S. epidermidis and S.
      haemolyticus. The occurrence of Gram-negative bacteria was less significant by
      age in the German cohort, whereas in the Eritrean cohort Gram-negative bacteria
      were more frequently detected in carriers aged 5-9 years. Continued surveillance
      of S. aureus and Gram-negative bacteria carriage deserves further attention and
      might help to determine future trends in the characteristics of nasal carriage,
      subsequent incidence of infections, and the potential effectiveness of targeted
      population based intervention. 

PMID- 24688768
TI  - Campylobacter jejuni induces extra-intestinal immune responses via Toll-like
      receptor-4 signaling in conventional IL-10 deficient mice with chronic colitis.
AB  - Campylobacter jejuni is one of the predominant causes for foodborne bacterial
      infections worldwide. We investigated whether signaling of C. jejuni-lipoproteins
      and -lipooligosaccharide via Toll-like-receptor (TLR) -2 and -4, respectively, is
      inducing intestinal and extra-intestinal immune responses following infection of
      conventional IL-10(-/-) mice with chronic colitis. At day 3 following oral
      infection, IL-10(-/-) mice lacking TLR-2 or TLR-4 harbored comparable C. jejuni
      strain ATCC 43431 loads in their colon. Interestingly, infected TLR-4(-/-) IL-10(
      /-) mice displayed less compromized epithelial barrier function as indicated by
      lower translocation rates of live gut commensals into mesenteric lymphnodes
      (MLNs), and exhibited less distinct B lymphocyte responses in their colonic
      mucosa as compared to naive IL-10(-/-) controls. Furthermore, in extra-intestinal
      compartments such as MLNs and spleens, abundance of myeloid cells was less
      distinct whereas relative percentages of activated T helper cells and cytotoxic T
      cells were higher in spleens and dendritic cells more abundant in MLNs of
      infected IL-10(-/-) animals lacking TLR-4 as compared to IL-10(-/-) controls.
      Taken together, in conventionally colonized IL-10(-/-) mice, TLR-4, but not TLR
      2, is involved in mediating extra-intestinal pro-inflammatory immune responses
      following C. jejuni infection. Thus, conventional IL-10(-/-) mice are well suited
      to further dissect mechanisms underlying Campylobacter infections in vivo. 

PMID- 24688769
TI  - Association of complement C3 and interleukin-1 with foot infections in diabetic
      patients.
AB  - The study of the bacteriological profile, the association of complement C3,
      interleukin-1beta, and zinc therapy of diabetic foot ulcers (type two) was
      investigated. Twenty diabetics without foot ulcers (group I), 50 diabetics with
      foot ulcers (group II), and 10 matched normal controls (group III) were enrolled
      in this study. Diabetic foot ulcers were mostly of grade 2. The most frequent
      organisms were Clostridium spp., Staphylococcus aureus, Pseudomonas aeruginosa
      and Escherichia coli, respectively. Vancomycin, Imipenem, and Meropenem were the
      most effective against Gram-positive and Gram-negative aerobes, while Imipenem,
      Meropenem and Chloramphenicol for Gram-positive anaerobes. Group II had abnormal
      levels of C3 (72%). A significant higher concentration of C3 was found in group
      II. Group II had abnormal levels of IL-1beta (60%). A significant higher
      concentration of IL-1beta was found in group II. Zinc therapy (25 mg/day/oral)
      induced a highly significant decrease in the frequency of Gram-positive anaerobes
      and levels of IL-1beta. Significantly increases all mineral concentrations in
      serum level except Mn(+2). The study highlights the prevalence of antibiotic
      multi-drug resistant bacteria causing foot infections in diabetics which require
      combined antimicrobial therapy. Altered levels of serum complement C3 and IL
      1beta might be responsible for depressed immune response which might be causes
      for delayed wound healing and repeated infections. Zinc supplementation may help
      in healing the wounds by enhancing the immune response. 

PMID- 24688770
TI  - IgA antibody production by intrarectal immunization of mice using recombinant
      major capsid protein of hamster polyomavirus.
AB  - Viral proteins are highly antigenic and known as potent stimulators of adaptive
      immune responses. This mechanism is often used for biotechnological applications
      in monoclonal antibody production resulting in high-affinity IgG antibodies in
      most cases. The aim of this study was to increase antigen-specific IgA antibody
      levels in mice in order to generate monoclonal IgA antibodies by hybridoma
      technology. For this purpose, hamster polyomavirus (HaPyV) major capsid protein
      VP1 was used to immunize mice by different routes in order to induce VP1-specific
      IgA titers. Recombinant HaPyV-VP1 was generated in Escherichia coli and
      administered intraperitoneally, orally, and intrarectally. VP1-specific
      antibodies were determined by ELISA in sera and organ culture supernatants. We
      found a significant increase of HaPyV-VP1-specific IgAs in spleen organ cultures
      after rectal immunization of mice but not in cultures of mesenteric lymph nodes,
      colon, or Peyer's patches. In contrast, oral and intraperitoneal immunization did
      not provide an appropriate specific IgA induction at all. These results show that
      specific IgA antibodies can be induced by intrarectal immunization in the spleen.
      The generation of monoclonal IgA antibodies with well-defined properties is a
      useful tool for the investigation of mucosal immune responses or autoimmune
      diseases and extends the spectrum of antibodies with specific effector functions.

PMID- 24688771
TI  - Murine adult neural progenitor cells alter their proliferative behavior and gene
      expression after the activation of Toll-like-receptor 3.
AB  - Viral infections during pregnancy significantly increase the risk for
      psychological pathologies like schizophrenia in the offspring. One of the main
      morphological hallmarks of schizophrenia is a reduced size of the hippocampus.
      Since new neurons are produced in this particular brain compartment throughout
      life, it might be possible that low neurogenesis levels triggered by a maternal
      viral infection contribute to developmental deficits of the hippocampus. We
      injected polyinosinic:polycytidylic acid (Poly I:C) in pregnant C57Bl/6 mice to
      stimulate an anti-viral response through TLR3 and examined gene expressions in
      the neuronal progenitor cells (NPCs) of the offspring at different ages.
      Additionally, we treated adult NPC lines with Poly I:C to investigate its direct
      effect. We could show for the first time that TLR3 and its downstream effector
      molecule IRF3 are expressed in adult NPCs. Poly I:C treatment in vitro and in
      vivo led to the regulation of proliferation and genes involved in antiviral
      response, migration, and survival. These findings indicate that NPCs of the fetus
      are able to react towards an in utero immune response, and thus, changes in the
      neuronal stem cell pool can contribute to the development of neurological
      diseases like schizophrenia. 

PMID- 24688772
TI  - Treatment with interleukin-18 binding protein ameliorates Toxoplasma gondii
      induced small intestinal pathology that is induced by bone marrow cell-derived
      interleukin-18.
AB  - Peroral infection with Toxoplasma gondii results in a Th1-type immunopathology
      characterized by small intestinal necrosis and is dependent on IL-18. In the
      present study, we investigated whether treatment with IL-18 binding protein (IL
      18bp) prevents ileal pathology. We observed increased expression of IL-18bp in
      intestinal biopsies of mice following infection. Whereas small intestines of
      control mice showed severe necrosis with complete destruction of the small
      intestinal architecture, mice treated with IL-18bp daily displayed only mild
      inflammatory changes including flattening of villi and edema in the space between
      the epithelium and lamina propria. Small intestinal parasite loads and
      concentrations of pro-inflammatory cytokines did not differ in control and IL
      18bp-treated mice. Binding of IL-18 to immobilized IL-18bp revealed a remarkably
      slow dissociation rate, indicating high affinity. Using chimeric mice we observed
      that bone marrow-derived rather than stromal cells were the primary source of IL
      18 that resulted in small intestinal pathology following peroral infection with
      T. gondii. In conclusion, the results presented here suggest that IL-18bp may be
      an effective and safe treatment for small intestinal inflammation. Antigen
      presenting rather than epithelial cells appear to be the main source of IL-18 in
      T. gondii-induced small intestinal inflammation. 

PMID- 24688773
TI  - Individualized hypo/hyperfractionated radiotherapy for non-small cell lung
      cancer.

PMID- 24688774
TI  - Exploiting sensitization windows of opportunity in hyper and hypo-fractionated
      radiation therapy.
AB  - In contrast to the conventional radiotherapy/chemoradiotherapy paradigms used in
      the treatment of majority of cancer types, this review will describe two areas of
      radiobiology, hyperfractionated and hypofractionated radiation therapy, for
      cancer treatment focusing on application of novel concepts underlying these
      treatment modalities. The initial part of the review discusses the phenomenon of
      hyper-radiation sensitivity (HRS) at lower doses (0.1 to 0.6 Gy), describing the
      underlying mechanisms and how this could enhance the effects of chemotherapy,
      particularly, in hyperfractionated settings. The second part examines the
      radiobiological/physiological mechanisms underlying the effects of high-dose
      hypofractionated radiation therapy that can be exploited for tumor cure. These
      include abscopal/bystander effects, activation of immune system, endothelial cell
      death and effect of hypoxia with re-oxygenation. These biological properties
      along with targeted dose delivery and distribution to reduce normal tissue
      toxicity may make high-dose hypofractionation more effective than conventional
      radiation therapy for treatment of advanced cancers. The novel radiation physics
      based methods that take into consideration the tumor volume to be irradiated and
      normal tissue avoidance/tolerance can further improve treatment outcome and post
      treatment quality of life. In conclusion, there is enough evidence to further
      explore novel avenues to exploit biological mechanisms from hyper-fractionation
      by enhancing the efficacy of chemotherapy and hypo-fractionated radiation therapy
      that could enhance tumor control and use imaging and technological advances to
      reduce toxicity. 

PMID- 24688775
TI  - Improving radiotherapy planning, delivery accuracy, and normal tissue sparing
      using cutting edge technologies.
AB  - In the United States, more than half of all new invasive cancers diagnosed are
      non-small cell lung cancer, with a significant number of these cases presenting
      at locally advanced stages, resulting in about one-third of all cancer deaths.
      While the advent of stereotactic ablative radiation therapy (SABR, also known as
      stereotactic body radiotherapy, or SBRT) for early-staged patients has improved
      local tumor control to >90%, survival results for locally advanced stage lung
      cancer remain grim. Significant challenges exist in lung cancer radiation therapy
      including tumor motion, accurate dose calculation in low density media, limiting
      dose to nearby organs at risk, and changing anatomy over the treatment course.
      However, many recent technological advancements have been introduced that can
      meet these challenges, including four-dimensional computed tomography (4DCT) and
      volumetric cone-beam computed tomography (CBCT) to enable more accurate target
      definition and precise tumor localization during radiation, respectively. In
      addition, advances in dose calculation algorithms have allowed for more accurate
      dosimetry in heterogeneous media, and intensity modulated and arc delivery
      techniques can help spare organs at risk. New delivery approaches, such as tumor
      tracking and gating, offer additional potential for further reducing target
      margins. Image-guided adaptive radiation therapy (IGART) introduces the potential
      for individualized plan adaptation based on imaging feedback, including bulky
      residual disease, tumor progression, and physiological changes that occur during
      the treatment course. This review provides an overview of the current state of
      the art technology for lung cancer volume definition, treatment planning,
      localization, and treatment plan adaptation. 

PMID- 24688776
TI  - Imaging techniques for tumour delineation and heterogeneity quantification of
      lung cancer: overview of current possibilities.
AB  - Imaging techniques for the characterization and delineation of primary lung
      tumours and lymph nodes are a prerequisite for adequate radiotherapy. Numerous
      imaging modalities have been proposed for this purpose, but only computed
      tomography (CT) and FDG-PET have been implemented in clinical routine. Hypoxia
      PET, dynamic contrast-enhanced CT (DCE-CT), dual energy CT (DECT) and
      (functional) magnetic resonance imaging (MRI) hold promise for the future.
      Besides information on the primary tumour, these techniques can be used for
      quantification of tissue heterogeneity and response. In the future, treatment
      strategies may be designed which are based on imaging techniques to optimize
      individual treatment. 

PMID- 24688777
TI  - Hyperfractionated and accelerated radiotherapy in non-small cell lung cancer.
AB  - Radical radiotherapy plays a major role in the treatment of non-small cell lung
      cancer (NSCLC) due to the fact that many patients are medically or surgically
      inoperable. Advances in technology and radiotherapy delivery allow targeted
      treatment of the disease, whilst minimizing the dose to organs at risk. This in
      turn creates an opportunity for dose escalation and the prospect of tailoring
      radiotherapy treatment to each patient. This is especially important in patients
      deemed unsuitable for chemotherapy or surgery, where there is a need to increase
      the therapeutic gain from radical radiotherapy alone. Recent research into
      fractionation schedules, with hyperfractionated and accelerated radiotherapy
      regimes has been promising. How to combine these new fractionated schedules with
      dose escalation and chemotherapy remains open to debate and there is local,
      national and international variation in management with a lack of overall
      consensus. An overview of the current literature on hyperfractionated and
      accelerated radiotherapy in NSCLC is provided. 

PMID- 24688779
TI  - Accelerated dose escalation with proton beam therapy for non-small cell lung
      cancer.
AB  - Local tumor control remains challenging in many cases of non-small cell lung
      cancer (NSCLC), particularly those that involve large or centrally located
      tumors. Concurrent chemotherapy and radiation can maximize tumor control and
      survival for patients with locally advanced disease, but a substantial proportion
      of such patients cannot tolerate this therapy, and sequential chemoradiation
      regimens or radiation given alone at conventionally fractionated doses produces
      suboptimal results. An alternative approach is the use of hypofractionated proton
      beam therapy (PBT). The energy distribution of protons can be exploited to reduce
      involuntary irradiation of normal tissues, particularly the low-dose irradiation
      problematic in intensity-modulated (photon) radiation therapy (IMRT). Here we
      summarize current evidence on the use of hypofractionated PBT for both early
      stage and locally advanced NSCLC, and the possibility of using hypofractionated
      regimens for patients who are not candidates for concurrent chemotherapy. 

PMID- 24688778
TI  - Radiation dose effect in locally advanced non-small cell lung cancer.
AB  - Radiation is the foundation of treatment for locally advanced non-small cell lung
      cancer (NSCLC), and as such, optimal radiation dose is essential for successful
      treatment. This article will briefly review biological considerations of
      radiation dose and their effect in the context of three-dimensional conformal
      radiation therapy (3D-CRT) including intensity modulated radiation therapy (IMRT)
      and stereotactic body radiation therapy (SBRT) for NSCLC. It will focus on
      literature review and discussions regarding radiation dose effect in locally
      advanced NSCLC including potential severe and lethal toxicities of high dose
      radiation given with concurrent chemotherapy. Potential new approaches for
      delivering safe and effective doses by individualizing treatment based on
      functional imaging are being applied in studies such as the PET boost trial and
      RTOG1106. The RTOG concept of delivering high dose radiation to the more
      resistant tumors with the use of isotoxic dose prescription and adaptive planning
      will also be discussed in detail. 

PMID- 24688781
TI  - Local control rates with five-fraction stereotactic body radiotherapy for
      oligometastatic cancer to the lung.
AB  - OBJECTIVE: To report our institutional experience with five fractions of daily 8
      12 Gy stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic
      cancer to the lung. METHODS: Thirty-four consecutive patients with
      oligometastatic cancers to the lung were treated with image-guided SBRT between
      2008 and 2011. Patient age ranged from 38 to 81 years. There were 17 males and 17
      females. Lung metastases were from the following primary cancer types: colon
      cancer (n=13 patients), head and neck cancer (n=6), breast cancer (n=4), melanoma
      (n=4), sarcoma (n=4) and renal cell carcinoma (n=3). The median prescription dose
      was 50 Gy in five fractions (range, 40-60 Gy) to the isocenter, with the 80%
      isodose line encompassing the planning target volume (PTV) [defined as gross
      tumor volume (GTV) + 7-11 mm volumetric expansion]. The follow-up interval ranged
      from 2.4-54 months, with a median of 16.7 months. RESULTS: The 1-, 2-, and 3-year
      patient local control (LC) rates for all patients were 93%, 88%, and 80%
      respectively. The 1-, 2-, and 3-year overall survival (OS) rates were 62%, 44%,
      and 23% respectively. The 1- and 2-year patient LC rates were 95% and 88% for
      tumor size 1-2 cm (n=25), and 86% for tumor size 2-3 cm (n=7). The majority (n=4)
      of local failures occurred within 12 months. No patient experienced local failure
      after 12 months except for one patient with colon cancer whose tumors progressed
      locally at 26 months. All five patients with local recurrences had colorectal
      cancer. Statistical analyses showed that age, gender, previous chemotherapy,
      previous surgery or radiation had no significant effect on LC rates. No patient
      was reported to have any symptomatic pneumonitis at any time point. CONCLUSIONS:
      SBRT for oligometastatic disease to the lung using 8-12 Gy daily fractions over
      five treatments resulted in excellent 1- and 2-year LC rates. Most local failures
      occurred within the first 12 months, with five local failures associated with
      colorectal cancer. The treatment is safe using this radiation fractionation
      schedule with no therapy-related pneumonitis.

PMID- 24688780
TI  - Combining targeted agents and hypo- and hyper-fractionated radiotherapy in NSCLC.
AB  - Radical radiotherapy remains the cornerstone of treatment for patients with
      unresectable locally advanced non small cell lung cancer (NSCLC) either as single
      modality treatment for poor performance status patients or with sequential or
      concomitant chemotherapy for good performance status patients. Advances in
      understanding of tumour molecular biology, targeted drug development and
      experiences of novel agents in the advanced disease setting have brought targeted
      agents into the NSCLC clinic. In parallel experience using modified accelerated
      fractionation schedules in locally advanced disease have demonstrated improved
      outcomes compared to conventional fractionation in the single modality and
      sequential chemo-radiotherapy settings. Early studies of targeted agents combined
      with (chemo-) radiotherapy in locally advanced disease in different clinical
      settings are discussed below and important areas for future studies are high
      lighted. 

PMID- 24688782
TI  - New techniques for assessing response after hypofractionated radiotherapy for
      lung cancer.
AB  - Hypofractionated radiotherapy (HFRT) is an effective and increasingly-used
      treatment for early stage non-small cell lung cancer (NSCLC). Stereotactic
      ablative radiotherapy (SABR) is a form of HFRT and delivers biologically
      effective doses (BEDs) in excess of 100 Gy10 in 3-8 fractions. Excellent long
      term outcomes have been reported; however, response assessment following SABR is
      complicated as radiation induced lung injury can appear similar to a recurring
      tumor on CT. Current approaches to scoring treatment responses include Response
      Evaluation Criteria in Solid Tumors (RECIST) and positron emission tomography
      (PET), both of which appear to have a limited role in detecting recurrences
      following SABR. Novel approaches to assess response are required, but new
      techniques should be easily standardized across centers, cost effective, with
      sensitivity and specificity that improves on current CT and PET approaches. This
      review examines potential novel approaches, focusing on the emerging field of
      quantitative image feature analysis, to distinguish recurrence from fibrosis
      after SABR. 

PMID- 24688784
TI  - Stories of Special K patients.

PMID- 24688783
TI  - Molecular markers to predict clinical outcome and radiation induced toxicity in
      lung cancer.
AB  - The elucidation of driver mutations involved in the molecular pathogenesis of
      cancer has led to a surge in the application of novel targeted therapeutics in
      lung cancer. Novel oncologic research continues to lead investigators towards
      targeting personalized tumor characteristics rather than applying targeted
      therapy to broad patient populations. Several driver genes, in particular
      epidermal growth factor receptor (EGFR) and ALK fusions, are the earliest to have
      made their way into clinical trials. The avant-garde role of genomic profiling
      has led to important clinical challenges when adapting current standard
      treatments to personalized oncologic care. This new frontier of medicine requires
      newer biomarkers for toxicity that will identify patients at risk, as well as,
      new molecular markers to predict and assess clinical outcomes. Thus far, several
      signature genes have been developed to predict outcome as well as genetic factors
      related to inflammation to predict toxicity. 

PMID- 24688785
TI  - Donor-recipient size mismatch in paediatric renal transplantation.
AB  - Introduction. End stage renal failure in children is a rare but devastating
      condition, and kidney transplantation remains the only permanent treatment
      option. The aim of this review was to elucidate the broad surgical issues
      surrounding the mismatch in size of adult kidney donors to their paediatric
      recipients. Methods. A comprehensive literature search was undertaken on PubMed,
      MEDLINE, and Google Scholar for all relevant scientific articles published to
      date in English language. Manual search of the bibliographies was also performed
      to supplement the original search. Results. Size-matching kidneys for
      transplantation into children is not feasible due to limited organ availability
      from paediatric donors, resulting in prolonged waiting list times. Transplanting
      a comparatively large adult kidney into a child may lead to potential challenges
      related to the surgical incision and approach, vessel anastomoses, wound closure,
      postoperative cardiovascular stability, and age-correlated maturation of the
      graft. Conclusion. The transplantation of an adult kidney into a size mismatched
      paediatric recipient significantly reduces waiting times for surgery; however, it
      presents further challenges in terms of both the surgical procedure and the post
      operative management of the patient's physiological parameters. 

PMID- 24688786
TI  - Larvicidal Activity of Cassia occidentalis (Linn.) against the Larvae of
      Bancroftian Filariasis Vector Mosquito Culex quinquefasciatus.
AB  - Background & Objectives. The plan of this work was to study the larvicidal
      activity of Cassia occidentalis (Linn.) against the larvae of Culex
      quinquefasciatus. These larvae are the most significant vectors. They transmit
      the parasites and pathogens which cause a deadly disease like filariasis, dengue,
      yellow fever, malaria, Japanese encephalitis, chikungunya, and so forth, which
      are considered harmful towards the population in tropic and subtropical regions.
      Methods. The preliminary laboratory trail was undertaken to determine the
      efficacy of petroleum ether and N-butanol extract of dried whole plant of Cassia
      occidentalis (Linn.) belonging to the family Caesalpiniaceae at various
      concentrations against the late third instar larvae of Culex quinquefasciatus by
      following the WHO guidelines. Results. The results suggest that 100% mortality
      effect of petroleum ether and N-butanol extract of Cassia occidentalis (Linn.)
      was observed at 200 and 300 ppm (parts per million). The results obviously showed
      use of plants in insect control as an alternative method for minimizing the
      noxious effect of some pesticide compounds on the environment. Thus the extract
      of Cassia occidentalis (Linn.) is claimed as more selective and biodegradable
      agent. Conclusion. This study justified that plant Cassia occidentalis (Linn.)
      has a realistic mortality result for larvae of filarial vector. This is safe to
      individual and communities against mosquitoes. It is a natural weapon for
      mosquito control. 

PMID- 24688787
TI  - Larvicidal Activity against Aedes aegypti and Molluscicidal Activity against
      Biomphalaria glabrata of Brazilian Marine Algae.
AB  - This study investigated the biological activities of five benthic marine algae
      collected from Northeastern Region of Brazil. The tested activities included
      larvicidal activity against Aedes aegypti, molluscicidal activity against
      Biomphalaria glabrata, and toxicity against Artemia salina. Extracts of Ulva
      lactuca (Chlorophyta), Padina gymnospora, Sargassum vulgare (Phaeophyta), Hypnea
      musciformis, and Digenea simplex (Rhodophyta) were prepared using different
      solvents of increasing polarity, including dichloromethane, methanol, ethanol,
      and water. Of the extracts screened, the dichloromethane extracts of H.
      musciformis and P. gymnospora exhibited the highest activities and were subjected
      to bioassay-guided fractionation in hexane and chloroform. The chloroform
      fractions of the P. gymnospora and H. musciformis extracts showed molluscicidal
      activity at values below 40  MU g.mL(-1) (11.1460  MU g.mL(-1) and 25.8689  MU
      g.mL(-1), resp.), and the chloroform and hexane fractions of P. gymnospora showed
      larvicidal activity at values below 40  MU g.mL(-1) (29.018  MU g.mL(-1) and
      17.230  MU g.mL(-1), resp.). The crude extracts were not toxic to A. salina,
      whereas the chloroform and hexane fractions of P. gymnospora (788.277  MU g.mL(
      1) and 706.990  MU g.mL(-1)) showed moderate toxicity, indicating that the toxic
      compounds present in these algae are nonpolar. 

PMID- 24688788
TI  - Association of eNOS polymorphisms with anterior chamber depth in han chinese:
      jiangsu eye study.
AB  - Recently, a study reported that single nucleotide polymorphisms (SNP) in
      endothelial nitric oxide synthase (eNOS) were associated with primary angle
      closure glaucoma (PACG) in Australian cohort. In this study, we aimed to
      investigate whether those eNOS SNPs are associated with primary angle closure
      (PAC) or ocular biometric characteristics such as axial length (AL), anterior
      chamber depth (ACD), and diopter of spherical power (DS) in Han Chinese. The
      samples consisted of 232 PAC subjects and 306 controls collected from a
      population-based prevalence survey conducted in Funing County of Jiangsu, China.
      The rs3793342 and rs11771443 in eNOS were genotyped by TaqMan-MGB probe using the
      RT-PCR system. Our data did not identify any association of the eNOS SNPs with
      PAC. However, the analysis on the quantitative traits of ocular biometrics showed
      that the ACD of rs11771443 AA and GA carriers is significantly deeper than that
      of rs11771443 GG carriers (P = 0.0025), even though the AL and DS are not
      associated with rs11771443 genotypes. Rs3793342 was not associated with any
      biometric parameters including ACD, AL and DS. In summary, our data indicates
      that eNOS rs11771443 is associated with ACD and its role in the pathogenesis of
      PACG warranted further study. 

PMID- 24688789
TI  - Management of hypertension in intrapericardial paraganglioma.
AB  - Functioning paraganglioma is extra-adrenal catecholamine-secreting tumours that
      may cause secondary hypertension. Primary intrapericardial paragangliomas are
      very rare and are located adjacent to the great vessels or heart, typically near
      the left atrium. These tumours are an exceptionally uncommon finding during the
      investigation of refractory hypertension. However, in recent years,
      intrapericardial paragangliomas have been diagnosed incidentally with increased
      frequency, due to the extensive use of radiologic chest imaging. The mainstay of
      treatment of functioning intrapericardial paraganglioma is surgical removal,
      which usually achieves blood pressure normalization. Due to the locations of
      these tumours, the surgical approach is through a median sternotomy or
      posterolateral thoracotomy, and manipulation-induced catecholamine release may
      cause paroxysmal hypertension. Typically in these patients, blood pressure
      fluctuates dramatically intra- and post-operatively, increasing the risk of
      cardiovascular complications. We review here the current modalities of
      perioperative fluid and hypotensive drug administration in the setting of surgery
      for functioning intrapericardial paraganglioma and discuss the recently proposed
      paradigm shift that omits preoperative preparation. 

PMID- 24688790
TI  - A Potential Link between Environmental Triggers and Autoimmunity.
AB  - Autoimmune diseases have registered an alarming rise worldwide in recent years.
      Accumulated evidence indicates that the immune system's ability to distinguish
      self from nonself is negatively impacted by genetic factors and environmental
      triggers. Genetics is certainly a factor, but since it normally takes a very long
      time for the human genetic pattern to change enough to register on a worldwide
      scale, increasingly the attention of studies has been focused on the
      environmental factors of a rapidly changing and evolving civilization. New
      technology, new industries, new inventions, new chemicals and drugs, and new
      foods and diets are constantly and rapidly being introduced in this fast-paced
      ever-changing world. Toxicants, infections, epitope spreading, dysfunctions of
      immune homeostasis, and dietary components can all have an impact on the body's
      delicate immune recognition system. Although the precise etiology and
      pathogenesis of many autoimmune diseases are still unknown, it would appear from
      the collated studies that there are common mechanisms in the immunopathogenesis
      of multiple autoimmune reactivities. Of particular interest is the citrullination
      of host proteins and their conversion to autoantigens by the aforementioned
      environmental triggers. The identification of these specific triggers of
      autoimmune reactivity is essential then for the development of new therapies for
      autoimmune diseases. 

PMID- 24688791
TI  - Outcomes and utilization of a low intensity workplace weight loss program.
AB  - Obesity is related to high health care costs and lost productivity in the
      workplace. Employers are increasingly sponsoring weight loss and wellness
      programs to ameliorate these costs. We evaluated weight loss outcomes, treatment
      utilization, and health behavior change in a low intensity phone- and web-based,
      employer-sponsored weight loss program. The intervention included three proactive
      counseling phone calls with a registered dietician and a behavioral health coach
      as well as a comprehensive website. At six months, one third of those who
      responded to the follow-up survey had lost a clinically significant amount of
      weight (>=5% of body weight). Clinically significant weight loss was predicted by
      the use of both the counseling calls and the website. When examining specific
      features of the web site, the weight tracking tool was the most predictive of
      weight loss. Health behavior changes such as eating more fruits and vegetables,
      increasing physical activity, and reducing stress were all predictive of
      clinically significant weight loss. Although limited by the low follow-up rate,
      this evaluation suggests that even low intensity weight loss programs can lead to
      clinical weight loss for a significant number of participants. 

PMID- 24688792
TI  - Adherence to Long-Term Therapies and Beliefs about Medications.
AB  - Objectives. To assess adherence to long-term medications among patients in family
      medicine clinics and to evaluate relationship between adherence, beliefs about
      medications, medication information adequacy, and other factors. Methods.
      Interviewer assisted survey was conducted to assess adherence using the 8-item
      Morisky Medication Adherence Scale (MMAS-8), beliefs about medications using
      beliefs about medicine questionnaire (BMQ), and the patients' perception of
      medication information adequacy. Results. Of the 408 participants, 56.9% reported
      low adherence. Pearson's bivariate correlation showed positive association
      between MMAS-8 score and BMQ-specific necessity (r = 0.526  P < 0.001) and the
      perceived information adequacy (r = 0.568  P < 0.001), and there was negative
      association between adherence score and BMQ specific concerns, general overuse,
      and harm (r = -0.647, -0.466, and -0.663, resp.) (P < 0.001). Multivariable
      analysis revealed that age, number of medications, number of medical conditions,
      specific necessity and concerns beliefs, general harm beliefs, and perceived
      adequacy of medication information were independent predictor of adherence.
      Furthermore, specific beliefs explain 27.7% of the variance in adherence, while
      medication information adequacy explains 32.3% of the variance in adherence.
      Conclusion. The prevalence of low adherence among patients on long-term
      medications is high and it is related to negative beliefs about medications and
      to inadequate information given to patients about their medications. 

PMID- 24688793
TI  - Mucormycosis in a renal transplant recipient: case report and comprehensive
      review of literature.
AB  - Mucormycosis is a rare but devastating infection. We present a case of fatal
      disseminated mucormycosis infection in a renal transplant patient. Uncontrolled
      diabetes mellitus and immunosuppression are the major predisposing factors to
      infection with Mucorales. Mucorales are angioinvasive and can infect any organ
      system. Lungs are the predominant site of infection in solid organ transplant
      recipients. Prompt diagnosis is challenging and influences outcome. Treatment
      involves a combination of surgical and medical therapies. Amphotericin B remains
      the cornerstone in the medical management of mucormycosis, although other agents
      have been used. Newer agents are promising. 

PMID- 24688794
TI  - Emergency Ultrasound Predicting the Need for Therapeutic Laparotomy among Blunt
      Abdominal Trauma Patients in a Sub-Saharan African Hospital.
AB  - Background. The trauma burden globally accounts for high levels of mortality and
      morbidity. Blunt abdominal trauma (BAT) contributes significantly to this burden.
      Patient's evaluation for BAT remains a diagnostic challenge for emergency
      physicians. SSORTT gives a score that can predict the need for laparotomy. The
      objective of this study was to assess the accuracy of SSORTT score in predicting
      the need for a therapeutic laparotomy after BAT. Method. A prospective
      observational study. Eligible patients were evaluated for shock and the presence
      of haemoperitoneum using a portable ultrasound machine. Further evaluation of
      patients following the standard of care (SOC) protocol was done. The accuracy of
      SSORTT score in predicting therapeutic laparotomy was compared to SOC. Results.
      In total, 195 patients were evaluated; M : F ratio was 6 : 1. The commonest
      injuries were to the head 80 (42%) and the abdomen 54 (28%). A SSORTT score of >2
      appropriately identified patients that needed a therapeutic laparotomy (with
      sensitivity 90%, specificity 90%, PPV 53%, and NPV 98%). The overall mortality
      rate was 17%. Conclusion. Patients with a SSORTT score of 2 and above had a high
      likelihood of requiring a therapeutic laparotomy. SSORTT scoring should be
      adopted for routine practice in low technology settings. 

PMID- 24688795
TI  - Impact of undetected comorbidity on treatment and outcomes of breast cancer.
AB  - Preexisting comorbidity adversely impacts breast cancer treatment and outcomes.
      We examined the incremental impact of comorbidity undetected until cancer. We
      followed breast cancer patients in SEER-Medicare from 12 months before to 84
      months after diagnosis. Two comorbidity indices were constructed: the National
      Cancer Institute index, using 12 months of claims before cancer, and a second
      index for previously undetected conditions, using three months after cancer.
      Conditions present in the first were excluded from the second. Overall, 6,184
      (10.1%) had >=1 undetected comorbidity. Chronic obstructive pulmonary disease
      (38%) was the most common undetected condition. In multivariable analyses that
      adjusted for comorbidity detected before cancer, older age, later stage, higher
      grade, and poor performance status all were associated with higher odds of >=1
      undetected comorbidity. In stage I-III cancer, undetected comorbidity was
      associated with lower adjusted odds of receiving adjuvant chemotherapy (Odds
      Ratio (OR) = 0.81, 95% Confidence Interval (CI) 0.73-0.90, P < 0.0001; OR = 0.38,
      95% CI 0.30-0.49, P < 0.0001; index score 1 or >=2, respectively), and with
      increased mortality (Hazard Ratio (HR) = 1.45, 95% CI 1.38-1.53, P < 0.0001; HR =
      2.38, 95% CI 2.18-2.60, P < 0.0001; index score 1 or >=2). Undetected comorbidity
      is associated with less aggressive treatment and higher mortality in breast
      cancer. 

PMID- 24688796
TI  - Evolution of the B-Block Binding Subunit of TFIIIC That Binds to the Internal
      Promoter for RNA Polymerase III.
AB  - Eukaryotic RNA polymerase III transcribes tRNA genes, and this requires the
      transcription factor TFIIIC. Promoters are within genes, with which the B-block
      binding subunit of TFIIIC associates to initiate transcription. The binding
      subunits are more than 1000 amino acids in length in various eukaryotic species.
      There are four regions with conserved sequence similarities in the subunits. The
      helix-turn-helix motif is included in one of these regions and has been
      characterized as the B-block_TFIIIC family in the Pfam database. In the NCBI and
      EMBL translated protein databases, there are archaeal proteins (approximately 100
      amino acids in length) referred to as B-block binding subunits. Most of them
      contain a B-block_TFIIIC motif. DELTA-BLAST searches using these archaeal
      proteins as queries showed significant multiple blast hits for many eukaryotic B
      block binding subunits on the same proteins. This result suggests that eukaryotic
      B-block binding subunits were constituted by repeating a small unit of B
      block_TFIIIC over a long evolutionary period. Bacterial proteins have also been
      annotated as B-block binding subunits in the databases. Here, some of them were
      confirmed to have significant similarities to B-block_TFIIIC. These results may
      imply that part of the RNAP III transcription machinery existed in the common
      ancestry of prokaryotes and eukaryotes. 

PMID- 24688797
TI  - Solid phase microextraction and related techniques for drugs in biological
      samples.
AB  - In drug discovery and development, the quantification of drugs in biological
      samples is an important task for the determination of the physiological
      performance of the investigated drugs. After sampling, the next step in the
      analytical process is sample preparation. Because of the low concentration levels
      of drug in plasma and the variety of the metabolites, the selected extraction
      technique should be virtually exhaustive. Recent developments of sample handling
      techniques are directed, from one side, toward automatization and online coupling
      of sample preparation units. The primary objective of this review is to present
      the recent developments in microextraction sample preparation methods for
      analysis of drugs in biological fluids. Microextraction techniques allow for less
      consumption of solvent, reagents, and packing materials, and small sample volumes
      can be used. In this review the use of solid phase microextraction (SPME),
      microextraction in packed sorbent (MEPS), and stir-bar sorbtive extraction (SBSE)
      in drug analysis will be discussed. In addition, the use of new sorbents such as
      monoliths and molecularly imprinted polymers will be presented. 

PMID- 24688799
TI  - Health communication cards as a tool for behaviour change.
AB  - Individuals seeking healthcare treatment in the context of obesity often
      experience difficulty engaging in discussions around their health and face
      challenges finding consensus with practitioners on care plans that best suit
      their lives. The complex set of biological, social, and environmental variables
      that have contributed to the higher prevalence of obesity are well illustrated in
      the foresight obesity system map. Effectively understanding and addressing key
      variables for each individual has proven to be difficult, with clinicians facing
      barriers and limited resources to help address patients' unique needs. However,
      productive discussions inspired by patient centered care may be particularly
      effective in promoting behaviour change. Tools based on systems science that
      facilitate patient centered care and help identify behaviour change priorities
      have not been developed to help treat adult obesity. This project created and
      pilot tested a card based clinical communication tool designed to help facilitate
      conversations with individuals engaged in health behaviour change. The health
      communication cards were designed to help direct conversation between patients
      and healthcare providers toward issues relevant to the individual. Use of the
      cards to facilitate patient driven conversations in clinical care may help to
      streamline conversations, set realistic care plan goals, and improve long term
      rates of compliance. 

PMID- 24688798
TI  - Mechanism of human tooth eruption: review article including a new theory for
      future studies on the eruption process.
AB  - Human eruption is a unique developmental process in the organism. The aetiology
      or the mechanism behind eruption has never been fully understood and the
      scientific literature in the field is extremely sparse. Human and animal tissues
      provide different possibilities for eruption analyses, briefly discussed in the
      introduction. Human studies, mainly clinical and radiological, have focused on
      normal eruption and gender differences. Why a tooth begins eruption and what
      enables it to move eruptively and later to end these eruptive movements is not
      known. Pathological eruption courses contribute to insight into the aetiology
      behind eruption. A new theory on the eruption mechanism is presented.
      Accordingly, the mechanism of eruption depends on the correlation between space
      in the eruption course, created by the crown follicle, eruption pressure
      triggered by innervation in the apical root membrane, and the ability of the
      periodontal ligament to adapt to eruptive movements. Animal studies and studies
      on normal and pathological eruption in humans can support and explain different
      aspects in the new theory. The eruption mechanism still needs elucidation and the
      paper recommends that future research on eruption keeps this new theory in mind.
      Understanding the aetiology of the eruption process is necessary for treating
      deviant eruption courses. 

PMID- 24688800
TI  - Carbon nanofiber multiplexed array and Wireless Instantaneous Neurotransmitter
      Concentration Sensor for simultaneous detection of dissolved oxygen and dopamine.
AB  - PURPOSE: While the mechanism of Deep Brain Stimulation (DBS) remains poorly
      understood, previous studies have shown that it evokes release of neurochemicals
      and induces activation of functional magnetic resonance imaging (fMRI) blood
      oxygen level-dependent signal in distinct areas of the brain. Therefore, the main
      purpose of this paper is to demonstrate the capabilities of the Wireless
      Instantaneous Neurotransmitter Concentration Sensor system (WINCS) in conjunction
      with a carbon nanofiber (CNF) multiplexed array electrode as a powerful tool for
      elucidating the mechanism of DBS through the simultaneous detection of multiple
      bioactive-molecules. METHODS: Patterned CNF nanoelectrode arrays were prepared on
      a 4-inch silicon wafer where each device consists of 3 * 3 electrode pads, 200
      MUm square, that contain CNFs spaced at 1MUm intervals. The multiplexed carbon
      nanofiber CNF electrodes were integrated with WINCS to detect mixtures of
      dopamine (DA) and oxygen (O2) using fast scan cyclic voltammetry (FSCV) in vitro.
      RESULTS: First, simultaneous detection of O2 at two spatially different
      locations, 200 um apart, was demonstrated. Second, simultaneous detection of both
      O2 and DA at two spatially different locations, using two different decoupled
      waveforms was demonstrated. Third, controlled studies demonstrated that the
      waveform must be interleaved to avoid electrode crosstalk artifacts in the
      acquired data. CONCLUSIONS: Multiplexed CNF nanoelectrode arrays for
      electrochemical detection of neurotransmitters show promise for the detection of
      multiple analytes with the application of time independent decoupled waveforms.
      Electrochemistry on CNF electrodes may be helpful in elucidating the mechanism of
      DBS, and may also provide the precision and sensitivity required for future
      applications in feedback modulated DBS neural control systems.

PMID- 24688801
TI  - Dopamine measurement during prolonged deep brain stimulation: a proof-of
      principle study of paired pulse voltammetry.
AB  - PURPOSE: Deep Brain Stimulation (DBS) has been effective in treating various
      neurological and psychiatric disorders; however, its underlying mechanism hasn't
      been completely understood. Fast scan cyclic voltammetry (FSCV) is a valuable
      tool to elucidate underlying neurotransmitter mechanisms of DBS, due to its sub
      second temporal resolution and direct identification of analytes. However, since
      DBS-like high frequency stimulation evokes neurotransmitter release as well as
      extracellular pH shift, it is hard to isolate the neurotransmitter signal from
      the complex environment. Here we demonstrate the efficacy of a modified FSCV
      technique, Paired Pulse Voltammetry (PPV), in detecting dopamine (DA) release in
      the caudate nucleus during long-term electrical stimulation of the medial
      forebrain bundle (MFB) in the rat. METHODS: Unlike traditional FSCV applying a
      single triangular waveform, PPV employs a binary waveform with a specific time
      gap (2.2 ms) in between the comprising pulses. DA measurement was performed with
      a carbon fiber microelectrode placed in the caudate nucleus and a twisted bipolar
      stimulating electrode in the MFB. PPV data was collected with the Wireless
      Instantaneous Neurochemical Concentration Sensing System (WINCS). RESULTS: Using
      PPV, the detection of DA was evident throughout the long-term stimulation (5
      minutes); however, without PPV, in vivo environmental changes including pH shift
      eventually obscured the characteristic oxidation current of DA at 0.6V.
      CONCLUSIONS: These results indicate that PPV can be a valuable tool to accurately
      determine DA dynamics in a complex in vivo environment during long-term
      electrical stimulation.

PMID- 24688802
TI  - A Genre-Specific Investigation of Video Game Engagement and Problem Play in the
      Early Life Course.
AB  - This study explored predictors of engagement with specific video game genres, and
      degree of problem play experienced by players of specific genres, during the
      early life course. Video game players ages 18-29 (n = 692) were recruited in and
      around video game retail outlets, arcades, conventions, and other video game
      related contexts in New York City. Participants completed a Computer-Assisted
      Personal Interview (CAPI) of contemporaneous demographic and personality measures
      and a Life-History Calendar (LHC) measuring video gaming, school/work engagement,
      and caffeine and sugar consumption for each year of life ages 6 - present.
      Findings were that likelihood of engagement with most genres rose during
      childhood, peaked at some point during the second decade of life, and declined
      through emerging adulthood. Cohorts effects on engagement also emerged which were
      probably attributable to changes in the availability and popularity of various
      genres over the 12-year age range of our participants. The relationship between
      age and problem play of most genres was either negative or non-significant.
      Sensation-seeking was the only consistent positive predictor of problem play.
      Relationships between other variables and engagement with and problem play of
      specific genres are discussed in detail.

PMID- 24688803
TI  - In vivo micro-vascular imaging and flow cytometry in zebrafish using two-photon
      excited endogenous fluorescence.
AB  - Zebrafish has rapidly evolved as a powerful vertebrate model organism for
      studying human diseases. Here we first demonstrate a new label-free approach for
      in vivo imaging of microvasculature, based on the recent discovery and detailed
      characterization of the two-photon excited endogenous fluorescence in the blood
      plasma of zebrafish. In particular, three-dimensional reconstruction of the
      microvascular networks was achieved with the depth-resolved two-photon excitation
      fluorescence (TPEF) imaging. Secondly, the blood flow images, obtained by
      perpendicularly scanning the focal point across the blood vessel, provided
      accurate information for characterizing the hemodynamics of the circulatory
      system. The endogenous fluorescent signals of reduced nicotinamide adenine
      dinucleotide (NADH) enabled visualization of the circulating granulocytes
      (neutrophils) in the blood vessel. The development of acute sterile inflammation
      could be detected by the quantitative counting of circulating neutrophils.
      Finally, we found that by utilizing a short wavelength excitation at 650 nm, the
      commonly used fluorescent proteins, such as GFP and DsRed, could be efficiently
      excited together with the endogenous fluorophores to achieve four-color TPEF
      imaging of the vascular structures and blood cells. The results demonstrated that
      the multi-color imaging could potentially yield multiple view angles of important
      processes in living biological systems. 

PMID- 24688804
TI  - Retinal cell imaging in myopic chickens using adaptive optics multiphoton
      microscopy.
AB  - Abnormal eye growth induced by visual deprivation can modify the structure and
      density of the retinal cells. We have used an adaptive optics multiphoton
      microscope to image photoreceptors (PRs) and ganglion cells (GCs) at different
      retinal locations in unstained retinas of chicken eyes with about 10D of myopia
      and their normal-sighted fellow eyes. In all samples, the local averaged inter-PR
      distance increased with eccentricity. No significant differences in PR density
      were found between control and myopic eyes. GC density declined in myopic eyes
      compared to control eyes and the inter-cell distance increased. In normal eyes,
      the size of the GC cell bodies increased approximately two-fold between the area
      centralis and the peripheral retina. In myopic eyes, this trend was preserved but
      the GC bodies were larger at each retinal location, compared to control eyes.
      Obviously, GC morphology is changing when the retinal area is enlarged in myopic
      eyes. 

PMID- 24688805
TI  - Diffuse reflectance spectroscopy of epithelial tissue with a smart fiber-optic
      probe.
AB  - Diffuse reflectance spectroscopy (DRS) with a fiber-optic probe can noninvasively
      quantify the optical properties of epithelial tissues and has shown the potential
      as a cost-effective, fast and sensitive tool for diagnosis of early precancerous
      changes in the cervix and oral cavity. However, current DRS systems are
      susceptible to several sources of systematic and random errors, such as
      uncontrolled probe-to-tissue pressure and lack of a real-time calibration that
      can significantly impair the measurement accuracy, reliability and validity of
      this technology as well as its clinical utility. In addition, such systems use
      bulky, high power and expensive optical components which impede their widespread
      use in low- and middle-income countries (LMICs) where epithelial cancer related
      death is disproportionately high. In this paper we report a portable, easy-to-use
      and low cost, yet accurate and reliable DRS device that can aid in the screening
      and diagnosis of oral and cervical cancer. The device uses an innovative smart
      fiber-optic probe to eliminate operator bias, state-of-the-art photonics
      components to reduce size and power consumption, and automated software to reduce
      the need of operator training. The device showed a mean error of 1.4 +/- 0.5% and
      6.8 +/- 1.7% for extraction of phantom absorption and reduced scattering
      coefficients, respectively. A clinical study on healthy volunteers indicated that
      a pressure below 1.0 psi is desired for oral mucosal tissues to minimize the
      probe effects on tissue physiology and morphology. 

PMID- 24688806
TI  - 4D tracking of clinical seminal samples for quantitative characterization of
      motility parameters.
AB  - In this paper we investigate the use of a digital holographic microscope, with
      partial spatial coherent illumination, for the automated detection and tracking
      of spermatozoa. This in vitro technique for the analysis of quantitative
      parameters is useful for assessment of semen quality. In fact, thanks to the
      capabilities of digital holography, the developed algorithm allows us to resolve
      in-focus amplitude and phase maps of the cells under study, independently of
      focal plane of the sample image. We have characterized cell motility on clinical
      samples of seminal fluid. In particular, anomalous sperm cells were characterized
      and the quantitative motility parameters were compared to those of normal sperm. 

PMID- 24688807
TI  - Law of cooling, heat conduction and Stefan-Boltzmann radiation laws fitted to
      experimental data for bones irradiated by CO2 laser.
AB  - The rate of cooling of domesticated pig bones is investigated within the
      temperature range of 20 degrees C-320 degrees C. Within the afore-mentioned
      temperature range, it was found that different behaviors in the rate of cooling
      were taking place. For bones reaching a temperature within the lower temperature
      range of 20 degrees C-50 degrees C, it was found that the rate of cooling is
      mostly governed by the empirical Newton's law of cooling. It is also shown that a
      transition is taking place somewhere within 50 degrees C-100 degrees C, where
      both the heat conduction equation and Newton's law apply. As bones can be raised
      at a fairly high temperature before burning, it was found that the rate of
      cooling within the range 125 degrees C-320 degrees C is mostly behaving according
      to the heat conduction equation and Stefan-Boltzmann radiation law. A pulsed CO2
      laser was used to heat the bones up to a given temperature and the change of
      temperature as a function of time was recorded by non-contact infrared
      thermometer during the cooling period. 

PMID- 24688808
TI  - Microstructure of subretinal drusenoid deposits revealed by adaptive optics
      imaging.
AB  - Subretinal drusenoid deposits (SDD), a recently recognized lesion associated with
      progression of age-related macular degeneration, were imaged with adaptive optics
      scanning laser ophthalmoscopy (AO-SLO) and optical coherence tomography (AO-OCT).
      AO-SLO revealed a distinct en face structure of stage 3 SDD, showing a
      hyporeflective annulus surrounded reflective core packed with hyperreflective
      dots bearing a superficial similarity to the photoreceptors in the unaffected
      retina. However, AO-OCT suggested that the speckled appearance over the SDD
      rendered by AO-SLO was the lesion material itself, rather than photoreceptors. AO
      OCT assists proper interpretation and understanding of the SDD structure and the
      lesions' impact on surrounding photoreceptors produced by AO-SLO and vice versa. 

PMID- 24688809
TI  - Opposed-view dark-field digital holographic microscopy.
AB  - Scattering and absorption belong to the major problems in imaging the internal
      layers of a biological specimen. Due to the structural inhomogeneity of the
      specimen, the distribution of the structures in the upper layers of a given
      internal structure of interest is different from the lower layers that may result
      in different interception of scattered light, falling into the angular aperture
      of the microscope objective, from the object in each imaging view. Therefore,
      different spatial frequencies of the scattered light can be acquired from
      different (top and bottom) views. We have arranged an opposed-view dark-field
      digital holographic microscope (DHM) to collect the scattered light concurrently
      from both views with the aim to increase the contrast of internal structures and
      improve the signal-to-noise ratio. Implementing a DHM system gives the
      possibility to implement digital refocusing process and obtain multilayer images
      from each side without a depth scan of the object. The method is explained and
      the results are presented exemplary for a Drosophila embryo. 

PMID- 24688810
TI  - Microdroplet temperature calibration via thermal dissociation of quenched DNA
      oligomers.
AB  - The development of microscale analytical techniques has created an increasing
      demand for reliable and accurate heating at the microscale. Here, we present a
      novel method for calibrating the temperature of microdroplets using quenched,
      fluorescently labeled DNA oligomers. Upon melting, the 3' fluorophore of the
      reporter oligomer separates from the 5' quencher of its reverse complement,
      creating a fluorescent signal recorded as a melting curve. The melting
      temperature for a given oligomer is determined with a conventional quantitative
      polymerase chain reaction (qPCR) instrument and used to calibrate the temperature
      within a microdroplet, with identical buffer concentrations, heated with an
      infrared laser. Since significant premelt fluorescence prevents the use of a
      conventional (single-term) sigmoid or logistic function to describe the melting
      curve, we present a three-term sigmoid model that provides a very good match to
      the asymmetric fluorescence melting curve with premelting. Using mixtures of
      three oligomers of different lengths, we fit multiple three-term sigmoids to
      obtain precise comparison of the microscale and macroscale fluorescence melting
      curves using "extrapolated two-state" melting temperatures. 

PMID- 24688811
TI  - Conical scan polarization-sensitive optical coherence tomography.
AB  - We report on a new articular cartilage imaging technique with potential for
      clinical arthroscopic use, by supplementing the variable-incidence-angle
      polarization-sensitive optical coherence tomography method previously developed
      by us with a conical beam scan protocol. The technique is validated on bovine
      tendon by comparing experimental data with simulated data generated using the
      extended Jones matrix calculus. A unique capability of this new optical technique
      is that it can locate the "brushing direction" of collagen fibers in articular
      cartilage, which is structural information that extends beyond established
      methods such as split-line photography or birefringent fast-axis measurement in
      that it is uniquely defined over the full azimuthal-angle range of (-pi, + pi).
      The mapping of this direction over the cartilage surface may offer insights into
      the optimal design of tissue-engineering scaffolds for cartilage repair. 

PMID- 24688812
TI  - Hadamard multiplexed fluorescence tomography.
AB  - Depth-resolved three-dimensional (3D) reconstruction of fluorophore-tagged
      inclusions in fluorescence tomography (FT) poses a highly ill-conditioned problem
      as depth information must be extracted from boundary data. Due to the ill-posed
      nature of the FT inverse problem, noise and errors in the data can severely
      impair the accuracy of the 3D reconstructions. The signal-to-noise ratio (SNR) of
      the FT data strongly affects the quality of the reconstructions. Additionally, in
      FT scenarios where the fluorescent signal is weak, data acquisition requires
      lengthy integration times that result in excessive FT scan periods. Enhancing the
      SNR of FT data contributes to the robustness of the 3D reconstructions as well as
      the speed of FT scans. A major deciding factor in the SNR of the FT data is the
      power of the radiation illuminating the subject to excite the administered
      fluorescent reagents. In existing single-point illumination FT systems, the
      source power level is limited by the skin maximum radiation exposure levels. In
      this paper, we introduce and study the performance of a multiplexed fluorescence
      tomography system with orders-of-magnitude enhanced data SNR over existing
      systems. The proposed system allows for multi-point illumination of the subject
      without jeopardizing the information content of the FT measurements and results
      in highly robust reconstructions of fluorescent inclusions from noisy FT data.
      Improvements offered by the proposed system are validated by numerical and
      experimental studies. 

PMID- 24688813
TI  - TestSTORM: Simulator for optimizing sample labeling and image acquisition in
      localization based super-resolution microscopy.
AB  - Localization-based super-resolution microscopy image quality depends on several
      factors such as dye choice and labeling strategy, microscope quality and user
      defined parameters such as frame rate and number as well as the image processing
      algorithm. Experimental optimization of these parameters can be time-consuming
      and expensive so we present TestSTORM, a simulator that can be used to optimize
      these steps. TestSTORM users can select from among four different structures with
      specific patterns, dye and acquisition parameters. Example results are shown and
      the results of the vesicle pattern are compared with experimental data. Moreover,
      image stacks can be generated for further evaluation using localization
      algorithms, offering a tool for further software developments. 

PMID- 24688814
TI  - Quantitative upper airway endoscopy with swept-source anatomical optical
      coherence tomography.
AB  - Minimally invasive imaging of upper airway obstructions in children and adults is
      needed to improve clinical decision-making. Toward this goal, we demonstrate an
      anatomical optical coherence tomography (aOCT) system delivered via a small-bore,
      flexible endoscope to quantify the upper airway lumen geometry. Helical scans
      were obtained from a proximally-scanned fiber-optic catheter of 820 MUm outer
      diameter and >2 mm focal length. Coupled with a long coherence length wavelength
      swept light source, the system exhibited an SNR roll-off of < 10 dB over a 10 mm
      range. Operating at 10 rotations/s, the average accuracy of segmented cross
      sectional areas was found to be -1.4 +/- 1.0%. To demonstrate the capability of
      this system, aOCT was performed on a pediatric airway phantom and on ex vivo
      swine trachea. The ability for quantitative endoscopy afforded by this system can
      aid in diagnosis, medical and surgical decision making, and predictive modeling
      of upper airway obstructive disorders. 

PMID- 24688815
TI  - Neurotoxic effects of indocyanine green -cerebellar granule cell culture
      viability study.
AB  - The aim of this study was to examine neurotoxicity indocyanine green (ICG). We
      assessed viability of primary cerebellar granule cell culture (CGC) exposed to
      ICG to test two mechanisms that could be the first triggers causing neuronal
      toxicity: imbalance in calcium homeostasis and the degree of oligomerization of
      ICG molecules. We have observed this imbalance in CGC after exposure to 75
      125MUMU ICG and dose and application sequence dependent protective effect of
      Gadovist on surviving neurons in vitro when used with ICG. Spectroscopic studies
      suggest the major cause of toxicity of the ICG is connected with oligomers
      formation. ICG at concentration of 25 MUM (which is about 4 times higher than the
      highest concentration of ICG in the brain applied in in-vivo human studies) is
      not neurotoxic in the cell culture. 

PMID- 24688816
TI  - Assessing blood coagulation status with laser speckle rheology.
AB  - We have developed and investigated a novel optical approach, Laser Speckle
      Rheology (LSR), to evaluate a patient's coagulation status by measuring the
      viscoelastic properties of blood during coagulation. In LSR, a blood sample is
      illuminated with laser light and temporal speckle intensity fluctuations are
      measured using a high-speed CMOS camera. During blood coagulation, changes in the
      viscoelastic properties of the clot restrict Brownian displacements of light
      scattering centers within the sample, altering the rate of speckle intensity
      fluctuations. As a result, blood coagulation status can be measured by relating
      the time scale of speckle intensity fluctuations with clinically relevant
      coagulation metrics including clotting time and fibrinogen content. Our results
      report a close correlation between coagulation metrics measured using LSR and
      conventional coagulation results of activated partial thromboplastin time,
      prothrombin time and functional fibrinogen levels, creating the unique
      opportunity to evaluate a patient's coagulation status in real-time at the point
      of care. 

PMID- 24688817
TI  - Optical-thermal light-tissue interactions during photoacoustic breast imaging.
AB  - Light-tissue interactions during photoacoustic imaging, including dynamic heat
      transfer processes in and around vascular structures, are not well established. A
      three-dimensional, transient, optical-thermal computational model was used to
      simulate energy deposition, temperature distributions and thermal damage in
      breast tissue during exposure to pulsed laser trains at 800 and 1064 nm. Rapid
      and repetitive temperature increases and thermal relaxation led to
      superpositioning effects that were highly dependent on vessel diameter and depth.
      For a ten second exposure at established safety limits, the maximum single-pulse
      and total temperature rise levels were 0.2 degrees C and 5.8 degrees C,
      respectively. No significant thermal damage was predicted. The impact of tissue
      optical properties, surface boundary condition and irradiation wavelength on peak
      temperature location and temperature evolution with time are discussed. 

PMID- 24688818
TI  - Detection of swelling of single isolated mitochondrion with optical microscopy.
AB  - Volume regulation under osmotic loading is one of the most fundamental functions
      in cells and organelles. However, the effective method to detect volume changes
      of a single organelle has not been developed. Here, we present a novel technique
      for detecting volume changes of a single isolated mitochondrion in aqueous
      solution based on the transmittance of the light through the mitochondrion. We
      found that 70% and 21% of mitochondria swelled upon addition of a hypotonic
      solution and Ca(2+), respectively. These results show the potential of the
      present technique to detect the physiological volume changes of individual small
      organelles such as mitochondria. 

PMID- 24688820
TI  - Optical multichannel room temperature magnetic field imaging system for clinical
      application.
AB  - Optically pumped magnetometers (OPM) are a very promising alternative to the
      superconducting quantum interference devices (SQUIDs) used nowadays for Magnetic
      Field Imaging (MFI), a new method of diagnosis based on the measurement of the
      magnetic field of the human heart. We present a first measurement combining a
      multichannel OPM-sensor with an existing MFI-system resulting in a fully
      functional room temperature MFI-system. 

PMID- 24688819
TI  - Myofibrillar misalignment correlated to triad disappearance of mdx mouse
      gastrocnemius muscle probed by SHG microscopy.
AB  - We show that the canonical single frequency sarcomeric SHG intensity pattern (SHG
      IP) of control muscles is converted to double frequency sarcomeric SHG-IP in
      preserved mdx mouse gastrocnemius muscles in the vicinity of necrotic fibers.
      These double frequency sarcomeric SHG-IPs are often spatially correlated to
      double frequency sarcomeric two-photon excitation fluorescence (TPEF) emitted
      from Z-line and I-bands and to one centered spot SHG angular intensity pattern
      (SHG-AIP) suggesting that these patterns are signature of myofibrillar
      misalignement. This latter is confirmed with transmission electron microscopy
      (TEM). Moreover, a good spatial correlation between SHG signature of myofibrillar
      misalignment and triad reduction is established. Theoretical simulation of
      sarcomeric SHG-IP is used to demonstrate the correlation between change of SHG-IP
      and -AIP and myofibrillar misalignment. The extreme sensitivity of SHG microscopy
      to reveal the submicrometric organization of A-band thick filaments is
      highlighted. This report is a first step toward future studies aimed at
      establishing live SHG signature of myofibrillar misalignment involving excitation
      contraction defects due to muscle damage and disease. 

PMID- 24688821
TI  - 2-D PSTD Simulation of the time-reversed ultrasound-encoded deep-tissue imaging
      technique.
AB  - We present a robust simulation technique to model the time-reversed
      ultrasonically encoded (TRUE) technique for deep-tissue imaging. The
      pseudospectral time-domain (PSTD) algorithm is employed to rigorously model the
      electromagnetic wave interaction of light propagating through a macroscopic
      scattering medium. Based upon numerical solutions of Maxwell's equations, the
      amplitude and phase are accurately accounted for to analyze factors that affect
      the TRUE propagation of light through scattering media. More generally, we
      demonstrate the feasibility of modeling light propagation through a virtual
      tissue model of macroscopic dimensions with numerical solutions of Maxwell's
      equations. 

PMID- 24688822
TI  - Optical coherence tomography detection of shear wave propagation in inhomogeneous
      tissue equivalent phantoms and ex-vivo carotid artery samples.
AB  - In this work, we explored the potential of measuring shear wave propagation using
      optical coherence elastography (OCE) in an inhomogeneous phantom and carotid
      artery samples based on a swept-source optical coherence tomography (OCT) system.
      Shear waves were generated using a piezoelectric transducer transmitting sine
      wave bursts of 400 MUs duration, applying acoustic radiation force (ARF) to
      inhomogeneous phantoms and carotid artery samples, synchronized with a swept
      source OCT (SS-OCT) imaging system. The phantoms were composed of gelatin and
      titanium dioxide whereas the carotid artery samples were embedded in gel.
      Differential OCT phase maps, measured with and without the ARF, detected the
      microscopic displacement generated by shear wave propagation in these phantoms
      and samples of different stiffness. We present the technique for calculating
      tissue mechanical properties by propagating shear waves in inhomogeneous tissue
      equivalent phantoms and carotid artery samples using the ARF of an ultrasound
      transducer, and measuring the shear wave speed and its associated properties in
      the different layers with OCT phase maps. This method lays the foundation for
      future in-vitro and in-vivo studies of mechanical property measurements of
      biological tissues such as vascular tissues, where normal and pathological
      structures may exhibit significant contrast in the shear modulus. 

PMID- 24688823
TI  - Isotropic scalar image visualization of vector differential image data using the
      inverse Riesz transform.
AB  - X-ray Talbot moire interferometers can now simultaneously generate two
      differential phase images of a specimen. The conventional approach to integrating
      differential phase is unstable and often leads to images with loss of visible
      detail. We propose a new reconstruction method based on the inverse Riesz
      transform. The Riesz approach is stable and the final image retains visibility of
      high resolution detail without directional bias. The outline Riesz theory is
      developed and an experimentally acquired X-ray differential phase data set is
      presented for qualitative visual appraisal. The inverse Riesz phase image is
      compared with two alternatives: the integrated (quantitative) phase and the
      modulus of the gradient of the phase. The inverse Riesz transform has the
      computational advantages of a unitary linear operator, and is implemented
      directly as a complex multiplication in the Fourier domain also known as the
      spiral phase transform. 

PMID- 24688824
TI  - Handheld multispectral fluorescence lifetime imaging system for in vivo
      applications.
AB  - There is an increasing interest in the application of fluorescence lifetime
      imaging (FLIM) for medical diagnosis. Central to the clinical translation of FLIM
      technology is the development of compact and high-speed clinically compatible
      systems. We present a handheld probe design consisting of a small maneuverable
      box fitted with a rigid endoscope, capable of continuous lifetime imaging at
      multiple emission bands simultaneously. The system was characterized using
      standard fluorescent dyes. The performance was then further demonstrated by
      imaging a hamster cheek pouch in vivo, and oral mucosa tissue both ex vivo and in
      vivo, all using safe and permissible exposure levels. Such a design can greatly
      facilitate the evaluation of FLIM for oral cancer imaging in vivo. 

PMID- 24688825
TI  - Development of a high power supercontinuum source in the 1.7 MUm wavelength
      region for highly penetrative ultrahigh-resolution optical coherence tomography.
AB  - We developed a high power supercontinuum source at a center wavelength of 1.7 MUm
      to demonstrate highly penetrative ultrahigh-resolution optical coherence
      tomography (UHR-OCT). A single-wall carbon nanotube dispersed in polyimide film
      was used as a transparent saturable absorber in the cavity configuration and a
      high-repetition-rate ultrashort-pulse fiber laser was realized. The developed SC
      source had an output power of 60 mW, a bandwidth of 242 nm full-width at half
      maximum, and a repetition rate of 110 MHz. The average power and repetition rate
      were approximately twice as large as those of our previous SC source [20]. Using
      the developed SC source, UHR-OCT imaging was demonstrated. A sensitivity of 105
      dB and an axial resolution of 3.2 MUm in biological tissue were achieved. We
      compared the UHR-OCT images of some biological tissue samples measured with the
      developed SC source, the previous one, and one operating in the 1.3 MUm
      wavelength region. We confirmed that the developed SC source had improved
      sensitivity and penetration depth for low-water-absorption samples. 

PMID- 24688826
TI  - Spatial light modulator based active wide-field illumination for ex vivo and in
      vivo quantitative NIR FRET imaging.
AB  - Fluorescence lifetime imaging is playing an increasing role in drug development
      by providing a sensitive method to monitor drug delivery and receptor-ligand
      interactions. However, the wide dynamic range of fluorescence intensity emitted
      by ex vivo and in vivo samples presents challenges in retrieving information over
      the whole subject accurately and quantitatively. To overcome this challenge, we
      developed an active wide-field illumination (AWFI) strategy based on a spatial
      light modulator that acquires optimal fluorescence signals by enhancing the
      dynamic range, signal to noise ratio, and estimation of lifetime-based
      parameters. We demonstrate the ability of AWFI to estimate Forster resonance
      energy transfer (FRET) donor fraction from dissected organs with high accuracy
      (standard deviation <6%) over the whole field of view, in contrast with the
      homogenous wide-field illumination. We further report its successful application
      to quantitative FRET imaging in a live mouse. AWFI allows improved detection of
      weak signals and enhanced quantitative accuracy in ex vivo and in vivo molecular
      fluorescence quantitative imaging. The technique allows for robust quantitative
      estimation of the bio-distribution of molecular probes and lifetime-based
      parameters over an extended imaging field exhibiting a large range of
      fluorescence intensities and at a high acquisition speed (less than 1 min). 

PMID- 24688827
TI  - In vivo adaptive optics microvascular imaging in diabetic patients without
      clinically severe diabetic retinopathy.
AB  - We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image
      the retina of subjects with non-proliferative diabetic retinopathy (NPDR). To
      improve visualization of different retinal features, the size and alignment of
      the confocal aperture were varied. The inner retinal layers contained clearly
      visualized retinal vessels. In diabetic subjects there was extensive capillary
      remodeling despite the subjects having only mild or moderate NPDR. Details of the
      retinal microvasculature were readily imaged with a larger confocal aperture.
      Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor
      layer images showed regions of bright cones and dark areas, corresponding in
      location to overlying vascular abnormalities and retinal edema. Clinically
      undetected intraretinal vessel remodeling and varying blood flow patterns were
      found. Perifoveal capillary diameters were larger in the diabetic subjects
      (p<0.01), and small arteriolar walls were thickened, based on wall to lumen
      measurements (p<.05). The results suggest that existing clinical classifications
      based on lower magnification clinical assessment may not adequately measure key
      vascular differences among individuals with NPDR. 

PMID- 24688828
TI  - Reliable recovery of the optical properties of multi-layer turbid media by
      iteratively using a layered diffusion model at multiple source-detector
      separations.
AB  - Accurately determining the optical properties of multi-layer turbid media using a
      layered diffusion model is often a difficult task and could be an ill-posed
      problem. In this study, an iterative algorithm was proposed for solving such
      problems. This algorithm employed a layered diffusion model to calculate the
      optical properties of a layered sample at several source-detector separations
      (SDSs). The optical properties determined at various SDSs were mutually
      referenced to complete one round of iteration and the optical properties were
      gradually revised in further iterations until a set of stable optical properties
      was obtained. We evaluated the performance of the proposed method using frequency
      domain Monte Carlo simulations and found that the method could robustly recover
      the layered sample properties with various layer thickness and optical property
      settings. It is expected that this algorithm can work with photon transport
      models in frequency and time domain for various applications, such as
      determination of subcutaneous fat or muscle optical properties and monitoring the
      hemodynamics of muscle. 

PMID- 24688829
TI  - Influence of Comorbidities: Neuropathy, Vasculopathy, and Diabetes on Healing
      Response Quality.
AB  - SIGNIFICANCE: Prolonged and nonhealing connective tissue injuries are often seen
      associated with common diseases, such as metabolic disorders, obesity,
      hypertension, arteriosclerosis, neuropathy, and diabetes mellitus and these
      influences result in considerable burden on society via the health care system,
      the economy, and quality of life for patients. RECENT ADVANCES: Emerging findings
      have established important new links in our understanding of effective connective
      tissue healing. Thereby, the function of the nervous system, vascular supply, and
      metabolic state of the patient can be directly linked to the quality of the
      connective tissue healing process. CRITICAL ISSUES: As some of these conditions
      are also more common in individuals as they age, and aging can also impact
      healing effectiveness, such complications will have an emerging significant
      impact as the demographics of many societies change with expanding percentages of
      the populations >60-65 years of age. FUTURE DIRECTIONS: Comorbidities have to be
      early identified in patients with acute wounds or planned surgery. Necessary
      interactions between physicians with different subspecialties have to be
      initiated to optimize wound healing potentials.

PMID- 24688830
TI  - Proteases and Delayed Wound Healing.
AB  - SIGNIFICANCE: Proteases and their inhibitors contribute to the balance between
      extracellular matrix (ECM) degradation and deposition, creating an equilibrium
      that is essential for the timely and coordinated healing of cutaneous wounds.
      However, when this balance is disrupted, wounds are led into a state of
      chronicity characterized by abundant levels of proteases and decreased levels of
      protease inhibitors. RECENT ADVANCES: Researchers have sought to investigate the
      roles of proteases within both acute and chronic wounds and how the manipulation
      of protease activity may aid healing. Indeed, numerous wound dressings have been
      developed that target such proteases in an attempt to promote wound healing.
      CRITICAL ISSUES: The normal tissue response to injury involves a complex
      interaction between cells and cellular mediators. In particular, the inflammatory
      response is augmented in chronic wounds which are characterized by elevated
      levels of proinflammatory cytokines and proteases. While controlling levels of
      inflammation and protease expression is a critical part of normal wound healing,
      elevated and prolonged expression of proteases produced during the inflammatory
      phase of healing can lead to excessive ECM degradation associated with impaired
      healing. FUTURE DIRECTIONS: It seems plausible that future research should aim to
      investigate the ways in which proteases may be targeted as an alternative
      therapeutic approach to wound management and to assess the benefits and draw
      backs of utilizing wound fluids to assess wound progression in terms of
      proteolytic activity.

PMID- 24688831
TI  - A Study of the Effect of Shiunko, a Traditional Chinese Herbal Medicine, on
      Fibroblasts and Its Implication on Wound Healing Processes.
AB  - SIGNIFICANCE: In China, traditional Chinese medicine (TCM) has been used for
      thousands of years for various acute and chronic wound care. Thus, there is a
      growing need to explore the possible benefits of TCM on wound healing. RECENT
      ADVANCES: Nowadays, in China and some Asian countries including Korea, Japan, and
      Singapore, Chinese herbal therapy is used as an alternative treatment in wound
      care. Therefore, exploration of the possible benefits of TCM on wound healing is
      necessary. CRITICAL ISSUES: Development of TCM is based on the concept of Yin
      (negative phenomenon of nature) and Yang (positive phenomenon of nature). These
      opposing and complementary natural phenomena of the universe restore the normal
      physiological functions, consequently curing diseases and restoring health of a
      patient. FUTURE DIRECTIONS: Due to lack of evidence-based research, TCM
      treatments are not widely accepted in the western world. Using state-of-the-art
      technology such as proteomics, bioinformatics, and biomolecular techniques,
      research studies may lead to more effective remedies for wound care in the
      future.

PMID- 24688832
TI  - Integrative study of Arabidopsis thaliana metabolomic and transcriptomic data
      with the interactive MarVis-Graph software.
AB  - State of the art high-throughput technologies allow comprehensive experimental
      studies of organism metabolism and induce the need for a convenient presentation
      of large heterogeneous datasets. Especially, the combined analysis and
      visualization of data from different high-throughput technologies remains a key
      challenge in bioinformatics. We present here the MarVis-Graph software for
      integrative analysis of metabolic and transcriptomic data. All experimental data
      is investigated in terms of the full metabolic network obtained from a reference
      database. The reactions of the network are scored based on the associated data,
      and sub-networks, according to connected high-scoring reactions, are identified.
      Finally, MarVis-Graph scores the detected sub-networks, evaluates them by means
      of a random permutation test and presents them as a ranked list. Furthermore,
      MarVis-Graph features an interactive network visualization that provides
      researchers with a convenient view on the results. The key advantage of MarVis
      Graph is the analysis of reactions detached from their pathways so that it is
      possible to identify new pathways or to connect known pathways by previously
      unrelated reactions. The MarVis-Graph software is freely available for academic
      use and can be downloaded at: http://marvis.gobics.de/marvis-graph. 

PMID- 24688833
TI  - Comparison of lodgepole and jack pine resin chemistry: implications for range
      expansion by the mountain pine beetle, Dendroctonus ponderosae (Coleoptera:
      Curculionidae).
AB  - The mountain pine beetle, Dendroctonus ponderosae, is a significant pest of
      lodgepole pine in British Columbia (BC), where it has recently reached an
      unprecedented outbreak level. Although it is native to western North America, the
      beetle can now be viewed as a native invasive because for the first time in
      recorded history it has begun to reproduce in native jack pine stands within the
      North American boreal forest. The ability of jack pine trees to defend themselves
      against mass attack and their suitability for brood success will play a major
      role in the success of this insect in a putatively new geographic range and host.
      Lodgepole and jack pine were sampled along a transect extending from the beetle's
      historic range (central BC) to the newly invaded area east of the Rocky Mountains
      in north-central Alberta (AB) in Canada for constitutive phloem resin terpene
      levels. In addition, two populations of lodgepole pine (BC) and one population of
      jack pine (AB) were sampled for levels of induced phloem terpenes. Phloem resin
      terpenes were identified and quantified using gas chromatography. Significant
      differences were found in constitutive levels of terpenes between the two species
      of pine. Constitutive alpha-pinene levels - a precursor in the biosynthesis of
      components of the aggregation and antiaggregation pheromones of mountain pine
      beetle - were significantly higher in jack pine. However, lower constitutive
      levels of compounds known to be toxic to bark beetles, e.g., 3-carene, in jack
      pine suggests that this species could be poorly defended. Differences in wounding
      induced responses for phloem accumulation of five major terpenes were found
      between the two populations of lodgepole pine and between lodgepole and jack
      pine. The mountain pine beetle will face a different constitutive and induced
      phloem resin terpene environment when locating and colonizing jack pine in its
      new geographic range, and this may play a significant role in the ability of the
      insect to persist in this new host. 

PMID- 24688834
TI  - Alkalinity to calcium flux ratios for corals and coral reef communities:
      variances between isolated and community conditions.
AB  - Calcification in reef corals and coral reefs is widely measured using the
      alkalinity depletion method which is based on the fact that two protons are
      produced for every mole of CaCO3 precipitated. This assumption was tested by
      measuring the total alkalinity (TA) flux and Ca(2+) flux of isolated components
      (corals, alga, sediment and plankton) in reference to that of a mixed-community.
      Experiments were conducted in a flume under natural conditions of sunlight,
      nutrients, plankton and organic matter. A realistic hydrodynamic regime was
      provided. Groups of corals were run separately and in conjunction with the other
      reef components in a mixed-community. The TA flux to Ca(2+) flux ratio (DeltaTA:
      DeltaCa(2+)) was consistently higher in the coral-only run (2.06 +/- 0.19) than
      in the mixed-community run (1.60 +/- 0.14, p-value = 0.011). The pH was higher
      and more stable in the mixed-community run (7.94 +/- 0.03 vs. 7.52 +/- 0.07, p
      value = 3 * 10(-5)). Aragonite saturation state (Omega arag) was also higher in
      the mixed-community run (2.51 +/- 0.2 vs. 1.12 +/- 0.14, p-value = 2 * 10(-6)).
      The sediment-only run revealed that sediment is the source of TA that can account
      for the lower DeltaTA: DeltaCa(2+) ratio in the mixed-community run. The
      macroalgae-only run showed that algae were responsible for the increased pH in
      the mixed-community run. Corals growing in a mixed-community will experience an
      environment that is more favorable to calcification (higher daytime pH due to
      algae photosynthesis, additional TA and inorganic carbon from sediments, higher
      Omega arag). A paradox is that the alkalinity depletion method will yield a lower
      net calcification for a mixed-community versus a coral-only community due to TA
      recycling, even though the corals may be calcifying at a higher rate due to a
      more optimal environment. 

PMID- 24688835
TI  - When is an ecological network complex? Connectance drives degree distribution and
      emerging network properties.
AB  - Connectance and degree distributions are important components of the structure of
      ecological networks. In this contribution, we use a statistical argument and
      simple network generating models to show that properties of the degree
      distribution are driven by network connectance. We discuss the consequences of
      this finding for (1) the generation of random networks in null-model analyses,
      and (2) the interpretation of network structure and ecosystem properties in
      relationship with degree distribution. 

PMID- 24688836
TI  - Craniofacial ontogeny in Centrosaurus apertus.
AB  - Centrosaurus apertus, a large bodied ceratopsid from the Late Cretaceous of North
      America, is one of the most common fossils recovered from the Belly River Group.
      This fossil record shows a wide diversity in morphology and size, with specimens
      ranging from putative juveniles to fully-grown individuals. The goal of this
      study was to reconstruct the ontogenetic changes that occur in the craniofacial
      skeleton of C. apertus through a quantitative cladistic analysis. Forty-seven
      cranial specimens were independently coded in separate data matrices for 80
      hypothetical multistate growth characters and 130 hypothetical binary growth
      characters. Both analyses yielded the max-limit of 100,000 most parsimonious
      saved trees and the strict consensus collapsed into large polytomies. In order to
      reduce conflict resulting from missing data, fragmentary individuals were removed
      and the analyses were rerun. Among both the complete and the reduced data sets
      the multistate analyses recovered a shorter tree with a higher consistency index
      (CI) than the additive binary data sets. The arrangement within the trees shows a
      progression of specimens with a recurved nasal horn in the least mature
      individuals, followed by specimens with straight nasal horns in relatively more
      mature individuals, and finally specimens with procurved nasal horns in the most
      mature individuals. The most mature individuals are further characterized by the
      reduction of the cranial horn ornamentations in late growth stages, a trait that
      similarly occurs in the growth of other dinosaurs. Bone textural changes were
      found to be sufficient proxies for relative maturity in individuals that have not
      reached adult size. Additionally, frill length is congruent with relative
      maturity status and makes an acceptable proxy for ontogenetic status, especially
      in smaller individuals. In adult-sized individuals, the fusion of the
      epiparietals and episquamosals and the orientation of the nasal horn are the best
      indicators of relative maturity. This study recovers no clear evidence for
      sexually specific display structures or size dimorphism in C. apertus. 

PMID- 24688837
TI  - Regulation of antimycin biosynthesis by the orphan ECF RNA polymerase sigma
      factor sigma (AntA.).
AB  - Antimycins are an extended family of depsipeptides that are made by filamentous
      actinomycete bacteria and were first isolated more than 60 years ago. Recently,
      antimycins have attracted renewed interest because of their activities against
      the anti-apoptotic machineries inside human cells which could make them promising
      anti-cancer compounds. The biosynthetic pathway for antimycins was recently
      characterised but very little is known about the organisation and regulation of
      the antimycin (ant) gene cluster. Here we report that the ant gene cluster in
      Streptomyces albus is organized into four transcriptional units; the antBA,
      antCDE, antGF and antHIJKLMNO operons. Unusually for secondary metabolite
      clusters, the antG and antH promoters are regulated by an extracytoplasmic
      function (ECF) RNA polymerase sigma factor named sigma (AntA) which represents a
      new sub-family of ECF sigma factors that is only found in antimycin producing
      strains. We show that sigma (AntA) controls production of the unusual precursor 3
      aminosalicylate which is absolutely required for the production of antimycins.
      sigma (AntA) is highly conserved in antimycin producing strains and the -10 and 
      35 elements at the sigma (AntA) regulated antG and antH promoters are also highly
      conserved suggesting a common mechanism of regulation. We also demonstrate that
      altering the C-terminal Ala-Ala residues found in all sigma (AntA) proteins to
      Asp-Asp increases expression of the antFG and antGHIJKLMNO operons and we
      speculate that this Ala-Ala motif may be a signal for the protease ClpXP. 

PMID- 24688838
TI  - Success rate of IR midazolam sedation in combination with C-CLAD in pediatric
      dental patients-a prospective observational study.
AB  - Objective. To evaluate the success rate of intra-rectal (IR) midazolam in
      combination with nitrous oxide/oxygen (N2O) sedation in young uncooperative
      dental patients when the local anesthesia is delivered by a computerized
      controlled local anesthetic delivery (C-CLAD). Study Design. This observational
      study consisted of 219 uncooperative children (age: 4.3 +/- 1.69 y) who received
      IR midazolam (0.4 mg/kg) and N2O to complete their dental treatment. Measured
      variables included: child's pain disruptive behavior during delivery of
      anesthesia by C-CLAD (CHEOP Scale), child behavior during treatment (Houpt
      scale), dental procedure performed, and side effects that appeared during
      treatment. Results. There was a high level of cooperation (mean score: 6.69 +/-
      2.1) during administration of local anesthesia. Good-to-excellent behavior was
      shown by 87% of the children during treatment. Planned treatment was completed by
      184 (92%) patients. No statistically significant changes were noticed in the
      oxygen saturation levels before and after treatment. Children with side effects
      included 3 (1.3%) with nistagmus, 5 (2.3%) with diplopia, and 18 (8.2%) with
      hiccups. Three consecutive sedations decreased the overall behavior score by 5.7%
      compared to the first appointment (p < .05). Conclusions. IR midazolam-N2O
      sedation in combination with C-CLAD is very effective for delivery of dental
      treatment to young uncooperative children. 

PMID- 24688839
TI  - Hawksbill * loggerhead sea turtle hybrids at Bahia, Brazil: where do their
      offspring go?
AB  - Hybridization between hawksbill (Eretmochelys imbricata) and loggerhead (Caretta
      caretta) breeding groups is unusually common in Bahia state, Brazil. Such
      hybridization is possible because hawksbill and loggerhead nesting activities
      overlap temporally and spatially along the coast of this state. Nevertheless, the
      destinations of their offspring are not yet known. This study is the first to
      identify immature hawksbill * loggerhead hybrids (n = 4) from this rookery by
      analyzing the mitochondrial DNA (mtDNA) of 157 immature turtles morphologically
      identified as hawksbills. We also compare for the first time modeled dispersal
      patterns of hawksbill, loggerhead, and hybrid offspring considering hatching
      season and oceanic phase duration of turtles. Particle movements varied according
      to season, with a higher proportion of particles dispersing southwards throughout
      loggerhead and hybrid hatching seasons, and northwards during hawksbill season.
      Hybrids from Bahia were not present in important hawksbill feeding grounds of
      Brazil, being detected only at areas more common for loggerheads. The genetic and
      oceanographic findings of this work indicate that these immature hybrids, which
      are morphologically similar to hawksbills, could be adopting behavioral traits
      typical of loggerheads, such as feeding in temperate waters of the western South
      Atlantic. Understanding the distribution, ecology, and migrations of these
      hybrids is essential for the development of adequate conservation and management
      plans. 

PMID- 24688840
TI  - Existence of benefit finding and posttraumatic growth in people treated for head
      and neck cancer: a systematic review.
AB  - Background. The impact of head and neck cancer (HNC) in long-term survivors
      differs widely among individuals, and a significant number of them suffer from
      the negative effects of disease, whereas others report significant positive
      effect. This systematic review investigated the evidence the implications of
      treatment for HNC and subsequent development of Benefit Finding (BF) or
      Posttraumatic Growth (PTG). Purpose. To understand how differing medical,
      psychological and social characteristics of HNC may lead to BF/PTG and
      subsequently inform post-treatment interventions to encourage positive outcomes.
      Method. In February 2012, five databases including Pubmed, and Psych Info, were
      searched, for peer-reviewed English-language publications. Search strings
      included key words pertaining to HNC, BF, and PTG. One thousand three hundred and
      sixty three publications were identified, reviewed, and reduced following
      Cochrane guidelines and inclusion/exclusion criteria specified by a group of
      maxillofacial consultants and psychologists. Publications were then quality
      assessed using the CASP Cohort Critical Appraisal tool. Findings. Five
      manuscripts met the search and selection criteria, and were sourced for review.
      All studies were identified as being level IIb evidence which is a medium level
      of quality. The majority of studies investigated benefit finding (80%) and were
      split between recruiting participant via cancer clinics and postal survey. They
      focused on the medical, psychological and social characteristics of the patient
      following completion of treatment for HNC. Conclusion. Demographic factors across
      the papers showed similar patterns of relationships across BF and PTG; that
      higher education/qualification and cohabitation/marriage are associated with
      increased BF/PTG. Similarly, overlap with disease characteristics and
      psychosocial factors where hope and optimism were both positively correlated with
      increased reported BF/PTG. 

PMID- 24688841
TI  - Absence of Helicobacter pylori is not protective against peptic ulcer bleeding in
      elderly on offending agents: lessons from an exceptionally low prevalence
      population.
AB  - Aim. Helicobacter pylori (H. pylori) infection is exceptionally rare in
      population from the north-eastern region of Peninsular Malaysia. This provides us
      an opportunity to contemplate the future without H. pylori in acute non-variceal
      upper gastrointestinal (GI) bleeding. Methods. All cases in the GI registry with
      GI bleeding between 2003 and 2006 were reviewed. Cases with confirmed non
      variceal aetiology were analysed. Rockall score > 5 was considered high risk for
      bleeding and primary outcomes studied were in-hospital mortality, recurrent
      bleeding and need for surgery. Results. The incidence of non-variceal upper GI
      bleeding was 2.2/100,000 person-years. Peptic ulcer bleeding was the most common
      aetiology (1.8/100,000 person-years). In-hospital mortality (3.6%), recurrent
      bleeding (9.6%) and need for surgery (4.0%) were uncommon in this population with
      a largely low risk score (85.2% with score <=5). Elderly were at greater risk for
      bleeding (mean 68.5 years, P = 0.01) especially in the presence of duodenal
      ulcers (P = 0.04) despite gastric ulcers being more common. NSAIDs, aspirin and
      co-morbidities were the main risk factors. Conclusions. The absence of H. pylori
      infection may not reduce the risk of peptic ulcer bleeding in the presence of
      risk factors especially offending drugs in the elderly. 

PMID- 24688842
TI  - The rediscovery and redescription of the holotype of the Late Jurassic turtle
      Plesiochelys etalloni.
AB  - Plesiochelyidae are a major component of Late Jurassic shallow marine
      environments throughout Europe. However, the taxonomy of plesiochelyid turtles is
      rather confused. Over the years, many taxa have been synonymized with
      Plesiochelys etalloni, one of the first described species. However, the holotype
      of P. etalloni (and only specimen known from Lect, the type locality) was lost
      for more than 150 years. This specimen has been recently rediscovered in the
      collections of the Musee d'archeologie du Jura in Lons-le-Saunier, France. For
      the first time since its original description in 1857, the holotype of P.
      etalloni is redescribed and compared to relevant material. The taxonomic status
      of this taxon is revised accordingly. Based on the morphology of the newly
      rediscovered holotype and on a reassessment of specimens from Solothurn
      (Switzerland), the species P. solodurensis, P. sanctaeverenae and P. langii are
      synonymized with P. etalloni. Known skull-shell associations for P. etalloni are
      re-evaluated in light of the new morphological information available since the
      rediscovery of this holotype specimen. Finally, we confirm that Plesiochelys is
      represented by a single species in the Late Jurassic of the Jura Mountains. 

PMID- 24688843
TI  - The affective profiles, psychological well-being, and harmony: environmental
      mastery and self-acceptance predict the sense of a harmonious life.
AB  - Background. An important outcome from the debate on whether wellness equals
      happiness, is the need of research focusing on how psychological well-being might
      influence humans' ability to adapt to the changing environment and live in
      harmony. To get a detailed picture of the influence of positive and negative
      affect, the current study employed the affective profiles model in which
      individuals are categorised into groups based on either high positive and low
      negative affect (self-fulfilling); high positive and high negative affect (high
      affective); low positive and low negative affect (low affective); and high
      negative and low positive affect (self-destructive). The aims were to (1)
      investigate differences between affective profiles in psychological well-being
      and harmony and (2) how psychological well-being and its dimensions relate to
      harmony within the four affective profiles. Method. 500 participants (mean age =
      34.14 years, SD. = +/-12.75 years; 187 males and 313 females) were recruited
      online and required to answer three self-report measures: The Positive Affect and
      Negative Affect Schedule; The Scales of Psychological Well-Being (short version)
      and The Harmony in Life Scale. We conducted a Multivariate Analysis of Variance
      where the affective profiles and gender were the independent factors and
      psychological well-being composite score, its six dimensions as well as the
      harmony in life score were the dependent factors. In addition, we conducted four
      multi-group (i.e., the four affective profiles) moderation analyses with the
      psychological well-being dimensions as predictors and harmony in life as the
      dependent variables. Results. Individuals categorised as self-fulfilling, as
      compared to the other profiles, tended to score higher on the psychological well
      being dimensions: positive relations, environmental mastery, self-acceptance,
      autonomy, personal growth, and purpose in life. In addition, 47% to 66% of the
      variance of the harmony in life was explained by the dimensions of psychological
      well-being within the four affective profiles. Specifically, harmony in life was
      significantly predicted by environmental mastery and self-acceptance across all
      affective profiles. However, for the low affective group high purpose in life
      predicted low levels of harmony in life. Conclusions. The results demonstrated
      that affective profiles systematically relate to psychological well-being and
      harmony in life. Notably, individuals categorised as self-fulfilling tended to
      report higher levels of both psychological well-being and harmony in life when
      compared with the other profiles. Meanwhile individuals in the self-destructive
      group reported the lowest levels of psychological well-being and harmony when
      compared with the three other profiles. It is proposed that self-acceptance and
      environmental acceptance might enable individuals to go from self-destructive to
      a self-fulfilling state that also involves harmony in life. 

PMID- 24688844
TI  - Detecting deception via eyeblink frequency modulation.
AB  - To assess the efficacy of using eyeblink frequency modulation to detect deception
      about a third party, 32 participants were sent on a mission to deliver a package
      to an interviewer. 17 of the participants lied to the interviewer about the
      details of their mock mission and 15 responded truthfully. During the interview,
      eyeblink frequency data were collected via electromyography and recorded video.
      Liars displayed eyeblink frequency suppression while lying, while truth tellers
      exhibited an increase in eyeblink frequency during the mission relevant
      questioning period. The compensatory flurry of eyeblinks following deception
      observed in previous studies was absent in the present study. A discriminant
      function using eyeblink suppression to predict lying correctly classified 81.3%
      of cases, with a sensitivity of 88.2% and a specificity of 73.3%. This technique,
      yielding a reasonable sensitivity, shows promise for future testing as, unlike
      polygraph, it is compatible with distance technology. 

PMID- 24688845
TI  - Reduced object related negativity response indicates impaired auditory scene
      analysis in adults with autistic spectrum disorder.
AB  - Auditory Scene Analysis provides a useful framework for understanding atypical
      auditory perception in autism. Specifically, a failure to segregate the incoming
      acoustic energy into distinct auditory objects might explain the aversive
      reaction autistic individuals have to certain auditory stimuli or environments.
      Previous research with non-autistic participants has demonstrated the presence of
      an Object Related Negativity (ORN) in the auditory event related potential that
      indexes pre-attentive processes associated with auditory scene analysis. Also
      evident is a later P400 component that is attention dependent and thought to be
      related to decision-making about auditory objects. We sought to determine whether
      there are differences between individuals with and without autism in the levels
      of processing indexed by these components. Electroencephalography (EEG) was used
      to measure brain responses from a group of 16 autistic adults, and 16 age- and
      verbal-IQ-matched typically-developing adults. Auditory responses were elicited
      using lateralized dichotic pitch stimuli in which inter-aural timing differences
      create the illusory perception of a pitch that is spatially separated from a
      carrier noise stimulus. As in previous studies, control participants produced an
      ORN in response to the pitch stimuli. However, this component was significantly
      reduced in the participants with autism. In contrast, processing differences were
      not observed between the groups at the attention-dependent level (P400). These
      findings suggest that autistic individuals have difficulty segregating auditory
      stimuli into distinct auditory objects, and that this difficulty arises at an
      early pre-attentive level of processing. 

PMID- 24688846
TI  - Strong Stackelberg reasoning in symmetric games: An experimental replication and
      extension.
AB  - In common interest games in which players are motivated to coordinate their
      strategies to achieve a jointly optimal outcome, orthodox game theory provides no
      general reason or justification for choosing the required strategies. In the
      simplest cases, where the optimal strategies are intuitively obvious, human
      decision makers generally coordinate without difficulty, but how they achieve
      this is poorly understood. Most theories seeking to explain strategic
      coordination have limited applicability, or require changes to the game
      specification, or introduce implausible assumptions or radical departures from
      fundamental game-theoretic assumptions. The theory of strong Stackelberg
      reasoning, according to which players choose strategies that would maximize their
      own payoffs if their co-players could invariably anticipate any strategy and
      respond with a best reply to it, avoids these problems and explains strategic
      coordination in all dyadic common interest games. Previous experimental evidence
      has provided evidence for strong Stackelberg reasoning in asymmetric games. Here
      we report evidence from two experiments consistent with players being influenced
      by strong Stackelberg reasoning in a wide variety of symmetric 3 * 3 games but
      tending to revert to other choice criteria when strong Stackelberg reasoning
      generates small payoffs. 

PMID- 24688847
TI  - Ankyrin domains across the Tree of Life.
AB  - Ankyrin (ANK) repeats are one of the most common amino acid sequence motifs that
      mediate interactions between proteins of myriad sizes, shapes and functions. We
      assess their widespread abundance in Bacteria and Archaea for the first time and
      demonstrate in Bacteria that lifestyle, rather than phylogenetic history, is a
      predictor of ANK repeat abundance. Unrelated organisms that forge facultative and
      obligate symbioses with eukaryotes show enrichment for ANK repeats in comparison
      to free-living bacteria. The reduced genomes of obligate intracellular bacteria
      remarkably contain a higher fraction of ANK repeat proteins than other
      lifestyles, and the number of ANK repeats in each protein is augmented in
      comparison to other bacteria. Taken together, these results reevaluate the
      concept that ANK repeats are signature features of eukaryotic proteins and
      support the hypothesis that intracellular bacteria broadly employ ANK repeats for
      structure-function relationships with the eukaryotic host cell. 

PMID- 24688848
TI  - A global meta-analytic contrast of cushion-plant effects on plants and on
      arthropods.
AB  - Nurse plant facilitation is a commonly reported plant-plant interaction and is an
      important factor influencing community structure in stressful environments.
      Cushion plants are an example of alpine nurse plants that modify microclimatic
      conditions within their canopies to create favourable environments for other
      plants. In this meta-analysis, the facilitative effects of cushion plants was
      expanded from previous syntheses of the topic and the relative strength of
      facilitation for other plants and for arthropods were compared globally.The
      abundance, diversity, and species presence/absence effect size estimates were
      tested as plant responses to nurse plants and a composite measure was tested for
      arthropods. The strength of facilitation was on average three times greater for
      arthropods relative to all plant responses to cushions. Plant species presence,
      i.e., frequency of occurrence, was not enhanced by nurse-plants. Cushion plants
      nonetheless acted as nurse plants for both plants and arthropods in most alpine
      contexts globally, and although responses by other plant species currently
      dominate the facilitation literature, preliminary synthesis of the evidence
      suggests that the potential impacts of nurses may be even greater for other
      trophic levels. 

PMID- 24688849
TI  - System wide analyses have underestimated protein abundances and the importance of
      transcription in mammals.
AB  - Large scale surveys in mammalian tissue culture cells suggest that the protein
      expressed at the median abundance is present at 8,000-16,000 molecules per cell
      and that differences in mRNA expression between genes explain only 10-40% of the
      differences in protein levels. We find, however, that these surveys have
      significantly underestimated protein abundances and the relative importance of
      transcription. Using individual measurements for 61 housekeeping proteins to
      rescale whole proteome data from Schwanhausser et al. (2011), we find that the
      median protein detected is expressed at 170,000 molecules per cell and that our
      corrected protein abundance estimates show a higher correlation with mRNA
      abundances than do the uncorrected protein data. In addition, we estimated the
      impact of further errors in mRNA and protein abundances using direct experimental
      measurements of these errors. The resulting analysis suggests that mRNA levels
      explain at least 56% of the differences in protein abundance for the 4,212 genes
      detected by Schwanhausser et al. (2011), though because one major source of error
      could not be estimated the true percent contribution should be higher. We also
      employed a second, independent strategy to determine the contribution of mRNA
      levels to protein expression. We show that the variance in translation rates
      directly measured by ribosome profiling is only 12% of that inferred by
      Schwanhausser et al. (2011), and that the measured and inferred translation rates
      correlate poorly (R(2) = 0.13). Based on this, our second strategy suggests that
      mRNA levels explain ~81% of the variance in protein levels. We also determined
      the percent contributions of transcription, RNA degradation, translation and
      protein degradation to the variance in protein abundances using both of our
      strategies. While the magnitudes of the two estimates vary, they both suggest
      that transcription plays a more important role than the earlier studies implied
      and translation a much smaller role. Finally, the above estimates only apply to
      those genes whose mRNA and protein expression was detected. Based on a detailed
      analysis by Hebenstreit et al. (2012), we estimate that approximately 40% of
      genes in a given cell within a population express no mRNA. Since there can be no
      translation in the absence of mRNA, we argue that differences in translation
      rates can play no role in determining the expression levels for the ~40% of genes
      that are non-expressed. 

PMID- 24688850
TI  - Morphological traits: predictable responses to macrohabitats across a 300 km
      scale.
AB  - Species traits may provide a short-cut to predicting generalities in species
      turnover in response to environmental change, particularly for poorly known taxa.
      We ask if morphological traits of assemblages respond predictably to
      macrohabitats across a large scale. Ant assemblages were collected at nine paired
      pasture and remnant sites from within three areas along a 300 km distance. We
      measured ten functional morphological traits for replicate individuals of each
      species. We used a fourth corner model to test associations between microhabitat
      variables, macrohabitats (pastures and remnants) and traits. In addition, we
      tested the phylogenetic independence of traits, to determine if responses were
      likely to be due to filtering by morphology or phylogeny. Nine of ten traits were
      predicted by macrohabitat and the majority of these traits were independent of
      phylogeny. Surprisingly, microhabitat variables were not associated with
      morphological traits. Traits which were associated with macrohabitats were
      involved in locomotion, feeding behaviour and sensory ability. Ants in remnants
      had more maxillary palp segments, longer scapes and wider eyes, while having
      shorter femurs, smaller apical mandibular teeth and shorter Weber's lengths. A
      clear relationship between traits and macrohabitats across a large scale suggests
      that species are filtered by coarse environmental differences. In contrast to the
      findings of previous studies, fine-scale filtering of morphological traits was
      not apparent. If such generalities in morphological trait responses to habitat
      hold across even larger scales, traits may prove critical in predicting the
      response of species assemblages to global change. 

PMID- 24688851
TI  - Smoking close to others and butt littering at bus stops: pilot observational
      study.
AB  - Background. Transportation settings such as bus stops and train station platforms
      are increasingly the target for new smokefree legislation. Relevant issues
      include secondhand smoke exposure, nuisance, litter, fire risks and the
      normalization of smoking. We therefore aimed to pilot study aspects of smoking
      behavior and butt disposal at bus stops. Methods. Systematic observation of
      smoking and butt disposal by smokers at bus stops. The selection of 11 sites was
      a mix of convenience and purposeful (bus stops on main routes) in two New Zealand
      cities. Results. During 27 h of observation, a total of 112 lit cigarettes were
      observed being smoked. Smoking occurred in the presence of: just adults (46%),
      both young people and adults (44%), just young people (6%) and alone (5%). An
      average of 6.3 adults and 3.8 young people were present at the bus stops while
      smoking occurred, at average minimum distances of 1.7 and 2.2 m respectively. In
      bus stops that included an enclosed shelter, 33% of the cigarettes were smoked
      inside the shelter with others present. Littering was the major form of cigarette
      disposal with 84% of cigarettes smoked being littered (95% CI; 77%-90%). Also, 4%
      of disposals were into vegetation, which may pose a fire risk. Conclusions. This
      pilot study is limited by its small size and various methodological aspects but
      it appears to be a first attempt to provide observational evidence around smoking
      at bus stops. The issues described could be considered by policy makers who are
      investigating national smokefree laws or by-laws covering transportation
      settings. 

PMID- 24688852
TI  - Occurrence of twin embryos in the eastern bluebird.
AB  - We report the first record of presumed twinning in eastern bluebird (Sialia
      sialis) and provide a review of previously reported twinning events in wild
      birds. A nest containing twin eastern bluebird nestlings was monitored in 2013 in
      central Pennsylvania and reported to the Cornell Lab of Ornithology's NestWatch
      program, a national program where volunteers submit data on wild nesting birds. A
      presumed double-yolked egg of a free-living eastern bluebird pair hatched
      successfully, and twin nestlings lived for 11 days in a nest box shared by three
      siblings. Due to the rarity of twinning in wild birds, engaging the public to
      monitor large numbers of nests is the most likely approach to documenting
      twinning in wild populations, and citizen science provides the infrastructure for
      individuals to share observations. 

PMID- 24688853
TI  - Evidence for protection of targeted reef fish on the largest marine reserve in
      the Caribbean.
AB  - Marine reserves can restore fish abundance and diversity in areas impacted by
      overfishing, but the effectiveness of reserves in developing countries where
      resources for enforcement are limited, have seldom been evaluated. Here we assess
      whether the establishment in 1996 of the largest marine reserve in the Caribbean,
      Gardens of the Queen in Cuba, has had a positive effect on the abundance of
      commercially valuable reef fish species in relation to neighboring unprotected
      areas. We surveyed 25 sites, including two reef habitats (reef crest and reef
      slope), inside and outside the marine reserve, on five different months, and over
      a one-and-a-half year period. Densities of the ten most frequent, highly
      targeted, and relatively large fish species showed a significant variability
      across the archipelago for both reef habitats that depended on the month of
      survey. These ten species showed a tendency towards higher abundance inside the
      reserve in both reef habitats for most months during the study. Average fish
      densities pooled by protection level, however, showed that five out of these ten
      species were at least two-fold significantly higher inside than outside the
      reserve at one or both reef habitats. Supporting evidence from previously
      published studies in the area indicates that habitat complexity and major benthic
      communities were similar inside and outside the reserve, while fishing pressure
      appeared to be homogeneous across the archipelago before reserve establishment.
      Although poaching may occur within the reserve, especially at the boundaries,
      effective protection from fishing was the most plausible explanation for the
      patterns observed. 

PMID- 24688854
TI  - Biblio-MetReS for user-friendly mining of genes and biological processes in
      scientific documents.
AB  - One way to initiate the reconstruction of molecular circuits is by using
      automated text-mining techniques. Developing more efficient methods for such
      reconstruction is a topic of active research, and those methods are typically
      included by bioinformaticians in pipelines used to mine and curate large
      literature datasets. Nevertheless, experimental biologists have a limited number
      of available user-friendly tools that use text-mining for network reconstruction
      and require no programming skills to use. One of these tools is Biblio-MetReS.
      Originally, this tool permitted an on-the-fly analysis of documents contained in
      a number of web-based literature databases to identify co-occurrence of
      proteins/genes. This approach ensured results that were always up-to-date with
      the latest live version of the databases. However, this 'up-to-dateness' came at
      the cost of large execution times. Here we report an evolution of the application
      Biblio-MetReS that permits constructing co-occurrence networks for genes, GO
      processes, Pathways, or any combination of the three types of entities and
      graphically represent those entities. We show that the performance of Biblio
      MetReS in identifying gene co-occurrence is as least as good as that of other
      comparable applications (STRING and iHOP). In addition, we also show that the
      identification of GO processes is on par to that reported in the latest
      BioCreAtIvE challenge. Finally, we also report the implementation of a new
      strategy that combines on-the-fly analysis of new documents with preprocessed
      information from documents that were encountered in previous analyses. This
      combination simultaneously decreases program run time and maintains 'up-to
      dateness' of the results. AVAILABILITY:
      http://metres.udl.cat/index.php/downloads, CONTACT: metres.cmb@gmail.com.

PMID- 24688855
TI  - FragBuilder: an efficient Python library to setup quantum chemistry calculations
      on peptides models.
AB  - We present a powerful Python library to quickly and efficiently generate
      realistic peptide model structures. The library makes it possible to quickly set
      up quantum mechanical calculations on model peptide structures. It is possible to
      manually specify a specific conformation of the peptide. Additionally the library
      also offers sampling of backbone conformations and side chain rotamer
      conformations from continuous distributions. The generated peptides can then be
      geometry optimized by the MMFF94 molecular mechanics force field via convenient
      functions inside the library. Finally, it is possible to output the resulting
      structures directly to files in a variety of useful formats, such as XYZ or PDB
      formats, or directly as input files for a quantum chemistry program. FragBuilder
      is freely available at https://github.com/jensengroup/fragbuilder/ under the
      terms of the BSD open source license. 

PMID- 24688856
TI  - Asian elephants (Elephas maximus) reassure others in distress.
AB  - Contact directed by uninvolved bystanders toward others in distress, often termed
      consolation, is uncommon in the animal kingdom, thus far only demonstrated in the
      great apes, canines, and corvids. Whereas the typical agonistic context of such
      contact is relatively rare within natural elephant families, other causes of
      distress may trigger similar, other-regarding responses. In a study carried out
      at an elephant camp in Thailand, we found that elephants affiliated significantly
      more with other individuals through directed, physical contact and vocal
      communication following a distress event than in control periods. In addition,
      bystanders affiliated with each other, and matched the behavior and emotional
      state of the first distressed individual, suggesting emotional contagion. The
      initial distress responses were overwhelmingly directed toward ambiguous stimuli,
      thus making it difficult to determine if bystanders reacted to the distressed
      individual or showed a delayed response to the same stimulus. Nonetheless, the
      directionality of the contacts and their nature strongly suggest attention toward
      the emotional states of conspecifics. The elephants' behavior is therefore best
      classified with similar consolation responses by apes, possibly based on
      convergent evolution of empathic capacities. 

PMID- 24688857
TI  - Artificial light and nocturnal activity in gammarids.
AB  - Artificial light is gaining attention as a potential stressor to aquatic
      ecosystems. Artificial lights located near streams increase light levels
      experienced by stream invertebrates and we hypothesized light would depress night
      drift rates. We also hypothesized that the effect of light on drift rates would
      decrease over time as the invertebrates acclimated to the new light level over
      the course of one month's exposure. These hypotheses were tested by placing
      Gammarus spp. in eight, 75 m * 1 m artificial flumes. One flume was exposed to
      strong (416 lx) artificial light at night. This strong light created a gradient
      between 4.19 and 0.04 lx over the neighboring six artificial flumes, while a
      control flume was completely covered with black plastic at night. Night-time
      light measurements taken in the Berlin area confirm that half the flumes were at
      light levels experienced by urban aquatic invertebrates. Surprisingly, no light
      treatment affected gammarid drift rates. In contrast, physical activity
      measurements of in situ individually caged G. roeseli showed they increased short
      term activity levels in nights of complete darkness and decreased activity levels
      in brightly lit flumes. Both nocturnal and diurnal drift increased, and day drift
      rates were unexpectadly higher than nocturnal drift. 

PMID- 24688858
TI  - Expression profiles of the immune genes CD4, CD8beta, IFNgamma, IL-4, IL-6 and IL
      10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR.
AB  - Investigation of the immune response of the koala (Phascolarctos cinereus) is
      needed urgently, but has been limited by scarcity of species-specific reagents
      and methods for this unique and divergent marsupial. Infectious disease is an
      important threat to wild populations of koalas; the most widespread and important
      of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia
      pneumoniae. In addition, koala retrovirus (KoRV), which is of 100% prevalence in
      northern Australia, has been proposed as an important agent of immune suppression
      that could explain the koala's susceptibility to disease. The correct balance of
      T regulatory, T helper 1 (Th1) and Th2 lymphocyte responses are important to an
      individual's susceptibility or resistance to chlamydial infection. The ability to
      study chlamydial or KoRV pathogenesis, effects of environmental stressors on
      immunity, and the response of koalas to vaccines under development, by examining
      the koala's adaptive response to natural infection or in-vitro stimulation, has
      been limited to date by a paucity of species- specific reagents. In this study we
      have used cytokine sequences from four marsupial genomes to identify mRNA
      sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4),
      interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNgamma)
      along with CD4 and CD8beta. The koala sequences used for primer design showed
      >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78%
      with Tasmanian devil amino acid sequences. We report the development of real-time
      RT-PCR assays to measure the expression of these genes in unstimulated cells and
      after three common mitogen stimulation protocols (phorbol myristate
      acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin
      A). Phorbol myristate acetate/ionomycin was found to be the most effective
      mitogen to up-regulate the production of IL-4, IL-10 and IFNgamma. IL-6
      production was not consistently up-regulated by any of the protocols. Expression
      of CD4 and CD8beta was down-regulated by mitogen stimulation. We found that the
      reference genes GAPDH and 28s are valid for normalising cytokine expression by
      koala lymphocytes after mitogen stimulation. 

PMID- 24688859
TI  - Poppr: an R package for genetic analysis of populations with clonal, partially
      clonal, and/or sexual reproduction.
AB  - Many microbial, fungal, or oomcyete populations violate assumptions for
      population genetic analysis because these populations are clonal, admixed,
      partially clonal, and/or sexual. Furthermore, few tools exist that are
      specifically designed for analyzing data from clonal populations, making analysis
      difficult and haphazard. We developed the R package poppr providing unique tools
      for analysis of data from admixed, clonal, mixed, and/or sexual populations.
      Currently, poppr can be used for dominant/codominant and haploid/diploid genetic
      data. Data can be imported from several formats including GenAlEx formatted text
      files and can be analyzed on a user-defined hierarchy that includes unlimited
      levels of subpopulation structure and clone censoring. New functions include
      calculation of Bruvo's distance for microsatellites, batch-analysis of the index
      of association with several indices of genotypic diversity, and graphing
      including dendrograms with bootstrap support and minimum spanning networks. While
      functions for genotypic diversity and clone censoring are specific for clonal
      populations, several functions found in poppr are also valuable to analysis of
      any populations. A manual with documentation and examples is provided. Poppr is
      open source and major releases are available on CRAN: http://cran.r
      project.org/package=poppr. More supporting documentation and tutorials can be
      found under 'resources' at: http://grunwaldlab.cgrb.oregonstate.edu/. 

PMID- 24688860
TI  - Gamma-H2AX biodosimetry for use in large scale radiation incidents: comparison of
      a rapid '96 well lyse/fix' protocol with a routine method.
AB  - Following a radiation incident, preliminary dose estimates made by gamma-H2AX
      foci analysis can supplement the early triage of casualties based on clinical
      symptoms. Sample processing time is important when many individuals need to be
      rapidly assessed. A protocol was therefore developed for high sample throughput
      that requires less than 0.1 ml blood, thus potentially enabling finger prick
      sampling. The technique combines red blood cell lysis and leukocyte fixation in
      one step on a 96 well plate, in contrast to the routine protocol, where
      lymphocytes in larger blood volumes are typically separated by Ficoll density
      gradient centrifugation with subsequent washing and fixation steps. The rapid '96
      well lyse/fix' method reduced the estimated sample processing time for 96 samples
      to about 4 h compared to 15 h using the routine protocol. However, scoring 20
      cells in 96 samples prepared by the rapid protocol took longer than for the
      routine method (3.1 versus 1.5 h at zero dose; 7.0 versus 6.1 h for irradiated
      samples). Similar foci yields were scored for both protocols and consistent dose
      estimates were obtained for samples exposed to 0, 0.2, 0.6, 1.1, 1.2, 2.1 and 4.3
      Gy of 250 kVp X-rays at 0.5 Gy/min and incubated for 2 h. Linear regression
      coefficients were 0.87 +/- 0.06 (R (2) = 97.6%) and 0.85 +/- 0.05 (R (2) = 98.3%)
      for estimated versus actual doses for the routine and lyse/fix method,
      respectively. The lyse/fix protocol can therefore facilitate high throughput
      processing for gamma-H2AX biodosimetry for use in large scale radiation
      incidents, at the cost of somewhat longer foci scoring times. 

PMID- 24688861
TI  - Personality predicts the propensity for social learning in a wild primate.
AB  - Social learning can play a critical role in the reproduction and survival of
      social animals. Individual differences in the propensity for social learning are
      therefore likely to have important fitness consequences. We asked whether
      personality might underpin such individual variation in a wild population of
      chacma baboons (Papio ursinus). We used two field experiments in which
      individuals had the opportunity to learn how to solve a task from an experienced
      conspecific demonstrator: exploitation of a novel food and a hidden item of known
      food. We investigated whether the (1) time spent watching a demonstrator and (2)
      changes in task-solving behaviour after watching a demonstrator were related to
      personality. We found that both boldness and anxiety influenced individual
      performance in social learning. Specifically, bolder and more anxious animals
      were more likely to show a greater improvement in task solving after watching a
      demonstrator. In addition, there was also evidence that the acquisition of social
      information was not always correlated with its use. These findings present new
      insights into the costs and benefits of different personality types, and have
      important implications for the evolution of social learning. 

PMID- 24688862
TI  - Lack of quantitative training among early-career ecologists: a survey of the
      problem and potential solutions.
AB  - Proficiency in mathematics and statistics is essential to modern ecological
      science, yet few studies have assessed the level of quantitative training
      received by ecologists. To do so, we conducted an online survey. The 937
      respondents were mostly early-career scientists who studied biology as
      undergraduates. We found a clear self-perceived lack of quantitative training:
      75% were not satisfied with their understanding of mathematical models; 75% felt
      that the level of mathematics was "too low" in their ecology classes; 90% wanted
      more mathematics classes for ecologists; and 95% more statistics classes.
      Respondents thought that 30% of classes in ecology-related degrees should be
      focused on quantitative disciplines, which is likely higher than for most
      existing programs. The main suggestion to improve quantitative training was to
      relate theoretical and statistical modeling to applied ecological problems.
      Improving quantitative training will require dedicated, quantitative classes for
      ecology-related degrees that contain good mathematical and statistical practice. 

PMID- 24688863
TI  - Ant-mediated seed dispersal in a warmed world.
AB  - Climate change affects communities both directly and indirectly via changes in
      interspecific interactions. One such interaction that may be altered under
      climate change is the ant-plant seed dispersal mutualism common in deciduous
      forests of eastern North America. As climatic warming alters the abundance and
      activity levels of ants, the potential exists for shifts in rates of ant-mediated
      seed dispersal. We used an experimental temperature manipulation at two sites in
      the eastern US (Harvard Forest in Massachusetts and Duke Forest in North
      Carolina) to examine the potential impacts of climatic warming on overall rates
      of seed dispersal (using Asarum canadense seeds) as well as species-specific
      rates of seed dispersal at the Duke Forest site. We also examined the
      relationship between ant critical thermal maxima (CTmax) and the mean seed
      removal temperature for each ant species. We found that seed removal rates did
      not change as a result of experimental warming at either study site, nor were
      there any changes in species-specific rates of seed dispersal. There was,
      however, a positive relationship between CTmax and mean seed removal temperature,
      whereby species with higher CTmax removed more seeds at hotter temperatures. The
      temperature at which seeds were removed was influenced by experimental warming as
      well as diurnal and day-to-day fluctuations in temperature. Taken together, our
      results suggest that while temperature may play a role in regulating seed removal
      by ants, ant plant seed-dispersal mutualisms may be more robust to climate change
      than currently assumed. 

PMID- 24688864
TI  - Disorder affects judgements about a neighbourhood: police presence does not.
AB  - Many police forces operate a policy of high visibility in disordered
      neighbourhoods with high crime. However, little is known about whether increased
      police presence influences people's beliefs about a neighbourhood's social
      environment or their fear of crime. Three experimental studies compared people's
      perceptions of social capital and fear of crime in disordered and ordered
      neighbourhoods, either with a police presence or no police presence. In all
      studies, neighbourhood disorder lowered perceptions of social capital, resulting
      in a higher fear of crime. Police presence or absence had no significant effect.
      The pervasive effects of disorder above other environmental cues are discussed. 

PMID- 24688865
TI  - Evolutionary history determines how plant productivity responds to phylogenetic
      diversity and species richness.
AB  - The relationship between biodiversity and ecosystem function has received a great
      deal of attention in ecological research and recent results, from re-analyses,
      suggest that ecosystem function improves with increases in phylogenetic
      diversity. However, many of these results have been generalized across a range of
      different species and clades, and plants with different evolutionary histories
      could display different relationships between biodiversity and ecosystem
      function. To experimentally test this hypothesis, we manipulated species richness
      and phylogenetic diversity using 26 species from two subgenera of the genus
      Eucalyptus (subgenus Eucalyptus and subgenus Symphyomyrtus). We found that plant
      biomass (a measurement of ecosystem function) sometimes, but not always,
      responded to increases in species richness and phylogenetic diversity.
      Specifically, Symphyomyrtus plants showed a positive response while no comparable
      effect was observed for Eucalyptus plants, showing that responses to biodiversity
      can vary across different phylogenetic groups. Our results show that the impacts
      of evolutionary history may complicate the relationship between the diversity of
      plant communities and plant biomass. 

PMID- 24688866
TI  - Happy software developers solve problems better: psychological measurements in
      empirical software engineering.
AB  - For more than thirty years, it has been claimed that a way to improve software
      developers' productivity and software quality is to focus on people and to
      provide incentives to make developers satisfied and happy. This claim has rarely
      been verified in software engineering research, which faces an additional
      challenge in comparison to more traditional engineering fields: software
      development is an intellectual activity and is dominated by often-neglected human
      factors (called human aspects in software engineering research). Among the many
      skills required for software development, developers must possess high analytical
      problem-solving skills and creativity for the software construction process.
      According to psychology research, affective states-emotions and moods-deeply
      influence the cognitive processing abilities and performance of workers,
      including creativity and analytical problem solving. Nonetheless, little research
      has investigated the correlation between the affective states, creativity, and
      analytical problem-solving performance of programmers. This article echoes the
      call to employ psychological measurements in software engineering research. We
      report a study with 42 participants to investigate the relationship between the
      affective states, creativity, and analytical problem-solving skills of software
      developers. The results offer support for the claim that happy developers are
      indeed better problem solvers in terms of their analytical abilities. The
      following contributions are made by this study: (1) providing a better
      understanding of the impact of affective states on the creativity and analytical
      problem-solving capacities of developers, (2) introducing and validating
      psychological measurements, theories, and concepts of affective states,
      creativity, and analytical-problem-solving skills in empirical software
      engineering, and (3) raising the need for studying the human factors of software
      engineering by employing a multidisciplinary viewpoint. 

PMID- 24688867
TI  - 'Mystery big cats' in the Peruvian Amazon: morphometrics solve a cryptozoological
      mystery.
AB  - Two big cat skulls procured from hunters of Yanachaga National Park, Peru, were
      reported as those of cats informally dubbed the 'striped tiger' and 'anomalous
      jaguar'. Observations suggested that both skulls were distinct from those of
      jaguars, associated descriptions of integument did not conform to this species,
      and it has been implied that both represent members of one or two novel species.
      We sought to resolve the identity of the skulls using morphometrics. DNA could
      not be retrieved since both had been boiled as part of the defleshing process. We
      took 36 cranial and 13 mandibular measurements and added them to a database
      incorporating nearly 300 specimens of over 30 felid species. Linear discriminant
      analysis resolved both specimens as part of Panthera onca with high probabilities
      for cranial and mandibular datasets. Furthermore, the specimens exhibit
      characters typical of jaguars. If the descriptions of their patterning and
      pigmentation are accurate, we assume that both individuals were aberrant. 

PMID- 24688868
TI  - A review of the Zoogonidae (Digenea: Microphalloidea) from fishes of the waters
      around New Caledonia, with the description of Overstreetia cribbi n. sp.
AB  - New and published reports of zoogonid digeneans from New Caledonian waters are
      recorded, including a description of Overstreetia cribbi n. sp. from
      Atherinomorus lacunosus. This species differs from its congeners in the detail of
      its circum-oral spination and some metrical features. Other new records are of:
      Diphterostomum plectorhynchi Machida, Kamegai & Kuramochi, 2006 in Diagramma
      pictum; Parvipyrum acanthuri (Pritchard, 1963) in Acanthurus dussumieri;
      Zoogonoides viviparus (Olsson, 1868) in Lagocephalus sceleratus; Deretrema ?
      combesorum (Bray & Justine, 2008a; Bray & Justine, 2008b) early ovigerous forms
      in Parupeneus pleurostigma; D? acutum (Pritchard, 1963) in P. barberinus; and an
      unidentified immature zoogonid in P. multifasciatus. The newly reported specimens
      are illustrated and measurements given. The distribution of New Caledonian
      zoogonids is listed. 

PMID- 24688869
TI  - Disturbance and climatic effects on red spruce community dynamics at its southern
      continuous range margin.
AB  - Red spruce (Picea rubens) populations experienced a synchronous rangewide decline
      in growth and vigor starting in the 1960s, likely caused by climate change and a
      combination of environmental disturbances. However, it is not yet known if
      populations continue to decline or have recovered. Red spruce growing near its
      southern range margin in Massachusetts is a species of concern, in light of the
      vulnerability to climate change. This study uses population data from 17
      permanent plots coupled with tree-ring data to examine radial growth rates,
      determine the growth-climate relationship, and document disturbance events. Red
      spruce at these plots ranged from 90 to 184 years old, and comprised 15 to 29
      m(2)/ha basal area. Red spruce seedlings and saplings were common at plots with
      previously high overstory spruce abundance, indicating it could return to a more
      dominant position under favorable growing conditions. However, permanent plot
      measures over a 50 year time span did not indicate any consistent trends for
      changes in basal area or density for red spruce or other woody species. Climate
      data show that mean annual minimum, maximum, and summer temperatures have
      increased over the last 100 years. Dendroclimatological analyses indicated that
      red spruce growth was sensitive to both temperature and precipitation. Prior to
      the 1960s, spruce at these sites showed a positive response to precipitation;
      however after a multi-year drought in the 1960s showed an increasingly negative
      correlation with precipitation. There has been a negative growth response to
      regional warming, as spruce radial growth was mostly constrained by increasing
      temperatures, potentially coupled with the associated increasing drought-dress. I
      suggest the change in climate response is potentially due to a physiological
      threshold response to increasing temperatures, which may cause spruce to continue
      to decline or be lost from the lower elevation sites, while the high elevation
      sites has a persistent spruce population. 

PMID- 24688871
TI  - The avian fossil record in Insular Southeast Asia and its implications for avian
      biogeography and palaeoecology.
AB  - Excavations and studies of existing collections during the last decades have
      significantly increased the abundance as well as the diversity of the avian
      fossil record for Insular Southeast Asia. The avian fossil record covers the
      Eocene through the Holocene, with the majority of bird fossils Pleistocene in
      age. Fossil bird skeletal remains represent at least 63 species in 54 genera and
      27 families, and two ichnospecies are represented by fossil footprints. Birds of
      prey, owls and swiftlets are common elements. Extinctions seem to have been few,
      suggesting continuity of avian lineages since at least the Late Pleistocene,
      although some shifts in species ranges have occurred in response to climatic
      change. Similarities between the Late Pleistocene avifaunas of Flores and Java
      suggest a dispersal route across southern Sundaland. Late Pleistocene assemblages
      of Niah Cave (Borneo) and Liang Bua (Flores) support the rainforest refugium
      hypothesis in Southeast Asia as they indicate the persistence of forest cover, at
      least locally, throughout the Late Pleistocene and Holocene. 

PMID- 24688870
TI  - Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30
      year prospective follow-up study.
AB  - Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological
      damage, but serious consequences are effectively controlled by phototherapy and
      blood exchange transfusion. HB is still a serious health problem in economically
      compromised parts of the world. The long term outcome has been regarded favorable
      based on epidemiological data, but has not been confirmed in prospective follow
      up studies extending to adulthood. Methods. We studied the long term consequences
      of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases
      are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30
      years of age. HB cases were newborns >= 2500 g birth weight and >= 37 weeks of
      gestation who had bilirubin concentrations > 340 umol/l or required blood
      exchange transfusion. Subjects with HB were divided into subgroups based on the
      presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral
      disorders in childhood, and compared with healthy controls. Subjects were seen at
      discharge, 5, 9 and 16 years of life and parent's and teacher's assessments were
      recorded. At 30 years they filled a questionnaire about academic and occupational
      achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD
      self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading
      and writing tests at 9 years of life. Results. Compared to controls, the odds for
      a child with HB having neurobehavioral symptoms at 9 years was elevated (OR =
      4.68). Forty-five per cent of the HB group were affected by cognitive
      abnormalities in childhood and continued to experience problems in adulthood.
      This was apparent in academic achievement (p < 0.0001) and the ability to
      complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the
      subgroup of affected HB reported persisting cognitive complaints e.g., problems
      with reading, writing and mathematics. Childhood symptoms of
      hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more
      common in HB groups, but in adulthood the symptoms were equal. The affected HB
      had lower scores in parameters reflecting life satisfaction, less controlled
      drinking, but not increased substance abuse. Discussion. Our results indicate
      that neonatal HB has negative consequences in adult age. A prospectively
      collected cohort with strict inclusion criteria enables to control most of the
      bias factors involved with retrospective data. The control and HB groups were
      remarkably similar at birth in terms of medical data, and the growth environment
      of the children, as well as the parents' social groups, education, size of
      family, type of housing at birth and at 9 years of age. Our findings bear
      resemblance to disorders of the fronto-striatal network, and also symptoms of the
      ADHD spectrum were frequent in the HB group suggesting a link of HB to other
      neurodevelopmental disorders. 

PMID- 24688872
TI  - Ecological distribution of protosteloid amoebae in New Zealand.
AB  - During the period of March 2004 to December 2007, samples of aerial litter (dead
      but still attached plant parts) and ground litter (dead plant material on the
      ground) were collected from 81 study sites representing a wide range of latitudes
      (34 degrees S to 50 degrees S) and a variety of different types of habitats
      throughout New Zealand (including Stewart Island and the Auckland Islands). The
      objective was to survey the assemblages of protosteloid amoebae present in this
      region of the world. Twenty-nine described species of protosteloid amoebae were
      recorded by making morphological identifications of protosteloid amoebae fruiting
      bodies on cultured substrates. Of the species observed, Protostelium mycophaga
      was by far the most abundant and was found in more than half of all samples. Most
      species were found in fewer than 10% of the samples collected. Seven abundant or
      common species were found to display significantly increased likelihood for
      detection in aerial litter or ground litter microhabitats. There was some
      evidence of a general correlation between environmental factors - annual
      precipitation, elevation, and distance from the equator (latitude) - and the
      abundance and richness of protosteloid amoebae. An increase in each of these
      three factors correlated with a decrease in both abundance and richness. This
      study provides a thorough survey of the protosteloid amoebae present in New
      Zealand and adds to a growing body of evidence which suggests several
      correlations between their broad distributional patterns and environmental
      factors. 

PMID- 24688873
TI  - The invasive New Guinea flatworm Platydemus manokwari in France, the first record
      for Europe: time for action is now.
AB  - Non-indigenous terrestrial flatworms (Platyhelminthes) have been recorded in
      thirteen European countries. They include Bipalium kewense and Dolichoplana
      striata that are largely restricted to hothouses and may be regarded as non
      invasive species. In addition there are species from the southern hemisphere such
      as the invasive New Zealand flatworm Arthurdendyus triangulatus in the United
      Kingdom, Eire and the Faroe Islands, the Australian flatworm Australoplana
      sanguinea alba in Eire and the United Kingdom, and the Australian Blue Garden
      flatworm Caenoplana coerulea in France, Menorca and the United Kingdom. The
      United Kingdom has some twelve or more non-indigenous species most of which are
      Australian and New Zealand species. These species may move to an invasive stage
      when optimum environmental and other conditions occur, and the flatworms then
      have the potential to cause economic or environmental harm. In this paper, we
      report the identification (from morphology and molecular analysis of COI
      sequences) of non-indigenous terrestrial flatworms found in a hothouse in Caen
      (France) as the New Guinea flatworm Platydemus manokwari de Beauchamp, 1963
      (Platyhelminthes, Continenticola, Geoplanidae, Rhynchodeminae). Platydemus
      manokwari is among the "100 World's Worst Invader Alien Species". Lists of World
      geographic records, prey in the field and prey in laboratories of P. manokwari
      are provided. This species is considered a threat to native snails wherever it is
      introduced. The recent discovery of P. manokwari in France represents a
      significant extension of distribution of this Invasive Alien Species from the
      Indo-Pacific region to Europe. If it escaped the hothouse, the flatworm might
      survive winters and become established in temperate countries. The existence of
      this species in France requires an early warning of this incursion to State and
      European Union authorities, followed by the eradication of the flatworm in its
      locality, tightening of internal quarantine measures to prevent further spread of
      the flatworm to and from this site, identifying if possible the likely primary
      source of the flatworm, and tracing other possible incursions that may have
      resulted from accidental dispersal of plants and soil from the site. 

PMID- 24688874
TI  - The role of transcriptional regulation in maintaining the availability of
      mycobacterial adenylate cyclases.
AB  - Mycobacterium species have a complex cAMP regulatory network indicated by the
      high number of adenylate cyclases annotated in their genomes. However the need
      for a high level of redundancy in adenylate cyclase genes remains unknown. We
      have used semiquantitiative RT-PCR to examine the expression of eight
      Mycobacterium smegmatis cyclases with orthologs in the human pathogen
      Mycobacterium tuberculosis, where cAMP has recently been shown to be important
      for virulence. All eight cyclases were transcribed in all environments tested,
      and only four demonstrated environmental-mediated changes in transcription. M.
      smegmatis genes MSMEG_0545 and MSMEG_4279 were upregulated during starvation
      conditions while MSMEG_0545 and MSMEG_4924 were downregulated in H2O2 and
      MSMEG_3780 was downregulated in low pH and starvation. Promoter fusion constructs
      containing M. tuberculosis H37Rv promoters showed consistent regulation compared
      to their M. smegmatis orthologs. Overall our findings indicate that while low
      levels of transcriptional regulation occur, regulation at the mRNA level does not
      play a major role in controlling cellular cyclase availability in a given
      environment. 

PMID- 24688875
TI  - Thirty years of coral reef change in relation to coastal construction and
      increased sedimentation at Pelekane Bay, Hawai'i.
AB  - Coral reefs are being critically impacted by anthropogenic processes throughout
      the world. Long term monitoring is essential to the understanding of coral reef
      response to human impacts and the effectiveness of corrective management efforts.
      Here we reevaluated a valuable coral reef baseline established in Pelekane Bay,
      Hawai'i during 1976 and subsequently resurveyed in 1996. During this time
      interval substantial impacts occurred followed by extensive corrective measures.
      Coral and fish communities showed dramatic declines from 1977 to 1996 due to
      massive harbor construction and suboptimal land management practices on the
      watershed. More recently, corrective measures in the form of watershed
      stabilization and fishing regulations have been implemented. Consequently our
      2012 survey reveals that coral cover since 1996 has increased slightly
      accompanied by a significant increase in fish abundance, diversity, and evenness.
      This improvement can be attributed to lower fishing pressure since 1996 due to
      reduced shoreline access, tighter fishing regulations and increased monitoring of
      legal and illegal fishing activities. Stabilization of the coral community can be
      attributed partially to reduced sedimentation resulting from watershed
      restoration that included installation of sediment check dams, control of feral
      ungulates, controlled grazing and replanting of native vegetation. Insights into
      the mechanism that removes sediment from reefs was provided by a major storm
      event and a tsunami that remobilized and flushed out sediment deposits. The
      increase in herbivorous fishes probably played a role in reducing algal
      competition in favor of corals. The data suggest that the precipitous reef
      decline in this area has been arrested and offers support for the corrective
      actions previously undertaken. 

PMID- 24688876
TI  - Brain size varies with temperature in vertebrates.
AB  - The tremendous variation in brain size among vertebrates has long been thought to
      be related to differences in species' metabolic rates. It is thought that species
      with higher metabolic rates can supply more energy to support the relatively high
      cost of brain tissue. And yet, while body temperature is known to be a major
      determinant of metabolic rate, the possible effects of temperature on brain size
      have scarcely been explored. Thus, here we explore the effects of temperature on
      brain size among diverse vertebrates (fishes, amphibians, reptiles, birds and
      mammals). We find that, after controlling for body size, brain size increases
      exponentially with temperature in much the same way as metabolic rate. These
      results suggest that temperature-dependent changes in aerobic capacity, which
      have long been known to affect physical performance, similarly affect brain size.
      The observed temperature-dependence of brain size may explain observed gradients
      in brain size among both ectotherms and endotherms across broad spatial and
      temporal scales. 

PMID- 24688877
TI  - Upward nitrate transport by phytoplankton in oceanic waters: balancing nutrient
      budgets in oligotrophic seas.
AB  - In oceanic subtropical gyres, primary producers are numerically dominated by
      small (1-5 um diameter) pro- and eukaryotic cells that primarily utilize recycled
      nutrients produced by rapid grazing turnover in a highly efficient microbial
      loop. Continuous losses of nitrogen (N) to depth by sinking, either as single
      cells, aggregates or fecal pellets, are balanced by both nitrate inputs at the
      base of the euphotic zone and N2-fixation. This input of new N to balance export
      losses (the biological pump) is a fundamental aspect of N cycling and central to
      understanding carbon fluxes in the ocean. In the Pacific Ocean, detailed N
      budgets at the time-series station HOT require upward transport of nitrate from
      the nutricline (80-100 m) into the surface layer (~0-40 m) to balance
      productivity and export needs. However, concentration gradients are negligible
      and cannot support the fluxes. Physical processes can inject nitrate into the
      base of the euphotic zone, but the mechanisms for transporting this nitrate into
      the surface layer across many 10s of m in highly stratified systems are unknown.
      In these seas, vertical migration by the very largest (10(2)-10(3) um diameter)
      phytoplankton is common as a survival strategy to obtain N from sub-euphotic zone
      depths. This vertical migration is driven by buoyancy changes rather than by
      flagellated movement and can provide upward N transport as nitrate (mM
      concentrations) in the cells. However, the contribution of vertical migration to
      nitrate transport has been difficult to quantify over the required basin scales.
      In this study, we use towed optical systems and isotopic tracers to show that
      migrating diatom (Rhizosolenia) mats are widespread in the N. Pacific Ocean from
      140 degrees W to 175 degrees E and together with other migrating phytoplankton
      (Ethmodiscus, Halosphaera, Pyrocystis, and solitary Rhizosolenia) can mediate
      time-averaged transport of N (235 umol N m(-2) d(-1)) equivalent to eddy nitrate
      injections (242 umol NO3 (-) m(-2) d(-1)). This upward biotic transport can close
      N budgets in the upper 250 m of the central Pacific Ocean and together with
      diazotrophy creates a surface zone where biological nutrient inputs rather than
      physical processes dominate the new N flux. In addition to these numerically rare
      large migrators, there is evidence in the literature of ascending behavior in
      small phytoplankton that could contribute to upward flux as well. Although
      passive downward movement has dominated models of phytoplankton flux, there is
      now sufficient evidence to require a rethinking of this paradigm. Quantifying
      these fluxes is a challenge for the future and requires a reexamination of
      individual phytoplankton sinking rates as well as methods for capturing and
      enumerating ascending phytoplankton in the sea. 

PMID- 24688878
TI  - A happier and less sinister past, a more hedonistic and less fatalistic present
      and a more structured future: time perspective and well-being.
AB  - Background. Previous studies have established a link between how people relate to
      their past, present, and future (i.e., time perspective) and subjective well
      being (i.e., life satisfaction, positive and negative affect). Time perspective
      comprises five dimensions: Past Positive, Past Negative, Present Hedonistic,
      Present Fatalistic, and Future. Life satisfaction can also be evaluated in
      relation to different time frames. Moreover, approach related positive affect is
      associated to a different concept of well-being labeled psychological well-being.
      In the present study we extend previous findings by investigating the effect of
      time perspective on the time frame of evaluations of life satisfaction (past,
      present, future) and by investigating the relationship between time perspective
      and psychological well-being. Method. Questionnaires on time perspective
      (Zimbardo's Time Perspective Inventory), temporal life satisfaction (Temporal
      Satisfaction with Life Scale), affect (Positive Affect and Negative Affect
      Schedule), and psychological well-being (Scales of Psychological Well-Being-short
      version) were answered by 453 individuals. Two different structural equation
      models were tested, one of the relationship between time perspective and temporal
      life satisfaction, and the other of the relationship between time perspective,
      affect and psychological well-being. Results. Time perspective affected life
      satisfaction depending on the time scale on which it was evaluated-memory of a
      negative past influenced life satisfaction in all time frames, and a positive
      view of the past influenced both past and future life satisfaction. Moreover,
      less rumination about past negative events (i.e., low score on Past Negative),
      the tendency to take risks in the present to achieve happy feelings and/or avoid
      boredom (i.e., high scores on Present Hedonistic), and a less hopeless and
      pessimistic view about the present (low scores on Present Fatalistic) were
      associated with higher levels of psychological well-being and positive affect.
      These same time perspective dimensions were associated with lower levels of
      negative affect. The Future time perspective dimension (i.e., approaching life
      with self-control, punctuality, and planning for the future) was associated with
      both psychological well-being and positive affect. Conclusions. High levels of
      both subjective and psychological well-being are related to a happier and a less
      sinister past, a more hedonistic and less fatalistic present, as well as to a
      more structured future. 

PMID- 24688879
TI  - Description of the cascade of care and factors associated with attrition before
      and after initiating antiretroviral therapy of HIV infected children in a cohort
      study in India.
AB  - In low- and middle-income countries, the attrition across the continuum of care
      of HIV infected children is not well known. The aim of this study was to
      investigate predictors of mortality and loss to follow up (LTFU) in HIV infected
      children from a cohort study in India and to describe the cascade of care from
      HIV diagnosis to virological suppression after antiretroviral therapy (ART)
      initiation. Multivariable analysis was performed using competing risk regression.
      The cumulative incidence of attrition due to mortality or LTFU after five year of
      follow-up was 16% from entry into care to ART initiation and 24.9% after ART
      initiation. Of all children diagnosed with HIV, it was estimated that 91.9%
      entered into care, 77.2% were retained until ART initiation, 58% stayed in care
      after ART initiation, and 43.4% achieved virological suppression on ART.
      Approximately half of the attrition occurred before ART initiation, and the other
      half after starting ART. Belonging to socially disadvantaged communities and
      living >90 min from the hospital were associated with a higher risk of attrition.
      Being >10 years old and having higher 12-month risk of AIDS (calculated using the
      absolute CD4 lymphocyte count and the age) were associated with an increased risk
      of mortality. These findings indicate that we should consider placing more
      emphasis on promoting research and implementing interventions to improve the
      engagement of HIV infected children in pre-ART care. The results of this study
      can be used by HIV programmes to design interventions aimed at reducing the
      attrition across the continuum of care of HIV infected children in India. 

PMID- 24688881
TI  - Degree of adaptive response in urban tolerant birds shows influence of habitat-of
      origin.
AB  - Urban exploiters and adapters are often coalesced under a term of convenience as
      'urban tolerant'. This useful but simplistic characterisation masks a more
      nuanced interplay between and within assemblages of birds that are more or less
      well adapted to a range of urban habitats. I test the hypotheses that objectively
      defined urban exploiter and suburban adapter assemblages within the broad urban
      tolerant grouping in Melbourne vary in their responses within the larger group to
      predictor variables, and that the most explanatory predictor variables vary
      between the two assemblages. A paired, partitioned analysis of exploiter and
      adapter preferences for points along the urban-rural gradient was undertaken to
      decompose the overall trend into diagnosable parts for each assemblage. In a
      similar way to that in which time since establishment has been found to be
      related to high urban densities of some bird species and biogeographic origin
      predictive of urban adaptation extent, habitat origins of members of bird
      assemblages influence the degree to which they become urban tolerant. Bird
      species that objectively classify as urban tolerant will further classify as
      either exploiters or adapters according to the degree of openness of their
      habitats-of-origin. 

PMID- 24688880
TI  - Solution and crystal structures of a C-terminal fragment of the neuronal isoform
      of the polypyrimidine tract binding protein (nPTB).
AB  - The eukaryotic polypyrimidine tract binding protein (PTB) serves primarily as a
      regulator of alternative splicing of messenger RNA, but is also co-opted to other
      roles such as RNA localisation and translation initiation from internal ribosome
      entry sites. The neuronal paralogue of PTB (nPTB) is 75% identical in amino acid
      sequence with PTB. Although the two proteins have broadly similar RNA binding
      specificities and effects on RNA splicing, differential expression of PTB and
      nPTB can lead to the generation of alternatively spliced mRNAs. RNA binding by
      PTB and nPTB is mediated by four RNA recognition motifs (RRMs). We present here
      the crystal and solution structures of the C-terminal domain of nPTB (nPTB34)
      which contains RRMs 3 and 4. As expected the structures are similar to each other
      and to the solution structure of the equivalent fragment from PTB (PTB34). The
      result confirms that, as found for PTB, RRMs 3 and 4 of nPTB interact with one
      another to form a stable unit that presents the RNA-binding surfaces of the
      component RRMs on opposite sides that face away from each other. The major
      differences between PTB34 and nPTB34 arise from amino acid side chain
      substitutions on the exposed beta-sheet surfaces and adjoining loops of each RRM,
      which are likely to modulate interactions with RNA. 

PMID- 24688882
TI  - Evaluation of the effect of formalin fixation on skin specimens in dogs and cats.
AB  - Skin and subcutaneous tissues are the origin of most common neoplasms affecting
      dogs, accounting for approximately one third of all tumors encountered in the
      species. Surgical excision is frequently the best chance for a cure; determining
      factors influencing the success of excision are vital for surgical management of
      cases. This work examined the shrinkage of skin of various lengths from three
      sites in formalin for both dogs and cats. Tissues were measured on the animal
      (initial measurement), at the time of excision (post-removal), and after formalin
      fixation (post-fixation). While shrinkage after tissue removal was found in
      samples from the thorax, abdomen, and rear leg in dogs and from the rear leg in
      cats, no significant shrinkage due to formalin fixation was detected in any
      sample except for the thoracic samples from the dog. Therefore, when determining
      where to make incisions to effect a surgical cure, initial measurements should
      take into account tissue shrinkage effects. 

PMID- 24688883
TI  - Using a pacifier to decrease sudden infant death syndrome: an emergency
      department educational intervention.
AB  - Background. Pacifier use decreases the risk of sudden infant death syndrome
      (SIDS). An emergency department (ED) visit may provide an opportunistic
      'teachable moment' for parents. Objectives. To test the hypotheses (1) that
      caregivers were less familiar with the role of pacifiers in sudden infant death
      (SIDS) prevention than other recommendations, and (2) that an ED educational
      intervention would increase pacifier use in infants younger than six months, and
      (3) that otitis media would not occur more frequently in pacifier users. Methods.
      We did an intervention-group-only longitudinal study in a county hospital ED. We
      measured pacifier use infants and baseline knowledge of SIDs prevention
      recommendations in caregivers. We followed up three months later to determine
      pacifier use, and 12 months later to determine episodes of otitis media. Results.
      We analyzed data for 780 infants. Parents knew of advice against co-sleeping in
      469/780 (60%), smoking in 660/776 (85%), and prone sleeping in 613/780 (79%).
      Only 268/777 (35%) knew the recommendation to offer a pacifier at bedtime. At
      enrollment 449/780 (58%) did not use a pacifier. Of 210/338 infants aged less
      than 6 months followed up 41/112 (37%) non-users had started using a pacifier at
      bedtime (NNT 3). Over the same period, 37/98 (38%) users had discontinued their
      pacifier. Otitis media did not differ between users and non-users at 12 months.
      Conclusion. Caregiver knowledge of the role of pacifiers in SIDS prevention was
      less than for other recommendations. Our educational intervention appeared to
      increase pacifier use. Pacifier use was not associated with increased otitis
      media. 

PMID- 24688884
TI  - Urban park characteristics, genetic variation, and historical demography of white
      footed mouse (Peromyscus leucopus) populations in New York City.
AB  - Severe fragmentation is a typical fate of native remnant habitats in cities, and
      urban wildlife with limited dispersal ability are predicted to lose genetic
      variation in isolated urban patches. However, little information exists on the
      characteristics of urban green spaces required to conserve genetic variation. In
      this study, we examine whether isolation in New York City (NYC) parks results in
      genetic bottlenecks in white-footed mice (Peromyscus leucopus), and test the
      hypotheses that park size and time since isolation are associated with genetic
      variability using nonlinear regression and information-theoretic model selection.
      White-footed mice have previously been documented to exhibit male-biased
      dispersal, which may create disparities in genetic variation between males and
      females in urban parks. We use genotypes of 18 neutral microsatellite data and
      four different statistical tests to assess this prediction. Given that sex-biased
      dispersal may create disparities between population genetic patterns inferred
      from bi- vs. uni-parentally inherited markers, we also sequenced a 324 bp segment
      of the mitochondrial D-loop for independent inferences of historical demography
      in urban P. leucopus. We report that isolation in urban parks does not
      necessarily result in genetic bottlenecks; only three out of 14 populations in
      NYC parks exhibited a signature of a recent bottleneck at 18 neutral
      microsatellite loci. Mouse populations in larger urban parks, or parks that have
      been isolated for shorter periods of time, also do not generally contain greater
      genetic variation than populations in smaller parks. These results suggest that
      even small networks of green spaces may be sufficient to maintain the
      evolutionary potential of native species with certain characteristics. We also
      found that isolation in urban parks results in weak to nonexistent sex-biased
      dispersal in a species known to exhibit male-biased dispersal in less fragmented
      environments. In contrast to nuclear loci, mitochondrial D-loop haplotypes
      exhibited a mutational pattern of demographic expansion after a recent bottleneck
      or selective sweep. Estimates of the timing of this expansion suggest that it
      occurred concurrent with urbanization of NYC over the last few dozens to hundreds
      of years. Given the general non-neutrality of mtDNA in many systems and evidence
      of selection on related coding sequences in urban P. leucopus, we argue that the
      P. leucopus mitochondrial genome experienced recent negative selection against
      haplotypes not favored in isolated urban parks. In general, rapid adaptive
      evolution driven by urbanization, global climate change, and other human-caused
      factors is underappreciated by evolutionary biologists, but many more cases will
      likely be documented in the near future. 

PMID- 24688885
TI  - Religious attendance after elevated depressive symptoms: is selection bias at
      work?
AB  - In an attempt to determine if selection bias could be a reason that religious
      attendance and depression are related, the predictive value of elevated
      depressive symptoms for a decrease in future attendance at religious services was
      examined in a longitudinal panel of 1,673 Dutch adults. Religious attendance was
      assessed yearly over five years using the single question, "how often do you
      attend religious gatherings nowadays?" Depressive symptoms were assessed four
      times within the first year using the Depression subscale of the Brief Symptom
      Inventory. Logistic regression models of change in attendance were created,
      stratifying by baseline attendance status. Attenders who developed elevated
      symptoms were less likely to subsequently decrease their attendance (relative
      risk ratio: 0.55, 95% CI [0.38-0.79]) relative to baseline as compared to those
      without elevated symptoms. This inverse association remained significant after
      controlling for health and demographic covariates, and when using multiply
      imputed data to account for attrition. Non-attenders were unlikely to start
      attending after elevated depressive symptoms. This study provides counter
      evidence against previous findings that church attenders are a self-selected
      healthier group. 

PMID- 24688887
TI  - A changing landscape.

PMID- 24688888
TI  - Spotlights on our sister journals: ChemistryOpen 1/2014.
AB  - On these pages, we feature a selection of the excellent work that has recently
      been published in our sister journals. If you are reading these pages on a
      computer, click on any of the items to read the full article. Otherwise please
      see the DOIs for easy online access through Wiley Online Library. 

PMID- 24688886
TI  - Strategies for delivery of therapeutics into the central nervous system for
      treatment of lysosomal storage disorders.
AB  - Lysosomal storage disorders (LSDs) are a group of about fifty life-threatening
      conditions caused by genetic defects affecting lysosomal components. The
      underscoring molecular deficiency leads to widespread cellular dysfunction
      through most tissues in the body, including peripheral organs and the central
      nervous system (CNS). Efforts during the last few decades have rendered a
      remarkable advance regarding our knowledge, medical awareness, and early
      detection of these genetic defects, as well as development of several treatment
      modalities. Clinical and experimental strategies encompassing enzyme replacement,
      gene and cell therapies, substrate reduction, and chemical chaperones are showing
      considerable potential in attenuating the peripheral pathology. However, a major
      drawback has been encountered regarding the suboptimal impact of these approaches
      on the CNS pathology. Particular anatomical and biochemical constraints of this
      tissue pose a major obstacle to the delivery of therapeutics into the CNS.
      Approaches to overcome these obstacles include modalities of local
      administration, strategies to enhance the blood-CNS permeability, intranasal
      delivery, use of exosomes, and those exploiting targeting of transporters and
      transcytosis pathways in the endothelial lining. The later two approaches are
      being pursued at the time by coupling therapeutic agents to affinity moieties and
      drug delivery systems capable of targeting these natural transport routes. This
      approach is particularly promising, as using paths naturally active at this
      interface may render safe and effective delivery of LSD therapies into the CNS. 

PMID- 24688889
TI  - Diastereoselective additive trifluoromethylation/halogenation of isoxazole
      triflones: synthesis of all-carbon-functionalized trifluoromethyl isoxazoline
      triflones.
AB  - Highly functionalized 5-trifluoromethyl-2-isoxazoline derivatives featuring a
      triflyl (SO2CF3) group at the 4-position were successfully synthesized via
      diastereoselective trifluoromethylation and halogenation of isoxazole triflones
      using the Ruppert- Prakash reagent. The trifluoromethylation is quite general in
      terms of the substrates including 3,5-diaryl isoxazole triflones and 3-aryl-5
      styrylisoxazole triflones to provide products in high yields with excellent
      diastereoselectivities. The highly functionalized 5-trifluoromethyl-2-isoxazoline
      derivatives are expected to be a new class of antiparasiticides. Thus the triflyl
      group both activates isoxazoles and the 4-postion of CF3 adducts, and has a
      potential biological function. 

PMID- 24688890
TI  - One-pot synthesis and applications of N-heteroaryl iodonium salts.
AB  - An efficient one-pot synthesis of N-heteroaryl iodonium triflates from the
      corresponding N-heteroaryl iodide and arene has been developed. The reaction
      conditions resemble our previous one-pot syntheses, with suitable modifications
      to allow N-heteroaryl groups. The reaction time is only 30 min, and no anion
      exchange is required. The obtained iodonium salts were isolated in a protonated
      form, these salts can either be employed directly in applications or be
      deprotonated prior to use. The aryl groups were chosen to induce chemoselective
      transfer of the heteroaryl moiety to various nucleophiles. The reactivity and
      chemoselectivity of these iodonium salts were demonstrated by selectively
      introducing a pyridyl moiety onto both oxygen and carbon nucleophiles in good
      yields. 

PMID- 24688891
TI  - Difluoro-and Trifluoromethylation of Electron-Deficient Alkenes in an
      Electrochemical Microreactor.
AB  - Electrochemical microreactors, which have electrodes integrated into the flow
      path, can afford rapid and efficient electrochemical reactions without redox
      reagents due to the intrinsic properties of short diffusion distances. Taking
      advantage of electrochemical microreactors, Kolbe electrolysis of di-and
      trifluoroacetic acid in the presence of various electron-deficient alkenes was
      performed under constant current at continuous flow at room temperature. As a
      result, di-and trifluoromethylated compounds were effectively produced in either
      equal or higher yields than identical reactions under batch conditions previously
      reported by Uneyamas group. The strategy of using electrochemical microreactor
      technology is useful for an effective fluoromethylation of alkenes based on Kolbe
      electrolysis in significantly shortened reaction times. 

PMID- 24688892
TI  - Understanding E2 versus SN2 Competition under Acidic and Basic Conditions.
AB  - Our purpose is to understand the mechanism through which pH affects the
      competition between base-induced elimination and substitution. To this end, we
      have quantum chemically investigated the competition between elimination and
      substitution pathways in H2O+C2H5OH2 (+) and OH(-)+C2H5OH, that is, two related
      model systems that represent, in a generic manner, the same reaction under acidic
      and basic conditions, respectively. We find that substitution is favored in the
      acidic case while elimination prevails under basic conditions. Activation-strain
      analyses of the reaction profiles reveal that the switch in preferred reactivity
      from substitution to elimination, if one goes from acidic to basic catalysis, is
      related to (1) the higher basicity of the deprotonated base, and (2) the change
      in character of the substrates LUMO from C(beta)-H bonding in C2H5OH2 (+) to
      C(beta)-H antibonding in C2H5OH. 

PMID- 24688893
TI  - Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule
      cells.
AB  - NADPH oxidases are the major sources of reactive oxygen species in
      cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is
      present in humans but not rodents. Because Nox isoforms in renal proximal tubules
      (RPTs) are involved in the pathogenesis of hypertension, we tested the hypothesis
      that NOX5 is differentially expressed in RPT cells from normotensive (NT) and
      hypertensive subjects (HT). We found that NOX5 mRNA, total NOX5 protein, and
      apical membrane NOX5 protein were 4.2+/-0.7-fold, 5.2+/-0.7-fold, and 2.8+/-0.5
      fold greater in HT than NT. Basal total NADPH oxidase activity was 4.5+/-0.2-fold
      and basal NOX5 activity in NOX5 immunoprecipitates was 6.2+/-0.2-fold greater in
      HT than NT (P=<0.001, n=6-14/group). Ionomycin increased total NOX and NOX5
      activities in RPT cells from HT (P<0.01, n=4, ANOVA), effects that were abrogated
      by pre-treatment of the RPT cells with diphenylene-iodonium or superoxide
      dismutase. Silencing NOX5 using NOX5-siRNA decreased NADPH oxidase activity (
      45.1+/-3.2% vs. mock-siRNA, n=6-8) in HT. D1-like receptor stimulation decreased
      NADPH oxidase activity to a greater extent in NT (-32.5+/-1.8%) than HT (-14.8+/
      1.8). In contrast to the marked increase in expression and activity of NOX5 in
      HT, NOX1 mRNA and protein were minimally increased in HT, relative to NT; total
      NOX2 and NOX4 proteins were not different between HT and NT, while the increase
      in apical RPT cell membrane NOX1, NOX2, and NOX4 proteins in HT, relative to NT,
      was much less than those observed with NOX5. Thus, we demonstrate, for the first
      time, that NOX5 is expressed in human RPT cells and to greater extent than the
      other Nox isoforms in HT than NT. We suggest that the increased expression of
      NOX5, which may be responsible for the increased oxidative stress in RPT cells in
      human essential hypertension, is caused, in part, by a defective renal
      dopaminergic system. 

PMID- 24688894
TI  - N(6)-isopentenyladenosine and analogs activate the NRF2-mediated antioxidant
      response.
AB  - N(6)-isopentenyladenosine (i(6)A), a naturally occurring modified nucleoside,
      inhibits the proliferation of human tumor cell lines in vitro, but its mechanism
      of action remains unclear. Treatment of MCF7 human breast adenocarcinoma cells
      with i(6)A or with three synthetic analogs (allyl(6)A, benzyl(6)A, and butyl(6)A)
      inhibited growth and altered gene expression. About 60% of the genes that were
      differentially expressed in response to i(6)A treatment were also modulated by
      the analogs, and pathway enrichment analysis identified the NRF2-mediated
      oxidative stress response as being significantly modulated by all four compounds.
      Luciferase reporter gene assays in transfected MCF7 cells confirmed that i(6)A
      activates the transcription factor NRF2. Assays for cellular production of
      reactive oxygen species indicated that i(6)A and analogs had antioxidant effects,
      reducing basal levels and inhibiting the H2O2- or 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced production in MCF7 or dHL-60 (HL-60 cells induced to
      differentiate along the neutrophilic lineage) cell lines, respectively. In vivo,
      topical application of i(6)A or benzyl(6)A to mouse ears prior to TPA stimulation
      lessened the inflammatory response and significantly reduced the number of
      infiltrating neutrophils. These results suggest that i(6)A and analogs trigger a
      cellular response against oxidative stress and open the possibility of i(6)A and
      benzyl(6)A being used as topical anti-inflammatory drugs. 

PMID- 24688895
TI  - High throughput assay for evaluation of reactive carbonyl scavenging capacity.
AB  - Many carbonyl species from either lipid peroxidation or glycoxidation are
      extremely reactive and can disrupt the function of proteins and enzymes. 4
      hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived
      reactive carbonyl species. The presence of these toxics leads to carbonyl stress
      and cause a significant amount of macromolecular damages in several diseases.
      Much evidence indicates trapping of reactive carbonyl intermediates may be a
      useful strategy for inhibiting or decreasing carbonyl stress-associated
      pathologies. There is no rapid and convenient analytical method available for the
      assessment of direct carbonyl scavenging capacity, and a very limited number of
      carbonyl scavengers have been identified to date, their therapeutic potential
      being highlighted only recently. In this context, we have developed a new and
      rapid sensitive fluorimetric method for the assessment of reactive carbonyl
      scavengers without involvement glycoxidation systems. Efficacy of various thiol-
      and non-thiol-carbonyl scavenger pharmacophores was tested both using this
      screening assay adapted to 96-well microplates and in cultured cells. The
      scavenging effects on the formation of Advanced Glycation End-product of Bovine
      Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as
      molecular models were also examined. Low molecular mass thiols with an alpha
      amino-beta-mercaptoethane structure showed the highest degree of inhibitory
      activity toward both alpha,beta-unsaturated aldehydes and dicarbonyls. Cysteine
      and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065
      which is currently approved for clinical use as a protective agent against
      radiation and renal toxicity was identified as the best inhibitor of 4
      hydroxynonenal. 

PMID- 24688897
TI  - Effectiveness of Anabolic Steroid Preventative Intervention among Gym Users:
      Applying Theory of Planned Behavior.
AB  - BACKGROUND: Use of anabolic androgenic steroids (AAS) has been associated with
      adverse physical and psychiatric effects and it is known as rising problem among
      youth people. This study was conducted to evaluate anabolic steroids preventative
      intervention efficiency among gym users in Iran and theory of planned behaviour
      was applied as theoretical framework. METHODS: Overall, 120 male gym users
      participated in this study as intervention and control group. This was a
      longitudinal randomized pretest - posttest series control group design panel
      study to implement a behaviour modification based intervention to prevent AAS
      use. Cross -tabulation and t-test by using SPSS statistical package, version 13
      was used for the statistical analysis. RESULTS: It was found significant
      improvements in average response for knowledge about side effects of AAS
      (P<0.001), attitude toward, and intention not to use AAS. Additionally after
      intervention, the rate of AAS and supplements use was decreased among
      intervention group. CONCLUSION: Comprehensive implementation against AAS abuse
      among gym users and ado-lescences would be effective to improve adolescents'
      healthy behaviors and intend them not to use AAS.

PMID- 24688896
TI  - Advantages and Disadvantages of Health Care Accreditation Mod-els.
AB  - BACKGROUND: This systematic review seeks to define the general advantages and
      disadvan-tages of accreditation programs to assist in choosing the most
      appropriate approach. METHOD: Systematic search of SID, Ovid Medline & PubMed
      databases was conducted by the keywords of accreditation, hospital, medical
      practice, clinic, accreditation models, health care and Persian meanings. From
      2379 initial articles, 83 articles met the full inclusion criteria. From initial
      analysis, 23 attributes were identified which appeared to define advantages and
      disadvantages of different accreditation approaches and the available systems
      were compared on these. RESULTS: Six systems were identified in the international
      literature including the JCAHO from USA, the Canadian program of CCHSA, and the
      accreditation programs of UK, Australia, New Zealand and France. The main
      distinguishing attributes among them were: quality improve-ment, patient and
      staff safety, improving health services integration, public's confi-dence,
      effectiveness and efficiency of health services, innovation, influence global
      standards, information management, breadth of activity, history, effective
      relationship with stakeholders, agreement with AGIL attributes and independence
      from government. CONCLUSION: Based on 23 attributes of comprehensive
      accreditation systems we have defined from a systematic review, the JCAHO
      accreditation program of USA and then CCHSA of Can-ada offered the most
      comprehensive systems with the least disadvantages. Other programs such as the
      ACHS of Australia, ANAES of France, QHNZ of New Zealand and UK accredita-tion
      programs were fairly comparable according to these criteria. However the decision
      for any country or health system should be based on an assessment weighing up
      their specific objec-tives and needs.

PMID- 24688898
TI  - Disordered Eating Attitudes and Their Correlates among Iranian High School Girls.
AB  - BACKGROUND: Disordered eating attitudes are contributing factors to the
      development of eating disorders. Adolescent girls are at high risk for eating
      diseases. In Iran, there is few data on the subject, especially in Azarian
      adolescent girls, so we did this study for assessing disordered eating attitudes
      and their correlates among Iranian Azarbaijani high school girls. METHODS: In a
      cross-sectional study, 1887 high school girls were selected. Eating Attitude Test
      26 (EAT-26) and socio economical questionnaires were used. The EAT-26 score of 20
      or higher defined as disordered eating attitudes. Data were analyzed using the
      Statistical Program for Social Sciences, by using from descriptive and analytical
      statistics. RESULTS: Reliability and validity of the translated EAT-26 were 0.80,
      0.76, respectively. In studied subjects, mean (SD) of EAT-26 was 11.71(8.48).
      Totally, 16.7% (C.I with 95%: 15.1- 18.3%) of students had disordered eating
      attitudes. About half of the participants were unhappy with their body weight and
      considered themselves as obese. Mean of EAT-26 was higher in this group. Groups,
      who intent to weight loss, were smoker, and who had age of menarche less than 11
      years, also had higher EAT-26 scores. Parent's literacy or job, birth order,
      family size or income and house ownership had not any significant effect on EAT
      26 score. CONCLUSIONS: Persian version of EAT-26 has good reliability and
      validity for assessing disordered eating attitudes in Azarian girl adolescents.
      Prevalence of disordered eating attitudes among Azarian adolescent girls are in
      the range of some studies, but are less than Arabian countries, and some European
      ones. In adolescent girls, body weight dissatisfaction, smoking and early
      menarche has important role in eating attitudes.

PMID- 24688899
TI  - Incidence of leukemia in the northwest of iran.
AB  - BACKGROUND: Leukemia is cancer of the blood or bone marrow, characterized by an
      unusual increase in white blood cells. It is the sixth most common malignancy in
      the country in both males and females. The aim of this study was to document some
      epidemiological features of leukemia in the Northwest of Iran. METHODS: The study
      subjects (n=669, including 377 males and 292 females) comprised all leukemia
      cases registered/notified to the clinical and pathology centers of Tabriz and
      Ardebil cities, from 2003 to 2006. All patients were classified using the ICD-10
      based coding system (C91-C95, C77 and C42). Ninety-five percent confidence
      intervals were calculated to assess the statistical significance of the data.
      RESULTS: Annual incidence of leukemia was 3.7 [95% CI: 3.3-4.0] and 4.9 [95% CI:
      4.2-5.6] per 100 000 population in Tabriz and Ardebil, respectively, with an
      overall case fatality rate of 13.5 percent [95% CI: 10.8-16.0]. The sex ratio
      (male/female) was 1.23. Myeloid leukemia (C92) and Hematopoetic and
      Reticuloendothelial system (C42) accounted proportionally for more than 47
      percent of cases in the region. Over the study period, the annual occurrence of
      leukemia in the region increased from 3.9 [95% CI: 3.4-4.5] to 4.1 [95% CI: 3.5
      4.6] per 100 000 population (P>0.1). CONCLUSIONS: The data from this cross
      sectional study of leukemia in the North-West of Iran may be used as the baseline
      information to establish a population-based registry of hema-tologic disorders in
      the area for health care and research purposes. However, more investiga-tions are
      needed to develop effective strategies to control the relevant disorders in high
      risk groups.

PMID- 24688900
TI  - Fluids Intake and Beverage Consumption Pattern among University Students.
AB  - BACKGROUND: Insufficient and inappropriate daily fluid intake in a long period
      may have adverse effect on human's health. Therefore, the present study evaluated
      the amounts and sources of fluids consumed by university students to determine
      whether these amounts and sources of fluid were enough and appropriate. METHODS:
      In this descriptive study, 245 (142 females and 103 males) volunteer students of
      Tabriz University of Medical Sciences in 2009 were recruited. Food and fluid
      intake of subjects were as-sessed by 24-hour recall method of 3 days (two week
      days and one week- end included). Dietary intake of subjects was analyzed by
      Nutritionist III software program. The mean total fluid intake (drinking fluid
      values merged with data on the water content of foods) and the rate of metabolic
      water were figured out. Comparisons of the results with recommended dietary
      values were made using student's t-test.. Data of dietary intakes for two under
      reporter female subjects were not included in the statistical analysis. RESULTS:
      Daily total mean of fluid intake for girls (1598+/-40ml) and boys (1861+/-59ml)
      reflect the sum of beverages (Girls, 818+/-29ml; boys, 1147+/-57ml) and food
      water (Girls, 780+/-47ml; boys, 714+/-86m). The most consumed beverage for girls
      and boys were water (40%) and tea (49%) respectively. Daily mean intake of milk
      for girls and boys were 106.31+/-10ml (13%) and 57.30+/-11ml (5%), respectively.
      CONCLUSION: The mean daily fluid intake of subjects, specially water, and milk
      was lower than rec-ommended values. Therefore, there is an urgent need for
      tailored nutrition intervention targeting the young adults to improve their
      beverage choices.

PMID- 24688901
TI  - Effects of abandoned arsenic mine on water resources pollution in north west of
      iran.
AB  - BACKGROUND: Pollution due to mining activities could have an important role in
      health and welfare of people who are living in mining area. When mining operation
      finishes, environ-ment of mining area can be influenced by related pollution e.g.
      heavy metals emission to wa-ter resources. The present study was aimed to
      evaluate Valiloo abandoned arsenic mine ef-fects on drinking water resources
      quality and possible health effects on the residents of min-ing area in the North
      West of Iran. METHODS: Water samples and some limited composite wheat samples in
      downstream of min-ing area were collected. Water samples were analyzed for
      chemical parameters according to standard methods. For determination of arsenic
      in water samples, Graphite Furnace Atomic Absorption Spectrometric Method (GFAAS)
      and for wheat samples X - Ray Fluorescence (XRF) and Inductively Coupled Plasma
      Method (ICP) were used. Information about possible health effects due to exposure
      to arsenic was collected through interviews in studied villages and health center
      of Herris City. RESULTS: The highest concentrations of arsenic were measured near
      the mine (as high as 2000 ug/L in Valiloo mine opening water). With increasing
      distance from the mine, concentration was decreased. Arsenic was not detectable
      in any of wheat samples. Fortunately, no health effects had been reported between
      residents of studied area due to exposure to arsenic. CONCLUSION: Valiloo
      abandoned arsenic mine has caused release of arsenic to the around en-vironment
      of the mine, so arsenic concentration has been increased in the groundwater and
      also downstream river that requires proper measures to mitigate spread of
      arsenic.

PMID- 24688902
TI  - Physical Activity and Stages of Change among College Students.
AB  - BACKGROUND: To investigate of physical activity distribution bases on stages of
      change among Isfahan University of Medical Sciences central part of Iran.
      METHODS: Exercise behavior stages of change construct questionnaire were
      collected from 504 participants by using a convenience sample in May 2010.
      RESULTS: 73.8% of subjects were in earlier stages of exercise behavior
      (Precontemplation, contemplation, and preparation stages) and tended to be
      inactive. The exercise behavior was not influenced by age, education levels, and
      marital status. CONCLUSION: The majority of the university students are suffering
      physical inactivity that need to design more effective physical activity
      promotion programs in the community and univer-sities level.

PMID- 24688903
TI  - School Bag Weight and the Occurrence of Shoulder, Hand/Wrist and Low Back
      Symptoms among Iranian Elementary Schoolchildren.
AB  - BACKGROUND: Schoolchildren usually use school bags to carry their school
      materials. Carry-ing heavy school bags can cause several problems such as
      musculoskeletal problems among schoolchildren. The aim of this study was to
      investigate the association between the weight of school bags and the occurrence
      of low back, shoulder and hand/wrist symptoms among pri-mary school children.
      METHOD: This cross-sectional, descriptive-analytical study was conducted among a
      sample of 307 elementary school children in Tabriz, Iran. Data were collected
      using a questionnaire and from measurement of the school bag weight, body weight
      and height of each participant. Data were analysed using SPSS software. RESULTS:
      The average load carried by schoolchildren was 2.9 kg, representing approximately
      10% of the children's body weight. Girls and lower grade children carried a
      greater percent-age of their body weights. Approximately 86% of the children
      reported some kind of muscu-loskeletal symptoms. The occurrence of shoulder,
      wrists/hands, and low back pain among school-children was 70%, 18.5% and 8.7%,
      respectively. The results of binary logistic regres-sion indicated that the
      school bag weight (expressed as a percentage of body weight) was only
      significantly associated with hand/wrist symptoms (P<0.05). Girls were more
      likely to com-plaint from low back pain than boys were. Age was significantly
      negatively associated with hand/wrist symptoms. Body mass index was also
      significantly associated with shoulder symptoms. CONCLUSION: The results indicate
      a high prevalence of musculoskeletal symptoms among elemen-tary schoolchildren.
      Preventive measures and appropriate guidelines with regard to safe load carriage
      in schoolchildren are therefore needed to protect this age group.

PMID- 24688904
TI  - Approaches to Recruiting 'Hard-To-Reach' Populations into Re-search: A Review of
      the Literature.
AB  - BACKGROUND: 'Hard-to-reach' is a term used to describe those sub-groups of the
      population that may be difficult to reach or involve in research or public health
      programmes. Application of a single term to call these sub-sections of
      populations implies a homogeneity within distinct groups, which does not
      necessarily exist. Different sampling techniques were introduced so far to
      recruit hard-to-reach populations. In this article, we have reviewed a range of
      ap-proaches that have been used to widen participation in studies. METHODS: We
      performed a Pubmed and Google search for relevant English language articles using
      the keywords and phrases: (hard-to-reach AND population* OR sampl*), (hidden AND
      population* OR sample*) and ("hard to reach" AND population* OR sample*) and a
      consul-tation of the retrieved articles' bibliographies to extract empirical
      evidence from publications that discussed or examined the use of sampling
      techniques to recruit hidden or hard-to-reach populations in health studies.
      RESULTS: Reviewing the literature has identified a range of techniques to recruit
      hard-to-reach populations, including snowball sampling, respondent-driven
      sampling (RDS), indigenous field worker sampling (IFWS), facility-based sampling
      (FBS), targeted sampling (TS), time-location (space) sampling (TLS), conventional
      cluster sampling (CCS) and capture re-capture sampling (CR). CONCLUSION: The
      degree of compliance with a study by a certain 'hard-to-reach' group de-pends on
      the characteristics of that group, recruitment technique used and the subject of
      inter-est. Irrespective of potential advantages or limitations of the recruitment
      techniques reviewed, their successful use depends mainly upon our knowledge about
      specific characteristics of the target populations. Thus in line with attempts to
      expand the current boundaries of our know-ledge about recruitment techniques in
      health studies and their applications in varying situa-tions, we should also
      focus on possibly all contributing factors which may have an impact on
      participation rate within a defined population group.

PMID- 24688905
TI  - Psychometric Properties of the Iranian Version of the Behavioral Regulation in
      Exercise Questionnaire-2 (BREQ-2).
AB  - BACKGROUND: The Behavioral Regulation in Exercise Questionnaire (BREQ) and the
      BREQ-2 are the most commonly used measures of behavioural regulation in exercise
      psychology. The purpose of the study was to assess the validity and reliability
      of the Iranian version of the BREQ-2 on a sample of university students. METHODS:
      The BREQ-2 was translated into Persian by qualified experts and the psychometric
      properties of the instrument were assessed. Content validity was established,
      using a panel of 12 Iranian experts in the areas of health education, psychology,
      and exercise. Construct validity was assessed via confirmatory factor analysis
      (CFA), using LISREL 8.80 (N = 418). The reliability of the BREQ-2 was assessed,
      using a 2-week test-retest to establish its stability and Cronbach's Alpha to
      estimate its internal consistency. RESULTS: The Iranian version of the BREQ-2 was
      slightly modified to improve content validity. Primary results of confirmatory
      factor analysis did not fully support the 5-factor uncorrelated model. The model
      was modified; and the fit indices indicated that the 5-factor correlated model
      was the best fit. The scale was found to have acceptable internal consistency
      (alpha > 0.7) and test-retest reliability (intra-class correlation coefficient
      [ICC] > 0.80). CONCLUSION: The Iranian BREQ-2 has acceptable validity and
      reliability in the study sample and may be used in relevant studies to assess
      behavioural regulation in similar samples.

PMID- 24688906
TI  - Socioeconomic status and coronary heart disease.
AB  - BACKGROUND: Iran has undergone a remarkable demographic transition over the last
      three decades. Socioeconomic status (SES) indicators including education, income,
      and occupation are associated with coronary heart disease (CHD) risk factors,
      morbidity, and mortality. The aim of the present study was to describe
      demographic and socioeconomic characteristics, their association to the diseases,
      and to explore the predictive risk of CHD in Tabriz, the fourth largest city in
      Iran and the capital of East Azerbaijan Province. METHODS: This cross-sectional
      descriptive study was carried out to explore and analyze the current SES status
      of CHD patients. The study was conducted in Tabriz and all patients (n=189)
      refereed to the Central Referral Hospital for cardiac patients (Shahid Madani
      Hospi-tal) from 2009 to 2010 were considered. A researcher structured
      questionnaire with 15 ques-tions was used to collect data. Descriptive statistics
      were used to describe the basic SES fea-tures of the CHD patients and data
      analysis was done using SPSS ver. 16. RESULTS: Less educated participants were
      more susceptible to CHD. Regarding to occupa-tional status, housewives and
      retired men were in higher risk of CHD than the rest of the peo-ple.  Studied
      patients also reported to be mostly from urban areas that were living in apart
      ment complexes. CONCLUSION: In line with some international research evidence the
      study results suggested that people from lower/middle social classes were in
      greater CHD risk than higher social classes.  This epidemic might be halted
      through the promotion of healthier lifestyles and the support of environmental
      and policy changes.

PMID- 24688907
TI  - Food habits related to osteoporosis in women in iran.
AB  - BACKGROUND: Osteoporosis is an important public health problem. The aim of this
      study was to investigate food habits and some factors related to osteoporosis in
      women in Iran. METHODS: This cross-sectional study was conducted on 399
      childbearing age women who were attending health centers and 200 healthcare
      providers in 2007. Food habits and dietary calcium intake was evaluated by food
      frequency questionnaire and 24-hour recall method. Weight and height of subjects
      were also measured. Independent t-test, Mann-withney U test, Pearson, Spearman
      and Partial correlation coefficient tests were used for analyzing of data.
      RESULTS: Two groups of women had calcium intake deficiency. Daily frequency of
      milk, cheese, fruit and coffee consumptions in healthcare providers (0.82+/-0.82,
      0.94+/-0.49, 2.01+/-1.28 and 0.84+/-2.05, P<0.02)  were significantly higher than
      those of women attending health centers(0.58+/-0.72, 0.84+/-0.32, 1.50+/-0.99 and
      0.48+/-1.25).  Mean frequency use of dark vegetables, cola and pickles were
      significantly (P<0.004) higher in women who attending health centers (0.67+/
      0.50, 1.55+/-2.36 and 1.92+/-2.03) than those of the other group (0.50+/-0.44,
      1.09+/-2.65 and 1.49+/-1.72). In women who were attending health centers,
      negative and posi-tive significant relationship was found between daily calcium
      intake with age (P<0.04) and educational level (P<0.001). No significant
      relationship was found between body mass index with studied variables.
      CONCLUSION: Women of health care providers had healthier food habits compared to
      women who attending health centers. Educational programs are suggested to improve
      food habits among women to prevent osteoporosis in later life.

PMID- 24688908
TI  - Development of a Rheumatoid Arthritis Education Program using the PRECEDE_PROCEED
      Model.
AB  - BACKGROUND: In order to help rheumatoid arthritis (RA) patients in carrying out
      and at-taining relevant self-care behaviors and adaptation to the physical
      limitations of this dis-ease and, conse-quently, promoting their level of health
      status, an education program based on the PRECEDE component of the PRECEDE
      PROCEED model targeting patients with RA was developed. This paper describes the
      planning of a RA Patient Education Program (RAPEP) designed to promote their
      quality of life. METHODS: The development of the program began with a
      comprehensive review of the li-terature. This included a review of the signs and
      symptoms of RA, accompanying func-tional disabilities, previous educational
      programs and the effect of the disease on the pa-tient's quality of life. Be
      sides, in order to help inform RAPEP program development, and organize the survey
      according to the factors identified in the PRECEDE model a cross-sectional survey
      was applied on a non-prob-ability sample of 181 outpatients in Yazd, center of
      Iran. RESULTS: The quality of life (QOL) problem identified was the considerable
      low role func-tioning, health perception and physical functioning due to chronic
      pain. One of the most significant modi-fiable behavioral factors impacting pain
      and functional limitations was self-care behaviors in RA patients. Higher level
      of knowledge, attitude, self-efficacy, enabling factors and social support is
      associated with better self-care behavior. CONCLUSIONS: The PRECEDE component of
      the PRECEDE-PROCEED model provided a com-prehensive conceptual framework for the
      development of RAPEP aiming at RA pa-tients in Yazd. Further research to evaluate
      this educational program is suggested.

PMID- 24688909
TI  - Aberrant Behaviors and Road Accidents among Iranian Truck Drivers, 2010.
AB  - BACKGROUND: Road accidents are a social phenomenon in different communities that
      its infra-structural dimensions of which as well as technologic failures such as
      road quality, and tech-nical faults of automobiles, need to be assessed in
      detail. Iran has the first order in the world for deadly road accidents. This
      study was designed to assess the association between aberrant behaviors of truck
      drivers and the incidence of road accidents in Yazd, center of Iran, in 2010.
      METHODS: This cross-sectional descriptive-analytic study was conducted on 300
      truck drivers in Yazd. We used 3 questionnaires, including one for demographic
      data, Driver Behavior Questionnaire (DBQ), and one for drivers' self-evaluation
      of the of their driving. RESULTS: Five types of the behavior had the highest
      frequency: Misjudge speed of oncoming vehicle when overtaking.; Deliberately
      disregard the speed limits late at night or very early in the morning.; Ignore
      'give way' signs, and narrowly avoid colliding with traffic having right of way.;
      Stuck behind a slow-moving vehicle on a two-lane highway, you are driven by
      frustration to try to overtake in risky circumstances.; Drive with only 'half-an
      eye' on the road while looking at a map, changing a cassette or radio channel,
      etc. The more the driver's driv-ing was influenced by emotional and mental states
      the more deliberate violations and slips. CONCLUSION: Among truck drivers, safety
      has not developed sufficiently, and because of the dangers of road accidents both
      for the drivers and other people and its economic losses, the importance of the
      presenting some solutions is completely obvious.

PMID- 24688910
TI  - Maternal body mass index, dietary intake and socioeconomic status: differential
      effects on breast milk zinc, copper and iron content.
AB  - BACKGROUND: As breast milk micronutrients content are essential for health and
      growth of the infants, this study was conducted to determine the breast milk
      zinc, copper and iron concen-trations and their possible correlations with
      maternal nutritional status, dietary intakes as well as socioeconomic status.
      METHODS: Breast milk samples and information on maternal anthropometric
      characteristics and dietary intake were collected from 90 Iranian lactating women
      with 3 different socioeco-nomic status who exclusively breastfed their infants.
      Concentrations of trace elements were analyzed using atomic absorption
      spectrophotometry. Nutritionist III program, Multiple Re-gression and ANOVA test
      were used for data analyses. RESULTS: The mean milk zinc, copper, and iron
      concentrations were 1.93 +/- 0.71, 0.58 +/- 0.32, and 0.81 +/- 0.2 mg/l,
      respectively. In all three SES groups only zinc mean level was lower than the
      recommended range. A significant difference was observed in breast milk zinc,
      copper and iron concentration between high and low SES groups (Zn (P<0.001), Cu
      (P<0.001) and Fe (P<0.044)) and also moderate and low SES groups (Zn (P<0.03), Cu
      (P<0.001) and Fe (P<0.049)). After adjusting for maternal body mass index (BMI),
      socioeconomic status, mean dietary energy, zinc, copper, and iron intakes, there
      was a negative and significant association between maternal age and breast milk
      zinc (beta=-0.28, P<0.034), copper (beta=-0.18, P<0.048), and iron (beta=-0.22,
      P<0.04) concentrations. CONCLUSION: In low socioeconomic group with lower mean
      age, breast milk mineral levels were higher than others and there was no
      significant correlation between mineral levels and dietary intake. Hence it is
      supposed that maternal age may be better predictor of breast milk mineral levels.

PMID- 24688911
TI  - Lifestyle Modification through Dietary Intervention: Health Promotion of Patients
      with Non-Alcoholic Fatty Liver Disease.
AB  - BACKGROUND: Prevalence of non-alcoholic fatty liver disease (NAFLD) is more
      common worldwide and no certain treatment apart from lifestyle modification has
      been established yet. Available data consistently show that energy intake is
      significantly higher in patients with NAFLD than in individuals with no evidence
      of fatty liver. Changing nutritional behaviors seems to be the primary approach
      for treatment, simultaneously addressing all the clinical and biochemical
      defects. This study was aimed to examine the effects of two different composition
      of low energy diet (diet I vs. diet II) on non-alcoholic fatty liver disease
      patients. METHODS: In this double-blind randomized controlled trial, 44
      ultrasonography-proven overweight non-alcoholic fatty liver disease patients were
      divided into two groups and received two low-energy diets (-500 kcal less than
      energy requirement individually) inc. diet I (Carbohydrate: Fat: Protein:
      55:25:20) and diet II (Carbohydrate: Fat: Protein: 40:40:20) for six weeks.
      Anthropometric and biochemical measures as well as liver enzymes were assessed
      after 12 hours fasting. RESULTS: After diet I and diet II, weight decreased
      significantly (%1.82 and %2.45, respectively). Liver enzymes and echogenicity
      decreased significantly by both diet I and diet II. Mean of triglyceride
      concentration decreased (%18.09) after diet II (P=0.023), while there was no
      significant change after diet I. Significant correlations were found between
      changes in aspartate aminotransferase with triglyceride and LDL-C diet I.
      CONCLUSION: Low energy diets can decrease liver enzymes regardless of their
      composition, while diet II seems to be more effective than diet I in reduction of
      weight and triglyceride level.

PMID- 24688912
TI  - Older People's Quality of Life and Role of Home-Based Technology.
AB  - BACKGROUND: Household devices may have a positive impact on daily lives by
      reducing the burden of several tasks and enriching social interaction. There are
      varieties of assistive devices such as alarms, sensors, detectors, and life style
      monitoring devices, which can help in compensating for the activity limitations
      caused by impairments. This study aimed to review the contribution that
      residential technology devices can make to older people's lives. METHODS: An open
      ended literature review following the guidance of the Centre for Review and
      Dissemination was conducted to establish the current understanding of the topics
      by using clear and appropriate criteria to select or reject studies. The studies
      entered into the review were limited by language, topic, and date of publication.
      RESULTS: The research literature indicated that residential facilities which
      appropriately are designed and supplied can have many benefits for older people
      such as increasing in-dependence, maximising physical and mental health, and
      improving their quality of life. CONCLUSION: Although most of the literature has
      explored the positive effects of technology devices on older adults' social
      networks, independence, psychological well-being, and social status, the
      possibilities of negative consequences have been neglected. KEYWORDS: Quality of
      life, Older people, Residential technology, Computer-mediated communication.

PMID- 24688913
TI  - No Child or Mother Left Behind; Implications for the US from Cuba's Maternity
      Homes.
AB  - BACKGROUND: Cuba, a "resource-poor" country, provides high-quality, free maternal
      care despite relatively low per capita health expenditures in comparison to
      similar expenditures in "resource rich" nations such as Canada and the US. This
      paper assesses maternal and child healthcare in Cuba, details the system of
      community-based regional maternity homes, and outlines specific recommendations
      for the US. METHODS: Based on observations during a visit to Cuba, and
      supplemental research on international health expenditures and health indicators
      such as infant and maternal mortality, this paper details maternal and child
      health in Cuba. RESULTS: Cuba utilizes community-based regional maternity homes
      to provide comprehensive care for women with high-risk pregnancies. This
      effective strategy of investing in maternal health by safeguarding pregnancies
      has lowered infant and maternal mortality rates significantly. Cuba has achieved
      neonatal, infant and under-five mortality rates that are better than or on par
      with resource rich nations such as the US. Additionally, within the Latin
      American and Caribbean region, Cuba has a low rate of maternal mortality.
      CONCLUSION: Positioning maternal and child health priorities to the policy
      foreground were a critical step in saving the lives of Cuban women and children.
      The US may benefit from Cuba's example with respect to maternal and child health.
      Cuba's model provides important health; rights and policy lessons for all nations
      are they resource rich or poor.

PMID- 24688914
TI  - Case-control study of dietary pattern and other risk factors for gastric cancer.
AB  - BACKGROUND: The rates of gastric cancer reported from Ardabil Province of Iran,
      are among the highest in the world. The aim of this study was to investigate the
      risk factors for gastric cancer in Ardabil Province. METHODS: This case-control
      study was conducted on 128 adults with mean age of 56.5 +/- 12.8 yr old in
      Ardebil City, Iran in 2010 - 2011. Forty-two people with gastric cancer and 86
      healthy people were recruited. Participants were interviewed using a structured
      questionnaire. Fasting blood samples were taken for measurement of IgG and IgA
      indices against Helicobacter pylori infection. Data were analyzed using the Chi
      square and Independent sample t-test.  RESULTS: Diet and H. pylori infection
      indices had the significant relationship with gastric cancer (P<0.05). Among
      dietary patterns, drinking hot tea, low intake of fresh vegetables and fruits,
      and unsaturated fat were the most significant risk factors (P<0.05). In gastric
      cancer patients, the levels of serum IgG and IgA as indicator of H. pylori
      infection were significantly (P<0.05) higher than the healthy subjects (IgG 37.7
      +/- 29.3 vs. 16.9 +/- 11.1 U/ml and IgA 50.5 +/- 44.7 vs. 22.9 +/- 15.8 U/ml). No
      significant relationship was observed between tobacco smoking and alcohol
      consumption with gastric cancer. CONCLUSION: Dietary pattern especially drinking
      hot tea and low consumption of unsaturated fat, fresh vegetables, and fruits, as
      well as H. pylori infection were the most important risk factors in gastric
      cancer patients.

PMID- 24688915
TI  - Public and private hospital services reform using data envelopment analysis to
      measure technical, scale, allocative, and cost efficiencies.
AB  - BACKGROUND: The aim of this study was to suggest a suitable context to develop
      efficient hospital systems while maintaining the quality of care at minimum
      expenditures. METHODS: This research aimed to present a model of efficiency for
      selected public and private hospitals of East Azerbaijani Province of Iran by
      making use of Data Envelopment Analysis approach in order to recognize and
      suggest the best practice standards. RESULTS: Among the six inefficient
      hospitals, 2 (33%) had a technical efficiency score of less than 50% (both
      private), 2 (33%) between 51 and 74% (one private and one public) and the rest
      (2, 33%) between 75 and 99% (one private and one public). CONCLUSION: In general,
      the public hospitals are relatively more efficient than private ones; it is
      recommended for inefficient hospitals to make use of the followings:
      transferring, selling, or renting idle/unused beds; transferring excess doctors
      and nurses to the efficient hospitals or other health centers; pensioning off,
      early retirement clinic officers, technicians/technologists, and other technical
      staff. The saving obtained from the above approaches could be used to improve
      remuneration for remaining staff and quality of health care services of
      hospitals, rural and urban health centers, support communities to start or
      sustain systematic risk and resource pooling and cost sharing mechanisms for
      protecting beneficiaries against unexpected health care costs, compensate the
      capital depreciation, increasing investments, and improve diseases prevention
      services and facilities in the provincial level.

PMID- 24688916
TI  - Effect of inulin and stevia on some physical properties of chocolate milk.
AB  - BACKGROUND: The aim of this study was to assess physical properties of dietetic
      chocolate milk produced by stevia as a sugar replacer and inulin. Along with
      having prebiotic effect, inulin can also participate in enhancing textural
      properties of beverages. Therefore, this novel food will be useful for all people
      especially for diabetics. METHODS: This study was carried out in Quality Control
      Laboratory of Food Science and Technology Department, Health and Nutrition
      Faculty, Tabriz University of Medical Science, during 2011-2012. The assay was
      performed on nine treatments with three replications. Sugar was substituted with
      stevia in two proportions of sucrose to stevia; 50:50 and 0:100. Inulin, in four
      levels of 0%, 2%, 4% and 6%, was added to the treatments of 50% and 100% stevia.
      The control sample contained no stevia and no inulin, such as commercial ones.
      Precipitation amount and viscosity were measured 24 hours after production. Data
      analyzed by one-way ANOVA, at the significant level of 0.05, using SPSS software
      ver. 17. RESULTS: Sugar replacement with stevia caused significant increase in
      precipitation and significant decrease in viscosity (P<0.05), whereas using
      inulin in formulation significantly decreased precipitation and increased
      viscosity (P<0.05). The sample containing 100% stevia and 6% inulin revealed a
      viscosity with a non-significant difference with the control (P>0.05). The sample
      containing 50% stevia and 6% inulin had the lowest precipitation while having a
      non-significantly difference with the control. Conclusion A thickener agent, such
      as inulin, should be used in the chocolate milk sweetened by stevia to improve
      physical properties of the product.

PMID- 24688917
TI  - Reporting of health promotion research: addressing the quality gaps in iran.
AB  - Quality of health behavior research determines usefulness of the findings for
      application. The authors individually scrutinized quality of a representative
      sample of abstracts (n=315) submitted to the 1st International and 4th National
      Congress on Health Education and Promotion, held in Tabriz, Iran on 16-19 May,
      2011. Among the assessed abstracts, introduction section had the standard format
      in 18.1% (CI: 14.2-22.7%), sampling method and sample size were concurrently
      explained in 56.3% (CI: 50.3-62.1%), and the data in 40.6% (CI: 35.4-46.1%) were
      insufficient to support the conclusion section. The observed heterogeneity in the
      quality of Iranian research may reflect gaps in research methodology education.
      Revision in the current research performance is recommended to ensure a more
      stringent national research output. 

PMID- 24688918
TI  - Honey and apoptosis in human gastric mucosa.
AB  - BACKGROUND: Gastric cancer is the fourth most common malignancy in the world.
      Honey is a complex mixture of special biological active constituents. Honey
      possesses antioxidant and antitumor properties. Nutritional studies have
      indicated that consumption of honey modulates the risk of developing gastric
      cancer. On the other hand, apoptosis has been reported to play a decisive role in
      precancerous changes. Our chief study was conducted to assess the relationship
      between consumption of honey and apoptosis in human gastric mucosa. METHOD: This
      cross-sectional study was conducted on 98 subjects over 18 years old, referred to
      two hospitals in Tabriz, Iran. Subjects were undergone an upper gastrointestinal
      endoscopy, 62 subjects were finally enrolled. Honey consumption was assessed by a
      Food Frequency Questionnaire (FFQ) and apoptosis was detected by TUNEL technique.
      We tested polynomial curve to find the best fit between honey consumption and
      apoptosis. RESULTS: A positive relation between honey consumption and apoptosis
      was found (P=0.024). Our results indicated that the final and the best fit curve
      was: apoptosis = 1.714+1.648(honey amount) - 0.533(honey amount)2 +1.833*10
      5(honey amount)7. CONCLUSION: Honey consumption had positive effects on gastric
      cancer by inducing apoptosis in gastric mucosa.

PMID- 24688919
TI  - The Relation between the Number of Hours That Authorize the Sale of Alcoholic
      Beverages and Violence.
AB  - BACKGROUND: La Victoria was considered, the most violent area in Lima City, the
      local government enforced a public policy regarding number of hours for selling
      of alcoholic beverages in January 2007. The study was designed to compare its
      results in Violence between one district with the law and other without the law.
      METHODS: This retrospective cross-sectional was an ecological study with a
      chronological and geographical comparison between La Victoria, with the
      restriction and Cercado de Lima without the ban. The participants in the study
      were patients from a local National Hospital, with aggressions from fighting, or
      were wounded in traffic accidents, and violent death bodies at National Institute
      of Legal Medicine. Data were analyzed, using clinical histories (2006 vs. 2007-8)
      and necropsies (2005-6 vs. 2007-8) RESULTS: The reduction of aggression rates at
      La Victoria in 2007 and 2008 in comparison to 2006, were 40.7% and 36.4%
      respectively (P< 0.05). It was related to the number of hours of liquor
      authorized selling Y= -11.25+27.32 X (P<0.05). There was a reduction of 44% in
      homicide (P<0.05) and 35% in suicide rates between biennia's. The female/ male
      ratio of homicides changed from 1/7.3 to 1/4.6. A significant increase in the
      rate of alcohol positive dead bodies was observed (20.3% to 41.5%), (Relative
      Risk (RR) = 2.03, (95% Confidence Interval (CI) = (1.09-3.8), chi(2)(1)=5.24, (
      P< 0.05). CONCLUSIONS: The reduction of violence was probably due to the ban,
      indicating the importance of programs to control alcohol consumption which lead
      to decrease the rate of violence and its' consequences like homicides, impulsive
      violence.

PMID- 24688920
TI  - Impact of Vitamin E Supplementation on Blood Pressure and Hs-CRP in Type 2
      Diabetic Patients | doi: 10.5681/hpp.2012.009.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major public health problem
      worldwide. Hypertension and inflammation are well recognized as risk factors for
      the macrovascular complications of diabetes. The aim of this study was to assess
      the impact of vitamin E supplementation on blood pressure (BP), serum high
      sensitivity C-reactive protein (hs-CRP) and fasting blood glucose in patients
      with T2DM. METHODS: In a double blind, randomized, controlled clinical trial, 83
      patients with T2DM were divided randomly into two groups of vitamin E (400 mg/d,
      n=42) and placebo (n=41). All patients received the pearls for 8 weeks. Baseline
      and eighth week BP, serum hs-CRP, fasting blood glucose, anthropometric and
      dietary intake data were obtained from each patient. Data were analyzed using
      SPSS version 11.5.   RESULTS: Vitamin E supplementation significantly increased
      serum levels of vitamin E (P < 0.001) and decreased mean arterial pressure and
      fasting blood glucose (P = 0.047, P = 0.028, respectively) in vitamin E group as
      compared with placebo group. A significant decrease in systolic blood pressure
      and diastolic blood pressure was observed in the vitamin E group comparing with
      baseline values (all P < 0.01). There were no significant changes in serum hs-CRP
      in both of the studied groups. CONCLUSION: Vitamin E had beneficial effects on
      serum vitamin E, BP and blood glucose in patients with T2DM. Improvement in BP
      and glucose control may contribute to reducing complications of diabetes
      including cardiovascular risk in these patients.

PMID- 24688921
TI  - Low back pain in diabetes mellitus and importance of preventive approach.
AB  - BACKGROUND: Musculoskeletal pain is known to be a common problem in diabetic
      patients. In spite of this fact, there is little information about epidemiology
      aspect of Low Back Pain (LBP) and necessity of taking preventive approach in
      diabetic patients. The aim of this study was to determine the prevalence of LBP
      in diabetic patients and its comparison with non-diabetic subjects. METHODS: Low
      back pain frequency was examined among 317 diabetic patients referred to
      endocrine clinic, Sina Hospital, Tabriz city, Iran during 3 months interval. The
      control group included 100 participants who were parents of students of Tabriz
      University. All participants were asked to fill out a questionnaire including
      Roland Morris Disability Questionnaire (RMDQ) and Face Pain Scale (FPS). RESULT:
      Of the 317 diabetic patients, 63.4% (201) reported LBP while in non-diabetic
      group was 47% (47).The average functional disability in diabetic group was 9
      while in control group was 7. Inter-correlation between low back pain intensity
      scale and functional disability were significant (r=0.52, P<0.01). DISCUSSION:
      Low back pain is a common problem in diabetic patients in terms of intensity,
      frequency and functional level of disability.

PMID- 24688922
TI  - Effectiveness of an Ergonomics Training Program on Decreasing Work-Related
      Musculoskeletal Disorders Risk among Video Display Terminals Users.
AB  - BACKGROUND: According to the findings of several studies conducted on work
      related musculoskeletal disorders (WMSDs) among the video display terminals
      (VDTs) users, Prevention of these disorders among this population is a challenge
      for many workplaces today. Ergonomically Improving of VDT workstations may be an
      effective and applicable way to decrease the risk of WMSDs. This study evaluated
      the effect of an ergonomics-training program on the risk of WMSDs among VDT
      users. METHODS: This study was conducted among a large group of computer users in
      SAPCO industrial company, Tehran, Iran (84 persons with 29.85&plusmn;11.2 years
      of age and with 6.98&plusmn;2.54 years of experience). An active ergonomics
      training program was designed and implemented during 14 days to empower the VDT
      users and involve them in improving their workstations. The direct observational
      RULA (Rapid Upper Limb Assessment) method was used in pre and post-intervention
      stages to evaluate the risk of WMSDs among participants. RESULTS: The RULA final
      scores showed that 18.8 % of VDT users were at action level 2, 63.5% at action
      level 3 and 17.6% at action level 4 before any intervention. In addition, 8.2% of
      users were at action level 1, 44.7% at action level 2, 42.4% at action level 3
      and 4.7% at action level 4 at the post-intervention stage. The results of
      Wilcoxon statistical test indicated that RULA scores ere decreased significantly
      after interventions (P < 0.05) and consequently, decreased risk of WMSDs.
      CONCLUSION: Active ergonomics training programs can be used effectively to
      improve the VDT workstations and decrease the risk of musculoskeletal disorders
      among VDT users.

PMID- 24688924
TI  - Corrosion and scaling potential in drinking water distribution system of tabriz,
      northwestern iran.
AB  - BACKGROUND: This paper discusses the corrosion and scaling potential of Tabriz
      drinking water distribution system in Northwest of Iran. Internal corrosion of
      piping is a serious problem in drinking water industry. Corrosive water can cause
      intrusion of heavy metals especially lead in to water, therefore effecting public
      health. The aim of this study was to determine corrosion and scaling potential in
      potable water distribution system of Tabriz during the spring and summer in 2011.
      METHODS: This study was carried out using Langlier Saturation Index, Ryznar
      Stability Index, Puckorius Scaling Index, and Aggressiveness indices. Eighty
      samples were taken from all over the city within two seasons, spring, and summer.
      Related parameters including temperature, pH, total dissolved solids, calcium
      hardness, and total alkalinity in all samples were measured in laboratory
      according to standard method manual. For the statistical analysis of the results,
      SPSS software (version 11.5) was used RESULTS: The mean and standard deviation
      values of Langlier, Ryznar, Puckorius and Aggressiveness Indices were equal to 
      0.68 (+/-0.43), 8.43 (+/-0.55), 7.86 (+/-0.36) and 11.23 (+/-0.43), respectively.
      By survey of corrosion indices, it was found that Tabriz drinking water is
      corrosive. CONCLUSION: In order to corrosion control, it is suggested that
      laboratorial study with regard to the distribution system condition be carried
      out to adjust effective parameters such as pH.

PMID- 24688923
TI  - Perceptions of medical sciences students towards probiotics.
AB  - BACKGROUND: Regarding the importance of probiotics in prevention of different
      diseases, the knowledge of people particularly health-related professionals about
      the beneficial effects and availability of probiotic products is important.
      Considering the limited studies, the present study was conducted to assess the
      knowledge of medical sciences students as future provider of health information
      about probiotics in Tabriz, Iran. METHODS: This cross-sectional study was carried
      out on 296 medical sciences students from different faculty majors with mean age
      of 22 &plusmn; 4 years. The students completed two self-administered
      questionnaires; the one was about the demographic characteristics and the other
      one with nine closed questions as for knowledge as well as probiotics and their
      health effects and 2 questions related to availability of probiotic products.
      Scoring of 9 knowledge questions was divided to three sections 0-3, 4-6, 7-9 and
      classified as poor, acceptable and good, respectively. The Chi-square test was
      used to examine the differences in knowledge of the students across different
      gender, major and degree groups. RESULTS: Six percent of students had poor, 43%
      acceptable, and 51% good knowledge. Total mean&plusmn;(SD) of knowledge was 6.25
      &plusmn;1.6 . Answers of students about the availability of probiotic products
      were 36.9% low, 48.1% moderate, and 15% high. Comparison of knowledge result
      between different major and degree groups was statistically significant (P<0.05).
      CONCLUSION: Although students had approximately acceptable level of knowledge
      about probiotics and their health effects, their awareness about common available
      form of probiotic products was low. The use of efficient co-educational materials
      such as teaching new findings for students may be beneficial.

PMID- 24688925
TI  - Ergonomics/Human factors needs of an ageing workforce in the manufacturing
      sector.
AB  - BACKGROUND: As the effects of demographic transition are realised around the
      world, many in-dustrial societies are facing the effects of a baby boom
      generation, increased life expectancies, decreased birth rates and recent changes
      to retirement legislation with the result that older work!ers are set to comprise
      a greater proportion of the labour force. METHODS: This paper reviews the
      evidence for the physical and cognitive factors that characterise an ageing
      workforce in manufacturing. From an ergonomics and human factors (E/HF)
      pers!pective, characteristics of manufacturing tasks and the effects of ageing
      provide an insight into how the industry will have to adapt to support the user
      needs of the older worker in the future. The approach taken is drawn from
      Ilmarinen's framework of age, experience, and work performance, from which
      specific E/HF issues are explored. RESULTS: There would appear to potential to
      support physical decline in older workers within manufacturing jobs through
      increased mechanisation and automation; however, those factors associated with
      cognitive human factors are less clear. Increased mechanisation and automation
      can place greater loads and demands on the older worker where cognitive decline
      is more subtle and varied between workers. CONCLUSION: Using historical and
      contemporary findings and the relationship between age, experience, and work
      performance is redrawn to include both cognitive skills and physical attributes
      to provide recommendations for future job design and worker needs.

PMID- 24688926
TI  - Factors that Facilitate and Impede Effective Knowledge Translation in Population
      Health Promotion: Results from a Consultation Workshop in Iran.
AB  - BACKGROUND: The workshop that this paper reports, held in Iran in May of 2011, at
      the 1st Inter-national and 4th National Congress on Health Education and
      Promotion, had three main objec-tives: 1) to introduce participants to the
      knowledge translation (KT) concept, along with its mod-els and methods; 2) to
      enhance participants' knowledge of how KT could apply to public health education
      and promotion ; and 3) to learn from different participating stakeholder groups
      about the factors that facilitate or impede effective KT in public health
      education and promotion in Iran. METHODS: The workshop consisted of three
      components: introducing the KT concept, assessing the KT capacity of
      participants, and facilitating a discussion of the important contextual factors
      that promote and impede effective KT. Of the 26 individuals from across the
      country participat-ing in the workshop, 17 took part in a KT capacity assessment
      activity. They classified them-selves into one of the following three stakeholder
      groups: administrators and policymakers (n=6), practitioners (n=2), and
      researchers (n=9). RESULTS: There were different capacities for KT across the
      three stakeholder groups. The re-ported challenges for effective KT include "lack
      of resources and funding"; "lack of time"; "poor quality of relationships and
      lack of trust between health policymakers, administrators, re-searchers, and
      clinicians"; "inadequate skills possessed by healthcare professionals and adminis
      trators for assessment and adaptation of research findings"; and "poor
      involvement of commu-nity partners in the research process." DISCUSSION: There is
      a great need to develop effective strategies to overcome the reported barri-ers
      for effective KT.

PMID- 24688927
TI  - Health belief model and reasoned action theory in predicting water saving
      behaviors in yazd, iran.
AB  - BACKGROUND: People's behaviors and intentions about healthy behaviors depend on
      their beliefs, values, and knowledge about the issue. Various models of health
      education are used in deter!mining predictors of different healthy behaviors but
      their efficacy in cultural behaviors, such as water saving behaviors, are not
      studied. The study was conducted to explain water saving beha!viors in Yazd, Iran
      on the basis of Health Belief Model and Reasoned Action Theory. METHODS: The
      cross-sectional study used random cluster sampling to recruit 200 heads of
      households to collect the data. The survey questionnaire was tested for its
      content validity and reliability. Analysis of data included descriptive
      statistics, simple correlation, hierarchical multiple regression. RESULTS: Simple
      correlations between water saving behaviors and Reasoned Action Theory and Health
      Belief Model constructs were statistically significant. Health Belief Model and
      Reasoned Action Theory constructs explained 20.80% and 8.40% of the variances in
      water saving beha-viors, respectively. Perceived barriers were the strongest
      Predictor. Additionally, there was a sta!tistically positive correlation between
      water saving behaviors and intention. CONCLUSION: In designing interventions
      aimed at water waste prevention, barriers of water saving behaviors should be
      addressed first, followed by people's attitude towards water saving. Health
      Belief Model constructs, with the exception of perceived severity and benefits,
      is more powerful than is Reasoned Action Theory in predicting water saving
      behavior and may be used as a framework for educational interventions aimed at
      improving water saving behaviors.

PMID- 24688928
TI  - Nutritional status in patients with major depressive disorders: a pilot study in
      tabriz, iran.
AB  - INTRODUCTION: This study was conducted to assess the nutritional status in
      Iranian major depres!sive disorder patients. We also determined the relationship
      between nutrients intake with depres!sion severity. METHODS: Seventy major
      depressive patients were selected randomly from outpatient depressive subjects,
      referred to Razi Psychiatry Hospital in Tabriz, Iran in 2007. Dietary intakes
      were rec!orded and compared with dietary reference intakes (DRIs). Definition of
      the disease and its se!verity were according to DSM-IV-TR and Hamilton Depression
      Rating Scale, respectively. Nu!tritionist III program, Chi-square, correlation
      and t-test were used for data analyses. Demo!graphic, clinical and laboratory
      data were analyzed using SPSS software for windows (ver!sion13.0). RESULTS:
      According to dietary analysis, 11.4% and 55% of patients had dietary protein and
      energy deficiency, respectively. 97.1% and 95.7% of patients had less folate and
      B12 intakes than recom!mended dietary allowances. The mean (Mean +/- SD) for
      plasma folate and B12 was 5.18+/-6.11 ng/ml and 389.05+/-346.9 pg/ml,
      respectively. Low plasma folate and B12 was observed in 51.4% and 50.0 % of
      patients, respectively. There was no significant relationship between blood
      folate and B12 levels with depression severity. Similarly, nutrients intake had
      no effect on depression se!verity. CONCLUSION: Low plasma concentrations and low
      dietary intakes of folate and B12 are common among Tabrizian depressive patients.
      It seems that nutritional intervention for increasing folate and vitamin B12
      intake must be considered as health promotive and preventative program for
      patients suffering from depression disorders.

PMID- 24688929
TI  - Exploring the etiologic factors and dynamics of prescription drug abuse in
      southwest virginia.
AB  - BACKGROUND: Prescription drug abuse in Southwest Virginia is a serious problem
      affecting indi-viduals, families, and communities. The aim of this study was to
      characterize and understand the extent of the prescription drug abuse problem in
      Southwest, Virginia as well as the dynamics that surround that abuse. More
      specifically, the study focused on learning the extent of the problem along with
      which prescription drugs are typically used prior to entering treatment, reasons
      for prescription drug and methadone abuse, and the sources for prescription drug
      use, misuse and abuse. METHODS: Mixed methodology was employed which included
      surveying methadone clinic con-sumers at two treatment clinics in Southwest,
      Virginia and seven focus field interviews of key community stakeholders. RESULTS:
      The extent of prescription drug abuse is high and that the demographics of
      prescription drug users are getting younger and now involve more males than
      females. Oxycodone, hydroco!done, methadone, and morphine were the most commonly
      used drugs prior to enrollment in the clinics with over one-half of methadone
      maintained consumers reporting that they had abused benzodiazepines along with
      opioids. Focus groups and clinic consumer data highlighted the key etiological
      factors in prescription drug abuse: use (due to workforce related injuries)
      turning to abuse, wanting to get high, overprescribing and physician issues, lack
      of information, and cultural acceptance of drug taking as problem solving
      behavior. The two most common sources for the abused prescription drugs were
      physicians and street dealers. CONCLUSIONS: A constellation of conditions have
      led to the epidemic of prescription drug abuse in Southwest Virginia, including
      poverty, unemployment and work-related injuries, besides, public health education
      programs on the dangers of prescription opiate misuse and abuse are urgently
      needed.

PMID- 24688930
TI  - Awareness of Parents about Characteristics of a Healthy School Backpack.
AB  - BACKGROUND: The issue of knowledge on school backpacks among parents has received
      little attention. The objectives of this study were to assess school backpack
      carriage and its consistency with parents' knowledge about children friendly
      school backpacks. METHODS: This was a randomized cross-sectional study. Totally
      307 elementary school children and 250 parents were recruited to assess parental
      knowledge about standard school backpacks in 2010. Data collection were carried
      out on an unscheduled day in order to, children and their par!ents prepared
      school backpacks based on their own previous habits and behaviors. All
      statistical analyses were performed using version 16.0 of the statistical
      software package SPSS Results: Approximately, 132 (51.6%) of the parents were not
      aware of the recommended weight limit for carrying school backpacks and 144
      (56.3%) were not aware that the size of the backpack must be proportionate to the
      upper back region. Significant difference was found for the mean score of
      awareness of a safe and standard school backpack between fathers and mothers:
      fathers had more knowledge about school backpack carriages in comparison with
      mothers (P<0.001). CONCLUSION: Children, parents and teachers should be educated
      about the characteristics of a standard backpack, different strategies. Parents
      are the best advocates for safety promotion and should represent the group most
      likely to help to significantly reduce backpack related injuries among school
      children by selecting safe school backpacks, supervising school backpack carrying
      and checking backpack weights.

PMID- 24688931
TI  - Knowledge, Attitude and Practice between Medical and Non-Medical Sciences
      Students about Food Labeling.
AB  - BACKGROUND: Considering the significant role of consumers' awareness about food
      labels in making healthy food choices, this study was designed to assess the
      knowledge, attitude and prac!tice of university students about food labeling.
      METHODS: In this cross-sectional study, 332 students aged 18-25 yr in five
      different academic majors (including Nutrition, Public Health, Health Services
      Administration, Paramedical and En!gineering) were asked to complete an approved
      questionnaire contained fifteen questions. The chi-square test was applied to
      examine the differences across various major groups. RESULTS: 89.2% of the
      students believed that food labels had effect on nutritional awareness. 77.4%
      were agreed with the usefulness of the food labels and 79.2% did not feel that
      nutrition claims on food label were truthful. For 84% of students, the expiry
      date and storage conditions information were the most important informational
      cues to appear on the food labels. From 47.6% of students who reported the use of
      nutrition facts label in their often or always shopping; only 32.3% used the
      information on labels to fit the food into their daily diet. Surprisingly, fatty
      acids were the least noteworthy items (1.9%) on nutrition facts labels. Regarding
      students' major, there was significant difference in their knowledge, attitude
      and practice about truth of the nutri!tion claims, using food labels and
      importance of health claims (P<0.05). CONCLUSION: Food labels were more useful
      tools for students and had an effect on their nutri-tional awareness. Designing
      and implementation of the educational programs in order to increase the level of
      knowledge about food labels is suggested.

PMID- 24688932
TI  - Validation of the Use of Dried Blood Spot (DBS) Method to Assess Vitamin A
      Status.
AB  - BACKGROUND: Vitamin A deficiency is an important dietary deficiency in the world.
      Thus, the ne!cessity of screening for deficient populations is obvious. This
      paper introduces a fast, cheap and relatively reliable method called "dried blood
      spot" (DBS) method in screening the deficient populations. The validity of this
      method for retinol measurement was investigated. METHOD: The "precision" and
      "agreement" criteria of the DBS method were assessed. The preci!sion was
      calculated and compared with those of plasma using F-test. The agreement was
      eva!luated using Bland-Altman plot. RESULTS: The imprecision of retinol
      measurements in dried spots was not significantly different from those of the
      control (plasma). A good correlation coefficient (r2=0.78) was obtained for dried
      spots' retinol measurements versus plasma's retinol analysis (P < 0.01). Paired t
      test showed no significant difference between the DBS and retinol methods on a
      group level. Imprecision of DBS measurement was acceptable, compared to that of
      the plasma method. The difference be!tween these two methods was not
      statistically significant on a group level. CONCLUSION: Application of DBS
      standard samples, in which a part of the plasma was replaced with the artificial
      plasma, was shown to be a reliable calibration mean for retinol measurements in
      DBS samples. Retinol in dried spots was stable for 90 days. Overall, the DBS
      method provided a precise measurement of retinol, showing results that were
      comparable with the measurement of retinol in plasma.

PMID- 24688933
TI  - Factors influencing the job satisfaction of health system employees in tabriz,
      iran.
AB  - BACKGROUND: Employees can be counseled on how they feel about their job. If any
      particular dimension of their job is causing them dissatisfaction, they can be
      assisted to appropriately change it. In this study, we investigated the factors
      affecting job satisfaction from the perspective of employees working in the
      health system and thereby a quantitative measure of job satisfaction. METHODS:
      Using eight focus group discussions (n=70), factors affecting job satisfaction of
      the employees were discussed. The factors identified from literature review were
      categorized in four groups: structural and managerial, social, work in it-self,
      environmental and welfare factors. RESULTS: The findings confirmed the
      significance of structural and managerial, social, work in it-self, environmental
      and welfare factors in the level of job satisfaction. In addition, a new factor
      related to individual characteristics such as employee personal characteristics
      and development was identified. CONCLUSION: In order to improve the quality and
      productivity of work, besides, structural and managerial, social, work in it
      self, environmental and welfare factors, policy makers should be taken into
      account individual characteristics of the employee as a factor affecting job
      satisfaction.

PMID- 24688934
TI  - Benefits of omega-3 Fatty acids supplementation on serum paraoxonase 1 activity
      and lipids ratios in polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder
      associated with increased risk of cardiovascular disease. The purpose of this
      study was to investigate the ef!fects of omega-3 fatty acids on serum paraoxonase
      1 activity and lipids ratios in polycystic ovary syndrome. METHODS: This double
      blind randomized controlled clinical trial was conducted on 64 PCOS pa!tients
      with 20-35 years old. Thirty two of the subjects had taken 4 g/day omega -3 fatty
      acids and 32 patients were given placebo for 8 weeks. Fasting blood samples,
      anthropometric measure!ments and dietary intakes were collected at the beginning
      and the end of the study. Serum total cholesterol, triglyceride, and HDL-C were
      measured using the enzymatic methods. LDL-C con!centration was calculated by the
      Friedewald formula and arylesterase activity of serum PON1 was measured. Data
      were analyzed using SPSS software. RESULTS: Omega-3 fatty acids significantly
      decreased TC/HDL-C and LDL-C/HDL-C ratios (P = 0.009 for both) and significantly
      increased serum PON1 activity (P = 0.048) compared with placebo. Changes in
      TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at
      the end of the study in comparison to placebo group. Reduction in TC/HDL-C, LDL
      C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also
      significant in omega-3 fatty acids group at the end of the study compared with
      baseline values (P <0.001, P < 0.001, P = 0.004, and P = 0.001, respectively).
      CONCLUSION: Omega-3 fatty acids may decrease the risk for cardiovascular disease
      through the improvement in paraxonase-1 activity and reduction in some lipids
      ratio in PCOS women.

PMID- 24688935
TI  - Heavy metals concentrations in groundwater used for irrigation.
AB  - BACKGROUND: The main objective of this study was characterization of selected
      heavy metals concentrations (Lead, cadmium, copper, zinc, nickel and chromium) in
      groundwater used for ir-rigation in Tabriz City's countryside. METHODS: After
      consulting with the experts of agriculture department and site survey, 38 irriga
      tion water samples were taken from different farms (34 wells) without primary
      coordination with farm owners. All of samples were acidified to achieve pH~2 and
      then were concentrated from 10 to 1 volume. The concentrations of Cd, Pb, Cu, Cr,
      Ni, and Zn in the samples (totally 228) were determined with a flame atomic
      absorption spectrophotometer. RESULTS: In none of 38 farms, irrigation with
      surface runoff and industrial wastewater was ob-served. The average
      concentrations of Cd, Pb, Cu, Cr, Ni, and Zn in the irrigated water were
      de!termined 6.55, 0.79, 16.23, 3.41, 4.49, and 49.33ug/L, respectively. The
      average and even maxi!mum concentrations of heavy metals in the irrigation water
      at the studied area were less than toxicity threshold limits of agricultural
      water. CONCLUSION: Currently, not using of surface runoff and industrial
      wastewater as irrigation water by farmers indicates that the controlling efforts
      by authorities have been effective in the area. Water used for irrigation of the
      farms and groundwater of the studied area are not polluted with heavy metals and
      there is no risk from this viewpoint in the region.

PMID- 24688936
TI  - Anthropometric indices added the predictive ability of iron status in prognosis
      of atherosclerosis.
AB  - BACKGROUND: Abnormal homeostasis of iron such as deficiency or overload is
      associated with the pathogenesis of cardiovascular disease (CVD). Another risk
      factor for CVD is obesity whose added predictive ability to iron status has been
      assessed by few study. This study aimed to eva!luate the effect of adding
      anthropometric indices to a model based on iron status as risk factors of CVD.
      METHODS: This cross-sectional study included 140 adult women aged 18-50 years
      randomly se-lected from Sheikhorrais Clinic that is one of the Tabriz University
      sub-specialized clinics in 2011. Anthropometric indices, carotid intima-media
      thickness (CIMT) and body iron status were measured by standard protocol, non
      invasive ultrasound and concentrations of serum iron, ferri!tin, TIBC (Total iron
      Binding Capacity) and complete blood cell counts (CBC), respectively. In!tegrated
      discriminatory improvement index (IDI) and net reclassification improvement index
      (NRI) were used as the measures of added predictive ability of anthropometric
      measures to the iron statues. RESULTS: IDI (SE) after adding Waist Circumference
      (WC), Waist to Heap Ratio (WHR), Waist to Height Ratio (WHtR), Body Mass Index
      (BMI) and Body fat (%) to base model was 0.12 (0.028), 0.09 (0.026), 0.12
      (0.028), 0.07 (0.022) and 0.10 (0.026) respectively. The NRI (SE) was 0.10
      (0.065) for WC, 0.03 (0.058) for WHR, 0.07 (0.067) for WHtR, 0.05 (0.067) for
      BMI, and 0.08 (0.064) for Body fat. CONCLUSIONS: Anthropometric indices could
      significantly add to the predictive ability of the iron statues, with highest IDI
      when WC and WHtR were added to the base model. It suggests that by adding WC and
      WHtR to the iron status lead us to a more optimal model for predicting the
      ini!tial stage of atherosclerosis.

PMID- 24688937
TI  - Oxalate content of different drinkable dilutions of tea infusions after different
      brewing times.
AB  - BACKGROUND: The aims of this study were to determine the effect of different
      brewing times and diluting on oxalate content of loose-packed black teas consumed
      in Tabriz, Iran. METHODS: The oxalate content of black teas after brewing for 5,
      10, 15, 30, 60 minutes was measured in triplicate by enzymatic assay. In order to
      attain the most acceptable dilution of tea infusions, tea samples which were
      brewed for 15, 30 and 60 minutes were diluted two (120 ml), three (80 ml) and
      four (60 ml) times respectively. RESULTS: There was a stepwise increase in
      oxalate concentrations associated with increased brewing times (P< 0.001) with
      oxalate contents ranging from 4.4 mg/240 ml for the 5 min to 6.3 mg/240 ml for 60
      min brewing times, respectively. There were significant differences between the
      mean oxalate content of different dilutions after brewing for 15, 30 and 60
      minutes (P< 0.001). CONCLUSION: The oxalate content of Iranian consumed black tea
      after different brewing times and different dilution was below the recommended
      levels. Therefore, it seems that consumption of black tea several times per day
      would not pose significant health risk in kidney stone patients and susceptible
      individuals.

PMID- 24688938
TI  - Iranian Expert Opinion about Necessary Criteria for Hospitals Management
      Performance Assessments.
AB  - BACKGROUND: Managers in the hospital should have enough managerial skill to be
      coordinated with the complex environment. Defining a competency framework
      assessment for hospital man-agement will help to establish core competencies for
      hospital managers. The aim of this study was to develop concrete and suitable
      performance assessment criteria using expert's view. METHODS: In this qualitative
      study in total, 20 professionals participated in the interview and Fo!cus Group
      Discussions (FGD). Two of informants were interviewed and 18 professionals
      par!ticipants in three focus group discussions. Discussions and interviews were
      well planned, the FGD environments were suitable and after interviews completion
      the notes were checked with participant for completeness. Thematic analysis
      method was used for the analysis of qualitative data. RESULTS: Findings from 3
      FGDs and 2 semi structured interviews done with 20 professionals were categorized
      accordance to themes. The findings were classified in 7 major and 41 sub themes.
      The major themes include competency related to planning, organization and staff
      per-formance management, leadership, information management, and clinical
      governance and per-formance indicators. CONCLUSION: All participants had hospital
      administration experience; so their explanation impor!tant in identifying the
      criteria and developing hospital managers' performance assessment tool. In
      addition to professional perspectives and studies done in other countries, in
      order to design this kind of tools, it is necessary to adopt the obtained
      findings to the local hospital conditions.

PMID- 24688939
TI  - Effects of royal jelly supplementation on body weight and dietary intake in type
      2 diabetic females.
AB  - BACKGROUND: The objective of the current study was to assess the effects of royal
      jelly supple-mentation on body weight, total daily energy and macronutrients
      intakes in type2 diabetic fe-males. METHODS: In this randomized clinical trial,
      fifty female volunteers with type2 diabetes were as-signed into the supplemented
      (n=25) and placebo (n=25) groups, given a daily dose of 1000 mg royal jelly soft
      gel or placebo, for 8 weeks, respectively. Before and after the intervention,
      body weight and height of subjects were measured and body mass index was
      calculated. Dietary intake of patients was assessed using 24-hour food recall
      questionnaire for three non consecutive days (including 1 weekend day) and
      analyzed with Nutritionist IV software. The normally distributed data were
      compared using paired and independent t-tests, where appropriate. RESULTS: Royal
      jelly supplementation significantly (P<0.01) decreased the mean body weight
      (72.45+/-4.42 vs. 71.00+/-6.44 kg) while it increased insignificantly in placebo
      group (73.02+/-6.44 vs 73.52+/-6.80 kg). Royal jelly supplementation resulted in
      significant decrease of mean daily total energy (P<0.01) and carbohydrate
      (P<0.01) intakes, while in placebo group the mean daily total energy and fat
      intakes were increased significantly (P<0.05). CONCLUSION: Supplementation with
      royal jelly may be beneficial in weight management of di-abetic patients.

PMID- 24688940
TI  - Confirmation of monod model for biofiltration of styrene vapors from waste flue
      gas.
AB  - BACKGROUND: The objective of this research was to investigate the kinetic
      behavior of the biofil!tration process for the removal of styrene. METHODS: A
      three stage compost based biofilter was inoculated with thickened activated
      sludge. The reaction order rate constants were obtained from continuous
      experiments and used as the specific growth rate for the Monod equation. RESULTS:
      The measured concentration profiles show a linear dependence on the bed height in
      the biofilter at higher loadings, such as 75 and 45 g m-3 h-1. This is the
      condition of reaction limitation for a reaction with zero-order kinetics. From
      the experimental data, maximum elimination capac!ity (ECmax) was estimated to be
      44, 40 and 26 g m-3 h-1 at empty bed retention times (EBRTs) of 120, 60 and 30 s,
      respectively. However, at lower loadings, the measured concentration profile of
      the biofilter is one of exponential increase, which is the condition of both
      reaction and diffusion limitations for a reaction with zero-order kinetics.
      Maximum elimination capacities found from the experimental results were the same
      as Monod model predictions. Both the experimental re!sults and the model
      predictions showed the influence of EBRT on the removal rate of styrene,
      particularly for the highest loading rate. CONCLUSION: In terms of the practical
      applications of the proposed models have the advantage of being simpler than
      Monod kinetics and Monod kinetics requires a numerical solution.

PMID- 24688941
TI  - Nitrate Determination of Vegetables in Varzeghan City, North-western Iran.
AB  - Background Vegetables play an important role in human nutrition. Nitrate content
      is a signifi-cant quality criterion to determine characteristic of vegetables.
      About 80% of nitrate intake in human is from vegetables and fruits. High dietary
      intake of nitrate is seen as an undesirable be-cause of its association with
      gastric cancer and infantile methemoglobinemia. Varzeghan, North!western Iran is
      one of the cities with high Age-standardized incidence rates (ASR) of gastric
      can!cer in Iran. Currently, in Varzeghan there is no available and accurate
      information describing ni!trate concentration as one of the important risk
      factors of vegetables for human consumption. Methods In this cross sectional
      study totally 11 types of vegetables (cabbage, lettuce, spinach, parsley,
      coriander, dill, leek, fenugreek, tarragon, fumitory and mint) from several
      different green!grocery of Varzeghan were collected in spring (April) and autumn
      (November and December) 2011 and their nitrate contents were analyzed. Results
      Mean nitrate contents at the above noted fresh vegetables were 161, 781, 83, 707,
      441, 501, 1702, 684, 805, 772 and 191 mg NO3-kg-1 respectively. In none of the 11
      fresh vegetables nitrate content were not more than established limitations.
      Conclusion Nitrate concentrations were below of others reported at different
      countries. The mean concentration of nitrate at all vegetables in autumn was
      higher than in spring significantly. 

PMID- 24688942
TI  - Prioritizing public- private partnership models for public hospitals of iran
      based on performance indicators.
AB  - BACKGROUND: The present study was conducted to scrutinize Public- Private
      Partnership (PPP) models in public hospitals of different countries based on
      performance indicators in order to se-lect appropriated models for Iran
      hospitals. METHODS: In this mixed (quantitative-qualitative) study, systematic
      review and expert panel has been done to identify varied models of PPP as well as
      performance indicators. In the second step we prioritized performance indicator
      and PPP models based on selected performance indicators by Analytical Hierarchy
      process (AHP) technique. The data were analyzed by Excel 2007 and Expert Choice11
      software's. RESULTS: In quality - effectiveness area, indicators like the rate of
      hospital infections (100%), hospital accidents prevalence rate (73%), pure rate
      of hospital mortality (63%), patient satisfaction percentage (53%), in
      accessibility equity area indicators such as average inpatient waiting time
      (100%) and average outpatient waiting time (74%), and in financial - efficiency
      area, indicators including average length of stay (100%), bed occupation ratio
      (99%), specific income to total cost ratio (97%) have been chosen to be the most
      key performance indicators. In the pri!oritization of the PPP models clinical
      outsourcing, management, privatization, BOO (build, own, operate) and non
      clinical outsourcing models, achieved high priority for various performance
      in!dicator areas. CONCLUSION: This study had been provided the most common PPP
      options in the field of public hospitals and had gathered suitable evidences from
      experts for choosing appropriate PPP option for public hospitals. Effect of
      private sector presence in public hospital performance, based on which PPP
      options undertaken, will be different.

PMID- 24688943
TI  - Working Conditions in Carpet Weaving Workshops and Muscu-loskeletal Complaints
      among Workers in Tabriz - Iran.
AB  - BACKGROUND: Carpet weaving operations usualy involve poor working conditions that
      can lead to the development of musculoskeletal disorders (MSDs). This study
      investigated MSDs among car!pet weavers in relation to working conditions from
      workers' view in Tabriz City, Northwest Iran. METHODS: This cross-sectional and
      descriptive study was conducted in city of Tabriz, Iran. Data were col!lected
      using interviews and questionnaires. The study population consisted of 200
      randomly selected healthy weavers from twenty five active carpet weaving
      workshops. RESULTS: The results showed a high prevalence of musculoskeletal
      problems among the study population. The most commonly affected body areas were
      neck, lower back, ankles/feet, hands/wrists, upper back, shoulders and knees,
      respectively. More than half of the weavers were not satisfied with the thermal
      con!dition, noise level and cleanliness of the air in the workshops. The result
      indicated a significant relation!ship between upper back symptoms and daily
      working time and between lower back symptoms and the numbers of rows of knots
      woven in a day. Weavers' satisfaction with hand tools shape and thermal
      condi!tion of the workshops were associated with lower back symptoms, whereas
      satisfaction with weaving looms were associated with upper back complaints.
      CONCLUSION: The poor working condition of hand-woven carpet workshops such as
      environmental con!ditions and work station design and tools should be the subject
      of ergonomics interventions.

PMID- 24688944
TI  - Participation in cervical screening by older asian and middle eastern migrants in
      new South wales, australia.
AB  - BACKGROUND: There is little information on the detailed patterns of cervical
      screening uptake in older migrant women in Australia. This linkage study was
      performed to assess cervical screening participation in older migrants. METHODS:
      We linked year 2000-2001 records for 14,228 Middle Eastern/Asian-born women 40-64
      years of age, and an age and area matched random sample of 13,939 Australian-born
      women in the New South Wales (NSW) Admitted Patients Data Collection (APDC),
      which records country of birth, to screening register records. Screening
      behaviour after 1st July 2001 was assessed in women without a recorded prior
      cervical abnormality RESULTS: Compared to Australian-born women, women born in
      South Central Asia had a lower screening participation rate (odds ratio for being
      screened at least once within a 3 year period 0.78, 95% CI 0.70-0.88). However,
      participation appeared relatively higher (17%-25%) in women born in the Middle
      East or other parts of Asia. Screening increased with increasing socioeconomic
      status (SES) in Australian-born women, but this trend was not observed in the
      migrant women. When we broadly corrected for hysterectomy, the apparent excess of
      screening in women from the Middle East and other parts of Asia was substantially
      eliminated and in contrast, the apparent deficiency in screening in women from
      South Central Asia increased. CONCLUSIONS: Older women from the Middle East, and
      North East and South East Asian countries appeared to have similar overall
      screening participation to that of Australian-born women. Women from South
      Central Asia appeared less likely than Australian-born women to participate in
      cervical screening at the recommended interval.

PMID- 24688946
TI  - We need more focus on pre-disaster preparedness: early lessons learned from
      recent earthquakes in northwest of iran.

PMID- 24688945
TI  - Iran's Experience of Health Cooperatives as a Public-Private Partnership Model in
      Primary Health Care: A Comparative Study in East Azerbaijan.
AB  - BACKGROUND: Iran started a new public-private partnership model in form of health
      coopera!tives which is somehow different from other types of health cooperatives
      throughout the world. In this study we compared the performance and quality of
      health services in public health cen!ters (PHCs) and cooperative health centers
      (CHCs). METHODS: In this comparative study performance quality of two cohorts of
      public and coopera!tive health centers were compared in several health service
      delivery programs over the time pe!riod of 2001- 2002. RESULTS: Screening
      program: the rate of visited population during screening program was higher in
      CHCs. Maternal health care program: In some of studied programs CHCs had better
      results. Child health care: Most indicators were better or similar in CHCs.
      School health program and Health education: All indices were better or similar in
      CHCs. Environmental health: population based positive function was not
      significantly different for the population covered by CHCs compared to population
      covered by PHCs. MANAGEMENT: Client and staff satisfaction as well as
      participation and attitudes of personnel towards management was better in CHCs.
      Mean annual cost per capita of the covered population by PHCs was higher.
      CONCLUSION: CHCs as a public private partnership model in Iran may deliver
      preventive health care services as effective as PHCs in many fields and even
      better in some areas.

PMID- 24688947
TI  - Community Health Policy Assessment of a Rural Northeast Missouri County using the
      Centers for Disease Control and Prevention's CHANGE Tool.
AB  - BACKGROUND: In order to build a framework to address policy gaps and needs,
      community's risk factors were identified and the extent to which current policies
      were in place to address the risk factors were compared. METHODS: Face-to-face
      interviews, using the US Centers for Disease Control and Prevention's CHANGE tool
      were conducted in a rural Northeast Missouri county possessing exceptionally high
      chronic disease rates to assess the factor(s) had the greatest influence on the
      rates in each sector of the community. RESULTS: The Health Care Agency sector
      possessed the most factors categorized as environmental and policy assets, and
      the Community-at-Large and Business/Worksite sectors seemed to possess the least
      environmental and policy factors categorized as assets. CONCLUSIONS: Because
      organizational policies can strongly influence community health practices and
      behaviors, collaborative leadership from the Health Care Agency sector,
      comprehensive worksite health promotion programs in the Business/Worksite and
      Community Institutions/Organizations sectors, and tobacco-free school policies
      are recommended. Multiple community sectors must work together to change not only
      behaviors but also environments in this county.

PMID- 24688948
TI  - Perceived Barriers to Weight loss Programs for Overweight or Obese Women.
AB  - BACKGROUND: In order to develop appropriate obesity control and treatment
      strategies, the key point is to understand the barriers perceived by overweight
      or obese people in trying to follow weight-loss programs. This study examined
      perceived barriers to weight-loss programs among overweight or obese women.
      METHODS: In this descriptive-analytical study, 204 overweight or obese women aged
      31.97+/- 10.62 yr, were selected randomly from the nutritional counseling centers
      in 2008 in Tabriz, Iran. The mean BMI was 33.83 +/-5.75 kg/ m2. A structured
      questionnaire including questions on barriers to weight-loss diet and physical
      activity was filled out for each participant by face-to-face interview. Height
      and weight measured objectively and demographic details were obtained. Data
      analysis carried out using multiple regression and factor analysis. RESULTS: The
      most important perceived barriers to weight-loss diets were 'situational
      barriers', stress, depression, and food craving. High educational level was
      independent determinant of situational barriers (beta=0.329, P=0.048). Employee
      women had a higher mean score on stress and depression than students and
      housewives. Lack of time and exercising lonely were the most important items of
      "External barriers" and Lack of motivation was the most important item of
      "internal barriers" to physical activity. Employment and being student were
      highly associated with external barriers (beta=1.018, P<0.001 and beta=0.541, P=
      0.002). Moreover, older women who had low educational level, perceived more
      internal barriers. CONCLUSION: Weight reducing strategies should take into
      account the specific perceived barriers to weight-loss diets faced by overweight
      or obese women, particularly situational barriers, stress and depression and food
      craving; and lack of time and lack of motivation as barriers to physical
      activity.

PMID- 24688949
TI  - Technical Quality of Maternity Care: the Pregnant Women's Perspective.
AB  - BACKGROUND: Improving adherence to care standards is one way to improve quality
      of delivered care. This study aimed to determine the degree of providers'
      adherence to maternity care standards from the perspective of pregnant women.
      METHODS: This cross-sectional study was conducted on 185 pregnant women in their
      ninth month of pregnancy who received maternity care from health centres in
      Tabriz, Iran. Participants were selected randomly from 40 health centres. Data
      collection used a researcher-developed questionnaire based on Iranian Ministry of
      Health (MOH) standards for maternity care. Questionnaire validity was reviewed
      and confirmed by 10 experts. RESULTS: About 69% of pregnant mothers during their
      9-month pregnancy received at least six items of standard maternity care. Almost
      two-thirds of participants received recommended maternity care at or above
      minimal standards for some aspect, such as the number of care during pregnancy,
      referral to health centre physician, and weight and blood pressure measurement.
      Some other services such as measuring uterus height, review for oedema and
      varicosities, referral to a dentist, listening for fetal heart sound and vaginal
      examination, were reported at very low adherence to the Ministry of Health
      guidelines Conclusion: A notable proportion of pregnant mothers reported
      receiving suboptimal care indicating significant room for improving the quality
      of maternity care based on Iranian MOH standards and guidelines. The results
      indicate potential benefits from interventions to improve health care providers
      training and the awareness of pregnant women about the standards for good
      maternity care.

PMID- 24688950
TI  - Pathways of women prisoners to jail in pakistan.
AB  - BACKGROUND: The present study aimed to examine pathways to imprisonment for women
      in Pakistan. It was hypothesized that early life victimization in women,
      problematic family relationship and economical deprivation would be significantly
      associated with criminal activities of women prisoners. METHOD: To identify the
      pathways to prison, structured interview was devised by the researchers. Sample
      comprised of 114 women prisoners enlisted from KotLakhpat jail, Lahore, Pakistan.
      RESULTS: Poverty, revenge, anger and lack of empowerment were significantly
      associated with criminal activities of women of fender. CONCLUSION: The umbrella
      of rehabilitation should also cover social and legal matters of women offenders
      along with tackling their psychological issues.

PMID- 24688951
TI  - Ergonomic assessment and musculoskeletal health of the underprivileged school
      children in pune, India.
AB  - BACKGROUND: Musculoskeletal health in schoolchildren is a global health
      problem.The objective of the current study was to assess ergonomic behavior and
      musculoskeletal health in urban poor schoolchildren in Pune, India. METHODS:
      Sixty-five (29 male students) slum dwelling schoolchildren were assessed for
      their ergonomics using a validated and reliable tool. RESULTS: Average age was 13
      years. Out of 65 students, 36 reported presence of musculoskeletal pain. In
      addition, 78.5% had bad ergonomics when lifting books.Sitting posture was poor in
      67.7%, while 50.8% demonstrated bad posture while using a computer. As far as the
      female students were concerned, it was seen that out of 36 students, 55.6%
      complained of presence of pain. Out of the 20 students who reported pain, 70% had
      a score lower than 7.5 on ergonomic score assessment (indicative of bad
      ergonomics). When the male students were considered, out of 29 students, 65.5%
      reported presence of pain. Out of the 19 students who reported pain, close to 79%
      demonstrated bad ergonomics. CONCLUSION: There is presence of musculoskeletal
      aches and pains in this underprivileged section of the society, including
      demonstration of bad ergonomics and postures while performing activities in
      school. Thus, musculoskeletal health problems exist in urban slum schoolchildren.
      It is important to identify health problems at an early stage in both boys and
      girls. Children are the future of the nation and hence, identification of health
      issues early in life and preventing them from becoming chronic is of utmost
      importance.

PMID- 24688952
TI  - Recess Activity and General Health Status among Iranian Elementary Schools'
      Pupils.
AB  - BACKGROUND: Regular and daily physical activity during childhood and at school is
      one of the important part of requirements of normal growth, development and well
      being. To achieve physical activity promotion among school child aged population
      recess as outside of class time efforts is scheduled and allows students to
      engage in physical and social activities. The purpose of the present study was to
      assess recess activities as well as status of physical activities among a sample
      of Iranian students at the primary schools. METHODS: This cross-sectional study
      was performed in four randomly selected schools from a list of 26 elementary
      schools in March, 2012 in the city of Shahindej, located in North-west of Iran.
      Participants were 439 (10-12 years) elementary schools'. Physical activity level
      by self-reporting, mental health using the parent-completed Child Health
      Questionnaire, and happiness was assessed using a Persian translated version of
      the Subjective Happiness Scale. Hierarchical logistic regression analysis was
      applied in two steps using the enter method to analyze data in the SPSS version
      17. RESULTS: Backward logistic regression analysis showed that gender of the
      parent who answered the study questions, father's education, educational grade of
      children, BMI, physical function, physical health, health status of the children
      and family function were significantly related to the children's physical
      activity level. CONCLUSION: Promoting parents' awareness and schools' staff about
      importance of physical activities especially in recess times must be an important
      part of school and community mental health promotion programs.

PMID- 24688953
TI  - Effects of high performance inulin supplementation on glycemic status and lipid
      profile in women with type 2 diabetes: a randomized, placebo-controlled clinical
      trial.
AB  - BACKGROUND: Type 2 diabetes mellitus, as a noncommunicable disease, is the main
      public health challenge in the 21st century. The prevalence of diabetes mellitus
      adjusted for the world population in Iran was 8% until the year 2010.Lipid levels
      are considered as important parameters to be evaluated, as high serum lipid
      levels are often reported as a complication in patients with diabetes mellitus.It
      is claimed that functional foods may improve complications of diabetes mellitus,
      so this study was designed to evaluate the effects of high performance inulin on
      glycemic status and lipid profile of women with type 2 diabetes. METHODS: The
      study was a randomized controlled clinical trial. Forty-nine type 2 diabetic
      females (fiber intake <30g/d, 25<BMI<35 kg/m2) were divided into two groups.
      Patients in the intervention group (n=24) received 10g/d inulin and patients in
      the control group (n=25) received 10g/d maltodextrin for 8 weeks.Glycemic status
      and lipid profile indices were measured pre and post intervention. Data were
      analyzed using SPSS software (verision11.5). Paired, unpaired t-test and ANCOVA
      were used to compare quantitative variables. RESULTS: Supplementation with inulin
      caused a significant reduction in FBS (8.50%), HbA1c (10.40%), total cholesterol
      (12.90%), triglyceride (23.60 %), LDL-c (35.30 %), LDL-c/HDL-c ratio (16.25%) and
      TC/HDL-c ratio (25.20%) and increased HDL-c (19.90%). The changes for the control
      group parameters were not significant at the end of study. CONCLUSION: Inulin may
      help to control diabetes and its complications via improving glycemic and lipid
      parameters.

PMID- 24688954
TI  - Perception of Rural and Urban Mothers about Consumption of Targeted Fortified
      Products in Jaipur, Rajasthan - India: A Cross-Sectional Study.
AB  - BACKGROUND: Food fortification is the addition of one or more essential nutrients
      to a food whether or not it is normally contained in the food, for the purpose of
      preventing or correcting a demonstrated deficiency of one or more nutrients in
      the population or specific population groups. The present cross-sectional study
      was conducted to obtain comprehensive information towards consumption of Targeted
      Fortified Products (TFP) among rural and urban mothers of children <3 years in
      Jaipur, India. METHODS: In this cross-sectional study conducted in 2012, three
      hundred rural and urban mothers were selected from Primary Health Centre, Achrol
      Village and Uniara Hospital in Jaipur, Rajasthan. The data were collected using a
      selfadministered questionnaire. The current nutritional status of children was
      determined by anthropometric measurements. RESULTS: A total of 53.33% rural and
      65.33% urban mothers had knowledge (P=0.046), amongst which 52.67% rural and
      66.00% urban mothers (P= 0.026) consumed TFP directed towards mothers. In
      addition, 56% rural and 94.67% urban mothers had knowledge (P=0.000) about TFP
      directed towards children, amongst which 19.33% rural and 50.67% urban mothers
      (P=0.000) fed their children with TFP. CONCLUSION: There was significantly less
      awareness regarding consumption of TFP directed towards both pregnant women and
      children among rural when compared to urban population. Attitudes seemed to be
      governed by the traditional beliefs and family influences of region rather than
      the knowledge obtained. There is a need of intensive coordinated efforts to
      create awareness among mothers to enhance the maternal and child diets through
      TFP.

PMID- 24688955
TI  - Correlation between Body Mass Index and Central Adiposity with Pregnancy
      Complications in Pregnant Women.
AB  - BACKGROUND: The prevalence of obesity is increasing throughout the world.Obesity
      assessed by body mass index (BMI) has shown to be associated with gestational
      complications while the relationship using waist circumference (WC) is not clear
      yet. The present study was aimed to determine the relationship between WC and
      adverse pregnancy complications. METHODS: In this prospective cohort study, 1140
      nulliparous pregnant women at 1st trimester of pregnancy referred to health care
      centers in Tabriz, Iran were enrolled in 2009-2010. Anthropometric indexes
      including (weight, height and WC) were measured using standardized measures and
      methods. BMI was classified into normal, overweight and obesity based on WHO
      classification. Abdominal obesity was defined as WC >= 88 cm. Pregnancy
      complication including gestational diabetes, hypertension and preeclamsia. Data
      were analyzed using SPSS, version 16. RESULTS: Mean of BMI and WC were 24.32+/
      4.08 kg/m(2), 81.84+/-9.25cm at 1(st) trimester of pregnancy, respectively.
      Prevalence of overweight (BMI=25-29.9kg/m(2)) and obesity (BMI>29.9 kg/m(2)) was
      27.6%, 8.8%, respectively. Abdominal obesity based on WC was 34.8%. Significant
      correlations were found between BMI and WC (r=0.73, P =0.0001). Women with
      BMI>29.9 kg/m(2) and WC>88 cm were more likely to suffer from gestational
      pregnancy and hypertension, as well as preeclampsia and preterm delivery.
      CONCLUSION: Early maternal WC similar to BMI is related with pregnancy
      complications.

PMID- 24688956
TI  - Coping Styles, Aggression and Interpersonal Conflicts among Depressed and Non
      Depressed People.
AB  - BACKGROUND: The present study compared people with depressive symptoms and people
      without depressive symptoms with reference to their coping styles, level of
      aggression and interpersonal conflicts. METHODS: A purposive sample of 128 people
      (64 depressed and 64 normal controls)was selected from four different teaching
      hospitals of Lahore. Both the groups were matched on four demographic levels i.e.
      age, gender, education and monthly income. Symptom Checklist-R was used to screen
      out depressed and non-depressed people. The Brief COPE, the Aggression
      Questionnaire and the Bergen Social Relationship Scale were used to assess coping
      styles, aggression and interpersonal conflicts respectively. The Independent t
      test was used to compare the groups. Binary logistic Regression was also carried
      out to predict the role of research variables in causing depression. RESULTS: The
      results showed that level of aggression and interpersonal conflict was
      significantly more in people with depressive symptoms as compared to control
      group. On the other hand control group was using more adaptive coping styles than
      people with depressive symptoms but no difference was found in the use of
      maladaptive coping styles. CONCLUSION: The present findings revealed that coping
      styles, aggression and interpersonal conflicts play important role in depression.
      Therefore, these dimensions must be considered while dealing with the depressive
      patients. Implications for preventive work are also discussed in the light of
      previous researches.

PMID- 24688957
TI  - Job Satisfaction Differences between Primary Health Care and Treatment Sectors:
      An Experience from Iran.
AB  - BACKGROUND: The aim of this study was to compare the levels of job satisfaction
      and its predictors among primary health care and treatment sectors' staff in East
      Azerbaijan Province, Iran. METHODS: This comparative study was conducted in East
      Azerbaijan Province,Iran in 2011. A questionnaire survey was performed on 420
      staff from health care and treatment sectors using multi-stage proportional
      cluster sampling method. Job satisfaction was measured in five aspects namely:
      structural and managerial; individual; social; work-itself; environmental and
      welfare job satisfaction factors.The job satisfaction measurement score was
      normalized to fall into a range of zero to 100. Statistical analyses were
      performed using Friedman and independent sample t-tests. RESULTS: Overall
      satisfaction in health and treatment sectors was moderate with a mean score above
      50. Hospital General Practitioners reported significantly higher job satisfaction
      score (mean +/- SD=57.34 +/- 17.02) compared to health care center General
      Practitioners (mean +/- SD= 31.74+/-14.99). The highest satisfaction scores
      belonged to individual factors both in health care sector staff (64.83+/-18.50)
      and treatment sector staff (63.55+/-17.44). The lowest job satisfaction was
      observed with environmental and welfare factors (38.47+/-19.86 and 36.83+/-19.86,
      respectively). CONCLUSION: The job satisfaction significantly differs between
      primary health care and treatment sectors. Based on the results, environmental
      and welfare factors may be targeted to improve the job satisfaction in public
      health care system.

PMID- 24688958
TI  - Challenging Ties between State and Tobacco Industry: Advocacy Lessons from India.
AB  - BACKGROUND: Globally, tobacco use is a major public health concern given its huge
      morbidity and mortality burden that is inequitably high in low- and middle-income
      countries. The World Health Organization has suggested banning the advertisement,
      promotion and sponsorship of tobacco. However, governments in some countries,
      including India, are either directly engaged in tobacco industry operations or
      have a mandate to promote tobacco industry development. This paper analyses a
      short-term advocacy campaign that challenged the state-tobacco industry ties to
      draw lessons for effective public health advocacy. METHOD: This paper uses a case
      study method to analyze advocacy efforts in India to thwart the state-tobacco
      industry partnership: the Indian government's sponsorship and support to a global
      tobacco industry event. The paper explores multiple strategies employed in the
      five-month advocacy campaign (May to October 2010) to challenge this state
      industry tie. In doing so, we describe the challenges faced and the lessons
      learnt for effective advocacy. RESULTS: Government withdrew participation and
      financial sponsorship from the tobacco industry event. Use of multiple strategies
      including engaging all concerned government agencies from the beginning,
      strategic use of media, presence and mobilization of civil society, and use of
      legal tools to gain information and judicial action, were complementary in
      bringing desired outcomes. CONCLUSION: Use of multiple and complementary advocacy
      strategies could lead to positive outcomes in a short-time campaign. The
      Framework Convention on Tobacco Control could form an important advocacy tool,
      especially in countries that have ratified it, to advocate for improvements in
      national tobacco control regulations.

PMID- 24688959
TI  - Environmental health problems and indicators in tabriz, iran.
AB  - BACKGROUND: Environmental Health Indicators (EHIs) are the most important
      criteria for evaluation of efficiency and effectiveness of the activities of the
      health sector. The operations and situation of the health system can be analyzed
      through surveying the indicators and comparing them during different times. The
      present study aimed to study the EHIs of Tabriz, using the common environmental
      health processes and national EHIs of the Ministry of Health. METHOD: The
      required information for determination of EHIs was collected from different
      sources, including mainly the Environmental Health Department of the Health
      Center of East Azerbaijan Province, Iran and other organizations. RESULTS: We
      found some important desirable and undesirable EHIs in Tabriz,including high
      percentage of households with access to safe and reliable drinking water, high
      safety in microbiological and chemical quality of drinking water, acceptable
      level of BOD5 and COD in the effluent of wastewater treatment plants (WTP), lack
      of complete municipal wastewater collection and treatment, relatively poor
      sanitation and health of food markets and public places, undesirable
      collection,transportation and disposal of municipal solid waste, low EHIs of some
      school classrooms, unacceptable disposal of medical waste in some hospitals, and
      finally high level of noise pollution in the city. CONCLUSION: Considering the
      poor condition of some EHIs of Tabriz, implementing proper actions for promotion
      of the indicators especially development of municipal wastewater collection,
      improvement of solid waste management,environmental health of some schools and
      mosques, and finally the noise pollution level of the city is recommended.

PMID- 24688960
TI  - Religiosity and Subjective Well-Being amongst Institutionalized Elderly in
      Pakistan.
AB  - BACKGROUND: In Pakistan, the issue of institutionalized elderly is a neglected
      area and little is known about their subjective conditions. The present study was
      conducted in 2012 which examined the relationship between religiosity and
      subjective well being amongst institutionalized elderly people. METHODS: Data was
      collected from 100 adults above the age of 60 years in Lahore,Pakistan, through
      purposive sampling strategy. Religiosity was measured through Religiosity Index,
      while Trait Well Being Inventory was used to assess subjective well being.
      RESULTS: Pearson product moment correlation coefficient and regression analysis
      were used for the analysis of the data, which revealed that religiosity has a
      significant positive relationship with life satisfaction. However, no association
      was found between religiosity and mood level. Moreover, regression analysis
      indicated that religiosity positively predicted life satisfaction among elderly.
      CONCLUSION: The current research would create awareness and urge the policy
      makers to look into this social issue and provide better long term care to the
      residents of old homes.

PMID- 24688962
TI  - Community based physiotherapy in India: an obscure profession?

PMID- 24688961
TI  - A comparison of selective classification methods in DNA microarray data of
      cancer: some recommendations for application in health promotion.
AB  - BACKGROUND: The aim of this study was to apply a new method for selecting a few
      genes, out of thousands, as plausible markers of a disease. METHODS: Hierarchical
      clustering technique was used along with Support Vector Machine (SVM) and Naive
      Bayes (NB) classifiers to select marker-genes of three types of breast cancer. In
      this method, at each step, one subject is left out and the algorithm iteratively
      selects some clusters of genes from the remainder of subjects and selects a
      representative gene from each cluster. Then, classifiers are constructed based on
      these genes and the accuracy of each classifier to predict the class of leftout
      subject is recorded. The classifier with higher precision is considered superior.
      RESULTS: Combining classification techniques with clustering method resulted in
      fewer genes with high degree of statistical precision. Although all classifiers
      selected a few genes from pre-determined highly ranked genes, the precision did
      not decrease. SVM precision was 100% with 22 genes instead of 50 genes while the
      NB resulted in higher precision of 97.95% in this case. When 20 highly ranked
      genes selected to be fed to the algorithm, same precision was obtained using 6
      and 5 genes with SVM and NB classifiers respectively. CONCLUSION: Using hybrid
      method could be effective in choosing fewer number of plausible marker genes so
      that the classification precision of these markers is increased. In addition,
      this method enables detecting new plausible markers that their association to
      disease under study is not biologically proved.

PMID- 24688963
TI  - A Group Intervention for HIV/STI Risk Reduction among Indian Couples.
AB  - BACKGROUND: HIV in India is transmitted primarily by heterosexual contact. The
      present study sought to test the feasibility of a group HIV/STI risk re-duction
      intervention among heterosexual couples in India. METHODS: Focus groups and key
      informant interviews were used in 2008 to cul-turally tailor the intervention.
      Thirty sexually active and HIV/STI negative cou-ples were enrolled and assessed
      regarding risk behavior and sexual barrier accept-ability. Gender-concordant
      group sessions used cognitive behavioral strategies for HIV/STI prevention.
      RESULTS: At baseline, male condom use was low (36%); no participants re-ported
      use of female condoms or vaginal gels. HIV knowledge was low; women had more HIV
      knowledge and more positive attitudes towards con-dom use than men. Post
      intervention, willingness to use all barrier products (t = 10.0, P< .001) and
      intentions to avoid risk behavior increased (t = 5.62, P< .001). CONCLUSION: This
      study illustrates the feasibility of utilizing a group interven-tion to enhance
      HIV/STI risk reduction among Indian couples.

PMID- 24688964
TI  - Weight management preferences in a non-treatment seeking sample.
AB  - BACKGROUND: Obesity is a serious public health issue in the United States, with
      the CDC reporting that most adult Americans are now either overweight or obese.
      Little is known about the comparative acceptability of available weight
      management approaches in non-treatment seeking samples. METHOD: This report
      presents preliminary survey data collected from an online sample on weight
      management preferences for 8 different weight management strategies including a
      proposed incentive-based program. Participants were 72 individuals (15 men, 55
      women and 2 transgendered individuals) who self-re-ported being overweight or
      obese, or who currently self-reported a normal weight but had attempted to lose
      weight in the past. RESULTS: ANOVA and Pair-wise comparison indicated clear
      preferences for cer-tain treatments over others in the full sample; most notably,
      the most popular option in our sample for managing weight was to diet and
      exercise without pro-fessional assistance. Several differences in preference
      between the three weight groups were also observed. CONCLUSIONS: Dieting and
      exercising without any professional assistance is the most highly endorsed weight
      management option among all groups. Overweight and obese individuals may find
      self-management strategies for weight loss less attractive than normal weight
      individuals, but still prefer it to other alternatives. This has implications for
      the development and dissemination of empirically based self-management strategies
      for weight.

PMID- 24688965
TI  - A focus group assessment to determine motivations, barriers and effectiveness of
      a university-based worksite wellness program.
AB  - BACKGROUND: This study explores university employee perceptions and under
      standing about its Worksite Health Promotion Program (WHPP). The WHPP included a
      Health Risk Appraisal (HRA), biometric screening, publicity for on-campus health
      programs and facilities, and health coaching. METHODS: A qualitative design was
      used based on a grounded theory ap-proach. Four 90 minutes focus groups with 6-8
      participants in each were conducted within a two 2 week period among employees,
      representing fac-ulty/participants, fac-ulty/nonparticipants, staff/participants,
      and staff/nonparticipants. Responses to questions about motivations, barriers,
      and perceived health benefits that impacted participation in the WHPP were digi
      tally recorded, transcribed and coded for themes. RESULTS: Incentives effectively
      motivated participation. Biometric screening had the largest impact on behavior
      change, followed by the information learned from the HRA. However, despite two
      thirds of the employees partici-pating in the pro-gram, lack of a full
      understanding of WHPP benefits and services lowered partici-pation in follow-up
      services and supplemental pro-grams. CONCLUSIONS: Biometric screening and HRAs
      effectively motivate program par-ticipation. Communication of benefits and
      services are important when providing WHPPs.

PMID- 24688966
TI  - Student's Body Dimensions in Relation to Classroom Furniture.
AB  - BACKGROUND: This study was carried out to investigate the fit between university
      student's anthropometry and classroom furniture dimensions. METHOD: In this cross
      sectional and descriptive-analyzing study conducted in 2012, a total of 194
      students (aged 18 through 30 years), were recruited randomly from Tabriz
      University of Medical Science community. The body size of each student was
      assessed using anthropometric measurements including shoulder height, elbow
      height, popliteal height, buttock-popliteal length, hip breadth and distance
      between elbows. Combinational equations defined the acceptable furni-ture
      dimensions according to anthropometry and match percentages were computed,
      according to either the existing situations assuming that they could use the most
      appropriate of the sizes available. RESULTS: Desk and seat height were higher
      than the accepted limits for most students (92.5% and 98.4%, respectively), while
      seat depth was appropriate for only 84.6% of students. The data indicate a
      mismatch between the students' bodily dimensions and the classroom furniture
      available to them. The chairs are too high and too deep and desks are also too
      high for the pupils. This situation may have negative effects on the sitting
      posture of the students especially when reading and writing. CONCLUSION: High
      mismatch percentages were found between furniture and stu-dents' anthropometry.
      The results confirm that furniture for university students should be selected and
      designed busied on their anthropometric dimensions.

PMID- 24688967
TI  - Recommendations for Tobacco Control on Post-Secondary Campuses that are
      Geographically Isolated.
AB  - BACKGROUND: Many Ontarians continue to report exposure to second-hand smoke in
      public spaces. Completely smoke-free environments are the preferred and socially
      responsible option for non-smoking policies; however, when considering the
      variety of landscapes in which post-secondary institutions are located, 'a one
      size fits all' smoking policy is unrealistic to implement and enforce. The
      purpose of the study was to: 1) gain a better sense of the prevalence of smoking
      and exposure to second-hand smoke in a post-secondary context that is
      geographically isolated; 2) assess the awareness of existing non-smoking
      initiatives; and 3) identify preferred approaches for tobacco control. METHODS:
      An online survey was distributed in 2012 to all members of the Laurentian
      University community. Descriptive statistics are presented, using frequency
      distributions, and group comparisons are reported, using Chi-Square analyses.
      RESULTS: A total of 1282 persons completed the survey. Nearly 80% of respondents
      reported that they had been exposed to second-hand smoke in the past month on
      campus and the majority of respondents felt that smoking should only be allowed
      in Designated Outdoor Smoking Areas (51.5%); including 37.3% of daily smokers and
      occasional smokers. CONCLUSION: Institutions with a geographically isolated
      campus, which limit options to divert smokers from public entrances, should
      consider the use of Designated Outdoor Smoking Areas. Implementation will create
      immediate reductions in the prevalence of smoking at building entrances and in
      high traffic locations and will therefore protect non-smokers from the dangers of
      environmental tobacco smoke.

PMID- 24688968
TI  - Heavy metals in the vegetables collected from production sites.
AB  - BACKGROUND: Contamination of vegetable crops (as an important part of people's
      diet) with heavy metals is a health concern. Therefore, monitoring levels of
      heavy metals in vegetables can provide useful information for promoting food
      safety. The present study was carried out in north-west of Iran (Tabriz) on the
      content of heavy metals in vegetable crops. METHODS: Samples of vegetables
      including kurrat (n=20) (Allium ampeloprasumssp. Persicum), onion (n=20) (Allium
      cepa) and tomato (n=18) (Lycopersiconesculentum var. esculentum), were collected
      from production sites in west of Tabriz and analyzed for presence of Cd, Cr, Cu,
      Ni, Pb and Zn by atomic absorption spectroscopy (AAS) after extraction by aqua
      regia method (drying, grounding and acid diges-tion). RESULTS: Mean +/- SD (mg/kg
      DW) concentrations of Cd, Cu, Cr, Ni and Zn were 0.32 +/- 0.58, 28.86 +/- 28.79,
      1.75 +/- 2.05, 6.37+/- 5.61 and 58.01 +/- 27.45, respec-tively. Cr, Cu and Zn
      were present in all the samples and the highest concentra-tions were observed in
      kurrat (leek). Levels of Cd, Cr and Cu were higher than the acceptable limits.
      There was significant difference in levels of Cr (P<0.05) and Zn (P<0.001) among
      the studied vegetables. Positive correlation was observed be-tween Cd:Cu
      (R=0.659, P<0.001) Cr:Ni (R=0.326, P<0.05) and Cr:Zn (R=0.308, P<0.05).  
      CONCLUSION: Level of heavy metals in some of the analyzed vegetables, especially
      kurrat samples, was higher than the standard levels. Considering the possi-ble
      health outcomes due to the consumption of contaminated vegetables, it is re
      quired to take proper actions for avoiding people's chronic exposure.

PMID- 24688969
TI  - Validity and Reliability of the Iranian Version of the HIV/AIDS Stigma Instrument
      PLWHA (HASI-P).
AB  - BACKGROUND: HIV/AIDS disease has remained highly stigmatized all over the world
      even though the increasing accessibility of its treatment. This study was
      designed to adapt the HIV/AIDS Stigma Instrument (HASI) to the Iranian People
      Living with HIV/AIDS (PLWHA). METHODS: Translation -back translation of the scale
      into Persian was done. Then, the validity and reliability of the instrument were
      evaluated. The validity of the translated scale was assessed in three ways:
      evaluating its linguistic validity, assessing its content validity by a panel of
      nine experts, and exploring its construct validity by factor analysis. The
      internal con-sistency of the translated scale was evaluated by Cronbach's Alpha.
      RESULTS: HASI showed a good Content Validity Index (CVI value >0.75) and Content
      Validity Ratio (CVR >0.78). The internal consistency of the instrument regarding
      the total score was alpha=0.89. The three stigma sub-scales that were dis-tancing
      and blaming (8 items, alpha=0.87), fear (3 items, alpha=0.82), and discrimination
      (5 items, alpha=0.83). CONCLUSION: This article reports the development and
      validation of a new measure of stigma, i.e. HIV/AIDS Stigma Instrument in PLWHA
      (HASI-P), and pro-vides evidence to support its content validity and internal
      consistency.

PMID- 24688970
TI  - Lipid profile in relation to anthropometric indices and insulin resistance in
      overweight women with polycystic ovary syndrome.
AB  - BACKGROUND: The present study was aimed to investigate lipid profile in relation
      to anthropometric indices and insulin resistance in overweight or obese women
      with polycystic ovary syndrome (PCOS). METHODS: In this cross-sectional study,
      lipid profile and anthropometric indices including body mass index (BMI), waist
      and hip circumference, waist to hip ratio (WHR), and waist to height ratio (WHtR)
      were evaluated in 63 overweight or obese PCOS patients subdivided into insulin
      resistant (IR) and non insulin-resistant (NIR) groups. IR was defined as
      homeostasis model of insulin resistance (HOMA-IR) >=3.8. RESULTS: Fasting insulin
      concentration and HOMA-IR were higher (P<0.001) and high-density lipoprotein
      cholesterol (P=0.012) was lower in IR group. All of the anthropometric measures
      other than WHR and BMI showed significant correlations with several lipid
      parameters. Amongst, WHtR showed the strongest correlation with total cholesterol
      (TC) (r=0.37; P=0.004) and low density lipoprotein cholesterol (LDL-C) (r=0.33;
      P=0.011) in the whole PCOS patients. CONCLUSION: Anthropometric characteristics
      (especially BMI and hip circum-ference) are more important parameters correlated
      to lipid profile than IR in overweight or obesePCOS patients, confirming the
      importance of early treat-ment of obesity to prevent dyslipidemia in the future.

PMID- 24688971
TI  - Functional status, anxiety, cardiac self-efficacy, and health beliefs of patients
      with coronary heart disease.
AB  - BACKGROUND: Beliefs and emotions could effect on functional status, quality of
      life, and mortality amongst patients who are suffering coronary heart disease
      (CHD). Current study examined the role of anxiety: trait/ state, self-efficacy,
      health beliefs, and functional status among patient with history of CHD. METHOD:
      In this correlational study, 105 hospitalized and outpatients patients suffering
      CHD in Tehran Heart Center Hospital participated by using convenience sampling
      method in 2012. Cardiac self-efficacy, Seattle Angina, and research-designed
      health beliefs questionnaires were used to gather data. RESULTS: The functional
      status in CHD patients showed significant relationships with gender, job, and
      type of medical insurance of the participants (All ps<0.05). In addition ,
      perceived vulnerability to face again cardiac attack in the future, per-ceived
      severity of next cardiac attack, anxiety, state anxiety and trait anxiety (All
      ps<0.05) had significant and negative relationships with functional status. Con
      versely, the cardiac self-efficacy had a positive and significant relationship
      (P<0.001) with functional status. CONCLUSION: Psychological factors have
      important role in functional status and quality of life of patients who suffering
      CHD. Therefore, it is necessary to emphasize on supportive and complementary
      programs to promote Cardiac Reha-bilita-tion Programs.

PMID- 24688972
TI  - Open groups: adaptations in implementing a parent training program.
AB  - BACKGROUND: Programs that focus on positive parenting have been shown to improve
      parental attitudes, knowledge, and behaviors, and increase parent and child
      bonding. These programs are typically conducted in a closed group for-mat.
      However, when individual or community needs are more immediate, programmers
      sometimes opt for an open group format. To determine the effectiveness of this
      adaptation to an open group format, the present study compared both groups on
      parental out-comes. METHODS: Both closed and open group formats were offered and
      implemented between January 2009 and December 2012. Participants for both formats
      were recruited through similar means and the format placement for each family was
      determined by the immediacy of the need for an intervention, the time lapse until
      a new cycle would begin, and scheduling flexibility. Chi-Square analyses were
      conducted to determine demographic differences between the two groups and gain
      scores were calculated from the pre- and post-test AAPI-2 scales within a mixed
      MANOVA to determine group format effectiveness. RESULTS: Though open groups
      contained higher risk families; parental outcome improvements were significant
      for both groups. All participants, regardless of group membership, demonstrated
      the same statistically significant improvements following completion of the
      program. CONCLUSION: Findings provide support for adapting group formats when
      necessary to fit community and individual needs.

PMID- 24688973
TI  - The effect of zinc supplementation of lactating rats on short-term and long-term
      memory of their male offspring.
AB  - BACKGROUND: In this study the effect of zinc chloride (ZnCl2) administration on
      the short-term and long-term memory of rats were assessed. METHODS: We enrolled
      six groups of adult female and control group of eight Wistar rats in each group.
      One group was control group with free access to food and water, and five groups
      drunk zinc chloride in different doses (20, 30, 50, 70 and 100 mg/kg/day) in
      drinking water for two weeks during lactation .One month after birth, a shuttle
      box used to short- term and long-term memory and the latency in entering the dark
      chamber as well. RESULTS: This experiment showed that maternal 70 mg/kg dietary
      zinc during lactation influenced the working memory of rats' offspring in all
      groups. Rats received 100 mg/kg/day zinc during lactation so they had significant
      impairment in working memory (short-term) of their offspring (P<0.05). There was
      no significant difference in reference (long-term) memory of all groups.
      CONCLUSION: Drug consumption below70 mg/kg/day zinc chloride during lactation had
      no effect. While enhanced 100 mg/ kg/ day zinc in lactating rats could cause
      short-term memory impairment.

PMID- 24688974
TI  - Correlates of willingness to engage in residential gardening: implications for
      health optimization in ibadan, Nigeria.
AB  - BACKGROUND: Gardening is a worthwhile adventure which engenders health op
      timization. Yet, a dearth of evidences that highlights motivations to engage in
      gardening exists. This study examined willingness to engage in gardening and its
      correlates, including some socio-psychological, health related and socio
      demographic variables. METHODS: In this cross-sectional survey, 508 copies of a
      structured questionnaire were randomly self administered among a group of civil
      servants of Oyo State, Nigeria. Multi-item measures were used to assess
      variables. Step wise multiple regression analysis was used to identify predictors
      of willingness to engage in gar-dening Results: Simple percentile analysis shows
      that 71.1% of respondents do not own a garden. Results of step wise multiple
      regression analysis indicate that descriptive norm of gardening is a good
      predictor, social support for gardening is better while gardening self efficacy
      is the best predictor of willingness to engage in gardening (P< 0.001). Health
      consciousness, gardening response efficacy, education and age are not predictors
      of this willingness (P> 0.05). Results of t-test and ANOVA respectively shows
      that gender is not associated with this willingness (P> 0.05), but marital status
      is (P< 0.05).  CONCLUSION: Socio-psychological characteristics and being married
      are very rele-vant in motivations to engage in gardening. The nexus between
      gardening and health optimization appears to be highly obscured in this
      population.

PMID- 24688975
TI  - Stress and Nutritional Status of Individuals in Uttarakhand, North-ern India:
      Differential Effect of Gender.
AB  - BACKGROUND: Uttarakhand, Northern India is facing challenges in the issues
      concerning public health. Hence, researches identifying the stressors and nutri
      tional factors influencing health are encouraged. This study attempts to assess
      the stress levels and nutritional status. Gender differences are also measured in
      the same. METHODS: Stress and nutritional status related information was gathered
      (Nov, 2012-June, 2013) from 118 individuals residing in Uttarakhand state. Stress
      level was assessed using Personal Stress Score Inventory. Anthropo-metric details
      and dietary intake (3 day food recall method) were collected. Nutrient intake
      were calculated and compared with recommended dietary allowance (RDA) for Indi
      ans. T-test and Chi-square (chi2) were performed to measure the gender difference
      in studied variables. RESULTS: 66.6% of females and 85.4% of males reported
      moderate stress (31-79). Males were seen to be more stressed then females, though
      no sig-nificant differ-ence was seen. A significant difference in BMI (Body mass
      Index) was seen be-tween males (24.1 kg/m(2)) and females (21.5 kg/m(2)). The
      study sample was found to be deficient in iron and zinc when compared with RDA.
      Females suf-fering from various level of stress had significantly lower levels of
      energy, pro-tein, zinc than males. CONCLUSION: Majority of subjects were
      suffering from moderate level of stress. The anthropometric status of subjects
      was good, though females showed signifi-cantly lower intake of nutrients compared
      to men. Poor intake of iron and zinc points towards a possibility of hidden
      hunger. Hence, psy-chological and nutri-tional counseling may be required.

PMID- 24688976
TI  - Early Warning System for Disasters within Health Organizations: A Mandatory
      System for Developing Countries.
AB  - BACKGROUND: Disaster identification and alert systems can be processed in dif
      ferent ways. An early warning system is designed to detect impending danger and
      send appropriate and clear signals to at risk communities and organizations at
      the right time and in an unambiguous way. This study aimed to determine early
      warning system for disaster within health organization in Iran. METHODS: This
      article presents the findings of a mixed-methods study of early warning systems
      for disaster management within the health organizations in Iran. During the years
      2011 to 2012, a sample of 230 health managers was surveyed using a questionnaire
      and 65 semi-structured interviews were conducted with public health and
      therapeutic affairs managers who were responsible for disaster management.
      RESULTS: A range of problems were identified. Although there is a multi-agency
      alert system within the health organizations, other indicators of early warning
      system are not satisfactory. Furthermore, standard messages which are used to
      alert organizations are not used under the current system. CONCLUSION: Some
      activities such as memorandum of understanding among different stakeholders of
      disaster response and education of staff and communities could improve the
      response to disasters within the health organizations.

PMID- 24688977
TI  - Predicting Aggression among Male Adolescents: an Application of the Theory of
      Planned Behavior.
AB  - BACKGROUND: Aggressive behaviorin adolescencecan be expressed asa predictorfor
      crime, substanceabuse, depression and academic failure. The purpose of this study
      was to determine the prediction of aggression among Iranian adolescent based on
      theory of planned behavior (TPB) as a theoretical framework. METHODS: In this
      cross-sectional study, conducted in Yasuj County, south of Iran, during 2011, a
      total of 256 male adolescents, were randomly enrolled. Participants filled out a
      self-administered questionnaire. Data were analyzed by SPSS version 21 using
      bivariate correlations, and linear regression statistical tests at 95% signifi
      cant level. RESULT: The three predictor variables of 1) attitude, 2) subjective
      norms, and 3) perceived behavioral control, accounted for 40% of the variation in
      the outcome measure of the aggression intention. Besides, intention accounted for
      15% of the variation in the outcome measure of the aggression behavior. There was
      a sig-nificant correlation between drug abuse and alcohol consumption, have
      friend drug user, unprotect sex and parents divorced with aggression (P< 0.05).
      CONCLUSIONS: Designing intervention to reduction positive attitude and subjective
      norms toward aggressive behavior among adolescents could be usefulness result to
      aggression prevention.

PMID- 24688978
TI  - Advantages and disadvantages of different methods of hospitals' downsizing: a
      narrative systematic review.
AB  - BACKGROUND: Hospitals as key actors in health systems face growing pres-sures
      especially cost cutting and search for costeffective ways to resources
      management. Downsizing is one of these ways. This study was conducted to identify
      advantages and disadvantages of different methods of hospital' downsizing.
      METHODS: The search was conducted in databases of Medlib, SID, Pub Med, Science
      Direct and Google Scholar Meta search engine by keywords of Downsizing, Hospital
      Downsizing, Hospital Rightsizing, Hospital Restructuring, Staff Downsizing,
      Hospital Merging, Hospital Reorganization and the Persian equivalents. Resulted
      815 articles were studied and refined step by step. Finally, 27 articles were
      selected for analysis. RESULTS: Five hospital downsizing methods were identified
      during searching. These methods were reducing the number of employees and beds,
      outsourcing, integration of hospital units, and the combination of these methods.
      The most important benefits were cost reduction, increasing patient satisfaction,
      increasing home care and outpatient services. The most important disadvantage
      included reducing access, reducing the rate of hospital admissions and increasing
      employees' workload and dissatisfaction. CONCLUSION: Each downsizing method has
      strengths and weaknesses. Using different methods of downsizing, according to
      circumstances and applying appropriate interventions after implementation, is
      necessary for promotion.

PMID- 24688979
TI  - Assessment of Nutritional and Depression Status in Free-Living El-derly in
      Tabriz, Northwest Iran.
AB  - BACKGROUND: Malnutrition and depression are the common health problems in elderly
      population. Poor nutrition might have a strong effect on the incidence of
      depression. The aims of this study were to assess the nutritional and depression
      status and the possibly relationship between these variables in the urban free
      liv-ing elderly in Tabriz, northwestern Iran. METHODS: This cross-sectional study
      was carried out on 184 elderly people (male=97; female=87) with age 60 years or
      elder in 2012. All subjects entered to the study voluntarily from those attending
      to daily care centers for elderly peo-ple. Mini Nutritional Assessment (MNA) tool
      and Geriatric Depression Score (GDS) were used to evaluate nutritional status and
      depression scores, respec-tively. Con-tinuous variables were expressed as mean +/
      standard deviation (SD) and qualita-tive data were presented as frequency
      (percent). Spearman's correla-tion was em-ployed to determine the relationship
      between variables. RESULTS: Up to 50% of subjects had poor nutrition status.
      About 14% of elderly people had serve depression and 28.3% had mild depression.
      There was a posi-tive significant correlation between MNA and GDS tests in both
      gender (r=0.416; P<0.001). CONCLUSION: There was no acceptable level of
      nutritional status and mental health in the elderly people. Further studies are
      needed to evaluate the other factors that can effect on the quality of life in
      this population.

PMID- 24688980
TI  - A Simple Scalable Association Hypothesis Test Combining Gene-wide Evidence From
      Multiple Polymorphisms.
AB  - AIMS: In single-nucleotide polymorphism (SNP) scans, SNP-phenotype association
      hypotheses are tested, however there is biological interpretation only for genes
      that span multiple SNPs. We demonstrate and validate a method of combining gene
      wide evidence using data for high-density lipoprotein cholesterol (HDLC).
      METHODOLOGY: In a family based study (N=1782 from 482 families), we used 1000
      phenotype-permuted datasets to determine the correlation of z-test statistics for
      592 SNP-HDLC association tests comprising 14 genes previously reported to be
      associated with HDLC. We generated gene-wide p-values using the distribution of
      the sum of correlated z-statistics. RESULTS: Of the 14 genes, CETP was
      significant (p=4.0*10-5 <0.05/14), while PLTP was significant at the borderline
      (p=6.7*10-3 <0.1/14). These p-values were confirmed using empirical distributions
      of the sum of chi2 association statistics as a gold standard (2.9*10-6 and 1.8*10
      3, respectively). Genewide p-values were more significant than Bonferroni
      corrected p-value for the most significant SNP in 11 of 14 genes (p=0.023).
      Genewide p-values calculated from SNP correlations derived for 20 simulated
      normally distributed phenotypes reproduced those derived from the 1000 phenotype
      permuted datasets were correlated with the empirical distributions (Spearman
      correlation = 0.92 for both). CONCLUSION: We have validated a simple scalable
      method to combine polymorphism-level evidence into gene-wide statistical
      evidence. High-throughput gene-wide hypothesis tests may be used in biologically
      interpretable genomewide association scans. Genewide association tests may be
      used to meaningfully replicate findings in populations with different linkage
      disequilibrium structure, when SNP-level replication is not expected.

PMID- 24688981
TI  - Hospitalization of children with down syndrome.
AB  - INTRODUCTION: Children with Down syndrome present with multiple medical problems
      in a higher prevalence compared with the general population, which may lead to
      hospitalizations. METHODS: Analysis of 560 hospitalizations of 162 children aged
      0-16 years with Down syndrome at Hadassah Medical Center during the years 1988
      2007 compared with data on children in the general population, hospitalized at
      the same period. Data was collected from patient files and statistical data from
      the Ministry of Health. RESULTS: Respiratory infections were the leading cause
      for hospitalization of children with Down syndrome. The number of
      hospitalizations of children with Down syndrome compared to the number of all
      children, who were hospitalized was surprisingly similar to their proportion in
      the general population. Eleven children died during their hospitalization (five
      heart failure, three sepsis, one respiratory tract infection, and one due to
      complication after surgery). Nine of the 11 had a congenital heart anomaly.
      CONCLUSION: Children with Down syndrome can present with complex medical issues
      and we support the concept of a multidisciplinary team that has experience and
      knowledge to serve as a "one stop shop" for these individuals and their families,
      with timely visits in which a comprehensive evaluation is performed, problems
      attended to and prevention plans applied. In this way, we may prevent morbidity,
      hospitalizations, and mortality.

PMID- 24688982
TI  - Editors' page.

PMID- 24688983
TI  - Majnoon lila.
AB  - SUMMARY: The love story of Majnoon Lila is well known across all levels of
      society in the Arab world. The story is famous in Arabic literature as well as in
      Arab folk stories. In this paper, the poems of Quasis are analyzed and a
      diagnosis of organic heart failure is made from his complaints.

PMID- 24688984
TI  - ALDO-DHF & Paramount.

PMID- 24688985
TI  - FAME 2 - The best initial strategy for patients with stable coronary artery
      disease: Do we have an answer at last?

PMID- 24688986
TI  - PCI versus CABG in patients with complex coronary artery disease: Time for
      reconciliation?

PMID- 24688987
TI  - CABG in 2012: Evidence, practice and the evolution of guidelines.
AB  - In the management of coronary artery disease (CAD) it is important to ensure that
      all patients are receiving optimal medical therapy irrespective of whether any
      intervention, by stents or surgery, is planned. Furthermore it is important to
      establish if a proposed intervention is for symptomatic and/or prognostic
      reasons. The latter can only be justified if there is demonstration of a
      significant volume of ischaemia (>10% of myocardial mass). Taking together
      evidence from the most definitive randomized trial and its registry component
      (SYNTAX), almost 79% of patients with three vessel CAD and almost two thirds of
      patients with LMS disease have a survival benefit and marked reduction in the
      need for repeat revascularisation with CABG in comparison to stents, implying
      that CABG is still the treatment of choice for most of these patients. This
      conclusion which is apparently at odds with the results of most previous trials
      of stenting and surgery but entirely consistent with the findings of large
      propensity matched registries can be explained by the fact that SYNTAX enrolled
      'real life' patients rather than the highly select patients usually enrolled in
      previous trials. SYNTAX also shows that for patients with less severe coronary
      artery disease there is no difference in survival between CABG and stents but a
      lower incidence of repeat revascularisation with CABG. At three years, SYNTAX
      shows no difference in stroke between CABG and stents for three-vessel disease
      but a higher incidence of stroke with CABG in patients with left main stem
      disease. In contrast the PRECOMBAT trial of stents and CABG in patients with left
      main stem disease showed no excess of mortality or stroke with CABG in comparison
      to stents in relatively low risk patients. Finally the importance of guidelines
      and multidisciplinary/heart teams in making recommendations for interventions is
      emphasised. 

PMID- 24688988
TI  - Guidelines for revascularization: The evidence base matures.

PMID- 24688989
TI  - Primary angioplasty in Europe: From trials to practice.
AB  - This manuscript is focused around two key messages from the current Guidelines of
      the European Society of Cardiology on ST elevation myocardial infarction; the
      need to use primary angioplasty whenever timely and effectively applicable and
      the importance of organisational changes in the emergency system to implement
      this indication. Based on a review of the trials motivating these guidelines and
      the successful experience of many European countries, practical indications are
      provided on the methods to overcome resistances and malpractices that prevent the
      delivery of optimal care in these critically ill patients. 

PMID- 24688990
TI  - Primary coronary angioplasty for ST-Elevation Myocardial Infarction in Qatar:
      First nationwide program.
AB  - In this article, we outline the plans, protocols and strategies to set up the
      first nationwide primary Percutaneous Coronary Intervention (PCI) program for ST
      elevation myocardial Infarction (STEMI) in Qatar, as well as the difficulties and
      the multi-disciplinary solutions that we adopted in preparation. We will also
      report some of the landmark literature that guided our plans. The guidelines
      underscore the need for adequate number of procedures to justify establishing a
      primary-PCI service and maintain competency. The number of both diagnostic and
      interventional procedures in our centre has increased substantially over the
      years. The number of diagnostic procedures has increased from 1470 in 2007, to
      2200 in 2009 and is projected to exceed 3000 by the end of 2012. The total number
      of PCIs has also increased from 443 in 2007, to 646 in 2009 and 1176 in 2011 and
      is expected to exceed 1400 by the end of 2012. These figures qualify our centre
      to be classified as 'high volume', both for the institution and for the
      individual interventional operators. The initial number of expected primary PCI
      procedures will be in excess of 600 procedures per year. Guidelines also
      emphasize the door to balloon time (DBT), which should not exceed 90 minutes.
      This interval mainly represents in-hospital delay and reflects the efficiency of
      the hospital system in the rapid recognition and transfer of the STEMI patient to
      the catheterization laboratory for primary-PCI. Although DBT is clearly important
      and is in the forefront of planning for the wide primary PCI program, it is not
      the only important time interval. Myocardial necrosis begins before the patient
      arrives to the hospital and even before first medical contact, so time is of the
      essence. Therefore, our primary PCI program includes a nationwide awareness
      program for both the population and health care professionals to reduce the pre
      hospital delay. We have also taken steps to improve the pre-hospital diagnosis of
      STEMI. In addition to equipping all ambulances to perform 12-lead
      electrocardiograms (ECGs) we will establish advanced wireless transmission of the
      ECG to our Heart Centre and to the smart phone of the consultant on-call for the
      primary-PCI service. This will ensure that the patient is transferred directly to
      the cath lab without unnecessary delay in the emergency rooms. A single phone
      call system will allow the first medic making the diagnosis to activate the
      primary PCI team. The emergency medical system is acquiring capability to track
      the exact position of each ambulance using GPS technology to give an accurate
      estimate of the time needed to arrive to the patient and/or to the hospital. We
      also plan for medical helicopter evacuation from remote or inaccessible areas. A
      comprehensive research database is being established to enable specific
      pioneering research projects and clinical trials, either as a single centre or in
      collaboration with other regional or international centers. The primary-PCI
      program is a collaborative effort between the Heart Hospital, Hamada Medical
      Corporation and the Qatar Cardiovascular Research Centre, a member of Qatar
      Foundation. Qatar will be first country to have a unified nationwide primary-PCI
      program. This clinical and research program could be a model that may be adopted
      in other countries to improve outcomes of patients with STEMI. 

PMID- 24688991
TI  - Study exploring depression and cardiovascular diseases amongst Arabic speaking
      patients living in the State of Qatar: Rationale and methodology.
AB  - In Qatar, cardiovascular diseases are the leading cause of death. Studies show
      that depression is associated with an increased morbidity and mortality among
      cardiovascular patients. Thus, early detection of, and intervention for,
      depression among cardiovascular patients can reduce cardiovascular morbidity and
      mortality, and save health care costs. To date there is no study in the Gulf
      region exploring depression among cardiovascular patients. The goals of our three
      phase research program are to (1) understand the mental health issues,
      specifically depression, as experienced by cardiovascular patients living in the
      State of Qatar; (2) identify and implement strategies that would prevent
      depression and assist patients to deal with depression; and (3) evaluate,
      facilitate, and sustain strategies that are effective at reducing depression and
      foster its treatment among cardiovascular patients. This paper describe phase I
      of the research program. Using both quantitative and qualitative research
      methodologies, we will investigate (1) the prevalence and severity of depression
      among patients who have confirmed diagnosis of cardiovascular diseases (2) how
      contextual factors such as social, cultural, and economic factors contribute to
      the risk of depression and its management among cardiovascular patients, and (3)
      formulate effective intervention strategies that are expected to increase
      awareness, prevention of and treatment for depression among cardiovascular
      patients, thus reducing cardiovascular diseases morbidity and mortality in Qatar.

PMID- 24688992
TI  - Changes in left atrial deformation in hypertrophic cardiomyopathy: Evaluation by
      vector velocity imaging.
AB  - OBJECTIVES: Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic
      process affecting both ventricular and atrial myocardium. We assessed the global
      and regional left atrial (LA) function and its relation to left ventricular (LV)
      mechanics and clinical status in patients with HCM using Vector Velocity Imaging
      (VVI). METHODS: VVI of the LA and LV was acquired from apical four- and two
      chamber views of 108 HCM patients (age 40 +/- 19years, 56.5% men) and 33 healthy
      subjects, all had normal LV systolic function. The LA subendocardium was traced
      to obtain atrial volumes, ejection fraction, velocities, and strain
      (epsilon)/strain rate (SR) measurements. RESULTS: Left atrial reservoir
      (epsilonsys,SRsys) and conduit (early diastolic SRe) function were significantly
      reduced in HCM compared to controls (P < .0001). Left atrial deformation directly
      correlated to LVepsilonsys, SRsys and negatively correlated to age, NYHA class,
      left ventricular outflow tract (LVOT) gradient, left ventricular mass index
      (LVMI), LA volume index and severity of mitral regurge (P < 0.001). Receiver
      operating characterist was constructed to explore the cutoff value of LA
      deformation in differentiation of LA dysfunction; epsilonsys < 40% was 75%
      sensitive, 50% specific, SRsys < 1.7s(- 1) was 70% sensitive, 61% specific, SRe> 
      1.8s(- 1) was 81% sensitive and 30% specific, SRa> - 1.5s(- 1) was 73% sensitive
      and 40% specific. By multivariate analysis global LVepsilonsys and LV septal
      thickness are independent predictors for LAepsilonsys, while end systolic
      diameter is the only independent predictor for SRsys, P < .001. CONCLUSION: Left
      atrial reservoir and conduit function as measured by VVI were significantly
      impaired while contractile function was preserved among HCM patients. Left atrial
      deformation was greatly influenced by LV mechanics and correlated to severity of
      phenotype.

PMID- 24688993
TI  - A global perspective of arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited
      heart disease characterized by ventricular arrhythmias and sudden cardiac death
      especially in the young. ARVC has been traditionally associated with the
      Mediterranean basin, as many seminal studies on the disease have originated from
      research groups of this region. Today, however, numerous ARVC registries from all
      over the world emphasize that the disease does not have a specific racial or
      geographical predilection. This work provides a review on the global perspective
      of ARVC. 

PMID- 24688994
TI  - Robotic excision of aortic valve papillary fibroelastoma and concomitant maze
      procedure.
AB  - Cardiothoracic surgeons have utilized the surgical robot to provide a minimally
      invasive approach to a number of intracardiac operations, including tumor
      resection, valve repair, and ablation of atrial arrhythmia. We report the case of
      a 58 year-old woman who was found to have a mobile mass on her aortic valve
      during evaluation of atrial fibrillation. Both of these conditions were addressed
      when she underwent a combined robotic biatrial Maze procedure and excision of the
      mass, which proved to be a papillary fibroelastoma of the aortic valve. 

PMID- 24688995
TI  - Editors' page.

PMID- 24688996
TI  - Acute coronary syndrome in the Middle East: The importance of registries for
      quality assessment and plans for improvement.
AB  - Acute coronary syndrome (ACS) represents one of the most common causes of death
      worldwide. Several practice guidelines have been developed in Europe and North
      America to improve outcome of ACS patients through implementation of the
      recommendations into clinical practice. It is well know that there is wide gap
      between guidelines and implementation in real practice as was demonstrated in
      registry findings mainly conducted in the developed world. Here in we review main
      gaps in the management of ACS patients observed from two recent registries
      conducted in the Middle East. 

PMID- 24688997
TI  - CADUCEUS, SCIPIO, ALCADIA: Cell therapy trials using cardiac-derived cells for
      patients with post myocardial infarction LV dysfunction, still evolving.

PMID- 24688999
TI  - Bioengineering and the cardiovascular system.
AB  - The development of the modern era of bioengineering and the advances in our
      understanding of the cardiovascular system have been intertwined over the past
      one-half century. This is true of bioengineering as an area for research in
      universities. Bioengineering is ultimately the beginning of a new engineering
      discipline, as well as a new discipline in the medical device industry. 

PMID- 24689000
TI  - Self-Assembled Metal-Organic Polyhedra (MOPs): Opportunities in Biomedical
      Applications.
AB  - Self-assembly is a powerful synthetic tool that has enabled chemists to construct
      numerous, structurally complex, supermolecules of various shapes, functionality,
      and dimensions from relatively simple precursors. Metal-organic polyhedra (MOPs)
      are an emerging family of self-assembled supermolecules that have intriguing
      structures and tailored functionality. During the last decade, research in this
      area have rapidly evolved and interest is now directed towards fine tuning and
      tailoring such structures targeting applications in sensing, catalysis, and most
      recently, in the biomedical field. Three examples of MOPs of interest showing
      promising potentials for biomedical applications are described. 

PMID- 24688998
TI  - The zebrafish model system in cardiovascular research: A tiny fish with mighty
      prospects.

PMID- 24689003
TI  - Letter by Elshazly Regarding Article "Primary Coronary Angioplasty for ST
      Elevation Myocardial Infarction (STEMI) in Qatar: First Nationwide Program".

PMID- 24689001
TI  - Temperature management in cardiac surgery.

PMID- 24689002
TI  - Science and practice of arrhythmogenic cardiomyopathy: A paradigm shift.

PMID- 24689004
TI  - An electronic medical record-linked biorepository to identify novel biomarkers
      for atherosclerotic cardiovascular disease.
AB  - BACKGROUND: Atherosclerotic vascular disease (AVD), a leading cause of morbidity
      and mortality, is increasing in prevalence in the developing world. We describe
      an approach to establish a biorepository linked to medical records with the
      eventual goal of facilitating discovery of biomarkers for AVD. METHODS: The
      Vascular Disease Biorepository at Mayo Clinic was established to archive DNA,
      plasma, and serum from patients with suspected AVD. AVD phenotypes, relevant risk
      factors and comorbid conditions were ascertained by electronic medical record
      (EMR)-based electronic algorithms that included diagnosis and procedure codes,
      laboratory data and text searches to ascertain medication use. RESULTS: Up to
      December 2012, 8800 patients referred for vascular ultrasound examination and non
      invasive lower extremity arterial evaluation were approached, of whom 5268
      consented. The mean age of the initial 2182 patients recruited was 70.4 +/- 11.2
      years, 62.6% were men and 97.6% were whites. The prevalences of AVD phenotypes
      were: carotid artery stenosis 48%, abdominal aortic aneurysm 21% and peripheral
      arterial disease 38%. Positive predictive values for electronic phenotyping
      algorithms were>0.90 for cases (and>0.95 for controls) for each AVD phenotype,
      using manual review of the EMR as the gold standard. The prevalences of risk
      factors and comorbidities were as follows: hypertension 78%, diabetes 29%,
      dyslipidemia 73%, smoking 70%, coronary heart disease 37%, heart failure 12%,
      cerebrovascular disease 20% and chronic kidney disease 19%. CONCLUSIONS: Our
      study demonstrates the feasibility of establishing a biorepository of plasma,
      serum and DNA, with relatively rapid annotation of clinical variables using EMR
      based algorithms.

PMID- 24689005
TI  - Further insights into the syndrome of prolapsing non-coronary aortic cusp and
      ventricular septal defect.
AB  - Ventricular septal defect (VSD) with prolapse of the right coronary cusp and
      aortic regurgitation can be managed surgically with the anatomical correction
      technique. However when the VSD is located underneath the non coronary cusp
      surgical management differs due to anatomical constraints and secondary
      pathological changes seen in the non coronary cusp. It is therefore important
      that the location of the VSD and the morphology of prolapsing cusp be
      characterised preoperatively in order to plan appropriate surgical repair. We
      present a case study in which we discuss the salient differences in the surgical
      management of the prolapsing right and the prolapsing non coronary cusps. 

PMID- 24689006
TI  - Response to the letter of Elshazly.

PMID- 24689008
TI  - Editors' page.

PMID- 24689009
TI  - Global Burden of Disease 2010 Study: A personal reflection.

PMID- 24689007
TI  - Peripheral arterial disease in the Middle East: Underestimated predictor of worse
      outcome.
AB  - Peripheral arterial disease (PAD) is a common manifestation of systemic
      atherosclerosis and is associated with significant morbidity and mortality. The
      prevalence of PAD in the developed world is approximately 12% among adult
      population, which is age-dependent and with men being affected slightly more than
      women. Despite the strikingly high prevalence of PAD, the disease is
      underdiagnosed. Surprisingly, more than 70% of primary health care providers in
      the US were unaware of the presence of PAD in their patients. The clinical
      presentation of PAD may vary from asymptomatic to intermittent claudication,
      atypical leg pain, rest pain, ischemic ulcers, or gangrene. Claudication is the
      typical symptomatic expression of PAD. However, the disease may remains
      asymptomatic in up to 50% of all PAD patients. PAD has also been reported as a
      marker of poor outcome among patients with coronary artery disease. Despite the
      fact that the prevalence of atherosclerotic disease is increasing in the Middle
      East with increasing cardiovascular risk factors (tobacco use, diabetes mellitus
      and the metabolic syndrome), data regarding PAD incidence in the Middle East are
      scarce. 

PMID- 24689010
TI  - The RIME trial: Are we closer to the answer of when to repair ischemic mitral
      regurgitation?

PMID- 24689011
TI  - ARCTIC: Additional proof against antiplatelet adjusted therapy.

PMID- 24689012
TI  - TRIOLOGY ACS: No benefit/No harm.

PMID- 24689013
TI  - The Boy from Fez: A tale of five charities, and the global community, joining
      hands.
AB  - A case study in global cooperation between multiple charities and cardiac centers
      helped to save a 8-year-old Moroccan boy suffering a case of Laubry-Pezzi
      syndrome with severe aortic regurgitation and ventricular septal defect. His
      recuperation was aided by the support of communities in both Morocco and Qatar. 

PMID- 24689014
TI  - Advanced ablation strategies for management of post-surgical atrial arrhythmias.
AB  - Post-surgical arrhythmias include a wide range of arrhythmias occurring late
      after cardiac surgery and represent a complex substrate for catheter ablation
      either because of extended scar and remodeling or because of limited access to
      the area of interest. Novel image integration and ablation tools have made the
      catheter ablation in this population both feasible and successful. We review a
      structured approach to catheter ablation of post-surgical atrial arrhythmias in
      various patient cohorts including the most common congenital heart defects. 

PMID- 24689015
TI  - Origin and development of modern medicine at the University of Padua and the role
      of the "Serenissima" Republic of Venice.

PMID- 24689016
TI  - Apical ballooning with mid-ventricular obstruction: the many faces of Takotsubo
      cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TTC) is a transient left ventricular dysfunction due to
      akinesia of the left-ventricular (LV) mid-apical segments (apical ballooning),
      which can cause severe reduction in LV systolic function. The typical clinical
      picture of TTC include chest pain, electrocardiographic changes consisting of
      mild ST-segment elevation followed by diffuse deep T-wave inversion, QTc interval
      prolongation and mild troponin release in the absence of significant coronary
      stenoses. The syndrome often affects post-menopausal women and is triggered by
      sympathetic overstimulation, like intense physical or emotional stress, so that
      it is called the "broken heart syndrome". Although left-ventricular systolic
      dysfunction usually fully recovers within few days, heart failure can still
      complicate the early phase. We report a case of stress-induced cardiomyopathy
      that had full recovery after 4 weeks of follow up. The main electrocardiographic,
      angiographic and imaging features are discussed. 

PMID- 24689017
TI  - Near-fatal cardiac arrest due to cardiac tamponade during percutaneous mitral
      valvuloplasty.
AB  - The incidence of hemopericardium following percutaneous mitral valvuloplasty is
      reported at 1-3%, being related to either trans-septal puncture, or left
      ventricular perforation with guide wires or balloons. We report a case of
      percutaneous mitral valvuloplasty for a middle-aged man with moderately severe
      rheumatic mitral stenosis. The procedure was performed through a right femoral
      vein approach, employing the multitrack technique, utilizing 2 balloons (20 and
      18 mm). Inadvertently, the procedure was complicated by cardiac tamponade.
      Despite immediate diagnosis and prompt pericardiocentesis, hemodynamic stability
      was not maintained. Echocardiography revealed a mass in the posterior pericardial
      sac. The patient was arrested in asystole, and rigorously resuscitated during
      transfer to the operating room. Exploration revealed a tear in the left
      ventricular apex that was adequately sutured. In a few days, the patient
      gradually regained adequate consciousness, and was ultimately discharged. Post
      procedural echocardiography revealed a mitral valve area of 1.9 cm(2), with no
      mitral regurgitation. 

PMID- 24689018
TI  - Managing atrial fibrillation in the global community: The European perspective.
AB  - Atrial fibrillation is a common, global problem, with great personal, economic
      and social burdens. As populations age it increases in prevalence and becomes
      another condition that requires careful chronic management to ensure its effects
      are minimised. Assessment of the risk of stroke using well established risk
      prediction models is being aided by modern computerised databases and the choice
      of drugs to prevent strokes is ever expanding to try and improve the major cause
      of morbidity in AF. In addition, newer drugs for controlling rhythm are available
      and guidelines are constantly changing to reflect this. As well as medications,
      modern techniques of electrophysiology are becoming more widely embraced
      worldwide to provide more targeted treatment for the underlying pathophysiology.
      In this review we consider these factors to concisely describe how AF can be
      successfully managed. 

PMID- 24689019
TI  - Right ventricular mechanics in hypertrophic cardiomyopathy using feature
      tracking.
AB  - OBJECTIVES: Right ventricular (RV) mechanics in hypertrophic cardiomyopathy (HCM)
      are poorly understood. We investigate global and regional deformation of the RV
      in HCM and its relationship to LV phenotype, using 2D strain vector velocity
      imaging (VVI). METHODS: 100 HCM patients (42% females, 41 +/- 19 years) and 30
      control patients were studied using VVI. Longitudinal peak systolic strain
      (epsilonsys), strain rate (SR), time to peak (epsilon) (TTP), displacement of RV
      free wall (RVFW) and septal wall were analyzed. Similar parameters were
      quantified in LV septal, lateral, anterior and inferior segments. Intra-V-delay
      was defined as SD of TTP. Inter-V-delay was estimated from TTP difference between
      the most delayed LV segment & RVFW. RESULTS: epsilonsys and SR of both RV & LV,
      showed loss of base to apex gradient and significant decline in HCM (p < 0.001).
      Deformation variables estimated from RVFW were strongly correlated with each
      other (r = 0.93, p < 0.0001). Both were directly related to LV epsilonsys, SRsys,
      SRe, ejection fraction (EF)%, RVFW displacement (P < 0.001) and inversely related
      to age, positive family history (p < 0.004, 0.005), RV wall thickness, maximum
      wall thickness (MWT), intra-V-delay, LA volume (P < 0.0001), LVOT gradient (p <
      0.02, 0.005) respectively. ROC curves were constructed to explore the cut-off
      point that discriminates RV dysfunction. Global and RVFW epsilonsys: - 19.5%
      shows 77, 70% sensitivity & 97% specificity, SRsys: - 1.3s(- 1) shows 82, 70%
      sensitivity & 30% specificity. Multivariate analyses revealed that RVFW
      displacement (beta = - 0.9, p < 0.0001) and global LV SRsys (beta = 5.9, p <
      0.0001) are independent predictors of global RV deformation. CONCLUSIONS:
      Impairment of RV deformation is evident in HCM using feature tracking. It is
      independently influenced by LV mechanics and correlated to the severity of LV
      phenotype. RVFW deformation analysis and global RV assessment are comparable.

PMID- 24689020
TI  - Successful ablation of two right atrial tachycardias on either side of the
      lateral tunnel patch in a patient with double inlet left ventricle and total
      cavopulmonary connection: Two sites and two mechanisms.

PMID- 24689021
TI  - Off-pump coronary artery bypass grafting (OPCABG): the beginning of the end?

PMID- 24689022
TI  - Clinical trials of bone marrow derived cells for ischemic heart failure. Time to
      move on? TIME, SWISS-AMI, CELLWAVE, POSEIDON and C-CURE.

PMID- 24689023
TI  - Harnessing the power of dividing cardiomyocytes.
AB  - Lower vertebrates, such as newt and zebrafish, retain a robust cardiac
      regenerative capacity following injury. Recently, our group demonstrated that
      neonatal mammalian hearts have a remarkable regenerative potential in the first
      few days after birth. Although adult mammals lack this regenerative potential, it
      is now clear that there is measurable cardiomyocyte turnover that occurs in the
      adult mammalian heart. In both neonatal and adult mammals, proliferation of pre
      existing cardiomyocytes appears to be the underlying mechanism of myocyte
      turnover. This review will highlight the advances and landmark studies that
      opened new frontiers in cardiac regeneration. 

PMID- 24689025
TI  - Hypertrophic cardiomyopathy: The need for randomized trials.
AB  - Hypertrophic cardiomyopathy (HCM) is a complex cardiac condition characterized by
      variable degrees of asymmetric left ventricular (LV) hypertrophy, generally
      associated with mutations in sarcomere protein genes. While generally perceived
      as rare, HCM is the most common genetic heart disease with over one million
      affected individuals in Europe alone and represents a prevalent cause of sudden
      cardiac death in the young. To date, HCM remains an orphan disease, as
      recommended treatment strategies are based on the empirical use of old drugs with
      little evidence supporting their clinical benefit in this context. In the six
      decades since the original description of the disease, less than fifty
      pharmacological studies have been performed in HCM patients, enrolling little
      over 2,000 HCM patients, mostly comprising small non-randomized cohorts. No
      specific agent has been convincingly shown to affect outcome, and critical issues
      such as prevention of myocardial energy depletion, microvascular ischemia,
      progressive myocardial fibrosis and the peculiar mechanisms of arrhythmogenesis
      in HCM still need to be addressed in a systematic fashion. However, there is
      increasing evidence that a variety of drugs may counter the effects of sarcomere
      protein mutations and the resulting pathophysiological abnormalities at the
      molecular, cellular and organ level. Following major advances in our
      understanding of HCM and increasing opportunities for networking among large
      international referral centres, the opportunity now exists to identify
      potentially effective treatments and implement adequately designed
      pharmacological trials, with the ultimate aim to impact the natural course of the
      disease, alleviate symptoms and improve quality of life in our patients. 

PMID- 24689026
TI  - The science and practice of cardiopulmonary bypass: From cross circulation to
      ECMO and SIRS.

PMID- 24689024
TI  - Regulation of intracellular Na(+) in health and disease: pathophysiological
      mechanisms and implications for treatment.
AB  - Transmembrane sodium (Na(+)) fluxes and intracellular sodium homeostasis are
      central players in the physiology of the cardiac myocyte, since they are crucial
      for both cell excitability and for the regulation of the intracellular calcium
      concentration. Furthermore, Na(+) fluxes across the membrane of mitochondria
      affect the concentration of protons and calcium in the matrix, regulating
      mitochondrial function. In this review we first analyze the main molecular
      determinants of sodium fluxes across the sarcolemma and the mitochondrial
      membrane and describe their role in the physiology of the healthy myocyte. In
      particular we focus on the interplay between intracellular Ca(2+) and Na(+). A
      large part of the review is dedicated to discuss the changes of Na(+) fluxes and
      intracellular Na(+) concentration([Na(+)]i) occurring in cardiac disease; we
      specifically focus on heart failure and hypertrophic cardiomyopathy, where
      increased intracellular [Na(+)]i is an established determinant of myocardial
      dysfunction. We review experimental evidence attributing the increase of [Na(+)]i
      to either decreased Na(+) efflux (e.g. via the Na(+)/K(+) pump) or increased
      Na(+) influx into the myocyte (e.g. via Na(+) channels). In particular, we focus
      on the role of the "late sodium current" (INaL), a sustained component of the
      fast Na(+) current of cardiac myocytes, which is abnormally enhanced in cardiac
      diseases and contributes to both electrical and contractile dysfunction. We
      analyze the pathophysiological role of INaL enhancement in heart failure and
      hypertrophic cardiomyopathy and the consequences of its pharmacological
      modulation, highlighting the clinical implications. The central role of Na(+)
      fluxes and intracellular Na(+) physiology and pathophysiology of cardiac myocytes
      has been highlighted by a large number of recent works. The possibility of
      modulating Na(+) inward fluxes and [Na(+)]i with specific INaL inhibitors, such
      as ranolazine, has made Na(+)a novel suitable target for cardiac therapy,
      potentially capable of addressing arrhythmogenesis and diastolic dysfunction in
      severe conditions such as heart failure and hypertrophic cardiomyopathy. 

PMID- 24689027
TI  - Syncope and recurrent ventricular tachycardia with a newly identified desmosomal
      gene mutation.
AB  - Ventricular arrhythmias in young people most commonly occur due to the presence
      of hypertrophic cardiomyopathy, long QT syndrome or Wolff-Parkinson-White
      syndrome. We present a case in which the patient had exercise induced syncopal
      spells and was found to have ventricular tachycardia (VT) during both exercise
      stress testing and an electrophysiology study. Further genetic studies showed a
      previously unseen desmosomal gene mutation confirming the presence of
      Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). 

PMID- 24689028
TI  - RAAS inhibition and mortality in hypertension.
AB  - The renin-angiotensin-aldosterone system (RAAS) regulates the body's hemodynamic
      equilibrium, circulating volume, and electrolyte balance, and is a key
      therapeutic target in hypertension, the world's leading cause of premature
      mortality. Hypertensive disorders are strongly linked with an overactive RAAS,
      and RAAS inhibitors, like angiotensin-converting enzyme (ACE) inhibitors and
      angiotensin receptor blockers (ARBs), are routinely used to treat high blood
      pressure (BP). BP reduction is one of the main goals of current European
      hypertension guidelines. Oral ACE inhibitors, the oldest category of RAAS
      inhibitor, were commercially released over 30 years ago in the early 1980s, over
      a decade before the first ARBs became available. The introduction of ACE
      inhibitors heralded major changes in the way hypertension and cardiovascular
      disease were treated. Although the decision of the medical community to replace
      older ACE inhibitors with more modern ARBs in the 1990s was debatable, it did
      nevertheless allow scientists to learn more about the angiotensin receptors
      involved in RAAS stimulation. This and much else of value have been discovered
      since RAAS inhibitors first became available, but some surprising gaps in our
      knowledge exist. Until recently, the effect of RAAS inhibition on mortality in
      hypertension was unknown. This question was recently addressed by a meta-analysis
      of randomized controlled trials in populations who received contemporary
      antihypertensive medication. The results of this meta-analysis have helped
      elucidate the long-term consequences of treatment with RAAS inhibitors on
      mortality in hypertension. This article will consider the differences between
      RAAS inhibitors in terms of pharmacological and clinical effects and analyze the
      impact of the main types of RAAS inhibitor, ACE inhibitors and ARBs, on mortality
      reduction in hypertensive patients with reference to this latest meta-analysis. 

PMID- 24689029
TI  - Editors' page.

PMID- 24689030
TI  - Three-dimensional structure of the human myosin thick filament: clinical
      implications.
AB  - High resolution information about the three-dimensional (3D) structure of myosin
      filaments has always been hard to obtain. Solving the 3D structure of myosin
      filaments is very important because mutations in human cardiac muscle myosin and
      its associated proteins (e.g. titin and myosin binding protein C) are known to be
      associated with a number of familial human cardiomyopathies (e.g. hypertrophic
      cardiomyopathy and dilated cardiomyopathy). In order to understand how normal
      heart muscle works and how it fails, as well as the effects of the known
      mutations on muscle contractility, it is essential to properly understand myosin
      filament 3D structure and properties in both healthy and diseased hearts. The aim
      of this review is firstly to provide a general overview of the 3D structure of
      myosin thick filaments, as studied so far in both vertebrates and invertebrate
      striated muscles. Knowledge of this 3D structure is the starting point from which
      myosin filaments isolated from human cardiomyopathic samples, with known
      mutations in either myosin or its associated proteins (titin or C-protein), can
      be studied in detail. This should, in turn, enable us to relate the structure of
      myosin thick filament to its function and to understanding the disease process. A
      long term objective of this research would be to assist the design of possible
      therapeutic solutions to genetic myosin-related human cardiomyopathies. 

PMID- 24689031
TI  - Cardiomyocyte proliferation vs progenitor cells in myocardial regeneration: The
      debate continues.
AB  - In recent years, several landmark studies have provided compelling evidence that
      cardiomyogenesis occurs in the adult mammalian heart. However, the rate of new
      cardiomyocyte formation is inadequate for complete restoration of the normal mass
      of myocardial tissue, should a significant myocardial injury occur, such as
      myocardial infarction. The cellular origin of postnatal cardiomyogenesis in
      mammals remains a controversial issue and two mechanisms seem to be
      participating, proliferation of pre-existing cardiomyocytes and myogenic
      differentiation of progenitor cells. We will discuss the relative importance of
      these two processes in different settings, such as normal ageing and post
      myocardial injury, as well as the strengths and limitations of the existing
      experimental methodologies used in the relevant studies. Further clarification of
      the mechanisms underlying cardiomyogenesis in mammals will open the way for their
      therapeutic exploitation in the clinical field, with the scope of myocardial
      regeneration. 

PMID- 24689033
TI  - Network-assisted prediction of potential drugs for addiction.
AB  - Drug addiction is a chronic and complex brain disease, adding much burden on the
      community. Though numerous efforts have been made to identify the effective
      treatment, it is necessary to find more novel therapeutics for this complex
      disease. As network pharmacology has become a promising approach for drug
      repurposing, we proposed to apply the approach to drug addiction, which might
      provide new clues for the development of effective addiction treatment drugs. We
      first extracted 44 addictive drugs from the NIDA and their targets from DrugBank.
      Then, we constructed two networks: an addictive drug-target network and an
      expanded addictive drug-target network by adding other drugs that have at least
      one common target with these addictive drugs. By performing network analyses, we
      found that those addictive drugs with similar actions tended to cluster together.
      Additionally, we predicted 94 nonaddictive drugs with potential pharmacological
      functions to the addictive drugs. By examining the PubMed data, 51 drugs
      significantly cooccurred with addictive keywords than expected. Thus, the network
      analyses provide a list of candidate drugs for further investigation of their
      potential in addiction treatment or risk. 

PMID- 24689032
TI  - Hydrogel scaffolds for tissue engineering: Progress and challenges.
AB  - Designing of biologically active scaffolds with optimal characteristics is one of
      the key factors for successful tissue engineering. Recently, hydrogels have
      received a considerable interest as leading candidates for engineered tissue
      scaffolds due to their unique compositional and structural similarities to the
      natural extracellular matrix, in addition to their desirable framework for
      cellular proliferation and survival. More recently, the ability to control the
      shape, porosity, surface morphology, and size of hydrogel scaffolds has created
      new opportunities to overcome various challenges in tissue engineering such as
      vascularization, tissue architecture and simultaneous seeding of multiple cells.
      This review provides an overview of the different types of hydrogels, the
      approaches that can be used to fabricate hydrogel matrices with specific features
      and the recent applications of hydrogels in tissue engineering. Special attention
      was given to the various design considerations for an efficient hydrogel scaffold
      in tissue engineering. Also, the challenges associated with the use of hydrogel
      scaffolds were described. 

PMID- 24689034
TI  - Identification of a chicken anemia virus variant-related gyrovirus in stray cats
      in china, 2012.
AB  - The chicken anemia virus (CAV), is a known member of the genus Gyrovirus and was
      first isolated from chickens in Japan in 1979. Some reports have also
      demonstrated that CAV can be identified in human stool specimens. In this study,
      a variant of CAV was detected using PCR with CAV-based primers in fecal samples
      of stray cats. The genome of CAV variant was sequenced and the results suggest
      that it could be a recombinant viral strain from parental CAV strains JQ690762
      and AF311900. Recombination is an important evolutionary mechanism that
      contributes to genetic diversification. These findings indicate that CAV variant
      might have originated from CAV-infected chickens. The epidemiology and
      pathogenesis of this novel virus remains to be elucidated. This study underscores
      the importance of CAV surveillance and it presents the first evidence suggesting
      the possibility of CAV homologous recombination in cat. 

PMID- 24689035
TI  - ROS, Notch, and Wnt signaling pathways: crosstalk between three major regulators
      of cardiovascular biology.
AB  - Reactive oxygen species (ROS), traditionally viewed as toxic by-products that
      cause damage to biomolecules, now are clearly recognized as key modulators in a
      variety of biological processes and pathological states. The development and
      regulation of the cardiovascular system require orchestrated activities; Notch
      and Wnt/beta -catenin signaling pathways are implicated in many aspects of them,
      including cardiomyocytes and smooth muscle cells survival, angiogenesis,
      progenitor cells recruitment and differentiation, arteriovenous specification,
      vascular cell migration, and cardiac remodelling. Several novel findings
      regarding the role of ROS in Notch and Wnt/beta-catenin modulation prompted us to
      review their emerging function in the cardiovascular system during embryogenesis
      and postnatally.

PMID- 24689037
TI  - Feasibility of piezoelectric endoscopic transsphenoidal craniotomy: a cadaveric
      study.
AB  - OBJECTIVE: Endoscopic transsphenoidal approach has become the gold standard for
      surgical treatment of treating pituitary adenomas or other lesions in that area.
      Opening of bony skull base has been performed with burrs, chisels, and hammers or
      standard instruments like punches and circular top knives. The creation of
      primary bone flaps-as in external craniotomies-is difficult.The piezoelectric
      osteotomes used in the present study allows creating a bone flap for endoscopic
      transnasal approaches in certain areas. The aim of this study was to prove the
      feasibility of piezoelectric endoscopic transnasal craniotomies. Study Design.
      Cadaveric study. METHODS: On cadaveric specimens (N = 5), a piezoelectric system
      with specially designed hardware for endonasal application was applied and
      endoscopic transsphenoidal craniotomies at the sellar floor, tuberculum sellae,
      and planum sphenoidale were performed up to a size of 3-5 cm(2). RESULTS: Bone
      flaps could be created without fracturing with the piezoosteotome and could be
      reimplanted. Endoscopic handling was unproblematic and time required was not
      exceeding standard procedures. CONCLUSION: In a cadaveric model, the
      piezoelectric endoscopic transsphenoidal craniotomy (PETC) is technically
      feasible. This technique allows the surgeon to create a bone flap in endoscopic
      transnasal approaches similar to existing standard transcranial craniotomies.
      Future trials will focus on skull base reconstruction using this bone flap.

PMID- 24689036
TI  - A novel role for raloxifene nanomicelles in management of castrate resistant
      prostate cancer.
AB  - Of patients with castrate resistant prostate cancer (CRPC), less than 25-33%
      survive more than five years. Recent studies have implicated estrogen, acting
      either alone or synergistically with androgens in the development of castrate
      resistant prostate cancer. Several in vitro and in vivo studies, as well as a
      limited number of clinical trials, have highlighted the potential of selective
      estrogen receptor modulators, such as raloxifene (Ral) for the treatment of
      castrate resistant prostate cancer. However, the poor oral bioavailability and
      metabolism of selective estrogen receptor modulators limit their efficiency in
      clinical application. To overcome these limitations, we have used styrene co
      maleic acid (SMA) micelle to encapsulate raloxifene. Compared to free drug, SMA
      Ral micelles had 132 and 140% higher cytotoxicity against PC3 and DU 145 prostate
      cell lines, respectively. SMA-Ral effectively inhibits cell cycle progression,
      increases apoptosis, and alters the integrity of tumor spheroid models. In
      addition, the micellar system induced changes in expression and localization of
      estrogen receptors, epidermal growth factor receptor (EGFR), and downstream
      effectors associated with cell proliferation and survival. Finally, SMA-Ral
      treatment decreased migration and invasion of castrate resistant prostate cancer
      cell lines. In conclusion, SMA-Ral micelles can potentially benefit new
      strategies for clinical management of castrate resistant prostate cancer. 

PMID- 24689038
TI  - Decreased thioredoxin-1 and increased HSP90 expression in skeletal muscle in
      subjects with type 2 diabetes or impaired glucose tolerance.
AB  - In diabetes, the endogenous defence systems are overwhelmed, causing various
      types of stress in tissues. In this study, newly diagnosed or diet-treated type 2
      diabetics (T2D) (n = 10) were compared with subjects with impaired glucose
      tolerance (IGT) (n = 8). In both groups, at resting conditions, blood samples
      were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus
      lateralis) were taken for the measurements of cellular defence markers:
      thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX
      1 was 36.1% lower (P = 0.031) and HSP90 was 380% higher (P < 0.001) in the T2D
      than in the IGT subjects, with no significant changes in HSP72. However, after
      the adjustment of both analyses with HOMA-IR only HSP90 difference remained
      significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower
      while that of HSP90 was higher in T2D than in IGT subjects. This may impair
      antioxidant defence and lead to disruptions of protein homoeostasis and redox
      regulation of cellular defences. Because HSP90 may be involved in sustaining
      functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90
      levels can be a consequence of type 2 diabetes, our results are potentially
      important for the diabetes research. 

PMID- 24689039
TI  - Enhancement of biodiesel production from marine alga, Scenedesmus sp. through in
      situ transesterification process associated with acidic catalyst.
AB  - The aim of this study was to increase the yield of biodiesel produced by
      Scenedesmus sp. through in situ transesterification by optimizing various process
      parameters. Based on the orthogonal matrix analysis for the acidic catalyst, the
      effects of the factors decreased in the order of reaction temperature (47.5%) >
      solvent quantity (26.7%) > reaction time (17.5%) > catalyst amount (8.3%). Based
      on a Taguchi analysis, the effects of the factors decreased in the order of
      solvent ratio (34.36%) > catalyst (28.62%) > time (19.72%) > temperature
      (17.32%). The overall biodiesel production appeared to be better using NaOH as an
      alkaline catalyst rather than using H2SO4 in an acidic process, at 55.07 +/-
      2.18% (based on lipid weight) versus 48.41 +/- 0.21%. However, in considering the
      purified biodiesel, it was found that the acidic catalyst was approximately 2.5
      times more efficient than the alkaline catalyst under the following optimal
      conditions: temperature of 70  degrees C (level 2), reaction time of 10 hrs
      (level 2), catalyst amount of 5% (level 3), and biomass to solvent ratio of 1 :
      15 (level 2), respectively. These results clearly demonstrated that the acidic
      solvent, which combined oil extraction with in situ transesterification, was an
      effective catalyst for the production of high-quantity, high-quality biodiesel
      from a Scenedesmus sp.

PMID- 24689040
TI  - Contribution of psychological factors in dropping out from chronic obstructive
      pulmonary disease rehabilitation programs.
AB  - Significant positive effects, particularly on psychological state in patients who
      completed the follow-up pulmonary rehabilitation programs, are indicated by a
      large number of studies. Yet, a remarkable proportion of selected patients drop
      out from these programs. In this study, we investigated existing differences on
      psychological variables among COPD patients who complete and those who drop out
      from pulmonary rehabilitation programs. The study included 144 patients, 43
      (29.9%) of whom did not complete the program. SCL-90 was used for the assessment
      of psychological symptoms. On the SCL-90-R scale 55.6% of patients had abnormal
      findings. Patients who discontinued the program had higher rates of depression
      and somatization compared to those who completed it. Regarding the
      psychopathology scales of SCL-90R, we found that patients who discontinued the
      program showed higher levels of psychopathology on the scales of somatization,
      depression, paranoid ideation, and psychotism compared to those who completed the
      program. The final regression model showed that patients with low educational
      status and psychotism were more likely to leave the program. In conclusion,
      psychopathology contributes to patients dropping out from a COPD rehabilitation
      program; thus, psychological assessment prior to inclusion in rehabilitation
      programs may reduce dropouts. 

PMID- 24689041
TI  - Emulsion electrospinning as an approach to fabricate PLGA/chitosan nanofibers for
      biomedical applications.
AB  - Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan
      have been produced through an emulsion electrospinning process. The spinning
      solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted
      from the electrospun nanofibers, resulting in a final scaffold consisting of a
      blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat
      was adjusted from 0 to 33%. Analyses by scanning and transmission electron
      microscopy show uniform nanofibers with homogenous distribution of PLGA and
      chitosan in their cross section. Infrared spectroscopy verifies that electrospun
      mats contain both PLGA and chitosan. Moreover, contact angle measurements show
      that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun
      mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan
      in dry and wet conditions, respectively, illustrate that the polyblend mats of
      PLGA/chitosan are strong enough for many biomedical applications. Cell culture
      studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and
      proliferation compared to PLGA membranes. It can be assumed that the nanofibrous
      composite scaffold of PLGA/chitosan could be potentially used for skin tissue
      reconstruction.

PMID- 24689042
TI  - Maternal OGTT glucose levels at 26-30 gestational weeks with offspring growth and
      development in early infancy.
AB  - AIMS: We aim to evaluate the association of maternal gestational oral glucose
      tolerance test (OGTT) glucose concentrations with anthropometry in the offspring
      from birth to 12 months in Tianjin, China. METHODS: A total of 27,157 pregnant
      women underwent OGTT during 26-30 weeks gestation, and their children had body
      weight/length measured from birth to 12 months old. RESULTS: Maternal OGTT
      glucose concentrations at 26-30 gestational weeks were positively associated with
      Z-scores for birth length-for-gestational age and birth weight-for-length.
      Compared with infants born to mothers with normal glucose tolerance, infants born
      to mothers with gestational diabetes mellitus (impaired glucose tolerance/new
      diabetes) had higher mean values of Z-scores for birth length-for-gestational age
      (0.07/0.23; normal group -0.08) and birth weight-for-length (0.27/0.57; normal
      group -0.001), smaller changes in mean values of Z-scores for length-for-age
      (0.75/0.62; normal group 0.94) and weight-for-length (0.18/-0.17; normal group
      0.37) from birth to month 3, and bigger changes in mean values in Z-scores for
      weight-for-length (0.07/0.12; normal group 0.02) from month 9 to 12. CONCLUSIONS:
      Abnormal maternal glucose tolerance during pregnancy was associated with higher
      birth weight and birth length, less weight and length gain in the first 3 months
      of life, and more weight gain in the months 9-12 of life.

PMID- 24689043
TI  - Effect of hyaluronan on developmental competence and quality of oocytes and
      obtained blastocysts from in vitro maturation of bovine oocytes.
AB  - The objective of the present study was to evaluate the effect of hyaluronan (HA)
      during IVM on meiotic maturation, embryonic development, and the quality of
      oocytes, granulosa cells (GC), and obtained blastocysts. COCs were matured in
      vitro in control medium and medium with additional 0.035% or 0.07% of exogenous
      HA. The meiotic maturity did not differ between the analysed groups. The best
      rate and the highest quality of obtained blastocysts were observed when 0.07% HA
      was used. A highly significant difference (P < 0.001) was noted in the mean
      number of apoptotic nuclei per blastocyst and in the DCI between the 0.07% HA and
      the control blastocysts (P < 0.01). Our results suggest that addition of 0.035%
      HA and 0.07% HA to oocyte maturation media does not affect oocyte nuclear
      maturation and DNA fragmentation. However, the addition of 0.07% HA during IVM
      decreases the level of blastocysts DNA fragmentation. Finally, our results
      suggest that it may be risky to increase the HA concentration during IVM above
      0.07% as we found significantly higher Bax mRNA expression levels in GC cultured
      with 0.07% HA. The final concentration of HA being supplemented to oocyte
      maturation media is critical for the success of the IVP procedure. 

PMID- 24689044
TI  - Development of a reverse transcription loop-mediated isothermal amplification
      method for the rapid detection of subtype H7N9 avian influenza virus.
AB  - A novel influenza A (H7N9) virus has emerged in China. To rapidly detect this
      virus from clinical samples, we developed a reverse transcription loop-mediated
      isothermal amplification (RT-LAMP) method for the detection of the H7N9 virus.
      The minimum detection limit of the RT-LAMP assay was 0.01 PFU H7N9 virus, making
      this method 100-fold more sensitive to the detection of the H7N9 virus than
      conventional RT-PCR. The H7N9 virus RT-LAMP assays can efficiently detect
      different sources of H7N9 influenza virus RNA (from chickens, pigeons, the
      environment, and humans). No cross-reactive amplification with the RNA of other
      subtype influenza viruses or of other avian respiratory viruses was observed. The
      assays can effectively detect H7N9 influenza virus RNA in drinking water, soil,
      cloacal swab, and tracheal swab samples that were collected from live poultry
      markets, as well as human H7N9 virus, in less than 30 min. These results suggest
      that the H7N9 virus RT-LAMP assays were efficient, practical, and rapid
      diagnostic methods for the epidemiological surveillance and diagnosis of
      influenza A (H7N9) virus from different resource samples.

PMID- 24689045
TI  - Flow cytometry assessment of in vitro generated CD138+ human plasma cells.
AB  - The in vitro CD40-CD154 interaction promotes human B lymphocytes differentiation
      into plasma cells. Currently, CD138 is the hallmark marker enabling the detection
      of human plasma cells, both in vitro and in vivo; its presence can be monitored
      by flow cytometry using a specific antibody. We have developed a culture system
      allowing for the differentiation of memory B lymphocytes. In order to detect the
      newly formed plasma cells, we have compared their staining using five anti-CD138
      monoclonal antibodies (mAbs). As a reference, we also tested human cell lines,
      peripheral blood mononuclear cells, and bone marrow samples. The five anti-CD138
      mAbs stained RPMI-8226 cells (>98%) with variable stain index (SI). The highest
      SI was obtained with B-A38 mAb while the lowest SI was obtained with DL-101 and
      1D4 mAbs. However, the anti-CD138 mAbs were not showing equivalent CD138(+) cells
      frequencies within the generated plasma cells. B-A38, B-B4, and MI-15 were
      similar (15-25%) while DL-101 mAb stained a higher proportion of CD138-positive
      cells (38-42%). DL-101 and B-A38 mAbs stained similar populations in bone marrow
      samples but differed in their capacity to bind to CD138(high) and CD138(lo) cell
      lines. In conclusion, such cellular fluctuations suggest heterogeneity in human
      plasma cell populations and/or in CD138 molecules. 

PMID- 24689046
TI  - Effect of terbuthylazine-2-hydroxy at environmental concentrations on early life
      stages of common carp (Cyprinus carpio L.).
AB  - The aim of the study was to investigate effects of the triazine's herbicide
      terbuthylazine-2-hydroxy on early life stage of common carp (Cyprinus carpio L.)
      through antioxidant indices, mortality, growth, development, and histopathology.
      Based on accumulated mortality in the experimental groups, lethal concentrations
      of terbuthylazine-2-hydroxy were estimated at 35-day LC50 = 10.9 mg/L
      terbuthylazine-2-hydroxy. By day 15, fish were exposed to 3.5 mg/L and by day 26,
      fish were exposed to 0.0029 mg/L; real environmental concentration in Czech
      rivers, 0.07 mg/L, 1.4 mg/L, and 3.5 mg/L terbuthylazine-2-hydroxy, showed
      significantly lower mass and total length compared with controls. Based on
      inhibition of growth in the experimental groups, lowest observed effect
      concentration (LOEC) = 0.002 mg/L terbuthylazine-2-hydroxy and no observed effect
      concentration (NOEC) = 0.0001 mg/L terbuthylazine-2-hydroxy. No significant
      negative effects on hatching or embryo viability were demonstrated at the
      concentrations tested, but significant differences in early ontogeny among groups
      were noted. Fish from the two highest tested concentrations showed a dose-related
      delay in development compared with the controls. Total superoxide dismutase (SOD)
      activity was significant lower in all groups testedly for terbuthylazine-2
      hydroxy compared with the control group. At concentrations of 1.4 and 3.5 mg/L
      damage to caudal kidney tubules when compared to control fish was found.

PMID- 24689047
TI  - Comparison between conventional and real-time PCR assays for diagnosis of
      visceral leishmaniasis.
AB  - The diagnosis of visceral leishmaniasis (VL) is a challenging issue and several
      studies worldwide have evaluated the different tools to reach a diagnostic
      solution. The polymerase chain reaction (PCR) has proven to be effective in
      detecting the genome of Leishmania species in different biological samples. In
      this study, we compared the conventional PCR and real-time PCR using the Sybr
      Green system and their application in molecular diagnosis of visceral
      leishmaniasis in peripheral blood as a biological sample. The genus-specific
      conserved region of kinetoplast DNA (kDNA) was the target of amplification. We
      studied 30 samples from patients with suspect of visceral leishmaniasis who were
      treated by the Medical Clinic of Santa Casa de Belo Horizonte Hospital, Brazil.
      Among the samples studied, 19 had a confirmed diagnosis for VL by serology and/or
      by clinical findings. Among these 19 samples, 63% (n = 12) presented positive
      results for serology and 79% (n = 15) positive results in both PCR methodologies.
      This fact suggests that the PCR technique can assist in the diagnosis of visceral
      leishmaniasis in patients who do not have detectable antibodies by serology but
      can present the genome of the parasite circulating in whole blood. Also, it was
      possible to observe that there was conformity between the results of the
      techniques of cPCR and qPCR using the Sybr Green system in 100% of samples
      analyzed. These data suggest that both PCR techniques were equally effective for
      detection of the genome of the parasite in the patient's blood. 

PMID- 24689048
TI  - Tumour markers and kidney function: a systematic review.
AB  - Tumour markers represent useful tools in diagnosis and clinical management of
      patients with cancer, because they are easy to use, minimally invasive, and
      easily measured in either blood or urine. Unfortunately, such an ideal marker, as
      yet, does not exist. Different pathological states may increase the level of a
      tumour marker in the absence of any neoplasia. Alternatively, low levels of
      tumour markers could be also found in the presence of neoplasias. We aimed at
      reviewing studies currently available in the literature examining the association
      between tumour markers and different renal impairment conditions. Each tumour
      marker was found to be differently influenced by these criteria; additionally we
      revealed in many cases a lack of available published data. 

PMID- 24689049
TI  - Role of ROBO4 signalling in developmental and pathological angiogenesis.
AB  - Transmembrane roundabout receptor family members (ROBO1-ROBO4) principally
      orchestrate the neuronal guidance mechanism of the nervous system. Secreted
      glycoprotein SLITs are the most appreciated ligands for ROBOs. Recently
      identified ROBO4 is the key mediator of SLIT-ROBO mediated developmental and
      pathological angiogenesis. Although SLIT2 has been shown to interact with ROBO4
      as ligand, it remains an open question whether this protein is the physiologic
      partner of ROBO4. The purpose of this review is to summarise how reliable SLIT2
      as ligand for ROBO4 is, if not what the other possible mechanisms demonstrated
      till date for ROBO4 mediated developmental and pathological angiogenesis are. We
      conclude that ROBO4 is expressed specially in vascular endothelial cells and
      maintains the vascular integrity via either SLIT2 dependent or SLIT2 independent
      manner. On the contrary, it promotes the pathological angiogenesis by involving
      different signalling arm(s)/unknown ligand(s). This review explores the
      interactions SLIT2/ROBO1, SLIT2/ROBO1-ROBO4, ROBO1/ROBO4, and ROBO4/UNC5B which
      can be promising and potential therapeutic targets for developmental angiogenesis
      defects and pathological angiogenesis. Finally we have reviewed the ROBO4
      signalling pathways and made an effort to elaborate the insight of this
      signalling as therapeutic target of pathological angiogenesis. 

PMID- 24689050
TI  - Uptake of etoposide in CT-26 cells of colorectal cancer using folate targeted
      dextran stearate polymeric micelles.
AB  - Targeted drug delivery using folate receptors is one of the most interesting
      chemotherapeutic research areas over the past few years. A novel folate targeted
      copolymer was synthesized using dextran stearate coupled to folic acid. FT-IR and
      NMR spectroscopy were used to confirm successful conjugation. Micelles prepared
      using this copolymer were characterized for their particle size, zeta potential,
      critical micelle concentration (CMC), drug loading capacity, and release
      efficiency. Cytotoxicity and cellular uptake of the micelles were estimated using
      CT-26 colorectal carcinoma cell line. FT-IR and NMR spectroscopy confirmed
      production of folate grafted dextran stearate copolymer. Low CMC value indicates
      that the copolymers are suitable for preparation of stable micelles useful in
      parenteral dosage forms. Particle size and zeta potential of the targeted
      nanoparticles were 105.5 +/- 2.0 nm and -21.2 mV, respectively. IC50 of etoposide
      loaded in folate grafted dextran stearate enhanced about 20-fold compared to the
      pure drug (0.49 +/- 0.11 MUg/mL versus 9.41 +/- 0.52 MUg/mL). It seems that
      etoposide loaded in micelles of folate grafted dextran stearate copolymer is
      promising in reducing drug resistance of colorectal cancer by boosting etoposide
      cellular uptake.

PMID- 24689051
TI  - Mycobacterium avium Subsp. avium infection in four veal calves: differentiation
      from intestinal tuberculosis.
AB  - Mycobacterium avium subsp. avium (Maa) is an intracellular pathogen belonging to
      the Mycobacterium avium-intracellulare complex (MAC). Reservoirs of MAC are the
      natural environment, wildlife and domestic animals. In adult bovine, MAC
      infections are typically caused by Mycobacterium avium subsp. paratuberculosis
      (Map). Maa infections in bovine are rarely reported but may cause clinical
      disease and pathological lesions similar to those observed in paratuberculosis or
      those induced by members of the Mycobacterium tuberculosis complex (MTBC).
      Therefore, differentiation of MAC from MTBC infection should be attempted,
      especially if unusual mycobacterial lesions are encountered. Four veal calves
      from a fattening farm dying with clinical signs of otitis media, fever, and
      weight loss were submitted for necropsy. Samples from affected organs were taken
      for histologic investigation, bacteriologic culture, and bacterial specification
      using PCR. Macroscopic thickening of the intestinal mucosa was induced by
      granulomatous enteritis and colitis. Intracytoplasmic acid-fast bacteria were
      detected by Ziehl-Neelsen stains and PCR revealed positive results for
      Mycobacterium avium subsp. avium. Clinical and pathological changes of Maa
      infection in veal calves had features of Mycobacterium avium subsp.
      paratuberculosis and the MTBC. Therefore, Mycobacterium tuberculosis complex
      infection should be considered in cases of granulomatous enteritis in calves. 

PMID- 24689053
TI  - Ginseng is useful to enhance cardiac contractility in animals.
AB  - Ginseng has been shown to be effective on cardiac dysfunction. Recent evidence
      has highlighted the mediation of peroxisome proliferator-activated receptors
      (PPARs) in cardiac function. Thus, we are interested to investigate the role of
      PPARdelta in ginseng-induced modification of cardiac contractility. The isolated
      hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats
      were applied to measure the actions of ginseng ex vivo and in vivo. In normal
      rats, ginseng enhanced cardiac contractility and hemodynamic dP/dt(max)
      significantly. Both actions were diminished by GSK0660 at a dose enough to block
      PPARdelta. However, ginseng failed to modify heart rate at the same dose,
      although it did produce a mild increase in blood pressure. Data of intracellular
      calcium level and Western blotting analysis showed that both the PPARdelta
      expression and troponin I phosphorylation were raised by ginseng in neonatal rat
      cardiomyocyte. Thus, we suggest that ginseng could enhance cardiac contractility
      through increased PPARdelta expression in cardiac cells.

PMID- 24689052
TI  - Perspectives on molecular biomarkers of oxidative stress and antioxidant
      strategies in traumatic brain injury.
AB  - Traumatic brain injury (TBI) is frequently associated with abnormal blood-brain
      barrier function, resulting in the release of factors that can be used as
      molecular biomarkers of TBI, among them GFAP, UCH-L1, S100B, and NSE. Although
      many experimental studies have been conducted, clinical consolidation of these
      biomarkers is still needed to increase the predictive power and reduce the poor
      outcome of TBI. Interestingly, several of these TBI biomarkers are oxidatively
      modified to carbonyl groups, indicating that markers of oxidative stress could be
      of predictive value for the selection of therapeutic strategies. Some drugs such
      as corticosteroids and progesterone have already been investigated in TBI
      neuroprotection but failed to demonstrate clinical applicability in advanced
      phases of the studies. Dietary antioxidants, such as curcumin, resveratrol, and
      sulforaphane, have been shown to attenuate TBI-induced damage in preclinical
      studies. These dietary antioxidants can increase antioxidant defenses via
      transcriptional activation of NRF2 and are also known as carbonyl scavengers, two
      potential mechanisms for neuroprotection. This paper reviews the relevance of
      redox biology in TBI, highlighting perspectives for future studies. 

PMID- 24689054
TI  - Aberrant glycosylation as biomarker for cancer: focus on CD43.
AB  - Glycosylation is a posttranslational modification of proteins playing a major
      role in cell signalling, immune recognition, and cell-cell interaction because of
      their glycan branches conferring structure variability and binding specificity to
      lectin ligands. Aberrant expression of glycan structures as well as occurrence of
      truncated structures, precursors, or novel structures of glycan may affect ligand
      receptor interactions and thus interfere with regulation of cell adhesion,
      migration, and proliferation. Indeed, aberrant glycosylation represents a
      hallmark of cancer, reflecting cancer-specific changes in glycan biosynthesis
      pathways such as the altered expression of glycosyltransferases and glycosidases.
      Most studies have been carried out to identify changes in serum glycan
      structures. In most cancers, fucosylation and sialylation are significantly
      modified. Thus, aberrations in glycan structures can be used as targets to
      improve existing serum cancer biomarkers. The ability to distinguish differences
      in the glycosylation of proteins between cancer and control patients emphasizes
      glycobiology as a promising field for potential biomarker identification. In this
      review, we discuss the aberrant protein glycosylation associated with human
      cancer and the identification of protein glycoforms as cancer biomarkers. In
      particular, we will focus on the aberrant CD43 glycosylation as cancer biomarker
      and the potential to exploit the UN1 monoclonal antibody (UN1 mAb) to identify
      aberrant CD43 glycoforms. 

PMID- 24689055
TI  - The low chamber pancreatic cancer cells had stem-like characteristics in modified
      transwell system: is it a novel method to identify and enrich cancer stem-like
      cells?
AB  - Cancer stem cells (CSCs) or cancer-initiating cells (CICs) play an important role
      in tumor initiation, progression, metastasis, chemoresistance, and recurrence. It
      is important to construct an effective method to identify and isolate CSCs for
      biotherapy of cancer. During the past years, many researchers had paid more
      attention to it; however, this method was still on seeking. Therefore, compared
      to the former methods that were used to isolate the cancer stem cell, in the
      present study, we tried to use modified transwell system to isolate and enrich
      CSCs from human pancreatic cancer cell lines (Panc-1). Our results clearly showed
      that the lower chamber cells in modified transwell system were easily forming
      spheres; furthermore, these spheres expressed high levels of stem cell markers
      (CD133/CD44/CD24/Oct-4/ESA) and exhibited chemoresistance, underwent epithelial
      to-mesenchymal transition (EMT), and possessed the properties of self-renewal in
      vitro and tumorigenicity in vivo. Therefore, we speculated that modified
      transwell assay system, as a rapid and effective method, can be used to isolate
      and enrich CSCs. 

PMID- 24689056
TI  - Clinical outcomes after treatment of periodontal intrabony defects with
      nanocrystalline hydroxyapatite (Ostim) or enamel matrix derivatives (Emdogain): a
      randomized controlled clinical trial.
AB  - INTRODUCTION: Periodontitis is an inflammatory process in response to dental
      biofilm and leads to periodontal tissue destruction. The aim of this study was
      the comparison of outcomes using either an enamel matrix derivative (EMD) or a
      nanocrystalline hydroxyapatite (NHA) in regenerative periodontal therapy after 6
      and 12 months. METHODS: Using a parallel group, prospective randomized study
      design, we enrolled 19 patients in each group. The primary outcome was bone fill
      after 12 months. Attachment gain, probing pocket depth (PPD) reduction, and
      recession were secondary variables. Additionally, early wound healing and adverse
      events were assessed. Data analysis included test of noninferiority of NHA group
      (test) compared to EMD group (reference) in bone fill. Differences in means of
      secondary variables were compared by paired t-test, frequency data by exact
      chi(2) test. RESULTS: Both groups showed significant bone fill, reduction of PPD,
      increase in recession, and gain of attachment after 6 and 12 months. No
      significant differences between groups were found at any time point. Adverse
      events were comparable between both groups with a tendency of more complaints in
      the NHA group. CONCLUSION: The clinical outcomes were similar in both groups. EMD
      could have some advantage compared to NHA regarding patients comfort and adverse
      events. The trial is registered with ClinicalTrials.gov NCT00757159.

PMID- 24689057
TI  - Genetic control of immune response and susceptibility to infectious diseases.

PMID- 24689059
TI  - Chemodynamics of methyl parathion and ethyl parathion: adsorption models for
      sustainable agriculture.
AB  - The toxicity of organophosphate insecticides for nontarget organism has been the
      subject of extensive research for sustainable agriculture. Pakistan has banned
      the use of methyl/ethyl parathions, but they are still illegally used. The
      present study is an attempt to estimate the residual concentration and to suggest
      remedial solution of adsorption by different types of soils collected and
      characterized for physicochemical parameters. Sorption of pesticides in soil or
      other porous media is an important process regulating pesticide transport and
      degradation. The percentage removal of methyl parathion and ethyl parathion was
      determined through UV-Visible spectrophotometer at 276 nm and 277 nm,
      respectively. The results indicate that agricultural soil as compared to barren
      soil is more efficient adsorbent for both insecticides, at optimum batch
      condition of pH 7. The equilibrium between adsorbate and adsorbent was attained
      in 12 hours. Methyl parathion is removed more efficiently (by seven orders of
      magnitude) than ethyl parathion. It may be attributed to more available binding
      sites and less steric hindrance of methyl parathion. Adsorption kinetics
      indicates that a good correlation exists between distribution coefficient (Kd)
      and soil organic carbon. A general increase in Kd is noted with increase in
      induced concentration due to the formation of bound or aged residue.

PMID- 24689058
TI  - Advance of molecular imaging technology and targeted imaging agent in imaging and
      therapy.
AB  - Molecular imaging is an emerging field that integrates advanced imaging
      technology with cellular and molecular biology. It can realize noninvasive and
      real time visualization, measurement of physiological or pathological process in
      the living organism at the cellular and molecular level, providing an effective
      method of information acquiring for diagnosis, therapy, and drug development and
      evaluating treatment of efficacy. Molecular imaging requires high resolution and
      high sensitive instruments and specific imaging agents that link the imaging
      signal with molecular event. Recently, the application of new emerging chemical
      technology and nanotechnology has stimulated the development of imaging agents.
      Nanoparticles modified with small molecule, peptide, antibody, and aptamer have
      been extensively applied for preclinical studies. Therapeutic drug or gene is
      incorporated into nanoparticles to construct multifunctional imaging agents which
      allow for theranostic applications. In this review, we will discuss the
      characteristics of molecular imaging, the novel imaging agent including targeted
      imaging agent and multifunctional imaging agent, as well as cite some examples of
      their application in molecular imaging and therapy. 

PMID- 24689060
TI  - High expression of leucine zipper-EF-hand containing transmembrane protein 1
      predicts poor prognosis in head and neck squamous cell carcinoma.
AB  - Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a
      mitochondrial inner membrane protein and plays an important role in mitochondrial
      ATP production and biogenesis. High expression levels of LETM1 have been
      correlated with numerous human malignancies. This study explored the
      clinicopathological significance of LETM1 expression as a prognostic determinant
      in head and neck squamous cell carcinoma (HNSCC). HNSCC samples from 176 patients
      were selected for immunohistochemical staining of LETM1 protein. Correlations
      between LETM1 overexpression and clinicopathological features of HNSCC were
      evaluated by Chi-squared tests and Fisher's exact tests, and relationships
      between prognostic factors and patient survival were analyzed using Cox
      proportional hazards models. Our results demonstrated that the strongly positive
      rate of LETM1 protein was 65.3% in HNSCC, which was significantly higher than in
      either adjacent nontumor tissue (25.0%) or normal squamous epithelia (6.7%).
      LETM1 overexpression correlated with poor differentiation, presence of lymph node
      metastasis, advanced stage, absence of chemoradiotherapy, and 5-year disease-free
      survival and overall survival rates in HNSCC. Further analysis showed that high
      LETM1 expression, advanced stage, and nonchemoradiotherapy were significant
      independent risk factors for mortality in HNSCC. In conclusion, LETM1 plays an
      important role in the progression of HNSCC and is an independent poor prognostic
      factor for HNSCC. 

PMID- 24689061
TI  - The 14 bp Del/Ins HLA-G polymorphism is related with high blood pressure in acute
      coronary syndrome and type 2 diabetes mellitus.
AB  - Immunologic and inflammatory processes are involved in the pathogenesis of acute
      coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte
      antigen-G (HLA-G) is a negative regulator of the immune response. This study
      evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and
      seventy individuals from Western Mexico were recruited and categorized into three
      groups: ACS (86), DM2 without coronary complications (70), and healthy subjects
      (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR
      and Native-PAGE. The most common risk factors were hypertension and overweight in
      ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G
      polymorphism showed no significant differences between groups (P >= 0.23).
      Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP)
      in the DM2 group (OR(c) = 1.65, P = 0.02). The genetic recessive model showed
      similar findings (OR(c) = 3.03, P = 0.04). No association was found in ACS, with
      a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar
      to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not
      a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have
      contributed to the development of HBP in the studied groups.

PMID- 24689062
TI  - Hypoglycemia is independently associated with multidimensional impairment in
      elderly diabetic patients.
AB  - AIM: To identify the characteristics associated with multidimensional impairment,
      evaluated through the Multidimensional Prognostic Index (MPI), a validated
      predictive tool for mortality derived from a standardized Comprehensive Geriatric
      Assessment (CGA), in a cohort of elderly diabetic patients treated with oral
      hypoglycemic drugs. METHODS AND RESULTS: The study population consisted of 1342
      diabetic patients consecutively enrolled in 57 diabetes centers distributed
      throughout Italy, within the Metabolic Study. Inclusion criteria were diagnosis
      of type 2 diabetes mellitus (DM), 65 years old or over, and treatment with oral
      antidiabetic medications. Data concerning DM duration, medications for DM taken
      during the 3-month period before inclusion in the study, number of hypoglycemic
      events, and complications of DM were collected. Multidimensional impairment was
      assessed using the MPI evaluating functional, cognitive, and nutritional status;
      risk of pressure sores; comorbidity; number of drugs taken; and cohabitation
      status. The mean age of participants was 73.3 +/- 5.5 years, and the mean MPI
      score was 0.22 +/- 0.13. Multivariate analysis showed that advanced age, female
      gender, hypoglycemic events, and hospitalization for glycemic decompensation were
      independently associated with a worse MPI score. CONCLUSION: Stratification of
      elderly diabetic patients using the MPI might help to identify those patients at
      highest risk who need better-tailored treatment.

PMID- 24689063
TI  - Integrative analysis of miRNA-mRNA and miRNA-miRNA interactions.
AB  - MicroRNAs (miRNAs) are small, noncoding regulatory molecules. They are involved
      in many essential biological processes and act by suppressing gene expression.
      The present work reports an integrative analysis of miRNA-mRNA and miRNA-miRNA
      interactions and their regulatory patterns using high-throughput miRNA and mRNA
      datasets. Aberrantly expressed miRNA and mRNA profiles were obtained based on
      fold change analysis, and qRT-PCR was used for further validation of deregulated
      miRNAs. miRNAs and target mRNAs were found to show various expression patterns.
      miRNA-miRNA interactions and clustered/homologous miRNAs were also found to
      contribute to the flexible and selective regulatory network. Interacting miRNAs
      (e.g., miRNA-103a and miR-103b) showed more pronounced differences in expression,
      which suggests the potential "restricted interaction" in the miRNA world. miRNAs
      from the same gene clusters (e.g., miR-23b gene cluster) or gene families (e.g.,
      miR-10 gene family) always showed the same types of deregulation patterns,
      although they sometimes differed in expression levels. These clustered and
      homologous miRNAs may have close functional relationships, which may indicate
      collaborative interactions between miRNAs. The integrative analysis of miRNA-mRNA
      based on biological characteristics of miRNA will further enrich miRNA study. 

PMID- 24689064
TI  - Composition, in vitro antioxidant and antimicrobial activities of essential oil
      and oleoresins obtained from black cumin seeds (Nigella sativa L.).
AB  - Gas chromatography-mass spectrometry (GC-MS) analysis revealed the major
      components in black cumin essential oils which were thymoquinone (37.6%) followed
      by p-cymene (31.2%), alpha-thujene (5.6%), thymohydroquinone (3.4%), and
      longifolene (2.0%), whereas the oleoresins extracted in different solvents
      contain linoleic acid as a major component. The antioxidant activity of essential
      oil and oleoresins was evaluated against linseed oil system at 200 ppm
      concentration by peroxide value, thiobarbituric acid value, ferric thiocyanate,
      ferrous ion chelating activity, and 1,1-diphenyl-2-picrylhydrazyl radical
      scavenging methods. The essential oil and ethyl acetate oleoresin were found to
      be better than synthetic antioxidants. The total phenol contents (gallic acid
      equivalents, mg GAE per g) in black cumin essential oil, ethyl acetate, ethanol,
      and n-hexane oleoresins were calculated as 11.47 +/- 0.05, 10.88 +/- 0.9, 9.68 +/
      0.06, and 8.33 +/- 0.01, respectively, by Folin-Ciocalteau method. The essential
      oil showed up to 90% zone inhibition against Fusarium moniliforme in inverted
      petri plate method. Using agar well diffusion method for evaluating antibacterial
      activity, the essential oil was found to be highly effective against Gram
      positive bacteria.

PMID- 24689065
TI  - Renal overexpression of atrial natriuretic peptide and hypoxia inducible factor
      1alpha as adaptive response to a high salt diet.
AB  - In the kidney, a high salt intake favors oxidative stress and hypoxia and causes
      the development of fibrosis. Both atrial natriuretic peptide (ANP) and hypoxia
      inducible factor (HIF-1alpha) exert cytoprotective effects. We tested the
      hypothesis that renal expression of ANP and HIF-1alpha is involved in a mechanism
      responding to the oxidative stress produced in the kidneys of rats chronically
      fed a high sodium diet. Sprague-Dawley rats were fed with a normal salt (0.4%
      NaCl) (NS) or a high salt (8% NaCl) (HS) diet for 3 weeks, with or without the
      administration of tempol (T), an inhibitor of oxidative stress, in the drinking
      water. We measured the mean arterial pressure (MAP), glomerular filtration rate
      (GFR), and urinary sodium excretion (UVNa). We evaluated the expression of ANP,
      HIF-1alpha, and transforming growth factor (TGF-beta1) in renal tissues by
      western blot and immunohistochemistry. The animals fed a high salt diet showed
      increased MAP and UVNa levels and enhanced renal immunostaining of ANP, HIF
      1alpha, and TGF-beta1. The administration of tempol together with the sodium
      overload increased the natriuresis further and prevented the elevation of blood
      pressure and the increased expression of ANP, TGF-beta1, and HIF-1alpha compared
      to their control. These findings suggest that HIF-1alpha and ANP, synthesized by
      the kidney, are involved in an adaptive mechanism in response to a sodium
      overload to prevent or attenuate the deleterious effects of the oxidative stress
      and the hypoxia on the development of fibrosis. 

PMID- 24689067
TI  - Low dose of valproate improves motor function after traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injuries (TBIs) are a major health care problem
      worldwide. Approximately 1.5 million new TBI cases occur annually in the United
      States, with mortality rates ranging between 35% and 40% in severe patients.
      Despite the incidence of these injuries and their substantial socioeconomic
      implications, no specific pharmacological intervention is available for clinical
      use. Several studies have indicated that 300 mg/kg or 400 mg/kg of valproate
      (VPA) exhibits neuroprotective effects in animal models. However, humans cannot
      tolerate high doses of VPA. This study aims to investigate whether 30 mg/kg of
      VPA administered to rats affects TBIs. METHODS: We used a rat model to test the
      effects of 30 mg/kg of VPA on TBIs. Molecular identifications for histone
      acetylation and phosphorylation of cAMP response element-binding protein (CREB)
      and phosphorylated extracellular signal regulated kinase (ERK) were performed.
      RESULTS: The results indicated that treating adult rats with VPA after TBIs
      significantly decreased the contusion volume and recovery of contusion-related
      skilled forelimb reaching deficits. Applying VPA also increased histone
      acetylation, p-ERK, and p-CREB expression in the brain. Furthermore, applying VPA
      reduced inflammation, glial fibrillary acidic protein activation, and apoptosis.
      Conclusion. This study found that 30 mg/kg of VPA assists in treating TBIs in rat
      models.

PMID- 24689066
TI  - The prevention of postmenopausal osteoporotic fractures: results of the Health
      Technology Assessment of a new antiosteoporotic drug.
AB  - OBJECTIVE: The Health Technology Assessment (HTA) approach was applied to
      denosumab in the prevention of osteoporotic fractures in postmenopausal women.
      METHOD: Epidemiological, clinical, technical, economic, organizational, and
      ethical aspects were considered. Medical electronic databases were accessed to
      evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact
      and a cost-effectiveness analyses were performed to assess economic implications.
      Clinical benefits and patient needs were considered with respect to
      organizational and ethical evaluation. RESULTS: In Italy around four millions
      women are affected by osteoporosis and have a higher risk for fractures with
      70,000 women being hospitalized every year. Bisphosphonates and strontium
      ranelate are recommended as first line treatment for the prevention of
      osteoporotic fractures. Denosumab is effective in reducing vertebral,
      nonvertebral, and hip/femoral fractures with an advantage of being administered
      subcutaneously every six months. The budget impact analysis estimated a reduction
      in costs for the National Health Service with the introduction of denosumab.
      Furthermore, the economic analysis demonstrated that denosumab is cost-effective
      in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be
      administered in outpatients by involving General Practitioners in the management.
      Ethical evaluation is positive because of its efficacy and compliance.
      CONCLUSION: Denosumab could add value in the prevention of osteoporotic
      fractures.

PMID- 24689069
TI  - Newborn screening: the genomic challenge.

PMID- 24689068
TI  - Comparative analysis of changes of myocardial angiogenesis and energy metabolism
      in postinfarction and diabetic damage of rat heart.
AB  - Comparative study of changes in myocardial activity of lactate dehydrogenase
      (LDH), succinate dehydrogenase (SDH), and capillary density distribution in the
      experimental models of diabetic and postinfarction damage of rat heart was
      performed. Data showed that decrease in LDH and SDH activities was observed in
      both pathologies which can suggest abnormal processes of glycolysis and oxidative
      phosphorylation in cardiac mitochondria. Activity of LDH and SDH in combined
      pathologies was comparative with the corresponding values of these parameters in
      control group. The authors hypothesize that these differences can be caused by
      specifics of myocardial vascularization. The results of the study showed that an
      increase in capillary density was found in all groups of rats with pathologies
      compared with control group. However, no significant differences in the intensity
      of angiogenesis processes were found between groups with pathologies. 

PMID- 24689070
TI  - Genetics and genomic medicine in Israel.

PMID- 24689071
TI  - SHOX gene and conserved noncoding element deletions/duplications in Colombian
      patients with idiopathic short stature.
AB  - SHOX gene mutations or haploinsufficiency cause a wide range of phenotypes such
      as Leri Weill dyschondrosteosis (LWD), Turner syndrome, and disproportionate
      short stature (DSS). However, this gene has also been found to be mutated in
      cases of idiopathic short stature (ISS) with a 3-15% frequency. In this study,
      the multiplex ligation-dependent probe amplification (MLPA) technique was
      employed to determine the frequency of SHOX gene mutations and their conserved
      noncoding elements (CNE) in Colombian patients with ISS. Patients were referred
      from different centers around the county. From a sample of 62 patients, 8.1%
      deletions and insertions in the intragenic regions and in the CNE were found.
      This result is similar to others published in other countries. Moreover, an
      isolated case of CNE 9 duplication and a new intron 6b deletion in another
      patient, associated with ISS, are described. This is one of the first studies of
      a Latin American population in which deletions/duplications of the SHOX gene and
      its CNE are examined in patients with ISS. 

PMID- 24689072
TI  - Novel IFT122 mutation associated with impaired ciliogenesis and cranioectodermal
      dysplasia.
AB  - Cranioectodermal dysplasia (CED) is a very rare autosomal recessive disorder
      characterized by a recognizable craniofacial profile in addition to ectodermal
      manifestations involving the skin, hair, and teeth. Four genes are known to be
      mutated in this disorder, all involved in the ciliary intraflagellar transport
      confirming that CED is a ciliopathy. In a multiplex consanguineous family with
      typical CED features in addition to intellectual disability and severe cutis
      laxa, we used autozygosity-guided candidate gene analysis to identify a novel
      homozygous mutation in IFT122, and demonstrated impaired ciliogenesis in patient
      fibroblasts. This report on IFT122 broadens the phenotype of CED and expands its
      allelic heterogeneity. 

PMID- 24689073
TI  - The pathogenicity scoring system for mitochondrial tRNA mutations revisited.
AB  - Confirming the pathogenicity of mitochondrial tRNA point mutations is one of the
      classical challenges in the field of mitochondrial medicine. In addition to
      genetic and functional studies, the evaluation of a genetic change using a
      pathogenicity scoring system is extremely useful to discriminate between disease
      causing mutations from neutral polymorphisms. The pathogenicity scoring system is
      very robust for confirming pathogenicity, especially of mutations that show
      impaired activity in functional studies. However, mutations giving normal results
      using the same functional approaches are disregarded, and this compromises the
      power of the system to rule out pathogenicity. We propose to include a new
      criterion in the pathogenicity scoring systems regarding mutations which fail to
      show any mitochondrial defect in functional studies. To evaluate this proposal we
      characterized two mutations, m.8296A>G and m.8347A>G, in the mitochondrial
      tRNA(L) (ys) gene (MT-TK) using trans-mitochondrial cybrid analysis. m.8347A>G
      mutation severely impairs oxidative phosphorylation, suggesting that it is highly
      pathogenic. By contrast, the behavior of cybrids homoplasmic for the m.8296A>G
      mutation is similar to cybrids containing wild-type mitochondrial DNA (mtDNA).
      The results indicate that including not only positive but also negative outcomes
      of functional studies in the scoring system is critical for facilitating the
      diagnosis of this complex group of diseases. 

PMID- 24689074
TI  - Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy
      number variants and a mosaic deletion.
AB  - Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder
      characterized by growth retardation, intellectual disability, upper limb
      abnormalities, hirsutism, and characteristic facial features. In this study we
      explored the occurrence of intragenic NIPBL copy number variations (CNVs) in a
      cohort of 510 NIPBL sequence-negative patients with suspected CdLS. Copy number
      analysis was performed by custom exon-targeted oligonucleotide array-comparative
      genomic hybridization and/or MLPA. Whole-genome SNP array was used to further
      characterize rearrangements extending beyond the NIPBL gene. We identified NIPBL
      CNVs in 13 patients (2.5%) including one intragenic duplication and a deletion in
      mosaic state. Breakpoint sequences in two patients provided further evidence of a
      microhomology-mediated replicative mechanism as a potential predominant
      contributor to CNVs in NIPBL. Patients for whom clinical information was
      available share classical CdLS features including craniofacial and limb defects.
      Our experience in studying the frequency of NIBPL CNVs in the largest series of
      patients to date widens the mutational spectrum of NIPBL and emphasizes the
      clinical utility of performing NIPBL deletion/duplication analysis in patients
      with CdLS. 

PMID- 24689075
TI  - Deciphering intrafamilial phenotypic variability by exome sequencing in a Bardet
      Biedl family.
AB  - Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by a wide range
      of clinical variability. The heterogeneity of this condition is reflected in the
      number of underlying gene defects and the epistatic interactions between the
      proteins encoded. BBS is generally inherited in an autosomal recessive trait.
      However, in some families, mutations across different loci interact to modulate
      the expressivity of the phenotype. In order to investigate the magnitude of
      epistasis in one BBS family with remarkable intrafamilial phenotypic variability,
      we designed an exome sequencing-based approach using SOLID 5500xl platform. This
      strategy allowed the reliable detection of the primary causal mutations in our
      family consisting of two novel compound heterozygous mutations in McKusick
      Kaufman syndrome (MKKS) gene (p.D90G and p.V396F). Additionally, exome sequencing
      enabled the detection of one novel heterozygous NPHP4 variant which is predicted
      to activate a cryptic acceptor splice site and is only present in the most
      severely affected patient. Here, we provide an exome sequencing analysis of a BBS
      family and show the potential utility of this tool, in combination with network
      analysis, to detect disease-causing mutations and second-site modifiers. Our data
      demonstrate how next-generation sequencing (NGS) can facilitate the dissection of
      epistatic phenomena, and shed light on the genetic basis of phenotypic
      variability. 

PMID- 24689076
TI  - Nemaline myopathy caused byTNNT1 mutations in a Dutch pedigree.
AB  - Nemaline myopathy (NM) is genetically heterogeneous disorder characterized by
      early onset muscular weakness and sarcoplasmatic or intranuclear inclusions of
      rod-shaped Z-disk material in muscle fibers. Thus far, mutations in seven genes
      have been identified as cause of NM. Only one singleTNNT1 nonsense mutation has
      been previously described that causes autosomal recessive NM in the old order
      Amish with a very specific clinical phenotype including rapidly progressive
      contractures. Here, we report a patient who is compound heterozygous for a
      c.309+1G>A mutation and an exon 14 deletion in theTNNT1 gene. This report
      confirms the specific clinical phenotype ofTNNT1 NM and documents two newTNNT1
      mutations outside the old order Amish. 

PMID- 24689077
TI  - Analysis of PRICKLE1 in human cleft palate and mouse development demonstrates
      rare and common variants involved in human malformations.
AB  - Palate development is shaped by multiple molecular signaling pathways, including
      the Wnt pathway. In mice and humans, mutations in both the canonical and
      noncanonical arms of the Wnt pathway manifest as cleft palate, one of the most
      common human birth defects. Like the palate, numerous studies also link different
      Wnt signaling perturbations to varying degrees of limb malformation; for example,
      shortened limbs form in mutations of Ror2,Vangl2 (looptail) and, in particular,
      Wnt5a. We recently showed the noncanonical Wnt/planar cell polarity (PCP)
      signaling molecule Prickle1 (Prickle like 1) also stunts limb growth in mice. We
      now expanded these studies to the palate and show that Prickle1 is also required
      for palate development, like Wnt5a and Ror2. Unlike in the limb, the
      Vangl2looptail mutation only aggravates palate defects caused by other mutations.
      We screened Filipino cleft palate patients and found PRICKLE1 variants, both
      common and rare, at an elevated frequency. Our results reveal that in mice and
      humans PRICKLE1 directs palate morphogenesis; our results also uncouple Prickle1
      function from Vangl2 function. Together, these findings suggest mouse and human
      palate development is guided by PCP-Prickle1 signaling that is probably not
      downstream of Vangl2. 

PMID- 24689078
TI  - Association study in three different populations between the GPR88 gene and major
      psychoses.
AB  - GPR88, coding for a G protein-coupled orphan receptor that is highly represented
      in the striatum, is a strong functional candidate gene for neuropsychiatric
      disorders and is located at 1p22-p21, a chromosomal region that we have
      previously linked to bipolar disorder (BD) in the Sardinian population. In order
      to ascertain the relevance of GPR88 as a risk factor for psychiatric diseases, we
      performed a genetic association analysis between GPR88 and BD in a sample of
      triads (patient and both parents) recruited in the Sardinian and the Palestinian
      population as well as between GPR88 and schizophrenia (SZ) in triads from the
      Xhosa population in South Africa. We found a positive association between GPR88
      and BD in the Sardinian and Palestinian triads. Moreover, we found a positive
      association between GPR88 and SZ in triads from the Xhosa population in South
      Africa. When these results were corrected for multiple testing, the association
      between GPR88 and BD was maintained in the Palestinian population. Thus, these
      results suggest that GPR88 deserves consideration as a candidate gene for
      psychiatric diseases and requires to be further investigated in other
      populations. 

PMID- 24689079
TI  - High frequency of exon 15 deletion in the FANCA gene in Tunisian patients
      affected with Fanconi anemia disease: implication for diagnosis.
AB  - Tunisian population is characterized by its heterogeneous ethnic background and
      high rate of consanguinity. In consequence, there is an increase in the frequency
      of recessive genetic disorders including Fanconi anemia (FA). The aim of this
      study was to confirm the existence of a founder haplotype among FA Tunisian
      patients and to identify the associated mutation in order to develop a simple
      tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA
      patients were investigated. All available family members were genotyped with four
      microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity
      mapping assigned 83 patients belonging to 62 families to the FA-A group. A common
      haplotype was shared by 42 patients from 26 families at a homozygous state while
      five patients from five families were heterozygous. Among them, 85% were from
      southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent
      probe amplification (MLPA) technique, we have also demonstrated that this
      haplotype is associated with a total deletion of exon 15 in FANCA gene.
      Identification of a founder mutation allowed genetic counseling in relatives of
      these families, better bone marrow graft donor selection and prenatal diagnosis.
      This mutation should be investigated in priority for patients originating from
      North Africa and Middle East. 

PMID- 24689080
TI  - Chromosomal microarray analysis as a first-tier clinical diagnostic test:
      Estonian experience.
AB  - Chromosomal microarray analysis (CMA) is now established as the first-tier
      cytogenetic diagnostic test for fast and accurate detection of chromosomal
      abnormalities in patients with developmental delay/intellectual disability
      (DD/ID), multiple congenital anomalies (MCA), and autism spectrum disorders
      (ASD). We present our experience with using CMA for postnatal and prenatal
      diagnosis in Estonian patients during 2009-2012. Since 2011, CMA is on the
      official service list of the Estonian Health Insurance Fund and is performed as
      the first-tier cytogenetic test for patients with DD/ID, MCA or ASD. A total of
      1191 patients were analyzed, including postnatal (1072 [90%] patients and 59 [5%]
      family members) and prenatal referrals (60 [5%] fetuses). Abnormal results were
      reported in 298 (25%) patients, with a total of 351 findings (1-3 per
      individual): 147 (42%) deletions, 106 (30%) duplications, 89 (25%) long
      contiguous stretches of homozygosity (LCSH) events (>5 Mb), and nine (3%)
      aneuploidies. Of all findings, 143 (41%) were defined as pathogenic or likely
      pathogenic; for another 143 findings (41%), most of which were LCSH, the clinical
      significance remained unknown, while 61 (18%) reported findings can now be
      reclassified as benign or likely benign. Clinically relevant findings were
      detected in 126 (11%) patients. However, the proportion of variants of unknown
      clinical significance was quite high (41% of all findings). It seems that our
      ability to detect chromosomal abnormalities has far outpaced our ability to
      understand their role in disease. Thus, the interpretation of CMA findings
      remains a rather difficult task requiring a close collaboration between
      clinicians and cytogeneticists. 

PMID- 24689081
TI  - High mutation detection rates in cerebral cavernous malformation upon stringent
      inclusion criteria: one-third of probands are minors.
AB  - Cerebral cavernous malformations (CCM) are prevalent vascular malformations
      occurring in familial autosomal dominantly inherited or isolated forms. Once CCM
      are diagnosed by magnetic resonance imaging, the indication for genetic testing
      requires either a positive family history of cavernous lesions or clinical
      symptoms such as chronic headaches, epilepsy, neurological deficits, and
      hemorrhagic stroke or the occurrence of multiple lesions in an isolated case.
      Following these inclusion criteria, the mutation detection rates in a consecutive
      series of 105 probands were 87% for familial and 57% for isolated cases. Thirty
      one novel mutations were identified with a slight shift towards proportionally
      more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%,
      CCM3: 22%). In-frame deletions and exonic missense variants requiring functional
      analyses to establish their pathogenicity were rare: An in-frame deletion within
      the C-terminal FERM domain of CCM1 resulted in decreased protein expression and
      impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20%
      of index cases carrying a CCM mutation were below age 10 and 33% below age 18
      when referred for genetic testing. Since fulminant disease courses during the
      first years of life were observed in CCM1 and CCM3 mutation carriers, predictive
      testing of minor siblings became an issue. 

PMID- 24689083
TI  - Geographical genetic variability: a factor to consider when assessing clinical
      implications of PRDM9.

PMID- 24689082
TI  - A massive parallel sequencing workflow for diagnostic genetic testing of mismatch
      repair genes.
AB  - The purpose of this study was to develop a massive parallel sequencing (MPS)
      workflow for diagnostic analysis of mismatch repair (MMR) genes using the GS
      Junior system (Roche). A pathogenic variant in one of four MMR genes, (MLH1,
      PMS2, MSH6, and MSH2), is the cause of Lynch Syndrome (LS), which mainly
      predispose to colorectal cancer. We used an amplicon-based sequencing method
      allowing specific and preferential amplification of the MMR genes including PMS2,
      of which several pseudogenes exist. The amplicons were pooled at different ratios
      to obtain coverage uniformity and maximize the throughput of a single-GS Junior
      run. In total, 60 previously identified and distinct variants (substitutions and
      indels), were sequenced by MPS and successfully detected. The heterozygote
      detection range was from 19% to 63% and dependent on sequence context and
      coverage. We were able to distinguish between false-positive and true-positive
      calls in homopolymeric regions by cross-sample comparison and evaluation of flow
      signal distributions. In addition, we filtered variants according to a predefined
      status, which facilitated variant annotation. Our study shows that implementation
      of MPS in routine diagnostics of LS can accelerate sample throughput and reduce
      costs without compromising sensitivity, compared to Sanger sequencing. 

PMID- 24689086
TI  - Rectal polyp caused by Schistosoma haematobium.

PMID- 24689087
TI  - Reversible acute duodenitis as a complication of endoscopic biliary stenting.

PMID- 24689088
TI  - Nonsteroidal anti-inflammatory drug (NSAID)-induced colopathy with diaphragm-like
      strictures.

PMID- 24689089
TI  - Adenocarcinoma of the right colon penetrating the liver.

PMID- 24689090
TI  - A typical case of Bouveret's syndrome, or not?

PMID- 24689091
TI  - The contribution of intrabolus pressure to symptoms induced by gastric banding.
AB  - BACKGROUND & AIMS: Mechanisms that ultimately lead to dysphagia are still not
      totally clear. Patients with laparoscopic gastric banding (LAGB) often complain
      about dysphagia, regurgitation and heartburn. Our aim was to evaluate the
      contribution of intrabolus pressure to symptoms of gastric banding. METHODS: This
      study investigated 30 patients with LAGB before and 3 months after conversion to
      Roux-en-Y gastric bypass (RYGB), evaluating symptoms with a 7-point-Likert-scale
      and esophageal peristalsis, esophageal bolus transit and intrabolus pressure
      changes using combined impedance-manometry. RESULTS: Conversion from LAGB to RYGB
      leads to a significant reduction in dysphagia (1.9 +/- 0.4 vs. 0.0 +/- 0.0; p<
      0.01) and regurgitation (4.2 +/- 0.4 vs. 0.1 +/- 0.1; p< 0.01) symptom scores.
      For liquid swallows we found a modest but significant correlation between the
      intensity of dysphagia and intrabolus pressure (r=0.11; p<0.05) and the intensity
      of regurgitation and intrabolus pressure for viscous swallows (r=0.12, p<0.05) in
      patients with LAGB. There was a significant (p< 0.05) reduction in intrabolus
      pressure at 5 cm above LES before (liquid 10.6 +/-1.0; viscous 13.5 +/- 1.5) and
      after (liquid 6.4 +/- 0.6; viscous 10.5 +/- 0.9) conversion from LAGB to RYGB.
      CONCLUSION: Current data suggest that intraesophageal pressure during bolus
      presence in the distal esophagus contributes to the development but not to the
      intensity of dysphagia and regurgitation.

PMID- 24689092
TI  - Barrett's esophagus and intestinal metaplasia of gastric cardia: prevalence,
      clinical, endoscopic and histological features.
AB  - BACKGROUND & AIMS: Over the past few decades, the incidence of adenocarcinomas of
      the gastroesophageal junction has rapidly increased. Barrett's esophagus is a
      risk factor for esophageal adenocarcinoma, but the role of intestinal metaplasia
      of the gastric cardia as a precursor in cardia-related cancer is controversial.
      The aims of the present study were to examine the prevalence of intestinal
      metaplasia in the gastroesophageal junction and to evaluate the clinical,
      endoscopical and histological features of patients with intestinal metaplasia in
      the gastric cardia and patients with Barrett's esophagus. METHODS: 286
      consecutive patients undergoing gastroduodenoscopy were enrolled in a prospective
      study. Biopsy specimens were performed in the distal esophagus, squamocolumnar
      junction, gastric cardia, gastric corpus and antrum. RESULTS: We identified 44
      patients (15.3%) with intestinal metaplasia in biopsies from gastric cardia and
      24 patients (8.3%) with Barrett's esophagus. Cardia intestinal metaplasia was
      significantly associated with older age (p=0.03), with intestinal metaplasia in
      the antrum (p=0.017) and H. pylori infection (p<0.0001). Severe chronic cardia
      inflammation increased the presence of cardia intestinal metaplasia 6.2 fold
      (OR=6.288; p<0.0001). Patients with Barrett's esophagus were predominantly men.
      Barrett's esophagus presence significantly correlated with reflux
      symptoms(p<0.0001), endoscopic esophagitis (p<0.0001) and hiatal hernia >2 cm
      (p=0.002). No patient had dysplasia in the gastroesophageal region. CONCLUSIONS:
      Presence of intestinal metaplasia at the gastroesophageal region correlated with
      reflux symptoms and endoscopic signs of reflux disease in patients with Barrett's
      esophagus and with H.pylori infection and distal intestinal metaplasia in
      patients with cardia intestinal metaplasia.

PMID- 24689093
TI  - Transnasal endoscopy is preferred by transoral endoscopy experienced patients.
AB  - BACKGROUND & AIMS: Both unsedated transoral endoscopy (TOE) and sedated TOE have
      some drawbacks in clinical practice. Unsedated transnasal endoscopy (TNE) has
      been suggested as an alternative to both methods. This study aimed to determine
      the advantages of TNE in patients who have previously undergone unsedated
      conventional TOE. METHODS: Patients who had received an unsedated TOE in the last
      12 months and were scheduled for a second upper endoscopy were included. They
      were randomized to undergo either unsedated TOE, using a standard endoscope, or
      unsedated TNE, using an ultrathin endoscope. Post-procedure, patients were asked
      to complete a questionnaire to assess pain, discomfort and acceptability of the
      procedure, and to compare the current procedure with their previous unsedated
      TOE. Endoscope insertion rate, procedure duration, and side-effects were
      recorded. RESULTS: Each group included 50 patients. With the exception of nasal
      pain, the tolerability and acceptance were significantly greater in the unsedated
      TNE group. Significantly more TNE patients (82%) found the current endoscopic
      procedure to be better than their previous TOE when compared with patients who
      had received a second TOE (12%). A repeat procedure was significantly more
      acceptable for TNE patients when compared to the TOE group (68% vs.16%). The
      duration of endoscopy was significantly shorter in TOE than in TNE (p<0.05).
      Endoscope insertion failed in 4% and mild epistaxis was observed in 4% of TNE
      patients. CONCLUSION: Unsedated TNE was better tolerated in endoscopy experienced
      patients when compared with unsedated TOE. The majority of patients found TNE
      more acceptable and preferable to TOE, suggesting that TNE should become a more
      common practice in clinics when applicable.

PMID- 24689094
TI  - Healthy PNPLA3 risk allele carriers present with unexpected body fat composition.
      A study of one thousand subjects.
AB  - INTRODUCTION: The common PNPLA3 (adiponutrin) variant p.I148M represents a major
      genetic driver of progression in non-alcoholic fatty liver disease (NAFLD). NAFLD
      is commonly associated with traits of the metabolic syndrome, therefore it is
      mostly suspected in obese individuals. Here, we investigate the association
      between the PNPLA3 variant and anthropometric traits in a cohort of healthy
      individuals. PATIENTS AND METHODS: We recruited 1,000 (500 females; age 18-66
      years) healthy blood donors. The PNPLA3 variant was genotyped using TaqMan
      assays. All individuals were phenotyped with respect to anthropometric
      characteristics. We also determined the percentage of total fat (F%) and active
      tissue (TA%) of body weight. RESULTS: Healthy carriers of the PNPLA3 [IM] and
      [MM] genotypes, although not differing in height from individuals with the
      genotype [II], displayed significantly lower body weight and lower BMI (both P =
      0.005), higher TA% (P = 0.03) but lower F% (P = 0.03) and smaller waist, chest
      and shin circumferences (all P < 0.05). Separate analysis for males and females
      demonstrated an association between the [IM] and [MM] genotypes and higher TA%
      but lower F% (P = 0.04) in females. In males, BMI and total weight were
      significantly (P = 0.04) lower among carriers of the [M] allele. DISCUSSION:
      Healthy individuals carrying the prosteatotic PNPLA3 allele p.I48M may be leaner
      as compared to the carriers of the common allele. Hence in clinical practice they
      might be overlooked since they do not necessarily present with the anthropometric
      characteristics commonly associated with severe hepatic steatosis.

PMID- 24689095
TI  - Nailfold capillaroscopy in primary biliary cirrhosis: a useful tool for the early
      diagnosis of scleroderma.
AB  - BACKGROUND & AIM: Primary biliary cirrhosis (PBC) is frequently associated with
      other autoimmune diseases, including systemic sclerosis (SSc). In the last years
      many efforts have been dedicated to the research of widely accepted criteria for
      the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC
      patients are lacking, our aim was to investigate its hitherto unknown prevalence
      in a large cohort of PBC patients. METHODS: We studied 80 PBC patients and 72
      patients with other chronic liver diseases. Diagnostic workup included research
      into signs of connective tissue disease, determination of autoantibody profile,
      and examination of capillary abnormalities through nailfold videocapillaroscopy.
      RESULTS: Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and
      5 (6.3%) had definite SSc. None of the patients in the control group were
      diagnosed either with early or definite SSc. No differences were observed in
      terms of aminotransferases, alkaline phosphatase, and liver function tests
      between PBC patients with and without associated SSc. CONCLUSIONS: Early SSc is
      significantly frequent in PBC patients. The detection of early SSc in PBC
      patients may lead to a prompt treatment of its complications, preventing
      inabilities and preserving the chance of liver transplantation.

PMID- 24689096
TI  - A real life boceprevir use in treatment-experienced HCV genotype 1 patients with
      advanced fibrosis.
AB  - BACKGROUND: A number of high quality randomized clinical trials examining the
      efficacy and safety of triple therapy in genotype-1 HCV-infected patients have
      been published. However, these trials included a small number of patients with
      advanced fibrosis, and selected a population different from that in real-world
      settings. AIM: To determine the efficacy of boceprevir, pegInterferon and
      ribavirin regimen in genotype-1 treatment-experienced HCV-infected patients with
      cirrhosis and bridging fibrosis in real-life setting. METHOD: 167 treatment
      experienced patients (85.6% relapsers) out of which 33.5% had cirrhosis, with a
      mean age of 52.6 years, registered in the Romanian Name Patient Program Database
      were included into the study. RESULTS: 16.7% of patients had a viral load >100
      IU/mL. Undetectable HCV RNA was encountered in 77.3% of patients at week 12.
      Multiple logistic regression analysis revealed the following independent
      predictors, measured at week 8, for an HCV RNA >=100 IU/mL at week 12 of triple
      therapy: alanine aminotransferase values (p=0.01), hemoglobin level (p=0.04) and
      <2 log drop of viral load (p<0.0001). A stopping score at 8 weeks was created as
      the sum of these 3 parameters, with a total of 4 possible points. AUROC of this
      score was 0.84, with a sensitivity of 75% and a specificity of 86.2%. CONCLUSION:
      Triple therapy in this cohort of real-life genotype-1 HCV-infected patients with
      advanced fibrosis showed robust early virological response (EVR) rates. A week 8
      model predicting lack of EVR was created, with good clinical utility that can be
      validated in prospective larger cohorts.

PMID- 24689097
TI  - Relationship between NT-proBNP and cardio-renal dysfunction in patients with
      advanced liver cirrhosis.
AB  - BACKGROUND & AIMS: ProBNP is a sensitive marker of cardiac dysfunction. We
      assessed the concentration of circulating NT-proBNP in patients with liver
      cirrhosis in various stages of the disease and its correlation with markers of
      cardiac and renal dysfunction and with markers of liver disease severity.
      PATIENTS AND METHODS: A number of 88 patients with liver cirrhosis were included
      in the study, divided into 3 groups: group 1--18 control patients without
      ascites; group 2--35 non-azotemic patients with ascites; group 3--35 patients
      with hepatorenal syndrome. The cardiac dysfunction was assessed by measuring the
      NT-proBNP serum levels and the QTc interval. The markers of renal dysfunction
      were the estimated glomerular filtration rates--formulas involving creatinine and
      serum cystatin C. The Child-Pugh score was used to assess the liver disease
      severity. RESULTS: The median NT-proBNP serum levels significantly increased in
      patients with advanced liver cirrhosis (group 3: 960 fmol/ml and group 2: 660
      fmol/ml) as compared to group 1 (435 fmol/ml) (p<0.05). A significant direct
      correlation was found between the NT-proBNP concentration and the QTc interval
      (r=0.540, p<0.001). The NT-proBNP levels also correlated with the Child-Pugh
      score (r=0.501, p<0.01), proving the link between the cardiac dysfunction and the
      liver disease severity. The cardio-renal interrelation is supported by the
      relationship between the NT-proBNP concentration and the estimated clearances.
      CONCLUSION: The high NT-proBNP levels in patients with advanced cirrhosis
      indicate the presence of cardiac dysfunction, which has a role in the
      pathogenesis of the hepatorenal syndrome.

PMID- 24689098
TI  - Characterization of focal liver lesions using contrast enhanced ultrasound as a
      first line method: a large monocentric experience.
AB  - AIM: To present a large monocentric experience in the characterization of focal
      liver lesions (FLLs) using Contrast Enhanced Ultrasound (CEUS). METHOD: A
      retrospective study was performed in the Gastroenterology and Hepatology
      Department, Timisoara, including 1100 patients with 1329 FLLs evaluated between
      September 2009 and January 2013. A CEUS examination was considered conclusive if
      the FLL respected the typical enhancement pattern as described in the EFSUMB
      Guidelines. RESULTS: From the 1329 FLLs, CEUS was conclusive for a specific
      pathology in 1102 cases (82.9%). For the differentiation of benign/malignant
      lesions, CEUS reached a conclusive diagnosis in 1196 (90%) cases. The percentage
      of conclusive CEUS examinations was significantly higher in patients without
      chronic liver disease as compared with those with chronic hepatopathies: 87.3%
      vs. 74.4% (p<0.0001). CONCLUSION: CEUS patterns of enhancement fell into clear
      cut specific diagnostic patterns in 83% of the FLLs discovered by US, and into
      clear cut benign versus malignant patterns in 90% of the cases. For this reason,
      we can strongly recommend CEUS as a first line imaging method to characterize
      FLLs found at US, at least in centers with a good experience in CEUS.

PMID- 24689099
TI  - Scientific publications on portal vein thrombosis and Budd-Chiari syndrome: a
      global survey of the literature.
AB  - BACKGROUND & AIMS: Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS)
      are two rare vascular disorders of the liver that can lead to life-threatening
      complications. We conducted a global survey to systematically analyze the
      scientific publications in the fields of PVT and BCS. METHODS: All papers
      regarding PVT and BCS were identified via the PubMed, EMBASE, and Cochrane
      library databases. The publication year, country, type of paper, study design,
      and number of citations were summarized. Good quality papers were defined as
      those in which a high proportion of homogeneous patients with BCS and/or PVT was
      observed. RESULTS: We identified 6691 and 4325 papers regarding PVT and BCS,
      respectively. The number of papers gradually increased over time. Researchers
      from the USA published the greatest number of papers (PVT: n=1418; BCS: n=888).
      Clinical studies were the most common type of paper (PVT: n=5395; BCS n=3171),
      but fewer than half of these observed more than 10 patients (PVT: n=2667/5395;
      BCS: n=1092/3171). Furthermore, fewer than half of the clinical studies with more
      than 10 patients were of good quality (PVT: 976/2667; BCS: 466/1092). According
      to the study design, the good quality papers were classified as cohort studies
      (PVT: n=865; BCS: n=421), case-control studies (PVT: n=98; BCS: n=45), and
      randomized controlled trials (PVT: n=13; BCS: n=0). The 5 most frequently cited
      original articles and guidelines/consensuses were also listed. CONCLUSIONS:
      Despite an increase in the number of papers regarding PVT and BCS over time, most
      of the papers had a small sample size, suggesting the necessity of large cohort
      studies or randomized controlled trials.

PMID- 24689100
TI  - Metabolic syndrome, insulin resistance, circadian disruption, antioxidants and
      pancreatic carcinoma: an overview.
AB  - The incidence and number of deaths caused by pancreatic tumours have been
      gradually rising, while the incidence and mortality of other common cancers have
      been declining. Risk factors for this malignant disease include cigarette
      smoking, family history of chronic pancreatitis, advancing age, male sex,
      diabetes mellitus, obesity, non-0 blood group, a high-fat diet, alcohol
      consumption and possibly Helicobacter pylori and hepatitis B virus infections.
      Metabolic diseases have become the leading cause of death in many countries. Our
      paper serves as a focused and updated discussion about the development of novel
      preventive strategies for this deadly disease. 

PMID- 24689102
TI  - Benefits of curing hepatitis C infection.
AB  - The hepatitis C virus (HCV) infection is one of the most important chronic viral
      infections worldwide and affects 3% of the world population, approximately 170
      200 million people. The consequences of chronic infection are liver cirrhosis and
      hepatocellular carcinoma, which develop in 20-30% of the patients, leading to
      hepatic failure, need for liver transplantation and death. The hepatitis C virus
      is a RNA virus that is prevalent worldwide and is classified by the World Health
      Organization (International Agency for Research on Cancer) as one of the six
      oncogenic viruses. Hepatocellular carcinoma is one of the most important cancers
      and is fifth worldwide, but third in men in terms of mortality. Hepatitis C kills
      approximately 350,000 people every year, surpassing HIV infection in many
      countries as a cause of death. Hepatitis C virus can kill in different ways: it
      can cause cirrhosis, cancer or severe liver disease in people co-infected with
      HIV. Hepatitis C treatment started in the mid 1980s with a 6% efficacy rate among
      patients taking thrice-weekly injections of human interferon. This therapy had
      numerous side effects. The efficacy of hepatitis C treatment has increased, and
      currently, the efficacy of the so-called direct antiviral agents (DAAs) is 80
      90%. The benefits of a cure are enormous and include a lifetime negative serum
      HCV RNA, disappearance of HCV in the liver, regression of cirrhosis, decreased
      risk of developing hepatocellular carcinoma, disappearance of oesophageal
      varices, no more risk of HCV transmission to sexual partners or children, and
      increased survival. At present, hepatitis C can be considered a curable disease. 

PMID- 24689101
TI  - Recreational drugs: a new health hazard for patients with concomitant chronic
      liver diseases.
AB  - Our purpose in this article is to review the effects of recreational drugs, used
      either on their own but principally combined with alcohol consumption, in
      determining hepatic injury or influencing the evolution of some chronic diseases
      of the liver, specifically HCV infection and NAFLD. A deleterious role of daily
      use of recreational drugs, in particularly cannabis, has been shown to
      demonstrate clearly a rapid progression of fibrosis and steatosis, leading to a
      major severity in patients with chronic hepatitis C. On the other hand, the
      effects of the misuse of these substances on NAFLD, the main obesity-related
      comorbidity, leading to addiction, is still to be elucidated even though some
      clues to the recreational drugs hepatotoxicity are already present in the
      literature. This short review aims at raising awareness about this topic. 

PMID- 24689103
TI  - Unexpected Peutz-Jeghers syndrome in an adult presenting with intermittent upper
      intestinal obstruction. A case report.
AB  - Peutz-Jeghers syndrome is an autosomal dominant inherited disease, belonging to
      the hamartomatous polyposis syndromes. It is characterized by multiple
      hamartomatous polyps of the gastrointestinal tract associated with oral and anal
      mucocutaneous pigmentations. We report the case of an adult patient diagnosed
      with an atypical form of Peutz-Jeghers syndrome, thereby emphasizing the
      different possible syndrome phenotypes and the difficulty of their diagnosis. 

PMID- 24689104
TI  - Simultaneous occurrence of two rare diseases: actinomycosis and melanoma of the
      rectum.
AB  - The simultaneous occurrence of two rare conditions in a single patient is
      uncommon. We report the case of a patient with rectal actinomycosis covering an
      anorectal melanoma (both infrequent conditions), the last one being later
      recognized, only after surgical excision. We underline here the role of thinking
      "outside the box" when an unusual situation is experienced. 

PMID- 24689105
TI  - The epidemiology of Clostridium difficile infection in Romania: what we know, or
      do not know and why?

PMID- 24689106
TI  - Reply: To PMID 24369321.

PMID- 24689107
TI  - Fibrin-glue-sealed liver biopsy: indications, complications and results.

PMID- 24689108
TI  - Increased levels of serum amyloid A during the early phase of hepatitis C
      treatment with interferon are associated with sustained virologic response - a
      pilot study.

PMID- 24689109
TI  - Tumor characteristics and surgical therapy influence the outcome of
      gastrointestinal stromal tumors.

PMID- 24689110
TI  - Is there a role for chromoendoscopy in the diagnosis of coeliac disease?

PMID- 24689111
TI  - Bladder cancer.  Spot it early, follow it closely.

PMID- 24689112
TI  - Health tips.  Optimal hospital recovery.

PMID- 24689113
TI  - Mayo develops incision-free surgery for tennis elbow.

PMID- 24689114
TI  - Pelvic organ prolapse.  Deciding on surgery.

PMID- 24689115
TI  - Calories and weight loss. Complicated, yet simple.

PMID- 24689116
TI  - Fallen arches.  Beware the arch enemy.

PMID- 24689117
TI  - I have a fungal toenail infection. My doctor says treatment typically takes
      several months, and even then, a cure isn't guaranteed. I just assumed there
      would be some kind of medicine to take that would get rid of the problem. Is it
      really that hard to treat these infections?

PMID- 24689118
TI  - What is walking pneumonia? How is it different from other types of pneumonia?

PMID- 24689119
TI  - Eponymic infections.

PMID- 24689120
TI  - Year-round heartworm prevention.

PMID- 24689121
TI  - Veterinary economics  a priority in 2014. Leadership conference sets the stage
      for upcoming AVMA initiatives.

PMID- 24689122
TI  - State innovators: many of the elements in the Affordable Care Act were developed
      and already being used in the states.

PMID- 24689123
TI  - Delivering good news: the U.S. teen birth rate has fallen by more than half over
      the past two decades, but it's still higher than desirable.

PMID- 24689124
TI  - What states are doing to simplify health plan choice in the insurance
      marketplaces.
AB  - The new health insurance marketplaces aim to improve consumers' purchasing
      experiences by setting uniform coverage levels for health plans and giving them
      tools to explore their options. Marketplace administrators may choose to limit
      the number and type of plans offered to further simplify consumer decision
      making. This issue brief examines the policies set by some state-based
      marketplaces to simplify plan choices: adopting a meaningful difference standard,
      limiting the number of plans or benefit designs insurers may offer, or requiring
      standardized benefit designs. Eleven states and the District of Columbia took one
      or more of these actions for 2014, though their policies vary in terms of their
      prescriptiveness. Tracking the effects of these different approaches will enhance
      understanding of how best to enable consumers to make optimal health insurance
      purchasing decisions and set the stage for future refinements.

PMID- 24689125
TI  - Is routine screening chest radiography necessary for admission into our tertiary
      institutions in Nigeria?

PMID- 24689126
TI  - Authors' response.

PMID- 24689127
TI  - The all seeing eye?

PMID- 24689128
TI  - Orientation contrast and entropy contrast in the genesis of subjective contours
      along thin lines.
AB  - Subjective contours are widely considered to be an aspect of the perception of
      occlusion, but considerations of occlusion do not always drive predictions of
      their strength. Occluding surfaces have no necessary relationship to the contours
      they occlude, yet it is commonly predicted that subjective contours will be
      strongest for inducer alignments that are orthogonal to inducer orientations. In
      several papers we have proposed that a lack of relationship between inducers and
      their alignment promotes seeing subjective contours. We explore this further here
      using horizontal or near-horizontal thin-line inducers arranged vertically with
      linearly aligned terminations along central gaps. Subjective contour strength was
      measured using the method of paired comparison in two experiments. The weakest
      subjective contours were found when the gap was orthogonal to the inducers and
      parallel to the outer edges of the line set. Subjective contours were
      strengthened by orientation contrast, defined either as a nonorthogonal
      relationship between the gap and the inducers or as nonparallelism between the
      gap and the outer alignments of the inducers. The effect was replicated at both
      high and low line densities. We also confirmed a strong effect of high inducer
      entropy (variations in inducer orientation and separation) with thin-line
      inducers. The results support the view that the lack of a relationship of
      alignments to what is aligned is a major determinant of subjective contour
      strength.

PMID- 24689129
TI  - Picture surface illusion: small effects on a major axis.
AB  - Perception of 2-D ellipses on a picture surface is inaccurate-if the ellipses
      depict circles that are tilted in 3-D, receding from the viewer (Hammad, Kennedy,
      Juricevic, & Rajani, 2008a, Perception, 37, 504-510). Notably, the minor axis of
      the ellipse is seen as larger than is true. This illusory effect could be due to
      the simultaneous presence of optical information for the 2-D ellipse and optical
      information for the 3-D tilted circle. The optical information for the circle may
      bias vision's use of the optical information for the ellipse. This theory
      predicts that illusory effects should occur on the major axis as well as the
      minor axis; but, we argue, the major axis effect should be smaller than the minor
      axis effect. We confirm the prediction. Observers looked at target ellipses
      depicting tops of tilted cylinders. In one experiment observers chose a match for
      the target from choice sets of seven 2-D ellipses. In the second, observers used
      the method of adjustment. Both axes were overestimated, the minor axis more than
      the major, as the theory suggested. We point out that the relative size of the
      effects matters to the theory, and so the small effect counts for a lot.

PMID- 24689130
TI  - The influence of feature conjunction on object inversion and conversion effects.
AB  - The face inversion effect is considered by some as a marker ofholistic or
      configural processing. In an effort to understand the relations between object
      orientation and the use of configuration for recognition, we explored the extent
      to which the combination of information across discrete, spatially separated
      object features contributed to the impact of transforming the orientation of
      faces and other objects. Subjects performed a matching task on four different
      sets of faces and novel objects. For two of the sets (diagnostic), the match
      could be made based on information contained in a single feature. For the
      remaining two sets (conjunction and disjunction), the information useful for
      successful matching was divided between two spatially separated features (at the
      top and at the bottom of the object). For OR disjunctions the top and bottom
      features provided redundant information such that subjects could rely on either
      the top or the bottom feature, whereas for AND conjunctions the top and bottom
      features provided unique information such that subjects needed to use both the
      top and the bottom features. Experiment 1 assessed the cost of inversion on these
      stimulus sets with the typical inversion task, where both study and test stimuli
      were presented in the same orientation. Consistent with previous work,
      significant inversion effects were found for all of the face sets, but none of
      the novel object sets. Experiment 2 assessed the cost of 'conversion'--that is,
      the effect of transforming the orientation of the stimulus between study and
      test. Consistent with previous work, significant conversion effects were found
      for all face sets; however, a significant conversion effect was also found for
      the AND novel set. That only the AND novel set was significant suggests that
      conversion effects are reliant on combination of information across features,
      which is compromised when the stimulus configuration is altered between study and
      test. The results suggest that configural processes, like those purportedly used
      for face recognition, may be domain-general processes that can also be recruited
      strategically with other types of objects.

PMID- 24689131
TI  - Measuring the effects through time of the influence of visuomotor and
      visuotactile synchronous stimulation on a virtual body ownership illusion.
AB  - Previous studies have examined the experience of owning a virtual surrogate body
      or body part through specific combinations of cross-modal multisensory
      stimulation. Both visuomotor (VM) and visuotactile (VT) synchronous stimulation
      have been shown to be important for inducing a body ownership illusion, each
      tested separately or both in combination. In this study we compared the relative
      importance of these two cross-modal correlations, when both are provided in the
      same immersive virtual reality setup and the same experiment. We systematically
      manipulated VT and VM contingencies in order to assess their relative role and
      mutual interaction. Moreover, we present a new method for measuring the induced
      body ownership illusion through time, by recording reports of breaks in the
      illusion of ownership ('breaks') throughout the experimental phase. The balance
      of the evidence, from both questionnaires and analysis of the breaks, suggests
      that while VM synchronous stimulation contributes the greatest to the attainment
      of the illusion, a disruption of either (through asynchronous stimulation)
      contributes equally to the probability of a break in the illusion.

PMID- 24689132
TI  - Attractiveness difference magnitude affected by context, range, and
      categorization.
AB  - Previous studies have shown that, when subjects view hedonically positive stimuli
      followed by stimuli oflesser hedonic value, their preference between the stimuli
      oflesser hedonic value decreases. This is hedonic condensation. In addition, its
      opposite, hedonic expansion, occurs when subjects view less hedonically positive
      stimuli followed by more hedonically positive stimuli. Experiment 1 showed both
      hedonic condensation and expansion in subjects who viewed pictures of
      unattractive and moderately attractive faces. Experiment 2 showed that, when
      subjects were instructed to view the stimuli as coming from two different groups,
      hedonic expansion but not hedonic condensation was eliminated. Experiment 3
      showed that increasing the attractiveness difference between the attractive and
      unattractive faces eliminated all effects of context on subjects' attractiveness
      difference judgments. Experiment 4 showed that forcing subjects to categorize the
      extremely attractive and unattractive faces into the same group resulted in
      hedonic expansion among attractive faces but not condensation among the
      unattractive faces. These results suggest that, as hedonic contrast changes the
      hedonic values of stimuli, it also changes the attention paid to those stimuli,
      thereby altering the degree of preference between them. Manipulations that
      prevent a shift in hedonic value also block a shift in the magnitude of the
      preference judgments.

PMID- 24689133
TI  - How does vibration reduce pain?
AB  - Cutaneous vibration is able to reduce both clinical and experimental pain, an
      effect called vibratory analgesia. The traditional explanation for this
      phenomenon is that it is mediated by lateral inhibition at the segmental (spinal
      cord) level, in pain-coding cells with center-surround receptive fields. We
      evaluated this hypothesis by testing for two signs of lateral inhibition-namely
      (1) an effect of the distance between the noxious and vibratory stimuli and (2)
      an inhibition-induced shift in the perceived location of the noxious stimulus.
      The experiment involved continuous ratings of the pain from pressure applied to
      the back of a finger, alone and in the presence of vibration delivered to sites
      on the palm of the hand both near to and far from the site of painful
      stimulation. Neither prediction of the segmental hypothesis was supported. There
      was also little evidence to support the view (widely held by subjects) that
      distraction is the primary mechanism of vibratory analgesia. The results are more
      consistent with a recently proposed theory of interactions between two cortical
      areas that are primarily involved in coding pain and touch, respectively.

PMID- 24689134
TI  - Bilateral symmetry and perceptual reversals.
AB  - Imposition of patterns varying in symmetry about the observer's median plane on a
      reversible figure affects duration for which each of the fluctuating percepts is
      experienced. Symmetry of the imposed patterns is associated with lesser
      difference between the two durations. This effect is particularly pronounced when
      the patterns are enantiomorphic and therefore jointly form a symmetrical pattern,
      but is also present when the patterns are symmetrical but unrelated.

PMID- 24689135
TI  - Looking at a blurry old family photo? Zoom out!
AB  - We investigated recognition of blurry faces and whether viewing size affects
      identification of such severely degraded images. Despite the common belief that
      face perception relies on middle spatial frequencies, the critical spatial
      frequency band for face recognition is not fixed but rather depends on size. This
      is especially pronounced at small sizes, where observers choose to utilize lower,
      rather than middle, frequencies to identify a face. Here we assessed recognition
      of identity via a novel use of the face adaptation paradigm. We examined face
      identity aftereffects of blurry and intact adaptors at two sizes. Intact adaptors
      induced significant aftereffects regardless of size. Small, but not large, blurry
      adaptors produced aftereffects despite the fact that both contained exactly the
      same level of facial detail. This suggests an inability to utilize low-frequency
      information for perceiving identity in large faces. We conclude that (1) size is
      a key factor in human face recognition processes and (2) coarse facial images are
      better recognized at small sizes.

PMID- 24689136
TI  - Neanderthal paintings? Production of prototypical human (Homo sapiens) faces
      shows systematic distortions.
AB  - People's sketches of human faces seem to be systematically distorted: the eye
      position is always higher than in reality. This bias was experimentally analyzed
      by a series of experiments varying drawing conditions. Participants either drew
      prototypical faces from memory (studies 1 and 2: free reconstruction; study 3:
      cued reconstruction) or directly copied average faces (study 4). Participants
      consistently showed this positioning bias, which is even in accord with facial
      depictions published in influential research articles by famous face researchers
      (study 5). We discuss plausible explanations for this reliable and stable bias,
      which is coincidentally similar to the morphology of Neanderthals.

PMID- 24689137
TI  - Cross-ecosystem impacts of stream pollution reduce resource and contaminant flux
      to riparian food webs.
AB  - The effects of aquatic contaminants are propagated across ecosystem boundaries by
      aquatic insects that export resources and contaminants to terrestrial food webs;
      however, the mechanisms driving these effects are poorly understood. We examined
      how emergence, contaminant concentration, and total contaminant flux by adult
      aquatic insects changed over a gradient of bioavailable metals in streams and how
      these changes affected riparian web-building spiders. Insect emergence decreased
      97% over the metal gradient, whereas metal concentrations in adult insects
      changed relatively little. As a result, total metal exported by insects (flux)
      was lowest at the most contaminated streams, declining 96% among sites. Spiders
      were affected by the decrease in prey biomass, but not by metal exposure or metal
      flux to land in aquatic prey. Aquatic insects are increasingly thought to
      increase exposure of terrestrial consumers to aquatic contaminants, but stream
      metals reduce contaminant flux to riparian consumers by strongly impacting the
      resource linkage. Our results demonstrate the importance of understanding the
      contaminant-specific effects of aquatic pollutants on adult insect emergence and
      contaminant accumulation in adults to predict impacts on terrestrial food webs.

PMID- 24689138
TI  - Advancing the use of local ecological knowledge for assessing data-poor species
      in coastal ecosystems.
AB  - Many of the world's most vulnerable and rapidly changing ecosystems are also
      among the most data-poor, leading to an increased interest in use of local
      ecological knowledge (LEK) to document long-term environmental change. The
      integration of multiple knowledge sources for assessing species abundance and
      distribution has gained traction over the past decade as a growing number of case
      studies show concordance between LEK and scientific data. This study advances the
      use of quantitative approaches for synthesizing LEK by presenting a novel
      application of bootstrapping and statistical modeling to evaluate variance in
      ecological observations of fisheries practitioners. We developed an historical
      record of abundance for 22 marine species in Puget Sound, Washington (USA), using
      LEK, and we quantified variation in perceptions of abundance trends among
      fishers, divers, and researchers. These individuals differed in aspects of their
      information environments, which are characterized by how, when, and where an
      individual has acquired ecological information. Abundance trends derived from
      interviews suggest that populations of long-lived rockfishes (Sebastes spp.) have
      been in decline since at least the 1960s and that three rockfishes protected
      under the Endangered Species Act were perceived as relatively less abundant than
      other species. Differences in perception of rockfish abundance trends among age
      groups were consistent with our hypothesis that the reported magnitude of decline
      in abundance would increase with age, with younger respondents more likely to
      report high abundance than older individuals across all periods. Temporal
      patterns in the mean and variance of reported rockfish abundance indices were
      qualitatively similar between fishers and researchers; however, fishers reported
      higher indices of abundance than researchers for all but one rockfish species.
      The two respondent groups reported similar changes in rockfish abundance from the
      1940s to 2000s, except for two recreationally valuable species that fishers
      perceived as having undergone greater declines than perceived by researchers.
      When aggregated at appropriate spatial-temporal scales and in a culturally
      appropriate manner, observations of resource users are a valuable source of
      ecological information. Continued development of creative analytical tools for
      synthesizing multiple knowledge sources will be essential for advancing the
      formal use of LEK in assessments of marine species.

PMID- 24689139
TI  - Beyond connectivity: how empirical methods can quantify population persistence to
      improve marine protected-area design.
AB  - Demographic connectivity is a fundamental process influencing the dynamics and
      persistence of spatially structured populations. Consequently, quantifying
      connectivity is essential for properly designing networks of protected areas so
      that they achieve their core ecological objective of maintaining population
      persistence. Recently, many empirical studies in marine systems have provided
      essential, and historically challenging to obtain, data on patterns of larval
      dispersal and export from marine protected areas (MPAs). Here, we review the
      empirical studies that have directly quantified the origins and destinations of
      individual larvae and assess those studies' relevance to the theory of population
      persistence and MPA design objectives. We found that empirical studies often do
      not measure or present quantities that are relevant to assessing population
      persistence, even though most studies were motivated or contextualized by MPA
      applications. Persistence of spatial populations, like nonspatial populations,
      depends on replacement, whether individuals reproduce enough in their lifetime to
      replace themselves. In spatial populations, one needs to account for the effect
      of larval dispersal on future recruitment back to the local population through
      local retention and other connectivity pathways. The most commonly reported
      descriptor of larval dispersal was the fraction of recruitment from local origin
      (self-recruitment). Self-recruitment does not inform persistence-based MPA design
      because it is a fraction of those arriving, not a fraction of those leaving
      (local retention), so contains no information on replacement. Some studies
      presented connectivity matrices, which can inform assessments of persistence with
      additional knowledge of survival and fecundity after recruitment. Some studies
      collected data in addition to larval dispersal that could inform assessments of
      population persistence but which were not presented in that way. We describe how
      three pieces of empirical information are needed to fully describe population
      persistence in a network of MPAs: (1) lifetime fecundity, (2) the proportion of
      larvae that are locally retained (or the full connectivity matrix), and (3)
      survival rate after recruitment. We conclude by linking theory and data to
      provide detailed guidance to empiricists and practitioners on field sampling
      design and data presentation that better informs the MPA objective of population
      persistence.

PMID- 24689140
TI  - Effect of eastern oysters (Crassostrea virginica) on sediment carbon and nitrogen
      dynamics in an urban estuary.
AB  - Oyster reefs have declined globally. Interest in their restoration has motivated
      research into oyster-mediated ecosystem services including effects on
      biodiversity, filtration, and nitrogen (N) cycling. Recent evidence suggests
      oysters may promote denitrification, or anaerobic respiration of nitrate (NO3-)
      into di-nitrogen gas, via benthic deposition of carbon (C) and N-rich
      biodeposits. However, the mechanisms whereby biodeposits promote N
      transformations prerequisite to denitrification (e.g., mineralization and
      nitrification) are unclear. Previous research has also not measured oysters'
      influence on N cycling in urbanized areas. In May 2010 we deployed eastern
      oysters (Crassostrea virginica) in mesh cages above sand-filled boxes at four
      sites across a nutrient gradient in Jamaica Bay, New York City (New York, USA).
      Oysters were arranged at four densities: 0, 40, 85, and 150 oysters/m2. For 17
      months we measured water-column nutrients and chlorophyll a, every two weeks to
      monthly. Every two months we measured sediment ash-free dry mass (AFDM),
      exchangeable ammonium (NH4+), ammonification, nitrification, denitrification
      potential (DNP), and NO3- and C limitation of DNP. Oysters increased sediment
      AFDM at three of four sites, with the greatest increase at high density. Oysters
      did not affect any N pools or transformations. However, variation among sites and
      dates illustrated environmental drivers of C and N biogeochemistry in this urban
      estuary. Overall, nitrification was positively related to net ammonification,
      water column NH4+, and sediment NH4+, but was not correlated with DNP.
      Denitrification was consistently and strongly NO3- limited, while C was not
      limiting or secondarily limiting. Therefore, the oyster-mediated increase in AFDM
      did not affect DNP because C was not its primary driver. Also, because DNP was
      unrelated to nitrification, it is unlikely that biodeposit N was converted to NO3
      for use as a denitrification substrate. Predicting times or sites where
      denitrification is driven by the C and N species originating from oyster
      biodeposits remains a challenge under eutrophic conditions. Towards this goal, we
      synthesized our conclusions with literature predictions in a conceptual model for
      pathways whereby oysters might influence C and N dynamics differently in
      oligotrophic relative to eutrophic ecosystems.

PMID- 24689141
TI  - Congruence in demersal fish, macroinvertebrate, and macroalgal community turnover
      on shallow temperate reefs.
AB  - To support coastal planning through improved understanding of patterns of biotic
      and abiotic surrogacy at broad scales, we used gradient forest modeling (GFM) to
      analyze and predict spatial patterns of compositional turnover of demersal
      fishes, macroinvertebrates, and macroalgae on shallow, temperate Australian
      reefs. Predictive models were first developed using environmental surrogates with
      estimates of prediction uncertainty, and then the efficacy of the three
      assemblages as biosurrogates for each other was assessed. Data from underwater
      visual surveys of subtidal rocky reefs were collected from the southeastern
      coastline of continental Australia (including South Australia and Victoria) and
      the northern coastline of Tasmania. These data were combined with 0.01 degree
      resolution gridded environmental variables to develop statistical models of
      compositional turnover (beta diversity) using GFM. GFM extends the machine
      learning, ensemble tree-based method of random forests (RF), to allow the
      simultaneous modeling of multiple taxa. The models were used to generate
      predictions of compositional turnover for each of the three assemblages within
      unsurveyed areas across the 6600 km of coastline in the region of interest. The
      most important predictor for all three assemblages was variability in sea surface
      temperature (measured as standard deviation from measures taken interannually).
      Spatial predictions of compositional turnover within unsurveyed areas across the
      region of interest were remarkably congruent across the three taxa. However, the
      greatest uncertainty in these predictions varied in location among the different
      assemblages. Pairwise congruency comparisons of observed and predicted turnover
      among the three assemblages showed that invertebrate and macroalgal biodiversity
      were most similar, followed by fishes and macroalgae, and lastly fishes and
      invertebrate biodiversity, suggesting that of the three assemblages, macroalgae
      would make the best biosurrogate for both invertebrate and fish compositional
      turnover.

PMID- 24689142
TI  - How much is too much? Identifying benchmarks of adverse effects of macroalgae on
      the macrofauna in intertidal flats.
AB  - Eutrophication, defined as the accumulation of organic matter typically in
      response to anthropogenically enhanced nutrient inputs, often takes the form of
      macroalgal blooms in shallow estuaries and causes a cascade of adverse ecosystem
      effects. Confidence in the use of macroalgae as an indicator of eutrophication in
      estuaries is limited by the lack of quantitative data on thresholds of adverse
      effects. Field experiments can provide "benchmarks" of no effect or adverse
      effects that can be used to validate thresholds derived statistically from field
      data. To determine a benchmark of adverse effects of macroalgal abundance on
      macrobenthic faunal communities in intertidal flats, experiments were conducted
      in two sites in Bodega Harbor (BOD) and two sites in Upper Newport Bay (UNB),
      California, USA. At each site, 24 cages maintained six treatments of macroalgae
      for eight weeks, with mat depths of 0, 1.0, 1.5, 2.5, 3.5, and 5.0 cm composed
      mostly of bloom-forming green macroalgae in the genus Ulva. Every two weeks,
      cores of sediment (10 cm deep) were collected, and macrofauna were quantified.
      Mats 1 cm deep, equivalent to a biomass of 110-120 g dry mass (dm)/m2 or 840-930
      g wet mass/m2, resulted in the reduction of macrofaunal abundance by at least 67%
      and species richness by at least 19% within two weeks at three of four sites.
      Loss was attributed to the decline of key functional groups. Surface-deposit
      feeders were eliminated from one site at BOD within four weeks and at one site in
      UNB within six weeks, while 1-cm mats negatively affected suspension feeders and
      herbivores in the second site at BOD. In contrast, the other site at UNB was not
      affected by macroalgal treatment, likely due to an initial community composed of
      a high proportion of subsurface-deposit feeders tolerant of stressful
      environments. Macroalgal abundances as low as 110-120 g dm/m2 had significant and
      rapid negative effects on macrobenthic invertebrates, providing a clear benchmark
      of adverse effects of macroalgal blooms on macrofaunal abundance and community
      structure, two indicators of ecosystem health. This information can inform the
      establishment of appropriate metrics for macroalgal abundance in eutrophic
      estuaries.

PMID- 24689143
TI  - Rigorous meta-analysis of life history correlations by simultaneously analyzing
      multiple population dynamics models.
AB  - Correlations among life history parameters have been discussed in the ecological
      literature for over 50 years, but are often estimated while treating model
      estimates of demographic rates such as natural mortality (M) or individual growth
      (k) as "data." This approach fails to propagate uncertainty appropriately because
      it ignores correlations in estimation errors between parameters within a species
      and differences in estimation error among species. An improved alternative is
      multi-species mixed-effects modeling, which we approximate using multivariate
      likelihood profiles in an approach that synthesizes information from several
      population dynamics models. Simulation modeling demonstrates that this approach
      has minimal bias, and that precision improves with increased number of species.
      As a case study, we demonstrate this approach by estimating M/k for 11 groundfish
      species off the U.S. West Coast using the data and functional forms on which pre
      existing, peer-reviewed, population dynamics models are based. M/k is estimated
      to be 1.26 for Pacific rockfishes (Sebastes spp.), with a coefficient of
      variation of 76% for M given k. This represents the first-ever estimate of
      correlations among life history parameters for marine fishes using several age
      structured population dynamics models, and it serves as a standard for future
      life history correlation studies. This approach can be modified to provide robust
      estimates of other life history parameters and correlations, and requires few
      changes to existing population dynamics models and software input files for both
      marine and terrestrial species. Specific results for Pacific rockfishes can be
      used as a Bayesian prior for estimating natural mortality in future fisheries
      management efforts. We therefore recommend that fish population dynamics models
      be compiled in a global database that can be used to simultaneously analyze
      observation-level data for many species in life history meta-analyses.

PMID- 24689144
TI  - Landscape genetics as a tool for conservation planning: predicting the effects of
      landscape change on gene flow.
AB  - For conservation managers, it is important to know whether landscape changes lead
      to increasing or decreasing gene flow. Although the discipline of landscape
      genetics assesses the influence of landscape elements on gene flow, no studies
      have yet used landscape-genetic models to predict gene flow resulting from
      landscape change. A species that has already been severely affected by landscape
      change is the large marsh grasshopper (Stethophyma grossum), which inhabits moist
      areas in fragmented agricultural landscapes in Switzerland. From transects drawn
      between all population pairs within maximum dispersal distance (< 3 km), we
      calculated several measures of landscape composition as well as some measures of
      habitat configuration. Additionally, a complete sampling of all populations in
      our study area allowed incorporating measures of population topology. These
      measures together with the landscape metrics formed the predictor variables in
      linear models with gene flow as response variable (F(ST) and mean pairwise
      assignment probability). With a modified leave-one-out cross-validation approach,
      we selected the model with the highest predictive accuracy. With this model, we
      predicted gene flow under several landscape-change scenarios, which simulated
      construction, rezoning or restoration projects, and the establishment of a new
      population. For some landscape-change scenarios, significant increase or decrease
      in gene flow was predicted, while for others little change was forecast.
      Furthermore, we found that the measures of population topology strongly increase
      model fit in landscape genetic analysis. This study demonstrates the use of
      predictive landscape-genetic models in conservation and landscape planning.

PMID- 24689145
TI  - Experimental canopy removal enhances diversity of vernal pond amphibians.
AB  - Vernal ponds are often treated as protected environments receiving special
      regulation and management. Within the landscapes where they are found, forest
      vegetation frequently dominates surrounding uplands and can grow to overtop and
      shade pond basins. Two bodies of research offer differing views of the role of
      forest canopy for vernal pond systems. Studies of landscape conversion suggest
      that removing forest overstory within uplands can cause local extinctions of
      amphibians by altering terrestrial habitat or hindering movement. Studies of
      canopy above pond basins imply an opposite relationship; encroachment of
      overstory vegetation can be associated with local extinctions potentially via
      changes in light, thermal, and food resource environments. Unresolved
      uncertainties about the role of forest canopy reveal significant gaps in our
      understanding of wetland species distributions and dynamics. Any misunderstanding
      of canopy influences is simultaneously important to managers because current
      practices emphasize promoting or conserving vegetation growth particularly within
      buffers immediately adjacent to ponds. We evaluated this apparent contradiction
      by conducting a landscape-scale, long-term experiment using 14 natural vernal
      ponds. Tree felling at six manipulated ponds was limited in spatial scope but was
      nevertheless effective in increasing water temperature. Compared with eight
      control ponds, manipulated ponds maintained more amphibian species during five
      years post-manipulation. There was little evidence that any species was
      negatively influenced, and the reproductive effort of species for which we
      estimated egg inputs maintained pretreatment population densities in manipulated
      compared with control ponds. Overall, our experiment shows that a carefully
      circumscribed reduction of overhead forest canopy can enhance the capacity of
      vernal ponds to support wildlife diversity and suggests a scale dependence of
      canopy influences on amphibians. These findings have implications for the
      connection between current wetland management practices and the goals of wetland
      stewardship and conservation of wetland-dependent species.

PMID- 24689146
TI  - Integrating population- and individual-level information in a movement model of
      Yellowstone bison.
AB  - Throughout the world, fragmentation of landscapes by human activities has
      constrained the opportunity for large herbivores to migrate. Conflict between
      people and wildlife results when migrating animals transmit disease to livestock,
      damage property, and threaten human safety. Mitigating this conflict requires
      understanding the forces that shape migration patterns. Bison Bos bison migrating
      from Yellowstone National Park into the state of Montana during winter and spring
      concern ranchers on lands surrounding the park because bison can transmit
      brucellosis (Brucella abortus) to cattle. Migrations have been constrained, with
      bison being lethally removed or moved back into the park. We developed a state
      space model to support decisions on bison management aimed at mitigating conflict
      with landowners outside the park. The model integrated recent GPS observations
      with 22 years (1990-2012) of aerial counts to forecast monthly distributions and
      identify factors driving migration. Wintering areas were located along decreasing
      elevation gradients, and bison accumulated in wintering areas prior to moving to
      areas progressively lower in elevation. Bison movements were affected by time
      since the onset of snowpack, snowpack magnitude, standing crop, and herd size.
      Migration pathways were increasingly used over time, suggesting that experience
      or learning influenced movements. To support adaptive management of Yellowstone
      bison, we forecast future movements to evaluate alternatives. Our approach of
      developing models capable of making explicit probabilistic forecasts of large
      herbivore movements and seasonal distributions is applicable to managing the
      migratory movements of large herbivores worldwide. These forecasts allow managers
      to develop and refine strategies in advance, and promote sound decision-making
      that reduces conflict as migratory animals come into contact with people.

PMID- 24689147
TI  - Spatial occupancy models applied to atlas data show Southern Ground Hornbills
      strongly depend on protected areas.
AB  - Determining the range of a species and exploring species--habitat associations
      are central questions in ecology and can be answered by analyzing presence-
      absence data. Often, both the sampling of sites and the desired area of inference
      involve neighboring sites; thus, positive spatial autocorrelation between these
      sites is expected. Using survey data for the Southern Ground Hornbill (Bucorvus
      leadbeateri) from the Southern African Bird Atlas Project, we compared advantages
      and disadvantages of three increasingly complex models for species occupancy: an
      occupancy model that accounted for nondetection but assumed all sites were
      independent, and two spatial occupancy models that accounted for both
      nondetection and spatial autocorrelation. We modeled the spatial autocorrelation
      with an intrinsic conditional autoregressive (ICAR) model and with a restricted
      spatial regression (RSR) model. Both spatial models can readily be applied to any
      other gridded, presence--absence data set using a newly introduced R package. The
      RSR model provided the best inference and was able to capture small-scale
      variation that the other models did not. It showed that ground hornbills are
      strongly dependent on protected areas in the north of their South African range,
      but less so further south. The ICAR models did not capture any spatial
      autocorrelation in the data, and they took an order, of magnitude longer than the
      RSR models to run. Thus, the RSR occupancy model appears to be an attractive
      choice for modeling occurrences at large spatial domains, while accounting for
      imperfect detection and spatial autocorrelation.

PMID- 24689148
TI  - Long-lived organisms provide an integrative footprint of agricultural land use.
AB  - Nitrogen (N) fertilizer runoff into rivers is linked to nutrient enrichment,
      hydrologic alteration, habitat degradation and loss, and declines in biotic
      integrity in streams. Nitrogen runoff from agriculture is expected to increase
      with population growth, so tracking these sources is vital to enhancing
      biomonitoring and management actions. Unionid mussels are large, long-lived,
      sedentary, primary consumers that transfer particulate material and nutrients
      from the water column to the sediments through their filter feeding. Because of
      these traits, mussels may provide a temporal integration of nitrogen inputs into
      watersheds. Our goals were to (1) establish a baseline delta15N signature for
      unionid mussels in watersheds not heavily influenced by agriculture for use in
      comparative analyses and (2) determine if mussels provide an integrative measure
      of N sources in watersheds with varying percentages of agriculture across large
      spatial scales. We compiled tissue delta15N data for 20 species of mussels from
      seven geographic areas, including 23 watersheds and 42 sample sites that spanned
      varying degrees of agricultural intensification across the eastern United States
      and Canada. We used GIS to determine land cover within the study basins, and we
      estimated net anthropogenic nitrogen inputs (NANI) entering these systems. We
      then determined the relationship between mussel tissue delta15N and percentage of
      land in agriculture (%AG) and net anthropogenic N loading. The delta15N of mussel
      tissue could be predicted from both %AG and net anthropogenic N loading, and one
      component of NANI, the amount of N fertilizer applied, was strongly related to
      the delta15N of mussel tissue. Based on our results, mussels occupying a system
      not affected by agricultural land use would have a baseline delta15N signature of
      approximately 2.0 pe thousand, whereas mussels in basins with heavy agriculture
      had delta15N signatures of 13.6 per thousand. Our results demonstrate that
      mussels integrate anthropogenic N input into rivers at a watershed scale and
      could be a good bioassessment tool for tracking agriculture N sources.

PMID- 24689149
TI  - Mapping habitat suitability for at-risk plant species and its implications for
      restoration and reintroduction.
AB  - The conservation of species at risk of extinction requires data to support
      decisions at landscape to regional scales. There is a need for information that
      can assist with locating suitable habitats in fragmented and degraded landscapes
      to aid the reintroduction of at-risk plant species. In addition, desiccation and
      water stress can be significant barriers to the success of at-risk plant
      reintroduction programs. We examine how airborne light detection and ranging
      (LiDAR) data can be used to model microtopographic features that reduce water
      stress and increase resource availability, providing information for landscape
      planning that can increase the success of reintroduction efforts for a dryland
      landscape in Hawaii. We developed a topographic habitat-suitability model (HSM)
      from LiDAR data that identifies topographic depressions that are protected from
      prevailing winds (high-suitability sites) and contrasts them with ridges and
      other exposed areas (low-suitability sites). We tested in the field whether high
      suitability sites had microclimatic conditions that indicated better-quality
      habitat compared to low-suitability sites, whether plant-response traits
      indicated better growing conditions in high-suitability sites, whether the
      locations of individuals of existing at-risk plant species corresponded with our
      habitat-suitability classes, and whether the survival of planted individuals of a
      common native species was greater in high-suitability, compared to low
      suitability, planting sites. Mean wind speed in a high-suitability field site was
      over five times lower than in a low-suitability site, and soil moisture and leaf
      wetness were greater, indicating less stress and greater resource availability in
      high-suitability areas. Plant height and leaf nutrient content were greater in
      high-suitability areas. Six at-risk species showed associations with high
      suitability areas. The survival of planted individuals was less variable among
      high-suitability plots. These results suggest that plant establishment and
      survival is associated with the habitat conditions identified by our model. The
      HSM can improve the survival of planted individuals, reduce the cost of
      restoration and reintroduction programs through targeted management activities in
      high-suitability areas, and expand the ability of managers to make landscape
      scale decisions regarding land-use, land acquisition, and species recovery.

PMID- 24689150
TI  - Variable wind, pack ice, and prey dispersion affect the long-term adequacy of
      protected areas for an Arctic sea duck.
AB  - With changing climate, delineation of protected areas for sensitive species must
      account for long-term variability and geographic shifts of key habitat elements.
      Projecting the future adequacy of protected areas requires knowing major factors
      that drive such changes, and how readily the animals adjust to altered resources.
      In the Arctic, the viability of habitats for marine birds and mammals often
      depends on sea ice to dissipate storm waves and provide platforms for resting.
      However, some wind conditions (including weak winds during extreme cold) can
      consolidate pack ice into cover so dense that air-breathing divers are excluded
      from the better feeding areas. Spectacled Eiders (Somateria fischeri) winter
      among leads (openings) in pack ice in areas where densities of their bivalve prey
      are quite high. During winter 2009, however, prevailing winds created a large
      region of continuous ice with inadequate leads to allow access to areas of dense
      preferred prey. Stable isotope and fatty acid biomarkers indicated that, under
      these conditions, the eiders did not diversify their diet to include abundant non
      bivalve taxa but did add a smaller, less preferred, bivalve species. Consistent
      with a computer model of eider energy balance, the body fat of adult eiders in
      2009 was 33-35% lower than on the same date (19 March) in 2001 when ice
      conditions allowed access to higher bivalve densities. Ice cover data suggest
      that the eiders were mostly excluded from areas of high bivalve density from
      January to March in about 30% of 14 winters from 1998 to 2011. Thus, even without
      change in total extent of ice, shifts in prevailing winds can alter the areal
      density of ice to reduce access to important habitats. Because changes in wind
      driven currents can also rearrange the dispersion of prey, the potential for
      altered wind patterns should be an important concern in projecting effects of
      climate change on the adequacy of marine protected areas for diving endotherms in
      the Arctic.

PMID- 24689151
TI  - Adaptive responses reveal contemporary and future ecotypes in a desert shrub.
AB  - Interacting threats to ecosystem function, including climate change, wildfire,
      and invasive species necessitate native plant restoration in desert ecosystems.
      However, native plant restoration efforts often remain unguided by ecological
      genetic information. Given that many ecosystems are in flux from climate change,
      restoration plans need to account for both contemporary and future climates when
      choosing seed sources. In this study we analyze vegetative responses, including
      mortality, growth, and carbon isotope ratios in two blackbrush (Coleogyne
      ramosissima) common gardens that included 26 populations from a range-wide
      collection. This shrub occupies ecotones between the warm and cold deserts of
      Mojave and Colorado Plateau ecoregions in western North America. The variation
      observed in the vegetative responses of blackbrush populations was principally
      explained by grouping populations by ecoregions and by regression with site
      specific climate variables. Aridity weighted by winter minimum temperatures best
      explained vegetative responses; Colorado Plateau sites were usually colder and
      drier than Mojave sites. The relationship between climate and vegetative response
      was mapped within the boundaries of the species-climate space projected for the
      contemporary climate and for the decade surrounding 2060. The mapped ecological
      genetic pattern showed that genetic variation could be classified into cool
      adapted and warm-adapted ecotypes, with populations often separated by steep
      dines. These transitions are predicted to occur in both the Mojave Desert and
      Colorado Plateau ecoregions. While under contemporary conditions the warm-adapted
      ecotype occupies the majority of climate space, climate projections predict that
      the cool-adapted ecotype could prevail as the dominant ecotype as the climate
      space of blackbrush expands into higher elevations and latitudes. This study
      provides the framework for delineating climate change-responsive seed transfer
      guidelines, which are needed to inform restoration and management planning. We
      propose four transfer zones in blackbrush that correspond to areas currently
      dominated by cool-adapted and warm-adapted ecotypes in each of the two
      ecoregions.

PMID- 24689152
TI  - Navigating nurse staffing: a new partnership in the new year.

PMID- 24689153
TI  - Resonant leadership and workplace empowerment: the value of positive
      organizational cultures in reducing workplace incivility.
AB  - Nursing leaders are indispensable in creating positive nursing work environments
      that retain an empowered and satisfied nursing workforce. Positive and supportive
      leadership styles can lower patient mortality and improve nurses' health, job
      satisfaction, organizational commitment, emotional exhaustion, and intent to stay
      in their position. The results of this study support the role of positive
      leadership approaches that empower nurses and discourage workplace incivility and
      burnout in nursing work environments. The findings also provide empirical support
      for the notion of resonant leadership, a relatively new theory of relationship
      focused leadership approaches. This research adds to the growing body of
      knowledge documenting the key role of positive leadership practices in creating
      healthy work environments that promote retention of nurses in a time of a severe
      nursing shortage.

PMID- 24689154
TI  - Gap analysis: synergies and opportunities for effective nursing leadership.
AB  - Gap analysis encompasses a comprehensive process to identify, understand,
      address, and bridge gaps in service delivery and nursing practice. onducting gap
      analysis provides structure to information gathering and the process of finding
      sustainable solutions to important deficiencies. Nursing leaders need to
      recognize, measure, monitor, and execute on feasible actionable solutions to help
      organizations make adjustments to address gaps between what is desired and the
      actual real-world conditions contributing to the quality chasm in health care.
      Gap analysis represents a functional and comprehensive tool to address
      organizational deficiencies. Using gap analysis proactively helps organizations
      map out and sustain corrective efforts to close the quality chasm. Gaining
      facility in gap analysis should help the nursing profession's contribution to
      narrowing the quality chasm.

PMID- 24689155
TI  - Nursing characteristics and patient outcomes.
AB  - To be effective at controlling costs while still providing safe, high-quality
      care, it is imperative to have the appropriate number of well-prepared, competent
      nurses. Health care systems need to evaluate the optimal characteristics of the
      nurse providing care that will promote quality patient outcomes while maintaining
      cost effectiveness. Results from this study showed an association between the
      unit with the lowest nursing intensity and the highest number of overall falls.
      Data from this study support the premise that added cost of increased staffing
      may actually prevent an adverse patient outcome and the financial cost of a
      noncovered expenditure. As institutional leaders evaluate the staffing patterns
      of nurses and the characteristics of nurses caring for patients, they must be
      aware of the financial impact of these factors.

PMID- 24689156
TI  - Nurse manager job satisfaction and intent to leave.
AB  - An electronic survey was used to collect data from 291 nurse managers working in
      U.S. hospitals. Seventy percent were satisfied or very satisfied with their jobs
      and 68% were either likely or very likely to recommend nursing management as a
      career choice. Seventy-two percent of these nurse managers were also planning to
      leave their positions in the next 5 years. The four most common reasons reported
      for intent to leave included burnout, career change, retirement, and promotion.
      Burnout was the most common reason cited by the entire sample but the fourth most
      common reason for leaving cited by those nurse managers who were planning to
      leave and also satisfied or very satisfied with their positions. Recommendations
      for nursing leaders include evaluating the workload of nurse managers, providing
      career counseling, and developing succession plans.

PMID- 24689157
TI  - We can do better.
AB  - We should not expect a new model or a brilliant new study to transform staffing
      in health care from hard to easy. Nurses can't change the complexity of our work;
      however, we can and must improve the art and science of staffing. e have not
      mastered the translation of evidence on staffing to influencing budgets,
      adjusting policies, procedures, and changing cultures as rapidly as we need.
      esearch has helped in countless ways, but we need more and there is still much to
      understand. ccurate data collection and a willingness to share that data with
      researchers will help advance the science of staffing. The road ahead is not easy
      and will take courage, tenacity, and a lot of energy.

PMID- 24689158
TI  - How will health reform affect demand for RNs?
AB  - The U.S. Bureau of Labor Statistics forecasts demand for registered nurses (RNs)
      will result in 3.5 million nursing jobs by 2020, marking a 26% increase over 10
      years. RN employment is expected to grow most rapidly in outpatient settings-
      particularly physician offices--and home health care. The Affordable Care Act
      will likely impact the places where RNs work, and the skills they need to be
      successful in these settings. RNs will be expected to serve as care coordinators,
      case managers, patient educators, and chronic care specialists. RNs with strong
      skills will be in high demand in the labor market.

PMID- 24689159
TI  - The financial impact of a clinical academic practice partnership.
AB  - New strategies to provide clinical experiences for nursing students have caused
      nursing schools and hospitals to evaluate program costs. A Microsoft Excel model,
      which captures costs and associated benefits, was developed and is described
      here. The financial analysis shows that the Clinical Academic Practice Program
      framework for nursing clinical education, often preferred by students, can offer
      financial advantages to participating hospitals and schools of nursing. The model
      is potentially a tool for schools of nursing to enlist hospitals and to help
      manage expenses of clinical education. Hospitals may also use the Hospital
      Nursing Unit Staffing and Expense Worksheet in planning staffing when students
      are assigned to units and the cost/benefit findings to enlist management support.

PMID- 24689160
TI  - Could this be the year to claim the corner office?
AB  - The health care industry is in the midst of chaos as we navigate through the
      uncertainty of reform, gridlock in Congress, and the largest change ever
      contemplated in the delivery of care as the epicenter moves to the community.
      Yet, history has repeatedly demonstrated that from chaos, opportunity is born.
      Creative nurse entrepreneurs, intrapreneurs, and innovative leaders have embraced
      this complexity and are beginning to reinvent their organizations and themselves
      to meet the challenge. Nurse leaders need to begin to shape the science around
      this level of sophisticated leadership, building our capacity as nurses and
      positioning others for inclusion into these unique ranks.

PMID- 24689161
TI  - Identifying which patients are at risk of suicide.

PMID- 24689163
TI  - Risk factor control is key in diabetic nephropathy.
AB  - Prolonged duration of diabetes, poor glycaemic control and hypertension are major
      risk factors for both diabetic nephropathy and cardiovascular disease. Optimising
      blood sugar control together with excellent control of blood pressure can reduce
      the risk of developing diabetic nephropathy. Diabetic nephropathy should be
      considered in any patient with diabetes when persistent albuminuria develops.
      Microalbuminuria is the earliest clinically detectable indicator of diabetic
      nephropathy risk. The majority of patients with diabetic nephropathy are
      appropriately diagnosed based on elevated urinary albumin excretion and/or
      reduced 0032-6518 renal function. Patients with type 2 diabetes should have
      annual urinary ACR measurements from the time of diabetes diagnosis while those
      with type 1 diabetes should commence five years after diagnosis. Blood pressure
      lowering to 130/80mmHg and reduction of proteinuria to <1 g/day retards
      progression of diabetic nephropathy and reduces the number of cardiovascular
      events. Drugs that block the renin-angiotensin-aldosterone system (RAAS) are
      effective in reducing proteinuria, managing hypertension and reducing
      cardiovascular risk. Unless there are clear contraindications or intolerance all
      patients with diabetic nephropathy should be prescribed an ACEI or ARB. Stopping
      an ACEI or ARB during intercurrent illness or times of volume depletion is
      critically important. Patients with diabetic nephropathy should have at least
      yearly measurements of blood pressure, renal function and urinary ACR.

PMID- 24689164
TI  - Renal replacement therapy should be tailored to the patient.
AB  - End-stage renal disease (ESRD) describes loss of kidney function which is both
      substantial and irreversible. It is associated with acute life-threatening
      complications such as hyperkalaemia and pulmonary oedema, and chronic metabolic
      derangements that cannot be sustained in the long-term. Patient education is
      paramount in ESRD management. The form of renal replacement therapy (RRT)
      instituted should primarily be based on patient preference subsequent to an
      individually tailored education programme from specialist staff. This programme
      needs to take into account the patient's comorbidities and any contraindications
      to specific modalities of RRT. Transplantation replicates normal renal physiology
      much more closely than either dialysis modality. Assessment for transplantation
      requires consideration of the patient's suitability for general anaesthetic and
      surgery. Patients need to have an adequate blood supply and urinary drainage, and
      space for a kidney. They must also be suitable candidates for long-term
      immunosuppression. Ideally patients with ESRD should have a pre-emptive
      transplant before they require dialysis. Ninety per cent of recipients of a live
      donor transplant in the UK in 1999-2001 were alive ten years later, compared with
      74% of deceased donor recipients. There is no conclusive evidence that either
      dialysis modality is superior, and unless there are obvious reasons why one
      therapy is unsuitable, patient preference is usually the deciding factor.
      Peritoneal dialysis (PD) does not provide the same level of fluid and toxin
      removal as haemodialysis (HD) and many patients will be forced to transfer to HD
      within two to three years as PD gradually loses effectiveness. For those who will
      be suitable for transplantation, optimum management of diabetes, smoking
      cessation, weight loss, and general fitness is crucial in facilitating this.

PMID- 24689165
TI  - Improving the management of seborrhoeic dermatitis.
AB  - Seborrhoeic dermatitis usually starts at puberty with a peak incidence at 40
      years of age and is more common in males. Patients develop symmetrical, well
      demarcated, dull or yellowish red patches and plaques with overlying adherent,
      yellowish greasy scales. Seborrhoeic dermatitis has a distinctive distribution in
      areas rich in sebaceous glands - the scalp, eyebrows, glabella, nasolabial and
      nasofacial folds, cheeks, peri-auricular skin, pre-sternal and interscapular
      areas. It may occur in flexures, especially the axillae, groin, anogenital skin,
      infra-mammary skin and the umbilicus. Some patients may develop blepharitis with
      erythematous eyelids and destruction of eyelash follicles. Patients with HIV
      infection, neurological diseases, including parkinsonism and cranial nerve
      palsies, have a higher incidence of seborrhoeic dermatitis. Patients presenting
      with sudden onset severe seborrhoeic dermatitis should be screened for risk
      factors for HIV. Patients should be referred in the following situations:
      diagnostic uncertainty - consider other differential diagnoses; failure to
      respond to first-line treatment after four weeks - consider secondary changes
      e.g. bacterial infection, flexural intertrigo, lichenification, otitis externa;
      and severe/widespread disease. Patients with seborrhoeic dermatitis have a good
      prognosis, particularly infantile seborrhoeic dermatitis, which usually remits
      within a few weeks or months and does not recur.

PMID- 24689166
TI  - Eye problems.

PMID- 24689167
TI  - Nephroptosis and mental disorders. 1914.

PMID- 24689168
TI  - Why we must be honest with our patients.

PMID- 24689169
TI  - History of regulatory requirements for poultry biologics in the United States,
      1970s to 1990s.
AB  - By the end of the 1960s, The United States Department of Agriculture (USDA) had
      established the basic purity and safety standards for poultry biologics in the
      United States and had licensed products to address many of the major poultry
      diseases of concern at that time. The emergence of new diseases, advances in
      scientific technology, and changes in poultry husbandry practices that occurred
      in the 1970s to the 1990s required the development of many new and amended
      regulatory requirements to keep abreast of the changing needs of the poultry
      industry. Veterinary Services often approved the use of special or conditional
      licensing procedures to shorten the time to license products needed to address
      emerging diseases. Infectious bronchitis, bursal disease, fowl cholera, duck
      virus enteritis, avian influenza, and other vaccines were rapidly licensed to
      address emerging disease problems using this procedure. Changes in labeling and
      packaging requirements were made to address changing vaccination practices.
      Veterinary Services permitted diluents to be shipped separate from product, first
      for Marek's disease vaccine and later for vaccines recommended for administration
      by automatic vaccinating machines. The maximum number of doses permitted to be in
      one container and package were also amended to address the increased size of
      poultry flocks. Veterinary Services also approved the use of split manufacturing
      procedures that permitted two or more licensed manufacturers to work together in
      the production of a product. This innovative use of licensing products for
      further manufacture allowed the industry to use production facilities more
      efficiently and provided a wider variety of combination products. In 1985,
      Congress passed an amendment to the Virus-Serum-Toxin Act that gave USDA the
      authority to regulate all veterinary biological products shipped in or from the
      United States. This amendment brought intrastate biologics manufacturers under
      federal jurisdiction and ensured all biological products shipped in or from the
      United States met the same standards of purity, safety, potency, and efficacy.
      The development of new recombinant DNA (r-DNA) techniques for the production of
      vaccines required USDA to establish new procedures and rules for the review of
      these products prior to their release into the environment and eventual
      licensure. Compliance with the National Environmental Policy Act required the
      preparation of environmental risk assessments and public participation in the
      field testing and licensing of live r-DNA products. This article addresses some
      of the history of these and other changes in regulatory requirements for poultry
      products that took place in the 1970s to the 1990s, but space does not permit us
      to address all of the changes that have occurred. We have presented some of what
      we consider the most notable events in this process and leave it up to future
      historians to address events that may not have been included.

PMID- 24689170
TI  - Gene detection, virus isolation, and sequence analysis of avian leukosis viruses
      in Taiwan country chickens.
AB  - Avian leukosis virus (ALV) infection in Taiwan Country chickens (TCCs) was
      investigated by using gene detection, virus isolation, and sequence analysis. The
      blood samples of 61 TCC flocks at market ages from a slaughter house were
      screened for exogenous ALVs using polymerase chain reaction to investigate the
      ALV infection status. The buffy coats from three breeder and four commercial
      chicken flocks were cocultured with DF-1 cells to isolate the virus. The full
      proviral DNA genomes of two ALV isolates were sequenced, analyzed, and compared
      with reference ALV strains. The gene detection results showed that 60 and 43 of
      the 61 flocks were infected with subgroup A of ALV (ALV-A) and subgroup J of ALV
      (ALV-J), respectively. Virus isolation results showed that five ALV-As and two
      ALV-Js were isolated from those seven TCC flocks. The full sequences of the
      isolates showed that isolate TW-3577 possessed a myeloblastosis-associated virus
      1 gp85 coding region and an ALV-J 3'-untranslated region (3'UTR) and was similar
      to ordinary ALV-A. However, TW-3593 was unique. The 3'UTR of this isolate
      displayed high identity to endogenous counterpart sequence and its gp85 was
      different from all subgroups. This unique ALV is common in Taiwan.

PMID- 24689171
TI  - Identification and in vitro characterization of a Marek's disease virus-encoded
      Ribonucleotide reductase.
AB  - Marek's disease virus (MDV) encodes a ribonucleotide reductase (RR), a key
      regulatory enzyme in the DNA synthesis pathway. The gene coding for the RR of MDV
      is located in the unique long (UL) region of the genome. The large subunit is
      encoded by UL39 (RR1) and is predicted to comprise 860 amino acids whereas the
      small subunit encoded by UL40 (RR2) is predicted to be 343 amino acids long.
      Immunoprecipitation analysis of MDV-1 (GA strain)-infected cells with T81, a
      monoclonal antibody specific for RR of MDV, identified two major proteins of
      90,000 and 40,000 daltons, corresponding to RR1 and RR2, respectively. In
      addition, RR was abundantly expressed in the cytoplasm of cells infected with 51
      strains of MDV belonging to MDV serotypes 1, 2, and 3 as demonstrated by
      immunofluorescence staining. Northern blot analysis of RNA extracted from MDV
      infected cells showed a major band of around 4.4 kb in size corresponding to the
      RR1 and RR2 transcripts. In vivo, RR was abundantly expressed in lymphoid organs
      and feather follicle epithelium of MDV-infected chickens during early cytolytic
      infection, as determined by immunohistochemistry. There was, however, no
      expression of RR in MDV-induced tumors in lymphoid organs. The abundant
      expression of RR in MDV-infected chicken may suggest an important role of RR in
      the conversion of ribonucleotides to deoxyribonucleotides for MDV DNA synthesis.

PMID- 24689172
TI  - Safety evaluation of lasalocid use in Chinese ring-necked pheasants (Phasianus
      colchicus).
AB  - Coccidiosis remains a significant threat to the welfare of game farm-reared
      pheasants in the United States. Although lasalocid has been demonstrated to be
      effective against pheasant specific coccidia, information regarding its safety in
      this species is lacking. The purpose of this study was to gather data on the
      safety of lasalocid when fed to Chinese ring-necked pheasants at one, two, and
      three times the recommended high dose of lasalocid used for prevention of
      coccidiosis in other poultry at three times the normal treatment period. Pheasant
      chicks (approximately 1 day-old; n = 160) were randomly blocked by sex into four
      treatment groups and given their respective diets continuously for 6 wk. No
      significant differences were observed in overall feed consumption, weight gain,
      feed conversion rates, clinical pathology measurements, or tissue gross and
      histopathologic evaluations between controls and treatment groups associated with
      lasalocid administration. Based on the results of this study it appears that
      lasalocid fed at the recommended rate of 125 ppm is safe in Chinese ring-necked
      pheasants.

PMID- 24689173
TI  - Safety and efficacy of a turkey herpesvirus vector laryngotracheitis vaccine for
      chickens.
AB  - Turkey herpesvirus vector laryngotracheitis vaccine (HVT/LT) expressing the
      glycoprotein B gene of laryngotracheitis virus (LTV) has been developed. In vitro
      growth kinetics of HVT/LT were similar to those of parental turkey herpesvirus
      (HVT), FC-126 strain. Genetic and phenotypic stabilities of HVT/LT after in vitro
      (in cell culture) or in vivo (in chickens) passage were confirmed by various
      assays, including Southern blot analysis, western blot analysis, and an indirect
      immunofluorescence assay. Safety of HVT/LT was assessed by an overdose study as
      well as by a backpassage study in specific-pathogen-free (SPF) chickens. The
      overdose study indicated that HVT/LT did not cause any adverse effects in
      chickens. The backpassage study confirmed that HVT/LT does not revert to
      virulence after five passages in chickens. The vaccine did not transmit laterally
      from vaccinated chickens to commingled nonvaccinated chickens. Efficacy of HVT/LT
      was evaluated in SPF layer chickens after vaccination by the subcutaneous route
      at 1 day of age. The majority of the vaccinated chickens (92%-100%) were
      protected against challenge with virulent LTV at 7 wk of age. Efficacy of HVT/LT
      was further evaluated in broiler chickens from a commercial source after in ovo
      vaccination to embryos at 18 days of incubation. After challenge with virulent
      LTV at 21 and 35 days of age, 67% and 87% of HVT/LT-vaccinated chickens did not
      develop LT clinical signs, respectively, while 100% (21 days of age) and 73% (35
      days of age) of the challenge control chickens showed clinical signs of LT. These
      results suggest that HVT/LT is a safe and efficacious vaccine for control of
      laryngotracheitis (LT).

PMID- 24689174
TI  - The use of dual-energy X-ray absorptiometry to assess the impact of Eimeria
      infections in broiler chicks.
AB  - A number of parameters have been used to assess the impact ofcoccidiosis on
      chickens in clinical settings as well as in experimental studies. However, a
      rapid way to determine body composition would be useful to evaluate or compare
      responses to coccidia and could give further insight into the metabolic impact of
      infection. The current study evaluates the use of dual X-ray absorptiometry
      (DEXA) to determine the impact of coccidiosis on body composition in chicks
      receiving inoculations with single or mixed species of Eimeria. Chicks infected
      with Eimeria maxima, Eimeria acervulina, or Eimeria tenella had altered
      parameters of body composition as measured by DEXA at 6 days postinfection (PI).
      The greatest effects were noted in birds infected with E. acervulina or E.
      maxima, where lean mass and fat were reduced from control values about 75% and
      85%, respectively. In chicks infected with E. tenella, tissue and fat were
      reduced about 10%. Bone mineral content (BMC) was about 75% of control values in
      birds infected with E. acervulina or E. maxima, but only E. acervulina altered
      bone mineral density (BMD). The decreases in BMC and BMD are likely due to
      malabsorption. In chicks receiving a mixed coccidian infection, all DEXA
      parameters were significantly decreased at 8 days PI compared with age-matched
      controls. As with single infections, BMD and BMC were significantly depressed (P
      < 0.05). Values of all DEXA parameters were near 92% of control values by day 16
      PI. Analysis of all birds in the current study indicates DEXA tissue weight
      slightly underestimated the gravimetrically measured weight by about 3%. The
      current results demonstrate that DEXA is a potentially important tool for the
      rapid evaluation of the effect of coccidiosis on broiler chicks and suggest it
      can be useful for evaluation of vaccines and other disease controls.

PMID- 24689175
TI  - Pathogenesis in Eurasian tree sparrows inoculated with H5N1 highly pathogenic
      avian influenza virus and experimental virus transmission from tree sparrows to
      chickens.
AB  - Small wild birds that routinely enter poultry farms may be possible vectors of
      Asian lineage H5N1 highly pathogenic avian influenza virus. In this study, we
      conducted experimental infections using wild-caught Eurasian tree sparrows
      (Passer montanus) to evaluate their possible epidemiological involvement in virus
      transmission. When tree sparrows were intranasally inoculated with the virus at a
      low or high dose, all sparrows excluding euthanatized birds died within 11 days
      after inoculation. Viruses were frequently isolated from the drinking water, oral
      swabs, and visceral organs of the sparrows. Immunohistochemical analysis revealed
      that the virus replicated strongly in the central nervous system, heart, and
      adrenal gland following primary infection in the upper respiratory tract and a
      probable subsequent viremic stage. In the contact infection study using virus
      inoculated sparrows and untreated contact chickens, more than half of all
      chickens died from viral infection. In the virus transmission study in which
      chickens were given drinking water collected from virus-inoculated sparrows,
      mortality due to viral infection was observed in chickens. Our data suggest that
      Eurasian tree sparrows could be biological vectors of the H5N1 highly pathogenic
      avian influenza virus. In addition to frequent virus detection in the drinking
      water of sparrows, the results of the virus transmission study suggest that
      waterborne pathways could be important for viral transmission from tree sparrows
      to poultry.

PMID- 24689176
TI  - Vaccination of turkeys with Clostridium septicum bacterin-toxoid: evaluation of
      protection against clostridial dermatitis.
AB  - Clostridial dermatitis is an acute disease causing high mortality in turkeys.
      Both Clostridium septicum and Clostridium pefringens have been isolated from
      these cases; however, reports from several diagnostic laboratories indicate an
      increased isolation rate of C septicum compared with C. perfringens from cases of
      clostridial dermatitis in recent years. Previous studies suggested C. septicum
      was more potent than C. perfringens in causing clostridial dermatitis in turkeys.
      The objective of this study was to develop and evaluate the use of a C. septicum
      bacterin-toxoid to control clostridial dermatitis in turkeys. A C. septicum
      bacterin-toxoid was prepared and was initially tested in 6-wk-old commercial
      turkeys under laboratory conditions for its safety and efficacy. Subsequently,
      the bacterin-toxoid was evaluated for use in commercial turkey farms with a
      consistent history of clostridial dermatitis. Birds in the field were vaccinated
      subcutaneously once at 6 wk of age with C. septicum bacterin-toxoid, and then
      mortality in both vaccinated and unvaccinated groups was recorded and compared.
      Blood samples from birds in both groups were examined using ELISA to detect
      antibody response to the C. septicum toxoid. The C. septicum bacterin-toxoid was
      found to be safe and to elicit antibodies against the toxoid. In vaccinated
      commercial turkeys, control of clostridial dermatitis was achieved via antibiotic
      use and clostridial dermatitis mortality was significantly reduced compared with
      that of birds in the unvaccinated group. The C. septicum bacterin-toxoid seems to
      be a valuable tool for the turkey industry to reduce losses due to clostridial
      dermatitis.

PMID- 24689177
TI  - Rapid detection of Mycoplasma synoviae and avian reovirus in clinical samples of
      poultry using multiplex PCR.
AB  - Mycoplasma synoviae and avian reovirus (ARV) are associated with several disease
      syndromes in poultry and cause notable global economic losses in the poultry
      industry. Rapid and efficient diagnostics for these avian pathogens are important
      not only for disease control but also for prevention of clinical disease
      progression. However, current diagnostic methods used for surveillance of these
      diseases in poultry flocks are laborious and time-consuming, and they have low
      sensitivity. The multiplex PCR (mPCR) developed in this study has been proven to
      be both sensitive and specific for simultaneous M. synoviae and ARV detection and
      identification in clinical samples. To evaluate the mPCR assay, the diagnostic
      test was applied to different clinical samples from natural and experimental M.
      synoviae and ARV-infected poultry. Results were compared with serologic, single
      PCR, and immunofluorescence analyses. Tibiotarsal articulation could be the best
      target for simultaneous detection of M. synoviae and ARV infection. The detection
      limit by visualization of mPCR-amplified products was 100 pg for both pathogens.
      Overall, the mPCR developed and standardized in this research is a useful tool
      for diagnosis and screening and for surveillance and control of M. synoviae and
      ARV infection in poultry flocks.

PMID- 24689178
TI  - Emergence of a new genotype of avian infectious bronchitis virus in Brazil.
AB  - Infectious bronchitis virus (IBV) is the agent of a highly contagious disease
      that affects domestic fowl (Gallus gallus). Recent reports showed a high
      prevalence of one main IBV genotype (Brazil or BR-I) with low genetic diversity
      in commercial poultry flocks from Brazil. This research analyzed IBV positive
      poultry flocks from different rearing regions to verify the S1 gene variability
      and geographic distribution of variant IBV strains in recent years (2010 and
      2011). Samples of IBV-positive flocks were obtained from 60 different farms.
      Forty-nine partial S1 gene sequences were determined and aligned for phylogenetic
      and amino acid similarity analyses. Eleven samples (22.4%) were similar to
      Massachusetts vaccine strains (Mass genotype) and 34 samples (69.4%) to the
      previously characterized Brazilian BR-I genotype. Interestingly, the remaining
      four samples (8.2%) clustered into a new IBV variant genotype (Brazil-II or BR
      II), divergent from the BR-I. A unique nucleotide sequence insertion coding for
      five amino acid residues was observed in all the Brazilian variant viruses (BR-I
      and BR-II genotypes). These results show a higher genetic diversity in Brazilian
      IBV variants than previously described.

PMID- 24689179
TI  - Evaluation of Maryland backyard flocks and biosecurity practices.
AB  - Domesticated poultry are susceptible to infectious and zoonotic diseases and can
      serve as a transmission source to other bird and human populations. In recent
      years, the number of noncommercial poultry has been on the rise in the United
      States. To evaluate potential risks of this growing population, a descriptive
      epidemiologic survey was conducted among Maryland backyard flocks. Owner and
      flock demographics were characterized as well as management practices such as
      husbandry, human-to-bird interaction, bird exposure risks, poultry health status,
      and biosecurity. Data from the 41 returned questionnaires indicated a median
      flock size of 38 birds (range, 3-901). Chickens accounted for 86.5% of the
      reported birds overall. Just over half of the owners (51.2%) kept chickens only,
      with the remaining backyard flocks consisting of chickens, other gallinaceous
      species, waterfowl, or a combination. Of flocks with multiple species, 70.0% of
      owners did not keep them separate. Almost two thirds of owners (61.0%) had kept
      poultry for < or = 5 yr, with 44.0% of all flocks on free range. Over the past 2
      yr, predation was the highest cause of specific mortality (57.1%) followed by
      disease (30.2%), unknown (8.7%), and injury (4.0%), and over half of owners
      (56.1%) reported signs of disease in their flock within the last 6 mo.
      Biosecurity practices were highly variable among flocks. Data from this study
      identified gaps in the disease prevention and biosecurity practices of backyard
      flocks. These results can be useful in developing educational extension and
      outreach programs as well as policies, in efforts to further mitigate the spread
      of diseases.

PMID- 24689180
TI  - Campylobacter infection has different outcomes in fast- and slow-growing broiler
      chickens.
AB  - Campylobacter spp. are frequently carried by poultry, but they are not believed
      to cause significant disease in these animals. Modern poultry breeds have been
      selected to grow rapidly under intensive conditions, but recently, consumers have
      moved toward purchasing birds produced in higher welfare, free-range or organic
      systems. Birds reared in these systems tend to be a slower growing breed and are
      fed a different diet. Birds reared in such systems are stocked at a lower density
      compared with the standard conventional broilers, and they have access to
      environmental enrichment, such as perches. In previous research, these slower
      growing birds have been shown to have different levels of Campylobacter carriage
      in commercial rearing conditions, but the reasons for, and effect of, these
      different levels are unknown; is it the bird breed, diet, or environmental
      conditions? In this study, experimental flocks of fast- and slow-growing breeds
      of broiler chickens were reared to a standard commercial slaughter weight, with
      their weight gain being measured during the growing period. At 21 days, birds
      were either infected with Campylobacter jejuni or given a placebo as control.
      Cohorts of birds were euthanatized at various intervals, and samples were taken
      for examination for Campylobacter. The fast-growing birds gained weight more
      rapidly than the slow-growing birds. By 2 days postinfection (dpi), C. jejuni was
      detected in the caeca and by enrichment from the liver and spleen samples from
      both breeds of birds. Low-level colonization persisted in the spleen and liver
      samples but was undetectable by 28 dpi. Fast- and slow-growing birds did not show
      detectably different levels of Campylobacter carriage. Infection with C. jejuni
      affected the incidence of hock marks and pododermatitis in both breeds of birds,
      but the differences were greater with the fast-growing breed compared with the
      uninfected control birds. In addition, the incidence of pododermatitis was
      significantly higher in Campylobacter-positive fast-growing birds than in their
      slower-growing counterparts. The results show that infection with Campylobacter
      can have an indirect welfare effect on birds via increased incidence of hock
      marks and pododermatitis.

PMID- 24689181
TI  - Pathogenicity of low and highly virulent Chlamydia psittaci isolates for specific
      pathogen-free chickens.
AB  - In commercially raised poultry, chlamydiosis mostly seems to occur on turkey or
      duck farms, sometimes associated with zoonotic transmission and disease
      (psittacosis) in humans. However, Chlamydia infections are apparently emerging in
      chickens, and information on the virulence of Chlamydia in chickens is limited.
      Up-to-date Chlamydia psittaci genotypes B and D are most frequently found in
      broilers. We examined the pathogenicity of the well-characterized C. psittaci
      genotype B (CP3) and D (92/1293) strains in experimentally (aerosol) infected
      specific-pathogen-free chickens. Both strains caused conjunctivitis, rhinitis,
      and dyspnea. Pharyngeal and cloacal C. psittaci excretion was observed in all
      infected animals, indicative for systemic dissemination as proven by
      immunofluorescence staining of frozen tissue sections. Histopathologic lesions
      were present in all infected chickens. However, differences in pathology were
      observed. Genotype D led to mortality and more severe clinical signs and lesions
      as compared to genotype B, which showed lower virulence.

PMID- 24689182
TI  - Evaluation of infectious bronchitis virus Arkansas-type vaccine failure in
      commercial broilers.
AB  - Infectious bronchitis virus (IBV) causes an upper respiratory tract disease in
      chickens and is highly contagious. Many different types of the virus exist, but
      only a few types are used as attenuated live vaccines in the commercial poultry
      industry. Of the vaccine types used, the Arkansas (Ark)-type virus is most
      frequently reisolated from vaccinated broilers. Previous research has suggested
      that incomplete clearance of Ark-type vaccine virus plays a role in the
      inadequate protection observed when vaccinated broilers are challenged with
      pathogenic Ark virus. In this study, we examine routes of vaccine administration
      using multiple IBV types including Ark in an effort to understand why Ark
      vaccines do not provide good protection and persist in commercial broilers. We
      found that interference between different types of IBV vaccines was not occurring
      when combined and administered using a commercial hatchery spray cabinet. Also,
      Ark vaccine virus was not efficacious in 1-day-old broilers when sprayed using a
      hatchery spray cabinet, but it gave good protection when administrated by eyedrop
      inoculation. We also found that the amount of Ark vaccine virus was low or
      undetectable in choanal swabs out to 35 days postvaccination when vaccine was
      administered by eyedrop or drinking water. Alternatively, a subpopulation of the
      Ark vaccine isolated from a vaccinated bird, Ark-RI-EP1, showed a peak titer at 7
      10 days of age when given by the same routes, suggesting that the Ark-RI-EP1 was
      more fit with regard to infection, replication in the birds, or both. Moreover,
      we found that detection of IBV vaccine virus early after administration,
      regardless of strain or route, correlated with protection against homologous
      challenge and may thus be a good indicator of vaccine efficacy in the field
      because humoral antibody titers are typically low or undetectable after
      vaccination. These experiments provided key findings that can be used to direct
      efforts for improving the efficacy of IBV Ark-type vaccines given in the
      hatchery. They also elucidated factors contributing to the persistence of Ark
      vaccine in the field.

PMID- 24689183
TI  - Inhibition of Newcastle disease virus replication by lentivirus-mediated RNA
      interference.
AB  - Small interfering RNA (siRNA)-induced RNA degradation can specifically inhibit
      viral infection and has been extensively investigated for its efficacy as an
      antiviral therapeutic approach. In this study we constructed a lentivirus vector
      carrying a U6-short hairpin RNA expression cassette to express siRNAs in vero
      cells. The lentivirus vector also expressed an enhanced green fluorescence
      protein as a reporter. Stable siRNA-expressing cell lines were successfully
      established, and the inhibition efficiencies of rationally designed siRNAs
      targeting conserved genomic regions of the Newcastle disease virus, an important
      disease of poultry world wide, were assessed. Our results showed that siRNAs
      targeting the nucleoprotein and matrix gene potently inhibited viral replication.
      Our study indicates that lentivirus-mediated delivery of siRNA and the resulting
      gene silencing can be used to study the functions of genes in viral replication
      and may have a potential transgenic antiviral application in poultry.

PMID- 24689184
TI  - Experimental assessment of houseflies as vectors in avian influenza subtype H5N1
      transmission in chickens.
AB  - In this study, laboratory-reared houseflies were experimentally exposed to the
      high pathogenicity avian influenza virus (HPAI) subtype H5N1 virus to evaluate
      the houseflies as vectors in HPAI-H5N1 virus transmission in chickens. One
      hundred and fifty houseflies (Musca domestica L.) were equally allocated into
      three groups. Groups 2 and 3 were exposed to the HPAI-H5N1 virus by allowing the
      flies to consume food containing the virus for 15 min, while the flies in group 1
      were allowed to consume H5N1-free food and would serve as a negative control
      group. Group 2 flies were euthanatized immediately after H5N1 exposure, while
      group 3 were held at room temperature for 24 hr and euthanatized. The houseflies
      in the transmission of the HPAI-H5N1 virus were examined by challenging three
      groups of housefly homogenates into layer chickens via the oral drop. Morbidity
      and mortality were observed for 14 days, and virus shedding monitored via
      oropharyngeal swabs (OS) and cloacal swabs (CS), which were collected daily and
      determined by real-time reverse transcription-PCR and virus titration.
      Experimental challenge showed that all the chickens of groups 2 and 3 died within
      7 days of inoculation. The OS had higher concentrations of virus than CS.
      Moreover, the chickens of group 2 had higher concentrations of virus shedding
      than the chickens of group 3. Immunohistochemistry detected the nucleoprotein of
      the type A influenza virus in all tissue samples collected, including the
      trachea, duodenum, pancreas, and brain. In summary, this study demonstrates that
      houseflies could serve as vectors in HPAI-H5N1 virus transmission in chickens
      under experimental conditions.

PMID- 24689185
TI  - Efficacy of a live attenuated Escherichia coli O78:K80 vaccine in chickens and
      turkeys.
AB  - A candidate live vaccine for avian pathogenic Escherichia coli (APEC) was
      constructed from a virulent field APEC 078 strain by mutation of the aroA gene.
      The mutant was highly similar to the parent wild-type strain in respect of colony
      morphology, motility, growth in suspension, hemagglutination, Congo Red binding,
      HEp-2 cell adhesion, and the elaboration of surface antigens type 1 fimbriae and
      flagella, although production of curli fimbriae was reduced marginally. The
      mutant proved avirulent when inoculated into 1-day-old chicks by spray
      application and when presented again in the drinking water at 7 days of age.
      Chickens and turkeys vaccinated with an 078 aroA mutant were protected against a
      challenge at 6 wk of age by virulent APEC strains.

PMID- 24689186
TI  - Effects of aflatoxins on performance and exocrine pancreas of broiler chickens.
AB  - The aim of this research was to evaluate, on a weekly basis, the effects of
      aflatoxins on the activity of digestive enzymes (alpha-amylase, lipase, and
      trypsin) in the pancreas as well as on the performance and histology of pancreas
      in broiler chickens over the course of 42 days. One thousand and eighty 1-day-old
      male Cobb broilers were divided into four treatments with 18 replicates and 15
      birds per replicate (i.e., 270 broilers per treatment). Treatments were
      established according to the amount of aflatoxins added to the diet, as follows:
      T1 = 0 mg of aflatoxins per kilogram of feed (mg/kg); T2 = 0.7 mg/kg; T3 = 1.7
      mg/kg; and T4 = 2.8 mg/kg. Pancreas sample collection was performed from one bird
      out of each replicate at 7, 14, 21, 28, 35, and 42 days of experiment, which
      yielded a total of 18 samples per treatment on each collection. Each sample was
      homogenized in distilled water, frozen in liquid nitrogen, lyophilized, and
      stored at -20 C until analysis. Performance parameters (body weight, feed
      consumption, and feed conversion rate) were measured at 21, 35, and 42 days of
      experiment. At the end of the experiment (42 days), six birds from each treatment
      were randomly chosen for histologic evaluation of the pancreas. The presence of
      aflatoxins in the diet induced a negative effect on all performance parameters.
      The pancreatic activity of lipase and alpha-amylase were significantly increased
      in treatments T3 and T4, while the specific activity of trypsin was only affected
      during treatment T4. In addition, several histologic changes were observed in the
      pancreas of birds receiving aflatoxin-contaminated feed. Aflatoxins present in
      the feed determined an increase in the activity of pancreatic enzymes in
      broilers, affecting the digestibility of the diet, thereby leading to losses in
      performance and productivity.

PMID- 24689187
TI  - Enhanced innate immune responses in a brood parasitic cowbird species:
      Degranulation and oxidative burst.
AB  - We examined the relative effectiveness of two innate immune responses in two
      species of New World blackbirds (Passeriformes, Icteridae) that differ in
      resistance to West Nile virus (WNV). We measured degranulation and oxidative
      burst, two fundamental components of phagocytosis, and we predicted that the
      functional effectiveness of these innate immune responses would correspond to the
      species' relative resistance to WNV. The brown-headed cowbird (Molothrus ater),
      an obligate brood parasite, had previously shown greater resistance to infection
      with WNV, lower viremia and faster recovery when infected, and lower subsequent
      antibody titers than the red-winged blackbird (Agelaius phoeniceus), a close
      relative that is not a brood parasite. We found that cowbird leukocytes were
      significantly more functionally efficient than those of the blackbird leukocytes
      and 50% more effective at killing the challenge bacteria. These results suggest
      that further examination of innate immunity in the cowbird may provide insight
      into adaptations that underlie its greater resistance to WNV. These results
      support an eco-immunological interpretation that species like the cowbird, which
      inhabit ecological niches with heightened exposure to parasites, experience
      evolutionary selection for more effective immune responses.

PMID- 24689188
TI  - Species determination of fowl adenoviruses based on the 52K gene region.
AB  - In the present study, the classification of fowl adenoviruses (FAdVs) based on a
      part of the 52K gene region was described. A total of 44 FAdV field samples from
      different countries and sources were detected using a recently developed SYBR
      Green-based real-time PCR. Amplified products were sequenced, and phylogenetic
      analyses were conducted on the basis of the 116-bp region. For comparison, the
      already published sequences of the 52K gene region of aviadenoviruses were used
      in the analyses. The phylogenetic analysis allowed the grouping of the FAdVs into
      the established five different FAdV species: Fowl adenovirus A to Fowl adenovirus
      E. The existence of the species was supported by high bootstrap values (> 70%).
      This method provides the advantages of quantitation and high sensitivity for FAdV
      detection in combination with species assignment.

PMID- 24689189
TI  - An Avian coronavirus in quail with respiratory and reproductive signs.
AB  - An Avian coronavirus was detected in pools of lungs, tracheas, female
      reproductive tracts, kidneys, and enteric contents from quail (Coturnix coturnix
      japonica) and laying hen flocks, with and without infectious bronchitis (IB)-like
      signs, cohoused in farms located in two states of southeastern Brazil during 2009
      2010. Although Avian metapneumovirus subtype B was found in two layers samples,
      Newcastle disease virus was not found in quail or in hens. Based on DNA sequences
      for the 3'-untranslated region and the gene encoding the RNA-dependent RNA
      polymerase, this avian coronaviruses in quail is an IB virus-like
      gammacoronavirus.

PMID- 24689190
TI  - Development and application of quantitative real-time PCR for the rapid detection
      of hemorrhagic enteritis virus in tissue samples.
AB  - Hemorrhagic enteritis virus (HEV) is a type II avian adenovirus that causes
      intestinal hemorrhages accompanied with immunosuppression in 4-to-12-wk-old
      turkeys. In the present study, a hexon gene-based, quantitative real-time PCR
      with TaqMan probe was developed and applied to tissue samples from poultry farms
      to detect and quantify HEV genome copy numbers. The method was confirmed to be
      rapid, specific, and sensitive for the detection of HEV. This method is an
      excellent research and diagnostic tool that can be used to study pathogenesis and
      to gain insights into different phases of infection on poultry farms and for high
      throughput epidemiologic investigations.

PMID- 24689191
TI  - Genetic and antigenic variation of shedding viruses from vaccinated chickens
      after challenge with virulent Newcastle disease virus.
AB  - Newcastle disease virus (NDV) isolation was attempted from La Sota-vaccinated or
      unvaccinated chickens exposed to the virulent NDV variant E347Kmt. Shedding
      viruses were purified by plaque assay and then were sequenced for HN and F genes.
      The amino acid sequences of the F gene of all shedding viruses were identical to
      the sequence of the challenge virus. However, amino acid substitution occurred at
      four positions (70, 347, 466, and 517) in the HN protein among shedding viruses
      from vaccinated and challenged chickens but not from unvaccinated and challenged
      chickens. Amino acid substitution occurred more frequently at position 347 (K to
      G or V) in the HN protein compared with the other positions. There was minor
      antigenic variation between some of mutant viruses shed and challenge virus.
      However, none of mutant viruses had a significantly lower antigenic R value with
      La Sota virus compared with challenge virus E347Kmt. Our findings indicate that
      vaccinal immunity might facilitate an evolutional event through antigenic
      selection, genetic mutation among virulent virus populations shed from vaccinated
      flocks, or both.

PMID- 24689192
TI  - Development of a PCR for identification of Bordetella hinzii.
AB  - Bordetella hinzii infects primarily poultry and immunocompromised humans. It is
      closely related to the etiologic agent of turkey coryza, Bordetella avium.
      Distinguishing between B. avium and B. hinzii is difficult, and there is no
      method for identification of B. hinzii suitable for use by diagnostic
      laboratories. This report details the development of a B. hinzii-specific PCR
      targeting the ompA gene. Assay sensitivity is 100% based on analysis of 48 B.
      hinzii isolates from diverse geographic locations representing all known
      ribotypes. Evaluation of 71 isolates of B. avium and 20 other bacterial isolates
      from poultry, comprising gram-negative and gram-positive commensals and pathogens
      of nine genera, demonstrated an assay specificity of 100%. The ompA PCR is a
      rapid, reliable, and accurate method for identification of B. hinzii and provides
      a valuable new tool for veterinary diagnostic laboratories investigating poultry
      respiratory disease outbreaks.

PMID- 24689193
TI  - Causes of mortality in backyard chickens in northern California: 2007-2011.
AB  - A 5-yr retrospective study was conducted to characterize the spectrum of diseases
      causing mortality in 1301 backyard chickens submitted to the California Animal
      Health and Food Safety laboratory in Davis, California. Infectious diseases were
      diagnosed in the majority (60.4%). Viral diseases comprised 50% of the infectious
      entities, followed by bacterial diseases with an incidence of 39%. Marek's
      disease in the viral group and Escherichia coli in the bacterial group were the
      most commonly diagnosed infectious diseases. Zoonotic agents including
      Aspergillus sp., Salmonella sp., Listeria sp., Mycobacterium sp., Candida sp.,
      and Baylisascaris sp. were detected in 46 (3.5%) birds. Among noninfectious
      conditions, fatty liver hemorrhagic syndrome and reproductive tract
      adenocarcinoma were the leading causes of mortality. This analysis provides an
      overview of backyard chicken diseases for practitioners and avian pathologists
      working with backyard poultry. In addition, this study illustrates that backyard
      chickens do not seem to pose a major risk to public health, although zoonoses do
      comprise a notable portion (5.9% of all infectious cases) of isolated agents.

PMID- 24689194
TI  - Isolation of a virulent Newcastle disease virus from confiscated LaSota vaccine.
AB  - Vials of Newcastle disease vaccine labeled as LaSota were confiscated by the
      Arizona Division of Customs and Border Protection officials. Two different avian
      type 1 paramyxoviruses were isolated from all three vials of vaccine submitted to
      the National Veterinary Services Laboratories. The LaSota strain of avian
      paramyxovirus type 1 virus was isolated from all three vials and analyzed by
      nucleotide sequence analysis. A virulent Newcastle disease virus was also present
      in all three vials, but in low concentration. The virulence of the Newcastle
      disease virus was characterized by the intracerebral chicken pathogenicity index
      chicken inoculation assay but could not be determined by nucleotide sequence
      analysis from the virus isolated from embryonating chicken eggs. The
      intracerebral chicken pathogenicity index value for the isolated Newcastle
      disease virus was 1.55. Strains of Newcastle disease virus with intracerebral
      pathogenicity indexes significantly above 1.0 have been found to selectively kill
      many types of cancer cells while not affecting normal nonneoplastic cells and are
      considered to be a viable option for cancer treatment in humans by alternative
      medical researchers; however, the treatment is not approved for use in the United
      States by the Food and Drug Administration. Customs and Border Protection
      officials have been notified of an increased risk of Newcastle disease virus
      entering the United States for use as a nonapproved cancer treatment. Illegal
      importation of Newcastle disease vaccine for vaccination of backyard poultry is
      also a threat. This case report emphasizes the importance of conducting chicken
      inoculation for complete virus pathotyping and demonstrates the need for
      stringent security procedures at U.S. borders to detect known livestock pathogens
      that may be smuggled in for use in animal agriculture and reasons unrelated to
      animal agriculture.

PMID- 24689196
TI  - Foreword. Terpenes and terpenoids.

PMID- 24689195
TI  - Reovirus infections in young broiler chickens.
AB  - Selected 10-to-21-day-old broiler chickens from flocks undergoing runting
      stunting syndrome were found to have significant pancreatic damage, grossly and
      histologically. Six reoviruses, with sequences that varied, both from each other
      and from S1133 reovirus, were isolated from these pancreases and from pancreases
      of specific-pathogen-free leghorn sentinels placed on two of the broiler farms
      for 7 days.

PMID- 24689197
TI  - An expedient synthesis of linden ether.
AB  - We here describe a comprehensive study on the preparation of the intensive flavor
      3,9-epoxy-p-mentha-1,4(8)-diene (1). Key steps of the presented synthesis are the
      selective addition of MeLi to the keto-ester 7, the regioselective cyclization of
      the obtained triol to give the ethers 4 and 8 and the selective dehydration of
      ether 4 through the use of POCI3 and pyridine. It is worth noting that the
      presented synthesis represents the first expedient and reliable entry to ether 1.
      Being present in linden honey, 1 is also known as linden ether and it has been
      regarded as a potential marker for the authentication of the linden honey origin.
      Therefore, ether 1 can be used as a useful reference standard for the analysis of
      the natural flavors, as we demonstrated by means of its identification in a
      sample ofunifloral linden honey.

PMID- 24689198
TI  - Simple and short synthesis of trans-(R)-nerolidol, a pheromone component of fruit
      spotting bug.
AB  - A three-step synthesis of enantiomerically pure (R) and (S)-trans nerolidol from
      commercially available E,E-fanesol is described. Trans nerolidol is an abundant
      sesquiterpene in many plant species, almost enantiomerically pure; however, the
      configuration of chirality is S. There is no natural resource for R-trans
      nerolidol, which has recently been identified as a pheromone component of the
      fruit spotting bug Amblypelta lutescens. The simple syntheses reported here will
      make enantiomerically pure R- and S-trans nerolidol and homologues available for
      further research and ultimately for use in integrated pest management strategies
      comprising pheromones.

PMID- 24689199
TI  - Monoterpene citral derivatives as potential antimalarials.
AB  - Conjugated acid derivatives containing nitrogen have been synthesized from the
      simple acyclic monoterpene citral, using various reactions, including Wittig,
      Baylis Hillman, amide and ester condensations. Similarly, amine peroxides were
      synthesized by subjecting citral to Mannich type reaction with amines and t-butyl
      hydroperoxide. Molecules 3-10 were evaluated for antimalarial activity against
      erythrocytic stages of chloroquine sensitive P. falciparum strain 3D7. Four
      derivatives displayed interesting activity with an IC50< 2.5 microM, and warrant
      further investigations.

PMID- 24689200
TI  - A general synthetic approach to hydroquinone meroterpenoids: stereoselective
      synthesis of (+)-(S)-metachromin V and alliodorol.
AB  - A new general synthetic approach to hydroquinone meroterpenoids is here
      described. The framework of the aforementioned natural compounds was built up
      through the Li2CuCl4 catalysed cross coupling reaction of the 4-substituted-(E)
      prenyl acetates 9 with 2,5-bis(benzyloxy)phenyl magnesium bromide 8 as a key
      step. The latter sp3-sp2 coupling affords the products in good chemical yields
      and in very high stereoisomeric purity. A further key step of the present
      synthetic method consists of the removal of the benzylic protecting groups by a
      very mild procedure based on the use of lithium naphthalenide. The latter
      reagent, in combination with aliphatic dialkylamines, is able to cleave all the
      benzylic protecting groups leaving unaffected the polyenic moieties. By these
      means, we devised a new synthesis of the natural hydroquinone
      geranylhydroquinone, farnesylhydroquinone, metachromin V and alliodorol. In
      addition, the marine meroterpenoid, (+)-(S)-metachromin V, was synthesized for
      the first time; its chemical structure was confirmed and its absolute
      configuration was unambiguously assigned.

PMID- 24689201
TI  - Synthetic approach to the psoracorylifols.
AB  - Core analogs of the psoracorylifols were generated by a five-step route from 2,2
      dimethyl-4-cyanobutanal.

PMID- 24689202
TI  - Chemotaxonomic value of magastigmane glucosides of Cichorium calvum.
AB  - Morphological characters and molecular analyses of Cichorium calvum and C.
      pumilum do not allow clear discrimination between these closely related wild
      species. Therefore, the aim of this study was to characterize the secondary
      metabolites of C. calvum and to select chemical markers which are unique to this
      species. From roots of C. calvum, ten sesquiterpene lactones were isolated,
      including seven lactucin-type guaianolides reported earlier from C. pumilum.
      Aerial parts also afforded secondary metabolites common to both species, along
      with the megastigmane glucosides staphylionoside D, saussureoside B and
      komaroveside A. This is the first report of the occurrence of these
      norisoprenoids in Cichorium species and the second record of their isolation from
      plants. Therefore, chemical discrimination of C. calvum is possible on the basis
      of its norisoprenoid composition.

PMID- 24689203
TI  - Cyclonerol derivatives from Trichoderma longibrachiatum YM311505.
AB  - A new sesquiterpene, 10,11-dihydrocyclonerotriol (1), together with two known
      compounds, catenioblin C (2) and sohirnone A (3), were isolated from Trichoderma
      longibrachiatum YM311505, an endophytic fungus of Azadirachta indica. Their
      structures were characterized and identified by spectral analysis. Compounds 1-3
      exhibited antifungal activities against Pyricularia oryzae and Candida albicans.

PMID- 24689204
TI  - Anti-influenza sesquiterpene from the roots of Reynoutria japonica.
AB  - One new flavonol glycoside, 4'-O-methylmyricitrin 3'-O-beta-D-glucopyranoside
      (1), one new sesquiterpene, reynoudiol (11), as well as the 12 known compounds (2
      10, 12-14) quercetin 3-O-methyl ether (2), quercitrin (3), isorhamnetin 3-alpha-L
      rhamnopyranoside (4), tamarixetin 3-alpha-L-rhamnopyranoside (5), myricitrin (6),
      4'-O-methylmyricitrin (7), isorhamnetin 3-O-beta-D-xylopyranosyl (1-2)-O-beta- D
      glucopyranoside (8), isorhamnetin 3-O-beta- D-apiofuranosyl(1-2)-O-beta- D
      glucopyranoside (9), (+)-catechin (10), 7-drimene-3,11,12-triol (12), clovane-2
      beta,9 alpha-diol (13), and a-cadinol (14), were isolated from the methanol
      extract of Reynoutria japonica roots. Based on in vitro screening of the anti
      influenza activity of the isolated compounds, reynoudiol showed significantly
      higher activity than that of oseltamivir phosphate at the same concentration, and
      did not induce any detectable cytopathic effect in MDCK cells. The CC50 of
      reynoudiol was above 50 micro M and could inhibit influenza virus infection with
      an IC50 of 0.29 +/- 0.01 microM. The therapeutic index (TI) of reynoudiol against
      influenza infection was 172.4, and thus, this compound can be potentially used to
      treat oseltamivir-resistant influenza virus infection.

PMID- 24689205
TI  - Lactarane sesquiterpenes from the European mushrooms Lactarius aurantiacus, L.
      subdulcis, and Russula sanguinaria.
AB  - The results of the first investigation of secondary metabolites occurring in
      intact and damaged fruiting bodies of the European mushrooms Lactarius
      aurantiacus, L. subdulcis, and Russula sanguinaria are reported. The pattern of
      sesquiterpenes in injured R. sanguinaria is dramatically different from that of
      Lactarius. The structure of the new furanolactarane 4, isolated from L.
      aurantiacus, was established on the basis of spectral data.

PMID- 24689207
TI  - The first isolation of furanoeremophilane from Ligularia nelumbifolia.
AB  - Ligularol (1), a furanoeremophilane, was isolated together with eremophil-l(10)
      en-11-ol (2) from one of eight collected samples of Ligularia nelumbifolia and L.
      kongkalingensis, a closely related species. It is proposed that the ability to
      produce the furanoeremophilane has been acquired through hybridization.

PMID- 24689206
TI  - Laurane-, cyclolaurane-, and cuparane-type sesquiterpenes from the marine red
      alga Laurencia okamurai.
AB  - Chemical investigation of the secondary metabolites extracted from the marine red
      alga Laurencia okamurai has resulted in the isolation of one new (lauramurin, 1)
      and six known (2-7) sesquiterpenes. On the basis of the data obtained by our
      detailed spectroscopic analysis as well as by comparison with those reported, the
      structures of these compounds were elucidated as four laurane sesquiterpenes
      including lauramurin (1), laur-11-en-10-ol (2), aplysinol (3), and
      debromoaplysinol (4), two cyclolaurane sesquiterpenes laurequinone (5) and
      laurentristich-4-ol (6), and one cuparane ether sesquiterpene (7). The
      antibacterial activity against Staphylococcus aureus and brine shrimp (Artemia
      salina) lethality for the isolated compounds were evaluated. Compounds 2 and 5-7
      displayed moderate lethality against brine shrimp.

PMID- 24689208
TI  - Use of (S)-trans-gamma-monocyclofarnesol as a useful chiral building block for
      the stereoselective synthesis of diterpenic natural products.
AB  - A comprehensive study of the exploitation of (S)-trans-gamma-monocyclofarnesol as
      a useful chiral building block for the stereoselective synthesis of natural
      diterpene derivatives is here described. The farnesol derivative (+)-1 was used
      as starting material in the preparation of the diterpenes (S)-dehydroambliol-A
      and (S)-trixagol, as well as for the syntheses of the dinorditerpene (S)
      dinortrixagone and of the guanidine-interrupted terpenoid (S)-dotofide. Key steps
      of the presented syntheses were the cross-coupling between an allyl acetate and a
      Grignard reagent, the Wittig reaction, the selective preparation ofa
      diacylguanidine derivative and the alkylation of a sulfone derivative, followed
      by the reductive removal of the same functional group. It is worth noting that
      the natural products (+)-8, (+)-12 and (+)-15 were prepared stereoselectively for
      the first time, thus allowing the unambiguous assignment of their absolute
      configuration.

PMID- 24689209
TI  - Bioactivity-guided isolation of antiproliferative compounds from the roots of
      Onopordum acanthium.
AB  - Onopordum acanthium has been considered in traditional medicine to be effective
      against different cancers. The chloroform extracts of the root, which displayed
      antiproliferative effect against human tumor cell lines, was subjected to
      bioactivity-guided multistep chromatographic separation. This experiment resulted
      in the isolation of the sesquiterpene lactones 4beta,14-dihydro-3
      dehydrozaluzanin C (1), zaluzanin C (2) and 4beta,15,11beta,13
      tetrahydrozaluzanin C (3), the neolignan nitidanin-diisovalerianate (4), besides
      13-oxo-9Z,11 E-octadecadienoic acid (5), 24-methylenecholesterol (6), alpha
      linolenic acid, linoleic acid, stigmasterol and beta-sitosterol. The structures
      of the isolated compounds were established through analytical data (NMR, MS), and
      by comparison of these with those reported in the literature. All the
      aforementioned compounds were detected for the first time from this plant. The
      antiproliferative activities of compounds 1-6 were assessed on cervix
      adenocarcinoma HeLa, breast adenocarcinoma MCF7 and skin epidermoid carcinoma
      A431 cells by using the MTT assay. It was found that, 4beta,14-dihydro-3
      dehydrozaluzanin C (1), the most active antiproliferative compound of the
      extract, exerted remarkable tumor cell growth inhibitory activity (IC50 2.7-15.1
      microM).

PMID- 24689210
TI  - Distribution of (-)-hamanasic acid A in South American species of Flourensia and
      phytotoxic effects of leaf aqueous extracts.
AB  - The presence of the phytotoxic sesquiterpene (-)-hamanasic acid A {(-)HAA; 7
      carboxy-8-hydroxy-1(2), 12(13)-dien-bisabolene} isolated from Flourensia
      campestris (FC), was investigated in the South American species of the genus,
      together with the evaluation of the phytotoxic activity of their leaf aqueous
      extracts. (-)HAA was identified and isolated from F. fiebrigii (FF) and F.
      oolepis (FO), being chemically (GC-MS, NMR, [a]) and biologically (bioassayed on
      lettuce) indistinguishable from that of FC, while no (-)HAA was found in F. hirta
      (FH), F. riparia (FR) and F. niederleinii (FN). Its leaf content in FF was
      similar to that found in FC (ca. 15 mg g-1 WT) and significantly higher than in
      FO (0.8 mg g-1 WT). The screening for the presence of (-)HAA in other species of
      Flourensia communities showed that its natural occurrence is restricted only to
      Flourensia species. No (-)HAA could be detected in any of the 37 -most
      representative- species of these communities (26 natives, 11 exotics), despite
      many of them belong to the same family and tribe as Flourensia spp. Leaf aqueous
      extracts of all Flourensia species exhibited strong inhibitory effects on lettuce
      germination and on root and shoot growth, regardless of the presence and content
      of (-)HAA. These results strongly suggest the existence of other powerful
      phytotoxic compounds in those Flourensia spp lacking (-)HAA. Our results clearly
      show that (-)HAA only pertains to some species of the genus Flourensia. Relative
      to previous exomorphologic groupings of the genus, our chemotaxonomic data would
      give support to the close link described between FC and FF, but not with FR. In
      addition, the fact that (-)HAA was also found in FO, which belongs to a second
      different line, also points out that species position in this lineage would
      deserve to be revisited. The restricted production of (-)HAA by Flourensia in
      their communities suggests its special link with the genus, and sustains its
      putative allelochemical role.

PMID- 24689211
TI  - Neo-clerodane diterpenoids from Scutellaria galericulata.
AB  - Four neo-clerodane diterpenoids, neoajugapyrin A, scutegalerins A and B and
      scutecolumnin C have been isolated from the acetone extract of the aerial parts
      of Scutellaria galericulata. Neoajugapyrin A and scutecolumnin C are reported in
      this species for the first time, whereas scutegalerins A and B are new compounds.
      NMR data of neoajugapyrin A ar e discussed i n detail t o support t he proposed
      revised structure of ajugapyrin A.

PMID- 24689212
TI  - Seed dormancy breaking diterpenoids, including novel brassicicenes J and K, from
      fungus Alternaria brassicicola, and their necrotic/apoptotic activities in HL-60
      cells.
AB  - To find new metabolites similar to cotylenins and fusicoccins from the fungus
      Alternaria brassicicola, screening tests were carried out using the lettuce seed
      dormancy breaking assay. Activity-guided fractionation of the EtOAc extract from
      the culture using the assay afforded the isolation of two novel fusicoccane
      diterpenoids named brassicicenes J (1) and K (2), along with three known
      brassicicenes A (3), B (4), and F (5). Their structures were elucidated from
      extensive NMR spectral data and by comparison of these with those reported in the
      literature. Brassicicenes (1-5) exhibited weak to moderate seed dormancy breaking
      activities against lettuce seeds in the presence of abscisic acid. In addition,
      the necrotic/apoptotic activities of the brassicicenes (1-5), fusicoccin A (6)
      and cotylenin A (7) were evaluated by determining their cytotoxicity, cell
      viability and caspase-3/7 activation on the HL-60 cell line. Brassicicene K (2)
      exhibited similar cytostatic profiles to that of cotylenin A (7), and
      brassicicenes J (1), A (3), B (4), and F (5) exhibited necrotic activity. This is
      the first report of the seed dormancy breaking activity of brassicicenes in
      plants, and of necrotic/apoptotic activity in mammalian cells.

PMID- 24689213
TI  - Facile access to optically active ring C aromatic diterpene derivatives from (+)
      manool. first synthesis of 13,14-dihydroxy8,11,13-podocarpatrien-7-one.
AB  - 14,15,17-Trinorlabdan-8,13-dione 6 was efficiently synthesized via ozonolysis
      of(+)-manool (4) followed by treatment with aqueous NaOH in the presence of tetra
      n-butylammonium bromide as catalyst. This protocol has the advantages of high
      yield, mild conditions and simple procedure. Utilizing this strategy, the first
      enantiospecific synthesis of 13,14-dihydroxy-8,11,13-podocarpatrien-7-one (1), a
      constituent of Taiwania cryptomerioides and Celastrus paniculatus, was achieved
      starting from (+)-manool (4) after a four-step sequence in 24% overall yield.

PMID- 24689214
TI  - Antiproliferative effects of 12-oxoheteronemin vs heteronemin.
AB  - The antiproliferative activities of 12-oxoheteronemin and heteronemin were
      evaluated in six cancer cell lines and IC50 values ranging from 0.66 to 1.35
      microM were obtained. In four of the cell lines, 12-oxoheteronemin and
      heteronemin were equipotent; however, in two estrogenic receptor-positive cell
      lines, heteronemin showed a stronger potency. Both compounds had no overt effects
      on cell cycle distribution in HeLa cells, but did rapidly initiate apoptosis as
      evidenced by increased sub-G1 populations of cells and caspase-dependent PARP
      cleavage.

PMID- 24689215
TI  - New cembranoids from the soft coral Sinularia arborea.
AB  - From the ethyl acetate extract of the soft coral Sinularia arborea, a new
      cembrane-type diterpenoid, arbolide C (1), along with (+)-sarcophytol T (2), an
      enantiomer of the known cembrane, sarcophytol T, were isolated. The structures of
      compounds 1 and 2 were established by spectroscopic methods and 1 was found to
      display an inhibitory effect on the release of elastase by human neutrophils.

PMID- 24689216
TI  - T-DNA insertion alters the terpenoid content composition and bioactivity of
      transgenic Artemisia annua.
AB  - In this study, the interference of T-DNA insertion upon Agrobacterium-mediated
      transformation on the biochemical expression of the host genome is discussed.
      Plant extracts of transgenic Artemisia annua L. with or without an overexpressed
      famesyl pyrophosphate synthase gene have been investigated for their bioactivity
      and metabolic profile in comparison with wild type A. annua. The highest
      antimicrobial activity against Staphylococcus aureus, Bacillus subtilis and
      Candida albicans was observed in the T253 transgenic lines. Moreover, the crude
      extract from T253 showed higher antimalarial activity against the Plasmodium
      faciparum K1 strain than those of the others. The terpenoid constituents and
      antimicrobial properties of the plant samples were grouped by hierarchical
      clustering analysis. The clustering showed that squalene is a putative compound
      that might be involved in increasing the bioactivity of the transgenic line. In
      addition, T253 had a triterpene content that was about twice as great as that of
      the T253-2 line, which had a higher content of sesquiterpenes. However, both
      lines were transformed by the same FPS gene. These results suggested that the
      different bioactive properties observed in each transgenic line may be caused by
      variations in their terpenoid composition, which is affected by T-DNA insertion
      at different positions in the host plant.

PMID- 24689217
TI  - A new cytotoxic tirucallane from the twigs of Walsura trichostemon.
AB  - A new tirucallane, trichostemonol (1), together with five known compounds (2-6)
      were isolated from the twigs of Walsura trichostemon. The structures of the
      isolated compounds were determined by extensive analysis of their spectroscopic
      data. All isolated compounds were evaluated for their cytotoxicity against KB and
      HeLa cells.

PMID- 24689218
TI  - A new ergostane triterpenoid from cultures of the basidiomycete Inocybe lilacina.
AB  - A new ergostane triterpenoid (4 alpha-methylergost-8,24(28)-dien-3,7,1 1-trione,
      1) together with four known compounds (2-5) were isolated from cultures of the
      spectroscopic and M Sexperiments. basidiomycete Inocybe lilacina. The structure
      of the new compound was established on the basis of IR, 1D and 2D NMR

PMID- 24689219
TI  - New ursane triterpene from the fruits of Terminalia arjuna.
AB  - A new ursane triterpene, torment (2 alpha,3 beta,19 alpha-trihydroxyurs-12-en)
      (1), was isolated from the fruits of Terminalia arjuna along with four known
      ursane and oleane triterpenes. The structures were established on the basis of
      extensive NMR (1D & 2D) and MS (EI & ESI) studies. Tormentic acid (2), 19 alpha
      hydroxy asiatic acid (3) and olean-12-en-2 alpha,3 beta-diol (4) were isolated
      for the first time from this species. Compounds 1 and 2 lacked significant enzyme
      inhibition, cytotoxicity, immunomodulatory and antiglycation activities.

PMID- 24689220
TI  - New schiartane-type triterpene from Kadsura heteroclita and their cytotoxic
      activities.
AB  - One new schiartane-type triterpene, heteroclitalactone N (1), and four known
      compounds (2-5), seco-coccinic acid F, dihydroguaiaretic acid, schizanrin F, and
      kadsuralignan B were isolated from the stems of Kadsura heteroclita. Their
      structures were determined by the combination of spectroscopic and chemical
      methods, including 1D-, 2D-NMR, and CD spectra as well as by comparing with the
      NMR data reported in the literature. The cytotoxic activities of all isolated
      compounds were evaluated on three human cancer cell lines. Compound 3 exhibited
      moderate to weak cytotoxic activities on three human cancer cell lines, OVCAR, HT
      29, and A-549, with IC50 values ranging from 16.2 to 36.4 microM.

PMID- 24689221
TI  - C-lactam derivatives of oleanolic acid. hydrolysis and further acylation of
      methyl acetyloleanolate C-lactam and C-thiolactam.
AB  - Acetyl methyl oleanolate was transformed into a seven-membered C-lactam
      derivative (2) using Beckmann rearrangement of the corresponding C-oxime during
      the last step of the synthesis. The C=O group of the lactam system was
      transformed into a C=S group by Lavesson's reagent. The resulting
      acetylthiolactam 3 and initial acetyllactam 2 were subjected to alkaline
      hydrolysis to obtain lactam 4 and thiolactam 5 with an unsubstituted C-3 hydroxyl
      group. Subsequently, compounds 4 and 5 were acylated with either succinic or
      acetic anhydride in pyridine. Various acylating conditions were tested for
      hydroxythiolactam 5. The structures of the newly obtained compounds were
      supported by spectral and mass spectrometric data.

PMID- 24689222
TI  - New acylated triterpene glycosides from the roots of Polygala tenuifolia.
AB  - Two new and five known acylated triterpene glycosides were isolated from the MeOH
      extract of the roots of Polygala tenuifolia. Based on extensive spectroscopic
      analysis, including 2D NMR experiments, and the results of alkaline hydrolysis,
      the structures of the new compounds were assigned as 3beta-[(beta-D
      glucopyranosyl)oxy]-2 beta,27-dihydroxyolean- 12-ene-23,28-dioic acid 28-O-beta-D
      apiofuranosyl-( 1--3)-[beta-D-galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-(1 
      4)]-alpha-L-rhamnopyranosyl-(1-2)-3-O-(E)-3,4,5-trimeth oxycinnamoyl-beta-D
      fucopyranosyl ester (1) and 3beta-[(beta-D-glucopyranosyl)oxy]-2beta,27
      dihydroxyolean-1 2-ene-23,28-dioic acid 28-O-beta-D-apiofuranosyl-(l---3)-[beta-D
      galactopyranosyl-(1-->4)-beta-D-xylopyranosyl-( 1-->4)]-alpha-L-rhamnopyranosyl
      (1 -2)-[alpha-L-rhamnopyranosyl-( 1 -3 )]-4-O-(E)-3,4-dimethoxycinnamoyl-beta-D
      fucopyranosyl ester (2).

PMID- 24689223
TI  - Cucurbitane-type triterpene glycosides from the fruits of Momordica charantia.
AB  - Four new cucurbitane-type triterpene glycosides, charantosides D-G (1-4) were
      isolated from a methanol extract of Momordica charantia fruits. The structures of
      these compounds were determined by chemical and spectroscopic methods to be (19R)
      5 beta,19-epoxy-25-methoxycucurbita-6,23-diene-3 beta,19-diol 3-O-beta-D
      glucopyranoside, (19R)-5 beta, 19-epoxy-25-methoxycucurbita-6,23-diene-3 beta,19
      diol 3-O-beta-D-allopyranoside, 7 beta-methoxycucurbita-5,23E,25-triene-3 beta-ol
      3-O-beta-D-allopyranoside, and 3 beta,7 beta-dihydroxycucurbita-5,23E,25-triene-
      19-al 3-O-beta-D-allopyranoside.

PMID- 24689224
TI  - Cytotoxic effects of four aescin types on human colon adenocarcinoma cell lines.
AB  - Four types of aescin that are available on the pharmaceutical market, beta-aescin
      crystalline, beta-aescin amorphous, beta-aescin sodium and aescin polysulfate,
      have been analyzed for their cytotoxic effects on human colon adenocarcinoma
      (LoVo) and doxorubicin-resistant human colon adenocarcinoma cell lines (LoVo/Dx).
      Their cytotoxic activities were evaluated by sulforhodamine B (SRB) and methyl
      tetrazolium (MTT) assays. All four types of aescin exerted strong dose-dependent
      cytotoxicity to LoVo and, to a lesser degree, LoVo/Dx cell lines. The IC50 value
      for the LoVo/Dx cell line was higher, but still dose-dependent. Results from both
      assays demonstrated that p-aescin crystalline has the most cytotoxic activity
      toward human colon adenocarcinoma cell lines.

PMID- 24689225
TI  - Structures of violaceusosides C, D, E and G, sulfated triterpene glycosides from
      the sea cucumber Pseudocolochirus violaceus (Cucumariidae, Dendrochirotida).
AB  - Four new triterpene glycosides, violaceusosides C (1), D (2), E (3) and G (4)
      have been isolated from the sea cucumber Pseudocolochirus violaceus
      (Cucumariidae, Dendrochirotida). Eight known glycosides, DS-holothurin A and
      holothurinoside A, isolated earlier from Holothuria forskalii (order
      Aspidochirotida); and violaceuside A, lefevreoside C, philinopside E,
      intercedenside B, violaceuside II and liovilloside A isolated earlier from
      representatives of the family Cucumariidae, order Dendrochirotida have also been
      found in P. violaceus. The chemical structures of the glycosides were elucidated
      by 2D NMR spectroscopy and mass spectrometry. Violaceusosides C (1), D (2), E (3)
      and G (4) have holostane-type aglycones and tetrasaccharide linear carbohydrate
      chains differing in the sugar composition and the number and position of sulfate
      groups. Violaceusosides E (3) and G (4) are characterized by the presence of a
      sulfate group at C-3 of the quinovose residue that is very rare among sea
      cucumber glycosides. Cytotoxic activities of the glycosides 1-4 against cells of
      the ascite form of mouse Ehrlich carcinoma and hemolytic activities against mouse
      erythrocytes have been studied. Violaceusosides C (1) and D (2) demonstrated
      moderate cytotoxic and hemolytic effects, while violaceusosides E (3) and G (4)
      have more powerful activities.

PMID- 24689226
TI  - Phytotoxic terpenes produced by phytopathogenic fungi and allelopathic plants.
AB  - This review is about the isolation as well as chemical and biological
      characterization of simple and complex mono-, sesqui-, di-, sester- and tri
      terpenes produced by fungal pathogens of agrarian and forest plants and by some
      allelopathic plants. In several cases, the structure activity relationships are
      also discussed, as well as their potential application in agriculture as natural
      safe herbicides, fungicides and bactericides. Furthermore, the potential
      application of some fungal terpenes as anticancer compounds with a new mode of
      action is also discussed.

PMID- 24689227
TI  - Pungent and bitter, cytotoxic and antiviral terpenoids from some bryophytes and
      inedible fungi.
AB  - Most liverworts elaborate characteristic odiferous, pungent and bitter tasting
      compounds many of which show antimicrobial, antifungal, antiviral, allergenic
      contact dermatitis, cytotoxic, insecticidal, anti-HIV, superoxide anion radical
      release, plant growth regulatory, neurotrophic, NO production inhibitory, muscle
      relaxant, antiobesity, piscicidal and nematocidal activities. Several inedible
      mushrooms produce female spider pheromones, strong antioxidant, and cytotoxic
      compounds. The present paper is concerned with the extraction and isolation of
      terpenoids from some bryophytes and inedible fungi and their pungent and bitter
      taste, and cytotoxic and antiviral activity.

PMID- 24689228
TI  - Terpenoids and sterols from some Japanese mushrooms.
AB  - Over the past twenty years, our research group has been studying the chemical
      constituents of mushrooms. From nineteen species, namely, Amanita virgineoides
      Bas (Amanitaceae), Daedaleopsis tricolor (Bull.: Fr.) Bond. et Sing.
      (Polyporaceae), Grifolafrondosa (Fr.) S. F. Gray (Polyporaceae), Hericium
      erinaceum (Bull.: Fr.) Pers. (Hericiaceae), Hypsizigus marmoreus (Peck) Bigelow
      (Tricholomataceae), Lactarius piperatus (Scop.: Fr.) S. F. Gray (Russulaceae),
      Lentinula edodes (Berk.) Sing. (Pleurotaceae), Lyophyllyum connatum (Schum.: Fr.)
      Sing. (Tricholomataceae), Naematoloma sublateritium (Fr.) Karst.
      (Strophariaceae), Ompharia lapidescens Schroeter (Polyporaceae), Panellus
      serotinus (Pers.: Fr.) Kuhn. (Tricholomataceae), Pholiota nameko (T. Ito) S. Ito
      et Imai in Imai (Strophariaceae), Pleurotus eringii (DC.: Fr.) Quel.
      (Pleurotaceae), Polyporus umbellatus Fries (Polyporaceae), Russula delica Fr.
      (Russulaceae), Russula sanguinea (Bull.) Fr. (Russulaceae), Sarcodon aspratus
      (Berk.) S. Ito (Thelephoraceae), Tricholoma matsutake (S. Ito et Imai) Sing.
      (Tricholomataceae), and Tricholomaportentosum (Fr.) Quel. (Tricholomataceae), we
      isolated eight new sesquiterpenoids, six new meroterpenoids, three new
      triterpenoids, and twenty eight new sterols. In this review, structural features
      of these new compounds are discussed.

PMID- 24689229
TI  - Phytochemicals and biological activities of poisonous genera of Ericaceae in
      China.
AB  - The family Ericaceae is comprised of about 70 genera of which about 20 are found
      throughout China. Of these Ledum, Rhododendron, Enkianthus, Pieris,
      Craibiodendron, Gaultheria, Vaccinium, and Leucothoe are regarded as poisonous.
      Many species of these poisonous genera are used as Chinese herbal medicines for
      the treatment of, for example, inflammation, asthma, and coughs. Modem research
      has demonstrated that the toxic ingredients of these poisonous genera are chiefly
      tetracyclic diterpenes, which have adverse effects on the digestive,
      cardiovascular and nervous systems. Because various species of these poisonous
      genera also have medicinal functions, extensive studies of these plants have led
      to the identification of many kinds of compound. This paper compiles 306
      compounds from the eight poisonous genera, reported in 141 references.

PMID- 24689230
TI  - [Cyclooxygenases, lipoxygenases, their targeted drugs and the prevention of
      Alzheimer's disease].
AB  - Many studies have shown that chronic inflammation occurs in the brain of patients
      with Alzheimer's disease (AD). It is well known that long-term administration of
      non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive
      decline of AD patient and elderly. Several inflammatory cytokines produced in the
      metabolism of arachidonic acid (AA) are closely related to inflammatory diseases.
      Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA
      network, the products eicosanoids have an important impact on the progression of
      AD. Although there are many arguments and conflicting evidence, currently LOXs
      and COXs are still the hot topics in the research on AD pathogenesis and drug
      development. Here, we review the progress in research on COXs and LOXs, including
      their actions on CNS and their association with AD, and explore the feasibility
      of LOXs and COXs as targets for the drugs to prevent and/or treat AD.

PMID- 24689231
TI  - [Ligand efficiency and lead optimization].
AB  - Pharmacological activity and druggability are two pivotal factors in drug
      innovation, which are respectively determined by the microscopic structure and
      macroscopic property of a molecule. Since structural optimization consists in a
      molecular operation in the space with multi-dimensions, and there exists a body
      of uncertainties for transduction from in vitro activity into in vivo
      pharmacological response. It is necessary for early stage in lead optimization to
      evaluate compound quality or efficiency using a kind of metrics containing multi
      parameters. On the basis of the describing parameters of activity and
      druggability, this overview deals with the roles of thermodynamic signatures and
      binding kinetics of drug-receptor interactions in optimizing quality of
      compounds, signifying the significance in optimization of microscopic structures
      for drug discovery.

PMID- 24689232
TI  - [An overview of glycoconjugates for cancer targeting therapy and diagnosis].
AB  - Because of the changed metabolic behaviors of cancer cells, tumor cells uptake a
      corresponding larger amount of glucose in physiological condition when compared
      with normal cells. And they were prone to metabolize glucose for generating
      energy in anaerobic glycolysis ways in order to grow quickly. Anaerobic
      glycolysis consumes more glucose than aerobic way when the same amount of energy
      is obtained, which also results in large demand of glucose in tumor cells. This
      review briefly describes therapy methods related to characteristic mentioned
      above, and summarizes the research progress of drugs, diagnostic reagents and
      carriers conjugated with glucose, glucose derivatives or other kinds of sugars
      for cancer targeting. Furthermore, typically relative research reports from 2012
      till now were listed and analyzed.

PMID- 24689233
TI  - [Anticancer effect of 17-(6-cinnamamido-hexylamino-)-17-demethoxygeldanamycin: in
      vitro and in vivo].
AB  - In the present study, a new compound named 17-(6-cinnamamido-hexylamino-)-17
      demethoxygeldanamycin (CDG) was obtained by introducing the cinnamic acid (CA)
      group into the 17-site of geldanamycin (GDM). The anti-cancer effects of CDG in
      vitro and in vivo were evaluated. MTT assay was used to examine the inhibitory
      effect of CDG on the proliferation of MCF-7, HepG2, H460 and SW1990 cells.
      Immunofluorescent staining flow cytometry combined with Annexin V-FITC/PI
      staining were used to detect apoptotic cells. Transwell assay was used to analyze
      the effect of CDG on cell invasion and migration ability. Western blotting was
      used to detect the expression levels of RAF-1, EGFR, AKT, CDK4 and HER-2 of MCF
      7, HepG2 and H460 cells. The toxicities of CDG and GDM were evaluated in mice.
      Using the subcutaneously transplanted MCF-7 xenograft in nude mice, inhibitory
      effect was evaluated in vivo. The results showed that CDG inhibited the
      proliferation of cancer cells (IC50: 13.6-67.4 microg.mL-1). After exposure to
      CDG for 48 h, most cells presented typical morphologic changes of apoptosis such
      as chromatin condensation or shrunken nucleus. The rates of apoptosis of MCF-7,
      HepG2, H460 and SW1990 cells incubated with 10 microg.mL-1 CDG were 23.16%,
      27.55%, 22.21%, 20.47%, respectively. A dose-dependent reduction of migration of
      four cell lines was found after exposure to CDG. The decreased levels of RAF-1,
      EGFR, AKT, CDK4 and HER-2 showed that CDG possessed HSP90 inhibitory effect. The
      result of animal toxicity test on the mice suggested that CDG had lower toxicity
      than GDM. Meanwhile, CDG inhibited the growth of MCF-7 xenografts of athymic
      mice.

PMID- 24689234
TI  - [Therapeutic effect of fibroblast growth factor 21 on NAFLD in MSG-iR mice and
      its mechanism].
AB  - This study is to evaluate the therapeutic effect of fibroblast growth factor 21
      (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its
      therapeutic effect. The MSG-IR mice with insulin resistance were treated with
      high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21
      once a day for 5 weeks. Body weight was measured weekly. At the end of the
      experiment, serum lipids, insulin and aminotransferases were measured. Hepatic
      steatosis was observed. The expression of key genes regulating energy metabolism
      were detected by real-time PCR. The results showed that after 5 weeks treatment,
      both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia
      (P<0.01), reversed steatosis and restored the liver morphology in the MSG model
      mice and significantly ameliorated insulin resistance. Additionally, real-time
      PCR showed that FGF21 significantly reduced transcription levels of fat synthetic
      genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up
      regulating key genes of lipolysis, thereby liver fat accumulation was reduced and
      liver function was restored to normal levels. In conclusion, FGF21 significantly
      reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses
      hepatic steatosis. These findings provide a theoretical support for clinical
      application of FGF21 as a novel therapeutics for treatment of NAFLD.

PMID- 24689235
TI  - [Effect of piperine on 5-HT and synaptophysin expression of rats with irritable
      bowel syndrome].
AB  - This study is to explore the amelioration of piperine on chronic acute combining
      stress rat with depression-like behavior, visceral sensitivity, and its effect on
      the expression of serotonin (5-HT) and synaptophysin. Forty two SD rats were
      divided into seven groups: blank group, model group, piperine (12.5, 25, 50 and
      100 mgkg-1, ig) and imipramine (10 mgkg-1, ip) groups. The rat model of irritable
      bowel syndrome was established by chronic acute combining stress, and then to
      evaluate depression-like behavior and visceral sensitivity. The expressions of 5
      HT and synaptophysin in the hippocampus and colon were determined by high
      performance liquid chromatography (HPLC) and Western blotting, respectively. The
      duration of immobility of IBS rat in the forced swimming test had been
      significantly increased, the sucrose consumption of IBS rat had been reduced and
      visceral sensitivity was obviously elevated in the IBS model group as compared
      with those in the normal control group (P<0.05, P<0.01). As compared with those
      in the normal control group, the expression of 5-HT significantly decreased, 5
      HIAA/5-HT ratio significantly increased in the hippocampus of IBS model group
      (P<0.05), but opposite presentations were noted in the colon (P<0.05). As
      compared with that in the normal control group, the synaptophysin expression in
      the hippocampus decreased significantly but obviously increased in the colon
      (P<0.05). Piperine improved the behavior of IBS rats, and reversed the levels of
      5-HT and 5-HIAA, and 5-HIAA/5-HT proportion in the hippocampus and colon
      (P<0.05); besides, they significantly reverse the synaptophysin level in the
      hippocampus and colon (P<0.05). The presence of depression and visceral
      sensitivity had been changed in IBS rats, with abnormal expression of 5-HT and
      synaptophysin in the brain-gut system. Piperine can ameliorate the changes of the
      behavior and regulation of serotonin and synaptophysin expression in IBS rat
      model.

PMID- 24689236
TI  - [Synthesis and activity evaluation of PARP-1 inhibitors with azaindole skeleton].
AB  - PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer
      therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP
      ribose units from NAD to a number of its substrate proteins. In this work, a
      series of novel azaindole derivatives was designed and synthesized. Moreover, 16
      target molecules were screened and 8 compounds displayed inhibitory activity
      against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine
      substituents at 2-position were active to both PARP-1 and PARP-2.

PMID- 24689237
TI  - [Synthesis and structure-activity relationship of cycloberberine as anti-cancer
      agent].
AB  - A series of cycloberberine derivatives were designed, synthesized and evaluated
      for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e
      and 6g showed strong inhibition on human HepG2 cells. They afforded a potent
      effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism
      showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g
      using flow cytometry assay. It significantly inhibited the activity of DNA Top I
      at the concentration of 0.1 mg mL-1. Our results provided a basis for the
      development of this kind of compounds as novel anti-cancer agents.

PMID- 24689238
TI  - [Microcalorimetric investigation on the interaction of six alkaloids from rhizoma
      coptidis].
AB  - How to identify active constituents of traditional Chinese medicines (TCMs) and
      study their interactions are key problems in the development of TCMs. The
      inhibitory effect of six alkaloids from Rhizoma Coptidis (RC) on Shigella
      dysenteriae (S. dysenteria) growth had been investigated by microcalorimetry in
      this study. Main active constituents of RC were confirmed by comparing their
      contributions to the bacteriostatic effect, and the interactions among active
      constituents were further researched. According to the result, in 0.8 mg-mL-1
      extract of RC, the contributions of six active alkaloids including berberine,
      coptisine, epiberberine, palmatine and the combination of jatrorrhizine and
      columbamine were 52.83%, 36.31%, 2.49%, 4.27% and 3.21%, respectively. Therefore,
      berberine and coptisine were the main active constituents of RC that inhibited
      the growth of S. dysenteria. The study of interactions among the six alkaloids
      indicated that, 1 there were some contstituents antagonizing the inhibitory
      effect of RC, 2 there was a synergy effect between berberine and coptisine, 3
      there were additive effects between other four alkaloids and the main active
      constituents. These results may provide some useful references for the
      establishment of the quality standard for RC and the development of multi
      component TCMs.

PMID- 24689239
TI  - [Fragmentation behaviors of taxanes drugs using electrospray ionization with
      quadrupole time-of-flight mass spectrometry].
AB  - The fragmentation pathways of two taxanes drugs have been studied in positive ion
      mode by Q-TOF with the advantages of high mass accuracy and high resolution
      analysis. The [M+H] + ions were observed by ESI-MS, from which the molecular
      weights were obtained. Using the protonated pseudo-molecular ions [M+H]+ as
      internal reference compounds, the accurate mass and element composition of the
      fragment ions were determined. The collision induced dissociation (CID) data of
      the [M+H] ions provided fragmentation pathways of related compounds. Results
      showed that the major cleavage pathways of paclitaxel and docetaxel were the same
      that the cleavage of C-O bond between the side chain and taxol skeleton easily
      occurred, then stripping of the functional groups on the parent ring. Some common
      fragments were formed, such as m/z 105.033 7, 291.137 3, 309.148 5, 327.159 7,
      387.181 2 and 509.217 4, which would provide a basis for future qualitative and
      quantitative analysis of taxanes in vitro and in vivo.

PMID- 24689240
TI  - [Metabolism of naringin produced by intestinal bacteria].
AB  - Naringin has been reported to possess a wild range of biological activities.
      However, the route and metabolites of naringin produced by intestinal bacteria
      are not well understood. In this paper, different bacteria were isolated from
      human feces and their abilities to convert naringin to different metabolites were
      studied. Ultra performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry (UPLC-Q-TOF/MS) with automated data analysis software (MetaboLynx)
      was applied to fast analysis of naringin metabolites. Using MSE and mass defect
      filter techniques, three metabolites were detected and tentatively identified.
      The results indicated that acetylation, hydrolyzation and hydrolyzation with
      hydrogenation were the major metabolic pathways of naringin in vitro. Then, we
      studied the gene sequence of the 16S rRNA of the bacteria by extraction of
      genomic DNA of the strain, PCR amplification and clone of the 16S rRNA. The
      consequence proved that Enterococcus sp.30, Bacillus sp.46, Escherichia sp.54 and
      Escherichia sp.63 have the peculiar metabolism characteristic of naringin.

PMID- 24689241
TI  - [Metabolites and metabolic pathways of mesaconitine in rat liver microsomal
      investigated by using UPLC-MS/MS method in vitro].
AB  - Mesaconitine was incubated with rat liver microsomes in vitro. The metabolites of
      mesaconitine in rat liver microsomes were identified by ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) method with high resolution
      power. A typical reaction mixture of 100 mol L-1 Tris-HCI buffer (pH 7.4)
      containing 0.5 gL-1 microsomal protein and 50 micro molL-1 mesaconitine was
      prepared. The above reaction mixture was divided into six groups, and the volume
      of each group was 200 micro L. The incubation mixture was pre-incubated at 37
      degrees C for 2 min and the reactions were initiated by adding NADPH generating
      system. After 90 min incubation at 37 degrees C, 200 micro L of acetonitrile was
      added to each group to stop the reaction. The metabolites of mesaconitine were
      investigated by UPLC-MS/MS method. Mesaconitine and 6 metabolites M1-M6 were
      found in the incubation system. The structures were characterized according to
      the data from MS/MS spectra and literatures. The metabolic reactions of
      mesaconitine in rat liver microsomes included the demethylation, deacetylation,
      dehydrogenation and hydroxylation. The major metabolic pathways of mesaconitine
      in rat liver microsomes were determined by UPLC-MS/MS on multiple reaction
      monitoring (MRM) mode combined with specific inhibitors of cytochrome P450 (CYP)
      isoforms, including alpha-naphthoflavone (CYP1A2), quinine (CYP2D),
      diethyldithiocarbamate (CYP2E1), ketoconazole (CYP3A) and sulfaphenazole (CYP2C),
      separately. Mesaconitine was mainly metabolized by CYP3A. CYP2C and CYP2D were
      also more important CYP isoforms for the metabolism reactions of mesaconitine,
      but CYP1A2 and CYP2E1 haven't any contribution to MA metabolism in rat liver
      microsomes.

PMID- 24689242
TI  - [Transport of PLGA nanoparticles across Caco-2/HT29-MTX co-cultured cells].
AB  - The present study is to establish Caco-2/HT29-MTX co-cultured cells and
      investigate the transport capability of PLGA nanoparticles with different surface
      chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA
      NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using
      poly(lactic-co-glycolic acid) as carrier material with surface modified by
      methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential
      of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used
      as a fluorescent marker in the transport of nanoparticles investigated by
      confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded
      nanoparticles was quantitively determined by high performance liquid
      chromatography. Colchicine and nocodazole were used in the transport study to
      explore the involved endocytosis mechanisms of nanoparticles. Distribution of the
      tight junction proteins ZO-1 was also analyzed by immunofluorescence staining.
      The results showed that the nanoparticles dispersed uniformly. The zeta potential
      of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA
      NPs was positive. The entrapment efficiency of FDE in all nanoparticles was
      higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX
      co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine
      and nocodazole could significantly decrease the transport amount of
      nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1
      protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and
      mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular
      way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could
      shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles,
      which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result,
      mPEG-PLGA-NPs could penetrate the mucus layer rapidly and transport across Caco
      2/HT29-MTX co-cultured cells.

PMID- 24689244
TI  - [Preparation and in vitro evaluation of doxorubicin-loaded magnetic iron oxide
      nanoparticles].
AB  - PEG-modified magnetic Fe3O4 (Fe3O4-PEG) nanoparticles were sythesized using a
      solvothermal reaction and characterized with transmission electron microscopy
      (TEM) and thermo gravimetric analysis (TGA). The photothermal effect and
      photothermal destruction of cancer cells were evaluated. Then the doxorubicin
      loaded Fe3O4-PEG (DOX-Fe3O4-PEG) nanoparticles were prepared. The cytotoxicity
      and combined chemotherapy/photothermal therapy (PTT) effect were investigated.
      Uniform PEG coated Fe3O4 nanoparticles with particle size of 155 nm were obtained
      in the experiment. The loading and release of doxorubicin on Fe3O4-PEG were pH
      dependent. The drug loading capacity in water was 21%. The results of MTT
      indicated a good biocompatiblity of Fe3O4-PEG nanoparticles and high cytotoxicity
      of DOX-Fe3O4-PEG. In combined therapy experiment, photothermal therapy
      demonstrated unambiguously enhanced chemotherapy efficacy. In conclusion, the
      obtained Fe3O4-PEG nanoparticles which exhibit good photothermal effect and drug
      loading capacity can be used for chemotherapy and photothermal therapy. The
      synergetic anti-tumor activity indicates the potential for the combined
      application of chemotherapy and photothermal therapy in cancer treatment.

PMID- 24689243
TI  - [Rat intestinal absorption trait of peimine and peiminine in Thunberg fritillary
      bulb extract].
AB  - To study the in situ intestinal absorption kinetics and compatibility influence
      of peimine and peiminine in rats, the absorption of peimine and peiminine in
      small intestine (duodenum, jejunum and ileum) and colon of rats was investigated
      using in situ single-pass perfusion method and the drug content was measured by
      HPLC-ELSD. Perfusion rate, pH, concentration of drug, gender and bile duct
      ligation can significantly affect the absorption of peimine and peiminine, the
      Ka, and Papp values in the condition of pH 6.8 and pH 7.4 had significant
      difference (P<0.01), as drug concentration irlcreased, the absorption parameters
      of peimine and peiminine decreased, Ka and Papp between low concentrations and
      middle concentrations was significant difference (P<0.01). Verapamil can not
      affect Ka and Papp of peimine and peiminine which are in the extract (P> 0.05).
      Bitter almonds and licorice can significantly reduce the absorption of peimine
      and peiminine with the usual dose (P<0.01), extracted separately and together had
      no significant difference on Ka and Papp (P> 0.05). Experimental results show
      that the absorption features of peimine and peiminine are basically the same,
      both of them could be absorbed at all segments of the intestine in rats and had
      no special absorption window, and with significant differences between male and
      female individuals. The absorption of peimine and peiminine complies with the
      active transport and facilitated diffusion in the general intestinal segments.
      Bitter almond and licorice can reduce the intestinal absorption rate ofpeimine
      and peiminine.

PMID- 24689245
TI  - [Discussion on the botanical origin of Isatidis radix and Isatidis folium based
      on DNA barcoding].
AB  - This paper aimed to investigate the botanical origins of Isatidis Radix and
      Isatidis Folium, and clarify the confusion of its classification. The second
      internal transcribed spacer (ITS2) of ribosomal DNA, the chloroplast matK gene of
      22 samples from some major production areas were amplified and sequenced.
      Sequence assembly and consensus sequence generation were performed using the
      CodonCode Aligner. Phylogenetic study was performed using MEGA 4.0 software in
      accordance with the Kimura 2-Parameter (K2P) model, and the phylogenetic tree was
      constructed using the neighbor-joining methods. The results showed that the
      length of ITS2 sequence of the botanical origins of Isatidis Radix and Isatidis
      Folium was 191 bp. The sequence showed that some samples had several SNP sites,
      and some samples had heterozygosis sites. In the NJ tree, based on ITS2 sequence,
      the studied samples were separated into two groups, and one of them was gathered
      with Isatis tinctoria L. The studied samples also were divided into two groups
      obviously based on the chloroplast matK gene. In conclusion, our results support
      that the botanical origins of Isatidis Radix and Isatidis Folium are Isatis
      indigotica Fortune, and Isatis indigotica and Isatis tinctoria are two distinct
      species. This study doesn't support the opinion about the combination of these
      two species in Flora of China.

PMID- 24689246
TI  - Perfect timing: urgency, not driving situations, influence the best timing to
      activate warnings.
AB  - OBJECTIVE: The aim of the study was to investigate the influence of different
      driving scenarios (urban, rural, highway) on the timing required by drivers from
      a two-stage warning system, based on car-to-car communication. BACKGROUND: Car-to
      car communication systems are designed to inform drivers of potential hazards at
      an early stage, before they are visible to them. Here, questions arise as to how
      drivers acknowledge early warnings and when they should be informed (first stage)
      and warned (second stage). Hence, optimum timing for presenting the information
      was tested. METHOD: A psychophysical method was used to establish the optimum
      timing in three driving scenarios at different speed limits (urban: 50 km/h,
      rural: 100 km/h, highway: 130 km/h). A total of 24 participants (11 female, 13
      male; M = 29.1 years, SD = 11.6 years) participated in the study. RESULTS: The
      results showed that the optimum timing did not differ among the three
      scenarios.The first and second stages should ultimately be presented at different
      timings at each speed limit (first stage: 26.5 s, second stage: 12.1 s before a
      potential hazard). CONCLUSION: The results showed that well-selected timing for
      activating information and warning is crucial for the acceptance of these
      systems. Appropriate timing for presenting the information and warning can be
      derived for these systems. APPLICATION: The findings will be integrated in
      further development of assistance systems based on car-to-x technology within the
      Car2X-Safety project of the Niedersachsisches Forschungszentrum Fahrzeugtechnik
      in Germany.This study was also supported by Chalmers University of Technology in
      Sweden.

PMID- 24689247
TI  - Driving with the wandering mind: the effect that mind-wandering has on driving
      performance.
AB  - OBJECTIVE: The principal objective of the present work was to examine the effects
      of mind state (mind-wandering vs. on-task) on driving performance in a high
      fidelity driving simulator. BACKGROUND: Mind-wandering is thought to interfere
      with goal-directed thought. It is likely, then, that when driving, mind-wandering
      might lead to impairments in critical aspects of driving performance. In two
      experiments, we assess the extent to which mind-wandering interferes with
      responsiveness to sudden events, mean velocity, and headway distance. METHOD:
      Using a car-following procedure in a high-fidelity driving simulator,
      participants were probed at random times to indicate whether they were on-task at
      that moment or mind-wandering. The dependent measures were analyzed based on the
      participant's response to the probe. RESULTS: Compared to when on-task, when mind
      wandering participants showed longer response times to sudden events, drove at a
      higher velocity, and maintained a shorter headway distance. CONCLUSION:
      Collectively, these findings indicate that mind-wandering affects a broad range
      of driving responses and may therefore lead to higher crash risk. APPLICATION:
      The results suggest that situations that are likely associated with mind
      wandering (e.g., route familiarity) can impair driving performance.

PMID- 24689248
TI  - Shared leadership in multiteam systems: how cockpit and cabin crews lead each
      other to safety.
AB  - OBJECTIVE: In this study, we aimed to examine the effect of shared leadership
      within and across teams in multiteam systems (MTS) on team goal attainment and
      MTS success. BACKGROUND: Due to different and sometimes competing goals in MTS,
      leadership is required within and across teams. Shared leadership, the
      effectiveness of which has been proven in single teams, may be an effective
      strategy to cope with these challenges. METHOD: We observed leadership in 84
      cockpit and cabin crews that collaborated in the form of six-member MTS aircrews
      (N = 504) during standardized simulations of an in-flight emergency. Leadership
      was coded by three trained observers using a structured observation system. Team
      goal attainment was assessed by two subject matter experts using a checklist
      based rating tool. MTS goal attainment was measured objectively on the basis of
      the outcome of the simulated flights. RESULTS: In successful MTS aircrews, formal
      leaders and team members displayed significantly more leadership behaviors,
      shared leadership by pursers and flight attendants predicted team goal
      attainment, and pursers' shared leadership across team boundaries predicted cross
      team goal attainment. In cockpit crews, leadership was not shared and captains'
      vertical leadership predicted team goal attainment regardless of MTS success.
      CONCLUSION: The results indicate that in general, shared leadership positively
      relates to team goal attainment and MTS success,whereby boundary spanners' dual
      leadership role is key. APPLICATION: Leadership training in MTS should address
      shared rather than merely vertical forms of leadership, and component teams in
      MTS should be trained together with emphasis on boundary spanners' dual
      leadership role. Furthermore, team members should be empowered to engage in
      leadership processes when required.

PMID- 24689249
TI  - Development and validation of a multilevel model for predicting workload under
      routine and nonroutine conditions in an air traffic management center.
AB  - OBJECTIVE: The aim of this study was to develop a model capable of predicting
      variability in the mental workload experienced by frontline operators under
      routine and nonroutine conditions. BACKGROUND: Excess workload is a risk that
      needs to be managed in safety-critical industries. Predictive models are needed
      to manage this risk effectively yet are difficult to develop. Much of the
      difficulty stems from the fact that workload prediction is a multilevel problem.
      METHOD: A multilevel workload model was developed in Study I with data collected
      from an en route air traffic management center. Dynamic density metrics were used
      to predict variability in workload within and between work units while
      controlling for variability among raters.The model was cross-validated in Studies
      2 and 3 with the use of a high-fidelity simulator. RESULTS: Reported workload
      generally remained within the bounds of the 90% prediction interval in Studies 2
      and 3. Workload crossed the upper bound of the prediction interval only under
      nonroutine conditions. Qualitative analyses suggest that nonroutine events caused
      workload to cross the upper bound of the prediction interval because the
      controllers could not manage their workload strategically. CONCLUSION: The model
      performed well under both routine and nonroutine conditions and over different
      patterns of workload variation. APPLICATION: Workload prediction models can be
      used to support both strategic and tactical workload management. Strategic uses
      include the analysis of historical and projected workflows and the assessment of
      staffing needs.Tactical uses include the dynamic reallocation of resources to
      meet changes in demand.

PMID- 24689250
TI  - Identification of the human factors contributing to maintenance failures in a
      petroleum operation.
AB  - OBJECTIVE: This research aimed to identify the most frequently occurring human
      factors contributing to maintenance-related failures within a petroleum industry
      organization. Commonality between failures will assist in understanding
      reliability in maintenance processes, thereby preventing accidents in high-hazard
      domains. BACKGROUND: Methods exist for understanding the human factors
      contributing to accidents. Their application in a maintenance context mainly has
      been advanced in aviation and nuclear power. Maintenance in the petroleum
      industry provides a different context for investigating the role that human
      factors play in influencing outcomes. It is therefore worth investigating the
      contributing human factors to improve our understanding of both human factors in
      reliability and the factors specific to this domain. METHOD: Detailed analyses
      were conducted of maintenance-related failures (N = 38) in a petroleum company
      using structured interviews with maintenance technicians. The interview structure
      was based on the Human Factor Investigation Tool (HFIT), which in turn was based
      on Rasmussen's model of human malfunction. RESULTS: A mean of 9.5 factors per
      incident was identified across the cases investigated.The three most frequent
      human factors contributing to the maintenance failures were found to be
      assumption (79% of cases), design and maintenance (71%), and communication (66%).
      CONCLUSION: HFIT proved to be a useful instrument for identifying the pattern of
      human factors that recurred most frequently in maintenance-related failures.
      APPLICATION: The high frequency of failures attributed to assumptions and
      communication demonstrated the importance of problem-solving abilities and
      organizational communication in a domain where maintenance personnel have a high
      degree of autonomy and a wide geographical distribution.

PMID- 24689251
TI  - Measuring workload in collaborative contexts: trait versus state perspectives.
AB  - OBJECTIVE: In the present study, we explored the state versus trait aspects of
      measures of task and team workload in a disaster simulation. BACKGROUND: There is
      often a need to assess workload in both individual and collaborative settings.
      Researchers in this field often use the NASATask Load Index (NASA-TLX) as a
      global measure of workload by aggregating the NASA-TLX's component items. Using
      this practice, one may overlook the distinction between traits and states.
      METHOD: Fifteen dyadic teams (11 inexperienced, 4 experienced) completed five
      sessions of a tsunami disaster simulator. After every session, individuals
      completed a modified version of the NASA-TLX that included team workload
      measures.We then examined the workload items by using a between-subjects and
      within-subjects perspective. RESULTS: Between-subjects and within-subjects
      correlations among the items indicated the workload items are more independent
      within subjects (as states) than between subjects (as traits). Correlations
      between the workload items and simulation performance were also different at the
      trait and state levels. CONCLUSION: Workload may behave differently at trait
      (between-subjects) and state (within-subjects) levels. APPLICATION: Researchers
      interested in workload measurement as a state should take a within-subjects
      perspective in their analyses.

PMID- 24689252
TI  - Team knowledge representation: a network perspective.
AB  - OBJECTIVE: We propose a network perspective of team knowledge that offers both
      conceptual and methodological advantages, expanding explanatory value through
      representation and measurement of component structure and content. BACKGROUND:
      Team knowledge has typically been conceptualized and measured with relatively
      simple aggregates, without fully accounting for differing knowledge
      configurations among team members. Teams with similar aggregate values of team
      knowledge may have very different team dynamics depending on how knowledge
      isolates, cliques, and densities are distributed across the team; which members
      are the most knowledgeable; who shares knowledge with whom; and how knowledge
      clusters are distributed. METHOD: We illustrate our proposed network approach
      through a sample of 57 teams, including how to compute, analyze, and visually
      represent team knowledge. RESULTS: Team knowledge network structures (isolation,
      centrality) are associated with outcomes of, respectively, task coordination,
      strategy coordination, and the proportion of team knowledge cliques, all after
      controlling for shared team knowledge. CONCLUSION: Network analysis helps to
      represent, measure, and understand the relationship of team knowledge to outcomes
      of interest to team researchers, members, and managers. Our approach complements
      existing team knowledge measures. APPLICATION: Researchers and managers can apply
      network concepts and measures to help understand where team knowledge is held
      within a team and how this relational structure may influence team coordination,
      cohesion, and performance.

PMID- 24689253
TI  - A network model for human interoperability.
AB  - OBJECTIVE: The objective is to demonstrate how the Human View architecture can be
      used to define and evaluate the human interoperability capabilities of a net
      centric system. Human interoperability strives to understand the types of system
      relationships that affect collaboration across networked environments.
      BACKGROUND: The Human View was developed as an additional system architectural
      viewpoint to focus on the human component of a system by capturing data on human
      roles, tasks, constraints, interactions, and metrics.This framework can be used
      to collect and organize social system parameters to facilitate the way that
      humans interact across organizational boundaries. METHOD: By mapping the Human
      View elements to organizational relationships defined in the domain of network
      theory, a network model of the Human View can be developed.This representation
      can then be aligned with a Layers of Interoperability model for collaborative
      systems.The model extends traditional technical interoperability to include
      organizational aspects important for human interoperability. The resulting
      composite model can be used to evaluate the human interoperability capability of
      network-enabled systems. RESULTS: An interagency response to a crisis situation
      is an example where increased levels of human interoperability can affect the
      effectiveness of the organizational interactions. The existing Human View
      products representing the interagency capabilities were evaluated using the
      network model to demonstrate how the social system variables can be identified
      and evaluated to improve the system design. CONCLUSION: By understanding and
      incorporating human interoperability requirements, the resulting system design
      can more effectively support collaborative tasks across technological
      environments to facilitate timely responses to events.

PMID- 24689254
TI  - Improving social connection through a communities-of-practice-inspired cognitive
      work analysis approach.
AB  - OBJECTIVE: Increasingly, people work in socially networked environments. With
      growing adoption of enterprise social network technologies, supporting effective
      social community is becoming an important factor in organizational success.
      BACKGROUND: Relatively few human factors methods have been applied to social
      connection in communities. Although team methods provide a contribution, they do
      not suit design for communities. Wenger's community of practice concept, combined
      with cognitive work analysis, provided one way of designing for community.
      METHOD: We used a cognitive work analysis approach modified with principles for
      supporting communities of practice to generate a new website design. Over several
      months, the community using the site was studied to examine their degree of
      social connectedness and communication levels. RESULTS: Social network analysis
      and communications analysis, conducted at three different intervals, showed
      increases in connections between people and between people and organizations, as
      well as increased communication following the launch of the new design.
      CONCLUSION: In this work, we suggest that human factors approaches can be
      effective in social environments, when applied considering social community
      principles. APPLICATION: This work has implications for the development of new
      human factors methods as well as the design of interfaces for sociotechnical
      systems that have community building requirements.

PMID- 24689255
TI  - Directional control-response compatibility relationships assessed by physical
      simulation of an underground bolting machine.
AB  - OBJECTIVE: The authors examine the pattern of direction errors made during the
      manipulation of a physical simulation of an underground coal mine bolting machine
      to assess the directional control-response compatibility relationships associated
      with the device and to compare these results to data obtained from a virtual
      simulation of a generic device. BACKGROUND: Directional errors during the manual
      control of underground coal roof bolting equipment are associated with serious
      injuries. Directional control-response relationships have previously been
      examined using a virtual simulation of a generic device; however, the
      applicability of these results to a specific physical device may be questioned.
      METHOD: Forty-eight participants randomly assigned to different directional
      control-response relationships manipulated horizontal or vertical control levers
      to move a simulated bolter arm in three directions (elevation, slew, and sump) as
      well as to cause a light to become illuminated and raise or lower a stabilizing
      jack. Directional errors were recorded during the completion of 240 trials by
      each participant RESULTS: Directional error rates are increased when the control
      and response are in opposite directions or if the direction of the control and
      response are perpendicular.The pattern of direction error rates was consistent
      with experiments obtained from a generic device in a virtual environment.
      CONCLUSION: Error rates are increased by incompatible directional control
      response relationships. APPLICATION: Ensuring that the design of equipment
      controls maintains compatible directional control-response relationships has
      potential to reduce the errors made in high-risk situations, such as underground
      coal mining.

PMID- 24689256
TI  - Cornering law: the difficulty of negotiating corners with an unmanned ground
      vehicle.
AB  - OBJECTIVE: We investigated skill development and workload of pilots driving
      teleoperated unmanned ground vehicles (UGVs) through different apertures and
      viewpoints using the cornering law. BACKGROUND: Due to technological and cost
      restraints, humans are still needed for tasks involving UGVs. Operators of
      teleoperated UGVs are likely to have less situation awareness and thus are more
      prone to getting stuck or damaged when negotiating apertures.To our knowledge,
      the operation of physical UGVs through corners has not been examined. Therefore,
      a better understanding of cornering a teleoperated UGVs is imperative. METHOD: In
      Experiment 1, 20 novice participants repeatedly teleoperated a physical UGV using
      a third-person overhead view through apertures that varied in width. In
      Experiment 2, 18 additional novice participants completed a similar task but used
      a first-person view. RESULTS: Participants' performance increased (i.e., faster
      cornering times and less collisions) over sessions. The cornering law
      successfully modeled the effect of different aperture widths on participant
      performance for both viewing perspectives. CONCLUSION: In this study, we
      successfully modeled human performance of teleoperated UGVs using the cornering
      law. Analogous to Fitts' and steering law, we were able to successfully model and
      predict cornering performance based on a derived index of cornering difficulty.
      APPLICATION: The cornering law could be used to aid in the development of
      prototype user interfaces and also to examine the effects of different
      teleoperation views (first person vs. third person).

PMID- 24689257
TI  - Force-on-Force handgun practice: an intra-individual exploration of stress
      effects, biomarker regulation, and behavioral changes.
AB  - OBJECTIVE: The aim of this study was to explore human factors aspects of reality
      based "force-on-force" (FoF) handgun practice through a within-subjects field
      experiment that assessed subjective stress measurements, biomarker regulation,
      performance outcomes, and behavioral adaptations. BACKGROUND: FoF handgun
      practice is a recent training asset for armed officers whereby dynamic opponents
      may act, react, and even retaliate with specially designed marker ammunition.
      Predesigned scenarios enable trainees to practice in a simulated real-life
      environment. METHOD: A sample of experienced military personnel (N = 20) ran a
      handgun workshop in two conditions: FoF practice and traditional cardboard-target
      practice. Intra-individual assessments included anticipated distress, subjective
      stress, salivary alpha-amylase (sAA), shooting accuracy, and directly observable
      training seriousness. RESULTS: Compared with the standard cardboard practice
      condition, FoF exposure caused significant increases in anticipatory distress,
      subjective stress, and sAA secretion. Furthermore, participants' first encounter
      with FoF practice (vs. cardboard practice) substantially degraded their shooting
      performance and had a significant positive impact on the earnestness with which
      they approached their mission during the workshop. CONCLUSION: FoF practice is an
      effective training tool for armed officers because it simulates a realistic work
      environment by increasing task-specific stress such that it affects important
      outcomes of professional performance and leads to desirable behavioral changes
      during training. APPLICATION: Potential applications of this research include the
      introduction of biomarker assessments in human factors research and the design,
      based on reality-based practice, of effective training procedures for high
      reliability professionals.

PMID- 24689258
TI  - Lane keeping under cognitive load: performance changes and mechanisms.
AB  - OBJECTIVE: A pair of simulated driving experiments studied the effects of
      cognitive load on drivers' lane-keeping performance. BACKGROUND: Cognitive load
      while driving often reduces the variability of lane position. However, there is
      no agreement as to whether this effect should be interpreted as a performance
      loss, consistent with other effects of distraction on driving, or as an anomalous
      performance gain. METHOD: Participants in a high-fidelity driving simulator
      performed a lane-keeping task in lateral wind,with instructions to keep a steady
      lane position. Under high load conditions, participants performed a concurrent
      working memory task with auditory stimuli. Cross-spectral analysis measured the
      relationship between wind force and steering inputs. RESULTS: Cognitive load
      reduced the variability of lane position and increased the coupling between
      steering wheel position and crosswind strength. CONCLUSION: Although cognitive
      load disrupts driver performance in a variety of ways, it produces a performance
      gain in lane keeping.This effect appears to reflect drivers' efforts to protect
      lateral control against the risk of distraction, at the apparent neglect of other
      elements of driving performance. APPLICATION: Results may inform educational
      efforts to help drivers understand the risks of distraction and the inadequacies
      of compensatory driving strategies.

PMID- 24689259
TI  - A focus on patient safety.

PMID- 24689260
TI  - Take action: a culture of safety.
AB  - Nephrology nurses can influence safety outcomes in all areas of nephrology care,
      including but not limited to dialysis access events, dialysis machine events,
      medication events, patient injury events, and staff injury events. Nephrology
      nurses are instrumental in recognizing and mitigating hazards. The Nephrology
      Nursing Scope and Standards of Practice (Gomez, 2011) states that the nephrology
      registered nurse practices in an environmentally safe and healthy manner. One of
      the competencies for the nephrology nurse is: Promotes and monitors the practice
      environment for appropriate infection control practices including consumer
      safety, environmental, and equipment concerns, which impact the healthcare
      consumer. Do you feel safe? Do your patients feel safe? Take action - ensure that
      your organization has a culture of safety; volunteer to be a member of the safety
      committee; review policies and procedures; identify potential hazards.

PMID- 24689261
TI  - A new mindset for quality and safety: the QSEN competencies redefine nurses'
      roles in practice.
AB  - Preventable errors are a major issue in health care. The complexity of health
      care requires interactions among numerous providers for any patient multiple
      times a day. Nurses are the constant presence with patients and have an important
      role in coordinating the contributions of the myriad of caregivers. Nurses are
      also the last line of defense. Increasingly, it is recognized that nurses need to
      be better prepared with quality and safety competencies to have a leading role in
      making our healthcare system safer. This article presents evidence related to
      quality and safety, describes the six core competencies from the Quality and
      Safety Education for Nurses (QSEN) project for integration in nursing practice,
      describes a practice based on inquiry and engagement, and presents a toolkit for
      developing a new mindset based on new quality and safety science.

PMID- 24689262
TI  - Exploring safety and quality in a hemodialysis environment with participatory
      photographic methods: a restorative approach.
AB  - This study used principles and methods of good ecological restoration, including
      participatory photographic research methods, to explore perceptions of safety and
      quality in one hemodialysis unit. Using a list of potential safety and quality
      issues developed during an initial focus group, a practitioner-led photo
      walkabout was conducted to obtain photographs of the patient care unit and
      nurses' stories (photo narration) about safety and quality in their environment.
      Following a process of iterative coding, photos were used to discuss preliminary
      themes in a photo elicitation focus group with four additional unit staff The
      major themes identified related to clutter, infection control, unit design,
      chemicals and air quality, lack of storage space, and health and safety hazards
      (including wet floors, tripping hazards from hoses, moving furniture/chairs). The
      visual methods engaged researchers and unit nurses in rich dialogue about safety
      in this complex environment and provides an ongoing basis for monitoring and
      enhancing safety.

PMID- 24689264
TI  - Error recovery by dialysis technicians.
AB  - Experts are believed to make fewer errors than novices. Researchers in other
      domains have shown that experts not only make less errors, they also detect and
      recover from these errors better than non-experts. To investigate this phenomenon
      among dialysis technicians working in hemodialysis, we evaluated the ability of
      dialysis technicians to detect and recover from healthcare errors. Two clinical
      cases with embedded errors were created by an expert nephrology nurse. Twenty
      four dialysis technician subjects read the cases aloud and then answered a set of
      related questions. Subjects' error detection and recovery responses were scored
      against the clinical cases. We found that there was no significant difference
      between the ability of expert and non-expert dialysis technicians to detect
      errors. However, expert dialysis technicians recovered from significantly more
      healthcare errors than less experienced non-expert dialysis technicians. This has
      implications for training dialysis technicians in better error detection and
      recovery strategies.

PMID- 24689263
TI  - Infection control and bloodstream infection prevention: the perspective of
      patients receiving hemodialysis.
AB  - Patients on hemodialysis, particularly those dialyzed through central lines, are
      at risk of acquiring bloodstream infections. Strategies to prevent bloodstream
      infections in patients on dialysis include educating patients about infection
      prevention, although patients' perspectives on this topic are not known. During
      focus groups conducted to explore these issues, patients reported that education
      on infection prevention should begin early in the process of dialysis, and that
      patients should be actively engaged as partners in infection prevention.

PMID- 24689265
TI  - Hemodialysis catheter outcomes pilot study: no dressing coverage with prescribed
      showering.
AB  - This six-month prospective, multi-site study incorporated no dressing coverage
      over hemodialysis central venous catheter exit sites and compared the outcomes of
      two groups of patients receiving incenter hemodialysis: a shower group and a non
      shower group. Outcomes included exit site infection rates, tunnel infection
      rates, and catheter-related bloodstream infection rates. The study enrolled 40
      patients--31 patients in the shower group and nine patients in the non-shower
      group. The study was initially designed as a randomized controlled study, but
      after a month of enrolling patients, most patients insisted on being in the
      shower group. Results for both groups demonstrated infection rates that were not
      statistically different and were below levels reported in other studies. The
      qualitative satisfaction in ability to shower by patients in this study was an
      additional important finding.

PMID- 24689266
TI  - Shower and no-dressing technique for tunneled central venous hemodialysis
      catheters: a quality improvement initiative.
AB  - Self-care practices and quality-of-life nuances juxtaposed our tunneled
      hemodialysis central venous catheter (CVC) protocols. Despite our advice,
      individuals with CVCs were showering. As a quality improvement initiative, we
      compared the standard CVC dressing practices to the "shower and no-dressing"
      technique. After 1380 catheter months (n = 119) infection rates were 0.31 events
      per 1000 catheter days. The "shower and no-dressing" technique appears to be a
      safe CVC dressing option with improved quality of life, no increase in infection
      rates, and cost-effectiveness.

PMID- 24689267
TI  - Site preparation and needle insertion: impact on patient safety.

PMID- 24689268
TI  - Breaking the safety barrier.

PMID- 24689269
TI  - Alarm fatigue and patient safety.

PMID- 24689270
TI  - The justice behind a just culture.

PMID- 24689271
TI  - Safety issues in home dialysis.

PMID- 24689272
TI  - Pressure ulcer prevention in the patient with spinal cord injury on hemodialysis.

PMID- 24689273
TI  - Patient safety resources on the web.

PMID- 24689274
TI  - Volatile glycosides from the leaves of Morus alba with a potential contribution
      to the complex anti-diabetic activity.
AB  - The leaves and root bark of Morus alba, the white mulberry tree, are well-known
      traditional medicines for the treatment of type II diabetes. Several different
      types of constituents have been suggested to be responsible for the anti-diabetic
      activity of mulberry drugs, such as iminosugars, flavonoids and other phenolic
      compounds, glycopeptides and ecdysteroids. Our group recently suggested that a
      volatile-oil like fraction of the hot water extract of M. alba leaves, containing
      several phenyl-propane derivatives, can increase the glucose consumption of
      adipocytes. Here we report the isolation of three glycosylated volatile
      constituents from mulberry leaves, two megastigmane derivatives along with the
      beta-D-glucoside of eugenol. Furthermore, a commercially available mixture of
      probiotic bacteria was assessed to study the effect of the intestinal flora on
      the megastigmane derivatives. Significant amounts of the aglycons of both
      compounds were liberated, suggesting that these compounds can be metabolized in
      the large intestines and absorbed without the sugar moiety after the consumption
      of a traditional mulberry tea. Based on literature data, both the glycosides and
      their aglycons have a potential contribution to the beneficial effects of
      mulberry leaves in type 2 diabetes.

PMID- 24689275
TI  - A new eudesmane sesquiterpene from Dichrocephala integrifolia.
AB  - A new sesquiterpene, eudesm-11-ene-4alpha,7beta,9beta-triol, was isolated from
      the EtOH extract of aerial parts of Dichrocephala integrifolia. Its structure was
      determined on the basis of spectral analysis of 1D and 2D NMR data.

PMID- 24689277
TI  - Steroidal aglycones from stems of Marsdenia tenacissima that inhibited the
      hedgehog signaling pathway.
AB  - Two novel steroidal aglycones, together with four known ones, were isolated from
      the hydrolysis extract of the CHCl3 soluble extract of the stems of Marsdenia
      tenacissima. Their structures were determined on the basis of chemical evidence
      and extensive spectroscopic methods, including 1D and 2D NMR spectroscopy. These
      compounds displayed inhibition of the Hedgehog signaling pathway in vitro.

PMID- 24689276
TI  - Evaluation of the anti-melanoma activities of sarcophine, (+)-7alpha,8beta
      dihydroxydeepoxysarcophine and sarcophytolide from the Red Sea soft coral
      Sarcophyton glaucum.
AB  - Three natural cembranoids from the Red Sea soft coral Sarcophyton glaucum namely
      sarcophine (1), (+)-7alpha,8beta-dihydroxydeepoxysarcophine (2) and
      sarcophytolide (3) were evaluated for their potential inhibitory effects on
      growth of mouse melanoma B16F10 cells. Compounds (1) and (2) maximally inhibit
      viability of melanoma cells during 48 hr and 72 hr treatment at concentrations
      that show no cytotoxicity on monkey kidney CV-1 cells and also inhibit de novo
      DNA synthesis and PARP activity. Compound (3) produced cytotoxic effects at the
      same concentration range it produces its antitumor effects. These data suggest
      that (1) and (2), but not (3), have potential for further development as
      antitumor agents against melanoma.

PMID- 24689278
TI  - Chemical constituents, and their cytotoxicity, of the rare wood decaying fungus
      Xylaria humosa.
AB  - Samples of Xylaria humosa, a rare species of Xylariaceae, were collected during
      an investigation into the diversity of the fungus in the Phu Khieo Wildlife
      Sanctuary, Thailand. Nine compounds were isolated from the species and their
      structures elucidated by spectroscopic methods. The compounds were ergosterol
      (1), ergosterol peroxide (2), two meroterpenoids, chevalone B and C (3-4),
      together with five indole alkaloids, tryptoquivaline L (5), tryptoquivaline M
      (6), fiscalin A (7), epi-fiscalin A (8) and epi-fiscalin C (9). Compounds 2-9
      exhibited variable cytotoxic activity against KB, NCI-H187 and MCF-7 cell lines.

PMID- 24689279
TI  - Alkaloids from Habranthus tubispathus and H. jamesonii, two amaryllidaceae with
      acetyl- and butyrylcholinesterase inhibition activity.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder associated with memory
      impairment and cognitive deficit. Most of the drugs currently available for the
      treatment of AD are acetylcholinesterase (AChE) inhibitors. Plants of the
      Amaryllidaceae family are known to synthesize alkaloids, which have shown AChE
      inhibitory activity. Habranthus tubispathus and H. jamesonii are two
      Amaryllidaceae that can be found growing wild to the southwest of Buenos Aires in
      Argentina. Acetyl- and butyrylcholinesterase inhibition was observed for the
      extracts obtained from bulbs of H. tubispathus and bulbs and aerial parts of H.
      jamesonii. The strongest cholinesterase inhibition was observed for the alkaloid
      extract obtained from the aerial parts for H. jamesonii (AChE IC50 = 0.7
      microg/mL; BChE IC50 = 6.7 microg/mL). The AChE inhibition observed for H.
      jamesonii could be explained by the presence of galanthamine and sanguinine, two
      potent AChE inhibitors. The levels of lycorine and hippeastidine, moderate AChE
      inhibitors, observed in the bulbs of H. tubispathus could be responsible for the
      significant AChE inhibition observed. The alkaloids present in these
      Amaryllidaceae were identified by means of GC-MS analysis. In the case of H.
      tubispathus, hippeastidine and 3-O-demethylhippeastidine, were isolated and
      completely characterized by 1H and 13C NMR spectroscopy.

PMID- 24689280
TI  - Further characterization of foliar flavonoids in Crossostephium chinense and
      their geographic variation.
AB  - Foliar flavonoids of Crossostephium chinense in Japan and Taiwan were isolated
      and further characterized. Eighteen flavonoid aglycones, luteolin, apigenin,
      hispidulin, chrysoeriol, 5,7,4'-trihydroxy-6,3',5'-trimethoxyflavone, jaceosidin,
      cilsimaritin, quercetin 3-methyl ether, axillarin, chrysosplenol-D, cirsiliol,
      apometzgerin, 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone, luteolin 3',4'
      dimethyl ether, cirsilineol, eupatilin, nepetin and 5,7,3',4'-tetrahydroxy-6,5'
      dimethoxyflavone, were identified by UV, 1H and 13C NMR spectroscopic, LC-MS and
      HPLC comparisons w ith authentic samples. The compounds existed on the leaf
      surface. Four flavonoid glycosides, quercetin 3,7-di-O-glucoside, quercetin 3-O
      rutinoside, luteolin 7-O-glucoside and apigenin 7-O-rutinoside, were also
      isolated as the intracellular flavonoids. It was shown by HPLC survey that
      variation of the species' flavonoids occurs among the collection sites.

PMID- 24689281
TI  - Hawaiian propolis: comparative analysis and botanical origin.
AB  - Propolis is a resinous mixture of substances collected and processed from various
      botanical sources by honeybees (Apis mellifera). We recently obtained Hawaiian
      propolis, the study of which, to our knowledge, has not been reported. The
      purpose of this study was to analyze the composition of Hawaiian propolis and to
      identify its botanical origin. A comparative analysis of Hawaiian and Okinawan
      propolis and of the glandular trichomes on Macaranga tanarius fruit (the
      botanical origin of Okinawan propolis) was performed using reversed-phase high
      performance liquid chromatography coupled with high resolution-electrospray mass
      spectrometry. Hawaiian propolis contained nine prenylflavonoids that were also
      isolated from Okinawan propolis. In conclusion, we suggest that the botanical
      origin of Hawaiian propolis is M. tanarius, the same as that of Okinawan
      propolis.

PMID- 24689282
TI  - Nutritional and functional properties of aqueous and hydroalcoholic extracts from
      Argentinean propolis.
AB  - Bee propolis is a natural product extensively used as an ingredient in functional
      foods in amounts that may confer health benefits. The aim of this study was to
      investigate the nutritional and functional properties (antioxidant activity) of
      aqueous and ethanolic extracts of propolis samples from Santiago del Estero
      province, northern Argentina. All propolis extracts contained macronutrients
      (glucose, fructose, sucrose and proteins), micronutrients (Na, K, Ca, P and Mg)
      and trace elements (Fe). Spectrophotometric, TLC and HPLC-DAD analyses showed the
      presence of several phenolic, flavonoid and non-flavonoid compounds, but in all
      cases the flavonoids prevailed. The PCA of polyphenolic content provided a clear
      separation of propolis in Group 1 (SE1, 2, 3, 4 and 7) and Group 2 (SE5 and 6)
      associated with phenolic compound content and collection regions. Two compounds,
      pinocembrin and chrysin, which could be used as chemical markers of Santiago del
      Estero propolis, were identified in all samples. Propolis samples extracted with
      water presented better radical scavenging ability than ethanolic extracts,
      independent of the antioxidant method (scavenging activity of ABTS*+, DPPH*, HO*
      and O2(-)* and beta-carotene bleaching test). Such results correlated closely
      with the levels of total phenols and flavonoids in samples. The results justify
      the use of Argentine propolis as a functional dietary supplement.

PMID- 24689283
TI  - Anti-trypanosomal phenolic derivatives from Baccharis uncinella.
AB  - Bioassay-guided fractionation of the EtOH extract of the aerial parts of
      Baccharis uncinella C. DC. (Asteraceae) led to identification of two cinnamic
      acid derivatives (caffeic and ferulic acids), two flavones (hispidulin and
      pectolinaringenin) and a mixture of three chlorogenic acids (3,4-, 3,5- and 4,5-O
      dicaffeoylquinic acids), which displayed in vitro anti-trypanosomal activity.
      Pectolinaringenin, hispidulin and caffeic acid showed activity against
      trypomastigotes of Trypanosoma cruzi, exhibiting 50% inhibitory concentration
      (IC50) values of 52, 81 and 56 microg/mL, respectively, while the chlorogenic
      acid mixture showed an IC50 value of 61 microg/mL. The flavonoids and cinnamic
      acid derivatives were evaluated for cytotoxicity against NCTC cells resulting in
      a 50% cytotoxic concentration (CC50) ranging from 33.82 to 129.1 microg/mL while
      the chlorogenic acids did not display cytotoxicity (CC50 >150 microg/mL). This is
      the first report of anti-trypanosomal activity of compounds from B. uncinella.

PMID- 24689284
TI  - Polyphenols in representative Teucrium species in the flora of R. Macedonia:
      LC/DAD/ESI-MS(n) profile and content.
AB  - In the present work, the polyphenolic profile and content of four Teucrium
      species (T. chamaedrys L., T. montanum L., T. polium L., T. scordium L.) from the
      Macedonian flora were examined. A LC/DAD/ESI-MS(n) chromatographic method was
      optimized and 31 phenolic compounds were identified, quantified and classified
      into four groups: hydroxycinnamic acid derivatives (2), phenylethanoid glycosides
      (12), flavonoid glycosides (11) and flavonoid aglycones (6). The total phenolic
      content (mg/g dry herb) ranged from 28.2 (T. montanum), 30.9 (T. scordium), 35.1
      (T. polium) to 52.1 (T. chamaedrys). Phenylethanoid glycosides were the
      predominant group ofpolyphenols in the studied samples contributing 60% of the
      total phenolic content for T. polium and T. scordium and around 90% for T.
      montanum and T. chamaedrys. The systematic analysis for identification and
      quantification of all present phenolic compounds contributes to the chemotaxonomy
      of the investigated Teucrium species and to the valorization based on their
      phenolic profiles and content.

PMID- 24689285
TI  - In vitro inhibitory effects of Limonium contortirameum and L. virgatum extracts
      from sardinia on alpha-amylase, alpha-glucosidase and pancreatic lipase.
AB  - Pancreatic triacylglycerol lipase (PL), alpha-amylase and alpha-glucosidase are
      interesting pharmacological targets for the management of dyslipidemia,
      atherosclerosis, and obesity-diabetes. Limonium spp (Plumbaginaceae) are endemic
      to Sardinia, Italy. Comparable with acarbose, aqueous extracts (AE) of L.
      contortirameum and L. virgatum, and their phytoconstituent gallic acid
      concentration gradients (mg/mL) were identified as in vitro potent (p<0.001, n=3)
      and efficacious dual inhibitors of alpha-amylase and alpha-glucosidase with
      respective IC50 (mg/mL) values of 0.6 +/- 0.1, 1.2 +/- 0.1 and 0.15 +/- 0.02.
      Equivalent to orlistat (PL IC50 of 0.114 +/- 0.004 microg/mL), L. contortirameum,
      L. virgatum AE and their phytoprinciple gallic acid inhibited PL substantially
      (p<0.001, n=3) in a dose-dependent manner in vitro with PL- IC50 (microg/mL) of
      920.4 +/- 105.2, 593.1 +/- 56.8 and 8.4 +/- 0.9, respectively. LC-MS analysis of
      extracts revealed the presence of several phenolic compounds in their aglycon and
      glycoside forms. These are catechins, flavones, epigallocatechins and flavonols.
      Flavonoid- and polyphenol-rich L contortirameum and L. virgatum, modulating
      gastrointestinal carbohydrate and lipid digestion and absorption, may be
      advocated as candidates for obesity-diabetes prevention and phytotherapy.

PMID- 24689286
TI  - Search for skin-whitening agent from Prunus plants and the molecular targets in
      melanogenesis pathway of active compounds.
AB  - In our research program for discovering novel skin-whitening materials, screening
      of extracts from flowers of some Prunus species was performed using an anti
      tyrosinase assay. Among the tested plants, the flowers of P. persica showed the
      most potent inhibitory activity. In addition, P. persica also showed suppression
      of melanogenesis in B16 rat melanoma cells. The active principles of tyrosinase
      inhibition and suppression of melanogenesis were revealed to be an afzelin (3-O
      alpha-L-rhamnosylkaempferol) and a flavanone, naringenin. The mechanism of the
      anti-melanogenesis effect of these two compounds was disclosed, for the first
      time, as the suppression of the expression of tyrosinase protein, which was
      controlled by the inhibition of phosphorylation of p38 MAPK. These findings show
      that these compounds could be candidates for the novel molecular target for a
      skin-whitening agent.

PMID- 24689287
TI  - In silico prediction of tyrosinase and adenylyl cyclase inhibitors from natural
      compounds.
AB  - Although many herbal medicines are effective in the treatment of
      hyperpigmentation, the potency of different constituents remains unknown. In this
      work, more than 20,000 herbal ingredients from 453 herbs were docked into the
      crystal structures of adenylyl cyclase and a human homology tyrosinase model
      using Surflex-Dock. These two enzymes are responsible for melanin production and
      inhibition of them may attain a skin-whitening effect superior to currently
      available agents. The essential drug properties for topical formulation of the
      herbal ingredients, including skin permeability, sensitization, irritation,
      corrosive and carcinogenic properties were predicted by Dermwin, Skin
      Sensitization Alerts (SSA), Skin Irritation Corrosion Rules Estimation Tool
      (SICRET) and Benigni/Bossa rulebase module of Toxtree. Moreover, similarity
      ensemble and pharmacophore mapping approaches were used to forecast other
      potential targets for these herbal compounds by the software, SEArch and
      PharmMapper. Overall, this study predicted seven compounds to have advanced drug
      like properties over the well-known effective tyrosinase inhibitors, arbutin and
      kojic acid. These seven compounds have the highest potential for further in vitro
      and in vivo investigation with the aim of developing safe and high-efficacy skin
      whitening agents.

PMID- 24689288
TI  - Molecular docking and reaction kinetic studies of chrysin binding to serum
      albumin.
AB  - The binding properties of chrysin with serum albumin (SA) were investigated under
      physiological conditions by calorimetry, circular dichroism (CD) spectroscopy,
      and molecular modeling. Based on the thermodynamic data, molar reaction enthalpy,
      reaction order (n) and the rate constant (k) were calculated. The results of CD
      spectroscopy showed that chrysin could bind to SA and the conformation of SA did
      not have any high-ordered structural change. Computational mapping revealed
      chrysin binding to the subdomain IB in SA. The chrysin-serum albumin complex was
      stabilized by hydrophobic force and hydrogen bonding and the reaction was a
      spontaneous process.

PMID- 24689289
TI  - Anthocyanins from the flowers of Nagai line of Japanese garden Iris (Iris
      ensata).
AB  - Six anthocyanins were isolated from the flowers of the Nagai line of Iris ensata
      Thunb. They were identified as petunidin and malvidin 3-O-beta-[(4"'-Z-p
      coumaroyl-alpha-rhamnopyranosyl)-(1-->6)-beta-glucopyranoside]-5-O-beta
      glucopyranosides (1 and 3) and their E-forms (2 and 4), and petunidin and
      malvidin 3-O-rutinoside-5-O-glucosides (5 and 6). Though the E-form of petunidin
      3-O-[(4"'-p-coumaroylrhamnosyl)-(1-->6)-glucoside]-5-O-glucoside has been
      reported, its Z-form was found for the first time. The presence of Z- and E-forms
      of malvidin 3-O-[(4'''-p-coumaroylrhamnosyl)-(1-->6)-glucoside]-5-O-glucoside is
      also reported for the first time. Fifty-one cultivars of Nagai line and their
      wild form (I. ensata var. spontanea) were divided into four anthocyanin patterns,
      i.e. 1) the presence of 1-4, 2) the presence of 2 and 4, 3) the presence of 5 and
      6, and 4) no anthocyanin.

PMID- 24689290
TI  - New chromone and triglyceride from Cucumis melo seeds.
AB  - Re-investigation of the MeOH extract of the seeds of Cucumis melo L. var.
      reticulatus (Cucurbitaceae) led to the isolation of a new chromone derivative
      (5,7- dihydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]chromone (5) and a
      triglyceride (1,3-di-(6Z,9Z)-docosa-6,9-dienoyl-2-(6Z) hexacos-6-enoylglycerol
      (1), together with three known compounds; alpha-spinasterol (2), stigmasta
      7,22,25-trien-3-ol (3), and D:B-friedoolean-5-ene-3-beta-ol (4), are reported
      from this species for the first time. Their structures were determined by
      extensive 1D (1H, 13C, and DEPT) and 2D (1H-1H COSY, HMQC, and HMBC) NMR and mass
      spectral measurements. Compound 5 displayed significant cytotoxic activity
      against L5178Y cells, with an ED50 of 5 microM. The MeOH extract and 5 showed
      antioxidant activity using the DPPH assay.

PMID- 24689291
TI  - Five new acylphloroglucinol glycosides from the leaves of Eucalyptus robusta.
AB  - Five new acylphloroglucinol glycosides, robustasides A-E (1-5), together with a
      known one (6), were isolated from the leaves of Eucalyptus robusta. The
      structures were elucidated on the basis of extensive spectroscopic and
      spectrometric analysis and chemical evidence. The absolute configuration of 1 was
      further determined by quantum chemical CD calculation.

PMID- 24689292
TI  - Usnic acid and triacylglycerides production by the cultured lichen mycobiont of
      Ramalina celastri.
AB  - A strain of the lichen mycobiont of Ramalina celastri, isolated from ascospores,
      was cultured axenically on two solid media containing high amounts of the carbon
      source: sucrose in MY10 and mannitol in BMRM. Usnic acid, the major cortical
      lichen metabolite, was produced by the colonies grown on MY10, with a very high
      yield (7.9%) in comparison with that in the lichen thallus. Mycelia grown on BMRM
      did not produce the lichen secondary metabolite and rendered triacylglycerides
      (8.5%) instead. Analysis by GC-MS of the fatty acid methyl esters revealed the
      presence of oleic, palmitic and stearic acids as the main triacylglyceride
      constituents. The present results highlight the impact of the culture conditions
      on the lichen mycobiont secondary metabolism and confirm that MY10 is a useful
      medium to obtain usnic acid from mycobionts in the laboratory.

PMID- 24689293
TI  - A new lignan glycoside from Chamaecyparis obtusa var. breviramea f. crippsii.
AB  - A new lignan glycoside, (-)-(8S, 8'R)-thujastandin-4-O-beta-D-glucopyranoside
      (1), together with fourteen known lignanoids (2-15) and one coumarin (16) were
      isolated from the branches and leaves of Chamaecyparis obtusa var. breviramea f.
      crippsii. Their structures were elucidated by extensive spectroscopic and
      spectrometric analysis. Compound 16 exhibited cytotoxicity against A549, BGC-823
      and Hela cell lines with IC50 values of 25.9, 20.9 and 18.5 microM, respectively.

PMID- 24689294
TI  - Synthesis of 2-acetyl-1,4-dimethoxynaphthalene, a potential intermediate for
      disubstituted naphtho[2,3,c]pyran-5,10-dione.
AB  - 2-Acetyl-1-hydroxynaphthalene was converted into the title compound in three
      steps (bromination, substitution and methylation). 1-Methoxynaphthalene on
      bromination, substitution and acetylation, respectively, also yielded the target
      compound.

PMID- 24689295
TI  - Anthraquinone and naphthoquinone derivatives from the roots of Coptosapelta
      flavescens.
AB  - Investigation of the acetone and methanol extracts of the roots of Coptosapelta
      flavescens using various chromatographic techniques led to the isolation of four
      anthraquinones (1 and 3-5) and one naphthoquinone (2). 1,4-Dimethoxy-2
      methylanthraquinone (1) and 2-amino-3-methoxycarbonyl-1,4-naphthoquinone (2) are
      reported as natural compounds for the first time. This is the first report on the
      phytochemistry and biological activity of compounds from C. flavescens.

PMID- 24689297
TI  - Biological studies of turmeric oil, part 3: anti-inflammatory and analgesic
      properties of turmeric oil and fish oil in comparison with aspirin.
AB  - Turmeric and fish oil have been gaining interest as food supplements because of
      their beneficial properties. Turmeric oil contains sesquiterpenes and fish oil
      has eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possessing anti
      inflammatory activity. The present study is to evaluate and compare the anti
      inflammatory and analgesic properties of these two natural food products with
      aspirin as a standard. The percent inhibition as a measure of paw edema for
      turmeric oil and fish oil at 100 mg/kg was 76% and 31%, respectively, while the
      percent inhibition by the combination of the two at 100 mg/kg was 62%, which was
      the same as that of aspirin at the same dose. The inhibitory activity of fish oil
      at 50 mg/kg was 86% and with an increase in dose the activity decreased. The
      analgesic activity measured by the tail flick method showed optimum activities
      for turmeric oil and fish oil at 60 and 90 minutes, respectively, whereas the
      combination of the two decreased the analgesic activity. Thus the two common food
      ingredients, oils from turmeric and fish, have desirable biochemical properties
      to develop further their use as food and medicine.

PMID- 24689298
TI  - Cyclic dipeptides produced by marine sponge-associated bacteria as quorum sensing
      signals.
AB  - Four bacterial strains belonging to the genera Vibrio, Pseudoalteromonas and
      Photobacterium were isolated from the marine sponges Dysidea avara and Geodia
      cynodium. A Bacillus strain was isolated from Ircinia variabilis. A screening of
      molecules involved in quorum sensing (QS) was carried out by TLC-overlay and a
      new "plate T-streak" test. To analyze quorum quenching (QQ), a plate T-streak was
      performed with Chromobacterium violaceum. Strains of Vibrio isolated from both
      marine sponges and a strain of Photobacterium isolated from G. cynodium,
      activated QS bioreporters. A strain of Pseudoalteromonas isolated from D. avara
      showed QQ activity. Finally, it is reported that cyclic dipeptides isolated from
      strains of Vibrio sp. and Bacillus sp. (isolated from D. avara and I. variabilis,
      respectively) were involved in the QS mechanism. The simultaneous presence of
      bacteria that showed contrasting responses in bioassays for QS signal molecule
      synthesis in marine sponges could add an interesting dimension to the signalling
      interactions which may be happening in sponges.

PMID- 24689296
TI  - Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus
      faecalis and Enterococcus faecium active dimeric isobutyrylphloroglucinol from
      Ivesia gordonii.
AB  - Bioassay-guided fractionation of the chloroform soluble fraction of stem, leaf,
      and flower extracts of the American plant Ivesia gordonii led to the isolation of
      a new dimeric acylphloroglucinol, 3,3'-diisobutyryl-2,6'-dimethoxy-4,6,2',4'
      tetrahydroxy-5,5'dimethyldiphenyl methane (1), to which we have assigned the
      trivial name ofivesinol (1), together with a known monomeric acylphloroglucinol,
      1,5-dihydroxy-2-(2'-methylpropionyl)-3-methoxy-6-methylbenzene (2). The
      structures of the isolated compounds were characterized using 1D- and 2D- NMR
      spectroscopy, including COSY, HMQC, HMBC, and ROESYexperiments, as well as mass
      spectrometry. Ivesinol (1) showed potent activity against Staphylococcus aureus
      (SA) and methicillin-resistant S. aureus (MRSA) with IC50/MIC/MBC values of
      0.10/1.25/>20 microg/mL and 0.05/0.31/>20 microg/mL, respectively (vs.
      IC50/MIC/MBC 0.13/0.5/1.0 microg/mL and 0.13/0.5/1.0 microg/mL of ciprofloxacin),
      while the corresponding monomer 2 was found to be less active. Compound 1 also
      demonstrated strong activity against vancomycin-resistant Enterococcus faecium
      (VRE) with IC50/MlC/MBC values of 0.22/1.25/>20 microg/mL, whereas the reference
      standard ciprofloxacin was found to be inactive against this strain. In addition,
      compound 2 showed moderate activity against two species of Candida and
      Cryptococcus neoformans, while 1 was inactive against these fungi. In order to
      evaluate the influence of the acyl group(s) in phloroglucinol (3) as a ligand,
      the mono- (4) and diacetylphloroglucinol (5) were prepared from 3, and evaluated
      for their in vitro SA, MRSA, and VRE activities; 2,4-diacetylphloroglucinol (5)
      showed potent activity, like 1, against SA, MRSA, and VRE (ATCC 700221) with
      IC50/MIC values of 0.3/2.5, 0.23/2.5, and 0.86/2.5 microg/mL, respectively, while
      4 was inactive.

PMID- 24689299
TI  - Isolation of the tetrapeptide apicidins G, H and I from the fungus Fusarium
      semitectum.
AB  - This study reports the isolation and characterization of three new tetrapeptides,
      apicidins G (1), H (2) and I (3), along with the known apicidin (4), apicidin A
      (5), apicidin C (6), diketopiperazine 7, equisetin (8) and 7-hydroxy-2-(2
      hydroxypropyl)-5-methylchromone (9). The structures of the new compounds were
      deduced by 2D NMR spectroscopic and MSdata.

PMID- 24689300
TI  - The co-identity of lipiarmycin A3 and tiacumicin B.
AB  - The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes
      deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was
      unambiguously demonstrated through a number of experimental means. Spectroscopic
      analyses performed on both the antibiotics themselves and on their derivatives
      showed no difference between the two series of compounds. Moreover, unambiguous
      confirmation of the postulated identity of the two compounds was achieved by
      chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4
      triol triacetate whose relative configuration was assigned by comparison with the
      authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical
      synthesis.

PMID- 24689301
TI  - PSY-1, a Taxus chinensis var. mairei extract, inhibits cancer cell metastasis by
      interfering with MMPs.
AB  - Cancer is the most common disease worldwide, with death often occurring as a
      result of metastasis. Thus, interfering with metastasis has been regarded as a
      promising strategy to improve the current cancer treatments. However, exploration
      and development of novel anti-metastatic agents remains a major challenge. Recent
      evidence indicated that a polysaccharide isolated from Taxus yunnanensis
      suppressed tumor cells proliferation. With the objective of seeking bioactive
      extracts, we had previously isolated, purified and characterized a complex, water
      soluble polysaccharides, PSY-1, from the leaves of Taxus chinensis var. mairei,
      and identified its anti-neoplastic effects. In this study, we focused on the
      effects of PSY-1 on cancer metastasis and its mechanism(s). The results
      illustrated that PSY-1 effectively suppressed the migration and invasion ability
      of the melanoma cancer cell line B16-F10, caused down-regulation of MMP-2 and MMP
      9, and that the NF-kappaB pathway was involved in the anti-metastatic effects
      imposed by PSY-1.

PMID- 24689302
TI  - Antimicrobial activity of endophytic fungi isolated from Swietenia macrophylla
      leaves.
AB  - The endophytic fungi isolated from leaves of Swietenia macrophylla of different
      ages were examined for antimicrobial activity. The agar plug diffusion assay was
      used for primary screening, followed by the disc diffusion method. A total of 461
      filamentous endophytic fungi were isolated and cultured to examine their
      antimicrobial properties. In the primary screen, 315 isolates (68.3%) exhibited
      activity against at least one of the test pathogenic microorganisms. The
      percentage of isolates exhibiting antimicrobial activity increased with leaf age.
      Endophytic fungal assemblages, as well as those isolates exhibiting antimicrobial
      properties appeared to increase with leaf age. The main antimicrobial compounds
      were produced extracellularly by the endophytic fungi. The results suggest that
      healthy leaves at older stages of growth can be a potential source for the
      isolation of endophytic fungi with antimicrobial properties.

PMID- 24689303
TI  - Aroma profile of star anise and the structure-odor relationship of anethole.
AB  - Star anise is an important fragrance material that has a characteristic anise
      like odor. Although the main component of star anise is (E)-anethole, which
      accounts for over 90% of the constituents, the odor of (E)-anethole is different
      from that of the material itself. Here, we examined the aroma profile of star
      anise. GC-MS analysis of star anise extracts showed that it contains many
      compounds with structures similar to (E)-anethole. Our results indicate that (E)
      anethole is the key compound in the odor of star anise, but structurally similar
      compounds play an important role in creating its odor. We examined the structure
      odor relationship of (E)-anethole, focusing on the methoxy and 1-propenyl
      substituents. Altering the 1-propenyl group changed the odors of all the anethole
      derivatives. Replacing the methoxy group with a hydrogen atom created compounds
      with similar fatty odors. This shows that the methoxy group is important for the
      characteristic odor of anethole. We synthesized anethole derivatives where the
      methoxy group was replaced with a methyl group. In both methoxy- and methyl
      substituted anethole derivatives, altering the 1-propenyl group changed the odors
      of the derivatives. Therefore, the methoxy and methyl benzene moieties are
      important structural features for the odor of star anise. The structural
      characteristics of anethole are closely related to its odor expression.

PMID- 24689304
TI  - The essential oil of Populus balsamifera buds: its chemical composition and
      cytotoxic activity.
AB  - The chemical composition of Populus balsamifera essential oils obtained from
      spring buds, fall buds, and young leaves were determined by GC and GC-MS
      analyses. The major constituent, (+)-alpha-bisabolol, a rare sesquiterpene, was
      isolated from spring oil using reverse-phase preparative HPLC. The cytotoxic
      activity of balsam poplar oils and isolated (+)-alpha-bisabolol was assessed in
      vitro against human lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1)
      cell lines. Essential oils were cytotoxic with IC50 ranging from 35 to 50
      microg/mL. (+)-alpha-Bisabolol exhibited pronounced activity (IC50 14 microg/mL)
      against both cancer cell lines. It also exhibited interesting cytotoxic activity
      (IC50 23 microg/mL) against human glioma (U251), higher than the one observed for
      (-)-alpha-bisabolol (IC50 34 microg/mL), which is known for its apoptosis
      inducing effect against glioma cells.

PMID- 24689305
TI  - Comparative chemical study and cytotoxic activity of Uvariodendron angustifolium
      essential oils from Benin.
AB  - This study aimed to compare the chemical composition of volatile extracts
      obtained by hydrodistillation of leaves, stems, bark and roots of Uvariodendron
      angustifolium (Engl. & Diels) R. E. Fries. The essential oils, obtained with
      yields between 0.12 and 0.66%, were analyzed by GC/FID and GC/MS. A great
      variability in the chemical composition was observed depending on the plant part
      treated. The essential oils obtained from leaves and stems contained mainly neral
      (29.7-30.5%) and geranial (42.9-47.3%), while methyl eugenol was the major
      component of the volatile extracts from bark (68.3%) and roots (85.3%).
      Interesting cytotoxic properties of these essential oils on human breast cancer
      cells MCF-7 were demonstrated.

PMID- 24689306
TI  - Composition of essential oil from Tagetes minuta and its cytotoxic, antioxidant
      and antimicrobial activities.
AB  - The essential oil from the leaves of Tagetes minuta L., growing wild in Yemen,
      was obtained by hydrodistillation and analyzed by gas chromatography-mass
      spectrometry. A total of 28 compounds were identified representing 74.2% of total
      oil composition. Major components of the essential oil were (Z)-ocimenone
      (15.9%), (E)-ocimenone (34.8%), (Z)-beta-ocimene (8.3%), limonene (2.3%), (Z)
      tagetone (1.8%), dihydrotagetone (1.4%) and an unidentified dimethylvinylketone
      derivative (20.6%). The oil showed moderate cytotoxic activity against MCF-7
      breast tumor cells, with an IC50 of 54.7 +/- 6.2 microg/mL. In the DPPH radical
      scavenging assay, T. minuta oil showed potent antiradical activity with an IC50
      value of 36 microg/mL. Antimicrobial activity was also investigated on several
      microorganisms, and the essential oil exhibited high activity against methicillin
      resistant Staphylococcus aureus (MRSA) with an inhibition zone of 23 mm. It also
      exhibited remarkable antifungal activity against Candida albicans with an
      inhibition zone of 26 mm.

PMID- 24689307
TI  - Chemical composition of the essential oil of Croton bonplandianus from India.
AB  - The essential oil obtained from the aerial parts of Croton bonplandianus Baill.
      was analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry
      (GC/MS). A total of 37 compounds have been identified, representing 96.2% of the
      total oil. The main constituents were identified as beta-caryophyllene (16.7%),
      germacrene D (14.7%), borneol (8.3%), Z-beta-damascenone (6.(%), isobornyl
      acetate (6.2%), alpha-humulene (6.1%), germacrene A (5.2%) and caryophyllene
      oxide (4.5%). The oil was rich in sesquiterpene hydrocarbons (60.1%).

PMID- 24689308
TI  - Chemical composition of Angelica pancicii essential oil determined by liquid and
      headspace GC-MS techniques.
AB  - The essential oil of the Balkan endemic species, Angelica pancicii, obtained by
      hydrodistillation, was analyzed by GC and GC-MS, applying the liquid injection
      mode. These results were compared with the chemical composition of volatiles
      achieved by the "headspace" injection mode, followed by GC and GC-MS (HS-GC-MS).
      A total of 40 compounds were identified in the essential oil (98.8% of the total
      oil) and 44 by HS-GC-MS (99.8% of the total oil). The most abundant class of
      compounds in both cases was monoterpenoids, which formed 92.7% of the essential
      oil (97.7% by HS-GC-MS) of total identified compounds. The major components in
      both cases were beta-phellandrene (54.9% and 60.1%, respectively), alpha-pinene
      (14.5% and 20.1%, respectively) and alpha-phellandrene (4.5% and 4.3%,
      respectively).

PMID- 24689309
TI  - Chemical description and essential oil yield variability of different accessions
      of Salvia lavandulifolia.
AB  - The amount and chemical composition of essential oils are crucial for the
      modulation of the flavor, scent and therapeutic properties of aromatic and
      medicinal plants. The aim of this study was to evaluate the effects of phenology
      and weather conditions on the essential oil yield obtained from the aerial parts
      of Salvia lavandulifolia Vahl. Besides, we tried to carry out an approach to the
      chemical composition at the time of full bloom. Essential oil production of
      several accessions was monitored throughout the whole phenological cycle, both,
      at the original location growing wild and at the experimental plot as cultivated
      plants. Local pedoclimatic conditions seem to be crucial for the plant essential
      oil production. Our results showed high conditioning rates from both yearly
      climatic conditions and developmental stage of the plants. Maximum yield
      production was reported at the full seed maturation stage (average 1.74%) and
      after a slight dry period (average 2.16%). Phytochemical differences were
      maintained when plants were forced to grow under common pedoclimatic conditions.
      Thereby, essential oil analysis showed some populations formed by clearly
      distinct individuals while others had more homogenous plants. Compounds such
      alpha-pinene, beta-pinene + myrcene, limonene, 1,8-cineol, camphor and beta
      caryophyllene were the main compounds of the essential oils of S. lavandulifolia.

PMID- 24689310
TI  - Antimicrobial constituents and synergism effect of the essential oils from
      Cymbopogon citratus and Alpinia galanga.
AB  - From the fresh leaf sheathes of lemongrass (Cymbopogon citratus) and rhizomes of
      galanga (Alpinia galanga) light yellow and colorless oils, respectively, were
      obtained by hydrodistillation and microwave assisted extraction (MAE) in yields
      of 0.24% and 0.03%, and 0.11% and trace (w/w), respectively. By GC/MS analysis,
      five major constituents were identified in lemongrass oil, E-citral, Z-citral,
      beta-myrcene, selina-6-en-4-ol, and cis-ocimene, and five in galanga oil, 1,8
      cineole, phenol 4-(2-propenyl)-acetate, dl-limonene, alpha-pinene, and a
      terpineol. Three major components of the combined lemongrass and galanga oils
      (ratio 7:3, 1:1, 3:7) were 1,8-cineole (46.3%, 31.5%, 19.3%), E-citral (12.8%,
      22.7%, 32.8%) and Z-citral (8.5%, 15.2%, 21.6%). The MICs of lemongrass and
      galanga oils were: against Staphylococcus aureus 0.5% and 4%, v/v, against
      Pseudomonas aeruginosa 40% and >40%,v/v, against Streptococcus bovis 0.25% and
      0.5%, v/v, and against Candida albicans 0.25% and 0.5%, v/v. Citral (from
      lemongrass oil) gave greater potentiation than 1,8-cineole (from galanga oil).
      The combination profiles of galanga oil with lemongrass oil (volume ratios 3:7,
      1:1, and 7:3) were tested against the four pathogenic microorganisms. Synergistic
      activity was best noted for only one ratio (volume ratio 3:7) as the sigmafic< 1
      against all tested microorganisms. The present investigation provides evidenc
      that the utilization of two essential oils in combination should be assessed for
      synergistic antimicrobial activity in order to reduce their minimum effective
      dose.

PMID- 24689311
TI  - In vitro antibacterial activity of Libanotis montana essential oil in combination
      with conventional antibiotics.
AB  - The chemical composition and antibacterial activity were examined of Libanotis
      montana Crantz subsp. leiocarpa (Heuff.) Soo. (Apiaceae) essential oil. Gas
      chromatography and gas chromatography/mass spectrometry were used to analyze the
      chemical composition of the oil. The antibacterial activity was investigated by
      the broth microdilution method against thirteen bacterial strains. The
      interactions of the essential oil and three standard antibiotics: tetracycline,
      streptomycin and chloramphenicol toward five selected strains were evaluated
      using the microdilution checkerboard assay in combination with chemometric
      methods: principal components analysis and hierarchical cluster analysis.
      Sesquiterpene hydrocarbons were the most abundant compound class in the oil
      (67.2%), with beta-elemene (40.4%) as the major compound. The essential oil
      exhibited slight antibacterial activity against the tested bacterial strains in
      vitro, but the combinations L. montana oil-chloramphenicol and L. montana oil
      tetracycline exhibited mostly either synergistic or additive interactions. These
      combinations reduced the minimum effective dose of the antibiotics and,
      consequently, minimized their adverse side effects. In contrast, the association
      of L. montana essential oil and streptomycin was characterized by strong
      antagonistic interactions against Escherichia coli ATCC 25922. In the PCA and HCA
      analyses, streptomycin stood out and formed a separate group.

PMID- 24689312
TI  - Modernization of Ayurveda: a brief overview of Indian initiatives.
AB  - Ayurveda has been the main guiding force in drug discovery from traditional
      medicine. In concept, this system is rooted in folk or ethnomedicine and in
      practice it shows further refinement and development in accordance with local
      traditions. Isolation of active principles from crude drugs, their
      pharmacological evaluation, therapeutic proving and clinical application resulted
      in the genesis of modem or so called allopathic medicine. To keep the opportunity
      alive for further development in traditional as well as modem medicines, it is
      necessary to have an uninterrupted connection with ethnomedicine. Since the
      practice of ethnomedicine is based on the age-long indigenous knowledge which has
      been orally transmitted through generations and sustained in traditions there is
      an urgent need to document such knowledge. The ongoing strategies adopted in
      India to document the precious traditional knowledge and conserve medicinal
      plants are discussed in this communication. India with her rich plant wealth and
      traditional knowledge about the medicinal use of plants has tremendous scope to
      provide leadership in ensuring human health and longevity.

PMID- 24689313
TI  - Documenting new HIV/AIDS research and interventions in sub-Saharan Africa.

PMID- 24689314
TI  - Improving health services for adolescents living with HIV in sub-Saharan Africa:
      a multi-country assessment.
AB  - In sub-Saharan Africa (SSA), the aging of HIV-positive pediatric cohorts and
      growing numbers of adolescents on treatment, coupled with high HIV incidence in
      this age group, means the number of adolescents living with HIV (ALHIV) will
      continue to grow. The clinical, psychological, social, and reproductive health
      needs of ALHIV remain poorly understood and efforts to mobilize and advocate for
      their treatment, care, and support have been inadequate. A multi-country
      assessment of the needs of ALHIV in SSA found that comprehensive, adolescent
      friendly services that champion peer support and collaboration between health
      care organizations can foster successful transitions into adulthood for ALHIV.

PMID- 24689315
TI  - Why are virgin adolescents worried about contracting HIV/AIDS? Evidence from four
      sub-Saharan African countries.
AB  - Whether well founded or not, perceptions of one's own HIV risk have been shown by
      health behavior models to be an important factor in determining individuals'
      sexual behavior. Although empirical studies on the determinants of HIV risk
      perception exist, only a few have focused on adolescents who are not yet sexually
      active. Using data from nationally-representative surveys of adolescents, we
      assess the factors associated with HIV risk perception among sexually inactive
      adolescents in four sub-Saharan African countries at different stages of the
      HIV/AIDS epidemic (Burkina Faso, Ghana, Malawi and Uganda). The results show that
      there is no single influence on adolescents' HIV risk perception, but rather a
      range of individual, environmental and community factors such as schooling,
      knowledge about HIV, regional HIV prevalence and adolescents' social networks.
      These results can help better calibrate programs and policies addressing sexual
      and reproductive health issues among adolescents, a group that is
      disproportionately affected by new HIV infections.

PMID- 24689316
TI  - Drivers of young people's attitudes towards HIV/AIDS stigma and discrimination:
      evidence from Ghana.
AB  - Using data from the 2008 Ghana Demographic and Health Survey, this paper examines
      the drivers of young people's attitudes towards HIV/AIDS stigma and
      discrimination in Ghana. Descriptive statistics and binary logistic regression
      were used to examine these drivers. The odds of low stigma and discrimination
      attitudes increased with higher education: thus, males [OR = 11.04; 95% CI = 4.59
      26.54] and females [OR = 5.12; 95% CI = 2.41-11.28] with higher education were
      significantly more likely to express positive attitudes towards people living
      HIV. Controlling for beliefs, myths and knowledge about causes of HIV, the
      influence of education on HIV-related stigma among males and females reduces
      considerably but the odds remain statistically significant. Beliefs, myths and
      knowledge of HIV causes/prevention had varying significant effects on stigma.
      Ethnic, regional and religious differences also emerged in the results. The
      findings suggest that people with better and accurate knowledge about HIV,
      particularly its transmission have lower tendencies of showing HIV-related stigma
      and discrimination. Both formal and informal education on HIV should be pursued
      rigorously as part of the larger efforts at reducing HIV.

PMID- 24689317
TI  - Knowledge, attitudes and practices about HIV testing and counselling among
      adolescent girls in some selected secondary schools in Malawi.
AB  - The major objective of this study was to determine knowledge, attitudes and
      practices about HIV testing services and the uptake of this service amongst girls
      aged 15-19 in selected secondary schools in Malawi. A questionnaire was
      administered to 457 students and 18 focus group discussions and 45 in-depth
      interviews were conducted. The study found that almost every student knew about
      HTC but uptake was low as only about a third of the students reported having been
      tested. The uptake of this service also increased with age. Most of those tested
      wanted to know their sero-status. Others were tested because it was a
      requirement. Sixty nine per cent of the girls who did not go for the HIV test was
      mainly because either they were not sexually active or they felt they were not at
      risk. During FGDs some students did not test because they feared their parents
      would think they were sexually promiscuous. This study demonstrates the need for
      intensive campaigns among adolescent girls and their parents to create awareness
      about the importance of HIV testing as this is an entry point for all HIV and
      AIDS services.

PMID- 24689318
TI  - A review of HIV/AIDS awareness and knowledge of preventive methods in Ghana.
AB  - This paper reviews HIV/AIDS awareness, knowledge and preventive methods in Ghana
      over the past two decades drawing heavily on the 2003 and 2008 Ghana Demographic
      and Health Surveys (GDHS). The review reveals that there is almost a universal
      awareness of HIV/AIDS in Ghana although there are still some deficiencies in
      comprehensive knowledge of the epidemic. Nevertheless, there seem to be some
      gender differences in the level of awareness since men have more knowledge on
      HIV/AIDS including its prevention than women. Besides, it is revealed that
      knowledge of preventive measures lagged behind awareness of the epidemic. In
      addition, male respondents between 15 and 24 years are more aware of the
      preventive measures than their female counterparts. Against the backdrop that
      women are more affected by the epidemic than men, there is the need to intensify
      the knowledge and preventive methods of HIV/AIDS especially among the women in
      their reproductive age.

PMID- 24689319
TI  - Estimating the number of male sex workers with the capture-recapture technique in
      Nigeria.
AB  - Estimating the size of populations most affected by HIV such as men who have sex
      with men (MSM) though crucial for structuring responses to the epidemic presents
      significant challenges, especially in a developing society. Using capture
      recapture methodology, the size of MSM-SW in Nigeria was estimated in three major
      cities (Lagos, Kano and Port Harcourt) between July and December 2009. Following
      interviews with key informants, locations and times when MSM-SW were available to
      male clients were mapped and designated as "hotspots". Counts were conducted on
      two consecutive weekends. Population estimates were computed using a standardized
      Lincoln formula. Fifty-six hotspots were identified in Kano, 38 in Lagos and 42
      in Port Harcourt. On a given weekend night, Port Harcourt had the largest
      estimated population of MSM sex workers, 723 (95% CI: 594-892) followed by Lagos
      state with 620 (95%CI: 517-724) and Kano state with 353 (95%CI: 332-373). This
      study documents a large population of MSM-SW in 3 Nigerian cities where higher
      HIV prevalence among MSM compared to the general population has been documented.
      Research and programming are needed to better understand and address the health
      vulnerabilities that MSM-SW and their clients face.

PMID- 24689320
TI  - Transactional sex, condom and lubricant use among men who have sex with men in
      Lagos State, Nigeria.
AB  - Men who have unprotected sex with men may also have unprotected sex with women
      and thus serve as an epidemiological bridge for HIV to the general population.
      This cross sectional descriptive study assessed condom and lubricant use and
      practice of transactional sex among men who have sex with men (MSM) in Lagos
      state. Simple random sampling was used to select three community centres and
      snowball sampling technique was used to recruit 321 respondents. Almost half
      (50.9%) had received payment for sex while 45.4% had paid for sex in the past.
      Consistent condom use was practiced by 40.5% of respondents during the last 10
      sexual encounters, 85.6% used lubricants mostly with condom, products used were
      KY jelly, body cream, saliva and Vaseline. There is need for behavioural change
      to reduce risky practices which predisposes this group of MSM to HIV and sexually
      transmitted infections.

PMID- 24689321
TI  - Sexual and reproductive health in HIV serodiscordant couples.
AB  - Serodiscordant couples are a significant source of new HIV infection in sub
      Sahara Africa. The prevention of HIV transmission to the uninfected partner
      should be an integral part of their health care. Serodiscordant couples desire
      pregnancy, treatment for infertility, effective family planning services, sexual
      health screening, and so on. This paper reviews the sexual and reproductive
      health needs of heterosexual serodiscordant couples, based on current evidence
      and recommendations.

PMID- 24689322
TI  - Intrapartum management for prevention of mother-to-child transmission of HIV in
      resource-limited settings: a review of the literature.
AB  - Prevention of mother-to-child transmission (PMTCT) of HIV guidelines in resource
      limited settings focus on antenatal and postnatal management. In this review of
      the literature, we present findings from select studies, highlight best
      practices, and present evidence-based guidelines for intrapartum PMTCT management
      that are applicable to resource-limited settings. We discuss the roles of
      intrapartum HIV testing, intrapartum antiretroviral medications, mode of delivery
      in settings with and without HIV RNA testing, other delivery practices, and
      infant care in the immediate postnatal period. With the advent of Option B+,
      which recommends all HIV-infected pregnant women commence lifelong combination
      antiretroviral therapy (ART), the potential impact for intrapartum interventions
      will be greatest for those women who recently have seroconverted and those with
      unknown HIV status. Research on intrapartum PMTCT interventions should focus on
      these populations.

PMID- 24689323
TI  - A qualitative analysis of the barriers and facilitators to receiving care in a
      prevention of mother-to-child program in Nkhoma, Malawi.
AB  - Prior to 2011, uptake of PMTCT in Malawi remained low despite increased access to
      antiretrovirals. We sought to understand barriers to PMTCT in rural Malawi.
      Twenty-two HIV-infected pregnant and postpartum women in PMTCT programs were
      interviewed in Nkhoma, Malawi, between April-May 2010. All women were staged by
      WHO criteria or CD4 count as ineligible for three-drug treatment by Malawi's HIV
      Guidelines at the time. The median age was 26 years (range 22-39) and 77% were
      married. Barriers to accessing PMTCT care included transportation to clinic,
      stigma in the community leading to avoidance of HIV disclosure, food insecurity,
      and providers' attitudes towards HIV-infected pregnant women. Given Malawi's
      transition to Option B+ for PMTCT in which women are initiated on antiretroviral
      therapy (ART) during pregnancy and continued for life, strategies to improve
      access and retention will need to address barriers and incorporate facilitators
      that motivate and retain women in HIV care.

PMID- 24689324
TI  - Scaling up prevention of mother to child transmission of HIV infection to primary
      health facilities in Nigeria: findings from two primary health centres in
      Northwest Nigeria.
AB  - Nigeria is scaling up prevention of mother-to-child transmission (PMTCT) of HIV
      interventions to primary health care centres (PHCs). This retrospective study of
      PMTCT was at two PHCs in Northwest Nigeria with the main outcome measure being
      HIV infection rate of exposed infants at 6 weeks of life. Of 10,289 women who had
      antenatal HIV test, 74 had positive results. This gave a prevalence of 0.7%. The
      uptake of antenatal (99.8%) and intrapartum (97.3%) tests was high at both
      centres. 30% of HIV infected mothers and 25% of exposed infants were lost to
      follow-up (LFU). Most women (85.7%) had highly active antiretroviral therapy
      (HAART) and vaginal delivery (98%). Perinatal mortality rate was 66/1000 births
      and 95.3% of exposed infants had negative HIV-DNA polymerase reaction test at 6
      weeks of life. Despite a high LFU, a new vista has been opened to attaining a
      zero infection rate.

PMID- 24689325
TI  - Declining rate of infection with maternal human immunodeficiency virus at
      delivery units in north-central Nigeria.
AB  - HIV testing during labour and delivery provides a critical opportunity for
      administering appropriate interventions to prevent mother-to-child-transmission
      (PMTCT). We studied current HIV rates and infection trend among women tested
      during delivery following scale-up of PMTCT and antiretroviral therapy (ART)
      programs in Jos, north central Nigeria. Between March 2010 and January 2012,
      provider-initiated HIV testing and counselling was offered in early labour. Women
      were recruited from a government tertiary health centre, a faith-based hospital,
      and a private health centre. Those who previously tested HIV negative during
      antenatal care (ANC) and those who presented at the labour ward with unknown HIV
      status were tested. A total of 944 subjects (727 re-tested for HIV infection and
      217 with unknown HIV status) were enrolled and tested during labour. The HIV
      incidence and sero-conversion rates during pregnancy among women who repeated HIV
      testing at delivery was 1.7 per 100 person-years of observation (pyo) and 0.6%
      (4/727), respectively, while the rate among those who tested for the first time
      in labour was 1.8% (4/217). Women who accessed ANC were older and had achieved a
      higher educational status than those who did not access ANC. A 3- to 5-fold
      decline in HIV incidence and prevalence rates was detected among women tested at
      delivery when compared to data from a report in 2004. It is not certain whether
      the decline in maternal HIV infection is due to the major state-wide scale-up of
      PMTCT and HIV treatment programs. A broader and purposefully designed evaluation
      study would be required to verify observed occurrence.

PMID- 24689326
TI  - Methodological issues in HIV-related social research in Nigeria.
AB  - This paper is about methodological issues in a community-wide study in Nigeria on
      an infectious disease, namely HIV/AIDS. The study was designed to ascertain the
      risk factors that contribute to the spread of HIV/AIDS and how that can be
      tackled in order to bring about behavioural change. The research team believed at
      the onset that a study on the interplay between HIV/AIDS and sensitive issues
      like sexual mores and sexuality requires much more than a straightjacket social
      science method, such as simply doing a cross-section study and/or using interview
      schedule. This paper reviews the essence of cross-disciplinary approach; team
      building; as well as the use of a non-participatory observational approach in
      data collection. It also shows why ample consideration was given to ethical
      issues which are often glossed over in social research in developing countries.
      The lessons from the study underscore the methodological imperatives in social
      research that focus on sensitive issues in largely non-literate context like
      Nigeria. Although there are formidable challenges in community-based studies in
      largely non-literate societies, nevertheless they could easily be surmounted if
      there are ample time and resources to navigate the various sticking points.

PMID- 24689327
TI  - The relationship between female genital mutilation and HIV transmission in sub
      Saharan Africa.
AB  - Female genital mutilation (FGM) is an age-old practice that has since been linked
      with many health problems. This review aims to highlight some of the
      controversies trailing the relationship between FGM and HIV transmission in sub
      Saharan Africa. A literature search was conducted on the subject matter. This was
      done using articles published in English while limiting the geographical coverage
      to sub-Saharan Africa. Three themes were noted. These themes include: Direct
      causal link between FGM and HIV transmission; indirect causal link between FGM
      and HIV transmission and a negative or no association between FGM and HIV
      transmission. While many of the arguments are within scientific reasoning, the
      researches supporting the views seem to lack the necessary objectivity. This
      study underscored the need for a more objective lens in viewing and conducting
      research on the relationship between FGM and HIV transmission in sub-Saharan
      Africa.

PMID- 24689328
TI  - Sexual dysfunction among HIV patients: three case reports and review of
      literature.
AB  - Global efforts in addressing the HIV/AIDS epidemic have focused on preventing new
      infections, reduction of viral loads through treatment and care and support for
      the patients. Hardly any attention has been given to their quality of life in
      particular sexual health and functioning. There is a growing body of literature
      indicating high prevalence of sexual problems amongst HIV-infected individuals,
      whose mechanisms remain unclear. This may affect individuals' quality of life,
      interpersonal relationships and HIV treatment. The sub-Saharan Africa (SSA)
      region is the epicentre of the HIV epidemic, majority of the patients being young
      (< 30 years old) and in long-term heterosexual relationships. With increased life
      expectancy due to expanded access to HAART, the prevalence and potential impact
      of sexual dysfunction are certain to be significant. There is urgent need for
      appropriate research on sexual experiences and functioning amongst HIV patients
      in SSA and appropriate interventions to address them. Current efforts to link
      HIV/AIDS and sexual and reproductive health and rights (SRHR) and proposals to
      make SRH services integrated and comprehensive provide are a good starting point.
      However SRHR policies, strategic plans and programmes should be reviewed to
      ensure inclusion of sexual health.

PMID- 24689329
TI  - Assessment of community mobilization and home-based HIV counselling and testing
      offered by health facilities in rural Uganda.
AB  - Home-based HIV counselling and testing (HBHCT) and community mobilization have
      been proven to be effective in increasing the number of people linked to HIV care
      and treatment. An assessment was conducted in 18 health facilities in Uganda to
      evaluate the availability and extent of home based testing services and community
      mobilization activities in underserved communities. The performance of the health
      facilities was assessed using a checklist with indicators of HBHCT and community
      mobilization. While most of the health facilities (72.2%) had active community
      mobilization, only 12.2% had HBHCT services and this might have affected
      universal access to HIV prevention, care and treatment. The health facilities did
      not accompany their intensive community mobilization activities with HBHCT yet
      this provided the ideal entry point and opportunity to improve linkage to HIV
      treatment and care.

PMID- 24689330
TI  - Psychological disorders among human immunodeficiency virus-infected adults in
      southern Nigeria.
AB  - Persons living with HIV/AIDS (PLWHA) have been reported to be more at risk of
      developing mental illness than the general population. A cross sectional study
      was carried out to evaluate psychological symptoms of PLWHA. A total of one
      hundred and thirteen persons living with HIV/AIDS (M = 43, F = 70) with an age
      range of 21-65 years X = 38.00 +/- 9.68 participated in the study. Paranoid
      ideation, Depression, Neuroticism, Interpersonal sensitivity and Anxiety were the
      most common psychopathologic symptoms. Women reported a higher proportion of
      psychopathology compared to men on all subscales. There was no significant
      statistical difference between the age groups on all symptoms evaluated. Single
      PLWHA in this study had a higher tendency towards psychopathology compared to the
      married or widowed. The psychopathological proportion of symptoms reported by
      PLWHA in this study calls for concern. Mental health screening and psychological
      intervention thus remains imperative in the care of PLWHA in Nigeria.

PMID- 24689331
TI  - Announcing open science badges and reaching for the sky.

PMID- 24689332
TI  - Religious bias among religiously conscious black christians in the United States.
AB  - Research with White participants has demonstrated religious intergroup bias;
      however, religious identity may be different for Black Americans. Only
      religiously conscious Black Christians demonstrated a preference for Christian
      targets over Muslim and Atheist targets. Future research should consider what
      factors result in a person becoming conscious of other's religion.

PMID- 24689334
TI  - Clarifying the relationship between ostracism and relational devaluation.
AB  - We examine how three perspectives on relational devaluation relate to needs
      threat following ostracism. In two experiments with 179 first-year psychology
      students, distress was greatest when participants were ostracized without any
      prior throws, and distress decreased linearly with increasing prior inclusion. In
      Experiment 3, using 76 first-year psychology students, we manipulated
      expectations of exclusion and found expectations predicted distress following
      ostracism, suggesting ostracism's distress can be influenced by norm-based
      expectations of inclusion, and that progressive relational devaluation is not a
      necessary condition for ostracism's distress.

PMID- 24689333
TI  - Excluded by laughter: laughing until it hurts someone else.
AB  - Can laughter cause social pain? Given the host of ways exclusion is communicated,
      we examined if exclusive laughter could produce the aversive consequences
      accordant with social exclusion. Using a validated recall paradigm, participants
      recounted a time of exclusive or inclusive laughter or a typical Wednesday
      (control condition). Participants recalling exclusive laughter felt more
      ostracized, increased social pain. thwarted basic needs, worsened mood, reduced
      relational evaluation, and increased temptations to aggress compared to inclusive
      laughter or a typical Wednesday; there were generally no significant differences
      between the inclusive laughter and a typical Wednesday. Participants recalling
      exclusive laughter also felt more verbally and emotionally bullied, demonstrating
      empirically, for one of the first times, a link between social exclusion and
      bullying.

PMID- 24689335
TI  - Resentment of paternalism as system change sentiment: hostile sexism toward men
      and actual behavior in the 2008 U.S. presidential election.
AB  - Taking inspiration from Glick and colleagues (2004), this study tested the idea
      that resentment of paternalism (which is part of the hostile sexism toward men
      construct) might approximate desire for system change by correlating this
      variable with actual behavior associated with system change in a single culture.
      Specifically, voting behavior in the 2008 U.S. presidential election was
      predicted from political party affiliation, measures of hostile and benevolent
      sexism toward both women and men, and egalitarian racial attitudes using a U.S.
      college student sample. Results indicated that the only significant predictors of
      voting behavior were political party affiliation, resentment of paternalism, and
      egalitarian racial attitudes. Higher levels of resentment of paternalism were in
      fact associated with voting for the ticket that represented system change-holding
      the other predictors constant.

PMID- 24689336
TI  - Accuracy, consensus, in-group bias, and cultural frame shifting in the context of
      national character stereotypes.
AB  - We examined Finns' and bilingual Swedish-Finns' stereotypes regarding personality
      differences between Finns and Swedish-Finns and compared them with their
      respective self-ratings. Stereotype ratings by both groups converged on depicting
      Swedish-Finns as having a more desirable personality. In-group bias also
      influenced stereotypes. Contrary to predictions based on the Stereotype Content
      Model, out-group stereotypes were not compensatory. Consistent with the kernel of
      truth hypothesis of national stereotypes, Swedish-Finns' aggregate self-ratings
      resembled their stereotype of personality differences between the two groups, and
      their personality self-ratings were more desirable than Finns' self-ratings.
      Tentatively suggesting the occurrence of cultural frame shifting, the resemblance
      between Swedish-Finns' self-ratings and their stereotype of Swedish-Finns was,
      although only marginally statistically significantly, somewhat stronger when the
      self-ratings were provided in Swedish.

PMID- 24689337
TI  - An investigation of the associations between contingent self-worth and
      aspirations among Iranian university students.
AB  - This study investigated the novel associations between intrinsic and extrinsic
      aspirations and internal and external domains of contingent self-worth among a
      sample of 502 Iranian university students. We found a meaningful pattern showing
      that intrinsic aspirations were positively associated with internal domains,
      whereas extrinsic aspirations were positively associated with external domains.
      Our survey data also suggested that the factor structure of the Aspiration Index,
      as well as the factor structure of the Contingencies of Self-Worth Scale in our
      Iranian sample were consistent with factor structures of foreign samples.
      Finally, the types of aspirations and domains of contingencies of self-worth
      meaningfully predicted variables related to well-being, confirming previous
      research. We discuss the nature of the associations between the aspirations and
      the domains of contingent self-worth.

PMID- 24689338
TI  - No place to hide: when shame causes proselfs to cooperate.
AB  - Shame is considered a social emotion with action tendencies that elicit socially
      beneficial behavior. Yet, unlike other social emotions, prior experimental
      studies do not indicate that incidental shame boosts prosocial behavior. Based on
      the affect as information theory, we hypothesize that incidental feelings of
      shame can increase cooperation, but only for self-interested individuals, and
      only in a context where shame is relevant with regards to its action tendency. To
      test this hypothesis, cooperation levels are compared between a simultaneous
      prisoner's dilemma (where "defect" may result from multiple motives) and a
      sequential prisoner's dilemma (where "second player defect" is the result of
      intentional greediness). As hypothesized, shame positively affected proselfs in a
      sequential prisoner's dilemma. Hence ashamed proselfs become inclined to
      cooperate when they believe they have no way to hide their greediness, and not
      necessarily because they want to make up for earlier wrong-doing.

PMID- 24689339
TI  - Using Facebook to deliver a social norm intervention to reduce problem drinking
      at university.
AB  - INTRODUCTION AND AIMS: University students usually overestimate peer alcohol use,
      resulting in them 'drinking up' to perceived norms. Social norms theory suggests
      correcting these inflated perceptions can reduce alcohol consumption. Recent
      findings by the current authors show portraying oneself as 'a drinker' is
      considered by many students to be a socially desirable component of their
      Facebook identity, perpetuating an online culture that normalises binge drinking.
      However, social networking sites have yet to be utilised in social norms
      interventions. DESIGN AND METHODS: Actual and perceived descriptive and
      injunctive drinking norms were collected from 244 university students. Ninety
      five students screened positive for hazardous drinking and were randomly
      allocated to a control group or intervention group that received social norms
      feedback via personalised Facebook private messages over three sessions. RESULTS:
      At 1 month post-intervention, the quantity and frequency of alcohol consumed by
      intervention group during the previous month had significantly reduced compared
      with baseline and controls. Reductions were maintained 3 months post
      intervention. Intervention group perceived drinking norms were significantly more
      accurate post-intervention. DISCUSSION AND CONCLUSIONS: This is the first study
      to test the feasibility of using Facebook to deliver social norms interventions.
      Correcting misperceptions of peer drinking norms resulted in clinically
      significant reductions in alcohol use. Facebook has many advantages over
      traditional social norms delivery, providing an innovative method for tackling
      problem drinking at university. These results have implications for the use of
      Facebook to deliver positive messages about safe alcohol use to students, which
      may counter the negative messages regarding alcohol normally seen on Facebook.

PMID- 24689340
TI  - Myeloma stem cell concepts, heterogeneity and plasticity of multiple myeloma.

PMID- 24689341
TI  - Efficient light bending with isotropic metamaterial Huygens' surfaces.
AB  - Metamaterial Huygens' surfaces manipulate electromagnetic wavefronts without
      reflection. A broadband Huygens' surface that efficiently refracts normally
      incident light at the telecommunication wavelength of 1.5 MUm is reported. The
      electric and magnetic responses of the surface are independently controlled by
      cascading three patterned, metallic sheets with a subwavelength overall thickness
      of 430 nm. The peak efficiency of the device is significantly enhanced by
      reducing the polarization and reflection losses that are inherent to earlier
      single-layer designs. 

PMID- 24689342
TI  - High TMEM45A expression is correlated to epidermal keratinization.
AB  - TMEM45A (DERP7, DNAPTP4 or FLJ10134) gene, belonging to the TMEM family encoding
      predicted transmembrane proteins, is highly expressed in epidermal keratinocytes.
      To investigate the potential involvement of TMEM45A during the differentiation
      and keratinization processes, its expression has been characterized in normal
      human keratinocytes and the protein subcellular localization has been studied in
      this cell type, both in vitro and in vivo. TMEM45A expression is upregulated with
      differentiation, either induced by cultured keratinocyte confluence or enhanced
      Ca(2+) concentration in medium. In vivo, TMEM45A mRNA and protein are mostly
      found in the granular layer of the epidermis. TMEM45A expression is linked to
      keratinization, as accumulation of the protein is detected in native and
      reconstructed epidermis as well as in thymic Hassal bodies, but not in non
      keratinized stratified epithelia. At the subcellular level, co-detection with ER
      and Golgi markers reveals that TM protein 45A is associated with the Golgi
      apparatus and more specifically with the trans-Golgi/trans-Golgi network in vitro
      and in granular layer in vivo. The protein is neither related to lysosomes nor
      transported within corneodesmosin-containing lamellar bodies. These data
      demonstrate a strong correlation between TMEM45A expression and epidermal
      keratinization, indicating the relevance of this gene in this process. 

PMID- 24689343
TI  - Commentary: tenofovir is superior to entecavir in HBeAg-positive chronic
      hepatitis B patients.

PMID- 24689344
TI  - Commentary: tenofovir is superior to entecavir in HBeAg-positive chronic
      hepatitis B patients--authors' reply.

PMID- 24689345
TI  - Commentary: independent risk factors for recurrent neoplasia after endoscopic
      resection of early gastric cancer.

PMID- 24689346
TI  - Commentary: independent risk factors for recurrent neoplasia after endoscopic
      resection of early gastric cancer--authors' reply.

PMID- 24689347
TI  - Letter: apoptosis and hepatic fibrosis in chronic hepatitis B.

PMID- 24689348
TI  - Letter: apoptosis and hepatic fibrosis in chronic hepatitis B--authors' reply.

PMID- 24689349
TI  - Letter: gender-associated cell-free microRNA profiles in non-alcoholic fatty
      liver disease.

PMID- 24689350
TI  - Letter: gender-associated cell-free microRNA profiles in non-alcoholic fatty
      liver disease--authors' reply.

PMID- 24689351
TI  - Letter: probiotics vs. lactulose for minimal hepatic encephalopathy therapy.

PMID- 24689352
TI  - Letter: probiotics vs. lactulose for minimal hepatic encephalopathy therapy-
      authors' reply.

PMID- 24689353
TI  - Letter: low risk of colorectal cancer in a Greek cohort of inflammatory bowel
      disease patients.

PMID- 24689354
TI  - Characterization of biodegradable polyurethane nanoparticles and thermally
      induced self-assembly in water dispersion.
AB  - Waterborne polyurethanes (PU) with different compositions of biodegradable
      oligodiols as the soft segment were synthesized as nanoparticles (NPs) in this
      study. Using dynamic light scattering (DLS), multiangle light scattering (MALS),
      transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS),
      we demonstrated that these NPs were compact spheres with different shape factors.
      The temperature-dependent swelling of the PU NPs in water was distinct. In
      particular, PU NPs with 80 mol % polycaprolactone (PCL) diol and 20 mol % poly(L
      lactide) (PLLA) diol as the soft segment had significant swelling (~450%) at 37 
      degrees C. This was accompanied by a sol-gel transition observed in about 2 min
      for the NP dispersion. The thermally induced swelling and self-assembly of these
      NPs were associated with the secondary force (mainly hydrogen bonding) and degree
      of crystallinity, which depended on the soft segment compositions. The thermo
      responsiveness of the PU NPs with mixed biodegradable oligodiols may be employed
      to design smart biodegradable carriers for delivery of cells or drugs near body
      temperature.

PMID- 24689355
TI  - Topochemistry of environmentally friendly pretreatments to enhance enzymatic
      hydrolysis of sugar cane bagasse to fermentable sugar.
AB  - In this work, dilute alkaline and alkaline peroxide pretreatments were conducted
      in comparison with hydrotropic pretreatment to improve the delignification of
      bagasse prior to enzymatic hydrolysis. The surface chemical composition of
      bagasse after pretreatments was investigated by X-ray photoelectron spectroscopy
      (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The surface
      distribution of lignin and extractives on the bagasse fiber was significantly
      changed by dilute alkaline, alkaline peroxide, and hydrotropic pretreatments.
      Hydrotropic pretreatment typically showed, other than the decrease of surface
      coverage by lignin and extractives, dramatic removal of xylan, thereby leading to
      more cellulose exposed on the fiber surface after pretreatment. Fiber morphology
      after pretreatments was more favorable for enzyme hydrolysis as well. However,
      the hydrotropic treatment had clear advantages because the enzymatic hydrolysis
      yields of glucan and xylan of pretreated bagasse were 83.9 and 14.3%,
      respectively. 

PMID- 24689356
TI  - Molecular iodine promoted divergent synthesis of benzimidazoles, benzothiazoles,
      and 2-benzyl-3-phenyl-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazines.
AB  - An unprecedented formation of a new class of 2-benzyl-3-phenyl-3,4-dihydro-2H
      benzo[e][1,2,4]thiadiazines has been discovered during the course of
      benzimidazole and benzothiazole synthesis, through the molecular iodine-mediated
      oxidative cyclization with a new C-N and S-N bond formation at ambient
      temperature. 

PMID- 24689357
TI  - A prospective, observational study of the volumizing effect of open-label
      aesthetic use of Juvederm(r) VOLUMA(r) with Lidocaine in mid-face area.
AB  - INTRODUCTION: Juvederm(r) VOLUMA(r) with Lidocaine is a hyaluronic acid (HA)
      based injectable gel that is used to restore the volume of the face. This study
      was designed to assess the real-world effectiveness of this HA gel over 21 days
      when used for mid-face augmentation in normal, healthy subjects desiring
      aesthetic improvement. MATERIALS AND METHODS: This prospective, observational,
      single-arm, open-label post-marketing study enrolled 115 healthy subjects, from
      five European centers. The primary objective was to evaluate subject-reported
      satisfaction and experience of the treatment across a range of doses of
      Juvederm(r) VOLUMA(r) with Lidocaine (1 ml/2 ml/combination), immediately after
      injection and 21 days post-treatment. RESULTS: Subject satisfaction questionnaire
      (SSQ) scores of Delighted or Happy were given by 95.6% of subjects immediately
      after injection, and by 93.7% of subjects at Day 21. Overall, subject and
      investigator satisfaction with cosmetic effect and smoothness was very positive.
      Pain was minimal; most subjects experienced only minor degrees of discomfort, and
      this was mainly related to the procedure itself. CONCLUSIONS: Juvederm(r)
      VOLUMA(r) with Lidocaine was well accepted by both subjects and investigators,
      associated with high levels of satisfaction, was considered smooth and easy to
      use, and was well tolerated when used for the treatment of mid-face area volume
      enhancement.

PMID- 24689358
TI  - Structure and dynamics of single hydrophobic/ionic heteropolymers at the vapor
      liquid interface of water.
AB  - We focus on the conformational stability, structure, and dynamics of
      hydrophobic/charged homopolymers and heteropolymers at the vapor-liquid interface
      of water using extensive molecular dynamics simulations. Hydrophobic polymers
      collapse into globular structures in bulk water but unfold and sample a broad
      range of conformations at the vapor-liquid interface of water. We show that
      adding a pair of charges to a hydrophobic polymer at the interface can
      dramatically change its conformations, stabilizing hairpinlike structures, with
      molecular details depending on the location of the charged pair in the sequence.
      The translational dynamics of homopolymers and heteropolymers are also different,
      whereas the homopolymers skate on the interface with low drag, the tendency of
      charged groups to remain hydrated pulls the heteropolymers toward the liquid side
      of the interface, thus pinning them, increasing drag, and slowing the
      translational dynamics. The conformational dynamics of heteropolymers are also
      slower than that of the homopolymer and depend on the location of the charged
      groups in the sequence. Conformational dynamics are most restricted for the end
      charged heteropolymer and speed up as the charge pair is moved toward the center
      of the sequence. We rationalize these trends using the fundamental understanding
      of the effects of the interface on primitive pair-level interactions between two
      hydrophobic groups and between oppositely charged ions in its vicinity. 

PMID- 24689359
TI  - Use of an online community to provide support to caregivers of people with
      dementia.
AB  - One challenge faced by many family members caring for persons with dementia is
      lack of information about how to take care of others and themselves. This is
      especially important for persons from ethnic minority groups, because
      linguistically and culturally appropriate information is often not available. In
      response to these needs, we developed a web site for Spanish-speaking caregivers.
      Cuidatecuidador.com provides bilingual information on dementia and caregiver
      issues. Content was developed and then evaluated by caregivers residing in 3
      countries. Findings suggest trends that exposure to information may be related to
      a higher sense of mastery and a reduction of depressive symptomatology. 

PMID- 24689360
TI  - The risk factors for hospital re-admission in medical patients in Singapore.
AB  - Unplanned hospital re-admissions are common, expensive and often unpreventable in
      the community. The study aimed to identify risk factors associated with unplanned
      hospital re-admission in Singapore. In a cross-sectional survey, 1509 patients
      admitted to the medical wards of a large acute hospital in Singapore during 2010
      were recruited (78.8% response rate), data being collected using a structured
      questionnaire based on the Andersen behavioural model underlying healthcare use.
      The dependent variable was re-admission within 28 days, with independent
      variables in the four areas of predisposing characteristics, needs, enabling
      resources and health behaviour. Hierarchical logistic regression was used to
      evaluate the risk factors associated with unplanned hospital re-admission. There
      were 222 inpatients re-admitted (14.7%) within 28 days and the final model showed
      that patients who were unemployed (OR = 1.5; 95% CI = 1.1-2.1) and had chronic
      obstructive pulmonary disease (OR = 2.0; 95% CI = 1.1-3.7) with abnormal
      respiratory patterns (OR = 1.6; 95% CI = 1.1-2.2) were more likely to be re
      admitted. Less likely to be re-admitted were patients doing regular daily
      activities (OR = 0.7; 95% CI = 0.5-0.9), those assisted by a social worker (OR =
      0.3; 95% CI = 0.2-0.6), those referred to other health professionals when sick
      (OR = 0.6; 95% CI = 0.4-0.7) and those who had received health education
      programmes before discharge in the previous admission (OR = 0.7; 95% CI = 0.4
      0.9). Unplanned re-admissions are a concern to healthcare providers because this
      suggests that patients are discharged with unresolved problems that reflect
      ineffective care in hospital. This study provides evidence to prompt more
      effective discharge educational care programmes that incorporate patients'
      enabling and need outcomes, thereby reducing re-admission rates. Community-based
      healthcare should play an important role in reducing patients' re-admission
      rates. 

PMID- 24689361
TI  - Can frequent precipitation moderate the impact of drought on peatmoss carbon
      uptake in northern peatlands?
AB  - Northern peatlands represent a large global carbon store that can potentially be
      destabilized by summer water table drawdown. Precipitation can moderate the
      negative impacts of water table drawdown by rewetting peatmoss (Sphagnum spp.),
      the ecosystem's key species. Yet, the frequency of such rewetting required for it
      to be effective remains unknown. We experimentally assessed the importance of
      precipitation frequency for Sphagnum water supply and carbon uptake during a
      stepwise decrease in water tables in a growth chamber. CO2 exchange and the water
      balance were measured for intact cores of three peatmoss species (Sphagnum majus,
      Sphagnum balticum and Sphagnum fuscum) representative of three hydrologically
      distinct peatland microhabitats (hollow, lawn and hummock) and expected to differ
      in their water table-precipitation relationships. Precipitation contributed
      significantly to peatmoss water supply when the water table was deep,
      demonstrating the importance of precipitation during drought. The ability to
      exploit transient resources was species-specific; S. fuscum carbon uptake
      increased linearly with precipitation frequency for deep water tables, whereas
      carbon uptake by S. balticum and S. majus was depressed at intermediate
      precipitation frequencies. Our results highlight an important role for
      precipitation in carbon uptake by peatmosses. Yet, the potential to moderate the
      impact of drought is species-specific and dependent on the temporal distribution
      of precipitation.

PMID- 24689362
TI  - Malpractic in nursing: The experience in Turkey.
AB  - This cross-sectional study was conducted with 562 nurses to find out nurses'
      opinions and practices concerning medical errors and to measure their tendency to
      make medical mistakes. Data were collected using a questionnaire and Tendency for
      Medical Errors Scale and evaluated using Student's t and one-way ANOVA tests. The
      average total score of the participating nurses was 4.4 +/- 0.3. It was observed
      that 36.1% nurses made medical errors, and all of those nurses making mistakes
      have stated that they have made medication errors. It was found that nurses with
      higher education and working in the intensive care unit had a lower tendency,
      whereas those working in children's hospital had a higher tendency to make
      medical mistakes (P < 0.05). It might be recommended that the working conditions
      of nurses be improved, and nurses in general and particularly, those working with
      pediatric patients be given regular training to prevent drug administration
      errors. 

PMID- 24689363
TI  - Current evidence supporting fertility and pregnancy among young survivors of
      breast cancer.
AB  - Approximately 6% of invasive breast cancer is diagnosed in women younger than age
      40 of age childbearing potential. Cancer-directed therapies can cause hormonal
      and anatomical changes that negatively affect the reproductive potential of young
      survivors of breast cancer. Recent national guidelines on fertility preservation
      are widely available. However, gaps in care exist in the interdisciplinary
      evidence-based management of young survivors of breast cancer with fertility and
      parenting concerns after cancer treatment. 

PMID- 24689364
TI  - Rationally designed peptoids modulate aggregation of amyloid-beta 40.
AB  - Alzheimer's disease (AD) is the most common form of dementia and the sixth
      leading cause of death in the United States. Plaques composed of aggregated
      amyloid-beta protein (Abeta) accumulate between the neural cells in the brain and
      are associated with dementia and cellular death. Many strategies have been
      investigated to prevent Abeta self-assembly into disease-associated beta-sheet
      amyloid aggregates; however, a promising therapeutic has not yet been identified.
      In this study, a peptoid-based mimic of the peptide KLVFF (residues 16-20 of
      Abeta) was tested for its ability to modulate Abeta aggregation. Peptoid JPT1
      includes chiral, aromatic side chains to induce formation of a stable helical
      secondary structure that allows for greater interaction between the aromatic side
      chains and the cross beta-sheet of Abeta. JPT1 was found to modulate Abeta40
      aggregation, specifically decreasing lag time to beta-sheet aggregate formation
      as well as the total number of fibrillar, beta-sheet structured aggregates
      formed. These results suggest that peptoids may be able to limit the formation of
      Abeta aggregates that are associated with AD. 

PMID- 24689365
TI  - Evaluation in mice of the immunogenicity and protective efficacy of a tetravalent
      subunit vaccine candidate against dengue virus.
AB  - A dengue vaccine must induce protective immunity against the four serotypes of
      the virus. Our group has developed chimeric proteins consisting of the protein
      P64k from Neisseria meningitidis and the domain III from the four viral envelope
      proteins. In this study, the immunogenicity of a tetravalent vaccine formulation
      using aluminum hydroxide as adjuvant was evaluated in mice. After three doses,
      neutralizing antibody titers were detected against the four viral serotypes, the
      lowest seroconversion rate being against dengue virus serotype 4. One month after
      the last dose, immunized animals were challenged with infective virus, and
      partial but statistically significant protection was found to have been achieved.
      Based on these results, further studies in mice and non-human primates using this
      tetravalent formulation in a prime-boost strategy with attenuated viruses are
      strongly recommended. 

PMID- 24689369
TI  - Race trouble: attending to race and racism in online interaction.
AB  - This article advocates the concept of race trouble as a way of synthesizing
      variation in racial discourse, and as a way of studying how social interaction
      and institutional life continue to be organized by conceptions of 'race' and
      'racism'. Our analysis of an online discussion at a South African University
      about the defensibility of a characterization of (black) student protesters as
      'savages' revealed a number of familiar strategies: participants avoided explicit
      racism, denied racism, and denied racism on behalf of others. However, the aim of
      this analysis was not to identify the 'real' racism, but to show how race and
      racism were used in the interaction to develop perspectives on transformation in
      the institution, to produce social division in the University, and to create
      ambivalently racialized and racializing subject positions. We demonstrate how,
      especially through uses of deracialized discourse, participants' actions were
      observably shaped by the potential ways in which others could hear 'race' and
      'racism'. Race trouble thus became manifest through racial suggestion, allusion,
      innuendo, and implication. We conclude with a call to social psychologists to
      study the ways in which meanings of 'race' and 'racism' are forged and contested
      in relation to each other. 

PMID- 24689367
TI  - Prostaglandin therapy during the proliferative phase improves pregnancy rates
      following frozen embryo transfer in a hormone replacement cycle.
AB  - AIM: To determine the efficacy of prostaglandin administration during the
      proliferative phase in order to improve pregnancy rates following frozen embryo
      transfer during a hormone replacement cycle (HRC). METHODS: From September 2010
      through March 2012, patients (n = 135) were recruited who had undergone oocyte
      retrieval during a stimulation cycle with clomiphene and had deferred fresh
      embryo transfer (ET) due to a thin uterine endometrium. All patients were less
      than 40 years of age and underwent thawed ET following all embryo
      cryopreservation, and were randomly divided into two groups for thawed ET using a
      conventional hormone replacement cycle with or without prostaglandin derivatives
      (prostaglandin or conventional group). Prostaglandin derivatives were
      administrated during the proliferative phase. Pregnancy and implantation rates
      following frozen ET were compared between the two groups. RESULTS: Although the
      endometrial thickness on the day of ET was similar for the prostaglandin and
      conventional groups, the pregnancy and implantation rates for the prostaglandin
      group were 40.0% and 22.0%, respectively, which was significantly higher than the
      rates for the conventional group (P < 0.01). CONCLUSION: Among patients who
      avoided fresh ET due to a thin endometrium, the pregnancy rate following a thawed
      cycle was low. However, it was improved when prostaglandin derivatives were used
      during the proliferative phase.

PMID- 24689368
TI  - Changes in chemical permeation of disposable latex, nitrile, and vinyl gloves
      exposed to simulated movement.
AB  - Glove movement can affect chemical permeation of organic compounds through
      polymer glove products. However, conflicting reports make it difficult to compare
      the effects of movement on chemical permeation through commonly available glove
      types. The aim of this study was to evaluate the effect of movement on chemical
      permeation of an organic solvent through disposable latex, nitrile, and vinyl
      gloves. Simulated whole-glove permeation testing was conducted using ethyl
      alcohol and a previously designed permeation test system. With exposure to
      movement, a significant decrease (p <= 0.001) in breakthrough time (BT) was
      observed for the latex (-23%) and nitrile gloves (-31%). With exposure to
      movement, only the nitrile glove exhibited a significant increase (p <= 0.001) in
      steady-state permeation rate (+47%) and cumulative permeation at 30 min (+111%).
      Even though the nitrile glove provided optimum chemical resistance against ethyl
      alcohol, it was most affected by movement. With exposure to movement, the latex
      glove was an equivalent option for overall worker protection, because it was less
      affected by movement and the permeation rate was lower than that of the nitrile
      glove. In contrast, the vinyl glove was the least affected by movement, but did
      not provide adequate chemical resistance to ethyl alcohol in comparison with the
      nitrile and latex gloves. Glove selection should take movement and polymer type
      into account. Some glove polymer types are less affected by movement, most
      notably the latex glove in this test. With nitrile gloves, at least a factor of
      three should be used when attempting to assign a protection factor when
      repetitive hand motions are anticipated. Ultimately, the latex gloves
      outperformed nitrile and vinyl in these tests, which evaluated the effect of
      movement on chemical permeation. Future research should aim to resolve some of
      the observed discrepancies in test results with latex and vinyl gloves.

PMID- 24689371
TI  - Nurses should have a say in how the NMC is run.

PMID- 24689383
TI  - Relaxation of the rules on visiting hours shows 'substantial progress'.

PMID- 24689370
TI  - Mast cells are activated by Staphylococcus aureus in vitro but do not influence
      the outcome of intraperitoneal S. aureus infection in vivo.
AB  - Staphylococcus aureus is a major pathogen that can cause a broad spectrum of
      serious infections including skin infections, pneumonia and sepsis. Peritoneal
      mast cells have been implicated in the host response towards various bacterial
      insults and to provide mechanistic insight into the role of mast cells in
      intraperitoneal bacterial infection we here studied the global effects of S.
      aureus on mast cell gene expression. After co-culture of peritoneal mast cells
      with live S. aureus we found by gene array analysis that they up-regulate a
      number of genes. Many of these corresponded to pro-inflammatory cytokines,
      including interleukin-3, interleukin-13 and tumour necrosis factor-alpha. The
      cytokine induction in response to S. aureus was confirmed by ELISA. To study the
      role of peritoneal mast cells during in vivo infection with S. aureus we used
      newly developed Mcpt5-Cre(+) * R-DTA mice in which mast cell deficiency is
      independent of c-Kit. This is in contrast to previous studies in which an impact
      of mast cells on bacterial infection has been proposed based on the use of mice
      whose mast cell deficiency is a consequence of defective c-Kit signalling.
      Staphylococcus aureus was injected intraperitoneally into mast-cell-deficient
      Mcpt5-Cre(+) * R-DTA mice using littermate mast-cell-sufficient mice as controls.
      We did not observe any difference between mast-cell-deficient and control mice
      with regard to weight loss, bacterial clearance, inflammation or cytokine
      production. We conclude that, despite peritoneal mast cells being activated by S.
      aureus in vitro, they do not influence the in vivo manifestations of
      intraperitoneal S. aureus infection.

PMID- 24689388
TI  - Nurse calls on PM to investigate 'dysfunctional whistleblowing'.

PMID- 24689389
TI  - Unequal pay for work of equal value - Mr Hunt's gift to nurses.

PMID- 24689395
TI  - Gout.

PMID- 24689396
TI  - Restraint is a last resort, use it rarely and wisely.
AB  - Restrictive intervention is a difficult area. Some inappropriate actions are
      taken by healthcare professionals because of a perceived need for a 'quick fix'.
      Restraint should always be proportionate and used as a last resort.

PMID- 24689397
TI  - Patients take the driving seat.
AB  - Service users can express what is important to them and ensure the care they
      receive matches their preferences when a care and support planning approach is
      used. The care plan is drawn up by the patient with a professional partner, and
      owned by the patient. The approach improves outcomes.

PMID- 24689398
TI  - Your vote matters.
AB  - Turnout in the UK countries for elections to the European Parliament is usually
      low. RCN advisers argue that the EU has made a positive difference to nurses and
      patients in the UK and call on nurses to vote in the European elections on May 22
      and make their voices heard.

PMID- 24689413
TI  - Mental health staff know how harmful prison books ban will be.

PMID- 24689414
TI  - NMC needs to cut its cloth to fit its means, not tap up others.

PMID- 24689415
TI  - Fee increase is a mere distraction from the bigger problem of pay.

PMID- 24689416
TI  - Why does the nurse regulator need to build up a L10 million reserve?

PMID- 24689419
TI  - Help us to overturn prohibition on sending books to prisoners.

PMID- 24689418
TI  - Thanks to RCN and unison for their support of NHS Direct members.

PMID- 24689420
TI  - A clear example of how and why campaigning can get results.

PMID- 24689421
TI  - Managing a major incident in the critical care unit.
AB  - This article analyses recent major incidents using a standardised structured
      approach and is relevant to nurses working in the critical care unit. Information
      on responding to a major incident is provided, and the need to support staff
      after an incident, especially critical care personnel, is discussed. The main
      themes associated with assisting critical care nurses in preparing to deal with a
      broad range of situations which they may be required to respond to is described
      and an overview of major incident training for nurses is provided. 

PMID- 24689422
TI  - Nervous system: part 1.
AB  - This article, which forms part of the life sciences series and is the first of
      three articles on the nervous system, explores the major divisions of the nervous
      system and their functions. The basic structure of a nerve cell is described, and
      generation and conduction of nerve impulses is discussed. Blood supply to the
      brain is also covered. The second article will examine the central nervous system
      (CNS) in greater detail, including protection of the CNS, and the structure and
      function of the cerebral cortex and cerebellum. The third article will examine
      the peripheral nervous system and the autonomic nervous system, and provides an
      overview of some of the disorders of the nervous system. 

PMID- 24689423
TI  - Care of patients undergoing day case inguinal hernia repair.
AB  - Inguinal hernia repair is a common operation often performed as a day case
      procedure. Day surgery is popular with patients and offers many benefits. This
      article outlines the most common forms of hernia repair and discusses the need
      for general or local anaesthesia. Basic principles of day surgery management,
      including patient selection criteria, pain relief, post-operative information,
      nurse-led discharge and subsequent aftercare are described, many of which are
      applicable to other day surgery procedures. 

PMID- 24689424
TI  - Pressure ulcer prevention.

PMID- 24689425
TI  - Preparing for success.

PMID- 24689426
TI  - Will you be a hero or a zero?

PMID- 24689429
TI  - Student life - the right care combination.

PMID- 24689430
TI  - Generation of a safe Salmonella Gallinarum vaccine candidate that secretes an
      adjuvant protein with immunogenicity and protective efficacy against fowl
      typhoid.
AB  - We constructed a live, attenuated Salmonella Gallinarum (SG) that secretes heat
      labile enterotoxin B subunit protein (LTB), and evaluated this strain as a new
      vaccine candidate by assessing its safety, immunogenicity and protective efficacy
      against fowl typhoid. An asd(+) p15A ori low-copy plasmid containing eltB
      encoding LTB was transformed into a DeltalonDeltacpxRDeltaasd SG (JOL967) to
      construct the candidate, JOL1355. In Experiments 1 and 2, birds were orally
      immunized with JOL1355 at 4 weeks of age, while control birds were inoculated
      with sterile phosphate-buffered saline. In Experiment 2, the birds of both groups
      were orally challenged with a virulent SG at 8 weeks of age. In Experiment 1,
      examination for safety revealed that the immunized group did not show any
      bacterial counts of the vaccine candidate in the liver and spleen. Birds
      immunized with the vaccine candidate showed a significant increase in systemic
      IgG and mucosal secretory IgA levels in Experiment 2. In addition, the lymphocyte
      proliferation response and the numbers of CD3(+)CD4(+) and CD3(+)CD8(+) T cells
      were also significantly elevated in the immunized group, which indicated that the
      candidate also induced cellular immune responses. In the protection assay,
      efficient protection with only 16% mortality in the immunized group was observed
      against challenge compared with 76% mortality in the control group. These results
      indicate that the live, attenuated SG secreting LTB can be a safe vaccine
      candidate. In addition, it can induce humoral and cellular immune responses and
      can efficiently reduce mortality of birds exposed to fowl typhoid. 

PMID- 24689431
TI  - Virulence genes, antibiotic resistance and integrons in Escherichia coli strains
      isolated from synanthropic birds from Spain.
AB  - The aim of this study was to determine the presence of virulence genes and
      antibiotic resistance profiles in 164 Escherichia coli strains isolated from
      birds (feral pigeons, hybrid ducks, house sparrows and spotless starlings)
      inhabiting urban and rural environments. A total of eight atypical
      enteropathogenic E. coli strains were identified: one in a house sparrow, four in
      feral pigeons and three in spotless starlings. Antibiotic resistance was present
      in 32.9% (54) of E. coli strains. The dominant type of resistance was to
      tetracycline (21.3%), ampicillin (19.5%) and sulfamethoxazole (18.9%). Five
      isolates had class 1 integrons containing gene cassettes encoding for
      dihydrofolate reductase A (dfrA) and aminoglycoside adenyltransferase A (aadA),
      one in a feral pigeon and four in spotless starlings. To our knowledge, the
      present study constitutes the first detection of virulence genes from E. coli in
      spotless starlings and house sparrows, and is also the first identification
      worldwide of integrons containing antibiotic resistance gene cassettes in E. coli
      strains from spotless starlings and pigeons. 

PMID- 24689432
TI  - Molecular mechanisms of quinolone, macrolide, and tetracycline resistance among
      Campylobacter isolates from initial stages of broiler production.
AB  - The aim of this study was to investigate the resistance mechanisms of quinolones,
      macrolides and tetracycline in campylobacter isolates from grandparent and parent
      broiler breeders in Spain. Twenty-six isolates were investigated for quinolone
      resistance, three isolates for macrolide resistance and 39 for tetracycline
      resistance. All of the quinolone-resistant isolates possessed the mutation
      Thr86Ile in the quinolone resistance-determining region of gyrA and one isolate
      possessed the mutation Pro104Ser. Only one Campylobacter coli population (defined
      by restriction fragment length polymorphism-polymerase chain reaction of flaA and
      pulsed field gel electrophoresis) was resistant to erythromycin, and the mutation
      A2075G (23S rDNA) was responsible for macrolide resistance. The tetO gene was
      found in all of the tetracycline-resistant isolates. Twenty-two out of the 39
      isolates investigated by Southern blot possessed chromosomic location of tetO and
      17 were located on plasmids. Most of the plasmids with tetO were of around 60 kb
      and conjugation was demonstrated in a selection of them. In conclusion, we showed
      that Thr86Ile is highly prevalent in quinolone-resistant isolates as well as
      mutation A2075G in macrolide-resistant isolates of poultry origin. More
      variability was found for tetO. The possibility of horizontal transmission of
      tetO among campylobacter isolates is also an issue of concern in public health. 

PMID- 24689433
TI  - Molecular evolution of H5N1 highly pathogenic avian influenza viruses in
      Bangladesh between 2007 and 2012.
AB  - In Bangladesh, highly pathogenic avian influenza (HPAI) virus subtype H5N1 was
      first detected in February 2007. Since then the virus has become entrenched in
      poultry farms of Bangladesh. There have so far been seven human cases of H5N1
      HPAI infection in Bangladesh with one death. The objective of the present study
      was to investigate the molecular evolution of H5N1 HPAI viruses during 2007 to
      2012. Partial or complete nucleotide sequences of all eight gene segments of two
      chicken isolates, five gene segments of a duck isolate and the haemagglutinin
      gene segment of 18 isolates from Bangladesh were established in the present study
      and subjected to molecular analysis. In addition, full-length sequences of
      different gene segments of other Bangladeshi H5N1 isolates available in GenBank
      were included in the analysis. The analysis revealed that the first introduction
      of clade 2.2 virus in Bangladesh in 2007 was followed by the introduction of
      clade 2.3.2.1 and 2.3.4 viruses in 2011. However, only clade 2.3.2.1 viruses
      could be isolated in 2012, indicating progressive replacement of clade 2.2 and
      2.3.4 viruses. There has been an event of segment re-assortment between H5N1 and
      H9N2 viruses in Bangladesh, where H5N1 virus acquired the PB1 gene from a H9N2
      virus. Point mutations have accumulated in Bangladeshi isolates over the last 5
      years with potential modification of receptor binding site and antigenic sites.
      Extensive and continuous molecular epidemiological studies are necessary to
      monitor the evolution of circulating avian influenza viruses in Bangladesh. 

PMID- 24689434
TI  - The use of surgical Nd:YAG laser in an oral pyogenic granuloma: a case report.
AB  - Pyogenic granuloma is a benign, non-neoplastic, mucocutaneous lesion and is
      especially common on the tongue, lips, and gums. This case report presents a
      large oral pyogenic granuloma of the gingiva and the surgical treatment of this
      lesion with Nd:YAG laser. A 14-year-old female patient referred with a complaint
      of a swelling and growth on the buccal side of her mandibular left premolar
      teeth. A comprehensive intraoral examination revealed a localized gingival mass
      between mandibular left premolar teeth on the buccal aspect. The treatment
      selected was surgical removal using Nd:YAG laser with the following irradiation
      parameters: power output 4 W, energy 100 mJ, frequency 40 Hz, and pulsed emission
      mode. During surgery, complications including hemorrhage were not observed, and
      no scarring developed after surgery. The excised area gradually improved within 1
      month. The use of Nd:YAG laser in the treatment of pyogenic granuloma reduced
      bleeding during surgery, with a consequent reduction in operating time, promoted
      rapid postoperative hemostasis, and has better patient acceptance.

PMID- 24689436
TI  - Speech intelligibility while wearing full-facepiece air-purifying respirators.
AB  - Intelligible speech communication while wearing air-purifying respirators is
      critical for law enforcement officers, particularly when they are communicating
      with each other or the public. The National Institute for Occupational Safety and
      Health (NIOSH) requires a 70% overall performance rating to pass speech
      intelligibility certification for commercial chemical, biological, radiological,
      and nuclear air-purifying respirators. However, the speech intelligibility of
      certified respirators is not reported and the impact on operational performance
      is unknown. The objective of this effort was to assess the speech intelligibility
      of 12 certified air-purifying respirators and to predict their impact on
      operational performance. The NIOSH respirator certification standard testing
      procedures were followed. Regression equations were fit to data from studies that
      examined the impact of degraded speech intelligibility on operational performance
      of simple and complex missions. The impact of the tested respirators on
      operational performance was estimated from these equations. Performance ratings
      observed for each respirator were: MSA Millennium (90%), 3M FR-M40 (88%), MSA
      Ultra Elite (87%), Scott M110 (86%), North 5400 (85%), Scott M120 (85%), Avon C50
      (84%), Avon FM12 (84%), Survivair Optifit (81%), Drager CDR 4500 (81%), Peltor
      AOSafety M-TAC (79%), and 3M FR-7800B (78%). The Millennium and FR-M40 had
      statistically significantly higher scores than the FR-7800B. The Millennium also
      scored significantly higher than the M-TAC. All of the tested respirators were
      predicted to have little impact on simple and complex mission performance times
      and on simple mission success rate. However, the regression equations showed that
      75% of missions that require complex communications would be completed while
      wearing the Millennium, FR-M40, or Ultra Elite but that only 60% would be
      completed successfully while wearing the FR-7800B. These results suggest that
      some certified respirators may have a greater impact on speech communications
      than others. 

PMID- 24689437
TI  - Secondary metabolites from the endophytic Botryosphaeria dothidea of Melia
      azedarach and their antifungal, antibacterial, antioxidant, and cytotoxic
      activities.
AB  - Two new metabolites, an alpha-pyridone derivative, 3-hydroxy-2-methoxy-5
      methylpyridin-2(1H)-one (1), and a ceramide derivative, 3-hydroxy-N-(1-hydroxy-3
      methylpentan-2-yl)-5-oxohexanamide (2), and a new natural product, 3-hydroxy-N-(1
      hydroxy-4-methylpentan-2-yl)-5-oxohexanamide (3), along with 15 known compounds
      including chaetoglobosin C (7) and chaetoglobosin F (8) were isolated from the
      solid culture of the endophytic fungus Botryosphaeria dothidea KJ-1, collected
      from the stems of white cedar (Melia azedarach L). The structures were elucidated
      on the basis of spectroscopic analysis (1D and 2D NMR experiments and by mass
      spectrometric measurements), and the structure of 1 was confirmed by X-ray single
      crystal diffraction. These metabolites were evaluated in vitro for antimicrobial,
      antioxidant, and cytotoxicity activities. Pycnophorin (4) significantly inhibited
      the growth of Bacillus subtilis and Staphyloccocus aureus with equal minimum
      inhibitory concentration (MIC) values of 25 MUM. Stemphyperylenol (5) displayed a
      potent antifungal activity against the plant pathogen Alternaria solani with MIC
      of 1.57 MUM comparable to the commonly used fungicide carbendazim. Both altenusin
      (9) and djalonensone (10) showed markedly DPPH radical scavenging activities. In
      addition, stemphyperylenol (5) and altenuene (6) exhibited strong cytotoxicity
      against HCT116 cancer cell line with a median inhibitory concentration (IC50)
      value of 3.13 MUM in comparison with the positive control etoposide (IC50 = 2.13
      MUM). This is the first report of the isolation of these compounds from the
      endophytic B. dothidea. 

PMID- 24689438
TI  - Improved in vitro efficacy of gold nanoconstructs by increased loading of G
      quadruplex aptamer.
AB  - This paper describes how in vitro efficacy of aptamer-loaded gold nanostars (Apt
      AuNS) can be enhanced by the increased loading of a G-quadruplex homodimer AS1411
      (Apt) on the AuNS surface. In a low pH buffer environment, the loading density of
      Apt on AuNS was increased up to 2.5 times that obtained using the conventional
      salt-aging process. These highly loaded AuNS nanoconstructs (*Apt-AuNS) were
      taken up in pancreatic cancer and fibrosarcoma cells ca. 2 times more and at
      faster rates compared to Apt-AuNS. When a similar number of AuNS carriers was
      internalized by the cancer cells, the amount of AS1411 delivered via *Apt-AuNS
      was effectively double that of Apt-AuNS, and *Apt-AuNS resulted in an average of
      42% increase in cell death. These results suggest that increasing the loading
      density on AuNS could provide a simple means to improve uptake as well as in
      vitro efficacy of the nanoconstructs in cancer cells. 

PMID- 24689440
TI  - Factors relating to perioperative experience of older persons undergoing joint
      replacement surgery: an integrative literature review.
AB  - PURPOSE: The purpose of this literature review was to examine factors relating to
      the perioperative experience of older persons undergoing total hip and knee
      replacement surgery resulting from osteoarthritis. METHOD: A literature search
      was undertaken using databases CINAHL, PubMed, Scopus and Web of Science to
      provide relevant research articles. Articles were included if they examined the
      factors relating to the HRQOL, QOL and perioperative experience of older persons
      undergoing joint replacement surgery resulting from osteoarthritis. The use of
      Joanna Briggs Institute's critical appraisal checklist facilitated a systematic
      appraisal of studies with regard to the scientific rigor of the studies. RESULTS:
      Twenty-two publications were categorized into one main theme: "factors relating
      to perioperative experience" subcategorized into eight subthemes: "waiting time",
      "pain and disability", "mental health", "race/ethnicity, age and gender", "body
      image", "coping and social support", "patient education" and "care continuity".
      CONCLUSION: There is a need to conduct further research to examine the
      perioperative experience of older persons undergoing joint replacement surgery,
      in particular, the lived perioperative experience of a diverse race, ethnicity
      and culture in an Asian population. Implications for Rehabilitation Healthcare
      services should remain focused on reducing waiting time as prolonged waiting time
      for joint replacement surgery was detrimental to patients' HRQOL. Healthcare
      professionals need to identify strategies to improve the perioperative pain
      experience through patient education on pain management and positive social
      support to support the process of recovery. Patients' expectations of pain and
      their process of recovery were closely linked to patient education. One model of
      patient education that was seen to be successful and linked to good post
      operative outcomes was care continuity model. Being actively involved in the care
      continuity results in better post-operative outcomes for the patient and their
      family.

PMID- 24689439
TI  - Regio- and diastereoselective construction of alpha-hydroxy-delta-amino ester
      derivatives via 1,4-conjugate addition of beta,gamma-unsaturated N
      sulfonylimines.
AB  - A first example of 1,4-conjugate addition of beta,gamma-unsaturated N
      sulfonylimines via the oxonium ylides trapping process was developed. This method
      afforded a novel and efficient access for the high regio- and diastereoselective
      construction of alpha-hydroxyl-delta-amino esters derivatives, which exhibit
      inhibitory activity on PTP1B and SIRT1 enzymes in vitro. The synthetic potentials
      and the biological activity of the resulting products were well demonstrated to
      be promising for drug discovery. 

PMID- 24689441
TI  - A rehabilitation unit at night: environmental characteristics of patient rooms.
AB  - PURPOSE: The aim of this study was first of all to investigate the sound, light,
      temperature and humidity levels in a rehabilitation ward and to establish whether
      the measured levels were within the recommended levels or not; secondly to
      explore influence of the type of the patient rooms on obtained measurements.
      METHODS: Measurements of environmental characteristics were recorded on three non
      consecutive nights by data loggers in a 12-bedded residential neurological
      rehabilitation unit for patients with disorders of consciousness. The obtained
      measurements were compared with the recommendations of the World Health
      Organization and the Society of Light and Lighting. RESULTS: Recordings were
      within recommended levels for light and humidity overnight. Average noise levels
      were above the recommended levels. There were abrupt increases of light and noise
      levels which were high enough to cause sleep fragmentation. Mean temperature
      levels were higher than recommended. CONCLUSIONS: Our results indicated that the
      patients are at risk of disturbed sleep for the duration of their stay in
      rehabilitation unit. Exposure to generally high noise levels, as well as the
      sudden increases of noise and light intensities can prevent reaching restful
      night-time sleep and may negatively impact on rehabilitation process due to
      impaired memory, learning and well-being. Implications for Rehabilitation
      Standards for ward based hospital environments to minimize sleep disturbance
      exist and can be used to examine the environmental characteristics of patients'
      rooms in different healthcare settings including rehabilitation units. This study
      shows that measurements of environmental factors were not always within the
      recommended levels in the rehabilitation unit and presence of abrupt increase of
      noise and light levels are likely to cause sleep disturbance of patients.
      Assessment of current practice, education and training of night staff to raise
      awareness on importance of sleep and environmental factors and development of
      strategies are required in order to improve quality of sleep in rehabilitation
      settings.

PMID- 24689443
TI  - Growth of bubbles on a solid surface in response to a pressure reduction.
AB  - A diffusion-controlled method is presented to study the growth of bubbles on a
      solid surface. The bubbles are nucleated spontaneously on a hydrophobic smooth
      surface in response to a sudden pressure reduction and then grow with an
      expanding contact line. The evolution of the bubbles in the early stage is found
      to grow with a constant bubble radius and a decreasing contact angle, while the
      bubbles continue their growth with a constant contact angle and an increasing
      bubble radius after the contact angle reaches its equilibrium value. A total
      variation of about 60 degrees  of the contact angle is observed during the growth
      of the bubbles with the size scale of 10-100 MUm in radius. The growing process
      is described by the diffusion theory with the validation of the growth constant. 

PMID- 24689444
TI  - Transthyretin-derived peptides as beta-amyloid inhibitors.
AB  - Self-association of beta-amyloid (Abeta) into soluble oligomers and fibrillar
      aggregates is associated with Alzheimer's disease pathology, motivating the
      search for compounds that selectively bind to and inhibit Abeta oligomerization
      and/or neurotoxicity. Numerous small-molecule inhibitors of Abeta aggregation or
      toxicity have been reported in the literature. However, because of their greater
      size and complexity, peptides and peptidomimetics may afford improved specificity
      and affinity as Abeta aggregation modulators compared to small molecules. Two
      divergent strategies have been employed in the search for peptides that bind
      Abeta: (i) using recognition domains corresponding to sequences in Abeta itself
      (such as KLVFF) and (ii) screening random peptide-based libraries. In this study,
      we propose a third strategy, specifically, designing peptides that mimic binding
      domains of Abeta-binding proteins. Transthyretin, a plasma transport protein that
      is also relatively abundant in cerebrospinal fluid, has been shown to bind to
      Abeta, inhibit aggregation, and reduce its toxicity. Previously, we identified
      strand G of transthyretin as a specific Abeta binding domain. In this work we
      further explore and define the necessary features of this binding domain. We
      demonstrate that peptides derived from transthyretin bind Abeta and inhibit its
      toxicity. We also show that, although both transthyretin and transthyretin
      derived peptides bind Abeta and inhibit toxicity, they differ significantly in
      their effect on Abeta aggregation. 

PMID- 24689445
TI  - Age at first drink, drinking, binge drinking, and DSM-5 alcohol use disorder
      among Hispanic national groups in the United States.
AB  - BACKGROUND: This article examines age at first drink and adult drinking, binge
      drinking and DSM-5 alcohol use disorder (AUD) among U.S. Hispanic national
      groups. METHODS: Respondents come from 2 independent studies. The Hispanic
      Americans Baseline Alcohol Survey used a multistage cluster sample design to
      interview 5,224 individuals 18 years of age and older selected from the household
      population in Miami, New York, Philadelphia, Houston, and Los Angeles.
      Respondents in the border area (N = 1,307) constituted a household probability
      sample of Mexican Americans living on U.S. counties that border Mexico. In both
      surveys, data were collected during computer-assisted interviews conducted in
      respondents' homes. The Hispanic American Baseline Alcohol Survey and the border
      sample response rates were 76 and 67%, respectively. RESULTS: U.S.-born Hispanics
      begin drinking at a younger age than those who are foreign-born, independent of
      national group. Among foreign-born Hispanics, age of arrival in the United States
      is not associated with age at first drink. Results support the hypothesis that a
      younger age at first drink is associated with a higher mean volume of drinking, a
      higher probability of bingeing, and a higher probability of DSM-5 AUD. But the
      results do not show a clear pattern by which a particular national group would
      consistently show no associations or stronger associations between age at first
      drink and the alcohol-related outcomes under consideration. CONCLUSIONS: An
      earlier age at first drinking is positively associated with heavier drinking
      patterns among U.S. Hispanics. However, as in other areas of alcohol
      epidemiology, here too there is considerable variation in age at first drink and
      drinking across Hispanic national groups.

PMID- 24689446
TI  - Varicose veins of the legs among nurses: Occupational and demographic
      characteristics.
AB  - This study aims to determine the relationship between occupational and
      demographic hazards that characterize varicose veins (VV) in the legs and their
      intensity among nurses.A cross-sectional study was carried out among 203 nurses
      from three general hospitals in Amol, Iran. The required subjects' information
      was collected through a self-filled questionnaire and the physical examination of
      the VV intensity was based on the Clinical finding using the Etiology, Anatomic
      finding, Pathophysiological standards. The prevalence of VV, with different
      degrees, was 72.4% (95% CI 65.7-78.4), with women having a higher prevalence
      compared with men (77.9% vs. 56.9%, P = 0.004). The other non-interventional risk
      variable was having longer years of service. Interventional variables were long
      standing hours, overtime work and body mass index status. This study had
      determined the occupational risk variables on VV which could be interventional in
      improving the working nurses' environment and quality of life for their long-term
      career. 

PMID- 24689447
TI  - Parenthood in long-term survivors after CHOP with or without etoposide treatment
      for aggressive lymphoma - response to Meissner et al.

PMID- 24689448
TI  - Combining experimental evolution and field population assays to study the
      evolution of host range breadth.
AB  - Adapting to specific hosts often involves trade-offs that limit performance on
      other hosts. These constraints may either lead to narrow host ranges (i.e.
      specialists, able to exploit only one host type) or wide host ranges often
      leading to lower performance on each host (i.e. generalists). Here, we combined
      laboratory experiments on field populations with experimental evolution to
      investigate the impact of adaptation to the host on host range evolution and
      associated performance over this range. We used the two-spotted spider mite,
      Tetranychus urticae, a model organism for studies on the evolution of
      specialization. Field mite populations were sampled on three host plant species:
      tomato, citrus tree and rosebay (Nerium oleander). Testing these populations in
      the laboratory revealed that tomato populations of mites could exploit tomato
      only, citrus populations could exploit citrus and tomato whereas Nerium
      populations could exploit all three hosts. Besides, the wider niche ranges of
      citrus and Nerium populations came at the cost of low performance on their non
      native hosts. Experimental lines selected to live on the same three host species
      exhibited similar patterns of host range and relative performance. This result
      suggests that adaptation to a new host species may lead to wider host ranges but
      at the expense of decreased performance on other hosts. We conclude that
      experimental evolution may reliably inform on evolution in the field. 

PMID- 24689449
TI  - The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ
      induced diabetic rats.
AB  - Recently the role of adipocytokines in relationship to incidence of diabetes has
      been demonstrated. One of the medicinal plants that are used in the treatment of
      diabetes is stevia. This study investigates the effect of stevia on serum omentin
      and visfatin levels as novel adipocytokines in diabetic induced rats to find
      potential mechanisms for the anti hyperglycemic effect of stevia. Forty male
      wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal
      injection of streptozotocin (STZ). The animals were divided into 5 groups of 8.
      Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were
      treated with distilled water, and the rats in the treated groups, group 3 (T250),
      group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at
      9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study
      significant reductions in fasting blood sugar (FBS), the homeostasis model
      assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase
      (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2.
      Pancreatic histopathology slides demonstrated that stevia extract did not induce
      any increase in the number of beta-cells. The conclusion is that prescription of
      stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly
      via activating insulin sensitivity and lowering blood glucose in STZ-induced
      diabetic rats.

PMID- 24689450
TI  - Recurrent miscarriage is associated with a decline of decidual natural killer
      cells expressing killer cell immunoglobulin-like receptors specific for human
      leukocyte antigen C.
AB  - AIM: To investigate the relationship between natural killer (NK) cell phenotype
      and recurrent miscarriage (RM). METHODS: We studied killer cell immunoglobulin
      like receptor (KIR) expression on decidual NK cells in women with RM. RESULTS:
      The expression of KIR2DL1/S1 on CD56(+) CD16(-) NK cells in the deciduas of these
      women was significantly lower than in that of control subjects (P = 0.026). There
      was a significant decline in the frequency of CD56(+) CD16(-) NK cells staining
      for KIR2DL1/S1 and KIR2DL2/S2/L3 throughout the first trimester in patients (P <
      0.05). Furthermore, by stratification of the women in three groups according to
      gestational stage, it was found that KIR2DL1/S1 expressing NK cells were
      significantly decreased in all groups, especially around gestational days 50-70
      (P = 0.010). CONCLUSION: This is the first report to demonstrate that RM is
      associated with a decline in the frequency of decidual NK cells expressing KIR
      specific for human leukocyte antigen (HLA)-C, and in which gestational stage was
      considered. The results suggest that KIR phenotype contributes to the
      pathogenesis of the disease, and that assessment of KIR may serve as a diagnostic
      tool.

PMID- 24689451
TI  - Bioavailability of iron, zinc, and provitamin A carotenoids in biofortified
      staple crops.
AB  - International research efforts, including those funded by HarvestPlus, a
      Challenge Program of the Consultative Group on International Agricultural
      Research (CGIAR), are focusing on conventional plant breeding to biofortify
      staple crops such as maize, rice, cassava, beans, wheat, sweet potatoes, and
      pearl millet to increase the concentrations of micronutrients that are commonly
      deficient in specific population groups of developing countries. The
      bioavailability of micronutrients in unfortified staple crops in developing
      regions is typically low, which raises questions about the efficacy of these
      crops to improve population micronutrient status. This review of recent studies
      of biofortified crops aims to assess the micronutrient bioavailability of
      biofortified staple crops in order to derive lessons that may help direct plant
      breeding and to infer the potential efficacy of food-based nutrition
      interventions. Although reducing the amounts of antinutrients and the conduction
      of food processing generally increases the bioavailability of micronutrients,
      antinutrients still possess important benefits, and food processing results in
      micronutrient loss. In general, biofortified foods with relatively higher
      micronutrient density have higher total absorption rates than nonbiofortified
      varieties. Thus, evidence supports the focus on efforts to breed plants with
      increased micronutrient concentrations in order to decrease the influence of
      inhibitors and to offset losses from processing. 

PMID- 24689452
TI  - Ecology of plant volatiles: taking a plant community perspective.
AB  - Although plants are sessile organisms, they can modulate their phenotype so as to
      cope with environmental stresses such as herbivore attack and competition with
      neighbouring plants. Plant-produced volatile compounds mediate various aspects of
      plant defence. The emission of volatiles has costs and benefits. Research on the
      role of plant volatiles in defence has focused primarily on the responses of
      individual plants. However, in nature, plants rarely occur as isolated
      individuals but are members of plant communities where they compete for resources
      and exchange information with other plants. In this review, we address the
      effects of neighbouring plants on plant volatile-mediated defences. We will
      outline the various roles of volatile compounds in the interactions between
      plants and other organisms, address the mechanisms of plant neighbour perception
      in plant communities, and discuss how neighbour detection and volatile signalling
      are interconnected. Finally, we will outline the most urgent questions to be
      addressed in the future. 

PMID- 24689453
TI  - Collagen gels and the 'Bornstein legacy': from a substrate for tissue culture to
      cell culture systems and biomaterials for tissue regeneration.
AB  - As collagen is the main structural component of connective tissues and skin, much
      effort was made in the past and still today to use it in cell culture
      applications. Moreover, collagen biomaterials are widely used in tissue
      regeneration, including the treatment of burns and chronic wounds. The great
      implications of the research carried out by Bornstein, Ehrmann and Gey on
      collagen preparations in the 1950s for cell culture and more recently tissue
      engineering and regeneration are described in this commentary. Specifically, it
      is explored why the 1958 paper on 'Reconstituted Rat-Tail Collagen Used as
      Substrate for Tissue Cultures on Coverslips in Maximow Slides and Roller Tubes'
      by M. B. Bornstein has made an invaluable contribution to the field.

PMID- 24689456
TI  - Randomised clinical trial: gluten may cause depression in subjects with non
      coeliac gluten sensitivity - an exploratory clinical study.
AB  - BACKGROUND: Current evidence suggests that many patients with self-reported non
      coeliac gluten sensitivity (NCGS) retain gastrointestinal symptoms on a gluten
      free diet (GFD) but continue to restrict gluten as they report 'feeling better'.
      AIM: To investigate the notion that a major effect of gluten in those with NCGS
      is on mental state and not necessarily on gastrointestinal symptoms. METHODS:
      Twenty-two subjects (24-62 years, five male) with irritable bowel syndrome who
      had coeliac disease excluded but were symptomatically controlled on a GFD,
      undertook a double-blind cross-over study. Participants randomly received one of
      three dietary challenges for 3 days, followed by a minimum 3-day washout before
      crossing over to the next diet. Challenge gluten-free food was supplemented with
      gluten (16 g/day), whey (16 g/day) or not supplemented (placebo). End-points
      included mental state as assessed by the Spielberger State Trait Personality
      Inventory (STPI), cortisol secretion and gastrointestinal symptoms. RESULTS:
      Gluten ingestion was associated with higher overall STPI state depression scores
      compared to placebo [M = 2.03, 95% CI (0.55-3.51), P = 0.010] but not whey [M =
      1.48, 95% CI (-0.14 to 3.10), P = 0.07]. No differences were found for other STPI
      state indices or for any STPI trait measures. No difference in cortisol secretion
      was identified between challenges. Gastrointestinal symptoms were induced
      similarly across all dietary challenges. CONCLUSIONS: Short-term exposure to
      gluten specifically induced current feelings of depression with no effect on
      other indices or on emotional disposition. Gluten-specific induction of
      gastrointestinal symptoms was not identified. Such findings might explain why
      patients with non-coeliac gluten sensitivity feel better on a gluten-free diet
      despite the continuation of gastrointestinal symptoms.

PMID- 24689455
TI  - Dendritic cells treated with crude Plasmodium berghei extracts acquire immune
      modulatory properties and suppress the development of autoimmune
      neuroinflammation.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells specifically
      targeted during Plasmodium infection. Upon infection, DCs show impaired antigen
      presentation and T-cell activation abilities. In this study, we aimed to evaluate
      whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes
      (PbX) modulate DCs phenotypically and functionally and the potential therapeutic
      usage of PbX-modulated DCs in the control of experimental autoimmune
      encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found
      that PbX-treated DCs have impaired maturation and stimulated the generation of
      regulatory T cells when cultured with naive T lymphocytes in vitro. When
      adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease
      amelioration correlated with a diminished infiltration of cytokine-producing T
      cells in the central nervous system as well as the suppression of
      encephalitogenic T cells. Our study shows that extracts obtained from P. berghei
      infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In
      addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE
      development through the suppression of specific cellular immune responses towards
      neuro-antigens. To our knowledge, this is the first study to present evidence
      that DCs treated with P. berghei extracts are able to control autoimmune
      neuroinflammation.

PMID- 24689459
TI  - Dealloying of noble-metal alloy nanoparticles.
AB  - Dealloying is currently used to tailor the morphology and composition of
      nanoparticles and bulk solids for a variety of applications including catalysis,
      energy storage, sensing, actuation, supercapacitors, and radiation damage
      resistant materials. The known morphologies, which evolve on dealloying of
      nanoparticles, include core-shell, hollow core-shell, and porous nanoparticles.
      Here we present results examining the fixed voltage dealloying of AgAu alloy
      particles in the size range of 2-6 and 20-55 nm. High-angle annular dark-field
      scanning transmission electron microcopy, energy dispersive, and electron energy
      loss spectroscopy are used to characterize the size, morphology, and composition
      of the dealloyed nanoparticles. Our results demonstrate that above the potential
      corresponding to Ag(+)/Ag equilibrium only core-shell structures evolve in the 2
      6 nm diameter particles. Dealloying of the 20-55 nm particles results and in the
      formation of porous structures analogous to the behavior observed for the
      corresponding bulk alloy. A statistical analysis that includes the composition
      and particle size distributions characterizing the larger particles demonstrates
      that the formation of porous nanoparticles occurs at a well-defined thermodynamic
      critical potential. 

PMID- 24689457
TI  - Discovery of a novel series of phenyl pyrazole inner salts based on fipronil as
      potential dual-target insecticides.
AB  - A series of novel phenyl pyrazole inner salt derivatives based on fipronil were
      designed and synthesized in the search for dual-target insecticides. These
      compounds were designed to target two families of nicotinic acetylcholine
      receptors and gamma-aminobutyric acid receptors. The insecticidal activities of
      the new compounds against diamondback moth (Plutella xylostella) were evaluated.
      The results of bioassays indicated that most of the inner salts showed moderate
      to high activities, of which the phenyl pyrazole inner salts containing quinoline
      had excellent biological activity. Previous structure-activity relationship
      studies revealed that a suitable structure of the quaternary ammonium salts was
      critical for the bioactivity of phenyl pyrazole inner salts, which contribute to
      exposing the cationic nitrogen to bind to the receptor (for instance, nicotinic
      acetylcholine receptors) and possibly interact with the receptor via hydrogen
      bonding and cooperative pi-pi interaction. The present work demonstrates that the
      insecticidal potency of phenyl pyrazole inner salts holds promise for the
      development new dual-target phenyl pyrazole insecticides. 

PMID- 24689460
TI  - Benzyl alcohol oxidation on Pd(111): aromatic binding effects on alcohol
      reactivity.
AB  - To investigate how surface oxygen participates in the reaction of important
      aromatic oxygenates, the surface chemistry of benzyl alcohol (PhCH2OH) and
      benzaldehyde (PhCHO) has been studied on oxygen-precovered Pd(111) (O/Pd(111))
      using temperature-programmed desorption (TPD) and high-resolution electron energy
      loss spectroscopy (HREELS). On both Pd(111) and O/Pd(111), TPD using isotopically
      labeled benzyl alcohol and low-temperature HREEL spectra show that the oxidation
      of benzyl alcohol proceeds through a benzyl alkoxide (PhCH2O-) intermediate to
      adsorbed benzaldehyde so that the sequence of bond scission is O-H followed by
      C(alpha)-H. In the presence of surface O, some benzaldehyde desorbs from the
      surface below 300 K, consistent with the presence of a weakly adsorbed eta(1)
      aldehyde state that is bound to the surface through its oxygen lone pair.
      Benzaldehyde also reacts with surface oxygen to produce benzoate (PhCOO-). Shifts
      in the OCO stretching frequency suggest that the benzoate orientation changes as
      the surface becomes less crowded, consistent with a strong interaction between
      the phenyl group and the surface. Adsorbed benzaldehyde and benzoate undergo
      decomposition to CO and CO2, respectively, as well as benzene. Deoxygenation of
      benzyl alcohol to toluene occurs at high coverages of benzyl alcohol when the
      relative surface O coverage is low. Experiments conducted on (18)O/Pd(111) reveal
      exchange occurring between surface O and the benzaldehyde and benzoate
      intermediates. This exchange has not been reported for other alcohols, suggesting
      that aromatic binding effects strongly influence alcohol oxidation on Pd. 

PMID- 24689462
TI  - Parenthood in long-term survivors after CHOP with or without etoposide treatment
      for aggressive lymphoma.

PMID- 24689461
TI  - Alcohol medications development: advantages and caveats of government/academia
      collaborating with the pharmaceutical industry.
AB  - The process of developing pharmacological treatments for alcohol use disorder is
      notoriously complex and challenging. The path to market is long, costly, and
      inefficient. One way of expediting and reducing the drug development process is
      through collaborations-building partnerships among government, academia,
      pharmaceutical and biotechnology companies, healthcare organizations and advocacy
      groups, and the patients (end consumers) themselves. By forging collaborations,
      particularly with pharmaceutical companies, the alcohol treatment field stands to
      reap benefits in generating new medications for use in mainstream treatment
      settings. At the same time, there are certain caveats that should be considered,
      particularly by academic researchers, before entering into such partnerships.
      This commentary examines the advantages and caveats of government and academia
      collaborations with pharmaceutical companies. 

PMID- 24689463
TI  - Monocytes from pregnant women with pre-eclampsia are polarized to a M1 phenotype.
AB  - PROBLEM: This study evaluated whether the monocyte inflammatory state in pre
      eclampsia (PE) might be associated with polarization to either M1 classically or
      M2 alternatively activated monocyte subsets. METHOD OF STUDY: Eighty-five women
      with (PE) and 52 normotensive (NT) pregnant women matched for gestational age
      were included. Expression of surface receptors characteristic of M1, such as Toll
      like receptor (TLR)2, TLR4, and CD64, or M2, such as CD163 and CD206 monocyte
      subsets were evaluated in peripheral blood monocytes by flow cytometry. Tumour
      necrosis factor-alpha (TNF-alpha), interleukin-(IL)-12p40, IL-12p70, and IL-10
      were evaluated in the supernatant of monocyte cultures by ELISA. RESULTS:
      Expression of TLR4 and CD64 by monocytes from pre-eclamptic women was
      significantly higher, while the expression of CD163 and CD206 expression was
      significantly lower compared with NT pregnant women. Endogenous production of TNF
      alpha, IL-12p40, and IL-12p70 by monocytes was increased, while synthesis of IL
      10 was lower in women with PE than in NT pregnant women. CONCLUSIONS: Monocytes
      from women with PE are classically activated, producing higher levels of pro
      inflammatory cytokines, and express surface receptors characteristic of the M1
      subset. These results provide evidence that the systemic inflammatory environment
      in PE may differentiate and polarize these cells to the M1 phenotype.

PMID- 24689464
TI  - Safety of less aggressive surgery for stage IA1 squamous cell carcinoma of the
      cervix.
AB  - AIM: To determine the risk of extracervical disease in patients with stage IA1
      squamous cell carcinoma of the cervix. METHODS: A retrospective analysis was
      performed of 169 patients who had stage IA1 cervical cancer after conization at
      Seoul National University Hospital between 1997 and 2007. RESULTS: During the
      study period, 18 patients had conization as a definite treatment and 151
      underwent subsequent surgery ranging from simple hysterectomy to radical
      hysterectomy with lymphadenectomy. Of the 151 patients who underwent subsequent
      surgery following conization, 35 (23.3%) patients underwent a simple
      hysterectomy, 20 (13.1%) a simple hysterectomy with pelvic lymphadenectomy and 96
      (63.6%) radical surgery with lymphadenectomy. No parametrial involvement or lymph
      node metastasis was noted in any of the patients who underwent parametrial
      resection and/or lymphadenectomy. Of the 62 patients who had negative resection
      margins in conization specimens, only one presented with residual tumor in
      subsequent surgery. One recurrence of the disease was identified in the total
      sample (169 patients) with a median follow-up time of 99 months. CONCLUSION: The
      risk of extracervical disease following conization is negligible, even for
      patients with positive resection margins in conization specimens. A more
      conservative and less aggressive approach may be possible for this patient
      subset.

PMID- 24689465
TI  - Time to change GP workload.

PMID- 24689471
TI  - Nursing career framework will help to stem crisis.

PMID- 24689472
TI  - The bigger picture - How to give a statement.

PMID- 24689473
TI  - Board's eye view - Gift of intuition.

PMID- 24689475
TI  - Emergency nurses: leading the development of national policy.
AB  - Roisin Devlin and Linsey Sheerin give their views on the latest moves to tackle
      poor care in North Ireland.

PMID- 24689479
TI  - Major trauma training for emergency nurses.
AB  - The Midlands regional trauma network was established in March 2012 to improve and
      standardise the care offered to patients with major trauma. This article
      discusses the results of a survey of formal training in, and self-assessed
      knowledge of, trauma management among emergency department nurses working in the
      network. Less than one third of the nurses had received formal training against
      which standards can be benchmarked, and the article recommends that nurse
      education standards are reinstated as key performance indicators in the region. 

PMID- 24689480
TI  - Improving the management and care of people with sepsis.
AB  - Many hospitals struggle to implement the full sepsis care bundle, but research
      suggests that many patients with sepsis are transported to hospital by ambulance.
      In 2011, the Scottish Ambulance Service introduced a pre-hospital sepsis
      screening tool (PSST) to expedite sepsis identification and care delivery.
      However, ambulance clinicians have reported varying degrees of interest and
      enthusiasm from hospital staff during handover. Therefore, an online survey was
      set up to investigate medical and nursing staff perceptions and experiences of
      the introduction of a PSST. This article discusses the results, which show that
      participants perceive the PSST reduces time to treatment, improves continuity of
      care, benefits patients and is accurately applied by ambulance clinicians, but
      which also highlight problems with communication. The delivery of in-hospital and
      pre-hospital sepsis care is challenging, but simple measures such as improving
      and standardising communication and alert systems between ambulance services and
      receiving hospitals could improve the clinical effects of a PSST. 

PMID- 24689481
TI  - Nurse-to-nurse referral of patients in early pregnancy.
AB  - This article describes the development, testing, evaluation and implementation of
      a nurse-to-nurse referral pathway between two trusts. The aim of the pathway is
      to improve care for women with per vaginam bleeding in early pregnancy in
      emergency situations, and the article suggests how it can be used in pre-hospital
      and primary care settings. 

PMID- 24689482
TI  - Brain tumours in children: reducing time to diagnosis.
AB  - Although the leading cause of childhood, cancer-related deaths, initial
      presentations of brain tumours can mimic less serious conditions, which can delay
      diagnosis. To reduce the time between presentation and diagnosis, the HeadSmart
      campaign has produced a symptom card to raise suspicion of brain tumours among
      healthcare professionals in all settings. This article refers to two case studies
      to describe how emergency department nurses can recognise the signs and symptoms
      of brain tumours in children. Definitive management is delivered in specialist
      centres, so safe and prompt transfer is a priority once children are stabilised. 

PMID- 24689483
TI  - Violence reduction.
AB  - As one of the first violence-reduction nurses in the country, Alice Kershberg
      gathers data on the assaults against people who have presented to her emergency
      department, and works with the police and local councils to reduce violence in
      her local community. Here, Ms Kershberg talks to Erin Dean about her role and
      aspects of her career.

PMID- 24689484
TI  - The first CNS-active carborane: A novel P2X7 receptor antagonist with
      antidepressant activity.
AB  - Relative to other polycyclic frameworks (1-3), a carborane cage (4 and Cs.5)
      exerts a significant biological effect as an inhibitor of the purinergic P2X7
      receptor (P2X7R) which allows one to target depression in vivo and thus
      demonstrate, for the first time, that a carborane has the capacity to modify CNS
      activity.

PMID- 24689485
TI  - A brief review of krill oil history, research, and the commercial market.
AB  - In the last few years there has been a noticeable increase in both the promotion
      and research of krill oil for its purported health benefits, including the
      management and treatment of conditions, such as hyperlipidemia, inflammation, and
      arthritis. Additionally, because krill oil contains the same omega-3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish and fish
      oil, krill oil is viewed as a viable alternative to fish oil to deliver the
      health benefits associated with EPA and DHA. The following review provides an
      overview of the currently available 10 peer-reviewed human clinical studies on
      krill oil, its safety, as well as a brief summary of the commercial krill oil
      market.

PMID- 24689486
TI  - Novel TBL1XR1, EPHA7 and SLFN12 mutations in a Sezary syndrome patient discovered
      by whole exome sequencing.
AB  - Sezary syndrome (SS) is an aggressive leukaemic variant of cutaneous T-cell
      lymphoma. Recurrent chromosomal aberrations have been found in SS, but the whole
      genetic mutation spectrum is unknown. To better understand the molecular
      pathogenesis of SS, we performed exome sequencing, copy number variation (CNV)
      and gene expression analysis of primary SS cells. In our index patient with
      typical SS, we found novel somatic missense mutations in TBL1XR1, EPHA7 and
      SLFN12 genes in addition to larger chromosomal changes. The mutations are located
      in biologically relevant genes affecting apoptosis and T-cell maturation. They
      may play a role in the pathobiology of the disease, but no recurrent mutations
      were discovered in nine additional patients with SS studied. Thus, screening of
      larger patient cohorts is needed to confirm their prevalence and biological
      significance in SS. 

PMID- 24689488
TI  - The peer-review process.

PMID- 24689487
TI  - Knowledge received by hospital patients--a factor connected with the patient
      centred quality of nursing care.
AB  - The main purpose of this study was to evaluate and analyse the connection between
      the level of quality of nursing care and knowledge received by patients (N = 266,
      n = 226), response rate was 85%. The data were collected using two structured
      instruments: one measuring the quality of nursing care experienced by patients
      (The Good Nursing Care Scale, GNCS) and one measuring the received knowledge of
      hospital patients (RKHP). The data were collected at one (out of five) Finnish
      university hospitals, in all medical wards during 5 weeks in 2009. A clear
      association between the level of the quality of nursing care and the level of
      received knowledge was found: on the total level of instruments, correlation was
      strong (r = 0.705). Support of empowerment (GNCS) had statistically significant
      strong correlation between biophysiological knowledge (RKHP), (r = 0.718), and
      experiential knowledge (r = 0.633), (P <= 0.01). Furthermore, there was a strong
      correlation between nursing activities and biophysiological knowledge (r =
      0.637). Higher age, sufficient advance information and better self-perceived
      health status were associated both with the level of the quality of nursing care
      and level of received knowledge. In the future, a special attention should be
      paid to the sufficient information for patients before their hospital stays. 

PMID- 24689489
TI  - Psychometric properties of the Chinese version of the Michigan Alcoholism
      Screening Test (MAST-C) for patients with alcoholism.
AB  - PURPOSE: The aim of this study was to examine the psychometric properties of the
      Chinese version of the Michigan Alcoholism Screening Test (MAST-C). DESIGN &
      METHODS: The sensitivity, specificity, and positive and negative predictive
      values for the MAST-C were examined in this study. FINDINGS: The MAST-C had an
      internal consistency of 0.83 and a test-retest reliability of 0.89. It had a good
      content validity index of 0.92. Factor analysis identified four factors and the
      optimal cutoff point for the MAST-C was a score of 6/7, which yielded a
      sensitivity of 0.92, a specificity of 0.83, a positive predictive value of 0.92,
      and a negative predictive value of 0.83. PRACTICE IMPLICATIONS: The MAST-C
      provides a fast, accurate, and sensitive method for clinically diagnosing
      alcoholism and clinical management.

PMID- 24689491
TI  - Violence and mood disorder: views and experiences of adult patients with mood
      disorders using violence toward their parents.
AB  - PURPOSE: The study explored the lived experiences of violence by patients with
      mood disorders against their biological parents who were the major caregivers (13
      parent-adult-child dyads), and sought to gain an understanding of the
      precipitating factors influencing violence. DESIGN AND METHODS: Data were
      collected by means of in-depth semi-structured interviews, managed and subjected
      to hermeneutics-guided thematic networks analysis. FINDINGS: The phenomenon was
      that violence was part of life. The four global themes were that increased
      irritability and poor impulse control lead to violence; violence causes anxiety;
      a transition from violence to nonviolence is difficult; and moving from
      descriptions of violence to analyses of violence is important. PRACTICE
      IMPLICATIONS: A comprehensive dyadic parent-child intervention program and de
      escalation techniques are suggested to manage violence substantially.

PMID- 24689490
TI  - Psychometric evaluation of a new instrument in Spanish to measure self-care
      requisites in patients with schizophrenia.
AB  - PURPOSE: The purpose of this study was to develop and validate a new instrument
      in Spanish designed to measure self-care requisites in patients with
      schizophrenia treated in the community. DESIGN AND METHODS: The first phase was
      conducted to develop the questionnaire through a panel of experts and evaluate
      for content validity. Psychometric evaluation was then conducted with a
      consecutive sample of 341 patients. FINDINGS: The scale demonstrated good
      internal consistency and stability over time. The discriminant and convergent
      validity was satisfactory. The confirmatory factor analysis showed that the
      theoretical model fits the self-care requisites proposed by Orem's nursing theory
      from which it originated. PRACTICE IMPLICATIONS: This scale is a valid and
      reliable instrument for use in clinical practice, guiding the nurse in developing
      the most appropriate care plan for each patient.

PMID- 24689492
TI  - Stability in intensive psychiatry: a concept analysis.
AB  - PURPOSE: The aim of this concept analysis is to describe, explore, and explain
      stability in the context of mental health nursing in intensive psychiatry. DESIGN
      AND METHODS: A modified version of Wilson's method of concept analysis was used.
      FINDINGS: Stability is the ability to be resistant to changes. Stability can take
      different directions after a distortion: re-gaining, neo-gaining, and apo
      gaining. Stability may also be achieved through active (adding or using power,
      making adjustments, parrying, and idling) and passive systems (environmental
      conditions and constituent materials). PRACTICE IMPLICATIONS: This article
      contributes by providing knowledge and insight for nurses on the roles they play
      in intensive psychiatry as stabilizers.

PMID- 24689493
TI  - Customized role play: strategy for development of psychiatric mental health nurse
      practitioner competencies.
AB  - PURPOSE: To discuss the teaching/learning strategy of customized role play to
      enhance psychiatric mental health nurse practitioner (PMHNP) students' entry
      level competency. CONCLUSIONS: Customized role play facilitates application of
      new content, understanding of the patient's experience, and assessment of skill
      deficits. PRACTICE IMPLICATIONS: New PMHNP graduates have entry level proficiency
      across the life span with a range of psychotherapeutic interventions.

PMID- 24689494
TI  - Teratogenic effects of Mimosa tenuiflora in a rat model and possible role of N
      methyl- and N,N-dimethyltryptamine.
AB  - Mimosa tenuiflora is a shrub/tree found in northeastern Brazil sometimes eaten by
      livestock and believed to be responsible for malformations observed in many
      animals from that region. The teratogenic compounds in M. tenuiflora are not
      known. This study used pregnant rats fed M. tenuiflora and components therefrom
      for bioassay and fractionation of possible teratogenic compounds. Rat pups were
      examined for cranial-facial defects and skeletal malformations. Experimental
      diets included M. tenuiflora leaf and seed material, extracts of leaf and seed,
      alkaloid extracts of leaf and seed, and N-methyltryptamine and N,N
      dimethyltryptamine. Pups from mothers who received M. tenuiflora plant material,
      methanol extracts, alkaloid extracts, and purified N-methyltryptamines had a
      higher incidence of soft tissue cleft palate and skeletal malformations. Results
      are summarized as to the frequency of observed cleft palate and other noted
      malformations for each diet versus control. 

PMID- 24689496
TI  - Synthesis and dimerization of chloro[10]cycloparaphenylene: a directly connected
      cycloparaphenylene dimer.
AB  - The first synthesis and dimerization of monochlorinated [10]cycloparaphenylene
      (chloro[10]CPP) are described. By assembling a chlorinated 1,4-diborylbenzene
      unit with brominated and borylated cis-1,4-diphenylcyclohexane units by Suzuki
      Miyaura coupling, a triangle-shaped chloro-containing macrocycle was synthesized.
      The acid-mediated "cyclohexane-to-benzene" aromatization afforded chloro[10]CPP
      without losing the chloro group. By the action of Ni(0) complex, chloro[10]CPP
      was converted to a directly connected [10]CPP dimer, which would be an ideal
      precursor for the "carbon nanobelt". 

PMID- 24689495
TI  - Up-regulation of the chemo-attractive receptor ChemR23 and occurrence of
      apoptosis in human chondrocytes isolated from fractured calcaneal osteochondral
      fragments.
AB  - To study the expression level of a panel of pro/anti-apoptotic factors and
      inflammation-related receptors in chondral fragments from patients undergoing
      surgical treatment for intra-articular calcaneal fractures, cartilage fragments
      were retrieved from calcaneal fractures of 20 patients subjected to surgical
      treatment. Primary cultures were performed using chondral fragments from
      fractured and control patients. Chondrocyte cultures from each patient of the
      fractured and control groups were subjected to immunofluorescence staining and
      quantitatively analyzed under confocal microscopy. Proteins extracted from the
      cultured chondrocytes taken from the fractured and control groups were processed
      for Western blot experiments and densitometric analysis. The percentage of
      apoptotic cells was determined using the cleaved PARP-1 antibody. The proportion
      of labelled cells was 35% for fractured specimens, compared with 7% for control
      samples. Quantification of caspase-3 active and Bcl-2 proteins in chondrocyte
      cultures showed a significant increase of the apoptotic process in fractured
      specimens compared with control ones. Fractured chondrocytes were positively
      stained for ChemR23 with statistically significant differences with respect to
      control samples. Densitometric evaluation of the immunoreactive bands confirmed
      these observations. Human articular chondrocytes obtained from patients with
      intra-articular calcaneal fractures express higher levels of pivotal pro
      apoptotic factors, and of the chemo-attractive receptor ChemR23, compared with
      control cultures. On the basis of these observations, the authors hypothesize
      that consistent prolonged chondrocyte death, associated with the persistence of
      high levels of pro-inflammatory factors, could enhance the deterioration of
      cartilage tissue with consequent development of post-traumatic arthritis
      following intra-articular bone fracture. 

PMID- 24689497
TI  - Solid-state NMR (31)P paramagnetic relaxation enhancement membrane protein
      immersion depth measurements.
AB  - Paramagnetic relaxation enhancement (PRE) is a widely used approach for measuring
      long-range distance constraints in biomolecular solution NMR spectroscopy. In
      this paper, we show that (31)P PRE solid-state NMR spectroscopy can be utilized
      to determine the immersion depth of spin-labeled membrane peptides and proteins.
      Changes in the (31)P NMR PRE times coupled with modeling studies can be used to
      describe the spin-label position/amino acid within the lipid bilayer and the
      corresponding helical tilt. This method provides valuable insight on protein
      lipid interactions and membrane protein structural topology. Solid-state (31)P
      NMR data on the 23 amino acid alpha-helical nicotinic acetylcholine receptor
      nAChR M2delta transmembrane domain model peptide followed predicted behavior of
      (31)P PRE rates of the phospholipid headgroup as the spin-label moves from the
      membrane surface toward the center of the membrane. Residue 11 showed the
      smallest changes in (31)P PRE (center of the membrane), while residue 22 shows
      the largest (31)P PRE change (near the membrane surface), when compared to the
      diamagnetic control M2delta sample. This PRE SS-NMR technique can be used as a
      molecular ruler to measure membrane immersion depth. 

PMID- 24689498
TI  - Risk assessment, genetic counseling, and clinical care for hereditary breast
      cancer.
AB  - During the last 30 years, key advances in the field of cancer genetics have
      improved identification of high-risk families in which cancer risk can be linked
      to mutations in cancer susceptible genes. Identification of individuals with
      heritable cancer risk may influence short- and long-term medical management
      issues. Heightened screening and risk reducing options can offer lifesaving
      interventions for the woman and family members who are at risk.

PMID- 24689499
TI  - A prospective cohort study to determine the relationship between serum infliximab
      concentration and efficacy in patients with luminal Crohn's disease.
AB  - BACKGROUND: Patients with Crohn's disease (CD) may experience disease relapse on
      maintenance infliximab. Anti-drug antibodies likely contribute to loss of
      response, and serum infliximab levels likely correlate with efficacy. AIM: To
      prospectively evaluate the relationship between trough serum infliximab
      concentration and disease activity. METHODS: Adult patients (N = 327) with a
      diagnosis of CD who had received at least five consecutive infliximab infusions
      and who planned to receive at least two additional infusions were enrolled. The
      Crohn's Disease Activity Index (CDAI), serum infliximab, C-reactive protein (CRP)
      and antibodies-to-infliximab (ATI) were assessed at baseline, week 4 and week 8.
      Receiver operating characteristic (ROC) analysis examined the relationship
      between infliximab concentrations and disease activity. RESULTS: The mean CDAI
      score, which decreased 1.05 points between infusions, did not correlate with the
      mean change in trough infliximab concentration (+0.39 MUg/mL; r = 0.099, P =
      0.083), but was associated with the mean change in CRP concentration (r = 0.19, P
      < 0.001). Trough infliximab concentrations below 2.8-4.6 MUg/mL best predicted a
      >= 70 point increase in the CDAI between infusions, and those below 2.7-2.8
      MUg/mL best predicted CRP >5 mg/mL at the second infusion. ATI at either visit
      decreased the proportion of patients with therapeutic infliximab trough levels
      compared with patients who were ATI negative (17.5% vs. 77.3% at visit 1 and
      13.8% vs. 75.6% at visit 3; P < 0.001 for both comparisons). CONCLUSIONS: This
      prospective study confirms the relationship between trough infliximab
      concentrations, inflammation and antibodies-to-infliximab. Infliximab trough
      concentrations below 3 MUg/mL may increase the likelihood of symptoms and
      inflammation (ClinicalTrials.gov identifier: NCT00676988).

PMID- 24689501
TI  - Mesophyll cells of C4 plants have fewer chloroplasts than those of closely
      related C3 plants.
AB  - The evolution of C(4) photosynthesis from C(3) ancestors eliminates ribulose
      bisphosphate carboxylation in the mesophyll (M) cell chloroplast while activating
      phosphoenolpyruvate (PEP) carboxylation in the cytosol. These changes may lead to
      fewer chloroplasts and different chloroplast positioning within M cells. To
      evaluate these possibilities, we compared chloroplast number, size and position
      in M cells of closely related C(3), C(3) -C(4) intermediate and C(4) species from
      12 lineages of C(4) evolution. All C(3) species had more chloroplasts per M cell
      area than their C(4) relatives in high-light growth conditions. C(3) species also
      had higher chloroplast coverage of the M cell periphery than C(4) species,
      particularly opposite intercellular air spaces. In M cells from 10 of the 12 C(4)
      lineages, a greater fraction of the chloroplast envelope was pulled away from the
      plasmalemma in the C(4) species than their C(3) relatives. C(3) -C(4)
      intermediate species generally exhibited similar patterns as their C(3)
      relatives. We interpret these results to reflect adaptive shifts that facilitate
      efficient C(4) function by enhancing diffusive access to the site of primary
      carbon fixation in the cytosol. Fewer chloroplasts in C(4) M cells would also
      reduce shading of the bundle sheath chloroplasts, which also generate energy
      required by C(4) photosynthesis.

PMID- 24689500
TI  - Third trimester-equivalent ethanol exposure does not alter complex spikes and
      climbing fiber long-term depression in cerebellar Purkinje neurons from juvenile
      rats.
AB  - BACKGROUND: Studies indicate that exposure to ethanol (EtOH) during fetal
      development damages cerebellar Purkinje cells (PCs). PC proximal dendrites
      receive glutamatergic input from climbing fibers (CFs) originating at the
      inferior olive. CF input produces a characteristic response in PCs known as the
      complex spike (CS). During the first 2 weeks of life in rodents (equivalent to
      the human third trimester of pregnancy), CF-PC synapses undergo profound
      refinement. Here, we characterized the impact of EtOH exposure during this period
      on CF-evoked responses in PCs. METHODS: Using vapor chambers, neonatal rat pups
      and their mothers were exposed to air or EtOH for 4 h/d between postnatal day 2
      (P2) and P12 (pup serum EtOH concentration, 0.16 g/dl). The function of CF-PC
      synapses was characterized using patch-clamp electrophysiological techniques in
      acute slices from the cerebellar vermis. Experiments were performed soon after
      EtOH withdrawal, when perisomatic CFs are still being eliminated (P15 to P17),
      and after weaning when CF dendritic translocation is almost complete (P21 to
      P34). RESULTS: Neither the baseline characteristics of the CS (Na(+) spike
      amplitude, area, coastline index, and afterhyperpolarization [AHP] amplitude) nor
      the type-1 metabotropic glutamate receptor (mGluR1)-mediated component of both
      the CS and AHP were significantly affected by EtOH exposure at P15 to P17 or P21
      to P34. The mGluR1-dependent long-term depression (LTD) of CF-evoked excitatory
      postsynaptic currents was not significantly affected by EtOH exposure at P21 to
      P34. CONCLUSIONS: EtOH exposure during the third trimester equivalent neither
      affected basal characteristics of the CS nor CF-LTD at rat cerebellar PCs from
      juvenile rats.

PMID- 24689503
TI  - Surface grafting of vinyl-functionalized poly(fluorene)s via thiol-ene click
      chemistry.
AB  - Thiol-ene chemistry is used for the surface grafting of vinyl-functionalized
      poly(fluorene) derivatives onto substrates containing free surface thiol groups.
      The grafting reaction proceeds in a matter of minutes under UV irradiation
      without photoinitiator, and the resulting surface-bound, solvent-impervious
      conjugated polymers retain their characteristic optoelectronic properties. End
      chain grafted poly(fluorene)s reach greater surface densities than their side
      chain grafted counterparts and show less blue-shifting of photoluminescence upon
      grafting, suggesting that chain end-grafted conjugated polymers experience less
      disruption of their extended conjugation and adopt a more brush-like surface
      conformation. Surface grafted poly(fluorene)s showed facile photopatterning, and
      thin film transistors with semiconducting polymers directly grafted to the
      dielectric layer showed performances directly comparable to conventional self
      assembled layers of performance-improving alkylsilanes. 

PMID- 24689502
TI  - Comprehensive characterization of (S)GTP-binding proteins by orthogonal
      quantitative (S)GTP-affinity profiling and (S)GTP/GTP competition assays.
AB  - Thiopurine drugs are widely used as antileukemic drugs and immunosuppressive
      agents, and 6-thioguanosine triphosphate ((S)GTP) is a major metabolite for these
      drugs. Recent studies have suggested that thiopurine drugs may exert their
      cytotoxic effects partly through binding of (S)GTP to a GTP-binding protein,
      Rac1. However, it remains unclear whether (S)GTP can also bind to other cellular
      proteins. Here, we introduced an orthogonal approach, encompassing nucleotide
      affinity profiling and nucleotide-binding competition assays, to characterize
      comprehensively (S)GTP-binding proteins along with the specific binding sites
      from the entire human proteome. With the simultaneous use of (S)GTP and GTP
      affinity probes, we identified 165 (S)GTP-binding proteins that are involved in
      several different biological processes. We also examined the binding
      selectivities of these proteins toward (S)GTP and GTP, which allowed for the
      revelation of the relative binding affinities of the two nucleotides toward the
      nucleotide-binding motif sequence of proteins. Our results suggest that (S)GTP
      mainly targets GTPases, with strong binding affinities observed for multiple
      heterotrimeric G proteins. We also demonstrated that (S)GTP binds to several
      cyclin-dependent kinases (CDKs), which may perturb the CDK-mediated
      phosphorylation and cell cycle progression. Together, this represents the first
      comprehensive characterization of (S)GTP-binding property for the entire human
      proteome. We reason that a similar strategy can be generally employed for the
      future characterization of the interaction of other modified nucleotides with the
      global proteome. 

PMID- 24689504
TI  - Febrile pleuropericarditis, a potentially life-threatening adverse event of
      balsalazide--case report and literature review of the side effects of 5
      aminosalicylates.
AB  - Ulcerative colitis (UC) is an idiopathic chronic inflammatory disorder that
      affects the colonic mucosa. One class among the drugs used for its treatment is
      the 5-aminosalicylates (5-ASAs). While highly efficacious in treating mild-to
      moderate UC, 5-ASAs are associated with rare but potentially life-threatening
      side effects such as pericarditis, myocarditis and pneumonitis. These adverse
      events appear to be caused by a hypersensitivity reaction and resolve after
      cessation of 5-ASA drugs. This article presents a case report of febrile
      pleuropericarditis in a UC patient treated with balsalazide, and provides a
      thorough literature review of the rare side effects of 5-ASAs, their incidence,
      clinical presentation, differential diagnosis and treatment. In conclusion, the
      clinicians should be aware that this type of adverse events to 5-ASA compounds
      can be easily overlooked but it has significant morbidity if not promptly
      diagnosed.

PMID- 24689505
TI  - Manic psychosis associated with ginseng: a report of two cases and discussion of
      the literature.
AB  - BACKGROUND: Herbal medicine use, highly prevalent in the general population, is
      often a neglected component of the medical history. Herbs are presumed safe
      because they are "natural" self-care products. We call attention to the following
      issues: Panax ginseng, one of the most frequently used herbal medicines, has
      complex pharmacological activity, and can be associated with severe psychiatric
      symptoms. Physicians may be unfamiliar with herbal therapy risks, and the need
      for further education and systematic research is highlighted. OBJECTIVE: To
      describe two cases of new onset manic psychoses associated with high dose,
      chronic ginseng use, and review the relevant literature. CASE REPORTS: A 23-year
      old man developed acute mania after one month of daily ginseng use and
      intermittent cannabis use. A 79-year-old man developed hypomania while using
      ginseng and yohimbine for erectile dysfunction, and had a recurrence of mania
      after stopping yohimbine but increasing his daily intake of ginseng.
      CONCLUSIONS/SUMMARY: Symptoms of mania fully remitted within days upon
      discontinuation of ginseng and supportive treatment. Available data prevent a
      clear determination of causation; however, ginseng-induced mania in the these and
      previous case reports is suggested by the following: patients had no prior
      psychiatric history, daily use of ginseng was temporally associated with mania
      onset, patients ingested much higher doses for a longer duration than recommended
      in Traditional Chinese Medicine (TCM), and withdrawal of ginseng led to rapid
      remission. Generally well tolerated, many physicians are unaware that ginseng may
      be associated with acute and significant psychiatric disturbances for certain at
      risk individuals.

PMID- 24689506
TI  - In the footsteps of Wilcock, Part one: The evolution of doing, being, becoming,
      and belonging.
AB  - This article will present a critical analysis of the four dimensions of
      occupation, doing, being, becoming and belonging, and propose clearer
      understandings of the terms. The concepts have developed and evolved since
      Wilcock first introduced them as main constructs of Occupational Perspective of
      Health (OPH), with doing and being receiving the most comprehensive development.
      However, the concepts of becoming and belonging remain underdeveloped. Given the
      complex nature of occupation, this comprehensive analysis of each dimension adds
      greater depth to our understanding, and provisional definitions of each term are
      provided to guide their ongoing development.

PMID- 24689507
TI  - Palladium-catalyzed cross-coupling reactions of arylsiloxanes with aryl halides:
      application to solid-supported organic synthesis.
AB  - The solid-phase version of the Pd-catalyzed Hiyama reaction between a variety of
      aryltriethoxysilanes and immobilized aryl halides was developed. Smooth cross
      coupling was achieved to afford the corresponding biaryl products in moderate to
      excellent yields. The described protocol would be particularly useful for the
      construction of 4'-substituted 1,1'-biphenyl derivatives. 

PMID- 24689508
TI  - One-step synthesis of betalains using a novel betalamic acid derivatized support.
AB  - Betalains are plant pigments with high antioxidant and cancer chemopreventive
      properties used by the food industry as safe colorants. Betalains are restricted
      to species of the order Caryophyllales, and difficulty in obtaining individual
      molecules has limited their structural identification and application. This study
      was designed to develop a betalamic acid derivatized support generated from a
      primary amine polymer. The novel material presents color properties of a
      pseudobetaxanthin, and it is stable for at least 6 months. The bond formed can be
      displaced at mild conditions by the addition of amines in aqueous solutions over
      a broad pH range and at 25  degrees C. This releases the betalamic acid while
      forming the corresponding pigment. This one-step procedure significantly
      simplifies the process of obtaining semisynthetic betalains, and it is optimized
      here for the formation of betaxanthins and betacyanins derived from tyramine,
      dopamine, pyrrolidine, and indoline. The new method makes access to single
      betalains available to the entire scientific community and could stimulate
      research and applications in the field. 

PMID- 24689509
TI  - Unemployment as a risk factor for completed suicide: a psychological autopsy
      study.
AB  - This study adopts a psychological autopsy method to compare (1) unemployed
      suicides, (2) other suicides who were either employed or not in the labor force,
      and (3) psychiatric outpatients without any prior suicidal behavior. A total of
      245 consecutive suicides from Province of Parma (Italy) with recorded employment
      status were included in the analysis. The control group included 41 psychiatric
      outpatients aged 18 to 64 years, who had not engaged in any previous suicidal
      act, and who were unemployed. The unemployed suicides had a risk 17 times higher
      to have had financial problems in the last 12 months (95% confidence interval
      [CI]: 2.0/149.5; p < 0.01) than other suicides. Unemployed suicides (compared to
      living unemployed controls) were 10 times more likely to have had poor social
      support (95% CI: 1.7/56.1; p < 0.01), 16 times more likely to have had any
      stressful life events in the past 12 months (95% CI: 2.5/103.9; p < 0.01), and 22
      times more likely to have a diagnosis of borderline personality disorder (95% CI:
      2.4/203.2; p < 0.01). New suicide prevention strategies for those who are facing
      job loss need to focus on social support and personality disorders, as well as
      hopelessness and despair. 

PMID- 24689510
TI  - Association of the IL-10 receptor A536G (S138G) loss-of-function variant with
      recurrent miscarriage.
AB  - PROBLEM: We investigated the association of interleukin-10 receptor (IL10R1) loss
      of-function variant A536G/S138G with recurrent pregnancy loss (RPL). METHOD OF
      STUDY: Study subjects comprised 300 women with >=3 miscarriages, and 350 control
      women. RESULTS: Significantly higher 536G-allele frequency was seen in RPL cases,
      thus assigning pathogenic role for this allele. Significant difference in
      A536G/S138G genotypes distribution was seen between RPL cases and controls,
      evidenced by enrichment of 536A/G and 536G/G genotypes in RPL cases. Setting A/A
      genotype as reference (OR = 1.00), increased RPL risk was seen with 536A/G, and
      more in 536G/G carriers, thereby establishing dose-dependency. CONCLUSION: IL10R1
      loss-of-function A536/S138G polymorphism may contribute to RPL pathogenesis.

PMID- 24689511
TI  - Novel gene mutations and clinical features in patients with pantothenate kinase
      associated neurodegeneration.

PMID- 24689512
TI  - Microencapsulation of hydrophobic liquids in closed all-silica colloidosomes.
AB  - A facile approach for the microencapsulation of hydrophobic liquids in closed
      solid all-silica colloidosomes is reported. The method is based on the formation
      of oil-in-water emulsions stabilized by silica nanoparticles and subsequent
      gluing of the particles at the water/oil interface by a silica precursor polymer
      hyperbranched polyethoxysiloxane. By this means different oils are successfully
      enclosed in hence formed all-silica colloidosomes with almost 100% efficiency.
      Via a systematical study it is demonstrated that this process is a delicate
      interplay between the emulsion stability, oil polarity, and sol-gel reaction
      kinetics. This approach allows fabricating microcapsules of hydrophobic liquid
      substances in a mechanically stable, chemically inert, and biocompatible matrix,
      silica, with high encapsulation capacity and a controlled release profile. 

PMID- 24689513
TI  - Microstructural changes in cartilage and bone related to repetitive overloading
      in an equine athlete model.
AB  - The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is
      known to be subjected to repetitive overloading that can lead to the accumulation
      of joint tissue damage, degeneration, and stress fractures, some of which result
      in catastrophic failure. However, there is still a need to understand at a
      detailed microstructural level how this damage progresses in the context of the
      wider joint tissue complex, i.e. the articular surface, the hyaline and calcified
      cartilage, and the subchondral bone. MC3 bones from non-fractured joints were
      obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age
      between 3 and 8 years, with documented histories of active race training.
      Detailed microstructural analysis of two clinically important sites, the
      parasagittal grooves and the mid-condylar regions, identified extensive levels of
      microdamage in the calcified cartilage and subchondral bone concealed beneath
      outwardly intact hyaline cartilage. The study shows a progression in microdamage
      severity, commencing with mild hard-tissue microcracking in younger animals and
      escalating to severe subchondral bone collapse and lesion formation in the
      hyaline cartilage with increasing age and thus athletic activity. The presence of
      a clearly distinguishable fibrous tissue layer at the articular surface
      immediately above sites of severe subchondral collapse suggested a limited
      reparative response in the hyaline cartilage.

PMID- 24689514
TI  - Gluteal and abdominal subcutaneous adipose tissue depots as stroma cell source:
      gluteal cells display increased adipogenic and osteogenic differentiation
      potentials.
AB  - Human adipose-derived stroma cells (ADSCs) have successfully been employed in
      explorative therapeutic studies. Current evidence suggests that ADSCs are
      unevenly distributed in subcutaneous adipose tissue; therefore, the anatomical
      origin of ADSCs may influence clinical outcomes. This study was designed to
      investigate proliferation and differentiation capacities of ADSCs from the
      gluteal and abdominal depot of 8 females. All had normal BMI (22.01 +/- 0.39
      kg/m(2) ) and waist circumference (81.13 +/- 2.33 cm). Examination by physicians
      and analysis of 31 laboratory parameters did not reveal possibly confounding
      medical disorders. Gluteal and abdominal adipose tissue was sampled by en bloc
      resection on day 7 (+/-1) after the last menses. Histological examination did not
      reveal significant depot-specific differences. As assessed by BrdU assay,
      proliferation of cells from both depots was similar after 24 h and analysis of 15
      cell surface markers by flow cytometry identified the isolated cells as ADSCs,
      again without depot-specific differences. ADSCs from both depots differentiated
      poorly to chondroblasts. Gluteal ADSCs displayed significantly higher adipogenic
      differentiation potential than abdominal cells. Osteogenic differentiation was
      most pronounced in gluteal cells, whereas differentiation of abdominal ADSCs was
      severely impaired. Our data demonstrate a depot-specific difference in ADSC
      differentiation potential with abdominal cells failing to meet the criteria of
      multipotent ADSCs. This finding should be taken into account in future
      explorations of ADSC-derived therapeutic strategies.

PMID- 24689515
TI  - Population pharmacokinetic modelling to assess clinical drug-drug interaction
      between AZD7325 and midazolam.
AB  - WHAT IS KNOWN AND OBJECTIVE: AZD7325 is a selective gamma-amino-butyric acid
      (GABAA )alpha2, 3 receptor modulator. The aims of this analysis were to develop
      population pharmacokinetic (PPK) models of AZD7325 and midazolam and to assess
      the induction effect of AZD7325 on CYP3A4 with midazolam as a substrate. METHODS:
      Drug-drug interaction data of AZD7325 and midazolam from 24 healthy subjects were
      available for model development. PPK models were developed in a sequential manner
      using NONMEM. Both AZD7325 and midazolam pharmacokinetics were described by two
      compartment models, and a transit compartment absorption model and a first-order
      absorption model were applied for the absorption of AZD7325 and midazolam,
      respectively. The induction of CYP3A by AZD7325 was described by a transit enzyme
      model, where the elimination of midazolam was proportionally linked to the enzyme
      amount. Simulations were performed to predict dosing regimens to account for the
      induction of CYP3A4. RESULTS AND DISCUSSION: The population estimates for AZD7325
      clearance, intercompartmental clearance, central and peripheral volume were 36,
      29.2 L/h, 169 and 392 L, respectively, with interindividual variability (IIV) of
      35% and 24% for clearance and central volume. Midazolam clearance,
      intercompartmental clearance, central and peripheral volume were estimated to be
      62.7, 34.7 L/h, 133 and 146 L, respectively, with 43% IIV for clearance. The
      estimated mean transit time for induction of the CYP3A4 enzyme was 197 h, with
      57% IIV. WHAT IS NEW AND CONCLUSION: The PPK models developed adequately
      described the clinical observation of AZD7325-mediated CYP3A4 enzyme induction
      with midazolam as a probe. The model could provide basis for the rational dosing
      of AZD7325 in clinical practice.

PMID- 24689516
TI  - What you should know about omega-3 fatty acids and prostate cancer.

PMID- 24689517
TI  - Ion-gated synthetic photosystems.
AB  - Herein, molecular strings of ions built along charge-transporting channels are
      shown to dramatically increase photocurrents and enable charge transport over
      long distances, thus confirming the existence and significance of ion-gated
      photosystems. For their synthesis, ordered and oriented stacks of
      naphthalenediimides were grown on indium tin oxide by ring-opening disulfide
      exchange polymerization. To these charge-transporting channels, coaxial strings
      of anions or cations-fixed, mobile, complete, partial, pure, or mixed-were added
      by orthogonal hydrazone exchange. The presence of partially protonated
      carboxylates was found to most significantly increase activity, implying that
      they both attract holes and repel electrons, that is, facilitate photoinduced
      charge separation and hinder charge recombination at the same time. As a result
      of this quite remarkable situation, photocurrents increased rather than decreased
      with increasing charge stabilization on their "stepping stones." The presence of
      mobile anions facilitated long-distance charge transport through thick films.
      Turned off by inhibited anion mobility, that is, proton hopping, hole/proton
      antiport is identified to account for long-distance charge transport in ion-gated
      photosystems. 

PMID- 24689518
TI  - Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for
      a neuroinflammatory model of chronic alcoholism.
AB  - BACKGROUND: Liver inflammation in alcoholism has been hypothesized to influence
      the development of a neuroinflammatory process in the brain characterized by
      neurodegeneration and altered cognitive function. Monocyte chemoattractant
      protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) elevations have been noted
      in the alcoholic brain at autopsy and may have a role in this process. METHODS:
      We studied cerebrospinal fluid (CSF) levels of MCP-1 as well as interleukin-1beta
      and tumor necrosis factor-alpha in 13 healthy volunteers and 28 alcoholics during
      weeks 1 and 4 following detoxification. Serum liver enzymes were obtained as
      markers of alcohol-related liver inflammation. RESULTS: Compared to healthy
      volunteers, MCP-1 levels were significantly higher in alcoholics both on day 4
      and day 25 (p < 0.0001). Using multiple regression analysis, we found that MCP-1
      concentrations were positively associated with the liver enzymes gamma
      glutamyltransferase (GGT; p = 0.03) and aspartate aminotransferase/glutamic
      oxaloacetic transaminase (AST/GOT; p = 0.004). CONCLUSIONS: These preliminary
      findings are consistent with the hypothesis that neuroinflammation as indexed by
      CSF MCP-1 is associated with alcohol-induced liver inflammation, as defined by
      peripheral concentrations of GGT and AST/GOT.

PMID- 24689519
TI  - Fragmentation of integral membrane proteins in the gas phase.
AB  - Integral membrane proteins (IMPs) are of great biophysical and clinical interest
      because of the key role they play in many cellular processes. Here, a
      comprehensive top down study of 152 IMPs and 277 soluble proteins from human
      H1299 cells including 11 087 fragments obtained from collisionally activated
      dissociation (CAD), 6452 from higher-energy collisional dissociation (HCD), and
      2981 from electron transfer dissociation (ETD) shows their great utility and
      complementarity for the identification and characterization of IMPs. A central
      finding is that ETD is ~2-fold more likely to cleave in soluble regions than
      threshold fragmentation methods, whereas the reverse is observed in transmembrane
      domains with an observed ~4-fold bias toward CAD and HCD. The location of charges
      just prior to dissociation is consistent with this directed fragmentation:
      protons remain localized on basic residues during ETD but easily mobilize along
      the backbone during collisional activation. The fragmentation driven by these
      protons, which is most often observed in transmembrane domains, both is of higher
      yield and occurs over a greater number of backbone cleavage sites. Further, while
      threshold dissociation events in transmembrane domains are on average 10.1 (CAD)
      and 9.2 (HCD) residues distant from the nearest charge site (R, K, H, N
      terminus), fragmentation is strongly influenced by the N- or C-terminal position
      relative to that site: the ratio of observed b- to y-fragments is ~1:3 if the
      cleavage occurs >7 residues N-terminal and ~3:1 if it occurs >7 residues C
      terminal to the nearest basic site. Threshold dissociation products driven by a
      mobilized proton appear to be strongly dependent on not only relative position of
      a charge site but also N- or C-terminal directionality of proton movement. 

PMID- 24689520
TI  - Naphthoquinone spiroketals and organic extracts from the endophytic fungus Edenia
      gomezpompae as potential herbicides.
AB  - From the fermentation mycelium of the endophytic fungus Edenia gomezpompae were
      obtained several phytotoxic compounds including two new members of the
      naphthoquinone spiroketal family, namely, palmarumycin EG1 (1) and preussomerin
      EG4 (4). In addition, preussomerins EG1-EG3 (7-9) and palmarumycins CP19 (2),
      CP17 (3), and CP2 (6), as well as ergosta-4,6,8(14),22-tetraen-3-one (5), were
      obtained. Compounds 2, 3, and 5 are new to this species. The structures of
      palmarumycins CP19 (2) and CP17 (3) were unambiguously determined by X-ray
      analysis. The isolates and mycelium organic extracts from four morphological
      variants of E. gomezpompae caused significant inhibition of seed germination,
      root elongation, and seedling respiration of Amaranthus hypochondriacus, Solanum
      lycopersicum, and Echinochloa crus-galli. The treatments also affected
      respiration on intact mitochondria isolated from spinach. 

PMID- 24689521
TI  - N-bromosuccinimide-induced aminocyclization-aziridine ring-expansion cascade: an
      asymmetric and highly stereoselective approach toward the synthesis of azepane.
AB  - A novel N-bromosuccinimide induced aminocyclization-aziridine ring expansion
      cascade is reported. Substituted azepanes were isolated exclusively in good
      yields. The azepane products could be transformed into a number of functional
      molecules including piperidines, a bicyclic amine, and a bridgehead amide. 

PMID- 24689522
TI  - Paraneoplastic cerebellar degeneration as the first evidence of malignancy: a
      case report.
AB  - Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated paraneoplastic
      disorder affecting the cerebellum. PCD associated with ovarian malignancy is a
      rare occurrence with fewer than 100 cases reported in published work. PCD
      patients express anti-Yo antibody, one of the anti-onconeuronal antibodies which
      is most likely associated with gynecologic or breast malignancies. In this
      report, we present the case of a 65-year-old postmenopausal woman presenting with
      acute symptoms of PCD as a first sign of ovarian malignancy. 

PMID- 24689526
TI  - A survey on oral care practices for ventilator-assisted patients in intensive
      care units in 3A hospitals of mainland China.
AB  - Oral hygiene is a critical element of patient care, particularly among patients
      who need ventilator-assisted equipment. The objective of this study was to
      explore the current status of oral care practices, attitudes, education and
      knowledge among intensive care unit (ICU) nurses caring for ventilator-assisted
      patients in 3A hospitals in mainland China. To achieve this aim, an 18-item self
      assessment questionnaire was mailed to head ICU nurses in 189 Grade 3A hospitals.
      Additional data were collected through in-person interviews at 38 ICUs throughout
      Sichuan, Shanxi, Jiangsu provinces, as well as Chongqing and Beijing. We found
      that most ICUs conducted oral examinations at patient admission, and that this
      care was largely provided by nurses. The most common oral care methods were foam
      swabs and mouth rinse containing antibiotics or disinfectants. Although the
      majority of ICUs provided continuing training for oral care, and most training
      was conducted by head nurses, the content and scope of training were not
      consistent among the hospitals in the study. The most popular sources of oral
      care knowledge were academic journals, Internet and professional books. Overall,
      it is clear that an evidence-based oral care standard manual is urgently needed
      for oral practice in ICUs in mainland China. 

PMID- 24689527
TI  - Metabolic and transcript analysis of the flavonoid pathway in diseased and
      recovered Nebbiolo and Barbera grapevines (Vitis vinifera L.) following infection
      by Flavescence doree phytoplasma.
AB  - Flavescence doree phytoplasma (FDp) infections seriously affect production and
      survival of grapevine. We analysed the changes in the flavonoid pathway occurring
      in two red cultivars, the highly susceptible Barbera and the less susceptible
      Nebbiolo, following FDp infection. A combination of metabolic and transcript
      analyses was used to quantify flavonoid compounds and expression of a set of
      genes involved in their biosynthesis. Quantification of anthocyanins, flavonols,
      proanthocyanidins and related biosynthetic enzymes was performed over the
      vegetative season, at four time points, on healthy, infected and recovered
      plants. A strong activation of anthocyanin accumulation was observed in infected
      Barbera leaves, while the response was less marked in Nebbiolo. Proanthocyanidins
      also accumulated mainly in infected Barbera leaves, even if basal
      proanthocyanidin concentration was higher in healthy and recovered Nebbiolo.
      Biochemical data were supported by transcript analysis: genes of the stem
      flavonoid pathway and of the anthocyanin and proanthocyanidin branches were
      expressed at a higher level in infected than in healthy plants, with a different
      magnitude between the two cultivars. Based on our results, we hypothesize that
      flavonoid accumulation is a physiological consequence of FD infection without
      affecting phytoplasma multiplication, although proanthocyanidin accumulation
      could help repel further infection by the insect vector. 

PMID- 24689528
TI  - Breaking the mould - novel diagnostic and therapeutic strategies for invasive
      pulmonary aspergillosis in the immune deficient patient.
AB  - Invasive pulmonary aspergillosis (IPA) caused by the ubiquitous environmental
      fungus Aspergillus is a frequently fatal lung disease of immunocompromised humans
      accounting for more than 200,000 infections each year, with an associated
      mortality rate of 30-90%. This review addresses the current status of IPA
      diagnosis and treatment and the urgent need to develop accurate, non-invasive
      strategies for identifying pulmonary infections in the ever-expanding population
      of immune deficient patients at risk of acquiring opportunistic fungal infections
      including hematological malignancy and hematopoetic stem cell transplant
      patients. Recent advances in the use of an Aspergillus-specific monoclonal
      antibody, JF5, for point-of-care diagnosis of IPA using lateral-flow technology
      is examined, as is its use in PET/MRI bioimaging and radio-immunotherapy using
      radionuclide-labeled single chain antibody fragments, Fab fragments, and a fully
      humanized JF5 derivative.

PMID- 24689529
TI  - The promise and limitations of TNF-alpha inhibition for uveitis.

PMID- 24689530
TI  - Consonant production and intelligibility in cri du chat syndrome.
AB  - This article focuses on consonant productions by a group of children with cri du
      chat syndrome (CdCS) and examines how various aspects of these productions
      contribute to these children's overall intelligibility. Eight children and
      adolescents with CdCS participated in the study, and the following four questions
      were addressed: (1) What are the characteristic features of the consonant
      inventories of the subjects in terms of size and types of consonants; (2) how do
      the subjects render the consonant phonemes of the target language; (3) to what
      degree do the subjects produce target-like words; and (4) what is the
      relationship between consonant production and intelligibility? For the majority
      of our subjects, we found low proportions of correctly produced consonants, small
      consonant inventories with several recurrent types of deviant consonants,
      inaccuracy in realization of target phonemes and variable similarity to target
      words, all of which may contribute to reduced intelligibility.

PMID- 24689531
TI  - Proton conduction in water ices under an electric field.
AB  - We report on a first-principles study of the effects produced by a static
      electric field on proton conduction in ordinary hexagonal ice (phase Ih) and in
      its proton-ordered counterpart (phase XI). We performed ab initio molecular
      dynamics simulations of both phases and investigated the effects produced by the
      field on the structure of the material, with particular attention paid to the
      phenomenon of proton transfer. We observed that in ice Ih molecules start to
      dissociate for field intensities around 0.25 V/A, as in liquid water, whereas
      fields stronger than 0.36 V/A are needed to induce a permanent proton flow. In
      contrast, in ice XI, electric fields as intense as 0.22 V/A are already able to
      induce and sustain, through correlated proton jumps, an ionic current; this
      behavior suggests, somewhat counterintuitively, that the ordering of protons
      favors the autoprotolysis phenomenon. However, the same is not true for static
      conductivities. In fact, both crystalline phases show an ohmic behavior in the
      conduction regime, but the conductivity of ice Ih turns out to be larger than
      that of ice XI. We finally discuss the qualitative and quantitative importance of
      the conspicuous concentration of ionic defects generated by intense electric
      fields in determining the value of the conductivity, also through a comparison
      with the experimental data available for saline ices. 

PMID- 24689532
TI  - Serological survey of rodent-borne viruses in Finnish field voles.
AB  - In northern Europe, rodent populations display cyclic density fluctuations that
      can be correlated with the human incidence of zoonotic diseases they spread.
      During density peaks, field voles (Microtus agrestis) become one of the most
      abundant rodent species in northern Europe, yet little is known of the viruses
      they host. We screened 709 field voles, trapped from 14 sites over 3 years, for
      antibodies against four rodent-borne, potentially zoonotic viruses or virus
      groups-hantaviruses, lymphocytic choriomeningitis virus (LCMV), Ljungan virus
      (LV), and orthopoxviruses (OPV). Antibodies against all four viruses were
      detected. However, seroprevalence of hantaviruses, LV, and LCMV was low. OPV
      antibodies (most likely cowpox) were more common but restricted geographically to
      southeastern Finland. Within these sites, antibody prevalence showed delayed
      density dependence in spring and direct density dependence in fall. Higher
      seroprevalence was found in spring than fall. These results substantially
      increase knowledge of the presence and distribution of viruses of field voles in
      Finland, as well as CPXV infection dynamics.

PMID- 24689533
TI  - Proinflammatory-activated glioma cells induce a switch in microglial polarization
      and activation status, from a predominant M2b phenotype to a mixture of M1 and
      M2a/B polarized cells.
AB  - Malignant gliomas are primary brain tumors characterized by morphological and
      genetic complexities, as well as diffuse infiltration into normal brain
      parenchyma. Within gliomas, microglia/macrophages represent the largest tumor
      infiltrating cell population, contributing by at least one-third to the total
      tumor mass. Bi-directional interactions between glioma cells and microglia may
      therefore play an important role on tumor growth and biology. In the present
      study, we have characterized the influence of glioma-soluble factors on
      microglial function, comparing the effects of media harvested under basal
      conditions with those of media obtained after inducing a pro-inflammatory
      activation state in glioma cells. We found that microglial cells undergo a
      different pattern of activation depending on the stimulus; in the presence of
      activated glioma-derived factors, i.e. a condition mimicking the late stage of
      pathology, microglia presents as a mixture of polarization phenotypes (M1 and
      M2a/b), with up-regulation of iNOS (inducible nitric oxide synthase), ARG
      (arginase) and IL (interleukine)-10. At variance, microglia exposed to basal
      glioma-derived factors, i.e. a condition resembling the early stage of pathology,
      shows a more specific pattern of activation, with increased M2b polarization
      status and up-regulation of IL-10 only. As far as viability and cell
      proliferation are concerned, both LI-CM [LPS (lipopolysaccharide)-IFNgamma
      (interferon gamma) conditioned media] and C-CM (control-conditioned media) induce
      similar effects on microglial morphology. Finally, in human glioma tissue
      obtained from surgical resection of patients with IV grade glioblastoma, we
      detected a significant amount of CD68 positive cells, which is a marker of
      macrophage/microglial phagocytic activity, suggesting that in vitro findings
      presented here might have a relevance in the human pathology as well.

PMID- 24689534
TI  - Simple way to engineer metal-semiconductor interface for enhanced performance of
      perovskite organic lead iodide solar cells.
AB  - A thin wide band gap organic semiconductor N,N,N',N'-tetraphenyl-benzidine layer
      has been introduced by spin-coating to engineer the metal-semiconductor interface
      in the hole-conductor-free perovskite solar cells. The average cell power
      conversion efficiency (PCE) has been enhanced from 5.26% to 6.26% after the
      modification and a highest PCE of 6.71% has been achieved. By the aid of
      electrochemical impedance spectroscopy and dark current analysis, it is revealed
      that this modification can increase interfacial resistance of CH3NH3PbI3/Au
      interface and retard electron recombination process in the metal-semiconductor
      interface.